PMID- 26350790 TI - Circumcision Status and Time to Sexual Debut Among Youth in Sub-Saharan Africa: Evidence from Six Demographic and Health Surveys. AB - This paper examines the relationship between circumcision status and timing of sexual debut among unmarried youth in Sub-Saharan Africa using Demographic and Health Surveys. Results from survival analysis indicate that the association between circumcision and timing of first sex is place and context specific. Compared to uncircumcised, circumcised men in Rwanda, Uganda and Namibia hasten sexual initiation, whilst circumcised youth in Ethiopia and Mali delayed sex initiation. In Togo however, we found parity in timing to sexual debut. Our multivariate results reveal that, knowledge of HIV/AIDS risk and educational level also feed into the association between circumcision and timing of sex initiation- implying that efforts to prevent new HIV infection through circumcision could benefit from a proper understanding of how diverse set of factors interact in specific contexts to shape youth's decisions to initiate early sex. PMID- 26350791 TI - Dissolved organic matter in Lake Superior: insights into the effects of extraction methods on chemical composition. AB - Dissolved organic matter (DOM) in aquatic systems plays many biogeochemical roles, acting as a sunscreen, a food source, a trace metal chelator, and a photosensitizer. The efficiency of DOM in these roles is, in part, a function of its composition, which is difficult to determine due to its heterogeneity and the difficulty in isolating representative portions for subsequent molecular level analyses. In this study, the performance of two major types of solid phase extraction (SPE) resins (C18 vs. polymeric SDVB) in disk format (C18 disk vs. SDB XC disk) was studied using DOM from Lake Superior, the earth's largest lake by area. The performance of the two SPE disks and their influences on the molecular chemical composition of the extracted retentates were studied with UV-vis spectrometry and negative-ion electrospray Fourier transform ion cyclotron resonance mass spectrometry (ESI FT-ICR MS). We found that SDB-XC disks outperformed C18 disks in the isolation of DOM in terms of both higher recovery and less fractionation relative to the initial DOM composition. Extracts of the same samples obtained with the different resins shared 70% of molecular formulae. Compounds exclusive to the SDB-XC extractions exhibited similar compound distributions to those of the shared formulae but were enriched in N, P, and S and more aromatic. The C18 exclusive compounds had somewhat higher H/C ratios and contained a large proportion of compounds with oxygen and nitrogen (CHON). Cluster analysis and principle component analysis confirmed that sample location was the main driver of the composition of extracted samples but showed some fractionation of the samples based upon the type of resin. PMID- 26350792 TI - Patient and Physician Perspectives on MSdialog, an Electronic PRO Diary in Multiple Sclerosis. AB - BACKGROUND: MSdialog, a web- and mobile-based software application, captures data on self-administration of subcutaneous interferon beta-1a, clinical outcomes, and patient-reported outcomes in patients with multiple sclerosis outside the clinic. METHODS: Patient and healthcare professional reactions to MSdialog were surveyed; participants rated benefits of MSdialog detailed in an explanatory video. A 6 week pilot study of patients with multiple sclerosis then assessed MSdialog usability. After participating in a training teleconference, patients completed weekly health reports via MSdialog, plus two usability surveys (weeks 3 and 6) and an exploratory follow-up telephone interview. RESULTS: Seventy-six patients, 92 neurologists and 40 multiple sclerosis nurses completed the MSdialog benefits survey. Highly motivating benefits for patients included sharing information with healthcare providers and capturing patient-reported outcomes data; healthcare providers were highly motivated by data availability on patient-reported outcomes and adherence. Thirty-nine of 42 enrolled patients completed the pilot study. Overall, 87% of patients stated that completion of patient-reported outcomes with MSdialog fitted in "fairly well" to "extremely well" with their weekly routine. At week 6, 77% of patients were "very satisfied" or "extremely satisfied" with their MSdialog experience; 82% considered it better than previous methods for tracking their health and 95% would recommend using MSdialog. Most patients were highly motivated to use MSdialog; reasons given included "helps me remember what to mention to my doctor". CONCLUSION: MSdialog was considered easy to use and superior to patients' previous methods for tracking health. The ability to provide valuable data to healthcare providers offers the potential to improve patient-physician communication and engagement. PMID- 26350793 TI - Quantitative Analysis of Formaldehyde-induced Fluorescence in Paraffin-embedded Specimens of Malignant Melanomas and Other Melanocytic Lesions. AB - Inter-observer agreement is problematic in the histopathological diagnosis of melanoma and melanocytic naevi, even among expert pathologists. Formaldehyde induced fluorescence (FIF) has been used for histochemical demonstration of catecholamines, 5-hydroxytryptamine and their immediate precursors. FIF can detect melanogenic activity and may be useful in differentiating malignant melanoma from other melanocytic lesions. The fluorescence of various types of melanocytic lesions has been previously studied quantitatively in formalin-fixed and paraffin-embedded sections. This study compared 2 sets of excitation and emission bands: 450-490 nm excitation/510-560 nm absorption filters (filter unit A) and 480 nm excitation/510< nm absorption filters (filter unit B). Higher FIF was observed with filter unit A than with filter unit B. FIF intensity of central regions was found to be higher than that of the peripheral regions. Mean FIF was significantly higher in malignant melanomas than in naevi. Fluorescence imaging with filter unit A gave better diagnostic performance. In conclusion, quantitative measurement of FIF is a useful marker of malignant potential. PMID- 26350794 TI - Spatio-temporal assessment of soil erosion risk in different agricultural zones of the Inle Lake region, southern Shan State, Myanmar. AB - Myanmar is one of Southeast Asia's climatically most diverse countries, where sheet, rill, and gully erosion affect crop yields and subsequently livelihood strategies of many people. In the unique wetland ecosystem of Inle Lake, soil erosion in surrounding uplands lead to sedimentation and pollution of the water body. The current study uses the Revised Universal Soil Loss Equation (RUSLE) to identify soil erosion risks of the Inle Lake region in space and time and to assess the relationship between soil erosion and degradation for different agricultural zones and cropping systems. Altogether, 85% of soil losses occurred on barren land along the steep slopes. The hotspot of soil erosion risk is situated in the western uplands characterized by unsustainable land use practices combined with a steep topography. The estimated average soil losses amounted to 19.9, 10.1, and 26.2 t ha(-1) yr(-1) in 1989, 2000, and 2009, respectively. These fluctuations were mainly the results of changes in precipitation and land cover (deforestation (-19%) and expansion of annual cropland (+35%) from 1989 to 2009). Most farmers in the study area have not yet adopted effective soil protection measures to mitigate the effects of soil erosion such as land degradation and water pollution of the lake reservoir. This urgently needs to be addressed by policy makers and extension services. PMID- 26350795 TI - Geospatial monitoring and prioritization of forest fire incidences in Andhra Pradesh, India. AB - Forest fire has been identified as one of the key environmental issue for long term conservation of biodiversity and has impact on global climate. Spatially multiple observations are necessary for monitoring of forest fires in tropics for understanding conservation efficacy and sustaining biodiversity in protected areas. The present work was carried out to estimate the spatial extent of forest burnt areas and fire frequency using Resourcesat Advanced Wide Field Sensor (AWiFS) data (2009, 2010, 2012, 2013 and 2014) in Andhra Pradesh, India. The spatio-temporal analysis shows that an area of 7514.10 km(2) (29.22% of total forest cover) has been affected by forest fires. Six major forest types are distributed in Andhra Pradesh, i.e. semi-evergreen, moist deciduous, dry deciduous, dry evergreen, thorn and mangroves. Of the total forest burnt area, dry deciduous forests account for >75%. District-wise analysis shows that Kurnool, Prakasam and Cuddapah have shown >100 km(2) of burnt area every year. The total forest burnt area estimate covering protected areas ranges between 6.9 and 22.3% during the study period. Spatial burnt area analysis for protected areas in 2014 indicates 37.2% of fire incidences in the Nagarjunasagar Srisailam Tiger Reserve followed by 20.2 % in the Sri Lankamalleswara Wildlife Sanctuary, 20.1% in the Sri Venkateswara Wildlife Sanctuary and 17.4% in the Gundla Brahmeswaram Wildlife Sanctuary. The analysis of cumulative fire occurrences from 2009 to 2014 has helped in delineation of conservation priority hotspots using a spatial grid cell approach. Conservation priority hotspots I and II are distributed in major parts of study area including protected areas of the Nagarjunasagar Srisailam Tiger Reserve and Gundla Brahmeswaram Wildlife Sanctuary. The spatial database generated will be useful in studies related to influence of fires on species adaptability, ecological damage assessment and conservation planning. PMID- 26350796 TI - Optimal performance of networked control systems with bandwidth and coding constraints. AB - The optimal tracking performance of multiple-input multiple-output (MIMO) discrete-time networked control systems with bandwidth and coding constraints is studied in this paper. The optimal tracking performance of networked control system is obtained by using spectral factorization technique and partial fraction. The obtained results demonstrate that the optimal performance is influenced by the directions and locations of the nonminimum phase zeros and unstable poles of the given plant. In addition to that, the characters of the reference signal, encoding, the bandwidth and additive white Gaussian noise (AWGN) of the communication channel are also closely influenced by the optimal tracking performance. Some typical examples are given to illustrate the theoretical results. PMID- 26350797 TI - The lifetime risk of pneumonia in patients with neuromuscular scoliosis at a mean age of 21 years: the role of spinal deformity surgery. AB - BACKGROUND: Patients with neuromuscular disorders often have an increased risk of pneumonia and decreased lung function, which may further be compromised by scoliosis. Scoliosis surgery may improve pulmonary function in otherwise healthy patients, but no study has evaluated its effect on the risk of pneumonia in patients with neuromuscular scoliosis (NMS). METHODS: The patient charts of 42 patients (mean age 14.6 years) who had undergone surgery for severe NMS (mean scoliosis 86 degrees ) were retrospectively reviewed from birth to a mean of 6.1 years (range 2.8-9.5) after scoliosis surgery. The main outcome was radiographically confirmed pneumonia as a primary cause for hospitalization. We excluded postoperative (3 months) pneumonia from the analyses. RESULTS: The lifetime annual incidence of pneumonia was 8.0/100 before and 13.4/100 after scoliosis surgery (p > 0.10). The mean number of hospital days per year due to pneumonia were 0.59 (SD 2.3) before scoliosis surgery and 2.24 (SD 6.9) after surgery (p > 0.10). Multivariate analysis demonstrated that lifetime risk factors for pneumonia were epilepsy (RR 15.2, 95 % CI 1.3-176.8, p = 0.027), non-cerebral palsy (CP) etiology (RR = 10.2, 95 % CI 3.2-32.7, p < 0.001) and major scoliosis (main curve >70 degrees ; RR = 11.3, 95 % CI 1.8-70.7, p = 0.01). CONCLUSIONS: Epilepsy, non-CP etiology and major scoliosis are significant risk factors for pneumonia in patients with NMS. Scoliosis surgery does not decrease the incidence of pneumonia in patients with severe NMS. LEVEL OF EVIDENCE: Retrospective comparative study, Level III. PMID- 26350798 TI - Antimicrobial resistance and population structure of Staphylococcus aureus recovered from pigs farms. AB - Staphylococcus aureus is a burden in human and veterinary medicine. During the last decade, an increasing number of studies reported the presence of livestock associated methicillin-resistant S. aureus (LA-MRSA) clonal complex (CC) 398 in pigs. During 2013, a survey was performed in pig farms (n=328) randomly selected over Belgium, to monitor the current epidemiological situation of LA-MRSA among asymptomatic pigs and compare with former data to determine possible evolutions. Per farm, nose swabs were taken from 20 animals and pooled. MRSA was detected in 215 farms. Most isolates belonged to CC398 (n=211), and the remaining were ST9/t337 (n=1), ST80/t044 (n=2) and ST239/t4150 (n=1). A large diversity (n=19) of spa-types was found in the CC398 isolates. More than 90% of the isolates were non-wild type (NWT) to tetracycline and trimethoprim. NWT isolates were also found for ciprofloxacin (61.1%), clindamycin (64.4%), erythromycin (57.8%), kanamycin (43.1%) and gentamicin (45.5%). Microarray analysis showed that most CC398 isolates carried genes encoding resistance to tetracycline [tet(M)], macrolide-lincosamide-streptogramin group [erm(B), erm(C), lnu(A), vga(A)], aminoglycosides (aacA-aphD,aa dD, aphA3, sat) and/or phenicols (fexA). One CC398 isolate carried the multi-resistance gene cfr. The non-CC398 isolates carried virulence genes, as the egc-like cluster. The ST80 strain carried the Panton Valentine leukocidin gene and corresponded to the community-acquired (CA-)MRSA ST80-IV European clone. The MRSA prevalence among pigs in Belgium remains similar to previous studies but a larger diversity in spa-types has been detected in this study. The recovery of CA-MRSA from livestock indicates that one should remain vigilant to the evolution of LA-MRSA in pigs. PMID- 26350799 TI - Influence of gestational maternal feed restriction on growth performance and meat quality of rabbit offsprings. AB - The purpose of the present study was to evaluate the effect of feed restriction during pregnancy on reproductive performance of rabbit does and growth performance and meat quality of their offspring. A total of 26 primiparous non lactating does were equally divided into two treatment groups: the control group (C, n=13) that was fed ad libitum throughout gestation and the feed restricted group (R, n=13) that was fed to 75% of maintenance energy requirements from the 7(th) to the 26(th) day of gestation. Rabbit offsprings were weaned at 35 days of age and grown until the 72 days of age when they were slaughtered for meat quality assessment. Meat quality traits measured were pH(24), colour (L*, a*, b*), percentage of released water, cook loss, shear values and intramuscular fat. At kindling, R does produced smaller litter weights compared with those of does from group C, 447.8 and 591.4 g, respectively, and smaller individual kit birth weights, 56.2 and 71.5 g, respectively (P0.05). Performance and meat quality characteristics of fattening rabbits at 72 days of age were not influenced by gestational feed restriction of their mothers (P>0.05). Taking into consideration that, simultaneous gestation and lactation in rabbit does may be simulated by gestational feed restriction, results of the present study suggest that lactating does can support a simultaneous gestation without any adverse effect on the offsprings' quantitative and qualitative performance at the expense of increased mortality rates at parturition and until weaning. PMID- 26350800 TI - Facile fabrication of bactericidal and antifouling switchable chitosan wound dressing through a 'click'-type interfacial reaction. AB - A facile approach to functionalize chitosan (CS) non-woven surface with the bactericidal and antifouling switchable moieties is presented. Azlactone-cationic carboxybetaine ester copolymer was firstly prepared, then chemically attached onto CS non-woven surface through the fast and efficient 'click'-type interfacial reaction between CS primary amines and azlactone moieties. The CS non-woven surface functionalized with cationic carboxybetaine esters is able to kill bacteria effectively. Upon the hydrolysis of carboxybetaine esters into zwitterionic groups, the resulting zwitterionic surface can further prevent the attachment of proteins, platelets, erythrocytes and bacteria. This CS non-woven that switches from bactericidal performance during storage to antifouling property before its service has great potential in wound dressing applications. PMID- 26350801 TI - Bacillus amyloliquefaciens TSBSO 3.8, a biosurfactant-producing strain with biotechnological potential for microbial enhanced oil recovery. AB - A screening for biosurfactant-producing bacteria was conducted with 217 strains that were isolated from environmental samples contaminated with crude oil and/or petroleum derivatives. Although 19 promising biosurfactant producers were detected, strain TSBSO 3.8, which was identified by molecular methods as Bacillus amyloliquefaciens, drew attention for its production of a high-activity compound that presented an emulsification activity of 63% and considerably decreased surface (28.5 mN/m) and interfacial (11.4 mN/m) tensions in Trypticase Soy Broth culture medium. TSBSO 3.8 growth and biosurfactant production were tested under different physical and chemical conditions to evaluate its biotechnological potential. Biosurfactant production occurred between 0.5% and 7% NaCl, at pH values varying from 6 to 9 and temperatures ranging from 28 to 50 degrees C. Moreover, biosurfactant properties remained the same after autoclaving at 121 degrees C for 15 min. The biosurfactant was also successful in a test to simulate microbial enhanced oil recovery (MEOR). Mass spectrometry analysis showed that the surface active compound was a surfactin, known as a powerful biosurfactant that is commonly produced by Bacillus species. The production of a high efficiency biosurfactant, under some physical and chemical conditions that resemble those experienced in an oil production reservoir, such as high salinities and temperatures, makes TSBSO 3.8 an excellent candidate and creates good expectations for its application in MEOR. PMID- 26350802 TI - Characterization of the internal ion environment of biofilms based on charge density and shape of ion. AB - Biofilm polymers contain both electrically positively and negatively charged sites. These charged sites enable the biofilm to trap and retain ions leading to an important role of biofilm such as nutrient recycling and pollutant purification. Much work has focused on the ion-exchange capacity of biofilms, and they are known to adsorb ions through an exchange mechanism between the ions in solution and the ions adsorbed to the charged sites on the biofilm polymer. However, recent studies suggest that the adsorption/desorption behavior of ions in a biofilm cannot be explained solely by this ion exchange mechanism. To examine the possibility that a substantial amount of ions are held in the interstitial region of the biofilm polymer by an electrostatic interaction, intact biofilms formed in a natural environment were immersed in distilled water and ion desorption was investigated. All of the detected ion species were released from the biofilms over a short period of time, and very few ions were subsequently released over more time, indicating that the interstitial region of biofilm polymers is another ion reserve. The extent of ion retention in the interstitial region of biofilms for each ion can be determined largely by charge density, |Z|/r, where |Z| is the ion valence as absolute value and r is the ion radius. The higher |Z|/r value an ion has, the stronger it is retained in the interstitial region of biofilms. Ion shape is also a key determinant of ion retention. Spherical and non-spherical ions have different correlations between the condensation ratio and |Z|/r. The generality of these findings were assured by various biofilm samples. Thus, the internal regions of biofilms exchange ions dynamically with the outside environment. PMID- 26350803 TI - Amorphous calcium phosphate, hydroxyapatite and poly(d,l-lactic acid) composite nanofibers: Electrospinning preparation, mineralization and in vivo bone defect repair. AB - Due to the outstanding bioactivity and biocompatibility, calcium phosphate (CaP) based materials have been widely investigated for applications in the biomedical fields. In this study, amorphous calcium phosphate (ACP) nanospheres and hydroxyapatite (HA) nanorods have been prepared and hybridized with poly(d,l lactic acid) (PLA) to fabricate the composite nanofibers through electrospinning. The as-prepared ACP-PLA and HA-PLA composite nanofibers exhibit favorable mineralization behaviors in simulated body fluid (SBF). In the mineralization process, the ACP nanospheres and HA nanorods play an important role in the formation of HA nanosheets on the surface of composite nanofibers. The ACP-PLA and HA-PLA composite nanofibers show a high biocompatibility. The in vivo bone defect repair properties of the ACP-PLA and HA-PLA composite nanofibers are preliminarily investigated. The as-prepared ACP-PLA and HA-PLA composite nanofibers have promising applications in the biomedical fields. PMID- 26350804 TI - Vagus nerve stimulation during pregnancy: an instructive case. AB - BACKGROUND: Little is known about the safety of vagus nerve stimulation during pregnancy. CASE REPORT: Herein we report the case of a young woman affected by childhood-onset partial epilepsy, obesity, and depression in which a malfunctioning of VNS was detected during pregnancy. Although device functioning was not optimal during the critical period of organogenesis, no morphological abnormalities of the fetus were detected. CONCLUSION: A confirmation of VNS safety may increase its use during pregnancy, thus reducing possible systemic effects of antiepileptic drugs and antidepressants on the women and the baby. PMID- 26350805 TI - Lumbar ribs: a comprehensive review. AB - BACKGROUND: To date, no single comprehensive review has been published regarding lumbar ribs. Therefore, the present review was conducted to better elucidate these variant anatomical structures, which can be confused with transverse process fractures or result in miscounting of spine segments for surgical procedures. METHODS: Using standard search engines, a review of lumbar ribs was performed. CONCLUSIONS: Lumbar ribs are uncommon but can be misinterpreted on imaging or cause confusion during surgery. Mutations of the FGD1 or Hox10 gene may be involved in the development of lumbar ribs. Knowledge of these structures can decrease misdiagnosis when they are present. PMID- 26350806 TI - From the Editor: The physician as a personal teacher and guide. PMID- 26350807 TI - JCL Roundtable: Gender differences in reduction of CVD in response to lipid lowering drugs. AB - The Roundtable in this issue of the journal has to do with a very important topic that has generated much debate and confusion over the years. Do women and men need and receive the same type and intensity of drug therapy to appropriately reduce the incidence of major vascular events? Second, do women respond to lipid lowering medications with similar changes in lipoprotein levels and with equivalent reduction in major cardiovascular clinical events? I am very pleased to have 3 experts in different aspects of this issue. Dr Rachel Mackey is a cardiovascular epidemiologist in the University of Pittsburgh who is now actively involved in analyzing large data sets from community-based observational studies. Dr Thomas Pearson has many years of cardiovascular experience in clinical trials and observational studies that go to the issues faced by physicians in practice. He is the current Executive Vice President for Research and Education at the University of Florida Health Science Center. Dr Carl Orringer is a professor at the University of Miami School of Medicine who has years of experience in teaching preventive cardiology. PMID- 26350808 TI - Clinical lipidology: A subspecialty whose time has come. PMID- 26350809 TI - Validation of the Pooled Cohort equations in a long-term cohort study of Hong Kong Chinese. AB - BACKGROUND: The 2013 American College of Cardiology and the American Heart Association guidelines recommended the Pooled Cohort equations for evaluation of cardiovascular (CV) risk of individuals. OBJECTIVE: We investigated the usefulness of the Pooled Cohort equations in Chinese by validating this risk prediction model using the Hong Kong Cardiovascular Risk Factor Prevalence Study (CRISPS) cohort. METHODS: The Hong Kong CRISPS is a population-based prospective cohort study of CV risk factors among 2895 Chinese men and women (aged 25-74 years) initiated in 1995. CV events were ascertained until December 2012. The discrimination and calibration of the Pooled Cohort equations were evaluated and compared with the Framingham CV risk equation. A Hosmer-Lemeshow chi-square statistic (X(2)) of <20 indicated good calibration. RESULTS: The discrimination power of the 2 models in both men and women was moderate. The calibration score of both models were unacceptable in men (Pooled Cohort X(2), 24.1; Framingham X(2), 20.1), but was satisfactory in women (10.1 and 12.1, respectively). In men, with recalibration of the model using the CRISPS data, the accuracy of prediction improved. Recalibration, however, could not be applied to the Pooled Cohort model because the degree of miscalibration varied across the different risk categories. CONCLUSIONS: The Pooled Cohort equations provide poor calibration and moderate discrimination in Hong Kong Chinese, especially in men. In contrast, the Framingham CV risk equation can be applied to the Chinese population but requires recalibration in men. PMID- 26350810 TI - Apolipoprotein A-V concentration in preterm infants. AB - BACKGROUND: Fetal organs require much lipid for growth, but the cord blood had low TG concentrations, compared to adult serum. We investigated the association between the concentration of apolipoprotein A-V (apoA-V) and lipid profile in cord blood and neonatal serum. OBJECTIVE: ApoA-V was identified as an important determinant of plasma triglyceride concentrations. We sought to determine the association between serum apoA-V concentrations and lipoprotein profile in preterm infants and its early postnatal change. METHODS: Sixty-three neonates (35 males and 28 females; 15 term and 48 preterm) were included. Serum lipoprotein profile and apoA-V concentrations were determined at birth and 1 month. RESULTS: Cord blood apoA-V concentrations in appropriate-for-gestational age infants were extremely low (13.1 +/- 3.4 ng/mL in term infants, 4.4 +/- 0.9 ng/mL in preterm infants) compared with adult values, and those of small-for-gestational age infants were further low (6.4 +/- 4.2 ng/mL, 2.2 +/- 1.3 ng/mL, respectively). During the first month, serum apoA-V concentration markedly increased, and the concentration of preterm appropriate-for-gestational age infants caught up, whereas that of preterm small-for-gestational age infants did not. At birth, apoA V concentration positively correlated with gestational age (r = 0.354, P = .0069) but not with birth weight Z-score. ApoA-V concentration had a positive association with very low-density lipoprotein triglyceride concentrations (r = 0.646, P < .0001), and the relationships still remained at 1 month (r = 0.283, P = .0348). CONCLUSIONS: ApoA-V in neonates was unique in its serum concentration and in the association with lipoprotein profile. PMID- 26350811 TI - Varying relationship between 25-hydroxy-vitamin D, high density lipoprotein cholesterol, and serum 7-dehydrocholesterol reductase with sunlight exposure. AB - BACKGROUND: Cholesterol and cholecalciferol are synthesized from a common substrate 7-dehydrocholesterol. 7-dehydrocholesterol is converted to cholesterol by 7-dehydrocholesterol reductase enzyme (DHCR7) and to cholecalciferol by ultraviolet B radiation from sunlight. OBJECTIVE: To examine the effect of sunlight exposure and serum DHCR7 levels on cholecalciferol and cholesterol levels and studying any interrelationship. METHODS: In a cross-sectional observational study, 307 apparently healthy men (aged 40-60 years) were assessed for sunlight exposure, lipid levels, serum DHCR7, 25 hydroxyvitamin D (25(OH)D), body composition, and dietary milk calcium intake. RESULTS: Vitamin D deficiency (25(OH)D <20 ng/mL, 1 ng/mL = 2.496 nmols/L) was found in 56% of subjects. Serum 25(OH)D concentrations increased significantly with increasing duration of sunlight exposure (P < .05). At lower sunlight exposure (<1 h/d), serum 25(OH)D levels were positively associated with high-density lipoprotein cholesterol (HDL C) levels (P < .05) but at moderate sunlight exposure (1-2 h/d), there was no significant association. However, with higher sunlight exposure (>2 h/d), serum 25(OH)D concentrations were significantly negatively associated with HDL-C (P < .05). At moderate and higher sunlight exposure, an inverse significant relationship was observed between 25(OH)D and serum DHCR7 (P < .05); however, at lower sunlight exposure, no significant relationship was seen. CONCLUSIONS: 25(OH)D seems to show a varying relationship with HDL-C and serum DHCR7 at different durations of sunlight exposure. PMID- 26350812 TI - Salsalate-induced changes in lipid, lipoprotein, and apoprotein concentrations in overweight or obese, insulin-resistant, nondiabetic individuals. AB - BACKGROUND AND OBJECTIVE: Although salsalate administration consistently lowers plasma triglyceride concentrations in patients with type II diabetes, prediabetes, and/or insulin resistance, changes in low-density lipoprotein cholesterol (LDL-C) concentrations have been inconsistent; varying from no change to a significant increase. To evaluate the clinical relevance of this discordance in more detail, we directly measured LDL-C and obtained a comprehensive assessment of changes in lipid, lipoprotein, and apoprotein concentrations associated with salsalate use in insulin-resistant individuals, overweight or obese, but without diabetes, using vertical auto profile method. METHODS: A single-blind, randomized, placebo-controlled study was performed in volunteers who were overweight or obese, without diabetes, and insulin resistant on the basis of their steady-state plasma glucose concentration during an insulin suppression test. Participants were randomized 2:1 to receive salsalate 3.5 g/d (n = 27) or placebo (n = 14) for 4 weeks. Comprehensive lipid, lipoprotein, and apoprotein analysis by vertical auto profile was obtained after an overnight fast, before and after study intervention. RESULTS: There was no change in directly measured LDL-C concentration in salsalate-treated individuals. However, salsalate administration was associated with various changes considered to decrease atherogenicity; including decreases in triglyceride and total very low density lipoprotein cholesterol (VLDL-C) concentrations, a shift from small denser LDL lipoproteins toward larger, more buoyant LDL particles, decreases in VLDL(1+2)-C and LDL(4)-C, and nonsignificant decreases in non-high-density lipoprotein cholesterol and apolipoprotein B. No significant changes occurred in the placebo-treated group. CONCLUSIONS: Atherogenicity of the lipid, lipoprotein, and apoprotein profile of insulin-resistant individuals who were overweight or obese improved significantly in association with salsalate treatment. The clinical importance of this finding awaits further study. PMID- 26350813 TI - The apoB-to-PCSK9 ratio: A new index for metabolic risk in humans. AB - BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) shuttles low density lipoprotein (LDL) receptors for degradation, thus upregulates LDL plasma clearance. Although PCSK9 loss of function is cardioprotective, its role in metabolic risks remains unknown. Increased apoB-lipoproteins uptake into nonhepatic tissues such as white adipose tissue (WAT) induces their dysfunction, which may be favored by lower plasma PCSK9. We hypothesized that lower plasma PCSK9 relative to apoB, or higher apoB-to-PCSK9 ratio, is a better predictor of metabolic disturbances than PCSK9 alone in humans. METHODS: Thirty-three men and 48 postmenopausal women (>27 kg/m(2), aged 45-74 years, normoglycemic) underwent in-depth assessment of glucose and fat metabolism using high-fat meals, WAT biopsies, intravenous glucose-tolerance tests, and hyperinsulinemia clamps. RESULTS: Plasma apoB correlated positively with fasting and postprandial triglycerides and chylomicron clearance (R = 0.44-0.66) and glucose-stimulated insulin secretion (R = 0.24) and negatively with insulin sensitivity (R = -0.28) and gynoid WAT in situ lipoprotein lipase activity (ie, ex vivo WAT function, R(2) = 0.34). Neither PCSK9 nor LDL cholesterol associated with these risks. In regression analysis that adjusted for body mass index, lower plasma PCSK9 strengthened the association of apoB to WAT dysfunction and insulin resistance. Moreover, plasma apoB-to-PCSK9 ratio correlated positively with all these metabolic risks and further associated positively with android-to-gynoid fat ratio (R = 0.41) and negatively with gynoid fat mass (R = -0.23, all P <= .05). No significant sex differences existed in these associations. CONCLUSIONS: Lower plasma PCSK9 relative to apoB associates with metabolic risks and WAT dysfunction in normoglycemic obese subjects. We hypothesize that the plasma apoB-to-PCSK9 ratio provides a better clinical index than PCSK9 alone for monitoring early metabolic disturbances that may be promoted by reduction in plasma PCSK9. PMID- 26350814 TI - Screening and advanced lipid phenotyping in familial hypercholesterolemia: The Very Large Database of Lipids Study-17 (VLDL-17). AB - BACKGROUND: Familial hypercholesterolemia (FH) is an autosomal dominant dyslipidemia characterized by defective low-density lipoprotein (LDL) clearance. The aim of this study was to compare Friedewald-estimated LDL cholesterol (LDL-C) to biologic LDL-C in individuals screening positive for FH and then further characterize FH phenotypes. METHODS: We studied 1,320,581 individuals from the Very Large Database of Lipids, referred from 2009 to 2011 for Vertical Auto Profile ultracentrifugation testing. Friedewald LDL-C was defined as the cholesterol content of LDL-C, intermediate-density lipoprotein cholesterol, and lipoprotein(a) cholesterol (Lp(a)-C), with LDL-C representing biologic LDL-C. Using Friedewald LDL-C, we phenotypically categorized patients by the National Lipid Association guideline age-based screening thresholds for FH. In those meeting criteria, we categorized patients using population percentile-equivalent biologic LDL-C cutpoints and explored Lp(a)-C and remnant lipoprotein cholesterol (RLP-C) levels. RESULTS: Overall, 3829 patients met phenotypic criteria for FH by Friedewald LDL-C screening (FH+). Of those screening FH+, 78.8% were above and 21.2% were below the population percentile-equivalent biologic LDL-C. The mean difference in Friedewald biologic LDL-C percentiles was -0.01 (standard deviation, 0.17) for those above, and 1.92 (standard deviation, 9.16) for those below, respectively. Over 1 of 3 were found to have an elevated Lp(a)-C and over 50% had RLP-C greater than 95th percentile of the entire VLDL population. CONCLUSIONS: Of those who screened FH+, Friedewald and biologic LDL-C levels were closely correlated. Large proportions of the FH+ group had excess levels of Lp(a) C and RLP-C. Future studies are warranted to study these mixed phenotypic groups and determine the role for further risk stratification and treatment algorithms. PMID- 26350815 TI - Alcohol-independent beneficial cardiometabolic profile of individuals with hyper HDL cholesterolemia in Japanese men and women. AB - BACKGROUND: There is limited information on characterization of individuals with hyper-high-density lipoprotein (HDL) cholesterolemia. OBJECTIVES: The purpose of this study was to investigate the cardiometabolic profile of individuals with hyper-HDL cholesterolemia in comparison with the profile of individuals with normo-HDL cholesterolemia. METHODS: The subjects were Japanese men and women who had hyper-HDL cholesterolemia (>=100 mg/dL) and their control subjects who had normal HDL cholesterol levels (>=40 and <80 mg/dL) and were matched for age or age and alcohol consumption. The cardiometabolic profiles were compared between the hyper- and normo-HDL cholesterolemic groups. RESULTS: Both in men and women, body mass index, waist-to-height ratio, triglycerides, low-density lipoprotein cholesterol, and hemoglobin A1c were significantly lower in subjects with hyper HDL cholesterolemia than in subjects with normo-HDL cholesterolemia, whereas systolic and diastolic blood pressure levels were not significantly different between the 2 groups. In generalized estimating equation with adjustment for smoking and regular exercise, odds ratios of the hyper- vs normo-HDL cholesterolemic groups were significantly lower than the reference level of 1.00 for high body mass index, high waist-to-height ratio, hypertriglyceridemia, hyper low-density lipoprotein cholesterolemia, high lipid accumulation product, and metabolic syndrome. The previously mentioned results were obtained both in age matched analysis and in age- and alcohol intake-matched analysis, although the percentage of regular drinkers was significantly higher in the hyper-HDL cholesterolemic group than in the age-matched control group. CONCLUSIONS: Hyper HDL cholesterolemia was inversely associated with obesity, dyslipidemia, and metabolic syndrome in the analysis using alcohol intake-matched subject groups. Therefore, the association of hyper-HDL cholesterolemia with lower cardiometabolic risk is thought to be independent of habitual alcohol drinking. PMID- 26350816 TI - Efficacy and tolerability of coenzyme A vs pantethine for the treatment of patients with hyperlipidemia: A randomized, double-blind, multicenter study. AB - BACKGROUND: New, safer, and more effective agents to treat hyperlipidemia and thereby prevent cardiovascular events are under research. OBJECTIVE: To evaluate the lipid-lowering effects and safety of a natural hypolipidemic compound, coenzyme A (CoA) capsule, in Chinese patients with moderate dyslipidemia, compared with pantethine. METHODS: Overall, 216 subjects (124 males and 92 females; age, 18-75 years) with moderate dyslipidemia (triglyceride [TG], 2.3-6.5 mmol/L) were randomly divided into 2 groups administered CoA 400 U/d (n = 111) or pantethine 600 U/d (n = 105). Blood lipoproteins, liver and renal function, blood glucose, and complete blood count were measured at baseline and after 4- and 8 week treatment. RESULTS: TG reduction was 26.0% with CoA and 17.4% with pantethine after 4 weeks and 33.3% and 16.5% after 8 weeks; compared with baseline, the reduction was significant (P < .01) in both groups. The difference between the 2 groups was significant at both 4 weeks (P = .0413) and 8 weeks (P < .001). Compared with baseline, total cholesterol and non-high-density lipoprotein cholesterol (non-HDL-C) were reduced, whereas HDL-C was increased with CoA after 8 weeks (all P < .05). Compared with pantethine, total cholesterol (P = .026) and non-HDL-C (P = .005) were significantly reduced after 8 weeks of CoA treatment. There was no statistical difference in low-density lipoprotein cholesterol or HDL C between the 2 groups (P > .05) and no difference in blood glucose, hepatic or renal function, myopathy, or gastrointestinal tract symptoms. CONCLUSIONS: CoA can improve TG and other lipoprotein parameters to a greater extent than pantethine in moderate dyslipidemia, with no obvious adverse effects. PMID- 26350817 TI - Double filtration plasmapheresis in the treatment of pancreatitis due to severe hypertriglyceridemia. AB - BACKGROUND: Severe hypertriglyceridemia (HTG) leads to major complications such as acute pancreatitis. Lipoprotein apheresis has been proposed as a therapeutic tool for decreasing triglyceride levels, although experience is limited. OBJECTIVE: To describe our experience with double filtration plasmapheresis (DFPP) in patients with severe HTG and pancreatitis in the plasmapheresis unit of a tertiary hospital in Spain. METHODS: We recruited 4 patients with severe HTG (triglycerides [TGs] >1000 mg/dL) and acute pancreatitis. All the patients underwent DFPP as part of their treatment. Epidemiologic and laboratory data were collected before and after each plasmapheresis session. RESULTS: The average TG level before plasmapheresis was 3136 mg/dL (35.44 mmol/L; range, 1306-6693 mg/dL, 14.76-75.63 mmol/L), and the average Acute Physiology And Chronic Health Evaluation (APACHE) II level before the first session was 6 (range, 3-8). All patients made a full recovery, with a significant improvement in TG levels after plasmapheresis. The mean number of sessions was 2.1 (range, 1-3), and mean TG level after plasmapheresis was 428 mg/dL (4.84 mmol/L; range, 169-515 mg/dL; 1.91 5.82 mmol/L). After the first session, the mean decrease in TG levels was 69.16% (2169 mg/dL, range, 945-5925 mg/dL; 24.51 mmol/L, range, 10.78-66.95 mmol/L), and after the last session, TG levels fell by 89.09% (2794 mg/dL, range, 945-6198 mg/dL; 31.57 mmol/L, range, 10.68-70.04 mmol/L). None of the patients developed complications related to plasmapheresis. CONCLUSIONS: According to available evidence and our own experience, DFPP can be an effective and rapid treatment option in patients with severe HTG and complications. However, further research, including randomized controlled studies, is necessary. PMID- 26350818 TI - Frequency of familial hypercholesterolemia in patients with early-onset coronary artery disease admitted to a coronary care unit. AB - BACKGROUND: Familial hypercholesterolemia (FH) is the most common dominantly inherited cause of premature coronary artery disease (CAD). However, the diagnosis of FH in patients who have premature CAD in hospital settings is under recognized, this also represents a missed opportunity for screening their close family members and implementing primary prevention. OBJECTIVE: To investigate the point prevalence of FH in a coronary care unit (CCU) among patients with early onset CAD. METHODS: The prevalence of FH, based on modified phenotypic Dutch Lipid Clinic Network Criteria, and the spectrum of associated CAD risk factors, were investigated in a CCU setting. Data were collected on 175 coronary care patients with onset of CAD at age <60 years. RESULTS: The prevalence of probable/definite FH was 14.3% (95% confidence interval, 9.0%-19.5%); 46.3% of the patients gave a family history of premature CAD and 20.6% had an untreated low-density lipoprotein cholesterol >5.0 mmol/L. Diabetes, hypertension, obesity, and smoking were common and equally prevalent in patients with and without FH. CONCLUSIONS: FH is relatively frequent among patients with a history of early onset CAD in the CCU. Every effort should be made to detect FH in these patients and to initiate cascade testing of available family members to prevent the development of CAD in those who may be unaware that they also have the condition. PMID- 26350819 TI - Effects of change in high-density lipoprotein cholesterol by statin switching on glucose metabolism and renal function in hypercholesterolemia. AB - BACKGROUND: Recent reports have suggested that high-density lipoprotein (HDL) is metabolically related to glucose metabolism and renal function. Statin administration clinically increases HDL cholesterol (HDL-C). OBJECTIVE: To confirm that change in HDL-C by statin switching is associated with glucose metabolism and renal function in hypercholesterolemic patients. METHODS: In hypercholesterolemic outpatients (n = 129) who had taken either statin, as atorvastatin, pitavastatin, or rosuvastatin and switched to another statin, the relationship of change in HDL-C to glycated hemoglobin and estimated glomerular filtration rate (eGFR) was assessed. RESULTS: Change in HDL-C did not significantly correlate with change in HbA1c, eGFR calculated from creatinine (eGFRcre), and eGFR calculated from cystatin C (eGFRcys). The subjects were then divided into 2 groups by change in HDL-C: no change or decrease in HDL-C (HD group) and increase in HDL-C (HI group). In the HI group, apolipoprotein A-1 (Apo A-1) and eGFRs were significantly increased by statin switching. There were significant differences in changes in HDL-C, Apo A-1, lipoprotein lipase, glycated hemoglobin, and eGFR calculated from creatinine between the groups. In the patients with impaired glucose tolerance or diabetes, change in HbA1c was also significant between the groups. CONCLUSIONS: Our data suggest that an increase in HDL-C due to statin switching is associated with improvement in glucose metabolism and renal function. PMID- 26350820 TI - Identification and metabolic profiling of patients with lysosomal acid lipase deficiency. AB - BACKGROUND: Lysosomal acid lipase (LAL), encoded by the LIPA gene, catalyzes the intracellular hydrolysis of cholesteryl esters and triglycerides in hepatocytes and macrophages. LIPA defects cause accumulation of these lipids in lysosomes. LAL deficiency (LAL D) presents and progresses as a continuum with dyslipidemia, hepatomegaly, and liver fibrosis. OBJECTIVE: To improve the understanding of the genetic basis of LAL D, an underappreciated cause of dyslipidemia and cirrhosis, we studied DNA samples from patients with various phenotypes of dyslipidemia. METHODS: Participants (N = 1357) were identified by lipid profiles and screened for the common disease causing LIPA exon 8 skipping splice-site mutation (c.894G>A; p.Ser275_Gln298del; rs116928232). RESULTS: Six patients were heterozygous for this variant. Complete LIPA sequencing revealed a patient, subsequently confirmed to have LAL D, with a heterozygous frameshift mutation involving deletion of exon 4 (p.Gly77Valfs*17 c.230-106_c.428+541del). A family study revealed a sister with the same genotype and phenotype. Genetic, clinical, and lipoprotein profiles of these sisters plus 6 additional family members are reported. Profiles of 2 other LAL D patients monitored for 2 decades are presented. Cholesterol homeostasis was studied to investigate rates of cholesterol synthesis and absorption in 4 LAL D patients. High-density lipoprotein (HDL) subspecies were also analyzed. CONCLUSIONS: We used this LIPA sequencing strategy (detection of the relatively common exon 8 variant followed by complete gene sequencing to identify additional mutations) as a means to further elucidate the genetic basis of LAL D among individuals with a suggestive clinical phenotype. PMID- 26350821 TI - Minimally Invasive Versus Open Total Gastrectomy for Gastric Cancer: A Systematic Review and Meta-analysis of Short-Term Outcomes and Completeness of Resection : Surgical Techniques in Gastric Cancer. AB - Minimally invasive surgical techniques for gastric cancer are gaining more acceptance worldwide as an alternative to open resection. In order to assess the role of minimally invasive and open techniques in total gastrectomy for cancer, a systematic review and meta-analysis was performed. Articles comparing minimally invasive versus open total gastrectomy were reviewed, collected from the Medline, Embase, and Cochrane databases. Two different authors (JS and NW) independently selected and assessed the articles. Outcomes regarding operative results, postoperative recovery, morbidity, mortality, and oncological outcomes were analyzed. Statistical analysis portrayed the weighted mean difference (WMD) with a 95% confidence interval and odds ratio (OR). Out of 1242 papers, 12 studies were selected, including a total of 1360 patients, of which 592 underwent minimally invasive total gastrectomy (MITG). Compared to open total gastrectomy (OTG), MITG showed a longer operation time (WMD: 48.06 min, P < 0.00001), less operative blood loss (WMD: -160.70 mL, P < 0.00001), faster postoperative recovery, measured as shorter time to first flatus (WMD -1.05 days, P < 0.00001), shorter length of hospital stay (WMD: -2.43 days, P = 0.0002), less postoperative complications (OR 0.66, P = 0.02), similar mortality rates (OR 0.60, P = 0.52), and similar rates in lymph node yield (WMD -2.30, P = 0.06). Minimally invasive total gastrectomy showed faster postoperative recovery and less postoperative complications, whereas completeness of the resection was similar in both groups. Duration of surgery was longer in the minimally invasive group. Only comparative non-randomized studies were available, further emphasizing the need for a prospective randomized trial comparing MITG and OTG. PMID- 26350822 TI - Participation of PLA2 and PLC in DhL-induced activation of Rhinella arenarum oocytes. AB - Rhinella arenarum oocytes can be artificially activated, a process known as parthenogenesis, by a sesquiterpenic lactone of the guaianolide group, dehydroleucodine (DhL). Transient increases in the concentration of cytosolic Ca2+ are essential to trigger egg activation events. In this sense, the 1-4-5 inositol triphosphate receptors (IP3R) seem to be involved in the Ca2+ transient release induced by DhL in this species. We analyzed the involvement of phosphoinositide metabolism, especially the participation of phospholipase A2 (PLA2) and phospholipase C (PLC) in DhL-induced activation. Different doses of quinacrine, aristolochic acid (ATA) (PLA2 inhibitors) or neomycin, an antibiotic that binds to PIP2, thus preventing its hydrolysis, were used in mature Rhinella arenarum oocytes. In order to assay the participation of PI-PLC and PC- PLC we used U73122, a competitive inhibitor of PI-PLC dependent events and D609, an inhibitor of PC-PLC. We found that PLA2 inhibits quinacrine more effectively than ATA. This difference could be explained by the fact that quinacrine is not a specific inhibitor for PLA2 while ATA is specific for this enzyme. With respect to the participation of PLC, a higher decrease in oocyte activation was detected when cells were exposed to neomycin. Inhibition of PC-PLC with D609 and IP-PLC with U73122 indicated that the last PLC has a significant participation in the effect of DhL-induced activation. Results would indicate that DhL induces activation of in vitro matured oocytes of Rhinella arenarum by activation of IP PLC, which in turn may induce IP3 formation which produces Ca2+ release. PMID- 26350823 TI - A high performance triboelectric nanogenerator for self-powered non-volatile ferroelectric transistor memory. AB - We demonstrate an integrated module of self-powered ferroelectric transistor memory based on the combination of a ferroelectric FET and a triboelectric nanogenerator (TENG). The novel TENG was made of a self-assembled polystyrene nanosphere array and a poly(vinylidene fluoride) porous film. Owing to this unique structure, it exhibits an outstanding performance with an output voltage as high as 220 V per cycle. Meanwhile, the arch-shaped TENG is shown to be able to pole a bulk ferroelectric 0.65Pb(Mg1/3Nb2/3)O3-0.35PbTiO3 (PMN-PT) single crystal directly. Based on this effect, a bottom gate ferroelectric FET was fabricated using pentacene as the channel material and a PMN-PT single crystal as the gate insulator. Systematic tests illustrate that the ON/OFF current ratio of this transistor memory element is approximately 10(3). More importantly, we demonstrate the feasibility to switch the polarization state of this FET gate insulator, namely the stored information, by finger tapping the TENG with a designed circuit. These results may open up a novel application of TENGs in the field of self-powered memory systems. PMID- 26350824 TI - Development of a Website Providing Evidence-Based Information About Nutrition and Cancer: Fighting Fiction and Supporting Facts Online. AB - BACKGROUND: Although widely available, the general public, cancer patients, and cancer survivors have difficulties accessing evidence-based information on nutrition and cancer. It is challenging to distinguish myths from facts, and sometimes conflicting information can be found in different places. The public and patients would benefit from evidence-based, correct, and clear information from an easily recognizable source. OBJECTIVE: The aim of this project is to make scientific information available for the general public, cancer patients, and cancer survivors through a website. The aim of this paper is to describe and evaluate the development of the website as well as related statistics 1st year after its launch. METHODS: To develop the initial content for the website, the website was filled with answers to frequently asked questions provided by cancer organizations and the Dutch Dietetic Oncology Group, and by responding to various fiction and facts published in the media. The website was organized into 3 parts, namely, nutrition before (prevention), during, and after cancer therapy; an opportunity for visitors to submit specific questions regarding nutrition and cancer was included. The website was pretested by patients, health care professionals, and communication experts. After launching the website, visitors' questions were answered by nutritional scientists and dieticians with evidence- or eminence-based information on nutrition and cancer. Once the website was live, question categories and website statistics were recorded. RESULTS: Before launch, the key areas for improvement, such as navigation, categorization, and missing information, were identified and adjusted. In the 1st year after the launch, 90,111 individuals visited the website, and 404 questions were submitted on nutrition and cancer. Most of the questions were on cancer prevention and nutrition during the treatment of cancer. CONCLUSIONS: The website provides access to evidence- and eminence-based information on nutrition and cancer. As can be concluded from the number of visitors and the number of questions submitted to the website, the website fills a gap. PMID- 26350825 TI - Agency limits will only work if the cap fits. AB - Limits are to be imposed on the amount of money that many NHS organisations can spend on agency staff, it was announced last week. Every NHS trust that is yet to acquire foundation status - and those that have done so but since run into financial difficulty - will have to keep a tight lid on their spending on temporary nurses and other clinicians. PMID- 26350826 TI - Nurse attempts gruelling charity cycle ride. AB - A nurse who has previously cycled from Land's End to John O'Groats is preparing to take on what she believes will be an even tougher ride for charity. PMID- 26350827 TI - Trusts to cut back on agency costs as nursing staff spend gets capped. AB - The amount NHS trusts in England can spend on agency nurses will be capped under new rules announced by Monitor and the Trust Development Authority (TDA). PMID- 26350828 TI - Wanted: Your ideas for the next nursing strategy. AB - England's chief nurse Jane Cummings is urging nurses to tell her what the next nursing strategy should focus on. PMID- 26350829 TI - Call for personal health budgets 'culture change'. AB - Clinicians will need to rethink their approach to caring for patients using personal health budgets, the NHS England lead for personalisation and control policy said last week. PMID- 26350830 TI - A colourful approach to improving nutrition for people with dementia. AB - NHS wards are trialling the use of brightly coloured plates for people with dementia to investigate whether they are easier to see and use. PMID- 26350832 TI - Cummings' biggest challenge yet. AB - Transforming care for people with learning disabilities is challenging, England's chief nurse Jane Cummings said last week. PMID- 26350831 TI - Staffing issues must be addressed if health push is to succeed, says RCN. AB - A L5 million initiative to tackle the health of NHS workers will fail unless one of the biggest causes of stress - lack of staff - is addressed, the RCN has warned. PMID- 26350834 TI - RCN issues guidance on pain assessment and management. AB - Guidance detailing the competencies and skills that nurses and healthcare assistants need for assessing and managing pain have been published by the RCN. PMID- 26350835 TI - Adoption of EU-wide nursing strategy. AB - A Europe-wide strategy that sets out priorities for nursing and midwifery is due to be adopted this month. PMID- 26350836 TI - Students mark graduation day with lamp procession. AB - Nursing students from the University of Wolverhampton took part in a lamp procession at a local church last week to celebrate the completion of their degree programme. PMID- 26350837 TI - Academics draw up ten-point plan for pre-degree nursing scholarship. AB - A ten-point plan for a pre-degree 'scholarship' has been drawn up by academics in Scotland in a bid to give school pupils a chance to determine whether to pursue a nursing career. PMID- 26350838 TI - A testament to falling standards - or to greater transparency? AB - A staggering 205,289 written complaints were made to the NHS in England in 2014/15, equating to 562 per day. PMID- 26350844 TI - End of life care. AB - Essential facts According to the Office for National Statistics, 506,790 deaths were registered in England and Wales in 2013. In a report published earlier this year, the Parliamentary and Health Service Ombudsman said end of life care could be improved for up to 335,000 people every year in England. While an estimated three out of four deaths are expected, recognising when death is imminent can be challenging even for experienced palliative care clinicians, says the National Institute for Health and Care Excellence (NICE). PMID- 26350845 TI - When fear becomes the barrier to care. AB - A pilot clinic run by Barts Health NHS Trust in London offers cervical screening and psychological support to women who have experienced rape or sexual assault but are reluctant to go to a doctor. Its founder Pavan Amara, herself a rape survivor, is about to start nurse training this autumn. PMID- 26350846 TI - Feel-good factor of a healthy workforce. AB - New guidance from NICE recommends that employees' health and wellbeing should be a core priority for senior managers. Occupational health nurses on building sites and oil rigs are encouraging the mainly male staff to take up healthier diets and exercise and quit smoking. PMID- 26350859 TI - Talent spotting works for football, so why not the NHS? PMID- 26350860 TI - Disparity in student training leads to inconsistent skills. PMID- 26350861 TI - Nurses should address the need for extra eye-care support. PMID- 26350862 TI - We must take action against plans to 'modernise' pay and conditions. PMID- 26350863 TI - Be careful what you wish for from study into staff numbers. PMID- 26350864 TI - Ambulance services have come a long way, but targets haven't. PMID- 26350866 TI - What you're saying on our Facebook page.... on limiting the 1% rise to only some staff. PMID- 26350868 TI - How to perform a urinalysis. AB - RATIONALE AND KEY POINTS: This article aims to help nurses to undertake a urinalysis in a safe, timely, effective and patient-centred manner, ensuring privacy and dignity. Urinalysis is a common clinical procedure involving examination of urine to detect problems in the body. ? Urinalysis should be carried out by competent healthcare practitioners. ? Urinalysis is a simple, cost effective tool which can be performed for screening, diagnosis and management of conditions, because urine might undergo several changes as an individual becomes unwell. ? Urinalysis is an essential component of the holistic and symptomatic assessment of any individual in poor health. ? The healthcare practitioner should explain the procedure to patients. ? The healthcare practitioner should document relevant findings. REFLECTIVE ACTIVITY: Clinical skills articles can help update your practice and ensure it remains evidence based. Apply this article to your practice. Reflect on and write a short account of: 1. How reading this article will change your practice. 2. The learning points you have identified, and how you can dissesminate these points to your colleagues. 3. Any further learning needs you have identified. Subscribers can upload their reflective accounts at: rcni.com/portfolio. PMID- 26350869 TI - Measuring patient dependency in the emergency department. AB - The Jones Dependency Tool can be used in emergency departments to improve patient care and identify the required staffing and skill mix. Using the tool, the nurse can accurately identify a patient's specific nursing needs. The dependency tool is used to evaluate patients' needs in six areas: communication; airway, breathing and circulation; mobility; eating, drinking, elimination and personal care; environmental safety, health and social needs; and triage. Appropriate nursing care can be tailored to the dependency level, depending on whether the dependency level is low, moderate, high or total dependency. PMID- 26350870 TI - Evaluating the VERA framework for communication. AB - This article describes an evaluation of the use of the VERA (validation, emotion, reassurance, activity) framework for communication in a practice development unit at North Essex Partnership University NHS Foundation Trust. Staff of two older adult inpatient wards in the Crystal Centre received training on the VERA framework and applied it to their practice. They found the VERA framework to be practical and user friendly, and to result in compassionate communication. Staff found that focusing on meaningful, creative interactions with service users and making a connection with these individuals is important. PMID- 26350871 TI - Helping patients to learn about self-management. AB - Nurses are often urged to help patients learn about their illness and the self management measures that may enable them to achieve a degree of independence after they have left hospital. However, little has been written about the practical process of facilitating patient learning while the patient makes sense of their circumstances and considers what they can do to manage any necessary lifestyle changes. Educational articles tend to focus on programmed learning, such as educational courses delivered to groups of patients with similar conditions. This article assists the nurse in reviewing what learning might entail for a patient and to explore why this type of learning is different to learning in other circumstances. PMID- 26350872 TI - Stigmatised patients. AB - Individuals at increased risk of stigmatisation include those with particular physical traits or perceived character 'blemishes'. PMID- 26350873 TI - A specialty in crisis. AB - Around half of diabetes specialist nurses are expected to retire in the next decade, and one third of hospitals now have no specific diabetes inpatient specialist nurses. Yet the NHS is not recruiting enough of these clinicians to keep pace with the growing numbers diagnosed with diabetes - now increasing by more than 100,000 annually. PMID- 26350875 TI - Feeling the pressure at work. AB - Nursing can be a particularly stressful profession. It is not just physically demanding, but mentally and emotionally draining too. PMID- 26350876 TI - My work is unique. AB - I am clinical nurse lead for Local Care Force, an agency that provides nurses to care homes, intermediate care units and private hospitals in Yorkshire. PMID- 26350877 TI - Student life - Open for discussion. AB - The Freedom to Speak Up review has exposed a culture of intimidation and bullying in many parts of the NHS. PMID- 26350878 TI - Genome-wide association study for rotator cuff tears identifies two significant single-nucleotide polymorphisms. AB - BACKGROUND: The precise etiology of rotator cuff disease is unknown, but prior evidence suggests a role for genetic factors. Limited data exist identifying specific genes associated with rotator cuff tearing. The purpose of this study was to identify specific genes or genetic variants associated with rotator cuff tearing by a genome-wide association study with an independent set of rotator cuff tear cases. MATERIALS AND METHODS: A set of 311 full-thickness rotator cuff tear cases genotyped on the Illumina 5M single-nucleotide polymorphism (SNP) platform were used in a genome-wide association study with 2641 genetically matched white population controls available from the Illumina iControls database. Tests of association were performed with GEMMA software at 257,558 SNPs that compose the intersection of Illumina SNP platforms and that passed general quality control metrics. SNPs were considered significant if P < 1.94 * 10(-7) (Bonferroni correction: 0.05/257,558). RESULTS: Tests of association revealed 2 significantly associated SNPs, one occurring in SAP30BP (rs820218; P = 3.8E-9) on chromosome 17q25 and another occurring in SASH1 (rs12527089; P = 1.9E-7) on chromosome 6q24. CONCLUSIONS: This study represents the first attempt to identify genetic factors influencing rotator cuff tearing by a genome-wide association study using a dense/complete set of SNPs. Two SNPs were significantly associated with rotator cuff tearing, residing in SAP30BP on chromosome 17 and SASH1 on chromosome 6. Both genes are associated with the cellular process of apoptosis. Identification of potential genes or genetic variants associated with rotator cuff tearing may help in identifying individuals at risk for the development of rotator cuff tearing. PMID- 26350879 TI - Shoulder arthroplasty for atraumatic osteonecrosis of the humeral head. AB - BACKGROUND: Osteonecrosis (ON) of the humeral head represents <5% of the shoulder arthroplasty population. Depending on the stage of disease, surgeons must decide between hemiarthroplasty (HA) and total shoulder arthroplasty (TSA). To date, the peer-reviewed literature offers minimal insight into the best form of treatment of this population of patients. METHODS: Between August 1973 and November 2010, 141 shoulder arthroplasties were performed for operatively confirmed ON of the humeral head; 67 HAs and 71 TSAs were observed for at least 2 years (mean, 9.3 years) or until reoperation. Indications for surgery included imaging-confirmed ON in a patient who had failed to respond to conservative treatment modalities. RESULTS: Shoulder arthroplasty provided significant improvements in pain scores (P < .001), elevation (P < .01), and external rotation (P < .01) for both the HA and TSA populations. Both groups showed similar patient-reported satisfaction (>75%) and excellent/satisfactory Neer ratings (>65%). Eleven percent of HAs had moderate to severe glenoid erosion at follow-up, and 25% of glenoid components were radiographically at risk. Eight HAs and 11 TSAs underwent reoperation. The most common cause for reoperation was painful glenoid arthrosis in the HA group (7) and aseptic loosening (4) in the TSA group. The estimated 20-year survivorship of HA and TSA was 87% and 79%, respectively. CONCLUSIONS: In patients with atraumatic ON of the humeral head, both HA and TSA can be expected to provide lasting pain relief and improved range of motion, with HA having longer follow-up. HA should be strongly considered in patients with atraumatic ON of the humeral head and preserved glenoid cartilage. PMID- 26350880 TI - Correlation between glenoid inclination and critical shoulder angle: a radiographic and computed tomography study. AB - BACKGROUND: Increased critical shoulder angles consist of both the acromial cover and glenoid inclination and have been found in patients with rotator cuff pathology. The purpose of this study was to determine the correlation of the critical shoulder angle and glenoid inclination and to determine the difference in glenoid inclination between patients with osteoarthritis and massive rotator cuff tears. METHODS: The critical shoulder angle and glenoid inclination were measured on anteroposterior radiographs, and glenoid inclination was also measured on a validated 3-dimensional computer software program of 50 shoulders undergoing primary total shoulder arthroplasty. Twenty-five shoulders had osteoarthritis and A1 glenoids, as defined by the Walch classification, and were undergoing anatomic shoulder arthroplasty. The other 25 shoulders had massive rotator cuff tears and E0 glenoids, as defined by the Favard classification. The 2 groups were compared. RESULTS: Critical shoulder angle and glenoid inclination were significantly correlated (R(2) = 0.7426, P < .001). Shoulders with massive rotator cuff tears (E0) demonstrated increased glenoid inclination measurements than shoulders with osteoarthritis (A1). As measured by the 3-dimensional software, the massive rotator cuff group had a glenoid inclination of 13.6 degrees +/- 4.3 degrees and the osteoarthritis group had a glenoid inclination of 4.7 degrees +/- 5.6 degrees . When measured by anteroposterior radiographs, the average glenoid inclination was 13.6 degrees +/- 4.6 degrees in the massive rotator cuff group and was 7.6 degrees +/- 5.01 degrees in the osteoarthritic group . CONCLUSION: Glenoid inclination is linearly correlated with the critical shoulder angle and is significantly increased in patients with massive rotator cuff tears. PMID- 26350881 TI - An update on liver transplantation: A critical review. AB - Liver transplantation, although now a routine procedure, with defined indications and usually excellent outcomes, still has challenges. Donor shortage remains a key issue. Transplanted organs are not free of risk and may transmit cancer, infection, metabolic or autoimmune disease. Approaches to the donor shortage include use of organs from donors after circulatory death, from living donors and from those previously infected with Hepatitis B and C and even HIV for selected recipients. Normothermic regional and/or machine perfusion, whether static or pulsatile, normo- or hypothermic, are being explored and will be likely to have a major place in improving donation rates and outcomes. The main indications for liver replacement are alcoholic liver disease, HCV, non-alcoholic liver disease and liver cancer. Recent studies have shown that selected patients with severe alcoholic hepatitis may also benefit from liver transplant. The advent of new and highly effective treatments for HCV, whether given before or after transplant will have a major impact on outcomes. The role of transplantation for those with liver cell cancer continues to evolve as other interventions become more effective. Immunosuppression is usually required life-long and adherence remains a challenge, especially in adolescents. Immunosuppression with calcineurin inhibitors (primarily tacrolimus), antimetabolites (azathioprine or mycophenolate) and corticosteroids remains standard. Outcomes after transplantation are good but not normal in quality or quantity. Premature death may be due to increased risk of cardiovascular disease, de novo cancer, recurrent disease or late technical problems. PMID- 26350882 TI - Screening for distant metastases in head and neck cancer patients using FDG-PET and chest CT: validation of an algorithm. AB - In patients with head and neck squamous cell carcinoma and high-risk factors, the combination of whole body FDG-PET and contrast-enhanced chest CT has the highest sensitivity and accuracy when screening for distant metastases. The aim of the present study was to retrospectively validate an earlier developed algorithm for interpreting the combination of screening PET and CT. The test cohort consisted of 47 consecutive HNSCC patients with high-risk factors for distant metastases, who had previously undergone FDG-PET and CT and had a minimum 12 months of follow up. In 12 (26 %) patients, distant metastases were detected during screening or within 12-month follow-up. In patients with locoregional control during follow up, the sensitivity and specificity were 55 % (95 % CI 23-83 %) and 97 % (95 % CI 82-99 %), respectively, for chest CT, 55 % (95 % CI 23-83 %) and 100 % (95 % CI 88-100 %), respectively, for PET and 73 % (95 % CI 39-94 %) and 100 % (95 % CI 88 100 %), respectively, for the combination of PET and CT. The proposed algorithm was considered to have been validated. In this algorithm, all FDG-PET positive scans for distant metastases (regardless of interpretation of a solid lung lesion on CT) and CT scans with suspicious pulmonary lesions of less than 5-mm diameter (regardless of FDG-PET findings) are considered positive for distant metastases. PMID- 26350883 TI - Opportunities for utilization of non-conventional energy sources for biomass pretreatment. AB - The increasing concerns over the depletion of fossil resources and its associated geo-political issues have driven the entire world to move toward sustainable forms of energy. Pretreatment is the first step in any biochemical conversion process for the production of valuable fuels/chemicals from lignocellulosic biomass to eliminate the lignin and produce fermentable sugars by hydrolysis. Conventional techniques have several limitations which can be addressed by using them in tandem with non-conventional methods for biomass pretreatment. Electron beam and gamma (gamma)-irradiation, microwave and ultrasound energies have certain advantages over conventional source of energy and there is an opportunity that these energies can be exploited for biomass pretreatment. PMID- 26350884 TI - Antibodies against carbamylated proteins are present in primary Sjogren's syndrome and are associated with disease severity. AB - OBJECTIVES: Herein, we investigate the presence and prognostic value of autoantibodies against carbamylated proteins (anti-CarP) in the serum of patients with primary Sjogren's syndrome (pSS). PATIENTS AND METHODS: Serum levels of anti CarP antibodies were measured in Norwegian patients with pSS (n=78) and corresponding controls (n=74) using ELISA and analysed in relation with exocrine gland function, degree of salivary gland inflammation, signs of ectopic germinal centre (GC) formation and immunological markers. For univariate comparisons, the Mann-Whitney U test and chi(2) or Fisher's exact tests were used. Correlations were assessed with Spearman's rank testing. Multivariate regression analyses were used to assess the effect of anti-CarP positivity on clinical manifestations. RESULTS: Of the patients with pSS, 27% were positive for anti-CarP IgG antibodies. Levels of anti-CarP correlated positively with total IgG, IgM, rheumatoid factor and beta2-microglobulin. Importantly, after adjusting for confounding factors, patients positive for anti-CarP had significantly higher focus score. Furthermore, positive anti-CarP status coincided with 9.2-fold higher odds of having developed GC-like structures in the minor salivary glands. As a patient group considered having worse disease outcome, individuals with ectopic GC-like structures also presented with significantly higher levels of anti-CarP antibodies. CONCLUSIONS: Presence of anti-CarP in patients with pSS is strongly associated with increased focal lymphocytic infiltration, formation of ectopic GC-like structures in minor salivary glands, and diminished salivary gland function. Even taking into consideration our relatively small cohort we believe that anti-CarP antibodies offer new possibilities for identifying patients with more active disease and at risk of developing additional comorbidity. PMID- 26350885 TI - Methods and Results Report - Evidence and consensus-based (S3) Guidelines for the Treatment of Actinic Keratosis -International League of Dermatological Societies in cooperation with the European Dermatology Forum. PMID- 26350886 TI - EPLIN: a fundamental actin regulator in cancer metastasis? AB - Treatment of malignant disease is of paramount importance in modern medicine. In 2012, it was estimated that 162,000 people died from cancer in the UK which illustrates a fundamental problem. Traditional treatments for cancer have various drawbacks, and this creates a considerable need for specific, molecular targets to overcome cancer spread. Epithelial protein lost in neoplasm (EPLIN) is an actin-associated molecule which has been implicated in the development and progression of various cancers including breast, prostate, oesophageal and lung where EPLIN expression is frequently lost as the cancer progresses. EPLIN is important in the regulation of actin dynamics and has multiple associations at epithelial cells junctions. Thus, EPLIN loss in cancer may have significant effects on cancer cell migration and invasion, increasing metastatic potential. Overexpression of EPLIN has proved to be an effective tool for manipulating cancerous traits such as reducing cell growth and cell motility and rendering cells less invasive illustrating the therapeutic potential of EPLIN. Here, we review the current state of knowledge of EPLIN, highlighting EPLIN involvement in regulating cytoskeletal dynamics, signalling pathways and implications in cancer and metastasis. PMID- 26350888 TI - Genetic characterization of natural reassortant H4 subtype avian influenza viruses isolated from domestic ducks in Zhejiang province in China from 2013 to 2014. AB - The H4 subtype of the influenza virus was first isolated in 1999 from pigs with pneumonia in Canada. H4 avian influenza viruses (AIVs) are able to cross the species barrier to infect humans. In order to better understand the genetic relationships between H4 AIV strains circulating in Eastern China and other AIV strains from Asia, a survey of domestic ducks in live poultry markets was undertaken in Zhejiang province from 2013 to 2014. In this study, 23 H4N2 (n = 14) and H4N6 (n = 9) strains were isolated from domestic ducks, and all eight gene segments of these strains were sequenced and compared to reference AIV strains available in GenBank. The isolated strains clustered primarily within the Eurasian lineage. No mutations associated with adaption to mammalian hosts or drug resistance was observed. The H4 reassortant strains were found to be of low pathogenicity in mice and able to replicate in the lung of the mice without prior adaptation. Continued surveillance is required, given the important role of domestic ducks in reassortment events leading to new AIVs. PMID- 26350889 TI - It's About Time. PMID- 26350890 TI - How to Hit a Home Run with Bundled Payments. AB - As health care payment reform continues to evolve, reimbursement increasingly is being linked to outcomes as well as to expenditures. Toward this end, the Centers for Medicare & Medicaid Services has established models for "bundled" payments to long-term care providers, using predetermined payments based on historical spending rates, in a new pay-for-performance landscape. The goal is to reward providers for quality and cost-effective care as well as penalize them for adverse patient outcomes and hospital readmissions based on the target spending rates. Pharmacists have a role in these new models of care, but need to broaden their partnerships and relationships with providers and be prepared to prove they are contributing both to quality care and to reducing costs. PMID- 26350891 TI - Antimicrobial Therapy in Long-Term Care: Controversy, Colonization, and Criteria. AB - OBJECTIVE: To empower pharmacists to improve the outcomes of residents in long term care facilities with urinary tract (UTIs) and skin and soft-tissue infections (SSTIs). DATA SOURCES: Relevant articles published since 1990 to date were found via PubMed regarding: long-term care, urinary tract infection, skin and soft-tissue infection, antimicrobials, multi-drug-resistant organisms, antimicrobial resistance, and dementia. Two additional Web sites were included for pharmacists' resources. A total of 28 sources were used (studies, Web sites, and review articles). STUDY SELECTION: Sixteen studies were included regarding treatment of suspected infections, antimicrobial resistance of organisms present in long-term care facilities, and interventions previously attempted toward antimicrobial stewardship. DATA EXTRACTION: The types of infection seen in long term care facilities were narrowed to UTIs and SSTIs. Data were extracted regarding the type/resistance of bacteria and treatment outcomes. DATA ANALYSIS: The review demonstrates growing antimicrobial resistance in long-term care for pathogens causing UTIs and SSTIs. The review outlines guidelines for the treatment of such infections, and the incidence of asymptomatic bacteriuria, and subsequent overtreatment. Also included is a discussion of antimicrobial usage in dementia and resources for antimicrobial stewardship. CONCLUSION: Pharmacists can aid with antimicrobial stewardship in long-term care by educating providers on the need for changes in prescribing habits and the criteria for treating UTIs and SSTIs. PMID- 26350892 TI - Topical Metronidazole for Odor Control in Pressure Ulcers. AB - There are many remedies that have been recommended for the treatment of foul odor associated with pressure ulcers. This article seeks to review the literature surrounding the use of metronidazole as a safe and effective solution to an oftentimes stubborn and frustrating problem. Other tools used to control odor include bleach-based solutions and charcoal dressings. Metronidazole, with its antianaerobic properties, appears to have a useful role in therapy when applied topically to a pressure ulcer. Commercially available products include 0.75% and 1% creams, gels, lotions, and intravenous solutions. Of the 59 cases viewed throughout several publications, 56 reported nearly complete odor resolution in two to seven days when metronidazole was applied to the wound two or three times daily. Virtually no systemic adverse events have been reported in the literature, despite the risk for systemic absorption. A need remains to monitor for toxicities such as nausea, gastrointestinal distress, and neural toxicities from long-term use. PMID- 26350893 TI - Polypharmacy, the Elderly, and Deprescribing. AB - The risks of polypharmacy are heightened in the elderly because of a number of factors including age-related physiologic changes and the presence of comorbid conditions. Polypharmacy is a strong predictor of potentially inappropriate medication (PIM) use in the elderly in which harm may outweigh potential benefits. Despite available lists and criteria of PIMs from expert panels regarding inappropriate use of medications for older adults, prescribing of PIMs continues to be reported. Empowering clinicians with evidence-based guidance to safely and effectively discontinue PIMs by "deprescribing" is the subject of current research. Pharmacists can play an important role as part of the circle of care for the elderly. The acronym "MINDFUL" serves as a reminder of steps commonly used by pharmacists to assess appropriateness of medications and optimize health outcomes for their senior patients. PMID- 26350894 TI - Clinical Burden and Nonpharmacologic Management of Nursing Facility Residents with Overactive Bladder and/or Urinary Incontinence. AB - OBJECTIVE: To identify clinical characteristics of residents with a diagnosis of overactive bladder (OAB) and/or urinary incontinence (UI) to determine the prevalence of comorbidities, severe mobility impairment (SMI), moderate-to-severe cognitive impairment (MSCI), and a toileting program and the response to that program. DESIGN: Cross-sectional retrospective analysis. SETTING: Skilled nursing facilities. PATIENTS, PARTICIPANTS: Residents with a diagnosis of OAB and/or UI and an age range, and gender frequency-matched 1:1 control cohort without OAB and/or UI. INTERVENTIONS: None. MAIN OUTCOME MEASURE(S): De-identified Minimum Data Set data 3.0 records (October 1, 2010, to September 30, 2012). RESULTS: Of the 175,632 residents, 65% had a diagnosis of UI and 1% had a diagnosis of OAB. Those with UI and/or OAB were more likely to have MSCI (mean Brief Inventory of Mental Status score 10.2 +/- 4.5 vs. 12.5 +/- 3.6; P = 0.001) and SMI (49.4% vs. 26.4%; P < 0.001), multiple comorbid conditions, falls and falls with injury, hip fractures (5.5% vs. 4.9%; P < 0.001), urinary tract infections (21.4% vs. 16.5%; P = 0.001), and moisture-associated skin damage (5.2% vs. 2.6%; P = 0.001) than the control cohort. Toileting programs were attempted more often (17.0% vs. 5.1%; P < 0.001) in those with UI and/or OAB but were only minimally successful, with 4.2% having decreased wetness and 0.9% being completely dry. CONCLUSION: Residents with UI and/or OAB exhibit a higher burden of MSCI, SMI, and comorbidities than do residents without these diagnoses. Nonpharmacologic therapies such as toileting programs should be a primary focus in the nursing facility. PMID- 26350895 TI - Sweeping CMS Proposal Would Acknowledge Role of Pharmacists. PMID- 26350896 TI - T1rho MRI of healthy and fibrotic human livers at 1.5 T. AB - BACKGROUND: Liver fibrosis is a public health problem worldwide. There is a need of noninvasive imaging based methods for better diagnosis of this disease. In the current study, we aim to evaluate the potential of T1rho MRI technique in detecting and characterizing different grades of liver fibrosis in vivo in humans. METHODS: Healthy subjects and patients with liver fibrosis were prospectively recruited for T1rho MRI of liver on a 1.5 T MR scanner. Single slice T1rho weighted images were acquired at different spin lock duration (0, 10, 20 and 30 ms) with spin lock amplitude of 500 Hz in a single breath-hold. Additionally, liver's T1rho images were acquired from five healthy subjects on the same day (n = 2) and different day (n = 2) sessions for test-retest study. Liver biopsy samples from patients were obtained and used to calculate the METAVIR score to define the stage of fibrosis and inflammation grade. T1rho maps were generated followed by computation of mean and standard deviation (SD) values. Coefficient of variation (COV) of T1rho values between two MRI scans was computed to determine reproducibility in liver. T test was used to compare T1rho values between healthy and fibrotic liver. Pearson correlation was performed between stages of liver fibrosis and T1rho values. RESULTS: The mean (SD) T1rho value among subject with healthy liver was 51.04 (3.06) ms. The COV of T1rho values between two repetitions in the same day session was 0.83 +/- 0.8% and in different day session was 5.4 +/- 2.7%. T1rho values in fibrotic liver were significantly higher compared to those of healthy liver (p < 0.05). A statically significant correlation between stages of fibrosis and T1rho values was observed (r = 0.99, p < 0.05). Inflammation score for one patient was 2 and for remaining patients it was 1. CONCLUSIONS: Proposed T1rho pulse sequence design and protocol enabled acquisition of a single slice T1rho weighted images in a single breath hold and hence mitigated breathing motion related artifacts. Preliminary results have shown the sensitivity of T1rho values to changes induced by liver fibrosis, and may potentially be used as a clinical biomarker to delineate the stages of liver fibrosis. Further, studies on a large number of subjects are required to validate the observations of the current study. Nevertheless, T1rho imaging can be easily setup on a clinical scanner to monitor the progression of liver fibrosis and to the evaluate efficacy of anti-fibrotic drugs. PMID- 26350897 TI - Influence of oxic/anoxic condition on sorption behavior of PFOS in sediment. AB - Sediment components and redox properties change with oxic/anoxic condition, which affect the environmental transport of perfluorooctane sulfonate (PFOS). Herein, the influence of oxic/anoxic condition on the variation of redox and residual components of sediments, where organic matter, iron and manganese oxides are separated from the original sediment collected from Lake Taihu, China, are investigated. Meanwhile, the distinguishing sorption behaviors of PFOS on various residual sediments under oxic and anoxic condition are studied. Sediment after extracting iron and manganese (S-FeMn), which possessed the highest organic carbon (0.99%), had the highest affinity for PFOS under oxic condition. However, anoxic environment resulted in an increase of the pH, dissolving of organic carbon and de-protonation of S-FeMn, which caused the lower sorption capacity of PFOS on S-FeMn. Sediment after extracting manganese (S-Mn) had the higher sorption ability in anoxic environment because the Fe(2+) from S-Mn provided more effective electrostatic sites for anionic PFOS. When the environment changed to oxic condition, the iron existed as trivalent form in S-Mn, which resulted in a block of effective sorption site and reduced the sorption amounts of PFOS. The higher percentage of manganese oxides restrained the sorption of PFOS. Hence, whether or not oxic/anoxic condition promoted the PFOS sorption depended on both the percentage and form of various components in the sediment. The study generated further insight into the environmental transport of PFOS in the sediments with different properties and the wetland system, where oxic/anoxic subsurface flow was constructed. PMID- 26350898 TI - Acute Toxicity Assessment of Reactive Red 120 to Certain Aquatic Organisms. AB - Laboratory experiments were conducted to evaluate the acute toxicity of a widely used textile dye namely Reactive Red 120 (RR 120) on certain aquatic species such as Pseudokirchneriella subcapitata (green alga), Lemna gibba (duck weed), Daphnia magna (water flea) and Oncorhynchus mykiss (Rainbow trout). All experiments were performed as per the OECD Guidelines for Testing of Chemicals. The toxicity end points of EC50, LC50, NOEC and LOEC for RR 120 were determined with 95% confidence limits using TOX STAT version 3.5. The EC50 of RR 120 for green alga, duck weed and water flea are >100.00, 64.34, 10.40 mg L(-1), respectively and LC50 for Rainbow trout is 78.84 mg L(-1). Based on the results, the test item RR 120 could be classified as non-toxic to green alga, harmful to duck weed and Rainbow trout, toxic to water flea. PMID- 26350899 TI - Investigating Role of Abiotic Factors on Spinosad Dissipation. AB - The effect of abiotic factors on dissipation of spinosad (soil moisture regimes, pH, and light) was studied. Spinosad residues were estimated using high performance liquid chromatography fitted with a UV detector. Under laboratory conditions, half-lives of spinosad were 9.0 and 7.7 days for air dried and field capacity soils, respectively. Percent dissipation of spinosad after 30 days was 47.02, 22.35, 62.5, 68.23 and 76.47 in solution with an aqueous pH of 10.85, 9.15, 6.97, 3.90 and 2.04, respectively. The half-life of spinosad in UV and sunlight was only 1.6 and 5.2 h, respectively. Light, especially the UV component, is an important factor for degradation of spinosad compared to other abiotic conditions. PMID- 26350900 TI - The E3 ligase RNF43 inhibits Wnt signaling downstream of mutated beta-catenin by sequestering TCF4 to the nuclear membrane. AB - Given its fundamental role in development and cancer, the Wnt-beta-catenin signaling pathway is tightly controlled at multiple levels. RING finger protein 43 (RNF43) is an E3 ubiquitin ligase originally found in stem cells and proposed to inhibit Wnt signaling by interacting with the Wnt receptors of the Frizzled family. We detected endogenous RNF43 in the nucleus of human intestinal crypt and colon cancer cells. We found that RNF43 physically interacted with T cell factor 4 (TCF4) in cells and tethered TCF4 to the nuclear membrane, thus silencing TCF4 transcriptional activity even in the presence of constitutively active mutants of beta-catenin. This inhibitory mechanism was disrupted by the expression of RNF43 bearing mutations found in human gastrointestinal tumors, and transactivation of the Wnt pathway was observed in various cells and in Xenopus embryos when the RING domain of RNF43 was mutated. Our findings indicate that RNF43 inhibits the Wnt pathway downstream of oncogenic mutations that activate the pathway. Mimicking or enhancing this inhibitory activity of RNF43 may be useful to treat cancers arising from aberrant activation of the Wnt pathway. PMID- 26350901 TI - Oxidized LDL-bound CD36 recruits an Na+/K+-ATPase-Lyn complex in macrophages that promotes atherosclerosis. AB - One characteristic of atherosclerosis is the accumulation of lipid-laden macrophage foam cells in the arterial wall. We have previously shown that the binding of oxidized low-density lipoprotein (oxLDL) to the scavenger receptor CD36 activates the kinase Lyn, initiating a cascade that inhibits macrophage migration and is necessary for foam cell generation. We identified the plasma membrane ion transporter Na(+)/K(+)-ATPase as a key component in the macrophage oxLDL-CD36 signaling axis. Using peritoneal macrophages isolated from Atp1a1 heterozygous or Cd36-null mice, we demonstrated that CD36 recruited an Na(+)/K(+) ATPase-Lyn complex for Lyn activation in response to oxLDL. Macrophages deficient in the alpha1 Na(+)/K(+)-ATPase catalytic subunit did not respond to activation of CD36, showing attenuated oxLDL uptake and foam cell formation, and oxLDL failed to inhibit migration of these macrophages. Furthermore, Apoe-null mice, which are a model of atherosclerosis, were protected from diet-induced atherosclerosis by global deletion of a single allele encoding the alpha1 Na(+)/K(+)-ATPase subunit or reconstitution with macrophages that lacked an allele encoding the alpha1 Na(+)/K(+)-ATPase subunit. These findings identify Na(+)/K(+)-ATPase as a potential target for preventing or treating atherosclerosis. PMID- 26350903 TI - Second-hand smoke exposure higher for kids and teens. PMID- 26350902 TI - Identification of potential drug targets for tuberous sclerosis complex by synthetic screens combining CRISPR-based knockouts with RNAi. AB - The tuberous sclerosis complex (TSC) family of tumor suppressors, TSC1 and TSC2, function together in an evolutionarily conserved protein complex that is a point of convergence for major cell signaling pathways that regulate mTOR complex 1 (mTORC1). Mutation or aberrant inhibition of the TSC complex is common in various human tumor syndromes and cancers. The discovery of novel therapeutic strategies to selectively target cells with functional loss of this complex is therefore of clinical relevance to patients with nonmalignant TSC and those with sporadic cancers. We developed a CRISPR-based method to generate homogeneous mutant Drosophila cell lines. By combining TSC1 or TSC2 mutant cell lines with RNAi screens against all kinases and phosphatases, we identified synthetic interactions with TSC1 and TSC2. Individual knockdown of three candidate genes (mRNA-cap, Pitslre, and CycT; orthologs of RNGTT, CDK11, and CCNT1 in humans) reduced the population growth rate of Drosophila cells lacking either TSC1 or TSC2 but not that of wild-type cells. Moreover, individual knockdown of these three genes had similar growth-inhibiting effects in mammalian TSC2-deficient cell lines, including human tumor-derived cells, illustrating the power of this cross-species screening strategy to identify potential drug targets. PMID- 26350904 TI - CMA votes to divest from fossil fuels. PMID- 26350905 TI - Assurance for MDs who refuse to assist in dying. PMID- 26350906 TI - A year of listening, focusing and action. PMID- 26350907 TI - Herpes zoster ophthalmicus complicated by encephalitis. PMID- 26350908 TI - Psychedelic medicine: a re-emerging therapeutic paradigm. PMID- 26350909 TI - Managing isolated head trauma in young children. PMID- 26350910 TI - Parents should declare children's vaccine status, doctors say. PMID- 26350912 TI - First exposure. PMID- 26350911 TI - Derivation and validation of a clinical decision rule to identify young children with skull fracture following isolated head trauma. AB - BACKGROUND: There is no clear consensus regarding radiologic evaluation of head trauma in young children without traumatic brain injury. We conducted a study to develop and validate a clinical decision rule to identify skull fracture in young children with head trauma and no immediate need for head tomography. METHODS: We performed a prospective cohort study in 3 tertiary care emergency departments in the province of Quebec. Participants were children less than 2 years old who had a head trauma and were not at high risk of clinically important traumatic brain injury (Glasgow Coma Scale score < 15, altered level of consciousness or palpable skull fracture). The primary outcome was skull fracture. For each participant, the treating physician completed a standardized report form after physical examination and before radiologic evaluation. The decision to order skull radiography was at the physician's discretion. The clinical decision rule was derived using recursive partitioning. RESULTS: A total of 811 patients (49 with skull fracture) were recruited during the derivation phase. The 2 predictors identified through recursive partitioning were parietal or occipital swelling or hematoma and age less than 2 months. The rule had a sensitivity of 94% (95% confidence interval [CI] 83%-99%) and a specificity of 86% (95% CI 84%-89%) in the derivation phase. During the validation phase, 856 participants (44 with skull fracture) were recruited. The rule had a sensitivity of 89% and a specificity of 87% during this phase. INTERPRETATION: The clinical decision rule developed in this study identified about 90% of skull fractures among young children with mild head trauma who had no immediate indication for head tomography. Use of the rule would have reduced the number of radiologic evaluations by about 60%. PMID- 26350913 TI - CMPA fees will go up - and down. PMID- 26350914 TI - Study boosts vitamin D-multiple sclerosis link. PMID- 26350915 TI - CMA developing assisted death guidelines. PMID- 26350916 TI - Statins decrease the risk of stroke in individuals with heterozygous familial hypercholesterolemia: A systematic review and meta-analysis. AB - BACKGROUND: Familial hypercholesterolemia (FH) is undoubtedly associated with premature coronary heart disease, but it is debatable whether FH increases the risk for stroke. OBJECTIVE: To meta-analyze available evidence regarding the incidence of stroke in individuals with heterozygous (He) FH. METHODS: We conducted a systematic review and a meta-analysis of epidemiological studies, including English-language publications until June 2015; four observational studies, with 3374 participants with HeFH, were included in the analysis. Cerebrovascular disease comprised of ischemic stroke or transient ischemic attack. Since studies did not include any control subjects, the corresponding general population of the same reference area and period of time for each HeFH study served as control group. Analyses were performed according to the period of time during which the studies were conducted: prestatin and statin era (before and after 1987 when lovastatin was launched). RESULTS: In the prestatin era, individuals with HeFH exhibited a higher risk for stroke compared with the general population [odds ratio (OR) = 7.658, 95% confidence interval (CI): 6.059 9.678, p < 0.01]. In contrast, FH subjects had a lower odds for stroke following the generalization of statin therapy (OR = 0.251, 95% CI: 0.176-0.358, p < 0.01). CONCLUSIONS: Taking into account the small number of studies and methodological issues, HeFH was associated with a higher risk of cerebrovascular disease compared with the general population in the prestatin era, which was significantly reduced after the introduction of statin therapy. PMID- 26350917 TI - Mild Hypothermia Combined with Hydrogen Sulfide Treatment During Resuscitation Reduces Hippocampal Neuron Apoptosis Via NR2A, NR2B, and PI3K-Akt Signaling in a Rat Model of Cerebral Ischemia-Reperfusion Injury. AB - We investigated whether mild hypothermia combined with sodium hydrosulfide treatment during resuscitation improves neuron survival following cerebral ischemia-reperfusion injury beyond that observed for the individual treatments. Male Sprague-Dawley rats were divided into seven groups (n = 20 for each group). All rats underwent Pulsinelli 4-vessel occlusion. Ischemia was induced for 15 min using ligatures around the common carotid arteries, except for the sham group. Immediately after initiating reperfusion, the mild hypothermia (MH), sodium hydrosulfide (NaHS), hydroxylamine (HA), MH + NaHS, MH + HA, and ischemia reperfusion (I/R) control groups received an intraperitoneal injection of saline, sodium hydrosulfide, hydroxylamine, sodium hydrosulfide, hydroxylamine, and saline, respectively, and mild hypothermia (32 to 33 degrees C) was induced in the MH, MH + NaHS, and MH + HA groups for 6 h. The levels of NR2A, NR2B, p-Akt, and p-Gsk-3beta in the hippocampus of the MH, NaHS, and MH + NaHS groups were higher than those in the I/R control group, with the highest levels observed in the MH + NaHS group (P < 0.05). Treatment with hydroxylamine reduced the levels of these proteins in the HA and MH + HA groups, compared with the I/R control and MH groups, respectively. The apoptotic index of the CA1 region of the hippocampus was 45.2, 66.5, 63.5, and 84.8 % in the MH + NaHS, MH, NaHS, and I/R control groups, respectively (P < 0.05), indicating that the combination treatment shifted the NR2A/NR2B balance in favor of synaptic neuron stimulation and phosphatidylinositol 3'-kinase (PI3K)/Akt signaling. The combination of mild hypothermia and sodium hydrosulfide treatment for resuscitation following ischemia-reperfusion injury was more beneficial for reducing hippocampal apoptosis and pathology than that of mild hypothermia or hydrogen sulfide treatment alone. PMID- 26350918 TI - Fat-Modified Enteral Formula Improves Feeding Tolerance in Critically Ill Patients: A Multicenter, Single-Blind, Randomized Controlled Trial. AB - BACKGROUND: Improvement of fat digestion and absorption was supposed to relieve feeding intolerance. This trial aimed to evaluate the effect of a fat-modified enteral formula on feeding tolerance in critically ill patients. MATERIALS AND METHODS: This trial was conducted in 7 hospitals in China. In total, 144 intensive care unit (ICU) patients with estimated need of enteral nutrition (EN) for at least 5 days were randomly given fat-modified enteral formula containing medium-chain triglycerides (MCT), carnitine, and taurine (interventional feed group, n = 71) or standard enteral formula (control feed group, n = 73). EN intake, feeding intolerance (diarrhea, vomiting, gastric retention, and abdominal distension) and outcomes (mechanical ventilator-free days of 28 days, length of ICU stay, length of hospital stay, and in-hospital mortality) were collected. RESULTS: Daily calories and protein intake were increased in the interventional feed group compared with the control feed group ( P < .01). Total incidence of feeding intolerance was 42.3% in the interventional feed group and 65.7% in the control feed group ( P < .001). Daily incidence of feeding intolerance was 11.3%, 18.3%, 14.1%, 25.4%, and 26.1% in the interventional feed group and 31.5%, 32.9%, 34.2%, 34.2%, and 30.4% in the control feed group from study days 1-5 ( P = .0083). Incidence of feeding intolerance without abdominal distention was 32.9% in the interventional feed group and 49.3% in the control feed group ( P = .047), while the incidence of abdominal distension was 26.8% in the interventional feed group and 43.8% in the control feed group ( P = .03). No significant differences existed in outcomes between the 2 groups. CONCLUSIONS: The fat-modified enteral formula containing MCT, carnitine, and taurine may improve feeding tolerance in critically ill patients. PMID- 26350919 TI - Crying Without Tears: Dimensions of Crying and Relations With Ocular Dryness and Mental Well-Being in Patients With Sjogren's Syndrome. AB - This study examined dimensions of crying and its relations with ocular dryness and mental well-being in patients with Sjogren's syndrome, a systemic autoimmune disease with dryness as primary symptom. Three-hundred patients with Sjogren's syndrome completed questionnaires on crying, dryness, and well-being. The crying questionnaire revealed four dimensions: "Cryability" (comprising both crying sensibility and ability to cry), Somatic consequences, Frustration, and Suppression. Compared to 100 demographically-matched control participants from the general population, patients scored low on Cryability and high on Somatic consequences and Frustration. The crying dimensions generally showed significant but weak associations with ocular dryness and mental well-being in patients. This is the first quantitative study indicating that crying problems are more common in patients with Sjogren's syndrome than in the general population. Perhaps, patients who experience problems with crying could be helped to rely on other ways of expressing emotions than crying in tear-inducing situations. PMID- 26350920 TI - [Ligament reconstruction in hand surgery]. PMID- 26350921 TI - Wash Your Hands! PMID- 26350922 TI - England's National Health Service--Broke but Not Broken. PMID- 26350923 TI - Public Health and the First Amendment. PMID- 26350924 TI - One Nation, Underinsured. PMID- 26350925 TI - Employer-Sponsored Insurance: Is It Eroding Under the ACA, and Should We Care? PMID- 26350926 TI - Courting Disaster: Environmental Justice and the US Court System. PMID- 26350927 TI - The Future of the World Health Organization: Lessons Learned From Ebola. PMID- 26350928 TI - The Long and Winding Road of Mental Illness Stigma. PMID- 26350929 TI - The Institutional Effects of Incarceration: Spillovers From Criminal Justice to Health Care. AB - POLICY POINTS: The steady increase in incarceration is related to the quality and functioning of the health care system. US states that incarcerate a larger number of people show declines in overall access to and quality of care, rooted in high levels of uninsurance and relatively poor health of former inmates. Providing health care to former inmates would ease the difficulties of inmates and their families. It might also prevent broader adverse spillovers to the health care system. The health care system and the criminal justice system are related in real but underappreciated ways. CONTEXT: This study examines the spillover effects of growth in state-level incarceration rates on the functioning and quality of the US health care system. METHODS: Our multilevel approach first explored cross-sectional individual-level data on health care behavior merged to aggregate state-level data regarding incarceration. We then conducted an entirely aggregate-level analysis to address between-state heterogeneity and trends over time in health care access and utilization. FINDINGS: We found that individuals residing in states with a larger number of former prison inmates have diminished access to care, less access to specialists, less trust in physicians, and less satisfaction with the care they receive. These spillover effects are deep in that they affect even those least likely to be personally affected by incarceration, including the insured, those over 50, women, non-Hispanic whites, and those with incomes far exceeding the federal poverty threshold. These patterns likely reflect the burden of uncompensated care among former inmates, who have both a greater than average need for care and higher than average levels of uninsurance. State-level analyses solidify these claims. Increases in the number of former inmates are associated simultaneously with increases in the percentage of uninsured within a state and increases in emergency room use per capita, both net of controls for between-state heterogeneity. CONCLUSIONS: Our analyses establish an intersection between systems of care and corrections, linked by inadequate financial and administrative mechanisms for delivering services to former inmates. PMID- 26350930 TI - Where Is Buprenorphine Dispensed to Treat Opioid Use Disorders? The Role of Private Offices, Opioid Treatment Programs, and Substance Abuse Treatment Facilities in Urban and Rural Counties. AB - POLICY POINTS: Buprenorphine is an effective opioid dependence treatment that has expanded access to care since its 2002 approval, but it can only be prescribed by physicians waivered to treat a limited number of individuals. We examined the impact of 2006 legislation that increased waivered physician patient limits from 30 to 100 on buprenorphine use, and found that 100-patient-waivered physicians were significantly associated with growth in buprenorphine use, with no such relationship for 30-patient-waivered physicians. Policies relaxing patient limits may be more effective in increasing buprenorphine use than alternatives such as opening new substance abuse treatment facilities or increasing the overall number of waivered physicians. CONTEXT: Opioid use disorders are a significant public health problem. In 2002, the FDA approved buprenorphine as an opioid use disorder treatment when prescribed by waivered physicians who were limited to treating 30 patients at a time. In 2006, federal legislation raised this number to 100 patients. Although federal legislators are considering increasing these limits further and expanding prescribing privileges to nonphysicians, little information is available regarding the impact of such changes on buprenorphine use. We therefore examined the impact of the 2006 legislation-as well as the association between urban and rural waivered physicians, opioid treatment programs, and substance abuse treatment facilities-on buprenorphine distributed per capita over the past decade. METHODS: Using 2004-2011 state-level data on buprenorphine dispensed and county-level data on the number of buprenorphine-waivered physicians and substance abuse treatment facilities using buprenorphine, we estimated a multivariate ordinary least squares regression model with state fixed effects of a state's annual total buprenorphine dispensed per capita as a function of the state's number of buprenorphine providers. FINDINGS: The amount of buprenorphine dispensed has been increasing at a greater rate than the number of buprenorphine providers. The number of physicians waivered to treat 100 patients with buprenorphine in both rural and urban settings was significantly associated with increased amounts of buprenorphine dispensed per capita. There was no significant association in the growth of buprenorphine distributed and the number of physicians with 30-patient waivers. CONCLUSIONS: The greater amounts of buprenorphine dispensed are consistent with the potentially greater use of opioid agonists for opioid use disorder treatment, though they also make their misuse more likely. The changes after the 2006 legislation suggest that policies focused on increasing the number of patients that a single waivered physician could safely and effectively treat could be more effective in increasing buprenorphine use than would alternatives such as opening new substance abuse treatment facilities or raising the overall number of waivered physicians. PMID- 26350931 TI - On the Outskirts of National Health Reform: A Comparative Assessment of Health Insurance and Access to Care in Puerto Rico and the United States. AB - POLICY POINTS: Puerto Rico is the United States' largest territory, home to nearly 4 million American citizens, yet it has remained largely on the outskirts of US health policy, including the Affordable Care Act (ACA). We analyzed national survey data from 2011 to 2012 and found that despite its far poorer population, Puerto Rico outperforms the mainland United States on several measures of health care coverage and access to care. While the ACA significantly increases federal resources in Puerto Rico, ongoing federal restrictions on Medicaid funding and premium tax credits in Puerto Rico pose substantial health policy challenges in the territory. CONTEXT: Puerto Rico is the United States' largest territory, home to nearly 4 million American citizens. Yet it has remained largely on the outskirts of US health policy, including the Affordable Care Act (ACA). This article presents an overview of Puerto Rico's health care system and a comparative analysis of coverage and access to care in Puerto Rico and the mainland United States. METHODS: We analyzed 2011-2012 data from the Behavioral Risk Factor Surveillance System, and 2012 data from the American Community Survey and its counterpart, the Puerto Rico Community Survey. Among adults 18 and older, we examined health insurance coverage; access measures, such as having a usual source of care and cost-related delays in care; self-reported health; and the receipt of recommended preventive services, such as cancer screening and glucose testing. We used multivariate regression models to compare Puerto Rico and the mainland United States, adjusted for age, income, race/ethnicity, and other demographic variables. FINDINGS: Uninsured rates were significantly lower in Puerto Rico (unadjusted 7.4% versus 15.0%, adjusted difference: -12.0%, p < 0.001). Medicaid was far more common in Puerto Rico. Puerto Rican residents were more likely than those in the mainland United States to have a usual source of care and to have had a checkup within the past year, and fewer experienced cost-related delays in care. Screening rates for diabetes, mammograms, and Pap smears were comparable or better in Puerto Rico, while colonoscopy rates were lower. Self-reported health was slightly worse, but obesity and smoking rates were lower. CONCLUSIONS: Despite its far poorer population, Puerto Rico outperforms the mainland United States on several measures of coverage and access. Congressional policies capping federal Medicaid funds to the territory, however, have contributed to major budgetary challenges. While the ACA has significantly increased federal resources in Puerto Rico, ongoing restrictions on Medicaid funding and premium tax credits are posing substantial health policy challenges in the territory. PMID- 26350932 TI - Does Social Capital Explain Community-Level Differences in Organ Donor Designation? AB - POLICY POINTS: The growing shortage of life-saving organs has reached unprecedented levels, with more than 120,000 Americans waiting for them. Despite national attempts to increase organ donation and federal laws mandating the equitable allocation of organs, geographic disparities remain. A better understanding of the contextual determinants of organ donor designation, including social capital, may enhance efforts to increase organ donation by raising the probability of collective action and fostering norms of reciprocity and cooperation while increasing costs to defectors. Because community-level factors, including social capital, predict more than half the variation in donor designation, future interventions should tailor strategies to specific communities as the unit of intervention. CONTEXT: The growing shortage of organs has reached unprecedented levels. Despite national attempts to increase donation and federal laws mandating the equitable allocation of organs, their availability and waiting times vary significantly nationwide. Organ donor designation is a collective action problem in public health, in which the regional organ supply and average waiting times are determined by the willingness of individuals to be listed as organ donors. Social capital increases the probability of collective action by fostering norms of reciprocity and cooperation while increasing costs to defectors. We examine whether social capital and other community-level factors explain geographic variation in organ donor designation rates in Massachusetts. METHODS: We obtained a sample of 3,281,532 registered drivers in 2010 from the Massachusetts Department of Transportation Registry of Motor Vehicles (MassDOT RMV). We then geocoded the registry data, matched them to 4,466 census blocks, and linked them to the 2010 US Census, the American Community Survey (ACS), and other sources to obtain community-level sociodemographic, social capital (residential segregation, voter registration and participation, residential mobility, violent-death rate), and religious characteristics. We used spatial modeling, including lagged variables to account for the effect of adjacent block groups, and multivariate regression analysis to examine the relationship of social capital and community-level characteristics with organ donor designation rates. FINDINGS: Block groups with higher levels of social capital, racial homogeneity, income, workforce participation, owner-occupied housing, native-born residents, and white residents had higher rates of organ donor designation (p < 0.001). These factors remained significant in the multivariate model, which explained more than half the geographic variance in organ donor designation (R(2) = 0.52). CONCLUSIONS: The findings suggest that community-level factors, including social capital, predict more than half the variation in donor designation. Future interventions should target the community as the unit of intervention and should tailor messaging for areas with low social capital. PMID- 26350935 TI - The modern diagnosis and management of pleural effusions. PMID- 26350934 TI - A new digital tool for radiographic bone level measurements in longitudinal studies. AB - BACKGROUND: The reproducibility of measurements on radiographs is influenced by the techniques by which the images as well as the measurements are obtained. Thus, bias resulting from errors in the image and/or image examinations at two points in time may result in wrongful registrations of true biological or pathological changes. The aim of the present study was to propose and evaluate an indirect radiological examination technique, by which bias, when measuring radiographic bone level, could be substantially reduced as compared to the technique using direct mm measurements. METHODS: A plugin to ImageJ was designed to reduce bias when measuring bone loss on radiographic images. In human dry mandibles, radiographic images of 20 teeth were obtained parallel with the tooth axis (alpha = 0) and at an angle of 30 degrees deviation. The direct technique of measuring radiographic bone level (RBL) and the indirect, length-adjusted RBL were registered by four researchers in a double blinded fashion. RESULTS: When mean RBL measured at 0 degrees angle was 7.0 mm, the corresponding mean RBL measured at 30 degrees angle was 7.8 mm, signifying an 11.4% increase (p = 0.032), whereas the mean length-adjusted RBL increased by 0.6% (p = 0.9). CONCLUSIONS: This study showed that the use of the original, direct technique (ImageJ) resulted in markedly biased radiographic bone level at 30 degrees angle, while the proposed indirect length-adjusted technique (ImageJ plugin) did not. PMID- 26350936 TI - General practitioners' relationship with preventive knowledge: a qualitative study. AB - General practitioners (GPs) do not provide enough preventive care. Nonetheless, without a detailed understanding of the logical processes that underlie their practices, it remains difficult to develop effective means of improvement. Their relationship to knowledge is one of three elements that strongly structure GPs' preventive work (together with the doctor-patient relationship and the organisation of their professional space).The objective of this article was to explore the question of GPs' relationship to knowledge about prevention. In 2010 2011, semi-directive interviews with a diverse sample of 100 GPs practising in the Paris metropolitan area were conducted. These interviews were coded according a reading grid that was developed collectively and analysed in the framework of grounded theory. The cognitive universe of GPs is neither homogeneous nor stable. It is composed of biomedical knowledge (delivered via guidelines, the professional press, opinion leaders and pharmaceutical companies), clinical knowledge (fed by individual situations from their daily experience and often conflicting with epidemiologic reasoning and data) and lay knowledge (from folk culture). Plunged into this complex cognitive universe that is difficult for them to master, doctors construct their own idiosyncratic preventive style by themselves, mostly in isolation. Two types of actions emerged as likely to help GPs better appropriate preventive knowledge: clarification of scientific data (especially from epidemiology and the social sciences) but also development of a collective analysis of the cognitive work required to integrate the different types of knowledge mobilised daily in their preventive practices. PMID- 26350937 TI - The Low FODMAP Diet and Its Application in East and Southeast Asia. AB - There is growing interest in using food choice/dietary change to influence clinical outcomes in patients with irritable bowel syndrome (IBS). The low fermentable oligo-, di-, mono-saccharides, and polyols (FODMAPs) diet is an evidence-based approach that is gaining popularity in many Western countries. The low FODMAP diet is based on restricting dietary intake of short chain carbohydrates that are slowly absorbed or indigestible and not absorbed during passage through the small intestine. These are collectively described as "FODMAPs" and comprise oligosaccharides (mostly fructans, galacto oligosaccharides), sugar polyols, fructose in excess of glucose, and lactose in lactose malabsorbers. The general strategy of the diet is to avoid foods high in FODMAPs and replace them with foods low in FODMAPs, with long-term restriction limited to what is required to control symptoms. The likely mechanism of action is minimisation of the stimulation of mechanoreceptors exerted by distension of the intestinal lumen with water from osmotic effects and gases from bacterial fermentation in those with visceral hypersensitivity. The success of this dietary approach greatly depends on detailed knowledge about the FODMAP composition of food com - monly consumed in that country. While the content of foods associated with East and Southeast Asian cuisines has not been fully explored, major high FODMAP sources are frequently used and include onion, garlic, shallots, legumes/pulses, and wheat-based products. Thus, this dietary approach holds great promise in treating IBS patients in East and Southeast Asia. The aim of this review is to highlight how the diet is implemented, its efficacy, and troublesome ingredients frequently used in Asian dishes. PMID- 26350938 TI - Validity and Reliability of the Japanese Version of the Rome III Diagnostic Questionnaire for Irritable Bowel Syndrome and Functional Dyspepsia. AB - BACKGROUND/AIMS: Reliable diagnostic instruments for measuring the presence of functional gastrointestinal disorders based on the Rome III criteria have been lacking in Japan. The aims of the present study were to translate and validate the Rome III diagnostic questionnaire which was widely used in Western countries. METHODS: The original version of Rome III diagnostic questionnaire was translated from English into Japanese through 3 independent forward translations, resolution, back translation and reconciliation of the differences. Forty-nine patients with irritable bowel syndrome (IBS), 32 patients with functional dyspepsia (FD) and 56 subjects without any current GI symptoms as controls were recruited from three hospitals located in different regions of Japan and completed the IBS and FD diagnostic modules twice within 14 days. Kappa statistic was used to assess test-retest reliability. The sensitivity and specificity of each diagnostic module for distinguishing IBS or FD patients from controls was tested. RESULTS: Median kappa statistics were 0.63 for the translated IBS diagnostic module and 0.68 for the FD module. The sensitivity, specificity, and positive predict value of the IBS module against physician diagnosis was 61.2%, 100%, and 100% and those of the FD module was 53.2%, 98.2%, and 94.4%, respectively. Meanwhile, IBS patients were significantly more likely to report blood in stools compared to controls (18.4% vs 1.8%, P < 0.01). CONCLUSIONS: The IBS and FD diagnostic modules on the Japanese version of the Rome III diagnostic questionnaire are valid and reliable. Further studies are warranted to elucidate the diagnostic utility of the red flag questionnaire. PMID- 26350939 TI - Development of a Vision-assisted Manometry Catheter for High-resolution Esophageal Manometry. AB - High-resolution esophageal manometry is becoming a standard diagnostic method for esophageal motility disorders. High-resolution manometry catheters are inserted blindly, which sometimes results in coiling in the esophagus and failure to cross the crural diaphragm in patients with large hiatal hernias. The newly developed manometry catheter described in this report has an optical module in front of the catheter that provides forward images during insertion and prevents coiling and malplacement of the catheter. This case report describes the composition of a new manometry catheter with an optical module and shows that the new catheter functions well in both in vitro and in vivo settings. The new manometry catheter will help guide the right way and prevent coiling in the esophagus. PMID- 26350940 TI - Chiral SiO2 and Ag@SiO2 Materials Templated by Complexes Consisting of Comblike Polyethyleneimine and Tartaric Acid. AB - A facile avenue to fabricate micrometer-sized chiral (L-, D-) and meso-like (dl-) SiO2 materials with unique structures by using crystalline complexes (cPEI/tart), composed of comblike polyethyleneimine (cPEI) and L-, D-, or dl-tartaric acid, respectively, as catalytic templates is reported. Interestingly, both chiral crystalline complexes appeared as regularly left- and right-twisted bundle structures about 10 MUm in length and about 5 MUm in diameter, whereas the dl form occurred as circular structures with about 10 MUm diameter. Subsequently, SiO2 @cPEI/tart hybrids with high silica content (>55.0 wt %) were prepared by stirring a mixture containing tetramethoxysilane (TMOS) and the aggregates of the crystalline complexes in water. The chiral SiO2 hybrids and calcined chiral SiO2 showed very strong CD signals and a nanofiber-based morphology on their surface, whereas dl-SiO2 showed no CD activity and a nanosheet-packed disklike shape. Furthermore, metallic silver nanoparticles (Ag NPs) were encapsulated in each silica hybrid to obtain chiral (D and L forms) and meso-like (dl form) Ag@SiO2 composites. Also, the reaction between L-cysteine (Lcys) and these Ag@SiO2 composites was preliminarily investigated. Only chiral L- and D-Ag@SiO2 composites promoted the reaction between Lcys and Ag NPs to produce a molecular [Ag-Lcys]n complex with remarkable exciton chirality, whereas the reaction hardly occurred in the case of meso-like (dl-) Ag@SiO2 composite. PMID- 26350941 TI - Functional mechanics of beetle mandibles: Honest signaling in a sexually selected system. AB - Male stag beetles possess colossal mandibles, which they wield in combat to obtain access to females. As with many other sexually selected weapons, males with longer mandibles win more fights. However, variation in the functional morphology of these structures, used in male-male combat, is less well understood. In this study, mandible bite force, gape, structural strength, and potential tradeoffs are examined across a wide size range for one species of stag beetle, Cyclommatus metallifer. We found that not only does male mandible size demonstrate steep positive allometry, but the shape, relative bite force, relative gape, and safety factor of the mandibles also change with male size. Allometry in these functionally important mandibular traits suggests that larger males with larger mandibles should be better fighters, and that the mandibles can be considered an honest signal of male fighting ability. However, negative allometry in mandible structural safety factor, wing size, and flight muscle mass suggest significant costs and a possible limit on the size of the mandibles. J. Exp. Zool. 325A:3-12, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26350942 TI - The addition of synchronous whole-body vibration to battling rope exercise increases skeletal muscle activity. AB - OBJECTIVES: To evaluate the effects of performing battling rope exercise with and without the addition of whole-body vibration (WBV) on muscle activity of the leg, trunk, and upper body. METHODS: Twenty-eight recreationally active university students completed 20-s of battling rope undulation for 6 separate conditions: 1) alternating arm motion no WBV -Alt_NoWBV; 2) alternating arm motion 30 Hz low amplitude WBV -Alt_30 Hz-L; 3) alternating arm motion 50 Hz high amplitude Alt_50 Hz-H; 4) double arm motion no WBV -Double_NoWBV; 5) double arm motion 30Hz low amplitude WBV -Double_30Hz-L; 6) double arm motion 50 'Hz high amplitude Double_50 Hz-H. Electromyography (EMG) was measured for the gastrocnemius medialis (GM), vastus medialis oblique (VMO), vastus lateralis (VL), rectus abdominis (RA), multifidus (MF), biceps brachii (BB), and triceps brachii (TB) muscles. RESULTS: The double arm motion during undulation resulted in greater (p<0.05) muscle activity in the VMO, VL, RA, and MF muscles while the GM was more active during the alternating arm motion. WBV at 50Hz increased EMG in all muscles measured vs NoWBV and the 30 Hz condition. CONCLUSION: These results are the first to demonstrate that the exercise stimulus of performing battling rope exercise can be augmented by completing the exercise while being exposed to WBV from a ground-based platform. PMID- 26350943 TI - Mechanography performance tests and their association with sarcopenia, falls and impairment in the activities of daily living - a pilot cross-sectional study in 293 older adults. AB - OBJECTIVES: Muscle mass and muscle power considerably decline with aging. The aim of the present study was to determine the association between muscular function using mechanography and sarcopenia, falls and impairment in the activities of daily living (ADL) in a sample of 293 community-dwelling women and men aged 60-85 years in Berlin, Germany. METHODS: Muscle function was determined by muscle power per body mass in vertical countermovement jumps (2LJPrel) and the chair rising test (CRTPrel) on a force plate. Sarcopenia status was assessed by estimating appendicular muscle mass with dual-X-ray absorptiometry. Self-reported ADL impairment and falls in the last 12 months were determined. RESULTS: ADL impairment was significantly correlated with all performance tests but not with muscle mass. The 2LJPrel (OR 0.88, 95%-CI 0.79-0.98), the Esslinger Fitness Index (EFI) (OR 0.97, 95%-CI 0.94-1.00) and the maximal velocity of the CRT (OR 0.70, 95%-CI 0.53-0.93) remained significant correlates for sarcopenia independent of age in men but not in women. The EFI could differentiate female individuals who had past fall events (OR 0.96, 95%-CI 0.93-0.98). CONCLUSION: The results of the present study highlight the importance of assessing muscle power in older individuals as a relevant correlate for functional decline. PMID- 26350944 TI - Reliability of parameters during stair ascent measured with Leonardo Mechanograph((r)) Stair A in healthy subjects. AB - OBJECTIVES: Stair climbing (SC) as daily activity is assessed with different SC tests, but none directly measures ground reaction force over several steps. The Leonardo Mechanograph Stair A has five steps and four force sensors. This study aimed at investigating the reliability of the Stair A test for force, power and time to SC. METHODS: 55 healthy participants (age: 48+/-14 years) were five times tested during SC with self-chosen and fast speed. 30 participants were examined for test-retest-reliability, calculated with the intraclass correlation coefficient (ICC). The variability was examined with the coefficient of variation (CV). To determine potential associations between SC and jumping performance or daily activity, squat and countermovement jumps were additionally performed and the International physical activity questionnaire (IPAQ) was completed. RESULTS: The inter-visit ICCs of self-chosen and fast SC were good to excellent 0.63-0.77. The intra-visit ICCs were excellent after three trials (0.78-0.88). The CVs for SC with self-chosen speed were lower (2.1-6.6%) than those for fast SC (4.9 10.8%). There were no significant correlations between SC and jump parameters and only moderate correlations with the IPAQ. CONCLUSION: The Stair A is a reliable tool for the assessment of SC. PMID- 26350945 TI - Alpine skiing is associated with higher femoral neck bone mineral density. AB - OBJECTIVE: To evaluate the influence of elite-level alpine skiing on athletes' skeleton. METHODS: Thirteen professional alpine skiers (9 males and 4 females with mean age of 22.6 years) and their age- and height matched control subjects were measured with dual energy X-ray absorptiometry (total body, lumbar spine, proximal femur, forearm) and quantitative ultrasound (hand). RESULTS: After adjusting for sex, age, weight and height, between-group differences were 15% (p=0.012) for the lumbar spine, 14% (p=0.022) for the femoral neck, 10% (p=0.051) for the total hip, and 11% (p=0.001) for the total body favoring the alpine skiers. However, after controlling for total body lean mass (~muscle mass), the group-differences lost their statistical significance, the borderline 10% difference (p=0.051) in femoral neck BMD excluded. CONCLUSION: Factors contributing to the alpine skiers' higher BMD may not only include the greater muscle mass (~stronger muscles) of these athletes but also a large number of impacts and possibly other high-frequency features in external loading generated by the high-speed skiing performance. PMID- 26350946 TI - Effect of electrical stimulation-induced muscle force and streptomycin treatment on muscle and trabecular bone mass in early-stage disuse musculoskeletal atrophy. AB - OBJECTIVES: The aim was to determine whether daily muscle electrical stimulation (ES) and streptomycin treatment would have positive or negative effects on trabecular bone mass in disuse rats. METHODS: Seven-week-old male F344 rats were randomly divided into five groups of eight animals each: an age-matched control group (CON); a sciatic denervation group (DN); a DN + direct electrical stimulation group (DN+ES); a DN + streptomycin treatment group (DN+SM); and a DN+ES+SM group. The tibialis anterior (TA) muscles in all ES groups were stimulated with 16mA at 10Hz for 30 min/day, six days/week, for one week. Bone volume and structure were evaluated using micro-CT, and histological examinations of the tibiae were performed. RESULTS: Direct ES significantly reduced the disuse induced trabecular bone loss. Osteoid thickness were also significantly greater in the ES groups than in the DN group. Micro CT and histomorphological parameters were significantly lower in the DN+ES+SM group than in the DN+ES group, while there were no significant differences between the DN and DN+SM groups. CONCLUSIONS: These results suggest that ES-induced muscle force reduced trabecular bone loss, and streptomycin treatment did not induce bone loss, but attenuated the effects of ES-induced muscle force on reducing the loss of disused bone. PMID- 26350947 TI - Association between long-term exercise loading and lumbar spine trabecular bone score (TBS) in different exercise loading groups. AB - OBJECTIVE: To examine whether different exercise loading is associated with lumbar vertebral texture as assessed with Trabecular Bone Score (TBS). METHODS: Data from 88 Finnish female athletes and 19 habitually active women (reference group) were analyzed. Participants' mean age was 24.3 years (range 17-40 years). Athletes were divided into five specific exercise loading groups according to sport-specific training history: high-impact (triple jumpers and high jumpers), odd-impact (soccer players and squash players), high-magnitude (power lifters), repetitive impact (endurance runners), and repetitive non-impact (swimmers). TBS values were determined from lumbar vertebral L1-L4 DXA images. Body weight and height, fat-%, lean mass, isometric maximal leg press force, dynamic peak jumping force and lumbar BMD were also measured. RESULTS: Endurance runners' mean TBS value differed significantly from all other groups being about 6% lower than in the reference group. After controlling for body height, isometric leg press force and fat-%, the variables found consistently explaining TBS, the observed between group difference remained significant (B=-0.072, p=0.020). After controlling for BMD, the difference persisted (B=-0.065, p=0.016). There were no other significant adjusted between-group differences. CONCLUSION: Exercise loading history comprising several repeated moderate impacts is associated with somewhat lower TBS, which may indicate specific lumbar microarchitecture in endurance runners. PMID- 26350948 TI - Human muscle signaling responses to 3-day head-out dry immersion. AB - To date little is known about catabolic NO-dependent signaling systems in human skeletal muscle during early stages of gravitational unloading. The goal of the study was to analyze signaling pathways that determine the initial development of proteolytic events in human soleus muscle during short-term gravitational unloading (simulated microgravity). Gravitational unloading was simulated by 3 day head-out dry immersion. Before and after the immersion the samples of soleus muscle were taken under local anesthesia, using biopsy technique. The content of desmin, IRS-1, phospho-AMPK, total and phospho-nNOS in soleus of 6 healthy men was determined using Western-blotting before and after the dry-immersion. Three days of the dry immersion resulted in a significant decrease in desmin, phospho nNOS and phospho-AMPK as compared to the pre-immersion values. The results of the study suggest that proteolytic processes in human soleus at the early stage of gravitational unloading are associated with inactivation of nNOS. Reduction in AMPK phosphorylation could serve as a trigger event for the development of primary atrophic changes in skeletal muscle. PMID- 26350949 TI - Loss and re-adaptation of lumbar intervertebral disc water signal intensity after prolonged bedrest. AB - The adaptation and re-adaptation process of the intervertebral disc (IVD) to prolonged bedrest is important for understanding IVD physiology and IVD herniations in astronauts. Little information is available on changes in IVD composition. In this study, 24 male subjects underwent 60-day bedrest and In/Out Phase magnetic resonance imaging sequences were performed to evaluate IVD shape and water signal intensity. Scanning was performed before bedrest (baseline), twice during bedrest, and three, six and twenty-four months after bedrest. Area, signal intensity, average height, and anteroposterior diameter of the lumbar L3/4 and L4/5 IVDs were measured. At the end of bedrest, disc height and area were significantly increased with no change in water signal intensity. After bedrest, we observed reduced IVD signal intensity three months (p=0.004 versus baseline), six months (p=0.003 versus baseline), but not twenty-four months (p=0.25 versus baseline) post-bedrest. At these same time points post-bedrest, IVD height and area remained increased. The reduced lumbar IVD water signal intensity in the first months after bedrest implies a reduction of glycosaminoglycans and/or free water in the IVD. Subsequently, at two years after bedrest, IVD hydration status returned towards pre-bedrest levels, suggesting a gradual, but slow, re adaptation process of the IVD after prolonged bedrest. PMID- 26350950 TI - IL2RA is associated with persistence of rheumatoid arthritis. AB - INTRODUCTION: Although rheumatoid arthritis (RA) is generally a chronic disease, a proportion of RA-patients achieve disease-modifying antirheumatic drug (DMARD) free sustained remission, reflecting loss of disease-persistence. To explore mechanisms underlying RA-persistence, we performed a candidate gene study. We hypothesized that variants associating with lack of radiographic progression also associate with DMARD-free sustained remission. METHODS: 645 Dutch RA-patients were studied on DMARD-free sustained remission during a maximal follow-up duration of 10-years. Variants associated with radiographic progression under an additive model in the total RA-population (Human Leukocyte Antigens (HLA)-DRB1 shared epitope (SE), Dickkopf-1 (DKK1)-rs1896368, DKK1-rs1896367, DKK1-rs1528873, C5Orf30-rs26232, Interleukin-2 receptor-alpha (IL2RA)-rs2104286, Matrix metalloproteinase-9 (MMP-9)-rs11908352, rs451066 and Osteoprotegerin (OPG) rs1485305) were studied. Cox-regression analyses were performed and Bonferroni correction applied. Soluble IL2Ralpha (sIL2Ralpha)-levels were studied. For replication, 622 RA-patients included in the French Evaluation et Suivi de POlyarthrites Indifferenciees Recentes cohort (ESPOIR)-cohort were investigated. Results were combined in inverse-variance weighted meta-analysis. RESULTS: Similar as previously reported, the SE-alleles associated with less remission (hazard ratio (HR) = 0.57, 95 % confidence interval (95 % CI) = 0.42-0.77, p = 2.72*10(-4)). Variants in DKK-1, C5orf30, MMP-9 and OPG were not associated with remission. The IL2RA-rs2104286 minor allele associated with a higher chance on remission (HR = 1.52, 95 % CI = 1.16-1.99, p = 2.44*10(-3)). The rs2104286 minor allele associated with lower sIL2Ralpha-levels (p = 1.44*10(-3)); lower sIL2Ralpha-levels associated with a higher chance on remission (HR per 100 pg/L = 0.81, 95 % CI = 0.68-0.95, p = 0.012). When including rs2104286 and sIL2Ralpha levels in one analysis, the HR for rs2104286 was 2.27 (95 % CI = 1.06-4.84, p = 0.034) and for sIL2Ralpha 0.83 (95 % CI = 0.70-0.98, p = 0.026). Within ESPOIR, the HR of rs2104286 was 1.31 (95 % CI = 0.90-1.90). The meta-analysis revealed a p-value of 1.01*10(-3). CONCLUSION: IL2RA-rs2104286 and sIL2Ralpha-level associated with RA-persistence. IL2RA variants are known to protect against multiple sclerosis, diabetes mellitus and RA. Besides HLA-SE, IL2RA-rs2104286 is thus far the only known genetic variant associated with both joint destruction and RA-persistence. This underlines the relevance of IL2RA for RA. PMID- 26350951 TI - Irrational choice and the value of information. AB - Irrational decision making in humans and other species challenges the use of optimality in behavioural biology. Here we show that such observations are in fact powerful tools to understand the adaptive significance of behavioural mechanisms. We presented starlings choices between probabilistic alternatives, receiving or not information about forthcoming, delayed outcomes after their choices. Subjects could not use this information to alter the outcomes. Paradoxically, outcome information induced loss-causing preference for the lower probability option. The effect depended on time under uncertainty: information given just after each choice caused strong preference for lower probability, but information just before the outcome did not. A foraging analysis shows that these preferences would maximize gains if post-choice information were usable, as when predators abandon a chase when sure of the prey escaping. Our study illustrates how experimentally induced irrational behaviour supports rather than weakens the evolutionary optimality approach to animal behaviour. PMID- 26350952 TI - Involvement of indirectly allostimulated CD4+CD43highCD45RO+ T cell proliferation in the development of chronic allograft nephropathy. AB - The goal of this study was to identify immunological markers for use in antigen specific assays that predict long-term survival after renal allograft and distinguish stable-functioning (SP) patients from poorly functioning (PP) patients. For this prospective study, 20 patients were enrolled. Eight SP and six PP patients were enrolled in this study. Serum cytokine/chemokine levels were analyzed by the Luminex multiplex assay. To detect indirect alloreactive T cells, we performed indirect mixed lymphocyte reaction using donor-antigen-pulsed autologous dendritic cells as stimulators. Serum induced protein-10 levels were significantly higher in the serum of PP patients, whereas sCD40L levels were higher in SP patients. The PP patients had significantly higher numbers of donor specific CD4(+)CD43(high)CD45RO(+) T cells after indirect allostimulation, whereas this cell population was unchanged in SP patients. The donor-specific CD4(+)CD43(high)CD45RO(+) T cells had the effector memory T cell phenotype. Prospectively, we studied whether these cells influence graft outcome and found that their strong proliferation in pre-transplant patients is related to a poorly functioning graft. Indirectly allostimulated CD4(+)CD43(high)CD45RO(+) T cells may not only contribute to chronic allograft nephropathy development but may also have a role in the progression of acute rejection. Thus, these cells may have potential use as immune-monitoring markers in a noninvasive in vitro assay that predicts graft outcome. PMID- 26350953 TI - Hypoxia promotes apoptosis of neuronal cells through hypoxia-inducible factor 1alpha-microRNA-204-B-cell lymphoma-2 pathway. AB - Neuronal cells are highly sensitive to hypoxia and may be subjected to apoptosis when exposed to hypoxia. Several apoptosis-related genes and miRNAs involve in hypoxia-induced apoptosis. This study aimed to examine the role of HIF1alpha-miR 204-BCL-2 pathway in hypoxia-induced apoptosis in neuronal cells. Annexin V/propidium iodide assay was performed to analyze cell apoptosis in AGE1.HN and PC12 cells under hypoxic or normoxic conditions. The expression of BCL-2 and miR 204 were determined by Western blot and qRT-PCR. The effects of miR-204 overexpression or knockdown on the expression of BCL-2 were evaluated by luciferase assay and Western blot under hypoxic or normoxic conditions. HIF 1alpha inhibitor YC-1 and siHIF-1alpha were employed to determine the effect of HIF-1alpha on the up-regulation of miR-204 and down-regulation of BCL-2 induced by hypoxia. Apoptosis assay showed the presence of apoptosis induced by hypoxia in neuronal cells. Moreover, we found that hypoxia significantly down-regulated the expression of BCL-2, and increased the mRNA level of miR-204 in neuronal cells than that in control. Bioinformatic analysis and luciferase reporter assay demonstrated that miR-204 directly targeted and regulated the expression of BCL 2. Specifically, the expression of BCL-2 was inhibited by miR-204 mimic and enhanced by miR-204 inhibitor. Furthermore, we detected that hypoxia induced cell apoptosis via HIF-1alpha/miR-204/BCL-2 in neuronal cells. This study demonstrated that HIF-1alpha-miR-204-BCL-2 pathway contributed to apoptosis of neuronal cells induced by hypoxia, which could potentially be exploited to prevent spinal cord ischemia-reperfusion injury. PMID- 26350954 TI - Neurofunctional topography of the human hippocampus. AB - Much of what was assumed about the functional topography of the hippocampus was derived from a single case study over half a century ago. Given advances in the imaging sciences, a new era of discovery is underway, with potential to transform the understanding of healthy processing as well as the ability to treat disorders. Coactivation-based parcellation, a meta-analytic approach, and ultra high field, high-resolution functional and structural neuroimaging to characterize the neurofunctional topography of the hippocampus was employed. Data revealed strong support for an evolutionarily preserved topography along the long axis. Specifically, the left hippocampus was segmented into three distinct clusters: an emotional processing cluster supported by structural and functional connectivity to the amygdala and parahippocampal gyrus, a cognitive operations cluster, with functional connectivity to the anterior cingulate and inferior frontal gyrus, and a posterior perceptual cluster with distinct structural connectivity patterns to the occipital lobe coupled with functional connectivity to the precuneus and angular gyrus. The right hippocampal segmentation was more ambiguous, with plausible 2- and 5-cluster solutions. Segmentations shared connectivity with brain regions known to support the correlated processes. This represented the first neurofunctional topographic model of the hippocampus using a robust, bias-free, multimodal approach. PMID- 26350955 TI - In-parallel comparative evaluation between multiparametric magnetic resonance imaging, prostate cancer antigen 3 and the prostate health index in predicting pathologically confirmed significant prostate cancer in men eligible for active surveillance. AB - OBJECTIVE: To assess the performance capabilities of multiparametric magnetic resonance imaging (mpMRI), the prostate health index (PHI) and prostate cancer antigen 3 (PCA3) in predicting the presence of pathologically confirmed significant prostate cancer (PCSPCa), according to the European Randomized Study of Screening Prostate Cancer definition, in a single cohort of patients who underwent radical prostatectomy (RP) but who were eligible for active surveillance (AS). MATERIALS AND METHODS: An observational retrospective study was performed in 120 patients with prostate cancer (PCa), treated with robot assisted RP but eligible for AS according to Prostate Cancer Research International: Active Surveillance criteria. Blood and urine specimens were collected before initial prostate biopsy for PHI and PCA3 measurements, respectively. In addition, all patients underwent mpMRI, preoperatively and 6-8 weeks after biopsy, with a 1.5T scanner using a four-to-five-channel phase array coil combined with an endorectal coin. mpMRI images were assessed and diagrams showing the prostate sextants were used to designate regions of abnormality within the prostate. Prostate findings were assigned to one of five categories according to Prostate Imaging-Reporting and Data System guidelines (PI-RADS) and considered positive for PCa if final PI-RADS score was >3 and negative if <=3. RESULTS: Pathologically confirmed reclassification was observed in 55 patients (45.8%). mpMRI showed good specificity and negative predictive value (0.61 and 0.73, respectively) for excluding PCSPCa compared with the PHI and PCA3. On multivariate analyses and after 1 000 bootstrapping resampling, the inclusion of both mpMRI and the PHI significantly increased the accuracy of the base model in predicting PCSPCa. For the prediction of PCSPCa, in particular, the base model had an area under the curve (AUC) of 0.71 which significantly increased by 4% with the addition of the PHI (AUC = 0.75; P < 0.01) and by 7% with the addition of mpMRI (AUC = 0.78; P < 0.01). Decision-curve analysis showed that the multivariable model with mpMRI had the highest net benefit. CONCLUSION: In a single cohort of patients who underwent RP but who were eligible for AS, mpMRI and, to a lesser extent, the PHI, had an important role in discriminating the presence of PCSPCa; both measures could therefore be useful in the selection and monitoring of patients undergoing AS. PMID- 26350956 TI - SuFEx on the Surface: A Flexible Platform for Postpolymerization Modification of Polymer Brushes. AB - Polymer brushes present a unique architecture for tailoring surface functionalities due to their distinctive physicochemical properties. However, the polymerization chemistries used to grow brushes place limitations on the monomers that can be grown directly from the surface. Several forms of click chemistry have previously been used to modify polymer brushes by postpolymerization modification with high efficiency, however, it is usually difficult to include the unprotected moieties in the original monomer. We present the use of a new form of click chemistry known as SuFEx (sulfur(VI) fluoride exchange), which allows a silyl ether to be rapidly and quantitatively clicked to a polymer brush grown by free-radical polymerization containing native -SO2F groups with rapid pseudo-first-order rates as high as 0.04 s(-1). Furthermore, we demonstrate the use of SuFEx to facilely add a variety of other chemical functional groups to brush substrates that have highly useful and orthogonal reactivity, including alkynes, thiols, and dienes. PMID- 26350957 TI - Together Achieving More: Primary Care Team Communication and Alcohol-Related Healthcare Utilization and Costs. AB - BACKGROUND: Identifying and engaging excessive alcohol users in primary care may be an effective way to improve patient health outcomes, reduce alcohol-related acute care events, and lower costs. Little is known about what structures of primary care team communication are associated with alcohol-related patient outcomes. METHODS: Using a sociometric survey of primary care clinic communication, this study evaluated the relation between team communication networks and alcohol-related utilization of care and costs. Between May 2013 and December 2013, a total of 155 healthcare employees at 6 primary care clinics participated in a survey on team communication. Three-level hierarchical modeling evaluated the link between connectedness within the care team and the number of alcohol-related emergency department visits, hospital days, and associated medical care costs in the past 12 months for each team's primary care patient panel. RESULTS: Teams (n = 31) whose registered nurses displayed more strong (at least daily) face-to-face ties and strong (at least daily) electronic communication ties had 10% fewer alcohol-related hospital days (rate ratio [RR] = 0.90; 95% confidence interval [CI]: 0.84, 0.97). Furthermore, in an average team size of 19, each additional team member with strong interaction ties across the whole team was associated with $1,030 (95% CI: -$1,819, -$241) lower alcohol related patient healthcare costs per 1,000 team patients in the past 12 months. Conversely, teams whose primary care practitioner (PCP) had more strong face-to face communication ties and more weak (weekly or several times a week) electronic communication ties had 12% more alcohol-related hospital days (RR = 1.12; 95% CI: 1.03, 1.23) and $1,428 (95% CI: $378, $2,478) higher alcohol-related healthcare costs per 1,000 patients in the past 12 months. The analyses controlled for patient age, gender, insurance, and comorbidity diagnoses. CONCLUSIONS: Excessive alcohol-using patients may fair better if cared for by teams whose face-to-face and electronic communication networks include more team members and whose communication to the PCP has been streamlined to fewer team members. PMID- 26350958 TI - An Updated Meta-Analysis of Laparoscopic Versus Open Repair for Perforated Peptic Ulcer. AB - Laparoscopic repair (LR) for perforated peptic ulcer (PPU) has been introduced since 1990. Although many studies comparing LR with open repair (OR) have been published, controversy remains regarding the clinical utility of laparoscopic techniques for the treatment of PPU. Thus, it is necessary for us to broaden our knowledge on this subject with the newly published articles. Twenty-four nonrandomized controlled studies (NRS) and five randomized controlled trails (RCTs) were included in our meta-analyses, which comprised 5,268 patients (1,890 in the LR group and 3,378 in the OR group). In the analysis of high quality NRS and RCTs, compared with OR, high quality evidence suggested that LR was associated with a lower incidence of overall postoperative complications; moderate evidence showed that the two procedures had the similar reoperation rate; based on the low quality evidence, LR had reduced hospital mortality and similar operative time; Moreover, LR was observed having the advantages of earlier resumption of oral intake, shorter hospital stay and less analgesic use, which were supported by very low evidence. All the evidences suggest that LR is better than OR for PPU, but more high-quality RCTs are still needed for further validation. PMID- 26350960 TI - Stem Cells in Teeth and Craniofacial Bones. AB - Stem cells are remarkable, and stem cell-based tissue engineering is an emerging field of biomedical science aiming to restore damaged tissue or organs. In dentistry and reconstructive facial surgery, it is of great interest to restore lost teeth or craniofacial bone defects using stem cell-mediated therapy. In the craniofacial region, various stem cell populations have been identified with regeneration potential. In this review, we provide an overview of the current knowledge concerning the various types of tooth- and craniofacial bone-related stem cells and discuss their in vivo identities and regulating mechanisms. PMID- 26350961 TI - Dual Role of Cyanidin-3-glucoside on the Differentiation of Bone Cells. AB - Cyanidin-3-glucoside (C3G) is one of the major components of anthocyanin, a water soluble phytochemical. Recent studies demonstrated the chemopreventive and chemotherapeutic activities of C3G in various conditions, including cancer, although the precise effects of C3G on osteoclast and osteoblast differentiation remain unclear. Here, we investigated the role of C3G in the differentiation of bone-associated cells and its underlying mechanism. C3G inhibited receptor activator of nuclear factor kappa-B ligand (RANKL)-mediated osteoclast differentiation and formation in a dose-dependent manner and downregulated the expression of osteoclast differentiation marker genes. Pretreatment with C3G considerably reduced the induction of extracellular signal-regulated kinase, c Jun N-terminal kinase, and p38 mitogen-activated kinases activation by RANKL in osteoclast precursor cells. Furthermore, C3G dramatically inhibited the expression of c-Fos and nuclear factor of activated T-cells, cytoplasmic 1, which are important transcription factors for osteoclast differentiation and activation. The formation of osteoclasts in coculture of bone marrow cells and calvaria-derived osteoblasts was also inhibited by C3G treatment, although the expression of macrophage colony-stimulating factor and RANKL (master factors for osteoclast differentiation and formation) and osteoprotegerin (a decoy receptor for RANKL) on osteoblasts was unaffected. The inhibitory effect of C3G on osteoclastogenesis is therefore targeted specifically to osteoclasts but not osteoblasts. Moreover, analysis of the expression levels of osteoblast differentiation marker genes and alizarin red staining showed that osteoblast differentiation and matrix formation increased after C3G treatment. Taken together, these results strongly suggest that C3G has a dual role in bone metabolism, as an effective inhibitor of osteoclast differentiation but also as an activator of osteoblast differentiation. Therefore, C3G may be used as a potent preventive or therapeutic agent for bone-related diseases, such as osteoporosis, rheumatoid arthritis, and periodontitis. PMID- 26350962 TI - The interactions between a small molecule and G-quadruplexes are visualized by fluorescence lifetime imaging microscopy. AB - Guanine-rich oligonucleotides can fold into quadruple-stranded helical structures known as G-quadruplexes. Mounting experimental evidence has gathered suggesting that these non-canonical nucleic acid structures form in vivo and play essential biological roles. However, to date, there are no small-molecule optical probes to image G-quadruplexes in live cells. Herein, we report the design and development of a small fluorescent molecule, which can be used as an optical probe for G quadruplexes. We demonstrate that the fluorescence lifetime of this new probe changes considerably upon interaction with different nucleic acid topologies. Specifically, longer fluorescence lifetimes are observed in vitro for G quadruplexes than for double- and single-stranded nucleic acids. Cellular studies confirm that this molecule is cell permeable, has low cytotoxicity and localizes primarily in the cell nucleus. Furthermore, using fluorescence lifetime imaging microscopy, live-cell imaging suggests that the probe can be used to study the interaction of small molecules with G-quadruplexes in vivo. PMID- 26350963 TI - Transcriptome Profiling of the Endophyte Burkholderia phytofirmans PsJN Indicates Sensing of the Plant Environment and Drought Stress. AB - It is widely accepted that bacterial endophytes actively colonize plants, interact with their host, and frequently show beneficial effects on plant growth and health. However, the mechanisms of plant-endophyte communication and bacterial adaption to the plant environment are still poorly understood. Here, whole-transcriptome sequencing of B. phytofirmans PsJN colonizing potato (Solanum tuberosum L.) plants was used to analyze in planta gene activity and the response of strain PsJN to plant stress. The transcriptome of PsJN colonizing in vitro potato plants showed a broad array of functionalities encoded in the genome of strain PsJN. Transcripts upregulated in response to plant drought stress were mainly involved in transcriptional regulation, cellular homeostasis, and the detoxification of reactive oxygen species, indicating an oxidative stress response in PsJN. Genes with modulated expression included genes for extracytoplasmatic function (ECF) group IV sigma factors. These cell surface signaling elements allow bacteria to sense changing environmental conditions and to adjust their metabolism accordingly. TaqMan quantitative PCR (TaqMan-qPCR) was performed to identify ECF sigma factors in PsJN that were activated in response to plant stress. Six ECF sigma factor genes were expressed in PsJN colonizing potato plants. The expression of one ECF sigma factor was upregulated whereas that of another one was downregulated in a plant genotype-specific manner when the plants were stressed. Collectively, our study results indicate that endophytic B. phytofirmans PsJN cells are active inside plants. Moreover, the activity of strain PsJN is affected by plant drought stress; it senses plant stress signals and adjusts its gene expression accordingly. IMPORTANCE: In recent years, plant growth-promoting endophytes have received steadily growing interest as an inexpensive alternative to resource-consuming agrochemicals in sustainable agriculture. Even though promising effects are recurrently observed under controlled conditions, these are rarely reproducible in the field or show undesirably strong variations. Obviously, a better understanding of endophyte activities in plants and the influence of plant physiology on these activities is needed to develop more-successful application strategies. So far, research has focused mainly on analyzing the plant response to bacterial inoculants. This prompted us to study the gene expression of the endophyte Burkholderia phytofirmans PsJN in potato plants. We found that endophytic PsJN cells express a wide array of genes and pathways, pointing to high metabolic activity inside plants. Moreover, the strain senses changes in the plant physiology due to plant stress and adjusts its gene expression pattern to cope with and adapt to the altered conditions. PMID- 26350964 TI - Growth-Phase-Specific Modulation of Cell Morphology and Gene Expression by an Archaeal Histone Protein. AB - In all three domains of life, organisms use nonspecific DNA-binding proteins to compact and organize the genome as well as to regulate transcription on a global scale. Histone is the primary eukaryotic nucleoprotein, and its evolutionary roots can be traced to the archaea. However, not all archaea use this protein as the primary DNA-packaging component, raising questions regarding the role of histones in archaeal chromatin function. Here, quantitative phenotyping, transcriptomic, and proteomic assays were performed on deletion and overexpression mutants of the sole histone protein of the hypersaline-adapted haloarchaeal model organism Halobacterium salinarum. This protein is highly conserved among all sequenced haloarchaeal species and maintains hallmark residues required for eukaryotic histone functions. Surprisingly, despite this conservation at the sequence level, unlike in other archaea or eukaryotes, H. salinarum histone is required to regulate cell shape but is not necessary for survival. Genome-wide expression changes in histone deletion strains were global, significant but subtle in terms of fold change, bidirectional, and growth phase dependent. Mass spectrometric proteomic identification of proteins from chromatin enrichments yielded levels of histone and putative nucleoid-associated proteins similar to those of transcription factors, consistent with an open and transcriptionally active genome. Taken together, these data suggest that histone in H. salinarum plays a minor role in DNA compaction but important roles in growth-phase-dependent gene expression and regulation of cell shape. Histone function in haloarchaea more closely resembles a regulator of gene expression than a chromatin-organizing protein like canonical eukaryotic histone. IMPORTANCE: Histones comprise the major protein component of eukaryotic chromatin and are required for both genome packaging and global regulation of expression. The current paradigm maintains that archaea whose genes encode histone also use these proteins to package DNA. In contrast, here we demonstrate that the sole histone encoded in the genome of the salt-adapted archaeon Halobacterium salinarum is both unessential and unlikely to be involved in DNA compaction despite conservation of residues important for eukaryotic histones. Rather, H. salinarum histone is required for global regulation of gene expression and cell shape. These data are consistent with the hypothesis that H. salinarum histone, strongly conserved across all other known salt-adapted archaea, serves a novel role in gene regulation and cell shape maintenance. Given that archaea possess the ancestral form of eukaryotic histone, this study has important implications for understanding the evolution of histone function. PMID- 26350965 TI - Novel Approaches Reveal that Toxoplasma gondii Bradyzoites within Tissue Cysts Are Dynamic and Replicating Entities In Vivo. AB - Despite their critical role in chronic toxoplasmosis, the biology of Toxoplasma gondii bradyzoites is poorly understood. In an attempt to address this gap, we optimized approaches to purify tissue cysts and analyzed the replicative potential of bradyzoites within these cysts. In order to quantify individual bradyzoites within tissue cysts, we have developed imaging software, BradyCount 1.0, that allows the rapid establishment of bradyzoite burdens within imaged optical sections of purified tissue cysts. While in general larger tissue cysts contain more bradyzoites, their relative "occupancy" was typically lower than that of smaller cysts, resulting in a lower packing density. The packing density permits a direct measure of how bradyzoites develop within cysts, allowing for comparisons across progression of the chronic phase. In order to capture bradyzoite endodyogeny, we exploited the differential intensity of TgIMC3, an inner membrane complex protein that intensely labels newly formed/forming daughters within bradyzoites and decays over time in the absence of further division. To our surprise, we were able to capture not only sporadic and asynchronous division but also synchronous replication of all bradyzoites within mature tissue cysts. Furthermore, the time-dependent decay of TgIMC3 intensity was exploited to gain insights into the temporal patterns of bradyzoite replication in vivo. Despite the fact that bradyzoites are considered replicatively dormant, we find evidence for cyclical, episodic bradyzoite growth within tissue cysts in vivo. These findings directly challenge the prevailing notion of bradyzoites as dormant nonreplicative entities in chronic toxoplasmosis and have implications on our understanding of this enigmatic and clinically important life cycle stage. IMPORTANCE: The protozoan Toxoplasma gondii establishes a lifelong chronic infection mediated by the bradyzoite form of the parasite within tissue cysts. Technical challenges have limited even the most basic studies on bradyzoites and the tissue cysts in vivo. Bradyzoites, which are viewed as dormant, poorly replicating or nonreplicating entities, were found to be surprisingly active, exhibiting not only the capacity for growth but also previously unrecognized patterns of replication that point to their being considerably more dynamic than previously imagined. These newly revealed properties force us to reexamine the most basic questions regarding bradyzoite biology and the progression of the chronic phase of toxoplasmosis. By developing new tools and approaches to study the chronic phase at the level of bradyzoites, we expose new avenues to tackle both drug development and a better understanding of events that may lead to reactivated symptomatic disease. PMID- 26350966 TI - A Noncanonical Autophagy Pathway Restricts Toxoplasma gondii Growth in a Strain Specific Manner in IFN-gamma-Activated Human Cells. AB - A core set of autophagy proteins is required for gamma interferon (IFN-gamma) mediated clearance of Toxoplasma gondii in the mouse because of their control of several downstream effectors, including immunity-related GTPases (IRGs) and guanylate-binding proteins (GBPs). However, these effectors are absent (i.e., IRGs) from or nonessential (i.e., GBPs) in IFN-gamma-activated human cells, raising the question of how these cells control parasite replication. Here, we define a novel role for ubiquitination and recruitment of autophagy adaptors in the strain-specific control of T. gondii replication in IFN-gamma-activated human cells. Vacuoles containing susceptible strains of T. gondii became ubiquitinated, recruited the adaptors p62 and NDP52, and were decorated with LC3. Parasites within LC3-positive vacuoles became enclosed in multiple layers of host membranes, resulting in stunting of parasite replication. However, LC3-positive T. gondii-containing vacuoles did not fuse with endosomes and lysosomes, indicating that this process is fundamentally different from xenophagy, a form of autophagy involved in the control of intracellular bacterial pathogens. Genetic knockout of ATG16L or ATG7 reverted the membrane encapsulation and restored parasite replication, indicating that core autophagy proteins involved in LC3 conjugation are important in the control of parasite growth. Despite a role for the core autophagy machinery in this process, upstream activation through Beclin 1 was not sufficient to enhance the ubiquitination of T. gondii-containing vacuoles, suggesting a lack of reliance on canonical autophagy. These findings demonstrate a new mechanism for IFN-gamma-dependent control of T. gondii in human cells that depends on ubiquitination and core autophagy proteins that mediate membrane engulfment and restricted growth. IMPORTANCE: Autophagy is a process of cellular remodeling that allows the cell to recycle senescent organelles and recapture nutrients. During innate immune responses in the mouse, autophagy is recruited to help target intracellular pathogens and thus eliminate them. However, the antimicrobial mediators that depend on autophagy in the mouse are not conserved in humans, raising the issue of how human cells control intracellular pathogens. Our study defines a new pathway for the control of the ubiquitous intracellular parasite T. gondii in human cells activated by IFN gamma. Recruitment of autophagy adaptors resulted in engulfment of the parasite in multiple membranes and growth impairment. Although susceptible type 2 and 3 stains of T. gondii were captured by this autophagy-dependent pathway, type 1 strains were able to avoid entrapment. PMID- 26350967 TI - The Complete Genome Sequence of Clostridium aceticum: a Missing Link between Rnf- and Cytochrome-Containing Autotrophic Acetogens. AB - Clostridium aceticum was the first isolated autotrophic acetogen, converting CO2 plus H2 or syngas to acetate. Its genome has now been completely sequenced and consists of a 4.2-Mbp chromosome and a small circular plasmid of 5.7 kbp. Sequence analysis revealed major differences from other autotrophic acetogens. C. aceticum contains an Rnf complex for energy conservation (via pumping protons or sodium ions). Such systems have also been found in C. ljungdahlii and Acetobacterium woodii. However, C. aceticum also contains a cytochrome, as does Moorella thermoacetica, which has been proposed to be involved in the generation of a proton gradient. Thus, C. aceticum seems to represent a link between Rnf- and cytochrome-containing autotrophic acetogens. In C. aceticum, however, the cytochrome is probably not involved in an electron transport chain that leads to proton translocation, as no genes for quinone biosynthesis are present in the genome. IMPORTANCE: Autotrophic acetogenic bacteria are receiving more and more industrial focus, as CO2 plus H2 as well as syngas are interesting new substrates for biotechnological processes. They are both cheap and abundant, and their use, if it results in sustainable products, also leads to reduction of greenhouse gases. Clostridium aceticum can use both gas mixtures, is phylogenetically not closely related to the commonly used species, and may thus become an even more attractive workhorse. In addition, its energy metabolism, which is characterized here, and the ability to synthesize cytochromes might offer new targets for improving the ATP yield by metabolic engineering and thus allow use of C. aceticum for production of compounds by pathways that currently present challenges for energy-limited acetogens. PMID- 26350968 TI - Field Science--the Nature and Utility of Scientific Fields. AB - Fields are the fundamental sociological units of science. Despite their importance, relatively little has been written about their emergence, composition, structure, and function in the scientific enterprise. This essay considers the nature of fields and their important role in maintaining information and providing normative standards for scientific work. We suggest that fields arise naturally as a consequence of increasing information and scientific specialization. New fields tend to emerge as research communities grow, which may reflect biologically determined optima for the size of human groups. The benefits of fields include the organization of scientists with similar interests into communities that collectively define the next important problems to pursue. In the discipline of microbiology, fields are often organized on the basis of phylogenetic differences between microorganisms being studied. Although fields are essential to the proper functioning of science, their emergence can restrict access by outsiders and sustain dogmas that hinder progress. We suggest mechanisms to improve the functioning of scientific fields and to promote interdisciplinary interaction between fields. PMID- 26350969 TI - Origin and Possible Genetic Recombination of the Middle East Respiratory Syndrome Coronavirus from the First Imported Case in China: Phylogenetics and Coalescence Analysis. AB - The Middle East respiratory syndrome coronavirus (MERS-CoV) causes a severe acute respiratory tract infection with a high fatality rate in humans. Coronaviruses are capable of infecting multiple species and can evolve rapidly through recombination events. Here, we report the complete genomic sequence analysis of a MERS-CoV strain imported to China from South Korea. The imported virus, provisionally named ChinaGD01, belongs to group 3 in clade B in the whole-genome phylogenetic tree and also has a similar tree topology structure in the open reading frame 1a and -b (ORF1ab) gene segment but clusters with group 5 of clade B in the tree constructed using the S gene. Genetic recombination analysis and lineage-specific single-nucleotide polymorphism (SNP) comparison suggest that the imported virus is a recombinant comprising group 3 and group 5 elements. The time resolved phylogenetic estimation indicates that the recombination event likely occurred in the second half of 2014. Genetic recombination events between group 3 and group 5 of clade B may have implications for the transmissibility of the virus. IMPORTANCE: The recent outbreak of MERS-CoV in South Korea has attracted global media attention due to the speed of spread and onward transmission. Here, we present the complete genome of the first imported MERS-CoV case in China and demonstrate genetic recombination events between group 3 and group 5 of clade B that may have implications for the transmissibility of MERS-CoV. PMID- 26350970 TI - Association with PAK2 Enables Functional Interactions of Lentiviral Nef Proteins with the Exocyst Complex. AB - Human immunodeficiency virus type 1 (HIV-1) Nef enhances virus replication and contributes to immune evasion in vivo, but the underlying molecular mechanisms remain incompletely defined. Nef interferes with host cell actin dynamics to restrict T lymphocyte responses to chemokine stimulation and T cell receptor engagement. This relies on the assembly of a labile multiprotein complex including the host kinase PAK2 that Nef usurps to phosphorylate and inactivate the actin-severing factor cofilin. Components of the exocyst complex (EXOC), an octameric protein complex involved in vesicular transport and actin remodeling, were recently reported to interact with Nef via the same molecular surface that mediates PAK2 association. Exploring the functional relevance of EXOC in Nef-PAK2 complex assembly/function, we found Nef-EXOC interactions to be specifically mediated by the PAK2 interface of Nef, to occur in infected human T lymphocytes, and to be conserved among lentiviral Nef proteins. In turn, EXOC was dispensable for direct downstream effector functions of Nef-associated PAK2. Surprisingly, PAK2 was essential for Nef-EXOC association, which required a functional Rac1/Cdc42 binding site but not the catalytic activity of PAK2. EXOC was dispensable for Nef functions in vesicular transport but critical for inhibition of actin remodeling and proximal signaling upon T cell receptor engagement. Thus, Nef exploits PAK2 in a stepwise mechanism in which its kinase activity cooperates with an adaptor function for EXOC to inhibit host cell actin dynamics. IMPORTANCE: Human immunodeficiency virus type 1 (HIV-1) Nef contributes to AIDS pathogenesis, but the underlying molecular mechanisms remain incompletely understood. An important aspect of Nef function is to facilitate virus replication by disrupting T lymphocyte actin dynamics in response to stimulation via its association with the host cell kinase PAK2. We report here that the molecular surface of Nef for PAK2 association also mediates interaction of Nef with EXOC and establish that PAK2 provides an essential adaptor function for the subsequent formation of Nef-EXOC complexes. PAK2 and EXOC specifically cooperate in the inhibition of actin dynamics and proximal signaling induced by T cell receptor engagement by Nef. These results establish EXOC as a functionally relevant Nef interaction partner, emphasize the suitability of the PAK2 interaction surface for future therapeutic interference with Nef function, and show that such strategies need to target activity-independent PAK2 functions. PMID- 26350971 TI - Modeling the Context-Dependent Associations between the Gut Microbiome, Its Environment, and Host Health. AB - Changes in the gut microbiome are often associated with disease. One of the major goals in microbiome research is determining which components of this complex system are responsible for the observed differences in health state. Most studies apply a reductionist approach, wherein individual organisms are evaluated independently of the surrounding context of the microbiome. While such methods have yielded valuable insights into the microbiome, they fail to identify patterns that may be obscured by contextual variation. A recent report by Schubert et al. [A. M. Schubert, H. Sinani, and P. D. Schloss, mBio 6(4):e00974 15, 2015, doi: 10.1128/mBio.00974-15] communicates an alternative approach to the study of the microbiome's association with host health. By coupling a multifactored experimental design with regression modeling, the authors are able to profile context-dependent changes in the microbiome and predict health status. This work underscores the value of incorporating model-based procedures into the investigation of the microbiome and illustrates the potential clinical transformations that may arise through their use. PMID- 26350973 TI - Middle East Respiratory Syndrome Coronavirus Recombination and the Evolution of Science and Public Health in China. PMID- 26350972 TI - N-Acetylglucosamine-Induced Cell Death in Candida albicans and Its Implications for Adaptive Mechanisms of Nutrient Sensing in Yeasts. AB - Single-celled organisms have different strategies to sense and utilize nutrients in their ever-changing environments. The opportunistic fungal pathogen Candida albicans is a common member of the human microbiota, especially that of the gastrointestinal (GI) tract. An important question concerns how C. albicans gained a competitive advantage over other microbes to become a successful commensal and opportunistic pathogen. Here, we report that C. albicans uses N acetylglucosamine (GlcNAc), an abundant carbon source present in the GI tract, as a signal for nutrient availability. When placed in water, C. albicans cells normally enter the G0 phase and remain viable for weeks. However, they quickly lose viability when cultured in water containing only GlcNAc. We term this phenomenon GlcNAc-induced cell death (GICD). GlcNAc triggers the upregulation of ribosomal biogenesis genes, alterations of mitochondrial metabolism, and the accumulation of reactive oxygen species (ROS), followed by rapid cell death via both apoptotic and necrotic mechanisms. Multiple pathways, including the conserved cyclic AMP (cAMP) signaling and GlcNAc catabolic pathways, are involved in GICD. GlcNAc acts as a signaling molecule to regulate multiple cellular programs in a coordinated manner and therefore maximizes the efficiency of nutrient use. This adaptive behavior allows C. albicans' more efficient colonization of the gut. IMPORTANCE: The ability to rapidly and appropriately respond to nutrients in the environment is crucial to free-living microorganisms. To maximize the use of available nutrients, microorganisms often use a limiting nutritional component as a signal to coordinate multiple biological processes. The human fungal pathogen Candida albicans uses N-acetylglucosamine (GlcNAc) as a signal for the availability of external nutrient resources. GlcNAc induces rapid cell death in C. albicans due to the constitutive activation of oxidative metabolism and accumulation of reactive oxygen species (ROS), and multiple pathways are involved in its regulation. This study sheds light on the mechanisms of niche specialization of pathogenic fungi and raises the possibility that this cell death pathway could be an unexplored therapeutic target. PMID- 26350974 TI - Structural Characterization and Evaluation of the Antioxidant Activity of Phenolic Compounds from Astragalus taipaishanensis and Their Structure-Activity Relationship. AB - Eight phenolic compounds were isolated using bio-guided isolation and purified from the roots of Astragalus taipaishanensis Y. C. Ho et S. B. Ho (A. taipaishanensis) for the first time. Their structures were elucidated by ESI-MS, HR-ESI-MS, 1D-NMR and 2D-NMR as 7,2'-dihydroxy-3',4'-dimethoxy isoflavan (1), formononetin (2), isoliquiritigenin (3), quercetin (4), kaempferol (5), ononin (6), p-hydroxybenzoic acid (7) and vanillic acid (8). Six flavonoids (compounds 1 6) exhibited stronger antioxidant activities (determined by DPPH, ABTS, FRAP and lipid peroxidation inhibition assays) than those of BHA and TBHQ and also demonstrated noticeable protective effects (particularly quercetin and kaempferol) on Escherichia coli under oxidative stress. Additionally, the chemical constituents compared with those of Astragalus membranaceus and the structure-activity relationship of the isolated compounds were both analyzed. The results clearly demonstrated that A. taipaishanensis has the potential to be selected as an alternative medicinal and food plant that can be utilized in health food products, functional tea and pharmaceutical products. PMID- 26350975 TI - Short- and mid-term results after transapical transcatheter aortic valve replacement in nonagenarians. AB - BACKGROUND: Recent reports have suggested that advanced age may preclude favorable outcomes in transcatheter aortic valve replacement (TAVR), particularly when performed via transapical (TA) access. However, detailed examinations of TA TAVR in nonagenarian patients are lacking in the contemporary literature. We therefore describe our experience with 25 consecutive nonagenarians who underwent TA-TAVR and report their short- and mid-term outcomes. METHODS: We identified all patients 90 years old or greater who underwent TA-TAVR between 2009-2014 at our institution. Demographic, comorbidity and echocardiographic data were obtained for all patients as were their in-hospital, 30-day, and 1-year outcomes. Overall survival was calculated using the Kaplan-Meier method. RESULTS: The mean Society of Thoracic Surgeons' predicted risk of mortality was 10.2% (SD+/-3.4). Twenty four nonagenarians received TA-TAVR secondary to severe aortic stenosis while 1 had a valve-in-valve procedure for a regurgitant bioprosthetic valve. There were no conversions to open surgery, no aborted procedures, and no in-hospital deaths or strokes; 44% of patients (N.=11) were discharged to home. Five patients required cardiac rehospitalization within the first 30 days and 2 experienced strokes during the first year. Overall 30-day and 1-year survival were 100% and 83%, respectively. CONCLUSIONS: TA-TAVR can safely be performed on nonagenarians subjected to otherwise standard selection criteria. Chronology should not stand as a routine contraindication to this procedure; rather, comorbidities and functional status should define patient eligibility for TA-TAVR. PMID- 26350976 TI - The risk for type B aortic dissection in Marfan syndrome. AB - Marfan syndrome is the most prevalent connective tissue disorder, with an autosomal dominant inheritance with variable penetrance. This paper aims to summarize epidemiology and treatment for type B dissection in Marfan patients. PMID- 26350977 TI - Contribution and distribution of inorganic ions and organic compounds to the osmotic adjustment in Halostachys caspica response to salt stress. AB - The mechanism by which plants cope with salt stress remains poorly understood. The goal of this study is to systematically investigate the contribution and distribution of inorganic ions and organic compounds to the osmotic adjustment (OA) in the halophyte species Halostachys caspica. The results indicate that 100 200 mM NaCl is optimal for plant growth; the water content and degree of succulence of the assimilating branches are higher in this treatment range than that in other treatments; parenchyma cells are more numerous with 100 mM NaCl treatment than they are in control. Inorganic ions (mainly Na+ and Cl-) may play a more important role than organic compounds in NaCl-induced OA and are the primary contributors in OA in H. caspica. The inorganic ions and organic solutes display a tissue-dependent distribution. Na+ and Cl- are accumulated in the reproductive organs and within assimilating branches, which may represent a mechanism for protecting plant growth by way of salt ion dilution and organ abscission. Additionally, OA via increased accumulation of organic substances also protected plant growth and development. This finding provides additional evidence for plant tolerance to salinity stress which can be used for breeding new cultivars for stress tolerance. PMID- 26350978 TI - Complete genome sequence of a tentative new caulimovirus from the medicinal plant Atractylodes macrocephala. AB - A total of nine contigs related to caulimovirus-like sequences were detected using high-throughput paired-end RNA sequencing. An attempt to find the plant sample infected with this type of virus identified the medicinal plant Atractylodes macrocephala Koidzumi showing mild mottle symptoms. Subsequently, the complete DNA genome sequence of the Atractylodes virus was determined. The 8,105-nt genome of the virus was composed of six open reading frames and displayed the highest nucleotide sequence identity (70%) with soybean Putnam virus. Based upon the symptoms observed on the source plant, we propose to refer to this new member of the genus Caulimovirus as atractylodes mild mottle virus. PMID- 26350979 TI - Comparative molecular genetic analysis of simian and human HIV-1 integrase interactor INI1/SMARCB1/SNF5. AB - Human integrase interactor 1 (INI1/SMARCB1/SNF5) is a chromatin-remodeling molecule that binds to HIV-1 integrase and enhances proviral DNA integration. INI1 is also known as a tumor suppressor gene and has been found to be mutated in several aggressive tumors such as rhabdoid and lymphoid tumors. To study the function of simian INI1, we screened and cloned simian INI1 cDNA from B lymphoma cells of rhesus monkeys using RT-PCR. Sequence analysis showed 23 single nucleotide differences compared to the human ortholog, which, however, did not result in amino acid changes, and the amino acid sequence is therefore 100% conserved between human and simian INI1. Two alternatively spliced isoforms, INI1a and INI1b, were also found in simian INI1. These two isoforms did not show any functional difference in HIV-1 proviral DNA integration and nuclear localization, suggesting that the specificity of simian INI1 would not be a factor preventing HIV-1 infection of a simian host. Nevertheless, INI1b is expressed only in established cancer cell lines such as Jurkat and COS-7 cells, and not in primary cells, suggesting that INIlb could be an indicator of cell transformation. PMID- 26350980 TI - Genetic and biological characterization of Muko virus, a new distinct member of the species Great Island virus (genus Orbivirus, family Reoviridae), isolated from ixodid ticks in Japan. AB - Among the tick-borne orbiviruses (genus Orbivirus, family Reoviridae), 36 serotypes are currently classified within a single virus species, Great Island virus. In this study, we report the first characterization of a tick-borne orbivirus isolated from the tick Ixodes turdus in Japan, which we identified as a new member of the species Great Island virus. The virus isolate, designated Muko virus (MUV), replicated and induced cytopathic effects in BHK-21, Vero E6, and CCL-141 cells and caused high mortality in suckling mice after intracerebral inoculation. Full genome sequence analysis showed that MUV shared the greatest phylogenetic similarity with Tribec virus in terms of the amino acid sequences of all viral proteins except for outer capsid protein 1 (OC1; VP4 of MUV). Analysis of genome segment 9 in MUV detected an uninterrupted open reading frame that overlaps with VP6 (Hel), which putatively encodes a molecular and functional equivalent of NS4 from Great Island virus. Our study provides new insights into the geographic distribution, genetic diversity, and evolutionary history of the members of the species Great Island virus. PMID- 26350981 TI - Ambient air pollution and emergency department visits for asthma: a multi-city assessment of effect modification by age. AB - Previous studies have found strong associations between asthma morbidity and major ambient air pollutants. Relatively little research has been conducted to assess whether age is a factor conferring susceptibility to air pollution-related asthma morbidity. We investigated the short-term relationships between asthma emergency department (ED) visits and ambient ozone (O3), carbon monoxide (CO), nitrogen dioxide (NO2), sulfur dioxide (SO2), and fine particulate matter (PM2.5) in Atlanta (1993-2009), Dallas (2006-2009), and St. Louis (2001-2007). City specific daily time-series analyses were conducted to estimate associations by age group (0-4, 5-18, 19-39, 40-64, and 65+ years). Sub-analyses were performed stratified by race and sex. City-specific rate ratios (RRs) were combined by inverse-variance weighting to provide an overall association for each strata. The overall RRs differed across age groups, with associations for all pollutants consistently strongest for children aged 5-18 years. The patterns of association across age groups remained generally consistent when models were stratified by sex and race, although the strong observed associations among 5-18 year olds appeared to be partially driven by non-white and male patients. Our findings suggest that age is a susceptibility factor for asthma exacerbations in response to air pollution, with school-age children having the highest susceptibility. PMID- 26350982 TI - Intermittency ratio: A metric reflecting short-term temporal variations of transportation noise exposure. AB - Most environmental epidemiology studies model health effects of noise by regressing on acoustic exposure metrics that are based on the concept of average energetic dose over longer time periods (i.e. the Leq and related measures). Regarding noise effects on health and wellbeing, average measures often cannot satisfactorily predict annoyance and somatic health effects of noise, particularly sleep disturbances. It has been hypothesized that effects of noise can be better explained when also considering the variation of the level over time and the frequency distribution of event-related acoustic measures, such as for example, the maximum sound pressure level. However, it is unclear how this is best parametrized in a metric that is not correlated with the Leq, but takes into account the frequency distribution of events and their emergence from background. In this paper, a calculation method is presented that produces a metric which reflects the intermittency of road, rail and aircraft noise exposure situations. The metric termed intermittency ratio (IR) expresses the proportion of the acoustical energy contribution in the total energetic dose that is created by individual noise events above a certain threshold. To calculate the metric, it is shown how to estimate the distribution of maximum pass-by levels from information on geometry (distance and angle), traffic flow (number and speed) and single event pass-by levels per vehicle category. On the basis of noise maps that simultaneously visualize Leq, as well as IR, the differences of both metrics are discussed. PMID- 26350984 TI - Mobile phones for retinopathy of prematurity screening in Lagos, Nigeria, sub Saharan Africa. AB - PURPOSE: Retinopathy of prematurity (ROP), thought to be rare in Nigeria, sub Saharan Africa, has been reported in recent studies. Developing cost-effective screening is crucial for detecting retinal changes amenable to treatment. This study describes the use of an iPhone combined with a 20-D lens in screening for ROP in Lagos, Nigeria. METHODS: The ROP screening program was approved by the Lagos University Teaching Hospital Ethical Committee. Preterm infants with birthweight of less than 1.5 kg or gestational age of less than 32 weeks were screened. In conjunction with the neonatologist, topical tropicamide (0.5%) and phenylephrine (2.5%) was used to dilate the pupils. A pediatric lid speculum was used. Indirect ophthalmoscopy was used to examine the fundus to ensure there were no missed diagnoses. An iPhone 5 with 20-D lens was used to examine the fundus. The App Filmic Pro was launched in the video mode. The camera flash served as the source of illumination. Its intensity was controlled by the app. The 20-D lens was used to capture the image of the retina, which was picked up by the camera system of the mobile phone. Another app, Aviary, was used to edit the picture. RESULTS: The images captured by the system were satisfactory for staging and determining the need for treatment. CONCLUSIONS: An iPhone combined with a 20-D lens appear to be useful in screening for ROP in resource-poor settings. More studies are needed in this area. PMID- 26350983 TI - Bisphenol A exposure pathways in early childhood: Reviewing the need for improved risk assessment models. AB - Bisphenol A (BPA) is a plasticiser found in a number of household plastics, electronics, and food-packaging materials. Over the past 5 years, several human epidemiological studies have reported a positive association between BPA exposure and adverse health outcomes in children, including obesity, asthma, preterm birth, and neuro-behavioural disturbances. These findings are in conflict with international environmental risk assessment models, which predict daily exposure levels to BPA should not pose a risk to child health. The aim of this review is to provide an overview of the evidence for different exposure sources and potential exposure pathways of BPA in early childhood. By collating the findings from experimental models and exposure associations observed in human bio monitoring studies, we affirm the potential for non-dietary sources to make a substantial contribution to total daily exposure in young children. Infants and toddlers have distinctive exposure sources, physiology, and metabolism of endocrine-disrupting chemicals. We recommend risk-assessment models implement new frameworks, which specifically address exposure and hazard in early childhood. This is particularly important for BPA, which is present in numerous products in the home and day-care environments, and for which animal studies report contradictory findings on its safety at environmentally relevant levels of exposure. PMID- 26350985 TI - Choroidal thickness in systemic arterial hypertension. AB - PURPOSE: To assess choroidal thickness changes in young adults with systemic arterial hypertension. METHODS: This prospective study comprised 80 hypertensive patients and 80 healthy control subjects. Choroidal thickness was measured with spectral-domain optical coherence tomography (SD-OCT) (RS-3000, Nidek). Choroidal thickness was obtained at the subfovea, 500 um, 1000 um, and 1500 um nasal to the fovea (N500, N1000, N1500) and 500 um, 1000 um, and 1500 um temporal to the fovea (T500, T1000, T1500). Systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) were measured with a mercury sphygmomanometer. Only the right eye values were used for statistical comparisons between the groups. RESULTS: Mean age was 23.8 +/- 2.8 years in hypertensive subjects and 23.5 +/- 2.1 years in the control group (p = 0.945). All choroidal thickness measurements (mean choroidal thickness, subfoveal choroidal thickness, all nasal and all temporal choroidal thicknesses) were significantly lower in hypertensive subjects (p<0.001 for subfoveal, N500, T500, T1000, T1500; p = 0.001 for N1000; and p = 0.012 for N1500). The correlations between choroidal thickness measurements and blood pressure (SBP, DBP, MAP) were insignificant (p>0.05 for all correlations). Choroidal thickness measurements were also insignificantly correlated with disease duration (p>0.05 for all correlations). CONCLUSIONS: The results of this study demonstrated that choroidal thickness decreases in patients with systemic arterial hypertension. This may be caused by arteriolar sclerosis and vascular contraction caused by high intravascular pressure in the choroid. PMID- 26350986 TI - Effect of intracameral triamcinolone acetonide on postoperative intraocular inflammation in pediatric traumatic cataract. AB - PURPOSE: To study the effect of a single intracameral injection of triamcinolone acetonide at the end of pediatric traumatic cataract surgery on postoperative inflammation. METHODS: This prospective interventional study comprised 40 eyes of children with unilateral traumatic cataract. Patients were classified into 2 groups: the study group, in which intraoperative intracameral triamcinolone acetonide (2 mg) was used at the end of surgery; and a control group, which did not receive intracameral triamcinolone acetonide. RESULTS: The study group included 20 eyes of patients with an average age of 6 +/- 2.8 years. The control group included 20 eyes of patients with an average age of 6 +/- 2.1 years. No serious intraoperative complications occurred. In the immediate postoperative period, 3 eyes of the control group (15.0%) developed a fibrinous anterior chamber reaction. None of the study group eyes developed a similar reaction. There were no cases of endophthalmitis. In addition, 3 eyes (15%) in the control group had obscuration of the visual axis at the last follow-up. This complication was not encountered in the study group. Posterior synechiae and cellular deposits were observed in 4 eyes (20%) in the study group and 8 eyes (40%) in the control group at 1 month and at the last follow-up. CONCLUSIONS: The use of intracameral triamcinolone decreased anterior segment inflammation postoperatively in children who had surgery for traumatic cataract. PMID- 26350987 TI - Clinical experience with the WIOL-CF accommodative bioanalogic intraocular lens: Czech national observational registry. AB - PURPOSE: To assess efficacy and patient satisfaction after cataract surgery and implantation of a new accommodative bioanalogic intraocular lens (IOL). METHODS: We evaluated the collected data of 48 patients with bilateral cataract surgery and Wichterle IOL (WIOL) implantation included in the Czech national observational registry. Monocular and binocular uncorrected distance visual acuity (UDVA), uncorrected intermediate visual acuity, uncorrected near visual acuity (UNVA), best spectacle-corrected visual acuity for distance (CDVA), best spectacle-corrected visual acuity for near (CNVA), distance-corrected near visual acuity (DCNVA), and distance-corrected intermediate visual acuity were evaluated 6 months after surgery. Subjective patient satisfaction was assessed at 3 months postoperatively. RESULTS: The mean monocular UDVA was 0.074 +/- 0.108 logMAR, the mean monocular CDVA was 0.047 +/- 0.125 logMAR, the mean monocular UNVA was 0.328 +/- 0.146 logMAR, the mean monocular DCNVA was 0.339 +/- 0.131 logMAR, and the mean monocular CNVA was 0.139 +/- 0.107 logMAR. A total of 24 patients (50%) had no problems with any light phenomena. A total of 18 patients were very satisfied (37.5%), 11 were satisfied (22.9%), 15 (31.2%) were rather satisfied, 4 (8.3%) were rather dissatisfied, and 0 were dissatisfied. CONCLUSIONS: The WIOL continuous focus polyfocal lens offers very good vision at far and intermediate distance comparable with other types of multifocal IOLs, and relatively good near vision, while the incidence of adverse side phenomena is relatively low. PMID- 26350988 TI - Bilateral type III Duane syndrome: a case report. AB - PURPOSE: Duane syndrome (DS) belongs to a group of congenital retraction syndromes, the incidence of which varies between 2% and 4% in patients with strabismus. In most cases the damage is unilateral, but it manifests as bilateral in about 20% of cases. According to the classification of Huber, type III DS exhibits a limitation of abduction and adduction. METHODS: We report the case of a 5-year-old boy from Eastern Europe who was taken to the hospital because he was unable to move both eyes horizontally from birth and had not been previously seen by an ophthalmologist. RESULTS: The examination showed inability to abduct and adduct bilaterally, with narrowing of the palpebral fissures on attempted adduction. The patient was diagnosed with bilateral type III DS. CONCLUSIONS: Treatment is individualized on a case-by-case basis. For our patient, monitoring by way of regular checkups was chosen, with the parents rejecting surgery for now. PMID- 26350989 TI - Improved outcome after primary vitrectomy in diabetic patients treated with statins. AB - PURPOSE: To evaluate the effect of preoperative statin treatment on the outcome of primary vitrectomy in type 1 and 2 diabetic patients. METHODS: In this open, observational institutional study, a total of 192 eyes of 171 type 1 and 2 adult diabetic patients admitted for primary vitrectomy for management of sight threatening forms of diabetic retinopathy were divided according to the use of lipid-lowering therapy: those with statin treatment (79 eyes of 73 patients) and those taking no statin medication (113 eyes of 98 patients). One-month best corrected visual acuity (BCVA) gain and cumulative 12-month revitrectomy frequency were analyzed. RESULTS: In multivariate linear regression, diabetic patients with statin treatment had a better 1-month BCVA improvement than did those without statin treatment (absolute difference 0.26, 95% confidence interval [CI] 0.02-0.50, p = 0.028). Subgroup analysis revealed that diabetic patients on statin had better postoperative BCVA improvement when preoperative status included partial or panretinal laser photocoagulation (p = 0.042 and p = 0.049) and anti-vascular endothelial growth factor therapy (p = 0.011). Moreover, diabetic patients with preoperative macular edema (p = 0.009), vitreous hemorrhage (p<0.001), proliferative retinopathy (p<0.001), or tractional retinal detachment (p = 0.010) had better BCVA recovery if receiving statin. In Cox proportional hazards regression model, revitrectomies in our 12-month follow-up were less frequent in diabetic patients on statin treatment (hazard ratio 0.28, 95% CI 0.08-0.93, p = 0.037). CONCLUSIONS: These data provide novel insight into the potential clinical benefit for patients with sight-threatening diabetic retinopathy undergoing vitrectomy treated with statin. PMID- 26350990 TI - A case of severe corneal flattening after Descemet stripping endothelial keratoplasty. AB - PURPOSE: To report a case of extreme corneal flattening after initially uneventful Descemet stripping endothelial keratoplasty (DSEK). METHODS: A 76-year old man underwent uneventful DSEK for pseudophakic bullous keratopathy (PBK) in his left eye. Postoperative evaluations were performed using anterior segment optical coherence tomography and biomicroscopy. RESULTS: The DSEK graft showed full adherence to the host stroma. Two weeks after surgery, the transplanted cornea developed pronounced flattening of the central corneal curvature accompanied by graft folds and remained unchanged until the most recent follow-up 20 weeks after surgery. CONCLUSIONS: Severe corneal flattening may be an undescribed complication occurring after uneventful DSEK, without any concomitant ocular pathology or detectable cause. PMID- 26350991 TI - Lamotrigine-induced tubulointerstitial nephritis and uveitis-atypical Cogan syndrome. AB - PURPOSE: To report a case of lamotrigine-induced tubulointerstitial nephritis and uveitis (TINU)-atypical Cogan syndrome. METHODS: Case report. RESULTS: A 16-year old boy with traumatic brain injury and seizures presented to the emergency department with facial swelling, rash, and back pain several days after increasing lamotrigine dose secondary to a breakthrough seizure. Creatinine, urine beta2 microglobulin, and eosinophils were elevated. Antinuclear antibodies, antineutrophil cytoplasmic antibodies, angiotensin-converting enzyme, and complement were normal. Renal biopsy showed acute granulomatous tubulointerstitial nephritis. Lamotrigine was discontinued, intravenous steroids were initiated, and the patient was discharged on Ativan and prednisone. Subsequently, he was diagnosed with bilateral anterior uveitis (vision 20/30 bilaterally) and started on prednisolone and cyclopentolate. Two months later, he developed a branch retinal artery occlusion in the right eye (vision 20/70) and bilateral ocular hypertension for which timolol-brimonidine and dorzolamide were added. Neuroimaging and hypercoagulability workup was unremarkable. Vision and intraocular pressure improved, while uveitis remained recalcitrant. Several months later, the patient developed central serous retinopathy in the right eye (vision 20/30). Prednisone was stopped but restarted due to methotrexate intolerance. A month later, he reported dizziness and was diagnosed with severe bilateral sensorineural hearing loss. Brain magnetic resonance imaging showed foci of perivascular, subcortical, and cochlear enhancement. Transtympanic Decadron injections and infliximab infusions were initiated. At the final visit, vision remained at 20/30 with trace anterior chamber reaction bilaterally while on timolol-brimonidine, dorzolamide, and prednisolone. CONCLUSIONS: An idiosyncratic drug reaction should be considered in the differential diagnosis of TINU-atypical Cogan syndrome. PMID- 26350992 TI - Grooved and nongrooved clear corneal incisions in phacoemulsification: permeability study. AB - PURPOSE: To detect the inflow of trypan blue through grooved and nongrooved sutureless self-sealing clear corneal incisions at the end of phacoemulsification as compared to a control group. METHODS: A prospective randomized masked trial considered 52 eyes randomized into 3 groups in which phacoemulsification was performed: group A, nongrooved incisions; group B, grooved incisions; and group C, controls. By the end of each surgery, trypan blue was instilled on the ocular surface in groups A and B and rinsed out after 2 minutes. A sample of the anterior chamber content was collected and analyzed by high-performance liquid chromatography to identify and quantify the trypan blue concentration. The presence of trypan blue was expressed as a specific single peak graphic image. The mean areas of these peaks were used to assess the groups using a nonparametric Mann-Whitney test. RESULTS: There was a statistically significant difference between the nongrooved incisions group and the control group (p = 0.0448). No significant difference was observed between group B (grooved incision) and controls (p = 0.1800). CONCLUSIONS: Trypan blue was detected in the anterior chamber when nongrooved clear corneal incision was used. There was no trypan blue detection in the group with grooved clear corneal main incisions. PMID- 26350993 TI - Smartphone-based fundus camera device (MII Ret Cam) and technique with ability to image peripheral retina. AB - PURPOSE: To demonstrate an inexpensive smartphone-based fundus camera device (MII Ret Cam) and technique with ability to capture peripheral retinal pictures. METHODS: A fundus camera was designed in the form of a device that has slots to fit a smartphone (built-in camera and flash) and 20-D lens. With the help of the device and an innovative imaging technique, high-quality fundus videos were taken with easy extraction of images. RESULTS: The MII Ret Cam and innovative imaging technique was able to capture high-quality images of peripheral retina such as ora serrata and pars plana apart from central fundus pictures. CONCLUSIONS: Our smartphone-based fundus camera can help clinicians to monitor diseases affecting both central and peripheral retina. It can help patients understand their disease and clinicians convincing their patients regarding need of treatment especially in cases of peripheral lesions. Imaging peripheral retina has not been demonstrated in existing smartphone-based fundus imaging techniques. The device can also be an inexpensive tool for mass screening. PMID- 26350995 TI - Combined use of Doppler OCT and en face OCT functions for discrimination of an aneurysm in the lamina cribrosa from a disc hemorrhage. AB - PURPOSE: In addition to retinal nerve fiber layer thickness measurements, the recently introduced AngioVue optical coherence tomography (OCT) offers corresponding layer-by-layer Doppler OCT and en face OCT functions, for simultaneous evaluation of perfusion and structure of the optic nerve head. We investigated the clinical usefulness of combined use of Doppler and en face Fourier-domain OCT functions of the AngioVue Fourier-domain OCT for discrimination of a disc hemorrhage and a disc hemorrhage-like atypical vessel structure located deep in the lamina cribrosa. CASE REPORT: We present our findings with AngioVue OCT on a disc hemorrhage and a spatially related retinal nerve fiber layer bundle defect in a glaucomatous eye (case 1). Both alterations were detected on en face OCT images without any Doppler OCT signal. We also report on an aneurysm suggestive for a disc hemorrhage on clinical examination and disc photography in a treated ocular hypertensive eye (case 2). The aneurysm was within the lamina cribrosa tissue at the border of the cup and the neuroretinal rim. This vascular structure produced strong Doppler signals but no structurally detectable signs on the en face OCT images. CONCLUSIONS: Combined evaluation of corresponding Doppler OCT and en face OCT images enables ophthalmologists to easily separate true disc hemorrhages from disc hemorrhage like deep vascular structures. This is of clinical significance in preventing unnecessary intensification of pressure-lowering treatment in glaucoma. PMID- 26350994 TI - A therapeutic trial of valganciclovir in patients with uveitis and positive Epstein-Barr virus early antigen D IgG titers. AB - PURPOSE: To evaluate the effectiveness of a therapeutic trial of valganciclovir in patients with uveitis with positive Epstein-Barr virus early antigen D immunoglobulin G titers (EBV EA-D). METHODS: We performed a retrospective chart review of 14 patients at the Massachusetts Eye Research and Surgery Institution who had uveitis with positive EBV EA-D but negative studies for all other causes of uveitis and were treated with valganciclovir 450 mg twice a day or valganciclovir 900 mg twice a day between January 2010 and August 2014. RESULTS: Nine of 14 patients, who had presumed EBV reactivation with associated intraocular inflammation, were successfully treated with valganciclovir: 3 of these were treated with valganciclovir 450 mg twice a day and 6 were treated with valganciclovir 900 mg twice a day. Five of 14 patients failed to respond to valganciclovir with persistent inflammation after at least 2 weeks of valganciclovir therapy, and were subsequently treated with immunomodulatory therapy to control inflammation. CONCLUSIONS: Uveitis can be caused by EBV infection/reactivation. A therapeutic trial with valganciclovir 450 mg twice a day for 1 month in patients with uveitis with positive EBV EA antibody may be beneficial. PMID- 26350996 TI - Cataract surgery in patients with nanophthalmos: results and complications. AB - PURPOSE: To evaluate phacoemulsification surgery results and complications in patients with nanophthalmos. METHODS: The records of 9 patients with nanophthalmos who had cataract surgery from January 2011 through January 2015 were retrospectively reviewed. Nanophthalmos was diagnosed by the presence of an eye with an axial length (AL) less than 20.5 mm. The records were reviewed for ocular diagnosis, keratometry, anterior chamber depth (ACD), AL, ocular surgeries, visual acuity, and complications. RESULTS: A total of 14 eyes of 9 patients (8 women, 1 man) with a mean age of 72 years (range 48-86) were reviewed. Mean AL was 18.72 mm and mean ACD was 2.30 mm. Mean preoperative spherical equivalent (+8.55 +/- 6.44 diopters (D)) was reduced to +0.30 +/- 2.17 D at last follow-up visit. Mean best-corrected visual acuity (BCVA) was +0.68 +/- 0.55 logarithm of the minimum angle of resolution (logMAR) preoperatively and improved to +0.55 +/- 0.73 logMAR at last follow-up visit. Visual acuity remained stable or improved in 11 eyes. Five eyes did not achieve final BCVA >=+0.3 logMAR. Complications occurred in 3 eyes (21.4%) and included 1 case of posterior capsule rupture, 1 case of severe iritis and rhegmatogenous retinal detachment 2 weeks postoperatively, and 1 other case of iritis. No postoperative uveal effusion was seen. CONCLUSIONS: Although phacoemulsification seems to be relatively safe in nanophthalmic eyes, surgeons need to be aware of the challenges of this procedure in these high-risk eyes. Nevertheless, with careful preoperative evaluation and planning, most cases were uncomplicated and resulted in improvement of BCVA. PMID- 26350997 TI - Prevalence of reticular pseudodrusen in eyes with newly presenting neovascular age-related macular degeneration. AB - PURPOSE: To use multimodal imaging to evaluate the prevalence of reticular pseudodrusen (RPD) in eyes with newly presenting neovascular age-related macular degeneration (nAMD) in a UK population and explore associations with RPD and angiographic subtypes of nAMD. METHODS: A retrospective review of all spectral domain optical coherence tomography, color fundus photographs, red-free and blue channel images, and fundus fluorescein angiograms of 202 consecutive patients who presented to a rapid access macular clinic over a 4-year period was performed. All images were graded by at least 2 ophthalmologists for the presence of RPD and choroidal neovascular membrane (CNV) subtypes. RESULTS: A total of 231 consecutive eyes were studied, of which 131 (56.7%) were in women. Of these, 51 eyes with CNV (22.1%) had identifiable RPD, with one or more imaging methods in that eye. A total of 30.3% of patients with newly presenting CNV in either or both eyes had identifiable RPD. The RPD were bilateral in 85.4% of patients and were identified more commonly in women than men (72.5% vs 27.5%), a difference that reached statistical significance (p = 0.011). No association between RPD and any particular CNV subtype was demonstrated, including for retinal angiomatous proliferations (RAP). CONCLUSIONS: Reticular pseudodrusen have a high prevalence in eyes presenting with nAMD (22.1%), although at rates much lower than that of conventional drusen. They are largely a bilateral finding, occurring more frequently in women. Unlike other previous reports, we found no difference in their occurrence between the different subtypes of CNV including RAPs. PMID- 26350999 TI - The roles of different salts and a novel osmotic pressure control strategy for improvement of DHA production by Schizochytrium sp. AB - The effects of different osmotic pressure, changed by six salts (NaCl, Na2SO4, (NH4)2SO4, KH2PO4 and MSG), on cell growth and DHA synthesis by Schizochytrium sp. were investigated. Six optimal mediums were obtained to study different osmotic pressure combinations at cell growth stage and DHA synthesis stage. Results showed that cultivated cell in higher osmotic pressure condition and fermented in lower osmotic pressure condition was benefit to enhance DHA synthesis. Combination 17-6 could get the maximum cell dry weight of 56.95 g/L and the highest DHA percentage in total fatty acids of 55.21%, while combination 17-B could get the highest lipid yield of 33.47 g/L with 42.10% DHA in total fatty acids. This was the first report about the enhancement of DHA production by osmotic regulation and this work provided two novel osmotic control processes for high lipid yield and high DHA percentage in total fatty acids. PMID- 26350998 TI - The discriminatory value of cardiorespiratory interactions in distinguishing awake from anaesthetised states: a randomised observational study. AB - Depth of anaesthesia monitors usually analyse cerebral function with or without other physiological signals; non-invasive monitoring of the measured cardiorespiratory signals alone would offer a simple, practical alternative. We aimed to investigate whether such signals, analysed with novel, non-linear dynamic methods, would distinguish between the awake and anaesthetised states. We recorded ECG, respiration, skin temperature, pulse and skin conductivity before and during general anaesthesia in 27 subjects in good cardiovascular health, randomly allocated to receive propofol or sevoflurane. Mean values, variability and dynamic interactions were determined. Respiratory rate (p = 0.0002), skin conductivity (p = 0.03) and skin temperature (p = 0.00006) changed with sevoflurane, and skin temperature (p = 0.0005) with propofol. Pulse transit time increased by 17% with sevoflurane (p = 0.02) and 11% with propofol (p = 0.007). Sevoflurane reduced the wavelet energy of heart (p = 0.0004) and respiratory (p = 0.02) rate variability at all frequencies, whereas propofol decreased only the heart rate variability below 0.021 Hz (p < 0.05). The phase coherence was reduced by both agents at frequencies below 0.145 Hz (p < 0.05), whereas the cardiorespiratory synchronisation time was increased (p < 0.05). A classification analysis based on an optimal set of discriminatory parameters distinguished with 95% success between the awake and anaesthetised states. We suggest that these results can contribute to the design of new monitors of anaesthetic depth based on cardiovascular signals alone. PMID- 26351000 TI - Location-specific nanoplasmonic sensing of biomolecular binding to lipid membranes with negative curvature. AB - The biochemical processes of cell membranes are sensitive to the geometry of the lipid bilayer. We show how plasmonic "nanowells" provide label-free real-time analysis of molecules on membranes with detection of preferential binding at negative curvature. It is demonstrated that norovirus accumulate in invaginations due to multivalent interactions with glycosphingolipids. PMID- 26351001 TI - Effects of age and acute muscle fatigue on reactive postural control in healthy adults. AB - BACKGROUND: Falls can cause moderate to severe injuries such as hip fractures and head trauma in older adults. While declines in muscle strength and sensory function contribute to increased falls in older adults, skeletal muscle fatigue is often overlooked as an additional contributor to fall risk. The purpose of this investigation was to examine the effects of acute lower extremity muscle fatigue and age on reactive postural control in healthy adults. METHODS: A sample of 16 individuals participated in this study (8 healthy older adults and 8 healthy young persons). Whole body kinematic and kinetic data were collected during anterior and posterior reproducible fall tests before (T0) and immediately after (T1) eccentric muscle fatiguing exercise, as well as after 15-min (T15) and 30-min (T30) of rest. FINDINGS: Lower extremity joint kinematics of the stepping limb during the support (landing) phase of the anterior fall were significantly altered by the presence of acute muscle fatigue. Step velocity was significantly decreased during the anterior falls. Statistically significant main effects of age were found for step length in both fall directions. Effect sizes for all outcomes were small. No statistically significant interaction effects were found. INTERPRETATION: Muscle fatigue has a measurable effect on lower extremity joint kinematics during simulated falls. These alterations appear to resolve within 15 min of recovery. The above deficits, coupled with a reduced step length, may help explain the increased fall risk in older adults. PMID- 26351002 TI - Influence of sagittal and axial types of ossification of posterior longitudinal ligament on mechanical stress in cervical spinal cord: A finite element analysis. AB - BACKGROUND: There are few studies focusing on the prediction of stress distribution according to the types of ossification of the posterior longitudinal ligament, which can be fundamental information associated with clinical aspects such as the relationship between stress level and neurological symptom severity. In this study, the influence of sagittal and axial types of ossification of the posterior longitudinal ligament on mechanical stress in the cervical spinal cord was investigated. METHODS: A three-dimensional finite element model of the cervical spine with spinal cord was developed and validated. The von Mises stresses in the cord and the reduction in cross-sectional areas and volume of the cord were investigated for various axial and sagittal types according to the occupying ratio of ossification of the posterior longitudinal ligament in the spinal canal. FINDINGS: The influence of axial type was less than that of the sagittal type, even though the central type showed higher maximum stresses in the cord, especially for the continuous type. With a 60% occupying ratio of ossification of the posterior longitudinal ligament, the maximum stress was significantly high and the cross-sectional area of the spinal cord was reduced by more than 30% of the intact area regardless of sagittal or axial types. Finally, a higher level of sagittal extension would increase the peak cord tissue stress, which would be related to the neurological dysfunction and tissue damage. INTERPRETATION: Quantitative investigation of biomechanical characteristics such as mechanical stress may provide fundamental information for pre-operative planning of treatment for ossification of the posterior longitudinal ligament. PMID- 26351003 TI - A Picture Really is Worth a Thousand Words: Public Engagement with the National Cancer Institute on Social Media. AB - The National Cancer Institute (NCI) provides pertinent information about cancer prevention, treatment, and research advancements that is considered objective and accurate. NCI's presence on social media is an example of a growing effort in promoting and facilitating audience engagement with evidence-based information about health and cancer. However, it is unknown what strategies are most effective for engaging audiences via this communication platform. To evaluate this important question, we analyzed data on posts, associated comments, and meta data from official NCI Facebook page between July 2010 and February 2015 (end of data collection). Results show that audience engagement is associated with the format of cancer-related social media posts. Specifically, posts with photos received significantly more likes, comments, and shares than videos, links, and status updates. The findings have important implications for how social media can be more effectively utilized to promote public engagement with important public health issues. PMID- 26351004 TI - Cavity-based architecture to preserve quantum coherence and entanglement. AB - Quantum technology relies on the utilization of resources, like quantum coherence and entanglement, which allow quantum information and computation processing. This achievement is however jeopardized by the detrimental effects of the environment surrounding any quantum system, so that finding strategies to protect quantum resources is essential. Non-Markovian and structured environments are useful tools to this aim. Here we show how a simple environmental architecture made of two coupled lossy cavities enables a switch between Markovian and non Markovian regimes for the dynamics of a qubit embedded in one of the cavity. Furthermore, qubit coherence can be indefinitely preserved if the cavity without qubit is perfect. We then focus on entanglement control of two independent qubits locally subject to such an engineered environment and discuss its feasibility in the framework of circuit quantum electrodynamics. With up-to-date experimental parameters, we show that our architecture allows entanglement lifetimes orders of magnitude longer than the spontaneous lifetime without local cavity couplings. This cavity-based architecture is straightforwardly extendable to many qubits for scalability. PMID- 26351006 TI - A Gathering of Native American Healers: Exploring the Interface of Indigenous Tradition and Professional Practice. AB - This article reports insights from a 4-day Gathering of Native American Healers at the University of Michigan in October of 2010. This event convened 18 traditional healers, clinically trained service providers, and cross-cultural mental health researchers for a structured group dialogue to advance professional knowledge about the integration of Indigenous healing practices and conventional mental health treatments in community-based mental health services for Native Americans. Our thematic analysis of transcripts from five Roundtable sessions afforded several key insights and understandings pertaining to the integration of Indigenous healing and conventional mental health services. First, with reference to traditional healing, the importance of a rampant relationality, various personal qualities, Indigenous spirituality, and maintenance of traditional life and culture were accentuated by Roundtable participants. Second, for traditional healers to practice effectively, Roundtable participants posited that these individuals must maintain personal wellness, cultivate profound knowledge of healing practices, recognize the intrinsic healing potential within all human beings, and work for the community rather than themselves. In speaking to the possibilities and challenges of collaboration between Indigenous and conventional biomedical therapeutic approaches, Roundtable participants recommended the implementation of cultural programming, the observance of mutuality and respect, the importance of clear and honest communication, and the need for awareness of cultural differences as unique challenges that must be collaboratively overcome. PMID- 26351005 TI - Flavins secreted by roots of iron-deficient Beta vulgaris enable mining of ferric oxide via reductive mechanisms. AB - Iron (Fe) is abundant in soils but generally poorly soluble. Plants, with the exception of Graminaceae, take up Fe using an Fe(III)-chelate reductase coupled to an Fe(II) transporter. Whether or not nongraminaceous species can convert scarcely soluble Fe(III) forms into soluble Fe forms has deserved little attention so far. We have used Beta vulgaris, one among the many species whose roots secrete flavins upon Fe deficiency, to study whether or not flavins are involved in Fe acquisition. Flavins secreted by Fe-deficient plants were removed from the nutrient solution, and plants were compared with Fe-sufficient plants and Fe-deficient plants without flavin removal. Solubilization of a scarcely soluble Fe(III)-oxide was assessed in the presence or absence of flavins, NADH (nicotinamide adenine dinucleotide, reduced form) or plant roots, and an Fe(II) trapping agent. The removal of flavins from the nutrient solution aggravated the Fe deficiency-induced leaf chlorosis. Flavins were able to dissolve an Fe(III) oxide in the presence of NADH. The addition of extracellular flavins enabled roots of Fe-deficient plants to reductively dissolve an Fe(III)-oxide. We concluded that root-secretion of flavins improves Fe nutrition in B. vulgaris. Flavins allow B. vulgaris roots to mine Fe from Fe(III)-oxides via reductive mechanisms. PMID- 26351007 TI - Label-free high-throughput detection and content sensing of individual droplets in microfluidic systems. AB - This study reports a microwave-microfluidics integrated approach capable of performing droplet detection at high-throughput as well as content sensing of individual droplets without chemical or physical intrusion. The sensing system consists of a custom microwave circuitry and a spiral-shaped microwave resonator that is integrated with microfluidic chips where droplets are generated. The microwave circuitry is very cost effective by using off-the-shelf components only. It eliminates the need for bulky benchtop equipment, and provides a compact, rapid and sensitive tool compatible for Lab-on-a-Chip (LOC) platforms. To evaluate the resonator's sensing capability, it was first applied to differentiate between single-phase fluids which are aqueous solutions with different concentrations of glucose and potassium chloride respectively by measuring its reflection coefficient as a function of frequency. The minimum concentration assessed was 0.001 g ml(-1) for potassium chloride and 0.01 g ml( 1) for glucose. In the droplet detection experiments, it is demonstrated that the microwave sensor is able to detect droplets generated at as high throughput as 3.33 kHz. Around two million droplets were counted over a period of ten minutes without any missing. For droplet sensing experiments, pairs of droplets that were encapsulated with biological materials were generated alternatively in a double T junction configuration and clearly identified by the microwave sensor. The sensed biological materials include fetal bovine serum, penicillin antibiotic mixture, milk (2% mf) and d-(+)-glucose. This system has significant advantages over optical detection methods in terms of its cost, size and compatibility with LOC settings and also presents significant improvements over other electrical-based detection techniques in terms of its sensitivity and throughput. PMID- 26351008 TI - Validity of ABCD Rule of Dermoscopy in Clinical Practice. AB - The ABCD rule of dermoscopy was developed to facilitate the dermoscopic differentiation between benign and malignant melanocytic lesions. However, there is a lack of studies on its validity in clinical practice. The aim of this study was to evaluate the accuracy of the algorithm used bedside, compared with the accuracy of the preliminary preoperative diagnosis, and to rate physicians' level of confidence in the diagnosis. Melanocytic tumours were preoperatively scored bedside, according to the ABCD algorithm; 309 cases (46 melanomas and 263 naevi) were included. A sensitivity of 83% and specificity of 45% were found for the ABCD algorithm. A comparable sensitivity (74%), but a significantly higher specificity (91%), was found for the preliminary diagnosis. Interestingly, there was a considerable percentage (19.6%) of early melanomas for which a malignant diagnosis was not preoperatively expected, indicating that it is important to maintain generous indications for excision or to practise short-term follow-up of ambiguous lesions in order to detect early melanomas. PMID- 26351009 TI - Psychosocial Pain Management Moderation: The Limit, Activate, and Enhance Model. AB - There is a growing emphasis in the pain literature on understanding the following second-order research questions: Why do psychosocial pain treatments work? For whom do various treatments work? This critical review summarizes research that addresses the latter question and proposes a moderation model to help guide future research. A theoretical moderation framework for matching individuals to specific psychosocial pain interventions has been lacking. However, several such frameworks have been proposed in the broad psychotherapy and implementation science literature. Drawing on these theories and adapting them specifically for psychosocial pain treatment, here we propose a Limit, Activate, and Enhance model of pain treatment moderation. This model is unique in that it includes algorithms not only for matching treatments on the basis of patient weaknesses but also for directing patients to interventions that build on their strengths. Critically, this model provides a basis for specific a priori hypothesis generation, and a selection of the possible hypotheses drawn from the model are proposed and discussed. Future research considerations are presented that could refine and expand the model based on theoretically driven empirical evidence. PERSPECTIVE: The Limit, Activate, and Enhance model presented here is a theoretically derived framework that provides an a priori basis for hypothesis generation regarding psychosocial pain treatment moderators. The model will advance moderation research via its unique focus on matching patients to specific treatments that (1) limit maladaptive responses, (2) activate adaptive responses, and (3) enhance treatment outcomes based on patient strengths and resources. PMID- 26351010 TI - Loading-induced changes on topographical distributions of the zonal properties of osteoarthritic tibial cartilage--A study by magnetic resonance imaging at microscopic resolution. AB - The topographical distributions of the zonal properties of articular cartilage over the medial tibia from an experimental osteoarthritis (OA) model were evaluated as a function of external loading by microscopic Magnetic Resonance Imaging (uMRI). T2 relaxation times and cartilage thicknesses were measured at 17.6 um resolution from 118 specimens, which came from thirteen dogs (six 8-week and seven 12-week after surgery), with and without mechanical loading. In addition, bulk mechanical modulus was measured topographically from each tibia surface. The total thickness decreased significantly under the external loading, in which the relative thickness of the superficial zone (SZ) and the transitional zone (TZ) increased whereas the radial zones (RZs) decreased. In the bulk data, T2(55 degrees ) decreased significantly (p<0.001) at all OA-time-points, but T2(0 degrees ) decreased without significance (p>0.05) at 8-week. Complex relationships were found in the zonal tissue properties as a function of external loading with the progress of OA. T2 in the superficial zone changed more profoundly than the same properties in the radial zone as a function of external loading at all OA time-points. This study confirms that OA affects the load induced changes in the molecular distribution and structure of cartilage, which are both depth-dependent and topographically distributed. Such detailed knowledge of mechanobiological changes in specific tibial cartilage zones and locations with OA progress could improve the early detection of the subtle softening of cartilage that accompanies pre-clinical stages of OA. PMID- 26351012 TI - Associations between feed efficiency, sexual maturity and fertility-related measures in young beef bulls. AB - The beef industry has emphasized the improvement of feed utilization, as measured by modeling feed intake through performance traits to calculate residual feed intake (RFI). Evidence supports an inverse relationship between feed efficiency and reproductive function. The objective of this study was to determine the relationship of reproductive assessments and RFI unadjusted (RFI(Koch)) or adjusted for body composition (RFI(us)) and the relationship among fertility related parameters. In total, 34 crossbred bulls were housed together for 112 days of performance evaluation, followed by assessment of scrotum IR imaging, scrotal circumference, testes ultrasonography and semen quality parameters at 377+/-33.4 days of age. Bulls were slaughtered at 389+/-34.0 days of age, and analyses of carcass composition, biometrics and histomorphometry of the testis and epididymis were conducted. Bulls were grouped into two subpopulations based on divergence of RFI, and within each RFI model either by including 50% of the population (Halves, high and low RFI, n=17) or 20.6% extremes of the population (Tails, high and low RFI, n=7). The means of productive performance and fertility related measures were compared through these categories. Pearson's correlation was calculated among fertility-related measures. In the Halves subpopulation of the RFI(us), sperm of low-RFI bulls had decreased progressive motility (47.30% v. 59.90%) and higher abundance of tail abnormalities (4.30% v. 1.80%) than that of high-RFI bulls. In the Tails subpopulation of the RFI(Koch), low RFI displayed less variation in the scrotum surface temperature (0.62 degrees C v. 1.16 degrees C), decreased testis echogenicity (175.50 v 198.00 pixels) and larger (60.90 v. 56.80 mm(2)) but less-developed seminiferous tubules than high-RFI bulls. The evaluation of fertility-related parameters indicated that a higher percentage of immature seminiferous tubules was correlated with occurrence of sperm with distal droplets (r=0.59), a larger temperature variation at the top of the scrotum was correlated with improved sperm progressive motility (r=0.38), a lower occurrence of sperm loose head abnormalities was correlated with larger temperature variation at the lower part of the scrotum (r=-0.43), and a lower minimum testis echogenicity (r=-0.59) and smaller scrotal circumference (r=0.72) were correlated with age. The adjustment for body composition (RFI determination) enabled distinct biological inferences about reproduction and feed efficiency when compared with the non-adjusted model. However, both RFI models and the correlation analysis supported the hypothesis that feed-efficient bulls have features of delayed sexual maturity. Overall, the assessment of fertility-related measurements is important to avoid the improvement of feed efficiency at the expense of reproductive function in young bulls. PMID- 26351011 TI - Effectiveness of Fixed-Dose Perindopril/Amlodipine on Clinic, Ambulatory and Self Monitored Blood Pressure and Blood Pressure Variability: An Open-Label, Non Comparative Study in the General Practice. AB - INTRODUCTION: Fixed-dose combinations (FDCs) of antihypertensive agents improve therapeutic efficacy, according to current guidelines and large clinical studies. AIM: This Russian study examined the effect on blood pressure (BP) of substituting current ineffective antihypertensive treatment with FDC perindopril/amlodipine in patients with uncontrolled hypertension. METHODS: BP was measured in the doctor's office at each visit, daily at home, and by ambulatory monitoring (ABPM) at inclusion and end-of-study. RESULTS: Ninety patients (52.7 +/- 12.2 years old; mean baseline BP 161.4/94.9 mmHg) at high or very high cardiovascular risk were included. FDC perindopril/amlodipine (5/5, 10/5 or 10/10 mg) exerted a rapid (2 weeks) and significant (p < 0.001) reduction in clinic BP, maintained after 3 months (-33.7/17.1 mmHg). ABPM and home monitoring showed that BP decrease remained significant throughout the study (p < 0.0001). BP variability was reduced, indicating the stable and homogeneous 24-h antihypertensive effect of FDC perindopril/amlodipine. Quality of life and adherence were also improved. CONCLUSIONS: The three main methods of BP assessment showed that substituting ineffective antihypertensive therapy with FDC perindopril/amlodipine resulted in a rapid and pronounced antihypertensive effect, with target BP levels achieved after 3 months in most patients. This beneficial effect was observed also on various parameters related to BP variability, which may reflect additional cardioprotective properties. PMID- 26351013 TI - Comparison of various hours living fission products for absolute power density determination in VVER-1000 mock up in LR-0 reactor. AB - Measuring power level of zero power reactor is a quite difficult task. Due to the absence of measurable cooling media heating, it is necessary to employ a different method. The gamma-ray spectroscopy of fission products induced within reactor operation is one of possible ways of power determination. The method is based on the proportionality between fission product buildup and released power. The (92)Sr fission product was previously preferred as nuclide for LR-0 power determination for short-time irradiation experiments. This work aims to find more appropriate candidates, because the (92)Sr, however suitable, has a short half life, which limits the maximal measurable amount of fuel pins within a single irradiation batch. The comparison of various isotopes is realized for (92)Sr, (97)Zr, (135)I, (91)Sr, and (88)Kr. The comparison between calculated and experimentally determined (C/E-1 values) net peak areas is assessed for these fission products. Experimental results show that studied fission products, except (88)Kr, are in comparable agreement with (92)Sr results. Since (91)Sr has notably higher half-life than (92)Sr, (91)Sr seems to be more appropriate marker in experiments with a large number of measured fuel pins. PMID- 26351015 TI - Introduction: Frontiers in Organic Synthesis. PMID- 26351014 TI - Evaluation of IDH1G105 polymorphism as prognostic marker in intermediate-risk AML. AB - Germline polymorphisms in genes mutated in acute myeloid leukemia (AML) may have prognostic impact. Therefore, the relevance of the polymorphism IDH1G105 (IDH1105(GGT) minor allele) was evaluated in the context of concomitant molecular mutations in a cohort of 507 AML cases with intermediate-risk cytogenetics. In addition, a cohort of 475 healthy controls was analyzed for this polymorphism. IDH1105(GGT) minor allele was found in 10 % of AML patients and 9 % of healthy controls. While no differences were seen with regard to cytomorphology or cytogenetics, immunophenotyping revealed significantly reduced expression of the progenitor marker CD34 in AML cases harboring IDH1105(GGT) minor allele. Cases with IDH1105(GGT) minor allele as compared to those with the IDH1105(GGC) major allele had significantly longer event-free survival (EFS) (median 16 vs 11 months, p = 0.013) which was most pronounced in the age group >60 years (median 14 vs 9 months, p = 0.007) and in the NPM1 mutated/FLT3-ITD/FLT3wt ratio <0.5 group (median 61 vs 13 months, p = 0.012). However, this association is not independent of other prognostic parameters, and we conclude that IDH1105(GGT) minor allele has to be considered in the context of the genetic background of the individual AML analyzed. PMID- 26351016 TI - Oogenesis in Laetacara araguaiae (Ottoni and Costa, 2009) (Labriformes: Cichlidae). AB - We aimed to analyze the oogenesis of adult females of the cichlid fish Laetacara araguaiae. The specimens' gonads were removed and processed for light and transmission electron microscopy. Oogenesis in L. araguaiae showed the following characteristics: a germinal epithelium with three types of oogonia (A undifferentiated, A-differentiated and B-oogonia), oocytes at meiotic prophase stage and ovarian follicle formation. Oocytes showing primary growth with pre vitellogenic and cortical alveolus were observed. Similar to data for other cichlids, oocytes in secondary growth or vitellogenesis were characterized by the initial deposition of yolk microgranules. The event that characterizes the maturation stage is nucleolus migration, also called the germinal vesicle, to the oocyte periphery in the direction of the micropyle. The follicular complex undergoes several changes throughout the oocyte stages. To the best of our knowledge this study is the first to describe L. araguaiae oogenesis. Moreover, this study is the first step to better understand the reproductive biology of this species, which shows great potential for use as an ornamental fish. PMID- 26351017 TI - Is It Daily, Monthly, or Yearly Blood Pressure Variability that Enhances Cardiovascular Risk? AB - Variability is a phenomenon common to most biological processes that we can measure and is a particular feature of blood pressure (BP). Variability causes concern for many physicians regarding its clinical meaning and potential impact on cardiovascular risk. In this review, we assess the role of different time periods of blood pressure variability (BPV) in cardiovascular risk stratification. We review the indices of BPV derived from ambulatory blood pressure measurement (ABPM), home blood pressure measurement (HBPM), or at the clinic setting with the intention of providing a clear message for clinical practice. BPV, either derived from ABPM or HBPM, does not consistently augment cardiovascular risk prediction over and beyond that of average BP, particularly in low-risk individuals. That said, it would seem that certain medications such as calcium channel blockers may have a beneficial effect on visit-to-visit BPV and perhaps reduce the associated cardiovascular risk. This highlights the benefits in using combination therapy which might couple a number of therapeutic benefits such as the reductions of mean blood pressure and BPV. Overall, we should remain aware that the average BP level remains the main modifiable risk factor derived from BP measurements and continue to improve the control of hypertension and adverse health outcomes. PMID- 26351018 TI - An optimized and versatile synthesis to pyridinylimidazole-type p38alpha mitogen activated protein kinase inhibitors. AB - An optimized strategy for the synthesis of the potent p38alpha mitogen-activated protein kinase inhibitors 2-(2-hydroxyethylsulfanyl)-4-(4-fluorophenyl)-5-(2 aminopyridin-4-yl)imidazole (3) and 2-(2,3-dihydroxypropylsulfanyl)-4-(4 fluorophenyl)-5-(2-aminopyridin-4-yl)imidazole (4) starting from 2-fluoro-4 methylpyridine is reported. In contrast to a previously published synthesis starting from 2-bromo-4-methylpyridine, the overall yield could be increased from 3.6% to 29.4%. Moreover, this strategy avoids the use of palladium as a catalyst and is more diverse and versatile. Using this optimized protocol, both enantiomers of potent inhibitor 3 were synthesized. Biological data demonstrated that the (S)-enantiomer is the two times more potent eutomer. PMID- 26351019 TI - Peritoneal mesothelioma in Italy: Trends and geography of mortality and incidence. AB - INTRODUCTION: Peritoneal mesothelioma, a very rare and lethal malignancy, has not been investigated as extensively as pleural mesothelioma, although the role of asbestos exposure in its occurrence is well-known. Data from Italy are relevant, as it was the largest European asbestos producer, and asbestos was widely used in many economic activities. METHODS: A population-based mortality and incidence analysis was performed in Italy. Data sources were the National Multiple-causes of-death Database (1995-2010) and the Italian Mesothelioma Register (1993-2008). RESULTS: We found an increasing trend of age standardized mortality rates in men, but no clear trend in women; moreover, we showed significant risks of death in several northern regions, formerly heavy asbestos users; finally, mortality/incidence ratios similar for both genders (about 0.8) were estimated. CONCLUSIONS: The study, based on national data, showed a higher risk of mortality from and incidence of peritoneal mesothelioma in areas with formerly heavy exposure to asbestos. PMID- 26351020 TI - A Review of Sleep Disorder Diagnosis by Electromyogram Signal Analysis. AB - Sleep and sleep-related problems play a role in a large number of human disorders and affect every field of medicine. It is estimated that 50 to 70 million Americans suffer from a chronic sleep disorder, which hinders their daily life, affects their health, and confers a significant economic burden to society. The negative public health consequences of sleep disorders are enormous and could have long-term effects, including increased risk of hypertension, diabetes, obesity, heart attack, stroke and in some cases death. Polysomnographic modalities can monitor sleep cycles to identify disrupted sleep patterns, adjust the treatments, increase therapeutic options and enhance the quality of life of recording the electroencephalogram (EEG), electromyogram (EMG) and electrocardiogram (ECG). Although the skills acquired by medical facilitators are quite extensive, it is just as important for them to have access to an assortment of technologies and to further improve their monitoring and treatment capabilities. Computer-aided analysis is one advantageous technique that could provide quantitative indices for sleep disorder screening. Evolving evidence suggests that Parkinson's disease may be associated with rapid eye movement sleep behavior disorder (RBD). With this article, we are reviewing studies that are related to EMG signal analysis for detection of neuromuscular diseases that result from sleep movement disorders. As well, the article describes the recent progress in analysis of EMG signals using temporal analysis, frequency-domain analysis, time-frequency, and sparse representations, followed by the comparison of the recent research. PMID- 26351021 TI - The Response of the Shoulder Complex to Repetitive Work: Implications for Workplace Design. AB - The shoulder complex has multiple degrees of freedom and muscular geometry that make it possible to complete tasks with many different kinematic and muscular strategies. Substantial research has investigated the effects of workplace factors (posture and task design) on the shoulder complex. The interactive relationships between workplace factors, however, make it challenging to synthesize the literature to make decisive conclusions regarding the impact of repetitive work. This review summarizes a broad selection of the literature examining the effects of repetitive work on the shoulder complex with respect to kinematic and muscular adaptation strategies to maintain task performance with muscular fatigue. The implications of repetitive work and workplace design on the shoulder complex are discussed. PMID- 26351022 TI - Strategies and Scientific Basis of Dose Reduction on State-of-the-Art Multirow Detector X-Ray CT Systems. AB - The continued development in multirow detector computed tomography (MDCT) technology accompanied by tremendous enhancement in the clinical utility and rapid increase in the number of MDCT scanners worldwide are causing a steep rise in the number of diagnostic computed tomography (CT) procedures performed each year. The everincreasing use of this X-radiation-based imaging technique has raised radiation protection concerns among the clinical community and general public. To address these concerns, significant efforts have been made by the clinical community as well as industry, research, and government organizations. Because of these efforts, modern MDCT systems are now equipped with a variety of tools that can lead to "radiation dose-optimized" CT images if used properly. This review describes CT dose metrics and their limitations, radiation dose reduction techniques and strategies implemented using modern MDCT scanners, and the role of research and regulatory organizations in developing guidelines and regulations to facilitate the adoption of the dose reduction strategies. An account of further developments required to achieve submillisievert X-ray CT doses and to make X-ray CT a radiation risk-free imaging modality is also given. A detailed description of the scientific basis and controversies surrounding the linear no threshold (LNT) model, which forms the basis of all radiation dose reduction strategies, is also provided in this review. According to the LNT model, there is no amount of radiation that is safe or beneficial for human beings. Based on recent epidemiological studies, despite all of the controversies, the LNT model continues to be the basis of the ALARA (as low as reasonably achievable) principle of radiation protection framework in CT. PMID- 26351023 TI - Microstimulation: Principles, Techniques, and Approaches to Somatosensory Neuroprosthesis. AB - The power of movement of electrically charged particles has been used to alleviate an array of illnesses and help control some human body parts. Microstimulation, the electrical current-driven excitation of neural elements, is now being aimed at brain-machine interfaces (BMIs), brain-controlled external devices that improve quality of life for people such as those who have lost the ability to use their limbs. This effort is motivated by behavioral experiments that indicate a direct link between microstimulation-induced sensory experience and behavior, pointing to the possibility of optimizing and controlling the outputs of BMIs. Several laboratories have focused on using electrical stimulation to return somatosensory feedback from prosthetic limbs directly to the user's central nervous system. However, the difficulty of the problem has led to limited success thus far, and there is a need for a better understanding of the basic principles of neural microstimulation. This article provides a review of the available literature and some recent work at Downstate Medical Center and Columbia University on microstimulation of the primate and rodent somatosensory (S1) cortex and the ventral posterolateral thalamus. It is aimed at contributing to the existing knowledge base to generate good behavioral responses and effective, BMI-appropriate somatosensory feedback. In general, the threshold for the particular brain tissue in response to current-amplitude has to be determined by rigorous experimentation. For consistently reproducible results, hardware and thresholds for microstimulation have to be specified. In addition, effects on motor functions, including unwanted side effects in response to the microstimulation of brain tissue, must be examined to take the field from bench to bedside. PMID- 26351024 TI - Prevalence of Apparent Therapy-Resistant Hypertension and Its Effect on Outcome in Patients With Chronic Kidney Disease. AB - New options recently became available for treatment of uncontrolled blood pressure. Information on the prevalence of therapy-resistant hypertension (TRH) in patients with chronic kidney disease and its consequences is relevant to balance risks and benefits of potential new therapies. Data of 788 patients with chronic kidney disease came from a multicenter study investigating the effect on outcome of an integrated multifactorial approach delivered by nurse practitioners added to usual care versus usual care alone. Blood pressure was measured at the office and during 30 minutes using an automated oscillometric device. Apparent TRH (aTRH) was defined as a blood pressure >=130/80 mm Hg despite treatment with >=3 antihypertensive drugs, including a diuretic or treatment with >=4 antihypertensive drugs. Participants were followed up for the occurrence of myocardial infarction, stroke or cardiovascular mortality (composite cardiovascular end point) and end-stage renal disease. aTRH was present in 34% (office blood pressure) and in 32% (automated measurements). During 5.3 years of follow-up, 17% of patients with aTRH reached a cardiovascular end point and 27% reached end-stage renal disease. aTRH lead to a 1.5-fold higher risk (95% confidence interval, 0.8-3.0) of a cardiovascular end point compared with controlled hypertensives in multivariable-adjusted analysis. aTRH increased end stage renal disease risk 2.3-fold (95% confidence interval, 1.4-3.7). During 4 years of follow-up, the prevalence of aTRH did not decline in either treatment group. The prevalence of aTRH is high in patients with chronic kidney disease even after optimization of nephrologist care. The presence of TRH is related to a substantially increased risk of renal and cardiovascular outcomes. PMID- 26351025 TI - Pentaerythritol Tetranitrate Targeting Myocardial Reactive Oxygen Species Production Improves Left Ventricular Remodeling and Function in Rats With Ischemic Heart Failure. AB - Reduced nitric oxide bioavailability contributes to progression of cardiac dysfunction and remodeling in ischemic heart failure. Clinical use of organic nitrates as nitric oxide donors is limited by development of nitrate tolerance and reactive oxygen species formation. We investigated the effects of long-term therapy with pentaerythritol tetranitrate (PETN), an organic nitrate devoid of tolerance, in rats with congestive heart failure after extensive myocardial infarction. Seven days after coronary artery ligation, rats were randomly allocated to treatment with PETN (80 mg/kg BID) or placebo for 9 weeks. Long-term PETN therapy prevented the progressive left ventricular dilatation and improved left ventricular contractile function and relaxation in rats with congestive heart failure. Mitochondrial superoxide anion production was markedly increased in the failing left ventricular myocardium and nearly normalized by PETN treatment. Gene set enrichment analysis revealed that PETN beneficially modulated the dysregulation of mitochondrial genes involved in energy metabolism, paralleled by prevention of uncoupling protein-3, thioredoxin-2, and superoxide dismutase-2 downregulation. Moreover, PETN provided a remarkable protective effect against reactive fibrosis in chronically failing hearts. Mechanistically, induction of heme oxygenase-1 by PETN prevented mitochondrial superoxide generation, NOX4 upregulation, and ensuing formation of extracellular matrix proteins in fibroblasts from failing hearts. In summary, PETN targeting reactive oxygen species generation prevented the changes of mitochondrial antioxidant enzymes and progressive fibrotic remodeling, leading to amelioration of cardiac functional performance. Therefore, PETN might be a promising therapeutic option in the treatment of ischemic heart diseases involving oxidative stress and impairment in nitric oxide bioactivity. PMID- 26351026 TI - Aerobic Exercise Training in Formerly Preeclamptic Women: Effects on Venous Reserve. AB - In women with a history of preeclampsia, low plasma volume (<=1373 mL/m(2)) is associated with recurrent preeclampsia and chronic hypertension. Interventions that improve volume reserve may reduce these risks in formerly preeclamptic women. In this study, we examined the effects of aerobic exercise training on venous reserves in 24 normotensive formerly preeclamptic women and 20 controls. Before and after 12-week aerobic exercise training, we measured plasma volume with albumin indicator dilution technique and venous compliance with venous occlusion plethysmography. Venous compliance and hemodynamic responses were assessed dynamically during graded head-up tilt (HUT). Formerly preeclamptic women had lower pretraining plasma volume and venous compliance than controls (1348+/-78 versus 1529+/-112 mL/m(2); P<0.01 and 0.04+/-0.02 versus 0.07+/-0.01 mL.dL(-1).mm Hg(-1); P<0.01, respectively). Blood pressure decreased comparably between groups in response to HUT (P=0.11); the increase in heart rate in response to HUT was however more pronounced in preeclamptic women than in controls (P=0.01) Training increased plasma volume comparably in both groups (+180 versus +135 mL/m(2), P=0.22) and similarly physical fitness (+3.4 and +3.7 mL.min(-1).kg(-1), P=0.43). Venous compliance increased twice as much in formerly preeclamptic women than in controls (supine +0.02 versus +0.01 mL.dL(-1).mm Hg( 1); P<0.01). After training, HUT decreased mean blood pressure comparable with pretraining responses in both groups, whereas both groups fulfilled the HUT testing at a persistently lower heart rate. These results demonstrate that 12 weeks of aerobic exercise training improve venous reserve in postpartum women. Training normalized plasma volume and venous compliance in formerly preeclamptic women to pretraining levels of controls. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00900458. PMID- 26351027 TI - Blood Pressure Is Not Associated With Cerebral Blood Flow in Older Persons. AB - Many studies showing a relation between low blood pressure (BP) and adverse health outcomes in older persons suggest that low BP gives rise to reduced cerebral blood flow (CBF). However, limited evidence is available about this association. Baseline data of 203 participants in the Discontinuation of Antihypertensive Treatment in the Elderly (DANTE) trial were used (mean age, 81 years, using antihypertensive medication and with mild cognitive deficits). BP, BP changes on standing, and CBF derived from pseudo-continuous arterial spin labeling magnetic resonance imaging were assessed in all participants. In 102 participants who were randomly assigned to 4-month continuation (n=47) or discontinuation of antihypertensive treatment (n=55), BP and CBF change were evaluated at 4-month follow-up. Systolic and diastolic BP were not associated with CBF (B=-0.21, P=0.50 and B=-1.07, P=0.07), neither were mean arterial pressure, pulse pressure, and BP changes on standing. In subgroups of participants with small vessel-related cerebral pathologies, including high white matter hyperintensity volume, microbleeds, and lacunar infarcts, or in participants with lower cognition or diabetes mellitus, no association was found between any BP parameters and CBF. Furthermore, compared to the continuation group, CBF change at 4 months was not different in the discontinuation group (B= 0.12, P=0.23). Contrary to the notion that lower BP in old age is associated with decreased CBF, our data do not show this association in older persons using antihypertensive medication and with mild cognitive deficits. Also, this association was not present in subgroups of more vulnerable persons, reflected by small vessel-related cerebral pathologies, lower cognition, or diabetes mellitus. PMID- 26351028 TI - Different Somatic Mutations in Multinodular Adrenals With Aldosterone-Producing Adenoma. AB - Primary aldosteronism is the most common form of secondary hypertension. Somatic mutations in KCNJ5, ATP1A1, ATP2B3, and CACNA1D are found in aldosterone producing adenoma. In addition, adrenals with aldosterone-producing adenomas show cortical remodeling and frequently multiple secondary nodules. Our aim was to investigate whether different aldosterone-producing nodules from the same adrenal share the same mutational status. Aldosterone synthase expression was assessed in multinodular adrenals from 27 patients. DNA of 37 aldosterone-producing secondary nodules was extracted from formalin-fixed paraffin-embedded tissues and genotyped for KCNJ5, ATP1A1, ATP2B3, and CACNA1D mutations. Among 17 adrenals with a somatic mutation in the principal nodule, 4 showed the same mutation in a secondary nodule, whereas 10 had no mutation in any of the known genes. In 1 adrenal harboring the KCNJ5 p.Gly151Arg mutation in the principal nodule, the same mutation was present in 2 secondary nodules, but no mutation was found in a third nodule. Finally, in 2 adrenals with a CACNA1D mutation in the principal nodule, a KCNJ5 mutation was identified in the secondary nodule. Among 10 adrenals without mutations in the principal nodule, 1 carried a KCNJ5 mutation in the secondary nodule. No mutations were detected in 7 aldosterone-producing cell clusters from 6 adrenals. No association was observed between the presence of mutations in secondary nodules and clinical parameters. In conclusion, different mutations are found in different aldosterone-producing nodules from the same adrenal, suggesting that somatic mutations are independent events triggered by mechanisms that remain to be identified. PMID- 26351029 TI - Organic Nitrates in Heart Failure Revisited: Pentaerythritol Tetranitrate Induces Heme Oxygenase 1 to Protect the Myocardium. PMID- 26351030 TI - Obligatory Role for B Cells in the Development of Angiotensin II-Dependent Hypertension. AB - Clinical hypertension is associated with raised serum IgG antibodies. However, whether antibodies are causative agents in hypertension remains unknown. We investigated whether hypertension in mice is associated with B-cell activation and IgG production and moreover whether B-cell/IgG deficiency affords protection against hypertension and vascular remodeling. Angiotensin II (Ang II) infusion (0.7 mg/kg per day; 28 days) was associated with (1) a 25% increase in the proportion of splenic B cells expressing the activation marker CD86, (2) an 80% increase in splenic plasma cell numbers, (3) a 500% increase in circulating IgG, and (4) marked IgG accumulation in the aortic adventitia. In B-cell-activating factor receptor-deficient (BAFF-R(-/-)) mice, which lack mature B cells, there was no evidence of Ang II-induced increases in serum IgG. Furthermore, the hypertensive response to Ang II was attenuated in BAFF-R(-/-) (Delta30+/-4 mm Hg) relative to wild-type (Delta41+/-5 mm Hg) mice, and this response was rescued by B-cell transfer. BAFF-R(-/-) mice displayed reduced IgG accumulation in the aorta, which was associated with 80% fewer aortic macrophages and a 70% reduction in transforming growth factor-beta expression. BAFF-R(-/-) mice were also protected from Ang II-induced collagen deposition and aortic stiffening (assessed by pulse wave velocity analysis). Finally, like BAFF-R deficiency, pharmacological depletion of B cells with an anti-CD20 antibody attenuated Ang II induced hypertension by ~35%. Hence, these studies demonstrate that B cells/IgGs are crucial for the development of Ang II-induced hypertension and vessel remodeling in mice. Thus, B-cell-targeted therapies-currently used for autoimmune diseases-may hold promise as future treatments for hypertension. PMID- 26351031 TI - Galectin-3 Participates in Cardiovascular Remodeling Associated With Obesity. AB - Remodeling, diastolic dysfunction, and arterial stiffness are some of the alterations through which obesity affects the cardiovascular system. Fibrosis and inflammation are important mechanisms underlying cardiovascular remodeling, although the precise promoters involved in these processes are still unclear. Galectin-3 (Gal-3) induces inflammation and fibrosis in the cardiovascular system. We have investigated the potential role of Gal-3 in cardiac damage in morbidly obese patients, and we have evaluated the protective effect of the Gal-3 inhibition in the occurrence of cardiovascular fibrosis and inflammation in an experimental model of obesity. Morbid obesity is associated with alterations in cardiac remodeling, mainly left ventricular hypertrophy and diastolic dysfunction. Obesity and hypertension are the main determinants of left ventricular hypertrophy. Insulin resistance, left ventricular hypertrophy, and circulating levels of C-reactive protein and Gal-3 are associated with a worsening of diastolic function in morbidly obese patients. Obesity upregulates Gal-3 production in the cardiovascular system in a normotensive animal model of diet-induced obesity by feeding for 6 weeks a high-fat diet (33.5% fat). Gal-3 inhibition with modified citrus pectin (100 mg/kg per day) reduced cardiovascular levels of Gal-3, total collagen, collagen I, transforming and connective growth factors, osteopontin, and monocyte chemoattractant protein-1 in the heart and aorta of obese animals without changes in body weight or blood pressure. In morbidly obese patients, Gal-3 levels are associated with diastolic dysfunction. In obese animals, Gal-3 blockade decreases cardiovascular fibrosis and inflammation. These data suggest that Gal-3 could be a novel therapeutic target in cardiac fibrosis and inflammation associated with obesity. PMID- 26351032 TI - Cardiomyocyte Mineralocorticoid Receptor Activation Impairs Acute Cardiac Functional Recovery After Ischemic Insult. AB - Loss of mineralocorticoid receptor signaling selectively in cardiomyocytes can ameliorate cardiac fibrotic and inflammatory responses caused by excess mineralocorticoids. The aim of this study was to characterize the role of cardiomyocyte mineralocorticoid receptor signaling in ischemia-reperfusion injury and recovery and to identify a role of mineralocorticoid receptor modulation of cardiac function. Wild-type and cardiomyocyte mineralocorticoid receptor knockout mice (8 weeks) were uninephrectomized and maintained on (1) high salt (0.9% NaCl, 0.4% KCl) or (2) high salt plus deoxycorticosterone pellet (0.3 mg/d, 0.9% NaCl, 0.4% KCl). After 8 weeks of treatment, hearts were isolated and subjected to 20 minutes of global ischemia plus 45 minutes of reperfusion. Mineralocorticoid excess increased peak contracture during ischemia regardless of genotype. Recovery of left ventricular developed pressure and rates of contraction and relaxation post ischemia-reperfusion were greater in knockout versus wild-type hearts. The incidence of arrhythmic activity during early reperfusion was significantly higher in wild-type than in knockout hearts. Levels of autophosphorylated Ca(2+)/calmodulin protein kinase II (Thr287) were elevated in hearts from wild-type versus knockout mice and associated with increased sodium hydrogen exchanger-1 expression. These findings demonstrate that cardiomyocyte specific mineralocorticoid receptor-dependent signaling contributes to electromechanical vulnerability in acute ischemia-reperfusion via a mechanism involving Ca(2+)/calmodulin protein kinase II activation in association with upstream alteration in expression regulation of the sodium hydrogen exchanger-1. PMID- 26351034 TI - Fabricating and Tailoring Polyaniline (PANI) Nanofibers with High Aspect Ratio in a Low-Acid Environment in a Magnetic Field. AB - In a 0.010 m HCl solution, we successfully transformed irregular polyaniline (PANI) agglomerates into uniform PANI nanofibers with a diameter of 46-145 nm and a characteristic length on the order of several microns by the addition of superparamagnetic Fe3 O4 microspheres in a magnetic field. The PANI morphological evolution showed that the PANI nanofibers stemmed from the PANI coating shell synthesized on the surface of the Fe3 O4 microsphere chains. It was found that the magnetic field could optimize the PANI nanofibers with a narrow diameter size distribution, and effectively suppressed secondary growth. When compared with other microspheres (like silica and polystyrene), only the use of superparamagnetic Fe3 O4 microspheres resulted in the appearance of PANI nanofibers. Attempts to form these high-quality PANI nanofibers in other concentrations of HCl solution were unsuccessful. This deficiency was largely attributed to the inappropriate quantity of aniline cations. PMID- 26351033 TI - Endothelial Mineralocorticoid Receptors Differentially Contribute to Coronary and Mesenteric Vascular Function Without Modulating Blood Pressure. AB - Arteriolar vasoreactivity tightly regulates tissue-specific blood flow and contributes to systemic blood pressure (BP) but becomes dysfunctional in the setting of cardiovascular disease. The mineralocorticoid receptor (MR) is known to regulate BP via the kidney and by vasoconstriction in smooth muscle cells. Although endothelial cells (EC) express MR, the contribution of EC-MR to BP and resistance vessel function remains unclear. To address this, we created a mouse with MR specifically deleted from EC (EC-MR knockout [EC-MR-KO]) but with intact leukocyte MR expression and normal renal MR function. Telemetric BP studies reveal no difference between male EC-MR-KO mice and MR-intact littermates in systolic, diastolic, circadian, or salt-sensitive BP or in the hypertensive responses to aldosterone+/-salt or angiotensin II+/-l-nitroarginine methyl ester. Vessel myography demonstrated normal vasorelaxation in mesenteric and coronary arterioles from EC-MR-KO mice. After exposure to angiotensin II-induced hypertension, impaired endothelial-dependent relaxation was prevented in EC-MR-KO mice in mesenteric vessels but not in coronary vessels. Mesenteric vessels from angiotensin II-exposed EC-MR-KO mice showed increased maximum responsiveness to acetylcholine when compared with MR-intact vessels, a difference that is lost with indomethacin+l-nitroarginine methyl ester pretreatment. These data support that EC-MR plays a role in regulating endothelial function in hypertension. Although there was no effect of EC-MR deletion on mesenteric vasoconstriction, coronary arterioles from EC-MR-KO mice showed decreased constriction to endothelin-1 and thromboxane agonist at baseline and also after exposure to hypertension. These data support that EC-MR participates in regulation of vasomotor function in a vascular bed-specific manner that is also modulated by risk factors, such as hypertension. PMID- 26351035 TI - Dual energy imaging and intracycle motion correction for CT coronary angiography in patients with intermediate to high likelihood of coronary artery disease. AB - We explored whether intracycle motion correction algorithms (MCAs) might be applicable to dual energy computed tomography coronary angiography in patients with intermediate to high likelihood of coronary artery disease. MCA reconstructions were associated with higher interpretability rates (96.7% vs. 87.9%, P<.001), image quality scores (4.12 +/- 0.9 vs. 3.76 +/- 1.0; P<.0001), and diagnostic performance [area under the curve of 0.95 (95% confidence interval [CI] 0.92-0.97) vs. 0.89 (95% CI 0.86-0.92); P<.0001] compared to conventional reconstructions. In conclusion, application of intracycle MCA reconstructions to dual energy computed tomography acquisitions was feasible and resulted in significantly higher image quality scores, interpretability, and diagnostic performance. PMID- 26351036 TI - The relationship of breast density in mammography and magnetic resonance imaging in high-risk women and women with breast cancer. AB - PURPOSE: To evaluate the relationship between mammographic breast density (MBD), background parenchymal enhancement (BPE), and fibroglandular tissue (FGT) in women with breast cancer (BC) and at high risk for developing BC. METHODS: Our institutional database was queried for patients who underwent mammography and MRI. RESULTS: Four hundred three (85%) had BC and 72 (15%) were at high risk. MBD (P=.0005), BPE (P<.0001), and FGT (P=.02) were all higher in high-risk women compared to the BC group. CONCLUSIONS: Higher levels of MBD, BPE and FGT are seen in women at higher risk for developing BC when compared to women with BC. PMID- 26351037 TI - Comparison between two assessment methods for exercise-induced laryngeal obstructions. AB - Exercise-induced laryngeal obstructions (E-ILOs) are important differential diagnoses to exercise-induced asthma and are diagnosed by the continuous laryngoscopy exercise (CLE) test. There are two different methods for evaluating the severity of E-ILOs using recordings from the CLE test; the CLE score and EILOMEA. The aim of this study was to investigate the consistency between these methods. Using their respective method, the developers of each method evaluated 60 laryngoscopic recordings from patients with different subtypes and various levels of severity of E-ILOs. The CLE score evaluates glottic and supraglottic obstructions on a 4-grade scale. EILOMEA uses software to calculate the obstruction severity on continuous scales from a still frame of the larynx during maximal obstruction giving three parameters reflecting glottic and supraglottic obstruction. The means of the EILOMEA measures differed significantly for CLE score 1 vs. 2 and 2 vs. 3, but not for 0 vs. 1 for glottic as well as supraglottic obstructions. The EILOMEA method does not distinguish between CLE score 0 and 1, but otherwise the methods correlate. Since previous studies have suggested that only CLE scores of 2 and 3 reflect a severity of E-ILOs of clinical importance, this lack of the EILOMEA method is not crucial for a correct medical evaluation. PMID- 26351038 TI - Lateral semicircular canal fistula in cholesteatoma: diagnosis and management. AB - The objective of this retrospective study was to present the authors' experience on the management of labyrinthine fistula secondary to cholesteatoma. 695 patients, who underwent tympanoplasty for cholesteatoma, in a University Hospital between 1993 and 2013 were reviewed, to select only those with labyrinthine fistulas. 42 patients (6%) had cholesteatoma complicated by fistula of the lateral semicircular canal (LSCC). The following data points were collected: symptoms, pre- and postoperative clinical signs, surgeon, CT scan diagnosis, fistula type, surgical technique, preoperative vestibular function and audiometric outcomes. Most frequent symptoms were unspecific, such as otorrhea, hearing loss and dizziness. However, preoperative high-resolution computed tomography predicted fistula in 88 %. Using the Dornhoffer and Milewski classification, 16 cases (38 %) were identified as stage 1, 22 (52 %) as stage II, and 4 (10 %) as stage III. The choice between open or closed surgical procedure was independent of the type of fistulae. The cholesteatoma matrix was completely removed from the fistula and immediately covered by autogenous material. In eight patients (19 %), the canal was drilled with a diamond burr before sealing with autologous tissue. After surgery, hearing was preserved or improved in 76 % of the patients. There was no statistically significant relationship between the extent of the labyrinthine fistula and the hearing outcome. In conclusion, a complete and nontraumatic removal of the matrix cholesteatoma over the fistula in a one-staged procedure and its sealing with bone dust and fascia temporalis, with sometimes exclusion of the LSCC, is a safe and effective procedure to treat labyrinthine fistula. PMID- 26351039 TI - Synthesis, alpha-glucosidase inhibitory and molecular docking studies of prenylated and geranylated flavones, isoflavones and chalcones. AB - Three series of prenylated and/or geranylated flavonoids were synthesized and evaluated for their alpha-glucosidase inhibitory activity. The 3',5' digeranylated chalcone (16) was identified as a new alpha-glucosidase inhibitor whose activity (IC50=0.90 MUM) was 50-fold more than that of acarbose (IC50=51.32 MUM). Molecular docking studies revealed the existence of strong hydrophobic interaction and H-bonding between compound 16 and alpha-glucosidase's active site. The inhibitory mode analysis showed that 16 exhibited a competitive inhibitory mode. PMID- 26351040 TI - In vitro COX-1 and COX-2 enzyme inhibitory activities of iridoids from Penstemon barbatus, Castilleja tenuiflora, Cresentia alata and Vitex mollis. AB - A group of sixteen iridoids isolated from plants used as anti-inflammatory remedies in Mexican folk medicine were evaluated for their potential to inhibit cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes. From these assays, loganic acid (10) was identified as the most promising compound with both COX-1 (36.0 +/- 0.6%) and COX-2 (80.8 +/- 4.0%) inhibition at 10 MUM. Compound 10 shows a better inhibition against the COX-2 enzyme. Other iridoids tested in the present study showed weak or no inhibition against these enzymes. Furthermore, herein are presented key interactions of iridoid 10 with COX-1 and COX-2 enzymes through molecular docking studies. These studies suggest that 10 exhibits anti inflammatory activity due to COX inhibition. PMID- 26351041 TI - Dual biological functions of the apoptotic activity and anti-inflammatory effect by alcyonolide congeners from the Okinawan soft coral, Cespitularia sp. AB - In our current study, alcyonolide and its congeners isolated from the Okinawan soft coral, Cespitularia sp., have shown an antitumor activity in HCT116 colon cancer cells. This study investigated the biological activities of these compounds (1-12) for the apoptotic activity in the HCT116 cells and the anti inflammatory effect in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. As a result, the apoptotic cells with a nuclear condensation were detected by treatment with these compounds. The apoptotic cells dependent on the caspase 3/7 activation was also induced in the low concentration range of 2.5-10 MUM. While a similar concentration of the compounds inhibited the NO production in the LPS stimulated inflammatory RAW264.7 cells, the pro-inflammatory gene expressions of the iNOS and COX-2 mRNA were also suppressed. The structurally unique alcyonolides (5, 12) having the dual biological activity of apoptotic activity and anti-inflammatory effect could be a potential development as pharmaceutical agents. PMID- 26351042 TI - Cytotoxic labdane-type diterpenes from Hedychium longipetalum inhibiting production of nitric oxide. AB - Three new labdane diterpenes, hedylongnoids A (1), B (2) and C (3), were isolated from the rhizomes of Hedychium longipetalum, together with three known ones yunnancoronarin A (4), hedyforrestin C (5) and hedyforrestin B (6). Their structures were established by spectroscopic analysis, including 2D-NMR spectroscopic techniques. Compounds 1-6 exhibited inhibitory effects against nitric oxide (NO) production in LPS and IFN-gamma-induced RAW 264.7 murine macrophages with IC50 values ranging from 0.56 to 7.50 MUg/ml, and 3-6 showed cytotoxicities against cancer cell lines SGC-7901 and Hela with IC50 values ranging from 6.21 to 14.53 MUg/ml and from 6.58 to 14.83 MUg/ml, respectively. PMID- 26351043 TI - Synthesis of fluorescent dipeptidomimetics and their ribosomal incorporation into green fluorescent protein. AB - The synthesis and incorporation into position 66 of green fluorescent protein (GFP) by in vitro protein translation of novel oxazole and thiazole based dipeptidomimetics are described. The compounds may be regarded as GFP chromophore analogues, and are strongly fluorescent. An alpha-amido-beta-ketoester intermediate was obtained via bisacylation of a protected glycine. The intermediate underwent dehydrative cyclization to afford the 1,3-oxazole and was treated with Lawesson's reagent to furnish the 1,3-thiazole. When these fluorophores were introduced into position 66 of GFP in place of Tyr66, the resulting GFP analogues exhibited fluorescence emission several-fold greater than wild-type GFP; the emission was also shifted to shorter wavelength. It may be noted that compared to the typical fluorophores formed in the natural and modified fluorescent proteins, the oxazole and thiazole fluorophores are completely stable and do not require activation by posttranslational modification to exhibit fluorescence. PMID- 26351044 TI - Trophic flexibility and opportunism in pike Esox lucius. AB - The first comprehensive investigation of pike Esox lucius trophic ecology in a region (Ireland) where they have long been thought to be a non-native species is presented. Diet was investigated across habitat types (lake, river and canal) through the combined methods of stable-isotope and stomach content analyses. Variations in niche size, specialization and the timing of the ontogenetic dietary switch were examined, revealing pronounced opportunism and feeding plasticity in E. lucius, along with a high occurrence of invertivory (up to 60 cm fork length, LF ) and a concomitant delayed switch to piscivory. Furthermore, E. lucius were found to primarily prey upon the highly available non-native roach Rutilus rutilus, which may alleviate predation pressure on brown trout Salmo trutta, highlighting the complexity of dynamic systems and the essential role of research in informing effective management. PMID- 26351045 TI - [Advances in genetic studies of Charcot-Marie-Tooth disease type 4 (CMT4)]. AB - The Charcot-Marie-Tooth disease (CMT) is one of the most common human inherited peripheral neuropathies. The most common pattern of inheritance is autosomal dominant, with less often occurrence autosomal recessive and X-linked dominant/recessive inheritance. CMT is generally divided into three forms: demyelinating forms (CMT1), axonal forms (CMT2) and intermediate forms (DI-CMT). The autosomal recessive form (AR-CMT1 or CMT4) is accompanied by progressive distal muscle weakness and atrophy of the limbs, pes cavus and claw-like hands. In addition, CMT4 is also characterized by early onset, rapid progression, and varying degrees of sensory loss and spinal deformities (e.g. scoliosis). Recently, 11 subtypes of CMT4 have been identified. Some of these subtypes were clear in pathogenic mechanisms, some had founder mutation, but some still had limited clinical description and mutation analysis. In this review, we summarize the latest research progresses of CMT4, including genotypes and phenotypes, pathogenic mechanisms and mouse models. PMID- 26351046 TI - [Pathogenic mechanism and therapies for Gaucher's disease]. AB - Gaucher's disease (GD) also named glucocerebroside lipidosis, is the most common kind of 1ysosomal storage disorder. It results from an autosomal recessive deficiency of the lysosomal enzyme acid beta-glucosidase/ beta-glucocerebrosidase (GBA), which is responsible for hydrolysis of glucocerebroside/glucosylceramide (GlcCer) into glucose and ceramide. Absent or reduced enzymatic activity of GBA leads to multisystemic accumulation of GlcCer in mononuclear phagocyte system and various tissues, such as brain, liver, spleen and so on, causing brain injury, liver splenomegaly, bone damage, the reduction of blood cells and individual growth retardation. GD type I could be treated by enzyme replacement therapy (ERT), but GD types II and III have not effective treatment. In this review, we summarize the recent progress on pathogenic mechanism and therapies in GD. PMID- 26351047 TI - [Progress of epigenetics and its therapeutic application in hepatocellular carcinoma]. AB - Liver cancer is a severe harmful disease. It is the fifth most frequently diagnosed cancer and second most frequent cause of cancer deaths worldwide. As the most popular histologic subtype of hepatocellular carcinoma (HCC), primary HCC is a heterogeneous disease whose management requires a multidisciplinary approach combining genetics, genomics and environmental toxicology. Although many molecular targeted therapies such as sorafenib have entered clinical application and proven effective, the cytotoxicity and other negative effects cannot be ignored. There is an urgent need to identify new therapeutic targets and drugs, which can kill HCC cells with high efficiency and specificity. Plenty of evidence suggests that occurrence and development of HCC is closely related with epigenetics. DNA methylation, histone modification, aberrant expression of miRNAs and dysregulated expression of many epigenetic regulatory genes are significantly altered in HCC. Epigenetic therapeutic drugs may reverse abnormal gene expression, thus controlling the occurrence and development of HCC. In this review, we summarize the latest research progresses in epigenetics and its therapeutic application in HCC,and the potential treatments to be used in the future. PMID- 26351048 TI - [The transcriptome research progresses of skin hair follicle development]. AB - Recently, transcriptome sequencing technology has achieved significant progresses in gene network regulation of important economic traits in animals. As the derivative of mammalian skin, hair follicle is capable of self-renew. Its proliferation and differentiation result in hair formation. Researches have revealed that many growth factors and receptors coordinate genes and environment, as well as play an extremely important role during hair growth. In this review, we summarize the progresses that transcriptome sequencing technologies have achieved in researches of hair follicle development and renegeration in a variety of species, such as humans, mice, goats. We aim to provide theoretical mechanisms for the artificial interference of villus growth cycle, and new ideas for therapeutic treatment of skin hair follicle- related diseases. PMID- 26351049 TI - [Occurrence characteristics and molecular genetic basis of pod shattering in soybean]. AB - Pod shattering is a natural property of wild soybean (Glycine soja) for propagation and also a major cause of yield loss in cultivated soybean (Glycine max L. Merr). Thus, studies on occurrence characteristics and molecular genetic basis of pod shattering in soybean can provide insights into both molecular mechanisms and potential application in legume crop improvement. In this review, we summarize the occurrence features and phenotypic identification methods of pod shattering based on analysis of the cellular microstructure of shattering resistant soybean pod. We also introduced the identification and breeding of shattering-resistant germplasms, the progress of molecular genetic studies on shattering-resistant phenotype in soybean as well as perspectives on future studies of pod-shattering trait and application in crop improvement. PMID- 26351050 TI - [Advances in lineage-specific genes]. AB - Lineage-specific genes (LSGs) are defined as genes found in one particular taxonomic group but have no significant sequence similarity with genes from other lineages, which compose about 10%?20% of the total genes in the genome of a focal organism. LSGs were first uncovered in the yeast genome in 1996. The development of the whole genome sequencing leads to the emergence of studies on LSGs as a hot topic in comparative genomics. LSGs have been extensively studied on microbial species, lower marine organisms, plant (such as Arabidopsis thaliana, Oryza sativa, Populus), insects, primate, etc; the biological functions of LSGs are important to clarify the evolution and adaptability of a species. In this review, we summarize the progress of LSGs studies, including LSGs identification, gene characterization, origin and evolution of LSGs, biological function, and expression analysis of LSGs. In addition, we discuss the existing problems and future directions for studies in this area. Our purpose is to provide some unique insights into the researches of LSGs. PMID- 26351051 TI - [Role of miRNA in plant seed development]. AB - MicroRNA (miRNA), a class of non-coding small RNAs, has been reported to be involved in a broad range of metabolic and physiological processes in plants, such as plant growth, development and responses to stresses. They participate in gene expression by degrading target genes at post-transcriptional levels. Seeds are the basic elements of plant growth and important materials for agriculture. miRNAs have been identified to be involved in seed development in many plants. Herein we review recent progresses on the miRNAs involved in seed development and their regulatory mechanisms, which will help to provide insights into further research to improve seed quality. PMID- 26351052 TI - [A gain-of-function mutation in FGFR2 influences mandibular condylar development on mice]. AB - The development of the skeleton is regulated by numerous signaling molecules expressed in epiphyseal cartilage controlling both chondrogenesis and osteogenesis such as fibroblast growth factor receptors (FGFRs). In order to explore the important effect of fibroblast growth factor receptor 2 (FGFR2) in the process of mandibular condylar growth, we introduced gain-of-function Fgfr2(+/S252W) mice, and investigated mandibular condylar morphology by means of safranin-o/fast green staining at the stage of 1 week, 3 weeks and 6 weeks. The mutant mice displayed narrower width of the mandibular condylar growth plate, stronger stainings of trabecular bone at the stage of 1 week, 3 weeks and 6 weeks and faster degradation of the calcified cartilage cell layer at the stage of 6 weeks. We also assessed the expression of type X collagen (Col X) in mandibular condyle at the stage of 3 weeks by immunohistochemical staining and real-time PCR. The results showed that Col X was increased in the mutant mice. In conclusion, the gain-of-function mutation in FGFR2 resulted in histopathological abnormalities and development deformity of mandibular condyle cartilage in mice, which inhibited endochondral bone formation. PMID- 26351053 TI - [Re-sequencing and assembly of chicken T cell receptor gamma locus]. AB - The genomic organization of the animal T cell receptor (TCR) loci is characterized by different gene families with high homology, and it is quite difficult to obtain accurate gene sequences and arrangements of these gene families. In this study, we identified the location of chicken TCR gamma chain (TCRgamma or TRG) genes by comparing those TRG gene sequences with the chicken reference genome, and the corresponding bacterial artificial chromosome (BAC) clone, CH261-174P24, was chosen for further high-throughput DNA re-sequencing and assembly. As a result, a draft genome assembly containing ten scaffolds was obtained, which almost covered the chicken TRG gene locus and the flanking regions. Subsequently, the internal structure of these scaffolds was confirmed by PCR amplification and Sanger sequencing. Our analysis corrected two errors in the sequence-one near a TRG variable gene and one close to a gap, respectively, and several errors in the TRG variable genes in the chicken reference genome. In conclusion, our work has partially corrected the erroneously assembled sequences of the TRG gene locus in the chicken reference genome and thus provides a new method for genome sequence analysis of chicken TRA/D and TRB gene loci. PMID- 26351054 TI - [The effects of transgenic Cry1Ac+Cry2Ab cotton on cotton bollworm control and functional response of predators on whitefly]. AB - In this study, we detected and clarified the roles of transgenic Cry1Ac+Cry2Ab cotton "639020" in controlling cotton bollworm (Helicoverpa armigera) during critical periods of bud stage (second generation of bollworm), flowering stage (third generation of bollworm) and bolling stage (fourth generation of bollworm) as well as the influences of 639020 cotton on functional response of the main predators (Chrysopa sinica larvae, Propylaea japonica, Orius and Erigonidium graminicola ) on whitefly using transgenic Cry1Ac cotton "CCRI41" and conventional cotton "CCRI49" as the control. Our results showed that the 639020 cotton well controlled the second and third generation of bollworm, and the level of insect resistance increased by 52.85% and 16.22% separately compared with that of CCRI41, with a significant effect on the second generation of bollworm. Moreover, the number of bollworm eggs in 639020 cotton field was lower than that in CCRI41 and CCRI49 cotton fields (except the second generation of bollworm) during the cotton bud, flowering and bolling stages. Although the number of bollworm larvae in 639020 cotton field was significantly lower than that in CCRI49 field, and both under the controlling index, it has no significant difference compared with that in CCRI41 cotton field. There were also no obvious changes in predator functions of Chrysopa sinica, Propylaea japonica, Orius and Erigonidium graminicola on bemisia tabaci between 639020, CCRI41 and CCRI49 cotton filed. This study evaluated the safety of new transgenic cotton on environment, anti-insect activity of exogenous gene and the safety of production and application prospect. PMID- 26351055 TI - [Genetic analysis and identification of candidate genes for a narrow leaf mutant (zy17) in rice]. AB - Control of organ size by cell proliferation and cell expansion is a fundamental process in plant development, but little is known about the genetic and molecular mechanisms that determine organ size in plants. To understand the genetic and molecular mechanisms of organ growth control, we isolate a set of mutants with altered leaf size and identify the narrow leaf mutant, zhaiye 17 (zy17) (zhaiye means narrow leaf in Chinese). zy17 exhibits narrow leaves, slightly short plants, small panicles, reduced panicle branches and decreased grain numbers per panicle compared with the wild type. Our cytological analyses show that the narrow leaf phenotype of zy17 is caused by the reduced number of cells, indicating that ZY17 regulates cell proliferation. Genetic analyses show that the zy17 mutant phenotypes are controlled by a single gene. Using the whole genome resequencing approach and linkage analysis, we identify Os02g22390, Os02g28280 and Os02g29530 as candidate genes. Os02g22390 encodes a retrotransposon protein with the mutation occurring in the intronic region; Os02g28280 encodes a protein with unknown function with a base substitution resulting in non-synonymous mutation; Os02g29530 encodes a protein containing the PFAM domain related to glycosyltransferase, with a 2 bp deletion mutation causing a premature termination. Further studies on these three candidate genes will be helpful for understanding the molecular mechanism of organ size control in rice. PMID- 26351056 TI - [Identification of the 1RS-7DS.7DL wheat-rye small segment translocation lines]. AB - Rye (Secale cereale L., RR) is a valuable genetic resource for the improvement of common wheat (Triticum aestivum L., AABBDD). Transferring alien rye genes into wheat by distant hybridization and automatic chromosome doubling is an important and efficient method to boost agronomic traits, disease resistance and widening the gene pool in wheat. In this study, an octoploid triticale CD-13 (AABBDDRR) was obtained via automatic chromosome doubling by crossing landrace Penganbaimaizi (T. aestivum L., AABBDD) and rye "Qinling rye" (S. cereale cv. Qinling, RR). GISH and FISH analyses indicated that CD-13 contained a 1RS-7DS.7DL wheat-rye small segment translocation chromosome. In order to transfer the 1RS 7DS small segment translocation into hexaploid wheat, 58 lines of the F5 inbred population from the cross CD-13 x Chuanmai 42 were screened for rye chromosome segments by GISH and FISH analyses. The results showed that 13 lines contained the 1RS-7DS.7DL small segment translocation chromosome by reciprocal translocation between 1RS and 7DS. These translocation lines carrying 1RS small rye alien segment were tested for the translocation breakpoints and the presence of a storage protein locus Sec-1. The Sec-1 locus was absent in the line 811, a stable 1RS-7DS.7DL small segment translocation line. The translocation breakpoint of 1RS-7DS.7DL of this line was located in the interval of IB267-IAG95 around the telomere of 1RS chromosome. Thousand-kernel weight of the line 811 was much higher than the parent CD-13, but not significantly different from Chuanmai 42. This indicated that 1RS-7DS.7DL small segment translocation had no negative effect on thousand-kernel weight in the genetic background of Chuanmai 42. The line with 1RS-7DS.7DL translocation chromosomes can be used as a new genetic material for further studies of valuable genes and their genetic effect on 1RS small segment. PMID- 26351057 TI - [Improvement of genetics teaching using literature-based learning model]. AB - Genetics is one of the most important courses for undergraduate students majoring in life science. In recent years, new knowledge and technologies are continually updated with deeper understanding of life science. However, the teaching model of genetics is still based on theoretical instruction, which makes the abstract principles hard to understand by students and directly affects the teaching effect. Thus, exploring a new teaching model is necessary. We have carried out a new teaching model, literature-based learning, in the course on Microbial Genetics for undergraduate students majoring in biotechnology since 2010. Here we comprehensively analyzed the implementation and application value of this model including pre-course knowledge, how to choose professional literature, how to organize teaching process and the significance of developing this new teaching model for students and teachers. Our literature-based learning model reflects the combination of "cutting-edge" and "classic" and makes book knowledge easy to understand, which improves students' learning effect, stimulates their interests, expands their perspectives and develops their ability. This practice provides novel insight into exploring new teaching model of genetics and cultivating medical talents capable of doing both basic and clinical research in the "precision medicine" era. PMID- 26351058 TI - [Advances in understanding Drosophila salivary gland polytene chromosome and its applications in genetics teaching]. AB - Drosophila salivary gland polytene chromosome, one of the three classical chromosomes with remarkable characteristics, has been used as an outstanding model for a variety of genetic studies since 1934. The greatest contribution of this model to genetics has been providing extraordinary angle of view in studying interphase chromosome structure and gene expression regulation. Additionally, it has been extensively used to understand some special genetic phenomena, such as dosage compensation and position-effect variegation. In this paper, we briefly review the advances in the study of Drosophila salivary gland chromosome, and try to systematically and effectively introduce this model system into genetics teaching practice in order to steer and inspire students' interest in genetics. PMID- 26351059 TI - Laparoscopic ventral rectopexy is the gold standard treatment for rectal prolapse. PMID- 26351060 TI - Effects of exogenous melatonin and photoperiod on sexual maturation in pullets. AB - Hy-Line Gray commercial pullets were maintained under 8-h photoperiods, 16-h photoperiods and 16-h photoperiods supplemented with a diet containing 20 or 200 mg/kg melatonin (MEL) to investigate the role of MEL in sexual development. A total of 256 Hy-Line Gray commercial pullets were placed, four birds to a cage, in four similar light-proof rooms (8-h photoperiod) at 6 weeks of age. At 70 day, three rooms containing a total of 192 birds were transferred to a 16-h photoperiod, whereas 64 birds were maintained under the 8-h photoperiod. Diets containing MEL at 20 and 200 mg/kg were fed to birds in two of the rooms under 16 h photoperiods. Birds maintained under an 8-h photoperiod matured 11.25 day later than those maintained under a 16-h photoperiod (p < 0.05). The group of birds receiving 20 mg/kg MEL matured 1.19 day later than those maintained under the 16 h photoperiod and 10.06 day earlier than those maintained under the 8-h photoperiod. The group of birds receiving 200 mg/kg MEL matured 3.13 day later than those maintained under a 16-h photoperiod and 8.12 day earlier than those maintained under an 8-h photoperiod. The average body weight of birds maintained under the 8-h photoperiod was greater than that of birds maintained under the 16 h photoperiod (p < 0.05) and was similar between the different MEL groups. The abdominal fat weight was lower in 16L:8D group compared with 8L:16D group (p < 0.05). The concentrations of follicle-stimulating hormone, luteinizing hormone, oestrogen and insulin did not differ significantly among the groups. The melatonin concentration in 200 mg/kg melatonin group was higher than that observed in the other groups; however, this concentration did not differ significantly (p > 0.05). These data suggest that the birds did not perceive the final 8-h photoperiod as being part of the night when they were given the MEL diets; continuously high plasma MEL was not observed in birds that responded as if they were in constant darkness. However, the later maturity of the groups administered MEL diets compared with the groups maintained under a constant 16-h photoperiod clearly indicated that MEL has some influence on the sexual maturity of pullets. PMID- 26351061 TI - Morphological characteristics of cultured fresh and thawed pericardium cells. AB - The need for selection of the optimal material for the manufacturing of cardio patches can be resolved by the use of cryostored autologous pericardial tissue. This short communication is a concise fragment of a large-scale research and demonstrates only the efficiency of cell culturing before and after pericardial preservation in the low temperature conditions. PMID- 26351062 TI - Time, space and form: Necessary for causation in health, disease and intervention? AB - Sir Austin Bradford Hill's 'aspects of causation' represent some of the most influential thoughts on the subject of proximate causation in health and disease. Hill compiled a list of features that, when present and known, indicate an increasing likelihood that exposure to a factor causes-or contributes to the causation of-a disease. The items of Hill's list were not labelled 'criteria', as this would have inferred every item being necessary for causation. Hence, criteria that are necessary for causation in health, disease and intervention processes, whether known, knowable, or not, remain undetermined and deserve exploration. To move beyond this position, this paper aims to explore factors that are necessary in the constitution of causative relationships between health, disease processes, and intervention. To this end, disease is viewed as a causative pathway through the often overlapping stages of aetiology, pathology and patho-physiology. Intervention is viewed as a second, independent causative pathway, capable of causing changes in health for benefit or harm. For the natural course of a disease pathway to change, we argue that intervention must not only occupy the same time and space, but must also share a common form; the point at which the two pathways converge and interact. This improved conceptualisation may be used to facilitate the interpretation of clinical observations and inform future research, particularly enabling predictions of the mechanistic relationship between health, disease and intervention. PMID- 26351063 TI - On balance: weighing harms and benefits in fundamental neurological research using nonhuman primates. AB - One of the most controversial areas of animal research is the use of nonhuman primates for fundamental research. At the centre of the controversy is the question of whether the benefits of research outweigh the harms. We argue that the evaluation of harms and benefits is highly problematic. We describe some common procedures in neurological research using nonhuman primates and the difficulties in evaluating the harm involved. Even if the harm could be quantified, it is unlikely that it could be meaningfully aggregated over different procedures, let alone different animals. A similar problem arises for evaluating benefits. It is not clear how benefits could be quantified, and even if they could be, values for different aspects of expected benefits cannot be simply added up. Sorting harms and benefits in three or four categories cannot avoid the charge of arbitrariness and runs the risk of imposing its structure on the moral decision. The metaphor of weighing or balancing harms and benefits is inappropriate for the moral decision about whether to use nonhuman primates for research. Arguing that the harms and benefits in this context are incommensurable, we suggest describing the moral consideration of harms and benefits as a coherent trade-off. Such a decision does not require commensurability. It must be well-informed about the suffering involved and the potential benefits, it must be consistent with the legal, regulatory and institutional framework within which it is made, and it must cohere with other judgments in relevant areas. PMID- 26351064 TI - Botulinum toxin A injection of UES in schizencephaly with dysphagia: Case report. AB - A 4-year-old schizencephaly patient admitted to authors' institution with dysphagia caused by upper esophageal sphincter (UES) dysfunction. Videofluoroscopic swallowing study (VFSS) was done for the diagnosis and the botulinum toxin type A (BTX-A) was injected to the cricopharyngeal muscle. UES dysfunction improved and oral feeding was possible after the injection. This normal swallowing function remained for over 79 months which was confirmed by follow up VFSS. To the best of our knowledge, this is first case of schizencephaly patient to be treated by BTX-A for UES dysfunction and longest to maintain its effect with single session of injection. PMID- 26351065 TI - Valsalva manoeuvre: A confusing dichotomatic misnomer. AB - OBJECTIVES: The aim of this study is to try to understand the origin of the definition of the Valsalva manoeuvre by going back to original documents and finding out at which moment, the eponym was given to these two different manoeuvres, and their congruence to reality. METHODS: Historical study of selected textbooks and articles about the Valsalva manoeuvre. RESULTS: Valsalva effectively described the manoeuvre against closed nostrils and mouth at the beginning of the 18th century, but he was not the first. On the contrary, Valsalva did not describe the manoeuvre against a closed glottis. This was a mid 20th century creation. CONCLUSIONS: Two questions remain: 1. What should be done with the eponymous appellation of the manoeuvre with closed mouth and nostrils? Certainly to keep it, even if Valsalva was not the first to clearly describe it. 2. What to do with the eponymous appellation of the manoeuvre with a closed glottis? It would be ideal to change it, as it is misnamed, confusing, and only recently formulated. PMID- 26351066 TI - Theoretical Explanation for How SO3H-Functionalized Ionic Liquids Promote the Conversion of Cellulose to Glucose. AB - While the catalytic transformation of cellulose to glucose by functionalized ionic liquids (ILs) has been achieved successfully under mild conditions, insight into the fundamental molecular mechanism is still lacking. The present work presents the first attempt to address the fundamental reaction chemistry of the catalytic transformation. An enzyme-like catalytic mechanism of ILs, in which glycosidic bond hydrolysis proceeds through a retaining mechanism and/or an inverting mechanism, is proposed. DFT calculations show that both mechanisms involve moderate barriers (<30 kcal mol(-1)), which is consistent with the catalytic performance of the ILs under mild conditions (<100 degrees C). The "biomimetic" mechanism model proposed herein is expected to be viable for understanding the unique catalytic activity of ILs under mild conditions. PMID- 26351067 TI - Expression of the hyaluronan-mediated motility receptor RHAMM in tumor budding cells identifies aggressive colorectal cancers. AB - Expression of the hyaluronan-mediated motility receptor (RHAMM, CD168) predicts adverse clinicopathological features and decreased survival for colorectal cancer (CRC) patients. Using full tissue sections, we investigated the expression of RHAMM in tumor budding cells of 103 primary CRCs to characterize the biological processes driving single-cell invasion and early metastatic dissemination. RHAMM expression in tumor buds was analyzed with clinicopathological data, molecular features and survival. Tumor budding cells at the invasive front of CRC expressed RHAMM in 68% of cases. Detection of RHAMM-positive tumor budding cells was significantly associated with poor survival outcome (P = .0312), independent of TNM stage and adjuvant therapy in multivariate analysis (P = .0201). RHAMM positive tumor buds were associated with frequent lymphatic invasion (P = .0007), higher tumor grade (P = .0296), and nodal metastasis (P = .0364). Importantly, the prognostic impact of RHAMM expression in tumor buds was maintained independently of the number of tumor buds found in an individual case (P = .0246). No impact of KRAS/BRAF mutation, mismatch repair deficiency and CpG island methylation was observed. RHAMM expression identifies an aggressive subpopulation of tumor budding cells and is an independent adverse prognostic factor for CRC patients. These data support ongoing efforts to develop RHAMM as a target for precision therapy. PMID- 26351068 TI - CO2 emissions, real output, energy consumption, trade, urbanization and financial development: testing the EKC hypothesis for the USA. AB - This study aims to investigate the relationship between carbon dioxide (CO2) emissions, energy consumption, real output (GDP), the square of real output (GDP(2)), trade openness, urbanization, and financial development in the USA for the period 1960-2010. The bounds testing for cointegration indicates that the analyzed variables are cointegrated. In the long run, energy consumption and urbanization increase environmental degradation while financial development has no effect on it, and trade leads to environmental improvements. In addition, this study does not support the validity of the environmental Kuznets curve (EKC) hypothesis for the USA because real output leads to environmental improvements while GDP(2) increases the levels of gas emissions. The results from the Granger causality test show that there is bidirectional causality between CO2 and GDP, CO2 and energy consumption, CO2 and urbanization, GDP and urbanization, and GDP and trade openness while no causality is determined between CO2 and trade openness, and gas emissions and financial development. In addition, we have enough evidence to support one-way causality running from GDP to energy consumption, from financial development to output, and from urbanization to financial development. In light of the long-run estimates and the Granger causality analysis, the US government should take into account the importance of trade openness, urbanization, and financial development in controlling for the levels of GDP and pollution. Moreover, it should be noted that the development of efficient energy policies likely contributes to lower CO2 emissions without harming real output. PMID- 26351069 TI - Coencapsulation of Target Effector Cells With Mesenchymal Stem Cells Reduces Pericapsular Fibrosis and Improves Graft Survival in a Xenotransplanted Animal Model. AB - Pericapsular fibrotic overgrowth (PFO) is a problem that thwarts full implementation of cellular replacement therapies involving encapsulation in an immunoprotective material, such as for the treatment of diabetes. Mesenchymal stem cells (MSCs) have inherent anti-inflammatory properties. We postulated that coencapsulation of MSCs with the target cells would reduce PFO. A hepatoinsulinoma cell line (HUH7) was used to model human target cells and was coencapsulated with either human or mouse MSCs at different ratios in alginate microcapsules. Viability of encapsulated cells was assessed in vitro and xenografted either intraperitoneally or subcutaneously into C57BL/6 mice. Graft retrieval was performed at 3 weeks posttransplantation and assessed for PFO. Coencapsulation of human MSCs (hMSCs) or mouse MSCs (mMSCs) with HUH7 at different ratios did not alter cell viability in vitro. In vivo data from intraperitoneal infusions showed that PFO for HUH7 cells coencapsulated with hMSCs and mMSCs in a ratio of 1:1 was significantly reduced by ~30% and ~35%, respectively, compared to HUH7 encapsulated alone. PFO for HUH7 cells was reduced by ~51% when the ratio of mMSC/HUH7 was increased to 2:1. Implanting the microcapsules subcutaneously rather than intraperitoneally substantially reduced PFO in all treatment groups, which was most significant in the mMSC/HUH7 2:1 group with a ~53% reduction in PFO compared with HUH7 alone. Despite the reduced PFO reaction to the individual microcapsules implanted subcutaneously, all microcapsule treatment groups were contained in a vascularized fibrotic pouch at 3 weeks. The presence of MSCs in microcapsules retrieved from these fibrotic pouches improved graft survival with significantly higher cell viabilities of 83.1 +/- 0.6% and 79.1 +/- 0.8% seen with microcapsules containing mMSC/HUH7 at 2:1 and 1:1 ratios, respectively, compared to HUH7 alone (51.5 +/- 0.7%) transplanted subcutaneously. This study showed that coencapsulation of MSCs with target cells has a dose-dependent effect on reducing PFO and improving graft survival when implanted either intraperitoneally or subcutaneously in a stringent xenotransplantation setting. PMID- 26351070 TI - Modern methods for vancomycin determination in biological fluids by methods based on high-performance liquid chromatography--A review. AB - Vancomycin is a glycopeptide antibiotic used in the therapy of severe bacterial infection. The monitoring of vancomycin levels is recommended because of its narrow therapeutic index and toxicity. This measurement is especially appropriate in patients with unstable renal functions, who receive high doses of vancomycin or present serious bacterial infections accompanied by important sequestration of liquids when it could be difficult to achieve the optimal therapeutic dose. Most of the methods for vancomycin determination in routine practice are immunoassays. However, chromatography-based techniques in combination with UV or mass spectrometry detection provide results with greater accuracy and precision also in complicated biological matrices. This review provides a detailed overview of modern approaches for the chromatographic separation of vancomycin in various biological samples and useful sample preparation procedures for vancomycin determination in various biological fluids. PMID- 26351071 TI - The necessity of long-term follow-up including spinal examination after successful initial treatment of intracranial germinoma: case reports. AB - INTRODUCTION: Intracranial germinomas seldom recur at spinal space following whole-brain or whole-ventricular (WV) radiotherapy. The majority of the spinal recurrence takes place within 5 years after treatment; therefore, late spinal failure beyond 5 years after successful initial treatment is rare. CASE PRESENTATIONS: We describe the cases of two patients with intracranial germinoma, who developed spinal recurrence 7 and 9 years after the initial treatment with WV radiotherapy combined with and without chemotherapy, respectively. In both cases, spinal recurrent tumors were histologically diagnosed as germinoma and they were successfully treated with chemotherapy and local radiotherapy without tumor recurrence for 11 years and 11 months, respectively. CONCLUSION: Intracranial germinomas may potentially present with spinal recurrence many years after successful initial WV radiotherapy. Physicians must be aware of patients' symptoms during the clinical examination. Regular long-term monitoring, including spinal examination, is necessary for 5-10 years or longer. PMID- 26351072 TI - Audiological evaluation in children affected by myelomeningocele. AB - PURPOSE: The aim of the present study is to evaluate the auditory system in children affected by myelomeningocele and comparing the results with clinical neurological conditions. MATERIALS AND METHODS: Forty-three children, aged between 7 and 26 years, affected by myelomeningocele were investigated by means of subjective tonal audiometry and objective impedance audiometry (tympanometry and acoustic stapedial reflex). RESULTS: Audiological evaluation showed an alteration in 32 patients (74%%). Nine patients presented a mild hearing loss: bilateral in six cases (three sensorineural, one mixed, and two conductive) and unilateral in three cases (two mixed and one conductive). One patient had moderate unilateral conductive deafness and, finally another one severe unilateral sensorineural. Almost all patients with deafness were affected by myelomeningocele and Chiari II. Stapedial-cochlear reflex investigation showed an alteration in 30 patients (70%): 9 of these also showed deafness while the remaining 21 was normal hearing. In these 30 patients, we demonstrated the presence of myelomeningocele, hydrocephalus, and Chiari II malformation in 21 subjects (70%). CONCLUSION: Otoneurological evaluation is important in myelomeningocele not only at the birth but also in the follow-up. It could have an important prognostic role for neurological impairment. PMID- 26351073 TI - Minimizing blood transfusions in the surgical correction of craniosynostosis: a 10-year single-center experience. AB - INTRODUCTION: Our center previously reported low transfusion rates for craniosynostosis surgery by two experienced neurosurgeons using standard intraoperative techniques and acceptance of low hemoglobin levels. This study evaluated whether low rates were maintained over the last 10 years and if a less experienced neurosurgeon, trained in and practicing in the same environment, could achieve similar outcomes. METHODS: All craniosynostosis operations performed in children between 2004 and 2015 were reviewed retrospectively. Transfusion rates were calculated. Analyses examined the relationship of transfusion to craniosynostosis type, surgical procedure, redo operation, surgeon, and perioperative hemoglobin levels. RESULTS: Two hundred eighteen patients were included: 71 open sagittal, 28 endoscopic-assisted sagittal, 32 unicoronal, 14 bicoronal, 42 metopic, and 31 multisuture. Median age at operation was 9.1 months. Overall transfusion rate was 24 %: 17 % open sagittal, 7 % endoscopic-assisted sagittal, 6 % unicoronal, 21 % bicoronal, 45 % metopic, and 45 % multisuture. The timing of transfusions were 75, 21, and 4 % for intraoperative, postoperative, and both, respectively. Patients not receiving transfusion had a mean lowest hemoglobin of 87 g/l (range 61-111) intraoperatively and 83 g/l (range 58-115) postoperatively. Mean lowest hemoglobin values were significantly lower in those necessitating intraoperative (75 g/l, range 54-102) or postoperative (59 g/l, range 51-71) transfusions. There was no significant difference in transfusion rate between less and more experienced surgeons. There were no cardiovascular complications or mortalities. CONCLUSION: In craniosynostosis surgery, reproducible, long-term low blood transfusion rates were able to be maintained at a single center by careful intraoperative technique and acceptance of low intraoperative and postoperative hemoglobin levels in hemodynamically stable patients. Furthermore, low rates were also achieved by an inexperienced neurosurgeon in the group. This suggests that these results may be achievable by other neurosurgeons, who follow a similar protocol. PMID- 26351075 TI - Transumbilical arterial embolization of a large dural arteriovenous fistula in a low-birth-weight neonate with congestive heart failure. AB - PURPOSE: The purpose of this study was to report transumbilical arterial embolization of a large dural arteriovenous fistula (AVF) in a low-birth-weight neonate with congestive heart failure (CHF). CASE PRESENTATION: A female neonate was delivered by cesarean section at 31 weeks of gestation. Her birth weight was 1538 g and Apgar scores were 6 at both 1 and 5 min. Because of dyspnea and retracted respiration immediately after birth, she required mechanical ventilation. Ultrasound revealed right cardiac overload and a large cystic mass at the posterior brain. Magnetic resonance imaging on day 1 showed a large dural AVF (dural sinus malformation with arteriovenous (AV) shunts) at the torcular herophili. Umbilical artery and vein catheterization were performed on the same day for neurointervention. CHF prompted emergency embolization on day 8. The transfemoral arterial route could not be used because of its small size and compromised femoral artery blood flow. Transumbilical arterial embolization shrank the AV shunts markedly, resulting in clinical improvement, thus requiring no further intervention. Follow-up angiography at 4 months confirmed no residual AVF. Her growth and development were normal at the last follow-up at age 4 years. CONCLUSION: This patient apparently was the lowest birth weight neonate with a large AVF successfully treated by embolization, which is usually performed through the transfemoral arterial route. The transumbilical arterial route is an alternative for neonates with birth weight <2000 g and very small femoral arteries. PMID- 26351074 TI - CSF flow pathways through the ventricle-cistern interfaces in kaolin-induced hydrocephalus rats-laboratory investigation. AB - PURPOSE: The goal of this study was to identify direct cerebrospinal fluid (CSF) pathways in the interface between ventricles and cisterns. Such routes are hypothesized to be involved in alternative CSF flows in abnormal circumstances of CSF circulation. METHODS: Chronic obstructive hydrocephalus models were induced in ten Sprague-Dawley rats with kaolin injection into the cisterna magna. Three weeks after the kaolin injection, when thick arachnoid fibrosis obliterated the fourth ventricular outlets, cationized ferritin was stereotactically infused as a tracer into the lateral ventricle in order to observe the pathways from the ventricles to the subarachnoid space. Animals were killed in 48 h and brains were sectioned. CSF flow pathways were traced by the staining of ferritin with ferrocyanide. RESULTS: Eight out of ten rats developed hydrocephalus. The subarachnoid membranes of the convexity and basal cisterns were severely adhered such that most of the ferritin remained in the ventricles whereas basal and convexity cisterns were clear of ferritin. In six out of the eight hydrocephalus rats, ferritin leaked from the third ventricle into the quadrigeminal cistern, and from the lateral ventricle into the ambient cistern. CONCLUSIONS: The interfaces between the third ventricle and the quadrigeminal cistern, and between the lateral ventricle and the ambient cistern appear to be alternative CSF pathways in a pathologic condition such as obstructive hydrocephalus. PMID- 26351076 TI - STAT1 modification improves therapeutic effects of interferons on lung cancer cells. AB - BACKGROUND: Interferons (IFNs) have potent anti-proliferative, pro-apoptotic, and immunomodulatory activities against cancer. However, the clinical utility of IFNs is limited by toxicity and pharmacokinetics making it difficult to achieve sustained therapeutic levels especially in solid tumors. METHODS: Signal Transducer and Activator of Transcription 1 (STAT1) or a modified STAT1 (designated STAT1-CC) that is hyper-responsive to IFN were overexpressed in lung cancer SPC-A-1 and H1299 cells using lentiviral vectors. Transduction efficiency was monitored using enhanced green fluorescent protein (EGFP) expression. After transduction, cells were treated with interferon-gamma (IFN-gamma) or interferon beta (IFN-beta) and monitored for cell proliferation, migration, and invasiveness using Cell Counting Kit-8 and transwell chamber assays and for apoptosis using Annexin V detection by flow cytometry. In addition, levels of STAT1, STAT1 Tyr 701 phosphorylation (pSTAT1), fibronectin, and beta-catenin were determined using western blotting. In the case of IFN-gamma stimulation, levels of S100A4, proliferating cell nuclear antigen (PCNA), and c-fos expression were also determined. RESULTS: We found that expression of STAT1 or STAT1-CC enhanced the effect of IFN-gamma and, IFN-beta on inhibition of human lung cancer cell proliferation, migration and invasiveness. Moreover, STAT1 and STAT1-CC expression caused increases in pSTAT1 and decreases in fibronectin and beta catenin levels. STAT1-CC showed increased effects compared to STAT1 on IFN-gamma induced pSTAT1 and down-regulation of S100A4, PCNA, and c-fos levels. CONCLUSION: The results show that STAT1-CC exhibited more strength in improving the antitumor response of IFNs in lung cancer cells. Results from this study suggest that combined treatment of IFNs and STAT1-CC might be a feasible approach for the clinical management of lung cancer in the future. PMID- 26351079 TI - Microwave Assisted Synthesis, Physicochemical, Photophysical, Single Crystal X ray and DFT Studies of Novel Push-Pull Chromophores. AB - Two push-pull chromophores were synthesized by knoevenagel condensation under microwave irradiation. The structure of synthesized chromophores were established by spectroscopic (FT-IR, (1)H NMR, (13)C NMR, EI-MS) and elemental analysis. Structure of the chromophores was further conformed by X-ray crystallographic. UV Vis and fluorescence spectroscopy measurements provided that chromophores were good absorbent and fluorescent properties. Fluorescence polarity studies demonstrated that chromophores were sensitive to the polarity of the microenvironment provided by different solvents. Physicochemical parameters, including singlet absorption, extinction coefficient, stokes shift, oscillator strength, dipole moment and flurescence quantum yield were investigated in order to explore the analytical potential of the synthesized chromophores. In addition, the total energy, frontier molecular orbitals, hardness, electron affinity, ionization energy, electrostatic potential map were also studied computationally by using density functional theoretical method. PMID- 26351078 TI - Association of Telomerase Reverse Transcriptase Promoter Mutations with the Prognosis of Glioma Patients: a Meta-Analysis. AB - Previous studies have found that telomerase reverse transcriptase (TERT) has vital roles in the development of malignant diseases including glioma. The occurrence of TERT promoter mutations in gliomas is frequent. So far, several studies on the association between TERT promoter mutations and prognosis of gliomas had been published, but the conclusion was still not uncertain. The aim of the present meta-analysis was to assess the association between TERT promoter mutations and survival of glioma patients by pooling data from published studies. PubMed, Embase, and Web of Science were searched for articles on the association between TERT promoter mutations and survival of glioma patients until June 30, 2015. Hazard ratios (HR) and the 95% confidence intervals (CIs) were utilized to analyze the prognosis of glioma patients with TERT promoter mutations. Heterogeneity of included studies was assessed using Cochrane's Q test and I (2) method. Eleven studies with a total of 3,444 glioma patients were finally included into the meta-analysis. Nine studies reported the HRs adjusting for other confounding factors. Meta-analysis of total 11 studies suggested that TERT promoter mutations were significantly associated with worse prognosis of patients with gliomas (HR = 2.07, 95% CI = 1.58-2.71, P < 0.00001). Meta-analysis of nine studies with adjusted outcomes suggested that TERT promoter mutations were independently associated with worse prognosis of patients with gliomas (HR = 2.28, 95% CI = 1.72-3.01, P < 0.00001). In conclusion, TERT promoter mutation is a promising biomarker for predicting worse prognosis for patients with gliomas. More prospective well-designed cohort studies are needed to further validate its prognostic role in gliomas. PMID- 26351081 TI - ESTES News 5.2015. PMID- 26351080 TI - Cemented hip hemiarthroplasty clinical observations on unstable intertrochanteric fracture in elderlies. AB - OBJECTIVE: To observe the clinical effect of steel cable or greater trochanter reattachment (GTR) device combined with cemented hip hemiarthroplasty for unstable intertrochanteric fracture in elderlies. MATERIALS AND METHODS: From July 2002 to June 2014, a total of 57 elderly patients with unstable intertrochanteric fracture, including 23 males and 34 females, were treated. Their ages ranged from 80 to 95 years, with the average of 83 years. According to Evans-Jensen classification, there were 18 type IIa cases, 13 type IIb cases and 26 type III cases. All patients received cemented bipolar femoral head replacement, using steel cable or GTR device to stabilize the unstable intertrochanteric fracture. RESULTS: All patients had successful operation procedure and were followed up for 36 months. Postoperative X-ray revealed satisfying postoperative position of artificial hip joint, without subsidence or loosening. Three cases with the use of steel cable alone to treat greater trochanter fracture suffered from rupture of steel cable. The patients using GTR device showed good reduction at the site of displaced greater trochanter fracture and a firm fixation. The clinical outcome measured with Harris hip score and Barthel Index at the time of final follow-up was significantly different between the groups. CONCLUSION: Hip hemiarthroplasty for elderly patients with unstable intertrochanteric fracture can meet the load bearing requirement at early stage and reduce postoperative complications prominently. Moreover, GTR devices can effectively solve the instability problem of posterior-lateral side of hip caused by displacement of greater trochanter in unstable intertrochanteric fracture. PMID- 26351082 TI - Determination of Voriconazole Concentrations in Serum by GC-MS. AB - BACKGROUND: Voriconazole is a broad spectrum triazole antifungal drug used to treat systemic fungal infections. Therapeutic drug monitoring of voriconazole is necessary for achieving maximal efficiency without inducing toxic side effects. Other publications have reported methods for measuring voriconazole in serum using high-performance liquid chromatography (HPLC) and liquid chromatography tandem mass spectrometry (LC-MS/MS). Here, we report for the first time a method for the measurement of voriconazole in serum samples using gas chromatography mass spectrometry (GC-MS). METHODS: Protein precipitation with methanol was used to extract the antifungal that was derivatized with BSTFA (Sigma-Aldrich, St. Louis, MO) and analyzed by GC-MS. Linearity, sensitivity, precision, accuracy, and drug interferences were evaluated for this assay. RESULTS: Our method was linear up to 10 MUg/ml of voriconazole. The LOQ was determined to be 0.4 MUg/ml. CV for between-day precision was <12%. Correlation with an established LC-MS/MS yielded a R2 of 0.96. Tested drugs did not result in >10% error in measurement. CONCLUSION: To our knowledge, we report here the first GC-MS method for voriconazole measurement with acceptable performance. We hope that this method allows clinical laboratories without HPLC or LC-MS/MS instrumentation to measure voriconazole. PMID- 26351083 TI - Building links between town and gown: an innovative organisation in south-eastern Melbourne. AB - Primary care is the foundation of a nation's health care system. Real world research is a requirement of a health system built to deliver the benefits of a strong primary care community. In the last decade, new approaches to optimising the impact of research on practice and policy have been formulated across disciplines. However, in Australia, the primary care research community remains small and primary care researchers are not well represented in either receiving support for or governing research. While practice-based research networks (PBRNs) have brought GPs and, sometimes, other clinicians together with academics, few have managed to bring local decision makers and other primary health care stakeholders into partnerships where they can work together on common problems. This paper outlines a novel three-way partnership between a health authority, a primary care organisation and a university in the south-eastern suburbs of Melbourne. A case study was undertaken based on author experience of the Southern Academic Primary Care Research Unit (SAPCRU) and semi-structured interviews with representatives from partner organisations. Interviews elicited perceived barriers and facilitators, including complex financial, human resources and governance challenges, associated with bridging the gap between research and practice. It was found that SAPCRU has been successful in engaging with research partners and has begun to develop links with policy makers and orient research themes to the needs of its varied communities. Especially with the introduction of Primary Health Networks (PHNs), the model has the potential to translate to different settings but barriers should be noted. PMID- 26351085 TI - Relationship between velvet antler ossification and PTH and androgen serum levels in Tarim Red deer (Cervus elaphus). AB - Ossification degree is one of the primary variables affecting the medicinal value of velvet antler. Multiple factors regulate the calcification of velvet antler. We studied the relationship between the ossification of velvet antlers and the serum levels of parathyroid hormone (PTH) and androgen (ADG) in Tarim red deer. Enzyme-linked immunosorbent assays (ELISA) and atomic absorption spectrometry demonstrated that the changes in serum PTH and ADG levels nearly paralleled antler ossification during Tarim red deer antler mineralization. These results suggest that regulating the levels of serum PTH and ADG could decrease the calcification rate of velvet antlers in Tarim red deer. We conclude that PTH might increase antler ossification via the cAMP signaling pathway, and ADG possesses the dual roles of promoting both antler ossification and growth in Tarim red deer. This study suggests that we might be able to artificially control antler ossification to improve its medical value via the PTH or/and ADG pathway. J. Exp. Zool. 323A: 696-703, 2015. (c) 2015 Wiley Periodicals, Inc. PMID- 26351084 TI - beta-Amyrin Biosynthesis: The Methyl-30 Group of (3S)-2,3-Oxidosqualene Is More Critical to Its Correct Folding To Generate the Pentacyclic Scaffold than the Methyl-24 Group. AB - Oxidosqualene cyclases catalyze the transformation of oxidosqualene (1) into numerous cyclic triterpenes. Enzymatic reactions of 24-noroxidosqualene (8) and 30-noroxidosqualene (9) with Euphorbia tirucalli beta-amyrin synthase were conducted to examine the role of the branched methyl groups of compound 1 in the beta-amyrin biosynthesis. Substrate 8 almost exclusively afforded 30-nor-beta amyrin (>95.5 %), which was produced through a normal cyclization pathway, along with minor products (<4.5 %). However, a lack of the Me-30 group (analogue 9) resulted in significantly high production of premature cyclization products, including 6/6/6/5-fused tetracyclic and 6/6/6/6/5-fused pentacyclic skeletons (64.6 %). In addition, the fully cyclized product (35.4 %) having the 6/6/6/6/6 fused pentacycle was produced; however, the normally cyclized product, 29-nor beta-amyrin was present in only 18.6 % of these products. The conversion yield of substrate 8 possessing a Z-Me group at the terminus was approximately twofold greater than that of compound 9 with an E-Me group. Thus, the Me-30 group is essential for the correct folding of a chair-chair-chair-boat-boat conformation of compound 1 for the production of the beta-amyrin scaffold, whereas the Me-24 group exerts little influence on the normal polycyclization cascade. Here, we show that the Me-30 group plays critical roles in constructing the ordered architecture of a chair-chair-chair-boat-boat structure, in facilitating the ring expansion reactions, and in performing the final deprotonation reaction at the correct position. PMID- 26351086 TI - Nocturia: risk factors and associated comorbidities; findings from the EpiLUTS study. AB - OBJECTIVE: To evaluate the risk factors and comorbidities associated with nocturia in men and women aged >= 40 years. MATERIAL AND METHODS: The EpiLUTS study was an Internet-based cross-sectional, population-representative survey involving 30,000 men and women from the USA, UK and Sweden evaluating lower urinary tract symptoms (LUTS) using the LUTS Tool. A secondary analysis of the EpiLUTS data using participants with nocturia was performed. Descriptive statistics were used to examine the data. Logistic regressions were used to analyse associations of comorbid conditions and risk factors in men and women with nocturia >= 2. RESULTS: With a 59% response rate, nocturia >= 1 was quite common at 69% in men and 76% in women; 28% men and 34% women had nocturia >= 2. Age, body mass index (in women), Hispanic and Black responders, diabetes, high blood pressure, anxiety and depression and a history of bed-wetting were significantly associated with nocturia >= 2. Arthritis, asthma, diabetes, heart disease, inflammatory bowel disease, bladder infection, uterine prolapse, hysterectomy and menopausal status were all significantly associated with nocturia >= 2 in women. Prostatitis and prostate cancer were significant in men with nocturia >= 2. British and Swedish participants had a lesser risk of nocturia >= 2. CONCLUSION: Nocturia is a highly prevalent condition associated with various risk factors and comorbidities. Treatment of nocturia should be aimed at these causes in a multidisciplinary fashion. Further studies are needed to look specifically at these conditions in the pathophysiology of nocturia. PMID- 26351077 TI - Dissecting Complex and Multifactorial Nature of Alzheimer's Disease Pathogenesis: a Clinical, Genomic, and Systems Biology Perspective. AB - Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by loss of memory and other cognitive functions. AD can be classified into familial AD (FAD) and sporadic AD (SAD) based on heritability and into early onset AD (EOAD) and late onset AD (LOAD) based on age of onset. LOAD cases are more prevalent with genetically complex architecture. In spite of significant research focused on understanding the etiological mechanisms, search for diagnostic biomarker(s) and disease-modifying therapy is still on. In this article, we aim to comprehensively review AD literature on established etiological mechanisms including role of beta-amyloid and apolipoprotein E (APOE) along with promising newer etiological factors such as epigenetic modifications that have been associated with AD suggesting its multifactorial nature. As genomic studies have recently played a significant role in elucidating AD pathophysiology, a systematic review of findings from genome-wide linkage (GWL), genome-wide association (GWA), genome-wide expression (GWE), and epigenome-wide association studies (EWAS) was conducted. The availability of multi-dimensional genomic data has further coincided with the advent of computational and network biology approaches in recent years. Our review highlights the importance of integrative approaches involving genomics and systems biology perspective in elucidating AD pathophysiology. The promising newer approaches may provide reliable means of early and more specific diagnosis and help identify therapeutic interventions for LOAD. PMID- 26351087 TI - Rationale and design of the Helping Ease Renal failure with Bupi Yishen compared with the Angiotensin II Antagonist Losartan (HERBAAL) trial: a randomized controlled trial in non-diabetes stage 4 chronic kidney disease. AB - BACKGROUND: Chronic kidney disease (CKD) is a global public health problem. Currently, as for advanced CKD populations, medication options limited in angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB), which were partially effective. A Chinese herbal compound, Bupi Yishen formula, has showed renal protective potential in experiments and retrospective studies. This study will evaluate the efficacy and safety of Bupi Yishen formula (BYF) in patients with CKD stage 4. DESIGN: In this double blind, double dummy, randomized controlled trial (RCT), there will be 554 non-diabetes stage 4 CKD patients from 16 hospitals included and randomized into two groups: Chinese medicine (CM) group or losartan group. All patients will receive basic conventional therapy. Patients in CM group will be treated with BYF daily while patients in control group will receive losartan 100 mg daily for one year. The primary outcome is the change in estimated glomerular filtration rate (eGFR) over 12 months. Secondary outcomes include the incidence of endpoint events, liver and kidney function, urinary protein creatinine ratio, cardiovascular function and quality of life. DISCUSSION: This study will be the first multi-center, double blind RCT to assess whether BYF, compared with losartan, will have beneficial effects on eGFR for non-diabetes stage 4 CKD patients. The results will help to provide evidence-based recommendations for clinicians. TRIAL REGISTRATION: Chinese Clinical Trial Registry Number: ChiCTR-TRC-10001518 . PMID- 26351088 TI - Magnesium Status in Alzheimer's Disease: A Systematic Review. AB - The interest in poor magnesium (Mg) status as risk factor for Alzheimer's disease (AD) is increasing due to its antioxidant and neuroprotective properties. A systematic PubMed literature search of studies investigating Mg status was undertaken comparing AD to healthy controls (HCs) or patients with medical illness (medical controls [MCs]). Standardized mean differences (SMDs) +/- 95% confidence intervals (CIs) were calculated for all outcomes. Of 192 potentially eligible studies, 13 were included (559 patients with AD, 381 HCs, and 126 MCs). Compared to HCs, patients with AD had significantly lower Mg in cerebrospinal fluid (2 studies; SMD = -0.35;P= .02) and in hair (2 studies; SMD = -0.75;P= .0001). No differences between AD and controls were evident for serum Mg. In conclusion, AD seems to be associated with a lower Mg status when compared to HCs, while the scarcity of studies limited the findings about MCs. PMID- 26351089 TI - Diamond synthesis from carbon nanofibers at low temperature and low pressure. AB - In this article, we report a new route to synthesize diamond by converting "solid" carbon nanofibers with a Spark Plasma Sintering system under low temperature and pressure (even at atmospheric pressure). Well-crystallized diamond crystals are obtained at the tips of the carbon nanofibers after sintering at 1500 degrees C and atmospheric pressure. Combining with scanning electron microscopy, transmission electron microscopy, electron-energy loss spectroscopy and Raman spectroscopy observations, we propose the conversion mechanism as follows: the disorder "solid" carbon nanofibers->well crystallined carbon nanofibers->bent graphitic sheets->onion-liked rings->diamond single crystal->the bigger congregated diamond crystal. It is believed that the plasma generated by low-voltage, vacuum spark, via a pulsed DC in Spark Plasma Sintering process, plays a critical role in the low temperature and low pressure diamond formation. This Spark Plasma Sintering process may provide a new route for diamond synthesis in an economical way to a large scale. PMID- 26351090 TI - Radiofrequency Catheter Ablation for Atrial Fibrillation Elicited "Jackhammer Esophagus": A New Complication Due to Vagal Nerve Stimulation? AB - Radiofrequency catheter ablation (RFCA) is a potentially curative method for treatment of highly symptomatic and drug-refractory atrial fibrillation (AF). However, this technique can provoke esophageal and nerve lesion, due to thermal injury. To our knowledge, there have been no reported cases of a newly described motor disorder, the Jackhammer esophagus (JE) after RFCA, independently of GERD. We report a case of JE diagnosed by high-resolution manometry (HRM), in whom esophageal symptoms developed 2 weeks after RFCA, in absence of objective evidence of GERD. A 65-year-old male with highly symptomatic, drug-refractory paroxysmal AF was candidate to complete electrical pulmonary vein isolation with RFCA. Prior the procedure, the patient underwent HRM and impedance-pH to rule out GERD or hiatal hernia presence. All HRM parameters, according to Chicago classification, were within normal limits. No significant gastroesophageal reflux was documented at impedance pH monitoring. Patient underwent RFCA with electrical disconnection of pulmonary vein. After two weeks, patient started to complain of dysphagia for solids, with acute chest-pain. The patient repeated HRM and impedance-pH monitoring 8 weeks after RFCA. HRM showed in all liquid swallows the typical spastic hypercontractile contractions consistent with the diagnosis of JE, whereas impedance-pH monitoring resulted again negative for GERD. Esophageal dysmotility can represent a possible complication of RFCA for AF, probably due to a vagal nerve injury, and dysphagia appearance after this procedure must be timely investigated by HRM. PMID- 26351091 TI - Comparing the Areas of Interest in the Field of Functional Gastrointestinal Disorder and Neurogastroenterology and Motility Between the East and the West. AB - There is a paucity of studies that compare the differences in published articles submitted from the East and the West in the area of neurogastroenterology and motility (NM). To compare the article topics from the East and the West which have been published, 5 Western (Gastroenterology, Gut, American Journal of Gastroenterology, American Journal of Physiology-Gastrointestinal and Liver Physiology, and Neurogastroenterology and Motility) and 3 Eastern gastrointestinal journals (Journal of Gastroenterology, Journal of Gastroenterology and Hepatology, and Journal of Neurogastroenterology and Motility) were selected based on the impact factor. Published papers were classified into 12 categories and 60 subcategories. The titles and abstracts of review articles, original articles, and meta-analyses from these journals were reviewed for the last 2 years (2013-2014). In case of Journal of Neurogastroenterology and Motility which is published quarterly, this search was performed for 5 years (2010-2014). Of the total 2656 reviewed articles, 842 (260 from the East and 582 from the West) were classified into the category of NM. The most frequently published papers from the Western researchers were categorized as brain-gut interaction, visceral hypersensitivity, and irritable bowel syndrome, whereas those from the Eastern researchers were categorized as gastroesophageal reflux disease, functional dyspepsia, and irritable bowel syndrome. This difference between the East and the West is not just due to the journal itself, but it also depends on the author's affiliation and their ability to perform high quality research in the area of the NM. These data provide evidence for the research trend and give valuable information to the researchers for determining subjects for the study and for selecting proper journals for publishing their studies. PMID- 26351092 TI - Retraction: Herndon J.M. Evidence of Coal-Fly-Ash Toxic Chemical Geoengineering in the Troposphere: Consequences for Public Health. Int. J. Environ. Res. Public Health 2015, 12, 9375-9390. PMID- 26351093 TI - Refugees pose little health risk, says WHO. PMID- 26351094 TI - Direct evidence from intraoperative electrocortical stimulation indicates shared and distinct speech production center between Chinese and English languages. AB - Chinese processing has been suggested involving distinct brain areas from English. However, current functional localization studies on Chinese speech processing use mostly "indirect" techniques such as functional magnetic resonance imaging and electroencephalography, lacking direct evidence by means of electrocortical recording. In this study, awake craniotomies in 66 Chinese speaking glioma patients provide a unique opportunity to directly map eloquent language areas. Intraoperative electrocortical stimulation was conducted and the positive sites for speech arrest, anomia, and alexia were identified separately. With help of stereotaxic neuronavigation system and computational modeling, all positive sites elicited by stimulation were integrated and a series of two- and three-dimension Chinese language probability maps were built. We performed statistical comparisons between the Chinese maps and previously derived English maps. While most Chinese speech arrest areas located at typical language production sites (i.e., 50% positive sites in ventral precentral gyrus, 28% in pars opercularis and pars triangularis), which also serve English production, an additional brain area, the left middle frontal gyrus (Brodmann's areas 6/9), was found to be unique in Chinese production (P < 0.05). Moreover, Chinese speakers' inferior ventral precentral gyrus (Brodmann's area 6) was used more than that in English speakers. Our finding suggests that Chinese involves more perisylvian region (extending to left middle frontal gyrus) than English. This is the first time that direct evidence supports cross-cultural neurolinguistics differences in human beings. The Chinese language atlas will also helpful in brain surgery planning for Chinese-speakers. PMID- 26351095 TI - Do all men with pathological Gleason score 8-10 prostate cancer have poor outcomes? Results from the SEARCH database. AB - OBJECTIVE: To determine whether there are subsets of men with pathological high grade prostate cancer (Gleason score 8-10) with particularly high or low 2-year biochemical recurrence (BCR) risk after radical prostatectomy (RP) when stratified into groups based on combinations of pathological features, such as surgical margin status, extracapsular extension (ECE) and seminal vesicle invasion (SVI). MATERIALS AND METHODS: We identified 459 men treated with RP with pathological Gleason score 8-10 prostate cancer in the SEARCH database. The men were stratified into five groups based on pathological characteristics: group 1, men with negative surgical margins (NSMs) and no ECE; group 2, men with positive surgical margin (PSMs) and no ECE; group 3, men with NSMs and ECE; group 4, men with PSMs and ECE; and group 5, men with SVI. Cox proportional hazards models and the log-rank test were used to compare BCR among the groups. RESULTS: At 2 years after RP, pathological group was significantly correlated with BCR (log-rank, P < 0.001) with patients in group 5 (+SVI) having the highest BCR risk (66%) and those in group 1 (NSMs and no ECE) having the lowest risk (14%). When we compared groups 2, 3, and 4, with each other, there was no significant difference in BCR among the groups (~50% 2-year BCR risk; log-rank P = 0.28). Results were similar when adjusting for prostate-specific antigen, age, pathological Gleason sum and clinical stage, or after excluding men who received adjuvant therapy. CONCLUSIONS: In patients with high grade (Gleason score 8-10) prostate cancer after RP, the presence of either PSMs, ECE or SVI was associated with an increased risk of early BCR, with a 2-year BCR risk of >=50%. Conversely, men with organ-confined margin-negative disease had a very low risk of early BCR despite Gleason score 8-10 disease. PMID- 26351096 TI - Aerobic Asymmetric Dehydrogenative Cross-Coupling between Two C(sp3)-H Groups Catalyzed by a Chiral-at-Metal Rhodium Complex. AB - A sustainable C-C bond formation is merged with the catalytic asymmetric generation of one or two stereocenters. The introduced catalytic asymmetric cross coupling of two C(sp3)-H groups with molecular oxygen as the oxidant profits from the oxidative robustness of a chiral-at-metal rhodium(III) catalyst and exploits an autoxidation mechanism or visible-light photosensitized oxidation. In the latter case, the catalyst serves a dual function, namely as a chiral Lewis acid for catalyzing enantioselective enolate chemistry and at the same time as a visible-light-driven photoredox catalyst. PMID- 26351097 TI - Risk Stratification for Ventricular Tachyarrhythmias by Ambulatory Electrocardiogram-Based Frequency Domain T-Wave Alternans. AB - BACKGROUND: Ambulatory electrocardiogram (ECG)-based T-wave alternans (TWA) quantified by the modified moving average method (MMA) can be used to identify patients at risk for sudden cardiac death. However, there is no information available on ambulatory ECG-based TWA as quantified by the frequency domain (FD) method to identify patients with an implantable cardioverter defibrillator (ICD) who are at high risk for ventricular tachyarrhythmias. Further, there are few data regarding the comparison of clinical utility of FD-TWA with MMA-TWA, heart rate variability (HRV), and heart rate turbulence (HRT). METHODS AND RESULTS: In 41 patients with ICD, of whom 14 patients had a past history of at least one appropriate ICD discharge, FD-TWA, MMA-TWA, HRV, and HRT were analyzed from 24 hour Holter ECG monitoring recordings. Only positive results of FD-TWA and abnormal HRV (standard deviation of all normal-to-normal intervals <=111 ms) were significantly more frequently observed in patients with than without appropriate ICD discharge. Patients with FD-TWA positive had a significantly higher risk of appropriate ICD discharge than those with FD-TWA negative (50% vs 16%; odds ratio, 5.3 [95% confidence interval, 1.2-23.7], P = 0.02). When FD-TWA and HRV were combined, the specificity (93% vs 59%, P = 0.003) and predictive accuracy (83% vs 66%, P = 0.07) for the identification of patients with appropriate ICD discharge were greater than those for FD-TWA only. CONCLUSION: The ambulatory ECG based FD-TWA might be useful to detect patients with ICD who are at high risk for ventricular tachyarrhythmias, and the combination of FD-TWA and HRV might improve the ability to detect such high-risk patients. PMID- 26351098 TI - The role of interpersonal movement synchronisation in empathic functions: Insights from Tango Argentino and Capoeira. AB - Although evidence points to a role for kinesthetic empathy (i.e. spontaneous interpersonal movement imitation and synchronisation) in social interaction, its relationship with emotional and cognitive aspects of empathy is unknown. We compared empathy in Tango and Capoeira experts, which crucially depend on ongoing, mutual interpersonal synchronisation, with empathy in practitioners of Salsa and Breakdance, respectively, which demand less interpersonal synchronisation but are comparable concerning movements and setting. Kinesthetic empathy was increased in the Tango and Capoeira groups. Although no group differences in other aspects of empathy were detected, kinesthetic empathy correlated with emotional and cognitive empathy. Taken together, trait kinesthetic empathy varies in the general population, and appears increased in synchronisation experts. PMID- 26351099 TI - Self-Heating Effects In Polysilicon Source Gated Transistors. AB - Source-gated transistors (SGTs) are thin-film devices which rely on a potential barrier at the source to achieve high gain, tolerance to fabrication variability, and low series voltage drop, relevant to a multitude of energy-efficient, large area, cost effective applications. The current through the reverse-biased source barrier has a potentially high positive temperature coefficient, which may lead to undesirable thermal runaway effects and even device failure through self heating. Using numerical simulations we show that, even in highly thermally confined scenarios and at high current levels, self-heating is insufficient to compromise device integrity. Performance is minimally affected through a modest increase in output conductance, which may limit the maximum attainable gain. Measurements on polysilicon devices confirm the simulated results, with even smaller penalties in performance, largely due to improved heat dissipation through metal contacts. We conclude that SGTs can be reliably used for high gain, power efficient analog and digital circuits without significant performance impact due to self-heating. This further demonstrates the robustness of SGTs. PMID- 26351100 TI - The impact of preventive screening resource distribution on geographic and population-based disparities in colorectal cancer in Mississippi. AB - BACKGROUND: The state of Mississippi has the highest colorectal cancer (CRC) mortality rate in the USA. The geographic distribution of CRC screening resources and geographic- and population-based CRC characteristics in Mississippi are investigated to reveal the geographic disparity in CRC screening. METHODS: The primary practice sites of licensed gastroenterologists and the addresses of licensed medical facilities offering on-site colonoscopies were verified via telephone surveys, then these CRC screening resource data were geocoded and analyzed using Geographic Information Systems. Correlation analyses were performed to detect the strength of associations between CRC screening resources, CRC screening behavior and CRC outcome data. RESULTS: Age-adjusted colorectal cancer incidence rates, mortality rates, mortality-to-incidence ratios, and self reported endoscopic screening rates from the years 2006 through 2010 were significantly different for Black and White Mississippians; Blacks fared worse than Whites in all categories throughout all nine Public Health Districts. CRC screening rates were negatively correlated with CRC incidence rates and CRC mortality rates. The availability of gastroenterologists varied tremendously throughout the state; regions with the poorest CRC outcomes tended to be underserved by gastroenterologists. CONCLUSIONS: Significant population-based and geographic disparities in CRC screening behaviors and CRC outcomes exist in Mississippi. The effects of CRC screening resources are related to CRC screening behaviors and outcomes at a regional level, whereas at the county level, socioeconomic factors are more strongly associated with CRC outcomes. Thus, effective control of CRC in rural states with high poverty levels requires both adequate preventive CRC screening capacity and a strategy to address fundamental causes of health care disparities. PMID- 26351101 TI - Anti-sickling Activity of Ursolic Acid Isolated from the Leaves of Ocimum gratissimum L. (Lamiaceae). AB - The present study reports in vitro anti-sickling activity and phytochemical analyses of the leaves of Ocimum gratissimum. Biological testing revealed that the plant extracts possess antisickling effects. The combination of spectroscopic techniques: 1D-NMR, 2D-NMR and MS revealed that ursolic acid is the major biologically active compound of O. gratissimum (Silva et al. in Molecules 13:2482 2487, 2008; Kedar et al. J Food Drug Anal 20:865-871, 2012). This study is the first report of the antisickling activity of ursolic acid isolated from O. gratissimum. The pharmaceutical relevance of findings from this study derives from the possibility of integrating O. gratissimum as an antisickling plant in the pharmacopoeia of Democratic Republic of the Congo. The identification of the active principle could enhance the standardization of antisickling recipe. PMID- 26351102 TI - Three New Triterpenoids from European Mushroom Tricholoma terreum. AB - Three rare triterpenoids, saponaceolides Q-S (1-3), have been isolated from fruiting bodies of the mushroom Tricholoma terreum. Their structures were characterized based on extensive spectroscopic data. Compound 1 showed certain cytotoxicities against four human tumor cell lines. PMID- 26351103 TI - Burning Bridges: Mechanisms and Implications of Endovascular Failure in the Treatment of Peripheral Artery Disease. PMID- 26351104 TI - Dynamically stabilized magnetic skyrmions. AB - Magnetic skyrmions are topologically non-trivial spin textures that manifest themselves as quasiparticles in ferromagnetic thin films or noncentrosymmetric bulk materials. So far attention has focused on skyrmions stabilized either by the Dzyaloshinskii-Moriya interaction (DMI) or by dipolar interaction, where in the latter case the excitations are known as bubble skyrmions. Here we demonstrate the existence of a dynamically stabilized skyrmion, which exists even when dipolar interactions and DMI are absent. We establish how such dynamic skyrmions can be nucleated, sustained and manipulated in an effectively lossless medium under a nanocontact. As quasiparticles, they can be transported between two nanocontacts in a nanowire, even in complete absence of DMI. Conversely, in the presence of DMI, we observe that the dynamical skyrmion experiences strong breathing. All of this points towards a wide range of skyrmion manipulation, which can be studied in a much wider class of materials than considered so far. PMID- 26351105 TI - EURO-MUSCULUS/USPRM. Basic scanning protocols for knee. AB - In this protocol, the patient/probe positionings, anatomical drawings and ultrasound images of commonly scanned knee structures are described. This practical guide is prepared (with an international consensus of several expert physiatrists) to serve as a uniform/standard approach especially for beginner sonographers. PMID- 26351106 TI - EURO-MUSCULUS/USPRM. Basic Scanning Protocols for Ankle and foot. AB - In this protocol, the patient/probe positionings, anatomical drawings and ultrasound images of commonly scanned ankle/foot structures are described. This practical guide is prepared (with an international consensus of several expert physiatrists) to serve as a uniform/standard approach especially for beginner sonographers. PMID- 26351107 TI - EURO-MUSCULUS/USPRM. Basic scanning protocols for hip. AB - In this protocol, the patient/probe positionings, anatomical drawings and ultrasound images of commonly scanned hip structures are described. This practical guide is prepared (with an international consensus of several expert physiatrists) to serve as a uniform/standard approach especially for beginner sonographers. PMID- 26351108 TI - Serum amyloid-beta levels are increased in patients with obstructive sleep apnea syndrome. AB - A critical link between amyloid-beta (Abeta) and hypoxia has been demonstrated in in vitro and animal studies but has not yet been proven in humans. Obstructive sleep apnea syndrome (OSAS) is a common disorder that is characterized by nocturnal intermittent hypoxaemia. This study sought to examine the association between the chronic intermittent hypoxia and Abeta in OSAS patients. Forty-five cognitively normal OSAS patients and forty-nine age- and gender-matched subjects diagnosed with simple snoring and not OSAS were included in the present study. Serum Abeta40, Abeta42, total tau and phosphorylated tau 181 (P-tau 181) levels were measured using ELISA kits. All subjects were evaluated with nighttime polysomnography and cognitive tests. Compared with the controls, the OSAS patients exhibited significantly higher serum Abeta40, Abeta42 and total Abeta levels, and each of these levels was positively correlated with the apnea hypopnea index, the oxygen desaturation index, and the mean and lowest oxyhaemoglobin saturations in the OSAS patients. Moreover, the OSAS patients exhibited strikingly higher serum P-tau 181 levels, and these levels were positively correlated with serum Abeta levels. This study suggests that there is an association between chronic intermittent hypoxia and increased Abeta levels, implying that hypoxia may contribute to the pathogenesis of Alzheimer's disease. PMID- 26351109 TI - Ice Regelation: Hydrogen-bond extraordinary recoverability and water quasisolid phase-boundary dispersivity. AB - Regelation, i.e., ice melts under compression and freezes again when the pressure is relieved, remains puzzling since its discovery in 1850's by Faraday. Here we show that hydrogen bond (O:H-O) cooperativity and its extraordinary recoverability resolve this anomaly. The H-O bond and the O:H nonbond possesses each a specific heat etax(T/ThetaDx) whose Debye temperature ThetaDx is proportional to its characteristic phonon frequency omegax according to Einstein's relationship. A superposition of the etax(T/ThetaDx) curves for the H O bond (x=H, omegaH~3200 cm(-1)) and the O:H nonbond (x=L, omegaL~200 cm(-1), ThetaDL=198 K) yields two intersecting temperatures that define the liquid/quasisolid/solid phase boundaries. Compression shortens the O:H nonbond and stiffens its phonon but does the opposite to the H-O bond through O-O Coulomb repulsion, which closes up the intersection temperatures and hence depress the melting temperature of quasisolid ice. Reproduction of the Tm(P) profile clarifies that the H-O bond energy EH determines the Tm with derivative of EH=3.97 eV for bulk water and ice. Oxygen atom always finds bonding partners to retain its sp3-orbital hybridization once the O:H breaks, which ensures O:H-O bond recoverability to its original state once the pressure is relieved. PMID- 26351111 TI - Engineering overexpression of ORCA3 and strictosidine glucosidase in Catharanthus roseus hairy roots increases alkaloid production. AB - Catharanthus roseus produces many pharmaceutically important terpenoid indole alkaloids (TIAs) such as vinblastine, vincristine, ajmalicine, and serpentine. Past metabolic engineering efforts have pointed to the tight regulation of the TIA pathway and to multiple rate-limiting reactions. Transcriptional regulator ORCA3 (octadecanoid responsive Catharanthus AP2-domain protein), activated by jasmonic acid, plays a central role in regulating the TIA pathway. In this study, overexpressing ORCA3 under the control of a glucocorticoid-inducible promoter in C. roseus hairy roots resulted in no change in the total amount of TIAs measured. RT-qPCR results showed that ORCA3 overexpression triggered the upregulation of transcripts of most of the known TIA pathway genes. One notable exception was the decrease in strictosidine glucosidase (SGD) transcripts. These results corresponded to previously published results. In this study, ORCA3 and SGD were both engineered in hairy roots under the control of a glucocorticoid-inducible promoter. Co-overexpression of ORCA3 and SGD resulted in a significant (p < 0.05) increase in serpentine by 44 %, ajmalicine by 32 %, catharanthine by 38 %, tabersonine by 40 %, lochnericine by 60 % and horhammericine by 56 % . The total alkaloid pool was increased significantly by 47 %. Thus, combining overexpression of a positive regulator and a pathway gene which is not controlled by this regulator provided a way to enhance alkaloid production. PMID- 26351112 TI - Custom 3D-printed acetabular implants in hip surgery--innovative breakthrough or expensive bespoke upgrade? AB - Custom 3D-printed triflange acetabular cages are a new option in the armamentarium of the revision hip surgeon. This review article defines this technology, its indications, surgical method, advantages, disadvantages, use, current published literature and future applications. PMID- 26351113 TI - Plasma ghrelin and von Willebrand Factor levels in non-traumatic osteonecrosis of femoral head. PMID- 26351114 TI - Late complications and long-term outcomes following aseptic revision of a hip arthroplasty performed for oncological resection. AB - PURPOSE: In order to achieve an oncological margin during limb salvage surgery for tumours around the hip, part or the entire hip joint is frequently sacrificed. Hip arthroplasty restores a functional extremity and achieves limb salvage. Currently there is a paucity of data concerning the late complications, long-term survival, and the risks of re-revision following aseptic revision of a total hip arthroplasty (THA) performed following an oncological resection. METHODS: We identified 78 patients who underwent aseptic revision of a THA which was performed for an oncological process involving the hip from 1972 to 2006. All patients had a minimum 5 years of follow-up with a mean of 13 years. Outcomes were compared to 1,378 patients undergoing aseptic revision of a THA that was performed for a diagnosis of osteoarthritis. RESULTS: The mean 5-, 10-, 15-, and 20-year re-revision-free survival for an oncologic process of the hip was 100%, 85%, 69%, and 57%. Within this cohort, younger patients were at an increased risk of revision surgery. There was no difference in survivorship of the revision implant at any of the aforementioned time points between the oncologic and osteoarthritis cohorts. Patients with an oncologic diagnosis had a higher rate of dislocations, component wear, and loosening compared to the osteoarthritis group. CONCLUSION: Late complications following revision surgery of THA performed for an oncologic resection are common. The results of this study provide information for counselling patients on implant survivorship and complications following aseptic revision THA after index surgery for an oncologic indication. PMID- 26351115 TI - Alendronate stimulates osteoprotegerin expression in fibroblasts from periprosthetic membrane. AB - PURPOSE: Aseptic loosening of an implant after total joint arthroplasty is still a major complication that results from periprosthetic osteolysis. Fibroblasts in the interface membrane express receptor activator of nuclear factor kappa B ligand (RANKL) and stimulate osteoclast formation. Studies demonstrate that through the control of osteoclastic bone loss bisphosphonates inhibit wear particle-induced bone resorption around total hip arthroplasty. The majority of bisphosphonates studies have focused on their effects on osteoblasts and osteoclasts. Little attention has been paid to their action on fibroblasts. METHODS: We isolated fibroblasts from the interface membrane that was obtained when revision hip arthroplasty was performed because of aseptic loosening. Fibroblasts were stimulated with alendronate. RANKL and osteoprotegerin (OPG) assays were performed using enzyme-linked immunosorbent assay kit and real time Reverse Transcription- Polymerase Chain Reaction (RT-PCR). RESULTS: We found that alendronate stimulated OPG mRNA and protein expression in a time and dose dependent manner. By contrast, alendronate did not affect RANKL expression. CONCLUSIONS: The results indicate that alendronate modulated OPG production by fibroblasts from periprosthetic membrane, which may prove helpful for the inhibition of bone loss during aseptic loosening following total joint arthroplasty. PMID- 26351116 TI - Conversion arthroplasty of the hip: mid-term results are good. AB - The historical mid-term results of conversion total hip arthroplasty (THA) are acceptable; however, the complication rates are high. In total, 39 patients (45 hips) from 2 institutions underwent conversion THA from 1993-2006 and were retrospectively evaluated. The mean age was 48.3 years, the mean follow-up time was 8.7 years, and the mean duration arthrodesis prior to conversion THA was 18.2 years. The outcomes included operative time, blood loss, leg-length discrepancy (LLD), thigh circumference, Harris Hip Score (HHS), complications, and radiographic evaluation. A total of 34 THAs were cemented, and 11 were uncemented. The mean operative time was 102 minutes, and the mean blood loss was 1019 ml. The mean HHS improved from 32.4 to 82.5 (p<0.01). The mean LLD decreased from 4.2 to 1.1 cm, while the thigh circumference increased by a mean of 1.6 cm. Complications included: a positive Trendelenburg gait (6), early haematoma that required surgical evacuation (5), dislocation (2), deep infection (1), and early aseptic loosening of the components (2). In conclusion, the functional results of the conversion THA using predominantly cemented components are good at mid-term follow-up; although the complication rates remain higher than a standard primary THA, aseptic loosening rates of the cemented components is low at mid-term follow up. PMID- 26351117 TI - Vulvar necrosis after surgical treatment of femoral neck fracture: a case report and investigation of the mechanism of injury. AB - We report the case of a young patient, presenting with total bilateral vulvar necrosis after reduction of a femoral neck fracture. This report describes the management of this complication, its mechanism of injury and the associated means of prevention. We present an investigation of the vulvar vasculature in order to understand the mechanism of injury.The study of the vulvar vasculature rejects the anatomical hypothesis of selective damage to the internal and external arteries. Instead, it suggests intraoperative impingement of the terminal blood vessels caused by compression against the perineal post prompting discussion on the use of moulded countertraction posts during orthopaedic surgery. PMID- 26351118 TI - Factors associated with restricted hip extension during gait in women after total hip arthroplasty. AB - PURPOSE: A decreased peak hip extension angle in the late stance phase is a major gait abnormality in patients with THA. The purpose of this study was to determine the relationship between peak hip extension angle during gait and functional impairments such as muscle weakness and the limitation in joint range of motion and to identify the clinical factors influencing peak hip extension angle during gait. METHODS: 67 female volunteers with THA were examined. Biomechanical gait analysis was performed to measure peak hip extension angle during gait. Maximal isometric strength of the hip and knee, passive hip extension range of motion, leg length discrepancy, and hip pain were assessed. RESULTS: Peak hip extension angle during gait significantly correlated with passive hip extension range of motion (r = 0.259), hip pain (r = -0.264), isometric strengths of the hip musculature (r = 0.278-0.491), and knee extensor (r = 0.386). Stepwise multiple regression analysis revealed that hip abductor torque (beta = 0.355, P = 0.001), hip pain (beta = -0.353, P = 0.001), and passive hip extension range of motion (beta = 0.258, P = 0.011) were significant contributors to peak hip extension angle during gait (R2 = 0.408). CONCLUSIONS: Our findings suggest that THA rehabilitation aimed at improving gait ability should focus on strengthening the hip abductors, controlling hip pain and increasing range of motion of hip extension. PMID- 26351119 TI - The result of transmuscular versus transosseous repair of the posterior capsule on early dislocations in primary hip arthroplasty. AB - PURPOSE: Dislocation is a concerning complication of the posterolateral approach for total hip arthroplasty (THA). Use of a larger size femoral head and a correct repair of the posterior structures can reduce the risk on dislocation of the hip prosthesis. In this study we investigated if there was a difference in dislocation rate between transmuscular and transosseous repair of the posterior soft tissues with use of 36 mm heads. METHODS: A power analysis showed that with a standardised effect size of 0.3 and p-value of 0.05, each group should include at least 174 patients. A total of 465 consecutive primary THAs with a posterolateral approach were performed in patients with primary osteoarthritis by 3 orthopaedic surgeons. There were 246 patients operated using transmuscular repair, the other 219 by using transosseous repair. All patients were given the same prostheses. RESULTS: Dislocation rate was 1.7% in all patients with at least 1 year follow-up. No significant difference was found in dislocation between both reconstruction techniques. Clinical outcome scores were comparable between the groups. CONCLUSIONS: Transosseous and transmuscular repair were equally effective techniques in closing the posterior soft tissues after THA through the posterolateral approach, without difference in dislocation rate or complication rate. PMID- 26351120 TI - Frontal plane pelvic motion during gait captures hip osteoarthritis related disability. AB - Gait analysis has widely been accepted as an objective measure of function and clinical outcome. Ambulatory accelerometer-based gait analysis has emerged as a clinically more feasible alternative to optical motion capture systems but does not provide kinematic characterisation to identify disease dependent mechanisms causing walking disability. This study investigated the potential of a single inertial sensor to derive frontal plane motion of the pelvis (i.e. pelvic obliquity) and help identify hip osteoarthritis (OA) related gait alterations. Patients with advanced unilateral hip OA (n = 20) were compared to patients with advanced unilateral knee OA (n = 20) and to a healthy control group (n = 20). Kinematic characterisation of frontal plane pelvic motion during gait demonstrated decreased range of motion and increased asymmetry for hip OA patients specifically. PMID- 26351121 TI - Management of femoral bone loss in revision total hip arthroplasty. AB - Femoral bone loss is frequently encountered during revision total hip arthroplasty. The quality and quantity of remaining bone helps determine the best method for reconstruction. Extensively porous-coated cylindrical stems or titanium fluted tapered devices that achieve fixation in the diaphysis have both demonstrated excellent long-term survivorship. Titanium fluted tapered stems with a modular proximal body allow for more accurate leg length, offset, and version adjustments independent of the distal stem which may optimise hip biomechanics. Intraoperative fractures are more common with cylindrical stems and subsidence with tapered stems, particularly monoblock designs and in both dislocation continues to be one of the most common postoperative complications. In salvage situations in which an ectatic femoral canal is unable to support an uncemented device, impaction bone grafting, allograft-prosthetic composite, or a segmental proximal femoral replacement may be required. PMID- 26351122 TI - Making chromosome abnormalities treatable conditions. AB - Individuals affected by the classic chromosome deletion syndromes which were first identified at the beginning of the genetic age, are now positioned to benefit from genomic advances. This issue highlights five of these conditions (4p , 5p-, 11q-, 18p-, and 18q-). It focuses on the increased in understanding of the molecular underpinnings and envisions how these can be transformed into effective treatments. While it is scientifically exciting to see the phenotypic manifestations of hemizygosity being increasingly understood at the molecular and cellular level, it is even more amazing to consider that we are now on the road to making chromosome abnormalities treatable conditions. PMID- 26351123 TI - Efficient stress-relaxation in InGaN/GaN light-emitting diodes using carbon nanotubes. AB - A facile method to facilitate epitaxial lateral overgrowth (ELO) of gallium nitride (GaN) was developed by using single-walled carbon nanotubes (SWCNTs). High-quality GaN was achieved on sapphire by simply coating the SWCNTs as an intermediate layer for stress and defect mitigation. SWCNTs maintained their integrity at high reaction temperature and led to suppression of edge dislocations and biaxial stress relaxation by up to 0.32 GPa in a GaN template layer. InGaN/GaN multi-quantum-well light-emitting diodes (LEDs) on this high quality GaN template offered enhanced internal quantum efficiency and light output power with reduced efficiency droop. The method developed here has high potential to replace current ELO methods such as patterned sapphire substrates or buffer layers like SiO2 and SiNx. PMID- 26351124 TI - [Imaging techniques and pain]. AB - Over the last 15 years, functional brain imaging techniques have provided critical insights into cortical, subcortical and even spinal mechanisms involved in pain perception and pain modulation in humans. The pivotal contribution of brain imaging studies conducted in Germany have thereby been internationally acknowledged. One of the key challenges for the next decade is to shift the focus from studies in healthy volunteers to different clinical populations suffering from chronic pain to characterize CNS mechanisms, as well as neurobiological predictors and resilience factors of pain chronification. Ultimately, the knowledge gained by this work may help identify individual or syndrome-specific CNS changes as biomarkers to make therapeutic decisions. PMID- 26351126 TI - [Pain medicine yesterday, today, tomorrow: 40 years of the Deutsche Schmerzgesellschaft]. PMID- 26351125 TI - [Physiology of pain]. AB - Pain research is based broadly on physiological disciplines and its development follows the methodological progress of the era, from classical psychophysiology to electrophysiological investigations at peripheral and central nociceptive systems, single cells and ion channels to modern imaging of nociceptive processing. Physiological pain research in Germany has long been part of an interdisciplinary research network extending beyond all political boundaries, and this situation has continued since molecular techniques started to dominate all biomedical research. Current scientific questions, such as intracellular nociceptive signal mechanisms, interactions with other physiological systems including the immune system, or the genetic basis of epidemic and chronic pain diseases can only be solved interdisciplinary and with international collaboration. PMID- 26351127 TI - [Knowledge and attitude of medical students in Germany towards palliative care : Does the final year of medical school make a difference?]. AB - BACKGROUND: The practical year (PY) during the final year of medical education is intended to deepen and broaden knowledge, skills, and abilities that were acquired during previous years of their studies. Against this background, this study pursues the question of how the knowledge of future physicians and their confidence in terms of cancer pain therapy and other palliative care issues develops during the PY. MATERIALS AND METHODS: At the end of the PY, students from two university hospitals completed a 3-part online questionnaire (self assessment of the confidence, questions about palliative care knowledge, and assessment of palliative care training during the PY). These results are compared with previously published data from the same collective that had been collected at the beginning of the PY. RESULTS: Overall, 92 of 318 students participated (28.9 %). Less than 10 % of students said that they were more confident regarding palliative care topics at the end of their medical studies. Improvements in the self-assessment could only be observed in the recognition of and screening for cancer pain (increase from 36 % to 65%). With regard to the palliative care knowledge, only the knowledge of how to treat symptoms other than pain improved significantly; however, knowledge in this regard prior to the PY was particularly low (an increase from 25 % to 35 %, p < 0.05). In the only multiple-choice question about ethics, the correct answer rose slightly from 51 % (before) to 55 % (after the PY). Of participating students, 21% (prior to the PY 27 %) stated that not providing fluids to dying patients is a form of euthanasia. In terms of palliative care training, between 36 and 83 % of participants stated having insufficient opportunities to gain knowledge and experience on various topics in the treatment of patients with advanced and incurable diseases during their PY. CONCLUSION: In the present study, considerable deficits in confidence and knowledge regarding palliative care issues were also observed at the end of PY. Integration of palliative care into the medical school curriculums should be given special attention in terms of a longitudinal training of the PY. PMID- 26351128 TI - [Myofacial is not the same as myofascial]. PMID- 26351129 TI - [Generalist palliative care for non-cancer patients: A review article]. AB - BACKGROUND: Most patients in the last phase of life can be treated in the context of generalist palliative care, especially by general practitioners. In contrast to specialized palliative care, non-cancer patients predominate in this setting. OBJECTIVE: The aim of this article is to review the literature and elaborate current topics for non-cancer patients at the end of life in primary palliative care. MATERIAL AND METHODS: A literature search was carried out in the databases PubMed and Scopus from 2008 to 2013 followed by a qualitative content analysis according to the PRISMA statement. RESULTS: A total of 127 articles could be included in the qualitative content analysis and the final review whereby four core topics were identified: (1) specific target groups (e.g. elderly patients, patients with advanced heart failure and pain), (2) collaboration of general practitioners with other physicians and health professions, (3) qualifications in palliative care and (4) provision of primary palliative care. Most articles found were related to the fourth topic and the subtopic of barriers and facilitators of palliative care. Insufficient coordination of the persons involved was a barrier often discussed. Advanced care planning including concrete aspects of palliative care at an early stage can be beneficial for both patients and professionals. CONCLUSION: The current literature search elucidates the importance of optimizing the processes and structures in providing palliative care and the discussion of end of life issues at an early stage in general practice. Therefore, a structured identification of palliative care needs identified by appropriate assessment instruments is crucial. PMID- 26351130 TI - [Musculoskeletal pain]. AB - Among the clinically relevant pain conditions, pain in the musculoskeletal system is most frequent. This article reports extensive epidemiological data on musculoskeletal system pain in Germany and worldwide. Since back pain is most frequent, the diagnostics and therapeutic algorithms of acute, recurring, and chronic lower back pain in Germany will be particularly addressed. The importance of the physiologic-organic, the cognitive-emotional, the behavioral, and the social level to diagnostics and treatment will be discussed. We will also focus on osteoarthritic pain and address its epidemiology, clinical importance, and significance for the health care system. This article will list some reasons why the musculoskeletal system in particular is frequently the site of chronic pain. The authors believe that these reasons are to be sought in the complex structures of the musculoskeletal system; in the particular sensitivity of the deep somatic nociceptive system for long-term sensitization processes, as well as the ensuing nervous system reactions; and in the interactions between the nervous and immune systems. The article will give some insights into the research carried out on this topic in Germany. PMID- 26351131 TI - Impact of the ConRed program on different cyberbulling roles. AB - This article presents results from an evaluation of the ConRed cyberbullying intervention program. The program's impacts were separately determined for the different roles within cyberbullying that students can take, i.e., cyber-victims, cyber-bullies, cyber-bully/victims, and bystanders. The ConRed program is a theory-driven program designed to prevent cyberbullying and improve cyberbullying coping skills. It involves students, teachers, and families. During a 3-month period, external experts conducted eight training sessions with students, two with teachers and one with families. ConRed was evaluated through a quasi experimental design, in which students from three secondary schools were separated into experimental and control groups. The sample comprised 875 students, aged between 11 and 19 years. More students (n = 586) were allocated to the experimental groups at the specific insistence of the management of all schools; the remainder (n = 289) formed the control. Repeated measures MANOVA showed that cyber victims, cyber aggressors and cyberbully/victims reduced their involvement in cyberbullying. Moreover, cyber-victims and bystanders adjusted their perceptions about their control of personal information on the Internet, and cyber aggressors and bystanders reduced their Internet dependence. The ConRed program had stronger effects on male participants, especially in heightening their affective empathy. PMID- 26351133 TI - Numerical design and optimization of hydraulic resistance and wall shear stress inside pressure-driven microfluidic networks. AB - Microfluidic networks represent the milestone of microfluidic devices. Recent advancements in microfluidic technologies mandate complex designs where both hydraulic resistance and pressure drop across the microfluidic network are minimized, while wall shear stress is precisely mapped throughout the network. In this work, a combination of theoretical and modeling techniques is used to construct a microfluidic network that operates under minimum hydraulic resistance and minimum pressure drop while constraining wall shear stress throughout the network. The results show that in order to minimize the hydraulic resistance and pressure drop throughout the network while maintaining constant wall shear stress throughout the network, geometric and shape conditions related to the compactness and aspect ratio of the parent and daughter branches must be followed. Also, results suggest that while a "local" minimum hydraulic resistance can be achieved for a geometry with an arbitrary aspect ratio, a "global" minimum hydraulic resistance occurs only when the aspect ratio of that geometry is set to unity. Thus, it is concluded that square and equilateral triangular cross-sectional area microfluidic networks have the least resistance compared to all rectangular and isosceles triangular cross-sectional microfluidic networks, respectively. Precise control over wall shear stress through the bifurcations of the microfluidic network is demonstrated in this work. Three multi-generation microfluidic network designs are considered. In these three designs, wall shear stress in the microfluidic network is successfully kept constant, increased in the daughter branch direction, or decreased in the daughter-branch direction, respectively. For the multi-generation microfluidic network with constant wall shear stress, the design guidelines presented in this work result in identical profiles of wall shear stresses not only within a single generation but also through all the generations of the microfluidic network under investigation. The results obtained in this work are consistent with previously reported data and suitable for a wide range of lab-on-chip applications. PMID- 26351132 TI - A comparative study for the inactivation of multidrug resistance bacteria using dielectric barrier discharge and nano-second pulsed plasma. AB - Bacteria can be inactivated through various physical and chemical means, and these have always been the focus of extensive research. To further improve the methodology for these ends, two types of plasma systems were investigated: nano second pulsed plasma (NPP) as liquid discharge plasma and an Argon gas-feeding dielectric barrier discharge (Ar-DBD) as a form of surface plasma. To understand the sterilizing action of these two different plasma sources, we performed experiments with Staphylococcus aureus (S. aureus) bacteria (wild type) and multidrug resistant bacteria (Penicillum-resistant, Methicillin-resistant and Gentamicin-resistant). We observed that both plasma sources can inactivate both the wild type and multidrug-resistant bacteria to a good extent. Moreover, we observed a change in the surface morphology, gene expression and beta-lactamase activity. Furthermore, we used X-ray photoelectron spectroscopy to investigate the variation in functional groups (C-H/C-C, C-OH and C=O) of the peptidoglycan (PG) resulting from exposure to plasma species. To obtain atomic scale insight in the plasma-cell interactions and support our experimental observations, we have performed molecular dynamics simulations to study the effects of plasma species, such as OH, H2O2, O, O3, as well as O2 and H2O, on the dissociation/formation of above mentioned functional groups in PG. PMID- 26351134 TI - Unilateral and bilateral dental transpositions in the maxilla-dental and skeletal findings in 63 individuals. AB - AIM: This was to elucidate dental and skeletal findings in individuals with unilateral and bilateral maxillary dental transpositions. MATERIAL AND METHODS: The sample comprised of radiographic materials from 63 individuals with maxillary dental transpositions from the Departments of Odontology at the Universities of Copenhagen and Aarhus and by the Danish municipal orthodontic service. The cases were divided into three groups: unilateral transposition of the canine and first premolar (Type 1U), bilateral transposition of canine and first premolar (Type 1B), and unilateral transposition of canine and lateral incisor (Type 2). The dentitions were analysed regarding agenesis and dental morphological anomalies on panoramic radiographs, and craniofacial aspects were cephalometrically analysed on profile images The results were statistically evaluated. RESULTS: All groups demonstrated increased occurrences of agenesis (Type 1U and Type 1B: 31 agenesis in 15 patients; and Type 2 three agenesis in three patients). Taurodontic root morphology was most dominant in Type 1U. Peg-shaped lateral incisors showed an increased occurrence, though not in Type 1U. Skeletally, Type 1B and Type 1U demonstrated maxillary retrognathia (more pronounced in Type 1B). Type 2 showed a significant posterior inclination of the maxilla. CONCLUSION: Transpositions of maxillary canines involve dental and skeletal deviations. Dental deviations were predominantly taurodontic root morphology and agenesis. Regarding skeletal deviations, bilateral transpositions of the canines and the first premolars are associated with skeletal changes. Unilateral transpositions are possibly a localised deviation with minor or no skeletal involvements. The results indicate a possible difference in the aetiologies of unilateral and bilateral transpositions. PMID- 26351135 TI - Overcoming ABCG2-mediated drug resistance with imidazo-[1,2-b]-pyridazine-based Pim1 kinase inhibitors. AB - PURPOSE: Multidrug efflux pumps such as ABCG2 confer drug resistance to a number of cancer types, leading to poor prognosis and outcome. To date, the strategy of directly inhibiting multidrug efflux pumps in order to overcome drug resistance in cancer has been unsuccessful. An alternative strategy is to target proteins involved in the regulation of multidrug efflux pump activity or expression. Pim1 kinase has been demonstrated to phosphorylate ABCG2, promote its oligomerisation and contribute to its ability to confer drug resistance. METHODS: In the present manuscript, imidazo-pyridazine-based inhibitors of Pim1 were examined for their ability to overcome ABCG2-mediated drug resistance. Drug efficacy was measured as a cytotoxic response or an effect on transport by ABCG2. Protein expression patterns were assessed using western immuno-blotting. RESULTS: The two Pim1 inhibitors increased the potency of flavopiridol, mitoxantrone, topotecan and doxorubicin, specifically in ABCG2-expressing cells. This effect was associated with an increase in the cellular accumulation of [(3)H]-mitoxantrone, suggesting direct impairment of the transporter. However, prolonged pre-incubation with the studied inhibitors greatly enhanced the effect on mitoxantrone accumulation. The inhibitors caused a significant time-dependent reduction in the expression of ABCG2 in the resistant cells, an effect that would improve drug efficacy. CONCLUSION: Consequently, it appears that the Pim1 inhibitors display a dual-mode effect on ABCG2-expressing cancer cells. This may provide a powerful new strategy in overcoming drug resistance by targeting proteins that regulate expression of efflux pumps. PMID- 26351136 TI - Screening of HELQ in breast and ovarian cancer families. AB - Several high and moderate risk alleles have been identified for breast and ovarian cancer predisposition and most of them encode proteins that function in DNA repair. A prospective candidate for breast and ovarian cancer susceptibility is the HELQ helicase that has a role in the resolution of DNA interstrand cross links. HELQ interacts with the RAD51 paralog complex BCDX2. Two components of the complex, RAD51C and RAD51D, increase the risk of ovarian cancer especially, and the other two, RAD51B and XRCC2 have been associated with breast cancer risk. To investigate the role of HELQ in cancer predisposition, we screened the gene for germline variation in 185 Finnish breast or ovarian cancer families and performed haplotype analyses for 1517 breast cancer cases, 308 ovarian cancer cases, and 1234 population controls using five common polymorphisms at the HELQ gene locus. No truncating mutations were identified among the families. One putatively pathogenic missense mutation c.1309A>G was identified but no additional carriers were observed in the subsequent genotyping of 332 familial breast or ovarian cancer patients. Furthermore, the haplotype distribution did not differ between breast or ovarian cancer cases and population controls. Our results indicate that HELQ is not a major breast and ovarian cancer susceptibility gene in the Finnish population. However, we cannot rule out rare risk-variants in the Finnish or other populations and larger datasets are needed to further assess the role of HELQ especially in ovarian cancer predisposition. PMID- 26351137 TI - RGD-conjugated two-photon absorbing near-IR emitting fluorescent probes for tumor vasculature imaging. AB - Observation of the activation and inhibition of angiogenesis processes is important in the progression of cancer. Application of targeting peptides, such as a small peptide that contains adjacent L-arginine (R), glycine (G) and L aspartic acid (D) residues can afford high selectivity and deep penetration in vessel imaging. To facilitate deep tissue vasculature imaging, probes that can be excited via two-photon absorption (2PA) in the near-infrared (NIR) and subsequently emit in the NIR are essential. In this study, the enhancement of tissue image quality with RGD conjugates was investigated with new NIR-emitting pyranyl fluorophore derivatives in two-photon fluorescence microscopy. Linear and nonlinear photophysical properties of the new probes were comprehensively characterized; significantly the probes exhibited good 2PA over a broad spectral range from 700-1100 nm. Cell and tissue images were then acquired and examined, revealing deep penetration and high contrast with the new pyranyl RGD-conjugates up to 350 MUm in tumor tissue. PMID- 26351138 TI - Long-Range Transcriptional Control of the Il2 Gene by an Intergenic Enhancer. AB - Interleukin-2 (IL-2) is a potent cytokine with roles in both immunity and tolerance. Genetic studies in humans and mice demonstrate a role for Il2 in autoimmune disease susceptibility, and for decades the proximal Il2 upstream regulatory region has served as a paradigm of tissue-specific, inducible gene regulation. In this study, we have identified a novel long-range enhancer of the Il2 gene located 83 kb upstream of the transcription start site. This element can potently enhance Il2 transcription in recombinant reporter assays in vitro, and the native region undergoes chromatin remodeling, transcribes a bidirectional enhancer RNA, and loops to physically interact with the Il2 gene in vivo in a CD28-dependent manner in CD4(+) T cells. This cis regulatory element is evolutionarily conserved and is situated near a human single-nucleotide polymorphism (SNP) associated with multiple autoimmune disorders. These results indicate that the regulatory architecture of the Il2 locus is more complex than previously appreciated and suggest a novel molecular basis for the genetic association of Il2 polymorphism with autoimmune disease. PMID- 26351139 TI - The Stationary-Phase Cells of Saccharomyces cerevisiae Display Dynamic Actin Filaments Required for Processes Extending Chronological Life Span. AB - Stationary-growth-phase Saccharomyces cerevisiae yeast cultures consist of nondividing cells that undergo chronological aging. For their successful survival, the turnover of proteins and organelles, ensured by autophagy and the activation of mitochondria, is performed. Some of these processes are engaged in by the actin cytoskeleton. In S. cerevisiae stationary-phase cells, F actin has been shown to form static aggregates named actin bodies, subsequently cited to be markers of quiescence. Our in vivo analyses revealed that stationary-phase cultures contain cells with dynamic actin filaments, besides the cells with static actin bodies. The cells with dynamic actin displayed active endocytosis and autophagy and well-developed mitochondrial networks. Even more, stationary phase cell cultures grown under calorie restriction predominantly contained cells with actin cables, confirming that the presence of actin cables is linked to successful adaptation to stationary phase. Cells with actin bodies were inactive in endocytosis and autophagy and displayed aberrations in mitochondrial networks. Notably, cells of the respiratory activity-deficient cox4Delta strain displayed the same mitochondrial aberrations and actin bodies only. Additionally, our results indicate that mitochondrial dysfunction precedes the formation of actin bodies and the appearance of actin bodies corresponds to decreased cell fitness. We conclude that the F-actin status reflects the extent of damage that arises from exponential growth. PMID- 26351142 TI - Non-hormonal management of menopausal vasomotor symptoms: Psychosocial interventions. PMID- 26351140 TI - AMPK Promotes Aberrant PGC1beta Expression To Support Human Colon Tumor Cell Survival. AB - A major goal of cancer research is the identification of tumor-specific vulnerabilities that can be exploited for the development of therapies that are selectively toxic to the tumor. We show here that the transcriptional coactivators peroxisome proliferator-activated receptor gamma coactivator 1beta (PGC1beta) and estrogen-related receptor alpha (ERRalpha) are aberrantly expressed in human colon cell lines and tumors. With kinase suppressor of Ras 1 (KSR1) depletion as a reference standard, we used functional signature ontology (FUSION) analysis to identify the gamma1 subunit of AMP-activated protein kinase (AMPK) as an essential contributor to PGC1beta expression and colon tumor cell survival. Subsequent analysis revealed that a subunit composition of AMPK (alpha2beta2gamma1) is preferred for colorectal cancer cell survival, at least in part, by stabilizing the tumor-specific expression of PGC1beta. In contrast, PGC1beta and ERRalpha are not detectable in nontransformed human colon epithelial cells, and depletion of the AMPKgamma1 subunit has no effect on their viability. These data indicate that Ras oncogenesis relies on the aberrant activation of a PGC1beta-dependent transcriptional pathway via a specific AMPK isoform. PMID- 26351143 TI - Premenstrual syndrome: A mini review. AB - Premenstrual syndrome (PMS) is characterized by recurrent, moderate-to-severe affective, physical, and behavioral symptoms that develop during the luteal menstrual cycle and disappear within a few days of menstruation. Premenstrual dysphoric disorder (PMDD) is a severe and disabling condition that can affect personal relationships and occupational activities. PMS occurs in 30-40% of reproductive-age females; PMDD affects 3-8% of this population. Although the etiology of PMS is unclear, several theories suggest increased sensitivity to normal hormonal changes and neurotransmitter abnormalities. The diagnostic method of PMS is the Daily Record of Severity of Problems, which women with PMS can use to self-report several symptoms and their severity. Although combined oral contraceptives and serotonergic antidepressants are effective drugs, each is a different option for treating PMS/PMDD. Serotonergic antidepressants are the drugs of choice for improving both physical and mood symptoms. Combined oral contraceptives appear to primarily improve physical symptoms. Clinicians should consider each patient's situation individually. Other treatment options include lifestyle modification, cognitive behavioral therapy, and herbal medicine (e.g., chasteberry). PMID- 26351144 TI - EMAS position statement: Non-hormonal management of menopausal vasomotor symptoms. PMID- 26351141 TI - Isocyanates and work-related asthma: Findings from California, Massachusetts, Michigan, and New Jersey, 1993-2008. AB - BACKGROUND: Isocyanates remain a leading cause of work-related asthma (WRA). METHODS: Two independent data systems were analyzed for the period 1993-2008: (1) State-based WRA case surveillance data on persons with isocyanate-induced WRA from four states, and (2) Occupational Safety and Health Administration (OSHA) Integrated Management Information System (IMIS) isocyanate air sampling results. RESULTS: We identified 368 cases of isocyanate-induced WRA from 32 industries and 678 OSHA isocyanate air samples with detectable levels from 31 industries. Seventeen industries were unique to one or the other dataset. CONCLUSION: Isocyanate-induced WRA continues to occur in a wide variety of industries. Two data systems uncovered industries with isocyanate exposures and/or illness. Improved control measures and standards, including medical surveillance, are needed. More emphasis is needed on task-specific guidance, spill clean-up procedures, skin and respiratory protection, and targeted medical monitoring to mitigate the hazards of isocyanate use. PMID- 26351145 TI - CD5 as a Target for Immune-Based Therapies. AB - CD5 was one of the first surface receptors described for mouse and human T lymphocytes. Since then, it has been found to be highly expressed by regulatory T cells and a subpopulation of regulatory B cells, to be physically associated with the T- and B-cell antigen receptors, to negatively modulate TCR- and BCR-mediated signals, and to bind certain pathogen-associated molecular patterns. These findings position CD5 as an attractive target for developing immunotherapies aimed at either boosting or dampening ongoing immune responses. Here the available data on the function of CD5 and its involvement in the regulation of immune responses in health and disease are reviewed, as well as the evidence for and future challenges in developing therapeutic strategies aimed at targeting CD5 for autoimmune diseases, cancer, and infections. PMID- 26351146 TI - The Link between Psychological Stress and Autoimmune Response in Children. AB - Stress is defined as a state of threatened homeostasis or disharmony that is counteracted by a complex repertoire of physiological and behavioral adaptive responses in order to establish homeostasis. Confronted with a stressful condition, the nervous and immune systems initiate a coping process to maintain homeostasis in the body. Psychological stress, recognized as a public health issue in children and young adults, may be one mechanism to induce and maintain autoimmunity in children. It is necessary to increase our understanding of how psychological stress can affect the immune system at a young age because autoimmune diseases, especially type 1 diabetes, are alarmingly common in children. Psychological stress may be involved in other autoimmune diseases, such as celiac disease, systemic lupus erythematosus, and juvenile idiopathic arthritis, that frequently occur in children as well. This review summarizes the studies attempting to evaluate the link between psychological stress and autoimmune response in children. A number of them have observed that the autoimmune disease itself causes psychological stress. We are far from fully understanding how long-term psychological stress is linked to autoimmune response in children with a high risk of, or already diagnosed, autoimmune disease. PMID- 26351149 TI - Expression patterns of genes encoding plasma membrane aquaporins during fruit development in cucumber (Cucumis sativus L.). AB - Aquaporins are membrane channels precisely regulating water movement through cell membranes in most living organisms. Despite the advances in the physiology of fruit development, their participation during fruit development in cucumber still barely understood. In this paper, the expressions of 12 genes encoding plasma membrane intrinsic proteins (PIPs) were analyzed during cucumber fruit development in our work. Based on the homology search with known PIPs from rice, Arabidopsis and strawberry, 12 cucumber PIP genes subfamily members were identified. Cellular localization assays indicated that CsPIPs were localized in the plasma membrane. The qRT-PCR analysis of CsPIPs showed that 12 CsPIPs were differentially expressed during fruit development. These results suggest that 12 genes encoding plasma membrane intrinsic proteins (CsPIPs) play very important roles in cucumber life cycle and the data generated will be helpful in understanding their precise roles during fruit development in cucumber. PMID- 26351147 TI - Mechanisms of Cholera Toxin in the Modulation of TH17 Responses. AB - Numerous studies have shown that TH17 cells and their signature cytokine IL-17A are critical to host defense against various bacterial and fungal infections. The protective responses mediated by TH17 cells and IL-17A include the recruitment of neutrophils, release of antimicrobial peptides and chemokines, and enhanced tight junction of epithelial cells. Due to the importance of TH17 cells in infections, efforts have been made to develop TH17-based vaccines. The goal of vaccination is to establish a protective immunological memory. Most currently approved vaccines are antibody-based and have limited protection against stereotypically different strains. Studies show that T-cell-based vaccines may overcome this limitation and protect hosts against infection of different strains. Two main strategies are used to develop TH17 vaccines: identification of TH17-specific antigens and TH17 skewing adjuvants. Studies have revealed that cholera toxin (CT) induces a potent Th17 response following vaccination. Antigen vaccination along with CT induces a robust TH17 response, which is sometimes accompanied by TH1 responses. Due to the toxicity of CT, it is hard to apply CT in a clinical setting. Thus, understanding how CT modulates TH17 responses may lead to the development of successful TH17 based vaccines. PMID- 26351150 TI - Biochemical characterization of embryogenic calli of Vanilla planifolia in response to two years of thidiazuron treatment. AB - Vanilla planifolia embryogenic calli were cultured for two years on a medium containing thidiazuron (TDZ). Due to the presence of TDZ, these calli were under permanent chemical treatment and the differentiation of adventitious shoots from protocorm-like-bodies (PLBs) was blocked. When embryogenic calli were transferred onto a medium without TDZ, shoot organogenesis and plantlet regeneration occurred. To gain better knowledge about the biochemical and molecular processes involved in the morphoregulatory role of TDZ, hormonal and metabolomic analyses were performed. Our results indicate that in the presence of TDZ, embryogenic calli contained a high amount of abscisic acid (ABA) essentially metabolized into abscisic acid glucosyl ester (ABAGE) and phaseic acid (PA), which was the most abundant. When transferred onto a medium without TDZ, shoot regeneration and development take place in four stages that include: embryogenic calli growth, differentiation of PLBs from meristmatic cells zones (MCZ), shoot organogenesis from PLBs and the elongation of well-formed shoots. From a hormonal perspective, the significant reduction in ABA metabolism and its readjustment in the ABAGE pathway triggered PLBs formation. However, this first morphogenesis was stimulated by a strong reduction in IAA metabolism. The organogenesis of PLBs into shoots is associated with an increase in ABA catabolism and a gradual shift in cellular metabolism towards shoot differentiation. Thus, the initiation of the elongation process in shoots is correlated with an alteration in metabolite composition, including an increase in energy reserves (sucrose/starch) and a rapid decrease in alanine content. Our data highlighted the relationship between endogenous hormone signalling, carbohydrate metabolism and shoot organogenesis in Orchid plants. PMID- 26351148 TI - CD8+ T Cell-Independent Immune-Mediated Mechanisms of Anti-Tumor Activity. AB - Despite the growing number of preclinical and clinical trials focused on immunotherapy for the treatment of malignant gliomas, the prognosis for this disease remains grim. Cancer immunotherapy seeks to recruit an effective immune response to eliminate tumor cells. To date, cancer vaccines have shown only limited effectiveness because of our incomplete understanding of the necessary effector cells and mechanisms that yield efficient tumor clearance. CD8+ T cell cytotoxic activity has long been proposed as the primary effector function necessary for tumor regression. However, there is increasing evidence that indicates that components of the immune system other than CD8+ T cells play important roles in tumor eradication and control. The following review should provide an understanding of the mechanisms involved in an effective antitumor response to guide future therapeutic designs. The information provided suggests an alternate means of effective tumor clearance in malignant glioma to the canonical CD8+ cytotoxic T cell mechanism. PMID- 26351151 TI - Increasing the stearate content in seed oil of Brassica juncea by heterologous expression of MlFatB affects lipid content and germination frequency of transgenic seeds. AB - Fatty acids from dietary lipids can impart both beneficial and harmful health effects. The compositional balance between saturated and unsaturated fatty acids plays a decisive role in maintaining the physiological harmony, proper growth and development in the human system. In case of Brassica juncea seed oil, the level of saturated fatty acid, especially desirable stearate is very much lower than the recommended value, along with a high content of nutritionally undesirable erucic acid. Therefore, in order to shift the carbon flux towards the production of stearate at the expense of erucate, the MlFatB gene encoding a FatB thioesterase from Madhuca longifolia (latifolia) was expressed heterologously in seed tissues of B. juncea. The functional MlFatB competed with the highly active endogenous BjFatA thioesterase, and the transgenic B. juncea lines showed noteworthy changes in their seed fatty acid profiles. The proportion of stearate increased up to 16-fold, constituting almost 31% of the total fatty acids along with the production of arachidic acid in significant amount (up to ~11%). Moreover, the content of erucate was reduced up to 71% in the seed oils of transgenic lines. Although a nutritionally desirable fatty acid profile was achieved, the transgenic seeds exhibit reduction or abolition of seed germination in addition to a decrease in seed lipid content. The findings of the present study revealing the stearoyl-ACP thioesterase-mediated enhancement of the stearate content that is associated with reduced germination frequency of transgenic B. juncea seeds, may explain why no natural or induced stearate-rich Brassica has been found or developed. Furthermore, this study also suggests that the newly characterized MlFatB is a potential candidate gene for refined metabolic engineering strategy in B. juncea or other plant species for increasing stearate content in seed oil. PMID- 26351152 TI - The effect of tumor location on oncologic outcomes in patients with upper urinary tract urothelial carcinoma stratified by pathologic stage. AB - OBJECTIVES: The aim of this study was to investigate the effect of tumor location on oncologic outcomes in patients with upper urinary tract urothelial carcinoma (UTUC) stratified according to pathologic stage. MATERIAL AND METHODS: Between January 1996 and March 2009, 503 patients with UTUC were enrolled who had undergone radical nephroureterectomies and had no nodal or distal metastases. Preoperative chemotherapy or radiation therapy was not administered to any study patient. Clinicopathologic patient characteristics were obtained and used to analyze recurrence-free survival (RFS), cancer-specific survival, and overall survival with the Cox proportional hazards model. RESULTS: During the median follow-up of 52 months, patients with pathologic tumor (pT) stage 3 ureteral tumors had a shorter duration of RFS compared with those with pT3 renal pelvis tumors (5-y RFS: 50% and 71%, P = 0.047). There was no prognostic relevance to the tumor location in pTa/Tis/T1 and pT2 diseases. RFS and cancer-specific survival were significantly shorter in duration in pT3 ureteral disease compared with pT2 diseases (P<0.001 and P = 0.028). No differences were found in oncologic outcomes between pT3 renal pelvic and pT2 diseases. The presence of pT3 ureteral tumors actually increased the risks of disease recurrence (hazard ratio [HR] = 7.82, P<0.001), cancer-specific death (HR = 5.08, P<0.001), and overall mortality (HR = 3.25, P = 0.031). CONCLUSIONS: Patients with UTUC and pT3 ureteral tumors had an increased risk of disease recurrence and cancer-specific death. These results underscore the need for close follow-up and the consideration of adjuvant chemotherapy for patients with pT3 ureteral cancer. PMID- 26351153 TI - Overview and management of toxicities associated with systemic therapies for advanced renal cell carcinoma. AB - The advent of novel targeted agents for metastatic renal cell carcinoma (RCC) has offered clinical benefits over traditional immunotherapy (e.g., interleukin-2 and interferon-alpha) in both efficacy and safety profiles. The major classes of these targeted therapies for metastatic RCC include the tyrosine-kinase inhibitors, monoclonal antibody against vascular endothelial growth factor, and inhibitors of the mammalian target of rapamycin. Most recently, the success of immune checkpoint inhibitors--notably antibodies directed against programmed death-1 and its ligand--has also been demonstrated in RCC. With such progress in therapy, early detection, and subsequent management of treatment-related adverse events allow for patients to remain on active therapy for as long as possible and also enhance the probability of patients tolerating subsequent second line options. However, despite such impressive gains in efficacy with these new agents, therapeutic progress are primarily palliative in nature--hence, the critical importance of minimizing discomfort and potential harm in this patient population cannot be understated. PMID- 26351154 TI - The Biopsychosocialspiritual Impact of Chronic Pain, Chronic Illness, and Physical Disabilities in Adolescence. AB - The effects of chronic pain, chronic illness, and physical disability in adolescence are diverse, often influencing every facet of an adolescent's life. The biopsychosocialspiritual model provides a framework within which to conceptualize the experience of the adolescent with chronic pain and can be very helpful in guiding clinical care including creating comprehensive interdisciplinary treatment plans. Literature on chronic pain often focuses on pediatric or adult populations and does not lend information on how to provide evidence-based treatment for the adolescent in chronic pain. The study of chronic pain in adolescence has been largely limited by small samples, cross-sectional and observational designs, and studies that intertwine findings with pediatric and adult populations. Herein, we review the literature on the biopsychosocialspiritual experience of the adolescent with chronic pain. PMID- 26351155 TI - Evaluation of dental enamel caries assessment using Quantitative Light Induced Fluorescence and Optical Coherence Tomography. AB - An in vitro study of morphological alterations between sound dental structure and artificially induced white spot lesions in human teeth, was performed through the loss of fluorescence by Quantitative Light-Induced Fluorescence (QLF) and the alterations of the light attenuation coefficient by Optical Coherence Tomography (OCT). To analyze the OCT images using a commercially available system, a special algorithm was applied, whereas the QLF images were analyzed using the software available in the commercial system employed. When analyzing the sound region against white spot lesions region by QLF, a reduction in the fluorescence intensity was observed, whilst an increase of light attenuation by the OCT system occurred. Comparison of the percentage of alteration between optical properties of sound and artificial enamel caries regions showed that OCT processed images through the attenuation of light enhanced the tooth optical alterations more than fluorescence detected by QLF System. QLF versus OCT imaging of enamel caries: a photonics assessment. PMID- 26351156 TI - Long-Term Outcome of Open Plantar Fascia Release. AB - BACKGROUND: Plantar fasciitis is thought to be a self-limiting condition best treated by conservative measures, but despite this many patients have a prolonged duration of symptoms and surgery may be indicated. Partial plantar fascial release is reported to have a short-term success rate of up to 80%, but anecdotally this was not thought to represent our local experience. METHODS: An audit of long-term patient-reported outcomes following open partial plantar fascia release was performed. A total of 30 patients (33 feet) were identified over a 10-year period and case notes were reviewed. Patients were contacted by letter and invited to complete 2 validated patient-reported outcome score questionnaires (Visual Analog Scale-Foot and Ankle [VAS-FA] and Manchester Oxford Foot Questionnaire [MOXFQ]). Responses were received from 24 patients (26 feet). The average ages were 42.4 (range 24-61) for male and 46.2 (range 33-60) for female patients, with a female/male ratio of 2.7:1. The average duration of treatment prior to operative intervention was 3.1 years (range 1-5). Preoperatively, our cohort underwent a range of conservative measures. All patients were reviewed postoperatively, and average time from surgery to completion of questionnaires was 80 months (range 14-130). RESULTS: The outcomes were worse in patients who had received preoperative steroid injections and this was found to be statistically significant. The mean MOXFQ score was 33.6 +/- 3.9 (0-64). Mean VAS-FA score was 57.8 +/- 4.9 (24-100). CONCLUSION: This study found a negative correlation between duration of follow-up and outcome, in both MOXFQ and VAS-FA, showing that patients continued to improve many years postoperatively. The authors also found worse outcomes with preoperative steroid injections, better outcomes in older patients, and a weak gender bias, suggesting results in men were better than those in women. A prolonged recovery period and generally poor outcomes leads the authors to suggest that open plantar fascia release is of questionable clinical value and that patients may improve in the natural course of the disease, in spite of surgery. LEVEL OF EVIDENCE: Level III, comparative study. PMID- 26351157 TI - Tendoscopic Repair of the Superior Peroneal Retinaculum via 2 Portals for Peroneal Tendon Instability. PMID- 26351158 TI - Results of Arthroscopic Subtalar Arthrodesis for Adult-Acquired Flatfoot Deformity vs Posttraumatic Arthritis. AB - BACKGROUND: The goal of this study was to compare results with arthroscopic posterior subtalar arthrodesis between patients treated for adult-acquired flatfoot deformity (AAFD) due to posterior tibial tendon dysfunction and patients with posttraumatic subtalar arthritis. METHODS: Retrospective case series of 61 consecutive patients (group 1: posttraumatic arthritis, n = 37; group 2: AAFD, n = 24) averaging 49 years of age (range, 21-72 years) undergoing posterior arthroscopic subtalar arthrodesis via 1 or 2 percutaneous 6.5- to 7.3-mm screws, with a mean follow-up of 57.5 months (range, 24-105 months). Fusion was defined as the appearance of bony trabeculae across the subtalar joint on standard x rays, along with clinical signs of union. RESULTS: Patients with posttraumatic arthritis (group 1) were more predominantly male and younger than patients treated for AAFD (group 2). Overall, we achieved a 95.1% radiologic union rate after an average of 11.7 weeks. Complications appeared in 14.8% of patients. Union rate and complications did not differ significantly between groups. American Orthopaedic Foot & Ankle Society (AOFAS) scores improved significantly for both patient groups, although patients with AAFD showed significantly larger improvement and higher postoperative AOFAS scores, even after adjusting for age and sex (mean improvement in AOFAS scores: 27.0 +/- 9.1 points for the posttraumatic arthritis group vs 34.9 +/- 7.4 points for the AAFD group; P < .001). CONCLUSIONS: Arthroscopic subtalar arthrodesis was a safe and reliable technique, with consistent improvement in AOFAS scores throughout different patient subgroups, as well as comparable time to union and complication rates. Improvements were larger for patients treated for AAFD, even after adjusting for age and sex. LEVEL OF EVIDENCE: Level III, retrospective case series. PMID- 26351159 TI - Comparison of 2D-3D Measurements of Hallux and First Ray Sagittal Motion in Patients With and Without Hallux Valgus. AB - BACKGROUND: Clinicians base treatment decisions on measures of hallux and first ray motion in the management of first metatarsophalangeal joint disorders. Women account for a majority of the patients. This study assessed the reliability of a 2D approach for the measurements of sagittal motion, and compared the result to a Cardan (3D) angle criterion standard and evaluated how hallux valgus (bunion) deformity affected the comparisons. METHODS: Twenty-nine women (controls n = 10; bunion n = 19) were examined using a retrospective repeated measures design. Weightbearing magnetic resonance (MR) images were acquired to replicate the position of the foot during the stance phase of gait. The images were reconstructed into virtual bone models using computer processes, whereby measures of hallux and first ray motion were represented by 2D and 3D methods of measurement. An examiner measured 2D motion on the image data sets using a goniometer, and reliability was assessed. The 3D Cardan angle result was derived from a matrix calculation. The 2D-3D comparison of measurements was evaluated with an analysis of variance (ANOVA) model across gait conditions, run separate for groups. RESULTS: The 2D measurement was reliable (ICC >= 0.98, SEM <= 0.89 degrees). There was no method-by-condition interaction (F <= 1.37, P >= .25) between variables. No significant difference was detected between the 2D-3D measurements in the control group (F <= 1.24, P >= .30), but the measurements were statistically different (F >= 4.46, P <= .049) in the bunion group. CONCLUSION: This study described a reliable 2D approach for measuring hallux and first ray sagittal motion from weightbearing images. The 2D measurements were comparable to a Cardan angle component motion result in controls, but not in women with bunion. CLINICAL RELEVANCE: Joint motion measurements may augment clinical decision making. These results suggest that a 2D image-based approach may be adequate to estimate hallux and first ray sagittal motion, although bunion deformity creates out-of-plane motions that may require 3D methods to accurately quantify. Further clinical study is required to assess the differences in clinical outcomes between measurement techniques. PMID- 26351160 TI - Bullying victimisation and paranoid ideation in people at ultra high risk for psychosis. AB - BACKGROUND: Bullying victimisation has been suggested to contribute to paranoid ideation in general population samples and recent evidence found that individuals with an ultra high risk (UHR) for psychosis are twice as likely to have been bullied than controls. AIMS: This study sought to examine whether a history of bullying would be associated with higher levels of paranoid ideation in individuals with an UHR and in healthy controls (HCs). METHOD: The study included 64 UHR and 43 HC participants. Following the baseline assessment, participants entered a Virtual Reality (VR) London Underground train. Paranoid ideation was measured immediately after the end of the VR experience. RESULTS: Compared to HCs, UHR participants described higher levels of childhood bullying (OR 5.19, 95% CI=2.21-12.19, p<.001) and experienced more paranoid ideation during VR (chi(2)(1)=21.06, p<.001). Childhood bullying was associated with paranoid ideation during VR in both groups (chi(2)(1)=5.931, p=,021) but prolonged exposure to bullying was not associated with increased paranoid ideation. CONCLUSION: A history of bullying in childhood is particularly common in young adults at high risk for psychosis. However bullying is associated with paranoid ideation in later life, independent of clinical status, consistent with dimensional models of psychotic phenomena. PMID- 26351161 TI - Compression Effects on the Phase Behaviour of Miconazole-Poly (1-Vinylpyrrolidone Co-Vinyl Acetate) Solid Dispersions-Role of Pressure, Dwell Time, and Preparation Method. AB - Compression of miconazole-poly (1-vinylpyrrolidone-co-vinyl acetate) (PVPVA64) solid dispersions prepared by spray drying and hot-melt extrusion was performed to gain insights into effect of compression pressure, dwell time, and preparation method on compression-dependent phase behavior. The solid dispersions prepared by spray drying were initially phase-separated showing two glass transition temperature (Tg), whereas the extruded samples showed one single Tg indicating better mixing. Compression caused mixing of spray-dried solid dispersions at high compression pressures and especially high dwell times. The extruded systems showed no statistically significant differences. However, physical mixtures made up from extruded samples containing 20% and 40% of active pharmaceutical ingredient underwent mixing upon compression. Coincidence Doppler measurements were performed to quantify the free volume of PVPVA64 which is a major contributor to the free volume in the solid dispersion matrix. A small but significant difference was found between the open free volume of the pure polymer subjected to varied manufacturing processes. Compression-induced plastic deformation and plastic flow enhances molecular mobility leading to mixing of different domains in solid dispersions. Different manufacturing methods may result in products with similar free volume, thereby showing similar molecular mobility. PMID- 26351162 TI - [Post-translational modification (PTM) bioinformatics in China: progresses and perspectives]. AB - Post-translational modifications (PTMs) are essential for regulating conformational changes, activities and functions of proteins, and are involved in almost all cellular pathways and processes. Identification of protein PTMs is the basis for understanding cellular and molecular mechanisms. In contrast with labor intensive and time-consuming experiments, the PTM prediction using various bioinformatics approaches can provide accurate, convenient, and efficient strategies and generate valuable information for further experimental consideration. In this review, we summarize the current progresses made by Chineses bioinformaticians in the field of PTM Bioinformatics, including the design and improvement of computational algorithms for predicting PTM substrates and sites, design and maintenance of online and offline tools, establishment of PTM-related databases and resources, and bioinformatics analysis of PTM proteomics data. Through comparing similar studies in China and other countries, we demonstrate both advantages and limitations of current PTM bioinformatics as well as perspectives for future studies in China. PMID- 26351163 TI - [Application of next-generation semiconductor sequencing technologies in genetic diagnosis of inherited cardiomyopathies]. AB - Inherited cardiomyopathy is the most common hereditary cardiac disease. It also causes a significant proportion of sudden cardiac deaths in young adults and athletes. So far, approximately one hundred genes have been reported to be involved in cardiomyopathies through different mechanisms. Therefore, the identification of the genetic basis and disease mechanisms of cardiomyopathies are important for establishing a clinical diagnosis and genetic testing. Next generation semiconductor sequencing (NGSS) technology platform is a high throughput sequencer capable of analyzing clinically derived genomes with high productivity, sensitivity and specificity. It was launched in 2010 by Life Technologies of USA, and it is based on a high density semiconductor chip, which was covered with tens of thousands of wells. NGSS has been successfully used in candidate gene mutation screening to identify hereditary disease. In this review, we summarize these genetic variations, challenge and application of NGSS in inherited cardiomyopathy, and its value in disease diagnosis, prevention and treatment. PMID- 26351164 TI - [Research in metagenomics and its applications in translational medicine]. AB - Humans are born with microbiota, which have accompanied us through our life-span. There is an important symbiotic relationship between us and the microbial communities, thus microbial communities are of great importance to our health. All genomic information within this microbiota is referered to as "metagenomics" (also referred to as "human's second genome"). The analysis of high throughput metagenomic data generated from biomedical experiments would provide new approaches for translational research, and it have several applications in clinics. With the help of next generation sequencing technology and the emerging metagenomic approach (analysis of all genomic information in microbiota as a whole), we can overcome the pitfalls of tedious traditional method of isolation and cultivation of single microbial species. The metagenomic approach can also help us to analyze the whole microbial community efficiently and offer deep insights in human-microbe relationships as well as new ideas on many biomedical problems. In this review, we summarize frontiers in metagenomic research, including new concepts and methods. Then, we focus on the applications of metagenomic research in medical researches and clinical applications in recent years, which would clearly show the importance of metagenomic research in the field of translational medicine. PMID- 26351165 TI - [Identification of disease targets for precision medicine by integrative analysis of multi-omics data]. AB - With the development and improvement of high-throughput sequencing technologies, the acquisition and processing approaches of various biological omics data on different levels are becoming more mature. Despite several new disease-associated factors have been discovered based on single omics data analysis, identification of disease targets by integrative analysis of multi-omics data is still growing. Since life is a complex regulatory system in which the regulation of gene mutations, epigenetic alterations, abnormal gene expression as well as anomalous variations in signal pathway are related with the occurrence and development of diseases, it is obvious that finding therapeutic factors using single omics data analysis has its limitation. Systematical studies of clinical and pathological mechanisms and identification of optimal therapeutic targets through integrative analysis of multi-omics data from different levels and resources have become an important research direction of precision medicine, which would provide innovative perspectives on disease study and new theoretical basis for early diagnosis, personalized treatment and medicine guide. In this review, we introduce new technologies and research progresses in screening therapeutic targets using systematic omics such as genomics, transcriptomics and epigenomics, and also discusse new strategies and advantages of integrative analysis among them. PMID- 26351166 TI - [Phenotype predictions of the pathogenic nonsynonymous single nucleotide polymorphisms in deafness-causing gene COCH]. AB - The COCH (Coagulation factor C homology) gene, located in human chromosome 14q12 q13, is the first gene identified to cause vestibular dysfunction. COCH encodes cochlin, which contains an N-terminal LCCL (Limulus factor C, cochlin, and late gestation lung protein Lgl1) domain and a C-temimal vWFA (Von Willebrand factor type A) domain. Recently, functional research of COCH mutations and cochlin have come under the spotlight in the field of hereditary deafness. Approximately 16 mutations in COCH have been confirmed to date, among which 13 non-synonymous single nucleotide polymorphisms (nsSNPs) are the most common form of genetic variations. Nonetheless, there is poor knowledge on the relationship between the genotype and the phenotype of the other nsSNPs in COCH. Here we analyzed deleterious nsSNPs from all SNPs in the COCH gene in the vWFA domain based on different computational methods and identified eight potential pathogenic nsSNPs (I176T, R180Q, G265E, V269L, I368N, I372T, R416C and Y424D) after combining literatures with 3D structures. Meanwhile, the protein structures of six reported pathogenic nsSNPs (P51S, G87W, I109N, I109T, W117R and F121S) in the LCCL domain have been constructed, and we identified aberrant structural changes in loops and chains. The prediction of pathogenic mutations for COCH nsSNPs will provide a blueprint for screening pathogenic mutations, and it will be beneficial to the functional research of COCH and cochlin in this field. PMID- 26351167 TI - [Molecular networks and mechanisms of epithelial-mesenchymal transition regulated by miRNAs in the malignant melanoma cell line]. AB - Melanoma is a malignant cutaneous cancer of high metastasis and lethal rates. Epithelial-mesenchymal transition (EMT) plays an important role in the embryonic developmental process that is often activated during tumorigenesis and metastasis. In this study, we integrated of mRNA and miRNA transcriptome sequencing data of melanocyte and melanoma cell lines to identify genes involved in the process of tumor EMT in the first place, and uncovered 11 miRNAs including miR-130a-3p, miR-130b-3p, miR-125a-5p, miR-30a-3p, miR-195-5p, miR-345-5p, miR 509-3-5p, miR-374a-5p, miR-509-5p, miR-148a-3p and miR-330-3p, negatively related with EMT genes using the Mirsystem software. Bioinformatics analysis with target genes of these miRNAs revealed two networks closely related with cellular development and cell-to-cell interactions, as well as multiple signaling pathways participating in EMT. Validation of the 11 miRNAs with molecular biology experiments demonstrated that four miRNAs regulated oncogenes in melanomas, including miR-195-5p, miR-130a-3p, miR-509-5p, and miR-509-3-5p. Our study integrates two kinds of omics data to screen for EMT-related miRNAs, providing a new research idea in the precision genomics of cancer research. PMID- 26351168 TI - [Genetic variability and phylogenetic analysis of 39 short tandem repeat loci in Beijing Han population]. AB - In this study, we studied the genetic polymorphisms of short tandem repeat (STR) loci from 13 CODIS and 26 non-CODIS system in Beijing Han population for the first time, and established a database of 39 STR loci whose forensic parameters were further evaluated. Our results demonstrated no significant deviation from the Hardy-Weinberg equilibrium of 39 STR loci and no pairwise linkage disequilibrium between them. The power of discriminations, expected heterozygosity, polymorphic information content, and power of exclusion of 39 STR loci ranged from 0.7740-0.9818, 0.6000-0.9350, 0.5317-0.9047 and 0.2909-0.8673. The cumulated discrimination power and cumulative probability of exclusion were 0.999999999999999999999999999999999999999964971 and 0.999999999973878, respectively. Moreover, the genetic distance was calculated based on allele frequency and phylogenetic tree was built using STR loci data from Beijing Han and other 11 Chinese ethnic groups.This study provides important basic data for Chinese forensic DNA database and population genetics database, and has important significance in carrying out forensic individual identification, paternity testing, and population genetic study. PMID- 26351169 TI - [Genome-wide analysis of the LPAAT gene family in Gossypium raimondii and G. arboreum, and expression analysis of its orthologs in G. hirsutum]. AB - Lysophosphatidic acid acyltransferase (LPAAT) which converts lysophosphatidic acid into phosphatidic acid is a key enzyme in biosynthesis pathway of lipid in plants. In this study, we identified 17 members of the LPAAT gene family from genomic data of G. raimondii-D5 and G. arboreum-A2. Analysis of gene structure, chromosome distribution and phylogenetic evolution of LPAAT genes in diploid Gossypium using bioinformatics approaches showed that these genes can be divided into distinct subfamilies based on the distance of their genetic relationship. Moreover, the gene structures were similar within LPAAT subfamily members. The amino acid sequences encoded by LPAAT family genes contained three conserved motifs, including PhiFPEGTR-G binding site and Phi-NHQS- PhiDPhiPhi catalytic site. Phylogenetic analysis of LPAAT gene family demonstrated significant differences in evolution of LPAAT in different species. Finally, expression analysis of G. hirsutum ovules in different stages from RNA-seq and qRT-PCR data indicated that LPAAT gene may play a positive role in oil accumulation. Our studies facilitate understanding of the function of LPAAT gene family in Gossypium and selecting better LPAAT genes for further functional validation. PMID- 26351170 TI - [Construction and application of bioinformatic analysis platform for aquatic pathogen based on the MilkyWay-2 supercomputer]. AB - As a key component of life science, bioinformatics has been widely applied in genomics, transcriptomics, and proteomics. However, the requirement of high performance computers rather than common personal computers for constructing a bioinformatics platform significantly limited the application of bioinformatics in aquatic science. In this study, we constructed a bioinformatic analysis platform for aquatic pathogen based on the MilkyWay-2 supercomputer. The platform consisted of three functional modules, including genomic and transcriptomic sequencing data analysis, protein structure prediction, and molecular dynamics simulations. To validate the practicability of the platform, we performed bioinformatic analysis on aquatic pathogenic organisms. For example, genes of Flavobacterium johnsoniae M168 were identified and annotated via Blast searches, GO and InterPro annotations. Protein structural models for five small segments of grass carp reovirus HZ-08 were constructed by homology modeling. Molecular dynamics simulations were performed on out membrane protein A of Aeromonas hydrophila, and the changes of system temperature, total energy, root mean square deviation and conformation of the loops during equilibration were also observed. These results showed that the bioinformatic analysis platform for aquatic pathogen has been successfully built on the MilkyWay-2 supercomputer. This study will provide insights into the construction of bioinformatic analysis platform for other subjects. PMID- 26351171 TI - [Genome-wide identification and analyses of 4CL gene families in Pyrus bretschneideri Rehd]. AB - 4-coumaric acid: coenzyme A ligase (4CL) gene is one of the key genes involved in the regulation of lignin metabolism and the synthesis of flavonoid and other secondary metabolites in plant, while the synthesized and polymerized lignin is deposited in cell walls and leads to thickening of secondary walls in some parenchyma cells and formation of stone cells. To better understand the variety and quantity of 4CL genes in Pyrus bretschneideri Rehd., we used the amino acid and cDNA databases of Pyrus bretschneideri Rehd. genome to screen 4CL gene family, and analyzed their classification, evolutionary relationships, physical location, gene structure and conserved motif. Our results showed that 29 4CL genes were identified and preliminarily characterized, and these 4CL genes were distributed in all chromosomes except chromosomes 4, 8, 11, 12 and clustered on chromosomes 9 and 17 through gene location analysis. The relationship between 4CL gene structure and evolution was further determined by comparing gene structure and phylogenetic tree. These findings provide a basis for further analysis of 4CL gene function in Pyrus bretschneideri Rehd. PMID- 26351172 TI - [Genome-wide identification and expression analysis of auxin-related gene families in grape]. AB - The auxin response gene family adjusts the auxin balance and the growth hormone signaling pathways in plants. Using bioinformatics methods, the auxin-response genes from the grape genome database are identified and their chromosomal location, gene collinearity and phylogenetic analysis are performed. Probable genes include 25 AUX_IAA, 19 ARF, 9 GH3 and 42 LBD genes, which are unevenly distributed on all 19 chromosomes and some of them formed distinct tandem duplicate gene clusters. The available grape microarray databases show that all of the auxin-response genes are expressed in fruit and leaf buds, and significant overexpressed during fruit color-changing, bud break and bud dormancy periods. This paper provides a resource for functional studies of auxin-response genes in grape leaf and fruit development. PMID- 26351173 TI - Differentially expressed urinary biomarkers in children with idiopathic nephrotic syndrome. AB - BACKGROUND: We performed a discovery phase of urinary proteomic profile in children with idiopathic nephrotic syndrome and validated selected biomarkers. METHODS: Urinary proteomic profile was performed using isobaric tags for relative and absolute quantitation labeling, coupled with liquid chromatography-matrix assisted laser desorption and ionization analysis. Validation of biomarkers apolipoprotein A1, alpha 2 macroglobulin, orosomucoid 2, retinol binding protein 4 and leucine-rich alpha 2-glycoprotein 1 was done by enzyme-linked immunosorbent assay. RESULTS: Apolipoprotein A1 levels of <0.48 ug/mg of creatinine differentiated steroid-resistant nephrotic syndrome (SRNS) from first episode nephrotic syndrome, area under curve (AUC) [0.99 (CI 0.9-1.0), 100 % sensitivity and 100 % specificity] and a value of <0.24 ug/mg of creatinine could differentiate SRNS from frequently relapsing nephrotic syndrome/steroid dependent nephrotic syndrome [AUC 0.99 (CI 0.9-1.0), 100 % sensitivity and 100 % specificity]. Alpha 2 macroglobulin could differentiate children with SRNS-focal segmental glomerulosclerosis (FSGS) from SRNS-minimal change disease (MCD) at values >3.3 ug/mg of creatinine [AUC 0.84 (CI 0.62-1.0), 90 % sensitivity and 85 % specificity]. Orosomucoid 2 >1.81 ug/mg of creatinine could distinguish SRNS FSGS from SRNS-MCD [AUC 0.84 (CI 0.62-1.0), sensitivity 90 % and specificity 85.5 %]. RBP 4 value of >1.54 ug/mg of creatinine differentiated SRNS-FSGS from SRNS MCD [AUC 0.87 (CI 0.68-1.0), sensitivity 90 % and specificity 85.7 %]. CONCLUSIONS: Lower level of apolipoprotein A1 in urine is suggestive of SRNS. Alpha 2 macroglobulin, retinol binding protein 4 and orosomucoid 2 are markers associated with FSGS, with alpha 2 macroglobulin being most predictive. PMID- 26351174 TI - Role of Autophagy in Capsaicin-Induced Apoptosis in U251 Glioma Cells. AB - In recent years, the role of capsaicin in cancer prevention and treatment has gained people's attention. However, the mechanism of anti-glioma cells by capsaicin has not been elucidated. Here, we discuss the mechanism of capsaicin in U251 cells. Cell viability was detected by MTT and extracellular LDH measurements, while immunofluorescence was performed to measure changes of LC3 in U251 cells. The expressions of LC3II, Puma-alpha, Beclin1, P62, Procaspase-3, and P53 were observed by immunoblotting. The cell viability decreased and the punctate patterns of LC3 in U251 cells were observed after Capsaicin treatment. Meanwhile, the expressions of Beclin1, P62, and Puma-alpha increased. After using 3-MA, the expressions of Beclin1 and Procaspase-3 were reduced while those of P53 and Puma-alpha increased. The expression of LC3II was increased after Pifithrin alpha treatment. Therefore, we believed that capsaicin could induce apoptosis in U251 cells, and the inhibition of autophagy could contribute to apoptosis. PMID- 26351175 TI - Transition Metal Oxides for the Oxygen Reduction Reaction: Influence of the Oxidation States of the Metal and its Position on the Periodic Table. AB - Electrocatalysts have been developed to meet the needs and requirements of renewable energy applications. Metal oxides have been well explored and are promising for this purpose, however, many reports focus on only one or a few metal oxides at once. Herein, thirty metal oxides, which were either commercially available or synthesized by a simple and scalable method, were screened for comparison with regards to their electrocatalytic activity towards the oxygen reduction reaction (ORR). We show that although manganese, iron, cobalt, and nickel oxides generally displayed the ability to enhance the kinetics of oxygen reduction under alkaline conditions compared with bare glassy carbon, there is no significant correlation between the position of a metal on the periodic table and the electrocatalytic performance of its respective metal oxides. Moreover, it was also observed that mixed valent (+2, +3) oxides performed the poorest, compared with their respective pure metal oxides. These findings may be of paramount importance in the field of renewable energy. PMID- 26351176 TI - Stage 2 hypertension: predictors of failure to achieve blood pressure control and the impact of adding one additional antihypertensive class. AB - BACKGROUND AND OBJECTIVE: Controlling blood pressure (BP) for patients with stage 2 hypertension remains challenging. This research aimed to: (i) identify predictors of failure to achieve BP control, (ii) determine the association of adding one additional antihypertensive class with achieving BP control, and (iii) describe the prescribed antihypertensive regimens. METHODS: Electronic medical record data from 25 multi-specialty medical groups in the USA were used. The study cohort included patients with stage 2 hypertension in 2012. BP control rates were determined at 6 months from the date of the stage 2 BP. Using multivariable logistic regression and validation by Monte Carlo simulation, we determined independent baseline predictors of not achieving BP control (<140/90). RESULTS: Included were 107 903 patients. Baseline predictors of failure to achieve BP control included the following: a prior stage 2 BP, systolic BP >= 165, Black race, male sex, income <= $35 000, body mass index >= 30, age >= 65 years, and no office visits. Increasing from single-class to dual-class antihypertensive therapy was associated with a 42% increased odds of achieving BP control (odds ratio 1.42; 95% CI 1.22, 1.64); however, this effect was attenuated as the number of baseline antihypertensive classes increased. The 10 most frequently prescribed regimens accounted for only 40% of all antihypertensive regimens. CONCLUSIONS: Among patients with stage 2 hypertension, a prior stage 2 BP, a systolic BP >= 165, and fewer office visits were strong predictors of failure to achieve BP control. Increasing to dual-class antihypertensive therapy was significantly associated with achieving BP control. There is broad heterogeneity in the antihypertensive regimens prescribed. PMID- 26351177 TI - Identification of a Novel Mutation in the SLC39A4 Gene in a Case of Acrodermatitis Enteropathica. PMID- 26351178 TI - A novel four- and pseudo-five-component reaction: unexpected efficient one-pot synthesis of 4H-thiopyran derivatives. AB - A facile and convenient novel method is reported for the synthesis of substituted 4H-thiopyrans by reacting aldehydes, malononitrile, carbon disulfide, and primary amines at room temperature in the presence of triethylamine as a catalyst. This reaction affords the desired products in high purity and has advantages of excellent yields, simple work-up procedure, and short reaction time. PMID- 26351179 TI - Experiences with, perceptions of and attitudes towards traditional Korean medicine (TKM) in patients with chronic fatigue: a qualitative, one-on-one, in depth interview study. AB - OBJECTIVES: To explore perceptions and experiences of patients with chronic fatigue with traditional Korean medicine (TKM) and their motivation for choosing TKM. DESIGN: Qualitative, one-on-one, in-depth interview study. SETTING: Primary TKM hospitals in Seoul, Incheon and Daejeon, South Korea. RESULTS: 15 patients with chronic fatigue were interviewed in this study. Patients with chronic fatigue experienced physical and psychological symptoms that resulted in severe difficulties associated with routine daily activities. The motivations for choosing TKM were primarily dissatisfaction with conventional medicine and previous positive experiences with TKM. While undergoing TKM treatment, patients found that TKM practitioners considered fatigue to be a treatable illness; also, patients felt comfortable with the doctor-patient relationship in TKM. CONCLUSIONS: Healthcare providers need to be concerned about the symptoms of chronic fatigue to a degree that is in line with the patient's own perceptions. Korean patients with chronic fatigue choose TKM as an alternative to fulfil their long-term needs that were unmet by conventional medicine, and they are greatly positively influenced by TKM. TKM may present a possible therapy to alleviate symptoms of diseases that conventional medicine does not address and is an approach that has a considerable effect on Korean patients. PMID- 26351180 TI - Fertility outcome analysis after surgical management of tubal ectopic pregnancy: a retrospective cohort study. AB - OBJECTIVES: To compare the subsequent fertility and risk of recurrence of an ectopic pregnancy (EP) in women who had had an EP, according to the type of surgical treatment they received--that is, salpingectomy, salpingostomy or tubal anastomosis. METHODS: A retrospective cohort study was carried out between January 2003 and September 2011 of 618 patients admitted to hospital with tubal EP and who had received surgical treatment (salpingectomy, n=434; salpingostomy, n=112; and tube anastomosis, n=72). Main outcomes included the first intrauterine pregnancy (IUP) and recurrent EP. RESULTS: The crude IUP rates up to 24 months after surgery were 55.5% for salpingectomy, 50.9% for salpingostomy and 40.3% for tubal anastomosis treatments. In the multivariate-adjusted model, with the patients receiving salpingectomy as the reference group, HR for patients after salpingostomy and tubal anastomosis treatments for IUP were 0.912 (95% CI 0.762 to 2.017) and 0.619 (95% CI 0.328 to 0.927), respectively. The 2-year cumulative recurrent EP rates were found to be 8.1% for salpingectomy, 6.3% for salpingostomy and 16.7% for tubal anastomosis treatments. Taking the patients receiving salpingectomy as the reference group, the patients who received tubal anastomosis had a positively higher risk of recurrent EP (HR=2.280; 95% CI 1.121 to 4.636) in univariate analysis. Adjustment for other potential confounders only slightly attenuated the HR. CONCLUSIONS: The patients with an EP receiving tubal anastomosis treatments appeared to have a lower 2-year rate of IUP and a higher risk of recurrent EP after adjustment for other potential risk factors. PMID- 26351181 TI - Lung protective ventilation in patients undergoing major surgery: a systematic review incorporating a Bayesian approach. AB - OBJECTIVE: Protective ventilation (PV) has been validated in patients with acute respiratory distress syndrome. However, the effect of PV in patients undergoing major surgery is controversial. The study aimed to explore the beneficial effect of PV on patients undergoing a major operation by systematic review and meta analysis. SETTING: Various levels of medical centres. PARTICIPANTS: Patients undergoing general anaesthesia. INTERVENTIONS: PV with low tidal volume. PRIMARY AND SECONDARY OUTCOME MEASURES: Study end points included acute lung injury (ALI), pneumonia, atelectasis, mortality, length of stay (LOS) in intensive care unit (ICU) and hospital. METHODS: Databases including PubMed, Scopus, EBSCO and EMBASE were searched from inception to May 2015. Search strategies consisted of terms related to PV and anaesthesia. We reported OR for binary outcomes including ALI, mortality, pneumonia, atelectasis and other adverse outcomes. Weighted mean difference was reported for continuous outcomes such as LOS in the ICU and hospital, pH value, partial pressure of carbon dioxide, oxygenation and duration of mechanical ventilation (MV). MAIN RESULTS: A total of 22 citations were included in the systematic review and meta-analysis. PV had protective effect against the development of ALI as compared with the control group, with an OR of 0.41 (95% CI 0.19 to 0.87). PV tended to be beneficial with regard to the development of pneumonia (OR 0.46, 95% CI 0.16 to 1.28) and atelectasis (OR 0.68, 95% CI 0.46 to 1.01), but statistical significance was not reached. Other adverse outcomes such as new onset arrhythmia were significantly reduced with the use of PV (OR 0.47, 95% CI 0.48 to 0.93). CONCLUSIONS: The study demonstrates that PV can reduce the risk of ALI in patients undergoing major surgery. However, there is insufficient evidence that such a beneficial effect can be translated to more clinically relevant outcomes such as mortality or duration of MV. TRIAL REGISTRATION NUMBER: The study was registered in PROSPERO (http://www.crd.york.ac.uk/PROSPERO/) under registration number CRD42013006416. PMID- 26351182 TI - Capturing the experiences of patients across multiple complex interventions: a meta-qualitative approach. AB - OBJECTIVES: The perspectives, needs and preferences of individuals with complex health and social needs can be overlooked in the design of healthcare interventions. This study was designed to provide new insights on patient perspectives drawing from the qualitative evaluation of 5 complex healthcare interventions. SETTING: Patients and their caregivers were recruited from 5 interventions based in primary, hospital and community care in Ontario, Canada. PARTICIPANTS: We included 62 interviews from 44 patients and 18 non-clinical caregivers. INTERVENTION: Our team analysed the transcripts from 5 distinct projects. This approach to qualitative meta-evaluation identifies common issues described by a diverse group of patients, therefore providing potential insights into systems issues. OUTCOME MEASURES: This study is a secondary analysis of qualitative data; therefore, no outcome measures were identified. RESULTS: We identified 5 broad themes that capture the patients' experience and highlight issues that might not be adequately addressed in complex interventions. In our study, we found that: (1) the emergency department is the unavoidable point of care; (2) patients and caregivers are part of complex and variable family systems; (3) non-medical issues mediate patients' experiences of health and healthcare delivery; (4) the unanticipated consequences of complex healthcare interventions are often the most valuable; and (5) patient experiences are shaped by the healthcare discourses on medically complex patients. CONCLUSIONS: Our findings suggest that key assumptions about patients that inform intervention design need to be made explicit in order to build capacity to better understand and support patients with multiple chronic diseases. Across many health systems internationally, multiple models are being implemented simultaneously that may have shared features and target similar patients, and a qualitative meta evaluation approach, thus offers an opportunity for cumulative learning at a system level in addition to informing intervention design and modification. PMID- 26351183 TI - Diet and physical activity for children's health: a qualitative study of Nepalese mothers' perceptions. AB - OBJECTIVES: Non-communicable diseases account for 50% of all deaths in Nepal and 25% result from cardiovascular diseases. Previous studies in Nepal indicate a high burden of behavioural cardiovascular risk factors, suggesting a low level of knowledge, attitude and practice/behaviour regarding cardiovascular health. The behavioural foundation for a healthy lifestyle begins in early childhood, when mothers play a key role in their children's lives. This qualitative study, conducted in a Nepalese peri-urban community, aimed to explore mothers' perception of their children's diet and physical activity. DESIGN: We notated, tape-recorded and transcribed all data collected from six focus group discussions, and used qualitative content analysis for evaluation and interpretation. SETTING: The study was conducted in the Jhaukhel-Duwakot Health Demographic Surveillance Site in the Bhaktapur district of Nepal. PARTICIPANTS: Local health workers helped recruit 61 women with children aged 5-10 years. We distributed participants among six different groups according to educational status. RESULTS: Although participants understood the importance of healthy food, they misunderstood its composition, perceiving it as unappetising and appropriate only for sick people. Furthermore, participants did not prioritise their children's physical activities. Moreover, mothers believed they had limited control over their children's dietary habits and physical activity. Finally, they opined that health educational programmes would help mothers and recommended various intervention strategies to increase knowledge regarding a healthy lifestyle. CONCLUSIONS: Our data reveal that mothers of young children in a peri urban community of Nepal lack adequate and accurate understanding about the impact of a healthy diet and physical activity. Therefore, to prevent future cardiovascular disease and other non-communicable diseases among children, Nepal needs health education programmes to improve mothers' cardiovascular health knowledge, attitude and behaviour. PMID- 26351184 TI - Comparison of the university hospital and county hospitals in western Sweden to identify potential weak links in the early chain of care for acute stroke: results of an observational study. AB - OBJECTIVE: To identify weak links in the early chain of care for acute stroke. SETTING: 9 emergency hospitals in western Sweden, each with a stroke unit, and the emergency medical services (EMS). PARTICIPANTS: All patients hospitalised with a first and a final diagnosis of stroke-between 15 December 2010 and 15 April 2011. The university hospital in the city of Gothenburg was compared with 6 county hospitals. PRIMARY AND SECONDARY MEASURES: (1) The system delay, that is, median delay time from call to the EMS until diagnosis was designated as the primary end point. Secondary end points were: (2) the system delay time from call to the EMS until arrival in a hospital ward, (3) the use of the EMS, (4) priority at the dispatch centre and (5) suspicion of stroke by the EMS nurse. RESULTS: In all, 1376 acute patients with stroke (median age 79 years; 49% women) were included. The median system delay from call to the EMS until (1) diagnosis (CT scan) and (2) arrival in a hospital ward was 3 h and 52 min and 4 h and 22 min, respectively. The system delay (1) was significantly shorter in county hospitals. (3) The study showed that 76% used the EMS (Gothenburg 71%; the county 79%; p<0.0001). (4) Priority 1 was given at the dispatch centre in 54% of cases. (5) Stroke was suspected in 65% of cases. A prenotification was sent in 32% (Gothenburg 52%; the county 20%; p<0.0001). CONCLUSIONS: System delay is still long and only a small fraction of patients received thrombolysis. Three of four used the EMS (more frequent in the county). They were given the highest priority at the dispatch centre in half of the cases. Stroke was suspected in two-thirds of the cases, but a prenotification was seldom sent to the hospital. PMID- 26351185 TI - Factors related to previous tuberculosis treatment of patients with multidrug resistant tuberculosis in Bangladesh. AB - OBJECTIVE: Previous tuberculosis (TB) treatment status is an established risk factor for multidrug-resistant TB (MDR-TB). This study explores which factors related to previous TB treatment may lead to the development of multidrug resistant in Bangladesh. DESIGN: We previously conducted a large case-control study to identify risk factors for developing MDR-TB in Bangladesh. Patients who had a history of previous TB treatment, either MDR-TB or non-MDR-TB, were interviewed about their previous treatment episode. This study restricts analysis to the strata of patients who have been previously treated for TB. Information was collected through face-to-face interviews and record reviews. Unadjusted and multivariable logistic regression was used for data analysis. SETTING: Central level, district-level and subdistrict-level hospitals in rural and urban Bangladesh. RESULTS: The strata of previously treated patients include a total of 293 patients (245 current MDR-TB; 48 non-MDR-TB). Overall, 54% of patients received previous TB treatment more than once, and all of these patients were multidrug resistant. Patients with MDR-TB were more likely to have experienced the following factors: incomplete treatment (OR 4.3; 95% CI 1.7 to 10.6), adverse reactions due to TB treatment (OR 8.2; 95% CI 3.2 to 20.7), hospitalisation for symptoms associated with TB (OR 16.9; CI 1.8 to 156.2), DOTS (directly observed treatment, short-course) centre as treatment unit (OR 6.4; CI 1.8 to 22.8), supervised treatment (OR 3.8; CI 1.6 to 9.5); time-to-treatment centre (OR 0.984; CI 0.974 to 0.993). CONCLUSIONS: Incomplete treatment, hospitalisation for TB treatment and adverse reaction are the factors related to previous TB treatment of patients with MDR-TB. Although the presence of supervised treatment (DOT), less time-to-treatment centres and being treated in DOTS centres were relatively higher among the patients with MDR-TB compared with patients without MDR-TB, these findings include information of their most recent TB treatment episode only. Most (64.5%) of the patients with MDR-TB had received TB treatment more than once. PMID- 26351186 TI - Mothers' perceptions of the UK physical activity and sedentary behaviour guidelines for the early years (Start Active, Stay Active): a qualitative study. AB - OBJECTIVES: Higher levels of physical activity (PA) during early childhood have been associated with improved health outcomes, whereas sedentary behaviour (SB) has been associated with poorer health outcomes in children. In 2011, the UK produced guidelines for PA and SB in children under 5 years. Mothers have been identified as key influences in young children's PA and SB. The aim of this study was to use in-depth interviews with mothers of preschool children to examine attitudes to the guidance. DESIGN: Qualitative study using one-to-one, semistructured interviews; Data were analysed thematically using a framework approach. SETTING: Mothers were recruited from preschools, nurseries, and mother and toddler groups located in four areas of varying socioeconomic status within Bristol, UK. PARTICIPANTS: 24 mothers who were considered the main or joint carer for a preschool child who was at least 2 years of age but had not yet started formal schooling. RESULTS: Mothers are not aware of the UK PA and SB guidelines for the early years. They believe that their child achieves the guideline targets for PA and SB and therefore, they do not believe these quidelines are relevant to them. Mothers feel that an increase in PA and reduction in SB (especially screen viewing) would cause stress for mothers. Mothers found defining and quantifying PA and SB in their preschool child problematic. CONCLUSIONS: As mothers do not identify with the need to increase PA or reduce SB in their child, awareness of the guidelines alone is unlikely to initiate behaviour change. Information on how mothers can make a more accurate assessment of their preschool child's PA and SB levels, and information about the benefits of increased PA and reduced SB should be provided alongside the guideline targets. Clear messages need to be developed that reframe the guidelines into pragmatic and usable targets. PMID- 26351187 TI - Disparities in the completion of steps to kidney transplantation: protocol for a systematic review. AB - INTRODUCTION: Disparities in access to transplantation have been well documented. The extant literature, however, focuses largely on disparities and related barriers for African-American patients and none has used the steps to transplantation as a guiding framework. This review will catalogue disparities in the steps to transplantation as well as the barriers and facilitators to completion of each step identified in the extant literature. The results of the review will be used to generate recommendations for future research to improve equity in access to kidney transplantation. METHODS AND ANALYSIS: Standard procedures will be used in the conduct of the review. Searches will be performed using the following electronic databases: PubMed/Medline, PsycINFO, CINHAL, EMBASE, Cochrane library and Web of Science. Reports of original research will be eligible for inclusion if they are published from 2005 to present, written or available in English language, performed in the USA, enrol adult participants (18 years of age or more), and employ descriptive or observational designs. Two authors will independently screen retrieved articles for inclusion. MaxQDA will be used for data analysis and management. All included reports will be coded for article characteristics; disparities identified; barriers and motivators of completion of steps to transplantation; and proposed solutions to disparities and barriers. Each report will be coded independently by two authors and discrepancies resolved by discussion among the full team. A qualitative approach to data analysis is planned. Risk of bias will be assessed using standard procedures. ETHICS AND DISSEMINATION: The findings will provide crucial information on the current status of disparities in access to transplantation. PRISMA guidelines will be followed in reporting the results of the review. It is anticipated that these results will inform research which seeks to increase parity in access to transplantation. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42014015027. PMID- 26351188 TI - Service availability and association between Mutuelles and medical care usage for under-five children in rural Rwanda: a statistical analysis with repeated cross sectional data. AB - OBJECTIVE: To compare the association between Mutuelles enrolment and medical care utilisation among under-five rural children between 2005 and 2010; that is, before and after substantial improvements in service availability took place in rural areas. METHODS: We tracked the change in service availability between 2005 and 2010. Using the nationally representative population-based Rwanda Demographic and Health Surveys 2005 and 2010, we conducted a statistical analysis using multilevel logistic random-effects models. We included Mutuelles enrollees and uninsured children who had diarrhoea, cough or fever in the previous 2 weeks of the surveys. The final sample size was 4071 children. RESULTS: We observed a substantial increase in the availability of health facilities, medical staff and child health services from 2005 to 2010. In both years, under-five children with Mutuelles were more likely to use medical care than uninsured children. Children in 2010 had a higher probability of using medical care than their counterparts in 2005, regardless of the children's poverty or Mutuelles status. Mutuelles enrollees in 2010 had the highest probability of using care among children in both years. The findings were robust to model specifications and estimation methods. CONCLUSIONS: This study suggests the importance of strengthening service provision at the supply side in promoting equitable utilisation of childcare with prepayment schemes. PMID- 26351189 TI - Comparing clinical quality indicators for asthma management in children with outcome measures used in randomised controlled trials: a protocol. AB - INTRODUCTION: Clinical quality indicators are necessary to monitor the performance of healthcare services. The development of indicators should, wherever possible, be based on research evidence to minimise the risk of bias which may be introduced during their development, because of logistic, ethical or financial constraints alone. The development of automated methods to identify the evidence base for candidate indicators should improve the process of indicator development. The objective of this study is to explore the relationship between clinical quality indicators for asthma management in children with outcome and process measurements extracted from randomised controlled clinical trial reports. METHODS AND ANALYSIS: National-level indicators for asthma management in children will be extracted from the National Quality Measures Clearinghouse (NQMC) database and the National Institute for Health and Care Excellence (NICE) quality standards. Outcome measures will be extracted from published English language randomised controlled trial (RCT) reports for asthma management in children aged below 12 years. The two sets of measures will be compared to assess any overlap. The study will provide insights into the relationship between clinical quality indicators and measurements in RCTs. This study will also yield a list of measurements used in RCTs for asthma management in children, and will find RCT evidence for indicators used in practice. ETHICS AND DISSEMINATION: Ethical approval is not necessary because this study will not include patient data. Findings will be disseminated through peer-reviewed publications. PMID- 26351190 TI - Counting the costs of accreditation in acute care: an activity-based costing approach. AB - OBJECTIVES: To assess the costs of hospital accreditation in Australia. DESIGN: Mixed methods design incorporating: stakeholder analysis; survey design and implementation; activity-based costs analysis; and expert panel review. SETTING: Acute care hospitals accredited by the Australian Council for Health Care Standards. PARTICIPANTS: Six acute public hospitals across four States. RESULTS: Accreditation costs varied from 0.03% to 0.60% of total hospital operating costs per year, averaged across the 4-year accreditation cycle. Relatively higher costs were associated with the surveys years and with smaller facilities. At a national level these costs translate to $A36.83 million, equivalent to 0.1% of acute public hospital recurrent expenditure in the 2012 fiscal year. CONCLUSIONS: This is the first time accreditation costs have been independently evaluated across a wide range of hospitals and highlights the additional cost burden for smaller facilities. A better understanding of the costs allows policymakers to assess alternative accreditation and other quality improvement strategies, and understand their impact across a range of facilities. This methodology can be adapted to assess international accreditation programmes. PMID- 26351191 TI - Smoking in the home after childbirth: prevalence and determinants in an English cohort. AB - OBJECTIVES: Children's exposure to secondhand smoke (SHS) is causally linked to childhood morbidity and mortality. Over 38% of English children (aged 4-15) whose parents are smokers are exposed to SHS in the home. Little is known about the prevalence of SHS exposure in the homes of young infants (<=3 months). This study aimed to estimate maternal self-reported prevalence of SHS exposure among infants of women who smoked just before or during pregnancy, and identify factors associated with exposure. SETTING: Primary Care, Nottingham, England. PARTICIPANTS: Current and recent ex-smoking pregnant women (n=850) were recruited in Nottingham, England. Women completed questionnaires at 8-26 weeks gestation and 3 months after childbirth. Data on smoking in the home 3 months after childbirth was available for 471 households. PRIMARY AND SECONDARY OUTCOME MEASURES: Maternal-reported smoking in the home 3 months after childbirth. RESULTS: The prevalence of smoking in the home 3 months after childbirth was 16.3% (95% CI 13.2% to 19.8%) and after multiple imputation controlling for non response 18.2% (95% CI 14.0% to 22.5%). 59% of mothers were current smokers; of these, 24% reported that smoking occurred in their home compared to 4.7% of non smokers. In multivariable logistic regression, mothers smoking >=11 cigarettes per day were 8.2 times (95% CI 3.4 to 19.6) more likely to report smoking in the home. Younger age, being of non-white ethnicity, increased deprivation and less negative attitudes towards SHS were also associated with smoking in the home. CONCLUSIONS: This survey of smoking in the home 3 months after childbirth found a lower prevalence than has been reported in older children. Interventions to support smoking mothers to quit, or to help them restrict smoking in the home, should target attitudinal change and address inequality relating to social disadvantage, younger age and non-white ethnic groups. PMID- 26351192 TI - The Deyo-Charlson and Elixhauser-van Walraven Comorbidity Indices as predictors of mortality in critically ill patients. AB - OBJECTIVES: Our primary objective was to compare the utility of the Deyo-Charlson Comorbidity Index (DCCI) and Elixhauser-van Walraven Comorbidity Index (EVCI) to predict mortality in intensive care unit (ICU) patients. SETTING: Observational study of 2 tertiary academic centres located in Boston, Massachusetts. PARTICIPANTS: The study cohort consisted of 59,816 patients from admitted to 12 ICUs between January 2007 and December 2012. PRIMARY AND SECONDARY OUTCOME: For the primary analysis, receiver operator characteristic curves were constructed for mortality at 30, 90, 180, and 365 days using the DCCI as well as EVCI, and the areas under the curve (AUCs) were compared. Subgroup analyses were performed within different types of ICUs. Logistic regression was used to add age, race and sex into the model to determine if there was any improvement in discrimination. RESULTS: At 30 days, the AUC for DCCI versus EVCI was 0.65 (95% CI 0.65 to 0.67) vs 0.66 (95% CI 0.65 to 0.66), p=0.02. Discrimination improved at 365 days for both indices (AUC for DCCI 0.72 (95% CI 0.71 to 0.72) vs AUC for EVCI 0.72 (95% CI 0.72 to 0.72), p=0.46). The DCCI and EVCI performed similarly across ICUs at all time points, with the exception of the neurosciences ICU, where the DCCI was superior to EVCI at all time points (1-year mortality: AUC 0.73 (95% CI 0.72 to 0.74) vs 0.68 (95% CI 0.67 to 0.70), p=0.005). The addition of basic demographic information did not change the results at any of the assessed time points. CONCLUSIONS: The DCCI and EVCI were comparable at predicting mortality in critically ill patients. The predictive ability of both indices increased when assessing long-term outcomes. Addition of demographic data to both indices did not affect the predictive utility of these indices. Further studies are needed to validate our findings and to determine the utility of these indices in clinical practice. PMID- 26351193 TI - The influence of snoring, mouth breathing and apnoea on facial morphology in late childhood: a three-dimensional study. AB - OBJECTIVE: To explore the relationship between the prevalence of sleep disordered breathing (SDB) and face shape morphology in a large cohort of 15-year-old children. DESIGN: Observational longitudinal cohort study SETTING: Avon Longitudinal Study of Parents and Children (ALSPAC), South West of England. PARTICIPANTS: Three-dimensional surface laser scans were taken for 4784 white British children from the ALSPAC during a follow-up clinic. A total of 1724 children with sleep disordered breathing (SDB) and 1862 healthy children were identified via parents' report of sleep disordered symptoms for their children. We excluded from the original cohort all children identified as having congenital abnormalities, diagnoses associated with poor growth and children with adenoidectomy and/or tonsillectomy. MAIN OUTCOME MEASURES: Parents in the ALSPAC reported sleep disordered symptoms (snoring, mouth breathing and apnoea) for their children at 6, 18, 30, 42, 57, 69 and 81 months. Average facial shells were created for children with and without SDB in order to explore surface differences. RESULTS: Differences in facial measurements were found between the children with and without SDB throughout early childhood. The mean differences included an increase in face height in SDB children of 0.3 mm (95% CI -0.52 to 0.05); a decrease in mandibular prominence of 0.9 degrees (95% CI -1.30 to 0.42) in SDB children; and a decrease in nose prominence and width of 0.12 mm (95% CI 0.00 to 0.24) and 0.72 mm (95% CI -0.10 to -0.25), respectively, in SDB children. The odds of children exhibiting symptoms of SDB increased significantly with respect to increased face height and mandible angle, but reduced with increased nose width and prominence. CONCLUSIONS: The combination of a long face, reduced nose prominence and width, and a retrognathic mandible may be diagnostic facial features of SBD that may warrant a referral to specialists for the evaluation of other clinical symptoms of SDB. PMID- 26351194 TI - A retrospective analysis of the effect of discussion in teleconference and face to-face scientific peer-review panels. AB - OBJECTIVE: With the use of teleconferencing for grant peer-review panels increasing, further studies are necessary to determine the efficacy of the teleconference setting compared to the traditional onsite/face-to-face setting. The objective of this analysis was to examine the effects of discussion, namely changes in application scoring premeeting and postdiscussion, in these settings. We also investigated other parameters, including the magnitude of score shifts and application discussion time in face-to-face and teleconference review settings. DESIGN: The investigation involved a retrospective, quantitative analysis of premeeting and postdiscussion scores and discussion times for teleconference and face-to-face review panels. The analysis included 260 and 212 application score data points and 212 and 171 discussion time data points for the face-to-face and teleconference settings, respectively. RESULTS: The effect of discussion was found to be small, on average, in both settings. However, discussion was found to be important for at least 10% of applications, regardless of setting, with these applications moving over a potential funding line in either direction (fundable to unfundable or vice versa). Small differences were uncovered relating to the effect of discussion between settings, including a decrease in the magnitude of the effect in the teleconference panels as compared to face-to-face. Discussion time (despite teleconferences having shorter discussions) was observed to have little influence on the magnitude of the effect of discussion. Additionally, panel discussion was found to often result in a poorer score (as opposed to an improvement) when compared to reviewer premeeting scores. This was true regardless of setting or assigned reviewer type (primary or secondary reviewer). CONCLUSIONS: Subtle differences were observed between settings, potentially due to reduced engagement in teleconferences. Overall, further research is required on the psychology of decision-making, team performance and persuasion to better elucidate the group dynamics of telephonic and virtual ad-hoc peer-review panels. PMID- 26351195 TI - A retrospective pilot study of correlation of cerebral augmentation effects of external counterpulsation with functional outcome after acute ischaemic stroke. AB - OBJECTIVE: External counterpulsation (ECP) is a non-invasive method used to augment cerebral blood flow of patients with ischaemic stroke via induced hypertension. We aimed to explore the correlation between the cerebral blood flow augmentation effects induced by ECP and clinical outcome after acute ischaemic stroke. METHODS: We retrospectively analysed our ECP registry of patients with ischaemic stroke who were enrolled within 7 days after stroke onset. Bilateral middle cerebral arteries of patients were monitored using transcranial Doppler (TCD). Flow velocity changes before, during and after ECP were, respectively, recorded for 3 min. The cerebral augmentation index (CAI) was the increase in percentage of the middle cerebral artery mean flow velocity during ECP compared with baseline. TCD data were analysed based on the side ipsilateral or contralateral to the infarct. The modified Rankin Scale (mRS) (good outcome: mRS 0~2; poor outcome: mRS 3~6) was evaluated 6 months after the index stroke. RESULTS: 72 patients were included (mean age, 63.8+/-10.7 years; 87.5% males). At month 6 after stroke onset, univariate analysis showed that the National Institutes of Health Stroke Scale at recruitment was significantly higher and ECP therapy duration was longer in the poor outcome group, while the ipsilateral CAI was significantly lower in the good outcome group than that in the poor outcome group (3.71+/-4.94 vs 7.73+/-7.66, p=0.044). Multivariate logistic regression showed that ipsilateral CAI was independently correlated with an unfavourable functional outcome after adjusting for confounding factors. CONCLUSIONS: The higher degree of cerebral blood flow velocity augmentation on the side ipsilateral to the infarct induced by ECP is independently correlated with an unfavourable functional outcome after acute ischaemic stroke. PMID- 26351196 TI - Reduction of selenite to elemental selenium nanoparticles by activated sludge. AB - Total selenium removal by the activated sludge process, where selenite is reduced to colloidal elemental selenium nanoparticles (BioSeNPs) that remain entrapped in the activated sludge flocs, was studied. Total selenium removal efficiencies with glucose as electron donor (2.0 g chemical oxygen demand (COD) L(-1)) at neutral pH and 30 degrees C gave 2.9 and 6.8 times higher removal efficiencies as compared to the electron donors lactate and acetate, respectively. Total selenium removal efficiencies of 79 (+/-3) and 86 (+/-1) % were achieved in shake flasks and fed batch reactors, respectively, at dissolved oxygen (DO) concentrations above 4.0 mg L(-1) and 30 degrees C when fed with 172 mg L(-1) (1 mM) Na2SeO3 and 2.0 g L(-1) COD of glucose. Continuously operated reactors operating at neutral pH, 30 degrees C and a DO >3 mg L(-1) removed 33.98 and 36.65 mg of total selenium per gram of total suspended solids (TSS) at TSS concentrations of 1.3 and 3.0 g L(-1), respectively. However, selenite toxicity to the activated sludge led to failure of a continuously operating activated sludge reactor at the applied loading rates. This suggests that a higher hydraulic retention time (HRT) or different reactor configurations need to be applied for selenium-removing activated sludge processes. Graphical Abstract Scheme representing the possible mechanisms of selenite reduction at high and low DO levels in the activated sludge process. PMID- 26351197 TI - Influence of abatement of lead exposure in Croatia on blood lead and ALAD activity. AB - We evaluated the effect of lead (Pb) abatement measures in Croatia on blood lead (BPb) concentrations, and delta-aminolevulinic acid dehydratase (ALAD) activity in blood, as a sensitive indicator of early Pb effect. Data on BPb and ALAD activity were obtained from 829 Croatian men (19-64 years of age), with no known occupational exposure to metals. Data obtained in 2008-2009, after the ban of leaded gasoline in Croatia in 2006, were compared with similar data collected in 1981 and 1989, when the concentration of Pb in gasoline was 0.6 g/L. Our results showed a highly significant (p < 0.001) decrease in median BPb from 114.5 (range, 46.0-275.0) MUg/L in 1981/1989 to 30.3 (range, 3.2-140.8) MUg/L in 2008-2009 and an increase in median ALAD activity from 49.8 (range, 24.9-79.4) EU in 1981/1989 to 60.9 (range, 35.8-84.0) EU in 2008-2009. Individual factors influencing BPb values were, in the order of decreasing importance, Pb in ambient air (APb), alcohol consumption, age, and smoking. Increased ALAD activity was significantly associated with the decrease of APb, alcohol consumption, and smoking. These results show that lead abatement measures had a positive impact on both BPb concentrations (73.5% decrease) and the activity of ALAD (22.1% increase) in general population. Our results contribute to growing evidence that ALAD activity may be used as one of the earliest and sensitive diagnostic biomarkers of low level Pb exposure. PMID- 26351199 TI - Foliar applied nanoscale and microscale CeO2 and CuO alter cucumber (Cucumis sativus) fruit quality. AB - There is lack of information about the effects of foliar applied nanoparticles on fruit quality. In this study, three week-old soil grown cucumber seedlings were foliar-exposed to nCeO2, nCuO, and corresponding bulk counterparts at 50, 100, and 200mg/L. Respective suspensions/solutions were sprayed to experimental units in a volume of 250ml. Net photosynthesis rate (Pn), stomatal conductance (Gs), and transpiration rate (E) were measured 15days after treatment application and in 74day-old plants. Yield, fruit characteristics (size, weight, and firmness), Ce, Cu, and nutritional elements were also measured. Results showed a nano specific decrement on Pn (22% and 30%) and E (11% and 17%) in seedling leaves exposed to nCeO2 and nCuO at 200mg/L, respectively, compared with control. nCeO2 at 50mg/L, bCeO2 at 200mg/L, and all Cu treatments, except nCuO at 100mg/L, significantly reduced fruit firmness (p<=0.05), compared with control. However, nCuO at 200mg/L and bCuO at 50mg/L significantly increased fruit fresh weight (p<=0.05). At 200mg/L, nCeO2 and bCeO2 reduced fruit Zn by 25%, while nCuO and bCuO reduced fruit Mo by 51% and 44%, respectively, compared with control. This study has shown that when the route of exposure is the foliage, differences in particle size are less significant, compared to root-based exposure. To the authors' knowledge, this is the first report on the effect of foliar application of nCeO2 and nCuO upon yield and nutritional quality of cucumber. PMID- 26351198 TI - Environmental and biological monitoring of occupational formaldehyde exposure resulting from the use of products for hair straightening. AB - The evaluation of formaldehyde (FD) exposure in beauty salons, due to the use of hair straightening products, and its relation with genotoxicity biomarkers was performed in this study. Regardless of official recommendations, the inappropriate use of homemade hair creams has became a popular practice in Brazil, and high formaldehyde content in the "progressive straightening" creams can contain mutagens that could increase the incidence of neoplasia in those people who use them. Damage to DNA was assessed by conducting a micronuclei test (MNT) on buccal cells and the comet assay on heparinized venous blood samples. A total of 50 volunteers were recruited at six different beauty salons (labeled A to F). At two salons that used products that did not contain FD (salons D and E), environmental FD concentrations were 0.04 and 0.02 ppm. In contrast, the products used at salons A, B, C, and F contained 5.7, 2.61, 5.9, and 5.79% of FD, and these salons had environmental FD concentrations of 0.07, 0.14, 0.16, and 0.14 ppm, respectively. Comparison of the beauty salon workers from each of the six beauty salons revealed significant differences in urinary formic acid (FA) concentration before exposure (p = 0.016), urinary FA after exposure (p = 0.004), variation in FA concentration before and after exposure (p = 0.018), environmental FD concentration (p < 0.001), cytogenetic damage detected by the comet assay according to both damage index (p < 0.001) and frequency of damage (p < 0.001), and for karyorrhexis only according to the MNT (p = 0.001). PMID- 26351200 TI - Legacy phosphorus and no tillage agriculture in tropical oxisols of the Brazilian savanna. AB - Crop production in the Brazilian Cerrado is limited by soil phosphorus (P) supply without large inputs of inorganic P fertilizer, which may become more costly and scarce in the future. Reducing dependency on fertilizer P requires a greater understanding of soil P supply in the highly weathered soils in this important agricultural region. We investigated the impact of no tillage (NT) and conventional tillage (CT) agriculture on accumulated (legacy) soil P and P forms in four long-term sites. Compared to the native savanna soils, tilled soils receiving regular annual P fertilizer inputs (30-50 kg P ha(-1)) increased all forms of inorganic and organic P, except highly recalcitrant P associated with the background lithology. However, 70-85% of the net added P was bound in moderately labile and non-labile forms associated with Fe/Al oxyhydroxides rather than in plant available forms. Under NT agriculture, organic P forms and labile and non-labile inorganic P forms were all significantly (P<0.05) increased in the surface soil, except for one site with maize residues where labile inorganic P was increased more under CT agriculture. The contribution of organic P cycling in these tropical soils increased after conversion to agriculture and was proportionally greater under NT. The results highlight the large amounts of unutilized legacy P present in Brazil's Cerrado soils that could be better exploited to reduce dependency on imports of finite phosphate rock. No tillage agriculture confers a positive albeit relatively small benefit for soil P availability and overall soil function. PMID- 26351202 TI - Shotgun analysis of the marine mussel Mytilus edulis hemolymph proteome and mapping the innate immunity elements. AB - The marine mussel innate immunity provides protection to pathogen invasion and inflammation. In this regard, the mussel hemolymph takes a main role in the animal innate response. Despite the importance of this body fluid in determining the physiological condition of the animal, little is known about the molecular mechanisms underlying the cellular and humoral responses. In this work, we have applied a MS (nano-LC-MS/MS) strategy integrating genomic and transcriptomic data with the aim to: (i) identify the main protein functional groups that characterize hemolymph and (ii) to map the elements of innate immunity in the marine mussel Mytilus edulis hemolymph proteome. After sample analysis and first protein identification based on MS/MS data comparison, proteins with unknown functions were annotated with blast using public database (nrNCBI) information. Overall 595 hemolymph proteins were identified with high confidence and annotated. These proteins encompass primary cellular metabolic processes: energy production and metabolism of biomolecules, as well as processes related to oxidative stress defence, xenobiotic detoxification, drug metabolism, and immune response. A group of proteins was identified with putative immune effector, receptor, and signaling functions in M. edulis. Data are available via ProteomeXchange with identifier PXD001951 (http://proteomecentral.proteomexchange.org/dataset/PXD001951). PMID- 26351203 TI - Visualizing double-stranded RNA distribution and dynamics in living cells by dsRNA binding-dependent fluorescence complementation. AB - Double-stranded RNA (dsRNA) is an important type of RNA that plays essential roles in diverse cellular processes in eukaryotic organisms and a hallmark in infections by positive-sense RNA viruses. Currently, no in vivo technology has been developed for visualizing dsRNA in living cells. Here, we report a dsRNA binding-dependent fluorescence complementation (dRBFC) assay that can be used to efficiently monitor dsRNA distribution and dynamics in vivo. The system consists of two dsRNA-binding proteins, which are fused to the N- and C-terminal halves of the yellow fluorescent protein (YFP). Binding of the two fusion proteins to a common dsRNA brings the split YFP halves in close proximity, leading to the reconstitution of the fluorescence-competent structure and restoration of fluorescence. Using this technique, we were able to visualize the distribution and trafficking of the replicative RNA intermediates of positive-sense RNA viruses in living cells. PMID- 26351204 TI - Factor structure and aetiological architecture of the BRIEF: A twin study. AB - Executive function is a broad construct that encompasses various processes involved in goal-directed behaviour in non-routine situations (Banich, 2009). The present study uses a sample of 560 5- to 16-year-old twin pairs (M = 11.14, SD = 2.53): 219 monozygotic twin pairs (114 female; 105 male) and 341 dizygotic twin pairs (136 female, 107 male; 98 opposite sex) to extend prior literature by providing information about the factor structure and the genetic and environmental architecture of the Behavior Rating Inventory of Executive Function (BRIEF; Gioia et al., 2000, Child Neuropsychol., 6, 235; Gioia et al., 2000, Behavior rating inventory of executive function, Lutz, FL: Psychological Assessment Resources), a multifaceted rating scale of everyday executive functions. Phenotypic results revealed a 9-scale, 3-factor model best represents the BRIEF structure within the current sample. Results of the genetically sensitive analyses indicated the presence of rater bias/contrast effects for the Initiate, Working Memory, and Task-Monitor scales. Additive genetic and non shared environmental influences were present for the Initiate, Plan/Organize, Organization of Materials, Shift, and Monitor and Self-Monitor scales. Influences on Emotional Control were solely environmental. Interestingly, the aetiological architecture observed was similar to that of performance-based measures of executive function. This observed similarity provided additional evidence for the usefulness of the BRIEF as a measure of 'everyday' executive function. PMID- 26351205 TI - Methodologies and experimental platforms for generating and analysing microarray and mass spectrometry-based omics data to support P4 medicine. AB - Predictive, preventive, personalized and participatory (P4) medicine is an emerging medical model that is based on the customization of all medical aspects (i.e. practices, drugs, decisions) of the individual patient. P4 medicine presupposes the elucidation of the so-called omic world, under the assumption that this knowledge may explain differences of patients with respect to disease prevention, diagnosis and therapies. Here, we elucidate the role of some selected omics sciences for different aspects of disease management, such as early diagnosis of diseases, prevention of diseases, selection of personalized appropriate and optimal therapies based on molecular profiling of patients. After introducing basic concepts of P4 medicine and omics sciences, we review some computational tools and approaches for analysing selected omics data, with a special focus on microarray and mass spectrometry data, which may be used to support P4 medicine. Some applications of biomarker discovery and pharmacogenomics and some experiences on the study of drug reactions are also described. PMID- 26351201 TI - A neuroradiologist's guide to arterial spin labeling MRI in clinical practice. AB - Arterial spin labeling (ASL) is a non-invasive MRI technique to measure cerebral blood flow (CBF). This review provides a practical guide and overview of the clinical applications of ASL of the brain, as well its potential pitfalls. The technical and physiological background is also addressed. At present, main areas of interest are cerebrovascular disease, dementia and neuro-oncology. In cerebrovascular disease, ASL is of particular interest owing to its quantitative nature and its capability to determine cerebral arterial territories. In acute stroke, the source of the collateral blood supply in the penumbra may be visualised. In chronic cerebrovascular disease, the extent and severity of compromised cerebral perfusion can be visualised, which may be used to guide therapeutic or preventative intervention. ASL has potential for the detection and follow-up of arteriovenous malformations. In the workup of dementia patients, ASL is proposed as a diagnostic alternative to PET. It can easily be added to the routinely performed structural MRI examination. In patients with established Alzheimer's disease and frontotemporal dementia, hypoperfusion patterns are seen that are similar to hypometabolism patterns seen with PET. Studies on ASL in brain tumour imaging indicate a high correlation between areas of increased CBF as measured with ASL and increased cerebral blood volume as measured with dynamic susceptibility contrast-enhanced perfusion imaging. Major advantages of ASL for brain tumour imaging are the fact that CBF measurements are not influenced by breakdown of the blood-brain barrier, as well as its quantitative nature, facilitating multicentre and longitudinal studies. PMID- 26351206 TI - Cholangiocarcinoma: Present Status and Molecular Aspects of Diagnosis. AB - Cholangiocarcinomas are neoplasms that involve the epithelial cells of the bile duct, also known as cholangiocytes. This disease is difficult to diagnose early, as most symptoms present late in the disease. In addition, the specific anatomic position can cause periductal extension and result in a very low radical excision rate and a very poor prognosis. Improved understanding of the features underlying the onset of cholangiocarcinoma and its carcinogenic mechanism may lead to early diagnosis and better prognosis. With the development of molecular biology, much has been learned about oncogenes, tumor-suppressor genes, DNA methylation, microRNAs, and the molecular mechanisms of tumor invasion and metastasis. Based on our research and others, this review article will discuss the current status and prospects of early diagnosis of cholangiocarcinoma. PMID- 26351207 TI - Doxorubicin Inhibits Proliferation of Osteosarcoma Cells Through Upregulation of the Notch Signaling Pathway. AB - Doxorubicin plays a major role in the treatment of osteosarcoma disorders. The Notch signaling pathway exerts various biological functions, including cell proliferation, differentiation, and apoptosis. In the present study, we investigated the effects of different doses of doxorubicin on proliferation and apoptosis of osteosarcoma cells with or without Notch signaling. Results found that cellular viability was downregulated while caspase 3 activity and expression were promoted in osteosarcoma cells following treatment with various doses of doxorubicin for 24, 48, and 72 h, and the effects showed a dose- and time dependent manner. Furthermore, it was found that various doses of doxorubicin activated the Notch signaling pathway, shown by the elevated expression of Notch target genes NOTCH1, HEY1, HES1, AND HES5. It was further proved that, after small interfering RNA (siRNA)-mediated knockdown of Notch, the effects of doxorubicin on the viability and apoptosis of osteosarcoma cells were significantly reduced. It was indicated that doxorubicin treatment reduced the proliferation and promoted the apoptosis of osteosarcoma cells, and this effect was mediated by the Notch signaling pathway. PMID- 26351209 TI - AEG-1 Promotes Metastasis Through Downstream AKR1C2 and NF1 in Liver Cancer. AB - Liver cancer is one of the most lethal cancers, but our knowledge of the molecular mechanism underlying this process remains insufficient. Through deep sequencing and expression regulation analysis in liver cancer cells, we identified two novel factors, AKR1C2 (positive factor) and NF1 (negative factor), as the AEG-1 downstream players in the process of metastasis in liver cancer. They were experimentally validated to have the capacities of regulating cell migration, cell invasion, cell proliferation, and EMT. Further clinic expression and animal model evidence confirmed their functions. Together, our findings provide a new insight into the pharmaceutical and therapeutic use of AEG-1 and downstream AKR1C2 and NF1. PMID- 26351208 TI - Combined Use of Metformin and Everolimus Is Synergistic in the Treatment of Breast Cancer Cells. AB - Everolimus inhibits mammalian target of rapamycin (mTOR) and leads to decreased protein synthesis and decreased cancer cell proliferation in many experimental systems. Adenosine 5'-monophosphate-activated protein kinase (AMPK) activators such as metformin have similar actions in keeping with the TSC2/1 pathway linking activation of AMPK to inhibition of mTOR. Histopathological and biochemical studies of breast cancer show frequent dysregulation of the AMPK and the mTOR pathway. Therefore, we investigated the efficacy of the mTOR inhibitor everolimus and metformin in the treatment of breast cancer cells. This study evaluated the in vitro and in vivo effects of everolimus alone or in combination with metformin on breast cancer cells. MTT assay was used to quantify the inhibitory effect of the drugs on breast cancer cells in vitro. SCID mice injected with HCC1428 cells followed by different treatments were used to assess the in vivo efficacy of different agents. Data showed that the combination of everolimus and metformin exerted synergistic inhibitory effects on the growth of breast cancer cells both in culture and in a mouse xenograft model. Further, this combination abrogated S6 and 4EBP1phosphorylation. Collectively, we suggest that the combination of everolimus and metformin may be an effective regimen for treatment of breast cancer, hence warranting further evaluation of the combination in the clinic. PMID- 26351210 TI - Piceatannol Enhances the Antitumor Efficacy of Gemcitabine in Human A549 Non Small Cell Lung Cancer Cells. AB - To enhance the anticancer efficacy of gemcitabine in the treatment of non-small cell lung cancer (NSCLC), the potential synergistic effect of piceatannol on gemcitabine cytotoxicity was investigated in the human NSCLC A459 cell line. The MTT cell viability assay showed that piceatannol significantly enhanced the cytotoxic effects of gemcitabine by lowering the gemcitabine IC50 value. Flow cytometry analysis revealed that piceatannol exerted its pharmacological effect mainly by increasing the late apoptotic population. Western blot analysis showed that gemcitabine induced the expression of the proapoptotic proteins Bad and Bak, and pretreatment with piceatannol further increased Bak expression, leading to an increased number of cells undergoing late apoptosis. The findings from this study show that piceatannol can enhance the cytotoxic effects of gemcitabine by enhancing expression of the proapoptotic protein Bak, thereby providing the rational basis for a novel combination strategy for the treatment of NSCLC. PMID- 26351211 TI - siRNA Suppression of NEDD9 Inhibits Proliferation and Enhances Apoptosis in Renal Cell Carcinoma. AB - Renal cell carcinoma (RCC) is the most lethal of all genitourinary malignancies. NEDD9/HEF1/Cas-L is a member of the Cas protein family and is known as a biomarker in multiple cancer types. In this study, we demonstrate for the first time that NEDD9 was upregulated in RCC tissue and cell lines. Immunohistochemical analysis and quantitative RT-PCR analysis showed low expression of NEDD9 in normal renal tissues and high expression in RCC tissues. In addition, in vitro experiments show that expression of NEDD9 was upregulated in RCC cell lines. Through MTT assay, we observed that NEDD9 knockdown inhibited cell proliferation. Furthermore, flow cytometry analysis showed that NEDD9 downregulation induced apoptosis. Together, our data suggest that abnormal NEDD9 protein expression may be a marker for RCC, and NEDD9 knockdown suppresses cell growth. PMID- 26351212 TI - Knockdown of Wip1 Enhances Sensitivity to Radiation in HeLa Cells Through Activation of p38 MAPK. AB - The objectives of the study were to investigate the functional role and potential mechanism of wild-type p53-induced phosphatase (Wip1) in cervical cancer cell line HeLa cells, along with the effect of knockdown of Wip1 in combination with gamma-irradiation on the HeLa cells. Expression of Wip1 was silenced or overexpressed. After transfection, cell viability was determined. Moreover, gamma irradiation and SB203580 were performed to explore the effect of colony formation and cell apoptosis. Likewise, protein expression levels of p38, p-p38, p53, and p p53 were assessed in the presence or not of SB203580 and overexpression of Wip1. Both the mRNA and protein levels of Wip1 were significantly decreased by transfection with Wip1-specific small interfering RNA (siRNA) but were significantly increased by transfection with pcDNA3.1-Wip1. Knockdown of Wip1 significantly decreased cell growth and colony formation ability and increased apoptotic rate. Additionally, better results were obtained by knockdown of Wip1 in combination with gamma-irradiation. The protein expression levels of p-p38 (p < 0.05), p53 (p < 0.01), and p-p53 (p < 0.05) were all significantly increased by knockdown of Wip1. However, application of SB203580 reversed the effects. Our study confirms the important roles of Wip1 in cervical cancer. Knockdown of Wip1 enhances sensitivity to radiation in HeLa cells by inhibiting cell proliferation and inducing apoptosis through activation of p38 MAPK. PMID- 26351213 TI - Loop-Mediated Isothermal Amplification as a Fast Noninvasive Method of Helicobacter pylori Diagnosis. AB - BACKGROUND: Helicobacter pylori infection is etiologically associated with some important health problems such as gastric cancer. Because of the high clinical importance of H. pylori infection, development of a noninvasive test for the detection of H. pylori is desirable. METHODS: In this study, a loop-mediated isothermal amplification (LAMP) targeted ureC of H. pylori was evaluated on 100 stool specimens and compared with a stool antigen test. Culture and rapid urease test were considered as gold standards. RESULTS: The overall detection rate of the fecal antigen test and LAMP was 58% and 82%, respectively. The analytical sensitivity of the fecal antigen test and LAMP was 500 and 10 H. pylori cells/g and 10 fg DNA/reaction, which is equal to six H. pylori genome. CONCLUSION: LAMP technique has been characterized by high sensitivity and low detection limit for the detection of H. pylori in stool specimen. Clinical diagnostic performance of LAMP was better than the stool antigen test. PMID- 26351214 TI - Does State Legislation Improve Nursing Workforce Diversity? AB - A health-care workforce representative of our nation's diversity is a health and research priority. Although racial and ethnic minorities represent 37% of Americans, they comprise only 16% of the nursing workforce. The purpose of this study was to examine the effect of state legislation on minority recruitment to nursing. Using data from the National Conference of State Legislatures, American Association of Colleges of Nursing, and U.S. census, we compared minority enrollment in baccalaureate nursing programs of states (Texas, Virginia, Michigan, California, Florida, Connecticut, and Arkansas) before and 3 years after enacting legislation with geographically adjacent states without legislation. Data were analyzed using descriptive and chi-square statistics. Following legislation, Arkansas (13.8%-24.5%), California (3.3%-5.4%), and Michigan (8.0%-10.0%) significantly increased enrollment of Blacks, and Florida (11.8%-15.4%) and Texas (11.2%-13.9%) significantly increased enrollment of Hispanic baccalaureate nursing students. States that tied legislation to funding, encouragement, and reimbursement had larger enrollment gains and greater minority representation. PMID- 26351215 TI - Exceeding the Legal Time Limits for Involuntary Mental Health Examinations: A Study of Emergency Department Delays. AB - This study addressed delays to involuntary mental health examinations experienced by individuals in emergency departments (EDs). Florida statute specifies that involuntary mental health examinations shall take place only at state-designated facilities "without unnecessary delay"-no longer than 12 h until transfer-for individuals in hospital EDs. Individuals in EDs needing involuntary mental health examinations sometimes wait for admission to inpatient units because of unavailability of mental health services. Data collectors at two hospitals reviewed the records of 170 randomly selected ED patients requiring involuntary mental health examinations. Nearly one-half (48.8%) of participants waited longer than the 12-h maximum allowed by Florida law for transfer to an authorized facility. Factors that associated with prolonged waits were being male, increased age, being a Medicare beneficiary, and being intoxicated. State agencies responsible for the regulation of hospitals and mental health facilities should use this data and engage front-line caregivers to identify statutory remedies. PMID- 26351216 TI - Challenges Associated With Using Large Data Sets for Quality Assessment and Research in Clinical Settings. AB - The rapidly expanding use of electronic records in health-care settings is generating unprecedented quantities of data available for clinical, epidemiological, and cost-effectiveness research. Several challenges are associated with using these data for clinical research, including issues surrounding access and information security, poor data quality, inconsistency of data within and across institutions, and a paucity of staff with expertise to manage and manipulate large clinical data sets. In this article, we describe our experience with assembling a data-mart and conducting clinical research using electronic data from four facilities within a single hospital network in New York City. We culled data from several electronic sources, including the institution's admission-discharge-transfer system, cost accounting system, electronic health record, clinical data warehouse, and departmental records. The final data-mart contained information for more than 760,000 discharges occurring from 2006 through 2012. Using categories identified by the National Institutes of Health Big Data to Knowledge initiative as a framework, we outlined challenges encountered during the development and use of a domain-specific data-mart and recommend approaches to overcome these challenges. PMID- 26351217 TI - Trends in Practice Patterns and Perspectives of Colorado Certified Nurse Midwives. AB - Healthcare resources are stretched perilously thin and the demand for primary healthcare services has never been greater. Despite this demand for service, relatively little is known about the practice environment of primary healthcare providers, particularly certified nurse-midwives (CNMs), where workforce surveys frequently include these specialists within the broader nurse practitioner category. A distinct professional discipline, nurse-midwives are one type of primary care provider recommended to enhance access to services. The objective of this study was to understand the nature of the nurse-midwifery practice environment in the state of Colorado. Online survey of Colorado CNMs (N = 328) found little ethnic/racial diversity and an aging workforce, with most providing care in an urban, hospital/medical center environment. Several key legislative issues were identified though respondents felt ill prepared to engage in legislative change. Overall, CNMs were optimistic about the future of midwifery and were largely satisfied with their practice. PMID- 26351218 TI - A practical clinical classification of spinal neural tube defects. AB - Current commonly used terminology to describe neural tube defects (NTD) is inconsistent, overlapping, contradictory and, at times, inaccurate making it difficult to convey the nature of the malformation and what needs to be done to optimally treat patients with these congenital abnormalities.NTD can be broadly divided into those that are open with exposed neural tissue and leaking cerebrospinal fluid (CSF) and those that are closed with no exposed neural tissue nor loss of CSF. It appears that the loss of CSF during development is the underlying factor that leads to the entire central nervous system involvement with an open NTD and lack thereof with a closed NTD, wherein only the spinal cord is malformed. There are, however, rare transitional cases that bridge the gap between the two forms.Agreeing on a nomenclature that is used in a standard fashion would be of help in addressing this group of congenital anomalies that have a great deal of variability and, at times, can be quite complex. PMID- 26351219 TI - Editorial for annual special issue on posterior fossa tumors. PMID- 26351220 TI - Posterior fossa tumors in children: developmental anatomy and diagnostic imaging. AB - INTRODUCTION: Modern understanding of the relation between the mutated cancer stem cell and its site of origin and of its interaction with the tissue environment is enhancing the importance of developmental anatomy in the diagnostic assessment of posterior fossa tumors in children. The aim of this review is to show how MR imaging can improve on the exact identification of the tumors in the brainstem and in the vicinity of the fourth ventricle in children, using both structural imaging data and a precise topographical assessment guided by the developmental anatomy. RESULTS: The development of the hindbrain results from complex processes of brainstem segmentation, ventro-dorsal patterning, multiple germinative zones, and diverse migration pathways of the neural progenitors. Depending on their origin in the brainstem, gliomas may be infiltrative or not, as well as overwhelmingly malignant (pons), or mostly benign (cervicomedullary, medullo-pontine tegmental, gliomas of the cerebellar peduncles). In the vicinity of the fourth ventricles, the prognosis of the medulloblastomas (MB) correlates the molecular subtyping as well as the site of origin: WNT MB develop from the Wnt-expressing lower rhombic lip and have a good prognosis; SHH MB develop from the Shh-modulated cerebellar cortex with an intermediate prognosis (dependent on age); recurrences are local mostly. The poor prognosis group 3 MB is radiologically heterogeneous: some tumors present classic features but are juxtaventricular (rather than intraventricular); others have highly malignant features with a small principal tumor and an early dissemination. Group 4 MB has classic features, but characteristically usually does not enhance; dissemination is common. Although there is as yet no clear molecular subgrouping of the ependymomas, their sites of origin and their development can be clearly categorized, as most develop in an exophytic way from the ventricular surface of the medulla in clearly specific locations: the obex region with expansion in the cistern magna, or the lateral recess region with expansion in the CPA and prepontine cisterns (cerebellar ependymomas, and still more intra-brainstem ependymomas are rare). Finally, almost all cerebellar gliomas are pilocytic astrocytomas. CONCLUSIONS: A developmental and anatomic approach to the posterior fossa tumors in children (together with diffusion imaging data) provides a reliable pre-surgical identification of the tumor and of its aggressiveness. PMID- 26351221 TI - Pediatric cerebellar astrocytoma: a review. AB - INTRODUCTION: Cerebellar astrocytomas (CA) are one of the most common posterior fossa tumors in children. The vast majority is low grade, and prognosis for long term survival is excellent. METHODS: Recent literature about CA was reviewed to provide an up to date overview of the epidemiology, pathology, molecular and cell biology, diagnosis, presentation, management, and long-term outcomes. RESULTS: Surgical resection remains the first-line treatment with complete removal of the tumor the goal. However, even when only subtotal resection has been achieved, there is a significant chance that the tumor will remain stable or will regress spontaneously. Adjuvant chemotherapy is reserved for those tumors that progress despite surgery, and more personalized chemotherapy is being pursued with better understanding of the molecular genetics of this tumor. Radiotherapy has generally not been recommended, but stereotactic radiotherapy and conformal proton beam radiotherapy may be reasonable options in the setting of relapse or progression. In the long term, permanent neurologic deficits, mainly cerebellar dysfunction, are common, but quality of life and cognitive function are generally good. CONCLUSIONS: Low-grade CA remains primarily a surgical disease, with excellent survival rates. Care must be taken with surgery and adjuvant treatments to preserve neurologic function to allow for optimal outcomes in the long term. PMID- 26351222 TI - Factors affecting survival of medulloblastoma in children: the changing concept of management. AB - Medulloblastoma (MB) is a type of malignant tumor arising only in the cerebellum that was first defined by Cushing and Bailey in 1920s. In this review paper, we trace the evolution of risk stratification and the correlated changing concept of management in the past years. Outcome analysis of the hospital series of the Taipei Veterans General Hospital, Cheng Hsin General Hospital, and Taipei Medical University Hospital was performed to correlate prognostic indicators with reported studies. The purpose is to provide clues for age-specific and risk adjusted optimal, effective, but beneficial and protective treatment strategies of these tumors in children. PMID- 26351223 TI - Posterior fossa ependymoma: current insights. AB - BACKGROUND: Ependymoma is the third most common malignant tumor of the posterior fossa and is a major cause of neurological morbidity and mortality in children. Current treatments, particularly surgery and external beam irradiation result in relatively poor outcomes with significant neurological and cognitive sequelae from treatment. Historical approaches have considered all ependymomas as similar entities based on their morphological appearance. RESULTS: Recent advances in genomics and epigenetics have revealed, however, that ependymomas from different CNS locations represent distinct entities. Moreover, ependymoma of the posterior fossa, the most common location in children, is actually comprised of two distinct molecular variants. These two variants have marked differences in demographics, transcriptomes, structure, methylation patterns, and clinical outcomes. This allows for the development of new biology-based clinical risk stratification, which can both prioritize patients for de-escalation of therapy and identify those who will benefit from novel therapeutic strategies. Indeed, the identification of these two variants allows an opportunity for robust preclinical modeling for development of novel therapeutic strategies. CONCLUSIONS: Herein, we have summarized our current clinical approach to diagnosis and treatment of posterior fossa ependymoma, recent advances in understanding the biology of posterior fossa ependymoma and how these new insights can be translated into the clinic to form the basis of the next generation of clinical trials. PMID- 26351224 TI - Pediatric infratentorial ganglioglioma. AB - PURPOSE: Pediatric infratentorial gangliogliomas are exceedingly rare tumors; thus, the factors affecting their outcome are poorly understood and their optimal management has still to be defined. METHODS: We reviewed the literature on pediatric gangliogliomas with a focus on those located in the posterior fossa to study treatment and outcome data. We added to this review some of our clinical cases. RESULTS: We found 100 and 80 cases of brainstem and cerebellar pediatric ganglioglioma, respectively, in our literature review. The surgical management varied from biopsy to gross total resection, and adjuvant treatment was given after incomplete resection or at time of progression. A gross total resection should be attempted to remove the contrast enhancing part of the tumor, which may be possible in most of the cerebellar gangliogliomas and some of the brainstem lesions. The cervicomedullary ganglioglioma seems to be the most infiltrative and least amenable to complete resection. Chemotherapy has a limited role and BRAF mutation was reported in 38 to 54 % of cases. The use of radiotherapy exposes the patient to a risk of malignant transformation and should be reserved for unresectable tumors which progress. CONCLUSION: Pediatric posterior fossa gangliogliomas are rare and challenging tumors due to their frequent infiltrative component involving the brainstem. To date, adjuvant therapy has a limited role that may evolve with time thanks to the use of targeted therapies against BRAF mutation. The surgical resection of well-defined contrast enhancing parts should be attempted even in staged surgeries and balanced with the risks of neurological deterioration. PMID- 26351225 TI - Atypical teratoid rhabdoid tumors of the posterior fossa in children. AB - PURPOSE: Atypical teratoid rhabdoid tumors (AT/RT) are rare, aggressive, central nervous system neoplasms that typically affect children under 3 years of age and have a very poor prognosis. Early case series consistently demonstrated rapid recurrence with progression to death, but more recent experience has shown significant improvements in progression free and overall survival. METHODS: A retrospective analysis of the clinical data of children diagnosed with AT/RT at the Ann & Robert H. Lurie Children's Hospital of Chicago (formerly Children's Memorial Hospital) between 2000 and 2014 was performed. Overall survival (OS) was used to describe outcome. Our small sample size and the utilization of different adjuvant regimens over the study period precluded a detailed statistical analysis. RESULTS: Eight children with AT/RT of the posterior fossa were included in our report. Gross total resection (GTR) was achieved in five children (63 %), two children underwent subtotal resection (25 %), and there was one who underwent biopsy. Patients were treated with various combinations of chemotherapy with or without conformal radiation therapy (RT). Median overall survival was 5 months (range 1 to 107 months) with two patients achieving sustained responses to 45 and 107 months. CONCLUSIONS: Our experience is in line with prior reports that show that children diagnosed with AT/RT of the posterior fossa have a poor prognosis, but that long-term survival is possible. These tumors provide many challenges, but contemporary series are beginning to show improvements in survival. PMID- 26351226 TI - Uncommon pediatric tumors of the posterior fossa: pathologic and molecular features. AB - INTRODUCTION: Three tumors are commonly encountered in the posterior fossa of children: pilocytic astrocytoma (PA), medulloblastoma (MB), and ependymoma. However, a variety of additional tumors may occasionally be appreciated. Appropriate and successful treatment of these less common cases is predicated upon correct pathologic diagnosis. METHODS/RESULTS: Reviewed herein are five less common tumors that may affect the posterior fossa of children: (1) "embryonal tumor with multilayered rosettes" (ETMR); (2) "cribriform neuroepithelial tumor" (CRINET); (3) "rosette-forming glioneuronal tumor" (RGNT); (4) "diffuse pilocytic astrocytoma" (dPA); and, (5) "desmoplastic small round cell tumor" (DSRCT). Each of the foregoing has a varying predilection for children and a posterior fossa location. For example, RGNT by definition arises in association with the 4th ventricle; while the mean age of those afflicted is 33, children may also be affected. Likewise, descriptions of dPA are generally restricted to the posterior fossa, and in particular, the cerebellum of children. Alternatively, DSRCT is a form of undifferentiated sarcoma that characteristically originates in the abdomen of children, but on occasion arises from the tentorium of young adults and children. The relevant molecular genetic underpinnings for each of the tumors highlighted herein have been well described and may carry diagnostic utility, not to mention clues as to underlying etiology. CONCLUSION: A number of pediatric brain tumors have a tendency to occur in the posterior fossa. While far less common than PA, MB, or ependymoma, the entities highlighted herein appear to have a degree of proclivity for the posterior fossa of children and as such warrant due consideration in the clinicopathologic workup of these cases. PMID- 26351227 TI - Cerebellopontine angle tumors in infants and children. AB - OBJECTIVE: Cerebellopontine angle (CPA) and cerebellomedullary fissure (CMF) tumors are rare in children and information is scarce in the literature. This retrospective study reports their histological distribution and tumor origin, and describes surgical resections and post-operative outcome based upon the authors' consecutive personal series. METHODS: Clinical data of infants and children 16 years old or younger of age treated from 2001 to 2012 by a single surgeon was retrospectively reviewed. All had histologically verified CPA/CMF tumors and underwent radical tumor resection through craniotomy except for two children who had a stereotactic biopsy for malignant tumors (glioblastoma and primitive neuroectodermal tumor (PNET)). Tumors' pathological distributions, tumors' origin, surgical approaches, and patients' outcome were reviewed. RESULTS: There were 44 infants and children with the age at diagnosis ranging from 11 weeks to 16 years; 32 were predominantly in the CPA and/or CMF whereas 12 showed an extension to the fourth ventricle. Pathology showed 14 ependymomas, 12 benign gliomas (11 pilocytic astrocytomas, 1 ganglioglioma), 4 atypical teratoid rhabdoid tumors (ATRTs), 4 epidermoids, 3 primitive neuroectodermal tumors (PNETs), 3 meningiomas, 3 nerve sheath tumors, and 1 glioblastoma. The anatomical site of tumor origin was the lateral recess of the fourth ventricle in 13 patients, the ventral cerebellar hemisphere in 8, the cerebellar peduncle in 7, and the brain stem in 6. Others were from embryonal nest, cranial nerve, or meninges. For 42 tumor resections, 38 were approached through a posterior fossa craniotomy and 4 through a temporal craniotomy and transtentorial approach. At tumor resection, 26 had a gross total or near total resection, 12 subtotal resection, and 4 partial resection. There were no mortalities. The most significant morbidity was ninth and tenth nerve palsy; 15 patients had unilateral vocal cord palsy or dysphagia. Of these, nine were treated with nasogastric (NG) feeding tube, five with a combination of gastrostomy (G-tube) and tracheotomy, and one with G-tube. All had successful removal of NG feeding from 1 month to 2 years (average 6 months). The tracheostomy and G-tube were removed between 4 months and 2 years (average 14 months) in all. CONCLUSION: A plethora of tumor types occur in childhood at the CPA/CMF and our review indicated 50 % were benign in histology. High rates of lower cranial nerve morbidity were experienced but their dysfunctions were often recovered or compensated in 2 years. However, one should be cognizant of these complications and conduct resection with appropriate surgical approach, intraoperative monitoring, and surgical microscope. PMID- 26351228 TI - Posterior fossa tumors in infants and neonates. AB - INTRODUCTION: Management of posterior fossa tumors in infants and neonates is challenging. The characteristics of the young babies make surgery very difficult, sometimes precluding a safe complete removal. METHODS: A review of the literature was undertaken to examine the incidence, histology, surgical aspects, and prognosis of posterior fossa tumors in the first year of life. Therapeutical strategies of the most frequent tumor types are also discussed in detail. RESULTS: Histology is dominated by tumors with aggressive behavior, such as medulloblastomas, atypical teratoid/rhabdoid tumors, and anaplastic ependymomas. The most important surgical considerations in small children are the small circulating blood volume; the poor thermoregulation; and incomplete maturation of the brain, of the skull, and of the soft tissue. Treatment toxicity is inversely related to the age of the patients. Radiation therapy is usually considered as contraindicated in young children, with few exceptions. Proton therapy is a promising tool, but access to this kind of treatment is still limited. The therapeutic limitations of irradiation render resection of this tumor and adjuvant chemotherapy often the only therapeutic strategy in many cases. CONCLUSIONS: The overall prognosis remains dismal because of the prevalent aggressive histologies, the surgical challenges, and the limitations of adjuvant treatment. Nevertheless, the impressive improvements in anesthesiology and surgical techniques allow, in the vast majority of the cases, complete removal of the lesions with minor sequelae in high-volume referral pediatric centers. PMID- 26351229 TI - Biopsy in a series of 130 pediatric diffuse intrinsic Pontine gliomas. AB - PURPOSE: Diffuse intrinsic pontine glioma (DIPG) is the most severe pediatric solid tumor, with no significant improvement in the past 50 years. Possible reasons for failure to make therapeutic progress include poor understanding of the underlying molecular biology due to lack of tumor material. METHODS: We performed a prospective analysis of children with typical appearance of DIPG who had a stereotactic biopsy in our unit since 2002. Technical approach, complications, histopathological results, and samples processing are exposed. The literature on this subject is discussed. RESULTS: Reviewing our own 130 cases of DIPG biopsies and previous published data, these procedures appear to have a diagnostic yield and morbidity rates similar to those reported for other brain locations (3.9 % of transient morbidity in our series). In addition, the quality and the quantity of the material obtained allow to (1) confirm the diagnosis, (2) reveal that WHO grading was useless to predict outcome, and (3) perform an extended molecular screen, including biomarkers study and the development of preclinical models. Recent studies reveal that DIPG may comprise more than one biological entity and a unique oncogenesis involving mutations never described in other types of cancers, i.e., histones H3 K27M and activin receptor ACVR1. CONCLUSION: Stereotactic biopsies of DIPG can be considered as a safe procedure in well-trained neurosurgical teams and could be incorporated in protocols. It is a unique opportunity to integrate DIPG biopsies in clinical practice and use the biology at diagnosis to drive the introduction of innovative targeted therapies, in combination with radiotherapy. PMID- 26351230 TI - Management of posterior fossa tumors and hydrocephalus in children: a review. AB - OBJECT: Most pediatric patients that present with a posterior fossa tumor have concurrent hydrocephalus. There is significant debate over the best management strategy of hydrocephalus in this situation. The objectives of this paper were to review the pathophysiology model of posterior fossa tumor hydrocephalus, describe the individual risks factors of persistent hydrocephalus, and discuss the current management options. Specifically, the debate over preresection cerebrospinal fluid diversion is discussed. RESULTS: Only 10-40 % demonstrate persistent hydrocephalus after posterior fossa tumor resection. It appears that young age, moderate to severe hydrocephalus, transependymal edema, the presence of cerebral metastases, and tumor pathology (medulloblastoma and ependymoma) on presentation predict postresection or persistent hydrocephalus. The Canadian Preoperative Prediction Rule for Hydrocephalus (CPPRH), a validated prediction model, can be used to stratify patients at point of first contact into high and low risk for persistent hydrocephalus. CONCLUSIONS: A protocol is proposed for managing hydrocephalus that utilizes the CPPRH. Low-risk patients can be monitored conservatively with or without an intraoperative extraventricular drain, while high-risk patients require the use of an intraoperative extraventricular drain, higher postoperative hydrocephalus surveillance, and even consideration for a preoperative endoscopic third ventriculostomy. PMID- 26351232 TI - Surgical approaches to IV ventricle--anatomical study. AB - PURPOSE: Knowledge of anatomy of the IV ventricle is basic to surgical approach of any kind of lesion in its compartment as well as for those located in its neighborhood. The purpose of this study is to demonstrate the surgical approach options for the IV ventricle, based on the step by step dissection of anatomical specimens. METHODS: Fifty formalin-fixed specimens provided were the material for this study. The dissections were performed in the microsurgical laboratory in Gainesville, Florida, USA. RESULTS: The IV ventricle in a midline sagittal cut shows a tent-shaped cavity with its roofs pointing posteriorly and the floor formed by the pons and the medulla. The superior roof is formed by the superior cerebellar peduncles laterally and the superior medullary velum on the midline. The inferior roof is formed by the tela choroidea, the velum medullary inferior, and the nodule. The floor of the IV ventricle has a rhomboid shape. The rostral two thirds are related to the pons, and the caudal one third is posterior to the medulla. The median sulcus divides the floor in symmetrical halves. The sulcus limitans runs laterally to the median sulcus, and the area between the two sulci is called the median eminence. The median eminence contains rounded prominence related to the cranial nucleus of facial, hypoglossal, and vagal nerves. The lateral recesses are extensions of the IV ventricle that opens into the cerebellopontine cistern. The cerebellomedullary fissure is a space between the cerebellum and the medulla and can be used as a surgical corridor to the IV ventricle. CONCLUSIONS: We obtained in this study a didactic dissection of the different anatomical structures, whose recognition is important for addressing the IV ventricle lesions. PMID- 26351231 TI - Intraoperative neurophysiology in posterior fossa tumor surgery in children. PMID- 26351233 TI - Surgical approaches for brainstem tumors in pediatric patients. AB - PURPOSE: To analyze the pathways to brainstem tumors in childhood, as well as safe entry zones. METHOD: We conducted a retrospective study of 207 patients less than 18 years old who underwent brainstem tumor resection by the first author (Cavalheiro, S.) at the Neurosurgical Service and Pediatric Oncology Institute of the Sao Paulo Federal University from 1991 to 2011. RESULTS: Brainstem tumors corresponded to 9.1 % of all pediatric tumors operated in that same period. Eleven previously described "safe entry zones" were used. We describe a new safe zone located in the superior ventral pons, which we named supratrigeminal approach. The operative mortality seen in the first 2 months after surgery was 1.9 % (four patients), and the morbidity rate was 21.2 %. CONCLUSIONS: Anatomic knowledge of intrinsic and extrinsic brainstem structures, in association with a refined neurosurgical technique assisted by intraoperative monitoring, and surgical planning based on magnetic resonance imaging (MRI) and tractography have allowed for wide resection of brainstem lesions with low mortality and acceptable morbidity rates. PMID- 26351234 TI - Cerebellar mutism. AB - INTRODUCTION: Cerebellar mutism (CM) is defined as a peculiar form of mutism that may complicate the surgical excision of posterior cranial fossa tumor. The incidence is variable in the literature, occurring in up to one third of cases in some series. Commonly occurring peculiar features of CM are delayed onset following surgery, limited duration, and spontaneous recovery usually associated with dysarthria. METHODS: A review has been performed concerning anatomical substrates and circuits actually considered to be involved in the development of cerebellar mutism, as well as risk factors for its development that have been documented in the literature. Attention has also been given to the long-term prognosis and the possibilities of rehabilitation that can be considered in these children, which has been compared with the authors' institutional experience. RESULTS AND CONCLUSIONS: Tumor infiltration of the brainstem seems to represent the most relevant feature related to the development of CM, along with the histological diagnosis of medulloblastoma. On the other hand, hydrocephalus does not represent an independent risk factor. The higher rate of CM in children seems to be related to the higher incidence in children of tumors with malignant histology and brain stem involvement. Surgical technique does not seem to have a definite role; in particular, the use of a telovelar approach as compared to vermian split to reach the fourth ventricle extension of the tumor has not been demonstrated to prevent the development of cerebellar mutism. Concerning long term prognosis, around one third of the children who develop cerebellar mutism after surgery have a persistent dysarthria, the remaining ones showing a residual phonological impairment. Long-term dysarthric features tend to be more severe and less prone to recovery in children presenting at diagnosis with associated combined procedural memory and defective neurocognitive functions. PMID- 26351235 TI - Posterior fossa syndrome following brain tumour resection: review of pathophysiology and a new hypothesis on its pathogenesis. AB - INTRODUCTION: Posterior fossa syndrome (PFS), also known as cerebellar mutism syndrome (CMS), is a severe complication affecting children following surgery for posterior fossa brain tumours. Its incidence varies between 8 and 31 %, and its exact pathogenesis remains unclear. In this article, we aim to review the existing theories on its pathogenesis and propose a new hypothesis. DISCUSSION: There is varying level of evidence on existing theories on the pathogenesis of PFS following surgery. These include cerebellar perfusion deficits due to vasospasm, oedema or axonal injury due to direct surgical injury and neuronal dysfunction. There is emerging evidence that interruption of the dentato-thalamo cortical (DTC) pathway is responsible for PFS. Based on our experience with intraoperative MRI, radiological and pathological evidence on heat-related brain injury, we propose a new hypothesis implicating thermal injury resulting from the use of the Cavitron Ultrasonic Aspirator (CUSA) as an important mechanism in the pathogenesis of PFS. CONCLUSION: The pathogenesis of PFS is likely to be multifactorial with direct injury from surgery being a major factor. We believe that thermal injury in addition to mechanical injury to the proximal segment of the DTC plays an important role in the pathogenesis of PFS and should be considered in future research related to the aetiology, prevention and management of PFS. PMID- 26351236 TI - A systematic review of neuropsychological outcomes following posterior fossa tumor surgery in children. AB - PURPOSE: Central nervous system tumors are the most common solid tumors in the pediatric population. As children with central nervous system (CNS) tumors are surviving into adolescence and adulthood, more research is being focused on the long-term cognitive outcomes of the survivors. This review examines the literature on different cognitive outcomes of survivors of different childhood posterior fossa CNS tumor types. METHODS: The authors reviewed the literature for articles published from 2000 to 2012 about long-term neuropsychological outcomes of children diagnosed with posterior fossa brain tumors before the age of 18, which distinguished between histological tumor types, and had a minimum follow-up of 3 years. RESULTS: The literature search returned 13 articles, and a descriptive analysis was performed comparing intelligence quotient (IQ), attention/executive function, and memory components of 456 survivors of childhood posterior fossa tumors. Four articles directly compared astrocytoma and medulloblastoma survivors and showed medulloblastoma survivors fared worse in IQ, attention/executive function, and memory measurements. Five articles reporting medulloblastomas found IQ, attention, and memory scores to be significantly below the standardized means. Articles examining astrocytoma survivors found IQ scores within the normal range for the population. Survivors of ependymomas reported 2/23 survivors impaired on IQ scores, while a second study reported a significant number of ependymoma survivors lower than the expected population norm. CONCLUSIONS: Tumor histopathology and the type of postoperative adjuvant therapy seem to have a significant impact on the long-term neuropsychological complications of pediatric posterior fossa CNS tumor survivors. Age at diagnosis and treatment factors are important variables that affect the outcomes of the survivors. PMID- 26351237 TI - Functional and neuropsychological late outcomes in posterior fossa tumors in children. AB - Tumors of the posterior fossa (PF) account for up to 60 % of all childhood intracranial tumors. Over the last decades, the mortality rate of children with posterior fossa tumors has gradually decreased. While survival has been the primary objective in most reports, quality of survival increasingly appears to be an important indicator of a successful outcome. Children with a PF tumor can sustain damage to the cerebellum and other brain structures from the tumor itself, concomitant hydrocephalus, the consequences of treatment (surgery, chemotherapy, radiotherapy), or a combination of these factors. Together, these contribute to long-term sequelae in physical functioning, neuropsychological late outcomes (including academic outcome, working memory, perception and estimation of time, and selective attention, long-term neuromotor speech deficits, and executive functioning). Long-term quality of life can also be affected by endocrinological complication or the occurrence of secondary tumors. A significant proportion of survivors of PF tumors require long-term special education services and have reduced rates of high school graduation and employment. Interventions to improve neuropsychological functioning in childhood PF tumor survivors include (1) pharmacological interventions (such as methylphenidate, modafinil, or donepezil), (2) cognitive remediation, and (3) home-based computerized cognitive training. In order to achieve the best possible outcome for survivors, and ultimately minimize long-term complications, new interventions must be developed to prevent and ameliorate the neuro-toxic effects experienced by these children. PMID- 26351239 TI - The influence of distal screw length on the primary stability of volar plate osteosynthesis--a biomechanical study. AB - BACKGROUND: Extensor tendon irritation is one of the most common complications following volar locking plate osteosynthesis (VLPO) for distal radius fractures. It is most likely caused by distal screws protruding the dorsal cortex. Shorter distal screws could avoid this, yet the influence of distal screw length on the primary stability in VLPO is unknown. The aim of this study was to compare 75 to 100% distal screw lengths in VLPO. METHODS: A biomechanical study was conducted on 11 paired fresh-frozen radii. HRpQCT scans were performed to assess bone mineral density (BMD) and bone mineral content (BMC). The specimens were randomized pair-wise into two groups: 100% (group A) and 75% (group B) unicortical distal screw lengths. A validated fracture model for extra-articular distal radius fractures (AO-23 A3) was used. Polyaxial volar locking plates were mounted, and distal screws was inserted using a drill guide block. For group A, the distal screw tips were intended to be flush or just short of the dorsal cortex. In group B, a target screw length of 75% was calculated. The specimens were tested to failure using a displacement-controlled axial compression test. Primary biomechanical stability was assessed by stiffness, elastic limit, and maximum force as well as with residual tilt, which quantified plastic deformation. RESULTS: Nine specimens were tested successfully. BMD and BMC did not differ between the two groups. The mean distal screw length of group A was 21.7 +/- 2.6 mm (range: 16 to 26 mm), for group B 16.9 +/- 1.9 mm (range: 12 to 20 mm). Distal screws in group B were on average 5.6 +/- 0.9 mm (range: 3 to 7 mm) shorter than measured. No significant differences were found for stiffness (706 +/- 103 N/mm vs. 660 +/- 124 N/mm), elastic limit (177 +/- 25 N vs. 167 +/- 36 N), maximum force (493 +/- 139 N vs. 471 +/- 149 N), or residual tilt (7.3 degrees +/- 0.7 degrees vs. 7.1 degrees +/- 1.3 degrees ). CONCLUSION: The 75% distal screw length in VLPO provides similar primary stability to 100% unicortical screw length. This study, for the first time, provides the biomechanical basis to choose distal screws significantly shorter then measured. PMID- 26351240 TI - Erratum to: A donor thrombomodulin gene variation predicts graft-versus-host disease development and mortality after bone marrow transplantation. PMID- 26351241 TI - From maternity paper hand-held records to electronic health records: what do women tell us about their use? AB - The paper hand-held record (PHR) has been used extensively in general practice (GP) shared care management of pregnant women, and recently, the first Mater Shared Electronic Health Record (MSEHR) was introduced. The aim of this qualitative study was to examine women's experiences using the records and the contribution of the records to integrate care. At the 36-week antenatal visit in a maternity tertiary centre clinic, women were identified as a user of either the PHR or the MSEHR and organised into Phase 1 and Phase 2 studies respectively. Fifteen women were interviewed in Phase 1 and 12 women in Phase 2. Semi structured interviews were used for data collection, and analysed using qualitative content analysis. Four main themes were identified: (1) purpose of the record, (2) perceptions of the record; (3) content of the record, and (4) sharing the record. Findings indicate that the PHR is a well-liked maternity tool. The findings also indicate there is under-usage of the MSEHR due to health care providers failing to follow up and discuss the option of using the electronic health record option or if a woman has completed the log-in process. This paper adds to an already favourable body of knowledge about the use of the PHR. It is recommended that continued implementation of the MSEHR be undertaken to facilitate its use. PMID- 26351243 TI - Sex steroid hormone secretion in the wall lizard Podarcis sicula testis: The involvement of VIP. AB - Vasoactive intestinal peptide (VIP) is a pleiotropic neuropeptide involved in different functions, including testosterone synthesis. Recently, we reported the presence of VIP in the testis of Podarcis sicula, throughout the reproductive cycle. Now, we investigated the effects of the VIP on steroidogenesis in significant periods of the Podarcis reproductive cycle: winter stasis, reproductive period, and summer stasis. Using VIP treatments in testis culture in absence or presence of receptors antagonists, we demonstrated for the first time that in P. sicula, VIP is involved not only in testosterone synthesis, as in mammals, but in 17beta-estradiol synthesis too. J. Exp. Zool. 323A: 714-721, 2015. (c) 2015 Wiley Periodicals, Inc. PMID- 26351242 TI - Supracolloidal Architectures Self-Assembled in Microdroplets. AB - We demonstrate a novel method for the formation of a library of structured colloidal assemblies by exploiting the supramolecular heteroternary host-guest interaction between cucurbit[8]uril (CB[8]) and methyl viologen- and naphthalene functionalised particles. The approach is dependent upon compartmentalisation in microdroplets generated by a microfluidic platform. Though the distribution of colloidal particles encapsulated within each microdroplet followed a Poisson distribution, tuning the concentration of the initial colloidal particle suspensions provided some level of control over the structure of the formed colloidal assemblies. This ability to direct the assembly of complementarily functionalised colloids through a supramolecular interaction, without the need for complex modification of the colloidal surface or external stimuli, presents an exciting new approach towards the design of structured colloidal materials with the potential to produce many challenging structures. PMID- 26351244 TI - Engineering Rieske Non-Heme Iron Oxygenases for the Asymmetric Dihydroxylation of Alkenes. AB - The asymmetric dihydroxylation of olefins is of special interest due to the facile transformation of the chiral diol products into valuable derivatives. Rieske non-heme iron oxygenases (ROs) represent promising biocatalysts for this reaction as they can be engineered to efficiently catalyze the selective mono- and dihydroxylation of various olefins. The introduction of a single point mutation improved selectivities (>=95 %) and conversions (>99 %) towards selected alkenes. By modifying the size of one active site amino acid side chain, we were able to modulate the regio- and stereoselectivity of these enzymes. For distinct substrates, mutants displayed altered regioselectivities or even favored opposite enantiomers compared to the wild-type ROs, offering a sustainable approach for the oxyfunctionalization of a wide variety of structurally different olefins. PMID- 26351245 TI - Obligations of low income countries in ensuring equity in global health financing. AB - BACKGROUND: Despite common recognition of joint responsibility for global health by all countries particularly to ensure justice in global health, current discussions of countries' obligations for global health largely ignore obligations of developing countries. This is especially the case with regards to obligations relating to health financing. Bearing in mind that it is not possible to achieve justice in global health without achieving equity in health financing at both domestic and global levels, our aim is to show how fulfilling the obligation we propose will make it easy to achieve equity in health financing at both domestic and international levels. DISCUSSION: Achieving equity in global health financing is a crucial step towards achieving justice in global health. Our general view is that current discussions on global health equity largely ignore obligations of Low Income Country (LIC) governments and we recommend that these obligations should be mainstreamed in current discussions. While we recognise that various obligations need to be fulfilled in order to ultimately achieve justice in global health, for lack of space we prioritise obligations for health financing. Basing on the evidence that in most LICs health is not given priority in annual budget allocations, we propose that LIC governments should bear an obligation to allocate a certain minimum percent of their annual domestic budget resources to health, while they await external resources to supplement domestic ones. We recommend and demonstrate a mechanism for coordinating this obligation so that if the resulting obligations are fulfilled by both LIC and HIC governments it will be easy to achieve equity in global health financing. Although achieving justice in global health will depend on fulfillment of different categories of obligations, ensuring inter- and intra-country equity in health financing is pivotal. This can be achieved by requiring all LIC governments to allocate a certain optimal per cent of their domestic budget resources to health while they await external resources to top up in order to cover the whole cost of the minimum health opportunities for LIC citizens. PMID- 26351246 TI - Minorities' acculturation and social adjustment: The moderator role of meta perceptions of majority's acculturation attitudes. AB - Two studies addressed the role of Black meta-perception of acculturation attitudes on the relation between minority acculturation attitudes and their social adjustment (school achievement and perceived quality of intergroup relations). Participants in both studies were Black Lusophone adolescents living in Portugal. Study 1 (N = 140) indicated that participants' attitude regarding the host culture was positively correlated with their school achievement and to their evaluation of intergroup relations. It also indicated that participants' meta-perception of majority attitude add to the explained variance of participants' social adjustment. Study 2 (N = 62) manipulated the perceived majority high/low support of immigrants' learning the host culture. The dependent variable (DV) was perceived quality of intergroup relations. Only in the low support condition were participants' attitudes towards the host culture positively related to perceived quality of Black-White relationships. These results suggest that perceived social context is central to understand the relationship between minority adolescents' acculturation attitudes and key dimensions of their adjustment to host societies. PMID- 26351247 TI - Differences of Mortality Rates between Pocket and Nonpocket Cardiovascular Implantable Electronic Device Infections. AB - BACKGROUND: A steady rise in the use of cardiovascular implantable electronic devices (CIEDs), particularly in the elderly, has led to an increase in device related infections. Although often studied and reported as a single entity, these complications in fact comprise a heterogeneous group. Specific subgroups may be associated with distinct mortality risks. METHODS: Medical records of all patients who underwent device extraction for CIED-related infection at a single tertiary referral center between 1991 and 2007 were reviewed. Infections were divided into four subgroups: primary pocket site infection (PPSI), pocket site infection with bacteremia, primary/isolated bacteremia (PIB), and device-related infective endocarditis (DRIE). Clinical presentation, laboratory data, and mortality rates were obtained by chart review and by querying the Social Security Death Index. RESULTS: A total of 387 cases were analyzed. The overall in-hospital and 1-year all-cause mortality rates were 7.2% and 25.3%, respectively. Patients with PIB or DRIE had significantly higher mortality rates (hazard ratio [HR] 2.3; 95% confidence interval [CI] 1.2-4.6 and HR 2.5; 95% CI 1.6-4.1, respectively) when compared with patients in the PPSI group. Patients who did not receive a new device during the initial admission also had a higher 1-year mortality rate compared to those who did (HR 2.7; 95% CI 1.8-4.1). CONCLUSIONS: Our patients with CIED-related infections requiring extraction/hospitalization had a significant mortality risk. Presence of pocket site infection carried a more favorable prognosis, regardless of the presence of bacteremia. Early detection and prevention of CIED-related infections with PIB (i.e., no pocket site involvement), especially for high-risk populations, is needed. PMID- 26351248 TI - Just What the Doctor Ordered? Physician Participation in Health Care Organization Corporate Boards. PMID- 26351249 TI - Measuring Gastrointestinal Electrical Activity With Extracellular Electrodes. PMID- 26351250 TI - Temporary Endoscopic Stimulation in Gastroparesis-like Syndrome. AB - BACKGROUND/AIMS: Gastroparesis-like syndrome (GLS) is defined as gastroparesis like symptoms with normal gastric scintigraphy. While the efficacy of gastric electrical stimulation (GES) in gastroparesis is well known, the utility of GES in GLS is largely unknown. Our aim was to clarify the role of GES in GLS. We implanted consecutive patients with symptoms of gastroparesis with temporary gastric electrical stimulation and observed changes in gastric scintigraphy and total symptom score. METHODS: Five hundred and fifty-one patients suffering from symptoms of gastroparesis (nausea, vomiting, bloating/distension, anorexia/early satiety, and abdominal pain) with negative endoscopy underwent gastric scintigraphy with analysis of 1) solid radionuclide gastric emptying at 1, 2, and 4 hours (% remaining); 2) area under the gastric emptying curve (AUC) at 1, 2, and 4 hours; and 3) total gastric emptying test (GET) (the sum of 1, 2, and 4 hour values). Patients were stratified into: delayed gastric emptying, normal gastric emptying, and rapid gastric emptying (Appendix). Of the 551 patients in the larger cohort, 379 had implantation of temporary gastric electrical stimulation (tGES). Gastrointestinal symptoms and gastric emptying were com - pared pre and post tGES implantation. RESULTS: After tGES, 2 hour gastric retention decreased (P < 0.01) for the delayed patients, and increased (P < 0.001) for normal and rapid patients. These changes were accompanied by improvements (P < 0.001) in vomiting, nausea, and total symptom scores in all 3 subgroups. CONCLUSIONS: Gastric electrical stimulation may be an effective therapy for treating the symptoms of gastroparesis with normal gastric emptying. Further exploration of endoscopic electrical stimulation as a treatment for gastroparesis-like symptoms with non-delayed gastric emptying is needed. PMID- 26351251 TI - Small Intestinal Bacterial Overgrowth Diagnosed by Glucose Hydrogen Breath Test in Post-cholecystectomy Patients. AB - BACKGROUND/AIMS: Patients undergoing cholecystectomy may have small intestinal bacterial overgrowth (SIBO). We investigated the prevalence and characteristics of SIBO in patients with intestinal symptoms following cholecystectomy. METHODS: Sixty-two patients following cholecystectomy, 145 with functional gastrointestinal diseases (FGIDs), and 30 healthy controls undergoing hydrogen (H2)-methane (CH4) glucose breath test (GBT) were included in the study. Before performing GBT, all patients were interrogated using bowel symptom questionnaire. The positivity to GBT indicating the presence of SIBO, gas types and bowel symptoms were surveyed. RESULTS: Post-cholecystectomy patients more often had SIBO as evidenced by a positive (+) GBT than those with FGID and controls (29/62, 46.8% vs 38/145, 26.2% vs 4/30, 13.3%, respectively; P = 0.010). In the gas types, the GBT (H2) + post-cholecystectomy patients was significantly higher than those in FGIDs patients (P = 0.017). Especially, positivity to fasting GBT (H2) among the GBT (H2)+ post-cholecystectomy patients was high, as diagnosed by elevated fasting H2 level. The GBT+ group had higher symptom scores of significance or tendency in abdominal discomfort, bloating, chest discomfort, early satiety, nausea, and tenesmus than those of the GBT negative group. The status of cholecystectomy was the only significant independent factor for predicting SIBO. CONCLUSIONS: The SIBO with high levels of baseline H2 might be the important etiologic factor of upper GI symptoms for post-cholecystectomy patients. PMID- 26351252 TI - The Bitter Taste Receptor Agonist Quinine Reduces Calorie Intake and Increases the Postprandial Release of Cholecystokinin in Healthy Subjects. AB - BACKGROUND/AIMS: Bitter taste receptors are expressed throughout the digestive tract. Data on animals have suggested these receptors are involved in the gut hormone release, but no data are available in humans. Our aim is to assess whether bitter agonists influence food intake and gut hormone release in healthy subjects. METHODS: Twenty healthy volunteers were enrolled in a double-blind cross-over study. On 2 different days, each subject randomly received an acid resistant capsule containing either placebo or 18 mg of hydrochloride (HCl) quinine. After 60 minutes, all subjects were allowed to eat an ad libitum meal until satiated. Plasma samples were obtained during the experiment in order to evaluate cholecystokinin (CCK) and ghrelin levels. Each subject was screened to determine phenylthiocarbamide (PTC) tasting status. RESULTS: Calorie intake was significantly lower when subjects received HCl quinine than placebo (514 +/- 248 vs 596 +/- 286 kcal; P = 0.007). Significantly higher CCK DeltaT90 vs T0 and DeltaT90 vs T60 were found when subjects received HCl quinine than placebo (0.70 +/- 0.69 vs 0.10 +/- 0.86 ng/mL, P = 0.026; 0.92 +/- 0.75 vs 0.50 +/- 0.55 ng/mL, P = 0.033, respectively). PTC tasters ingested a significantly lower amount of calories when they received HCl quinine compared to placebo (526 +/- 275 vs 659 +/- 320 kcal; P = 0.005), whereas no significant differences were found for PTC non-tasters (499 +/- 227 vs 519 +/- 231 kcal; P = 0.525). CONCLUSIONS: This study showed that intra-duodenal release of a bitter compound is able to significantly affect calorie intake and CCK release after a standardized meal. Our results suggest that bitter taste receptor signaling may have a crucial role in the control of food intake. PMID- 26351254 TI - A More In-depth Evaluation of Impedance-pH Could Assist in Distinguishing Reflux related From Reflux-unrelated Heartburn. PMID- 26351253 TI - Probiotic Therapy of the Irritable Bowel Syndrome: Why Is the Evidence Still Poor and What Can Be Done About It? AB - BACKGROUND/AIMS: Despite numerous randomized clinical trials and meta-analyses, there is no increased evidence for the efficacy of probiotics in the treatment of irritable bowel syndrome (IBS). We review this evidence, identify and analyse the reasons for this lack of evidence and propose methodological improvements for future studies. METHODS: Based on a literature search, we identified 56 papers that matched the purpose of our analyses. Twenty-seven studies used multi-species bacterial preparations and 29 used single-strain probiotics. They were analysed regarding patients included, treatment duration, probiotic dosage, and outcome measures. RESULTS: Trials in both groups suffered from heterogeneity with respect to probiotic concentration, duration of treatment, and other methodological issues (crossover design and underpowered studies). This heterogeneity did not allow the application of a meta-analytic approach and a systematic review was therefore performed instead. Multi-strain preparations combined 2 to 8 different bacterial subspecies, mostly lactobacilli or bifidobacteria, and used variable lengths of treatments. Overall, more than 50% of trials presented negative outcomes. The majority of the single-strain probiotic trials employing lactobacilli or Saccharomyces were negative, whereas trials employing bifidobacteria showed positive results. CONCLUSIONS: The heterogeneity of the studies of probiotics in IBS questions the value of meta-analyses. The use of different bacterial strains and different mixtures of these strains, as well as different dosages, are the main contributors to this heterogeneity. Current data provides limited evidence for the efficacy of a small number of single-strain probiotics in IBS (mostly bifidobacteria) and sound studies following strict trial guidelines (Food and Drug Administration and European Medicines Agency guidelines for clinical trials) are needed. We summarised and proposed some methodological issues for future studies in the field. PMID- 26351255 TI - Assessing the risk to green sturgeon from application of imidacloprid to control burrowing shrimp in Willapa Bay, Washington--Part II: controlled exposure studies. AB - The activities of 2 species of burrowing shrimp have a negative impact on the growth and survival of oysters reared on intertidal mudflats in Willapa Bay and Grays Harbor, Washington (USA). To maintain viable harvests, oyster growers proposed the application of the neonicotinoid insecticide imidacloprid onto harvested beds for the control of burrowing shrimp. In test applications, water column concentrations of imidacloprid were relatively low and dissipated rapidly. The foraging activities of the green sturgeon (listed in the US Endangered Species Act) could result in exposure to higher, more sustained imidacloprid concentrations within sediment porewater and from the consumption of contaminated shrimp. Controlled experiments were conducted using surrogate white sturgeon to determine acute and chronic effect concentrations, to examine overt effects at more environmentally realistic concentrations and durations of exposure, and to assess chemical depuration. The 96-h median lethal concentration was 124 mg L(-1) , and the predicted 35-d no-observed-adverse-effect concentration was 0.7 mg L( 1) . No overt effects were observed following environmentally relevant exposures. Imidacloprid half-life in plasma was greater than 32 h. Measured concentrations of imidacloprid in porewater were significantly lower than the derived acute and chronic effect concentrations for white sturgeon. Exposure risk quotients were calculated using the effect concentrations and estimated environmental exposure. The resulting values were considerably below the level of concern for direct effects from either acute or chronic exposure to an endangered species. PMID- 26351256 TI - Medical negligence and substandard drugs caused deaths in Indian sterilisation programme, report finds. PMID- 26351257 TI - Hierarchical Micro-Nano Surface Topography Promotes Long-Term Maintenance of Undifferentiated Mouse Embryonic Stem Cells. AB - Understanding of stem cell-surface interactions and, in particular, long-term maintenance of stem cell pluripotency on well-defined synthetic surfaces is crucial for fundamental research and biomedical applications of stem cells. Here, we show that synthetic surfaces possessing hierarchical micro-nano roughness (MN surfaces) promote long-term self-renewal (>3 weeks) of mouse embryonic stem cells (mESCs) as monitored by the expression levels of the pluripotency markers octamer binding transcription factor 4 (Oct4), Nanog, and alkaline phosphatase. On the contrary, culturing of mESCs on either smooth (S-) or nanorough polymer surfaces (N-surfaces) leads to their fast differentiation. Moreover, we show that regular passaging of mESCs on the hierarchical MN-polymer surface leads to an increased homogeneity and percentage of Oct4-positive stem cell colonies as compared to mESCs grown on fibroblast feeder cells. Immunostaining revealed the absence of focal adhesion markers on all polymer substrates studied. However, only the MN surfaces elicited the formation of actin-positive cell protrusions, indicating an alternative anchorage mechanism involved in the maintenance of mESC stemness. PMID- 26351258 TI - Telomeres are partly shielded from ultraviolet-induced damage and proficient for nucleotide excision repair of photoproducts. AB - Ultraviolet light induces cyclobutane pyrimidine dimers (CPD) and pyrimidine(6 4)pyrimidone photoproducts, which interfere with DNA replication and transcription. Nucleotide excision repair (NER) removes these photoproducts, but whether NER functions at telomeres is unresolved. Here we use immunospot blotting to examine the efficiency of photoproduct formation and removal at telomeres purified from UVC irradiated cells at various recovery times. Telomeres exhibit approximately twofold fewer photoproducts compared with the bulk genome in cells, and telomere-binding protein TRF1 significantly reduces photoproduct formation in telomeric fragments in vitro. CPD removal from telomeres occurs 1.5-fold faster than the bulk genome, and is completed by 48 h. 6-4PP removal is rapidly completed by 6 h in both telomeres and the overall genome. A requirement for XPA protein indicates the mechanism of telomeric photoproduct removal is NER. These data provide new evidence that telomeres are partially protected from ultraviolet irradiation and that NER preserves telomere integrity. PMID- 26351259 TI - The value of diagnostic ultrasonography in the assessment of a glomus tumor of the subcutaneous layer of the forearm mimicking a hemangioma: a case report. AB - INTRODUCTION: A glomus tumor is a rare, benign tumor with atypical clinical symptoms. Because of its small size, it is difficult to diagnose and treat early; therefore, it leads to poor quality of life. Glomus tumors are known to commonly affect the hand and rarely manifest in other areas. Because they simulate neuromas, hemangiomas, and neurofibromatosis, the differential diagnosis is difficult. We performed marginal resection of a solitary forearm mass previously suspected to be a hemangioma or glomus tumor on the basis of ultrasound findings and histologically diagnosed to be a glomus tumor afterward. We report this case to demonstrate the good prognosis of the procedure we used, and we review the relevant literature. CASE PRESENTATION: A 68-year-old Asian man without a particular medical history visited our hospital with a mass with focal tenderness in his left distal forearm that had developed 8 years earlier. The tumor was observed with suspicion of being a hemangioma or glomus tumor based on the location, clinical symptoms, and ultrasound findings taken into consideration together. The biopsy results led us to conclude that the lesion was a glomus tumor. CONCLUSIONS: A glomus tumor located in the forearm is very rare. It is often clinically overlooked and is likely to be misdiagnosed as another disease. The patient's quality of life deteriorates, and, though the disease is rare, it has serious sequelae. Therefore, a quick diagnosis and appropriate treatment must be conducted early. If a mass occurs with serious pain in subcutaneous soft tissue of not the hands but the limbs, it is important to conduct examinations with suspicion of a glomus tumor. Ultrasonography performed quickly may be useful for making the differential diagnosis. PMID- 26351260 TI - Incidence and causes of dental trauma in children living in the county of Varmland, Sweden. AB - AIM: The aims of this study were to determine the incidence of injuries to permanent incisors in 2011-2013 in children aged 8-10 years living in the county of Varmland, Sweden, and to compare it with the incidence rates in 1989/1990 in the county of Vastmanland, as well as to determine the cause of dental trauma in relation to time and place. METHOD: The study analysed the patient records from dental visits (2011-2013) of trauma to the permanent incisors in children aged 8 10 years. The incidence rates were the incidence per 1000 children at risk. Standardized incidence rates were calculated for the comparison between different years. Information about month, location where the trauma occurred as well as cause of trauma was recorded. RESULTS: A total of 2.2% of 21 721 children aged 8 10 years had experienced at least one trauma. The incidence rate in Varmland increased from 18.9 in 2011 to 21.3 in 2012 to 28.5 in 2013. The standardized incidence rate in Varmland in 2011 and 2012 was not significantly different than in Vastmanland in 1989/1990 (P > 0.05), but the standardized rates in 2013 were significantly higher than in 1989/90 (P < 0.001). Dental trauma occurred most often outdoors, followed by sports arenas/sports fields, and more often at school than at home. Falling and slipping was the most common cause of trauma, followed by accidents during leisure activities, playing and sports. CONCLUSION: The incidence rate for dental trauma has not decreased in the past 20 years, and there is an indication that parents and teachers should be more aware of the risks of dental trauma at leisure times and at school as well as during sports and exercise. PMID- 26351261 TI - Flutrack.org: Open-source and linked data for epidemiology. AB - Epidemiology has made advances, thanks to the availability of real-time surveillance data and by leveraging the geographic analysis of incidents. There are many health information systems that visualize the symptoms of influenza-like illness on a digital map, which is suitable for end-users, but it does not afford further processing and analysis. Existing systems have emphasized the collection, analysis, and visualization of surveillance data, but they have neglected a modular and interoperable design that integrates high-resolution geo-location with real-time data. As a remedy, we have built an open-source project and we have been operating an open service that detects flu-related symptoms and shares the data in real-time with anyone who wants to built upon this system. An analysis of a small number of precisely geo-located status updates (e.g. Twitter) correlates closely with the Google Flu Trends and the Centers for Disease Control and Prevention flu-positive reports. We suggest that public health information systems should embrace an open-source approach and offer linked data, in order to facilitate the development of an ecosystem of applications and services, and in order to be transparent to the general public interest. PMID- 26351262 TI - Transforming patient care by introducing an electronic medical records initiative in a developing country. AB - The incorporation of an electronic medical record into patient care is a priority in developed countries, but faces significant obstacles for adoption in developing countries. The goal of our study was to define and assess the efficiency of a personalized intervention on village physicians' use of electronic medical records in rural community health services of underprivileged areas. Six towns were selected with two bordering local health stations from each town. One was randomly given to the intervention group and the other to the control group. A structured on-site intervention was provided to village physicians in the intervention group, for 7 months. The results showed that in the intervention group, the percentage of households with complete records increased. The percentage of clinic medical records and complete child vaccination in the intervention group also increased from 2 to 14 percent (p = <0.05) and from 10 to 23 percent (p = 0.05), respectively. Our investigation demonstrated that on-site education, supervision, and technical support directly correlate with improved use of electronic medical record. Our results report the challenges in implementing such a system and the steps being taken to enhance likelihood of sustainability. PMID- 26351263 TI - Longitudinal impact of the Cyber Friendly Schools program on adolescents' cyberbullying behavior. AB - Cyberbullying is a major public health problem associated with serious mental, social, and academic consequences for young people. To date, few programs addressing cyberbullying have been developed and empirically tested. The Cyber Friendly Schools (CFS) group-randomized controlled trial measured the longitudinal impact of a whole-school online cyberbullying prevention and intervention program, developed in partnership with young people. Non-government secondary schools in Perth, Western Australia, (N = 35; 3,000+ students) were randomized to an intervention (n = 19) or usual practice control group (n = 16 schools). Students completed online questionnaires in 2010, 2011, and at 1-year follow-up in 2012, measuring their cyberbullying experiences during the previous school term. The intervention group received the program in Grades 8 and 9 (aged 13-14 years). Program effects were tested using two-part growth models. The program was associated with significantly greater declines in the odds of involvement in cyber-victimization and perpetration from pre- to the first post test, but no other differences were evident between the study conditions. However, teachers implemented only one third of the program content. More work is needed to build teacher capacity and self-efficacy to effectively implement cyberbullying programs. Whole-school cyberbullying interventions implemented in conjunction with other bullying prevention programs may reduce cyber victimization more than traditional school-based bullying prevention programs alone. Aggr. Behav. 42:166-180, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26351264 TI - NADH-Cytochrome b5 Reductase 3 Promotes Colonization and Metastasis Formation and Is a Prognostic Marker of Disease-Free and Overall Survival in Estrogen Receptor Negative Breast Cancer. AB - Metastasis is the main cause of cancer-related deaths and remains the most significant challenge to management of the disease. Metastases are established through a complex multistep process involving intracellular signaling pathways. To gain insight to proteins central to specific steps in metastasis formation, we used a metastasis cell line model that allows investigation of extravasation and colonization of circulating cancer cells to lungs in mice. Using stable isotopic labeling by amino acids in cell culture and subcellular fractionation, the nuclear, cytosol, and mitochondria proteomes were analyzed by LC-MS/MS, identifying a number of proteins that exhibited altered expression in isogenic metastatic versus nonmetastatic cancer cell lines, including NADH-cytochrome b5 reductase 3 (CYB5R3), l-lactate dehydrogenase A (LDHA), Niemann-pick c1 protein (NPC1), and nucleolar RNA helicase 2 (NRH2). The altered expression levels were validated at the protein and transcriptional levels, and analysis of breast cancer biopsies from two cohorts of patients demonstrated a significant correlation between high CYB5R3 expression and poor disease-free and overall survival in patients with estrogen receptor-negative tumors (DFS: p = .02, OS: p = .04). CYB5R3 gene knock-down using siRNA in metastasizing cells led to significantly decreased tumor burden in lungs when injected intravenously in immunodeficient mice. The cellular effects of CYB5R3 knock-down showed signaling alterations associated with extravasation, TGFbeta and HIFalpha pathways, and apoptosis. The decreased apoptosis of CYB5R3 knock-down metastatic cancer cell lines was confirmed in functional assays. Our study reveals a central role of CYB5R3 in extravasation/colonization of cancer cells and demonstrates the ability of our quantitative, comparative proteomic approach to identify key proteins of specific important biological processes that may also prove useful as potential biomarkers of clinical relevance. MS data are available via ProteomeXchange with identifier PXD001391. PMID- 26351265 TI - An urgent need to understand and address the safety and well-being of hospital "sitters". AB - BACKGROUND: Hospital sitters provide continuous observation of patients at risk of harming themselves or others. Little is known about sitters' occupational safety and well-being, including experiences with patient/visitor-perpetrated violence (type II). METHODS: Data from surveys, focus groups, individual interviews at six U.S. hospitals were used to characterize the prevalence of and circumstance surrounding type II violence against sitters, as well as broader issues related to sitter use. RESULTS: Sitter respondents had a high 12-month prevalence of physical assault, physical threat, and verbal abuse compared to other workers in the hospital setting. Sitters and other staff indicated the need for clarification of sitters' roles regarding patient care and sitter well-being (e.g., calling for assistance, taking lunch/restroom breaks), training of sitters in personal safety and de-escalation, methods to communicate patient/visitor behaviors, and unit-level support. CONCLUSIONS: The burden of type II violence against hospital sitters is concerning. Policies surrounding sitters' roles and violence prevention training are urgently needed. PMID- 26351266 TI - Born Fat: The Relations Between Weight Changeability Beliefs and Health Behaviors and Physical Health. AB - Although some popular press and nonscholarly sources have claimed that weight is largely unchangeable, the relationship between this belief and objective measures of health remains unclear. We tested the hypothesis that people who believe weight is unchangeable will have poorer objective and subjective health, and fewer exercise behaviors and poorer eating habits, than people who believe weight is changeable. Participants were 4,166 men and 4,655 women enrolled in the National Health and Nutrition Examination Survey in the 2007 to 2010 iterations. Believing that weight was uncontrollable was negatively related to exercise and healthful dietary practices and positively related to unhealthful eating. Lack of exercise and unhealthful eating were, in turn, associated with poor physical health. Age, but not gender, moderated the relationships between belief in weight changeability and exercise behaviors, healthful eating, and unhealthful eating. This study suggests that believing weight is unchangeable is associated with poor health behaviors and poorer physical health. PMID- 26351267 TI - The nature of magnetoelectric coupling in Pb(Zr,Ti)O3 -Pb(Fe,Ta)O3. AB - The coupling between magnetization and polarization in a room temperature multiferroic (Pb(Zr,Ti)O3 -Pb(Fe,Ta)O3 ) is explored by monitoring the changes in capacitance that occur when a magnetic field is applied in each of three orthogonal directions. Magnetocapacitance effects, consistent with P(2) M(2) coupling, are strongest when fields are applied in the plane of the single crystal sheet investigated. PMID- 26351268 TI - Client perceptions of group education in the management of type 2 diabetes mellitus in South Australia. AB - Type 2 diabetes mellitus (T2DM) is a progressive chronic disease that requires significant self-surveillance and adherence to the treatment protocols for successful management and future health. There is a growing body of evidence suggesting that diabetes education is beneficial for patient outcomes. However, there is some debate about how best to deliver diabetes education, whether individually or in groups. Although several studies have investigated the role of group education in improving the management of T2DM, few studies have examined this issue from the client's perspective. It is here that this study makes a contribution to understanding diabetes management. Drawing on systematic observation of group education sessions provided by diabetic resource nurses and in-depth interviews with clients, this paper describes the experiences, perspectives and significance of these sessions to clients. Our results suggest that group education sessions were seen as valuable to the clients for: the opportunity they provided to meet others living with diabetes; to improve motivation for managing the disease; and to enhance knowledge of diabetes, its management and long-term implications. In short, this study demonstrates that the clients value group education sessions for the social contact, increasing knowledge about the disease for self-management and support they provide; factors recognised as important to maintaining health. In addition, group education sessions appear to be a cost-effective method for diabetes self-management that funders need to consider. PMID- 26351269 TI - Reply: Skin biopsies in the differential diagnosis of parkinsonism: are we ready for simplified protocols? PMID- 26351270 TI - Skin biopsies in the differential diagnosis of parkinsonism: are we ready for simplified protocols? PMID- 26351272 TI - Pressure-induced phase transition in hydrothermally grown ZnO nanoflowers investigated by Raman and photoluminescence spectroscopy. AB - This paper reports the pressure-dependent photoluminescence and Raman spectral investigation of hydrothermally synthesized ZnO nanoflowers at room temperature. Intrinsic near-band-edge UV emission from ZnO nanoflowers is monotonously blue shifted under pressures up to 13.8 GPa with a pressure coefficient of 26 meV GPa( 1), and this pressure value is nearly 5 GPa above the transition pressure from the wurtzite to the rock salt phase for bulk ZnO. The Raman band corresponds to the wurtzite phase, the [Formula: see text] and [Formula: see text] modes were observed up to about 11 GPa from the spectra. The apparent discrepancy in the transition pressures as determined from photoluminescence and Raman studies suggests that it is a consequence of the gradual phase transition, in which the smallest nanoparticles are expected to remain in the wurtzite phase up to 13-15 GPa. PMID- 26351271 TI - Improved large-scale prediction of growth inhibition patterns using the NCI60 cancer cell line panel. AB - MOTIVATION: Recent large-scale omics initiatives have catalogued the somatic alterations of cancer cell line panels along with their pharmacological response to hundreds of compounds. In this study, we have explored these data to advance computational approaches that enable more effective and targeted use of current and future anticancer therapeutics. RESULTS: We modelled the 50% growth inhibition bioassay end-point (GI50) of 17,142 compounds screened against 59 cancer cell lines from the NCI60 panel (941,831 data-points, matrix 93.08% complete) by integrating the chemical and biological (cell line) information. We determine that the protein, gene transcript and miRNA abundance provide the highest predictive signal when modelling the GI50 endpoint, which significantly outperformed the DNA copy-number variation or exome sequencing data (Tukey's Honestly Significant Difference, P <0.05). We demonstrate that, within the limits of the data, our approach exhibits the ability to both interpolate and extrapolate compound bioactivities to new cell lines and tissues and, although to a lesser extent, to dissimilar compounds. Moreover, our approach outperforms previous models generated on the GDSC dataset. Finally, we determine that in the cases investigated in more detail, the predicted drug-pathway associations and growth inhibition patterns are mostly consistent with the experimental data, which also suggests the possibility of identifying genomic markers of drug sensitivity for novel compounds on novel cell lines. CONTACT: terez@pasteur.fr; ab454@ac.cam.uk SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26351273 TI - Growing Fixed With Age: Lay Theories of Malleability Are Target Age-Specific. AB - Beliefs about whether people can change ("lay theories" of malleability) are known to have wide-ranging effects on social motivation, cognition, and judgment. Yet rather than holding an overarching belief that people can or cannot change, perceivers may hold independent beliefs about whether different people are malleable-that is, lay theories may be target-specific. Seven studies demonstrate that lay theories are target-specific with respect to age: Perceivers hold distinct, uncorrelated lay theories of people at different ages, and younger targets are considered to be more malleable than older targets. Both forms of target-specificity are consequential, as target age-specific lay theories predict policy support for learning-based senior services and the rehabilitation of old and young drug users. The implications of target age-specific lay theories for a number of psychological processes, the social psychology of aging, and theoretical frameworks of malleability beliefs are discussed. PMID- 26351274 TI - Cultural Differences in Support Provision: The Importance of Relationship Quality. AB - Emotional expression is highly valued in individualistic cultures, whereas emotional restraint is prioritized in collectivistic cultures. We hypothesized that high-quality relationships in these cultures would exhibit the forms of support provision congruent with their respective expectations. Study 1 examined support transactions among friends in response to a laboratory stressor and found that objectively judged relationship quality (RQ) more strongly positively predicted emotion-focused support provision behaviors by European Americans than by Asian Americans. Study 2, a questionnaire study, found that self-reported RQ predicted emotion-focused support provision more strongly among European Americans than among Japanese. Study 3 investigated more indirect forms of support and found that RQ more strongly predicted worrying about and monitoring close others enduring stressors and spending time with them without talking about the stressor among Asian Americans compared with European Americans. These findings suggest that RQ is expressed in terms of support provision in culturally normative ways. PMID- 26351275 TI - Predicting pulmonary embolus in primary care. PMID- 26351276 TI - Bioluminescent imaging reveals novel patterns of colonization and invasion in systemic Escherichia coli K1 experimental infection in the neonatal rat. AB - Key features of Escherichia coli K1-mediated neonatal sepsis and meningitis, such as a strong age dependency and development along the gut-mesentery-blood-brain course of infection, can be replicated in the newborn rat. We examined temporal and spatial aspects of E. coli K1 infection following initiation of gastrointestinal colonization in 2-day-old (P2) rats after oral administration of E. coli K1 strain A192PP and a virulent bioluminescent derivative, E. coli A192PP lux2. A combination of bacterial enumeration in the major organs, two-dimensional bioluminescence imaging, and three-dimensional diffuse light imaging tomography with integrated micro-computed tomography indicated multiple sites of colonization within the alimentary canal; these included the tongue, esophagus, and stomach in addition to the small intestine and colon. After invasion of the blood compartment, the bacteria entered the central nervous system, with restricted colonization of the brain, and also invaded the major organs, in line with increases in the severity of symptoms of infection. Both keratinized and nonkeratinized surfaces of esophagi were colonized to a considerably greater extent in susceptible P2 neonates than in corresponding tissues from infection resistant 9-day-old rat pups; the bacteria appeared to damage and penetrate the nonkeratinized esophageal epithelium of infection-susceptible P2 animals, suggesting the esophagus represents a portal of entry for E. coli K1 into the systemic circulation. Thus, multimodality imaging of experimental systemic infections in real time indicates complex dynamic patterns of colonization and dissemination that provide new insights into the E. coli K1 infection of the neonatal rat. PMID- 26351277 TI - STAT1 signaling within macrophages is required for antifungal activity against Cryptococcus neoformans. AB - Cryptococcus neoformans, the predominant etiological agent of cryptococcosis, is an opportunistic fungal pathogen that primarily affects AIDS patients and patients undergoing immunosuppressive therapy. In immunocompromised individuals, C. neoformans can lead to life-threatening meningoencephalitis. Studies using a virulent strain of C. neoformans engineered to produce gamma interferon (IFN gamma), denoted H99gamma, demonstrated that protection against pulmonary C. neoformans infection is associated with the generation of a T helper 1 (Th1)-type immune response and signal transducer and activator of transcription 1 (STAT1) mediated classical (M1) macrophage activation. However, the critical mechanism by which M1 macrophages mediate their anti-C. neoformans activity remains unknown. The current studies demonstrate that infection with C. neoformans strain H99gamma in mice with macrophage-specific STAT1 ablation resulted in severely increased inflammation of the pulmonary tissue, a dysregulated Th1/Th2-type immune response, increased fungal burden, deficient M1 macrophage activation, and loss of protection. STAT1-deficient macrophages produced significantly less nitric oxide (NO) than STAT1-sufficient macrophages, correlating with an inability to control intracellular cryptococcal proliferation, even in the presence of reactive oxygen species (ROS). Furthermore, macrophages from inducible nitric oxide synthase knockout mice, which had intact ROS production, were deficient in anticryptococcal activity. These data indicate that STAT1 activation within macrophages is required for M1 macrophage activation and anti-C. neoformans activity via the production of NO. PMID- 26351278 TI - Nonredundant Roles of Interleukin-17A (IL-17A) and IL-22 in Murine Host Defense against Cutaneous and Hematogenous Infection Due to Methicillin-Resistant Staphylococcus aureus. AB - Staphylococcus aureus is the leading cause of skin and skin structure infections (SSSI) in humans. Moreover, the high frequency of recurring SSSI due to S. aureus, particularly methicillin-resistant S. aureus (MRSA) strains, suggests that infection induces suboptimal anamnestic defenses. The present study addresses the hypothesis that interleukin-17A (IL-17A) and IL-22 play distinct roles in immunity to cutaneous and invasive MRSA infection in a mouse model of SSSI. Mice were treated with specific neutralizing antibodies against IL-17A and/or IL-22 and infected with MRSA, after which the severity of infection and host immune response were determined. Neutralization of either IL-17A or IL-22 reduced T cell and neutrophil infiltration and host defense peptide elaboration in lesions. These events corresponded with increased abscess severity, MRSA viability, and CFU density in skin. Interestingly, combined inhibition of IL-17A and IL-22 did not worsen abscesses but did increase gamma interferon (IFN-gamma) expression at these sites. The inhibition of IL-22 led to a reduction in IL-17A expression, but not vice versa. These results suggest that the expression of IL 17A is at least partially dependent on IL-22 in this model. Inhibition of IL-17A but not IL-22 led to hematogenous dissemination to kidneys, which correlated with decreased T cell infiltration in renal tissue. Collectively, these findings indicate that IL-17A and IL-22 have complementary but nonredundant roles in host defense against cutaneous versus hematogenous infection. These insights may support targeted immune enhancement or other novel approaches to address the challenge of MRSA infection. PMID- 26351279 TI - TIR Domain-Containing Adapter-Inducing Beta Interferon (TRIF) Mediates Immunological Memory against Bacterial Pathogens. AB - Induction of adaptive immunity leads to the establishment of immunological memory; however, how innate immunity regulates memory T cell function remains obscure. Here we show a previously undefined mechanism in which innate and adaptive immunity are linked by TIR domain-containing adapter-inducing beta interferon (TRIF) during establishment and reactivation of memory T cells against Gram-negative enteropathogens. Absence of TRIF in macrophages (Mphis) but not dendritic cells led to a predominant generation of CD4(+) central memory T cells that express IL-17 during enteric bacterial infection in mice. TRIF-dependent type I interferon (IFN) signaling in T cells was essential to Th1 lineage differentiation and reactivation of memory T cells. TRIF activated memory T cells to facilitate local neutrophil influx and enhance bacterial elimination. These results highlight the importance of TRIF as a mediator of the innate and adaptive immune interactions in achieving the protective properties of memory immunity against Gram-negative bacteria and suggest TRIF as a potential therapeutic target. PMID- 26351280 TI - LL-37 immunomodulatory activity during Mycobacterium tuberculosis infection in macrophages. AB - Tuberculosis is one of the most important infectious diseases worldwide. The susceptibility to this disease depends to a great extent on the innate immune response against mycobacteria. Host defense peptides (HDP) are one of the first barriers to counteract infection. Cathelicidin (LL-37) is an HDP that has many immunomodulatory effects besides its weak antimicrobial activity. Despite advances in the study of the innate immune response in tuberculosis, the immunological role of LL-37 during M. tuberculosis infection has not been clarified. Monocyte-derived macrophages were infected with M. tuberculosis strain H37Rv and then treated with 1, 5, or 15 MUg/ml of exogenous LL-37 for 4, 8, and 24 h. Exogenous LL-37 decreased tumor necrosis factor alpha (TNF-alpha) and interleukin-17 (IL-17) while inducing anti-inflammatory IL-10 and transforming growth factor beta (TGF-beta) production. Interestingly, the decreased production of anti-inflammatory cytokines did not reduce antimycobacterial activity. These results are consistent with the concept that LL-37 can modulate the expression of cytokines during mycobacterial infection and this activity was independent of the P2X7 receptor. Thus, LL-37 modulates the response of macrophages during infection, controlling the expression of proinflammatory and anti-inflammatory cytokines. PMID- 26351281 TI - Glycyrrhizic acid-mediated subdual of myeloid-derived suppressor cells induces antileishmanial immune responses in a susceptible host. AB - CD11b(+) Gr1(+) myeloid-derived suppressor cells (MDSCs), a heterogeneous population of precursor cells, modulate protective immunity against visceral leishmaniasis by suppressing T cell functions. We observed that CD11b(+) Gr1(+) MDSCs, which initially expanded in soluble leishmanial antigen (SLA)-immunized mice and later diminished, suppressed proliferation of T cells isolated from SLA immunized mice, but to a lesser extent than the case in naive mice. This lesser suppression of MDSCs accompanied the expression of F4/80 and the production of Cox-2, arginase I, nitric oxide, and PGE2. However, with SLA immunization, there was no difference in the expression of interleukin-2 (IL-2) or gamma interferon (IFN-gamma) by T cells, in contrast to the case in nonimmunized mice, in which there is an influence. Glycyrrhizic acid (a triterpenoid compound)-mediated inhibition of Cox-2 in myeloid-derived suppressor cells influenced the capacity of T cells to proliferate and the expression of IL-2 and IFN-gamma in Leishmania donovani-infected BALB/c mice. Further characterization confirmed that administration of glycyrrhizic acid to L. donovani-infected BALB/c mice results in an impairment of the generation of MDSCs and a reciprocal organ-specific proliferation of IFN-gamma- and IL-10-expressing CD4(+) and CD8(+) T cells. Comprehensive knowledge on the Cox-2-mediated regulation of myeloid-derived suppressor cells might be involved in unlocking a new avenue for therapeutic interventions during visceral leishmaniasis. PMID- 26351282 TI - The Makes Caterpillars Floppy (MCF)-Like Domain of Vibrio vulnificus Induces Mitochondrion-Mediated Apoptosis. AB - The multifunctional-autoprocessing repeats-in-toxin (MARTXVv) toxin of Vibrio vulnificus plays a significant role in the pathogenesis of this bacterium through delivery of up to five effector domains to the host cells. Previous studies have established that the MARTXVv toxin is linked to V. vulnificus dependent induction of apoptosis, but the region of the large multifunction protein essential for this activity was not previously identified. Recently, we showed that the Makes Caterpillar Floppy-like MARTX effector domain (MCFVv) is an autoproteolytic cysteine protease that induces rounding of various cell types. In this study, we demonstrate that cell rounding induced by MCFVv is coupled to reduced metabolic rate and inhibition of cellular proliferation. Moreover, delivery of MCFVv into host cells either as a fusion to the N-terminal fragment of anthrax toxin lethal factor or when naturally delivered as a V. vulnificus MARTX toxin led to loss of mitochondrial membrane potential, release of cytochrome c, activation of Bax and Bak, and processing of caspases and poly-(ADP-ribose) polymerase (PARP-gamma). These studies specifically link the MCFVv effector domain to induction of the intrinsic apoptosis pathway by V. vulnificus. PMID- 26351283 TI - Beyond the Crystal Structure: Insight into the Function and Vaccine Potential of TbpA Expressed by Neisseria gonorrhoeae. AB - Neisseria gonorrhoeae, the causative agent of the sexually transmitted infection gonorrhea, is not preventable by vaccination and is rapidly developing resistance to antibiotics. However, the transferrin (Tf) receptor system, composed of TbpA and TbpB, is an ideal target for novel therapeutics and vaccine development. Using a three-dimensional structure of gonococcal TbpA, we investigated two hypotheses, i.e., that loop-derived antibodies can interrupt ligand-receptor interactions in the native bacterium and that the loop 3 helix is a critical functional domain. Preliminary loop-derived antibodies, as well as optimized second-generation antibodies, demonstrated similar modest ligand-blocking effects on the gonococcal surface but different effects in Escherichia coli. Mutagenesis of loop 3 helix residues was employed, generating 11 mutants. We separately analyzed the mutants' abilities to (i) bind Tf and (ii) internalize Tf-bound iron in the absence of the coreceptor TbpB. Single residue mutations resulted in up to 60% reductions in ligand binding and up to 85% reductions in iron utilization. All strains were capable of growing on Tf as the sole iron source. Interestingly, in the presence of TbpB, only a 30% reduction in Tf-iron utilization was observed, indicating that the coreceptor can compensate for TbpA impairment. Complete deletion of the loop 3 helix of TbpA eliminated the abilities to bind Tf, internalize iron, and grow with Tf as the sole iron source. Our studies demonstrate that while the loop 3 helix is a key functional domain, its function does not exclusively rely on any single residue. PMID- 26351284 TI - The Candida albicans ATO Gene Family Promotes Neutralization of the Macrophage Phagolysosome. AB - Candida albicans is an opportunistic human fungal pathogen that causes a variety of diseases, ranging from superficial mucosal to life-threatening systemic infections, the latter particularly in patients with defects in innate immune function. C. albicans cells phagocytosed by macrophages undergo a dramatic change in their metabolism in which amino acids are a key nutrient. We have shown that amino acid catabolism allows the cell to neutralize the phagolysosome and initiate hyphal growth. We show here that members of the 10-gene ATO family, which are induced by phagocytosis or the presence of amino acids in an Stp2 dependent manner and encode putative acetate or ammonia transporters, are important effectors of this pH change in vitro and in macrophages. When grown with amino acids as the sole carbon source, the deletion of ATO5 or the expression of a dominant-negative ATO1(G53D) allele results in a delay in alkalinization, a defect in hyphal formation, and a reduction in the amount of ammonia released from the cell. These strains also form fewer hyphae after phagocytosis, have a reduced ability to escape macrophages, and reside in more acidic phagolysosomal compartments than wild-type cells. Furthermore, overexpression of many of the 10 ATO genes accelerates ammonia release, and an ato5Delta ATO1(G53D) double mutant strain has additive alkalinization and ammonia release defects. Taken together, these results indicate that the Ato protein family is a key mediator of the metabolic changes that allow C. albicans to overcome the macrophage innate immunity barrier. PMID- 26351285 TI - Refined live attenuated Salmonella enterica serovar Typhimurium and Enteritidis vaccines mediate homologous and heterologous serogroup protection in mice. AB - Invasive nontyphoidal Salmonella (NTS) infections constitute a major health problem among infants and toddlers in sub-Saharan Africa; these infections also occur in infants and the elderly in developed countries. We genetically engineered a Salmonella enterica serovar Typhimurium strain of multilocus sequence type 313, the predominant genotype circulating in sub-Saharan Africa. We evaluated the capacities of S. Typhimurium and Salmonella enterica serovar Enteritidis DeltaguaBA DeltaclpX live oral vaccines to protect mice against a highly lethal challenge dose of the homologous serovar and determined protection against other group B and D serovars circulating in sub-Saharan Africa. The vaccines S. Typhimurium CVD 1931 and S. Enteritidis CVD 1944 were immunogenic and protected BALB/c mice against 10,000 50% lethal doses (LD50) of S. Typhimurium or S. Enteritidis, respectively. S. Typhimurium CVD 1931 protected mice against the group B serovar Salmonella enterica serovar Stanleyville (91% vaccine efficacy), and S. Enteritidis CVD 1944 protected mice against the group D serovar Salmonella enterica serovar Dublin (85% vaccine efficacy). High rates of survival were observed when mice were infected 12 weeks postimmunization, indicating that the vaccines elicited long-lived protective immunity. Whereas CVD 1931 did not protect against S. Enteritidis R11, CVD 1944 did mediate protection against S. Typhimurium D65 (81% efficacy). These findings suggest that a bivalent (S. Typhimurium and S. Enteritidis) vaccine would provide broad protection against the majority of invasive NTS infections in sub-Saharan Africa. PMID- 26351286 TI - The fibronectin-binding protein EfbA contributes to pathogenesis and protects against infective endocarditis caused by Enterococcus faecalis. AB - EfbA is a PavA-like fibronectin adhesin of Enterococcus faecalis previously shown to be important in experimental urinary tract infection. Here, we expressed and purified the E. faecalis OG1RF EfbA and confirmed that this protein binds with high affinity to immobilized fibronectin, collagen I, and collagen V. We constructed an efbA deletion mutant and demonstrated that its virulence was significantly attenuated (P < 0.0006) versus the wild type in a mixed inoculum rat endocarditis model. Furthermore, efbA deletion resulted in diminished ability to bind fibronectin (P < 0.0001) and reduced biofilm (P < 0.001). Reintroduction of efbA into the original chromosomal location restored virulence, adherence to fibronectin, and biofilm formation to wild-type levels. Finally, vaccination of rats with purified recombinant EfbA protein protected against OG1RF endocarditis (P = 0.008 versus control). Taken together, our results demonstrate that EfbA is an important factor involved in E. faecalis endocarditis and that rEfbA immunization is effective in preventing such infection, likely by interfering with bacterial adherence. PMID- 26351288 TI - The Ankle-Brachial Index is Associated With Cardiovascular Complications After Noncardiac Surgery. PMID- 26351287 TI - Role of host cell-derived amino acids in nutrition of intracellular Salmonella enterica. AB - The facultative intracellular pathogen Salmonella enterica resides in a specific membrane-bound compartment termed the Salmonella-containing vacuole (SCV). Despite being segregated from access to metabolites in the host cell cytosol, Salmonella is able to efficiently proliferate within the SCV. We set out to unravel the nutritional supply of Salmonella in the SCV with focus on amino acids. We studied the availability of amino acids by the generation of auxotrophic strains for alanine, asparagine, aspartate, glutamine, and proline in a macrophage cell line (RAW264.7) and an epithelial cell line (HeLa) and examined access to extracellular nutrients for nutrition. Auxotrophies for alanine, asparagine, or proline attenuated intracellular replication in HeLa cells, while aspartate, asparagine, or proline auxotrophies attenuated intracellular replication in RAW264.7 macrophages. The different patterns of intracellular attenuation of alanine- or aspartate-auxotrophic strains support distinct nutritional conditions in HeLa cells and RAW264.7 macrophages. Supplementation of medium with individual amino acids restored the intracellular replication of mutant strains auxotrophic for asparagine, proline, or glutamine. Similarly, a mutant strain deficient in succinate dehydrogenase was complemented by the extracellular addition of succinate. Complementation of the intracellular replication of auxotrophic Salmonella by external amino acids was possible if bacteria were proficient in the induction of Salmonella-induced filaments (SIFs) but failed in a SIF-deficient background. We propose that the ability of intracellular Salmonella to redirect host cell vesicular transport provides access of amino acids to auxotrophic strains and, more generally, is essential to continuously supply bacteria within the SCV with nutrients. PMID- 26351289 TI - Women Undergoing Coronary Angiography for Myocardial Infarction or Who Present With Multivessel Disease Have a Poorer Prognosis Than Men. AB - BACKGROUND: Coronary artery disease affects both men and women. In this study, we examine sex-specific differences in occurrence of major adverse cardiovascular events (MACEs) after coronary angiography. METHODS: We analyzed data from the coronary angiography cohort Utrecht Coronary Biobank (n = 1283 men, 480 women). Using Kaplan-Meier and multivariable Cox-regression, we tested for sex differences in MACE occurrence. Additionally, we compared mortality with an age- and sex-matched control group from the general Dutch population. RESULTS: During a median follow-up of 2.1 years (interquartile range 1.6-2.8), MACEs occurred in 265 men and 103 women (20.7% vs 21.3%, P = .744). Women with myocardial infarction (MI) had significantly more MACE during follow-up than men (hazard ratio [HR] 1.66 for female sex, 95% confidence interval [CI] 1.10-2.50, P = .015), which was also the case for women who had multivessel disease (HR 1.41, 95% CI 1.03-1.94, P = .031). During follow-up, mortality in women presenting with MI was higher than mortality of women in the general population; men with MI did not show this disadvantage. CONCLUSION: MACEs occurred more often in women than in men who presented with MI or who had angiographic multivessel disease upon coronary angiography. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02304744. URL: https://clinicaltrials.gov/ct2/show/NCT02304744. PMID- 26351290 TI - Global deletion of BCATm increases expression of skeletal muscle genes associated with protein turnover. AB - Consumption of a protein-containing meal by a fasted animal promotes protein accretion in skeletal muscle, in part through leucine stimulation of protein synthesis and indirectly through repression of protein degradation mediated by its metabolite, alpha-ketoisocaproate. Mice lacking the mitochondrial branched chain aminotransferase (BCATm/Bcat2), which interconverts leucine and alpha ketoisocaproate, exhibit elevated protein turnover. Here, the transcriptomes of gastrocnemius muscle from BCATm knockout (KO) and wild-type mice were compared by next-generation RNA sequencing (RNA-Seq) to identify potential adaptations associated with their persistently altered nutrient signaling. Statistically significant changes in the abundance of 1,486/~39,010 genes were identified. Bioinformatics analysis of the RNA-Seq data indicated that pathways involved in protein synthesis [eukaryotic initiation factor (eIF)-2, mammalian target of rapamycin, eIF4, and p70S6K pathways including 40S and 60S ribosomal proteins], protein breakdown (e.g., ubiquitin mediated), and muscle degeneration (apoptosis, atrophy, myopathy, and cell death) were upregulated. Also in agreement with our previous observations, the abundance of mRNAs associated with reduced body size, glycemia, plasma insulin, and lipid signaling pathways was altered in BCATm KO mice. Consistently, genes encoding anaerobic and/or oxidative metabolism of carbohydrate, fatty acids, and branched chain amino acids were modestly but systematically reduced. Although there was no indication that muscle fiber type was different between KO and wild-type mice, a difference in the abundance of mRNAs associated with a muscular dystrophy phenotype was observed, consistent with the published exercise intolerance of these mice. The results suggest transcriptional adaptations occur in BCATm KO mice that along with altered nutrient signaling may contribute to their previously reported protein turnover, metabolic and exercise phenotypes. PMID- 26351291 TI - An 11-year retrospective review of venlafaxine ingestion in children from the California Poison Control System. AB - Venlafaxine is commonly used in the United States for approved and non-Food and Drug Administration-approved indications in adults. It is used off-label to treat children for psychiatric diagnoses. The aim of the study was to describe venlafaxine toxicities in children and to identify the venlafaxine dose per weight that correlates with toxicities. An 11-year retrospective study of venlafaxine ingestion in children was performed using the California Poison Control System (CPCS) database. Data was extracted from phone calls received by CPCS clinicians and follow-up phone calls made to assess the patient's progress in a health-care setting. Inclusion criteria were venlafaxine ingestion cases reported to CPCS between January 2001 and December 2011, children aged 20 years and under, venlafaxine as the only ingested substance, managed in a health-care facility, and followed to a known outcome. Two hundred sixty-two cases met the study criteria. Common presentations included gastrointestinal (14.9%), altered mental status (13.7%), and tachycardia (13.4%). The majority of the cases resulted in no effect (51.5%) or minor effect (19.9%). The average estimated dose per weight was 18.3 mg/kg in all patients and 64.5 mg/kg in those experiencing moderate-to-severe adverse effects. Seizures occurred in only 4 of the 262 cases at doses ranging from 1500 to 7500 mg. Although the estimated dose per weight exceeded 10 mg/kg for the majority of the cases, only 12 cases resulted in moderate or severe outcomes. The majority of venlafaxine ingestion cases in children resulted in either no clinical effects or minor clinical effects. PMID- 26351292 TI - Couple's Narratives of Communion and Isolation Following Abnormal Prenatal Microarray Testing Results. AB - In 2% to 3% of cases, prenatal microarray testing detects deletions and duplications in a fetus' genome that are undetected by conventional cytogenetics. Many of these changes are associated with variable or uncertain symptomatology. Little is known about how couples experience uncertain results. This study analyzed 24 interviews with members of 12 heterosexual U.S. couples who received pathogenic or uncertain microarray prenatal testing results. Researchers used narrative analysis to examine couples' understanding and incorporation of findings into decision making regarding pregnancy termination. Couples felt unprepared for these findings and frustrated because scant information was available to aid interpretation. Women sought information and made decisions, and men marginalized their distress to support their wives. A shift in voice from first to second person indicated attempts to normalize emotional responses by making the process "common" to all couples. Families pursuing highly sensitive prenatal testing may need expert guidance to support decision making. PMID- 26351293 TI - The Impact of a Cultural Immersion Study Abroad Experience in Traditional Chinese Medicine. AB - Study abroad programs have increased dramatically. Most programs are short-term and include a cultural immersion as well as classroom and/or service learning. In this article, the authors discuss a study abroad program to China that included cultural immersion and classroom learning specific to traditional Chinese medicine. Participants kept journals with specific writing assignments and reflections about their experiences during the trip. At the conclusion of the trip, a qualitative survey was administered to the participants. Outcomes included the benefits of cultural immersion and a greater appreciation of cultural diversity, complementary and alternative medicine and holistic health care. Participants were able to describe transformational experiences of living in and learning from the Chinese culture and peoples. They intended to incorporate their experiences and enhanced understanding of traditional Chinese medicine and complementary and alternative therapies to provide culturally competent holistic health care in their nursing practice. PMID- 26351294 TI - Nurses as Instruments of Healing: Self-Care Practices of Nurses in a Rural Hospital Setting. AB - OBJECTIVE: To better understand current self-care practices and health-promoting behaviors of nursing staff in a rural hospital and determine if there is a need for further development of a holistic self-care program for nursing staff in the hospital. METHOD: In this cross-sectional, descriptive study, a structured questionnaire was used to collect data on current self-care practices and health needs and interests of hospital registered nurses, licensed practical nurses, and certified nursing assistants from inpatient, outpatient, and emergency departments. A convenience sample of 45 was employed. RESULTS: Most prevalent self-care practices included humor/laughter/play, music, spirituality/prayer, healthy sleep habits, reading, healthy nutrition, and walking. At least 75.6% answered to be extremely or likely to use three of five fitness programs (95% confidence interval [CI: 63.05%, 88.15%]). All four nutrition education programs were rated extremely likely or likely by at least two thirds of respondents (66.7%; 95% CI [52.93%, 80.47%]). Other programs of interests included health education programs and job stress management programs. Majority would participate in self-care program at work if one was offered (73.3%; 95% CI [60.37%, 86.23%]). CONCLUSIONS: Majority of nursing staff recognize the importance of self-care. There is a strong preference toward fitness programs and nutrition education programs at work to other programs. PMID- 26351296 TI - Hybridization and the Origin of Contagious Asexuality in Daphnia pulex. AB - Hybridization plays a potentially important role in the origin of obligate parthenogenesis (OP) in many organisms. However, it remains controversial whether hybridization directly triggers the transition from sexual reproduction to obligate asexuality or a hybrid genetic background enables asexual species to persist. Furthermore, we know little about the specific genetic elements from the divergent, yet still hybridizing lineages responsible for this transition and how these elements are further spread to create other OP lineages. In this study, we address these questions in Daphnia pulex, where cyclically parthenogenetic (CP) and OP lineages coexist. Ancestry estimates and whole-genome association mapping using 32 OP isolates suggest that a complex hybridization history between the parental species D. pulex and D. pulicaria is responsible for the introgression of a set of 647 D. pulicaria single nucleotide polymorphism alleles that show perfect association with OP. Crossing experiments using males of OP lineages and females of CP lineages strongly support a polygenic basis for OP. Single-sperm analyses show that although normal meiotic recombination occurs in the production of haploid sperm by males of OP lineages, a significant proportion of such sperm are polyploid, suggesting that the spread of asexual elements through these males (i.e., contagious asexuality) is much less efficient than previously envisioned. Although the current Daphnia genome annotation does not provide mechanistic insight into the nature of the asexuality-associated alleles, these alleles should be considered as candidates for future investigations on the genetic underpinnings of OP. PMID- 26351297 TI - Outcome of patients with distinct molecular genotypes and cytogenetically normal AML after allogeneic transplantation. AB - To analyze the influence of distinct combinations of molecular aberrations on outcome after allogeneic hematopoietic stem cell transplantation (HSCT) for cytogenetically normal acute myeloid leukemia (CN-AML), a retrospective registry analysis was performed on 702 adults undergoing HSCT in first complete remission (CR). Patients were grouped according to presence or absence of NPM1 mutations (NPM1(mut)) and FLT3 internal tandem duplications (FLT3-ITD). Double-negative patients were evaluated for mutations of the CCAAT/enhancer binding protein alpha gene (CEBPalpha). The influence of genotypes on relapse, non-relapse mortality, leukemia-free survival (LFS) and overall survival (OS), and a prognostic classification combining NPM1/FLT3-ITD profile and classical risk factors were calculated. Two-year OS from HSCT was 81 +/- 5% in NPM1(mut)/FLT3(wt), 75 +/- 3% in NPM1(wt)/FLT3(wt), 66 +/- 3% in NPM1(mut)/FLT3-ITD, and 54 +/- 7% in NPM1(wt)/FLT3-ITD (P = .003). Analysis of CEBPalpha among patients with NPM1(wt)/FLT3(wt) revealed excellent results both in patients with CEBPalpha(mut) and with a triple negative genotype (2-year OS: 100%/77 +/- 3%). In a Cox-model of predefined variables, age, FLT3-ITD and >1 course of chemotherapy to reach CR were risk factors associated with inferior outcome, regardless of NPM1 mutational status, variations of transplant protocols, or development of graft-versus-host disease. In a prognostic risk classification, 2-year OS/LFS rates were 88 +/- 3%/79 +/- 4% without any, 77 +/- 2%/73 +/- 3% with one, and 53 +/- 4%/50 +/- 4 with >=2 risk factors (P = .003/.002). PMID- 26351299 TI - Dispositional Mindfulness as a Moderator of the Relationship Between Perceived Partner Infidelity and Women's Dating Violence Perpetration. AB - Mindfulness gained increased attention as it relates to aggressive behavior, including dating violence. However, no known studies examined how the combined influences of dispositional mindfulness and perceived partner infidelity, a well documented correlate of dating violence, relate to women's dating violence perpetration. Using a sample of college women ( N = 203), we examined the relationship between perceived partner infidelity and physical dating violence perpetration at varying levels of dispositional mindfulness, controlling for the influence of alcohol use. Results indicated perceived partner infidelity and dating violence perpetration were positively related for women with low and mean dispositional mindfulness, but not for women with high dispositional mindfulness. These results further support the applicability of mindfulness theory in the context of dating violence. Implications of the present findings provide preliminary support for mindfulness intervention in relationships characterized by infidelity concerns. PMID- 26351300 TI - Erratum. PMID- 26351298 TI - Platelet-derived Wnt antagonist Dickkopf-1 is implicated in ICAM-1/VCAM-1 mediated neutrophilic acute lung inflammation. AB - Neutrophil infiltration represents the early acute inflammatory response in acute lung injury. The recruitment of neutrophils from the peripheral blood across the endothelial-epithelial barrier into the alveolar airspace is highly regulated by the adhesion molecules on alveolar epithelial cells (AECs). Wnt/beta-catenin signaling is involved in the progression of inflammatory lung diseases including asthma, emphysema, and pulmonary fibrosis. However, the function of Wnt/beta catenin signaling in acute lung inflammation is unknown. Here, we identified platelet-derived Dickkopf-1 (Dkk1) as the major Wnt antagonist contributing to the suppression of Wnt/beta-catenin signaling in AECs during acute lung inflammation. Intratracheal administration of Wnt3a or an antibody capable of neutralizing Dkk1 inhibited neutrophil influx into the alveolar airspace of injured lungs. Activation of Wnt/beta-catenin signaling in AECs attenuated intercellular adhesion molecule 1 (ICAM-1)/vascular cell adhesion molecule 1 (VCAM-1)-mediated adhesion of both macrophages and neutrophils to AECs. Our results suggest a role for Wnt/beta-catenin signaling in modulating the inflammatory response, and a functional communication between platelets and AECs during acute lung inflammation. Targeting Wnt/beta-catenin signaling and the communication between platelets and AECs therefore represents potential therapeutic strategies to limit the damage of acute pulmonary inflammation. PMID- 26351301 TI - Exposure based therapy for problem gambling in a patient with Alzheimer's dementia. AB - OBJECTIVES: This case report discusses the response to exposure and response prevention therapy in a patient with problem gambling and comorbid early dementia. It further discusses neurobiology of exposure therapy and its application in patients with mild cognitive impairment. CONCLUSION: Studies show good response to the use of exposure therapy in patients with cognitive impairment and further studies are needed to study the neurobiological changes and response to the therapy in patients with cognitive impairment. PMID- 26351302 TI - Computed Tomography Evaluation of Density Following Stereotactic Body Radiation Therapy of Nonspine Bone Metastases. AB - INTRODUCTION: Stereotactic body radiation therapy allows for the precise delivery of high-dose radiation to disease sites and is becoming increasingly used to treat nonspine bone metastases. Previous studies have shown that remineralization of lytic bone metastases follows after conventional radiotherapy. The objective of this study was to investigate changes in bone density in nonspine bone metastases following stereotactic body radiation therapy. METHODS: A retrospective review was conducted for all patients treated with stereotactic body radiation therapy to nonspine bone metastases between May 2011 and April 2014. A minimum of 1 pretreatment and 1 posttreatment computed tomography scan was required. An independent musculoskeletal radiologist contoured the lesions on the most representative computed tomography slices. Density was measured in Hounsfield units and analyzed using pretreatment and posttreatment ratios. RESULTS: Forty sites were treated (55% lytic, 30% sclerotic, and 15% mixed). The median follow-up duration was 7 months. Lytic osseous metastases from renal cell carcinoma progressed during initial follow-up imaging and then returned to baseline. Of 9 lytic lesions not from renal cell carcinoma, 6 showed an immediate increase in density and 2 remained stable. Six of 7 sclerotic lesions from prostate cancer showed decreased density throughout all follow-ups. CONCLUSION: Stereotactic body radiation therapy is efficacious in the remineralization of lytic and demineralization of sclerotic nonspine bone metastases. PMID- 26351304 TI - HIV infection in pregnancy: maternal and perinatal outcomes in a tertiary care hospital in Calabar, Nigeria. AB - BACKGROUND: Human immunodeficiency virus (HIV) infection is likely to have untoward effects on pregnancy and its outcome. This study assessed the impact of maternal HIV infection on pregnancy outcomes in a tertiary centre in Calabar, Nigeria. METHODS: This retrospective study analysed delivery records of 258 HIV positive and 257 HIV-negative women for pregnancy and delivery complications. Maternal and fetal outcomes of HIV-positive pregnancies were compared with those of HIV-negative controls. RESULTS: Adverse pregnancy outcomes significantly associated with HIV status were: anaemia: 33 (8.1%) vs. 8 (3.1%) in controls; puerperal sepsis: 18 (7%) vs. 2 (0.8%); and low birth weight: 56 (21.7%) vs. 37 (14.4%). Caesarean delivery was higher among HIV-positive women than controls: 96 (37.2%) vs. 58 (22.6%). Preterm births were higher in those HIV cohorts who did not receive antiretroviral therapy (ART): 13 (16.9%) vs. 7 (3.9%). CONCLUSION: HIV-positive status increased adverse birth outcome of pregnancy. ART appeared to reduce the risk of preterm births in HIV-positive cohorts. PMID- 26351303 TI - Feasibility of Electroporation in Bone and in the Surrounding Clinically Relevant Structures: A Preclinical Investigation. AB - Skeletal metastases are a common cause of severe morbidity, reduction in quality of life and often early mortality. Consequently, improvements in therapies are necessary. Electroporation uses electric energy to alter cancer cell membrane permeability and enhance the local uptake of chemotherapeutics, thus leading to local tumor control. The aim of this study was to investigate the feasibility and safety of delivering electric field protocols causing electroporation of healthy bone and structures of clinical relevance using small and large animal models. Reversible electroporation was used in the rabbit sciatic nerve by applying 2 series of 8 pulses 100ms long at 1000 V/cm. Irreversible electroporation was used in rabbit distal femur condyles and in sheep vertebral body by applying 120 pulses 100ms long at 1750 V/cm. Any effect on surrounding sensitive structures was investigated. Reversible electroporation of sciatic nerve was associated with transient foot functional deficit that completely recovered at 30 days. Irreversible electroporation removed cells from trabeculae in the femurs of rabbits and in the vertebral body of sheep. After irreversible protocol, histology and microtomography demonstrated that the trabecular structure was maintained, the presence of new bone marrow cells, osteoblasts, and mineral apposition characterized by new trabeculae thinner than controls (P = .005) and a significant reduction in the ablated areas (-225%, P = .0219). Spinal cord, vertebral pedicles and spinal nerves showed transient edema in the absence of functional or structural alterations. Collectively, these results show that electroporation can be safely applied to bone even in the proximity of neuronal structures. PMID- 26351305 TI - Lymphoblastoid cell lines reveal associations of adult DNA methylation with childhood and current adversity that are distinct from whole blood associations. AB - BACKGROUND: Some cohort studies bank lymphoblastoid cell lines (LCLs) as a renewable source of participant DNA. However, although LCL DNA has proved valuable for genetic studies, its utility in epigenetic epidemiology research is unknown. METHODS: To assess whether LCL DNA can be used for life-course environmental epigenomics, we carried out a pilot methylomic study (using the Illumina Infinium Human Methylation 450 BeadChip) of nil-passage, Epstein-Barr virus (EBV)-transformed LCLs (n = 42) and 28 matched whole-blood (WB) samples. These were from adult male participants of the British 1958 birth cohort, selected for extremes of social economic position (SEP) in childhood and adulthood, with additional information available on childhood abuse and prenatal tobacco exposure. RESULTS: We identified a small number of weak associations between these exposures and methylation levels of both individual CpG sites and genomic regions in WB and LCLs. However, only one of the regional, and none of the individual CpG site associations were common to both sample types. The lack of overlap between the associations detected in LCL compared with those found in WB could either be due to the EBV-transformation process, or to the fact that, unlike WB, LCLs are essentially a single (CD19+) cell type. We provide evidence that the latter is the more potent explanation, by showing that CpG sites known to be differentially methylated between different types of blood cell have significantly lower correlations (R = 0.11) than average (R = 0.2) between WB and LCLs in our datasets, whereas sites known to be affected by EBV-transformation have significantly higher correlations (R = 0.3). CONCLUSIONS: This small pilot study suggests that the DNA methylation profile of LCLs is more closely related to that of B cells than WB and, additionally, that LCLs may nevertheless be useful for life-course environmental epigenomics. PMID- 26351306 TI - Effects of MVA85A vaccine on tuberculosis challenge in animals: systematic review. AB - BACKGROUND: The existing Bacillus Calmette-Guerin (BCG) vaccination provides partial protection against tuberculosis (TB). The modified vaccinia ankara virus expressing antigen 85A (MVA85A) aims to boost BCG immunity. We evaluated the animal evidence supporting the testing of MVA85A in humans. METHODS: Our protocol included in vivo preclinical studies of the MVA85A booster with BCG compared with BCG alone, followed by a TB challenge. We used standard methods for systematic review of animal studies, and summarized mortality, measures of pathology and lung bacterial load. The comprehensive literature search was to September 2014. Two independent investigators assessed eligibility and performed data extraction. We assessed study quality and pooled bacteria load using random effect meta analysis. FINDINGS: We included eight studies in 192 animals. Three experiments were in mice, two in guinea pigs, two in macaques and one in calves. Overall, study quality was low with no randomization, baseline comparability not described and blinding not reported. For animal death (including euthanasia due to severe morbidity), studies were underpowered, and overall no benefit demonstrated. No difference was shown for lung pathology measured on an ordinal scale or bacterial load. The largest mortality trial carried out in macaques had more deaths in the MVA85A vaccine group, and was published after a trial in South Africa had started recruiting children. CONCLUSIONS: This independent assessment of the animal data does not provide evidence to support efficacy of MVA85A as a BCG booster. More rigorous conduct and reporting of preclinical research are warranted, and we believe the results of studies should be publicly available before embarking on trials in humans, irrespective of the findings. PMID- 26351307 TI - A Specialized Histone H1 Variant Is Required for Adaptive Responses to Complex Abiotic Stress and Related DNA Methylation in Arabidopsis. AB - Linker (H1) histones play critical roles in chromatin compaction in higher eukaryotes. They are also the most variable of the histones, with numerous nonallelic variants cooccurring in the same cell. Plants contain a distinct subclass of minor H1 variants that are induced by drought and abscisic acid and have been implicated in mediating adaptive responses to stress. However, how these variants facilitate adaptation remains poorly understood. Here, we show that the single Arabidopsis (Arabidopsis thaliana) stress-inducible variant H1.3 occurs in plants in two separate and most likely autonomous pools: a constitutive guard cell-specific pool and a facultative environmentally controlled pool localized in other tissues. Physiological and transcriptomic analyses of h1.3 null mutants demonstrate that H1.3 is required for both proper stomatal functioning under normal growth conditions and adaptive developmental responses to combined light and water deficiency. Using fluorescence recovery after photobleaching analysis, we show that H1.3 has superfast chromatin dynamics, and in contrast to the main Arabidopsis H1 variants H1.1 and H1.2, it has no stable bound fraction. The results of global occupancy studies demonstrate that, while H1.3 has the same overall binding properties as the main H1 variants, including predominant heterochromatin localization, it differs from them in its preferences for chromatin regions with epigenetic signatures of active and repressed transcription. We also show that H1.3 is required for a substantial part of DNA methylation associated with environmental stress, suggesting that the likely mechanism underlying H1.3 function may be the facilitation of chromatin accessibility by direct competition with the main H1 variants. PMID- 26351308 TI - Epigenetic Mutation of RAV6 Affects Leaf Angle and Seed Size in Rice. AB - Heritable epigenetic variants of genes, termed epialleles, can broaden genetic and phenotypic diversity in eukaryotes. Epialleles may also provide a new source of beneficial traits for crop breeding, but very few epialleles related to agricultural traits have been identified in crops. Here, we identified Epi-rav6, a gain-of-function epiallele of rice (Oryza sativa) RELATED TO ABSCISIC ACID INSENSITIVE3 (ABI3)/VIVIPAROUS1 (VP1) 6 (RAV6), which encodes a B3 DNA-binding domain-containing protein. The Epi-rav6 plants show larger lamina inclination and smaller grain size; these agronomically important phenotypes are inherited in a semidominant manner. We did not find nucleotide sequence variation of RAV6. Instead, we found hypomethylation in the promoter region of RAV6, which caused ectopic expression of RAV6 in Epi-rav6 plants. Bisulfite analysis revealed that cytosine methylation of four CG and two CNG loci within a continuous 96-bp region plays essential roles in regulating RAV6 expression; this region contains a conserved miniature inverted repeat transposable element transposon insertion in cultivated rice genomes. Overexpression of RAV6 in the wild type phenocopied the Epi-rav6 phenotype. The brassinosteroid (BR) receptor BR INSENSITIVE1 and BR biosynthetic genes EBISU DWARF, DWARF11, and BR-DEFICIENT DWARF1 were ectopically expressed in Epi-rav6 plants. Also, treatment with a BR biosynthesis inhibitor restored the leaf angle defects of Epi-rav6 plants. This indicates that RAV6 affects rice leaf angle by modulating BR homeostasis and demonstrates an essential regulatory role of epigenetic modification on a key gene controlling important agricultural traits. Thus, our work identifies a unique rice epiallele, which may represent a common phenomenon in complex crop genomes. PMID- 26351309 TI - Distinct Regulatory Changes Underlying Differential Expression of TEOSINTE BRANCHED1-CYCLOIDEA-PROLIFERATING CELL FACTOR Genes Associated with Petal Variations in Zygomorphic Flowers of Petrocosmea spp. of the Family Gesneriaceae. AB - CYCLOIDEA (CYC)-like genes, belonging to the plant-specific TCP transcription factor family that is named after TEOSINTE BRANCHED1 (TB1) from maize (Zea mays), CYC from Antirrhinum majus, and the PROLIFERATING CELL FACTORS (PCF) from rice (Oryza sativa), have conserved dorsal identity function in patterning floral zygomorphy mainly through specific expression in dorsal petals of a flower. Their expression changes are usually related to morphological diversity of zygomorphic flowers. However, it is still a challenge to elucidate the molecular mechanism underlying their expression differentiation. It is also unknown whether CINCINNATA (CIN)-like TCP genes, locally controlling cell growth and proliferation, are involved in the evolution of floral zygomorphy. To address these questions, we selected two closely related species, i.e. Petrocosmea glabristoma and Petrocosmea sinensis, with distinct petal morphology to conduct expression, hybridization, mutant, and allele-specific expression analyses. The results show that the size change of the dorsal petals between the two species is mainly mediated by the expression differentiation of CYC1C and CYC1D, while the shape variation of all petals is related to the expression change of CIN1. In reciprocal F1 hybrids, the expression of CYC1C, CYC1D, and CIN1 conforms to an additive inheritance mode, consistent with the petal phenotypes of hybrids. Through allele-specific expression analyses, we find that the expression differentiation of these TCP genes is underlain by distinctly different types of regulatory changes. We suggest that highly redundant paralogs with identical expression patterns and interspecific expression differentiation may be controlled by remarkably different regulatory pathways because natural selection may favor different regulatory modifications rather than coding sequence changes of key developmental genes in generating morphological diversity. PMID- 26351310 TI - Renovascular hypertension: a case with atypical neurological signs. AB - Secondary hypertension is the most frequent form of hypertension in children. Renovascular disease accounts for 5-10% of all childhood hypertension and should be suspected in the presence of severe hypertension found difficult to manage with medical therapy. Uncontrolled hypertension can lead to severe target organ damage. We describe the case of a 13-month-old baby boy with failure to thrive, recent muscular weakness of the lower extremities and irritability. Hypertension was detected and he was admitted to the paediatric intensive care unit with a refractory hypertensive emergency, despite multiple antihypertensive therapies. Bilateral renal artery stenosis was diagnosed through renal angiography and balloon dilation was performed, leading to lower blood pressure. He is currently withdrawing from antihypertensive medication, and slowly gaining weight and recovering from target organ damage. However, weakness of the lower extremities persists and he has been diagnosed with a neurogenic bladder. PMID- 26351311 TI - Delayed relapse in pseudotumor cerebri due to new stenosis after transverse sinus stenting. AB - A patient presented with recurrent severe pseudotumor cerebri (PTC). Transverse sinus stenting is a very effective treatment option, however stenosis and intracranial hypertension can recur. In our patient, stenting initially resulted in resolution of papilloedema. However, after 5 years, a new stenosis developed which required further stenting. This case highlights the fact that, in patients with PTC who undergo transverse sinus stenting, a small proportion require repeat treatment due to formation of a new stenosis, usually adjacent to the existing stent. Patients with severe disease, such as ours, may be at higher risk of recurrence. Regardless of the severity, all patients who undergo stenting should have regular ocular follow-up. PMID- 26351312 TI - An unusual presentation of Guillain-Barre syndrome in a young man with bilateral upper extremity weakness. AB - A 30-year-old man attended the emergency department with a 4-day history of progressive, bilateral upper limb weakness. He had mild shortness of breath and occasional swallowing difficulties. One month prior to presentation, he had flu like symptoms and diarrhoea. Examination revealed upper limb hypotonia, symmetrical distal arm weakness and hyporeflexia. Power and reflexes in the lower limbs were normal. Nerve conduction studies and lumbar puncture demonstrated features consistent with Guillain-Barre syndrome (GBS). The patient was treated with a 5-day course of intravenous immunoglobulins. He improved significantly over the next 2 weeks. Breathing and swallow function did not deteriorate and required no further intervention. He had a sustained improvement, and remained at baseline 1 year later. Work-up for underlying structural, infectious, inflammatory and paraneoplastic aetiologies were negative. Serum antiganglioside antibodies were positive for the anti-GT1a IgG isotype supporting the clinical diagnosis of the pharyngeal-cervical-brachial variant of GBS. PMID- 26351313 TI - Synchronous endometrioid endometrial and ovarian cancer in a 34-year-old woman. AB - Ovarian cancer is the leading cause of death from gynaecological malignancy in developed countries. Synchronous endometrioid endometrial and ovarian cancer in patients appears with different clinical characteristics compared to patients with isolated endometrial cancer. A 34-year-old woman with lower abdominal pain of 1 year duration presented at the emergency department. On gynaecological examination, she had a left and midline pelvic mass. A transvaginal ultrasound showed it to be a complex hypervascularised mass, with cystic and solid components on left adnexal region. Ectopic pregnancy and pelvic inflammatory disease were excluded. Serum levels of tumour marker CA125 and ROMA were increased. The MR showed a complex mass, suggestive of primary fallopian tube or ovarian tumour. The patient underwent a total abdominal hysterectomy, bilateral salpingo-oophorectomy, pelvic and para-aortic lymph node dissection and subcolonic omentectomy. Histopathology revealed a synchronous endometrioid endometrial and ovarian cancer. PMID- 26351314 TI - Crizotinib-induced pancreatic pseudocyst: a novel adverse event. AB - Crizotinib is a tyrosine kinase inhibitor that demonstrates a dramatic tumour response in patients with advanced non-small cell lung cancers harbouring anaplastic lymphoma kinase (ALK) rearrangement. The pancreatic cyst has never been reported in patients who received crizotinib, whereas crizotinib-induced renal cysts developed in 4% of patients who were enrolled in clinical trials. We present the case of a 54-year-old man who was diagnosed with non-small cell lung cancer harbouring ALK rearrangement. After the start of treatment with crizotinib, we accidentally encountered the pancreatic pseudocyst without abdominal symptom and elevated serum pancreatic enzymes. In this report, we describe a case of pancreatic pseudocyst that appeared after starting treatment with crizotinib and regressed after treatment withdrawal. PMID- 26351315 TI - One ball or two? An unusual cause of hip pain. PMID- 26351316 TI - Hydropic leiomyoma of the uterus presenting as a giant abdominal mass. AB - We describe a case of a 35-year-old woman with a pedunculated uterine leiomyoma with diffuse hydropic degeneration presenting as a giant abdominal mass. The patient was admitted in the emergency department because of diffuse abdominal bloating and discomfort. Ultrasonography (US) showed a heterogeneous abdominopelvic mass. Magnetic resonance imaging (MRI) was performed to further characterise and revealed a myometrial pedunculated tumour. Despite its marked T2 signal heterogeneity and volume, there were no other suspicious findings to suggest a malignant nature; therefore, fertility-sparing myomectomy was performed. Leiomyomas frequently undergo degenerative changes altering their imaging appearances. Leiomyomas with uncommon degenerative changes may be difficult to differentiate from malignant myometrial tumours, based solely on imaging. To the best of our knowledge, a diffuse hydropic degeneration imaging appearance has only been described twice in the literature. We describe the imaging appearance of this rare form of leiomyoma drawing attention to its differential diagnosis. PMID- 26351317 TI - A history of recurrent wheezing can delay the diagnosis of foreign body aspiration in a paediatric emergency department. AB - Foreign body aspiration (FBA) into the airways is a potentially life-threatening event, and more frequent in children younger than 3 years of age; it can mimic other diseases by its frequently non-specific clinical and radiological presentation. The commonest misdiagnoses in children are asthma and recurrent respiratory tract infections with wheezing. This often makes it particularly difficult for a timely and proper diagnosis, especially when there is a silent history of FBA (not a rare occurrence in the age group at highest risk). We report a case of a 2-year-old boy who arrived at the emergency department at the Hospital of Ferrara, with dyspnoea, fever and wheezing, which had started 12 h after aspiration of a pistachio. The asymptomatic period after the pistachio aspiration, a history of recurrent wheezing during respiratory infections and the non-specificity of clinical and radiological findings, delayed the right diagnosis of FBA. PMID- 26351318 TI - Patterns of Atypical Functional Connectivity and Behavioral Links in Autism Differ Between Default, Salience, and Executive Networks. AB - Autism spectrum disorder (ASD) is characterized by atypical brain network organization, but findings have been inconsistent. While methodological and maturational factors have been considered, the network specificity of connectivity abnormalities remains incompletely understood. We investigated intrinsic functional connectivity (iFC) for four "core" functional networks default-mode (DMN), salience (SN), and left (lECN) and right executive control (rECN). Resting-state functional MRI data from 75 children and adolescents (37 ASD, 38 typically developing [TD]) were included. Functional connectivity within and between networks was analyzed for regions of interest (ROIs) and whole brain, compared between groups, and correlated with behavioral scores. ROI analyses showed overconnectivity (ASD > TD), especially between DMN and ECN. Whole-brain results were mixed. While predominant overconnectivity was found for DMN (posterior cingulate seed) and rECN (right inferior parietal seed), predominant underconnectivity was found for SN (right anterior insula seed) and lECN (left inferior parietal seed). In the ASD group, reduced SN integrity was associated with sensory and sociocommunicative symptoms. In conclusion, atypical connectivity in ASD is network-specific, ranging from extensive overconnectivity (DMN, rECN) to extensive underconnectivity (SN, lECN). Links between iFC and behavior differed between groups. Core symptomatology in the ASD group was predominantly related to connectivity within the salience network. PMID- 26351319 TI - Poly-ADP-Ribose Polymerase as a Therapeutic Target in Pediatric Diffuse Intrinsic Pontine Glioma and Pediatric High-Grade Astrocytoma. AB - Pediatric high-grade astrocytomas (pHGA) and diffuse intrinsic pontine gliomas (DIPG) are devastating malignancies for which no effective therapies exist. We investigated the therapeutic potential of PARP1 inhibition in preclinical models of pHGA and DIPG. PARP1 levels were characterized in pHGA and DIPG patient samples and tumor-derived cell lines. The effects of PARP inhibitors veliparib, olaparib, and niraparib as monotherapy or as radiosensitizers on cell viability, DNA damage, and PARP1 activity were evaluated in a panel of pHGA and DIPG cell lines. Survival benefit of niraparib was examined in an orthotopic xenograft model of pHGA. About 85% of pHGAs and 76% of DIPG tissue microarray samples expressed PARP1. Six of 8 primary cell lines highly expressed PARP1. Interestingly, across multiple cell lines, some PARP1 protein expression was required for response to PARP inhibition; however, there was no correlation between protein level or PARP1 activity and sensitivity to PARP inhibitors. Niraparib was the most effective at reducing cell viability and proliferation (MTT and Ki67). Niraparib induced DNA damage (gammaH2AX foci) and induced growth arrest. Pretreatment of pHGA cells with a sublethal dose of niraparib (1 MUmol/L) before 2 Gy of ionizing radiation (IR) decreased the rate of DNA damage repair, colony growth, and relative cell number. Niraparib (50 mg/kg) inhibited PARP1 activity in vivo and extended survival of mice with orthotopic pHGA xenografts, when administered before IR (20 Gy, fractionated), relative to control mice (40 vs. 25 days). Our data provide in vitro and in vivo evidence that niraparib may be an effective radiosensitizer for pHGA and DIPG. PMID- 26351320 TI - Targeting FGFR Pathway in Human Hepatocellular Carcinoma: Expressing pFGFR and pMET for Antitumor Activity. AB - The MET receptor tyrosine kinase, the receptor for hepatocyte growth factor (HGF), has been implicated in cancer growth, invasion, migration, angiogenesis, and metastasis in a broad variety of human cancers, including human hepatocellular carcinoma (HCC). Recently, MET was suggested to be a potential target for the personalized treatment of HCC with an active HGF-MET signaling pathway. However, the mechanisms of resistance to MET inhibitors need to be elucidated to provide effective treatment. Here, we show that HCC cells exhibit different sensitivities to the MET inhibitor PHA665752, depending on the phosphorylation status of FGFR. Treatment of cells expressing both phospho-FGFR and phospho-MET with the inhibitor PHA665752 did not cause growth inhibition and cell death, whereas treatment with AZD4547, a pan-FGFR inhibitor, resulted in decreased colony formation and cleavage of caspase-3. Moreover, silencing of endogenous FGFR1 and FGFR2 by RNAi of HCC cells expressing phospho-FGFR, phospho FGFR2, and phospho-MET overcame the resistance to PHA665752 treatment. Treatment of primary cancer cells from patients with HCC expressing both phospho-FGFR and phospho-MET with PHA665752 did not induce cell death, whereas AZD4547 treatment induced cell death through the cleavage of caspase-3. In addition, treatment of cells resistant to PHA665752 with AZD4547 abrogated the activation of downstream effectors of cell growth, proliferation, and survival. On the basis of these results, we conclude that the FGFR pathway is critical for HCC survival, and that targeting this pathway with AZD4547 may be beneficial for the treatment of patients with HCC-expressing phospho-FGFR and phospho-MET. PMID- 26351321 TI - Inhibition of ABCB1 Overcomes Cancer Stem Cell-like Properties and Acquired Resistance to MET Inhibitors in Non-Small Cell Lung Cancer. AB - Patients with non-small cell lung cancer (NSCLC) EGFR mutations have shown a dramatic response to EGFR inhibitors (EGFR-TKI). EGFR T790M mutation and MET amplification have been recognized as major mechanisms of acquired resistance to EGFR-TKI. Therefore, MET inhibitors have recently been used in NSCLC patients in clinical trials. In this study, we tried to identify the mechanism of acquired resistance to MET inhibitors. We analyzed the antitumor effects of two MET inhibitors, PHA-665752 and crizotinib, in 10 NSCLC cell lines. EBC-1 cells with MET amplification were the only cells that were sensitive to both MET inhibitors. We established PHA-665752-resistant EBC-1 cells, namely EBC-1R cells. Activation of KRAS, EGFR, and FGFR2 signaling was observed in EBC-1R cells by FISH and receptor tyrosine kinase phosphorylation antibody arrays. EBC-1R cells also showed overexpression of ATP-binding cassette subfamily B member 1 (ABCB1) as well as phosphorylation of MET. EBC-1R cells grew as cell spheres that exhibited cancer stem cell-like (CSC) properties and epithelial-mesenchymal transition (EMT). The level of miR-138 that targeted ABCB1 was decreased in EBC-1R cells. ABCB1 siRNA and the ABCB1 inhibitor elacridar could reduce sphere numbers and suppress EMT. Elacridar could also reverse resistance to PHA-665752 in EBC-1R cells. Our study demonstrated that ABCB1 overexpression, which was associated with CSC properties and EMT, was involved in the acquired resistance to MET inhibitors. Inhibition of ABCB1 might be a novel therapeutic strategy for NSCLC patients with acquired resistance to MET inhibitors. PMID- 26351322 TI - Combined Pan-RAF and MEK Inhibition Overcomes Multiple Resistance Mechanisms to Selective RAF Inhibitors. AB - RAF and MEK inhibitors are effective in BRAF-mutant melanoma but not in BRAF mutant colorectal cancer. To gain additional insights into this difference, we performed a genome-scale pooled shRNA enhancer screen in a BRAF-mutant, RAF inhibitor-resistant colorectal cancer cell line exposed to the selective RAF inhibitor PLX4720. We identified multiple genes along the receptor tyrosine kinase (RTK)/mitogen-activated protein kinase (MAPK) signaling axis that, when suppressed, either genetically or pharmacologically, sensitized cells to the selective RAF inhibitor through sustained inhibition of MAPK signaling. Strikingly, CRAF was a key mediator of resistance that could be overcome by the use of pan-RAF inhibitors in combination with a MEK inhibitor. Furthermore, the combination of pan-RAF and MEK inhibitors displayed strong synergy in melanoma and colorectal cancer cell lines with RAS-activating events such as RTK activation, KRAS mutation, or NF1 loss-of-function mutations. Combinations of selective RAF inhibitors, such as PLX4720 or dabrafenib, with MEK inhibitors did not incur such profound synergy, suggesting that inhibition of CRAF by pan-RAF inhibitors plays a key role in determining cellular response. Importantly, in contrast to the modest activity seen with single-agent treatment, dual pan-RAF and MEK inhibition results in the induction of apoptosis, greatly enhancing efficacy. Notably, combined pan-RAF and MEK inhibition can overcome intrinsic and acquired resistance to single-agent RAF/MEK inhibition, supporting dual pan-RAF and MEK inhibition as a novel therapeutic strategy for BRAF- and KRAS-mutant cancers. PMID- 26351323 TI - Tumors with AKT1E17K Mutations Are Rational Targets for Single Agent or Combination Therapy with AKT Inhibitors. AB - AKT1(E17K) mutations occur at low frequency in a variety of solid tumors, including those of the breast and urinary bladder. Although this mutation has been shown to transform rodent cells in culture, it was found to be less oncogenic than PIK3CA mutations in breast epithelial cells. Moreover, the therapeutic potential of AKT inhibitors in human tumors with an endogenous AKT1(E17K) mutation is not known. Expression of exogenous copies of AKT1(E17K) in MCF10A breast epithelial cells increased phosphorylation of AKT and its substrates, induced colony formation in soft agar, and formation of lesions in the mammary fat pad of immunodeficient mice. These effects were inhibited by the allosteric and catalytic AKT inhibitors MK-2206 and AZD5363, respectively. Both AKT inhibitors caused highly significant growth inhibition of breast cancer explant models with AKT1(E17K) mutation. Furthermore, in a phase I clinical study, the catalytic Akt inhibitor AZD5363 induced partial responses in patients with breast and ovarian cancer with tumors containing AKT1(E17K) mutations. In MGH-U3 bladder cancer xenografts, which contain both AKT1(E17K) and FGFR3(Y373C) mutations, AZD5363 monotherapy did not significantly reduce tumor growth, but tumor regression was observed in combination with the FGFR inhibitor AZD4547. The data show that tumors with AKT1(E17K) mutations are rational therapeutic targets for AKT inhibitors, although combinations with other targeted agents may be required where activating oncogenic mutations of other proteins are present in the same tumor. PMID- 26351324 TI - Sarcoma Cell Line Screen of Oncology Drugs and Investigational Agents Identifies Patterns Associated with Gene and microRNA Expression. AB - The diversity in sarcoma phenotype and genotype make treatment of this family of diseases exceptionally challenging. Sixty-three human adult and pediatric sarcoma lines were screened with 100 FDA-approved oncology agents and 345 investigational agents. The investigational agents' library enabled comparison of several compounds targeting the same molecular entity allowing comparison of target specificity and heterogeneity of cell line response. Gene expression was derived from exon array data and microRNA expression was derived from direct digital detection assays. The compounds were screened against each cell line at nine concentrations in triplicate with an exposure time of 96 hours using Alamar blue as the endpoint. Results are presented for inhibitors of the following targets: aurora kinase, IGF-1R, MEK, BET bromodomain, and PARP1. Chemical structures, IC50 heat maps, concentration response curves, gene expression, and miR expression heat maps are presented for selected examples. In addition, two cases of exceptional responders are presented. The drug and compound response, gene expression, and microRNA expression data are publicly available at http://sarcoma.cancer.gov. These data provide a unique resource to the cancer research community. PMID- 26351325 TI - Effective Inhibition of Bone Morphogenetic Protein Function by Highly Specific Llama-Derived Antibodies. AB - Bone morphogenetic proteins (BMP) have important but distinct roles in tissue homeostasis and disease, including carcinogenesis and tumor progression. A large number of BMP inhibitors are available to study BMP function; however, as most of these antagonists are promiscuous, evaluating specific effects of individual BMPs is not feasible. Because the oncogenic role of the different BMPs varies for each neoplasm, highly selective BMP inhibitors are required. Here, we describe the generation of three types of llama-derived heavy chain variable domains (VHH) that selectively bind to either BMP4, to BMP2 and 4, or to BMP2, 4, 5, and 6. These generated VHHs have high affinity to their targets and are able to inhibit BMP signaling. Epitope binning and docking modeling have shed light into the basis for their BMP specificity. As opposed to the wide structural reach of natural inhibitors, these small molecules target the grooves and pockets of BMPs involved in receptor binding. In organoid experiments, specific inhibition of BMP4 does not affect the activation of normal stem cells. Furthermore, in vitro inhibition of cancer-derived BMP4 noncanonical signals results in an increase of chemosensitivity in a colorectal cancer cell line. Therefore, because of their high specificity and low off-target effects, these VHHs could represent a therapeutic alternative for BMP4(+) malignancies. PMID- 26351327 TI - Determination of Rivaroxaban in Human Plasma by Solid-Phase Extraction-High Performance Liquid Chromatography. AB - In this study, a solid-phase extraction (SPE)-high performance liquid chromatography (HPLC)-ultra violet (UV) method was developed for the determination of rivaroxaban (RIV), an oral anticoagulant drug, in human plasma samples. The concentration of RIV in plasma samples was increased 7.5 times and the interference coming from matrix components was avoided by using SPE. The extracted samples of RIV were analyzed by using an HPLC-UV method. RIV was approved in 2008 and many studies have been published in recent years in order to investigate its pharmacokinetic profile in various groups. In light of this information, it is clear that the RIV pharmacokinetic profile should be investigated in further studies; the HPLC-UV method presented in this study might be an easy method to apply, as it is a cheap and rapid alternative to HPLC-MS-MS for this purpose. A Phenomenex Luna 5-um C18 100 A LC column (250 * 4.6 mm) was used for the separation of RIV and prednisolone (internal standard). The total analysis time was <6 min. The method was validated according to the FDA guidelines and can be proposed for pharmacokinetic studies of RIV. PMID- 26351326 TI - Single-Molecule Supercoil Relaxation Assay as a Screening Tool to Determine the Mechanism and Efficacy of Human Topoisomerase IB Inhibitors. AB - Human nuclear type IB topoisomerase (Top1) inhibitors are widely used and powerful anticancer agents. In this study, we introduce and validate a single molecule supercoil relaxation assay as a molecular pharmacology tool for characterizing therapeutically relevant Top1 inhibitors. Using this assay, we determined the effects on Top1 supercoil relaxation activity of four Top1 inhibitors; three clinically relevant: camptothecin, LMP-400, LMP-776 (both indenoisoquinoline derivatives), and one natural product in preclinical development, lamellarin-D. Our results demonstrate that Top1 inhibitors have two distinct effects on Top1 activity: a decrease in supercoil relaxation rate and an increase in religation inhibition. The type and magnitude of the inhibition mode depend both on the specific inhibitor and on the topology of the DNA substrate. In general, the efficacy of inhibition is significantly higher with supercoiled than with relaxed DNA substrates. Comparing single-molecule inhibition with cell growth inhibition (IC50) measurements showed a correlation between the binding time of the Top1 inhibitors and their cytotoxic efficacy, independent of the mode of inhibition. This study demonstrates that the single-molecule supercoil relaxation assay is a sensitive method to elucidate the detailed mechanisms of Top1 inhibitors and is relevant for the cellular efficacy of Top1 inhibitors. PMID- 26351328 TI - Walking the Tightrope Between Treatment Efficacy and Price. PMID- 26351329 TI - Reply to M.-E. Rouge Bugat et al. PMID- 26351330 TI - Immunology and Immunotherapy of Head and Neck Cancer. AB - The immune system plays a key role in the development, establishment, and progression of head and neck squamous cell carcinoma (HNSCC). A greater understanding of the dysregulation and evasion of the immune system in the evolution and progression of HNSCC provides the basis for improved therapies and outcomes for patients. HNSCC cells evade the host immune system through manipulation of their own immunogenicity, production of immunosuppressive mediators, and promotion of immunomodulatory cell types. Through the tumor's influence on the microenvironment, the immune system can be exploited to promote metastasis, angiogenesis, and growth. This article provides a brief overview of key components of the immune infiltrating cells in the tumor microenvironment, reviewing immunological principles related to head and neck cancer, including the concept of cancer immunosurveillance and immune escape. Current immunotherapeutic strategies and emerging results from ongoing clinical trials are presented. PMID- 26351331 TI - Overview of Advances in Head and Neck Cancer. PMID- 26351333 TI - Treatment of Small-Cell Lung Cancer: American Society of Clinical Oncology Endorsement of the American College of Chest Physicians Guideline. AB - PURPOSE: The American College of Chest Physicians (ACCP) produced an evidence based guideline on treatment of patients with small-cell lung cancer (SCLC). Because of the relevance of this guideline to American Society of Clinical Oncology (ASCO) membership, ASCO reviewed the guideline, applying a set of procedures and policies used to critically examine guidelines developed by other organizations. METHODS: The ACCP guideline on the treatment of SCLC was reviewed for developmental rigor by methodologists. An ASCO Endorsement Panel updated the literature search, reviewed the content, and considered additional recommendations. RESULTS: The ASCO Endorsement Panel determined that the recommendations from the ACCP guideline, published in 2013, are clear, thorough, and based on current scientific evidence. ASCO endorses the ACCP guideline on the treatment of SCLC, with the addition of qualifying statements. RECOMMENDATIONS: Surgery is indicated for selected stage I SCLC. Limited-stage disease should be treated with concurrent chemoradiotherapy in patients with good performance status. Thoracic radiotherapy should be administered early in the course of treatment, preferably beginning with cycle one or two of chemotherapy. Chemotherapy should consist of four cycles of a platinum agent and etoposide. Extensive-stage disease should be treated primarily with chemotherapy consisting of a platinum agent plus etoposide or irinotecan. Prophylactic cranial irradiation prolongs survival in patients with limited-stage disease who achieve a complete or partial response to initial therapy and may do so in similarly responding patients with extensive-stage disease as well. Additional information is available at http://www.asco.org/endorsements/sclc and http://www.asco.org/guidelineswiki. PMID- 26351332 TI - Cost-Effectiveness of Pertuzumab in Human Epidermal Growth Factor Receptor 2 Positive Metastatic Breast Cancer. AB - PURPOSE: The Clinical Evaluation of Pertuzumab and Trastuzumab (CLEOPATRA) study showed a 15.7-month survival benefit with the addition of pertuzumab to docetaxel and trastuzumab (THP) as first-line treatment for patients with human epidermal growth factor receptor 2 (HER2) -overexpressing metastatic breast cancer. We performed a cost-effectiveness analysis to assess the value of adding pertuzumab. PATIENT AND METHODS: We developed a decision-analytic Markov model to evaluate the cost effectiveness of docetaxel plus trastuzumab (TH) with or without pertuzumab in US patients with metastatic breast cancer. The model followed patients weekly over their remaining lifetimes. Health states included stable disease, progressing disease, hospice, and death. Transition probabilities were based on the CLEOPATRA study. Costs reflected the 2014 Medicare rates. Health state utilities were the same as those used in other recent cost-effectiveness studies of trastuzumab and pertuzumab. Outcomes included health benefits expressed as discounted quality-adjusted life-years (QALYs), costs in US dollars, and cost effectiveness expressed as an incremental cost-effectiveness ratio. One- and multiway deterministic and probabilistic sensitivity analyses explored the effects of specific assumptions. RESULTS: Modeled median survival was 39.4 months for TH and 56.9 months for THP. The addition of pertuzumab resulted in an additional 1.81 life-years gained, or 0.62 QALYs, at a cost of $472,668 per QALY gained. Deterministic sensitivity analysis showed that THP is unlikely to be cost effective even under the most favorable assumptions, and probabilistic sensitivity analysis predicted 0% chance of cost effectiveness at a willingness to pay of $100,000 per QALY gained. CONCLUSION: THP in patients with metastatic HER2-positive breast cancer is unlikely to be cost effective in the United States. PMID- 26351334 TI - Advances in Supportive Care for Late Effects of Head and Neck Cancer. AB - As the population of head and neck cancer survivors increases, it has become increasingly important for health care providers to understand and manage late complications of therapy. Functional deficits can be categorized as general health deficits resulting in frailty or debility, head and neck-specific functional deficits such as swallowing and speech, and musculoskeletal impairment as a result of tumor and treatment. Of critical importance is the growing data indicating that swallow therapy and physical therapy may prevent or ameliorate long-term functional deficits. Oral health complications of head and neck therapy may manifest months or years after the completion of treatment. Patients with hyposalivation are at high risk for dental caries and thus require aggressive oral hygiene regimens and routine dental surveillance. Swallowing abnormalities, xerostomia, and poor dentition may result in dietary adaptations that may cause nutritional deficiencies. Identification and management of maladaptive dietary strategies are important for long-term health. Follow-up with primary care physicians for management of comorbidities such as diabetes and hyperlipidemia may help to limit late vascular complications caused by radiation therapy. Herein, we review late effects of head and neck cancer therapy, highlighting recent advances. PMID- 26351336 TI - Survivorship and Quality of Life in Head and Neck Cancer. AB - Head and neck cancer is becoming more common, and survival rates are improving. Human papillomavirus-associated oropharyngeal cancer, in particular, is increasing in incidence and is associated with an excellent prognosis. However, toxicity from disease and treatment leads to long-term impairment, disability, and handicap. Currently, more than 60% of survivors have unmet needs. As the numbers of survivors increase, current models of care will be increasingly inadequate to meet their needs. Exploration of new strategies and models of care to better address quality-of-life issues and meet the needs of survivors of head and neck cancer is urgently required. PMID- 26351335 TI - Oral Cavity Carcinoma: Current Management, Controversies, and Future Directions. AB - Oral cavity carcinoma (OCC) remains a major cause of morbidity and mortality in patients with head and neck cancer. Although the incidence has decreased over the last decade, outcomes remain stagnant with only a 5% improvement in overall survival in the last 20 years. Although surgical resection remains the primary treatment modality, several areas of controversy exist with regard to work-up, management of the primary and neck tumors, and adjuvant therapy. As surgical techniques evolve, so has the delivery of radiotherapy and systemic treatment, which have helped to improve the outcomes for patients with advanced disease. Recently, the addition of cetuximab has shown promise as a way to improve outcomes while minimizing toxicity, and this remains an active area of study in the adjuvant setting. Advances in microvascular free-flap reconstruction have extended the limits of resection and enabled enhanced restoration of function and cosmesis. While these advances have led to limited survival benefit, evaluation of alternative modalities has gained interest on the basis of success in other head and neck subsites. Organ preservation with definitive chemoradiotherapy, though proven in the larynx and pharynx, remains controversial in OCC. Likewise, although the association of human papillomavirus is well established in oropharyngeal carcinoma, it has not been proven in the pathogenesis or survival of OCC. Future study of the molecular biology and pathogenesis of OCC should offer additional insight into screening, treatment selection, and novel therapeutic approaches. PMID- 26351337 TI - Transoral Endoscopic Head and Neck Surgery and Its Role Within the Multidisciplinary Treatment Paradigm of Oropharynx Cancer: Robotics, Lasers, and Clinical Trials. AB - Transoral endoscopic head and neck surgery is a new approach for the treatment of oropharyngeal tumors. Using either a robotic system and/or laser, surgeons gain access through the mouth via minimally invasive technique and thus have improved visualization of the tumors of the oropharynx, without disfiguring incisions. This transoral route of access minimizes long-term speech and swallowing dysfunction. Surgeons view this approach as a considerable technologic advance, analogous to the evolution in radiation therapy from conventional two- and three dimensional conformal techniques to intensity-modulated techniques. Although the use of radiation with or without chemotherapy to treat oropharyngeal cancer (OPC) is supported by evidence from prospective clinical trials, there are no prospective data supporting the use of this new surgical approach for OPC. Here, we review the fundamentals of transoral endoscopic head and neck surgery, with robotics and laser technology, and discuss ongoing clinical trials for patients with OPC. PMID- 26351338 TI - Epidemiology of Human Papillomavirus-Positive Head and Neck Squamous Cell Carcinoma. AB - Human papillomavirus (HPV) is now established as the principal cause of an increase in incidence of a subset of head and neck squamous cell cancers (HNCs) in numerous geographic regions around the world. Further study of the epidemiology of HPV-positive HNC will be critical to the development and implementation of public health interventions to reverse these global incidence trends. Here, recent data are reviewed to provide insight into several topics, including incidence trends and projections for HPV-positive HNC; the worldwide HPV-attributable fraction; sex disparities in cancer risk; the epidemiology of oral HPV infection; the latency period between infection and cancer; the potential impact of prophylactic HPV vaccination; and prospects for secondary prevention through screening for oral HPV infection or seroreactivity to viral antigens. The identification of a single necessary cause for any cancer provides a rare and perhaps extraordinary opportunity for cancer prevention. PMID- 26351339 TI - Organ Preservation for Advanced Larynx Cancer: Issues and Outcomes. AB - PURPOSE: To provide a review of the clinical data, controversies, and limitations that underpin current recommendations for approaches to larynx preservation for locally advanced larynx cancer requiring total laryngectomy. METHODS: The key findings from pivotal randomized controlled trials are discussed, including quality of life, late effects, and function assessments. Trials investigating taxane inclusion in induction chemotherapy and trials of epidermal growth factor receptor inhibition for radiosensitization are put into perspective for larynx cancer. Controversies in the management of T4 primaries and the opportunities for conservation laryngeal surgery are reviewed. RESULTS: There are data from clinical trials to support induction chemotherapy, followed by radiotherapy (preferred approach in Europe) and concomitant cisplatin plus radiotherapy (preferred in North America) for nonsurgical preservation of the larynx. Treatment intensification by a sequential approach of induction, followed by concomitant treatment, is investigational. Transoral laryngeal microsurgery and transoral robotic partial laryngectomy have application in selected patients. CONCLUSION: The management of locally advanced larynx cancer is challenging and requires an experienced multidisciplinary team for initial evaluation, response assessment, and support during and after treatment to achieve optimal function, quality of life, and overall survival. Patient expectations, in addition to tumor extent, pretreatment laryngeal function, and coexisting chronic disease, are critical factors in selecting surgical or nonsurgical primary treatment. PMID- 26351340 TI - Nasopharyngeal Cancer: Molecular Landscape. AB - Nasopharyngeal carcinoma (NPC) is a unique epithelial malignancy arising from the superior aspect of the pharyngeal mucosal space, associated with latent Epstein Barr virus infection in most cases. The capacity to characterize cancer genomes in unprecedented detail is now providing insights into the genesis and molecular underpinnings of this disease. Herein, we provide an overview of the molecular aberrations that likely drive nasopharyngeal tumor development and progression. The contributions of major Epstein-Barr virus-encoded factors, including proteins, small RNAs, and microRNAs, along with their interactions with pathways regulating cell proliferation and survival are highlighted. We review recent analyses that clearly define the role of genetic and epigenetic variations affecting the human genome in NPC. These findings point to the impact of DNA methylation and histone modifications on gene expression programs that promote this malignancy. The molecular interactions that allow NPC cells to evade immune recognition and elimination, which is crucial for the survival of cells expressing potentially immunogenic viral proteins, are also described. Finally, the potential utility of detecting host and viral factors for the diagnosis and prognosis of NPC is discussed. Altogether, the studies summarized herein have greatly expanded our knowledge of the molecular biology of NPC, yet much remains to be uncovered. Emerging techniques for using and analyzing well-annotated biospecimens from patients with NPC will ultimately lead to a greater level of understanding, and enable improvements in precision therapies and clinical outcomes. PMID- 26351341 TI - Current Treatment Options for Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma. AB - This review highlights the evidence-based data to support current best management practices for patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Current limitations and areas of emerging therapeutics are also emphasized. The cornerstone of palliation for patients with R/M HNSCC is a platinum-based backbone. Platinum doublets induce higher response rates than single agents but do not demonstrate a survival advantage and are associated with increased toxicity. The only regimen to demonstrate survival superiority is platinum, fluorouracil, and cetuximab, a monoclonal antibody directed against the epidermal growth factor receptor (EGFR). EGFR inhibitors, including monoclonal antibodies and tyrosine kinase inhibitors, have achieved only modest success in R/M HNSCC, illustrating the importance of identifying predictive biomarkers and finding ways to overcome mechanisms of resistance. Although phosphoinositide 3-kinase pathway alterations are present at a high rate in HNSCC, the identification of efficacious agents in patients with activating alterations has yet to be discovered. Immunotherapy represents an attractive treatment strategy for R/M HNSCC, with promising preliminary data from studies involving immune checkpoint blockade and toll-like receptor agonists. Human papillomavirus has a prognostic role in R/M disease; therefore, stratification of patients by human papillomavirus status in clinical trials is indicated. Although under-represented in clinical trials, elderly patients experience similar survival outcomes compared with younger patients, albeit with increased toxicity. Despite therapeutic advances, prognosis nonetheless remains poor for patients with R/M HNSCC. Enrollment of patients onto clinical trials to investigate novel therapeutics and identify predictive biomarkers is necessary to further refine and improve outcomes. PMID- 26351342 TI - Sex: Taboos, Assumptions, and Evidence. PMID- 26351343 TI - Human Papillomavirus-Associated Oropharyngeal Cancer: Defining Risk Groups and Clinical Trials. AB - Human papillomavirus-associated oropharynx cancer (HPVA-OPC) is rapidly increasing in incidence and has unique epidemiologic, molecular, and biologic characteristics. Despite being recognized as having superior prognosis, current evidence does not support less intense therapy compared with HPV-negative OPC. Current combined modality therapies confer a significant risk of morbidity, and patients with HPVA-OPC have a younger median age. These patients, therefore, live longer with the adverse effects of treatment, and this spurs the development of treatment deintensification trials that attempt to decrease treatment-related morbidity without compromising efficacy. Many radiation and chemotherapy de escalation trials are underway. Minimally invasive surgical techniques are also being evaluated. It is important to identify the ideal patient group for treatment deintensification and to define prognostic risk groups to avoid undertreating the poorer-risk subset in HPVA-OPC, and validated biomarkers are needed to identify patients with the best prognosis. Significant smoking exposure mitigates the favorable prognosis of HPVA-OPC. Currently, less intense treatment is an option only in the setting of clinical trials, and patients with HPVA-OPC should be offered clinical trial options whenever they are available. Finally, recognition of novel therapeutic targets and signaling pathways is critical to the development of new treatment strategies that are desperately needed for patients with poor risk and those with recurrent and metastatic disease. PMID- 26351344 TI - Randomized, Double-Blind, Phase II Study of Ruxolitinib or Placebo in Combination With Capecitabine in Patients With Metastatic Pancreatic Cancer for Whom Therapy With Gemcitabine Has Failed. AB - PURPOSE: Patients with advanced pancreatic adenocarcinoma have a poor prognosis and limited second-line treatment options. Evidence suggests a role for the Janus kinase (JAK)/signal transducer and activator of transcription pathway in the pathogenesis and clinical course of pancreatic cancer. PATIENTS AND METHODS: In this double-blind, phase II study, patients with metastatic pancreatic cancer who had experienced treatment failure with gemcitabine were randomly assigned 1:1 to the JAK1/JAK2 inhibitor ruxolitinib (15 mg twice daily) plus capecitabine (1,000 mg/m(2) twice daily) or placebo plus capecitabine. The primary end point was overall survival (OS); secondary end points included progression-free survival, clinical benefit response, objective response rate, and safety. Prespecified subgroup analyses evaluated treatment heterogeneity and efficacy in patients with evidence of inflammation. RESULTS: In the intent-to-treat population (ruxolitinib, n = 64; placebo, n = 63), the hazard ratio was 0.79 (95% CI, 0.53 to 1.18; P = .25) for OS and was 0.75 (95% CI, 0.52 to 1.10; P = .14) for progression-free survival. In a prespecified subgroup analysis of patients with inflammation, defined by serum C-reactive protein levels greater than the study population median (ie, 13 mg/L), OS was significantly greater with ruxolitinib than with placebo (hazard ratio, 0.47; 95% CI, 0.26 to 0.85; P = .011). Prolonged survival in this subgroup was supported by post hoc analyses of OS that categorized patients by the modified Glasgow Prognostic Score, a systemic inflammation-based prognostic system. Grade 3 or greater adverse events were observed with similar frequency in the ruxolitinib (74.6%) and placebo (81.7%) groups. Grade 3 or greater anemia was more frequent with ruxolitinib (15.3%; placebo, 1.7%). CONCLUSION: Ruxolitinib plus capecitabine was generally well tolerated and may improve survival in patients with metastatic pancreatic cancer and evidence of systemic inflammation. PMID- 26351345 TI - Feasibility of Preoperative Chemotherapy With or Without Radiation Therapy in Localized Soft Tissue Sarcomas of Limbs and Superficial Trunk in the Italian Sarcoma Group/Grupo Espanol de Investigacion en Sarcomas Randomized Clinical Trial: Three Versus Five Cycles of Full-Dose Epirubicin Plus Ifosfamide. AB - PURPOSE: We report on feasibility of preoperative chemotherapy with or without radiation therapy (RT) in the context of a phase III randomized clinical trial involving localized, high-risk, soft tissue sarcomas. PATIENTS AND METHODS: Of 321 eligible patients, 161 were randomly assigned to three preoperative cycles of epirubicin 120 mg/m(2) plus ifosfamide 9 g/m(2), and 160 were randomly assigned to three preoperative plus two postoperative cycles. Among them, 303 patients were included in this analysis; 169 were male and 134 were female, with a median age of 48 years (range, 15 to 79 years). One hundred fifty-two patients received concurrent RT preoperatively at a total dose of 44 to 50 Gy. Preoperative chemotherapy-related hematologic toxicity and early postoperative complications were reported. The influence of RT, age, and sex on hematologic grade 3 or 4 toxicities and wound complications was analyzed. Chemotherapeutic dose intensity (DI) was analyzed. RESULTS: Among the patients, 61.4%, 22.4%, and 23.8% experienced, grade 4 leucopenia, grade 3 or 4 anemia, and grade 3 or 4 thrombocytopenia, respectively. Respective rates were 66.4%, 24.3%, and 31.6% when RT was added preoperatively, and 56.3%, 20.5%, and 15.9% when preoperative chemotherapy was administered alone. Patient age affected grade 3 or 4 thrombocytopenia. Grade 4 leucopenia and grade 3 or 4 anemia presented 2.5 times more frequently in female patients than in male patients. Wound complications were observed in 13.5% of patients: 17% with preoperative RT and 10% without. Chemotherapeutic DI was greater than 90%, even in patients receiving preoperative RT and in patients age 65 years or older. CONCLUSION: This preoperative chemotherapy is feasible and can also be proposed for selected elderly patients. Grade 3 or 4 hematologic toxicity was common, but DI was excellent. Concurrent preoperative RT is safe, although an increased rate of grade 4 thrombocytopenia and limited increase in wound complications may be observed. PMID- 26351346 TI - Polypharmacy and Potentially Inappropriate Medication Use Among Senior Adults With Cancer: What Is the Best Approach? PMID- 26351347 TI - Human Papillomavirus-Negative Pharyngeal Cancer. AB - Human papillomavirus-negative head and neck squamous cell carcinoma (HNSCC) carries a poor prognosis, and despite optimal treatment with chemoradiotherapy to the limit of tolerance, many patients will relapse. A number of methods for intensifying treatment of HNSCC have been investigated, leading to the current standards of care. Novel agents targeting tumor cell and stromal signaling, DNA damage response, and immune system are now reaching clinical trials in combination with chemoradiotherapy. In this review, we discuss the evidence for the current treatment of locally advanced human papillomavirus-negative HNSCC, as well as investigational therapies, such as hypoxia modification, molecular targeting of epidermal growth factor receptor family, vascular endothelial growth factor receptor or DNA damage response proteins in combination with radiation therapy. PMID- 26351348 TI - Nonmelanoma Cutaneous Head and Neck Cancer and Merkel Cell Carcinoma: Current Concepts, Advances, and Controversies. AB - Nonmelanoma skin cancer (NMSC) is the most common cancer worldwide and the most frequently observed malignancy in whites. Approximately 75% to 80% are basal cell carcinomas and 20% to 25% are squamous cell carcinomas. Incidence is increasing, partly reflecting an ageing population, and NMSC is more commonly seen in men. The predominant causative agent is ultraviolet solar radiation exposure, with the majority of cases occurring on the head and neck. Surgical excision is typically the treatment of choice, providing histopathologic information, high cure rates, and acceptable cosmetic and functional outcomes. Radiation therapy is reserved for cases where surgery is not the preferred choice or for high-risk cases where adjuvant therapy is recommended. Although overall mortality rates are low, patients with complex cases such as those with immunosuppression should be considered for management within multidisciplinary tumor boards. In contrast, Merkel cell carcinoma is a rare and aggressive malignancy, frequently arising on the head and neck in older whites, with a poorer prognosis. This article focuses on the current evidence guiding practice, recent advances, and areas of controversy in NMSC and Merkel cell carcinoma of the head and neck. PMID- 26351349 TI - Safety and Antitumor Activity of Anti-PD-1 Antibody, Nivolumab, in Patients With Platinum-Resistant Ovarian Cancer. AB - PURPOSE: Programmed death-1 (PD-1), a coinhibitory immune signal receptor expressed in T cells, binds to PD-1 ligand and regulates antitumor immunity. Nivolumab is an anti-PD-1 antibody that blocks PD-1 signaling. We assessed the safety and antitumor activity of nivolumab in patients with platinum-resistant ovarian cancer. PATIENTS AND METHODS: Twenty patients with platinum-resistant ovarian cancer were treated with an intravenous infusion of nivolumab every 2 weeks at a dose of 1 or 3 mg/kg (constituting two 10-patient cohorts) from October 21, 2011. This phase II trial defined the primary end point as the best overall response. Patients received up to six cycles (four doses per cycle) of nivolumab treatment or received doses until disease progression occurred. Twenty nivolumab-treated patients were evaluated at the end of the trial on December 7, 2014. RESULTS: Grade 3 or 4 treatment-related adverse events occurred in eight (40%) of 20 patients. Two patients had severe adverse events. In the 20 patients in whom responses could be evaluated, the best overall response was 15%, which included two patients who had a durable complete response (in the 3-mg/kg cohort). The disease control rate in all 20 patients was 45%. The median progression-free survival time was 3.5 months (95% CI, 1.7 to 3.9 months), and the median overall survival time was 20.0 months (95% CI, 7.0 months to not reached) at study termination. CONCLUSION: This study, to our knowledge, is the first to explore the effects of nivolumab against ovarian cancer. The encouraging safety and clinical efficacy of nivolumab in patients with platinum-resistant ovarian cancer indicate the merit of additional large-scale investigations (UMIN Clinical Trials Registry UMIN000005714). PMID- 26351351 TI - Management of Squamous Cancer Metastatic to Cervical Nodes With an Unknown Primary Site. AB - Squamous cell carcinoma of an unknown primary (SCCUP) of the head and neck is a rare disease. As a diagnosis of exclusion, the manner in which it is assigned merits consideration. Despite the development and refinement of several techniques designed to locate an occult tumor, including cross-sectional anatomic imaging, functional imaging, and transoral surgical techniques, delineating SCCUP remains an active clinical problem. Its relative rarity has prevented prospective study of the entity. Hence, investigators must rely on retrospective analyses to understand the disease and its appropriate treatment. The current understanding of SCCUP differs substantially from when it was initially described decades ago. The most common site of a small primary tumor initially thought to represent SCCUP is the tonsil or base of the tongue, and an increasing percentage are associated with human papilloma virus. Modern treatment of SCCUP by neck dissection alone, neck dissection followed by radiation with or without concurrent chemotherapy, or primary chemoradiation according to initial nodal disease burden produces extraordinarily low recurrence rates. Whether the potential mucosal primary site and/or the contralateral neck should be electively treated is controversial. Efficacy data seem to be similar; therefore, an evaluation of the toxicity of both treatment paradigms is warranted. PMID- 26351350 TI - Randomized, Placebo-Controlled, Phase III Trial of Yeast-Derived Granulocyte Macrophage Colony-Stimulating Factor (GM-CSF) Versus Peptide Vaccination Versus GM-CSF Plus Peptide Vaccination Versus Placebo in Patients With No Evidence of Disease After Complete Surgical Resection of Locally Advanced and/or Stage IV Melanoma: A Trial of the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network Cancer Research Group (E4697). AB - PURPOSE: We conducted a double-blind, placebo-controlled trial to evaluate the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) and peptide vaccination (PV) on relapse-free survival (RFS) and overall survival (OS) in patients with resected high-risk melanoma. PATIENTS AND METHODS: Patients with completely resected stage IV or high-risk stage III melanoma were grouped by human leukocyte antigen (HLA) -A2 status. HLA-A2-positive patients were randomly assigned to receive GM-CSF, PV, both, or placebo; HLA-A2-negative patients, GM CSF or placebo. Treatment lasted for 1 year or until recurrence. Efficacy analyses were conducted in the intent-to-treat population. RESULTS: A total of 815 patients were enrolled. There were no significant improvements in OS (stratified log-rank P = .528; hazard ratio, 0.94; 95% repeated CI, 0.77 to 1.15) or RFS (P = .131; hazard ratio, 0.88; 95% CI, 0.74 to 1.04) in the patients assigned to GM-CSF (n = 408) versus those assigned to placebo (n = 407). The median OS times with GM-CSF versus placebo treatments were 69.6 months (95% CI, 53.4 to 83.5 months) versus 59.3 months (95% CI, 44.4 to 77.3 months); the 5-year OS probability rates were 52.3% (95% CI, 47.3% to 57.1%) versus 49.4% (95% CI, 44.3% to 54.3%), respectively. The median RFS times with GM-CSF versus placebo were 11.4 months (95% CI, 9.4 to 14.8 months) versus 8.8 months (95% CI, 7.5 to 11.2 months); the 5-year RFS probability rates were 31.2% (95% CI, 26.7% to 35.9%) versus 27.0% (95% CI, 22.7% to 31.5%), respectively. Exploratory analyses showed a trend toward improved OS in GM-CSF-treated patients with resected visceral metastases. When survival in HLA-A2-positive patients who received PV versus placebo was compared, RFS and OS were not significantly different. Treatment-related grade 3 or greater adverse events were similar between GM-CSF and placebo groups. CONCLUSION: Neither adjuvant GM-CSF nor PV significantly improved RFS or OS in patients with high-risk resected melanoma. Exploratory analyses suggest that GM-CSF may be beneficial in patients with resected visceral metastases; this observation requires prospective validation. PMID- 26351352 TI - Oncologic Surveillance After Surgical Resection for Renal Cell Carcinoma: A Novel Risk-Based Approach. AB - PURPOSE: The appropriate duration of surveillance for renal cell carcinoma (RCC) after radical or partial nephrectomy remains unknown, and evidence to support current guidelines are lacking. Herein, we provide an approach to surveillance that balances the risk of recurrence versus the risk of non-RCC death. PATIENTS AND METHODS: We identified 2,511 patients who underwent surgery for M0 RCC between 1990 and 2008. Patients were stratified for analysis by pathologic stage (pT1Nx-0, pT2Nx-0, pT3/4Nx-0, and pTanyN1), relapse location (abdomen, chest, bone, and other), age (< 50, 50 to 59, 60 to 69, 70-79 and >= 80 years), and Charlson comorbidity index (CCI; <= 1 and >= 2). Risks of disease recurrence and non-RCC death were estimated by using parametric models for time-to-failure with Weibull distributions. Surveillance duration was estimated at the point when the risk of non-RCC death exceeded the risk of recurrence. RESULTS: At a median follow-up of 9.0 years (interquartile range, 6.4 to 12.7 years), a total of 676 patients developed recurrence. By using a competing-risk model, vastly different surveillance durations were appreciated. Specifically, among patients with pT1Nx 0 disease and a CCI <= 1, risk of non-RCC death exceeded that of abdominal recurrence risk at 6 months in patients age 80 years and older but failed to do so for greater than 20 years in patients younger than age 50 years. For patients with pT1Nx-0 disease but a CCI >= 2, the risk of non-RCC death exceeded that of abdominal recurrence risk already at 30 days after surgery, regardless of patient age. CONCLUSION: We present an individualized approach to RCC surveillance that bases the duration of follow-up on the interplay between competing risk factors of recurrence and non-RCC death. This strategy may improve the balance between the derived benefit from surveillance and medical resource allocation. PMID- 26351353 TI - Genetic Landscape of Human Papillomavirus-Associated Head and Neck Cancer and Comparison to Tobacco-Related Tumors. AB - Head and neck cancer is the fifth most common cancer worldwide. It is often amenable to curative intent therapy when localized to the head and neck region, but it carries a poor prognosis when it is recurrent or metastatic. Therefore, initial treatment decisions are critical to improve patient survival. However, multimodality therapy used with curative intent is toxic. The balance between offering intensive versus tolerable and function-preserving therapy has been thrown into sharp relief with the recently described epidemic of human papillomavirus-associated head and neck squamous cell carcinomas characterized by improved clinical outcomes compared with smoking-associated head and neck tumors. Model systems and clinical trials have been slow to address the clinical questions that face the field to date. With this as a background, a host of translational studies have recently reported the somatic alterations in head and neck cancer and have highlighted the distinct genetic and biologic differences between viral and tobacco-associated tumors. This review seeks to summarize the main findings of studies, including The Cancer Genome Atlas, for the clinician scientist, with a goal of leveraging this new knowledge toward the betterment of patients with head and neck cancer. PMID- 26351354 TI - Advances in Radiotherapy for Head and Neck Cancer. AB - Over the last few decades, significant improvements have been made in the radiotherapy (RT) treatment of head and neck malignancies. The progressive introduction of intensity-modulated RT and the use of multimodality imaging for target volume and organs at risk delineation, together with the use of altered fractionation regimens and concomitant administration of chemotherapy or targeted agents, have accompanied efficacy improvements in RT. Altogether, such improvements have translated into improvement in locoregional control and overall survival probability, with a decrease in the long-term adverse effects of RT and an improvement in quality of life. Further progress in the treatment of head and neck malignancies may come from a better integration of molecular imaging to identify tumor subvolumes that may require additional radiation doses (ie, dose painting) and from treatment adaptation tracing changes in patient anatomy during treatment. Proton therapy generates even more exquisite dose distribution in some patients, thus potentially further improving patient outcomes. However, the clinical benefit of these approaches, although promising, for patients with head and neck cancer need to be demonstrated in prospective randomized studies. In this context, our article will review some of these advances, with special emphasis on target volume and organ-at-risk delineation, use of molecular imaging for tumor delineation, dose painting for dose escalation, dose adaptation throughout treatment, and potential benefit of proton therapy. PMID- 26351355 TI - Management of Nasopharyngeal Carcinoma: Current Practice and Future Perspective. AB - Nasopharyngeal carcinoma of the undifferentiated subtype is endemic to southern China, and patient prognosis has improved significantly over the past three decades because of advances in disease management, diagnostic imaging, radiotherapy technology, and broader application of systemic therapy. Despite the excellent local control with modern radiotherapy, distant failure remains a key challenge. Advances in molecular technology have helped to decipher the molecular pathogenesis of nasopharyngeal carcinoma as well as its etiologic association with the Epstein-Barr virus. This in turn has led to the discovery of novel biomarkers and drug targets, rendering this cancer site a current focus for new drug development. This article reviews and appraises the key literature on the current management of nasopharyngeal carcinoma and future directions in clinical research. PMID- 26351357 TI - Research Reconstructed: Strategies to Conduct Research With Limited Funding. PMID- 26351356 TI - KNOTTED1-LIKE HOMEOBOX 3: a new regulator of symbiotic nodule development. AB - KNOX transcription factors (TFs) regulate different aspects of plant development essentially through their effects on phytohormone metabolism. In particular, KNOX TF SHOOTMERISTEMLESS activates the cytokinin biosynthesis ISOPENTENYL TRANSFERASE (IPT) genes in the shoot apical meristem. However, the role of KNOX TFs in symbiotic nodule development and their possible effects on phytohormone metabolism during nodulation have not been studied to date. Cytokinin is a well known regulator of nodule development, playing the key role in the regulation of cell division during nodule primordium formation. Recently, the activation of IPT genes was shown to take place during nodulation. Therefore, it was hypothesized that KNOX TFs may regulate nodule development and activate cytokinin biosynthesis upon nodulation. This study analysed the expression of different KNOX genes in Medicago truncatula Gaertn. and Pisum sativum L. Among them, the KNOX3 gene was upregulated in response to rhizobial inoculation in both species. pKNOX3::GUS activity was observed in developing nodule primordium. KNOX3 ectopic expression caused the formation of nodule-like structures on transgenic root without bacterial inoculation, a phenotype similar to one described previously for legumes with constitutive activation of the cytokinin receptor. Furthermore, in transgenic roots with MtKNOX3 knockdown, downregulation of A-type cytokinin response genes was found, as well as the MtIPT3 and LONELYGUY2 (MtLOG2) gene being involved in cytokinin activation. Taken together, these findings suggest that KNOX3 gene is involved in symbiotic nodule development and may regulate cytokinin biosynthesis/activation upon nodule development in legume plants. PMID- 26351358 TI - Excessive Cytolytic Responses Predict Tuberculosis Relapse After Apparently Successful Treatment. AB - BACKGROUND: Currently, there are no tools to accurately predict tuberculosis relapse. This study aimed to determine whether patients who experience tuberculosis relapse have different immune responses to mycobacteria in vitro than patients who remain cured for 2 years. METHODS: Patients with an initial episode of pulmonary tuberculosis were recruited in South Africa. Diluted blood, collected at diagnosis and after 2 and 4 weeks of treatment, was cultured with live Mycobacterium tuberculosis for 6 days, and cellular RNA was frozen. Gene expression in samples from 10 patients who subsequently experienced relapse, confirmed by strain genotyping, was compared to that in samples from patients who remained cured, using microarrays. RESULTS: At diagnosis, expression of 668 genes was significantly different in samples from patients who experienced relapse, compared with expression in patients who remained successfully cured; these differences persisted for at least 4 weeks. Gene ontology and biological pathways analyses revealed significant upregulation of genes involved in cytotoxic cell mediated killing. Results were confirmed by real-time quantitative reverse transcription polymerase chain reaction analysis in a wider patient cohort. CONCLUSIONS: These data show that patients who will subsequently experience relapse exhibit altered immune responses, including excessively robust cytolytic responses to M. tuberculosis in vitro, at the time of diagnosis, compared with patients who will achieve durable cure. Together with microbiological and clinical indices, these differences could be exploited in drug development. PMID- 26351359 TI - Mediators of the Age Effect in the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST). AB - BACKGROUND AND PURPOSE: There is higher combined risk of stroke or death (S+D) at older ages with carotid stenting. We assess whether this can be attributed to patient or arterial characteristics that are in the pathway between older age and higher risk. METHODS: Mediation analysis of selected patient (hypertension, diabetes mellitus, and dyslipidemia) and arterial characteristics assessed at the clinical sites and the core laboratory (plaque length, eccentric plaque, ulcerated plaque, percent stenosis, peak systolic velocity, and location) was performed in 1123 carotid artery stenting-treated patients in the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST). We assessed the association of age with these characteristics, the association of these characteristics with stroke risk, and the amount of mediation of the association of age on the combined risk of periprocedural S+D with adjustment for these factors. RESULTS: Only plaque length as measured at the sites increased with age, was associated with increased S+D risk and significantly mediated the association of age on S+D risk. However, adjustment for plaque length attenuated the increased risk per 10 years of age from 1.72 (95% confidence interval, 1.26-2.37) to 1.66 (95% confidence interval, 1.20-2.29), accounting for only 8% of the increased risk. CONCLUSIONS: Plaque length seems to be in the pathway between older age and higher risk of S+D among carotid artery stenting-treated patients, but it mediated only 8% of the age effect excess risk of carotid artery stenting in CREST. Other factors and mechanisms underlying the age effect need to be identified as plaque length will not identify elderly patients for whom stenting is safe relative to endarterectomy. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00004732. PMID- 26351360 TI - Mouse Models of Cerebral Arteriovenous Malformation. PMID- 26351361 TI - Nursing Assessment of Depression in Stroke Survivors. PMID- 26351362 TI - Imaging Inflammation in Cerebrovascular Disease. AB - Imaging inflammation in large intracranial artery pathology may play an important role in the diagnosis of and risk stratification for a variety of cerebrovascular diseases. Looking beyond the lumen has already generated widespread excitement in the stroke community, and the potential to unveil molecular processes in the vessel wall is a natural evolution to develop a more comprehensive understanding of the pathogenesis of diseases, such as ICAD and brain aneurysms. PMID- 26351363 TI - Analysis of vitamin E metabolites including carboxychromanols and sulfated derivatives using LC/MS/MS. AB - Tocopherols and tocotrienols are metabolized via hydroxylation and oxidation of their hydrophobic side chain to generate 13'-hydroxychromanols (13'-OHs) and various carboxychromanols, which can be further metabolized by conjugation including sulfation. Recent studies indicate that long-chain carboxychromanols, especially 13'-carboxychromanol (13'-COOH), appear to be more bioactive than tocopherols in anti-inflammatory and anticancer actions. To understand the potential contribution of metabolites to vitamin E-mediated effects, an accurate assay is needed to evaluate bioavailability of these metabolites. Here we describe an LC/MS/MS assay for quantifying vitamin E metabolites using negative polarity ESI. This assay includes a reliable sample extraction procedure with efficacy of >= 89% and interday/intraday variation of 3-11% for major metabolites. To ensure accurate quantification, short-chain, long-chain, and sulfated carboxychromanols are included as external/internal standards. Using this assay, we observed that sulfated carboxychromanols are the primary metabolites in the plasma of rodents fed with gamma-tocopherol or delta tocopherol. Although plasma levels of 13'-COOHs and 13'-OHs are low, high concentrations of these compounds are found in feces. Our study demonstrates an LC/MS/MS assay for quantitation of sulfated and unconjugated vitamin E metabolites, and this assay will be useful for evaluating the role of these metabolites in vivo. PMID- 26351364 TI - Xanthine-based KMUP-1 improves HDL via PPARgamma/SR-B1, LDL via LDLRs, and HSL via PKA/PKG for hepatic fat loss. AB - The phosphodiesterase inhibitor (PDEI)/eNOS enhancer KMUP-1, targeting G-protein coupled receptors (GPCRs), improves dyslipidemia. We compared its lipid-lowering effects with simvastatin and explored hormone-sensitive lipase (HSL) translocation in hepatic fat loss. KMUP-1 HCl (1, 2.5, and 5 mg/kg/day) and simvastatin (5 mg/kg/day) were administered in C57BL/6J male mice fed a high-fat diet (HFD) by gavage for 8 weeks. KMUP-1 inhibited HFD-induced plasma/liver TG, total cholesterol, and LDL; increased HDL/3-hydroxy-3-methylglutaryl-CoA reductase (HMGR)/Rho kinase II (ROCK II)/PPARgamma/ABCA1; and decreased liver and body weight. KMUP-1 HCl in drinking water (2.5 mg/200 ml tap water) for 1-14 or 8 14 weeks decreased HFD-induced liver and body weight and scavenger receptor class B type I expression and increased protein kinase A (PKA)/PKG/LDLRs/HSL expression and immunoreactivity. In HepG2 cells incubated with serum or exogenous mevalonate, KMUP-1 (10(-7)~10(-5) M) reversed HMGR expression by feedback regulation, colocalized expression of ABCA1/apolipoprotein A I/LXRalpha/PPARgamma, and reduced exogenous geranylgeranyl pyrophosphate/farnesyl pyrophosphate (FPP)-induced RhoA/ROCK II expression. A guanosine 3',5'-cyclic monophosphate (cGMP) antagonist reversed KMUP-1-induced ROCK II reduction, indicating cGMP/eNOS involvement. KMUP-1 inceased PKG and LDLRs surrounded by LDL and restored oxidized LDL-induced PKA expresion. Unlike simvastatin, KMUP-1 could not inhibit (14)C mevalonate formation. KMUP-1 could, but simvastatin could not, decrease ROCK II expression by exogenous FPP/CGPP. KMUP-1 improves HDL via PPARgamma/LXRalpha/ABCA1/Apo-I expression and increases LDLRs/PKA/PKG/HSL expression and immunoreactivity, leading to TG hydrolysis to lower hepatic fat and body weight. PMID- 26351367 TI - Lyme law: targeting best practices. PMID- 26351365 TI - Deoxycholic acid modulates cell death signaling through changes in mitochondrial membrane properties. AB - Cytotoxic bile acids, such as deoxycholic acid (DCA), are responsible for hepatocyte cell death during intrahepatic cholestasis. The mechanisms responsible for this effect are unclear, and recent studies conflict, pointing to either a modulation of plasma membrane structure or mitochondrial-mediated toxicity through perturbation of mitochondrial outer membrane (MOM) properties. We conducted a comprehensive comparative study of the impact of cytotoxic and cytoprotective bile acids on the membrane structure of different cellular compartments. We show that DCA increases the plasma membrane fluidity of hepatocytes to a minor extent, and that this effect is not correlated with the incidence of apoptosis. Additionally, plasma membrane fluidity recovers to normal values over time suggesting the presence of cellular compensatory mechanisms for this perturbation. Colocalization experiments in living cells confirmed the presence of bile acids within mitochondrial membranes. Experiments with active isolated mitochondria revealed that physiologically active concentrations of DCA change MOM order in a concentration- and time-dependent manner, and that these changes preceded the mitochondrial permeability transition. Importantly, these effects are not observed on liposomes mimicking MOM lipid composition, suggesting that DCA apoptotic activity depends on features of mitochondrial membranes that are absent in protein-free mimetic liposomes, such as the double-membrane structure, lipid asymmetry, or mitochondrial protein environment. In contrast, the mechanism of action of cytoprotective bile acids is likely not associated with changes in cellular membrane structure. PMID- 26351368 TI - Carter v. Canada. PMID- 26351369 TI - De-inking and docs. PMID- 26351370 TI - Heart failure guidelines fail. PMID- 26351372 TI - Social and ethical issues in mitochondrial donation. AB - INTRODUCTION OR BACKGROUND: The UK is at the forefront of mitochondrial science and is currently the only country in the world to legalize germ-line technologies involving mitochondrial donation. However, concerns have been raised about genetic modification and the 'slippery slope' to designer babies. SOURCES OF DATA: This review uses academic articles, newspaper reports and public documents. AREAS OF AGREEMENT: Mitochondrial donation offers women with mitochondrial disease an opportunity to have healthy, genetically related children. AREAS OF CONTROVERSY: Key areas of disagreement include safety, the creation of three parent babies, impact on identity, implications for society, definitions of genetic modification and reproductive choice. GROWING POINTS: The UK government legalized the techniques in March 2015. Scientific and medical communities across the world followed the developments with interest. AREAS TIMELY FOR DEVELOPING RESEARCH: It is expected that the first cohort of 'three parent' babies will be born in the UK in 2016. Their health and progress will be closely monitored. PMID- 26351373 TI - US counties with higher rates of breast cancer screening have higher rates of incidence with no concomitant decrease in breast cancer mortality suggesting overdiagnosis. PMID- 26351378 TI - Varicella Complicated by Severe Pneumonia and Shock in an Immunosuppressed Crohn's Disease Patient Under Azathioprine and Anti-Tumour Necrosis Factor Alpha. PMID- 26351380 TI - High Anti-Tumour Necrosis Factor Trough Concentrations--Only a Cost Issue or Also Hidden Dangers Ahead? PMID- 26351379 TI - Thiopurine Therapy Reduces the Incidence of Colorectal Neoplasia in Patients with Ulcerative Colitis. Data from the ENEIDA Registry. AB - BACKGROUND AND AIMS: Patients with ulcerative colitis (UC) are at increased risk of developing colorectal cancer (CRC), but recent studies suggest a lower risk than previously reported. The aim was to evaluate the incidence of dysplasia, CRC and related risk factors in UC patients from a Spanish nationwide database. METHODS: All UC patients were identified and retrospectively reviewed. Clinical epidemiological data and the finding of dysplasia and/or CRC were collected. RESULTS: A total of 831 UC patients were included. Twenty-six cases of CRC in 26 patients and 29 cases of high-grade dysplasia (HGD) in 24 patients were found, accounting for 55 diagnoses of advanced neoplasia (AN = CRC and/or HGD) in 45 patients (33% of them within the first 8 years after UC diagnosis). The cumulative risk of AN was 2, 5.3 and 14.7% at 10, 20 and 30 years, respectively. Concomitant primary sclerosing cholangitis (odds ratio [OR] 10.90; 95% confidence interval [CI] 3.75-31.76, p < 0.001), extensive UC (OR 2.10, 95% CI 1.01-4.38, p = 0.048), UC diagnosis at an older age (OR 2.23, 95% CI 1.03-4.83, p = 0.043) and appendectomy prior to UC diagnosis (OR 2.66, 95% CI 1.06-6.71, p = 0.038) were independent risk factors for AN. Use of thiopurines (OR 0.21, 95% CI 0.06-0.74, p = 0.015) and being in a surveillance colonoscopy programme (OR 0.33; 95% CI 0.16 0.67; p = 0.002) were independent protective factors for AN. CONCLUSIONS: The risk of AN among UC patients is lower than previously reported but steadily increases from the time of UC diagnosis. The widespread use of thiopurines may have influenced this reduced incidence of UC-related neoplasias. PMID- 26351381 TI - Serum Neutrophil Gelatinase B-associated Lipocalin and Matrix Metalloproteinase-9 Complex as a Surrogate Marker for Mucosal Healing in Patients with Crohn's Disease. AB - BACKGROUND AND AIMS: Although costly and uncomfortable for the patient, the current standard to assess mucosal healing in Crohn's disease [CD] patients is endoscopy. The aim of this study was to evaluate NGAL-MMP-9 as surrogate marker for mucosal healing in CD patients. METHODS: Serum NGAL-MMP-9 levels were determined with sandwich enzyme-linked immunosorbent assay before and up to 5 years after first infliximab infusion in 108 active CD patients [median age at first infliximab 36 years, 57% female] and 43 healthy controls [HC, median age 27 years, 60% female]. Serum samples were matched to the time of endoscopy and complete endoscopic healing was defined as absence of ulcerations. Histological healing was defined as absence of epithelial damage [D'Haens score]. RESULTS: At baseline, median [interquartile range] NGAL-MMP-9 levels were significantly higher in active CD patients vs HC (77.6 [36.9-141.0] vs 25.5 [17.8-42.8] ng/ml; p < 0.001). After treatment, NGAL-MMP-9 levels significantly decreased in completely healed CD patients [n = 38] (84.5 [36.7-138.4] to 23.4 [7.4-42.5] ng/ml; p < 0.001) and--to a lesser extent--in non-healed CD patients [n = 36] (100.9 [43.4-152.6] to 43.8 [27.0-96.8] ng/ml; p = 0.001). Receiver operating characteristic analysis defined a NGAL-MMP-9 cut-off level of 45 ng/ml corresponding to complete endoscopic healing (area under the curve [AUC] = 0.79, 82% sensitivity, 65% specificity) and histological healing [AUC = 0.72, 79% sensitivity, 53% specificity]. At baseline, C-reactive protein [CRP] was not elevated in 33% of active CD patients, whereas 53% of these patients did have elevated NGAL-MMP-9 levels. CONCLUSIONS: In the search for surrogate markers to assess mucosal healing in inflammatory bowel disease, NGAL-MMP-9 supplements and outperforms CRP in both ulcerative colitis and CD patients. PMID- 26351382 TI - Herpes Simplex Virus Sepsis in a Young Woman with Crohn's Disease. AB - We present the case of a herpes simplex virus-1 [HSV-1] sepsis with severe herpes hepatitis in a young female treated with triple immunosuppressive therapy [adalimumab, azathioprine, prednisolone] for refractory Crohn's disease [CD]. The patient presented with high fever, generalised abdominal tenderness, strongly elevated transaminases, coagulopathy, and pancytopenia. Comprehensive diagnostics including blood HSV-1 polymerase chain reaction [PCR], liver biopsy, and immunohistochemistry revealed the diagnosis of fulminant herpes hepatitis. HSV-1 positivity of cutaneous lesions proved the disseminated nature of the infection. Early treatment with intravenous acyclovir led to a rapid improvement of the patient's condition and resulted in a full recovery of her liver function. This is the first reported case of HSV-sepsis in a patient with CD. Physicians treating inflammatory bowel disease [IBD] patients with combined immunosuppressive therapy should be aware of the possibility of herpes hepatitis, and early empirical antiviral therapy should be considered in immunosuppressed patients presenting with fever and severe anicteric hepatitis. PMID- 26351383 TI - Endoscopic Factors Influencing Fecal Calprotectin Value in Crohn's Disease. AB - BACKGROUND AND AIMS: Fecal calprotectin [fcal] is a biomarker of Crohn's disease [CD] endoscopic activity. Identifying the endoscopic situations in which fcal is less reliable remains unexplored. We aimed to determine the endoscopic factors influencing fcal level in CD. METHODS: Overall, 53 CD patients consecutively and prospectively underwent colonoscopy, with CD Endoscopic Index of Severity [CDEIS] calculation and stool collection. Fcal was measured using a quantitative immunochromatographic test. Correlation analysis was done with Pearson statistics. RESULTS: Fcal was correlated with CDEIS [0.66, p < 0.001]. In univariate analysis, fcal was correlated with the affected surface [0.65, p < 0.001] and the ulcerated surface [0.47, p < 0.001]. Fcal was significantly associated with ulceration depth, with median fcal of 867.5 ug/g, 1251.0 ug/g, and 1800.0 ug/g, in patients presenting with non-ulcerated lesions, superficial ulcerations [SU], and deep ulcerations [DU], respectively. Lesion locations did not influence fcal. In multivariate analysis, fcal was associated with affected surface [p = 0.04] and the presence of CD lesions. Moreover, fcal increased with the ulceration depth [p = 0.03]. However, ulcerated surface and CD location did not affect fcal. Using a receiver operating characteristic [ROC] curve, we showed that fcal of 400 ug/g was the best compromise between sensitivity [0.76] and specificity [0.77], whereas fcal >= 200 ug/g was highly sensitive [0.86] to detect SU or DU. CONCLUSIONS: Fcal is a very reliable biomarker to detect endoscopic ulcerations in CD. We suggest repeating measurement in case of intermediary results [200-400 ug/g] in daily practice. Fcal level is mostly influenced by the presence of CD lesions [even non-ulcerated], in a depth-related manner and by the affected surface. PMID- 26351384 TI - Inflammatory Bowel Disease and Pancreatitis: A Review. AB - BACKGROUND AND AIMS: Pancreatic abnormalities are common in inflammatory bowel disease (IBD) patients and represent a heterogeneous group of conditions that include acute pancreatitis, chronic pancreatitis, autoimmune pancreatitis and asymptomatic abnormalities. We sought to review the available evidence concerning the aetiology, clinical presentation, diagnosis and treatment of pancreatic conditions in IBD patients. METHODS: A PubMed/Medline query was conducted addressing pancreatic disorders in IBD. Reference lists from studies selected were manually searched to identify further relevant reports. Relevant manuscripts about pancreatic disorders in patients with IBD were selected and reviewed. RESULTS: Thiopurines and gallstones are the most frequent causes of acute pancreatitis in IBD patients. Thiopurine-induced acute pancreatitis is usually uncomplicated and self-limited. Some evidence suggests that chronic pancreatitis may be more common in IBD. Most cases are idiopathic, affecting young males and patients with ulcerative colitis. Autoimmune pancreatitis is a relatively newly recognized disease and is increasingly diagnosed in IBD, particularly for type 2 autoimmune pancreatitis in ulcerative colitis patients. Asymptomatic exocrine insufficiency, pancreatic duct abnormalities and hyperamylasaemia have been identified in up to 18% of IBD patients, although their clinical significance and relationship with IBD remain undefined. CONCLUSIONS: The wide spectrum of pancreatic manifestations in IBD is growing and may represent a challenge to the clinician. A collaborative approach with a pancreas specialist may be the most productive route to determine aetiology, guide additional diagnostic workup, illuminate the aetiology and define the treatment and follow-up of these patients. PMID- 26351385 TI - Do Thiopurines Really Decrease the Risk of Colorectal Cancer in Ulcerative Colitis? The Light is Coming from Concept-based Subgroup Analyses. PMID- 26351386 TI - A Matrix-based Model Predicts Primary Response to Infliximab in Crohn's Disease. AB - BACKGROUND: Prediction of primary non-response [PNR] to anti-tumour necrosis factors [TNFs] in inflammatory bowel disease [IBD] is direly needed to select the optimal therapeutic class for a given patient. We developed a matrix-based prediction tool to predict response to infliximab [IFX] in Crohn's disease [CD] patients. METHODS: This retrospective single-centre study included 201 anti-TNF naive CD patients who started with IFX induction therapy. PNR occurred in 16 [8%] patients. Clinical, biological [including serum TNF and the IBD serology 6 panel and genetic [the 163 validated IBD risk loci] markers were collected before start. Based on the best fitted regression model, probabilities of primary response to IFX were calculated and arranged in a prediction matrix tool. RESULTS: Multiple logistic regression withheld three final independent predictors [p < 0.05] for PNR: age at first IFX, {odds ratio (OR) (95% confidence interval [CI] of 1.1 (1.0-1.1)}, body mass index [BMI] (0.86 [0.7-1.0]), and previous surgery (4.4 [1.2-16.5]). The accuracy of this prediction model did not improve when the genetic markers were added (area under the curve [AUC] from 0.80 [0.67 0.93] to 0.78 [0.65-0.91]). The predicted probabilities for PNR to IFX increased from 1% to 53% depending on the combination of final predictors. CONCLUSIONS: Readily available clinical factors [age at first IFX, BMI, and previous surgery] outperform serological and IBD risk loci in prediction of primary response to infliximab in this real-life cohort of CD patients. This matrix tool could be useful for guiding physicians and may avoid unnecessary or inappropriate exposure to IFX in IBD patients unlikely to benefit. PMID- 26351387 TI - Keratoconus in Inflammatory Bowel Disease Patients: A Cross-sectional Study. AB - BACKGROUND AND AIMS: Increasing evidence suggests that keratoconus may have an inflammatory component. The possible association of keratoconus with inflammatory bowel disease (IBD) has yet to be determined. The aim of this study was to determine the prevalence of keratoconus and suspect keratoconus in patients with IBD. METHODS: All consecutive adult IBD patients seen in the Department of Gastroenterology, Nancy, University Hospital, France, between March 2014 and June 2014 were included. Pregnant women, rigid lens wearers, patients with a family history of keratoconus and patients with a history of refractive surgery were excluded. A control group of healthy subjects was included. All included patients underwent a corneal topography (OPD-Scan III, Nidek) to detect keratoconus or suspect keratoconus. Rabinowitz videokeratographic indices were the basis of corneal topography interpretation. RESULTS: Two hundred and one IBD patients were included, 150 with Crohn's disease and 51 with ulcerative colitis. Mean age was 38.7 years and 121 were women. Mean disease duration was 10.8 years. Two IBD patients were diagnosed with keratoconus (1%) and 38 with suspect keratoconus (18.9%). Overall prevalence of keratoconus and suspect keratoconus was 19.9% (95% confidence interval [CI] 17.5-22.0). None of the 100 healthy subjects had keratoconus, while three were diagnosed with suspect keratoconus (p = 0.0002 versus IBD patients). Only smoking was identified as a risk factor (p = 0.029), especially in Crohn's disease. CONCLUSION: Inflammatory bowel disease patients may carry an increased risk of keratoconus and suspect keratoconus, smoking further increasing this risk. This supports the hypothesis of an inflammatory origin of keratoconus. PMID- 26351388 TI - Association Between Infliximab Trough Levels and the Occurrence of Paradoxical Manifestations in Patients with Inflammatory Bowel Disease: a Case-Control Study. AB - BACKGROUND AND AIM: Anti-tumour necrosis factor [TNF] agents have dramatically improved the prognosis of inflammatory bowel disease [IBD]. However, despite their good safety profile, use of these agents may lead to paradoxical manifestations involving skin or joints. Pathogenesis of such side effects is poorly understood and may involve anti-TNF pharmacokinetics. The aim of the present study was to look for an association between infliximab trough levels [ITL] and cutaneous [CPM] or rheumatological [RPM] paradoxical manifestations. METHODS: IBD patients receiving infliximab as maintenance therapy were included in a cross-sectional prospective monocentre study. At inclusion, patients had an ITL measurement [LISA-TRACKER(r), Biomedical Diagnostics BMD] and were assessed for paradoxical manifestations: a CPM was defined by new onset or exacerbation of pre-existing psoriasis lesions during IFX therapy, and an RPM by new onset of severe poly-arthralgia during IFX therapy. RESULTS: Among the 121 patients included [69 female; median age: 38.9 years; 92 with Crohn's disease], 7% had CPM and 8% RPM. Median ITL values were 5.87 [range: 0.52-19.53] ug/ml in patients with CPM and 1.90 [0.00-13.5] ug/ml in those with RPM, as compared respectively with 5.12 [0.00-49.12] ug/ml in patients without CPM [p = 0.56] and 5.57 [0.00 49.12] ug/ml in those without RPM [p = 0.058]. No prognostic factor was associated with CPM. The single factor associated with RPM was elevated antinuclear antibodies. CONCLUSION: ITL were not elevated in IBD patients developing cutaneous or rheumatological paradoxical manifestations when receiving IFX as maintenance therapy. As suggested by the high level of antinuclear antibodies, RPM could be related to an induced autoimmune disorder. PMID- 26351389 TI - Postoperative Inflammatory Response in Crohn's Patients: A Comparative Study. AB - BACKGROUND AND AIMS: Surgery for Crohn's disease [CD] can be complicated by an enhanced inflammatory response. This retrospective study aims to compare the inflammatory response measured by C-reactive protein [CRP] in patients operated for CD with patients undergoing similar surgery for colorectal cancer [CRC]. METHODS: All CD patients undergoing an ileocaecal resection between February 2001 and December 2013 were retrieved from a prospectively maintained database. The same number of patients with a CRC of the ascending colon, undergoing a laparoscopic right hemicolectomy between March 2009 and June 2014, were retrieved from a CRC database. CRP level during the first 7 postoperative days was used as primary outcome. RESULTS: Totals of 112 consecutive CD patients (male 40.2%; median age: 32.3 yrs; interquartile range [IQR]: 25.2-45.1) and 112 consecutive CRC patients [male 53.6%; median age 71.6 yrs; IQR: 64.7-77.5] were included. Postoperative CRP level in the CD group was on average 27% higher compared with the CRC group [p = 0.02]. The day-specific differences in CRP values were 21% (p = 0.021, 95% confidence interval [CI]: 3% 41%), 41% [p = 0.005, 95% CI: 11%-79%], 49% [p = 0.007, 95% CI: 11%-96%], and 49% [p = 0.006, 95% CI: 12%-100%] higher for CD patients at Days 1, 4, 5, and 6 respectively. The difference in postoperative CRP level was partially due to differences in preoperative CRP level. CONCLUSION: CD patients develop a higher postoperative CRP level, probably reflecting an enhanced postoperative inflammatory response, which may be triggered by a higher preoperative inflammatory state. PMID- 26351390 TI - Evaluation of the Risk of Relapse in Ulcerative Colitis According to the Degree of Mucosal Healing (Mayo 0 vs 1): A Longitudinal Cohort Study. AB - BACKGROUND AND AIMS: Mucosal healing in ulcerative colitis (UC) has become a common endpoint in most clinical trials and a relevant therapeutic goal in clinical practice. Despite important differences between endoscopic Mayo scores 0 and 1, both scores are considered as mucosal healing in most important trials. The aim of the present study was to evaluate the risk of relapse in UC patients according to the degree of mucosal healing (endoscopic Mayo scores of 0 and 1). METHODS: A prospective longitudinal cohort study was designed. All UC patients who presented with mucosal healing at colonoscopy were consecutively included. Mucosal healing was defined as an endoscopic Mayo score of 0 or 1. Clinical relapse was defined as the need for therapy to induce remission, any treatment escalation, hospitalization or colectomy. All clinical relapses were evaluated at months 6 and 12 after study entry. Results were subjected to unconditional stepwise logistic and Kaplan-Meier regression analysis. RESULTS: One hundred and eighty-seven consecutive UC patients (126 [67.3%] with Mayo score 0 and 61 [32.7%] with Mayo score 1) were included. Of patients with Mayo scores 0 and 1, 9.4 and 36.6% respectively presented a relapse during the first 6 months of follow-up (p < 0.001). The only factor independently associated with UC relapses in the multivariate analysis was an endoscopic Mayo score of 1 (odds ratio 6.27, 95% confidence interval 2.73-14.40, p < 0.001). CONCLUSIONS: Patients with an endoscopic Mayo score of 1 have a higher risk of relapse than those with a score of 0. The concept of mucosal healing should be limited to patients with an endoscopic Mayo score of 0. PMID- 26351391 TI - Altered Fecal Microbiota in Paediatric Inflammatory Bowel Disease. AB - BACKGROUND AND AIMS: Several factors support the view of inflammatory bowel disease [IBD] origin in the host responsiveness to intestinal bacteria, although no single bacterial species has been shown as a causative agent in the pathogenesis. Our aim was to analyse the fecal microbiota of paediatric IBD patients at different stages of the disease. In addition, the characteristics of immune response to the bacterial isolates showing very low abundance in IBD were studied. METHODS: Fecal samples [1-3 samples/child] were collected from 10 paediatric patients with crohn's disease [CD], and 12 with ulcerative colitis [UC] and from 8 healthy children, for polyphasic microbiological analysis (culture, real-time polymerase chain reaction [PCR], and denaturing gradient gel electrophoresis). In addition, in vitro cytokine responses of peripheral blood mononuclear cells to the bacterial isolates, which showed very low abundance in IBD, were studied. RESULTS: Although predominant bacterial diversity was higher in IBD, the numbers of Lachnospiraceae and Coriobacteriaceae bacteria were lower in IBD patients as compared with control children [p < 0.05]. In addition, Ruminococcaceae population diversity was lower in IBD [p < 0.05] and correlated negatively with fecal calprotectin levels. Both abundance and diversity of bifidobacterial populations were lower in children with IBD [p < 0.05], and particularly low numbers of certain bifidobacterial isolates were detected. In CD, we found enhanced up-regulation of interleukin-6 transcripts and impaired RAR related orphan receptor C response to bifidobacteria, whereas decreased interferon-gamma response was observed in both CD and UC. CONCLUSION: We demonstrate altered fecal microbiota in paediatric IBD, particularly low numbers and diversity of bifidobacterial populations. Interestingly, immunological response to bifidobacteria differed between paediatric CD patients and control children. PMID- 26351394 TI - Intracoronary imaging: see more, better or worse? PMID- 26351393 TI - Fistula Plug in Fistulising Ano-Perineal Crohn's Disease: a Randomised Controlled Trial. AB - BACKGROUND AND AIMS: Anal fistula plug [AFP] is a bioabsorbable bioprosthesis used in ano-perineal fistula treatment. We aimed to assess efficacy and safety of AFP in fistulising ano-perineal Crohn's disease [FAP-CD]. METHODS: In a multicentre, open-label, randomised controlled trial we compared seton removal alone [control group] with AFP insertion [AFP group] in 106 Crohn's disease patients with non- or mildly active disease having at least one ano-perineal fistula tract drained for more than 1 month. Patients with abscess [collection >= 3mm on magnetic resonance imaging or recto-vaginal fistulas were excluded. Randomisation was stratified in simple or complex fistulas according to AGA classification. Primary end point was fistula closure at Week 12. RESULTS: In all, 54 patients were randomised to AFP group [control group 52]. Median fistula duration was 23 [10-53] months. Median Crohn's Disease Activity Index at baseline was 81 [45-135]. Fistula closure at Week 12 was achieved in 31.5% patients in the AFP group and in 23.1 % in the control group (relative risk [RR] stratified on AGA classification: 1.31; 95% confidence interval: 0.59-4.02; p = 0.19). No interaction in treatment effect with complexity stratum was found; 33.3% of patients with complex fistula and 30.8% of patients with simple fistula closed the tracts after AFP, as compared with 15.4% and 25.6% in controls, respectively [RR of success = 2.17 in complex fistula vs RR = 1.20 in simple fistula; p = 0.45]. Concerning safety, at Week 12, 17 patients developed at least one adverse event in the AFP group vs 8 in the controls [p = 0.07]. CONCLUSION: AFP is not more effective than seton removal alone to achieve FAP-CD closure. PMID- 26351392 TI - Immunogenicity and Safety of Influenza Vaccine in Inflammatory Bowel Disease Patients Treated or not with Immunomodulators and/or Biologics: A Two-year Prospective Study. AB - BACKGROUND AND AIMS: Data on the efficacy and safety of seasonal influenza vaccines in patients with inflammatory bowel disease (IBD) remain scarce. The aim of the study was to evaluate the impact of immunosuppressive (IS) therapeutics on serological response to 2-year influenza vaccination in IBD adults. METHODS: A multicentre prospective study performed in 255 IBD adults (18-64 years) receiving the trivalent influenza vaccine in the years 2009-2010 and 2010-2011. Haemagglutination inhibition (HI) titres were assessed before and 3 weeks and 6 months after vaccination. RESULTS: At inclusion, 31 patients were receiving no IS treatment (Group A), 77 were receiving IS treatment without anti-TNF (Group B) and 117 were receiving anti-tumour necrosis factor (TNF) treatment with or without IS treatment (Group C). Three weeks after the first vaccination, rates of seroprotection were 77, 75 and 66% for strain A/H1N12007 (p = 0.35), 77, 68 and 52% for strain A/H3N2 (p = 0.014) and 97, 96 and 95% for strain B (p = 0.99) in Groups A, B and C, respectively. Seroconversion rates for A/H1N12007 (67, 64 and 54%; p = 0.28), A/H3N2 (63, 50 and 41%; p = 0.074) and strain B (63, 76 and 60%; p = 0.078) were not significantly different among treatment groups. At 6 months after vaccination, seroprotection rates were lower in Group C compared with Groups A and B. Comparable results were observed for the second year of vaccination. No impact on Harvey-Bradshaw and Mayo scores was detected. CONCLUSIONS: Influenza vaccine yielded high seroprotection rates in IBD patients. Persistence of seroprotection was lower in patients with anti-TNF treatment. ClinicalTrials.gov, number NCT01022749. PMID- 26351396 TI - A new shield from the double-edged sword of reperfusion in STEMI. PMID- 26351395 TI - Innate immune cells in ischaemic heart disease: does myocardial infarction beget myocardial infarction? AB - Knowledge of macrophages in steady-state and diseased tissue is rapidly expanding, propelled by improved diagnostic capacity to detect and monitor cells in their native environments. In this review, we discuss implications for ischaemic heart disease and examine innate immune cell pathways that increase systemic leucocyte supply after myocardial infarction (MI). Acute MI alters the macrophage phenotype and supply chain from tissue resident to blood monocytes sourced from haematopoietic organs. That blood leucocytosis closely associates with cardiovascular mortality provides a strong motivation to understand why and how organ ischaemia alters cellular immunity. PMID- 26351397 TI - Assessing bleeding risk in atrial fibrillation with the HAS-BLED and ORBIT scores: clinical application requires focus on the reversible bleeding risk factors. PMID- 26351398 TI - Which animal model is proper for evaluation of a muscular ventricular septal defect closure device? PMID- 26351399 TI - Reply to Son et al. PMID- 26351400 TI - Double row of overlapping sutures for downsizing annuloplasty decreases the risk of residual regurgitation in ischaemic mitral valve repair. AB - OBJECTIVES: The aim of this study was to evaluate a novel insertion technique of the prosthetic ring that would further magnify the degree of annulus narrowing, thereby reducing the potential for a residual leak in ischaemic mitral valve repair. METHODS: Thirty-six patients with ischaemic mitral regurgitation (MR) were randomly assigned into two groups. In 18 patients, the prosthetic ring was inserted in the conventional manner with a single row of sutures (control group). In the remaining 18 patients, the ring was attached using a double row of sutures tied both on the inner and on the outer part of the sewing cuff. Both groups had similar preoperative clinical and echocardiographic characteristics with severe leaflet tethering: mean tenting area >2.5 cm(2), mean anterior leaflet angle >25 degrees and posterior leaflet angle >45 degrees . The mean prosthetic ring sizes inserted in both groups were identical (mean: 27.3 mm). RESULTS: At 12 months, there was no clinical event except for 1 rehospitalization in the control group. The mean mitral regurgitation grade was higher in the control group than in the group with the double row of sutures at 1.6 +/- 0.9 vs 0.7 +/- 0.3 (P = 0.0003). Annulus diameter reduction was less pronounced in the control group when compared with the group with the double row of sutures, both in the parasternal long-axis: 29.3 +/- 3 vs 26.3 +/- 3 mm (P = 0.0003) and in apical four-chamber views: 31 +/- 3 vs 28 +/- 2 mm (P = 0.003). Leaflet tethering indices were greater in the control group than in the group with the double row of sutures: tenting area: 1.42 +/- 0.3 vs 1.1 +/- 0.5 cm(2) (P = 0.002), anterior leaflet angle: 33 +/- 3 degrees vs 28 +/- 5 degrees (P = 0.0009) and posterior leaflet angle: 110 +/- 13 degrees vs 80 +/- 11 degrees (P = 0.0001). Left ventricular function parameters were not statistically different among the two groups. CONCLUSION: A double row of overlapping sutures for attaching the prosthetic ring in downsizing annuloplasty is more efficient in narrowing the mitral annulus than the conventional technique in ischaemic mitral repair. Even in high-risk patients whose leaflets were severely tethered on echocardiography, it almost eliminated the risk of MR recurrence in this study. PMID- 26351401 TI - Eight years of the EACVI's grant programme: existing developments, impact, and steps forward. PMID- 26351402 TI - News Feature: Secret life. PMID- 26351404 TI - Prognostic Role of MicroRNA-126 for Survival in Malignant Tumors: A Systematic Review and Meta-Analysis. AB - BACKGROUND: Increasing studies found that miR-126 expression may be associated with the prognosis of cancers. Here, we performed a meta-analysis to assess the prognostic role of miR-126 in different cancers. METHODS: Eligible studies were identified by searching in PubMed, Embase, the Cochrane Library, CNKI, and Wan Fang databases up to March 2015. Pooled hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) were calculated to investigate the correlation between miR-126 and survival of cancers. RESULTS: Thirty studies including a total of 4497 participants were enrolled in this meta-analysis. The pooled results showed that high level of miR-126 was a predictor for favorable survival of carcinomas, with pooled HR of 0.77 (95% CI 0.64-0.93) for OS, 0.64 (95%CI 0.48-0.85) for DFS, and 0.70 (95% CI 0.50-0.98) for PFS/RFS/DSS. However, high level of circulating miR-126 predicted a significantly worse OS in patients with cancer (HR = 1.65, 95% CI 1.09-2.51). CONCLUSIONS: Our results indicated that miR-126 could act as a significant biomarker in the prognosis of various cancers. PMID- 26351405 TI - Feasibility of Comparing the Results of Pancreatic Resections between Surgeons: A Systematic Review and Meta-Analysis of Pancreatic Resections. AB - Background. Indicators of operative outcomes could be used to identify underperforming surgeons for support and training. The feasibility of identifying HPB surgeons with poor operative performance ("outliers") based on the results of pancreatic resections is not known. Methods. A systematic review of Medline, Embase, and the Cochrane library was performed to identify studies on pancreatic resection including at least 100 patients and published between 2004 and 2014. Proportions that lay outside the upper 95% and 99.8% confidence intervals based on results of the systematic reviews were considered as "outliers." Results. In total, 30 studies reporting on 10712 patients were eligible for inclusion in this review. The average short-term mortality after pancreatic resections was 3.1% and proportion of patients with procedure-related complications was 47.0%. None of the classification systems assessed the long-term impact of the complications on patients. The surgeon-specific mortality should be 5 times the average mortality before he or she can be identified as an outlier with 0.1% false positive rate if he or she performs 50 surgeries a year. Conclusions. A valid risk prognostic model and a classification system of surgical complications are necessary before meaningful comparisons of the operative performance between pancreatic surgeons can be made. PMID- 26351406 TI - Qualitative Characteristics of Depression in Parkinson's Patients and Controls. AB - BACKGROUND: Depression is common in Parkinson's disease (PD); in light of typical PD pathology it may differ phenomenologically from depression in the general population. OBJECTIVE: To assess depressive symptoms in PD patients and control groups and compare symptom profiles. METHODS: After postal screening of 10,000 citizens of Lubeck, 642 participants were examined and the Beck Depression Inventory (BDI) was sufficiently answered by 477 subjects. Based on motor examinations, we distinguished PD patients, Healthy Controls (HC, no motor impairment), and Disease Controls (DC, motor impairment other than PD). RESULTS: The sample comprised 331 men and 311 women, aged 65 +/- 8 years. Out of the overall sample, 198 (41.5%) had a BDI score >=9. BDI results above 9 points occurred in 34.5% of HC, 50.3% of DC, and 42.4% of PD patients. Compared to the control groups (HC, DC) the PD patients endorsed more "dissatisfaction" and "loss of appetite" but less "feelings of guilt," "self-hate," and "loss of libido." CONCLUSION: Depressive symptoms are more frequent in PD patients compared to HC but not DC. Interestingly, the distribution of individual symptoms of the BDI differs between groups with an emphasis on loss of pleasure/enjoyment in the PD group, a symptom typically considered to be dopaminergically transmitted. PMID- 26351407 TI - Synthesis and Validation of a Hydroxypyrone-Based, Potent, and Specific Matrix Metalloproteinase-12 Inhibitor with Anti-Inflammatory Activity In Vitro and In Vivo. AB - A hydroxypyrone-based matrix metalloproteinase (MMP) inhibitor was synthesized and assayed for its inhibitory capacity towards a panel of ten different MMPs. The compound exhibited selective inhibition towards MMP-12. The effects of inhibition of MMP-12 on endotoxemia and inflammation-induced blood-cerebrospinal fluid barrier (BCSFB) disruption were assessed both in vitro and in vivo. Similar to MMP-12 deficient mice, inhibitor-treated mice displayed significantly lower lipopolysaccharide- (LPS-) induced lethality compared to vehicle treated controls. Following LPS injection Mmp-12 mRNA expression was massively upregulated in choroid plexus tissue and a concomitant increase in BCSFB permeability was observed, which was restricted in inhibitor-treated mice. Moreover, an LPS-induced decrease in tight junction permeability of primary choroid plexus epithelial cells was attenuated by inhibitor application in vitro. Taken together, this hydroxypyrone-based inhibitor is selective towards MMP-12 and displays anti-inflammatory activity in vitro and in vivo. PMID- 26351408 TI - IL-17A, IL-22, IL-6, and IL-21 Serum Levels in Plaque-Type Psoriasis in Brazilian Patients. AB - Psoriasis is a chronic inflammatory skin disease characterized by alterations in cytokines produced by both Th1 and Th17 pathways. The aim of this study was to evaluate serum levels of pivotal cytokines and correlate them with clinical parameters. Serum samples from 53 psoriasis patients and 35 healthy volunteers, matched by the proportion of sex and age ratios, were collected for ELISA cytokine detection. Psoriasis Area and Severity Index (PASI) was assessed at the time of sampling in psoriasis patients. Our findings demonstrate that IL-17A, IL 22, and IL-6 serum concentrations were significantly higher in psoriasis patients than in the control group. No statistical correlation could be found between cytokines concentrations, PASI score, and age in this study. Although our results do not show any correlation between serum levels of IL-17A, IL-22, and IL-6 and disease activity, the present study confirms that they were increased in Brazilian psoriasis patients in comparison to healthy volunteers. PMID- 26351409 TI - Comparison of Neurocognitive Testing and the Measurement of Marinobufagenin in Mild Traumatic Brain Injury: A Preliminary Report. AB - The evaluation of concussed athletes, including testing to determine if and when they may return to play, has become an important task of athletic trainers and team physicians. Currently, concussion protocols are in place, which depend largely upon assessments based upon neurocognitive testing (NCT). The authors have evaluated the use of a biomarker of brain trauma, marinobufagenin (MBG), and compared its application in concussed athletes with the performance of NTC. We found a disparity between these two testing procedures. In this communication, the findings of these comparative data are presented. We noted that athletes whose NCT evaluations had returned to baseline and who were allowed to again participate in play then showed a recurrence of elevated urinary MBG excretion. These observations raise concern as to the processes currently in effect with regard to the decision as to returning athletes to the full activity. They suggest a need for further evaluation. PMID- 26351410 TI - "Partners rather than just providers...": A qualitative study on health care professionals' views on implementation of multidisciplinary group meetings in the North West London Integrated Care Pilot. AB - INTRODUCTION: Multidisciplinary group meetings are one of the key drivers of facilitating integrated care. Health care professionals attending such groups have a key role in the success of these discussions and hence, in the forming of multi-professional integrated care. The study aimed to explore the professionals' experiences and views of participating and implementing the groups in integrated care context. METHODS: A qualitative study including 25 semi-structured interviews with professionals participating in the Northwest London Integrated Care Pilot analysed using thematic content analysis. RESULTS: Participants mentioned a number of benefits of participating in the meetings, including shared learning and shared decision-making between different services and specialties. Yet, they perceived barriers that diminish the efficiency of the groups, such as time constraints, group dynamics and technicalities. The participants felt that the quality of discussions and facilitation could be improved, as well as technical arrangements that would make them easier to participate. Most of the participants perceived the groups to be beneficial for providers mostly questioning the benefits for patient care. CONCLUSION: Findings provide an insight into how health professionals' views of their participation to the multidisciplinary group meetings can be more effectively translated into more tangible benefits to the patients. To benefit patient care, the multidisciplinary groups need to be more patient-oriented rather than provider-oriented, while overcoming professional boundaries for participating. PMID- 26351411 TI - Mixed Adenoneuroendocrine Carcinoma of the Stomach. AB - Mixed adenoneuroendocrine carcinoma is a rare condition comprising at least 30%percnt; of each component of exocrine and endocrine tumors. The denominations were defined in the 2000 WHO classification of endocrine tumors. We report an 83 year-old male with a polypoid gastric tumor in the gastric high body who received total gastrectomy and died 8 months after the diagnosis from local recurrence and distal metastases. A review of the literature for this infrequent condition is presented. PMID- 26351412 TI - T-Cell Lymphomas Presenting as Colon Ulcers and Eosinophilia. AB - Primary gastrointestinal T-cell lymphoma is an uncommon entity and primary colon T-cell lymphoma is even rarer. The majority of enteropathy-associated T-cell lymphomas present predominantly as ulcers or strictures in the endoscopic examinations, while primary B-cell lymphomas commonly present as exophytic lesions. Ulcerative colon T-cell lymphoma may mimic Crohn's disease (CD), which is a chronic inflammatory disease of the intestines with ulcer and fistula formations difficult for clinicians to diagnose based on endoscopic observations alone. Like CD, T-cell lymphoma may be characterized by the presence of multiple skipped ulcers distributed from the terminal ileum to the descending colon. Furthermore, it is difficult to diagnose this unusual lymphoma by a single endoscopic biopsy. Typically, the histological composition of T-cell lymphoma is made of medium to large atypical cells located in the base of the ulcer with extension to the muscle layer and the adjacent mucosa. However, it is common that biopsy specimens show only mixed inflammatory changes where the lymphoma cells are hard to be identified. The differential diagnosis of malignant lymphoma must be considered when clinically diagnosed CD is refractory to the medical treatment or when its clinical behavior becomes aggressive. The current study presents a rare case of primary colon T-cell lymphoma in a 56-year-old male with marked recent weight loss, watery diarrhea and bilateral neck lymphadenopathy, who received a laboratory checkup and endoscopic workup for colon biopsy. The initial pathological report was consistent with mucosal inflammation and benign colon ulcers. Interestingly, the blood test showed a prominent eosinophilia. A biopsy of the enlarged neck lymph nodes done approximately 1 month after the colon biopsy unexpectedly showed T-cell lymphoma, which led to a review of the initial colonic biopsy specimens. Additional immunohistochemical stains were used accordingly, which showed positive results for CD3, CD45RO and LCA antibodies confirming the diagnosis of lymphoma. The endoscopic diagnosis of ulcerative colon T-cell lymphoma is frequently confused with inflammatory conditions of the large bowel such as CD, and tuberculosis colitis. Our study aims to emphasize the difficulty in differentiating this ulcerative form of colon T-cell lymphoma from the inflammatory bowel diseases and the importance of its differential diagnosis due to the much more aggressive clinical behavior of the T-cell lymphoma. PMID- 26351413 TI - Presentation, Diagnosis, and Management of Esophageal Lichen Planus: A Series of Six Cases. AB - Lichen planus (LP) is an idiopathic disorder that presents with cutaneous and genital manifestations. Esophageal LP (ELP) was first described by Al-Shihabi and Jackson [J Laryngol Otol 1982;96:567-571] in 1982. Only approximately 80 cases have been documented in the literature since. It is a rare and underrecognized disorder, leading to a delay in diagnosis and a lack of standardized management. We describe the presentation, diagnosis, and management of 6 cases of ELP, at a tertiary institution, because we believe that an increasing awareness of this condition can help identify more cases and increase our understanding of this interesting condition. PMID- 26351414 TI - Abnormal Liver Function Tests in an Anorexia Nervosa Patient and an Atypical Manifestation of Refeeding Syndrome. AB - Refeeding syndrome is defined as electrolyte and fluid abnormalities that occur in significantly malnourished patients when they are refed orally, enterally, or parenterally. The principal manifestations include hypophosphatemia, hypokalemia, vitamin deficiencies, volume overload and edema. This can affect multiple organ systems, such as the cardiovascular, pulmonary, or neurological systems, secondary to the above-mentioned abnormalities. Rarely, patients may develop gastrointestinal symptoms and show abnormal liver function test results. We report the case of a 52-year-old woman with anorexia nervosa who developed refeeding syndrome and simultaneous elevations of liver function test results, which normalized upon the resolution of the refeeding syndrome. PMID- 26351415 TI - Metastatic Fibrolamellar Hepatocellular Carcinoma to the Pancreas. AB - Fibrolamellar hepatocellular carcinoma (FL-HCC) is a rare variant of hepatocellular carcinoma, usually presenting in the younger population (<40 years) without underlying liver disease. Although it has a better prognosis than hepatocellular carcinoma, it has a high rate of recurrence months to years after primary resection. While sites of recurrence usually involve the liver, regional lymph nodes, peritoneum, and lung, metastasis to the pancreas is extremely rare, with only 2 other cases reported in the literature. We present the case of a 46 year-old patient with metastatic FL-HCC to the pancreas 30 years after diagnosis and 26 years since his last resected liver recurrence. PMID- 26351416 TI - Two Cases of Severe Ulcerative Colitis with Colonic Dilatation Resolved with Tacrolimus Therapy. AB - We report 2 cases of ulcerative colitis (UC) with intestinal tract dilatation treated with tacrolimus. They were 53- and 64-year-old males, who had been admitted to local hospitals for increasing severity of their UC symptoms. Treatment for severe UC was immediately started, but both cases were refractory to corticosteroid therapy; they were then transferred to our hospital. When they were referred to our hospital, they had frequent bloody diarrhea, fever, severe abdominal pain, and even dilatation of the transverse colon on abdominal X-ray test. They were treated with oral tacrolimus medication, and their symptoms improved immediately. Dilatation of the transverse colon was improved on plain X ray at 2 weeks after starting therapy, and emergency colectomy could be avoided. These 2 cases may suggest that tacrolimus is effective for UC with colonic dilatation as a rescue therapy. PMID- 26351417 TI - Metastatic Breast Cancer to the Common Bile Duct Presenting as Obstructive Jaundice. AB - Metastatic breast cancer is typically identified in the bones, lymph nodes, lungs and liver. Rarely does metastatic breast cancer involve the common bile duct (CBD) without direct extension from liver metastasis into the CBD. We present a woman diagnosed with metastatic breast cancer in the CBD after presenting with obstructive jaundice. Patients with a history of primary breast cancer who present with obstructive jaundice secondary to CBD mass need identification of the mass in order to provide appropriate treatment. PMID- 26351418 TI - Long-Term Maintenance of Complete Response after Sorafenib Treatment for Multiple Lung Metastases from Hepatocellular Carcinoma. AB - Sorafenib is an effective treatment for unresectable hepatocellular carcinoma (HCC) characterized by disease stabilization. However, the response rates are very low (<9%percnt;), and a complete response is rarely achieved. We report an extremely rare case of a HCC patient with multiple lung metastases treated with sorafenib who achieved a complete response for a long period. A 77-year-old woman was diagnosed with chronic hepatitis C in 1990. In 2007, a HCC detected in the liver was treated with percutaneous ethanol injection therapy. Subsequently, recurrence of HCC in the liver was treated with microwave coagulonecrotic therapy in 2010. In April 2011, a computed tomography (CT) scan revealed innumerable multiple metastases spread diffusely in both lungs. Tumor marker levels were extremely high [alpha-fetoprotein (AFP) 76,170 ng/ml, lens culinaris agglutinin reactive fraction of AFP 7.5%percnt;, des-gamma-carboxyprothrombin (DCP) 63,400 mAU/ml]. Sorafenib was administered at a reduced dose of 400 mg/day because of old age. Four months after sorafenib treatment, AFP and DCP had decreased to within normal levels, and the multiple lung metastases had disappeared. Currently, sorafenib is administered at a reduced dose of 400 mg/day, and the complete response has been maintained for 48 months. PMID- 26351419 TI - Resolution of Severe Ulcerative Colitis with the Specific Carbohydrate Diet. AB - A 73-year-old female of Asian origin was diagnosed with ulcerative colitis (UC) after initial gastrointestinal symptoms of abdominal pain and bloody diarrhea. She had a relatively benign course over the subsequent 12 years. In 2009, she had increased left-sided abdominal pain, bloody diarrhea and progressive weight loss, due to a severe exacerbation. In spite of a variety of standard treatments, her condition continued to decline with a significant impact on normal life and functioning. In December of 2010, repeat colonoscopy and microscopy confirmed pancolitis, without diverticulitis. The Specific Carbohydrate Diet (SCD) was initiated due to failure of conventional therapies. Following this highly restricted diet, within a period of 3-6 months, improvement was noted, and within a year, no abdominal pain or diarrhea were present, and she returned to her baseline functioning and career. Two years later, repeat colonoscopy showed resolution of the pancolitis, confirmed with microscopic evaluation. Successful use of the SCD in children with UC has been documented. We describe previously unreported, highly beneficial results with both symptomatic and clinical improvement and complete remission of UC in an adult female with the SCD. PMID- 26351420 TI - A Case of Tuberculous Granulomatous Panniculitis without Vasculitis. AB - We report a case of tuberculous granulomatous panniculitis without vasculitis in an 87-year-old female patient with B-cell chronic lymphocytic leukaemia. One month after starting chemotherapy with chlorambucil and prednisone she presented superficial erythematous plaques on the anterior side of the left leg. Three weeks later erythematous painless deep nodules appeared on the left popliteal fossa and on the left thigh. Cutaneous biopsy revealed granulomatous panniculitis without caseation necrosis or vasculitis. Polymerase chain reaction for Mycobacterium tuberculosis revealed positivity in the skin. The final diagnosis was reactivation of latent tuberculosis (TB) induced by deep immunosuppression associated with chemotherapy and haematological disease. Tuberculous granulomatous panniculitis without vasculitis is a rare presentation of cutaneous TB and may be part of the heterogeneous histopathologic spectrum of erythema induratum of Bazin (nodular vasculitis). Our case shows that the diagnosis of cutaneous TB requires the correlation of clinical findings with histopathology and microbiological tests. PMID- 26351421 TI - Erythema Dyschromicum Perstans: Identical to Ashy Dermatosis or Not? AB - Erythema dyschromicum perstans (EDP) and ashy dermatosis (AD) are pigmentary disorders of unknown etiology. EDP is usually considered to be identical to AD; however, a new clinical classification for EDP was proposed in the recent literature. Herein, we report a typical case of EDP observed in an African American man. Interestingly, the late skin lesions in this case fit the criteria of AD as well. While there appear to be a few clinical cases that can be diagnosed as both EDP and AD based on the clinical course, the preponderance of the evidence in the published reports of EDP and AD and the clinical findings reported here strongly suggest that they are two distinct entities in terms of the extent of the inflammation, albeit on the same spectrum of pigment disorders. PMID- 26351422 TI - Squamous Cell Carcinoma and Multiple Bowen's Disease in a Patient with a History of Consumption of Traditional Chinese Herbal Balls. AB - Arsenic has been classified as a class I human carcinogen, meaning that there is sufficient evidence of carcinogenicity to humans. Arsenic, however, remains a common contaminant in a number of traditional Chinese herbal balls. A 64-year-old man presented with an erythematous erosive patch on the left palm, multiple yellowish scaly patches on the right palm and an erythematous hyperkeratotic patch with bleeding on the left foot dorsum. He also had similar skin lesions on the back and buttock. He had a past medical history of chronic exposure to arsenic through consumption of traditional Chinese herbal balls. Skin biopsy revealed Bowen's disease on the left palm and squamous cell carcinoma on left foot dorsum. We report this case to emphasize that we should investigate patient's history thoroughly, including the use of Chinese herbal balls to find out arsenicism. PMID- 26351423 TI - A Case of Multiple Spontaneous Keloid Scars. AB - Keloid scars result from an abnormal healing response to cutaneous injury or inflammation that extends beyond the borders of the original wound. Spontaneous keloid scars forming in the absence of any previous trauma or surgical procedure are rare. Certain syndromes have been associated with this phenomenon, and few reports have discussed the evidence of single spontaneous keloid scar, which raises the question whether they are really spontaneous. Here, we present a 27 year-old mentally retarded single female with orbital hypertelorism, broad nasal bridge, repaired cleft lip and high-arched palate who presented with progressive multiple spontaneous keloid scars in different parts of her body which were confirmed histologically by the presence of typical keloidal collagen. This report supports the fact that keloid scars can appear spontaneously and are possibly linked to a genetic factor. Furthermore, it describes a new presentation of spontaneous keloid scars in the form of multiple large lesions in different sites of the body. PMID- 26351424 TI - Drug-Induced Hypersensitivity Syndrome Followed by Subacute Thyroiditis. AB - Drug-induced hypersensitivity syndrome (DIHS) is a severe multiorgan system adverse drug reaction with reactivation of human herpesviruses (HHVs) such as HHV 6, HHV-7, cytomegalovirus (CMV) and Epstein-Barr virus. Various complications, including autoimmune diseases, sometimes appear during the course of DIHS. We report a case of salazosulfapyridine-induced DIHS associated with HHV-6 reactivation. Two and a half months after the onset of DIHS, subacute thyroiditis occurred, possibly associated with CMV reactivation. Prednisolone (20 mg/day) was effective for subacute thyroiditis. Long-term follow-up is needed in patients with DIHS because of the possible onset of autoimmune diseases. PMID- 26351425 TI - Psoriasiform Drug Eruption Caused by Abatacept: Immunohistochemical Investigation of STAT Signaling. AB - Abatacept is a biological immune modifier that is used for the treatment of rheumatoid arthritis. Although psoriasiform drug eruption is reported as one of the cutaneous adverse effects of abatacept, the precise mechanisms are not fully understood. In this report, we describe a 65-year-old Japanese man with psoriasiform drug eruption caused by abatacept. Interestingly, immunohistochemical staining revealed that the epidermal keratinocytes in the basal layer and lower layers of the stratum spinosum were positive for pSTAT3, partially positive for pSTAT1 and negative for pSTAT6, which is similar to conventional psoriasis vulgaris. Our present study suggests that psoriasiform drug eruption caused by abatacept might develop by similar immunological mechanisms as those of psoriasis vulgaris. PMID- 26351426 TI - Incidental Syringomas of the Scalp in a Patient with Scarring Alopecia. AB - Syringomas are benign adnexal neoplasms of eccrine lineage, which occur most commonly in the periorbital region in middle-aged females. These cutaneous lesions rarely occur on the scalp, are typically asymptomatic and are predominantly of cosmetic significance. Involvement of the scalp may be indistinguishable from that of scarring alopecia. We present an unusual case of clinically inapparent syringomas occurring on the scalp of a 56-year-old female with alopecia who was subsequently diagnosed with lichen planopilaris after repeated scalp biopsy. In patients with unexplained hair loss, or in cases that are refractive to treatment, clinicians should perform scalp biopsy to exclude the diagnosis of rare neoplastic lesions like syringomas and to diagnose associated conditions. PMID- 26351427 TI - Two Cases of Cutaneous Squamous Cell Carcinoma Arising in Immunosuppressed Patients with Chronic Human Papillomavirus Infection. AB - Increasing evidence has suggested that human papillomaviruses (HPVs) are linked to a large subset of numerous malignant tumors, including mucosal squamous cell carcinoma (SCC); however, its involvement in cutaneous SCC has not fully been elucidated. Cutaneous SCC is the second most common type of skin cancer and is increasing in frequency every year. Since we have no satisfactory treatment for advanced SCC, it is important to provide a definitive diagnosis and appropriate therapeutic intervention at an early stage. Here, we present two cases of SCC arising in immunosuppressed patients. In these cases, we suspected the association between SCC and HPV infection histopathologically and succeeded in proving the presence of high-risk type HPV by PCR analysis (HPV 14 in case 1 and HPV 23 and 38 in case 2). Although it is unclear whether HPV actually induced SCC in our cases, our cases showed rapid progression comparing to typical courses of actinic keratosis (AK)/SCC. SCC and AK are common diseases; in daily practice, dermatologists examine many patients with immunosuppression of various causes. We should apply increased oncological vigilance to these patients to prevent an aggressive course of SCC/AK. PMID- 26351428 TI - Diaminodiphenyl Sulfone-Induced Hemolytic Anemia and Alopecia in a Case of Linear IgA Bullous Dermatosis. AB - Linear immunoglobulin A (IgA) bullous dermatosis (LABD) is an autoimmune mucocutaneous disease characterized by subepidermal blistering induced by IgA autoantibodies against several autoantigens in the basal membranous zone of the skin and mucosal tissue. Although diaminodiphenyl sulfone (DDS), also known as dapsone, is generally recognized as the first-line therapy for LABD, DDS can induce several severe side effects. We present a Japanese case of LABD with DDS induced hemolytic anemia and alopecia. In the present case, the DDS-induced hemolytic anemia and hair loss made the DDS monotherapy difficult. When DDS is used in LABD patients with iron deficiency anemia (IDA), hemolytic anemia is concealed by IDA. It is thus necessary to carefully and frequently examine the laboratory data to find the signs of DDS-induced hemolytic anemia. Even though there is no literature on DDS-induced alopecia, alopecia was reported as one of the side effects of DDS in an FDA report, and, in our case, hair loss was improved after reducing its dosage. We have to recognize that alopecia is one of the side effects of DDS and that careful management is needed in order not to overlook the adverse side effects of DDS when treating LABD patients. PMID- 26351429 TI - Elderly-Onset Generalized Pustular Psoriasis without a Previous History of Psoriasis Vulgaris. AB - Generalized pustular psoriasis (GPP) is characterized by sudden fever and extensive erythema with pustules and occurs in patients with or without preceding psoriasis vulgaris. We report an 83-year-old man showing irregularly shaped erythema with pustules on the trunk and extremities. He initially had no fever and came to our clinic a few days after the onset of the skin lesions because of high fever and general malaise. We found an extension and new development of erythema and pustules on the whole body. The patient also manifested night delirium. Histological examination revealed neutrophil infiltration into the upper epidermis, which formed a spongiform pustule of Kogoj. Pustular fluid cultures were negative for bacteria. We diagnosed GPP without preceding psoriasis vulgaris. Mutation analysis revealed no significant mutations in IL36RN and CARD14. Previous reports indicated that onset of GPP at the age of 83 years is definitely rare. In older individuals, general disease characteristics include an atypical clinical course, an especially slow appearance and cure, and mental disorder. Our case also revealed such characteristics. Thus, it is necessary to be aware of the clinical course and mental problems in elderly patients with GPP. PMID- 26351430 TI - Blue Rubber Bleb Nevus Syndrome Showing Vascular Skin Lesions Predominantly on the Face. AB - An 81-year-old Japanese man presented with dark blue papules and nodules on his face. There were multiple soft papules and nodules, dark blue in color, compressive, and ranging in size from 2 to 10 mm. A few similar lesions were seen on the patient's right dorsal second toe and right buccal mucosa. There were no skin lesions on his trunk and upper limbs. The patient's past history did not include gastrointestinal bleeding or anemia. Histopathological examination showed dilated vascular spaces lined by the normal epithelium extending beneath the dermis and into the subcutaneous fat. Endoscopy of the gastrointestinal tract to check for colon involvement was not performed. X-ray images of the limbs revealed no abnormalities in the bones or joints. Laboratory investigations did not show anemia. Although we failed to confirm a diagnosis by endoscopy, the skin lesions, histopathological findings, lack of abnormal X-ray findings, and the presence of oral lesions as a part of gastrointestinal tract guided the diagnosis of blue rubber bleb nevus syndrome (BRBNS). Skin lesions of BRBNS occur predominantly on the trunk and upper limbs. However, the present case showed multiple skin lesions predominantly on the face. Therefore, it is important for clinicians to know about a possible atypical distribution of skin lesions in BRBNS. PMID- 26351432 TI - Mycobacterium chelonae Is an Ubiquitous Atypical Mycobacterium. AB - The type of cutaneous infection varies mainly according to the patient's immune status, and the disseminated form is mostly found in the context of immunosuppression. We report the case of a 62-year-old male who was under long term systemic corticosteroid therapy and presented with a 7-month history of multiple painless cutaneous lesions at various stages of development: papules, nodules, pustules and hemorrhagic crusts, as well as small erosions and ulcers distributed over the limbs and scalp. Cutaneous biopsy showed a suppurative granulomatous infiltrate with abscess formation. Fite stain revealed numerous extracellular bacilli, suggesting mycobacterial infection, particularly by atypical mycobacteria. Culture of a skin sample revealed Mycobacterium chelonae. The patient started multidrug therapy and showed clinical improvement despite of resistance to one of the antibiotics. This striking presentation underlines the role of immunosuppression with corticotherapy as a major risk factor for these infections. Multidrug therapy is advised and antibiogram is essential in directing treatment. PMID- 26351431 TI - Martorell's Ulcer: Diagnostic and Therapeutic Challenge. AB - Martorell's ulcer is an uncommon ischemic and extremely painful lesion located in the distal portion of the lower limb, resulting from severe systemic and poorly controlled hypertension. It is common in women between 50 and 70 years of age. The diagnosis is clinical and mostly belated, following exclusion of other causes. The response to treatment takes time and is unsatisfactory. A combination of several drugs associated with surgery may be required for wound healing. The authors present a case of Martorell's hypertensive ulcer, with emphasis on the diagnostic and therapeutic difficulties. PMID- 26351433 TI - Novel Mutation of the TINF2 Gene in a Patient with Dyskeratosis Congenita. AB - Dyskeratosis congenita (DKC) is a rare inherited disease that is characterized by abnormal skin pigmentation, nail dystrophy and mucosal leukoplakia. DKC is caused by an abnormality in a component of the telomerase and shelterin complexes. TINF2 encodes a protein in the shelterin complex and TERC encodes a component of the telomerase complex. Mutations of both genes have been associated with DKC. This study examined mutations in TINF2. PMID- 26351434 TI - Ureteroscopy-Assisted Biopsy for a Retroperitoneal Tumor: A Case Report. AB - INTRODUCTION: Retroperitoneal tumor is often seen in urology clinical practice. To diagnose the tumor, tumor specimens must be obtained. However, in some cases, the tumor is penetrated by vessels around the ureter, and it may be difficult to detect the optimal spot for obtaining a specimen, even when performing open surgery. CASE PRESENTATION: A 53-year-old male patient was referred to our hospital for further examination of left back pain due to hydronephrosis. Enhanced computed tomography demonstrated ureter stenosis in front of the ilium, which was surrounded by a retroperitoneal tumor. The tumor was penetrated by blood vessels; therefore, we performed an open surgical biopsy on the suspicion of a retroperitoneal tumor using ureteroscopic assistance. The diagnosis of idiopathic retroperitoneal fibrosis was made according to the biopsy. CONCLUSION: We herein report the first case of a ureteroscopy-assisted biopsy for the pathological diagnosis of a retroperitoneal tumor. PMID- 26351435 TI - Human Epidermal Growth Factor Receptor 2-Positive Duodenal Adenocarcinoma: A Case Report and Review of the Literature. AB - Duodenal adenocarcinoma is a rare malignancy and carries a poor prognosis. The role of adjuvant therapy and the optimal chemotherapy regimen remain largely unclear. Treatment with trastuzumab results in prolonged survival in gastroesophageal cancer if human epidermal growth factor receptor 2 (HER2) is overexpressed or amplified in tumor cells. However, unlike gastric adenocarcinomas, duodenal cancers seem to rarely harbor HER2 amplification or overexpression. We report the case of a patient with HER2-positive stage III duodenal adenocarcinoma who has received adjuvant chemotherapy including trastuzumab. PMID- 26351436 TI - A Grave Outcome of Posterior Reversible Encephalopathy Syndrome in a Patient Receiving Avastin (Bevacizumab) for Metastatic High-Grade Serous Ovarian Cancer. AB - A 45-year-old female developed neurological symptoms and elevated diastolic blood pressure while on bevacizumab (Avastin) and gemcitabine for recurrent carboplatin resistant high-grade serous ovarian cancer. A brain MRI diagnosed our patient with posterior reversible encephalopathy syndrome. We are discussing her presenting symptoms in this paper as well as the management and the outcome. We emphasize the importance of keeping this rare but very serious complication in all patients receiving bevacizumab. PMID- 26351437 TI - Paraneoplastic Guillain-Barre Syndrome in Small Cell Lung Cancer. AB - Guillain-Barre syndrome (GBS) is defined as an acute, autoimmune polyradiculoneuropathy. It is a rare disease that occurs at a rate of 1.11 cases per 100,000 person-years. However, once infected, up to 20%percnt; of patients develop severe disability, and approximately 5%percnt; die. There have been reports of GBS in different cancers. Among them, there are 6 previous reports of GBS in small cell lung cancer. Here, we report a case of a 52-year-old man who was diagnosed with GBS in the setting of small cell lung cancer with chemotherapy. PMID- 26351438 TI - Sperm Count Improvement in a Cancer-Surviving Patient. AB - OBJECTIVE: To describe the case of a cancer-surviving patient who was treated with an aromatase inhibitor for fertility reasons with successful results. CLINICAL CASE: A 30-year-old patient from our institute who had been submitted to bone marrow transplantation in the past as part of treatment for Hodgkin's disease had revealed oligospermia several times. His sperm count mean value was 33,500 cells/ml. He was treated with an aromatase inhibitor (letrozole, 2 mg/day) for 8 months. After this period, his sperm count had increased significantly to 1,000,000 cells/ml. CONCLUSION: A large number of cancer survivors express a wish for having babies. After their cure, a lot of them have a low count of spermatozoids, and we think that our results show an easy way of helping them. PMID- 26351439 TI - Easy Diagnosis of Aortic Invasion in Patients with Lung Cancer Using Cine Magnetic Resonance Imaging. AB - Selecting the proper treatment strategy for locally advanced lung cancer, such as T4 tumors, is difficult. Therefore, obtaining an accurate diagnosis of T4 tumors is required. It can be difficult to determine whether the tumor invades adjacent structures. We describe the case of a patient easily diagnosed to be without aortic invasion using cine magnetic resonance imaging (MRI). We herein report the case of an 80-year-old male who presented a lung tumor. The transbronchial lung washing cytology findings were consistent with those of adenocarcinoma. In addition, the computed tomography findings indicated suspected aortic invasion of the lung tumor, as the mass girdled the descending aorta beyond 120 degrees adjoining at a length of 10 cm. However, cine MRI display clearly demonstrated a clear area of isolation between the aorta and lung tissue based on differences in the heart rhythm from the patient's respiratory movements. Therefore, the lesion was clinically diagnosed as a stage IIB (T3N0M0) tumor. Radiation was administered due to the patient's advanced age and comorbidities such as chronic obstructive pulmonary disease. He remains alive without disease progression 6 months after the therapy. Our findings, therefore, indicate the usefulness of easily diagnosing the absence of aortic invasion in patients with lung cancer using cine MRI without the need for a special software program. PMID- 26351440 TI - A Case of Gastric Cancer with Residual Tumor Only in the Para-Aortic Lymph Nodes after Systemic Chemotherapy followed by Conversion Surgery. AB - We report the case of a 60-year-old male who was diagnosed with gastric cancer. Upper gastrointestinal endoscopy indicated advanced cancer in the posterior wall of the gastric body. Biopsy revealed poorly differentiated adenocarcinoma. Abdominal computed tomography demonstrated thickening of the gastric wall and enlargement of the regional lymph nodes and of the para-aortic lymph nodes (PAN). The involvement of the PAN extended from the celiac axis to the caudal area of the inferior mesenteric artery [cT3N3aH0P0M1(LYM), stage IV]. Systemic chemotherapy was initiated. After 3 courses of S-1 plus cisplatin combination chemotherapy, the primary lesion and the enlarged lymph nodes revealed marked regression except for a minute residual lesion in the lymph nodes. Upon obtaining informed consent, open distal gastrectomy, D2 lymphadenectomy with PAN dissection, and Roux-en-Y reconstruction were performed. The patient was discharged from the hospital 35 days after the operation. Histopathological examination of the resected samples revealed malignant cells only in the PAN, not in the stomach or in the regional lymph nodes [ypT0N0M1(LYM), stage IV]. Currently, the patient is undergoing postoperative adjuvant chemotherapy with S-1 and has remained well without any recurrence after 6 months following surgery. PMID- 26351441 TI - Mediastinal Germ Cell Tumor Exhibiting a Discrepancy between Tumor Markers and Imaging: A Case Study. AB - We report a mediastinal germ cell tumor (GCT) that exhibited a discrepancy between the time course of serum human chorionic gonadotropin (hCG) levels and clinical consequences. An otherwise healthy man, aged 34 years, was diagnosed with a nonseminomatous GCT, most likely embryonal carcinoma (EC), based on a mediastinal tumor biopsy. Standard chemotherapy resulted in an optimal decrease in serum hCG levels. However, multiple lesions in the liver continued to enlarge, which led to his death. Autopsy revealed few viable tumor cells in the liver, with the great majority of the tumor cells appearing to have undergone necrosis, suggesting that they responded to the chemotherapy. The residual tumor cells in the mediastinum and the liver were similar to syncytiotrophoblast cells, suggesting a cho-riocarcinoma (CC). On immunohistochemical analysis, the mediastinal tumor cells in the diagnostic biopsy specimen expressed both CD30 and hCG, whereas residual mediastinal and hepatic tumor cells in the autopsy specimen after chemotherapy also expressed hCG, but not CD30. These findings suggested that the patient suffered from a primary mixed GCT consisting of an EC and a CC. Both pre- and postchemotherapy tumors strongly expressed matrix metalloproteinase 2, supporting the aggressive and invasive features of the tumor phenotype. We speculate that the extremely invasive tumor destroyed normal liver structure, whereas chemotherapy and central necrosis reduced the number of viable cells themselves, causing a discordant decrease in serum hCG levels. PMID- 26351442 TI - Osteoradionecrosis of the Ribs following Breast Radiotherapy. AB - INTRODUCTION: Osteoradionecrosis (ORN) of the chest wall is a rare complication after whole-breast radiotherapy (RT). Herein, we report a case of ORN involving the underlying ribs following adjuvant whole-breast RT using standard fractionation and conduct a review of the literature. CASE REPORT: A previously well 43-year-old female with right-sided, early-stage, node-negative breast cancer was treated with breast-conserving surgery. She subsequently underwent adjuvant whole-breast RT receiving 50 Gy in 25 fractions over 5 weeks using standard tangential photon fields with 6 MV photons followed by an electron boost of 10 Gy in 5 fractions according to International Commission on Radiation Units (ICRU) requirements. Eleven months after RT, the patient developed right lateral chest wall pain, with magnetic resonance imaging (MRI) demonstrating two fractures involving the underlying right fifth and sixth ribs associated with fatty marrow changes in the second to sixth ribs, thus raising the possibility of ORN. Treatments including hyperbaric oxygen, pentoxifylline and vitamin E were used with symptomatic improvements. There was demonstrable resolution on follow up MRI at 2.5 years. CONCLUSION: The incidence of ORN utilising modern RT techniques and standard fractionation is rare. Numerous treatments are available, with variable response rates. Emerging evidence of predictive gene profiling to estimate the risk of radiation sensitivity may assist in individualising preventative strategies to mitigate the risk of ORN. PMID- 26351443 TI - Metastatic Prostatic Ductal Adenocarcinoma Successfully Treated with Docetaxel Chemotherapy: A Case Report. AB - A 68-year-old man presented with gross hematuria. A papillary urethral tumor adjacent to the verumontanum was found by cystourethroscopy. Serum prostate specific antigen (PSA) was 3.246 ng/ml. A transurethral biopsy specimen was most suggestive of a primary urothelial carcinoma of the prostate, for which a radical cystoprostatectomy was performed. The final pathology was prostatic ductal adenocarcinoma with very focal acinar features (Gleason score 5 %plus; 4 = 9, pT3bN0M0). Local recurrence and pelvic bone metastases developed 17 months later, and his PSA rose to 10.806 ng/ml. He was treated with combined androgen blockade and radiation. Two years later, the lesion showed progressive growth. Treatment followed with docetaxel (70 mg/m(2) every 3 weeks) and prednisolone 5 mg twice daily. After 10 cycles of chemotherapy, all lesions disappeared and PSA decreased to <0.005 ng/ml. Three years after chemotherapy, he maintains a complete response without any additional treatments. Docetaxel chemotherapy can be an effective treatment for patients with recurrent prostatic ductal adenocarcinoma. PMID- 26351444 TI - Extensive Bone Marrow Necrosis in a Case of Acute Myeloid Leukemia Transformed from a Myeloproliferative Neoplasm. AB - Extensive necrosis affecting more than 50%percnt; of the bone marrow is an extremely rare histopathological finding. Relatively little is known about its clinical significance because it is most commonly identified at autopsy - whether it is an independent prognostic marker or whether it is a surrogate marker of underlying disease burden remains unclear. We describe herein a case of a 66-year old patient with acute myeloid leukemia who presented with acute bone marrow failure and was found to have extensive necrosis. We include presenting clinical features, pathology attained at biopsy, and the challenge of treatment. Bone marrow necrosis is a rare but important clinicopathological entity whose recognition may herald the way for more effective prognostication of underlying disease. PMID- 26351445 TI - Intracardiac Myxoma, Cerebral Aneurysms and Elevated Interleukin-6. AB - Cerebral aneurysms are well known to be associated with cardiac myxomas. The mechanism of cerebral aneurysm formation remains to be elucidated. Embolization of tumor particles in the vessel wall has been proposed as the likely mechanism for aneurysm formation. Recent reports suggest interleukin-6 (IL-6) may play a role as well. We describe a patient who presented with subarachnoid hemorrhage secondary to ruptured right middle cerebral artery (MCA) aneurysm and unruptured left MCA aneurysm. Subsequently, the patient was found to have an atrial myxoma and persistently elevated serum IL-6 levels. Transcranial Doppler monitoring showed multiple emboli in the right MCA vascular territory on day 1 after surgery but no recurrent embolization during the next 2 weeks on repeated tests. Elevated IL-6 levels were noted both on day 1 and on day 30. Our findings provide evidence that IL-6 elevation and not tumor embolization is likely the culprit for aneurysm formation in some patients with atrial myxoma. PMID- 26351446 TI - Primary Intraventricular Brain Abscess Resulting in Isolated Dilation of the Inferior Horn and Unilateral Hydrocephalus. AB - Primary intraventricular brain abscesses are rare, and there are no established treatment guidelines for this condition. We report a case in which isolated ventricular dilatation and unilateral hydrocephalus developed after seemingly successful conservative management and which required surgical diversion of the cerebrospinal fluid. A 59-year-old woman presented to our emergency department with high-grade fever and headache. Brain magnetic resonance imaging (MRI) revealed abscesses in the bilateral posterior horn. Although surgical evacuation of the abscesses was considered, conservative management with antibiotics was selected because of the paucity of severe neurological deficits and the concern that an attempt to evacuate the intraventricular abscess might lead to inadvertent rupture of the abscess capsule and acute ventriculitis. Despite reduction in the abscess volume, the patient developed an altered mental status 4 weeks after admission. Follow-up MRI revealed isolated dilation of the left inferior horn, compressing the brainstem. Emergency fenestration of the dilated inferior horn was performed, and endoscopic observation revealed an encapsulated abscess with adhesion to the ventricular wall which was thought responsible for the ventricular dilation and unilateral hydrocephalus. Two weeks after the initial surgery, the unilateral hydrocephalus was treated by placement of a ventriculoperitoneal shunt. Eradication of the intraventricular brain abscesses without surgical evacuation may justify the conservative management of this patient. However, the possibility that earlier surgical evacuation might have prevented development of the isolated ventricular dilation cannot be denied. Additional clinical experience is required to determine which treatment (surgical vs. conservative) is more appropriate in patients with primary intraventricular brain abscesses. PMID- 26351447 TI - Pediatric Acute Longitudinal Extensive Transverse Myelitis Secondary to Neuroborreliosis. AB - Lyme neuroborreliosis has several different clinical manifestations in children, of which facial nerve palsies, meningitis and radiculopathies are the most common. Transverse myelitis (TM) secondary to Lyme disease has been reported in rare occasions, typically presenting with severe weakness, sensory abnormalities and autonomic dysfunction. We present the case of a 16-year-old male who developed acute left peripheral facial palsy and longitudinal extensive TM secondary to Lyme disease. Remarkably, the patient reported only mild symptoms with severe back pain in the absence of profound signs of myelopathy. We reviewed the medical literature and analyzed the clinical features of pediatric patients with Borrelia burgdorferi-related TM. PMID- 26351448 TI - Case Report: Trigeminal Neuralgia Caused by a Minute Meningioma with Hyperostosed Suprameatal Tubercle. AB - Cerebellopontine angle tumors might occasionally provoke trigeminal neuralgia but are usually large enough to be diagnosed radiographically. We present a case of trigeminal neuralgia caused by a very small meningioma covering the suprameatal tubercle that displayed hyperostosis at the entrance of Meckel's cave and was not obvious on routine magnetic resonance (MR) images. A 72-year-old woman with intractable trigeminal neuralgia in the left V3 territory was referred to our institution. Preoperative imaging studies revealed that the left trigeminal nerve was medially distorted at the entrance of Meckel's cave by a laterally seated bone bulge covered by a minute enhanced lesion. Trigeminal nerve decompression surgery was performed via a retrosigmoid intradural suprameatal approach. We found a small meningioma that had compressed and flattened the trigeminal nerve root at the entrance of Meckel's cave, which was grossly and totally removed by suprameatal tubercle resection. There was no vascular compression of the trigeminal nerve root. The trigeminal neuralgia ceased completely after the operation. Accurate preoperative determination of the causative pathologies is essential to achieve adequate surgical results after microvascular decompression for neurovascular compression syndrome. Because conventional MR sequences are inadequate for the precise interpretation of complex neurovascular anatomy in the cerebellopontine angle and such small tumors can be overlooked on routine MR studies, high-resolution thin-slice MR examinations and careful radiological interpretations are required for correct diagnosis and treatment. PMID- 26351449 TI - Impact of Noise on a Dynamical System: Prediction and Uncertainties from a Swarm Optimized Neural Network. AB - An artificial neural network (ANN) based on particle swarm optimization (PSO) was developed for the time series prediction. The hybrid ANN+PSO algorithm was applied on Mackey-Glass chaotic time series in the short-term x(t + 6). The performance prediction was evaluated and compared with other studies available in the literature. Also, we presented properties of the dynamical system via the study of chaotic behaviour obtained from the predicted time series. Next, the hybrid ANN+PSO algorithm was complemented with a Gaussian stochastic procedure (called stochastic hybrid ANN+PSO) in order to obtain a new estimator of the predictions, which also allowed us to compute the uncertainties of predictions for noisy Mackey-Glass chaotic time series. Thus, we studied the impact of noise for several cases with a white noise level (sigma(N)) from 0.01 to 0.1. PMID- 26351450 TI - Optimization of Deep Sedation with Spontaneous Respiration for Therapeutic Endoscopy Combining Propofol and Bispectral Index Monitoring. AB - Background/Aims. This study aimed to establish optimal propofol anesthesia for therapeutic endoscopy, which has not been established. Methodology. We retrospectively investigated data on 89 patients who underwent upper-GI endoscopic submucosal dissection or endoscopic mucosal resection under anesthesia with propofol. Examined doses of propofol were changed according to efficacy and/or adverse events and classified into 5 periods. A bispectral index (BIS) monitor was used at Period 5 to decrease the incidence of adverse events caused by oversedation. The initial dose of propofol was administered after bolus injection of pethidine hydrochloride (0.5 mg/kg), and 1.0 mL of propofol was added every minute until the patients fell asleep. Continuous and bolus infusion were performed to maintain sedation. When the patient moved or an adverse event occurred, the maintenance dose examined was increased or decreased by 5 mL/h regardless of body weight. Results. Dose combinations (introduction : maintenance) and patient numbers for each period were as follows: Period 1 (n = 27), 0.5 mg/kg : 5 mg/kg/h; Period 2 (n = 11), 0.33 mg/kg : 3.3 mg/kg/h; Period 3 (n = 7), 0.5 mg/kg : 3.3 mg/kg/h; Period 4 (n = 14), 0.5 mg/kg : 2.5 mg/kg/h; Period 5 (n = 30), 0.5 mg/kg : 2.5 mg/kg/h, using BIS monitor. During Period 5, an adverse event occurred in 10.0% of patients, which was lower than that for Periods 1-4. Conclusions. Period 5 propofol anesthesia with BIS protocol could be safe and useful for therapeutic endoscopy under deep sedation with spontaneous respiration. PMID- 26351451 TI - Enteroscopic Diagnosis and Management of Small Bowel Diverticular Hemorrhage: A Multicenter Report from the Taiwan Association for the Study of Small Intestinal Diseases. AB - Small bowel diverticulum is a rare cause of gastrointestinal bleeding. The diagnosis and treatment of small bowel diverticular hemorrhage is clinically challenging before the development of deep enteroscopy. In this multicenter study from the Taiwan Association for the Study of Small Intestinal Diseases (TASSID), 608 patients underwent deep enteroscopy for obscure gastrointestinal bleeding during January 2004 and April 2010 from eight medical centers in Taiwan. Small bowel diverticular hemorrhage account for 7.89% of obscure gastrointestinal bleeding in this study. Most of the patients received endoscopic therapy with an initial hemostasis rate of 85.71% and rebleeding rate of 20%. In this large case series investigating the enteroscopic management of small intestinal diverticular hemorrhage, we found that, as to patients with peptic ulcer hemorrhage, most of these patients can be successfully managed by endoscopic therapy before surgery in the era of deep enteroscopy. PMID- 26351452 TI - Effects Comparison between Endoscopic Papillary Large Balloon Dilatation and Endoscopic Sphincterotomy for Common Bile Duct Stone Removal. AB - Endoscopic sphincterotomy (EST) is a treatment of choice for stone extraction and is now most frequently used. The study was to compare the efficacy of endoscopic papillary large balloon dilatation (EPLBD) and endoscopic sphincterotomy (EST) for common bile duct stone removal. Trials comparing the effects between EPLBD and EST treatment were searched according to the study protocol. Overall stone removal rate, complete removal rate in 1st session, treatment duration, mechanical lithotripsy using rate, and overall complication rate were compared using risk ratio (RR) and mean difference (MD) and their 95% confidence interval (CI) via RevMan 5.2 software. For overall stone removal rate, two therapies showed similar effect, but EPLBD showed better overall stone removal rate for stone >10 mm in diameter. For complete stone removal rate in 1st session, no difference was found, even for those with stone >10 mm in diameter; EPLBD showed longer treatment duration, higher mechanical lithotripsy using rate obvious overall complications rate, and more serious bleeding, whereas there were no significant differences for perforation, hyperamylasemia, pancreatitis, and cholecystitis/cholangitis. EPLBD showed better efficacy in certain conditions compared to EST, however with shortcomings, such as more duration, higher mechanical lithotripsy using rate, more serious overall complications rate, and bleeding. PMID- 26351453 TI - Waist-to-Hip Ratio, but Not Body Mass Index, Is Associated with Testosterone and Estradiol Concentrations in Young Women. AB - We studied if testosterone and estradiol concentrations are associated with specific female waist-to-hip ratios (WHRs) and body mass indices (BMIs). Participants were 187 young women from which waist, hips, weight, and height were measured. In addition, participants informed on which day of their menstrual cycle they were and provided a 6 mL saliva sample. Ninety-one of them were in the follicular phase and 96 in the luteal phase. Only in the fertile phase of the menstrual cycle we found a significant interaction between testosterone and estradiol affecting WHR (b +/- s.e. = -0.000003 +/- 0.000001; t 94 = -2.12, adjusted R (2) = -0.008, P = 0.03). Women with the highest levels of both hormones had the lowest WHRs, while women with low estradiol and high testosterone showed the highest WHRs. BMI significantly increased as testosterone increased in female in their nonfertile days. PMID- 26351454 TI - Farming of Plant-Based Veterinary Vaccines and Their Applications for Disease Prevention in Animals. AB - Plants have been studied for the production of pharmaceutical compounds for more than two decades now. Ever since the plant-made poultry vaccine against Newcastle disease virus made a breakthrough and went all the way to obtain regulatory approval, research to use plants for expression and delivery of vaccine proteins for animals was intensified. Indeed, in view of the high production costs of veterinary vaccines, plants represent attractive biofactories and offer many promising advantages in the production of recombinant vaccine proteins. Furthermore, the possibility of conducting immunogenicity and challenge studies in target animals has greatly exaggerated the progress. Although there are no edible plant-produced animal vaccines in the market, plant-based vaccine technology has great potentials. In this review, development, uses, and advantages of plant-based recombinant protein production in various expression platforms are discussed. In addition, examples of plant-based veterinary vaccines showing strong indication in terms of efficacy in animal disease prevention are also described. PMID- 26351455 TI - Impact of Hybrid and Complex N-Glycans on Cell Surface Targeting of the Endogenous Chloride Cotransporter Slc12a2. AB - The Na(+)K(+)2Cl(-) cotransporter-1 (Slc12a2, NKCC1) is widely distributed and involved in cell volume/ion regulation. Functional NKCC1 locates in the plasma membrane of all cells studied, particularly in the basolateral membrane of most polarized cells. Although the mechanisms involved in plasma membrane sorting of NKCC1 are poorly understood, it is assumed that N-glycosylation is necessary. Here, we characterize expression, N-glycosylation, and distribution of NKCC1 in COS7 cells. We show that ~25% of NKCC1 is complex N-glycosylated whereas the rest of it corresponds to core/high-mannose and hybrid-type N-glycosylated forms. Further, ~10% of NKCC1 reaches the plasma membrane, mostly as core/high-mannose type, whereas ~90% of NKCC1 is distributed in defined intracellular compartments. In addition, inhibition of the first step of N-glycan biosynthesis with tunicamycin decreases total and plasma membrane located NKCC1 resulting in almost undetectable cotransport function. Moreover, inhibition of N-glycan maturation with swainsonine or kifunensine increased core/hybrid-type NKCC1 expression but eliminated plasma membrane complex N-glycosylated NKCC1 and transport function. Together, these results suggest that (i) NKCC1 is delivered to the plasma membrane of COS7 cells independently of its N-glycan nature, (ii) most of NKCC1 in the plasma membrane is core/hybrid-type N-glycosylated, and (iii) the minimal proportion of complex N-glycosylated NKCC1 is functionally active. PMID- 26351456 TI - Update on Edoxaban for the Prevention and Treatment of Thromboembolism: Clinical Applications Based on Current Evidence. AB - Vitamin K antagonists (VKA) and heparins have been utilized for the prevention and treatment of thromboembolism (arterial and venous) for decades. Targeting and inhibiting specific coagulation factors have led to new discoveries in the pharmacotherapy of thromboembolism management. These targeted anticoagulants are known as direct oral anticoagulants (DOACs). Two pharmacologically distinct classes of targeted agents are dabigatran etexilate (Direct Thrombin Inhibitor (DTI)) and rivaroxaban, apixaban, and edoxaban (direct oral factor Xa inhibitors (OFXaIs)). Emerging evidence from the clinical trials has shown that DOACs are noninferior to VKA or low-molecular-weight heparins in the prevention and treatment of thromboembolism. This review examines the role of edoxaban, a recently approved OFXaI, in the prevention and treatment of thromboembolism based on the available published literature. The management of edoxaban in the perioperative setting, reversibility in bleeding cases, its role in cancer patients, the relevance of drug-drug interactions, patient satisfaction, financial impacts, and patient education will be discussed. PMID- 26351457 TI - Changing Trends in the Management of Epistaxis. AB - Epistaxis is a very common complaint seen by many types of physicians including otolaryngologists, family physicians, and others. Management of epistaxis is often challenging and requires many types of intervention. The following review describes the different types of past and current treatment modalities including cautery, nasal packing, maxillary artery ligation, anterior artery ligation, and sphenopalatine artery ligation. The paper also proposes an algorithm for managing such cases. PMID- 26351459 TI - Diffuse Calcifications of the Spleen in a Woman with Systemic Lupus Erythematosus. AB - Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease, which affects a wide variety of organs including the spleen. Splenic involvement in SLE includes conditions such as splenomegaly, hyposplenism, infarction, and spontaneous rupture. However, only a few cases of splenic calcifications in patients with SLE have been reported. Herein, we present a case of a 24-year-old female diagnosed with SLE, in which we found diffuse splenic calcifications. The unique pattern of splenic calcifications in SLE contributes to the differential diagnosis from other conditions such as infections and other connective tissue diseases, which also cause calcifications in the spleen. PMID- 26351458 TI - Rheumatoid Arthritis and the Cervical Spine: A Review on the Role of Surgery. AB - Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease affecting a significant percentage of the population. The cervical spine is often affected in this disease and can present in the form of atlantoaxial instability (AAI), cranial settling (CS), or subaxial subluxation (SAS). Patients may present with symptoms and disability secondary to these entities but may also be neurologically intact. Cervical spine involvement in RA can pose a challenge to the clinician and the appropriate role of surgical intervention is controversial. The aim of this paper is to describe the pathology, pathophysiology, clinical manifestations, and diagnostic evaluation of rheumatoid arthritis in the cervical spine in order to provide a better understanding of the indications and options for surgery. Both the medical and surgical treatment options for RA have improved, so has the prognosis of the cervical spine disease. With the advent of disease modifying antirheumatic drugs (DMARDs), fewer patients are presenting with cervical spine manifestations of RA; however, those that do, now have improved surgical techniques available to them. We hope that, by reading this paper, the clinician is able to better evaluate patients with RA in the cervical spine and determine in which patients surgery is indicated. PMID- 26351460 TI - Cooccurrence of Multiple Sclerosis and Idiopathic Basal Ganglia Calcification. AB - Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease of central nervous system that affects both white and gray matter. Idiopathic calcification of the basal ganglia is a rare neurodegenerative disorder of unknown cause that is characterized by sporadic or familial brain calcification. Concurrence of multiple sclerosis (MS) and idiopathic basal ganglia calcification (Fahr's disease) is very rare event. In this study, we describe a cooccurrence of idiopathic basal ganglia calcification with multiple sclerosis. The association between this disease and MS is unclear and also maybe probably coincidental. PMID- 26351462 TI - Human Amniotic Fluid Mesenchymal Stem Cells from Second- and Third-Trimester Amniocentesis: Differentiation Potential, Molecular Signature, and Proteome Analysis. AB - Human amniotic fluid stem cells have become an attractive stem cell source for potential applications in regenerative medicine and tissue engineering. The aim of this study was to characterize amniotic fluid-derived mesenchymal stem cells (AF-MSCs) from second- and third-trimester of gestation. Using two-stage protocol, MSCs were successfully cultured and exhibited typical stem cell morphological, specific cell surface, and pluripotency markers characteristics. AF-MSCs differentiated into adipocytes, osteocytes, chondrocytes, myocytes, and neuronal cells, as determined by morphological changes, cell staining, and RT qPCR showing the tissue-specific gene presence for differentiated cell lineages. Using SYNAPT G2 High Definition Mass Spectrometry technique approach, we performed for the first time the comparative proteomic analysis between undifferentiated AF-MSCs from late trimester of gestation and differentiated into myogenic, adipogenic, osteogenic, and neurogenic lineages. The analysis of the functional and expression patterns of 250 high abundance proteins selected from more than 1400 demonstrated the similar proteome of cultured and differentiated AF-MSCs but the unique changes in their expression profile during cell differentiation that may help the identification of key markers in differentiated cells. Our results provide evidence that human amniotic fluid of second- and third-trimester contains stem cells with multilineage potential and may be attractive source for clinical applications. PMID- 26351463 TI - Extracellular Vesicles from MSC Modulate the Immune Response to Renal Allografts in a MHC Disparate Rat Model. AB - Application of mesenchymal stromal cells (MSC) has been proposed for solid organ transplantation based on their potent immunomodulatory effects. Since side effects from the injection of large cells cannot be excluded, the hypothesis rises that extracellular vesicles (EV) may cause immunomodulatory effects comparable to MSC without additional side effects. We used MSC-derived EV in a rat renal transplant model for acute rejection. We analysed peripheral blood leukocytes (PBL), kidney function, graft infiltrating cells, cytokines in the graft, and alloantibody development in animals without (allo) and with EV application (allo EV). There was no difference in kidney function and in the PBL subpopulation including Tregs between allo and allo EV. In the grafts T- and B cell numbers were significantly higher and NK-cells lower in the allo EV kidneys compared to allo. TNF-alpha transcription was lower in allo EV grafts compared to allo; there was no difference regarding IL-10 and in the development of alloantibodies. In conclusion, the different cell infiltrates and cytokine transcription suggest distinct immunomodulatory properties of EV in allotransplantation. While the increased T- and B-cells in the allo EV grafts may represent a missing or negative effect on the adaptive immune system, EV seem to influence the innate immune system in a contrary fashion. PMID- 26351461 TI - Physical, Spatial, and Molecular Aspects of Extracellular Matrix of In Vivo Niches and Artificial Scaffolds Relevant to Stem Cells Research. AB - Extracellular matrix can influence stem cell choices, such as self-renewal, quiescence, migration, proliferation, phenotype maintenance, differentiation, or apoptosis. Three aspects of extracellular matrix were extensively studied during the last decade: physical properties, spatial presentation of adhesive epitopes, and molecular complexity. Over 15 different parameters have been shown to influence stem cell choices. Physical aspects include stiffness (or elasticity), viscoelasticity, pore size, porosity, amplitude and frequency of static and dynamic deformations applied to the matrix. Spatial aspects include scaffold dimensionality (2D or 3D) and thickness; cell polarity; area, shape, and microscale topography of cell adhesion surface; epitope concentration, epitope clustering characteristics (number of epitopes per cluster, spacing between epitopes within cluster, spacing between separate clusters, cluster patterns, and level of disorder in epitope arrangement), and nanotopography. Biochemical characteristics of natural extracellular matrix molecules regard diversity and structural complexity of matrix molecules, affinity and specificity of epitope interaction with cell receptors, role of non-affinity domains, complexity of supramolecular organization, and co-signaling by growth factors or matrix epitopes. Synergy between several matrix aspects enables stem cells to retain their function in vivo and may be a key to generation of long-term, robust, and effective in vitro stem cell culture systems. PMID- 26351464 TI - Morphometric Analysis of Human Embryonic Stem Cell-Derived Ventricular Cardiomyocytes: Determining the Maturation State of a Population by Quantifying Parameters in Individual Cells. AB - Quantitative methods were established to determine the level of maturation of human embryonic stem cell-derived ventricular cardiomyocytes (hESC-vCMs) that were treated with different metabolic stimulants (i.e., isoproterenol and oleic acid) during early differentiation. Cells were double-immunolabeled with alpha actinin and COX IV antibodies, to label the myofibrils and mitochondria, respectively, after which images were acquired via confocal microscopy. In order to determine the extent of differentiation, image analysis protocols were then used to quantify cell shape and area, as well as the degree of myofibrillar organization and intercalation of mitochondria between the myofibrils within the cells. We demonstrated that oleic acid or isoproterenol alone, or a combination of the two, induced a more elongated hESC-vCM phenotype than the untreated controls. In addition, cells treated with isoproterenol alone exhibited a similar level of myofibrillar organization as the controls, but those treated with oleic acid with/without isoproterenol exhibited a more organized (parallel) orientation of myofibrils. The combined isoproterenol/oleic acid treatment also resulted in enhanced intercalation of mitochondria between the myofibrils. We suggest that these quantitative morphometric methods might serve as simple and effective tools that can be utilized in the determination of the level of structural maturation of hESC-vCMs. PMID- 26351465 TI - Intravenous Cardiac Stem Cell-Derived Exosomes Ameliorate Cardiac Dysfunction in Doxorubicin Induced Dilated Cardiomyopathy. AB - Despite the efficacy of cardiac stem cells (CSCs) for treatment of cardiomyopathies, there are many limitations to stem cell therapies. CSC-derived exosomes (CSC-XOs) have been shown to be responsible for a large portion of the regenerative effects of CSCs. Using a mouse model of doxorubicin induced dilated cardiomyopathy, we study the effects of systemic delivery of human CSC-XOs in mice. Mice receiving CSC-XOs showed improved heart function via echocardiography, as well as decreased apoptosis and fibrosis. In spite of using immunocompetent mice and human CSC-XOs, mice showed no adverse immune reaction. The use of CSC XOs holds promise for overcoming the limitations of stem cells and improving cardiac therapies. PMID- 26351466 TI - Noonan syndrome and Turner syndrome patients respond similarly to 4 years' growth hormone therapy: longitudinal analysis of growth-hormone-naive patients enrolled in the NordiNet(r) International Outcome Study and the ANSWER Program. AB - BACKGROUND: Turner syndrome (TS) and Noonan syndrome (NS) are distinct syndromes associated with short stature and other similar phenotypic features. We compared the responses to growth hormone (GH) therapy of TS and NS patients enrolled in the NordiNet(r) International Outcome Study (IOS) or the American Norditropin Studies: Web-Enabled Research (ANSWER) Program, which collect information on GH therapy in clinical practice. METHODS: Repeated-measures regression analysis was performed on change in height standard deviation score (HSDS) and target-height corrected HSDS, based on national normal references and treatment-naive disease specific references. Models were adjusted for baseline age and HSDS, and average GH dose. The study population was paediatric patients with TS and NS in the NordiNet(r) IOS and ANSWER Program. Longitudinal growth responses over 4 years were evaluated. RESULTS: In 30 NS patients (24 males; baseline age 8.39 +/- 3.45 years) and 294 TS patients (7.81 +/- 3.22 years), 4-year adjusted DeltaHSDS were +1.14 +/- 0.13 and +1.03 +/- 0.04, respectively (national references). Based on untreated, disease-specific references, 4-year adjusted DeltaHSDS for NS and TS were +1.48 +/- 0.10 and +1.79 +/- 0.04. The analyses showed a significant increase in HSDS over time for both NS and TS (P < 0.0001). DeltaHSDS in NS was higher with younger baseline age; DeltaHSDS in TS was higher for patients with younger baseline age and higher GH dose. CONCLUSIONS: NS and TS patients responded well and similarly over 4 years of GH treatment. PMID- 26351467 TI - Fibrogenesis: Mechanisms, Dynamics and Clinical Implications. PMID- 26351468 TI - Evaluation of Endoglin as an Angiogenesis Marker in Glioblastoma. AB - BACKGROUND AND OBJECTIVES: Angiogenesis is essential for growth and metastasis of solid malignancies. Tumor vessel count and expression of vascular endothelial growth factor (VEGF), a potent angiogenic factor, have been associated with prognosis. This study was designed to assess vessels density by using CD31 and CD105 (Endoglin) and their correlation with expression of VEGF and proliferative index (Ki67) in Glioblastoma multiforme (GBM). METHODS: We examined these parameters in GBM specimens from 50 adult patients; referred to Al-Zahra hospital Pathology Lab between 2001 to 2006.These patients did not receive pre-operative therapy. Paraffin-embedded tumor specimens were immunohistochemically stained for CD31, CD105 (Endoglin), VEGF and Ki67 (proliferation index) monoclonal antibodies. Microvessel density (MVD) was evaluated by immunostaining for CD31 and CD105.Then the results were compared between the two and also with VEGF receptors and Ki67 index. RESULTS: CD105-MVD was significantly higher in Glioblastoma compared with peritumoral normal (14.28 vs. 6.68: P=0.012). We did not find such difference for CD31. The mean of CD105-MVD was significantly higher than CD31-MVD in Glioblastoma tissue (P<0.001) although there was a significant positive relationship between them (Pearson's r=0.630 P<0.001).The VEGF scoring for tumoral tissue was 12 % (score:1), 46% (score:2) and 42% (score:3).For peritumoral normal tissue were 92% (score:1) and 8% (score:2) . So they reach to statistical significance (Chi Square, P = 0001). Both MVD of CD105 and CD31 have significant relationship with VEGF (P<0.001). CONCLUSION: We suggest that Endoglin can be used as a specific and sensitive marker for evaluation of angiogenesis in Glioblastoma. PMID- 26351469 TI - Reduction of Listeria monocytogenes and Bacillus cereus in Milk by Zinc Oxide Nanoparticles. AB - BACKGROUND & OBJECTIVES: Direct addition of antimicrobial materials to food during food processing is an effective method for controlling microbial contaminants of food and extending the shelf- life of food products. Objective of this research was to study the antimicrobial effect of zinc oxide (ZnO) nanoparticle and potential applications of ZnO nanoparticles in terms of controling two food-borne pathogens in milk. METHODS: Toxicity of different concentration (0, 0.5, 2, 5, and 10 mM) of ZnO nanoparticles on Listeria monocytogenes and Bacillus cereus was studied in culture media and milk. RESULTS: Among the mentiond concentrations, treatment of 10 mM of ZnO nanoparticle was the most effective one for L. monocytogenes and B. cereus inhibition, which completely inhibited the growth of L. monocytogenes and B. cereus in 24h. These data revealed concentration-dependency of the antibacterial activity of ZnO. Therefore, 5 mM and 10 mM ZnO were selected for further studies, which were performed in milk, since they demonstrated significant growth inhibition. ZnO NPs were more capable in terms of reducing the initial growth counts of all the above stated strains in milk. CONCLUSION: ZnO nanoparticles had an antimicrobial activity against L. monocytogenes and B. cereus in milk and the media. This work was a preliminary study that provided a starting point for determining whether the use of ZnO nanoparticles had the potential for being applied in food preservation or not. PMID- 26351470 TI - Comparison of Mast Cells Count in Odontogenic Cysts Using Histochemical Staining. AB - BACKGROUND & OBJECTIVES: Odontogenic cysts are among the most frequent destructive lesions of jaws which their pathogenesis and growth mechanism are not cleared. With respect to different roles of mast cells, they may play a role in the pathogenesis and growth of odontogenic cysts. The aim of present study was to evaluate mast cells in the most common odontogenic cyst. METHODS: Thirty paraffin embedded tissue blocks including 10 radicular cysts, 10 dentigerous cysts and 10 odontogenic keratocysts were used and 5 micron sections stained with toluidine blue and observed by light microscope under *400 magnification to evaluate mast cells within these cysts. For each case, 5 high-power field areas, selected from hot-spot areas, were considered and each area divided into 3 zones: intra epithelial zone, sub-epithelial zone and deep zone. RESULTS: Most of the studied cyst showed presence of mast cells. There was not any significant difference in mast cell count between studied cysts ( P -values > 0.05).With respect to intra epithelial, sub-epithelial and deep zones, there was not any significant difference between three studied cysts. There was not any significant difference between sub-epithelial zone and deep zone within each of these cysts. There was only significant difference between intra-epithelial zone and sub-epithelial zone within dentigerous cysts and odontogenic keratocysts ( P -value < 0.05). CONCLUSIONS: Prevalence of mast cells in fibrous wall of odontogenic cysts suggests their activity in these cysts. Mast cells may not be directly involved in the pathogenesis of odontogenic keratocysts. PMID- 26351471 TI - Comparative Study of Clinical Staging of Oral Submucous Fibrosis with Qualitative Analysis of Collagen Fibers Under Polarized Microscopy. AB - BACKGROUND & OBJECTIVES: Oral submucous fibrosis (OSMF) is a condition where excessive deposition of dense collagen fibers occurred in the connective tissue of oral mucosa. An alteration of collagen necessitates an in depth understanding of collagen in oral tissues as no breakthrough studies have been reported. T herefore the aim was to correlate the clinical, functional and histopathological staging and to analyze the polarization colors and thickness of the collagen fibers in different stages of OSMF using picrosirius red stain under polarizing microscopy so as to assess the severity of disease. METHODS: The study was conducted in the department of Oral Pathology and Microbiology at Padm. Dr. D. Y Patil Dental and Hospital, Navi Mumbai, India (2012-13). A sample size was of a total 40 subjects, of which 30 patients had OSMF, and 10 were in control group. Clinical, functional and histopathological staging were done depending upon definite criteria. Collagen fibers were analyzed for polarizing colors and thickness. Further clinical, functional and histopathological stages as well as qualitative parameters of collagen fibers were compared. RESULTS: The correlation between clinical and functional staging was not significant ( P >0.05) whereas the comparison of the functional staging with histopathological staging was more reliable ( P <0.01) as an indication to the severity of the disease rather than clinical staging. One-way ANOVA analysis showed highly significant correlation between functional staging and polarization colors and thickness of collagen fibers ( P <0.001). CONCLUSION: The qualitative change in the collagen fibers of OSMF patients using polarized microscopy would help to assess its role in diagnostic evaluation, to determine the prognosis of the disease as well as to provide useful predictive treatment modalities to them. PMID- 26351472 TI - Frequency of Group B Streptococcal Colonization in Pregnant Women Aged 35- 37 Weeks in Clinical Centers of Shahed University, Tehran, Iran. AB - BACKGROUND & OBJECTIVES: One of the important infectious factors in pregnant mothers and newborns is Group B Streptococcus (GBS). There is no perfect report about prevalence of GBS in Iran and in the case of preterm rupture of amniotic membrane or preterm labor all patients are treated by antibiotics without culture so this has led to adverse taking antibiotics and drug resistance. The present study is intended to determine the frequency of colonization of GBS in the pregnant mother (35-37 weeks), referred to medical centers of Shahed University. METHODS: Overall, 210 pregnant women (35-37 weeks), referred to medical center of Shahed University, Tehran, Iran were selected as sample group and after filling out the questionnaires about demographic data and midwifery status and the related information of post- partum, the rectovaginal culture was done for them. RESULTS: Among 210 samples, 7 (3.3%) included positive culture in terms of GBS colonization while all these cases were sensitive to penicillin, ampicillin, cephalothin, nitrofurantoin, and all of the samples were resistant against tetracycline and contrimoxazole. There was no relationship among age, job, education, number of pregnancy, blood pressure background, diabetes and preterm childbirth with positive culture. Similarly, because of limited number of positive cases it was not possible to examine the relationship among GBS colonization and infection in mother and newborn. CONCLUSION: There was a low frequency in GBS colonization in the studied hospitals and the study inside the country also confirms this finding. PMID- 26351473 TI - Prognostic Value of Lymph Node Ratio in Comparison to Lymph Node Metastases in Stage III Colon Cancer. AB - BACKGROUND & OBJECTIVES: Colon cancer is currently of high incidence and mortality rate. Identifying the factors influencing its prognosis can be very beneficial to its clinical treatment. Recent studies have shown that lymph nodes ratio can be considered as an important prognostic factor. The aim of the present study is to investigate the effect of this factor on the prognosis of the patients presenting with stage III colon cancer and to compare the result with the effect of lymph node stage on their prognosis. MATERIALS: This cross sectional study was carried out on 66 patients of stage III colon cancer, who met the study inclusion criteria. Patients were categorized into four groups based on Kaplan-Meier plots: LNR1 0-12%, LNR2 13-40%, LNR3 41-84% and LNR4 85-100%. Survival was estimated by Kaplan-Meier method, and differences analyzed by Log rank test. A Cox proportional hazards model was used for multivariate analysis. RESULTS: Lymph nodes ratio was a significantly variable both in overall survival ( P <0.0001) and in disease-free survival ( P =0.009). Lymph node stage was significant in overall survival ( P =0.008) but not in disease-free survival ( P =0.05). Multivariable analysis of overall survival showed lymph nodes ratio as the only independent prognostic factor. CONCLUSION: Lymph node ratio is a more accurate prognostic factor than lymph node stage in overall survival and, in particular, in disease-free survival in patients with stage III colon cancer. PMID- 26351474 TI - Comparison of Serum Autoantibodies to Desmogleins I, III in Patients with Oral Lichen Planus and Healthy Controls. AB - BACKGROUND & OBJECTIVE: Lichen planus is a mucocutaneous disease which is relatively common and in 30-70% of patients, mucosal lesions can be seen and known as a precancerous lesion but its etiology is not completely understood. Desmogleins I and III are the main desmosomal transmembrane proteins. These proteins have been identified as the autoantigen of the autoimmune disease. The aim of this study was evaluation of serum autoantibodies against desmogleins Iota, IotaIotaIota in oral lichen planus . METHODS: We attempted to determine the etiology of this disease with evaluation of these serum factors. Thirty-five patients with oral lichen planus and 35 healthy controls were recruited and tested for serum autoantibodies against desmogleins Iota, IotaIotaIota and indirect immunofluorescence also performed. Data were analyzed by statistical analytical methods (Independent sample t -test) with using the SPSS.15 software. RESULTS: Serum autoantibody against desmoglein Iota had no significant difference in the two groups ( P =0.31 ) but significant increase in serum autoantibody to desmoglein IotaIotaIota was found in patients with oral lichen planus ( P =0.00) . CONCLUSION: It seems that autoantibody against desmoglein III has a significant role in the pathogenesis of oral lichen planus. PMID- 26351475 TI - Lack of Association between Interleukin-10 Gene Promoter Polymorphisms with HIV Susceptibility and Progression to AIDS. AB - BACKGROUND: Interleukin (IL)-10 is an important anti-inflammatory and immunomodulatory cytokine. Some authors believe that single nucleotide polymorphisms (SNP) in the promoter region of the IL-10 gene have been associated with susceptibility to HIV infection and progression to AIDS, but its role is not clearly defined yet. The present study was undertaken to evaluate the association between HIV infection susceptibility and progression with SNP in the promoter region of the IL-10 gene. METHODS: This study was carried out in 70 HIV infected patients (39 treatment naive and 31 under treatment) and 31 matched healthy controls. The biallelic polymorphisms in the IL-10 gene promoter (-592 ,-1082) were analyzed by polymerase chain reaction and direct sequencing. RESULTS: At position -1082, G/A was the most common genotype and A was the most prevalent allele and at position -592, A/C was the most prevalent genotype and -592 C was the most common allele in HIV positive patients; although there was not any significant difference between cases and controls regarding genotypes and alleles of these regions. CONCLUSION: Our study showed that genetic polymorphisms of IL 10 promoter region may not associate with HIV infection outcome and the lack of this association suggests that other genes may influence on HIV infection course. PMID- 26351476 TI - Reactive Nodular Fibrous Pseudotumor Presenting as a Huge Intra abdominal Mass after Abdominal Surgery: a Case Report. PMID- 26351477 TI - A Rare Case of Cutaneous Leishmaniasis Presenting as Rhinophyma. PMID- 26351478 TI - Recurrent Glandular Odontogenic Cyst of Maxilla- A Case Report. PMID- 26351479 TI - Unilateral Tuberculous Epididymo- Orchitis with Scrotal Fistula: a Case Report. PMID- 26351480 TI - Coexistence of Pericardialand Hepatic Hemangiomas. PMID- 26351481 TI - Polymerase Chain Reaction for the Diagnosis of Tuberculosis. PMID- 26351482 TI - The Spindle Cell Neoplasms of the Oral Cavity. AB - Spindle cell neoplasms are defined as neoplasms that consist of spindle-shaped cells in the histopathology. Spindle cell neoplasms can affect the oral cavity. In the oral cavity, the origin of the spindle cell neoplasms may be traced to epithelial, mesenchymal and odontogenic components. This article aims to review the spindle cell neoplasms of the oral cavity with emphasis on histopathology. PMID- 26351483 TI - The Effects of Cyclin D1 and Bcl-2 Expression on Aggressive Behavior in Basal Cell and Basosquamous Carcinoma. AB - BACKGROUND AND OBJECTIVE: Clinical behavior of basal cell carcinoma (BCC) is known to be different according to histological growth pattern and basosquamous cell carcinomas (BSC) are known with their aggressive behavior and metastatic capacity. In this study, we evaluated bcl-2 and cyclin D1 expressions in BCC and BSC cases comparatively, to explore their predictive value on the aggressive behavior of these tumors. METHODS: One hundred tumors belong to 92 patients diagnosed as basal cell carcinoma and basosquamous carcinoma were studied. Basal cell carcinomas were classified as aggressive and non-aggressive types according to growth pattern. Number of Cyclin D1 and bcl-2 positive cells in immunohistochemically stained serial sections were scored as low (0-1 +) and high (2 and 3+) in all tumors. RESULTS: A statistically significant difference was found between non-aggressive (nodular type) and aggressive types (micronodular, infiltrative types and BSC) for these markers ( P <0.005). Cyclin D1 was higher in the aggressive group, while bcl-2 was lower in the aggressive group compared to the non-aggressive group. CONCLUSION: Higher Cyclin D1 and lower bcl-2 scores was correlated with aggressive tumor types and these results could be used as markers to predict aggressive behavior in BCC and BSCs. PMID- 26351484 TI - Frequency of Human Papillomavirus Genotypes 6, 11, 16, 18 And 31 in Paraffin Embedded Tissue Samples of Invasive Breast Carcinoma, North- East of Iran. AB - BACKGROUND &OBJECTIVE: Breast cancer is the most common female malignancy. Detection of DNA of human papillomaviruses (HPVs) in breast carcinomas suggests that the virus may play a role in the pathogenesis of this disease. The aim of this study was to evaluate the frequency of HPVs genotypes 6, 11, 16, 18 and 31 in paraffin-embedded tissue samples of invasive breast carcinomas. METHODS: Three hundred and twenty six paraffin-embedded tissue samples of breast cancer were studied. PCR was performed using specific primers for HPV genotypes. RESULTS: Of total 206 (63.2%) samples positive for Beta-globin gene, 54 (26.2%) were HPV positive and 152 (73.8%) were negative for HPV. Distribution of HPV genotypes were as follows: 19 (25.7%) were positive for genotype 11, 5 (6.8%) were positive for genotype 6; and 2 cases (2.7%) were positive for both genotypes 6 and 11. Samples were also screened for HPV genotypes 16, 18 and 31 but none was positive. CONCLUSION: The current study confirmed the association of HPV and breast cancer. However, all samples were negative for high-risk HPV types 16, 18 and 31. PMID- 26351485 TI - Detection of the Klebsiella pneumoniae carbapenemase (KPC) in K. pneumoniae Isolated from the Clinical Samples by the Phenotypic and Genotypic Methods. AB - BACKGROUND AND OBJECTIVE: The production of carbapenemases especially Klebsiella pneumoniae carbapenemase (KPC) is the most important mechanism of enzymatic resistance in isolated Enterobacteriaceae such as K. pneumoniae . The purpose of this study was detected of the carbapenemase producer K. pneumoniae strains with phenotypic and genotypic methods. METHOD: Out of 800 strains, 270 K. pneumoniae strains (33.7%), were obtained. Antibiotic susceptibility test was performed by disk diffusion method in accordance with CLSI guidelines. Carbapenem resistant strains were identified by the Modified Hodge Test based on CLSI instruction and PCR for surveying the presence of bla -KPC gene. RESULTS: A total 270 K. pneumoniae strains were collected. Antibiotic susceptibility test results showed the highest and lowest resistance was related to piperacillin (60.6%) and carbapenems (14.6%) respectively. 80.5% (33 of 41) isolates were positive by MHT, but all of them (100%) were negative for amplification of the bla -KPC gene in the PCR method. CONCLUSION: The MHT was an appropriate method for approving carbapenemase production. Moreover, a laboratory could accept the carbapenemase production with PCR method for the bla-KPC gene, which has the additional profit of validating which KPC is present. PMID- 26351486 TI - Streptozotocin Induced Acute Clinical Effects in Rabbits (Oryctolagus cuniculus). AB - BACKGROUND & OBJECTIVES: Streptozotocin (STZ) is used for induction of Type-1 diabetes mellitus in animal models. Its beta-cytotoxic action results in sudden release of insulin leading to severe hypoglycaemia and even mortality. However, its sensitivity varies with species. Present investigation was aimed at studying STZ induced acute clinical effects in rabbits. METHODS: Streptozotocin @ 65 mg/kg b.w. was administered to thirteen New Zealand White rabbits, 1-1.5 kg body weight, as single intravenous dose in 1mL citrate buffer, pH 4.6. Blood glucose levels were recorded before drug administration and then at 20 min, 1h, and hourly up to 9 hours post-treatment followed by intravenous and oral glucose therapy. Clinical signs were noted. RESULTS: STZ caused immediate hyperglycaemia up to 4 hours, and then progressively severe hypoglycaemia up to 9 hours. Hypoglycaemia caused characteristic behavioural alterations including lethargy, dullness, sitting quietly but appearing alert, followed by aesthesia and then muscular weakness with characteristic postural changes starting from drooping of head and torticollis, Rabbits recovered following glucose therapy. Marked individual variations in response vis-a-vis onset and severity of glycaemic changes were observed. CONCLUSION: STZ induced a characteristic multiphasic immediate response in rabbits similar to one reported in other rodents. Behavioural changes were characteristic of hypoglycaemia warranting early management in order to avoid fatalities. PMID- 26351487 TI - The Impact of Smoking on Gingiva: a Histopathological Study. AB - BACKGROUND AND OBJECTIVE: Smoking can be associated with the decreasing gingival blood flow and epithelial changes. The aim of this study was to evaluate the histopathological changes of gingival epithelium and connective tissue in smokers . METHODS: The study was case-control. Sixty male patients ( 28 smokers and 32 non smokers) suffering chronic periodontitis were participated in the study . Periodontal parameters consisting the gingival (GI) and periodontal (PI) indexes were registered. Tissue samples were taken during flap surgery. The hemotoxylin and eosin stained slides were assessed for blood vessel density, inflammatory cells infiltration and epithelial changes. The histopathological findings were compared between smokers and nonsmokers. Data analyzed using t -test and chi square tests. RESULTS: Smokers had lower GI (1.35 +/- 0.48) and higher PI (2.87+/ 0.68) than nonsmokers (2.72 +/-0.31 and 1.87+/-0.25, respectively). The mean count of blood vessels with <= 0.5u diameter was 18.78+/-10.06 and 5.90+/-2.93 in smokers, nonsmokers, respectively. The mean inflammatory cells infiltration in smokers, and nonsmokers were 0.89+/-1.03 and 70+/-0.46 that showed significant difference between two groups ( P = 0.001, SD=1.21). The difference of epithelial hyperkeratosis, atrophy and acanthosis was not different in smokers and nonsmokers. Loss of normal epithelium pattern comprising of bulbous rete ridges, loss of polarity and increased parabasal cells was seen in 23(82.14%) of smokers and 2(6.25%) of nonsmokers. CONCLUSION: Despite the normal appearance of gingiva in smokers, smoking increasing the epithelial changes resemble to early phases of dysplasia and decreasing inflammatory reaction. PMID- 26351488 TI - Correlation of ER, PR and HER-2/Neu with other Prognostic Factors in Infiltrating Ductal Carcinoma of Breast. AB - BACKGROUND AND OBJECTIVES: Breast cancer is the most common malignancy among women in the world. The aim of this study was to assess estrogen receptor (ER), progesterone receptor (PR) and HER-2/neu of infiltrating ductal carcinoma (IDC) with tumor size, histologic grade, lymph node metastasis and age. METHODS: This study was carried out on 300 tissue blocks of patients with IDC who underwent mastectomy from 2007 to 2011 in Shahid Beheshti Hospital, affiliated to Babol University of Medical Sciences, Babol, Iran. Data including age, tumor size, and histologic grade and lymph node status retrieved from pathology department. RESULT: The mean age of the patients was 40.2+/-2.3 (ranged 19-82 years). ER and PR were positively correlated with each other ( P = 0.001) and they inversely correlated with HER-2/neu ( P =0.001). We observed correlation between ER and PR expression and low histologic grade ( P = 0.001) and HER-2/neu expression and high histologic grade ( P = 0.003). There was correlation between HER-2/neu expression and lymph node involvement ( P =0.03). None of these makers showed correlation with age and tumor size ( P > 0.05). CONCLUSION: Our findings indicate the importance of ER, PR and HER-2/neu expression as prognostic factors for therapeutic decision. PMID- 26351489 TI - Retroperitoneal Anaplastic Neuroblastoma in a 3-Year-Old Female: A Rare Case Report. PMID- 26351490 TI - Mucinous Carcinoma of the Breast with Neuroendocrine Differentiation. PMID- 26351491 TI - Enchondroma of the Skull Base in a Case of Ollier's Syndrome. PMID- 26351492 TI - Leiomyoma of Scrotum: a Rare Case Report. PMID- 26351493 TI - Incidentally Detected Blue Nevus of Endocervix: a Case Report. PMID- 26351494 TI - Are Osteopontin and Ki67 Expressions Different in Various Histologic Grades of Meningioma? An Iranian Experience. AB - BACKGROUND: Meningioma is among the most common slow growing central nervous neoplasms, which recurs locally despite the benign histologic features. The aim of this study was to evaluate osteopontin and ki67 expressions in different histologic grades of meningioma in a group of Iranian people. METHODS: In this cross-sectional study, first, the paraffin blocks with the definite pathological diagnosis of meningioma in 70 patients were cut by microtome, in 4-5 micron sizes and stained for immunohistochemical markers of osteopontin and ki67. Then, all samples were evaluated for positive immunoreactivity and contributing factors. RESULTS: Among 70 pateints studied, the mean for the Ki67 level was 8.6+/-12.3 and the mean for the osteopontinm IHC score was 45.2+/-77.9. There was a high correlation between markers, tumor recurrence and grade (P<0.001). In addition, there was a significant direct correlation between ki67 and osteopontin levels (P<0.001, r=0.760). In other words, as OPN and ki67 expressions increased, the chance of tumor recurrence increased. CONCLUSION: ki67 and osteopontin expressions in patients with meningioma can be used as good prognostic markers for tumor recurrence and for distinguishing the grade of meningiomas. PMID- 26351495 TI - The Microbial Surface Components Recognizing Adhesive Matrix Molecules (MSCRAMMs) Genes among Clinical Isolates of Staphylococcus aureus from Hospitalized Children. AB - BACKGROUND: Isolates of Staphylococcus aureus express a myriad of adhesive surface proteins that play important role in colonization of the bacteria on nasal and skin surfaces, beginning the process of pathogenesis. The aim of this study was to screen several of the Microbial Surface Components Recognizing Adhesive Matrix Molecules (MSCRAMMs) genes among the isolate of S. aureus from hospitalized children. METHODS: A total of 22 S. aureus isolates were collected from hospitalized children in Tehran from 2012 to 2013. Detection of the mecA and several adhesive surface proteins genes including clfA, B (encoding clumping factors A, B); fnbA, B (encoding finronectin binding proteins A, B); fib (encoding fibrinogen binding protein); eno (encoding laminin binding protein); cna (encoding collagen binding protein); ebps (encoding elastin binding protein) and bbp (encoding bone sialo-protein binding protein), was performed by PCR. RESULTS: The clfAB genes were detected among all the isolates. The prevalence of fnbA, fnbB, fib, eno, cna, ebps and bbp was 63%, 6%, 50%, 59%, 82%, 63%, 9% and 0%, respectively. CONCLUSION: The high prevalence of these genes is important for future plans in vaccine designation. MRSA and MSSA isolates similarly can produce adhesive surface proteins for colonization. PMID- 26351496 TI - Detection of Multidrug Resistant (MDR) and Extremely Drug Resistant (XDR) P. Aeruginosa Isolated from Patients in Tehran, Iran. AB - BACKGROUND: This study was done to detect multidrug resistant (MDR) and extremely drug resistant (XDR) of Pseudomonas aeruginosa among strains isolated from patients in Tehran, Iran, due to importance of these phenotypes in treatment of human infections. METHODS: Eighty eight P. aeruginosa were isolated from patients in Tehran, Iran, and identified by routine methods and PCR for oprL gene. Their antimicrobial susceptibility to 16 antimicrobial agents from 7 antimicrobial categories (aminoglycosides, carbapenems, cephalosporins, fluoroquinolones, penicillins/beta-lactamase inhibitors, monobactams, polymyxins) were determined by disk diffusion method, according to recommendation of Clinical and Laboratory Standards Institute. Characterization of P. aeruginosa isolates as MDR and XDR was done according to standardized international terminology presented by European Centre for Disease Prevention and Control as well as the Centers for Disease Control and Prevention in 2011. MDR was defined as acquired non susceptibility to at least one agent in >=3 antimicrobial categories and XDR was defined as non-susceptibility to at least one agent in >=6 antimicrobial categories. RESULTS: The rates of susceptibility to antimicrobials were as follows: gentamicin 27.3%, tobramycin 54.5%, amikacin 56.8%, netilmicin 36.4%, imipenem 55.7%, meropenem 55.7%, doripenem 60.2%, ceftazidime 63.6%, cefepime 56.8%, ciprofloxacin 59.1%, levofloxacin 60.2%, ticarcillin-clavulanic acid 37.5%, piperacillin-tazobactam 63.6%, aztreonam 43.2%, colistin 90.9%, polymyxin 95.5%. Altogether, 48 (54.5%) and 29 (33%) isolates were characterized as MDR and XDR, respectively. DISCUSSION: The high frequency of antibiotic resistance in clinical isolates of P. aeruginosa in Iran makes epidemiological surveillance of susceptibility of this bacterium more essential for the best selection of empirical antibiotics. PMID- 26351497 TI - Protective Effects of Hydrocortisone, Vitamin C and E Alone or in Combination against Renal Ischemia-Reperfusion Injury in Rat. AB - BACKGROUND: Renal ischemia reperfusion injury may occur in a variety of clinical situations, following a transient drop in total or regional blood flow to the kidney. This study was performed to investigate the protective effects of different antioxidants such as vitamin C, vitamin E, hydrocortisone and combination of these agents against experimental renal ischemia-reperfusion injury. METHOD: Thirty male rats were divided into six groups. Group Sham, Group I/R: (45 min of ischemia followed by 1h of reperfusion), Group I/R+Vit C: (50 mg/kg Vit C, IV, immediately after reperfusion), Group I/R+Vit E: (20 mg/kg Vit E, IM, 15 min before reperfusion), Group I/R+Hydrocortisone: (50 mg/kg, IV, immediately after reperfusion), and Group Combination: Ischemia-reperfusion plus combination of Vit C, E and hydrocortisone. After the experiments, the left kidney was removed and the tissues were processed for histopathological examination. RESULT: Severe injuries such as necrosis of tubules, atrophy of glomerulus, and hemorrhage were observed in group I/R. Histological scores indicating tissue injury significantly decreased in all treatment groups compared to the group I/R. The renal tissue in group treatment was preserved in comparison with the group I/R. Comparison between the treatment groups showed that group combination was more effective and group vit E was less effective in protecting of renal tissue against I/R injuries. CONCLUSION: The results demonstrated simultaneous administration of combination of Vit C, E and hydrocortisone before reperfusion of blood flow to the ischemic tissue could show a synergy against deleterious effects of I/R injuries in kidney. PMID- 26351498 TI - Renal Tumours in Adults with Correlation between Fuhrman Grading and Proliferative Marker. AB - BACKGROUND: Definite data regarding the incidence and distribution of renal tumours in eastern India is not known. For better management, as it is essential to identify patients with poor prognosis, prognostic factors like stage, nuclear grade and their relationship to molecular markers are also unclear in this region. The purpose of our study was to assess the spectrum of adult renal tumours with respect to age and sex and to correlate Fuhrman nuclear grading with Ki-67 labeling index in a tertiary care hospital in eastern India. METHODS: All adult patients with kidney tumour referred to our hospital who were preoperatively diagnosed and undergone surgical resection were included. Distribution of histological subtypes of kidney tumours according to age and sex were done by Hematoxylin and Eosin stain. Fuhrman grading, performed by ocular morphometry and derivation of Ki-67 labeling index (LI), were done in malignant cases only. Correlation of Fuhrman grading and KI-67 LI were done individually. RESULTS: Among total 36 cases, 3 were benign and 33 were malignant. Among the malignant cases: Fifteen, twelve, four and two cases were of Fuhrman grade I, II, III, IV with mean Ki67 labeling index of 6.5, 18.2,44 and 76 respectively. Statistical correlation between mean Ki-67 LI and Fuhrman grading revealed significant correlation between Grade I and II, II and III and combined Grade I,II and III,IV tumours. CONCLUSION: Malignant Kidney tumours, especially, grade I RCC were commonest tumour. Fuhrman grading correlated well with Ki-67 labeling index. A 2-tier system for grading is proposed for better correlation with proliferation. PMID- 26351499 TI - A Five Years Study of Tuberculous Meningitis in Iran. AB - BACKGROUND: Tuberculous meningitis (TBM) is a severe form of extra pulmonary tuberculosis with high mortality and morbidity rate in all age group patients specific in adults and children. The incidence and prevalence are not exactly known in Iran. In this study, we tried to evaluate the role of rapid diagnosis and to find out the highest risk group patients. METHODS: Totally, 1783-suspected patients with tuberculous meningitis whose CSF specimens were admitted at Noor Pathobiology Laboratory, Tehran, Iran were enrolled in this study from January 2009 until December 2013. All specimens were checked for MTB by direct examination, culture and PCR tests, and for the adenosine deaminase (ADA). RESULTS: Confirmed positive cases were aged from 13 to 82 yr old with mean age 46.63 yr (SD+/-18.84). The number of diagnosed positive MTB was different by the 3 applied protocol, 64 by PCR, 28 by culture and 33 by direct examination. Considering the result of PCR protocol the TBM was approved in 64 patients with rate of 3.59%. Two patients had other infection as well, one 56 years old with VZV and the other patient who was HIV positive was 27 years old. Increased ADA titer higher than cutoff was relevant with other results of positive samples except in two cases. CONCLUSION: Analysis of the results proved adults are more at risk for tuberculous meningitis than children in Iran are. It is also confirmed PCR method provide the most efficient, rapid and reliable results for these patients who are at the critical situations. PMID- 26351500 TI - The Diagnostic Accuracy of Frozen Section Compared to Permanent Section: A Single Center Study in Iran. AB - BACKGROUND: The diagnostic accuracy of frozen section as an important source of information in surgical pathology is important not only in the management of surgical patients but also as a measure of quality control in surgical pathology. In this study, we evaluated the diagnostic accuracy of frozen sections over a 6 year period in a teaching hospital in Iran. METHODS: We retrospectively reviewed frozen sections performed in the Pathology Department of Taleghani Hospital (Shahid Beheshti University of Medical Sciences), Tehran, Iran from 2007 to 2013. The results were compared to the permanent sections to evaluate diagnostic accuracy, sensitivity and specificity, of frozen section test. Discordant cases were reassessed to find the reasons for discrepancy. RESULTS: A total of 306 frozen section specimens from 176 surgical cases were evaluated. In eleven specimens (3.59%) the diagnoses were deferred. Of the remaining 295 specimens, 6 (2.03%) were discordant and 289 (97.96%) were concordant to permanent diagnoses. Specimens were primarily from the head & neck, thyroid, ovary, parathyroid and lymph nodes. The overall sensitivity, specificity, positive predictive value and negative predictive value of the frozen section compared to permanent section (as gold standard) were 92.95%, 99.55%, 98.50% and 97.80% respectively. Of the 6 discordant diagnoses, two (33.3%) were due to sampling error and four (66.6%) were due to interpretative errors. CONCLUSION: Frozen section is an accurate and valuable test and can be relied on in surgical managements. The results of this study also confirm that the accuracy of frozen section diagnosis in our institution compares well with internationally published rates. PMID- 26351501 TI - Extensive Focal Epithelial Hyperplasia: A Case Report. AB - Focal epithelial hyperplasia (FEH) or Heck's disease is a rare viral infection of the oral mucosa caused by human papilloma virus especially subtypes 13 or 32. The frequency of this disease varies widely from one geographic region and ethnic groups to another. This paper reports an Iranian case of extensive focal epithelial hyperplasia. A 35-year-old man with FEH is described, in whom the lesions had persisted for more than 25 years. The lesion was diagnosed according to both clinical and histopathological features. Dental practitioner should be aware of these types of lesions and histopathological examination together and a careful clinical observation should be carried out for a definitive diagnosis. PMID- 26351502 TI - Gastric Calcifying Fibrous Tumor Resembling Gastrointestinal Stromal Tumor: A Case Report. AB - Calcifying fibrous tumor (CFT) is a rare mesenchymal tumor, affecting children and young adults with a predilection for the soft tissue and the abdominal cavity. CFT of the tubular gastrointestinal tract is very rare with less than 20 cases of gastric CFTs reported in English literature. This benign hypocellular fibrosclerotic calcifying lesion can resemble other spindle cell tumors particularly sclerosing gastrointestinal stromal tumor of the stomach. Differentiating between these lesions is particularly important for prognostic and therapeutic purposes. Herein a case of gastric calcifying fibrous tumor incidentally detected during bariatric surgery in a 27-year-old woman is described, with a discussion on its clinicopathological features and differential diagnoses. PMID- 26351503 TI - Cystic Hygroma in an Adult Male: A Diagnostic Challenge. AB - Cystic Hygroma is a well-recognized lesion in paediatric patients but it is very rare in adults. We report here a case of Cervical Cystic Hygroma in a 45 yr old male. The reasons to present this case are 1) Its rarity in adults 2) Unusual age of presentation 3) Simulates various benign and malignant lesions at this site 4) Is a diagnostic challenge and 5) Role of histology for definitive postoperative diagnosis. PMID- 26351504 TI - Giant Cell Fibroma of the Buccal Mucosa with Laser Excision: Report of Unusual Case. AB - Giant Cell Fibroma (GCF) was described as a new entity of fibrous hyperplastic soft tissue. It seems that stimulus from an unexplained origin can have a role in its etiology. Histopathologically GCF is consisted of multinucleated fibroblasts that have oval shape nuclei within the eosinophilic cytoplasm. Surgical excision is the treatment of choice and recurrence is very rare. Here we report a case of relatively large GCF in a 54-year-old man. Gingiva is the common location of GCF. As in our case, it may be mistaken as irritation fibroma especially if it is on the buccal mucosa, the most common location for fibroma. Correct diagnosis is based on biopsy and clinical examination to see surface texture roughness. To minimize bleeding because of its large size an excisional biopsy with Diod laser was performed under local anesthesia for this patient. PMID- 26351505 TI - The Adverse Effects of Pregnancies Complicated by Hemoglobin H (HBH) Disease. AB - Hemoglobin (Hb) H disease is a moderate form of alpha- thalassemia resulting from various genetic defects. HbH disease is not necessarily a benign disorder as has been generally thought. We present hereby a 25- year-old Iranian pregnant woman whom referred to our hospital for blood transfusion. She exhibited the clinical and hematological manifestation of HbH disease. Her father carries a common alpha thalassemia deletion while her mother was normal in the hematological profile. The object of this report was to provide information about pregnancies affected by HbH disease. PMID- 26351506 TI - Laryngeal Paraganglioma: A Diagnostic Challenge. AB - Paragangliomas are neoplasms of neural crest origin. In the head and neck, they uncommonly involve the larynx. The distinction between paragangliomas and other neuroendocrine tumors can be difficult. Precise diagnosis is important in order to optimize patient treatment. Diagnosis relies mostly on histopathologic examination followed by immunohistochemistry. Here we report a 77-year-old woman with laryngeal paraganglioma that initially misdiagnosed as laryngeal carcinoid tumor. PMID- 26351507 TI - Diarrhea Can Be an Important Clinical Presentation of 2014 Western Africa Ebola Virus Infection. PMID- 26351508 TI - Allium sativum L. Improves Visual Memory and Attention in Healthy Human Volunteers. AB - Studies have shown that Allium sativum L. (AS) protects amyloid-beta peptide induced apoptosis, prevents oxidative insults to neurons and synapses, and thus prevent Alzheimer's disease progression in experimental animals. However, there is no experimental evidence in human regarding its putative role in memory and cognition. We have studied the effect of AS consumption by healthy human volunteers on visual memory, verbal memory, attention, and executive function in comparison to control subjects taking placebo. The study was conducted over five weeks and twenty volunteers of both genders were recruited and divided randomly into two groups: A (AS) and B (placebo). Both groups participated in the 6 computerized neuropsychological tests of the Cambridge Neuropsychological Test Automated Battery (CANTAB) twice: at the beginning and after five weeks of the study. We found statistically significant difference (p < 0.05) in several parameters of visual memory and attention due to AS ingestion. We also found statistically nonsignificant (p > 0.05) beneficial effects on verbal memory and executive function within a short period of time among the volunteers. Study for a longer period of time with patients suffering from neurodegenerative diseases might yield more relevant results regarding the potential therapeutic role of AS. PMID- 26351509 TI - Studies on the Antifatigue Activities of Cordyceps militaris Fruit Body Extract in Mouse Model. AB - Cordyceps militaris has been used extensively as a crude drug and a folk tonic food in East Asia due to its various pharmacological activities. Our study aims to investigate the effect of Cordyceps militaris fruit body extract (CM) on antifatigue in mouse model. Two week CM administration significantly delayed fatigue phenomenon which is confirmed via rotating rod test, forced swimming test and forced running test. Compared to nontreated mouse, CM administration increased ATP levels and antioxidative enzymes activity and reduced the levels of lactic acid, lactic dehydrogenase, malondialdehyde, and reactive oxygen species. Further data suggests that CM-induced fatigue recovery is mainly through activating 5'-AMP-activated protein kinase (AMPK) and protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathways and regulating serum hormone level. Moreover, CM-enhanced the phosphorylation of AMPK contributes to its antioxidant effect. Our data provides experimental evidence in supporting clinical use of CM as an effective agent against fatigue. PMID- 26351510 TI - Ear Acupuncture Therapy for Masticatory Myofascial and Temporomandibular Pain: A Controlled Clinical Trial. AB - Ear acupuncture works by reducing painful sensations with analgesic effect through microsystem therapy and has been demonstrated to be as effective as conventional therapies in the control of facial pain. This clinical trial aimed to evaluate the adjuvant action of auricular acupuncture through an observation of the evolution of temporomandibular and masticatory myofascial symptoms in two groups defined by the therapies elected: auricular acupuncture associated with occlusal splint (study) and the use of the occlusal splint plate alone (control). We have selected 20 patients, who were randomly allocated into two groups of ten individuals. Symptoms were evaluated in five different moments, every seven days. We analyzed the orofacial muscle and joint palpation in order to measure the intensity of the experienced pain. Both groups showed a statistically significant decrease in muscle and joint symptoms (p < 0.05). However, comparisons between the groups showed an expressive and significant reduction of symptomatology in the study group (p < 0.05) already on the first week of therapy. According to the results, to the methodological criteria developed and statistical analysis applied, the conclusion is that auricular acupuncture therapy has synergistic action on conventional occlusal splint treatment. It was demonstrated to be effective in the reduction of symptoms in the short term. PMID- 26351511 TI - Berberine Regulated Lipid Metabolism in the Presence of C75, Compound C, and TOFA in Breast Cancer Cell Line MCF-7. AB - Berberine interfering with cancer reprogramming metabolism was confirmed in our previous study. Lipid metabolism and mitochondrial function were also the core parts in reprogramming metabolism. In the presence of some energy-related inhibitors, including C75, compound C, and TOFA, the discrete roles of berberine in lipid metabolism and mitochondrial function were elucidated. An altered lipid metabolism induced by berberine was observed under the inhibition of FASN, AMPK, and ACC in breast cancer cell MCF-7. And the reversion of berberine-induced lipid suppression indicated that ACC inhibition might be involved in that process instead of FASN inhibition. A robust apoptosis induced by berberine even under the inhibition of AMPK and lipid synthesis was also indicated. Finally, mitochondrial function regulation under the inhibition of AMPK and ACC might be in an ACL-independent manner. Undoubtedly, the detailed mechanisms of berberine interfering with lipid metabolism and mitochondrial function combined with energy related inhibitors need further investigation, including the potential compensatory mechanisms for ATP production and the upregulation of ACL. PMID- 26351512 TI - Auraptene, a Major Compound of Supercritical Fluid Extract of Phalsak (Citrus Hassaku Hort ex Tanaka), Induces Apoptosis through the Suppression of mTOR Pathways in Human Gastric Cancer SNU-1 Cells. AB - The supercritical extraction method is a widely used process to obtain volatile and nonvolatile compounds by avoiding thermal degradation and solvent residue in the extracts. In search of phytochemicals with potential therapeutic application in gastric cancer, the supercritical fluid extract (SFE) of phalsak (Citrus hassaku Hort ex Tanaka) fruits was analyzed by gas chromatography-mass spectrometry (GC-MS). Compositional analysis in comparison with the antiproliferative activities of peel and flesh suggested auraptene as the most prominent anticancer compound against gastric cancer cells. SNU-1 cells were the most susceptible to auraptene-induced toxicity among the tested gastric cancer cell lines. Auraptene induced the death of SNU-1 cells through apoptosis, as evidenced by the increased cell population in the sub-G1 phase, the appearance of fragmented nuclei, the proteolytic cleavage of caspase-3 and poly(ADP-ribose) polymerase (PARP) protein, and depolarization of the mitochondrial membrane. Interestingly, auraptene induces an increase in the phosphorylation of Akt, which is reminiscent of the effect of rapamycin, the mTOR inhibitor that triggers a negative feedback loop on Akt/mTOR pathway. Taken together, these findings provide valuable insights into the anticancer effects of the SFE of the phalsak peel by revealing that auraptene, the major compound of it, induced apoptosis in accompanied with the inhibition of mTOR in SNU-1 cells. PMID- 26351513 TI - Antioxidant and Anticholinesterase Potential of Six Thymus Species. AB - The present study aimed to evaluate antioxidant and acetylcholinesterase (AChE) inhibitory activities of the ethanolic extracts of six selected Thymus species growing in Croatia (T. longicaulis, T. praecox subsp. polytrichus, T. pulegioides, T. serpyllum subsp. serpyllum, T. striatus, and T. vulgaris). Antioxidant effectiveness was assessed using six different assays, in comparison with rosmarinic acid, luteolin, and reference antioxidants. All tested Thymus extracts possessed DPPH (IC50 = 3-6 MUg/mL) and nitric oxide (IC50 = 70-177 MUg/mL) free radical scavenging activities, strong reducing properties (IC50 = 11 15 MUg/mL), ferrous ion chelating activity (IC50 = 126-389 MUg/mL), ability to inhibit lipid peroxidation (IC50 = 34-80 MUg/mL), and high total antioxidant capacities (238-294 mg AAE/g). AChE inhibitory activity was examined using Ellman's colorimetric method and all tested extracts showed anti-AChE activity in a dose dependent manner. The values of 10-28%, 23-39%, and 64-86% were obtained for tested concentrations of 0.25, 0.5, and 1 mg/mL, respectively. Additionally, the contents of total hydroxycinnamic derivatives, flavonoids, and tannins in dried plant samples were determined spectrophotometrically. Our results highlighted Thymus species as a rich source of natural antioxidants and AChE inhibitors that could be useful in preventing and treating Alzheimer's disease and other neurodegenerative disorders. PMID- 26351514 TI - Effect of Ethanol/Water Solvents on Phenolic Profiles and Antioxidant Properties of Beijing Propolis Extracts. AB - Propolis is a natural substance known to be beneficial for human health and used as a folk medicine in many parts of the world. In this study, phenolic profiles and antioxidant properties of Beijing propolis extracted by different ethanol/water solvents were analyzed. Our results reveal that phenolic compounds and antioxidant properties of propolis extracts were significantly dependent on the concentration of ethanol/water solvents. Totally, 29 phenolic compounds were identified: 12 phenolic acids, 13 flavonoids, and 4 phenolic acid esters. In particular, 75 wt.% ethanol/water solvent may be the best for the highest extraction yield and the strongest antioxidant properties. Caffeic acid, benzyl caffeate, phenethyl caffeate, 5-methoxy pinobanksin, pinobanksin, pinocembrin, pinobanksin-3-O-acetate, chrysin, and galangin were the characteristic compounds of Beijing propolis, and these compounds seem to verify that Beijing propolis may be poplar-type propolis. In addition, the presence of high level of pinobanksin-3 O-acetate in Chinese propolis may be a novel finding, representing one-third of all phenolics. PMID- 26351515 TI - Effect and Potential Mechanism of Electroacupuncture Add-On Treatment in Patients with Parkinson's Disease. AB - Objectives. To explore effectiveness and mechanisms of electroacupuncture (EA) add-on treatment in Parkinson's disease (PD) patients. Methods. Fifty PD patients were randomly assigned to drug plus EA (D + EA) group and drug alone (D) group. Subjects in D + EA group received stimulation in points of bilateral fengfu, fengchi, hegu, and central dazhui. Participants were evaluated by scales for motor and nonmotor symptoms. Levels of neuroinflammatory factors and neurotransmitters in serum were detected. Results. EA add-on treatment remarkably reduced scores of Unified Parkinson's Disease Rating Scale (UPDRS) III and its subitems of tremor, rigidity, and bradykinesia and conspicuously decreased UPDRS III scores in patients with bradykinesia-rigidity and mixed types and mild severity. Depression and sleep disturbances were eased, which were reflected by decreased scores of Hamilton Depression Rating Scale, Pittsburgh Sleep Quality Index, and elevated noradrenaline level. Effects of EA add-on treatment on motor symptoms and sleep disturbances were superior to drug alone treatment, markedly improving life quality of PD patients. EA add-on treatment decreased nitric oxide level in serum. Conclusions. EA add-on treatment is effective on most motor symptoms and some nonmotor symptoms and is particularly efficacious in PD patients at early stage. Antineuroinflammation may be a mechanism of EA add-on treatment. PMID- 26351516 TI - Antiatherogenic and Cardioprotective Effects of Black Chokeberry (Aronia melanocarpa) Juice in Aging Rats. AB - Age-related diseases are a social problem of global significance and their prevention by natural products is a research area of particular interest. The present study is an approach to counteract the risk factors for atherosclerosis arising in the aging process by supplementation of chokeberry juice. It employed a model of healthy adult rats monitored for a number of somatometric, serum lipidogram, and histopathological parameters, related to risk factors and their response to supplementation with antioxidant-rich chokeberry juice. The results were used to calculate different atherogenic and cardioprotective indices, and all results were compared to those of young healthy rats. Chokeberry juice proved an extremely rich source of polyphenols resulting in very high antioxidant activity. Treatment with Aronia juice significantly lowered the proatherogenic low-density lipoprotein fraction of the animals studied and led to a 16.5% decrease in their total cholesterol. Atherogenic indices in Aronia-supplemented animals clearly showed lower atherogenic risk and cardioprotective indices indicated protection of the cardiovascular system. Besides that, chokeberry juice retarded the age-related changes in the aortic wall and can be recommended as a prophylactic tool for healthy aging. PMID- 26351517 TI - Effects of Whole-Body Vibration Therapy in Patients with Fibromyalgia: A Systematic Literature Review. AB - Objective. To review the literature on the effects of whole-body vibration therapy in patients with fibromyalgia. Design. Systematic literature review. Patients. Patients with fibromyalgia. Methods. An electronic search of the literature in four medical databases was performed to identify studies on whole body vibration therapy that were published up to the 15th of January 2015. Results. Eight articles satisfied the inclusion and exclusion criteria and were analysed. According to the Dutch CBO guidelines, all selected trials had a B level of evidence. The main outcomes that were measured were balance, fatigue, disability index, health-related quality of life, and pain. Whole-body vibration appeared to improve the outcomes, especially balance and disability index. Conclusion. Whole-body vibration could be an adequate treatment for fibromyalgia as a main therapy or added to a physical exercise programme as it could improve balance, disability index, health-related quality of life, fatigue, and pain. However, this conclusion must be treated with caution because the paucity of trials and the marked differences between existing trials in terms of protocol, intervention, and measurement tools hampered the comparison of the trials. PMID- 26351518 TI - Antinociceptive and Anti-Inflammatory Effects of Total Alkaloid Extract from Fumaria capreolata. AB - Fumaria capreolata is used in traditional medicine in North Africa for its gastrointestinal and anti-inflammatory activities. The present study investigates the effects of total alkaloids extracted from the aerial parts of Fumaria capreolata (AFC) on LPS-induced production of proinflammatory mediators (IL-6, IL 1beta, iNOS, TNF-alpha, COX-2, and MIP-2) in RAW264.7 cells. AFC significantly reduced the inflammatory response inhibiting the production of nitric oxide (NO) and IL-6 in a dose-dependent manner, without affecting the viability of cells, and downregulated mRNA expression of proinflammatory key players: IL-6, IL-1beta, iNOS, TNF-alpha, and COX-2. AFC antinociceptive and anti-inflammatory properties were also evaluated on the acetic acid- and formalin-induced pain models in mice. AFC oral administration significantly inhibited acetic acid-induced writhes and reduced formalin-induced paw licking time. Therefore, AFC may be a potential candidate for the treatment of inflammatory diseases, such as colitis and arthritis. PMID- 26351519 TI - Corrigendum to "Optimization and Corroboration of the Regulatory Pathway of p42.3 Protein in the Pathogenesis of Gastric Carcinoma". PMID- 26351520 TI - Affinity-seq detects genome-wide PRDM9 binding sites and reveals the impact of prior chromatin modifications on mammalian recombination hotspot usage. AB - BACKGROUND: Genetic recombination plays an important role in evolution, facilitating the creation of new, favorable combinations of alleles and the removal of deleterious mutations by unlinking them from surrounding sequences. In most mammals, the placement of genetic crossovers is determined by the binding of PRDM9, a highly polymorphic protein with a long zinc finger array, to its cognate binding sites. It is one of over 800 genes encoding proteins with zinc finger domains in the human genome. RESULTS: We report a novel technique, Affinity-seq, that for the first time identifies both the genome-wide binding sites of DNA binding proteins and quantitates their relative affinities. We have applied this in vitro technique to PRDM9, the zinc-finger protein that activates genetic recombination, obtaining new information on the regulation of hotspots, whose locations and activities determine the recombination landscape. We identified 31,770 binding sites in the mouse genome for the PRDM9(Dom2) variant. Comparing these results with hotspot usage in vivo, we find that less than half of potential PRDM9 binding sites are utilized in vivo. We show that hotspot usage is increased in actively transcribed genes and decreased in genomic regions containing H3K9me2/3 histone marks or bound to the nuclear lamina. CONCLUSIONS: These results show that a major factor determining whether a binding site will become an active hotspot and what its activity will be are constraints imposed by prior chromatin modifications on the ability of PRDM9 to bind to DNA in vivo. These constraints lead to the presence of long genomic regions depleted of recombination. PMID- 26351521 TI - Assessing cardiometabolic risk in middle-aged adults using body mass index and waist-height ratio: are two indices better than one? A cross-sectional study. AB - BACKGROUND: A novel obesity classification method has been proposed using body mass index (BMI) and waist-height ratio (WHtR) together. However, the utility of this approach is unclear. In this study we compare the metabolic profiles in subjects defined as overweight or obese by both measures. We examine a range of metabolic syndrome features, pro-inflammatory cytokines, acute-phase response proteins, coagulation factors and white blood cell counts to determine whether a combination of both indices more accurately identifies individuals at increased obesity-related cardiometabolic risk. METHODS: This was a cross-sectional study involving a random sample of 1856 men and women aged 46-73 years. Metabolic and anthropometric profiles were assessed. Linear and logistic regression analyses were used to compare lipid, lipoprotein, blood pressure, glycaemic and inflammatory biomarker levels between BMI and WHtR tertiles. Multinomial logistic regression was performed to determine cardiometabolic risk feature associations with BMI and WHtR groupings. Receiver operating characteristic curve analysis was used to evaluate index discriminatory ability. RESULTS: The combination of BMI and WHtR tertiles identified consistent metabolic variable differences relative to those characterised on the basis of one index. Similarly, odds ratios of having cardiometabolic risk features were noticeably increased in subjects classified as overweight or obese by both measures when compared to study participants categorised by either BMI or WHtR separately. Significant discriminatory improvement was observed for detecting individual cardiometabolic risk features and adverse biomarker levels. In a fully adjusted model, only individuals within the highest tertile for both indices displayed a significant and positive association with pre-diabetes, OR: 3.4 (95 % CI: 1.9, 6.0), P < 0.001. CONCLUSIONS: These data provide evidence that the use of BMI and WHtR together may improve body fat classification. Risk stratification using a composite index may provide a more accurate method for identifying high and low risk subjects. PMID- 26351522 TI - Constant dedication, passion and devotion for the patients with neurological affections. PMID- 26351523 TI - Medical nutrition therapy in non-alcoholic fatty liver disease--a review of literature. AB - BACKGROUND AND AIM: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease worldwide, with a prevalence of 20%-40% in Western populations. The purpose of this article is to review data related to lifestyle changes in patients with NAFLD. METHOD: We searched a public domain database (PubMed) with the following categories: disease (NAFLD, fatty liver, and non alcoholic steatohepatitis [NASH]) and intervention (lifestyle intervention, diet, nutrition) with each possible combination through 25 September 2014, for relevant articles. Review of articles was restricted to those published in English. We selected the studies involving adult patients only. CONCLUSION: There is no consensus as to what diet or lifestyle approach is the best for NAFLD patients. However, patients with NAFLD may benefit from a moderate- to low-carbohydrate (40%-45% of total calories) diet, coupled with increased dietary MUFA and n-3 PUFAs, reduced SFAs. More CRT are needed to clarify the specific effects of different diets and dietary components on the health of NAFLD patients. ABBREVIATIONS: NAFL = Non-alcoholic fatty liver, NAFLD = non-alcoholic fatty liver disease, NASH = non-alcoholic steatohepatitis, HCC = hepatocarcinoma, BEE = basal energy expenditure, CRT = A small clinical randomized trial showed that short-term carbohydrate restriction is more efficacious in reducing intrahepatic triglyceride, IHT = intrahepatic triglyceride, VLCD = Very low calorie diets, AST = aspartate aminotransferases, SFAs = saturated fatty acids. PMID- 26351524 TI - Total pelvic exenteration for pelvic recurrence after advanced epithelial ovarian cancer--A case report and literature review. AB - Ovarian cancer is an aggressive disease, which, although associated with a high rate of recurrence, seems to benefit most from iterative cytoreduction. Although the main patterns of its spreading are represented by peritoneal, lymphatic or hematogenous route, local recurrences might also be seen. Whenever pelvic recurrence develops, complete resections based on the ultraradical principles applied in resections for pelvic recurrences originating from cervical cancer, are useful. We present the case of a 56-year-old patient who was diagnosed with a pelvic recurrence invading both the urinary bladder and the anterior rectal wall two years and a half after a surgery for stage IIIC ovarian cancer. PMID- 26351525 TI - Brain-heart axis--Review Article. AB - There has been a large confirmation over the last decades that stroke may produce cardiac changes (echocardiographic, electrocardiographic, enzymatic). In ischemic stroke, systolic dysfunction is associated with a high risk of mortality during hospitalization. A recent study demonstrated that cardiac diastolic dysfunction could also accompany acute stroke besides the systolic dysfunction already pointed out by previous studies, being a predictive marker of acute cerebrovascular events. Increased sympathetic activity is contributory, inducing a reversible cardiac myocyte damage and cardiac enzyme surges. Some of the most frequent electrocardiographic abnormalities in stroke are ST segment abnormalities and various tachyarrhythmias (especially atrial fibrillation) and bradyarrhythmias. One can infer the importance of careful and continuous electrocardiographic monitoring of the stroke patient in order to identify these quite frequent electrocardiographic alterations, as it is well known that death due to cardiac arrhythmias is common among acute stroke patients. In order to increase the diagnostic yield, a high level of NTproBNP (N-terminal of the prohormone brain natriuretic peptide) may be used as a discriminant for the patients with a higher probability of cardiac arrhythmias and mortality at presentation, during hospitalization and on the long term. In such patients, cardiac monitoring techniques are more likely to reveal abnormalities. A high BNP level may have potentially important management implications as it may signal a worse prognosis and may prompt the undertaking of certain therapeutic measures. This review summarizes the possible pathological mechanisms of heart-brain connections and their clinical and therapeutical implications. ABBREVIATIONS: AF = atrial fibrillation, ECG = electrocardiography, HRV = heart rate variability, cTn = cardiac troponin, SAH = subarachnoid hemorrhage, CK-MB = creatine kinase MB, BNP = brain natriuretic peptide, NT-proBNP = N-terminal of the prohormone brain natriuretic peptide, ANP = atrial natriuretic peptide, mRS = modified Rankin Scale, NIHSS = the National Institutes of Health Stroke Scale. PMID- 26351526 TI - Actual data on epidemiological evolution and prevention endeavours regarding traumatic brain injury. AB - BACKGROUND: Knowledge of the epidemiology of traumatic brain injury (TBI) is required both to prevent this disorder and to develop effective care and rehabilitation approaches for patients. OBJECTIVE: The aim of this article is to find solutions to decrease the incidence of TBI and offer recommendations for their prevention. MATERIAL AND METHODS: We analyzed epidemiological studies on TBI by performing a systematic review of literature, using information reported by different centers, collecting data on demographics, showing characteristics of TBI including incidence, identification of risk groups on differences in age, gender, geographical variation, severity and mortality. RESULTS: Studies suggest that the incidence of TBI is between 18 and 250 per 100,000 persons per year. Men and people living in social and economical deprived areas, usually young adults and the elderly are high-risk groups for TBI. DISCUSSION: Prevention remains the "key point" in medicine and especially for TBI, saving the patient from unnecessary often-harsh sufferance. CONCLUSIONS: Most public epidemiological data showed that TBI is a major cause of mortality and disability. The effort to understand TBI and the available strategies to treat this lesion, in order to improve clinical outcomes after TBI, may be based on an increase in research on the epidemiology of TBI. A coordinated strategy to evaluate this public health problem in Romania would first of all rely on a related advanced monitoring system, to provide precise information about the epidemiology, clinical and paraclinical data, but concerning the social and economic connected consequences, too. ABBREVIATIONS: CNS = central nervous system, ED = emergency department, EU = European Union, FTE = Full Time Employees, GCS = Glasgow Coma Scale, TBI = traumatic brain injury, US = United States, WHO = World Health Organization. PMID- 26351527 TI - Current diagnosis and treatment of chronic subdural haematomas. AB - A developed society is usually also characterized by an elderly population, which has a continuous percentage growth. This population frequently presents a cumulus of medical pathologies. With the development of the medication and surgical treatment of different affections, the life span has increased and the pathology of an old patient has diversified as far as the cumulus of various pathological diseases in the same person is concerned. Chronic subdural pathologies represent an affection frequently met in neurosurgery practice. Any neurosurgeon, neurologist and not only, has to be aware of the possibility of the existence of a chronic subdural haematoma, especially when the patient is old and is subjected to an anticoagulant or antiaggregant treatment, these 2 causes being by far the etiological factors most frequently met in chronic subdural haematomas. With an adequate diagnosis and treatment, usually surgical, the prognosis is favorable. Although the surgical treatment presents a categorical indication in most of the cases, the fact that there are many surgical techniques, a great relapse rate, as well as the numerous studies, which try to highlight the efficiency of a technique as compared to another, demonstrate that the treatment of these haematomas is far from reaching a consensus among the neurosurgeons. The latest conservatory treatment directions are still being studied and need many years to be confirmed. ABBREVIATIONS: CT = computerized tomography, MRI = magnetic resonance imaging. PMID- 26351528 TI - Quantification of liver fibrosis in chronic hepatitis B virus infection. AB - Chronic hepatitis B virus infection (HBV) is considered a global public issue with more than 78.000 people per year dying of its evolution. With liver transplantation as the only viable therapeutic option but only in end-stage disease, hepatitis B progression may generally be influenced by various factors. Assessing fibrosis stage plays an important part in future decisions on the patients' wealth with available antiviral agents capable of preventing fibrosis passing to an end-stage liver disease. Several methods have been taken into consideration as an alternative for HBV quantification status, such as imaging techniques and serum based biomarkers. Magnetic resonance imaging, ultrasound, and elastography are considered non-invasive imaging techniques frequently used to quantify disease progression as well as patients future prognostic. Consequently, both direct and indirect biomarkers have been studied for differentiating between fibrosis stages. This paper reviews the current standings in HBV non-invasive liver fibrosis quantification, presenting the prognostic factors and available assessment procedures that might eventually replace liver biopsy. PMID- 26351529 TI - Features of Polycystic Ovary Syndrome in adolescence. AB - RATIONALE: To elucidate the prepubertal risk factors associated with the development of Polycystic Ovary Syndrome (PCOS) and determine the special clinical manifestations of the syndrome in this transitional time of a woman's life. OBJECTIVE: To propose therapeutic targets and regimens, not only to prevent the long-term complications of the syndrome, but also to improve the self-esteem of a young girl who matures into womanhood. METHODS AND RESULTS: A systematic review of literature was performed through electronic database searches (Pubmed, Medline and Embase). Studies published in English-language, peer-reviewed journals from 1996 to 2013 were included. The selected studies focused on the risk factors, the unique features and treatment options of the PCOS in puberty. The pathogenesis of the PCOS was hypothesized to be based on interactions between genetic and certain environmental factors. The diagnosis was usually difficult in young girls. The syndrome was related to a greater risk of future infertility, type II diabetes mellitus, the metabolic syndrome and cardiovascular disease. Early treatment was crucial to prevent the long-term complications of the syndrome, especially infertility and cardiovascular disease. DISCUSSION: The recognition of the early signs of PCOS during or even before adolescence is of great importance. It is essential to establish the correct diagnosis for PCOS and rule out other causes of androgen excess in young women with hyperandrogenism. The type of treatment applied should be considered on an individual basis. ABBREVIATIONS: PCOS = Polycystic Ovary Syndrome. PMID- 26351530 TI - Preliminary results of using ALAnerv(r) in subacute motor incomplete paraplegics. AB - RATIONALE: To assess whether using ALAnerv(r) contributes to improvements of outcomes obtained in post SCI patients. OBJECTIVE: A prospective controlled clinical survey also to evaluate the safety and efficacy of ALAnerv(r) (2cps/ day for 28 days) in motor incomplete (AIS/ Frankel C) paraplegic subacute patients. METHODS AND RESULTS: 59 patients divided in study (treated with ALAnerv(r)) and control, groups. This survey's follow-up duration was of 28 days. Most of the studied patients were mid-aged (mean 43.75 years old) and respectively, men (64,29% in the study group; 58,06% in controls). We used descriptive statistics (functions: minimum, maximum, mean, median, standard deviation) and for related comparisons, parametric (Student t) and non-parametric (Mann-Whitney, Fisher's exact, chi-square) tests. The primary end-point: AIS motor values' evolution (P= 0.015 - Mann-Whitney), showed that patients treated with ALAnerv(r) - vs. controls - had a statistically significant better increase of such scores at discharge. Paraclinical parameters, mainly exploring systemic inflammatory status (secondary end-point): ESR dynamics (P=0.13) had no statistical significance; the plasma leucocytes number (P=0.018), the neutrophils' percentage (P=0.001) and fibrinogenemia (P= 0,017) proved in the treated group to have a statistically significant better evolution. We used "Statistical Package for Social Sciences" (SPSS). DISCUSSION: As there is actually no effective curative solution for the devastating pathology following SCI, any medical approach susceptible to bring even limited improvements, such as treatment with ALAnerv(r) seemed to have proven, is worth being surveyed, under strict circumstances of ethics and research methodology. Considering the necessity for more statistical power concerning primary, secondary end-points, and safety issues, as well, continuing this research is needed. ABBREVIATIONS: SCI = spinal cord injury, TSCI = traumatic spinal cord injury, BBB = blood brain barrier, CNS = central nervous system, SC = spinal cord, NSAIDs = non-steroidal anti-inflammatory drugs, SAIDs = steroidal anti-inflammatory drugs, AIS = American Spinal Injury Association Impairment Scale, SPSS = Statistical Package for Social Sciences, BATEH = Bagdasar-Arseni Teaching Emergency Hospital. PMID- 26351531 TI - Project for the National Program of Early Diagnosis of Endometrial Cancer Part I. AB - RATIONALE: Endometrial cancer recorded a peak incidence in ages 60-64 years in Romania, reaching in 2013 the average value of 8.06/ 100,000 women, and 15.97/ 100,000 women within the highest risk age range, having in recent years an increasing trend, being higher in urban than in rural population. Annually, approximately 800 new cases are registered in our country. The estimated lifetime risk of a woman to develop endometrial cancer is of about 1,03%. Based on an abnormal uterine bleeding, 35% of the endometrial cancers are diagnosed in an advanced stage of the disease, with significantly diminished lifetime expectancy. OBJECTIVE: Drafting a national program for the early diagnosis of endometrial cancer. METHODS AND RESULTS: We proposed a standardization of the diagnostic steps and focused on 4 key elements for the early diagnosis of endometrial cancer: investigation of abnormal uterine bleeding occurring in pre/ post menopausal women, investigating features/ anomalies of cervical cytology examination, diagnosis, treatment and proper monitoring of precursor endometrial lesions or cancer associated endometrial lesions and screening high risk populations (Lynch syndrome, Cowden syndrome). DISCUSSION: Improving medical practice based on diagnostic algorithms addresses the four risk groups, by improving information system reporting and record keeping. Improving addressability cases by increasing the health education of the population will increase the rate of diagnosis of endometrial cancer in the early stages of the disease. ABBREVIATIONS: ACOG = American Society of Obstetricians and Gynecologists, ASCCP = American Society for Colposcopy and Cervical Pathology, PATT = Partial Activated Thromboplastin Time, BRCA = Breast Cancer Gene, CT = Computerized Tomography, IFGO = International Federation of Gynecology and Obstetrics, HLG = Hemoleucogram, HNPCC = Hereditary Nonpolyposis Colorectal Cancer (Lynch syndrome), IHC = Immunohistochemistry, BMI = Body Mass Index, INR = International Normalized Ratio, MSI = Microsatellites instability, MSI-H/ MSI-L = high (positive test)/ low (negative test) microsatellites instability, WHO = World Health Organization, PCR = Polymerase chain reaction, MRI = Magnetic Resonance Imaging, SGO = Society of Gynecologic Oncologists, SHG = Sonohysterography, SRU = Society of Radiologists in Ultrasound, TQ = Time Quick, BT = Bleeding Time, TVUS = Transvaginal ultrasound, USPIO = Ultrasmall superparamagnetic iron oxide. PMID- 26351532 TI - Trigger points--ultrasound and thermal findings. AB - RATIONALE: Muscle pain can be elicited by any irritation of the nociceptors in the muscle or central sensitization in the central nervous system. The most frequently described muscle pain syndromes are myofascial pain syndrome and fibromyalgia syndrome. Myofascial pain syndrome has a more localized manifestation, the trigger points. OBJECTIVE: If there is a correlation between the clinical findings, the ultrasound examination and the thermal pattern of trigger points exist. MATERIAL AND METHOD: The presence of trigger points can be identified by using clinical criteria. An ultrasound examination was performed to evaluate the trigger point dimensions. The ultrasound showed an ellipsoidal hypoechogenic area in the muscle. A thermography of the low back region was performed in order to observe the thermal pattern of the area. RESULTS: Trigger points are represented by a higher temperature area surrounded by a cooler area, probably caused by a deficit in the blood flow around those points. DISCUSSION: Infrared thermography could be a great asset for the monitoring of neuromusculoskeletal disorders and their dynamics, as well as an important aid for the initial diagnosis of conditions associated with tissue temperature alterations. PMID- 26351533 TI - Acute anterior uveitis and other extra-articular manifestations of spondyloarthritis. AB - BACKGROUND: Spondyloarthritis (SpA) is associated with an array of peripheral manifestations. Our study aims to evaluate extra-articular manifestations of SpA in a Romanian academic clinical setting and to observe their associations with different disease measures. METHODS: The study was designed to note the extra articular manifestations of SpA patients in a cross-sectional and retrospective manner. Records included demographics, inflammation markers, SpA clinical characteristics, treatment regimes, associated osteoporosis and cardiovascular morbidity. Data were assessed by using appropriate non-parametric tests. RESULTS: A total of 126 SpA patients were included. The most common extra-articular manifestations were skin involvement in the form of psoriasis (34.1%), eye involvement in the form of acute anterior uveitis (8.7%) and dactylitis (7.2%). Compared to patients with no record of uveitis, uveitis-affected cases were more frequently males, more frequently diagnosed with ankylosing spondylitis, but less frequently dyslipidemic and diagnosed with psoriasis. Psoriasis-affected patients were older and had a higher prevalence of peripheral SpA diagnosis, but a lower prevalence of radiographic sacroiliitis. CONCLUSIONS: Acute anterior uveitis in SpA predominantly affects males with AS. This is relevant both to clinical and fundamental science, since its management requires both ophthalmology and rheumatology clinical settings. Psoriasis was associated more frequently with peripheral SpA. ABBREVIATIONS: AHT = arterial hypertension, AS = ankylosing spondylitis, ASAS = Assessment in SpondyloArthritis international Society, aSpA = axial spondyloarthritis, BASFI = Bath Ankylosing Spondylitis Functional Index, BASDAI = Bath Ankylosing Spondylitis Disease Activity Index, CRP = C-reactive protein, ESR = erythrocyte sedimentation rate, DM2 = type 2 diabetes mellitus, HLA = human leukocyte antigen, IBD = inflammatory bowel disease, MRI = magnetic resonance imaging, mSpA = mixed (peripheral and axial) spondyloarthritis, NSAIDs = non-steroidal anti-inflammatory drugs, pSpA = peripheral spondyloarthritis, PsA = psoriatic arthritis, ReA = reactive arthritis, SD = standard deviation, SI = sacroiliitis, SpA = spondyloarthritis, UDSpA = undifferentiated spondyloarthritis. PMID- 26351534 TI - Combination therapy--a way to forestall artemisinin resistance and optimize uncomplicated malaria treatment. AB - Artemisinin resistance represents a global concern, which requires a concerted and coordinated effort at a global level. Lessons learned from the experience of drug combination therapies in HIV, TB, and HCV infections showed that combination therapies reduce the risk of drug resistance development. In order to maximize the effectiveness of artemisinin and its derivates and to protect it from the development of resistance, WHO recommended that they should be combined with other drugs that have different mechanisms of action and longer half-lives. Until the attainment of new pharmaceuticals, artemisinin-based combination therapy (ACT) is the way to forestall artemisinin resistance and optimize uncomplicated malaria treatment. PMID- 26351535 TI - Complications in cochlear implant surgery. AB - For the last 6 years, cochlear implantation has become a standard practice in our department. The number of patients rose from 5 to 21/ year. Using multiple types of cochlear implants and indicating the surgery also to malformed inner ears led to the encounter of some complications. OBJECTIVE: to present the surgical complications from our department. MATERIAL: all the patients admitted and operated in our clinic have been reviewed. RESULTS: 9 complications (8,86%) have occurred: the impossibility of establishing a reliable cochleostomy (due to ossification), air in the cochlea through lack of sealing of the cochleostomy (exteriorization of the electrode array), cochlear implant postoperative migration from its bed, weak hearing discrimination due to "double electrodes" in the scala tympani, gusher. CONCLUSIONS: cochlear implanting needs to respect the technical steps of the surgery and the best technical/ tactical solution has to be found to whatever complications arise in complex or malformed cases! PMID- 26351536 TI - A strategy to identify opportunities for innovation in Romanian healthcare services. AB - In principle, the development of medicine (including the Romanian health system) is primarily dependent on the level of funding and the efficiency with which this funding is used, the structure of the population and socio-economic development of the geographical area concerned, and not least, the attitudes and expectations of patients, which in turn translate into care taking policies system. Unlike the other services, health services are accessed by a large number of people, which results into high health. As an economic principle, the fewer resources are used to achieve the expected results, the more effective the supplier. However, the introduction of new medical technologies, many of them more reliable yet more expensive, required a reassessment of the way resources are used at the suppliers' level to produce the expected results, an evaluation based on cost effectiveness per analysis (or per patient) criteria. Finally, medical services are the tools of the marketing strategy of any medical organizations without which the needs and motivations of the beneficiaries (patients) could not be satisfied. In essence, the entire marketing philosophy is based on the needs and wishes of the people and on concrete solutions to solve them. PMID- 26351537 TI - Genetic factors involves in intracranial aneurysms--actualities. AB - Intracranial aneurysm (IA) is a common vascular disorder, which frequently leads to fatal vascular rupture leading to subarachnoid hemorrhage (SAH). Although various acquired risk factors associated with IAs have been identified, heritable conditions are associated with IAs formation but these syndromes account for less than 1% of all IAs in the population. Cerebral aneurysm disease is related to hemodynamic and genetic factors, associated with structural weakness in the arterial wall, which was acquired by a specific, often unknown, event. Possibly, the trigger moment of aneurysm formation may depend on the dynamic arterial growth, which is closely related to aging/ atherosclerosis. Genetic factors are known to have an important role in IA pathogenesis. Literature data provide complementary evidence that the variants on chromosomes 8q and 9p are associated with IA and that the risk of IA in patients with these variants is greatly increased with cigarette smoking. Intracranial aneurysms are acquired lesions (5 10% of the population). In comparison with sporadic aneurysms, familial aneurysms tend to be larger, more often located in the middle cerebral artery, and more likely to be multiple. ABBREVIATIONS: DNA = deoxyribonucleic acid, FIA = familial Intracranial Aneurysm, GWAS = genome-wide association studies, IL-6 = interleukin 6, ISUIA = International Study of Unruptured Intracranial Aneurysms, IA = Intracranial aneurysm, mRNA = Messager ribonucleic acid, SNPs = single-nucleotide polymorphisms, SMCs = smooth muscle cells, sIAs = sporadic IAs, SAH = subarachnoid hemorrhage, TNF-alpha = tumor necrosis factor-alpha, COL4A1 = type IV collagen alpha-1. PMID- 26351538 TI - The laparoscopic management of simple hepatic cysts. AB - The hepatic polycystic disease represents a hereditary condition with a reduced prevalence in the general population, sometimes associated with polycystic kidney disease. We present a retrospective observational study applied to 49 patients. The study aimed to observe the laparoscopic surgery of simple hepatic cysts. Laparoscopic approach is a simple and successful surgery management of these types of cysts. PMID- 26351539 TI - Thermal patterns in zoster. AB - RATIONALE: Varicella zoster virus is a neurotropic virus that causes an infectious disease characterized by skin changes and neuropathic pain. After the resolution of the first infection, the virus lies dormant within the sensory ganglia. The reactivation of the virus causes zoster. An alteration in skin infrared emission might be expected in the areas of the skin affected by inflammatory changes and demyelination of the affected peripheral nerve. OBJECTIVE: To establish the importance of thermal imaging in the follow up of Zoster Zone with different localization. An infrared thermal camera was used in order to assess if the evolution of the disease determines a thermal pattern. METHODS AND RESULTS: Infrared thermography can be used for the assessment of the affected area also by using a thermography camera that is sensitive to the infrared spectrum. An intense and diffuse infrared emission is highly suggestive for the inflammation and implies that a more aggressive treatment should be initiated. After the clinical resolution of the affected area, the symmetry of the thermal pattern should be restored. If the asymmetry persists, a neuropathic complication of the virus reactivation could be involved. DISCUSSIONS: The integration of infrared thermography with the clinical findings is very useful in order to create a complete picture of the zoster lesions and this method could determine the beginning of a correct treatment and, by doing so, minimizing the risk of complications. PMID- 26351540 TI - Predictors for length of hospital stay after inguinal hernia surgery. AB - AIM: identifying the variables that can help in quantifying/ predicting duration of hospital stay after inguinal hernia surgery. METHOD: 257 patients who were diagnosed with inguinal hernia underwent surgery between January 2013 and October 2014 and were prospectively registered and statistically analyzed by using linear regression with the aim of emphasizing, calculating and validating the predictors for duration of hospital stay. RESULTS: out of 257 patients, 50,7% underwent laparoscopic surgery (TAPP and TEP) and 49,7% had an anterior approach by using the technique described by Lichtenstein in most of the cases. From the variables registered in the study (age, recurrence, emergency surgery, ASA [American Society of Anesthesiologists] risk classification, surgery duration, local and general complications) only the age and presence/absence of complications were statistically associated with the modification of the duration of hospital stay in this pathology. CONCLUSIONS: the duration of hospital stay can be evaluated preoperatory by using a mathematical model, which takes into consideration factors that depend on the patient or the procedure, with results that can have a significant impact on planning the local resources. PMID- 26351541 TI - Bleeding gastric cancer in young and elderly patients. AB - PURPOSE: This study tried to find the differences between gastric cancer in young and elderly, in addition through the importance of the presence of the upper gastrointestinal bleeding, with two examples of clinical cases. METHODS: Two groups of patients divided by age were compared. The first group consisted of 13 cases of patients aged between 32 and 41, and the second consisted of 15 cases, aged 80 to 87 years. The variables considered were: sex, personal history and family history, onset-admission interval, number of days of hospitalization after surgery, the number of days until discharge, personal history/ family history, tumor location, admission diagnosis, intervention type, value hemoglobin on admission, the way externalizing hemorrhage appeared, stage, tumor type/ degree of differentiation of its kind lymph dissection, postoperative complications and deaths. RESULTS: The interval from symptom onset to hospital admission was higher in young people with a greater weight loss and malignant ulcer history or upload family were smokers, but apparently with a lower complication rate. In the elderly, the anemic syndrome was the main event and the complications were more related to comorbidities. CONCLUSIONS: Prolonged gastric distress in young patients, associated with smoking, personal history of ulcer and family history of neoplasia should guide the diagnosis to gastric cancer. Anemic syndrome in the elderly may be due to the gastric cancer, and complications are due to comorbidities. PMID- 26351542 TI - Subcutaneous metastasis--the first sign of hepatocellular carcinoma in chronic virus C hepatitis patient--Case report. AB - Hepatocellular carcinomas make up 90% of primary liver cancers. The association between the hepatic carcinoma and virus B and C infection has been already proven. Hepatocellular carcinoma develops, in most cases, on a background of cirrhosis and rarely in hepatitis. The case we have chosen to report distinguishes itself due to the unusual extra-hepatic metastatic location of a hepatocellular carcinoma in a patient with Chronic HCV hepatitis. PMID- 26351543 TI - Mucormycosis during Imatinib treatment: case report. AB - Philadelphia chromosome positive acute lymphoblastic leukemia is classified as a very high-risk group and it requires an intensive chemotherapy regimen associated with tyrosine-kinase inhibitors and allogeneic hematopoietic stem cell transplant from related or unrelated HLA matched donor. Most times, intensive chemotherapy regimens are associated with prolonged and profound pancytopenia when the risk of invasive fungal infection increases. After Candida and Aspergillus species, Mucormycosis is the third frequent fungal infection in hematology patients and it is associated with a reduced overall survival. When suspected, immediate treatment is needed. We present the case of 24-year-old patient diagnosed with Philadelphia chromosome positive acute lymphoblastic leukemia who developed right rhino-sino-orbital fungal infection with a favorable response to systemic antifungal treatment and noninvasive surgery. Later, patient refused consolidation and allogeneic hematopoietic stem cell transplant from an unrelated HLA matched donor but accepted the first generation tyrosine kinase inhibitor (Imatinib) and maintained a complete hematological and molecular response. ABBREVIATIONS: ENT = ear nose throat; BMB = bone marrow biopsy; ALL = acute lymphoblastic leukemia; TKI = tyrosine kinase inhibitor; IFI = invasive fungal infection; BMB = bone marrow biopsy; HE = hematoxylin and eosin; IHC = immunohistochemistry; CD = cluster of differentiation; ob = objective; Tdt = terminal deoxynucleotidyl transferase. PMID- 26351544 TI - Determining factors of diuresis in chronic kidney disease patients initiating hemodialysis. AB - BACKGROUND: Patients with stage 5 chronic kidney disease (CKD) begin chronic hemodialysis with variable diuresis levels correlated to a comparable low glomerular filtration rate. Residual diuresis influences long-term evolution of the hemodialyzed patient, modifying the prognosis even if optimal Kt/ V is achieved. AIM OF THE STUDY: The present study emphasizes the main determining factors of diuresis in a cohort of stage 5 CKD subjects at the beginning of hemodialysis. MATERIAL AND METHODS: 216 patients with stage 5 CKD starting chronic hemodialysis were included in the study, and were grouped according to their residual diuresis: group A (urine output <= 500 mL/ day); group B (urine output between 500-1200 mL/ day); group C (urine output >= 1200 mL/ day). RESULTS: Glomerular etiology, cardiac systolic dysfunction, severe malnutrition, emergency dialysis initiation and lack of permanent vascular access were proved to be associated with significant low diuresis. Age, gender, estimated glomerular filtration rate (GFR) and the presence of systemic hypertension did not influence the amount of daily diuresis. CONCLUSIONS: In CKD stage 5 patients, residual diuresis presents large variations in conditions of comparable low GFR. Factors influencing residual diuresis may be distinct from those that influence residual GFR. PMID- 26351545 TI - Low-frequency rTMS in patients with subacute ischemic stroke: clinical evaluation of short and long-term outcomes and neurophysiological assessment of cortical excitability. AB - RATIONALE: Repetitive transcranial magnetic stimulation (rTMS) is used alone or in combination with physiotherapy for rehabilitation of stroke patients. TMS mapping can also quantify the excitability of the motor area in both the ipsilesional (IL) and contralateral (CL) hemisphere. OBJECTIVE: This study is the first to measure the dynamics of cortical excitability by TMS mapping before and after treatment with low-frequency (LF) rTMS in the contralesional hemisphere at three different timepoints. Furthermore, the patients were clinically evaluated during the same visit as the mapping to establish both short and long-term outcomes after rTMS treatment. METHODS AND RESULTS: A total of 16 participants with acute ischemic stroke were assessed 10 days post-stroke by TMS mapping. The patients were randomized into two equal groups: a real rTMS group and a sham group. The rTMS group received LF-rTMS to the contralesional hemisphere for 10 days, starting on the first day after the first mapping. Each subject was also evaluated by mapping on days 45 and 90 after stroke onset. The primary clinical outcome measured was the Fugl-Meyer Assessment for Upper Extremity (FMA-UE) on days 10, 45 and 90 post-stroke. At 10 days after stroke onset, both groups presented low excitability in the lesion side and high excitability in the non affected side. In the real rTMS group, at 45 days after stroke, a downward trend in the excitability of the contralesional hemisphere and an upward trend in the excitability of the lesioned side were observed. At 90 days after stroke, a tendency toward balanced excitability between both hemispheres was observed. In the sham group, at both 45 and 90 days, we observed increased excitability in the non-affected side compared to the side with the lesioned motor area. At 45 days, the real rTMS group demonstrated a better recovery of the upper limb motor function than the sham group, but at 90 days, there was no significant difference between the two groups. DISCUSSION: These results demonstrated that LF-rTMS treatment enhances rebalance of the excitability patterns in both hemispheres and led us to question the "one size fits all" approach widely used in rTMS interventions. ABBREVIATIONS: Amax = maximum amplitude, Amean = AM = averaged amplitude, APB = abductor pollicis brevis, CL = contralesional, DTI = diffusion tensor imaging, EEG = electroencephalography, EMG = electromyography, FMA-UE = Fugl-Meyer Assessment for Upper Extremity, HS = hot spot, IHC = interhemispheric functional connectivity, IL = ipsilesional, LF-rTMS = low-frequency repetitive transcranial magnetic stimulation, MCA = middle cerebral artery, MEP(s) = motor evoked potential(s), NIBS = non-invasive brain stimulation, rMT = resting motor threshold, RP = responsive points, rTMS = repetitive transcranial magnetic stimulation, TMS = transcranial magnetic stimulation. PMID- 26351546 TI - Congenital scoliosis: an up-to-date. AB - Congenital scoliosis represents a spinal malformation due to defects of formation, segmentation or mixed ones. It is characterized by a longitudinal and rotational imbalance. 54 patients were analyzed and 39 out of them were operated by various approaches with anterior and posterior instrumentations during 2000 and 2012. The impossibility to appoint some patients encountered in the daily practice into the known classifications, allowed us to purpose two categories of congenital scoliosis related to the predominance of spinal deviances in the coronal and transversal views. No certain etiology of congenital scoliosis has been identified until today. The susceptibility of some polygenic defects is obvious due to the presence of a sum of defects associated to most of the congenital scoliosis cases and the rarity of the presence of a unique defect. The diagnosis requires a thorough clinical and imaging examination in order to establish an individualized therapeutic strategy. The treatment of congenital scoliosis is different from the adolescent idiopathic one. Therapeutic criteria are significantly different. It is essential to assess the difference in growth of the concavity related to the convexity when choosing a particular procedure. The magnitude of the curve and the progressive rate are fundamental issues to the surgeon. PMID- 26351547 TI - Predictive cytogenetic biomarkers for colorectal neoplasia in medium risk patients. AB - RATIONALE: DNA damage and chromosomal alterations in peripheral lymphocytes parallels DNA mutations in tumor tissues. OBJECTIVE: The aim of our study was to predict the presence of neoplastic colorectal lesions by specific biomarkers in "medium risk" individuals (age 50 to 75, with no personal or family of any colorectal neoplasia). METHODS AND RESULTS: We designed a prospective cohort observational study including patients undergoing diagnostic or opportunistic screening colonoscopy. Specific biomarkers were analyzed for each patient in peripheral lymphocytes - presence of micronuclei (MN), nucleoplasmic bridges (NPB) and the Nuclear Division Index (NDI) by the cytokinesis-blocked micronucleus assay (CBMN). Of 98 patients included, 57 were "medium risk" individuals. MN frequency and NPB presence were not significantly different in patients with neoplastic lesions compared to controls. In "medium risk" individuals, mean NDI was significantly lower for patients with any neoplastic lesions (adenomas and adenocarcinomas, AUROC 0.668, p 00.5), for patients with advanced neoplasia (advanced adenoma and adenocarcinoma, AUROC 0.636 p 0.029) as well as for patients with adenocarcinoma (AUROC 0.650, p 0.048), for each comparison with the rest of the population. For a cut-off of 1.8, in "medium risk" individuals, an NDI inferior to that value may predict any neoplastic lesion with a sensitivity of 97.7%, an advanced neoplastic lesion with a sensitivity of 97% and adenocarcinoma with a sensitivity of 94.4%. DISCUSSION: NDI score may have a role as a colorectal cancer-screening test in "medium risk" individuals. ABBREVIATIONS: DNA = deoxyribonucleic acid; CRC = colorectal cancer; EU = European Union; WHO = World Health Organization; FOBT = fecal occult blood test; CBMN = cytokinesis-blocked micronucleus assay; MN = micronuclei; NPB = nucleoplasmic bridges; NDI = Nuclear Division Index; FAP = familial adenomatous polyposis; HNPCC = hereditary non-polypoid colorectal cancer; IBD = inflammatory bowel diseases; ROC = receiver operating characteristics; AUROC = area under the receiver operating characteristics curve. PMID- 26351548 TI - The epigenetic signature of subcutaneous fat cells is linked to altered expression of genes implicated in lipid metabolism in obese women. AB - BACKGROUND: Obesity is associated with changes in fat cell gene expression and metabolism. What drives these changes is not well understood. We aimed to explore fat cell epigenetics, i.e., DNA methylation, as one mediator of gene regulation, in obese women. The global DNA methylome for abdominal subcutaneous fat cells was compared between 15 obese case (BMI 41.4 +/- 4.4 kg/m(2), mean +/- SD) and 14 never-obese control women (BMI 25.2 +/- 2.5 kg/m(2)). Global array-based transcriptome analysis was analyzed for subcutaneous white adipose tissue (WAT) from 11 obese and 9 never-obese women. Limma was used for statistical analysis. RESULTS: We identified 5529 differentially methylated DNA sites (DMS) for 2223 differentially expressed genes between obese cases and never-obese controls (false discovery rate <5 %). The 5529 DMS displayed a median difference in beta value of 0.09 (range 0.01 to 0.40) between groups. DMS were under-represented in CpG islands and in promoter regions, and over-represented in open sea-regions and gene bodies. The 2223 differentially expressed genes with DMS were over represented in key fat cell pathways: 31 of 130 (25 %) genes linked to "adipogenesis" (adjusted P = 1.66 * 10(-11)), 31 of 163 (19 %) genes linked to "insulin signaling" (adjusted P = 1.91 * 10(-9)), and 18 of 67 (27 %) of genes linked to "lipolysis" (P = 6.1 * 10(-5)). In most cases, gene expression and DMS displayed reciprocal changes in obese women. Furthermore, among 99 candidate genes in genetic loci associated with body fat distribution in genome-wide association studies (GWAS); 22 genes displayed differential expression accompanied by DMS in obese versus never-obese women (P = 0.0002), supporting the notion that a significant proportion of gene loci linked to fat distribution are epigenetically regulated. CONCLUSIONS: Subcutaneous WAT from obese women is characterized by congruent changes in DNA methylation and expression of genes linked to generation, distribution, and metabolic function of fat cells. These alterations may contribute to obesity-associated metabolic disturbances such as insulin resistance in women. PMID- 26351549 TI - Health Care for People Approaching the End of Life: An Evidentiary Framework. PMID- 26351550 TI - The Determinants of Place of Death: An Evidence-Based Analysis. AB - BACKGROUND: According to a conceptual model described in this analysis, place of death is determined by an interplay of factors associated with the illness, the individual, and the environment. OBJECTIVES: Our objective was to evaluate the determinants of place of death for adult patients who have been diagnosed with an advanced, life-limiting condition and are not expected to stabilize or improve. DATA SOURCES: A literature search was performed using Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid Embase, EBSCO Cumulative Index to Nursing & Allied Health Literature (CINAHL), and EBM Reviews, for studies published from January 1, 2004, to September 24, 2013. REVIEW METHODS: Different places of death are considered in this analysis-home, nursing home, inpatient hospice, and inpatient palliative care unit, compared with hospital. We selected factors to evaluate from a list of possible predictors-i.e., determinants-of death. We extracted the adjusted odds ratios and 95% confidence intervals of each determinant, performed a meta-analysis if appropriate, and conducted a stratified analysis if substantial heterogeneity was observed. RESULTS: From a literature search yielding 5,899 citations, we included 2 systematic reviews and 29 observational studies. Factors that increased the likelihood of home death included multidisciplinary home palliative care, patient preference, having an informal caregiver, and the caregiver's ability to cope. Factors increasing the likelihood of a nursing home death included the availability of palliative care in the nursing home and the existence of advance directives. A cancer diagnosis and the involvement of home care services increased the likelihood of dying in an inpatient palliative care unit. A cancer diagnosis and a longer time between referral to palliative care and death increased the likelihood of inpatient hospice death. The quality of the evidence was considered low. LIMITATIONS: Our results are based on those of retrospective observational studies. CONCLUSIONS: The results obtained were consistent with previously published systematic reviews. The analysis identified several factors that are associated with place of death. PMID- 26351551 TI - Meta-analysis of cytomegalovirus seroprevalence in volunteer blood donors and healthy subjects in Iran from 1992 to 2013. AB - OBJECTIVES: Human cytomegalovirus (CMV), a double-strand DNA herpesvirus, can be transmitted via blood transfusion which is especially important for immunocompromised recipients and can cause a fatal infection. CMV seroprevalence in Iran was studied on blood donors, healthy subjects, and some patients. Highly variable rates were detected. The purpose of this study was to review CMV seroprevalence in blood donors and apparently healthy individuals, in Iran. MATERIALS AND METHODS: One hundred and fifty-eight electronic and paper-based resources and databases including published articles in internal and external journals, seminars, dissertations, and theses available in the database and different websites were used to be systematically reviewed as a meta-analysis. Less related articles to the issue, papers of specific high risk population, and articles with not enough information, were excluded. Eventually 22 articles that satisfied our selection criteria were systematically reviewed and analyzed. To explore heterogeneity between studies the I square (I(2)) index was used. Data were analyzed using the statistical software package (STATA) 11. RESULTS: The heterogeneity between selected studies was 97% with an I(2) statistic. In this study a random effects model was used for meta-analysis. The prevalence of CMV IgG and CMV IgM antibodies in the country were estimated to be 92% (95% CI: 90 94) and 2.6% (95% CI: 1.7-3.6), respectively. CONCLUSION: Given high rate of CMV seropositivity in Iran, it seems that CMVAbs screening would not be a reasonable and affordable approach to prevent CMV infection via transfusion especially for immune compromised recipients, so alternative strategies should be considered. PMID- 26351552 TI - Quercetin induces cell cycle arrest and apoptosis in CD133(+) cancer stem cells of human colorectal HT29 cancer cell line and enhances anticancer effects of doxorubicin. AB - OBJECTIVES: The colorectal cancer stem cells (CSCs) with the CD133(+) phenotype are a rare fraction of cancer cells with the ability of self-renewal, unlimited proliferation and resistance to treatment. Quercetin has anticancer effects with the advantage of exhibiting low side effects. Therefore, we evaluated the anticancer effects of quercetin and doxorubicin (Dox) in HT29 cancer cells and its isolated CD133(+) CSCs. MATERIALS AND METHODS: The CSCs from HT29 cells were isolated using CD133 antibody conjugated to magnetic beads by MACS. Anticancer effects of quercetin and Dox alone and in combination on HT29 cells and CSCs were evaluated using MTT cytotoxicity assay and flow cytometry analysis of cell cycle distribution and apoptosis induction. RESULTS: The CD133(+) CSCs comprised about 10% of HT29 cells. Quercetin and Dox alone and in combination inhibited cell proliferation and induced apoptosis in HT29 cells and to a lesser extent in CSCs. Quercetin enhanced cytotoxicity and apoptosis induction of Dox at low concentration in both cell populations. Quercetin and Dox and their combination induced G2/M arrest in the HT29 cells and to a lesser extent in CSCs. CONCLUSION: The CSCs were a minor population with a significantly high level of drug resistance within the HT29 cancer cells. Quercetin alone exhibited significant cytotoxic effects on HT29 cells and also increased cytoxicity of Dox in combination therapy. Altogether, our data showed that adding quercetin to Dox chemotherapy is an effective strategy for treatment of both CSCs and bulk tumor cells. PMID- 26351553 TI - The effect of silver nanoparticles on apoptosis and dark neuron production in rat hippocampus. AB - OBJECTIVES: Silver nanoparticles (Ag-NPs) are used widely in bedding, water purification, tooth paste and toys. These nanoparticles can enter into the body and move into the hippocampus. The aim of this study was to investigate the neurotoxicity of silver nanoparticles in the adult rat hippocampus. MATERIALS AND METHODS: 12 male Wistar rats were randomly divided into two experimental and control groups (6 rats in each group). Animals in the experimental group received Ag-NPs (30 mg/kg) orally (gavage) for 28 consecutive days. Control group in the same period was treated with distilled water via gavage. At the end of experiment, animals were deeply anesthetized, sacrificed, and their brains were collected from each group. Finally the brain sections were stained using toluidine blue and TUNEL. Then to compare the groups, dark neurons (DNs) and apoptotic neurons were counted by morphometric method. RESULTS: Results showed that the numbers of DNs and apoptotic cells in the CA1, CA2, CA3, and dentate gyrus (DG) of hippocampus significantly increased in the Ag-NPs group in comparison to the control group (P<0.05). CONCLUSION: Exposure to Ag-NPs can induce dark neuron and apoptotic cells in the hippocampus. PMID- 26351554 TI - Mutation analysis of the phenylalanine hydroxylase gene in Azerbaijani population, a report from West Azerbaijan province of Iran. AB - OBJECTIVES: Phenylketonuria (PKU) is a genetic inborn error of phenylalanine (Phe) metabolism resulting from insufficiency in the hepatic enzyme, phenylalanine hydroxylase (PAH), which leads to elevated levels of Phe in the blood. The present study was carried out for mutation analysis of the PAH gene in West Azerbaijan province of Iran. MATERIALS AND METHODS: A total of 218 alleles from 40 PKU families were studied using restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR) method. RESULTS: The frequencies of IVS10 11, S67P, R261Q, R252W, IVS11nt-1 g>c, R408Q, and Q232Q mutations were 28(35), 17(21.25), 15(18.75), 3(3.75), 3(3.75), 2(2.5), and 1(1.25), in cases group, and 51(23.4), 31(14.2), 27(12.4), 6(2.75), 6(2.75), 4(1.83), and 2(0.92) in total group, respectively. The mutations of R243Q, 364delG, L333F, 261X, I65T, and R408W were not detected in our samples. CONCLUSION: It can be concluded that the IVS10-11 mutation has the highest frequency in the tested population. To our knowledge, this report is the first in its own kind and provides better understanding of the genetic heterogeneity, the origin and distributions of PAH mutations in West Azerbaijan province of Iran. PMID- 26351555 TI - The anti-inflammatory effects of venlafaxine in the rat model of carrageenan induced paw edema. AB - OBJECTIVES: Recently anti-inflammatory effects of antidepressants have been demonstrated. Venlafaxine belongs to newer antidepressants with serotonin norepinephrine reuptake inhibition property. The pain alleviating properties of venlafaxine in different pain models such as neurogenic pain, diabetic neuropathy, and fibromyalgia have been demonstrated. Anti-inflammatory effects of venlafaxine and also its underlying mechanisms remain unclear. The present study was designed to evaluate the anti-inflammatory effects of venlafaxine and determine possible underlying mechanisms. MATERIALS AND METHODS: We examined the anti-inflammatory effects of intraperitoneal (IP) and intracerebroventricular (ICV) administration of venlafaxine in the rat model of carrageenan-induced paw edema. RESULTS: Our results showed that both IP (50 and 100 mg/kg) and ICV (50 and 100 MUg/rat) injection of venlafaxine inhibited carrageenan-induced paw edema. Also IP and ICV administration of venlafaxine significantly decreased myeloperoxidase (MPO) activity and interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha production. Finally, we tried to reverse the anti-inflammatory effect of venlafaxine by yohimbine (5 mg/kg, IP), an alpha2-adrenergic antagonist. Our results showed that applied antagonist failed to change the anti inflammatory effect of venlafaxine. CONCLUSION: These results demonstrated that venlafaxine has potent anti-inflammatory effect which is related to the peripheral and central effects of this drug. Also we have shown that anti inflammatory effect of venlafaxine is mediated mostly through the inhibition of IL-1beta and TNF-alpha production and decreases MPO activity in the site of inflammation. PMID- 26351556 TI - FMF Genotype-phenotype correlation in Iranian Azeri Turks: Association between M694V/R761H mutation and amyloidosis. AB - OBJECTIVES: Familial Mediterranean fever (FMF), an inherited autosomal recessive disorder, is frequently present among individuals of Mediterranean origin. Differences in the clinical manifestations of FMF between different ethnic groups have been documented. The aim of the present study was to determine the most common characteristics of FMF and the relationship between clinical findings and the most common mutant alleles of the MEFV gene in an Iranian Azeri Turk population. MATERIALS AND METHODS: We analyzed clinical and genetic data from 415 patients identified as having FMF clinical symptoms and who were referred to the Molecular Genetics Laboratory of Tabriz/Iran over the last 3 years. The mutation type and clinical characteristics were determined for each patient. RESULTS: The following primary clinical characteristics of the patients were observed peritonitis was observed in 378 (93.8%), high-grade fever in 351 (86.88%), arthritis in 215 (54.57%), pleuritis in 207 (53.49%), myalgia in 153 (41.69%), AA amyloidosis in 149 (40.16%), and erysipelas-like erythema in 54 (14.96%) subjects. A positive response to colchicines treatment was noted in 374 (95.1%) patients including 303 patients with two mutated alleles and 71 patients with one identified mutation. CONCLUSION: In contrast to previous studies, there was no significant association between M694V mutation and development of amyloidosis. The M680I/M680I, M680I, M694I, and M694V/R761H genotypes were found to be associated with the development of amyloidosis. These results indicate that physicians need to pay careful attention to patients with asymptomatic or mildly symptomatic FMF with these genotypes. PMID- 26351557 TI - Effect of acetylcholine receptors on the pain-related electrical activities in the hippocampal CA3 region of morphine-addicted rats. AB - OBJECTIVES: To determine the effect of acetylcholine (ACh), pilocarpine, and atropine on pain evoked responses of pain excited neurons (PEN) and pain inhibited neurons (PIN) in hippocampal CA3 region of morphine addicted rats. MATERIALS AND METHODS: Female Wistar rats, weighing between 230-260 g were used in this study. Morphine addicted rats were generated by subcutaneous injection of increasing concentrations of morphine hydrochloride for six days. Trains of electrical impulses applied to the sciatic nerve were used as noxious stimulation and the evoked electrical activities of PEN or PIN in hippocampal CA3 area were recorded using extracellular electrophysiological recording techniques in hippocampal slices. The effect of acetylcholine receptor stimulation by ACh, the muscarinic agonist pilocarpine, and the muscarinic antagonist atropine on the pain evoked responses of pain related electrical activities was analyzed in hippocampal CA3 area of morphine addicted rats. RESULTS: Intra-CA3 microinjection of ACh (2 MUg/1 MUl) or pilocarpine (2 MUg/1 MUl) decreased the discharge frequency and prolonged the firing latency of PEN, but increased the discharge frequency and shortened the firing inhibitory duration (ID) of PIN. The intra-CA3 administration of atropine (0.5 MUg/1 MUl) produced opposite effect. The peak activity of cholinergic modulators was 2 to 4 min later in morphine addicted rats compared to peak activity previously observed in normal rats. CONCLUSION: ACh dependent modulation of noxious stimulation exists in hippocampal CA3 area of morphine addicted rats. Morphine treatment may shift the sensitivity of pain related neurons towards a delayed response to muscarinergic neurotransmission in hippocampal CA3 region. PMID- 26351558 TI - Calcitriol modulates the effects of bone marrow-derived mesenchymal stem cells on macrophage functions. AB - OBJECTIVES: Some evidence showed that calcitriol has an important role in regulating growth and differentiation of mesenchymal stem cells (MSCs). However, the interaction between mesenchymal stem cells and macrophage is not clear yet. The current study was done to investigate the in vitro effects of calcitriol on the interactions between bone marrow-derived MSCs and rat macrophages. MATERIALS AND METHODS: MSCs were isolated from rat bone marrow and pulsed with different concentrations of calcitriol (50, 100 and 200 nanomolar) for 24, 48 and 72 hr. Then, mesenchymal stem cells were co-cultured with macrophages for 4 hr. Finally, macrophages were evaluated for ability to uptake neutral red, phagocytosis activity against opsonized yeast, respiratory burst and viability. RESULTS: Our data showed that bone marrow-derived MSCs pulsed with calcitriol may cause a significant increase in uptake of neutral red and phagocytic activity of opsonized heat killed baker's yeast. Moreover, treatment of MSCs with calcitriol enhanced macrophage viability. Nevertheless, the respiratory burst of macrophages was significantly reduced in macrophages co-cultured with calcitriol-treated MSCs compared to control group. CONCLUSION: Calcitriol may accelerate and potentiate anti-inflammatory M2 macrophage polarization by MSCs. PMID- 26351559 TI - Ultraviolet B efficacy in improving antileishmanial effects of silver nanoparticles. AB - OBJECTIVES: Cutaneous Leishmaniasis (CL) is a parasitic disease caused by various species of the flagellated protozoan, Leishmania. Regardless of the numerous studies, there are still serious challenges in the treatment of CL. This study aimed at evaluating the influence of a low dose ultraviolet B (UVB) radiation along with silver nanoparticles (AgNPs) on a mouse model of CL induced by Leishmania major. MATERIALS AND METHODS: L. major promastigotes (MRHO/IR/75/ER) were extracted from infected mice spleens. Two months after subcutaneous injection of 2*10(6) promastigotes into the footpad of BALB/c mice, when the lesions were developed, the animals were divided into 4 groups including one control group and three study groups: AgNPs, UVB and UVB plus AgNPs. Spleen parasite burden was assessed on day 40 after the first treatment. The data were analyzed by Instat, Elida and SPSS 16 software programs. RESULTS: The results showed the highest pronounced inhibitory effect in the group receiving AgNPs plus UVB. In addition, a significant difference was obtained between the group receiving AgNPs alone and the one with combinational therapy. The findings on parasite burden showed a significant difference between the control group and other treatment groups. CONCLUSION: It could be suggested that UVB in the presence of AgNPs, by inhibiting the spread of CL lesions and reducing the rate of visceral progression of the disease, provides a serious anti-leishmanial effect. PMID- 26351560 TI - HPV18 E7 induces the over-transcription of eIF4E gene in cervical cancer. AB - OBJECTIVES: Eukaryotic translation initiation factor 4E (eIF4E) is overexpressed in cervical cancer (CC). However, the molecular mechanisms are unclear. This study aimed to investigate the molecular mechanism of eIF4E gene overexpression in CC. MATERIALS AND METHODS: The human papillomavirus (HPV) type 18 E7 and eIF4E mRNAs were measured following knock down or overexpression of E7 gene by RT-PCR and real-time PCR. Cell counting kit-8 assay was used to determine the cell proliferation. Flow cytometry was used to analyze the cell cycle and apoptosis. Transwell system was employed to determine the cell migration. RESULTS: Overexpression of E7 gene increased eIF4E mRNA level by 24.3% (P<0.01) in HPV negative C33A cells. Knock down of E7 decreased markedly eIF4E mRNA by 73% (P<0.01) in HPV18 positive HeLa cells. Under the state of high expression of E7, 1) up-regulation of eIF4E drastically promoted the cell proliferation, cell cycle and cell migration, and inhibited the cell apoptosis. 2) down-regulation of eIF4E significantly inhibited the cell proliferation, cell cycle and the ability of cell migration, and also promoted the apoptosis of cervical cancer cells. CONCLUSION: HPV E7 induced eIF4E gene over transcription which might be a new marker for CC. The finding broadens the understanding of the CC carcinogenesis. PMID- 26351561 TI - The correlation between telomerase activity and Bax/Bcl-2 ratio in valproic acid treated MCF-7 breast cancer cell line. AB - OBJECTIVES: Valproic acid (VPA), a drug used in the treatment of neurological disorders, has been shown to have cytotoxic effects on cancer cells through different mechanisms. Telomerase, a ribonucleoprotein reverse transcriptase, is responsible for elongation of the telomere and is activated in cancers. A relation between telomerase activity and resistance to apoptosis has been established. This study focused on probable effects of VPA on MCF-7 cancer cells. In particular, we investigated VPA effects on viability, apoptosis and telomerase activity. MATERIALS AND METHODS: Cytotoxicity effects of VPA on MCF-7 cells were determined by neutral red uptake assay. Cells were treated with different concentrations of VPA (0-32 mM) and telomerase activity and Bax and Bcl-2 protein levels were determined using TRAP assay (PCR-ELISA) method and ELISA method, respectively. RESULTS: The cytotoxic effects of different concentration of VPA on MCF-7 cells were observed as a reduction in cell viability and telomerase activity and altered expression of Bcl-2 family protein levels. The results also showed that there is a significant correlation between reduction of telomerase activity and increase in Bax/Bcl-2 ratio (P=0.001). CONCLUSION: Our study demonstrated that cell viability of MCF-7 cells was decreased after treatment with VPA, probably through a reduction of telomerase activity and an increase in Bax/bcl-2 ratio. Therefore, it could be concluded that VPA is a potent anti cancer agent for breast cancer cells through inhibition of telomerase activity and induction of apoptosis. PMID- 26351562 TI - MiR-125b inhibits stromal cell proliferation in giant cell tumor of bone by targeting parathyroid hormone 1 receptor. AB - OBJECTIVES: miR-125b has been identified as a tumor suppressor in many tumors, but its role in giant cell tumor (GCT) of bone remains poorly understood. The current study aimed to investigate the potential role and mechanism of miR-125b in GCT. MATERIALS AND METHODS: Expression levels of miR-125b in GCT tissues were determined using RT-PCR. The cell proliferation was surveyed by direct cell counting, MTS and CCK-8, and the apoptotic cells were evaluated by Annexin V-FITC and propidium iodine staining assay. The target gene expression was determined using RT-PCR and western blot. Parathyroid hormone 1 receptor (PTH1R) 3'-UTR was cloned into luciferase reporter plasmid to confirm direct targeting. RESULTS: We found that miR-125b was significantly down-regulated in GCT tissues. Using both gain- and loss-of-function analyses, we further revealed that miR-125b suppressed GCT stromal cell proliferation and induced cell apoptosis. Furthermore, we revealed that PTH/PTHrP type 1 receptor is a direct and functional target of miR 125b. CONCLUSION: Our results suggest that miR-125b acts as a tumor suppressor through suppression of the PTH1R/RANKL signaling pathway. These findings contribute to our understanding of the functions of miR-125b in GCT. PMID- 26351563 TI - Evaluation of the effect of physical variables on in vitro release of diclofenac pellets using Box-Behnken design. AB - OBJECTIVES: A Box-Behnken design was used for evaluation of Eudragit coated diclofenac pellets. The purpose of this work was to optimize diclofenac pellets to improve the physicochemical properties using experimental design. MATERIALS AND METHODS: Diclofenac was loaded onto the non-pareil beads using conventional coating pan. Film coating of pellets was done at the same pan. The effect of plasticizer level, curing temperature and curing time was determined on the release of diclofenac from pellets coated with polymethacrylates. RESULTS: Increasing the plasticizer in the coating formula led to decrease in drug release and increasing the curing temperature and time resulted in higher drug release. The optimization process generated an optimum of 35% drug release at 3 hr. The level of plasticizer concentration, curing temperature and time were 20% w/w, 55 degrees C and 24 hr, respectively. CONCLUSION: This study showed that by controllinig the physical variables optimum drug release were obtained. PMID- 26351564 TI - Effects of silymarin on neuropathic pain and formalin-induced nociception in mice. AB - OBJECTIVES: Based on the previous reports, silymarin can suppress nitric oxide, prostaglandin E2 (PGE2), leukotrienes, cytokines production, and neutrophils infiltration. Regarding the fact that inflammation plays an important role in neuropathic and formalin-induced pain, it was assumed that silymarin could reduce pain. The present study investigates the analgesic effects of silymarin in chemical nociception and a model of neuropathic pain. MATERIALS AND METHODS: Chemical nociception was produced by injection of 20 ul of formalin (0.5% formaldehyde in saline) into the plantar region of the right hind paw. A sciatic nerve ligated mouse was applied as the model of neuropathic pain and the antinociceptive response of silymarin was examined 14 days after unilateral nerve ligation using the hot plate test. RESULTS: The intraperitoneal administration of silymarin (25, 50, and, 100 mg/kg) 2 hr prior to the intraplantar formalin injection suppressed the nociceptive response during the late phase of the formalin test significantly, but it was not in a dose-dependent manner. Different doses of silymarin 14 days after unilateral sciatic nerve ligation in hot plate test did not induce obvious antinociception. CONCLUSION: Results of the present study indicated that repeated administration of silymarin prevents the formalin induced nociceptive behavior. However, it is not effective in the treatment of sciatic neuropathic pain. PMID- 26351565 TI - Sensitivity of two methods to detect Mycoplasma agalactiae in goat milk. AB - BACKGROUND: Laboratory diagnostic techniques able to detect Mycoplasma agalactiae are essential in contagious agalactia in dairy goats. This study was designed: 1) to determine the detection limits of PCR and culture in goat milk samples, 2) to examine the effects of experimental conditions including the DNA extraction method, PCR technique and storage conditions (fresh versus frozen stored milk samples) on these methods and 3), to establish agreement between PCR and culture techniques using milk samples from goats with mastitis in commercial dairy herds. The study was conducted both on artificially inoculated and field samples. RESULTS: Our findings indicate that culture is able to detect M. agalactiae in goat milk at lower concentrations than PCR. Qualitative detection of M.agalactiae by culture and PCR was not affected by sample freezing, though the DNA extraction method used significantly affected the results of the different PCR protocols. When clinical samples were used, both techniques showed good agreement. CONCLUSIONS: The results from this study indicate that both culture and PCR are able to detect M. agalactiae in clinical goat mastitis samples. However, in bulk tank milk samples with presumably lower M. agalactiae concentrations, culture is recommended within the first 24 h of sample collection due to its lower limit of detection. To improve the diagnostic sensitivity of PCR in milk samples, there is a need to increase the efficiency of extracting DNA from milk samples using protocols including a previous step of enzymatic digestion. PMID- 26351566 TI - Tentacle: distributed quantification of genes in metagenomes. AB - BACKGROUND: In metagenomics, microbial communities are sequenced at increasingly high resolution, generating datasets with billions of DNA fragments. Novel methods that can efficiently process the growing volumes of sequence data are necessary for the accurate analysis and interpretation of existing and upcoming metagenomes. FINDINGS: Here we present Tentacle, which is a novel framework that uses distributed computational resources for gene quantification in metagenomes. Tentacle is implemented using a dynamic master-worker approach in which DNA fragments are streamed via a network and processed in parallel on worker nodes. Tentacle is modular, extensible, and comes with support for six commonly used sequence aligners. It is easy to adapt Tentacle to different applications in metagenomics and easy to integrate into existing workflows. CONCLUSIONS: Evaluations show that Tentacle scales very well with increasing computing resources. We illustrate the versatility of Tentacle on three different use cases. Tentacle is written for Linux in Python 2.7 and is published as open source under the GNU General Public License (v3). Documentation, tutorials, installation instructions, and the source code are freely available online at: http://bioinformatics.math.chalmers.se/tentacle. PMID- 26351567 TI - UK adults' implicit and explicit attitudes towards obesity: a cross-sectional study. AB - BACKGROUND: Anti-fat attitudes may lead to stigmatisation of and lowered self esteem in obese people. Examining anti-fat attitudes is warranted given that there is an association with anti-fat behaviours. Previous studies, mainly outside the UK, have demonstrated that anti-fat attitudes are increasing over time. METHODS: The study was cross-sectional with a sample of 2380 participants (74.2 % female; aged 18-65 years). In an online survey participants reported demographic characteristics and completed a range of implicit and explicit measures of obesity related attitudes. RESULTS: Perceptions of obesity were more negative than reported in previously. Main effects indicated more negative perceptions in males, younger respondents and more frequent exercisers. Attitudes about obesity differed in relation to weight category, and in general were more positive in obese than non-obese respondents. CONCLUSIONS: This is the first study to demonstrate anti-fat attitudes across different sections of the UK population. As such, this study provides the first indication of the prevalence of anti-fat attitudes in UK adults. Interventions to modify these attitudes could target specific groups of individuals with more negative perceptions as identified here. Future work would be useful that increases understanding of both implicit and explicit attitudes towards obesity. PMID- 26351568 TI - Comorbidity burden at dialysis initiation and mortality: A cohort study. AB - BACKGROUND: A high level of comorbidity at dialysis initiation is associated with an increased risk of death. However, contemporary assessments of the validity and prognostic value of comorbidity indices are lacking. OBJECTIVES: To assess the validity of two comorbidity indices and to determine if a high degree of comorbidity is associated with mortality among dialysis patients. DESIGN: Cohort study. SETTING: QEII Health Sciences Centre (Halifax, Nova Scotia, Canada). PATIENTS: Incident, chronic dialysis patients between 01 Jan 2006 and 01 Jul 2013. MEASUREMENTS: EXPOSURE: The Charlson Comorbidity Index (CCI) and End-Stage Renal Disease Comorbidity Index (ESRD-CI) were used to classify individual comorbid conditions into an overall score. Comorbidities were classified using patient charts and electronic records. OUTCOME: All-cause mortality. Confounders: Patient demographics, dialysis access, cause of ESRD and baseline laboratory data. METHODS: Regression coefficients were estimated on the CCI and ESRD-CI. Discrimination for death was assessed using Harrell's c-index. Adjusted Cox proportional hazard models were used to calculate relative hazards and 95 % confidence intervals for each category of the CCI and ESRD-CI. RESULTS: The cohort consisted of 771 ESRD patients from 01 Jan 2006 to 01 Jul 2013. Most were male (62 %) and Caucasian (91 %). The cohort had a high proportion of diabetes (48 %), history of previous myocardial infarction (31 %) and heart failure (22 %). Regression coefficients on the CCI and ESRD-CI were 0.55 and 0.52, respectively. The c-index, for the prediction of death, was 0.61 for the CCI and 0.63 for the ESRD-CI. ESRD-CI scores of 4, 5 and >=6 were associated with a similar mortality risk (adjusted relative hazard of 1.95, 1.89 and 1.99, respectively). There was a small increased mortality risk for CCI scores of 4, 5 and >=6 (adjusted relative hazard of 1.86, 2.38 and 2.71, respectively). LIMITATIONS: Classification of comorbidities for each patient was determined by clinical impression. CONCLUSIONS: The CCI and ESRD-CI have a limited ability to discriminate mortality risk for incident dialysis patients. Acknowledging the frequency with which they are used, this study emphasizes the need to re-examine the usefulness of previously derived comorbidity indices in contemporary dialysis cohorts. PMID- 26351569 TI - Analysis of the Retinal Nerve Fiber Layer in Retinitis Pigmentosa Using Optic Coherence Tomography. AB - Aim. To evaluate the peripapillary retinal nerve fiber layer (RNFL) changes in retinitis pigmentosa (RP) patients using spectral domain optic coherence tomography (Sd-OCT). Methods. We retrospectively examined medical records of forty-four eyes of twenty-two RP patients. The results were also compared with those of previously reported forty-four eyes of twenty-two normal subjects (controls). Records of average and four quadrants peripapillary RNFL thickness measurements using Sd-OCT were assessed. Results. In RP patients the mean RNFL thickness was 97.57 +/- 3.21 MUm. The RNFL in the superior, temporal, nasal, and inferior quadrants was 119.18 +/- 4.47 MUm, 84.68 +/- 2.31 MUm, 75.09 +/- 3.34 MUm, and 113.88 +/- 4.25 MUm, respectively. While the thinning of RNFL was predominantly observed in the inferior quadrant, the thickening was mostly noted in temporal quadrant. The differences between mean, superior, and nasal quadrant RNFL thicknesses were not statistically significant when compared with control group. The RP patients had thinner inferior quadrant and thicker temporal quadrant than control group (p < 0.05). Conclusion. Sd-OCT is highly sensitive and effective instrument to detect RNFL changes in RP patients. RNFL measurements can provide information about the progression of retinitis pigmentosa and may provide prognostic indices for future treatment modalities. PMID- 26351570 TI - Graves' Ophthalmopathy: VISA versus EUGOGO Classification, Assessment, and Management. AB - Graves' ophthalmopathy (GO) is an autoimmune inflammatory disorder associated with thyroid disease which affects ocular and orbital tissues. GO follows a biphasic course in which an initial active phase of progression is followed by a subsequent partial regression and a static inactive phase. Although the majority of GO patients have a mild, self-limiting, and nonprogressive ocular involvement, about 3-7% of GO patients exhibit a severe sight-threatening form of the disease due to corneal exposure or compressive optic neuropathy. An appropriate assessment of both severity and activity of the disease warrants an adequate treatment. The VISA (vision, inflammation, strabismus, and appearance), and the European Group of Graves' Orbitopathy (EUGOGO) classifications are the two widely used grading systems conceived to assess the activity and severity of GO and guide the therapeutic decision making. A critical analysis of classification, assessment, and management systems is reported. A simplified "GO activity assessment checklist" for routine clinical practice is proposed. Current treatments are reviewed and management guidelines according to the severity and activity of the disease are provided. New treatment modalities such as specific monoclonal antibodies, TSH-R antagonists, and other immunomodulatory agents show a promising outcome for GO patients. PMID- 26351571 TI - Preservation of the Photoreceptor Inner/Outer Segment Junction in Dry Age-Related Macular Degeneration Treated by Rheohemapheresis. AB - Aim. To evaluate the long-term effect of rheohemapheresis (RHF) treatment of age related macular degeneration (AMD) on photoreceptor IS/OS junction status. Methods. In our study, we followed 24 patients with dry AMD and drusenoid retinal pigment epithelium detachment (DPED) for a period of more than 2.5 years. Twelve patients (22 eyes) were treated by RHF and 12 controls (18 eyes) were randomized. The treated group underwent 8 RHF standardized procedures. We evaluated best corrected visual acuity, IS/OS junction status (SD OCT), and macular function (multifocal electroretinography) at baseline and at 2.5-year follow-up. Results. RHF caused a decrease of whole-blood viscosity/plasma viscosity at about 15/12%. BCVA of treated patients increased insignificantly (P = 0.187) from median 74.0 letters (56.2 to 81.3 letters) to median 79.0 letters (57.3 to 83.4 letters), but it decreased significantly from 74.0 letters (25.2 to 82.6 letters) to 72.5 letters (23.4 to 83.1 letters) in the control group (P = 0.041). The mfERG responses in the region of eccentricity between 1.8 degrees and 7 degrees were significantly higher in treated patients (P = 0.04). Conclusions. RHF contributed to sparing of photoreceptor IS/OS junction integrity in the fovea, which is assumed to be a predictive factor for preservation of visual acuity. PMID- 26351572 TI - Childbearing May Increase the Risk of Nondiabetic Cataract in Chinese Women's Old Age. AB - Backgrounds. Ocular changes may arise during pregnancy and after childbirth, but very few studies have reported the association between childbearing and cataract among older adults. Methods. 14,292 individuals aged 60+ years were recruited in Xiamen, China, in 2013. Physician-diagnosed cataract and diabetes status were assessed by a self-reported questionnaire. Childbearing status was measured by number of children (NOC). Structural equation modeling (SEM) analysis was conducted to examine the relationships among NOC, diabetes, and cataract. Gender specific logistic models regressing nondiabetic cataract on NOC were performed by adjusting some covariates. Results. 14,119 participants had complete data, of whom 5.01% suffered from cataract, with higher prevalence in women than men (6.41% versus 3.51%). Estimates of SEM models for women suggested that both NOC and diabetes were risk factors for cataract and that no correlation existed between NOC and diabetes. Women who had one or more children faced roughly 2-4 times higher risk of nondiabetic cataract than their childless counterparts (OR [95% CI] = 3.88 [1.24, 17.71], 3.21 [1.04, 14.52], 4.32 [1.42, 19.44], 4.41 [1.46, 19.74], and 3.98 [1.28, 18.10] for having 1, 2, 3, 4-5, and 6 or more children, resp.). Conclusions. Childbearing may increase the risk of nondiabetic cataract in Chinese women's older age. PMID- 26351573 TI - Effects of Laser Peripheral Iridotomy in Subgroups of Primary Angle Closure Based on Iris Insertion. AB - Purpose. To investigate the effect of laser peripheral iridotomy (LPI) in subgroups of primary angle closure based on iris insertion configuration. Methods. Anterior segment optical coherence tomography (AS-OCT) images were obtained before and two weeks after LPI. Qualitative classification of angle closure eyes according to iris insertion (basal insertion group (BG) and nonbasal insertion group (NBG)) was performed. Anterior chamber depth (ACD), lens vault (LV), iris curvature, iris area, iris thickness (IT750), and angle opening distance (AOD750) 750 microns from scleral spur were calculated. Uni- and multivariate regression analysis was carried out to evaluate factors associated with AOD750 before and after LPI. Results. Ninety-two eyes of 92 subjects were categorized as NBG (39 eyes) or BG (53 eyes). The mean change after LPI was not significantly different between two groups in all parameters. In both groups, AOD750 was affected by ACD (p < 0.001, p = 0.044) before LPI. AOD750 was affected by LV (p = 0.012) in NBG, but by ACD (p < 0.001) and IT750 (p = 0.039) in BG after LPI. Conclusions. The outcomes of LPI are not significantly different between angle closure subgroups with different iris insertions. However, factors affecting AOD750 show differences between two subgroups after LPI. PMID- 26351574 TI - Factors Affecting Cirrus-HD OCT Optic Disc Scan Quality: A Review with Case Examples. AB - Spectral-domain OCT is an established tool to assist clinicians in detecting glaucoma and monitor disease progression. The widespread use of this imaging modality is due, at least in part, to continuous hardware and software advancements. However, recent evidence indicates that OCT scan artifacts are frequently encountered in clinical practice. Poor image quality invariably challenges the interpretation of test results, with potential implications for the care of glaucoma patients. Therefore, adequate knowledge of various imaging artifacts is necessary. In this work, we describe several factors affecting Cirrus HD-OCT optic disc scan quality and their effects on measurement variability. PMID- 26351575 TI - Characterization of Visual Symptomatology Associated with Refractive, Accommodative, and Binocular Anomalies. AB - Purpose. To characterize the symptomatology of refractive, accommodative, and nonstrabismic binocular dysfunctions and to assess the association between dysfunctions and symptoms. Methods. 175 randomised university students were examined. Subjects were given a subjective visual examination with accommodative and binocular tests, evaluating their symptomatology. Accommodative and binocular dysfunctions (AD, BD) were diagnosed according to the number of existing clinical signs: suspect AD or BD (one fundamental clinical sign), high suspect (one fundamental + 1 complementary clinical sign), and definite (one fundamental + 2 or more complementary clinical signs). A logistic regression was conducted in order to determine whether there was an association between dysfunctions and symptoms. Results. 78 subjects (44.6%) reported any kind of symptoms which were grouped into 18 categories, with "visual fatigue" being the most frequent (20% of the overall complaints). Logistic regression adjusted by the presence of an uncorrected refractive error showed no association between any grade of AD and symptoms. Subjects with BD had more likelihood of having symptoms than without dysfunction group (OR = 3.35), being greater when only definite BD were considered (OR = 8.79). Conclusions. An uncorrected refractive error is a confusion factor when considering AD symptomatology. For BD, the more the number of clinical signs used the greater the likelihood suffering symptoms. PMID- 26351576 TI - Immediate Sequential Bilateral Cataract Surgery: A Systematic Review and Meta Analysis. AB - The aim of the present systematic review was to examine the benefits and harms associated with immediate sequential bilateral cataract surgery (ISBCS) with specific emphasis on the rate of complications, postoperative anisometropia, and subjective visual function in order to formulate evidence-based national Danish guidelines for cataract surgery. A systematic literature review in PubMed, Embase, and Cochrane central databases identified three randomized controlled trials that compared outcome in patients randomized to ISBCS or bilateral cataract surgery on two different dates. Meta-analyses were performed using the Cochrane Review Manager software. The quality of the evidence was assessed using the GRADE method (Grading of Recommendation, Assessment, Development, and Evaluation). We did not find any difference in the risk of complications or visual outcome in patients randomized to ISBCS or surgery on two different dates. The quality of evidence was rated as low to very low. None of the studies reported the prevalence of postoperative anisometropia. In conclusion, we cannot provide evidence-based recommendations on the use of ISBCS due to the lack of high quality evidence. Therefore, the decision to perform ISBCS should be taken after careful discussion between the surgeon and the patient. PMID- 26351577 TI - Systemic Comorbidity in Children with Cataracts in Nigeria: Advocacy for Rubella Immunization. AB - Background. Congenital and developmental cataracts are leading causes of childhood blindness and severe visual impairment. They may be associated with systemic diseases including congenital heart diseases which are among the major causes of morbidity and mortality in childhood. The pattern of systemic comorbidities seen in children diagnosed with cataract in Calabar, Nigeria, was studied. Methods. A retrospective review was conducted on the children who had cataract surgery between 2011 and 2012. Diagnosis of the systemic condition was documented. Results. A total of 66 children were recruited for the study. Cardiac disease was seen in 26 children (39.9%), followed by delayed milestone in 16 (24.2%), intellectual disability in 14 (21.2%), deafness in 11 (16.7%), epilepsy in 4 (6.1%), and physical handicap in 3 (4.5%) of them. Clinically confirmed Congenital Rubella Syndrome was seen in 30 (45%) of the children. The pattern of CHD seen was as follows: patent ductus arteriosus in 16 (24.2%) followed by ventricular-septal defect in 5 (7.6%), atrial-septal defect in 3 (4.5%), and pulmonary stenosis in 2 (3%). Conclusion. Systemic comorbidities, especially cardiac anomalies, are common among children with cataract in Nigeria. Congenital Rubella Syndrome may be a prominent cause of childhood cataract in our environment. Routine immunization of school girls against rubella is advocated as a measure to mitigate this trend. PMID- 26351578 TI - Preeclampsia Is Associated with Increased Central Aortic Pressure, Elastic Arteries Stiffness and Wave Reflections, and Resting and Recruitable Endothelial Dysfunction. AB - Introduction. An altered endothelial function (EF) could be associated with preeclampsia (PE). However, more specific and complementary analyses are required to confirm this topic. Flow-mediated dilation (FMD), low-flow-mediated constriction (L-FMC), and hyperemic-related changes in carotid-radial pulse wave velocity (PWVcr) offer complementary information about "recruitability" of EF. Objectives. To evaluate, in healthy and hypertensive pregnant women (with and without PE), central arterial parameters in conjunction with "basal and recruitable" EF. Methods. Nonhypertensive (HP) and hypertensive pregnant women (gestational hypertension, GH; preeclampsia, PE) were included. Aortic blood pressure (BP), wave reflection parameters (AIx@75), aortic pulse wave velocity (PWVcf) and PWVcr, and brachial and common carotid stiffness and intima-media thickness were measured. Brachial FMD and L-FMC and hyperemic-related change in PWVcr were measured. Results. Aortic BP and AIx@75 were elevated in PE. PE showed stiffer elastic but not muscular arteries. After cuff deflation, PWVcr decreased in HP, while GH showed a blunted PWVcr response and PE showed a tendency to increase. Maximal FMD and L-FMC were observed in HP followed by GH; PE did not reach significant arterial constriction. Conclusion. Aortic BP and wave reflections as well as elastic arteries stiffness are increased in PE. PE showed both "resting and recruitable" endothelial dysfunctions. PMID- 26351579 TI - Renin-Angiotensin System Genes Polymorphisms and Essential Hypertension in Burkina Faso, West Africa. AB - Objective. This study aimed to investigate the association between three polymorphisms of renin-angiotensin system and the essential hypertension in the population of Burkina Faso. Methodology. This was a case-control study including 202 cases and 204 matched controls subjects. The polymorphisms were identified by a classical and a real-time PCR. Results. The AGT 235M/T and AT1R 1166A/C polymorphisms were not associated with the hypertension while the genotype frequencies of the ACE I/D polymorphism between patients and controls (DD: 66.83% and 35.78%, ID: 28.22% and 50.98%, II: 4.95% and 13.24%, resp.) were significantly different (p < 10(-4)). The genotype DD of ACE gene (OR = 3.40, p < 0.0001), the increasing age (OR = 3.83, p < 0.0001), obesity (OR = 4.84, p < 0.0001), dyslipidemia (OR = 3.43, p = 0.021), and alcohol intake (OR = 2.76, p < 0.0001) were identified as the independent risk factors for hypertension by multinomial logistic regression. Conclusion. The DD genotype of the ACE gene is involved in susceptibility to hypertension. Further investigations are needed to better monitor and provide individualized care for hypertensive patients. PMID- 26351580 TI - Turkish Version of the Cognitive Distortions Questionnaire: Psychometric Properties. AB - Cognitive distortions are interrelated with all layers of cognitions, and they may be part of the treatment once they are accessed, identified, labeled, and changed. From both a research and a clinical perspective, it is of utmost importance to disentangle cognitive distortions from similar constructs. Recently, the Cognitive Distortions Questionnaire (CD-Quest), a brief and comprehensive measure, was developed to assess both the frequency and the intensity of cognitive distortions. The aim of the present study was to assess the psychometric properties of the Turkish version of the CD-Quest in a psychiatric outpatient sample. Demographic and clinical data of the participants were analyzed by descriptive statistics. For group comparisons, Student's t-test was applied. An exploratory principal components factor analysis was performed, followed by an oblique rotation. To assess the internal consistency of the scale Cronbach's alpha was computed. The correlation coefficient was calculated for test-retest reliability over a 4-week period. For concurrent validity, bivariate Pearson correlation analyses were conducted with the measures of mood severity and negatively biased cognitions. The results revealed that the scale had excellent internal consistency, good test-retest reliability, unidimensional factor structure, and evidence of concurrent and discriminant validity. PMID- 26351581 TI - Radiofrequency for the Treatment of Lumbar Radicular Pain: Impact on Surgical Indications. AB - Study Design. Quasiexperimental study. Objective. To investigate whether radiofrequency treatment can preclude the need for spinal surgery in both the short term and long term. Background. Radiofrequency is commonly used to treat lumbosacral radicular pain. Only few studies have evaluated its effects on surgical indications. Methods. We conducted a quasiexperimental study of 43 patients who had been scheduled for spinal surgery. Radiofrequency was indicated for 25 patients. The primary endpoint was the decision of the patient to reject spinal surgery 1 month and 1 year after treatment (pulsed radiofrequency of dorsal root ganglion, 76%; conventional radiofrequency of the medial branch, 12%; combined technique, 12%). The primary endpoint was the decision of the patient to reject spinal surgery 1 month and 1 year after treatment. In addition, we also evaluated adverse effects, ODI, NRS. Results. We observed after treatment with radiofrequency 80% of patients rejected spinal surgery in the short term and 76% in the long term. We conclude that radiofrequency is a useful treatment strategy that can achieve very similar outcomes to spinal surgery. Patients also reported a very high level of satisfaction (84% satisfied/very satisfied). We also found that optimization of the electrical parameters of the radiofrequency improved the outcome of this technique. PMID- 26351582 TI - Impaired Fertility Associated with Subclinical Hypothyroidism and Thyroid Autoimmunity: The Danish General Suburban Population Study. AB - INTRODUCTION: The aim of this study was to estimate the significance of TSH, thyroid peroxidase antibody (TPOAb), and mild (subclinical) hypothyroidism in women from The Danish General Suburban Population Study (GESUS) on the number of children born, the number of pregnancies, and the number of spontaneous abortions. METHODS: Retrospective cross sectional study of 11254 women participating in GESUS. Data included biochemical measurements and a self administrated questionnaire. RESULTS: 6.7% had mild (subclinical) hypothyroidism and 9.4% prevalent hypothyroidism. In women with mild hypothyroidism TPOAb was significantly elevated and age at first child was older compared to controls. TSH and TPOAb were negatively linearly associated with the number of children born and the number of pregnancies in the full cohort in age-adjusted and multiadjusted models. TSH or TPOAb was not associated with spontaneous abortions. Mild (subclinical) hypothyroidism was associated with a risk of not having children and a risk of not getting pregnant in age-adjusted and multiadjusted models. Prevalent hypothyroidism was not associated with the number of children born, the number of pregnancies, or spontaneous abortions. CONCLUSION: Impaired fertility is associated with TSH, TPOAb, and mild (subclinical) hypothyroidism in a Danish population of women. PMID- 26351583 TI - Variations in the Root Form and Root Canal Morphology of Permanent Mandibular First Molars in a Sri Lankan Population. AB - The present study was conducted to determine the number of roots and morphology of the root canal system of permanent mandibular first molars (M1) in a Sri Lankan population. Sample of 529 M1 teeth was used. The number of roots was examined and the lengths of the mesial and distal roots were measured to the nearest 0.01 mm. Vacuum injection protocol was used to inject China ink into the root canal system, making it transparent. Root canal morphology was recorded using Vertucci's classification. Presence of furcation canals, position of lateral canals, intercanal communications, level of bifurcation, and convergence of the root canal system were recorded. M1 showed three roots in 4.1% of the sample. Commonest root canal morphology of the mesial root was type IV and the distal root was type I. The level of bifurcation of the root canals was commonly observed in the cervical one-third of the root while convergence was observed in the apical one-third in both roots. Prevalence of three rooted mandibular first molars is less than 5%. Mesial root showed the most variable canal morphology. Prevalence of furcation canals was 1.5% while that of middle mesial canals was 0.2%. PMID- 26351584 TI - Chemical Composition and In Vitro Antibacterial Activity of Mentha spicata Essential Oil against Common Food-Borne Pathogenic Bacteria. AB - The aim of the present study was to investigate chemical composition and antibacterial activity of essential oil from the leaf of Mentha spicata plant against common food-borne pathogenic bacteria (Staphylococcus aureus, Bacillus subtilis, Bacillus cereus, Listeria monocytogenes, Salmonella typhimurium, and Escherichia coli O157:H7). Chemical composition of the essential oil was identified by gas chromatography coupled with mass spectrometer detector (GC-MS). The antibacterial activity of the essential oil was evaluated by broth microdilution method and agar disk diffusion assay. According to the result of GC MS analysis, 18 components were identified, accounting for 99.89% of the whole essential oil. The main components were carvone (78.76%), limonene (11.50%), beta bourbonene (11.23%), cis-dihydrocarveol (1.43%), trans-caryophyllene (1.04%), menthone (1.01%), menthol (1%), and terpinen-4-ol (0.99). The essential oil exhibited moderate level of antibacterial activity against all test microorganisms. In general, Gram-positive bacteria were more susceptible to M. spicata essential oil than Gram-negative bacteria. L. monocytogenes was the most sensitive of the microorganisms to the antibacterial activity of M. spicata essential oil (inhibition zone = 22 mm and MIC and MBC = 2.5 uL/mL). Based on our results, the essential oil of M. spicata plant collected from Kermanshah province, west of Iran, has a potential to be applied as antibacterial agent. PMID- 26351585 TI - Association of Sleep Quality and Waking Time with Prediabetes: The Qazvin Metabolic Diseases Study, Iran. AB - Aims. It is known that sleep has a major role in the regulation of endocrine functions and glucose metabolism. However, it is not clear whether the sleep pattern is affected at or prior to the onset of diabetes, among those with prediabetes. The purpose of this study was to determine the association of sleep patterns and prediabetes in Qazvin, Iran. Methods. A representative sample of residents of Qazvin was selected by multistage cluster random sampling method in 2011. Plasma glucose level and sleep quality were measured cross-sectionally as well as demographic characteristics. A logistic regression analysis was used to examine the association of sleep status and prediabetes. Results. Mean age was 39.3 +/- 10.1 years. Of 958, 474 (49.47%) were female. Poor sleep quality was associated with 2.197-fold increased risk of prediabetes after adjustment for age, gender, body mass index, and metabolic syndrome. Conclusion. This study provides evidences that subjects with poor sleep quality are more likely to develop prediabetes than people with good sleep quality. PMID- 26351586 TI - Paravertebral Block Combined with Sedation for a Myasthenic Patient Undergoing Breast Augmentation. AB - Paravertebral block is a unilateral analgesic technique that can provide adequate surgical anesthesia and great advantages in many types of surgery with a low side effect profile. In this case we present combination of bilateral thoracic paravertebral block under ultrasound guidance with sedation which provides complete anesthesia and postoperative analgesia in a myasthenic patient undergoing cosmetic breast surgery. In myasthenic patients paravertebral blocks may be a better option for breast surgery with avoiding the need for muscle relaxants and opioids and risk of respiratory failure in postoperative period. PMID- 26351587 TI - Mobile Intracardiac Mass after Inguinal Hernia Repair: An Unresolved Treatment Dilemma. AB - Right heart thrombi (RHT) are rare but well-described entity in literature. Their isolation has been considered as confirmatory for the diagnosis of venous thromboembolism (VTE). Even though their isolation aids the diagnosis, physicians are faced with a difficult management dilemma giving the paucity of data to support any treatment decision. We present a case of RHT in an 81-year-old man who presented to hospital with a large mobile right heart thrombus in transit seen on transthoracic echocardiogram (TTE). He was successfully treated with anticoagulation alone. This case highlights the importance of TTE in establishing the diagnosis and describes the interplay of factors influencing treatment decision. PMID- 26351588 TI - Rare Case of Rapidly Worsening REM Sleep Induced Bradycardia. AB - Sinoatrial arrest also known as sinus pause occurs when sinoatrial node of the heart transiently ceases to generate the electrical impulse necessary for the myocardium to contract. It may last from 2.0 seconds to several minutes. Etiologies of sinoatrial arrest can be complex and heterogeneous. During rapid eye movement (REM) sleep, sinus arrests unrelated to apnea or hypopnea are very rare and only a few cases have been reported. Here we report a case of 36-year old male with no significant past medical history who presented to our hospital after a syncopal episode at night. Physical examination showed no cardiac or neurological abnormalities and initial EKG and neuroimaging were normal. Overnight telemonitor recorded several episodes of bradyarrhythmia with sinus arrest that progressively lengthened over time. Sleep study was done which confirmed that sinus arrests occurred more during REM sleep and are unrelated to apnea or hypopnea. Electrophysiology studies showed sinus nodal dysfunction with no junctional escape, subsequently a dual chamber pacemaker placed for rapidly worsening case of REM sleep induced bradycardia. PMID- 26351589 TI - Subclavian Artery Pseudoaneurysm Formation 3 Months after a Game of Rugby Union. AB - Pseudoaneurysms of the subclavian artery remain a rare complication after fracture of the clavicle. We report a case of delayed diagnosis of a subclavian artery pseudoaneurysm after a closed fracture of the clavicle in a 15-year-old patient, 3 months after the original injury while playing rugby union. Despite several attendances to the Emergency Department with vague symptoms, the final diagnosis was confirmed by duplex ultrasound and Computed Tomography of the thorax. Surgical repair was indicated due to acute limb ischaemia from distal embolisation from a large pseudoaneurysm, with the patient making a full recovery. This case highlights the need for clinical vigilance when assessing patients, particularly on repeated occasions when their recovery appears to be impaired. A thorough history and clinical examination can raise suspicion of even rare occurrences and aid prompt management. PMID- 26351590 TI - Novel Therapies for Myocardial Irritability following Extreme Hydroxychloroquine Toxicity. AB - Introduction. Hydroxychloroquine (HCQ) overdose is rare and potentially deadly when consumed in large doses. Management of severe HCQ toxicity is limited and infrequently reported. This report presents the case of a massive ingestion of HCQ. Case Report. A 23-year-old female presents following an intentional ingestion of approximately 40 g of HCQ. Within six hours after ingestion, she developed severe hemodynamic instability resulting from myocardial irritability with frequent ventricular ectopic activity leading to runs of polymorphic ventricular tachycardia (PMVT) and ventricular fibrillation (VF) requiring multiple defibrillations. Additional treatments included intravenous diazepam, epinephrine, norepinephrine, sodium bicarbonate, and magnesium sulfate. Despite the ongoing hemodynamic instability, the patient was also treated with Intralipid (ILE) and received hemodialysis. Improvements in her hemodynamics were observed after 18 hours. She survived her massive overdose of HCQ. Conclusion. HCQ poisoning is rare but serious because of its rapid progression to life threatening symptoms. Hemodynamic support, gastric decontamination, electrolyte monitoring and replacement, and management of arrhythmias are the mainstays of treatment. The combined role of dialysis and ILE in the setting of massive HCQ overdose may improve outcomes. PMID- 26351591 TI - Acute-on-Chronic Kidney Injury in Thyroid Hormone Withdrawal: A Case with Possible Implications for Radioactive Iodine Planning. AB - The association between renal dysfunction and hypothyroidism is of increasing clinical importance as thyroid hormone replacement may attenuate decline in renal function and improve cardiovascular outcomes in patients with chronic kidney disease (CKD). Although multiple mechanisms for the induction of renal insufficiency in hypothyroidism have been described, the renal impact of short term, acute hypothyroidism is unknown, which has possible implications for thyroid cancer patients preparing to receive radioactive iodine (RAI). A 56-year old gentleman with history of unilateral renal agenesis and CKD stage III presented with intermediate-risk papillary thyroid cancer. In preparation for RAI, he underwent thyroid hormone withdrawal (THW) associated with acute kidney injury (AKI), as marked by a decrease in his estimated GFR from 53 to 32 mL/min/1.73 m(2). Upon resumption of thyroid hormone, renal function returned to baseline within months. Although AKI in this case was not otherwise associated with adverse outcome and reversed upon resumption of thyroid hormone, it is possible that this phenomenon could result in potential harm, particularly in the patient with baseline renal insufficiency. In CKD patients, preparation for RAI therapy may require special consideration; future studies should address the role of recombinant TSH to mitigate deleterious renal effects of acute hypothyroidism in this setting. PMID- 26351592 TI - Intestinal Amyloidosis in Common Variable Immunodeficiency and Rheumatoid Arthritis. AB - We present a case of reactive amyloidosis that developed secondary to common variable immunodeficiency and rheumatoid arthritis. A 66-year-old woman, with prior history of common variable immunodeficiency and rheumatoid arthritis, was referred to our clinic for chronic diarrhea investigation. The patient was submitted to colonoscopy with ileoscopy, which did not show relevant endoscopic alterations. However, undertaken biopsies revealed amyloid deposition. Since amyloidosis with GI involvement is a rare cause of chronic diarrhea, this pathology should be considered in etiologic investigation, especially when associated with chronic inflammatory diseases. PMID- 26351593 TI - Superior Mesenteric Artery Syndrome Associated with Rapid Weight Loss Attributed to Amphetamine Abuse. AB - Superior mesenteric artery (SMA) syndrome arises from a reduction in the angle formed between the SMA and the aorta, thereby compressing the third portion of the duodenum. This phenomenon may be caused by a number of factors, one of which being acute weight loss. We report a case of a female patient presenting with abdominal pain and vomiting who developed superior mesenteric artery (SMA) syndrome as a result of rapid weight loss, thought to be secondary to amphetamine abuse. This association can often be overlooked and, to our knowledge, has not been previously reported. PMID- 26351594 TI - Promyelocytic Leukemia with No Retinoic Acid Receptor Alpha Abnormality but with RUNX1T1 Insertion to Chromosome 7q: A Classification and Management Dilemma. AB - A case of acute promyelocytic leukemia (APL) with RUNX1T1 insertion to 7q is described and compared to reported cases of APL with negative retinoic acid receptor alpha (RARA) abnormality. In this report, we describe the case of a 2 year-old boy who presented with bone pain and was found to have pancytopenia. Bone marrow examination showed morphologic and immunophenotypic findings typical of APL, but conventional cytogenetics, fluorescence in situ hybridization (FISH), and real-time polymerase chain reaction (RT-PCR) showed no evidence of RARA rearrangements. The only cytogenetic abnormality found was a small insertion in 7q, and three copies of RUNX1T1. Gene sequencing results became available after initiating therapy but were not informative. We describe the rarity of such cases and discuss how the typical morphologic and immunophenotypic findings of APL, coupled with the definite absence of RARA rearrangement (by FISH and RT-PCR), present a diagnostic and classification dilemma, raising the possibility of an unknown alternative mechanism for the leukemogenesis and maturation arrest seen in other APL variants. The diagnostic challenges and urgent management issues this unusual case raises may justify including it, along with similar cases, in a separate subtype of acute myeloid leukemia (AML) in future classifications. PMID- 26351595 TI - Two Case Presentations Infected by Trichosporon asahii and Treated with Voriconazole Successfully. AB - Background. Trichosporon asahii is an opportunistic fungus that causes infections in immunosuppressed patients. Neutropenia developing due to malignancies is an important risk factor for fungal infection. Case Report. We present two pediatric oncology cases successfully treated with voriconazole after T. asahii infection that is known to cause fatal sepsis and invasive fungal infection. Conclusion. There is no conclusive evidence that the antifungal agent voriconazole is effective in the neutropenic patients infected with Trichosporon asahii. Liposomal amphotericin B has also been reported to be inadequate for treatment. We believe that our patients were successfully treated and survived because the antifungal agents were started early and properly, although the infection can be fatal in up to 80% of cases despite treatment. PMID- 26351596 TI - ESBL E. coli Urosepsis Resulting in Endogenous Panophthalmitis Requiring Evisceration of the Eye in a Diabetic Patient. AB - A primary infection in a remote site resulting in vision threatening complications like panophthalmitis in a person who is not immune-compromised is rare. We report a case of endogenous bilateral bacterial endophthalmitis progressing into panophthalmitis in one eye requiring evisceration of that eye. A patient admitted with severe ESBL E. coli urosepsis was effectively treated with source control (bilateral DJ stenting for hydroureteronephrosis) and antibiotics. She was found to have features suggestive of bilateral conjunctivitis which progressed to panophthalmitis possibly due to delay in appropriate diagnosis and treatment. Diagnosis requires a very high index of suspicion if eye involvement is noted in a patient with features of bacteraemia and early intervention could possibly produce better outcomes. To our knowledge, this is the first case of ESBL E. coli urosepsis complicated by microbiologically confirmed panophthalmitis. PMID- 26351597 TI - Purple Urine Bag Syndrome in Two Elderly Men with Urinary Tract Infection. AB - Purple urine bag syndrome is a rare condition in which purple discoloration of urine inside its collection bag occurs. We describe two illustrative cases. The first patient is an 81-year-old man who was hospitalized for a newly diagnosed lymphoma with acute obstructive renal failure for which a nephrostomy procedure was performed. During the hospitalization, a sudden purple discoloration of the suprapubic catheter urine was noted, while the nephrostomy urine had a normal color. Urine culture from the suprapubic catheter was positive for Pseudomonas aeruginosa and Enterococcus faecalis; urine from the nephrostomy was sterile. The second case is an 80-year-old man who was admitted for heart failure with cardiorenal dilemma and who was started on intermittent hemodialysis. There was a sudden purple discoloration of the urine in the collection bag from his indwelling catheter. He was diagnosed with an E. coli urinary infection and treated with amoxicillin and removal of the indwelling catheter. These two cases illustrate the typical characteristics of purple urine bag syndrome. PMID- 26351598 TI - Minimal Change Disease as a Secondary and Reversible Event of a Renal Transplant Case with Systemic Lupus Erythematosus. AB - Secondary causes of minimal change disease (MCD) account for a minority of cases compared to its primary or idiopathic form and provide ground for consideration of common mechanisms of pathogenesis. In this paper we report a case of a 27-year old Latina woman, a renal transplant recipient with systemic lupus erythematosus (SLE), who developed nephrotic range proteinuria 6 months after transplantation. The patient had recurrent acute renal failure and multiple biopsies were consistent with MCD. However, she lacked any other features of the typical nephrotic syndrome. An angiogram revealed a right external iliac vein stenosis in the region of renal vein anastomosis, which when restored resulted in normalization of creatinine and relief from proteinuria. We report a rare case of MCD developing secondary to iliac vein stenosis in a renal transplant recipient with SLE. Additionally we suggest that, in the event of biopsy-proven MCD presenting as an atypical nephrotic syndrome, alternative or secondary, potentially reversible, causes should be considered and explored. PMID- 26351599 TI - Isolated Hyperreligiosity in a Patient with Temporal Lobe Epilepsy. AB - A 40-year-old man with history of temporal lobe epilepsy presented to the emergency department with hyperreligiosity after medication noncompliance. After medications were resumed, he returned to baseline. Many famous prophets are believed to have suffered epilepsy. Waxman and Geschwind described a group of traits in patients with temporal lobe epilepsy consisting of hyperreligiosity, hypergraphia, altered sexual behavior, aggressiveness, preoccupation with details, and circumstantiality. The incidence of religious experiences ranges from 0.3 to 3.1 percent in patients with epilepsy. Religious experiences can be ictal, interictal, or postictal. Treatment is aimed at the underlying seizure etiology. PMID- 26351600 TI - Gabapentin-Induced Urinary Incontinence: A Rare Side Effect in Patients with Neuropathic Pain. AB - Gabapentin is a first-line agent for neuropathic pain management and has a favorable safety profile. The literature includes a few cases of gabapentin induced incontinence, and most of them involved patients with epilepsy who were between the ages of 12 and 43 years. Herein, we present three patients with neuropathic pain due to different diagnoses, and, to our knowledge, these are the oldest reported cases of urinary incontinence caused by gabapentin therapy. A 56 year-old female patient who underwent hip arthroplasty developed a sciatic nerve injury and neuropathic pain postoperatively. Ten days after she began taking gabapentin to relieve her pain, she experienced daily urinary incontinence. In another instance, a 63-year-old female patient was diagnosed with complex regional pain syndrome, and seven days after the initiation of gabapentin therapy, urinary incontinence developed. In addition, a 66-year-old male patient with neuropathic pain due to cervical disc pathology complained of urinary incontinence after the onset of gabapentin therapy. After discontinuing this drug, the incontinence symptoms resolved in these patients on the seventh, the first, and the second days, respectively. Physicians who administer gabapentin should inform their patients about the potential risk of gabapentin-induced incontinence and its negative impact on quality of life. PMID- 26351601 TI - Cerebral Amyloid Angiopathy-Related Inflammation: Report of a Case with Very Difficult Therapeutic Management. AB - Background. Cerebral amyloid angiopathy-related inflammation (CAA-ri) results from autoimmune response to beta-amyloid deposits in cerebral vessels. Its clinical course and complications have seldom been described in literature. Case Report. In a patient presenting with delirium and left hemiparesis the diagnosis of CAA-ri was supported by the finding of elevated anti-amyloid autoantibodies in the cerebrospinal fluid (CSF). Steroid therapy produced significant improvements in clinical and investigational assessments, but after two months, it caused Acute Respiratory Distress Syndrome. After steroid therapy discontinuation the patient presented a rapidly progressive dementia, Guillain-Barre syndrome, new cerebral ischemic lesions, and thrombosis of the right cephalic and subclavian veins that were treated with subcutaneous heparin. After a week the patient died because of brain hemorrhage. Conclusion. This case suggests caution in steroid therapy discontinuation and antithrombotic therapy administration in patients with CAA-ri. The CSF search of anti-amyloid autoantibodies could be helpful to support the diagnosis. PMID- 26351602 TI - Pheochromocytoma Presenting as Partial HELLP Syndrome. AB - Diagnosis of pheochromocytoma in partial HELLP syndrome is extremely rare. We report a case of a 25-year-old multigravida woman at 30 weeks of gestation who presented with clinical features consistent with partial HELLP syndrome. Her symptoms were not controlled by pharmacologic therapy, and the patient underwent urgent cesarean section. The patient gave birth to a viable baby, but she sustained an episode of ventricular fibrillation intraoperatively that did not result in any long-term sequelae. The patient's symptoms persisted postoperatively and work-up for secondary etiologies of hypertension demonstrated a right adrenal pheochromocytoma. Following resection, the patient's signs and symptoms resolved, and her lab tests normalized. PMID- 26351603 TI - Convergence Insufficiency/Divergence Insufficiency Convergence Excess/Divergence Excess: Some Facts and Fictions. AB - Great discrepancies are often encountered between the distance fixation and the near-fixation esodeviations and exodeviations. They are all attributed to either anomalies of the AC/A ratio or anomalies of the fusional convergence or divergence amplitudes. We report a case with pseudoconvergence insufficiency and another one with pseudoaccommodative convergence excess. In both cases, conv./div. excess and insufficiency were erroneously attributed to anomalies of the AC/A ratio or to anomalies of the fusional amplitudes. Our purpose is to show that numerous factors, other than anomalies in the AC/A ratio or anomalies in the fusional conv. or divergence amplitudes, can contaminate either the distance or the near deviations. This results in significant discrepancies between the distance and the near deviations despite a normal AC/A ratio and normal fusional amplitudes, leading to erroneous diagnoses and inappropriate treatment models. PMID- 26351604 TI - The Power of a Soccer Ball: A Traumatic Open Finger Dislocation-A Rare Case Presentation. AB - Proximal interphalangeal joint dislocations are injuries observed frequently and caused by axial loading on the finger in the extension. In this paper we present a traumatic open finger dislocation due to a ball hitting a wrestler. It was successfully treated with reduction and the volar plate and collateral bond fixation were applied with absorbable sutures. PMID- 26351605 TI - Immunophenotype Heterogeneity in Nasal Glomangiopericytoma. AB - Nasal glomangiopericytoma is rare. The immunophenotype is heterogeneous, more frequently smooth-muscle-actin and CD34-positive. We report expression patterns for several vascular-related proteins such as CD99, CD146, Bcl2, and WT1 as well as for treatment-related proteins such as mTOR and EGFR in a nasal glomangiopericytoma. The patient (woman, 86 years) presented with a left nasal tumefaction. The resected specimen (1.5-cm) showed a glomangiopericytoma. Tumor cells expressed smooth-muscle-actin, CD31, CD34, and progesterone receptor. They also expressed the vascular-cell-related proteins Bcl2, CD99, CD146, and WT1, as well as mTOR and EGFR. Nasal glomangiopericytomas show immunohistochemical heterogeneity for vascular-related markers, suggesting a possible extensive pericytic differentiation. The expression of potential targets for drug treatments such as mTOR and EGFR may impact on the clinical follow-up of these tumors occurring at advanced ages, which may require complex surgery. PMID- 26351606 TI - Does Papillary Carcinoma of Thyroglossal Duct Cyst Develop De Novo? AB - Backround. Thyroglossal duct cyst (TDC) is a developmental abnormality of the thyroid gland. Due to embryological remnants of thyroid tissue located in the TDC, the same malignant tumors that develop in the thyroid gland can also develop in the TDC. Methods. We present the unique case of a 39-year-old female with simultaneous de novo papillary carcinoma in a TDC and the thyroid gland. Results. With the suspicion of simultaneous papillary carcinoma in the TDC and the thyroid gland, Sistrunk procedure with total thyroidectomy and central neck exploration was performed. Conclusion. The clinician should have a high index of suspicion upon encountering papillary carcinoma of the TDC to differentiate de novo papillary carcinoma in the TDC from those originating from the thyroid gland, because papillary carcinoma in TDC may originate from an occult thyroid papillary carcinoma. PMID- 26351607 TI - Anaplastic Transformation of Papillary Thyroid Cancer in the Retroperitoneum. AB - Anaplastic thyroid carcinoma is an aggressive variant of thyroid cancer that in most cases arises from anaplastic transformation of terminally differentiated thyroid carcinomas. This process usually occurs in the thyroid or cervical lymph nodes. Anaplastic transformation in distant metastatic sites is exceedingly rare, only previously documented in a few case reports. We report a rare case of anaplastic transformation of papillary thyroid carcinoma within a large retroperitoneal metastasis in a 64-year-old male 30 years after the initial diagnosis. PMID- 26351609 TI - Inguinal Hernia Containing Uterus, Fallopian Tube, and Ovary in a Premature Newborn. AB - A female infant weighing 2,200 g was delivered at 34 weeks of gestation by vaginal delivery. She presented with an irreducible mass in the left inguinal region at 32 days of age. An ultrasonography (US) was performed and an incarcerated hernia containing uterus, fallopian tube, and ovary was diagnosed preoperatively. Surgery was performed through an inguinal approach; the uterus, fallopian tube, and ovary were found in the hernia sac. High ligation and an additional repair of the internal inguinal ring were performed. Patent processus vaginalis was found during contralateral exploration and also closed. The postoperative course was uneventful. After one year of follow-up, there have been no signs of recurrence. PMID- 26351608 TI - Metachronous Bilateral Testicular Leydig-Like Tumors Leading to the Diagnosis of Congenital Adrenal Hyperplasia (Adrenogenital Syndrome). AB - A 33-year-old male with a history of left testis Leydig cell tumor (LCT), 3-month status after left radical orchiectomy, presented with a rapidly enlarging (0.6 cm to 3.7 cm) right testicular mass. He underwent a right radical orchiectomy, sections interpreted as showing a similar Leydig cell-like oncocytic proliferation, with a differential diagnosis including metachronous bilateral LCT and metachronous bilateral testicular tumors associated with congenital adrenal hyperplasia (a.k.a. "testicular adrenal rest tumors" (TARTs) and "testicular tumors of the adrenogenital syndrome" (TTAGS)). Additional workup demonstrated a markedly elevated serum adrenocorticotropic hormone (ACTH) and elevated adrenal precursor steroid levels. He was diagnosed with congenital adrenal hyperplasia, 3beta-hydroxysteroid dehydrogenase deficiency (3BHSD) type, and started on treatment. Metachronous bilateral testicular masses in adults should prompt consideration of adult presentation of CAH. Since all untreated CAH patients are expected to have elevated serum ACTH, formal exclusion of CAH prior to surgical resection of a testicular Leydig-like proliferation could be accomplished by screening for elevated serum ACTH. PMID- 26351610 TI - Chronic Thoracic Aortic Aneurysm Presenting 29 Years following Trauma. AB - Blunt, nonpenetrating injuries of the thoracic aorta are uncommon and associated with a high mortality rate within the first hour. Aortic injury is missed in 1-2% of patients that survive to hospital, and a chronic thoracic aortic aneurysm may subsequently form. We present a case in which a chronic thoracic aortic aneurysm was diagnosed 29 years following a significant motor vehicle accident. We discuss the epidemiology, presentation, and management of this uncommon consequence of blunt, nonpenetrating aortic injury. Our case illustrates an important clinical lesson; a past medical history of trauma should not be overlooked at any patient assessment. PMID- 26351611 TI - Acute Respiratory Distress Syndrome after Treatment of Metastatic Prostate Cancer with Taxotere: A Case Report and Literature Review. AB - Prostate cancer is the most common cancer in men. Docetaxel is a common chemotherapeutic agent that has proven its efficacy in the treatment of patients with both castration sensitive and resistant metastatic prostate cancer. We report a case of acute respiratory distress syndrome (ARDS) in a patient with metastatic prostate cancer treated with docetaxel (Taxotere). ARDS is very rare but life threatening complication of docetaxel which requires aggressive supportive care and close monitoring. Better awareness and prompt diagnosis of this treatment related ARDS will improve the effectiveness and outcome of its management. PMID- 26351612 TI - Mixed Germ Cell Tumor of Testis with Isolated Scapular Metastasis: A Case Report and Review of the Literature. AB - Bone metastasis is a rare entity in germ cell tumor of testis and is a poor prognostic site. It is usually associated with synchronous metastasis at other sites. Till now very few cases of isolated bone metastasis of germ cell tumor of testis have been reported but none have reported scapular metastasis. We are reporting a case of nonseminomatous germ cell tumor of right testis that was operated eight months ago and now presented with isolated scapular metastasis. Histopathology of the scapular tissue revealed rhabdomyosarcoma or poorly differentiated synovial sarcoma. Immunohistochemistry with serum markers concluded it to be metastatic germ cell tumor. To the best of our knowledge this is the first reported case of scapular metastasis of testicular germ cell tumor. This case is being reported here due to dilemmatic way of presentation and also to emphasize that histopathology may sometimes misguide and immunohistochemistry is necessary in such cases. PMID- 26351613 TI - Clinicoetiological Characterization of Infectious Vaginitis amongst Women of Reproductive Age Group from Navi Mumbai, India. AB - Vaginitis is one of the commonest reproductive tract infections in sexually active women. In the present study clinicoetiological characterization of infectious vaginitis amongst 380 women of reproductive age group (18-45 years) was done. Bacterial vaginosis (BV) was detected by Nugent's scoring, Candida infection by culture, and trichomoniasis (TV) by wet mount. One hundred and ten (28.9%) women presented with symptoms of vaginitis. The presenting symptoms were vaginal discharge 106 (96.4%), vulval itching/irritation 19 (17.3%), malodor 5 (4.5%), pain in abdomen 3 (2.7%), and dysuria 1 (0.9%). The commonest etiology detected was Candida in 33 (30%) cases, of which 18 (54.5%) were C. albicans and 15 (45.5%) non-albicans Candida (NAC) infections. The NAC isolates were C. glabrata (n = 10), C. tropicalis (n = 3), and C. krusei (n = 2). BV and TV were observed in 19 (17.3%) and 2 (1.8%) cases, respectively. A statistically significant association between Candida infection and presence of curdy-white discharge (p = 0.001) and vulval itching/irritation (p = 0.007) was noted. To conclude, we observed the etiological predominance of Candida infection, with considerable prevalence of NAC, indicating the need for microbiological investigation up to species level in cases of Candida infections, to ensure appropriate management. PMID- 26351614 TI - Vitamin D and Alzheimer's Disease: Neurocognition to Therapeutics. AB - Alzheimer's disease (AD), the major cause of dementia worldwide, is characterized by progressive loss of memory and cognition. The sporadic form of AD accounts for nearly 90% of the patients developing this disease. The last century has witnessed significant research to identify various mechanisms and risk factors contributing to the complex etiopathogenesis of AD by analyzing postmortem AD brains and experimenting with animal and cell culture based models. However, the treatment strategies, as of now, are only symptomatic. Accumulating evidences suggested a significant association between vitamin D deficiency, dementia, and AD. This review encompasses the beneficial role of vitamin D in neurocognition and optimal brain health along with epidemiological evidence of the high prevalence of hypovitaminosis D among aged and AD population. Moreover, disrupted signaling, altered utilization of vitamin D, and polymorphisms of several related genes including vitamin D receptor (VDR) also predispose to AD or AD-like neurodegeneration. This review explores the relationship between this gene environmental influence and long term vitamin D deficiency as a risk factor for development of sporadic AD along with the role and rationale of therapeutic trials with vitamin D. It is, therefore, urgently warranted to further establish the role of this potentially neuroprotective vitamin in preventing and halting progressive neurodegeneration in AD patients. PMID- 26351615 TI - Relationship between Postural Deformities and Frontal Function in Parkinson's Disease. AB - Postural deformities and executive dysfunction (ED) are common symptoms of Parkinson's disease (PD); however, the relationship between postural deformities and ED in patients with PD remains unclear. This study assessed the relationship between postural deformities and ED in patients with PD. Sixty-five patients with sporadic PD were assessed for the severity of postural deformities and executive function. The severity of postural deformities was scored using the United Parkinson's Disease Rating Scale item 28 score: no postural deformity (0), mild postural deformities (1), or severe postural deformities (2-4). Executive function was assessed using the Behavioral Assessment of the Dysexecutive Syndrome (BADS) and an age-controlled standardized BADS score <70 was defined as ED. Age-controlled standardized BADS scores were compared across the three groups using the Kruskal-Wallis test. Relationship between ED and the severity of postural deformities was assessed using the Mann-Whitney U test. Age-controlled standardized BADS score significantly differed among the three groups (P = 0.005). ED was significantly related to the severity of postural deformities (P = 0.0005). The severity of postural deformities was associated with a lower age controlled standardized BADS score and ED, and these findings suggest that postural deformities were associated with frontal dysfunction in patients with PD. PMID- 26351616 TI - Addenbrooke's Cognitive Examination and Individual Domain Cut-Off Scores for Discriminating between Different Cognitive Subtypes of Parkinson's Disease. AB - Objective. The main aim of this study was to verify the sensitivity and specificity of Addenbrooke's Cognitive Examination-Revised (ACE-R) in discriminating between Parkinson's disease (PD) with normal cognition (PD-NC) and PD with mild cognitive impairment (PD-MCI) and between PD-MCI and PD with dementia (PD-D). We also evaluated how ACE-R correlates with neuropsychological cognitive tests in PD. Methods. We examined three age-matched groups of PD patients diagnosed according to the Movement Disorder Society Task Force criteria: PD-NC, PD-MCI, and PD-D. ROC analysis was used to establish specific cut-off scores of ACE-R and its domains. Correlation analyses were performed between ACE-R and its subtests with relevant neuropsychological tests. Results. Statistically significant differences between groups were demonstrated in global ACE-R scores and subscores, except in the language domain. ACE-R cut-off score of 88.5 points discriminated best between PD-MCI and PD-NC (sensitivity 0.68, specificity 0.91); ACE-R of 82.5 points distinguished best between PD-MCI and PD D (sensitivity 0.70, specificity 0.73). The verbal fluency domain of ACE-R demonstrated the best discrimination between PD-NC and PD-MCI (cut-off score 11.5; sensitivity 0.70, specificity 0.73) while the orientation/attention subscore was best between PD-MCI and PD-D (cut-off score 15.5; sensitivity 0.90, specificity 0.97). ACE-R scores except for ACE-R language correlated with specific cognitive tests of interest. PMID- 26351617 TI - Interleukin-6 May Contribute to Mortality in Parkinson's Disease Patients: A 4 Year Prospective Study. AB - Objectives. The association between abnormal serum immunomarkers and mortality in 53 consecutive Parkinson's disease patients was studied. Materials and Methods. The plasma level of specific inflammatory cytokines was investigated: mannan binding lectin (MBL), interleukin- (IL-) 6, and tumor necrosis factor-alpha (TNF alpha). The baseline serum immunomarkers obtained from patients who died (n = 16) during a four-year follow-up period were compared with the data of patients who survived (n = 37). Results. The baseline level of IL-6 was significantly higher in the deceased patients than in the survivors. Elevated IL-6 levels and age were major independent contributors to disease mortality. Differences between other plasma cytokine level abnormalities were not significant. Conclusion. This study showed that IL-6 elevation may be a marker of increased mortality risk in Parkinson's disease patients. The inflammation may act in association with other factors and comorbidities in progressive neurodegenerative pathology. PMID- 26351618 TI - Regarding Disclosure of Psychological Testing Information. PMID- 26351619 TI - Efficacy of Transcranial Magnetic Stimulation (TMS) in the Treatment of Schizophrenia: A Review of the Literature to Date. AB - We reviewed the literature on transcranial magnetic stimulation and its uses and efficacy in schizophrenia. Multiple sources were examined on transcranial magnetic stimulation efficacy in relieving positive and negative symptoms of schizophrenia. Literature review was conducted via Ovid Medline and PubMed databases. We found multiple published studies and metaanalyses that give evidence that repetitive transcranial magnetic stimulation can have benefit in relieving positive and negative symptoms of schizophrenia, particularly auditory hallucinations. These findings should encourage the psychiatric community to expand research into other applications for which transcranial magnetic stimulation may be used to treat patients with psychiatric disability. PMID- 26351620 TI - Evaluation of the Psychometric Properties of the Cognitive Distortions Questionnaire (CD-Quest) in a Sample of Undergraduate Students. AB - OBJECTIVE: The aim of the study was to assess the initial psychometric properties of the Cognitive Distortions Questionnaire (CD-Quest) in its Brazilian Portuguese version tested in adult undergraduate students. METHODS: Brazilian undergraduate medical and psychology students comprising the sample (n=184) completed the following measures: Cognitive Distortions Questionnaire, Beck Depression Inventory and Beck Anxiety Inventory. These self-report instruments were administered collectively in classrooms. RESULTS: The Cognitive Distortions Questionnaire showed adequate internal consistency (Cronbach's alpha=0.85) and concurrent validity with Beck Depression Inventory (r=0.65, p<0.001) and Beck Anxiety Inventory (r=0.52, p<0.001). Furthermore, it was able to discriminate between groups possessing depressive (Beck Depression Inventory composite score >=12) and anxious (Beck Anxiety Inventory composite score >= 11) indicators from those not possessing them (p<0.001). Principal components showed the measure was unidimensional, and it explained about 29 percent of the data variance. A confirmatory factor analysis showed that all the regression coefficients are greater than or equal to 0.40 CONCLUSION: The original Brazilian version of the Cognitive Distortions Questionnaire is adequate for use in the context of national undergraduate students and is able to separate different cognitive distortions. However, further studies using clinical samples are needed. PMID- 26351621 TI - Electroconvulsive Therapy in Multiple Sclerosis. AB - We performed a literature search regarding the safety and efficacy of electroconvulsive therapy in patients with multiple sclerosis and comorbid psychiatric symptoms. Literature review was conducted via PubMed databases. Of the cases we reviewed, most subjects with multiple sclerosis reported significant psychiatric symptom relief, with only a handful reporting neurologic deterioration. There was some evidence that active white matter lesions may be predictive of neurologic deterioration when electroconvulsive therapy is used in patients with multiple sclerosis. A brief description of the pathophysiology and effects of depression in patients with multiple sclerosis is also provided. Although no clinical recommendations or meaningful conclusions can be drawn without further investigation, the literature suggests that electroconvulsive therapy for treatment of psychiatric illnesses in patients with multiple sclerosis is safe and efficacious. PMID- 26351622 TI - Auditory Neuropathy Spectrum Disorder Masquerading as Social Anxiety. AB - The authors report a case of a 47-year-old man who presented with treatment resistant anxiety disorder. Behavioral observation raised clinical suspicion of auditory neuropathy spectrum disorder. The presence of auditory neuropathy spectrum disorder was confirmed on audiological investigations. The patient was experiencing extreme symptoms of anxiety, which initially masked the underlying diagnosis of auditory neuropathy spectrum disorder. Challenges in diagnosis and treatment of auditory neuropathy spectrum disorder are discussed. PMID- 26351623 TI - EHR DOCUMENTATION: How to Keep Your Patients Safe, Keep Your Hard-Earned Money, and Stay Out of Court. PMID- 26351624 TI - BORDERLINE PERSONALITY DISORDER IN THE MEDICAL SETTING: Suggestive Behaviors, Syndromes, and Diagnoses. AB - Borderline personality disorder is a personality dysfunction that is characterized by disinhibition and impulsivity, which oftentimes manifest as self regulation difficulties. Patients with this disorder have always been present in medical settings, but have been described as "difficult patients" rather than patients with borderline personality disorder. According to empirical findings, a number of behaviors and medical syndromes/diagnoses are suggestive of borderline personality disorder. Suggestive behaviors in the medical setting may include aggressive or disruptive behaviors, the intentional sabotage of medical care, and excessive healthcare utilization. Suggestive medical syndromes and diagnoses in the medical setting may include alcohol and substance misuse (including the abuse of prescription medications), multiple somatic complaints, chronic pain, obesity, sexual impulsivity, and hair pulling. While not all-inclusive or diagnostic, these behaviors and syndromes/diagnoses may invite further clinical evaluation of the patient for borderline personality disorder. PMID- 26351625 TI - Quercetin reduces Ehrlich tumor-induced cancer pain in mice. AB - Cancer pain directly affects the patient's quality of life. We have previously demonstrated that the subcutaneous administration of the mammary adenocarcinoma known as Ehrlich tumor induces pain in mice. Several studies have shown that the flavonoid quercetin presents important biological effects, including anti inflammatory, antioxidant, analgesic, and antitumor activity. Therefore, the analgesic effect and mechanisms of quercetin were evaluated in Ehrlich tumor induced cancer pain in mice. Intraperitoneal (i.p.) treatments with quercetin reduced Ehrlich tumor-induced mechanical and thermal hyperalgesia, but not paw thickness or histological alterations, indicating an analgesic effect without affecting tumor growth. Regarding the analgesic mechanisms of quercetin, it inhibited the production of hyperalgesic cytokines IL-1beta and TNFalpha and decreased neutrophil recruitment (myeloperoxidase activity) and oxidative stress. Naloxone (opioid receptor antagonist) inhibited quercetin analgesia without interfering with neutrophil recruitment, cytokine production, and oxidative stress. Importantly, cotreatment with morphine and quercetin at doses that were ineffective as single treatment reduced the nociceptive responses. Concluding, quercetin reduces the Ehrlich tumor-induced cancer pain by reducing the production of hyperalgesic cytokines, neutrophil recruitment, and oxidative stress as well as by activating an opioid-dependent analgesic pathway and potentiation of morphine analgesia. Thus, quercetin treatment seems a suitable therapeutic approach for cancer pain that merits further investigation. PMID- 26351626 TI - Ex vivo nicotine stimulation augments the efficacy of human peripheral blood mononuclear cell-derived dendritic cell vaccination via activating Akt-S6 pathway. AB - Our previous studies showed that alpha7 nicotinic acetylcholine receptor (nAchR) agonist nicotine has stimulatory effects on murine bone marrow-derived semimature DCs, but the effect of nicotine on peripheral blood mononuclear cell- (PBMC-) derived human semimature dendritic cells (hu-imDCs) is still to be clarified. In the present study, hu-imDCs (cultured 4 days) were conferred with ex vivo lower dose nicotine stimulation and the effect of nicotine on surface molecules expression, the ability of cross-presentation, DCs-mediated PBMC priming, and activated signaling pathways were determined. We could demonstrate that the treatment with nicotine resulted in increased surface molecules expression, enhanced hu-imDCs-mediated PBMC proliferation, upregulated release of IL-12 in the supernatant of cocultured DCs-PBMC, and augmented phosphorylation of Akt and ribosomal protein S6. Nicotine associated with traces of LPS efficiently enhanced endosomal translocation of internalized ovalbumin (OVA) and increased TAP-OVA colocalization. Importantly, the upregulation of nicotine-increased surface molecules upregulation was significantly abrogated by the inhibition of Akt kinase. These findings demonstrate that ex vivo nicotine stimulation augments hu imDCs surface molecules expression via Akt-S6 pathway, combined with increased Ag presentation result in augmented efficacy of DCs-mediated PBMC proliferation and Th1 polarization. PMID- 26351627 TI - Characteristics of Intravascular Large B-Cell Lymphoma Limited to the Glomerular Capillaries: A Case Report. AB - A 65-year-old woman was admitted to our hospital for the evaluation of rapidly progressive renal dysfunction with serum creatinine of 2.7 mg/dl and urinary protein of 1.5 g daily. C-reactive protein (CRP) was 0.1 mg/dl. Kidney-limited intravascular large B-cell lymphoma (IVL) localized to the glomerular capillaries was diagnosed because the intraglomerular cells were positive for CD20 and CD79a, while there was no positivity in the extraglomerular kidney and extrarenal organs. Treatment with rituximab, cyclophosphamide, hydroxydaunomycin, vincristine, and prednisolone was started, and the patient has since been doing well. When IVL is limited to the intraglomerular capillaries, CRP may not be elevated. PMID- 26351628 TI - Isolation, Expression, and Promoter Analysis of GbWRKY2: A Novel Transcription Factor Gene from Ginkgo biloba. AB - WRKY transcription factor is involved in multiple life activities including plant growth and development as well as biotic and abiotic responses. We identified 28 WRKY genes from transcriptome data of Ginkgo biloba according to conserved WRKY domains and zinc finger structure and selected three WRKY genes, which are GbWRKY2, GbWRKY16, and GbWRKY21, for expression pattern analysis. GbWRKY2 was preferentially expressed in flowers and strongly induced by methyl jasmonate. Here, we cloned the full-length cDNA and genomic DNA of GbWRKY2. The full-length cDNA of GbWRKY2 was 1,713 bp containing a 1,014 bp open reading frame encoding a polypeptide of 337 amino acids. The GbWRKY2 genomic DNA had one intron and two exons. The deduced GbWRKY2 contained one WRKY domain and one zinc finger motif. GbWRKY2 was classified into Group II WRKYs. Southern blot analysis revealed that GbWRKY2 was a single copy gene in G. biloba. Many cis-acting elements related to hormone and stress responses were identified in the 1,363 bp-length 5'-flanking sequence of GbWRKY2, including W-box, ABRE-motif, MYBCOREs, and PYRIMIDINE-boxes, revealing the molecular mechanism of upregulated expression of GbWRKY2 by hormone and stress treatments. Further functional characterizations in transiently transformed tobacco leaves allowed us to identify the region that can be considered as the minimal promoter. PMID- 26351630 TI - Synthesis and Properties of pH-, Thermo-, and Salt-Sensitive Modified Poly(aspartic acid)/Poly(vinyl alcohol) IPN Hydrogel and Its Drug Controlled Release. AB - Modified poly(aspartic acid)/poly(vinyl alcohol) interpenetrating polymer network (KPAsp/PVA IPN) hydrogel for drug controlled release was synthesized by a simple one-step method in aqueous system using poly(aspartic acid) grafting 3 aminopropyltriethoxysilane (KH-550) and poly(vinyl alcohol) (PVA) as materials. The hydrogel surface morphology and composition were characterized by Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The thermal stability was analyzed by thermogravimetric analysis (TGA). The swelling properties and pH, temperature, and salt sensitivities of KPAsp, KPAsp/PVA semi-interpenetrating polymer network (semi-IPN), and KPAsp/PVA IPN hydrogels were also investigated. All of the three hydrogels showed ampholytic pH responsive properties, and swelling behavior was also extremely sensitive to the temperature, ionic strength, and cationic species. Finally, the drug controlled release properties of the three hydrogels were evaluated and results indicated that three hydrogels could control drug release by external surroundings stimuli. The drug controlled release properties of KPAsp/PVA IPN hydrogel are the most outstanding, and the correlative measured release profiles of salicylic acid at 37 degrees C were 32.6 wt% at pH = 1.2 (simulated gastric fluid) and 62.5 wt% at pH = 7.4 (simulated intestinal fluid), respectively. These results indicated that KPAsp/PVA IPN hydrogels are a promising carrier system for controlled drug delivery. PMID- 26351629 TI - Influence of Orthodontic Rapid Maxillary Expansion on Nocturnal Enuresis in Children. AB - BACKGROUND: The etiology of nocturnal enuresis (NE) is multifactorial and has not been fully explained yet. New ways of treatment are constantly being investigated, including the rapid maxillary expansion (RME). METHODS: A total of 41 patients diagnosed with NE were divided into two experimental groups: A and B. Group A included 16 children who have been treated with RME. Group B comprised 25 children who have not undertaken orthodontic treatment. Children from both groups have been monitored in monthly intervals, during a 12-month period, towards the intensification of NE. The comparative analysis of both groups has been conducted after 3 years of observation. RESULTS: Statistical analysis has shown a 4.5 times increase of the probability of reduction of NE in the case of the treated group in comparison with the group of children who have not undergone orthodontic treatment. Unfortunately, the chance of obtaining total dryness diminished proportionally to the higher degree of intensification of enuresis at the beginning of the test. CONCLUSION: RME can constitute an alternative method of NE treatment in children, irrespective of the occurrence of upper jaw narrowing. PMID- 26351631 TI - Qat Chewing and Periodontal Pathogens in Health and Disease: Further Evidence for a Prebiotic-Like Effect. AB - AIM: Qat chewing has been reported to induce subgingival microbial shifts suggestive of prebiotic-like properties. The objective here was to assess the effect of qat chewing on a panel of classical and new putative periopathogens in health and periodontitis. MATERIALS AND METHODS: 40 qat chewers and 40 nonchewers, equally stratified by periodontal health status, were recruited. Taqman, real-time PCR was used to quantify total bacteria, Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Parvimonas micra, Filifactor alocis, Synergistetes, and TM7s in pooled subgingival biofilm samples. Differences in microbial parameters between the study groups were analysed using ordinal regression. RESULTS: In health, the qat chewers harboured significantly lower relative counts of P. gingivalis, T. forsythia, Synergistetes, and TM7s after adjustment for multiple comparisons (P <= 0.007). At nominal significance level, they also carried lower counts of TM7s and P. micra (P <= 0.05). In periodontitis, the chewers had lower counts of all taxa; however, only T. denticola withstood correction for multiple comparisons (P <= 0.0063). CONCLUSIONS: Qat chewing is associated with lower proportions of periopathogens, particularly in subjects with healthy periodontium, which supports previous reports of its prebiotic-like properties. This potentially beneficial biological effect can be exploited by attempting to isolate the active fraction. PMID- 26351632 TI - The Effect of Young Age in Hormone Receptor Positive Breast Cancer. AB - BACKGROUND: Studies have shown that young breast cancer patients have more advanced disease and worse survival compared to older patients. Our objective was to study disease characteristics and survival in the subset of young women with hormone receptor positive (HR+) and HER2 negative (HER2-) cancer. METHODS: We retrospectively analyzed HR+/HER2- breast cancer patients who underwent surgery at our institution between 2002 and 2010. We compared clinical characteristics, pathology, treatment, and recurrence-free survival between younger (<=40 years) and older (>40 years) patients. RESULTS: Of 669 HR+/HER2- breast cancer cases, 54 (8.1%) patients were 40 years or younger. Younger patients had more luminal B subtype, high grade, poor differentiation, and increased lymphovascular invasion. Younger women were treated more often with mastectomy and adjuvant chemotherapy. Although the unadjusted recurrence-free survival at median 55-month follow-up was lower in younger women, adjusting for stage, there was no significant difference (90.7% versus 89.3%, p = 0.74) between groups. CONCLUSION: Younger patients with HR+/HER2- breast cancer had more advanced disease and more aggressive treatment than older patients. The unfavorable pathologic features suggest a biologically different tumor in young women. After adjusting for these factors, younger patients have a recurrence-free survival similar to older patients. PMID- 26351633 TI - Drug Susceptibility Testing of 31 Antimicrobial Agents on Rapidly Growing Mycobacteria Isolates from China. AB - OBJECTIVES: Several species of rapidly growing mycobacteria (RGM) are now recognized as human pathogens. However, limited data on effective drug treatments against these organisms exists. Here, we describe the species distribution and drug susceptibility profiles of RGM clinical isolates collected from four southern Chinese provinces from January 2005 to December 2012. METHODS: Clinical isolates (73) were subjected to in vitro testing with 31 antimicrobial agents using the cation-adjusted Mueller-Hinton broth microdilution method. The isolates included 55 M. abscessus, 11 M. fortuitum, 3 M. chelonae, 2 M. neoaurum, and 2 M. septicum isolates. RESULTS: M. abscessus (75.34%) and M. fortuitum (15.07%), the most common species, exhibited greater antibiotic resistance than the other three species. The isolates had low resistance to amikacin, linezolid, and tigecycline, and high resistance to first-line antituberculous agents, amoxicillin-clavulanic acid, rifapentine, dapsone, thioacetazone, and pasiniazid. M. abscessus and M. fortuitum were highly resistant to ofloxacin and rifabutin, respectively. The isolates showed moderate resistance to the other antimicrobial agents. CONCLUSIONS: Our results suggest that tigecycline, linezolid, clofazimine, and cefmetazole are appropriate choices for M. abscessus infections. Capreomycin, sulfamethoxazole, tigecycline, clofazimine, and cefmetazole are potentially good choices for M. fortuitum infections. Our drug susceptibility data should be useful to clinicians. PMID- 26351634 TI - Towards a Next-Generation Sequencing Diagnostic Service for Tumour Genotyping: A Comparison of Panels and Platforms. AB - Detection of clinically actionable mutations in diagnostic tumour specimens aids in the selection of targeted therapeutics. With an ever increasing number of clinically significant mutations identified, tumour genetic diagnostics is moving from single to multigene analysis. As it is still not feasible for routine diagnostic laboratories to perform sequencing of the entire cancer genome, our approach was to undertake targeted mutation detection. To optimise our diagnostic workflow, we evaluated three target enrichment strategies using two next generation sequencing (NGS) platforms (Illumina MiSeq and Ion PGM). The target enrichment strategies were Fluidigm Access Array custom amplicon panel including 13 genes (MiSeq sequencing), the Oxford Gene Technologies (OGT) SureSeq Solid Tumour hybridisation panel including 60 genes (MiSeq sequencing), and an Ion AmpliSeq Cancer Hotspot Panel including 50 genes (Ion PGM sequencing). DNA extracted from formalin-fixed paraffin-embedded (FFPE) blocks of eight previously characterised cancer cell lines was tested using the three panels. Matching genomic DNA from fresh cultures of these cell lines was also tested using the custom Fluidigm panel and the OGT SureSeq Solid Tumour panel. Each panel allowed mutation detection of core cancer genes including KRAS, BRAF, and EGFR. Our results indicate that the panels enable accurate variant detection despite sequencing from FFPE DNA. PMID- 26351635 TI - Sublingual Immunotherapy with a Five-Grass Pollen Tablet in Adult Patients with Allergic Rhinitis: An Open, Prospective, Noninterventional, Multicenter Study. AB - BACKGROUND: Although the safety and efficacy of sublingual immunotherapy (SLIT) with a five-grass pollen tablet have been demonstrated in randomized clinical trials (RCTs), these outcomes must always be evaluated in real-life medical practice. METHODS: In a prospective, open-label, noninterventional, "real-life" study in Germany, we evaluated the safety, tolerability, and effectiveness of SLIT with a five-grass pollen tablet in adults with grass-pollen-induced allergic rhinoconjunctivitis. RESULTS: 808 adults were enrolled between September 2008 and December 2009. 35.3% of the participants experienced at least one adverse drug reaction (ADR), the most common of which were mild-to-moderate gastrointestinal and respiratory disorders. Serious ADRs considered causally related to SLIT treatment occurred in four patients. Overall, the five-grass pollen tablet was considered to have good or very good tolerability by most investigators and patients. Treatment was associated with the relief of nasal, ocular, and bronchial symptoms and decreased symptomatic medication use. However, interpretation of clinical improvements was limited by lower atmospheric grass pollen levels during the study season (relative to the preceding season). CONCLUSIONS: In a large population of patients treated in real-life medical practice, SLIT with a five-grass pollen tablet was safe and well tolerated. The patient-reported symptom relief suggests that SLIT was associated with clinical benefits. PMID- 26351636 TI - Isolation, Culture, and Characterization of Chicken Cartilage Stem/Progenitor Cells. AB - A chondrocyte progenitor population isolated from the surface zone of articular cartilage has become a promising cell source for cell-based cartilage repair. The cartilage-derived stem/progenitor cells are multipotent stem cells, which can differentiate into three cell types in vitro including adipocytes, osteoblasts, and chondrocytes. Much work has been done on cartilage stem/progenitor cells (CSPCs) from people, horses, and cattle, but the relatively little literature has been published about these cells in chickens. In our work, CSPCs were isolated from chicken embryos in incubated eggs for 20 days. In order to inquire into the biological characteristics of chicken CSPCs, immunofluorescence, reverse transcription-polymerase chain reaction (RT-PCR), and flow cytometry were adopted to detect the characteristic surface markers of CSPCs. Primary CSPCs were subcultured to passage 22 and, for purpose of knowing the change of cell numbers, we drew the growth curves. Isolated CSPCs were induced to adipocytes, osteoblasts, and chondrocytes. Our results suggest that we have identified and characterised a novel cartilage progenitor population resident in chicken articular cartilage and CSPCs isolated from chickens possess similar biological characteristics to those from other species, which will greatly benefit future cell-based cartilage repair therapies. PMID- 26351637 TI - Expression of the Genes Encoding the Trk and Kdp Potassium Transport Systems of Mycobacterium tuberculosis during Growth In Vitro. AB - Two potassium (K(+))-uptake systems, Trk and Kdp, are operative in Mycobacterium tuberculosis (Mtb), but the environmental factors triggering their expression have not been determined. The current study has evaluated the expression of these genes in the Mtb wild-type and a trk-gene knockout strain at various stages of logarithmic growth in relation to extracellular K(+) concentrations and pH. In both strains, mRNA levels of the K(+)-uptake encoding genes were relatively low compared to those of the housekeeping gene, sigA, at the early- and mid-log phases, increasing during late-log. Increased gene expression coincided with decreased K(+) uptake in the context of a drop in extracellular pH and sustained high extracellular K(+) concentrations. In an additional series of experiments, the pH of the growth medium was manipulated by the addition of 1N HCl/NaOH. Decreasing the pH resulted in reductions in both membrane potential and K(+) uptake in the setting of significant induction of genes encoding both K(+) transporters. These observations are consistent with induction of the genes encoding the active K(+) transporters of Mtb as a strategy to compensate for loss of membrane potential-driven uptake of K(+) at low extracellular pH. Induction of these genes may promote survival in the acidic environments of the intracellular vacuole and granuloma. PMID- 26351638 TI - Hearing Assessment after Treatment of Nasopharyngeal Carcinoma with CRT and IMRT Techniques. AB - OBJECTIVES: This study analyzed the long-term hearing loss after treatment of primary nasopharyngeal carcinoma to elucidate its causal factors. METHODS: Ninety two nasopharyngeal carcinoma patients were treated with radiotherapy or chemoradiotherapy. Pure tone audiometry was performed before the therapy and annually up to 9 years after completing treatment. The hearing thresholds were corrected for age-related deterioration and compared to the results without adjusting for age. RESULTS: The mean air and bone conduction threshold with and without correction for age-related deterioration differed significantly 2-9 years after completing radiotherapy (p < 0.05). The audiometry results with age correction showed a flattened configuration compared to the results without age correction. The total radiation dose and radiation modality showed a causal relationship with a greater incidence of hearing loss after therapy (p < 0.05). There was more deterioration in the air and bone hearing thresholds with conformal radiotherapy than intensity-modulated radiotherapy (p < 0.001). A radiation dose >72 cGy resulted in more severe hearing loss than <72 cGy (p < 0.05). CONCLUSION: Hearing loss after completing therapy should be corrected for age-related hearing deterioration to reveal the true extent to which the loss is a therapeutic complication. Both the radiation modality used and the dose were significantly associated with hearing loss. PMID- 26351639 TI - Prognostic Implications of Serum Lipid Metabolism over Time during Sepsis. AB - BACKGROUND: Despite extensive research and an improved standard of care, sepsis remains a disorder with a high mortality rate. Sepsis is accompanied by severe metabolic alterations. METHODS: We evaluated 117 patients with sepsis (severe sepsis [n = 19] and septic shock [n = 98]) who were admitted to the intensive care unit. Serum cholesterol, triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), free fatty acid (FFA), and apolipoprotein (Apo) A I levels were measured on days 0, 1, 3, and 7. RESULTS: Nonsurvivors had low levels of cholesterol, TG, HDL, LDL, and Apo A-I on days 0, 1, 3, and 7. In a linear mixed model analysis, the variations in TG, LDL, FFA, and Apo A-I levels over time differed significantly between the groups (p = 0.043, p = 0.020, p = 0.005, and p = 0.015, resp.). According to multivariate analysis, TG levels and SOFA scores were associated with mortality on days 0 and 1 (p = 0.018 and p = 0.008, resp.). CONCLUSIONS: Our study illustrated that TG levels are associated with mortality in patients with sepsis. This may be attributable to alterations in serum lipid metabolism during sepsis, thus modulating the host response to inflammation in critically ill patients. PMID- 26351640 TI - Basic Fibroblast Growth Factor Ameliorates Endothelial Dysfunction in Radiation Induced Bladder Injury. AB - This study was designed to explore the effect of basic fibroblast growth factor (bFGF) on radiation-induced endothelial dysfunction and histological changes in the urinary bladder. bFGF was administrated to human umbilical vein cells (HUVEC) or urinary bladder immediately after radiation. Reduced expression of thrombomodulin (TM) was indicated in the HUVEC and urinary bladder after treatment with radiation. Decreased apoptosis was observed in HUVEC treated with bFGF. Administration of bFGF increased the expression of TM in HUVEC medium, as well as in the urinary bladder at the early and delayed phases of radiation induced bladder injury (RIBI). At the early phase, injection of bFGF increased the thickness of urothelium and reduced inflammation within the urinary bladder. At the delayed phase, bFGF was effective in reducing fibrosis within the urinary bladder. Our results indicate that endothelial dysfunction is a prominent feature of RIBI. Administration of bFGF can ameliorate radiation-induced endothelial dysfunction in urinary bladder and preserve bladder histology at early and delayed phases of RIBI. PMID- 26351641 TI - Corrigendum to "Evacuation after the Fukushima Daiichi Nuclear Power Plant Accident is a Cause of Diabetes: Results from the Fukushima Health Management Survey". PMID- 26351642 TI - Effects of E2HSA, a Long-Acting Glucagon Like Peptide-1 Receptor Agonist, on Glycemic Control and Beta Cell Function in Spontaneous Diabetic db/db Mice. AB - Glucagon like peptide-1 (GLP-1) receptor agonists such as exendin-4 have been widely used but their short half-life limits their therapeutic value. The recombinant protein, E2HSA, is a novel, long-acting GLP-1 receptor agonist generated by the fusion of exendin-4 with human serum albumin. In mouse pancreatic NIT-1 cells, E2HSA activated GLP-1 receptor with similar efficacy as exendin-4. After single-dose administration in ICR mice, E2HSA showed prolonged glucose lowering effects which lasted up to four days and extended inhibition on gastric emptying for at least 72 hours. Chronic E2HSA treatment in db/db mice significantly improved glucose tolerance, reduced elevated nonfasting and fasting plasma glucose levels, and also decreased HbA1c levels. E2HSA also increased insulin secretion and decreased body weight and appetite. Furthermore, immunofluorescence analysis showed that E2HSA increased beta-cell area, improved islet morphology, and reduced beta-cell apoptosis. In accordance with the promotion of beta-cell function and survival, E2HSA upregulated genes such as Irs2, Pdx-1, Nkx6.1, and MafA and downregulated the expression levels of FoxO1 and proapoptotic Bcl-2 family proteins. In conclusion, with prolonged glucose lowering effects and promoting beta-cell function and survival, the fusion protein, E2HSA, is a promising new therapeutic for once weekly treatment of type 2 diabetes. PMID- 26351644 TI - Impact of Pneumococcal Conjugate Universal Routine Vaccination on Pneumococcal Disease in Italian Children. AB - In Italy, the effectiveness of pneumococcal universal vaccination in preventing vaccine-type invasive pneumococcal disease (IPD) in the PCV7/PCV13 shifting period was estimated to be 84.3% (95% CI: 84.0-84.6%) in children <5 years. This study aims at corroborating the estimation of both the effectiveness (VE) of PCVs and its impact in reducing pneumococcal diseases. A 1:3 matched-case-control study was conducted among children <5 years old hospitalized for IPD or pneumococcal pneumonia (PP) between 2006 and 2012 in the Puglia region. Moreover, hospitalizations for pneumococcal outcomes in the pre- and postvaccination period and the hospitalization risk ratios (HRRs) with 95% CIs were computed in Italy and in the first eight regions that introduced PCVs in 2006. The overall effectiveness of PCVs was 75% (95% CI: 61%-84%); it was 69% (95% CI: 30%-88%) against IPD and 77% (95% CI: 61%-87%) against PP. PCVs showed a significant impact on IPD and acute otitis media either at a national level or in those regions with a longer vaccination history, with a nearly 40% reduction of hospitalizations for both outcomes. Our findings provide further evidence of the effectiveness of PCVs against pneumococcal diseases and its impact on nasopharyngeal carriage in children <5 years, indicating the importance of maintaining high immunization coverage. PMID- 26351645 TI - Meningococcal Antigen Typing System Development and Application to the Evaluation of Effectiveness of Meningococcal B Vaccine and Possible Use for Other Purposes. AB - Development of the 4-component meningococcal serogroup B vaccine (4CMenB) has required new assays for the reliable evaluation of the expression and cross reactivity of those specific antigen variants that are predicted to be targeted by bactericidal antibodies elicited by the vaccine in different isolates. Existing laboratory techniques, such as multilocus sequence typing, are poorly suited to this purpose, since they do not provide information on the contribution of single vaccine components and therefore cannot be applied to estimate the potential coverage of the multicomponent vaccine. The hSBA, the only correlate of protection against invasive meningococcal disease accepted thus far, cannot conveniently be used to test large number of strains. To overcome these issues, the meningococcal antigen typing system (MATS) has been specifically developed in order to predict 4CMenB coverage of individual meningococcus serogroup B strains. To date, MATS has proved advantageous for several reasons, including its ability to assess both qualitative and quantitative aspects of surface antigens of single strains in a highly reproducible, rapid, and resource-saving manner, while its shortcomings include a possible underestimation of 4CMenB coverage and the use of pooled sera to calculate the positive bactericidal threshold. This paper provides an overview of MATS development and its field application. PMID- 26351643 TI - How the Knowledge of Interactions between Meningococcus and the Human Immune System Has Been Used to Prepare Effective Neisseria meningitidis Vaccines. AB - In the last decades, tremendous advancement in dissecting the mechanisms of pathogenicity of Neisseria meningitidis at a molecular level has been achieved, exploiting converging approaches of different disciplines, ranging from pathology to microbiology, immunology, and omics sciences (such as genomics and proteomics). Here, we review the molecular biology of the infectious agent and, in particular, its interactions with the immune system, focusing on both the innate and the adaptive responses. Meningococci exploit different mechanisms and complex machineries in order to subvert the immune system and to avoid being killed. Capsular polysaccharide and lipooligosaccharide glycan composition, in particular, play a major role in circumventing immune response. The understanding of these mechanisms has opened new horizons in the field of vaccinology. Nowadays different licensed meningococcal vaccines are available and used: conjugate meningococcal C vaccines, tetravalent conjugate vaccines, an affordable conjugate vaccine against the N. menigitidis serogroup A, and universal vaccines based on multiple antigens each one with a different and peculiar function against meningococcal group B strains. PMID- 26351646 TI - Nasopharyngeal Bacterial Carriage in the Conjugate Vaccine Era with a Focus on Pneumococci. AB - Seven-valent pneumococcal conjugate vaccine (PCV7) was included in the UK national immunisation program in 2006, and this was replaced by thirteen-valent PCV in 2010. During this time, the carriage of vaccine-type Streptococcus pneumoniae decreased but pneumococcal carriage remained stable due to increases in non-vaccine-type S. pneumoniae. Carriage studies have been undertaken in various countries to monitor vaccine-type replacement and to help predict the serotypes, which may cause invasive disease. There has been less focus on how conjugate vaccines indirectly affect colonization of other nasopharyngeal bacteria. If the nasopharynx is treated as a niche, then bacterial dynamics are accepted to occur. Alterations in these dynamics have been shown due to seasonal changes, antibiotic use, and sibling/day care interaction. It has been shown that, following PCV7 introduction, an eradication of pneumococcal vaccine types has resulted in increases in the abundance of other respiratory pathogens including Haemophilus influenzae and Staphylococcus aureus. These changes are difficult to attribute to PCV7 introduction alone and these studies do not account for further changes due to PCV13 implementation. This review aims to describe nasopharyngeal cocarriage of respiratory pathogens in the PCV era. PMID- 26351647 TI - Meningococcal B Vaccination (4CMenB) in Infants and Toddlers. AB - Neisseria meningitidis is a Gram-negative pathogen that actively invades its human host and leads to the development of life-threatening pathologies. One of the leading causes of death in the world, N. meningitidis can be responsible for nearly 1,000 new infections per 100,000 subjects during an epidemic period. The bacterial species are classified into 12 serogroups, five of which (A, B, C, W, and Y) cause the majority of meningitides. The three purified protein conjugate vaccines currently available target serogroups A, C, W, and Y. Serogroup B has long been a challenge but the discovery of the complete genome sequence of an MenB strain has allowed the development of a specific four-component vaccine (4CMenB). This review describes the pathogenetic role of N. meningitidis and the recent literature concerning the new meningococcal vaccine. PMID- 26351648 TI - Impacts of the 13-Valent Pneumococcal Conjugate Vaccine in Children. AB - Applications of the heptavalent pneumococcal conjugate vaccine (PCV7) in the pediatric immunization schedule have dramatically reduced the incidence of pneumococcal diseases in both vaccinated children and unvaccinated individuals of all ages. However, increased infections caused by non-PCV7 serotypes have been reported by several groups. To overcome this problem, new vaccines covering more serotypes including the emerging serotypes have been developed. The 13-valent pneumococcal conjugate vaccine (PCV13) currently covers the 7 PCV7 serotypes (4, 6B, 9V, 14, 18C, 19F, and 23F) and 6 additional serotypes 1, 3, 5, 6A, 7F, and 19A. After the first year of PCV13 applications in the immunization schedule in young children, global evaluation studies demonstrated that PCV13 provided a wider coverage and more effective prevention than PCV7 against invasive pneumococcal diseases (IPDs), mucosal pneumococcal diseases, and pneumococcal carriage. We reviewed the effects of PCV13 in the control of pneumococcal diseases in children based on previous studies. PMID- 26351649 TI - Estimation of the Impact of Meningococcal Serogroup C Universal Vaccination in Italy and Suggestions for the Multicomponent Serogroup B Vaccine Introduction. AB - In Italy, the meningococcal C conjugate vaccine (MenC) has been offered in most regions since 2009-2010. The incidence of Invasive Meningococcal Disease (IMD) was 0.25 confirmed cases per 100,000 in 2011, but this may be considerably underestimated due to underdetection and underreporting. This study estimates the impact of the MenC universal vaccination (URV) in the Puglia region by assessing the completeness of three registration sources (notifications, hospitalizations, and laboratory surveillance). Capture-recapture analysis was performed on meningococcal meningitis collected within 2001-2013. The impact of URV among <= 18-year-olds was assessed by attributable benefit, preventable fraction, and prevented fraction. Missed opportunities for vaccination were evaluated from surveillance of IMD. The proportion of detected serogroups was applied to the number of IMD in the postvaccination period to compute the cases still preventable. The sensitivity of the three sources was 36.7% (95% CI: 17.5%-57.9%) and registrations lost nearly 28 cases/year in the period. Attributable benefit of URV was -0.5 cases per 100,000, preventable fraction 19.6%, and prevented fraction 31.3%. Three adolescent cases missed the opportunity to be vaccinated. The multicomponent serogroup B meningococcal vaccine has the potential to further prevent at least three other cases/year. Vaccination strategy against serogroup B together with existing programmes makes IMD a 100% vaccine-preventable disease. PMID- 26351650 TI - ERRATUM. AB - [This corrects the article DOI: 10.1093/ofid/ofv111.]. PMID- 26351652 TI - Estimating Risk of Natural Gas Portfolios by Using GARCH-EVT-Copula Model. AB - This paper concentrates on estimating the risk of Title Transfer Facility (TTF) Hub natural gas portfolios by using the GARCH-EVT-copula model. We first use the univariate ARMA-GARCH model to model each natural gas return series. Second, the extreme value distribution (EVT) is fitted to the tails of the residuals to model marginal residual distributions. Third, multivariate Gaussian copula and Student t-copula are employed to describe the natural gas portfolio risk dependence structure. Finally, we simulate N portfolios and estimate value at risk (VaR) and conditional value at risk (CVaR). Our empirical results show that, for an equally weighted portfolio of five natural gases, the VaR and CVaR values obtained from the Student t-copula are larger than those obtained from the Gaussian copula. Moreover, when minimizing the portfolio risk, the optimal natural gas portfolio weights are found to be similar across the multivariate Gaussian copula and Student t-copula and different confidence levels. PMID- 26351651 TI - In Vitro and In Vivo Studies of Non-Platinum-Based Halogenated Compounds as Potent Antitumor Agents for Natural Targeted Chemotherapy of Cancers. AB - Based on a molecular-mechanism-based anticancer drug discovery program enabled by an innovative femtomedicine approach, we have found a previously unknown class of non-platinum-based halogenated molecules (called FMD compounds) as potent antitumor agents for effective treatment of cancers. Here, we present in vitro and in vivo studies of the compounds for targeted chemotherapy of cervical, breast, ovarian, and lung cancers. Our results show that these FMD agents led to DNA damage, cell cycle arrest in the S phase, and apoptosis in cancer cells. We also observed that such a FMD compound caused an increase of reduced glutathione (GSH, an endogenous antioxidant) levels in human normal cells, while it largely depleted GSH in cancer cells. We correspondingly found that these FMD agents exhibited no or little toxicity toward normal cells/tissues, while causing significant cytotoxicity against cancer cells, as well as suppression and delay in tumor growth in mouse xenograft models of cervical, ovarian, breast and lung cancers. These compounds are therefore a previously undiscovered class of potent antitumor agents that can be translated into clinical trials for natural targeted chemotherapy of multiple cancers. PMID- 26351653 TI - A Good Beginning Makes a Good Market: The Effect of Different Market Opening Structures on Market Quality. AB - This paper deals with the market structure at the opening of the trading day and its influence on subsequent trading. We compare a single continuous double auction and two complement markets with different call auction designs as opening mechanisms in a unified experimental framework. The call auctions differ with respect to their levels of transparency. We find that a call auction not only improves market efficiency and liquidity at the beginning of the trading day when compared to the stand-alone continuous double auction, but also causes positive spillover effects on subsequent trading. Concerning the design of the opening call auction, we find no significant differences between the transparent and nontransparent specification with respect to opening prices and liquidity. In the course of subsequent continuous trading, however, market quality is slightly higher after a nontransparent call auction. PMID- 26351655 TI - Convexity of Ruin Probability and Optimal Dividend Strategies for a General Levy Process. AB - We consider the optimal dividends problem for a company whose cash reserves follow a general Levy process with certain positive jumps and arbitrary negative jumps. The objective is to find a policy which maximizes the expected discounted dividends until the time of ruin. Under appropriate conditions, we use some recent results in the theory of potential analysis of subordinators to obtain the convexity properties of probability of ruin. We present conditions under which the optimal dividend strategy, among all admissible ones, takes the form of a barrier strategy. PMID- 26351654 TI - Three-Dimensional Finite Element Analysis of Anterior Single Implant-Supported Prostheses with Different Bone Anchorages. AB - The aim of this study was to evaluate the stress distribution of monocortical and bicortical implant placement of external hexagon connection in the anterior region of the maxilla by 3D finite element analysis (FEA). 3D models were simulated to represent a bone block of anterior region of the maxilla containing an implant (4.0 * 10.0 mm) and an implant-supported cemented metalloceramic crown of the central incisor. Different techniques were tested (monocortical, bicortical, and bicortical associated with nasal floor elevation). FEA was performed in FEMAP/NeiNastran software using loads of 178 N at 0 degrees , 30 degrees , and 60 degrees in relation to implant long axis. The von Mises, maximum principal stress, and displacement maps were plotted for evaluation. Similar stress patterns were observed for all models. Oblique loads increased the stress concentration on fixation screws and in the cervical area of the implants and bone around them. Bicortical technique showed less movement tendency in the implant and its components. Cortical bone of apical region showed increase of stress concentration for bicortical techniques. Within the limitations of this study, oblique loading increased the stress concentrations for all techniques. Moreover, bicortical techniques showed the best biomechanical behavior compared with monocortical technique in the anterior maxillary area. PMID- 26351656 TI - An OFDM Receiver with Frequency Domain Diversity Combined Impulsive Noise Canceller for Underwater Network. AB - In order to explore marine natural resources using remote robotic sensor or to enable rapid information exchange between ROV (remotely operated vehicles), AUV (autonomous underwater vehicle), divers, and ships, ultrasonic underwater communication systems are used. However, if the communication system is applied to rich living creature marine environment such as shallow sea, it suffers from generated Impulsive Noise so-called Shrimp Noise, which is randomly generated in time domain and seriously degrades communication performance in underwater acoustic network. With the purpose of supporting high performance underwater communication, a robust digital communication method for Impulsive Noise environments is necessary. In this paper, we propose OFDM ultrasonic communication system with diversity receiver. The main feature of the receiver is a newly proposed Frequency Domain Diversity Combined Impulsive Noise Canceller. The OFDM receiver utilizes 20-28 KHz ultrasonic channel and subcarrier spacing of 46.875 Hz (MODE3) and 93.750 Hz (MODE2) OFDM modulations. In addition, the paper shows Impulsive Noise distribution data measured at a fishing port in Okinawa and at a barge in Shizuoka prefectures and then proposed diversity OFDM transceivers architecture and experimental results are described. By the proposed Impulsive Noise Canceller, frame bit error rate has been decreased by 20-30%. PMID- 26351657 TI - Improved Secret Image Sharing Scheme in Embedding Capacity without Underflow and Overflow. AB - Computational secret image sharing (CSIS) is an effective way to protect a secret image during its transmission and storage, and thus it has attracted lots of attentions since its appearance. Nowadays, it has become a hot topic for researchers to improve the embedding capacity and eliminate the underflow and overflow situations, which is embarrassing and difficult to deal with. The scheme, which has the highest embedding capacity among the existing schemes, has the underflow and overflow problems. Although the underflow and overflow situations have been well dealt with by different methods, the embedding capacities of these methods are reduced more or less. Motivated by these concerns, we propose a novel scheme, in which we take the differential coding, Huffman coding, and data converting to compress the secret image before embedding it to further improve the embedding capacity, and the pixel mapping matrix embedding method with a newly designed matrix is used to embed secret image data into the cover image to avoid the underflow and overflow situations. Experiment results show that our scheme can improve the embedding capacity further and eliminate the underflow and overflow situations at the same time. PMID- 26351658 TI - Security Enhancement Using Cache Based Reauthentication in WiMAX Based E-Learning System. AB - WiMAX networks are the most suitable for E-Learning through their Broadcast and Multicast Services at rural areas. Authentication of users is carried out by AAA server in WiMAX. In E-Learning systems the users must be forced to perform reauthentication to overcome the session hijacking problem. The reauthentication of users introduces frequent delay in the data access which is crucial in delaying sensitive applications such as E-Learning. In order to perform fast reauthentication caching mechanism known as Key Caching Based Authentication scheme is introduced in this paper. Even though the cache mechanism requires extra storage to keep the user credentials, this type of mechanism reduces the 50% of the delay occurring during reauthentication. PMID- 26351659 TI - Periodontal Biological Events Associated with Orthodontic Tooth Movement: The Biomechanics of the Cytoskeleton and the Extracellular Matrix. AB - The mechanical stimuli generated by orthodontic forces cause deformation of extracellular matrices and cells, vascular changes, inflammation, and the release of active biological agents generating a complex multifactorial sequence of biological events culminating in bone remodelling enabling orthodontic tooth movement. Orthodontic forces on the teeth generate stresses in periodontal tissues according to a number of variables including the type (continuous, interrupted, or intermittent), magnitude, direction, and frequency of the applied load. Whether the strain is compressive or tensile determines whether bone deposition or bone resorption will occur. The mechanically induced strains mediate structural changes in extracellular matrices and in cells, consequently affecting cellular gene expression and function. In the extracellular matrix, mechanosensing molecules integrated into the structure of various proteins can be activated upon load-induced protein unfolding. These specialized molecules have the capacity to sense and then to convert microenvironmental biomechanical stimuli into intracellular biochemical signals that interact to generate a coordinated tissue response. It is also possible that the applied force may directly cause nuclear deformation with configurational changes in chromatin, thus influencing gene expression. In this review article we summarize the current general concepts of mechanotransduction influencing the remodelling of periodontal tissues thus enabling tooth movement in response to applied orthodontic loads. PMID- 26351660 TI - Prediction of Domain Behavior through Dynamic Well-Being Domain Model Analysis. AB - As the concept of context-awareness is becoming more popular the demand for improved quality of context-aware systems increases too. Due to the inherent challenges posed by context-awareness, it is harder to predict what the behavior of the systems and their context will be once provided to the end-user than is the case for non-context-aware systems. A domain where such upfront knowledge is highly important is that of well-being. In this paper, we introduce a method to model the well-being domain and to predict the effects the system will have on its context when implemented. This analysis can be performed at design time. Using these predictions, the design can be fine-tuned to increase the chance that systems will have the desired effect. The method has been tested using three existing well-being applications. For these applications, domain models were created in the Dynamic Well-being Domain Model language. This language allows for causal reasoning over the application domain. The models created were used to perform the analysis and behavior prediction. The analysis results were compared to existing application end-user evaluation studies. Results showed that our analysis could accurately predict success and possible problems in the focus of the systems, although certain limitation regarding the predictions should be kept into consideration. PMID- 26351661 TI - Gut DNA viromes of Malawian twins discordant for severe acute malnutrition. AB - The bacterial component of the human gut microbiota undergoes a definable program of postnatal development. Evidence is accumulating that this program is disrupted in children with severe acute malnutrition (SAM) and that their persistent gut microbiota immaturity, which is not durably repaired with current ready-to-use therapeutic food (RUTF) interventions, is causally related to disease pathogenesis. To further characterize gut microbial community development in healthy versus malnourished infants/children, we performed a time-series metagenomic study of DNA isolated from virus-like particles (VLPs) recovered from fecal samples collected during the first 30 mo of postnatal life from eight pairs of mono- and dizygotic Malawian twins concordant for healthy growth and 12 twin pairs discordant for SAM. Both members of discordant pairs were sampled just before, during, and after treatment with a peanut-based RUTF. Using Random Forests and a dataset of 17,676 viral contigs assembled from shotgun sequencing reads of VLP DNAs, we identified viruses that distinguish different stages in the assembly of the gut microbiota in the concordant healthy twin pairs. This developmental program is impaired in both members of SAM discordant pairs and not repaired with RUTF. Phage plus members of the Anelloviridae and Circoviridae families of eukaryotic viruses discriminate discordant from concordant healthy pairs. These results disclose that apparently healthy cotwins in discordant pairs have viromes associated with, although not necessarily mediators, of SAM; as such, they provide a human model for delineating normal versus perturbed postnatal acquisition and retention of the gut microbiota's viral component in populations at risk for malnutrition. PMID- 26351662 TI - Impact of human mobility on the emergence of dengue epidemics in Pakistan. AB - The recent emergence of dengue viruses into new susceptible human populations throughout Asia and the Middle East, driven in part by human travel on both local and global scales, represents a significant global health risk, particularly in areas with changing climatic suitability for the mosquito vector. In Pakistan, dengue has been endemic for decades in the southern port city of Karachi, but large epidemics in the northeast have emerged only since 2011. Pakistan is therefore representative of many countries on the verge of countrywide endemic dengue transmission, where prevention, surveillance, and preparedness are key priorities in previously dengue-free regions. We analyze spatially explicit dengue case data from a large outbreak in Pakistan in 2013 and compare the dynamics of the epidemic to an epidemiological model of dengue virus transmission based on climate and mobility data from ~40 million mobile phone subscribers. We find that mobile phone-based mobility estimates predict the geographic spread and timing of epidemics in both recently epidemic and emerging locations. We combine transmission suitability maps with estimates of seasonal dengue virus importation to generate fine-scale dynamic risk maps with direct application to dengue containment and epidemic preparedness. PMID- 26351663 TI - Neighborhood effects on use of African-American Vernacular English. AB - African-American Vernacular English (AAVE) is systematic, rooted in history, and important as an identity marker and expressive resource for its speakers. In these respects, it resembles other vernacular or nonstandard varieties, like Cockney or Appalachian English. But like them, AAVE can trigger discrimination in the workplace, housing market, and schools. Understanding what shapes the relative use of AAVE vs. Standard American English (SAE) is important for policy and scientific reasons. This work presents, to our knowledge, the first experimental estimates of the effects of moving into lower-poverty neighborhoods on AAVE use. We use data on non-Hispanic African-American youth (n = 629) from a large-scale, randomized residential mobility experiment called Moving to Opportunity (MTO), which enrolled a sample of mostly minority families originally living in distressed public housing. Audio recordings of the youth were transcribed and coded for the use of five grammatical and five phonological AAVE features to construct a measure of the proportion of possible instances, or tokens, in which speakers use AAVE rather than SAE speech features. Random assignment to receive a housing voucher to move into a lower-poverty area (the intention-to-treat effect) led youth to live in neighborhoods (census tracts) with an 11 percentage point lower poverty rate on average over the next 10-15 y and reduced the share of AAVE tokens by ~3 percentage points compared with the MTO control group youth. The MTO effect on AAVE use equals approximately half of the difference in AAVE frequency observed between youth whose parents have a high school diploma and those whose parents do not. PMID- 26351664 TI - In-depth study of Mollivirus sibericum, a new 30,000-y-old giant virus infecting Acanthamoeba. AB - Acanthamoeba species are infected by the largest known DNA viruses. These include icosahedral Mimiviruses, amphora-shaped Pandoraviruses, and Pithovirus sibericum, the latter one isolated from 30,000-y-old permafrost. Mollivirus sibericum, a fourth type of giant virus, was isolated from the same permafrost sample. Its approximately spherical virion (0.6-um diameter) encloses a 651-kb GC-rich genome encoding 523 proteins of which 64% are ORFans; 16% have their closest homolog in Pandoraviruses and 10% in Acanthamoeba castellanii probably through horizontal gene transfer. The Mollivirus nucleocytoplasmic replication cycle was analyzed using a combination of "omic" approaches that revealed how the virus highjacks its host machinery to actively replicate. Surprisingly, the host's ribosomal proteins are packaged in the virion. Metagenomic analysis of the permafrost sample uncovered the presence of both viruses, yet in very low amount. The fact that two different viruses retain their infectivity in prehistorical permafrost layers should be of concern in a context of global warming. Giant viruses' diversity remains to be fully explored. PMID- 26351665 TI - Ancient genomes link early farmers from Atapuerca in Spain to modern-day Basques. AB - The consequences of the Neolithic transition in Europe--one of the most important cultural changes in human prehistory--is a subject of great interest. However, its effect on prehistoric and modern-day people in Iberia, the westernmost frontier of the European continent, remains unresolved. We present, to our knowledge, the first genome-wide sequence data from eight human remains, dated to between 5,500 and 3,500 years before present, excavated in the El Portalon cave at Sierra de Atapuerca, Spain. We show that these individuals emerged from the same ancestral gene pool as early farmers in other parts of Europe, suggesting that migration was the dominant mode of transferring farming practices throughout western Eurasia. In contrast to central and northern early European farmers, the Chalcolithic El Portalon individuals additionally mixed with local southwestern hunter-gatherers. The proportion of hunter-gatherer-related admixture into early farmers also increased over the course of two millennia. The Chalcolithic El Portalon individuals showed greatest genetic affinity to modern-day Basques, who have long been considered linguistic and genetic isolates linked to the Mesolithic whereas all other European early farmers show greater genetic similarity to modern-day Sardinians. These genetic links suggest that Basques and their language may be linked with the spread of agriculture during the Neolithic. Furthermore, all modern-day Iberian groups except the Basques display distinct admixture with Caucasus/Central Asian and North African groups, possibly related to historical migration events. The El Portalon genomes uncover important pieces of the demographic history of Iberia and Europe and reveal how prehistoric groups relate to modern-day people. PMID- 26351666 TI - Rapid and transient palmitoylation of the tyrosine kinase Lck mediates Fas signaling. AB - Palmitoylation is the posttranslational modification of proteins with a 16-carbon fatty acid chain through a labile thioester bond. The reversibility of protein palmitoylation and its profound effect on protein function suggest that this modification could play an important role as an intracellular signaling mechanism. Evidence that palmitoylation of proteins occurs with the kinetics required for signal transduction is not clear, however. Here we show that engagement of the Fas receptor by its ligand leads to an extremely rapid and transient increase in palmitoylation levels of the tyrosine kinase Lck. Lck palmitoylation kinetics are consistent with the activation of downstream signaling proteins, such as Zap70 and PLC-gamma1. Inhibiting Lck palmitoylation not only disrupts proximal Fas signaling events, but also renders cells resistant to Fas-mediated apoptosis. Knockdown of the palmitoyl acyl transferase DHHC21 eliminates activation of Lck and downstream signaling after Fas receptor stimulation. Our findings demonstrate highly dynamic Lck palmitoylation kinetics that are essential for signaling downstream of the Fas receptor. PMID- 26351667 TI - Accelerating molecular simulations of proteins using Bayesian inference on weak information. AB - Atomistic molecular dynamics (MD) simulations of protein molecules are too computationally expensive to predict most native structures from amino acid sequences. Here, we integrate "weak" external knowledge into folding simulations to predict protein structures, given their sequence. For example, we instruct the computer "to form a hydrophobic core," "to form good secondary structures," or "to seek a compact state." This kind of information has been too combinatoric, nonspecific, and vague to help guide MD simulations before. Within atomistic replica-exchange molecular dynamics (REMD), we develop a statistical mechanical framework, modeling using limited data with coarse physical insight(s) (MELD + CPI), for harnessing weak information. As a test, we apply MELD + CPI to predict the native structures of 20 small proteins. MELD + CPI samples to within less than 3.2 A from native for all 20 and correctly chooses the native structures (<4 A) for 15 of them, including ubiquitin, a millisecond folder. MELD + CPI is up to five orders of magnitude faster than brute-force MD, satisfies detailed balance, and should scale well to larger proteins. MELD + CPI may be useful where physics based simulations are needed to study protein mechanisms and populations and where we have some heuristic or coarse physical knowledge about states of interest. PMID- 26351668 TI - Topological patterns in two-dimensional gel electrophoresis of DNA knots. AB - Gel electrophoresis is a powerful experimental method to probe the topology of DNA and other biopolymers. Although there is a large body of experimental work that allows us to accurately separate different topoisomers of a molecule, a full theoretical understanding of these experiments has not yet been achieved. Here we show that the mobility of DNA knots depends crucially and subtly on the physical properties of the gel and, in particular, on the presence of dangling ends. The topological interactions between these and DNA molecules can be described in terms of an "entanglement number" and yield a nonmonotonic mobility at moderate fields. Consequently, in 2D electrophoresis, gel bands display a characteristic arc pattern; this turns into a straight line when the density of dangling ends vanishes. We also provide a novel framework to accurately predict the shape of such arcs as a function of molecule length and topological complexity, which may be used to inform future experiments. PMID- 26351669 TI - TNF-alpha-stimulated fibroblasts secrete lumican to promote fibrocyte differentiation. AB - In healing wounds and fibrotic lesions, fibroblasts and monocyte-derived fibroblast-like cells called fibrocytes help to form scar tissue. Although fibrocytes promote collagen production by fibroblasts, little is known about signaling from fibroblasts to fibrocytes. In this report, we show that fibroblasts stimulated with the fibrocyte-secreted inflammatory signal tumor necrosis factor-alpha secrete the small leucine-rich proteoglycan lumican, and that lumican, but not the related proteoglycan decorin, promotes human fibrocyte differentiation. Lumican competes with the serum fibrocyte differentiation inhibitor serum amyloid P, but dominates over the fibroblast-secreted fibrocyte inhibitor Slit2. Lumican acts directly on monocytes, and unlike other factors that affect fibrocyte differentiation, lumican has no detectable effect on macrophage differentiation or polarization. alpha2beta1, alphaMbeta2, and alphaXbeta2 integrins are needed for lumican-induced fibrocyte differentiation. In lung tissue from pulmonary fibrosis patients with relatively normal lung function, lumican is present at low levels throughout the tissue, whereas patients with advanced disease have pronounced lumican expression in the fibrotic lesions. These data may explain why fibrocytes are increased in fibrotic tissues, suggest that the levels of lumican in tissues may have a significant effect on the decision of monocytes to differentiate into fibrocytes, and indicate that modulating lumican signaling may be useful as a therapeutic for fibrosis. PMID- 26351670 TI - Isoflurane inhibits synaptic vesicle exocytosis through reduced Ca2+ influx, not Ca2+-exocytosis coupling. AB - Identifying presynaptic mechanisms of general anesthetics is critical to understanding their effects on synaptic transmission. We show that the volatile anesthetic isoflurane inhibits synaptic vesicle (SV) exocytosis at nerve terminals in dissociated rat hippocampal neurons through inhibition of presynaptic Ca(2+) influx without significantly altering the Ca(2+) sensitivity of SV exocytosis. A clinically relevant concentration of isoflurane (0.7 mM) inhibited changes in [Ca(2+)]i driven by single action potentials (APs) by 25 +/- 3%, which in turn led to 62 +/- 3% inhibition of single AP-triggered exocytosis at 4 mM extracellular Ca(2+) ([Ca(2+)]e). Lowering external Ca(2+) to match the isoflurane-induced reduction in Ca(2+) entry led to an equivalent reduction in exocytosis. These data thus indicate that anesthetic inhibition of neurotransmitter release from small SVs occurs primarily through reduced axon terminal Ca(2+) entry without significant direct effects on Ca(2+)-exocytosis coupling or on the SV fusion machinery. Isoflurane inhibition of exocytosis and Ca(2+) influx was greater in glutamatergic compared with GABAergic nerve terminals, consistent with selective inhibition of excitatory synaptic transmission. Such alteration in the balance of excitatory to inhibitory transmission could mediate reduced neuronal interactions and network-selective effects observed in the anesthetized central nervous system. PMID- 26351671 TI - Glass-to-cryogenic-liquid transitions in aqueous solutions suggested by crack healing. AB - Observation of theorized glass-to-liquid transitions between low-density amorphous (LDA) and high-density amorphous (HDA) water states had been stymied by rapid crystallization below the homogeneous water nucleation temperature (~235 K at 0.1 MPa). We report optical and X-ray observations suggestive of glass-to liquid transitions in these states. Crack healing, indicative of liquid, occurs when LDA ice transforms to cubic ice at 160 K, and when HDA ice transforms to the LDA state at temperatures as low as 120 K. X-ray diffraction study of the HDA to LDA transition clearly shows the characteristics of a first-order transition. Study of the glass-to-liquid transitions in nanoconfined aqueous solutions shows them to be independent of the solute concentrations, suggesting that they represent an intrinsic property of water. These findings support theories that LDA and HDA ice are thermodynamically distinct and that they are continuously connected to two different liquid states of water. PMID- 26351672 TI - Transcellular spreading of huntingtin aggregates in the Drosophila brain. AB - A key feature of many neurodegenerative diseases is the accumulation and subsequent aggregation of misfolded proteins. Recent studies have highlighted the transcellular propagation of protein aggregates in several major neurodegenerative diseases, although the precise mechanisms underlying this spreading and how it relates to disease pathology remain unclear. Here we use a polyglutamine-expanded form of human huntingtin (Htt) with a fluorescent tag to monitor the spreading of aggregates in the Drosophila brain in a model of Huntington's disease. Upon expression of this construct in a defined subset of neurons, we demonstrate that protein aggregates accumulate at synaptic terminals and progressively spread throughout the brain. These aggregates are internalized and accumulate within other neurons. We show that Htt aggregates cause non-cell autonomous pathology, including loss of vulnerable neurons that can be prevented by inhibiting endocytosis in these neurons. Finally we show that the release of aggregates requires N-ethylmalemide-sensitive fusion protein 1, demonstrating that active release and uptake of Htt aggregates are important elements of spreading and disease progression. PMID- 26351674 TI - Multistep food plant processing at Grotta Paglicci (Southern Italy) around 32,600 cal B.P. AB - Residue analyses on a grinding tool recovered at Grotta Paglicci sublayer 23A [32,614 +/- 429 calibrated (cal) B.P.], Southern Italy, have demonstrated that early modern humans collected and processed various plants. The recording of starch grains attributable to Avena (oat) caryopses expands our information about the food plants used for producing flour in Europe during the Paleolithic and about the origins of a food tradition persisting up to the present in the Mediterranean basin. The quantitative distribution of the starch grains on the surface of the grinding stone furnished information about the tool handling, confirming its use as a pestle-grinder, as suggested by the wear-trace analysis. The particular state of preservation of the starch grains suggests the use of a thermal treatment before grinding, possibly to accelerate drying of the plants, making the following process easier and faster. The study clearly indicates that the exploitation of plant resources was very important for hunter-gatherer populations, to the point that the Early Gravettian inhabitants of Paglicci were able to process food plants and already possessed a wealth of knowledge that was to become widespread after the dawn of agriculture. PMID- 26351673 TI - Fibroblast growth factor 9 is a novel modulator of negative affect. AB - Both gene expression profiling in postmortem human brain and studies using animal models have implicated the fibroblast growth factor (FGF) family in affect regulation and suggest a potential role in the pathophysiology of major depressive disorder (MDD). FGF2, the most widely characterized family member, is down-regulated in the depressed brain and plays a protective role in rodent models of affective disorders. By contrast, using three microarray analyses followed by quantitative RT-PCR confirmation, we show that FGF9 expression is up regulated in the hippocampus of individuals with MDD, and that FGF9 expression is inversely related to the expression of FGF2. Because little is known about FGF9's function in emotion regulation, we used animal models to shed light on its potential role in affective function. We found that chronic social defeat stress, an animal model recapitulating some aspects of MDD, leads to a significant increase in hippocampal FGF9 expression, paralleling the elevations seen in postmortem human brain tissue. Chronic intracerebroventricular administration of FGF9 increased both anxiety- and depression-like behaviors. In contrast, knocking down FGF9 expression in the dentate gyrus of the hippocampus using a lentiviral vector produced a decrease in FGF9 expression and ameliorated anxiety-like behavior. Collectively, these results suggest that high levels of hippocampal FGF9 play an important role in the development or expression of mood and anxiety disorders. We propose that the relative levels of FGF9 in relation to other members of the FGF family may prove key to understanding vulnerability or resilience in affective disorders. PMID- 26351675 TI - Hyperglycemia impairs left-right axis formation and thereby disturbs heart morphogenesis in mouse embryos. AB - Congenital heart defects with heterotaxia are associated with pregestational diabetes mellitus. To provide insight into the mechanisms underlying such diabetes-related heart defects, we examined the effects of high-glucose concentrations on formation of the left-right axis in mouse embryos. Expression of Pitx2, which plays a key role in left-right asymmetric morphogenesis and cardiac development, was lost in the left lateral plate mesoderm of embryos of diabetic dams. Embryos exposed to high-glucose concentrations in culture also failed to express Nodal and Pitx2 in the left lateral plate mesoderm. The distribution of phosphorylated Smad2 revealed that Nodal activity in the node was attenuated, accounting for the failure of left-right axis formation. Consistent with this notion, Notch signal-dependent expression of Nodal-related genes in the node was also down-regulated in association with a reduced level of Notch signaling, suggesting that high-glucose concentrations impede Notch signaling and thereby hinder establishment of the left-right axis required for heart morphogenesis. PMID- 26351676 TI - Requirement for transient metal ions revealed through computational analysis for DNA polymerase going in reverse. AB - DNA polymerases facilitate faithful insertion of nucleotides, a central reaction occurring during DNA replication and repair. DNA synthesis (forward reaction) is "balanced," as dictated by the chemical equilibrium by the reverse reaction of pyrophosphorolysis. Two closely spaced divalent metal ions (catalytic and nucleotide-binding metals) provide the scaffold for these reactions. The catalytic metal lowers the pKa of O3' of the growing primer terminus, and the nucleotide-binding metal facilitates substrate binding. Recent time-lapse crystallographic studies of DNA polymerases have identified an additional metal ion (product metal) associated with pyrophosphate formation, leading to the suggestion of its possible involvement in the reverse reaction. Here, we establish a rationale for a role of the product metal using quantum mechanical/molecular mechanical calculations of the reverse reaction in the confines of the DNA polymerase beta active site. Additionally, site-directed mutagenesis identifies essential residues and metal-binding sites necessary for pyrophosphorolysis. The results indicate that the catalytic metal site must be occupied by a magnesium ion for pyrophosphorolysis to occur. Critically, the product metal site is occupied by a magnesium ion early in the pyrophosphorolysis reaction path but must be removed later. The proposed dynamic nature of the active site metal ions is consistent with crystallographic structures. The transition barrier for pyrophosphorolysis was estimated to be significantly higher than that for the forward reaction, consistent with kinetic activity measurements of the respective reactions. These observations provide a framework to understand how ions and active site changes could modulate the internal chemical equilibrium of a reaction that is central to genome stability. PMID- 26351677 TI - Hopanoids as functional analogues of cholesterol in bacterial membranes. AB - The functionality of cellular membranes relies on the molecular order imparted by lipids. In eukaryotes, sterols such as cholesterol modulate membrane order, yet they are not typically found in prokaryotes. The structurally similar bacterial hopanoids exhibit similar ordering properties as sterols in vitro, but their exact physiological role in living bacteria is relatively uncharted. We present evidence that hopanoids interact with glycolipids in bacterial outer membranes to form a highly ordered bilayer in a manner analogous to the interaction of sterols with sphingolipids in eukaryotic plasma membranes. Furthermore, multidrug transport is impaired in a hopanoid-deficient mutant of the gram-negative Methylobacterium extorquens, which introduces a link between membrane order and an energy-dependent, membrane-associated function in prokaryotes. Thus, we reveal a convergence in the architecture of bacterial and eukaryotic membranes and implicate the biosynthetic pathways of hopanoids and other order-modulating lipids as potential targets to fight pathogenic multidrug resistance. PMID- 26351678 TI - Piezo1 regulates mechanotransductive release of ATP from human RBCs. AB - Piezo proteins (Piezo1 and Piezo2) are recently identified mechanically activated cation channels in eukaryotic cells and associated with physiological responses to touch, pressure, and stretch. In particular, human RBCs express Piezo1 on their membranes, and mutations of Piezo1 have been linked to hereditary xerocytosis. To date, however, physiological functions of Piezo1 on normal RBCs remain poorly understood. Here, we show that Piezo1 regulates mechanotransductive release of ATP from human RBCs by controlling the shear-induced calcium (Ca(2+)) influx. We find that, in human RBCs treated with Piezo1 inhibitors or having mutant Piezo1 channels, the amounts of shear-induced ATP release and Ca(2+) influx decrease significantly. Remarkably, a critical extracellular Ca(2+) concentration is required to trigger significant ATP release, but membrane associated ATP pools in RBCs also contribute to the release of ATP. Our results show how Piezo1 channels are likely to function in normal RBCs and suggest a previously unidentified mechanotransductive pathway in ATP release. Thus, we anticipate that the study will impact broadly on the research of red cells, cellular mechanosensing, and clinical studies related to red cell disorders and vascular disease. PMID- 26351679 TI - Targeting protein translation, RNA splicing, and degradation by morpholino-based conjugates in Plasmodium falciparum. AB - Identification and genetic validation of new targets from available genome sequences are critical steps toward the development of new potent and selective antimalarials. However, no methods are currently available for large-scale functional analysis of the Plasmodium falciparum genome. Here we present evidence for successful use of morpholino oligomers (MO) to mediate degradation of target mRNAs or to inhibit RNA splicing or translation of several genes of P. falciparum involved in chloroquine transport, apicoplast biogenesis, and phospholipid biosynthesis. Consistent with their role in the parasite life cycle, down regulation of these essential genes resulted in inhibition of parasite development. We show that a MO conjugate that targets the chloroquine-resistant transporter PfCRT is effective against chloroquine-sensitive and -resistant parasites, causes enlarged digestive vacuoles, and renders chloroquine-resistant strains more sensitive to chloroquine. Similarly, we show that a MO conjugate that targets the PfDXR involved in apicoplast biogenesis inhibits parasite growth and that this defect can be rescued by addition of isopentenyl pyrophosphate. MO based gene regulation is a viable alternative approach to functional analysis of the P. falciparum genome. PMID- 26351680 TI - Unique potential of 4-1BB agonist antibody to promote durable regression of HPV+ tumors when combined with an E6/E7 peptide vaccine. AB - Antibody modulation of T-cell coinhibitory (e.g., CTLA-4) or costimulatory (e.g., 4-1BB) receptors promotes clinical responses to a variety of cancers. Therapeutic cancer vaccination, in contrast, has produced limited clinical benefit and no curative therapies. The E6 and E7 oncoproteins of human papilloma virus (HPV) drive the majority of genital cancers, and many oropharyngeal tumors. We discovered 15-19 amino acid peptides from HPV-16 E6/E7 for which induction of T cell immunity correlates with disease-free survival in patients treated for high grade cervical neoplasia. We report here that intranasal vaccination with these peptides and the adjuvant alpha-galactosylceramide elicits systemic and mucosal T cell responses leading to reduced HPV(+) TC-1 tumor growth and prolonged survival in mice. We hypothesized that the inability of these T cells to fully reject established tumors resulted from suppression in the tumor microenvironment which could be ameliorated through checkpoint modulation. Combining this E6/E7 peptide vaccine with checkpoint blockade produced only modest benefit; however, coadministration with a 4-1BB agonist antibody promoted durable regression of established genital TC-1 tumors. Relative to other therapies tested, this combination of vaccine and alpha4-1BB promoted the highest CD8(+) versus regulatory FoxP3(+) T-cell ratios, elicited 2- to 5-fold higher infiltration by E7-specific CTL, and evoked higher densities of highly cytotoxic TcEO (T cytotoxic Eomesodermin) CD8 (>70-fold) and ThEO (T helper Eomesodermin) CD4 (>17 fold) T cells. These findings have immediate clinical relevance both in terms of the direct clinical utility of the vaccine studied and in illustrating the potential of 4-1BB antibody to convert therapeutic E6/E7 vaccines already in clinical trials into curative therapies. PMID- 26351681 TI - Systematic analysis of asymmetric partitioning of yeast proteome between mother and daughter cells reveals "aging factors" and mechanism of lifespan asymmetry. AB - Budding yeast divides asymmetrically, giving rise to a mother cell that progressively ages and a daughter cell with full lifespan. It is generally assumed that mother cells retain damaged, lifespan limiting materials ("aging factors") through asymmetric division. However, the identity of these aging factors and the mechanisms through which they limit lifespan remain poorly understood. Using a flow cytometry-based, high-throughput approach, we quantified the asymmetric partitioning of the yeast proteome between mother and daughter cells during cell division, discovering 74 mother-enriched and 60 daughter enriched proteins. While daughter-enriched proteins are biased toward those needed for bud construction and genome maintenance, mother-enriched proteins are biased towards those localized in the plasma membrane and vacuole. Deletion of 23 of the 74 mother-enriched proteins leads to lifespan extension, a fraction that is about six times that of the genes picked randomly from the genome. Among these lifespan-extending genes, three are involved in endosomal sorting/endosome to vacuole transport, and three are nitrogen source transporters. Tracking the dynamic expression of specific mother-enriched proteins revealed that their concentration steadily increases in the mother cells as they age, but is kept relatively low in the daughter cells via asymmetric distribution. Our results suggest that some mother-enriched proteins may increase to a concentration that becomes deleterious and lifespan-limiting in aged cells, possibly by upsetting homeostasis or leading to aberrant signaling. Our study provides a comprehensive resource for analyzing asymmetric cell division and aging in yeast, which should also be valuable for understanding similar phenomena in other organisms. PMID- 26351682 TI - Can the impact of human genetic variations be predicted? PMID- 26351683 TI - Spatiotemporal distribution of Holocene populations in North America. AB - As the Cordilleran and Laurentide Ice Sheets retreated, North America was colonized by human populations; however, the spatial patterns of subsequent population growth are unclear. Temporal frequency distributions of aggregated radiocarbon ((14)C) dates are used as a proxy of population size and can be used to track this expansion. The Canadian Archaeological Radiocarbon Database contains more than 35,000 (14)C dates and is used in this study to map the spatiotemporal demographic changes of Holocene populations in North America at a continental scale for the past 13,000 y. We use the kernel method, which converts the spatial distribution of (14)C dates into estimates of population density at 500-y intervals. The resulting maps reveal temporally distinct, dynamic patterns associated with paleodemographic trends that correspond well to genetic, archaeological, and ethnohistoric evidence of human occupation. These results have implications for hypothesizing and testing migration routes into and across North America as well as the relative influence of North American populations on the evolution of the North American ecosystem. PMID- 26351684 TI - Dissecting repulsion linkage in the dwarfing gene Dw3 region for sorghum plant height provides insights into heterosis. AB - Heterosis is a main contributor to yield increase in many crop species. Different mechanisms have been proposed for heterosis: dominance, overdominance, epistasis, epigenetics, and protein metabolite changes. However, only limited examples of molecular dissection and validation of these mechanisms are available. Here, we present an example of discovery and validation of heterosis generated by a combination of repulsion linkage and dominance. Using a recombinant inbred line population, a separate quantitative trait locus (QTL) for plant height (qHT7.1) was identified near the genomic region harboring the known auxin transporter Dw3 gene. With two loci having repulsion linkage between two inbreds, heterosis in the hybrid can appear as a single locus with an overdominance mode of inheritance (i.e., pseudo-overdominance). Individually, alleles conferring taller plant height exhibited complete dominance over alleles conferring shorter height. Detailed analyses of different height components demonstrated that qHT7.1 affects both the upper and lower parts of the plant, whereas Dw3 affects only the part below the flag leaf. Computer simulations show that repulsion linkage could influence QTL detection and estimation of effect in segregating populations. Guided by findings in linkage mapping, a genome-wide association study of plant height with a sorghum diversity panel pinpointed genomic regions underlying the trait variation, including Dw1, Dw2, Dw3, Dw4, and qHT7.1. Multilocus mixed model analysis confirmed the advantage of complex trait dissection using an integrated approach. Besides identifying a specific genetic example of heterosis, our research indicated that integrated molecular dissection of complex traits in different population types can enable plant breeders to fine tune the breeding process for crop production. PMID- 26351685 TI - Fossil hominin shoulders support an African ape-like last common ancestor of humans and chimpanzees. AB - Reconstructing the behavioral shifts that drove hominin evolution requires knowledge of the timing, magnitude, and direction of anatomical changes over the past ~6-7 million years. These reconstructions depend on assumptions regarding the morphotype of the Homo-Pan last common ancestor (LCA). However, there is little consensus for the LCA, with proposed models ranging from African ape to orangutan or generalized Miocene ape-like. The ancestral state of the shoulder is of particular interest because it is functionally associated with important behavioral shifts in hominins, such as reduced arboreality, high-speed throwing, and tool use. However, previous morphometric analyses of both living and fossil taxa have yielded contradictory results. Here, we generated a 3D morphospace of ape and human scapular shape to plot evolutionary trajectories, predict ancestral morphologies, and directly test alternative evolutionary hypotheses using the hominin fossil evidence. We show that the most parsimonious model for the evolution of hominin shoulder shape starts with an African ape-like ancestral state. We propose that the shoulder evolved gradually along a single morphocline, achieving modern human-like configuration and function within the genus Homo. These data are consistent with a slow, progressive loss of arboreality and increased tool use throughout human evolution. PMID- 26351686 TI - Loop recognition and copper-mediated disulfide reduction underpin metal site assembly of CuA in human cytochrome oxidase. AB - Maturation of cytochrome oxidases is a complex process requiring assembly of several subunits and adequate uptake of the metal cofactors. Two orthologous Sco proteins (Sco1 and Sco2) are essential for the correct assembly of the dicopper CuA site in the human oxidase, but their function is not fully understood. Here, we report an in vitro biochemical study that shows that Sco1 is a metallochaperone that selectively transfers Cu(I) ions based on loop recognition, whereas Sco2 is a copper-dependent thiol reductase of the cysteine ligands in the oxidase. Copper binding to Sco2 is essential to elicit its redox function and as a guardian of the reduced state of its own cysteine residues in the oxidizing environment of the mitochondrial intermembrane space (IMS). These results provide a detailed molecular mechanism for CuA assembly, suggesting that copper and redox homeostasis are intimately linked in the mitochondrion. PMID- 26351687 TI - Grandmothering life histories and human pair bonding. AB - The evolution of distinctively human life history and social organization is generally attributed to paternal provisioning based on pair bonds. Here we develop an alternative argument that connects the evolution of human pair bonds to the male-biased mating sex ratios that accompanied the evolution of human life history. We simulate an agent-based model of the grandmother hypothesis, compare simulated sex ratios to data on great apes and human hunter-gatherers, and note associations between a preponderance of males and mate guarding across taxa. Then we explore a recent model that highlights the importance of mating sex ratios for differences between birds and mammals and conclude that lessons for human evolution cannot ignore mammalian reproductive constraints. In contradiction to our claim that male-biased sex ratios are characteristically human, female-biased ratios are reported in some populations. We consider the likelihood that fertile men are undercounted and conclude that the mate-guarding hypothesis for human pair bonds gains strength from explicit links with our grandmothering life history. PMID- 26351688 TI - Freshwater discharges drive high levels of methylmercury in Arctic marine biota. AB - Elevated levels of neurotoxic methylmercury in Arctic food-webs pose health risks for indigenous populations that consume large quantities of marine mammals and fish. Estuaries provide critical hunting and fishing territory for these populations, and, until recently, benthic sediment was thought to be the main methylmercury source for coastal fish. New hydroelectric developments are being proposed in many northern ecosystems, and the ecological impacts of this industry relative to accelerating climate changes are poorly characterized. Here we evaluate the competing impacts of climate-driven changes in northern ecosystems and reservoir flooding on methylmercury production and bioaccumulation through a case study of a stratified sub-Arctic estuarine fjord in Labrador, Canada. Methylmercury bioaccumulation in zooplankton is higher than in midlatitude ecosystems. Direct measurements and modeling show that currently the largest methylmercury source is production in oxic surface seawater. Water-column methylation is highest in stratified surface waters near the river mouth because of the stimulating effects of terrestrial organic matter on methylating microbes. We attribute enhanced biomagnification in plankton to a thin layer of marine snow widely observed in stratified systems that concentrates microbial methylation and multiple trophic levels of zooplankton in a vertically restricted zone. Large freshwater inputs and the extensive Arctic Ocean continental shelf mean these processes are likely widespread and will be enhanced by future increases in water column stratification, exacerbating high biological methylmercury concentrations. Soil flooding experiments indicate that near-term changes expected from reservoir creation will increase methylmercury inputs to the estuary by 25-200%, overwhelming climate-driven changes over the next decade. PMID- 26351689 TI - Broad and efficient control of major foodborne pathogenic strains of Escherichia coli by mixtures of plant-produced colicins. AB - Enterohemorrhagic Escherichia coli (EHEC) is one of the leading causes of bacterial enteric infections worldwide, causing ~100,000 illnesses, 3,000 hospitalizations, and 90 deaths annually in the United States alone. These illnesses have been linked to consumption of contaminated animal products and vegetables. Currently, other than thermal inactivation, there are no effective methods to eliminate pathogenic bacteria in food. Colicins are nonantibiotic antimicrobial proteins, produced by E. coli strains that kill or inhibit the growth of other E. coli strains. Several colicins are highly effective against key EHEC strains. Here we demonstrate very high levels of colicin expression (up to 3 g/kg of fresh biomass) in tobacco and edible plants (spinach and leafy beets) at costs that will allow commercialization. Among the colicins examined, plant-expressed colicin M had the broadest antimicrobial activity against EHEC and complemented the potency of other colicins. A mixture of colicin M and colicin E7 showed very high activity against all major EHEC strains, as defined by the US Department of Agriculture/Food and Drug Administration. Treatments with low (less than 10 mg colicins per L) concentrations reduced the pathogenic bacterial load in broth culture by 2 to over 6 logs depending on the strain. In experiments using meats spiked with E. coli O157:H7, colicins efficiently reduced the population of the pathogen by at least 2 logs. Plant-produced colicins could be effectively used for the broad control of pathogenic E. coli in both plant- and animal-based food products and, in the United States, colicins could be approved using the generally recognized as safe (GRAS) regulatory approval pathway. PMID- 26351690 TI - RNA transcription modulates phase transition-driven nuclear body assembly. AB - Nuclear bodies are RNA and protein-rich, membraneless organelles that play important roles in gene regulation. The largest and most well-known nuclear body is the nucleolus, an organelle whose primary function in ribosome biogenesis makes it key for cell growth and size homeostasis. The nucleolus and other nuclear bodies behave like liquid-phase droplets and appear to condense from the nucleoplasm by concentration-dependent phase separation. However, nucleoli actively consume chemical energy, and it is unclear how such nonequilibrium activity might impact classical liquid-liquid phase separation. Here, we combine in vivo and in vitro experiments with theory and simulation to characterize the assembly and disassembly dynamics of nucleoli in early Caenorhabditis elegans embryos. In addition to classical nucleoli that assemble at the transcriptionally active nucleolar organizing regions, we observe dozens of "extranucleolar droplets" (ENDs) that condense in the nucleoplasm in a transcription-independent manner. We show that growth of nucleoli and ENDs is consistent with a first-order phase transition in which late-stage coarsening dynamics are mediated by Brownian coalescence and, to a lesser degree, Ostwald ripening. By manipulating C. elegans cell size, we change nucleolar component concentration and confirm several key model predictions. Our results show that rRNA transcription and other nonequilibrium biological activity can modulate the effective thermodynamic parameters governing nucleolar and END assembly, but do not appear to fundamentally alter the passive phase separation mechanism. PMID- 26351691 TI - Candida albicans adapts to host copper during infection by swapping metal cofactors for superoxide dismutase. AB - Copper is both an essential nutrient and potentially toxic metal, and during infection the host can exploit Cu in the control of pathogen growth. Here we describe a clever adaptation to Cu taken by the human fungal pathogen Candida albicans. In laboratory cultures with abundant Cu, C. albicans expresses a Cu requiring form of superoxide dismutase (Sod1) in the cytosol; but when Cu levels decline, cells switch to an alternative Mn-requiring Sod3. This toggling between Cu- and Mn-SODs is controlled by the Cu-sensing regulator Mac1 and ensures that C. albicans maintains constant SOD activity for cytosolic antioxidant protection despite fluctuating Cu. This response to Cu is initiated during C. albicans invasion of the host where the yeast is exposed to wide variations in Cu. In a murine model of disseminated candidiasis, serum Cu was seen to progressively rise over the course of infection, but this heightened Cu response was not mirrored in host tissue. The kidney that serves as the major site of fungal infection showed an initial rise in Cu, followed by a decline in the metal. C. albicans adjusted its cytosolic SODs accordingly and expressed Cu-Sod1 at early stages of infection, followed by induction of Mn-Sod3 and increases in expression of CTR1 for Cu uptake. Together, these studies demonstrate that fungal infection triggers marked fluctuations in host Cu and C. albicans readily adapts by modulating Cu uptake and by exchanging metal cofactors for antioxidant SODs. PMID- 26351693 TI - Origami tubes assembled into stiff, yet reconfigurable structures and metamaterials. AB - Thin sheets have long been known to experience an increase in stiffness when they are bent, buckled, or assembled into smaller interlocking structures. We introduce a unique orientation for coupling rigidly foldable origami tubes in a "zipper" fashion that substantially increases the system stiffness and permits only one flexible deformation mode through which the structure can deploy. The flexible deployment of the tubular structures is permitted by localized bending of the origami along prescribed fold lines. All other deformation modes, such as global bending and twisting of the structural system, are substantially stiffer because the tubular assemblages are overconstrained and the thin sheets become engaged in tension and compression. The zipper-coupled tubes yield an unusually large eigenvalue bandgap that represents the unique difference in stiffness between deformation modes. Furthermore, we couple compatible origami tubes into a variety of cellular assemblages that can enhance mechanical characteristics and geometric versatility, leading to a potential design paradigm for structures and metamaterials that can be deployed, stiffened, and tuned. The enhanced mechanical properties, versatility, and adaptivity of these thin sheet systems can provide practical solutions of varying geometric scales in science and engineering. PMID- 26351692 TI - Caenorhabditis elegans ALG-1 antimorphic mutations uncover functions for Argonaute in microRNA guide strand selection and passenger strand disposal. AB - MicroRNAs are regulators of gene expression whose functions are critical for normal development and physiology. We have previously characterized mutations in a Caenorhabditis elegans microRNA-specific Argonaute ALG-1 (Argonaute-like gene) that are antimorphic [alg-1(anti)]. alg-1(anti) mutants have dramatically stronger microRNA-related phenotypes than animals with a complete loss of ALG-1. ALG-1(anti) miRISC (microRNA induced silencing complex) fails to undergo a functional transition from microRNA processing to target repression. To better understand this transition, we characterized the small RNA and protein populations associated with ALG-1(anti) complexes in vivo. We extensively characterized proteins associated with wild-type and mutant ALG-1 and found that the mutant ALG-1(anti) protein fails to interact with numerous miRISC cofactors, including proteins known to be necessary for target repression. In addition, alg 1(anti) mutants dramatically overaccumulated microRNA* (passenger) strands, and immunoprecipitated ALG-1(anti) complexes contained nonstoichiometric yields of mature microRNA and microRNA* strands, with some microRNA* strands present in the ALG-1(anti) Argonaute far in excess of the corresponding mature microRNAs. We show complex and microRNA-specific defects in microRNA strand selection and microRNA* strand disposal. For certain microRNAs (for example mir-58), microRNA guide strand selection by ALG-1(anti) appeared normal, but microRNA* strand release was inefficient. For other microRNAs (such as mir-2), both the microRNA and microRNA* strands were selected as guide by ALG-1(anti), indicating a defect in normal specificity of the strand choice. Our results suggest that wild-type ALG-1 complexes recognize structural features of particular microRNAs in the context of conducting the strand selection and microRNA* ejection steps of miRISC maturation. PMID- 26351696 TI - Emergence of electron coherence and two-color all-optical switching in MoS2 based on spatial self-phase modulation. AB - Generating electron coherence in quantum materials is essential in optimal control of many-body interactions and correlations. In a multidomain system this signifies nonlocal coherence and emergence of collective phenomena, particularly in layered 2D quantum materials possessing novel electronic structures and high carrier mobilities. Here we report nonlocal ac electron coherence induced in dispersed MoS2 flake domains, using coherent spatial self-phase modulation (SSPM). The gap-dependent nonlinear dielectric susceptibility chi(3) measured is surprisingly large, where direct interband transition and two-photon SSPM are responsible for excitations above and below the bandgap, respectively. A wind chime model is proposed to account for the emergence of the ac electron coherence. Furthermore, all-optical switching is achieved based on SSPM, especially with two-color intraband coherence, demonstrating that electron coherence generation is a ubiquitous property of layered quantum materials. PMID- 26351695 TI - Biochemical isolation of Argonaute protein complexes by Ago-APP. AB - During microRNA (miRNA)-guided gene silencing, Argonaute (Ago) proteins interact with a member of the TNRC6/GW protein family. Here we used a short GW protein derived peptide fused to GST and demonstrate that it binds to Ago proteins with high affinity. This allows for the simultaneous isolation of all Ago protein complexes expressed in diverse species to identify associated proteins, small RNAs, or target mRNAs. We refer to our method as "Ago protein Affinity Purification by Peptides" (Ago-APP). Furthermore, expression of this peptide competes for endogenous TNRC6 proteins, leading to global inhibition of miRNA function in mammalian cells. PMID- 26351694 TI - Nanoscale patterning of STIM1 and Orai1 during store-operated Ca2+ entry. AB - Stromal interacting molecule (STIM) and Orai proteins constitute the core machinery of store-operated calcium entry. We used transmission and freeze fracture electron microscopy to visualize STIM1 and Orai1 at endoplasmic reticulum (ER)-plasma membrane (PM) junctions in HEK 293 cells. Compared with control cells, thin sections of STIM1-transfected cells possessed far more ER elements, which took the form of complex stackable cisternae and labyrinthine structures adjoining the PM at junctional couplings (JCs). JC formation required STIM1 expression but not store depletion, induced here by thapsigargin (TG). Extended molecules, indicative of STIM1, decorated the cytoplasmic surface of ER, bridged a 12-nm ER-PM gap, and showed clear rearrangement into small clusters following TG treatment. Freeze-fracture replicas of the PM of Orai1-transfected cells showed extensive domains packed with characteristic "particles"; TG treatment led to aggregation of these particles into sharply delimited "puncta" positioned upon raised membrane subdomains. The size and spacing of Orai1 channels were consistent with the Orai crystal structure, and stoichiometry was unchanged by store depletion, coexpression with STIM1, or an Orai1 mutation (L273D) affecting STIM1 association. Although the arrangement of Orai1 channels in puncta was substantially unstructured, a portion of channels were spaced at ~15 nm. Monte Carlo analysis supported a nonrandom distribution for a portion of channels spaced at ~15 nm. These images offer dramatic, direct views of STIM1 aggregation and Orai1 clustering in store-depleted cells and provide evidence for the interaction of a single Orai1 channel with small clusters of STIM1 molecules. PMID- 26351697 TI - Evidence for superconductivity in Li-decorated monolayer graphene. AB - Monolayer graphene exhibits many spectacular electronic properties, with superconductivity being arguably the most notable exception. It was theoretically proposed that superconductivity might be induced by enhancing the electron-phonon coupling through the decoration of graphene with an alkali adatom superlattice [Profeta G, Calandra M, Mauri F (2012) Nat Phys 8(2):131-134]. Although experiments have shown an adatom-induced enhancement of the electron-phonon coupling, superconductivity has never been observed. Using angle-resolved photoemission spectroscopy (ARPES), we show that lithium deposited on graphene at low temperature strongly modifies the phonon density of states, leading to an enhancement of the electron-phonon coupling of up to lambda ? 0.58. On part of the graphene-derived pi*-band Fermi surface, we then observe the opening of a Delta ? 0.9-meV temperature-dependent pairing gap. This result suggests for the first time, to our knowledge, that Li-decorated monolayer graphene is indeed superconducting, with Tc ? 5.9 K. PMID- 26351701 TI - Systemic in vivo delivery of siRNA to tumours using combination of polyethyleneimine and transferrin-polyethyleneimine conjugates. AB - Materials for delivery of oligonucleotides need to be simple to produce yet effective in vivo to be considered for clinical applications. Formulations of biomaterials based on combinations of existing demonstrated polymeric gene carriers with targeted derivatives are potential candidates for rapid translation but have not been fully explored for siRNA applications. Here we investigated formulations based on derivatised PEI for delivery of siRNA to gastrointestinal cancer cells. siRNA was complexed with linear PEI alone or with a mixture of linear PEI and transferrin-conjugated branched PEI (TfPEI), and knockdown of reporter genes was investigated. Overall, the in vitro use of complexes containing TfPEI resulted in up to 93% knockdown at 72 h post-transfection. Sustained knockdown was also achieved in a bioluminescent xenograft model. When complexes were delivered intratumorally, a 43% reduction in luminescence was achieved in the treated group compared with the control group 48 h after treatment. For systemic administration, only the intraperitoneal route, and not the intravenous route was effective, with 49% knockdown achieved at 72 h and sustained up to 144 h (44%) after a single administration of TfPEI-complexed siRNA. No toxicity or induction of the interferon response was observed. These findings demonstrate that simple formulations of transferrin-conjugated PEI with a 'parent' polymer such as linear PEI have potential as a method for therapeutic delivery of siRNA when administered either intratumorally or systemically. PMID- 26351702 TI - Na2MoO(2-delta)F(4+delta)--a perovskite with a unique combination of atomic orderings and octahedral tilts. AB - Na2MoO2-deltaF4+delta (delta ~ 0.08) displays a unique variant of the perovskite structure, with simultaneous (Na,vacancy) ordering on the A-site, (Na,Mo) ordering on the B-site, (O,F) ordering on the anion site and an unusual NaNbO3 like octahedral tilt system. PMID- 26351699 TI - Peptide dimer structure in an Abeta(1-42) fibril visualized with cryo-EM. AB - Alzheimer's disease (AD) is a fatal neurodegenerative disorder in humans and the main cause of dementia in aging societies. The disease is characterized by the aberrant formation of beta-amyloid (Abeta) peptide oligomers and fibrils. These structures may damage the brain and give rise to cerebral amyloid angiopathy, neuronal dysfunction, and cellular toxicity. Although the connection between AD and Abeta fibrillation is extensively documented, much is still unknown about the formation of these Abeta aggregates and their structures at the molecular level. Here, we combined electron cryomicroscopy, 3D reconstruction, and integrative structural modeling methods to determine the molecular architecture of a fibril formed by Abeta(1-42), a particularly pathogenic variant of Abeta peptide. Our model reveals that the individual layers of the Abeta fibril are formed by peptide dimers with face-to-face packing. The two peptides forming the dimer possess identical tilde-shaped conformations and interact with each other by packing of their hydrophobic C-terminal beta-strands. The peptide C termini are located close to the main fibril axis, where they produce a hydrophobic core and are surrounded by the structurally more flexible and charged segments of the peptide N termini. The observed molecular architecture is compatible with the general chemical properties of Abeta peptide and provides a structural basis for various biological observations that illuminate the molecular underpinnings of AD. Moreover, the structure provides direct evidence for a steric zipper within a fibril formed by full-length Abeta peptide. PMID- 26351703 TI - Role of entropic effects in controlling the polymorphism in formate ABX3 metal organic frameworks. AB - Polymorphism in formate-based dense metal-organic frameworks with the general formula ABX3 is predicted by quantum chemical calculations and confirmed experimentally. In particular [NH3NH2]Zn(HCOO)3 crystallizes in two different polymorphs, a perovskite-like framework and a chiral structure with hexagonal channels. A detailed thermodynamic analysis reveals that both structures are very close in free energy and that entropy driven effects are responsible for stabilizing the channel structure. PMID- 26351704 TI - Spectral properties and isomerisation path of retinal in C1C2 channelrhodopsin. AB - Structure and excited state isomerisation pathway of retinal in the channelrhodopsin chimera C1C2 have been investigated with combined quantum mechanical/molecular mechanical (QM/MM) techniques, applying CD-MS-CASPT2//CASSCF and DFT-MRCI quantum methods. The absorbing S1 state is of (1)Bu-like character, and the second excited S2 state is dominated by HOMO-LUMO double excitation with small oscillator strength. Upon photoexcitation and torsion along the reactive C13[double bond, length as m-dash]C14 double bond we observe bond length equalisation and a two-path deactivation mechanism in positive and negative torsion directions. The computed path is barrierless in positive direction while a small barrier exists for the opposite side. Comparative protonation studies suggest a charged glutamate E162 residue, with computed resonance Raman data in valuable agreement with experimental channelrhodopsin-2 data. The two negatively charged counter-ions and a positive lysine residue close to the retinal Schiff base terminus have the largest influence on the chromophore absorption wavelength. PMID- 26351705 TI - Anomalous system-size dependence of electrolytic cells with an electrified oil water interface. AB - Manipulation of the charge of the dielectric interface between two bulk liquids not only enables the adjustment of the interfacial tension but also controls the storage capacity of ions in the ionic double layers adjacent to each side of the interface. However, adjusting this interfacial charge by static external electric fields is difficult since the external electric fields are readily screened by ionic double layers that form in the vicinity of the external electrodes. This leaves the liquid-liquid interface, which is at a macroscopic distance from the electrodes, unaffected. In this study we show theoretically, in agreement with recent experiments, that control over this surface charge at the liquid-liquid interface is nonetheless possible for macroscopically large but finite closed systems in equilibrium, even when the distance between the electrode and interface is orders of magnitude larger than the Debye screening lengths of the two liquids. We identify a crossover system-size below which the interface and the electrodes are effectively coupled. Our calculations of the interfacial tension for various electrode potentials are in good agreement with recent experimental data. PMID- 26351698 TI - MINCR is a MYC-induced lncRNA able to modulate MYC's transcriptional network in Burkitt lymphoma cells. AB - Despite the established role of the transcription factor MYC in cancer, little is known about the impact of a new class of transcriptional regulators, the long noncoding RNAs (lncRNAs), on MYC ability to influence the cellular transcriptome. Here, we have intersected RNA-sequencing data from two MYC-inducible cell lines and a cohort of 91 B-cell lymphomas with or without genetic variants resulting in MYC overexpression. We identified 13 lncRNAs differentially expressed in IG-MYC positive Burkitt lymphoma and regulated in the same direction by MYC in the model cell lines. Among them, we focused on a lncRNA that we named MYC-induced long noncoding RNA (MINCR), showing a strong correlation with MYC expression in MYC positive lymphomas. To understand its cellular role, we performed RNAi and found that MINCR knockdown is associated with an impairment in cell cycle progression. Differential gene expression analysis after RNAi showed a significant enrichment of cell cycle genes among the genes down-regulated after MINCR knockdown. Interestingly, these genes are enriched in MYC binding sites in their promoters, suggesting that MINCR acts as a modulator of the MYC transcriptional program. Accordingly, MINCR knockdown was associated with a reduction in MYC binding to the promoters of selected cell cycle genes. Finally, we show that down-regulation of Aurora kinases A and B and chromatin licensing and DNA replication factor 1 may explain the reduction in cellular proliferation observed on MINCR knockdown. We, therefore, suggest that MINCR is a newly identified player in the MYC transcriptional network able to control the expression of cell cycle genes. PMID- 26351706 TI - Fractional photo-current dependence of graphene quantum dots prepared from carbon nanotubes. AB - We report on the photo-conductivity studies of chemically synthesized graphene quantum dots (GQDs) of average size 12 nm obtained by the oxidative acid treatment of MWCNTs. The dependence of photocurrent Iph (Iph = Iill - Idark) on the laser intensity P under a wide range of laser intensities (5 mW <= P <= 60 mW) shows a fractional power dependence of Iph on light intensity. The temperature dependence (300 K < T < 50 K) of Iph observed in thin films of these GQDs indicates that in the higher temperature region (T > ~100 K), as the temperature increases, the number of thermally generated carriers increase resulting in increased Iph. At sufficiently low temperatures (T <= 100 K), a constant Iph is observed, indicating a constant photo-carrier density. Such a behavior is typically observed in many photoactive disordered semiconductors, which are often used in a variety of applications. We believe that the investigations presented here will enhance our understanding of the photocurrent generation phenomenon in chemically obtained GQDs. PMID- 26351707 TI - Unexpected Spin-Crossover and a Low-Pressure Phase Change in an Iron(II)/Dipyrazolylpyridine Complex Exhibiting a High-Spin Jahn- Teller Distortion. AB - The synthesis of 4-methyl-2,6-di(pyrazol-1-yl)pyridine (L) and four salts of [FeL2]X2 (X- = BF(4)(-), 1; X- = ClO(4)(-), 2; X- = PF(6)(-), 3; X- = CF3SO(3)( ), 4) are reported. Powder samples of 1 and 2 both exhibit abrupt, hysteretic spin-state transitions on cooling, with T(1/2)? = 204 and T(1/2)? = 209 K (1), and T(1/2)? = 175 and T(1/2)? = 193 K (2). The 18 K thermal hysteresis loop for 2 is unusually wide for a complex of this type. Single crystal structures of 2 show it to exhibit a Jahn-Teller-distorted six-coordinate geometry in its high-spin state, which would normally inhibit spin-crossover. Bulk samples of 1 and 2 are isostructural by X-ray powder diffraction, and undergo a crystallographic phase change during their spin-transitions. At temperatures below T(1/2), exposing both compounds to 10(-5) Torr pressure inside the powder diffractometer causes a reversible transformation back to the high-temperature crystal phase. Consideration of thermodynamic data implies this cannot be accompanied by a low > high spin-state change, however. Both compounds also exhibit the LIESST effect, with 2 exhibiting an unusually high T(LIESST) of 112 K. The salts 3 and 4 are respectively high-spin and low-spin between 3 and 300 K, with crystalline 3 exhibiting a more pronounced version of the same Jahn-Teller distortion. PMID- 26351708 TI - Holes in the brain: Virchow-Robin spaces (giant perivascular spaces). PMID- 26351709 TI - Copper Lanthanide Phosphonate Cages: Highly Symmetric {Cu3Ln9P6} and {Cu6Ln6P6} Clusters with C3v and D3h Symmetry. AB - Two families of copper lanthanide phosphonate clusters have been obtained through reaction of [Cu2(O2CtBu)4(HO2CtBu)2] and either Ln(NO3)3.nH2O or [Ln2(O2CtBu)6(HO2CtBu)6] and tert-butylphosphonic acid or an amino-functionalized phosphonic acid. The clusters, with general formula [Cu(MeCN)4][Cu3Ln9(MU3 OH)7(O3PtBu)6(O2CtBu)15] and [Cu6Ln6(MU3-OH)6(O3PC(NH2)Me2)6(O2CtBu)12], were structurally characterized through single crystal X-ray diffraction and possess highly symmetric metal cores with approximately C3v and D3h point symmetry, respectively. We have investigated the possible application of the isotropic analogues in magnetic cooling, where we were able to observe that up to around 70% of the theoretical magnetic entropy change is obtained. Simulation of the magnetic data shows antiferromagnetic coupling between the spin centers, which explains the magnetic entropy value observed. PMID- 26351710 TI - Highly Selective and Sensitive Luminescence Turn-On-Based Sensing of Al3+ Ions in Aqueous Medium Using a MOF with Free Functional Sites. AB - A new metal-organic framework [Co(OBA)(DATZ)0.5(H2O)] {OBA = 4,4'-oxybis(benzoic acid) and DATZ = 3,5-diamino-1,2,4-triazole}, 1, was synthesized by hydrothermal reaction. Single-crystal X-ray data of 1 confirmed two-dimensional rhombus grid network topology with a free nitrogen site of triazole ring and two amine groups of each DATZ. Photoluminescence study of 1 in aqueous medium shows blue emission at 407 nm upon excitation at 283 nm. This emissive property was used for the sensing of Al3+ ions in aqueous medium through very high luminescence turn-on (6.3-fold) along with the blue shifting (~24 nm) of the emission peak. However, luminescence studies in the presence of other common metal ions such as Mg2+, Zn2+, Ni2+, Co2+, Mn2+, K+, Na+, Ca2+, Cd2+, Hg2+, Cu2+, Fe2+, Fe3+, and Cr3+ in aqueous medium shows luminescence quenching in varying extent. Interestingly, the luminescence turn-on-based selectivity of Al3+ ions in aqueous medium was achieved even in the presence of the highest quenchable metal ion, Fe3+. Furthermore, very high sensitivity was observed in the case of Al3+ ions with a limit of detection of Al3+ of 57.5 ppb, which is significantly lower than the higher limit of U.S. Environmental Protection Agency recommendation of Al3+ ion for drinking water (200 ppb). PMID- 26351711 TI - A life devoted to aquatic ecology: a tribute to Otto Kinne. PMID- 26351712 TI - Author's Reply. PMID- 26351713 TI - Author's Reply. PMID- 26351714 TI - Author's Reply. PMID- 26351715 TI - RESPONSE: Placing Value in Peer Mentorship. PMID- 26351716 TI - India-small progress in health care, decline in rural services. PMID- 26351720 TI - Investigating "Microbial Dark Matter". PMID- 26351721 TI - Oral Healthcare 2015; Where the Money's Going... PMID- 26351722 TI - Jawbone Printed on Titanium Implanted in Wounded Man. PMID- 26351723 TI - Secondhand Smoke: A New Risk Factor for Caries in Children? PMID- 26351724 TI - Educators and Clinicians Create New Assessment Tool to Improve Oral-Systemic Health. PMID- 26351725 TI - U.S. Environmental Protection Agency Issues New Radiation Usage Guidelines. PMID- 26351726 TI - Suffering From Malocclusion? Blame Farmers.... PMID- 26351727 TI - D-fense! Advocating the Need for the Vitamin During the Winter Months. PMID- 26351728 TI - Benzimidazole Derivatives as Potent JAK1-Selective Inhibitors. AB - The Janus kinase (JAK) family comprises four members (JAK1, JAK2, JAK3, and Tyk2) that play a key role in mediating cytokine receptor signaling. JAK inhibition thus modulates cytokine-mediated effects. In particular, selective inhibition of JAK1 or JAK3 may provide an efficient therapeutic agent for the treatment of inflammatory diseases, with minimized side effects. In this study, as part of our continued efforts to develop a selective JAK1 inhibitor, a series of 1,2 disubstituted benzimidazole-5-carboxamide derivatives was prepared and their inhibitory activities against all four JAK isozymes were evaluated. A clear structure-activity relationship was observed with respect to JAK1 selectivity; this highlighted the importance of hydrogen bond donors at both N(1) and R2 positions located within a specific distance from the benzimidazole core. One of the synthesized compounds, 1-(2-aminoethyl)-2-(piperidin-4-yl)-1H benzo[d]imidazole-5-carboxamide (5c), showed remarkable JAK1 selectivity (63-fold vs JAK2, 25-fold vs JAK3, and 74-fold vs Tyk2). Molecular docking revealed that the 2-aminoethyl and piperidin-4-yl substituents of 5c function as probes to differentiate the ATP-binding site of JAK1 from that of JAK2, resulting in preferential JAK1 binding. A kinase panel assay confirmed the JAK1 selectivity of 5c, which showed no appreciable inhibitory activity against 26 other protein kinases at 10 MUM. PMID- 26351729 TI - Living Composites of Electrospun Yeast Cells for Bioremediation and Ethanol Production. AB - The preparation of composites of living functional cells and polymers is a major challenge. We have fabricated such "living composites" by preparation of polymeric microtubes that entrap yeast cells. Our approach was the process of coaxial electrospinning in which a core containing the yeast was "spun" within a shell of nonbiodegradable polymer. We utilized the yeast Candida tropicalis, which was isolated from olive water waste. It is particularly useful since it degrades phenol and other natural polyphenols, and it is capable of accumulating ethanol. The electrospun yeast cells showed significant activity of bioremediation of phenol and produced ethanol, and, in addition, the metabolic processes remained active for a prolonged period. Comparison of electrospun cells to planktonic cells showed decreased cell activity; however, the olive water waste after treatment by the yeast was no longer toxic for Escherichia coli, suggesting that detoxification and prolonged viability and activity may outweigh the reduction of efficiency. PMID- 26351730 TI - Detection of a mosaic PIK3CA mutation in dental DNA from a child with megalencephaly capillary malformation syndrome. AB - The megalencephaly capillary malformation syndrome (MCAP, OMIM 602501) is known to be associated with mosaic mutations in PIK3CA occurring during embryogenesis. Standard sequencing technologies are relatively poor at indentifying sequence changes that only affect a small percentage of cells, and the mutations are frequently not identified in lymphocyte DNA, with biopsies of the affected tissues often being required to detect mosaic mutations. Such invasive procedures are not always acceptable to parents. We describe the case of a patient in whom we were able to confirm a causative PIK3CA mutation, first found thorugh next generation sequencing, in several tissue types including a secondary tooth. As part of this work, we were also able to begin validating dental tissue for potential use in genetic testing, as we achieved excellent DNA yields with minimal effort, even from deciduous teeth shed some years earlier. PMID- 26351731 TI - Area-Selective Atomic Layer Deposition: Conformal Coating, Subnanometer Thickness Control, and Smart Positioning. AB - Transistors have already been made three-dimensional (3D), with device channels (i.e., fins in trigate field-effect transistor (FinFET) technology) that are taller, thinner, and closer together in order to enhance device performance and lower active power consumption. As device scaling continues, these transistors will require more advanced, fabrication-enabling technologies for the conformal deposition of high-kappa dielectric layers on their 3D channels with accurate position alignment and thickness control down to the subnanometer scale. Among many competing techniques, area-selective atomic layer deposition (AS-ALD) is a promising method that is well suited to the requirements without the use of complicated, complementary metal-oxide semiconductor (CMOS)-incompatible processes. However, further progress is limited by poor area selectivity for thicker films formed via a higher number of ALD cycles as well as the prolonged processing time. In this issue of ACS Nano, Professor Stacy Bent and her research group demonstrate a straightforward self-correcting ALD approach, combining selective deposition with a postprocess mild chemical etching, which enables selective deposition of dielectric films with thicknesses and processing times at least 10 times larger and 48 times shorter, respectively, than those obtained by conventional AS-ALD processes. These advances present an important technological breakthrough that may drive the AS-ALD technique a step closer toward industrial applications in electronics, catalysis, and photonics, etc. where more efficient device fabrication processes are needed. PMID- 26351733 TI - Pyrolysis Pathways of the Furanic Ether 2-Methoxyfuran. AB - Substituted furans, including furanic ethers, derived from nonedible biomass have been proposed as second-generation biofuels. In order to use these molecules as fuels, it is important to understand how they break apart thermally. In this work, a series of experiments were conducted to study the unimolecular and low pressure bimolecular decomposition mechanisms of the smallest furanic ether, 2 methoxyfuran. Electronic structure (CBS-QB3) calculations indicate this substituted furan has an unusually weak O-CH3 bond, approximately 190 kJ mol(-1) (45 kcal mol(-1)); thus, the primary decomposition pathway is through bond scission resulting in CH3 and 2-furanyloxy (O-C4H3O) radicals. Final products from the ring opening of the furanyloxy radical include 2 CO, HC=CH, and H. The decomposition of methoxyfuran is studied over a range of concentrations (0.0025 0.1%) in helium or argon in a heated silicon carbide (SiC) microtubular flow reactor (0.66-1 mm i.d., 2.5-3.5 cm long) with reactor wall temperatures from 300 to 1300 K. Inlet pressures to the reactor are 150-1500 Torr, and the gas mixture emerges as a skimmed molecular beam at a pressure of approximately 10 MUTorr. Products formed at early pyrolysis times (100 MUs) are detected by 118.2 nm (10.487 eV) photoionization mass spectrometry (PIMS), tunable synchrotron VUV PIMS, and matrix infrared absorption spectroscopy. Secondary products resulting from H or CH3 addition to the parent and reaction with 2-furanyloxy were also observed and include CH2?CH-CHO, CH3-CH?CH-CHO, CH3-CO-CH?CH2, and furanones; under the conditions in the reactor, we estimate these reactions contribute to at most 1-3% of total methoxyfuran decomposition. This work also includes observation and characterization of an allylic lactone radical, 2-furanyloxy (O C4H3O), with the assignment of several intense vibrational bands in an Ar matrix, an estimate of the ionization threshold, and photoionization efficiency. A pressure-dependent kinetic mechanism is also developed to model the decomposition behavior of methoxyfuran and provide pathways for the minor bimolecular reaction channels that are observed experimentally. PMID- 26351732 TI - Tracking the Flow of Resources in Electronic Waste - The Case of End-of-Life Computer Hard Disk Drives. AB - Recovery of resources, in particular, metals, from waste flows is widely seen as a prioritized option to reduce their potential supply constraints in the future. The current waste electrical and electronic equipment (WEEE) treatment system is more focused on bulk metals, where the recycling rate of specialty metals, such as rare earths, is negligible compared to their increasing use in modern products, such as electronics. This study investigates the challenges in recovering these resources in the existing WEEE treatment system. It is illustrated by following the material flows of resources in a conventional WEEE treatment plant in Denmark. Computer hard disk drives (HDDs) containing neodymium iron-boron (NdFeB) magnets were selected as the case product for this experiment. The resulting output fractions were tracked until their final treatment in order to estimate the recovery potential of rare earth elements (REEs) and other resources contained in HDDs. The results further show that out of the 244 kg of HDDs treated, 212 kg comprising mainly of aluminum and steel can be finally recovered from the metallurgic process. The results further demonstrate the complete loss of REEs in the existing shredding-based WEEE treatment processes. Dismantling and separate processing of NdFeB magnets from their end-use products can be a more preferred option over shredding. However, it remains a technological and logistic challenge for the existing system. PMID- 26351734 TI - Molecular Dynamics Simulations of a Powder Model of the Intrinsically Disordered Protein Tau. AB - The tau protein, whose aggregates are involved in Alzheimer's disease, is an intrinsically disordered protein (IDP) that regulates microtubule activity in neurons. An IDP lacks a single, well-defined structure and, rather, constantly exchanges among multiple conformations. In order to study IDP dynamics, the combination of experimental techniques, such as neutron scattering, and computational techniques, such as molecular dynamics (MD) simulations, is a powerful approach. Amorphous hydrated powder samples have been very useful for studying protein internal dynamics experimentally, e.g., using neutron scattering. Thus, there is demand for realistic in silico models of hydrated protein powders. Here we present an MD simulation analysis of a powder hydrated at 0.4 g water/g protein of the IDP tau in the temperature range 20-300 K. By comparing with neutron scattering data, we identify the protein-water interface as the predominant feature determining IDP dynamics. The so-called protein dynamical transition is shown to be attenuated, but not suppressed, in the parts of the protein that are not exposed to the solvent. In addition, we find similarities in the mean-squared displacements of the core of a globular protein and "dry" clusters formed by the IDP in hydrated powders. Thus, the ps to ns dynamics of proteins in hydrated powders originate mainly from those residues in contact with solvent. We propose that by measuring the dynamics of protein assemblies, such as aggregates, one might assess qualitatively their state of hydration. PMID- 26351735 TI - A Longitudinal Study of Resting Heart Rate and Violent Criminality in More Than 700 000 Men. AB - IMPORTANCE: Low resting heart rate is a well-replicated physiological correlate of aggressive and antisocial behavior in children and adolescents, but whether low resting heart rate increases the risk of violence and other antisocial and risk-taking behaviors in adulthood has not been studied in representative samples. OBJECTIVE: To study the predictive association of resting heart rate with violent and nonviolent criminality and with fatal and nonfatal injuries owing to assaults and unintentional injuries in the population. DESIGN, SETTING, AND PARTICIPANTS: We conducted a study of data from several Swedish national registers on 710 264 Swedish men in the general population born from 1958 to 1991, with a follow-up of up to 35.7 years. Outcome data were available and analyzed from January 1, 1973, through December 31, 2009. Resting heart rate was measured together with blood pressure at mandatory military conscription testing at a mean (SD) age of 18.2 (0.5) years. MAIN OUTCOMES AND MEASURES: Violent and nonviolent criminal convictions and medical treatments or deaths owing to assaults and unintentional injuries. RESULTS: In models adjusted for physical, cardiovascular, psychiatric, cognitive, and socioeconomic covariates, compared with 139 511 men in the highest quintile of the distribution of resting heart rate (>=83 beats/min), 132 595 men with the lowest quintile (heart rate, <=60 beats/min) had a 39% (95% CI, 35%-44%) higher hazard of being convicted of violent crimes and a 25% (95% CI, 23%-28%) higher hazard of being convicted of nonviolent crimes. The corresponding hazard was 39% higher for assault injuries (95% CI, 33%-46%) and for unintentional injuries (95% CI, 38%-41%). Further adjustment for cardiorespiratory fitness in a subset of 572 610 men with data from an exercise test did not reduce the associations. Similar associations were found between low systolic blood pressure and violent and nonviolent criminality and for assault injuries when systolic blood pressure was studied instead of resting heart rate in more than 1 million men. CONCLUSIONS AND RELEVANCE: Among men, low resting heart rate in late adolescence was associated with an increased risk for violent criminality, nonviolent criminality, exposure to assault, and unintentional injury in adulthood. Most of these results were replicated with low systolic blood pressure. Resting heart rate and other autonomic measures merit further study in the development and prevention of violence and antisocial behavior. PMID- 26351736 TI - Reducing adsorption to improve recovery and in vivo detection of neuropeptides by microdialysis with LC-MS. AB - Neuropeptides are an important class of neurochemicals; however, measuring their concentration in vivo by using microdialysis sampling is challenging due to their low concentration and the small samples generated. Capillary liquid chromatography with mass spectrometry (cLC-MS) can yield attomole limits of detection (LOD); however, low recovery and loss of sample to adsorptive surfaces can still hinder detection of neuropeptides. We have evaluated recovery during sampling and transfer to the cLC column for a selection of 10 neuropeptides. Adding acetonitrile to sample eliminated carryover and improved LOD by 1.4- to 60 fold. The amount of acetonitrile required was found to have an optimal value that correlated with peptide molecular weight and retention time on a reversed phase LC column. Treating AN69 dialysis membrane, which bears negative charge due to incorporated sulfonate groups, with polyethylenimine (PEI) improved recovery by 1.2- to 80-fold. The effect appeared to be due to reducing electrostatic interaction between peptides and the microdialysis probe because modification increased recovery only for peptides that carried net positive charge. The combined effects improved LOD of the entire method by 1.3- to 800-fold for the different peptides. We conclude that peptides with both charged and hydrophobic regions require combined strategies to prevent adsorption and yield the best possible detection. The method was demonstrated by determining orexin A, orexin B, and a novel isoform of rat beta-endorphin in the arcuate nucleus. Dialysate concentrations were below 10 pM for these peptides. A standard addition study on dialysates revealed that while some peptides can be accurately quantified, some are affected by the matrix. PMID- 26351738 TI - Pore formation by actinoporins, cytolysins from sea anemones. AB - Actinoporins (APs) from sea anemones are ~20 kDa pore forming toxins with a beta sandwich structure flanked by two alpha-helices. The molecular mechanism of APs pore formation is composed of several well-defined steps. APs bind to membrane by interfacial binding site composed of several aromatic amino acid residues that allow binding to phosphatidylcholine and specific recognition of sphingomyelin. Subsequently, the N-terminal alpha-helix from the beta-sandwich has to be inserted into the lipid/water interphase in order to form a functional pore. Functional studies and single molecule imaging revealed that only several monomers, 3-4, oligomerise to form a functional pore. In this model the alpha helices and surrounding lipid molecules build toroidal pore. In agreement, AP pores are transient and electrically heterogeneous. On the contrary, crystallized oligomers of actinoporin fragaceatoxin C were found to be composed of eight monomers with no lipids present between the adjacent alpha-helices. This article is part of a Special Issue entitled: Pore-Forming Toxins edited by Maur Dalla Serra and Franco Gambale. PMID- 26351740 TI - Robot-assisted retroperitoneal lymph node dissection in testicular cancer. AB - Robotic surgical techniques are now being applied in the setting of retroperitoneal lymphadenectomy (RPLND) for testicular cancer. While laparoscopic RPLND has not been widely accepted, reports of robot assisted RPLND (RARPLND) are emerging. This manuscript will review the application of RPLND for testicular cancer, evolution of minimally invasive techniques, the controversies, and current status of RARPLND. PMID- 26351741 TI - The effect of hypoxia on the formation of mouse incisor enamel. AB - OBJECTIVE: The permanently growing mouse incisors exhibit all stages of tooth development along their inciso-apical axis at any time. Any disturbance or injury of the ameloblasts during enamel formation or maturation may result in permanent defects in the finished enamel since the enamel does not undergo repair or remodeling after formation. In order to increase our understanding of how hypoxia affects enamel formation, we induced severe acute hypoxia in adult mice and observed its effects on the enamel in incisors. DESIGN: Incisors from hypoxic mice were obtained 5 and 49 days after the hypoxic insult. Hypoxic and control incisors were dissected out and observed by scanning electron microscopy (SEM). Incisors were subsequently ground longitudinally or transversely, etched, and observed again by SEM. The nature and position of defects were considered in relation to the configuration and dynamics of the incisors. RESULTS: The effect of hypoxia varied considerably, among mice, among incisors, and among ameloblasts. Affected enamel showed hypoplasia with hypomineralization or hypomineralization without hypoplasia. Vascular endothelial growth factor (VEGF) showed considerably stronger labeling in hypoxic compared to control ameloblasts. CONCLUSIONS: The present study demonstrates quantitative and qualitative defects in the enamel reflecting the vulnerability of ameloblasts toward severe acute hypoxia in mouse incisors. PMID- 26351742 TI - MiR-143 and miR-135 inhibitors treatment induces skeletal myogenic differentiation of human adult dental pulp stem cells. AB - OBJECTIVE: Dental pulp stem cells (DPSCs) possess pluripotent properties that allow them to differentiate into multiple cell lineages, which can be potentially used in tissue regeneration. The aim of this in vitro study is to explore the effect of miRNAs on the myogenic differentiation of human adult DPSCs and seek for some potential biological factors for stable and feasible application in DPSC myogenic differentiation. METHODS: Human adult DPSCs were isolated from normal impacted third molars were treated with 5-Aza-2'-deoxycytidine to induce to myogenic differentiation in vitro. During this process the levels of myomiRNAs and myogenic marker genes were detected by real-time qPCR and Western blotting. Then antisense oligonucleotides of miR-143 and miR-135 were transfected into DPSCs to explore their effects on myogenic differentiation. Gene expression detection and MyHC immunofluorescence microscopy analysis were applied to characterize the myogenic differentiation of DPSCs. RESULTS: Expression of miR 135 and miR-143 was markedly decreased in myoblast DPSCs induced by 5-Aza. Part of the DPSCs treated with miR-135 or miR-143 inhibitors showed apparent myocytic properties and eventually fused to form myotubes. Co-transfection of miR-135 and miR-143 inhibitors impelled half of DPSCs to form myotubes. CONCLUSION: MiR-135 and miR-143 inhibitors could induce myogenic differentiation of DPSCs. Our findings indicated that miRNAs could exert a decisive function in induction of myogenic differentiation of DPSCs. PMID- 26351737 TI - Nicotinic acetylcholine receptors: upregulation, age-related effects and associations with drug use. AB - Nicotinic acetylcholine receptors are ligand-gated ion channels that exogenously bind nicotine. Nicotine produces rewarding effects by interacting with these receptors in the brain's reward system. Unlike other receptors, chronic stimulation by an agonist induces an upregulation of receptor number that is not due to increased gene expression in adults; while upregulation also occurs during development and adolescence there have been some opposing findings regarding a change in corresponding gene expression. These receptors have also been well studied with regard to human genetic associations and, based on evidence suggesting shared genetic liabilities between substance use disorders, numerous studies have pointed to a role for this system in comorbid drug use. This review will focus on upregulation of these receptors in adulthood, adolescence and development, as well as the findings from human genetic association studies which point to different roles for these receptors in risk for initiation and continuation of drug use. PMID- 26351743 TI - Risk factors related to sleep bruxism in children: A systematic literature review. AB - OBJECTIVE: The aim of this article was to systematically review the literature to identify papers dealing with risk factors associated with sleep bruxism (SB) in children. DESIGN: A systematic search was carried out based on the following databases: PubMed, Embase, Scopus, Cochrane Oral Health Group's Trial Register and Cochrane Register of Controlled Trials, Web of Science, LILACs, SciELO. Studies investigating risk factors related to SB after multiple regression analysis and bruxism symptoms assessed with clinical diagnosis or specific questionnaires were searched. Six out of the 4546 initially identified studies were selected. This review was conducted according to the guidelines from the Cochrane Handbook for Systematic Reviews of Interventions, with reporting in agreement to the Preferred Reporting Items for Systematic Reviews and Meta analyses guidelines. RESULTS: Among the six analyzed articles, one randomized clinical trial (RCT) suggested the increase of SB in heavily exposed patients to second hand smoke (SHS) (OR=4.5, CI=2.2-9.4), two cross-sectional studies suggested neuroticism as determinant factor for the development of sleep bruxism (OR=1.9, CI=1.3-2.6), among children and three case-control studies suggested that children with sleep disturbances were more likely to have SB (OR=3.3, CI=1.6 6.6). Parafunctional behaviours (OR=2.3, CI=1.2-4.3) had a moderate association. CONCLUSIONS: SHS and sleep disturbances presented the strongest association with SB. The most recurrent source of bias was the lack of blinding procedures. Furthermore, the use of reliable SB diagnostic procedures should be recommended to increase the quality of future studies. The evidence emerged from the considered studies was clinically relevant. PMID- 26351744 TI - Effect of a repeated jaw motor task on masseter muscle performance. AB - OBJECTIVE: The aim of this study was to investigate the effects of 5-days repeated jaw-motor tasks on masseter muscle accuracy performance. DESIGN: Sixteen healthy participants performed a tooth-clenching task (TCT) of 58-minutes on five consecutive days. During measurements, electromyography (EMG) of both masseter muscles was recorded. Each day, the 100% maximum voluntary contraction (MVC) level was determined before the TCT. In the first and third TCT series, participants were instructed to target force levels without visual feedback. During the second TCT series, visual feedback on muscle activity level was displayed. One series consisted of three force levels (10%, 20%, and 40% MVC). In the series, participants alternated between a 30-s rest-block and a 30-s task block for 360 s. In the task-block, participants alternated between a 5-s rest block and a 5-s task-block. EMG activity during epochs of 5-s was quantified by calculation of the root-mean-square (RMS) values. To evaluate the accuracy of the performance, the coefficient of determination (CD) of the target force level-EMG curve was calculated from all series. RESULTS: No significant day-to-day differences in EMG RMS amplitudes were observed during MVC. CDs differed significantly between the five days (P<0.001). CDs in the first series on day 1 were significantly lower than CDs in the first series on days 4 and 5 (P<0.05). CONCLUSIONS: The findings suggest that a rigorous training paradigm may improve the performance of masseter muscles in terms of accuracy but not MVC. This might have implications for understanding the rehabilitation of patients with functional disorders in the stomatognathic system. PMID- 26351745 TI - The cariogenicity of hydrolyzed starch foods by measuring the polyacrylamide hydroxyapatite (PAHA) disc. AB - OBJECTIVES: This study measured the degree of demineralization of starch foods affected by hydrolyzed starch in total starch using the polyacrylamide hydroxyapatite (PAHA) disc. DESIGN: A total of 10 ml of test food was added to a PAHA disc and 5 ml artificial saliva, followed by inoculation with 1 MUl of S. mutans and incubation at 37 degrees C for 180 min. The demineralization effects were then determined using CLSM. RESULTS: The proportion of hydrolyzed starch in total starch in potato increased over time, while hydrolyzed starch in other test food decreased. When the amount of hydrolyzed starch in total starch increased after 180 min (p=0.000), the surface roughness of the PAHA disc in potato was significantly decreased. Wheat-based sugary snacks, such as chips and cookie, had relatively high cariogenic potentials, whereas baked potato had a relatively low cariogenic potential. CONCLUSIONS: Hydrolyzed starch in total starch increased over time, and cariogenic potential was notably decreased. Measurement of PAHA disc may be a valid method for assessing the cariogenic potential of hydrolyzed starch foods. PMID- 26351746 TI - The effect of physical exercise on salivary secretion of MUC5B, amylase and lysozyme. AB - OBJECTIVES: Saliva secretion is regulated by the autonomic nervous system. Parasympathic stimuli increase the secretion of water and mucin MUC5B, whereas sympathetic stimuli such as physical exercise increase the secretion of amylase and other proteins. In the present study we investigated the effect of physical exercise, as a sympathetic stimulus, on salivary flow rate and output of MUC5B, amylase, lysozyme and total protein. DESIGN: Unstimulated whole saliva was collected before exercise (1), after 10 min exercise with moderate intensity by running with a heart rate around 130 beats per minute (2), followed by 10 min exercise with high intensity by running to exhaustion (3) and after 30 min recovery (4). Salivary flow rate, protein and MUC5B concentration, and amylase and lysozyme activity were determined. Saliva protein composition was analysed using SDS-PAGE and immunoblotting. RESULTS: Salivary flow rate, protein and lysozyme secretion increased after exercise with moderate intensity and increased further after exercise with high intensity (p<0.01). Amylase and MUC5B increased after exercise with moderate intensity (p<0.0001), but did not differ significantly between moderate and high exercise intensity. SDS-PAGE analysis and immunoblotting showed that, especially after exercise with high intensity, the concentrations of several other salivary proteins, including MUC7, albumin, and extra-parotid glycoprotein, also increased. CONCLUSIONS: Exercise may not only lead to the anticipated increase in amylase and protein secretion, but also to an increase in salivary flow rate and MUC5B secretion. PMID- 26351747 TI - Tonic activity of the human temporalis muscle at mandibular rest position. AB - OBJECTIVE: There are two theories on the control of the human mandibular rest position; the visco-elastic theory and the muscular theory. In this study, we have searched for evidence for the muscular theory. DESIGN: We have investigated the activity of the anterior temporalis muscle during various positions of the mandible using intramuscular electrodes. RESULTS: In nine out of ten subjects tonic activity in the anterior temporalis muscle during the mandibular rest position was observed. Most of these units ceased firing under the jaw dropped condition of the mandible. CONCLUSIONS: Current findings support the muscular theory since single motor unit activity during the rest position of the mandible is observed in the anterior temporalis. We do not however have any evidence against the visco-elastic theory which may contribute in part to maintain the rest position of the mandible. PMID- 26351748 TI - Salivary flow rate and biochemical composition analysis in stimulated whole saliva of children with cystic fibrosis. AB - OBJECTIVE: It is recognized that cystic fibrosis (CF) patients present a risk for oral diseases, since it affects exocrine glands, and the treatment consists of a carbohydrate-rich diet. Recognizing the protective function of saliva on maintaining oral health, the aim of the study was to evaluate salivary parameters in stimulated whole saliva from children with CF. METHODS: A case-control study was conducted comparing stimulated whole saliva of healthy (n=28; control group) and CF children (n=21; experimental group). Salivary flow rate, initial pH, buffer capacity (total and in each range of pH), total protein and sialic acid (total, free, and conjugated) concentration, alpha-amylase and salivary peroxidase activities were evaluated. Data were compared by two-tailed Student t test (95% CI; p <= 0.05). RESULTS: CF patients presented a significant reduction in salivary parameters compared with the control group (p <= 0.05): salivary flow rate (36%), buffer capacity (pH range from 6.9 to 6.0), sialic acid concentration (total 75%, free 61%, and conjugated 83%); alpha-amylase and salivary peroxidase activities (55%). Additionally, a significant increase in total protein concentration (180%) of stimulated whole saliva from CF patients was verified compared with the control group (p <= 0.05). CONCLUSION: Children with CF presented significant changes in salivary composition, including salivary flow rate, buffering capacity and protective proteins of the oral cavity, compared with children without CF. PMID- 26351749 TI - A combination of cis-2-decenoic acid and chlorhexidine removes dental plaque. AB - OBJECTIVES: To investigate the ability of cis-2-decenoic acid (C2DA) to induce dispersion in single-species biofilms formed by Streptococcus mutans and Candida albicans, as well as to remove their bacterial-fungal dual-species biofilms when combined with low concentrations of chlorhexidine (CHX). METHODS: For biofilm dispersal bioassays, single-species biofilms of S. mutans and C. albicans were grown on the inside surface of petri dishes, using a semi-batch culture method in which the medium was replaced every 24h for 5 days. Biofilms were then treated with very low concentrations of C2DA (100 and 310 nM) for 1h to release cells into the bulk liquid and to evaluate dispersed cell number by measuring the optical density (OD). To assess the ability of C2DA combined CHX treatments to remove tested microorganisms' dual-species biofilms, they were grown on saliva coated hydroxyapatite (sHA) discs for 48 h and then were treated with three different concentrations of CHX (0.08%, 0.06% and 0.04%) alone or in combination with indicated concentrations of C2DA for 1 min twice daily for 3 subsequent days. Biofilms were then either subjected to the field emission scanning electron microscopy (FESEM) analysis or harvested and colony forming units (CFUs) were counted after plating on agar. RESULTS: Treatment of pre-established biofilms with 310 nM C2DA caused an approximately two-fold increase in the number of planktonic cells in both cultures. A combination of 310 nM C2DA and 0.04% CHX resulted in significant removal (p-value <0.05) of dual-species biofilms from sHA discs surface. CONCLUSIONS: Anti-biofilm characteristic of C2DA boosts the action of CHX even at low concentrations. PMID- 26351750 TI - High frequency of p16 and p14 promoter hypermethylation and marked telomere instability in salivary gland tumors. AB - OBJECTIVES: to investigate p16(INK4a) and p14(ARF) tumor suppressor gene methylation status, determine telomere length and assess the importance of these epigenetic and genetic parameters in the development of pleomorphic adenoma and carcinoma ex pleomorphic adenoma of the parotid salivary glands. MATERIALS AND METHODS: Genomic DNA from paraffin-embedded samples of 50 pleomorphic adenomas and 10 carcinomas ex pleomorphic adenoma was subjected to methylation specific polymerase chain reaction for hypermethylation analyses and real time polymerase chain reaction for the relative telomere length calculations. RESULTS: Promoter hypermethylation of the two genes was a very frequent event in both neoplasms - between 60% and 90% of samples were hypermethylated - but without significant difference between the groups. The mean relative telomere length in the pleomorphic adenoma group was significantly increased in comparison to the control group (P=0.00), and significantly decreased in comparison to the carcinoma group (P=0.05). Telomeres were also longer in myxoid and cellular histological subtypes of adenomas than in the classic type (P=0.044 and P=0.018, respectively). Longer telomeres were more frequent in tumors with hypermethylated p14(ARF) alleles (P=0.013). CONCLUSION: Promoter hypermethylations seems to be an important mechanism of p16(INK4a) and p14(ARF) inactivation in parotid gland tumors. Telomeric lengthening appears to be involved in the pathogenesis of both benign and malignant tumors of the parotid glands. PMID- 26351751 TI - Rosiglitazone exerts neuroprotective effects via the suppression of neuronal autophagy and apoptosis in the cortex following traumatic brain injury. AB - Traumatic brain injury (TBI) is one of the leading causes of mortality and morbidity in adults and children worldwide. Recent studies have demonstrated that both apoptosis and autophagy participate in TBI-induced neuronal cell death and functional loss. The peroxisome proliferator-activated receptor-gamma (PPAR gamma) agonist rosiglitazone (RSG) is a well-known anti-inflammatory, which carries out its effects via the activation of PPAR-gamma. Previous studies have suggested that RSG may exert neuroprotective effects in animal models of both chronic and acute brain injury; however, whether RSG is involved in autophagic neuronal death following TBI remains to be elucidated. The present study aimed to determine whether RSG carries out its neuroprotective properties via the attenuation of neuronal apoptosis and autophagy, following TBI in a rat model. Furthermore, the role of RSG was investigated with regards to the modulation of inflammation and glutamate excitotoxicity, and the impact of RSG on functional recovery following TBI was determined. The rats were subjected to controlled cortical impact injury, prior to being randomly divided into three groups: A sham operated group, a TBI group, and an RSG treatment group. The RSG treatment group was intraperitoneally treated with 2 mg/kg RSG immediately after TBI. The results of the present study demonstrated that RSG treatment following TBI significantly reduced neuronal apoptosis and autophagy, and increased functional recovery. These effects were correlated with a decrease in the protein expression levels of tumor necrosis factor alpha and interleukin-6. However, no significant changes were observed in the protein expression levels of glutamate transporter-1 in the brain cortex. The results of the present study provide in vivo evidence that RSG may exert neuroprotective effects via the inhibition of neuronal apoptosis and autophagy following experimental TBI in rats, and the mechanism underlying these effects may be associated with the anti-inflammatory action of RSG. The present study offers a novel insight into the potential use of RSG as a neuroprotective agent for the treatment of cerebral injuries. PMID- 26351753 TI - Giant Perianal Mass. PMID- 26351755 TI - Predicting suitable optoelectronic properties of monoclinic VON semiconductor crystals for photovoltaics using accurate first-principles computations. AB - Using accurate first-principles quantum calculations based on DFT (including the DFPT) with the range-separated hybrid HSE06 exchange-correlation functional, we can predict the essential fundamental properties (such as bandgap, optical absorption co-efficient, dielectric constant, charge carrier effective masses and exciton binding energy) of two stable monoclinic vanadium oxynitride (VON) semiconductor crystals for solar energy conversion applications. In addition to the predicted band gaps in the optimal range for making single-junction solar cells, both polymorphs exhibit a relatively high absorption efficiency in the visible range, high dielectric constant, high charge carrier mobility and much lower exciton binding energy than the thermal energy at room temperature. Moreover, their optical absorption, dielectric and exciton dissociation properties were found to be better than those obtained for semiconductors frequently utilized in photovoltaic devices such as Si, CdTe and GaAs. These novel results offer a great opportunity for this stoichiometric VON material to be properly synthesized and considered as a new good candidate for photovoltaic applications. PMID- 26351754 TI - Respiratory motor function in individuals with centronuclear myopathies. AB - I NTRODUCTION: Individuals with X-linked myotubular myopathy (XLMTM) and other centronuclear myopathies (CNMs) frequently have profound respiratory insufficiency that requires support early in life. Still, few quantitative data exist to characterize respiratory motor function in CNM. METHODS: We evaluated the reliance upon mechanical ventilation (MV), ventilatory kinematics, unassisted tidal volumes, and maximal respiratory pressures in 14 individuals with CNMs, including 10 boys with XLMTM. RESULTS: Thirteen participants required full-time, invasive MV. Maximal inspiratory pressures were higher in subjects who breathed unsupported at least 1 hour/day as compared with 24-hour MV users [33.7 (11.9 42.3) vs. 8.4 (6.0-10.9) cm H(2)O, P < 0.05]. Years of MV dependence correlated significantly with MEP (r = -0.715, P < 0.01). CONCLUSIONS: Respiratory function in CNMs may be related to deconditioning from prolonged MV and/or differences in residual respiratory muscle strength. Results from this study may assist in evaluating severe respiratory insufficiency in neuromuscular clinical care and research. PMID- 26351756 TI - A biologically based neural system coordinates the joints and legs of a tetrapod. AB - A biologically inspired neural control system has been developed that coordinates a tetrapod trotting gait in the sagittal plane. The developed neuromechanical system is used to explore properties of connections in inter-leg and intra-leg coordination. The neural controller is built with biologically based neurons and synapses, and connections are based on data from literature where available. It is applied to a planar biomechanical model of a rat with 14 joints, each actuated by a pair of antagonistic Hill muscle models. The controller generates tension in the muscles through activation of simulated motoneurons. The hind leg and inter leg control networks are based on pathways discovered in cat research tuned to the kinematic motions of a rat. The foreleg network was developed by extrapolating analogous pathways from the hind legs. The formulated intra-leg and inter-leg networks properly coordinate the joints and produce motions similar to those of a walking rat. Changing the strength of a single inter-leg connection is sufficient to account for differences in phase timing in different trotting rats. PMID- 26351757 TI - Chemical sensing properties of Takifugu TRPA1. AB - Transient receptor potential ankyrin 1 (TRPA1) is one of the main sensors for noxious stimuli in animals. Recent studies on the cloning and characterization of TRPA1 channels from several organisms showed the functional diversity of TRPA1 in sensing chemicals and temperature. Nociceptive receptors have been suggested to play important roles in adaptation to the environment by and survival strategies of animals; therefore, the sensitivity of various vertebrate TRPA1s needs to be examined in more detail. Here, we focused on fish TRPA1s and investigated the chemical sensing properties of pufferfish (Takifugu) TRPA1 (pfTRPA1). We determined how mammalian TRPA1 ligands activated pfTRPA1 using a Ca-imaging technique. The results obtained indicated that the sensitivity of pfTRPA1 to known TRPA1 ligands was lower than that of mammalian TRPA1s, except for the response ability to allyl isothiocyanate. We also investigated the effects of tannic acid, a type of polyphenol, by measuring ionic currents in Xenopus oocytes in a two-electrode voltage clamp. Although mouse TRPA1 was inhibited by tannic acid, pfTRPA1 channels were enhanced by the treatment with tannic acid. Taken together, these results suggest that pfTRPA1 is not a simple sensor with a lower sensitivity to chemical stimulation, but is actually a specialized sensor with unique properties. PMID- 26351758 TI - Adult neural precursor cells form connexin-dependent networks that improve their survival. AB - Establishment of cellular networks and calcium homeostasis are essential for embryonic stem cell proliferation and differentiation. We also hypothesized that adult neural progenitor cells form functional cellular networks relevant for their development. We isolated neuronal progenitor cells from the subventricular zone of 5-week-old mice to investigate the role of gap junctions, calcium homeostasis, and cellular networks in cell differentiation and survival. Western blotting and reverse transcription-PCR showed that the cells expressed the gap junction components connexin 26, 36, 43, and 45, and that expression of connexin 43 increased in early (8 days) differentiated cells. Transmission electron microscopy and immunocytochemistry also indicated that gap junctions were present. Scrape-loading experiments showed dye transfer between cells that could be prevented by gapjunction blockers; thus, functional intercellular gap junctions had been established. However, dye transfer was four times stronger in differentiated cultures, correlating with the increased connexin 43 expression. During time-lapse calcium imaging, both differentiated and undifferentiated cultures showed spontaneous calcium activity that was reduced by gap junction blockers. Cross-correlation analysis of the calcium recordings showed that the cells were interconnected through gap junctions and that the early-differentiated cells were organized in small-world networks. Gap junction blockers did not affect proliferation and differentiation, but resulted in twice as many apoptotic cells. mRNAi knockdown of connexin 43 also doubled the number of apoptotic cells. We conclude that adult neural progenitor cells form networks in vitro that are strengthened during early differentiation by increased expression of connexin 43. The networks are functional and improve cell survival. PMID- 26351760 TI - [Para- and Postpneumonic Pleural Empyema: Current Treatment Strategies in Children and Adults]. AB - INTRODUCTION: Parapneumonic pleural effusions arise from pneumonia and may develop into pleural empyema (PE). PE is defined as collection of pus in the pleural space with secondary inflammation of the visceral and parietal pleura. This review article describes the current treatment strategies for para- and postpneumonic PE both in children and adults. MATERIAL AND METHODS: Selective literature research via Medline (key words: pleural empyema, pleural empyema in children, thoracic empyema) and presentation of our own clinical experience with therapy recommendations. RESULTS: The incidence of postpneumonic PE is increasing in both children and adults. PE is associated with a high morbidity and mortality if it is not treated early and adequate. Progression of PE follows a characteristic morphological course, which is classified in three stages: the exsudative, fibrinopurulent, and organizing phase. Treatment should be adapted to these three phases including systemic antibiotic therapy and drainage of the pleural space. Intrapleural fibrinolysis can be performed with good success independent of age in the transition of stage 1 and 2. In persistent PE (stage 2), thoracoscopic decortication is recommended to avoid progression into the organizing phase (stage 3) with the need of an open decortication. In debilitated elderly patients the increasing use of intrathoracic vacuum therapy (Mini VAC/Mini-VAC-instill) offers an effective and less invasive therapy option. CONCLUSION: Para- and postpneumonic PE requires an individualized and stage adapted therapy using a combination of medical and surgical treatment strategies with the aims of removing the source of infection and ensuring re-establishment of lung expansion. PMID- 26351759 TI - Neuroimmune interactions in itch: Do chronic itch, chronic pain, and chronic cough share similar mechanisms? AB - Itch and pain are closely related but also clearly distinct sensations. Pain is known to suppress itch, while analgesics such as morphine can provoke itch. However, in pathological and chronic conditions, pain and itch also have similarities. Dysfunction of the nervous system, as manifested by neural plastic changes in primary sensory neurons of the peripheral nervous system (peripheral sensitization) and spinal cord and brain stem neurons in the central nervous system (central sensitization) will result in chronic pain and itch. Importantly, these diseases also result from immune dysfunction, since inflammatory mediators can directly activate or sensitize nociceptive and pruriceptive neurons in the peripheral and central nervous system, leading to pain and itch hypersensitivity. In this mini-review, I discuss the roles of Toll-like receptors (TLRs), transient receptor potential ankyrin 1 (TRPA1) ion channel, and Nav1.7 sodium channel in regulating itch and inflammation, with special emphasis of neuronal TLR signaling and the interaction of TLR7 and TRPA1. Chronic pain and chronic itch are debilitating diseases and dramatically impact the life quality of patients. Targeting TLRs for the control of inflammation, neuroinflammation (inflammation restricted in the nervous system), and hyperexcitability of nociceptors and pruriceptors will lead to new therapeutics for the relief of chronic pain and chronic itch. Finally, given the shared mechanisms among chronic cough, chronic pain, and chronic itch and the demonstrated efficacy of the neuropathic pain drug gabapentin in treating chronic cough, novel therapeutics targeting TRPA1, Nav1.7, and TLRs may also help to alleviate refractory cough via modulating neuron-immune interaction. PMID- 26351761 TI - [Pulmonary Echinococcosis: Surgical Aspects]. AB - Pulmonary cystic echinococcosis is a very rare disease in Germany. It is caused by the larvae of the dog tapeworm (echinococcus granulosus). The liver is the most affected organ, followed by the lungs. Surgery remains the main therapeutic approach for pulmonary CE. Whenever possible, parenchyma-preserving lung surgery should be preferred over anatomic lung resections. To ensure best therapeutic results, surgery needs to be performed under precise consideration of important infectiological aspects and patients should be treated in specialised centres based on interdisciplinary consensus. In addition to surgical aspects, this review summarises special infectiological features of this disease, which are crucial to the surgical approach. PMID- 26351762 TI - [Pulmonary Tuberculosis--Is Surgery still Necessary?]. AB - BACKGROUND: Tuberculosis is still one of the most common infectious diseases along with HIV and malaria and therefore represents a serious problem in the health sector. Due to immigrants and refugees, the disease is also present in Europe. The global increase of multidrug resistant tuberculosis leads to a highly significant and current importance of sufficient therapeutic measures. In recent years, this fact has led to a reevaluation of surgical therapy in the context of an interdisciplinary and multimodal treatment of multidrug resistant tuberculosis. In addition, despite an effective treatment of drug sensitive tuberculosis with antibiotics, there are still indications for surgery in the treatment of tuberculosis. Beside massive hemoptysis as an emergency indication for surgical intervention, secondary complications of tuberculosis such as aspergilloma, chronic hemoptysis, pneumothorax, bronchopleural fistula and destroyed lung remain indications for surgery. CONCLUSION: The indication for surgery should always be made in a multimodal therapeutic approach by an interdisciplinary team, taking patient age and functional analysis into account. Effective antibiotic therapy should be performed before and after surgery in order to achieve a sustained treatment success. PMID- 26351763 TI - [Pulmonary Aspergilloma: Indications for Surgery and Surgical Techniques]. AB - Aspergillus species may infect preexisting lung cavities and cause pulmonary aspergillomas, which may lead to life-threatening haemoptysis. The objective of this review article is to summarise current strategies for the management of pulmonary aspergillomas. Symptomatic aspergillomas should be treated surgically, with lobectomy being the treatment of choice. Minimally-invasive approaches may be appropriate in selected cases. The role of perioperative antifungal therapy in immunocompetent patients remains controversial. Antimycotic treatment and embolisation of bronchial arteries may be useful treatment options for inoperable patients. PMID- 26351764 TI - [Management of Lung Abscess]. AB - A lung abscess is an infectious pulmonary disease characterised by the presence of a pus-filled cavity within the lung parenchyma. The content of an abscess often drains into the airways spontaneously, leading to an air-fluid level visible on chest X-rays and CT scans. Primary lung abscesses occur in patients who are prone to aspiration or in otherwise healthy individuals; secondary lung abscesses typically develop in association with a stenosing lung neoplasm or a systemic disease that compromises immune defences, such as AIDS, or after organ transplantation. The organisms found in abscesses caused by aspiration pneumonia reflect the resident flora of the oropharynx. The most commonly isolated organisms are anaerobic bacteria (Prevotella, Bacteroides, Fusobacterium, Peptostreptococcus) or streptococci; in alcoholics with poor oral hygiene, the spectrum of pathogens includes Staphylococcus aureus, Streptococcus pyogenes and Actinomyces. Chest radiography and computed tomography (CT) are mandatory procedures in the diagnostic algorithm. Standard treatment for a lung abscess consists of systemic antibiotic therapy, which is based on the anticipated or proven bacterial spectrum of the abscess. In most cases, primary abscesses are successfully treated by calculated empiric antibiotic therapy, with an estimated lethality rate of less than 10 %. Secondary abscesses, despite targeted antimicrobial therapy, are associated with a poor prognosis, which depends on the patient's general condition and underlying disease; lethality is as high as 75 %. Negative prognostic factors are old age, severe comorbidities, immunosuppression, bronchial obstruction, and neoplasms. Surgical intervention due to failure of conservative treatment is required in only 10 % of patients, with a success rate of up to 90 % and postoperative mortality rates ranging between 0 and 33 %. Treatment success after endoscopic or percutaneous drainage is achieved in 73 to 100 % of cases, with an acceptable mortality rate (0-9 %). PMID- 26351766 TI - [Editorial]. PMID- 26351767 TI - [Mediastinitis: Clinical Presentation and Therapy]. AB - Acute infection of the mediastinum remains a condition with high morbidity and lethality rates. The manifestation and course of the illness vary widely depending on the cause of infection. Lack of knowledge or awareness of the illness and mostly unspecific clinical symptoms often delay diagnosis and thereby the start of adequate therapy. Computed tomography (CT) of the neck and thorax is the method of choice for diagnostics and control of therapeutic success. An early diagnosis with immediate surgical debridement and drainage of all infected tissue compartments, as well as strict sepsis therapy, are decisive for the prognosis. PMID- 26351768 TI - Acute diarrhea: evidence-based management. AB - OBJECTIVES: To describe the current recommendations on the best management of pediatric patients with acute diarrheal disease. DATA SOURCE: PubMed, Scopus, Google Scholar. DATA SUMMARY: There has been little progress in the use of oral rehydration salts (ORS) in recent decades, despite being widely reported by international guidelines. Several studies have been performed to improve the effectiveness of ORS. Intravenous hydration with isotonic saline solution, quickly infused, should be given in cases of severe dehydration. Nutrition should be ensured after the dehydration resolution, and is essential for intestinal and immune health. Dietary restrictions are usually not beneficial and may be harmful. Symptomatic medications have limited indication and antibiotics are indicated in specific cases, such as cholera and moderate to severe shigellosis. CONCLUSIONS: Hydration and nutrition are the interventions with the greatest impact on the course of acute diarrhea. PMID- 26351769 TI - The pediatrician's role in the first thousand days of the child: the pursuit of healthy nutrition and development. AB - OBJECTIVES: To describe the concept of the first 1000 days, its importance for health, and actions to be implemented, particularly by pediatricians, in order to attain healthy nutrition and development. SOURCES: A nonsystematic review was carried out in the SciELO, LILACS, MEDLINE, Scopus, and Web of Science databases, encompassing the last decade, using the terms 1000 days, child nutrition, child development, childhood, and child. A non-systematic search was performed online for organizations that use the 1000-day concept and give recommendations on children's health. SUMMARY OF THE FINDINGS: The first 1000 days range from conception to the end of the second year of life. It represents an important period to implement interventions to ensure healthy nutrition and development, which will bring benefits throughout life. Children should receive adequate nutrition, through proper prenatal diet, exclusive breastfeeding for the first 6 months, addition of adequate complementary foods, and continued breastfeeding up to 2 years of life. Given the condition of absolute dependence on an adult's care, it is crucial to establish an enabling and friendly environment, necessary for the development of strong bonds with caregivers, laying the groundwork for a full and healthy development. CONCLUSIONS: The pediatrician, together with other professionals, can act by promoting actions emphasizing the concept of the first 1000 days to ensure healthy nutrition and development. Focusing on actions in this period may increase the child's chance of having a healthy and productive life in the future, strengthening family and community ties, helping to break the intergenerational cycle of poverty. PMID- 26351770 TI - Improved sensitivity and specificity for prostate cancer diagnosis based on the urine PCA3/PSA ratio acquired by sequence-specific RNA capture. AB - Prostate cancer antigen 3 (PCA3) is a non-coding RNA fragment that is overexpressed in prostate cancer cells. However, the clinical applications of PCA3 are highly limited due to the instability of RNA and the lack of reliable and efficient RNA extraction and purification methods. Thus, in the present study, we compared three different methods of RNA extraction to further confirm the higher yield of commercial magnetic beads with poly-T functionalization and a capturer strand. The current protocols for RNA extraction of i) the phenol chloroform method, ii) the affinity column method and iii) magnetic beads with poly-T functionalization and a capturer strand were applied separately for RNA extraction in urine samples. Reverse transcription-quantitative polymerase chain reaction was performed to evaluate the yield of the three methods of RNA extraction. Furthermore, 52 urine samples after prostate massage from patients suspected of a diagnosis of prostate cancer were collected. The Mag-Cap method and RT-PCR were applied to obtain the PCA3 score. The clinical value of the PCA3 score was investigated by comparison with the pathology of the prostate biopsy. The yield of the Mag-Cap method was higher than that of the phenol-chloroform method and commercial kits. Thirty-four patients were pathologically diagnosed with prostate cancer and 18 with benign prostatic hyperplasia (BPH). It was confirmed that the median PCA3 score was higher among the prostate cancer patients than those with benign disease (53.5 vs. 17, p=0.000). A sensitivity of 82.4% and a specificity of 77.8% were obtained when the cut-off value for the PCA3 score was 28.5. The Mag-Cap method was found to be more efficient for RNA extraction. The urinary PCA3 score is a promising method for prostate cancer screening, detection and diagnosis, and has the potential to reduce unnecessary prostate biopsies. PMID- 26351771 TI - Cigarette smoke modulates PC3 prostate cancer cell migration by altering adhesion molecules and the extracellular matrix. AB - Prostate cancer (PCa) is the second leading cause of cancer-related mortality among American males. Studies suggest that cigarette smoking is associated with the progression of PCa; however, the molecular mechanisms underlying this process have not been extensively investigated. PCa progression is characterized by increased cell migration and alterations in extracellular matrix (ECM)- and cell adhesion molecule (CAM)-related gene expression. In the present study, the influence of cigarette smoke medium (SM) on cell migration and on the expression of ECM- and CAM-related genes in PC3 prostate adenocarcinoma cells was investigated. According to a wound-healing assay, SM treatment promoted PC3 cell migration. RNA expression levels from SM-treated and control cells were analyzed using a polymerase chain reaction (PCR) array. Of 84 genes analyzed, 27.38% (23/84) exhibited a >=2-fold change in threshold cycle in PC3 cells following 0.5% SM treatment. Functional gene grouping analysis demonstrated that SM treatment modulated the RNA transcription of approximately 18.4% of CAMs and 33.93% of ECM-related genes. Quantitative PCR analysis showed that SM treatment led to a significant decrease in transcription levels of the following genes: Collagen 5 alpha-1(V), connective tissue growth factor, integrin beta-2, kallmann syndrome 1, laminin alpha 3, matrix metallopeptidase 7 (MMP7), MMP13, secreted protein acidic cysteine-rich, thrombospondin-2 and versican; and that SM significantly increased the transcription levels of MMP2 and MMP12. Furthermore, MMP2 knockdown significantly reduced the migration of SM-treated PC3 cells. The present study provides novel insights into the association of cigarette smoking with PCa progression, via the alteration of ECM/CAM interactions. PMID- 26351773 TI - Immunodetection of telomerase-like immunoreactivity in normal and regenerating tail of amphibians suggests it is related to their regenerative capacity. AB - The high regenerative power of amphibians suggests that numerous signaling pathways remain active in larvae and adult tissues, including those stimulated by telomerases. The protein component of Telomerase (TERT) shows high amino acid homology in numerous vertebrates and we have utilized an antibody made for a lizard telomerase to detect a putative telomerase in amphibians tissues based on 60-75% epitope identity. Western blotting studies indicate that telomerase is constitutionally present in normal and regenerating tails of tadpoles of the anuran Rana dalmatina. In the neotenic urodele Ambystoma mexicanum the enzyme is detectable in the normal tail and increases during tail regeneration. Immunofluorescence shows that telomerase is localized in both epidermal and mesenchymal cells of normal and regenerating tail of A. mexicanum, especially in their nuclei. The ultrastructural localization with gold or gold-silver intensified confirms that telomerase is mainly present in the nucleus, in particular in discrete regions of the nucleoplasm identified as Cajal bodies and in the nucleolus, sites known in mammalian cells to be involved in the processing of the enzyme. Telomerases are present in normal and even more in regenerating tissues, and are possibly implicated in the numerous cell replications needed for physiological or post-amputation tissue regeneration in amphibians. J. Exp. Zool. 323A: 757-766, 2015. (c) 2015 Wiley Periodicals, Inc. PMID- 26351772 TI - Effectiveness of plasma treatment on pancreatic cancer cells. AB - Non-equilibrium atmospheric pressure plasma (NEAPP) has attracted attention in cancer therapy. We explored the indirect effect of NEAPP through plasma-activated medium (PAM) on pancreatic cancer cells in vitro and in vivo. In this study, four pancreatic cancer cell lines were used and the antitumor effects of PAM treatment were evaluated using a cell proliferation assay. To explore functional mechanisms, morphological change and caspase-3/7 activation in cells were also assessed. Furthermore, reactive oxygen species (ROS) generation in cells was examined and N-acetyl cysteine (NAC), an intracellular ROS scavenger, was tested. Finally, the antitumor effect of local injection of PAM was investigated in a mouse xenograft model. We found that PAM treatment had lethal effect on pancreatic cancer cells. Typical morphological findings suggestive of apoptosis such as vacuolization of cell membranes, small and round cells and aggregation of cell nuclei, were observed in the PAM treated cells. Caspase-3/7 activation was detected in accordance with the observed morphological changes. Additionally, ROS uptake was observed in all cell lines tested, while the antitumor effects of PAM were completely inhibited with NAC. In the mouse xenograft model, the calculated tumor volume on day 28 in the PAM treatment group was significantly smaller compared with the control group [28 +/- 22 vs. 89 +/- 38 (mm(3) +/- SD), p=0.0031]. These results show that PAM treatment of pancreatic cancer might be a promising therapeutic strategy. PMID- 26351774 TI - Use of Health Care System-Supplied Aspirin by Veterans With Postoperative Heart Attack or Unstable Angina. AB - Evidence-based guidelines for the use of aspirin in secondary prevention of cardiovascular disease events are well established. Despite this, the prevalence of aspirin use for secondary prevention is suboptimal. The study aimed to determine the prevalence of aspirin use for secondary prevention of cardiovascular disease events when it is dispensed as a prescription, as is performed in the Veterans Affairs (VA) managed care system. VA patients who had undergone major surgery and experienced a postoperative myocardial infarction (MI) or unstable angina between the years 2005 and 2009 were identified from administrative databases. VA pharmacy records were used to determine whether a prescription for aspirin was filled after the postoperative MI or unstable angina. Multivariable logistic regression models estimated odd ratios of filling aspirin prescriptions for the predictors of interest. Of the 321,131 men and women veterans who underwent major surgery, 7,700 experienced a postoperative MI or unstable angina. Among those 7,700, 47% filled an aspirin prescription. Only 59% of veterans with no co-pay filled an aspirin prescription. Aspirin fills were more common in younger veterans, Blacks, Hispanics, males, hypertensive veterans, mentally ill patients, those with no co-pay and those prescribed antiplatelets/anticoagulants in addition to aspirin postoperatively. These findings suggest that the impact of dispensing aspirin as a prescription may not be significant in increasing the appropriate use of aspirin for secondary prevention. PMID- 26351775 TI - Positive Association of the Cathepsin D Ala224Val Gene Polymorphism With the Risk of Alzheimer's Disease. AB - BACKGROUND: Alzheimer's disease (AD) is the most common cause of senile dementia. In Ecuador, the number of deaths caused by AD increases each year. Epidemiologically, the Ecuadorian population is composed of a mixture of several genetic backgrounds along with environmental factors, that make it unique and ideal for population studies. The main objective of this study was to determine the prevalence of Cystatin C (CST3), Cathepsin D (CTSD) and Manganese superoxide dismutase (MnSOD) amino acid-altering polymorphisms and their influence on the development of AD in the Ecuadorian population. METHODS: This is a case-control study consisting of 56 patients with AD, from the Department of Neurology at Carlos Andrade Marin Hospital. The control group (n = 55) comprised healthy elderly adults. The inclusion period was from January to August of 2012. Peripheral blood was collected from both groups for DNA extraction, polymerase chain reaction and capillary sequencing. RESULTS: There was a positive association between a CTSD polymorphism (Ala224Val) and the development of AD (odds ratio = 8.1, 95% confidence interval: 0.9-85.7; P < 0.025). However, the 3 other polymorphisms investigated did not show significant associations with AD. CONCLUSIONS: Variations in CTSD and MnSOD showed no association with the development of AD, whereas the presence of the Ala224Val polymorphism in CTSD had a positive association with the development of AD. PMID- 26351776 TI - A Pilot Study to Determine if Vitamin D Repletion Improves Endothelial Function in Lupus Patients. AB - BACKGROUND: The endothelium is important not only in regulating vascular tone but also in modulating inflammation. Patients with systemic lupus erythematosus (SLE) have deficits in these endothelial functions. Vitamin D is a nuclear hormone that regulates vascular endothelial nitric oxide synthase activity and expression. Many SLE patients have insufficient levels of vitamin D. The effect of this hormone on vascular endothelial function in SLE patients is not known. This study was designed to determine the effect size of repleting vitamin D levels on endothelial function in patients with SLE and vitamin D deficiency. METHODS: SLE patients with 25(OH) vitamin D (25(OH)D) levels <20 ng/mL were randomized to oral vitamin D3 (D3) doses that did or did not raise 25(OH)D levels to >=32 ng/mL. Endothelial function was measured with flow-mediated dilation (FMD) before and after 16 weeks of vitamin D3 supplementation. RESULTS: Half of those who achieved 25(OH)D levels of >=32 ng/mL experienced increases in FMD, whereas none of those with continued low 25(OH)D levels did. Those with increases in FMD had significantly higher final 25(OH)D levels. Using the effect size from this study, future studies designed to test the effect of repleting 25(OH)D on FMD in vitamin D-deficient SLE patients will require 35 patients in each group. CONCLUSIONS: These results suggest a potential role for vitamin D in SLE-related endothelial dysfunction and that an adaptive, multi-arm, treat-to-target, serum-level trial design may increase the efficiency and likelihood of success of such a study. PMID- 26351777 TI - High Flow Nasal Cannulas for Oxygenation: An Audit of Its Use in a Tertiary Care Hospital. AB - BACKGROUND: High flow nasal cannulas (HFNCs) provide humidified oxygen at higher flow rates and higher FiO2s than conventional delivery devices and are typically used in special care units. There is limited information on their use in general hospital settings. METHODS: The medical records of all patients who were treated with HFNC during the calendar year 2014 were retrospectively reviewed to collect information on age, sex, indications, arterial blood gases when available, O2 saturations and outcomes. RESULTS: One hundred six patients received oxygen supplementation by HFNC in their hospital in 2014. The average age was 61.6 +/- 16.2 years; 62 patients were men. The indications for HFNC included dyspnea (1 patient), hypoxemic respiratory failure (101 patients) and hypercapneic respiratory failure (4 patients). The PaO2 increased from 68.2 +/- 16.3 mm Hg to 83.1 +/- 32.2 mm Hg (N = 32, P = 0.02) with the change to HFNC. The O2 saturation increased from 93.1 +/- 4.5% to 95.1 +/- 3.0% (N = 106, P = 0.00015). The mean duration of use was 4.3 +/- 3.7 days. Sixty-five patients did not require intubation or noninvasive ventilation (NIV). Sixteen required NIV, 16 required intubation and 9 required both. The overall mortality was 15%. CONCLUSIONS: HFNC oxygen therapy is used relatively frequently in their hospital on surgical and medical services. PaO2s and O2 saturations improved when patients were switched to this mode of oxygenation, but some patients subsequently required NIV and/or intubation. Patients on HFNC need careful monitoring for deterioration in their respiratory status. PMID- 26351779 TI - Synthesis of substituted beta-diketiminate gallium hydrides via oxidative addition of H-O bonds. AB - Oxidative addition of LGa into the OH bonds from HCCCH2OH, Ph2Si(OH)2, (nBuO)2P(O)(OH) and 4-MeC6H4S(O)2(OH) results in the formation of four compounds of the general formula LGa(H)(O-X). The correlation of the Ga-O bond length and the strength of the Ga-H bond depending on the acidity of the OH group in the starting materials has been demonstrated. The molecular structures of all four compounds have been determined using single crystal X-ray diffraction experiments. DFT calculations were performed on the reacting complex of LGa with propargyl alcohol and show an OHGa hydrogen bond as the first interaction between the reagents. This reacting complex changes into a D-A complex where the oxygen atom of the propargyl alcohol coordinates to the gallium atom and in a concerted reaction the oxidative addition product is formed. PMID- 26351778 TI - Anti-CD47 antibody suppresses tumour growth and augments the effect of chemotherapy treatment in hepatocellular carcinoma. AB - BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is often associated with metastasis and recurrence leading to a poor prognosis. Therefore, development of novel treatment regimens is urgently needed to improve the survival of HCC patients. In this study, we aimed to investigate the in vitro and in vivo effects of anti-CD47 antibody alone and in combination with chemotherapy in HCC. METHODS: In this study, we examined the functional effects of anti-CD47 antibody (B6H12) on cell proliferation, sphere formation, migration and invasion, chemosensitivity, macrophage-mediated phagocytosis and tumourigenicity both in vitro and in vivo. The therapeutic efficacy of anti-CD47 antibody alone or in combination with doxorubicin was examined in patient-derived HCC xenograft. RESULTS: Blocking CD47 with anti-CD47 monoclonal antibody (B6H12) at 10 MUg/ml could suppress self-renewal, tumourigenicity and migration and invasion abilities of MHCC-97L and Huh-7 cells. Interestingly, anti-CD47 antibody synergized the effect of HCC cells to chemotherapeutic drugs including doxorubicin and cisplatin. Blockade of CD47 by anti-CD47 antibody induced macrophage-mediated phagocytosis. Using a patient-derived HCC xenograft mouse model, we found that anti-CD47 antibody (400 MUg/mouse) in combination with doxorubicin (2 mg/kg) exerted maximal effects on tumour suppression, as compared with doxorubicin and anti-CD47 antibody alone. CONCLUSIONS: Anti-CD47 antibody treatment could complement chemotherapy which may be a promising therapeutic strategy for the treatment of HCC patients. PMID- 26351780 TI - Pharmacodynamic comparison of LY3023703, a novel microsomal prostaglandin e synthase 1 inhibitor, with celecoxib. AB - To assess the safety, tolerability, and pharmacology of LY3023703, a microsomal prostaglandin E synthase 1 (mPGES1) inhibitor, a multiple ascending dose study was conducted. Forty-eight subjects received LY3023703, celecoxib (400 mg), or placebo once daily for 28 days. Compared with placebo, LY3023703 inhibited ex vivo lipopolysaccharide-stimulated prostaglandin E2 (PGE2 ) synthesis 91% and 97% on days 1 and 28, respectively, after 30-mg dosing, comparable to celecoxib's effect (82% inhibition compared to placebo). Unlike celecoxib, which also inhibited prostacyclin synthesis by 44%, LY3023703 demonstrated a maximal increase in prostacyclin synthesis of 115%. Transient elevations of serum aminotransferase were observed in one subject after 30-mg LY3023703 dosing (10* upper limit of normal (ULN)), and one subject after 15-mg dosing (about 1.5* ULN). Results from this study suggest that mPGES1 inhibits inducible PGE synthesis without suppressing prostacyclin generation and presents a novel target for inflammatory pain. PMID- 26351782 TI - Performance of a thrombectomy device for aspiration of thrombus with various sizes based on a computational fluid dynamic modeling. AB - It is important to thoroughly remove the thrombus within the course of aspiration thrombectomy; otherwise, it may lead to further embolization. The performance of the aspiration thrombectomy device with a generic geometry is studied through the computational approach. In order to model the thrombus aspiration, a real left coronary artery is chosen while thrombi with various sizes are located at the bifurcation area of the coronary artery and, depending on the size of the thrombus, it is stretched toward the side branches. The thrombus occupies the artery resembling the blood current obstruction in the coronary vessel similar to the situation that leads to heart attack. It is concluded that the aspiration ability of the thrombectomy device is not linked to the thrombus size; it is rather linked to the aspiration pressure and thrombus age (organized versus fresh thrombus). However, the aspiration time period correlates to the thrombus size. The minimum applicable aspiration pressure is also investigated in this study. PMID- 26351781 TI - CD24 expression as a marker for predicting clinical outcome and invasive activity in uterine cervical cancer. AB - CD24, a small heavily glycosylated mucin-like glycosyl-phosphatidylinositol anchored cell surface protein, plays an important role in the carcinogenesis of various human malignancies. However, its function in cervical cancer remains unclear. The aim of the present study was to evaluate the expression of CD24 clinicopathologically and to analyze its functional behavior biologically in cervical cancer. A total of 117 uterine cervical cancer tumors were immunohistochemically analyzed using a CD24 monoclonal antibody on paraffin blocks. We also examined whether CD24 enhanced the invasive activity or the Akt, ERK, NF-kappaB and MMP activity in a uterine cervical cancer cell line (CaSki) by a western blot analysis. The patients with enhanced CD24 expression had a higher rate of advanced clinical stage (50 vs. 16.5%, p<0.01), lymph node metastasis (34.6 vs. 14.3%) and lymphovascular involvement (65.4 vs. 20.4%, p=0.01), and a poor overall and disease-free survival (5-year survival rate: 62 vs. 86%, p=0.03). CD24 overexpression in CaSki cells resulted in activation of Cell Signaling proteins, including Akt, ERK, NF-kappaB and MMP-9. An invasion assay showed that CD24 overexpression in CaSki cells led to increased invasion ability. The CD24 overexpression also increased mRNA expression of Slug but not Snail. Moreover, the CD24 overexpression also decreased expression of E-cadherin and increased N-cadherin protein levels. Increased expression of CD24 may be associated with tumor progression and prognosis in patients with uterine cervical cancer. CD24 expression may therefore be used not only as a prognostic marker in uterine cervical cancer, but also as a target for the development of new therapeutic approaches. PMID- 26351784 TI - Means to increase the therapeutic efficiency of magnetic heating of tumors. AB - The treatment of tumors via hyperthermia has gained increased attention in the last years. Among the different modalities available so far, magnetic hyperthermia has the particular advantage of offering the possibility of depositing the heating source directly into the tumor. In this study, we summarized the present knowledge we gained on how to improve the therapeutic efficiency of magnetic hyperthermia using magnetic nanoparticles (MNPs), with particular consideration of the intratumoral infiltration of the magnetic material. We found that (1) MNPs will be mainly immobilized at the tumor area and that this aspect has to be considered when estimating the heating potential of MNPs, (2) the intratumoral distribution patterns via slow infiltration might well be modulated by specific MNP coating and magnetic targeting, (3) imaging of the nanoparticle depositions within the tumor might allow to correct the distribution pattern via multiple applications, (4) multiple therapeutic sessions are feasible because MNPs are not delivered from the tumor site during the heating process, (5) the utilization of MNPs that internalize into cells will favor the production of intracellular heating spots rather than extracellular ones, (6) utilization of MNPs functionalized with chemotherapeutic agents will allow us to exploit the additive effects of both therapeutic modalities, and (7) distinct cytopathological and histopathological alterations in target tissues are induced as a result of magnetic hyperthermia. However, the accumulation at the tumor via intravenous application remains a matter of challenge. PMID- 26351783 TI - Magnetic nanoparticles for magnetic drug targeting. AB - Nanomedicine and superparamagnetic iron oxide nanoparticles (SPIONs) are thought to have an important impact on medicine in the future. Especially in cancer therapy, SPIONs offer the opportunity of improving the effectivity of the treatment and reduce side effects by magnetic accumulation of SPION-bound chemotherapeutics in the tumor area. Although still some challenges have to be overcome, before the new treatment concept of magnetic drug targeting will reach the patients, substantial progress has been made, and promising results were shown in the last years. PMID- 26351785 TI - Biomechanical effect of different femoral neck blade position on the fixation of intertrochanteric fracture: a finite element analysis. AB - Medial migration or cutout of the neck helical blade has commonly occurred in the treatment of trochanteric fracture of the femur. The position of the helical blade within the femoral head is one of the influencing factors that cause the blade to perforate the intact joint surface; however, the ideal placement of the helical blade is not currently known. A finite element model of a femur/nail construct was utilized to analyze five possible blade positions in the femoral head. Normal strain at the fracture surface, the minimum principal strain in the cancellous bone, and the von Mises stress in the implant itself were calculated and compared between different blade positions. The results showed that a large area of normal compressive strain at the fracture surface was observed in the inferior and posterior blade positions. The volume of cancellous bone strained to yielding in the femoral head and neck was lower for the inferior and posterior positions, whereas it was the highest for the superior position. The inferior and posterior positions had lower von Mises stress in the implant itself. The inferior and posterior positions may be the ideal position for the intramedullary nail with a helical neck blade. PMID- 26351786 TI - Postoperative Acute Respiratory Failure In Patients Treated Surgically For Goiters. AB - The aim of the study was to present a clinical picture, treatment and prognosis regarding patients who developed acute respiratory failure (ARF) while treated surgically for a goiter. MATERIAL AND METHODS: A total of 3810 patients were treated for goiters between 2008 to 2013. Symptoms of postoperative ARF were recognized in 39 (1%) patients. RESULTS: Symptoms of postoperative ARF were a postoperative hemorrhage in 31 (79.4%), lymphorrhagia in 1 (2.6%), bilateral paralysis of recurrent laryngeal nerves in 6 (15.4%) and acute circulatory - respiratory failure in 1 (2.6%). Postoperative hemorrhage appeared in 19 patients operated for nodular goiter, 4 with a retrosternal nodular goiter, 1x nontoxic recurrent retrosternal nodular goiter, 1x toxic recurrent retrosternal goiter nodular goiter, 2x Graves'goiter and 4x with malignant goiter. The cause of hemorrhage was parenchymal bleeding from the stumps and / or short neck muscles (29x), arterial bleeding (1x) and bleeding into the subcutaneous tissue (1x). Massive lymphorrhagia appeared as a result of damage to the thoracic duct after total thyroidectomy due to papillary thyroid carcinoma with cervical lymph node dissection on the left side. All patients who were diagnosed with bilateral paralysis of RLN, tracheostomy was performed. Of all 39 patients who underwent surgery two died - one in 6 days after surgery due to myocardial infarction, and another as a result of micropulmonary embolism and acute circulatory - respiratory failure in 18 hours after surgery. CONCLUSIONS: 1. The most frequent causes of acute respiratory failure in postoperative period are a hemorrhage from the operation site and bilateral paralysis of recurrent laryngeal nerves. 2. Acute postoperative respiratory failure is an indication for postoperative wound revision. PMID- 26351787 TI - Non-Recurrent Laryngeal Nerve. AB - The aim of the study was to assess the frequency of non-recurrent laryngeal nerves (Non-RLN). MATERIAL AND METHODS: A total of 6110 patients were operated in our hospital between 1 January 2005 and 31 December 2013 for various goiters (5429) and various types of hyperparathyroidism (618). Laryngeal nerve was exposed during operation in 1700 patients from superior aperture of the chest to superior aperture of the larynx. Identification process of RLN was started with dissecting inferior thyroid artery (ITA) and its junction with the nerve. Then main trunk of the nerve was exposed backwards till the region of superior aperture of the chest together with the end portion till the nerve outlet to the larynx. RESULTS: In the group of 1700 patients, RLN was exposed bilaterally in 1400 (82.4%) and unilaterally in 300 (17.6%). In the group of 3100 dissected RLNs the course of RLN was observed on the right side in 1710 patients and on the left in 1390. Irreversible nature RLN was shown in four cases (0.1%) - four women (02%) aged 42-55 (mean 49.3) - three operated for non-toxic nodular goiter and one for primary hyperparathyroidism. Each time the Non-RLN was seen on the right side. The other patients manifested recurrent character RLN. Moreover, interstitial course of RLN was found on the left side in one man. CONCLUSION: Non recurrent laryngeal nerve is a rare anatomical variation, occurring more frequently on the right side. Surgeon during surgery of the thyroid and parathyroid glands should be aware of its existence to avoid damage. PMID- 26351788 TI - Assessment Of Plasma B-Catenin Concentration As Biomarker Of Thyroid Cancer. AB - New diagnostic methods for thyroid diseases are still being searched for. Immunohistochemical diagnosis is expanded by the introduction of new biomarkers including beta-catenin (B-Cat). Associations are indicated between the cellular expression of this biomarker and tumor stage, nodal metastases and the degree of tumor cell differentiation. Reports are scarce regarding the plasma level of this biomarker in malignant neoplastic diseases. The aim of the study was to analyze the plasma B-Cat concentration and the possibility of it use in the diagnostics of patients with nodular goiter and papillary thyroid carcinoma. MATERIAL AND METHODS: Plasma B-Cat concentration was determined in 64 patients with goiter and 15 healthy volunteers. The final histopathological examination revealed 41 cases of papillary thyroid carcinoma (PTC) and 13 cases of nodular goiter (NG). RESULTS: A significant increase in B-Cat (p <0.05) in both groups compared to the control group. No differences in the concentrations of biomarker was demonstrated between the PTC and NG groups. After determining the AUC for the tested biomarker, the B-Cat ratio of the area value 0.721 was the strong diagnostic test. CONCLUSIONS: Changes in the plasma B-Cat concentration can be the biomarker of thyroid cancer but it cannot be used for the detection of papillary thyroid carcinoma because of concomitant tumor-like lesions in the thyroid gland. PMID- 26351789 TI - Surgical Treatment Results In Gastroschisis Based On Preterm Delivery Within The 34th Week Of Gestation By Caesarean Section. AB - The aim of the study was to assess the value of the today's appropriate approach, preterm delivery in the 34th week of gestation by Caesarean section and subsequent surgical intervention at the perinatal center, in daily practice of pediatric surgery with regard to early postoperative and mid-term outcome. MATERIAL AND METHODS: Over the time period of 9 years, all consecutive cases diagnosed with gastroschisis at the perinatal center, University Hospital of Magdeburg, were born by Caesarean section within the 34th week of gestation followed by surgical intervention. The registered data were compared with those published by other groups. RESULTS: Overall, there were 19 cases through the investigation period from 01/01/2006 to 12/31/2014. The mean duration of gestation was 237.9 days. The mean birth weight was 2,276 g. In all individuals, a primary closure with no artificial material was achieved. The duration of postoperative artificial respiration was 2.3 days. Oral uptake could be initiated on the 10th postoperative day on average. The mean hospital stay was 37 days. There was no lethality. As complications, postoperative (iv catheter-associated) sepsis occurred in one case and relaparotomy became necessary in a further case because of no possible completion of enteral nutrition by 20 days after primary closure (complication and relaparotomy rate, 10.5% and 5.26%, respectively). CONCLUSIONS: The data indicate that in case of gastroschisis, primary closure can be more frequently achieved by section within the 34th week of gestation. Under the prediction of an optimal neonatological care, the risks of a preterm delivery by a planned section appear to be manageable. PMID- 26351790 TI - Evaluation Of Antioxidant Defense In Patients With Colorectal Carcinoma. AB - Cancers are among the most feared diseases of modern civilization. In Poland, colorectal cancer is one of the tumors with the worst prognosis. The ability to cure is primarily dependent on the stage of the disease at the time of diagnosis. The aim of the study was evaluate antioxidant response in patients with colorectal carcinoma. MATERIAL AND METHODS: Twenty patients (14 men and 6 women) aged 61.9+/- 11.1 years with colorectal cancer were included in the study. Twenty healthy subjects (4 men and 16 women) aged 64 +/- 15.3 years formed the control group. The erythrocyte activities of antioxidant enzymes, superoxide dismutase (SOD), and glutathione peroxidase (GPx), Results. A significant increase of GPx, and SOD (p < 0.05) were seen in patients compared to healthy controls. CONCLUSION: The results indicate that the tested antioxidant enzyme activity of glutathione peroxidase and superoxide dismutase is increased in patients diagnosed with colorectal cancer compared to the control group. PMID- 26351791 TI - Late Band Migration After SAGB. Case Report. AB - Obesity, a major public health issue of the 21st century, is increasingly common in adults and children. No good results of pharmacological treatment of obesity results in rapid development of bariatric surgery, which treats obesity and comorbidities associated. There are many surgical options for treating obesity. Options for surgical management of morbid obesity include restrictive (adjustable gastric banding, vertical band gastroplasty), restrictive/resective (sleeve gastrectomy), restrictive/malabsorptive (Rouxen-Y gastric by-pass, biliopancreatic diversion with duodenal switch) and purely malabsorptive procedures (duodenal switch). Among them, swedish adjustable gastric banding (SAGB) or laparoscopic adjustable gastric banding (LAGB) have been more frequently performed. SAGB is considered to be safe and effective method of weight loss and elimination of diseases associated with obesity. Laparoscopic gastric banding offers the advantages of minimally invasive surgery, adjustability, and reversibility. Despite fewer number of complications than other bariatric operations, patients after SAGB may have unique complications that are characteristic of the SAGB and require special management and treatment. This paper presents a rare case of complete migration of the band into the gastric lumen. PMID- 26351792 TI - De Garengeot's Hernia; Acute Appendicitis In An Incarcerated Femoral Hernia. AB - Acute appendicitis and incarcerated femoral hernia belong to relatively well known surgical diseases with regard to diagnostic workup and treatment. de Garengeot's hernia is an entity involving concurrent occurrence of both the above mentioned problems. This paper presents history of a 58-year old female patient who was diagnosed with this extremely rare syndrome. She presented to the Emergency Room of a hospital in Zyrardow due to painful mass in the right groin region, persisting for approximately 24 hours. De Garengeot's hernia, through combination of two separate surgical entities, is associated with diagnostic difficulties and the therapeutic process occasionally requires unconventional decisions to be taken to improve prognosis. PMID- 26351793 TI - Multifocal Extra-Adrenal Paraganglioma - Case Report. AB - Paraganglioma is a rare neoplasm originating from extra-adrenal pheochromocytes of the sympathetic and parasympathetic nervous system. It is usually benign and the treatment method of choice is a complete resection of the tumour. The authors present a case of 66-year-old female patient with a multifocal benign retroperitoneal paraganglioma, which was completely removed during surgery. PMID- 26351795 TI - Beginings Of The Laparparoscopic Procedures In Poland. PMID- 26351794 TI - Encapsulating Peritoneal Sclerosis - Rare Cause Of Bowel Obstruction. PMID- 26351796 TI - Air pollution: health effects and assessment of exposure levels. PMID- 26351797 TI - Assessment of mycotoxin risk on corn in the Philippines under current and future climate change conditions. AB - This study attempts to assess the risk of mycotoxins (aflatoxins and fumonisins) contamination on corn in the Philippines under current and projected climate change conditions using fuzzy logic methodology based on the published range of temperature and rainfall conditions that favor mycotoxin development. Based on the analysis, projected climatic change will reduce the risk of aflatoxin contamination in the country due to increased rainfall. In the case of fumonisin contamination, most parts of the country are at a very high risk both under current conditions and the projected climate change conditions. PMID- 26351798 TI - A comprehensive review of biomass resources and biofuel production in Nigeria: potential and prospects. AB - The quest for biofuels in Nigeria, no doubt, represents a legitimate ambition. This is so because the focus on biofuel production has assumed a global dimension, and the benefits that may accrue from such effort may turn out to be enormous if the preconditions are adequately satisfied. As a member of the global community, it has become exigent for Nigeria to explore other potential means of bettering her already impoverished economy. Biomass is the major energy source in Nigeria, contributing about 78% of Nigeria's primary energy supply. In this paper, a comprehensive review of the potential of biomass resources and biofuel production in Nigeria is given. The study adopted a desk review of existing literatures on major energy crops produced in Nigeria. A brief description of the current biofuel developmental activities in the country is also given. A variety of biomass resources exist in the country in large quantities with opportunities for expansion. Biomass resources considered include agricultural crops, agricultural crop residues, forestry resources, municipal solid waste, and animal waste. However, the prospects of achieving this giant stride appear not to be feasible in Nigeria. Although the focus on biofuel production may be a worthwhile endeavor in view of Nigeria's development woes, the paper argues that because Nigeria is yet to adequately satisfy the preconditions for such program, the effort may be designed to fail after all. To avoid this, the government must address key areas of concern such as food insecurity, environmental crisis, and blatant corruption in all quarters. It is concluded that given the large availability of biomass resources in Nigeria, there is immense potential for biofuel production from these biomass resources. With the very high potential for biofuel production, the governments as well as private investors are therefore encouraged to take practical steps toward investing in agriculture for the production of energy crops and the establishment of biofuel-processing plants in Nigeria. PMID- 26351799 TI - Climate change and health in the Eastern Mediterranean countries: a systematic review. AB - OBJECTIVES: To summarize the existing knowledge of the impact of climate change on health from previous research in the Eastern Mediterranean region (EMR) and identify knowledge and research gaps. METHODS: Different databases were searched for relevant studies published in the region between 2000 and 2014. The review was limited to studies reporting the impacts of climate change on health or studying associations between meteorological parameters and well-defined human health outcomes. RESULTS: This systematic review of 78 studies identified many knowledge and research gaps. Research linking climate change and health is scarce in the most vulnerable countries of the region. There is limited information regarding how changes in temperature, precipitation and other weather variables might affect the geographic range and incidence of mortality and morbidity from various diseases. Available research has many limitations and shortcomings that arise from inappropriate study designs, poor assessment of exposure and outcomes, questionable sources of data, lack of standardized methods, poor adjustment of confounders, limited geographical area studies, small sample sizes, poor statistical modeling and not testing for possible interactions between exposures. CONCLUSIONS: Research and information on the effect of climate change on health are limited. Longitudinal studies over extended periods of time that investigate the link between climate change and health are needed. There is a need for studies to be expanded to include more countries in the region and to include other environmental, social and economic factors that might affect the spread of the disease. PMID- 26351800 TI - A review of environmental lead exposure and management in Mount Isa, Queensland. AB - The public health leadership and management of lead exposure in a lead mining and smelting community in Mount Isa is an ongoing issue. There exists deficiencies in public health and environmental legal frameworks that regulate lead exposure and management in Mount Isa, Queensland. Although some positive practical measures on lead containment have been implemented, evidence suggests they are currently inadequate. Greater investments in public health leadership at a local and state level are required to address the ongoing issue of lead in Mount Isa. PMID- 26351802 TI - Neuroprotective effects of glucose-dependent insulinotropic polypeptide in Alzheimer's disease. AB - Glucose-dependent insulinotropic polypeptide (GIP) is a member of the incretin hormones and growth factors. Neurons express the GIP receptor, and GIP and its agonists can pass through the blood brain barrier and show remarkable neuroprotective effects by protecting synapse function and numbers, promoting neuronal proliferation, reducing amyloid plaques in the cortex and reducing the chronic inflammation response of the nervous system. Long-acting analogues of GIP that are protease resistant had been developed as a treatment for type 2 diabetes. It has been found that such GIP analogues show good protective effects in animal models of Alzheimer's disease. Novel dual agonist peptides that activate the GIP receptor and another incretin receptor, glucagon-like peptide -1 (GLP-1), are under development that show superior effects in diabetic patients compared to single GLP-1 agonists. The dual agonists also show great promise in treating neurodegenerative disorders, and there are currently several clinical trials ongoing, testing GLP-1 mimetics in people with Alzheimer's or Parkinson's disease. PMID- 26351801 TI - Obesity and public health in the Kingdom of Saudi Arabia. AB - Overweight and obesity are now a global epidemic, with more than one in five people qualifying as obese worldwide. These conditions are accompanied by excessive rates of non-communicable diseases (NCDs) related to overweight, like type 2 diabetes mellitus, hypertension, and cardiovascular diseases. Saudi Arabia, which has become increasingly westernized over the past few decades now has one of the highest prevalence rates of overweight and obesity, even in children. This puts the population at great risk for increased rates of NCD mortality. Competing cultures is partly to blame, as the combination of persisting traditional Saudi cultural practices, modern cultural changes, and economic prosperity has created an obesogenic environment that promotes unhealthy eating, sedentary lifestyles, and weight gain. Overweight and obesity are more prevalent in Saudi women than in Saudi men. Interventions targeting the environment are needed in order to promote greater health through healthy eating decisions and increased physical activity or exercise (especially for women). PMID- 26351803 TI - Correlated overexpression of metadherin and SND1 in glioma cells. AB - Glioma is the most common primary brain tumor with poor prognosis. Effective treatment of glioma remains a big challenge due to complex pathogenic mechanisms. Previous studies have shown that metadherin (MTDH) and its interacting protein staphylococcal nuclease domain containing 1 (SND1) are overexpressed in many solid tumors. To elucidate the role of MDTH and SND1 in the pathogenesis of glioma, we examined the expression of MTDH and SND1 in primary glioma tissues and found that both MTDH and SND1 were highly expressed, with similar expression patterns. Co-expression of MTDH and SND1 was associated with advanced glioma grades. In addition, we detected the interaction between MTDH and SND1 in cultured glioma cell lines. MTDH could promote the expression of p65 and SND1 in glioma cells. However, enhanced SND1 expression by MTDH was abolished by the inhibition of p65. In conclusion, we demonstrated high expression levels MTDH and SND1 in primary glioma tissues. MTDH might promote glioma by inducing SND1 expression through the activation of NF-kappaB pathway. MTDH and SND1 may serve as the indicator of malignancy and prognosis as well as therapeutic targets for patients with glioma. PMID- 26351804 TI - External quality assessment of urine particle identification: a Northern European experience. AB - External quality assessment (EQA) schemes for urinalysis have been provided by Labquality Ltd, the publicly owned EQA service provider in Finland, since the 1980s. In 2014, the scheme on urine particle identification had 329 participating laboratories, out of which 60% from 19 countries were outside Finland. Each of the four annual web-based rounds were distributed with four Sternheimer-stained images from a single patient sample, as viewed both by bright-field and phase contrast optics. Participants reported classified categories either at the basic or at the advanced level. Participating laboratories received assessment of their analytical performance as compared to their peers, including reflections from clinical data and preanalytical detail of the specimen. In general, reporting of basic urine particles succeeded in the eight schemes during the years 2013-2014 as follows: red blood cells 82%-92%, white blood cells 82%-97%, squamous epithelial cells 92%-98%, casts 84%-94%, and small epithelial cells 73%-83% (minimum and maximum of expected or accepted reports). This basic level of differentiation is used in routine laboratory reports, or as verification of results produced by automated instruments. Considerable effort is needed to standardise national procedures and reporting formats, in order to improve the shown figures internationally. Future technologies may help to alleviate limitations created by single digital images. Despite improvements, degenerating cells and casts always exhibit intermediate forms creating disputable classifications. That is why assessment of performance should encompass justified acceptable categories into the assessed outcomes. Preanalytical and clinical detail provide essential added value to morphological findings. PMID- 26351805 TI - Methanol electro-oxidation on platinum modified tungsten carbides in direct methanol fuel cells: a DFT study. AB - In exploration of low-cost electrocatalysts for direct methanol fuel cells (DMFCs), Pt modified tungsten carbide (WC) materials are found to be great potential candidates for decreasing Pt usage whilst exhibiting satisfactory reactivity. In this work, the mechanisms, onset potentials and activity for electrooxidation of methanol were studied on a series of Pt-modified WC catalysts where the bare W-terminated WC(0001) substrate was employed. In the surface energy calculations of a series of Pt-modified WC models, we found that the feasible structures are mono- and bi-layer Pt-modified WCs. The tri-layer Pt modified WC model is not thermodynamically stable where the top layer Pt atoms tend to accumulate and form particles or clusters rather than being dispersed as a layer. We further calculated the mechanisms of methanol oxidation on the feasible models via methanol dehydrogenation to CO involving C-H and O-H bonds dissociating subsequently, and further CO oxidation with the C-O bond association. The onset potentials for the oxidation reactions over the Pt modified WC catalysts were determined thermodynamically by water dissociation to surface OH* species. The activities of these Pt-modified WC catalysts were estimated from the calculated kinetic data. It has been found that the bi-layer Pt-modified WC catalysts may provide a good reactivity and an onset oxidation potential comparable to pure Pt and serve as promising electrocatalysts for DMFCs with a significant decrease in Pt usage. PMID- 26351808 TI - Selecting patients for immune checkpoint inhibition in lung cancer. PMID- 26351810 TI - Chemotherapy-free treatment of acute promyelocytic leukemia. PMID- 26351809 TI - Novel drug targets in acute leukemia. PMID- 26351811 TI - Treatment of intermediate-stage hepatocellular carcinoma. PMID- 26351812 TI - Neoadjuvant therapy in melanoma: the fast track to critical new answers. PMID- 26351813 TI - Lenvatinib/everolimus improves survival better than everolimus alone in metastatic renal cell cancer. PMID- 26351814 TI - Regorafenib in metastatic colorectal cancer: optimal dosing and patient selection recommendations. PMID- 26351815 TI - Hodgkin lymphoma: targeting the tumor microenvironment as a therapeutic strategy. AB - Over the past decade, new biologic insights have revealed the key role of the tumor microenvironment in the pathogenesis of classical Hodgkin lymphoma (cHL). The primary Hodgkin Reed-Sternberg (HRS) tumor cells normally constitute less than 1% of the tumor cellularity in cHL, and are surrounded by an abundant and heterogeneous inflammatory infiltrate. The cross talk between the HRS cells and the cells of the cHL microenvironment sustains tumor growth and survival. An improved understanding of this phenomenon has led to the development of novel antitumor strategies that alter the cHL microenvironment, changing it from protective to cytotoxic. Developing new strategies remains a high priority because--despite the curability of cHL--as many as one-third of advanced-stage patients will relapse after first-line therapy. Furthermore, only half of relapsed patients will obtain long-term disease control through autologous stem cell transplant. In this review, we will provide an overview of the role of the cHL microenvironment in disease biology, the agents currently available or under investigation targeting the cHL microenvironment, and the most promising and innovative treatment platforms being evaluated in clinical trials. PMID- 26351816 TI - Managing acquired resistance in EGFR-mutated non-small cell lung cancer. AB - Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) deliver high response rates with relatively modest toxicity in patients with advanced EGFR-mutated non-small cell lung cancer. Despite this, nearly all tumors eventually develop resistance to first-line therapy. At present, the only standard treatment option for patients with acquired resistance is cytotoxic chemotherapy. In this article, we review the latest research into methods of targeting acquired resistance to EGFR TKI therapy, including third-generation EGFR TKIs that target the T790M resistance mutation and other novel agents in development. PMID- 26351817 TI - Screening for depression and anxiety in patients with storage or voiding dysfunction: A retrospective cohort study predicting outcome of sacral neuromodulation. AB - AIMS: It has been reported that somatic treatment in patients with affective symptoms has a higher risk of failure. The aim was to investigate whether affective symptoms could predict the outcome of sacral neuromodulation (SNM) for lower urinary tract symptoms (LUTS). METHODS: All patients that underwent a SNM evaluation between 2006 and 2013 and filled out a Hospital Anxiety and Depression Score (HADS) before treatment, were included. Chi-square analysis and bivariate logistic regression were used to assess associations and predictive value. RESULTS: Eighty-six patients were included, 65 females and 21 males. Most patients, 66, had overactive bladder syndrome (OAB). The remaining 20 patients suffered from non-obstructive urinary retention (NOR). Thirty-nine OAB patients and 17 NOR patients, had a normal total HADS score before treatment. Significantly more patients showed abnormal HADS-D (P = 0.047) and HADS-A (P = 0.015) scores in the OAB group compared to the NOR group. Success of SNM could not be predicted by the HADS score P = 0.464 (after 1 year P = 0.446). Subsequent analysis revealed that an abnormal HADS score was not related to the occurrence of SNM adverse events. CONCLUSIONS: The present study did not reveal a significant relationship between an abnormal HADS score and failure of the SNM test period in a mixed group of OAB and NOR patients. However, differences between OAB and NOR patients concerning affective symptoms were present. It is known that psychological factors play a role in the severity of LUTS, but they may not predict SNM outcome. Neurourol. Urodynam. 35:1011-1016, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26351818 TI - Comparative Methods for Improving Transepidermal Methylaminolevulinate Delivery: A Randomized Clinical Trial. PMID- 26351819 TI - Pretreatment with diallylsulphide modulates mercury-induced neurotoxicity in male rats. AB - Many studies have reported on the toxicity and related oxidative stress of mercury. Antioxidants play an important role in counteracting metal-induced neurotoxicity under in vivo conditions. In this study, the effect of diallylsulphide (DAS) was evaluated on mercuric chloride induced activities of catalase, superoxide dismutase, glutathione peroxidase and glutathione content in brains of rats. Pretreatment of rats with DAS in the Hg-treated group also inhibited an increase in lipid peroxidation and elevated acetyl cholinesterase and glutathione content. Activities of antioxidant enzymes were also restored concomitantly when compared to the control rats after DAS administration. DAS also caused a decrease in tumor necrosis factor-alpha level which was higher in HgCl2-treated group. The results indicate that DAS augments antioxidant defense with anti-inflammatory response against HgCl2-induced neurotoxicity. The increased level of antioxidant enzymes enhances the antioxidant potential of the organ to reduce oxidative stress. PMID- 26351820 TI - Exogenous hydrogen sulfide promotes C6 glioma cell growth through activation of the p38 MAPK/ERK1/2-COX-2 pathways. AB - Hydrogen sulfide (H2S) participates in multifarious physiological and pathophysiologic progresses of cancer both in vitro and in vivo. We have previously demonstrated that exogenous H2S promoted liver cancer cells proliferation/anti-apoptosis/angiogenesis/migration effects via amplifying the activation of NF-kappaB pathway. However, the effects of H2S on cancer cell proliferation and apoptosis are controversial and remain unclear in C6 glioma cells. The present study investigated the effects of exogenous H2S on cancer cells growth via activating p38 MAPK/ERK1/2-COX-2 pathways in C6 glioma cells. C6 glioma cells were treated with 400 umol/l NaHS (a donor of H2S) for 24 h. The expression levels of phosphorylated (p)-p38 MAPK, total (t)-p38 MAPK, p-ERK1/2, t ERK1/2, cyclooxygenase-2 (COX-2) and caspase-3 were measured by western blotting assay. Cell viability was detected by Cell Counting Kit-8 (CCK-8). Apoptotic cells were observed by Hoechst 33258 staining assay. Cell proliferation was directly detected under fully automatic inverted microscope. Exposure of C6 glioma cells to NaHS resulted in cell proliferation, as evidenced by an increase in cell viability. In addition, NaHS treatment reduced apoptosis, as indicated by the decreased apoptotic percentage and the cleaved caspase-3 expression. Importantly, exposure of the cells to NaHS increased the expression levels of p p38 MAPK, p-ERK1/2 and COX-2. Notably, co-treatment of C6 glioma cells with 400 umol/l NaHS and AOAA (an inhibitor of CBS) largely suppressed the above NaHS induced effects. Combined treatment with NaHS and SB203580 (an inhibitor of p38 MAPK) or PD-98059 (an inhibitor of ERK1/2) resulted in the synergistic reduction of COX-2 expression and increase of caspase-3 expression, a decreased number of apoptotic cells, along with decreased cell viability. Combined treatment with NS 398 (an inhibitor of COX-2) and NaHS also resulted in the synergistic increase of caspase-3, a decreased in the number of apoptotic cells and the decrease in cell viability. The findings of the present study provide novel evidence that p38 MAPK/ERK1/2-COX-2 pathways are involved in NaHS-induced cancer cell proliferation and anti-apoptosis in C6 glioma cells. PMID- 26351821 TI - A Critical Evaluation of the Updated Evidence for Casting for Equinus Deformity in Children with Cerebral Palsy. AB - BACKGROUND AND PURPOSE: Equinus deformity is common in ambulant children with cerebral palsy (CP). Although lower leg casting is frequently used, the physiological basis for casting and effects beyond range of motion (ROM) gains are unclear. This review critically evaluates the updated evidence for casting in the management of ankle equinus in children with CP. METHODS: Comprehensive searches were conducted using electronic databases AMED, MEDLINE, CINAHL, Scopus, PEDro and the Cochrane Database of Systematic Reviews, publication years 2005 2014, in order to identify literature published since an earlier comprehensive systematic review. Only studies evaluating lower leg casting for conservative management of equinus deformity in children with CP were considered. Two independent raters critically appraised studies against the hierarchy of levels of evidence and rigour of study conduct questions proposed by the American Academy of Cerebral Palsy and Developmental Medicine's methodology for systematic review. RESULTS: Four relevant systematic reviews were identified, although these largely concerned earlier literature. Five original studies were included, all demonstrating improvement in dorsiflexion ROM. Combined treatment with botulinum toxin and casting offered greater and/or more sustained ROM gains than botulinum toxin alone in three studies. Effects on gait parameters and motor function were inconsistent. Participation outcomes were not evaluated. Methodological limitations make firm conclusions difficult. CONCLUSIONS: Recent years have offered little progress in the state of evidence for casting in the management of equinus deformity. Casting appears to offer at least short-term improvement in ankle dorsiflexion, although the proposition that this improves function or avoids surgery is not well substantiated. Future research needs to ensure more robust study design and broader evaluation across domains of the International Classification of Functioning, Disability and Health to determine the functional and long-term effect of casting for equinus deformity. Greater knowledge is required of the effect of casting on muscle structure and function in spastic CP. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26351822 TI - Full Characterization of Colloidal Dynamics at Low Peclet Numbers. AB - Although critical in applications, the dynamics of colloidal systems at low Peclet numbers is poorly understood. Here we introduce an optical technique that permits for the first time a complete characterization of this regime through a continuous and independent measurement of both the diffusive and the advective components of a system's dynamics. For the particular example of gravity-driven colloids, we demonstrate experimentally that the hydrodynamic size and the mass density of particulate suspensions can be measured simultaneously. The proven capabilities are of particular interest for studying the spatial and temporal properties of inhomogeneous colloidal systems where aggregation and structural evolution play major roles. PMID- 26351823 TI - Direct Immersion Annealing of Thin Block Copolymer Films. AB - We demonstrate ordering of thin block copolymer (BCP) films via direct immersion annealing (DIA) at enhanced rate leading to stable morphologies. The BCP films are immersed in carefully selected mixtures of good and marginal solvents that can impart enhanced polymer mobility, while inhibiting film dissolution. DIA is compatible with roll-to-roll assembly manufacturing and has distinct advantages over conventional thermal annealing and batch processing solvent-vapor annealing methods. We identify three solvent composition-dependent BCP film ordering regimes in DIA for the weakly interacting polystyrene-poly(methyl methacrylate) (PS-PMMA) system: rapid short-range order, optimal long-range order, and a film instability regime. Kinetic studies in the "optimal long-range order" processing regime as a function of temperature indicate a significant reduction of activation energy for BCP grain growth compared to oven annealing at conventional temperatures. An attractive feature of DIA is its robustness to ordering other BCP (e.g. PS-P2VP) and PS-PMMA systems exhibiting spherical, lamellar and cylindrical ordering. PMID- 26351824 TI - Heterostructured Au/Pd-M (M = Au, Pd, Pt) nanoparticles with compartmentalized composition, morphology, and electrocatalytic activity. AB - The synthesis, processing, and galvanic exchange of three heterostructured nanoparticle systems is described. The surface accessibility and redox potential of a Au/Pd-Ag dumbbell nanoparticle, where a Au/Pd core/shell region, and a silver region make up the domains, was used to prepare the new nanostructures with controlled composition, morphology, and microstructure. Results indicate that the silver domain was particularly susceptible to galvanic displacement, and was exchanged to Au/Pd-M (M = Au, Pd, Pt). Interestingly, the dumbbell morphology remained after exchange, and the silver region was transformed to hollow, parachute, or concentric domains respectively. The morphology and microstructure change was visualized via TEM and HRTEM, and the composition changes were probed via STEM-EDS imaging and XPS. The electrocatalytic activity of the Au/Pd-M towards methanol oxidation was studied, with results indicating that the Au/Pd-Pt nanoparticles had high activity attributed to the porous nature of the platinum domains. PMID- 26351825 TI - Serum creatinine is associated with the prevalence but not disease progression of multiple system atrophy in Chinese population. AB - OBJECTIVES: Oxidative stress is involved in the pathogenesis of multiple system atrophy (MSA). Creatine, which is converted to creatinine, has an anti-oxidative effect. Our aim is to clarify the correlations between creatinine and the occurrence as well as the progression of MSA. METHODS: A total of 115 patients with probable MSA and 115 age- and gender-matched healthy controls were included in the study. The serum creatinine level of all patients and controls were evaluated and compared. RESULTS: The mean age of MSA patients was 58.18 +/- 8.67 years and the mean disease duration was 2.85 +/- 1.71 years. The creatinine level of MSA patients was significantly lower than that of healthy controls (P < 0.0001). The occurrence of MSA was decreased in the highest creatinine quartiles compared with the lowest creatinine quartiles. In a gender-specific analysis, patients with the highest quartiles and second quartiles of creatinine level had decreased occurrence than patients with the lowest quartile in females, but not in males. The serum level of creatinine was not found correlated with the mean rate of annualised changes, neither with other independent factors, such as age, body mass index (BMI), sex, Unified MSA Rating Scale (UMSARS) scores and disease duration at the initial visit in patients with MSA. CONCLUSION: High level of serum creatinine may be associated with a low occurrence of MSA in Chinese population, especially in female. However, serum creatinine does not deteriorate or ameliorate the progression of MSA. PMID- 26351826 TI - Comparison of hydroxyethyl starch colloids with crystalloids for surgical patients: A systematic review and meta-analysis. AB - BACKGROUND: Fluid therapy is one of the most ubiquitous medical therapeutic interventions. There is a debate over whether colloids or crystalloids are better for fluid resuscitation. Recent large trials and meta-analyses suggest no mortality benefit and possible harm with hydroxyethyl starch (HES) use. However, these trials were conducted in critically ill and septic patients and their applicability to perioperative patients has been challenged. OBJECTIVE: We aimed to evaluate the impact of HES use in scheduled and elective surgical patients. DESIGN: Systematic review and meta-analysis of randomised controlled trials (RCTs). ELIGIBILITY CRITERIA: Only RCTs comparing the use of the synthetic colloid HES with any crystalloid in adults undergoing noncardiac surgery (up to 24 h postop) were considered eligible. For each eligible trial, we extracted the outcomes of all-cause mortality within 90 days, length of hospital stay, major infectious complications, acute kidney injury (AKI) and renal replacement therapy (RRT). RESULTS: We identified 1555 citations, selected 90 for full-text evaluation, and identified 13 eligible RCTs. Trials were small (n = 20 to 202) with low event rates. There was a trend to increased mortality with HES within 90 days [13/373 vs. 3/368; risk ratio 2.97; 95% confidence interval (95% CI) 0.96 to 9.19; I = 0%], no difference in AKI and RRT (risk ratio 1.11; 95% CI 0.26 to 4.69; I = 34%), and no difference in major infectious complications (risk ratio 1.19; 95% CI 0.59 to 2.39; I = 0%). Patients resuscitated with HES had a shorter length of hospital stay (mean difference -1.52 days; 95% CI -2.87 to -0.18), although heterogeneity was high (I = 90%). CONCLUSION: This meta-analysis, based on small studies with low event rates, suggests that there are currently insufficient data to identify a difference in outcomes associated with crystalloids and HES in scheduled or elective noncardiac surgery. PMID- 26351827 TI - The use of rocuronium and sugammadex in paediatric renal transplantation: Two case reports. PMID- 26351828 TI - Impact of preoperative fasting times on blood glucose concentration, ketone bodies and acid-base balance in children younger than 36 months: A prospective observational study. AB - BACKGROUND: In contrast to preoperative fasting guidelines in paediatric anaesthesia, actual fasting times are often too long. OBJECTIVE: The objective of this study was to evaluate the effect of preoperative fasting on glucose concentration, ketone bodies and acid-base balance in children. DESIGN: A prospective, noninterventional, clinical observational study. SETTING: A single centre trial, study period from June 2014 to November 2014. PATIENTS: One hundred children aged 0 to 36 months scheduled for elective paediatric surgery. MAIN OUTCOME MEASURES: Patient demographics, fasting times, haemodynamic data, glucose and ketone body concentrations, and acid-base parameters after induction of anaesthesia were documented using a standardised case report form. RESULTS: Mean fasting period was 7.8 +/- 4.5 (3.5 to 20) h, and deviation from guideline (DeltaGL) was 3.3 +/- 3.2 (-2 to 14) h. Linear regression showed a significant correlation between fasting times and ketone bodies, anion gap, base excess, osmolality as well as bicarbonate (for each, P < 0.05), but not glucose or lactate. In children with DeltaGL more than 2 h (54%), ketone bodies, osmolality and anion gap were significantly higher and base excess significantly lower than children with DeltaGL less than 2 h (for each, P < 0.05). CONCLUSION: After prolonged preoperative fasting, children younger than 36 months can present with ketoacidosis and (low) normal blood glucose concentrations. Actual fasting times should be optimised according to existing guidelines. In small infants, deviations from fasting guidelines should be as short as possible and not longer than 2 h. PMID- 26351829 TI - Neck circumference as a predictor of difficult intubation and difficult mask ventilation in morbidly obese patients: A prospective observational study. AB - BACKGROUND: There is conflicting evidence as to whether obesity and neck circumference are predictors of difficult intubation in the surgical population. In addition, the cut-off neck circumference related to difficult intubation has not been clearly identified. OBJECTIVES: The primary study objective was to determine whether neck circumference and obesity were predictors of difficult intubation in morbidly obese surgical patients. Secondary outcomes included difficult mask ventilation. DESIGN: A prospective, noninterventional study. SETTING: Canadian tertiary care surgical centre between October 2012 and August 2013. PATIENTS: A total of 104 morbidly obese surgical patients (BMI >=40 kg m( 2)) were included in the study. Eighty-eight patients were women and 16 were men. Exclusions were known difficult airway and emergency surgery. MAIN OUTCOME MEASURES: The primary outcome of the study was difficult tracheal intubation. An Intubation Difficulty Scale (IDS) was derived using seven parameters and difficult intubation was defined as IDS of at least 5. The secondary outcome was difficult mask ventilation; mask ventilation was graded as easy or difficult (inadequate, desaturation, two-handed or impossible). RESULTS: Univariate analyses showed that difficult intubation was associated with neck circumference, males, BMI more than 50 kg m(-2), American Society of Anesthesiologists (ASA) status and waist circumference, and difficult mask ventilation with neck circumference, males, BMI more than 50 kg m(-2) and thyromental distance. Multiple logistic regression analysis showed that neck circumference more than 42 cm (P = 0.044) and BMI more than 50 kg m(-2) (P = 0.017) were independent predictors of difficult intubation. Male sex (P = 0.004) and BMI more than 50 kg m(-2) (P = 0.031) were independent predictors of difficult mask ventilation. PMID- 26351830 TI - An unusual cause of postoperative airway obstruction: A case report. PMID- 26351831 TI - The effectiveness of platelet supplementation for the reversal of ticagrelor induced inhibition of platelet aggregation: An in-vitro study. AB - BACKGROUND: Management of ticagrelor-induced bleeding is challenging, as no antidote is currently available. Platelet transfusion, usually proposed to reverse antiplatelet drugs, has been suggested to be ineffective but few data are available. OBJECTIVE: To assess the efficacy of platelet supplementation to restore platelet aggregation inhibited by ticagrelor. DESIGN: In vitro study. SETTING: Blood samples were obtained from the French Blood Bank Institute. PARTICIPANTS: Healthy blood donors. INTERVENTIONS: Whole blood from healthy donors was spiked with ticagrelor or aspirin (used as a positive control). MAIN OUTCOME MEASURES: Platelet aggregation was investigated with impedance aggregometry on whole blood [expressed in ohms (V)] and light transmission aggregometry (expressed in %) on platelet-rich plasma using ADP or arachidonic acid as agonists for ticagrelor or aspirin, respectively. Platelet supplementation was defined as the addition of washed platelet suspension increasing at least 60% of whole blood platelet count. RESULTS: Ticagrelor (3.25 mM) inhibited ADP-induced platelet aggregation compared with control either in whole blood (2 vs. 13 V, P < 0.05) or in platelet-rich plasma (15 vs. 75% P < 0.05). Aspirin (25 mM) inhibited arachidonic acid-induced aggregation (1 vs. 7.5 V, P < 0.05 in whole blood and 5 vs. 77.5%, P = 0.01 in platelet-rich plasma). Platelet supplementation completely restored arachidonic acid-induced platelet aggregation in whole blood (10 vs. 1 V, P = 0.008) and platelet-rich plasma (73 vs. 5%, P < 0.01) in aspirin-treated samples, whereas it failed to correct ADP induced aggregation (2 vs. 2 V in whole blood and 13.5 vs. 15% in platelet-rich plasma, P > 0.05) in ticagrelor-treated samples. We also report a case of a ticagrelor-treated patient in whom platelet transfusion failed to restore ADP induced platelet aggregation. CONCLUSION: Platelet supplementation restored platelet aggregation in aspirin-spiked but not in ticagrelor-spiked samples. These results do not support the use of platelet transfusion to reverse the effects of ticagrelor. PMID- 26351832 TI - Reply to: the minimum clinically important difference is fundamental to all clinical trials. PMID- 26351833 TI - Reply to: using the C-MAC videolaryngoscope as a first-line device for out-of hospital emergency intubation. PMID- 26351834 TI - Systemic and alveolar inflammatory response in the dependent and nondependent lung in patients undergoing lung resection surgery. PMID- 26351835 TI - Reply to: systemic and alveolar inflammatory response in the dependent and nondependent lung in patients undergoing lung resection surgery. PMID- 26351836 TI - Reply to: the 'alligator mouth' or 'reflective intubation' manoeuvre? Describing and modifying the same useful technique for difficult intubation. PMID- 26351837 TI - Outcomes of Childhood Asthma and Wheezy Bronchitis. A 50-Year Cohort Study. AB - RATIONALE: Cohort studies suggest that airflow obstruction is established early in life, manifests as childhood asthma and wheezy bronchitis, and continues into early adulthood. Although an association between childhood asthma and chronic obstructive pulmonary disease (COPD) in later life has been demonstrated, it is unclear if childhood wheezy bronchitis is associated with COPD. OBJECTIVES: To investigate whether childhood wheezy bronchitis increases the risk of COPD in the seventh decade. METHODS: A cohort of children recruited in 1964 at age 10 to 15 years, which was followed up in 1989, 1995, and 2001, was followed up again in 2014 when at age 60 to 65 years. Discrete time-to-event and linear mixed effects models were used. MEASUREMENTS AND MAIN RESULTS: FEV1 and FVC were measured. COPD was defined as post-bronchodilator FEV1/FVC <0.7. Childhood wheezing phenotype was related to 1989, 1995, 2001, and 2014 spirometry data. Three hundred thirty subjects, mean age 61 years, were followed up: 38 with childhood asthma; 53 with childhood wheezy bronchitis; and 239 control subjects (of whom 57 developed adulthood-onset wheeze between ages 16 and 46 yr). In adjusted multivariate analyses, childhood asthma was associated with an increased risk of COPD (odds ratio, 6.37; 95% confidence interval, 3.73-10.94), as was childhood wheezy bronchitis (odd ratio 1.81; 95% confidence interval, 1.12-2.91). The COPD risk increased with childhood asthma, and wheezy bronchitis was associated with reduced FEV1 that was evident by the fifth decade and not an accelerated rate of FEV1 decline. In contrast, adulthood-onset wheeze was associated with accelerated FEV1 decline. CONCLUSIONS: Childhood wheezy bronchitis and asthma are associated with an increased risk of COPD and reduced ventilatory function. PMID- 26351839 TI - Metal-Free Catalytic Approach for Allylic C-H Amination Using N-Heterocycles via sp(3) C-H Bond Activation. AB - A versatile metal-free synthesis of allylic N-heterocycles has been developed using a TBAI/TBHP oxidation system. This general protocol could be applied for the C-N bond formation of electron-deficient phthalimides, imidazoles, triazoles, and sulfonamides with cyclic and acylic olefins. The practical use of the method is demonstrated by the amidation of functionalized biologically active substrates. PMID- 26351838 TI - Virtual Training of the Myosignal. AB - OBJECTIVE: To investigate which of three virtual training methods produces the largest learning effects on discrete and continuous myocontrol. The secondary objective was to examine the relation between myocontrol and manual motor control tests. DESIGN: A cohort analytic study. SETTING: University laboratory. PARTICIPANTS: 3 groups of 12 able-bodied participants (N = 36). INTERVENTIONS: Participants trained the control over their myosignals on 3 consecutive days. Training was done with either myosignal feedback on a computer screen, a virtual myoelectric prosthetic hand or a computer game. Participants performed 2 myocontrol tests and 2 manual motor control tests before the first and after the last training session. They were asked to open and close a virtual prosthetic hand on 3 different velocities as a discrete myocontrol test and followed a line with their myosignals for 30 seconds as a continuous myocontrol test. The motor control tests were a pegboard and grip-force test. MAIN OUTCOME MEASURES: Discrete myocontrol test: mean velocities. Continuous myocontrol test: error and error SD. Pegboard test: time to complete. Grip-force test: produced forces. RESULTS: No differences in learning effects on myocontrol were found for the different virtual training methods. Discrete myocontrol ability did not significantly improve as a result of training. Continuous myocontrol ability improved significantly as a result of training, both on average control and variability. All correlations between the motor control and myocontrol test outcome measures were below .50. CONCLUSIONS: Three different virtual training methods showed comparable results when learning myocontrol. Continuous myocontrol was improved by training while discrete myocontrol was not. Myocontrol ability could not be predicted by the manual motor control tests. PMID- 26351840 TI - Reproductive failure in Arabidopsis thaliana under transient carbohydrate limitation: flowers and very young siliques are jettisoned and the meristem is maintained to allow successful resumption of reproductive growth. AB - The impact of transient carbon depletion on reproductive growth in Arabidopsis was investigated by transferring long-photoperiod-grown plants to continuous darkness and returning them to a light-dark cycle. After 2 days of darkness, carbon reserves were depleted in reproductive sinks, and RNA in situ hybridization of marker transcripts showed that carbon starvation responses had been initiated in the meristem, anthers and ovules. Dark treatments of 2 or more days resulted in a bare-segment phenotype on the floral stem, with 23-27 aborted siliques. These resulted from impaired growth of immature siliques and abortion of mature and immature flowers. Depolarization of PIN1 protein and increased DII VENUS expression pointed to rapid collapse of auxin gradients in the meristem and inhibition of primordia initiation. After transfer back to a light-dark cycle, flowers appeared and formed viable siliques and seeds. A similar phenotype was seen after transfer to sub-compensation point irradiance or CO2 . It also appeared in a milder form after a moderate decrease in irradiance and developed spontaneously in short photoperiods. We conclude that Arabidopsis inhibits primordia initiation and aborts flowers and very young siliques in C-limited conditions. This curtails demand, safeguarding meristem function and allowing renewal of reproductive growth when carbon becomes available again. PMID- 26351841 TI - Use of Genome Engineering to Create Patient Specific MLL Translocations in Primary Human Hematopoietic Stem and Progenitor Cells. AB - One of the challenging questions in cancer biology is how a normal cell transforms into a cancer cell. There is strong evidence that specific chromosomal translocations are a key element in this transformation process. Our studies focus on understanding the developmental mechanism by which a normal stem or progenitor cell transforms into leukemia. Here we used engineered nucleases to induce simultaneous specific double strand breaks in the MLL gene and two different known translocation partners (AF4 and AF9), which resulted in specific chromosomal translocations in K562 cells as well as primary hematopoietic stem and progenitor cells (HSPCs). The initiation of a specific MLL translocation in a small number of HSPCs likely mimics the leukemia-initiating event that occurs in patients. In our studies, the creation of specific MLL translocations in CD34+ cells was not sufficient to transform cells in vitro. Rather, a variety of fates was observed for translocation positive cells including cell loss over time, a transient proliferative advantage followed by loss of the clone, or a persistent proliferative advantage. These studies highlight the application of genome engineering tools in primary human HSPCs to induce and prospectively study the consequences of initiating translocation events in leukemia pathogenesis. PMID- 26351842 TI - Locomotion Induced by Spatial Restriction in Adult Drosophila. AB - Drosophila adults display an unwillingness to enter confined spaces but the behaviors induced by spatial restriction in Drosophila are largely unknown. We developed a protocol for high-throughput analysis of locomotion and characterized features of locomotion in a restricted space. We observed intense and persistent locomotion of flies in small circular arenas (diameter 1.27 cm), whereas locomotion was greatly reduced in large circular arenas (diameter 3.81 cm). The increased locomotion induced by spatial restriction was seen in male flies but not female flies, indicating sexual dimorphism of the response to spatial restriction. In large arenas, male flies increased locomotion in arenas previously occupied by male but not female individuals. In small arenas, such pre conditioning had no effect on male flies, which showed intense and persistent locomotion similar to that seen in fresh arenas. During locomotion with spatial restriction, wildtype Canton-S males traveled slower and with less variation in speed than the mutant w1118 carrying a null allele of white gene. In addition, wildtype flies showed a stronger preference for the boundary than the mutant in small arenas. Genetic analysis with a series of crosses revealed that the white gene was not associated with the phenotype of boundary preference in wildtype flies. PMID- 26351844 TI - Biofilm Formation in a Permanent Tracheal Stent Implanted for Twenty-Five Years. PMID- 26351843 TI - Contributions of the Epidermal Growth Factor Receptor to Acquisition of Platinum Resistance in Ovarian Cancer Cells. AB - Acquisition of platinum resistance following first line platinum/taxane therapy is commonly observed in ovarian cancer patients and prevents clinical effectiveness. There are few options to prevent platinum resistance; however, demethylating agents have been shown to resensitize patients to platinum therapy thereby demonstrating that DNA methylation is a critical contributor to the development of platinum resistance. We previously reported the Epidermal Growth Factor Receptor (EGFR) is a novel regulator of DNA methyltransferase (DNMT) activity and DNA methylation. Others have shown that EGFR activation is linked to cisplatin treatment and platinum resistance. We hypothesized that cisplatin induced activation of the EGFR mediates changes in DNA methylation associated with the development of platinum resistance. To investigate this, we evaluated EGFR signaling and DNMT activity after acute cisplatin exposure. We also developed an in vitro model of platinum resistance to examine the effects of EGFR inhibition on acquisition of cisplatin resistance. Acute cisplatin treatment activates the EGFR and downstream signaling pathways, and induces an EGFR mediated increase in DNMT activity. Cisplatin resistant cells also showed increased DNMT activity and global methylation. EGFR inhibition during repeated cisplatin treatments generated cells that were more sensitive to cisplatin and did not develop increases in DNA methylation or DNMT activity compared to controls. These findings suggest that activation of EGFR during platinum treatment contributes to the development of platinum resistance. Furthermore, EGFR inhibition may be an effective strategy at attenuating the development of platinum resistance thereby enhancing the effectiveness of chemotherapeutic treatment in ovarian cancer. PMID- 26351845 TI - Cortical Superficial Siderosis and Risk of Bleeding after Thrombolysis for Ischemic Stroke. AB - BACKGROUND: Cortical superficial siderosis (CSS) is a neuroimaging marker of cerebral amyloid angiopathy and has been associated with a high risk for early subsequent major intracranial hemorrhage (ICH). Therefore, many experts recommend withholding of antithrombotic medication to patients with CSS. In this study, we sought to investigate the prevalence of CSS and the associated risk of ICH in the setting of intravenous thrombolysis (IVT) for ischemic stroke. METHODS: We retrospectively searched the medical documentation system of our primary and tertiary care university clinic for all patients with ischemic stroke that received IVT from 2009 to December 2014. All available imaging data were reviewed in a standardized manner and blinded to any clinical data for the presence of CSS and ICH. CSS was defined as linear signal loss along the cerebral cortex on gradient echo T2*-weighted sequences. A stroke neurologist, who was blinded to the neuroimaging data, extracted the corresponding clinical data including follow up information. RESULTS: We identified 298 patients that received IVT and had undergone brain MRI (mean age 67.6 +/- 12.6 years, 59.4% male). Cerebral MRI was performed in 116 patients (38.9%) before and in 182 patients (61.1%) after IVT (median time from stroke symptom onset to MRI: 1 day; range 0-7 days). Only 3 patients (2 females and 1 male aged 90, 76 and 73 years, respectively) had CSS (1%). All of them had a middle cerebral artery (MCA) stroke with a corresponding vessel occlusion. The 76-year-old female patient had extensive CSS and numerous cerebral microbleeds and received another IVT treatment for recurrent MCA stroke 8 months after the first event. After both IVTs, she had clinically asymptomatic small ICH outside the ischemic infarct and distant from CSS. The 2 other patients had only mild to moderate CSS and did not experience any ICH on postthrombolytic imaging. CONCLUSIONS: The prevalence of CSS in a clinical cohort of stroke patients that received IVT was low and thus does not appear to pose a substantial risk for symptomatic ICH although this may occur in individual patients. However, such analysis also needs to be extended to the very old stroke patients in whom IVT is increasingly used. PMID- 26351846 TI - A Method for Using Player Tracking Data in Basketball to Learn Player Skills and Predict Team Performance. AB - Player tracking data represents a revolutionary new data source for basketball analysis, in which essentially every aspect of a player's performance is tracked and can be analyzed numerically. We suggest a way by which this data set, when coupled with a network-style model of the offense that relates players' skills to the team's success at running different plays, can be used to automatically learn players' skills and predict the performance of untested 5-man lineups in a way that accounts for the interaction between players' respective skill sets. After developing a general analysis procedure, we present as an example a specific implementation of our method using a simplified network model. While player tracking data is not yet available in the public domain, we evaluate our model using simulated data and show that player skills can be accurately inferred by a simple statistical inference scheme. Finally, we use the model to analyze games from the 2011 playoff series between the Memphis Grizzlies and the Oklahoma City Thunder and we show that, even with a very limited data set, the model can consistently describe a player's interactions with a given lineup based only on his performance with a different lineup. PMID- 26351847 TI - Standardizing the Early Identification of Acute Kidney Injury: The NHS England National Patient Safety Alert. AB - Whilst varying standards of care for patients with acute kidney injury (AKI) continue to contribute to poor outcomes, a strong focus on strategies to drive quality improvement is paramount. To this end, a national Patient Safety Alert was issued in June 2014 to all healthcare providers in England entitled 'Standardising the Early Identification of Acute Kidney Injury'. The aim was to embed an automated AKI detection system in the biochemistry laboratories of all acute hospitals. In addition to the direct clinical benefits that may come from earlier and more systematic recognition of AKI, it has also helped position AKI as a patient safety issue and will feed a national AKI registry, the latter a potent tool for future measurement and improvement initiatives. PMID- 26351848 TI - UPR Activation and the Down-Regulation of alpha-Crystallin in Human High Myopia Related Cataract Lens Epithelium. AB - PURPOSE: To investigate the expression of alphaA- and alphaB-crystallin and the unfolded protein response in the lens epithelium of patients with high myopia related cataracts. METHODS AND MATERIALS: The central portion of the human anterior lens capsule together with the adhering epithelial cells, approximately 5 mm in diameter, were harvested and processed within two hours after cataract surgery from high myopia-related (spherical equivalent >=-10.00 diopters) and age related cataract patients or from high myopia but non-cataractous patients (tissue were collected from ocular trauma patients with high myopia and lens trauma). Anterior lens samples from fresh cadaver normal human eyes were used as normal control (collected within 6 hours from death). Real-time PCR was performed to detect the mRNA levels of alpha-crystallins as well as unfolded protein response (UPR)-related GRP78, spliced-XBP1, ATF4 and ATF6. Western blot analysis was used to determine the protein level of alpha-crystallin, GRP78, p-IRE1alpha, p-eIF2alpha and ATF6. RESULTS: In the lens epithelium of the high myopia-related cataract group and the age related cataract group, the mRNA and soluble protein expression of alphaA- and alphaB-crystallin were both decreased; additionally, the protein levels of ATF6, p-eIF2alpha and p-IRE1alpha and the gene expression levels of spliced XBP1, GRP78, ATF6 and ATF4 were greatly increased relative to the normal control. CONCLUSION: These results suggest the significant loss of soluble alpha-crystallin and the activation of the UPR in the lens epithelium of patients with high myopia-related cataract, which may be associated with the cataractogenesis of high myopia-related cataract. PMID- 26351849 TI - Trypanosoma-Cruzi Cross-Reactive Antibodies Longitudinal Follow-Up: A Prospective Observational Study in Hematopoietic Stem Cell Transplantation. AB - Antibodies named TcCRA "Trypanosoma cruzi Cross Reactive Antibodies" were detected in 47% of blood donors from French population unexposed to the parasite. In order to evaluate the passive or active transmissibility of TcCRA and further characterize its role and etiology, we have conducted a study in a cohort of 47 patients who underwent allogeneic Hematopoietic Stem Cell Transplantations (allo HSCT). Donors and recipients were tested for TcCRA prior to transplantation. Recipients were further tested during follow-up after transplantation. Demographical, clinical and biological data were collected. Our primary end-point was to assess the risk of TcCRA acquisition after transplantation. During this initial analysis, we observed no seroconversion in patients receiving cells from TcCRA negative donors (n = 23) but detected seroconversion in 4 out of 24 patients who received hematopoietic stem cells from positive donors. Here, we are discussing possible scenarios to explain TcCRA-immune status in recipient after transplantation. PMID- 26351850 TI - Are High-Severity Fires Burning at Much Higher Rates Recently than Historically in Dry-Forest Landscapes of the Western USA? AB - Dry forests at low elevations in temperate-zone mountains are commonly hypothesized to be at risk of exceptional rates of severe fire from climatic change and land-use effects. Their setting is fire-prone, they have been altered by land-uses, and fire severity may be increasing. However, where fires were excluded, increased fire could also be hypothesized as restorative of historical fire. These competing hypotheses are not well tested, as reference data prior to widespread land-use expansion were insufficient. Moreover, fire-climate projections were lacking for these forests. Here, I used new reference data and records of high-severity fire from 1984-2012 across all dry forests (25.5 million ha) of the western USA to test these hypotheses. I also approximated projected effects of climatic change on high-severity fire in dry forests by applying existing projections. This analysis showed the rate of recent high-severity fire in dry forests is within the range of historical rates, or is too low, overall across dry forests and individually in 42 of 43 analysis regions. Significant upward trends were lacking overall from 1984-2012 for area burned and fraction burned at high severity. Upward trends in area burned at high severity were found in only 4 of 43 analysis regions. Projections for A.D. 2046-2065 showed high severity fire would generally be still operating at, or have been restored to historical rates, although high projections suggest high-severity fire rotations that are too short could ensue in 6 of 43 regions. Programs to generally reduce fire severity in dry forests are not supported and have significant adverse ecological impacts, including reducing habitat for native species dependent on early-successional burned patches and decreasing landscape heterogeneity that confers resilience to climatic change. Some adverse ecological effects of high severity fires are concerns. Managers and communities can improve our ability to live with high-severity fire in dry forests. PMID- 26351851 TI - Resolving Conflicts between Agriculture and the Natural Environment. AB - Agriculture dominates the planet. Yet it has many environmental costs that are unsustainable, especially as global food demand rises. Here, we evaluate ways in which different parts of the world are succeeding in their attempts to resolve conflict between agriculture and wild nature. We envision that coordinated global action in conserving land most sensitive to agricultural activities and policies that internalise the environmental costs of agriculture are needed to deliver a more sustainable future. PMID- 26351852 TI - Combination of Zinc and All-Trans Retinoic Acid Promotes Protection against Listeria monocytogenes Infection. AB - Zinc (Zn) is the second most abundant transition metal after iron. It plays a vital role in living organisms and affects multiple aspects of the immune system. All-trans retinoic acid (atRA) is an isomeric form of the vitamin A or retinol. It possesses the greatest biological activity of Vitamin A. Vitamin A and related retinoids influence many aspects of immunity. In this study, we demonstrated that treatment with a combination of Zn and atRA contributes to host resistance against infection by Listeria monocytogenes. Pretreatment with Zn and atRA enhanced resistance against L. monocytogenes infection in mice and treatment with both Zn and atRA showed a higher protective effect than treatment with either alone. Supplementation with Zn, atRA or their combination decreased the number of L. monocytogenes present in target organs. In vitro, supplementation increased the bacterial uptake by macrophage cells and reduced the replication of L. monocytogenes. Our results suggest that the combination of Zn and atRA has a great bacteriostatic impact on L. monocytogenes and its infection. PMID- 26351853 TI - An Unexpected Diversity of Photoreceptor Classes in the Longfin Squid, Doryteuthis pealeii. AB - Cephalopods are famous for their ability to change color and pattern rapidly for signaling and camouflage. They have keen eyes and remarkable vision, made possible by photoreceptors in their retinas. External to the eyes, photoreceptors also exist in parolfactory vesicles and some light organs, where they function using a rhodopsin protein that is identical to that expressed in the retina. Furthermore, dermal chromatophore organs contain rhodopsin and other components of phototransduction (including retinochrome, a photoisomerase first found in the retina), suggesting that they are photoreceptive. In this study, we used a modified whole-mount immunohistochemical technique to explore rhodopsin and retinochrome expression in a number of tissues and organs in the longfin squid, Doryteuthis pealeii. We found that fin central muscles, hair cells (epithelial primary sensory neurons), arm axial ganglia, and sucker peduncle nerves all express rhodopsin and retinochrome proteins. Our findings indicate that these animals possess an unexpected diversity of extraocular photoreceptors and suggest that extraocular photoreception using visual opsins and visual phototransduction machinery is far more widespread throughout cephalopod tissues than previously recognized. PMID- 26351855 TI - Correction: Context-Dependent Plastic Response during Egg-Laying in a Widespread Newt Species. PMID- 26351854 TI - The Neural Correlates of Shoulder Apprehension: A Functional MRI Study. AB - Although shoulder apprehension is an established clinical finding and is important for the prevention of shoulder dislocation, how this subjective perception is evoked remains unclear. We elucidated the functional neuroplasticity associated with apprehension in patients with recurrent anterior shoulder instability (RSI) using functional magnetic resonance imaging (fMRI). Twelve healthy volunteers and 14 patients with right-sided RSI performed a motor imagery task and a passive shoulder motion task. Brain activity was compared between healthy participants and those with RSI and was correlated with the apprehension intensity reported by participants after each task. Compared to healthy volunteers, participants with RSI exhibited decreased brain activity in the motor network, but increased activity in the hippocampus and amygdala. During the passive motion task, participants with RSI exhibited decreased activity in the left premotor and primary motor/somatosensory areas. Furthermore, brain activity was correlated with apprehension intensity in the left amygdala and left thalamus during the motor imagery task (memory-induced), while a correlation between apprehension intensity and brain activity was found in the left prefrontal cortex during the passive motion task (instability-induced). Our findings provide insight into the pathophysiology of RSI by identifying its associated neural alterations. We elucidated that shoulder apprehension was induced by two different factors, namely instability and memory. PMID- 26351856 TI - Effects of high intensity interval training versus moderate intensity continuous training on the reduction of oxidative stress in type 2 diabetic adult patients: CAT. AB - INTRODUCTION: Oxidative stress is caused by an imbalance between an excessive production of reactive oxygen species and/or a deficiency in the level of endogenous and exogenous antioxidant defenses. The presence of reactive oxygen species in large concentrations and for long periods is associated with the occurrence of various diseases, including type 2 diabetes mellitus. Exercise represents an effective means for the prevention and treatment of type 2 diabetes mellitus, and is also able to reduce long-term oxidative stress levels. High intensity interval training has shown to be an efficient and viable option for type 2 diabetes mellitus control. In turn, high-intensity interval training seems to have positive effects on oxidative stress levels by increasing levels of endogenous antioxidants. OBJECTIVE: To assess the validity and applicability of the results regarding the effectiveness of high-intensity interval training compared to moderate intensity continuous training to reduce oxidative stress in patients with type 2 diabetes mellitus and to answer the following question: In adults with type 2 diabetes mellitus, can the method of high-intensity interval training, compared to moderate intensity continuous training reduce oxidative stress levels? METHODS: We performed a critical analysis of the article "Continuous training vs Interval training in glycemic control and macro and microvascular reactivity in patients with type 2 diabetes". RESULTS: No statistically significant differences were observed in concentrations of superoxide dismutase in any of the experimental groups. Only in the interval group a decrease in malondialdehyde regarding control group and baseline (p<0.05) was observed. In addition, only in the interval group there was an increase in glutathione peroxidase compared to the group of continuous aerobic training and baseline (p<0.05). Nitric oxide showed a significant increase regarding the control, continuous aerobic group and baseline (p<0.05) in the interval training group. CONCLUSIONS: Despite the fact that both training groups show improvements over markers of lipid profile and fitness, high intensity interval training has shown to be more effective in the normalization of oxidative stress, impacting positively on the concentration of pro-oxidant markers and antioxidants. PMID- 26351857 TI - Dietary Fish Oil Inhibits Pro-Inflammatory and ER Stress Signalling Pathways in the Liver of Sows during Lactation. AB - Lactating sows have been shown to develop typical signs of an inflammatory condition in the liver during the transition from pregnancy to lactation. Hepatic inflammation is considered critical due to the induction of an acute phase response and the activation of stress signaling pathways like the endoplasmic reticulum (ER) stress-induced unfolded protein response (UPR), both of which impair animal's health and performance. Whether ER stress-induced UPR is also activated in the liver of lactating sows and whether dietary fish oil as a source of anti-inflammatory effects n-3 PUFA is able to attenuate hepatic inflammation and ER stress-induced UPR in the liver of sows is currently unknown. Based on this, two experiments with lactating sows were performed. The first experiment revealed that ER stress-induced UPR occurs also in the liver of sows during lactation. This was evident from the up-regulation of a set of genes regulated by the UPR and numerically increased phosphorylation of the ER stress-transducer PERK and PERK-mediated phosphorylation of eIF2alpha and IkappaB. The second experiment showed that fish oil inhibits ER stress-induced UPR in the liver of lactating sows. This was demonstrated by decreased mRNA levels of a number of UPR regulated genes and reduced phosphorylation of PERK and PERK-mediated phosphorylation of eIF2alpha and IkappaB in the liver of the fish oil group. The mRNA levels of various nuclear factor-kappaB-regulated genes encoding inflammatory mediators and acute phase proteins in the liver of lactating sows were also reduced in the fish oil group. In line with this, the plasma levels of acute phase proteins were reduced in the fish oil group, although differences to the control group were not significant. In conclusion, ER stress-induced UPR is present in the liver of lactating sows and fish oil is able to inhibit inflammatory signaling pathways and ER stress-induced UPR in the liver. PMID- 26351859 TI - Total Structure and Electronic Structure Analysis of Doped Thiolated Silver [MAg24(SR)18](2-) (M = Pd, Pt) Clusters. AB - With the incorporation of Pd or Pt atoms, thiolated Ag-rich 25-metal-atom nanoclusters were successfully prepared and structurally characterized for the first time. With a composition of [PdAg24(SR)18](2-) or [PtAg24(SR)18](2-), the obtained 25-metal-atom nanoclusters have a metal framework structure similar to that of widely investigated Au25(SR)18. In both clusters, a M@Ag12 (M = Pd, Pt) core is capped by six distorted dimeric -RS-Ag-SR-Ag-SR- units. However, the silver-thiolate overlayer gives rise to a geometric chirality at variance to Au25(SR)18. The effect of doping on the electronic structure was studied through measured optical absorption spectra and ab initio analysis. This work demonstrates that modulating electronic structures by transition-metal doping is expected to provide effective means to manipulate electronic, optical, chemical, and catalytic properties of thiolated noble metal nanoclusters. PMID- 26351858 TI - ENLIST 1: An International Multi-centre Cross-sectional Study of the Clinical Features of Erythema Nodosum Leprosum. AB - Erythema nodosum leprosum (ENL) is a severe multisystem immune mediated complication of borderline lepromatous leprosy and lepromatous leprosy. ENL is associated with skin lesions, neuritis, arthritis, dactylitis, eye inflammation, osteitis, orchitis, lymphadenitis and nephritis. The treatment of ENL requires immunosuppression, which is often required for prolonged periods of time and may lead to serious adverse effects. ENL and its treatment is associated with increased mortality and economic hardship. Improved, evidence-based treatments for ENL are needed; however, defining the severity of ENL and outcome measures for treatment studies is difficult because of the multiple organ systems involved. A cross-sectional study was performed, by the members of the Erythema Nodosum Leprosum International STudy (ENLIST) Group, of patients with ENL attending seven leprosy referral centres in Brazil, Ethiopia, India, Nepal, the Philippines and the United Kingdom. We systematically documented the clinical features and type of ENL, its severity and the drugs used to treat it. Patients with chronic ENL were more likely to be assessed as having severe ENL. Pain, the most frequent symptom, assessed using a semi-quantitative scale was significantly worse in individuals with "severe" ENL. Our findings will determine the items to be included in a severity scale of ENL which we are developing and validating. The study also provides data on the clinical features of ENL, which can be incorporated into a definition of ENL and used for outcome measures in treatment studies. PMID- 26351860 TI - Molecular Basis for Stellatic Acid Biosynthesis: A Genome Mining Approach for Discovery of Sesterterpene Synthases. AB - The search for a new sesterterpene synthase in the genome of Emericella variecolor, which reportedly produces diverse sesterterpenoids, is described. One gene product (a chimeric protein with prenyltransferase and terpene cyclase domains) led to the synthesis of a novel tricyclic sesterterpene, stellata-2,6,19 triene (1), from DMAPP and IPP, and the hydrocarbon was further transformed into stellatic acid (2) by cytochrome P450 monooxygenase encoded by the gene adjacent to the sesterterpene synthase gene. PMID- 26351861 TI - 17th International Conference on Human Retroviruses: HTLV and Related Viruses. PMID- 26351862 TI - Neural Correlates of Visual Short-term Memory Dissociate between Fragile and Working Memory Representations. AB - Evidence is accumulating that the classic two-stage model of visual STM (VSTM), comprising iconic memory (IM) and visual working memory (WM), is incomplete. A third memory stage, termed fragile VSTM (FM), seems to exist in between IM and WM [Vandenbroucke, A. R. E., Sligte, I. G., & Lamme, V. A. F. Manipulations of attention dissociate fragile visual STM from visual working memory. Neuropsychologia, 49, 1559-1568, 2011; Sligte, I. G., Scholte, H. S., & Lamme, V. A. F. Are there multiple visual STM stores? PLoS One, 3, e1699, 2008]. Although FM can be distinguished from IM using behavioral and fMRI methods, the question remains whether FM is a weak expression of WM or a separate form of memory with its own neural signature. Here, we tested whether FM and WM in humans are supported by dissociable time-frequency features of EEG recordings. Participants performed a partial-report change detection task, from which individual differences in FM and WM capacity were estimated. These individual FM and WM capacities were correlated with time-frequency characteristics of the EEG signal before and during encoding and maintenance of the memory display. FM capacity showed negative alpha correlations over peri-occipital electrodes, whereas WM capacity was positively related, suggesting increased visual processing (lower alpha) to be related to FM capacity. Furthermore, FM capacity correlated with an increase in theta power over central electrodes during preparation and processing of the memory display, whereas WM did not. In addition to a difference in visual processing characteristics, a positive relation between gamma power and FM capacity was observed during both preparation and maintenance periods of the task. On the other hand, we observed that theta-gamma coupling was negatively correlated with FM capacity, whereas it was slightly positively correlated with WM. These data show clear differences in the neural substrates of FM versus WM and suggest that FM depends more on visual processing mechanisms compared with WM. This study thus provides novel evidence for a dissociation between different stages in VSTM. PMID- 26351863 TI - The Basis for Language Acquisition: Congenitally Deaf Infants Discriminate Vowel Length in the First Months after Cochlear Implantation. AB - One main incentive for supplying hearing impaired children with a cochlear implant is the prospect of oral language acquisition. Only scarce knowledge exists, however, of what congenitally deaf children actually perceive when receiving their first auditory input, and specifically what speech-relevant features they are able to extract from the new modality. We therefore presented congenitally deaf infants and young children implanted before the age of 4 years with an oddball paradigm of long and short vowel variants of the syllable /ba/. We measured the EEG in regular intervals to study their discriminative ability starting with the first activation of the implant up to 8 months later. We were thus able to time-track the emerging ability to differentiate one of the most basic linguistic features that bears semantic differentiation and helps in word segmentation, namely, vowel length. Results show that already 2 months after the first auditory input, but not directly after implant activation, these early implanted children differentiate between long and short syllables. Surprisingly, after only 4 months of hearing experience, the ERPs have reached the same properties as those of the normal hearing control group, demonstrating the plasticity of the brain with respect to the new modality. We thus show that a simple but linguistically highly relevant feature such as vowel length reaches age-appropriate electrophysiological levels as fast as 4 months after the first acoustic stimulation, providing an important basis for further language acquisition. PMID- 26351864 TI - Prefrontal Engagement and Reduced Default Network Suppression Co-occur and Are Dynamically Coupled in Older Adults: The Default-Executive Coupling Hypothesis of Aging. AB - Reduced executive control is a hallmark of neurocognitive aging. Poor modulation of lateral pFC activity in the context of increasing task challenge in old adults and a "failure to deactivate" the default network during cognitive control tasks have been observed. Whether these two patterns represent discrete mechanisms of neurocognitive aging or interact into older adulthood remains unknown. We examined whether altered pFC and default network dynamics co-occur during goal directed planning over increasing levels of difficulty during performance on the Tower of London task. We used fMRI to investigate task- and age-related changes in brain activation and functional connectivity across four levels of task challenge. Frontoparietal executive control regions were activated and default network regions were suppressed during planning relative to counting performance in both groups. Older adults, unlike young, failed to modulate brain activity in executive control and default regions as planning demands increased. Critically, functional connectivity analyses revealed bilateral dorsolateral pFC coupling in young adults and dorsolateral pFC to default coupling in older adults with increased planning complexity. We propose a default-executive coupling hypothesis of aging. First, this hypothesis suggests that failure to modulate control and default network activity in response to increasing task challenge are linked in older adulthood. Second, functional brain changes involve greater coupling of lateral pFC and the default network as cognitive control demands increase in older adults. We speculate that these changes reflect an adaptive shift in cognitive approach as older adults come to rely more upon stored representations to support goal-directed task performance. PMID- 26351865 TI - Cuminaldehyde as the Major Component of Cuminum cyminum, a Natural Aldehyde with Inhibitory Effect on Alpha-Synuclein Fibrillation and Cytotoxicity. AB - Fibrillation of alpha-synuclein (alpha-SN) is a critical process in the pathophysiology of several neurodegenerative diseases, especially Parkinson's disease. Application of bioactive inhibitory compounds from herbal extracts is a potential therapeutic approach for this cytotoxic process. Here, we investigated the inhibitory effects of the Iranian Cuminum cyminum essential oil on the fibrillation of alpha-SN. Analysis of different fractions from the total extract identified cuminaldehyde as the active compound involved in the antifibrillation activity. In comparison with baicalein, a well-known inhibitor of alpha-SN fibrillation, cuminaldehyde showed the same activity in some aspects and a different activity on other parameters influencing alpha-SN fibrillation. The presence of spermidine, an alpha-SN fibrillation inducer, dominantly enforced the inhibitory effects of cuminaldehyde even more intensively than baicalein. Furthermore, the results from experiments using preformed fibrils and monobromobimane-labeled monomeric protein also suggest that cuminaldehyde prevents alpha-SN fibrillation even in the presence of seeds, having no disaggregating impact on the preformed fibrils. Structural studies showed that cuminaldehyde stalls protein assembly into beta-structural fibrils, which might be achieved by the interaction with amine groups through its aldehyde group as a Schiff base reaction. This assumption was supported by FITC labeling efficiency assay. In addition, cytotoxicity assays on PC12 cells showed that cuminaldehyde is a nontoxic compound, treatment with cuminaldehyde throughout alpha-SN fibrillation showed no toxic effects on the cells. Taken together, these results show for the first time that the small abundant natural compound, cuminaldehyde, can modulate alpha-SN fibrillation. Hence, suggesting that such natural active aldehyde could have potential therapeutic applications. PMID- 26351867 TI - Fabrication of conductive polymer nanofibers through SWNT supramolecular functionalization and aqueous solution processing. AB - Polymeric thin films and nanostructured composites with excellent electrical properties are required for the development of advanced optoelectronic devices, flexible electronics, wearable sensors, and tissue engineering scaffolds. Because most polymers available for fabrication are insulating, one of the biggest challenges remains the preparation of inexpensive polymer composites with good electrical conductivity. Among the nanomaterials used to enhance composite performance, single walled carbon nanotubes (SWNTs) are ideal due to their unique physical and electrical properties. Yet, a barrier to their widespread application is that they do not readily disperse in solvents traditionally used for polymer processing. In this study, we employed supramolecular functionalization of SWNTs with a conjugated polyelectrolyte as a simple approach to produce stable aqueous nanotube suspensions, that could be effortlessly blended with the polymer poly(ethyleneoxide) (PEO). The homogeneous SWNT:PEO mixtures were used to fabricate conductive thin films and nanofibers with improved conductivities through drop casting and electrospinning. The physical characterization of electrospun nanofibers through Raman spectroscopy and SEM revealed that the SWNTs were uniformly incorporated throughout the composites. The electrical characterization of SWNT:PEO thin films allowed us to assess their conductivity and establish a percolation threshold of 0.1 wt% SWNT. Similarly, measurement of the nanofiber conductivity showed that the electrospinning process improved the contact between nanotube complexes, resulting in conductivities in the S m(-1) range with much lower weight loading of SWNTs than their thin film counterparts. The methods reported for the fabrication of conductive nanofibers are simple, inexpensive, and enable SWNT processing in aqueous solutions, and offer great potential for nanofiber use in applications involving flexible electronics, sensing devices, and tissue engineering scaffolds. PMID- 26351866 TI - Retinoic acid-incorporated glycol chitosan nanoparticles inhibit the expression of Ezh2 in U118 and U138 human glioma cells. AB - At present, one of the most life threatening types of adult brain tumor is glioblastoma multiforme (GBM). The molecular mechanism underlying the progression of GBM remains to be fully elucidated. The modern method of clinical treatment has only improved the average survival rates of a newly diagnosed patients with GBM by ~15 months. Therefore, the discovery of novel molecules, which are involved in glioma inhibition is required. In the present study, U118 and U138 human glioma cells were transfected with all-trans retinoic acid (RA) incorporated glycol chitosan (GC) nanoparticles.An MTT assay was used for the analysis of cell proliferation and flow cytometric analysis and ssDNA detection assays were performed for the determination of induction of cell apoptosis. Cell cycle distribution was analyzed by flow cytometry. Exposure of the U118 and U138 human glioma cells to the RA-incorporated GC nanoparticles for 24 h resulted in a concentration-dependent inhibition of cell proliferation. Among the range of experimental RA concentrations, the minimum effective treatment concentration was 10 uM, with a half maximal inhibitory concentration of 25 uM. The results also demonstrated that RA transfection resulted in the inhibition of cell proliferation, inhibition of the expression of Ezh2, and apoptosis through the mitochondrial signaling pathway by a decrease in membrane potential, the release of cytochrome c, and cell cycle arrest in the G0/G1 phase. PMID- 26351868 TI - Posttraumatic Hydrocephalus after Decompressive Craniectomy in 126 Patients with Severe Traumatic Brain Injury. AB - OBJECTIVE: Severe traumatic brain injuries (TBIs) occur frequently. In some of these patients decompressive craniectomy (DC) must be performed. Posttraumatic hydrocephalus (PTH) can develop after TBI further damaging the brain. DC is considered to be one of the causes of PTH. This study defines the incidence of PTH in TBI patients who underwent DC and tries to determine associated factors. MATERIALS AND METHODS: We conducted a retrospective study (2009-2013) that included 126 patients with severe TBI and DC. The collected data were demographics, the craniectomy size, the presence or absence of hydrocephalus, the need for changing the opening pressure of the valve of the cerebrospinal fluid (CSF) shunt or replacing all or parts of the CSF shunt, and the interval between cranioplasty and shunt placement. We excluded patients with additional intraventricular hemorrhage and those with bilateral or bifrontal DC. RESULTS: Ten of the 126 patients (7.9%) developed PTH and were treated with a CSF shunt. There was no statistical correlation between development of PTH and age or sex, but a statistically significant correlation between development of PTH and the size of DC. CONCLUSION: Our study suggests that PTH development is multifactorial and shows that PTH is not that rare. We showed a correlation between craniectomy size and the incidence of PTH. PMID- 26351869 TI - Treatment of Central Deafferentation and Trigeminal Neuropathic Pain by Motor Cortex Stimulation: Report of a Series of 20 Patients. AB - OBJECTIVE: Motor cortex stimulation (MCS) is an alternative treatment modality for central neuropathic pain, if conservative treatment failed. Study aim was outcome assessment after MCS. MATERIAL AND METHODS: This study is a retrospective case series review of patients who had undergone MCS for central pain (n = 8), deafferentation pain (n = 3) and neuropathic trigeminal pain (n = 9) between April 2001 and May 2011. In all patients, four contact-paddle electrodes were placed in the epidural space overlying the motor cortex via burr hole trepanation under local anesthesia. The follow-up period was 6 months to 6 years. Pain control was assessed by the visual analog scale (VAS). RESULTS: A total of 22 patients (11 men, 11 women) were treated; after trial stimulation two male patients were excluded for incompliance reasons. The mean patient age was 59.8 years (range: 31-79 years). In the central pain group, three patients reported complete, and four patients satisfactory pain control. In the trigeminal neuropathic pain group, seven patients reported complete, and two patients satisfactory pain control. In the deafferentation pain group, one patient reported complete, and two patients satisfactory pain control. None of the patients showed new neurologic deficits after the MCS. CONCLUSIONS: MCS is an effective treatment modality for central neuropathic pain and trigeminal pain with low morbidity and mortality. Future studies are necessary to evaluate and optimize this treatment option in more detail. PMID- 26351870 TI - Efficacy, Security, and Manageability of Gelified Hemostatic Matrix in Bleeding Control during Thoracic and Lumbar Spine Surgery: FloSeal versus Surgiflo. AB - INTRODUCTION: Accurate hemostasis in surgical practice is critical. The need for optimal atraumatic hemostasis has become compelling in neurosurgery. A simple and safe gelified hemostatic matrix is often used. This prospective study evaluates two different hemostatics, FloSeal (Baxter Healthcare, Deerfield, Illinois, United States) and Surgiflo (Ethicon, Somerville, New Jersey, United States), for bleeding control during spine surgery, considering their efficacy, safety, and ease of use. MATERIALS AND METHODS: From January 2012 to December 2013, we recruited 149 patients. Inclusion criteria were age between 25 and 80 years, diagnosis of degenerative or traumatic pathology of the lumbar or thoracolumbar spine, and persistent bleeding not responding to standard hemostatic techniques. All patients underwent laminectomy or laminoarthrectomy, with exposure of the perivertebral venous plexus. Our aim was to stop the bleeding completely in the operative field by application of hemostatic gel. All patients were evaluated during the follow-up period with a clinical and neurologic examination. All patients underwent a computed tomography scan 3 months after the intervention. RESULTS: We included 149 patients in our study: 98 men and 51 women. Overall, 92 patients were affected by a degenerative condition and 57 by traumatic pathology. A total of 42 patients had anticoagulant and/or antiaggregant therapy preoperatively. In all cases, massive bleeding originated from the epidural venous plexus. FloSeal was used in 86 cases and Surgiflo in 63. A complete hemostasis was achieved in all patients within 3 minutes, 30 seconds and 7 minutes (FloSeal, 5 minutes, 35 seconds +/- 52 seconds; Surgiflo, 5 minutes, 32 seconds +/- 54 seconds). Statistical analysis did not show any association between coagulation time and hemostatics, age, sex, and the pathology treated. Previous therapy with antiaggregants and/or anticoagulants determined a slight increase in the time of hemostasis without any statistical differences. The clinical and radiological follow-up showed no evidence of postsurgical hematomas. CONCLUSIONS: Comparative analysis of the two products did not show any relevant differences in terms of efficacy and ease of use or their effectiveness in bleeding control. Their use was valid even in patients who used antiaggregant/anticoagulant drugs preoperatively. Both FloSeal and Surgiflo can be considered good choices for controlling bleeding in spinal surgery. PMID- 26351871 TI - An Interlaminotomy New Zealand White Rabbit Model to Evaluate Novel Epidural Strategies. AB - OBJECTIVE: The New Zealand White (NZW) rabbit model is an established animal model for examining surgical methods to prevent epidural scar formation after spine surgery. As most approaches include complete laminectomy of the rabbit vertebra, this procedure is associated with high morbidity and mortality rates. We examined a less invasive technique, the microsurgical interlaminotomy, for testing epidural substance application in the rabbit spine. METHODS: Surgery was performed in the cadaver rabbit spine to evaluate the approach before performing it in NZW rabbits. All surgical procedures were performed under an operation microscope. Female rabbits with a mean weight of 4770 g +/- 240 g were used. Neurologic symptoms were analyzed based on predefined scores. After resection of the spinal process, the caudal part of the upper lamina was resected using a drill and a 1-mm Kerrison punch. The yellow ligament was resected resulting in a dural exposure of ~ 5 * 10 mm. RESULTS: Eight pilot interlaminotomies were performed on three cadaveric spines to establish the surgical approach. Twenty one NZW rabbits were then operated on using the interlaminotomy model. Three rabbits (14.3%) died during surgery due to anesthesia-related complications. Two rabbits (9.5%) showed partial paresis of the lower extremities and one (4.8%) a complete paraplegia. The remaining 15 rabbits (71.4%) had an uneventful recovery without neurologic symptoms. The mean surgical duration was 88 +/- 28 minutes. CONCLUSION: The rabbit interlaminotomy model is associated with few neurologic deficits and a relatively short operating time. PMID- 26351872 TI - Surgical Treatment of Severe Traumatic Brain Injury in Switzerland: Results from a Multicenter Study. AB - OBJECTIVE: Since the introduction of modern surgical techniques and monitoring tools for the treatment of severe traumatic brain injury (TBI) in Switzerland, standardized nationwide operative procedures are still lacking. This study aimed to assess surgical management and monitoring strategies in patients admitted throughout Switzerland with severe TBI. METHODS: Demographic, clinical, and radiologic data from a prospective national cohort study on severe brain-injured patients (Patient-relevant Endpoints after Brain Injury from Traumatic Accidents [PEBITA]) were collected during a 3-year period. This study evaluated patients admitted to 7 of the 11 trauma centers included in PEBITA. We retrospectively analyzed surgery-related computed tomography (CT) findings prior to and after treatment, intracranial pressure (ICP) monitoring, size and technical features of craniotomy, as well as surgical complications. ResULTS: This study included 353 of the 921 patients enrolled in PEBITA who underwent surgical treatment for severe TBI. At admission, acute subdural hematoma was the most frequent focal lesion diagnosed (n = 154 [44%]), followed by epidural hematoma (n = 96 [27%]) and intracerebral hematoma (n = 84 [24%]). A total of 198 patients (61%) presented with midline shift. Clinical deterioration in terms of Glasgow Coma Scale scores or intractable ICP values as an indication for surgical evacuation or decompression were documented in 20% and 6%, respectively. A total of 97 (27.5%) only received a catheter/probe for ICP monitoring. Surgical procedures to treat a focal lesion or decompress the cerebrum were performed in 256 patients (72.5%). Of the 290 surgical procedures (excluding ICP probe implantation), craniotomy (137 [47.2%]) or decompressive craniectomy (133 [45.9%]) were performed most frequently. The mean size of craniectomy in terms of maximal linear width on the CT axial slice was 8.4 +/- 2.9 cm. Intraoperative ICP monitoring was reported in 61% of the interventions. Significant intraoperative brain swelling was documented in 50.6% of the procedures. Surgery-related complications occurred in 89 cases (32%). CONCLUSION: This study highlights the lack of standardized and systematic documentation of technical aspects of surgical treatment of patients presenting with severe TBI in Switzerland. Technical strategies such as size of craniectomy and the use of perioperative ICP measurement were not documented in a standardized manner. A prospective systematic surgical documentation system might contribute to future formulation of recommendations for the surgical treatment of patients presenting with severe TBI in Switzerland. PMID- 26351873 TI - Cerebral Nitinol Stenting in Progressive Stroke and in Crescendo TIAs. AB - BACKGROUND: Acute ischemic stroke (AIS) is the third leading cause of death. Arterial stenosis is a common cause of stroke, with a high risk of recurrent stroke. Treatment guidelines for AIS and transient ischemic attack (TIA) are still under debate. Treatment guidelines for progressive stroke or crescendo TIAs do not exist. Percutaneous transluminal angioplasty and stenting (PTAS) is an increasingly attractive treatment option, whose efficacy is yet to be proven. However, stent placement poses both short- and long-term risks such as immediate ischemic events, in-stent stenosis, and stent breakage. Thus the choice of stent type is critical. We report our experience with the LEO + (Balt Extrusion, Montmorency, France) nitinol flexible self-expanding stent for the treatment of progressive cerebrovascular accident or crescendo TIAs. METHODS: Twelve patients, presenting with a clinical picture of a crescendo TIA or progressive stroke in evolution not halted by optimal medical care, were treated. Patients had a corresponding major cerebral arterial narrowing and evidence of cerebral infarction on imaging. Patients were followed clinically and radiographically. RESULTS: Twelve patients 17 to 80 years of age were treated during the study period (20 months). Sixteen nitinol flexible self-expandable stents (LEO +) were placed. All patients showed moderate to substantial improvement in neurologic functions after the procedure. CONCLUSION: PTAS should be considered a treatment option in case of progressive stroke or crescendo TIAs coupled with appropriate anatomical findings. This may allow for a substantial improvement in functional and neurologic status. PMID- 26351874 TI - N-acetyl-S-(p-chlorophenylcarbamoyl)cysteine induces mitochondrial-mediated apoptosis and suppresses migration in melanoma cells. AB - We previously reported that N-acetyl-S-(p-chlorophenylcarbamoyl)cysteine (NACC) induces apoptosis in human melanoma UACC-62 cells. In the present study, the molecular mechanism of NACC-induced apoptosis in melanoma cells was investigated. Briefly, the apoptosis triggered by NACC was confirmed in UACC-62 cells for shorter treatment periods. Increased activities of caspase-3 and caspase-9 but not caspase-8 were observed in the cell lysates. Western blotting showed that the pro-apoptotic protein Bax was upregulated and the anti-apoptotic protein Mcl-1 was downregulated and cytochrome c (Cyto c) was released into the cytosol. Flow cytometric analysis demonstrated that NACC induced significant mitochondrial membrane potential disruption. Significant increases in the generation of reactive oxygen species (ROS) and cytosolic calcium elevation were also observed. However, opening of the mitochondrial permeability transition pore which could be involved in Cyto c leakage from mitochondria was found to be unaffected by NACC. Taken together, all the results presented in this study including apoptotic induction, activation of the caspase-3 and -9 cascade, upregulation of Bax, downregulation of Mcl-1, Cyto c release from the mitochondria, mitochondrial membrane potential depletion, ROS production and cytosolic calcium elevation demonstrated that NACC triggered apoptosis in the UACC-62 cells via the mitochondrial-dependent pathway. Melanoma is well-known as an aggressive and highly metastatic disease. In this study, we also investigated the effects of NACC on the migration of UACC-62 cells using the xCELLigence system. The results revealed that in vitro NACC is capable of inhibiting the migration of melanoma cells. PMID- 26351875 TI - Decreased 13N-labeled ammonia uptake in the ipsilateral and contralateral hemispheres following carotid endarterectomy. AB - Carotid artery plaques are a leading cause of ischemic stroke, and carotid endarterectomy (CEA) is one of the major treatment approaches for this disease. Changes in cerebral metabolism following CEA remain unclear. The present study aimed to evaluate the effect of cerebral ammonia metabolism following CEA using 13N-labeled ammonia positron emission tomography (PET) in humans. A total of 20 patients were enrolled in the present study, with a mean age of 59.5 years, comprising 16 males and four females. Of these patients, eight underwent right CEA and 12 underwent left CEA. The rate of carotid artery stenosis was between 50 69% in six of the patients, between 70-99% in 11 of the patients and was at 100% (thrombosis) in three of the patients, measured by computerised tomography digital subtraction angiography prior to CEA. 13N-labeled ammonia (137 MBq) PET scanning was performed prior and subsequent to CEA surgery for each patient. The first ammonia PET scan was performed 1 day prior to CEA, while the second PET scan was performed 1-4 weeks following CEA. Following injection of 13N-labeled ammonia, static PET was acquired for 10 min. The region of interest (ROI), covering the major cerebral hemisphere, was selected and ammonia uptake in the ROI was determined in the ipsilateral and contralateral hemispheres. No hyperperfusion syndrome was observed in the patients subsequent to CEA. No significant change in cerebral hemisphere ammonia uptake was observed between the ipsilateral and contralateral hemispheres prior to (ratio =0.98; P>0.01) or following (ratio =1.09; P>0.01) CEA. Ammonia uptake in the ipsilateral and contralateral hemispheres was significantly reduced to 23.2 and 23.5%, respectively, following CEA. Using 13N-labeled ammonia PET to evaluate cerebral ammonia metabolism following CEA in patients with severe carotid artery stenosis, the present study demonstrated that uptake of ammonia in the ipsilateral and contralateral hemispheres was significantly reduced. PMID- 26351877 TI - Curcumin inhibits cell proliferation and induces apoptosis of human non-small cell lung cancer cells through the upregulation of miR-192-5p and suppression of PI3K/Akt signaling pathway. AB - Curcumin is the main active ingredient extracted from the traditional Chinese medicine, turmeric, which acts against non-small cell lung cancer cell (NSCLC), lowers blood pressure, is anti-inflammatory, choleretic, and exerts anti-oxidant effects, without any obvious toxicity in the long term. The aim of the present study was to investigate whether the anticancer effect of curcumin inhibited cell proliferation and induced apoptosis of human NSCLC through the upregulation of microRNA-192-5p (miR-192-5p) and suppression of the PI3K/Akt signaling pathway. In the present study, treatment with curcumin inhibited cell proliferation, induced cell apoptosis and increased the caspase-3 activity of A549 cells. The results also showed that, miR-192-5p relative expression of NCL-H460 cells was relatively lower than that of A549 cells, which was higher, with that of BEAS-2E cells being the highest. miR-192-5p mimics suppressed cell proliferation and increased cell apoptosis of A549 cells. However, anti-miR-192-5p mimics increased cell proliferation and inhibited cell apoptosis of A549 cells. Curcumin treatment effectively increased the relative miR-192-5p expression and suppressed the PI3K/Akt signaling pathway. miR-192-5p mimics enhanced the effect of curcumin on cell viability and apoptosis and suppressed the PI3K/Akt signaling pathway in A549 cells. Anti-miR-192-5p mimics reversed the effect of curcumin on A549 cells and PI3K/Akt expression. Collectively, our findings suggested that curcumin inhibited cell proliferation and induced apoptosis of human non-small cell lung cancer cells through the upregulation of miR-192-5p and suppression of the PI3K/Akt signaling pathway. PMID- 26351876 TI - Targeted inhibition of mitochondrial Hsp90 induces mitochondrial elongation in Hep3B hepatocellular carcinoma cells undergoing apoptosis by increasing the ROS level. AB - Previous studies reported that a Gamitrinib variant containing triphenylphosphonium (G-TPP) binds to mitochondrial Hsp90 and rapidly inhibits its activity to induce apoptosis. We investigated the mechanisms underlying the antitumor activity of G-TPP in Hep3B hepatocellular carcinoma cells. Contrary to our predictions, we observed mitochondrial elongation in the G-TPP-treated Hep3B cells undergoing apoptosis. We found that the G-TPP-induced mitochondrial elongation in Hep3B cells was caused by a decrease in the mitochondrial fission regulating protein Drp1 rather than by changes in the mitochondrial fusion machinery proteins Mfn1 and Opa1. Furthermore, G-TPP induced G2-M phase cell cycle arrest by reducing the interaction between CDK1 and cyclin B1. Additionally, reactive oxygen species (ROS) played a pivotal role in G-TPP induced cell death and mitochondrial elongation in Hep3B cells, and these processes are mediated by the reduced association of CDK1 with cyclin B1 and the suppressed phosphorylation of Drp1 (Ser616). Thus, G-TPP induces cell death and causes Drp1-mediated mitochondrial elongation in Hep3B cells by increasing the ROS level. PMID- 26351879 TI - High Concentrations of Organic Contaminants in Air from Ship Breaking Activities in Chittagong, Bangladesh. AB - The beaches on the coast of Chittagong in Bangladesh are one of the most intense ship breaking areas in the world. The aim of the study was to measure the concentrations of organic contaminants in the air in the city of Chittagong, including the surrounding ship breaking areas using passive air samplers (N = 25). The compounds detected in the highest amounts were the polycyclic aromatic hydrocarbons (PAHs) and short-chain chlorinated paraffins (SCCPs), whereas dichlorodiphenyltrichloroethanes (DDTs), hexachlorobenzene (HCB), and polychlorinated biphenyls (PCBs) were several orders of magnitude lower in comparison. PCBs, PAHs, and HCB were highest at sites near the ship breaking activities, whereas DDTs and SCCPs were higher in the urban areas. Ship breaking activities likely act as atmospheric emission sources of PCBs, PAHs, and HCB, thus adding to the international emphasis on responsible recycling of ships. Concentrations of PAHs, PCBs, DDTs, HCB, and SCCPs in ambient air in Chittagong are high in comparison to those found in similar studies performed in other parts of Asia. Estimated toxic equivalent quotients indicate elevated human health risks caused by inhalation of PAHs at most sites. PMID- 26351878 TI - Structure-Based Design of Human TLR8-Specific Agonists with Augmented Potency and Adjuvanticity. AB - Human Toll-like receptor 8 (hTLR8) is expressed in myeloid dendritic cells, monocytes, and monocyte-derived dendritic cells. Engagement by TLR8 agonists evokes a distinct cytokine profile which favors the development of type 1 helper T cells. Crystal structures of the ectodomain of hTLR8 cocrystallized with two regioisomers of a dual TLR7/8-agonistic N1-substituted imidazoquinolines showed subtle differences in their interactions in the binding site of hTLR8. We hypothesized that the potency of a previously reported best-in-class pure TLR8 agonist, 3-pentylquinoline-2-amine, could be further enhanced by "designing in" functional groups that would mimic key intermolecular interactions that we had observed in the crystal structures. We performed a focused exploration of decorating the quinoline core with alkylamino groups at all possible positions. These studies have led to the identification of a novel TLR8 agonist that was ~ 20-fold more potent than the parent compound and displays prominent adjuvantic activity in a rabbit model of immunization. PMID- 26351881 TI - Ferric-Thiolate Bond Dissociation Studied with Electronic Structure Calculations. AB - The stability and reactivity of iron-sulfur clusters are fundamental properties for the biological function of these prosthetic groups. Here, we investigate the ferric-thiolate bond dissociation of model iron-sulfur tetrahedral complexes with high-level ab initio multiconfigurational electronic structure calculations. We find that the reaction mechanism is homolytic with a spin-crossing from the sextet state in the reactant to quartet state in the product. We also compare several density functionals and semiempirical configuration interaction with the high-level ab initio results to find an accurate but computationally more efficient method to describe the reaction. The functionals M06 and those based on the OPTX exchange functional show the best performance and may reasonably describe the various electron correlation effects involved in ferric-thiolate bond dissociation. PMID- 26351880 TI - Aortic Binding of AZD5248: Mechanistic Insight and Reactivity Assays To Support Lead Optimzation. AB - The oral dipeptidyl peptidase 1 (DPP1) inhibitor AZD5248 showed aortic binding in a rat quantitative whole-body autoradiography (QWBA) study, and its development was terminated prior to human dosing. A mechanistic hypothesis for this finding was established invoking reactivity with aldehydes involved in the cross-linking of elastin, a major component of aortic tissue. This was tested by developing a simple aldehyde chemical reactivity assay and a novel in vitro competitive covalent binding assay. Results obtained with AZD5248, literature compounds, and close analogues of AZD5248 support the mechanistic hypothesis and provide validation for the use of these assays in a two tier screening approach to support lead optimization. The strengths and limitations of these assays are discussed. PMID- 26351882 TI - Applications and Advances in Robotic-Assisted Oncological Surgery: Ready to Dock the 'Bot. PMID- 26351883 TI - Robotic-Assisted Laparoscopic Radical Prostatectomy. AB - BACKGROUND: The use of radical prostatectomy for the treatment of prostate cancer has been increasing during the last decade partially due to the widespread adoption of the robotic-assisted laparoscopic technique. Although no prospective, randomized controlled trials have compared open radical prostatectomy (ORP) with robotic-assisted laparoscopic radical prostatectomy (RALRP), numerous comparative studies have been retrospectively conducted. METHODS: A systematic review of the literature was performed to clarify the role and advancement of RALRP. Studies comparing ORP with RALRP that measured outcomes of cancer control, urinary and sexual function, and complications were included. A nonsystematic review was utilized to describe the advancements in the techniques used for RALRP. RESULTS: RALRP is the procedure of choice when treating localized prostate cancer. This preference is due to the observed improvement in morbidity rates, as evidenced by decreased rates of blood loss and postoperative pain and similar oncological outcomes when compared with ORP. Robotic assistance during surgery is continually being modified and the techniques advanced, as evidenced by improved nerve sparing for preserving potency and reconstruction of the bladder neck to help in the early recovery of urinary continence. CONCLUSIONS: Morbidity rates should continue to improve with the advancement of minimally invasive techniques for radical prostatectomy. The adoption of robotic assistance during surgery will continue as the applications of robotic-assisted surgery expand into other solid organ malignancies. PMID- 26351884 TI - Robotic-Assisted Renal Surgery. AB - BACKGROUND: Minimally invasive surgical techniques have revolutionized the surgical management of kidney cancer. Current evidence suggests that the surgical developments gained by traditional laparoscopy have been advanced by the robotic platform, particularly as it has been applied to techniques for nephron preservation. METHODS: The medical literature from peer-reviewed journals was reviewed to evaluate the feasibility and efficacy of robotic-assisted surgery in the management of renal cell carcinoma. Particular attention was paid to studies comparing robotic-assisted surgery with more traditional surgical techniques. In this review, we have highlighted the evolution of robotic assistance for renal surgery as it pertains to renal oncology. The differing approaches to standard surgeries are discussed as well as current trends to improve perioperative outcomes.In addition, we have reviewed the application of robotic assistance to more complex cases and highlight technological advancements that have pushed the boundaries of surgical care. RESULTS: Robotic-assisted renal surgery is effective for appropriately selected patients. Robotic-assisted radical nephrectomy provides equivalent outcomes to traditional open and laparoscopic approaches, albeit with added financial burden. Robotic-assisted partial nephrectomy - through either transperitoneal or retroperitoneal access - can provide superior outcomes to laparoscopic approaches due to several technical advantages,including improved instrument articulation. CONCLUSIONS: Robotic assistance has transformed the delivery of surgical care to the patient with renal cell carcinoma. For renal surgery, morbidity and patient satisfaction are potentially improved when using robotic platforms compared with open and traditional laparoscopic approaches without compromising oncological control, and this is particularly true for nephron-sparing surgery. PMID- 26351885 TI - Robotic-Assisted Radical Cystectomy. AB - BACKGROUND: The application and use of robotics during radical cystectomy for the treatment of bladder cancer are still being defined. METHODS: A systematic literature search was conducted, with an emphasis on studies published within the previous 5 years. Areas of interest included patient selection, outcomes, cost, and comparisons of robotic-assisted radical cystectomy to open surgery. RESULTS: Although data are lacking in this field, using robotic assistance for radical cystectomy may lead to improvements in estimated blood loss, time to bowel activity, and reduced hospital stay; however, these improvements come at the cost of increased operative time and have a learning curve. CONCLUSIONS: The widespread adoption of robotic-assisted radical cystectomy has not gained acceptance due to lack of evidence and clinical trials showing superiority over open surgery. PMID- 26351886 TI - Robotic-Assisted Surgery in Gynecological Oncology. AB - BACKGROUND: Robotic-assisted surgery is a technological advancement, and its use is rapidly expanding into the field of gynecological oncology. However, a paucity of evidence exists to prove its superiority over standard laparoscopy. Its cost is also high and it lacks haptic feedback. METHODS: A systematic review of the relevant literature was undertaken to understand the use of robotic-assisted surgery in gynecological oncology. RESULTS: Robotic-assisted surgery is being used for select cases of endometrial cancer and has resulted in the increased utilization of minimally invasive surgery for such patients. Use of robotic assisted surgery among patients who are obese has led to decreased complication rates. Robotic-assisted surgery appears to be more expensive than traditional laparoscopy; however, there are potential cost savings to robotic-assisted surgery, including shorter hospital stays and fewer complications, compared with laparotomy. CONCLUSIONS: The gynecological oncology community is rapidly accepting the use of robotic-assisted surgery. Although randomized controlled trials are lacking, the technology appears to be safe and effective, and it has equivalent oncological outcomes in this patient population. PMID- 26351887 TI - Robotic-Assisted Videothoracoscopic Surgery of the Lung. AB - BACKGROUND: Despite initial concerns about the general safety of videothoracoscopic surgery, minimally invasive videothoracoscopic surgical procedures have advantages over traditional open thoracic surgery via thoracotomy. Robotic-assisted minimally invasive surgery has expanded to almost every surgical specialty, including thoracic surgery. Adding a robotic-assisted surgical system to a videothoracoscopic surgical procedure corrects several shortcomings of videothoracoscopic surgical cameras and instruments. METHODS: We performed a literature search on robotic-assisted pulmonary resections and compared the published robotic series data with our experience at the H. Lee Moffitt Cancer Center & Research Institute. All perioperative outcomes, such as intraoperative data, postoperative complications, chest tube duration, hospital length of stay (LOS), and in-hospital mortality rates were noted. RESULTS: Our literature search found 23 series from multiple surgical centers. We divided the literature into 2 groups based on the year published (2005-2010 and 2011-2014). Operative times from earlier studies ranged from 150 to 240 minutes compared with 90 to 242 minutes for later studies. Conversion rates (to open lung resection) from the earlier studies ranged from 0% to 19% compared with 0% to 11% in the later studies. Mortality rates for the earlier studies ranged from 0% to 5% compared with 0% to 2% for the later studies. Since 2010, our group has performed more than 600 robotic-assisted thoracic surgical procedures, including more than 200 robotic-assisted pulmonary lobectomies, which we also divided into 2 groups. Our median skin-to-skin operative time improved from 179 minutes for our early group (n = 104) to 172 minutes for our later group (n = 104). The overall conversion rate was 9.6% and the emergent conversion rate (for bleeding) was 5% for our robotic-assisted lobectomies. The most common postoperative complications in our cohort were prolonged air leak (> 7 days; 16.8%) and atrial fibrillation (12%). Hospital LOS for the early series ranged from 3 to 11 days compared with 2 to 6 days for the later series. Median hospital LOS decreased from 6 to 4 days. Our mortality rate was 1.4%; 3 in-hospital deaths occurred in the early 40 cases. Mediastinal lymph node (LN) dissection and detection of occult mediastinal LN metastases were improved during robotic-assisted lobectomy for non-small-cell lung cancer, as demonstrated by an overall 30% upstaging rate, including a 19% nodal upstaging rate, in our cohort. CONCLUSIONS: Robotic-assisted videothoracoscopic pulmonary lobectomy appears to be as safe as conventional videothoracoscopic surgical lobectomy, which has decreased perioperative complications and a shorter hospital LOS than open lobectomy. Both mediastinal LN dissection and the early detection of occult mediastinal LN metastatic disease were improved by robotic-assisted videothoracoscopic surgical compared with conventional videothoracoscopic surgical or open thoracotomy. PMID- 26351888 TI - Robotic-Assisted Videothoracoscopic Mediastinal Surgery. AB - BACKGROUND: Tumors of the mediastinum as well as normal thymus glands in patients with myasthenia gravis have traditionally been resected using large and morbid incisions. However, robotic-assisted mediastinal resections are gaining popularity because of the many advantages that the robot provides. However, few comprehensive reviews of the literature on robotic-assisted mediastinal resections exist. METHODS: A systemic review of the current medical literature was performed, excluding cases related to esophageal pathology. These studies were evaluated and their findings are reported in this comprehensive review. Approximately 48 papers met the inclusion criteria for review. RESULTS: Robotic assisted surgical systems are increasingly being used in mediastinal resections. Based on the available literature, robotic-assisted thoracoscopic surgery in the mediastinum is feasible and safe. Robotic-assisted mediastinal surgery appears to be superior to open approaches of the mediastinum and is comparable with videothoracoscopic surgery when patient outcomes are considered. CONCLUSIONS: Increased robotic experience and more studies, including randomized controlled trials, are needed to validate the findings of the current literature. PMID- 26351889 TI - Robotic-Assisted Surgery in the Head and Neck. AB - BACKGROUND: Robotic surgery was first used in medicine in the 1980s for laparoscopic surgery. Since then, several developments have been made in the use of robotic surgery for patients with head and neck cancer. METHODS: A review was performed of the literature on robotic surgery in patients with head and neck cancer. The various sites of application are discussed in depth as well as the functional and oncological outcomes associated with the most common application of transoral robotic surgery (TORS). RESULTS: Robotic surgery has been used in all aspects of head and neck surgery. The results from early studies of TORS have shown at least equivalent functional and oncological outcomes. CONCLUSIONS: Robotic surgery has feasible utility in patients with head and neck cancer; moreover, in several circumstances it may provide superior cosmetic, functional, and oncological outcomes than conventional methods. PMID- 26351890 TI - Robotic-Assisted Esophageal Surgery. AB - BACKGROUND: The adoption of minimally invasive approaches to the management of esophageal disease has been slow, except for the laparoscopic management of gastroesophageal reflux disease. However, the advent of new surgical technologies - in particular, robotic-assisted surgical systems - has revolutionized esophageal surgery. METHODS: The literature was systematically reviewed using the keywords "robotic," "esophageal surgery," "esophagectomy," "fundoplication," and "esophageal myotomy." The reference lists from these articles were then also analyzed. RESULTS: Forty-nine studies were included in our comprehensive review of robotic-assisted esophageal surgery, and they consisted of literature reviews, case reports, retrospective and prospective case series, and randomized controlled trials. CONCLUSIONS: Robotic-assisted esophageal surgery is a safe and effective way of treating esophageal disorders, including gastroesophageal reflux disease, achalasia, leiomyomas, and cancer. The use of robotic surgical systems has many benefits for managing disorders of the esophagus, but more studies, including randomized controlled trials, are necessary. PMID- 26351891 TI - Robotic Whipple Procedure for Pancreatic Cancer: The Moffitt Cancer Center Pathway. AB - BACKGROUND: Resection of malignancies in the head and uncinate process of the pancreas (Whipple procedure) using a robotic approach is emerging as a surgical option. Although several case series of the robotic Whipple procedure have been reported, detailed descriptions of operative techniques and a clear pathway for adopting this technology are lacking. METHODS: We present a focused review of the procedure as it applies to pancreatic cancer and describe our clinical pathway for the robotic Whipple procedure used in pancreatic cancer and review the outcomes of our early experience. A systematic review of the literature is provided, focusing on the indications, variations in surgical techniques, complications, and oncological results of the robotic Whipple procedure. RESULTS: A clinical pathway has been defined for preoperative training of surgeons, the requirements for hospital privileges, patient selection, and surgical techniques for the robotic Whipple procedure. The robotic technique for managing malignant lesions of the pancreas head is safe when following well-established guidelines for adopting the technology. Preliminary data demonstrate that perioperative convalescence may exceed end points when compared with the open technique. CONCLUSIONS: The robotic Whipple procedure is a minimally invasive approach for select patients as part of multidisciplinary management of periampullary lesions in tertiary centers where clinicians have developed robotic surgical programs. Prospective trials are needed to define the short- and long-term benefits of the robotic Whipple procedure. PMID- 26351892 TI - Robotics in Neurosurgery: Evolution, Current Challenges, and Compromises. AB - BACKGROUND: Advances in technology have pushed the boundaries of neurosurgery. Surgeons play a major role in the neurosurgical field, but robotic systems challenge the current status quo. Robotic-assisted surgery has revolutionized several surgical fields, yet robotic-assisted neurosurgery is limited by available technology. METHODS: The literature on the current robotic systems in neurosurgery and the challenges and compromises of robotic design are reviewed and discussed. RESULTS: Several robotic systems are currently in use, but the application of these systems is limited in the field of neurosurgery. Most robotic systems are suited to assist in stereotactic procedures. Current research and development teams focus on robotic-assisted microsurgery and minimally invasive surgery. The tasks of miniaturizing the current tools and maximizing control challenge manufacturers and hinder progress. Furthermore, loss of haptic feedback, proprioception, and visualization increase the time it takes for users to master robotic systems. CONCLUSIONS: Robotic-assisted surgery is a promising field in neurosurgery, but improvements and breakthroughs in minimally invasive and endoscopic robotic-assisted surgical systems must occur before robotic assistance becomes commonplace in the neurosurgical field. PMID- 26351893 TI - Association of Lymphomagenesis and the Reactivation of Hepatitis B Virus in Non Hodgkin Lymphoma. AB - BACKGROUND: Hepatitis B virus (HBV) has been associated with the development of non-Hodgkin lymphoma (NHL) and can be reactivated in patients being treated for NHL. METHODS: Articles published between 2000 and 2015 that discussed an association between NHL and HBV, mechanisms of HBV induction of NHL, and HBV reactivation in patients with NHL were reviewed and the results compiled to help health care professionals better understand the risk of developing NHL in HBV seropositive individuals, describe potential etiologies by which HBV infection may lead to lymphomagenesis, and highlight the recent medical literature with respect to the reactivation of HBV in the setting of NHL. RESULTS: An association exists between HBV infection and NHL development. Immunosuppression due to HBV, chronic viral stimulation, and dysregulation of the immune system are possible ways in which lymphoma can develop in patients with HBV infection. All patients being treated with anti-CD20 antibodies or those from or living in HBV-endemic regions should be tested for hepatitis B surface antigen, core antibody, and surface antibody prior to initiating therapy. HBV DNA polymerase chain reaction (PCR) may also be useful in certain cases. Among HBV-seropositive patients or those with detectable HBV DNA, prophylaxis with an antiviral agent should be initiated for 1 year after NHL therapy. HBV DNA PCR monitoring should be undertaken each month during the course of treatment and every 3 months after treatment for a 1-year duration. CONCLUSIONS: Health care professionals should become more comfortable treating these high-risk patients with NHL as they become more informed about potential lymphomagenesis and the reactivation of HBV. PMID- 26351894 TI - Stromal Overgrowth in a Brenner Tumor or Ovarian Fibroma With Minor Sex Cord Elements? AB - Computed tomography obtained as part of a urinary tract assessment in a 68-year old woman incidentally detected a solid adnexal mass. Bilateral salpingo oophorectomy revealed a unilateral, 4-cm, white to tan-yellow colored, focally calcified, left ovarian mass. Microscopically, the tumor was composed of bland fibroblasts, abundant collagen, and areas of calcification with a minor component composed of nests of epithelial cells with nuclear clefts focally evident, some of which contained central lumens with eosinophilic secretions. The major considerations were fibromatous overgrowth in a Brenner tumor or ovarian fibroma with minor sex cord elements. Immunostains for cytokeratin 7 showed diffuse positivity in the epithelial nests, whereas cytokeratin 20 and inhibin were negative, further supporting the diagnosis of a Brenner tumor. PMID- 26351895 TI - Recurrent Systemic Anaplastic Lymphoma Kinase-Negative Anaplastic Large Cell Lymphoma Presenting as a Breast Implant-Associated Lesion. AB - A woman aged 48 years presented with fevers, chills, weight loss, and night sweats. She had significant lymphadenopathy of the left neck as well as the left axilla. Her history was significant for bilateral breast augmentation with textured silicone implants more than 25 years ago. Excisional biopsy of a cervical lymph node revealed large, atypical cells positive for CD4 and CD30 and negative for Epstein-Barr virus-encoded ribonucleic acid, CD2, CD3, CD5, CD7, CD8, CD15, CD20, pan-keratin, S100, anaplastic lymphoma kinase (ALK), and paired box 5. These findings were consistent with Ann Arbor stage IIIB ALK-anaplastic large cell lymphoma (ALCL). The patient was started on 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone. She initially had no signs or symptoms of breast involvement; however, after developing seroma during the clinical course, the patient underwent capsulectomy and removal of the intact, textured silicone implants. Pathological evaluation demonstrated ALK-ALCL in the left breast capsule with cells displaying a significant degree of pleomorphism with binucleated forms and numerous mitoses. Fluorescence in situ hybridization confirmed the tumor was negative for t(2;5). She presented 8 weeks later showing evidence of recurrent systemic disease. PMID- 26351897 TI - IM-412 inhibits the invasion of human breast carcinoma cells by blocking FGFR mediated signaling. AB - Triple-negative breast cancer (TNBC) is an aggressive cancer with a poor prognosis due to its epithelial-to-mesenchymal transition (EMT) phenotype. Cancer patients often experience several detrimental effects of cancer treatment, such as chemoresistance, radioresistance and the maintenance of cancer stem cells due to EMT. Thus, EMT signaling is considered to be a valuable therapeutic target for cancer treatment, and its inhibition is being attempted as a new treatment option for TNBC patients. Previously, we showed that 3-(2-chlorobenzyl)-1,7-dimethyl-1H imidazo[2,1-f]purine-2,4(3H,8H)-dione (IM-412) inhibits transforming growth factor-beta (TGF-beta)-induced differentiation of human lung fibroblasts through both Smad-dependent and -independent pathways. In the present study, we examined the inhibitory effect of IM-412 on EMT pathways and invasiveness in TNBC cells since the TGF-beta signaling pathway is a typical signaling pathway that functions in EMT. IM-412 not only potently suppressed the migration and invasion of MDA-MB-231 cells, but also lowered the expression of mesenchymal markers and EMT-activating transcription factors in these cells. IM-412 inhibited the activation of several signaling proteins, including Smad2/Smad3, p38MAPK, Akt and JNK, and it also attenuated the phosphorylation of FGFR1 and FGFR3. Collectively, our findings suggest that the synthetic compound IM-412 suppressed the EMT process in MDA-MB-231 cells and thereby effectively inhibited the migration and invasion of these cancer cells. Thus, IM-412 could serve as a novel therapeutic agent for malignant cancers. PMID- 26351898 TI - Modular user interface design for integrated surgical workplaces. AB - Severe bottlenecks in usability and human technology interaction (HTI) of existing surgical workplaces and operating room (OR) equipment can occur today: lack of space, cable as trip hazard, communication problems between sterile and non-sterile staff, and operating errors in the handling of the medical devices. In fact, risks that are caused by poor usability can be critical, and studies show that most are preventable. This issue gets even more challenging in the context of open-OR networks regarding consistent and usable integration of user interfaces (UIs) of independently designed systems in one integrated surgical work system. In this work, a concept of generic UI profiles for the modular integration of a UI has been developed and first prototypes have been implemented. The concept is essentially based on the approach of device profiles developed in the context of the Bundesministerium fur Bildung und Forschung project OR.NET (www.ornet.org). We developed generic UI profiles to map the different interfaces of the medical devices on an integrated surgical UI. The integrated UI design shall be automatically verified according to agreed usability criteria, guidelines, and human error taxonomies. PMID- 26351899 TI - Nonlinear analysis of pupillary dynamics. AB - Pupil size reflects autonomic response to different environmental and behavioral stimuli, and its dynamics have been linked to other autonomic correlates such as cardiac and respiratory rhythms. The aim of this study is to assess the nonlinear characteristics of pupil size of 25 normal subjects who participated in a psychophysiological experimental protocol with four experimental conditions, namely "baseline", "anger", "joy", and "sadness". Nonlinear measures, such as sample entropy, correlation dimension, and largest Lyapunov exponent, were computed on reconstructed signals of spontaneous fluctuations of pupil dilation. Nonparametric statistical tests were performed on surrogate data to verify that the nonlinear measures are an intrinsic characteristic of the signals. We then developed and applied a piecewise linear regression model to detrended fluctuation analysis (DFA). Two joinpoints and three scaling intervals were identified: slope alpha0, at slow time scales, represents a persistent nonstationary long-range correlation, whereas alpha1 and alpha2, at middle and fast time scales, respectively, represent long-range power-law correlations, similarly to DFA applied to heart rate variability signals. Of the computed complexity measures, alpha0 showed statistically significant differences among experimental conditions (p<0.001). Our results suggest that (a) pupil size at constant light condition is characterized by nonlinear dynamics, (b) three well defined and distinct long-memory processes exist at different time scales, and (c) autonomic stimulation is partially reflected in nonlinear dynamics. PMID- 26351900 TI - Computational evaluation of amplitude modulation for enhanced magnetic nanoparticle hyperthermia. AB - Magnetic nanoparticles (MNPs) can interact with alternating magnetic fields (AMFs) to deposit localized energy for hyperthermia treatment of cancer. Hyperthermia is useful in the context of multimodality treatments with radiation or chemotherapy to enhance disease control without increased toxicity. The unique attributes of heat deposition and transfer with MNPs have generated considerable attention and have been the focus of extensive investigations to elucidate mechanisms and optimize performance. Three-dimensional (3D) simulations are often conducted with the finite element method (FEM) using the Pennes' bioheat equation. In the current study, the Pennes' equation was modified to include a thermal damage-dependent perfusion profile to improve model predictions with respect to known physiological responses to tissue heating. A normal distribution of MNPs in a model liver tumor was combined with empirical nanoparticle heating data to calculate tumor temperature distributions and resulting survival fraction of cancer cells. In addition, calculated spatiotemporal temperature changes were compared among magnetic field amplitude modulations of a base 150-kHz sinusoidal waveform, specifically, no modulation, sinusoidal, rectangular, and triangular modulation. Complex relationships were observed between nanoparticle heating and cancer tissue damage when amplitude modulation and damage-related perfusion profiles were varied. These results are tantalizing and motivate further exploration of amplitude modulation as a means to enhance efficiency of and overcome technical challenges associated with magnetic nanoparticle hyperthermia (MNH). PMID- 26351901 TI - Brain tumor classification and segmentation using sparse coding and dictionary learning. AB - This paper presents a novel fully automatic framework for multi-class brain tumor classification and segmentation using a sparse coding and dictionary learning method. The proposed framework consists of two steps: classification and segmentation. The classification of the brain tumors is based on brain topology and texture. The segmentation is based on voxel values of the image data. Using K SVD, two types of dictionaries are learned from the training data and their associated ground truth segmentation: feature dictionary and voxel-wise coupled dictionaries. The feature dictionary consists of global image features (topological and texture features). The coupled dictionaries consist of coupled information: gray scale voxel values of the training image data and their associated label voxel values of the ground truth segmentation of the training data. For quantitative evaluation, the proposed framework is evaluated using different metrics. The segmentation results of the brain tumor segmentation (MICCAI-BraTS-2013) database are evaluated using five different metric scores, which are computed using the online evaluation tool provided by the BraTS-2013 challenge organizers. Experimental results demonstrate that the proposed approach achieves an accurate brain tumor classification and segmentation and outperforms the state-of-the-art methods. PMID- 26351902 TI - Barriers to health education in adolescents: health care providers' perspectives compared to high school adolescents. AB - AIM: Although adolescence is marked by profound and dynamic changes, it is virtually neglected by health care providers, by society, and even by most parents, teachers, and health professionals. The aim of this study was to investigate barriers to health education in adolescents from health care providers' views compared to teens. MATERIALS AND METHODS: The study population consisted of 72 health care providers and 402 high school female students in Northern Iran in 2012. They completed a self-administered questionnaire about their views on barriers to adolescents' health education. RESULTS: It is revealed that the major barrier to adolescents' health education from a health care providers' perspective is "Lack of private room for adolescents' health education", while "Lack of adolescents' interest to content of educational programs" is a significantly greater barrier to health education among adolescents. CONCLUSION: The results suggest that for adolescent health education, specific strategies should be used in adolescent health promotion programs. PMID- 26351903 TI - Parenthood linked to new onset overweight or obesity among Chilean adolescents. AB - OBJECTIVE: To determine whether early parenthood is associated with the onset of overweight/obesity during adolescence. METHODS: Weight status changes between ages 16 and 21 years were measured in 270 Chilean youths. Parenthood by age 21 was assessed by interview. RESULTS: Sixty-three youths became overweight/obese between ages 16 and 21 years (23%), and 24% (n=65) of the total sample were parents by age 21. Bearing a child by age 21 was associated with a two-fold risk of becoming newly overweight or obese (OR=2.6, CI: 1.1, 5.9, p<0.05). Earlier internalizing problems were also associated with the development of overweight/obesity in young mothers. CONCLUSION: Weight status changes from normal to overweight or obese were more likely to occur among young parents than non-parents. This has implications for adolescents' future health given their likelihood of having subsequent pregnancies and the known risks of increased weight at each pregnancy. PMID- 26351904 TI - Physical self-esteem and personality traits in Swedish physically inactive female high school students: an intervention study. AB - BACKGROUND: Physical activity provides fundamental health benefits and plays a positive role in physical well-being. The aim of this present study was to investigate whether a 6-month physical activity program could influence physical self-esteem and frequency of physical activity in physically inactive female high school students in short- and long-term periods and whether personality traits were related to physical activity behaviour and compliance with the program. METHODS: The study was a cluster-randomised controlled intervention study including 104 physically inactive female high school students aged 16-19 years, 60 females in an intervention group and 44 females in a control group. The intervention group exercised at sport centres at least once per week during a 6 month period. Questionnaires were used for evaluation. RESULTS: At a 6-month follow up, the intervention group improved physical self-perception in all subdomains and significantly improved physical condition, physical self-worth and self-related health compared to the control group. At 1-year follow up, 25 females out of 53 females were still physically active, and all ratings remained almost the same as at the 6-month follow up. There were no particular personality traits that were dominant in the groups. CONCLUSION: A 6-month physical activity program can positively influence physical self-esteem and the frequency of physical activity, both from a short- and long-term perspective. PMID- 26351905 TI - Health concerns of adolescents in Tehran, Iran. AB - BACKGROUND: Adolescent health concerns are an important source of information that should be considered when planning school and community health promotion policies, programs and services. Adolescence is a critical period of human development and the health concerns of adolescents can point to important issues that may be eclipsed by epidemiologic and other clinical sources of information. This study aimed to assess the health concerns of adolescents living in Tehran, Iran and to examine associations between selected demographics and the health concerns reported by participants. METHODS: This study was a population-based cross-sectional survey in 2011. Data were collected from a stratified random cluster sample of 915 adolescents, aged 14-18 years, living in Tehran, using the Persian version of the Adolescent Health Concern Inventory (AHCI-P). The data were analyzed using the chi2, Mann-Whitney and Kruskal-Wallis tests and logistic regression analysis. RESULTS: The mean numbers of health concerns in girls and boys were 48 (+/-27.6) and 44.5 (+/-27.4) respectively. The highest ranking health concern subscale for both girls and boys was The Future, and "being successful" was endorsed as the most prominent concern in the subscale. Female (OR: 1.42, CI 95%: 1.08-1.87), mother's educational level (OR: 2.23, CI 95%: 1.07 4.65) and living in northern (OR: 1.76, CI 95%: 1.13-2.74) and western (OR: 2.02, CI 95%: 1.30-3.16) regions of Tehran were significant predictors of a higher level of health concerns. CONCLUSION: Findings can be used to inform school and public health promotion policies, programs and supportive services designed to improve the overall health and well-being of adolescents. PMID- 26351906 TI - Diet quality and physical activity in relation to childhood obesity. AB - OBJECTIVE: Healthy lifestyles such as being physically active and eating a healthy diet help reduce the childhood obesity risk. However, population-level studies on the relationship between lifestyles and childhood obesity typically focus on either physical activity or diet but seldom both. This study examined physical activity and diet quality in relation to obesity in a nationally representative sample of U.S. children and adolescents. METHODS: The study sample of 2818 children 6-17 years old came from the National Health and Nutrition Examination Survey 2003-2006 waves. A healthy eating index (HEI)-2010 was constructed based on two nonconsecutive 24-h dietary recalls. Participants at or above the 60th percentile of the HEI-2010 score were classified as consuming a healthy diet. Participants engaging in at least 60 min of moderate-vigorous physical activity daily measured by accelerometer were classified as being physically active. Adjusted average marginal effect of diet quality and physical activity on obesity was calculated based on estimates from logistic regressions. RESULTS: Compared with those consuming a healthy diet who are physically active, the estimated probabilities for overweight and obesity were 19.03 (95% confidence interval: 11.31, 26.74) and 15.84 (10.48, 21.21) percentage points higher among children consuming an unhealthy diet and who are physically inactive, 16.53 (7.58, 25.48) and 13.48 (5.68, 21.29) percentage points higher among children consuming a healthy diet but who are physically inactive and 3.22 (-3.43, 9.88) and 3.10 (-3.08, 9.29) percentage points higher among children consuming an unhealthy diet but physically active, respectively. CONCLUSION: Healthy habit formation at an early age is essential in obesity prevention. PMID- 26351907 TI - The double mutation L109M and R448M of HIV-1 reverse transcriptase decreases fidelity of DNA synthesis by promoting mismatch elongation. AB - Changes of Leu109 and Arg448 of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) have as yet not been associated with altered fitness. However, in a recent study, we described that the simultaneous substitution of L109 and R448 by methionine leads to an error-producing polymerase phenotype that is not observed for the isolated substitutions. The double mutant increased the error rate of DNA-dependent DNA synthesis 3.1-fold as compared to the wildtype enzyme and showed a mutational spectrum with a fraction of 28% frameshift mutations and 48% transitions. We show here that weaker binding of DNA:DNA primer templates as indicated by an increased dissociation rate constant (koff) could account for the higher frameshift error rate. Furthermore, we were able to explain the prevalence of transition mutations with the finding that HIV-1 RT variant L109M/R448M preferred misincorporation of C opposite A and elongation of C:A mismatches. PMID- 26351908 TI - Up-regulation of miR-125b reverses epithelial-mesenchymal transition in paclitaxel-resistant lung cancer cells. AB - Recent studies have demonstrated that acquisition of epithelial-mesenchymal transition (EMT) is associated with drug resistance in lung cancer cells. However, the underlying mechanisms are not fully elucidated. Emerging evidence suggests that microRNAs play a crucial role in controlling EMT. The aim of this study was to explore the potential role of miR-125b in governing EMT in paclitaxel-resistant (PR) lung cancer cells. To achieve this goal, we explored the role of miR-125b in regulation of EMT in stable PR lung cancer cells, namely A549-PR and H460-PR. We found that miR-125b was significantly downregulated in A549-PR and H460-PR cells. Notably, ectopic expression of miR-125b led to the reversal of EMT phenotype. Moreover, we found that miR-125b governed PR-induced EMT partly due to down-regulation of its target Sema4C. More importantly, overexpression of miR-125b or depletion of Sema4C sensitized PR cells to paclitaxel. Furthermore, stable overexpression miR-125b in A549-PR cells inhibited tumor xenograft growth in immunodeficient mice. Our study implied that up-regulation of miR-125b could be a novel approach to reverse chemotherapy resistance in lung cancers. PMID- 26351909 TI - Ancestral protein reconstruction: techniques and applications. AB - Ancestral sequence reconstruction (ASR) is the calculation of ancient protein sequences on the basis of extant ones. It is most powerful in combination with the experimental characterization of the corresponding proteins. Such analyses allow for the study of problems that are otherwise intractable. For example, ASR has been used to characterize ancestral enzymes dating back to the Paleoarchean era and to deduce properties of the corresponding habitats. In addition, the historical approach underlying ASR enables the identification of amino acid residues key to protein function, which is often not possible by only comparing extant proteins. Along these lines, residues responsible for the spectroscopic properties of protein pigments were identified as well as residues determining the binding specificity of steroid receptors. Further applications are studies related to the longevity of mutations, the contribution of gene duplications to enzyme functionalization, and the evolution of protein complexes. For these applications of ASR, we discuss recent examples; moreover, we introduce the basic principles of the underlying algorithms and present state-of-the-art protocols. PMID- 26351910 TI - The macromolecular crowding effect--from in vitro into the cell. AB - The influence of the cellular milieu, a complex and crowded solvent, is often neglected when biomolecular structure and function are studied in vitro. To mimic the cellular environment, crowding effects are commonly induced in vitro using artificial crowding agents like Ficoll or dextran. However, it is unclear if such effects are also observed in cellulo. Diverging results on protein stability in living cells point out the need for new quantitative methods to investigate the contributions of excluded volume and nonspecific interactions to the cellular crowding effect. We show how new crowding sensitive probes may be utilized to directly investigate crowding effects in living cells. Moreover, we discuss processes where crowding effects could play a crucial role in molecular cell biology. PMID- 26351911 TI - The role of Bni5 in the regulation of septin higher-order structure formation. AB - Septins are a family of conserved cytoskeletal proteins playing an essential role in cytokinesis and in many other cellular processes in fungi and animals. In budding yeast Saccharomyces cerevisiae, septins form filaments and higher-order structures at the mother-bud neck depending on the particular stage of the cell cycle. Septin structures at the division plane serve as a scaffold to recruit the proteins required for particular cellular processes. The formation and localization of septin structures at particular stages of the cell cycle also determine functionality of these proteins. Many different proteins participate in regulating septin assembly. Despite recent developments, we are only beginning to understand how specific protein-protein interactions lead to changes in the polymerization of septin filaments or assembly of higher-order structures. Here, using fluorescence and electron microscopy, we found that Bni5 crosslinks septin filaments into networks by bridging pairs or multiple filaments, forming structures that resemble railways. Furthermore, Bni5 appears to be a substrate of the Elm1 protein kinase in vitro. Moreover, Elm1 induces in the presence of Bni5 disassembly of long septin filaments, suggesting that these proteins may participate in the hourglass to double ring transition. This work gives new insight into the regulatory role of Bni5 in the structural changes of septins. PMID- 26351912 TI - Inactivation of human kininogen-derived antimicrobial peptides by secreted aspartic proteases produced by the pathogenic yeast Candida albicans. AB - Ten secreted aspartic proteases (Saps) of Candida albicans cleave numerous peptides and proteins in the host organism and deregulate its homeostasis. Human kininogens contain two internal antimicrobial peptide sequences, designated NAT26 and HKH20. In our current study, we characterized a Sap-catalyzed cleavage of kininogen-derived antimicrobial peptides that results in the loss of the anticandidal activity of these peptides. The NAT26 peptide was effectively inactivated by all Saps, except Sap10, whereas HKH20 was completely degraded only by Sap9. Proteolytic deactivation of the antifungal potential of human kininogens can help the pathogens to modulate or evade the innate immunity of the host. PMID- 26351913 TI - The importin alpha/beta-specific inhibitor Ivermectin affects HIF-dependent hypoxia response pathways. AB - Hypoxia-inducible transcription factors (HIFs) regulate hundreds of genes involved in cellular adaptation to reduced oxygen availability. HIFs consist of an O2-labile alpha-subunit (primarily HIF-1alpha and HIF-2alpha) and a constitutive HIF-1beta subunit. In normoxia the HIF-alpha subunit is hydroxylated by members of a family of prolyl-4-hydroxylase domain (PHD) proteins, PHD1-3, resulting in recognition by von Hippel-Lindau protein, ubiquitination and proteasomal degradation. In contrast, reduced oxygen availability inhibits PHD activity resulting in HIF-1alpha stabilisation and nuclear accumulation. Nuclear import of HIF-1alpha mainly depends on classical nuclear localisation signals (NLS) and involves importin alpha/beta heterodimers. Recently, a specific inhibitor of nuclear import has been identified that inhibits importin alpha/beta dependent import with no effects on a range of other nuclear transport pathways involving members of the importin protein family. In this study we evaluated the physiological activity of this importin alpha/beta-inhibitor (Ivermectin) in the hypoxia response pathway. Treatment with Ivermectin decreases binding activity of HIF-1alpha to the importin alpha/beta-heterodimer. Moreover, HIF-1alpha nuclear localisation, nuclear HIF-1alpha protein levels, HIF-target gene expression, as well as HIF-transcriptional activity are reduced upon Ivermectin treatment. For the first time, we demonstrate the effect of specific importin alpha/beta inhibition on the hypoxic response on the molecular level. PMID- 26351914 TI - The role of the Lowe syndrome protein OCRL in the endocytic pathway. AB - Mutations of the inositol-5-phosphatase OCRL cause Lowe syndrome and Dent-II disease. Both are rare genetic disorders characterized by renal defects. Lowe syndrome is furthermore characterized by defects of the eye (congenital cataracts) and nervous system (mental disabilities, hypotonia). OCRL has been localised to various endocytic compartments suggesting impairments in the endocytic pathway as possible disease mechanism. Recent evidence strongly supports this view and shows essential roles of OCRL at clathrin coated pits, transport of cargo from endosomes to the trans-Golgi network as well as recycling of receptors from endosomes to the plasma membrane. In particular in vitro and in vivo evidence demonstrates an important role of OCRL in recycling of megalin, a multi-ligand receptor crucial for reabsorption of nutrients in the proximal tubulus, a process severely impaired in Lowe syndrome patients. Thus defects in the endocytic pathway are likely to significantly contribute to the kidney phenotype in Lowe syndrome and Dent-II disease. PMID- 26351915 TI - How to build the fastest receptor on earth. AB - In 2014, a slew of structures of glutamate receptors were published, based on crystallography and electron microscopy. Here we review these insights, integrate them with existing knowledge about receptor function and try to understand how the structures relate to the key property of the AMPA receptor--its speed. PMID- 26351916 TI - Systematic analysis of the contribution of c-myc mRNA constituents upon cap and IRES mediated translation. AB - Fine tuning of c-MYC expression is critical for its action and is achieved by several regulatory mechanisms. The contribution of c-myc mRNA regulatory sequences on its translational control has been investigated individually. However, putative interactions have not been addressed so far. The effect of these interactions upon the translatability of monocistronic and bicistronic chimaeric mRNAs, carrying combinations of the c-myc mRNA 5'-untranlated region (UTR), 3'-UTR, and coding region instability element (CRD) was investigated on this study. The presence of the 5'-UTR induced an increase in translatability of 50%. The presence of the CRD element, when in frame, reduced translatability by approximately 50%, regardless of the expression levels of the wild type CRD- binding protein (CRD-BP/IMP1). Conversely, overexpression of a mutated CRD BP/IMP1 (Y396F) further impeded translation of the chimaeric mRNAs carrying its cognate sequences. The presence of the c-myc 3'-UTR increased translatability by approximately 300% affecting both cap and c-myc internal ribosome entry site (IRES) mediated translation. In addition, 3'-UTR rescued the cap mediated translation in the presence of the polyadenylation inhibitor cordycepin. Furthermore, the 3'-UTR rescued cap mediated translation under metabolic stress conditions and this was enhanced in the absence of a long poly (A) tail. PMID- 26351917 TI - IsoQC (QPCTL) knock-out mice suggest differential substrate conversion by glutaminyl cyclase isoenzymes. AB - Secretory peptides and proteins are frequently modified by pyroglutamic acid (pE, pGlu) at their N-terminus. This modification is catalyzed by the glutaminyl cyclases QC and isoQC. Here, we decipher the roles of the isoenzymes by characterization of IsoQC-/- mice. These mice show a significant reduction of glutaminyl cyclase activity in brain and peripheral tissue, suggesting ubiquitous expression of the isoQC enzyme. An assay of substrate conversion in vivo reveals impaired generation of the pGlu-modified C-C chemokine ligand 2 (CCL2, MCP-1) in isoQC-/- mice. The pGlu-formation was also impaired in primary neurons, which express significant levels of QC. Interestingly, however, the formation of the neuropeptide hormone thyrotropin-releasing hormone (TRH), assessed by immunohistochemistry and hormonal analysis of hypothalamic-pituitary-thyroid axis, was not affected in isoQC-/-, which contrasts to QC-/-. Thus, the results reveal differential functions of isoQC and QC in the formation of the pGlu peptides CCL2 and TRH. Substrates requiring extensive prohormone processing in secretory granules, such as TRH, are primarily converted by QC. In contrast, protein substrates such as CCL2 appear to be primarily converted by isoQC. The results provide a new example, how subtle differences in subcellular localization of enzymes and substrate precursor maturation might influence pGlu-product formation. PMID- 26351918 TI - Melanoma differentiation-associated gene 5 is involved in the induction of stress granules and autophagy by protonophore CCCP. AB - The eukaryotic cell has evolved a variety of stress responses against external stimuli, such as innate immunity, the formation of stress granules (SGs), and autophagy. We previously demonstrated that the innate immune adaptor IFN-beta promoter stimulator 1 (IPS-1) plays an essential role in the formation of dsRNA induced SGs, indicating a connection between SG formation and innate immunity. In this study, it was further demonstrated that melanoma differentiation-associated gene 5 (MDA5), an innate immune sensor, is involved in SG formation induced by carbonyl cyanide m-chlorophenylhydrazone (CCCP), a mitochondrial protonophore. MDA5 knockdown had no significant impact on the phosphorylation of eukaryotic translation initiation factor 2alpha (eIF2alpha) triggered by CCCP, and MDA5 itself was not recruited to SGs, suggesting that the regulation of MDA5 in the SG response occurs downstream of eIF2alpha. Furthermore, the depletion of MDA5 or G3BP1 led to reduced autophagy in CCCP-stimulated cells, implying that the regulatory effect of MDA5 with respect to autophagy depends on its role in SG formation. This study uncovered an unexpected role of the innate immune protein MDA5 in SG formation and autophagy triggered by the protonophore CCCP, further supporting a correlation between different stress responses. PMID- 26351919 TI - Mapping the non-standardized biases of ribosome profiling. AB - Ribosome profiling is a new emerging technology that uses massively parallel amplification of ribosome-protected fragments and next-generation sequencing to monitor translation in vivo with codon resolution. Studies using this approach provide insightful views on the regulation of translation on a global cell-wide level. In this review, we compare different experimental set-ups and current protocols for sequencing data analysis. Specifically, we review the pitfalls at some experimental steps and highlight the importance of standardized protocol for sample preparation and data processing pipeline, at least for mapping and normalization. PMID- 26351920 TI - What can lipidomics tell us about the pathogenesis of Alzheimer disease? AB - Lipids serve many distinct functions in cellular homeostasis such as membrane organization, as a platform for membrane function and protein/protein or protein/lipid interaction, energy storage, as well as secondary messengers in signal transduction. Perturbations in lipid homeostasis may result in abnormal cellular function. Alzheimer's disease (AD) is a neurodegenerative disorder in which the brain represents the primary site of pathology. While there is a plethora of previous work pertaining to AD pathogenesis, the precise mechanism of the disease is still not well-understood. Recent waves of technological advances in the realm of lipidomics have enabled scientists to look at AD pathogenesis from a previously unexplored perspective, and studies have revealed extensive lipid aberrations are implicated in the disease pathology. Herein, we review the critical lipids alternations, which affect amyloid plaque and neurofibrillary tangles formation and accumulation, as well as lipid aberrations related to neuronal and synaptic dysfunction in cells and animal models. We also summarize lipid abnormalities observed in the human cerebrospinal fluid (CSF), as well as other circulating fluids including plasma and serum in association with AD, which could serve as candidate biomarkers to diagnose and monitor the disease. PMID- 26351921 TI - Phenobarbital inhibits calpain activity and expression in mouse hepatoma cells. AB - The antiepileptic drug phenobarbital (PB) exerts hepatic effects related to cell proliferation and tumorigenesis which are closely linked to the Wnt/beta-catenin signaling pathway. This pathway is, amongst others, regulated by calpain proteases. We now identified PB as an inhibitor of Wnt/beta-catenin signaling in mouse hepatoma cells. Further analyses revealed that PB inhibits calpain activity, an effect which is at least in parts mediated by a transcriptional regulation of calpain mRNA levels and which is furthermore independent of the constitutive androstane receptor, the known mediator of most effects of PB in liver cells. PMID- 26351922 TI - The role of timely measurement of galectin-3, NT-proBNP, cystatin C and hsTnT in predicting prognosis and heart function after heart transplantation. AB - BACKGROUND: Changes of biomarkers measured soon after heart transplantation (HTx) can reflect different processes: cardiomyocyte necrosis (troponins, high sensitivity cardiac TnT and TnI), heart function (natriuretic peptides, BNP and NT-proBNP), fibrosis (galectin-3 and ST2), and global cardiorenal risk (cystatin C). We assessed the prognostic role of hsTnT, NT-proBNP, galectin-3 and cystatin C during the early post-transplant period. METHODS: A total of 121 consecutive post-HTx patients were assessed. The main outcomes were survival, left ventricular ejection fraction (LVEF) and rejection periods. Survival was assessed after intermediate (12 months) and long periods (total follow-up during study, median of survival 763 days, IR 527-1038 days). LVEF was assessed 12 months after HTx. Rejection was evaluated during follow-up. We report biomarker concentrations measured 10 days and 12 months after HTx. RESULTS: Ten days after HTx, cystatin C and hsTnT predicted death both under univariable and multivariable analysis. These two biomarkers along with galectin-3 were increased in patients with decreased LVEF measured 1 year after HTx. NT-proBNP did not show early prognostic power. None of the measured biomarkers predicted rejection, but hsTnT and NT proBNP were increased significantly 12 months after HTx in patients with at least one rejection. CONCLUSIONS: Cystatin C and hsTnT measured 10 days after HTx can provide prognostic information on survival and galectin-3 measured at the same time may display a relationship to heart function assessed 1 year after HTx. Further study should be carried out in a large cohort of patients. PMID- 26351923 TI - Rapid detection of non-deletional mutations causing alpha-thalassemia by multicolor melting curve analysis. AB - BACKGROUND: alpha-Thalassemia, caused by mutations in the alpha-globin genes, is one of the most common monogenic inherited disorders in the world. However, non deletional alpha-thalassemia mutations remain undetected in routine clinical testing due to the lack of a suitable method. In this study, a closed- and single tube assay for the detection of six common non-deletional alpha-thalassemia mutations in the HBA2 gene was developed based on multicolor melting curve analysis. METHODS: The assay consisted of one pair of primers specific for the HBA2 gene and four dual-labeled, self-quenched probes targeting six non deletional alpha-thalassemia mutations. The sensitivity, reproducibility, and accuracy of the method were validated via 700 genomic DNA samples. RESULTS: The assay had a reproducibility of 100%, could detect gDNA of different genotype as low as 1 ng per reaction, and had an overall accuracy of 100% when compared with RDB analysis and Sanger sequencing. CONCLUSIONS: The developed assay is rapid, robust, and cost-effective while maintaining high sensitivity, specificity, and throughput. PMID- 26351924 TI - Relationship between matrix metalloproteinase-9 and oxidative stress in drug-free male schizophrenia: a case control study. AB - BACKGROUND: Deregulation of synaptic plasticity and oxidative stress are reported to play a crucial role in the pathogenesis of schizophrenia. Matrix metalloproteinase-9 (MMP-9) is an extracellular protease involved in regulation of synaptic plasticity. Malondialdehyde (MDA) is a marker of lipid peroxidation which is elevated in schizophrenia. Earlier studies have reported polymorphism of MMP-9 and its association with schizophrenia. The present study was designed to assess the serum levels of MMP-9, MDA and total antioxidant status (TAS) and their association in schizophrenia. METHODS: A total of 40 cases and 40 controls were included in the study. Serum MMP-9, MDA and TAS were estimated in all the subjects. Disease severity was assessed using Positive and Negative Syndrome Scale (PANSS). RESULTS: MMP-9 and MDA were significantly increased and TAS were significantly reduced in schizophrenia cases compared to controls. MMP-9 was positively correlated with MDA (r=0.353, p=0.025) and negatively correlated with TAS (r=-0.461, p=0.003). TAS was significantly correlated with total (r=0.322, p=0.043) and negative symptom scores (r=0.336, p=0.034). Higher MMP-9 levels were associated with previous exposure to antipsychotics (p=0.032). CONCLUSIONS: MMP-9 and oxidative stress were increased and correlate well with each other in schizophrenia cases. Though total oxidant status showed positive association with disease severity, MMP-9 and MDA were not associated with the severity of the disease. PMID- 26351925 TI - Neutrophil CD64 combined with PCT, CRP and WBC improves the sensitivity for the early diagnosis of neonatal sepsis. AB - BACKGROUND: The aim of this study was to determine whether neutrophil CD64 (nCD64) combined with procalcitonin (PCT), C-reactive protein (CRP) and white blood cell count (WBC) can increase the sensitivity and accuracy of neonatal sepsis diagnosis. METHODS: The serum levels of nCD64, CRP, PCT and WBC were detected in 60 patients with neonatal sepsis and 60 patients with non-sepsis. Sensitivity, specificity, positive and negative predictive values, receiver operating characteristic (ROC) area under the curve (AUC), and logistic regression analysis were performed to evaluate the diagnostic value of these markers on neonatal sepsis. RESULTS: Serum levels of nCD64, PCT, CRP and WBC were higher in the sepsis group than non-sepsis group (p<0.001). The sensitivities of nCD64, PCT, CRP and WBC at the recommended cut-off level for all infants were 79.5%, 68.2%, 38.6% and 52.3%, respectively. The best combination was nCD64 and PCT, which obtained sensitivity of 90.9%, largest AUC of 0.922, and a negative predictive value of 89.2%. However by using an optimal cut-off value, the sensitivities of all four biomarkers for the diagnosis of neonatal sepsis were increased to 95.5%. Except for WBC, the birth weight and gestational age had no effects on the diagnostic value of these serum biomarkers. CONCLUSIONS: nCD64 and PCT are better diagnostic biomarkers for early diagnosis of neonatal sepsis as compared to CRP. With the help of optimal cut-off value based on ROC curve and logistic regression analysis, the combination of these biomarkers could improve the sensitivity for the diagnosis of suspected late-onset neonatal sepsis based on common serum biomarkers. PMID- 26351926 TI - Patient pools and the use of "patient means" are valuable tools in quality control illustrated by a bone-specific alkaline phosphatase assay. AB - BACKGROUND: Quality control (QC) is an essential part of clinical biochemistry to ensure that laboratory test results are reliable and correct. Those tests without a defined reference method constitute a special challenge, as is the case with bone-specific alkaline phosphatase (BAP). METHODS AND RESULTS: The present study reports an example where a shift in a BAP assay was detected by use of a patient pool and supported by a retrospective calculation of "patient mean", while the external QC and specific assay control material were unaffected by the shift. CONCLUSIONS: Patient pools and the use of patient means remain a useful and inexpensive procedure for internal QC. PMID- 26351927 TI - Pharmacokinetics of a novel dosing regimen of oral melatonin in critically ill patients. AB - BACKGROUND: Loss of circadian rhythms and reduced concentrations of endogenous melatonin are common in critically ill patients. After exogenous administration, supra-physiological concentrations in serum are only ephemeral, which may explain the absence of significant therapeutic effect on sleep. The aim of this study is to describe the pharmacokinetics of enteral melatonin in critically ill patients administered in a novel regimen aiming to simulate endogenous release. METHODS: Thirteen patients in the recovery phase of critical illness were randomised to receive enteral melatonin or placebo. In the melatonin group, a total of 6 mg was administered as solution through their feeding tube, commencing with a 3 mg loading dose at 9 pm and six subsequent 0.5 mg doses hourly. The placebo was administered using a similar regimen. Serial blood samples were taken and measured using a validated chromatographic method. The concentration-time data for serum melatonin concentrations were described using non-linear mixed-effects modelling. RESULTS: The observed concentrations in the melatonin patients were significantly higher than that observed in the placebo patients. The concentrations in the patients administered melatonin were also higher than endogenous melatonin concentrations previously reported in non-critically ill patients. The patients administered melatonin had a mean clearance, volume of distribution and absorption rate constant of melatonin was 55.2 L/h, 767 L and 0.76 h-1, respectively. CONCLUSIONS: Exogenous administration of melatonin with a loading dose of 3 mg followed by an hourly dose of 0.5 mg demonstrates good oral bioavailability and results in supra-physiological and sustained concentrations of serum melatonin during 12 h overnight. PMID- 26351928 TI - Effects of biobanking conditions on six antibiotic substances in human serum assessed by a novel evaluation protocol. AB - BACKGROUND: Although therapeutic drug monitoring (TDM) for antibiotics in critically ill patients is recommended by expert panels, no commercial tests are available for most antibiotics. Therefore, we previously developed a multi analyte method for the quantification of piperacillin, tazobactam, cefepime, meropenem, ciprofloxacin and linezolid in serum. However, limited stability data were available, and the relevant studies did not address the coefficients of variation of the methods applied, which may be important for verifying the storage dependency of the observed effects. Here we aimed to evaluate the storage effects of antibiotics by applying a novel evaluation protocol. METHODS: Serum based test samples were aliquoted and stored at room temperature, 4 degrees C, 20 degrees C or -80 degrees C for up to 180 days. Using an innovative evaluation protocol (considering the coefficient of variation, p-value, and criterion of monotony of observed changes), we assessed whether relevant changes (defined as >=15% in comparison with baseline) were storage dependent (defined as substantial changes). RESULTS: Storage at -80 degrees C for up to 180 days did not lead to substantial changes for any analyte. In contrast, storage at -20 degrees C induced substantial decreases after >=7 days for piperacillin, tazobactam, cefepime and meropenem; after 90 days at -20 degrees C, only <=23% of the initial concentrations were found for these parameters. No substantial changes were observed for linezolid and ciprofloxacin at any storage condition. All of the observed substantial changes were monotonic decreases. CONCLUSIONS: We recommend a storage temperature of -80 degrees C for beta-lactam antibiotics. The applied evaluation protocol yielded conclusive results and may be generally useful for stability studies. PMID- 26351929 TI - An epidemiology-based model as a tool to monitor the outbreak of inappropriateness in tumor marker requests: a national scale study. AB - BACKGROUND: Evaluation of appropriateness of laboratory tests on the basis of individual requests remains a serious problem as the clinical question is usually not reported with the test order. This study explored the comparison of the rate of tumor marker orders with cancer prevalence as a putative indicator of inappropriateness. METHODS: Tumor marker orders (2011 and 2012) were obtained from the Ministry of Health and cancer prevalence from the Italian Association of Cancer Registries. The rate of tumor marker orders was matched with demographic data and tumor prevalence and examined by using the confidence interval approach. Region-to-region and year-to-year variations were also examined. Focus was placed on CEA, CA125, CA19.9 and CA15.3. RESULTS: Tumor markers ordered in Italy were 13,207,289 in 2012 (221.3/1000 individuals). Given an estimated prevalence of 2,243,953 cancer cases, 7.04 tumor markers appear to be requested for each prevalent case of epithelial cancer per year. The rate of requests of CEA, CA125, CA19.9 and CA15.3 (in aggregate 5,834,167 requests in 2012, 44.2% of total) from the first and the last ranked region (96 and 244/1000 individuals) are significantly different (p<0.01). Region-to-region differences do not correspond to any known variation of prevalence in the different regions. CONCLUSIONS: The developed approach provides a proxy indicator of inappropriateness showing that tumor markers are overused in Italy and their ordering pattern is not related to tumor prevalence. The model is suitable to be validated in other laboratory tests used in diseases whose prevalence is known. PMID- 26351930 TI - Comparison of functional fibrinogen (FF/CFF) and FIBTEM in surgical patients - a retrospective study. AB - BACKGROUND: Fibrinogen-based clot firmness is reported as the maximum amplitude (MA) when using the citrated functional fibrinogen (CFF) assay in thrombelastography (TEG), and as the maximum clot firmness (MCF) together with several clot amplitude parameters when using the FIBTEM assay in thromboelastometry (ROTEM). Concern is currently being raised that these two tests have different platelet inhibiting performance and consequently provide different values. This is relevant for the clinical setting of fibrinogen replacement. We aim herein to compare the parameters of these two fibrinogen based clot quality tests and their correlation with the plasma fibrinogen level as determined by the Clauss method. METHODS: In total 261 whole blood samples taken from 163 clinical routine surgical patients were analyzed with TEG 5000 and ROTEM tests, and correlation with Clauss fibrinogen level was assessed. RESULTS: Using TEG, the overall fibrin-based clot firmness measured in the CFF assay was significantly higher than the MCF measured by FIBTEM assay. Both assays showed significantly positive correlations with the fibrinogen levels measured using the Clauss method. However, individual values of Clauss fibrinogen concentration corresponded with different values for the two viscoelastometric tests; e.g. within the range of 1.9-2.1 g/L Clauss fibrinogen the median of CFF MA was 16.3 mm whereas FIBTEM MCF was 12.0 mm. CONCLUSIONS: We showed herein by measurements of citrated whole blood samples from surgical patients that CFF MA values were different from FIBTEM MCF values measured in the same sample. Awareness that these whole blood assays provide different clot amplitude results is mandatory, particularly if they are being considered as tools for guiding fibrinogen supplementation. Thromboembolic side effects caused by a potentially too high fibrinogen substitution must also kept in mind in this context. PMID- 26351931 TI - Concomitant appearance of two false positive peaks with a true monoclonal one in a patient with plasma cell myeloma. PMID- 26351932 TI - Diagnostic and clinical significance of Crohn's disease-specific pancreatic anti GP2 and anti-CUZD1 antibodies. AB - BACKGROUND: Pancreatic autoantibodies (PAB) targeting GP2 and CUZD1 are Crohn's disease (CrD)-markers. The clinical significance of anti-GP2 antibodies has been assessed, but that of anti-CUZD1 remains elusive. The aim of the study was to assess the clinical utility of anti-CUZD1/anti-GP2 by novel cell-based indirect immunofluorescence (IIF) assays in CrD. METHODS: A total of 212 CrD and 249 UC patients followed up at a London IBD centre were investigated to simultaneously detect PABs, anti-GP2 and anti-CUZD1 by IIF using primate pancreatic tissue, and HEK293 over-expressing CUZD1 or GP2. RESULTS: Overall, 88 (41.5%) CrDs compared to 26 (10.4%) UCs (p<0.001) tested positive for IgA and/or IgG anti-GP2 and/or anti-CUZD1 antibodies, while ASCA were found in 67.5% CrDs versus 19.2% UCs (p<0.0001); ASCA and/or PAB (anti-GP2 or anti-CUZD1) were detected in 76% CrD versus 34% UC patients. IgG anti-GP2 antibodies were less prevalent in L2 phenotype (p=0.002) and more prevalent in patients with stricturing disease (p=0.0418), even when a higher cut-off (>=1000 RU) was used (p=0.0396). Also, anti-GP2 IgG positive CrD patients had younger age of disease onset. IgA and/or IgG ASCA and anti-GP2 IgG antibody positive CrDs had younger onset of disease (p<0.0001), were more likely to have both ileal and colonic disease (p<0.0001) and had more stricturing (p<0.0001) than seronegative patients. Clinical correlates were not found for anti-CUZD1 positivity. CONCLUSIONS: PAB testing increases ASCA's serological sensitivity for CrD. Anti-GP2 detection, in isolation or in combination with ASCA, stratify CrD patients who phenotypically are characterised by a much younger onset of disease, extensive and stricturing behaviour. PMID- 26351933 TI - Application of fatty acid and lipid measurements in neuropsychiatry. AB - The importance of lipids in the understanding of disease states is constantly increasing. Whilst the link between metabolic disorders and lipids seems to be clear, interpreting lipid regulation in the context of neuropsychiatric disorders is a new approach. Mental disorders account for almost 15% of the total global disease burden with Alzheimer's disease, depression or schizophrenia being amongst the most widespread mental disorders in the general population. For this reason rapid and early diagnosis is crucial and finding the right biomarkers is of great importance. Lipids appear to be essential in learning the aetiopathology of neuropsychiatric diseases as well as in biomarker research as they are most abundantly present in the brain. This study discusses recent findings in neuropsychiatry in the context of lipid analysis. PMID- 26351934 TI - Statistical methods used in the calculation of geriatric reference intervals: a systematic review. AB - BACKGROUND: Geriatric reference intervals (RIs) are not commonly available and are rarely used. It is difficult to select a reference population from a cohort with a high degree of morbidity. Also important are the statistical approaches used to determine health-associated reference values. It is the aim of this study to examine the statistical methods used in the calculation of geriatric RIs. METHODS: A search was conducted on EMBASE and Medline for articles between January 1989 and January 2014. Studies were selected if they: 1) were English primary articles; 2) performed a clinical chemistry test on a blood fraction; 3) had a population sub-group consisting of individuals >=65 years of age; and 4) calculated a RI for the subgroup >=65 years of age. RESULTS: There were 64 articles identified, of which 78.1% described the RI calculation method used. RI calculation was performed by non-parametric (21.9%), parametric (42.2%), robust (3.1%), or other (17.2%) methods. Outlier detection (SD, Grubb's test, Tukey's fence, Dixon) was infrequently used and although most studies performed partitioning, only 57.8% tested the statistical significance of the partitions. Few studies (17.2%) reported confidence intervals for the RI estimates. Overall, only 14.1% of studies provided RI estimates which followed the CLSI guideline EP28-A3c. CONCLUSIONS: Statistical methods for RI calculation and partitioning varied considerably between studies and many failed to provide adequate descriptions of these methods. Challenges in analyses arose from insufficient sample sizes and heterogeneity in the elderly population. Geriatric RIs, although present in the literature, may not be properly calculated and should be carefully considered before applying them for clinical care. PMID- 26351935 TI - Assessment of serum free light chain levels in healthy adults immediately after marathon running. AB - BACKGROUND: Immunoglobulin kappa and lambda free light chains (FLC) are important serum biomarkers for diagnosing and monitoring plasma cell dyscrasias (via the kappa:lambda FLC ratio), and assessing immune competence and activation status (via ?FLC). FLCs are produced, in excess of heavy chains, from healthy plasma cells during immunoglobulin production, but unlike intact immunoglobulins that are cleared by cellular catabolism over a number of weeks, FLC are rapidly cleared from the bloodstream by the renal glomerulus with a half-life of 3 (kappa FLC)-6 (lambda FLC) hours. Marathon running has been shown to acutely and transiently decrease renal function, however, the impact of prolonged aerobic exercise on FLC levels remains unknown. METHODS: We measured serum FLC levels in 60 runners before, and immediately after, the 2010 Eindhoven Marathon. RESULTS: A significant increase (p<0.01) in kappa FLC levels was observed after the marathon, and kappa FLC correlated positively with serum creatinine levels. No changes were observed for lambda FLC, and thus, there were subtle elevations in the ?FLC and FLC ratio in some participants. Indeed, we found that 13% of participants had an abnormally increased FLC ratio upon completion of the marathon; a phenomenon previously observed in renal diseases. CONCLUSIONS: Abnormal FLC ratios observed after exercise reflected an increase in serum kappa FLC levels, which may be due to acute and transient reductions in renal function during exercise, though we also observed an increase in serum IgG and IgA and thus cannot exclude exercise-induced immune stimulation or immunoglobulin redistribution. PMID- 26351936 TI - Liposomal interference on Sysmex XN-series body fluid mode. PMID- 26351938 TI - Between analyser differences in chloride measurements and thus anion gap cause different interpretations of the acid-base balance. PMID- 26351937 TI - mRNA overexpression of kallikrein-related peptidase 14 (KLK14) is an independent predictor of poor overall survival in chronic lymphocytic leukemia patients. AB - BACKGROUND: Tissue kallikrein and kallikrein-related peptidases (KLKs) compose a family of serine endopeptidases with much clinical interest in oncology, as their potential as diagnostic and/or prognostic molecular biomarkers in several human malignancies has already been evidenced. However, none of the members of this family has ever been studied in hematological malignancies. Based on our preliminary results regarding the differential mRNA expression of several KLK genes in peripheral blood mononuclear cells (PBMCs) of patients with chronic lymphocytic leukemia (CLL) compared to healthy blood donors, we decided to study the diagnostic and prognostic potential of KLK14 mRNA expression in CLL. METHODS: Total RNA was isolated from 69 CLL patients and 31 non-leukemic blood donors. After reverse transcription of poly(A)-RNA, KLK14 mRNA levels were quantified using a sensitive and accurate quantitative real-time PCR (qPCR) methodology. RESULTS: According to ROC analysis, KLK14 mRNA overexpression successfully discriminated CLL patients from normal population (area under the curve [AUC] 0.89, 95% confidence interval [CI] 0.83-0.95, p<0.001). Moreover, although not clearly related to clinical staging or other prognostic factors including IGHV mutational status and CD38 expression, strong KLK14 mRNA expression was shown to predict reduced overall survival of CLL patients (p=0.026) using Kaplan-Meier survival analysis. The unfavorable prognostic value of KLK14 mRNA overexpression in CLL patients' PBMCs was independent of established prognostic factors of the disease, as shown by multivariate Cox regression analysis (hazard ratio [HR] 14.65, 95% CI 1.81-118.36, p=0.012). CONCLUSIONS: KLK14 mRNA expression merits further investigation as a potential prognostic biomarker of overall survival of patients with CLL. PMID- 26351939 TI - Platelet microRNAs are not modulated by systemic heparin in acute coronary syndromes. PMID- 26351940 TI - Fetal exposure to ethanol: relationship between ethyl glucuronide in maternal hair during pregnancy and ethyl glucuronide in neonatal meconium. AB - BACKGROUND: In recent years, fatty acid ethyl esters (FAEEs) and ethyl glucuronide (EtG) in meconium emerged as reliable, direct biological markers for establishing gestational ethanol exposure. We investigated whether EtG in maternal hair measured during the three trimesters of pregnancy correlated with EtG and FAEEs in neonatal meconium. METHODS: In a prospective sample of 80 mother infant dyads from Barcelona (Spain), we measured EtG and FAEE in maternal hair segments and meconium samples using a validated UHPLC-MS/MS method. RESULTS: Fifty-eight (72.5%) women had EtG concentrations in the hair shafts >7 pg/mg in one or more pregnancy trimesters, and EtG and FAEEs in meconium samples were documented in 50 and 24 of their neonates, respectively. The best significant correlations (p<0.0001) were found between EtG concentration in the proximal 0-3 and 3-6 hair shaft segments corresponding to the last two pregnancy trimesters and EtG in neonatal meconium (rho=0.609 and rho=0.577, respectively). Using the combination of EtG in meconium >=30 ng/g and a median of EtG >11 pg/mg in maternal hair during the second and third trimesters of pregnancy, prenatal ethanol exposure could be predicted with a sensitivity of 85.7% and specificity of 73.7%. CONCLUSIONS: This study provides evidence of proven fetal exposure to ethanol during the second and third trimesters of pregnancy by linking detection of ethanol biomarkers (EtG) in maternal hair segments and EtG in neonatal meconium. PMID- 26351941 TI - Comparing the effect of isotopically labeled or structural analog internal standards on the performance of a LC-MS/MS method to determine ciclosporin A, everolimus, sirolimus and tacrolimus in whole blood. AB - BACKGROUND: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is routinely used for analysis of immunosuppressive drugs. This study investigated whether replacing analog internal standards (ANISs) with isotopically labeled internal standards (ILISs) has an impact on the performance of a LC-MS/MS method for the quantification of tacrolimus (TAC), sirolimus (SIR), ciclosporin A (CsA) and everolimus (EVE) in whole blood. METHODS: Following hemolysis, protein precipitation, and extraction with either ANISs (ascomycin, desmethoxy-rapamycin, CsD), or ILISs (TAC-13C,D2; SIR-13C,D3; CsA-D12; EVE-D4), samples were centrifuged and injected into a LC-MS/MS device equipped with a C18 reversed phase column. The effect of the two ISs on the linearity, precision, accuracy, trueness, matrix effects, and carryover was investigated by using the same patient-, proficiency testing-, and quality control samples. Statistical analysis of agreement between results includes a standard random effects model and Passing Bablok regression. RESULTS: Within-day imprecision was <10%, between-day <8%, and trueness 91%-110% for all the analytes with both ISs. No carryover or matrix effects were observed. The median accuracy was -2.1% for CsA, 9.1% for EVE, 12.2% for SIR, and -1.2% for TAC with the ILISs; and -2% for CsA, 9.8% for EVE, 11.4% for SIR, and 0.2% for TAC with the ANISs. Results of patient and proficiency testing samples were not statistically different. CONCLUSIONS: Although ILISs are generally considered superior to ANISs, they may not be always essential. When optimizing a LC-MS/MS method other factors must be also considered. PMID- 26351942 TI - Comparative evaluation of the Aptima HIV-1 Quant Dx assay and COBAS TaqMan HIV-1 v2.0 assay using the Roche High Pure System for the quantification of HIV-1 RNA in plasma. AB - BACKGROUND: Quantification of human immunodeficiency virus type 1 (HIV-1) RNA in plasma has become the standard of care in the management of HIV-infected patients. There are several commercially available assays that have been implemented for the detection of HIV-1 RNA in plasma. Here, the new Hologic Aptima(r) HIV-1 Quant Dx assay (Aptima HIV) was compared to the Roche COBAS(r) TaqMan(r) HIV-1 Test v2.0 for use with the High Pure System (HPS/CTM). METHODS: The performance characteristics of the assays were assessed using commercially available HIV reference panels, dilution of the WHO 3rd International HIV-1 RNA International Standard (WHO-IS) and plasma from clinical specimens. Assay performance was determined by linear regression, Deming correlation analysis and Bland-Altman analysis. RESULTS: Testing of HIV-1 reference panels revealed excellent agreement. The 61 clinical specimens quantified in both assays were linearly associated and strongly correlated. CONCLUSIONS: The Aptima HIV assay offers performance comparable to that of the HPS/CTM assay and, as it is run on a fully automated platform, a significantly improved workflow. PMID- 26351943 TI - Hyperuricemia as risk factor for coronary heart disease incidence and mortality in the general population: a systematic review and meta-analysis. AB - Previous meta-analyses reported no significant or weak association between hyperuricemia (HU) and coronary heart disease (CHD). We updated the literature search, systematically reviewing retrieved papers. The peer-reviewed literature published from 1965 to December 2014 was searched using Medline and Embase. We included prospective cohort studies involving adults (sample size >=100) with no cardiovascular disease (CVD) and a follow-up of at least 1 year. Studies were excluded if they considered as outcome the CVD incidence/mortality without separately reporting data on CHD, did not adjusted for major confounders and if the 95% confidence interval (CI) for risk ratio (RR) was not available. Relative risk or hazard ratio estimates, with the corresponding CIs, were obtained. For CHD incidence 12 populations were included (457,915 subjects [53.7% males]). For CHD mortality seven populations were included (237,433 subjects [66.3% males]). The overall combined RR were 1.206 (CI 1.066-1.364, p=0.003) for CHD incidence and 1.209 (CI 1.003-1.457, p=0.047) for CHD mortality, respectively. Subgroup analysis showed a marginal (incidence) and not significant (mortality) association between HU and CHD in men, but an increased risk for CHD incidence and mortality in hyperuricemic women (RR 1.446, CI 1.323-1.581, p<0.0001, and RR 1.830, CI 1.066-3.139, p=0.028, respectively). The risk markedly increases for urate concentrations >7.0 mg/dL. HU appears to increase the risk of CHD events in the general population, mainly in adult women. This finding requires, however, further investigation. PMID- 26351944 TI - Falsely elevated ferritin in patients with a high concentration of rheumatoid factor. PMID- 26351945 TI - International Normalized Ratio (INR) testing: analytical and clinical performance of four point-of-care devices versus central laboratory instrumentation analysis. PMID- 26351946 TI - Early prediction of gestational diabetes: a practical model combining clinical and biochemical markers. AB - BACKGROUND: Gestational diabetes (GDM) is usually diagnosed late in pregnancy, precluding early preventive interventions. This study aims to develop a predictive model based on clinical factors and selected biochemical markers for the early risk assessment of GDM. METHODS: Based on a prospective cohort of 7929 pregnant women from the Quebec City metropolitan area, a nested case-control study was performed including 264 women who developed GDM. Each woman who developed GDM was matched with two women with normal glycemic profile. Risk prediction models for GDM and GDM requiring insulin therapy were developed using multivariable logistic regression analyses, based on clinical characteristics and the measurement of three clinically validated biomarkers: glycated hemoglobin (HbA1c), sex hormone binding globulin (SHBG) and high-sensitivity C-reactive protein (hsCRP) measured between 14 and 17 weeks of gestation. RESULTS: HbA1c and hsCRP were higher and SHBG was lower in women who developed GDM (p<0.001). The selected model for the prediction of GDM, based on HbA1c, SHBG, BMI, past history of GDM, family history of diabetes and soft drink intake before pregnancy yielded an area under the ROC curve (AUC) of 0.79 (0.75-0.83). For the prediction of GDM requiring insulin therapy, the selected model including the same six variables yielded an AUC of 0.88 (0.84-0.92) and a sensitivity of 68.9% at a false-positive rate of 10%. CONCLUSIONS: A simple model based on clinical characteristics and biomarkers available early in pregnancy could allow the identification of women at risk of developing GDM, especially GDM requiring insulin therapy. PMID- 26351947 TI - Capillary electrophoresis for the screening and diagnosis of inherited hemoglobin disorders. Ready for prime time? PMID- 26351948 TI - Long-term stability of glucose: 96-h study using Terumo Glycaemia tubes. AB - BACKGROUND: Long transportation times of samples can occur due to centralization of laboratories, and also in, for instance epidemiological multicenter studies with one core laboratory. Unsatisfactory glycolysis inhibition is known to threaten the correct measurements of glucose concentration in patient samples. In former studies Terumo Glycaemia tubes proved to be superior to other anticoagulant systems for time periods of up to 24 h. We investigated long-term stability of glucose concentration in Terumo Glycaemia tubes for up to 96 h at room temperature and imitated transport conditions by continuous sample shaking. METHODS: Human venous blood samples were collected from 40 healthy blood donors using Terumo Glycaemia tubes. Immediately after sampling, tubes were mixed according to the manufactures recommendations. To simulate transportation conditions samples were placed on a shaker for the entire study period and maintained at room temperature. Samples were (re)centrifuged at 0, 24, 36, 48, 72 and 96 h prior to measuring glucose concentration. The glucose concentration at 0 h was used as baseline for evaluation of long-term stability. RESULTS: The recovery of glucose was 100% throughout the study, including the 96-h measurements. Deviations of single glucose measurements were within the imprecision of the measurement procedure. CONCLUSIONS: Terumo Glycaemia tubes can effectively stabilize glucose in whole blood samples kept at room temperature on a shaker during a 96-h time period. Therefore, we consider Terumo Glycaemia tubes as a suitable glucose stabilizing tube for long intervals between sample collection and glucose quantification. PMID- 26351949 TI - More on the accuracy of the Architect enzymatic assay for hemoglobin A1c and its traceability to the IFCC reference system. PMID- 26351950 TI - A rare and unstable hemoglobin variant, Hb M Dothan beta 25/26 (-GTG), detected by the anomalous cytogram on Sysmex XE-2100. PMID- 26351951 TI - Hb Hope [beta136Gly->Asp] and Hb Grady [alpha119_120insGluPheThr] compound heterozygosity in a Mauritanian patient. PMID- 26351952 TI - Comparison of the Elecsys calcitonin assay with the Immulite 1000 assay. Describing one case with heterophilic antibody interference. PMID- 26351953 TI - Susceptibility of commonly used ferritin assays to the classic hook effect. PMID- 26351954 TI - Development of an immunomagnetic beads-based test and its application in influenza surveillance. PMID- 26351955 TI - How to report results of prothrombin and activated partial thromboplastin times. AB - Prothrombin time (PT) and activated partial thromboplastin time (APTT) are the most widely used tests to investigate coagulation abnormalities. Varied result reporting have been introduced over the years for the two tests, thus making their interpretation rather confusing in different clinical settings. PT results have been reported as clotting time, percentage activity, PT-ratio (patient-to normal clotting time) and as international normalized ratio (INR). The INR scale has been devised to harmonize results stemming from different thromboplastins from patients on treatment with vitamin K antagonists. Therefore, there are some theoretical and evidence-based considerations that make the INR formally invalid when the test is used to analyze patients in other clinical settings. Unfortunately, this limitation has been frequently overlooked, and the INR has been (and is currently) used as a universal system of results harmonization. The APTT has been historically reported as clotting time or as ratio (patient-to normal clotting time). In this opinion paper we review the current state-of-the art for result reporting and attempt to give practical guidance on how PT and APTT should be reported in different clinical conditions for which the tests are requested. PMID- 26351956 TI - External Quality Assessment Programs in the US with an emphasis on urinary sediment testing: the College of American Pathologists experience. AB - The College of American Pathologists (CAP) has maintained the highest standards for laboratory medicine through education, evaluation, and certification. One form of External Quality Assurance - proficiency testing (PT) - is the centerpiece of that mission. Over 500 medical and scientific experts oversee CAP PT programs which include more than 600 tests performed by 22,000 laboratories in over 100 countries. It is the most comprehensive laboratory peer-review comparison program in the world. The CAP offers four urine sediment PT products tailored to the needs of different laboratories. Each includes three or four digital images, shipped twice a year. The program is overseen by the Hematology and Clinical Microscopy Resource Committee. Images are graded if there is 80% or greater consensus of either referee or participant laboratories. Failing laboratories must analyze the reasons for the failure, report the results, and initiate corrective action. Over the years, there has been a progressive decline in the number of errors, demonstrating that education and regulatory oversight are major contributors to improved PT performance and, by extension, patient care. The PT urine sediment image databank is a unique resource, representing the consensus of many laboratories. Participant and referee responses identify which morphologic variants are unambiguous and which are more difficult to classify. The PT challenges include discussions of disease pathophysiology and key morphologic features. This teaching component is what helps to set the CAP's program apart. The discussions formed the basis for the Color Atlas of Urinary Sediment published by the CAP in 2010. PMID- 26351957 TI - Fetal sex discordance between sequencing-based and real-time PCR non-invasive prenatal test due to a vanishing twin. PMID- 26351958 TI - Laboratory medicine does matter in science (and medicine)... yet many seem to ignore it. PMID- 26351959 TI - Obesity and fertility. AB - The prevalence of overweight and obesity in women of reproductive age has increased over the past 30 years. Infertility affects 1 in 7 couples, and female obesity is associated with anovulation. The mechanisms by which excessive fat delays time to pregnancy (TTP) appear rooted in ovulatory problems and direct effects on oocytes, causing poorer embryo development, as well as in effects on the endometrium. Weight loss in women has been shown to improve conception, but not necessarily live birth rates following fertility treatment, and further research in this area is needed. The obesity epidemic has been accompanied by a potential rise in male infertility, which has been attributed to hormonal disturbances and compromised semen parameters. PMID- 26351960 TI - Maternal and fetal lipid metabolism under normal and gestational diabetic conditions. AB - Maternal lipids are strong determinants of fetal fat mass. Here we review the overall lipid metabolism in normal and gestational diabetes mellitus (GDM) pregnancies. During early pregnancy, the increase in maternal fat depots is facilitated by insulin, followed by increased adipose tissue breakdown and subsequent hypertriglyceridemia, mainly as a result of insulin resistance (IR) and estrogen effects. The response to diabetes is variable as a result of greater IR but decreased estrogen levels. The vast majority of fatty acids (FAs) in the maternal circulation are esterified and associated with lipoproteins. These are taken up by the placenta and hydrolyzed by lipases. The released FAs enter various metabolic routes and are released into fetal circulation. Although these determinants are modified in maternal GDM, the fetus does not seem to receive more FAs than in non-GDM pregnancies. Long-chain polyunsaturated FAs are essential for fetal development and are obtained from the mother. Mitochondrial FA oxidation occurs in fetal tissue and in placenta and contributes to energy production. Fetal fat accretion during the last weeks of gestation occurs very rapidly and is sustained not only by FAs crossing the placenta, but also by fetal lipogenesis. Fetal hyperinsulinemia in GDM mothers promotes excess accretion of adipose tissue, which gives rise to altered adipocytokine profiles. Fetal lipoproteins are low at birth, but the GDM effects are unclear. The increase in body fat in neonates of GDM women is a risk factor for obesity in early childhood and later life. PMID- 26351961 TI - A post-hoc Unweighted Analysis of Counter-Matched Case-Control Data. AB - Informative sampling based on counter-matching risk set subjects on exposure correlated with a variable of interest has been shown to be an efficient alternative to simple random sampling; however, the opposite is true when correlation between the two covariates is absent. Thus, the counter-matching design will entail substantial gains in statistical efficiency compared to simple random sampling at a first stage of analyses focused by design on variables correlated with the counter-matching variable but will lose efficiency at a second stage of analyses aimed at variables independent of the counter-matching variable and not conceived as a part of the initial study. In an effort to recover efficiency in such second stage of analyses scenarios, we considered a naive analysis of the effect of a dichotomous covariate on the disease rates in the population that ignores the underlying counter-matching sampling design. We derive analytical expressions for the bias and variance and show that when the counter-matching and the new dichotomous variable of interest are uncorrelated and a multiplicative main effects model holds, such an analysis is advantageous over the standard "weighted" approach, especially when the counter-matching variable is rare and in such scenarios the efficiency gains exceeds 80%. Moreover, we consider all possible conceptual violations of the required assumptions and show that moderate departures from the above-mentioned requirements lead to negligible levels of bias; numerical values for the bias under common scenarios are provided. The method is illustrated via an analysis of BRCA1/2 deleterious mutations in the radiation treatment counter-matched WECARE study of second breast cancer. PMID- 26351962 TI - Fluvoxamine-associated oscillopsia and a role for personalized medication dosing. AB - A 60-year-old woman reported horizontal "shimmering" movement while reading crossword puzzles when using fluvoxamine, bupropion, quetiapine, lithium, and levothyroxine. This visual disturbance, likely oscillopsia, started after the fluvoxamine was added and waned as the fluvoxamine was tapered, disappearing after the drug was discontinued. Genetic testing to explore how the patient metabolizes these medications combined with YouScript(r) interaction analysis suggest that she may have had abnormally high plasma concentrations of fluvoxamine during this time. Oscillopsia may be a novel dose-dependent side effect of fluvoxamine. Genetic testing combined with YouScript has the potential to discover novel drug side effects, elucidate drug interactions and guide future prescribing decisions. PMID- 26351964 TI - Native language change during early stages of second language learning. AB - Research on proficient bilinguals has demonstrated that both languages are always active, even when only one is required. The coactivation of the two languages creates both competition and convergence, facilitating the processing of cognate words, but slowing lexical access when there is a requirement to engage control mechanisms to select the target language. Critically, these consequences are evident in the native language (L1) as well as in the second language (L2). The present study questioned whether L1 changes can be detected at early stages of L2 learning and how they are modulated by L2 proficiency. Native English speakers learning Spanish performed an English (L1) lexical decision task that included cognates while event-related potentials were recorded. They also performed verbal fluency, working memory, and inhibitory control tasks. A group of matched monolinguals performed the same tasks in English only. The results revealed that intermediate learners demonstrate a reduced N400 for cognates compared with noncognates in English (L1), and an emerging effect is visually present in beginning learners as well; however, no behavioral cognate effect was present for either group. In addition, slower reaction times in English (L1) are related to a larger cognate N400 magnitude in English (L1) and Spanish (L2), and to better inhibitory control for learners but not for monolinguals. The results suggest that contrary to the claim that L2 affects L1 only when L2 speakers are highly proficient, L2 learning begins to impact L1 early in the development of the L2 skill. PMID- 26351965 TI - Direct current stimulation of the left temporoparietal junction modulates dynamic humor appreciation. AB - The aim of this study was to evaluate the influence of transcranial direct current stimulation targeting the left temporoparietal junction (TPJ) on humor appreciation during a dynamic video rating task. In a within-participants design, we targeted the left TPJ with anodal, cathodal, or no transcranial direct current stimulation, centered at electrode site C3 using a 4*1 targeted stimulation montage. During stimulation, participants dynamically rated a series of six stand up comedy videos for perceived humor. We measured event-related (time-locked to crowd laughter) modulation of humor ratings as a function of stimulation condition. Results showed decreases in rated humor during anodal (vs. cathodal or none) stimulation; this pattern was evident for the majority of videos and was only partially predicted by individual differences in humor style. We discuss the possibility that upregulation of neural circuits involved in the theory of mind and empathizing with others may reduce appreciation of aggressive humor. In conclusion, the present data show that neuromodulation of the TPJ can alter the mental processes underlying humor appreciation, suggesting critical involvement of this cortical region in detecting, comprehending, and appreciating humor. PMID- 26351966 TI - Radical Initiated Hydrosilylation on Silicon Nanocrystal Surfaces: An Evaluation of Functional Group Tolerance and Mechanistic Study. AB - Hydrosilylation is among the most common methods used for modifying silicon surface chemistry. It provides a wide range of surface functionalities and effective passivation of surface sites. Herein, we report a systematic study of radical initiated hydrosilylation of silicon nanocrystal (SiNC) surfaces using two common radical initiators (i.e., 2,2'-azobis(2-methylpropionitrile) and benzoyl peroxide). Compared to other widely applied hydrosilylation methods (e.g., thermal, photochemical, and catalytic), the radical initiator based approach is particle size independent, requires comparatively low reaction temperatures, and yields monolayer surface passivation after short reaction times. The effects of differing functional groups (i.e., alkene, alkyne, carboxylic acid, and ester) on the radical initiated hydrosilylation are also explored. The results indicate functionalization occurs and results in the formation of monolayer passivated surfaces. PMID- 26351968 TI - Usefulness of Conventional Transbronchial Needle Aspiration for Sampling of Mediastinal Lymph Nodes in Lung Cancer. AB - BACKGROUND: Transbronchial needle aspiration (TBNA) is recognized as a valuable tool for the sampling of mediastinal lymph nodes. In this study, we report data about the diagnostic yield of conventional TBNA in the diagnosis and staging of lung cancer. METHODS: All patients with suspected lung cancer who underwent bronchoscopy with conventional TBNA in the years 2008 to 2012 were evaluated. TBNA was performed on mediastinal lymph nodes enlarged at chest computed tomography scan and/or with increased fluorodeoxyglucose uptake on positron emission tomography/computed tomography scan. Cytologic results derived from TBNA have been compared, with the final diagnosis obtained with other more invasive procedures and/or with a clinical-radiologic follow-up of at least 12 months. RESULTS: TBNA was performed on 375 patients. However, 19 patients were lost to follow-up, and data from 356 patients with a total 459 TBNA specimens were analyzed. TBNA was positive for metastatic involvement of lymph nodes in 172 of 282 patients with cancer, with a sensitivity of 61%. Sensitivity achieved 65% when we considered the total of 459 TBNA specimens. The overall diagnostic accuracy of TBNA was 69%. The nodal stations more frequently examined were 7 (subcarinal: 190 TBNAs), 4R (right lower paratracheal: 147 TBNAs), and 10R (right hilar: 76 TBNAs), with a sensitivity of 66%, 66%, and 67%, respectively. CONCLUSION: Conventional TBNA remains a useful method for the diagnosis and staging of lung cancer, with a good diagnostic yield in several nodal stations. PMID- 26351970 TI - Divergent Total Syntheses of Rhodomyrtosones A and B. AB - Herein, we report total syntheses of the tetramethyldihydroxanthene natural product rhodomyrtosone B and the related bis-furan beta-triketone natural product rhodomyrtosone A. Nickel-(II)-catalyzed 1,4-conjugate addition of an alpha alkylidene-beta-dicarbonyl substrate was developed to access the congener rhodomyrtosone B, and oxygenation of the same monoalkylidene derivative followed by cyclization was employed to obtain the bis-furan natural product rhodomyrtosone A. PMID- 26351969 TI - Symptom-Onset Dosing of Sertraline for the Treatment of Premenstrual Dysphoric Disorder: A Randomized Clinical Trial. AB - IMPORTANCE: Serotonin reuptake inhibitors (SRIs) are efficacious treatments for premenstrual dysphoric disorder (PMDD) when given daily or for half of the menstrual cycle during the luteal phase. Preliminary studies suggest that SRI treatment can be shortened to the interval from symptom onset through the beginning of menses. OBJECTIVE: To determine the efficacy of symptom-onset dosing with the SRI sertraline hydrochloride for treatment of PMDD. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, placebo-controlled, multisite, parallel-group randomized clinical trial conducted September 1, 2007, to February 29, 2012, at 3 university medical centers. In all, 252 women with PMDD started treatment at symptom onset and continued until the first few days of menses for 6 menstrual cycles. Intent-to-treat analyses were performed February 28, 2014, through April 21, 2015. INTERVENTIONS: Placebo or sertraline hydrochloride, 50 to 100 mg/d, during the symptomatic interval. MAIN OUTCOMES AND MEASURES: Premenstrual Tension Scale (PMTS) score was the primary outcome measure (score range, 0-36; 36 indicates most severe score). Secondary outcome measures included the Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C) (score range, 0-84; 84 indicates most severe score), Daily Record of Severity of Problems (DRSP) (total and subscale scores; higher scores indicate most severe problems), Clinical Global Impression (CGI) scales (score range, 1-7; 7 indicates most severe symptoms and least improvement), and Michelson SSRI (Selective SRI) Withdrawal Symptoms Scale scores (range, 0-51; higher scores indicate more severe withdrawal symptoms). RESULTS: Among the participants, 125 with PMDD were randomized to sertraline, and 127 to placebo. At baseline the mean (SD) PMTS scores for sertaline and placebo were 22.3 (4.8) and 21.4 (4.5), respectively, which declined to 11.7 (6.8) and 12.0 (6.9), respectively; group mean difference, 1.88 (95% CI, 0.01-3.75; P = .06). The mean (SD) estimated difference in IDS-C scores between baseline (35.4 [10.7] for sertraline; 32.8 [10.4] for placebo) and the end point (15.3 [10.7] for sertraline; 17.8 [11.0] for placebo) favored the sertraline group by 5.14 (95% CI, 1.97-8.31) points (P = .02). Compared with the placebo group, those assigned to sertraline showed greater improvement on the total DRSP score (estimated mean difference, 1.09 [95% CI, 0.96-1.25] points; P = .02) and Anger/Irritability DRSP subscale score (1.22 [95% CI, 1.05-1.41] points; P < .01) and were more likely to respond to treatment (77 of 115 patients [67.0%] for sertraline and 65 of 124 [52.4%] for placebo; chi21 = 5.23; P = .02). The mean (SD) number of symptomatic days before treatment diminished over time (sertraline, -0.7 [3.4] days; placebo, -1.0 [3.2] days), with no group differences in symptomatic days or the Michelson SSRI Withdrawal Symptoms Scale. CONCLUSIONS AND RELEVANCE: Depending on the symptom scale, women with PMDD may or may not benefit from SRI treatment during the interval from the onset of premenstrual symptoms through the first few days of menses. Abrupt treatment cessation was not associated with discontinuation symptoms. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00536198. PMID- 26351973 TI - Clinical Trials in Physical Medicine and Rehabilitation. PMID- 26351971 TI - Intratracheal Administration of Budesonide/Surfactant to Prevent Bronchopulmonary Dysplasia. AB - RATIONALE: Bronchopulmonary dysplasia (BPD) is an important complication of mechanical ventilation in preterm infants, and no definite therapy can eliminate this complication. Pulmonary inflammation plays a crucial role in its pathogenesis, and glucocorticoid is one potential therapy to prevent BPD. OBJECTIVES: To compare the effect of intratracheal administration of surfactant/budesonide with that of surfactant alone on the incidence of death or BPD. METHODS: A clinical trial was conducted in three tertiary neonatal centers in the United States and Taiwan, in which 265 very-low-birth-weight infants with severe respiratory distress syndrome who required mechanical ventilation and inspired oxygen (fraction of inspired oxygen, >=50%) within 4 hours of birth were randomly assigned to one of two groups (131 intervention and 134 control). The intervention infants received surfactant (100 mg/kg) and budesonide (0.25 mg/kg), and the control infants received surfactant only (100 mg/kg), until each infant required inspired O2 at less than 30% or was extubated. MEASUREMENTS AND MAIN RESULTS: The intervention group had a significantly lower incidence of BPD or death (55 of 131 [42.0%] vs. 89 of 134 [66%]; risk ratio, 0.58; 95% confidence interval, 0.44-0.77; P < 0.001; number needed to treat, 4.1; 95% confidence interval, 2.8-7.8). The intervention group required significantly fewer doses of surfactant than did the control group. The intervention group had significantly lower interleukin levels (IL-1, IL-6, IL-8) in tracheal aspirates at 12 hours and lower IL-8 at 3-5 and 7-8 days. CONCLUSIONS: In very-low-birth-weight infants with severe respiratory distress syndrome, intratracheal administration of surfactant/budesonide compared with surfactant alone significantly decreased the incidence of BPD or death without immediate adverse effect. Clinical trial registered with www.clinicaltrials.gov (NCT-00883532). PMID- 26351974 TI - How to manage patients on rivaroxaban in the emergency department: a statement of the Italian society of emergency medicine advisory board. AB - Rivaroxaban, a new oral anticoagulant, has been approved in many countries and its everyday use in clinical practice is increasing. Thus, the chances for an emergency physician to encounter rivaroxaban-treated patients in emergency situations have increased. Here, the authors address the main issues in terms of the prescription of rivaroxaban and the management of these patients in cases of minor or major bleeding, urgent surgery, atrial fibrillation requiring cardioversion, acute ischemic stroke, ST-elevation myocardial infarction, and new onset of atrial fibrillation in recent ST-elevation myocardial infarction. The recommendations reached are based on a literature review and a panel discussion of the advisory board of SIMEU, the Italian Society of Emergency Medicine. PMID- 26351975 TI - Hemostatic dressings in civil prehospital practice: 30 uses of QuikClot Combat Gauze. AB - To report the use and describe the interest of hemostatic dressings in a civilian setting, we provided medical prehospital teams with QuikClot Combat Gauze (QCG) and asked physicians to complete a specific questionnaire after each use. Thirty uses were prospectively reported. The wounds were mostly caused by cold steel (n=15) and were primarily cervicocephalic (n=16), with 19/30 active arterial bleedings. For 26/30 uses, hemostatic dressing was justified by the inefficiency of other hemostasis techniques. Those 30 applications were associated with 22 complete cessations of bleeding, six decreases of bleeding, and ineffectiveness in two cases. The application of QCG permitted the removal of an effective tourniquet that was applied initially for three patients. No side-effects were reported. The provision of hemostatic dressings in civilian resuscitation ambulances was useful by providing an additional tool to limit bleeding while rapidly transporting the injured patient to a surgical facility. PMID- 26351976 TI - GYM score: 30-day mortality predictive model in elderly patients attended in the emergency department with infection. AB - OBJECTIVE: To determine the validity of the classic sepsis criteria or systemic inflammatory response syndrome (heart rate, respiratory rate, temperature, and leukocyte count) and the modified sepsis criteria (systemic inflammatory response syndrome criteria plus glycemia and altered mental status), and the validity of each of these variables individually to predict 30-day mortality, as well as develop a predictive model of 30-day mortality in elderly patients attended for infection in emergency departments (ED). METHODS: A prospective cohort study including patients at least 75 years old attended in three Spanish university ED for infection during 2013 was carried out. Demographic variables and data on comorbidities, functional status, hemodynamic sepsis diagnosis variables, site of infection, and 30-day mortality were collected. RESULTS: A total of 293 patients were finally included, mean age 84.0 (SD 5.5) years, and 158 (53.9%) were men. Overall, 185 patients (64%) fulfilled the classic sepsis criteria and 224 patients (76.5%) fulfilled the modified sepsis criteria. The all-cause 30-day mortality was 13.0%. The area under the curve of the classic sepsis criteria was 0.585 [95% confidence interval (CI) 0.488-0.681; P=0.106], 0.594 for modified sepsis criteria (95% CI: 0.502-0.685; P=0.075), and 0.751 (95% CI: 0.660-0.841; P<0.001) for the GYM score (Glasgow <15; tachYpnea>20 bpm; Morbidity-Charlson index >=3) to predict 30-day mortality, with statistically significant differences (P=0.004 and P<0.001, respectively). The GYM score showed good calibration after bootstrap correction, with an area under the curve of 0.710 (95% CI: 0.605-0.815). CONCLUSION: The GYM score showed better capacity than the classic and the modified sepsis criteria to predict 30-day mortality in elderly patients attended for infection in the ED. PMID- 26351977 TI - Complications After Surgery for Stress Urinary Incontinence: Untangling a Mesh of Uncertainties. PMID- 26351978 TI - An Unusual 2-Tone Epidermal Cyst: Dermoscopy, Confocal Microscopy, and Histopathologic Correlations. PMID- 26351979 TI - Combined experimental and computational NMR study of crystalline and amorphous zeolitic imidazolate frameworks. AB - Zeolitic imidazolate frameworks (ZIFs) have attracted great interest in recent years due to their high chemical and thermal stability with promising applications in gas storage and separations. We investigate the structures of three different crystalline ZIFs - ZIF-4, ZIF-8, ZIF-zni - and their amorphous counterparts using high field (13)C and (15)N CP MAS NMR. The high field (20 T) allows for the observation of all crystallographically independent carbon and nitrogen atoms in the crystalline ZIFs. Combining our experimental results with density functional theory calculations enabled the assignment of all chemical shifts. The crystalline spectra reveal the potential of high field NMR to distinguish between two ZIF polymorphs, ZIF-4 and ZIF-zni, with identical [Zn(C3H3N2)2] chemical compositions. (13)C and (15)N CP MAS NMR data obtained for the amorphous ZIFs clearly showed signal broadening upon amorphization, confirming the retention of chemical composition and the structural similarity of amorphous ZIF-4 and ZIF-zni. In the case of amorphous ZIF-8, we present evidence for the partial de-coordination of the 2-methyl imidazole linker. PMID- 26351980 TI - Structure investigations on oxygen fluorides. AB - The crystal structure of O2F2 is obtained at -180 degrees C. In the solid state the molecule has the typical hydrogen peroxide structure that has been established long ago by electron diffraction and microwave spectroscopy. OF2 melts at -223.8 degrees C, so its structure is determined by powder X-ray data. The structure differs from the solid state structures of ozone and Br2O. O2F in its dissolved form as O2(+) HnFn+1(-) oxidizes palladium to the four valence state, as found some time ago. The first product formed at low temperatures is (O2(+)H3Pd2F12(-))n. PMID- 26351981 TI - Echocardiographic Predictors of Worse Outcome After Cardiac Resynchronization Therapy. AB - BACKGROUND: Cardiac resynchronization therapy (CRT) is the recommended treatment by leading global guidelines. However, 30%-40% of selected patients are non responders. OBJECTIVE: To develop an echocardiographic model to predict cardiac death or transplantation (Tx) 1 year after CRT. METHOD: Observational, prospective study, with the inclusion of 116 patients, aged 64.89 +/- 11.18 years, 69.8% male, 68,1% in NYHA FC III and 31,9% in FC IV, 71.55% with left bundle-branch block, and median ejection fraction (EF) of 29%. Evaluations were made in the pre-implantation period and 6-12 months after that, and correlated with cardiac mortality/Tx at the end of follow-up. Cox and logistic regression analyses were performed with ROC and Kaplan-Meier curves. The model was internally validated by bootstrapping. RESULTS: There were 29 (25%) deaths/Tx during follow-up of 34.09 +/- 17.9 months. Cardiac mortality/Tx was 16.3%. In the multivariate Cox model, EF < 30%, grade III/IV diastolic dysfunction and grade III mitral regurgitation at 6-12 months were independently related to increased cardiac mortality or Tx, with hazard ratios of 3.1, 4.63 and 7.11, respectively. The area under the ROC curve was 0.78. CONCLUSION: EF lower than 30%, severe diastolic dysfunction and severe mitral regurgitation indicate poor prognosis 1 year after CRT. The combination of two of those variables indicate the need for other treatment options. PMID- 26351982 TI - Does Ad Hoc Coronary Intervention Reduce Radiation Exposure? - Analysis of 568 Patients. AB - BACKGROUND: Advantages and disadvantages of ad hoc percutaneous coronary intervention have been described. However little is known about the radiation exposure of that procedure as compared with the staged intervention. OBJECTIVE: To compare the radiation dose of the ad hoc percutaneous coronary intervention with that of the staged procedureMethods:The dose-area product and total Kerma were measured, and the doses of the diagnostic and therapeutic procedures were added. In addition, total fluoroscopic time and number of acquisitions were evaluated. RESULTS: A total of 568 consecutive patients were treated with ad hoc percutaneous coronary intervention (n = 320) or staged percutaneous coronary intervention (n = 248). On admission, the ad hoc group had less hypertension (74.1% vs 81.9%; p = 0.035), dyslipidemia (57.8% vs. 67.7%; p = 0.02) and three vessel disease (38.8% vs. 50.4%; p = 0.015). The ad hoc group was exposed to significantly lower radiation doses, even after baseline characteristic adjustment between both groups. The ad hoc group was exposed to a total dose-area product of 119.7 +/- 70.7 Gycm2, while the staged group, to 139.2 +/- 75.3 Gycm2 (p < 0.001). CONCLUSION: Ad hoc percutaneous coronary intervention reduced radiation exposure as compared with diagnostic and therapeutic procedures performed at two separate times. PMID- 26351983 TI - Predictors of Arrhythmic Events Detected by Implantable Loop Recorders in Renal Transplant Candidates. AB - BACKGROUND: The recording of arrhythmic events (AE) in renal transplant candidates (RTCs) undergoing dialysis is limited by conventional electrocardiography. However, continuous cardiac rhythm monitoring seems to be more appropriate due to automatic detection of arrhythmia, but this method has not been used. OBJECTIVE: We aimed to investigate the incidence and predictors of AE in RTCs using an implantable loop recorder (ILR). METHODS: A prospective observational study conducted from June 2009 to January 2011 included 100 consecutive ambulatory RTCs who underwent ILR and were followed-up for at least 1 year. Multivariate logistic regression was applied to define predictors of AE. RESULTS: During a mean follow-up of 424 +/- 127 days, AE could be detected in 98% of patients, and 92% had more than one type of arrhythmia, with most considered potentially not serious. Sustained atrial tachycardia and atrial fibrillation occurred in 7% and 13% of patients, respectively, and bradyarrhythmia and non sustained or sustained ventricular tachycardia (VT) occurred in 25% and 57%, respectively. There were 18 deaths, of which 7 were sudden cardiac events: 3 bradyarrhythmias, 1 ventricular fibrillation, 1 myocardial infarction, and 2 undetermined. The presence of a long QTc (odds ratio [OR] = 7.28; 95% confidence interval [CI], 2.01-26.35; p = 0.002), and the duration of the PR interval (OR = 1.05; 95% CI, 1.02-1.08; p < 0.001) were independently associated with bradyarrhythmias. Left ventricular dilatation (LVD) was independently associated with non-sustained VT (OR = 2.83; 95% CI, 1.01-7.96; p = 0.041). CONCLUSIONS: In medium-term follow-up of RTCs, ILR helped detect a high incidence of AE, most of which did not have clinical relevance. The PR interval and presence of long QTc were predictive of bradyarrhythmias, whereas LVD was predictive of non-sustained VT. PMID- 26351984 TI - Human Tissue Kallikrein Activity in Angiographically Documented Chronic Stable Coronary Artery Disease. AB - BACKGROUND: Human tissue kallikrein (hK1) is a key enzyme in the kallikrein-kinin system (KKS). hK1-specific amidase activity is reduced in urine samples from hypertensive and heart failure (HF) patients. The pathophysiologic role of hK1 in coronary artery disease (CAD) remains unclear. OBJECTIVE: To evaluate hK1 specific amidase activity in the urine of CAD patientsMethods:Sixty-five individuals (18-75 years) who underwent cardiac catheterism (CATH) were included. Random midstream urine samples were collected immediately before CATH. Patients were classified in two groups according to the presence of coronary lesions: CAD (43 patients) and non-CAD (22 patients). hK1 amidase activity was estimated using the chromogenic substrate D-Val-Leu-Arg-Nan. Creatinine was determined using Jaffe's method. Urinary hK1-specific amidase activity was expressed as uM/(min . mg creatinine) to correct for differences in urine flow rates. RESULTS: Urinary hK1-specific amidase activity levels were similar between CAD [0.146 uM/(min .mg creatinine)] and non-CAD [0.189 uM/(min . mg creatinine)] patients (p = 0.803) and remained similar to values previously reported for hypertensive patients [0.210 uM/(min . mg creatinine)] and HF patients [0.104 uM/(min . mg creatinine)]. CAD severity and hypertension were not observed to significantly affect urinary hK1-specific amidase activity. CONCLUSION: CAD patients had low levels of urinary hK1-specific amidase activity, suggesting that renal KKS activity may be reduced in patients with this disease. PMID- 26351985 TI - Frequency of Cardiovascular Involvement in Familial Amyloidotic Polyneuropathy in Brazilian Patients. AB - BACKGROUND: Familial amyloidotic polyneuropathy (FAP) is a rare disease diagnosed in Brazil and worldwide. The frequency of cardiovascular involvement in Brazilian FAP patients is unknown. OBJECTIVE: Detect the frequency of cardiovascular involvement and correlate the cardiovascular findings with the modified polyneuropathy disability (PND) score. METHODS: In a national reference center, 51 patients were evaluated with clinical examination, electrocardiography (ECG), echocardiography (ECHO), and 24-hour Holter. Patients were classified according to the modified PND score and divided into groups: PND 0, PND I, PND II, and PND > II (which included PND IIIa, IIIb, and IV). We chose the classification tree as the statistical method to analyze the association between findings in cardiac tests with the neurological classification (PND). RESULTS: ECG abnormalities were present in almost 2/3 of the FAP patients, whereas ECHO abnormalities occurred in around 1/3 of them. All patients with abnormal ECHO also had abnormal ECG, but the opposite did not apply. The classification tree identified ECG and ECHO as relevant variables (p < 0.001 and p = 0.08, respectively). The probability of a patient to be allocated to the PND 0 group when having a normal ECG was over 80%. When both ECG and ECHO were abnormal, this probability was null. CONCLUSIONS: Brazilian patients with FAP have frequent ECG abnormalities. ECG is an appropriate test to discriminate asymptomatic carriers of the mutation from those who develop the disease, whereas ECHO contributes to this discrimination. PMID- 26351986 TI - Electrochemical Tip-Enhanced Raman Spectroscopy. AB - Interfacial properties are highly important to the performance of some energy related systems. The in-depth understanding of the interface requires highly sensitive in situ techniques that can provide fingerprint molecular information at nanometer resolution. We developed an electrochemical tip-enhanced Raman spectroscopy (EC-TERS) by introduction of the light horizontally to the EC-STM cell to minimize the optical distortion and to keep the TERS measurement under a well-controlled condition. We obtained potential-dependent EC-TERS from the adsorbed aromatic molecule on a Au(111) surface and observed a substantial change in the molecule configuration with potential as a result of the protonation and deprotonation of the molecule. Such a change was not observable in EC-SERS (surface-enhanced), indicating EC-TERS can more faithfully reflect the fine interfacial structure than EC-SERS. This work will open a new era for using EC TERS as an important nanospectroscopy tool for the molecular level and nanoscale analysis of some important electrochemical systems including solar cells, lithium ion batteries, fuel cells, and corrosion. PMID- 26351987 TI - B(C6F5)3: A New Class of Strong and Bulky Lewis Acid for Exo-Selective Intermolecular Diels-Alder Reactions of Unreactive Acyclic Dienes with alpha,beta Enals. AB - Lewis acid B(C6F5)3 catalyzed the Diels-Alder reactions of multisubstituted open chain dienes and alpha,beta-enals to afford the desired products with high exo selectivities are reported. The substituent effect of the dienes and dienophiles on the product's stereoselectivity was thoroughly investigated, and it was found that most of the desired exo-Diels-Alder products could be obtained in good yields and with high exo-stereoselectivities. PMID- 26351988 TI - The role of sentinel lymph nodes in endometrial and cervical cancer. AB - Sentinel lymph node assessment aims to determine lymphatic spread while preventing unnecessary interventions and morbidity for those who will not benefit from lymphadenectomy. All detection methods have demonstrated reasonable sensitivity with a low false negative rate and high negative predictive value; as long as the surgeon removes all enlarged lymph nodes and a site-specific lymphadenectomy is performed if there is no mapping. The significance of micrometastases and long term outcomes are yet to be determined. PMID- 26351989 TI - Shared and Distinct Neuroanatomic Regions Critical for Tool-related Action Production and Recognition: Evidence from 131 Left-hemisphere Stroke Patients. AB - The inferior frontal gyrus and inferior parietal lobe have been characterized as human homologues of the monkey "mirror neuron" system, critical for both action production (AP) and action recognition (AR). However, data from brain lesion patients with selective impairment on only one of these tasks provide evidence of neural and cognitive dissociations. We sought to clarify the relationship between AP and AR, and their critical neural substrates, by directly comparing performance of 131 chronic left-hemisphere stroke patients on both tasks--to our knowledge, the largest lesion-based experimental investigation of action cognition to date. Using voxel-based lesion-symptom mapping, we found that lesions to primary motor and somatosensory cortices and inferior parietal lobule were associated with disproportionately impaired performance on AP, whereas lesions to lateral temporo-occipital cortex were associated with a relatively rare pattern of disproportionately impaired performance on AR. In contrast, damage to posterior middle temporal gyrus was associated with impairment on both AP and AR. The distinction between lateral temporo-occipital cortex, critical for recognition, and posterior middle temporal gyrus, important for both tasks, suggests a rough gradient from modality-specific to abstract representations in posterior temporal cortex, the first lesion-based evidence for this phenomenon. Overall, the results of this large patient study help to bring closure to a long standing debate by showing that tool-related AP and AR critically depend on both common and distinct left hemisphere neural substrates, most of which are external to putative human mirror regions. PMID- 26351990 TI - Early Psychosocial Neglect Adversely Impacts Developmental Trajectories of Brain Oscillations and Their Interactions. AB - Rhythmicity is a fundamental property of neural activity at multiple spatiotemporal scales, and associated oscillations represent a critical mechanism for communication and transmission of information across brain regions. During development, these oscillations evolve dynamically as a function of neural maturation and may be modulated by early experiences, positive and/or negative. This study investigated the impact of psychosocial deprivation associated with institutional rearing in early life and the effects of subsequent foster care intervention on developmental trajectories of neural oscillations and their cross frequency correlations. Longitudinally acquired nontask EEGs from three cohorts of children from the Bucharest Early Intervention Project were analyzed. These included abandoned children initially reared in institutions and subsequently randomized to be placed in foster care or receive care as usual (prolonged institutional rearing) and a group of never-institutionalized children. Oscillation trajectories were estimated from 42 to 96 months, that is, 1-3 years after all children in the intervention arm of the study had been placed in foster care. Significant differences between groups were estimated for the amplitude trajectories of cognitive-related gamma, beta, alpha, and theta oscillations. Similar differences were identified as a function of time spent in institutions, suggesting that increased time spent in psychosocial neglect may have profound and widespread effects on brain activity. Significant group differences in cross frequency coupling were estimated longitudinally between gamma and lower frequencies as well as alpha and lower frequencies. Lower cross-gamma coupling was estimated at 96 months in the group of children that remained in institutions at that age compared to the other two groups, suggesting potentially impaired communication between local and long-distance brain networks in these children. In contrast, higher cross-alpha coupling was estimated in this group compared to the other two groups at 96 months, suggesting impaired suppression of alpha-theta and alpha-delta activity, which has been associated with neuropsychiatric disorders. Age at foster care placement had a significant positive modulatory effect on alpha and beta trajectories and their mutual coupling, although by 96 months these trajectories remained distinct from those of never-institutionalized children. Overall, these findings suggest that early psychosocial neglect may profoundly impact neural maturation, particularly the evolution of neural oscillations and their interactions across a broad frequency range. These differences may result in widespread deficits across multiple cognitive domains. PMID- 26351991 TI - Preference for Audiovisual Speech Congruency in Superior Temporal Cortex. AB - Auditory speech perception can be altered by concurrent visual information. The superior temporal cortex is an important combining site for this integration process. This area was previously found to be sensitive to audiovisual congruency. However, the direction of this congruency effect (i.e., stronger or weaker activity for congruent compared to incongruent stimulation) has been more equivocal. Here, we used fMRI to look at the neural responses of human participants during the McGurk illusion--in which auditory /aba/ and visual /aga/ inputs are fused to perceived /ada/--in a large homogenous sample of participants who consistently experienced this illusion. This enabled us to compare the neuronal responses during congruent audiovisual stimulation with incongruent audiovisual stimulation leading to the McGurk illusion while avoiding the possible confounding factor of sensory surprise that can occur when McGurk stimuli are only occasionally perceived. We found larger activity for congruent audiovisual stimuli than for incongruent (McGurk) stimuli in bilateral superior temporal cortex, extending into the primary auditory cortex. This finding suggests that superior temporal cortex prefers when auditory and visual input support the same representation. PMID- 26351992 TI - Communicative Signals Promote Object Recognition Memory and Modulate the Right Posterior STS. AB - Detection of communicative signals is thought to facilitate knowledge acquisition early in life, but less is known about the role these signals play in adult learning or about the brain systems supporting sensitivity to communicative intent. The current study examined how ostensive gaze cues and communicative actions affect adult recognition memory and modulate neural activity as measured by fMRI. For both the behavioral and fMRI experiments, participants viewed a series of videos of an actress acting on one of two objects in front of her. Communicative context in the videos was manipulated in a 2 * 2 design in which the actress either had direct gaze (Gaze) or wore a visor (NoGaze) and either pointed at (Point) or reached for (Reach) one of the objects (target) in front of her. Participants then completed a recognition memory task with old (target and nontarget) objects and novel objects. Recognition memory for target objects in the Gaze conditions was greater than NoGaze, but no effects of gesture type were seen. Similarly, the fMRI video-viewing task revealed a significant effect of Gaze within right posterior STS (pSTS), but no significant effects of Gesture. Furthermore, pSTS sensitivity to Gaze conditions was related to greater memory for objects viewed in Gaze, as compared with NoGaze, conditions. Taken together, these results demonstrate that the ostensive, communicative signal of direct gaze preceding an object-directed action enhances recognition memory for attended items and modulates the pSTS response to object-directed actions. Thus, establishment of a communicative context through ostensive signals remains an important component of learning and memory into adulthood, and the pSTS may play a role in facilitating this type of social learning. PMID- 26351993 TI - Monitoring Different Phonological Parameters of Sign Language Engages the Same Cortical Language Network but Distinctive Perceptual Ones. AB - The study of signed languages allows the dissociation of sensorimotor and cognitive neural components of the language signal. Here we investigated the neurocognitive processes underlying the monitoring of two phonological parameters of sign languages: handshape and location. Our goal was to determine if brain regions processing sensorimotor characteristics of different phonological parameters of sign languages were also involved in phonological processing, with their activity being modulated by the linguistic content of manual actions. We conducted an fMRI experiment using manual actions varying in phonological structure and semantics: (1) signs of a familiar sign language (British Sign Language), (2) signs of an unfamiliar sign language (Swedish Sign Language), and (3) invented nonsigns that violate the phonological rules of British Sign Language and Swedish Sign Language or consist of nonoccurring combinations of phonological parameters. Three groups of participants were tested: deaf native signers, deaf nonsigners, and hearing nonsigners. Results show that the linguistic processing of different phonological parameters of sign language is independent of the sensorimotor characteristics of the language signal. Handshape and location were processed by different perceptual and task-related brain networks but recruited the same language areas. The semantic content of the stimuli did not influence this process, but phonological structure did, with nonsigns being associated with longer RTs and stronger activations in an action observation network in all participants and in the supramarginal gyrus exclusively in deaf signers. These results suggest higher processing demands for stimuli that contravene the phonological rules of a signed language, independently of previous knowledge of signed languages. We suggest that the phonological characteristics of a language may arise as a consequence of more efficient neural processing for its perception and production. PMID- 26351994 TI - Syntax in Action Has Priority over Movement Selection in Piano Playing: An ERP Study. AB - Complex human behavior is hierarchically organized. Whether or not syntax plays a role in this organization is currently under debate. The present ERP study uses piano performance to isolate syntactic operations in action planning and to demonstrate their priority over nonsyntactic levels of movement selection. Expert pianists were asked to execute chord progressions on a mute keyboard by copying the posture of a performing model hand shown in sequences of photos. We manipulated the final chord of each sequence in terms of Syntax (congruent/incongruent keys) and Manner (conventional/unconventional fingering), as well as the strength of its predictability by varying the length of the Context (five-chord/two-chord progressions). The production of syntactically incongruent compared to congruent chords showed a response delay that was larger in the long compared to the short context. This behavioral effect was accompanied by a centroparietal negativity in the long but not in the short context, suggesting that a syntax-based motor plan was prepared ahead. Conversely, the execution of the unconventional manner was not delayed as a function of Context and elicited an opposite electrophysiological pattern (a posterior positivity). The current data support the hypothesis that motor plans operate at the level of musical syntax and are incrementally translated to lower levels of movement selection. PMID- 26351995 TI - Retrieval Goal Modulates Memory for Context. AB - fMRI was employed to assess whether the contents of recollection vary according to retrieval goal. At study, visually presented words were superimposed on urban or rural scenes or a gray background. The word-background pairs were presented in one of three spatial locations. During a scanned test phase, studied and unstudied words were presented. Two different source memory tasks were randomly interleaved. In the "background" task, the requirement was to judge whether the word had been presented against one of the two classes of scene, as opposed to the alternate class or the gray background. In the "location" task, discrimination was between words presented in one of the two lateral locations and words presented in either of the alternate locations. In both tasks, unstudied words required a separate response. In the background task, words studied against scenes elicited greater activity in parahippocampal and retrosplenial cortex than did words studied against the gray background, consistent with prior reports of scene reinstatement effects. Reinstatement effects were also evident in the location task. Relative to the background task, however, the effects were attenuated in parahippocampal cortex. In other regions, including medial prefrontal and posterior cingulate cortex, activity elicited in the location task by items associated with scenes was lower than that elicited by items presented on the gray background. The findings are interpreted as evidence that contextual retrieval is partially modulated by retrieval goal. PMID- 26351996 TI - Four states of mind of the evidence-based practitioner - On the receiving end of the first FRISBEE supplement. PMID- 26351997 TI - Opening the doors of memory: is declarative memory a natural kind? AB - Klein's target article argues that autonoetic consciousness is a necessary condition for memory; this unusually narrow view of the scope of memory implies that only episodic memory is, strictly speaking, memory. The narrow view is opposed to the standard broad view, on which causal connection with past experience is sufficient for memory; on the broad view, both declarative (i.e., episodic and semantic) and procedural memory count as genuine forms of memory. Klein mounts a convincing attack on the broad view, arguing that it opens the 'doors of memory' too far, but this commentary contends that the narrow view does not open them far enough. It may be preferable to adopt an intermediate view of the scope of memory, on which causal connection is sufficient for memory only when it involves encoding, storage, and retrieval of content. More demanding than the simple causal condition but less demanding than the autonoesis condition, the encoding-storage-retrieval condition implies that both episodic and semantic memory count as genuine forms of memory but that procedural memory does not. PMID- 26351998 TI - Incomplete penetrance in the Spanish family with limb-girdle muscular dystrophy type 1F. PMID- 26352001 TI - Role of adenoviruses in obesity. AB - Five human adenovirus subtypes, Ad5, Ad9, Ad31, Ad36, and Ad37, and a non-human adenovirus, SMAM1, are linked to increased adiposity in vitro or in vivo. Experimental infection with Ad5, Ad36, and Ad37 produced excess adiposity or weight gain in animals. Ad9 and Ad31 increase fat storage in tissue culture but are not associated with animal or human obesity. Ad36 is the most extensively studied adipogenic adenovirus and is correlated with some measure of overweight/obesity in humans from multiple countries. The correlation is strongest and most consistent in children, but some studies have been negative in both children and adults. About 30% of overweight/obese children and adults and about 15-20% of lean individuals have Ad36 antibodies in epidemiologic studies. The mechanisms of action of Ad36 are due to the early gene 4, open reading frame 1 (E4-ORF1). Blocking E4-ORF1 with siRNA prevents the effects of Ad36, and transfection of lentivirus with E4-ORF1 reproduces the Ad36 effects. Increased adiposity is caused by stimulation of at least three pathways by Ad36. Cell membrane glucose receptors are increased via the Ras pathway, leading to increased intracellular glucose. Fatty acid synthase is increased, which converts the glucose to fatty acids. Finally, peroxisome proliferator-activated receptor gamma is increased, resulting in differentiation of adult stem cells into adipocytes. CONCLUSIONS: several adenoviruses increase adiposity in animals and are associated with obesity in humans. There are critical gaps in the literature needing further investigation including evaluation of other adenovirus subtypes and better research designs to improve the strength of causal inferences. PMID- 26352002 TI - Spironolactone inhibits podocyte motility via decreasing integrin beta1 and increasing integrin beta3 in podocytes under high-glucose conditions. AB - Integrin beta1 and beta3 expression by podocytes is required to maintain glomerular structural integrity. Previous studies have shown that aldosterone (ALD) is involved in glomerular podocyte injury, and mineralocorticoid receptor (MR) blocker spironolactone effectively reduces proteinuria in patients with diabetic nephropathy. The present study was designed to observe the effects of spironolactone on beta1 and beta3 integrin expression and podocyte motility under in vitro diabetic conditions. Immortalized mouse podocytes were cultured in media containing normal glucose (NG) levels, high glucose (HG) or HG plus spironolacton. The expression of beta1 and beta3 integrin in podocytes was detected by reverse transcription quantitative polymerase chain reaction, immunofluorescence and western blot analyses. The effects of spironolacton on podocyte motility was further evaluated using a wound healing assay. HG stimulation markedly decreased mRNA and protein expression of integrin beta1, and significantly increased mRNA and protein expression of integrin beta3 in cultured podocytes. However, simultaneous treatment with spironolacton (10-7 mol/l) significantly attenuated HG-mediated increases in integrin beta3 and decreases in integrin beta1 expression. Furthermore, the migration of podocytes induced by HG was abrogated by concomitant treatment with spironolacton. In conclusion, the present study suggested that HG decreased the expression of integrin beta1 in cultured podocytes, accompanied with an increase of integrin beta3. Spironolactone inhibited cell motility and stabilized podoctyes treated with HG, probably through partly normalizing the expression of integrin beta1 and decreasing the expression of integrin beta3. PMID- 26352003 TI - Dioscin Derived from Solanum melongena L. "Usukawamarunasu" Attenuates alpha-MSH Induced Melanogenesis in B16 Murine Melanoma Cells via Downregulation of Phospho CREB and MITF. AB - This study aimed to chemically isolate and explore an antimelanogenesis inducer in extracts of Solanum melongena L. "Usukawamarunasu" eggplant. We successfully identified dioscin ([25R]-Spirost-5-en-3beta-yl) 2-O-(6-deoxy-alpha-L mannopyranosyl) - 4-O-(6-deoxy-alpha-L-mannopyranosyl)-beta-D-glucopyranoside] in the plant, and examined the effects of alpha-melanocyte-stimulating hormone (MSH) induced melanogenesis in B16 murine melanoma cells by this plant-derived dioscin. Immunoblot analysis suggested that dioscin reduced the expression of tyrosinase, tyrosinase-related protein-1 (TRP-1), and TRP-2, resulting in inhibition of intracellular production of melanin. In addition, dioscin caused reduction of phosphorylated cAMP-responsive element binding protein 1 transcription factors (CREB), which led to a reduction of microphthalmia-related transcription factor (MITF) in alpha-MSH-stimulated cells, but did not affect phosphorylation of extracellular signal-regulated kinase. Furthermore, dioscin significantly downregulated the expression of tyrosinase, TRP-1, and TRP-2, which led to the reduction of alpha-MSH-induced melanogenesis in B16 cells. These results suggest that dioscin may decrease the level of MITF via inhibition of phosphorylation of CREB in alpha-MSH-induced melanogenesis in B16 cells. PMID- 26352004 TI - GdCl3 suppresses the malignant potential of hepatocellular carcinoma by inhibiting the expression of CD206 in tumor-associated macrophages. AB - In the present study, we aimed to ascertain whether there is a correlation between CD206 expression in tumor associated-macrophages (TAMs) and the prognosis of primary hepatocellular carcinomas (HCC) and we investigated the effect of GdCl3 on HCC. The expression of CD206 in HCC tumor tissues and peri-carcinoma tissues was measured using an array for liver tissues. The effects of GdCl3 on CD206 expression were examined in stimulated RAW264.7 cells. Target gene expression was evaluated by RT-PCR, western blotting and immunohistochemistry. The transwell system was used to assess the invasiveness of HCC cells. Finally, we established a mouse model for HCC using N-nitrosodiethylamine (DEN) to determine the effect of GdCl3 on HCC. Liver tissue array analysis revealed that CD206 was highly expressed in the HCC tissues compared to the level in peri carcinoma tissue. We found that GdCl3 suppressed the expression of CD206 in the M2 macrophage phenotype of stimulated RAW264.7 cells with an IC10 value of 0.07 ug/ul. In addition, GdCl3 also induced cell apoptosis in the RAW264.7 cells. Addition of GdCl3 into the culture medium of RAW264.7 cells markedly reduced the invasive ability of Hepa1-6 cells compared to the control cells. Accordingly, GdCl3 treatment increased the expression of the epithelial-mesenchymal transition (EMT)-related protein E-cadherin while expression of N-cadherin, TWIST and Snail was reduced in IL-4-stimulated cells. Moreover, GdCl3 treatment inhibited HCC progression in DEN-induced HCC mice, possibly by downregulating CD206. Our findings indicate that CD206 is a potential biomarker for predicting HCC prognosis and that GdCl3 suppresses HCC progression by downregulating the expression of CD206 in TAMs. PMID- 26352005 TI - Reply to Bush and Hillier. PMID- 26352006 TI - Pharmacotherapeutic management of erectile dysfunction. AB - Erectile dysfunction is a common condition in aging men and significantly affects their quality of life and interpersonal relationships. Its prevalence and incidence are associated with aging, lifestyle factors and cardiovascular comorbidities. Preoccupation with male virility has been present for centuries, and a wide variety of herbs and potions have been used to treat any sexual deficiencies. Recent major advances in understanding of erectile physiology and pathophysiology led to development of currently available systemic and local pharmacotherapies. They are designed to work either centrally or peripherally and to either suppress anti-erectile mechanisms, enhance the pro-erectile ones or influence both. Since all the current formulations have variable safety and efficacy profiles, the search for highly specific, simple, convenient and clinically effective impotence treatments or prophylactics continues. PMID- 26352008 TI - Virtual reality training for improving the skills needed for performing surgery of the ear, nose or throat. AB - BACKGROUND: Virtual reality simulation uses computer-generated imagery to present a simulated training environment for learners. This review seeks to examine whether there is evidence to support the introduction of virtual reality surgical simulation into ear, nose and throat surgical training programmes. OBJECTIVES: 1. To assess whether surgeons undertaking virtual reality simulation-based training achieve surgical ('patient') outcomes that are at least as good as, or better than, those achieved through conventional training methods.2. To assess whether there is evidence from either the operating theatre, or from controlled (simulation centre-based) environments, that virtual reality-based surgical training leads to surgical skills that are comparable to, or better than, those achieved through conventional training. SEARCH METHODS: The Cochrane Ear, Nose and Throat Disorders Group (CENTDG) Trials Search Co-ordinator searched the CENTDG Trials Register; Central Register of Controlled Trials (CENTRAL 2015, Issue 6); PubMed; EMBASE; ERIC; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 27 July 2015. SELECTION CRITERIA: We included all randomised controlled trials and controlled trials comparing virtual reality training and any other method of training in ear, nose or throat surgery. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by The Cochrane Collaboration. We evaluated both technical and non-technical aspects of skill competency. MAIN RESULTS: We included nine studies involving 210 participants. Out of these, four studies (involving 61 residents) assessed technical skills in the operating theatre (primary outcomes). Five studies (comprising 149 residents and medical students) assessed technical skills in controlled environments (secondary outcomes). The majority of the trials were at high risk of bias. We assessed the GRADE quality of evidence for most outcomes across studies as 'low'. Operating theatre environment (primary outcomes) In the operating theatre, there were no studies that examined two of three primary outcomes: real world patient outcomes and acquisition of non-technical skills. The third primary outcome (technical skills in the operating theatre) was evaluated in two studies comparing virtual reality endoscopic sinus surgery training with conventional training. In one study, psychomotor skill (which relates to operative technique or the physical co-ordination associated with instrument handling) was assessed on a 10-point scale. A second study evaluated the procedural outcome of time-on task. The virtual reality group performance was significantly better, with a better psychomotor score (mean difference (MD) 1.66, 95% CI 0.52 to 2.81; 10 point scale) and a shorter time taken to complete the operation (MD -5.50 minutes, 95% CI -9.97 to -1.03). Controlled training environments (secondary outcomes) In a controlled environment five studies evaluated the technical skills of surgical trainees (one study) and medical students (three studies). One study was excluded from the analysis. Surgical trainees: One study (80 participants) evaluated the technical performance of surgical trainees during temporal bone surgery, where the outcome was the quality of the final dissection. There was no difference in the end-product scores between virtual reality and cadaveric temporal bone training. Medical students: Two other studies (40 participants) evaluated technical skills achieved by medical students in the temporal bone laboratory. Learners' knowledge of the flow of the operative procedure (procedural score) was better after virtual reality than conventional training (SMD 1.11, 95% CI 0.44 to 1.79). There was also a significant difference in end product score between the virtual reality and conventional training groups (SMD 2.60, 95% CI 1.71 to 3.49). One study (17 participants) revealed that medical students acquired anatomical knowledge (on a scale of 0 to 10) better during virtual reality than during conventional training (MD 4.3, 95% CI 2.05 to 6.55). No studies in a controlled training environment assessed non-technical skills. AUTHORS' CONCLUSIONS: There is limited evidence to support the inclusion of virtual reality surgical simulation into surgical training programmes, on the basis that it can allow trainees to develop technical skills that are at least as good as those achieved through conventional training. Further investigations are required to determine whether virtual reality training is associated with better real world outcomes for patients and the development of non-technical skills. Virtual reality simulation may be considered as an additional learning tool for medical students. PMID- 26352007 TI - Intravitreal steroids versus observation for macular edema secondary to central retinal vein occlusion. AB - BACKGROUND: Central retinal vein occlusion (CRVO) is a common retinal vascular abnormality associated with conditions such as hypertension, diabetes, glaucoma, and a wide variety of hematologic disorders. Macular edema (ME) represents an important vision-threatening complication of CRVO. Intravitreal steroids (IVS), such as triamcinolone acetonide, have been utilized to treat macular edema stemming from a variety of etiologies and may be a treatment option for CRVO-ME. OBJECTIVES: To explore the effectiveness and safety of intravitreal steroids in the treatment of CRVO-ME. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2014 Issue 10), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to November 2014), EMBASE (January 1980 to November 2014), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 13 November 2014. For all included primary studies, we used The Science Citation Index (3 December 2014) and manually reviewed reference lists to identify other possible relevant trials. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that compared intravitreal steroids, of any dosage and duration of treatment of at least six months, with observation for the treatment of CRVO-ME. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts identified from the electronic searches and assessed full-text articles from potentially eligible trials. Two review authors independently assessed trial characteristics, risk of bias, and extracted data from included trials. We contacted investigators of included trials for desired data not provided in the trial reports. MAIN RESULTS: We included two RCTs that enrolled a total of 708 participants with CRVO-ME. SCORE compared triamcinolone acetonide intravitreal injections (n = 165) with observation (n = 72); GENEVA compared dexamethasone intravitreal implants (n = 290) with sham injections (n = 147). We observed characteristics indicative of high risk of bias due to incomplete outcome data in SCORE and selective outcome reporting in GENEVA. Loss to follow-up was high with 10% in the steroid groups and almost twice as much (17%) in the observation group. GENEVA enrolled participants with both branch and central retinal vein occlusion, but did not present subgroup data for the CRVO-ME population. A qualitative assessment of the results from GENEVA indicated that the dexamethasone implant was not associated with improvement in visual acuity after six months among participants with CRVO ME. Although the SCORE investigators reported that participants treated with 1 mg (n = 82) or 4 mg (n = 83) triamcinolone intravitreal injections were five times more likely to have gained 15 letters or more in visual acuity compared with participants in the observation group (1 mg; risk ratio (RR): 5.27; 95% confidence interval (CI) 1.62 to 17.15; 4 mg RR 4.92; 95% CI 1.50 to 16.10) by the eighth-month follow-up examination, the average visual acuity decreased in all three groups. However, eyes treated with triamcinolone lost fewer letters than participants in the observation group at 8 months (1 mg mean difference (MD): 8.70 letters, 95% CI 1.86 to 15.54; 4 mg MD: 9.80 letters, 95% CI 3.32 to 16.28). A higher incidence of adverse events was noted with IVS therapy when compared with observation alone. As many as 20% to 35% of participants experienced an adverse event in the IVS groups compared with 8% of participants in the observation group of the SCORE study. The GENEVA investigators reported 63% in the treatment arm versus 43% in the observation arm experienced an adverse event. The most commonly encountered adverse events were elevated intraocular pressure, progression of cataracts, and retinal neovascularization. We graded the quality of evidence as low due to study limitations, imprecision of treatment estimates, and selective outcome reporting. AUTHORS' CONCLUSIONS: The two RCTs reviewed herein provide insufficient evidence to determine the benefits of IVS for individuals with CRVO-ME. The improvement in visual acuity noted in the SCORE trial should be interpreted with caution as outcome data were missing for a large proportion of the observation group. Adverse events were observed more often with IVS treatment compared with observation/no treatment. PMID- 26352009 TI - Microvascular complications and prevalence of urgency incontinence in Japanese patients with type 2 diabetes mellitus: The dogo study. AB - AIMS: Diabetes was significantly positively associated with urgency incontinence in several epidemiological studies. We examine the association between diabetic neuropathy, which we defined based on neuropathic symptoms, the absence of the Achilles reflex, and/or abnormal vibration perception, and urgency incontinence among Japanese patients with type 2 diabetes mellitus. METHODS: Study subjects were 742 Japanese patients with type 2 diabetes mellitus, aged 19-70 years, who had undergone blood tests at our institutions. A self-administered questionnaire was used to collect information on the variables under study. Urgency incontinence was defined as present when a subject answered "once a week or more" to the question: "Within one week, how often do you leak urine because you cannot defer the sudden desire to urinate ?". Diabetic neuropathy was diagnosed if the patients showed two or more of the following three characteristics: neuropathic symptoms, the absence of the Achilles reflex, and/or abnormal vibration perception. Adjustment was made for sex, age, body mass index, duration of type 2 diabetes mellitus, current smoking, hypertension, dyslipidemia, glycated hemoglobin, stroke, coronary artery disease, insulin therapy, diabetic retinopathy, diabetic nephropathy, and diabetic neuropathy. RESULTS: The prevalence of urgency incontinence was 8.6%. Diabetic neuropathy was independently positively associated with urgency incontinence: the adjusted OR was 2.20 (95%CI: 1.16-4.36). Associations between diabetic retinopathy or nephropathy and the prevalence of urgency incontinence were not significant. CONCLUSIONS: In Japanese patients with type 2 diabetes mellitus, only diabetic neuropathy was independently positively associated with urgency incontinence. Neurourol. Urodynam. 35:1024-1027, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26352010 TI - Leishmania mexicana amastigotes inhibit p38 and JNK and activate PI3K/AKT: role in the inhibition of apoptosis of dendritic cells. AB - Leishmania mexicana is the causal agent of cutaneous leishmaniasis in Mexico. Dendritic cells (DC) are one of the host cells of Leishmania parasites. Intracellular microorganisms inhibit host cell apoptosis as a strategy to ensure their survival in infected cells. We have previously shown that Leishmania mexicana promastigotes and amastigotes inhibit camptothecin-induced apoptosis of monocyte-derived dendritic cells (moDC), but the mechanisms underlying the inhibition of apoptosis of DC by Leishmania have not been established. MAP kinases and PI3K participate in the process of apoptosis and are modulated by different species of Leishmania. As shown in this study, the infection of moDC with L. mexicana amastigotes diminished significantly the phosphorylation of the MAP kinases p38 and JNK. The inhibition of both kinases diminished significantly DNA fragmentation in moDC stimulated with camptothecin. On the other hand, L. mexicana amastigotes were able to activate the anti-apoptotic pathways PI3K and AKT. Our results indicate that L. mexicana amastigotes have the capacity to diminish MAP kinases activation and activate PI3K and AKT, which is probably one of the strategies employed by L. mexicana amastigotes to inhibit apoptosis in the infected moDC. PMID- 26352011 TI - Manumycin A from a new Streptomyces strain induces endoplasmic reticulum stress mediated cell death through specificity protein 1 signaling in human oral squamous cell carcinoma. AB - Manumycin A (Manu A) is a natural antibiotic produced by new Streptomyces strain, exhibiting antitumor and anticancer effects. However, the anticancer effects of Manu A on oral squamous cell carcinoma (OSCC) have not been reported. OSCC is an aggressive type of cancer because of its poor prognosis and low survival rate despite advanced medical treatment. We observed that Manu A reduced cell growth and Sp1 protein levels in OSCC cell lines (HN22 and HSC4) in a dose- and time dependent manner. We also observed downregulation of Sp1 downstream target genes such as p27, p21, Mcl-1 and survivin. Moreover, nuclear staining with DAPI showed that Manu A was able to cause nuclear condensation and further fragmentation. Flow cytometry analyses using Annexin V and propiodium iodide supported Manu A mediated apoptotic cell death of OSCC cells. Furthermore, Bcl-2 family such as mitochondrial pro-apoptotic Bax, anti-apoptotic Bcl-xl and Bid were regulated by Manu A, triggering the mitochondrial apoptotic pathway. In conclusion, these results indicate that Manu A is a potential to treat human OSCC via cell apoptosis through the downregulation of Sp1. PMID- 26352012 TI - A GPU OpenCL based cross-platform Monte Carlo dose calculation engine (goMC). AB - Monte Carlo (MC) simulation has been recognized as the most accurate dose calculation method for radiotherapy. However, the extremely long computation time impedes its clinical application. Recently, a lot of effort has been made to realize fast MC dose calculation on graphic processing units (GPUs). However, most of the GPU-based MC dose engines have been developed under NVidia's CUDA environment. This limits the code portability to other platforms, hindering the introduction of GPU-based MC simulations to clinical practice. The objective of this paper is to develop a GPU OpenCL based cross-platform MC dose engine named goMC with coupled photon-electron simulation for external photon and electron radiotherapy in the MeV energy range. Compared to our previously developed GPU based MC code named gDPM (Jia et al 2012 Phys. Med. Biol. 57 7783-97), goMC has two major differences. First, it was developed under the OpenCL environment for high code portability and hence could be run not only on different GPU cards but also on CPU platforms. Second, we adopted the electron transport model used in EGSnrc MC package and PENELOPE's random hinge method in our new dose engine, instead of the dose planning method employed in gDPM. Dose distributions were calculated for a 15 MeV electron beam and a 6 MV photon beam in a homogenous water phantom, a water-bone-lung-water slab phantom and a half-slab phantom. Satisfactory agreement between the two MC dose engines goMC and gDPM was observed in all cases. The average dose differences in the regions that received a dose higher than 10% of the maximum dose were 0.48-0.53% for the electron beam cases and 0.15-0.17% for the photon beam cases. In terms of efficiency, goMC was ~4-16% slower than gDPM when running on the same NVidia TITAN card for all the cases we tested, due to both the different electron transport models and the different development environments. The code portability of our new dose engine goMC was validated by successfully running it on a variety of different computing devices including an NVidia GPU card, two AMD GPU cards and an Intel CPU processor. Computational efficiency among these platforms was compared. PMID- 26352013 TI - Sp1 cooperates with Sp3 to upregulate MALAT1 expression in human hepatocellular carcinoma. AB - Long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), also known as nuclear-enriched transcript 2 (NEAT2), is highly conserved among mammals and highly expressed in the nucleus. It was first identified in lung cancer as a prognostic marker for metastasis but is also associated with several other solid tumors. In hepatocellular carcinoma (HCC), MALAT1 is a novel biomarker for predicting tumor recurrence after liver transplantation. The mechanism of overexpression in tumor progression remains unclear. In the present study, we investigated the role of specificity protein 1/3 (Sp1/3) in regulation of MALAT1 transcription in HCC cells. The results showed a high expression of Sp1, Sp3 and MALAT1 in HCC vs. paired non-tumor liver tissues, which was associated with the AFP level (Sp1, r=7.44, P=0.0064; MALAT1, r=12.37, P=0.0004). Co-silencing of Sp1 and Sp3 synergistically repressed MALAT1 expression. Sp1 binding inhibitor, mithramycin A (MIT), also inhibited MALAT1 expression in HCC cells. In conclusion, the upstream of MALAT1 contains five Sp1/3 binding sites, which may be responsible for MALAT1 transcription. Inhibitors, such as MIT, provide a potential therapeutic strategy for HCC patients with MALAT1 overexpression. PMID- 26352014 TI - Polo-like kinase 3 inhibits osteosarcoma cell proliferation and tumorigenesis via cooperative interaction with p21. AB - Polo-like kinase 3 (Plk3) is a member of the Plk family. It is dysregulated in certain types of cancer, including colorectal and pancreatic cancer. However, the expression status and biological function of Plk3 in osteosarcoma (OS) remain poorly understood. Following evaluation of the role of Plk3 in OS, the present study indicates that Plk3 is downregulated in OS cell lines and tissues, and increased expression levels of Plk3 are associated with improved rates of overall survival of patients. In addition, to investigate the role of Plk3 in cell proliferation and tumorigenicity in vitro, two recombinant lentiviruses expressing Plk3 short hairpin RNA, as well as a recombinant plasmid carrying Plk3, were developed and transfected into Saos-2 and U2OS cells, respectively. Cell cycle analysis by flow cytometry demonstrated the influence of Plk3 on the arrest of cell cycle progression at the G1 phase. Following knock down of Plk3, the growth and colony formation of Saos-2 cells increased significantly, whereas the overexpression of Plk3 resulted in the opposite trend. Furthermore, a 5 ethynyl-2'-deoxyuridine assay, using U2OS cell lines, indicated the same tendency. The in vivo interaction between Plk3 and p21 in Saos-2 cells was detected and the protein level of p21 was observed to be consistent with that of Plk3. These results imply that Plk3 is involved in the inhibition of cell proliferation and tumorigenesis, which may occur via interactions with p21, thus, Plk3 may be considered as a potential candidate for targeted therapy of OS. PMID- 26352016 TI - Corrigendum: pseudohalide-induced moisture-tolerance in perovskite CH3 NH3 Pb(SCN)2 I thin films. PMID- 26352018 TI - Synthesis, single-crystal structure and characterization of (CH3 NH3 )2 Pb(SCN)2 I2. AB - The perovskite phase (CH3 NH3 )2 Pb(SCN)2 I2 with a structure closely related to the K2 NiF4 -type was identified as the product of the reaction of CH3 NH3 I and Pb(SCN)2 by single-crystal X-ray analysis. This extends the range of suitable dyes for solar cell applications to a class of perovskite-related structures of the general composition (AMX3 )n (AX)m . PMID- 26352019 TI - Designing host materials for sulfur cathodes: from physical confinement to surface chemistry. AB - Sulfiphilic surfaces: The design of novel host materials for sulfur cathodes in lithium-sulfur batteries has been achieved through modification of the surface chemistry, by employing sulfiphilic surfaces with high electrical conductivity to develop stable, high-energy batteries. Compared to the physical-confinement technique, systems prepared by this method exhibited remarkable enhancements of both capacity and cycling stability. PMID- 26352020 TI - Polymeric micelle assembly for the smart synthesis of mesoporous platinum nanospheres with tunable pore sizes. AB - A facile method for the fabrication of well-dispersed mesoporous Pt nanospheres involves the use of a polymeric micelle assembly. A core-shell-corona type triblock copolymer [poly(styrene-b-2-vinylpyridine-b-ethylene oxide), PS-b-P2VP-b PEO] is employed as the pore-directing agent. Negatively charged PtCl4 (2-) ions preferably interact with the protonated P2VP(+) blocks while the free PEO chains prevent the aggregation of the Pt nanospheres. The size of the mesopores can be finely tuned by varying the length of the PS chain. Furthermore, it is demonstrated that the metallic mesoporous nanospheres thus obtained are promising candidates for applications in electrochemistry. PMID- 26352021 TI - An inexpensive and recyclable silver-foil catalyst for the cyclopropanation of alkenes with diazoacetates under mechanochemical conditions. AB - The diastereoselective cyclopropanation of various alkenes with diazoacetate derivatives can be achieved under mechanochemical conditions using metallic silver foil and a stainless-steel vial and ball system. This solvent-free method displays analogous reactivity and selectivity to solution-phase reactions without the need for slow diazoacetate addition or an inert atmosphere. The heterogeneous silver-foil catalyst system is easily recyclable without any appreciable loss of activity or selectivity being observed. The cyclopropanation products were obtained with excellent diastereoselectivities (up to 98:2 d.r.) and in high yields (up to 96 %). PMID- 26352022 TI - A reduced 2Fe2S cluster probe of sulfur-hydrogen versus sulfur-gold interactions. AB - The Ph3 PAu(+) cation, renowned as an isolobal analogue of H(+) , was found to serve as a proton surrogate and form a stable Au2 Fe2 complex, [(MU-SAuPPh3 )2 {Fe(CO)3 }2 ], analogous to the highly reactive dihydrosulfide [(MU-SH)2 {Fe(CO)3 }2 ]. Solid-state X-ray diffraction analysis found the two SAuPPh3 and SH bridges in anti configurations. VT NMR studies, supported by DFT computations, confirmed substantial barriers of approximately 25 kcal mol(-1) to intramolecular interconversion between the three stereoisomers of [(MU-SH)2 {Fe(CO)3 }2 ]. In contrast, the largely dative S?Au bond in MU-SAuPPh3 facilitates inversion at S and accounts for the facile equilibration of the SAuPPh3 units, with an energy barrier half that of the SH analogue. The reactivity of the gold-protected sulfur atoms of [(MU-SAuPPh3 )2 {Fe(CO)3 }2 ] was accessed by release of the gold ligand with a strong acid to generate the [(MU-SH)2 {Fe(CO)3 }2 ] precursor of the [FeFe]H2 ase-active-site biomimetic [(MU2 -SCH2 (NR)CH2 S){Fe(CO)3 }2 ]. PMID- 26352023 TI - Self-assembly of alpha-helical polypeptides driven by complex coacervation. AB - Reported is the ability of alpha-helical polypeptides to self-assemble with oppositely-charged polypeptides to form liquid complexes while maintaining their alpha-helical secondary structure. Coupling the alpha-helical polypeptide to a neutral, hydrophilic polymer and subsequent complexation enables the formation of nanoscale coacervate-core micelles. While previous reports on polypeptide complexation demonstrated a critical dependence of the nature of the complex (liquid versus solid) on chirality, the alpha-helical structure of the positively charged polypeptide prevents the formation of beta-sheets, which would otherwise drive the assembly into a solid state, thereby, enabling coacervate formation between two chiral components. The higher charge density of the assembly, a result of the folding of the alpha-helical polypeptide, provides enhanced resistance to salts known to inhibit polypeptide complexation. The unique combination of properties of these materials can enhance the known potential of fluid polypeptide complexes for delivery of biologically relevant molecules. PMID- 26352024 TI - Liquid-crystalline mesogens based on cyclo[6]aramides: distinctive phase transitions in response to macrocyclic host-guest interactions. AB - Producing macrocyclic mesogens that are responsive to guest encapsulation presents a significant challenge. Cyclo[6]aramides, a type of macrocycle with a hydrogen-bond-constrained backbone, exhibit thermotropic lamellar, discotic nematic, hexagonal, and rectangular columnar mesophases over a considerably wide temperature range, including at room temperature. Additionally, cyclo[6]aramides show unusual mesophase transitions from lamellar to hexagonal columnar phase mediated by macrocyclic host-guest (H-G) interactions between the macrocycles and alkylammonium salts. The phase transition, triggered by an organic guest engaging in H-G interactions with a macrocyclic cavity, provides a novel strategy for manipulating the properties of liquid-crystalline materials. The crystal structure of a homologous cyclo[6]aramide reveals a disk-shaped, near-planar molecular backbone that facilitates intermolecular pi-pi stacking and leads to columnar assembly. PMID- 26352025 TI - A 2:1 receptor/C60 complex as a nanosized universal joint. AB - Buckycatcher II, a C51 H24 hydrocarbon with two corannulene pincers on a dibenzonorbornadiene tether, exhibits an affinity toward C60 in organic solvents that is dramatically higher than the original buckycatcher C60 H28 and other corannulene-based molecular receptors for fullerenes. In addition to the formation of an usual 1:1 C60 @catcher inclusion complex, a trimeric C60 @(catcher)2 assembly is detected in solutions and in the solid state. X-ray structure determination reveals a remarkable "universal joint" solvent-free crystal arrangement of the trimer, with a single fullerene cage wrapped by four corannulene subunits of two cooperating catcher receptors. PMID- 26352027 TI - Definitive molecular level characterization of defects in UiO-66 crystals. AB - The identification and characterization of defects, on the molecular level, in metal-organic frameworks (MOFs) remain a challenge. With the extensive use of single-crystal X-ray diffraction (SXRD), the missing linker defects in the zirconium-based MOF UiO-66, Zr6 O4 (OH)4 (C8 H4 O4 )6 , have been identified as water molecules coordinated directly to the zirconium centers. Charge balancing is achieved by hydroxide anions, which are hydrogen bonded within the pores of the framework. Furthermore, the precise nature of the defects and their concentration can be manipulated by altering the starting materials, synthesis conditions, and post-synthetic modifications. PMID- 26352026 TI - The energetics of a three-state protein folding system probed by high-pressure relaxation dispersion NMR spectroscopy. AB - The energetic and volumetric properties of a three-state protein folding system, comprising a metastable triple mutant of the Fyn SH3 domain, have been investigated using pressure-dependent (15) N-relaxation dispersion NMR from 1 to 2500 bar. Changes in partial molar volumes (DeltaV) and isothermal compressibilities (DeltakappaT ) between all the states along the folding pathway have been determined to reasonable accuracy. The partial volume and isothermal compressibility of the folded state are 100 mL mol(-1) and 40 MUL mol(-1) bar( 1) , respectively, higher than those of the unfolded ensemble. Of particular interest are the findings related to the energetic and volumetric properties of the on-pathway folding intermediate. While the latter is energetically close to the unfolded state, its volumetric properties are similar to those of the folded protein. The compressibility of the intermediate is larger than that of the folded state reflecting the less rigid nature of the former relative to the latter. PMID- 26352028 TI - Realizing both high energy and high power densities by twisting three carbon nanotube-based hybrid fibers. AB - Energy storage devices, such as lithium-ion batteries and supercapacitors, are required for the modern electronics. However, the intrinsic characteristics of low power densities in batteries and low energy densities in supercapacitors have limited their applications. How to simultaneously realize high energy and power densities in one device remains a challenge. Herein a fiber-shaped hybrid energy storage device (FESD) formed by twisting three carbon nanotube hybrid fibers demonstrates both high energy and power densities. For the FESD, the energy density (50 mWh cm(-3) or 90 Wh kg(-1) ) many times higher than for other forms of supercapacitors and approximately 3 times that of thin-film batteries; the power density (1 W cm(-3) or 5970 W kg(-1) ) is approximately 140 times of thin film lithium-ion battery. The FESD is flexible, weaveable and wearable, which offers promising advantages in the modern electronics. PMID- 26352029 TI - Detection of the short-lived radical cation intermediate in the electrooxidation of N,N-dimethylaniline by mass spectrometry. AB - The N,N-dimethylaniline (DMA) radical cation DMA(.+) , a long-sought transient intermediate, was detected by mass spectrometry (MS) during the electrochemical oxidation of DMA. This was accomplished by coupling desorption electrospray ionization (DESI) MS with a waterwheel working electrode setup to sample the surface of the working electrode during electrochemical analysis. This study clearly shows that DESI-based electrochemical MS is capable of capturing electrochemically generated intermediates with half-lives on the order of microseconds, which is 4-5 orders of magnitude faster than previously reported electrochemical mass spectrometry techniques. PMID- 26352030 TI - Regioregular synthesis of azaborine oligomers and a polymer with a syn conformation stabilized by N-H???pi interactions. AB - The regioregular synthesis of the first azaborine oligomers and a corresponding conjugated polymer was accomplished by Suzuki-Miyaura coupling methods. An almost perfectly coplanar syn arrangement of the heterocycles was deduced from an X-ray crystal structure of the dimer, which also suggested that N?H???pi interactions play an important role. Computational studies further supported these experimental observations and indicated that the electronic structure of the longer azaborine oligomers and polymer resembles that of poly(cyclohexadiene) more than poly(p-phenylene). A comparison of the absorption and emission properties of the polymer with those of the oligomers revealed dramatic bathochromic shifts upon chain elongation, thus suggesting highly effective extension of conjugation. PMID- 26352031 TI - Chiral polymers of intrinsic microporosity: selective membrane permeation of enantiomers. AB - Following its resolution by diastereomeric complexation, 5,5',6,6'-tetrahydroxy 3,3,3',3'-tetramethyl-1,1'-spirobisindane (TTSBI) was used to synthesize a chiral ladder polymer, (+)-PIM-CN. (+)-PIM-COOH was also synthesized by the acid hydrolysis of (+)-PIM-CN. Following characterization, both (+)-PIM-CN and (+)-PIM COOH were solvent cast directly into semipermeable membranes and evaluated for their ability to enable the selective permeation of a range of racemates, including mandelic acid (Man), Fmoc-phenylalanine, 1,1'-bi-2-naphthol (binol), and TTSBI. High ee values were observed for a number of analytes, and both materials exhibited high permeation rates. A selective diffusion-permeation mechanism was consistent with the results obtained with these materials. Their high permeability, processability, and ease of chemical modification offer considerable potential for liquid-phase membrane separations and related separation applications. PMID- 26352032 TI - Ring expansion of epoxides under Bronsted base catalysis: formal [3+2] cycloaddition of beta,gamma-epoxy esters with imines providing 2,4,5 trisubstituted 1,3-oxazolidines. AB - A novel ring-expansion reaction of epoxides under Bronsted base catalysis was developed. The formal [3+2] cycloaddition reaction of beta,gamma-epoxy esters with imines proceeds in the presence of triazabicyclodecene (TBD) as a superior Bronsted base catalyst to afford 2,4,5-trisubstituted 1,3-oxazolidines in a highly diastereoselective manner. This reaction involves the ring opening of the epoxides with the aid of the Bronsted base catalyst to generate alpha,beta unsaturated esters having an alkoxide at the allylic position, which would formally serve as a synthetic equivalent of the 1,3-dipole, followed by a cycloaddition reaction with imines in a stepwise fashion. This methodology enables the facile synthesis of enantioenriched 1,3-oxazolidines from easily accessible enantioenriched epoxides. PMID- 26352033 TI - Rare-earth-metal nitridophosphates through high-pressure metathesis. AB - Developing a synthetic method to target an broad spectrum of unknown phases can lead to fascinating discoveries. The preparation of the first rare-earth-metal nitridophosphate LiNdP4 N8 is reported. High-pressure solid-state metathesis between LiPN2 and NdF3 was employed to yield a highly crystalline product. The in situ formed LiF is believed to act both as the thermodynamic driving force and as a flux to aiding single-crystal formation in dimensions suitable for crystal structure analysis. Magnetic properties stemming from Nd(3+) ions were measured by SQUID magnetometry. LiNdP4 N8 serves as a model system for the exploration of rare-earth-metal nitridophosphates that may even be expanded to transition metals. High-pressure metathesis enables the systematic study of these uncharted regions of nitride-based materials with unprecedented properties. PMID- 26352034 TI - Conversion of anthranilate synthase into isochorismate synthase: implications for the evolution of chorismate-utilizing enzymes. AB - Chorismate-utilizing enzymes play a vital role in the biosynthesis of metabolites in plants as well as free-living and infectious microorganisms. Among these enzymes are the homologous primary metabolic anthranilate synthase (AS) and secondary metabolic isochorismate synthase (ICS). Both catalyze mechanistically related reactions by using ammonia and water as nucleophiles, respectively. We report that the nucleophile specificity of AS can be extended from ammonia to water by just two amino acid exchanges in a channel leading to the active site. The observed ICS/AS bifunctionality demonstrates that a secondary metabolic enzyme can readily evolve from a primary metabolic enzyme without requiring an initial gene duplication event. In a general sense, these findings add to our understanding how nature has used the structurally predetermined features of enzyme superfamilies to evolve new reactions. PMID- 26352036 TI - The Continuously Learning Health System: Recommendations From the Josiah Macy Jr. Foundation. PMID- 26352037 TI - How to Write an Outcome Statement. AB - Educators within the health professions are increasingly asked to demonstrate outcomes of educational interventions. Within academia and clinical practice, educators are expected to measure, monitor, and, in many cases, report outcomes of their work. As continuing education transitions to a more deliberate emphasis on outcomes, common questions include how to identify and measure outcomes and how to write an outcome statement. This article will focus on how to write an outcome statement. PMID- 26352038 TI - Staff Nurses Eliminated Catheter-Associated Urinary Tract Infections in a Neurosurgical Intensive Care Unit. AB - Catheter-associated urinary tract infections (CAUTIs) are among the leading causes of health care-associated infections in neurosurgical populations. Successful reduction of CAUTIs involve the development of staff nurses as front line change agents equipped with preventative strategies, educational interventions, and sustainable maintenance for positive patient outcomes. PMID- 26352039 TI - International Perspectives in Leadership Development: Part II. AB - In the second part of this two-part series, leadership development perspectives are shared from the opening of the Penn Wharton China Center in Beijing. The symposium brought national leaders from Chinese academic settings and professional organizations together with thought leaders from the United States to discuss nursing leadership across the care continuum. Highlights of demographic shifts, clinical demands, and policy decisions are presented, with an eye toward future trends in professional development. PMID- 26352040 TI - There's an "App" for That: Tips for Preparing Nurses for Roles in Mobile Health. AB - As health care services shift to being provided in the home and in the community, nurses must be prepared to use mobile health applications for diagnosis, monitoring, managing transitions of care, and health coaching. PMID- 26352041 TI - Advanced Beginner to Competent Practitioner: New Graduate Nurses' Perceptions of Strategies That Facilitate or Hinder Development. AB - BACKGROUND: New graduate nurses (NGNs) are a precious resource, but their development from advanced beginners to competent nurses is challenging. METHOD: This qualitative descriptive study explored NGNs' perceptions of strategies that influenced their development in the first 2 years of employment. Semistructured interviews were conducted with a sample of 13 nurses. RESULTS: The study revealed that NGNs learn to master aspects of the nursing role as they construct a professional identity. They identified organizational, educational, and personal strategies as being important to their development, including tailored orientation, opportunities for skill acquisition, and personal support. Few strategies supported the development of professional identity. CONCLUSION: Mastering the nursing role and constructing a professional identity is central to NGNs' development. Further attention from nursing leaders is needed to promote concurrent development in both dimensions. Nurses with a strong professional identity are more likely to remain in the profession. PMID- 26352043 TI - Dedicated Education Unit Model for a Transition Into Practice Course. AB - A dedicated education unit (DEU) model involves a collaborative partnership between a clinical agency and a school of nursing. This article describes the development of a DEU for a transition to practice course. No differences were noted in the satisfaction of students, staff nurses, and the clinical agency between the DEU and traditional preceptor models, but the DEU design enabled the school of nursing to place more students in the unit, compared with a preceptorship model. PMID- 26352044 TI - Supporting Graduate Nurse Transition: Collaboration Between Practice and University. AB - Making the transition from student to RN is challenging and demanding. In Australia, where nurses commonly graduate after 3 years in a Bachelor of Nursing program, graduate transition programs have been established in the workplace to support and socialize new graduates to nursing practice. These programs vary in content, rigor, and available support mechanisms, and no nationally agreed upon standards of expected graduate performance exist. Providing a structured, evidence-based, and clinically focused education and support program specific to the needs of graduate nurses contributes to quality care and patient safety and has significant benefits for the individual graduate, the employing organizations, and health care. This article presents the development and implementation of the Bachelor of Nursing With Clinical Honors (Transition to Practice) program offered by the University of Tasmania, in collaboration with St. Vincent's Private Hospital, Sydney, Australia. PMID- 26352045 TI - Effectiveness of an Online Caring Curriculum in Enhancing Nurses' Caring Behavior. AB - BACKGROUND: A hospital in Taiwan implemented a framework of caring in clinical practice. After the pilot study, the current study was conducted to implement and evaluate the effectiveness of the program. METHOD: One hundred four nurses from two hospitals were recruited for the intervention (n = 50) and comparison (n = 54) groups in a mixed-method, quasi-experimental pre- and postintervention design. Audiovisual materials based on the authentic caring and uncaring experiences of nurses and patients were created as the curriculum content. Role modeling and reflective practice were used as learning strategies. Both groups of nurses and patients completed a pre- and postintervention evaluation of nurse caring behaviors, using the SHARE (Sense patients' needs before they ask, Help patients out, Acknowledge patients' feelings, Respect the dignity and privacy of patients, Explain what is happening) caring behavior measurement. A focus group interview was conducted. RESULTS: The intervention group exhibited higher frequency of caring behavior than the comparison group (p < 0.001). CONCLUSION: Authentic experiences, reflective practice, and online videos were effective teaching strategies in enhancing nurse caring behavior in an online continuing education program. PMID- 26352046 TI - Subchronic Exposure of Mice to Cadmium Perturbs Their Hepatic Energy Metabolism and Gut Microbiome. AB - Cadmium (Cd) is an environmental pollutant known to cause liver damage; however, the mechanisms of its hepatotoxicity remain poorly understood. In this study, the effects of subchronic exposure in mice to low doses of Cd on energy metabolism and the gut microbiome were evaluated. The exposure of mice to 10 mg/L Cd supplied in drinking water for 10 weeks increased hepatic triacylglycerol (TG), serum free fatty acid (FFA), and TG levels. The mRNA levels of several key genes involved in both de novo FFA synthesis and transport pathways and in TG synthesis in the liver also increased significantly in the Cd-treated mice, indicating that alterations of these genes may be a possible mechanism to explain subchronic Cd exposure induced hepatic toxicity at a molecular level. As for the gut microbiome, at the phylum level, the amounts of Firmicutes and gamma proteobacteria decreased significantly in the feces after 4 weeks of Cd exposure, and the quantity of Firmicutes decreased significantly in the cecum contents after 10 weeks of Cd exposure. In addition, 16S rRNA gene sequencing further revealed that Cd exposure significantly perturbed the gut microflora structure and richness at family and genus levels. The alteration of gut microbiome composition might result in an increase in serum lipopolysaccharide (LPS) and induce hepatic inflammation, which may indirectly cause perturbations of energy homeostasis after Cd exposure. Taken together, the present study indicated that subchronic Cd exposure caused the dysregulation of energy metabolism and changed the gut microbiome composition in mice. PMID- 26352047 TI - Tin(II) Sulfide (SnS) Nanosheets by Liquid-Phase Exfoliation of Herzenbergite: IV VI Main Group Two-Dimensional Atomic Crystals. AB - The liquid-phase exfoliation of tin(II) sulfide to produce SnS nanosheets in N methyl-2-pyrrolidone is reported. The material is characterized by Raman spectroscopy, atomic force microscopy, lattice-resolution scanning transmission electron microscope imaging, and energy dispersive X-ray spectrum imaging. Quantum chemical calculations on the optoelectronic characteristics of bulk and 10-layer down to monolayer SnS have been performed using a quantum chemical density functional tight-binding approach. The optical properties of the SnS and centrifugally fractionated SnS nanosheet dispersions were compared to that predicted by theory. Through centrifugation, bilayer SnS nanosheets can be produced size-selectively. The scalable solution processing of semiconductor SnS nanosheets is the key to their commercial exploitation and is potentially an important step toward the realization of a future electronics industry based on two-dimensional materials. PMID- 26352049 TI - Vertical heterostructures of MoS2 and graphene nanoribbons grown by two-step chemical vapor deposition for high-gain photodetectors. AB - Heterostructures of two-dimensional (2D) layered materials have attracted growing interest due to their unique properties and possible applications in electronics, photonics, and energy. Reduction of the dimensionality from 2D to one-dimensional (1D), such as graphene nanoribbons (GNRs), is also interesting due to the electron confinement effect and unique edge effects. Here, we demonstrate a bottom-up approach to grow vertical heterostructures of MoS2 and GNRs by a two step chemical vapor deposition (CVD) method. Single-layer GNRs were first grown by ambient pressure CVD on an epitaxial Cu(100) film, followed by the second CVD process to grow MoS2 over the GNRs. The MoS2 layer was found to grow preferentially on the GNR surface, while the coverage could be further tuned by adjusting the growth conditions. The MoS2/GNR nanostructures show clear photosensitivity to visible light with an optical response much higher than that of a 2D MoS2/graphene heterostructure. The ability to grow a novel 1D heterostructure of layered materials by a bottom-up CVD approach will open up a new avenue to expand the dimensionality of the material synthesis and applications. PMID- 26352048 TI - Highly Dense Cu Nanowires for Low-Overpotential CO2 Reduction. AB - Electrochemical reduction of CO2, an artificial way of carbon recycling, represents one promising solution for energy and environmental sustainability. However, it is challenged by the lack of active and selective catalysts. Here, we report a two-step synthesis of highly dense Cu nanowires as advanced electrocatalysts for CO2 reduction. CuO nanowires were first grown by oxidation of Cu mesh in air and then reduced by either annealing in the presence of hydrogen or applying a cathodic electrochemical potential to produce Cu nanowires. The two reduction methods generated Cu nanowires with similar dimensions but distinct surface structures, which have provided an ideal platform for comparative studies of the effect of surface structure on the electrocatalytic properties. In particular, the Cu nanowires generated by electrochemical reduction were highly active and selective for CO2 reduction, requiring an overpotential of only 0.3 V to reach 1 mA/cm(2) electrode current density and achieving Faradaic efficiency toward CO as high as ~60%. Our work has advanced the understanding of the structure-property relationship of Cu-based nanocatalysts, which could be valuable for the further development of advanced electrocatalytic materials for CO2 reduction. PMID- 26352050 TI - Gas-Phase Retro-Diels-Alder Reactions of Cyclohexene, 1-Methylcyclohexene, and 4 Methylcyclohexene following Photoexcitation at 193 nm: A Velocity-Map Imaging Study. AB - We present the results of a velocity-map imaging study into the retro-Diels-Alder (RDA) reactions of cyclohexene, 1-methylcyclohexene, and 4-methylcyclohexene following photoexcitation at 193 nm. Universal detection of all neutral fragments via vacuum-ultraviolet photoionization at 118 nm allows imaging of both RDA fragments in all cases. Fragment kinetic energy distributions reveal contributions from both dissociative ionization and retro-Diels-Alder reaction of the respective parent molecules, yielding reaction products with a high degree of internal excitation. Together with the observed isotropic product angular distributions, this is consistent with a mechanism in which the RDA reaction occurs from high vibrational levels of the electronic ground state following internal conversion from a higher-lying state initially populated in the photoexcitation process, as predicted by frontier molecular orbital theory. Velocity-map images and total translational energy distributions for the RDA products of 1-methylcyclohexene and 4-methylcyclohexene are very similar to those for unsubstituted cyclohexene, indicating that methyl substitution either adjacent to or far from the double bond has little effect on the dynamics of the RDA process. PMID- 26352051 TI - Predicting solvent effects on the structure of porous organic molecules. AB - A computational approach for the prediction of the open, metastable, conformations of porous organic molecules in the presence of solvent is developed. PMID- 26352052 TI - On Field-Effect Photovoltaics: Gate Enhancement of the Power Conversion Efficiency in a Nanotube/Silicon-Nanowire Solar Cell. AB - Recent years have seen a resurgence of interest in crystalline silicon Schottky junction solar cells distinguished by the use of low density of electronic states (DOS) nanocarbons (nanotubes, graphene) as the metal contacting the Si. Recently, unprecedented modulation of the power conversion efficiency in a single material system has been demonstrated in such cells by the use of electronic gating. The gate field induced Fermi level shift in the low-DOS carbon serves to enhance the junction built-in potential, while a gate field induced inversion layer at the Si surface, in regions remote from the junction, keeps the photocarriers well separated there, avoiding recombination at surface traps and defects (a key loss mechanism). Here, we extend these results into the third dimension of a vertical Si nanowire array solar cell. A single wall carbon nanotube layer engineered to contact virtually each n-Si nanowire tip extracts the minority carriers, while an ionic liquid electrolytic gate drives the nanowire body into inversion. The enhanced light absorption of the vertical forest cell, at 100 mW/cm(2) AM1.5G illumination, results in a short-circuit current density of 35 mA/cm(2) and associated power conversion efficiency of 15%. These results highlight the use of local fields as opposed to surface passivation as a means of avoiding front surface recombination. A deleterious electrochemical reaction of the silicon due to the electrolyte gating is shown to be caused by oxygen/water entrained in the ionic liquid electrolyte. While encapsulation can avoid the issue, a nonencapsulation-based approach is also implemented. PMID- 26352054 TI - Type VI Collagen Regulates Dermal Matrix Assembly and Fibroblast Motility. AB - Type VI collagen is a non-fibrillar collagen expressed in many connective tissues and implicated in extracellular matrix (ECM) organisation. We hypothesized that type VI collagen regulates matrix assembly and cell function within the dermis of the skin. In the present study we examined the expression pattern of type VI collagen in normal and wounded skin and investigated its specific function in new matrix deposition by human dermal fibroblasts. Type VI collagen was expressed throughout the dermis of intact human skin, at the expanding margins of human keloid samples, and in the granulation tissue of newly deposited ECM in a mouse model of wound healing. Generation of cell derived matrices (CDMs) by human dermal fibroblasts with stable knockdown of COL6A1 revealed that type VI collagen deficient matrices were significantly thinner and contained more aligned, thicker, and widely spaced fibres than CDMs produced by normal fibroblasts. In addition, there was significantly less total collagen and sulfated proteoglycans present in the type VI collagen depleted matrices. Normal fibroblasts cultured on de-cellularised CDMs lacking type VI collagen displayed increased cell spreading, migration speed, and persistence. Taken together, these findings indicate that type VI collagen is a key regulator of dermal matrix assembly, composition, and fibroblast behaviour and may play an important role in wound healing and tissue regeneration.Journal of Investigative Dermatology accepted article preview online, 09 September 2015. doi:10.1038/jid.2015.352. PMID- 26352056 TI - Risk of Multiple Sclerosis in Patients with Psoriasis: A Danish Nationwide Cohort Study. AB - Psoriasis and multiple sclerosis (MS) are inflammatory disorders with similarities in genetic risk variants and inflammatory pathways. Limited evidence is available on the relationship between the two diseases. We therefore investigated the risk of incident (new-onset) MS in patients with mild and severe psoriasis, respectively. All Danish citizens aged >=18 years from January 1, 1997 to December 31, 2011 were identified by linkage of nationwide registries at the individual level. We estimated incidence rate ratios (IRRs) adjusted for age, gender, socio-economic status, smoking, medication, comorbidity, and ultraviolet phototherapy, by Poisson regression. There were 58,628 and 9,952 cases of mild and severe psoriasis, and 9,713 cases of MS, respectively. Incidence rates (IRs) of MS per 10,000 person years for the reference population, mild psoriasis, and severe psoriasis were 1.78, 3.22, and 4.55, respectively. Adjusted IRRs of MS were 1.84 (95% confidence interval [CI] 1.46 to 2.30), and 2.61 (95% CI 1.44 to 4.74) in mild and severe psoriasis, respectively. Similar results were observed when adjustment for family history of MS was included in the analyses. Psoriasis may confer a disease severity-dependent risk of MS. Further studies are warranted to establish the mechanisms underlying this relationship and its potential clinical consequences.Journal of Investigative Dermatology accepted article preview online, 09 September 2015. doi:10.1038/jid.2015.350. PMID- 26352057 TI - Antenatal risk factors for symptomatic congenital CMV disease following primary maternal CMV infection. AB - OBJECTIVES: This study aimed to evaluate antenatal risk factors associated with symptomatic congenital cytomegalovirus (CMV) disease, following in utero vertical infection. METHODS: This study included a retrospective cohort of 155 neonates with congenital CMV infection, following primary maternal CMV infection during pregnancy, and were divided to symptomatic (n=95) and asymptomatic (n=60) newborns. RESULTS: Young maternal age (29.1+/-5.12 vs. 31.6+/-5.36 years, P=0.005), high risk occupation for viral exposure (20.0% vs. 11.7%, P=0.04), CMV IgG seroconversion at diagnosis (83.1% vs. 63.3%, P=0.005) and abnormal fetal MRI (11.6% vs. 0%, P=0.003) were found to be prognostic risk factors associated with symptomatic CMV disease of the newborn. Maternal febrile illness at diagnosis, IgG avidity, US findings and the timing of maternal infection were not associated with the occurrence of neonatal symptoms. CONCLUSIONS: Knowledge of the reported risk factors may assist in counseling parents with intra uterine CMV infection. PMID- 26352058 TI - Adipokine, adropin and endothelin-1 levels in intrauterine growth restricted neonates and their mothers. AB - Intrauterine growth retardation/restriction (IUGR) is associated with fetal malnutrition. It has consequences for later life including increased incidence of obesity, diabetes mellitus, cardiovascular disease (CVD), and metabolic syndrome. Adipokines (adiponectin and leptin), adropin, and endothelin-1 are associated with obesity and metabolic syndrome regulation. Intrauterine changes in these mediators could affect programming of later adult obesity and metabolic syndrome. Our objectives were to compare the levels of these mediators in both cord and maternal blood between IUGR pregnancies and control, healthy pregnancies, and to study the correlation of adipokines with adropin and endothelin-1 in maternal and cord blood in IUGR pregnancies as well as in healthy control pregnancies. Maternal and cord blood samples were taken from 16 women with IUGR pregnancies and 16 women with healthy pregnancies. Serum levels of leptin, adiponectin, adropin, and endothelin-1 were measured by ELISA. Maternal blood adropin levels were significantly lower in the IUGR group than in the control group; the other mediators did not differ significantly. There was a positive correlation between maternal blood adropin and endothelin levels. (r=0.731, P=0.001) in the control but not the IUGR group. Cord blood adropin and adiponectin levels were significantly lower in the IUGR group compared with the control group, while leptin or endothelin-1 did not differ significantly. There was a negative correlation between adropin and leptin (r=-0.704, P=0.001) in the IUGR but not the control group cord blood. There were also positive correlations between endothelin and adropin for both groups (r=0.594, P=0.006; r=0.560, P=0.010, respectively); to the best of our knowledge, this is the first report of such a correlation. Differences in fetal expression of adropin and adiponectin in IUGR could influence programming of obesity, metabolic syndrome, diabetes, and CVD in later life. PMID- 26352059 TI - Cesarean delivery among women with prolonged labor induction. AB - OBJECTIVE: The objective of this study was to determine characteristics associated with cesarean delivery among women with labor induction lasting over 24 h. STUDY DESIGN: Women with live singleton pregnancies without prior cesarean delivery undergoing a labor induction lasting >24 h between September 2006 and March 2009 at Duke University Hospital were identified. Collected variables were compared between subjects by mode of delivery. A multivariate logistic regression model for the outcome cesarean delivery was constructed separately for nulliparous and parous women. RESULTS: There were 303 women who met inclusion criteria. The overall cesarean delivery rate was 57% (n=172) and remained constant with time (P=0.15, test-for-trend). Nulliparous women having a cesarean delivery were more likely to be obese [adjusted OR (aOR) 2.00; 95% CI 1.05, 3.80] and have a larger fetus [aOR 1.11 (aOR for every 100 g increase in birthweight), 95% CI 1.03, 1.20] compared to those having a vaginal delivery. CONCLUSION: Increasing BMI and birthweight were independent predictors of cesarean delivery among nulliparous women with prolonged labor induction. Despite this, after 24 h of labor induction, the overall mean cesarean delivery rate remained constant at 57%, and did not change with time. Among women having a vaginal delivery following a prolonged labor induction, we saw high rates of shoulder dystocia, operative vaginal delivery and severe perineal laceration. PMID- 26352060 TI - Preventing intellectual disability during pregnancy: what are the potentially high yield targets? AB - OBJECTIVE: To identify risk factors among children with unknown cause intellectual disability (ID) and to estimate the population-attributable risk (PAR) associated with these factors. METHODS: This was a retrospective cohort study of maternal and child pairs born between 2004 and 2010 in South Carolina, and information was obtained from Medicaid billing records, birth certificates, and other administrative data. The data included 123,922 children and logistic generalized estimating equations (GEE) regression models were used to estimate the association of maternal risk factors and ID. We estimated models with and without birth weight as a covariate, since low birth weight is known to be a mediator of the association between some risk factors and ID in children. RESULTS: The prevalence of ID in the children was 3.85% and the associations between risk factors and ID were similar for female and male children. We found that the odds of having ID were increased if a child's mother had a diagnosis of major depression; for male children, the odds ratio (OR) was 1.34 (95% confidence interval [CI] 1.14-1.59, PAR 2.17%); and for females, the OR was 1.59 (95% CI 1.30-1.95, PAR 4.70%). The odds of having ID were also increased for children of women with bipolar disorder (males - OR 1.95, 95% CI 1.53-2.48, PAR 2.85%; females - OR 1.63, 95% CI 1.20-2.22, PAR 2.05%). CONCLUSIONS: Major maternal depression and bipolar disorder were each significantly associated with the odds of ID in children, each accounting for approximately 2-5% of the PAR, when controlling for covariates. PMID- 26352061 TI - Association between decreased plasma levels of soluble human leukocyte antigen-G and severe pre-eclampsia. AB - OBJECTIVE: The aim of this study was to investigate the levels of different isoforms of soluble human leukocyte antigen-G (sHLA-G) in maternal plasma during early and late pregnancy, and to investigate the expression of sHLA-G isoforms in women with early or late-onset severe preeclampsia. METHODS: This prospective, nested, case-control study was performed in 24 early-onset severe preeclamptic, 34 late-onset severe preeclamptic, and 74 uncomplicated pregnant women. Plasma levels of sHLA-G1/5 were measured using ELISA. RESULTS: Plasma sHLA-G1 levels in women with late-onset severe preeclampsia were markedly lower compared with normal controls (median: 0 vs. 1.22 ng/mL) at the first trimester, and plasma sHLA-G1 levels in women with early-onset severe preeclampsia were markedly lower compared with normal controls at the second (median: 0 vs. 1.24 ng/mL) and third (median: 0 vs. 1.34 ng/mL) trimesters. There was no difference between the late onset and early-onset groups at three trimesters. As for sHLA-G5, there was no difference in concentrations among the three groups at any time point. However, compared with controls, more women with early- or late-onset severe preeclampsia had undetectable sHLA-G5 levels in the first (71.4% and 76.2% vs. 14.1%), second (75.0% and 73.3% vs. 19.0%), and third (100.0% and 70.4% vs. 14.8%, respectively) trimester (all P<0.05). sHLA-G1 levels in the first (odds ratio [OR]=0.254, 95% confidence interval [CI]=0.109-0.591, P=0.010), second (OR=0.315, 95% CI=0.158 0.627, P=0.001), and third (OR=0.170, 95% CI=0.054-0.533, P=0.002) trimester was a risk factor for severe preeclampsia. CONCLUSION: Severe preeclampsia was associated with low/undetectable maternal plasma levels of sHLA-G. Low sHLA-G1 levels might be a risk marker for severe preeclampsia. PMID- 26352062 TI - Music devices for the fetus? An evaluation of pregnancy music belts. AB - BACKGROUND: The implementation of music during pregnancy is a topic of interest for parents-to-be accompanied by a growing commercial interest. We evaluated acoustic properties of commercially available music devices. MATERIALS AND METHODS: Sound characteristics of three different music devices designed for fetal acoustical stimulation were analyzed. A white noise sample was presented at a high volume to produce a standardized acoustic stimulus. Sound emissions were registered for each loudspeaker with a sound level meter in order to document the sound pressure levels (SPLs) and to analyze the long-term averaged spectra (LTAS) with the help of PRAAT-sound-analyzing software. Measurements were conducted in open air and under attenuated conditions with interposition of a pork uterus of 5 mm thickness covered by porcine tissue from the abdominal wall of either 3 or 5 cm thickness. RESULTS: Under attenuated conditions, SPLs of all three devices were hardly detectable and interfered with the basal noise of around 50-55 dB (SPL), particularly low and high frequencies ranges were attenuated. CONCLUSION: Pregnancy music belts seem to be a useless tool to support fetal development. The poor sound characteristics of the loudspeakers and the concept of an isolated stimulation appear not promising to effectively support the complex multimodal maturation of the sensory system. Traditional implementation of music appears maternal singing appears more reasonable. PMID- 26352063 TI - Dopamine treatment does not need speed recovery of newborns from transient tachypnea. AB - OBJECTIVE: Transient tachypnea of the newborn (TTN) results from inadequate neonatal lung fluid clearance. Low-dose dopamine induces natriuresis in the kidneys and it has been assumed that, at this low dosage, dopamine increases renal perfusion in critically ill patients. Medium doses have positive inotropic and chronotropic effects via increased beta-receptor activation. Recent studies have demonstrated that dopamine stimulates the clearance of pulmonary edema. Furthermore, beta-adrenergic agonists regulate Na+ channels and Na-K-ATPase activity in the pulmonary epithelium. This study investigated the effect of dopamine at different dosages on TTN treatment. METHODS: A prospective controlled study examined 60 infants with TTN older than 34 weeks of gestation who required at least 24 h of O2 and nasal continuous positive airway pressure (nCPAP) treatment. The infants were randomized into three groups of 20: controls, infants treated with low-dose dopamine (3 MUg/kg/min), and infants treated with a medium dose (5 MUg/kg/min). The control and study groups were compared in terms of the requirement for mechanical ventilation, and the durations of nCPAP, oxygen requirement, and hospitalization. RESULTS: The requirement for mechanical ventilation, and durations of nCPAP, oxygen requirement, and hospitalization did not differ significantly among the three groups (P=0.54, 0.16 and 0.11, respectively). CONCLUSION: Dopamine treatment in low-moderate doses does not improve the outcome in TTN. Thus, further studies in this area are needed. PMID- 26352064 TI - The utility of clinical findings to predict laboratory values in hypertensive disorders of pregnancy. AB - OBJECTIVE: Preeclampsia is the 2nd leading cause of maternal mortality in the United States. Women with new-onset or worsening hypertension are commonly evaluated for laboratory abnormalities. We aim to investigate whether demographic and/or clinical findings correlate with abnormal laboratory values. STUDY DESIGN: A retrospective chart review of women who presented for evaluation of hypertension in pregnancy during 2010. Demographic information, medical history, symptoms, vital signs, and laboratory results were collected. Bivariate analysis was used to investigate associations between predictors and the outcome. RESULT: Of the 481 women in the sample, 22 were identified as having abnormal laboratory test results (4.6%). Women who reported right upper quadrant pain or tenderness had significantly increased likelihood of having laboratory abnormalities compared to those without the complaint. CONCLUSION: Only a small percentage of women evaluated were determined to have abnormal laboratory findings, predominantly among women with severe preeclampsia. Right upper quadrant pain or tenderness was positively correlated with laboratory abnormalities. The restriction of laboratory analysis in women with clinical evidence of severe disease may be warranted - a broader study should, however, first be used to confirm our findings. PMID- 26352065 TI - Maternal and perinatal outcomes after bariatric surgery: a case control study. AB - OBJECTIVE: To compare the results of maternal and perinatal pregnancies of obese women after bariatric surgery. METHODS: A retrospective cross-sectional study was carried out on 63 women who had undergone bariatric surgery and 73 obese women (control). Demographic data, the characteristics of the bariatric surgery, and the maternal and perinatal results were evaluated. The Student's t-test and chi square test (chi2) were used to compare the groups. The gestational complications of the prevalence of gestational diabetes mellitus, anemia, and preeclampsia were analyzed using simple and multivariate logistical regression and odd ratios (OD) with their respective confidence intervals (CI) of 95%. RESULTS: The average body mass index (BMI) at the 1st prenatal appointment of the control group was 34.6+/ 3.3 kg/m2 and that of the post-surgical group was 26.5+/-4.2 kg/m2. The Roux-en-Y Gastric Bypass was used in 100% of cases; no complications were observed during or after the surgeries. The average weight loss in patients with a prior bariatric surgery was statistically significant (P=0.000). The average weight at birth of the control group was significantly higher than in the post-bariatric surgery group (P=0.017). The women who had a prior bariatric surgery had a higher chance of anemia (OR=3.5; CI 95%: 1.5-8.3) and a reduced chance of macrosomia (OR=0.2; CI 95%:0.1-0.5), and prematurity (OR=0.3; CI 95%:0.1-0.7). CONCLUSION: Those women who had been submitted to bariatric surgery presented better maternal and perinatal results when compared to obese women. PMID- 26352066 TI - Effects of preeclampsia on the amplitude integrated electroencephalography activity in preterm infants. AB - OBJECTIVE: Preeclampsia leads to chronic intrauterine hypoxia by interfering with placental blood supply. The aim of this study was to investigate whether preeclampsia exposure has an influence on the central nervous system of infants, as monitored by amplitude integrated electroencephalography (aEEG). METHODS: We recruited 52 infants with gestational age between 30 and 34 weeks. Twenty-seven infants were born to preeclamptic mothers, and 25 gestational age-matched infants whose mothers were healthy were enrolled as a control group. aEEG recordings were performed between 24 and 48 h of life using a cerebral function monitor (CFM) (Olympic Brainz monitor). Along with aEEG, middle cerebral artery (MCA) blood flow velocities (BFV) were measured using Doppler ultrasound. RESULTS: The duration of quiet sleep was significantly shorter (P=0.001), and Burdjalov score was lower (P=0.04) in the preeclampsia group. However, there was no change in MCA BFV in this group. CONCLUSIONS: Preeclampsia altered cerebral electrical activity of premature infants born to preeclamptic mothers. PMID- 26352067 TI - Maternal and fetal outcomes after uterine fundal pressure in spontaneous and assisted vaginal deliveries. AB - AIM: This study aimed to evaluate maternal and fetal outcomes after uterine fundal pressure (UFP) in spontaneous and assisted vaginal deliveries. METHODS: In a retrospective cohort study, 9743 singleton term deliveries with cephalic presentation were analyzed from 2004 to 2013. Spontaneous and assisted vaginal deliveries were analyzed separately with and without the application of UFP. Odds ratios were adjusted in a multivariate logistic regression analysis. RESULTS: Prevalence of UFP was 8.9% in spontaneous and 12.1% in assisted vaginal deliveries. UFP was associated with a higher incidence of shoulder dystocia in both spontaneous (adjusted odds ratio [adj. OR] 2.44, confidence interval [CI] 95% 1.23-4.84) and assisted vaginal deliveries (adj. OR 6.88 CI 95% 3.50-13.53). Fetal acidosis (arterial umbilical pH<7.2) was seen more often after the application of UFP in spontaneous vaginal deliveries (adj. OR 3.18, CI 95% 2.64 3.82) and assisted vaginal deliveries (adj. OR 1.59 CI 95% 1.17-2.16). The incidence of 5'-Apgar<7 (adj. OR 2.19 CI 95% 1.04-4.6) and 10'-Apgar<7 (adj. OR 3.04 CI 95% 1.17-7.88) was also increased after the application of UFP in spontaneous deliveries. A higher incidence of anal sphincter tears (AST) (adj. OR 46.25 CI 95% 11.78-181.6) in the UFP group of spontaneous deliveries was observed. CONCLUSIONS: UFP is associated with increased occurrence of shoulder dystocia and fetal acidosis. In spontaneous deliveries, the risk for lower Apgar scores after 5 and 10 min is increased, as well as the risk for AST. PMID- 26352069 TI - The impact of uterine curettage postpartum on maternal sFlt-1 concentration. AB - Our purpose was to investigate the influence of a uterine curettage on the immediate maternal sFlt-1 concentration post partum. Forty-six patients booked for delivery via primary caesarean section were included in a prospective open, case control study. Eighteen of them achieved an intraoperative curettage and formed the treatment group, 28 patients without curettage were enrolled in the control group. Maternal sFlt-1 serum values were measured immediately before and 24 h after delivery. Patients who underwent a uterine curettage showed a relative decrease of 70% (median 3670+/-1110 pg/mL-1143+/-270 pg/mL) in comparison to the control group with 65% (median 3132+/-636 pg/mL-1098+/-611 pg/mL; P=0.558). Additionally, three patients with preeclampsia and curettage were included, who showed a relative decrease of 76%. A uterine curettage may slightly accelerate the fall of the postpartal sFlt-1 concentration. The previously described benefit of curettage in patients with preeclampsia regarding faster recovery or treatment of postpartum seizures may be partly explained as mediated by anti-angiogenic factors. PMID- 26352070 TI - The relationship between cesarean section rate in term singleton pregnancies, maternal weight, and weight gain during pregnancy. AB - OBJECTIVE: Pregravid maternal weight and appropriate weight gain during pregnancy might be associated with increased cesarean section rate. STUDY DESIGN: We used data from the Slovenian National Perinatal Information System to select singleton pregnancies born at >=38 weeks, during the period between 2003 and 2012. We calculated the frequencies of urgent and elective cesarean sections (UCS and ECS, respectively) in mothers who gained less than, more than, and as recommended by the Institute of Medicine (IOM) according to their pregravid body mass index (BMI). RESULTS: The analysis included 170,121 women who delivered singletons >=38 weeks. A total of 24,327 (14.3%) women underwent cesarean section: 14,692 (8.6%) UCS and 9635 (5.7%) ECS. The frequency of cesareans, both UCS and ECS, increases as BMI increases irrespective of weight gain pattern. The frequency of urgent cesareans in all women increases and that of elective cesareans among obese women decreases as the level of weight gain increases from undergainers to overgainers. CONCLUSION: The combination of pregravid BMI and weight gain pattern is an important determinant of cesarean section rates at term. PMID- 26352072 TI - Increased levels of serum clusterin is associated with intrauterine growth restriction and adverse pregnancy outcomes in preeclampsia. AB - AIM: Our aim was to investigate serum clusterin levels in preeclampsia and to determine whether any changes in clusterin levels are useful in distinguishing the presence of concomitant intrauterine growth restriction (IUGR) and in predicting adverse pregnancy outcomes. METHODS: A prospective case-control study was carried out which included 86 pregnant women (47 patients with preeclampsia and 39 healthy controls). Maternal serum samples obtained from all participants and clusterin levels were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared with controls, women with preeclampsia had significantly higher clusterin levels (mean 83.8+/-23.6 vs. 119.2+/-40.5, P<0.01). Further analysis revealed the highest clusterin levels were in patients with preeclampsia and IUGR (P<0.001). According to the receiver operating characteristic (ROC) analysis performed for the predictive value of clusterin levels for adverse maternal outcomes, the area under the curve (AUC) was 0.738 (95% CI: 0.616-0.859). The best clusterin cut-off value in predicting adverse maternal outcomes was 102.6 pg/mL with 75% sensitivity and 66% specifity. Multivariable logistic regression analysis revealed serum clusterin levels of >102.6 pg/mL was independently associated with preeclampsia (OR: 6.18, 95% CI: 2.41-15.9) and maternal adverse outcomes (OR: 5.13, 95% CI: 2.01-13.1) and also clusterin levels higher than 117.4 pg/mL were associated with adverse neonatal outcomes (OR: 5.02, 95% CI: 1.04-24.3). CONCLUSIONS: The current study suggests that increased levels of clusterin is associated with IUGR and probably predictive for adverse pregnancy outcomes in preeclampsia. PMID- 26352073 TI - Does progesterone administration in preterm labor influence Treg cells? AB - OBJECTIVES: The aim of this study was to determine if the actions of progesterone on preterm labor are accomplished through modulation of the percentage of regulatory T-cells (Treg). METHODS: The study was a cohort pilot study made in a single center tertiary obstetrical unit with women in preterm labor arrested with tocolytic treatment. Variation of the number and percentage of Treg cells obtained from peripheral blood samples of women with preterm labor were calculated by flow cytometry, before and after progesterone administration. RESULTS: In the paired samples for each patient, there was a significant difference in the Treg cell pool after progesterone treatment, with an increase in both their percentage (48.9 vs. 53; P=0.07) and absolute number (14.8 vs. 56.5 cells/MUL; P=0.046). CONCLUSIONS: This research demonstrated a considerable increase in the Treg cell pool after progesterone treatment. This indicates a possible mechanism for progesterone treatment benefits in preterm labor, potentially increasing its more rational use. PMID- 26352074 TI - Reliability of posterior-left atrium space index measurements during 20-24 weeks of gestation in structurally normal fetuses. AB - OBJECTIVE: We aimed to evaluate the correlation between clinical parameters and the post-left atrium (LA) space index, which is a candidate screening marker for total anomalous pulmonary venous connection (TAPVC). We also calculated the inter and intra-observer variabilities of measurements for this parameter. METHODS: The LA-descending aorta distance/descending aorta diameter ratios (post-LA space index) were obtained from 165 fetuses between 20 and 24 weeks of gestation. Regression analyses were utilized to evaluate the correlations across clinical parameters and the post-LA space index. Intraclass correlations coefficients were calculated for the intra- and inter-observer agreements of three examiners with different sonographic experience. RESULTS: The mean (+/-SD) maternal and gestational age (GA) was 28.6+/-4.9 years and 21.7+/-0.9 weeks of gestation, respectively. In multivariate analyses, there was no correlation between post-LA space index and maternal age, fetal gender, or GA at cardiac scan. There were moderate to strong correlations across the measurements by different examiners, indicating good inter- and intra-observer agreements. CONCLUSION: The post-LA space index during 20-24 weeks of gestation is a simple and reliable marker that is not affected by GA. However, its potential as a screening tool for TAPVC warrants further clinical investigation. PMID- 26352068 TI - Clinical chorioamnionitis at term IV: the maternal plasma cytokine profile. AB - INTRODUCTION: Fever is a major criterion for clinical chorioamnionitis; yet, many patients with intrapartum fever do not have demonstrable intra-amniotic infection. Some cytokines, such as interleukin (IL)-1, IL-6, interferon-gamma (IFN-gamma), and tumor necrosis factor alpha (TNF-alpha), can induce a fever. The objective of this study was to determine whether maternal plasma concentrations of cytokines could be of value in the identification of patients with the diagnosis of clinical chorioamnionitis at term who have microbial-associated intra-amniotic inflammation. METHODS: A retrospective cross-sectional study was conducted, including patients with clinical chorioamnionitis at term (n=41; cases) and women in spontaneous labor at term without clinical chorioamnionitis (n=77; controls). Women with clinical chorioamnionitis were classified into three groups according to the results of amniotic fluid culture, broad-range polymerase chain reaction coupled with electrospray ionization mass spectrometry (PCR/ESI MS), and amniotic fluid IL-6 concentration: 1) no intra-amniotic inflammation; 2) intra-amniotic inflammation without detectable microorganisms; or 3) microbial associated intra-amniotic inflammation. The maternal plasma concentrations of 29 cytokines were determined with sensitive and specific V-PLEX immunoassays. Nonparametric statistical methods were used for analysis, adjusting for a false discovery rate of 5%. RESULTS: 1) The maternal plasma concentrations of pyrogenic cytokines (IL-1beta, IL-2, IL-6, IFN-gamma, and TNF-alpha) were significantly higher in patients with clinical chorioamnionitis at term than in those with spontaneous term labor without clinical chorioamnionitis; 2) the maternal plasma concentrations of cytokines were not significantly different among the three subgroups of patients with clinical chorioamnionitis (intra-amniotic inflammation with and without detectable bacteria and those without intra-amniotic inflammation); and 3) among women with the diagnosis of clinical chorioamnionitis, but without evidence of intra-amniotic inflammation, the maternal plasma concentrations of pyrogenic cytokines were significantly higher than in patients with spontaneous labor at term. These observations suggest that a fever can be mediated by increased circulating concentrations of these cytokines, despite the absence of a local intra-amniotic inflammatory response. CONCLUSIONS: 1) The maternal plasma concentrations of pyrogenic cytokines (e.g. IL-1beta, IL-2, IL-6, IFN-gamma, and TNF-alpha) are higher in patients with intra partum fever and the diagnosis of clinical chorioamnionitis at term than in those in spontaneous labor at term without a fever; and 2) maternal plasma cytokine concentrations have limited value in the identification of patients with bacteria in the amniotic cavity. Accurate assessment of the presence of intra-amniotic infection requires amniotic fluid analysis. PMID- 26352075 TI - Pregnancy outcome and long-term follow-up of fetuses with isolated increased NT: a retrospective cohort study. AB - OBJECTIVE: To assess the prevalence of associated findings, diagnosed either prior to or after birth, among fetuses with increased nuchal translucency (NT) and normal karyotype and to investigate the prevalence of children under therapy at school age, among cases confirmed to be isolated both prior to and after birth. METHODS: Retrospective cohort study of all singleton pregnancies were referred for the 1st trimester screening for Down syndrome between January 2004 and December 2006. Cases with NT >95th percentiles who undertook fetal karyotype were analyzed. We evaluated the prevalence of the following: (i) abnormal fetal karyotype, (ii) associated structural abnormalities, (iii) genetic syndromes, and (iv) children needing treatment (i.e. medications or psychopedagogical intervention) at school age. RESULTS: There were 19 106 women screened for Down syndrome. Among them, 846 (4.4%) had a NT >95th centile, of whom 541 (64.0%) undertook fetal karyotyping, 422 (78.0%) had normal karyotype, two (0.5%) opted for termination of pregnancy, and four (1.0%) ended in miscarriages. Among the 384 cases thought to be "normal" prior to birth, 14 (3.6%) were lost at follow-up and 10 (2.7%) had an associated abnormality diagnosed postnatally. Among the cases confirmed to be isolated, 10/270 (3.7%) were under treatment at the time of telephonic interview with parents. CONCLUSIONS: Parents should be informed that fetuses with increased NT and normal karyotype need detailed ultrasound scans during pregnancy and detailed pediatric evaluation at birth; if these are normal, the risk from adverse outcome at school age is the same as for general population. PMID- 26352076 TI - Is there any relationship between serum sirtuin-1 level and neutrophil-lymphocyte ratio in hyperemesis gravidarum? AB - AIM: The aim of this study was to evaluate the relationship between serum sirtuin 1 (SIRT1) level and neutrophil-lymphocyte ratio (NLR) with hyperemesis gravidarum (HG). METHODS: Overall, 90 patients who presented with pregnancy between August 2013 and November 2014 were included in the study. The patients were divided into two groups: patients with HG (n=45) and patients without HG (control group [C]; n=45). The patients with comorbid conditions other than pregnancy (disease or medication) were excluded. In all patients, demographic data including age, body mass index (BMI), gestational week, and smoking status were recorded. Blood samples were drawn for complete blood count and measurements of blood lipid, liver enzymes, serum SIRT1, and insulin levels. NLR was calculated from CBC. RESULTS: No significant differences were detected in age, BMI, or GA between groups (P>0.05). Serum SIRT1 and NLR were found to be significantly higher in patients with HG compared with those in the control group (P=0.001 and 0.006, respectively). CONCLUSION: In HG, both SIRT1 level and NLR increased. In HG, this occurred as a response to metabolic alterations and potential inflammation. PMID- 26352071 TI - Clinical chorioamnionitis at term VI: acute chorioamnionitis and funisitis according to the presence or absence of microorganisms and inflammation in the amniotic cavity. AB - OBJECTIVE: Neonates born to mothers with clinical chorioamnionitis at term are at an increased risk of infection. Acute subchorionitis, chorioamnionitis, and funisitis are considered placental histologic features consistent with acute inflammation according to the Society for Pediatric Pathology. The objectives of this study were to examine the performance of placental histologic features in the identification of: 1) microbial-associated intra-amniotic inflammation (intra amniotic infection); and 2) fetal inflammatory response syndrome (FIRS). METHODS: This retrospective cohort study included women with the diagnosis of clinical chorioamnionitis at term (n=45), who underwent an amniocentesis to determine: 1) the presence of microorganisms using both cultivation and molecular biologic techniques [polymerase chain reaction (PCR) with broad range primers]; and 2) interleukin (IL)-6 concentrations by enzyme-linked immunosorbent assay (ELISA). The diagnostic performance (sensitivity, specificity, accuracy, and likelihood ratios) of placental histologic features consistent with acute inflammation was determined for the identification of microbial-associated intra-amniotic inflammation and FIRS. RESULTS: 1) The presence of acute histologic chorioamnionitis and funisitis was associated with the presence of proven intra amniotic infection assessed by amniotic fluid analysis; 2) funisitis was also associated with the presence of FIRS; 3) the negative predictive value of acute funisitis >=stage 2 for the identification of neonates born to mothers with intra amniotic infection was <50%, and therefore, suboptimal to exclude fetal exposure to bacteria in the amniotic cavity; and 4) acute funisitis >=stage 2 had a negative predictive value of 86.8% for the identification of FIRS in a population with a prevalence of 20%. CONCLUSION: Acute histologic chorioamnionitis and funisitis are associated with intra-amniotic infection and the presence of FIRS. However, current pathologic methods have limitations in the identification of the fetus exposed to microorganisms present in the amniotic cavity. Further studies are thus required to determine whether molecular markers can enhance the performance of placental pathology in the identification of neonates at risk for neonatal sepsis. PMID- 26352077 TI - Effect of antenatal betamethasone administration on Doppler velocimetry of fetal and uteroplacental vessels: a prospective study. AB - OBJECTIVES: To examine the effect of antenatal betamethasone administration on Doppler parameters of fetal and uteroplacental circulation. METHODS: Seventy-six singleton pregnancies that received betamethasone therapy were prospectively evaluated. Doppler measurements of pulsatility indices (PI) in fetal umbilical artery (UA), middle cerebral artery (MCA), ductus venosus and maternal uterine arteries were performed before (0 h) and 24, 48, 72 and 96 h after the first dose of betamethasone. Women with positive end-diastolic flow (EDF) in UA and those with absent or reversed EDF in UA were evaluated separately. RESULTS: Fifty-two women with EDF in UA and 24 women with absent or reversed flow in UA were examined. Administration of maternal betamethasone was followed by a significant decrease in the PI of the MCA at 24 h (P<0.05). Additionally, return of absent to positive, reversed to absent or from reversed to positive diastolic flow in UA was detected within 24 h in 19 (79.2%) fetuses with absent or reversed UA-EDF. All alterations were transient and maintained up to 72 h. CONCLUSIONS: Antenatal administration of betamethasone is associated with significant but transient changes in the fetal blood flow. Hence, intensive surveillance of fetuses with Doppler ultrasonography is warranted following betamethasone therapy. PMID- 26352078 TI - Factors associated with choice of delivery with or without epidural analgesia among laboring women: a cross-sectional survey at a tertiary care hospital of a developing country. AB - AIMS: The aim of this study was to evaluate the factors responsible for epidural analgesia (EA) refusal among parturient patients. METHODS: In this prospective cross-sectional study of six months, we included all consenting postpartum patients having a non-operative delivery in the obstetric unit of our hospital. Data were collected on a predesigned questionnaire and included information such as parity, education, reasons for delivering with or without EA, source of information and patient satisfaction. Knowledge regarding EA was assessed from patients delivering without EA. RESULTS: From 933 patients enrolled, 730 (78.2%) delivered without EA, and 203 (21.7%) with EA. Only 11 (1.5%) patients refused EA for the reason of having natural birth process. Otherwise common reasons were misconceptions (65.9%) and lack of awareness about EA (20.5%); 70.5% had no knowledge of common side effects of EA. Among patients delivering with EA, 92.6% were offered EA by health care providers and had obstetricians and anesthesiologists as their sources of information. CONCLUSIONS: Patients in developing countries are laboring without EA, even in centers where there is a provision for it. The main reasons for not availing themselves of EA are lack of awareness and knowledge and misconceptions, rather than the desire to have un medicated natural birth. PMID- 26352079 TI - Randomized control trial comparing physiologic effects in preterm infants during treatment with nasal continuous positive airway pressure (NCPAP) generated by Bubble NCPAP and Ventilator NCPAP: a pilot study. AB - OBJECTIVES: Nasal continuous positive airway pressure (NCPAP) is an accepted form of non-invasive ventilation in preterm infants. Few, if any, studies have shown an advantage of one type of NCPAP over another. It has been theorized that bubble generated NCPAP may be advantageous for the preterm neonate versus traditionally used ventilator-generated NCPAP. The aim of this study was to examine for any short-term differences in physiologic parameters in preterm subjects receiving these two different methods of NCPAP. METHODS: We conducted a randomized, prospective, cross-over pilot study of preterm infants being treated with NCPAP in the neonatal intensive care unit. Subjects were continuously monitored for several physiologic parameters including heart rate, respiratory rate, oxygen saturation, cerebral tissue oxygen saturation and cerebral fractional oxygen extraction using routine neonatal monitors and near-infrared spectroscopy (NIRS) while on 2 h of bubble NCPAP and 2 h of ventilator NCPAP. Subjects were randomized to be monitored while either starting on bubble NCPAP and then switching to ventilator NCPAP or starting on ventilator NCPAP and switching to bubble NCPAP. RESULTS: Eighteen subjects were included. We found no statistically significant difference in any of the physiologic parameters while subjects were receiving bubble NCPAP versus ventilator NCPAP during the monitoring time periods. While on bubble NCPAP, subjects showed a trend toward decreasing respiratory rate and decreasing cerebral fractional oxygen extraction over time, but this did not reach statistical significance. CONCLUSION: There appears to be no difference in immediate physiologic effects between bubble NCPAP and ventilator NCPAP. This does not preclude the possibility of potential long-term differences, but any differences seen would likely be based on mechanisms that take more time to develop. A larger prospective trial is warranted to confirm our findings. PMID- 26352080 TI - Clinical characteristics and factors associated with term and late preterm infants that do not respond to inhaled nitric oxide (iNO). AB - AIM: Inhaled nitric oxide (iNO) is used to treat neonates with hypoxic respiratory failure (HRF). The aim of this study was to determine clinical characteristics and factors associated with non-response to iNO therapy that may assist in clinical management and weaning strategies. METHODS: Retrospective chart review. The study cohort included gestational age >=34 weeks' infants with acute HRF who received iNO within 7 days of birth. Subjects were stratified as responders or non-responders to iNO. Non-responders were defined as infants with failure to improve their PaO2 >20 mm Hg within 6 h of iNO initiation, need for extracorporeal membrane oxygenation (ECMO), or mortality. Clinical and laboratory characteristics were then compared between groups. RESULTS: Forty four subjects were included. There were 31 responders and 13 non-responders to iNO therapy. Regression analysis showed significant correlation between a non-response to iNO therapy and changes in PaO2 and pH levels. We found for every 10 mm Hg decrease in PaO2 immediate post-iNO therapy there is a 17.5% decrease in the likelihood of responding to iNO (odds ratio [OR] 0.98, P=0.012). Similarly, for every 0.15 point decrease in pH, there is a 16.3% increased chance of not responding to iNO therapy (OR 1.16, P=0.002). The need for pressor support prior to iNO initiation was also found to be associated with a non-response (OR 2. 94, P=0.034). CONCLUSIONS: Hypotension requiring treatment with pressors at the time of iNO therapy, as well as changes in pH and PaO2 after iNO initiation can be used as early clinical predictors to identify patients quickly who may be iNO non responders. PMID- 26352081 TI - Essential oils reduce autonomous response to pain sensation during self monitoring of blood glucose among children with diabetes. AB - BACKGROUND: Essential oils were proven to possess analgesic activity in adults. Children with diabetes are exposed to highly painful interventions such as self monitoring of blood glucose (SMBG). OBJECTIVE: An evaluation of the analgesic properties of two essential oils during SMBG in diabetic children. SUBJECTS: We included 73 hospitalized children (age<18 years) with well-controlled type 1 diabetes. METHODS: The study extended over a period of 1 month (2 weeks for control group and 1 week for orange and lavender oil application). The measurements were performed four times per day in a shared room during SMBG. Pain intensity was evaluated by visual analog scale (VAS) and change of baseline heart rate (DeltaHR%). An aromatherapy device was used to disperse essential oils in the testing room. RESULTS: We performed 647 individual measurements of pain intensity and DeltaHR%. Girls reported higher VAS scores [median, Me 0.5 (interquartile range, IQR 0-1) vs. 0 (IQR 0-0.5), p=0.0036]. Both age and duration of diabetes correlated with DeltaHR% [r=-0.14, p=0.0005; r=-0.12, p=0.0025]. Negative correlations were also noted for VAS/age [r=-0.12, p=0.0030] and VAS/duration of diabetes [r=-0.12, p=0.0034]. Aromatherapy did not alter the VAS score (p=0.40), while DeltaHR% decreased with borderline significance (p=0.0639). After adjustment for patient's age and sex lower DeltaHR% was associated with essential oil application (p=0.0252). Aromatherapy did not have any influence on VAS scores in multivariate analysis (p=0.35). CONCLUSION: Aromatherapy decreased the autonomic response to a painful stimulus by lowering DeltaHR%, but did not affect the perception of pain reported by VAS. PMID- 26352082 TI - Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation syndrome and celiac disease in a 13-year-old girl: further evidence for autoimmunity? AB - Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) syndrome is a rare and potentially lethal disorder. The etiology is unclear but paraneoplastic syndrome and autoimmunity secondary to neural crest tumors have been considered, even in patients without any detectable tumor due to their tendency for spontaneous remission. We are presenting a 13 year-old girl with ROHHAD syndrome and celiac disease, which may suggest further evidence for immune-mediated etiology in the pathogenesis of ROHHAD syndrome. PMID- 26352083 TI - Marked phenotypic variable expression among brothers with duplication of Xq27.1 involving the SOX3 gene. AB - We describe four phenotypically different brothers who share the same microduplication of Xq27.1, which contains the SOX3 gene. SOX3 mutations have been associated with growth hormone deficiency, variable degrees of additional pituitary hormone deficiencies, and mental retardation. SOX3 also appears to play an important role in pharyngeal arch segmentation that gives rise to craniofacial structures. While these four brothers have inherited the same mutation, they manifest a spectrum of phenotypes, ranging from complete, multiple pituitary hormone deficiencies to no apparent pituitary hormone deficiency with or without craniopharyngeal/facial dysmorphisms. We look to the literature to provide putative explanations for the variable expression of the brothers' shared SOX3 mutation. PMID- 26352084 TI - Effect of auditory guided imagery on glucose levels and on glycemic control in children with type 1 diabetes mellitus. AB - BACKGROUND: To assess the effect of auditory guided imagery (AGI) on glucose levels, glycated hemoglobin (HbA1c), and quality of life (QOL) in type 1 diabetes mellitus children. METHODS: A blinded randomized controlled study comparing the effect of AGI accompanied by background music and background music solely (BMS). The study included 13 children, (7-16 years). The participants were connected to continuous glucose monitoring system for 5 days (short phase), and the outcome measure was the change in mean interstitial glucose concentration (IGC). Participants listened to the recording twice a week for 12 weeks (long phase), and the outcome measures were changes in QOL and in HbA1c. RESULTS: Mean IGC decreased in both AGI and BMS groups while listening. HbA1c decreased in both groups, but the decrease in the AGI group was significant. CONCLUSION: Listening to AGI is a potential approach for improving glycemic control and glucose levels in youth with T1DM, but further research is required. PMID- 26352085 TI - Use of the triglyceride to HDL cholesterol ratio for assessing insulin sensitivity in overweight and obese children in rural Appalachia. AB - BACKGROUND: Studies have suggested that triglyceride to HDL-cholesterol ratio (TRG/HDL) is a surrogate marker of insulin resistance (IR), but information regarding its use in pediatric patients is limited. This study investigated the ability of TRG/HDL ratio to assess IR in obese and overweight children. METHODS: The sample consisted of de-identified electronic medical records of patients aged 10-17 years (n=223). Logistic regression was performed using TRG/HDL ratio as a predictor of hyperinsulinemia or IR defined using homeostasis model assessment score. RESULTS: TRG/HDL ratio had limited ability to predict hyperinsulinemia (AUROC 0.71) or IR (AUROC 0.72). Although females had higher insulin levels, male patients were significantly more likely to have hypertriglyceridemia and impaired fasting glucose. CONCLUSIONS: TRG/HDL ratio was not adequate for predicting IR in this population. Gender differences in the development of obesity-related metabolic abnormalities may impact the choice of screening studies in pediatric patients. PMID- 26352086 TI - Effects of methylphenidate on appetite and growth in children diagnosed with attention deficit and hyperactivity disorder. AB - The purpose of this study was to determine the levels of leptin, ghrelin, and nesfatin-1 to elucidate the causes of poor appetite and growth retardation in patients receiving methylphenidate therapy for attention deficit hyperactivity disorder. The study was performed on 89 male subjects; 48 patients and 41 healthy controls, aged 7-14 years. Following treatment, patients' leptin levels increased and ghrelin levels decreased while no significant change was found in nesfatin-1 levels. Of the 48 patients, 34 developed lack of appetite. In patients who developed lack of appetite, body weight SDS, body mass index (BMI), and BMI SDS were statistically significantly reduced; moreover, height SDS was reduced, though not to a statistically significant extent. This study attempted to elucidate the mechanisms that mediate the association between methylphenidate and appetite and growth, for which no studies have yet to be published. PMID- 26352087 TI - Topical dihydrotestosterone to treat micropenis secondary to partial androgen insensitivity syndrome (PAIS) before, during, and after puberty - a case series. AB - BACKGROUND: X-linked partial androgen insensitivity syndrome (PAIS) causes under virilization at all stages of development. In two thirds of males, this results in micropenis. Dihydrotestosterone (DHT) is a potent androgen that is critical for male genital development, which when applied topically, has been shown to increase penile length with micropenis of varying etiologies. We present the first case series using topical DHT gel to treat micropenis in 46,XY males with PAIS, before, during, and after puberty. METHODS: Three related 46,XY males with confirmed p.L712F androgen receptor mutations exhibited varying degrees of micropenis post-surgical correction. They were of pre-pubertal, peri-pubertal and adult ages, respectively. Following baseline clinical and laboratory assessments all completed a 4-month course of daily DHT gel 2.5% (androstanolone) topically to penis (0.3 mg/kg body weight), with monitoring for adverse effects. Primary outcome was change in stretched penile length (SPL) following treatment. RESULTS: Mixed results were obtained following topical DHT therapy. In the pre- and peri- pubertal patients, SPL changed from 2.5 cm to 3.5 cm (+40%), and 3.5 cm to 5.7 cm (+63%), respectively. In the adult patient with 1 year of prior high-dose weekly testosterone therapy, no additional change in SPL was seen. No adverse effects of topical DHT were reported or observed throughout the 4 months of treatment. CONCLUSIONS: Topical DHT treatment appears to be a safe and well-tolerated method of virilising micropenis both prior to and during puberty in children with PAIS. Questions remain about long-term outcomes into adulthood, and efficacy in adults with prior lengthy exposure to high-dose testosterone. PMID- 26352088 TI - Vulvar fetal rhabdomyoma mimicking 46XX sex differentiation disorder. AB - Rhabdomiomas are rare mesenchymal benign tumors of striated muscle origin. Setting aside the cardiac (most atrial) rhabdomiomas typically associated to neurocutaneous syndromes (tuberous sclerosis), extracardiac rhabdomyomas appear clinically as a subcutaneous nodule or as a submucosal polypoid lesion. Among them, three main histologic subtypes can be differentiated on the basis of the degree of tumor differentiation: 1) fetal rhabdomioma, usually diagnosed during childhood and almost exclusively located in the in the head and neck region with rare reports in other locations; 2) adult rhabdomioma; and 3) genital rhabdomioma, reported to occur in the lower genital tract of young and middle aged women and, exceptionally, in children (5). PMID- 26352089 TI - Low serum sclerostin levels in newborns with vitamin D deficiency. AB - BACKGROUND: Sclerostin is a glycoprotein produced by osteocytes that is being evaluated as a potential clinical marker of bone turnover. The aim of this study was to investigate the association between neonatal vitamin D status and levels of circulating sclerostin. METHODS: Forty newborns were recruited for the study. Vitamin D deficiency was defined as a serum 25-hydroxyvitamin D3 [25(OH)D] concentration <20 ng/mL and the newborns were divided into two groups as vitamin D deficient and vitamin D sufficient groups. Calcium, phosphate, alkaline phosphatase and sclerostin were measured at birth. RESULTS: Newborns with vitamin D deficiency had markedly lower 25(OH)D levels than vitamin D sufficient newborns (8.5+/-4.4 ng/mL vs. 35.3+/-10.6 ng/mL, p<0.001). Vitamin D deficient infants also had significantly lower serum sclerostin levels (188.4+/-21.9 vs. 282.3+/ 30.4 pg/mL; p: 0.026) than vitamin D sufficient newborns at birth. However, we did not detect a significant linear association between neonatal sclerostin and maternal/neonatal 25(OH)D levels. CONCLUSIONS: Our data also demonstrated that vitamin D deficient newborns exhibited lower sclerostin levels than vitamin D sufficient newborns. The low sclerostin level might serve as a marker of decreased osteocyte activity in newborns with vitamin D deficiency. PMID- 26352090 TI - Anti-diabetic effects of aqueous prickly lettuce (Lactuca scariola Linn.) leaves extract in alloxan-induced male diabetic rats treated with nickel (II). AB - BACKGROUND: Hattaraki pallye or prickly lettuce (Lactuca scariola Linn.) is one among several green leafy plants that grow in north Karnataka; it is usually consumed by the people of this region and is found to be antidiabetic in nature. The objective of this study is to evaluate hypoglycemic activities of supplementation with aqueous extract of prickly lettuce (L. scariola) leaves in vivo in acute and subchronic exposure with or without nickel (II) along with its glucose reduction capabilities with or without nickel (II) at pH 7.0 and 9.0 in vitro. METHODS: Percentage glucose reduction (in vitro) was determined by glucose oxidase-peroxidase enzymatic method at pH 7.0 and pH 9.0 using UV-Vis spectrophotometer. Hypoglycemic activities of L. scariola were carried out in alloxan-induced male diabetic rats at both acute and subchronic exposure. RESULTS: The results showed a significant alteration in the lambdamax value of Ni (II) in combination with L. scariola leaves extracts at both pH 7.0 and 9.0. The aqueous extract also produced a significant reduction in the glucose concentration at pH 7.0 and pH 9.0 even in presence of Ni (II) in vitro. Lactuca scariola leaves in either acute or subchronic supplementation showed a greater glucose tolerance and hypoglycemic regulation of blood sugar in diabetic rats with or without nickel (II) treatments. CONCLUSIONS: Lactuca scariola leaves can be a substitute for synthetic drugs to treat diabetic patients. PMID- 26352091 TI - Williams-Beuren Syndrome: Experience of 43 Patients and a Report of an Atypical Case from a Tertiary Care Center in India. AB - Williams-Beuren syndrome (WBS) or Williams syndrome (OMIM 194050) is a multisystem disorder manifested by neurodevelopmental delay and is caused by a hemizygous deletion of ~ 1.5-1.8 Mb in the 7q11.23 region. Clinical features include cardiovascular anomalies (mainly supravalvular aortic stenosis), peripheral pulmonary stenosis, distinctive facies, intellectual disability (usually mild), unique personality characteristics, and growth and endocrine abnormalities. Clinical diagnostic criteria are available for WBS; however, the mainstay of diagnosis is the detection of the contiguous gene deletion. Although FISH remains the most widely used laboratory test, the diagnosis can also be established by means of qPCR, MLPA, microsatellite marker analysis, and chromosomal microarray (CMA). We evaluated the utility of MLPA to detect deletion/duplication in the 7q11.23 region in 43 patients suspected to have WBS using MLPA kits for microdeletion syndromes. A hemizygous deletion in the 7q11.23 region was found in 41 (95.3%) patients using MLPA. One patient had an atypical deletion detected by CMA. During the initial period of this study, the results of 12 patients tested by MLPA were also confirmed by FISH. Compared to FISH and CMA, MLPA is a cheaper, high-throughput, less labor-intensive and less time-consuming technique for the diagnosis of WBS. Although CMA is expensive and labor intensive, its effectiveness is demonstrated to detect an atypical deletion and to delineate the breakpoints. PMID- 26352092 TI - Estrogen Receptor Folding Modulates cSrc Kinase SH2 Interaction via a Helical Binding Mode. AB - The estrogen receptors (ERs) feature, next to their transcriptional role, important nongenomic signaling actions, with emerging clinical relevance. The Src Homology 2 (SH2) domain mediated interaction between cSrc kinase and ER plays a key role in this; however the molecular determinants of this interaction have not been elucidated. Here, we used phosphorylated ER peptide and semisynthetic protein constructs in a combined biochemical and structural study to, for the first time, provide a quantitative and structural characterization of the cSrc SH2-ER interaction. Fluorescence polarization experiments delineated the SH2 binding motif in the ER sequence. Chemical shift perturbation analysis by nuclear magnetic resonance (NMR) together with molecular dynamics (MD) simulations allowed us to put forward a 3D model of the ER-SH2 interaction. The structural basis of this protein-protein interaction has been compared with that of the high affinity SH2 binding sequence GpYEEI. The ER features a different binding mode from that of the "two-pronged plug two-hole socket" model in the so-called specificity determining region. This alternative binding mode is modulated via the folding of ER helix 12, a structural element directly C-terminal of the key phosphorylated tyrosine. The present findings provide novel molecular entries for understanding nongenomic ER signaling and targeting the corresponding disease states. PMID- 26352093 TI - Electrical stimulation of the amygdala modifies the negative feedback effect of glucocorticoids on the adrenocortical responses to stress. AB - OBJECTIVE: The amygdala (AMG) plays a facilitatory role in the hypothalamic pituitary-adrenal (HPA) axis. The effect of the AMG on the negative feedback exerted by glucocorticoids (GC) is not clear. We investigated the effect of repeated electrical stimulation of the AMG on the feedback action of GC upon the adrenocortical (AC) response to stressful stimuli. METHODS: Rats received electrical stimulation into the central amygdalar nucleus once daily for 4 days. At days 5 and 12 after the onset of stimulation, rats were treated with dexamethasone (Dex) or vehicle and were exposed to either photic or acoustic stress stimuli, and serum corticosterone (CS) was measured. In another group of rats, we measured the binding of Dex to the hippocampal cytosol at 5 and 12 days after the AMG stimulation. RESULTS: At 5 and 12 days after the onset of stimulation or a sham control, stress increased the serum CS level. In the sham group, Dex completely inhibited the CS response, but at 5 days after stimulation, it was significantly less effective in doing this. At day 12, Dex was as effective as in the control group. AMG stimulation delayed the return of CS response to basal levels and caused a significant decrease in the binding capacity of Dex to hippocampal cytosol. CONCLUSION: Electrical stimulation of the AMG caused a transient impairment of the feedback action of GC upon the stress response. This effect may be due to the decrease in hippocampal corticosteroid receptors. This suggests that the impaired GC feedback caused by AMG stimulation may be involved in the facilitatory effect of the AMG on the function of the AC axis. PMID- 26352094 TI - Quantitative evaluation of cellular uptake, DNA incorporation and adduct formation in cisplatin sensitive and resistant cell lines: Comparison of different Pt-containing drugs. AB - The use of Pt-containing compounds as chemotherapeutic agents facilitates drug monitoring by using highly sensitive elemental techniques like inductively coupled plasma mass spectrometry (ICP-MS). However, methodological problems arise when trying to compare different experiments due to the high variability of biological parameters. In this work we have attempted to identify and correct such variations in order to compare the biological behavior of cisplatin, oxaliplatin and pyrodach-2 (a novel platinum-containing agent). A detailed study to address differential cellular uptake has been conducted in three different cell lines: lung adenocarcinoma (A549); cisplatin-sensitive ovarian carcinoma (A2780); and cisplatin-resistant ovarian carcinoma (A2780cis). The normalization of Pt results to cell mass, after freeze-drying, has been used to minimize the errors associated with cell counting. Similarly, Pt accumulation in DNA has been evaluated by referencing the Pt results to the DNA concentration, as measured by (31)P monitoring using flow-injection and ICP-MS detection. These strategies have permitted to address significantly lower Pt levels in the resistant cells when treated with cisplatin or oxaliplatin as well as an independent behaviour from the cell type (sensitive or resistant) for pyrodach-2. Similarly, different levels of incorporation in DNA have been found for the three drugs depending on the cell model revealing a different behavior regarding cell cisplatin resistance. Further speciation experiments (by using complementary HPLC-ICP-MS and HPLC-ESI-Q-TOF MS) have shown that the main target in DNA is still the N7 of the guanine but with different kinetics of the ligand exchange mechanism for each of the compounds under evaluation. PMID- 26352095 TI - Rotational Analysis of Spherical, Optically Anisotropic Janus Particles by Dynamic Microscopy. AB - We analyze the rotational dynamics of spherical colloidal Janus particles made from silica (SiO2) with a hemispherical gold/palladium (Au/Pd) cap. Since the refractive index difference between the surrounding fluid and a two-faced, optically anisotropic Janus microsphere is a function of the particle's orientation, it is possible to observe its rotational dynamics with bright-field optical microscopy. We investigate rotational diffusion and constant rotation of single Janus microspheres which are partially tethered to a solid surface so they are free to rotate but show little or no translational motion. Also, since the metal cap is a powerful catalyst in the breakdown of hydrogen peroxide, H2O2, the particles can be activated chemically. In this case, we analyze the motion of coupled Janus dimers which undergo a stable rotary motion about a mutual center. The analysis of both experimental and simulation data, which are microscopy and computer-generated videos, respectively, is based upon individual particle tracking and differential dynamic microscopy (DDM). DDM, which typically requires ensemble averages to extract meaningful information for colloidal dynamics, can be effective in certain situations for systems consisting of single entities. In particular, when translational motion is suppressed, both rotational diffusion and constant rotation can be probed. PMID- 26352096 TI - Understanding the Impact of Obesity on Short-term Outcomes and In-hospital Costs After Instrumented Spinal Fusion. AB - BACKGROUND: Obesity rates continue to rise along with the number of obese patients undergoing elective spinal fusion. OBJECTIVE: To evaluate the impact of obesity on resource utilization and early complications in patients undergoing surgery for degenerative spine disease. METHODS: A single-institution retrospective analysis was conducted on patients with degenerative spine disease requiring instrumentation between 2008 and 2012. The 801 identified patients were grouped based on a body mass index (BMI) of <30 (nonobese, n = 478), >=30 and <40 (obese, n = 283), and alternatively BMIs of >=40 (morbidly obese, n = 40). Baseline characteristics, surgical outcomes and requirements, complications, and cost were compared. Logistic and linear regression analyses were used to determine the strength of association between obesity and outcomes for categorical and continuous data, respectively. RESULTS: Significant differences were found in comorbidities between cohorts. Multivariate analysis revealed significant associations between obesity and longer anesthesia times (30 minutes, P = .008), and surgical times (24 minutes, P = .02). Additionally, there was a 2.8 times higher rate of wound complications in obese patients (4.2% vs 1.5, P = .03), and 2.5 times higher rate of major medical complications (7.8% vs 3.1, P = .01). Morbid obesity resulted in a 10 times higher rate of wound complications (P < .001). Morbid obesity resulted in a $9078 (P = .005) increase in overall cost of care. CONCLUSION: Increased BMI is associated with longer operative times, increased complication rates, and increased cost independent of comorbidities. These effects are more pronounced with morbidly obese patients, further supporting a role for preoperative weight loss. PMID- 26352097 TI - Incidence and Risk Factors of Delayed Facial Palsy After Vestibular Schwannoma Resection. AB - BACKGROUND: Preservation of facial nerve function following vestibular schwannoma surgery is a high priority. Even those patients with normal to near-normal function in the early postoperative period remain at risk for delayed facial palsy (DFP). OBJECTIVE: To evaluate the incidence and prognosis of DFP and to identify risk factors for its occurrence. METHODS: A retrospective cohort study of 489 patients who underwent vestibular schwannoma resection at our institution between 2000 and 2014. Delayed facial palsy was defined as deterioration in facial function of at least 2 House-Brackmann (HB) grades between postoperative days 5 to 30. Only patients with a HB grade of I to III by postoperative day 5 were eligible for study inclusion. RESULTS: One hundred twenty-one patients with HB grade IV to VI facial weakness at postoperative day 5 were excluded from analysis. Of the remaining 368, 60 (16%) patients developed DFP (mean 12 days postoperatively, range: 5-25 days). All patients recovered function to HB grade I to II by a mean of 33 days (range: 7-86 days). Patients that developed DFP had higher rates of gross total resections (83% vs 71%, P = .05) and retrosigmoid approaches (72% vs 52%, P < .01). There was no difference in recovery time between patients who received treatment with steroids, steroids with antivirals, or no treatment at all (P = .530). CONCLUSION: Patients with a gross total tumor resection or undergoing a retrosigmoid approach may be at higher risk of DFP. The prognosis is favorable, with patients likely recovering to normal or near-normal facial function within 1 month of onset. PMID- 26352098 TI - Spinal Anaplastic Oligodendroglioma With Oligodendrogliomatosis: Molecular Markers and Management: Case Report. AB - BACKGROUND AND IMPORTANCE: Spinal cord oligodendrogliomas are rare tumors, with a reported incidence varying between 0.8% and 4.7% of all spinal cord tumors and just over 50 cases reported in the literature. Of these, only 9 cases are histologically defined as anaplastic oligodendrogliomas, with few having complete molecular characterization. The diffuse tumor spread that can occur along the subarachnoid space with secondary invasion of the leptomeninges is called oligodendrogliomatosis and is associated with poor outcome. CLINICAL PRESENTATION: A 68-year-old man with a history of lumbar stenosis status after lumbar decompression presented with new-onset right lower-extremity weakness. Magnetic resonance imaging demonstrated an intramedullary lesion from T9 to T12. During an attempted diagnostic biopsy, numerous intradural intramedullary lesions not present on magnetic resonance imaging were observed. Tissue biopsy demonstrated a 1p/19q-codeleted anaplastic oligodendroglioma with diffuse oligodendrogliomatosis. Postoperative treatment included 39.2-Gy radiation over 22 fractions from T1 to the bottom of the thecal sac with a boost to the T9-T12 area, the primary site of disease, to a total dose of 43.2 Gy in 24 fractions, followed by adjuvant temozolomide at a dose of 200 mg/m on days 1 to 5 in a 28 day cycle. At the 1-year follow-up, the patient demonstrated moderate neurological improvement. CONCLUSION: Management, prognosis, and use of molecular data in the decision-making algorithm for these patients are discussed, together with a review of all cases of primary intradural intramedullary spinal anaplastic oligodendrogliomas reported to date. Our study indicates that the combination of sequential treatment with radiation and temozolomide might provide a favorable outcome in the case of 1p/19q-codeleted spinal anaplastic oligodendrogliomas and that molecular analysis can be beneficial in guiding treatment strategies, although the impact of IDH mutations on these tumors is still unclear. PMID- 26352099 TI - Heterotopic Mucosal Grafting Enables the Delivery of Therapeutic Neuropeptides Across the Blood Brain Barrier. AB - BACKGROUND: The blood-brain barrier represents a fundamental limitation in treating neurological disease because it prevents all neuropeptides from reaching the central nervous system (CNS). Currently, there is no efficient method to permanently bypass the blood-brain barrier. OBJECTIVE: To test the feasibility of using nasal mucosal graft reconstruction of arachnoid defects to deliver glial derived neurotrophic factor (GDNF) for the treatment of Parkinson disease in a mouse model. METHODS: The Institutional Animal Care and Use Committee approved this study in an established murine 6-hydroxydopamine Parkinson disease model. A parietal craniotomy and arachnoid defect was repaired with a heterotopic donor mucosal graft. The therapeutic efficacy of GDNF (2 MUg/mL) delivered through the mucosal graft was compared with direct intrastriatal GDNF injection (2 MUg/mL) and saline control through the use of 2 behavioral assays (rotarod and apomorphine rotation). An immunohistological analysis was further used to compare the relative preservation of substantia nigra cell bodies between treatment groups. RESULTS: Transmucosal GDNF was equivalent to direct intrastriatal injection at preserving motor function at week 7 in both the rotarod and apomorphine rotation behavioral assays. Similarly, both transmucosal and intrastriatal GDNF demonstrated an equivalent ratio of preserved substantia nigra cell bodies (0.79 +/- 0.14 and 0.78 +/- 0.09, respectively, P = NS) compared with the contralateral control side, and both were significantly greater than saline control (0.53 +/- 0.21; P = .01 and P = .03, respectively). CONCLUSION: Transmucosal delivery of GDNF is equivalent to direct intrastriatal injection at ameliorating the behavioral and immunohistological features of Parkinson disease in a murine model. Mucosal grafting of arachnoid defects is a technique commonly used for endoscopic skull base reconstruction and may represent a novel method to permanently bypass the blood-brain barrier. PMID- 26352100 TI - Commentary: Cost Comparison of Surgical and Endovascular Treatment of Unruptured Giant Intracranial Aneurysms. PMID- 26352101 TI - Cytoprotective effects of ferritin on doxorubicin-induced breast cancer cell death. AB - Ferritin is a major iron storage protein and essential for iron homeostasis. It has a wide range of functions in the body including iron delivery, immunosuppression, angiogenesis, and cell proliferation. Ferritin is overexpressed in many cancer cells, but its precise role in cancer is unclear. In the present study, we examined the functional roles of ferritin in protecting the MCF-7 breast cancer cell line against treatment with the chemotherapeutic agent doxorubicin. The effects of ferritin (human liver ferritin) and doxorubicin on the human MCF-7 breast cancer cell line were evaluated using the cell viability assay. The impact of decreasing ferritin light chain (FTL) and ferritin heavy chain (FTH) expression on doxorubicin sensitivity was assessed using siRNA. Reactive oxygen species (ROS) was also measured using the fluorescence probe CM H2DCFDA. The mechanism of modulated chemosensitivity was evaluated by western blot analysis. Ferritin treatment activated MCF-7 cell proliferation in a concentration- and time-dependent manner. While treatment with doxorubicin alone significantly increased intracelullar ROS production, the addition of ferritin decreased this ROS formation, thereby reducing doxorubicin-induced MCF-7 cell death. The inhibition of FTL and FTH by siRNA sensitized cells to doxorubicin. Treatment with doxorubicin alone significantly induced the cell cycle-dependent kinase inhibitor protein p21, whereas ferritin reduced p21 expression. Thus, ferritin plays a critical role in protecting MCF-7 cells against the chemotherapeutic drug doxorubicin. A targeted reduction of ferritin may be a useful strategy for overcoming chemoresistance in breast cancer. PMID- 26352102 TI - Overgrowth after femoral shaft fractures in infants treated with a Pavlik harness. AB - This study was performed to determine whether overgrowth occurs when treating infantile femoral shaft fractures with a Pavlik harness. Twenty-three patients, aged less than 1 year, treated with a Pavlik harness for a femoral shaft fracture were included. Shortening at the time of injury was recorded on radiographs and compared with those obtained at the follow-up visit 18 months or later. Average overgrowth was 5 mm (1-18 mm). Overgrowth occurs in infants following treatment of femoral fractures with a Pavlik harness. Initial shortening of up to 18 mm was acceptable and resulted in a leg-length discrepancy of less than 5 mm due to overgrowth in our population. PMID- 26352103 TI - Buried versus unburied Kirschner wires in the management of paediatric lateral condyle elbow fractures: a comparative study from a tertiary centre. AB - There is little consensus on whether Kirschner wire (K-wire) burial is preferable in the management of paediatric lateral humeral condyle fractures. We identified 124 patients from May 2008 to August 2014. Sixty received buried K-wires and 64 received unburied wires. We found no significant difference in the infection rates between groups, but a high rate of skin erosion (23%) in the buried group, with a subsequent high rate of infection in this subgroup (40%). We found a strong association of wire erosion following early surgery. There is a considerable cost saving associated with using unburied wires. We therefore recommend the routine use of unburied wires. PMID- 26352104 TI - Comparison of open reduction alone and open reduction plus Dega osteotomy in developmental dysplasia of the hip. AB - In the treatment of developmental dysplasia of the hip, concentric reduction of the femoral head into the acetabular cavity plays a key role in the natural development of the acetabulum. However, there is still debate on the need for additional acetabular osteotomies and their timing. In this study, we compared open reduction (OR) alone with OR plus Dega osteotomy for acetabular index (AI) development. Twenty patients, 10 in each group, who underwent either OR alone or OR plus Dega osteotomy were studied retrospectively. All patients were diagnosed with developmental dysplasia of the hip and none of them received treatment previously. Preoperative, early postoperative, and follow-up radiographs were gathered, radiological grading was performed according to Tonnis, and AI angles were measured. The OR group had a mean age of 24.5 months, whereas the Dega group had a mean age of 24.8 months. The mean follow-up period of the OR group and Dega group was 57.8 and 66.6 months, respectively. In the OR group, the initial mean AI was 37.5 degrees whereas in the Dega group it was 46 degrees . After the follow-up, despite the acetabular development in the OR group being twice as fast, the final mean AI was 25.5, whereas it was 15.9 in the Dega group. The difference was statistically significant (P<0.05). Using Tonnis' definition, the Dega group ended up with 70% normal hips, 20% mild dysplasia, and 10% severe dysplasia, whereas the OR group had 20% normal hips, 30% mild dysplasia, and 50% severe dysplasia at the final visit. There was no correlation between the initial radiological grading of dislocation and the final result. OR plus Dega osteotomy is a good option to regain acetabular coverage over the femoral head. It provides better radiographic results after a 5-year follow-up period in patients with a mean age of 25 months. OR alone should not be performed unless the child had mildly dysplastic acetabulum according to Tonnis' definition. PMID- 26352105 TI - Venom and Dufour's glands of the emerald cockroach wasp Ampulex compressa (Insecta, Hymenoptera, Sphecidae): structural and biochemical aspects. AB - The digger wasp species Ampulex compressa produces its venom in two branched gland tubules. They terminate in a short common duct, which is bifurcated at its proximal end. One leg is linked with the venom reservoir, the other one extends to the ductus venatus. Each venom gland tubule possesses, over its entire length, a cuticle-lined central duct. Around this duct densely packed class 3 gland units each composed of a secretory cell and a canal cell are arranged. The position of their nuclei was demonstrated by DAPI staining. The brush border of the secretory cells surrounds the coiled end-apparatus. Venom is stored in a bladder like reservoir, which is surrounded by a thin reticulated layer of muscle fibres. The reservoir as a whole is lined with class 3 gland units. The tubiform Dufour's gland has a length of about 350 MUm (? 125 MUm) only and is surrounded by a network of pronounced striated muscle fibres. The glandular epithelium is mono layered belonging to the class 1 type of insect epidermal glands. The gland cells are characterized by conspicuous lipid vesicles. Secretion of material via the gland cuticle into the gland lumen is apparent. Analysis of the polypeptide composition demonstrated that the free gland tubules and the venom reservoir contain numerous proteins ranging from 3.4 to 200 kDa. The polypeptide composition of the Dufour's gland is completely different and contains no lectin binding glycoproteins, whereas a dominant component of the venom droplets is a glycoprotein of about 80 kDa. Comparison of the venom reservoir contents with the polypeptide pattern of venom droplets revealed that all of the major proteinaceous constituents are secreted. The secreted venom contains exclusively proteins present in the soluble contents of the venom gland. The most abundant compound class in the Dufour's gland consisted of n-alkanes followed by monomethyl-branched alkanes and alkadienes. Heptacosane was the most abundant n alkane. Furthermore, a single volatile compound, 2-methylpentan-3-one, was identified in various concentrations in the lipid extract of the Dufour's gland. PMID- 26352106 TI - The Long-term Efficacy and Safety of Fecal Microbiota Transplant for Recurrent, Severe, and Complicated Clostridium difficile Infection in 146 Elderly Individuals. AB - OBJECTIVES: Clostridium difficile infection (CDI) in the elderly has a higher prevalence, greater morbidity and mortality, and lower response to conventional treatment than the general population. Fecal microbiota transplant (FMT) is highly effective therapy for CDI but has not been studied specifically in the elderly. This study aims to determine the long-term efficacy and safety of FMT for recurrent (RCDI), severe (SCDI), and complicated (CCDI) CDI in elderly patients. METHODS: A multicenter, long-term follow-up study was performed with demographic, pre-FMT, and post-FMT data collected from elderly patients with RCDI, SCDI, and CCDI, through a 47-item questionnaire. Outcome measures included primary and secondary cure rates, early (<12 wk) and late (>=12 wk) recurrence rates, and adverse events (AEs), including post-FMT diagnoses. RESULTS: Of 168 eligible patients, 146 patients met the inclusion criteria. Of these, 68.5% were women. The mean (range) age was 78.6 (65 to 97) years and the follow-up period was 12.3 (1 to 48) months. FMT was performed for RCDI in 89 (61%), SCDI in 45 (30.8%), and CCDI in 12 (8.2%) patients. The primary and secondary cure rates were 82.9% and 95.9%, respectively. Early and late recurrences occurred in 25 and 6 patients, respectively. AEs included CDI-negative diarrhea in 7 (4.8%) and constipation in 4 (2.7%) patients. Serious AEs, recorded in 6 patients, were hospital admissions for CDI-related diarrhea, one of which culminated in death. New diagnoses post-FMT included microscopic colitis (2), Sjogren syndrome (1), follicular lymphoma (1), contact dermatitis and idiopathic Bence-Jones proteinuria (1), and laryngeal carcinoma (1)-all, however, were associated with predisposing factors. CONCLUSIONS: FMT is a safe and effective treatment option for RCDI, SCDI, and CCDI in elderly patients. PMID- 26352107 TI - Hepatocellular Carcinoma Surveillance Among Cirrhotic Patients With Commercial Health Insurance. AB - GOALS: To evaluate hepatocellular carcinoma (HCC) surveillance rates among commercially insured patients, and evaluate factors associated with compliance with surveillance recommendations. BACKGROUND: Most HCC occurs in patients with cirrhosis. American Association for the Study of Liver Diseases and European Association for the Study of the Liver guidelines each recommend biannual HCC surveillance for cirrhotic patients to diagnose HCC at an early, curable stage. However, compliance with these guidelines in commercially insured patients is unknown. STUDY: We used the Truven Health Analytics databases from 2006 to 2010, using January 1, 2006 as the anchor date for evaluating outcomes. The primary outcome was continuous surveillance measure, defined as the proportion of time "up-to-date" with surveillance (PTUDS), with the 6-month interval immediately following each ultrasound categorized as "up-to-date." RESULTS: During a median follow-up of 22.9 (interquartile range, 16.3 to 33.9) months among 8916 cirrhotic patients, the mean PTUDS was 0.34 (SD, 0.29), and the median was 0.31 (interquartile range, 0.03 to 0.52). These values increased only modestly with inclusion of serum alpha-fetoprotein testing, contrast-enhanced abdominal computed tomographic scans or magnetic resonance imagings, and/or extension of up to-date time to 12 months. Being diagnosed by a nongastroenterology provider and increasing age were significantly associated with decreased HCC surveillance (P<0.05), whereas a history of a hepatic decompensation event, presence of any component of the metabolic syndrome, and diagnosis of hepatitis B or hepatitis C were significantly associated with increased surveillance (P<0.05). However, even among patients with the most favorable characteristics, surveillance rates remained low. CONCLUSIONS: HCC surveillance rates in commercially insured at-risk patients remain poor despite formalized guidelines, highlighting the need to develop interventions to improve surveillance rates. PMID- 26352108 TI - Mechanism of Copper(I)-Catalyzed 5-Iodo-1,2,3-triazole Formation from Azide and Terminal Alkyne. AB - 5-Iodo-1,2,3-triazole (iodotriazole) can be prepared from a copper(I)-catalyzed reaction between azide and terminal alkyne in the presence of an iodinating agent, with 5-protio-1,2,3-triazole (protiotriazole) as the side product. The increasing utilities of iodotriazoles in synthetic and supramolecular chemistry drive the efforts in improving their selective syntheses based on a sound mechanistic understanding. A routinely proposed mechanism takes the cue from the copper(I)-catalyzed azide-alkyne cycloaddition, which includes copper(I) acetylide and triazolide as the early and the late intermediates, respectively. Instead of being protonated to afford protiotriazole, an iodinating agent presumably intercepts the copper(I) triazolide to give iodotriazole. The current work shows that copper(I) triazolide can be iodinated to afford iodotriazoles. However, when the reaction starts from a terminal alkyne as under the practical circumstances, 1-iodoalkyne (iodoalkyne) is an intermediate while copper(I) triazolide is bypassed on the reaction coordinate. The production of protiotriazole commences after almost all of the iodoalkyne is consumed. Using (1)H NMR to follow a homogeneous iodotriazole forming reaction, the rapid formation of an iodoalkyne is shown to dictate the selectivity of an iodotriazole over a protiotriazole. To ensure the exclusive production of iodotriazole, the complete conversion of an alkyne to an iodoalkyne has to, and can be, achieved at the early stage of the reaction. PMID- 26352109 TI - Hospital autopsy audit: discordant primary clinical diagnoses are found in 20% of cases in a reducing autopsy case load. Selection bias or significant findings? PMID- 26352110 TI - KRAS, NRAS, BRAF mutations and high counts of poorly differentiated clusters of neoplastic cells in colorectal cancer: observational analysis of 175 cases. AB - A novel grading system based on the counting of poorly differentiated clusters (PDC) of neoplastic cells at the invasive margin and in the tumour stroma was recently introduced among the histological parameters predictive of adverse clinical outcome in colorectal cancer (CRC). The aim of this study was to correlate the histological grade based on PDC and the mutational status of KRAS, NRAS and BRAF genes in 175 consecutive CRCs. The highest PDC count under the objective lens of a *20 microscopic field in each tumour was considered for grading assessment, so that PDC counts <5, 5-9 and >=10 PDCs were defined grade 1, grade 2 and grade 3, respectively. Hotspots mutations were identified using the MassArray platform. Overall, there were 42 (24%) mutated tumours. Mutational status was significantly associated with high pT stage (p = 0.0021), advanced pTNM stage (p = 0.0018), nodal metastases (p = 0.006), tumour budding (p = 0.022) and high PDC grade (p = 0.0022). KRAS mutations were significantly associated with PDC grade (p = 0.0379), while BRAF mutations were associated with PDC-G3 although statistical significance was not reached. No significant associations were found between NRAS and PDC. The significant association between mutated KRAS and PDC grade suggests that KRAS mutations may be involved in the formation of PDC. PMID- 26352111 TI - Comparison of the Freelite serum free light chain (SFLC) assay with serum and urine electrophoresis/immunofixation and the N Latex FLC assay. AB - Few reports have compared available serum free light chain (SFLC) assays. Here, a retrospective audit of the Freelite SFLC assay compared results to electrophoresis (EP)/immunofixation (IFX) and the N Latex FLC assay.A total of 244 samples collected over 3.5 months were studied using the Freelite and N Latex FLC nephelometry assays. Results were compared with serum and/or urine EP/IFX. The precision and linearity of the N Latex FLC assay was examined.Detectable paraprotein by serum or urine EP/IFX was present in 94% of samples with kappa and 100% with lambda FLC restriction. The correlation between the assays was higher for kappa (rho = 0.97) than lambda (rho = 0.89) especially when lambda results were above the upper limit of normal (rho = 0.62). Agreement in the categorical diagnosis as measured by the Cohen's kappa statistic was good (0.70). The N Latex FLC assay displayed good precision and linearity. In discordant samples the Freelite and N Latex FLC assays had equivalent agreement with IFX.Traditional methods of EP/IFX detected paraproteins in the majority of cases. Correlation between the Freelite and N Latex FLC assay is better for kappa than lambda FLC. The two assays are not entirely equivalent. Care should be taken by interpreting physicians and laboratories considering switching assays. PMID- 26352112 TI - Congenital late onset thrombotic thrombocytopenic purpura: a diagnostic challenge. PMID- 26352113 TI - Malignant peripheral nerve sheath tumour arising de novo from ganglioneuroma. PMID- 26352114 TI - Preferential occurrence of RHOA mutation in gastric and colorectal cancers. PMID- 26352115 TI - Spiral bodies in pulse granulomas are remnant plant vascular structures. PMID- 26352116 TI - Hospital Incidence and Outcomes of the Acute Respiratory Distress Syndrome Using the Kigali Modification of the Berlin Definition. AB - RATIONALE: Estimates of the incidence of the acute respiratory distress syndrome (ARDS) in high- and middle-income countries vary from 10.1 to 86.2 per 100,000 person-years in the general population. The epidemiology of ARDS has not been reported for a low-income country at the level of the population, hospital, or intensive care unit (ICU). The Berlin definition may not allow identification of ARDS in resource-constrained settings. OBJECTIVES: To estimate the incidence and outcomes of ARDS at a Rwandan referral hospital using the Kigali modification of the Berlin definition: without requirement for positive end-expiratory pressure, hypoxia cutoff of SpO2/FiO2 less than or equal to 315, and bilateral opacities on lung ultrasound or chest radiograph. METHODS: We screened every adult patient for hypoxia at a public referral hospital in Rwanda for 6 weeks. For every patient with hypoxia, we collected data on demographics and ARDS risk factors, performed lung ultrasonography, and evaluated chest radiography when available. MEASUREMENTS AND MAIN RESULTS: Forty-two (4.0%) of 1,046 hospital admissions met criteria for ARDS. Using various prespecified cutoffs for the SpO2/FiO2 ratio resulted in almost identical hospital incidence values. Median age for patients with ARDS was 37 years, and infection was the most common risk factor (44.1%). Only 30.9% of patients with ARDS were admitted to an ICU, and hospital mortality was 50.0%. Using traditional Berlin criteria, no patients would have met criteria for ARDS. CONCLUSIONS: ARDS seems to be a common and fatal syndrome in a hospital in Rwanda, with few patients admitted to an ICU. The Berlin definition is likely to underestimate the impact of ARDS in low-income countries, where resources to meet the definition requirements are lacking. Although the Kigali modification requires validation before widespread use, we hope this study stimulates further work in refining an ARDS definition that can be consistently used in all settings. PMID- 26352117 TI - No Effect of Different Stimulation Conditions on Verbal Fluency and Visuospatial Orientation in Patients with Subthalamic Nucleus Deep Brain Stimulation. AB - BACKGROUND: Subthalamic nucleus deep brain stimulation is an effective treatment for the symptomatic treatment of Parkinson's disease. Apart from the obvious motor benefits, some cognitive side effects have been reported, particularly in verbal fluency. OBJECTIVES: Our aim was to evaluate the effects of the stimulation on verbal fluency and visuospatial orientation with changing stimulation conditions in 35 patients with Parkinson's disease. METHODS: Patients were randomized for their stimulation conditions as 'both on', 'both off', 'right on', and 'left on' and underwent verbal fluency and visuospatial orientation tasks during their drug-on periods. Letter and categorical fluency tasks and Benton's Judgment of Line Orientation Test were used for assessment. RESULTS: Overall, 6 patients were excluded due to dementia or depression. For verbal fluency, the number of words they produced in 1 min was similar in four stimulation conditions (p > 0.05). No significant difference was found between stimulation conditions in the spatial orientation task. CONCLUSIONS: We were unable to find any significant changes in verbal fluency and visuospatial orientation task scores with different stimulation conditions. This result suggests that either stimulation has no effect on given domains or the effect is so small that more detailed batteries are required to detect the difference. PMID- 26352120 TI - Retrospective Evaluation on the Analgesic Activities of 2 Compounded Topical Creams and Voltaren Gel in Chronic Noncancer Pain. AB - Pharmacologic treatment of chronic pain is challenging. Oral therapy may require multiple medications; each has side effects, dose limitations, and limited efficacy. Compounded topical formulations have evolved as potential treatment options. The objective of this study was to evaluate the efficacy of 2 compounded topical creams, "Cream I" and "Cream II," in patients with chronic extremity, joint, musculoskeletal, neuropathic, or other chronic topical pain conditions and compare their efficacy with Voltaren gel. The primary efficacy outcome was the change in visual numeric pain intensity score from pretreatment to posttreatment. The Cream I contained Flurbiprofen (20%), Tramadol (5%), Clonidine (0.2%), Cyclobenzaprine (4%), and Bupivacaine (3%). The Cream II contained Flurbiprofen (20%), Baclofen (2%), Clonidine (0.2%), Gabapentin (10%), and Lidocaine (5%). The Voltaren gel contained 1% diclofenac sodium. A total of 2177 patients were evaluated, 826 males and 1351 females. During their medical treatment, 1141 patients received Cream I, 527 patients received Cream II, and 509 patients received Voltaren gel. After treatment, the pain intensity score decreased by 3.11 +/- 1.65 (37%) with Cream I (from 8.44 +/- 1.19 to 5.33 +/- 2.0, P < 0.001), by 2.93 +/- 1.58 (35%) with Cream II (from 8.42 +/- 1.27 to 5.50 +/- 1.96, P < 0.001), and by 1.49 +/- 0.73 (19%) with Voltaren gel (from 7.93 +/- 0.81 to 6.44 +/- 1.14, P < 0.001). Cream I and Cream II did not differ significantly in efficacy, and both were significantly more effective than Voltaren gel (P < 0.001). It is concluded that Voltaren gel had less efficacy than the compounded creams, which were effective and provided pain relief in the majority of the patients studied. PMID- 26352123 TI - Pellagra's Three Ds: Dermatology, Death, and Dracula. PMID- 26352124 TI - Of Steinbeck and Sunburn. PMID- 26352125 TI - 19th Century Dermatologic Atlases in the Early Age of Photography. PMID- 26352126 TI - The Snark and the Skin: Jack London's Pacific Voyage. PMID- 26352127 TI - The 2-Step Method and the Recognition Process in Dermoscopy. PMID- 26352128 TI - Incorrect Information in Figure. PMID- 26352129 TI - JAMA DERMATOLOGY PATIENT PAGE. Venous Ulcers. PMID- 26352130 TI - AST/ALT ratio is not useful in predicting the degree of fibrosis in chronic viral hepatitis patients. AB - BACKGROUND AND AIM: Noninvasive tests are primarily used for staging hepatic fibrosis in patients with chronic liver disease. In clinical practice, serum aminotransferase levels, coagulation parameters, and platelet count have been used to predict whether or not a patient has cirrhosis. In addition, several studies have evaluated the accuracy of combinations (or ratios) of these measures. The present study aimed to investigate the relationship between five noninvasive models [AST/ALT ratio (AAR), aspartate aminotransferase to platelet ratio index (APRI), Bonacini cirrhosis discriminant score (CDS), age-platelet index (APind), and King's score] and the degree of hepatic fibrosis as determined by biopsy in patients with chronic hepatitis B and C. PATIENTS AND METHODS: A total of 380 patients with viral hepatitis (237 with chronic hepatitis B and 143 with chronic hepatitis C) who were seen at our clinic between January 2005 and January 2011 were retrospectively analyzed. The degree of fibrosis was determined using the Ishak score. Patients with a fibrosis score of 0-2 were considered to have low fibrosis and those with a score between 3 and 6 were considered to have high fibrosis. Five noninvasive models were compared between the groups with low and high fibrosis. RESULTS: There were statistically significant differences between the hepatitis B and C patients with high and low fibrosis with respect to APind (4.49+/-2.35 vs. 2.41+/-1.84; P<0.001 in hepatitis B and 4.83+/-2.25 vs. 2.92+/-1.88; P<0.001 in hepatitis C), APRI (1.00+/-1.17 vs. 0.47+/-0.39; P<0.001 in hepatitis B and 1.01+/-1.01 vs. 0.41+/-0.29; P<0.001 in hepatitis C), CDS (4.53+/-1.90 vs. 3.58+/-1.30; P<0.001 in hepatitis B and 4.71+/-2.03 vs. 3.42+/ 1.49; P<0.05 in hepatitis C), and King's score (24.31+/-3.14 vs. 7.65+/-6.70; P<0.001 in hepatitis B and 24.82+/-2.55 vs. 8.33+/-7.29; P<0.001 in hepatitis C). There were no significant differences in the AAR between the hepatitis B and C patients with high and low fibrosis (0.78+/-0.31 vs. 0.74+/-0.34; P=0.082 in hepatitis B and 0.91+/-0.40 vs. 0.85+/-0.27; P=0.25 in hepatitis C). The area under the receiver-operating characteristic curve of the APind, APRI, CDS, and King's score in the hepatitis B group were 0.767, 0.710, 0.646, and 0.770, respectively; these values were 0.732, 0.763, 0.677, and 0.783, respectively, in the hepatitis C group. CONCLUSION: In conclusion, our data suggest that four of the five noninvasive methods evaluated in this study can be used to predict advanced fibrosis in patients with hepatitis B and C. However, there was no significant relationship between the degree of hepatic fibrosis and the AAR score, indicating that AAR is not useful in estimating the fibrosis stage in hepatitis B and C patients. PMID- 26352131 TI - The role of upper gastrointestinal endoscopy in the era of modern antiretroviral therapy. AB - OBJECTIVE: Gastrointestinal disorders are common in HIV-positive patients and, in some cases, may be related to antiretroviral therapy (ART), making it difficult to determine the need for upper gastrointestinal (UGI) endoscopy. The primary aim of this study was to determine whether lymphocyte T CD4 cell counts were correlated with indications for endoscopy in these patients and with endoscopic diagnosis. PATIENTS AND METHODS: We prospectively collected data from consecutive HIV-positive patients undergoing UGI endoscopy between 2007 and 2013, and included 265 patients who had been receiving ART for at least 6 months. Parameters studied were demographics, immune parameters, comorbidities, comedications, indications for endoscopy, and endoscopic, pathologic, and microbiologic findings. RESULTS: The most frequent indications for UGI endoscopy were gastroesophageal reflux, epigastric pain, and other. Peptic esophagitis, esophageal candidiasis, and normal endoscopy were the most common diagnoses. The prevalence rates of Helicobacter pylori infection and neoplasia were 26.4 and 1.8%, respectively. Patients with CD4+ counts 200 cells/MUl or more had significantly lower rates of macrolide and nonmacrolide use, fewer comorbidities, and were less likely to have AIDS than patients with lower counts. They were also more likely to have normal UGI endoscopy and had a higher frequency of H. pylori infection. AIDS status and the presence of comorbidities were independent predictors of endoscopic abnormalities. CONCLUSION: UGI endoscopy remains a key diagnostic procedure for HIV-positive patients with UGI symptoms. AIDS and comorbidities are risk factors for the presence of mucosal lesions among HIV positive patients on ART. PMID- 26352132 TI - Risk stratification and detection of new colorectal neoplasms after colorectal cancer screening with faecal occult blood test: experiences from a Danish screening cohort. AB - BACKGROUND: Limited data exist on adenoma surveillance as recommended in the European guidelines for quality assurance in colorectal cancer (CRC) screening and diagnosis after faecal occult blood test (FOBT) screening. OBJECTIVE: To assess the European guidelines for adenoma surveillance after CRC screening with FOBT. MATERIALS AND METHODS: This was a population-based cohort-study of 176 782 Danish individuals aged 50-74 years invited for CRC screening in 2005-2006. Adenoma patients were stratified into risk groups (low A, medium B, high C) in accordance with the European guidelines and followed up for recurrence of new neoplasms until the end of 2011. Risk ratios (RR) between the risk groups were calculated to assess differences in the recurrence rates of neoplasms. RESULTS: Among 84 803 screening participants, 2059 had positive FOBT, of whom 1861 underwent colonoscopy, and 709 patients had screen-detected adenomas. During a median follow-up period of 72.7 months, detection of new advanced adenomas (B+C) was significantly higher in risk group C than group A (RR 2.25, 95% confidence interval: 1.13-4.48). Nine patients were diagnosed with CRC: one in risk group A, two in B and six in C. The detection rate of CRC was higher in risk group C than A (RR 5.20, 95% confidence interval: 0.63-42.58), but not statistically significant. In risk group C, half of new advanced adenomas were detected within the first year and four of nine CRC were detected within 3 years. CONCLUSION: Risk stratification of adenoma patients, as recommended by the European guidelines, is appropriate for postpolypectomy surveillance after FOBT screening. PMID- 26352133 TI - Charged solvatochromic dyes as signal transducers in pH independent fluorescent and colorimetric ion selective nanosensors. AB - Ionophore-based ion selective optical nanosensors that operate independently of the sample pH are developed here by the use of electrically charged solvatochromic dyes as signal transducers. A series of dye molecules with a D-pi A structure was synthesized and characterized in various solvents and incorporated into ion selective nanospheres for K(+), Na(+), and H(+). Since dye leakage was greatly suppressed when the solvatochromic dyes were encapsulated in the nanosphere core, ion sensing nanospheres were explored for cellular ion imaging in Dictyostelium discoideum live cells but spontaneous dye loss resulted in undesired staining of cells. The in vitro analysis of potassium in human plasma was successfully demonstrated with this approach. A theoretical model was developed for the response of the ion selective nanosensors containing charged solvatochromic dyes. The nanosensors exhibited a tunable response range, high sensitivity, and good stability. PMID- 26352134 TI - Negative Finding From Computed Tomography of the Abdomen After Blunt Trauma. PMID- 26352135 TI - Eruptive Keratoacanthomas Associated With Leflunomide. PMID- 26352136 TI - Five-Year Follow-Up Study of Transurethral Plasmakinetic Resection of the Prostate for Benign Prostatic Hyperplasia. AB - PURPOSE: To explore the long-term clinical efficacy and safety of transurethral plasmakinetic resection of the prostate (PKRP) for benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: A total of 550 patients with BPH who had undergone PKRP from October 2006 to September 2009 were enrolled in this study. All patients were evaluated at baseline and follow-up (3, 12, 24, 36, 48, 60 months postoperatively) by peak flow rate (Qmax), postvoid residual (PVR), quality of life (QoL), International Prostate Symptom Score (IPSS), and Overactive Bladder Symptom Score (OABSS). Operative details and postoperative complications regarded as safety outcomes were documented. RESULTS: A total of 467 patients completed the 5-year follow-up. The mean duration of surgery was 36.43 minutes, mean catheterization time was 48.81 hours, mean hospital stay was 4.21 days. At 60 months postoperatively, the mean Qmax increased from 6.94 mL/s at baseline to 19.28 mL/s, the mean PVR decreased from 126.33 mL to 10.45 mL, the mean IPSS score decreased from 15.79 to 7.51, the mean QoL score decreased from 4.36 to 1.91, and the mean OABSS score decreased from 6.39 to 3.65 (P < 0.001), respectively. In perioperative complications, the blood transfusion rate was 2.7%, urinary tract infection rate was 3.6%; no transurethral resection syndrome (TUR syndrome) occurred. In late complications, urethral stricture rate was 5.4%, recurrent bladder outlet obstruction rate was 2.1%, and the reoperation rate was 4.5%. CONCLUSIONS: PKRP is based on conventional monopolar transurethral resection of the prostate (TURP) and uses a bipolar plasmakinetic system. Our results indicate that the long-term clinical efficacy and safety of PKRP for BPH are remarkable. In particular, the incidence of urethral stricture, recurrent bladder outlet obstruction, and reoperation is low. We suggest that PKRP is a reliable minimally invasive technique that may be the preferred procedure for the treatment of patients with BPH. PMID- 26352138 TI - Poisson-Gaussian Noise Reduction Using the Hidden Markov Model in Contourlet Domain for Fluorescence Microscopy Images. AB - In certain image acquisitions processes, like in fluorescence microscopy or astronomy, only a limited number of photons can be collected due to various physical constraints. The resulting images suffer from signal dependent noise, which can be modeled as a Poisson distribution, and a low signal-to-noise ratio. However, the majority of research on noise reduction algorithms focuses on signal independent Gaussian noise. In this paper, we model noise as a combination of Poisson and Gaussian probability distributions to construct a more accurate model and adopt the contourlet transform which provides a sparse representation of the directional components in images. We also apply hidden Markov models with a framework that neatly describes the spatial and interscale dependencies which are the properties of transformation coefficients of natural images. In this paper, an effective denoising algorithm for Poisson-Gaussian noise is proposed using the contourlet transform, hidden Markov models and noise estimation in the transform domain. We supplement the algorithm by cycle spinning and Wiener filtering for further improvements. We finally show experimental results with simulations and fluorescence microscopy images which demonstrate the improved performance of the proposed approach. PMID- 26352137 TI - Whole-Chain Tick Saliva Proteins Presented on Hepatitis B Virus Capsid-Like Particles Induce High-Titered Antibodies with Neutralizing Potential. AB - Ticks are vectors for various, including pathogenic, microbes. Tick saliva contains multiple anti-host defense factors that enable ticks their bloodmeals yet also facilitate microbe transmission. Lyme disease-causing borreliae profit specifically from the broadly conserved tick histamine release factor (tHRF), and from cysteine-rich glycoproteins represented by Salp15 from Ixodes scapularis and Iric-1 from Ixodes ricinus ticks which they recruit to their outer surface protein C (OspC). Hence these tick proteins are attractive targets for anti-tick vaccines that simultaneously impair borrelia transmission. Main obstacles are the tick proteins' immunosuppressive activities, and for Salp15 orthologs, the lack of efficient recombinant expression systems. Here, we exploited the immune enhancing properties of hepatitis B virus core protein (HBc) derived capsid-like particles (CLPs) to generate, in E. coli, nanoparticulate vaccines presenting tHRF and, as surrogates for the barely soluble wild-type proteins, cysteine-free Salp15 and Iric-1 variants. The latter CLPs were exclusively accessible in the less sterically constrained SplitCore system. Mice immunized with tHRF CLPs mounted a strong anti-tHRF antibody response. CLPs presenting cysteine-free Salp15 and Iric-1 induced antibodies to wild-type, including glycosylated, Salp15 and Iric-1. The broadly distributed epitopes included the OspC interaction sites. In vitro, the anti-Salp15 antibodies interfered with OspC binding and enhanced human complement-mediated killing of Salp15 decorated borreliae. A mixture of all three CLPs induced high titered antibodies against all three targets, suggesting the feasibility of combination vaccines. These data warrant in vivo validation of the new candidate vaccines' protective potential against tick infestation and Borrelia transmission. PMID- 26352139 TI - KML001 Induces Apoptosis and Autophagic Cell Death in Prostate Cancer Cells via Oxidative Stress Pathway. AB - We investigated the effects of KML001 (NaAsO2, sodium metaarsenite, Kominox), an orally bioavailable arsenic compound, on the growth and death of human prostate cancer cells and its mechanism of action. Growth inhibition was assessed by cytotoxicity assays in the presence or absence of inhibitor of apoptosis, inhibitor of autophagy or antioxidant N-Acetyl-L-cysteine to study mechanism of cell death induced by KML001 in PC3, DU145 and LNCaP prostate cancer cell lines. Electron microscopy, flow cytometry and Western blotting were used to study apoptotic and autophagic mechanisms. The DU145 xenograft model was used to determine the efficacy of KML001 in vivo. KML001 decreased the viability of cells and increased the percentage of annexin V-positive cells dose-dependently in prostate cancer cells, and LNCaP cells were more sensitive to KML001 than PC3 or DU145 cells. Electron microscopy revealed typical apoptotic characters and autophagic vacuoles in cells treated with KML001. Exposure to KML001 in prostate cancer cells induced apoptosis and autophagy in a time- and dose-dependent manner. KML001 induced dose-dependent accumulation of reactive oxygen species, and scavenging the reactive oxygen species with N-Acetyl-L-cysteine reduced LC3 and cleaved poly (ADP-ribose) polymerase. KML001 significantly inhibited tumor growth in the DU145 xenograft model. In addition, significant decrease of proliferation and significant increases of apoptosis and autophagy were observed in KML001-treated tumors than in vehicle-treated tumors. Exposure of human prostate cancer cells to KML001 induced both apoptosis and autophagic cell death via oxidative stress pathway. And KML001 had an antiproliferative effect on DU145 cells in xenograft mice. PMID- 26352140 TI - Correction: Postnatal Environmental Tobacco Smoke Exposure Related to Behavioral Problems in Children. AB - [This corrects the article DOI: 10.1371/journal.pone.0133604.]. PMID- 26352141 TI - The Maternal Maverick/GDF15-like TGF-beta Ligand Panda Directs Dorsal-Ventral Axis Formation by Restricting Nodal Expression in the Sea Urchin Embryo. AB - Specification of the dorsal-ventral axis in the highly regulative sea urchin embryo critically relies on the zygotic expression of nodal, but whether maternal factors provide the initial spatial cue to orient this axis is not known. Although redox gradients have been proposed to entrain the dorsal-ventral axis by acting upstream of nodal, manipulating the activity of redox gradients only has modest consequences, suggesting that other factors are responsible for orienting nodal expression and defining the dorsal-ventral axis. Here we uncover the function of Panda, a maternally provided transforming growth factor beta (TGF beta) ligand that requires the activin receptor-like kinases (Alk) Alk3/6 and Alk1/2 receptors to break the radial symmetry of the embryo and orient the dorsal ventral axis by restricting nodal expression. We found that the double inhibition of the bone morphogenetic protein (BMP) type I receptors Alk3/6 and Alk1/2 causes a phenotype dramatically more severe than the BMP2/4 loss-of-function phenotype, leading to extreme ventralization of the embryo through massive ectopic expression of nodal, suggesting that an unidentified signal acting through BMP type I receptors cooperates with BMP2/4 to restrict nodal expression. We identified this ligand as the product of maternal Panda mRNA. Double inactivation of panda and bmp2/4 led to extreme ventralization, mimicking the phenotype caused by inactivation of the two BMP receptors. Inhibition of maternal panda mRNA translation disrupted the early spatial restriction of nodal, leading to persistent massive ectopic expression of nodal on the dorsal side despite the presence of Lefty. Phylogenetic analysis indicates that Panda is not a prototypical BMP ligand but a member of a subfamily of TGF-beta distantly related to Inhibins, Lefty, and TGF-beta that includes Maverick from Drosophila and GDF15 from vertebrates. Indeed, overexpression of Panda does not appear to directly or strongly activate phosphoSmad1/5/8 signaling, suggesting that although this TGF beta may require Alk1/2 and/or Alk3/6 to antagonize nodal expression, it may do so by sequestering a factor essential for Nodal signaling, by activating a non Smad pathway downstream of the type I receptors, or by activating extremely low levels of pSmad1/5/8. We provide evidence that, although panda mRNA is broadly distributed in the early embryo, local expression of panda mRNA efficiently orients the dorsal-ventral axis and that Panda activity is required locally in the early embryo to specify this axis. Taken together, these findings demonstrate that maternal panda mRNA is both necessary and sufficient to orient the dorsal ventral axis. These results therefore provide evidence that in the highly regulative sea urchin embryo, the activity of spatially restricted maternal factors regulates patterning along the dorsal-ventral axis. PMID- 26352142 TI - Comparative Gene Expression Analyses Identify Luminal and Basal Subtypes of Canine Invasive Urothelial Carcinoma That Mimic Patterns in Human Invasive Bladder Cancer. AB - More than 160,000 people are expected to die from invasive urothelial carcinoma (iUC) this year worldwide. Research in relevant animal models is essential to improving iUC management. Naturally-occurring canine iUC closely resembles human iUC in histopathology, metastatic behavior, and treatment response, and could provide a relevant model for human iUC. The molecular characterization of canine iUC, however, has been limited. Work was conducted to compare gene expression array results between tissue samples from iUC and normal bladder in dogs, with comparison to similar expression array data from human iUC and normal bladder in the literature. Considerable similarities between enrichment patterns of genes in canine and human iUC were observed. These included patterns mirroring basal and luminal subtypes initially observed in human breast cancer and more recently noted in human iUC. Canine iUC samples also exhibited enrichment for genes involved in P53 pathways, as has been reported in human iUC. This is particularly relevant as drugs targeting these genes/pathways in other cancers could be repurposed to treat iUC, with dogs providing a model to optimize therapy. As part of the validation of the results and proof of principal for evaluating individualized targeted therapy, the overexpression of EGFR in canine bladder iUC was confirmed. The similarities in gene expression patterns between dogs and humans add considerably to the value of naturally-occurring canine iUC as a relevant and much needed animal model for human iUC. Furthermore, the finding of expression patterns that cross different pathologically-defined cancers could allow studies of dogs with iUC to help optimize cancer management across multiple cancer types. The work is also expected to lead to a better understanding of the biological importance of the gene expression patterns, and the potential application of the cross-species comparisons approach to other cancer types as well. PMID- 26352143 TI - An Estimation of Private Household Costs to Receive Free Oral Cholera Vaccine in Odisha, India. AB - BACKGROUND: Service provider costs for vaccine delivery have been well documented; however, vaccine recipients' costs have drawn less attention. This research explores the private household out-of-pocket and opportunity costs incurred to receive free oral cholera vaccine during a mass vaccination campaign in rural Odisha, India. METHODS: Following a government-driven oral cholera mass vaccination campaign targeting population over one year of age, a questionnaire based cross-sectional survey was conducted to estimate private household costs among vaccine recipients. The questionnaire captured travel costs as well as time and wage loss for self and accompanying persons. The productivity loss was estimated using three methods: self-reported, government defined minimum daily wages and gross domestic product per capita in Odisha. FINDINGS: On average, families were located 282.7 (SD = 254.5) meters from the nearest vaccination booths. Most family members either walked or bicycled to the vaccination sites and spent on average 26.5 minutes on travel and 15.7 minutes on waiting. Depending upon the methodology, the estimated productivity loss due to potential foregone income ranged from $0.15 to $0.29 per dose of cholera vaccine received. The private household cost of receiving oral cholera vaccine constituted 24.6% to 38.0% of overall vaccine delivery costs. INTERPRETATION: The private household costs resulting from productivity loss for receiving a free oral cholera vaccine is a substantial proportion of overall vaccine delivery cost and may influence vaccine uptake. Policy makers and program managers need to recognize the importance of private costs and consider how to balance programmatic delivery costs with private household costs to receive vaccines. PMID- 26352145 TI - Mark-Release-Recapture Reveals Extensive Movement of Bed Bugs (Cimex lectularius L.) within and between Apartments. AB - Understanding movement and dispersal of the common bed bug (Cimex lectularius L.) under field conditions is important in the control of infestations and for managing the spread of bed bugs to new locations. We investigated bed bug movement within and between apartments using mark-release-recapture (m-r-r) technique combined with apartment-wide monitoring using pitfall-style interceptors. Bed bugs were collected, marked, and released in six apartments. The distribution of marked and unmarked bed bugs in these apartments and their 24 neighboring units were monitored over 32 days. Extensive movement of marked bed bugs within and between apartments occurred regardless of the number of bed bugs released or presence/absence of a host. Comparison of marked and unmarked bed bug distributions confirms that the extensive bed bug activity observed was not an artifact of the m-r-r technique used. Marked bed bugs were recovered in apartments neighboring five of six m-r-r apartments. Their dispersal rates at 14 or 15 d were 0.0-5.0%. The estimated number of bed bugs per apartment in the six m-r-r apartments was 2,433-14,291 at 4-7 d after release. Longevity of bed bugs in the absence of a host was recorded in a vacant apartment. Marked large nymphs (3rd- 5th instar), adult females, and adult males continued to be recovered up to 57, 113, and 134 d after host absence, respectively. Among the naturally existing unmarked bed bugs, unfed small nymphs (1st- 2nd instar) were recovered up to 134 d; large nymphs and adults were still found at 155 d when the study ended. Our findings provide important insight into the behavioral ecology of bed bugs in infested apartments and have significant implications in regards to eradication programs and managing the spread of bed bugs within multi-occupancy dwellings. PMID- 26352144 TI - Ultra-High-Resolution Computed Tomography of the Lung: Image Quality of a Prototype Scanner. AB - PURPOSE: The image noise and image quality of a prototype ultra-high-resolution computed tomography (U-HRCT) scanner was evaluated and compared with those of conventional high-resolution CT (C-HRCT) scanners. MATERIALS AND METHODS: This study was approved by the institutional review board. A U-HRCT scanner prototype with 0.25 mm x 4 rows and operating at 120 mAs was used. The C-HRCT images were obtained using a 0.5 mm x 16 or 0.5 mm x 64 detector-row CT scanner operating at 150 mAs. Images from both scanners were reconstructed at 0.1-mm intervals; the slice thickness was 0.25 mm for the U-HRCT scanner and 0.5 mm for the C-HRCT scanners. For both scanners, the display field of view was 80 mm. The image noise of each scanner was evaluated using a phantom. U-HRCT and C-HRCT images of 53 images selected from 37 lung nodules were then observed and graded using a 5 point score by 10 board-certified thoracic radiologists. The images were presented to the observers randomly and in a blinded manner. RESULTS: The image noise for U-HRCT (100.87 +/- 0.51 Hounsfield units [HU]) was greater than that for C-HRCT (40.41 +/- 0.52 HU; P < .0001). The image quality of U-HRCT was graded as superior to that of C-HRCT (P < .0001) for all of the following parameters that were examined: margins of subsolid and solid nodules, edges of solid components and pulmonary vessels in subsolid nodules, air bronchograms, pleural indentations, margins of pulmonary vessels, edges of bronchi, and interlobar fissures. CONCLUSION: Despite a larger image noise, the prototype U-HRCT scanner had a significantly better image quality than the C-HRCT scanners. PMID- 26352146 TI - Optimism Bias in Fans and Sports Reporters. AB - People are optimistic about their prospects relative to others. However, existing studies can be difficult to interpret because outcomes are not zero-sum. For example, one person avoiding cancer does not necessitate that another person develops cancer. Ideally, optimism bias would be evaluated within a closed formal system to establish with certainty the extent of the bias and the associated environmental factors, such that optimism bias is demonstrated when a population is internally inconsistent. Accordingly, we asked NFL fans to predict how many games teams they liked and disliked would win in the 2015 season. Fans, like ESPN reporters assigned to cover a team, were overly optimistic about their team's prospects. The opposite pattern was found for teams that fans disliked. Optimism may flourish because year-to-year team results are marked by auto-correlation and regression to the group mean (i.e., good teams stay good, but bad teams improve). PMID- 26352147 TI - A New Approach to Investigate the Association between Brain Functional Connectivity and Disease Characteristics of Attention-Deficit/Hyperactivity Disorder: Topological Neuroimaging Data Analysis. AB - BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is currently diagnosed by a diagnostic interview, mainly based on subjective reports from parents or teachers. It is necessary to develop methods that rely on objectively measureable neurobiological data to assess brain-behavior relationship in patients with ADHD. We investigated the application of a topological data analysis tool, Mapper, to analyze the brain functional connectivity data from ADHD patients. METHODS: To quantify the disease severity using the neuroimaging data, the decomposition of individual functional networks into normal and disease components by the healthy state model (HSM) was performed, and the magnitude of the disease component (MDC) was computed. Topological data analysis using Mapper was performed to distinguish children with ADHD (n = 196) from typically developing controls (TDC) (n = 214). RESULTS: In the topological data analysis, the partial clustering results of patients with ADHD and normal subjects were shown in a chain-like graph. In the correlation analysis, the MDC showed a significant increase with lower intelligence scores in TDC. We also found that the rates of comorbidity in ADHD significantly increased when the deviation of the functional connectivity from HSM was large. In addition, a significant correlation between ADHD symptom severity and MDC was found in part of the dataset. CONCLUSIONS: The application of HSM and topological data analysis methods in assessing the brain functional connectivity seem to be promising tools to quantify ADHD symptom severity and to reveal the hidden relationship between clinical phenotypic variables and brain connectivity. PMID- 26352148 TI - Association between Prediagnostic Allergy-Related Serum Cytokines and Glioma. AB - Allergy is inversely related to glioma risk. To determine whether prediagnostic allergy-related serum proteins are associated with glioma, we conducted a nested case-control study of seven cytokines (IL4, IL13, IL5, IL6, IL10, IFNG, TGFB2), two soluble cytokine receptors (sIL4RA, sIL13RA2) and three allergy-related transcription factors (FOXP3, STAT3, STAT6) using serum specimens from the Janus Serum Bank Cohort in Oslo, Norway. Blood donors subsequently diagnosed with glioma (n = 487) were matched to controls (n = 487) on age and date of blood draw and sex. We first estimated individual effects of the 12 serum proteins and then interactions between IL4 and IL13 and their receptors using conditional logistic regression. We next tested equality of case-control inter-correlations among the 12 serum proteins. We found that TGFB2 is inversely related to glioblastoma (Odds Ratio (OR) = 0.87, 95% Confidence Interval (CI)) = 0.76, 0.98). In addition, <= 5 years before diagnosis, we observed associations between IL4 (OR = 0.82, 95% CI = 0.66, 1.01), sIL4RA (OR = 0.80, 95% CI = 0.65, 1.00), their interaction (OR = 1.06, 95% CI = 1.01, 1.12) and glioblastoma. This interaction was apparent > 20 years before diagnosis (IL4-sIL4RA OR = 1.20, 95% CI = 1.05, 1.37). Findings for glioma were similar. Case correlations were different from control correlations stratified on time before diagnosis. Five years or less before diagnosis, correlations among case serum proteins were weaker than were those among controls. Our findings suggest that IL4 and sIL4RA reduce glioma risk long before diagnosis and early gliomagenesis affects circulating immune function proteins. PMID- 26352149 TI - Higher Sensitivity of Foxp3+ Treg Compared to Foxp3- Conventional T Cells to TCR Independent Signals for CD69 Induction. AB - T lymphocytes elicit specific responses after recognizing cognate antigen. However, antigen-experienced T cells can also respond to non-cognate stimuli, such as cytokines. CD4+ Foxp3+ regulatory T cells (Treg) exhibit an antigen experienced-like phenotype. Treg can regulate T cell responses in an antigen specific or bystander way, and it is still unclear as to which extent they rely on T cell receptor (TCR) signals. The study of the antigen response of Treg has been hampered by the lack of downstream readouts for TCR stimuli. Here we assess the effects of TCR signals on the expression of a classical marker of early T cell activation, CD69. Although it can be induced following cytokine exposure, CD69 is commonly used as a readout for antigen response on T cells. We established that upon in vitro TCR stimulation CD69 induction on Foxp3+ Treg cells was more dependent on signaling via soluble factors than on TCR activation. By contrast, expression of the activation marker Nur77 was only induced after TCR stimulation. Our data suggest that Treg are more sensitive to TCR-independent signals than Foxp3- cells, which could contribute to their bystander activity. PMID- 26352150 TI - Winter Is Coming: Seasonal Variation in Resting Metabolic Rate of the European Badger (Meles meles). AB - Resting metabolic rate (RMR) is a measure of the minimum energy requirements of an animal at rest, and can give an indication of the costs of somatic maintenance. We measured RMR of free-ranging European badgers (Meles meles) to determine whether differences were related to sex, age and season. Badgers were captured in live-traps and placed individually within a metabolic chamber maintained at 20 +/- 1 degrees C. Resting metabolic rate was determined using an open-circuit respirometry system. Season was significantly correlated with RMR, but no effects of age or sex were detected. Summer RMR values were significantly higher than winter values (mass-adjusted mean +/- standard error: 2366 +/- 70 kJ?d(-1); 1845 +/- 109 kJ?d(-1), respectively), with the percentage difference being 24.7%. While under the influence of anaesthesia, RMR was estimated to be 25.5% lower than the combined average value before administration, and after recovery from anaesthesia. Resting metabolic rate during the autumn and winter was not significantly different to allometric predictions of basal metabolic rate for mustelid species weighing 1 kg or greater, but badgers measured in the summer had values that were higher than predicted. Results suggest that a seasonal reduction in RMR coincides with apparent reductions in physical activity and body temperature as part of the overwintering strategy ('winter lethargy') in badgers. This study contributes to an expanding dataset on the ecophysiology of medium sized carnivores, and emphasises the importance of considering season when making predictions of metabolic rate. PMID- 26352151 TI - When Aspirations Exceed Expectations: Quixotic Hope Increases Depression among Students. AB - A paradox exists in modern schooling: students are simultaneously more positive about the future and more depressed than ever. We suggest that these two phenomena may be linked. Two studies demonstrated that students are more likely to be depressed when educational aspirations exceed expectations. In Study 1 (N = 85) aspiring to a thesis grade higher than one expected predicted greater depression at the beginning and end of the academic year. In Study 2 (N = 2820) aspiring to a level of education (e.g., attending college) higher than one expected to achieve predicted greater depression cross-sectionally and five years later. In both cases the negative effects of aspiring high while expecting low persisted even after controlling for whether or not students achieved their educational aspirations. These findings highlight the danger of teaching students to aspire higher without also investing time and money to ensure that students can reasonably expect to achieve their educational goals. PMID- 26352152 TI - Occupational hazards and diseases among workers in emergency services: a literature review with special emphasis on Chile. AB - BACKGROUND: Healthcare workers face the risk of accidents and illnesses related to their occupation. Psychological stress, exposure to communicable diseases and violence are perhaps the most significant ones. Workers in emergency services are more likely to be subjected to these risks than healthcare workers in other areas. This review aims to assess current international literature regarding this situation and more specifically the treatment that this issue has had in Chile. METHODS: We based the review mainly on PubMed/MEDLINE. The general search strategy included the following keywords: health personnel, emergency medical services and occupational diseases combined with other specific words. We also reviewed the state of prevention for occupational hazards in the emergency services. RESULTS: More than 70 studies addressing the issue of one or another occupational hazard in emergency services were detected. In Chile 12 studies refer to the issue of occupational risks in healthcare workers and at least two of them focus on emergency services. CONCLUSIONS: The review evaluates the overall picture of the risks and illnesses of emergency services health workers but does not analyze each of the risks in depth. We recommend delving deeper into the issue of occupational hazards of emergency service healthcare workers in order to help improve and evaluate preventative measures. PMID- 26352153 TI - Layer-by-layer grown scalable redox-active ruthenium-based molecular multilayer thin films for electrochemical applications and beyond. AB - Here we report the first study on the electrochemical energy storage application of a surface-immobilized ruthenium complex multilayer thin film with anion storage capability. We employed a novel dinuclear ruthenium complex with tetrapodal anchoring groups to build well-ordered redox-active multilayer coatings on an indium tin oxide (ITO) surface using a layer-by-layer self assembly process. Cyclic voltammetry (CV), UV-Visible (UV-Vis) and Raman spectroscopy showed a linear increase of peak current, absorbance and Raman intensities, respectively with the number of layers. These results indicate the formation of well-ordered multilayers of the ruthenium complex on ITO, which is further supported by the X-ray photoelectron spectroscopy analysis. The thickness of the layers can be controlled with nanometer precision. In particular, the thickest layer studied (65 molecular layers and approx. 120 nm thick) demonstrated fast electrochemical oxidation/reduction, indicating a very low attenuation of the charge transfer within the multilayer. In situ-UV-Vis and resonance Raman spectroscopy results demonstrated the reversible electrochromic/redox behavior of the ruthenium complex multilayered films on ITO with respect to the electrode potential, which is an ideal prerequisite for e.g. smart electrochemical energy storage applications. Galvanostatic charge-discharge experiments demonstrated a pseudocapacitor behavior of the multilayer film with a good specific capacitance of 92.2 F g(-1) at a current density of 10 MUA cm(-2) and an excellent cycling stability. As demonstrated in our prototypical experiments, the fine control of physicochemical properties at nanometer scale, relatively good stability of layers under ambient conditions makes the multilayer coatings of this type an excellent material for e.g. electrochemical energy storage, as interlayers in inverted bulk heterojunction solar cell applications and as functional components in molecular electronics applications. PMID- 26352154 TI - Use of preoperative factors including urodynamic evaluations and nerve-sparing status for predicting urinary continence recovery after robot-assisted radical prostatectomy: Nerve-sparing technique contributes to the reduction of postprostatectomy incontinence. AB - AIMS: To examine which preoperative factors, including urodynamic evaluations, and operative procedures could predict continence status after robot-assisted radical prostatectomy (RARP) in this study. MATERIALS AND METHODS: Univariate and multivariate logistic regression analyses of preoperative factors such as age, body mass index, prostate-specific antigen level before biopsy, prostate size before surgery, membranous urethral length measured using magnetic resonance imaging (MRI), bladder compliance and maximum urethral closure pressure (MUCP) measured by urodynamic study (UDS), and nerve-sparing (NS) status predicting 24 hr pad test >2 g/day at 1 year after RARP were examined in 111 patients enrolled in this study. RESULTS: The number of patients with incontinence at 1 year after RARP was 39 (35.1%). The only predictive factor for urinary continence was NS grades. To investigate the contribution of NS to urinary continence, 84 patients underwent UDS three times; before, immediately after, and 1 year after RARP. Chronological UDS revealed that recovery patterns of storage and voiding functions were the same among non-NS, unilateral-NS, and bilateral-NS groups, and that higher degrees of NS contributed to lesser decreases in MUCP and longer functional urethral length (FUL) after RARP. CONCLUSION: Preoperative factors, including the results of UDS, could not predict continence 1 year after RARP. The NS procedure contributed to continence status. NS favorably affected MUCP and FUL; however, it did not affect bladder function after RARP. Neurourol. Urodynam. 35:1034-1039, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26352155 TI - Induction differentiation of rabbit adipose-derived stromal cells into insulin producing cells in vitro. AB - Mesenchymal stem cells (MSCs) with the ability to differentiate into insulin producing cells (IPCs) have become the most promising means of therapy for diabetes mellitus. Adipose-derived stromal cells (AdSCs), having similar characteristics to those of derived MSCs, are known to exhibit extensive proliferation potential and are able to undergo multi-lineage differentiation. Whether AdSCs can differentiate into insulin-producing cells (IPCs), however, has not been sufficiently elucidated. Therefore, the present study sought to investigate the in vitro differentiation of rabbit (r)AdSCs into IPCs, which may provide an abundant source of cells to treat diabetes. rADSCs were obtained from liposuction aspirates and then induced with glucagon-like peptide-1 and nicotinamide to differentiate into insulin-secreting cells. Differentiation was evaluated by the analysis of morphology, dithizone (DTZ) staining, reverse transcription polymerase chain reaction (RT-PCR), western blot analysis and a glucose challenge assay with detection of insulin secretion by ELISA. Morphological phase-contrast microscopic observation revealed typical islet-like cell clusters following 21 days of differentiation. DTZ staining also showed that differentiated cells were positive and undifferentiated cells were negative for insulin production. Furthermore, RT-PCR analysis confirmed the mRNA expression of insulin, PDX1 and GLUT2 in differentiated cells. Western blot analysis showed that insulin was expressed by the differentiated cells. The glucose challenge assay showed that insulin secretion of the IPCs was in a glucose dependent manner. These findings implied that AdSCs are able to differentiate into IPC in vitro, and are therefore promising candidates for the treatment of diabetes. PMID- 26352156 TI - A wavelength dependent investigation of the indole photophysics via ionization and fragmentation pump-probe spectroscopies. AB - A wavelength dependent study investigating the low-lying (1)La and (1)Lb states, both possessing (1)pipi* character, and the (1)pisigma* state in the deactivation process of indole is presented here. Relaxation dynamics following excitation at 241, 250, 260, 270, 273, and 282 nm are examined using three gas-phase, pump probe spectroscopic techniques: (1) hydrogen atom (H-atom) time-resolved kinetic energy release (TR-KER), (2) time-resolved photoelectron spectroscopy (TR-PES), and (3) time-resolved ion yield (TR-IY). Applied in combination, a more complete picture of the indole relaxation dynamics may be gleaned. For instance, TR-PES experiments directly observe all relaxation pathways by probing the evolution of the excited states following photoexcitation; whereas, TR-KER measurements indirectly, yet specifically, probe for (1)pisigma*-state activity through the detection of H-atoms eliminated along the indole nitrogen-hydrogen (N-H) stretch coordinate-a possible outcome of (1)pisigma*-state relaxation in indole. In addition, mass information obtained via TR-IY monitors fragmentation dynamics that may occur within the neutral electronically excited and/or cationic states. The work herein assesses the onset and importance of the (1)pisigma* state at various pump wavelengths by systematically tuning across the ultraviolet absorption spectrum of indole with a particular focus on those pump wavelengths longer than 263 nm, where the involvement of the (1)pisigma* state is under current debate. As far as this experimental work is concerned, there does not appear to be any significant involvement by the (1)pisigma* state in the indole relaxation processes following excitation at 270, 273, or 282 nm. This investigation also evaluates the primary orbital promotions contributing to the (1)La, (1)Lb, and (1)pisigma* transitions based on ionization preferences observed in TR-PES spectra. Relaxation time constants associated with dynamics along these states are also reported for excitation at all of the aforementioned pump wavelengths and are used to pinpoint the origin of the discrepancies found in the literature. In this context, advantages and disadvantages of the three experimental techniques are discussed. PMID- 26352157 TI - Abstracts from the 7th International Conference on cGMP Generators, Effectors and Therapeutic Implications. PMID- 26352158 TI - Gait Speeds Associated with Anxiety Responses to Pain in Osteoarthritis Patients. AB - OBJECTIVE: Patients with lower limbs osteoarthritis (OA) had slower walking speeds than healthy. Gait speed, which is associated with leg muscle strength, is a consistent predictor of health and functional status. The effects of pain and pain-related psychological constructs for gait speeds have been uncertain. Therefore, we investigated whether gait speed in patients with OA of lower limbs is associated with pain-related psychological constructs using a performance based measure. METHODS: The study group comprised 59 patients with advanced knee or hip OA. Gait speeds were measured at comfortable and maximum levels during 10 m walks. Covariates included 1) pain intensity measured with a visual analogue scale (VAS), 2) psychological constructs measured with a short-version pain anxiety symptoms scale (PASS-20) and the hospital anxiety and depression scale (HADS), and 3) bilateral knee extensor and hip abductor muscle strength. Each variable was subjected to multivariate analysis with gait speed. RESULTS: Single regression analysis showed that gait speeds were significantly correlated with VAS and PASS-20 scores, and muscle strength, not with HADS. Multiple regression analysis showed that PASS-20 score was significant correlating factor for gait speeds. CONCLUSIONS: Anxiety-related responses to pain were significant correlating factor for gait speeds, in patients with OA of lower limbs. PMID- 26352159 TI - Synthesis and structural characterisation of bismuth(III) hydroxamates and their activity against Helicobacter pylori. AB - Seven new bismuth(iii) hydroxamate complexes derived from the hydroxamic acids N methylfurohydroxamic acid (H-MFHA), N-benzoyl-N-phenylhydroxamic acid (H-BPHA), salicylhydroxamic acid (H2-SHA), benzohydroxamic acid (H2-BHA), and acetohydroxamic acid (H2-AHA) have been synthesized and characterized. The complexes formed are either tris-hydroxamato complexes containing only mono anionic ligands, [Bi(H-SHA)3], [Bi(MFHA)3] and [Bi(BPHA)3]; mixed-anion complexes, [Bi(SHA)(H-SHA)] and [Bi(AHA)(H-AHA)]; and potassium bismuthate complexes, K[Bi(SHA)2] and K[Bi(BHA)2]. The solid-state structure of three complexes has been determined through single crystal X-ray diffraction; [Bi(MFHA)3]2.Me2C[double bond, length as m-dash]O, {[Bi(SHA)(H SHA)(DMSO)2][Bi(SHA)(H-SHA)(DMSO)].DMSO}infinity and [Bi(BPHA)3]2.2EtOH. All the complexes and their parent acids were assessed for the bactericidal activity against three strains of Helicobacter pylori (26695, B128 and 251). Of the acids, only acetohydroxamic acid showed any activity at low concentrations (MIC 6.25 MUg mL(-1); 83.26 MUM) while the others were not toxic below 25 MUg mL(-1). In contrast, their bismuth(iii) complexes all showed excellent activity across all three strains (e.g. 0.28 MUM for [Bi(H-SHA)3] to 6.01 MUM for K[Bi(BHA)2] against strain 251) with only minor variations in activity being both ligand and composition dependant. PMID- 26352161 TI - The Thrombospondin1-TGF-beta Pathway and Glaucoma. AB - Glaucoma is characterized by abnormal remodeling of the extracellular matrix (ECM) in the trabecular meshwork and in the connective tissue beams of the lamina cribrosa (LC) at the optic nerve head (ONH), which is associated with axonal damage. Mechanical strain can stimulate ECM remodeling and increased expression of matricellular proteins. Thrombospondins 1 and 2 are induced by cyclic mechanical strain in the eye in both the trabecular meshwork and in the LC region of the ONH. TGF-betas 1 and 2 are increased in glaucoma and play a role in the pathologic remodeling of the ECM in the eye in glaucoma. In this study, we address the role of thrombospondin1 as a regulator of latent TGF-beta activation and discuss the potential therapeutic use of antagonists of the thrombospondin1 TGF-beta pathway for treatment of glaucoma. PMID- 26352160 TI - Thrombospondin-1-Based Antiangiogenic Therapy. AB - Ocular angiogenesis is one of the underlying causes of blindness and vision impairment and may occur in a spectrum of disorders, including diabetic retinopathy, neovascular age-related macular degeneration, retinal artery or vein occlusion, and retinopathy of prematurity. As such, strategies to inhibit angiogenesis by suppressing vascular endothelial growth factor activity have proven to be effective in the clinic for the treatment of eye diseases. A complementary approach would be to increase the level of naturally occurring inhibitors of angiogenesis, such as thrombospondin (TSP)-1. This article summarizes the development of TSP-1-based inhibitors of angiogenesis. PMID- 26352162 TI - TSP-1 Deficiency Alters Ocular Microbiota: Implications for Sjogren's Syndrome Pathogenesis. AB - PURPOSE: The potential role of commensals as triggering factors that promote inflammation in dry eye disease has not been explored. The objective of this study was to evaluate whether ocular microbiota changes with the onset of dry eye disease in thrombospondin-1-deficient (TSP-1(-/-)) mice, a strain that develops Sjogren's syndrome-like disease. METHODS: Conjunctival swabs were collected from TSP-1(-/-) and C57BL/6 mice and analyzed for bacterial presence. Opsonophagocytosis of the bacterial conjunctival isolates derived from the aged TSP-1(-/-) mice by neutrophils derived from either TSP-1(-/-) or C57BL/6 bone marrow was evaluated. The bactericidal activities of TSP-1-derived peptide were examined. RESULTS: We found that in TSP-1(-/-) mice, the conjunctival colonization with Staphylococcus aureus and coagulase negative staphylococci sp (CNS) species was significantly increased with aging and preceded that of the wild-type C57BL/6 control mice. This correlated with increased neutrophil infiltration into the conjunctiva of the TSP-1(-/-) mice, suggesting that TSP-1 plays a significant role in regulating immunity to commensals. Accordingly, the TSP-1(-/-) PMNs opsonophagocytozed the ocular commensals less efficiently than the TSP-1-sufficient neutrophils. Furthermore, a TSP-1-derived peptide, 4N1K, exhibited significant antimicrobial activity when compared to a control peptide against commensal sp. CONCLUSION: These studies illustrate that alterations in the commensal frequency occur in the early stages of development of Sjogren's like pathology and suggest that interventions that limit commensal outgrowth such as the use of TSP-1-derived peptides could be used for treatment during the early stages of the disease to reduce the commensal burden and ensuing inflammation. PMID- 26352163 TI - Transcriptomic Analysis of Human Primary Bronchial Epithelial Cells after Chloropicrin Treatment. AB - Chloropicrin is a vaporizing toxic irritant that poses a risk to human health if inhaled, but the mechanism of its toxicity in the respiratory tract is poorly understood. Here, we exposed human primary bronchial epithelial cells (HBEpC) to two concentrations of chloropicrin (10-50 MUM) for 6 or 48 h and used genomic microarray, flow cytometry, and TEM-analysis to monitor cellular responses to the exposures. The overall number of differentially expressed transcripts with a fold change > +/- 2 compared to controls increased with longer exposure times. The initial response was activation of genes with a higher number of up- (512 by 10 MUM and 408 by 40 MUM chloropicrin) rather than down-regulated transcripts (40 by 10 MUM and 215 by 40 MUM chloropicrin) at 6 h seen with both exposure concentrations. The number of down-regulated transcripts, however, increased with the exposure time. The differentially regulated transcripts were further examined for enriched Gene Ontology Terms (GO) and KEGG-pathways. According to this analysis, the "ribosome" and "oxidative phosphorylation" were the KEGG-pathways predominantly affected by the exposure. The predominantly affected (GO) biological processes were "protein metabolic process" including "translation," "cellular protein complex assembly," and "response to unfolded protein." Furthermore, the top pathways, "NRF2-activated oxidative stress" and "Ah-receptor signaling," were enriched in our data sets by IPA-analysis. Real time qPCR assay of six selected genes agreed with the microarray analysis. In addition, chloropicrin exposure increased the numbers of late S and/or G2/M-phase cells as analyzed by flow cytometry and induced autophagy as revealed by electron microscopy. The targets identified are critical for vital cellular functions reflecting acute toxic responses and are potential causes for the reduced viability of epithelial cells after chloropicrin exposure. PMID- 26352164 TI - Discharge educational strategies for reduction of vascular events (DESERVE): design and methods. AB - RATIONALE: Stroke and vascular risk factors disproportionately affect minority populations, with Blacks and Hispanics experiencing a 2.5- and 2.0-fold greater risk compared with whites, respectively. Patients with transient ischemic attacks and mild, nondisabling strokes tend to have short hospital stays, rapid discharges, and inaccurate perceptions of vascular risk. AIM: The primary aim of the Discharge Educational Strategies for Reduction of Vascular Events (DESERVE) trial is to evaluate the efficacy of a novel community health worker-based multilevel discharge intervention vs. standard discharge care on vascular risk reduction among racially/ethnically diverse transient ischemic attack/mild stroke patients at one-year postdischarge. We hypothesize that those randomized to the discharge intervention will have reduced modifiable vascular risk factors as determined by systolic blood pressure compared with those receiving usual care. SAMPLE SIZE ESTIMATES: Given 300 subjects per group and alpha of 0.05, the power to detect a 6 mmHg reduction in systolic blood pressure is 89%. DESIGN: DESERVE trial is a prospective, randomized, multicenter clinical trial of a novel discharge behavioral intervention. Patients with transient ischemic attack/mild stroke are randomized during hospitalization or emergency room visit to intervention or usual care. Intervention begins prior to discharge and continues postdischarge. STUDY OUTCOMES: The primary outcome is difference in systolic blood pressure reduction between groups at 12 months. Secondary outcomes include between-group differences in change in glycated hemoglobin, smoking rates, medication adherence, and recurrent stroke/transient ischemic attack at 12 months. DISCUSSION: DESERVE will evaluate whether a novel discharge education strategy leads to improved risk factor control in a racially diverse population. PMID- 26352165 TI - Robotic-assisted laparoscopic nephrectomy. AB - The introduction of robot-assisted surgery has helped practitioners implement laparoscopic approached to complex retroperitoneal and renal surgery. Urologists are now more frequently completing surgeries such as radical nephroureterectomy, radical nephrectomy with IVC thrombectomy, and retroperitoneal lymphadentectomy via a laparoscopic approach than ever before. This review discusses the rational of the above surgeries as well as a technical step-by-step description of our robotic nephroureterectomy surgical approach. PMID- 26352168 TI - Ultra-low dose CT attenuation correction for PET/CT: analysis of sparse view data acquisition and reconstruction algorithms. AB - For PET/CT systems, PET image reconstruction requires corresponding CT images for anatomical localization and attenuation correction. In the case of PET respiratory gating, multiple gated CT scans can offer phase-matched attenuation and motion correction, at the expense of increased radiation dose. We aim to minimize the dose of the CT scan, while preserving adequate image quality for the purpose of PET attenuation correction by introducing sparse view CT data acquisition.We investigated sparse view CT acquisition protocols resulting in ultra-low dose CT scans designed for PET attenuation correction. We analyzed the tradeoffs between the number of views and the integrated tube current per view for a given dose using CT and PET simulations of a 3D NCAT phantom with lesions inserted into liver and lung. We simulated seven CT acquisition protocols with {984, 328, 123, 41, 24, 12, 8} views per rotation at a gantry speed of 0.35 s. One standard dose and four ultra-low dose levels, namely, 0.35 mAs, 0.175 mAs, 0.0875 mAs, and 0.043 75 mAs, were investigated. Both the analytical Feldkamp, Davis and Kress (FDK) algorithm and the Model Based Iterative Reconstruction (MBIR) algorithm were used for CT image reconstruction. We also evaluated the impact of sinogram interpolation to estimate the missing projection measurements due to sparse view data acquisition. For MBIR, we used a penalized weighted least squares (PWLS) cost function with an approximate total-variation (TV) regularizing penalty function. We compared a tube pulsing mode and a continuous exposure mode for sparse view data acquisition. Global PET ensemble root-mean squares-error (RMSE) and local ensemble lesion activity error were used as quantitative evaluation metrics for PET image quality.With sparse view sampling, it is possible to greatly reduce the CT scan dose when it is primarily used for PET attenuation correction with little or no measureable effect on the PET image. For the four ultra-low dose levels simulated, sparse view protocols with 41 and 24 views best balanced the tradeoff between electronic noise and aliasing artifacts. In terms of lesion activity error and ensemble RMSE of the PET images, these two protocols, when combined with MBIR, are able to provide results that are comparable to the baseline full dose CT scan. View interpolation significantly improves the performance of FDK reconstruction but was not necessary for MBIR. With the more technically feasible continuous exposure data acquisition, the CT images show an increase in azimuthal blur compared to tube pulsing. However, this blurring generally does not have a measureable impact on PET reconstructed images.Our simulations demonstrated that ultra-low-dose CT based attenuation correction can be achieved at dose levels on the order of 0.044 mAs with little impact on PET image quality. Highly sparse 41- or 24- view ultra low dose CT scans are feasible for PET attenuation correction, providing the best tradeoff between electronic noise and view aliasing artifacts. The continuous exposure acquisition mode could potentially be implemented in current commercially available scanners, thus enabling sparse view data acquisition without requiring x-ray tubes capable of operating in a pulsing mode. PMID- 26352169 TI - The role of Pyk2 in the CCR7-mediated regulation of metastasis and viability in squamous cell carcinoma of the head and neck cells in vivo and in vitro. AB - In the present study, we aimed to demonstrate whether praline-rich tyrosine kinase-2 (Pyk2) participates in the chemokine receptor 7 (CCR7) downstream signaling network, and to determine the role of this molecule and the related mechanism in the CCR7-mediated regulation of viability and metastasis in vivo and in vitro of squamous cell carcinoma of the head and neck (SCCHN). We constructed the stable Pyk2 related non-kinase (PRNK)-expressing SCCHN cell line, and examined the viability, apoptosis, migration, invasion and adhesion ability in the transfected and untransfected SCCHN cells. An SCCHN tumor model in nude mice was designed and the tumor growth rate was assayed. E-cadherin and vimentin expression was assessed when Pyk2 was inactivated. We found that the stable PRNK expressing SCCHN cells exhibited low viability, a high rate of apoptosis, low migratory ability, low invasive ability and low adhesion capacity. In the nude mouse body, the tumors formed by these cells grew slowly when compared to the tumor growth in the control group. When Pyk2 was inactivated, CCR7-induced E cadherin and vimentin expression levels were altered. Thus, Pyk2 is a key downstream signaling molecules of CCR7 in SCCHN, which promotes SCCHN tumorigenesis and progression. PMID- 26352171 TI - The efficacy of a combination non-thermal focused ultrasound and radiofrequency device for noninvasive body contouring in Asians. AB - BACKGROUND AND OBJECTIVE: Several studies have been published on the first generation non-thermal focused ultrasound with an average improvement of 0-3.95 cm reported. We aim to investigate the efficacy of the second-generation non thermal focused ultrasound device with a combined radiofrequency hand piece. With the addition of radiofrequency energy, the temperature of the adipose tissue is raised before focused ultrasound is applied. This facilitates the mechanical disruption of fat cells by focused ultrasound. STUDY DESIGN AND METHODS: Twenty subjects were recruited and underwent three treatments biweekly. Caliper reading, abdominal circumference, and standardized photographs were taken with the Vectra((r)) system at all visits. We aim to have the subjects stand and hold the same position and the photograph taken after exhalation. Caliper and circumference measurements carry uncertainty. It is impossible to eliminate all uncertainties but can be improved by having the same trained physician assistant perform the measurement at the same site and taking an average of three readings. Pain score and satisfaction were recorded by means of the visual analogue scale. The efficacy is defined by a statistically significant improvement in circumferential improvement based on intention-to-treat analysis. RESULTS: Seventeen subjects completed the treatment schedule. Abdominal circumference showed statistically significant improvement at 2 weeks post-second treatment (P = 0.023) and almost all subsequent follow-ups. Caliper readings were statistically significant at 2 weeks post-second treatment (P = 0.013) and almost all follow-ups. The mean pain score reported was 2.3 on the visual analog scale and 6% were unsatisfied with the overall treatments. Six incidents of wheal formation appeared immediately after treatment all of which subsided spontaneously within several hours. CONCLUSION: The combination non-thermal focused ultrasound and radiofrequency device is effective for improving body contour in Asians. PMID- 26352170 TI - Rethinking actions: implementation and association. AB - Action processing allows us to move through and interact with the world, as well as understand the movements performed by other people. In recent years, there has been increasing interest in the semantics of actions as differentiated from the semantics of objects. However, as the understanding of action semantics has evolved, it is evident that the existing literature conflates two senses of the word 'action'-one that stems from studies of tool use and the other from event representation. In this paper, we suggest that this issue can be clarified by closely examining differences in how the human parietal and temporal cortices of the brain process action-related stimuli. By contrasting the posterior parietal cortex to the posterolateral temporal cortex, we characterize two complementary action systems in the human brain, each with its own specialization of function. We suggest that these two systems be referred to as the parietal Action Implementation System, and the posterolateral temporal Action Association System. While the frontoparietal system is concerned primarily with how we perform actions, and simulate others' actions, the temporal action system is more involved with processing actions from a third-person, conceptual standpoint. Recent work in cognitive neuroscience of perception and language, as well as the neuroanatomical organization of these brain regions support this distinction. We will discuss the implications of this work for cognition-, language-, and neuroscience-based action research. PMID- 26352172 TI - Electrochemical Measurements of the Kinetics of Inhibition of Two FeFe Hydrogenases by O2 Demonstrate That the Reaction Is Partly Reversible. AB - The mechanism of reaction of FeFe hydrogenases with oxygen has been debated. It is complex, apparently very dependent on the details of the protein structure, and difficult to study using conventional kinetic techniques. Here we build on our recent work on the anaerobic inactivation of the enzyme [Fourmond et al. Nat. Chem. 2014, 4, 336-342] to propose and apply a new method for studying this reaction. Using electrochemical measurements of the turnover rate of hydrogenase, we could resolve the first steps of the inhibition reaction and accurately determine their rates. We show that the two most studied FeFe hydrogenases, from Chlamydomonas reinhardtii and Clostridium acetobutylicum, react with O2 according to the same mechanism, despite the fact that the former is much more O2 sensitive than the latter. Unlike often assumed, both enzymes are reversibly inhibited by a short exposure to O2. This will have to be considered to elucidate the mechanism of inhibition, before any prediction can be made regarding which mutations will improve oxygen resistance. We hope that the approach described herein will prove useful in this respect. PMID- 26352173 TI - PEITC inhibits human brain glioblastoma GBM 8401 cell migration and invasion through the inhibition of uPA, Rho A, and Ras with inhibition of MMP-2, -7 and -9 gene expression. AB - Glioblastoma is the most aggressive primary brain malignancy, and the efficacy of multimodality treatments remains unsatisfactory. Phenethyl isothiocyanate (PEITC), one member of the isothiocyanate family, was found to inhibit the migration and invasion of many types of human cancer cells. In our previous study, PEITC induced the apoptosis of human brain glioblastoma GBM 8401 cells through the extrinsic and intrinsic signaling pathways. In the present study, we first investigated the effects of PEITC on the migration and invasion of GBM 8401 cells. PEITC decreased the migration of GBM 8401 cells in a dose-dependent manner as determined from scratch wound healing and Transwell migration assays. The percentage of inhibition ranged from 46.89 to 15.75%, and from 27.80 to 7.31% after a 48-h treatment of PEITC as determined from the Transwell migration assay and invasion assay, respectively. The western blot analysis indicated that PEITC decreased the levels of proteins associated with migration and invasion, Ras, uPA, RhoA, GRB2, p-p38, p-JNK, p-ERK, p65, SOS1, MMP-2, MMP-9 and MMP-13, in a dose-dependent manner. Real-time PCR analyses revealed that PEITC reduced the mRNA levels of MMP-2, MMP-7, MMP-9 and RhoA in a dose- and time-dependent manner. PEITC exhibited potent anticancer activities through the inhibition of migration and invasion in the GBM 8401 cells. Our findings elucidate the possible molecular mechanisms and signaling pathways of the anti-metastatic effects of PEITC on human brain glioblastoma cells, and PEITC may be considered as a therapeutic agent. PMID- 26352174 TI - Design of an Indolylphosphine Ligand for Reductive Elimination-Demanding Monoarylation of Acetone Using Aryl Chlorides. AB - The rational design of a phosphine ligand for the reductive elimination-demanding Pd-catalyzed mono-alpha-arylation of acetone is demonstrated and reported. The catalyst is tolerant of previously proven challenging electron-deficient aryl chlorides and provides excellent product yields with down to 0.1 mol % Pd. Preliminary investigations suggest that the rate-limiting step for the proposed system is the oxidative addition of aryl chlorides, in which it contradicts previous findings regarding the alpha-arylation of acetone with aryl halides. PMID- 26352176 TI - Editorial considerations on the new clinical and surgical perspectives of Brazilian cardiology. PMID- 26352175 TI - Downregulation of microRNA-33a promotes cyclin-dependent kinase 6, cyclin D1 and PIM1 expression and gastric cancer cell proliferation. AB - Although microRNA-33 (miR-33) family members are known to be involved in the regulation and balancing of cholesterol metabolism, fatty acid oxidation and insulin signaling, their functions in carcinogenesis are controversial and the underlying mechanisms have remained elusive. Gastric cancer is the fourth most common malignancy in the world; however, the dysregulation and function of miR-33 family members in gastric cancer have not been extensively studied. The present study reported that a miR-33 family member, miR-33a, was significantly downregulated in gastric cancer tissues and gastric cancer cell lines. Of note, the expression of miR-33a was inversely correlated with pathological differentiation and metastasis as well as gastric cancer biomarker CA199. A cell counting kit-8 assay showed that transfection of the SGC-7901 gastric cell line with miR-33a-overexpression plasmid inhibited the capability of the cells to proliferate. Furthermore, overexpression of miR-33a led to cell cycle arrest of SGC-7901 cells in G1 phase. In addition, a luciferase reporter assay showed that miR-33a directly targeted cyclin-dependent kinase 6 (CDK6), cyclin D1 (CCND1) and serine/threonine kinase PIM-1. In gastric cancer specimens, the reduced expression of miR-33a was associated with increased expression of CDK-6, CCND1 and PIM1. However, only PIM1 expression was significantly increased in cancer tissues compared with that in their adjacent tissues. The present study revealed that miR-33a was downregulated in gastric cancer tissues and cell lines, while forced overexpression of miR-33a decreased CDK-6, CCND1 and PIM1 expression to inhibit gastric cancer cell proliferation by causing G1 phase arrest. miR-33a overexpression may therefore resemble an efficient strategy for gastric cancer therapy. PMID- 26352177 TI - Executive summary - guideline on telecardiology in the care of patients with acute coronary syndrome and other cardiac diseases. PMID- 26352178 TI - Diastolic function in paced children with cardiac defects: septum vs apex. AB - In children with structural congenital heart disease (CHD), the effects of chronic ventricular pacing on diastolic function are not well known. On the other hand, the beneficial effect of septal pacing over apical pacing is still controversial.The aim of this study was to evaluate the influence of different right ventricular (RV) pacing site on left ventricular (LV) diastolic function in children with cardiac defects.Twenty-nine pediatric patients with complete atrioventricular block (CAVB) and CHD undergoing permanent pacing were prospectively studied. Pacing sites were RV apex (n = 16) and RV septum (n = 13). Echocardiographic assessment was performed before pacemaker implantation and after it, during a mean follow-up of 4.9 years.Compared to RV septum, transmitral E-wave was significantly affected in RV apical pacing (95.38 +/- 9.19 vs 83 +/- 18.75, p = 0.038). Likewise, parameters at the lateral annular tissue Doppler imaging (TDI) were significantly affected in children paced at the RV apex. The E' wave correlated inversely with TDI lateral myocardial performance index (Tei index) (R2= 0.9849, p <= 0.001). RV apex pacing (Odds ratio, 0.648; confidence interval, 0.067-0.652; p = 0.003) and TDI lateral Tei index (Odds ratio, 31.21; confidence interval, 54.6-177.4; p = 0.025) predicted significantly decreased LV diastolic function.Of the two sites studied, RV septum prevents pacing-induced reduction of LV diastolic function. PMID- 26352179 TI - Sudden death in Brazil: epilepsy should be in horizon. PMID- 26352180 TI - Case 6 / 2015 - a 27-year-old male patient with double aortic and pulmonary valve lesion after double valvotomy in childhood. PMID- 26352181 TI - Profound sustained hypotension following renal denervation: a dramatic success? PMID- 26352182 TI - Giant right atrial mass following surgical aortic valve replacement. PMID- 26352183 TI - Subclinical ventricular dysfunction detected by speckle-tracking two years after use of anthracycline. PMID- 26352184 TI - Correction. PMID- 26352186 TI - Do coping strategies mediate the effects of emotional support on emotional well being among Spanish-speaking Latina breast cancer survivors? AB - OBJECTIVE: This study aimed to assess the relationship between emotional social support and emotional well-being among Latina immigrants with breast cancer and test whether two culturally relevant coping strategies, fatalism and acceptance, mediate this relationship. METHODS: One hundred fifty Spanish-speaking Latinas within 1 year of breast cancer diagnosis participating in a randomized trial of a stress management intervention were assessed in person at baseline and via telephone 6 months later. Survey measures included baseline emotional support, fatalism, and acceptance and emotional well-being 6 months later. Generalized linear models estimated direct effects of emotional support on emotional well being and indirect effects through fatalism and acceptance. RESULTS: Mean age was 50.1 (SD = 10.9) years; most women had low education and acculturation levels. Emotional support was negatively associated with fatalism (r = -0.24, p < 0.01) and positively associated with acceptance (r = 0.30, p < 0.001). Emotional support (r = 0.23, p = 0.005) and acceptance (r = 0.28, p = 0.001) were positively associated with emotional well-being, whereas fatalism (r = -0.36, p < 0.0001) was negatively associated with emotional well-being. In multivariable models, emotional support was associated with emotional well-being (b = 0.88, 95% CI: 0.24, 1.52). This direct effect remained significant when additionally controlling for fatalism (b = 0.66, 95% CI: 0.03, 1.30) and acceptance (b = 0.73, 95% CI: 0.09, 1.37) in separate models. There was a significant indirect effect of emotional support on emotional well-being through fatalism (b = 0.21, 95% CI: 0.04, 0.51) as well as a marginally significant effect through acceptance (b = 0.15, 95% CI: 0.001, 0.43). CONCLUSIONS: Emotional support may increase well being among Spanish-speaking Latina cancer survivors by reducing cancer fatalism.Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26352187 TI - Direct Observation of Very Large Zero-Field Splitting in a Tetrahedral Ni(II)Se4 Coordination Complex. AB - The high-spin (S = 1) tetrahedral Ni(II) complex [Ni{(i)Pr2P(Se)NP(Se)(i)Pr2}2] was investigated by magnetometry, spectroscopic, and quantum chemical methods. Angle-resolved magnetometry studies revealed the orientation of the magnetization principal axes. The very large zero-field splitting (zfs), D = 45.40(2) cm(-1), E = 1.91(2) cm(-1), of the complex was accurately determined by far-infrared magnetic spectroscopy, directly observing transitions between the spin sublevels of the triplet ground state. These are the largest zfs values ever determined- directly--for a high-spin Ni(II) complex. Ab initio calculations further probed the electronic structure of the system, elucidating the factors controlling the sign and magnitude of D. The latter is dominated by spin-orbit coupling contributions of the Ni ions, whereas the corresponding effects of the Se atoms are remarkably smaller. PMID- 26352188 TI - The Glycemic Potential of White and Red Rice Affected by Oil Type and Time of Addition. AB - Limited research exists on how different oil types and time of addition affect starch digestibility of rice. This study aimed to assess the starch digestibility of white and red rice prepared with 2 oil types: vegetable oil (unsaturated fat) and ghee (clarified butter, saturated fat) added at 3 different time points during the cooking process ("before": frying raw rice in oil before boiling, "during": adding oil during boiling, and "after": stir-frying cooked rice in oil). Red rice produced a slower digestion rate than white rice. White rice digestibility was not affected by oil type, but was affected by addition time of oil. Adding oil "after" (stir-frying) to white or red rice resulted in higher slowly digestible starch. Red rice cooked using ghee showed the lowest amount of glucose release during in vitro digestion. The addition of ghee "during" (that is boiling with ghee) or "before" (that is frying rice raw with ghee then boiling) cooking showed potential for attenuating the postprandial glycemic response and increasing resistant starch content. This is the first report to show healthier ways of preparing rice. White rice with oil added "after" (stir-fried) may provide a source of sustained glucose and stabilize blood glucose levels. Boiling red rice with ghee or cooking red rice with ghee pilaf-style may provide beneficial effects on postprandial blood glucose and insulin concentrations, and improve colonic health. The encouraging results of the present study justify extending it to an in vivo investigation to conclusively determine the effect of time of addition of fat when rice is cooked on blood glucose homeostasis. PRACTICAL APPLICATION: Rice is a predominant source of energy in most of Asia with excessive consumption of rice being implicated in the rise of type 2 diabetes. Stir-frying white rice can be a source of sustained glucose and provide a stabilizing effect on blood glucose levels. Boiling red rice with ghee or cooking red rice with ghee pilaf-style may provide beneficial effects on postprandial blood glucose and insulin concentrations. This suggests how a single technique of adding fat in the cooking of rice at certain time points may be a useful method in providing taste and lowering glycemia. PMID- 26352189 TI - Formation of the Hydroxyl Radical by Radiative Association. AB - The reaction rate constant for the radiative association of O((3)P) and H((2)S) has been calculated by combining a few different methods and taking account of both direct and resonance-mediated pathways. The latter includes both shape resonances and Feshbach type inverse predissociation. The reaction rate constant is expressed as a function of temperature in the interval 10-30000 K. This reaction may be astrochemically relevant and is expected to be of use in astrochemical networks. PMID- 26352190 TI - Involvement of Phenylalanine 297 in the Construction of the Substrate Pocket of Human Aminopeptidase B. AB - Aminopeptidase B (APB, EC 3.4.11.6) preferentially hydrolyzes the N-terminal basic amino acids of synthetic and peptide substrates and requires a physiological concentration of NaCl for optimal activity. In this study, we used site-directed mutagenesis and molecular modeling to search for an amino acid residue that is critical for the enzymatic properties of human APB. Substitution of Phe297 with Tyr caused a significant decrease in hydrolytic activity toward synthetic and peptide substrates as well as chloride anion sensitivity. Molecular modeling suggests that Phe297 contributes to the construction of the substrate pocket of APB, which is wide enough to hold a chloride anion and allow the interaction of Gln169 with the N-terminal Arg residue of the substrate through bridging with the chloride anion. These results indicate that Phe297 is crucial for the optimal enzymatic activity and chloride anion sensitivity of APB via formation of the optimal structure of the catalytic pocket. PMID- 26352191 TI - Dynamic Nanoparticle-Based Flexible Sensors: Diagnosis of Ovarian Carcinoma from Exhaled Breath. AB - Flexible sensors based on molecularly modified gold nanoparticles (GNPs) were integrated into a dynamic cross-reactive diagnostic sensing array. Each bending state of the GNP-based flexible sensor gives unique nanoparticle spatial organization, altering the interaction between GNP ligands and volatile organic compounds (VOCs), which increases the amount of data obtainable from each sensor. Individual dynamic flexible sensor could selectively detect parts per billion (ppb) level VOCs that are linked with ovarian cancers in exhaled breath and discriminate them from environmental VOCs that exist in exhaled breath samples, but do not relate to ovarian cancer per se. Strain-related response successfully discriminated between exhaled breath collected from control subjects and those with ovarian cancer, with data from a single sensor being sufficient to obtain 82% accuracy, irrespective of important confounding factors, such as tobacco consumption and comorbidities. The approach raises the hope of achieving an extremely simple, inexpensive, portable, and noninvasive diagnostic procedure for cancer and other diseases. PMID- 26352192 TI - Effects of psychosocial interventions on self-efficacy of dementia caregivers: a literature review. AB - INTRODUCTION: Self-efficacy plays an important role in mediating stressors and physical and psychological outcomes in dementia caregiving. OBJECTIVES: This literature review aims to identify, summarize, and critically appraise current evidence on the psychosocial interventions used for enhancing the self-efficacy of caregivers of patients with dementia (PWD). METHODS: A database search from two major web gateways was conducted to identify relevant research articles with an intervention for caregivers of patients with any type of dementia that included self-efficacy as an outcome measure. RESULTS: A total of 14 studies met the criteria. The key findings and characteristics of the interventions were summarized and analyzed. The results showed that caregivers' self-efficacy and other aspects could be improved by psychosocial interventions. CONCLUSION: The efficacy of the interventions for self-efficacy and other outcomes for caregivers and PWD were explored. Recommendations on the effects and significance of various psychosocial interventions for caregivers of PWD in enhancing self-efficacy were discussed. PMID- 26352193 TI - Alcohol Dependence and Genetic Variability in the Serotonin Pathway among Currently and Formerly Alcohol-Dependent Males. AB - BACKGROUND: Genes involved in the serotonin pathway may determine the susceptibility to alcohol dependence and its severity. The present study explored whether specific polymorphisms in the serotonin pathway could be associated with alcohol dependence or alcohol-related psychopathological symptoms. METHODS: The cohort comprised 101 currently and 100 formerly alcohol-dependent males, as well as 97 male healthy blood donors. The following questionnaires were employed: the Alcohol Use Disorders Identification Test, the Zung Depression and Anxiety Scale, the Brief Social Phobia Scale, the Yale-Brown Obsessive Compulsive Scale and Obsessive Compulsive Drinking Scale, and the Buss-Durkee Hostility Inventory. Subjects were genotyped for bi- and triallelic SLC6A4 5-HTTLPR,HTR1A rs6295, and HTR1B rs13212041. RESULTS: Statistical differences in bi- and triallelic SLC6A4 5 HTTLPR genotype distribution were observed between the 3 groups investigated (p = 0.008 and p = 0.023, respectively); however, no gene-dose effect was observed. The severity of the alcohol problems was higher in currently alcohol-dependent subjects with the 5-HTTLPR LL (p = 0.039) and L'L' genotypes (p = 0.027). Formerly dependent subjects with the 5-HTTLPR S'S' genotype showed more social anxiety, depressive, and anxiety traits (p = 0.009, p = 0.006, and p = 0.036, respectively). Healthy controls with the 5-HTTLPR SS genotype showed more traits of social anxiety (p = 0.020). CONCLUSIONS: Our findings suggest that bi- and triallelic SLC6A4 5-HTTLPR has some effects on the severity of alcohol dependence. Triallelic 5-HTTLPR was associated with social anxiety, anxiety, and depressive traits in alcohol-dependent subjects. PMID- 26352194 TI - The anticancer mechanism of 2'-hydroxycinnamaldehyde in human head and neck cancer cells. AB - Cinnamaldehyde has been shown to effectively induce apoptosis in a number of human cancer cells. In the present study, cinnamaldehyde derivative-induced apoptosis and its signaling pathways were assessed in p53-wild (SGT) and p53 mutant (YD-10B) human head and neck cancer cells. The cinnamaldehyde derivatives, 2'-hydroxycinnamaldehyde (HCA) and 2'-benzoyloxycinnamaldehyde (BCA), exhibited powerful anti-proliferative effects on SGT and YD-10B cells. The apoptotic effect induced by HCA or BCA was supported by caspase-3, -7, -9 and PARP activation, and confirmed by Annexin V-FITC/PI double staining. HCA induced the expression of p21 in both SGT and YD-10B cells. Furthermore, HCA induced the level of pro-apoptotic Bak1 expression while decreasing the level of anti-apoptotic Bcl-2 in both cell lines, suggesting that HCA induced the cell death pathway in a p53-independent manner. HCA also induced the expression of LC3B in SGT and YD-10B cells. Following pre-incubation with the autophagy inhibitor 3-MA, HCA-induced apoptosis was largely increased in SGT cells, while inhibited in YD-10B cells, suggesting that autophagy may actively contribute to HCA-induced apoptosis. Taken together, these observations suggest that HCA may be an effective therapeutic agent in the treatment of head and neck cancer regardless of p53 status. PMID- 26352195 TI - Murine Cyp3a knockout chimeric mice with humanized liver: prediction of the metabolic profile of nefazodone in humans. AB - Chimeric mice with humanized livers (PXB mice) are used to investigate the metabolism and pharmacokinetics of drugs in humans. However, residual murine enzymatic activities derived from the liver and the presence of mouse small intestinal metabolism can hamper the prediction of human drug metabolism. Recently murine Cytochrome P450 3a gene knockout chimeric mice with humanized livers (Cyp3a KO CM) were developed. To evaluate the prediction of drug metabolism, nefazodone (NEF) was administered orally at 10 mg/kg to the following mouse strains: Cyp3a KO CM, murine Cyp3a gene knockout (Cyp3a KO), PXB and severe combined immunodeficiency (SCID) mice. Liquid chromatography-mass spectrometry was used for metabolic profiling of plasma, urine and bile. The prediction of human metabolite levels such as hydroxy nefazodone (OH-NEF), triazoledione form (TD), m-chlorophenylpiperazine and dealkyl metabolites in Cyp3a KO CM was superior to that in Cyp3a KO, PXB or SCID mice. Further, clinical exposure levels of NEF, OH-NEF and TD were reproduced in Cyp3a KO CM. In contrast, NEF was rapidly metabolized to TD in both PXB and SCID mice but not in Cyp3a KO mice, suggesting that murine CYP3A is involved in the elimination of NEF in these mice. These findings demonstrate that the metabolic profile of NEF in Cyp3a KO CM differs qualitatively and quantitatively from that in PXB mice due to the higher metabolic rate of NEF and its metabolites via murine CYP3A. Therefore Cyp3a KO CM might be useful in predicting the metabolic profiles of drug candidates in humans. PMID- 26352196 TI - Need for a roadmap for development of a coordinated national registry programme. AB - Clinical quality registries are an overlooked and under-funded arm of clinical research in Australia. Registries are databases for patients with a particular disease, or who undergo a procedure, or use a health resource. Registries, where properly funded and universally adopted, have provided substantial benefits to the quality of healthcare and, in some cases, have had demonstrable effect in reducing costs. There is a lack of a coordinated programme for both funding and development of registries in Australia. A coordinated effort is required to address key gaps in registry coverage and ensure registries comply with appropriate technical and operating principles, and target areas where registries can add value to the health system. This will ensure that Australia is competitive with its international peers in this dynamic environment. PMID- 26352197 TI - Is there an intramolecular hydrogen bond in 2-halophenols? A theoretical and spectroscopic investigation. AB - The Abraham solute hydrogen bond acidity parameter A can be derived both from physical methods, A(Gen) and NMR experiments, A(NMR) and results for a large number of hydroxylic solutes show that the two methods agreed very well. However for halophenols the values of A(NMR) were not consistent with the A(Gen) values. The values of A(NMR) suggest that there is no intra-molecular hydrogen bonding in any of the 2-halophenols. In contrast the values of A(Gen) indicate that there is no intra-molecular hydrogen bonding in 2-fluorophenol, but weak intra-molecular hydrogen bonding in 2-chloro, 2-bromo, and 2-iodo-phenol. In view of this uncertainty in the presence or absence of intra-molecular H-bonds in the 2 halophenols, a detailed investigation of the methods used in the literature is presented together with a novel NMR method to determine the ratio of cis and trans forms in these compounds. The experimental data is complemented by a detailed theoretical analysis of the structures and bonding in these molecules to assess the presence or absence of an intra-molecular H-bond. We conclude that there is weak hydrogen bonding in 2-chloro, 2-bromo and 2-iodophenol but very little in 2-fluorophenol. PMID- 26352198 TI - Magnetic graphitic carbon nitride: its application in the C-H activation of amines. AB - Magnetic graphitic carbon nitride, Fe@g-C3N4, has been synthesized by adorning a graphitic carbon nitride (g-C3N4) support with iron oxide via non-covalent interaction. The magnetically recyclable catalyst showed excellent reactivity for the expeditious C-H activation and cyanation of amines. PMID- 26352199 TI - Traumatic brain injury: a risk factor for neurodegenerative diseases. AB - Traumatic brain injury (TBI), a major global health and socioeconomic problem, is now established as a chronic disease process with a broad spectrum of pathophysiological symptoms followed by long-term disabilities. It triggers multiple and multidirectional biochemical events that lead to neurodegeneration and cognitive impairment. Recent studies have presented strong evidence that patients with TBI history have a tendency to develop proteinopathy, which is the pathophysiological feature of neurodegenerative disorders such as Alzheimer disease (AD), chronic traumatic encephalopathy (CTE), and amyotrophic lateral sclerosis (ALS). This review mainly focuses on mechanisms related to AD, CTE, and ALS that are induced after TBI and their relevance to the advancement of these neurodegenerative diseases. This review encompasses acute effects and chronic neurodegenerative consequences after TBI for a better understanding of TBI induced neuronal death and to design therapies that will effectively treat patients in the primary or secondary progressive stages. PMID- 26352200 TI - Permanent dynamic transporter-mediated turnover of glutamate across the plasma membrane of presynaptic nerve terminals: arguments in favor and against. AB - Mechanisms for maintenance of the extracellular level of glutamate in brain tissue and its regulation still remain almost unclear, and criticism of the current paradigm of glutamate transport and homeostasis has recently appeared. The main premise for this study is the existence of a definite and non-negligible concentration of ambient glutamate between the episodes of exocytotic release in our experiments with rat brain nerve terminals (synaptosomes), despite the existence of a very potent Na+-dependent glutamate uptake. Glutamate transporter reversal is considered as the main mechanisms of glutamate release under special conditions of energy deprivation, hypoxia, hypoglycemia, brain trauma, and stroke, underlying an increase in the ambient glutamate concentration and development of excitotoxicity. In the present study, a new vision on transporter mediated release of glutamate as one of the main mechanisms involved in the maintenance of definite concentration of ambient glutamate under normal energetical status of nerve terminals is forwarded. It has been suggested that glutamate transporters act effectively in outward direction in a non-pathological manner, and this process is thermodynamically synchronized with uptake and provides effective outward glutamate current, thereby establishing and maintaining permanent and dynamic glutamatein/glutamate(out) gradient and turnover across the plasma membrane. In this context, non-transporter tonic glutamate release by diffusion, spontaneous exocytosis, cystine-glutamate exchanger, and leakage through anion channels can be considered as a permanently added 'new' exogenous substrate using two-substrate kinetic model calculations. Permanent glutamate turnover is of value for tonic activation of post/presynaptic glutamate receptors, long-term potentiation, memory formation, etc. Counterarguments against this mechanism are also considered. PMID- 26352201 TI - Antimicrobial triterpenes from the stem bark of Crossopteryx febrifuga. AB - Phytochemical investigation of the stem bark extract of Crossopteryx febrifuga resulted in the isolation of epimeric mixtures of 3beta-urs-12,20(30)-diene-27,28 dioic acid and 18-epi-3beta-urs-12,20(30)-diene-27,28-dioic acid (1), as well as: 3beta-D-glucopyranosylurs-12,20(30)-diene-27,28-dioic acid and 18-epi-3beta-D glucopyranosylurs-12,20(30)-diene-27,28-dioic acid (2), together with some known compounds such as the monoglyceride of palmitic acid, as well as beta-sitosterol and its glucoside. The structures of the isolated compounds were determined by application of spectroscopic methods. The MeOH extract and compounds 1 and 2 were examined for antimicrobial activity in in vitro assays against bacteria (Enterobacter aerogenes ATCC13048, Escherichia coli ATCC8739, Klebsiella pneumoniae ATCC11296, Staphylococcus aureus) and fungi (Candida parapsilosis, Candida albicans ATCC 9002 and Cryptococcus neoformans IP 90526). The tested samples showed selective activities. The antibacterial and antifungal activities of compound 2 (MIC=8-64 MUg/mL) were in some cases equal to or even higher than those of the respective reference drugs chloramphenicol (MIC=16- 64 MUg/mL) and nystatin (MIC=128-256 MUg/mL). PMID- 26352202 TI - Membrane Transport and Communication in Frankfurt: Speakers' Summary - Highlights. PMID- 26352203 TI - Structure, function, evolution, and application of bacterial Pnu-type vitamin transporters. AB - Many bacteria can take up vitamins from the environment via specific transport machineries. Uptake is essential for organisms that lack complete vitamin biosynthesis pathways, but even in the presence of biosynthesis routes uptake is likely preferred, because it is energetically less costly. Pnu transporters represent a class of membrane transporters for a diverse set of B-type vitamins. They were identified 30 years ago and catalyze transport by the mechanism of facilitated diffusion, without direct coupling to ATP hydrolysis or transport of coupling ions. Instead, directionality is achieved by metabolic trapping, in which the vitamin substrate is converted into a derivative that cannot be transported, for instance by phosphorylation. The recent crystal structure of the nicotinamide riboside transporter PnuC has provided the first insights in substrate recognition and selectivity. Here, we will summarize the current knowledge about the function, structure, and evolution of Pnu transporters. Additionally, we will highlight their role for potential biotechnological and pharmaceutical applications. PMID- 26352204 TI - Extending native mass spectrometry approaches to integral membrane proteins. AB - Recent developments in native mass spectrometry and ion mobility have made it possible to analyze the composition and structure of membrane protein complexes in the gas-phase. In this short review we discuss the experimental strategies that allow to elucidate aspects of the dynamic structure of these important drug targets, such as the structural effects of lipid binding or detection of co populated conformational and assembly states during gating on an ion channel. As native mass spectrometry relies on nano-electrospray of natively reconstituted proteins, a number of commonly used lipid- and detergent-based reconstitution systems have been evaluated for their compatibility with this approach, and parameters for the release of intact, native-like folded membrane proteins studied in the gas-phase. The strategy thus developed can be employed for the investigation of the subunit composition and stoichiometry, oligomeric state, conformational changes, and lipid and drug binding of integral membrane proteins. PMID- 26352205 TI - Corrigendum to: Performance criteria and quality indicators for the pre analytical phase. PMID- 26352207 TI - Difference in Outcomes of Rectal Foreign Bodies between Males and Females: A Retrospective Analysis of a National Inpatient Database in Japan. AB - BACKGROUND/AIMS: Almost all previous studies related to rectal foreign bodies were based on bizarre and striking cases, resulting in a reporting bias. Our aim was to clarify the clinico-epidemiological findings of rectal foreign body (RFB) in a general population. METHODS: Using a national administrative database in Japan, we identified patients who underwent in-hospital treatment for rectal foreign bodies from 1 July 2007 to 31 March 2013. RESULTS: A total of 648 RFB patients with 666 presentations were identified during the study period. The number of male patients was 526 (81.1%). The incidence of a RFB was most frequently seen in males who were in their 60s and in females who were in their 80s. The overall in-hospital mortality was 1.2%. Compared with males, females had a significantly higher proportion of in-hospital death (0.4 vs. 4.8%, p = 0.001), perforation and peritonitis (5.2 vs. 12.8%, p = 0.004), and sepsis (1.1 vs. 4.0%, p = 0.04). CONCLUSION: This study showed the clinico-epidemiological findings of rectal foreign bodies in a general population, and established that there was a low mortality rate. It was also found that females were significantly more likely to have a severe outcome following a RFB than males. PMID- 26352208 TI - Direct Visualization of Etching Trajectories in Metal-Assisted Chemical Etching of Si by the Chemical Oxidation of Porous Sidewalls. AB - We demonstrate a simple method for the visualization of trajectories traced by noble metal nanoparticles during metal-assisted chemical etching (MaCE) of Si. The nanoporous Si layer formed around drilled pores is converted into SiO2 by simple chemical oxidation. Etch removal of the remaining Si using alkali hydroxide leaves SiO2 nanostructures that are the exact replica of those drilled pores or etching trajectories. The differences in etching characteristics between Ag and Au have been investigated using the proposed visualization method. The shape and chemical stability of metal nanoparticles used for MaCE have been found to be critical in determining etching paths. The proposed method would be very helpful in studying the fundamental mechanism of MaCE as well as in micro/nanostructuring of the Si surface for various applications. This approach can also be used for the generation of straight or helical SiO2 nanotubes. PMID- 26352206 TI - Nicotinamide ameliorates palmitate-induced ER stress in hepatocytes via cAMP/PKA/CREB pathway-dependent Sirt1 upregulation. AB - Nicotinamide (NAM) is the amide of nicotinic acid and a predominant precursor for NAD(+) biosynthesis via the salvage pathway. Sirt1 is a NAD(+)-dependent deacetylase, playing an important role in regulating cellular functions. Although hepatoprotective effect of NAM has been reported, the underlying mechanism remains elusive. ER stress, induced by saturated fatty acids, in specific palmitate, plays a pathological role in the development of nonalcoholic fatty liver disease. This study aims to determine the effect of NAM on palmitate induced ER stress in hepatocytes and to elucidate molecular mechanisms behind. Both HepG2 cells and primary mouse hepatocytes were exposed to palmitate (conjugated to BSA at a 2:1 M ratio), NAM, or their combination for different durations. Cellular NAD(+) level, Sirt1 expression/activity, ER stress, as well as cAMP/PKA/CREB pathway activation were determined. NAM increased Sirt1 expression and enzymatic activity, which contributes to the ameliorative effect of NAM on palmitate-triggered ER stress. NAM increased intracellular NAD(+) level in hepatocytes, however, blocking the salvage pathway, a pathway for NAD(+) synthesis from NAM, only partially prevented NAM-induced Sirt1 upregulation while completely prevented NAD+ increase in response to NAM. Further mechanistic investigations revealed that NAM elevated intracellular cAMP level via suppressing PDE activity, leading to downstream PKA and CREB activation. Importantly, cAMP/PKA/CREB pathway blockade abolished not only NAM-induced Sirt1 upregulation, but also its protective effect against ER stress. Our results demonstrate that NAM protects hepatocytes against palmitate-induced ER stress in hepatocytes via upregulating Sirt1. Activation of the cAMP/PKA/CREB pathway plays a key role in NAM-induced Sirt1 upregulation. PMID- 26352209 TI - Visual Acuity Improvement of Amblyopia in an Adult With Levodopa/Carbidopa Treatment. AB - Amblyopia is the leading cause of visual loss in children, affecting 2% to 3% of the population. Occlusion of the dominant eye is the primary and best treatment, although efficacy decreases after 6 years of age. As a result, levodopa/carbidopa has been explored as an adjunct to conventional therapy and has been shown to have an immediate impact on visual acuity. Several studies to date have shown mixed results on the benefit of supplementing occlusion therapy with levodopa/carbidopa, although they have primarily studied children. The authors describe the oldest patient (46 years old) documented in the literature to have shown improvement in visual acuity using levodopa/carbidopa. He was given a 16 week course at a dose in line with previous studies while being effectively occluded full time due to a glaucomatous right eye with no light perception. On 3 month follow-up, his left eye improved two lines and stabilized at 6 months. PMID- 26352212 TI - Porous Silicon Nanotube Arrays as Anode Material for Li-Ion Batteries. AB - We report the electrochemical performance of Si nanotube vertical arrays possessing thin porous sidewalls for Li-ion batteries. Porous Si nanotubes were fabricated on stainless steel substrates using a sacrificial ZnO nanowire template method. These porous Si nanotubes are stable at multiple C-rates. A second discharge capacity of 3095 mAh g(-1) with a Coulombic efficiency of 63% is attained at a rate of C/20 and a stable gravimetric capacity of 1670 mAh g(-1) obtained after 30 cycles. The high capacity values are attributed to the large surface area offered by the porosity of the 3D nanostructures, thereby promoting lithium-ion storage according to a pseudocapacitive mechanism. PMID- 26352211 TI - Activity-Independent Discovery of Secondary Metabolites Using Chemical Elicitation and Cheminformatic Inference. AB - Most existing antibiotics were discovered through screens of environmental microbes, particularly the streptomycetes, for the capacity to prevent the growth of pathogenic bacteria. This "activity-guided screening" method has been largely abandoned because it repeatedly rediscovers those compounds that are highly expressed during laboratory culture. Most of these metabolites have already been biochemically characterized. However, the sequencing of streptomycete genomes has revealed a large number of "cryptic" secondary metabolic genes that are either poorly expressed in the laboratory or that have biological activities that cannot be discovered through standard activity-guided screens. Methods that reveal these uncharacterized compounds, particularly methods that are not biased in favor of the highly expressed metabolites, would provide direct access to a large number of potentially useful biologically active small molecules. To address this need, we have devised a discovery method in which a chemical elicitor called Cl-ARC is used to elevate the expression of cryptic biosynthetic genes. We show that the resulting change in product yield permits the direct discovery of secondary metabolites without requiring knowledge of their biological activity. We used this approach to identify three rare secondary metabolites and find that two of them target eukaryotic cells and not bacterial cells. In parallel, we report the first paired use of cheminformatic inference and chemical genetic epistasis in yeast to identify the target. In this way, we demonstrate that oxohygrolidin, one of the eukaryote-active compounds we identified through activity-independent screening, targets the V1 ATPase in yeast and human cells and secondarily HSP90. PMID- 26352213 TI - Study of novel molecular probe 99mTc-3PRGD2 in the diagnosis of rheumatoid arthritis. AB - INTRODUCTION: Angiogenesis in the synovial membrane plays an important role in the pathogenesis of rheumatoid arthritis (RA). Radiolabeled RGD (Arg-Gly-Asp) peptides can be used as a molecular probe in radionuclide imaging to assess angiogenesis noninvasively in vitro and investigate the process of RA to achieve the goal of early diagnosis and monitoring. The main objective of this study is to evaluate the value of RGD peptides conjugate with Tc-radiolabeled, Tc(HYNIC 3PRGD2)(tricine) (TPPTS) (Tc-3PRGD2 in short) in the diagnosis of RA. MATERIALS AND METHODS: Tc-3PRGD2 was synthesized using an HYNIC-3PRGD2 lyophilized kit with TcO4 labeling. Biodistribution and planar imaging studies were carried out in an RA rat model. The ankles were marked by arthritis index (AI) scores (from 0-3 score) according to the degree of ankle swelling and the ankle uptake of Tc 3PRGD2 was compared. Immunohistochemical staining was used to test the expression of integrin alphavbeta3 in the ankle tissue, analyzing the correlation between uptake of Tc-3PRGD2 and receptor expression. RESULTS: Planar imaging of arthritic ankles became visible at 30 min postinjection of Tc-3PRGD2 and was still clear at 6 h postinjection. The AI score increased, along with the uptake of Tc-3PRGD2. A biodistribution study showed that Tc-3PRGD2 was excreted by the urinary system. The uptake by ankles with different AI scores was 0.64+/-0.07%ID/g (0 score), 1.10+/-0.07%ID/g (1 score), 1.30+/-0.04%ID/g (2 score), and 1.73+/-0.05%ID/g (3 score), respectively, at 1 h postinjection, suggesting that the ankle uptake increased with an increase in the AI score. There was a linear positive correlation relationship (r=0.852, P<0.05) between the ankle uptake of Tc-3PRGD2 and the integrin alphavbeta3 expression levels in immunohistochemical study. CONCLUSION: Tc-3PRGD2 is a promising radiotracer for the diagnosis of RA. PMID- 26352214 TI - Assessment of the performance of small field of view gamma cameras for sentinel node imaging. AB - OBJECTIVE: To develop a method for the assessment of small field of view (SFOV) gamma cameras using a novel phantom designed to simulate the localization of sentinel nodes in the presence of a high-activity injection site. MATERIALS AND METHODS: The phantom consisted of a cube-shaped acrylic glass support frame. Sixteen acrylic glass plates and nine bars were stacked within the frame to allow a variable configuration of the simulated node depth and node-to-injection site separation. Syringes filled with Tc were used to simulate activity at the injection site and node. Scintigraphic imaging was carried out and the images were assessed subjectively and quantitatively through calculation of the contrast to-noise ratio. The detection performance of an SFOV gamma camera was then compared with that of a large field of view gamma camera. RESULTS: The detectability studies showed that the SFOV gamma camera could detect low activity in nodes by visual examination of images and with contrast-to-noise ratios ranging from 3 to 62. In particular, the phantom showed the limits of node detection using an SFOV gamma camera over activity ratios less than 1 : 100 and at depths below 45 mm with 25 mm of node-to-injection site separation. Visual subjective assessment of images acquired under the same conditions showed that the SFOV gamma camera was superior to a large field of view camera for the detection of nodes at a node-to-injection site separation of 25 mm. CONCLUSION: A low-cost phantom has been designed and fabricated that provides a versatile method for the assessment of SFOV gamma cameras intended for sentinel node imaging. PMID- 26352215 TI - Asymmetric [3 + 2] Cycloaddition of Methyleneindolinones with N,N'-Cyclic Azomethine Imines Catalyzed by a N,N'-Dioxide-Mg(OTf)2 Complex. AB - A highly efficient chiral N,N'-dioxide-Mg(OTf)2 catalyst system has been developed for the asymmetric 1,3-dipolar cycloaddition between methyleneindolinones and N,N'-cyclic azomethine imines. The desired pyrazolidine products with contiguous quaternary-tertiary stereocenters were obtained in up to 99% yields with up to 99% ee and >19:1 dr under mild reaction conditions. PMID- 26352216 TI - Oestrogen reporter transgenic medaka for non-invasive evaluation of aromatase activity. AB - Vertebrate reproduction involves complex steroid hormone interplay and inter conversion. A critical element in maintaining sex steroid levels is the enzyme aromatase (cytochrome P450 19A1) which converts androgens to oestrogens. In turn oestrogen signalling is targeted by numerous chemicals, from pharmaceuticals to agricultural chemicals, both frequent sources of contamination in waste waters and consequently rivers. Although many models are now available to address disruption of oestrogen signalling, there are currently no published protocols allowing discrimination between alterations in testosterone metabolism and in oestrogenic signalling. It was with this limitation in mind that we optimised this protocol. We show using a 48h protocol that pre-feeding fry of the choriogenin h-gfp (chgh-gfp) medaka line are sensitive to 0.05nM EE2 (15ng/L), within the range of the lowest published observable physiological effect concentrations for medaka. In addition, co-treatment with testosterone can reveal potential effects of test substances on aromatase enzymatic activity. As the measurements are visualised in real-time without affecting embryo viability, repeated measures are possible. We demonstrate the ability of this model to detect oestrogen receptor agonists, aromatisable androgens, P450 aromatase activity modulators and selective oestrogen response modulators. Importantly, the range of this assay is physiologically relevant. PMID- 26352217 TI - Cetuximab in combination with chemoradiotherapy in the treatment of recurrent and/or metastatic nasopharyngeal carcinoma. AB - The aim of the study was to assess the efficacy and toxicity of cetuximab in the combined treatment for patients with recurrent and/or metastatic nasopharyngeal carcinoma (R/M NPC). Between March 2007 and November 2011, a total of 30 R/M NPC patients treated with comprehensive therapy including cetuximab were retrospectively enrolled. Intensity-modulated radiation therapy was delivered in recurrent disease with a median dose of 60 Gy. Chemotherapy regimens included TP/TPF (docetaxel 60-75 mg/m d1+DDP 25 mg/m d1-3+/-5-FU 500 mg/m/day with 120-h infusion), GP (gemcitabine 1.0 g/m d1, d8+DDP 25 mg/m d1-3), and PC (paclitaxel 60 mg/m/week d1+carboplatin AUC 2/week d1). Acute and late toxicities were documented by the radiation oncologists. The median age of the patients was 44 years (range 26-62). A total of 21 patients (70%) achieved response (CR+PR). The median survival time, time to progression, and 2-year overall survival were 23.6, 12.2 months, and 53.3%, respectively. Cetuximab appears to be effective and well tolerated when combined with chemoradiation therapy for the treatment of R/M NPC. PMID- 26352218 TI - Long-term survival in small-cell carcinoma of the endometrium with liver and brain metastases. AB - Small-cell carcinoma (SmCC) of the endometrium is an extremely rare cancer and has a poor prognosis. Because long-term survival is rare, there is a paucity of data on the advanced disease stages. Thus, a standard treatment has not been established. We describe an extremely rare case of long-term survival in SmCC of the endometrium with liver and brain metastases. We provided multidisciplinary treatment, including brain surgery, subsequent whole-brain radiotherapy, gynecologic surgery, and adjuvant chemotherapy (irinotecan hydrochloride+cisplatin). The patient was treated successfully and has survived for more than 12 years with no evidence of the disease. Irinotecan hydrochloride+cisplatin chemotherapy was effective for controlling the liver metastases, and the resection of brain metastases and radiotherapy were effective for the treatment of brain metastases in our case. We reviewed the pertinent literature of advanced SmCC of the endometrium. PMID- 26352219 TI - Challenges in the implementation of trastuzumab biosimilars: an expert panel's recommendations. AB - Trastuzumab has transformed the treatment of HER2-positive breast cancer. Because of impending European patent expiry in 2017, numerous trastuzumab biosimilars are currently undergoing comparability exercises for marketing authorization. Although biosimilar products have been approved in Europe since 2006, many obstacles are expected for trastuzumab, resulting from its nature as a monoclonal antibody, its impact on overall survival, and its extensive biochemical complexities. Unsolved questions need to be addressed for the evaluation of biosimilars' activity in terms of appropriate clinical endpoint definitions for such anticancer drugs, specific assessment pathways and comparative testing of biosimilars, untested ensuing de facto combination of trastuzumab biosimilars with cytotoxics, and immunogenicity monitoring among immunocompromised patients. In such a context of uncertainties, the recent approval by the French parliament of biosimilar substitution, which would allow dispensing trastuzumab biosimilars in place of the originator, should interrogate the oncological community. A think tank of experts was created to delineate specificities and challenges stemming from trastuzumab biosimilars. PMID- 26352220 TI - MicroRNA-128 suppresses cell growth and metastasis in colorectal carcinoma by targeting IRS1. AB - Evidence has shown that microRNAs play important roles in tumor development, progression, and metastasis. miR-128 has been reported to be deregulated in different tumor types, whereas the function of miR-128 in colorectal carcinoma (CRC) largely remains to be elucidated. The aim of the present study was to investigate the clinical significance, biological effects and underlying mechanisms of miR-128 in CRC using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting. It was found that the expression of miR-128 was downregulated in CRC tissues and cell lines as determined by RT qPCR. Furthermore, the expression of miR-128 in tumor tissues was significantly negatively correlated with TNM stage and lymph node metastasis in CRC patients. Functional assay revealed that the overexpression of miR-128 inhibited CRC cell proliferation, colony formation, migration and invasion and promoted apoptosis in vitro, and suppressed CRC xenograft tumor growth in vivo. In addition, insulin receptor substrate 1 (IRS1), a key mediator in oncogenic insulin-like growth factor (IGF) signaling, was confirmed as a direct target of miR-128 by a luciferase reporter assay. Western blot analysis indicated that the overexpression of miR-128 significantly downregulated IRS1 expression and its downstream Akt signaling in CRC cells. Moreover, miR-128 was negatively associated with IRS1 in CRC tissues compared to adjacent non-tumor tissues. Taken together, these data suggested that miR-128 serves as a tumor suppressor and blocks CRC growth and metastasis by targeting IRS1. PMID- 26352222 TI - A Comprehensive Review of Treatment Options for Premenstrual Syndrome and Premenstrual Dysphoric Disorder. AB - Premenstrual dysphoric disorder (PMDD) is a severe form of premenstrual syndrome that involves a combination of emotional and physical symptoms that result in significant functional impairment. Because of the debilitating nature of PMDD, multiple treatment options have been considered. This review provides a comprehensive overview of these therapeutic regimens to help health care professionals provide adequate treatment for PMDD and premenstrual syndrome. The treatments that are reviewed are organized into the following categories: psychiatric, anovulatory, supplements, herbal, nonpharmacological, and other. Selective serotonin reuptake inhibitors have been established as the first-line treatment for PMDD. Although luteal phase or continuous dosing can be used, additional research is needed to more thoroughly compare the efficacies and differential symptom response of continuous, semi-intermittent, luteal phase, and symptoms-onset dosing. The psychiatric medications venlafaxine, duloxetine, alprazolam, and buspirone have also been found to be useful treatments for PMDD. Various anovulatory-related treatments have demonstrated efficacy; however, the use of some of these treatments remains limited due to potential side effects and/or the availability of cheaper alternatives. Although a variety of supplement and herbal-related treatments have been proposed, with some warranting further research, at this time only calcium supplementation has demonstrated a consistent therapeutic benefit. In conclusion, serotoninergic antidepressants have been established as the first-line treatment option for PMDD; however, there are a variety of additional treatment options that should be considered if a patient fails to achieve an adequate therapeutic response with a selective serotonin reuptake inhibitor. PMID- 26352221 TI - Acceptance-based Behavior Therapy for Depression With Psychosis: Results From a Pilot Feasibility Randomized Controlled Trial. AB - Acceptance-based depression and psychosis therapy (ADAPT), a mindfulness/acceptance-based behavioral activation treatment, showed clinically significant effects in the treatment of depression with psychosis in a previous open trial. The goal of the current study was to further test the feasibility of ADAPT to determine the utility of testing it in a future clinical trial, following a stage model of treatment development. Feasibility was determined by randomizing a small number of patients (N=13) with comorbid depression and psychosis to medication treatment as usual plus enhanced assessment and monitoring versus ADAPT for 4 months of outpatient treatment. Both conditions were deemed acceptable by patients. Differences in between-subjects effect sizes favored ADAPT posttreatment and were in the medium to large range for depression, psychosocial functioning, and experiential avoidance (ie, the target mechanism). Thus ADAPT shows promise for improving outcomes compared with medications alone and requires testing in a fully powered randomized trial. PMID- 26352223 TI - Avoiding Dual Agency in Clinical and Medicolegal Practice. AB - Mental health professionals who provide medicolegal services need to be aware of the very important differences between clinical and retained expert/forensic roles. This column offers a distinction between clinical and forensic roles in terms of responsibilities, objectives, and guiding ethical principles. Existing professional guidelines and other views from the medical literature that discourage the mixing of such roles are reviewed. The conflation of clinical and forensic roles and the attendant risks are considered, in terms of both competing interests and the possible ethical threat associated with assuming a dual role. Knowingly or unwittingly assuming a dual role is potentially harmful to the therapeutic alliance, threatens the expert's objectivity, and may jeopardize a patient's legal case. Guidance is offered as to how to avoid conflating clinical and forensic roles when compelled to provide medicolegal services. PMID- 26352224 TI - Family-centered Care in the Outpatient General Psychiatry Clinic. AB - Although family research supports family-centered care for all medical specialties, the benefit of family-centered care has not been fully realized in outpatient practice. Physicians, including psychiatrists, are not routinely taught how to work with families and may not be aware of the evidence-base for family interventions. However, some medical specialties, such as family medicine and palliative care, have a clinical practice that routinely includes the family. Clinicians working in medical clinics, such as diabetes clinics, know that successful management of chronic illness requires family involvement. Psychiatric clinics, such as The Family Center for Bipolar Disorder at Beth Israel Medical Center in New York City, also have a family-centered practice and show improved patient outcomes. This article provides guidelines, including clinical interview questions, to help psychiatrists practice family-centered care, either in a private office or in a general psychiatric outpatient clinic. The guidelines include questions that identify when to seek an in-depth family assessment or consultation. Family-centered care will become more useful when health care reimbursement focuses on patient outcome. PMID- 26352225 TI - Differential distribution of U6 (RNU6-1) expression in human carcinoma tissues demonstrates the requirement for caution in the internal control gene selection for microRNA quantification. AB - Alterations in microRNA (miRNA) expression patterns have been associated with a number of human diseases. Accurate quantitation of miRNA levels is important for their use as biomarkers and in determining their functions. Although the issue of proper miRNA detection was solved with the introduction of standard reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assays, numerous issues with the selection of appropriate internal control genes remain. U6 (RNU6 1) snRNA, the most commonly used internal control gene in miRNA RT-qPCR assays, was shown to be unstable in clinical samples, particularly cancer tissues. Identification of the distribution of U6 in different tissues is the premise of more accurate quantification of miRNAs. However, the distribution of U6 in human carcinoma tissues and corresponding normal tissues is unknown. In the present study, U6 levels were significantly higher in human breast carcinoma tissues compared with the corresponding normal tissues by RT-qPCR. In the carcinoma or corresponding adjacent normal tissues, the expression levels of U6 in epithelial cells were higher than those in the mesenchymal cells. Furthermore, the expression levels of U6 in the carcinoma tissues of the liver and intrahepatic bile ducts were higher than those in the adjacent normal tissues. These results suggest that the expression and distribution of U6 exhibits a high degree of variability among several types of human cells. Therefore, caution is required when selecting U6 as an internal control gene for evaluating expression profiles of miRNAs in patients with carcinoma, particularly carcinoma of the liver and intrahepatic bile ducts. PMID- 26352226 TI - Bayesian Estimation of the von-Mises Fisher Mixture Model with Variational Inference. AB - This paper addresses the Bayesian estimation of the von-Mises Fisher (vMF) mixture model with variational inference (VI). The learning task in VI consists of optimization of the variational posterior distribution. However, the exact solution by VI does not lead to an analytically tractable solution due to the evaluation of intractable moments involving functional forms of the Bessel function in their arguments. To derive a closed-form solution, we further lower bound the evidence lower bound where the bound is tight at one point in the parameter distribution. While having the value of the bound guaranteed to increase during maximization, we derive an analytically tractable approximation to the posterior distribution which has the same functional form as the assigned prior distribution. The proposed algorithm requires no iterative numerical calculation in the re-estimation procedure, and it can potentially determine the model complexity and avoid the over-fitting problem associated with conventional approaches based on the expectation maximization. Moreover, we derive an analytically tractable approximation to the predictive density of the Bayesian mixture model of vMF distributions. The performance of the proposed approach is verified by experiments with both synthetic and real data. PMID- 26352227 TI - Combining Structure and Parameter Adaptation of HMMs for Printed Text Recognition. AB - We present two algorithms that extend existing HMM parameter adaptation algorithms (MAP and MLLR) by adapting the HMM structure. This improvement relies on a smart combination of MAP and MLLR with a structure optimization procedure. Our algorithms are semi-supervised: to adapt a given HMM model on new data, they require little labeled data for parameter adaptation and a moderate amount of unlabeled data to estimate the criteria used for HMM structure optimization. Structure optimization is based on state splitting and state merging operations and proceeds so as to optimize either the likelihood or a heuristic criterion. Our algorithms are successfully applied to the recognition of printed characters by adapting the HMM character models of a polyfont printed text recognizer to new fonts. Our experiments involve a total of 1,120,000 real and 3,100,000 synthetic character images and concern a set of 89 HMM models. A comparison of our results with those of state-of-the-art adaptation algorithms (MAP and MLLR) shows a significant increase in the accuracy of character recognition. PMID- 26352228 TI - Dense 3D Reconstruction from High Frame-Rate Video Using a Static Grid Pattern. AB - Dense 3D reconstruction of fast moving objects could contribute to various applications such as body structure analysis, accident avoidance, and so on. In this paper, we propose a technique based on a one-shot scanning method, which reconstructs 3D shapes for each frame of a high frame-rate video capturing the scenes projected by a static pattern. To avoid instability of image processing, we restrict the number of colors used in the pattern to less than two. The proposed technique comprises (1) an efficient algorithm to eliminate ambiguity of projected parallel-line patterns by using intersection points, (2) a batch reconstruction algorithm of multiple frames by using spatio-temporal constraints, and (3) an efficient detection method of color-encoded grid pattern based on de Bruijn sequence. In the experiments, the line detection algorithm worked effectively and the dense reconstruction algorithm produces accurate and robust results. We also show the improved results by using temporal constraints. Finally, the dense reconstructions of fast moving objects in a high frame-rate video are presented. PMID- 26352229 TI - Fast Orthogonal Haar Transform Pattern Matching via Image Square Sum. AB - Although using image strip sum, an orthogonal Haar transform (OHT) pattern matching algorithm may have good performance, it requires three subtractions to calculate each Haar projection value on the sliding windows. By establishing a solid mathematical foundation for OHT, this paper based on the concept of image square sum, proposes a novel fast orthogonal Haar transform (FOHT) pattern matching algorithm, from which a Haar projection value can be obtained by only one subtraction. Thus, higher speed-ups can be achieved, while producing the same results with the full search pattern matching. A large number of experiments show that the speed-ups of FOHT are very competitive with OHT in most cases of matching one single pattern, and generally higher than OHT in all cases of matching multiple patterns, exceeding other high-level full search equivalent algorithms. PMID- 26352230 TI - Image Segmentation Using Higher-Order Correlation Clustering. AB - In this paper, a hypergraph-based image segmentation framework is formulated in a supervised manner for many high-level computer vision tasks. To consider short- and long-range dependency among various regions of an image and also to incorporate wider selection of features, a higher-order correlation clustering (HO-CC) is incorporated in the framework. Correlation clustering (CC), which is a graph-partitioning algorithm, was recently shown to be effective in a number of applications such as natural language processing, document clustering, and image segmentation. It derives its partitioning result from a pairwise graph by optimizing a global objective function such that it simultaneously maximizes both intra-cluster similarity and inter-cluster dissimilarity. In the HO-CC, the pairwise graph which is used in the CC is generalized to a hypergraph which can alleviate local boundary ambiguities that can occur in the CC. Fast inference is possible by linear programming relaxation, and effective parameter learning by structured support vector machine is also possible by incorporating a decomposable structured loss function. Experimental results on various data sets show that the proposed HO-CC outperforms other state-of-the-art image segmentation algorithms. The HO-CC framework is therefore an efficient and flexible image segmentation framework. PMID- 26352231 TI - Interactive Phrases: Semantic Descriptions for Human Interaction Recognition. AB - This paper addresses the problem of recognizing human interactions from videos. We propose a novel approach that recognizes human interactions by the learned high-level descriptions, interactive phrases. Interactive phrases describe motion relationships between interacting people. These phrases naturally exploit human knowledge and allow us to construct a more descriptive model for recognizing human interactions. We propose a discriminative model to encode interactive phrases based on the latent SVM formulation. Interactive phrases are treated as latent variables and are used as mid-level features. To complement manually specified interactive phrases, we also discover data-driven phrases from data in order to find potentially useful and discriminative phrases for differentiating human interactions. An information-theoretic approach is employed to learn the data-driven phrases. The interdependencies between interactive phrases are explicitly captured in the model to deal with motion ambiguity and partial occlusion in the interactions. We evaluate our method on the BIT-Interaction data set, UT-Interaction data set, and Collective Activity data set. Experimental results show that our approach achieves superior performance over previous approaches. PMID- 26352232 TI - Knowledge Adaptation with Partially Shared Features for Event Detection Using Few Exemplars. AB - Multimedia event detection (MED) is an emerging area of research. Previous work mainly focuses on simple event detection in sports and news videos, or abnormality detection in surveillance videos. In contrast, we focus on detecting more complicated and generic events that gain more users' interest, and we explore an effective solution for MED. Moreover, our solution only uses few positive examples since precisely labeled multimedia content is scarce in the real world. As the information from these few positive examples is limited, we propose using knowledge adaptation to facilitate event detection. Different from the state of the art, our algorithm is able to adapt knowledge from another source for MED even if the features of the source and the target are partially different, but overlapping. Avoiding the requirement that the two domains are consistent in feature types is desirable as data collection platforms change or augment their capabilities and we should be able to respond to this with little or no effort. We perform extensive experiments on real-world multimedia archives consisting of several challenging events. The results show that our approach outperforms several other state-of-the-art detection algorithms. PMID- 26352233 TI - Occlusion Reasoning for Object Detection under Arbitrary Viewpoint. AB - We present a unified occlusion model for object instance detection under arbitrary viewpoint. Whereas previous approaches primarily modeled local coherency of occlusions or attempted to learn the structure of occlusions from data, we propose to explicitly model occlusions by reasoning about 3D interactions of objects. Our approach accurately represents occlusions under arbitrary viewpoint without requiring additional training data, which can often be difficult to obtain. We validate our model by incorporating occlusion reasoning with the state-of-the-art LINE2D and Gradient Network methods for object instance detection and demonstrate significant improvement in recognizing texture-less objects under severe occlusions. PMID- 26352234 TI - Photometric Stereo Using Sparse Bayesian Regression for General Diffuse Surfaces. AB - Most conventional algorithms for non-Lambertian photometric stereo can be partitioned into two categories. The first category is built upon stable outlier rejection techniques while assuming a dense Lambertian structure for the inliers, and thus performance degrades when general diffuse regions are present. The second utilizes complex reflectance representations and non-linear optimization over pixels to handle non-Lambertian surfaces, but does not explicitly account for shadows or other forms of corrupting outliers. In this paper, we present a purely pixel-wise photometric stereo method that stably and efficiently handles various non-Lambertian effects by assuming that appearances can be decomposed into a sparse, non-diffuse component (e.g., shadows, specularities, etc.) and a diffuse component represented by a monotonic function of the surface normal and lighting dot-product. This function is constructed using a piecewise linear approximation to the inverse diffuse model, leading to closed-form estimates of the surface normals and model parameters in the absence of non-diffuse corruptions. The latter are modeled as latent variables embedded within a hierarchical Bayesian model such that we may accurately compute the unknown surface normals while simultaneously separating diffuse from non-diffuse components. Extensive evaluations are performed that show state-of-the-art performance using both synthetic and real-world images. PMID- 26352235 TI - Scale Space for Camera Invariant Features. AB - In this paper we propose a new approach to compute the scale space of any central projection system, such as catadioptric, fisheye or conventional cameras. Since these systems can be explained using a unified model, the single parameter that defines each type of system is used to automatically compute the corresponding Riemannian metric. This metric, is combined with the partial differential equations framework on manifolds, allows us to compute the Laplace-Beltrami (LB) operator, enabling the computation of the scale space of any central projection system. Scale space is essential for the intrinsic scale selection and neighborhood description in features like SIFT. We perform experiments with synthetic and real images to validate the generalization of our approach to any central projection system. We compare our approach with the best-existing methods showing competitive results in all type of cameras: catadioptric, fisheye, and perspective. PMID- 26352236 TI - Segmentation and Enhancement of Latent Fingerprints: A Coarse to Fine Ridge Structure Dictionary. AB - Latent fingerprint matching has played a critical role in identifying suspects and criminals. However, compared to rolled and plain fingerprint matching, latent identification accuracy is significantly lower due to complex background noise, poor ridge quality and overlapping structured noise in latent images. Accordingly, manual markup of various features (e.g., region of interest, singular points and minutiae) is typically necessary to extract reliable features from latents. To reduce this markup cost and to improve the consistency in feature markup, fully automatic and highly accurate ("lights-out" capability) latent matching algorithms are needed. In this paper, a dictionary-based approach is proposed for automatic latent segmentation and enhancement towards the goal of achieving "lights-out" latent identification systems. Given a latent fingerprint image, a total variation (TV) decomposition model with L1 fidelity regularization is used to remove piecewise-smooth background noise. The texture component image obtained from the decomposition of latent image is divided into overlapping patches. Ridge structure dictionary, which is learnt from a set of high quality ridge patches, is then used to restore ridge structure in these latent patches. The ridge quality of a patch, which is used for latent segmentation, is defined as the structural similarity between the patch and its reconstruction. Orientation and frequency fields, which are used for latent enhancement, are then extracted from the reconstructed patch. To balance robustness and accuracy, a coarse to fine strategy is proposed. Experimental results on two latent fingerprint databases (i.e., NIST SD27 and WVU DB) show that the proposed algorithm outperforms the state-of-the-art segmentation and enhancement algorithms and boosts the performance of a state-of-the-art commercial latent matcher. PMID- 26352238 TI - The Spike-and-Slab RBM and Extensions to Discrete and Sparse Data Distributions. AB - The spike-and-slab restricted Boltzmann machine (ssRBM) is defined to have both a real-valued "slab" variable and a binary "spike" variable associated with each unit in the hidden layer. The model uses its slab variables to model the conditional covariance of the observation-thought to be important in capturing the statistical properties of natural images. In this paper, we present the canonical ssRBM framework together with some extensions. These extensions highlight the flexibility of the spike-and-slab RBM as a platform for exploring more sophisticated probabilistic models of high dimensional data in general and natural image data in particular. Here, we introduce the subspace-ssRBM focused on the task of learning invariant features. We highlight the behaviour of the ssRBM and its extensions through experiments with the MNIST digit recognition task and the CIFAR-10 object classification task. PMID- 26352237 TI - The Hidden Sides of Names--Face Modeling with First Name Attributes. AB - This paper introduces the new idea of describing people using first names. We show that describing people in terms of similarity to a vector of possible first names is a powerful representation of facial appearance that can be used for a number of important applications, such as naming never-seen faces and building facial attribute classifiers. We build models for 100 common first names used in the US and for each pair, construct a pairwise first-name classifier. These classifiers are built using training images downloaded from the internet, with no additional user interaction. This gives our approach important advantages in building practical systems that do not require additional human intervention for data labeling. The classification scores from each pairwise name classifier can be used as a set of facial attributes to describe facial appearance. We show several surprising results. Our name attributes predict the correct first names of test faces at rates far greater than chance. The name attributes are applied to gender recognition and to age classification, outperforming state-of-the-art methods with all training images automatically gathered from the internet. We also demonstrate the powerful use of our name attributes for associating faces in images with names from caption, and the important application of unconstrained face verification. PMID- 26352239 TI - Direct Orthogonal Distance to Quadratic Surfaces in 3D. AB - Discovering the orthogonal distance to a quadratic surface is a classic geometric task in vision, modeling, and robotics. I describe a simple, efficient, and stable direct solution for the orthogonal distance (foot-point) to an arbitrary quadratic surface from a general finite 3D point. The problem is expressed as the intersection of three quadratic surfaces, two of which are derived from the requirement of orthogonality of two non-coincident planes with the tangent plane to the quadric. A sixth order single-variable polynomial is directly generated in one coordinate of the surface point. The method detects intersection points at infinity and operates smoothly across all real quadratic surface classes. The method also geometrically detects continuums of orthogonal points (i.e., from the exact center of a sphere). I discuss algorithm performance, compare it to a state of-the-art estimator, demonstrate the algorithm on synthetic data, and describe extension to arbitrary dimension. PMID- 26352240 TI - Efficient Energy Minimization for Enforcing Label Statistics. AB - Energy minimization algorithms, such as graph cuts, enable the computation of the MAP solution under certain probabilistic models such as Markov random fields. However, for many computer vision problems, the MAP solution under the model is not the ground truth solution. In many problem scenarios, the system has access to certain statistics of the ground truth. For instance, in image segmentation, the area and boundary length of the object may be known. In these cases, we want to estimate the most probable solution that is consistent with such statistics, i.e., satisfies certain equality or inequality constraints. The above constrained energy minimization problem is NP-hard in general, and is usually solved using Linear Programming formulations, which relax the integrality constraints. This paper proposes a novel method that directly finds the discrete approximate solution of such problems by maximizing the corresponding Lagrangian dual. This method can be applied to any constrained energy minimization problem whose unconstrained version is polynomial time solvable, and can handle multiple, equality or inequality, and linear or non-linear constraints. One important advantage of our method is the ability to handle second order constraints with both-side inequalities with a weak restriction, not trivial in the relaxation based methods, and show that the restriction does not affect the accuracy in our cases.We demonstrate the efficacy of our method on the foreground/background image segmentation problem, and show that it produces impressive segmentation results with less error, and runs more than 20 times faster than the state-of-the art LP relaxation based approaches. PMID- 26352241 TI - Low-Level Hierarchical Multiscale Segmentation Statistics of Natural Images. AB - This paper is aimed at obtaining the statistics as a probabilistic model pertaining to the geometric, topological and photometric structure of natural images. The image structure is represented by its segmentation graph derived from the low-level hierarchical multiscale image segmentation. We first estimate the statistics of a number of segmentation graph properties from a large number of images. Our estimates confirm some findings reported in the past work, as well as provide some new ones. We then obtain a Markov random field based model of the segmentation graph which subsumes the observed statistics. To demonstrate the value of the model and the statistics, we show how its use as a prior impacts three applications: image classification, semantic image segmentation and object detection. PMID- 26352242 TI - Ischaemic heart disease - a selected review of recent developments. AB - PURPOSE OF REVIEW: The purpose of this review is to highlight important and interesting advances in the field of ischaemic heart disease that have occurred over the last 18 months. It is focused on research that is likely to lead to changes in clinical practice. RECENT FINDINGS: There is new evidence on appropriate pharmacotherapy during angioplasty in both stable and unstable patients. The use of pressure wire assessment has been shown to improve patient outcome. The management of patients with ST elevation myocardial infarction (STEMI) is likely to change with a reduction in the use of manual thrombectomy and an increase in the treatment of nonculprit disease. SUMMARY: The optimal duration of dual antiplatelet therapy in percutaneous coronary intervention remains an intensely debated topic with contradictory results from major trials. Pressure wire guided coronary intervention reduces the need for urgent revascularization. The use of fractional flow reserve computed tomography has the potential to revolutionize functional testing. The treatment of patients presenting with ST elevation myocardial infarction is likely to change dramatically. Heparin with bailout glycoprotein IIbIIIa-inhibitor (GPIIbIIIa-I) appears superior to bivalirudin alone, although there is no longer a role for routine manual thrombectomy. Multivessel PCI to establish complete revascularization may become the gold standard in patients presenting with STEMI, although larger trials are needed. Novel therapies are being devised for the treatment of patients with intractable angina, but further work is required in this area. PMID- 26352244 TI - Off-pump coronary artery bypass: past, present and future of a controversial technology. AB - PURPOSE OF REVIEW: This review will examine the current role of off-pump coronary artery bypass (OPCAB) surgery compared with on-pump coronary artery bypass (ONCAB) surgery for the revascularization of ischemic myocardium. RECENT FINDINGS: Recent studies have confirmed earlier findings that OPCAB is associated with less grafts per patient and less complete revascularization, and increased incidence of recurrent angina and need for repeat revascularization procedures, and more frequent rehospitalization for cardiac-related issues. OPCAB does not prevent postoperative renal dysfunction and is associated with worse long-term outcomes. Hospital costs are not reduced and are increased in those OPCAB patients who require intraoperative conversion to ONCAB procedures; however, when multiple arterial grafts are used and a complete revascularization is performed, OPCAB outcomes are equivalent to those of ONCAB procedures. SUMMARY: OPCAB should only be performed by surgeons experienced in this technique in patients in whom a complete revascularization can be achieved; preferably with multiple arterial grafts. PMID- 26352243 TI - Abdominal aortic aneurysm: novel mechanisms and therapies. AB - PURPOSE OF REVIEW: Abdominal aortic aneurysm (AAA) is a pathological condition of permanent dilation that portends the potentially fatal consequence of aortic rupture. This review emphasizes recent advances in mechanistic insight into aneurysm pathogenesis and potential pharmacologic therapies that are on the horizon for AAAs. RECENT FINDINGS: An increasing body of evidence demonstrates that genetic factors, including 3p12.3, DAB2IP, LDLr, LRP1, matrix metalloproteinase (MMP)-3, TGFBR2, and SORT1 loci, are associated with AAA development. Current human studies and animal models have shown that many leukocytes and inflammatory mediators, such as IL-1, IL-17, TGF-beta, and angiotensin II, are involved in the pathogenesis of AAAs. Leukocytic infiltration into aortic media leads to smooth muscle cell depletion, generation of reactive oxygen species, and extracellular matrix fragmentation. Preclinical investigations into pharmacological therapies for AAAs have provided intriguing insight into the roles of microRNAs in regulating many pathological pathways in AAA development. Several large clinical trials are ongoing, seeking to translate preclinical findings into therapeutic options. SUMMARY: Recent studies have identified many potential mechanisms involved in AAA pathogenesis that provide insight into the development of a medical treatment for this disease. PMID- 26352245 TI - The temporal recovery of fractional flow reserve, coronary flow reserve and index of microcirculatory resistance following myocardial infarction. AB - PURPOSE OF REVIEW: The purpose of this review was to summarize the healing processes after myocardial infarction (MI) and to relate these temporal changes to data from serial imaging obtained by cardiac magnetic resonance, and then to relate these findings to the invasive measures of the indices of coronary physiology (e.g., fractional flow reserve, coronary flow reserve and index of microcirculatory resistance). RECENT FINDINGS: Indices of coronary physiology measured with an intracoronary wire represent an easily and readily available diagnostic tool for the management of coronary artery disease. Additionally, they give insight into the functional status of the coronary microvasculature. Recent evidence has confirmed initial observations that microvascular recovery occurs after MI and that this is reflected by a progressive improvement of all the indices of coronary physiology over time. More importantly, it has been clarified that this process is variable, but probably predictable as it is affected by the degree of microvascular injury occurring in the acute phase of MI. SUMMARY: Microvascular recovery after acute MI affects the measurement of the indices of coronary physiology. Use of fractional flow reserve, coronary flow reserve and index of microcirculatory resistance requires an understanding of how microvasculature evolves after MI. This understanding allows appropriate application of intracoronary physiology both clinically and in research settings. PMID- 26352246 TI - Coronary artery bypass grafting in octogenarians: only when percutaneous coronary intervention is not feasible? AB - PURPOSE OF REVIEW: The aim of this study was to review recent literature reporting the results of coronary revascularization by percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) in patients older than 80 years. RECENT FINDINGS: The review of recent studies on octogenarians demonstrates a surgical CABG advantage in the case of patients with increasing baseline coronary risk, such as severe multivessel disease, chronic total occlusions, and left ventricular dysfunction. PCI seems to be more appropriate for less severe degree and distribution of coronary lesions, and for subgroups of patients with higher surgical risk, such as acute coronary syndromes, reoperations, malignancy, dementia, poor mobility, frailty, and serious comorbidities contraindicating extracorporeal circulation. SUMMARY: It is not the case that CABG is indicated only when there are contraindications to PCI. CABG confers more benefit than PCI in patients with increasing baseline cardiac risk, in the absence of serious systemic diseases that can reasonably reduce their life expectancy.CABG and PCI, with proper selection, should be considered complementary rather than competitive procedures in the therapy of octogenarians affected by coronary artery disease. PMID- 26352247 TI - Operative mortality with coronary artery bypass graft: where do we stand in 2015? AB - PURPOSE OF REVIEW: Coronary artery bypass graft (CABG) surgery has evolved and become much safer since its inception. This article outlines recent strategies in optimizing CABG mortality. RECENT FINDINGS: Improving operative mortality around CABG relates to five components. These include the role of relevant quality indicators; improved CABG techniques, such as multiple arterial grafting with less manipulation of the aorta; improvements in cardiopulmonary bypass; refinements in cardiac anaesthesia along with postoperative care; and the development of centres of excellence. SUMMARY: The development of advanced surgical revascularization techniques raises the question as to whether CABG expertise should be considered a sub-specialty of cardiac surgery. An expert CABG surgeon should be able to appropriately utilize several different revascularization techniques to adjust the operation to the patient, rather than the contrary. PMID- 26352248 TI - Metabolic Changes Induced by Electrical Stimulation of Prelemniscal Radiations for the Treatment of Parkinson Disease. AB - OBJECTIVE: The aim of this work was to study mechanisms of action of electrical stimulation of prelemniscal radiations (Raprl) in the treatment of Parkinson disease, using 2-deoxy-2-fluoro-D-glucose (18F-FDG) Positron Emission Tomography (PET/CT). Materialand Methods: Five patients with PD and predominant unilateral tremor, rigidity and bradykinesia underwent deep brain stimulation (DBS) in contralateral Raprl that improved symptoms from 82.4 to 94.5%. 18F-FDG PET studies were performed before electrode implantation and after DBS therapy. Changes in metabolic activity in PET were evaluated by the maximal standardized uptake value (MSUV) and statistical parametric mapping (SPM) for regions of interest (ROIs) ipsilateral and contralateral to the stimulation site. ROIs were derived from a preoperative probabilistic tractography and included primary motor, supplementary motor and orbitofrontal cortices: Raprl, ventrolateral thalamus, putamen and cerebellum. RESULTS: No significant MSUV changes occurred in ROIs contralateral to Raprl-DBS. In contrast, MSUV decreased ipsilateral to DBS in Raprl, the thalamus, and the primary and supplementary motor cortices. SPM analysis showed metabolic changes which were significantly different after DBS therapy in all ROIs ipsilateral to DBS compared to those in the contralateral side. CONCLUSION: Raprl-DBS decreases the metabolic activity of areas anatomically related to its fiber composition. Improvement of symptoms may result from a decrease in pathological overactivity of circuits related to the ROIs. PMID- 26352249 TI - Electrochemical aptasensor of cardiac troponin I for the early diagnosis of acute myocardial infarction. AB - Cardiac troponin I (cTnI) is well-known as a promising biomarker for the early diagnosis of acute myocardial infarction (AMI). In this work, single-stranded DNA aptamers against cTnI were identified by the Systematic Evolution of Ligands by Exponential enrichment (SELEX) method. The aptamer candidates exhibited a high selectivity and sensitivity toward both cTnI and the cardiac Troponin complex. The binding affinities of each aptamer were evaluated based on their dissociation constants (Kd) by surface plasma resonance. The Tro4 aptamer that had the highest binding capacity to cTnI showed a very low Kd value (270 pM) compared with that of a cTnI antibody (20.8 nM). Furthermore, we designed a new electrochemical aptasensor based on square wave voltammetry using ferrocene-modified silica nanoparticles. The developed aptasensor demonstrated an excellent analytical performance for cTnI with a wide linear range of 1-10 000 pM in a buffer and a detection limit of 1.0 pM (24 pg/mL; S/N = 3), which was noticeably lower than the cutoff values (70-400 pg/mL). The specificity of the aptamers was also examined using nontarget proteins, demonstrating that the proposed sensor responded to only cTnI. In addition, cTnI was successfully detected in a human serum albumin solution. On the basis of the calibration curve that was constructed, the concentrations of cTnI in a solution supplemented with human serum were effectively measured. The calculated values correlated well with the actual concentrations of cTnI. It is anticipated that the highly sensitive and selective aptasensor for cTnI could be readily applicable for the accurate diagnosis of AMI. PMID- 26352251 TI - High-Resolution Anoscopy: A Valuable Skill for Colorectal Surgeons and Nurse Practitioners. PMID- 26352250 TI - Ambient Ammonia Exposures in an Agricultural Community and Pediatric Asthma Morbidity. AB - BACKGROUND: Large-scale animal feeding operations compromise regional air quality in the rural US through emission of pollutants, such as ammonia gas. Exposure to airborne pollution from animal feeding operations may cause pediatric asthma exacerbations in surrounding communities. OBJECTIVES: To describe spatial and temporal patterns in ambient ammonia concentrations in an agricultural region, and to investigate associations between short-term fluctuations in ammonia and subsequent changes in respiratory health in children with asthma. METHODS: For 13 months in the Yakima Valley of Washington State, 14 monitors sampled ammonia in outdoor air for 24-hour periods every 6 days. School-age children with asthma (n = 51) were followed for two health outcomes: biweekly reports of asthma symptoms and quick relief medication usage, and daily measurements of forced expiratory volume in 1 second. We assessed associations between each outcome and ammonia using generalized estimating equations. RESULTS: Twenty-four-hour ammonia concentrations varied from 0.2 to 238.1 MUg/m during the study period and displayed a strong correlation with proximity to animal feeding operations. The percentage of forced expiratory volume in 1 second was 3.8% lower (95% confidence interval = 0.2, 7.3) per interquartile increase in 1-day lagged ammonia concentration and 3.0% lower (95% confidence interval = 0.5, 5.8) for 2-day lagged concentration. We observed no associations between self-reported asthma symptoms or medication usage and estimated ammonia exposure. CONCLUSIONS: Ammonia concentrations were elevated in this community and strongly predicted by proximity to animal feeding operations. Ammonia's association with acute lung function decrements in children with asthma in the surrounding community may be causal or, alternatively, ammonia may be a marker for other pollutants from animal feeding operations associated with respiratory effects. PMID- 26352252 TI - Effect of Needle Size on Pain Perception in Patients Treated With Botulinum Toxin Type A Injections: A Randomized Clinical Trial. AB - IMPORTANCE: Transcutaneous injection through smaller hollow-bore needles may decrease patient discomfort, but current evidence is equivocal. OBJECTIVE: To compare injection discomfort in patients treated with botulinum toxin type A with 30- and 32-gauge needles. DESIGN, SETTING, AND PARTICIPANTS: Split-face, patient- and injector-blinded randomized clinical trial at the dermatology service of an urban university medical center. The 20 participants were women aged 25 to 70 years in good health and with moderate dynamic forehead and glabellar wrinkles. Data were collected from November 20, 2013, through January 16, 2014. Follow-up was complete on January 16, 2014. Data from the per-protocol population were analyzed from July 1 to July 31, 2014. INTERVENTIONS: One side of each patient'sforehead received botulinum toxin type A in saline injected with a 32 gauge needle; the other side received the same treatment injected with a 30-gauge needle. In addition, each patient received randomized injections of saline only to both upper inner arms with the same types of needles. MAIN OUTCOMES AND MEASURES: Primary outcomes included the patient-reported pain rating on a visual analog scale (VAS) on either side of the face and arms and the proportion of patients whose VAS ratings corresponded with more than moderate (ie, clinically significant) pain. The secondary outcome consisted of patient-reported information about the character of the pain at both sites using the expanded and revised version of the Short-Form McGill Pain Questionnaire. RESULTS: All 20 patients completed the study. Overall, facial and arm injections were nominally but not significantly more painful with 30-gauge needles (mean [SD] VAS ratings for the face, 4.16 [2.55] vs 3.41 [2.31], P = .34; for the arm, 1.66 [2.07] vs 1.21 [1.65], P = .45). For facial injections, the likelihood of clinically significant pain (VAS rating, >=5.4) was significantly greater with 30-gauge needles, which were associated with such pain in 8 patients (40%) compared with the 32-gauge needles, which were associated with such pain in 3 patients (15%) (odds ratio, 3.80 [95% CI, 1.05-13.78]; P = .04). No difference was found in the character of pain associated with needle bore (P > .05 for all comparisons). CONCLUSIONS AND RELEVANCE: For facial injections of neurotoxin in saline, 30 gauge needles were associated with greater incidence of clinically significant pain than 32-gauge needles. For patients prone to experience clinically significant pain with facial injections, use of 32-gauge needles may minimize this discomfort. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01981174. PMID- 26352253 TI - Enterotoxin-Encoding Genes in Staphylococcus spp. from Food Handlers in a University Restaurant. AB - Food handlers carrying enterotoxin-producing Staphylococcus are a potential source of food poisoning. The aim of this study was to analyze genes encoding enterotoxins in coagulase-positive Staphylococcus (CoPS) and coagulase-negative Staphylococcus (CoNS) isolated from the anterior nostrils and hands of food handlers at a university restaurant in the city of Natal, Northeast Brazil. Thirty food handlers were screened for the study. The isolates were subjected to Gram staining, a bacitracin sensitivity test, mannitol fermentation, and catalase and coagulase tests. CoNS and CoPS strains were subsequently identified by a Vitek 2 System (BioMerieux, France) and various biochemical tests. Polymerase chain reaction was used to detect genes for enterotoxins A, B, C, D, E, G, H, and I (sea, seb, sec, sed, see, seg, seh, and sei) and a disc-diffusion method was used to determine susceptibility to several classes of antimicrobials. All food handlers presented staphylococci on their hands and/or noses. The study found 58 Staphylococcus spp., of which 20.7% were CoPS and 79.3% were CoNS. S. epidermidis was the most prevalent species. Twenty-nine staphylococci (50%) were positive for one or more enterotoxin genes, and the most prevalent genes were seg and sei, each with a frequency of 29.3%. Indeed, CoNS encoded a high percentage of enterotoxin genes (43.5%). However, S. aureus encoded even more enterotoxin genes (75%). Most isolates showed sensitivity to the antibiotics used for testing, except for penicillin (only 35% sensitive). The results from this study reinforce that coagulase-negative as well as coagulase-positive staphylococci isolated from food handlers are capable of genotypic enterotoxigenicity. PMID- 26352254 TI - Lethal and Sublethal Effects of Ivermectin on Onthophagus landolti (Coleoptera: Scarabaeidae). AB - Previous work has documented toxic effects of ivermectin (IVM) on dung beetles from the Old World, but very little is known about this drug's effect on Neotropical dung beetles. Accordingly, we conducted a bioassay with dung spiked with IVM to assess its lethal and sublethal effects on the Neotropical dung beetle Onthophagus landolti Harold. The experimental design consisted of five treated groups G1, G2, G3, G4, and G5 receiving 0.001, 0.01, 0.1, 1.0, and 10 mg IVM/kg dung fresh weight, respectively, and two control groups (solvent control [CGA] and untreated control [CGU]). Adult survival and fecundity were measured throughout a 10-d period, and subsequent egg development and survival were monitored. Adult survival was only affected for treatment groups G4 and G5 groups (70 and 30%, respectively); groups G1, G2, G3 and both controls exhibited 100% survival. Fecundity was completely suppressed under treatment groups G4 and G5. Group G3 only had 1.7 and 2.1% brood mass production relative to CGA and CGU, respectively. Additionally, for groups G1 and G2 the proportion of adults emerging from brood masses was lower relative to CGA. Furthermore, development time for the second generation in groups G1 and G2 was 12.5% slower relative to control groups. Finally, dung removal by beetles from groups G3, G4, and G5 was significantly lower relative to control groups. In conclusion, toxic effects of IVM on O. landolti are associated mainly with reduced fecundity and lower dung removal by adult beetles as well as reduced survival and slower development of offspring. PMID- 26352255 TI - Value of Riparian Vegetation Remnants for Leaf-Litter Ants (Hymenoptera: Formicidae) in a Human-Dominated Landscape in Central Veracruz, Mexico. AB - Riparian remnants are linear strips of vegetation immediately adjacent to rivers that may act as refuges for biodiversity, depending on their habitat quality. In this study, we evaluated the role of riparian remnants in contributing to the diversity of leaf-litter ants by determining the relationship between ant diversity and several riparian habitat characteristics within a human-dominated landscape in Veracruz, Mexico. Sampling was carried out in 2012 during both dry and rainy seasons at 12 transects 100 m in length, where 10 leaf-litter samples were collected along each transect and processed with Berlese-Tullgren funnels and Winkler sacks. A total of 8,684 individuals belonging to 53 species, 22 genera, and seven subfamilies were collected. The observed mean alpha diversity accounted for 34.4% of the total species recorded and beta diversity for 65.6%. Species richness and composition were significantly related to litter-layer depth and soil compaction, which could limit the distribution of ant species depending on their nesting, feeding, and foraging habits. Riparian remnants can contribute toward the conservation of ant assemblages and likely other invertebrate communities that are threatened by anthropogenic pressures. In human-dominated landscapes where remnants of riparian vegetation give refuge to a diverse array of myrmecofauna, the protection of the few remaining and well-preserved riparian sites is essential for the long-term maintenance of biodiversity. PMID- 26352256 TI - The Antibacterial Activity of Acetic Acid against Biofilm-Producing Pathogens of Relevance to Burns Patients. AB - INTRODUCTION: Localised infections, and burn wound sepsis are key concerns in the treatment of burns patients, and prevention of colonisation largely relies on biocides. Acetic acid has been shown to have good antibacterial activity against various planktonic organisms, however data is limited on efficacy, and few studies have been performed on biofilms. OBJECTIVES: We sought to investigate the antibacterial activity of acetic acid against important burn wound colonising organisms growing planktonically and as biofilms. METHODS: Laboratory experiments were performed to test the ability of acetic acid to inhibit growth of pathogens, inhibit the formation of biofilms, and eradicate pre-formed biofilms. RESULTS: Twenty-nine isolates of common wound-infecting pathogens were tested. Acetic acid was antibacterial against planktonic growth, with an minimum inhibitory concentration of 0.16-0.31% for all isolates, and was also able to prevent formation of biofilms (at 0.31%). Eradication of mature biofilms was observed for all isolates after three hours of exposure. CONCLUSIONS: This study provides evidence that acetic acid can inhibit growth of key burn wound pathogens when used at very dilute concentrations. Owing to current concerns of the reducing efficacy of systemic antibiotics, this novel biocide application offers great promise as a cheap and effective measure to treat infections in burns patients. PMID- 26352257 TI - Effect of Educational Outreach Timing and Duration on Facility Performance for Infectious Disease Care in Uganda: A Trial with Pre-Post and Cluster Randomized Controlled Components. AB - BACKGROUND: Classroom-based learning is often insufficient to ensure high quality care and application of health care guidelines. Educational outreach is garnering attention as a supplemental method to enhance health care worker capacity, yet there is little information about the timing and duration required to improve facility performance. We sought to evaluate the effects of an infectious disease training program followed by either immediate or delayed on-site support (OSS), an educational outreach approach, on nine facility performance indicators for emergency triage, assessment, and treatment; malaria; and pneumonia. We also compared the effects of nine monthly OSS visits to extended OSS, with three additional visits over six months. METHODS: This study was conducted at 36 health facilities in Uganda, covering 1,275,960 outpatient visits over 23 months. From April 2010 to December 2010, 36 sites received infectious disease training; 18 randomly selected sites in arm A received nine monthly OSS visits (immediate OSS) and 18 sites in arm B did not. From March 2011 to September 2011, arm A sites received three additional visits every two months (extended OSS), while the arm B sites received eight monthly OSS visits (delayed OSS). We compared the combined effect of training and delayed OSS to training followed by immediate OSS to determine the effect of delaying OSS implementation by nine months. We also compared facility performance in arm A during the extended OSS to immediate OSS to examine the effect of additional, less frequent OSS. RESULTS: Delayed OSS, when combined with training, was associated with significant pre/post improvements in four indicators: outpatients triaged (44% vs. 87%, aRR = 1.54, 99% CI = 1.11, 2.15); emergency and priority patients admitted, detained, or referred (16% vs. 31%, aRR = 1.74, 99% CI = 1.10, 2.75); patients with a negative malaria test result prescribed an antimalarial (53% vs. 34%, aRR = 0.67, 99% CI = 0.55, 0.82); and pneumonia suspects assessed for pneumonia (6% vs. 27%, aRR = 2.97, 99% CI = 1.44, 6.17). Differences between the delayed OSS and immediate OSS arms were not statistically significant for any of the nine indicators (all adjusted relative RR (aRRR) between 0.76-1.44, all p>0.06). Extended OSS was associated with significant improvement in two indicators (outpatients triaged: aRR = 1.09, 99% CI = 1.01; emergency and priority patients admitted, detained, or referred: aRR = 1.22, 99% CI = 1.01, 1.38) and decline in one (pneumonia suspects assessed for pneumonia: aRR: 0.93; 99% CI = 0.88, 0.98). CONCLUSIONS: Educational outreach held up to nine months after training had similar effects on facility performance as educational outreach started within one month post-training. Six months of bi-monthly educational outreach maintained facility performance gains, but incremental improvements were heterogeneous. PMID- 26352258 TI - Nanoformulation of Geranylgeranyltransferase-I Inhibitors for Cancer Therapy: Liposomal Encapsulation and pH-Dependent Delivery to Cancer Cells. AB - Small molecule inhibitors against protein geranylgeranyltransferase-I such as P61A6 have been shown to inhibit proliferation of a variety of human cancer cells and exhibit antitumor activity in mouse models. Development of these inhibitors could be dramatically accelerated by conferring tumor targeting and controlled release capability. As a first step towards this goal, we have encapsulated P61A6 into a new type of liposomes that open and release cargos only under low pH condition. These low pH-release type liposomes were prepared by adjusting the ratio of two types of phospholipid derivatives. Loading of geranylgeranyltransferase-I inhibitor (GGTI) generated liposomes with average diameter of 50-100 nm. GGTI release in solution was sharply dependent on pH values, only showing release at pH lower than 6. Release of cargos in a pH dependent manner inside the cell was demonstrated by the use of a proton pump inhibitor Bafilomycin A1 that Increased lysosomal pH and inhibited the release of a dye carried in the pH-liposome. Delivery of GGTI to human pancreatic cancer cells was demonstrated by the inhibition of protein geranylgeranylation inside the cell and this effect was blocked by Bafilomycin A1. In addition, GGTI delivered by pH-liposomes induced proliferation inhibition, G1 cell cycle arrest that is associated with the expression of cell cycle regulator p21CIP1/WAF1. Proliferation inhibition was also observed with various lung cancer cell lines. Availability of nanoformulated GGTI opens up the possibility to combine with other types of inhibitors. To demonstrate this point, we combined the liposomal GGTI with farnesyltransferase inhibitor (FTI) to inhibit K-Ras signaling in pancreatic cancer cells. Our results show that the activated K-Ras signaling in these cells can be effectively inhibited and that synergistic effect of the two drugs is observed. Our results suggest a new direction in the use of GGTI for cancer therapy. PMID- 26352259 TI - Correction: A Collision Probability Model of Portal Vein Tumor Thrombus Formation in Hepatocellular Carcinoma. PMID- 26352260 TI - A Gene Gravity Model for the Evolution of Cancer Genomes: A Study of 3,000 Cancer Genomes across 9 Cancer Types. AB - Cancer development and progression result from somatic evolution by an accumulation of genomic alterations. The effects of those alterations on the fitness of somatic cells lead to evolutionary adaptations such as increased cell proliferation, angiogenesis, and altered anticancer drug responses. However, there are few general mathematical models to quantitatively examine how perturbations of a single gene shape subsequent evolution of the cancer genome. In this study, we proposed the gene gravity model to study the evolution of cancer genomes by incorporating the genome-wide transcription and somatic mutation profiles of ~3,000 tumors across 9 cancer types from The Cancer Genome Atlas into a broad gene network. We found that somatic mutations of a cancer driver gene may drive cancer genome evolution by inducing mutations in other genes. This functional consequence is often generated by the combined effect of genetic and epigenetic (e.g., chromatin regulation) alterations. By quantifying cancer genome evolution using the gene gravity model, we identified six putative cancer genes (AHNAK, COL11A1, DDX3X, FAT4, STAG2, and SYNE1). The tumor genomes harboring the nonsynonymous somatic mutations in these genes had a higher mutation density at the genome level compared to the wild-type groups. Furthermore, we provided statistical evidence that hypermutation of cancer driver genes on inactive X chromosomes is a general feature in female cancer genomes. In summary, this study sheds light on the functional consequences and evolutionary characteristics of somatic mutations during tumorigenesis by propelling adaptive cancer genome evolution, which would provide new perspectives for cancer research and therapeutics. PMID- 26352261 TI - Immune Response of Calves Vaccinated with Brucella abortus S19 or RB51 and Revaccinated with RB51. AB - Brucella abortus S19 and RB51 strains have been successfully used to control bovine brucellosis worldwide; however, currently, most of our understanding of the protective immune response induced by vaccination comes from studies in mice. The aim of this study was to characterize and compare the immune responses induced in cattle prime-immunized with B. abortus S19 or RB51 and revaccinated with RB51. Female calves, aged 4 to 8 months, were vaccinated with either vaccine S19 (0.6-1.2 x 1011 CFU) or RB51 (1.3 x 1010 CFU) on day 0, and revaccinated with RB51 (1.3 x 1010 CFU) on day 365 of the experiment. Characterization of the immune response was performed using serum and peripheral blood mononuclear cells. Blood samples were collected on days 0, 28, 210, 365, 393 and 575 post immunization. Results showed that S19 and RB51 vaccination induced an immune response characterized by proliferation of CD4+ and CD8+ T-cells; IFN-gamma and IL-17A production by CD4+ T-cells; cytotoxic CD8+ T-cells; IL-6 secretion; CD4+ and CD8+ memory cells; antibodies of IgG1 class; and expression of the phenotypes of activation in T-cells. However, the immune response stimulated by S19 compared to RB51 showed higher persistency of IFN-gamma and CD4+ memory cells, induction of CD21+ memory cells and higher secretion of IL-6. After RB51 revaccination, the immune response was chiefly characterized by increase in IFN-gamma expression, proliferation of antigen-specific CD4+ and CD8+ T-cells, cytotoxic CD8+ T-cells and decrease of IL-6 production in both groups. Nevertheless, a different polarization of the immune response, CD4+- or CD8+-dominant, was observed after the booster with RB51 for S19 and RB51 prime-vaccinated animals, respectively. Our results indicate that after prime vaccination both vaccine strains induce a strong and complex Th1 immune response, although after RB51 revaccination the differences between immune profiles induced by prime-vaccination become accentuated. PMID- 26352262 TI - Novel Cross-Border Approaches to Optimise Identification of Asymptomatic and Artemisinin-Resistant Plasmodium Infection in Mobile Populations Crossing Cambodian Borders. AB - BACKGROUND: Human population movement across country borders presents a real challenge for malaria control and elimination efforts in Cambodia and its neighbouring countries. To quantify Plasmodium infection among the border crossing population, including asymptomatic and artemisinin resistant (AR) parasites, three official border crossing points, one from each of Cambodia's borders with Thailand, Laos and Vietnam, were selected for sampling. METHODS AND FINDINGS: A total of 3206 participants (of 4110 approached) were recruited as they crossed the border, tested for malaria and interviewed. By real-time polymerase chain reaction (RT-PCR), 5.4% of all screened individuals were found to harbour Plasmodium parasites. The proportion was highest at the Laos border (11.5%). Overall there were 97 P. vivax (55.7%), 55 P. falciparum (31.6%), two P. malariae (1.1%) and 20 mixed infections (11.5%). Of identified infections, only 20% were febrile at the time of screening. Of the 24 P. falciparum samples where a further PCR was possible to assess AR, 15 (62.5%) had mutations in the K13 propeller domain gene, all from participants at the Laos border point. Malaria rapid diagnostic test (RDT) pLDH/HRP-2 identified a positivity rate of 3.2% overall and sensitivity compared to RT-PCR was very low (43.1%). Main individual risk factors for infection included sex, fever, being a forest-goer, poor knowledge of malaria prevention methods and previous malaria infection. Occupation, day of the week and time of crossing (morning vs. afternoon) also appeared to play an important role in predicting positive cases. CONCLUSIONS: This study offers a novel approach to identify asymptomatic infections and monitor AR parasite flow among mobile and migrant populations crossing the borders. Similar screening activities are recommended to identify other hot borders and characterise potential hot spots of AR. Targeted "customised" interventions and surveillance activities should be implemented in these sites to accelerate elimination efforts in the region. PMID- 26352263 TI - Altered Expression of Wnt Signaling Pathway Components in Osteogenesis of Mesenchymal Stem Cells in Osteoarthritis Patients. AB - INTRODUCTION: Osteoarthritis (OA) is characterized by altered homeostasis of joint cartilage and bone, whose functional properties rely on chondrocytes and osteoblasts, belonging to mesenchymal stem cells (MSCs). WNT signaling acts as a hub integrating and crosstalking with other signaling pathways leading to the regulation of MSC functions. The aim of this study was to evaluate the existence of a differential signaling between Healthy and OA-MSCs during osteogenesis. METHODS: MSCs of seven OA patients and six healthy controls were isolated, characterised and expanded. During in vitro osteogenesis, cells were recovered at days 1, 10 and 21. RNA and protein content was obtained. Expression of WNT pathway genes was evaluated using RT-qPCR. Functional studies were also performed to study the MSC osteogenic commitment and functional and post-traslational status of beta-catenin and several receptor tyrosine kinases. RESULTS: Several genes were downregulated in OA-MSCs during osteogenesis in vitro. These included soluble Wnts, inhibitors, receptors, co-receptors, several kinases and transcription factors. Basal levels of beta-catenin were higher in OA-MSCs, but calcium deposition and expression of osteogenic genes was similar between Healthy and OA-MSCs. Interestingly an increased phosphorylation of p44/42 MAPK (ERK1/2) signaling node was present in OA-MSCs. CONCLUSION: Our results point to the existence in OA-MSCs of alterations in expression of Wnt pathway components during in vitro osteogenesis that are partially compensated by post-translational mechanisms modulating the function of other pathways. We also point the relevance of other signaling pathways in OA pathophysiology suggesting their role in the maintenance of joint homeostasis through modulation of MSC osteogenic potential. PMID- 26352264 TI - Cross-Sectional Associations between Body Size, Circulating Sex-Steroid Hormones and IGF Components among Healthy Chinese Women. AB - The incidence of breast cancer has increased in Asian countries and rates of hormone receptor (HR) negative breast cancer exceed those of Western countries. Epidemiologic data suggest that the association between body size and BC risk may vary by HR status, and could differ geographically. While body size may influence BC risk by moderating the synthesis and metabolism of circulating sex-steroid hormones, insulin-like growth factor (IGF)-1 and related binding proteins, there is a dearth of literature among Asian women. We aimed to examine these specific associations in a sample of Chinese women. In Sichuan Province 143 women aged >=40 years were recruited through outpatient services (2011-2012). Questionnaires, anthropometric measurements, and blood samples were utilized for data collection and linear regression was applied in data analyses. Among women <50 years we observed a non-monotonic positive association between body mass index (BMI) and 17beta-estradiol, and a reversed J-shaped association between BMI and IGF-1 (p <=0.05). We observed similar associations between waist-to-hip ratio and these markers. Our finding of augmented IGF-1 among women with low body mass may have implications for understanding breast tumor heterogeneity in diverse populations and should be evaluated in larger prospective studies with cancer outcomes. PMID- 26352265 TI - Association between Perivascular Spaces and Progression of White Matter Hyperintensities in Lacunar Stroke Patients. AB - OBJECTIVES: Perivascular spaces are associated with MRI markers of cerebral small vessel disease, including white matter hyperintensities. Although perivascular spaces are considered to be an early MRI marker of cerebral small vessel disease, it is unknown whether they are associated with further progression of MRI markers, especially white matter hyperintensities. We determined the association between perivascular spaces and progression of white matter hyperintensities after 2-year follow-up in lacunar stroke patients. METHODS: In 118 lacunar stroke patients we obtained brain MRI and 24-hour ambulatory blood pressure measurements at baseline, and a follow-up brain MRI 2 years later. We visually graded perivascular spaces and white matter hyperintensities at baseline. Progression of white matter hyperintensities was assessed using a visual white matter hyperintensity change scale. Associations with white matter hyperintensity progression were tested with binary logistic regression analysis. RESULTS: Extensive basal ganglia perivascular spaces were associated with progression of white matter hyperintensities (OR 4.29; 95% CI: 1.28-14.32; p<0.05), after adjustment for age, gender, 24-hour blood pressure and vascular risk factors. This association lost significance after additional adjustment for baseline white matter hyperintensities. Centrum semiovale perivascular spaces were not associated with progression of white matter hyperintensities. CONCLUSIONS: Our study shows that extensive basal ganglia perivascular spaces are associated with progression of white matter hyperintensities in cerebral small vessel disease. However, this association was not independent of baseline white matter hyperintensities. Therefore, presence of white matter hyperintensities at baseline remains an important determinant of further progression of white matter hyperintensities in cerebral small vessel disease. PMID- 26352267 TI - Procedural Headache Medicine in Neurology Residency Training: A Survey of US Program Directors. AB - OBJECTIVE: To survey neurology residency program directors (PDs) on trainee exposure, supervision, and credentialing in procedures widely utilized in headache medicine. BACKGROUND: Clinic-based procedures have assumed a prominent role in headache therapy. Headache fellows obtain procedural competence, but reliance on fellowship-trained neurologists cannot match the population eligible for treatments. The inclusion of educational modules and mechanisms for credentialing trainees pursuing procedural competence in residency curricula at individual programs is not known. METHODS: A web-based survey of US neurology residency PDs was designed by the American Headache Society (AHS) procedural special interest section in collaboration with AHS and American Academy of Neurology's Headache and Facial Pain section leadership. The survey addressed exposure, training, and credentialing in: (1) onabotulinumtoxinA (onabotA) injections, (2) extracranial peripheral nerve blocks (PNBs), and (3) trigger point injections (TPIs). RESULTS: Fifty-five PDs (42.6%) completed the survey. Compared to noncompleters, survey completers were more likely to feature headache fellowships at their institutions (38.2% vs 10.8%, P=0.0002). High exposure (onabotA=90.9%, PNBs=80.0%, TPIs=70.9%) usually featured hands-on patient instruction (66.2%) and lectures (55.7%). Supervised performance rates were high (onabotA=65.5%, PNBs=60.0%, TPIs=52.7%), usually in continuity clinic (60.0%) or headache elective (50.9%). Headache specialists (69.1%) or general neurology (32.7%) faculty most commonly trained residents. Formal credentialing was uncommon (16.4-18.2%), mostly by documenting supervised procedures (25.5%). Only 27.3% of programs permitted trainees to perform procedures independently. Most PDs felt procedural exposure (80.0-90.9%) and competence (50.9-56.4%) by all trainees was important. CONCLUSIONS: Resident exposure to procedures for headache is high, but credentialing mechanisms, while desired by most PDs, are not generally in place. Implementation of a credentialing process may ensure trainees enter practice with the ability to perform procedures safely and effectively. PMID- 26352266 TI - Rare Circulating Cells in Familial Waldenstrom Macroglobulinemia Displaying the MYD88 L265P Mutation Are Enriched by Epstein-Barr Virus Immortalization. AB - The MYD88 L265P is a recurrent somatic mutation in neoplastic cells from patients with Waldenstrom Macroglobulinemia (WM). We identified the MYD88 L265P mutation in three individuals from unrelated families, but its presence did not explain the disease segregation within these WM pedigrees. We observed the mutation in these three individuals at high allele fractions in DNA extracted from EBV immortalized Lymphoblastoid cell lines established from peripheral blood (LCL), but at much lower allele fractions in DNA extracted directly from peripheral blood, suggesting that this mutation is present in a clonal cell subpopulation rather than of germ-line origin. Furthermore, we observed that the MYD88 L265P mutation is enriched in WM families, detected in 40.5% of patients with familial WM or MGUS (10/22 WM, 5/15 MGUS), compared to 3.5% of patients with familial MM or MGUS (0/72 MM, 4/41 MGUS) (p = 10-7). The mutant allele frequency increased with passages in vitro after immortalization with Epstein-Barr virus (EBV) consistent with the MYD88 L265P described gain-of-function proposed for this mutation. The MYD88 L265P mutation appears to be frequently present in circulating cells in patients with WM, and MGUS, and these cells are amenable to immortalization by EBV. PMID- 26352268 TI - Nebulisation of IVT mRNA Complexes for Intrapulmonary Administration. AB - During the last years the potential role of in vitro transcribed (IVT) mRNA as a vehicle to deliver genetic information has come into focus. IVT mRNA could be used for anti-cancer therapies, vaccination purposes, generation of pluripotent stem cells and also for genome engineering or protein replacement. However, the administration of IVT mRNA into the target organ is still challenging. The lung with its large surface area is not only of interest for delivery of genetic information for treatment of e.g. for cystic fibrosis or alpha-1-antitrypsin deficiency, but also for vaccination purposes. Administration of IVT mRNA to the lung can be performed by direct intratracheal instillation or by aerosol inhalation/nebulisation. The latter approach shows a non-invasive tool, although it is not known, if IVT mRNA is resistant during the process of nebulisation. Therefore, we investigated the transfection efficiency of non-nebulised and nebulised IVT mRNA polyplexes and lipoplexes in human bronchial epithelial cells (16HBE). A slight reduction in transfection efficiency was observed for lipoplexes (Lipofectamine 2000) in the nebulised part compared to the non nebulised which can be overcome by increasing the amount of Lipofectamine. However, Lipofectamine was more than three times more efficient in transfecting 16HBE than DMRIE and linear PEI performed almost 10 times better than its branched derivative. By contrast, the nebulisation process did not affect the cationic polymer complexes. Furthermore, aerosolisation of IVT mRNA complexes did neither affect the protein duration nor the toxicity of the cationic complexes. Taken together, these data show that aerosolisation of cationic IVT mRNA complexes constitute a potentially powerful means to transfect cells in the lung with the purpose of protein replacement for genetic diseases such as cystic fibrosis or alpha-1-antitrypsin deficiency or for infectious disease vaccines, while bringing along the advantages of IVT mRNA as compared to pDNA as transfection agent. PMID- 26352269 TI - Mechanism of Action and Initial, In Vitro SAR of an Inhibitor of the Shigella flexneri Virulence Regulator VirF. AB - Shigella spp. are among the main causative agents of acute diarrheal illness and claim more than 1 million lives per year worldwide. There are multiple bacterial genes that control the pathogenesis of Shigella, but the virF gene may be the most important. This gene, located on the primary pathogenicity island of Shigella, encodes VirF, an AraC-family transcriptional activator that is responsible for initiating the pathogenesis cycle in Shigella. We have previously shown that it is possible to attenuate the virulence of Shigella flexneri via small molecule inhibition of VirF. In this study, we probed the mechanism of action of our small molecule inhibitors of VirF. To enable these studies, we have developed a homologous and efficient expression and purification system for VirF and have optimized two different in vitro VirF-DNA binding assays. We have determined that one of our HTS hit compounds inhibits VirF binding to DNA with a calculated Ki similar to the effective doses seen in our transcriptional activation and virulence screens. This is consistent with inhibition of DNA binding as the mechanism of action of this hit compound. We have also screened 15 commercially sourced analogs of this compound and deduced an initial SAR from the approximately 100-fold range in activities. Our four other HTS hit compounds do not inhibit DNA binding and yet they do block VirF activity. This suggests that multiple agents with different molecular mechanisms of inhibition of VirF could be developed. Pursuing hits with different mechanisms of action could be a powerful approach to enhance activity and to circumvent resistance that could develop to any one of these agents. PMID- 26352271 TI - Bidirectional Echolocation in the Bat Barbastella barbastellus: Different Signals of Low Source Level Are Emitted Upward through the Nose and Downward through the Mouth. AB - The Barbastelle bat (Barbastella barbastellus) preys almost exclusively on tympanate moths. While foraging, this species alternates between two different signal types. We investigated whether these signals differ in emission direction or source level (SL) as assumed from earlier single microphone recordings. We used two different settings of a 16-microphone array to determine SL and sonar beam direction at various locations in the field. Both types of search signals had low SLs (81 and 82 dB SPL rms re 1 m) as compared to other aerial-hawking bats. These two signal types were emitted in different directions; type 1 signals were directed downward and type 2 signals upward. The angle between beam directions was approximately 70 degrees . Barbastelle bats are able to emit signals through both the mouth and the nostrils. As mouth and nostrils are roughly perpendicular to each other, we conclude that type 1 signals are emitted through the mouth while type 2 signals and approach signals are emitted through the nose. We hypothesize that the "stealth" echolocation system of B. barbastellus is bifunctional. The more upward directed nose signals may be mainly used for search and localization of prey. Their low SL prevents an early detection by eared moths but comes at the expense of a strongly reduced detection range for the environment below the bat. The more downward directed mouth signals may have evolved to compensate for this disadvantage and may be mainly used for spatial orientation. We suggest that the possibly bifunctional echolocation system of B. barbastellus has been adapted to the selective foraging of eared moths and is an excellent example of a sophisticated sensory arms race between predator and prey. PMID- 26352270 TI - Whole-Exome Sequencing in a South American Cohort Links ALDH1A3, FOXN1 and Retinoic Acid Regulation Pathways to Autism Spectrum Disorders. AB - Autism spectrum disorders (ASDs) are a range of complex neurodevelopmental conditions principally characterized by dysfunctions linked to mental development. Previous studies have shown that there are more than 1000 genes likely involved in ASD, expressed mainly in brain and highly interconnected among them. We applied whole exome sequencing in Colombian-South American trios. Two missense novel SNVs were found in the same child: ALDH1A3 (RefSeq NM_000693: c.1514T>C (p.I505T)) and FOXN1 (RefSeq NM_003593: c.146C>T (p.S49L)). Gene expression studies reveal that Aldh1a3 and Foxn1 are expressed in ~E13.5 mouse embryonic brain, as well as in adult piriform cortex (PC; ~P30). Conserved Retinoic Acid Response Elements (RAREs) upstream of human ALDH1A3 and FOXN1 and in mouse Aldh1a3 and Foxn1 genes were revealed using bioinformatic approximation. Chromatin immunoprecipitation (ChIP) assay using Retinoid Acid Receptor B (Rarb) as the immunoprecipitation target suggests RA regulation of Aldh1a3 and Foxn1 in mice. Our results frame a possible link of RA regulation in brain to ASD etiology, and a feasible non-additive effect of two apparently unrelated variants in ALDH1A3 and FOXN1 recognizing that every result given by next generation sequencing should be cautiously analyzed, as it might be an incidental finding. PMID- 26352272 TI - [Shock wave lithotripsy, retrograde intrarenal surgery or percutaneous nephrolithotomy for lower pole renal stones?]. AB - Among the therapeutic alternatives available for the treatment of lower pole renal calculi are extracorporeal lithotripsy, percutaneous nephrolithotomy and retrograde intrarenal surgery. There is controversy about which of these techniques is more effective, especially for stones smaller than 20 mm. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified four systematic reviews including 11 pertinent randomized controlled trials overall. We combined the evidence and generated a summary of findings following the GRADE approach. We concluded percutaneous nephrolithotomy probably increases success rate, but it is not clear if it decreases the need of retreatment compared to extracorporeal shock wave lithotripsy. In comparison to retrograde intrarenal surgery, it may increase success rate, but it is not clear if it decreases the need of retreatment. Retrograde intrarenal surgery may increase success rate, and probably decreases need of retreatment compared to extracorporeal shock wave lithotripsy. PMID- 26352273 TI - Sulfur vacancy activated field effect transistors based on ReS2 nanosheets. AB - Rhenium disulphide (ReS2) is a recently discovered new member of the transition metal dichalcogenides. Most impressively, it exhibits a direct bandgap from bulk to monolayer. However, the growth of ReS2 nanosheets (NSs) still remains a challenge and in turn their applications are unexplored. In this study, we successfully synthesized high-quality ReS2 NSs via chemical vapor deposition. A high-performance field effect transistor of ReS2 NSs with an on/off ratio of ~10(5) was demonstrated. Through both electrical transport measurements at varying temperatures (80 K-360 K) and first-principles calculations, we find sulfur vacancies, which exist intrinsically in ReS2 NSs and significantly affect the performance of the ReS2 FET device. Furthermore, we demonstrated that sulfur vacancies can efficiently adsorb and recognize oxidizing (O2) and reducing (NH3) gases, which electronically interact with ReS2 only at defect sites. Our findings provide experimental groundwork for the synthesis of new transition metal dichalocogenides, supply guidelines for understanding the physical nature of ReS2 FETs, and offer a new route toward tailoring their electrical properties by defect engineering in the future. PMID- 26352274 TI - Distribution and evolution of the serine/aspartate racemase family in invertebrates. AB - Free D-amino acids have been found in various invertebrate phyla, while amino acid racemase genes have been identified in few species. The purpose of this study is to elucidate the distribution, function, and evolution of amino acid racemases in invertebrate animals. We searched the GenBank databases, and found 11 homologous serine racemase genes from eight species in eight different invertebrate phyla. The cloned genes were identified based on their maximum activity as Acropora millepora (Cnidaria) serine racemase (SerR) and aspartate racemase (AspR), Caenorhabditis elegans (Nematoda) SerR, Capitella teleta (Annelida) SerR, Crassostrea gigas (Mollusca) SerR and AspR, Dugesia japonica (Platyhelminthes) SerR, Milnesium tardigradum (Tardigrada) SerR, Penaeus monodon (Arthropoda) SerR and AspR and Strongylocentrotus purpuratus (Echinodermata) AspR. We found that Acropora, Aplysia, Capitella, Crassostrea and Penaeus had two amino acid racemase paralogous genes and these paralogous genes have evolved independently by gene duplication at their recent ancestral species. The transcriptome analyses using available SRA data and enzyme kinetic data suggested that these paralogous genes are expressed in different tissues and have different functions in vivo. Phylogenetic analyses clearly indicated that animal SerR and AspR are not separated by their particular racemase functions and form a serine/aspartate racemase family cluster. Our results revealed that SerR and AspR are more widely distributed among invertebrates than previously known. Moreover, we propose that the triple serine loop motif at amino acid positions 150-152 may be responsible for the large aspartate racemase activity and the AspR evolution from SerR. PMID- 26352276 TI - Pitavastatin attenuates monocyte activation in response to orthopedic implant derived wear particles by suppressing the NF-kappaB signaling pathway. AB - Aseptic loosening secondary to particle-induced periprosthetic osteolysis is considered to be the primary cause of long-term implant failure in orthopedic surgery. Implant-derived wear particles activate and recruit macrophages and osteoclasts, which cause a persistent inflammatory response with bone destruction that is followed by a loosening of the implant. Thus, strategies for inhibiting macrophage and osteoclast function may provide a therapeutic benefit for preventing aseptic loosening. The aim of the present study was to determine the effects of pitavastatin on the activation and cytokine response of polymethyl methacrylate (PMMA) particle-induced monocytes. Peripheral blood monocytes were obtained and treated with PMMA and pitavastatin. ELISA demonstrated that pitavastatin inhibited mRNA and protein expression of interleukin (IL)-1beta, IL 6 and tumor necrosis factor-alpha. Western blot analysis and immunofluorescence staining demonstrated that pitavastatin downregulated inhibitor of kappaB phosphorylation and degradation, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) p65 translocation. Together, these results indicate that pitavastatin may attenuate monocyte activation in response to orthopedic implant wear particles by suppression of the NF-kappaB signaling pathway. PMID- 26352275 TI - CD163 and CD206 expression does not correlate with tolerance and cytokine production in LPS-tolerant human monocytes. AB - BACKGROUND: Lipopolysaccharide (LPS)-tolerant monocytes produce small amounts of inflammatory cytokines, which is one of the characteristics of the alternative activated macrophages (AAM). These cells exhibited an increased expression of CD206 and CD163. Given the functional similarities of AAMs with the modulation of monocytes' functions observed during sepsis and LPS-tolerance, we evaluated whether the inhibition of inflammatory cytokine production by LPS-tolerant monocytes is associated with the phenotype of cells expressing CD206 and CD163. METHODS: We investigated whether tolerant human monocytes would modulate their expression of CD206 and CD163, markers of alternative activation, and whether the level of their expression would be related to cytokines detection. Tolerance to LPS was induced in peripheral blood mononuclear cell by pre-incubating the cells with increasing concentrations of LPS. The expression of CD206 and CD163 and intracellular TNF-alpha and IL-6 was determined 24 h after LPS challenge by flow cytometry. RESULTS: No differences in CD163 expression were observed between tolerant and non-tolerant cells, while the expression of CD206, which was decreased following LPS stimulation in non-tolerized cells, was further reduced in tolerant cells. Decreased production of inflammatory cytokines was observed in the tolerized cells, regardless of the expression of CD163 and CD206, with the exception of IL-6 in CD206+ monocytes, which was similarly expressed in both tolerized and non-tolerized cells. CONCLUSIONS: The effect of LPS in the expression of CD163 and CD206 on monocytes is not reverted in LPS tolerant cells, and the inhibition of inflammatory cytokines in tolerant cells is not related with modulation of these receptors. (c) 2016 International Clinical Cytometry Society. PMID- 26352277 TI - Effect of ascorbic acid (vitamin C) on the ESR spectra of the red and black hair: pheomelanin free radicals are not always present in red hair. AB - Increased incidence of melanoma in the population with red hair is conditioned by synthesis of pheomelanin pigments in the skin and their phototoxic properties. The recent research has shown that free radicals of pheomelanin are produced not only by the influence of UV irradiation, but also in UV-independent pathways of oxidative stress. It has been ascertained, that the color of the hair is not always determinant of the amount of pheolemanin radicals in red hair. Therefore, in order to evaluate the risk of melanoma in different individuals, it is necessary to define the amount of free radicals of pheomelanin in red hair using ESR spectroscopy method. Besides, it is very important to find effective antioxidant, capable of neutralizing free radicals of pheomelanin. It was proved that ascorbic acid neutralizes free radicals of pheomelanin very effectively. The main goal of our research was to define the presumably optimal concentration of ascorbic acid as an antioxidant and study the kinetics of the influence of this concentration on red and black hair. It has been found out, that ascorbic acid influences the free radicals of red and black hair, and its appropriate optimal concentration is 10 mM. The obtained results can be considered in dermatology and cosmetology. PMID- 26352278 TI - Determination of the Hypnotic Potency in Rats of the Novel Ketamine Ester Analogue SN 35210. AB - BACKGROUND: Ketamine is a rapidly acting dissociative anaesthetic drug with additional sympathomimetic, analgesic, and antidepressant properties. Despite these advantages, clinical use is curtailed by prolonged psychomimetic effects apparent over the entire dose spectrum. In this study, we report on the hypnotic potency of SN 35210, the first ketamine ester-analogue designed for rapid offset via esterase-mediated hydrolysis. METHODS: Thirty-three adult Sprague Dawley rats received intravenous racemic ketamine (n = 14), racemic SN 35210 (n = 19), S enantiomer SN 35210 (n = 17), or R-enantiomer SN 35210 (n = 15), in crossover design. The ability to induce loss of righting reflex (LORR) at a given dose, the duration of righting reflex loss, and the time to return of normal behaviours were recorded. The ED50 for LORR was determined for all agents. RESULTS: The ED50 for righting reflex loss was racemic ketamine 9.6 (95% CI 8.5-10.9) mg/kg, racemic SN 35210 10.4 (95% CI 9.5-11.5) mg/kg, S-enantiomer SN 35210 10.6 (95% CI 9.1-11.8), and R-enantiomer SN 35210 10.3 (95% CI 9.1-11.4) mg/kg. The duration of righting reflex loss and time to return to normal behaviours were approximately 5 times greater for racemic ketamine than all 3 SN 35210 ester analogues. CONCLUSIONS: Racemic, and R and S-enantiomer SN 35210, produced LORR in rats at similar doses to the parent compound ketamine. The duration of righting reflex loss, and duration of behavioural aberration, was significantly reduced for all SN 35210 analogues. PMID- 26352279 TI - Inhibition of cell proliferation and metastasis of human hepatocellular carcinoma by miR-137 is regulated by CDC42. AB - In the present study, we evaluated the mechanisms of CDC42 in association with the microRNA-137 (miR-137)-induced inhibition of human hepatocellular carcinoma (HCC). The gene expression levels of miR-137 were evaluated in HCC cell lines. Direct association of miR-137 with its downstream target, cell division control protein 42 (CDC42), was evaluated by dual-luciferase assay, western blot analysis and correlation analysis using clinical tumor samples. In the HCC HuH7 and MHCC97L cell lines, miR-137 was upregulated to inhibit cell proliferation and metastasis in vitro and tumor growth in vivo. CDC42 was overexpressed in the HuH7 and MHCC97L cells to evaluate its effect on the miR-137-mediated antitumor effects. Furthermore, possible crosstalk between CDC42 and another miR-137 target gene, AKT2, was evaluated by co-overexpressing CDC42 and AKT2 in the HuH7 and MHCC97L cells and examining their effects on miR-137-mediated HCC regulation. miR 137 was confirmed to be downregulated in the HCC cell lines. Dual-luciferase assay showed that CDC42 was directly targeted by miR-137, and western blotting showed that CDC42 was downregulated by miR-137 upregulation in the HuH7 and MHCC97L cells. In human tumors, the expression levels of CDC42 and miR-137 were inversely correlated. The inhibitory effects of miR-137 on HCC proliferation, metastasis and in vivo tumor growth were all ameliorated by CDC42 overexpression. Furthermore, co-overexpression of AKT2 in addition to CDC42 additively reduced the inhibition of miR-137 on HCC proliferation and metastasis, suggesting two independent pathways of CDC42 and AKT2 in miR-137-mediated HCC regulation. Our study demonstrated that CDC42 independently regulated the antitumor effects of miR-137 in human HCC. PMID- 26352280 TI - Adverse outcome after incident stroke hospitalization for Indigenous and non Indigenous Australians in the Northern Territory. AB - BACKGROUND: Survival after a stroke is lower for Indigenous than other stroke patients in Australia. It is not known whether recurrence is more common for Indigenous patients, or whether their higher prevalence of comorbidity affects their lower survival. AIMS: This study aimed to investigate the stroke recurrence and role of comorbidities in adverse stroke outcomes (recurrence and death) for Indigenous compared with other Australians. METHODS: A retrospective cohort study of first hospitalization for stroke (n = 2105) recorded in Northern Territory hospital inpatient data between 1996 and 2011 was conducted. For the multivariable analyses of adverse outcomes, logistic regression was used for case fatality and competing risk analysis for recurrent stroke and long-term death. Comorbidities (identified from inpatient diagnosis data) were analyzed using the Charlson Comorbidity Index (modified for stroke outcomes). RESULTS: Prevalence of comorbidities, case fatality, incidence of re-hospitalization for recurrent stroke, and long-term death rate were higher for Indigenous than non-Indigenous stroke patients. Adjustment for comorbidity in multivariable analyses considerably reduced Indigenous patients' excess risk for case fatality (odds ratio: 1.25, 0.88-1.78) and long-term death (standard hazard ratio: 1.27, 1.01 1.61) (but not recurrence), implying that their excess risk of death was in part due to higher comorbidity prevalence. CONCLUSION: Indigenous stroke patients have higher prevalence of comorbidities than non-Indigenous stroke patients, which explained part of the disparity in both case fatality and long-term survival but did not explain the disparity in stroke recurrence at all. PMID- 26352281 TI - Bone morphogenetic protein 2 regulates the differentiation of nitrergic enteric neurons by modulating Smad1 signaling in slow transit constipation. AB - Bone morphogenetic proteins (BMPs) belong to the transforming growth factor superfamily and have been implicated in chondrogenesis and neuronal differentiation. In order to examine the function of bone morphogenetic protein 2 (BMP-2) on the differentiation of nitrergic enteric neurons in slow transit constipation (STC), the expression of BMP-2 and neuronal nitric oxide synthase (nNOS) was investigated in the myenteric nerve plexus in STC and control tissues by immunohistochemical assays. The present study demonstrated that BMP-2 and nNOS were expressed in the myenteric nerve plexus and their levels were differentially altered in the STC group and control group. In addition, the effect of BMP-2 on primary myenteric neurons was investigated by measuring the neurite length. The results demonstrated that BMP-2 regulated the differentiation of primary enteric neurons and increased the length of neurites compared with the control group. In addition, the effect of BMP-2 on the expression of nNOS was also investigated in primary enteric neurons and the Smad1 signal transduction pathway by western blot analysis, reverse transcription quantitative polymerase chain reaction and immunofluorescence assay. The results suggested that BMP-2 promoted the expression of nNOS in primary myenteric neurons and induced phosphorylation of Smad1. These data indicate a new role for BMP-2 as an important transcriptional cofactor that regulates the differentiation of nitrergic enteric neurons through the Smad1 pathway. Intervention of BMP-2 may be useful for the treatment of STC. PMID- 26352283 TI - A rewarding mission. PMID- 26352282 TI - Simulated pressure changes in multilayer, multicomponent wrap systems when transitioning from rest to standing. AB - OBJECTIVE: The objective of this paper was to investigate the pressure applied to the lower leg by multilayer, multicomponent wrap systems, in different positions Method: The stretch profiles of five multilayer, multicomponent wrap systems were tested, three 2-layer and two 4-layer systems. These were quantified in the laboratory using a tensile testing device. The circumference of the lower leg was measured on healthy participants in three locations (ankle, B1 level, and calf) in three different postures (rest, dorsiflexion, and standing). RESULTS: The largest changes in circumference were used to simulate the pressure changes under the multilayer, multicomponent products using Laplace's Law. While the pressure differences were large for the zinc plaster product, pressure changes ranged from 5-10mmHg for the other, more elastic products. Additionally, it was noted that the leg decreased in circumference at the B1 level and calf for the majority of participants when transitioning from sitting to standing. This decrease in size results in a decrease in bandage tension and applied pressure. CONCLUSION: These results show that the sub-bandage pressure is not significantly affected by changes in posture when used as intended, within the therapeutic range. DECLARATION OF INTEREST: This study was sponsored by Carolon. L. Reid, and S. Kravitz are employees of Carolon and E. Grant is a Member of the Board. M. Hegarty-Craver and C. Kwon have received monetary compensation as researchers for Carolon. PMID- 26352284 TI - Use of NPWT with and without Soft Port technology in infected foot wounds undergoing partial diabetic foot amputation. AB - OBJECTIVE: Negative pressure wound therapy (NPWT) has previously been shown to be effective in closing diabetic foot wounds that have undergone amputation over a 16-week period. For patients with plantar foot wounds, NPWT is a key therapy. An alternative NPWT with and without a novel soft, flexible port system needs to be evaluated for its comparable efficacy. Our objective was to show the non inferiority of an alternative negative pressure system, and in a small subset, a novel foam dressing system. METHOD: We performed a single centre prospective study of patients with diabetes undergoing open bone resection in the foot for acutely infected wounds. Wounds were treated with NPWT/soft port technology (SPT), for 112 days or until primary closure or the wound was deemed ready for delayed primary closure. Rate of closure and quality of life were analysed. A previously published cohort was used as a control. RESULTS: Of the 30 patients initially recruited, 29 met eligibility requirements and had NPWT applied a median of 2 days postoperatively. There were seven patients (24%) who had delayed primary closure (mean=58 days) and 52% had sufficient progress to change in treatment (15/29; mean=62 days). Only one patient reached the 112-day mark without sufficient progress to be closed. The primary method of delayed primary closure was split-thickness skin graft. There was a reduction in wound area 56.3% (initial mean area=17.4cm(2) to final mean area=7.6 cm(2); p=0.001) at the end of treatment (mean=58.7 days) reduced to 4.3cm(2) a 67.2% reduction (p=0.004) at the end of study (112 days). CONCLUSION: The alternative NPWT and the soft port technology was well tolerated and effective in the population in aggregate. There was no inferiority between the two technologies. The aggregate closure or progression to be ready for closure rate of 75% at 69 days compares very favourably with previously published data for NPWT in this population of 56% at 56 days (range: 26-92 days). Both cohorts did significantly better than previously published standard of care closure rates of 39% at 77 days. DECLARATION OF INTEREST: J.C. Lantis is a paid consultant for Smith & Nephew, Acelity, Macrocure and Manukamed. This trial as supported by an institutional grant to St Luke's and Roosevelt Hospital sponsored by Smith & Nephew. The outcome of the trial had no bearing on the condition of the grant. No investigator holds an equity position in Smith & Nephew. C. Gendics is a paid consultant of Acelity. PMID- 26352285 TI - Electron confinement induced by diluted hydrogen-like ad-atoms in graphene ribbons. AB - We report the electronic properties of two-dimensional systems made of graphene nanoribbons, which are patterned with ad-atoms in two separated regions. Due to the extra electronic confinement induced by the presence of impurities, we find resonant levels, quasi-bound and impurity-induced localized states, which determine the transport properties of the system. Regardless of the ad-atom distribution in the system, we apply band-folding procedures to simple models and predict the energies and the spatial distribution of those impurity-induced states. We take into account two different scenarios: gapped graphene and the presence of randomly distributed ad-atoms in a low dilution regime. In both cases the defect-induced resonances are still detected. Our findings would encourage experimentalists to synthesize these systems and characterize their quasi localized states by employing, for instance, scanning tunneling spectroscopy (STS). Additionally, the resonant transport features could be used in electronic applications and molecular sensing devices. PMID- 26352287 TI - Postfunctionalization of polyoxometalates: an efficient strategy to construct organic-inorganic zwitterions. AB - A class of monoorganoimido-substituted hexamolybdates containing a pyridine group have been firstly synthesized. Furthermore, a reaction protocol of alkylation based on the resulting pyridine-functionalized hexamolybdates has been developed, with which a type of zwitterionic clusters has been successfully obtained. PMID- 26352286 TI - Systems biology and mechanics of growth. AB - In contrast to inert systems, living biological systems have the advantage to adapt to their environment through growth and evolution. This transfiguration is evident during embryonic development, when the predisposed need to grow allows form to follow function. Alterations in the equilibrium state of biological systems breed disease and mutation in response to environmental triggers. The need to characterize the growth of biological systems to better understand these phenomena has motivated the continuum theory of growth and stimulated the development of computational tools in systems biology. Biological growth in development and disease is increasingly studied using the framework of morphoelasticity. Here, we demonstrate the potential for morphoelastic simulations through examples of volume, area, and length growth, inspired by tumor expansion, chronic bronchitis, brain development, intestine formation, plant shape, and myopia. We review the systems biology of living systems in light of biochemical and optical stimuli and classify different types of growth to facilitate the design of growth models for various biological systems within this generic framework. Exploring the systems biology of growth introduces a new venue to control and manipulate embryonic development, disease progression, and clinical intervention. PMID- 26352288 TI - The Association Between Parkinson's Disease Motor Impairments and Pain. AB - OBJECTIVE: This study aimed to: 1) examine the severity and frequency of pain and the extent to which pain interferes with work and 2) explore the contributions of motor impairments to pain in people with Parkinson's disease (PD). METHOD: Pain severity, frequency and the impact of pain on work were determined using subscores from the SF-36TM, Parkinson's Disease Questionnaire and SF-12v2TM, respectively, in 231 people with Parkinson's disease. Motor impairments were measured using the Unified Parkinson's Disease Rating Scale. Freezing of gait was determined as its presence or absence in the last month. Associations between impairments and pain were examined using logistic regression. RESULTS: Pain was reported by 187 (81%) participants, with 91 (39%) reporting pain of moderate severity or worse. Pain interfered with work to some extent in 158 (68%) participants. After adjusting for age and gender, increased rigidity was associated with higher pain frequency and more pain that interfered with work (for both models, Odds Ratio = 1.14, 95% confidence interval 1.0-1.3). Tremor was not associated with any measures of pain and motor impairments were not associated with pain severity. CONCLUSIONS: Most people with PD experience pain at least monthly and pain interferes with daily activities. PD impairments are associated with more frequent pain and pain that interferes with work, with rigidity having the strongest association. Development of Parkinson's disease specific pain assessments and further investigation into the association between PD impairments and pain is warranted. PMID- 26352289 TI - Modification of postmortem wounds by Dermestes maculatus (Coleoptera: Dermestidae) activity: A preliminary study. AB - The purpose of this analysis was to evaluate the effects of insect activity on hacking trauma which was inflicted with a small cleaver and a razor blade under controlled conditions. Three pig hooves were each subjected to a blow with a small cleaver and a cut with a razor blade prior to insect exposure. We used Dermestes maculatus DeGeer 1774 species. These beetles made principally depressions and destruction on both wounds, and bites were observed on the edges of the wounds. As time passed and insects fed and refuge, chop marks were deformed and disappeared, taking this less than a month. Thus, D. maculatus could mask postmortem wounds and probably premortem wounds, and so the cause of death. PMID- 26352290 TI - Ultrastructure variation in the spermatozoa of Pseudopaludicola frogs (Amphibia, Anura, Leptodactylidae), with brief comments on its phylogenetic relevance. AB - The taxonomic history of the small frogs of the genus Pseudopaludicola from South America has been controversial. Phylogenetic inferences based on molecular data have identified four Pseudopaludicola clades, correlating with the known variation in karyotypes (2n = 22, 20, 18, and 16). In this study, the ultrastructure of the spermatozoa was analyzed in 12 species of the Pseudopaludicola, with the aim of describing their morphology and identifying characters that may contribute to a better understanding of the phylogenetic relationships. The spermatozoa presented marked differences in tail structures. The tails of the spermatozoa of the species with 2n = 22 chromosomes (Pseudopaludicola sp. 1 [P. pusilla group], Pseudopaludicola falcipes, P. mineira, and Pseudopaludicola saltica), as well as Pseudopaludicola ameghini and Pseudopaludicola ternetzi (2n=20), have juxta-axonemal fibers, undulating membranes and axial fibers. In contrast, in the species with 2n = 18 (P. facureae, P. giarettai, Pseudopaludicola canga, P. atragula, and Pseudopaludicola sp. 2) and 2n = 16 (Pseudopaludicola mystacalis), there are no evident axial or juxta-axonemal fibers, but a paraxonemal rod with a thick undulating membrane, which is shorter than that found among Pseudopaludicola species. The ultrastructural morphological differences observed in the spermatozoa of these species may be phylogenetically informative, given that they coincide with the consensus phylogeny of the group and appear to represent a progressive simplification of the spermatozoon. PMID- 26352291 TI - Automatic liver contouring for radiotherapy treatment planning. AB - To develop automatic and efficient liver contouring software for planning 3D-CT and four-dimensional computed tomography (4D-CT) for application in clinical radiation therapy treatment planning systems.The algorithm comprises three steps for overcoming the challenge of similar intensities between the liver region and its surrounding tissues. First, the total variation model with the L1 norm (TV L1), which has the characteristic of multi-scale decomposition and an edge preserving property, is used for removing the surrounding muscles and tissues. Second, an improved level set model that contains both global and local energy functions is utilized to extract liver contour information sequentially. In the global energy function, the local correlation coefficient (LCC) is constructed based on the gray level co-occurrence matrix both of the initial liver region and the background region. The LCC can calculate the correlation of a pixel with the foreground and background regions, respectively. The LCC is combined with intensity distribution models to classify pixels during the evolutionary process of the level set based method. The obtained liver contour is used as the candidate liver region for the following step. In the third step, voxel-based texture characterization is employed for refining the liver region and obtaining the final liver contours.The proposed method was validated based on the planning CT images of a group of 25 patients undergoing radiation therapy treatment planning. These included ten lung cancer patients with normal appearing livers and ten patients with hepatocellular carcinoma or liver metastases. The method was also tested on abdominal 4D-CT images of a group of five patients with hepatocellular carcinoma or liver metastases. The false positive volume percentage, the false negative volume percentage, and the dice similarity coefficient between liver contours obtained by a developed algorithm and a current standard delineated by the expert group are on an average 2.15-2.57%, 2.96-3.23%, and 91.01-97.21% for the CT images with normal appearing livers, 2.28 3.62%, 3.15-4.33%, and 86.14-93.53% for the CT images with hepatocellular carcinoma or liver metastases, and 2.37-3.96%, 3.25-4.57%, and 82.23-89.44% for the 4D-CT images also with hepatocellular carcinoma or liver metastases, respectively.The proposed three-step method can achieve efficient automatic liver contouring for planning CT and 4D-CT images with follow-up treatment planning and should find widespread applications in future treatment planning systems. PMID- 26352292 TI - Peptides from the scorpion Vaejovis punctatus with broad antimicrobial activity. AB - The antimicrobial potential of two new non-disulfide bound peptides, named VpAmp1.0 (LPFFLLSLIPSAISAIKKI, amidated) and VpAmp2.0 (FWGFLGKLAMKAVPSLIGGNKSSSK) is here reported. These are 19- and 25-aminoacid-long peptides with +2 and +4 net charges, respectively. Their sequences correspond to the predicted mature regions from longer precursors, putatively encoded by cDNAs derived from the venom glands of the Mexican scorpion Vaejovis punctatus. Both peptides were chemically synthesized and assayed against a variety of microorganisms, including pathogenic strains from clinical isolates and strains resistant to conventional antibiotics. Two shorter variants, named VpAmp1.1 (FFLLSLIPSAISAIKKI, amidated) and VpAmp2.1 (FWGFLGKLAMKAVPSLIGGNKK), were also synthesized and tested. The antimicrobial assays revealed that the four synthetic peptides effectively inhibit the growth of both Gram-positive (Staphylococcus aureus and Streptococcus agalactiaea) and Gram-negative (Escherichia coli and Pseudomonas aeruginosa) bacteria, with MICs in the range of 2.5-24.0 MUM; yeasts (Candida albicans and Candida glabrata) with MICs of 3.1-50.0 MUM; and two clinically isolated strains of Mycobacterium tuberculosis-including a multi-drug resistant one- with MICs in the range of 4.8 30.5 MUM. A comparison between the activities of the original peptides and their derivatives gives insight into the structural/functional role of their distinctive residues. PMID- 26352293 TI - Use of Synergistic Interactions to Fabricate Strong, Tough, and Conductive Artificial Nacre Based on Graphene Oxide and Chitosan. AB - Graphene is the strongest and stiffest material, leading to the development of promising applications in many fields. However, the assembly of graphene nanosheets into macrosized nanocomposites for practical applications remains a challenge. Nacre in its natural form sets the "gold standard" for toughness and strength, which serves as a guide to the assembly of graphene nanosheets into high-performance nanocomposites. Here we show the strong, tough, conductive artificial nacre based on graphene oxide through synergistic interactions of hydrogen and covalent bonding. Tensile strength and toughness was 4 and 10 times higher, respectively, than that of natural nacre. The exceptional integrated strong and tough artificial nacre has promising applications in aerospace, artificial muscle, and tissue engineering, especially for flexible supercapacitor electrodes due to its high electrical conductivity. The use of synergistic interactions is a strategy for the development of high-performance nanocomposites. PMID- 26352294 TI - Impact of Bowel Preparation with Low-Volume (2-Liter) and Intermediate-Volume (3 Liter) Polyethylene Glycol on Colonoscopy Quality: A Prospective Observational Study. AB - BACKGROUND/AIMS: Two-liter polyethylene glycol (PEG) is the most commonly used bowel-cleansing regimen in Taiwan, but its efficacy is unsatisfactory. The aim of this study was to compare 2-liter and 3-liter PEG in terms of their impact on colonoscopy quality among an average-risk population. METHODS: Two-liter PEG was provided between August 2012 and May 2013, while 3-liter PEG was provided between June 2013 and March 2014. A split-dose regimen was provided for morning colonoscopy and a same-day regimen was provided for afternoon colonoscopy. The level of bowel cleansing was prospectively scored. RESULTS: A total of 407 consecutive subjects completed the 2-liter regimen, and another 407 consecutive subjects completed the 3-liter regimen. The 3-liter group had a significantly higher rate of excellent or good preparations, equivalent to a Boston bowel preparation scale of >=7, than the 2-liter group (90 vs. 73%, p < 0.0001). More subjects in the 3-liter preparation group compared with the 2-liter group had overall adenoma (70 vs. 54%, p < 0.0001), proximal adenoma (47 vs. 35%, p = 0.0006), sessile serrated adenoma (28 vs. 6%, p < 0.0001), and advanced adenoma (21 vs. 9%, p < 0.0001). CONCLUSIONS: Three-liter PEG provided better cleansing quality and higher adenoma detection rate than 2-liter PEG. PMID- 26352295 TI - Li Intercalation in MoS2: In Situ Observation of Its Dynamics and Tuning Optical and Electrical Properties. AB - Two-dimensional layered materials like MoS2 have shown promise for nanoelectronics and energy storage, both as monolayers and as bulk van der Waals crystals with tunable properties. Here we present a platform to tune the physical and chemical properties of nanoscale MoS2 by electrochemically inserting a foreign species (Li(+) ions) into their interlayer spacing. We discover substantial enhancement of light transmission (up to 90% in 4 nm thick lithiated MoS2) and electrical conductivity (more than 200*) in ultrathin (~2-50 nm) MoS2 nanosheets after Li intercalation due to changes in band structure that reduce absorption upon intercalation and the injection of large amounts of free carriers. We also capture the first in situ optical observations of Li intercalation in MoS2 nanosheets, shedding light on the dynamics of the intercalation process and the associated spatial inhomogeneity and cycling induced structural defects. PMID- 26352297 TI - High-index faceted Ni3S2 nanosheet arrays as highly active and ultrastable electrocatalysts for water splitting. AB - Elaborate design of highly active and stable catalysts from Earth-abundant elements has great potential to produce materials that can replace the noble metal-based catalysts commonly used in a range of useful (electro)chemical processes. Here we report, for the first time, a synthetic method that leads to in situ growth of {210} high-index faceted Ni3S2 nanosheet arrays on nickel foam (NF). We show that the resulting material, denoted Ni3S2/NF, can serve as a highly active, binder-free, bifunctional electrocatalyst for both the hydrogen evolution reaction (HER) and the oxygen evolution reaction (OER). Ni3S2/NF is found to give ~100% Faradaic yield toward both HER and OER and to show remarkable catalytic stability (for >200 h). Experimental results and theoretical calculations indicate that Ni3S2/NF's excellent catalytic activity is mainly due to the synergistic catalytic effects produced in it by its nanosheet arrays and exposed {210} high-index facets. PMID- 26352296 TI - Binuclear Cu(A) Formation in Biosynthetic Models of Cu(A) in Azurin Proceeds via a Novel Cu(Cys)2His Mononuclear Copper Intermediate. AB - Cu(A) is a binuclear electron transfer (ET) center found in cytochrome c oxidases (CcOs), nitrous oxide reductases (N2ORs), and nitric oxide reductase (NOR). In these proteins, the Cu(A) centers facilitate efficient ET (kET > 104s-1) under low thermodynamic driving forces (10-90 mV). While the structure and functional properties of Cu(A) are well understood, a detailed mechanism of the incorporation of copper into the protein and the identity of the intermediates formed during the Cu(A) maturation process are still lacking. Previous studies of the Cu(A) assembly mechanism in vitro using a biosynthetic model Cu(A) center in azurin (Cu(A)Az) identified a novel intermediate X (Ix) during reconstitution of the binuclear site. However, because of the instability of Ix and the coexistence of other Cu centers, such as Cu(A)' and type 1 copper centers, the identity of this intermediate could not be established. Here, we report the mechanism of Cu(A) assembly using variants of Glu114XCuAAz (X = Gly, Ala, Leu, or Gln), the backbone carbonyl of which acts as a ligand to the Cu(A) site, with a major focus on characterization of the novel intermediate Ix. We show that Cu(A) assembly in these variants proceeds through several types of Cu centers, such as mononuclear red type 2 Cu, the novel intermediate Ix, and blue type 1 Cu. Our results show that the backbone flexibility of the Glu114 residue is an important factor in determining the rates of T2Cu -> Ix formation, suggesting that Cu(A) formation is facilitated by swinging of the ligand loop, which internalizes the T2Cu capture complex to the protein interior. The kinetic data further suggest that the nature of the Glu114 side chain influences the time scales on which these intermediates are formed, the wavelengths of the absorption peaks, and how cleanly one intermediate is converted to another. Through careful understanding of these mechanisms and optimization of the conditions, we have obtained Ix in ~80-85% population in these variants, which allowed us to employ ultraviolet-visible, electron paramagnetic resonance, and extended X-ray absorption fine structure spectroscopic techniques to identify the Ix as a mononuclear Cu(Cys)(2)(His) complex. Because some of the intermediates have been proposed to be involved in the assembly of native Cu(A), these results shed light on the structural features of the important intermediates and mechanism of Cu(A) formation. PMID- 26352298 TI - Re-wiring regulatory cell networks in immunity by galectin-glycan interactions. AB - Programs that control immune cell homeostasis are orchestrated through the coordinated action of a number of regulatory cell populations, including regulatory T cells, regulatory B cells, myeloid-derived suppressor cells, alternatively-activated macrophages and tolerogenic dendritic cells. These regulatory cell populations can prevent harmful inflammation following completion of protective responses and thwart the development of autoimmune pathology. However, they also have a detrimental role in cancer by favoring escape from immune surveillance. One of the hallmarks of regulatory cells is their remarkable plasticity as they can be positively or negatively modulated by a plethora of cytokines, growth factors and co-stimulatory signals that tailor their differentiation, stability and survival. Here we focus on the emerging roles of galectins, a family of highly conserved glycan-binding proteins in regulating the fate and function of regulatory immune cell populations, both of lymphoid and myeloid origins. Given the broad distribution of circulating and tissue-specific galectins, understanding the relevance of lectin-glycan interactions in shaping regulatory cell compartments will contribute to the design of novel therapeutic strategies aimed at modulating their function in a broad range of immunological disorders. PMID- 26352299 TI - Higher convection volume exchange with online hemodiafiltration is associated with survival advantage for dialysis patients: the effect of adjustment for body size. AB - Mortality remains high for hemodialysis patients. Online hemodiafiltration (OL HDF) removes more middle-sized uremic toxins but outcomes of individual trials comparing OL-HDF with hemodialysis have been discrepant. Secondary analyses reported higher convective volumes, easier to achieve in larger patients, and improved survival. Here we tested different methods to standardize OL-HDF convection volume on all-cause and cardiovascular mortality compared with hemodialysis. Pooled individual patient analysis of four prospective trials compared thirds of delivered convection volume with hemodialysis. Convection volumes were either not standardized or standardized to weight, body mass index, body surface area, and total body water. Data were analyzed by multivariable Cox proportional hazards modeling from 2793 patients. All-cause mortality was reduced when the convective dose was unstandardized or standardized to body surface area and total body water; hazard ratio (95% confidence intervals) of 0.65 (0.51 0.82), 0.74 (0.58-0.93), and 0.71 (0.56-0.93) for those receiving higher convective doses. Standardization by body weight or body mass index gave no significant survival advantage. Higher convection volumes were generally associated with greater survival benefit with OL-HDF, but results varied across different ways of standardization for body size. Thus, further studies should take body size into account when evaluating the impact of delivered convection volume on mortality end points. PMID- 26352301 TI - Association of oliguria with the development of acute kidney injury in the critically ill. AB - Urine output (UO) criterion may increase the sensitivity of the definition of acute kidney injury (AKI). We determined whether the empirically derived definition for oliguria (<0.5 ml/kg/h) is independently associated with adverse outcome. Data analysis included hourly recorded UO from the prospective, multicenter FINNAKI study conducted in 16 Finnish intensive care units. Confounder-adjusted association of oliguria of different severity and duration primarily with the development of AKI defined by creatinine criterion (Cr-AKI) or renal replacement therapy (RRT) was assessed. Secondarily, we determined the association of oliguria with 90-day mortality. Of the 1966 patients analyzed for the development of AKI, 454 (23.1%) reached this endpoint. Within this AKI cohort, 312 (68.7%) developed Cr-AKI, 21 (4.6%) commenced RRT without Cr-AKI, and 121 (26.7%) commenced RRT with Cr-AKI. Episodes of severe oliguria (<0.1 ml/kg/h) for more than 3 h were independently associated with the development of Cr-AKI or RRT. The shortest periods of consecutive oliguria independently associated with an increased risk for 90-day mortality were 6-12 h of oliguria from 0.3 to <0.5 ml/kg/h, over 6 h of oliguria from 0.1 to <0.3 ml/kg/h, and severe oliguria lasting over 3 h. Thus, our findings underlie the importance of hourly UO measurements.Kidney International advance online publication, 9 September 2015; doi:10.1038/ki.2015.269. PMID- 26352300 TI - Copy number variation analysis identifies novel CAKUT candidate genes in children with a solitary functioning kidney. AB - Copy number variations associate with different developmental phenotypes and represent a major cause of congenital anomalies of the kidney and urinary tract (CAKUT). Because rare pathogenic copy number variations are often large and contain multiple genes, identification of the underlying genetic drivers has proven to be difficult. Here we studied the role of rare copy number variations in 80 patients from the KIMONO study cohort for which pathogenic mutations in three genes commonly implicated in CAKUT were excluded. In total, 13 known or novel genomic imbalances in 11 of 80 patients were absent or extremely rare in 23,362 population controls. To identify the most likely genetic drivers for the CAKUT phenotype underlying these rare copy number variations, we used a systematic in silico approach based on frequency in a large data set of controls, annotation with publicly available databases for developmental diseases, tolerance and haploinsufficiency scores, and gene expression profile in the developing kidney and urinary tract. Five novel candidate genes for CAKUT were identified that showed specific expression in the human and mouse developing urinary tract. Among these genes, DLG1 and KIF12 are likely novel susceptibility genes for CAKUT in humans. Thus, there is a significant role of genomic imbalance in the determination of kidney developmental phenotypes. Additionally, we defined a systematic strategy to identify genetic drivers underlying rare copy number variations. PMID- 26352302 TI - The Medicines of Katherine, Duchess of Norfolk, 1463-71. AB - This article discusses the medicinal remedies consumed at the court of the Yorkist kings of England in the light of a lawsuit in the court of common pleas (edited in an appendix) between John Clerk, king's apothecary to Edward IV, and Katherine Neville, Duchess of Norfolk, over the partial non-payment of the apothecary's bills. It argues that the consumption of apothecaries' wares in large quantities was not merely a direct result of the excessive diet of the late medieval aristocracy, but in itself represented a facet of the conspicuous consumption inherent in the lifestyle of this particular social class. The remedies supplied by Clerk over a period of several years and listed in the legal record are set in the context of contemporary collections of medical recipes, particularly a 'dispensary' in the British Library's Harleian collection generally attributed to the king's apothecary. PMID- 26352303 TI - Thomas Willis, the Restoration and the First Works of Neurology. AB - This article provides a new consideration of how Thomas Willis (1621-75) came to write the first works of 'neurology', which was in its time a novel use of cerebral and neural anatomy to defend philosophical claims about the mind. Willis's neurology was shaped by the immediate political and religious contexts of the English Civil War and Restoration. Accordingly, the majority of this paper is devoted to uncovering the political necessities Willis faced during the Restoration of the English monarchy in 1660, with particular focus on the significance of Willis's dedication of his neurology and natural philosophy to the Archbishop of Canterbury, Gilbert Sheldon. Because the Restoration of Charles II brought only a semblance of order and peace, Willis and his allies understood the need for a coherent defense of the authority of the English church and its liturgy. Of particular importance to Sheldon and Willis (and to others in Sheldon's circle) were the specific ceremonies described in the Book of Common Prayer, a manual that directed the congregation to assume various postures during public worship. This article demonstrates that Willis's neurology should be read as an intervention in these debates, that his neurology would have been read at the time as an attempt to ground orthodox worship in the structure of the brain and nerves. The political necessities that helped to shape Willis's project also help us to better understand Willis's innovative insistence that philosophical statements about the mind should be formulated only after a comprehensive anatomical investigation of the brain and nerves. PMID- 26352304 TI - The American Hospital in Moscow: A Lesson in International Cooperation, 1917-23. AB - In its examination of American Medical Aid to Russia, this article shows how the best of intentions can have the potential to go horribly awry. It argues that the competing binary forces of international collaboration and goodwill versus political tensions and uncertainty combined to create an environment wherein actors and agents inhabited an ever changing and unpredictable international stage. Could American philanthropic organisations and individuals overcome political volatility, financial restrictions and ideological barriers? Just what would it take to establish an American hospital in Moscow, the Bolshevik seat of power? The attempt to establish the hospital proved to be an exercise in patience, persistence and prudence (although not always in equal measure). This article shows that international cooperation, while undoubtedly complicated, was certainly possible. The flow of information, materiel and personnel between the United States, Germany and Russia proved that good intentions, trust and a will to help others were valued. The history of American Medical Aid to Russia also demonstrates that the Quaker role of facilitator and interlocutor was vital in establishing a relationship of trust between Soviet Russia and the United States. This article discusses the difficulties that philanthropic organisations faced when navigating the choppy international waters of the early 1920s and highlights the rewards of successfully doing this. It argues that basic human relationships and trust were just as, if not sometimes more, important than ideology in determining the tenor of early US-Soviet relations. PMID- 26352305 TI - 'Chronophilia': Entries of Erotic Age Preference into Descriptive Psychopathology. AB - A scientific nomenclature of erotic age preferences informed the mid- through late nineteenth century joint appearance of homosexuality and sexual abuse of minors on the medico-legal scene. Yet, even in the twenty-first century, legal, psychiatric and culture-critical dimensions of related terms are rarely cleanly distinguished. Review of primary sources shows the ongoing Western suspension of notions of 'sick desire', alongside and beyond the medicalisation of homosexuality, between metaphor, legal interdiction and postulated psychopathology. Virtually all early attention to erotic age preference occurred in the context of emergent attention to erotic gender preference. Age of attraction and age difference centrally animate modern homosexuality's pre-modern past; its earliest psychiatric nomenclature and typologies (1844-69); its early aetiologies stipulating degrees of sexual differentiation (1890 s); its concomitant sub-classification (1896-1914); its earliest psychophysiological tests (1950s); and, finally, its post-psychiatric, social scientific typologies (1980s). Several identifications of 'paedophilia' were seen throughout the 1890 s but as a trope it gained cultural momentum only during, and as a seemingly intriguing corollary of, the progressive depsychiatricisation of homosexuality across the Anglo-European world (late 1950s through 1980s). Early twentieth century sources varied in having it denote (1) a distinct perversion, thus possible 'complication' of sexual inversion (2) a discrete corollary of psychosexual differentiation akin to gender preference (3) a distinct subtype of fetishism, thus a likely imprint of early seduction (4) a more intricate expression of erotic symbolism or psychosexual complex or (5) a taste answering to culture, a lack of it, or a libertine disregard for it. PMID- 26352306 TI - The History of Mental Health Services in Modern England: Practitioner Memories and the Direction of Future Research. AB - Writing the recent history of mental health services requires a conscious departure from the historiographical tropes of the nineteenth and twentieth centuries which have emphasised the experience of those identified (and legally defined) as lunatics and the social, cultural, political, medical and institutional context of their treatment. A historical narrative structured around rights (to health and liberty) is now complicated by the rise of new organising categories such as 'costs', 'risks', 'needs' and 'values'. This paper, drawing on insights from a series of witness seminars attended by historians, clinicians and policymakers, proposes a programme of research to place modern mental health services in England and Wales in a richer historical context. Historians should recognise the fragmentation of the concepts of mental illness and mental health need, acknowledge the relationship between critiques of psychiatry and developments in other intellectual spheres, place the experience of the service user in the context of wider socio-economic and political change, understand the impacts of the social perception of 'risk' and of moral panic on mental health policy, relate the politics of mental health policy and resources to the general determinants of institutional change in British central and local government, and explore the sociological and institutional complexity of the evolving mental health professions and their relationships with each other and with their clients. While this is no small challenge, it is perhaps the only way to avoid the perpetuation of 'single-issue mythologies' in describing and accounting for change. PMID- 26352316 TI - Health Hazards of Fashion: A Review of Bata Shoe Museum's Exhibit, Fashion Victims: The Pleasures and Perils of Dress in the 19th Century. PMID- 26352322 TI - SUSAC SYNDROME. AB - PURPOSE: To describe an atypical presentation of Susac syndrome. METHODS: Observational case report. RESULTS: A 44-year-old man with no significant medical history presented with inferonasal visual field loss in his left eye of several months of duration. He was found to have bilateral migratory arteritis with focal areas of arteriolar occlusion in both eyes and peripheral ischemia superotemporally in his left eye. An extensive hematologic workup was negative for autoimmune disease or coagulopathy. Magnetic resonance imaging with contrast of his brain revealed a hyperintense lesion in the splenium of the corpus callosum. Auditory testing was significant for nonspecific high-frequency hearing loss in the right ear. Given the full clinical picture, a diagnosis of Susac syndrome was made. CONCLUSION: Susac syndrome is a multisystemic, immune-mediated occlusive endotheliopathy characterized by the clinical triad of encephalopathy, branch retinal artery occlusions, and hearing loss. However, patients may present with varying degrees of this triad; thus, there should be a high index of suspicion in patients presenting with multiple artery occlusions or multifocal arteritis. PMID- 26352323 TI - VANISHING RETINAL DETACHMENT. AB - PURPOSE: The purpose of this report is to describe a case of rhegmatogenous retinal detachment in the setting of chronic kidney disease that exhibited complete retinal reattachment after serial hemodialysis. METHODS: Retrospective case report. RESULTS: A 58-year-old woman with acute vision loss was found to have a macula-involving rhegmatogenous retinal detachment. Due to chronic kidney disease, she continued with routinely scheduled hemodialysis for 1 week until surgical clearance was obtained. Preoperative examination revealed complete reattachment of the retina with a persistent retinal tear. Barrier laser was applied to the tear and the retina remained attached until the most recent follow up 8 months later. The workup of alternate etiologies was unrevealing. CONCLUSION: This case describes a temporal association between hemodialysis and resolution of subretinal fluid due to rhegmatogenous retinal detachment. A potential causal linkage is suggested based on shifting fluid dynamics associated with hemodialysis. A shift in treatment paradigm is not advised. PMID- 26352324 TI - PRESUMED POSTERIOR UVEITIS RELATED TO EHRLICHIA EXPOSURE. AB - PURPOSE: To describe a case of posterior uveitis with retinal vasculitis related to Ehrlichia exposure. PATIENTS AND METHODS: Single case report of a 68-year-old woman with posterior uveitis, steroid-induced glaucoma, and retinal holes. RESULTS: Ehrlichia titers were elevated 4-fold (1:256; normal <1:64) with an otherwise normal laboratory workup. The patient's cystoid macular edema responded to sub-Tenon's triamcinolone and oral doxycycline. CONCLUSION: To our knowledge, this is the first case of posterior uveitis associated with Ehrlichia reported in humans. PMID- 26352326 TI - Enhanced molecular dynamics sampling of drug target conformations. AB - Computational docking and virtual screening are two main important methods employed in structure-based drug design. Unlike the traditional approach that allows docking of a flexible ligand against a handful of receptor structures, receptor flexibility has now been appreciated and increasingly incorporated in computer-aided docking. Using a diverse set of receptor conformations increases the chances of finding potential drugs and inhibitors. Molecular dynamics (MD) is greatly useful to generate various receptor conformations. However, the diversity of the structures of the receptor, which is usually much larger than the ligand, depends on the sampling efficiency of MD. Enhanced sampling methods based on accelerated molecular dynamics (aMD) can alleviate the sampling limitation of conventional MD and aid in representation of the phase space to a much greater extent. RaMD-db, a variant of aMD that applies boost potential to the rotatable dihedrals and non-bonded diffusive degrees of freedom has been proven to reproduce the equilibrium properties more accurately and efficiently than aMD. Here, we discuss recent advances in the aMD methodology and review the applicability of RaMD-db as an enhanced sampling method. RaMD-db is shown to be able to generate a broad distribution of structures of a drug target, Cyclophilin A. These structures that have never been observed previously in very long conventional MD can be further used for structure-based computer-aided drug discovery, and docking, and thus, in the identification and design of potential novel inhibitors. PMID- 26352328 TI - How Accurately Can Extended X-ray Absorption Spectra Be Predicted from First Principles? Implications for Modeling the Oxygen-Evolving Complex in Photosystem II. AB - First principle calculations of extended X-ray absorption fine structure (EXAFS) data have seen widespread use in bioinorganic chemistry, perhaps most notably for modeling the Mn4Ca site in the oxygen evolving complex (OEC) of photosystem II (PSII). The logic implied by the calculations rests on the assumption that it is possible to a priori predict an accurate EXAFS spectrum provided that the underlying geometric structure is correct. The present study investigates the extent to which this is possible using state of the art EXAFS theory. The FEFF program is used to evaluate the ability of a multiple scattering-based approach to directly calculate the EXAFS spectrum of crystallographically defined model complexes. The results of these parameter free predictions are compared with the more traditional approach of fitting FEFF calculated spectra to experimental data. A series of seven crystallographically characterized Mn monomers and dimers is used as a test set. The largest deviations between the FEFF calculated EXAFS spectra and the experimental EXAFS spectra arise from the amplitudes. The amplitude errors result from a combination of errors in calculated S0(2) and Debye-Waller values as well as uncertainties in background subtraction. Additional errors may be attributed to structural parameters, particularly in cases where reliable high-resolution crystal structures are not available. Based on these investigations, the strengths and weaknesses of using first-principle EXAFS calculations as a predictive tool are discussed. We demonstrate that a range of DFT optimized structures of the OEC may all be considered consistent with experimental EXAFS data and that caution must be exercised when using EXAFS data to obtain topological arrangements of complex clusters. PMID- 26352329 TI - Water adsorption in SAPO-34: elucidating the role of local heterogeneities and defects using dispersion-corrected DFT calculations. AB - The chabazite-type silicoaluminophosphate SAPO-34 is a promising adsorbent for applications in thermal energy storage using water adsorption-desorption cycles. In order to develop a microscopic understanding of the impact of local heterogeneities and defects on the water adsorption properties, the interaction of different models of SAPO-34 with water was studied using dispersion-corrected density-functional theory (DFT-D) calculations. In addition to SAPO-34 with isolated silicon atoms, the calculations considered models incorporating two types of heterogeneities (silicon islands, aluminosilicate domains), and two defect-containing (partially and fully desilicated) systems. DFT-D optimisations were performed for systems with small amounts of adsorbed water, in which all H2O molecules can interact with framework protons, and systems with large amounts of adsorbed water (30 H2O molecules per unit cell). At low loadings, the host-guest interaction energy calculated for SAPO-34 with isolated Si atoms amounts to approximately -90 kJ mol(-1). While the presence of local heterogeneities leads to the creation of some adsorption sites that are energetically slightly more favourable, the interaction strength is drastically reduced in systems with defects. At high water loadings, energies in the range of -70 kJ mol(-1) are obtained for all models. The DFT-D interaction energies are in good agreement with experimentally measured heats of water adsorption. A detailed analysis of the equilibrium structures was used to gain insights into the binding modes at low coverages, and to assess the extent of framework deprotonation and changes in the coordination environment of aluminium atoms at high water loadings. PMID- 26352327 TI - Concise Review: Pluripotent Stem Cell-Derived Cardiac Cells, A Promising Cell Source for Therapy of Heart Failure: Where Do We Stand? AB - Heart failure is still a major cause of hospitalization and mortality in developed countries. Many clinical trials have tested the use of multipotent stem cells as a cardiac regenerative medicine. The benefit for the patients of this therapeutic intervention has remained limited. Herein, we review the pluripotent stem cells as a cell source for cardiac regeneration. We more specifically address the various challenges of this cell therapy approach. We question the cell delivery systems, the immune tolerance of allogenic cells, the potential proarrhythmic effects, various drug mediated interventions to facilitate cell grafting and, finally, we describe the pathological conditions that may benefit from such an innovative approach. As members of a transatlantic consortium of excellence of basic science researchers and clinicians, we propose some guidelines to be applied to cell types and modes of delivery in order to translate pluripotent stem cell cardiac derivatives into safe and effective clinical trials. PMID- 26352325 TI - Characterization of glucose-related metabolic pathways in differentiated rat oligodendrocyte lineage cells. AB - Although oligodendrocytes constitute a significant proportion of cells in the central nervous system (CNS), little is known about their intermediary metabolism. We have, therefore, characterized metabolic functions of primary oligodendrocyte precursor cell cultures at late stages of differentiation using isotope-labelled metabolites. We report that differentiated oligodendrocyte lineage cells avidly metabolize glucose in the cytosol and pyruvate derived from glucose in the mitochondria. The labelling patterns of metabolites obtained after incubation with [1,2-(13)C]glucose demonstrated that the pentose phosphate pathway (PPP) is highly active in oligodendrocytes (approximately 10% of glucose is metabolized via the PPP as indicated by labelling patterns in phosphoenolpyruvate). Mass spectrometry and magnetic resonance spectroscopy analyses of metabolites after incubation of cells with [1-(13)C]lactate or [1,2 (13)C]glucose, respectively, demonstrated that anaplerotic pyruvate carboxylation, which was thought to be exclusive to astrocytes, is also active in oligodendrocytes. Using [1,2-(13)C]acetate, we show that oligodendrocytes convert acetate into acetyl CoA which is metabolized in the tricarboxylic acid cycle. Analysis of labelling patterns of alanine after incubation of cells with [1,2 (13)C]acetate and [1,2-(13)C]glucose showed catabolic oxidation of malate or oxaloacetate. In conclusion, we report that oligodendrocyte lineage cells at late differentiation stages are metabolically highly active cells that are likely to contribute considerably to the metabolic activity of the CNS. PMID- 26352330 TI - Is it possible folic acid reduce anorectal malformations ethylenethiourea induced in rats? AB - PURPOSE: To investigate the effect of folic acid (FA) in an experimental model of anorectal malformations (ARMs) ethylenethiourea (ETU) induced. METHODS: Eight female Wistar rats were divided randomly in two groups. Group A - ETU; Group B - FA+ETU; Dams from group B received daily, since two weeks before pregnancy to the end of pregnancy, FA (50mg/kg) by gavage. Dams from groups A and B, received 1% ETU (125 mk/kg) by gavage on gestational day (GD) 11. Their fetuses were harvested by cesarean section on GD21 and were examined looking for ARMs. The thickness of anal stratified squamous epithelium (ASSE) and intestinal epithelium (IE) were analyzed. p < 0.05*. RESULTS: One hundred and one embryos were harvested. The number of embryos; number of ARMs; mean statistical % (+/- SD) were determined to be, respectively: ETU - 49 [30;65% (+/- 24%)] versus FA+ETU - 52 [1;02% (+/- 3%)] (p = 0.025). AMRs were significantly lower in FA+ETU group than in ETU group (p = 0.025). The thickness (um) of ASSE (+/- SD) and IE (+/- SD) were measured, respectively: ETU - [27.75 (+/- 0.56) and 18.88 (+/- 0.93)] versus FA+ETU - [28.88 (+/- 0.61) and 21.11 (+/- 0.16)] (p = 0.001). The thickness of IE was significantly enlarged when FA was given (p=0.001). CONCLUSION: Folic acid reduces the number and enlarged the IE of ARMs ETU induced. PMID- 26352331 TI - Does dexamethasone act in neuropeptides SP and CGRP in neurogenic inflammation of the skin? An experimental study. AB - PURPOSE: To investigate the neuropeptides substance P (SP) and calcitonin gene related peptide (CGRP) after subcutaneous injection of dexamethasone prior to skin incision in rats. METHODS: Twenty seven Wistar-EPM-1 rats were randomly divided into three groups. The sham group (SG) of rats was injected with 0.9 % saline. The second group (Dexa) was injected with 1.0 mg/kg dexamethasone, and the third group (Dexa+) was injected with 10.0 mg/kg dexamethasone. In all groups, the three subcutaneous injections were performed 30 minutes prior to the surgical skin incision and tissue collection. SP and CGRP (15 kDa pro-CGRP and 5 kDa CGRP) were quantified by Western Blotting. RESULTS: No statistically significant differences (p>0.05) were found in pro-CGRP, CGRP and SP values in all three groups. CONCLUSION: The anti-inflammatory effect of dexamethasone did not occur when the substance P and calcitonin gene-related peptide levels were altered during the neurogenic inflammation process of skin wound healing in rats. PMID- 26352332 TI - Penile reconstruction using mesenchymal stem cells. AB - PURPOSE: To compare the reconstruction of corpus cavernosum segments when seeded with mesenchymal stem cells and when stem cells are infused intravenously. METHODS: Sixteen New Zealand rabbits were submitted to reconstruction of the corpus cavernosum and distributed in Group A - decellularized matrices, Group B - decellularized matrices seeded with mesenchymal stem cells Group C - decellularized matrices submitted to intravenous infusion of mesenchymal stem cells. The mesenchymal stem cells were obtained by bone marrow aspiration. The venous filling aspect of the distal end of the corpus cavernosum was evaluated and the specimens were submitted to histological analisis and to immunohistochemistry. Cavernosometry was done in one animal of each group. RESULTS: Three animals on B and three animals on C presented full filling of distal end of the corpus cavernosum. No animals in A presented filling of the distal end of corpus cavernosum. At cavernosometry the animal on B attained 50 cmH2O, on C 110 cmH2O and on A 20 cmH2O. Trabeculae forming cavernous sinuses were found in groups B and C. CONCLUSION: The reconstruction of corpus cavernosum using descellularized matrices and mesenchymal stem cells, either by intravenous injection or directly seeded is possible, with growth of corpus cavernosum-like tissue. PMID- 26352333 TI - Laparoscopic correction of experimentally induced diaphragmatic rupture in dogs. AB - PURPOSE: To describe the dog as a model for studying laparoscopic correction of experimental diaphragmatic ruptures. METHODS: Five male dogs were used in this study. Under laparoscopic approach, a defect of 7 cm was created on the left ventral insertion of the diaphragm. Fourteen days after this procedure, the abdomen was explored using laparoscopic access and the diaphragmatic defect was corrected with intracorporeal suture. The dislocated organs, surgical time, and suturing time were recorded. Analgesia and clinical condition were monitored during the postoperative period. RESULTS: All animals recovered well from the diaphragmatic rupture creation. After 14 days, abdominal organs (liver, spleen, omentum and/or intestine) were found inside the thoracic cavity in all animals. It was possible to reposition the organs and suture the defect by laparoscopic access in three animals. These animals showed excellent postoperative recovery. It was not possible to reposition the liver safely when it was friable. CONCLUSIONS: Laparoscopic creation of diaphragmatic rupture in dogs is feasible. Dogs are a good model for training and studying the correction of experimentally created diaphragmatic rupture by the laparoscopic approach. A friable liver is a complicating factor that should be taken into account. Animals submitted to laparoscopic correction showed excellent postoperative recovery. PMID- 26352334 TI - Study on the effect of black cumin (Nigella sativa Linn.) on experimental renal ischemia-reperfusion injury in rats. AB - PURPOSE: To evaluate the effect of Black cumin (Nigella sativa Linn.) pre treatment on renal ischemia/reperfusion (I/R) induced injury in the rats. METHODS: A total of 40 male Wistar rats were randomly allocated into five equal groups including Sham, I/R model and three I/R+ Black cumin (0.5, 1 and 2%) treated groups. I/R groups' kidneys were subjected to 60 min of global ischemia at 37 degrees C followed by 24 h of reperfusion. At the end of reperfusion period, the rats were euthanized. Superoxide dismutase, catalase and glutathione peroxidase activities as well as reduced glutathione and renal malondialdehyde contents were determined in renal tissues. Kidney function tests and histopathological examination were also performed. RESULTS: High serum creatinine, blood urea nitrogen and uric acid as well as malondialhehyde (MDA) levels, and low antioxidant enzyme activities were observed in I/R rats compared to the sham rats. Pre-treatment with Black cumin for three weeks prior to IR operation improved renal function and reduced I/R induced renal inflammation and oxidative injury. These biochemical observations were supported by histopathological test of kidney sections. CONCLUSION: Black cumin significantly prevented renal ischemia/reperfusion induced functional and histological injuries. PMID- 26352335 TI - Intra and postoperative evaluations of microcirculation and micro-rheological parameters in a rat model of musculocutaneous flap ischemia-reperfusion. AB - PURPOSE: To examine how the ischemia-reperfusion injury of latissimus dorsi cutaneous maximus (LDCM) musculocutaneous flap affects the microcirculatory (flap's skin surface) and hemorheological parameters, and whether an intraoperative deterioration would predictively suggest flap failure in the postoperative period. METHODS: Ten healthy male rats were subjected to the study. In Group I the left flap was sutured back after 2-hour, while the contralateral side was right after its elevation. In Group II the same technique was applied, but the pedicle of the left flap was atraumatically clamped for 2-hour. The contralateral side was left intact. On the flap skin surface laser Doppler tissue flowmetry measurements were done before and after and during the protocols applied in the groups. Microcirculatory and hemorheological examinations were done postoperatively. RESULTS: The microcirculatory parameters significantly decreased during immobilization and ischemia. Afterwards, all the regions showed normalization. In the retrospective analysis there was a prominent difference between the microcirculatory parameters of necrotic and survived flap during the early postoperative days (1-3) in Group II. Erythrocyte aggregation and deformability showed only slight differences. CONCLUSIONS: Two-hour ischemia and reperfusion caused deterioration in latissimus dorsi-cutaneous maximus flap microcirculation. Predicting the possible postoperative complication, the intraoperative laser Doppler measurement can be informative. PMID- 26352336 TI - Adjustable inspiratory occlusion valve in experimental bronchopleural fistula. A new therapeutic perspective. AB - PURPOSE: To assess the efficacy of an adjustable inspiratory occlusion valve in experimental bronchopleural fistula during mechanical ventilation. METHODS: We studied six mechanically ventilated pigs in a surgically created, reproducible model of bronchopleural fistula managed with mechanical ventilation and water sealed thoracic drainage. An adjustable inspiratory occlusion valve was placed between the thoracic drain and the endotracheal tube. Hemodynamic data, capnography and blood gases were recorded before and after the creation of the bronchopleural fistula as well as after every adjustment of the inspiratory occlusion valve. RESULTS: When compared with the standard water-sealed drainage treatment, the use of an adjustable inspiratory occlusion valve improved the alveolar tidal volume and reduced bronchopleural air leak (p<0.001), without hemodynamic compromise when compared with conventional water sealed drainage. CONCLUSION: The use of an adjustable inspiratory occlusion valve improved the alveolar tidal volume, reduced alveolar leak, in an experimental reproducible model of bronchopleural fistula, without causing any hemodynamic derangements when compared with conventional water sealed drainage. PMID- 26352337 TI - Copaiba oil effect on induced fecal peritonitis in rats. AB - PURPOSE: To evaluate the effects of copaiba oil as a prophylactic and/or therapeutic substance on survival of rats subjected to cecal ligation and puncture, describing histopathological and oxidative stress findings. METHODS: Forty rats (Ratus norvegicus) were distributed into five study groups (N=8): Sham group (ShG): normal standard animals; Sepse group (SepG): submitted a cecal ligation and puncture (CLP); Pre group (PreG): administered copaiba oil once daily by subcutaneous injection for five days before carrying out CLP; Post CLP group (PostG): administered copaiba oil once daily by subcutaneous injection from the first day of CLP until death by sepsis; and Pre/Post group (Pre/PostG): administered copaiba oil once daily by subcutaneous injection for five days before carrying out CLP and from the first day of CLP until de death by sepsis. After the death of the animals, blood was collected for assessment of oxidative stress and histological analysis were performed. The Kaplan-Meier curves of surviving time were realized. RESULTS: Survival analysis demonstrated that animals treated with copaiba oil prior to the execution of the CLP (PreG and Pre/Post groups) had longer survival compared to the sepsis group (p<0.0001) whereas animals receiving copaiba only after the completion of CLP (PostG) showed no statistically significant difference compared to the sepsis group. However, when comparing the two groups in which was administered copaiba previously (PreG and Pre/PostG groups), there was no statistical significance between the groups (p=0.4672). There was no statistical difference between histopathological findings or the levels of oxidative stress. CONCLUSION: Prophylactic subcutaneous administration of copaiba increases survival of rats subjected to severe sepsis by cecal ligation and puncture. PMID- 26352338 TI - Does a small size needle puncture cause intervertebral disc changes? AB - PURPOSE: Small size needles have been regularly used for intradiscal injection of innocuous/potential therapeutic compounds in experimental conditions, but also in clinic procedures, such as discography. Our aim was to investigate if a 30-gauge needle could trigger observable changes on intact intervertebral discs. We compared these effects to those induced by a large size needle (21-gauge), a well known intervertebral disc degenerative model based on needle puncture. METHODS: Coccygeal intervertebral discs (Co8-9) of adult male Wistar rats were punctured with a 21-gauge needle, while the coccygeal levels Co7-8 and Co9-10 remained intact. The 30-gauge needle was used to inject a safe volume of saline (2 ul) on both intact (Co9-10) and punctured (Co8-9) discs. MRI and histological score were performed at 2, 15 and 42 days after procedure. RESULTS: MRI analyses revealed significant reduction on signal intensity of 21-gauge punctured discs. Intact discs which received a saline injection through a 30-gauge needle also revealed significant alterations in the MRI signal when compared with control discs. No histological changes were observed in the intact saline injected discs at any time analyzed. CONCLUSION: Since significant intervertebral image changes were observed with a 30-gauge needle, cautious interpretation of the pharmacological inoculation findings is required. PMID- 26352339 TI - The Glasgow Prognostic Score. An useful tool to predict survival in patients with advanced esophageal squamous cell carcinoma. AB - PURPOSE: To evaluate the usefulness of the Glasgow Prognostic Score (GPS) in patients with esophageal carcinoma (EC). METHODS: A total of 50 patients with EC were analyzed for GPS, nutritional and clinicopathologic parameters. Patients with CRP <= 1.0mg/L and albumin >= 3.5mg/L were considered as GPS = 0. Patients with only CRP increased or albumin decreased were classified as GPS = 1 and patients with CRP > 1.0mg/L and albumin < 3.5mg/L were considered as GPS = 2. RESULTS: GPS of 0, 1 and 2 were observed in seven, 23 and 20 patients, respectively. A significant inverse relationship was observed between GPS scores and the survival rate. The survival rate was greatest in patients with GPS = 0 and significantly higher than those from patients with GPS = 1 and GPS = 2. Minimum 12-month survival was observed in 71% patients with GPS = 0 and in 30% patients with GPS = 1. None of the patients with GPS = 2 survived for 12 months. A significant relationship between CRP or albumin individually and the survival rate was observed. No significant relationship among nutritional, clinic pathological parameters and survival was found. CONCLUSION: Glasgow Prognostic Score is an useful tool to predict survival in patients with esophageal carcinoma. PMID- 26352340 TI - Copper-mediated stereospecific C-H oxidative sulfenylation of terminal alkenes with disulfides. AB - A copper and iodine-mediated C-H oxidative sulfenylation of olefins with diaryl disulfides has been developed for the stereospecific synthesis of vinyl thioether. With the combination of Cu(OTf)2 and I2, a variety of terminal alkenes underwent oxidative coupling reaction with various diaryl disulfides successfully to afford the corresponding E-vinyl sulfides in moderate to good yields. PMID- 26352341 TI - Facets of Dispositional Mindfulness and Health Among College Students. AB - OBJECTIVE: The purpose of the current study was to examine the relationship between the facets of trait mindfulness with psychological and physical health while controlling for health behaviors in college students. PARTICIPANTS: 310 students from a small, private college in the Northeastern United States. OUTCOME MEASURES: Students completed self-report measures, including the Perceived Stress Scale (PSS-14), the Five Facet Mindfulness Questionnaire (FFMQ), Medical Outcomes Short-Form Health Survey (SF-36), and the Rutgers Alcohol Problems Index (RAPI). RESULTS: After controlling for other health behaviors, the observation facet of mindfulness was negatively associated with physical health. Both acting with awareness and nonjudging facets were positively associated with emotional well being. For social functioning, nonjudging was a significant positive facet for this domain of health. CONCLUSIONS: Tailoring mindfulness-based interventions to enhance these facets may be beneficial to young adults. PMID- 26352342 TI - Training in minimally invasive surgery in urology: European Association of Urology/International Consultation of Urological Diseases consultation. AB - OBJECTIVES: To describe the progress being made in training for minimally invasive surgery (MIS) in urology. METHODS: A group of experts in the field provided input to agree on recommendations for MIS training. A literature search was carried out to identify studies on MIS training, both in general and specifically for urological procedures. RESULTS: The literature search showed the rapidly developing options for e-learning, box and virtual training, and suggested that box training is a relatively cheap and effective means of improving laparoscopic skills. Development of non-technical skills is an integral part of surgical skills training and should be included in training curricula. The application of modular training in surgical procedures showed more rapid skills acquisition. Training curricula for MIS in urology are being developed in both the USA and Europe. CONCLUSION: Training in MIS has shifted from 'see-one-do one-teach-one' to a structured learning, from e-learning to skills laboratory and modular training settings. PMID- 26352343 TI - Physicochemical and Gelatinization Properties of Starches Separated from Various Rice Cultivars. AB - Morphological, viscoelastic, hydration, pasting, and thermal properties of starches separated from 10 different rice cultivars were investigated. Upon gelatinization, the G' values of the rice starch pastes ranged from 37.4 to 2057 Pa at 25 degrees C, and remarkably, the magnitude depended on the starch varieties. The rheological behavior during gelatinization upon heating brought out differences in onset in G' and degree of steepness. The cultivar with high amylose content (Goami) showed the lowest critical strain (gamma(c)), whereas the cultivars with low amylose content (Boseokchal and Shinseonchal) possessed the highest gamma(c). The amylose content in rice starches affected their pasting properties; the sample possessing the highest amylose content showed the highest final viscosity and setback value, whereas waxy starch samples displayed low final viscosity and setback value. The onset gelatinization temperatures of the starches from 10 rice cultivars ranged between 57.9 and 64.4 degrees C. The amylose content was fairly correlated to hydration and pasting properties of rice starches but did not correlate well with viscoelastic and thermal characteristics. The combined analysis of hydration, pasting, viscoelastic, and thermal data of the rice starches is useful in fully understanding their behavior and in addressing the processability for food applications. PRACTICAL APPLICATION: Rice flour has potential applications in various food products. The physicochemical properties of rice flour are dependent on its variety, which affects the quality of the final products. In this study, the combined analysis including hydration, pasting, viscoelastic, and thermal properties of rice flour could afford information for preparing a particular product such as bread and noodle. PMID- 26352344 TI - A Balancing Act: Stability versus Reactivity of Mn(O) Complexes. AB - A large class of heme and non-heme metalloenzymes utilize O2 or its derivatives (e.g., H2O2) to generate high-valent metal-oxo intermediates for performing challenging and selective oxidations. Due to their reactive nature, these intermediates are often short-lived and very difficult to characterize. Synthetic chemists have sought to prepare analogous metal-oxo complexes with ligands that impart enough stability to allow for their characterization and an examination of their inherent reactivity. The challenge in designing these molecules is to achieve a balance between their stability, which should allow for their in situ characterization or isolation, and their reactivity, in which they can still participate in interesting chemical transformations. This Account focuses on our recent efforts to generate and stabilize high-valent manganese-oxo porphyrinoid complexes and tune their reactivity in the oxidation of organic substrates. Dioxygen can be used to generate a high-valent Mn(V)(O) corrolazine (Mn(V)(O)(TBP8Cz)) by irradiation of Mn(III)(TBP8Cz) with visible light in the presence of a C-H substrate. Quantitative formation of the Mn(V)(O) complex occurs with concomitant selective hydroxylation of the benzylic substrate hexamethylbenzene. Addition of a strong H(+) donor converted this light/O2/substrate reaction from a stoichiometric to a catalytic process with modest turnovers. The addition of H(+) likely activates a transient Mn(V)(O) complex to achieve turnover, whereas in the absence of H(+), the Mn(V)(O) complex is an unreactive "dead-end" complex. Addition of anionic donors to the Mn(V)(O) complex also leads to enhanced reactivity, with a large increase in the rate of two-electron oxygen atom transfer (OAT) to thioether substrates. Spectroscopic characterization (Mn K-edge X-ray absorption and resonance Raman spectroscopies) revealed that the anionic donors (X(-)) bind to the Mn(V) ion to form six coordinate [Mn(V)(O)(X)](-) complexes. An unusual "V-shaped" Hammett plot for the oxidation of para-substituted thioanisole derivatives suggested that six coordinate [Mn(V)(O)(X)](-) complexes can act as both electrophiles and nucleophiles, depending on the nature of the substrate. Oxidation of the Mn(V)(O) corrolazine resulted in the in situ generation of a Mn(V)(O) pi-radical cation complex, [Mn(V)(O)(TBP8Cz(*+))](+), which exhibited more than a 100-fold rate increase in the oxidation of thioethers. The addition of Lewis acids (LA; Zn(II), B(C6F5)3) to the closed-shell, diamagnetic Mn(V)(O)(TBP8Cz) stabilized a paramagnetic valence tautomer Mn(IV)(O)(TBP8Cz(*+))(LA), which was characterized as a second pi-radical cation complex by NMR, EPR, UV-vis, and high resolution cold spray ionization MS. The Mn(IV)(O)(TBP8Cz(*+))(LA) complexes are able to abstract H(*) from phenols and exhibit a rate enhancement of up to ~100-fold over the parent Mn(V)(O) valence tautomer. In contrast, a large decrease in rate is observed for OAT for the Mn(IV)(O)(TBP8Cz(*+))(LA) complexes. The rate enhancement for hydrogen atom transfer (HAT) may derive from the higher redox potential for the pi-radical cation complex, while the large rate decrease seen for OAT may come from a decrease in electrophilicity for an Mn(IV)(O) versus Mn(V)(O) complex. PMID- 26352345 TI - Synthesis and reactivity of indium(I) 1-carba-closo-undecachlorododecaborate. AB - The arene-solvated indium(I) species [In(C7H8)3][CHB11Cl11] (1) and [In(C6H5Br)1.5][CHB11Cl11] (2) were obtained by a redox reaction involving the silver salt Ag[CHB11Cl11] and indium powder at 80 degrees C in a toluene or bromobenzene solution. These thermally stable compounds react with triphenylphosphine and the N-heterocyclic carbene 1,3-bis(2,6 diisopropylphenyl)imidazol-2-ylidene under reduction of indium(I) to indium metal and oxidation of the ligands to phosphonium and imidazolium cations contrary to the more commonly observed disproportionation reactions. The presence of 2 equiv of carbene led to deprotonation of the anion to give the dianion [CB11Cl11](2-). Interactions of In(+) with soft donor ligands such as phosphines, olefins, alkynes, and aromatics are weak, and a crystalline solid was only obtained with the nonvolatile phosphinoacetylene Mes2PC=CPh (Mes = 2,4,6-Me3C6H2). The structure of this compound displays In...C interactions involving the triple bond and the pi system of one mesityl group but no In...P contact. Solutions of 2 in fluorobenzene also showed moderate activity as the catalyst for intramolecular hydroamination of primary and secondary aminopentenes. The new compounds were characterized by multinuclear NMR spectroscopy and X-ray diffraction for compounds 1, 2, and 4-6. PMID- 26352346 TI - Effect of Different Contact Materials on Approximal Caries Detection by Laser Fluorescence and Light-Emitting Diode Devices. AB - OBJECTIVE: The aim of this in vitro study was to investigate the influence of the adjacent tooth surface on pen type laser fluorescence (LFpen) and light-emitting diode (LED) device readings in detecting approximal caries lesions in permanent teeth. BACKGROUND DATA: Early detection of noncavitated dental caries is important, because disease progression can be easily halted at this stage with certain applications, such as fluoride therapy, antibacterial therapy, dietary changes, or low-intensity laser irradiation. MATERIALS AND METHODS: A total of 87 permanent molars with 156 approximal surfaces were assessed with LED- and LF based devices in contact with sound tooth surfaces (the control group) as well as approximal amalgam, composite, zirconia, and full ceramic restorations. All teeth were assessed once by one trained examiner. After the LF and LED assessments, the teeth were histologically evaluated using stereomicroscopy as the gold standard. The sensitivity, specificity, accuracy, and area under the receiver operating characteristics (ROC) curve were calculated according to the appropriate thresholds (T1, sound surface or enamel caries; T2, dentin caries). RESULTS: For the LFpen device, higher sensitivity and accuracy was found when the adjacent surface was sound at the T1 threshold and no significant differences were found among accuracy at the T2 threshold. For the LED-based device, no significant differences were found among sensitivities at the T1 threshold. At the T2 threshold, specificity was higher when the adjacent tooth had a zirconia restoration. CONCLUSIONS: It was found that both devices could be used effectively for evaluating approximal surfaces with adjacent restored teeth, regardless of the different kinds of restorative materials. PMID- 26352347 TI - Low liquid flows - an important aspect in medical technology. PMID- 26352348 TI - Flow variability and its physical causes in infusion technology: a systematic review of in vitro measurement and modeling studies. AB - Infusion therapy is medically and technically challenging and frequently associated with medical errors. When administering pharmaceuticals by means of infusion, dosing errors can occur due to flow rate variability. These dosing errors may lead to adverse effects. We aimed to systematically review the available biomedical literature for in vitro measurement and modeling studies that investigated the physical causes of flow rate variability. Special focus was given to syringe pump setups, which are typically used if very accurate drug delivery is required. We aimed to extract from literature the component with the highest mechanical compliance in syringe pump setups. We included 53 studies, six of which were theoretical models, two articles were earlier reviews of infusion literature, and 45 were in vitro measurement studies. Mechanical compliance, flow resistance, and dead volume of infusion systems were stated as the most important and frequently identified physical causes of flow rate variability. The syringe was indicated as the most important source of mechanical compliance in syringe pump setups (9.0*10-9 to 2.1*10-8 l/Pa). Mechanical compliance caused longer flow rate start-up times (from several minutes up to approximately 70 min) and delayed occlusion alarm times (up to 117 min). PMID- 26352349 TI - Primary standards for measuring flow rates from 100 nl/min to 1 ml/min - gravimetric principle. AB - Microflow and nanoflow rate calibrations are important in several applications such as liquid chromatography, (scaled-down) process technology, and special health-care applications. However, traceability in the microflow and nanoflow range does not go below 16 MUl/min in Europe. Furthermore, the European metrology organization EURAMET did not yet validate this traceability by means of an intercomparison between different National Metrology Institutes (NMIs). The NMIs METAS, Centre Technique des Industries Aerauliques et Thermiques, IPQ, Danish Technological Institute, and VSL have therefore developed and validated primary standards to cover the flow rate range from 0.1 MUl/min to at least 1 ml/min. In this article, we describe the different designs and methods of the primary standards of the gravimetric principle and the results obtained at the intercomparison for the upper flow rate range for the various NMIs and Bronkhorst High-Tech, the manufacturer of the transfer standards used. PMID- 26352350 TI - Primary standard for liquid flow rates between 30 and 1500 nl/min based on volume expansion. AB - An increasing number of microfluidic systems operate at flow rates below 1 MUl/min. Applications include (implanted) micropumps for drug delivery, liquid chromatography, and microreactors. For the applications where the absolute accuracy is important, a proper calibration is required. However, with standard calibration facilities, flow rate calibrations below ~1 MUl/min are not feasible because of a too large calibration uncertainty. In the current research, a traceable flow rate using a certain temperature increase rate is proposed. When the fluid properties, starting mass, and temperature increase rate are known, this principle yields a direct link to SI units, which makes it a primary standard. In this article, it will be shown that this principle enables flow rate uncertainties in the order of 2-3% for flow rates from 30 to 1500 nl/min. PMID- 26352351 TI - An adjustable flow restrictor for implantable infusion pumps based on porous ceramics. AB - This paper describes an adjustable flow restrictor for use in gas-driven implantable infusion pumps, which is based on the resistance of a flow through a porous ceramic material. The flow inside the walls of a ceramic tube can be adjusted between 270 nl/min and 1260 nl/min by changing the flow path length in the ceramic over a distance of 14 mm. The long-term stability of the flow restrictor has been analyzed. A drift of -8% from the nominal value was observed, which lies within the required tolerance of +/-10% after 30 days. The average time needed to change the flow rate is 40 s. In addition, the maximum adjustment time was 110 s, which also lies within the specification. PMID- 26352352 TI - In vitro comparison of two changeover methods for vasoactive drug infusion pumps: quick-change versus automated relay. AB - This study aimed to compare in vitro two syringe changeover techniques to determine which was better at minimising variations in norepinephrine (NE) delivery: the manual quick-change or automated technique. NE concentration was measured continuously using a UV spectrophotometer, and infusion flow rate was monitored by an infusion pump tester. Syringe changeovers were made with either of the two techniques studied. Relays induced disturbances in drug delivery. The temporary increase in NE mass flow rate was significantly higher with manual relays than with automated ones. The automated relay offered a better control of the amounts of NE administered than the quick-change technique. PMID- 26352353 TI - How to use current practice, risk analysis and standards to define hospital-wide policies on the safe use of infusion technology. AB - Infusion therapy is widely used in hospitals. It is well known that medication errors constitute one of the highest risks to patient safety, leading to numerous adverse events concerning incorrect application of infusion technology. Both clinical practice and in vitro studies show that infusion of multiple medications via one access point induces unwanted phenomena such as backflow and an incorrect system response to interventions. Within the Metrology for Drug Delivery project, we addressed the role of infusion devices in drug delivery. We surveyed current practices for application in hospitals to provide input to standards and quality norms for the materials used in infusion technology. Furthermore, we organized meetings with clinicians and other relevant stakeholders to set up a risk analysis-based infusion policy, accompanied by easy to access operating procedures on infusion technology. It was found difficult to establish clear-cut infusion safety guidelines based on quantitative data because of the many different application areas and stakeholders. However, both the expert team and the survey indicated the value of multidisciplinary qualitative discussion for defining best practices. We advise to incorporate specific requirements on infusion devices in protocols and standards, adjusted to specific applications, to ensure safe use of infusion technology. PMID- 26352354 TI - Capillary electrophoresis based on nucleic acid detection for diagnosing human infectious disease. AB - Rapid transmission, high morbidity, and mortality are the features of human infectious diseases caused by microorganisms, such as bacteria, fungi, and viruses. These diseases may lead within a short period of time to great personal and property losses, especially in regions where sanitation is poor. Thus, rapid diagnoses are vital for the prevention and therapeutic intervention of human infectious diseases. Several conventional methods are often used to diagnose infectious diseases, e.g. methods based on cultures or morphology, or biochemical tests based on metabonomics. Although traditional methods are considered gold standards and are used most frequently, they are laborious, time consuming, and tedious and cannot meet the demand for rapid diagnoses. Disease diagnosis using capillary electrophoresis methods has the advantages of high efficiency, high throughput, and high speed, and coupled with the different nucleic acid detection strategies overcomes the drawbacks of traditional identification methods, precluding many types of false positive and negative results. Therefore, this review focuses on the application of capillary electrophoresis based on nucleic detection to the diagnosis of human infectious diseases, and offers an introduction to the limitations, advantages, and future developments of this approach. PMID- 26352355 TI - Possible role of fructosamine 3-kinase genotyping for the management of diabetic patients. AB - Diabetes mellitus is a global pandemic and continues to increase in numbers and significance. Several pathogenic processes are involved in the development of such disease and these mechanisms could be influenced by genetic, epigenetic and environmental factors. Non-enzymatic glycation reactions of proteins have been strongly related to pathogenesis of chronic diabetic complications. The identification of fructosamine 3-kinase (FN3K), an enzyme involved in protein deglycation, a new form of protein repair, is of great interest. FN3K phosphorylates fructosamines on the third carbon of their sugar moiety, making them unstable and causing them to detach from proteins, suggesting a protective role of this enzyme. Moreover, the variability in FN3K activity has been associated with some polymorphisms in the FN3K gene. Here we argue about genetic studies and evidence of FN3K involvement in diabetes, together with results of our analysis of the FN3K gene on a Caucasian cohort of diabetic patients. Present knowledge suggests that FN3K could act in concert with other molecular mechanisms and may impact on gene expression and activity of other enzymes involved in deglycation process. PMID- 26352356 TI - Sequence-specific DNA nicking endonucleases. AB - A group of small HNH nicking endonucleases (NEases) was discovered recently from phage or prophage genomes that nick double-stranded DNA sites ranging from 3 to 5 bp in the presence of Mg2+ or Mn2+. The cosN site of phage HK97 contains a gp74 nicking site AC?CGC, which is similar to AC?CGR (R=A/G) of N.phiGamma encoded by Bacillus phage Gamma. A minimal nicking domain of 76 amino acid residues from N.phiGamma could be fused to other DNA binding partners to generate chimeric NEases with new specificities. The biological roles of a few small HNH endonucleases (HNHE, gp74 of HK97, gp37 of phiSLT, phi12 HNHE) have been demonstrated in phage and pathogenicity island DNA packaging. Another group of NEases with 3- to 7-bp specificities are either natural components of restriction systems or engineered from type IIS restriction endonucleases. A phage group I intron-encoded HNH homing endonucleases, I-PfoP3I was found to nick DNA sites of 14-16 bp. I-TslI encoded by T7-like PhiI appeared to nick DNA sites with a 9-bp core sequence. DNA nicking and labeling have been applied to optical mapping to aid genome sequence assembly and detection of large insertion/deletion mutations in genomic DNA of cancer cells. Nicking enzyme-mediated amplification reaction has been applied to rapid diagnostic testing of influenza A and B in clinical setting and for construction of DNA-based Boolean logic gates. The clustered regularly interspaced short palindromic repeats-ribonucleoprotein complex consisting of engineered Cas9 nickases in conjunction with tracerRNA:crRNA or a single-guide RNA have been successfully used in genome modifications. PMID- 26352357 TI - The redox switch that regulates molecular chaperones. AB - Modification of reactive cysteine residues plays an integral role in redox regulated reactions. Oxidation of thiolate anions to sulphenic acid can result in disulphide bond formation, or overoxidation to sulphonic acid, representing reversible and irreversible endpoints of cysteine oxidation, respectively. The antioxidant systems of the cell, including the thioredoxin and glutaredoxin systems, aim to prevent these higher and irreversible oxidation states. This is important as these redox transitions have numerous roles in regulating the structure/function relationship of proteins. Proteins with redox-active switches as described for peroxiredoxin (Prx) and protein disulphide isomerase (PDI) can undergo dynamic structural rearrangement resulting in a gain of function. For Prx, transition from cysteine sulphenic acid to sulphinic acid is described as an adaptive response during increased cellular stress causing Prx to form higher molecular weight aggregates, switching its role from antioxidant to molecular chaperone. Evidence in support of PDI as a redox-regulated chaperone is also gaining impetus, where oxidation of the redox-active CXXC regions causes a structural change, exposing its hydrophobic region, facilitating polypeptide folding. In this review, we will focus on these two chaperones that are directly regulated through thiol-disulphide exchange and detail how these redox-induced switches allow for dual activity. Moreover, we will introduce a new role for a metabolic protein, the branched-chain aminotransferase, and discuss how it shares common mechanistic features with these well-documented chaperones. Together, the physiological importance of the redox regulation of these proteins under pathological conditions such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis will be discussed to illustrate the impact and importance of correct folding and chaperone-mediated activity. PMID- 26352358 TI - Pupylation-dependent and -independent proteasomal degradation in mycobacteria. AB - Bacteria make use of compartmentalizing protease complexes, similar in architecture but not homologous to the eukaryotic proteasome, for the selective and processive removal of proteins. Mycobacteria as members of the actinobacteria harbor proteasomes in addition to the canonical bacterial degradation complexes. Mycobacterial proteasomal degradation, although not essential during normal growth, becomes critical for survival under particular environmental conditions, like, for example, during persistence of the pathogenic Mycobacterium tuberculosis in host macrophages or of environmental mycobacteria under starvation. Recruitment of protein substrates for proteasomal degradation is usually mediated by pupylation, the post-translational modification of lysine side chains with the prokaryotic ubiquitin-like protein Pup. This substrate recruitment strategy is functionally reminiscent of ubiquitination in eukaryotes, but is the result of convergent evolution, relying on chemically and structurally distinct enzymes. Pupylated substrates are recognized by the ATP-dependent proteasomal regulator Mpa that associates with the 20S proteasome core. A pupylation-independent proteasome degradation pathway has recently been discovered that is mediated by the ATP-independent bacterial proteasome activator Bpa (also referred to as PafE), and that appears to play a role under stress conditions. In this review, mechanistic principles of bacterial proteasomal degradation are discussed and compared with functionally related elements of the eukaryotic ubiquitin-proteasome system. Special attention is given to an understanding on the molecular level based on structural and biochemical analysis. Wherever available, discussion of in vivo studies is included to highlight the biological significance of this unusual bacterial degradation pathway. PMID- 26352361 TI - Upper and Lower Eyelid Full Thickness Reconstruction Using a Retrograde Postauricular Island Flap. AB - Upper and lower eyelid full-thickness reconstruction in a patient without available adjacent tissue because of burns or trauma is a surgical challenge. Our patient had severe thermal burns with complete unilateral defects in both the upper and lower eyelids. Although the skin grafts survived, contraction occurred quickly, subsequent ectropion of both the upper and lower eyelids, which could have lead to exposure keratitis and blurred vision. A retrograde postauricular island flap was harvested to provide skin eyelid coverage, and the donor site was directly closed. After another 2 surgeries, normal skin thickness and a color matched appearance were achieved, and the donor-site scar was almost invisible from the anterior view. To our knowledge, it is rare to use a retrograde postauricular island flap in a full-thickness reconstruction of both the upper and lower eyelids, but the authors have ascertained that this method may be a reliable option in such selected and challenging situations. PMID- 26352362 TI - Suture Autotransplantation and Dural Stripping for Craniosynostosis: A Long-Term Growth Study in Humans. AB - OBJECTIVE: Craniosynostosis treatment by suture autotransplantation and dura stripping has proven to be successful in animals. When applied clinically, it may reduce operative morbidity and postoperative growth disturbances known to occur after radical remodeling. It may prevent resynostosis, which is known to occur after simple synostostectomy. It may prevent subcutaneous fluid collections known to occur after synostectomy and dura stripping. STUDY DESIGN: Four synostostic infants have been treated using this concept and followed up by computerized scans. The distance between markers on each side of the transplanted sutures (6 in total) has been monitored from 1.5 to 7 years. RESULTS: The transplanted suture areas remained intact, and the sutures remained patent and experienced growth. A fifth patient with similar results was published earlier as a case report. CONCLUSIONS: Suture transplantation and dural stripping should be further studied in future multicenter studies with larger series, comprising syndromic and nonsyndromic synostosis patients. PMID- 26352363 TI - Is Off-Axis Tilted Implant a Better Option Than Maxillary Sinus Lift Procedure in Posterior Edentulous Maxilla-A Comparative Study. PMID- 26352364 TI - Volume Measurement of Various Tissues Using the Image J Software. AB - Various methods have been introduced to assess the tissue volume because volumetric evaluation is recognized as one of the most important steps in reconstructive surgery. Advanced volume measurement methods proposed recently use three-dimensional images. They are convenient but have drawbacks such as requiring expensive equipment and volume-analysis software. The authors devised a volume measurement method using the Image J software, which is in the public domain and does not require specific devices or software packages. The orbital and breast volumes were measured by our method using Image J data from facial computed tomography (CT) and breast magnetic resonance imaging (MRI). The authors obtained the final volume results, which were similar to the known volume values. The authors propose here a cost-effective, simple, and easily accessible volume measurement method using the Image J software. PMID- 26352365 TI - Surgical Intervention for Masticatory Muscle Tendon-Aponeurosis Hyperplasia Based on the Diagnosis Using the Four-Dimensional Muscle Model. AB - OBJECTIVES: The surgical target of Masticatory muscle tendon-aponeurosis hyperplasia (MMTAH) is the masseter or temporal muscle. In our clinic, the 4 dimentional muscle model (4DMM) has been used to decide if we should approach to the masseter or temporal muscle. The aim of this study is validate the clinical usefulness of 4DMM on the basis of the surgical results. METHODS: The 4DMM was constructed from the digital data of 3D-CT and 4-dimentional mandibular movements of the patients. It made us to able to visually observe the expansion rate of masticatory muscles at maximum mouth opening comparing to their length at closed mouth position. Fifteen patients were applied the 4DMM before the surgical treatment and 2 healthy volunteers were enrolled as control group. RESULTS: The expansion rate of temporal muscle at the maximum mouth opening in the patient group was significantly less than that in the control group (P < 0.05). On the other hand, the masseter muscles of all patients were expanded as same as the control group. Therefore the main cause of limitation of mouth-opening was suggested to be a contracture of the temporal muscle. Consequently, we performed successful bilateral coronoidectomy with no surgical intervention to the masseter muscles in all patients. CONCLUSION: The present 4DMM would be valuable modality to decide the target muscle of surgical treatment for patients with MMTAH. In this pathology, contracture of the temporal muscle seems to be main cause of limited mouth opening. PMID- 26352366 TI - Endonasal Endoscopic Transsphenoidal Approach to Lesions of the Sellar Region in Pediatric Patients. AB - OBJECTIVE: Endoscopic endonasal (transnasal) transsphenoidal approach (EETA) for management of sellar lesions has gained popularity as a reliable and atraumatic method. Most reported studies of EETA have focused on surgical outcome in adult patients; and there are few reports to describe outcome in pediatric patients. The authors report our early experience of 11 patients aged 14 to 18 years managed with EETA to evaluate the safety and effectiveness of EETA in the pediatric. METHODS: Retrospective review of hospital records of 11 pediatric patients who underwent endonasal endoscopic transsphenoidal approach for resection of sellar region lesion over 2 years. Age, sex, symptoms, tumor size, extent of tumor resection, clinical outcome, and surgical complications were reviewed. RESULTS: Total resection was achieved in 9 (81.8%) patients, subtotal resection in 2 (18.2%), and no patient had partial or insufficient resection. All (100%) patients achieved visual remission, 7 (87.5%) of 8 patients with hyperhormone preoperative had endocrinological remission. Two (18.2%) patients incurred temporary diabetes insipidus (DI) postoperatively. One (9.1%) patient incurred postoperative cerebrospinal fluid (CSF) leakage which resolved following lumbar drainage. Three (27.3%) patients developed hypopituitarism needed hormone replacement therapy. There were no cases of meningitis, intracranial hematoma, or death. CONCLUSIONS: Endoscopic endonasal (transnasal) transsphenoidal approach (EETA) provides a safe and effective surgical option with low morbidity and mortality in pediatric patients. PMID- 26352367 TI - Minimally Invasive Temporal Brow Lift. PMID- 26352368 TI - Diagnosis and Management of Ossified Chronic Subdural Hematoma. PMID- 26352369 TI - Amyotrophic lateral sclerosis: What nurses need to know. PMID- 26352370 TI - New drugs 2015, part 3. PMID- 26352371 TI - The truth, the whole truth, and nothing but the truth... PMID- 26352372 TI - Novel Carbazole-Based Hole-Transporting Materials with Star-Shaped Chemical Structures for Perovskite-Sensitized Solar Cells. AB - Novel carbazole-based hole-transporting materials (HTMs), including extended pi conjugated central core units such as 1,4-phenyl, 4,4'-biphenyl, or 1,3,5 trisphenylbenzene for promoting effective pi-pi stacking as well as the hexyloxy flexible group for enhancing solubility in organic solvent, have been synthesized as HTM of perovskite-sensitized solar cells. A HTM with 1,3,5-trisphenylbenzene core, coded as SGT-411, exhibited the highest charge conductivity caused by its intrinsic property to form crystallized structure. The perovskite-sensitized solar cells with SGT-411 exhibited the highest PCE of 13.00%, which is 94% of that of the device derived from spiro-OMeTAD (13.76%). Time-resolved photoluminescence spectra indicate that SGT-411 shows the shortest decay time constant, which is in agreement with the trends of conductivity data, indicating it having fastest charge regeneration. In this regard, a carbazole-based HTM with star-shaped chemical structure is considered to be a promising candidate HTM. PMID- 26352373 TI - Preoperative Surgical Risk Predictions Are Not Meaningfully Improved by Including the Surgical Apgar Score: An Analysis of the Risk Quantification Index and Present-On-Admission Risk Models. AB - BACKGROUND: Estimating surgical risk is critical for perioperative decision making and risk stratification. Current risk-adjustment measures do not integrate dynamic clinical parameters along with baseline patient characteristics, which may allow a more accurate prediction of surgical risk. The goal of this study was to determine whether the preoperative Risk Quantification Index (RQI) and Present On-Admission Risk (POARisk) models would be improved by including the intraoperative Surgical Apgar Score (SAS). METHODS: The authors identified adult patients admitted after noncardiac surgery. The RQI and POARisk were calculated using published methodologies, and model performance was compared with and without the SAS. Relative quality was measured using Akaike and Bayesian information criteria. Calibration was compared by the Brier score. Discrimination was compared by the area under the receiver operating curves (AUROCs) using a bootstrapping procedure for bias correction. RESULTS: SAS alone was a statistically significant predictor of both 30-day mortality and in-hospital mortality (P < 0.0001). The RQI had excellent discrimination with an AUROC of 0.8433, which increased to 0.8529 with the addition of the SAS. The POARisk had excellent discrimination with an AUROC of 0.8608, which increased to 0.8645 by including the SAS. Similarly, overall performance and relative quality increased. CONCLUSIONS: While AUROC values increased, the RQI and POARisk preoperative risk models were not meaningfully improved by adding intraoperative risk using the SAS. In addition to the estimated blood loss, lowest heart rate, and lowest mean arterial pressure, other dynamic clinical parameters from the patient's intraoperative course may need to be combined with procedural risk estimate models to improve risk stratification. PMID- 26352375 TI - Emergency Cricothyrotomy: Toward a Safer and More Reliable Rescue Method in "Cannot Intubate, Cannot Oxygenate" Situation. PMID- 26352374 TI - Altered Mitochondrial Dynamics Contributes to Propofol-induced Cell Death in Human Stem Cell-derived Neurons. AB - BACKGROUND: Studies in developing animals have shown that anesthetic agents can lead to neuronal cell death and learning disabilities when administered early in life. Development of human embryonic stem cell-derived neurons has provided a valuable tool for understanding the effects of anesthetics on developing human neurons. Unbalanced mitochondrial fusion and fission lead to various pathological conditions including neurodegeneration. The aim of this study was to dissect the role of mitochondrial dynamics in propofol-induced neurotoxicity. METHODS: Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate in situ nick-end labeling staining was used to assess cell death in human embryonic stem cell-derived neurons. Mitochondrial fission was assessed using TOM20 staining and electron microscopy. Expression of mitochondrial fission-related proteins was assessed by Western blot, and confocal microscopy was used to assess opening time of the mitochondrial permeability transition pore (mPTP). RESULTS: Exposure to 6 h of 20 MUg/ml propofol increased cell death from 3.18 +/- 0.17% in the control treated group to 9.6 +/- 0.95% and led to detrimental increases in mitochondrial fission (n = 5 coverslips per group) accompanied by increased expression of activated dynamin-related protein 1 and cyclin-dependent kinase 1, key proteins responsible for mitochondrial fission. Propofol exposure also induced earlier opening of the mPTP from 118.9 +/- 3.1 s in the control-treated group to 73.3 +/- 1.6 s. Pretreatment of the cells with mdivi-1, a mitochondrial fission blocker rescued the propofol-induced toxicity, mitochondrial fission, and mPTP opening time (n = 75 cells per group). Inhibiting cyclin-dependent kinase 1 attenuated the increase in cell death and fission and the increase in expression of activated dynamin-related protein 1. CONCLUSION: These data demonstrate for the first time that propofol-induced neurotoxicity occurs through a mitochondrial fission/mPTP-mediated pathway. PMID- 26352376 TI - Ultrasound Improves Cricothyrotomy Success in Cadavers with Poorly Defined Neck Anatomy: A Randomized Control Trial. AB - BACKGROUND: Misidentification of the cricothyroid membrane in a "cannot intubate cannot oxygenate" situation can lead to failures and serious complications. The authors hypothesized that preprocedure ultrasound-guided identification of the cricothyroid membrane would reduce complications associated with cricothyrotomy. METHODS: A group of 47 trainees were randomized to digital palpation (n = 23) and ultrasound (n = 24) groups. Cricothyrotomy was performed on human cadavers by using the Portex device (Smiths Medical, USA). Anatomical landmarks of cadavers were graded as follows: grade 1-easy = visual landmarks; 2-moderate = requires light palpation of landmarks; 3-difficult = requires deep palpation of landmarks; and 4-impossible = landmarks not palpable. Primary outcome was the complication rate as measured by the severity of injuries. Secondary outcomes were correct device placement, failure to cannulate, and insertion time. RESULTS: Ultrasound guidance significantly decreased the incidence of injuries to the larynx and trachea (digital palpation: 17 of 23 = 74% vs. ultrasound: 6 of 24 = 25%; relative risk, 2.88; 95% CI, 1.39 to 5.94; P = 0.001) and increased the probability of correct insertion by 5.6 times (P = 0.043) in cadavers with difficult and impossible landmark palpation (digital palpation 8.3% vs. ultrasound 46.7%). Injuries were found in 100% of the grades 3 to 4 (difficult impossible landmark palpation) cadavers by digital palpation compared with only 33% by ultrasound (P < 0.001). The mean (SD) insertion time was significantly longer with ultrasound than with digital palpation (196.1 s [60.6 s] vs. 110.5 s [46.9 s]; P < 0.001). CONCLUSION: Preprocedure ultrasound guidance in cadavers with poorly defined neck anatomy significantly reduces complications and improves correct insertion of the airway device in the cricothyroid membrane. PMID- 26352377 TI - Gradually Increased Oxygen Administration Improved Oxygenation and Mitigated Oxidative Stress after Resuscitation from Severe Hemorrhagic Shock. AB - BACKGROUND: The optimal oxygen administration strategy during resuscitation from hemorrhagic shock (HS) is still controversial. Improving oxygenation and mitigating oxidative stress simultaneously seem to be contradictory goals. To maximize oxygen delivery while minimizing oxidative damage, the authors proposed the notion of gradually increased oxygen administration (GIOA), which entails making the arterial blood hypoxemic early in resuscitation and subsequently gradually increasing to hyperoxic, and compared its effects with normoxic resuscitation, hyperoxic resuscitation, and hypoxemic resuscitation in severe HS. METHODS: Rats were subjected to HS, and on resuscitation, the rats were randomly assigned to four groups (n = 8): the normoxic, the hyperoxic, the hypoxemic, and the GIOA groups. Rats were observed for an additional 1 h. Hemodynamics, acid base status, oxygenation, and oxidative injury were observed and evaluated. RESULTS: Central venous oxygen saturation promptly recovered only in the hyperoxic and the GIOA groups, and the liver tissue partial pressure of oxygen was highest in the GIOA group after resuscitation. Oxidative stress in GIOA group was significantly reduced compared with the hyperoxic group as indicated by the reduced malondialdehyde content, increased catalase activity, and the lower histologic injury scores in the liver. In addition, the tumor necrosis factor alpha and interleukin-6 expressions in the liver were markedly decreased in the GIOA group than in the hyperoxic and normoxic groups as shown by the immunohistochemical staining. CONCLUSIONS: GIOA improved systemic/tissue oxygenation and mitigated oxidative stress simultaneously after resuscitation from severe HS. GIOA may be a promising strategy to improve resuscitation from HS and deserves further investigation. PMID- 26352378 TI - Spinal IL-33/ST2 Signaling Contributes to Neuropathic Pain via Neuronal CaMKII CREB and Astroglial JAK2-STAT3 Cascades in Mice. AB - BACKGROUND: Emerging evidence indicates that nerve damage-initiated neuroinflammation and immune responses, which are evidenced by the up-regulation of proinflammatory cytokines, contribute to the development of neuropathic pain. This study investigated the role of spinal interleukin (IL)-33 and its receptor ST2 in spared nerve injury (SNI)-induced neuropathic pain. METHODS: The von Frey test and acetone test were performed to evaluate neuropathic pain behaviors (n = 8 to 12), and Western blot (n = 4 to 6), immunohistochemistry, real-time polymerase chain reaction (n = 5), and Bio-Plex (n = 5) assays were performed to understand the molecular mechanisms. RESULTS: Intrathecal administration of ST2 neutralizing antibody or ST2 gene knockout (ST2) significantly attenuated the SNI induced mechanical and cold allodynia. On the 7th day after SNI, the expression of spinal IL-33 and ST2 was increased by 255.8 +/- 27.3% and 266.4 +/- 83.5% (mean +/- SD), respectively. Mechanistic studies showed that the increased expression of the spinal N-methyl-D-aspartate (NMDA) receptor subunit 1 after SNI was reduced by ST2 antibody administration or ST2. The induction of nociceptive behaviors in naive mice due to recombinant IL-33 was reversed by the noncompetitive NMDA antagonist MK-801. ST2 antibody administration or ST2 markedly inhibited the increased activation of the astroglial janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) cascade and the neuronal calcium-calmodulin-dependent kinase II (CaMKII)-cyclic adenosine monophosphate response element-binding protein (CREB) cascade after SNI. Moreover, intrathecal pretreatment with the CaMKII inhibitor KN-93 or the JAK2 STAT3 cascade inhibitor AG490 attenuated recombinant IL-33-induced nociceptive behaviors and NMDA subunit 1 up-regulation in naive mice. CONCLUSION: Spinal IL 33/ST2 signaling contributes to neuropathic pain by activating the astroglial JAK2-STAT3 cascade and the neuronal CaMKII-CREB cascade. PMID- 26352379 TI - Reliability of Reliability Adjustment for Quality Improvement and Value-based Payment. PMID- 26352380 TI - Initial Experience of an Anesthesiology-based Service for Perioperative Management of Pacemakers and Implantable Cardioverter Defibrillators. AB - BACKGROUND: Management of cardiovascular implantable electronic devices (CIEDs), including pacemakers and implantable cardioverter defibrillators, for surgical procedures is challenging due to the increasing number of patients with CIEDs and limited availability of trained providers. At the authors' institution, a small group of anesthesiologists were trained to interrogate CIEDs, devise a management plan, and perform preoperative and postoperative programming and device testing whenever necessary. METHODS: Patients undergoing surgery between October 1, 2009 and June 30, 2013 at the University of Washington Medical Center were included in a retrospective chart review to determine the number of devices actively managed by the Electrophysiology/Cardiology Service (EPCS) versus the Anesthesiology Device Service (ADS), changes in workload over time, surgical case delays due to device management, and errors and problems encountered in device programming. RESULTS: The EPCS managed 254 CIEDs, the ADS managed 548, and 227 by neither service. Over time, the ADS providers managed an increasing percentage of devices with decreasing supervision from the EPCS. Only two CIEDs managed by the ADS required immediate assistance from the EPCS. Patients who were unstable postoperatively were referred to the EPCS. Although numerous issues in programming were encountered, primarily when restoring demand pacing after programming asynchronous pacing for surgery, no patient harm resulted from ADS or EPCS management of CIEDs. CONCLUSIONS: An ADS can provide safe CIED management for surgery, but it requires specialized provider training and strong support from the EPCS. Due to the complexity of CIED management, an ADS will likely only be feasible in high-volume settings. PMID- 26352381 TI - Identification and Characterization of GAL-021 as a Novel Breathing Control Modulator. AB - BACKGROUND: The authors describe the preclinical pharmacological properties of GAL-021, a novel peripheral chemoreceptor modulator. METHODS: The ventilatory effects of GAL-021 were characterized using tracheal pneumotachometry (n = 4 to 6), plethysmography (n = 5 to 6), arterial blood gas analyses (n = 6 to 11), and nasal capnography (n = 3 to 4) in naive animals and those subjected to morphine induced respiratory depression. Morphine analgesia in rats was evaluated by tail flick test (n = 6). Carotid body involvement in GAL-021 ventilatory effects was assessed by comparing responses in intact and carotid sinus nerve-transected rats. Hemodynamic effects of GAL-021 were evaluated in urethane-anesthetized rats (n = 7). The pharmacological profile of GAL-021 in vitro was investigated using radioligand binding, enzyme inhibition, and cellular electrophysiology assays. RESULTS: GAL-021 given intravenously stimulated ventilation and/or attenuated opiate-induced respiratory depression in rats, mice, and nonhuman primates, without decreasing morphine analgesia in rats. GAL-021 did not alter mean arterial pressure but produced a modest increase in heart rate. Ventilatory stimulation in rats was attenuated by carotid sinus nerve transection. GAL-021 inhibited KCa1.1 in GH3 cells, and the evoked ventilatory stimulation was attenuated in Slo1 mice lacking the pore-forming alpha-subunit of the KCa1.1 channel. CONCLUSIONS: GAL-021 behaved as a breathing control modulator in rodents and nonhuman primates and diminished opioid-induced respiratory depression without compromising opioid analgesia. It acted predominantly at the carotid body, in part by inhibiting KCa1.1 channels. Its preclinical profile qualified the compound to enter clinical trials to assess effects on breathing control disorders such as drug (opioid)-induced respiratory depression and sleep apnea. PMID- 26352382 TI - Stemming the Tide of Obstetric Morbidity: An Opportunity for the Anesthesiologist to Embrace the Role of Peridelivery Physician. PMID- 26352384 TI - Hyperthermia induces apoptosis by targeting Survivin in esophageal cancer. AB - Hyperthermia is considered the fifth pillar of cancer treatment. It induces cancer cell apoptosis, however, its molecular mechanisms remain unclear. In the present study, the role of Survivin in hyperthermia-induced apoptosis in esophageal cancer was investigated. Different temperatures were used to treat EC109 esophageal cancer cells, and their viability was found to be significantly inhibited with a concomitant increase in apoptosis and necrosis. Necrosis increased in a temperature-dependent manner, whereas peak apoptosis was reached at 43C. The hyperthermia-induced apoptosis was due to the inhibition of Survivin and the activation of caspase-3. Subsequently, overexpression of Survivin inhibited the activation of caspase-3 and hyperthermia-induced apoptosis, however, this inhibition was reversed in the absence of XIAP. Immunoprecipitations showed that Survivin did not directly bind to caspase-3, whereas XIAP interacted with Survivin and caspase-3. Immunohistochemistry was performed to detect the expression of Survivin in esophageal cancer patient samples. A higher expression of Survivin in esophageal cancer tissues compared to normal tissues was observed, and a high expression correlated with poor prognosis. The results indicated that hyperthermia decreases the expression of Survivin, prevents its binding to XIAP, activates caspase-3 and induces apoptosis. Due to its correlation with poor prognosis, Survivin may be a target for hyperthermia in the treatment of esophageal cancer. PMID- 26352383 TI - Expression of leukemia inhibitory factor in the rat retina following acute ocular hypertension. AB - The aim of the present study was to investigate the expression of leukemia inhibitory factor (LIF) and its downstream signaling pathways in the rat retina following acute ocular hypertension. The intraocular pressure of the rats was elevated to 110 mmHg for 1 h by infusing the anterior chamber with normal saline. The retinal tissues were obtained 12 h, 24 h, and 2, 3 and 7 days after termination of the ocular hypertension. Hematoxylin and eosin and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were performed to assess the morphological changes and the apoptosis of retinal cells, respectively. Quantification of the retinal ganglion cells (RGCs) was performed using fluorogold retrograde (FG) staining. The expression levels of LIF, LIF receptor (LIFR), signal transducers and activators of transcription 3 (STAT3), phosphorylated STAT3 (P-STAT3), Akt, phosphorylated-Akt (P-Akt), extracellular signal-regulated kinase (ERK) and phosphorylated ERK (P-ERK) were determined at different time-points following acute ocular hypertension using western blot analysis. Reverse transcription-quantitative polymerase chain reaction was performned to detect the mRNA expression levels of LIF and LIFR. The results revealed that 12 h, 24 h, 2, 3 and 7 days after reperfusion, the thickness of the inner nuclear layer and the inner plexiform layer was decreased, with a significant reduction in the number of RGCs, as determined using TUNEL and FG staining. The expression levels of LIF and LIFR were increased following acute ocular hypertension. At 12 h post-retinal reperfusion, the expression levels of P STAT3 and P-Akt were significantly upregulated, while the expression of P-ERK was decreased. The changes in the expression levels of LIF and LIFR suggested that LIF may be important in the process of degeneration/protection following retinal ischemia induced by acute ocular hypertension, via activation of the Janus kinase/STAT and Akt signaling pathways. PMID- 26352386 TI - The Long-Term Outcome of the Turner-Warwick Vaginal Obturator Shelf Urethral Repositioning Colposuspension Procedure for Urodynamically Proven Stress Urinary Incontinence. AB - OBJECTIVE: To analyze long-term continence, voiding dysfunction and secondary prolapse rates following Turner-Warwick Vaginal Obturator Shelf Urethral Repositioning colposuspension (VOSURP) for urodynamically proven stress urinary incontinence (USUI). PATIENTS AND METHODS: Telephone and/or outpatient review of the outcomes of 50 consecutive patients undergoing VOSURP between 1997 and 2008 was conducted. Outcomes assessed included urinary continence (pad free/leak free), need to self-catheterise (ISC), secondary posterior pelvic organ prolapse (POP) development and need for further continence and POP-related surgical interventions. All patients with continued/recurrent urinary incontinence had repeat videourodynamics. RESULTS: At a median follow-up of 108.5 months (17-153), complete urinary continence was reported in 41 (82%) of patients, post procedure new onset ISC in 2 (4%) and new onset posterior POP in 2 (4%). The cause of continued urinary incontinence was persistent USUI in 3 (6%), new onset idiopathic detrusor overactivity (IDO) in 4 (8%) and failure of resolution of pre existing IDO in 2 (4%). CONCLUSIONS: Long-term complete urinary continence and cure of USUI following VOSURP are excellent at 82 and 94%, respectively. Voiding dysfunction and secondary POP procedure rates are low. The VOSURP is an excellent alternative to classical Burch colposuspension for the treatment of primary and recurrent USUI. PMID- 26352385 TI - From Theory to Practice: Implementation of a Resource Allocation Model in Health Departments. AB - OBJECTIVE: To develop a resource allocation model to optimize health departments' Centers for Disease Control and Prevention (CDC)-funded HIV prevention budgets to prevent the most new cases of HIV infection and to evaluate the model's implementation in 4 health departments. DESIGN, SETTINGS, AND PARTICIPANTS: We developed a linear programming model combined with a Bernoulli process model that allocated a fixed budget among HIV prevention interventions and risk subpopulations to maximize the number of new infections prevented. The model, which required epidemiologic, behavioral, budgetary, and programmatic data, was implemented in health departments in Philadelphia, Chicago, Alabama, and Nebraska. MAIN OUTCOME MEASURES: The optimal allocation of funds, the site specific cost per case of HIV infection prevented rankings by intervention, and the expected number of HIV cases prevented. RESULTS: The model suggested allocating funds to HIV testing and continuum-of-care interventions in all 4 health departments. The most cost-effective intervention for all sites was HIV testing in nonclinical settings for men who have sex with men, and the least cost effective interventions were behavioral interventions for HIV-negative persons. The pilot sites required 3 to 4 months of technical assistance to develop data inputs and generate and interpret the results. Although the sites found the model easy to use in providing quantitative evidence for allocating HIV prevention resources, they criticized the exclusion of structural interventions and the use of the model to allocate only CDC funds. CONCLUSIONS: Resource allocation models have the potential to improve the allocation of limited HIV prevention resources and can be used as a decision-making guide for state and local health departments. Using such models may require substantial staff time and technical assistance. These model results emphasize the allocation of CDC funds toward testing and continuum-of-care interventions and populations at highest risk of HIV transmission. PMID- 26352387 TI - Reliable assessment of forearm photoageing by high-frequency ultrasound: a cross sectional study. AB - OBJECTIVE: High-frequency ultrasound is a non-invasive tool used in skin ageing research to assess dermis thickness and echogenicity. This study evaluated the reliability of a range of high-frequency ultrasound parameters and tested their correlation with age and a validated clinical scale for the assessment of forearm skin photoageing; the difference between two body sites according to environmental exposition patterns was also investigated. METHODS: Twenty-three volunteers aged 28-82 years were divided into three groups according to forearm photoageing degree. A 20 MHz ultrasound unit was used to obtain cross-sectional images of the skin by two trained investigators on two different sites: the dorsal forearm (chronically photoexposed skin) and the proximal medial arm (non photoexposed skin). Several echogenicity parameters were studied for each skin compartment: total dermis, upper dermis and lower dermis, and the ratio between upper and lower dermis. RESULTS: The intraclass correlation coefficient (for complete agreement) between investigators was higher for upper and total dermis echogenicity measures compared with the lower dermis. At the non-photoexposed site, the upper and lower dermis parameter ratio was better correlated with age. At the photoexposed area, total dermis parameters demonstrated higher correlations with clinical score. CONCLUSION: The authors discuss the choice of parameters for forearm photoageing assessment using high-frequency ultrasound. PMID- 26352388 TI - The influence of a six-week, high-intensity games intervention on the pulmonary oxygen uptake kinetics in prepubertal obese and normal-weight children. AB - The pulmonary oxygen uptake response is deleteriously influenced by obesity in prepubertal children, as evidenced by a slower phase II response. To date, no studies have investigated the ability of an exercise intervention to ameliorate this. The objective of the study was to investigate the influence of a 6-week, high-intensity, games-orientated intervention on the oxygen uptake kinetic response of prepubertal obese and normal-weight children during heavy-intensity exercise. Thirteen normal-weight and 15 obese children participated in a twice weekly exercise intervention involving repeated bouts of 6-min high-intensity, games-orientated exercises followed by 2 min of recovery. Sixteen normal-weight and 11 obese children served as a control group. At baseline and post intervention, each participant completed a graded-exercise test to volitional exhaustion and constant work-rate, heavy-intensity exercise. Post-intervention, obese children demonstrated a reduced phase II tau (pre-intervention: 30 +/- 8 cf. post-intervention: 24 +/- 7 s), mean response time (pre-intervention: 50 +/- 10 cf. post-intervention: 38 +/- 9 s) and phase II amplitude (pre-intervention: 1.51 +/- 0.30 cf. post-intervention: 1.34 +/- 0.27 L.min(-1)). No changes were evident in the normal-weight children. In conclusion, the present findings demonstrate that a 6-week, high-intensity intervention can have a significant positive impact on the dynamic oxygen uptake response of obese prepubertal children. PMID- 26352389 TI - Utility of different massive parallel sequencing platforms for mutation profiling in clinical samples and identification of pitfalls using FFPE tissue. AB - In the growing field of personalised medicine, the analysis of numerous potential targets is becoming a challenge in terms of work load, tissue availability, as well as costs. The molecular analysis of non-small cell lung cancer (NSCLC) has shifted from the analysis of the epidermal growth factor receptor (EGFR) mutation status to the analysis of different gene regions, including resistance mutations or translocations. Massive parallel sequencing (MPS) allows rapid comprehensive mutation testing in routine molecular pathological diagnostics even on small formalin-fixed, paraffin-embedded (FFPE) biopsies. In this study, we compared and evaluated currently used MPS platforms for their application in routine pathological diagnostics. We initiated a first round-robin testing of 30 cases diagnosed with NSCLC and a known EGFR gene mutation status. In this study, three pathology institutes from Germany received FFPE tumour sections that had been individually processed. Fragment libraries were prepared by targeted multiplex PCR using institution-specific gene panels. Sequencing was carried out using three MPS systems: MiSeqTM, GS Junior and PGM Ion TorrentTM. In two institutes, data analysis was performed with the platform-specific software and the Integrative Genomics Viewer. In one institute, data analysis was carried out using an in-house software system. Of 30 samples, 26 were analysed by all institutes. Concerning the EGFR mutation status, concordance was found in 26 out of 26 samples. The analysis of a few samples failed due to poor DNA quality in alternating institutes. We found 100% concordance when comparing the results of the EGFR mutation status. A total of 38 additional mutations were identified in the 26 samples. In two samples, minor variants were found which could not be confirmed by qPCR. Other characteristic variants were identified as fixation artefacts by reanalyzing the respective sample by Sanger sequencing. Overall, the results of this study demonstrated good concordance in the detection of mutations using different MPS platforms. The failure with samples can be traced back to different DNA extraction systems and DNA quality. Unknown or ambiguous variations (transitions) need verification with another method, such as qPCR or Sanger sequencing. PMID- 26352390 TI - HIV treatment cascade in tuberculosis patients. AB - PURPOSE OF REVIEW: Globally, the number of deaths associated with tuberculosis (TB) and HIV coinfection remains unacceptably high. We review the evidence around the impact of strengthening the HIV treatment cascade in TB patients and explore recent findings about how best to deliver integrated TB/HIV services. RECENT FINDINGS: There is clear evidence that the timely provision of antiretroviral therapy (ART) reduces mortality in TB/HIV coinfected adults. Despite this, globally in 2013, only around a third of known HIV-positive TB cases were treated with ART. Although there is some recent evidence exploring the barriers to achieve high coverage of HIV testing and ART initiation in TB patients, our understanding of which factors are most important and how best to address these within different health systems remains incomplete. There are some examples of good practice in the delivery of integrated TB/HIV services to improve the HIV treatment cascade. However, evidence of the impact of such strategies is of relatively low quality for informing integrated TB/HIV programming more broadly. In most settings, there remain barriers to higher-level organizational and functional integration. SUMMARY: There remains a need for commitment to patient centred integrated TB/HIV care in countries affected by the dual epidemic. There is a need for better quality evidence around how best to deliver integrated services to strengthen the HIV treatment cascade in TB patients, both at primary healthcare level and within community settings. PMID- 26352391 TI - Mother and child both matter: reconceptualizing the prevention of mother-to-child transmission care continuum. AB - PURPOSE OF REVIEW: To propose a prevention of mother-to-child transmission (PMTCT) care continuum that defines the programmatic steps necessary to provide HIV care to the HIV-infected pregnant woman and her infant during the risk period for HIV transmission. RECENT FINDINGS: There are several complexities of PMTCT care that should be considered in the care continuum, including the evolution in the population of women entering PMTCT care, various models of PMTCT service delivery and patterns of PMTCT care, and the critical step of transfer of women's HIV care from PMTCT programs to adult HIV clinics. SUMMARY: We propose a reconceptualized PMTCT care continuum that accounts for the complexities of PMTCT care. We also propose a combined outcome for pregnant women and their infants across an interlinked PMTCT continuum to measure both maternal and child health outcomes. PMID- 26352392 TI - Geographical targeting to improve progression through the sexually transmitted infection/HIV treatment continua in different populations. AB - PURPOSE OF REVIEW: The purpose of this study is to review and synthesize the recent literature on the use of geographical targeting to improve progression through HIV and sexually transmitted disease (STD) prevention and treatment continua in different populations. RECENT FINDINGS: Geographical targeting can help identify obstacles to progression through prevention and treatment continua for each stage and in specific geographic locations. Macro-level geographical targeting can help maximize allocative efficiency, while micro-level targeting of hot spots increases effectiveness of interventions. Migration into and out of geographical areas of interest constitutes a challenge to geographical targeting in that stage-specific monitoring strategies tend to yield inaccurate results when people leave the area. Despite these issues, it is possible to identify failures in each stage of the continuum by specific spatial location such as census tracts and focus improvement efforts accordingly. SUMMARY: Vulnerabilities, risk behaviours and infections all cluster across age, race ethnicity, socioeconomic status, key populations, risk networks and geographic space. Spatial concentration may be the most important in this context, as it allows prevention programmes to identify and reach target populations more easily. Geographical targeting can be employed at both macro and micro levels and in combination with targeting of key populations and high-risk networks. PMID- 26352394 TI - Mobile health applications for HIV prevention and care in Africa. AB - PURPOSE OF REVIEW: More people have mobile phones in Africa than at any point in history. Mobile health (m-health), the use of mobile phones to support the delivery of health services, has expanded in recent years. Several models have been proposed for conceptualizing m-health in the fields of maternal-child health and chronic diseases. We conducted a literature review of m-health interventions for HIV prevention and care in African countries and present the findings in the context of a simplified framework. RECENT FINDINGS: Our review identified applications of m-health for HIV prevention and care categorized by the following three themes: patient-care focused applications, such as health behavior change, health system-focused applications, such as reporting and data collection, and population health-focused applications, including HIV awareness and testing campaigns. SUMMARY: The potential for m-health in Africa is numerous and should not be limited only to direct patient-care focused applications. Although the use of smart phone technology is on the rise in Africa, text messaging remains the primary mode of delivering m-health interventions. The rate at which mobile phone technologies are being adopted may outpace the rate of evaluation. Other methods of evaluation should be considered beyond only randomized-controlled trials. PMID- 26352393 TI - HIV treatment cascade in MSM, people who inject drugs, and sex workers. AB - PURPOSE OF REVIEW: People who inject drugs (PWID), sex workers, and MSM simultaneously bear a high burden of HIV and stigma and discrimination. The purpose of this review was to summarize recent information about the understanding of the HIV care cascade among PWID, sex workers, and MSM populations around the globe. RECENT FINDINGS: A review of the published literature relating to the care cascade in these three key populations was conducted. Data on the care cascade among key populations are sparse, particularly for PWID and sex workers. In the 12 countries in which a study or report of the care cascade was available stratified by these populations, all three populations have care cascade outcomes that are far below the 90-90-90 target set by the Joint United Nations Programme on HIV/AIDS (UNAIDS) for 2020. Culturally tailored interventions, including colocation of services and peer navigators, can improve care cascade outcomes among key populations. SUMMARY: Key populations' care cascade outcomes must be included in international reporting metrics to expand cascade data for these groups. Improving care cascade outcomes in these key populations through culturally tailored interventions should be a priority in the coming years. PMID- 26352395 TI - An update on the HIV treatment cascade in children and adolescents. AB - PURPOSE OF REVIEW: To provide an update on the HIV treatment cascade in children and adolescents. We reviewed the literature on the steps in the cascade, for the period 2014-2015. RECENT FINDINGS: There remains high attrition of children with regards to early testing and linking those patients who are positive to early treatment. Barriers to screening and testing in children and adolescents are multifactorial. Linkage to pre-antiretroviral therapy care and retention in care are the main steps at which attrition occurs. There are a number of new formulations available for use in adolescents and children which offer more options for antiretroviral therapy treatment. Adherence levels appear to be reasonable in Africa and Asia; however, achieving viral load suppression remains a challenge. SUMMARY: We have a long way to go to achieve decreased attrition at each step of the cascade and retain patients in care. Recent improvements in each step of the cascade are bringing us closer to achieving treatment success. PMID- 26352396 TI - HIV treatment cascade in migrants and mobile populations. AB - PURPOSE OF REVIEW: Health policy makers aspire to achieve an HIV treatment 'cascade' in which diagnostic and treatment services are accessed early and routinely by HIV-infected individuals. However, migrants and highly mobile individuals are likely to interact with HIV treatment programs and the healthcare system in ways that reflect their movement through time and place, affecting their successful progression through the HIV treatment cascade. We review recent research that has examined the challenges in effective and sustained HIV treatment for migrants and mobile populations. RECENT FINDINGS: Mobility is associated with increased risk of antiretroviral therapy (ART) nonadherence, lost to follow-up, deterioration in CD4 count, HIV-related death, development of drug resistance and general noncontinuity of HIV care. Migrants' slow progression through the HIV treatment cascade can be attributed to feelings of confusion, helplessness; an inability to effectively communicate in the native language; poor knowledge about administrative or logistical requirements of the healthcare system; the possibility of deportation or expulsion based on the legal status of the undocumented migrant; fear of disclosure and social isolation from the exile or compatriot group. Travel or transition to the host country commonly makes it difficult for migrants to remain enrolled in ART programs and to maintain adherence to treatment. SUMMARY: Existing public health systems fail to properly account for migration, and actionable knowledge of the health requirements of migrants is still lacking. A large body of research has shown that migrants are more likely to enter into the healthcare system late and are less likely to be retained at successive stages of the HIV treatment cascade. HIV-infected migrants are especially vulnerable to a wide range of social, economic and political factors that include a lack of direct access to healthcare services; exposure to difficult or oppressive work environments; the separation from family, friends and a familiar sociocultural environment. Realizing the full treatment and preventive benefits of the UNAIDS 90-90-90 strategy will require reaching all marginalized subpopulations of which migrants are a particularly large and important group. PMID- 26352397 TI - Changing models of care to improve progression through the HIV treatment cascade in different populations. AB - PURPOSE OF REVIEW: With global guidelines recommending earlier treatment for HIV infection, there will be increased demand for care and treatment services. Although health systems delivering HIV care globally have made advances in decentralizing to lower level health centers and enabling nurse-based delivery of antiretroviral treatment, they remain largely clinic based. Innovators have recently developed newer community-based care delivery models that could extend the capacity of stretched health systems to accommodate further increases in patient volumes. This review will focus on the programme outcomes from new care models and consider their ability to have an impact at scale. RECENT FINDINGS: Numerous patient-centered models of care have been developed to target patients stable on treatment and minimize clinic utilization. In rural areas, these models are aimed at reducing travel times and related costs, whereas models in urban and semi-urban areas focus on decreasing clinic congestion and patient wait times. Each of these models benefits from a focus on community support, and they demonstrate excellent retention in the care cascade for patients self-selecting into them. SUMMARY: Care models including nontraditional community-oriented care for well patients, largely delivered through nonmedical providers have demonstrated outstanding outcomes, and need to be further tested and scaled. PMID- 26352398 TI - Prevalence of Domestic Violence Among Trauma Patients. AB - IMPORTANCE: Domestic violence is an extremely underreported crime and a growing social problem in the United States. However, the true burden of the problem remains unknown. OBJECTIVE: To assess the reported prevalence of domestic violence among trauma patients. DESIGN, SETTING, AND PARTICIPANTS: A 6-year (2007 2012) retrospective analysis of the prospectively maintained National Trauma Data Bank. Trauma patients who experienced domestic violence and who presented to trauma centers participating in the National Trauma Data Bank were identified using International Classification of Diseases, Ninth Revision diagnosis codes (995.80-995.85, 995.50, 995.52-995.55, and 995.59) and E codes (E967.0-E967.9). Patients were stratified by age into 3 groups: children (<=18 years), adults (19 54 years), and elderly patients (>=55 years). Trend analysis was performed on April 10, 2014, to assess the reported prevalence of domestic violence over the years. PARTICIPANTS: Trauma patients presenting to trauma centers participating in the National Trauma Data Bank. MAIN OUTCOMES AND MEASURES: To assess the reported prevalence of domestic violence among trauma patients. RESULTS: A total of 16 575 trauma patients who experienced domestic violence were included. Of these trauma patients, 10 224 (61.7%) were children, 5503 (33.2%) were adults, and 848 (5.1%) were elderly patients. The mean (SD) age was 15.9 (20.6), the mean (SD) Injury Severity Score was 10.9 (9.6), and 8397 (50.7%) were male patients. Head injuries (46.8% of patients) and extremity fractures (31.2% of patients) were the most common injuries. A total of 12 515 patients (75.1%) were discharged home, and the overall mortality rate was 5.9% (n = 980). The overall reported prevalence of domestic violence among trauma patients was 5.7 cases per 1000 trauma center discharges. The prevalence of domestic violence increased among children (14.0 cases per 1000 trauma center discharges in 2007 to 18.5 case per 1000 trauma center discharges in 2012; P = .001) and adults (3.2 cases per 1000 discharges in 2007 to 4.5 cases per 1000 discharges in 2012; P = .001) over the 6 year period and remained unchanged for elderly patients (0.8 cases per 1000 discharges in 2007 to 0.96 cases per 1000 discharges in 2012; P = .09). On subanalysis of adults and elderly patients, the prevalence of domestic violence increased among both female (4.6 cases per 1000 discharges in 2007 to 5.3 cases per 1000 discharges in 2012; P = .001) and male patients (1.5 cases per 1000 discharges in 2007 to 2.8 cases per 1000 discharges in 2012; P = .001). CONCLUSIONS AND RELEVANCE: Domestic violence is prevalent among trauma patients. Over the years, the reported prevalence of domestic violence has been increasing among children and adults, and continues to remain high among female trauma patients. A robust mandatory screening for evaluating domestic violence among trauma patients, along with a focused national intervention, is warranted. PMID- 26352399 TI - Low Resting Heart Rate as an Unequivocal Risk Factor for Both the Perpetration of and Exposure to Violence. PMID- 26352400 TI - Do hospitals that do the right thing have more satisfied patients? AB - BACKGROUND: Hospital incentive payments are increasingly becoming tied to quality. However, the U.S. health care system continues to face rising health care costs and scarce workforce resources, making improving quality a challenge. Patient satisfaction and process quality are two areas of quality tied to reimbursement. Both are associated with positive health outcomes, but little is known about the relationship between the two. PURPOSES: The purpose of this study is to determine if there is an association between process quality and patient satisfaction in a representative sample of U.S. hospitals. METHODOLOGY/APPROACH: We utilize a pooled cross-sectional study design with year fixed effects from 2009 to 2011. We linked the Hospital Compare data set and the American Hospital Association Annual Survey of Hospitals (AHA) data set. We use a method prescribed by the Joint Commission to determine hospital-level process quality in three areas: heart failure, acute myocardial infarction, and pneumonia treatment. We then use regression models to measure the relationship between process quality and two measures of overall hospital patient satisfaction. FINDINGS: After we control for hospital-level characteristics and year, we find that patient satisfaction is positively associated with all three areas of hospital process quality (p < .01). For example, acute myocardial infarction process quality was positively associated with whether patients "would definitely recommend the hospital" (B = 0.75, p < .01). Process quality areas were moderately and positively correlated (p < .01), and on average, patient satisfaction scores have increased over time (p < .01). PRACTICE IMPLICATIONS: Our findings of an association between process quality and patient satisfaction suggest that focusing on process quality does not have negative implications for patient satisfaction. As performance in different process quality areas is only moderately correlated, managers should continually monitor all areas. The trend of increased patient satisfaction over time, perhaps because of industry pressures, should be investigated further. PMID- 26352401 TI - Rapid assessment of human amylin aggregation and its inhibition by copper(II) ions by laser ablation electrospray ionization mass spectrometry with ion mobility separation. AB - Native electrospray ionization (ESI) mass spectrometry (MS) is often used to monitor noncovalent complex formation between peptides and ligands. The relatively low throughput of this technique, however, is not compatible with extensive screening. Laser ablation electrospray ionization (LAESI) MS combined with ion mobility separation (IMS) can analyze complex formation and provide conformation information within a matter of seconds. Islet amyloid polypeptide (IAPP) or amylin, a 37-amino acid residue peptide, is produced in pancreatic beta cells through proteolytic cleavage of its prohormone. Both amylin and its precursor can aggregate and produce toxic oligomers and fibrils leading to cell death in the pancreas that can eventually contribute to the development of type 2 diabetes mellitus. The inhibitory effect of the copper(II) ion on amylin aggregation has been recently discovered, but details of the interaction remain unknown. Finding other more physiologically tolerated approaches requires large scale screening of potential inhibitors. Here, we demonstrate that LAESI-IMS-MS can reveal the binding stoichiometry, copper oxidation state, and the dissociation constant of human amylin-copper(II) complex. The conformations of hIAPP in the presence of copper(II) ions were also analyzed by IMS, and preferential association between the beta-hairpin amylin monomer and the metal ion was found. The copper(II) ion exhibited strong association with the -HSSNN- residues of the amylin. In the absence of copper(II), amylin dimers were detected with collision cross sections consistent with monomers of beta-hairpin conformation. When copper(II) was present in the solution, no dimers were detected. Thus, the copper(II) ions disrupt the association pathway to the formation of beta-sheet rich amylin fibrils. Using LAESI-IMS-MS for the assessment of amylin-copper(II) interactions demonstrates the utility of this technique for the high-throughput screening of potential inhibitors of amylin oligomerization and fibril formation. More generally, this rapid technique opens the door for high-throughput screening of potential inhibitors of amyloid protein aggregation. PMID- 26352402 TI - High expression of Midkine (MK) indicates poor prognosis in childhood acute lymphoblastic leukemia. AB - OBJECTIVES: Midkine (MK) expression has been reported to be correlated with the poor prognosis of patients with various tumors. However, there are no data available about the prognostic value of MK expression in childhood acute lymphoblastic leukemia (ALL). METHODS: In this study, MK mRNA expression was determined by real-time polymerase chain reaction in 120 childhood ALL and 30 healthy volunteers. Patients were dichotomized at the median value and divided into two groups: MK(low) group and MK(high) group. RESULTS: MK(high) patients had higher white blood cell counts, higher peripheral blood blasts percentages, and higher minimal residual disease levels than MK(low) patients. Moreover, the MK gene was expressed significantly higher in patients with relapsed ALL than in patients who maintained complete remission or at diagnosis. MK(high) patients harbored inferior relapse-free survival (RFS, P = 0.047) and overall survival (OS, P = 0.022) than MK(low) patients, and high expression of MK was found to be independently predictive of inferior OS (P = 0.032) but not RFS (P = 0.077) in the overall cohort. CONCLUSION AND DISCUSSION: MK high expression is an independent adverse prognostic factor in childhood ALL. Its level may be incorporated into an improved risk classification system for ALL and suggest the need of alternative regimens. PMID- 26352403 TI - Computer-Tailored Student Support in Introductory Physics. AB - Large introductory courses are at a disadvantage in providing personalized guidance and advice for students during the semester. We introduce E2Coach (an Expert Electronic Coaching system), which allows instructors to personalize their communication with thousands of students. We describe the E2Coach system, the nature of the personalized support it provides, and the features of the students who did (and did not) opt-in to using it during the first three terms of its use in four introductory physics courses at the University of Michigan. Defining a 'better-than-expected' measure of performance, we compare outcomes for students who used E2Coach to those who did not. We found that moderate and high E2Coach usage was associated with improved performance. This performance boost was prominent among high users, who improved by 0.18 letter grades on average when compared to nonusers with similar incoming GPAs. This improvement in performance was comparable across both genders. E2Coach represents one way to use technology to personalize education at scale, contributing to the move towards individualized learning that is becoming more attainable in the 21st century. PMID- 26352404 TI - Noninvasive Evaluation of Metabolic Tumor Volume in Lewis Lung Carcinoma Tumor Bearing C57BL/6 Mice with Micro-PET and the Radiotracers 18F-Alfatide and 18F FDG: A Comparative Analysis. AB - PURPOSE: To explore the value of a new simple lyophilized kit for labeling PRGD2 peptide (18F-ALF-NOTA-PRGD2, denoted as 18F-alfatide) in the determination of metabolic tumor volume (MTV) with micro-PET in lewis lung carcinoma (LLC) tumor bearing C57BL/6 mice verified by pathologic examination and compared with those using 18F-fluorodeoxyglucose (FDG) PET. METHODS: All LLC tumor-bearing C57BL/6 mice underwent two attenuation-corrected whole-body micro-PET scans with the radiotracers 18F-alfatide and 18F-FDG within two days. 18F-alfatide metabolic tumor volume (VRGD) and 18F-FDG metabolic tumor volume (VFDG) were manually delineated slice by slice on PET images. Pathologic tumor volume (VPath) was measured in vitro after the xenografts were removed. RESULTS: A total of 37 mice with NSCLC xenografts were enrolled and 33 of them underwent 18F-alfatide PET, and 35 of them underwent 18F-FDG PET and all underwent pathological examination. The mean +/- standard deviation of VPath, VRGD, and VFDG were 0.59+/-0.32 cm3 (range,0.13~1.64 cm3), 0.61+/-0.37 cm3 (range,0.15~1.86 cm3), and 1.24+/-0.53 cm3 (range,0.17~2.20 cm3), respectively. VPath vs. VRGD, VPath vs. VFDG, and VRGD vs. VFDG comparisons were t = -0.145, P = 0.885, t = -6.239, P<0.001, and t = -5.661, P<0.001, respectively. No significant difference was found between VPath and VRGD. VFDG was much larger than VRGD and VPath. VRGD seemed more approximate to the pathologic gross tumor volume. Furthermore, VPath was more strongly correlated with VRGD (R = 0.964,P<0.001) than with VFDG (R = 0.584,P<0.001). CONCLUSIONS: 18F-alfatide PET provided a better estimation of gross tumor volume than 18F-FDG PET in LLC tumor-bearing C57BL/6 mice. PMID- 26352405 TI - Finding Risk Groups by Optimizing Artificial Neural Networks on the Area under the Survival Curve Using Genetic Algorithms. AB - We investigate a new method to place patients into risk groups in censored survival data. Properties such as median survival time, and end survival rate, are implicitly improved by optimizing the area under the survival curve. Artificial neural networks (ANN) are trained to either maximize or minimize this area using a genetic algorithm, and combined into an ensemble to predict one of low, intermediate, or high risk groups. Estimated patient risk can influence treatment choices, and is important for study stratification. A common approach is to sort the patients according to a prognostic index and then group them along the quartile limits. The Cox proportional hazards model (Cox) is one example of this approach. Another method of doing risk grouping is recursive partitioning (Rpart), which constructs a decision tree where each branch point maximizes the statistical separation between the groups. ANN, Cox, and Rpart are compared on five publicly available data sets with varying properties. Cross-validation, as well as separate test sets, are used to validate the models. Results on the test sets show comparable performance, except for the smallest data set where Rpart's predicted risk groups turn out to be inverted, an example of crossing survival curves. Cross-validation shows that all three models exhibit crossing of some survival curves on this small data set but that the ANN model manages the best separation of groups in terms of median survival time before such crossings. The conclusion is that optimizing the area under the survival curve is a viable approach to identify risk groups. Training ANNs to optimize this area combines two key strengths from both prognostic indices and Rpart. First, a desired minimum group size can be specified, as for a prognostic index. Second, the ability to utilize non-linear effects among the covariates, which Rpart is also able to do. PMID- 26352408 TI - Introduction: GABAergic neurotransmission in the human cerebral cortex: same rules apply? PMID- 26352406 TI - Intrahepatic Transcriptional Signature Associated with Response to Interferon alpha Treatment in the Woodchuck Model of Chronic Hepatitis B. AB - Recombinant interferon-alpha (IFN-alpha) is an approved therapy for chronic hepatitis B (CHB), but the molecular basis of treatment response remains to be determined. The woodchuck model of chronic hepatitis B virus (HBV) infection displays many characteristics of human disease and has been extensively used to evaluate antiviral therapeutics. In this study, woodchucks with chronic woodchuck hepatitis virus (WHV) infection were treated with recombinant woodchuck IFN-alpha (wIFN-alpha) or placebo (n = 12/group) for 15 weeks. Treatment with wIFN-alpha strongly reduced viral markers in the serum and liver in a subset of animals, with viral rebound typically being observed following cessation of treatment. To define the intrahepatic cellular and molecular characteristics of the antiviral response to wIFN-alpha, we characterized the transcriptional profiles of liver biopsies taken from animals (n = 8-12/group) at various times during the study. Unexpectedly, this revealed that the antiviral response to treatment did not correlate with intrahepatic induction of the majority of IFN-stimulated genes (ISGs) by wIFN-alpha. Instead, treatment response was associated with the induction of an NK/T cell signature in the liver, as well as an intrahepatic IFN gamma transcriptional response and elevation of liver injury biomarkers. Collectively, these data suggest that NK/T cell cytolytic and non-cytolytic mechanisms mediate the antiviral response to wIFN-alpha treatment. In summary, by studying recombinant IFN-alpha in a fully immunocompetent animal model of CHB, we determined that the immunomodulatory effects, but not the direct antiviral activity, of this pleiotropic cytokine are most closely correlated with treatment response. This has important implications for the rational design of new therapeutics for the treatment of CHB. PMID- 26352407 TI - Genome-Wide Association Study with Targeted and Non-targeted NMR Metabolomics Identifies 15 Novel Loci of Urinary Human Metabolic Individuality. AB - Genome-wide association studies with metabolic traits (mGWAS) uncovered many genetic variants that influence human metabolism. These genetically influenced metabotypes (GIMs) contribute to our metabolic individuality, our capacity to respond to environmental challenges, and our susceptibility to specific diseases. While metabolic homeostasis in blood is a well investigated topic in large mGWAS with over 150 known loci, metabolic detoxification through urinary excretion has only been addressed by few small mGWAS with only 11 associated loci so far. Here we report the largest mGWAS to date, combining targeted and non-targeted 1H NMR analysis of urine samples from 3,861 participants of the SHIP-0 cohort and 1,691 subjects of the KORA F4 cohort. We identified and replicated 22 loci with significant associations with urinary traits, 15 of which are new (HIBCH, CPS1, AGXT, XYLB, TKT, ETNPPL, SLC6A19, DMGDH, SLC36A2, GLDC, SLC6A13, ACSM3, SLC5A11, PNMT, SLC13A3). Two-thirds of the urinary loci also have a metabolite association in blood. For all but one of the 6 loci where significant associations target the same metabolite in blood and urine, the genetic effects have the same direction in both fluids. In contrast, for the SLC5A11 locus, we found increased levels of myo-inositol in urine whereas mGWAS in blood reported decreased levels for the same genetic variant. This might indicate less effective re-absorption of myo inositol in the kidneys of carriers. In summary, our study more than doubles the number of known loci that influence urinary phenotypes. It thus allows novel insights into the relationship between blood homeostasis and its regulation through excretion. The newly discovered loci also include variants previously linked to chronic kidney disease (CPS1, SLC6A13), pulmonary hypertension (CPS1), and ischemic stroke (XYLB). By establishing connections from gene to disease via metabolic traits our results provide novel hypotheses about molecular mechanisms involved in the etiology of diseases. PMID- 26352409 TI - Structural and neurochemical correlates of individual differences in gamma frequency oscillations in human visual cortex. AB - Neuronal oscillations in the gamma frequency range play an important role in stimulus processing in the brain. The frequency of these oscillations can vary widely between participants and is strongly genetically determined, but the cause of this variability is not understood. Previous studies have reported correlations between individual differences in gamma frequency and the concentration of the inhibitory neurotransmitter, gamma-aminobutyric acid (GABA), as well as with age and primary visual cortex (V1) area and thickness. This study assessed the relationships between all of these variables in the same group of participants. There were no significant correlations between gamma frequency and GABA+ concentration, V1 area or V1 thickness, although the relationship with GABA+/Cr approached significance. Considering age as a covariate further reduced the strength of all correlations and, in an additional dataset with a larger age range, gamma frequency was strongly inversely correlated with age but not V1 thickness or area, suggesting that age modulates gamma frequency via an additional, as yet unknown, mechanism. Consistent with other recent studies, these findings do not demonstrate a clear relationship between gamma frequency and GABA+ concentration. Further investigation of additional variables and the interactions between them will be necessary in order to more accurately determine predictors of the frequency of gamma oscillations. PMID- 26352410 TI - Topography and extent of pulmonary vagus nerve supply with respect to transthoracic oesophagectomy. AB - Pulmonary complications are frequently observed after transthoracic oesophagectomy. These complications may be reduced by sparing the vagus nerve branches to the lung. However, current descriptions of the regional anatomy are insufficient. Therefore, we aimed to provide a highly detailed description of the course of the pulmonary vagus nerve branches. In six fixed adult human cadavers, bilateral microscopic dissection of the vagus nerve branches to the lungs was performed. The level of branching and the number, calibre and distribution of nerve branches were described. Nerve fibres were identified using neurofilament immunohistochemistry, and the nerve calibre was measured using computerized image analysis. Both lungs were supplied by a predominant posterior and a smaller anterior nerve plexus. The right lung was supplied by 13 (10-18) posterior and 3 (2-3) anterior branches containing 77% (62-100%) and 23% (0-38%) of the lung nerve supply, respectively. The left lung was supplied by a median of 12 (8-13) posterior and 3 (2-4) anterior branches containing 74% (60-84%) and 26% (16-40%) of the left lung nerve supply, respectively. During transthoracic oesophagectomy with en bloc lymphadenectomy and transection of the vagus nerves at the level of the azygos vein, 68-100% of the right lung nerve supply and 86-100% of the inferior left lung lobe nerve supply were severed. When vagotomy was performed distally to the last large pulmonary branch, 0-8% and 0-13% of the nerve branches to the right middle/inferior lobes and left inferior lobe, respectively, were lost. In conclusion, this study provides a detailed description of the extensive pulmonary nerve supply provided by the vagus nerves. During oesophagectomy, extensive mediastinal lymphadenectomy denervates the lung to a great extent; however, this can be prevented by performing the vagotomy distal to the caudalmost large pulmonary branch. Further research is required to determine the feasibility of sparing the pulmonary vagus nerve branches without compromising the completeness of lymphadenectomy. PMID- 26352412 TI - Accelerating Neuroimage Registration through Parallel Computation of Similarity Metric. AB - Neuroimage registration is crucial for brain morphometric analysis and treatment efficacy evaluation. However, existing advanced registration algorithms such as FLIRT and ANTs are not efficient enough for clinical use. In this paper, a GPU implementation of FLIRT with the correlation ratio (CR) as the similarity metric and a GPU accelerated correlation coefficient (CC) calculation for the symmetric diffeomorphic registration of ANTs have been developed. The comparison with their corresponding original tools shows that our accelerated algorithms can greatly outperform the original algorithm in terms of computational efficiency. This paper demonstrates the great potential of applying these registration tools in clinical applications. PMID- 26352411 TI - Ultrastructure of dragonfly wing veins: composite structure of fibrous material supplemented by resilin. AB - Dragonflies count among the most skilful of the flying insects. Their exceptional aerodynamic performance has been the subject of various studies. Morphological and kinematic investigations have showed that dragonfly wings, though being rather stiff, are able to undergo passive deformation during flight, thereby improving the aerodynamic performance. Resilin, a rubber-like protein, has been suggested to be a key component in insect wing flexibility and deformation in response to aerodynamic loads, and has been reported in various arthropod locomotor systems. It has already been found in wing vein joints, connecting longitudinal veins to cross veins, and was shown to endow the dragonfly wing with chordwise flexibility, thereby most likely influencing the dragonfly's flight performance. The present study revealed that resilin is not only present in wing vein joints, but also in the internal cuticle layers of veins in wings of Sympetrum vulgatum (SV) and Matrona basilaris basilaris (MBB). Combined with other structural features of wing veins, such as number and thickness of cuticle layers, material composition, and cross-sectional shape, resilin most probably has an effect on the vein's material properties and the degree of elastic deformations. In order to elucidate the wing vein ultrastructure and the exact localisation of resilin in the internal layers of the vein cuticle, the approaches of bright-field light microscopy, wide-field fluorescence microscopy, confocal laser-scanning microscopy, scanning electron microscopy and transmission electron microscopy were combined. Wing veins were shown to consist of up to six different cuticle layers and a single row of underlying epidermal cells. In wing veins of MBB, the latter are densely packed with light-scattering spheres, previously shown to produce structural colours in the form of quasiordered arrays. Longitudinal and cross veins differ significantly in relative thickness of exo- and endocuticle, with cross veins showing a much thicker exocuticle. The presence of resilin in the unsclerotised endocuticle suggests its contribution to an increased energy storage and material flexibility, thus to the prevention of vein damage. This is especially important in the highly stressed longitudinal veins, which have much lower possibility to yield to applied loads with the aid of vein joints, as the cross veins do. These results may be relevant not only for biologists, but may also contribute to optimise the design of micro-air vehicles. PMID- 26352414 TI - Correction: Genomic Comparison of Non-Typhoidal Salmonella enterica Serovars Typhimurium, Enteritidis, Heidelberg, Hadar and Kentucky Isolates from Broiler Chickens. PMID- 26352413 TI - Biomechanical Diversity of Mating Structures among Harvestmen Species Is Consistent with a Spectrum of Precopulatory Strategies. AB - Diversity in reproductive structures is frequently explained by selection acting at individual to generational timescales, but interspecific differences predicted by such models (e.g., female choice or sexual conflict) are often untestable in a phylogenetic framework. An alternative approach focuses on clade- or function specific hypotheses that predict evolutionary patterns in terms neutral to specific modes of sexual selection. Here we test a hypothesis that diversity of reproductive structures in leiobunine harvestmen (daddy longlegs) of eastern North America reflects two sexually coevolved but non-overlapping precopulatory strategies, a primitive solicitous strategy (females enticed by penis-associated nuptial gifts), and a multiply derived antagonistic strategy (penis exerts mechanical force against armature of the female pregenital opening). Predictions of sexual coevolution and fidelity to precopulatory categories were tested using 10 continuously varying functional traits from 28 species. Multivariate analyses corroborated sexual coevolution but failed to partition species by precopulatory strategy, with multiple methods placing species along a spectrum of mechanical antagonistic potential. These findings suggest that precopulatory features within species reflect different co-occurring levels of solicitation and antagonism, and that gradualistic evolutionary pathways exist between extreme strategies. The ability to quantify antagonistic potential of precopulatory structures invites comparison with ecological variables that may promote evolutionary shifts in precopulatory strategies. PMID- 26352415 TI - Income Inequality, Economic Growth and Stroke Mortality in Brazil: Longitudinal and Regional Analysis 2002-2009. AB - BACKGROUND AND PURPOSE: Stroke accounts for more than 10% of all deaths globally and most of it occurs in low- and middle-income countries (LMIC). Income inequality and gross domestic product (GDP) per capita has been associated to stroke mortality in developed countries. In LMIC, GDP per capita is considered to be a more relevant health determinant than income inequality. This study aims to investigate if income inequality is associated to stroke mortality in Brazil at large, but also on regional and state levels, and whether GDP per capita modulates the impact of this association. METHODS: Stroke mortality rates, Gini index and GDP per capita data were pooled for the 2002 to 2009 period from public available databases. Random effects models were fitted, controlling for GDP per capita and other covariates. RESULTS: Income inequality was independently associated to stroke mortality rates, even after controlling for GDP per capita and other covariates. GDP per capita reduced only partially the impact of income inequality on stroke mortality. A decrease in 10 points in the Gini index was associated with 18% decrease in the stroke mortality rate in Brazil. CONCLUSIONS: Income inequality was independently associated to stroke mortality in Brazil. PMID- 26352416 TI - Two-dimensional nanosheets of MoS2: a promising material with high dielectric properties and microwave absorption performance. AB - In this study, few-layered MoS2 nanosheets (MoS2-NS) were obtained via the top down exfoliation method from bulk MoS2 (MoS2-Bulk), and the dielectric properties and microwave absorption performance of MoS2-NS were first reported. The dimension-dependent dielectric properties and microwave absorption performance of MoS2 were investigated by presenting a comparative study between MoS2-NS and MoS2 Bulk. Our results show that the imaginary permittivity (epsilon'') of MoS2-NS/wax is twice as large as that of MoS2-Bulk/wax. The minimum reflection loss (RL) value of MoS2-NS/wax with 60 wt% loading is -38.42 dB at a thickness of 2.4 mm, which is almost 4 times higher than that of MoS2-Bulk/wax, and the corresponding bandwidth with effective attenuation (<-10 dB) of MoS2-NS/wax is up to 4.1 GHz (9.6-13.76 GHz). The microwave absorption performance of MoS2-NS is comparable to those reported in carbon-related nanomaterials. The enhanced microwave absorption performance of MoS2-NS is attributed to the defect dipole polarization arising from Mo and S vacancies and its higher specific surface area. These results suggest that MoS2-NS is a promising candidate material not only in fundamental studies but also in practical microwave applications. PMID- 26352417 TI - Letter From the Editor: Lies and truth. PMID- 26352418 TI - The National Cancer Institute's Experimental Therapeutics Clinical Trials Network. PMID- 26352419 TI - The role of third-generation epithelial growth factor receptor inhibitors in non small cell lung cancer. PMID- 26352420 TI - The shifting paradigm for transfusion of red blood cells. PMID- 26352422 TI - Rituximab maintenance in follicular lymphoma. PMID- 26352423 TI - Counterpoints: Do patients with multiple myeloma need maintenance treatment? Yes, but the proper candidates and schedule must be determined. PMID- 26352424 TI - Counterpoints: Do patients with multiple myeloma need maintenance treatment? No, maintenance treatment should not be used outside clinical trials. PMID- 26352425 TI - Hepatocellular carcinoma: current questions and future directions. PMID- 26352426 TI - Key statistical concepts in cancer research. AB - In this article, we provide a high-level overview of statistical concepts related to study design and data analysis in oncology research. These concepts are discussed for 2 main types of clinical research: (1) observational studies, which focus on biomarker discovery in order to predict disease risk and prognosis, and (2) prospectively designed, well-controlled clinical trials, which are critical for the development of new cancer treatments. Throughout the article, we emphasize the importance of appropriate design and prospectively determined analysis plans. We also hope to promote effective collaboration between oncology investigators and statisticians who center their research on the development of cancer treatments. PMID- 26352427 TI - Review of treatment options for oligometastatic non-small cell lung cancer. AB - Our understanding of metastatic disease is constantly evolving. Although outcomes for patients with stage IV non-small cell lung cancer (NSCLC) are poor, aggressive/radical local intervention may be effective in a subset of patients with limited or "oligometastatic" disease. Here we review and compare the range of available treatment options that are specific to oligometastatic NSCLC, and discuss potential directions of future clinical research. PMID- 26352428 TI - Improved detection of diffuse large B-cell lymphoma by flow cytometric immunophenotyping-Effect of tissue disaggregation method. AB - BACKGROUND: Flow cytometric immunophenotyping (FCI) is recognized as a rapid, sensitive, and accurate method for diagnosis of B-cell lymphomas. We observed that FCI failed to identify the clonal B-cell population in several cases of large B-cell lymphoma (DLBCL) when tissue samples were prepared by a commercially available mechanical tissue disaggregation method. We tested a manual tissue disaggregation method and compared it with the mechanical method. METHODS: FCI findings from 51 cases of DLBCL processed with the mechanical tissue disaggregation method, 27 cases processed using the manual method, and 15 cases processed using a combination of both methods were compared. The histological and immunohistochemical findings in each case were reviewed. RESULTS: FCI detected a clonal B-cell population in 88.9% of cases processed by the manual tissue disaggregation method, 66.7% of cases processed by a combination of the manual and mechanical disaggregation methods, and in 62.7% of cases processed solely by the mechanical tissue disaggregation method (P < 0.01 Fisher exact). Manual processing yielded positive FCI results in 81.8% of the nodal tissue samples and 93.8% of the extra-nodal tissue samples, whereas mechanical disaggregation was particularly inefficient in preserving large lymphoma cells from extra-nodal tissue: 71.4% of the nodal and 56.8% of the extra-nodal tissue samples processed by the mechanical method showed clonal B-cells by flow cytometry (P < 0.006, Fisher exact). CONCLUSIONS: The diagnostic yield of FCI in DLBCL can be significantly improved by utilizing a manual disaggregation method, particularly in extra-nodal tissue samples. (c) 2015 International Clinical Cytometry Society. PMID- 26352429 TI - Vocalisations of Killer Whales (Orcinus orca) in the Bremer Canyon, Western Australia. AB - To date, there has been no dedicated study in Australian waters on the acoustics of killer whales. Hence no information has been published on the sounds produced by killer whales from this region. Here we present the first acoustical analysis of recordings collected off the Western Australian coast. Underwater sounds produced by Australian killer whales were recorded during the months of February and March 2014 and 2015 in the Bremer Canyon in Western Australia. Vocalisations recorded included echolocation clicks, burst-pulse sounds and whistles. A total of 28 hours and 29 minutes were recorded and analysed, with 2376 killer whale calls (whistles and burst-pulse sounds) detected. Recordings of poor quality or signal-to-noise ratio were excluded from analysis, resulting in 142 whistles and burst-pulse vocalisations suitable for analysis and categorisation. These were grouped based on their spectrographic features into nine Bremer Canyon (BC) "call types". The frequency of the fundamental contours of all call types ranged from 600 Hz to 29 kHz. Calls ranged from 0.05 to 11.3 seconds in duration. Biosonar clicks were also recorded, but not studied further. Surface behaviours noted during acoustic recordings were categorised as either travelling or social behaviour. A detailed description of the acoustic characteristics is necessary for species acoustic identification and for the development of passive acoustic tools for population monitoring, including assessments of population status, habitat usage, migration patterns, behaviour and acoustic ecology. This study provides the first quantitative assessment and report on the acoustic features of killer whales vocalisations in Australian waters, and presents an opportunity to further investigate this little-known population. PMID- 26352430 TI - Astragalosides promote angiogenesis via vascular endothelial growth factor and basic fibroblast growth factor in a rat model of myocardial infarction. AB - The aim of the present study was to evaluate the effect of astragalosides (ASTs) on angiogenesis, as well as the expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) following myocardial infarction (MI). MI was induced in rats by ligation of the left coronary artery. Twenty-four hours after surgery, the rats were divided into low-dose, high-dose, control and sham surgery groups (n=8 per group). The low- and high-dose groups were treated with ASTs (2.5 and 10 mg/kg/day, respectively, via intraperitoneal injection), while, the control and sham surgery group rats received saline. Serum levels, and mRNA and protein expression levels of VEGF and bFGF, as well as the microvessel density (MVD) were determined four weeks post-treatment. Twenty-four hours post surgery, VEGF and bFGF serum levels were observed to be comparable between the groups; while at four weeks, the VEGF and bFGF levels were higher in the AST treated rats (P<0.01). Similarly, VEGF and bFGF mRNA and protein expression levels were higher following AST treatment (P<0.05). No difference in VEGF mRNA expression between the low- and high-dose groups was noted, however, an increase in the bFGF expression levels was detected in the high-dose group. Newly generated blood vessels were observed following MI, with a significant increase in MVD observed in the AST-treated groups (P<0.05). AST promotes angiogenesis of the heart and increases VEGF and bFGF expression levels. Thus, it is hypothesized that increased VEGF and bFGF levels may contribute to the AST-induced increase in angiogenesis in rat models of MI. PMID- 26352432 TI - Effect of Orbital Decompression on Corneal Topography in Patients with Thyroid Ophthalmopathy. AB - OBJECTIVE: To evaluate changes in corneal astigmatism in patients undergoing orbital decompression surgery. METHODS: This retrospective, non randomized comparative study involved 42 eyes from 21 patients with thyroid ophthalmopathy who underwent orbital decompression surgery between September 2011 and September 2014. The 42 eyes were divided into three groups: control (9 eyes), two-wall decompression (25 eyes), and three-wall decompression (8 eyes). The control group was defined as the contralateral eyes of nine patients who underwent orbital decompression surgery in only one eye. Corneal topography (Orbscan II), Hertel exophthalmometry, and intraocular pressure were measured at 1 month before and 3 months after surgery. Corneal topographic parameters analyzed were total astigmatism (TA), steepest axis (SA), central corneal thickness (CCT), and anterior chamber depth (ACD). RESULTS: Exophthalmometry values and intraocular pressure decreased significantly after the decompression surgery. The change (absolute value (|x|) of the difference) in astigmatism at the 3 mm zone was significantly different between the decompression group and the controls (p = 0.025). There was also a significant change in the steepest axis at the 3 mm zone between the decompression group and the controls (p = 0.033). An analysis of relevant changes in astigmatism showed that there was a dominant tendency for incyclotorsion of the steepest axis in eyes that underwent decompression surgery. Using Astig PLOT, the mean surgically induced astigmatism (SIA) was 0.21+/-0.88 D with an axis of 46+/-22 degrees , suggesting that decompression surgery did change the corneal shape and induced incyclotorsion of the steepest axis. CONCLUSIONS: There was a significant change in corneal astigmatism after orbital decompression surgery and this change was sufficient to affect the optical function of the cornea. Surgeons and patients should be aware of these changes. PMID- 26352431 TI - HIF1alpha-Induced by Lysophosphatidic Acid Is Stabilized via Interaction with MIF and CSN5. AB - Macrophage migration inhibitory factor (MIF) is a cytokine that has broad effects on immune system and inflammatory response. A growing body of evidence implicates the role of MIF in tumor growth and metastasis. Lysophosphatidic acid (LPA), a bioactive lipid mediator, regulates colon cancer cell proliferation, invasion, and survival through LPA2 receptor. Loss of LPA2 results in decreased expression of MIF in a rodent model of colon cancer, but the mechanism of MIF regulation by LPA is yet to be determined. In this study, we show that LPA transcriptionally regulates MIF expression in colon cancer cells. MIF knockdown decreased LPA mediated proliferation of HCT116 human adenocarcinoma cells without altering the basal proliferation rates. Conversely, extracellular recombinant MIF stimulated cell proliferation, suggesting that the effect of MIF may in part be mediated through activation of surface receptor. We have shown recently that LPA increases hypoxia-inducible factor 1alpha (HIF1alpha) expression. We found that MIF regulation by LPA was ablated by knockdown of HIF1alpha, indicating that MIF is a transcriptional target of HIF1alpha. Conversely, knockdown of MIF ablated an increase in HIF1alpha expression in LPA-treated cells, suggesting a reciprocal relationship between HIF1alpha and MIF. LPA stimulated co-immunoprecipitation of HIF1alpha and MIF, indicating that their association is necessary for stabilization of HIF1alpha. It has been shown previously that CSN9 signalosome subunit 5 (CSN5) interacts with HIF1alpha to stabilize HIF1alpha under aerobic conditions. We found that LPA did not alter expression of CSN5, but stimulated its interaction with HIF1alpha and MIF. Depletion of CSN5 mitigated the association between HIF1alpha and MIF, indicating that CSN5 acts as a physical link. We suggest that HIF1alpha, MIF, and CSN5 form a ternary complex whose formation is necessary to prevent degradation of HIF1alpha under aerobic conditions. PMID- 26352433 TI - Nutrient Dynamics of Estuarine Invertebrates Are Shaped by Feeding Guild Rather than Seasonal River Flow. AB - This study aimed to determine the variability of carbon and nitrogen elemental content, stoichiometry and diet proportions of invertebrates in two sub-tropical estuaries in South Africa experiencing seasonal changes in rainfall and river inflow. The elemental ratios and stable isotopes of abiotic sources, zooplankton and macrozoobenthos taxa were analyzed over a dry/wet seasonal cycle. Nutrient content (C, N) and stoichiometry of suspended particulate matter exhibited significant spatio-temporal variations in both estuaries, which were explained by the variability in river inflow. Sediment particulate matter (%C, %N and C:N) was also influenced by the variability in river flow but to a lesser extent. The nutrient content and ratios of the analyzed invertebrates did not significantly vary among seasons with the exception of the copepod Pseudodiaptomus spp. (C:N) and the tanaid Apseudes digitalis (%N, C:N). These changes did not track the seasonal variations of the suspended or sediment particulate matter. Our results suggest that invertebrates managed to maintain their stoichiometry independent of the seasonality in river flow. A significant variability in nitrogen content among estuarine invertebrates was recorded, with highest % N recorded from predators and lowest %N from detritivores. Due to the otherwise general lack of seasonal differences in elemental content and stoichiometry, feeding guild was a major factor shaping the nutrient dynamics of the estuarine invertebrates. The nutrient richer suspended particulate matter was the preferred food source over sediment particulate matter for most invertebrate consumers in many, but not all seasons. The most distinct preference for suspended POM as a food source was apparent from the temporarily open/closed system after the estuary had breached, highlighting the importance of river flow as a driver of invertebrate nutrient dynamics under extreme events conditions. Moreover, our data showed that estuarine invertebrates concentrated C and N between 10-100 fold from trophic level I (POM) to trophic level II (detritivores/deposit feeders) and thus highlighted their importance not only as links to higher trophic level organisms in the food web, but also as providers of a stoichiometrically homeostatic food source for such consumers. As climate change scenarios for the east coast of South Africa predict increased rainfall as a higher number of rainy days and days with higher rainfall, our results suggest that future changes in rainfall and river inflow will have measurable effects on the nutrient content and stoichiometry of food sources and possibly also in estuarine consumers. PMID- 26352434 TI - Indirect relativistic bridge and substituent effects from the 'heavy' environment on the one-bond and two-bond (13)C-(1)H spin-spin coupling constants. AB - Indirect relativistic bridge effect (IRBE) and indirect relativistic substituent effect (IRSE) induced by the 'heavy' environment of the IV-th, V-th and VI-th main group elements on the one-bond and geminal (13)C-(1)H spin-spin coupling constants are observed, and spin-orbit parts of these two effects were interpreted in terms of the third-order Rayleigh-Schrodinger perturbation theory. Both effects, IRBE and IRSE, rapidly increase with the total atomic charge of the substituents at the coupled carbon. The accumulation of IRSE for geminal coupling constants is not linear with respect to the number of substituents in contrast to the one-bond couplings where IRSE is an essentially additive quantity. PMID- 26352436 TI - Patterns and Predictors of Language and Literacy Abilities 4-10 Years in the Longitudinal Study of Australian Children. AB - AIMS: Oral language is the foundation of literacy. Naturally, policies and practices to promote children's literacy begin in early childhood and have a strong focus on developing children's oral language, especially for children with known risk factors for low language ability. The underlying assumption is that children's progress along the oral to literate continuum is stable and predictable, such that low language ability foretells low literacy ability. This study investigated patterns and predictors of children's oral language and literacy abilities at 4, 6, 8 and 10 years. The study sample comprised 2,316 to 2,792 children from the first nationally representative Longitudinal Study of Australian Children (LSAC). Six developmental patterns were observed, a stable middle-high pattern, a stable low pattern, an improving pattern, a declining pattern, a fluctuating low pattern, and a fluctuating middle-high pattern. Most children (69%) fit a stable middle-high pattern. By contrast, less than 1% of children fit a stable low pattern. These results challenged the view that children's progress along the oral to literate continuum is stable and predictable. FINDINGS: Multivariate logistic regression was used to investigate risks for low literacy ability at 10 years and sensitivity-specificity analysis was used to examine the predictive utility of the multivariate model. Predictors were modelled as risk variables with the lowest level of risk as the reference category. In the multivariate model, substantial risks for low literacy ability at 10 years, in order of descending magnitude, were: low school readiness, Aboriginal and/or Torres Strait Islander status and low language ability at 8 years. Moderate risks were high temperamental reactivity, low language ability at 4 years, and low language ability at 6 years. The following risk factors were not statistically significant in the multivariate model: Low maternal consistency, low family income, health care card, child not read to at home, maternal smoking, maternal education, family structure, temperamental persistence, and socio economic area disadvantage. The results of the sensitivity-specificity analysis showed that a well-fitted multivariate model featuring risks of substantive magnitude did not do particularly well in predicting low literacy ability at 10 years. PMID- 26352437 TI - Increased efficiency of testicular tumor chemotherapy by ultrasound microbubble mediated targeted transfection of siMDR1. AB - The MDR1 gene encoding P-glycoprotein (P-gp) is an ATP-dependent drug efflux transporter and is related to drug resistance of yolk sac tumors. Drug resistence may be an important factor for the low efficiency of chemotherapy in the treatment of testicular tumors. P-gp, encoded by the MDR1 gene, is an ATP-binding cassette transporter. P-gp exhibits high expression in capillary endothelial cells of the testis and prevents the intracellular accumulation of chemotherapy agents in testicular tumor cells, resulting in drug resistance. In the present study, we aimed to use specific siRNA to silence the expression of the MDR1 gene and P-gp, leading to the reversal of multidrug resistance of testicular tumors and contributing a suitable condition for chemotherapy. Ultrasound microbubble mediated delivery is a safe and effective tool for gene delivery. In the present study, we demonstrated that ultrasound microbubble-mediated delivery effectively improved the siMDR1 gene transfection in interstitial capillary endothelial cells of the testis, inhibited the expression of P-gp and increased daunorubicin accumulation. The testis tumor model was successfully constructed by injecting 1x10(7) yolk sac tumor cells in 3-week-old Sprague-Dawley rats. Ultrasound microbubble-mediated siMDR1 gene therapy improved the effect of chemotherapy on the testicular tumors. The testicular volume was reduced, the number of tumor cells within the testicular tissues decreased, and pathological changes were mostly recovered. Therefore, the present study indicated that ultrasound microbubble-mediated siMDR1 gene therapy in vivo reversed drug resistance by regulating P-gp expression, providing a promising method for the treatment of testicular tumors. PMID- 26352435 TI - Evolutionary History of the Photolyase/Cryptochrome Superfamily in Eukaryotes. AB - BACKGROUND: Photolyases and cryptochromes are evolutionarily related flavoproteins, which however perform distinct physiological functions. Photolyases (PHR) are evolutionarily ancient enzymes. They are activated by light and repair DNA damage caused by UV radiation. Although cryptochromes share structural similarity with DNA photolyases, they lack DNA repair activity. Cryptochrome (CRY) is one of the key elements of the circadian system in animals. In plants, CRY acts as a blue light receptor to entrain circadian rhythms, and mediates a variety of light responses, such as the regulation of flowering and seedling growth. RESULTS: We performed a comprehensive evolutionary analysis of the CRY/PHR superfamily. The superfamily consists of 7 major subfamilies: CPD class I and CPD class II photolyases, (6-4) photolyases, CRY-DASH, plant PHR2, plant CRY and animal CRY. Although the whole superfamily evolved primarily under strong purifying selection (average omega = 0.0168), some subfamilies did experience strong episodic positive selection during their evolution. Photolyases were lost in higher animals that suggests natural selection apparently became weaker in the late stage of evolutionary history. The evolutionary time estimates suggested that plant and animal CRYs evolved in the Neoproterozoic Era (~1000-541 Mya), which might be a result of adaptation to the major climate and global light regime changes occurred in that period of the Earth's geological history. PMID- 26352438 TI - A collaborative sequential meta-analysis of individual patient data from randomized trials of endovascular therapy and tPA vs. tPA alone for acute ischemic stroke: ThRombEctomy And tPA (TREAT) analysis: statistical analysis plan for a sequential meta-analysis performed within the VISTA-Endovascular collaboration. AB - RATIONALE: Endovascular treatment has been shown to restore blood flow effectively. Second-generation medical devices such as stent retrievers are now showing overwhelming efficacy in clinical trials, particularly in conjunction with intravenous recombinant tissue plasminogen activator. AIMS AND DESIGN: This statistical analysis plan utilizing a novel, sequential approach describes a prospective, individual patient data analysis of endovascular therapy in conjunction with intravenous recombinant tissue plasminogen activator agreed upon by the Thrombectomy and Tissue Plasminogen Activator Collaborative Group. STUDY OUTCOMES: This protocol will specify the primary outcome for efficacy, as 'favorable' outcome defined by the ordinal distribution of the modified Rankin Scale measured at three-months poststroke, but with modified Rankin Scales 5 and 6 collapsed into a single category. The primary analysis will aim to answer the questions: 'what is the treatment effect of endovascular therapy with intravenous recombinant tissue plasminogen activator compared to intravenous tissue plasminogen activator alone on full scale modified Rankin Scale at 3 months?' and 'to what extent do key patient characteristics influence the treatment effect of endovascular therapy?'. Key secondary outcomes include effect of endovascular therapy on death within 90 days; analyses of modified Rankin Scale using dichotomized methods; and effects of endovascular therapy on symptomatic intracranial hemorrhage. Several secondary analyses will be considered as well as expanding patient cohorts to intravenous recombinant tissue plasminogen activator ineligible patients, should data allow. DISCUSSION: This collaborative meta analysis of individual participant data from randomized trials of endovascular therapy vs. control in conjunction with intravenous thrombolysis will demonstrate the efficacy and generalizability of endovascular therapy with intravenous thrombolysis as a concomitant medication. PMID- 26352440 TI - Stability of Attitudes to the Ethical Issues Raised by the Return of Incidental Genomic Research Findings in Children: A Follow-Up Study. AB - OBJECTIVE: We explore the stability of parental attitudes to the ethical issues raised by the return of genomic research results. METHODS: A 19-item questionnaire was mailed to participants in a large genome research consortium 18 months following a baseline survey. We describe the stability of parental attitudes to (a) sharing of genomic research results, (b) endorsement of children in genomic research, (c) responsibilities of researchers, and (d) responsibilities to extended family. We also explore their experience in receiving results. RESULTS: Of 170 original participants, 154 (91%) responded. Most participants expressed positive rights to receive incidental genomic research findings (85%), including when ameliorative therapy was unknown (85%). Only 3% found it acceptable to delegate the decision to return results to an independent committee. Researchers, either with a parent (42%) or physician (17%), were felt to be responsible to convey research results to children when they reach adulthood. Most participants (74%) indicated that results should be shared with potentially affected extended family. These results are very similar to those of the baseline survey. All participants who received genomic results would do so again and reported actions similar to their expressed attitudes. CONCLUSIONS: The opinions of parents regarding genomic research remain stable over time. Guidelines on the return of results should incorporate these findings. PMID- 26352439 TI - 4-Hydroxyisoleucine improves insulin resistance in HepG2 cells by decreasing TNF alpha and regulating the expression of insulin signal transduction proteins. AB - Previous studies have indicated that 4-hydroxyisoleucine (4-HIL) improves insulin resistance, however, the underlying mechanisms remain to be elucidated. In the present study, the molecular mechanisms underlying how 4-HIL improves insulin resistance in hepatocytes were examined. HepG2 cells were co-cultured with insulin and a high glucose concentration to obtain insulin-resistant (IR) HepG2 cells. Insulin sensitivity was determined by measuring the glucose uptake rate. The IR HepG2 cells were treated with different concentrations of 4-HIL to determine its effect on IR Hep2 cells. The levels of tumor necrosis factor-alpha (TNF-alpha) were measured by an enzyme-linked immunosorbent assay and protein levels of TNF-alpha converting enzyme (TACE)/tissue inhibitor of metalloproteinase 3 (TIMP3), insulin receptor substrate (IRS)-1, IRS-2, phosphorylated (p)-IRS-1 (Ser307) and glucose transporter type 4 (GLUT4) were measured by western blot analysis. The results of the present study demonstrated that insulin-induced glucose uptake was reduced in IR HepG2 cells; however, this reduction was reversed by 4-HIL in a dose-dependent manner. 4-HIL achieved this effect by downregulating the expression of TNF-alpha and TACE, and upregulating the expression of TIMP3 in IR HepG2 cells. In addition, 4-HIL increased the expression of the insulin transduction regulators IRS-1 and GLUT4, and decreased the expression of p-IRS-1 (Ser307), without affecting the expression of IRS-2. The present study suggests that 4-HIL improved insulin resistance in HepG2 cells by the following mechanisms: 4-HIL reduced TNF-alpha levels by affecting the protein expression of the TACE/TIMP3 system and 4-HIL stimulated the expression of IRS-1 and GLUT4, but inhibited the expression of p-IRS-1 (Ser307). PMID- 26352441 TI - Phosphoryl transfer reaction catalyzed by membrane diacylglycerol kinase: a theoretical mechanism study. AB - Diacylglycerol kinase is an integral membrane protein which catalyzes phosphoryl transfer from ATP to diacylglycerol. As the smallest kinase known, it shares no sequence homology with conventional kinases and possesses a distinct trimer structure. Thus far, its catalytic mechanism remains elusive. Using molecular dynamics and quantum mechanics calculations, we investigated the co-factor and the substrate binding and phosphoryl transfer mechanism. Based on the analysis of density functional theory calculations, we reveal that the phosphorylation reaction of diacylglycerol kinase features the same phosphoryl transfer mechanism as other kinases, despite its unique structural properties. Our results further show that the active site is relatively open and able to accommodate ligands in multiple orientations, suggesting that the optimization of binding orientations and conformational changes would occur prior to actual phosphoryl transfer. PMID- 26352442 TI - Generalized Flows for Optimal Inference in Higher Order MRF-MAP. AB - Use of higher order clique potentials in MRF-MAP problems has been limited primarily because of the inefficiencies of the existing algorithmic schemes. We propose a new combinatorial algorithm for computing optimal solutions to 2 label MRF-MAP problems with higher order clique potentials. The algorithm runs in time O(2(k)n(3)) in the worst case (k is size of clique and n is the number of pixels). A special gadget is introduced to model flows in a higher order clique and a technique for building a flow graph is specified. Based on the primal dual structure of the optimization problem, the notions of the capacity of an edge and a cut are generalized to define a flow problem. We show that in this flow graph, when the clique potentials are submodular, the max flow is equal to the min cut, which also is the optimal solution to the problem. We show experimentally that our algorithm provides significantly better solutions in practice and is hundreds of times faster than solution schemes like Dual Decomposition [1], TRWS [2] and Reduction [3], [4], [5]. The framework represents a significant advance in handling higher order problems making optimal inference practical for medium sized cliques. PMID- 26352443 TI - Learning Weighted Lower Linear Envelope Potentials in Binary Markov Random Fields. AB - Markov random fields containing higher-order terms are becoming increasingly popular due to their ability to capture complicated relationships as soft constraints involving many output random variables. In computer vision an important class of constraints encode a preference for label consistency over large sets of pixels and can be modeled using higher-order terms known as lower linear envelope potentials. In this paper we develop an algorithm for learning the parameters of binary Markov random fields with weighted lower linear envelope potentials. We first show how to perform exact energy minimization on these models in time polynomial in the number of variables and number of linear envelope functions. Then, with tractable inference in hand, we show how the parameters of the lower linear envelope potentials can be estimated from labeled training data within a max-margin learning framework. We explore three variants of the lower linear envelope parameterization and demonstrate results on both synthetic and real-world problems. PMID- 26352444 TI - Submodular Relaxation for Inference in Markov Random Fields. AB - In this paper we address the problem of finding the most probable state of a discrete Markov random field (MRF), also known as the MRF energy minimization problem. The task is known to be NP-hard in general and its practical importance motivates numerous approximate algorithms. We propose a submodular relaxation approach (SMR) based on a Lagrangian relaxation of the initial problem. Unlike the dual decomposition approach of Komodakis et al. [29] SMR does not decompose the graph structure of the initial problem but constructs a submodular energy that is minimized within the Lagrangian relaxation. Our approach is applicable to both pairwise and high-order MRFs and allows to take into account global potentials of certain types. We study theoretical properties of the proposed approach and evaluate it experimentally. PMID- 26352445 TI - Context-Aware Activity Modeling Using Hierarchical Conditional Random Fields. AB - In this paper, rather than modeling activities in videos individually, we jointly model and recognize related activities in a scene using both motion and context features. This is motivated from the observations that activities related in space and time rarely occur independently and can serve as the context for each other. We propose a two-layer conditional random field model, that represents the action segments and activities in a hierarchical manner. The model allows the integration of both motion and various context features at different levels and automatically learns the statistics that capture the patterns of the features. With weakly labeled training data, the learning problem is formulated as a max margin problem and is solved by an iterative algorithm. Rather than generating activity labels for individual activities, our model simultaneously predicts an optimum structural label for the related activities in the scene. We show promising results on the UCLA Office Dataset and VIRAT Ground Dataset that demonstrate the benefit of hierarchical modeling of related activities using both motion and context features. PMID- 26352446 TI - Parameter Estimation and Energy Minimization for Region-Based Semantic Segmentation. AB - We consider the problem of parameter estimation and energy minimization for a region-based semantic segmentation model. The model divides the pixels of an image into non-overlapping connected regions, each of which is to a semantic class. In the context of energy minimization, the main problem we face is the large number of putative pixel-to-region assignments. We address this problem by designing an accurate linear programming based approach for selecting the best set of regions from a large dictionary. The dictionary is constructed by merging and intersecting segments obtained from multiple bottom-up over-segmentations. The linear program is solved efficiently using dual decomposition. In the context of parameter estimation, the main problem we face is the lack of fully supervised data. We address this issue by developing a principled framework for parameter estimation using diverse data. More precisely, we propose a latent structural support vector machine formulation, where the latent variables model any missing information in the human annotation. Of particular interest to us are three types of annotations: (i) images segmented using generic foreground or background classes; (ii) images with bounding boxes specified for objects; and (iii) images labeled to indicate the presence of a class. Using large, publicly available datasets we show that our methods are able to significantly improve the accuracy of the region-based model. PMID- 26352447 TI - A Hypergraph-Based Reduction for Higher-Order Binary Markov Random Fields. AB - Higher-order Markov Random Fields, which can capture important properties of natural images, have become increasingly important in computer vision. While graph cuts work well for first-order MRF's, until recently they have rarely been effective for higher-order MRF's. Ishikawa's graph cut technique [1], [2] shows great promise for many higher-order MRF's. His method transforms an arbitrary higher-order MRF with binary labels into a first-order one with the same minima. If all the terms are submodular the exact solution can be easily found; otherwise, pseudoboolean optimization techniques can produce an optimal labeling for a subset of the variables. We present a new transformation with better performance than [1], [2], both theoretically and experimentally. While [1], [2] transforms each higher-order term independently, we use the underlying hypergraph structure of the MRF to transform a group of terms at once. For n binary variables, each of which appears in terms with k other variables, at worst we produce n non-submodular terms, while [1], [2] produces O(nk). We identify a local completeness property under which our method perform even better, and show that under certain assumptions several important vision problems (including common variants of fusion moves) have this property. We show experimentally that our method produces smaller weight of non-submodular edges, and that this metric is directly related to the effectiveness of QPBO [3]. Running on the same field of experts dataset used in [1], [2] we optimally label significantly more variables (96 versus 80 percent) and converge more rapidly to a lower energy. Preliminary experiments suggest that some other higher-order MRF's used in stereo [4] and segmentation [5] are also locally complete and would thus benefit from our work. PMID- 26352448 TI - Accelerating Particle Filter Using Randomized Multiscale and Fast Multipole Type Methods. AB - Particle filter is a powerful tool for state tracking using non-linear observations. We present a multiscale based method that accelerates the tracking computation by particle filters. Unlike the conventional way, which calculates weights over all particles in each cycle of the algorithm, we sample a small subset from the source particles using matrix decomposition methods. Then, we apply a function extension algorithm that uses a particle subset to recover the density function for all the rest of the particles not included in the chosen subset. The computational effort is substantial especially when multiple objects are tracked concurrently. The proposed algorithm significantly reduces the computational load. By using the Fast Gaussian Transform, the complexity of the particle selection step is reduced to a linear time in n and k, where n is the number of particles and k is the number of particles in the selected subset. We demonstrate our method on both simulated and on real data such as object tracking in video sequences. PMID- 26352449 TI - Actions in the Eye: Dynamic Gaze Datasets and Learnt Saliency Models for Visual Recognition. AB - Systems based on bag-of-words models from image features collected at maxima of sparse interest point operators have been used successfully for both computer visual object and action recognition tasks. While the sparse, interest-point based approach to recognition is not inconsistent with visual processing in biological systems that operate in 'saccade and fixate' regimes, the methodology and emphasis in the human and the computer vision communities remains sharply distinct. Here, we make three contributions aiming to bridge this gap. First, we complement existing state-of-the art large scale dynamic computer vision annotated datasets like Hollywood-2 [1] and UCF Sports [2] with human eye movements collected under the ecological constraints of visual action and scene context recognition tasks. To our knowledge these are the first large human eye tracking datasets to be collected and made publicly available for video, vision.imar.ro/eyetracking (497,107 frames, each viewed by 19 subjects), unique in terms of their (a) large scale and computer vision relevance, (b) dynamic, video stimuli, (c) task control, as well as free-viewing. Second, we introduce novel dynamic consistency and alignment measures, which underline the remarkable stability of patterns of visual search among subjects. Third, we leverage the significant amount of collected data in order to pursue studies and build automatic, end-to-end trainable computer vision systems based on human eye movements. Our studies not only shed light on the differences between computer vision spatio-temporal interest point image sampling strategies and the human fixations, as well as their impact for visual recognition performance, but also demonstrate that human fixations can be accurately predicted, and when used in an end-to-end automatic system, leveraging some of the advanced computer vision practice, can lead to state of the art results. PMID- 26352450 TI - A Framework for Efficient Structured Max-Margin Learning of High-Order MRF Models. AB - We present a very general algorithm for structured prediction learning that is able to efficiently handle discrete MRFs/CRFs (including both pairwise and higher order models) so long as they can admit a decomposition into tractable subproblems. At its core, it relies on a dual decomposition principle that has been recently employed in the task of MRF optimization. By properly combining such an approach with a max-margin learning method, the proposed framework manages to reduce the training of a complex high-order MRF to the parallel training of a series of simple slave MRFs that are much easier to handle. This leads to a very efficient and general learning scheme that relies on solid mathematical principles. We thoroughly analyze its theoretical properties, and also show that it can yield learning algorithms of increasing accuracy since it naturally allows a hierarchy of convex relaxations to be used for loss-augmented MAP-MRF inference within a max-margin learning approach. Furthermore, it can be easily adapted to take advantage of the special structure that may be present in a given class of MRFs. We demonstrate the generality and flexibility of our approach by testing it on a variety of scenarios, including training of pairwise and higher-order MRFs, training by using different types of regularizers and/or different types of dissimilarity loss functions, as well as by learning of appropriate models for a variety of vision tasks (including high-order models for compact pose-invariant shape priors, knowledge-based segmentation, image denoising, stereo matching as well as high-order Potts MRFs). PMID- 26352451 TI - Learning the Information Divergence. AB - Information divergence that measures the difference between two nonnegative matrices or tensors has found its use in a variety of machine learning problems. Examples are Nonnegative Matrix/Tensor Factorization, Stochastic Neighbor Embedding, topic models, and Bayesian network optimization. The success of such a learning task depends heavily on a suitable divergence. A large variety of divergences have been suggested and analyzed, but very few results are available for an objective choice of the optimal divergence for a given task. Here we present a framework that facilitates automatic selection of the best divergence among a given family, based on standard maximum likelihood estimation. We first propose an approximated Tweedie distribution for the beta-divergence family. Selecting the best beta then becomes a machine learning problem solved by maximum likelihood. Next, we reformulate alpha-divergence in terms of beta-divergence, which enables automatic selection of alpha by maximum likelihood with reuse of the learning principle for beta-divergence. Furthermore, we show the connections between gamma- and beta-divergences as well as Renyi- and alpha-divergences, such that our automatic selection framework is extended to non-separable divergences. Experiments on both synthetic and real-world data demonstrate that our method can quite accurately select information divergence across different learning problems and various divergence families. PMID- 26352452 TI - Marginal Consistency: Upper-Bounding Partition Functions over Commutative Semirings. AB - Many inference tasks in pattern recognition and artificial intelligence lead to partition functions in which addition and multiplication are abstract binary operations forming a commutative semiring. By generalizing max-sum diffusion (one of convergent message passing algorithms for approximate MAP inference in graphical models), we propose an iterative algorithm to upper bound such partition functions over commutative semirings. The iteration of the algorithm is remarkably simple: change any two factors of the partition function such that their product remains the same and their overlapping marginals become equal. In many commutative semirings, repeating this iteration for different pairs of factors converges to a fixed point when the overlapping marginals of every pair of factors coincide. We call this state marginal consistency. During that, an upper bound on the partition function monotonically decreases. This abstract algorithm unifies several existing algorithms, including max-sum diffusion and basic constraint propagation (or local consistency) algorithms in constraint programming. We further construct a hierarchy of marginal consistencies of increasingly higher levels and show than any such level can be enforced by adding identity factors of higher arity (order). Finally, we discuss instances of the framework for several semirings, including the distributive lattice and the max sum and sum-product semirings. PMID- 26352453 TI - Mixture of Subspaces Image Representation and Compact Coding for Large-Scale Image Retrieval. AB - There are two major approaches to content-based image retrieval using local image descriptors. One is descriptor-by-descriptor matching and the other is based on comparison of global image representation that describes the set of local descriptors of each image. In large-scale problems, the latter is preferred due to its smaller memory requirements; however, it tends to be inferior to the former in terms of retrieval accuracy. To achieve both low memory cost and high accuracy, we investigate an asymmetric approach in which the probability distribution of local descriptors is modeled for each individual database image while the local descriptors of a query are used as is. We adopt a mixture model of probabilistic principal component analysis. The model parameters constitute a global image representation to be stored in database. Then the likelihood function is employed to compute a matching score between each database image and a query. We also propose an algorithm to encode our image representation into more compact codes. Experimental results demonstrate that our method can represent each database image in less than several hundred bytes achieving higher retrieval accuracy than the state-of-the-art method using Fisher vectors. PMID- 26352454 TI - Text Detection and Recognition in Imagery: A Survey. AB - This paper analyzes, compares, and contrasts technical challenges, methods, and the performance of text detection and recognition research in color imagery. It summarizes the fundamental problems and enumerates factors that should be considered when addressing these problems. Existing techniques are categorized as either stepwise or integrated and sub-problems are highlighted including text localization, verification, segmentation and recognition. Special issues associated with the enhancement of degraded text and the processing of video text, multi-oriented, perspectively distorted and multilingual text are also addressed. The categories and sub-categories of text are illustrated, benchmark datasets are enumerated, and the performance of the most representative approaches is compared. This review provides a fundamental comparison and analysis of the remaining problems in the field. PMID- 26352455 TI - Time-of-Flight Sensor Calibration for a Color and Depth Camera Pair. AB - We present a calibration method of a time-of-flight (ToF) sensor and a color camera pair to align the 3D measurements with the color image correctly. We have designed a 2.5D pattern board with irregularly placed holes to be accurately detected from low resolution depth images of a ToF camera as well as from high resolution color images. In order to improve the accuracy of the 3D measurements of a ToF camera, we propose to perform ray correction and range bias correction. We reset the transformation of the ToF sensor which transforms the radial distance into the scene depth in Cartesian coordinate through ray correction. Then we capture a planar scene from different depths to correct the distance error that is shown to be dependent not only on the distance but also on the pixel location. The range error profiles along the calibrated distance are classified according to their wiggling shapes and each cluster of profiles with similar shape are separately estimated using a B-spline function. The standard deviation of the remaining random noise is recorded as an uncertainty information of distance measurements. We show the performance of our calibration method quantitatively and qualitatively on various datasets, and validate the impact of our method by demonstrating an RGB-D shape refinement application. PMID- 26352456 TI - GPstruct: Bayesian Structured Prediction Using Gaussian Processes. AB - We introduce a conceptually novel structured prediction model, GPstruct, which is kernelized, non-parametric and Bayesian, by design. We motivate the model with respect to existing approaches, among others, conditional random fields (CRFs), maximum margin Markov networks (M3N), and structured support vector machines (SVMstruct), which embody only a subset of its properties. We present an inference procedure based on Markov Chain Monte Carlo. The framework can be instantiated for a wide range of structured objects such as linear chains, trees, grids, and other general graphs. As a proof of concept, the model is benchmarked on several natural language processing tasks and a video gesture segmentation task involving a linear chain structure. We show prediction accuracies for GPstruct which are comparable to or exceeding those of CRFs and SVMstruct. PMID- 26352457 TI - On Reducing the Effect of Covariate Factors in Gait Recognition: A Classifier Ensemble Method. AB - Robust human gait recognition is challenging because of the presence of covariate factors such as carrying condition, clothing, walking surface, etc. In this paper, we model the effect of covariates as an unknown partial feature corruption problem. Since the locations of corruptions may differ for different query gaits, relevant features may become irrelevant when walking condition changes. In this case, it is difficult to train one fixed classifier that is robust to a large number of different covariates. To tackle this problem, we propose a classifier ensemble method based on the random subspace Method (RSM) and majority voting (MV). Its theoretical basis suggests it is insensitive to locations of corrupted features, and thus can generalize well to a large number of covariates. We also extend this method by proposing two strategies, i.e, local enhancing (LE) and hybrid decision-level fusion (HDF) to suppress the ratio of false votes to true votes (before MV). The performance of our approach is competitive against the most challenging covariates like clothing, walking surface, and elapsed time. We evaluate our method on the USF dataset and OU-ISIR-B dataset, and it has much higher performance than other state-of-the-art algorithms. PMID- 26352458 TI - Neutral thioether and selenoether macrocyclic coordination to Group 1 cations (Li Cs) - synthesis, spectroscopic and structural properties. AB - The complexes [M(L)][BAr(F)] (BAr(F) = tetrakis{3,5-bis(trifluoromethyl) phenyl}borate), L = [18]aneO4S2 (1,4,10,13-tetraoxa-7,16-dithiacyclooctadecane): M = Li-Cs; L = [18]aneO2S4 (1,10-dioxa-4,7,13,16-tetrathiacyclooctadecane): M = Li, Na, K; L = [18]aneO4Se2 (1,4,10,13-tetraoxa-7,16-diselenacyclooctadecane): M = Na, K, as well as [Na(18-crown-6)][BAr(F)], are obtained in good yield as crystalline solids by reaction of M[BAr(F)] with the appropriate macrocycle in dry CH2Cl2. X-ray crystallographic analyses of [Li([18]aneO4S2)][BAr(F)] and [Li([18]aneO2S4)][BAr(F)] show discrete distorted octahedral cations with hexadentate coordination to the macrocycle. The heavier alkali metal complexes all contain hexadentate coordination of the heterocrown, supplemented by MF interactions via the anions, producing extended structures with higher coordination numbers; Na: CN = 7 or 8; K: CN = 8; Rb: CN = 9; Cs: CN = 8 or 10. Notably, all of the structures exhibit significant M-S/Se coordination. The crystal structures of the potassium and rubidium complexes show two distinct [M(heterocrown)](+) cations, one with MF interactions to two mutually cis [BAr(F)](-) anions, and the other with mutually trans [BAr(F)](-) anions, giving 1D chain polymers. Solution multinuclear ((1)H, (13)C, (7)Li, (23)Na, (133)Cs) NMR data show that the macrocyclic coordination is retained in CH2Cl2 solution. PMID- 26352459 TI - QbD-oriented development and validation of a bioanalytical method for nevirapine with enhanced liquid-liquid extraction and chromatographic separation. AB - The present studies describe the systematic quality by design (QbD)-oriented development and validation of a simple, rapid, sensitive and cost-effective reversed-phase HPLC bioanalytical method for nevirapine in rat plasma. Chromatographic separation was carried out on a C18 column using isocratic 68:9:23% v/v elution of methanol, acetonitrile and water (pH 3, adjusted by orthophosphoric acid) at a flow rate of 1.0 mL/min using UV detection at 230 nm. A Box-Behnken design was applied for chromatographic method optimization taking mobile phase ratio, pH and flow rate as the critical method parameters (CMPs) from screening studies. Peak area, retention time, theoretical plates and peak tailing were measured as the critical analytical attributes (CAAs). Further, the bioanalytical liquid-liquid extraction process was optimized using an optimal design by selecting extraction time, centrifugation speed and temperature as the CMPs for percentage recovery of nevirapine as the CAA. The search for an optimum chromatographic solution was conducted through numerical desirability function. Validation studies performed as per the US Food and Drug Administration requirements revealed results within the acceptance limit. In a nutshell, the studies successfully demonstrate the utility of analytical QbD approach for the rational development of a bioanalytical method with enhanced chromatographic separation and recovery of nevirapine in rat plasma. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26352460 TI - An early post-traumatic reaction of lymph-heart striated muscle fibers in adult frog Rana temporaria during the first postoperative week: An electron microscopic and autoradiographic study. AB - According to the current opinion, lymph-heart striated muscle represents a specialized type of skeletal muscles in frogs. Here, we studied muscle fibers in mechanically damaged lymph hearts during the first postoperative week using electron-microscopic autoradiography. We present evidence that both, the satellite cells and pre-existing muscle fibers bordering the site of injury, contribute directly to the lymph-heart muscle regeneration. Several muscle fibers located in the vicinity of the damaged area displayed features of nuclear and sarcoplasmic activation. We also observed ultrastructural changes indicating activation of a few satellite cells, namely decondensation of chromatin, enlargement of nuclei and nucleoli, appearance of free ribosomes and rough endoplasmic reticulum tubules in the cytoplasm. Electron-microscopic autoradiography showed that 4 h after single (3)H-thymidine administration on the seventh day after injury not only the activated satellite cells, but also some nuclei of myofibers bordering the injured zone are labeled. We showed that both, the myonuclei of fibers displaying the signs of degenerative/reparative processes in the sarcoplasm and the myonuclei of the fibers enriched with highly organized myofibrils, can re-enter into the S-phase. Our results indicate that the nuclei of lymph-heart myofibers can reactivate DNA synthesis during regenerative myogenesis, unlike the situation in regenerating frog skeletal muscle where myogenic cells do not synthesize DNA at the onset of myofibrillogenesis. PMID- 26352461 TI - Variation in trait trade-offs allows differentiation among predefined plant functional types: implications for predictive ecology. AB - Plant functional types (PFTs) aggregate the variety of plant species into a small number of functionally different classes. We examined to what extent plant traits, which reflect species' functional adaptations, can capture functional differences between predefined PFTs and which traits optimally describe these differences. We applied Gaussian kernel density estimation to determine probability density functions for individual PFTs in an n-dimensional trait space and compared predicted PFTs with observed PFTs. All possible combinations of 1-6 traits from a database with 18 different traits (total of 18 287 species) were tested. A variety of trait sets had approximately similar performance, and 4-5 traits were sufficient to classify up to 85% of the species into PFTs correctly, whereas this was 80% for a bioclimatically defined tree PFT classification. Well performing trait sets included combinations of correlated traits that are considered functionally redundant within a single plant strategy. This analysis quantitatively demonstrates how structural differences between PFTs are reflected in functional differences described by particular traits. Differentiation between PFTs is possible despite large overlap in plant strategies and traits, showing that PFTs are differently positioned in multidimensional trait space. This study therefore provides the foundation for important applications for predictive ecology. PMID- 26352462 TI - Optimization of tissue physical parameters for accurate temperature estimation from finite-element simulation of radiofrequency ablation. AB - Computational finite element models are commonly used for the simulation of radiofrequency ablation (RFA) treatments. However, the accuracy of these simulations is limited by the lack of precise knowledge of tissue parameters. In this technical note, an inverse solver based on the unscented Kalman filter (UKF) is proposed to optimize values for specific heat, thermal conductivity, and electrical conductivity resulting in accurately simulated temperature elevations. A total of 15 RFA treatments were performed on ex vivo bovine liver tissue. For each RFA treatment, 15 finite-element simulations were performed using a set of deterministically chosen tissue parameters to estimate the mean and variance of the resulting tissue ablation. The UKF was implemented as an inverse solver to recover the specific heat, thermal conductivity, and electrical conductivity corresponding to the measured area of the ablated tissue region, as determined from gross tissue histology. These tissue parameters were then employed in the finite element model to simulate the position- and time-dependent tissue temperature. Results show good agreement between simulated and measured temperature. PMID- 26352463 TI - A Novel Ferrocenyl Naphthoquinone Fused Crown Ether as a Multisensor for Water Determination in Acetonitrile and Selective Cation Binding. AB - A multisensor which is based on a novel multifunctional triad molecule, ferrocenyl naphthoquinone fused crown ether (Fc-cnq) bearing ferrocene, quinone, and crown ether functional groups together, was synthesized and characterized in this study. Sensing performance of a trace amount of water and the selective cation binding capabilities of this multisensor were carried out by the electrochemical, spectroelectrochemical, and spectrophotometric titration techniques in acetonitrile (CH3CN). It was shown that the potential separation (E((Fc))1/2 - E((2))1/2) between the second reduction of naphthoquinone and the oxidation processes of ferrocene in the triad molecule Fc-cnq was proportional to the amount of water due to the hydrogen-bonding interactions between water and the doubly reduced species (Fc-cnq(2-)). This property enabled Fc-cnq to detect the trace amount of water in CH3CN. The half-wave potential (E((Fc))1/2) of the ferrocene in Fc-cnq was used as an internal reference potential, and it defined the accuracy of the detection. In addition, by using the UV-vis spectrophotometric titration technique in CH3CN, it was also shown that the Fc cnq multisensor could bind Ba(2+) and Ca(2+) cations selectively. We proposed that the intramolecular charge-transfer (CT) transition which occurred between the donor ferrocene and the acceptor naphthoquinone was the principle mechanism for the selective binding property of this multisensor. Quantum chemical calculations were also performed to investigate optical and electronic properties of the Fc-cnq molecule. PMID- 26352465 TI - Design of Highly Stable Iminophosphoranes as Recyclable Organocatalysts: Application to Asymmetric Chlorinations of Oxindoles. AB - A new family of tartaric acid derived chiral iminophosphoranes has been developed as highly effective organocatalysts in the asymmetric chlorinations of 3 substituted oxindoles with a high level of enantioselectivity. Importantly, these catalysts are air- and moisture-stable. Recovery of the catalyst after simple chromatographic separation for reuse in the model reaction was achieved; the catalyst can be recycled six times without loss of any enantioselectivity. Several advantages of this catalytic process are high conversion after a very short reaction time at ambient temperature, low catalytic loading, and scale-up to multigram quantities with an excellent enantiomeric excess value of >99%, which meets the enantiomeric purity required for pharmaceutical purposes. PMID- 26352464 TI - Effect of Detergents on Galactoside Binding by Melibiose Permeases. AB - The effect of various detergents on the stability and function of the melibiose permeases of Escherichia coli (MelBEc) and Salmonella typhimurium (MelBSt) was studied. In n-dodecyl-beta-d-maltoside (DDM) or n-undecyl-beta-d-maltoside (UDM), WT MelBSt binds melibiose with an affinity similar to that in the membrane. However, with WT MelBEc or MelBSt mutants (Arg141 -> Cys, Arg295 -> Cys, or Arg363 -> Cys), galactoside binding is not detected in these detergents, but binding to the phosphotransferase protein IIA(Glc) is maintained. In the amphiphiles lauryl maltose neopentyl glycol (MNG-3) or glyco-diosgenin (GDN), galactoside binding with all of the MelB proteins is observed, with slightly reduced affinities. MelBSt is more thermostable than MelBEc, and the thermostability of either MelB is largely increased in MNG-3 or GDN. Therefore, the functional defect with DDM or UDM likely results from the relative instability of the sensitive MelB proteins, and stability, as well as galactoside binding, is retained in MNG-3 or GDN. Furthermore, isothermal titration calorimetry of melibiose binding with MelBSt shows that the favorable entropic contribution to the binding free energy is decreased in MNG-3, indicating that the conformational dynamics of MelB is restricted in this detergent. PMID- 26352466 TI - Chemoenzymatic Assembly of Bacterial Glycoconjugates for Site-Specific Orthogonal Labeling. AB - The cell surfaces of bacteria are replete with diverse glycoconjugates that play pivotal roles in determining how bacteria interact with the environment and the hosts that they colonize. Studies to advance our understanding of these interactions rely on the availability of chemically defined glycoconjugates that can be selectively modified under orthogonal reaction conditions to serve as discrete ligands to probe biological interactions, in displayed arrays and as imaging agents. Herein, enzymes in the N-linked protein glycosylation (Pgl) pathway of Campylobacter jejuni are evaluated for their tolerance for azide modified UDP-sugar substrates, including derivatives of 2,4 diacetamidobacillosamine and N-acetylgalactosamine. In vitro analyses reveal that chemoenzymatic approaches are useful for the preparation of undecaprenol diphosphate-linked glycans and glycopeptides with site-specific introduction of azide functionality for orthogonal labeling at three specific sites in the heptasaccharide glycan. The uniquely modified glycoconjugates represent valuable tools for investigating the roles of C. jejuni cell surface glycoconjugates in host pathogen interactions. PMID- 26352467 TI - Unique Cutaneous Reaction to Second- and Third-Generation Tyrosine Kinase Inhibitors for Chronic Myeloid Leukemia. AB - BACKGROUND: Recently developed tyrosine kinase inhibitors (TKIs) offer first-line alternatives to patients with chronic myeloid leukemia. While these medications are generally well tolerated, cutaneous reactions occur frequently and can present a management challenge. We describe a newly recognized skin reaction to dasatinib and nilotinib and extend it to the newer agent ponatinib. OBSERVATIONS: Nine patients developed varying degrees of a clinically and histopathologically lichenoid exanthem comprised of erythematous, predominately follicular papules with scale and alopecia. The pattern is reminiscent of the scarring and nonscarring alopecia of follicular lichen planus/lichen planopilaris (LPP) with keratosis pilaris-like LPP--the rare Graham-Little-Piccardi-Lassueur syndrome. Importantly, the accompanying pruritus can be severe enough to result in discontinuation of therapy. CONCLUSIONS: Clinicians should be aware of this unusual eruption to the newer TKIs and the potential therapeutic challenges. Understanding these eruptions may also suggest potential mechanisms in the idiopathic forms of follicular lichen planus. PMID- 26352469 TI - Inequality and visibility of wealth in experimental social networks. AB - Humans prefer relatively equal distributions of resources, yet societies have varying degrees of economic inequality. To investigate some of the possible determinants and consequences of inequality, here we perform experiments involving a networked public goods game in which subjects interact and gain or lose wealth. Subjects (n = 1,462) were randomly assigned to have higher or lower initial endowments, and were embedded within social networks with three levels of economic inequality (Gini coefficient = 0.0, 0.2, and 0.4). In addition, we manipulated the visibility of the wealth of network neighbours. We show that wealth visibility facilitates the downstream consequences of initial inequality in initially more unequal situations, wealth visibility leads to greater inequality than when wealth is invisible. This result reflects a heterogeneous response to visibility in richer versus poorer subjects. We also find that making wealth visible has adverse welfare consequences, yielding lower levels of overall cooperation, inter-connectedness, and wealth. High initial levels of economic inequality alone, however, have relatively few deleterious welfare effects. PMID- 26352468 TI - Development of a selective left-hemispheric fronto-temporal network for processing syntactic complexity in language comprehension. AB - The development of language comprehension abilities in childhood is closely related to the maturation of the brain, especially the ability to process syntactically complex sentences. Recent studies proposed that the fronto-temporal connection within left perisylvian regions, supporting the processing of syntactically complex sentences, is still immature at preschool age. In the current study, resting state functional magnetic resonance imaging data were acquired from typically developing 5-year-old children and adults to shed further light on the brain functional development. Children additionally performed a behavioral syntactic comprehension test outside the scanner. The amplitude of low frequency fluctuations was analyzed in order to identify the functional correlation networks of language-relevant brain regions. Results showed an intrahemispheric correlation between left inferior frontal gyrus (IFG) and left posterior superior temporal sulcus (pSTS) in adults, whereas an interhemispheric correlation between left IFG and its right-hemispheric homolog was predominant in children. Correlation analysis between resting-state functional connectivity and sentence processing performance in 5-year-olds revealed that local connectivity within the left IFG is associated with competence of processing syntactically simple canonical sentences, while long-range connectivity between IFG and pSTS in left hemisphere is associated with competence of processing syntactically relatively more complex non-canonical sentences. The present developmental data suggest that a selective left fronto-temporal connectivity network for processing complex syntax is already in functional connection at the age of 5 years when measured in a non-task situation. The correlational findings provide new insight into the relationship between intrinsic functional connectivity and syntactic language abilities in preschool children. PMID- 26352470 TI - Parkinson's disease: Crystals of a toxic core. PMID- 26352471 TI - Labelling and optical erasure of synaptic memory traces in the motor cortex. AB - Dendritic spines are the major loci of synaptic plasticity and are considered as possible structural correlates of memory. Nonetheless, systematic manipulation of specific subsets of spines in the cortex has been unattainable, and thus, the link between spines and memory has been correlational. We developed a novel synaptic optoprobe, AS-PaRac1 (activated synapse targeting photoactivatable Rac1), that can label recently potentiated spines specifically, and induce the selective shrinkage of AS-PaRac1-containing spines. In vivo imaging of AS-PaRac1 revealed that a motor learning task induced substantial synaptic remodelling in a small subset of neurons. The acquired motor learning was disrupted by the optical shrinkage of the potentiated spines, whereas it was not affected by the identical manipulation of spines evoked by a distinct motor task in the same cortical region. Taken together, our results demonstrate that a newly acquired motor skill depends on the formation of a task-specific dense synaptic ensemble. PMID- 26352472 TI - Epigenetics: The karma of oil palms. PMID- 26352474 TI - Neuroscience: Forgetfulness illuminated. PMID- 26352473 TI - Structure of the toxic core of alpha-synuclein from invisible crystals. AB - The protein alpha-synuclein is the main component of Lewy bodies, the neuron associated aggregates seen in Parkinson disease and other neurodegenerative pathologies. An 11-residue segment, which we term NACore, appears to be responsible for amyloid formation and cytotoxicity of human alpha-synuclein. Here we describe crystals of NACore that have dimensions smaller than the wavelength of visible light and thus are invisible by optical microscopy. As the crystals are thousands of times too small for structure determination by synchrotron X-ray diffraction, we use micro-electron diffraction to determine the structure at atomic resolution. The 1.4 A resolution structure demonstrates that this method can determine previously unknown protein structures and here yields, to our knowledge, the highest resolution achieved by any cryo-electron microscopy method to date. The structure exhibits protofibrils built of pairs of face-to-face beta sheets. X-ray fibre diffraction patterns show the similarity of NACore to toxic fibrils of full-length alpha-synuclein. The NACore structure, together with that of a second segment, inspires a model for most of the ordered portion of the toxic, full-length alpha-synuclein fibril, presenting opportunities for the design of inhibitors of alpha-synuclein fibrils. PMID- 26352476 TI - Spawning rings of exceptional points out of Dirac cones. AB - The Dirac cone underlies many unique electronic properties of graphene and topological insulators, and its band structure--two conical bands touching at a single point--has also been realized for photons in waveguide arrays, atoms in optical lattices, and through accidental degeneracy. Deformation of the Dirac cone often reveals intriguing properties; an example is the quantum Hall effect, where a constant magnetic field breaks the Dirac cone into isolated Landau levels. A seemingly unrelated phenomenon is the exceptional point, also known as the parity-time symmetry breaking point, where two resonances coincide in both their positions and widths. Exceptional points lead to counter-intuitive phenomena such as loss-induced transparency, unidirectional transmission or reflection, and lasers with reversed pump dependence or single-mode operation. Dirac cones and exceptional points are connected: it was theoretically suggested that certain non-Hermitian perturbations can deform a Dirac cone and spawn a ring of exceptional points. Here we experimentally demonstrate such an 'exceptional ring' in a photonic crystal slab. Angle-resolved reflection measurements of the photonic crystal slab reveal that the peaks of reflectivity follow the conical band structure of a Dirac cone resulting from accidental degeneracy, whereas the complex eigenvalues of the system are deformed into a two-dimensional flat band enclosed by an exceptional ring. This deformation arises from the dissimilar radiation rates of dipole and quadrupole resonances, which play a role analogous to the loss and gain in parity-time symmetric systems. Our results indicate that the radiation existing in any open system can fundamentally alter its physical properties in ways previously expected only in the presence of material loss and gain. PMID- 26352475 TI - Loss of Karma transposon methylation underlies the mantled somaclonal variant of oil palm. AB - Somaclonal variation arises in plants and animals when differentiated somatic cells are induced into a pluripotent state, but the resulting clones differ from each other and from their parents. In agriculture, somaclonal variation has hindered the micropropagation of elite hybrids and genetically modified crops, but the mechanism responsible remains unknown. The oil palm fruit 'mantled' abnormality is a somaclonal variant arising from tissue culture that drastically reduces yield, and has largely halted efforts to clone elite hybrids for oil production. Widely regarded as an epigenetic phenomenon, 'mantling' has defied explanation, but here we identify the MANTLED locus using epigenome-wide association studies of the African oil palm Elaeis guineensis. DNA hypomethylation of a LINE retrotransposon related to rice Karma, in the intron of the homeotic gene DEFICIENS, is common to all mantled clones and is associated with alternative splicing and premature termination. Dense methylation near the Karma splice site (termed the Good Karma epiallele) predicts normal fruit set, whereas hypomethylation (the Bad Karma epiallele) predicts homeotic transformation, parthenocarpy and marked loss of yield. Loss of Karma methylation and of small RNA in tissue culture contributes to the origin of mantled, while restoration in spontaneous revertants accounts for non-Mendelian inheritance. The ability to predict and cull mantling at the plantlet stage will facilitate the introduction of higher performing clones and optimize environmentally sensitive land resources. PMID- 26352478 TI - "Surgery is simple-it requires only anatomy and hemostasis". PMID- 26352477 TI - A new cyanogenic metabolite in Arabidopsis required for inducible pathogen defence. AB - Thousands of putative biosynthetic genes in Arabidopsis thaliana have no known function, which suggests that there are numerous molecules contributing to plant fitness that have not yet been discovered. Prime among these uncharacterized genes are cytochromes P450 upregulated in response to pathogens. Here we start with a single pathogen-induced P450 (ref. 5), CYP82C2, and use a combination of untargeted metabolomics and coexpression analysis to uncover the complete biosynthetic pathway to 4-hydroxyindole-3-carbonyl nitrile (4-OH-ICN), a previously unknown Arabidopsis metabolite. This metabolite harbours cyanogenic functionality that is unprecedented in plants and exceedingly rare in nature; furthermore, the aryl cyanohydrin intermediate in the 4-OH-ICN pathway reveals a latent capacity for cyanogenic glucoside biosynthesis in Arabidopsis. By expressing 4-OH-ICN biosynthetic enzymes in Saccharomyces cerevisiae and Nicotiana benthamiana, we reconstitute the complete pathway in vitro and in vivo and validate the functions of its enzymes. Arabidopsis 4-OH-ICN pathway mutants show increased susceptibility to the bacterial pathogen Pseudomonas syringae, consistent with a role in inducible pathogen defence. Arabidopsis has been the pre-eminent model system for studying the role of small molecules in plant innate immunity; our results uncover a new branch of indole metabolism distinct from the canonical camalexin pathway, and support a role for this pathway in the Arabidopsis defence response. These results establish a more complete framework for understanding how the model plant Arabidopsis uses small molecules in pathogen defence. PMID- 26352480 TI - Ethinyl estradiol and levonorgestrel alter cognition and anxiety in rats concurrent with a decrease in tyrosine hydroxylase expression in the locus coeruleus and brain-derived neurotrophic factor expression in the hippocampus. AB - In the United States, more than ten million women use contraceptive hormones. Ethinyl estradiol and levonorgestrel have been mainstay contraceptive hormones for the last four decades. Surprisingly, there is scant information regarding their action on the central nervous system and behavior. Intact female rats received three weeks of subcutaneous ethinyl estradiol (10 or 30MUg/rat/day), levonorgestrel (20 or 60MUg/rat/day), a combination of both (10/20MUg/rat/day and 30/60MUg/rat/day), or vehicle. Subsequently, the rats were tested in three versions of the novel object recognition test to assess learning and memory, and a battery of tests for anxiety-like behavior. Serum estradiol and ovarian weights were measured. All treatment groups exhibited low endogenous 17beta-estradiol levels at the time of testing. Dose-dependent effects of drug treatment manifested in both cognitive and anxiety tests. All low dose drugs decreased anxiety-like behavior and impaired performance on novel object recognition. In contrast, the high dose ethinyl estradiol increased anxiety-like behavior and improved performance in cognitive testing. In the cell molecular analyses, low doses of all drugs induced a decrease in tyrosine hydroxylase mRNA and protein in the locus coeruleus. At the same time, low doses of ethinyl estradiol and ethinyl estradiol/levonorgestrel increased galanin protein in this structure. Consistent with the findings above, the low dose treatments of ethinyl estradiol and combination ethinyl estradiol/levonorgestrel reduced brain-derived neurotrophic factor mRNA in the hippocampus. These effects of ethinyl estradiol 10MUg alone and in combination with levonorgestrel 20MUg suggest a diminution of norepinephrine input into the hippocampus resulting in a decline in learning and memory. PMID- 26352482 TI - Development of the cortisol circadian rhythm in the light of stress early in life. AB - The secretion of the stress hormone cortisol follows a diurnal circadian rhythm. There are indications that this rhythm is affected by stress early in life. This paper addresses the development of the cortisol circadian rhythm between 1 and 6 years of age, and the role of maternal stress and anxiety early in the child's life on this (developing) rhythm. Participants were 193 healthy mother-child dyads from a community sample. Self-reported maternal stress and anxiety and physiological stress (saliva cortisol), were assessed prenatally (gestational week 37). Postnatally, self-reported maternal stress and anxiety were measured at 3, 6, 12, 30, and 72 months. Saliva cortisol samples from the children were collected on two days (four times each day) at 12, 30, and 72 months of age. The total amount of cortisol during the day and the cortisol decline over the day were determined to indicate children's cortisol circadian rhythm. Multilevel analyses showed that the total amount of cortisol decreased between 1 and 6 years. Furthermore, more maternal pregnancy-specific stress was related to higher total amounts of cortisol in the child. Higher levels of early postnatal maternal anxiety were associated with flatter cortisol declines in children. Higher levels of early postnatal maternal daily hassles were associated with steeper child cortisol declines over the day. These results indicated developmental change in children's cortisol secretion from 1 to 6 years and associations between maternal stress and anxiety early in children's lives and children's cortisol circadian rhythm in early childhood. PMID- 26352483 TI - Skin self-examination for concerning pigmented lesions appears to be consistent with dermatologist examination. PMID- 26352481 TI - Developmental histories of perceived racial discrimination and diurnal cortisol profiles in adulthood: A 20-year prospective study. AB - Perceived racial discrimination (PRD) has been associated with altered diurnal cortisol rhythms in past cross-sectional research. We investigate whether developmental histories of PRD, assessed prospectively, are associated with adult diurnal cortisol profiles. One-hundred and twelve (N=50 Black, N=62 White) adults from the Maryland Adolescent Development in Context Study provided saliva samples in adulthood (at approximately age 32 years) at waking, 30min after waking, and at bedtime for 7 days. Diurnal cortisol measures were calculated, including waking cortisol levels, diurnal cortisol slopes, the cortisol awakening response (CAR), and average daily cortisol (AUC). These cortisol outcomes were predicted from measures of PRD obtained over a 20-year period beginning when individuals were in 7th grade (approximately age 12). Greater average PRD measured across the 20-year period predicted flatter adult diurnal cortisol slopes for both Black and White adults, and a lower CAR. Greater average PRD also predicted lower waking cortisol for Black, but not White adults. PRD experiences in adolescence accounted for many of these effects. When adolescent and young adult PRD are entered together predicting cortisol outcomes, PRD experiences in adolescence (but not young adulthood) significantly predicted flatter diurnal cortisol slopes for both Black and White adults. Adolescent, but not young adult PRD, also significantly predicted lower waking and lower average cortisol for Black adults. Young adult PRD was, however, a stronger predictor of the CAR, predicting a marginally lower CAR for Whites, and a significantly larger CAR for Blacks. Effects were robust to controlling for covariates including health behaviors, depression, income and parent education levels. PRD experiences interacted with parent education and income to predict aspects of the diurnal cortisol rhythm. Although these results suggest PRD influences on cortisol for both Blacks and Whites, the key findings suggest that the effects are more pervasive for Blacks, affecting multiple aspects of the cortisol diurnal rhythm. In addition, adolescence is a more sensitive developmental period than adulthood for the impacts of PRD on adult stress biology. PMID- 26352484 TI - Diversity of Trypanosomatids in Cockroaches and the Description of Herpetomonas tarakana sp. n. AB - In this study, we surveyed six species of cockroaches, two synanthropic (i.e. ecologically associated with humans) and four wild, for intestinal trypanosomatid infections. Only the wild cockroach species were found to be infected, with flagellates of the genus Herpetomonas. Two distinct genotypes were documented, one of which was described as a new species, Herpetomonas tarakana sp. n. We also propose a revision of the genus Herpetomonas and creation of a new subfamily, Phytomonadinae, to include Herpetomonas, Phytomonas, and a newly described genus Lafontella n. gen. (type species Lafontella mariadeanei comb. n.), which can be distinguished from others by morphological and molecular traits. PMID- 26352485 TI - Influence of molecular structure on the properties of out-of-equilibrium oscillating enzymatic reaction networks. AB - Our knowledge of the properties and dynamics of complex molecular reaction networks, for example those found in living systems, considerably lags behind the understanding of elementary chemical reactions. In part, this is because chemical reactions networks are nonlinear systems that operate under conditions far from equilibrium. Of particular interest is the role of individual reaction rates on the stability of the network output. In this research we use a rational approach combined with computational methods, to produce complex behavior (in our case oscillations) and show that small changes in molecular structure are sufficient to impart large changes in network behavior. PMID- 26352486 TI - Quantum mechanical study of the beta- and delta-lyase reactions during the base excision repair process: application to FPG. AB - Bacterial FPG (or MutM) is a bifunctional DNA glycosylase that is primarily responsible for excising 8-oxoguanine (OG) from the genome by cleaving the glycosidic bond and the DNA backbone at the 3'- and 5'-phosphates of the damaged nucleoside. In the present work, quantum mechanical methods (SMD-M06-2X/6 311+G(2df,2p)//IEF-PCM-B3LYP/6-31G(d)) and a ring-opened Schiff base model that includes both the 3'- and 5'-phosphate groups are used to investigate the beta- and delta-elimination reactions facilitated by FPG. Both the beta- and delta elimination reactions are shown to proceed through an E1cB mechanism that involves proton abstraction prior to the phosphate-ribose bond cleavage. Since transition states for the phosphate elimination reactions could not be characterized in the absence of leaving group protonation, our work confirms that the phosphate elimination reactions require protonation by a residue in the FPG active site, and can likely be further activated by additional active-site interactions. Furthermore, our model suggests that 5'-PO4 activation may proceed through a nearly isoenergetic direct (intramolecular) proton transfer involving the O4' proton of the deoxyribose of the damaged nucleoside. Regardless, our model predicts that both 3'- and 5'-phosphate protonation and elimination steps occur in a concerted reaction. Most importantly, our calculated barriers for the phosphate cleavage reactions reveal inherent differences between the beta- and delta-elimination steps. Indeed, our calculations provide a plausible explanation for why the delta-elimination rather than the beta-elimination is the rate determining step in the BER facilitated by FPG, and why some bifunctional glycosylases (including the human counterpart, hOgg1) lack delta-lyase activity. Together, the new mechanistic features revealed by our work can be used in future large-scale modeling of the DNA-protein system to unveil the roles of key active sites residues in these relatively unexplored BER steps. PMID- 26352487 TI - Altering the course of disease in multiple sclerosis: many large steps forward. PMID- 26352488 TI - Stroke prevention and control in Brazil: missed opportunities. PMID- 26352489 TI - Natalizumab treatment in multiple sclerosis: the experience from two Brazilian MS centers. AB - Objective Analyze the demographics, clinical characteristics, efficacy and safety of natalizumab treatment in Brazilian patients with multiple sclerosis (MS) followed up for at least 12 months, in two tertiary MS care centers in Sao Paulo.Method We evaluated the effect of natalizumab treatment on annualized relapse rate and disability progression in 75 patients with MS treated with natalizumab for at least 12 months. A subgroup analysis was performed to evaluate efficacy of natalizumab treatment in patients with Expanded Disability Status Scale (EDSS) <= 3.0 vs patients with EDSS > 3.Results Patients treated for at least one year with natalizumab showed a 91% reduction in aRR, as well and an improvement in neurological disability. The impact of natalizumab treatment was greater in patients with EDSS < 3.0. Overall, natalizumab was safe but one patient developed progressive multifocal leukoencephalopathy.Conclusion Natalizumab as a third line therapy is safe and efficacious, especially in patients with mild neurological disability. PMID- 26352490 TI - Clinical and epidemiological profile of patients diagnosed with multiple sclerosis in Joao Pessoa, Paraiba, Brazil. AB - Prevalence rates of multiple sclerosis (MS) suggest an interrelationship between genetic and environmental factors, ranging worldwide.Objectives Clinical and epidemiological characterization of MS patients in Joao Pessoa, Paraiba city.Methods Study involving patients treated in five services in the city.Results It included 87 patients with MS, representing a prevalence of 12.0 cases/100,000 population, mainly women (77%) and white people (66.7%) with mean age of 43 years and average age of the first outbreak of 32.2 years. Motor symptoms (65.5%) and relapsing-remitting clinical form (78.2%) predominated; the average of the Expanded Disability Status Scale (EDSS) scores was 3.5 and 72% used a type of immunomodulatory drug. There was a positive correlation between the number of outbreaks and the duration of the disease with EDSS scores.Conclusions The prevalence of the disease is considered average. The clinical and epidemiological characteristics are in line with most similar Brazilian studies. PMID- 26352491 TI - Prevalence of stroke and associated disability in Brazil: National Health Survey- 2013. AB - There is scarce data about prevalence of stroke in Brazil. The National Health Survey (PNS) is a community-based epidemiological survey, with a nationally representative sample to assess the absolute numbers with respective prevalence rates of stroke and post-stroke disabilities. It was estimated 2,231.000 stroke and 568,000 stroke cases with severe disabilities. The point prevalences was 1.6% and 1.4% in men and women, respectively. The prevalences of post-stroke disabilities were 29.5% for men and 21.5% for women. Stroke prevalence rates increased with aging, low education level, among people living in urban areas with no difference according to self-reported skin color. The degree of post stroke disability was not statistically different according to sex, race, education level or living area. This new data from PNS show high stroke prevalence rates especially in older individuals without formal education and urban dweller, but the degree of stroke disability was not determined by the sociodemographic characteristics of the Brazilian population. PMID- 26352492 TI - Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) in Argentina. AB - CADASIL is the most common cause of hereditary stroke and vascular dementia. Published information about this disease in South America is scant. We describe clinical and demographic characteristics of 13 patients (10 families) with CADASIL from Argentina.Methods Medical records, diagnostic tests and family history of patients with CADASIL were reviewed.Results Thirteen patients with CADASIL (10 families) were included. All patients had European ancestry. Initial presentation was stroke in most patients (n = 11). Stroke patients later developed cognitive complaints (n = 9), migraine with aura (n = 1), apathy (n = 4) and depression (n = 6). External capsule and temporal lobe involvement on MRI were characteristic imaging findings. Two patients died after intracerebral hemorrhage.Conclusion This is the first report of non-related patients with CADASIL in South America addressing ancestry. Since European ancestry is not highly prevalent in all South American countries, there may be variable incidence of CADASIL within this region. PMID- 26352493 TI - Sodium nitroprusside: low price and safe drug to control BP during thrombolysis in AIS. AB - This study analyzes the use of sodium nitroprusside (SN) as an option to reduce blood pressure (BP) below 180/105 mmHg during the management of acute ischemic stroke (AIS) in patients submitted to intravenous thrombolysis.Method The sample was composed by 60 patients who had AIS and were submitted to intravenous rtPA, split in two groups: half in the control group (CG) with BP < 180/105 mmHg and half in SN group with BP > 180/105 mmHg. Outcome variables were any hemorrhagic transformation (HT); the presence of symptomatic HT, National Institute of Health Stroke Scale (NIHSS) after 24 hours of treatment; the independence on discharge and death until three months after stroke onset.Results There were no statistical differences between both groups to any of the outcome variables analyzed.Conclusion The SN might be safe for BP control during thrombolysis to AIS. PMID- 26352494 TI - Clinical and ultrasonographic criteria for using ventriculoperitoneal shunts in newborns with myelomeningocele. AB - Objective Hydrocephalus is one of the main complications associated with myelomeningocele (MM). This study aimed to identify clinical and ultrasonographic criteria for using ventriculoperitoneal (VP) shunts in this group of patients.Method A retrospective cohort study, based on established protocol for VP shunt implant in hydrocephalic children with MM. Parameters used to guide the indication of VP shunts included measurement of head circumference (HC), evaluation of fontanels, and measurement of lateral ventricular atrium (LVA) width by transcranial ultrasonography.Results 43 children were included in the analysis, of which 74% had hydrocephalus and required a VP shunt. These children had LVA width >= 15 mm, showed increased HC, or had bulging fontanels.Conclusion VP shunt is required in children with increased HC (>= 2 standard deviation regarding age group), bulging fontanels, or LVA width of >= 15 mm after the closure of MM. PMID- 26352495 TI - Surgical treatment of non-functioning pituitary macroadenomas by the endoscopic endonasal approach in the elderly. AB - Over the past three decades, surgical series of elderly patients treated for pituitary adenomas have been published, all of which used the microscopic transsphenoidal or transcranial approach. The objective of this study was to retrospectively analyze the surgical results of our first 25 elderly patients with non-functioning pituitary macroadenoma (NFPM) operated by the endoscopic endonasal approach (EEA). Preoperative visual loss was found in 92.8% of the cases, and 70.8% experienced visual improvement following surgery. Preoperative pituitary dysfunction was found in 69.2% of the cases and postoperative pituitary recovery occurred in 22.2% of them. Mean hospital stay was 6.7 days. The results of this study suggest that surgery remains the first line of treatment for NFPM in the elderly. Because age alone is not a barrier for surgery, patients should be selected for surgical treatment based on their symptoms and clinical condition, as defined by comorbidities. PMID- 26352496 TI - Atypical and anaplastic meningiomas in a public hospital in Sao Paulo State, Brazil. AB - Atypical/anaplastic (World Health Organization (WHO) grades II and III) are less common and have poorer outcomes than benign meningiomas. This study aimed to analyze the outcome of patients with these tumors. METHOD: Overall/recurrence free survivals (RFS) and the Karnofsky Performance Scale of 52 patients with grades II (42) and III (9) meningiomas surgically treated were analyzed (uni/multivariate analysis). RESULTS: Total/subtotal resections were 60.8%/35.3%. Patients <60 years-old and grade II tumors had longer survival. Grade II tumors, total resection and de novo meningioma had better RFS (univariate analysis). Patients >60 years-old, de novo meningioma and radiotherapy had longer survival and patients <60 years-old and with grade II tumors had longer RFS (multivariate analysis). Recurrence rate was 51% (39.2% Grade II and 66.7% Grade III). Operative mortality was 1.9%. CONCLUSION: Age <60 years-old, grade II tumors and de novo meningiomas were the main predictors for better prognosis among patients with grades II and III meningiomas. PMID- 26352497 TI - Effects of aging on nitrergic neurons in human striatum and subthalamic nucleus. AB - Nitric oxide (NO) is a major neurotransmitter associated with motor control in basal ganglia. Movement disorders, as essential tremor and Parkinson's disease, are more prevalent on aged individuals. We investigated the effects of aging on neuronal density and diameter/area of nitrergic neurons in samples of striatum (caudate and putamen) and subthalamic nucleus of 20 human brains from normal subjects, stained by histochemistry for NADPH-diaphorase and immunohistochemistry for neuronal NO synthase. Our data showed aging does not modify the neuronal density and size of nitrergic neurons in striatum and subthalamic nucleus. These findings suggest a lack of association between aging and morphologic changes on nitrergic neurons. PMID- 26352498 TI - Lipopolysaccharide-induced memory impairment in rats is preventable using 7 nitroindazole. AB - Inflammation and oxidative stress have important roles in memory impairment. The effect of 7-nitroindazole (7NI) on lipopolysaccharide (LPS)-induced memory impairment was investigated. Rats were used, divided into four groups that were treated as follows: (1) control (saline); (2) LPS; (3) 7NI-LPS; and (4) 7NI before passive avoidance (PA). In the LPS group, the latency for entering the dark compartment was shorter than in the controls (p < 0.01 and p < 0.001); while in the 7NI-LPS group, it was longer than in the LPS group (p < 0.01 and p < 0.001). Malondialdehyde (MDA) and nitric oxide (NO) metabolite concentrations in the brain tissues of the LPS group were higher than in the controls (p < 0.001 and p < 0.05); while in the 7NI-LPS group, they were lower than in the LPS group (p < 0.001 and p < 0.05, respectively). The thiol content in the brain of the LPS group was lower than in the controls (p < 0.001); while in the 7NI-LPS group, it was higher than in the LPS group (p < 0.001). It is suggested that brain tissue oxidative damage and NO elevation have a role in the deleterious effects of LPS on memory retention that are preventable using 7NI. PMID- 26352499 TI - Shared decision-making in the context of unruptured intracranial aneurysms management. AB - Shared decision-making practice has been encouraged in several clinical settings. In this model, clinical decisions are defined by doctors and patients based on the principle of patient autonomy. Shared decisions have been argued as an ethical clinical practice during complex and uncertain clinical situations. The best management of unruptured intracranial aneurysms (UIA) remains controversial. Despite the fact that shared decisions has probably been practiced, as far as we are aware it has not yet been evaluated, nor has it been standardized for patients presenting UIA. We aim to discuss possible roles, pros and cons of shared decision-making on the management of UIA. PMID- 26352500 TI - An update in the management of spinal metastases. AB - The best clinical treatment for spinal metastases requires an integrated approach with input from an interdisciplinary cancer team. The principle goals of treatment are maintenance or improvement in neurologic function and ambulation, spinal stability, durable tumor control, and pain relief. The past decade has witnessed an explosion of new technologies that have impacted our ability to reach these goals, such as separation surgery and minimally invasive spinal procedures. The biggest advance, however, has been the evolution of stereotactic radiosurgery that has demonstrated durable tumor control both when delivered as definitive therapy and as a postoperative adjuvant even for tumors considered markedly resistant to conventional external beam radiation. In this paper, we perform an update on the management of spinal metastases demonstrating the integration of these new technologies into a decision framework NOMS that assesses four basic aspects of a patient's spine disease: Neurologic, Oncologic, Mechanical Instability and Systemic disease. PMID- 26352501 TI - Neonatal brachial plexus palsy: a permanent challenge. AB - Neonatal brachial plexus palsy (NBPP) has an incidence of 1.5 cases per 1000 live births and it has not declined despite recent advances in obstetrics. Most patients will recover spontaneously, but some will remain severely handicapped. Rehabilitation is important in most cases and brachial plexus surgery can improve the functional outcome of selected patients. This review highlights the current management of infants with NBPP, including conservative and operative approaches. PMID- 26352502 TI - Jean-Baptiste Charcot in Rio de Janeiro: glamorous trip and celebrity in 1908. AB - The authors review the visit of Commander Charcot and the crew of his ship, the "Pourquoi Pas?", to Rio de Janeiro, Brazil, in 1908, where he stayed for eight days, while en-route as part of the second French expedition to the Antarctic. It was a glamorous stay as Commander Charcot was treated as a true star and international celebrity, befitting his position. PMID- 26352503 TI - Longitudinally extensive transverse myelopathy in a patient with CADASIL. PMID- 26352504 TI - CNS and cutaneous involvement in tuberous sclerosis complex. PMID- 26352505 TI - Michelangelo, ocular bulb, retina and the Creator. PMID- 26352506 TI - Reply: To PMID 25742593. PMID- 26352507 TI - Evaluation of the Percutaneous Absorption of Ketamine HCl, Gabapentin, Clonidine HCl, and Baclofen, in Compounded Transdermal Pain Formulations, Using the Franz Finite Dose Model. AB - OBJECTIVE: This study evaluates the ability of four commonly used analgesics (ketamine HCl, gabapentin, clonidine HCl, and baclofen), when incorporated into two transdermal compounding bases, Lipoderm and Lipoderm ActiveMax, to penetrate human cadaver trunk skin in vitro, using the Franz finite dose model. DESIGN: In vitro experimental study. Methods. Ketamine HCl 5% w/w, gabapentin 10% w/w, clonidine HCl 0.2% w/w, and baclofen 2% w/w were compounded into two transdermal bases, Lipoderm and Lipoderm ActiveMax. Each compounded drug formulation was tested on skin from three different donors and three replicate skin sections per donor. The Franz finite dose model was used in this study to evaluate the percutaneous absorption and distribution of drugs within each formulation. RESULTS: Rapid penetration to peak flux was detected for gabapentin and baclofen at approximately 1 hour after application. Clonidine HCl also had a rapid penetration to peak flux occurring approximately 1 hour after application and had a secondary peak at approximately 40 hours. Ketamine HCl exhibited higher overall absorption rates than the other drugs, and peaked at 6-10 hours. Similar patterns of drug distribution within the skin were also observed using both transdermal bases. CONCLUSIONS: This study suggests that the combination of these 4 analgesic drugs can be successfully delivered transdermally, using either Lipoderm or Lipoderm ActiveMax. Compounded transdermal drug preparations may then provide physicians with an alternative to traditional oral pain management regimens that can be personalized to the specific patient with the potential for enhanced pain control. PMID- 26352508 TI - Generation of phase II in vitro metabolites using homogenized horse liver. AB - The successful use of homogenized horse liver for the generation of phase I in vitro metabolites has been previously reported by the authors' laboratory. Prior to the use of homogenized liver, the authors' laboratory had been using mainly horse liver microsomes for carrying out equine in vitro metabolism studies. Homogenized horse liver has shown significant advantages over liver microsomes for in vitro metabolism studies as the procedures are much quicker and have higher capability for generating more in vitro metabolites. In this study, the use of homogenized liver has been extended to the generation of phase II in vitro metabolites (glucuronide and/or sulfate conjugates) using 17beta-estradiol, morphine, and boldenone undecylenate as model substrates. It was observed that phase II metabolites could also be generated even without the addition of cofactors. To the authors' knowledge, this is the first report of the successful use of homogenized horse liver for the generation of phase II metabolites. It also demonstrates the ease with which both phase I and phase II metabolites can now be generated in vitro simply by using homogenized liver without the need for ultracentrifuges or tedious preparation steps. PMID- 26352509 TI - Happy bedfellows. PMID- 26352510 TI - Geminal bis(silane)-controlled regio- and stereoselective oxidative Heck reaction of enol ethers with terminal alkenes to give push-pull 1,3-dienes. AB - A geminal bis(silane)-controlled regio- and stereoselective oxidative Heck reaction of enol ethers with terminal alkenes has been developed. The reaction proceeds with alpha,beta-coupling regioselectivity to give push-pull Z,E-1,3 dienes in good yields. The product showed valuable utility in Sakurai homoallylation with acetals to generate alpha-substituted-gamma-keto esters with good anti-selectivity. PMID- 26352512 TI - Research Resource: A Chromogranin A Reporter for Serotonin and Histamine Secreting Enteroendocrine Cells. AB - Chromogranin A (ChgA) is an acidic protein found in large dense-core secretory vesicles and generally considered to be expressed in all enteroendocrine cells of the gastrointestinal (GI) tract. Here, we characterize a novel reporter mouse for ChgA, ChgA-humanized Renilla reniformis (hr)GFP. The hrGFP reporter was found in the monoamine-storing chromaffin cells of the adrenal medulla, where ChgA was originally discovered. hrGFP also was expressed in enteroendocrine cells throughout the GI tract, faithfully after the expression of ChgA, as characterized by immunohistochemistry and quantitative PCR analysis of fluorescence-activated cell sorting-purified cells, although the expression in the small intestine was weak compared with that of the stomach and colon. In the stomach, hrGFP was highly expressed in almost all histamine-storing enterochromaffin (EC)-like cells, at a lower level in the majority of serotonin storing EC cells and ghrelin cells, in a small fraction of somatostatin cells, but was absent from gastrin cells. In the small intestine, the hrGFP reporter was selectively, but weakly expressed in EC cells, although not in any peptide storing enteroendocrine cells. In the colon, hrGFP was exclusively expressed in EC cells but absent from the peptide-storing enteroendocrine cells. In contrast, in the pancreas, hrGFP was expressed in beta-cells, alpha-cells, and a fraction of pancreatic polypeptide cells. It is concluded that ChgA-hrGFP in the GI tract functions as an effective reporter, particularly for the large populations of still poorly characterized monoamine-storing enteroendocrine cells. Furthermore, our findings substantiate the potential function of ChgA as a monoamine-binding protein that facilitates the regulated endocrine secretion of large amounts of monoamines from enteroendocrine cells. PMID- 26352513 TI - Determination of the minimum infusion rate of alfaxalone during its co administration with fentanyl at three different doses by constant rate infusion intravenously in goats. AB - OBJECTIVE: To determine the minimum infusion rate (MIR) of alfaxalone required to prevent purposeful movement of the extremities in response to standardized noxious stimulation during its co-administration with fentanyl at three different doses by constant rate infusion (CRI) intravenously (IV) in goats. STUDY DESIGN: Prospective, blinded, randomized crossover, experimental. ANIMALS: Eight healthy goats; four does and four wethers. METHODS: For induction of anaesthesia, a bolus of fentanyl was administered at 0.005 mg kg(-1) (LFent), 0.015 mg kg(-1) (MFent) or 0.03 mg kg(-1) (HFent) followed by alfaxalone at 2.0 mg kg(-1) . For maintenance, the goats received alfaxalone at an initial infusion rate of 9.6 mg kg(-1) hour(-1) and one of three fentanyl treatments: 0.005 mg kg(-1) hour(-1) (LFent), 0.015 mg kg(-1) hour(-1) (MFent) or 0.03 mg kg(-1) hour(-1) (HFent). The MIR of alfaxalone was determined during fentanyl CRI by testing for responses to stimulation (clamping on a digit with Vulsellum forceps) every 30 minutes. Some cardiopulmonary parameters were measured. RESULTS: The alfaxalone MIR median (range) was 6.7 (6.7-8.6), 2.9 (1.0-6.7) and 1.0 (1.0-4.8) mg kg(-1) hour(-1) during LFent, MFent and HFent, respectively. Alfaxalone MIR was significantly lower during MFENT and HFENT compared to LFENT. Significantly low oxygen haemoglobin saturation (SaO2 ) and arterial oxygen partial pressure (PaO2 ), observed 2 minutes into anaesthesia after all fentanyl treatments, were the most remarkable adverse cardiopulmonary effects observed. Recovery from anaesthesia was severely affected by high doses of fentanyl with excitatory behavioural signs predominant for up to 2 hours post-administration after MFent and HFent. CONCLUSIONS AND CLINICAL RELEVANCE: Fentanyl reduces alfaxalone MIR in goats in a dose-dependent manner. Immediate oxygen supplementation after induction of general anaesthesia is recommended to prevent hypoxaemia. Doses of fentanyl equal to or greater than 0.015 mg kg(-1) hour(-1) tend to be associated with severe excitatory behaviour and should be avoided when fentanyl is administered to goats. PMID- 26352514 TI - Temperature-Dependent Postmortem Changes in Human Cardiac Troponin-T (cTnT): An Approach in Estimation of Time Since Death. AB - Estimation of time of death is an indispensible requirement of every medico-legal autopsy, but unfortunately, there is not a single method by which it could be determined accurately. This study focused on the temperature-dependent postmortem degradation of cardiac troponin-T and its association with postmortem interval (PMI) in human. The analysis involved extraction of the protein, separation by denaturing gel electrophoresis (SDS-PAGE), and visualization by Western blot using cTnT-specific monoclonal antibodies. The area of the bands within a lane was quantified by scanning and digitizing the image using Gel Doc (Universal Hood). The results indicate a characteristic banding pattern among human cadavers (n = 6) and a pseudo-linear relationship between percentage of cTnT degradation and the log of the time since death (r > 0.95), which can be used to estimate the postmortem interval. The data presented demonstrate that this technique can provide an extended time range during which PMI can be more accurately estimated. PMID- 26352515 TI - New structural types of Mn16 single-molecule magnets: W-shaped topology from reductive aggregation. AB - Two new Mn16 clusters are reported: [Mn16O10(OH)3(OMe)8(O2CPhBut)17(MeOH)5] (2) and [Mn16O16(OMe)6(O2CPh)12(NO3)4(MeOH)2(H2O)4] (3). The complexes were obtained by reductive aggregation of MnO4- in CH2Cl2/MeOH, and oxidation of MnII and preformed (NnBu4)[Mn4IIIO2(O2CPh)9(H2O)] with CeIV, respectively. The core of 2 has a Mn16III core with an unusual 1:2:3:4:3:2:1 layer structure and a W-shaped pleated topology, whereas 3 contains a central 2 * 3 Mn6IV planar grid held within a nonplanar Mn10III loop and is a rare example of a complex with nitrate ions bridging like carboxylate ions. Variable-temperature, solid-state dc susceptibility, and ac susceptibility studies reveal that 2 and 3 possess S = 12 and S = 8 ground states, respectively. Fits of dc magnetization data collected over a temperature range of 1.8-4.0 K and a magnetization range of 0.1-4 T were fit to give S = 12, D = -0.16(2) cm-1, g = 1.98(3) for 2 and S = 8, D = -0.22(1) cm-1, g = 1.99(2) for 3, where D is the axial zero-field splitting parameter. The ac in-phase (chiM'T) susceptibility below 15 K confirmed the ground-state spin values of 2 and 3, as determined from dc data, and the appearance of frequency dependent out-of-phase (chiM") signals revealed that both complexes are new single-molecule magnets (SMMs). Fits of the ac data gave Ueff = 49.7(1) K and tau0 = 4.32 * 10-9 s for 2 and Ueff ~ 14.0 +/- 2 cm-1 and tau0 ~ 3.2 +/- 0.5 * 10 8 s for 3, where Ueff is the effective barrier to magnetization relaxation and tau0 is the pre-exponential factor. Thus, complexes 2 and 3 are two new members of a growing family of Mn16 clusters, and two new examples of high-nuclearity SMMs, with the Ueff for 2 approaching the value for the prototypical SMM family, [Mn12O12(O2CR)16(H2O)4]. PMID- 26352511 TI - Rising Obesity Prevalence and Weight Gain Among Adults Starting Antiretroviral Therapy in the United States and Canada. AB - The proportion of overweight and obese adults in the United States and Canada has increased over the past decade, but temporal trends in body mass index (BMI) and weight gain on antiretroviral therapy (ART) among HIV-infected adults have not been well characterized. We conducted a cohort study comparing HIV-infected adults in the North America AIDS Cohort Collaboration on Research and Design (NA ACCORD) to United States National Health and Nutrition Examination Survey (NHANES) controls matched by sex, race, and age over the period 1998 to 2010. Multivariable linear regression assessed the relationship between BMI and year of ART initiation, adjusting for sex, race, age, and baseline CD4(+) count. Temporal trends in weight on ART were assessed using a generalized least-squares model further adjusted for HIV-1 RNA and first ART regimen class. A total of 14,084 patients from 17 cohorts contributed data; 83% were male, 57% were nonwhite, and the median age was 40 years. Median BMI at ART initiation increased from 23.8 to 24.8 kg/m(2) between 1998 and 2010 in NA-ACCORD, but the percentage of those obese (BMI >=30 kg/m(2)) at ART initiation increased from 9% to 18%. After 3 years of ART, 22% of individuals with a normal BMI (18.5-24.9 kg/m(2)) at baseline had become overweight (BMI 25.0-29.9 kg/m(2)), and 18% of those overweight at baseline had become obese. HIV-infected white women had a higher BMI after 3 years of ART as compared to age-matched white women in NHANES (p = 0.02), while no difference in BMI after 3 years of ART was observed for HIV infected men or non-white women compared to controls. The high prevalence of obesity we observed among ART-exposed HIV-infected adults in North America may contribute to health complications in the future. PMID- 26352516 TI - Effect of Lactobacillus plantarum on Intestinal Infection in Multiple Drug Resistant Bacteria Mice. AB - BACKGROUND: This study aimed to determine the effects of probiotic Lactobacillus plantarum on colitis in mice with multiple drug-resistant bacteria, and to judge the intervention function of probiotics in the resistance of pathogenic bacteria. METHODS: Male BALB/C mice were divided into four groups. The colonic tissues were collected for pathology observation, permeability, transepithelial electrical resistance (TER), and tight junction protein expression detection at death, and the feces were collected for detecting drug susceptibility of MDR-PA. RESULTS: MDR-PA mice developed severe intestinal inflammation and tissue damage in which paracellular permeability was increased, in conjunction with decreased expression and redistribution. LP administration attenuated colitis of MDR-PA mice. The drug susceptibility diameter of MDR-PA has increased. CONCLUSION: Probiotics can treat diarrhea of mice by MDR-PA and protect the intestinal barrier function. Probiotics can weaken the resistance of multiple drug resistance in Pseudomonas aeruginosa to some extent. PMID- 26352517 TI - Mussel adhesion-employed water-immiscible fluid bioadhesive for urinary fistula sealing. AB - Urinary fistulas, abnormal openings of a urinary tract organ, are serious complications and conventional management strategies are not satisfactory. For more effective and non-invasive fistula repair, fluid tissue adhesives or sealants have been suggested. However, conventional products do not provide a suitable solution due to safety problems and poor underwater adhesion under physiological conditions. Herein, we proposed a unique water-immiscible mussel protein-based bioadhesive (WIMBA) exhibiting strong underwater adhesion which was employed by two adhesion strategies of marine organisms; 3,4-dihydroxy-l phenylalanine (DOPA)-mediated strong adhesion and water-immiscible coacervation. The developed biocompatible WIMBA successfully sealed ex vivo urinary fistulas and provided good durability and high compliance. Thus, WIMBA could be used as a promising sealant for urinary fistula management with further expansion to diverse internal body applications. PMID- 26352519 TI - Age-Related Differences in Postural Control and Attentional Cost During Tasks Performed in a One-Legged Standing Posture. AB - BACKGROUND AND PURPOSE: In dual-task situations, postural control is closely associated with attentional cost. Previous studies have reported age-related differences between attentional cost and postural control, but little is known about the association in conditions with a one-legged standing posture. The purpose of this study was to determine age-related differences in postural control and attentional cost while performing tasks at various difficulty levels in a one-legged standing posture. METHODS: In total, 29 healthy older adults aged 64 to 78 years [15 males, 14 females, mean (SD) = 71.0 (3.8) years] and 29 healthy young adults aged 20 to 26 years [14 males, 15 females, mean (SD) = 22.5 (1.5) years] participated in this study. We measured the reaction time, trunk accelerations, and lower limb muscle activity under 3 different one-legged standing conditions-on a firm surface, on a soft surface with a urethane mat, and on a softer more unstable surface with 2 piled urethane mats. Reaction time as an indication of attentional cost was measured by pressing a handheld button as quickly as possible in response to an auditory stimulus. A 2-way repeated measures analysis of variance was performed to examine the differences between the 3 task conditions and the 2 age groups for each outcome. RESULTS AND DISCUSSION: Trunk accelerations showed a statistically significant group-by condition interaction in the anteroposterior (F = 9.1, P < .05), mediolateral (F = 9.9, P < .05), and vertical (F = 9.3, P < .05) directions. Muscle activity did not show a statistically significant group-by-condition interaction, but there was a significant main effect of condition in the tibialis anterior muscle (F = 33.1, P < .01) and medial gastrocnemius muscle (F = 14.7, P < .01) in young adults and the tibialis anterior muscle (F = 24.8, P < .01) and medial gastrocnemius muscle (F = 10.8, P < .01) in older adults. In addition, there was a statistically significant interaction in reaction time (F = 8.2, P < .05) for group-by-condition. CONCLUSIONS: The study results confirmed that reaction times in older adults are more prolonged than young adults in the same challenging postural control condition. PMID- 26352518 TI - A modular, plasmin-sensitive, clickable poly(ethylene glycol)-heparin-laminin microsphere system for establishing growth factor gradients in nerve guidance conduits. AB - Peripheral nerve regeneration is a complex problem that, despite many advancements and innovations, still has sub-optimal outcomes. Compared to biologically derived acellular nerve grafts and autografts, completely synthetic nerve guidance conduits (NGC), which allow for precise engineering of their properties, are promising but still far from optimal. We have developed an almost entirely synthetic NGC that allows control of soluble growth factor delivery kinetics, cell-initiated degradability and cell attachment. We have focused on the spatial patterning of glial-cell derived human neurotrophic factor (GDNF), which promotes motor axon extension. The base scaffolds consisted of heparin containing poly(ethylene glycol) (PEG) microspheres. The modular microsphere format greatly simplifies the formation of concentration gradients of reversibly bound GDNF. To facilitate axon extension, we engineered the microspheres with tunable plasmin degradability. 'Click' cross-linking chemistries were also added to allow scaffold formation without risk of covalently coupling the growth factor to the scaffold. Cell adhesion was promoted by covalently bound laminin. GDNF that was released from these microspheres was confirmed to retain its activity. Graded scaffolds were formed inside silicone conduits using 3D-printed holders. The fully formed NGC's contained plasmin-degradable PEG/heparin scaffolds that developed linear gradients in reversibly bound GDNF. The NGC's were implanted into rats with severed sciatic nerves to confirm in vivo degradability and lack of a major foreign body response. The NGC's also promoted robust axonal regeneration into the conduit. PMID- 26352520 TI - Double-Well Ultracold-Fermions Computational Microscopy: Wave-Function Anatomy of Attractive-Pairing and Wigner-Molecule Entanglement and Natural Orbitals. AB - "Bottom-up" approaches to the many-body physics of fermions have recently demonstrated precise number and site-resolved preparations with tunability of interparticle interactions in single-well, SW, and double-well, DW, nanoscale confinements created by manipulating ultracold fermionic atoms with optical tweezers. These experiments emulate an analogue-simulator mapping onto the requisite microscopic Hamiltonian, approaching realization of Feynmans' vision of quantum simulators that "will do exactly the same as nature". Here we report on exact benchmark configuration-interaction computational microscopy solutions of the Hamiltonian, uncovering the spectral evolution, wave function anatomy, and entanglement properties of the interacting fermions in the entire parameter range, including crossover from an SW to a DW confinement and a controllable energy imbalance between the wells. We demonstrate attractive pairing and formation of repulsive, highly correlated, ultracold Wigner molecules, well described in the natural orbital representation. The agreement with the measurements affirms the henceforth gained deep insights into ultracold molecules and opens access to the size-dependent evolution of nanoclustered and condensed matter phases and ultracold-atoms quantum information. PMID- 26352521 TI - MALOCCLUSION, PAST ORTHODONTIC TREATMENT, AND SATISFACTION WITH DENTAL APPEARANCE AMONG CANADIAN ADULTS. AB - OBJECTIVE: To examine whether malocclusion and past orthodontic treatment are associated with satisfaction with dental appearance among Canadian adults. METHODS: Using data from the 2007-09 Canadian Health Measures Survey, this cross sectional study analyzed information from 2184 respondents (1005 men and 1179 women) aged 20-59 years. The outcome variable was satisfaction with dental appearance. Ordinal logistic regression was used to investigate the relation between satisfaction with dental appearance and 2 independent variables: malocclusion and past orthodontic treatment. RESULTS: Of the participants, 70% were "very satisfied" or "satisfied" with the appearance of their teeth. The prevalence of malocclusion and past orthodontic treatment was 25% and 20%, respectively. Controlling for the effect of covariates, malocclusion had a significant negative effect on satisfaction with dental appearance (p = 0.02), but past orthodontic treatment did not (p = 0.36). Satisfaction with dental appearance was greater among those in the higher-income group, never smokers, those with better self-rated health, those with no anterior decayed teeth, and those with no anterior filled teeth. CONCLUSION: Past orthodontic treatment was not linked to satisfaction with dental appearance in this sample of Canadian adults. Public health programs and clinicians should focus on addressing esthetic problems by restoring inadequate anterior teeth fillings, restoring anterior tooth decay, and implementing smoking cessation programs before considering orthodontic treatment. PMID- 26352522 TI - WHAT ARE CANADIAN DENTAL PROFESSIONAL STUDENTS TAUGHT ABOUT INFANT, TODDLER AND PRENATAL ORAL HEALTH. AB - INTRODUCTION: Establishing dental homes for children at an early age is an important step toward instilling good oral health practices and changing trajectories of oral health. The purpose of this study was to determine how accredited dental and dental hygiene programs in Canada prepare students in the areas of infant, toddler and prenatal oral health. METHODS: An electronic questionnaire was sent to associate deans (academic), program directors or curriculum directors of accredited dental (n = 10) and dental hygiene (n = 39) programs. Participants were asked about infant, toddler and prenatal oral health curricula taught at their institution. Descriptive statistics and bivariate analyses were used to assess the results. A p value = 0.05 was considered significant. RESULTS: Representatives of 10 dental (100%) and 25 dental hygiene (64.1%) programs responded. All dental and 56% of dental hygiene programs recommend a first visit by 12 months. Infant and toddler oral health was noted as a component of most schools' curriculum. Barriers to teaching about or providing clinical experiences in infant and toddler oral health include lack of time, patients, program resources and finances. Most dental (70%) and dental hygiene (82.6%) programs include prenatal oral health as a component of their curriculum, yet only 40% of responding dental and 70% of dental hygiene programs reported having designated time in their curriculum for it. Barriers preventing programs from teaching or providing clinical experiences regarding prenatal oral health include lack of time and patients. CONCLUSIONS: Many, but not all dental professional programs are teaching their students about the recommended age for a first dental visit. Better adherence to national guidelines will require programs to address current barriers impeding learning about this important topic and to provide creative opportunities for students regarding prenatal and infant and toddler oral health. PMID- 26352523 TI - Semi-Transparent ZnO-CuI/CuSCN Photodiode Detector with Narrow-Band UV Photoresponse. AB - The ZnO homogeneous pn junction photodiode is quite difficult to fabricate due to the absence of stable p-type ZnO. So exploring reliable p-type materials is necessary to build a heterogeneous pn junction with n-type ZnO. Herein, we develop a simple and low-cost solution-processed method to obtain inorganic p type CuI/CuSCN composite film with compact morphology, high conductivity, and low surface state. The improved performance of CuI/CuSCN composite film can be confirmed based on high-rectification ratio, responsivity, and open voltage of ZnO-CuI/CuSCN photodiode UV detectors. Moreover, photodiodes with novel top electrodes are investigated. Compared with commonly used Au and graphene/Ag nanowire (NWs) electrode, poly(3,4-ethylenedioxythiophene):poly(4 styrenesulfonate) ( PEDOT: PSS) electrode prepared by Meyer rod-coating technique opens one route to obtain a semitransparent photodiode. The photodiode with PEDOT: PSS as the top electrode under reverse illumination has the highest photocurrent density due to higher UV transmittance of PEDOT: PSS transparent electrode compared with ITO glass. The low-energy consumption, and high responsivity, UV to visible rejection ratio and air stability make this ZnO CuI/CuSCN photodiode quite promising in the UV-A detection field. PMID- 26352524 TI - Re: "Granulocytic Sarcoma of the Orbit Presenting as a Fulminant Orbitopathy in an Adult with Acute Myeloid Leukemia". PMID- 26352525 TI - Reply Re: "Granulocytic Sarcoma of the Orbit Presenting as a Fulminant Orbitopathy in an Adult with Acute Myeloid Leukemia". PMID- 26352526 TI - Re: "Safety of Onabotulinum Toxin A Injections to the Central Upper Eyelid and Eyebrow Regions". PMID- 26352527 TI - Muir-Torre Syndrome Masquerading as Chalazion. PMID- 26352528 TI - Long-Term Outcomes of Circumostial Injection of Mitomycin C (COS-MMC) in Dacryocystorhinostomy. PMID- 26352529 TI - Decreased Morbidity of Laparoscopic Distal Gastrectomy Compared With Open Distal Gastrectomy for Stage I Gastric Cancer: Short-term Outcomes From a Multicenter Randomized Controlled Trial (KLASS-01). AB - OBJECTIVE: To determine the safety of laparoscopy-assisted distal gastrectomy (LADG) compared with open distal gastrectomy (ODG) in patients with clinical stage I gastric cancer in Korea. BACKGROUND: There is still a lack of large scale, multicenter randomized trials regarding the safety of LADG. METHODS: A large-scale, phase 3, multicenter, prospective randomized controlled trial was conducted. The primary end point was 5-year overall survival. Morbidity within 30 postoperative days and surgical mortality were compared to evaluate the safety of LADG as a secondary end point RESULTS: : A total of 1416 patients were randomly assigned to the LADG group (n = 705) or the ODG group (n = 711) between February 1, 2006, and August 31, 2010, and 1384 patients were analyzed for modified intention-to-treat analysis (ITT) and 1256 were eligible for per protocol (PP) analysis (644 and 612, respectively). In the PP analysis, 6 patients (0.9%) needed open conversion in the LADG group. The overall complication rate was significantly lower in the LADG group (LADG vs ODG; 13.0% vs 19.9%, P = 0.001). In detail, the wound complication rate of the LADG group was significantly lower than that of the ODG group (3.1% vs 7.7%, P < 0.001). The major intra-abdominal complication (7.6% vs 10.3%, P = 0.095) and mortality rates (0.6% vs 0.3%, P = 0.687) were similar between the 2 groups. Modified ITT analysis showed similar results with PP analysis. CONCLUSIONS: LADG for patients with clinical stage I gastric cancer is safe and has a benefit of lower occurrence of wound complication compared with conventional ODG. PMID- 26352530 TI - Poor permeability and absorption affect the activity of four alkaloids from Coptis. AB - Coptidis rhizoma (Coptis) and its alkaloids exert various pharmacological functions in cells and tissues; however, the oral absorption of these alkaloids requires further elucidation. The present study aimed to examine the mechanism underlying the poor absorption of alkaloids, including berberine (BER), coptisine (COP), palmatine (PAL) and jatrorrhizine (JAT). An ultra-performance liquid chromatography (UPLC) method was validated for the determination of BER, COP, PAL and JAT in the above experimental medium. In addition, the apparent oil-water partition coefficient (Po/w); apparent permeability coefficient (Papp), determined using a parallel artificial membrane permeability assay (PAMPA) plate; membrane retention coefficient (R %); and effect of P-glycoprotein (P-gp) inhibitor on the Papp of the four alkaloids were investigated. The intestinal absorption rate constant (Ka) and absorption percentage (A %) of the four alkaloids were also determined. The results of the present study demonstrated that the Po/w of the four alkaloids in 0.1 mol.l-1 HCl medium was significantly higher (P<0.01), compared with those of the alkaloids in phosphate buffer (pH 7.4). The Papp of BER was 1.0-1.2x10-6 cm.s-1, determined using a PAMPA plate, and the Papp of BER, COP, PAL and JAT decreased sequentially. The concentrations of the four alkaloids on the apical-to-basolateral (AP-BL) surface and the basolateral-to-apical (BL-AP) surface increased in a linear manner, with increasing concentrations between 10 and 100 umol. In addition, the transportation of BER on the BL-AP surface was significantly faster (P<0.01), compared with that on the AP-BL surface and, following the addition of verpamil (a P-gp inhibitor), the Papp (AP-BL) of the four alkaloids increased, whereas the Papp (BL-AP) was significantly decreased (P<0.01). The rat intestinal perfusion experiment demonstrated that the four alkaloids were poorly absorbed; however, the Ka of BER was significantly higher, compared with the three other alkaloids. Furthermore, the A % and Ka provided evidence that the absorption of BER was increased in the jejunum, compared with in the ileum. In conclusion, the four alkaloids from Coptis appeared to be poorly absorbed, determined using a shake flask, pre-coated PAMPA plates, a Caco-2 cell monolayer model and intestinal perfusion; however, absorption was higher in the jejunum than in the ileum. Among the four alkaloids, the permeability of BER was markedly higher than the others, and P-gp efflux had a significant effect on the absorption of those alkaloids. PMID- 26352531 TI - Salinomycin inhibits the growth of colorectal carcinoma by targeting tumor stem cells. AB - Salinomycin is a monocarboxylic polyether antibiotic that has been reported to induce apoptosis in various types of cancer cells with specificity for cancer stem cells. However, its anticancer effect in colorectal cancer stem cells has never been reported. In the present study, we examined the ability of salinomycin to induce cell death in the colorectal cancer stem cell line CD44+EpCAM+ HCT-116, and we measured its in vivo tumor inhibition capacity. Salinomycin dose dependently induced cytotoxicity in the CD44+EpCAM+ HCT-116 cells and inhibited colony formation. Salinomycin treatment was shown to induce apoptosis, as evidenced by nuclear fragmentation, an increase in the proportion of acridine orange/ethidium bromide-positive cells and an increase in the percentage of Annexin V-positive cells. Apoptosis was induced in colorectal cancer stem cells in a caspase-dependent manner, as shown by an increase in the levels of cleaved caspase-3, -8 and -9. JC-1 staining further revealed that salinomycin induced colorectal cancer cell apoptosis via the mitochondrial pathway. In addition, salinomycin treatment of xenograft mice inhibited the growth of tumors derived from the CD44+EpCAM+ HCT-116 cells. The present study demonstrated that the antibiotic salinomycin exerts an anti-colorectal cancer effect in vitro and in vivo, suggesting salinomycin as a potential drug for colorectal cancer therapy. PMID- 26352532 TI - Lung Cancer Risk Prediction Using Common SNPs Located in GWAS-Identified Susceptibility Regions. AB - INTRODUCTION: Genome-wide association studies (GWAS) have consistently identified specific lung cancer susceptibility regions. We evaluated the lung cancer predictive performance of single-nucleotide polymorphisms (SNPs) in these regions. METHODS: Lung cancer cases (N = 778) and controls (N = 1166) were genotyped for 77 SNPs located in GWAS-identified lung cancer susceptibility regions. Variable selection and model development used stepwise logistic regression and decision-tree analyses. In a subset nested in the Pittsburgh Lung Screening Study, change in area under the receiver operator characteristic curve and net reclassification improvement were used to compare predictions made by risk factor models with and without genetic variables. RESULTS: Variable selection and model development kept two SNPs in each of three GWAS regions, rs2736100 and rs7727912 in 5p15.33, rs805297 and rs1802127 in 6p21.33, and rs8034191 and rs12440014 in 15q25.1. The ratio of cases to controls was three times higher among subjects with a high-risk genotype in every one as opposed to none of the three GWAS regions (odds ratio, 3.14; 95% confidence interval, 2.02 4.88; adjusted for sex, age, and pack-years). Adding a three-level classified count of GWAS regions with high-risk genotypes to an age and smoking risk factor only model improved lung cancer prediction by a small amount: area under the receiver operator characteristic curve, 0.725 versus 0.717 (p = 0.056); overall net reclassification improvement was 0.052 across low-, intermediate-, and high- 6-year lung cancer risk categories (<3.0%, 3.0%-4.9%, >= 5.0%). CONCLUSION: Specifying genotypes for SNPs in three GWAS-identified susceptibility regions improved lung cancer prediction, but probably by an extent too small to affect disease control practice. PMID- 26352533 TI - EML4-ALK Fusion Detected by RT-PCR Confers Similar Response to Crizotinib as Detected by FISH in Patients with Advanced Non-Small-Cell Lung Cancer. AB - INTRODUCTION: Reverse transcriptase polymerase chain reaction (RT-PCR) assay has been proved to have high sensitivity and specificity to detect anaplastic lymphoma kinase (ALK) rearrangements. The aim of this study was to investigate the response to crizotinib in patients of advanced non-small-cell lung cancer (NSCLC) with ALK rearrangements detected by RT-PCR. METHODS: Only patients with advanced NSCLC who had their ALK rearrangement status detected by RT-PCR were included in this analysis. The utility of RT-PCR and fluorescence in situ hybridization (FISH) assay were compared in patients who were treated with crizotinib based on their positive ALK rearrangements. RESULTS: One thousand ten patients were included in this study. Among them, 104 patients were ALK RT-PCR positive and 53 of them received crizotinib treatment. Among 255 tumors simultaneously analyzed by FISH and RT-PCR, the latter successfully detected all the 25 tumors with arrangements, including two cases that were missed by FISH. The overall response rate and median progression-free survival of the 53 patients with ALK rearrangements who received crizotinib treatment were 60.4% (95% confidence interval [CI], 47.2-73.6) and 8.4 months (95% CI, 6.75-10.05), respectively, which were similar to the 21 patients detected by FISH with overall response rate of 57.1% (95% CI, 33.3-76.2; p = 0.799) and median progression-free survival of 7.4 months (95% CI, 4.43-10.38; p = 0.833) after crizotinib treatment. Interestingly, there were two patients responded to crizotinib had their ALK rearrangement detected by RT-PCR but not FISH. CONCLUSIONS: RT-PCR should be considered as an alternative/supplemental approach to detect ALK fusion oncogene in NSCLC patients who might benefit from crizotinib treatment. PMID- 26352534 TI - Survival After Sublobar Resection versus Lobectomy for Clinical Stage IA Lung Cancer: An Analysis from the National Cancer Data Base. AB - BACKGROUND: Recent data have suggested possible oncologic equivalence of sublobar resection with lobectomy for early-stage non-small-cell lung cancer (NSCLC). Our aim was to evaluate and compare short-term and long-term survival for these surgical approaches. METHODS: This retrospective cohort study utilized the National Cancer Data Base. Patients undergoing lobectomy, segmentectomy, or wedge resection for preoperative clinical T1A N0 NSCLC from 2003 to 2011 were identified. Overall survival (OS) and 30-day mortality were analyzed using multivariable Cox proportional hazards models, logistic regression models, and propensity score matching. Further analysis of survival stratified by tumor size, facility type, number of lymph nodes (LNs) examined, and surgical margins was performed. RESULTS: A total of 13,606 patients were identified. After propensity score matching, 987 patients remained in each group. Both segmentectomy and wedge resection were associated with significantly worse OS when compared with lobectomy (hazard ratio: 1.70 and 1.45, respectively, both p < 0.001), with no difference in 30-day mortality. Median OS for lobectomy, segmentectomy, and wedge resection were 100, 74, and 68 months, respectively (p < 0.001). Finally, sublobar resection was associated with increased likelihood of positive surgical margins, lower likelihood of having more than three LNs examined, and significantly lower rates of nodal upstaging. CONCLUSION: In this large national level, clinically diverse sample of clinical T1A NSCLC patients, wedge and segmental resections were shown to have significantly worse OS compared with lobectomy. Further patients undergoing sublobar resection were more likely to have inadequate lymphadenectomy and positive margins. Ongoing prospective study taking into account LN upstaging and margin status is still needed. PMID- 26352535 TI - Modified Corneosurfametry as a new accelerated high-throughput ex vivo methodology for predicting cleanser effects towards human skin. AB - BACKGROUND: Corneosurfametry (CSM) was originally developed as a tool to predict irritation potential of cleansers. In this method, surface skin stripped using cyanoacrylate is contacted with surfactants/products, rinsed and stained with toluidine blue and basic fuschin dyes. The intensity of staining increases with increases in irritation potential of surfactant. Our objective was to modify the CSM technique to achieve better control of the tape stripping process. Another objective was to correlate the modified CSM (MCSM) with a traditional in-vivo forearm controlled application test (FCAT) for mildness and to explore its utility to assess the state of corneum after a clinical test. METHODS: Surface skin cells were tape stripped from forearms of volunteers with D-Squame Adhesive Discs. Discs were treated with a 10% solution of the product in a 96-plate well for 10 min, rinsed, dried and treated with basic fuschin-toluidine blue dye solution, rinsed and dried again. Forearm Controlled Application Test (FCAT) was based on a published protocol. Tape strips obtained after product treatment were also analyzed by the MCSM procedure without additional product treatment. RESULTS: Mildness/barrier damage assessed from in-vivo FCAT showed a similar ranking to the MCSM results. MCSM, TEWL and Erythema analysis of between treatment differences showed a good correlation indicating that barrier damage seen in in-vivo studies can be predicted from ex-vivo MCSM studies. MCSM analysis of tape strips after the FCAT study showed that the damage decreased with increase in tape strip number. A moisturizing body wash (MBW) with mild surfactants showed the least damage in all layers. In contrast, harsh dish washing liquid showed significantly higher damage down to several layers. Another MBW with petrolatum in a harsher base showed damage almost similar to that of the harsh dish washing liquid in the surface layers. Thus, the MCSM was able to show underlying damage which would have been normally masked by the deposited petrolatum. CONCLUSION: The MCSM assay was shown to be a valuable tool for accelerated high throughput evaluation of mildness of surfactants and fully formulated products. MCSM can also be used to assess the state of the corneum after a product treatment. PMID- 26352536 TI - A kinematic and metabolic analysis of the first Lu of Tai Chi in experts and beginners. AB - The aim of this study was to compare movement kinematics, cocontraction times, and metabolic data in expert and nonexpert Tai Chi practitioners. Significant differences were observed for all kinematic parameters: experts moved smoothly (lower jerk) and with a lower frequency. No differences in metabolic and electromyography data were observed but for the breathing pattern (experts breathed slowly and deeply). Movement frequency and breathing pattern are thus the main features that distinguish expert and nonexpert practitioners. PMID- 26352537 TI - Lithium chloride attenuates the abnormal osteogenic/adipogenic differentiation of bone marrow-derived mesenchymal stem cells obtained from rats with steroid related osteonecrosis by activating the beta-catenin pathway. AB - Steroid-related osteonecrosis of the femoral head (ONFH) may be a disease that results from the abnormal osteogenic/adipogenic differentiation of bone marrow derived mesenchymal stem cells (BMMSCs). In the present study, we examined the possible use of lithium in an aim to reverse the abnormal osteogenic/adipogenic differentiation of BMMSCs isolated from rats with steroid-related ONFH (termed ONFH-BMMSCs). BMMSCs obtained from steroid-related ONFH rat femurs were cultured with or without lithium chloride (LiCl). BMMSCs obtained from normal rat femurs were cultured as controls. LiCl significantly increased the expression of osteocalcin and Runx2 in the ONFH-BMMSCs during osteogenic induction. The mineralization of ONFH-BMMSCs following osteogenic induction was also enhanced. Furthermore, LiCl exerted anti-adipogenic effects on the ONFH-BMMSCs by inhibiting the expression of peroxisome proliferator-activated receptor gamma (PPARgamma) and fatty acid binding protein 4 (Fabp4) during adipogenic induction, and decreasing lipid droplet formation at the end of adipogenic induction. These effects of LiCl on the ONFH-BMMSCs were associated with an increased expression of beta-catenin and a decreased expression of phosphorylated GSK-3beta at Tyr 216, and these effects were abolished by treatment with quercetin, an antagonist of the beta-catenin pathway. The normal osteogenic/adipogenic activity of BMMSCs may be impaired in steroid-related ONFH. However, as demonstrated by our findings, LiCl reduces abnormal adipogenic activity and simultaneously increases the osteogenic differentiation of ONFH-BMMSCs by activating the beta-catenin pathway. PMID- 26352538 TI - Removal or Revision of Vaginal Mesh Used for the Treatment of Stress Urinary Incontinence. AB - IMPORTANCE: Synthetic mesh slings are the most common surgical treatment for female stress urinary incontinence (SUI). However, the US Food and Drug Administration has released warnings that question the safety of vaginal mesh. OBJECTIVES: To measure the incidence of mesh removal or revision after SUI procedures and to determine whether significant surgeon and patient risk factors exist. DESIGN, SETTING, AND PARTICIPANTS: Population-based retrospective cohort study that included all adult women undergoing an incident procedure for SUI with synthetic mesh in Ontario, Canada, from April 1, 2002, through December 31, 2012 (N = 59 887). The end of potential follow-up was March 31, 2013. Data were analyzed from November 1, 2014, through February 28, 2015. EXPOSURES: Yearly volume of mesh-based procedures for SUI performed by the treating surgeons and their surgical specialty. MAIN OUTCOMES AND MEASURES: The primary outcome was a composite of surgical procedures related to removal or revision of mesh slings (owing to erosion, fistula, pain, or retention). We hypothesized a priori that surgeon volume would be inversely correlated with complications. RESULTS: Among the identified 59 887 women who underwent a mesh-based procedure for SUI, the median age was 52 (interquartile range [IQR], 45-63) years. High-volume surgeons (>=75th percentile of yearly mesh-based procedures) were less likely to perform a simultaneous hysterectomy (performed in 11.5% vs 16.5% of patients; standardized difference, 0.14), were more likely to work in an academic center (28.9% vs 16.3% of patients; standardized difference, 0.30), and saw the patient less frequently in the year before the procedure (median, 2 [IQR, 1-3] vs 3 [IQR, 2-4] visits; standardized difference, 0.26). Complications were treated in 1307 women (2.2%), and the 10-year cumulative incidence rate was 3.29 (95% CI, 3.05-3.53). In our multivariable survival model, patients of high-volume surgeons had a significantly lower risk (95% CI) for experiencing our composite outcome (hazard ratio [HR], 0.73 [0.65-0.83]; absolute risk reduction, 0.63% [0.36%-0.92%]; P < .01). Gynecologists were not significantly associated with more complications compared with urologists (HR, 0.94 [95% CI, 0.83-1.08]; P = .38). Among our secondary exposures of interest, multiple mesh-based SUI procedures increased the risk for complications (HR, 4.73 [95% CI, 3.62-6.17]; P < .01). However, traditional high-risk patient features did not increase the risk (HR, 0.58 [95% CI, 0.08-4.13]; P = .59). CONCLUSIONS AND RELEVANCE: Ten years after SUI mesh surgery, 1 of every 30 women may require a second procedure for mesh removal or revision. Patients of lower-volume surgeons have a 37% increased likelihood of having a complication. These findings support the recommendations of the US Food and Drug Administration related to the use of vaginal mesh for treatment of SUI. PMID- 26352539 TI - Recent developments and future challenges in immune checkpoint inhibitory cancer treatment. AB - PURPOSE OF REVIEW: In this review, we focus on the recent findings and future challenges in cancer treatment with immune checkpoint inhibitors. RECENT FINDINGS: Major progress has been made in recent years as the first immune checkpoint inhibitors are approved by the US Food and Drug Administration for the treatment of cancer patients. Anticytotoxic T-lymphocyte-associated protein 4 and antiprogrammed death protein 1/programmed death-ligand 1 (PD-L1) monoclonal antibodies are being extensively studied in many different tumor types, often showing impressive response rates, but also a typical serious toxicity profile in the form of auto-immunity. Unfortunately, it is not yet possible to prevent or predict these immune-related adverse events. Studies on mutational load, neo epitopes, lactate dehydrogenase, PD-L1 expression, and T-cell infiltration suggest that these markers are correlating with efficacy, but have not yet reached the status of a validated biomarker for checkpoint inhibitors. Other immune checkpoints are being investigated and new checkpoint inhibitors are on the brink of being evaluated in clinical trials. SUMMARY: The main challenge for the near future will be to predict efficacy of immune checkpoint blockade and to predict and prevent immune-related adverse events. More research should be done in order to find potential biomarkers that predict treatment response and/or toxicity; the optimal administration route, dosage, and frequency; and possible combinations of therapies that have an added or synergetic effect. PMID- 26352540 TI - State-of-the-art of bone marrow imaging in multiple myeloma. AB - PURPOSE OF REVIEW: Multiple myeloma is a common hematological malignancy arising in the bone marrow. Bone lesions were initially depicted with conventional radiography, although recently F-FDG PET/CT and MRI are recognized as having a clear role in the initial workup and in the evaluation of therapy response. RECENT FINDINGS: Tumor development produces osteolysis and expansive lesions. Although tumor burden and extent are key prognostic factors, different cancer hallmarks can also be evaluated in vivo through noninvasive imaging. SUMMARY: This imaging-based virtual biopsy approach might be useful to define several relevant prognostic markers, such as angiogenesis, cellularity, metabolic trapping and bone morphology and elasticity, both before and during treatment, to predict tumor behavior and the early effect of therapy. PMID- 26352541 TI - Epigenetic therapy of myelodysplastic syndromes and acute myeloid leukemia. AB - PURPOSE OF REVIEW: This review will discuss issues arising along with the expanding use of hypomethylating treatment (HMT) in the management of acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS). RECENT FINDINGS: HMT has been shown to induce responses in MDS and AML, and azacitidine (Vidaza, Celgene) has been shown to prolong survival in higher-risk MDS. Recent studies have supported the idea that disease stability may also be a treatment goal, whereas treatment interruption in responding patients is associated with rapid disease relapse and death. In AML, a modest but significant survival advantage has been shown for HMT by censoring patients at the time of subsequent AML therapy, but the major limitation remains the short duration of responses. Unfortunately, some of the strategies to overcome these limitations have failed, including the combination of HMT to histone-deacetylase inhibitors, which has not definitively shown to significantly prolong survival. Molecules interfering with other pathways impacting the survival and proliferation of blasts, used alone or in combination, including guadecitabine, selinexor, or inhibitors of IDH2 mutations, are more promising approaches. SUMMARY: Hypomethylating drugs are the first successful treatment for elderly patients with higher-risk MDS and are effective for some AML subtypes. Translational studies will hopefully identify patients with a favorable profile of response to these drugs, and help to identify newer targets for combination treatments. PMID- 26352542 TI - The genomic landscape of myeloid neoplasms with myelodysplasia and its clinical implications. AB - PURPOSE OF REVIEW: This article will review the most recent advances in the understanding of the genetic basis of myeloid neoplasms with myelodysplasia and will discuss its clinical implications. RECENT FINDINGS: Recurrent somatic mutations have been identified in about 90% of patients with myeloid neoplasms with myelodysplasia, involving genes of RNA splicing, DNA methylation, histone modification, transcription regulation, DNA repair, signal transduction, and cohesin complex. Somatic mutations are acquired in a linear manner in a multipotent hematopoietic stem cell, resulting in a growth advantage at the stem cell level and in defective differentiation and maturation of hematopoietic precursors. Recently, evidence has been provided of age-related hematopoietic clones, driven by mutations of genes recurrently mutated in myeloid neoplasms. These hematopoietic clones may represent either premalignant clones with the potential to progress to myeloid neoplasm or small malignant clones at a preclinical stage. SUMMARY: The available evidence clearly indicates that greater understanding of the molecular basis of myeloid neoplasms with myelodysplasia has relevant implications in the classification of these disorders, as well as in predicting disease risk and response to specific treatment modalities, and may open avenues of research leading to novel therapeutic options and personalized treatment in the individual patient. PMID- 26352544 TI - Heart Rate Variability in the Prediction of Risk for Posttraumatic Stress Disorder. PMID- 26352545 TI - EMMPRIN (CD147) Expression in Smooth Muscle Tumors of the Uterus. AB - Smooth muscle tumors of the uterus are the most common mesenchymal tumors of the gynecologic tract. The vast majority of these are benign leiomyomas that present no diagnostic difficulty. Because some benign smooth muscle tumors may degenerate and uncommon variants exist, the diagnosis can be challenging in some cases. The goal of this research was to investigate EMMPRIN expression in leiomyomas, leiomyoma variants, and leiomyosarcomas (LMS) to determine whether it has a potential role in differential diagnosis. EMMPRIN expression was investigated with immunohistochemistry in 103 uterine smooth muscle tumors, which included 19 usual leiomyomas, 52 leiomyoma variants, and 32 LMS. They were evaluated on the basis of staining extent, intensity, and also their combined score, and the groups were compared. EMMPRIN expression was present in 3 of 19 (15.7%) usual leiomyomas, 23 of 52 (44.3%) leiomyoma variants, and 28 of 32 (87.5%) LMS. There were statistically significant differences in staining extent and intensity, and also for their combined scores, between the LMS and benign groups. Although uterine smooth muscle tumors are usually diagnosed easily with conventional diagnostic criteria, the differentiation of LMS from some variants of leiomyoma can be challenging based soley on morphology. EMMPRIN may be a valuable immunohistochemical marker for differentiating LMS from benign smooth muscle tumors in problematic cases. PMID- 26352546 TI - FIGO Stage III Metastatic Gestational Choriocarcinoma Developed From an Antecedent Partial Hydatidiform Molar Pregnancy Bearing a Numerical Chromosomal Aberration 68, XX: A Case Report and Literature Review. AB - A 36-yr-old, gravida 5 para 4 woman presented with uterine bleeding and was discovered to have a 3.7-cm uterine mass with multiple, bilateral, lung metastases. Six months earlier, the patient was diagnosed with a partial hydatidiform mole that demonstrated a rare chromosomal karyotype 68, XX[12]. The patient's serum beta-human chorionic gonadotropin was elevated from baseline to 12,039 mIU/mL before the treatment. A total hysterectomy was performed and revealed a markedly hemorrhagic, extensively necrotic choriocarcinoma. The tumor mass invaded to a depth of 1/3 of the uterine wall thickness. Cytogenetic analysis of the choriocarcinoma revealed the same 68, XX karyotype, as observed in the antecedent partial hydatidiform mole. A clinical diagnosis of advanced stage invasive choriocarcinoma was rendered, with a risk factor score of 5. Following the development of chemoresistance to a single-agent (methotrexate) regimen, the patient subsequently received 5 cycles of chemotherapy (EMA-CO), without any major complication. She is currently >5 yr posttreatment and is asymptomatic. Her most recent imaging studies, including scans of chest and brain, show no evidence of disease, and her serum beta-human chorionic gonadotropin level has remained consistently below detectable levels. PMID- 26352543 TI - Smart CARs engineered for cancer immunotherapy. AB - PURPOSE OF REVIEW: Chimeric antigen receptors (CARs) are synthetic immunoreceptors, which can redirect T cells to selectively kill tumor cells, and as 'living drugs' have the potential to generate long-term antitumor immunity. Given their recent clinical successes for the treatment of refractory B-cell malignancies, there is a strong push toward advancing this immunotherapy to other hematological diseases and solid cancers. Here, we summarize the current state of the field, highlighting key variables for the optimal application of CAR T cells for cancer immunotherapy. RECENT FINDINGS: Advances in CAR T-cell therapy have highlighted intrinsic CAR design and T-cell manufacturing methods as critical components for maximal therapeutic success. Similarly, addressing the unique extrinsic challenges of each tumor type, including overcoming the immunosuppressive tumor microenvironment and tumor heterogeneity, and mitigating potential toxicity, will dominate the next wave of CAR T-cell development. SUMMARY: CAR T-cell therapeutic optimization, including intrinsic and extrinsic factors, is critical to developing effective CAR T-cell therapies for cancer. The excitement of CAR T-cell immunotherapy has just begun, and will continue with new insights revealed in laboratory research and in ongoing clinical investigations. PMID- 26352547 TI - Prostate-Type Adenocarcinoma in Mature Cystic Ovarian Teratoma. AB - We report our experience with prostatic-type tissue in ovarian teratomas, and in particular we highlight a case of prostatic-type adenocarcinoma arising within a mature cystic ovarian teratoma in a 32-yr-old woman. On gross examination, the cyst consisted of typical features of a dermoid cyst. Closer examination revealed a single 1.5-cm solid nodule within the cyst. Microscopically, it was composed of a small cyst-like structure lined by urothelium and to one side glandular and stromal tissue consistent with prostate parenchyma. Within the prostatic-type tissue, there were malignant glands morphologically and immunohistochemically supportive of prostatic-type adenocarcinoma Gleason score 3+3=6. There were also areas consistent with high-grade prostatic intraepithelial neoplasia. Although there are several reports in the literature of benign prostatic-type tissue arising within ovarian as well as testicular teratomas, to our knowledge, prostatic-type adenocarcinoma arising in a mature ovarian teratoma is an extremely rare phenomenon, with only 1 previous report in the literature. PMID- 26352548 TI - Value of PAX-8 and SF-1 Immunohistochemistry in the Distinction Between Female Adnexal Tumor of Probable Wolffian Origin and its Mimics. AB - Female adnexal tumors of probable wolffian origin (FATWOs) are rare. They can closely mimic endometrioid adenocarcinomas with a prominent spindle cell component and Sertoli cell tumors (SCTs). To further define their immunohistochemical profile and origin, we investigated the expression of PAX-8, PAX-2, and GATA binding protein 3 (GATA-3) (wolffian markers) and of steroidogenic factor-1 (SF-1) (sex-cord stromal marker) in FATWOs. We also studied the expression of PAX-8 and PAX-2 in endometrioid adenocarcinomas; of SF 1 in Sertoli-Leydig cell and SCTs; and of PAX-8, PAX-2, GATA-3, and SF-1 in rete ovarii-a proposed site of origin for FATWOs. A database search yielded 8 FATWOs, 18 ovarian/tubal/paraovarian endometrioid adenocarcinomas, and 8 ovarian Sertoli Leydig cell and SCTs. Eleven cases with rete ovarii sections were included. Of the FATWOs studied, all were negative for PAX-8, PAX-2, GATA-3, and SF-1. Of the endometrioid adenocarcinomas studied, PAX-8 was positive in all and PAX-2 was positive in 57%. Of the Sertoli-Leydig cell and SCTs, all were positive for SF-1 except one. The rete ovarii were positive for PAX-8, weakly positive for SF-1, and negative for PAX-2 and GATA-3. Our study suggests that PAX-8 and SF-1 can be helpful in the distinction between FATWOs and endometrioid adenocarcinomas and SCTs, respectively. Our results do not support a Mullerian or sex-cord stromal or rete ovarii origin for FATWOs. It is curious, however, that FATWOs do not express wolffian markers-it is possibly related to their origin from a distinctive portion of the wolffian duct. PMID- 26352549 TI - Uterine Angiosarcoma: A Case Report and Literature Review. AB - Uterine angiosarcoma is a rare, extremely malignant vascular tumor. Here, we report a case of giant uterine angiosarcoma in a 56-yr-old woman. The tumor was diagnosed as an epithelioid uterine angiosarcoma based on histopathologic findings. The tumor cells showed vascular differentiation; they were positive for the vascular endothelial markers CD31, CD34, and was negative for lymphatic endothelial marker D2-40. In addition, the tumor cells showed overexpression of cell-cycle regulatory protein cyclin D1 and were positive for epithelial mesenchymal transition marker vimentin. Although it was reported previously that there was breakage in YWHAE, NUTM2A (FAM22A), and NUTM2B (FAM22B) in a case of uterine angiosarcoma, no breakage in these loci was detected by fluorescence in situ hybridization in the present case. PMID- 26352550 TI - An Expanded Spectrum of High-Grade B-Cell Non-Hodgkin Lymphomas Involving the Cervicovaginal Region. AB - The uterine cervix and vaginal regions are infrequently infiltrated by lymphoma. Involvement of these topographic regions may constitute primary disease or more commonly represent a manifestation of systemic lymphomatous disease. Herein, we report an expanded spectrum of high-grade B-cell non-Hodgkin lymphomas comprising plasmablastic lymphoma (with and without plasmacytic differentiation), ALK positive large B-cell lymphoma, and diffuse large B-cell lymphoma which involved the uterine cervix and/or vagina of 6 patients at initial diagnosis. These tumors clinically mimicked carcinoma and developed predominantly, but not exclusively, in the setting of human immunodeficiency virus infection. PMID- 26352551 TI - Application of p16 Immunohistochemistry and RNA In Situ Hybridization in the Classification of Adenoid Basal Tumors of the Cervix. AB - Our understanding of adenoid basal tumors of the cervix has evolved over time. Most of the proliferations referred to as adenoid basal carcinoma have a clinically benign course--leading some to suggest the term "adenoid basal epithelioma." However, rarely, these may be associated with invasive carcinomas. These tumors have been etiologically linked with high-risk human papillomavirus (HR-HPV) infection. Here, we investigate the use of p16 immunohistochemistry and HR-HPV RNA in situ hybridization (ISH) in the classification of adenoid basal tumors of the cervix. Seventeen cases of adenoid basal tumors of the cervix were included. The patients' age ranged from 19 to 79 yr (average, 59 yr). p16 immunostain was performed on all cases and RNA ISH was performed in 4 cases with available formalin-fixed paraffin-embedded tissue. There were 11 low-grade tumors, 5 frankly invasive carcinomas, and 1 with histologic features that were intermediate between the former 2 categories. p16 immunostain was negative or showed patchy cytoplasmic staining in the low-grade tumors and was strongly and diffusely positive in the invasive carcinomas. HR-HPV RNA ISH was negative in the 3 low-grade tumors and was positive in 1 case of invasive carcinoma including the adenoid basal component. Distinct p16 immunostaining and HR-HPV RNA ISH patterns exist between low-grade adenoid basal tumors and invasive adenoid basal carcinomas. Our study indicates that p16 immunostaining and HR-HPV RNA ISH can be employed as useful ancillary tools in differentiating between noninvasive and invasive adenoid basal tumors along with careful histopathologic evaluation. PMID- 26352552 TI - Adenocarcinoma With Breast/Adnexal and Upper Gastrointestinal Differentiation Arising in an Ovarian Mature Cystic Teratoma: A Case Report and Review of the Literature. AB - Mature cystic teratomas are the most common type of ovarian germ cell tumors. In about 1% of cases, usually among postmenopausal women, a mature cystic teratoma can undergo malignant transformation. Among malignant transformations, squamous cell carcinoma is the most common histology, comprising approximately 80% of cases. In this report, we present the unique case of a 55-yr-old woman with a pelvic mass found to be a mature cystic teratoma with malignant transformation to adenocarcinoma with breast/adnexal, upper gastrointestinal, and neuroendocrine differentiation. The predominant malignant component was the adenocarcinoma exhibiting breast/skin adnexal differentiation, which was found to involve the omentum and a right para-aortic node. We provide an in-depth review of the pathologic findings, as well as a review of the current literature on malignant transformation to adenocarcinoma. This report aims to open a conversation regarding the management of these patients, with a specific focus on the role of molecular analysis and targeted therapies. PMID- 26352553 TI - RETINAL PIGMENT EPITHELIUM UNDULATIONS IN ACUTE STAGE OF VOGT-KOYANAGI-HARADA DISEASE: Biomarker for Functional Outcomes After High-Dose Steroid Therapy. AB - PURPOSE: To determine the clinical significance of retinal pigment epithelium (RPE) undulations in the acute stage of Vogt-Koyanagi-Harada disease. METHODS: Retinal pigment epithelium undulations were detected and classified into 3 grades: Grade 1, slight; Grade 2, moderate; and Grade 3, severe undulations, in the enhanced depth imaging optical coherence tomographic images. The relationship between the clinical characteristics and the presence of RPE undulations was investigated. RESULTS: Among the 61 eyes of 31 patients with Vogt-Koyanagi-Harada disease, 40 eyes had some degree of RPE undulations (Grade 1 = 12, Grade 2 = 15, and Grade 3 = 13). The patients with RPE undulations in both eyes were significantly older at the onset (P = 0.0002). The eyes with RPE undulations were more likely to develop posterior recurrences (P = 0.032) and have worse vision at 12 months (P = 0.043). Multiple regression analysis revealed that RPE undulations were an independent predictor of posterior recurrences (P = 0.009) and poor visual outcomes (P = 0.035). CONCLUSION: Retinal pigment epithelium undulations detected by enhanced depth imaging optical coherence tomographic are relatively frequent occurrences at the acute stage of Vogt-Koyanagi-Harada, and their presence is a predictor of posterior recurrences and poor visual outcomes after high-dose steroid therapy. PMID- 26352554 TI - RESTORATION OF RETINALLY INDUCED ANISEIKONIA IN PATIENTS WITH EPIRETINAL MEMBRANE AFTER EARLY VITRECTOMY. AB - PURPOSE: To evaluate changes in aniseikonia in patients with unilateral epiretinal membrane after surgery. METHODS: This prospective study included 24 patients with unilateral idiopathic epiretinal membrane who underwent vitrectomy. Best-corrected visual acuity and aniseikonia were measured using the Aniseikonia Inspector 3 (Optical Diagnostics, Culemborg, The Netherlands) preoperatively and 6 months postoperatively. Aniseikonia was measured in vertical and horizontal directions. RESULTS: Mean age at surgery was 64.2 +/- 9.3 years, and mean symptom duration was 12.9 +/- 11.4 months. Mean changes in aniseikonia after surgery were 41.0 +/- 31.4% reduction in the vertical direction and 41.6 +/- 30.8% reduction in the horizontal direction (both P < 0.001). The remaining aniseikonia after surgery correlated with symptom duration (r = 0.565, P = 0.006, and r = 0.812, P < 0.001, for vertical and horizontal directions, respectively). The good preoperative best-corrected visual acuity group showed better improvement of aniseikonia than did the poor preoperative group (P = 0.046 and P = 0.025 for vertical and horizontal directions, respectively). CONCLUSION: Greater improvement of aniseikonia after epiretinal membrane peeling was achieved in patients with better preoperative best-corrected visual acuity and shorter symptom durations. Early vitrectomy helped to reduce aniseikonia in patients with epiretinal membrane. PMID- 26352555 TI - INTRAVITREAL CORTICOSTEROIDS IN DIABETIC MACULAR EDEMA: PHARMACOKINETIC CONSIDERATIONS. AB - PURPOSE: To review the relationship between kinetics, efficacy, and safety of several corticosteroid formulations for the treatment of diabetic macular edema. METHODS: Reports of corticosteroid use for the treatment of diabetic macular edema were identified by a literature search, which focused on the pharmacokinetics, efficacy, and safety of these agents in preclinical animal models and clinical trials. RESULTS: Available corticosteroids for diabetic macular edema treatment include intravitreal triamcinolone acetonide, dexamethasone, and fluocinolone acetonide. Because of differences in solubility and bioavailability, various delivery mechanisms are used. Bioerodible delivery systems achieve higher maximum concentrations than nonbioerodible formulations. There is a relationship between visual gains and drug persistence in the intravitreal compartment. Safety effects were more complex; level of intravitreal triamcinolone acetonide exposure is related to development of elevated intraocular pressure and cataract; this does not seem to be the case for dexamethasone, where two different doses showed similar mean intraocular pressure and incidence of cataract surgery. With fluocinolone acetonide, rates of intraocular pressure elevations requiring surgery seem to be dose related; rates of cataract extraction were similar regardless of dose. CONCLUSION: Available corticosteroids for diabetic macular edema exhibit different pharmacokinetic profiles that impact efficacy and adverse events and should be taken into account when developing individualized treatment plans. PMID- 26352556 TI - LONG-TERM OUTCOME OF EPIRETINAL MEMBRANE SURGERY IN YOUNG CHILDREN. AB - PURPOSE: To describe the clinical characteristics of epiretinal membranes (ERMs) secondary to nonprogressive diseases in very young children and to assess their surgical outcome. METHODS: Retrospective interventional case series study of 13 pediatric patients (aged less than 12 years) operated on for ERM more than a 6 year period. Visual acuity measurement, ophthalmic examination, and optical coherence tomography imaging were assessed preoperatively and postoperatively. RESULTS: Mean age was 6.5 years (3-12 years). Mean follow-up duration was of 28.5 months (12-69 months). Among the 13 patients, there were 7 cases of idiopathic ERM, 4 cases of combined hamartoma of the retina and retinal pigment epithelium, and 2 cases of posttraumatic ERM. The diagnosis of ERM was fortuitous in 10 cases (77%). Twelve children (92%) experienced a functional improvement. All patients received adjuvant treatment of amblyopia. Best-corrected visual acuity improved significantly after surgery from 20/160 to 20/40 (P = 0.001). CONCLUSION: Even in very young children, surgery resulted in a significant long-term improvement. Children screening was essential for diagnosis and treatment in most cases. PMID- 26352557 TI - RETINAL AND CHOROIDAL VASCULATURE IN BIRDSHOT CHORIORETINOPATHY ANALYZED USING SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY. AB - PURPOSE: To describe retinal and choroidal vascular changes in eyes with birdshot chorioretinopathy using optical coherence tomography angiography. METHODS: Patients underwent imaging using the AngioVue prototype software of the RTVue XR spectral domain optical coherence tomography device (Optovue, Inc) between September and December 2014. Two trained patients evaluated the optical coherence tomography angiography images for changes in the retinal and choroidal vasculature in the posterior pole. RESULTS: Four of eight eyes (50%) had birdshot lesions in the posterior pole as demonstrated on fundus photography. All of these eyes demonstrated the areas of decreased choroidal blood flow below the disrupted retinal pigment epithelium. Larger choroidal vessels bordered the birdshot lesions. All eyes analyzed showed retinal thinning, telangiectatic vessels, and an increased intercapillary space. Capillary dilatations and loops were each seen in 7 of 8 eyes (88%). CONCLUSION: Optical coherence tomography angiography provides precise microvascular detail of the retinal vasculature and choriocapillaris that allows for the noninvasive visualization of the birdshot lesions and changes in the inner retina. The optical coherence tomography angiography images delineated widespread retinal vascular findings not previously described in the literature. In the future, optical coherence tomography angiography could be a useful tool to evaluate the natural history of birdshot chorioretinopathy, its progression, and the effect of treatment in these patients. PMID- 26352558 TI - Reversible or not? Distinguishing agglomeration and aggregation at the nanoscale. AB - Nanoparticles are prone to clustering either via aggregation (irreversible) or agglomeration (reversible) processes. It is exceedingly difficult to distinguish the two via conventional techniques such as dynamic light scattering (DLS), nanoparticle tracking analysis (NTA), or electron microscopy imaging (scanning electron microscopy (SEM), transmission electron microscopy (TEM)) as such techniques only generally confirm the presence of large particle clusters. Herein we develop a joint approach to tackle the issue of distinguishing between nanoparticle aggregation vs agglomeration by characterizing a colloidal system of Ag NPs using DLS, NTA, SEM imaging and the electrochemical nanoimpacts technique. In contrast to the conventional techniques which all reveal the presence of large clusters of particles, electrochemical nanoimpacts provide information regarding individual nanoparticles in the solution phase and reveal the presence of small nanoparticles (<30 nm) even in high ionic strength (above 0.5 M KCl) and allow a more complete analysis. The detection of small nanoparticles in high ionic strength media evidence the clustering to be a reversible process. As a result it is concluded that agglomeration rather than irreversible aggregation takes place. This observation is of general importance for all colloids as it provides a feasible analysis technique for a wide range of systems with an ability to distinguish subtly different processes. PMID- 26352559 TI - Impact of D-index and L-index on pulmonary infection in induction chemotherapy for acute lymphoblastic leukemia and lymphoblastic lymphoma. AB - OBJECTIVES: The D-index and the L-index, calculated as the area over the neutrophil and lymphocyte curves, respectively, reflect both the intensity and duration of cytopenia. We, retrospectively, investigated the impact of these indexes on pulmonary infection (PI) in induction chemotherapy for acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL). METHODS: We included 92 patients (ALL 83, LBL 9) from two institutions. We calculated the D index and cumulative D-index until the development of PI (c-D-index), which enables real-time risk assessment for infection. We also calculated the L-index (35), defined as the area over the lymphocyte curve during lymphopenia (<700/ul) until day 35 and the cumulative-L-index until the development of PI (c-L-index). RESULTS: Eight patients developed PI on day 20 (median). Two patients were strongly suspected to have bacterial pneumonia, and the others were suspected to have pulmonary fungal infection. The D-index and the L-index (35) in patients with PI were higher than those in patients without PI (7230 +/- 4734 vs. 4519 +/- 3416, P = 0.041 and 15 458 +/- 5243 vs. 8920 +/- 5901, P = 0.018), while the c-D index and the c-L-index were not significantly different. Although the c-L-index did not have predictive value for PI, c-D-index, when treated as a dichotomous variable with a cutoff value of 5589 as determined by a receiver operating characteristic curve analysis, showed a significant difference between two groups (P = 0.045). This association became clearer when we focused on suspected pulmonary fungal infection. DISCUSSION AND CONCLUSION: In induction chemotherapy for ALL/LBL, c-D-index with a cutoff value of 5589 might have predictive value for the development of PI. PMID- 26352560 TI - Supine versus Prone Position during Extracorporeal Shockwave Lithotripsy for Treating Distal Ureteral Calculi: A Systematic Review and Meta-Analysis. AB - PURPOSE: We aimed at evaluating the efficacy of extracorporeal shockwave lithotripsy (SWL) for treating distal ureteral calculi performed in supine vs. prone position. MATERIALS AND METHODS: Eligible studies were identified by 2 reviewers using PubMed, Embase, and Web of Science databases. Outcomes included stone-free rate after the first and the final SWL session, the mean number of shocks per SWL session, the mean percentage of power used in the first SWL session, and the mean number of SWL sessions per patient. RESULTS: Pooled data among the 647 included patients showed that supine SWL was associated with a significantly higher stone-free rate than prone SWL. This difference was consistent for both the first SWL session (OR 4.17; 95% CI 2.53-6.87; p < 0.00001) and the final session (OR 3.02; 95% CI 1.96-4.67; p < 0.00001). No differences in the mean number of shocks per SWL session, the mean percentage of power used in the first SWL session, and the mean number of SWL sessions per patient were observed between the positions. SWL complications were infrequent and the incidence was insufficient for further analysis. CONCLUSION: SWL is safe and effective for the management of distal ureteral calculi, and supine SWL is more effective than prone SWL for achieving a stone-free status. PMID- 26352561 TI - Femtosecond Laser-assisted Arcuate Keratotomy Versus Toric IOL Implantation for Correcting Astigmatism. AB - PURPOSE: To evaluate the clinical efficacy and safety of femtosecond laser assisted arcuate keratotomy (FS-AK) versus toric intraocular lens (IOL) implantation for correcting astigmatism in patients with cataract. METHODS: A retrospective chart review was performed. All patients had senile cataracts with corneal astigmatism (range: +1.00 to +3.00 diopters [D]) before cataract surgery. Twenty-five patients agreed to undergo toric IOL implantation (the toric IOL group). Twenty-three patients did not agree to undergo toric IOL implantation despite astigmatism; however, these patients were not satisfied with their remaining astigmatism following cataract surgery and requested astigmatism correction using FS-AK (the FS-AK group). Visual acuity and intraocular pressure were evaluated, and automated refraction, keratometry, and slit-lamp examinations were performed at 1 day, 1 week, 1 month, and 5 months after surgery. RESULTS: Refractive astigmatism decreased in both groups. The mean preoperative and postoperative refractive cylinders were 1.71 +/- 1.15 and 0.78 +/- 1.06 D, respectively, in the FS-AK group (P < .001) and 1.67 +/- 0.13 and 0.83 +/- 0.097 D, respectively, in the toric IOL group (P < .001). There were no statistically significant differences between groups at any time during the follow-up period. CONCLUSIONS: FS-AK is a fast, customizable, adjustable, precise, and safe procedure for reducing refractive errors in patients with residual astigmatism after cataract surgery. The results of this procedure are comparable to the toric IOL. PMID- 26352562 TI - SMILE Procedures With Four Different Cap Thicknesses for the Correction of Myopia and Myopic Astigmatism. AB - PURPOSE: To study the feasibility of performing myopic femtosecond small incision lenticule extraction (SMILE) with four different cap thicknesses (130, 140, 150, and 160 MUm). METHODS: In this retrospective, comparative, non-randomized clinical trial, a refractive lenticule of intrastromal corneal tissue was cut with the VisuMax femtosecond laser system (Carl Zeiss Meditec AG, Jena, Germany) using different depths of the non-refractive lenticule cut. Manifest refraction, uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), and Objective Scattering Index (OSI) were evaluated. Minimum follow-up time was 1 year. RESULTS: Ninety-four eyes of 47 patients with myopia with (14 patients) and without (33 patients) astigmatism were treated. One year after the surgery, mean log-MAR UDVA, logMAR CDVA, SE, and OSI were 0.07 +/- 0.12, 0.01 +/- 0.37, 0.07 +/- 0.57, and 0.88 +/- 0.17, respectively (P < .05). There were no significant statistical differences in logMAR UDVA, logMAR CDVA, SE, or OSI (P > .05) variables when the different groups were compared for the same periods of time. CONCLUSIONS: No differences in visual acuity, refractive outcomes in optical visual quality, or complications were observed when using SMILE at four different depths. PMID- 26352563 TI - Optical Zone Centration Accuracy Using Corneal Fixation-based SMILE Compared to Eye Tracker-based Femtosecond Laser-assisted LASIK for Myopia. AB - PURPOSE: To compare the optical zone centration accuracy between myopic eyes treated with small incision lenticule extraction (SMILE) and LASIK. METHODS: Retrospective analysis of 100 consecutive eyes treated with SMILE (the SMILE group) with the corneal fixation-based centration VisuMax femtosecond laser (Carl Zeiss Meditec, Jena, Germany) and a matched group of 100 eyes treated with LASIK (the LASIK group) with VisuMax flap creation and eye tracker-based centration MEL 90 excimer laser (Carl Zeiss Meditec) ablation. In SMILE, the corneal vertex of the coaxially fixating eye was aligned with the vertex of the curved contact glass. In LASIK, the treatment was centered on the coaxially sighted corneal light reflex (first Purkinje image). A tangential (instantaneous) curvature preoperative to postoperative difference map was generated for each eye. A fixed grid and set of concentric circles were superimposed on the difference map to measure the offset between the optical zone center and corneal vertex (0,0), and vector analysis was used for comparative analysis at 3 months postoperatively. RESULTS: Mean centration offset was 0.20 +/- 0.11 mm for the SMILE group and 0.17 +/- 0.10 mm for the LASIK group, with no statistically significant difference between groups (P >.05). In the SMILE group, the optical zone was centered within 0.1 mm of the corneal vertex in 17% of eyes, within 0.2 mm in 55% of eyes, within 0.3 mm in 81% of eyes, and within 0.4 mm in 96% of eyes. In the LASIK group, the optical zone was centered within 0.1 mm of the corneal vertex in 24% of eyes, within 0.2 mm in 62% of eyes, within 0.3 mm in 92% of eyes, and within 0.4 mm in 98% of eyes. There was no systematic directional decentration in either group. CONCLUSION: Optical zone centration accuracy was no different between SMILE and LASIK with the MEL 90 laser. PMID- 26352564 TI - Fellow Eye Comparison of Nerve Fiber Regeneration After SMILE and Femtosecond Laser-assisted LASIK: A Confocal Microscopy Study. AB - PURPOSE: To compare postoperative corneal nerve fiber regeneration after small incision lenticule extraction (SMILE) and femtosecond laser-assisted LASIK (FS LASIK). METHODS: The medical records of patients who underwent SMILE were retrospectively reviewed. Patients with SMILE in one eye (the SMILE group) and FS LASIK in the fellow eye (the FS-LASIK group) and who had undergone a confocal microscopy study were retrospectively identified. Subbasal nerve fiber density was measured and compared between the groups preoperatively and at 1 week and 1, 3, and 6 months postoperatively. RESULTS: Thirty eyes of 15 patients were included in the study. Preoperative characteristics of the eyes were similar between the groups. However, there was a statistically significant difference in subbasal nerve fiber density between the groups at 1 month (SMILE group: 1,505 +/ 627 um/mm(2) [range: 625 to 2,540 um/mm(2)], FS-LASIK group: 1,107 +/- 509 um/mm(2) [range: 595 to 2,313 um/mm(2)], P = .003) and 3 months (SMILE group: 1,534 +/- 503 um/mm(2) [range: 650 to 2,255 um/mm(2)], FS-LASIK group: 1,194 +/- 485 um/mm(2) [range: 530 to 1,695 um/mm(2)], P = .004) postoperatively. No statistically significant difference was detected at 1 week and 6 months postoperatively. CONCLUSION: Eyes treated with SMILE have a higher density of subbasal nerve fibers than eyes treated with FS-LASIK in the early postoperative period (1 week to 3 months) but the two procedures are equivalent by 6 months postoperatively. PMID- 26352565 TI - Femtosecond Laser-assisted Wavefront-guided LASIK Using a Newer Generation Aberrometer: 1-Year Results. AB - PURPOSE: To evaluate long-term outcomes of wavefront-guided LASIK with a new advanced aberrometer. METHODS: Fifty eyes of 25 LASIK candidates with myopia and/or astigmatism underwent aberrometry (iDesign Advanced WaveScan; Abbott Medical Optics, Santa Ana, CA), femtosecond laser-assisted flap creation, and excimer ablation. Uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), spherical equivalent (SEQ), and astigmatism outcomes were measured at 1, 3, 6, and 12 months postoperatively. RESULTS: The sphere, cylinder, and SEQ were -4.29 +/- 1.94, -0.75 +/- 0.76, and -4.67 +/- 2.01 diopters (D), respectively, preoperatively and 0.03 +/- 0.13, -0.09 +/- 0.13, and -0.02 +/- 0.14 D, respectively, 12 months postoperatively (P < .001). The postoperative log-MAR CDVA (-0.07 +/- 0.09) and UDVA (-0.04 +/- 0.09) were better than the preoperative logMAR CDVA (0.07 +/- 0.10) (P < .01). Ninety-four percent achieved a 12-month logMAR UDVA of 0.0 or less (20/20 or better Snellen) and 100% achieved 0.3 or less (20/40 or better Snellen), compared to a preoperative logMAR CDVA of 0.0 or worse in 54% and 0.3 or less in 100%. Postoperative SEQ was within +/-0.50 D in 98%. The regression plot for achieved (y) vs intended (x) correction at 12 months was (y = 0.98 * - 0.09, R(2) = 0.99, P < .001). No cases lost CDVA. The target and 12-month surgically induced astigmatisms (TIA and SIA) were 0.91 +/- 0.75 and 0.82 +/- 0.70, respectively. The regression plot between them was SIA = 0.91 * TIA - 0.01 (R(2) = 0.95, P < .001). The angle of error was -0.29 degrees +/- 12.6 degrees and index of success was 0.13 +/- 0.25. There was only a mild, nonsignificant increase of higher-order aberrations after surgery, and the postoperative wavefront was stable on follow-up. CONCLUSIONS: Wavefront guided LASIK with iDesign aberrometry appears to be safe and effective in this long-term, consecutive case series. PMID- 26352566 TI - Opaque Bubble Layer Risk Factors in Femtosecond Laser-assisted LASIK. AB - PURPOSE: To determine the characteristics and risk factors for occurrence of opaque bubble layer (OBL) during femtosecond laser-assisted flap creation for LASIK. METHODS: One hundred ninety-eight eyes of 102 consecutive patients who underwent LASIK flap creation performed with the Alcon WaveLight FS200 laser (Alcon Laboratories, Inc., Fort Worth, TX) were retrospectively analyzed in a cohort study. Preoperative manifest refraction, corneal keratometry, central corneal thickness, white-to-white corneal diameter, corneal hysteresis, corneal resistance factor, and programmed flaps parameters were collected. Digital images automatically recorded after flap creation were analyzed to measure OBL areas. Correlation tests were performed between preoperative corneal parameters and OBL areas. RESULTS: The incidence rate of OBL was 48% (103 eyes). The mean OBL area as a percentage of the corneal flap area in the OBL group was 4.25% +/- 7.16% (range: 0% to 32.9%). The central corneal thickness, corneal resistance factor, and corneal hysteresis were significantly positively correlated with the OBL area (r = 0.242, P = .001; r = 0.254, P = .028; and r = 0.351, P < .0001, respectively). Corneal hysteresis and OBL area were positively correlated, independently of the central corneal thickness and other confounder factors with standardized coefficient (r = 0.353 +/- 0.227, P = .002). CONCLUSIONS: This study confirms the already known OBL risk factors with a larger cohort and suggests for the first time that an elevated corneal hysteresis is an independent predictive risk for OBL occurrence. PMID- 26352567 TI - Changes in Corneal Transparency After Cross-linking for Progressive Keratoconus: Long-term Follow-up. AB - PURPOSE: To determine long-term changes in corneal transparency after riboflavin ultraviolet A-induced corneal collagen cross-linking (CXL). METHODS: Charts and anterior segment data of patients after CXL for progressive keratoconus were retrospectively reviewed. Patients were examined using the Scheimpflug-based Pentacam corneal densitometry module (Oculus Optikgerate, Wetzlar, Germany) before CXL and at five postoperative follow-up visits: 1 to 3, 3 to 6, 6 to 12, 12 to 24, and 24 to 36 months. RESULTS: Forty-two eyes of 28 patients (mean age: 27.9 +/- 8.6 years) were included. Total corneal light backscatter was higher 1 to 3 months after CXL than before CXL (P < .001). There were significant differences, especially in the anterior (P < .001) and central (P < .001) layer at total diameter and posterior layer (P = .014) and the three central annuli at total corneal thickness (0 to 2 mm: P < .001; 2 to 6 mm: P < .001; 6 to 10 mm: P = .002). Total corneal light backscatter at total corneal thickness and total diameter faded over time following CXL. The backscatter was significantly lower 24 to 36 months after CXL than before CXL (P < .001). CONCLUSIONS: Corneal densitometry peaks in the first months after CXL and returns to preoperative values approximately 1 year after CXL. Two years after CXL, corneal densitometry reaches values obtained for healthy, untreated corneas, thus achieving an improvement in corneal clarity over untreated keratoconic corneas. PMID- 26352568 TI - In Vivo Confocal Microscopic Imaging of the Cornea After Femtosecond and Excimer Laser-assisted Penetrating Keratoplasty. AB - PURPOSE: To examine the microstructure of the cornea after excimer and femtosecond laser-assisted penetrating keratoplasty (ELAK and FLAK) in eyes with Fuchs' dystrophy and keratoconus. METHODS: Fifty-seven patients were divided into four groups according to corneal disease and surgical technique: Fuchs' dystrophy and ELAK (n = 9; mean age: 70.4 +/- 10.6 years); Fuchs' dystrophy and FLAK (n = 13; mean age: 64.3 +/- 11.2 years); keratoconus and ELAK (n = 9; mean age: 47.4 +/- 13.9 years); and keratoconus and FLAK (n = 9; mean age: 43.5 +/- 13.8 years). The control group comprised individuals without ocular disease (n = 17; mean age: 39.9 +/- 17.3 years). In vivo investigation of the corneal graft and graft-host junction zone was performed with confocal corneal microscopy. RESULTS: All corneal grafts were transparent and no rejection reaction could be observed during the follow-up period. Confocal microscopy revealed no difference in basal epithelial cell density compared to controls. Anterior keratocyte density was lower than in the control group (818 +/- 131 cells/mm(2)) in all four treatment groups (596 +/- 174, 586 +/- 113, 529 +/- 75, 552 +/- 91 cells/mm(2)). Langerhans cells could barely be seen; there was no difference in the cutting edge configuration and wound integrity. CONCLUSIONS: In vivo confocal microscopy provided evidence that good alignment of graft-host junction could be created with both techniques. The excimer laser was not inferior to the femtosecond laser in performing corneal cuts. The low density of Langerhans cells revealed well controlled cellular immunological response and sustained corneal integrity in both laser groups. PMID- 26352569 TI - Objective Evaluation of Planned Versus Achieved Stromal Thickness Reduction in Myopic Femtosecond Laser-assisted LASIK. AB - PURPOSE: To evaluate corneal stromal thickness reduction and compare to attempted and achieved ablation depth in a consecutive case series study of myopic LASIK. METHODS: Stromal thickness reduction was retrospectively evaluated in 205 consecutive eyes of 205 patients undergoing myopic and myopic astigmatic LASIK. Anterior segment optical coherence tomography was performed preoperatively and 3 months postoperatively. Epithelial thickness remodeling was also accounted for to achieve objective stromal thickness reduction. The derived maximum stromal thickness reduction was then compared to the programmed (planned) maximum ablation depth. Deviation of planned versus achieved maximum stromal thickness changes was correlated with residual refractive error. RESULTS: The 3-month stromal reduction was 86.01 +/- 28.28 um, compared to the average programmed maximum ablation depth of 88.48 +/- 26.05 um. The attempted versus achieved thickness outliers correlated with deviations in achieved refractive correction. CONCLUSIONS: Actual objective stromal thickness reduction following myopic LASIK correlates well with the attempted versus achieved refractive change. PMID- 26352570 TI - Small Incision Lenticule Extraction After Deep Anterior Lamellar Keratoplasty. AB - PURPOSE: Femtosecond laser-assisted small incision lenticule extraction (SMILE) was performed to correct myopic astigmatism in a 39-year-old patient who had previously undergone deep anterior lamellar keratoplasty (DALK) for keratoconus, with clinically significant anisometropia and contact lens intolerance. METHODS: Case report. RESULTS: SMILE was planned in the right eye to reduce the refractive error and to allow spectacle correction. The surgical procedure was centered on the visual axis, a 5.20-mm optical zone was used, and the refractive lenticule was extracted through a 3.25-mm incision located inside the graft edge. The refractive target was achieved 1 week after surgery and remained stable until the 3-month follow-up visit, while the corrected distance visual acuity improved from 20/100 to 20/40. Complications were not observed and the graft remained clear. In vivo confocal microscopy and anterior segment optical coherence tomography highlighted a regular wound healing and refractive interface profile. CONCLUSIONS: This case report highlights the feasibility of using SMILE as an alternative procedure for correcting refractive errors after keratoplasty, but further prospective studies are needed to prove the long-term refractive outcomes and safety of this technique. PMID- 26352571 TI - Uneventful Femtosecond Laser-assisted Flap Creation in a Patient With Postoperative PRK Corneal Haze. PMID- 26352572 TI - Surgically Induced Astigmatism Assessment. PMID- 26352573 TI - Salmon Protamine Decreases Serum and Liver Lipid Contents by Inhibiting Lipid Absorption in an In Vitro Gastrointestinal Digestion Model and in Rats. AB - Protamine has been used as an antiheparin drug and a natural preservative in various food products. However, limited studies have evaluated the physicochemical and functional properties of protamine. Hence, we assessed the mechanisms underlying the inhibition of lipid absorption following salmon protamine intake in in vitro and in vivo studies. In initial experiments, a salmon protamine hydrolyzate (PH) was prepared using in vitro simulated gastrointestinal digestion suppressed pancreatic lipase activity and micellar cholesterol solubility. This PH had higher bile acid-binding capacity and emulsion breakdown activity than casein hydrolyzate and l-arginine. However, the hypolipidemic functions of protamine were dramatically reduced by pancreatin digestion. In further experiments, groups of male Wistar rats were fed an AIN-93G diet containing 5% (wt/wt) salmon protamine or a protamine amino acid mixture. After 4 wk of feeding with experimental diets, reductions in serum and liver triacylglycerol (TAG) and cholesterol contents were observed in the presence of protamine, reflecting inhibition of TAG, cholesterol, and bile acid absorption. These data suggest that the formation of insoluble PH-bile acid complexes is critical before the bile acid-binding capacity is reduced. Therefore, dietary salmon protamine may ameliorate lifestyle-related diseases such as hyperlipidemia and obesity. PMID- 26352575 TI - Letter From the Editor: Inside my file cabinets. PMID- 26352574 TI - Age- and Gender-related Disparities in Primary Percutaneous Coronary Interventions for Acute ST-segment elevation Myocardial Infarction. AB - BACKGROUND: Previous analyses reported age- and gender-related differences in the provision of cardiac care. The objective of the study was to compare circadian disparities in the delivery of primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) according to the patient's age and gender. METHODS: We investigated patients included into the Acute Myocardial Infarction in Switzerland (AMIS) registry presenting to one of 11 centers in Switzerland providing primary PCI around the clock, and stratified patients according to gender and age. FINDINGS: A total of 4723 patients presented with AMI between 2005 and 2010; 1319 (28%) were women and 2172 (54%) were >=65 years of age. More than 90% of patients <65 years of age underwent primary PCI without differences between gender. Elderly patients and particularly women were at increased risk of being withheld primary PCI (males adj. HR 4.91, 95% CI 3.93-6.13; females adj. HR 9.31, 95% CI 7.37-11.75) as compared to males <65 years of age. An increased risk of a delay in door-to-balloon time >90 minutes was found in elderly males (adj HR 1.66 (95% CI 1.40-1.95), p<0.001) and females (adj HR 1.57 (95% CI 1.27-1.93), p<0.001), as well as in females <65 years (adj HR 1.47 (95% CI 1.13-1.91), p = 0.004) as compared to males <65 years of age, with significant differences in circadian patterns during on- and off-duty hours. CONCLUSIONS: In a cohort of patients with AMI in Switzerland, we observed discrimination of elderly patients and females in the circadian provision of primary PCI. PMID- 26352577 TI - Combination therapies for treating metastatic melanoma. PMID- 26352578 TI - Inhibition of cyclin-dependent kinases 4 and 6 in breast cancer. PMID- 26352579 TI - New developments in Richter syndrome. PMID- 26352580 TI - New drugs in ovarian cancer. PMID- 26352581 TI - The role of sorafenib in hepatocellular carcinoma. PMID- 26352582 TI - Novel therapeutic targets in multiple myeloma. AB - Multiple myeloma (MM) is a disorder of clonal plasma cells that accumulate in the bone marrow and secrete a monoclonal protein detectable in the blood and/or urine. In the last decade, the outcome of patients with MM has markedly improved owing to the introduction of agents such proteasome inhibitors (bortezomib) and immunomodulatory drugs (thalidomide, lenalidomide) as induction, consolidation, and maintenance strategies. Nonetheless, drug resistance leading to relapse commonly occurs, and novel therapies are urgently needed. In this review, we will describe the most promising new approaches to treat MM, including those based on targeting protein homeostasis, enhancing anti-MM immunity, targeting MM with monoclonal antibodies and immunotoxins, modulating bone metabolism, targeting histone modifications, targeting genomic instability and cell cycle alterations, and the use of genomic profiling to provide personalized therapies. These advances will continue to transform MM into a chronic illness, and have curative potential. PMID- 26352583 TI - Curative treatment for severe sickle cell disease: allogeneic transplantation. AB - Sickle cell disease is an inherited hematologic disorder that in its severe form can result in substantial morbidity and early mortality. Patients with this disorder can suffer from severe pain, lung disease, and strokes, resulting in chronic debilitating conditions, end organ dysfunction, and organ failure. The health care costs of caring for these chronically ill patients are substantial. Allogeneic transplantation is a modality that has the potential to cure these patients. To date, matched sibling donor transplantation is widely accepted as a standard of care for pediatric patients. Utilizing alternative donors for transplant is still under investigation, as is transplant for adult patients with sickle cell disease. This review focuses on the most recent data for hematopoietic cell transplantation for patients with sickle cell disease. PMID- 26352584 TI - Families with both Hodgkin lymphoma and multiple myeloma in their pedigrees. AB - Reports of familial clustering of hematologic malignancies have appeared for decades, but the cause of this uncommon observation is still unknown. Most modern investigations support a genetic rather than an environmental explanation. Clinically, most pedigrees of families with familial hematologic malignancies demonstrate age of onset anticipation (ie, diagnosis at an earlier age in successive generations). The cause of anticipation is clear in some familial neurologic disorders (eg, trinucleotide repeat expansion in Huntington disease) but unclear in familial hematologic malignancies. In preparation for molecular studies on familial clustering of hematologic malignancies, we collected pedigrees on 738 families. In these families, we observed anticipation in those with familial multiple myeloma, chronic lymphocytic leukemia, or non-Hodgkin lymphoma. Here we present preliminary data on 26 families with both multiple myeloma and Hodgkin lymphoma in their pedigrees, and demonstrate strong evidence for anticipation and predominantly male transmission of these neoplasms. We encourage all health care personnel to ask patients about their family's medical history, to take careful family histories from individuals with uncommon illnesses, and to refer families with clustering of such illnesses for investigation. PMID- 26352586 TI - Urban-Rural Differences in Cardiovascular Disease Risk Factors: A Cross-Sectional Study of Schoolchildren in Wuhan, China. AB - BACKGROUND: China's rapid population growth and urban migration has developed healthcare inequity across the urban-rural divide. Past studies comparing cardiovascular disease (CVD) risk factor prevalence amongst urban-rural Chinese children are sparse and conflicting. We examined the association between urban rural residence and risk of offspring CVD in Chinese children. METHODS: A cross sectional study was conducted in Wuhan, China, during May and June 2010. CVD risk factors include; waist circumference (WC), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), triglycerides (TG), high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, body mass index (BMI), cardiorespiratory fitness (CRF), metabolic syndrome (MetS), and metabolic risk score (MRS). Analysis of covariance and multivariable logistic regression were used to estimate associations between urban-rural residence and offspring CVD risks. FINDINGS: A total of 579 Chinese children (338 boys and 241 girls) aged 9.6 (0.7) years participated in this study. Rural boys had significantly lower CRF and higher FBG, TG, and MRS, while urban boys had significantly higher LDL and DBP. Rural girls had significantly higher BMI, FBG, and TG, as well as lower CRF. Rural children were at increased risks for decreased CRF, elevated MRS, and TG, (OR:2.04, 95%CI:1.29-3.25), (OR:2.33, 95%CI:1.50-3.62), and (OR:2.40, 95%CI:1.62-3.57), respectively. Rural girls and mothers were at increased risks for overweight(OR:7.19, 95%CI:1.64 31.6)/obesity (OR:1.683, 95%CI:1.01-2.82). However, rural boys and fathers were less likely to have overweight(OR:0.62, 95%CI:0.34-1.12)/obesity (OR:0.68, 95%CI:0.48-0.97). CONCLUSIONS: Rural residence was significantly associated with increased CVD risks amongst Chinese children. It is important to provide interventions aiming at China's urban-rural healthcare inequity and community based approaches that reduce familial CVD risk. PMID- 26352587 TI - Rapid Lymphatic Dissemination of Encapsulated Group A Streptococci via Lymphatic Vessel Endothelial Receptor-1 Interaction. AB - The host lymphatic network represents an important conduit for pathogen dissemination. Indeed, the lethal human pathogen group A streptococcus has a predilection to induce pathology in the lymphatic system and draining lymph nodes, however the underlying basis and subsequent consequences for disease outcome are currently unknown. Here we report that the hyaluronan capsule of group A streptococci is a crucial virulence determinant for lymphatic tropism in vivo, and further, we identify the lymphatic vessel endothelial receptor-1 as the critical host receptor for capsular hyaluronan in the lymphatic system. Interference with this interaction in vivo impeded bacterial dissemination to local draining lymph nodes and, in the case of a hyper-encapsulated M18 strain, redirected streptococcal entry into the blood circulation, suggesting a pivotal role in the manifestation of streptococcal infections. Our results reveal a novel function for bacterial capsular polysaccharide in directing lymphatic tropism, with potential implications for disease pathology. PMID- 26352588 TI - Single-Cell RNA-Seq of Bone Marrow-Derived Mesenchymal Stem Cells Reveals Unique Profiles of Lineage Priming. AB - The plasticity and immunomodulatory capacity of mesenchymal stem cells (MSCs) have spurred clinical use in recent years. However, clinical outcomes vary and many ascribe inconsistency to the tissue source of MSCs. Yet unconsidered is the extent of heterogeneity of individual MSCs from a given tissue source with respect to differentiation potential and immune regulatory function. Here we use single-cell RNA-seq to assess the transcriptional diversity of murine mesenchymal stem cells derived from bone marrow. We found genes associated with MSC multipotency were expressed at a high level and with consistency between individual cells. However, genes associated with osteogenic, chondrogenic, adipogenic, neurogenic and vascular smooth muscle differentiation were expressed at widely varying levels between individual cells. Further, certain genes associated with immunomodulation were also inconsistent between individual cells. Differences could not be ascribed to cycles of proliferation, culture bias or other cellular process, which might alter transcript expression in a regular or cyclic pattern. These results support and extend the concept of lineage priming of MSCs and emphasize caution for in vivo or clinical use of MSCs, even when immunomodulation is the goal, since multiple mesodermal (and even perhaps ectodermal) outcomes are a possibility. Purification might enable shifting of the probability of a certain outcome, but is unlikely to remove multilineage potential altogether. PMID- 26352589 TI - Reference ranges of lymphocyte subsets balanced for age and gender from a population of healthy adults in Chongqing District of China. AB - The enumeration of lymphocyte subsets plays an essential role in the monitoring of immunological disorders. Immunophenotyping values have been found to be influenced by race, age, gender, and environmental conditions. Therefore, it is important to establish reference ranges for healthy adults from the local population for clinical decision-making. The current study aimed to establish a normal reference range for peripheral blood lymphocyte subsets in healthy adults from the Chongqing District of China by using single-platform flow cytometry. Age and gender-specific reference ranges were established in 268 healthy adult males and females between 21 and 60 years of age. The CD8+ cell counts decreased with age, CD4+ cell percentages and counts increased with age, and total T cell percentages were higher in the female population. Our results are similar to those reported from other parts of China but different from some results reported from other countries; this further stresses the need to establish local reference ranges by region. Our results will help in the management of patients with human immunodeficiency virus and other immunological disorders in Chongqing District. (c) 2015 International Clinical Cytometry Society. PMID- 26352590 TI - A hybrid enrichment process combining conjugated polymer extraction and silica gel adsorption for high purity semiconducting single-walled carbon nanotubes (SWCNT). AB - A novel purification process for the enrichment of sc-SWCNTs that combines selective conjugated polymer extraction (CPE) with selective adsorption using silica gel, termed hybrid-CPE (h-CPE), has been developed, providing a high purity sc-SWCNT material with a significant improvement in process efficiency and yield. Using the h-CPE protocol, a greater than 5 fold improvement in yield can be obtained compared to traditional CPE while obtaining sc-SWCNT with a purity >99.9% as assessed by absorption spectroscopy and Raman mapping. Thin film transistor devices using the h-CPE derived sc-SWCNTs as the semiconductor possess mobility values ranging from 10-30 cm(2) V(-1) s(-1) and current ON/OFF ratio of 10(4)-10(5) for channel lengths between 2.5 and 20 MUm. PMID- 26352591 TI - Point Mutations in Centromeric Histone Induce Post-zygotic Incompatibility and Uniparental Inheritance. AB - The centromeric histone 3 variant (CENH3, aka CENP-A) is essential for the segregation of sister chromatids during mitosis and meiosis. To better define CENH3 functional constraints, we complemented a null allele in Arabidopsis with a variety of mutant alleles, each inducing a single amino acid change in conserved residues of the histone fold domain. Many of these transgenic missense lines displayed wild-type growth and fertility on self-pollination, but exhibited frequent post-zygotic death and uniparental inheritance when crossed with wild type plants. The failure of centromeres marked by these missense mutation in the histone fold domain of CENH3 reproduces the genome elimination syndromes described with chimeric CENH3 and CENH3 from diverged species. Additionally, evidence that a single point mutation is sufficient to generate a haploid inducer provide a simple one-step method for the identification of non-transgenic haploid inducers in existing mutagenized collections of crop species. As proof of the extreme simplicity of this approach to create haploid-inducing lines, we performed an in silico search for previously identified point mutations in CENH3 and identified an Arabidopsis line carrying the A86V substitution within the histone fold domain. This A87V non-transgenic line, while fully fertile on self pollination, produced postzygotic death and uniparental haploids when crossed to wild type. PMID- 26352592 TI - Expression and purification of functional HMGB1 A box by fusion with SUMO. AB - High-mobility-group-box chromosomal protein 1 (HMGB1) is a ubiquitous and abundant nuclear protein in eukaryotic cells. Nuclear HMGB1 serves an important role in maintaining nuclear stability under stress. However, extracellular HMGB1 exerts actions, which are distinctly different compared with these intracellular functions. HMGB1, when released extracellularly, is a potent innate signal, which initiates host defense mechanisms or tissue regeneration. HMGB1 has two DNA binding domains: HMG A box and B box. The HMGB1 A box exhibits an antagonistic, anti-inflammatory effect, and is a potential therapeutic target, however, the large-scale expression and purification of the HMGB1 A box with high efficiency remains to be reported. In the present study, a SUMO-fusion expression system was used to express and purify high levels of functional HMGB1 A box to meet the requirements of therapeutic protein production. PMID- 26352593 TI - Corticotropin-Releasing Hormone Receptor Type 1 (CRHR1) Clustering with MAGUKs Is Mediated via Its C-Terminal PDZ Binding Motif. AB - The corticotropin-releasing hormone receptor type 1 (CRHR1) plays an important role in orchestrating neuroendocrine, behavioral, and autonomic responses to stress. To identify molecules capable of directly modulating CRHR1 signaling, we performed a yeast-two-hybrid screen using the C-terminal intracellular tail of the receptor as bait. We identified several members of the membrane-associated guanylate kinase (MAGUK) family: postsynaptic density protein 95 (PSD95), synapse associated protein 97 (SAP97), SAP102 and membrane associated guanylate kinase, WW and PDZ domain containing 2 (MAGI2). CRHR1 is co-expressed with the identified MAGUKs and with the additionally investigated PSD93 in neurons of the adult mouse brain and in primary hippocampal neurons, supporting the probability of a physiological interaction in vivo. The C-terminal PDZ (PSD-95, discs large, zona occludens 1) binding motif of CRHR1 is essential for its physical interaction with MAGUKs, as revealed by the CRHR1-STAVA mutant, which harbors a functionally impaired PDZ binding motif. The imitation of a phosphorylation at Thr413 within the PDZ binding motif also disrupted the interaction with MAGUKs. In contrast, distinct PDZ domains within the identified MAGUKs are involved in the interactions. Expression of CRHR1 in primary neurons demonstrated its localization throughout the neuronal plasma membrane, including the excitatory post synapse, where the receptor co-localized with PSD95 and SAP97. The co expression of CRHR1 and respective interacting MAGUKs in HEK293 cells resulted in a clustered subcellular co-localization which required an intact PDZ binding motif. In conclusion, our study characterized the PDZ binding motif-mediated interaction of CRHR1 with multiple MAGUKs, which directly affects receptor function. PMID- 26352594 TI - Response Properties of a Newly Identified Tristratified Narrow Field Amacrine Cell in the Mouse Retina. AB - Amacrine cells were targeted for whole cell recording using two-photon fluorescence microscopy in a transgenic mouse line in which the promoter for dopamine receptor 2 drove expression of green fluorescent protein in a narrow field tristratified amacrine cell (TNAC) that had not been studied previously. Light evoked a multiphasic response that was the sum of hyperpolarizing and depolarization synaptic inputs consistent with distinct dendritic ramifications in the off and on sublamina of the inner plexiform layer. The amplitude and waveform of the response, which consisted of an initial brief hyperpolarization at light onset followed by recovery to a plateau potential close to dark resting potential and a hyperpolarizing response at the light offset varied little over an intensity range from 0.4 to ~10^6 Rh*/rod/s. This suggests that the cell functions as a differentiator that generates an output signal (a transient reduction in inhibitory input to downstream retina neurons) that is proportional to the derivative of light input independent of its intensity. The underlying circuitry appears to consist of rod and cone driven on and off bipolar cells that provide direct excitatory input to the cell as well as to GABAergic amacrine cells that are synaptically coupled to TNAC. Canonical reagents that blocked excitatory (glutamatergic) and inhibitory (GABA and glycine) synaptic transmission had effects on responses to scotopic stimuli consistent with the rod driven component of the proposed circuit. However, responses evoked by photopic stimuli were paradoxical and could not be interpreted on the basis of conventional thinking about the neuropharmacology of synaptic interactions in the retina. PMID- 26352595 TI - Complete (1)H and (13)C NMR assignments of a series of pergalloylated tannins. PMID- 26352596 TI - The Topology of a Discussion: The #Occupy Case. AB - INTRODUCTION: We analyse a large sample of the Twitter activity that developed around the social movement 'Occupy Wall Street', to study the complex interactions between the human communication activity and the semantic content of a debate. METHODS: We use a network approach based on the analysis of the bipartite graph @Users-#Hashtags and of its projections: the 'semantic network', whose nodes are hashtags, and the 'users interest network', whose nodes are users. In the first instance, we find out that discussion topics (#hashtags) present a high structural heterogeneity, with a relevant role played by the semantic hubs that are responsible to guarantee the continuity of the debate. In the users' case, the self-organisation process of users' activity, leads to the emergence of two classes of communicators: the 'professionals' and the 'amateurs'. RESULTS: Both the networks present a strong community structure, based on the differentiation of the semantic topics, and a high level of structural robustness when certain sets of topics are censored and/or accounts are removed. CONCLUSIONS: By analysing the characteristics of the dynamical networks we can distinguish three phases of the discussion about the movement. Each phase corresponds to a specific moment of the movement: from declaration of intent, organisation and development and the final phase of political reactions. Each phase is characterised by the presence of prototypical #hashtags in the discussion. PMID- 26352597 TI - "Omics" Insights into PAH Degradation toward Improved Green Remediation Biotechnologies. AB - This review summarizes recent knowledge of polycyclic aromatic hydrocarbons (PAHs) biotransformation by microorganisms and plants. Whereas most research has focused on PAH degradation either by plants or microorganisms separately, this review specifically addresses the interactions of plants with their rhizosphere microbial communities. Indeed, plant roots release exudates that contain various nutritional and signaling molecules that influence bacterial and fungal populations. The complex interactions of these populations play a pivotal role in the biodegradation of high-molecular-weight PAHs and other complex molecules. Emerging integrative approaches, such as (meta-) genomics, (meta-) transcriptomics, (meta-) metabolomics, and (meta-) proteomics studies are discussed, emphasizing how "omics" approaches bring new insight into decipher molecular mechanisms of PAH degradation both at the single species and community levels. Such knowledge address new pictures on how organic molecules are cometabolically degraded in a complex ecosystem and should help in setting up novel decontamination strategies based on the rhizosphere interactions between plants and their microbial associates. PMID- 26352598 TI - Dectin-1 Polymorphism: A Genetic Disease Specifier in Autism Spectrum Disorders? AB - INTRODUCTION: In autism spectrum disorders (ASD), complex gene-environment interactions contribute to disease onset and progress. Given that gastro intestinal dysfunctions are common in ASD, we postulated involvement of microbial dysbiosis in ASD and investigated, under a case-control design, the influence of DNA polymorphisms in the CLEC7A gene that encodes a pivotal fungal sensor, Dectin 1. MATERIAL AND METHODS: DNAs from 478 ASD patients and 351 healthy controls (HC) were analyzed for the CLEC7A rs16910631G/A and rs2078178 A/G single nucleotide polymorphisms (SNPs). Differences in the distribution of allele, genotype and haplotype by Chi-square testing and nonparametric analysis by Kruskal-Wallis/Mann Whitney tests, where appropriate, were performed. The free statistical package R.2.13 software was used for the statistical analysis. RESULTS: We found that the CLEC7A rs2078178 G allele and GG genotype were more prevalent in HC as compared to ASD but failed to reach statistical significance for the latter (pc = 0.01, 0.06 respectively). However, after phenotype-based stratification, the CLEC7A rs2078178 G allele and GG genotype were found to be significantly more frequent in the Asperger group as compared to other ASD subsets (pc = 0.02, 0.01), a finding reinforced by haplotype analysis (rs2078178/rs16910631 G-G/G-G) (pc = 0.002). Further, intellectual quotient (IQ)-based stratification of ASD patients revealed that IQ values increase linearly along the CLEC7A rs2078178 AA, AG and GG genotypes (p = 0.05) and in a recessive manner (GG vs. AA+AG p = 0.02), further confirmed by haplotype distribution (CLEC7A rs2078178-16910631; A-G/A-G, A-G/G-G and G-G/G-G, p = 0.02, G-G/G-G vs. others, p = 0.01). CONCLUSION: Our data suggest that the genetic diversity of CLEC7A gene influences the ASD phenotype by behaving as a disease specifier and imply that the genetic control of innate immune response could determine the ASD phenotype. PMID- 26352599 TI - HDAC1 and HDAC2 independently predict mortality in hepatocellular carcinoma by a competing risk regression model in a Southeast Asian population. AB - Histone deacetylases (HDACs) are enzymes involved in transcriptional repression. We aimed to examine the significance of HDAC1 and HDAC2 gene expression in the prediction of recurrence and survival in 156 patients with hepatocellular carcinoma (HCC) among a South East Asian population who underwent curative surgical resection in Singapore. We found that HDAC1 and HDAC2 were upregulated in the majority of HCC tissues. The presence of HDAC1 in tumor tissues was correlated with poor tumor differentiation. Notably, HDAC1 expression in adjacent non-tumor hepatic tissues was correlated with the presence of satellite nodules and multiple lesions, suggesting that HDAC1 upregulation within the field of HCC may contribute to tumor spread. Using competing risk regression analysis, we found that increased cancer-specific mortality was significantly associated with HDAC2 expression. Mortality was also increased with high HDAC1 expression. In the liver cancer cell lines, HEP3B, HEPG2, PLC5, and a colorectal cancer cell line, HCT116, the combined knockdown of HDAC1 and HDAC2 increased cell death and reduced cell proliferation as well as colony formation. In contrast, knockdown of either HDAC1 or HDAC2 alone had minimal effects on cell death and proliferation. Taken together, our study suggests that both HDAC1 and HDAC2 exert pro-survival effects in HCC cells, and the combination of isoform-specific HDAC inhibitors against both HDACs may be effective in targeting HCC to reduce mortality. PMID- 26352600 TI - 30-Day Survival Probabilities as a Quality Indicator for Norwegian Hospitals: Data Management and Analysis. AB - BACKGROUND: The Norwegian Knowledge Centre for the Health Services (NOKC) reports 30-day survival as a quality indicator for Norwegian hospitals. The indicators have been published annually since 2011 on the website of the Norwegian Directorate of Health (www.helsenorge.no), as part of the Norwegian Quality Indicator System authorized by the Ministry of Health. Openness regarding calculation of quality indicators is important, as it provides the opportunity to critically review and discuss the method. The purpose of this article is to describe the data collection, data pre-processing, and data analyses, as carried out by NOKC, for the calculation of 30-day risk-adjusted survival probability as a quality indicator. METHODS AND FINDINGS: Three diagnosis-specific 30-day survival indicators (first time acute myocardial infarction (AMI), stroke and hip fracture) are estimated based on all-cause deaths, occurring in-hospital or out of-hospital, within 30 days counting from the first day of hospitalization. Furthermore, a hospital-wide (i.e. overall) 30-day survival indicator is calculated. Patient administrative data from all Norwegian hospitals and information from the Norwegian Population Register are retrieved annually, and linked to datasets for previous years. The outcome (alive/death within 30 days) is attributed to every hospital by the fraction of time spent in each hospital. A logistic regression followed by a hierarchical Bayesian analysis is used for the estimation of risk-adjusted survival probabilities. A multiple testing procedure with a false discovery rate of 5% is used to identify hospitals, hospital trusts and regional health authorities with significantly higher/lower survival than the reference. In addition, estimated risk-adjusted survival probabilities are published per hospital, hospital trust and regional health authority. The variation in risk-adjusted survival probabilities across hospitals for AMI shows a decreasing trend over time: estimated survival probabilities for AMI in 2011 varied from 80.6% (in the hospital with lowest estimated survival) to 91.7% (in the hospital with highest estimated survival), whereas it ranged from 83.8% to 91.2% in 2013. CONCLUSIONS: Since 2011, several hospitals and hospital trusts have initiated quality improvement projects, and some of the hospitals have improved the survival over these years. Public reporting of survival/mortality indicators are increasingly being used as quality measures of health care systems. Openness regarding the methods used to calculate the indicators are important, as it provides the opportunity of critically reviewing and discussing the methods in the literature. In this way, the methods employed for establishing the indicators may be improved. PMID- 26352601 TI - Integrated Analyses of Gene Expression Profiles Digs out Common Markers for Rheumatic Diseases. AB - OBJECTIVE: Rheumatic diseases have some common symptoms. Extensive gene expression studies, accumulated thus far, have successfully identified signature molecules for each rheumatic disease, individually. However, whether there exist shared factors across rheumatic diseases has yet to be tested. METHODS: We collected and utilized 6 public microarray datasets covering 4 types of representative rheumatic diseases including rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, and osteoarthritis. Then we detected overlaps of differentially expressed genes across datasets and performed a meta analysis aiming at identifying common differentially expressed genes that discriminate between pathological cases and normal controls. To further gain insights into the functions of the identified common differentially expressed genes, we conducted gene ontology enrichment analysis and protein-protein interaction analysis. RESULTS: We identified a total of eight differentially expressed genes (TNFSF10, CX3CR1, LY96, TLR5, TXN, TIA1, PRKCH, PRF1), each associated with at least 3 of the 4 studied rheumatic diseases. Meta-analysis warranted the significance of the eight genes and highlighted the general significance of four genes (CX3CR1, LY96, TLR5, and PRF1). Protein-protein interaction and gene ontology enrichment analyses indicated that the eight genes interact with each other to exert functions related to immune response and immune regulation. CONCLUSION: The findings support that there exist common factors underlying rheumatic diseases. For rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis and osteoarthritis diseases, those common factors include TNFSF10, CX3CR1, LY96, TLR5, TXN, TIA1, PRKCH, and PRF1. In-depth studies on these common factors may provide keys to understanding the pathogenesis and developing intervention strategies for rheumatic diseases. PMID- 26352602 TI - Stroke preparedness in children: translating knowledge into behavioral intent: a systematic review and meta-analysis. AB - BACKGROUND: If translated into behavioral intent, improving stroke knowledge may potentially impact on better outcomes. Children are an attractive target population since they can drive familial behavioral changes. However, the impact of interventions on stroke knowledge among children is unclear. We performed a systematic review and meta-analysis to investigate whether educational interventions targeting children improve stroke knowledge and lead to behavioral changes. METHODS: We searched Ovid, PubMed, and Embase between January 2000 and December 2014. We included studies written in English reporting the number of children aged 6-15 years undergoing educational interventions on stroke and providing the results for baseline and early and late postintervention tests. We compared the proportion of correct answers between baseline, early, and late responses for two endpoints: knowledge and behavioral intent. RESULTS: Of the initial 58 articles found, we included nine that met the inclusion criteria. Compared with baseline tests (51.7%, 95% confidence interval 40.9-62.4), there was improvement in stroke knowledge in early (74.0%, 95% confidence interval 64.4 82.5, P = 0.002) and late (67.3%, 95% confidence interval 55.4-78.2, P = 0.027) responses. There was improvement in the early (92.1%, 95% confidence interval 86.0-96.6, P < 0.001) and late (83.9%, 95% confidence interval 73.5-92.1, P = 0.001) responses for behavioral intent compared with the baseline assessment (63.8%, 95% confidence interval 53.5-73.4). CONCLUSION: Children are a potentially attractive target population for improvement in stroke knowledge and behavioral intent, both in the short and long term. Our findings may support the implementation of large-scale stroke educational initiatives targeting children. PMID- 26352603 TI - The Role of Temporal Information in Perisaccadic Mislocalization. AB - In dynamic environments, it is crucial to accurately consider the timing of information. For instance, during saccades the eyes rotate so fast that even small temporal errors in relating retinal stimulation by flashed stimuli to extra retinal information about the eyes' orientations will give rise to substantial errors in where the stimuli are judged to be. If spatial localization involves judging the eyes' orientations at the estimated time of the flash, we should be able to manipulate the pattern of mislocalization by altering the estimated time of the flash. We reasoned that if we presented a relevant flash within a short rapid sequence of irrelevant flashes, participants' estimates of when the relevant flash was presented might be shifted towards the centre of the sequence. In a first experiment, we presented five bars at different positions around the time of a saccade. Four of the bars were black. Either the second or the fourth bar in the sequence was red. The task was to localize the red bar. We found that when the red bar was presented second in the sequence, it was judged to be further in the direction of the saccade than when it was presented fourth in the sequence. Could this be because the red bar was processed faster when more black bars preceded it? In a second experiment, a red bar was either presented alone or followed by two black bars. When two black bars followed it, it was judged to be further in the direction of the saccade. We conclude that the spatial localization of flashed stimuli involves judging the eye orientation at the estimated time of the flash. PMID- 26352604 TI - Quantitative Analysis of the Interdisciplinarity of Applied Mathematics. AB - The increasing use of mathematical techniques in scientific research leads to the interdisciplinarity of applied mathematics. This viewpoint is validated quantitatively here by statistical and network analysis on the corpus PNAS 1999 2013. A network describing the interdisciplinary relationships between disciplines in a panoramic view is built based on the corpus. Specific network indicators show the hub role of applied mathematics in interdisciplinary research. The statistical analysis on the corpus content finds that algorithms, a primary topic of applied mathematics, positively correlates, increasingly co occurs, and has an equilibrium relationship in the long-run with certain typical research paradigms and methodologies. The finding can be understood as an intrinsic cause of the interdisciplinarity of applied mathematics. PMID- 26352605 TI - ApoG2 inhibits the antiapoptotic protein, Mcl-1, and induces mitochondria dependent apoptosis in human colorectal cancer cells. AB - Colorectal cancer (CRC) is a worldwide malignancy of high incidence and mortality. At present, there is a lack of effective drugs against CRC. The B-cell leukemia/lymphoma 2 (Bcl-2) protein family members are considered to be closely associated with tumorigenesis and the chemoresistance of CRC. As a novel gossypol derivative targeting antiapoptotic proteins of the Bcl-2 family, apogossypolone (ApoG2) exhibits antitumor properties in various cancer types, although its effects against CRC remain to be fully elucidated. In the present study, the cytotoxicity of ApoG2 in vitro on CRC cells was investigated, with the aim of elucidating the underlying mechanism. Using an MTT assay, ApoG2 was revealed to inhibit the growth of the HT29, SW480 and HCT116 CRC cell lines in a dose- and a time-dependent manner. Hoechst staining revealed that ApoG2 induced CRC cell apoptosis, marked by morphological changes, including cell shrinkage and nuclear fragmentation. Flow cytometric analysis also detected a higher apoptotic ratio following treatment with ApoG2. The ratio was dependent upon the concentration of ApoG2, which the cells were exposed to, and the duration of the exposure. Western blot analysis and immunoprecipitation experiments revealed that ApoG2 treatment led to the downregulation of the protein expression of Mcl-1, and the interruption of the binding of Mcl-1 to the protein Bax. Furthermore, treatment with ApoG2 led to the release of cytochrome c into the cytoplasm and the activation of caspases 3 and 7. The present study revealed that ApoG2 inhibited the proliferation of the CRC cell lines through mitochondrial signaling pathway dependent apoptosis, which may be associated with the disruption of the function of the Mcl-1 protein by ApoG2. PMID- 26352606 TI - Healthcare Costs Associated with an Adequate Intake of Sugars, Salt and Saturated Fat in Germany: A Health Econometrical Analysis. AB - Non-communicable diseases (NCDs) represent not only the major driver for quality restricted and lost life years; NCDs and their related medical treatment costs also pose a substantial economic burden on healthcare and intra-generational tax distribution systems. The main objective of this study was therefore to quantify the economic burden of unbalanced nutrition in Germany--in particular the effects of an excessive consumption of fat, salt and sugar--and to examine different reduction scenarios on this basis. In this study, the avoidable direct cost savings in the German healthcare system attributable to an adequate intake of saturated fatty acids (SFA), salt and sugar (mono- & disaccharides, MDS) were calculated. To this end, disease-specific healthcare cost data from the official Federal Health Monitoring for the years 2002-2008 and disease-related risk factors, obtained by thoroughly searching the literature, were used. A total of 22 clinical endpoints with 48 risk-outcome pairs were considered. Direct healthcare costs attributable to an unbalanced intake of fat, salt and sugar are calculated to be 16.8 billion EUR (CI95%: 6.3-24.1 billion EUR) in the year 2008, which represents 7% (CI95% 2%-10%) of the total treatment costs in Germany (254 billion EUR). This is equal to 205 EUR per person annually. The excessive consumption of sugar poses the highest burden, at 8.6 billion EUR (CI95%: 3.0 12.1); salt ranks 2nd at 5.3 billion EUR (CI95%: 3.2-7.3) and saturated fat ranks 3rd at 2.9 billion EUR (CI95%: 32 million-4.7 billion). Predicted direct healthcare cost savings by means of a balanced intake of sugars, salt and saturated fat are substantial. However, as this study solely considered direct medical treatment costs regarding an adequate consumption of fat, salt and sugars, the actual societal and economic gains, resulting both from direct and indirect cost savings, may easily exceed 16.8 billion EUR. PMID- 26352612 TI - Treatment Progress of Paroxysmal Sympathetic Hyperactivity after Acquired Brain Injury. AB - Paroxysmal sympathetic hyperactivity (PSH) is a common complication of various acquired brain injuries such as traumatic brain injury, subarachnoid hemorrhage, anoxic brain injury, intracerebral hemorrhage, and others. It is manifested by tachycardia, hypertension, tachypnea, diaphoresis, and dystonic posturing. The development of PSH can prolong hospitalization and lead to secondary brain injury and even death. Despite the awareness of the serious clinical impact, there is no consensus on diagnostic criteria. Thus, misdiagnosis and delayed recognition is very common. Most of the current treatment programs come from case reports and small case series; there are very few large-scale randomized controlled trials. Generally accepted medications are opioids, beta-blockers and gabapentin (usually used in combination). However, the efficacy of these drugs has not been systematically assessed. The purpose of this review is to determine the treatment strategies and drugs commonly used for PSH at the overall level. PMID- 26352611 TI - The Spatial Distribution of Hepatitis C Virus Infections and Associated Determinants--An Application of a Geographically Weighted Poisson Regression for Evidence-Based Screening Interventions in Hotspots. AB - BACKGROUND: Hepatitis C Virus (HCV) infections are a major cause for liver diseases. A large proportion of these infections remain hidden to care due to its mostly asymptomatic nature. Population-based screening and screening targeted on behavioural risk groups had not proven to be effective in revealing these hidden infections. Therefore, more practically applicable approaches to target screenings are necessary. Geographic Information Systems (GIS) and spatial epidemiological methods may provide a more feasible basis for screening interventions through the identification of hotspots as well as demographic and socio-economic determinants. METHODS: Analysed data included all HCV tests (n = 23,800) performed in the southern area of the Netherlands between 2002-2008. HCV positivity was defined as a positive immunoblot or polymerase chain reaction test. Population data were matched to the geocoded HCV test data. The spatial scan statistic was applied to detect areas with elevated HCV risk. We applied global regression models to determine associations between population-based determinants and HCV risk. Geographically weighted Poisson regression models were then constructed to determine local differences of the association between HCV risk and population-based determinants. RESULTS: HCV prevalence varied geographically and clustered in urban areas. The main population at risk were middle-aged males, non-western immigrants and divorced persons. Socio-economic determinants consisted of one-person households, persons with low income and mean property value. However, the association between HCV risk and demographic as well as socio-economic determinants displayed strong regional and intra-urban differences. DISCUSSION: The detection of local hotspots in our study may serve as a basis for prioritization of areas for future targeted interventions. Demographic and socio-economic determinants associated with HCV risk show regional differences underlining that a one-size-fits-all approach even within small geographic areas may not be appropriate. Future screening interventions need to consider the spatially varying association between HCV risk and associated demographic and socio-economic determinants. PMID- 26352613 TI - Morphology evolution and gas adsorption of porous metal-organic framework microcrystals. AB - A facile and controllable synthesis of porous framework [Cu3(L)2(DABCO)] (1) (H3L = 1,1':3,1''-terphenyl]-4,4'',5'-tricarboxylic acid; DABCO = 1,4 diazabicyclo[2.2.2]octane) microcrystals was realized with morphology evolution from a tetragonal plate to an elongated tetragonal bipyramid, and the particle size changes by tuning the volume ratio of mixed solvents of DMF and H2O. Interestingly, the exposed high-energy {103} crystal facet can be easily tuned by controlling the supersaturation through the increase of the solution concentration, resulting in the formation of spindle microcrystals. It was found that both H2O and HCl play important roles in the morphology evolution process. The gas adsorption properties were found to be dependent on the morphology of microcrystals, and the elongated tetragonal bipyramidal microcrystals show the largest BET surface area. PMID- 26352614 TI - Audience effects, but not environmental influences, explain variation in gorilla close distance vocalizations-A test of the acoustic adaptation hypothesis. AB - Close distance vocalizations are an integral part of primate vocal communication. They exhibit large acoustic variation which has been suggested to constitute flexible responses to the highly variable social setting of group living animals. However, a recent study suggested that acoustic variation in close distance calls of baboons may also arise from acoustic adaptations to environmental factors in order to counteract sound degradation. We tested whether the variation in calling rate and acoustic structure of gorilla close distance vocalizations may serve to counteract distorting effects of vegetation during sound propagation. Using focal animal sampling we recorded the vocal behavior of 15 adult individuals living in two groups: one group of western lowland gorillas Gorilla gorilla gorilla and one group of mountain gorillas Gorilla beringei beringei. We considered the distance between the caller and its nearest neighbor as the minimum transmission distance of calls; while vegetation density was quantified through measures of visibility. Our analysis revealed vocal plasticity in gorilla close calls in relation to changes in visibility and nearest neighbor distance. However, the observed changes in fundamental frequency and calling rate are unlikely to counteract degrading effects of vegetation, but rather seem to reflect reactions to variation in spatial and visual separation from other group members, similar to the audience effects demonstrated in a range of other species. We propose that vocal plasticity to counteract distorting environmental effects may not be prevalent across taxa and perhaps confined to species living in heterogeneous habitats with highly variable transmission conditions. PMID- 26352615 TI - Ubiquitin-conjugated degradation of golden 2-like transcription factor is mediated by CUL4-DDB1-based E3 ligase complex in tomato. AB - CULLIN4-RING ubiquitin ligases (CRL4s) as well as their targets are fundamental regulators functioning in many key developmental and stress responses in eukaryotes. In tomato (Solanum lycopersicum), molecular cloning has revealed that the underlying genes of natural spontaneous mutations high pigment 1 (hp1), high pigment 2 (hp2) and uniform ripening (u) encode UV-DAMAGED DNA BINDING PROTEIN 1 (DDB1), DE-ETIOLATED 1 (DET1) and GOLDEN 2-LIKE (GLK2), respectively. However, the molecular basis of the opposite actions of tomato GLK2 vs CUL4-DDB1-DET1 complex on regulating plastid level and fruit quality remains unknown. Here, we provide molecular evidence showing that the tomato GLK2 protein is a substrate of the CUL4-DDB1-DET1 ubiquitin ligase complex for the proteasome degradation. SlGLK2 is degraded by the ubiquitin-proteasome system, which is mainly determined by two lysine residues (K11 and K253). SlGLK2 associates with the CUL4-DDB1-DET1 E3 complex in plant cells. Genetically impairing CUL4, DDB1 or DET1 results in a retardation of SlGLK2 degradation by the 26S proteasome. These findings are relevant to the potential of nutrient accumulation in tomato fruit by mediating the plastid level and contribute to a deeper understanding of an important regulatory loop, linking protein turnover to gene regulation. PMID- 26352616 TI - Single-energy intensity modulated proton therapy. AB - In this note, an intensity modulated proton therapy (IMPT) technique, based on the use of high single-energy (SE-IMPT) pencil beams, is described.The method uses only the highest system energy (226 MeV) and only lateral penumbra to produce dose gradient, as in photon therapy. In the study, after a preliminary analysis of the width of proton pencil beam penumbras at different depths, SE IMPT was compared with conventional IMPT in a phantom containing titanium inserts and in a patient, affected by a spinal chordoma with fixation rods.It was shown that SE-IMPT has the potential to produce a sharp dose gradient and that it is not affected by the uncertainties produced by metal implants crossed by the proton beams. Moreover, in the chordoma patient, target coverage and organ at risk sparing of the SE-IMPT plan resulted comparable to that of the less reliable conventional IMPT technique. Robustness analysis confirmed that SE-IMPT was not affected by range errors, which can drastically affect the IMPT plan.When accepting a low-dose spread as in modern photon techniques, SE-IMPT could be an option for the treatment of lesions (e.g. cervical bone tumours) where steep dose gradient could improve curability, and where range uncertainty, due for example to the presence of metal implants, hampers conventional IMPT. PMID- 26352621 TI - Preferential Stereocomplex Crystallization in Enantiomeric Blends of Cellulose Acetate-g-Poly(lactic acid)s with Comblike Topology. AB - Although stereocomplex (sc) crystallization is highly effective for improving the thermal resistance of poly(lactic acid) (PLA), it is much less predominant than homocrystallization in high-molecular-weight (HMW) poly(l-lactic acid)/ poly(d lactic acid) (PLLA/PDLA) racemic blends. In this contribution, the sc crystallization of HMW PLLA/PDLA racemic blends was facilitated by using comblike PLAs with cellulose acetate as the backbone. Competing crystallization kinetics, polymorphic crystalline structure, and structural transition of comblike PLLA/PDLA blends with a wide range of MWs were investigated and compared with the corresponding linear/comblike and linear blends. The HMW comblike blend is preferentially crystallized in sc polymorphs and exhibits a faster crystallization rate than does the corresponding linear blend. The sc crystallites are predominantly formed in nonisothermal cold crystallization and isothermal crystallization at temperatures above 120 degrees C for the comblike blends. Except for the facilitated sc formation in primary crystallization, synchrotron radiation WAXD analysis indicates that the presence of a comblike component also facilitates the transition or recrystallization from homocrystallite (hc) to sc crystallite upon heating. Preferential sc formation of comblike blends is probably attributable to the favorable interdigitation between enantiomeric branches and the increased mobility of polymer segments. After crystallization under the same temperature, the comblike blends, which mainly contain sc crystallites, show smaller long periods and thinner crystalline lamellae than do the corresponding PLLA with homocrystalline structures. PMID- 26352622 TI - A Natural Interruption Displays Higher Global Stability and Local Conformational Flexibility than a Similar Gly Mutation Sequence in Collagen Mimic Peptides. AB - Natural interruptions in the repeating (Gly-X-Y)n amino acid sequence pattern are found normally in triple helix domains of all nonfibrillar collagens, while any Gly substitution in fibrillar collagens leads to pathological conditions. As revealed by our sequence analysis, two peptides, one modeling a natural G5G interruption (POALO) and the other one mimicking a pathological Gly-to-Ala substitution (LOAPO), are designed. Circular dichroism (CD), NMR, and computational simulation studies have discovered significant differences in stability, conformation, and folding between the two peptides. Compared with the Gly substitution sequence, the natural interruption maintains higher stability, higher triple helix content, and a higher folding rate while introducing more alterations in local triple helical conformation in terms of dihedral angles and hydrogen bonding. The conserved hydrophobic residues at the specific sites of interruptions may provide functional constraints for higher-order assembly as well as biomolecular interactions. These results suggest a molecular basis of different biological roles of natural interruptions and Gly substitutions and may guide the design of collagen mimic peptides containing functional natural interruptions. PMID- 26352623 TI - Contribution of Adsorbed Protein Films to Nanoscopic Vibrations Exhibited by Bacteria Adhering through Ligand-Receptor Bonds. AB - Bacteria adhering to surfaces exhibit nanoscopic vibrations that depend on the viscoelasticity of the bond. The quantification of the nanoscopic vibrations of bacteria adhering to surfaces provides new opportunities to better understand the properties of the bond through which bacteria adhere and the mechanisms by which they resist detachment. Often, however, bacteria do not adhere to bare surfaces but to adsorbed protein films, on which adhesion involves highly specific ligand receptor binding next to nonspecific DLVO interaction forces. Here we determine the contribution of adsorbed salivary protein and fibronectin films to vibrations exhibited by adhering streptococci and staphylococci, respectively. The streptococcal strain used has the ability to adhere to adsorbed salivary proteins films through antigen I/II ligand-receptor binding, while the staphylococcal strain used adheres to adsorbed fibronectin films through a proteinaceous ligand receptor bond. In the absence of ligand-receptor binding, electrostatic interactions had a large impact on vibration amplitudes of adhering bacteria on glass. On an adsorbed salivary protein film, vibration amplitudes of adhering streptococci depended on the film softness as determined by QCM-D and were reduced after film fixation using glutaraldehyde. On a relatively stiff fibronectin film, cross-linking the film in glutaraldehyde hardly reduced its softness, and accordingly fibronectin film softness did not contribute to vibration amplitudes of adhering staphylococci. However, fixation of the staphylococcus-fibronectin bond further decreased vibration amplitudes, while fixation of the streptococcus bond hardly impacted vibration amplitudes. Summarizing, this study shows that both the softness of adsorbed protein films and the properties of the bond between an adhering bacterium and an adsorbed protein film play an important role in bacterial vibration amplitudes. These nanoscopic vibrations reflect the viscoelasticity of the bacterial bond with a substratum and play important roles in bacterial adhesion, detachment and susceptibility to antimicrobials. PMID- 26352624 TI - A Framework for Analysis of Computational Imaging Systems: Role of Signal Prior, Sensor Noise and Multiplexing. AB - Over the last decade, a number of computational imaging (CI) systems have been proposed for tasks such as motion deblurring, defocus deblurring and multispectral imaging. These techniques increase the amount of light reaching the sensor via multiplexing and then undo the deleterious effects of multiplexing by appropriate reconstruction algorithms. Given the widespread appeal and the considerable enthusiasm generated by these techniques, a detailed performance analysis of the benefits conferred by this approach is important. Unfortunately, a detailed analysis of CI has proven to be a challenging problem because performance depends equally on three components: (1) the optical multiplexing, (2) the noise characteristics of the sensor, and (3) the reconstruction algorithm which typically uses signal priors. A few recent papers [12], [30], [49] have performed analysis taking multiplexing and noise characteristics into account. However, analysis of CI systems under state-of-the-art reconstruction algorithms, most of which exploit signal prior models, has proven to be unwieldy. In this paper, we present a comprehensive analysis framework incorporating all three components. In order to perform this analysis, we model the signal priors using a Gaussian Mixture Model (GMM). A GMM prior confers two unique characteristics. First, GMM satisfies the universal approximation property which says that any prior density function can be approximated to any fidelity using a GMM with appropriate number of mixtures. Second, a GMM prior lends itself to analytical tractability allowing us to derive simple expressions for the 'minimum mean square error' (MMSE) which we use as a metric to characterize the performance of CI systems. We use our framework to analyze several previously proposed CI techniques (focal sweep, flutter shutter, parabolic exposure, etc.), giving conclusive answer to the question: 'How much performance gain is due to use of a signal prior and how much is due to multiplexing? Our analysis also clearly shows that multiplexing provides significant performance gains above and beyond the gains obtained due to use of signal priors. PMID- 26352625 TI - A MultiScale Particle Filter Framework for Contour Detection. AB - We investigate the contour detection task in complex natural images. We propose a novel contour detection algorithm which jointly tracks at two scales small pieces of edges called edgelets. This multiscale edgelet structure naturally embeds semi local information and is the basic element of the proposed recursive Bayesian modeling. Prior and transition distributions are learned offline using a shape database. Likelihood functions are learned online, thus are adaptive to an image, and integrate color and gradient information via local, textural, oriented, and profile gradient-based features. The underlying model is estimated using a sequential Monte Carlo approach, and the final soft contour detection map is retrieved from the approximated trajectory distribution. We also propose to extend the model to the interactive cut-out task. Experiments conducted on the Berkeley Segmentation data sets show that the proposed MultiScale Particle Filter Contour Detector method performs well compared to competing state-of-the-art methods. PMID- 26352626 TI - Active Learning by Querying Informative and Representative Examples. AB - Active learning reduces the labeling cost by iteratively selecting the most valuable data to query their labels. It has attracted a lot of interests given the abundance of unlabeled data and the high cost of labeling. Most active learning approaches select either informative or representative unlabeled instances to query their labels, which could significantly limit their performance. Although several active learning algorithms were proposed to combine the two query selection criteria, they are usually ad hoc in finding unlabeled instances that are both informative and representative. We address this limitation by developing a principled approach, termed QUIRE, based on the min max view of active learning. The proposed approach provides a systematic way for measuring and combining the informativeness and representativeness of an unlabeled instance. Further, by incorporating the correlation among labels, we extend the QUIRE approach to multi-label learning by actively querying instance label pairs. Extensive experimental results show that the proposed QUIRE approach outperforms several state-of-the-art active learning approaches in both single label and multi-label learning. PMID- 26352627 TI - Autonomous Document Cleaning--A Generative Approach to Reconstruct Strongly Corrupted Scanned Texts. AB - We study the task of cleaning scanned text documents that are strongly corrupted by dirt such as manual line strokes, spilled ink, etc. We aim at autonomously removing such corruptions from a single letter-size page based only on the information the page contains. Our approach first learns character representations from document patches without supervision. For learning, we use a probabilistic generative model parameterizing pattern features, their planar arrangements and their variances. The model's latent variables describe pattern position and class, and feature occurrences. Model parameters are efficiently inferred using a truncated variational EM approach. Based on the learned representation, a clean document can be recovered by identifying, for each patch, pattern class and position while a quality measure allows for discrimination between character and non-character patterns. For a full Latin alphabet we found that a single page does not contain sufficiently many character examples. However, even if heavily corrupted by dirt, we show that a page containing a lower number of character types can efficiently and autonomously be cleaned solely based on the structural regularity of the characters it contains. In different example applications with different alphabets, we demonstrate and discuss the effectiveness, efficiency and generality of the approach. PMID- 26352628 TI - Batch-Orthogonal Locality-Sensitive Hashing for Angular Similarity. AB - Sign-random-projection locality-sensitive hashing (SRP-LSH) is a widely used hashing method, which provides an unbiased estimate of pairwise angular similarity, yet may suffer from its large estimation variance. We propose in this work batch-orthogonal locality-sensitive hashing (BOLSH), as a significant improvement of SRP-LSH. Instead of independent random projections, BOLSH makes use of batch-orthogonalized random projections, i.e, we divide random projection vectors into several batches and orthogonalize the vectors in each batch respectively. These batch-orthogonalized random projections partition the data space into regular regions, and thus provide a more accurate estimator. We prove theoretically that BOLSH still provides an unbiased estimate of pairwise angular similarity, with a smaller variance for any angle in (0, pi), compared with SRP LSH. Furthermore, we give a lower bound on the reduction of variance. The extensive experiments on real data well validate that with the same length of binary code, BOLSH may achieve significant mean squared error reduction in estimating pairwise angular similarity. Moreover, BOLSH shows the superiority in extensive approximate nearest neighbor (ANN) retrieval experiments. PMID- 26352629 TI - Block-Sparse RPCA for Salient Motion Detection. AB - Recent evaluation [2], [13] of representative background subtraction techniques demonstrated that there are still considerable challenges facing these methods. Challenges in realistic environment include illumination change causing complex intensity variation, background motions (trees, waves, etc.) whose magnitude can be greater than those of the foreground, poor image quality under low light, camouflage, etc. Existing methods often handle only part of these challenges; we address all these challenges in a unified framework which makes little specific assumption of the background. We regard the observed image sequence as being made up of the sum of a low-rank background matrix and a sparse outlier matrix and solve the decomposition using the Robust Principal Component Analysis method. Our contribution lies in dynamically estimating the support of the foreground regions via a motion saliency estimation step, so as to impose spatial coherence on these regions. Unlike smoothness constraint such as MRF, our method is able to obtain crisply defined foreground regions, and in general, handles large dynamic background motion much better. Furthermore, we also introduce an image alignment step to handle camera jitter. Extensive experiments on benchmark and additional challenging data sets demonstrate that our method works effectively on a wide range of complex scenarios, resulting in best performance that significantly outperforms many state-of-the-art approaches. PMID- 26352630 TI - Classemes and Other Classifier-Based Features for Efficient Object Categorization. AB - This paper describes compact image descriptors enabling accurate object categorization with linear classification models, which offer the advantage of being efficient to both train and test. The shared property of our descriptors is the use of classifiers to produce the features of each image. Intuitively, these classifiers evaluate the presence of a set of basis classes inside the image. We first propose to train the basis classifiers as recognizers of a hand-selected set of object classes. We then demonstrate that better accuracy can be achieved by learning the basis classes as "abstract categories" collectively optimized as features for linear classification. Finally, we describe several strategies to aggregate the outputs of basis classifiers evaluated on multiple subwindows of the image in order to handle cases when the photo contains multiple objects and large amounts of clutter. We test our descriptors on challenging benchmarks of object categorization and detection, using a simple linear SVM as classifier. Our results are on par with those achieved by the best systems in these fields but are produced at orders of magnitude lower computational costs and using an image representation that is general and not specifically tuned for a predefined set of test classes. PMID- 26352631 TI - Fast Compressive Tracking. AB - It is a challenging task to develop effective and efficient appearance models for robust object tracking due to factors such as pose variation, illumination change, occlusion, and motion blur. Existing online tracking algorithms often update models with samples from observations in recent frames. Despite much success has been demonstrated, numerous issues remain to be addressed. First, while these adaptive appearance models are data-dependent, there does not exist sufficient amount of data for online algorithms to learn at the outset. Second, online tracking algorithms often encounter the drift problems. As a result of self-taught learning, misaligned samples are likely to be added and degrade the appearance models. In this paper, we propose a simple yet effective and efficient tracking algorithm with an appearance model based on features extracted from a multiscale image feature space with data-independent basis. The proposed appearance model employs non-adaptive random projections that preserve the structure of the image feature space of objects. A very sparse measurement matrix is constructed to efficiently extract the features for the appearance model. We compress sample images of the foreground target and the background using the same sparse measurement matrix. The tracking task is formulated as a binary classification via a naive Bayes classifier with online update in the compressed domain. A coarse-to-fine search strategy is adopted to further reduce the computational complexity in the detection procedure. The proposed compressive tracking algorithm runs in real-time and performs favorably against state-of-the art methods on challenging sequences in terms of efficiency, accuracy and robustness. PMID- 26352632 TI - High Dimensional Semiparametric Scale-Invariant Principal Component Analysis. AB - We propose a new high dimensional semiparametric principal component analysis (PCA) method, named Copula Component Analysis (COCA). The semiparametric model assumes that, after unspecified marginally monotone transformations, the distributions are multivariate Gaussian. COCA improves upon PCA and sparse PCA in three aspects: (i) It is robust to modeling assumptions; (ii) It is robust to outliers and data contamination; (iii) It is scale-invariant and yields more interpretable results. We prove that the COCA estimators obtain fast estimation rates and are feature selection consistent when the dimension is nearly exponentially large relative to the sample size. Careful experiments confirm that COCA outperforms sparse PCA on both synthetic and real-world data sets. PMID- 26352633 TI - Adaptive Linear Regression for Appearance-Based Gaze Estimation. AB - We investigate the appearance-based gaze estimation problem, with respect to its essential difficulty in reducing the number of required training samples, and other practical issues such as slight head motion, image resolution variation, and eye blinking. We cast the problem as mapping high-dimensional eye image features to low-dimensional gaze positions, and propose an adaptive linear regression (ALR) method as the key to our solution. The ALR method adaptively selects an optimal set of sparsest training samples for the gaze estimation via l(1)-optimization. In this sense, the number of required training samples is significantly reduced for high accuracy estimation. In addition, by adopting the basic ALR objective function, we integrate the gaze estimation, subpixel alignment and blink detection into a unified optimization framework. By solving these problems simultaneously, we successfully handle slight head motion, image resolution variation and eye blinking in appearance-based gaze estimation. We evaluated the proposed method by conducting experiments with multiple users and variant conditions to verify its effectiveness. PMID- 26352634 TI - Kernelized Bayesian Matrix Factorization. AB - We extend kernelized matrix factorization with a full-Bayesian treatment and with an ability to work with multiple side information sources expressed as different kernels. Kernels have been introduced to integrate side information about the rows and columns, which is necessary for making out-of-matrix predictions. We discuss specifically binary output matrices but extensions to realvalued matrices are straightforward. We extend the state of the art in two key aspects: (i) A full-conjugate probabilistic formulation of the kernelized matrix factorization enables an efficient variational approximation, whereas full-Bayesian treatments are not computationally feasible in the earlier approaches. (ii) Multiple side information sources are included, treated as different kernels in multiple kernel learning which additionally reveals which side sources are informative. We then show that the framework can also be used for supervised and semi-supervised multilabel classification and multi-output regression, by considering samples and outputs as the domains where matrix factorization operates. Our method outperforms alternatives in predicting drug-protein interactions on two data sets. On multilabel classification, our algorithm obtains the lowest Hamming losses on 10 out of 14 data sets compared to five state-of-the-art multilabel classification algorithms. We finally show that the proposed approach outperforms alternatives in multi-output regression experiments on a yeast cell cycle data set. PMID- 26352635 TI - Sparse Feature Extraction for Pose-Tolerant Face Recognition. AB - Automatic face recognition performance has been steadily improving over years of research, however it remains significantly affected by a number of factors such as illumination, pose, expression, resolution and other factors that can impact matching scores. The focus of this paper is the pose problem which remains largely overlooked in most real-world applications. Specifically, we focus on one to-one matching scenarios where a query face image of a random pose is matched against a set of gallery images. We propose a method that relies on two fundamental components: (a) A 3D modeling step to geometrically correct the viewpoint of the face. For this purpose, we extend a recent technique for efficient synthesis of 3D face models called 3D Generic Elastic Model. (b) A sparse feature extraction step using subspace modeling and l1-minimization to induce pose-tolerance in coefficient space. This in return enables the synthesis of an equivalent frontal-looking face, which can be used towards recognition. We show significant performance improvements in verification rates compared to commercial matchers, and also demonstrate the resilience of the proposed method with respect to degrading input quality. We find that the proposed technique is able to match non-frontal images to other non-frontal images of varying angles. PMID- 26352636 TI - Statistical Inverse Ray Tracing for Image-Based 3D Modeling. AB - This paper proposes a new formulation and solution to image-based 3D modeling (aka "multi-view stereo") based on generative statistical modeling and inference. The proposed new approach, named statistical inverse ray tracing, models and estimates the occlusion relationship accurately through optimizing a physically sound image generation model based on volumetric ray tracing. Together with geometric priors, they are put together into a Bayesian formulation known as Markov random field (MRF) model. This MRF model is different from typical MRFs used in image analysis in the sense that the ray clique, which models the ray tracing process, consists of thousands of random variables instead of two to dozens. To handle the computational challenges associated with large clique size, an algorithm with linear computational complexity is developed by exploiting, using dynamic programming, the recursive chain structure of the ray clique. We further demonstrate the benefit of exact modeling and accurate estimation of the occlusion relationship by evaluating the proposed algorithm on several challenging data sets. PMID- 26352637 TI - StructBoost: Boosting Methods for Predicting Structured Output Variables. AB - Boosting is a method for learning a single accurate predictor by linearly combining a set of less accurate weak learners. Recently, structured learning has found many applications in computer vision. Inspired by structured support vector machines (SSVM), here we propose a new boosting algorithm for structured output prediction, which we refer to as StructBoost. StructBoost supports nonlinear structured learning by combining a set of weak structured learners. As SSVM generalizes SVM, our StructBoost generalizes standard boosting approaches such as AdaBoost, or LPBoost to structured learning. The resulting optimization problem of StructBoost is more challenging than SSVM in the sense that it may involve exponentially many variables and constraints. In contrast, for SSVM one usually has an exponential number of constraints and a cutting-plane method is used. In order to efficiently solve StructBoost, we formulate an equivalent 1-slack formulation and solve it using a combination of cutting planes and column generation. We show the versatility and usefulness of StructBoost on a range of problems such as optimizing the tree loss for hierarchical multi-class classification, optimizing the Pascal overlap criterion for robust visual tracking and learning conditional random field parameters for image segmentation. PMID- 26352638 TI - Structured Labels in Random Forests for Semantic Labelling and Object Detection. AB - Ensembles of randomized decision trees, known as Random Forests, have become a valuable machine learning tool for addressing many computer vision problems. Despite their popularity, few works have tried to exploit contextual and structural information in random forests in order to improve their performance. In this paper, we propose a simple and effective way to integrate contextual information in random forests, which is typically reflected in the structured output space of complex problems like semantic image labelling. Our paper has several contributions: We show how random forests can be augmented with structured label information and be used to deliver structured low-level predictions. The learning task is carried out by employing a novel split function evaluation criterion that exploits the joint distribution observed in the structured label space. This allows the forest to learn typical label transitions between object classes and avoid locally implausible label configurations. We provide two approaches for integrating the structured output predictions obtained at a local level from the forest into a concise, global, semantic labelling. We integrate our new ideas also in the Hough-forest framework with the view of exploiting contextual information at the classification level to improve the performance on the task of object detection. Finally, we provide experimental evidence for the effectiveness of our approach on different tasks: Semantic image labelling on the challenging MSRCv2 and CamVid databases, reconstruction of occluded handwritten Chinese characters on the Kaist database and pedestrian detection on the TU Darmstadt databases. PMID- 26352639 TI - CuI/Oxalic Diamide Catalyzed Coupling Reaction of (Hetero)Aryl Chlorides and Amines. AB - A class of oxalic diamides are found to be effective ligands for promoting CuI catalyzed aryl amination with less reactive (hetero)aryl chlorides. The reaction proceeds at 120 degrees C with K3PO4 as the base in DMSO to afford a wide range of (hetero)aryl amines in good to excellent yields. The bis(N-aryl) substituted oxalamides are superior ligands to N-aryl-N'-alkyl substituted or bis(N-alkyl) substituted oxalamides. Both the electronic nature and the steric property of the aromatic rings in ligands are important for their efficiency. PMID- 26352640 TI - Fe-Catalyzed Reductive Coupling of Unactivated Alkenes with beta-Nitroalkenes. AB - An Fe-catalyzed reductive coupling of unactivated alkenes with beta-nitroalkenes has been developed. The reaction proceeds through a radical pathway, with beta nitroalkenes serving as the vinylating reagents and the nitro group being cleaved in the process. Therefore, this method provides a viable synthetic approach to valuable secondary- and tertiary-alkylated styrene derivatives. Furthermore, control experiments were conducted and a plausible mechanism is proposed. PMID- 26352641 TI - Canadian high risk endometrial cancer (CHREC) consortium: analyzing the clinical behavior of high risk endometrial cancers. AB - OBJECTIVES: The objective of this study is to analyze the clinical behavior of endometrial carcinomas by high risk(HR) histotype, including stage, overall survival, recurrence free survival and patterns of failure. METHODS: This is a retrospective multi-institutional cohort study performed at 7 tertiary care centers across Canada between 2000 and 2012 and included: grade 3 endometrioid (EC3), endometrial serous cancer (ESC), clear cell carcinomas (CCC) and carcinosarcoma (CS). Clinicopathological and outcome data was collected. RESULTS: 1260 women with endometrial carcinoma with 1013 having staging procedures were identified; 398 EC3, 449 ESC, 236 CS and 91 CCC. 51.8% had lymphovascular space invasion (LVSI) and 18.5% had omental involvement with a statistically significant difference between tumor types (p=0.0005 and 0.0047 respectively); ESC had a significantly greater rate of omental involvement compared to EC3 (22% to 9%, p=0.0005). Within the entire cohort 49.3% were stage 1, 10.6% were stage 2, 27.4% were stage 3 and 12.7% were stage 4. Overall survival and recurrence free survival were significantly different between histotypes (p<0.0001) with CS having the worst outcome. Overall 31.5% of patients recurred. CS and ESC had a higher distant recurrence rate compared to EC3 (29.6%, 31.0% compared to 16.4%, p=0.0002 and p<0.001). CONCLUSION: This study is one of the largest clinical cohorts of HR endometrial cancers. We have further clarified the impact of histotype and stage on recurrence and survival, and the high likelihood of distant recurrence. However, the differences are modest and risk prediction models will require additional molecular markers. PMID- 26352642 TI - In Nonobese Girls, Waist Circumference as a Predictor of Insulin Resistance Is Comparable to MRI Fat Measures and Superior to BMI. AB - OBJECTIVE: The aim of this study was to investigate the degree to which waist circumference (WC), body mass index (BMI), and magnetic resonance imaging (MRI) measured abdominal fat deposition predict insulin resistance (IR) in nonobese girls of diverse racial and ethnic backgrounds. METHODS: Fifty-seven nonobese girls (12 African-American, 16 Hispanic White, and 29 non-Hispanic White girls) aged 11-14 years were assessed for WC, MRI hepatic proton density fat fraction, visceral and subcutaneous adipose tissue volume, BMI Z-score, fasting insulin, homeostasis model of assessment (HOMA)-IR, adiponectin, leptin, sex hormone binding globulin, high-density lipoprotein cholesterol, and triglycerides. RESULTS: Univariate and multivariate analyses adjusted for race and ethnicity indicated that only WC and visceral adipose tissue volume were independent predictors of fasting insulin and HOMA-IR, while hepatic proton density fat fraction, BMI Z-score, and subcutaneous adipose tissue volume were dependent predictors. Hispanic White girls showed significantly higher mean fasting insulin and HOMA-IR and lower sex hormone-binding globulin than non-Hispanic White girls (p < 0.01). CONCLUSIONS: In nonobese girls of diverse racial and ethnic backgrounds, WC, particularly when adjusted for race or ethnicity, is an independent predictor of IR comparable to MRI-derived measurements of fat and superior to the BMI Z-score. PMID- 26352643 TI - Modeling and evaluation of urban pollution events of atmospheric heavy metals from a large Cu-smelter. AB - Metal smelting and processing are highly polluting activities that have a strong influence on the levels of heavy metals in air, soil, and crops. We employ an atmospheric transport and dispersion model to predict the pollution levels originated from the second largest Cu-smelter in Europe. The model predicts that the concentrations of copper (Cu), zinc (Zn), and arsenic (As) in an urban area close to the Cu-smelter can reach 170, 70, and 30 ng m-3, respectively. The model captures all the observed urban pollution events, but the magnitude of the elemental concentrations is predicted to be lower than that of the observed values; ~300, ~500, and ~100 ng m-3 for Cu, Zn, and As, respectively. The comparison between model and observations showed an average correlation coefficient of 0.62 +/- 0.13. The simulation shows that the transport of heavy metals reaches a peak in the afternoon over the urban area. The under-prediction in the peak is explained by the simulated stronger winds compared with monitoring data. The stronger simulated winds enhance the transport and dispersion of heavy metals to the regional area, diminishing the impact of pollution events in the urban area. This model, driven by high resolution meteorology (2 km in horizontal), predicts the hourly-interval evolutions of atmospheric heavy metal pollutions in the close by urban area of industrial hotspot. PMID- 26352644 TI - Mapping soil organic carbon content using spectroscopic and environmental data: A case study in acidic soils from NW Spain. AB - In this study we present a methodology to estimate and map the content of soil organic carbon (SOC) in topsoils using spectroscopic (FTIR-ATR) and environmental raster data. We determined the SOC content in 221 topsoil samples in Galicia (NW Spain) using the Walkley-Black method. FTIR-ATR spectroscopic data was measured upon the same set of samples. The Random Forest (RF) technique was used to link the measured SOC concentrations to the FTIR-ATR measurements in order to identify the relevant absorbance bands explaining most of the variability in SOC. We then used linear regression (MLR) to predict SOC concentrations from the selected FTIR ATR bands as independent proxy. This model showed a good predictive performance (r-squared=0.88; RSME=2.14; ME=0.05; RPD=3.14), indicating that SOC can be effectively estimated from the identified spectral bands. Finally, we used Partial Least Squares (PLS) to model the spatial distribution of the predictor bands using a number of environmental raster maps (climate, land use and geology) as covariates. This new raster was used within the MLR model previously created to generalize the predictions of SOC in the whole study area. This approach shows that FTIR data can be used to map SOC while minimizing analytical costs and time efforts. PMID- 26352645 TI - Mercury (II) reduction and co-precipitation of metallic mercury on hydrous ferric oxide in contaminated groundwater. AB - Mercury (Hg) speciation and sorption analyses in contaminated aquifers are useful for understanding transformation, retention, and mobility of Hg in groundwater. In most aquifers hydrous ferric oxides (HFOs) are among the most important sorbents for trace metals; however, their role in sorption or mobilization of Hg in aquifers has been rarely analyzed. In this study, we investigated Hg chemistry and Hg sorption to HFO under changing redox conditions in a highly HgCl2 contaminated aquifer (up to 870MUgL(-1) Hg). Results from aqueous and solid phase Hg measurements were compared to modeled (PHREEQC) data. Speciation analyses of dissolved mercury indicated that Hg(II) forms were reduced to Hg(0) under anoxic conditions, and adsorbed to or co-precipitated with HFO. Solid phase Hg thermo desorption measurements revealed that between 55 and 93% of Hg bound to HFO was elemental Hg (Hg(0)). Hg concentrations in precipitates reached more than 4 weight %, up to 7000 times higher than predicted by geochemical models that do not consider unspecific sorption to and co-precipitation of elemental Hg with HFO. The observed process of Hg(II) reduction and Hg(0) formation, and its retention and co-precipitation by HFO is thought to be crucial in HgCl2 contaminated aquifers with variable redox-conditions regarding the related decrease in Hg solubility (factor of ~10(6)), and retention of Hg in the aquifer. PMID- 26352646 TI - Environmental impacts of various biomass supply chains for the provision of raw wood in Bavaria, Germany, with focus on climate change. AB - Wood biomass is considered a renewable raw product, but the supply chain of wood biomass involves non-renewable energy inputs, and thus possibly entailing environmental impacts. The objective of this study was to analyze different environmental impacts (GHG emissions, without biogenic CO2; primary energy consumption, non-renewable; particulate matter) caused by the provision of forest biomass for the four main tree species in Bavaria using Life Cycle Assessment (LCA) techniques. Based on forest growth simulations, a set of realistic forest biomass supply chains for Bavarian forestry conditions were modeled for the raw wood product system from site preparation to forest road and to plant/farm gate, respectively, analyzing the four different process groups: [A1] site preparation, [A2] site tending, [A3] biomass harvesting and [T] transport of biomass to plant/farm gate. Total GHG emissions of about 383,000tCO2-eq*year(-1) (18.95kgCO2 eq*m(-3)) are estimated for the Bavarian forestry sector (from site preparation to plant/farm gate) in the reference year 2013 indicating a share of 0.41% in the total GHG emissions of Bavaria. 0.035MJ of non-renewable energy has to be invested in order to provide 1MJ of woody biomass to plant/farm gate (267MJ*m( 3)). One hundred and sixty six tons of particulate matter emissions per year are calculated for the Bavarian forestry sector in 2013 (0.008kgPM2.5-eq*m(-3)). Our LCA results reveal that there is no single GHG emission value for raw wood but a broad range of possible GHG emissions for the Bavarian forestry. Most decisive parameters are forest road maintenance, biomass harvesting, forwarding and biomass transport, and GHG emissions are also notably influenced by tree species, age class, wood assortment and site quality. We recommend that environmental impact calculations should be implemented, for example in wood certification procedures as they are important key indicators for sustainable forest management. PMID- 26352647 TI - De novo sequencing and variant calling with nanopores using PoreSeq. AB - The accuracy of sequencing single DNA molecules with nanopores is continually improving, but de novo genome sequencing and assembly using only nanopore data remain challenging. Here we describe PoreSeq, an algorithm that identifies and corrects errors in nanopore sequencing data and improves the accuracy of de novo genome assembly with increasing coverage depth. The approach relies on modeling the possible sources of uncertainty that occur as DNA transits through the nanopore and finds the sequence that best explains multiple reads of the same region. PoreSeq increases nanopore sequencing read accuracy of M13 bacteriophage DNA from 85% to 99% at 100* coverage. We also use the algorithm to assemble Escherichia coli with 30* coverage and the lambda genome at a range of coverages from 3* to 50*. Additionally, we classify sequence variants at an order of magnitude lower coverage than is possible with existing methods. PMID- 26352648 TI - Supramolecular Assembly of Complementary Cyanine Salt J-Aggregates. AB - An understanding of structure-property relationships in cyanine dyes is critical for their design and application. Anionic and cationic cyanines can be organized into complementary cyanine salts, offering potential building blocks to modulate their intra/intermolecular interactions in the solid state. Here, we demonstrate how the structures of these complementary salts can be tuned to achieve highly ordered J-type supramolecular aggregate structures of heptamethine dyes in crystalline solids. PMID- 26352651 TI - Overcoming Obstacles. PMID- 26352650 TI - Comparative efficacy of antiviral therapy in preventing vertical transmission of hepatitis B: a network meta-analysis. AB - BACKGROUND & AIMS: Antiviral drugs are safe and effective in the third trimester to prevent intrauterine transmission of hepatitis B virus, and are recommended for hepatitis B virus (HBV) infected gravid mothers (between weeks 28 and 32) with high viral load, followed by postnatal hepatitis B immunization in the newborn. We estimated the comparative efficacy of antiviral drugs for prevention of vertical transmission of HBV, through a network meta-analysis of clinical trials. METHODS: We conducted a comprehensive search of MEDLINE, EMBASE and published proceedings from major liver meetings from January 1980 to November 2014. We conducted pair-wise meta-analyses and Bayesian framework using Markov chain Monte Carlo methods, combining direct and indirect evidence for any given pair of treatments. RESULTS: Seventeen clinical trials involving 2764 newborns of hepatitis B surface antigen seropositive mothers were eligible for analysis. There were no clinical trials involving tenofovir or entecavir. On pair-wise meta analyses, telbivudine (hazard ratio, HR 0.12, 95% confidence interval (CI) 0.04 0.37; I(2) = 0%), and Lamivudine (HR 0.40, 95% CI 0.24-0.65; I(2) = 0%), were more effective than placebo in reducing vertical transmission of HBV in high viremic hepatitis B e antigen (HBeAg)-positive chronic Hepatitis B Chinese patients. Sensitivity analyses limited to studies with HBeAg seropositive mothers revealed similar results. CONCLUSIONS: Based on a Bayesian network meta-analysis of clinical trials, combining direct and indirect treatment comparisons, telbivudine appears to be more effective than Lamivudine for preventing vertical transmission of HBV infection. Trials assessing the efficacy of tenofovir or entecavir compared to placebo or other antiviral drugs are lacking. PMID- 26352652 TI - Do We Have Leaders Among Us? PMID- 26352653 TI - Bridges and Barriers: Patients' Perceptions of the Discharge Process Including Multidisciplinary Rounds on a Trauma Unit. AB - Discharge planning is a complex process and ideally begins early in the patient stay. Despite evidence about the importance of discharge readiness, there is limited literature about the patient's view during this transition. The goal of this study was to explore patient perspectives about the discharge process, including multidisciplinary rounds. Multidisciplinary rounding is a process where care providers from various specialties meet to communicate, coordinate patient care, make decisions, and manage responsibilities. The theme found was "bridges and barriers to discharge." Participants identified timelines and tasks, communication, social support, and motivation as helpful and medical setbacks, insurance limitations, and infrequent communication as hindrances to the discharge. Future research is recommended examining efficacy of various discharge models and examination of communication and support throughout hospitalization. PMID- 26352654 TI - Emergency Preparedness Education for Nurses: Core Competency Familiarity Measured Utilizing an Adapted Emergency Preparedness Information Questionnaire. AB - The purpose of this project was to measure trauma nurse improvement in familiarity with emergency preparedness and disaster response core competencies as originally defined by the Emergency Preparedness Information Questionnaire after a focused educational program. An adapted version of the Emergency Preparedness Information Questionnaire was utilized to measure familiarity of nurses with core competencies pertinent to first responder capabilities. This project utilized a pre- and postsurvey descriptive design and integrated education sessions into the preexisting, mandatory "Trauma Nurse Course" at large, level I trauma center. A total of 63 nurses completed the intervention during May and September 2014 sessions. Overall, all 8 competencies demonstrated significant (P < .001; 98% confidence interval) improvements in familiarity. In conclusion, this pilot quality improvement project demonstrated a unique approach to educating nurses to be more ready and comfortable when treating victims of a disaster. PMID- 26352655 TI - Trauma Patients' Family Members' Perceptions of Nurses' Caring Behaviors. AB - A mixed methods study was conducted to identify trauma patients' family members' perceptions of nurses' caring behaviors on a trauma step-down unit at a level I trauma center. Family members completed Caring Behaviors Inventory-Short Form 24 and a qualitative section. Quantitative data were analyzed using descriptive statistics. On a scale of 1 to 6, the mean score for individual items was 5.2 (median = 5.3). Participants considered the nurses' behaviors to be indicative of caring in each of the 4 areas measured-assurance, knowledge/skills, respectfulness, and connectedness. Four themes were identified-technical, nonverbal, personal connections, and addressing comfort. PMID- 26352656 TI - Use of an Electronic C-Spine Clearance Strategy to Ensure Compliance With Confrontational Examinations: A Performance Improvement Patient Safety Project. AB - The implementation of electronic medical records (EMRs) represents one of the most significant changes taking place in the medical field today. The purpose of this Performance Improvement Patient Safety initiative was to evaluate and improve the documentation of c-spine clearances by standardizing the confrontational spine examination for patients sustaining blunt trauma using the EMR. A retrospective audit of trauma charts was performed over a 6-month period to evaluate c-spine clearance documentation. Following the initial audit, a strategy, using the Donabedian Principle of problem identification, process establishment, and outcome measure, was created resulting in a template in the EMR whereby clearance of the cervical spine (confrontational examination) in nonobtunded trauma patients was standardized for all providers. Outcomes before and after implementation of the EMR protocol were compared. The initial audit revealed that 71% of records lacked appropriate documentation. Of those with documentation, 26% simply stated "c-spine cleared" or "collar removed" with no documentation to support the clinical examination performed. This is in contrast to a 95% compliance rate following the use of the EMR protocol. Up to 80% of collars were removed within 3 hours of admission thereby reducing complications associated with c-collars. The use of the EMR allowed for the standardization of the cervical spine clearance, improved documentation, and allowed for the monitoring of compliance with evidenced-based c-spine protocols. Practice implications and lessons learned in the implementation of this successful Performance Improvement Patient Safety are also described. PMID- 26352657 TI - Palliative Medicine Consultation Reduces Length of Stay, Improves Symptom Management, and Clarifies Advance Directives in the Geriatric Trauma Population. AB - The impact of Palliative Medicine Consultation (PMC) on geriatric trauma patients' outcomes was evaluated. It was hypothesized that patients with PMC would have a shorter length of stay. Patients aged 65 years or older and admitted to trauma services were analyzed. Patients with a PMC were more likely to have a documented advance directive discussion (P < .001) and a code status update (P < .001). Length of stay was reduced for patients with a PMC on or before trauma day 2 compared to those with a PMC after trauma day 2. Palliative Medicine should be consulted early into a geriatric patient's hospital stay. PMID- 26352658 TI - Blueprint for Implementing New Processes in Acute Care: Rescuing Adult Patients With Intraosseous Access. AB - The intraosseous (IO) access initiative at an urban university adult level 1 trauma center began from the need for a more expeditious vascular access route to rescue patients in extremis. The goal of this project was a multidisciplinary approach to problem solving to increase access of IO catheters to rescue patients in all care areas. The initiative became a collaborative effort between nursing, physicians, and pharmacy to embark on an acute care endeavor to standardize IO access. This is a descriptive analysis of processes to effectively develop collaborative strategies to navigate hospital systems and successfully implement multilayered initiatives. Administration should empower nurse to advance their practice to include IO for patient rescue. Intraosseous access may expedite resuscitative efforts in patients in extremis who lack venous access or where additional venous access is required for life-saving therapies. Limiting IO dwell time may facilitate timely definitive venous access. Continued education and training by offering IO skill laboratory refreshers and annual e-learning didactic is optimal for maintaining proficiency and knowledge. More research opportunities exist to determine medication safety and efficacy in adult patients in the acute care setting. PMID- 26352659 TI - The Lack of Common Goals and Communication Within a Level I Trauma System: Assessing the Silo Effect Among Trauma Center Employees. AB - We assessed our level I trauma center's employees' perception of inter- and intradepartmental relationships to determine whether employees who work less often with patients feel less involved-the silo effect. We prospectively evaluated employees who provide direct patient care using the Trauma System Survey tool. Of 1155 employees, 699 responded. Combined interdepartmental relationships showed that 93% believed their unit communicated well with other units, and 86% thought other units communicated well with their unit. However, 69% experienced miscommunication between units. To reduce silos, communication is key. Training and multiunit events may help reduce these silos further. PMID- 26352660 TI - Designing Technology to Decrease Pneumonia in Intubated Trauma Patients. AB - Trauma patients are at increased risk for developing ventilator-associated pneumonia. Sixty adult trauma intensive care unit patients were audited 3 months prepractice change, and 30 were audited postpractice change. Quality improvement interventions included staff education of a redesigned electronic medical record ventilator bundle and chlorhexidine gluconate administration timing practice change. Postpractice change audits revealed 2-hour chlorhexidine gluconate documentation increased from 38.3% to 73.3% and incidence of pneumonia in intubated patients decreased by 62%. Early initiation of chlorhexidine gluconate mouth care utilizing electronic medical record technology may help reduce pneumonia in intubated patients, hospital length of stay, overall health costs, and improve documentation. PMID- 26352661 TI - Birthplace of ATLS Becomes New Teaching Site for ATCN. PMID- 26352664 TI - Feathers as a Tool to Assess Mercury Contamination in Gentoo Penguins: Variations at the Individual Level. AB - Feathers have been widely used to assess mercury contamination in birds as they reflect metal concentrations accumulated between successive moult periods: they are also easy to sample and have minimum impact on the study birds. Moult is considered the major pathway for mercury excretion in seabirds. Penguins are widely believed to undergo a complete, annual moult during which they do not feed. As penguins lose all their feathers, they are expected to have a low individual-variability in feather mercury concentration as all feathers are formed simultaneously from the same somatic reserves. This assumption is central to penguin studies that use feathers to examine the annual or among-individual variation in mercury concentrations in penguins. To test this assumption, we measured the mercury concentrations in 3-5 body feathers of 52 gentoo penguins (Pygoscelis papua) breeding at Bird Island, South Georgia (54 degrees S 38 degrees W). Twenty-five percent of the penguins studied showed substantial within individual variation in the amount of mercury in their feathers (Coefficient of Variation: 34.7-96.7%). This variation may be caused by differences in moult patterns among individuals within the population leading to different interpretations in the overall population. Further investigation is now needed to fully understand individual variation in penguins' moult. PMID- 26352665 TI - In the Right Place at the Right Time: Is TMC1/2 the Transduction Channel for Hearing? AB - Recent papers suggest that TMC1 and TMC2 constitute the ion channels mediating hearing and balance. Kurima et al. (2015) now show these proteins are expressed in the right place and at the right time, bringing us closer to definitive identification. PMID- 26352666 TI - Enrolling patients into genomically matched clinical trials found challenging. PMID- 26352667 TI - Use of Hyperspectral Imagery to Assess Cryptic Color Matching in Sargassum Associated Crabs. AB - Mats of the pelagic macroalgae Sargassum represent a complex environment for the study of marine camouflage at the air-sea interface. Endemic organisms have convergently evolved similar colors and patterns, but quantitative assessments of camouflage strategies are lacking. Here, spectral camouflage of two crab species (Portunus sayi and Planes minutus) was assessed using hyperspectral imagery (HSI). Crabs matched Sargassum reflectance across blue and green wavelengths (400 550 nm) and diverged at longer wavelengths. Maximum discrepancy was observed in the far-red (i.e., 675 nm) where Chlorophyll a absorption occurred in Sargassum and not the crabs. In a quantum catch color model, both crabs showed effective color matching against blue/green sensitive dichromat fish, but were still discernible to tetrachromat bird predators that have visual sensitivity to far red wavelengths. The two species showed opposing trends in background matching with relation to body size. Variation in model parameters revealed that discrimination of crab and background was impacted by distance from the predator, and the ratio of cone cell types for bird predators. This is one of the first studies to detail background color matching in this unique, challenging ecosystem at the air-sea interface. PMID- 26352668 TI - The bifunctional MU opioid agonist/antioxidant [Dmt(1)]DALDA is a superior analgesic in an animal model of complex regional pain syndrome-type i. AB - Reactive oxygen species (ROS) play an important role in the development of complex regional pain syndrome-Type I (CRPS-I), as also demonstrated with the chronic post ischemia pain (CPIP) animal model of CRPS-I. We show that morphine and the antioxidant N-acetylcysteine (NAC) act synergistically to reduce mechanical allodynia in CPIP rats. The tetrapeptide amide [Dmt(1)]DALDA (H-Dmt-d Arg-Phe-Lys-NH2) is a potent and selective MU opioid receptor (MOR) agonist with favorable pharmacokinetic properties and with antioxidant activity due to its N terminal Dmt (2',6'-dimethyltyrosine) residue. In the CPIP model, [Dmt(1)]DALDA was 15-fold more potent than morphine in reversing mechanical allodynia and 4.5 fold more potent as analgesic in the heat algesia test. The results indicate that bifunctional compounds with MOR agonist/antioxidant activity have therapeutic potential for the treatment of CRPS-I. PMID- 26352669 TI - Outer Hair Cell Lateral Wall Structure Constrains the Mobility of Plasma Membrane Proteins. AB - Nature's fastest motors are the cochlear outer hair cells (OHCs). These sensory cells use a membrane protein, Slc26a5 (prestin), to generate mechanical force at high frequencies, which is essential for explaining the exquisite hearing sensitivity of mammalian ears. Previous studies suggest that Slc26a5 continuously diffuses within the membrane, but how can a freely moving motor protein effectively convey forces critical for hearing? To provide direct evidence in OHCs for freely moving Slc26a5 molecules, we created a knockin mouse where Slc26a5 is fused with YFP. These mice and four other strains expressing fluorescently labeled membrane proteins were used to examine their lateral diffusion in the OHC lateral wall. All five proteins showed minimal diffusion, but did move after pharmacological disruption of membrane-associated structures with a cholesterol-depleting agent and salicylate. Thus, our results demonstrate that OHC lateral wall structure constrains the mobility of plasma membrane proteins and that the integrity of such membrane-associated structures are critical for Slc26a5's active and structural roles. The structural constraint of membrane proteins may exemplify convergent evolution of cellular motors across species. Our findings also suggest a possible mechanism for disorders of cholesterol metabolism with hearing loss such as Niemann-Pick Type C diseases. PMID- 26352670 TI - Angiopoietin-Like-4, a Potential Target of Tacrolimus, Predicts Earlier Podocyte Injury in Minimal Change Disease. AB - Podocyte injury plays central roles in proteinuria and kidney dysfunction, therefore, identifying specific biomarker to evaluate earlier podocyte injury is highly desirable. Podocyte-secreted angiopoietin-like-4 (Angptl4) mediates proteinuria in different types of podocytopathy. In the present study, we established an experimental minimal change disease (MCD) rat model, induced by adriamycin (ADR) and resulted in definite podocyte injury, to identify the dynamic changes in Angptl4 expression. We also investigated the direct effects of tacrolimus on Angptl4 and podocyte repair. We determined that the glomerular Angptl4 expression was rapidly upregulated and reached a peak earlier than desmin, an injured podocyte marker, in the ADR rats. Furthermore, this upregulation occurred prior to heavy proteinuria and was accompanied by increased urinary Angptl4. We observed that the Angptl4 upregulation occurred only when podocyte was mainly damaged since we didn't observe little Angptl4 upregulation in MsPGN patients. In addition, we observed the glomerular Angptl4 mainly located in injured podocytes rather than normal podocytes. Moreover, we found that tacrolimus treatment significantly promoted podocyte repair and reduced glomerular and urinary Angptl4 expression at an earlier stage with a significant serum Angptl4 upregulation. And similar results were confirmed in MCD patients. In conclusion, this study represents the first investigation to demonstrate that Angptl4 can predict podocyte injury at earlier stages in MCD and the identification of earlier podocyte injury biomarkers could facilitate the prompt diagnosis and treatment of patients with podocytopathy, as well as determination of the prognosis and treatment efficacy in these diseases. PMID- 26352671 TI - Whole-Genome Analysis of Diversity and SNP-Major Gene Association in Peach Germplasm. AB - Peach was domesticated in China more than four millennia ago and from there it spread world-wide. Since the middle of the last century, peach breeding programs have been very dynamic generating hundreds of new commercial varieties, however, in most cases such varieties derive from a limited collection of parental lines (founders). This is one reason for the observed low levels of variability of the commercial gene pool, implying that knowledge of the extent and distribution of genetic variability in peach is critical to allow the choice of adequate parents to confer enhanced productivity, adaptation and quality to improved varieties. With this aim we genotyped 1,580 peach accessions (including a few closely related Prunus species) maintained and phenotyped in five germplasm collections (four European and one Chinese) with the International Peach SNP Consortium 9K SNP peach array. The study of population structure revealed the subdivision of the panel in three main populations, one mainly made up of Occidental varieties from breeding programs (POP1OCB), one of Occidental landraces (POP2OCT) and the third of Oriental accessions (POP3OR). Analysis of linkage disequilibrium (LD) identified differential patterns of genome-wide LD blocks in each of the populations. Phenotypic data for seven monogenic traits were integrated in a genome-wide association study (GWAS). The significantly associated SNPs were always in the regions predicted by linkage analysis, forming haplotypes of markers. These diagnostic haplotypes could be used for marker-assisted selection (MAS) in modern breeding programs. PMID- 26352672 TI - Transdifferentiation-Induced Neural Stem Cells Promote Recovery of Middle Cerebral Artery Stroke Rats. AB - Induced neural stem cells (iNSCs) can be directly transdifferentiated from somatic cells. One potential clinical application of the iNSCs is for nerve regeneration. However, it is unknown whether iNSCs function in disease models. We produced transdifferentiated iNSCs by conditional overexpressing Oct4, Sox2, Klf4, c-Mycin mouse embryonic fibroblasts. They expanded readily in vitro and expressed NSC mRNA profile and protein markers. These iNSCs differentiated into mature astrocytes, neurons and oligodendrocytes in vitro. Importantly, they reduced lesion size, promoted the recovery of motor and sensory function as well as metabolism status in middle cerebral artery stroke rats. These iNSCs secreted nerve growth factors, which was associated with observed protection of neurons from apoptosis. Furthermore, iNSCs migrated to and passed through the lesion in the cerebral cortex, where Tuj1+ neurons were detected. These findings have revealed the function of transdifferentiated iNSCs in vivo, and thus provide experimental evidence to support the development of personalized regenerative therapy for CNS diseases by using genetically engineered autologous somatic cells. PMID- 26352673 TI - MicroRNA-132 inhibits cell growth and metastasis in osteosarcoma cell lines possibly by targeting Sox4. AB - Increasing evidence has confirmed that dysregulation of microRNAs (miRNAs) can contribute to the progression and metastasis of human tumors. Previous studies have shown that dysregulation of microRNAs (miRNAs) can contribute to the progression and metastasis of human tumors. However, the precise mechanisms of miR-132 in osteosarcoma have not been well clarified. Real-time PCR was performed to detect the expression of miR-132 in osteosarcoma cell lines. miR-132 mimic, miR-132 inhibitor and negative control were transfected into osteosarcoma cells and the effects of miR-132 on the cell growth and metastasis were investigated. Furthermore, protein level of Sox4 was measured by western blotting. Luciferase assays were performed to validate Sox4 as miR-132 target in osteosarcoma cells. We found that miR-132 was downregulated in osteosarcoma cell lines. Introduction of miR-132 significantly inhibited proliferation, arrested cell cycle and induced apoptosis in osteosarcoma cells. Besides, invasion and epithelial-mesenchymal transition (EMT) of osteosarcoma cells was suppressed by overexpressing miR-132. However, downregulation of miR-132 promoted cell growth and metastasis in osteosarcoma cells. Bioinformatics analysis predicted that Sox4 was a potential target gene of miR-132. Luciferase reporter assay demonstrated that miR-132 could directly target Sox4. Moreover, the low level of miR-132 was associated with increased expression of Sox4 in osteosarcoma cells. Sox4 inhibition suppressed cell malignant behaviors. Overexpression of Sox4 in osteosarcoma cells transfected with miR-132 mimic partially reversed the inhibitory effect of miR 132. In conclusion, miR-132 inhibited cell growth and metastasis in osteosarcoma cells by downregulation of Sox4, and knockdown of Sox4 was essential for the miR 132-inhibited cell growth and metastasis in osteosarcoma cells. PMID- 26352674 TI - Synthesis and biological evaluation of novel 4,5-disubstituted 2H-1,2,3-triazoles as cis-constrained analogues of combretastatin A-4. AB - A series of combretastatin A-4 (CA-4) analogues have been prepared from (Z) substituted diarylacrylonitriles (1a-1p) obtained in a two-step synthesis from appropriate arylaldehydes and acrylonitriles. The resulting 4,5-disubstituted 2H 1,2,3-triazoles were evaluated for their anti-cancer activities against a panel of 60 human cancer cell lines. The diarylacrylonitrile analogue 2l exhibited the most potent anti-cancer activity in the screening studies, with GI50 values of <10 nM against almost all the cell lines in the human cancer cell panel and TGI values of <10 nM against cancer cell lines SF-539, MDA-MB-435, OVCAR-3 and A498. Furthermore, in silico docking studies of compounds 2l, 2e and 2h within the active site of tubulin were carried out in order to rationalize the mechanism of the anti-cancer properties of these compounds. From the in silico studies, compound 2e was predicted to have better affinity for the colchicine binding site on tubulin compared to compounds 2l and 2h. Analogue 2e was also evaluated for its anti-cancer activity by colony formation assay against 9LSF rat gliosarcoma cells and afforded an LD50 of 7.5 nM. A cell cycle redistribution assay using analogue 2e was conducted to further understand the mechanism of action of these CA-4 analogues. From this study, analogues 2e and 2l were the most potent anti cancer agents in this structural class, and were considered lead compounds for further development as anti-cancer drugs. PMID- 26352675 TI - Novel aminotetrazole derivatives as selective STAT3 non-peptide inhibitors. AB - The development of inhibitors blocking STAT3 transcriptional activity is a promising therapeutic approach against cancer and inflammatory diseases. In this context, the selectivity of inhibitors against the STAT1 transcription factor is crucial as STAT3 and STAT1 play opposite roles in the apoptosis of tumor cells and polarization of the immune response. A structure-based virtual screening followed by a luciferase-containing promoter assay on STAT3 and STAT1 signaling were used to identify a selective STAT3 inhibitor. An important role of the aminotetrazole group in modulating STAT3 and STAT1 inhibitory activities has been established. Optimization of the hit compound leads to 23. This compound inhibits growth and survival of cells with STAT3 signaling pathway while displaying a minimal effect on STAT1 signaling. Moreover, it prevents lymphocyte T polarization into Th17 and Treg without affecting their differentiation into Th1 lymphocyte. PMID- 26352676 TI - Cyclic alpha-conotoxin peptidomimetic chimeras as potent GLP-1R agonists. AB - Type 2 diabetes mellitus (T2DM) results from compromised pancreatic beta-cell function, reduced insulin production, and lowered insulin sensitivity in target organs resulting in hyperglycemia. The GLP-1 hormone has two biologically active forms, GLP-1-(7-37) and GLP-1-(7-36)amide, which are equipotent at the glucagon like peptide-1 receptor (GLP-1R). These peptides are central both to normal glucose metabolism and dysregulation in T2DM. Several structurally modified GLP-1 analogues are now approved drugs, and a number of other analogues are in clinical trials. None of these compounds is orally bioavailable and all require parenteral delivery. Recently, a number of smaller peptidomimetics containing 11-12 natural and unnatural amino acids have been identified that have similar insulin regulating profiles as GLP-1. The alpha-conotoxins are a class of disulfide rich peptide venoms isolated from cone snails, and are known for their highly constrained structures and resistance to enzymatic degradation. In this study, we examined whether 11-residue peptidomimetics incorporated into alpha-conotoxin scaffolds, forming monocyclic or bicyclic compounds constrained by disulfide bonds and/or backbone cyclization, could activate the GLP-1 receptor (GLP-1R). Several compounds showed potent (nanomolar) agonist activity at GLP-1R, as evaluated via cAMP signaling. In addition, HPLC retention times and in silico calculations suggested that mono- and bicyclic compounds had more favorable n octanol/water partition coefficients according to the virtual partition coefficient model (vLogP), while maintaining a smaller radius of gyration compared to corresponding uncyclized peptidomimetics. Our findings suggest that cyclic peptidomimetics provide a potential avenue for future design of potent, compact ligands targeting GLP-1R and possessing improved physicochemical properties. PMID- 26352677 TI - Novel 2H-chromen-2-one derivatives of resveratrol: Design, synthesis, modeling and use as human monoamine oxidase inhibitors. AB - Using a fragment-based drug design strategy, two biomedical interesting fragments, resveratrol and coumarin were linked to design a series of novel human monoamine oxidase (hMAO) inhibitors with a scaffold of 3-((E)-3-(2-((E) styryl)phenyl)acryloyl)-2H-chromen-2-one, which demonstrated a very interesting selectivity profile against hMAO-A and hMAO-B: some compounds with this scaffold are selective hMAO-A inhibitors, whereas some are selective hMAO-B inhibitors. The small changes in the substituents of the coumarin moiety led to this interesting selectivity profile. The most potent selective hMAO-B inhibitor D7 has a selectivity ratio of 20.93, with an IC50 value of 2.78 MUM, similar or better than selegiline (IC50 = 2.89 MUM), a selective hMAO-B inhibitor currently in the market for the treatment of Parkinson's disease. Our modeling study indicates that Tyr 326 of hMAO-B (or corresponded Ile 335 of hMAO-A) may be the determinant for the specificity of these compounds. The selectivity profile of compounds reported herein suggests that we can further develop both selective hMAO-A and hMAO-B inhibitors based on this novel scaffold. PMID- 26352678 TI - Histone H3K4 trimethylation: dynamic interplay with pre-mRNA splicing. AB - Histone H3 lysine 4 trimethylation (H3K4me3) is often stated as a mark of transcriptionally active promoters. However, closer study of the positioning of H3K4me3 shows the mark locating primarily after the first exon at the 5' splice site and overlapping with a CpG island in mammalian cells. There are several enzyme complexes that are involved in the placement of the H3K4me3 mark, including multiple protein complexes containing SETD1A, SETD1B, and MLL1 enzymes (writers). CXXC1, which is associated with SETD1A and SETD1B, target these enzymes to unmethylated CpG islands. Lysine demethylases (KDM5 family members, erasers) demethylate H3K4me3. The H3K4me3 mark is recognized by several proteins (readers), including lysine acetyltransferase complexes, chromatin remodelers, and RNA bound proteins involved in pre-mRNA splicing. Interestingly, attenuation of H3K4me3 impacts pre-mRNA splicing, and inhibition of pre-mRNA splicing attenuates H3K4me3. PMID- 26352679 TI - Enhanced electron spin rotation in CdS quantum dots. AB - We studied the spin rotation of electrons in CdS quantum dots (QDs) and CdS QDs with charge acceptors by means of time-resolved Faraday rotation (TRFR) at room temperature. The electron spin rotation had an oscillatory component in the TRFR signal and the oscillation frequency proportional to the magnetic field gave a g factor of the electrons of 1.965 +/- 0.006. The non-oscillatory component came from the population of excitons and showed an additional decay in CdS QDs with hole acceptors. The electron spin rotation signal was largely enhanced and lasted for a spin coherence time of T2* = 450 ps in CdS QDs tethered to TiO2 electron acceptors, where the spin initialization was triggered by the positive trion transition. These results give clear evidence that the electron spin rotation signal in QDs can be enhanced by transient p-doping. PMID- 26352681 TI - Low Rate of Perinatal Sepsis in Term Infants of Mothers with Chorioamnionitis. AB - OBJECTIVE: The risk of infection in infants of mothers with chorioamnionitis (CAM) may be lower than previously reported. This study's objective was to determine the incidence of intrapartum fever (IPF) and culture-positive early onset bacterial neonatal infection (CPEOI) in the late preterm and term infants of mothers with or without CAM and to assess interhospital variation in neonatal infection management. STUDY DESIGN: This retrospective cohort study included mothers and newborns delivered at >=35 weeks gestation at Kaiser Permanente Southern California Hospitals in 2010 (n = 31,112). Electronic medical and laboratory records from 13 medical centers were examined for maternal temperature, intrapartum, and neonatal antibiotic treatment. Rates for IPF, CAM, and CPEOI were estimated. Rates for starting neonatal antibiotics were calculated. RESULTS: The incidence of IPF was 9% and CAM 4%. The overall rate for CPEOI was 0.61/1,000 (95% confidence interval [CI] 0.34, 0.89/1,000). The rate of CPEOI was 4.0/1,000 (95% CI 0.50, 7.5/1,000) in infants born to mothers with CAM. The rate of beginning antibiotics for infants born to mothers with CAM ranged from 7 to 76% between nurseries. CONCLUSION: The rate of CPEOI in infants born to mothers with CAM is lower than previously reported. There is heterogeneity in initiation of neonatal antibiotics by neonatologists. PMID- 26352682 TI - Does Induction with Misoprostol Impact the Small for Gestational Age Neonate? AB - OBJECTIVE: To compare outcomes in small for gestational age neonates induced with misoprostol to other cervical ripening agents. We hypothesized that misoprostol use will demonstrate no significant difference in outcomes compared with alternative agents. STUDY DESIGN: Small for gestational age neonates (<10th percentile for gestational age) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) sponsored Consortium on Safe Labor database were analyzed. Neonates induced with misoprostol +/- oxytocin (n = 451) were compared with neonates induced with prostaglandin E2 +/- oxytocin and/or mechanical dilation +/- oxytocin (n = 663). Primary outcomes included intrapartum fetal distress, cesarean section for fetal distress, cesarean section for any reason, neonatal intensive care unit admission, low 5-minute Apgar, and composite neonatal morbidity. Multiple logistic regression was used to calculate adjusted odds ratios (aORs). Data were analyzed using SAS. RESULTS: Small for gestational age neonates induced with misoprostol +/- oxytocin compared with alternative agents had decreased low 5-minute Apgar scores (aOR 0.27 [0.10 0.71]). No significant differences were demonstrated among very small for gestational age neonates (<5th percentile for gestational age). CONCLUSION: Our results suggest that misoprostol does not increase risk of adverse outcomes in small for gestational age neonates; however, prospective studies are warranted to further assess optimal cervical ripening agents in this population. PMID- 26352683 TI - Newborns Referred for Therapeutic Hypothermia: Association between Initial Degree of Encephalopathy and Severity of Brain Injury (What About the Newborns with Mild Encephalopathy on Admission?). AB - OBJECTIVE: The aim of this article was to describe the severity of brain injury and/or mortality in a cohort of newborns referred for therapeutic hypothermia, in relation to the degree of encephalopathy on admission, and to especially look at the ones with initial mild encephalopathy. STUDY DESIGN: Term newborns with perinatal depression referred to our neonatal intensive care unit for possible hypothermia treatment from 2008 to 2012 were enrolled prospectively. The modified Sarnat score on admission was correlated with severity of brain injury on brain imaging and/or autopsy. RESULTS: A total of 215 newborns were referred for possible cooling. Sixty percent (128/215) were cooled. Most of the not-cooled newborns with an available brain magnetic resonance imaging (85% = 50/59) had an initial mild encephalopathy, and 40% (20/50) developed brain injury. Some cooled newborns had an initial mild encephalopathy (12% = 13/108); only 31% (4/13) developed brain injury. CONCLUSION: Our results demonstrated that several newborns with an initial mild encephalopathy developed subsequent brain injury, especially when they were not cooled. PMID- 26352680 TI - Relationship of Early Pregnancy Waist-to-Hip Ratio versus Body Mass Index with Gestational Diabetes Mellitus and Insulin Resistance. AB - OBJECTIVE: To determine the risk of gestational diabetes mellitus (GDM) and insulin resistance (IR) in obesity defined by body mass index (BMI), waist-to-hip ratio (WHR), or both combined. METHODS: Secondary analysis of a randomized multicenter trial of antioxidant supplementation versus placebo in nulliparous low-risk women to prevent pregnancy associated hypertension. Women between 9 and 16 weeks with data for WHR and BMI were analyzed for GDM (n = 2,300). Those with fasting glucose and insulin between 22 and 26 weeks (n = 717) were analyzed for IR by homeostatic model assessment of IR (normal, <= 75th percentile). WHR and BMI were categorized as normal (WHR, < 0.80; BMI, < 25 kg/m(2)); overweight (WHR, 0.8-0.84; BMI, 25-29.9 kg/m(2)); and obese (WHR, >= 0.85; BMI >= 30 kg/m(2)). Receiver operating characteristic curves and logistic regression models were used. RESULTS: Compared with normal, the risks of GDM or IR were higher in obese by BMI or WHR. The subgroup with obesity by WHR but not by BMI had no increased risk of GDM. BMI was a better predictor of IR (area under the curve [AUC]: 0.71 [BMI], 0.65 [WHR], p = 0.03) but similar to WHR for GDM (AUC: 0.68 [BMI], 0.63 [WHR], p = 0.18). CONCLUSION: Increased WHR and BMI in early pregnancy are associated with IR and GDM. BMI is a better predictor of IR compared with WHR. Adding WHR to BMI does not improve its ability to detect GDM or IR. PMID- 26352684 TI - Fetal Gender of the First Born and the Recurrent Risk of Spontaneous Preterm Birth. AB - OBJECTIVE: To study, in women with a spontaneous preterm birth (sPTB) in the first pregnancy, the effect of fetal sex in that first pregnancy on the recurrent sPTB risk. STUDY DESIGN: A nationwide retrospective cohort study (data from National Perinatal Registry) on all women with two sequential singleton pregnancies (1999-2009) with the first delivery ending in sPTB <37 weeks. We used logistic regression analysis to study the association between fetal gender in the first pregnancy and the risk of recurrent sPTB. We repeated the analysis for sPTB < 32 weeks. RESULTS: The overall incidence of sPTB <37 weeks in the first pregnancy was 4.5% (15,351/343,853). Among those 15,351 women, the risk of recurrent sPTB <37 weeks was increased when the first fetus was female compared when that fetus was male (15.8 vs. 15.2%; adjusted odds ratio [aOR] 1.2; 95% confidence interval [CI] 1.05-1.3). A similar effect was seen for sPTB <32weeks (8.2 vs. 5.9%; aOR 4.5; 95% CI 1.5-13). CONCLUSION: Women who suffer sPTB of a female fetus have an increased risk of recurrent sPTB compared with women who suffer sPTB of a male fetus. This information provides proof for the hypothesis that sPTB is due to an independent maternal and fetal factor. PMID- 26352685 TI - Maternal Obesity Class as a Predictor of Induction Failure: A Practical Risk Assessment Tool. AB - OBJECTIVE: To assess the impact of body mass index (BMI) on the rate of cesarean section (rCS) in induction of labor (IOL). STUDY DESIGN: A total of 7,543 singleton term pregnancies undergoing IOL (cervical dilatation at admission, CDA <= 3 cm) were divided according to BMI: underweight (n = 325); normal weight (NW) (n = 4,633); overweight (OW) (n = 1,610); and obese (n = 975). Age, parity, macrosomia, gestational age (GA), gestational weight gain (GWG), CDA, and IOL indications were considered. RESULTS: A higher rate of macrosomia (15.0 vs. 11.1%; p < 0.0001), earlier induction (GA 39.7 +/- 1.3 vs. 40.1 +/- 1.3 weeks; p < 0.0001) for maternal indications (39.1 vs. 21.1%; p < 0.001), and lower CDA (<=1cm; 66.4 vs. 61.4%; p < 0.005) were observed in obese versus NW. The rate of weight gain above the recommended range was higher in obese (obese 70.6% vs. NW 43.9%; p < 0.001), despite a significantly lower mean GWG compared with NW (14 +/ 7.5 vs. 16.5 +/- 5.6 kg; p < 0.001). Compared with NW, OW and obese demonstrated a significantly higher rCS (OW 31.1% and obese 36.9% vs. NW 24.7%; p < 0.001). BMI represented an independent factor affecting the rCS (vs. NW; OW odds ratio [OR] 1.4; confidence interval [CI] 1.2-1.7; p < 0.001; obese OR 2.3; CI 1.9-2.7 p < 0.001). CONCLUSION: In the case of IOL, obesity represents an independent factor associated with a significant increase of CS to be considered during induction counselling. PMID- 26352687 TI - Investigating the Molecular Basis of Retinal Degeneration in a Familial Cohort of Pakistani Decent by Exome Sequencing. AB - PURPOSE: To define the molecular basis of retinal degeneration in consanguineous Pakistani pedigrees with early onset retinal degeneration. METHODS: A cohort of 277 individuals representing 26 pedigrees from the Punjab province of Pakistan was analyzed. Exomes were captured with commercial kits and sequenced on an Illumina HiSeq 2500. Candidate variants were identified using standard tools and analyzed using exomeSuite to detect all potentially pathogenic changes in genes implicated in retinal degeneration. Segregation analysis was performed by dideoxy sequencing and novel variants were additionally investigated for their presence in ethnicity-matched controls. RESULTS: We identified a total of nine causal mutations, including six novel variants in RPE65, LCA5, USH2A, CNGB1, FAM161A, CERKL and GUCY2D as the underlying cause of inherited retinal degenerations in 13 of 26 pedigrees. In addition to the causal variants, a total of 200 variants each observed in five or more unrelated pedigrees investigated in this study that were absent from the dbSNP, HapMap, 1000 Genomes, NHLBI ESP6500, and ExAC databases were identified, suggesting that they are common in, and unique to the Pakistani population. CONCLUSIONS: We identified causal mutations associated with retinal degeneration in nearly half of the pedigrees investigated in this study through next generation whole exome sequencing. All novel variants detected in this study through exome sequencing have been cataloged providing a reference database of variants common in, and unique to the Pakistani population. PMID- 26352686 TI - Targeting Mutant BRAF in Relapsed or Refractory Hairy-Cell Leukemia. AB - BACKGROUND: BRAF V600E is the genetic lesion underlying hairy-cell leukemia. We assessed the safety and activity of the oral BRAF inhibitor vemurafenib in patients with hairy-cell leukemia that had relapsed after treatment with a purine analogue or who had disease that was refractory to purine analogues. METHODS: We conducted two phase 2, single-group, multicenter studies of vemurafenib (at a dose of 960 mg twice daily)--one in Italy and one in the United States. The therapy was administered for a median of 16 weeks in the Italian study and 18 weeks in the U.S. study. Primary end points were the complete response rate (in the Italian trial) and the overall response rate (in the U.S. trial). Enrollment was completed (28 patients) in the Italian trial in April 2013 and is still open (26 of 36 planned patients) in the U.S. trial. RESULTS: The overall response rates were 96% (25 of 26 patients who could be evaluated) after a median of 8 weeks in the Italian study and 100% (24 of 24) after a median of 12 weeks in the U.S. study. The rates of complete response were 35% (9 of 26 patients) and 42% (10 of 24) in the two trials, respectively. In the Italian trial, after a median follow-up of 23 months, the median relapse-free survival was 19 months among patients with a complete response and 6 months among those with a partial response; the median treatment-free survival was 25 months and 18 months, respectively. In the U.S. trial, at 1 year, the progression-free survival rate was 73% and the overall survival rate was 91%. Drug-related adverse events were usually of grade 1 or 2, and the events most frequently leading to dose reductions were rash and arthralgia or arthritis. Secondary cutaneous tumors (treated with simple excision) developed in 7 of 50 patients. The frequent persistence of phosphorylated ERK-positive leukemic cells in bone marrow at the end of treatment suggests bypass reactivation of MEK and ERK as a resistance mechanism. CONCLUSIONS: A short oral course of vemurafenib was highly effective in patients with relapsed or refractory hairy-cell leukemia. (Funded by the Associazione Italiana per la Ricerca sul Cancro and others; EudraCT number, 2011 005487-13; ClinicalTrials.gov number NCT01711632.). PMID- 26352689 TI - CH3NH3SnxPb1-xBr3 hybrid perovskite solid solution: synthesis, structure, and optical properties. AB - We report the synthesis and characterization of a MASnxPb1-xBr3 (MA = methylammonium; nominal x = 0, 0.2, 0.4, 0.5, 0.6, 0.8, 1) solid solution. The original synthetic method developed allowed one to obtain single-phase materials with homogeneous Sn/Pb distribution. All of the samples prepared are cubic, and the unit cell linearly decreases with increasing x value. The optical response indicates a linear trend (Vegard's law) of the band gap with increasing Sn content from 2.20 eV (x = 0) to 1.33 eV (x = 1), thus extending light absorption into the near-IR. PMID- 26352688 TI - Phenotypic and Genotypic Analysis of Newly Obtained Interspecific Hybrids in the Campanula Genus. AB - Interspecific hybridisation creates new phenotypes within several ornamental plant species including the Campanula genus. We have employed phenotypic and genotypic methods to analyse and evaluate interspecific hybridisation among cultivars of four Campanula species, i.e. C. cochleariifolia, C. isophylla, C. medium and C. formanekiana. Hybrids were analysed using amplified fragment length polymorphism (AFLP), flow cytometry and biometrical measurements. Results of correlation matrices demonstrated heterogeneous phenotypes for the parental species, which confirmed our basic premise for new phenotypes of interspecific hybrids. AFLP assays confirmed the hybridity and identified self-pollinated plants. Limitation of flow cytometry analysis detection was observed while detecting the hybridity status of two closely related parents, e.g. C. cochleariiafolia * C. isophylla. Phenotypic characteristics such as shoot habitus and flower colour were strongly influenced by one of the parental species in most crosses. Rooting analysis revealed that inferior rooting quality occurred more often in interspecific hybrids than in the parental species. Only interspecific hybrid lines of C. formanekiana 'White' * C. medium 'Pink' showed a high rooting level. Phenotype analyses demonstrated a separation from the interspecific hybrid lines of C. formanekiana 'White' * C. medium 'Pink' to the other clustered hybrids of C. formanekiana and C. medium. In our study we demonstrated that the use of correlation matrices is a suitable tool for identifying suitable cross material. This study presents a comprehensive overview for analysing newly obtained interspecific hybrids. The chosen methods can be used as guidance for analyses for further interspecific hybrids in Campanula, as well as in other ornamental species. PMID- 26352690 TI - Variation in stratum corneum protein content as a function of anatomical site and ethnic group. AB - OBJECTIVES: Quantification of stratum corneum (SC) protein levels from tape strippings is frequently used to investigate skin conditions, to correct for amounts of SC protein removed in SC biomarker studies and to determine distribution of topically applied ingredients. In recent years, a rapid and convenient method for SC protein quantification from tape strippings has become available using infrared densitometry (IRD). However, standard curves have only been generated for Caucasian forearm and shoulder SC and have been assumed to be correct not only for facial SC but also for SC samples of other ethnic groups. The aim of this study was to investigate whether the use of IRD for SC protein measurement is valid for other body sites such as the cheek and for measuring SC protein content of darkly pigmented skin types. METHODS: Ten Caucasian and ten Black African female subjects with self-assessed normal skin participated in the study. Tape strippings were collected from two different body sites (forearm and cheek). First from the tape strippings, the SC optical absorption was determined densitometrically. This obtained absorption (%) was compared with absolute SC protein extracted from the same tapes using a colorimetric microbicinchoninic acid (MUBCA) assay. RESULTS: Higher amounts of SC protein were removed from the forearm compared with the cheek (P < 0.01). The absolute SC protein concentration quantified by MUBCA assay and the absorption of SC proteins by IRD followed a similar profile. There was no significant difference found between the two ethnicities in SC protein (P > 0.05). The overall coefficient of determination (R(2) ) shows a good fit to the regression line between the two methods in both sites (forearm = 0.82, cheek = 0.77). Also, both ethnicities showed good correlation (R(2) >= 0.69, P = 0.01). CONCLUSIONS: Facial SC is morphologically distinct from the forearm, as demonstrated by the differences in amounts of SC removed. Although the data distribution in different subject groups varied, the regression was always quite similar between the two body sites and both ethnic groups. Also, the correlations were similar to previously published data on other body sites. The resultant calibration curves can be used as a rapid indirect protein assessment of tape strippings from the cheek. PMID- 26352691 TI - Short-Term Space-Use Patterns of Translocated Mojave Desert Tortoise in Southern California. AB - Increasingly, renewable energy comprises a larger share of global energy production. Across the western United States, public lands are being developed to support renewable energy production. Where there are conflicts with threatened or endangered species, translocation can be used in an attempt to mitigate negative effects. For the threatened Mojave desert tortoise (Gopherus agassizii), we sought to compare habitat- and space-use patterns between short-distance translocated, resident, and control groups. We tested for differences in home range size based on utilization distributions and used linear mixed-effects models to compare space-use intensity, while controlling for demographic and environmental variables. In addition, we examined mean movement distances as well as home range overlap between years and for male and female tortoises in each study group. During the first active season post-translocation, home range size was greater and space-use intensity was lower for translocated tortoises than resident and control groups. These patterns were not present in the second season. In both years, there was no difference in home range size or space-use intensity between control and resident groups. Translocation typically resulted in one active season of questing followed by a second active season characterized by space-use patterns that were indistinguishable from control tortoises. Across both years, the number of times a tortoise was found in a burrow was positively related to greater space-use intensity. Minimizing the time required for translocated tortoises to exhibit patterns similar to non-translocated individuals may have strong implications for conservation by reducing exposure to adverse environmental conditions and predation. With ongoing development, our results can be used to guide future efforts aimed at understanding how translocation strategies influence patterns of animal space use. PMID- 26352692 TI - Anomalies of Imagination and Disordered Self in Schizophrenia Spectrum Disorders. AB - Vivid mental imagery occurs frequently in schizophrenia spectrum disorders (SSDs). Overlapping phenomena, such as obsessions or ruminations, are also frequent in other psychiatric disorders, raising significant diagnostic challenges. Unfortunately, contemporary operational psychopathology lacks the epistemological and phenomenological framework to address such questions. Using the resources of phenomenology and philosophy of mind, we articulate the structure of imagination and describe its distinctive modifications in the SSDs. Drawing on pilot data with patients' self-descriptions, we present the notion of perceptualized imagery. The anomalous imagery acquires spatialization, spatiotemporal constancy, explorability, autonomy and a sense of experiential distance between the subject and the image. As a quasi-perceptual, stable object, such imagery often evokes an intense affective response, whereas the normal sense of 'irreality' of the fantasy may become compromised. We articulate these anomalies of imagination as being entailed by the underlying generative disorder of schizophrenia, namely the disorder of minimal self (unstable ipseity or first person perspective). We propose that pathology of imagination is an important psychopathological aspect of the schizophrenia spectrum, with significant relevance for early diagnosis and differential diagnosis. PMID- 26352693 TI - Genetic Polymorphisms of IL28B and PNPLA3 Are Predictive for HCV Related Rapid Fibrosis Progression and Identify Patients Who Require Urgent Antiviral Treatment with New Regimens. AB - The assessment of individual risk of fibrosis progression in patients with chronic hepatitis C is an unmet clinical need. Recent genome-wide association studies have highlighted several genetic alterations as predictive risk factors of rapid fibrosis progression in chronic hepatitis C. However, most of these results require verification, and whether the combined use of these genetic predictors can assess the risk of fibrosis progression remains unclear. Therefore, genetic risk factors associated with fibrosis progression were analyzed in 176 chronic hepatitis C patients who did not achieve sustained virological response by interferon-based therapy and linked to the fibrosis progression rate (FPR). FPR was determined in all patients by paired liver biopsy performed before and after therapy (mean interval: 6.2 years). Mean FPR in patients with IL28B (rs8099917) TG/GG and PNPLA3 (rs738409) CG/GG were significantly higher than in those with IL28B TT (FPR: 0.144 vs. 0.034, P < 0.001) and PNPLA3 CC (FPR: 0.10 vs. 0.018, P = 0.005), respectively. IL28B TG/GG [hazard ratio (HR): 3.9, P = 0.001] and PNPLA3 CG/GG (HR: 3.1, P = 0.04) remained independent predictors of rapid fibrosis progression upon multivariate analysis together with average alanine aminotransferase after interferon therapy >=40 IU/l (HR: 4.2, P = 0.002). Based on these data, we developed a new clinical score predicting the risk of fibrosis progression (FPR-score). The FPR-score identified subgroups of patients with a low (FPR: 0.005), intermediate (FPR: 0.103, P < 0.001), and high (FPR: 0.197, P < 0.001) risk of fibrosis progression. In conclusion, IL28B and PNPLA3 genotypes are associated with rapid fibrosis progression, and the FPR-score identifies patients who has a high risk of fibrosis progression and require urgent antiviral treatment. PMID- 26352695 TI - Rapid-response fluorescent probe for hydrogen peroxide in living cells based on increased polarity of C-B bonds. AB - Hydrogen peroxide (H2O2) as a reactive oxygen species (ROS) plays a crucial role in oxidative stress and signal transduction of organisms. Currently, a fluorescence probe has proven to be a powerful tool for the H2O2 analysis. However, the common problem is the slow response, causing difficulty in tracking H2O2 in situ. Herein, we describe a novel aggregation-induced emission (AIE) fluorescence probe based on increased polarity of C-B bonds that is well suited for monitoring H2O2 rapidly and selectively. Importantly, the probe was successfully applied to visualize H2O2 levels in living cells, which provides a rapid-response and highly selective fluorescence tool for monitoring of the H2O2 levels in biological process. PMID- 26352696 TI - Collateral Circulation Predicts the Size of the Infarct Core and the Proportion of Salvageable Penumbra in Hyperacute Ischemic Stroke Patients Treated with Intravenous Thrombolysis. AB - BACKGROUND: We studied the impact of collateral circulation on CT perfusion (CTP) parametric maps and the amount of salvaged brain tissue, the imaging and clinical outcome at 24 h and at 3 months in a retrospective acute (<3 h) stroke cohort (105 patients) with anterior circulation thrombus treated with intravenous thrombolysis. METHODS: Baseline clinical and imaging information were collected and groups with different collateral scores (CS) were compared. Binary logistic regression analyses using good CS (CS >=2) as the dependent variable were calculated. RESULTS: CTP Alberta Stroke Program Early CT Score (ASPECTS) was successfully assessed in 58 cases. Thirty patients displayed good CS. Poor CS were associated with more severe strokes according to National Institutes of Health Stroke Scale (NIHSS) at arrival (15 vs. 7, p = 0.005) and at 24 h (10 vs. 3, p = 0.003) after intravenous thrombolysis. Good CS were associated with a longer mean onset-to-treatment time (141 vs. 121 min, p = 0.009) and time to CTP (102 vs. 87 min, p = 0.047), better cerebral blood volume (CBV) ASPECTS (9 vs. 6, p < 0.001), better mean transit time (MTT) ASPECTS (6 vs. 3, p < 0.001), better noncontrast CT (NCCT) ASPECTS (10 vs. 8, p < 0.001) at arrival and with favorable clinical outcome at 3 months (modified Rankin Scale <=2, p = 0.002). The fraction of penumbra that was salvageable at arrival and salvaged at 24 h was higher with better CS (p < 0.001 and p = 0.035, respectively). In multivariate analysis, time from the onset of symptoms to imaging (p = 0.037, OR 1.04 per minute, 95% CI 1.00 1.08) and CBV ASPECTS (p = 0.001, OR 2.11 per ASPECTS point, 95% CI 1.33-3.34) predicted good CS. In similar multivariable models, MTT ASPECTS (p = 0.04, OR 1.46 per ASPECTS point, 95% CI 1.02-2.10) and NCCT ASPECTS predicted good CS (p = 0.003, OR 4.38 per CT ASPECTS point, 95% CI 1.66-11.55) along with longer time from the onset of symptoms to imaging (p = 0.045, OR 1.03 per minute, 95% CI 1.00 1.06 and p = 0.02, OR 1.05 per minute, 95% CI 1.00-1.09, respectively). CBV ASPECTS had a larger area under the receiver operating characteristic curve for good CS (0.837) than NCCT ASPECTS (0.802) or MTT ASPECTS (0.752) at arrival. CONCLUSIONS: Favorable CBV ASPECTS, NCCT ASPECTS and MTT ASPECTS are associated with good CS along with more salvageable tissue and longer time from the onset of symptoms to imaging in ischemic stroke patients treated with intravenous thrombolysis. PMID- 26352694 TI - Effect of Delirium and Other Major Complications on Outcomes After Elective Surgery in Older Adults. AB - IMPORTANCE: Major postoperative complications and delirium contribute independently to adverse outcomes and high resource use in patients who undergo major surgery; however, their interrelationship is not well examined. OBJECTIVE: To evaluate the association of major postoperative complications and delirium, alone and combined, with adverse outcomes after surgery. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study in 2 large academic medical centers of 566 patients who were 70 years or older without recognized dementia or a history of delirium and underwent elective major orthopedic, vascular, or abdominal surgical procedures with a minimum 3-day hospitalization between June 18, 2010, and August 8, 2013. Data analysis took place from December 13, 2013, through May 1, 2015. MAIN OUTCOMES AND MEASURES: Major postoperative complications, defined as life altering or life-threatening events (Accordion Severity grade 2 or higher), were identified by expert-panel adjudication. Delirium was measured daily with the Confusion Assessment Method and a validated medical record review method. The following 4 subgroups were analyzed: (1) no complications or delirium; (2) complications only; (3) delirium only; and (4) complications and delirium. Adverse outcomes included a length of stay (LOS) of more than 5 days, institutional discharge, and rehospitalization within 30 days of discharge. RESULTS: In the 566 participants, the mean (SD) age was 76.7 (5.2) years, 236 (41.7%) were male, and 523 (92.4%) were white. Forty-seven patients (8.3%) developed major complications and 135 (23.9%) developed delirium. Compared with no complications or delirium as the reference group, major complications only contributed to prolonged LOS only (relative risk [RR], 2.8; 95% CI, 1.9-4.0); by contrast, delirium only significantly increased all adverse outcomes, including prolonged LOS (RR, 1.9; 95% CI, 1.4-2.7), institutional discharge (RR, 1.5; 95% CI, 1.3-1.7), and 30-day readmission (RR, 2.3; 95% CI, 1.4-3.7). The subgroup with complications and delirium had the highest rates of all adverse outcomes, including prolonged LOS (RR, 3.4; 95% CI, 2.3-4.8), institutional discharge (RR, 1.8; 95% CI, 1.4-2.5), and 30-day readmission (RR, 3.0; 95% CI, 1.3-6.8). Delirium exerted the highest attributable risk at the population level (5.8%; 95% CI, 4.7-6.8) compared with all other adverse events (prolonged LOS, institutional discharge, or readmission). CONCLUSIONS AND RELEVANCE: Major postoperative complications and delirium are separately associated with adverse events and demonstrate a combined effect. Delirium occurs more frequently and has a greater effect at the population level than other major complications. PMID- 26352697 TI - Long-term efficacy of a rural community-based integrated intervention for prevention and management of chronic obstructive pulmonary disease: a cluster randomized controlled trial in China's rural areas. AB - This study aimed to assess the efficacy of a rural community-based integrated intervention for early prevention and management of chronic obstructive pulmonary disease (COPD) in China. This 18-year cluster-randomized controlled trial encompassing 15 villages included 1008 patients (454 men and 40 women in the intervention group [mean age, 54 +/- 10 years]; 482 men and 32 women in the control group [mean age, 53 +/- 10 years]) with confirmed COPD or at risk for COPD. Villages were randomly assigned to the intervention or the control group, and study participants residing within the villages received treatment accordingly. Intervention group patients took part in a program that included systematic health education, smoking cessation counseling, and education on management of COPD. Control group patients received usual care. The groups were compared after 18 years regarding the incidence of COPD, decline in lung function, and mortality of COPD. COPD incidence was lower in the intervention group than in the control group (10% vs 16%, <0.05). A decline in lung function was also significantly delayed in the intervention group compared to the control group of COPD and high-risk patients. The intervention group showed significant improvement in smoking cessation compared with the control group, and smokers in the intervention group had lower smoking indices than in the control group (350 vs 450, <0.05). The intervention group also had a significantly lower cumulative COPD-related death rate than the control group (37% vs 47%, <0.05). A rural community-based integrated intervention is effective in reducing the incidence of COPD among those at risk, delaying a decline in lung function in COPD patients and those at risk, and reducing mortality of COPD. PMID- 26352698 TI - Hyaluronidases and hyaluronan synthases expression is inversely correlated with malignancy in lung/bronchial pre-neoplastic and neoplastic lesions, affecting prognosis. AB - We collected a series of 136 lung/bronchial and 56 matched lung parenchyma tissue samples from patients who underwent lung/bronchial biopsies and presented invasive carcinoma after lung surgery. The lung/bronchial samples included basal cell hyperplasia, squamous metaplasia, moderate dysplasia, adenomatous hyperplasia, severe dysplasia, squamous cell carcinoma and adenocarcinoma. Matched lung parenchyma tissue samples included 25 squamous cell carcinomas and 31 adenocarcinomas. Immunohistochemistry was performed to analyze for the distribution of hyaluronidase (Hyal)-1 and -3, and hyaluronan synthases (HAS)-1, 2, and -3. Hyal-1 showed significantly higher expression in basal cell hyperplasia than in moderate dysplasia (P=0.01), atypical adenomatous hyperplasia (P=0.0001), or severe dysplasia (P=0.03). Lower expression of Hyal-3 was found in atypical adenomatous hyperplasia than in basal cell hyperplasia (P=0.01) or moderate dysplasia (P=0.02). HAS-2 was significantly higher in severe dysplasia (P=0.002) and in squamous metaplasia (P=0.04) compared with basal cell hyperplasia. HAS-3 was significantly expressed in basal cell hyperplasia compared with atypical adenomatous hyperplasia (P=0.05) and severe dysplasia (P=0.02). Lower expression of HAS-3 was found in severe dysplasia compared with squamous metaplasia (P=0.01) and moderate dysplasia (P=0.01). Epithelial Hyal-1 and -3 and HAS-1, -2, and -3 expressions were significantly higher in pre-neoplastic lesions than in neoplastic lesions. Comparative Cox multivariate analysis controlled by N stage and histologic tumor type showed that patients with high HAS-3 expression in pre-neoplastic cells obtained by lung/bronchial biopsy presented a significantly higher risk of death (HR=1.19; P=0.04). We concluded that localization of Hyal and HAS in lung/bronchial pre-neoplastic and neoplastic lesions was inversely related to malignancy, which implied that visualizing these factors could be a useful diagnostic procedure for suspected lung cancer. Finalizing this conclusion will require a wider study in a randomized and prospective trial. PMID- 26352699 TI - Biochemical and Structural Insights into the Mechanism of DNA Recognition by Arabidopsis ETHYLENE INSENSITIVE3. AB - Gaseous hormone ethylene regulates numerous stress responses and developmental adaptations in plants by controlling gene expression via transcription factors ETHYLENE INSENSITIVE3 (EIN3) and EIN3-Like1 (EIL1). However, our knowledge regarding to the accurate definition of DNA-binding domains (DBDs) within EIN3 and also the mechanism of specific DNA recognition by EIN3 is limited. Here, we identify EIN3 82-352 and 174-306 as the optimal and core DBDs, respectively. Results from systematic biochemical analyses reveal that both the number of EIN3 binding sites (EBSs) and the spacing length between two EBSs affect the binding affinity of EIN3; accordingly, a new DNA probe which has higher affinity with EIN3 than ERF1 is also designed. Furthermore, we show that palindromic repeat sequences in ERF1 promoter are not necessary for EIN3 binding. Finally, we provide, to our knowledge, the first crystal structure of EIN3 core DBD, which contains amino acid residues essential for DNA binding and signaling. Collectively, these data suggest the detailed mechanism of DNA recognition by EIN3 and provide an in-depth view at molecular level for the transcriptional regulation mediated by EIN3. PMID- 26352700 TI - Uncovering Cryptic Parasitoid Diversity in Horismenus (Chalcidoidea, Eulophidae). AB - Horismenus parasitoids are an abundant and understudied group of eulophid wasps found mainly in the New World. Recent surveys based on morphological analyses in Costa Rica have quadrupled the number of named taxa, with more than 400 species described so far. This recent revision suggests that there is still a vast number of unknown species to be identified. As Horismenus wasps have been widely described as parasitoids of insect pests associated with crop plants, it is of high importance to properly establish the extant diversity of the genus, in order to provide biological control practitioners with an exhaustive catalog of putative control agents. In this study, we first collected Horismenus wasps from wild Phaseolus bean seeds in Central Mexico and Arizona to assess the genetic relatedness of three morphologically distinct species with overlapping host and geographical ranges. Sequence data from two nuclear and two mitochondrial gene regions uncovered three cryptic species within each of the three focal species (i.e., H. missouriensis, H. depressus and H. butcheri). The monophyly of each cryptic group is statistically supported (except in two of them represented by one single tip in which monophyly cannot be tested). The phylogenetic reconstruction is discussed with respect to differences between gene regions as well as likely reasons for the differences in variability between species. PMID- 26352701 TI - Temporal and Spatial Comparisons of Underwater Sound Signatures of Different Reef Habitats in Moorea Island, French Polynesia. AB - As environmental sounds are used by larval fish and crustaceans to locate and orientate towards habitat during settlement, variations in the acoustic signature produced by habitats could provide valuable information about habitat quality, helping larvae to differentiate between potential settlement sites. However, very little is known about how acoustic signatures differ between proximate habitats. This study described within- and between-site differences in the sound spectra of five contiguous habitats at Moorea Island, French Polynesia: the inner reef crest, the barrier reef, the fringing reef, a pass and a coastal mangrove forest. Habitats with coral (inner, barrier and fringing reefs) were characterized by a similar sound spectrum with average intensities ranging from 70 to 78 dB re 1 MUPa.Hz(-1). The mangrove forest had a lower sound intensity of 70 dB re 1 MUPa.Hz(-1) while the pass was characterized by a higher sound level with an average intensity of 91 dB re 1 MUPa.Hz(-1). Habitats showed significantly different intensities for most frequencies, and a decreasing intensity gradient was observed from the reef to the shore. While habitats close to the shore showed no significant diel variation in sound intensities, sound levels increased at the pass during the night and barrier reef during the day. These two habitats also appeared to be louder in the North than in the West. These findings suggest that daily variations in sound intensity and across-reef sound gradients could be a valuable source of information for settling larvae. They also provide further evidence that closely related habitats, separated by less than 1 km, can differ significantly in their spectral composition and that these signatures might be typical and conserved along the coast of Moorea. PMID- 26352702 TI - The Impact of a Cognitive Behavioral Pain Management Program on Sleep in Patients with Chronic Pain: Results of a Pilot Study. AB - OBJECTIVE: To determine the impact of a cognitive behavioral pain management program on sleep in patients with chronic pain. DESIGN: Prospective nonrandomized controlled pilot study with evaluations at baseline and 12 weeks. SETTING: Out patient multidisciplinary cognitive behavioral pain management program in a university teaching hospital. SUBJECTS: Patients with chronic pain who fulfilled the criteria for participation in a cognitive behavioral pain management program. METHODS: Patients assigned to the intervention group (n = 24) completed a 4 week cognitive behavioral pain management program, and were compared with a waiting list control group (n = 22). Assessments for both groups occurred at baseline and two months post cognitive behavioral pain management program. Outcome measures included self-report (Pittsburgh Sleep Quality Index) and objective (actigraphy) sleep measures, pain and quality of life measures. RESULTS: Both groups were comparable at baseline, and all had sleep disturbance. The Pittsburgh Sleep Quality Index correlated with only two of the seven objective sleep measures (fragmentation index r = 0.34, P = 0.02, and sleep efficiency percentage r = 0.31, P = 0.04). There was a large treatment effect for cognitive behavioral pain management program group in mean number of wake bouts (d = 0.76), where a significant group*time interaction was also found (P = 0.016), showing that the CBT-PMP group improved significantly more than controls in this sleep variable. CONCLUSIONS: Patients attending a cognitive behavioral pain management program have high prevalence of sleep disturbance, and actigraphy technology was well tolerated by the patients. Preliminary analysis of the impact of a cognitive behavioral pain management program on sleep is promising, and warrants further investigation. PMID- 26352704 TI - The Rose review of NHS leadership: better leadership for tomorrow. PMID- 26352703 TI - Enhancement of Performance and Mechanism Studies of All-Solution Processed Small Molecule based Solar Cells with an Inverted Structure. AB - Both solution-processed polymers and small molecule based solar cells have achieved PCEs over 9% with the conventional device structure. However, for the practical applications of photovoltaic technology, further enhancement of both device performance and stability are urgently required, particularly for the inverted structure devices, since this architecture will probably be most promising for the possible coming commercialization. In this work, we have fabricated both conventional and inverted structure devices using the same small molecular donor/acceptor materials and compared the performance of both device structures, and found that the inverted structure based device gave significantly improved performance, the highest PCE so far for inverted structure based device using small molecules as the donor. Furthermore, the inverted device shows a remarkable stability with almost no obvious degradation after three months. Systematic device physics and charge generation dynamics studies, including optical simulation, light-intensity-dependent current-voltage experiments, photocurrent density-effective voltage analyses, transient absorption measurements, and electrical simulations, indicate that the significantly enhanced performance using inverted device is ascribed to the increasing of Jsc compared to the conventional device, which in turn is mainly attributed to the increased absorption of photons in the active layers, rather than the reduced nongeminate recombination. PMID- 26352706 TI - Clinical News. PMID- 26352705 TI - The problem with emergency laparotomies. PMID- 26352707 TI - European Society of Cardiology Congress London, Uk, 29 August-2 September. PMID- 26352708 TI - Family satisfaction with care on the ICU: essential lessons for all doctors. AB - In the intensive care unit (ICU), satisfaction with the care of their loved one impacts upon family members' psychological morbidity and maybe the health of patients afterwards. Enhancing family satisfaction is holistic and may impact on health throughout the hospital and beyond. PMID- 26352709 TI - Redesigning incident reporting systems in the post-Mid-Staffordshire era. AB - Incident reporting systems are vital to safe health care. Existing systems should be made simpler and more accessible, proper feedback given to those who complete reports and lessons learned from investigations shared more widely. A major shift in culture is required so health-care professionals feel safe completing incident reports. PMID- 26352710 TI - Lasting power of attorney: a significant ethical responsibility. AB - A lasting power of attorney makes decisions for another person who lacks the capacity to make the decision him-/herself. There are significant ethical issues which must be considered, not only so that the decision made is morally robust but also so that the individuals entrusted with this responsibility are adequately supported. PMID- 26352711 TI - Infantile haemangioma: their presentation and management. AB - Haemangiomas are the commonest type of vascular tumour in infancy. This article summarizes the pathophysiology and classification of the subtypes as early identification of high-risk lesions is essential for consideration of treatment to prevent short- and long-term complications from the condition. PMID- 26352712 TI - Iron deficiency: still under-diagnosed? AB - Anaemia resulting from iron deficiency is one of the commonest diseases affecting humankind. Although its diagnosis and management may be straightforward, iron deficiency is underdiagnosed in nations with structured health-care systems, mainly because of a lack of awareness of its existence in selected clinical scenarios. PMID- 26352713 TI - Anaesthesia for the changing obstetric population: challenges and solutions. AB - This article outlines the main challenges facing the obstetric anaesthetist as a result of the changing obstetric population and identifies some solutions which may help overcome such challenges in the future. PMID- 26352714 TI - The learning curve of electronic prescribing. AB - INTRODUCTION: Medication errors are a potentially avoidable source of harm to patients. The authors' hospital has introduced electronic prescribing in an attempt to reduce these errors. A prospective quality improvement project was performed to assess both the impact of this change on prescribing errors and to see if there was a learning curve associated with prescribers using the new system. METHODS: A simple prescribing task was created in which study participants were asked to prescribe a set list of medications for a fictional patient. The participants were timed first using paper drug cards, and then using the prescribing function on iSOFT's iClinical Manager. The prescriptions were also assessed for legibility and errors. This was done within 1 week of the participants starting in the department, and then 2 and 4 months later. A total of 25 junior doctors completed the task. No participant had prior experience of electronic prescribing in a clinical setting. RESULTS: During week one, the task took a longer average time to complete using electronic prescribing compared to paper (323 seconds vs 290 seconds, P<0.01). After 2 months the mean time to complete the task was shorter with electronic prescribing compared to paper (261 seconds vs 306 seconds, P<0.01). There was therefore a significant mean reduction in the time taken to complete the task using electronic prescribing of 62 seconds (P=0.01). There were fewer illegible entries or drug errors using electronic prescribing compared to paper prescribing (2.7% vs 5.3%, P=0.68). CONCLUSIONS: Electronic prescribing appears to reduce prescribing errors. However, there is a learning curve for new doctors using electronic prescribing. Training and support is vital during this period in order to reduce prescribing errors. PMID- 26352715 TI - Carlos Finlay: discoverer of the vector of yellow fever. PMID- 26352716 TI - Lower limb lymphoedema and obesity: a much-neglected association. PMID- 26352717 TI - Non-invasive investigation of inverse takotsubo cardiomyopathy in a young woman. PMID- 26352718 TI - Charcot-Marie-Tooth neuropathy and Mobitz II heart block. PMID- 26352719 TI - Visual hallucinations: I can not believe what is happening in front of my eyes. PMID- 26352720 TI - A combination of pulmonary artery aneurysm and deep vein thrombosis. PMID- 26352721 TI - Correspondence. PMID- 26352723 TI - Should all critically ill ventilated patients receive muscle relaxants for intrahospital transfers? PMID- 26352724 TI - Novel psychoactive substances or 'legal highs'. PMID- 26352725 TI - Use and interpretation of cardiac troponin testing. PMID- 26352726 TI - Safety in the acute medical unit: the role of severity of illness, structure of communication and staffing. PMID- 26352727 TI - Hands Tied with Bag Full of Books in Suicidal Hanging. AB - Hanging deaths associated with binding of limbs, masking of a face, and gagging are always suspicious. In suicidal hanging, the victim uses these added techniques to prevent him from backing out of his decision and to ensure death. However, binding of limbs and adding extra weight to the suspension in hanging are not reported. Herein, we report a case where the victim tied a bag containing books weighing 7 kg (15.4 lbs) to both his hands during hanging. The forensic specialist must be aware of the unusual presentation of suicidal hanging which may suggest foul play. The manner of death must be established after detailed analysis of circumstantial evidence, information obtained from the witnesses, complete autopsy, and toxicological examination. PMID- 26352728 TI - Human Chorionic Gonadotropin Stimulation Test in Prepubertal Children with Micropenis Can Accurately Predict Leydig Cell Function in Pubertal or Postpubertal Adolescents. AB - BACKGROUND/AIM: To evaluate the accuracy of the human chorionic gonadotropin (hCG) stimulation test in children with micropenis in predicting later Leydig cell function. METHODS: We conducted a retrospective investigation of testosterone response to a 3-day hCG test (3,000 IU/m2/day) in prepuberty to indicate the need for hormone replacement therapy (HRT) in adolescence. RESULTS: Fifty Japanese boys (range, 0.8-15.4 years of age; median, 8.9) with micropenis were enrolled. Thirty-four spontaneously developed puberty and preserved the ability of testosterone production (group 1), while 16 did not develop any pubertal signs without HRT (group 2). Serum testosterone levels after the hCG test (post-hCG T) in group 2 (range, <0.05-1.1 ng/ml; median, 0.24) were significantly lower than in group 1 (range, 0.5-8.7 ng/ml; median, 2.4; p < 0.0001). Based on true positives who required continuous HRT, the area under the receiver-operating characteristics curve for post-hCG T was 0.983 [95% confidence interval (CI), 0.90-1.00]. The post-hCG T cut-off level corresponding to the Youden index was 1.1 ng/ml (95% CI, 1.0-1.1), with a sensitivity of 100.0% (95% CI, 79.4-100.0) and a specificity of 94.1% (95% CI, 80.3-99.3). CONCLUSIONS: The hCG test in prepubertal children with micropenis can be useful for predicting Leydig cell function in pubertal or postpubertal adolescents. The post-hCG T cut off level of 1.1 ng/ml is recommended to screen for those who will likely require HRT for pubertal development. PMID- 26352729 TI - IL-17A-producing T cells and associated cytokines are involved in the progression of gastric cancer. AB - Interleukin-17A-producing T cells (IL-17A+ T) (IL-17A+CD4+ Th17, IL-17A+CD8+ Tc17 and IL-17A+ gammadeltaT17 cells) and associated cytokines (IL-17A, IL-23 and IL 1beta) play crucial roles in inflammation-associated diseases, such as infection, autoimmunity and tumors. Th17 cells promote human gastric cancer (GC), although the source of intracellular IL-17A and the roles of Tc17 and gammadeltaT17 cells remain poorly understood. In this study, the frequencies of circulating Th17 and gammadeltaT17 cells in patients with GC were found to be significantly increased compared to those in healthy donors; however, Tc17 cells were decreased in these patients, and a negative relationship was found between the frequencies of Th17 and Tc17 cells. Moreover, the cytokine IL-17A was found to be produced mainly by Th17 cells in human peripheral blood. Similarly, serum cytokine levels and relative mRNA expression levels of IL-17A, IL-23 and IL-1beta were significantly increased in patients with GC, and the frequency of Th17 cells was closely associated with serum IL-17A concentrations in patients with GC. Additionally, Th17 cells and associated cytokines were present at significantly different levels during the progression and metastasis of GC, as were Tc17 and gammadeltaT17 cells. Taken together, these findings suggest that IL-17A+ T cells and associated cytokines might play crucial roles in human GC progression and metastasis and thus represent potential targets for treatment. PMID- 26352731 TI - Comparing and contrasting clinical and serological features of juvenile and adult onset myositis: implications for pathogenesis and outcomes. AB - PURPOSE OF REVIEW: To explore the different characteristics of the serological phenotypes identified in juvenile and adult myositis, consider how differences between the two groups might be explained and discuss how this enhances our understanding of disease pathogenesis. RECENT FINDINGS: Current research has focussed on two main areas: first, defining the autoantibody associated disease phenotype in greater detail, particularly with regard to cutaneous disease and within specified populations such as juvenile-onset disease and different ethnic groups, and second, we have gained new insights into disease pathogenesis through studies analysing genetic associations and autoantigen expression. SUMMARY: Although there are many clinically important differences between adult and juvenile-onset myositis, recent work has highlighted many of the similarities at least within autoantibody-defined subgroups. Viewing age at disease onset as a continuum with its own influence on disease phenotype strengthens the ability of autoantibodies to define homogenous disease groups, and may be important in understanding the relationship between autoantibodies and disease pathogenesis. PMID- 26352730 TI - Dual functionality of phosphonic-acid-appended phthalocyanines: inhibitors of urokinase plasminogen activator and anticancer photodynamic agents. AB - Phthalocyanines (Pcs) bearing phosphonic acid groups at the periphery exhibit a potential photodynamic effect to induce phototoxicity on human bladder cancer epithelial cells (UM-UC-3). In vitro photophysical and biological studies show high intrinsic ability to inhibit the activity of urokinase plasminogen activator (uPA) and matrix metalloproteinase-9 (MMP-9). PMID- 26352732 TI - Scleroderma renal crisis. AB - PURPOSE OF REVIEW: There are important knowledge gaps concerning scleroderma renal crisis (SRC), in large part because its rarity has hampered research. Many studies to date share limitations, in particular small samples, prevalent cases, and retrospective study designs. This review features some of the most recent studies that attempt to shed new insights into SRC while trying to overcome those limitations. RECENT FINDINGS: The most important recent progress in the understanding of the pathophysiology of SRC includes identification of novel genetic and serological biomarkers. Outcomes of SRC remain poor and there are also ongoing efforts to identify novel therapeutic strategies, in particular targeting the endothelin-1 pathway. SUMMARY: Meaningful improvement in outcomes of SRC will be predicated on greater understanding of the underlying mechanisms of disease and identification of novel therapeutic and preventive strategies. Some efforts are ongoing but ultimately, international cooperation will be necessary to achieve this for a rare complication of a rare disease. PMID- 26352733 TI - Calcinosis: pathophysiology and management. AB - PURPOSE OF REVIEW: This article reviews the most updated literature regarding the epidemiology, pathophysiology, diagnosis, and treatment of calcinosis cutis in patients with systemic sclerosis (SSc). RECENT FINDINGS: Our review identified observational studies that describe the frequency of calcinosis in SSc and associated clinical features, genetic studies in animal models of heritable disorders leading to calcium deposition, and case series and case reports describing new diagnostic approaches and therapeutic interventions. SUMMARY: Calcinosis cutis is the deposition of calcium in the skin and subcutaneous tissues. It affects almost one quarter of patients with SSc, and is associated with longer disease duration, digital ulcers, acroosteolysis, positive anticentromere antibody, and positive anti-PM/Scl antibody. Local trauma, chronic inflammation, and vascular hypoxia have been proposed as potential pathomechanisms. The development of mouse models that mimic heritable ectopic mineralization disorders are contributing to the understanding of the process of calcification. Diagnosis can be made clinically or with plain radiography. Experimental diagnostic studies include ultrasonography, multidetector computed tomography, and dual-energy computed tomography. Several pharmacologic therapies have been tried for calcinosis with variable results, but surgical excision of calcium deposits remains the mainstay of treatment. PMID- 26352734 TI - Update on macrophages and innate immunity in scleroderma. AB - PURPOSE OF REVIEW: In this review of the literature from 2014 through mid-2015, we examine new data that shed light on how macrophages and other innate immune cells and signals contribute to inflammation, vascular dysfunction, and fibrosis in scleroderma. RECENT FINDINGS: Recent human studies have focused on changes early in scleroderma, and linked macrophages to inflammation in skin and progression of lung disease. Plasmacytoid dendritic cells have been implicated in vascular dysfunction. In mice, several factors have been identified that influence macrophage activation and experimental fibrosis. However, emerging data also suggest that myeloid cells can have differential effects in fibrosis. Sustained signaling through different toll-like receptors can lead to inflammation or fibrosis, and these signals can influence both immune and nonimmune cells. SUMMARY: There are many types of innate immune cells that can potentially contribute to scleroderma and will be worth exploring in detail. Experimentally dissecting the roles of macrophages based on ontogeny and activation state, and the innate signaling pathways in the tissue microenvironment, may also lead to better understanding of scleroderma pathogenesis. PMID- 26352736 TI - Cancer and scleroderma: a paraneoplastic disease with implications for malignancy screening. AB - PURPOSE OF REVIEW: Recent data suggest a paraneoplastic mechanism of scleroderma pathogenesis in unique subsets of scleroderma patients. In this article, we review these data, explore potential links between cancer and scleroderma, and propose an approach to malignancy screening in scleroderma. RECENT FINDINGS: Emerging data have demonstrated that patients with scleroderma and RNA polymerase III autoantibodies have a significantly increased risk of cancer within a few years of scleroderma onset. Genetic alterations in the gene encoding RNA polymerase III (POLR3A) have been identified, and patients with somatic mutations in POLR3A have evidence of mutation specific T-cell immune responses with generation of cross-reactive RNA polymerase III autoantibodies. These data strongly suggest that scleroderma is a by-product of antitumor immune responses in some patients. Additional epidemiologic data demonstrate that patients developing scleroderma at older ages may also have a short cancer-scleroderma interval, suggestive of paraneoplastic disease. SUMMARY: Scleroderma may be a paraneoplastic disease in unique patient subsets. Aggressive malignancy screening in these patients may aid in early cancer detection. Further study is required to determine whether cancer therapy could improve scleroderma outcomes in this patient population. PMID- 26352737 TI - Exploring new mechanisms of weakness-induction, further dissection of clinical phenotypes and identification of new biomarkers in the idiopathic inflammatory myopathies. PMID- 26352735 TI - Origin of fibrosing cells in systemic sclerosis. AB - PURPOSE OF REVIEW: Systemic sclerosis, an autoimmune disease of unknown origin, is characterized by progressive fibrosis that can affect all organs of the body. To date, there are no effective therapies for the disease. This paucity of treatment options is primarily because of limited understanding of the processes that initiate and promote fibrosis in general and a lack of animal models that specifically emulate the chronic nature of systemic sclerosis. Most models capitulate acute injury-induced fibrosis in specific organs. Yet, regardless of the model a major outstanding question in the field is the cellular origin of fibrosing cells. RECENT FINDINGS: A multitude of origins have been proposed in a variety of tissues, including resident tissue stroma, fibrocytes, pericytes, adipocytes, epithelial cells and endothelial cells. Developmentally derived fibroblast lineages have recently been elucidated with fibrosing potential in injury models. Increasing data support the pericyte as a fibrosing cell origin in diverse fibrosis models and adipocytes have recently been proposed. Fibrocytes, epithelial cells and endothelial cells also have been examined, although data do not as strongly support these possible origins. SUMMARY: In this review, we discuss recent evidence arguing in favor of and against proposed origins of fibrosing cells in diverse models of fibrosis. We highlight outstanding controversies and propose how future research may elucidate how fibrosing cells arise and what processes can be targeted in order to treat systemic sclerosis. PMID- 26352739 TI - Ultra fast magic angle spinning solid - state NMR spectroscopy of intact bone. AB - Ultra fast magic angle spinning (MAS) has been a potent method to significantly average out homogeneous/inhomogeneous line broadening in solid-state nuclear magnetic resonance (ssNMR) spectroscopy. It has given a new direction to ssNMR spectroscopy with its different applications. We present here the first and foremost application of ultra fast MAS (~60 kHz) for ssNMR spectroscopy of intact bone. This methodology helps to comprehend and elucidate the organic content in the intact bone matrix with resolution and sensitivity enhancement. At this MAS speed, amino protons from organic part of intact bone start to appear in (1) H NMR spectra. The experimental protocol of ultra-high speed MAS for intact bone has been entailed with an additional insight achieved at 60 kHz. PMID- 26352738 TI - Inhibition of LtxA toxicity by blocking cholesterol binding with peptides. AB - The leukotoxin (LtxA) produced by Aggregatibacter actinomycetemcomitans kills host immune cells, allowing the bacterium to establish an ecological niche in the upper aerodigestive tract of its human host. The interaction of LtxA with human immune cells is both complex and multifaceted, involving membrane lipids as well as cell-surface proteins. In the initial encounter with the host cell, LtxA associates with lymphocyte function-associated antigen-1, a cell surface adhesion glycoprotein. However, we have also demonstrated that the toxin associates strongly with the plasma membrane lipids, specifically cholesterol. This association with cholesterol is regulated by a cholesterol recognition amino acid consensus (CRAC) motif, with a sequence of (334) LEEYSKR(340), in the N-terminal region of the toxin. Here, we have demonstrated that removal of cholesterol from the plasma membrane or mutation of the LtxA CRAC motif inhibits the activity of the toxin in THP-1 cells. To inhibit LtxA activity, we designed a short peptide corresponding to the CRAC(336) motif of LtxA (CRAC(336WT)). This peptide binds to cholesterol and thereby inhibits the toxicity of LtxA in THP-1 cells. Previously, we showed that this peptide inhibits LtxA toxicity against Jn.9 (Jurkat) cells, indicating that peptides derived from the cholesterol-binding site of LtxA may have a potential clinical applicability in controlling infections of repeats-in toxin-producing organisms. PMID- 26352741 TI - Prevalence of Poor Bone Quality in Women Undergoing Spinal Fusion Using Biomechanical-CT Analysis. AB - STUDY DESIGN: Retrospective, cross-sectional analysis of vertebral bone quality in spine-fusion patients at a single medical center. OBJECTIVE: To characterize the prevalence of osteoporosis and fragile bone strength in a spine-fusion population of women with an age range of 50 years to 70 years. Fragile bone strength is defined as the level of vertebral strength below which a patient is at as high a risk of future vertebral fracture as a patient having bone density defined osteoporosis. SUMMARY OF BACKGROUND DATA: Poor bone quality--defined here as the presence of either osteoporosis or fragile bone strength--is a risk factor for spine-fusion patients that often goes undetected but can now be assessed preoperatively by additional postprocessing of computed tomography (CT) scans originally ordered for perioperative clinical assessment. METHODS: Utilizing such perioperative CT scans for a cohort of 98 women (age range: 51-70 yr) about to undergo spine fusion, we retrospectively used a phantomless calibration technique and biomechanical-CT postprocessing analysis to measure vertebral trabecular bone mineral density (BMD) (in mg/cm3) and by nonlinear finite element analysis, vertebral compressive strength (in Newtons, N) in the L1 or L2 vertebra. Preestablished validated threshold values were used to define the presence of osteoporosis (trabecular BMD of 80 mg/cm3 or lower) and fragile bone strength (vertebral strength of 4500 N or lower). RESULTS: Fourteen percent of the women tested positive for osteoporosis, 27% tested positive for fragile bone strength, and 29% were classified as having poor bone quality (either osteoporosis or fragile bone strength). Over this narrow age range, neither BMD nor vertebral strength were significantly correlated with age, weight, height, or body mass index (P values 0.14-0.97 for BMD; 0.13-0.51 for strength). CONCLUSION: Poor bone quality appears to be common in women between ages 50 years and 70 years undergoing spinal fusion surgery. LEVEL OF EVIDENCE: 3. PMID- 26352740 TI - Serum MicroRNAs as Potential Biomarkers for Early Diagnosis of Hepatitis C Virus Related Hepatocellular Carcinoma in Egyptian Patients. AB - Circulating microRNAs are deregulated in liver fibrosis and hepatocellular carcinoma (HCC) and are candidate biomarkers. This study investigated the potential of serum microRNAs; miR-19a, miR-296, miR-130a, miR-195, miR-192, miR 34a, and miR-146a as early diagnostic biomarkers for hepatitis C virus (HCV) related HCC. As how these microRNAs change during liver fibrosis progression is not clear, we explored their serum levels during fibrosis progression in HCV associated chronic liver disease (CLD) and if they could serve as non-invasive biomarkers for fibrosis progression to HCC. 112 Egyptian HCV-HCC patients, 125 non-malignant HCV-CLD patients, and 42 healthy controls were included. CLD patients were subdivided according to Metavir fibrosis-scoring. Serum microRNAs were measured by qRT-PCR custom array. Serum microRNAs were deregulated in HCC versus controls, and except miR-130a, they were differentially expressed between HCC and CLD or late fibrosis (F3-F4) subgroup. Serum microRNAs were not significantly different between individual fibrosis-stages or between F1-F2 (early/moderate fibrosis) and F3-F4. Only miR-19a was significantly downregulated from liver fibrosis (F1-F3) to cirrhosis (F4) to HCC. Individual microRNAs discriminated HCC from controls, and except miR-130a, they distinguished HCC from CLD or F3-F4 patients by receiver-operating-characteristic analysis. Multivariate logistic analysis revealed a panel of four microRNAs (miR-19a, miR-195, miR-192, and miR-146a) with high diagnostic accuracy for HCC (AUC = 0.946). The microRNA panel also discriminated HCC from controls (AUC = 0.949), CLD (AUC = 0.945), and F3-F4 (AUC = 0.955). Studied microRNAs were positively correlated in HCC group. miR-19a and miR-34a were correlated with portal vein thrombosis and HCC staging scores, respectively. In conclusion, studied microRNAs, but not miR-130a, could serve as potential early biomarkers for HCC in high-risk groups, with miR-19a as a biomarker for liver fibrosis progression to cirrhosis to HCC. We identified a panel of four serum microRNAs with high accuracy in HCC diagnosis. Additional studies are required to confirm this panel and test its prognostic significance. PMID- 26352742 TI - Rigid Instrumentation for Neuromuscular Scoliosis Improves Deformity Correction Without Increasing Complications. AB - STUDY DESIGN: Retrospective chart and radiographic review. OBJECTIVE: To evaluate spinopelvic fixation technical advancements for the treatment of neuromuscular scoliosis. SUMMARY OF BACKGROUND DATA: Implants for vertebral and pelvic fixation have evolved without data demonstrating the benefit for neuromuscular scoliosis. The aim of this study was to evaluate this evolution in terms of deformity correction, complications, and implant cost. METHODS: Patients treated with posterior spinal fusion to the pelvis for neuromuscular scoliosis with minimum 1 year follow-up from 1998 to 2012 were reviewed. Constructs were defined as nonrigid (>50% sublaminar wire fixation with Galveston or iliac screw pelvic fixation) and rigid (>=50% pedicle screw fixation with iliac or sacral alar iliac screw pelvic fixation). RESULTS: Eighty patients were identified: cerebral palsy (55%), myelomeningocele (16%), syndrome (8%), muscular dystrophy (15%), or other neuromuscular disorders (6%). A total of 95% were nonambulatory. Mean follow-up was 3.9 years (range 1-12 years). Construct types were 23 nonrigid and 57 rigid. Estimated construct cost was greater in the rigid group at $15,488 as compared with $3128 in the nonrigid group despite the lower anchor density in the rigid construct group (1.38 vs. 1.80, P < 0.001). Open anterior releases were more frequently performed in the nonrigid group (13/23 vs. 5/57, P < 0.001). Deformity correction at final follow-up was significantly greater for both Cobb angle and pelvic obliquity in the rigid group. The rates of wound infection, wound dehiscence, implant prominence, and mechanical failure of the fixation were not significantly different. The pseudarthrosis rate requiring revision surgery was 22% in nonrigid group and 5% in the rigid group (P = 0.026). CONCLUSION: Advances in spinopelvic fixation have resulted in improved deformity correction with lower rates of pseudarthrosis and a decreased need for anterior release. This study demonstrates the benefits of modern spinopelvic fixation techniques. PMID- 26352743 TI - Characteristics of Trauma Patients With Potential Cervical Spine Injuries Underimmobilized by Prehospital Providers. AB - STUDY DESIGN: This study was a retrospective chart review to determine characteristics of patients under-immobilized by prehospital providers. OBJECTIVE: Our goal was to examine the characteristics of patients who met the criteria for spinal immobilization but were inappropriately cleared. SUMMARY OF BACKGROUND DATA: Many emergency medical services (EMS) use selective spinal immobilization (SSI) based on the NEXUS criteria. However, there is been research examining patients who are under-immobilized by EMS. METHODS: This was a retrospective chart review over 18 months of a single EMS service. We reviewed all charts dispatched as "motor vehicle crash" (MVC) or "fall". We then determined, whether the patient met the criteria for SSI under Pennsylvania protocols, which mirror the NEXUS criteria. RESULTS: Our EMS system responded to 1151 falls and MVCs over the study period. Seventy-six patients were immobilized leaving 1075 patients who had clinical clearance of their cervical spine. Of these patients, 4/1075 (0.3%) were considered to be under-immobilized. All 4 of these patients had intoxication or altered mentation mentioned in their charts. Two of these patients had CT scans of their cervical spine, with both being negative. One patient eloped from the ED before any imaging, and 1 patient was clinically cleared. CONCLUSION: EMTs are very proficient in following the SSI guidelines with an under-immobilization rate of approximately 0.3% in our study. However, all patients who were under-immobilized were under the influence of alcohol. There were no patients who were not immobilized and had cervical spine injuries. This was a limited chart review involving only 2 dispatch categories. EMTs should be cautious while evaluating patients with possible spinal injuries who are under the influence of alcohol. LEVEL OF EVIDENCE: 4. PMID- 26352744 TI - Surgical Incision and Approach in Thoracolumbar Extreme Lateral Interbody Fusion Surgery: An Anatomic Study of the Diaphragmatic Attachments. AB - STUDY DESIGN: Cadaveric study. OBJECTIVE: To provide anatomical basis for deciding the surgical approach and skin incision in thoracolumbar extreme lateral interbody fusion (XLIF) by delineating the attachment points of diaphragm. SUMMARY OF BACKGROUND DATA: Although the general anatomy of the thoracic diaphragm is well described, the specific attachment points of diaphragm concerned with the XLIF approach is yet to be elaborated. METHODS: Dissections were performed on 21 cases of formalin fixed specimens (12 males, 9 females, a total of 42 sets of data). Special attention was paid to the attachment points of diaphragm on both sides at the midaxillary line (MAL point) and the vertebral level parallel to the MAL point (VL-MAL). The attachment points of diaphragm on the front and back edge of the spinal column (FES point and BES point) were also described. RESULTS: The MAL point of diaphragm muscle lied between the inferior edge of the 10th rib and the superior edge of the 12th rib (20 out of 21 on left, 21 out of 21 on right). VL-MAL lied between L1 and L2 vertebrae level (20 out of 21 on left, 18 out of 21 on right). The attachments on both sides of the vertebral column mainly located between the upper edge of T12 vertebrae and L1-L2 disc (38 out of 42). CONCLUSION: A transthoracic approach should be considered when the target level was above T12 vertebrae, whereas a retroperitoneal approach should be chosen when target level was below L1-L2 disc. If the target level is located between T12 and L1-L2 disc, whether via transthoracic, retropleural, or retroperitoneal approach should be determined according to the conditions of patients and the skill and experience of the surgeon. Incision should be made above the 10th rib for the transthoracic approach and below the 12th rib for the retroperitoneal approach. LEVEL OF EVIDENCE: 4. PMID- 26352745 TI - Utility of Readmission Rates as a Quality of Care Measure and Predictors of Readmission Within 30 Days After Spinal Surgery: a Single-Center, Multivariate Analysis. AB - STUDY DESIGN: A retrospective review. OBJECTIVE: The aim of this study was to establish clinically relevant readmission rates that permit accurate comparisons, improve risk-stratification, and direct efforts to minimize readmissions. SUMMARY OF BACKGROUND DATA: The 30-day hospital readmission rate is a quality of care measure that is now being used to compare hospitals in a publicly available manner. METHODS: Records from 1187 consecutive spinal surgeries at Northwestern Memorial Hospital in 2010 were retrospectively reviewed and data were collected that described the patient, surgical procedure, hospital course, complications, and readmissions. The primary outcome of interest was readmission to the hospital within 30 days. Potential risk factors were examined for association with the outcome first via bivariate analysis, with significant predictors further examined by a multivariable model. Identified readmissions were independently reviewed by attending spinal neurosurgeons not involved with the cases to determine whether the readmissions were procedure related or procedure unrelated with respect to accepted criteria. RESULTS: The overall readmission rate was 6.1%. Of these readmissions, 37.5% were deemed procedure related upon attending review, leading to a procedure-related readmission rate of 2.3%. Upon multivariate analysis, only 3 variables were found to be significant predictors of readmission: 2 or more patient comorbidities [odds ratio (OR) 3.72, 95% confidence interval (95% CI) 1.62-8.56], an admission to the ICU (OR 2.68, 95% CI 1.45-4.95), and each additional spinal level involved (OR 1.11, 95% CI 1.02 1.21). CONCLUSIONS: Our study suggests that predictors for all-cause 30-day readmission following spinal procedures include number of spinal levels performed during the surgery, number of patient comorbidities present at the time of surgery, and whether the admission required an ICU stay. Future work should focus on developing best practices to modify medical risk factors and comorbidities that have the potential to decrease 30-day readmission rates. LEVEL OF EVIDENCE: 3. PMID- 26352746 TI - Posterior Arch Defect of the Atlas Associated to Absence of Costal Element of Foramen Transversarium from 16th-Century Sardinia (Italy). AB - STUDY DESIGN: A paleopathological case of posterior arch defect of the atlas associated to the absence of costal element of the foramen transversarium. OBJECTIVE: In living patients as well as in postmortem analysis it should be difficult to distinguish between a congenital and an acquired anomaly. Any anomaly in the anatomy of atlas should be taken into consideration by clinicians, surgeons, radiologists, and anatomists in order to avoid misinterpretations and clinical complications. SUMMARY OF BACKGROUND DATA: Posterior arch defect has a current occurrence of approximately 4%. Posterior arch schisis is attributed to the defective or absent development of the cartilaginous preformation of the arch rather than a disturbance of the ossification. The absence of costal element of the foramen transversarium has an incidence of ranging from 2% to 10% and is attributed to a developmental defect or to variations in the course of the vertebral artery. METHODS: The skeleton of a man aged 20-30 years, brought to light in the plague cemetery of 16th century Alghero (Sardinia), showed anomalies of the atlas, consisting in failure of the midline fusion of the 2 hemiarches with a small gap and an open anterior foramen trasversarium on the left side. A macroscopic, radiological, and stereomicroscopic study was carried out. RESULTS: The study allowed to rule out a traumatic origin of the defects and to diagnose an association of 2 congenital anomalies. CONCLUSION: Osteoarchaeological cases provides with a valuable opportunity to examine and describe variations in the anatomy of the atlas. LEVEL OF EVIDENCE: N/A. PMID- 26352747 TI - Is There an Association Between Radiological Severity of Lumbar Spinal Stenosis and Disability, Pain, or Surgical Outcome?: A Multicenter Observational Study. AB - STUDY DESIGN: Observational multicenter study. OBJECTIVE: To evaluate if the severity of lumbar spinal stenosis (LSS) on magnetic resonance imaging (MRI) correlates with preoperative disability, pain, or surgical outcomes. SUMMARY OF BACKGROUND DATA: Surgeons use the morphological appearance of LSS on MRI for clinical decision making. However, the associations between radiological severity of LSS and disability, pain, or surgical outcomes remain unclear. METHODS: Evaluation of severity of LSS on preoperative MRI according to the Schizas morphological classification. Patient and treatment data were retrieved from the Norwegian Registry for Spine Surgery. Preopertaive outcome measures were Oswestry disability index (ODI) and numeric rating scale (NRS) scores for back and leg pain. Postopertive outcome measures were ODI and NRS scores for back and leg pain at 1 year, changes in ODI and NRS scores after treatment, duration of surgery, length of hospital stay, and perioperative complications. RESULTS: Of 202 patients included, 7 were found to have mild stenosis, 38 had moderate stenosis, 108 had severe stenosis, and 49 had extreme stenosis. The radiological severity of LSS was not linked to preoperative ODI (P = 0.089), NRS back pain (P = 0.273), or NRS leg pain (P = 0.282) scores. There were no differences in ODI (P = 0.933), NRS back pain (P = 0.652), or NRS leg pain (P = 0.912) scores after 1 year. The radiological severity of stenosis was not associated with change in ODI (P = 0.494), NRS back pain (P = 0.235), NRS leg pain (P = 0.790), duration of surgery (P = 0.661), length of hospital stay (P = 0.739), or perioperative complication rates (P = 0.467). CONCLUSION: Among patients who underwent decompressive surgery for LSS, radiological severity of stenosis was not associated with preoperative disability and pain, or clinical outcomes 1 year after surgery. In this patient group, the radiological severity of LSS has no clear clinical correlation and should therefore not be overemphasized in clinical decision making. LEVEL OF EVIDENCE: 2. PMID- 26352748 TI - Failed Cartilaginous Grafts in the Eyelid: A Retrospective Clinicopathological Analysis of 5 Cases. AB - PURPOSE: To analyze the clinical and histopathologic features of 5 failed autologous cartilaginous grafts to the lower eyelids and to analyze the reasons for these failures. METHODS: In this retrospective case series, the data collected included patient ages, reasons for and duration of cartilaginous graft implants, sources of cartilaginous grafts, and clinical and histopathologic findings at time of graft removal using hematoxylin and eosin, elastic, Alcian blue, and Masson trichrome staining for analysis of tissue alterations. RESULTS: Five cartilaginous, posterior lamellar lower eyelid grafts were complicated by eyelid thickening or retraction, graft extrusion, and entropion. Histopathologic findings included segmentation of the original single implant, stripped of its perichondrium, due to "kerfing," sometimes with overlapping of the segments and scar formation between the segments. In place of the perichondrium that had been removed during the preparation the graft implants, a fibrous pseudoperichondrial capsule had formed. Pyknotic nuclei in varying degrees were typically found in the center of the grafts, despite a high degree of preservation of the extracellular matrix (collagenous, elastic, and proteoglycan components). No evidence of inflammation, cartilaginous vascularization, or necrosis was identified in any graft. CONCLUSION: Despite minimal reactive processes, kerfing (partial thickness cuts made in the graft to increase its pliancy) may be partially responsible for graft migration, deformation, and surgical failure. The consequences were graft fragmentation and overlapping of the multiple fragments. Graft migration can be exacerbated if a posterior lamellar graft is used to correct an anterior lamellar deficiency. Interference with the overall architectural integrity of the graft and its extracellular matrix appears to play no role in failure, despite removal of the perichondrium. Mild to moderate degrees of chondrocytic dropout in the absence of necrosis and inflammation are probably attributable to the thick and coarsely textured collagen of the fibrous pseudoperichondrial capsule that may impede diffusion of nutrients into the center of the graft. PMID- 26352749 TI - Increased Signal Intensity in the Dentate Nucleus on Unenhanced T1-Weighted Images After Gadobenate Dimeglumine Administration. AB - OBJECTIVES: The aim of this study was to compare changes in signal intensity (SI) ratios of the dentate nucleus (DN) to pons and cerebrospinal fluid (CSF) on unenhanced T1-weighted magnetic resonance imaging (MRI) scans between the first and last MRI using the linear gadolinium-based contrast agent gadobenate dimeglumine. MATERIALS AND METHODS: The study was approved by the ethical committee of the University of Heidelberg (S-324/2014), and written informed consent was waived due to the retrospective character of the study. Fifty patients who underwent at least 5 consecutive MRI examinations (plus an additional last MRI for reference) with the exclusive use of gadobenate dimeglumine were analyzed retrospectively. The difference of DN-to-pons and DN-to CSF mean SI ratios was calculated on unenhanced T1-weighted images between the first and last examination. Results were compared with previously published data on gadopentetate dimeglumine and gadoterate meglumine. RESULTS: Signal intensity ratio differences for DN-to-pons and DN-to-CSF were significantly greater than 0 (pons: 0.0399 +/- 0.0307, P < 0.001; CSF: 0.1439 +/- 0.1524, P < 0.001). No control variable consistently predicted the SI ratio difference for the DN-to pons and the DN-to-CSF ratio. Compared with previously published data, the difference in SI increase between gadopentetate dimeglumine and gadobenate dimeglumine was not significant for the DN-to-pons ratio (P = 0.906). In contrast, the DN-to-CSF ratio difference was significantly lower (P < 0.001) for gadobenate dimeglumine. Dentate nucleus-to-pons (P < 0.001) and DN-to-CSF (P = 0.017) ratio differences were both significantly higher for gadobenate dimeglumine than for gadoterate meglumine. CONCLUSIONS: The present study found an increase in SI in the DN after serial injections of gadobenate dimeglumine. Further studies are needed to clarify the potential of different linear gadolinium-based contrast agents to cause SI increase in the DN. PMID- 26352750 TI - Can Ferumoxytol be Used as a Contrast Agent to Differentiate Between Acute and Chronic Inflammatory Kidney Disease?: Feasibility Study in a Rat Model. AB - OBJECTIVES: Ferumoxytol, an intravenous iron supplement, can be used in off-label mode as a contrast agent in magnetic resonance imaging. The aim of this study was to assess whether ferumoxytol can be used as a marker of inflammation in animal models of acute and chronic inflammatory kidney diseases. MATERIAL AND METHODS: The institutional animal care committee approved this study. A total of 18 rats were examined: 6 healthy Sprague Dawley rats as a control group; 6 rats with polycystic kidney disease (PKD) as a model for chronic inflammatory disease; Thy 1, an antibody triggering glomerulonephritis, was injected in 6 rats as a model for acute inflammation. Each rat was examined directly before and 24 hours after intravenous administration of ferumoxytol at a dose of 30 mg Fe/kg body weight. T2* times of renal tissue were approximated using a multiecho sequence. Changes in relative T2* times and T2 signal intensity after ferumoxytol injection were calculated. RESULTS: Statistically significant differences between the 3 groups were found: the T2* times of both, Thy-1 and PKD rats were statistically significant different compared with the control group (T2* time ratio after/before: Thy-1, 0.21; PKD, 0.19, control, 0.28; P = 0.002). The highest T2 signal loss in the renal cortex was observed in the Thy-1 rats (T2 signal intensity ratio after/before: Thy-1, 0.49; PKD, 0.79; control, 0.78; P = 0.0005). CONCLUSIONS: Ferumoxytol-enhanced magnetic resonance imaging allows detection and differentiation of acute and chronic inflammatory kidney disease based on different patterns of parenchymal ferumoxytol depositions. Ferumoxytol thus might help to differentiate between different types of inflammation in various kidney diseases. PMID- 26352751 TI - Temperature-Mediated Kill and Oviposition of Western Cherry Fruit Fly (Diptera: Tephritidae) in the Presence of Spinosad. AB - Western cherry fruit fly, Rhagoletis indifferens Curran (Diptera: Tephritidae), is a quarantine pest of sweet cherry (Prunus avium (L.) L.) that is managed using insecticides, including spinosad, an organic compound that can be applied in low spray volumes. Identifying factors that can increase the efficacy of spinosad can be useful for improving fly control. Here, the major objective was to determine if temperature mediates kill and oviposition of R. indifferens in the presence of low spinosad coverage in the laboratory. Experiments were conducted by placing flies in cages with cherries and with a Petri dish containing 3-12 small spots of dry spinosad at 18.3, 23.9, and 29.4 degrees C. Effects of spinosad rates were also determined. More flies were killed at 23.9 and 29.4 degrees C than at 18.3 degrees C by 1-7 d post exposure. More flies were killed at 29.4 than 23.9 degrees C by 1 d post exposure. However, flies laid more eggs at these temperatures than at 18.3 degrees C. Higher spinosad rates increased kill and decreased oviposition, but even within the highest rate, oviposition was greater at 29.4 than 18.3 degrees C. More flies walked over 5-min observation periods at 29.4 and 23.9 degrees C than 18.3 degrees C, suggesting higher temperatures up to 29.4 degrees C increase kill by increasing fly contact with spinosad as well as increase oviposition rate. Results suggest that spinosad rates in sprays used against R. indifferens should be greater at higher than lower ambient temperatures. PMID- 26352752 TI - Vineyard Colonization by Hyalesthes obsoletus (Hemiptera: Cixiidae) Induced by Stinging Nettle Cut Along Surrounding Ditches. AB - Stinging nettle (Urtica dioica L.) is the most important host plant for both phytoplasma associated with Bois noir disease of the grapevine and its vector Hyalesthes obsoletus Signoret (Hemiptera: Cixiidae). Vector abundance in vineyards is favored by stinging nettle growing in surrounding areas. Nettle control by herbicides or cutting can reduce vector population in vineyards. However, chemical weeding can cause environmental problems. Many authors suggest that stinging nettle control applied during H. obsoletus flight could force adults to migrate into vineyards. We evaluate if cutting of nettle growing along ditches during adult flight favors vineyard colonization by H. obsoletus. Three different weed management regimes ("no cuts," "one cut" just before the beginning of adult flight, and "frequent cuts" over the whole vegetative season) were applied to the herbaceous vegetation in ditches bordering two vineyards. The flight dynamics of H. obsoletus were recorded by placing yellow sticky traps on the vegetation along the ditches and at different positions in the vineyards. Frequent stinging nettle cuts (compared with a single cut) in surrounding areas favored the dispersion of vectors inside the vineyards. Stinging nettle control should be based on an integration of a single herbicide application before H. obsoletus emergence followed by frequent cuts to minimize negative side effects of chemical weeding. In organic viticulture, a frequent-cuts strategy should avoid cuts during H. obsoletus flight period, at least in the first year of adoption. PMID- 26352753 TI - Spray Toxicity and Risk Potential of 42 Commonly Used Formulations of Row Crop Pesticides to Adult Honey Bees (Hymenoptera: Apidae). AB - To combat an increasing abundance of sucking insect pests, >40 pesticides are currently recommended and frequently used as foliar sprays on row crops, especially cotton. Foraging honey bees may be killed when they are directly exposed to foliar sprays, or they may take contaminated pollen back to hives that maybe toxic to other adult bees and larvae. To assess acute toxicity against the honey bee, we used a modified spray tower to simulate field spray conditions to include direct whole-body exposure, inhalation, and continuing tarsal contact and oral licking after a field spray. A total of 42 formulated pesticides, including one herbicide and one fungicide, were assayed for acute spray toxicity to 4-6-d old workers. Results showed significantly variable toxicities among pesticides, with LC50s ranging from 25 to thousands of mg/liter. Further risk assessment using the field application concentration to LC1 or LC99 ratios revealed the risk potential of the 42 pesticides. Three pesticides killed less than 1% of the worker bees, including the herbicide, a miticide, and a neonicotinoid. Twenty-six insecticides killed more than 99% of the bees, including commonly used organophosphates and neonicotinoids. The remainder of the 13 chemicals killed from 1-99% of the bees at field application rates. This study reveals a realistic acute toxicity of 42 commonly used foliar pesticides. The information is valuable for guiding insecticide selection to minimize direct killing of foraging honey bees, while maintaining effective control of field crop pests. PMID- 26352755 TI - Authentication of Whey Protein Powders by Portable Mid-Infrared Spectrometers Combined with Pattern Recognition Analysis. AB - The objective of this study was to develop a simple and rapid method to differentiate whey protein types (WPC, WPI, and WPH) used for beverage manufacturing by combining the spectral signature collected from portable mid infrared spectrometers and pattern recognition analysis. Whey protein powders from different suppliers are produced using a large number of processing and compositional variables, resulting in variation in composition, concentration, protein structure, and thus functionality. Whey protein powders including whey protein isolates, whey protein concentrates and whey protein hydrolysates were obtained from different suppliers and their spectra collected using portable mid infrared spectrometers (single and triple reflection) by pressing the powder onto an Attenuated Total Reflectance (ATR) diamond crystal with a pressure clamp. Spectra were analyzed by soft independent modeling of class analogy (SIMCA) generating a classification model showing the ability to differentiate whey protein types by forming tight clusters with interclass distance values of >3, considered to be significantly different from each other. The major bands centered at 1640 and 1580 cm(-1) were responsible for separation and were associated with differences in amide I and amide II vibrations of proteins, respectively. Another important band in whey protein clustering was associated with carboxylate vibrations of acidic amino acids (~1570 cm(-1)). The use of a portable mid-IR spectrometer combined with pattern recognition analysis showed potential for discriminating whey protein ingredients that can help to streamline the analytical procedure so that it is more applicable for field-based screening of ingredients. PRACTICAL APPLICATION: A rapid, simple and accurate method was developed to authenticate commercial whey protein products by using portable mid infrared spectrometers combined with chemometrics, which could help ensure the functionality of whey protein ingredients in food applications. PMID- 26352754 TI - Lethal and Sublethal Effects of Insecticides on the Egg Parasitoid Telenomus podisi (Hymenoptera: Platygastridae). AB - Insecticide use remains controversial, and subjected to increasing environmental and health concerns, even when recent insecticide groups are considered. Neonicotinoids and even bioinsecticides are in the forefront of discussions regarding their nontarget safety. The ubiquitous focus on the lethal effects of insecticides on nontarget species has been expanding to sublethal effects, as sublethal exposure extends for a longer time and affects a broader range of (nontarget) species. Here we explored the lethal and sublethal effects of a lambda-cyhalothrin + thiamethoxan mixture, the neonicotinoid imidacloprid, and the bioinsecticide azadirachtin on the egg parasitoid Telenomus podisi Ashmead, an important parasitoid of stink bug Euschistus heros (F.), a key soybean pest in neotropical America. Contact with dry insecticide residue on glass surface and (parasitized and healthy) host egg immersion exposure bioassays were performed, assessing their acute lethal effects, and their potential sublethal impairment of parasitism, adult emergence, and fertility of the egg parasitoid. Both imidacloprid and the insecticide mixture exhibited high acute lethal activity toward the parasitoid under contact with dry insecticide residue. These insecticides compromised parasitism and wasp emergence when exposure took place before parasitism. In contrast, azadirachtin did not affect adult survival. However, this bioinsecticide compromised parasitism and progeny production, impairing the female parasitoid reproductive potential. Our results indicate strong negative effects of imidacloprid, and specially of the mixture lambda cyhalthrin + thiamethoxan. However, even azadirachtin, which exhibited low acute lethality, exhibited significant negative sublethal effects on parasitism and population growth of egg parasitoid, cautioning against their use and the need of semifield and field assessments to confirm such an impact. PMID- 26352756 TI - Naphthylaminoborane: from structural switches to frustrated Lewis pair reactivity. AB - A series of naphthyl-bridged amino-borane derivatives, namely 1-(dimethylamino)-8 naphthylboranes (1, 3, 5, 7) and 5-(dimethylamino)-6-acenaphthylboranes (2, 4, 6, 8, 10, 11), differing in the steric and electronic properties of the boryl moiety, have been synthesized and fully characterized by spectroscopic and crystallographic means. Structural X-ray analysis of the peri-atom displacement and ring torsion angles served to experimentally assess the presence and magnitude of the B-N interactions. The reversible quaternarization of nitrogen has been explored and was found to provide an efficient switch corresponding to different molecular organizations. The electronic characteristics of the nature of B-N interactions were further studied by Natural Bonding Orbital analysis derived from the theoretically calculated electron densities. This real-space bonding indicator discriminates the bonding B-N contact in 5 from the nonbonding in 8, which correlates with the flexibility of the naphthyl scaffold to respond to the Lewis acidity of boron allowing shorter peri interactions. Whereas, the steric shielding imposed by the two mesityl groups, and/or the rigidity of the acenaphthene framework disrupt B-N interaction. Thus, this communication reports on the modulation of the B-N bonding continuum by means of structural tuning leading to a molecular switch, as well as its implications towards revealing FLP reactivities through the isolation of intermediates of a stepwise mechanism. PMID- 26352757 TI - Monitoring Spongospora subterranea Development in Potato Roots Reveals Distinct Infection Patterns and Enables Efficient Assessment of Disease Control Methods. AB - Spongospora subterranea is responsible for significant potato root and tuber disease globally. Study of this obligate (non-culturable) pathogen that infects below-ground plant parts is technically difficult. The capacity to measure the dynamics and patterns of root infections can greatly assist in determining the efficacy of control treatments on disease progression. This study used qPCR and histological analysis in time-course experiments to measure temporal patterns of pathogen multiplication and disease development in potato (and tomato) roots and tubers. Effects of delayed initiation of infection and fungicidal seed tuber and soil treatments were assessed. This study found roots at all plant developmental ages were susceptible to infection but that delaying infection significantly reduced pathogen content and resultant disease at final harvest. The pathogen was first detected in roots 15-20 days after inoculation (DAI) and the presence of zoosporangia noted 15-45 DAI. Following initial infection pathogen content in roots increased at a similar rate regardless of plant age at inoculation. All fungicide treatments (except soil-applied mancozeb which had a variable response) suppressed pathogen multiplication and root and tuber disease. In contrast to delayed inoculation, the fungicide treatments slowed disease progress (rate) rather than delaying onset of infection. Trials under suboptimal temperatures for disease expression provided valuable data on root infection rate, demonstrating the robustness of monitoring root infection. These results provide an early measure of the efficacy of control treatments and indicate two possible patterns of disease suppression by either delayed initiation of infection which then proceeds at a similar rate or diminished epidemic rate. PMID- 26352758 TI - Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry-based metabolic profiling of human serum prior to and following radical resection of colorectal carcinoma. AB - Nearly one quarter of patients with colorectal carcinoma (CRC) were diagnosed at an advanced stage. Under these circumstances, radical resection of the tumor is the best strategy to enhance the five-year survival rate. However, up to 50% of post-operative patients experience cancer recurrence within the first few years. Therefore, post-operative surveillance is important. However, currently performed post-operative monitoring relies on relatively dated methods with insufficient sensitivity and specificity. The present study applied an advanced technology of ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry in order to examine changes in metabolite patterns in serum with the aim of identifying reliable biomarkers in patients with CRC at various time-points. Serum samples were collected from and 20 CRC patients prior to radical resection (group 1) and one month following radical resection (group 2) as well as from 20 healthy volunteers (group 3). Multivariate pattern recognition was used to identify potential biomarkers of CRC. Compared with healthy volunteers, three groups of biomarkers were identified in patients with CRC (P<0.05), namely phosphatidylcholines (PCs), lysophosphatidylcholines (LPCs) and diacylglycerols (DAGs). However, no statistical difference in the levels of these biomarkers between pre-operative and post-operative CRC patients was identified (P>0.05). PCs and LPCs, which contain polyunsaturated fatty acids, were decreased, whereas LPCs and DAGs, which contain saturated fatty acids, were increased in CRC patients. The present study demonstrated that obvious metabolic disturbances occur during the development of CRC and provided a novel analytic method, which is likely to be used as a diagnostic tool for CRC and may help to improve the patients' prognosis. PMID- 26352759 TI - Application of design of experiments (DoE) optimization to the one-pot synthesis of 4,6-dihydropteridinones. AB - A design of experiments (DoE) analysis of a tandem SnAr-amidation cyclization reaction between 4-chloropyrimidin-5-amine and (S)-N-methylalanine to form (S) 7,8-dimethyl-7,8-dihydropteridin-6(5H)-one is reported. Five reaction variables were optimized using DoE and conversion was improved from 26% to 74%, with a significant reduction in reaction time while retaining high optical purity. The optimized conditions were applied to the synthesis of a wide variety of analogs and the expanded reaction substrate scope included a variety of amino acids and pyrimidines. Products were obtained in isolated yields up to 95% and enantiomeric excess as high as 98%. PMID- 26352761 TI - Dissemination of an innovative mastery learning curriculum grounded in implementation science principles: a case study. AB - Dissemination of a medical education innovation, such as mastery learning, from a setting where it has been used successfully to a new and different medical education environment is not easy. This article describes the uneven yet successful dissemination of a simulation-based mastery learning (SBML) curriculum on central venous catheter (CVC) insertion for internal medicine and emergency medicine residents across medical education settings. The dissemination program was grounded in implementation science principles. The article begins by describing implementation science which addresses the mechanisms of medical education and health care delivery. The authors then present a mastery learning case study in two phases: (1) the development, implementation, and evaluation of the SBML CVC curriculum at a tertiary care academic medical center; and (2) the dissemination of the SBML CVC curriculum to an academic community hospital setting. Contextual information about the drivers and barriers that affected the SBML CVC curriculum dissemination is presented. This work demonstrates that dissemination of mastery learning curricula, like all other medical education innovations, will fail without active educational leadership, personal contacts, dedication, hard work, rigorous measurement, and attention to implementation science principles. The article concludes by presenting a set of lessons learned about disseminating an SBML CVC curriculum across different medical education settings. PMID- 26352760 TI - Aberrant differentiation of Tsc2-deficient teratomas associated with activation of the mTORC1-TFE3 pathway. AB - The model animal of renal cell carcinoma (RCC), the Eker rat, has a germline mutation in the tuberous sclerosis 2 (Tsc2) gene. Heterozygous mutants develop RCCs by second hit in the wild-type Tsc2 allele, whereas homozygous mutants are embryonic lethal. In the present study, a new cell differentiation model was developed to study the mechanism of Tsc2 mutation-associated pathogenesis by generating Tsc2-deficient embryonic stem cells (ESCs) from Eker rats. Tsc2+/+, Tsc2+/- and Tsc2-/- ESCs were all capable of generating three germ layers: mesoderm, ectoderm, and endoderm. Interestingly, epithelial tumor-like abnormal ductal structures were reproducibly observed in Tsc2-/- teratomas from different ESC lines. Immunohistochemical analysis revealed that mammalian target of rapamycin complex 1 (mTORC1) signaling was activated in abnormal ducts of Tsc2-/- teratomas, on the basis of positive staining for p-S6 and p-4EBP1. In these abnormal ducts, expression levels of epithelial markers (i.e., megalin and cubilin) and the cytoplasmic localization of E-cadherin and beta-catenin were similar to those in Eker rat RCCs. Moreover, a transcription factor regulated by mTORC1, named TFE3, was located in the nuclei of abnormal ducts and Eker rat RCCs. As a negative regulator of ESC differentiation, TFE3 may result in tissue specific differentiation defects related to tumorigenesis in Eker rats and Tsc2-/ teratomas. The present study suggests that ESCs derived from Eker rats constitute a novel experimental tool with which to analyze differentiation defects and cell-type specific pathogenesis associated with Tsc2 deficiency. PMID- 26352762 TI - Association of Characteristics, Deficits, and Outcomes of Residents Placed on Probation at One Institution, 2002-2012. AB - PURPOSE: To describe the population of residents placed on probation, identify learner characteristics associated with being placed on probation, and describe immediate and long-term career outcomes for those placed on probation as compared with matched controls. METHOD: The authors collected data for residents at the University of Colorado School of Medicine placed on probation from July 2002 to June 2012, including postgraduate year placed on probation, deficits identified, mandated evaluation for physical and mental health, duration of probation, disability accommodations requested, and number of additional training months required. They were retrospectively compared with 102 controls matched for specialty, matriculation, and postgraduate year. Variables assessed included demographics, academic performance, license status, specialty, state board certification, and board citations. RESULTS: Of 3,091 residents, 3.3% were placed on probation (88 residents; 14 fellows). Compared with controls, those on probation were more likely to be international medical graduates, married, not Caucasian, older (all P < .001), male (P = .01), to have transferred from another graduate medical education training program, and to have taken time off between medical school and residency (all P < .001). Among those currently in practice, 53 (63.9%) were board certified compared with 93 (100%) of the controls. Placement on probation was associated with failure to graduate and lack of board certification. All 7 graduates cited by state medical boards were in the probation group. CONCLUSIONS: Further research is needed to understand these associations and to determine whether changes in curricula or remediation programs may alter these outcomes. PMID- 26352763 TI - Taxonomy of Trauma Leadership Skills: A Framework for Leadership Training and Assessment. AB - PURPOSE: Good leadership is essential for optimal trauma team performance, and targeted training of leadership skills is necessary to achieve such leadership proficiency. To address the need for a taxonomy of leadership skills that specifies the skill components to be learned and the behaviors by which they can be assessed across the five phases of trauma care, the authors developed the Taxonomy of Trauma Leadership Skills (TTLS). METHOD: Critical incident interviews were conducted with trauma team leaders and members from different specialties emergency physicians, trauma surgeons, anesthesiologists, and emergency ward nurses-at three teaching hospitals in the Netherlands during January-June 2013. Data were iteratively analyzed for examples of excellent leadership skills at each phase of trauma care. Using the grounded theory approach, elements of excellent leadership skills were identified and classified. Elements and behavioral markers were sorted and categorized using multiple raters. In a two round verification process in late 2013, the taxonomy was reviewed and rated by trauma team leaders and members from the multiple specialties for its coverage of essential items. RESULTS: Data were gathered from 28 interviews and 14 raters. The TTLS details 5 skill categories (information coordination, decision making, action coordination, communication management, and coaching and team development) and 37 skill elements. The skill elements are captured by 67 behavioral markers. The three-level taxonomy is presented according to five phases of trauma care. CONCLUSIONS: The TTLS provides a framework for teaching, learning, and assessing team leadership skills in trauma care and other complex, acute care situations. PMID- 26352764 TI - Wisdom in Medicine: What Helps Physicians After a Medical Error? AB - PURPOSE: Confronting medical error openly is critical to organizational learning, but less is known about what helps individual clinicians learn and adapt positively after making a harmful mistake. Understanding what factors help doctors gain wisdom can inform educational and peer support programs, and may facilitate the development of specific tools to assist doctors after harmful errors occur. METHOD: Using "posttraumatic growth" as a model, the authors conducted semistructured interviews (2009-2011) with 61 physicians who had made a serious medical error. Interviews were recorded, professionally transcribed, and coded by two study team members (kappa 0.8) using principles of grounded theory and NVivo software. Coders also scored interviewees as wisdom exemplars or nonexemplars based on Ardelt's three-dimensional wisdom model. RESULTS: Of the 61 physicians interviewed, 33 (54%) were male, and on average, eight years had elapsed since the error. Wisdom exemplars were more likely to report disclosing the error to the patient/family (69%) than nonexemplars (38%); P < .03. Fewer than 10% of all participants reported receiving disclosure training. Investigators identified eight themes reflecting what helped physician wisdom exemplars cope positively: talking about it, disclosure and apology, forgiveness, a moral context, dealing with imperfection, learning/becoming an expert, preventing recurrences/improving teamwork, and helping others/teaching. CONCLUSIONS: The path forged by doctors who coped well with medical error highlights specific ways to help clinicians move through this difficult experience so that they avoid devastating professional outcomes and have the best chance of not just recovery but positive growth. PMID- 26352765 TI - Solvent-assisted headspace sampling using solid phase microextraction for the analysis of phenols in water. AB - Headspace analysis is used widely and relies on volatilization of analytes into the headspace above the matrix. We detail the dramatic influence that added solvent can have on headspace analysis of phenols, without the requirement for specialized headspace vials. The use of water-immiscible solvents is key and leads to a 1-3 orders of magnitude enhancement in the volatilization of these analytes and shorter fiber exposure times than are otherwise required. PMID- 26352767 TI - Letter From the Editor: The return of the emperor. PMID- 26352766 TI - Visible-light-driven Ag/AgCl plasmonic photocatalysts via a surfactant-assisted protocol: enhanced catalytic performance by morphology evolution from near spherical to 1D structures. AB - Ag/AgCl-based plasmonic photocatalysts have received much attention as emerging visible-light-driven photocatalysts, wherein those characterized by 1D morphology have aroused great expectations. Most of the current existing protocols for the fabrication of 1D materials, however, suffer from either multistep tedious synthesis processes or the requirement of rigorous experimental conditions. A one pot fabrication method feasible under ambient conditions is strongly desired. By means of a surfactant-assisted protocol, we report herein that Ag/AgCl structures of near-spherical and 1D morphology could be controllably produced. We show that near-spherical Ag/AgCl species could be produced immediately after dropping an AgNO3 aqueous solution into an aqueous solution of cetyltrimethylammonium chloride (CTAC) surfactant under stirring. Interestingly, we show that these initially formed near-spherical species could automatically evolve into 1D Ag/AgCl fibers simply by extending the stirring time under ambient conditions. In our new protocol, CTAC works not only as a chlorine source but also as a directing reagent to assist the formation of 1D Ag/AgCl structures. Moreover, we demonstrate that compared to near-spherical structures, our Ag/AgCl fibers could display boosted catalytic performances towards the photodegradation of the methyl orange pollutant under visible light irradiation. Our work might launch an easy method for the construction of fibrous Ag/AgCl architectures of superior photocatalytic reactivity, and it also provides deep insights into the surfactant assisted synthesis. PMID- 26352768 TI - Monitoring lymphoma patients after therapy. PMID- 26352769 TI - Combining inhibitors of ALK and ROS1 with other agents for the treatment of non small cell lung cancer. PMID- 26352770 TI - PARP inhibitors in ovarian and other cancers. PMID- 26352771 TI - The new paradigm for transfusion of platelets. PMID- 26352772 TI - Counterpoints: Which should be used first in symptomatic metastatic castration resistant prostate cancer, docetaxel or radium? Docetaxel still the optimal first choice for symptomatic metastatic castration-resistant prostate cancer. PMID- 26352773 TI - Counterpoints: Which should be used first in symptomatic metastatic castration resistant prostate cancer, docetaxel or radium? Radium-223 is the preferred therapy in bone-predominant symptomatic metastatic castration-resistant prostate cancer. PMID- 26352774 TI - Cancer immunology for the clinician. AB - Cancer immunotherapy is coming of age. It has become abundantly clear that immunotherapy-which has been described as treating the body's immune system so the immune system can treat the cancer-can be routinely effective, and may indeed cure advanced cancers. Accordingly, it is important to understand the basic, clinically relevant principles of cancer immunology to better prepare for an increasingly exciting future. The host immune system is the only active enemy faced by a malignant cell population as it develops. So it is helpful to think of the battle between the cancer cell population and the developing cancer as a Darwinian crucible in which only the malignant cells most fit to thrive in the face of active immune system attack are able to survive in the reluctant host. All successful cancers thus have overcome the defenses mounted by host immune systems by actively thwarting the evolution of anticancer immunity. A malignant cell population that has "solved" the riddle of the host immune system need not employ all of these mechanisms in order to survive in a particular host. Hence, it may be that the dominant mechanism or mechanisms of immune evasion in fact represent potential Achilles' heels that can be therapeutically attacked to restore immune control of a cancer. To better understand where opportunities exist for immunotherapy, it is important to first consider how developing cancers overcome host immunity: by overwhelming, hiding from, subverting, shielding from, defending against, and outlasting the host immune response. Clearly, more than one of these mechanisms may be present in any particular patient, but it is likely that many cancer types employ dominant immune defense mechanisms. There can be no doubt that mobilizing the immune system to attack a cancer, remember the enemy, and continually target emerging clones represents an extremely promising path to cancer prevention and cure. PMID- 26352775 TI - Non-clear cell renal cell carcinoma, part 1: histology. AB - Non-clear cell renal cell carcinomas (RCCs) represent up to 20% of all RCCs. Despite often being clustered as a single entity, these tumors represent a heterogeneous group of diseases with distinct molecular drivers, histologies, and clinical outcomes. Their low incidence and heterogeneity have resulted in a lack of studies that address the optimal strategies for each subtype. This article (the first in a 2-part series) reviews the histology of RCC, whereas the second article reviews current targeted therapies approved for RCC, such as the vascular endothelial growth factor receptor tyrosine kinase inhibitors and the mammalian target of rapamycin inhibitors. Ongoing studies will provide more information regarding the role of these agents in non-clear cell RCC. PMID- 26352777 TI - How we treat systemic light-chain amyloidosis. AB - Systemic light-chain (AL) amyloidosis is a multisystem disease characterized by organ toxicity and damage due to monoclonal free light chains, which are produced by a neoplastic clone of plasma cells in bone marrow. Current treatment strategies target the clone in order to decrease the production of the pathologic light chains and thereby stop or reverse organ toxicity and damage. AL amyloidosis remains a formidable and often incurable disease despite treatment options that include corticosteroids, cytotoxic chemotherapy, risk-adapted melphalan, autologous hematopoietic stem cell transplantation, proteasome inhibitors, and immunomodulatory drugs. New and effective treatment approaches that can reverse the organ damage are urgently needed. Physicians and clinical staff should be aware of the importance of providing best supportive care to patients with advanced AL-related organ dysfunction, given the patients' often tenuous hemodynamics and fragile functional status. Organ transplantation has a role in selected clinical situations, and the treating hematologist should be aware of this sometimes-useful option. PMID- 26352778 TI - Kidney Cancer Update The year in review in kidney cancer. PMID- 26352779 TI - Antibiotic prescribing trends in necrotising otitis externa: a survey of 85 trusts in the United Kingdom: Our Experience. PMID- 26352780 TI - A Vanadium Dioxide Metamaterial Disengaged from Insulator-to-Metal Transition. AB - We report that vanadium dioxide films patterned with lambda/100000 nanogaps exhibit an anomalous transition behavior at millimeter wavelengths. Most of the hybrid structure's switching actions occur well below the insulator to metal transition temperature, starting from 25 degrees C, so that the hysteresis curves completely separate themselves from their bare film counterparts. It is found that thermally excited intrinsic carriers are responsible for this behavior by introducing enough loss in the context of the radically modified electromagnetic environment in the vicinity of the nanogaps. This phenomenon newly extends the versatility of insulator to metal transition devices to encompass their semiconductor properties. PMID- 26352781 TI - Ewald Electrostatics for Mixtures of Point and Continuous Line Charges. AB - Many charged macro- or supramolecular systems, such as DNA, are approximately rod shaped and, to the lowest order, may be treated as continuous line charges. However, the standard method used to calculate electrostatics in molecular simulation, the Ewald summation, is designed to treat systems of point charges. We extend the Ewald concept to a hybrid system containing both point charges and continuous line charges. We find the calculated force between a point charge and (i) a continuous line charge and (ii) a discrete line charge consisting of uniformly spaced point charges to be numerically equivalent when the separation greatly exceeds the discretization length. At shorter separations, discretization induces deviations in the force and energy, and point charge-point charge correlation effects. Because significant computational savings are also possible, the continuous line charge Ewald method presented here offers the possibility of accurate and efficient electrostatic calculations. PMID- 26352783 TI - Adjusting Antidepressant Quality Measures for Race and Ethnicity. PMID- 26352782 TI - Defective heat shock factor 1 inhibits the growth of fibrosarcoma derived from simian virus 40/T antigen-transformed MEF cells. AB - Heat shock factor 1 (Hsf1) serves an important role in regulating the proliferation of human tumor cell lines in vitro and tissue specific tumorigenesis in certain mouse models. However, its role in viral-oncogenesis remains to be fully elucidated. In the current study, the role of Hsf1 in fibroblastoma derived from simian virus 40/T antigen (SV40/TAG)-transformed mouse embryonic fibroblast (MEF) cell lines was investigated. Knockout of Hsf1 inhibited MEF cell proliferation in vitro and fibroblastoma growth and metastasis to the lungs in vivo in nude mice. Knockout of Hsf1 increased the protein expression levels of p53 and phosphorylated retinoblastoma protein (pRb), however reduced the expression of heat shock protein 25 (Hsp25) in addition to the expression of the angiogenesis markers vascular endothelial growth factor, cluster of differentiation 34 and factor VIII related antigen. Furthermore, immunoprecipitation indicated that knockout of Hsf1 inhibited the association between SV40/TAG and p53 or pRb. These data suggest that Hsf1 is involved in the regulation of SV40/TAG-derived fibroblastoma growth and metastasis by modulating the association between SV40/TAG and tumor suppressor p53 and pRb. The current study provides further evidence that Hsf1 may be a novel therapeutic target in the treatment of cancer. PMID- 26352784 TI - Identification and clinical relevance of PD-L1 expression in primary mucosal malignant melanoma of the head and neck. AB - Mucosal melanoma of the head and neck is a rare and aggressive tumor entity with a poor prognosis. The standard treatment is radical tumor resection, with or without adjuvant radiation, where conventional chemotherapies in advanced stage or recurrent diseases have shown little benefit. Overexpression of the programmed cell death ligand 1 (PD-L1) is a common feature in human cancer. Although PD-L1 is an acknowledged prognostic biomarker for dismal prognosis in other tumors of the head and neck, expression and clinical relevance of PD-L1 in mucosal melanoma have not been addressed so far. We assessed PD-L1 expression using immunohistochemical staining in 23 tumor samples from patients with primary mucosal melanoma and correlated expression status with clinicopathological and outcome data. Tumors were derived from the nasal cavity (43.5%), nasal sinuses (43.5%), and the conjunctiva (13%). All patients had undergone surgery; 39% of all patients received adjuvant radiation and 13% were administered systemic interferon therapy. The probability of 1- and 5-year overall survival was 87 and 34.8%, respectively. The mean overall survival was 51 months and the mean recurrence-free survival was 23 months. Immunohistochemical staining showed PD-L1 expression in 13% (3/23) of mucosal melanoma. In contrast, prominent PD-L1 staining was detected in 100% of tissue sections from a control group of cutaneous melanoma (n=9). PD-L1 expression in mucosal melanoma was not correlated with age, sex, nor anatomical localization of the tumor. Interestingly, patients with PD-L1-positive mucosal melanoma had a significantly longer recurrence-free survival (P=0.026). In contrast to cutaneous melanoma and some other malignancies, a relevant PD-L1 overexpression in mucosal melanoma could not be confirmed. PMID- 26352786 TI - Differences in motor learning of pelvic floor muscle contraction between women with and without stress urinary incontinence: Evaluation by transabdominal ultrasonography. AB - AIMS: To evaluate differences in motor learning of pelvic floor muscle (PFM) contraction between women with and without stress urinary incontinence (SUI) under transabdominal ultrasonography (TAUS)-guided PFM training. METHODS: Postpartum women received an intensive 3-month PFM training program from 3 to 6 months postpartum. The program consisted of home exercises and weekly group sessions with individual TAUS-guided training. Motor learning progress of PFM contraction was evaluated with TAUS at each weekly session. We regarded a woman who contracted her PFM correctly more than 9 times out of the 10 repetitions as having achieved the associative stage of motor learning. Women were evaluated before and after a 12-week intervention for PFM and SUI by using transperineal ultrasonography and questionnaire, respectively. RESULTS: Seventy-three women were included: 44 primiparous women (60.3%) and 64 vaginal deliveries (87.7%). Of 73 women, 22 (30.1%) were classified as the SUI group. By the fifth session, the proportion of women who could correctly contract their PFM > 9 out of the 10 repetitions had increased significantly more in the non-SUI group than in the SUI group (90.0% vs. 58.8%, P = 0.011). The proportion of women achieving the associative stage of correct PFM contraction was not different between the two groups after the sixth session. PF morphology and SUI were improved after intervention (P < 0.05). CONCLUSIONS: The proportion of women achieving the associative stage in women with SUI was less than that in women without SUI in the early phase of the combination of group and home PFM training with TAUS guided training. Neurourol. Urodynam. 36:98-103, 2017. (c) 2015 Wiley Periodicals, Inc. PMID- 26352785 TI - Transcription factors regulating B cell fate in the germinal centre. AB - Diversification of the antibody repertoire is essential for the normal operation of the vertebrate adaptive immune system. Following antigen encounter, B cells are activated, proliferate rapidly and undergo two diversification events; somatic hypermutation (followed by selection), which enhances the affinity of the antibody for its cognate antigen, and class-switch recombination, which alters the effector functions of the antibody to adapt the response to the challenge faced. B cells must then differentiate into antibody-secreting plasma cells or long-lived memory B cells. These activities take place in specialized immunological environments called germinal centres, usually located in the secondary lymphoid organs. To complete the germinal centre activities successfully, a B cell adopts a transcriptional programme that allows it to migrate to specific sites within the germinal centre, proliferate, modify its DNA recombination and repair pathways, alter its apoptotic potential and finally undergo terminal differentiation. To co-ordinate these processes, B cells employ a number of 'master regulator' transcription factors which mediate wholesale transcriptomic changes. These master transcription factors are mutually antagonistic and form a complex regulatory network to maintain distinct gene expression programs. Within this network, multiple points of positive and negative feedback ensure the expression of the 'master regulators', augmented by a number of 'secondary' factors that reinforce these networks and sense the progress of the immune response. In this review we will discuss the different activities B cells must undertake to mount a successful T cell-dependent immune response and describe how a regulatory network of transcription factors controls these processes. PMID- 26352787 TI - Energy and Emissions from U.S. Population Shifts and Implications for Regional GHG Mitigation Planning. AB - Living in different areas is associated with different impacts; the movement of people to and from those areas will affect energy use and emissions over the U.S. The emissions implications of state-to-state migration on household energy and GHG emissions are explored. Three million households move across state lines annually, and generally move from the North East to the South and West. Migrating households often move to states with different climates (thus different heating and cooling and needs), different fuel mixes, and different regional electricity grids, which leads them to experience changes in household emissions as a result of their move. Under current migration trends, the emissions increases of households moving from the Northeast to the South and Southwest are balanced by the emissions decreases of households moving to California and the Pacific Northwest. The net sum of emissions changes for migrating households is slightly positive but near zero; however, that net zero sum represents the balance of many emission changes. Planning for continued low carbon growth in low carbon regions or cities experiencing high growth rates driven by migration is essential in order to offset the moderate emissions increases experienced by households moving to high carbon regions. PMID- 26352788 TI - Controlled Embedding of Metal Oxide Nanoparticles in ZSM-5 Zeolites through Preencapsulation and Timed Release. AB - We report a straightforward and transferrable synthesis strategy to encapsulate metal oxide nanoparticles (NPs) in mesoporous ZSM-5 via the encapsulation of NPs into silica followed by conversion of the NP@silica precursor to NP@ZSM-5. The systematic bottom-up approach allows for straightforward, precise control of both the metal weight loading and size of the embedded NP and yields uniform NP@ZSM-5 microspheres composed of stacked ZSM-5 nanorods with substantial mesoporosity. Key to the synthesis is the timed release of the embedded NPs during dissolution of the silica matrix in the hydrothermal conversion step, which finely balances the rate of NP release with the rate of SiO2 dissolution and the subsequent nucleation of aluminosilicate. The synthesis approach is demonstrated for Zn, Fe, and Ni oxide encapsulation in ZSM-5 but can be expected to be broadly transferrable for the encapsulation of metal and metal oxide nanoparticles into other zeolite structures. PMID- 26352789 TI - The management and prognosis of patients with hepatocellular carcinoma: what has changed in 20 years? AB - BACKGROUND & AIMS: There has been remarkable progress in the management of hepatocellular carcinoma (HCC) during the last several decades, but its effect on the prognosis of HCC patient needs clarification. We analysed the changes that affected prognosis of HCC patients diagnosed over two different eras. METHODS: A retrospective study of 1318 patients diagnosed with HCC from 1986 to 2012 was conducted. Analysis was done according to two cohorts, cohort 1 (patients diagnosed with HCC from 1986 to 1992) and cohort 2 (patients diagnosed from 2006 to 2012). RESULTS: Hepatitis B virus was the most common cause of liver disease for both cohorts (66.2% and 66.0%). The proportion of patients with Barcelona Clinic Liver Cancer stage 0/A was significantly lower in cohort 1 than in cohort 2 (14.4% vs. 39.5%, P < 0.001). The proportions of patients diagnosed during surveillance and general health check-up were significantly higher in cohort 2 than in cohort 1 (28.6% vs. 10.6% and 26.3% vs. 7.9%, respectively) while those diagnosed during symptomatic evaluation was significantly higher in cohort 1 than in cohort 2 (45.1 vs. 81.4%, P < 0.001). Surgical resection rate was similar between the two cohorts (26.1% vs 26%) while the transcatheter arterial chemoembolization rate which was the highest in cohort 1 (40.6%) was overtaken by radiofrequency ablation in cohort 2 (55%) at BCLC stage 0/A. Median survival duration in cohort 2 was significantly longer than cohort 1 (65.0 vs. 7.9 months, P < 0.001). CONCLUSIONS: Implementation of national cancer surveillance and the advancement of treatment modalities have likely led to early detection of HCC and improvements in prognosis over the last 20 years. PMID- 26352790 TI - Multi-lineage potential research of bone marrow mesenchymal stem cells from Bama miniature pig. AB - Bone marrow mesenchymal stem cells (BMSCs) are easy to obtain and thought to be ideal candidate cells for reconstruction of tissues and organs. Pigs are an appropriate animal model because their physiological structure, organ size, nutritional metabolism, and pathological reactions are similar to those of humans. In this study, bone marrow was collection from Bama miniature pigs to isolate BMSCs (B-BMSCs) by whole bone marrow culture method. We then examined their biological characteristics such as growth kinetics, surface antigen, and multi-lineage potential. B-BMSCs could be cultured for 36 passages in vitro. Growth kinetics and colony forming assay analyses indicated that B-BMSCs had a strong capacity for self-renewal in vitro and their proliferation rate appeared to decrease with passaging. These findings were supported by the animal cytophysiology in vitro. Surface antigen detection showed that B-BMSCs expressed CD29, CD44, CD71, CD73, and CD90, but not the endothelial cell marker CD31 or hematopoietic cell-specific marker CD34. This result was consistent with the characteristics of B-BMSCs. Furthermore, under appropriate conditions for multidirectional differentiation, B-BMSCs were induced to differentiate into adipocytes, osteoblasts, neuron-like cells, islet cells, liver-like cells, and endothelial cells as indicated by reverse transcription-polymerase chain reaction (RT-PCR) and immunofluorescence. These results verified the differentiation potential of B-BMSCs. In this study, B-BMSCs were isolated from Bama miniature pigs, and the self-renewal ability and differential potential was evaluated in vitro. The present study has important bearing on the potential application of B BMSCs as a stem cell source for regenerative therapies. J. Exp. Zool. (Mol. Dev. Evol.) 324B: 671-685, 2015. (c) 2015 Wiley Periodicals, Inc. PMID- 26352791 TI - Expression and promoter methylation of Wnt inhibitory factor-1 in the development of oral submucous fibrosis. AB - Oral squamous cell carcinoma (OSCC) is a type of head and neck malignancy with a high mortality rate. Oral submucous fibrosis (OSF) is the pre-cancerous lesion of OSCC, whose molecular mechanisms in OSCC tumorigenesis remain largely unclear. Activation of the Wnt/beta-catenin signaling pathway plays an important role in oral mucous carcinogenesis, although rare mutations of Wnt signaling molecules are found in OSCC, suggesting an epigenetic mechanism mediating aberrant Wnt/beta catenin signaling in OSCC. Wnt inhibitory factor-1 (WIF1) is an Wnt antagonist, and its downregulation and methylation have been reported in a number of malignancies. However, the expression and methylation of WIF1 in the development of OSF have yet to be reported. In the present study, we investigated the WIF1 expression level by immuno-histochemical staining and semi-quantitative RT-PCR in normal oral, OSF and OSCC tissues, as well as the methylation status by methylation-specific PCR and bisulfite genomic sequencing. The results showed that WIF1 was readily expressed in normal oral mucous tissues, but decreased gradually in OSF early, moderately advanced and advanced tissues, and was less expressed in OSCC tissues. Moreover, WIF1 was able to translocate from the nuclear to cytoplasm in OSF and OSCC tissues. Furthermore, WIF1 was frequently methylated in OSCC cases with betel quid chewing habit, but not in normal oral mucous and different stages of OSF tissues, suggesting WIF1 methylation is tumor specific in the development of OSF. Thus, the results demonstrated that WIF1 is frequently downregulated or silenced by promoter methylation in the carcinogenesis of OSF, which serves as a potential epigenetic biomarker for the early detection of OSCC. PMID- 26352792 TI - Persistence of Abeta seeds in APP null mouse brain. AB - Cerebral beta-amyloidosis is induced by inoculation of Abeta seeds into APP transgenic mice, but not into App(-/-) (APP null) mice. We found that brain extracts from APP null mice that had been inoculated with Abeta seeds up to 6 months previously still induced beta-amyloidosis in APP transgenic hosts following secondary transmission. Thus, Abeta seeds can persist in the brain for months, and they regain propagative and pathogenic activity in the presence of host Abeta. PMID- 26352793 TI - Refractive Outcomes, Contrast Sensitivity, HOAs, and Patient Satisfaction in Moderate Myopia: Wavefront-Optimized Versus Tissue-Saving PRK. AB - PURPOSE: To compare refractive outcomes, contrast sensitivity, higher-order aberrations (HOAs), and patient satisfaction after photorefractive keratectomy for correction of moderate myopia with two methods: tissue saving versus wavefront optimized. METHODS: In this prospective, comparative study, 152 eyes (80 patients) with moderate myopia with and without astigmatism were randomly divided into two groups: the tissue-saving group (Technolas 217z Zyoptix laser; Bausch & Lomb, Rochester, NY) (76 eyes of 39 patients) or the wavefront-optimized group (WaveLight Allegretto Wave Eye-Q laser; Alcon Laboratories, Inc., Fort Worth, TX) (76 eyes of 41 patients). Preoperative and 3-month postoperative refractive outcomes, contrast sensitivity, HOAs, and patient satisfaction were compared between the two groups. RESULTS: The mean spherical equivalent was -4.50 +/- 1.02 diopters. No statistically significant differences were detected between the groups in terms of uncorrected and corrected distance visual acuity and spherical equivalent preoperatively and 3 months postoperatively. No statistically significant differences were seen in the amount of preoperative to postoperative contrast sensitivity changes between the two groups in photopic and mesopic conditions. HOAs and Q factor increased in both groups postoperatively (P = .001), with the tissue-saving method causing more increases in HOAs (P = .007) and Q factor (P = .039). Patient satisfaction was comparable between both groups. CONCLUSIONS: Both platforms were effective in correcting moderate myopia with or without astigmatism. No difference in refractive outcome, contrast sensitivity changes, and patient satisfaction between the groups was observed. Postoperatively, the tissue-saving method caused a higher increase in HOAs and Q factor compared to the wavefront-optimized method, which could be due to larger optical zone sizes in the tissue-saving group. PMID- 26352794 TI - Noradrenergic and cholinergic modulation of late ERP responses to deviant stimuli. AB - Researchers have proposed several hypotheses about the neuromodulator systems involved in generating P3 components of the ERP. To test some of these hypotheses, we conducted a randomized placebo-controlled crossover study in which we investigated how the late positive ERP response to deviant stimuli is modulated by (a) clonidine, an alpha2 agonist that attenuates baseline noradrenergic activity; and (b) scopolamine, a muscarinic antagonist of acetylcholine receptors. We collected EEG data from 18 healthy volunteers during the performance of an auditory oddball task with several active and passive task conditions. We then used temporospatial principal component analysis (PCA) to decompose the ERP waveforms. The PCA revealed two distinct late positive ERP components: the classic parietal P300 and the frontal novelty P3. Statistical analysis of the temporospatial factor scores indicated that in most conditions the amplitude of the classic P300 was increased by clonidine and scopolamine. In contrast, the amplitude of the novelty P3 was decreased by both drugs. The similar pattern of results for clonidine and scopolamine probably reflects the strong interactions between the noradrenergic and cholinergic systems. The results, in combination with previous pharmacological studies, suggest a critical role for both neuromodulator systems in the generation of the P300 and the novelty P3. PMID- 26352795 TI - Rational design of selective small-molecule inhibitors for beta-catenin/B-cell lymphoma 9 protein-protein interactions. AB - Selective inhibition of alpha-helix-mediated protein-protein interactions (PPIs) with small organic molecules provides great potential for the discovery of chemical probes and therapeutic agents. Protein Data Bank data mining using the HippDB database indicated that (1) the side chains of hydrophobic projecting hot spots at positions i, i + 3, and i + 7 of an alpha-helix had few orientations when interacting with the second protein and (2) the hot spot pockets of PPI complexes had different sizes, shapes, and chemical groups when interacting with the same hydrophobic projecting hot spots of alpha-helix. On the basis of these observations, a small organic molecule, 4'-fluoro-N-phenyl-[1,1'-biphenyl]-3 carboxamide, was designed as a generic scaffold that itself directly mimics the binding mode of the side chains of hydrophobic projecting hot spots at positions i, i + 3, and i + 7 of an alpha-helix. Convenient decoration of this generic scaffold led to the selective disruption of alpha-helix-mediated PPIs. A series of small-molecule inhibitors selective for beta-catenin/B-cell lymphoma 9 (BCL9) over beta-catenin/cadherin PPIs was designed and synthesized. The binding mode of new inhibitors was characterized by site-directed mutagenesis and structure activity relationship studies. This new class of inhibitors can selectively disrupt beta-catenin/BCL9 over beta-catenin/cadherin PPIs, suppress the transactivation of canonical Wnt signaling, downregulate the expression of Wnt target genes, and inhibit the growth of Wnt/beta-catenin-dependent cancer cells. PMID- 26352796 TI - Metal-Free C-Arylation of Nitro Compounds with Diaryliodonium Salts. AB - An efficient, mild, and metal-free arylation of nitroalkanes with diaryliodonium salts has been developed, giving easy access to tertiary nitro compounds. The reaction proceeds in high yields without the need for excess reagents and can be extended to alpha-arylation of nitroesters. Nitroalkanes were selectively C arylated in the presence of other easily arylated functional groups, such as phenols and aliphatic alcohols. PMID- 26352797 TI - AAIRS Score Overview: The Acute Asthma Intensity Research Score. PMID- 26352798 TI - Human Satellite Cell Transplantation and Regeneration from Diverse Skeletal Muscles. AB - Identification of human satellite cells that fulfill muscle stem cell criteria is an unmet need in regenerative medicine. This hurdle limits understanding how closely muscle stem cell properties are conserved among mice and humans and hampers translational efforts in muscle regeneration. Here, we report that PAX7 satellite cells exist at a consistent frequency of 2-4 cells/mm of fiber in muscles of the human trunk, limbs, and head. Xenotransplantation into mice of 50 70 fiber-associated, or 1,000-5,000 FACS-enriched CD56(+)/CD29(+) human satellite cells led to stable engraftment and formation of human-derived myofibers. Human cells with characteristic PAX7, CD56, and CD29 expression patterns populated the satellite cell niche beneath the basal lamina on the periphery of regenerated fibers. After additional injury, transplanted satellite cells robustly regenerated to form hundreds of human-derived fibers. Together, these findings conclusively delineate a source of bona-fide endogenous human muscle stem cells that will aid development of clinical applications. PMID- 26352799 TI - Conditionally Stabilized dCas9 Activator for Controlling Gene Expression in Human Cell Reprogramming and Differentiation. AB - CRISPR/Cas9 protein fused to transactivation domains can be used to control gene expression in human cells. In this study, we demonstrate that a dCas9 fusion with repeats of VP16 activator domains can efficiently activate human genes involved in pluripotency in various cell types. This activator in combination with guide RNAs targeted to the OCT4 promoter can be used to completely replace transgenic OCT4 in human cell reprogramming. Furthermore, we generated a chemically controllable dCas9 activator version by fusion with the dihydrofolate reductase (DHFR) destabilization domain. Finally, we show that the destabilized dCas9 activator can be used to control human pluripotent stem cell differentiation into endodermal lineages. PMID- 26352800 TI - Structures of Pseudomonas aeruginosa LpxA Reveal the Basis for Its Substrate Selectivity. AB - In Gram-negative bacteria, the first step of lipid A biosynthesis is catalyzed by UDP-N-acetylglucosamine acyltransferase (LpxA) through the transfer of a R-3 hydroxyacyl chain from the acyl carrier protein (ACP) to the 3-hydroxyl group of UDP-GlcNAc. Previous studies suggest that LpxA is a critical determinant of the acyl chain length found in lipid A, which varies among species of bacteria. In Escherichia coli and Leptospira interrogans, LpxA prefers to incorporate longer R 3-hydroxyacyl chains (C14 and C12, respectively), whereas in Pseudomonas aeruginosa, the enzyme is selective for R-3-hydroxydecanoyl, a 10-hydrocarbon long acyl chain. We now report three P. aeruginosa LpxA crystal structures: apo protein, substrate complex with UDP-GlcNAc, and product complex with UDP-3-O-(R-3 hydroxydecanoyl)-GlcNAc. A comparison between the apo form and complexes identifies key residues that position UDP-GlcNAc appropriately for catalysis and supports the role of catalytic His121 in activating the UDP-GlcNAc 3-hydroxyl group for nucleophilic attack during the reaction. The product-complex structure, for the first time, offers structural insights into how Met169 serves to constrain the length of the acyl chain and thus functions as the so-called hydrocarbon ruler. Furthermore, compared with ortholog LpxA structures, the purported oxyanion hole, formed by the backbone amide group of Gly139, displays a different conformation in P. aeruginosa LpxA, which suggests flexibility of this structural feature important for catalysis and the potential need for substrate induced conformational change in catalysis. Taken together, the three structures provide valuable insights into P. aeruginosa LpxA catalysis and substrate specificity as well as templates for future inhibitor discovery. PMID- 26352801 TI - SNAILs promote G1 phase in selected cancer cells. AB - Cells can acquire a stem-like cell phenotype through epithelial-mesenchymal transition (EMT). However, it is not known which of the stem-like cancer cells are generated by these phenotype transitions. We studied the EMT-inducing roles of SNAILs (the key inducers for the onset of EMT) in selected cancer cells (lung cancer cell line with relatively stable genome), in order to provide more implications for the investigation of EMT-related phenotype transitions in cancer. However, SNAILs fail to induce completed EMT. In addition, we proved that Snail accelerates the early G1 phase whereas Slug accelerates the late G1 phase. Blocking G1 phase is one of the basic conditions for the onset of EMT-related phenotype transitions (e.g., metastasis, acquiring stemness). The discovery of this unexpected phenomenon (promoting G1 phase) typically reveals the heterogeneity of cancer cells. The onset of EMT-related phenotype transitions in cancer needs not only the induction and activation of SNAILs, but also some particular heredity alterations (genetic or epigenetic alterations, which cause heterogeneity). The new connection between heredity alteration (heterogeneity) and phenotype transition suggests a novel treatment strategy, the heredity alteration-directed specific target therapy. Further investigations need to be conducted to study the relevant heredity alterations. PMID- 26352803 TI - Intramolecular Photoreactions of (5S)-5-Oxymethyl-2(5H)-furanones as a Tool for the Stereoselective Generation of Diverse Polycyclic Scaffolds. AB - The photoactivated evolution of a series of enantiomerically pure 5-oxymethyl 2(5H)-furanones has been investigated. The observed intramolecular photoreactions have proven to be a straightforward entry to diverse and stereochemically rich fragment-molecules, most of which contain the privileged tetrahydropyran (THP) scaffold. The formation of the THP involves a 1,5-hydrogen atom transfer process, leading to a diradical intermediate that recombines to form a new sigma C-C bond. These reactions take place under both sensitized and nonsensitized conditions, and they are highly stereoselective. When the substrate contains an allyl residue, the intramolecular [2 + 2] cycloaddition leading to cyclobutanes competes advantageously. When the substrate contains a THP residue, the cyclization involves the concomitant formation of [6,6]-spiroketals with nonanomeric relationships. PMID- 26352802 TI - The Impact of Selective Dopamine D2, D3 and D4 Ligands on the Rat Gambling Task. AB - Gambling is an addictive disorder with serious societal and personal costs. To date, there are no approved pharmacological treatments for gambling disorder. Evidence suggests a role for dopamine in gambling disorder and thus may provide a therapeutic target. The present study therefore aimed to investigate the effects of selective antagonists and agonists of D2, D3 and D4 receptors in a rodent analogue of the Iowa gambling task used clinically. In this rat gambling task (rGT), animals are trained to associate different response holes with different magnitudes and probabilities of food pellet rewards and punishing time-out periods. As in the Iowa gambling task, the optimal strategy is to avoid the tempting high-risk high-reward options, and instead favor those linked to smaller per-trial rewards but also lower punishments, thereby maximizing the amount of reward earned over time. Administration of those selective ligands did not affect decision making under the rGT. Only the D4 drug had modest effects on latency measures suggesting that D4 may contribute in some ways to decision making under this task. PMID- 26352804 TI - Wheat NAC transcription factor TaNAC29 is involved in response to salt stress. AB - Soil salinity is considered as one of the most severe abiotic stress factors, which limit plant growth and cause significant losses in crop yield. NAC transcription factors have been proven to play vital roles in abiotic stress signaling in plants. As a staple crop, wheat production is severely constrained by salt stress whereas only a few NAC genes have been characterized functionally. To promote the application of NAC genes in wheat improvement by genetic engineering, a NAC gene designated TaNAC29 was characterized in common wheat. Expression analysis showed that TaNAC29 gene was involved in response to salt, drought and ABA treatments. TaNAC29 protein displays transactivation activity. To determine its role, transgenic Arabidopsis overexpressing TaNAC29 controlled by the CaMV-35S promoter was generated and subjected to salt stress for morphological and physiological assays. Morphological analysis showed that transgenic plants had enhanced tolerance to salt stress, as indicated by improved physiological traits, including more green leaves, reduced H2O2 accumulation, strengthened cell membrane stability and higher SOD, POD, CAT and APX activities. Moreover, the transcript levels of stress-related genes were significantly higher in TaNAC29 overexpression line than those in WT under salt treatment. Taken together, our results demonstrate that TaNAC29 confers salt stress tolerance through reducing H2O2 accumulation and membrane damage by enhancing the antioxidant system, and participating in regulating the abiotic stress-responsive signaling pathway. PMID- 26352805 TI - Lactobacillus fermentum CECT 5716 Reduces Staphylococcus Load in the Breastmilk of Lactating Mothers Suffering Breast Pain: A Randomized Controlled Trial. AB - INTRODUCTION: Recent results indicate that human mastitis and painful breastfeeding may be characterized by a mammary bacterial dysbiosis, a process in which the population of potential pathogens increases at the expense of the normal mammary microbiota. The objective of the present study is the evaluation of three different doses of Lactobacillus fermentum CECT5716 to reduce the load of Staphylococcus in the breastmilk of women suffering from painful breastfeeding. MATERIALS AND METHODS: A randomized double-blinded controlled study with four study groups was performed. Three groups received the probiotic strain for 3 weeks at doses of 3*10(9) colony-forming units (CFU)/day, 6*10(9) CFU/day, or 9*10(9) CFU/day. The fourth group received a placebo of maltodextrin. The main outcome of the study was Staphylococcus counts in breastmilk. The secondary outcomes were Streptococcus, Lactobacillus, and total bacteria counts in breastmilk, immunoglobulin A and interleukin 8 concentrations in breastmilk, and breast pain scores. RESULTS: At the end of the study, a significant decrease in the Staphylococcus load was observed in the probiotic groups compared with the baseline loads (p=0.045), whereas the control group maintained similar levels over time. A significant difference in the pain score was observed among the groups receiving the three probiotic doses compared with the control group (p=0.035, p=0.000, and p=0.028, respectively). A dose-response effect could not be observed because the three doses tested induced similar effects, and no significant differences were detected. CONCLUSIONS: We conclude that L. fermentum CECT5716 is an efficient treatment for breast pain during lactation associated with a high level of Staphylococcus in breastmilk. PMID- 26352806 TI - Separation of thorium ions from wolframite and scandium concentrates using graphene oxide. AB - The separation of rare metals from the ores and commercially available compounds is an important issue due to the need of their high purity in advanced materials and devices. Important examples of two highly important elements that co-exist in the ores are scandium and thorium. Scandium containing ores and consequently also commercially available scandium compounds often contain traces of thorium which is very difficult to separate. We used graphene oxide for the selective sorption of thorium ions from scandium and thorium mixtures originating from the mined ores as well as from commercially available scandium salts. Our results showed that graphene oxide has an extreme affinity towards thorium ions. After the sorption process the graphene oxide contained over 20 wt% of thorium while the amount of scandium sorbed on GO was very low. This phenomenon of high sorption selectivity of graphene oxide can be applied in industry for the purification of various chemicals containing scandium and for separation of thorium containing mixtures. Alternatively, this methodology can be used for preconcentration of thorium from low-grade ores and its further use in the new generation of nuclear reactors. PMID- 26352807 TI - A Genetic Selection for dinB Mutants Reveals an Interaction between DNA Polymerase IV and the Replicative Polymerase That Is Required for Translesion Synthesis. AB - Translesion DNA synthesis (TLS) by specialized DNA polymerases (Pols) is a conserved mechanism for tolerating replication blocking DNA lesions. The actions of TLS Pols are managed in part by ring-shaped sliding clamp proteins. In addition to catalyzing TLS, altered expression of TLS Pols impedes cellular growth. The goal of this study was to define the relationship between the physiological function of Escherichia coli Pol IV in TLS and its ability to impede growth when overproduced. To this end, 13 novel Pol IV mutants were identified that failed to impede growth. Subsequent analysis of these mutants suggest that overproduced levels of Pol IV inhibit E. coli growth by gaining inappropriate access to the replication fork via a Pol III-Pol IV switch that is mechanistically similar to that used under physiological conditions to coordinate Pol IV-catalyzed TLS with Pol III-catalyzed replication. Detailed analysis of one mutant, Pol IV-T120P, and two previously described Pol IV mutants impaired for interaction with either the rim (Pol IVR) or the cleft (Pol IVC) of the beta sliding clamp revealed novel insights into the mechanism of the Pol III-Pol IV switch. Specifically, Pol IV-T120P retained complete catalytic activity in vitro but, like Pol IVR and Pol IVC, failed to support Pol IV TLS function in vivo. Notably, the T120P mutation abrogated a biochemical interaction of Pol IV with Pol III that was required for Pol III-Pol IV switching. Taken together, these results support a model in which Pol III-Pol IV switching involves interaction of Pol IV with Pol III, as well as the beta clamp rim and cleft. Moreover, they provide strong support for the view that Pol III-Pol IV switching represents a vitally important mechanism for regulating TLS in vivo by managing access of Pol IV to the DNA. PMID- 26352808 TI - Adiponectin-Mediated Analgesia and Anti-Inflammatory Effects in Rat. AB - The adipose tissue-derived protein, adiponectin, has significant anti inflammatory properties in a variety of disease conditions. Recent evidence that adiponectin and its receptors (AdipoR1 and AdipoR2) are expressed in central nervous system, suggests that it may also have a central modulatory role in pain and inflammation. This study set out to investigate the effects of exogenously applied recombinant adiponectin (via intrathecal and intraplantar routes; 10-5000 ng) on the development of peripheral inflammation (paw oedema) and pain hypersensitivity in the rat carrageenan model of inflammation. Expression of adiponectin, AdipoR1 and AdipoR2 mRNA and protein was characterised in dorsal spinal cord using real-time polymerase chain reaction (PCR) and Western blotting. AdipoR1 and AdipoR2 mRNA and protein were found to be constitutively expressed in dorsal spinal cord, but no change in mRNA expression levels was detected in response to carrageenan-induced inflammation. Adiponectin mRNA, but not protein, was detected in dorsal spinal cord, although levels were very low. Intrathecal administration of adiponectin, both pre- and 3 hours post-carrageenan, significantly attenuated thermal hyperalgesia and mechanical hypersensitivity. Intrathecal administration of adiponectin post-carrageenan also reduced peripheral inflammation. Intraplantar administration of adiponectin pre carrageenan dose-dependently reduced thermal hyperalgesia but had no effect on mechanical hypersensitivity and peripheral inflammation. These results show that adiponectin functions both peripherally and centrally at the spinal cord level, likely through activation of AdipoRs to modulate pain and peripheral inflammation. These data suggest that adiponectin receptors may be a novel therapeutic target for pain modulation. PMID- 26352809 TI - Endoscopic management of familial adenomatous polyposis in patients refusing colectomy. AB - BACKGROUND AND STUDY AIMS: Colectomy protects against colorectal cancer in familial adenomatous polyposis (FAP); however, some patients with FAP refuse surgery. The aim of this study was to evaluate the feasibility and safety of endoscopic management of these patients. PATIENTS AND METHODS: A retrospective review of medical records was performed to identify adult patients with FAP who refused colectomy and were managed by repeated colonoscopies to remove numerous polyps between 2001 and 2012. Polyps were removed by hot snare polypectomy or endoscopic mucosal resection. Polyps of < 10 mm in size and without endoscopic features suggesting cancer were discarded without histological examination; the remaining polyps were examined histologically. RESULTS: Of the 95 eligible patients, five (5.3 %) were excluded. The remaining 90 patients (median age at first visit 29 years [range 16 - 68 years]; 46 males) were followed for a median of 5.1 years (interquartile range [IQR] 3.3 - 7.3 years). During this period, a total of 55 701 polyps were resected without adverse events such as bleeding or perforation. The median numbers of endoscopic treatment sessions and polyps removed per patient were 8 (IQR 6 - 11) and 475 (IQR 211 - 945), respectively. Five patients had noninvasive carcinoma (Category 4.2 according to the revised Vienna classification), detected within 10 months from the start of the follow-up period. All of these patients were treated endoscopically, without signs of recurrence during a median follow-up of 4.3 years (IQR 2.0 - 7.1 years). No invasive colorectal cancer was recorded during the study period. Two patients (2.2 %) underwent colectomy because the polyposis phenotype had changed to dense polyposis. CONCLUSION: Endoscopic management of FAP is feasible and safe in the medium term. PMID- 26352810 TI - Pharmacokinetic and Pharmacodynamic Characterisation of an Anti-Mouse TNF Receptor 1 Domain Antibody Formatted for In Vivo Half-Life Extension. AB - Tumour Necrosis Factor-alpha (TNF-alpha) inhibition has been transformational in the treatment of patients with inflammatory disease, e.g. rheumatoid arthritis. Intriguingly, TNF-alpha signals through two receptors, TNFR1 and TNFR2, which have been associated with detrimental inflammatory and beneficial immune regulatory processes, respectively. To investigate if selective TNFR1 inhibition might provide benefits over pan TNF-alpha inhibition, tools to investigate the potential impact of pharmacological intervention are needed. Receptor-deficient mice have been very insightful, but are not reversible and could distort receptor cross-talk, while inhibitory anti-TNFR1 monoclonal antibodies have a propensity to induce receptor agonism. Therefore, we set out to characterise a monovalent anti-TNFR1 domain antibody (dAb) formatted for in vivo use. The mouse TNFR1 antagonist (DMS5540) is a genetic fusion product of an anti-TNFR1 dAb with an albumin-binding dAb (AlbudAb). It bound mouse TNFR1, but not human TNFR1, and was an antagonist of TNF-alpha-mediated cytotoxicity in a L929 cell assay. Surprisingly, the dAb did not compete with TNF-alpha for TNFR1-binding. This was supported by additional data showing the anti-TNFR1 epitope mapped to a single residue in the first domain of TNFR1. Pharmacokinetic studies of DMS5540 in mice over three doses (0.1, 1.0 and 10 mg/kg) confirmed extended in vivo half-life, mediated by the AlbudAb, and demonstrated non-linear clearance of DMS5540. Target engagement was further confirmed by dose-dependent increases in total soluble TNFR1 levels. Functional in vivo activity was demonstrated in a mouse challenge study, where DMS5540 provided dose-dependent inhibition of serum IL-6 increases in response to bolus mouse TNF-alpha injections. Hence, DMS5540 is a potent mouse TNFR1 antagonist with in vivo pharmacokinetic and pharmacodynamic properties compatible with use in pre-clinical disease models and could provide a useful tool to dissect the individual contributions of TNFR1 and TNFR2 in homeostasis and disease. PMID- 26352811 TI - Medicine's Wild West--Unlicensed Stem-Cell Clinics in the United States. PMID- 26352812 TI - Medicare's Vision for Delivery-System Reform--The Role of ACOs. PMID- 26352813 TI - A Phase 3 Trial of Sebelipase Alfa in Lysosomal Acid Lipase Deficiency. AB - BACKGROUND: Lysosomal acid lipase is an essential lipid-metabolizing enzyme that breaks down endocytosed lipid particles and regulates lipid metabolism. We conducted a phase 3 trial of enzyme-replacement therapy in children and adults with lysosomal acid lipase deficiency, an underappreciated cause of cirrhosis and severe dyslipidemia. METHODS: In this multicenter, randomized, double-blind, placebo-controlled study involving 66 patients, we evaluated the safety and effectiveness of enzyme-replacement therapy with sebelipase alfa (administered intravenously at a dose of 1 mg per kilogram of body weight every other week); the placebo-controlled phase of the study was 20 weeks long and was followed by open-label treatment for all patients. The primary end point was normalization of the alanine aminotransferase level. Secondary end points included additional disease-related efficacy assessments, safety, and side-effect profile. RESULTS: Substantial disease burden at baseline included a very high level of low-density lipoprotein cholesterol (>=190 mg per deciliter) in 38 of 66 patients (58%) and cirrhosis in 10 of 32 patients (31%) who underwent biopsy. A total of 65 of the 66 patients who underwent randomization completed the double-blind portion of the trial and continued with open-label treatment. At 20 weeks, the alanine aminotransferase level was normal in 11 of 36 patients (31%) in the sebelipase alfa group and in 2 of 30 (7%) in the placebo group (P=0.03), with mean changes from baseline of -58 U per liter versus -7 U per liter (P<0.001). With respect to prespecified key secondary efficacy end points, we observed improvements in lipid levels and reduction in hepatic fat content (P<0.001 for all comparisons, except P=0.04 for triglycerides). The number of patients with adverse events was similar in the two groups; most events were mild and were considered by the investigator to be unrelated to treatment. CONCLUSIONS: Sebelipase alfa therapy resulted in a reduction in multiple disease-related hepatic and lipid abnormalities in children and adults with lysosomal acid lipase deficiency. (Funded by Synageva BioPharma and others; ARISE ClinicalTrials.gov number, NCT01757184.). PMID- 26352814 TI - Eculizumab in Pregnant Patients with Paroxysmal Nocturnal Hemoglobinuria. AB - BACKGROUND: Eculizumab, a humanized monoclonal antibody against complement protein C5 that inhibits terminal complement activation, has been shown to prevent complications of paroxysmal nocturnal hemoglobinuria (PNH) and improve quality of life and overall survival, but data on the use of eculizumab in women during pregnancy are scarce. METHODS: We designed a questionnaire to solicit data on pregnancies in women with PNH and sent it to the members of the International PNH Interest Group and to the physicians participating in the International PNH Registry. We assessed the safety and efficacy of eculizumab in pregnant patients with PNH by examining the birth and developmental records of the children born and adverse events in the mothers. RESULTS: Of the 94 questionnaires that were sent out, 75 were returned, representing a response rate of 80%. Data on 75 pregnancies in 61 women with PNH were evaluated. There were no maternal deaths and three fetal deaths (4%). Six miscarriages (8%) occurred during the first trimester. Requirements for transfusion of red cells increased during pregnancy, from a mean of 0.14 units per month in the 6 months before pregnancy to 0.92 units per month during pregnancy. Platelet transfusions were given in 16 pregnancies. In 54% of pregnancies that progressed past the first trimester, the dose or the frequency of use of eculizumab had to be increased. Low-molecular weight heparin was used in 88% of the pregnancies. Ten hemorrhagic events and 2 thrombotic events were documented; both thrombotic events occurred during the postpartum period. A total of 22 births (29%) were premature. Twenty cord-blood samples were examined for the presence of eculizumab; the drug was detected in 7 of the samples. A total of 25 babies were breast-fed, and in 10 of these cases, breast milk was examined for the presence of eculizumab; the drug was not detected in any of the 10 breast-milk samples. CONCLUSIONS: Eculizumab provided benefit for women with PNH during pregnancy, as evidenced by a high rate of fetal survival and a low rate of maternal complications. (ClinicalTrials.gov number, NCT01374360.). PMID- 26352815 TI - Chimeric Antigen Receptor T Cells against CD19 for Multiple Myeloma. AB - A patient with refractory multiple myeloma received an infusion of CTL019 cells, a cellular therapy consisting of autologous T cells transduced with an anti-CD19 chimeric antigen receptor, after myeloablative chemotherapy (melphalan, 140 mg per square meter of body-surface area) and autologous stem-cell transplantation. Four years earlier, autologous transplantation with a higher melphalan dose (200 mg per square meter) had induced only a partial, transient response. Autologous transplantation followed by treatment with CTL019 cells led to a complete response with no evidence of progression and no measurable serum or urine monoclonal protein at the most recent evaluation, 12 months after treatment. This response was achieved despite the absence of CD19 expression in 99.95% of the patient's neoplastic plasma cells. (Funded by Novartis and others; ClinicalTrials.gov number, NCT02135406.). PMID- 26352816 TI - Cannabinoids in the Treatment of Epilepsy. PMID- 26352817 TI - IMAGES IN CLINICAL MEDICINE. A Viper Bite. PMID- 26352818 TI - CASE RECORDS of the MASSACHUSETTS GENERAL HOSPITAL. Case 28-2015. A 32-Year-Old Man with Fever, Headache, and Myalgias after Traveling from Liberia. PMID- 26352819 TI - Lysosomal Acid Lipase Deficiency--A New Therapy for a Genetic Lipid Disease. PMID- 26352821 TI - Stent-Retriever Thrombectomy for Stroke. PMID- 26352822 TI - Stent-Retriever Thrombectomy for Stroke. PMID- 26352823 TI - Trends in Mental Health Care among Children and Adolescents. PMID- 26352824 TI - Trends in Mental Health Care among Children and Adolescents. PMID- 26352825 TI - Trends in Mental Health Care among Children and Adolescents. PMID- 26352826 TI - Squamous Change in Basal-Cell Carcinoma with Drug Resistance. PMID- 26352827 TI - Carbon Monoxide Poisoning Due to "Mud Bogging". PMID- 26352828 TI - IMAGES IN CLINICAL MEDICINE. Arachnoid Cyst. PMID- 26352820 TI - Stent-Retriever Thrombectomy for Stroke. PMID- 26352829 TI - Transcriptional Analysis of the Conjugal Transfer Genes of Rickettsia bellii RML 369-C. AB - Rickettsia bellii is an obligate intracellular bacterium that is one of the few rickettsiae that encode a complete set of conjugative transfer (tra) genes involved in bacterial conjugation and has been shown to exhibit pili-like structures. The reductive genomes of rickettsiae beg the question whether the tra genes are nonfunctional or functioning to enhance the genetic plasticity and biology of rickettsiae. We characterized the transcriptional dynamics of R. bellii tra genes in comparison to genes transcribed stably and above the background level to understand when and at what levels the tra genes are active or whether the tra genes are degenerative. We determined that the best reference genes, out of 10 tested, were methionyl tRNA ligase (metG) or a combination of metG and ribonucleoside diphosphate reductase 2 subunit beta (nrdF), using statistical algorithms from two different programs: Normfinder and BestKeeper. To validate the use of metG with other rickettsial genes exhibiting variable transcriptional patterns we examined its use with sca2 and rickA, genes involved in actin based motility. Both were shown to be up-regulated at different times of replication in Vero cells, showing variable and stable transcription levels of rickA and sca2, respectively. traATi was up-regulated at 72 hours post inoculation in the tick cell line ISE6, but showed no apparent changes in the monkey cell line Vero and mouse cell line L929. The transcription of tra genes was positively correlated with one another and up-regulated from 12 to 72 hours post inoculation (HPI) when compared to RBE_0422 (an inactivated transposase derivative found within the tra cluster). Thus, the up-regulation of the tra genes indicated that the integrity and activity of each gene were intact and may facilitate the search for the optimal conditions necessary to demonstrate conjugation in rickettsiae. PMID- 26352830 TI - Comparative studies on the chemical and enzymatic stability of alpha- and beta arbutin. AB - OBJECTIVE: The aim of this study was to establish a comparative analysis of the chemical and enzymatic stability of alpha- and beta-arbutins as potential sources of the substance of concern hydroquinone (HQ). The study was performed using an array of techniques including HPLC-PDA, nuclear magnetic resonance (NMR) and optical rotation (OR). Both arbutins are emerging as popular and effective skin whiteners, acting as tyrosinase inhibitors in a fashion similar to the popular whitening agent HQ. Due to their structural similarity to the regulated agent HQ, both arbutins may be regarded as potential sources of the active aglycone after chemical or metabolic conversion. METHODS: Various cosmetic formulations including creams, sera, gels and lotions were analysed by HPLC-PDA for their arbutin and HQ content in freshly opened and aged samples stored for 16 months. Solutions of pure compounds were also aged and periodically checked for degradation products using 1D and 2D NMR experiments and OR measurements. The metabolic stability was investigated using pear peels as a biological model. RESULTS: Both arbutins were found to be stable in water and methanol solutions in the absence of buffer or stabilizers. Their stability in cosmetic formulations, however, was found to depend on the type of formulation and pH. Both compounds were unstable under strong hydrolytic conditions, with consequent release of HQ. Enzymatic instability of both arbutins was also observed, although no formation of HQ was observed under the chosen experimental conditions. CONCLUSION: Both arbutins were found to possess similar stability profiles, and to be more prone to in vivo rather than in chemico degradation, although no HQ was found after enzymatic hydrolysis. Also, no epimerization was observed in any of the tested conditions. Diverse experimental approaches can be applied to analyse the chemical and enzymatic stability of arbutins in regard to the potential release of HQ in different types of preparations. These result showed the potential use of NMR and OR as complementary investigative tools for the stability and safety assessment of arbutin along with more established HPLC methods. PMID- 26352831 TI - Complete Genome Sequence of a High Lipid-Producing Strain of Mucor circinelloides WJ11 and Comparative Genome Analysis with a Low Lipid-Producing Strain CBS 277.49. AB - The genome of a high lipid-producing fungus Mucor circinelloides WJ11 (36% w/w lipid, cell dry weight, CDW) was sequenced and compared with that of the low lipid-producing strain, CBS 277.49 (15% w/w lipid, CDW), which had been sequenced by Joint Genome Institute. The WJ11 genome assembly size was 35.4 Mb with a G+C content of 39.7%. The general features of WJ11 and CBS 277.49 indicated that they have close similarity at the level of gene order and gene identity. Whole genome alignments with MAUVE revealed the presence of numerous blocks of homologous regions and MUMmer analysis showed that the genomes of these two strains were mostly co-linear. The central carbon and lipid metabolism pathways of these two strains were reconstructed and the numbers of genes encoding the enzymes related to lipid accumulation were compared. Many unique genes coding for proteins involved in cell growth, carbohydrate metabolism and lipid metabolism were identified for each strain. In conclusion, our study on the genome sequence of WJ11 and the comparative genomic analysis between WJ11 and CBS 277.49 elucidated the general features of the genome and the potential mechanism of high lipid accumulation in strain WJ11 at the genomic level. The different numbers of genes and unique genes involved in lipid accumulation may play a role in the high oleaginicity of strain WJ11. PMID- 26352833 TI - Determining the Role of Dynamic Hyperinflation in Patients with Severe Chronic Obstructive Pulmonary Disease. AB - BACKGROUND: Dynamic hyperinflation due to increased respiratory frequency during exercise is associated with limitations in exercise capacity in patients with moderately severe chronic obstructive pulmonary disease (COPD). OBJECTIVES: The present study assessed whether the manually paced tachypnea (MPT) test, sitting at rest, induces dynamic hyperinflation correlating with exercise capacity in patients with very severe COPD. METHODS: Dynamic hyperinflation was induced by the MPT test, using a breathing frequency of 40/min for 1 min. Dynamic hyperinflation was defined as a 'change' in inspiratory capacity (IC) before and directly after the MPT test. At baseline, static hyperinflation by body plethysmography was measured, as well as the 6-min walking test and spirometry. RESULTS: We studied 74 patients with severe COPD (age 59 +/- 9 years, FEV1 28 +/- 10% predicted). All patients tolerated the MPT test well. It induced a significant decrease in IC: -0.65 +/- 0.33 liters, p < 0.001, correlating with the 6-min walking distance (rho = -0.246, p = 0.034). Static hyperinflation [IC/total lung capacity (TLC)] at baseline correlated stronger with the 6-min walking distance (r = 0.582, p < 0.001). Multiple regression analysis showed that IC/TLC, but not dynamic hyperinflation, was the only independent predictor of walking distance. CONCLUSIONS: In patients with very severe COPD, dynamic hyperinflation measurement by the MPT test is feasible and contributes less importantly to exercise performance than static hyperinflation. PMID- 26352834 TI - Persistent, Nontender Lip Swelling in a Patient With HIV. PMID- 26352832 TI - Correlation of Culture Positivity, PCR Positivity, and Burden of Borrelia burgdorferi Sensu Lato in Skin Samples of Erythema Migrans Patients with Clinical Findings. AB - BACKGROUND: Limited data are available regarding the relationship of Borrelia burden in skin of patients with erythema migrans (EM) and the disease course and post-treatment outcome. METHODS: We studied 121 adult patients with EM in whom skin biopsy specimens were cultured and analyzed by quantitative PCR for the presence of Borreliae. Evaluation of clinical and microbiological findings were conducted at the baseline visit, and 14 days, 2, 6, and 12 months after treatment with either amoxicillin or cefuroxime axetil. RESULTS: In 94/121 (77.7%) patients Borrelia was detected in skin samples by PCR testing and 65/118 (55.1%) patients had positive skin culture result (96.8% B. afzelii, 3.2% B. garinii). Borrelia culture and PCR results correlated significantly with the presence of central clearing and EM size, while Borrelia burden correlated significantly with central clearing, EM size, and presence of newly developed or worsened symptoms since EM onset, with no other known medical explanation (new or increased symptoms, NOIS). In addition, the logistic regression model for repeated measurements adjusted for time from inclusion, indicated higher Borrelia burden was a risk factor for incomplete response (defined as NOIS and/or persistence of EM beyond 14 days and/or occurrence of new objective signs of Lyme borreliosis). The estimated association between PCR positivity and unfavorable outcome was large but not statistically significant, while no corresponding relationship was observed for culture positivity. CONCLUSIONS: Higher Borrelia burden in EM skin samples was associated with more frequent central clearing and larger EM lesions at presentation, and with a higher chance of incomplete response. PMID- 26352835 TI - Sandwich fluorimetric method for specific detection of Staphylococcus aureus based on antibiotic-affinity strategy. AB - A novel antibiotic-affinity strategy was designed for fluorimetric detection of pathogenic bacteria based on the strong affinity of antibiotic agent to the cell wall of bacteria. In this proof-of-concept work, vancocin, a glycopeptide antibiotic for Gram-positive bacteria, was used as a molecular recognition agent to anchor Staphylococcus aureus (S. aureus) cell. To improve the specificity of this method for S. aureus detection, IgG was adopted as the second recognition agent utilizing the binding between Fc region of IgG and S. aureus protein A in the cell wall, to form a sandwich complex. By using fluorescein isothiocyanate as the signal probe, S. aureus whole cells could be directly assayed within a linear range of 1.0 * 10(3)-1.0 * 10(9) CFU mL(-1) with a detection limit of 2.9 * 10(2) CFU mL(-1). The whole assay process could be completed within 130 min when a ready-for-use microplate was adopted. This proposed strategy for pathogenic bacteria detection possessed some attractive characteristics such as high sensitivity, wide linear range, simple manipulation, short assay time, and low cost. Furthermore, this sandwich mode also showed ideal specificity because vancocin and IgG bound with S. aureus at two distinct sites. It opened up a new pathway for high-throughput screening of pathogenic bacteria in medical diagnosis, food safety, bioterrorism defense, and drug discovery. PMID- 26352836 TI - Bumblebee Homing: The Fine Structure of Head Turning Movements. AB - Changes in flight direction in flying insects are largely due to roll, yaw and pitch rotations of their body. Head orientation is stabilized for most of the time by counter rotation. Here, we use high-speed video to analyse head- and body movements of the bumblebee Bombus terrestris while approaching and departing from a food source located between three landmarks in an indoor flight-arena. The flight paths consist of almost straight flight segments that are interspersed with rapid turns. These short and fast yaw turns ("saccades") are usually accompanied by even faster head yaw turns that change gaze direction. Since a large part of image rotation is thereby reduced to brief instants of time, this behavioural pattern facilitates depth perception from visual motion parallax during the intersaccadic intervals. The detailed analysis of the fine structure of the bees' head turning movements shows that the time course of single head saccades is very stereotypical. We find a consistent relationship between the duration, peak velocity and amplitude of saccadic head movements, which in its main characteristics resembles the so-called "saccadic main sequence" in humans. The fact that bumblebee head saccades are highly stereotyped as in humans, may hint at a common principle, where fast and precise motor control is used to reliably reduce the time during which the retinal images moves. PMID- 26352838 TI - Correction: Web-based evaluation of experts' opinions on impacted maxillary canines forced eruption using CBCT. PMID- 26352837 TI - Elevated Levels of Cytokines Associated with Th2 and Th17 Cells in Vitreous Fluid of Proliferative Diabetic Retinopathy Patients. AB - Macrophages are involved in low-grade inflammation in diabetes, and play pathogenic roles in proliferative diabetic retinopathy (PDR) by producing proinflammatory cytokines. T cells as well as other cells are also activated by proinflammatory cytokines, and infiltration into the vitreous of patients with PDR has been shown. In this study, we measured helper T (Th) cell-related cytokines in the vitreous of PDR patients to define the characteristics of Th mediated immune responses associated with PDR. The study group consisted of 25 type 2 diabetic patients (25 eyes) with PDR. The control group consisted of 27 patients with epiretinal membrane (ERM), 26 patients with idiopathic macular hole (MH), and 26 patients with uveitis associated with sarcoidosis. Vitreous fluid was obtained at the beginning of vitrectomy, and centrifuging for cellular removals was not performed. Serum was also collected from PDR patients. IL-1beta, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, IFN gamma, soluble sCD40L, and TNFalpha in the vitreous and serum samples were measured. Both percent detectable and levels of IL-4, IL-6, IL-17A, IL-21, IL-22, and TNFalpha in the vitreous were significantly higher than those in the serum in PDR patients. Vitreous levels of these cytokines and IL-31 were significantly higher in PDR than in ERM or MH patients. Vitreous levels of IL-4, IL-17A, IL-22, IL-31, and TNFalpha in PDR patients were also significantly higher than those of sarcoidosis patients. In PDR patients, vitreous IL-17A level correlated significantly with vitreous levels of IL-22 and IL-31, and especially with IL-4 and TNFalpha. Although it is unclear whether these cytokines play facilitative roles or inhibitory roles for the progression of PDR, the present study indicated that Th2- and Th17-related immune responses are involved in the pathogenesis of PDR. PMID- 26352839 TI - Third molars: To extract or not to extract? PMID- 26352840 TI - What is the level of evidence of what you are reading? PMID- 26352841 TI - An interview with Alvaro Alfredo Figueroa. PMID- 26352842 TI - Color stability of ceramic brackets immersed in potentially staining solutions. AB - OBJECTIVE: To assess the color stability of five types of ceramic brackets after immersion in potentially staining solutions. METHODS: Ninety brackets were divided into 5 groups (n = 18) according to brackets commercial brands and the solutions in which they were immersed (coffee, red wine, coke and artificial saliva). The brackets assessed were Transcend (3M/Unitek, Monrovia, CA, USA), Radiance (American Orthodontics, Sheboygan, WI, USA), Mystique (GAC International Inc., Bohemia, NY, USA) and Luxi II (Rocky Mountain Orthodontics, Denver, CO, USA). Chromatic changes were analyzed with the aid of a reflectance spectrophotometer and by visual inspection at five specific time intervals. Assessment periods were as received from the manufacturer (T0), 24 hours (T1), 72 hours (T2), as well as 7 days (T3) and 14 days (T4) of immersion in the aforementioned solutions. Results were submitted to statistical analysis with ANOVA and Bonferroni correction, as well as to a multivariate profile analysis for independent and paired samples with significance level set at 5%. RESULTS: The duration of the immersion period influenced color alteration of all tested brackets, even though these changes could not always be visually observed. Different behaviors were observed for each immersion solution; however, brackets immersed in one solution progressed similarly despite minor variations. CONCLUSIONS: Staining became more intense over time and all brackets underwent color alterations when immersed in the aforementioned solutions. PMID- 26352843 TI - Guidelines proposal for clinical recognition of mouth breathing children. AB - INTRODUCTION: Mouth breathing (MB) is an etiological factor for sleep-disordered breathing (SDB) during childhood. The habit of breathing through the mouth may be perpetuated even after airway clearance. Both habit and obstruction may cause facial muscle imbalance and craniofacial changes. OBJECTIVE: The aim of this paper is to propose and test guidelines for clinical recognition of MB and some predisposing factors for SDB in children. METHODS: Semi-structured interviews were conducted with 110 orthodontists regarding their procedures for clinical evaluation of MB and their knowledge about SDB during childhood. Thereafter, based on their answers, guidelines were developed and tested in 687 children aged between 6 and 12 years old and attending elementary schools. RESULTS: There was no standardization for clinical recognition of MB among orthodontists. The most common procedures performed were inefficient to recognize differences between MB by habit or obstruction. CONCLUSIONS: The guidelines proposed herein facilitate clinical recognition of MB, help clinicians to differentiate between habit and obstruction, suggest the most appropriate treatment for each case, and avoid maintenance of mouth breathing patterns during adulthood. PMID- 26352844 TI - Evaluation of stiffness and plastic deformation of active ceramic self-ligating bracket clips after repetitive opening and closure movements. AB - OBJECTIVE: The aim of this study was to assess whether repetitive opening and closure of self-ligating bracket clips can cause plastic deformation of the clip. METHODS: Three types of active/interactive ceramic self-ligating brackets (n = 20) were tested: In-Ovation C, Quicklear and WOW. A standardized controlled device performed 500 cycles of opening and closure movements of the bracket clip with proper instruments and techniques adapted as recommended by the manufacturer of each bracket type. Two tensile tests, one before and one after the repetitive cycles, were performed to assess the stiffness of the clips. To this end, a custom-made stainless steel 0.40 x 0.40 mm wire was inserted into the bracket slot and adapted to the universal testing machine (EMIC DL2000), after which measurements were recorded. On the loading portion of the loading-unloading curve of clips, the slope fitted a first-degree equation curve to determine the stiffness/deflection rate of the clip. RESULTS: The results of plastic deformation showed no significant difference among bracket types before and after the 500 cycles of opening and closure (p = 0.811). There were significant differences on stiffness among the three types of brackets (p = 0.005). The WOW bracket had higher mean values, whereas Quicklear bracket had lower values, regardless of the opening/closure cycle. CONCLUSION: Repetitive controlled opening and closure movements of the clip did not alter stiffness or cause plastic deformation. PMID- 26352845 TI - Four chemical methods of porcelain conditioning and their influence over bond strength and surface integrity. AB - OBJECTIVE: To assess four different chemical surface conditioning methods for ceramic material before bracket bonding, and their impact on shear bond strength and surface integrity at debonding. METHODS: Four experimental groups (n = 13) were set up according to the ceramic conditioning method: G1 = 37% phosphoric acid etching followed by silane application; G2 = 37% liquid phosphoric acid etching, no rinsing, followed by silane application; G3 = 10% hydrofluoric acid etching alone; and G4 = 10% hydrofluoric acid etching followed by silane application. After surface conditioning, metal brackets were bonded to porcelain by means of the Transbond XP system (3M Unitek). Samples were submitted to shear bond strength tests in a universal testing machine and the surfaces were later assessed with a microscope under 8 X magnification. ANOVA/Tukey tests were performed to establish the difference between groups (alpha= 5%). RESULTS: The highest shear bond strength values were found in groups G3 and G4 (22.01 +/- 2.15 MPa and 22.83 +/- 3.32 Mpa, respectively), followed by G1 (16.42 +/- 3.61 MPa) and G2 (9.29 +/- 1.95 MPa). As regards surface evaluation after bracket debonding, the use of liquid phosphoric acid followed by silane application (G2) produced the least damage to porcelain. When hydrofluoric acid and silane were applied, the risk of ceramic fracture increased. CONCLUSIONS: Acceptable levels of bond strength for clinical use were reached by all methods tested; however, liquid phosphoric acid etching followed by silane application (G2) resulted in the least damage to the ceramic surface. PMID- 26352846 TI - Evaluation of an alternative technique to optimize direct bonding of orthodontic brackets to temporary crowns. AB - OBJECTIVE: To compare shear bond strength of different direct bonding techniques of orthodontic brackets to acrylic resin surfaces. METHODS: The sample comprised 64 discs of chemically activated acrylic resin (CAAR) randomly divided into four groups: discs in group 1 were bonded by means of light-cured composite resin (conventional adhesive); discs in group 2 had surfaces roughened with a diamond bur followed by conventional direct bonding by means of light-cured composite resin; discs in group 3 were bonded by means of CAAR (alternative adhesive); and discs in group 4 had surfaces roughened with a diamond bur followed by direct bonding by means of CAAR. Shear bond strength values were determined after 24 hours by means of a universal testing machine at a speed of 0.5 mm/min, and compared by analysis of variance followed by post-hoc Tukey test. Adhesive remnant index (ARI) was measured and compared among groups by means of Kruskal Wallis and Dunn tests. RESULTS: Groups 3 and 4 had significantly greater shear bond strength values in comparison to groups 1 and 2. Groups 3 and 4 yielded similar results. Group 2 showed better results when compared to group 1. In ARI analyses, groups 1 and 2 predominantly exhibited a score equal to 0, whereas groups 3 and 4 predominantly exhibited a score equal to 3. CONCLUSIONS: Direct bonding of brackets to acrylic resin surfaces using CAAR yielded better results than light-cured composite resin. Surface preparation with diamond bur only increased shear bond strength in group 2. PMID- 26352847 TI - Evaluation of facial morphology and sagittal relationship between dental arches in primary and mixed dentition. AB - OBJECTIVE: To assess facial morphology (Pattern) and sagittal relationship between dental arches (Class), and establish a potential association between them and the variables sex, age and ethnicity, among schoolchildren aged between 4 and 9 years old (mean age of 6.7 years) in primary and mixed dentitions. METHODS: The sample comprised 875 children (457 males and 418 females) attending schools in Descalvado, Sao Paulo, Brazil. An attempt was made with a view to establish a potential association between children's morphological features with sex, age and ethnicity. RESULTS: Descriptive analysis revealed a predominance of facial Pattern I (69.9 %) and Class I (67.4 %). Statistical tests (p < 0.001) showed that Class I was more frequent among Pattern I children, whereas Class II prevailed among Pattern II, and Class III was frequent among Pattern I and III children. Ethnicity was the only variable associated with facial pattern. CONCLUSIONS: Results suggest that facial pattern and sagittal relationship between dental arches tend to be correlated. Ethnicity was associated with facial pattern, with Pattern I being the most recurrent among Caucasians and facial Pattern II being recurrent among Afro-descendant subjects. PMID- 26352848 TI - Craniofacial skeletal pattern: is it really correlated with the degree of adenoid obstruction? AB - OBJECTIVE: The aim of this study was to compare the cephalometric pattern of children with and without adenoid obstruction. METHODS: The sample comprised 100 children aged between four and 14 years old, both males and females, subjected to cephalometric examination for sagittal and vertical skeletal analysis. The sample also underwent nasofiberendoscopic examination intended to objectively assess the degree of adenoid obstruction. RESULTS: The individuals presented tendencies towards vertical craniofacial growth, convex profile and mandibular retrusion. However, there were no differences between obstructive and non-obstructive patients concerning all cephalometric variables. Correlations between skeletal parameters and the percentage of adenoid obstruction were either low or not significant. CONCLUSIONS: Results suggest that specific craniofacial patterns, such as Class II and hyperdivergency, might not be associated with adenoid hypertrophy. PMID- 26352849 TI - Effects of cervical headgear appliance: a systematic review. AB - OBJECTIVE: Although much has been investigated about the effects of cervical headgear, there remains some controversy. Therefore, the objective of this systematic review is to disclose the actual effects of the cervical headgear appliance, based on articles of relevant quality. METHODS: A literature review was conducted using PubMed, Web of Science, Embase, Scopus and Cochrane databases. Inclusion criteria consisted of human studies written in English; published between 1970 and 2014; in which only the cervical headgear was used to correct Class II malocclusion; prospective or retrospective; with a clear description of cervical headgear effects; with a sample size of at least 15 individuals. No comparative studies, clinical cases or cases with dental extractions were included and the sample should be homogeneous. RESULTS: Initially, 267 articles were found. A total of 42 articles were selected by title and had their abstracts read. Finally, 12 articles were classified as with high quality and were used in this systematic review. CONCLUSIONS: The cervical headgear appliance proved efficient to correct Class II, Division 1 malocclusion. Its effects consisted in correction of the maxillomandibular relationship by restriction of maxillary anterior displacement; distalization and extrusion of maxillary molars; and slight maxillary expansion. PMID- 26352850 TI - Orthodontic approach to treat complex hypodontia using miniscrews in a growing patient. AB - This article reports orthodontic treatment of a case of hypodontia of five premolars in an 11-year-old female patient with a positive tooth size-arch length discrepancy in both dental arches. The patient had a straight profile with balanced facial growth. Setup manufacture revealed the possibility of achieving ideal occlusion by mesializing permanent molars up to 15 mm, in addition to keeping a primary molar in the dental arch. With the aid of absolute anchorage, the proposed mechanics was performed and the occlusion predicted in the setup was achieved, while profile and facial growth pattern were maintained. The use of miniscrews for extensive orthodontic movements was successful. Furthermore, one primary molar was extensively mesialized. The indication of gingivoplasty to correct gingival smile proved effective. This is considered a useful technique for orthodontists. PMID- 26352851 TI - Conservative treatment of Angle Class III malocclusion with anterior crossbite. AB - Angle Class III malocclusion is characterized by anteroposterior dental discrepancy which might be associated or not with skeletal changes. Class III molar relationship is associated with vertical or lingually tipped mandibular incisors and a usually concave profile. These characteristics seriously affect facial esthetics and most frequently are the reason why patients seek orthodontic treatment. This case was presented to the committee of the Brazilian Board of Orthodontics and Facial Orthopedics (BBO) as part of the requisites to become a BBO Diplomate. PMID- 26352852 TI - Therapeutic approach to Class II, Division 1 malocclusion with maxillary functional orthopedics. AB - INTRODUCTION: Interceptive treatment of Class II, Division 1 malocclusion is a challenge orthodontists commonly face due to the different growth patterns they come across and the different treatment strategies they have available. OBJECTIVE: To report five cases of interceptive orthodontics performed with the aid of Klammt's elastic open activator (KEOA) to treat Class II, Division 1 malocclusion. METHODS: Treatment comprehends one or two phases; and the use of functional orthopedic appliances, whenever properly recommended, is able to minimize dentoskeletal discrepancies with consequent improvement in facial esthetics during the first stage of mixed dentition. The triad of diagnosis, correct appliance manufacture and patient's compliance is imperative to allow KEOA to contribute to Class II malocclusion treatment. RESULTS: Cases reported herein showed significant improvement in skeletal, dental and profile aspects, as evinced by cephalometric analysis and clinical photographs taken before, during and after interceptive orthodontics. PMID- 26352853 TI - Neurothrombectomy in the Management of Acute Ischemic Stroke. PMID- 26352854 TI - Structured Caregiver Feedback Enhances Engagement and Impact of Mobile Health Support: A Randomized Trial in a Lower-Middle-Income Country. AB - BACKGROUND: Patients' engagement in mobile health (m-health) interventions using interactive voice response (IVR) calls is less in low- and middle-income countries (LMICs) than in industrialized ones. We conducted a study to determine whether automated telephone feedback to informal caregivers ("CarePartners") increased engagement in m-health support among diabetes and hypertension patients in Bolivia. MATERIALS AND METHODS: Patients with diabetes and/or hypertension were identified through ambulatory clinics affiliated with four hospitals. All patients enrolled with a CarePartner. Patients were randomized to weekly IVR calls including self-management questions and self-care education either alone ("standard m-health") or with automated feedback about health and self-care needs sent to their CarePartner after each IVR call ("m-health+CP"). RESULTS: The 72 participants included 39 with diabetes and 53 with hypertension, of whom 19 had <=6 years of education. After 1,225 patient-weeks of attempted IVR assessments, the call completion rate was higher among patients randomized to m-health+CP compared with standard m-health (62.0% versus 44.9%; p < 0.047). CarePartner feedback more than tripled call completion rates among indigenous patients and patients with low literacy (p < 0.001 for both). M-health+CP patients were more likely to report excellent health via IVR (adjusted odds ratio [AOR] = 2.60; 95% confidence interval [CI], 1.07, 6.32) and less likely to report days in bed due to illness (AOR = 0.42; 95% CI, 0.19, 0.91). CONCLUSIONS: In this study we found that caregiver feedback increased engagement in m-health and may improve patients' health status relative to standard approaches. M-health+CP represents a scalable strategy for increasing the reach of self-management support in LMICs. PMID- 26352855 TI - Synthesizing Configurable Biochemical Implementation of Linear Systems from Their Transfer Function Specifications. AB - The ability to engineer synthetic systems in the biochemical context is constantly being improved and has a profound societal impact. Linear system design is one of the most pervasive methods applied in control tasks, and its biochemical realization has been proposed by Oishi and Klavins and advanced further in recent years. However, several technical issues remain unsolved. Specifically, the design process is not fully automated from specification at the transfer function level, systems once designed often lack dynamic adaptivity to environmental changes, matching rate constants of reactions is not always possible, and implementation may be approximative and greatly deviate from the specifications. Building upon the work of Oishi and Klavins, this paper overcomes these issues by introducing a design flow that transforms a transfer-function specification of a linear system into a set of chemical reactions, whose input output response precisely conforms to the specification. This system is implementable using the DNA strand displacement technique. The underlying configurability is embedded into primitive components and template modules, and thus the entire system is adaptive. Simulation of DNA strand displacement implementation confirmed the feasibility and superiority of the proposed synthesis flow. PMID- 26352856 TI - Effectiveness of an Advanced Practice Nurse-Led Preoperative Telephone Assessment. AB - The purpose of this project was to determine the effectiveness of an advanced practice nurse-led preoperative telephone assessment in reducing day-of-surgery cancellations of patients at an ambulatory surgery center. We concluded that a good history obtained by a trained and experienced advanced practice nurse or registered nurse can reduce day-of-surgery cancellations. Patients who were identified at high risk for preoperative complications during the telephone assessment were referred to the preoperative evaluation clinic for further evaluation. PMID- 26352857 TI - Jensen's Inequality and the Impact of Short-Term Environmental Variability on Long-Term Population Growth Rates. AB - It is well established in theory that short-term environmental fluctuations could affect the long-term growth rates of wildlife populations, but this theory has rarely been tested and there remains little empirical evidence that the effect is actually important in practice. Here we develop models to quantify the effects of daily, seasonal, and yearly temperature fluctuations on the average population growth rates, and we apply them to long-term data on the endangered Black-faced Spoonbill (Platalea minor); an endothermic species whose population growth rates follow a concave relationship with temperature. We demonstrate for the first time that the current levels of temperature variability, particularly seasonal variability, are already large enough to substantially reduce long-term population growth rates. As the climate changes, our results highlight the importance of considering the ecological effects of climate variability and not just average conditions. PMID- 26352858 TI - In Response to Letter to the Editor: Cervical Transforaminal with Low-Dose Local Anesthetic Is Not a Safeguard for Neurological Complications. PMID- 26352859 TI - Flow Effects on the Controlled Growth of Nanostructured Networks at Microcapillary Walls for Applications in Continuous Flow Reactions. AB - Low-cost microfluidic devices are desirable for many chemical processes; however, access to robust, inert, and appropriately structured materials for the inner channel wall is severely limited. Here, the shear force within confined microchannels was tuned through control of reactant solution fluid-flow and shown to dramatically impact nano- through microstructure growth. Combined use of experimental results and simulations allowed controlled growth of 3D networked Zn(OH)F nanostructures with uniform pore distributions and large fluid contact areas on inner microchannel walls. These attributes facilitated subsequent preparation of uniformly distributed Pd and PdPt networks with high structural and chemical stability using a facile, in situ conversion method. The advantageous properties of the microchannel based catalytic system were demonstrated using microwave-assisted continuous-flow coupling as a representative reaction. High conversion rates and good recyclability were obtained. Controlling materials nanostructure via fluid-flow-enhanced growth affords a general strategy to optimize the structure of an inner microchannel wall for desired attributes. The approach provides a promising pathway toward versatile, high-performance, and low-cost microfluidic devices for continuous flow chemical processes. PMID- 26352860 TI - Spiromax, a New Dry Powder Inhaler: Dose Consistency under Simulated Real-World Conditions. AB - BACKGROUND: Spiromax((r)) is a novel dry powder inhaler for patients with asthma or chronic obstructive pulmonary disease (COPD). The studies presented here provide further data on attributes (in vitro dosing consistency with budesonide formoterol (DuoResp) Spiromax; flow rates through empty versions of the Spiromax and Turbuhaler inhaler) of importance to patients with asthma or COPD. METHODS: Dose-delivery studies were performed using low-, middle-, and high-strength DuoResp Spiromax. Dose consistency was assessed over inhaler life. Total emitted doses (TEDs) were measured at various flow rates, after exposure to high and low temperature or humidity, at different inhaler orientations, and after dropping the inhaler. The criterion for evaluating dose uniformity was whether mean TEDs were within the product specification limits. In separate studies, flow rates were measured after training, using the patient information leaflets, and again after enhanced training as part of a randomized, open-label, cross-over study. RESULTS: Mean values for both budesonide and formoterol were within 85%-115% of the label claim for each strength of DuoResp Spiromax for initial dose uniformity and for the other investigated conditions (temperature, humidity, orientation, dropping, knocking), with the exception of approximately an 80% increase in first dose after dropping the inhaler (subsequent doses not affected). In the flow rate patient study, two patients' inhalations with Spiromax and six with Turbuhaler were <30 L/min. The majority of asthma patients [91% (Spiromax) versus 82% (Turbuhaler)] achieved the preferred flow rate of >60 L/min. CONCLUSIONS: DuoResp Spiromax consistently meets dose uniformity criteria, under controlled laboratory conditions and with variations intended to mimic real-world use. Following enhanced training, all patients in the flow study were able to achieve the minimal inspiratory flow rate of >30 L/min, which is required for effective treatment. PMID- 26352861 TI - Effect of Paternal Age on Reproductive Outcomes of In Vitro Fertilization. AB - Although the adverse effects of maternal aging on reproductive outcomes have been investigated widely, there is no consensus on the impact of paternal age. Therefore, we investigated the effect of paternal age on reproductive outcomes in a retrospective analysis of 9,991 in vitro fertilization (IVF) cycles performed at the Reproductive Medicine Center of the Third Affiliated Hospital of Guangzhou Medical University (China) between January 2007 and October 2013. Samples were grouped according to maternal age [<30 (3,327 cycles), 30-34 (4,587 cycles), and 35-38 (2,077 cycles)] and then subgrouped according to paternal age (<30, 30-32, 33-35, 36-38, 39-41, and >=42). The groups did not differ in terms of fertilization rate, numbers of viable and high-quality embryos and miscarriage rate when controlling maternal age (P >0.05). Chi-squared analysis revealed that there were no differences in implantation and pregnancy rates among the different paternal age groups when maternal age was <30 and 35-38 years (P >0.05). However, implantation and pregnancy rates decreased with paternal age in the 31-34 y maternal age group (P <0.05). Our study indicates that paternal age has no impact on fertilization rate, embryo quality at the cleavage stage and miscarriage rate. For the 30-34 y maternal age group, the implantation rate decreased with increased paternal age, with the pregnancy rate in this group being significantly higher in the paternal <30 y and 30-32 y age groups, compared with those in the 36-38 y and 39-41 y groups. PMID- 26352862 TI - Genistein enhances TRAIL-induced cancer cell death via inactivation of autophagic flux. AB - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a transmembrane cytokine that is a promising anticancer agent as it selectively induces apoptosis in various types of tumor cells. Autophagic flux, which includes the complete process of autophagy, and suppression of autophagic flux has been increasingly recognized as a favorable and novel therapeutic approach for cancer treatment. Here, we showed that genistein, a major isoflavone compound that exerts its anticancer properties by inhibiting tumor cell proliferation, can induce TRAIL-mediated apoptotic cell death in TRAIL-resistant human adenocarcinoma A549 cells. Notably, genistein treatment led to a marked increase in the accumulation of microtubule-associated protein 1 light chain 3 (LC3)-II and p62 protein levels. The combination of genistein and TRAIL increased LC3-II, p62, activated caspase-3 and activated caspase-8 accumulation, confirming the inhibition of autophagic flux. Taken together, our results revealed that genistein enhanced TRAIL-induced tumor cell death in TRAIL-resistant A549 adenocarcinoma cells by inhibiting autophagic flux. PMID- 26352863 TI - Reduced fat mass and increased lean mass in response to 1 year of melatonin treatment in postmenopausal women: A randomized placebo-controlled trial. AB - OBJECTIVE: Apart from regulating the circadian rhythm, melatonin exerts a variety of actions in the living organism. Among these functions, melatonin is believed to have a positive effect on body weight and energy metabolism. So far, the evidence for this relies mainly on animal models. In this study, we aimed to determine the effects of melatonin on body composition, lipid and glucose metabolism in humans. DESIGN/METHODS: In a double-blind, placebo-controlled study, we randomized 81 postmenopausal women to 1 year of treatment with melatonin (1 or 3 mg nightly) or placebo. Body composition was measured by DXA. Measures were obtained at baseline and after 1 year of treatment along with leptin, adiponectin and insulin. Markers of glucose homeostasis were measured at the end of the study. RESULTS: In response to treatment, fat mass decreased in the melatonin group by 6.9% (95% CI: 1.4%; 12.4%, P = 0.02) compared to placebo. A borderline significant increase in lean mass of 5.2% was found in the melatonin group compared to placebo (3.3%, (IQR:-1.7; 6.2) vs -1.9%, (IQR: -5.7; 5.8), P = 0.08). After adjusting for BMI, lean mass increased by 2.6% (95% CI: 0.1; 5.0, P = 0.04) in the melatonin group. Changes in body weight and BMI did not differ between groups. Adiponectin increased borderline significantly by 21% in the melatonin group compared to placebo (P = 0.08). No significant changes were observed for leptin, insulin or markers of glucose homeostasis. CONCLUSION: Our results suggest a possibly beneficial effect of melatonin on body composition and lipid metabolism as 1 year of treatment reduces fat mass, increases lean mass and is associated with a trend towards an increase in adiponectin. PMID- 26352865 TI - Identification of Di(oxymethylene)glycol in the Raman Spectrum of Formaldehyde Aqueous Solutions by ab Initio Molecular Dynamics Simulations and Quantum Chemistry Calculations. AB - Di(oxymethylene)glycol forms in formaldehyde aqueous solutions by polymerization of methanediol. The structure and hydrogen bond interactions of di(oxymethylene)glycol with water were characterized by performing Car-Parrinello molecular dynamics simulations. The anharmonic vibrational frequencies of di(oxymethylene)glycol in solution were determined with ab initio calculations considering explicitly the hydrogen-bonded water molecules, while other interactions with solvent were described within a polarizable continuum model approach. The calculations allow for a detailed interpretation of the experimental Raman spectrum of formaldehyde aqueous solutions, leading to the assignment of the band at 920 cm(-1) to the symmetric CO stretching mode of di(oxymethylene)glycol. PMID- 26352864 TI - Selective Impairment in Frequency Discrimination in a Mouse Model of Tinnitus. AB - Tinnitus is an auditory disorder, which affects millions of Americans, including active duty service members and veterans. It is manifested by a phantom sound that is commonly restricted to a specific frequency range. Because tinnitus is associated with hearing deficits, understanding how tinnitus affects hearing perception is important for guiding therapies to improve the quality of life in this vast group of patients. In a rodent model of tinnitus, prolonged exposure to a tone leads to a selective decrease in gap detection in specific frequency bands. However, whether and how hearing acuity is affected for sounds within and outside those frequency bands is not well understood. We induced tinnitus in mice by prolonged exposure to a loud mid-range tone, and behaviorally assayed whether mice exhibited a change in frequency discrimination acuity for tones embedded within the mid-frequency range and high-frequency range at 1, 4, and 8 weeks post exposure. A subset of tone-exposed mice exhibited tinnitus-like symptoms, as demonstrated by selective deficits in gap detection, which were restricted to the high frequency range. These mice exhibited impaired frequency discrimination both for tones in the mid-frequency range and high-frequency range. The remaining tone exposed mice, which did not demonstrate behavioral evidence of tinnitus, showed temporary deficits in frequency discrimination for tones in the mid-frequency range, while control mice remained unimpaired. Our findings reveal that the high frequency-specific deficits in gap detection, indicative of tinnitus, are associated with impairments in frequency discrimination at the frequency of the presumed tinnitus. PMID- 26352866 TI - Highly efficient photocatalytic degradation of organic dyes by Cu doped ZnO nanostructures. AB - Copper doped ZnO nanostructures have been synthesized by a facile wet chemical method. Structural properties of as-synthesized nanomaterials have been studied by X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM) and transmission electron microscopy (TEM) with energy dispersive X-ray spectroscopy, while UV-visible absorption spectroscopy and Raman spectroscopy have been used to study their optical properties. Sunlight driven photocatalytic degradation of methylene blue (MB) and methyl orange (MO) dyes in water was used to evaluate the photocatalytic activities of Cu doped ZnO nanostructures using UV visible absorption spectroscopy. The results showed that there is an optimum Cu doping level which leads to the highly enhanced photocatalytic activity of Cu doped ZnO nanostructures, as compared to pure ZnO nanostructures. A mechanism for the enhanced photocatalytic activity of Cu-ZnO nanostructures is tentatively proposed. The enhanced photocatalytic activity of Cu-ZnO nanostructures is attributed to the combined effects of improved separation of photogenerated charge carriers due to optimal Cu doping in ZnO nanostructures and the formation of ZnO-CuO nanoheterojunctions. PMID- 26352867 TI - Redox chemistry of ruthenium ions in mono-substituted Keggin tungstophosphate: a new synthetic extension for ruthenium derivatives based on [PW11O39Ru(VI)N](4.). AB - We herein report the synthesis and characterization of a series of ruthenium substituted Keggin-type heteropolytungstates containing {Ru(II)(NO)}, {Ru(III)(H2O)} or {Ru(IV)Cl} species. Although anionic [PW11O39Ru(II)(NO)](4-) (1) and [PW11O39Ru(III)(H2O)](4-) (2) are known, a new synthetic method for the preparation of (n-Bu4N)4[1] and (n-Bu4N)4[2] is developed in this paper. Treatment of (n-Bu4N)4[XW11O39(Ru[triple bond, length as m-dash]N)] with Me3NO afforded the ruthenium(ii) nitrosyl complex (n-Bu4N)4[1] in almost quantitative yield. Photolysis of (n-Bu4N)4[1] solution in CH3CN/H2O gives (n-Bu4N)4[2], which is readily oxidized by PhICl2 to yield the Ru(IV) complex (n Bu4N)4[PW11O39Ru(IV)Cl] ((n-Bu4N)4[3]). These complexes are fully characterized by (1)H NMR and (31)P NMR spectroscopy, infrared spectroscopy, cyclic voltammetry, elemental analysis, thermogravimetric-differential thermal analysis, electrospray ionization mass spectrometry (ESI-MS) and X-ray photoelectron spectroscopy (XPS). PMID- 26352868 TI - Laboratory Monitoring: A Turning Point in the Use of New Oral Anticoagulants. AB - Large clinical trials have demonstrated that new oral anticoagulants (NOACs) are at least as efficient as vitamin K antagonists (VKAs) in preventing thromboembolic events, while providing a better safety profile. The relatively stable pharmacokinetics and pharmacodynamics, the reduced reports on food and drug interactions, and the wide therapeutic windows of NOACs appear to provide a more predictable anticoagulant effect than that observed with VKAs, enabling the use of fixed doses without the need for monitoring. However, the safe implementation of NOACs may require additional judgment, and one should not have the erroneous impression that NOACs are free from interactions or that inter- and intra-individual variability is absent with NOACs. In fact, a consensus seems to have been reached concerning the usefulness of "circumstantial" testing in certain clinical scenarios. Recent data also suggest that factors such as intercurrent diseases, drug interactions, and inexplicable variability may occasionally alter the anticoagulant effect of NOACs. Furthermore, the issue of nonadherence, already high in VKA-treated patients, may represent an even greater clinical concern with NOACs, given their short half-lives. This review aims to underline the main arguments that support the need for NOAC monitoring, at least in selected categories of patients. Additionally, an overview of classic coagulation assays and novel laboratory techniques that may provide a tool for NOAC monitoring is also provided. PMID- 26352869 TI - Diagnosis and medical and surgical management of cervical spondylotic myelopathy. AB - Cervical spondylotic myelopathy is a complex condition with subtle history and examination findings that mimic other conditions. Primary care physician assistants often are the first providers to evaluate these patients. This article describes cervical spondylotic myelopathy, its diagnosis and management, and recent data that offer strong evidence that patients who undergo surgical decompression show significant improvement over patients who are treated conservatively. PMID- 26352870 TI - Putting intimate partner violence on your radar. AB - Intimate partner violence is a preventable health problem that affects more than 12 million people in the United States each year. Those affected can be of any sex, race, ethnicity, socioeconomic status, religion, education level, or sexual orientation. All clinicians should screen for intimate partner violence as part of the routine history and physical examination. This article describes the dynamics of intimate partner violence and the 2013 screening guidelines from the US Preventive Services Task Force. PMID- 26352871 TI - Upregulation of C-C chemokine receptor type 7 expression by membrane-associated prostaglandin E synthase-1/prostaglandin E2 requires glycogen synthase kinase 3beta-mediated signal transduction in colon cancer cells. AB - C-C chemokine receptor type 7 (CCR7) is involved in the development and progressions of chronic inflammatory diseases and cancer; therefore, signaling pathways that regulate CCR7 expression may represent novel molecular therapeutic targets. Previous studies by our group revealed that CCR7 is important in colon cancer progression and a is linked with cyclooxygenase (COX)-2-derived prostaglandin (PG)E2. Induction of COX-2 and membrane-associated PGE synthase 1 (mPGES-1), which are overexpressed in numerous cancer types, cooperatively enhance PGE2 expression, which contributes to carcinogenesis and cancer progression. The present study investigated whether CCR7 expression is associated with the levels of mPGES-1-derived PGE2. The results showed that mPGES-1 dependent release of PGE2 was markedly induced in colon cancer cells after transient transfection with mPGES-1 overexpression vector, accompanied by elevated CCR7 expression. PGE2 levels and CCR7 expression were markedly attenuated in colon cancer cells in which mPGES-1 was blocked, which identified mPGES-1 as a potential therapeutic target for the regulation of CCR7 expression. Finally, overexpression of CCR7 was partly mediated through the AKT/glycogen synthase kinase 3beta signaling pathway dependent on the binding of mPGES-1 derived PGE2 to the prostaglandin EP4 receptor. Thus, in addition to inhibitors of mPGES-1 expression, EP4 antagonists and AKT/GSK-3beta inhibitors may emerge as potential therapeutics to reduce CCR7 expression in colon cancer. PMID- 26352872 TI - ABCC5 and ABCG1 polymorphisms predict irinotecan-induced severe toxicity in metastatic colorectal cancer patients. AB - OBJECTIVE: Irinotecan is a cytotoxic agent used widely for the treatment of solid tumors, particularly for metastatic colorectal cancers. Treatment with this drug frequently results in severe neutropenia and diarrhea that can markedly impact the course of treatment and patients' quality of life. Pharmacogenomic tailoring of irinotecan-based chemotherapy has been the subject of several investigations, but with limited data on ATP-binding cassette (ABC) and solute carrier (SLC) transporter genes. MATERIALS AND METHODS: In this study, we aimed to discover toxicity-associated markers in seven transporter genes participating in irinotecan pharmacokinetics involving the ABC transporter genes ABCB1, ABCC1, ABCC2, ABCC5, ABCG1, and ABCG2 and the solute carrier organic anion transporter gene SLCO1B1 and using a haplotype-tagging single-nucleotide polymorphisms (n=210 htSNPs) strategy. The profiles of 167 metastatic colorectal cancer Canadian patients treated with FOLFIRI-based regimens were examined and the findings were replicated in an independent cohort of 250 Italian patients. RESULTS: In combined cohorts, a two-marker ABCC5 rs3749438 and rs10937158 haplotype (T-C) predicted lower risk of severe diarrhea [odds ratio (OR) of 0.43; P=0.001]. The co occurrence of ABCG1 rs225440T and ABCC5 rs2292997A predicted the risk of severe neutropenia (OR=5.93; P=0.0002), which was further improved when incorporating the well-known risk marker UGT1A1*28 rs8175347 (OR=7.68; P<0.0001). In contrast, carriers of one protective marker (UGT1 rs11563250G) but none of these risk alleles experienced significantly less severe neutropenia (8.2 vs. 34.0%; P<0.0001). CONCLUSION: This combination of predictive genetic markers could potentially lead to better risk assessment and may thus improve personalized treatment. PMID- 26352873 TI - 2015 Gout Classification Criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. AB - OBJECTIVE: Existing criteria for the classification of gout have suboptimal sensitivity and/or specificity, and were developed at a time when advanced imaging was not available. The current effort was undertaken to develop new classification criteria for gout. METHODS: An international group of investigators, supported by the American College of Rheumatology and the European League Against Rheumatism, conducted a systematic review of the literature on advanced imaging of gout, a diagnostic study in which the presence of monosodium urate monohydrate (MSU) crystals in synovial fluid or tophus was the gold standard, a ranking exercise of paper patient cases, and a multicriterion decision analysis exercise. These data formed the basis for developing the classification criteria, which were tested in an independent data set. RESULTS: The entry criterion for the new classification criteria requires the occurrence of at least 1 episode of peripheral joint or bursal swelling, pain, or tenderness. The presence of MSU crystals in a symptomatic joint/bursa (i.e., synovial fluid) or in a tophus is a sufficient criterion for classification of the subject as having gout, and does not require further scoring. The domains of the new classification criteria include clinical (pattern of joint/bursa involvement, characteristics and time course of symptomatic episodes), laboratory (serum urate, MSU-negative synovial fluid aspirate), and imaging (double-contour sign on ultrasound or urate on dual-energy computed tomography, radiographic gout related erosion). The sensitivity and specificity of the criteria are high (92% and 89%, respectively). CONCLUSION: The new classification criteria, developed using a data-driven and decision analytic approach, have excellent performance characteristics and incorporate current state-of-the-art evidence regarding gout. PMID- 26352875 TI - A simple model to understand the effect of membrane shear elasticity and stress free shape on the motion of red blood cells in shear flow. AB - An analytical model was proposed by Keller and Skalak in 1982 to understand the motion of red blood cells in shear flow. The cell was described as a fluid ellipsoid of fixed shape. This model was extended in 2007 to introduce shear elasticity of the red blood cell membrane. Here, this model is further extended to take into account that the cell discoid shape physiologically observed is not a stress-free shape. The model shows that spheroid stress-free shapes allow us to fit the experimental data with the values of shear elasticity typical to that found with micropipette and optical tweezer experiments. In the range of moderate shear rates (for which RBCs keep their discoid shape) this model enables us to quantitatively determine (i) an effective cell viscosity, which combines membrane and hemoglobin viscosities and (ii) an effective shear modulus of the membrane that combines the shear modulus and the stress-free shape. This model can also be used to determine RBC mechanical parameters not only in the tanktreading regime when cells are suspended in medium of high viscosity but also in the tumbling regime characteristic of cells suspended in media of low viscosity. In this regime, a transition is predicted between a rigid-like tumbling motion and a fluid-like tumbling motion above a critical shear rate, which is directly related to the mechanical parameters of the cell. PMID- 26352876 TI - Genetics of Congenital Corneal Opacification--Impact on Diagnosis and Treatment. AB - As our understanding of phenotype has improved with improving anterior segment imaging, it has become increasingly clear that the early genotype-phenotype correlations were largely misled by inaccurate phenotyping. Using a novel classification, congenital or neonatal corneal opacification can be considered to be primary or secondary. Secondary corneal disease may be developmental or acquired. Genetic analysis using this phenotypic classification becomes easier to navigate. Primary corneal disease includes endothelial dystrophies, corneal dermoids, cornea plana, and CYP1B1 cytopathy. Genotyping for all these conditions is reasonably advanced. Secondary developmental corneal disease includes entities that are the least well understood genotypically. These are kerato-irido lenticular dysgenesis (also known as Peters anomaly, types 1 and 2). The genotyping literature of these conditions is littered with confusion. Iridocorneal adhesions (Peters anomaly 1) are often avascular, whereas keratolenticular adhesions (Peters anomaly 2) are usually vascularized. Children with a known molecular diagnosis can have iridocorneal adhesion in one eye and keratolenticular adhesion in the other eye. This further supports the notion that Peters anomaly 1 or 2 is a sign and not a diagnosis. Further types of kerato irido-lenticular dysgenesis are those in which the lens fails to form or forms and then degenerates. Genotyping in these cases has been somewhat more fruitful but, as always, not comprehensive. If the lens fails to form or forms partially, the gene involved is FOXE3, which is a lens gene. Not surprisingly, if the lens forms partially or fails to form, this has an effect on the vitreous and the drainage angle. These cases are often associated with severe glaucoma. Other secondary developmental corneal diseases may include Axenfeld-Rieger syndrome, Aniridia, and primary congenital glaucoma, all of which have specific genotypic characterization. Other secondary causes are acquired and include infection, trauma, and metabolic disorders. PMID- 26352874 TI - 2015 recommendations for the management of polymyalgia rheumatica: a European League Against Rheumatism/American College of Rheumatology collaborative initiative. AB - Therapy for polymyalgia rheumatica (PMR) varies widely in clinical practice as international recommendations for PMR treatment are not currently available. In this paper, we report the 2015 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) recommendations for the management of PMR. We used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology as a framework for the project. Accordingly, the direction and strength of the recommendations are based on the quality of evidence, the balance between desirable and undesirable effects, patients' and clinicians' values and preferences, and resource use. Eight overarching principles and nine specific recommendations were developed covering several aspects of PMR, including basic and follow-up investigations of patients under treatment, risk factor assessment, medical access for patients and specialist referral, treatment strategies such as initial glucocorticoid (GC) doses and subsequent tapering regimens, use of intramuscular GCs and disease modifying anti rheumatic drugs (DMARDs), as well as the roles of non-steroidal anti-rheumatic drugs and non-pharmacological interventions. These recommendations will inform primary, secondary and tertiary care physicians about an international consensus on the management of PMR. These recommendations should serve to inform clinicians about best practices in the care of patients with PMR. PMID- 26352877 TI - Characterization of Bacterial Cellulose by Gluconacetobacter hansenii CGMCC 3917. AB - In this study, comprehensive characterization and drying methods on properties of bacterial cellulose were analyzed. Bacterial cellulose was prepared by Gluconacetobacter hansenii CGMCC 3917, which was mutated by high hydrostatic pressure (HHP) treatment. Bacterial cellulose is mainly comprised of cellulose Ialpha with high crystallinity and purity. High-water holding and absorption capacity were examined by reticulated structure. Thermogravimetric analysis showed high thermal stability. High tensile strength and Young's modulus indicated its mechanical properties. The rheological analysis showed that bacterial cellulose had good consistency and viscosity. These results indicated that bacterial cellulose is a potential food additive and also could be used for a food packaging material. The high textural stability during freeze-thaw cycles makes bacterial cellulose an effective additive for frozen food products. In addition, the properties of bacterial cellulose can be affected by drying methods. Our results suggest that the bacterial cellulose produced from HHP mutant strain has an effective characterization, which can be used for a wide range of applications in food industry. PMID- 26352878 TI - Analysis of the differential secretome of nasopharyngeal carcinoma cell lines CNE 2R and CNE-2. AB - Radioresistance is the major cause of poor prognosis in nasopharyngeal carcinoma (NPC). To identify and characterize the secretome associated with NPC radioresistance, we compared the conditioned serum-free medium of radioresistant CNE-2R cells with that of the parental radiosensitive CNE-2 cells using isobaric tags for relative and absolute quantitation (iTRAQ) with liquid chromatography electrospray tandem mass spectrometry (LC-ESI-MS/MS) quantitative proteomics. Before proceeding to quantitative proteomics, we investigated the survival curves of CNE-2R and CNE-2 cells by colony formation assay, and the CNE-2R survival curves were significantly higher than those for CNE-2. In total, 3,581 proteins were identified in the quantitative proteomics experiments, and 40 proteins exhibited significant differences between the CNE-2R and CNE-2 cells. Twenty-six of the 40 proteins were secreted by classical, non-classical, or exosomal secretion pathways. To verify the reliability of iTRAQ quantitative proteomics, we applied western blotting (WB) to study the secretory protein expression of fibrillin-2, CD166, sulfhydryl oxidase 1 and cofilin-2, which are involved in cell adhesion, migration and invasion. The WB results showed that fibrillin-2 (p=0.017) and sulfhydryl oxidase 1 (p=0.000) were highly expressed in the CNE-2 cells, while CD166 (p=0.012) and cofilin-2 (p=0.003) were highly expressed in the CNE-2R cells, which was in accordance with iTRAQ quantitative proteomics. Finally, a phenotypic subset of CD166-positive NPC cells was verified by immunocytochemistry. In summary, we defined a collection of secretory proteins that may be relevant to the radioresistance in NPC cells, and we determined that CD166, which is widely used as a positive marker of cancer stem cells, is expressed in NPC cells. PMID- 26352879 TI - Impact of genetic polymorphisms associated with nonalcoholic fatty liver disease on HIV-infected individuals. AB - OBJECTIVE: Fatty liver disease (FLD) is frequently observed in HIV-infected patients and a cause of advanced liver disease. Genetic factors could play a role in determining risk for FLD development in those patients. The aim of this study was to evaluate the association of those single nucleotide polymorphisms (SNPs) previously found to be related to nonalcoholic FLD by genome-wide association analyses in the general population with the presence of FLD, including steatohepatitis, in HIV-infected individuals. DESIGN: This is a transversal study. METHODS: A total of 431 HIV-infected patients were included in this study. All of them underwent a transient elastography with the controlled attenuation parameter examination and were genotyped for 19 selected SNPs. A controlled attenuation parameter value higher than 238 dB/m was selected to define the presence of FLD. Elevated alanine aminotransferase levels and presence of FLD was considered as a surrogate marker of steatohepatitis. RESULTS: A total of 179 (41.5%) individuals showed FLD, including 122 (28.3%) with steatohepatitis. The rs12743824 and rs738491 SNPs were independently associated with FLD and steatohepatitis, respectively. For rs12743824, among 252 individuals without FLD, 182 (72.2%) were A-allele carriers vs. 111 (62%) of 179 patients with this disease (multivariate P = 0.006; adjusted odds ratio = 0.51; 95% confidence interval = 0.33-0.83). For rs738491, 20 (16.4%) of 122 patients with steatohepatitis were TT carriers vs. 18 (5.8%) of 309 patients without this condition (multivariate P = 0.005; adjusted odds ratio = 2.94; 95% confidence interval = 1.39-6.20). CONCLUSION: LPPR4 and SAMM50 allelic variants are independent risk factors for FLD and steatohepatitis development, respectively, in HIV-infected individuals. PMID- 26352881 TI - Understanding risk factors for incident maternal HIV-1 infection. PMID- 26352880 TI - HIV acquisition during pregnancy and postpartum is associated with genital infections and partnership characteristics. AB - OBJECTIVE: The objective of this study is to determine the risk and cofactors for HIV acquisition during pregnancy and postpartum. DESIGN: A prospective cohort study METHODS: : Pregnant women in western Kenya were enrolled if HIV seronegative at that visit or within 3 months. Serial HIV nucleic acid amplification tests (NAATs) were conducted at 1 to 3-month intervals to 9 months postpartum. Genital swabs were collected for detection of chlamydia and gonorrhoea at baseline, and for trichomonas, bacterial vaginosis and yeast at baseline and follow-up. RESULTS: Among 1304 pregnant women, median age was 22 years, 78% were married for a median of 4 years, 66% reported knowing partner HIV status and 8% reported using condoms. Study retention was 98%. During 1235 person years of follow-up, HIV incidence was 2.31/100 person-years [95% confidence interval (95% CI) 0.71-4.10]. Incident HIV was associated with syphilis (hazard ratio 9.18, 95% CI 2.15-39.3), chlamydia (hazard ratio 4.49, 95% CI 1.34-15.0), bacterial vaginosis (hazard ratio 2.91, 95% CI 1.25-6.76), yeast (hazard ratio 3.46, 95% CI 1.46-8.19), sexually transmitted infection (STI) history (hazard ratio 3.48, 95% CI 1.31-9.27), lifetime number of sex partners (hazard ratio 1.19, 95% CI 1.03-1.37), partner age discordance (hazard ratio 1.07 per year, 95% CI 1.02-1.13) and shorter marriage (hazard ratio 1.19 per year, 95% CI 1.03 1.38). No women with incident HIV reported an HIV-infected partner. In multivariate analyses, chlamydia, older partners and yeast infection remained significant; however, power was limited. CONCLUSION: Pregnant and lactating women may not perceive HIV risk and rarely used condoms. Prevention and treatment of genital infections and risk stratification to identify women for pre-exposure prophylaxis (PrEP) could decrease HIV acquisition in pregnant/lactating women. PMID- 26352882 TI - High completion of isoniazid preventive therapy among HIV-infected children and adults in Kinshasa, Democratic Republic of Congo. AB - We assessed isoniazid preventive therapy (IPT) completion and predictors among HIV-infected children and adults in two HIV clinics in Kinshasa, Democratic Republic of Congo. Between 1 September 2012 and 15 June 2013, 546 children (1-15 years) and 1532 adults (>15 years) were initiated on IPT; 86.6% (408/470) of the children and 88.2% (1129/1280) of the adults with an IPT outcome completed their therapy. Patients on antiretroviral therapy at IPT initiation were more likely to complete IPT. PMID- 26352883 TI - Decrease of renal function in HCV and HIV/HCV-infected patients with telaprevir based therapy. PMID- 26352884 TI - A history of infection with varicella is strongly predictive of the presence of varicella-zoster virus antibodies in a heterogenous Australian HIV cohort. PMID- 26352885 TI - Centerband-only-detection-of-exchange (31)P nuclear magnetic resonance and phospholipid lateral diffusion: theory, simulation and experiment. AB - Centerband-only-detection-of-exchange (CODEX) (31)P NMR lateral diffusion measurements were performed on dimyristoylphosphatidylcholine (DMPC) assembled into large unilamellar spherical vesicles. Optimization of sample and NMR acquisition conditions provided significant sensitivity enhancements relative to an earlier first report (Q. Saleem, A. Lai, H. Morales, and P. M. Macdonald, Chem. Phys. Lipids, 2012, 165, 721). An analytical description was developed that permitted the extraction of lateral diffusion coefficients from CODEX data, based on a Gaussian-diffusion-on-a-sphere model (A. Ghosh, J. Samuel, and S. Sinha, Europhys. Lett., 2012, 98, 30003-p1) as relevant to CODEX (31)P NMR measurements on a population of spherical unilamellar phospholipid bilayer vesicles displaying a distribution of vesicle radii. PMID- 26352886 TI - The "ASC(ST)O" meeting. PMID- 26352888 TI - Intermittent dosing in melanoma. PMID- 26352889 TI - MET as a drug target. PMID- 26352890 TI - New therapies for polycythemia vera. PMID- 26352891 TI - Imaging techniques for hepatocellular carcinoma. PMID- 26352892 TI - The future of kidney cancer treatment. PMID- 26352893 TI - Immunology and breast cancer: toward a new way of understanding breast cancer and developing novel therapeutic strategies. AB - Every cancer triggers an immune response that constitutes an important first-line protection against cancer progression. In breast cancer, there is an increasing awareness of the relationship between the immune system and tumor evolution. The tumor microenvironment is composed of a variety of immune cells that can control or arrest malignant progression. Chemotherapy and targeted therapy have been shown to modulate this immune microenvironment. Recently, tumor-infiltrating lymphocytes have emerged as a predictive and prognostic biomarker in early breast cancer. In addition, immune gene expression signatures have been shown to be associated with prognosis in triple-negative and human epidermal growth factor receptor 2-positive breast cancer. Such findings have increased interest in the development of immunotherapeutic agents for breast cancer, and multiple clinical trials of anticancer vaccines and immune checkpoint inhibitors are ongoing. In this review, we summarize what is known about the relationship between immunity and breast carcinoma, explore the relevance of this information to the clinical and research settings, and give a portrait of new therapeutic strategies using immunotherapy in breast cancer. PMID- 26352894 TI - Non-clear cell renal cell carcinoma, part 2: therapy. AB - Non-clear cell renal cell carcinomas (RCCs) represent a heterogeneous group of diseases with distinct molecular drivers, histologies, and clinical outcomes. Their low incidence and heterogeneity have resulted in a lack of studies that address the optimal strategies for each subtype. This article (the second in a 2 part series) reviews the current targeted therapies approved for RCC, such as the vascular endothelial growth factor receptor tyrosine kinase inhibitors and the mammalian target of rapamycin inhibitors. Ongoing studies will provide more information regarding the role of these agents in non-clear cell RCC. Ultimately, enhanced understanding of genetic triggers and the development of more tailored treatments remain imperative to improve outcomes in non-clear cell RCC. PMID- 26352895 TI - Renal cell carcinoma in patients with a personal or family history of hematologic malignancies. AB - A little-appreciated association between renal cell carcinoma (RCC) and hematologic malignancies (HMs) has been reported for at least 20 years. The HM characteristically occurs first in patients with both neoplasms, and the large majority (94%) of these HMs are of B-cell origin. Furthermore, the majority of patients with RCC and an HM are male. Recently, we have noted an increased incidence of HMs in families of patients with RCC and are exploring this observation further. Here, we summarize our reports on the association between these neoplasms in individual patients and review the relevant literature. PMID- 26352896 TI - Metallic Limus-Eluting Stents Abluminally Coated with Biodegradable Polymers: Angiographic and Clinical Comparison of a Novel Ultra-Thin Sirolimus Stent Versus Biolimus Stent in the DESTINY Randomized Trial. AB - AIMS: To evaluate the outcomes of patients treated with a new drug-eluting stent formulation with low doses of sirolimus, built in an ultra-thin-strut platform coated with biodegradable abluminal coating. METHODS: This study is a randomized trial that tested the main hypothesis that the angiographic late lumen loss of the novel sirolimus-eluting stent is noninferior compared with commercially available biolimus-eluting stent. A final study population comprising 170 patients with one or two de novo lesions was randomized in the ratio 2:1 for sirolimus-eluting stent or biolimus-eluting stent, respectively. The primary endpoint was 9-month angiographic in-stent late lumen loss. Adverse clinical events were prospectively collected for 1 year. RESULTS: After 9 months, the novel sirolimus-eluting stent was shown noninferior compared with the biolimus stent for the primary endpoint (angiographic in-stent late lumen loss: 0.20 +/- 0.29 mm vs. 0.15 +/- 0.20 mm, respectively; P value for noninferiority <0.001). The 1-year incidence of death, myocardial infarction, repeat revascularization, and stent thrombosis remained low and not significantly different between the groups. CONCLUSIONS: The present randomized trial demonstrates that the tested novel sirolimus-eluting stent was angiographically noninferior in comparison with a last-generation biolimus-eluting stent. PMID- 26352897 TI - Analytical Profiling of Bioactive Phenolic Compounds in Argan (Argania spinosa) Leaves by Combined Microextraction by Packed Sorbent (MEPS) and LC-DAD-MS/MS. AB - INTRODUCTION: The argan tree (Argania spinosa) is an endemic species from south western Morocco. Argan-based preparations have been widely used in Moroccan traditional medicine for their biological properties, as well as for several cosmetic purposes. Whereas kernel, pulp of fruit and trunk have been extensively studied for their nutritional and pharmacological effects, relatively little is known about argan tree leaves. OBJECTIVE: The main purpose of the present study is to investigate and characterise the bioactive phenolic fractions in both crude and aqueous extracts derived from argan tree leaves. METHODOLOGY: A qualitative profile of the antioxidant phenolic compounds in argan leaves was obtained by means of structural hypothesis based on UV spectra and mass spectrometric fragmentation patterns. Moreover, selected phenolics were quantified in argan leaves by using a fully validated method based on liquid chromatography coupled to diode array detection and tandem mass spectrometry (LC-DAD-MS/MS). All the extracts were purified by a fast and reliable microextraction by packed sorbent (MEPS) procedure, before analysing them by LC-MS/MS. RESULTS: Based on retention times, mass spectrometric fragmentation and UV spectra, 13 phenolic compounds were identified or tentatively elucidated from crude and aqueous extracts derived from Argania spinosa leaves, while seven compounds were quantified in both extracts. CONCLUSION: The obtained results could represent a first step towards a complete characterisation of the argan plant, its bioactive profiling and the valorisation of its by-products as a source of potentially beneficial bioactive molecules. PMID- 26352899 TI - How Anion Chaotrope Changes the Local Structure of Water: Insights from Photoelectron Spectroscopy and Theoretical Modeling of SCN(-) Water Clusters. AB - The behavior of charged solute molecules in aqueous solutions is often classified using the concept of kosmotropes ("structure makers") and chaotropes ("structure breakers"). There is a growing consensus that the key to kosmotropic/chaotropic behaviors lies in the local solvent region, but the exact microscopic basis for such differentiation is not well-understood. This issue is examined in this work by analyzing size selective solvation of a well-known chaotrope, a negatively charged SCN(-) molecule. Combining experimental photoelectron spectroscopy measurements with theoretical modeling, we examine evolution of solvation structure up to eight waters. We observe that SCN(-) indeed fits the description of weakly hydrated ion, and its solvation is heavily driven by stabilization of water-water interaction network. However, the impact on water structure is more subtle than that associated with "structure breaker". In particular, we observe that the solvation structure of SCN(-) preserves the "packing" structure of the water network but changes local directionality of hydrogen bonds in the local solvent region. The resulting effect is closer to that of "structure weakener", where solute can be readily accommodated into the native water network, at the cost of compromising its stability due to constraints on hydrogen bonding directionality. PMID- 26352898 TI - Enhanced Production of Androst-1,4-Diene-3,17-Dione by Mycobacterium neoaurum JC 12 Using Three-Stage Fermentation Strategy. AB - To improve the androst-1,4-diene-3,17-dione (ADD) production from phytosterol by Mycobacterium neoaurum JC-12, fructose was firstly found favorable as the initial carbon source to increase the biomass and eliminate the lag phase of M. neoaurum JC-12 in the phytosterol transformation process. Based on this phenomenon, two stage fermentation by using fructose as the initial carbon source and feeding glucose to maintain strain metabolism was designed. By applying this strategy, the fermentation duration was decreased from 168 h to 120 h with the ADD productivity increased from 0.071 g/(L.h) to 0.108 g/(L.h). Further, three-stage fermentation by adding phytosterol to improve ADD production at the end of the two-stage fermentation was carried out and the final ADD production reached 18.6 g/L, which is the highest reported ADD production using phytosterol as substrate. Thus, this strategy provides a possible way in enhancing the ADD production in pharmaceutical industry. PMID- 26352900 TI - Low temperature induces cryoinjury in mouse corneal endothelial cells by stimulating the Stk11-p53 signal pathway. AB - Cryoinjury, or injury caused by extremely low temperatures, can occur in corneal endothelial cells (CECs) and lead to visual impairment. However, the mechanism of cryoinjury in CECs is not clear. The Stk11-p53 signaling pathway regulates the proliferation and division of cells. Activity of the Stk11-p53 signaling pathway arrests the cell cycle at the G0/G1 phase and induces apoptosis. In this study, a mouse model of cryoinjury in CECs was used. Following injury, significant mouse CEC death and shedding were observed. In addition, the mRNA and protein levels of core factors from the Stk11-p53 signaling pathway (Stk11, p21 and p53) were elevated and Caspase-3 was activated following cryoinjury. In addition, chromatin immunoprecipitation revealed that Stk11 catalyzed p53 serine 15 phosphorylation, and the Stk11-p53 complex bound to the p21 promoter and stimulated gene transcription. Thus, the results of the present study suggest that cryoinjury leads to the damage and apoptosis of mouse CECs by activation of the Stk11-p53 signaling pathway, phosphorylation of p53 serine 15 and p21 gene transcription. PMID- 26352901 TI - Texture recognition and localization in amorphous robotic skin. AB - We present a soft robotic skin that can recognize and localize texture using a distributed set of sensors and computational elements that are inspired by the Pacinian corpuscle, the fast adapting, uniformly spaced mechanoreceptor with a wide receptive field, which is responsive to vibrations due to rubbing or slip on the skin. Tactile sensing and texture recognition is important for controlled manipulation of objects and navigating in one's environment. Yet, providing robotic systems or prosthetic devices with such capability at high density and bandwidth remains challenging. Each sensor node in the presented skin is created by collocating computational elements with individual microphones. These nodes are networked in a lattice and embedded in EcoFlex rubber, forming an amorphous medium. Unlike existing skins consisting of passive sensor arrays that feed into a central computer, our approach allows for detecting, conditioning and processing of tactile signals in-skin, facilitating the use of high-bandwidth signals, such as vibration, and allowing nodes to respond only to signals of interest. Communication between nodes allows the skin to localize the source of a stimulus, such as rubbing or slip, in a decentralized manner. Signal processing by individual nodes allows the skin to estimate the material touched. Combining these two capabilities, the skin is able to convert high-bandwidth, spatiotemporal information into low-bandwidth, event-driven information. Unlike taxel-based sensing arrays, this amorphous approach greatly reduces the computational load on the central robotic system. We describe the design, analysis, construction, instrumentation and programming of the robotic skin. We demonstrate that a 2.8 square meter skin with 10 sensing nodes is capable of localizing stimulus to within 2 centimeters, and that an individual sensing node can identify 15 textures with an accuracy of 71%. Finally, we discuss how such a skin could be used for full-body sensing in existing robots, augment existing sensing modalities, and how this material may be useful in robotic grasping tasks. PMID- 26352902 TI - The Classification of Biomarkers. PMID- 26352903 TI - Medical decision support systems and therapeutics: The role of autopilots. AB - For decades, medical practice has increasingly relied on prescription medicines to treat, cure, or prevent illness but their net benefit is reduced by prescribing errors that result in adverse drug reactions (ADRs) and tens of thousands of deaths each year. Optimal prescribing requires effective management of massive amounts of data. Clinical decision support systems (CDSS) can help manage information and support optimal therapeutic decisions before errors are made by operating as the prescribers' "autopilot." PMID- 26352904 TI - Long term sustained therapeutic effects of percutaneous posterior tibial nerve stimulation treatment of neurogenic overactive bladder in multiple sclerosis patients: 12-months results. AB - AIMS: The aim of this study is to determine the sustained therapeutic efficacy and treatment intervals for PTNS in NOAB with MS, offering periodic additional treatments during 1 year in patients who completed an initial course of 12 consecutive weekly sessions. METHODS: A total of 34 patients enrolled to the PTNS treatment and 21 patients completed the 1 year PTNS treatment with a tapering protocol of 6, 9, and 12 months of therapy, respectively. After 12 weeks of therapy, PTNS was applied at 14 day intervals for 3 months, 21 day intervals for 3 months, and 28 day intervals for 3 months. The patients completed a 3-day voiding diary at 3rd, 6th, 9th, and 12th month. The patients requested to complete validated questionnaires (ICIQ-SF, OAB-V8, OAB-q SF) were carried out within 3-month intervals thereafter during their enrolment in the study. RESULTS: A total of 21 patients were enrolled in the study. Of these 5 (23.8%) were men and 16 (76.2%) women. The improvements for all voiding diary parameters were significant in the 6th, 9th, and 12th months when compared with baseline. Mean values between baseline and 12 month parameters suggested that daytime frequency decreased by 5.4 voids daily, urge incontinence decreased by 3.4 episodes daily, urgency episodes decreased by 7.4 episodes daily, nocturia decreased by 2.6 voids, and voided volume improved by a mean of 72.1 cc. CONCLUSION: These results have demonstrated NOAB symptom improvement in MS patients can be achieved with 12 weekly PTNS treatments which show excellent durability over 12 months. Neurourol. Urodynam. 36:104-110, 2017. (c) 2015 Wiley Periodicals, Inc. PMID- 26352906 TI - Bioconcentration and Aquatic Toxicity of Superhydrophobic Chemicals: A Modeling Case Study of Cyclic Volatile Methyl Siloxanes. AB - Many chemicals in commerce are classified as "superhydrophobic", having log octanol-water partition coefficients (log KOW) approaching or exceeding 7. Examples include long-chain alkanes, halogenated aromatics, and cyclic volatile methylsiloxanes (cVMS). We show that superhydrophobic chemicals present unique assessment challenges because of their sparing solubility in water and difficulties in empirical determinations of bioconcentration factors (BCFs) and aquatic toxicity. Using cVMS as an example, BCFs are considerably lower than expected due to biotransformation. Reviewed aquatic toxicity test data for cVMS in a range of aquatic organisms show little or no toxic effects up to solubility limits in water and sediment. Explanations for this apparent lack of toxicity of cVMS, and by extension to other superhydrophobic chemicals, are explored using a conventional one-compartment uptake model to simulate bioconcentration and toxicity tests using an assumed baseline narcotic critical body residue (CBR) and a range of organism sizes. Because of the low aqueous concentrations, equilibration times are very long and BCFs are sensitive to even very slow rates of biotransformation. Most organisms fail to achieve the assumed CBR during feasible test durations even at the solubility limit. Regulatory evaluation of superhydrophobic substances requires specially designed test protocols addressing biotransformation and dietary uptake. PMID- 26352908 TI - Mapping and Quantifying Surface Charges on Clay Nanoparticles. AB - Understanding the electrical properties of clay nanoparticles is very important since they play a crucial role in every aspect of oil sands processing, from bitumen extraction to sedimentation in mature fine tailings (MFT). Here, we report the direct mapping and quantification of surface charges on clay nanoparticles using Kelvin probe force microscopy (KPFM) and electrostatic force microscopy (EFM). The morphology of clean kaolinite clay nanoparticles shows a layered structure, while the corresponding surface potential map shows a layer dependent charge distribution. More importantly, a surface charge density of 25 nC/cm(2) was estimated for clean kaolinite layers by using EFM measurements. On the other hand, the EFM measurements show that the clay particles obtained from the tailings demonstrate a reduced surface charge density of 7 nC/cm(2), which may be possibly attributed to the presence of various bituminous compounds residing on the clay surfaces. PMID- 26352907 TI - New mouse xenograft model modulated by tumor-associated fibroblasts for human multi-drug resistance in cancer. AB - We developed an MDR tumor model that is modulated by tumor-associated fibroblasts. Studies on proliferation of tumor cell lines including paclitaxel sensitive and resistant cell lines were performed. The expressions of P-gp and alpha-smooth muscle actin (alpha-SMA) antigen were evaluated by immunohistochemistry and western blot analysis. Quantitative P-gp analyses of different cell lines were accomplished by nanoUPLC-MS/MS. Tumor cell colony formation assay and established xenograft model was used to investigate the relationship between P-gp expression, fibroblast levels and tumorigenesis. The mouse xenograft model was developed after co-inoculation with MDR tumor cells and NIH/3T3 fibroblast cells. There was no correlation between tumorigenesis in vivo and the growth rate of cells in vitro. The proliferation among different cell lines had no significant differences, but the P-gp expression and tumor growth in the xenograft model were fairly different. P-gp determination and alpha-SMA immunofluorescence staining clarified the relationship between P-gp expression, fibroblast levels and tumorigenesis. It was more difficult for tumor cells with higher P-gp levels to recruit fibroblasts in vivo, resulting in lower tumorigenesis due to the lack of structural and chemical support during tumor progression. In the established paclitaxel-resistant mouse xenograft model, no obvious antitumor effect was observed after Taxol treatment, but a significant decrease in tumor size for the group treated with gemcitabine sensitive to the model. The results show that the added fibroblasts do not disturb the applicability of the model in MDR. Therefore, this mouse xenograft MDR model could serve as an effective tool for MDR research. PMID- 26352909 TI - Update in hospital medicine: Evidence you should know. AB - BACKGROUND: The practice of hospital medicine is complex, and the number of clinical publications each year continues to grow. To maintain best practice it is necessary for hospitalists to stay abreast of the literature, but difficult to accomplish due to time. The annual Society of Hospital Medicine meeting offers a plenary session on Updates in Hospital Medicine. This article is a summary of those papers presented at the meeting. METHODS: We reviewed articles published between January 2014 and January 2015 in the leading medical journals, searching for papers with good methodological quality, the potential to change practice, and papers that are thought provoking. The authors collectively agreed on 14 articles. The findings, cautions, and implications are discussed for each paper. RESULTS: Key findings include: a novel neprilysin inhibitor and angiotensin receptor blocker combination drug reduces mortality in patients with heart failure; the concern for acute kidney injury after venous contrast may be overstated; the Confusion Assessment Method Severity score is an important tool for prognostication in delirious patients; ramelteon shows promise for lowering incident delirium among elderly medical patients; polyethylene glycol appears effective in rapidly resolving hepatic encephalopathy; cirrhotic patients on a nonselective beta-blocker have increased mortality after they develop spontaneous bacterial peritonitis; current guidelines regarding prophylaxis against venous thromboembolism (VTE) in medical inpatients likely result in non-beneficial use of medications; from a safety and efficacy perspective, direct oral anticoagulants perform quite well against conventional therapies in patients with VTE and atrial fibrillation, including in elderly populations; 2 new once-weekly antibiotics, dalbavancin and oritivancin, approved for skin and soft tissue infections, appear noninferior to vancomycin; offering family members of a patient undergoing cardiopulmonary resuscitation the opportunity to observe has durable impact on long-term psychological outcomes. CONCLUSIONS: This update reviews key clinical articles published in 2014, selected by the authors for their methodological quality and potential for changing the practice of inpatient physicians. All of these articles add to the body of inpatient medical knowledge and contribute to the debate on best practices. PMID- 26352910 TI - Micro RNAs mir-106a, mir-122 and mir-197 are increased in severe acute viral hepatitis with coagulopathy. AB - BACKGROUND & AIMS: The severity of acute viral hepatitis, which may be caused by several distinct viruses, varies among individual patients. In rare cases, severe hepatic injury with sudden loss of liver function may occur, which is clinically indicated by the occurrence of coagulopathy or encephalopathy. As the molecular mechanisms of this liver injury are largely unknown, we investigated extracellular micro RNA (miRNA) profiles in 54 patients acutely infected with one of four different hepatotropic viruses, in order to identify those miRNAs which indicate severe viral hepatitis associated with coagulopathy. METHODS: First, the profile of miRNAs was extensively analysed using a microarray-based approach in highly characterized 24 patients, matched in terms of sex, age and level of liver enzymes, as well as in three healthy controls. The cohort included samples from 18 patients with moderate and six individuals with severe hepatitis, indicated by abnormal prothrombin time and higher alanine aminotransferase and bilirubin levels. miRNAs found to be upregulated in severe hepatitis were then quantified by real-time PCR in the expanded cohort of 54 patients. RESULTS: Comprehensive microarray-based miRNA profiling identified upregulation of mir-106a, mir-122 and mir-197 in patients with severe acute viral hepatitis with coagulopathy, as compared to patients who did not develop coagulopathy. mir-106a, mir-122 and mir 197 were then proven to be significantly upregulated in patients with severe acute viral hepatitis by quantitative real-time PCR (P < 0.01, Mann-Whitney U test). CONCLUSIONS: mir-106a, mir-122 and mir-197 could be potential markers for severe acute viral hepatitis associated with coagulopathy. PMID- 26352912 TI - Multiparametric Quantitation of the Bacillus cereus Toxins Cereulide and Isocereulides A-G in Foods. AB - Consumption of food products contaminated with cereulide (1), a toxin produced by Bacillus cereus, might cause intoxications with symptoms reported to range from indigestion pain and emesis to death. Recently, a series of structural variants, coined isocereulides A-G (2-8), were identified for the first time to be produced along with cereulide (1). The observation that isocereulide A (2) shows an ~ 8 fold increased cytotoxicity when compared to 1 urges the development of analytical tools enabling an accurate quantitation of these toxins. Therefore, a rapid, sensitive, and robust stable isotope dilution assay (SIDA) was developed for the combined quantitation of 1-8 by means of UPLC-MS/MS. On average, trueness and precision of the method were 112.5 +/- 1.8% RSD, repeatability and reproducibility were 2 and 4% for cereulide and isocereulides A-G, and the LOD and LOQ of 0.1 and 0.5 ng/g, respectively, demonstrated a high sensitivity for the developed SIDA method. Application of this method to food samples revealed elevated levels of 1-8 in two suspicious noodle samples, for example, ranging from 0.59 (7) to 189.08 ng/g (1) in sample 1 and from 5.77 (7) to 6198.17 ng/g (1) in sample 2, whereas the analysis of 25 randomly selected food samples, which have not been the subject to any complaints, did not contain detectable amounts of any of these toxins. As a consequence, this SIDA method could add an important contribution to the knowledge-based risk assessment of B. cereus toxins in foods. PMID- 26352911 TI - Understanding the Impact of Brain Disorders: Towards a 'Horizontal Epidemiology' of Psychosocial Difficulties and Their Determinants. AB - OBJECTIVE: To test the hypothesis of 'horizontal epidemiology', i.e. that psychosocial difficulties (PSDs), such as sleep disturbances, emotional instability and difficulties in personal interactions, and their environmental determinants are experienced in common across neurological and psychiatric disorders, together called brain disorders. STUDY DESIGN: A multi-method study involving systematic literature reviews, content analysis of patient-reported outcomes and outcome instruments, clinical input and a qualitative study was carried out to generate a pool of PSD and environmental determinants relevant for nine different brain disorders, namely epilepsy, migraine, multiple sclerosis, Parkinson's disease, stroke, dementia, depression, schizophrenia and substance dependency. Information from these sources was harmonized and compiled, and after feedback from external experts, a data collection protocol including PSD and determinants common across these nine disorders was developed. This protocol was implemented as an interview in a cross-sectional study including a convenience sample of persons with one of the nine brain disorders. PSDs endorsed by at least 25% of patients with a brain disorder were considered associated with the disorder. PSD were considered common across disorders if associated to 5 out of the 9 brain disorders and if among the 5 both neurological and psychiatric conditions were represented. SETTING: The data collection protocol with 64 PSDs and 20 determinants was used to collect data from a convenience sample of 722 persons in four specialized health care facilities in Europe. RESULTS: 57 of the PSDs and 16 of the determinants included in the protocol were found to be experienced across brain disorders. CONCLUSION: This is the first evidence that supports the hypothesis of horizontal epidemiology in brain disorders. This result challenges the brain disorder-specific or vertical approach in which clinical and epidemiological research about psychosocial difficulties experienced in daily life is commonly carried in neurology and psychiatry and the way in which the corresponding health care delivery is practiced in many countries of the world. PMID- 26352913 TI - Terminal Differentiation of CD56(dim)CD16(+) Natural Killer Cells Is Associated with Increase in Natural Killer Cell Frequencies After Antiretroviral Treatment in HIV-1 Infection. AB - HIV-1 infection results in immunological abnormalities of natural killer (NK) cells such as disturbed distribution of NK cell subsets and downmodulation of activating and upregulation of inhibitory receptors thereby diminishing NK cell killing capacity and cytokine secretion. Antiretroviral treatment (ART) is known to restore phenotype and functions of NK cells. However, the effects of ART on NK cell terminal differentiation, activation, and disturbed distribution have not been studied yet longitudinally. Here, we analyzed the effects of ART on these parameters of peripheral blood NK cells in a longitudinal as well as in a cross sectional study. We observed that expanded CD56(-)CD16(+) NK cell frequency is inversely correlated with the frequency of CD56(dim)CD16(+) NK cells in treatment naive HIV-1 patients. Loss of CD56(dim)CD16(+) and expansion of CD56(-)CD16(+) NK cells again restore to the levels of healthy controls after ART. Enhanced immune activation of different NK cell subsets is partially restored after ART. Terminal differentiation of CD56(dim)CD16(+) NK cells is enhanced after ART as measured by CD57 expression. Frequencies of CD57(+)CD56(dim)CD16(+) NK cells are directly correlated with the frequencies of total NK cells suggesting that an increase in the frequencies of CD57(+)CD56(dim)CD16(+) NK cells is reflected by increased frequencies of total NK cells after ART. Taken together these data demonstrate that ART has an effect on the immune restoration of NK cells and is enhanced in the terminal differentiation of CD56(dim)CD16(+) NK cells, which is associated with increased frequencies of total NK cells after ART. PMID- 26352914 TI - Visualizing peroxynitrite fluxes in endothelial cells reveals the dynamic progression of brain vascular injury. AB - Accumulating evidence suggests that formation of peroxynitrite (ONOO(-)) in the cerebral vasculature contributes to the progression of ischemic damage, while the underlying molecular mechanisms remain elusive. To fully understand ONOO(-) biology, efficient tools that can realize the real-time tracing of endogenous ONOO(-) fluxes are indispensable. While a few ONOO(-) fluorescent probes have been reported, direct visualization of ONOO(-) fluxes in the cerebral vasculature of live mice remains a challenge. Herein, we present a fluorescent switch-on probe (NP3) for ONOO(-) imaging. NP3 exhibits good specificity, fast response, and high sensitivity toward ONOO(-) both in vitro and in vivo. Moreover, NP3 is two-photon excitable and readily blood-brain barrier penetrable. These desired photophysical and pharmacokinetic properties endow NP3 with the capability to monitor brain vascular ONOO(-) generation after injury with excellent temporal and spatial resolution. As a proof of concept, NP3 has enabled the direct visualization of neurovascular ONOO(-) formation in ischemia progression in live mouse brain by use of two-photon laser scanning microscopy. Due to these favorable properties, NP3 holds great promise for visualizing endogenous peroxynitrite fluxes in a variety of pathophysiological progressions in vitro and in vivo. PMID- 26352915 TI - Chemical Dynamic Thermodynamic Resolution and S/R Interconversion of Unprotected Unnatural Tailor-made alpha-Amino Acids. AB - Described here is an advanced, general method for purely chemical dynamic thermodynamic resolution and S/R interconversion of unprotected tailor-made alpha amino acids (alpha-AAs) through intermediate formation of the corresponding nickel(II)-chelated Schiff bases. The method features virtually complete stereochemical outcome, broad substrate generality (35 examples), and operationally convenient conditions allowing for large-scale preparation of the target alpha-AAs in enantiomerically pure form. Furthermore, the new type of nonracemizable axially chiral ligands can be quantitatively recycled and reused, rendering the whole process economically and synthetically attractive. PMID- 26352917 TI - Methodology for Knowledge Synthesis of the Management of Vaccination Pain and Needle Fear. AB - BACKGROUND: A knowledge synthesis was undertaken to inform the development of a revised and expanded clinical practice guideline about managing vaccination pain in children to include the management of pain across the lifespan and the management of fear in individuals with high levels of needle fear. This manuscript describes the methodological details of the knowledge synthesis and presents the list of included clinical questions, critical and important outcomes, search strategy, and search strategy results. METHODS: The Grading of Assessments, Recommendations, Development and Evaluation (GRADE) and Cochrane methodologies provided the general framework. The project team voted on clinical questions for inclusion and critically important and important outcomes. A broad search strategy was used to identify relevant randomized-controlled trials and quasi-randomized-controlled trials. Quality of research evidence was assessed using the Cochrane risk of bias tool and quality across studies was assessed using GRADE. Multiple measures of the same construct within studies (eg, observer rated and parent-rated infant distress) were combined before pooling. The standardized mean difference and 95% confidence intervals (CI) or relative risk and 95% CI was used to express the effects of an intervention. RESULTS: Altogether, 55 clinical questions were selected for inclusion in the knowledge synthesis; 49 pertained to pain management during vaccine injections and 6 pertained to fear management in individuals with high levels of needle fear. Pain, fear, and distress were typically prioritized as critically important outcomes across clinical questions. The search strategy identified 136 relevant studies. CONCLUSIONS: This manuscript describes the methodological details of a knowledge synthesis about pain management during vaccination and fear management in individuals with high levels of needle fear. Subsequent manuscripts in this series will present the results for the included questions. PMID- 26352918 TI - HELPinKids&Adults Knowledge Synthesis of the Management of Vaccination Pain and High Levels of Needle Fear: Limitations of the Evidence and Recommendations for Future Research. AB - The HELPinKids&Adults knowledge synthesis for the management of vaccination related pain and high levels of needle fear updated and expanded upon the 2010 HELPinKIDS knowledge synthesis and clinical practice guideline for pain mitigation during vaccine injections in childhood. Interventions for vaccine pain management in adults and treatment of individuals with high levels of needle fear, phobias, or both were included, thereby broadening the reach of this work. The present paper outlines the overarching limitations of this diverse evidence base and provides recommendations for future research. Consistent with the framing of clinical questions in the systematic reviews, the Participants, Intervention, Comparison, Outcome, Study design (PICOAS) framework was used to organize these predominant issues and research directions. The major limitations we identified across systematic reviews were an overall dearth of trials on vaccination, lack of methodological rigor, failure to incorporate important outcomes, poor study reporting, and various sources of heterogeneity. Future research directions in terms of conducting additional trials in the vaccination context, improving methodological quality and rigor, assessment of global acceptability and feasibility of interventions, and inclusion of outcomes that stakeholders consider to be important (eg, compliance) are recommended. Given concerns about pain and fear are known contributors to vaccine hesitancy, improving and expanding this evidence base will be integral to broader efforts to improve vaccine compliance and public health worldwide. PMID- 26352916 TI - Interventions for Individuals With High Levels of Needle Fear: Systematic Review of Randomized Controlled Trials and Quasi-Randomized Controlled Trials. AB - BACKGROUND: This systematic review evaluated the effectiveness of exposure-based psychological and physical interventions for the management of high levels of needle fear and/or phobia and fainting in children and adults. DESIGN/METHODS: A systematic review identified relevant randomized and quasi-randomized controlled trials of children, adults, or both with high levels of needle fear, including phobia (if not available, then populations with other specific phobias were included). Critically important outcomes were self-reported fear specific to the feared situation and stimulus (psychological interventions) or fainting (applied muscle tension). Data were pooled using standardized mean difference (SMD) or relative risk with 95% confidence intervals. RESULTS: The systematic review included 11 trials. In vivo exposure-based therapy for children 7 years and above showed benefit on specific fear (n=234; SMD: -1.71 [95% CI: -2.72, -0.7]). In vivo exposure-based therapy with adults reduced fear of needles posttreatment (n=20; SMD: -1.09 [-2.04, -0.14]) but not at 1-year follow-up (n=20; SMD: -0.28 [ 1.16, 0.6]). Compared with single session, a benefit was observed for multiple sessions of exposure-based therapy posttreatment (n=93; SMD: -0.66 [-1.08, 0.24]) but not after 1 year (n=83; SMD: -0.37 [-0.87, 0.13]). Non in vivo e.g., imaginal exposure-based therapy in children reduced specific fear posttreatment (n=41; SMD: -0.88 [-1.7, -0.05]) and at 3 months (n=24; SMD: -0.89 [-1.73, 0.04]). Non in vivo exposure-based therapy for adults showed benefit on specific fear (n=68; SMD: -0.62 [-1.11, -0.14]) but not procedural fear (n=17; SMD: 0.18 [ 0.87, 1.23]). Applied tension showed benefit on fainting posttreatment (n=20; SMD: -1.16 [-2.12, -0.19]) and after 1 year (n=20; SMD: -0.97 [-1.91, -0.03]) compared with exposure alone. CONCLUSIONS: Exposure-based psychological interventions and applied muscle tension show evidence of benefit in the reduction of fear in pediatric and adult populations. PMID- 26352919 TI - Procedural and Physical Interventions for Vaccine Injections: Systematic Review of Randomized Controlled Trials and Quasi-Randomized Controlled Trials. AB - BACKGROUND: This systematic review evaluated the effectiveness of physical and procedural interventions for reducing pain and related outcomes during vaccination. DESIGN/METHODS: Databases were searched using a broad search strategy to identify relevant randomized and quasi-randomized controlled trials. Data were extracted according to procedure phase (preprocedure, acute, recovery, and combinations of these) and pooled using established methods. RESULTS: A total of 31 studies were included. Acute infant distress was diminished during intramuscular injection without aspiration (n=313): standardized mean difference (SMD) -0.82 (95% confidence interval [CI]: -1.18, -0.46). Injecting the most painful vaccine last during vaccinations reduced acute infant distress (n=196): SMD -0.69 (95% CI: -0.98, -0.4). Simultaneous injections reduced acute infant distress compared with sequential injections (n=172): SMD -0.56 (95% CI: -0.87, 0.25). There was no benefit of simultaneous injections in children. Less infant distress during the acute and recovery phases combined occurred with vastus lateralis (vs. deltoid) injections (n=185): SMD -0.70 (95% CI: -1.00, -0.41). Skin-to-skin contact in neonates (n=736) reduced acute distress: SMD -0.65 (95% CI: -1.05, -0.25). Holding infants reduced acute distress after removal of the data from 1 methodologically diverse study (n=107): SMD -1.25 (95% CI: -2.05, 0.46). Holding after vaccination (n=417) reduced infant distress during the acute and recovery phases combined: SMD -0.65 (95% CI: -1.08, -0.22). Self-reported fear was reduced for children positioned upright (n=107): SMD -0.39 (95% CI: 0.77, -0.01). Non-nutritive sucking (n=186) reduced acute distress in infants: SMD -1.88 (95% CI: -2.57, -1.18). Manual tactile stimulation did not reduce pain across the lifespan. An external vibrating device and cold reduced pain in children (n=145): SMD -1.23 (95% CI: -1.58, -0.87). There was no benefit of warming the vaccine in adults. Muscle tension was beneficial in selected indices of fainting in adolescents and adults. CONCLUSIONS: Interventions with evidence of benefit in select populations include: no aspiration, injecting most painful vaccine last, simultaneous injections, vastus lateralis injection, positioning interventions, non-nutritive sucking, external vibrating device with cold, and muscle tension. PMID- 26352922 TI - Lewis Acid Mediated Trifluoromethylthio Lactonization/Lactamization. AB - A highly selective Lewis acid mediated trifluoromethylthio lactonization/lactamization of olefins is described. The reaction was proposed to proceed via a thiiranium ion intermediate, which was further attacked by the carboxylic acid or amide to generate the corresponding trifluoromethylthiolated lactone/lactam. PMID- 26352920 TI - Far From "Just a Poke": Common Painful Needle Procedures and the Development of Needle Fear. AB - BACKGROUND: Vaccine injections are the most common painful needle procedure experienced throughout the lifespan. Many strategies are available to mitigate this pain; however, they are uncommonly utilized, leading to unnecessary pain and suffering. Some individuals develop a high level of fear and subsequent needle procedures are associated with significant distress. OBJECTIVE: The present work is part of an update and expansion of a 2009 knowledge synthesis to include the management of vaccine-related pain across the lifespan and the treatment of individuals with high levels of needle fear. This article will provide a conceptual foundation for understanding: (a) painful procedures and their role in the development and maintenance of high levels of fear; (b) treatment strategies for preventing or reducing the experience of pain and the development of fear; and (c) interventions for mitigating high levels of fear once they are established. RESULTS: First, the general definitions, lifespan development and functionality, needle procedure-related considerations, and assessment of the following constructs are provided: pain, fear, anxiety, phobia, distress, and vasovagal syncope. Second, the importance of unmitigated pain from needle procedures is highlighted from a developmental perspective. Third, the prevalence, course, etiology, and consequences of high levels of needle fear are described. Finally, the management of needle-related pain and fear are outlined to provide an introduction to the series of systematic reviews in this issue. DISCUSSION: Through the body of work in this supplement, the authors aim to provide guidance in how to treat vaccination-related pain and its sequelae, including high levels of needle fear. PMID- 26352921 TI - Simple Psychological Interventions for Reducing Pain From Common Needle Procedures in Adults: Systematic Review of Randomized and Quasi-Randomized Controlled Trials. AB - BACKGROUND: This systematic review evaluated the effectiveness of simple psychological interventions for managing pain and fear in adults undergoing vaccination or related common needle procedures (ie, venipuncture/venous cannulation). DESIGN/METHODS: Databases were searched to identify relevant randomized and quasi-randomized controlled trials. Self-reported pain and fear were prioritized as critically important outcomes. Data were combined using standardized mean difference (SMD) or relative risk (RR) with 95% confidence intervals (CI). RESULTS: No studies involving vaccination met inclusion criteria; evidence was drawn from 8 studies of other common needle procedures (eg, venous cannulation, venipuncture) in adults. Two trials evaluating the impact of neutral signaling of the impending procedure (eg, "ready?") as compared with signaling of impending pain (eg, "sharp scratch") demonstrated lower pain when signaled about the procedure (n=199): SMD=-0.97 (95% CI, -1.26, -0.68), after removal of 1 trial where self-reported pain was significantly lower than the other 2 included trials. Two trials evaluated music distraction (n=156) and demonstrated no difference in pain: SMD=0.10 (95% CI, -0.48, 0.27), or fear: SMD=-0.25 (95% CI, 0.61, 0.10). Two trials evaluated visual distraction and demonstrated no difference in pain (n=177): SMD=-0.57 (95% CI, -1.82, 0.68), or fear (n=81): SMD= 0.05 (95% CI, -0.50, 0.40). Two trials evaluating breathing interventions found less pain in intervention groups (n=138): SMD=-0.82 (95% CI, -1.21, -0.43). The quality of evidence across all trials was very low. CONCLUSIONS: There are no published studies of simple psychological interventions for vaccination pain in adults. There is some evidence of a benefit from other needle procedures for breathing strategies and neutral signaling of the start of the procedure. There is no evidence for use of music or visual distraction. PMID- 26352923 TI - Right Ventricular Angiogenesis is an Early Adaptive Response to Chronic Hypoxia Induced Pulmonary Hypertension. AB - OBJECTIVE: Myocardial angiogenesis is presumed to play a role in RV adaptation to PH, though definitive evidence and functional correlations are lacking. We aimed to use definitive methods to correlate RV angiogenesis, hypertrophy, and function in a murine PH model. METHODS: Mice were exposed to CH for 21 days to induce PH and RV remodeling. We used unbiased stereology and flow cytometry to quantify angiogenesis and myocyte hypertrophy, and pressure-volume loops to measure RV function. RESULTS: Within seven days, RV-specific increases in total capillary length (10,576 +/- 2574 cm vs. 6822 +/- 1379 cm; p = 0.02), surface area (10 +/- 3.3 cm(2) vs. 4.9 +/- 1.5 cm(2) ; p = 0.01), and volume (0.0013 +/- 0.0005 cm(3) vs. 0.0006 +/- 0.0001 cm(3) ; p = 0.02) were observed, and RV EC proliferation increased nearly 10-fold. Continued exposure led to progressive RVH without additional angiogenesis. RV function was preserved, but activation of hypoxia dependent gene expression was observed in both ventricles after 21 days. CONCLUSIONS: Early RV remodeling in CH-PH is associated with RV angiogenesis and preserved RV function. Continued CH-PH is associated with RVH but not angiogenesis, leading to biventricular activation of hypoxia-dependent gene expression. PMID- 26352924 TI - Tailoring the surface-oxygen defects of a tin dioxide support towards an enhanced electrocatalytic performance of platinum nanoparticles. AB - Tin-dioxide nanofacets (SnO2 NFs) are crystal-engineered so that oxygen defects on the maximal {113} surface are long-range ordered to give rise to a non occupied defect band (DB) in the bandgap. SnO2 NFs-supported platinum nanoparticles exhibit an enhanced ethanol-electrooxidation activity due to the promoted charge-transport via the DB at the metal-semiconductor interface. PMID- 26352926 TI - Evaluation of Liver Biomarkers as Prognostic Factors for Outcomes to Yttrium-90 Radioembolization of Primary and Secondary Liver Malignancies. AB - The objective of this study was to examine indicators of liver function and inflammation for prognostic value in predicting outcomes to yttrium-90 radioembolization (RE). In a retrospective analysis, markers of liver function and inflammation, biomarkers required to stage liver function and inflammation, and data regarding survival, tumor response, and progression after RE were recorded. Univariate regression models were used to investigate the prognostic value of liver biomarkers in predicting outcome to RE as measured by survival, tumor progression, and radiographic and biochemical tumor response. Markers from all malignancy types were analyzed together. A subgroup analysis was performed on markers from patients with metastatic colorectal cancer. A total of 31 patients received RE from 2004 to 2014. Median survival after RE for all malignancies combined was 13.6 months (95% CI: 6.7-17.6 months). Results from an exploratory analysis of patient data suggest that liver biomarkers, including albumin concentrations, international normalized ratio, bilirubin concentrations, and the model for end-stage liver disease score, possess prognostic value in predicting outcomes to RE. PMID- 26352925 TI - Characterization of Vis Toxin, a Novel ADP-Ribosyltransferase from Vibrio splendidus. AB - Vis toxin was identified by a bioinformatics strategy as a putative virulence factor produced by Vibrio splendidus with mono-ADP-ribosyltransferase activity. Vis was purified to homogeneity as a 28 kDa single-domain enzyme and was shown to possess NAD(+)-glycohydrolase [KM(NAD(+)) = 276 +/- 12 MUM] activity and with an R-S-E-X-E motif; it targets arginine-related compounds [KM(agmatine) = 272 +/- 18 mM]. Mass spectrometry analysis revealed that Vis labels l-arginine with ADP ribose from the NAD(+) substrate at the amino nitrogen of the guanidinium side chain. Vis is toxic to yeast when expressed in the cytoplasm under control of the CUP1 promotor, and catalytic variants lost the ability to kill the yeast host, indicating that the toxin exerts its lethality through its enzyme activity. Several small molecule inhibitors were identified from a virtual screen, and the most potent compounds were found to inhibit the transferase activity of the enzyme with Ki values ranging from 25 to 134 MUM. Inhibitor compound M6 bears the necessary attributes of a solid candidate as a lead compound for therapeutic development. Vis toxin was crystallized, and the structures of the apoenzyme (1.4 A) and the enzyme bound with NAD(+) (1.8 A) and with the M6 inhibitor (1.5 A) were determined. The structures revealed that Vis represents a new subgroup within the mono-ADP-ribosyltransferase toxin family. PMID- 26352928 TI - The Importance of Being Honest. PMID- 26352927 TI - Development and Characterization of a New Antipeptide Monoclonal Antibody Directed to Human CD20 Antigen. AB - The rapid expansion of immunotherapeutic approaches for treatment of various diseases, including cancers, has been greatly facilitated by the invention of new generation of antibodies. Clinical studies have indicated that anti-CD20 mAb based therapies represent an effective treatment for various diseases with overexpression of CD20 on their cell surface, such as non-Hodgkin's lymphoma, hemolytic anemia, as well as autoimmune diseases like rheumatoid arthritis. Technically, due to a short extra membrane domain, the recombinant CD20 protein is a difficult antigen to raise immune responses. In search for new monoclonal antibodies, the authors used an antigenic polypeptide, which yielded numbers of new binders that may lead to production of anti-CD20 antibodies, with improved diagnostic or clinical attributes. Mice were immunized with extra membrane loop of human CD20 (exCD20) polypeptide. The exCD20 antigen showed a desired immune response and was able to develop a monoclonal antibody, 3B4C10, which reacted well with peptide antigen as well as native antigen on the surface of Raji B-cell line. The antibody 3B4C10 with a balanced K(on) and K(off) may be applicable in the construction of affinity columns or beads for isolation and purification of CD20-positive cells and cancer stem cells. PMID- 26352929 TI - Time interval after ischaemic preconditioning affects neuroprotection and gliosis in the gerbil hippocampal CA1 region induced by transient cerebral ischaemia. AB - OBJECTIVES: Ischaemic preconditioning (IPC) can increase ischaemic tolerance of the central nervous system (CNS) to a subsequent longer or lethal period of transient ischaemia. In this study, we examined neuroprotective effects of time intervals after IPC against ischaemic insult in the hippocampus. METHODS: Animals were randomly assigned to six groups; sham-operated-group, ischaemia-operated group, and three IPC (12 hours, 1- and 2-day intervals after IPC) plus ischaemia groups (IPC-12 hour, 1 and 2-day interval-ischaemia-operated-groups). For neuroprotection, we carried out cresyl violet (CV) staining neuronal nuclei (NeuN) immunohistochemistry and Fluoro-Jade B histofluorescence staining. In addition, we examined gliosis using immunohistochemistry for GFAP (a marker for astrocytes) and Iba-1 (a marker for microglia). RESULTS: A significant loss of neurons was observed in the stratum pyramidale (SP) of the hippocampal CA1 region (CA1) in the ischaemia-operated-group and IPC-12 hours interval-ischaemia operated-groups. In the IPC-1 day interval-ischaemia-operated-group, CA1 pyramidal neurons were well protected from ischaemic insult; the neuroprotective effect in the IPC-2 day interval-ischaemia-operated-group was less than that in the IPC-1 day interval-ischaemia-operated-group. On the other hand, we observed changes in glial cells (astrocytes and microglia) in the CA1 of all groups. The distribution pattern of glial cells only in the IPC-1 day interval-ischaemia operated-group was similar to that in the sham-group. CONCLUSION: In brief, our findings indicate that 1 day after IPC displays a mighty neuroprotection and shows an inhibition of glial activation in the CA1 induced by transient ischaemic insult. PMID- 26352930 TI - Mineral oil and synthetic hydrocarbons in cosmetic lip products. AB - OBJECTIVE: Lipsticks and lip care products may contain saturated hydrocarbons which either stem from mineral oil saturated hydrocarbons (MOSH) or are synthetic, that is polyolefin oligomeric saturated hydrocarbons (POSH). Some of these hydrocarbons are strongly accumulated and form granulomas in human tissues, which prompted Cosmetics Europe (former Colipa) to issue a recommendation for their use in lip care and oral products. From 2012 to 2014, MOSH+POSH were determined in 175 cosmetic lip products taken from the Swiss market in order to estimate their contribution to human exposure. METHODS: Mineral oil saturated hydrocarbons and POSH were extracted and analysed by GC with FID. Areas were integrated as a total as well as by mass ranges with cuts at n-C25 and n-C34 to characterize the molecular mass distribution. RESULTS: About 68% of the products contained at least 5% MOSH+POSH (total concentration). For regular users, these products would be major contributors to their MOSH+POSH exposure. About 31% of the products contained more than 32% MOSH+POSH. Their regular usage would amount in an estimated MOSH+POSH exposure exceeding the highest estimated dietary exposure. The majority of the products contained hydrocarbons with a molecular mass range which was not in line with the recommendations of Cosmetics Europe. CONCLUSIONS: Taking into account that material applied to the lips largely ends up being ingested, MOSH and POSH levels should be reduced in the majority of cosmetic lip products. As the extensive evaluation of the data available on MOSH (EFSA J., 10, 2012, 2704) did not enable the specification of limits considered as safe, the present level of dietary exposure and its evaluation as 'of potential concern' provide the relevant bench mark, which means that lip products should contain clearly less than 5% MOSH+POSH. PMID- 26352931 TI - Silk Gland Gene Expression during Larval-Pupal Transition in the Cotton Leaf Roller Sylepta derogata (Lepidoptera: Pyralidae). AB - The cotton leaf roller, Sylepta derogata, is a silk-producing insect pest. While young larvae feed on the underside of leaves, the older ones roll cotton leaves and feed on the leaf edges, which defoliates cotton plants. The larvae produce silk to stabilize the rolled leaf and to balloon from used to new leaves. Despite the significance of silk in the biology of pest insect species, there is virtually no information on the genes involved in their silk production. This is a substantial knowledge gap because some of these genes may be valuable targets for developing molecular pest management technologies. We addressed the gap by posing the hypothesis that silk gland gene expression changes during the transition from larvae to pupae. We tested our hypothesis using RNA-seq to investigate changes in silk gland gene expression at three developmental stages, 5th instar larvae (silk producing; 15,445,926 clean reads), prepupae (reduced silk producing; 13,758,154) and pupae (beyond silk producing; 16,787,792). We recorded 60,298 unigenes and mapped 50,158 (larvae), 48,415 (prepupae) and 46,623 (pupae) of them to the NCBI database. Most differentially expressed genes in the 5th instar larvae/prepupae libraries were relevant to nucleotide synthesis and maintenance of silk gland function. We identified down-regulated transcriptional factors and several genes involved in silk formation in the three libraries and verified the expression pattern of eight genes by qPCR. The developmental- and tissue-specific expression patterns of the fibroin light chain gene showed it was highly expressed during the larval silk-producing stage. We recorded highest expression of this gene in the larval silk gland, compared to other tissues, including midgut, hindgut, epidermis, Malpighian tubes, hemolymph and fat body. These data are a genetic resource to guide selection of key genes that may be targeted for in planta and other gene-silencing technologies for sustainable cotton agriculture. PMID- 26352932 TI - Efficacy of Albendazole-Chitosan Microsphere-based Treatment for Alveolar Echinococcosis in Mice. AB - This study aimed to investigate the pharmacology and anti-parasitic efficacy of albendazole-chitosan microspheres (ABZ-CS-MPs) for established intraperitoneal infections of Echinococcus multilocularis metacestodes in an experimental murine model. Male outbred Kunming mice infected with E. multilocularis Metacestodes were administered with three ABZ formulations, namely, ABZ-CS-MPs, Liposome Albendazole (L-ABZ), and albendazole tablet (ABZ-T). Each of the ABZ formulations was given orally at three different doses of 37.5, 75, and 150 mg/kg, three times a week for 12 weeks postinfection. After administering the drugs, we monitored the pharmacological performance and anti-parasitic efficacy of ABZ-CS-MPs compared with L-ABZ, and ABZ-T treated mice. ABZ-CS-MPs reduced the weight of tissues containing E. multilocularis metacestodes most effectively compared with the ABZ-T group and untreated controls. Metacestode grown was Highly suppressed during treatment with ABZ-CS-MPs. Significantly higher plasma levels of ABZ metabolites were measured in mice treated with ABZ-CS-MPs or L-ABZ compared with ABZ-T. In particular, enhanced ABZ-sulfoxide concentration profiles were observed in the mice given 150 mg/kg of ABZ-CS-MPs, but not in the mice treated with L ABZ. Histological examination showed that damages caused disorganization of both the germinal and laminated layers of liver hyatid cysts, demolishing their characteristic structures after treatment with ABZ-CS-MPs or L-ABZ. Over time, ABZ-CS-MPs treatment induced a shift from Th2-dominant to Th1-dominant immune response. CS-MPs As a new carrier exhibited improved absorption and increased bioavailability of ABZ in the treatment of E. multilocularis infections in mice. PMID- 26352933 TI - Chromium Biosorption from Cr(VI) Aqueous Solutions by Cupressus lusitanica Bark: Kinetics, Equilibrium and Thermodynamic Studies. AB - The present study investigated the kinetics, equilibrium and thermodynamics of chromium (Cr) ion biosorption from Cr(VI) aqueous solutions by Cupressus lusitanica bark (CLB). CLB total Cr biosorption capacity strongly depended on operating variables such as initial Cr(VI) concentration and contact time: as these variables rose, total Cr biosorption capacity increased significantly. Total Cr biosorption rate also increased with rising solution temperature. The pseudo-second-order model described the total Cr biosorption kinetic data best. Langmuir's model fitted the experimental equilibrium biosorption data of total Cr best and predicted a maximum total Cr biosorption capacity of 305.4 mg g(-1). Total Cr biosorption by CLB is an endothermic and non-spontaneous process as indicated by the thermodynamic parameters. Results from the present kinetic, equilibrium and thermodynamic studies suggest that CLB biosorbs Cr ions from Cr(VI) aqueous solutions predominantly by a chemical sorption phenomenon. Low cost, availability, renewable nature, and effective total Cr biosorption make CLB a highly attractive and efficient method to remediate Cr(VI)-contaminated water and wastewater. PMID- 26352934 TI - Active Compounds Against Anopheles minimus Carboxypeptidase B for Malaria Transmission-Blocking Strategy. AB - Malaria transmission-blocking compounds have been studied to block the transmission of malaria parasites, especially the drug-resistant Plasmodium. Carboxypeptidase B (CPB) in the midgut of Anopheline mosquitoes has been demonstrated to be essential for the sexual development of Plasmodium in the mosquito. Thus, the CPB is a potential target for blocking compounds. The aim of this research was to screen compounds from the National Cancer Institute (NCI) diversity dataset and U.S. Food and Drug Administration (FDA)-approved drugs that could reduce the Anopheles CPB activity. The cDNA fragment of cpb gene from An. minimus (cpbAmi) was amplified and sequenced. The three-dimensional structure of CPB was predicted from the deduced amino acid sequence. The virtual screening of the compounds from NCI diversity set IV and FDA-approved drugs was performed against CPBAmi. The inhibition activity against CPBAmi of the top-scoring molecules was characterized in vitro. Three compounds-NSC-1014, NSC-332670, and aminopterin with IC50 at 0.99 mM, 1.55 mM, and 0.062 mM, respectively-were found to significantly reduce the CPBAmi activity. PMID- 26352935 TI - Behavioral Response of Aedes aegypti (Diptera: Culicidae) Larvae to Synthetic and Natural Attractants and Repellents. AB - Aedes aegypti (L.) (Diptera: Culicidae) is the key vector of three important arboviral diseases: dengue, yellow fever, and chikungunya. Immature stages of this species inhabit human-made containers placed in residential landscapes. In this study, we evaluated a few compounds in a sensitive behavioral assay with Ae. aegypti larvae. The orientation of larvae to different compounds was surveyed using a performance index (PI). The PI represents the response to each odorant, where a value of +1 is indicative of full attraction and -1 represents complete repulsion. The widely used insect repellent N, N-diethyl-m-toluamide elicited a significantly negative PI, as did acetophenone and indole. A yeast extract, a known food source, elicited a significantly positive PI, as did 2-methylphenol, 1 octen-3-ol, 3-methylphenol, and fish food. On the other hand, no response was observed for the essential oil of Eucalyptus grandis x Eucalyptus camaldulensis at the concentration evaluated. Pretreatment of larvae with N-ethylmaleimide and ablation of the antennae resulted in a suppression of behavioral responses. The overall mobility of ablated larvae was indistinguishable from unablated controls, and absence of any visible locomotor dysfunction was observed. This work is a contribution to the study of the chemical ecology of disease vectors with the aim of developing more efficient tools for surveillance and control.Natural and synthetic compounds attractive to Ae. aegypti larvae should be incorporated into integrated pest management programs through the use of baited traps or by improving the efficacy of larvicides commonly used in control campaigns. PMID- 26352936 TI - Improving Patient Satisfaction and Quality of Care During Aesthetic Use of Botulinum Toxin. PMID- 26352937 TI - Early Childhood Development and Schooling Attainment: Longitudinal Evidence from British, Finnish and Philippine Birth Cohorts. AB - BACKGROUND: While recent literature has highlighted the importance of early childhood development for later life outcomes, comparatively little is known regarding the relative importance of early physical and cognitive development in predicting educational attainment cross-culturally. METHODS: We used prospective data from three birth cohorts: the Northern Finland Birth Cohort of 1986 (NFBC1986), the 1970 British Cohort Study (BCS1970), and the Cebu Longitudinal Health and Nutrition Survey of 1983 (CLHNS) to assess the association of height for-age z-score (HAZ) and cognitive development measured prior to age 8 with schooling attainment. Multivariate linear regression models were used to estimate baseline and adjusted associations. RESULTS: Both physical and cognitive development were highly predictive of adult educational attainment conditional on parental characteristics. The largest positive associations between physical development and schooling were found in the CLHNS (beta = 0.53, 95%-CI: [0.32, 0.74]) with substantially smaller associations in the BCS1970 (beta = 0.10, 95% CI [0.04, 0.16]) and the NFBC1986 (beta = 0.06, 95% CI [-0.05, 0.16]). Strong associations between cognitive development and educational attainment were found for all three cohorts (NFBC1986: beta = 0.22, 95%-CI: [0.12, 0.31], BCS1970: beta = 0.58, 95%-CI: [0.52, 0.64], CLHNS: beta = 1.08, 95%-CI: [0.88, 1.27]). Models jointly estimating educational associations of physical and cognitive development demonstrated weaker associations for physical development and minimal changes for cognitive development. CONCLUSION: The results indicate that although physical and cognitive early development are both important predictors of educational attainment, cognitive development appears to play a particularly important role. The large degree of heterogeneity in the observed effect sizes suggest that the importance of early life physical growth and cognitive development is highly dependent on socioeconomic and institutional contexts. PMID- 26352938 TI - Effects of Acute Endurance Exercise Performed in the Morning and Evening on Inflammatory Cytokine and Metabolic Hormone Responses. AB - PURPOSE: To compare the effects of endurance exercise performed in the morning and evening on inflammatory cytokine responses in young men. METHODS: Fourteen healthy male participants aged 24.3 +/- 0.8 years (mean +/- standard error) performed endurance exercise in the morning (0900-1000 h) on one day and then in the evening (1700-1800 h) on another day with an interval of at least 1 week between each trial. In both the morning and evening trials, the participants walked for 60 minutes at approximately 60% of the maximal oxygen uptake (VO2max) on a treadmill. Blood samples were collected to determine hormones and inflammatory cytokines at pre-exercise, immediately post exercise, and 2 h post exercise. RESULTS: Plasma interleukin (IL)-6 and adrenaline concentrations were significantly higher immediately after exercise in the evening trial than in the morning trial (P < 0.01, both). Serum free fatty acids concentrations were significantly higher in the evening trial than in the morning trial at 2 h after exercise (P < 0.05). Furthermore, a significant correlation was observed between the levels of IL-6 immediately post-exercise and free fatty acids 2 h post exercise in the evening (r = 0.68, P < 0.01). CONCLUSIONS: These findings suggest that the effect of acute endurance exercise in the evening enhances the plasma IL 6 and adrenaline concentrations compared to that in the morning. In addition, IL 6 was involved in increasing free fatty acids, suggesting that the evening is more effective for exercise-induced lipolysis compared with the morning. PMID- 26352939 TI - Fluorescence polarization measurement system using a liquid crystal layer and an image sensor. AB - The detection system which enables simultaneous fluorescence polarization (FP) measurement of multiple samples was proposed and proven by a proof-of-concept experiment on the viscosity dependence of FP of fluorescein sample in water ethylene glycol solution and another experiment on the FP immunoassay of prostaglandin E2 sample. The measurement principle of FP is based on the synchronization between the orientation of the liquid crystal molecules and the sampling frequency of a CCD. This report is the first description of the simultaneous FP measurement of multiple samples. This system has a great potential for equipment miniaturization and price reduction as well as providing simultaneous FP measurement of multiple samples. PMID- 26352940 TI - Paracetamol as a Post Prandial Marker for Gastric Emptying, A Food-Drug Interaction on Absorption. AB - The use of paracetamol as tool to determine gastric emptying was evaluated in a cross over study. Twelve healthy volunteers were included and each of them consumed two low and two high caloric meals. Paracetamol was mixed with a liquid meal and administered by a nasogastric feeding tube. The post prandial paracetamol plasma concentration time curve in all participants and the paracetamol concentration in the stomach content in six participants were determined. It was found that after paracetamol has left the stomach, based on analysis of the stomach content, there was still a substantial rise in the plasma paracetamol concentration time curve. Moreover, the difference in gastric emptying between high and low caloric meals was missed using the plasma paracetamol concentration time curve. The latter curves indicate that (i) part of the paracetamol may leave the stomach much quicker than the meal and (ii) part of the paracetamol may be relatively slowly absorbed in the duodenum. This can be explained by the partition of the homogenous paracetamol-meal mixture in the stomach in an aqueous phase and a solid bolus. The aqueous phase leaves the stomach quickly and the paracetamol in this phase is quickly absorbed in the duodenum, giving rise to the relatively steep increase of the paracetamol concentration in the plasma. The bolus leaves the stomach relatively slowly, and encapsulation by the bolus results in relatively slow uptake of paracetamol from the bolus in the duodenum. These findings implicate that paracetamol is not an accurate post prandial marker for gastric emptying. The paracetamol concentration time curve rather illustrates the food-drug interaction on absorption, which is not only governed by gastric emptying. TRIAL REGISTRATION: ClinicalTrials.gov NCT01335503 Nederlands Trial Register NTR2780. PMID- 26352941 TI - Statement on Exercise Testing in Cystic Fibrosis. AB - This statement summarizes the information available on specific exercise test protocols and outcome parameters used in patients with cystic fibrosis (CF) and provides expert consensus recommendations for protocol and performance of exercise tests and basic interpretation of results for clinicians. The conclusions were reached employing consensus meetings and a wide-band Delphi process. Although data on utility are currently limited, standardized exercise testing provides detailed information on physiological health, allows screening for exercise-related adverse reactions and enables exercise counselling. The Godfrey Cycle Ergometer Protocol with monitoring of oxygen saturation and ventilatory gas exchange is recommended for exercise testing in people 10 years and older. Cycle ergometry only with pulse oximetry using the Godfrey protocol or treadmill exercise with pulse oximetry - preferably with measurement of gas exchange - are second best options. Peak oxygen uptake, if assessed, and maximal work rate should be reported as the primary measure of exercise capacity. The final statement was reviewed by the European Cystic Fibrosis society and revised based on the comments received. The document was endorsed by the European Respiratory Society. PMID- 26352942 TI - [Sexually vulnerable women: could reversible long-lasting contraception be the solution?]. PMID- 26352943 TI - [Frequency and associated factors of phantom breast syndrome in women submitted to mastectomy for breast cancer]. AB - PURPOSE: To evaluate the frequency and risk factors for the development of phantom breast syndrome in patients submitted to mastectomy after breast cancer treatment. METHODS: A cohort study of women undergoing treatment at the Hospital of Cancer III, National Cancer Institute Jose Alencar Gomes da Silva (INCA) from September 2008 to June 2009. PBS was considered based on report of phantom breast sensation and/or phantom breast pain. The study was approved by the Research Ethics Committee of the INCA (015/08). Descriptive analysis using absolute and relative frequency was performed. To evaluate the association between PBS and potential risk factors, univariate analysis was performed by means of odds ratios (OR) with respective 95% confidence intervals (95%CI). RESULTS: A total of 88 patients were included. The frequency of PBS observed was 44.3 at 45 days (first follow-up) and 18.2% at 2 years (last follow-up). Most women reported phantom breast syndrome in all segments (37.1; 30.1 and 22%). During the six month follow up, women under the age of 60 years had a 3.93 times higher risk of PBS (OR=3.9; 95%CI 1.4-10.5) and those with higher education (8 years or more of study) had a higher risk of developing PBS (OR=2.6; 95%CI 1.01-6.8). CONCLUSION: The study population had a high frequency of PBS, which decreased over postoperative follow up. Its occurrence after six months was higher among younger and more educated women. PMID- 26352944 TI - Increased oxidative stress markers may be a promising indicator of risk for primary ovarian insufficiency: a cross-sectional case control study. AB - PURPOSE: The aim of this study was to evaluate serum levels of inducible nitric oxide synthase (INOS), myeloperoxidase (MPO), total antioxidant status (TAS), and total oxidative status (TOS) in women with primary ovarian insufficiency (POI) and to compare them with healthy fertile women. We also examined the possible risk factors associated with POI. METHODS: This cross-sectional case control study was conducted in Zekai Tahir Burak Women's Health Education and Research Hospital. The study population consisted of 44 women with POI (study group) and 36 healthy fertile women (control group). In all patients, serum levels of INOS, MPO, TAS, and TOS were determined. INOS and MPO levels were measured by enzyme linked immunosorbent assay whereas colorimetric method was used for evaluating TAS and TOS levels. Age, body mass index (BMI), obstetric history, smoking status, family history, comorbidities, sonographic findings, complete blood count values, C-reactive protein and baseline hormone levels were also analyzed. Student's t-test or Mann-Whitney U test was used to compare continuous variables between the groups; categorical data were evaluated by using Pearson chi2 or Fisher exact test, when appropriate. Binary logistic regression method was used to identify risk factors for POI. RESULTS: We found significantly elevated levels of INOS (234.1+/-749.5 versus133.8+/-143.0; p=0.005), MPO (3,438.7+/-1,228.6 versus 2,481.9+/-1,230.1; p=0.001), and TOS (4.3+/-1.4 versus 3.6+/-1.4; p=0.02) in the sera of the study group when compared to the BMI-age matched control group. However, difference in serum levels of TAS were not significant between the 2 groups (1.7+/-0.2 versus 1.6+/-0.2; p=0.15). Logistic regression method demonstrated that BMI <25 kg/m2, nulliparity, family history of POI, smoking, and elevated serum levels of INOS, MPO, and TOS were independent risk factors for POI. CONCLUSION: We found an increase in INOS, MPO, and TOS in women with POI. These serum markers may be promising in early diagnosis of POI. Further large scale studies are required to determine whether oxidative stress markers have a role in diagnosing POI. PMID- 26352945 TI - [Prevalence of congenital and perinatal infection in HIV positive pregnant in Belo Horizonte metropolitan region]. AB - PURPOSE: To evaluate the prevalence of toxoplasmosis, rubella, cytomegalovirus, hepatitis B&C and syphilis (Torchs) in a cohort pregnant women and to identify the sociodemographic, clinical and laboratory factors. METHODS: A total of 1,573 HIV-infected pregnant women from a Brazilian metropolitan region were studied between 1998 and 2013. The results of serological tests were available for 704 (44.8%) pregnant women. Pregnant women were considered to be Torchs positive (Gtp) when they had positive results for at least one of these infections, and to be Torchs negative (Gtn) when they had negative results for all of them. Maternal covariables were: age, marital status, educational level, time and mode of infection, CD4 lymphocyte count, viral load at delivery, and use of antiretroviral therapy (ARV). Neonatal covariables were: HIV infection, prematurity, low birth weight, neonatal complications, abortion and neonatal death. Odds ratios with 95% confidence interval were used to quantify the association between maternal and neonatal variables and the presence of Torchs. RESULTS: Among 704 pregnant women, 70 (9.9%; 95%CI 7.8-12.4) had positive serological tests for any Torchs factor. The individual prevalence rates were: 1.5% (10/685) for toxoplasmosis; 1.3% (8/618) for rubella; 1.3% (8/597) for cytomegalovirus; 0.9% (6/653) for hepatitis B and 3.7% (20/545) for hepatitis C; and 3.8% (25/664) for syphilis. The HIV Vertical HIV transmission was 4.6% among Gtp pregnant women and 1.2% among Gtn women. Antiretroviral therapy (ARV), vertical transmission, low birth weight and neonatal complications were significantly associated with Torchs positivity in univariate analysis. CONCLUSIONS: The Torchs prevalence found in the study was high for some infections. These findings emphasize the need to promote serological Torchs screening for all pregnant women, especially HIV-infected women, so that an early diagnosis can be made and treatment interventions can be implemented to prevent vertical HIV transmission. PMID- 26352946 TI - [Premature labour with or without preterm premature rupture of membranes: maternal, obstetric and neonatal features]. AB - PURPOSE: Evaluation of maternal, obstetrics e neonatal features in both spontaneous preterm births (PTB) with or without preterm premature rupture of membranes (PPROM). METHODS: Retrospective study of single fetus pregnancies with PTB between 2003 and 2012. INCLUSION CRITERIA: PTB associated with ou without PPROM. Exclusion criterias: PTB by medical indication due to fetal/maternal disease and all non accessible or incomplete clinical files. Different characteristics were compared between two groups of PTB: spontaneous PTB without PPROM (sPTB) versusPPROM. Kolmogorov-Smirnov, Levene, chi2, t Student and Mann Withney tests were used for statistical analysis. RESULTS: From 2,393 PTB of single fetus, 1,432 files were analysed, from which 596 were sPTB and 836 PPROM. The socioeconomic conditions were similar in both groups. Multiparity (50.7 versus 40.3%), personal history of previous PTB (20.8 versus10.2%), cervical length (18.2 versus27.2 mm), lower body index mass (23.4 versus 24.3 kg/m2) and higher infectious parameters (Protein C Reactive: 2.2 versus1.2 mg/L; Leukocytes: 13.3 versus 12.4 x109) were more frequent in PBTs (p<0,001). Neonatal outcomes, specially neurologic outcomes (4.7 versus2.8%, p<0,001), were worst in PBTs. CONCLUSION: PTB with or without PPROM has a complex etiology. From all evaluated features in our study, only maternal thinness, multiparity with a previous PTB, the cervical length and worst systemic infections parameters were significant in sPTB. This group also showed worst neonatal outcomes, specially on neurological outcomes. PMID- 26352947 TI - HEMATOLOGIC AND BIOCHEMICAL PARAMETERS OF KELP GULLS (LARUS DOMINICANUS) CAPTURED IN THE CITY OF TALCAHUANO, CHILE. AB - In order to provide tools for future health-based monitoring programs, we developed reference intervals for hematology and plasma biochemistry and partitioned data for sex and season (winter and autumn). Ninety-one physically healthy kelp gulls (Larus dominicanus) were sampled in the city of Talcahuano, Chile, during winter (July-September) of 2007, autumn (April-June) and winter of 2008, and autumn of 2009. After blood sampling, the kelp gulls were euthanized by cervical dislocation. Packed cell volume (PCV), hemoglobin, total plasma protein (TPP), and complete blood count were performed. Alanine amino transferase, gamma glutamyl transpeptidase, lactate dehydrogenase, alkaline phosphatase (ALP), creatinine, urea, calcium, phosphorus, and uric acid were analyzed. No significant differences were found between sexes (P>0.05). When a comparison was made between the two seasons, the values of PCV, TPP, white blood cell, heterophils, eosinophils, and monocytes were significantly higher in winter than in autumn (P<0.05) while and urea and uric acid concentrations were higher in autumn. Heterophils were the predominant circulating leukocyte for all birds. There was no significant difference in body condition between autumn and winter nor between sexes. Body condition showed a significant relationship with TPP and basophil concentration and ALP activity. PMID- 26352948 TI - CIRCULATING CONCENTRATIONS OF THYROID HORMONE IN BELUGA WHALES (DELPHINAPTERUS LEUCAS): INFLUENCE OF AGE, SEX, AND SEASON. AB - Thyroid hormones play a critical physiologic role in regulating protein synthesis, growth, and metabolism. To date, because no published compilation of baseline values for thyroid hormones in beluga whales (Delphinapterus leucas) exists, assessment of thyroid hormone concentrations in this species has been underused in clinical settings. The purpose of this study was to document the concentrations of total thyroxine (tT4) and total triiodothyronine (tT3) in healthy aquarium-maintained and free-ranging beluga whales and to determine the influence of age, sex, and season on the thyroid hormone concentrations. Archived serum samples were collected from healthy aquarium-maintained (n=43) and free ranging (n=39) belugas, and serum tT4 and tT3 were measured using chemiluminescence immunoassay. The mean tT4 concentration in aquarium-maintained belugas was 5.67+/-1.43 MUg/dl and the mean tT3 concentration was 70.72+/-2.37 ng/dl. Sex comparisons showed that aquarium-maintained males had significantly greater tT4 and tT3 (9.70+/-4.48 MUg/dl and 92.65+/-30.55 ng/dl, respectively) than females (7.18+/-2.82 MUg/dl and 77.95+/-20.37 ng/dl) (P=0.004 and P=0.013). Age comparisons showed that aquarium-maintained whales aged 1-5 yr had the highest concentrations of tT4 and tT3 (8.17+/-0.17 MUg/dl and 105.46+/-1.98 ng/dl, respectively) (P=0.002 and P<0.001). tT4 concentrations differed significantly between seasons, with concentrations in winter (4.59+/-1.09 MUg/dl) being significantly decreased compared with spring (P=0.009), summer (P<0.0001), and fall (P<0.0001) concentrations. There was a significant difference in tT4 and tT3 concentrations between aquarium-maintained whales (5.67+/-1.43 MUg/dl and 70.72+/-15.57 ng/dl, respectively) and free-ranging whales (11.71+/-3.36 MUg/dl and 103.38+/-26.45 ng/dl) (P<0.0001 and P<0.001). Clinicians should consider biologic and environmental influences (age, sex, and season) for a more accurate interpretation of thyroid hormone concentrations in belugas. The findings of this study provide a baseline for thyroid health monitoring and comprehensive health assessments in both aquarium-maintained and free-ranging beluga whales. PMID- 26352949 TI - LABORATORY VALIDATION OF A POINT-OF-CARE CARDIAC TROPONIN I ASSAY FOR USE IN WHITE-TAILED DEER (ODOCOILEUS VIRGINIANUS). AB - The VetScan(r) i-STAT(r) 1 Handheld Analyzer and cardiac troponin I (cTnI) cartridges (i-STAT cTnI assay) measured greater median cTnI concentration [cTnI] in free-ranging white-tailed deer (Odocoileus virginianus) hand-injected with anesthetic drugs after physical restraint in Clover traps than in those ground darted with the same drugs. This suggested that Clover trapping induces myocardial damage, bringing the use of this capture method under scrutiny. The purpose of this study was to confirm the validity of the i-STAT cTnI assay in deer before recommending changes in capture methods. Median [cTnI] measured by the i-STAT cTnI assay ([cTnI]i) in heparinized whole blood collected from 52 healthy, reproductively mature, female deer physically restrained in a chute was 0.01 ng/ml (10-90% percentiles: 0.00-0.03 ng/ml; minimum, maximum: 0.00, 0.07 ng/ml); [cTnI]i was 0.00 ng/ml in 42% of the deer. There was no association between [cTnI]i and either clotting or hemolytic index. [cTnI]i was 0.00 ng/ml when deer skeletal muscle homogenate was added to deer blood with [cTnI]i of 0.00 ng/ml, confirming the i-STAT cTnI assay does not detect skeletal muscle troponins. When deer cardiac muscle homogenate was serially diluted with 1) deer blood, 2) deer plasma, and 3) cow blood, [cTnI]i was directly proportional (Y intercept=-0.09, 0.7, and -0.08 ng/ml, respectively; r2>=0.97) to the fraction of homogenate in each sample. Deer cardiac muscle homogenate was diluted with deer blood to produce three samples with low, intermediate, and high [cTnI]i; serial measurements (n=10) performed on each sample yielded coefficients of variation (CVs) of 8, 20, and 11%, respectively. Corresponding CVs when plasma was used as diluent were 13, 9, and 7%, respectively. [cTnI]i increased when plasma with a low [cTnI]i was stored at 20-24 degrees C for 9 days. Three freeze-thaw cycles caused no systematic change in plasma [cTnI]i. PMID- 26352950 TI - PHARMACOKINETICS OF TRAMADOL HYDROCHLORIDE AND ITS METABOLITE O-DESMETHYLTRAMADOL FOLLOWING A SINGLE, ORALLY ADMINISTERED DOSE IN CALIFORNIA SEA LIONS (ZALOPHUS CALIFORNIANUS). AB - Tramadol is a synthetic, centrally acting, opiate-like analgesic that is structurally related to codeine and morphine. The objective of this study was to determine the pharmacokinetics of tramadol hydrochloride and its major active metabolite O-desmethyltramadol (M1) in the California sea lion (Zalophus californianus). A single dose of tramadol was administered orally in fish at 2 mg/kg to a total of 15 wild California sea lions admitted for rehabilitation. Twenty-four total blood samples were collected post drug administration at 10, 20, 30, and 45 min and at 1, 3, 5, 6, 8, 12, and 24 hr. Blood plasma was separated and stored at -80 degrees C until analysis with high-performance liquid chromatography was performed to determine levels of tramadol and M1, the major active metabolite. The results indicate that the plasma levels of parent tramadol are low or negligible during the first 30-45 min and then reach the predicted mean maximum plasma concentration of 358 ng/ml at 1.52 hr. The M1 metabolite was not detectable in 21 of 24 plasma samples, below the level of quantification of 5 ng/ml in one sample, and detectable at 11 and 17 ng/ml in two of the samples. This study suggests that a 2 mg/kg dose would need to be administered every 6-8 hr to maintain concentrations of tramadol above the minimum human analgesic level for mild to moderate pain. Based on dosing simulations, a dose of 4 mg/kg q8 hr or q12 hr, on average, may represent an adequate compromise, but further studies are needed using a larger sample size. Pharmacodynamic studies are warranted to determine if tramadol provides analgesic effects in this species. The potential for tramadol toxicosis at any dose also has not been determined in this species. PMID- 26352951 TI - COMPARISON OF THREE SHORT-TERM IMMOBILIZATION REGIMES IN WILD VERREAUX'S SIFAKAS (PROPITHECUS VERREAUXI): KETAMINE-XYLAZINE, KETAMINE-XYLAZINE-ATROPINE, AND TILETAMINE-ZOLAZEPAM. AB - Although research on lemurid primates in Madagascar has been ongoing for several decades, reports on different drug regimes to immobilize wild lemurs are limited. This study compares the efficacy, reliability, and side effects of ketamine xylazine, ketamine-xylazine-atropine, and tiletamine-zolazepam immobilization in wild Verreaux's sifakas (Propithecus verreauxi). In the course of a long-term study in Kirindy Forest, western Madagascar, eight animals each received a mixture of ketamine (5.32+/-1.71 mg/kg) and xylazine (0.56+/-0.19 mg/kg) (KX; 7 males, 1 female) and ketamine (6.58+/-1.36 mg/kg), xylazine (1.28+/-0.28 mg/kg), and atropine (0.013+/-0.003 mg/kg) (KXA; 5 males, 3 females), respectively, and 14 individuals received tiletamine-zolazepam (7.73+/-1.37 mg/kg) (TZ; 9 males, 5 females). Induction was smooth in all protocols, but showed considerable variation in duration when animals had received KXA. Immobilization as well as recovery lasted significantly longer with TZ than with KX (P<0.05). Occurrence of side effects was not significantly different between the protocols; however, excessive salivation, involuntary muscular contractions, and vocalization only occurred in animals immobilized with TZ. Heart rate measurement at 10 min after onset of complete immobilization yielded significantly higher values if the animals had been immobilized with TZ compared to KX (P<0.05). Heart rate decreased from the first to the second measurement for the KX- and KXA immobilized animals, whereas immobilization with TZ resulted in an increase in heart rate. The results suggest that KX produces good, but short, immobilization in Verreaux's sifakas at approximately 5 mg/kg ketamine and 0.5 mg/kg xylazine and a smoother and shorter recovery phase than 5 to 10 mg/kg TZ, whereas adding atropine to KX did not provide any benefits. PMID- 26352952 TI - PSOROPTES INFESTATION AND TREATMENT IN AN ISOLATED POPULATION OF BIGHORN SHEEP (OVIS CANADENSIS). AB - The authors captured bighorn sheep (Ovis canadensis) comprising a small population in the San Bernardino Mountains of California and evaluated the degree of infestation by mites of the genus Psoroptes for each individual. The animals were treated with two novel methods: amitraz-impregnated collars and cyfluthrin impregnated ear tags and recaptured the following year to evaluate the effect of treatment. The authors compared data on degree of infestation for animals recaptured in the posttreatment year, detected no significant interyear differences in infestation severity scores among animals treated with amitraz or cyfluthrin, and could not detect any differences between treatment types. However, a significant (P<0.10) decreased pattern in severity scores from the beginning to the end of treatments was detected, suggesting a cumulative therapeutic value in repeated annual treatments across the 3-yr period. Additionally, the authors detected a lower median mite severity score between 2000 and a later capture in 2006. These positive outcomes may be the result of previous treatments during 2000-2002, but environmental covariates not accounted for could have been contributing factors. Avermectin drugs with longer release profiles may be a more effective treatment option in this and other small bighorn sheep populations that are compromised with mite infestations. PMID- 26352953 TI - SUMMER AND WINTER VITAMIN D3 LEVELS IN FOUR LEMUR SPECIES HOUSED AT A BRITISH ZOO, WITH REFERENCE TO UVB LEVELS. AB - Serum samples were collected from 18 lemurs of four diurnal/cathemeral species housed with outdoor access at Bristol Zoo Gardens (United Kingdom) to test 25 hydroxy-vitamin D3 (25OHD3) levels as part of the veterinary department's preventative health care program. Samples were collected from each lemur in August 2008 (summer) and January 2009 (winter) to examine the effect of season on 25OHD3 levels. The lemurs were fed commercial primate food and a range of fruit and vegetables, and dietary levels of vitamin D3 remained the same throughout the study period. Statistical analysis showed that the lemurs' summer 25OHD3 values (range 26.7 to >150.0 MUg/L) were significantly higher than their winter 25OHD3 values (range 11.4-87.1 MUg/L). UVB measurements taken during the study period confirmed that UVB levels were significantly higher in summer (mean reading for 1200-1300 GMT time period 153.8 MUW/cm2) compared to winter (mean reading for 1200-1300 GMT time period 19.4 MUW/cm2). The 25OHD3 levels measured were generally found to be high compared to previously published values from wild (free-ranging) lemurs in Madagascar. The most likely explanation for this was the higher vitamin D3 content of the captive lemurs' diet, as UVB levels at the zoo (latitude 51 degrees north) are substantially lower than those that occur in Madagascar (latitude 12 degrees -26 degrees south). No evidence of vitamin D toxicity or deficiency was found in any of the captive lemurs. The results indicate that vitamin D3 levels in lemurs housed with outdoor access in the United Kingdom and by extension, other regions of similar latitude, vary with seasonal environmental UVB levels, in a similar way to the seasonal variations in vitamin D3 observed in humans living in these regions, but that vitamin D levels in this captive lemur population were adequate compared to wild lemur levels, even in winter. PMID- 26352954 TI - COMPARISON OF HIGH-DEFINITION OSCILLOMETRIC AND DIRECT ARTERIAL BLOOD PRESSURE MEASUREMENT IN ANESTHETIZED CHEETAHS (ACINONYX JUBATUS). AB - Blood pressure measurement reveals important insights into the health of conscious and anesthetized individuals. This is of particular interest in cheetahs (Acinonyx jubatus), which in captivity are known to suffer from chronic diseases that may be associated with hypertension and which often require immobilization for transport or veterinary treatment. Invasive testing methods are considered the gold standard but are not practical in many settings. Consequently, it is important to evaluate the use of noninvasive methods in this species. Measurements for systolic, diastolic, and mean arterial pressure obtained using high-definition oscillometry (HDO) at the coccygeal artery were compared to simultaneous direct measurements obtained via catheterization of the femoral or dorsal pedal artery in eight anesthetized captive cheetahs during nine anesthetic events. Overall, HDO and direct measurements agreed most closely for mean arterial pressure, and the poorest agreement was observed for systolic pressure. There was a tendency for low diastolic pressures to be underestimated and for high diastolic pressures to be overestimated. Across all three parameters, HDO measurements from the tail overestimated directly measured pressures in the femoral artery and underestimated those in the dorsal pedal artery. HDO agreed most closely with directly measured dorsal pedal pressures. Mean arterial pressure showed the greatest precision (standard deviation of 10.2 mm Hg) and lowest bias (-1.2 mm Hg), with 75.9% of readings within 10 mm Hg of the direct dorsal pedal pressure. Agreement with systolic pressure was hindered by a high bias (-10.4 mm Hg), but if a correction factor of +10 mm Hg was applied to all systolic measurements, agreement was improved and 65.7% of readings were within 10 mm Hg of the direct pressure. When compared to criteria defined by the American College of Veterinary Internal Medicine for validation of blood pressure devices, results were favorable, but a limited sample size prevented formal validation. PMID- 26352955 TI - CRYOPRESERVATION OF ONAGER (EQUUS HEMIONUS ONAGER) EPIDIDYMAL SPERMATOZOA. AB - Genetic diversity is a primary component of adaptive evolution, and its loss or reduction can decrease the long-term survival probability of populations. Utilization of cryopreserved semen may be considered a perfect tool to improve genetic diversity, reduce inbreeding, and avoid animal translocation for breeding. The present study aimed at finding a reliable epididymal sperm freezing protocol for the critically endangered onager (Equus hemionus onager). Six testicles from three animals were processed postmortem. The effects of two transportation temperatures (22 degrees C and 4 degrees C; testicles submerged in saline), two cryopreservation techniques (conventional liquid nitrogen vapor freezing in straws and directional freezing in 8-ml HollowTubes(TM)), and two postthaw incubation temperatures (22 degrees C and 37 degrees C; evaluated after 0.5, 1, 2, and 3 hr) were tested in a 2*2*2 experimental design. Sperm samples were evaluated for motility, viability, acrosome integrity, and sperm morphology. The resulting optimal freezing protocol includes transportation of testicles at 4 degrees C, cryopreservation by directional freezing, and, if needed, postthaw incubation at 22 degrees C. With this combination of transportation temperature and cryopreservation technique, the authors obtained the following postthaw values normalized to prefreezing values: 60.3+/-8.8% motility, 60.7+/-13.3% viability, 75.3+/-9.5% acrosome integrity, and 94.7+/-2.9% normal morphology (excluding defects due to the epididymal origin of the sperm). After incubation at 22 degrees C, motility values for the above combination were 40+/-5.7%, 30.3+/ 5.2%, 28.3+/-4.4%, and 16.7+/-4.4% for 0.5, 1, 2, and 3 hr, respectively. In conclusion, with this protocol, good quality semen can be stored for future use in artificial inseminations when and where needed. PMID- 26352956 TI - PREVALENCE OF VALVULAR REGURGITATIONS IN CLINICALLY HEALTHY CAPTIVE LEOPARDS AND CHEETAHS: A PROSPECTIVE STUDY FROM THE WILDLIFE CARDIOLOGY (WLC) GROUP (2008 2013). AB - The purpose of this prospective study was to evaluate transthoracic echocardiograms from clinically healthy large felids for the presence of valvular regurgitations (VR). Physiologic VR commonly occur in normal dogs and cats, but the percentage of large felids with VR has not been previously reported. During a 5-yr study period (2008-2013), 28 healthy animals were evaluated under general anesthesia: 16 cheetahs (Acinonyx jubatus soemmeringuii) with a mean age of 1.5+/ 0.8 yr (range 0.7-3.5 yr), 5 Amur leopards (Panthera pardus orientalis), 1 snow leopard (Uncia uncia), and 6 clouded leopards (Neofelis nebulosa). For this study, all the leopards were gathered in one so-called "leopards group" with a mean age of 2.8+/-3.4 yr (range 0.3-10.7 yr). All valves observed in each view were examined for evidence of regurgitant jets and turbulent blood flow using the color-flow Doppler mode. Valves were also examined for structural changes. Mitral valve and aortic cusp abnormalities were considered to be of congenital origin. Mitral valve lesions led to mitral insufficiency in all the felids. Aortic cusp abnormalities led to aortic regurgitation in 94% of the cheetahs and 67% of the leopards. Leopards showed a predominance of early systolic mitral regurgitations, whereas all the mitral regurgitation jets in cheetahs were holosystolic. Tricuspid regurgitation was found in 81% of the cheetahs and in 50% of the leopards, whereas pulmonic regurgitation was detected in 44% of the cheetahs and 33% of the leopards. Interestingly, none of these tricuspid and pulmonic regurgitations were associated with two-dimensional structural valve abnormalities, thus suggesting their physiologic origin, as described in humans, cats, and dogs. In conclusion, subclinical valvular diseases are common in apparently healthy leopards and cheetahs. Longitudinal follow-up of affected animals is therefore required to assess their clinical outcome. PMID- 26352957 TI - ANESTHETIC INDUCTION AND RECOVERY PARAMETERS IN BEARDED DRAGONS (POGONA VITTICEPS): COMPARISON OF ISOFLURANE DELIVERED IN 100% OXYGEN VERSUS 21% OXYGEN. AB - Inland bearded dragons (Pogona vitticeps, n=6) were anesthetized for 1 hr using isoflurane in either 100% oxygen or 21% oxygen (FI 21; medical-grade room air). Parameters of anesthetic depth were recorded throughout both induction and recovery by an observer blinded to the fraction of inspired oxygen (FiO2), including the loss and return of withdrawal and righting reflexes, muscle tone, ability to intubate or extubate, and return to spontaneous respiration. Physiologic data were recorded every 5 min throughout the anesthetic procedures, including heart rate, body temperature, end-tidal CO2, hemoglobin oxygen saturation (SpO2), and percent expired isoflurane. Lizards were subjected to application of a noxious stimulus (needle stick) at 0, 30, and 60 min, and responses recorded. Following a minimum 7-day washout period, the experiment was repeated with each lizard subjected to the other protocol in a randomized, complete crossover design. The only statistically significant difference was a lower mean SpO2 in the group inspiring 21% oxygen (P<0.0020). No statistically significant differences were detected in any parameters during induction or recovery; however, all values were uniformly shorter for the FI 21 group, indicating a possible clinically significant difference. A larger sample size may have detected statistically significant differences. Further studies are needed to evaluate these effects in other reptile species and with the concurrent use of injectable anesthetic and analgesic drugs. PMID- 26352958 TI - DISEASE RISK ANALYSIS--A TOOL FOR POLICY MAKING WHEN EVIDENCE IS LACKING: IMPORT OF RABIES-SUSCEPTIBLE ZOO MAMMALS AS A MODEL. AB - Disease control management relies on the development of policy supported by an evidence base. The evidence base for disease in zoo animals is often absent or incomplete. Resources for disease research in these species are limited, and so in order to develop effective policies, novel approaches to extrapolating knowledge and dealing with uncertainty need to be developed. This article demonstrates how qualitative risk analysis techniques can be used to aid decision making in circumstances in which there is a lack of specific evidence using the import of rabies-susceptible zoo mammals into the United Kingdom as a model. PMID- 26352959 TI - PHARMACOKINETIC PROPERTIES OF A SINGLE ADMINISTRATION OF ORAL GABAPENTIN IN THE GREAT HORNED OWL (BUBO VIRGINIANUS). AB - Gabapentin (1-[aminomethyl] cyclohexane acetic acid) is a gamma-aminobutyric acid analogue that has been shown to be efficacious for neuropathic pain control in humans. Plasma gabapentin concentrations >2 MUg/ml are considered effective in treating epilepsy in humans and are suggested to provide analgesia for neuropathic pain. This study investigated the pharmacokinetics of a single oral dose of gabapentin suspension (11 mg/kg) in great horned owls ( Bubo virginianus ). Plasma gabapentin concentrations were determined in six healthy birds for 48 hr using high-performance liquid chromatography with mass spectrometric detection. Plasma gabapentin concentrations were estimated by noncompartmental pharmacokinetic analysis. The harmonic mean (+/-SD) maximum concentration (Cmax), time to maximum concentration (Tmax), and elimination half-life (tv2lambdaZ) for gabapentin (11 mg/kg) were 6.17+/-0.83 MUg/ml, 51.43+/-5.66 min, and 264.60+/ 69.35 min, respectively. In this study, plasma gabapentin concentrations were maintained above 2 MUg/ml for 528 min (8.8 hr), suggesting that gabapentin administered orally every 8 hr may be appropriate in great horned owls. PMID- 26352960 TI - SURGICAL TREATMENT OF OSTEOARTHRITIS IN HARBOR SEALS (PHOCA VITULINA). AB - In 2012, 543 harbor seals (Phoca vitulina) and 124 grey seals (Halichoerus grypus) were admitted to the Seal Rehabilitation and Research Centre in Pieterburen, The Netherlands. In 19 seals (3%), signs of infection in a hind flipper were observed. Initial treatment consisting of antibiotics and anti inflammatory drugs resolved the symptoms in 15 animals. In four harbor seals, estimated to be 3 to 4 mo old, a necrotizing infection developed that resulted in osteoarthritis of the tarsus or tibiotarsal joint or both. Bacterial culture revealed the presence of polymicrobial infection in three of the four animals. Treatment consisted of amputation of the hind flipper under general anesthesia combined with tumescent anesthesia in the operation field. Amputations were done at the diaphysis of the tibia and fibula. After resecting these bones, the flipper was discarded, leaving a good muscle-skin cuff to cover the edges of the bones and close the skin without tension. The estimated blood loss varied between <50 to 150 ml. Healing was uneventful, and both antibiotics and analgesics were gradually reduced according to the individual response. The seals did not show any functional impairment 1 mo postoperatively. After release to the sea, scrutinous revision of all radiographs showed signs of osteomyelitis in at least one animal in the proximal part of the tibia, also present preoperatively. It is concluded that tumescent anesthesia in seals may reduce perioperative blood loss and that a lower leg amputation is a surgically easy and clean approach for the treatment of osteoarthritis of the hind flipper of seals, giving good functional results (diving, catching fish, exiting a pool, and moving on land). PMID- 26352961 TI - FATAL SUPPURATIVE INFLAMMATION IN DAURIAN PIKAS (OCHOTONA DAUURICA) NATURALLY INFECTED WITH CASTELLANIELLA GINSENGISOLI-LIKE BACTERIA. AB - Fifteen Daurian pika (Ochotona dauurica) were introduced to a zoological collection in December 2011 as founders for a planned breeding colony. Despite breeding success, the colony shrunk over 37 mo to 11 animals. Mortality in 11 of 46 deceased animals, including wild-caught "founders" and captive-born offspring, was associated with a suppurative inflammation and abscess formation of the spleen, skin, peripheral and internal lymph nodes, liver, lungs, kidney, or a combination of organs. Gram-negative, non-fermenting, rod-shaped bacteria were isolated from the abscesses in all cases. Steiner Chapman silver stain identified rod-shaped bacteria in the abscesses of seven animals. The bacteria were not detected with Gram stain, acid-fast stain, or Grocott silver methenamine stain and was not detectable by periodic acid-Schiff reaction. In two cases, including the index case, the bacteria were presumptively identified as Ralstonia pickettii on the basis of conventional biochemical characterization. The bacteria in the other cases were not further classifiable with conventional methods. Matrix assisted laser desorption/ionization time of flight mass spectrometry and 16s rDNA gene sequencing resulted in identification to the genus level as Castellaniella in 10 of 12 cases. Comparative 16S rDNA gene sequence analysis showed that these isolates and Castellaniella ginsengisoli Strain DCY36T were 99% similar. Castellaniella ginsengisoli, a gram-negative bacterium isolated from soil of a ginseng field in South Korea, has not previously been associated with disease in animals or humans. It is uncertain how the bacterium was introduced to the Daurian pika colony or how it spread. PMID- 26352962 TI - HYPERCALCEMIA AND METASTATIC MINERALIZATION INVOLVING FOOTPADS IN ROCK HYRAXES (PROCAVIA CAPENSIS). AB - Three rock hyraxes (Procavia capensis) maintained in a zoological collection had chronic hypercalcemia and azotemia. In addition, all animals displayed signs of lameness due to footpad lesions that were histologically characterized as marked metastatic mineralization with granulomatous inflammation, reminiscent of calcinosis circumscripta. Although the animals were managed with aggressive fluid therapy, calciuresis, and dietary modification, all were eventually humanely euthanized due to the severity of their footpad lesions and/or progression of renal disease. Metastatic mineralization was also noted in other soft tissues among the three cases, including the stomach, colon, lung, vascular wall, ovary, and kidney. Varying degrees of interstitial nephritis were confirmed on postmortem examination, and in the absence of other causes for hypercalcemia, metastatic mineralization was presumably the consequence renal dysfunction. The renal pathway is the primary mode of calcium excretion in the rock hyrax. In renal dysfunction, hypercalcemia may develop secondary to decreased calcium excretion. Footpad mineralization is an uncommon sequel to renal dysfunction in domestic animals but has not been reported in rock hyraxes. A retrospective review of mortality data in this collection revealed a notable prevalence of renal lesions, including two additional animals with metastatic mineralization and renal dysfunction. Expanding knowledge of renal diseases will further guide preventative and clinical measures, including screening for metastatic mineralization and therapeutic trials for management of hypercalcemia and calcium mineral deposition in the footpads and other soft tissues. PMID- 26352963 TI - SUCCESSFUL DIAGNOSIS AND TREATMENT OF BILATERAL PERINEAL HERNIAS IN A SKUNK (MEPHITIS MEPHITIS). AB - This brief communication describes the diagnosis and surgical treatment of bilateral perineal hernias in a 1-yr-old, intact female, striped skunk (Mephitis mephitis) that was evaluated for chronic intermittent constipation, following early age, bilateral anal sacculectomy for descenting. Complete blood count and biochemistry results were within the reference ranges. Diagnosis was based on history, physical exam, clinical signs, and diagnostic imaging. A two-stage surgical approach for treatment was performed. First, colopexy and cystopexy were performed via celiotomy, which was followed by unilateral perineal herniorrhaphy by using an internal obturator muscle flap augmented with porcine small intestinal submucosa biomaterial. Long-term resolution of clinical signs was achieved without evidence of recurrence. This is the first description of bilateral perineal hernia in a skunk following routine anal sacculectomy for descenting. PMID- 26352964 TI - T-CELL LYMPHOCYTIC LEUKEMIA IN A FALLOW DEER (DAMA DAMA). AB - A 17-yr-old female fallow deer presented with ataxia, inappetence, decreased fecal output, and decreased mentation. A complete blood count demonstrated leukocytosis (24.1*10(3)/MUl, n=1.16-7.38*10(3)/MUl), characterized by lymphocytosis (22.89*10(3)/MUl, n=0.18-3.65*10(3)/MUl), anemia (packed cell volume 20%, n=29.0-55.8%), decreased red blood cell count (4.1*10(3)/MUl, n=6.86 14.72*10(3)/MUl), and decreased hemoglobin (7.5 g/dl, n=9.4-19.2 g/dl). Numerous mature, well-differentiated lymphocytes were noted on the blood film. Despite treatment and clinical improvement, the decision was made to euthanize the deer. Histopathology identified a monomorphic population of CD3 positive, CD79a negative small lymphocytes replacing most of the hematopoietic tissue in the bone marrow without evidence of tissue invasion. Results of viral screening were negative. PMID- 26352965 TI - HISTOLOGIC, IMMUNOHISTOCHEMICAL, AND ELECTRON MICROSCOPIC CHARACTERIZATION OF A MALIGNANT IRIDOPHOROMA IN A DWARF BEARDED DRAGON (POGONA HENRYLAWSONI). AB - A dwarf bearded dragon (Pogona henrylawsoni) was presented with a white subcutaneous mandibular mass and multiple nodules in the oral mucosa, heart, liver, kidney, intestine, and visceral fat. Histologically, the tumor consisted of densely packed spindle-shaped cells with brow intracytoplasmic pigment that exhibited white-blue birefringence with polarized light. Immunohistochemical staining was negative for S-100 and weakly positive with melan A. Electron microscopic examination revealed cytoplasmic irregular and oblong empty spaces, laminated and often arranged into short stacks, compatible with reflecting platelet profiles typically seen in iridophores. However, in unstained ultrathin sections, electron-dense crystalline material was present, which filled the empty spaces described for stained sections before. Based on histology, immunohistochemistry, and biologic behavior, a malignant iridophoroma was diagnosed. To the authors' knowledge, iridophoromas in lizards have rarely been characterized by using electronic microscopy. Moreover, this is the first description of an iridophoroma in a dwarf bearded dragon. PMID- 26352966 TI - YERSINIA PSEUDOTUBERCULOSIS, SEROGROUP O:1A, INFECTION IN TWO AMAZON PARROTS (AMAZONA AESTIVA AND AMAZONA ORATRIX) WITH HEPATIC HEMOSIDEROSIS. AB - Necropsies were conducted on a female blue-fronted Amazon (Amazona aestiva) and a female yellow-headed Amazon (Amazona oratrix) that died after depression, ruffled feathers, diarrhea, and biliverdin in the urine. Gross and microscopic examinations revealed multifocal necrosis in the liver, spleen, lungs, kidneys, intestines, and heart caused by acute bacteremia. Yersinia pseudotuberculosis, serogroup O:1a, was isolated by culturing from the visceral lesions in the liver, intestines, and spleen. Virulence gene analysis showed the presence of the inv gene and the complete pathogenicity island: IS100, psn, yptE, irp1, irp2 ybtP ybtQ, ybtX-ybtS, and int asnT-Int. Histopathologic findings and chemical analysis also demonstrated hepatic hemosiderosis. As has been demonstrated in other species, hemosiderosis may predispose Amazona spp. to systemic infection with Y. pseudotuberculosis after enteric disease. PMID- 26352967 TI - MITE INFECTION IN A MASKED PALM CIVET (PAGUMA LARVATA) TREATED BY SELAMECTIN (STRONGHOLD(r), PFIZER LTD.). AB - The masked palm civet (Paguma larvata) is a small Asian mammal (order Carnivora, family Viverridae) uncommon in Italy. Limited information is available about management and sanitary maintenance in captivity. A 4-mo-old masked palm civet presented with pruritus, itch, scratching, and disorexia. On physical examination, alopecia and crusts were detected on the ventral and lateral trunk, tail, legs, and lips. Skin scrapings and cytology revealed Notoedres spp. and bacterial infection. On histopathology, parasitic dermatitis was observed with the presence of a Sarcoptidae mite and Demodex spp. Selamectin spot-on (15 mg/kg every 2 wk, three applications) and marbofloxacin per os (2.5 mg/kg once daily for 2 wk) were administered, and the animal recovered in 1 mo. With the good response to this therapy, a notoedric mange was thought to be the main problem. This is the first report about the use of selamectin to treat a mite infection in masked palm civet. PMID- 26352968 TI - SMALL INTESTINAL ADENOCARCINOMA WITH CARCINOMATOSIS IN A SWIFT FOX (VULPES VELOX). AB - A 7-yr-old, intact, female swift fox (Vulpes velox) presented to the Veterinary Health Center at Kansas State University with a history of chronic weight loss, lethargy, inappetence, and myiasis. On physical examination, a firm mass was palpated in the mid- to cranial abdomen. The fox was euthanatized as a result of the grave prognosis. Gross necropsy and histologic findings included a small intestinal adenocarcinoma with diffuse transperitoneal spread throughout the abdominal cavity (carcinomatosis). To the authors' knowledge, this is the first report of intestinal adenocarcinoma with carcinomatosis in a swift fox. PMID- 26352969 TI - CLINICAL COPPER TOXICOSIS IN A LARGE MIXED GROUP OF MARINE INVERTEBRATES. AB - A mixed group of 441 marine invertebrates was collected in Southern California. After a large mortality event, numerous water quality parameters were evaluated. Copper was present at 33 MUg/L, which is below the documented toxic level. No other toxins were identified. To investigate whether copper was the etiology for the mass mortality, purple sea urchins, Strongylocentrotus purpuratus , were used as sentinel species, as they were the most severely affected during the mortality event. Purple sea urchins were placed in multiple test systems of varying copper concentrations and died in periods of time proportionate to copper concentrations. Clinical signs, disease progression, and pathologic lesions were similar between test systems and the original mortality event. Copper caused disease and death in purple sea urchins at concentrations from 15 to 50 MUg/L. The source of the copper toxicity was identified as sand filters contaminated by brass pump components. PMID- 26352970 TI - ACUTE CLINICAL LEPTOSPIROSIS (GRIPPOTYPHOSA SEROVAR) IN AN ADULT DROMEDARY CAMEL (CAMELUS DROMEDARIUS). AB - A 9-yr-old castrated male dromedary camel (Camelus dromedarius) presented with lethargy and partial anorexia. A diagnostic examination revealed fever, and further workup revealed a neutrophilia, hyperfibrinogenemia, renal azotemia, and a rapid onset of a high Leptospira antibody titer during the acute clinical period (Grippotyphosa serovar). The camel responded clinically to antimicrobial treatment with ceftiofur crystalline free acid injections, but renal azotemia persisted, presumably secondary to chronic renal damage. Subsequent Leptospira polymerase chain reaction testing on urine samples obtained over the following 4 mo revealed no evidence of urinary shedding, so a persistent infection was unlikely. Although often mentioned as a potential cause of reproductive loss, well-documented case reports of clinical leptospirosis in camelids are very rare. In this case, native wildlife contamination of a small watering hole is suspected to have been the source of infection. In response to this experience, the camel and two conspecifics were prescribed a vaccination regimen using an inactivated pentavalent Leptospira vaccine licensed for cattle. PMID- 26352971 TI - DIAGNOSIS AND SURGICAL TREATMENT OF A COMPLEX ANGULAR HIND LIMB DEFORMITY IN A SERVAL (FELIS SERVAL). AB - A 2-yr-old neutered male pet serval (Felis serval) was presented for progressive hind limb lameness that started at 6 mo of age. Previous therapy included only nutritional supplementation. Direct and video gait analysis confirmed bilateral hind limb lameness, more severe on the right. Physical examination and radiography revealed a multifocal complex bilateral angular deformity with a significant rotational component. A right tibial corrective osteotomy was followed by internal rotation and stabilization with a 2.7-mm eight-hole locking compression plate and locking screws. Other deformities were not corrected. Clinical improvement was noted immediately and has been maintained over the 16-mo follow-up. PMID- 26352972 TI - FUNGAL OSTEOMYELITIS IN TWO BUFFLEHEAD DUCKLINGS (BUCEPHALA ALBEOLA). AB - Over a 25-mo span from a single zoologic collection, two bufflehead ducklings (Bucephala albeola) presented with pelvic limb paresis and were euthanized. On postmortem examination, the first duckling had intralesional fungal hyphae consistent with Aspergillus sp. in the spinal vertebrae and within pulmonary granulomas. In the second duckling, evidence of a thoracic spinal lesion was detected antemortem by using thermographic imaging. At postmortem examination, fungal hyphae consistent with Mucor sp. were found within the vertebrae. Although fungal infections of the respiratory system are commonly reported in waterfowl, infections that involve the spinal cord and vertebrae are unusual. These cases highlight the importance of consideration of axial skeleton fungal disease in neurologic presentations and the use of thermography for noninvasive diagnostic screening. PMID- 26352973 TI - USE OF CORTICAL BONE FENESTRATION, AUTOGENOUS FREE SKIN GRAFT, AND THERMOGRAPHY FOR WOUND TREATMENT AND MONITORING IN A RED WOLF (CANIS RUFUS GREGORYI). AB - A 2-yr-old female red wolf (Canis rufus gregoryi) sustained a degloving injury to the left thoracic limb while in a display habitat. Initial attempts to resolve the extensive wound by using conservative measures were unsuccessful. Subsequent treatment using a free skin graft consisted first of establishment of an adequate granulation bed via cortical bone fenestration. After establishment of a healthy granulation bed was achieved, free skin graft was harvested and transposed over the bed. To monitor viability and incorporation of the graft, serial thermographic imaging was performed. Thermography noninvasively detects radiant heat patterns and can be used to assess vascularization of tissue, potentially allowing early detection of graft failure. In this case, thermography documented successful graft attachment. PMID- 26352974 TI - A CASE OF TRYCHOPHYTON RUBRUM DERMATOPHYTOSIS IN A PATAGONIAN SEA LION (OTARIA BYRONIA). AB - A 23-yr old female Patagonian sea lion (Otaria byronia) presented multifocal to coalescing and ulcerative skin lesions on the lumbar region. Skin scrapings were collected and a microscopic examination was conducted followed by a fungal culture that revealed a Trychophyton rubrum infection, an anthropophilic dermatophytosis agent. Oral terbinafine and topical eniconazole were used as a treatment for a period of 75 days and complete recovery was achieved. Epidemiological analysis revealed a dermatophytosis case in one of the carnivore section keepers a few weeks before the lesions were diagnosed in the sea lion. PMID- 26352975 TI - MEDULLOBLASTOMA IN A GRIZZLY BEAR (URSUS ARCTOS HORRIBLIS). AB - A 3-yr-old female spayed grizzly bear (Ursus arctos horribilis) was evaluated for seizure activity along with lethargy, inappetence, dull mentation, and aggressive behavior. Magnetic resonance (MR) examination of the brain revealed a contrast enhanced right cerebellar mass with multifocal smaller nodules located in the left cerebellum, thalamus, hippocampus, and cerebrum with resultant obstructive hydrocephalus. Cerebrospinal fluid analysis revealed mild mononuclear pleocytosis, with differentials including inflammatory versus neoplastic processes. Blood and cerebrospinal fluid were also submitted for polymerase chain reaction and agar gel immunodiffusion to rule out infectious causes of meningitis/encephalitis. While awaiting these results, the bear was placed on steroid and antibiotic therapy. Over the next week, the bear deteriorated; she died 1 wk after MR. A complete postmortem examination, including immunohistochemisty, revealed the cerebellar mass to be a medulloblastoma. This is the only case report, to the authors' knowledge, describing a medulloblastoma in a grizzly bear. PMID- 26352976 TI - BILATERALLY SYMMETRICAL ORAL AMELANOTIC MELANOMA IN A BOA CONSTRICTOR (BOA CONSTRICTOR CONSTRICTOR). AB - A 17-yr-old boa constrictor (Boa constrictor constrictor) presented initially with diffuse gingival swelling, loose teeth, and loss of body condition. Examination under anesthesia revealed two firm pink masses within the oral cavity. The largest mass was removed for biopsy. Histopathology and Melan-A positive immunohistochemistry labeling confirmed a diagnosis of amelanotic melanoma. Secondary stomatitis was treated with antibiotics to improve quality of life, but the snake's condition deteriorated quickly over the next 2 mo. Euthanasia was elected and a gross postmortem examination was performed. Gross postmortem examination and histopathology results demonstrated that the neoplastic cells had spread in an unusual symmetrical pattern along all four dental arcades: the right and left sides of both the mandible and maxilla. Histopathology confirmed metastasis throughout the liver and spleen, despite the lack of gross lesions. PMID- 26352977 TI - "TERATOCARCINOMATOSIS" IN AN EMU (DROMAIUS NOVAEHOLLANDIAE). AB - An adult female emu (Dromaius novaehollandiae) with no previous abnormal clinical signs was found dead in its stall. A postmortem examination revealed carcinomatosis of unknown origin. Histopathology identified the masses as teratomas with malignant transformation by the presence of poorly differentiated tissue and dissemination throughout the coelomic cavity. We propose a new term, "teratocarcinomatosis," for this finding. This is the first case of a reproductive tumor described in an emu and the first case of such marked spread of malignant teratomas in a bird. PMID- 26352978 TI - TISSUE ENZYME ACTIVITIES IN KEMP'S RIDLEY TURTLES (LEPIDOCHELYS KEMPII). AB - This study determined the tissue distribution and activities of eight enzymes in 13 juvenile Kemp's ridley turtles (Lepidochelys kempii) that died after stranding. Samples from the liver, kidney, skeletal muscle, cardiac muscle, pancreas, lung, small intestine, and spleen were evaluated for activities of alanine aminotransferase (ALT), alkaline phosphatase (ALP), amylase, aspartate aminotransferase (AST), creatine kinase (CK), gamma-glutamyl transferase (GGT), lactate dehydrogenase (LDH), and lipase. AST, CK, and LDH activities were highest in cardiac and skeletal muscle but were also found in all other tissues. Amylase and lipase activities were highest in the pancreas and low in all other tissues. ALP activity was highest in the lung. ALT activity was highest in liver, kidney, and cardiac muscle, and GGT activity was highest in the kidney, but activities of these enzymes were low in all tissues. These data may assist clinicians in interpretation of plasma enzyme activities of Kemp's ridley turtles. PMID- 26352979 TI - TREATMENT OF CHRONIC HERPESVIRAL DERMATITIS IN A CAPTIVE CHEETAH (ACINONYX JUBATUS) IN NAMIBIA. AB - A 9-yr-old male cheetah (Acinonyx jubatus) housed at the Cheetah Conservation Fund in Namibia developed cutaneous lesions consisting of alopecia, erythema, ulceration, and crusting on the left fore and hind limbs. Histopathology of skin biopsies in conjunction with indirect fluorescent antibody and polymerase chain reaction testing confirmed a diagnosis of feline herpesvirus-1 dermatitis; microbial culture indicated secondary bacterial infection. Therapy included targeted systemic antimicrobial and antiviral treatment, topical medications, and repeated cryotherapy. Lesions exhibited varying degrees of clinical improvement but, overall, progressed in extent, size, and severity during the subsequent 2.5 yr of intense treatment. The cheetah was ultimately euthanized due to a guarded prognosis and concerns about poor quality of life. Potential factors initiating or contributing (or both) to the severity and nonhealing nature of the cutaneous lesions include chronic unidentified stress, altered immune system function, and other environmental influences. PMID- 26352980 TI - APHAKIC PHACOEMULSIFICATION AND AUTOMATED ANTERIOR VITRECTOMY, AND POSTRETURN MONITORING OF A REHABILITATED HARBOR SEAL (PHOCA VITULINA RICHARDSI) PUP. AB - A female harbor seal pup rescued along the coast of San Diego on 13 June 2012 was diagnosed with bilateral mature cataracts, apparently congenital, in association with vitreal herniation in the anterior chamber of each eye. The cataracts were surgically removed on 1 August 2012 with single-port aphakic phacoemulsification and automated anterior vitrectomy. Postoperative monitoring during the next several weeks indicated that vision had been functionally repaired and that she could visually orient to and capture live fish in three different environments and in the presence of other animals. Consequently, we equipped the seal with a satellite-linked radio transmitter and returned her to the Pacific Ocean on 21 November 2012, and then monitored her movements until radio contact ended on 2 March 2013. She remained along the San Diego coast from 21 November until 5 December 2012 when she relocated to the Coronado Islands and remained there until 26 December. She then traveled directly to San Clemente Island and remained foraging in the near-shore kelp beds there through 2 March 2013, when radio contact ended. To our knowledge, this is the first published report of cataract treatment in a marine mammal using high-frequency ultrasound to emulsify the lenses followed by suction removal of the emulsified microfragments (i.e., phacoemulsification). Moreover, the rapid postoperative recovery of the seal and its quick acclimation, orientation, navigation, and foraging in marine habitats after return to the Pacific Ocean indicates that these surgical procedures can be safe and effective treatments for cataracts in seals, with substantially reduced postsurgical complications relative to other types of lens fragmentation and removal procedures. PMID- 26352981 TI - MANAGEMENT OF ACUTE RENAL FAILURE WITH DELAYED HYPERCALCEMIA SECONDARY TO SARCOCYSTIS NEURONA-INDUCED MYOSITIS AND RHABDOMYOLYSIS IN A CALIFORNIA SEA LION (ZALOPHUS CALIFORNIANUS). AB - A 3-yr-old captive-born California sea lion (Zalophus californianus) developed Sarcocystis neurona-induced myositis and rhabdomyolysis that led to acute renal failure. The sea lion was successfully managed with fluid therapy, antiprotozoals, antibiotics, anti-inflammatories, antiemetics, gastroprotectants, and diuretics, but developed severe delayed hypercalcemia, a syndrome identified in humans after traumatic or exertion-induced rhabdomyolysis. Treatment with calcitonin was added to the management, and the individual recovered fully. The case emphasizes that animals with rhabdomyolysis-induced renal failure risk developing delayed hypercalcemia, which may be life threatening, and calcium levels should be closely monitored past the resolution of renal failure. PMID- 26352982 TI - CLINICAL CHALLENGE. Diagnosis: Mesocestoides spp. PMID- 26352985 TI - Anatomy of the Enigmatic Reptile Elachistosuchus huenei Janensch, 1949 (Reptilia: Diapsida) from the Upper Triassic of Germany and Its Relevance for the Origin of Sauria. AB - The holotype and only known specimen of the enigmatic small reptile Elachistosuchus huenei Janensch, 1949 from the Upper Triassic (Norian) Arnstadt Formation of Saxony-Anhalt (Germany) is redescribed using MUCT scans of the material. This re-examination revealed new information on the morphology of this taxon, including previously unknown parts of the skeleton such as the palate, braincase, and shoulder girdle. Elachistosuchus is diagnosed especially by the presence of the posterolateral process of the frontal, the extension of the maxillary tooth row to the posterior margin of the orbit, the free posterior process of the jugal, and the notched anterior margin of the interclavicle. Phylogenetic analyses using two recently published character-taxon matrices recovered conflicting results for the phylogenetic position of Elachistosuchus either as an archosauromorph, as a lepidosauromorph or as a more basal, non saurian diapsid. These different placements highlight the need of a thorough revision of critical taxa and new character sets used for inferring neodiapsid relationships. PMID- 26352986 TI - Atrial SERCA2a Overexpression Has No Affect on Cardiac Alternans but Promotes Arrhythmogenic SR Ca2+ Triggers. AB - BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia in humans, yet; treatment has remained sub-optimal due to poor understanding of the underlying mechanisms. Cardiac alternans precede AF episodes, suggesting an important arrhythmia substrate. Recently, we demonstrated ventricular SERCA2a overexpression suppresses cardiac alternans and arrhythmias. Therefore, we hypothesized that atrial SERCA2a overexpression will decrease cardiac alternans and arrhythmias. METHODS: Adult rat isolated atrial myocytes where divided into three treatment groups 1) Control, 2) SERCA2a overexpression (Ad.SERCA2a) and 3) SERCA2a inhibition (Thapsigargin, 1MUm). Intracellular Ca2+ was measured using Indo-1AM and Ca2+ alternans (Ca-ALT) was induced with a standard ramp pacing protocol. RESULTS: As predicted, SR Ca2+ reuptake was enhanced with SERCA2a overexpression (p< 0.05) and reduced with SERCA2a inhibition (p<0.05). Surprisingly, there was no difference in susceptibility to Ca-ALT with either SERCA2a overexpression or inhibition when compared to controls (p = 0.73). In contrast, SERCA2a overexpression resulted in increased premature SR Ca2+ (SCR) release compared to control myocytes (28% and 0%, p < 0.05) and concomitant increase in SR Ca2+ load (p<0.05). Based on these observations we tested in-vivo atrial arrhythmia inducibility in control and Ad.SERCA2a animals using an esophageal atrial burst pacing protocol. There were no inducible atrial arrhythmias in Ad.GFP (n = 4) animals though 20% of Ad.SERCA2a (n = 5) animals had inducible atrial arrhythmias (p = 0.20). CONCLUSIONS: Our findings suggest that unlike the ventricle, SERCA2a is not a key regulator of cardiac alternans in the atrium. Importantly, SERCA2a overexpression in atrial myocytes can increase SCR, which may be arrhythmogenic. PMID- 26352987 TI - High-Resolution Genomic Analysis of Cribriform Neuroepithelial Tumors of the Central Nervous System. AB - Cribriform neuroepithelial tumors (CRINET) are one of several recently characterized entities in the broad spectrum of solid tumors with SMARCB1-INI1 loss. This neoplasm seems to be exceedingly rare and displays unique neuropathologic and clinical features. To date, only a few cases of CRINET have been characterized from a molecular point of view. In this study, we investigated the molecular features of 3 cases of CRINET using multiplex ligation-dependent probe amplification and molecular inversion profiling approaches. Along with mutations and deletions of SMARCB1-INI1, molecular inversion profiling analysis revealed a stable genomic profile without significant large chromosomal changes. Focal alterations (gains) were observed in individual cases at chromosomes 4q12 (PDGFRA), 12q15 (MDM2), 7p15.1 (NPY), and 18q11.2 (CDH2). Genomic Identification of Significant Targets in Cancer analysis highlighted focal alterations, including gains at chromosomes 16q23.2 (MAF), 17q23 (AXIN2), and 8p12 (ADAM3A). No cases showed BRAF(V600E) or CTNNB1 mutations. These data indicate that CRINET present stable genetic features and lack alterations commonly identified in other pediatric brain tumors. Further studies are required to determine whether specific alterations and specific signaling pathways, in addition to SMARCB1 INI1, may be implicated in the biology of this rare tumor and whether there are additional molecular similarities between CRINET and atypical teratoid/rhabdoid tumors. PMID- 26352989 TI - A Cluster of CNS Infections Due to B. cereus in the Setting of Acute Myeloid Leukemia: Neuropathology in 5 Patients. AB - Bacillus cereus typically causes a self-limited foodborne gastrointestinal (GI) illness. Severe invasive infection occurs rarely, mainly among immunocompromised hosts. We describe a cluster of B. cereus infections among 5 patients with acute myeloid leukemia and chemotherapy-induced neutropenia. The initial case presented with occipital lobe abscess and was found on biopsy to have organisms consistent with Bacillus species. Within 1 week, a second patient died of fulminant brain swelling and hemorrhage. Neuropathologic autopsy and culture revealed B. cereus; hospital infection control and public health officials were notified. Three more patients died within the subsequent 9 months (2 patients had rapid massive hemorrhage and many bacilli reminiscent of Bacillus anthracis infection, and 1 patient had sparse bacilli, petechial hemorrhages, and border zone infarcts). Blood cultures yielded positive results in 3 of 5 cases. A possible route of infection was hematogenous dissemination via GI mucosal breaches (GI symptoms occurred in 3 of 5 cases, and postmortem GI ulceration was found in 3 of 4 cases). Bacilli were seen in 2 of 3 GI ulcerations. Epidemiologic work-up, including a site visit conducted by the Centers for Disease Control and Prevention, did not identify a clear common source but suggested the possibility of bananas as a food source. Bacillus cereus causes a rapidly progressive, hemorrhagic meningoencephalitis with high mortality among patients with neutropenia. Neuropathologists can play a key role in the detection of outbreaks. PMID- 26352990 TI - Prominent Vascular and Perivascular Eosinophilic Infiltrates Heralding CNS Mycosis Fungoides. AB - Brain parenchymal involvement of mycosis fungoides (MF) is very rare. This study reports a patient with known cutaneous MF (under treatment) who presented with a CNS syndrome and multiple brain lesions. Brain biopsy demonstrated massive eosinophilic infiltrates but no MF cells. Despite treatment, new lesions developed and the patient died. At autopsy, there was massive involvement MF cells, suggesting that the eosinophilic infiltrates presaged the severe involvement of the CNS by MF. PMID- 26352991 TI - Variability in Opioid Equivalence Calculations. AB - OBJECTIVE: Equianalgesic conversion methods are commonly used to switch patients from one opioid to another due to suboptimal pain relief or adverse events. There is no universally accepted opioid conversion method, however, and there is often significant variability between conversion resources. As a result, patients are at risk for undertreated pain and serious adverse events. The purpose of this survey was to compare the equianalgesic conversion estimates between nurse practitioners, pharmacists, and physicians for commonly prescribed opioids. METHODS: A survey form was developed using Survey Monkey. Participation was solicited by providing a link to the survey via social media (e.g., Facebook, Twitter, LinkedIn, etc.) and emailing professional organizations for sharing with their members and followers. Data collected included demographics and estimated morphine equivalents (MEQs) of hydrocodone 80 mg, fentanyl transdermal patches 1,800 mcg (as 75 mcg/hour), methadone 40 mg, oxycodone 120 mg, and hydromorphone 48 mg. Participants were also asked to provide their choice of reference utilized to complete the conversions, including personal knowledge. Descriptive analyses were performed using measures of central tendency. Hypothesis testing was performed using Pearson's chi-squared and Fisher's Exact Test for categorical data and the Kruskal-Wallis equality of populations rank test for continuous data to assess differences between median opioid doses by professional groups. RESULTS: The total number of respondents included in the analysis was 319. Physicians, pharmacists, and nurse practitioners/physician assistants comprised 25.4%, 56.7%, and 16.3%, respectively, of respondents. The overall mean (+/- standard deviation) MEQ doses for fentanyl, hydrocodone, hydromorphone, methadone, and oxycodone were: 176 (+/-117) mg, 88 (+/-42) mg, 192 (+/-55) mg, 193 (+/-201) mg, and 173 (+/-39) mg, respectively. For fentanyl, the mean (+/ standard deviation) MEQ doses were 180 (+/-122) mg, 178 (+/-128) mg, and 157 (+/ 68) mg, for physicians, pharmacists, and nurse practitioners/physician assistants, respectively. For all three groups of clinicians, the median MEQ dose for fentanyl was 150 mg. The mean (+/-standard deviation) MEQ doses of methadone for physicians, pharmacists, and nurse practitioners/physician assistants were: 214 (+/-142) mg, 171 (+/-107) mg, and 185 (+/-129) mg, respectively. The median MEQ dose for methadone was 160 mg for each of the clinician groups. CONCLUSIONS: As evidenced by large standard deviations, there was significant variation in mean opioid conversions to MEQ doses within each profession type, particularly for fentanyl and methadone. The median MEQ doses provided for opioid conversions were the same among each profession. No universal method exists that allows each of the five studied opioids to be accurately and consistently converted to another opioid (i.e., morphine). PMID- 26352988 TI - Primary Meningeal Pleomorphic Xanthoastrocytoma With Anaplastic Features: A Report of 2 Cases, One With BRAF(V600E) Mutation and Clinical Response to the BRAF Inhibitor Dabrafenib. AB - Primary meningeal gliomas are rare tumors composed of a heterogeneous group of neoplasms. We present 2 clinically aggressive cases of primary meningeal pleomorphic xanthoastrocytoma that clinically mimicked meningioma. One case presented in the posterior fossa of a 56-year-old woman; the other centered on the left operculum of a 35-year-old woman. These cases showed many of the classic features of pleomorphic xanthoastrocytoma, except that xanthomatous cells were rare and eosinophilic granular bodies were inconspicuous. Both cases exhibited high proliferative indices and superficially invaded the brain. One case harboring a BRAF mutation disseminated to the thecal sac and showed a clinical response to the targeted BRAF inhibitor dabrafenib. These cases seem to represent an unusual primarily extra-axial presentation of pleomorphic xanthoastrocytoma and may account for at least some of the previously reported cases of primary meningeal glioma and/or glial fibrillary acidic protein-immunoreactive meningioma variants. We suggest that BRAF mutation analysis be considered in all meningeal lesions showing atypical histologic or immunohistochemical profiles, particularly those exhibiting glial differentiation, as a diagnostic aid and possible indication for targeted therapy. PMID- 26352992 TI - Fully Converting Graphite into Graphene Oxide Hydrogels by Preoxidation with Impure Manganese Dioxide. AB - Potassium permanganate (KMnO4) has been proved to be an efficient oxidant for converting graphite into graphite oxide, but its slow diffusion in the interlayer of graphite seriously restricts the production of graphene oxide (GO). Here, we demonstrate that the preoxidation of graphite by impure manganese dioxide (MnO2) in a mixture of concentrated sulfuric acid (H2SO4) and phosphorus pentoxide (P2O5) can efficiently improve the synthesis of GO when KMnO4 is employed as the oxidant. The prepared honey-like GO hydrogels possess a high yield of single layer sheets, large sizes (average lateral size up to 20 MUm), wide ranges of stable dispersion concentrations (from dilute solutions, viscous hydrogels, to dry films), and good conductivity after reduction (~2.9 * 10(4) S/m). The mechanism for the improved synthesis of GO by impure MnO2 was explored. The enhanced exfoliation and oxidation of graphite by oxidative Mn ions (mainly Mn(3+)), which are synergistically produced by the reaction of impure MnO2 with H2SO4 and P2O5, are found to be responsible for the improved synthesis of such GO hydrogels. Particularly, preoxidized graphite (POG) can be partially dispersed in water with sonication, which allows the facile construction of flexible and highly conductive graphene nanosheet film electrodes with excellent electrochemical sensing properties. PMID- 26352993 TI - A Semidefinite Programming Based Search Strategy for Feature Selection with Mutual Information Measure. AB - Feature subset selection, as a special case of the general subset selection problem, has been the topic of a considerable number of studies due to the growing importance of data-mining applications. In the feature subset selection problem there are two main issues that need to be addressed: (i) Finding an appropriate measure function than can be fairly fast and robustly computed for high-dimensional data. (ii) A search strategy to optimize the measure over the subset space in a reasonable amount of time. In this article mutual information between features and class labels is considered to be the measure function. Two series expansions for mutual information are proposed, and it is shown that most heuristic criteria suggested in the literature are truncated approximations of these expansions. It is well-known that searching the whole subset space is an NP hard problem. Here, instead of the conventional sequential search algorithms, we suggest a parallel search strategy based on semidefinite programming (SDP) that can search through the subset space in polynomial time. By exploiting the similarities between the proposed algorithm and an instance of the maximum-cut problem in graph theory, the approximation ratio of this algorithm is derived and is compared with the approximation ratio of the backward elimination method. The experiments show that it can be misleading to judge the quality of a measure solely based on the classification accuracy, without taking the effect of the non optimum search strategy into account. PMID- 26352994 TI - Exploiting Unsupervised and Supervised Constraints for Subspace Clustering. AB - Data in many image and video analysis tasks can be viewed as points drawn from multiple low-dimensional subspaces with each subspace corresponding to one category or class. One basic task for processing such kind of data is to separate the points according to the underlying subspace, referred to as subspace clustering. Extensive studies have been made on this subject, and nearly all of them use unconstrained subspace models, meaning the points can be drawn from everywhere of a subspace, to represent the data. In this paper, we attempt to do subspace clustering based on a constrained subspace assumption that the data is further restricted in the corresponding subspaces, e.g., belonging to a submanifold or satisfying the spatial regularity constraint. This assumption usually describes the real data better, such as differently moving objects in a video scene and face images of different subjects under varying illumination. A unified integer linear programming optimization framework is used to approach subspace clustering, which can be efficiently solved by a branch-and-bound (BB) method. We also show that various kinds of supervised information, such as subspace number, outlier ratio, pairwise constraints, size prior and etc., can be conveniently incorporated into the proposed framework. Experiments on real data show that the proposed method outperforms the state-of-the-art algorithms significantly in clustering accuracy. The effectiveness of the proposed method in exploiting supervised information is also demonstrated. PMID- 26352995 TI - Fast Edge Detection Using Structured Forests. AB - Edge detection is a critical component of many vision systems, including object detectors and image segmentation algorithms. Patches of edges exhibit well-known forms of local structure, such as straight lines or T-junctions. In this paper we take advantage of the structure present in local image patches to learn both an accurate and computationally efficient edge detector. We formulate the problem of predicting local edge masks in a structured learning framework applied to random decision forests. Our novel approach to learning decision trees robustly maps the structured labels to a discrete space on which standard information gain measures may be evaluated. The result is an approach that obtains realtime performance that is orders of magnitude faster than many competing state-of-the-art approaches, while also achieving state-of-the-art edge detection results on the BSDS500 Segmentation dataset and NYU Depth dataset. Finally, we show the potential of our approach as a general purpose edge detector by showing our learned edge models generalize well across datasets. PMID- 26352996 TI - Learning Discriminative Collections of Part Detectors for Object Recognition. AB - We propose a method to learn a diverse collection of discriminative parts from object bounding box annotations. Part detectors can be trained and applied individually, which simplifies learning and extension to new features or categories. We apply the parts to object category detection, pooling part detections within bottom-up proposed regions and using a boosted classifier with proposed sigmoid weak learners for scoring. On PASCAL VOC2010, we evaluate the part detectors' ability to discriminate and localize annotated keypoints and their effectiveness in detecting object categories. PMID- 26352997 TI - Multi-Region Active Contours with a Single Level Set Function. AB - Segmenting an image into an arbitrary number of coherent regions is at the core of image understanding. Many formulations of the segmentation problem have been suggested over the past years. These formulations include, among others, axiomatic functionals, which are hard to implement and analyze, and graph-based alternatives, which impose a non-geometric metric on the problem. We propose a novel method for segmenting an image into an arbitrary number of regions using an axiomatic variational approach. The proposed method allows to incorporate various generic region appearance models, while avoiding metrication errors. In the suggested framework, the segmentation is performed by level set evolution. Yet, contrarily to most existing methods, here, multiple regions are represented by a single non-negative level set function. The level set function evolution is efficiently executed through the Voronoi Implicit Interface Method for multi phase interface evolution. The proposed approach is shown to obtain accurate segmentation results for various natural 2D and 3D images, comparable to state-of the-art image segmentation algorithms. PMID- 26352998 TI - Normalized Compression Distance of Multisets with Applications. AB - Pairwise normalized compression distance (NCD) is a parameter-free, feature-free, alignment-free, similarity metric based on compression. We propose an NCD of multisets that is also metric. Previously, attempts to obtain such an NCD failed. For classification purposes it is superior to the pairwise NCD in accuracy and implementation complexity. We cover the entire trajectory from theoretical underpinning to feasible practice. It is applied to biological (stem cell, organelle transport) and OCR classification questions that were earlier treated with the pairwise NCD. With the new method we achieved significantly better results. The theoretic foundation is Kolmogorov complexity. PMID- 26352999 TI - Order Preserving Sparse Coding. AB - In this paper, we investigate order-preserving sparse coding for classifying structured data whose atomic features possess ordering relationships. Examples include time sequences where individual frame-wise features are temporally ordered, as well as still images (landscape, street view, etc.) where different regions of the image are spatially ordered. Classification of these structured data is often tackled by first decomposing the input data into individual atomic features, then performing sparse coding or other processing for each atomic feature vector independently, and finally aggregating individual responses to classify the input data. However, this heuristic approach ignores the underlying order of the individual atomic features within the input data, and results in suboptimal discriminative capability. In this work, we introduce an order preserving regularizer which aims to preserve the ordering structure of the reconstruction coefficients within the sparse coding framework. An efficient Nesterov-type smooth approximation method is developed for optimization of the new regularization criterion, with theoretically guaranteed error bound. We perform extensive experiments for time series classification on a synthetic dataset, several machine learning benchmarks, and an RGB-D human activity dataset. We also report experiments for scene classification on a benchmark image dataset. The encoded representation is discriminative and robust, and our classifier outperforms state-of-the-art methods on these tasks. PMID- 26353000 TI - Person Re-Identification by Iterative Re-Weighted Sparse Ranking. AB - In this paper we introduce a method for person re-identification based on discriminative, sparse basis expansions of targets in terms of a labeled gallery of known individuals. We propose an iterative extension to sparse discriminative classifiers capable of ranking many candidate targets. The approach makes use of soft- and hard- re-weighting to redistribute energy among the most relevant contributing elements and to ensure that the best candidates are ranked at each iteration. Our approach also leverages a novel visual descriptor which we show to be discriminative while remaining robust to pose and illumination variations. An extensive comparative evaluation is given demonstrating that our approach achieves state-of-the-art performance on single- and multi-shot person re identification scenarios on the VIPeR, i-LIDS, ETHZ, and CAVIAR4REID datasets. The combination of our descriptor and iterative sparse basis expansion improves state-of-the-art rank-1 performance by six percentage points on VIPeR and by 20 on CAVIAR4REID compared to other methods with a single gallery image per person. With multiple gallery and probe images per person our approach improves by 17 percentage points the state-of-the-art on i-LIDS and by 72 on CAVIAR4REID at rank 1. The approach is also quite efficient, capable of single-shot person re identification over galleries containing hundreds of individuals at about 30 re identifications per second. PMID- 26353001 TI - Pose Estimation and Segmentation of Multiple People in Stereoscopic Movies. AB - We describe a method to obtain a pixel-wise segmentation and pose estimation of multiple people in stereoscopic videos. This task involves challenges such as dealing with unconstrained stereoscopic video, non-stationary cameras, and complex indoor and outdoor dynamic scenes with multiple people. We cast the problem as a discrete labelling task involving multiple person labels, devise a suitable cost function, and optimize it efficiently. The contributions of our work are two-fold: First, we develop a segmentation model incorporating person detections and learnt articulated pose segmentation masks, as well as colour, motion, and stereo disparity cues. The model also explicitly represents depth ordering and occlusion. Second, we introduce a stereoscopic dataset with frames extracted from feature-length movies "StreetDance 3D" and "Pina". The dataset contains 587 annotated human poses, 1,158 bounding box annotations and 686 pixel wise segmentations of people. The dataset is composed of indoor and outdoor scenes depicting multiple people with frequent occlusions. We demonstrate results on our new challenging dataset, as well as on the H2view dataset from (Sheasby et al. ACCV 2012). PMID- 26353002 TI - Re-Identification in the Function Space of Feature Warps. AB - Person re-identification in a non-overlapping multicamera scenario is an open challenge in computer vision because of the large changes in appearances caused by variations in viewing angle, lighting, background clutter, and occlusion over multiple cameras. As a result of these variations, features describing the same person get transformed between cameras. To model the transformation of features, the feature space is nonlinearly warped to get the "warp functions". The warp functions between two instances of the same target form the set of feasible warp functions while those between instances of different targets form the set of infeasible warp functions. In this work, we build upon the observation that feature transformations between cameras lie in a nonlinear function space of all possible feature transformations. The space consisting of all the feasible and infeasible warp functions is the warp function space (WFS). We propose to learn a discriminating surface separating these two sets of warp functions in the WFS and to re-identify persons by classifying a test warp function as feasible or infeasible. Towards this objective, a Random Forest (RF) classifier is employed which effectively chooses the warp function components according to their importance in separating the feasible and the infeasible warp functions in the WFS. Extensive experiments on five datasets are carried out to show the superior performance of the proposed approach over state-of-the-art person re identification methods. We show that our approach outperforms all other methods when large illumination variations are considered. At the same time it has been shown that our method reaches the best average performance over multiple combinations of the datasets, thus, showing that our method is not designed only to address a specific challenge posed by a particular dataset. PMID- 26353003 TI - Shape, Illumination, and Reflectance from Shading. AB - A fundamental problem in computer vision is that of inferring the intrinsic, 3D structure of the world from flat, 2D images of that world. Traditional methods for recovering scene properties such as shape, reflectance, or illumination rely on multiple observations of the same scene to overconstrain the problem. Recovering these same properties from a single image seems almost impossible in comparison-there are an infinite number of shapes, paint, and lights that exactly reproduce a single image. However, certain explanations are more likely than others: surfaces tend to be smooth, paint tends to be uniform, and illumination tends to be natural. We therefore pose this problem as one of statistical inference, and define an optimization problem that searches for the most likely explanation of a single image. Our technique can be viewed as a superset of several classic computer vision problems (shape-from-shading, intrinsic images, color constancy, illumination estimation, etc) and outperforms all previous solutions to those constituent problems. PMID- 26353004 TI - Tree Topology Estimation. AB - Tree-like structures are fundamental in nature, and it is often useful to reconstruct the topology of a tree - what connects to what - from a two dimensional image of it. However, the projected branches often cross in the image: the tree projects to a planar graph, and the inverse problem of reconstructing the topology of the tree from that of the graph is ill-posed. We regularize this problem with a generative, parametric tree-growth model. Under this model, reconstruction is possible in linear time if one knows the direction of each edge in the graph - which edge endpoint is closer to the root of the tree - but becomes NP-hard if the directions are not known. For the latter case, we present a heuristic search algorithm to estimate the most likely topology of a rooted, three-dimensional tree from a single two-dimensional image. Experimental results on retinal vessel, plant root, and synthetic tree data sets show that our methodology is both accurate and efficient. PMID- 26353005 TI - Zero-Aliasing Correlation Filters for Object Recognition. AB - Correlation filters (CFs) are a class of classifiers that are attractive for object localization and tracking applications. Traditionally, CFs have been designed in the frequency domain using the discrete Fourier transform (DFT), where correlation is efficiently implemented. However, existing CF designs do not account for the fact that the multiplication of two DFTs in the frequency domain corresponds to a circular correlation in the time/spatial domain. Because this was previously unaccounted for, prior CF designs are not truly optimal, as their optimization criteria do not accurately quantify their optimization intention. In this paper, we introduce new zero-aliasing constraints that completely eliminate this aliasing problem by ensuring that the optimization criterion for a given CF corresponds to a linear correlation rather than a circular correlation. This means that previous CF designs can be significantly improved by this reformulation. We demonstrate the benefits of this new CF design approach with several important CFs. We present experimental results on diverse data sets and present solutions to the computational challenges associated with computing these CFs. Code for the CFs described in this paper and their respective zero-aliasing versions is available at http://vishnu.boddeti.net/projects/correlation filters.html. PMID- 26353006 TI - Meta-Parameter Free Unsupervised Sparse Feature Learning. AB - We propose a meta-parameter free, off-the-shelf, simple and fast unsupervised feature learning algorithm, which exploits a new way of optimizing for sparsity. Experiments on CIFAR-10, STL-10 and UCMerced show that the method achieves the state-of-the-art performance, providing discriminative features that generalize well. PMID- 26353007 TI - Sketch Matching on Topology Product Graph. AB - Sketch matching is the fundamental problem in sketch based interfaces. After years of study, it remains challenging when there exists large irregularity and variations in the hand drawn sketch shapes. While most existing works exploit topology relations and graph representations for this problem, they are usually limited by the coarse topology exploration and heuristic (thus suboptimal) similarity metrics between graphs. We present a new sketch matching method with two novel contributions. We introduce a comprehensive definition of topology relations, which results in a rich and informative graph representation of sketches. For graph matching, we propose topology product graph that retains the full correspondence for matching two graphs. Based on it, we derive an intuitive sketch similarity metric whose exact solution is easy to compute. In addition, the graph representation and new metric naturally support partial matching, an important practical problem that received less attention in the literature. Extensive experimental results on a real challenging dataset and the superior performance of our method show that it outperforms the state-of-the-art. PMID- 26353008 TI - 3D Palmprint Identification Using Block-Wise Features and Collaborative Representation. AB - Developing 3D palmprint recognition systems has recently begun to draw attention of researchers. Compared with its 2D counterpart, 3D palmprint has several unique merits. However, most of the existing 3D palmprint matching methods are designed for one-to-one verification and they are not efficient to cope with the one-to many identification case. In this paper, we fill this gap by proposing a collaborative representation (CR) based framework with l1-norm or l2-norm regularizations for 3D palmprint identification. The effects of different regularization terms have been evaluated in experiments. To use the CR-based classification framework, one key issue is how to extract feature vectors. To this end, we propose a block-wise statistics based feature extraction scheme. We divide a 3D palmprint ROI into uniform blocks and extract a histogram of surface types from each block; histograms from all blocks are then concatenated to form a feature vector. Such feature vectors are highly discriminative and are robust to mere misalignment. Experiments demonstrate that the proposed CR-based framework with an l2-norm regularization term can achieve much better recognition accuracy than the other methods. More importantly, its computational complexity is extremely low, making it quite suitable for the large-scale identification application. Source codes are available at http://sse.tongji.edu.cn/linzhang/cr3dpalm/cr3dpalm.htm. PMID- 26353009 TI - Effectiveness of Metyrapone in Treating Cushing's Syndrome: A Retrospective Multicenter Study in 195 Patients. AB - BACKGROUND: Cushing's syndrome (CS) is a severe condition with excess mortality and significant morbidity necessitating control of hypercortisolemia. There are few data documenting use of the steroidogenesis inhibitor metyrapone for this purpose. OBJECTIVE: The objective was to assess the effectiveness of metyrapone in controlling cortisol excess in a contemporary series of patients with CS. DESIGN: This was designed as a retrospective, multicenter study. SETTING: Thirteen University hospitals were studied. PATIENTS: We studied a total of 195 patients with proven CS: 115 Cushing's disease, 37 ectopic ACTH syndrome, 43 ACTH independent disease (adrenocortical carcinoma 10, adrenal adenoma 30, and ACTH independent adrenal hyperplasia 3). MEASUREMENTS: Measurements included biochemical parameters of activity of CS: mean serum cortisol "day-curve" (CDC) (target 150-300 nmol/L); 9 am serum cortisol; 24-hour urinary free cortisol (UFC). RESULTS: A total of 164/195 received metyrapone monotherapy. Mean age was 49.6 +/- 15.7 years; mean duration of therapy 8 months (median 3 mo, range 3 d to 11.6 y). There were significant improvements on metyrapone, first evaluation to last review: CDC (91 patients, 722.9 nmol/L [26.2 MUg/dL] vs 348.6 nmol/L [12.6 MUg/dL]; P < .0001); 9 am cortisol (123 patients, 882.9 nmol/L [32.0 MUg/dL] vs 491.1 nmol/L [17.8 MUg/dL]; P < .0001); and UFC (37 patients, 1483 nmol/24 h [537 MUg/24 h] vs 452.6 nmol/24 h [164 MUg/24 h]; P = .003). Overall, control at last review: 55%, 43%, 46%, and 76% of patients who had CDCs, UFCs, 9 am cortisol less than 331 nmol/L (12.0 MUg/dL), and 9 am cortisol less than upper limit of normal/600 nmol/L (21.7 MUg/dL). Median final dose: Cushing's disease 1375 mg; ectopic ACTH syndrome 1500 mg; benign adrenal disease 750 mg; and adrenocortical carcinoma 1250 mg. Adverse events occurred in 25% of patients, mostly mild gastrointestinal upset and dizziness, usually within 2 weeks of initiation or dose increase, all reversible. CONCLUSIONS: Metyrapone is effective therapy for short- and long-term control of hypercortisolemia in CS. PMID- 26353010 TI - Afirma Benign Thyroid Nodules Show Similar Growth to Cytologically Benign Nodules During Follow-Up. AB - CONTEXT: The Afirma gene expression classifier (GEC) is a molecular diagnostic test that has a high negative predictive value for ruling out malignancy in thyroid nodules with indeterminate cytology. Many patients with a cytologically indeterminate and GEC benign (Cyto-I/GEC-B) nodule undergo monitoring instead of diagnostic surgery, but few data describe their follow-up. OBJECTIVE: The objective of the study was to determine the sonographic changes and clinical outcomes for patients with Cyto-I/GEC-B nodules compared with patients with cytologically benign (Cyto-B) nodules. DESIGN: This was a retrospective analysis of consecutive Cyto-I/GEC-B nodules evaluated at Brigham and Women's Hospital compared with Cyto-B nodules. MAIN OUTCOMES: Nodule growth of 20% or greater in two dimensions or of 50% or greater in volume, change in sonographic features, and rates of repeat fine-needle aspiration, thyroidectomy, and malignancy. RESULTS: Ninety-five Cyto-I/GEC-B nodules in 90 patients were identified. Five patients underwent primary surgical resection. Of the remaining 90 nodules, 58 (64.4%) had sonographic follow-up available at a median of 13 months (range 4-40 mo). Cyto-I/GEC-B nodules showed similar growth compared with 1224 Cyto-B nodules using either of the following criteria: 20% or greater in two dimensions (8.6% vs 8.3%, P = .80) or 50% or greater in volume (17.2% vs 13.8%, P = .44). Thyroidectomies were more frequent in the Cyto-I/GEC-B group (13.8% vs 0.9%, P < .0001), but cancer was found in only one patient, with no evidence of persistent disease after initial treatment. CONCLUSIONS: Cyto-I/GEC-B nodules demonstrate similar growth to Cyto-B nodules during follow-up. Although Cyto-I/GEC-B nodules were more frequently resected, only one malignancy was found. These data suggest that reassessment of Cyto-I/GEC-B nodules may be performed similarly to those with benign cytology. PMID- 26353011 TI - Temporal-Spatial Pattern of Carbon Stocks in Forest Ecosystems in Shaanxi, Northwest China. AB - The precise and accurate quantitative evaluation of the temporal and spatial pattern of carbon (C) storage in forest ecosystems is critical for understanding the role of forests in the global terrestrial C cycle and is essential for formulating forest management policies to combat climate change. In this study, we examined the C dynamics of forest ecosystems in Shaanxi, northwest China, based on four forest inventories (1989-1993, 1994-1998, 1999-2003, and 2004-2008) and field-sampling measurements (2012). The results indicate that the total C storage of forest ecosystems in Shaanxi increased by approximately 29.3%, from 611.72 Tg in 1993 to 790.75 Tg in 2008, partially as a result of ecological restoration projects. The spatial pattern of C storage in forest ecosystems mainly exhibited a latitude-zonal distribution across the province, increasing from north (high latitude) to south (low latitude) generally, which signifies the effect of environmental conditions, chiefly water and heat related factors, on forest growth and C sequestration. In addition, different data sources and estimation methods had a significant effect on the results obtained, with the C stocks in 2008 being considerably overestimated (864.55 Tg) and slightly underestimated (778.07 Tg) when measured using the mean C density method and integrated method, respectively. Overall, our results demonstrated that the forest ecosystem in Shaanxi acted as a C sink over the last few decades. However, further studies should be carried out with a focus on adaption of plants to environmental factors along with forest management for vegetation restoration to maximize the C sequestration potential and to better cope with climate change. PMID- 26353013 TI - SILAC-Based Mass Spectrometry Analysis Reveals That Epibrassinolide Induces Apoptosis via Activating Endoplasmic Reticulum Stress in Prostate Cancer Cells. AB - Epibrassinolide (EBR) is a polyhydroxylated sterol derivative and biologically active compound of the brassinosteroids. In addition to well-described roles in plant growth, EBR induces apoptosis in the LNCaP prostate cancer cells expressing functional androgen receptor (AR). Therefore, it is suggested that EBR might have an inhibitory potential on androgen receptor signaling pathway. However, the mechanism by which EBR exerts its effects on LNCaP is poorly understood. To address this gap in knowledge, we used an unbiased global proteomics approach, i.e., stable-isotope labeling by amino acids in cell culture (SILAC). In total, 964 unique proteins were identified, 160 of which were differentially expressed after 12 h of EBR treatment. The quantification of the differentially expressed proteins revealed that the expression of the unfolded protein response (UPR) chaperone protein, calreticulin (CALR), was dramatically downregulated. The decrease in CALR expression was also validated by immunoblotting. Because our data revealed the involvement of the UPR in response to EBR exposure, we evaluated the expression of the other UPR proteins. We demonstrated that EBR treatment downregulated calnexin and upregulated BiP and IRE1alpha expression levels and induced CHOP translocation from the cytoplasm to nucleus. The translocation of CHOP was associated with caspase-9 and caspase-3 activation after a 12 h EBR treatment. Co-treatment of EBR with rapamycin, an upstream mTOR pathway inhibitor, prevented EBR-induced cell viability loss and PARP cleavage in LNCaP prostate cancer cells, suggesting that EBR could induce ER stress in these cells. In addition, we observed similar results in DU145 cells with nonfunctional androgen receptor. When proteasomal degradation of proteins was blocked by MG132 co-treatment, EBR treatment further induced PARP cleavage relative to drug treatment alone. EBR also induced Ca2+ sequestration, which confirmed the alteration of the ER pathway due to drug treatment. Therefore, we suggest that EBR promotes ER stress and induces apoptosis. PMID- 26353012 TI - Evaluating the Photoprotective Effects of Ochre on Human Skin by In Vivo SPF Assessment: Implications for Human Evolution, Adaptation and Dispersal. AB - Archaeological indicators of cognitively modern behaviour become increasingly prevalent during the African Middle Stone Age (MSA). Although the exploitation of ochre is viewed as a key feature of the emergence of modern human behaviour, the uses to which ochre and ochre-based mixtures were put remain ambiguous. Here we present the results of an experimental study exploring the efficacy of ochre as a topical photoprotective compound. This is achieved through the in vivo calculation of the sun protection factor (SPF) values of ochre samples obtained from Ovahimba women (Kunene Region, Northern Namibia) and the Palaeozoic Bokkeveld Group deposits of the Cape Supergroup (Western Cape Province, South Africa). We employ visible spectroscopy, energy-dispersive X-ray fluorescence (ED XRF), X-ray diffraction (XRD) and granulometric analyses to characterise ochre samples. The capacity of ochre to inhibit the susceptibility of humans to the harmful effects of exposure to ultraviolet radiation (UVR) is confirmed and the mechanisms implicated in the efficacy of ochre as a sunscreen identified. It is posited that the habitual application of ochre may have represented a crucial innovation for MSA humans by limiting the adverse effects of ultraviolet exposure. This may have facilitated the colonisation of geographic regions largely unfavourable to the constitutive skin colour of newly arriving populations. PMID- 26353014 TI - Multinucleate cell angiohistiocytoma-like features around a ganglion. PMID- 26353015 TI - Children with recurrent psychosomatic abdominal pain display increased morning salivary cortisol and high serum cortisol concentrations. PMID- 26353016 TI - Depth-Related Effects on a Meiofaunal Community Dwelling in the Periphyton of a Mesotrophic Lake. AB - Periphyton is a complex assemblage of micro- and meiofauna embedded in the organic matrix that coats most submerged substrate in the littoral of lakes. The aim of this study was to better understand the consequences of depth-level fluctuation on a periphytic community. The effects of light and wave disturbance on the development of littoral periphyton were evaluated in Lake Erken (Sweden) using an experimental design that combined in situ shading with periphyton depth transfers. Free-living nematodes were a major contributor to the meiofaunal community. Their species composition was therefore used as a proxy to distinguish the contributions of light- and wave-related effects. The periphyton layer was much thicker at a depth of 30 cm than at 200 cm, as indicated by differences in the amounts of organic and phototrophic biomass and meiofaunal and nematode densities. A reduction of the depth-level of periphyton via a transfer from a deep to a shallow location induced rapid positive responses by its algal, meiofaunal, and nematode communities. The slower and weaker negative responses to the reverse transfer were attributed to the potentially higher resilience of periphytic communities to increases in the water level. In the shallow littoral of the lake, shading magnified the effects of phototrophic biomass erosion by waves, as the increased exposure to wave shear stress was not compensated for by an increase in photosynthesis. This finding suggests that benthic primary production will be strongly impeded in the shallow littoral zones of lakes artificially shaded by construction or embankments. However, regardless of the light constraints, an increased exposure to wave action had a generally positive short-term effect on meiofaunal density, by favoring the predominance of species able to anchor themselves to the substrate, especially the Chromadorid nematode Punctodora ratzeburgensis. PMID- 26353017 TI - Ongoing Discussions on Reliability of Diagnosis of Transient Ischemic Attack. PMID- 26353018 TI - From the Editor. PMID- 26353019 TI - Creating the Conditions That Promote Community Health Worker Success. PMID- 26353020 TI - Discovering Potential: A Glimpse of My Journey as a Community Health Worker. PMID- 26353021 TI - Thirty-four Years Working Hand in Hand With Community Health Workers: A Doctor's Perspective. AB - The author, a physician, describes her long history of working with community health workers (CHWs), as well as her admiration for her colleagues in CHW programs and for the late Dr Eva Salber. CHWs have a unique capability not only to serve their communities but also to transform American health care and public health. It is in society's interest to utilize many more CHWs in diverse roles and settings. This requires thoughtful program design, recruitment, trust, support, and full integration of CHWs into professional teams. PMID- 26353022 TI - The Role of Evaluation in Developing and Sustaining Community Health Worker Coalitions: The Example of the Michigan Community Health Worker Alliance. AB - Community health workers (CHWs) have demonstrated effectiveness in improving health outcomes and addressing health inequities. Statewide CHW coalitions are supporting expansion of the CHW workforce and influencing health policy. Evaluations can play a key role in sustaining coalitions. This article discusses how evaluation has informed the development, processes, and initiatives of the Michigan Community Health Worker Alliance. We highlight the Michigan Community Health Worker Alliance's internal process evaluation, a statewide survey of CHW programs, and other evaluation activities to illustrate how CHW coalitions can use participatory evaluation to develop and reinforce coalition strengths and accomplish mutual goals. PMID- 26353023 TI - "It's In My Veins": Exploring the Role of an Afrocentric, Popular Education-Based Training Program in the Empowerment of African American and African Community Health Workers in Oregon. AB - The role racism and other social determinants of health play in the creation of health inequities in African American communities in the United States is increasingly understood. In this article, we explore the effectiveness of an Afrocentric, popular education-based community health worker (CHW) training program in creating positive change among CHW participants and their communities in Portland, Oregon. Findings suggest that CHW participants experienced 4 types of awakening, in addition to changes in their interaction with their family members and increased community involvement. The CHWs identified group bond, Afrocentrism, public health knowledge, popular education, facilitators, and time management as important elements of an effective training program for this community. Psychological empowerment, self-reported health status, and health behavior among participants generally increased over time, but changes were not statistically significant. PMID- 26353024 TI - Promotores As Advocates for Community Improvement: Experiences of the Western States REACH Su Comunidad Consortium. AB - The REACH Su Comunidad Consortium worked with 10 communities to address disparities in access to healthy food and physical activity opportunities among Hispanic populations through policy, systems, and environmental (PSE) strategies. Community health workers took leadership roles in the implementation of PSE strategies in partnership with local multisector coalitions. This article describes the role of community health workers in PSE change, the technical and professional development support provided to the REACH Su Comunidad Communities, and highlights professional development needs of community health workers engaging in PSE strategies. PMID- 26353025 TI - Diabetes Connect: Developing a Mobile Health Intervention to Link Diabetes Community Health Workers With Primary Care. AB - Community health worker (CHW) interventions can help improve diabetes self management and health outcomes. There is limited evidence on how to effectively integrate CHW programs with primary care efforts. Mobile health technology (mHealth) can connect CHWs to members of the health care team and enhance care. We tested a model for the integration of a CHW-delivered mHealth intervention to improve diabetes self-management. Seventy-two African American patients with diabetes were followed using the mHealth tool. This project partnered an academic institution, a safety-net clinic, and African American churches. The integration of mHealth technology into CHW programs was successfully achieved and readily accepted. PMID- 26353026 TI - TROT Line: Live and Direct From the Republic of Texas. PMID- 26353027 TI - Intimate partner violence and engagement in HIV care and treatment among women: a systematic review and meta-analysis. AB - OBJECTIVE: We aimed to estimate the odds of engagement in HIV care and treatment among HIV-positive women reporting intimate partner violence (IPV). DESIGN: We systematically reviewed the literature on the association between IPV and engagement in care. Data sources included searches of electronic databases (PubMed, Web of Science, CINAHL and PsychoInfo), hand searches and citation tracking. METHODS: Two reviewers screened 757 full-text articles, extracted data and independently appraised study quality. Included studies were peer-reviewed and assessed IPV alongside engagement in care outcomes: antiretroviral treatment (ART) use; self-reported ART adherence; viral suppression; retention in HIV care. Odds ratios (ORs) were pooled using random effects meta-analysis. RESULTS: Thirteen cross-sectional studies among HIV-positive women were included. Measurement of IPV varied, with most studies defining a 'case' as any history of physical and/or sexual IPV. Meta-analysis of five studies showed IPV to be significantly associated with lower ART use [OR 0.79, 95% confidence interval (95% CI) 0.64-0.97]. IPV was associated with poorer self-reported ART adherence in six studies (OR 0.48, 95% CI 0.30-0.75) and lower odds of viral load suppression in seven studies (OR 0.64, 95% CI 0.46-0.90). Lack of longitudinal data and measurement considerations should temper interpretation of these results. CONCLUSION: IPV is associated with lower ART use, half the odds of self reported ART adherence and significantly worsened viral suppression among women. To ensure the health of HIV-positive women, it is essential for clinical programmes to address conditions that impact engagement in care and treatment. IPV is one such condition, and its association with declines in ART use and adherence requires urgent attention. PMID- 26353028 TI - Dimensional reduction of duplex DNA under confinement to nanofluidic slits. AB - There has been much interest in the dimensional properties of double-stranded DNA (dsDNA) confined to nanoscale environments as a problem of fundamental importance in both biological and technological fields. This has led to a series of measurements by fluorescence microscopy of single dsDNA molecules under confinement to nanofluidic slits. Despite the efforts expended on such experiments and the corresponding theory and simulations of confined polymers, a consistent description of changes of the radius of gyration of dsDNA under strong confinement has not yet emerged. Here, we perform molecular dynamics (MD) simulations to identify relevant factors that might account for this inconsistency. Our simulations indicate a significant amplification of excluded volume interactions under confinement at the nanoscale due to the reduction of the effective dimensionality of the system. Thus, any factor influencing the excluded volume interaction of dsDNA, such as ionic strength, solution chemistry, and even fluorescent labels, can greatly influence the dsDNA size under strong confinement. These factors, which are normally less important in bulk solutions of dsDNA at moderate ionic strengths because of the relative weakness of the excluded volume interaction, must therefore be under tight control to achieve reproducible measurements of dsDNA under conditions of dimensional reduction. By simulating semi-flexible polymers over a range of parameter values relevant to the experimental systems and exploiting past theoretical treatments of the dimensional variation of swelling exponents and prefactors, we have developed a novel predictive relationship for the in-plane radius of gyration of long semi flexible polymers under slit-like confinement. Importantly, these analytic expressions allow us to estimate the properties of dsDNA for the experimentally and biologically relevant range of contour lengths that is not currently accessible by state-of-the-art MD simulations. PMID- 26353029 TI - Pediatric Vaccine Adjuvants: Components of the Modern Vaccinologist's Toolbox. PMID- 26353030 TI - Risk Factors for Craniotomy or Spinal Fusion Surgical Site Infection. AB - BACKGROUND: Surgical site infections (SSIs) occur in approximately 700 pediatric patients annually and are associated with increased morbidity, mortality and cost. The aim of this study is to determine risk factors for SSI among pediatric patients undergoing craniotomy and spinal fusion. METHODS: This is a retrospective case-control study. Cases were craniotomy or spinal fusion patients with SSI as defined by Centers for Disease Control and Prevention criteria with surgery performed from January 1, 2008 to July 31, 2009. For each case patient, 3 uninfected controls were randomly selected among patients who underwent the same procedure as the case patient within 1 month. We performed analyses of risk factors for craniotomy and spinal fusion SSI separately and as a combined outcome variable. RESULTS: Underweight body mass index, increased time at lowest body temperature, increased interval to antibiotic redosing, the combination of vancomycin and cefazolin for prophylaxis, longer preoperative and postoperative intensive care unit stay and anticoagulant use at 2 weeks postoperatively were associated with an increased risk of SSI in the combined analysis of craniotomy and spinal fusion. Forty-seven percent of cases and 27% of controls received preoperative antibiotic doses that were inappropriately low because of their weight. CONCLUSIONS: We identified modifiable risk factors for SSI including antibiotic dosing and body temperature during surgery. Preoperative antibiotic administration is likely to benefit from standard processes. Further studies of risk benefit for prolonged low body temperature during procedures are needed to determine the optimal balance between neuroprotection and potential immunosuppression associated with low body temperature. PMID- 26353031 TI - Patterns of Fever in Children After Primary Treatment for Kawasaki Disease. AB - BACKGROUND: We sought to determine if fever in the early postintravenous immunoglobulin (IVIG) time period (first 36 hours after IVIG completion) for Kawasaki disease, with or without additional infliximab, can predict IVIG resistance and coronary artery abnormalities (CAA). METHODS: Acute Kawasaki disease subjects enrolled in a clinical trial of infliximab plus IVIG (n = 96) versus placebo/IVIG (n = 94) had temperatures recorded every 6 hours after completion of IVIG infusion. Fever was defined as temperature >38.0 degrees C; patients with persistent or recrudescent fever >36 hours after completion of IVIG were classified as IVIG resistant. Multivariable logistic regression by fever pattern was performed to predict outcomes (IVIG resistance and CAA). RESULTS: There was no difference in the time to defervescence between the infliximab/IVIG group (n = 96) versus placebo/IVIG group (n = 94). There was no fever after completion of IVIG in the majority of subjects [66% of those with no CAA (n = 139) and 76.5% of those with CAA, (n = 51)]. Although subjects with at least 1 fever 24-36 hours post-IVIG had a higher probability of IVIG resistance [odds ratio = 30.6 (95% confidence interval: 6.7-139.8); P < 0.0001], fever at 24-36 hours was not associated with higher likelihood of CAA. There were also 11% (n = 19) of IVIG responders who had fever at 24-36 hours post-IVIG. The majority of subjects with CAA (43 of 51, 84.3%) were identified by the initial echocardiogram, so the effect of fever on development of CAA could not be assessed. CONCLUSIONS: Fever in the first 36 hours after IVIG completion is not predictive of CAA. Our data support refraining from retreatment until 36 hours after completion of IVIG. PMID- 26353032 TI - Superinfection and the coevolution of parasite virulence and host recovery. AB - Parasite strategies of host exploitation may be affected by host defence strategies and multiple infections. In particular, within-host competition between multiple parasite strains has been shown to select for higher virulence. However, little is known on how multiple infections could affect the coevolution between host recovery and parasite virulence. Here, we extend a coevolutionary model introduced by van Baalen (Proc. R. Soc. B, 265, 1998, 317) to account for superinfection. When the susceptibility to superinfection is low, we recover van Baalen's results and show that there are two potential evolutionary endpoints: one with avirulent parasites and poorly defended hosts, and another one with high virulence and high recovery. However, when the susceptibility to superinfection is above a threshold, the only possible evolutionary outcome is one with high virulence and high investment into defence. We also show that within-host competition may select for lower host recovery, as a consequence of selection for more virulent strains. We discuss how different parasite and host strategies (superinfection facilitation, competitive exclusion) as well as demographic and environmental parameters, such as host fecundity or various costs of defence, may affect the interplay between multiple infections and host-parasite coevolution. Our model shows the interplay between coevolutionary dynamics and multiple infections may be affected by crucial mechanistic or ecological details. PMID- 26353033 TI - Modulation of the aggregation properties of sodium deoxycholate in presence of hydrophilic imidazolium based ionic liquid: water dynamics study to probe the structural alteration of the aggregates. AB - In this article, we have investigated the effect of a hydrophilic ionic liquid, 1 butyl-3-methylimidazolium tetrafluoroborate ([bmim]-BF4), on the aggregation properties of a biological surfactant, sodium deoxycholate (NaDC), in water. In solution, unlike conventional surfactants it shows stepwise aggregation and the effect of the conventional ionic liquid on the aggregation properties is rather interesting. We have observed concentration dependent dual role of the ionic liquid; at their low concentration, the aggregated structure of NaDC reorganizes itself into an elongated rod like structure. However, the aggregated network is disintegrated into small aggregates upon further addition of ionic liquid. TEM (Transmission Electron Microscopy), SEM (Scanning Electron Microscopy) and FLIM (Fluorescence Lifetime Imaging Microscopy) images also confirmed the structural alteration of NaDC upon varying the concentration of the ionic liquid. The proton NMR data indicate that hydrophobic as well as electrostatic interaction is solely responsible for such structural adaptation of NaDC in the presence of an ionic liquid. The host-guest interaction inside the aggregates is monitored using Coumarin-153 (C-153) and the location of C-153 is probed by varying the excitation wavelength from 375 nm to 440 nm and the two binding sites of the aggregates are affected in a different fashion in the presence of ionic liquid. Excitation in the blue region selects the fluorophores which preferably bind to the buried region of the aggregates, whereas 440 nm excitation corresponds to the guest molecules which are exposed to the solvent molecules. The average solvation time of C-153 is increased in the presence of 1.68 wt% [bmim]-BF4 at lambdaexc = 440 nm i.e. the probe molecules relocate themselves to a more restricted region. However, the average solvation time became 2.6 times faster in the presence of 11.2 wt% [bmim]-BF4, which corresponds to a more polar and exposed region. The time resolved anisotropy measurements and polarity determined by pyrene also supported our results in addition to solvation dynamics measurements. In summary, ionic liquids can modulate the host-guest interaction of bile salt aggregates, which can be used as nanocarriers for drug delivery. PMID- 26353034 TI - Letter From the Editor: Reflections on Lugano. PMID- 26353035 TI - Second-generation ALK inhibitors. PMID- 26353036 TI - The potential threat to blood transfusion safety of emerging infectious disease agents. PMID- 26353037 TI - Highlights in breast cancer from the 2015 American Society of Clinical Oncology annual meeting. PMID- 26353038 TI - Stool DNA testing: a new, noninvasive option for colorectal cancer screening. PMID- 26353039 TI - Managing primary central nervous system lymphoma. PMID- 26353040 TI - The effect of cancer treatment on cognitive function. AB - Cognitive dysfunction is an increasingly recognized complication of cancer and its treatment. Most research in this arena has found that a subset of patients appear to be vulnerable to this complication even after treatment has ended, and often have difficulties with multitasking, short-term memory, word-finding, attention, or concentration. The mechanisms underlying these cognitive changes are not fully elucidated but may include direct neurotoxic effects of therapy, oxidative damage, and genetic predisposition. Compelling evidence has accumulated for the role of immune dysregulation and neurotoxicity from inflammatory cytokines. A gold standard for subjective or objective assessment of cancer treatment-related cognitive changes has yet to be established. Current options to assess cognitive function include neuropsychological testing, functional neuroimaging, and subjective assessments. Pharmacologic treatment options for this clinical problem are modest and limited. Nonpharmacologic treatments, including cognitive rehabilitation programs, are an emerging area of research for the management of cancer treatment-related cognitive changes. PMID- 26353041 TI - Immunotherapy or molecularly targeted therapy: what is the best initial treatment for stage IV BRAF-mutant melanoma? AB - The recent developments in BRAF-targeted therapy and checkpoint inhibitor immunotherapies for metastatic melanoma patients have led to better tolerability and markedly improved clinical outcomes, including higher objective response rates and longer survival. Treatment planning has become complex in patients with metastatic BRAF-mutant melanoma, with several options for BRAF- and/or MEK targeted therapy (vemurafenib, dabrafenib, and trametinib) and immunotherapy (interleukin 2, ipilimumab, pembrolizumab, and nivolumab). Clinicians must weigh various patient factors, including the extent of disease (eg, symptomatic visceral metastases vs limited disease) and central nervous system involvement, as well as factors related to the therapeutic agent, such as rate of clinical response, durability of response, and impact on median and long-term survival. The combination regimen of dabrafenib plus trametinib has become a standard treatment strategy, and ipilimumab plus nivolumab is emerging as a promising treatment strategy. In this review, we discuss the benchmark trials leading to the approval of these new agents and provide emerging data on their use in sequence and impact on overall survival, with the goal of helping oncologists navigate treatment decisions for patients with metastatic BRAF-mutant melanoma. PMID- 26353042 TI - Current and novel treatment options for peripheral T-cell lymphoma. PMID- 26353043 TI - Influenza vaccine for 2015-2016. PMID- 26353044 TI - Choice of contraceptives. PMID- 26353045 TI - Simultaneous Interaction of Hydrophilic and Hydrophobic Solvents with Ethylamino Neurotransmitter Radical Cations: Infrared Spectra of Tryptamine(+)-(H2O)m-(N2)n Clusters (m,n <= 3). AB - Solvation of biomolecules by a hydrophilic and hydrophobic environment strongly affects their structure and function. Here, the structural, vibrational, and energetic properties of size-selected clusters of the microhydrated tryptamine cation with N2 ligands, TRA(+)-(H2O)m-(N2)n (m,n <= 3), are characterized by infrared photodissociation spectroscopy in the 2800-3800 cm(-1) range and dispersion-corrected density functional theory calculations at the omegaB97X-D/cc pVTZ level to investigate the simultaneous solvation of this prototypical neurotransmitter by dipolar water and quadrupolar N2 ligands. In the global minimum structure of TRA(+)-H2O generated by electron ionization, H2O is strongly hydrogen-bonded (H-bonded) as proton acceptor to the acidic indolic NH group. In the TRA(+)-H2O-(N2)n clusters, the weakly bonded N2 ligands do not affect the H bonding motif of TRA(+)-H2O and are preferentially H-bonded to the OH groups of the H2O ligand, whereas stacking to the aromatic pi electron system of the pyrrole ring of TRA(+) is less favorable. The natural bond orbital analysis reveals that the H-bond between the N2 ligand and the OH group of H2O cooperatively strengthens the adjacent H-bond between the indolic NH group of TRA(+) and H2O, while pi stacking is slightly noncooperative. In the larger TRA(+)-(H2O)m clusters, the H2O ligands form a H-bonded solvent network attached to the indolic NH proton, again stabilized by strong cooperative effects arising from the nearby positive charge. Comparison with the corresponding neutral TRA (H2O)m clusters illustrates the strong impact of the excess positive charge on the structure of the microhydration network. PMID- 26353046 TI - Chemical Typification of the Sugarcane Spirits Produced in Sao Paulo State. AB - To typify Sao Paulo State sugarcane spirits, 37 chemical compounds were analyzed in 81 Brazilian sugarcane spirits (cachaca), which were produced in different cities from Sao Paulo State. Among these samples, 56 were distilled in copper alembics, and the other 25 were distilled in steel columns. Hierarchical cluster analysis and principal component analysis were performed with both chemical data sets. The chemical profiles of the cachacas distilled in the column apparatus formed 4 specific clusters, which correspond to 4 distinct geographic regions of Sao Paulo State. For the cachacas that were distilled in copper alembics, 2 cachaca clusters were formed; however, no correlation between their respective chemical similarities and geographical origins was observed. PRACTICAL APPLICATION: This study aims to differentiate the many sugarcane spirits that are produced throughout Brazil's Sao Paulo State using chemical analysis with chemometric tools. This contribution is expected to improve the production process of cachacas, map the regions that produce the best cachacas, and assure consumers about a product's provenance. PMID- 26353047 TI - A study of starch gelatinisation behaviour in hydrothermally-processed plant food tissues and implications for in vitro digestibility. AB - The aim of this study was to investigate the role of the plant food matrix in influencing the extent of starch gelatinisation during hydrothermal processing, and its implications for starch digestibility. Differential scanning calorimetry (DSC) was used to provide a detailed examination of the gelatinisation behaviour of five distinct size fractions (diameters <0.21 to 2.58 mm) of milled chickpea and durum wheat. Gelatinisation parameters were obtained from the DSC thermograms and concomitant microscopy analyses were performed. The estimated terminal extent of gelatinisation (TEG) was compared with our previously published data for in vitro starch digestibility of the same food materials. We observed clear differences in the gelatinisation behaviour of matched size-fractions of chickpeas and durum wheat. In chickpea materials, the TEG values (34-100%) were inversely related to particle size, whereas in durum wheat, no size-dependent limitations on TEG were observed. The TEG values were completely consistent with the extent of starch amylolysis in all size fractions of both durum wheat and chickpea. Microstructural analysis following hydrothermal processing confirmed the presence of some partially gelatinised birefringent starch within intact chickpea cells. Birefringent starch granules were not present in any of the processed fractions of durum wheat. The differences in gelatinisation behaviour of these plant species seem to reflect the individual cell wall properties of these materials. These findings demonstrate the applicability of DSC to real food materials to provide insight into the mechanisms by which the food matrix (particularly the plant cell walls) influences gelatinisation, and consequently, starch amylolysis. PMID- 26353048 TI - Induction of apoptosis by an ethanol extract of Poria cocos Wolf. in human leukemia U937 cells. AB - Poria cocos Wolf., which belongs to the Polyporaceae family, has been widely used as an Oriental traditional herbal medicine for centuries. Its sclerotium has been reported to possess a wide spectrum of pharmacological activities, including free radical scavenging, anti-viral, anti-microbial, anti-inflammatory and anticancer activities. However, the cellular and molecular mechanisms of apoptosis induction by P. cocos in human cancer cells are poorly understood. In the present study, we investigated the pro-apoptotic potential of an ethanol extract of P. cocos sclerotium (EEPC) in human leukemia U937 cells in vitro. We found that EEPC induced anti-proliferative effects in U937 cells in a concentration- and time dependent manner, which was due to apoptotic induction, as evident from morphological changes and flow cytometric assays. EEPC-induced apoptosis of U937 cells was associated with an increase in the Bax:Bcl-2 ratio, the release of cytochrome c to the cytosol, and a decrease in the expression of an inhibitor of the apoptosis family of proteins. The events were accompanied by activation of caspase-8, -9 and -3, and cleaved poly(ADP-ribose) polymerase, suggesting the involvement of both the intrinsic and extrinsic apoptotic cascades. In addition, the overexpression of Bcl-2 caused a significant attenuation of EEPC-induced caspase activation, degradation of PARP, and the collapse of mitochondrial membrane potential, and thereby reversed EEPC-induced cell apoptosis and growth inhibition. Collectively, these data provide insights into the molecular mechanisms underlying EEPC-induced apoptosis in U937 cells, suggesting that EEPC may be a new therapeutic option for the treatment of leukemia. PMID- 26353049 TI - Generation and characterization of mice with a conditional null allele of the HtrA4 gene. AB - High temperature requirement factor A4 (HtrA4) is a member of the HtrA family of serine peptidases involved in regulating protein-protein interactions. Little is known regarding the function of HtrA4 in humans and in mouse models. To gain insights into the role of HtrA4 in vivo, mice were generated with a conditional null allele of HtrA4 by flanking exons 4, 5 and 6 with loxP sites. Cre-mediated recombination, using a ubiquitously active Rosa26-Cre line, resulted in the deletion of the floxed region in the mouse genome. Mice homozygous for the recombinant allele (HtrA4-/-) were viable, fertile and appeared to be normal. The HtrA4 protein was detectable in coronary vessels and in the placenta. However, the loss of HtrA4 affected neither the basic heart nor placental functions. These mice, featuring a conditional null allele of HtrA4, may provide a valuable tool to investigate the role of HtrA4 in development and pathogenesis of coronary heart disease and preeclampsia. PMID- 26353050 TI - Epidemiology of serotype Asia 1 foot-and-mouth disease virus in China. AB - This manuscript provides insight into the epidemiology of serotype Asia 1 foot and-mouth disease virus in China. The spatial distribution and temporal dynamics of this serotype, which China reported for the first time after 47 years in 2005, suggests that it may have become endemic in the region. PMID- 26353051 TI - Molecular characterisation of foot-and-mouth disease viruses from Pakistan, 2005 2008. AB - Foot-and-mouth disease (FMD), an economically important disease of cloven-hoofed animals, is endemic in Pakistan where three virus serotypes are present (O, A and Asia 1). Fifty-eight clinical samples collected between 2005 and 2008 from animals with suspected FMD in various locations in Pakistan were subjected to virus isolation on primary cell culture, antigen ELISA and real-time RT-PCR (rRT PCR). Viruses were isolated from 32 of these samples and identified as FMDV type O (n = 31) or type A (n = 1). Foot-and-mouth disease virus (FMDV) genome was detected in a further 11 samples by real-time RT-PCR. Phylogenetic analyses of the VP1 nucleotide sequences showed that all of the type O viruses belonged to the MIDDLE EAST-SOUTH ASIA topotype with the majority belonging to the PanAsia-2 lineage; a single example of the older PanAsia lineage was identified. The single FMDV type A virus belonged to the ASIA topotype, but did not cluster with known strains that are currently circulating (such as Iran-05) and was not closely related to other type A viruses from the region. These findings demonstrate the widespread distribution of O-PanAsia-2 in Pakistan and the presence of undisclosed novel type A lineages in the region. PMID- 26353052 TI - Experimental infection of giraffe (Giraffa camelopardalis) with SAT-1 and SAT-2 foot-and-mouth disease virus. AB - The potential role of giraffe (Giraffa camelopardalis) in the epidemiology and spread of foot-and-mouth disease (FMD) SAT types was investigated by experimental infection and detection of virus in excretions using virus isolation on primary pig kidney cell cultures. In two experiments separated by a period of 24 months, groups of four animals were needle infected with a SAT-1 or SAT-2 virus, respectively and two in-contact controls were kept with each group. Viraemia was detected 3-9 days post-infection and virus isolated from mouth washes and faeces only occasionally up to day 13. The SAT-1 virus was transmitted to only one in contact control animal, probably via saliva that contained virus from vesicles in the mouth of a needle-infected animal. None of the animals infected with the SAT 2 virus had any vesicles in the mouth, and there was no evidence of transmission to the in-contact controls. No virus was detected in probang samples for the duration of the experiments (60 days post-infection), indicating that persistent infection probably did not establish with either of these isolates. Giraffe most likely do not play an important role in FMD dissemination. Transmission of infection would possibly occur only during close contact with other animals when mouth vesicles are evident. PMID- 26353053 TI - The detection and genetic characterization based on the S1 gene region of BCoVs from respiratory and enteric infections in Turkey. AB - We investigated bovine coronavirus (BCoV) as an etiological agent in cattle with clinical respiratory and digestive signs using 147 feces and 199 nasal swab samples. A total of 18 test samples (16 feces and 2 nasal swap samples) were detected positive by ELISA and/or RT-PCR targeting the BCoV N gene. The partial S1 gene regions of BCoVs (An-4 and An-11) detected in feces samples from two herd mate dairy calves were compared. Virological and serological results indicated that BCoVs are widespread in Turkey and are likely etiological agents in diarrhea cases in calves. PMID- 26353055 TI - A Minimax Framework for Classification with Applications to Images and High Dimensional Data. AB - This paper introduces a minimax framework for multiclass classification, which is applicable to general data including, in particular, imagery and other types of high-dimensional data. The framework consists of estimating a representation model that minimizes the fitting errors under a class of distortions of interest to an application, and deriving subsequently categorical information based on the estimated model. A variety of commonly used regression models, including lasso, elastic net and ridge regression, can be regarded as special cases that correspond to specific classes of distortions. Optimal decision rules are derived for this classification framework. By using kernel techniques the framework can account for nonlinearity in the input space. To demonstrate the power of the framework we consider a class of signal-dependent distortions and build a new family of classifiers as new special cases. This family of new methods-minimax classification with generalized multiplicative distortions-often outperforms the state-of-the-art classification methods such as the support vector machine in accuracy. Extensive experimental results on images, gene expressions and other types of data verify the effectiveness of the proposed framework. PMID- 26353054 TI - Hybridization Properties of RNA Containing 8-Methoxyguanosine and 8 Benzyloxyguanosine. AB - Modified nucleobase analogues can serve as powerful tools for changing physicochemical and biological properties of DNA or RNA. Guanosine derivatives containing bulky substituents at 8 position are known to adopt syn conformation of N-glycoside bond. On the contrary, in RNA the anti conformation is predominant in Watson-Crick base pairing. In this paper two 8-substituted guanosine derivatives, 8-methoxyguanosine and 8-benzyloxyguanosine, were synthesized and incorporated into oligoribonucleotides to investigate their influence on the thermodynamic stability of RNA duplexes. The methoxy and benzyloxy substituents are electron-donating groups, decreasing the rate of depurination in the monomers, as confirmed by N-glycoside bond stability assessments. Thermodynamic stability studies indicated that substitution of guanosine by 8-methoxy- or 8 benzyloxyguanosine significantly decreased the thermodynamic stability of RNA duplexes. Moreover, the presence of 8-substituted guanosine derivatives decreased mismatch discrimination. Circular dichroism spectra of modified RNA duplexes exhibited patterns typical for A-RNA geometry. PMID- 26353056 TI - Body Parts Dependent Joint Regressors for Human Pose Estimation in Still Images. AB - In this work, we address the problem of estimating 2d human pose from still images. Articulated body pose estimation is challenging due to the large variation in body poses and appearances of the different body parts. Recent methods that rely on the pictorial structure framework have shown to be very successful in solving this task. They model the body part appearances using discriminatively trained, independent part templates and the spatial relations of the body parts using a tree model. Within such a framework, we address the problem of obtaining better part templates which are able to handle a very high variation in appearance. To this end, we introduce parts dependent body joint regressors which are random forests that operate over two layers. While the first layer acts as an independent body part classifier, the second layer takes the estimated class distributions of the first one into account and is thereby able to predict joint locations by modeling the interdependence and co-occurrence of the parts. This helps to overcome typical ambiguities of tree structures, such as self-similarities of legs and arms. In addition, we introduce a novel data set termed FashionPose that contains over 7,000 images with a challenging variation of body part appearances due to a large variation of dressing styles. In the experiments, we demonstrate that the proposed parts dependent joint regressors outperform independent classifiers or regressors. The method also performs better or similar to the state-of-the-art in terms of accuracy, while running with a couple of frames per second. PMID- 26353057 TI - Depth Transfer: Depth Extraction from Video Using Non-Parametric Sampling. AB - We describe a technique that automatically generates plausible depth maps from videos using non-parametric depth sampling. We demonstrate our technique in cases where past methods fail (non-translating cameras and dynamic scenes). Our technique is applicable to single images as well as videos. For videos, we use local motion cues to improve the inferred depth maps, while optical flow is used to ensure temporal depth consistency. For training and evaluation, we use a Kinect-based system to collect a large data set containing stereoscopic videos with known depths. We show that our depth estimation technique outperforms the state-of-the-art on benchmark databases. Our technique can be used to automatically convert a monoscopic video into stereo for 3D visualization, and we demonstrate this through a variety of visually pleasing results for indoor and outdoor scenes, including results from the feature film Charade. PMID- 26353058 TI - Fast Exact Euclidean Distance (FEED): A New Class of Adaptable Distance Transforms. AB - A new unique class of foldable distance transforms of digital images (DT) is introduced, baptized: Fast exact euclidean distance (FEED) transforms. FEED class algorithms calculate the DT starting-directly from the definition or rather its inverse. The principle of FEED class algorithms is introduced, followed by strategies for their efficient implementation. It is shown that FEED class algorithms unite properties of ordered propagation, raster scanning, and independent scanning DT. Moreover, FEED class algorithms shown to have a unique property: they can be tailored to the images under investigation. Benchmarks are conducted on both the Fabbri et al. data set and on a newly developed data set. Three baseline, three approximate, and three state-of-the-art DT algorithms were included, in addition to two implementations of FEED class algorithms. It illustrates that FEED class algorithms i) provide truly exact Euclidean DT; ii) do no suffer from disconnected Voronoi tiles, which is a unique feature for non parallel but fast DT; iii) outperform any other approximate and exact Euclidean DT with its time complexity O(N), even after their optimization; and iv) are unequaled in that they can be adapted to the characteristics of the image class at hand. PMID- 26353059 TI - Information-Theoretic Dictionary Learning for Image Classification. AB - We present a two-stage approach for learning dictionaries for object classification tasks based on the principle of information maximization. The proposed method seeks a dictionary that is compact, discriminative, and generative. In the first stage, dictionary atoms are selected from an initial dictionary by maximizing the mutual information measure on dictionary compactness, discrimination and reconstruction. In the second stage, the selected dictionary atoms are updated for improved reconstructive and discriminative power using a simple gradient ascent algorithm on mutual information. Experiments using real data sets demonstrate the effectiveness of our approach for image classification tasks. PMID- 26353060 TI - Modeling Radiometric Uncertainty for Vision with Tone-Mapped Color Images. AB - To produce images that are suitable for display, tone-mapping is widely used in digital cameras to map linear color measurements into narrow gamuts with limited dynamic range. This introduces non-linear distortion that must be undone, through a radiometric calibration process, before computer vision systems can analyze such photographs radiometrically. This paper considers the inherent uncertainty of undoing the effects of tone-mapping. We observe that this uncertainty varies substantially across color space, making some pixels more reliable than others. We introduce a model for this uncertainty and a method for fitting it to a given camera or imaging pipeline. Once fit, the model provides for each pixel in a tone mapped digital photograph a probability distribution over linear scene colors that could have induced it. We demonstrate how these distributions can be useful for visual inference by incorporating them into estimation algorithms for a representative set of vision tasks. PMID- 26353061 TI - Pairwise Rotation Invariant Co-Occurrence Local Binary Pattern. AB - Designing effective features is a fundamental problem in computer vision. However, it is usually difficult to achieve a great tradeoff between discriminative power and robustness. Previous works shown that spatial co occurrence can boost the discriminative power of features. However the current existing co-occurrence features are taking few considerations to the robustness and hence suffering from sensitivity to geometric and photometric variations. In this work, we study the Transform Invariance (TI) of co-occurrence features. Concretely we formally introduce a Pairwise Transform Invariance (PTI) principle, and then propose a novel Pairwise Rotation Invariant Co-occurrence Local Binary Pattern (PRICoLBP) feature, and further extend it to incorporate multi-scale, multi-orientation, and multi-channel information. Different from other LBP variants, PRICoLBP can not only capture the spatial context co-occurrence information effectively, but also possess rotation invariance. We evaluate PRICoLBP comprehensively on nine benchmark data sets from five different perspectives, e.g., encoding strategy, rotation invariance, the number of templates, speed, and discriminative power compared to other LBP variants. Furthermore we apply PRICoLBP to six different but related applications-texture, material, flower, leaf, food, and scene classification, and demonstrate that PRICoLBP is efficient, effective, and of a well-balanced tradeoff between the discriminative power and robustness. PMID- 26353062 TI - Pseudo-Marginal Bayesian Inference for Gaussian Processes. AB - The main challenges that arise when adopting Gaussian process priors in probabilistic modeling are how to carry out exact Bayesian inference and how to account for uncertainty on model parameters when making model-based predictions on out-of-sample data. Using probit regression as an illustrative working example, this paper presents a general and effective methodology based on the pseudo-marginal approach to Markov chain Monte Carlo that efficiently addresses both of these issues. The results presented in this paper show improvements over existing sampling methods to simulate from the posterior distribution over the parameters defining the covariance function of the Gaussian Process prior. This is particularly important as it offers a powerful tool to carry out full Bayesian inference of Gaussian Process based hierarchic statistical models in general. The results also demonstrate that Monte Carlo based integration of all model parameters is actually feasible in this class of models providing a superior quantification of uncertainty in predictions. Extensive comparisons with respect to state-of-the-art probabilistic classifiers confirm this assertion. PMID- 26353063 TI - Scalable Nearest Neighbor Algorithms for High Dimensional Data. AB - For many computer vision and machine learning problems, large training sets are key for good performance. However, the most computationally expensive part of many computer vision and machine learning algorithms consists of finding nearest neighbor matches to high dimensional vectors that represent the training data. We propose new algorithms for approximate nearest neighbor matching and evaluate and compare them with previous algorithms. For matching high dimensional features, we find two algorithms to be the most efficient: the randomized k-d forest and a new algorithm proposed in this paper, the priority search k-means tree. We also propose a new algorithm for matching binary features by searching multiple hierarchical clustering trees and show it outperforms methods typically used in the literature. We show that the optimal nearest neighbor algorithm and its parameters depend on the data set characteristics and describe an automated configuration procedure for finding the best algorithm to search a particular data set. In order to scale to very large data sets that would otherwise not fit in the memory of a single machine, we propose a distributed nearest neighbor matching framework that can be used with any of the algorithms described in the paper. All this research has been released as an open source library called fast library for approximate nearest neighbors (FLANN), which has been incorporated into OpenCV and is now one of the most popular libraries for nearest neighbor matching. PMID- 26353064 TI - Spacetime Stereo and 3D Flow via Binocular Spatiotemporal Orientation Analysis. AB - This paper presents a novel approach to recovering estimates of 3D structure and motion of a dynamic scene from a sequence of binocular stereo images. The approach is based on matching spatiotemporal orientation distributions between left and right temporal image streams, which encapsulates both local spatial and temporal structure for disparity estimation. By capturing spatial and temporal structure in this unified fashion, both sources of information combine to yield disparity estimates that are naturally temporal coherent, while helping to resolve matches that might be ambiguous when either source is considered alone. Further, by allowing subsets of the orientation measurements to support different disparity estimates, an approach to recovering multilayer disparity from spacetime stereo is realized. Similarly, the matched distributions allow for direct recovery of dense, robust estimates of 3D scene flow. The approach has been implemented with real-time performance on commodity GPUs using OpenCL. Empirical evaluation shows that the proposed approach yields qualitatively and quantitatively superior estimates in comparison to various alternative approaches, including the ability to provide accurate multilayer estimates in the presence of (semi)transparent and specular surfaces. PMID- 26353065 TI - Spherical and Hyperbolic Embeddings of Data. AB - Many computer vision and pattern recognition problems may be posed as the analysis of a set of dissimilarities between objects. For many types of data, these dissimilarities are not euclidean (i.e., they do not represent the distances between points in a euclidean space), and therefore cannot be isometrically embedded in a euclidean space. Examples include shape dissimilarities, graph distances and mesh geodesic distances. In this paper, we provide a means of embedding such non-euclidean data onto surfaces of constant curvature. We aim to embed the data on a space whose radius of curvature is determined by the dissimilarity data. The space can be either of positive curvature (spherical) or of negative curvature (hyperbolic). We give an efficient method for solving the spherical and hyperbolic embedding problems on symmetric dissimilarity data. Our approach gives the radius of curvature and a method for approximating the objects as points on a hyperspherical manifold without optimisation. For objects which do not reside exactly on the manifold, we develop a optimisation-based procedure for approximate embedding on a hyperspherical manifold. We use the exponential map between the manifold and its local tangent space to solve the optimisation problem locally in the euclidean tangent space. This process is efficient enough to allow us to embed data sets of several thousand objects. We apply our method to a variety of data including time warping functions, shape similarities, graph similarity and gesture similarity data. In each case the embedding maintains the local structure of the data while placing the points in a metric space. PMID- 26353066 TI - 3D Object Recognition in Cluttered Scenes with Local Surface Features: A Survey. AB - 3D object recognition in cluttered scenes is a rapidly growing research area. Based on the used types of features, 3D object recognition methods can broadly be divided into two categories-global or local feature based methods. Intensive research has been done on local surface feature based methods as they are more robust to occlusion and clutter which are frequently present in a real-world scene. This paper presents a comprehensive survey of existing local surface feature based 3D object recognition methods. These methods generally comprise three phases: 3D keypoint detection, local surface feature description, and surface matching. This paper covers an extensive literature survey of each phase of the process. It also enlists a number of popular and contemporary databases together with their relevant attributes. PMID- 26353067 TI - Unsupervised Adaptation Across Domain Shifts by Generating Intermediate Data Representations. AB - With unconstrained data acquisition scenarios widely prevalent, the ability to handle changes in data distribution across training and testing data sets becomes important. One way to approach this problem is through domain adaptation, and in this paper we primarily focus on the unsupervised scenario where the labeled source domain training data is accompanied by unlabeled target domain test data. We present a two-stage data-driven approach by generating intermediate data representations that could provide relevant information on the domain shift. Starting with a linear representation of domains in the form of generative subspaces of same dimensions for the source and target domains, we first utilize the underlying geometry of the space of these subspaces, the Grassmann manifold, to obtain a 'shortest' geodesic path between the two domains. We then sample points along the geodesic to obtain intermediate cross-domain data representations, using which a discriminative classifier is learnt to estimate the labels of the target data. We subsequently incorporate non-linear representation of domains by considering a Reproducing Kernel Hilbert Space representation, and a low-dimensional manifold representation using Laplacian Eigenmaps, and also examine other domain adaptation settings such as (i) semi supervised adaptation where the target domain is partially labeled, and (ii) multi-domain adaptation where there could be more than one domain in source and/or target data sets. Finally, we supplement our adaptation technique with (i) fine-grained reference domains that are created by blending samples from source and target data sets to provide some evidence on the actual domain shift, and (ii) a multi-class boosting analysis to obtain robustness to the choice of algorithm parameters. We evaluate our approach for object recognition problems and report competitive results on two widely used Office and Bing adaptation data sets. PMID- 26353068 TI - Nonlinear Dynamic Projection for Noise Reduction of Dispersed Manifolds. AB - The search for a low-dimensional structure in high-dimensional data is one of the fundamental tasks in machine learning and pattern recognition. Manifold learning algorithms have recently emerged as alternatives to traditional linear dimension reduction techniques. In this paper, we propose a novel projection method that can be combined with any manifold learning methods to improve their dimension reduction performance when applied to high-dimensional data with a high level of noise. The method first builds a dispersion function that describes the distribution of dispersed manifold where the data lie. It then projects the noisy data onto a region wrapping the true manifold sufficiently close to it by applying a dynamical projection system associated with the constructed dispersion function. The effectiveness of the proposed projection method is validated by applying it to some real-world data sets with promising results. PMID- 26353069 TI - Phasic Triplet Markov Chains. AB - Hidden Markov chains have been shown to be inadequate for data modeling under some complex conditions. In this work, we address the problem of statistical modeling of phenomena involving two heterogeneous system states. Such phenomena may arise in biology or communications, among other fields. Namely, we consider that a sequence of meaningful words is to be searched within a whole observation that also contains arbitrary one-by-one symbols. Moreover, a word may be interrupted at some site to be carried on later. Applying plain hidden Markov chains to such data, while ignoring their specificity, yields unsatisfactory results. The Phasic triplet Markov chain, proposed in this paper, overcomes this difficulty by means of an auxiliary underlying process in accordance with the triplet Markov chains theory. Related Bayesian restoration techniques and parameters estimation procedures according to the new model are then described. Finally, to assess the performance of the proposed model against the conventional hidden Markov chain model, experiments are conducted on synthetic and real data. PMID- 26353070 TI - Probability Models for Open Set Recognition. AB - Real-world tasks in computer vision often touch upon open set recognition: multi class recognition with incomplete knowledge of the world and many unknown inputs. Recent work on this problem has proposed a model incorporating an open space risk term to account for the space beyond the reasonable support of known classes. This paper extends the general idea of open space risk limiting classification to accommodate non-linear classifiers in a multiclass setting. We introduce a new open set recognition model called compact abating probability (CAP), where the probability of class membership decreases in value (abates) as points move from known data toward open space. We show that CAP models improve open set recognition for multiple algorithms. Leveraging the CAP formulation, we go on to describe the novel Weibull-calibrated SVM (W-SVM) algorithm, which combines the useful properties of statistical extreme value theory for score calibration with one-class and binary support vector machines. Our experiments show that the W-SVM is significantly better for open set object detection and OCR problems when compared to the state-of-the-art for the same tasks. PMID- 26353071 TI - 3D printing antagonistic systems of artificial muscle using projection stereolithography. AB - The detailed mechanical design of a digital mask projection stereolithgraphy system is described for the 3D printing of soft actuators. A commercially available, photopolymerizable elastomeric material is identified and characterized in its liquid and solid form using rheological and tensile testing. Its capabilities for use in directly printing high degree of freedom (DOF), soft actuators is assessed. An outcome is the ~40% strain to failure of the printed elastomer structures. Using the resulting material properties, numerical simulations of pleated actuator architectures are analyzed to reduce stress concentration and increase actuation amplitudes. Antagonistic pairs of pleated actuators are then fabricated and tested for four-DOF, tentacle-like motion. These antagonistic pairs are shown to sweep through their full range of motion (~180 degrees ) with a period of less than 70 ms. PMID- 26353072 TI - Association of Predeployment Heart Rate Variability With Risk of Postdeployment Posttraumatic Stress Disorder in Active-Duty Marines. AB - IMPORTANCE: Disrupted autonomic nervous system functioning as measured by heart rate variability (HRV) has been associated with posttraumatic stress disorder (PTSD). It is not clear, however, whether reduced HRV before trauma exposure contributes to the risk for development of PTSD. OBJECTIVE: To examine whether HRV before combat deployment is associated with increased risk of a PTSD diagnosis after deployment when accounting for deployment-related combat exposure. DESIGN, SETTING, AND PARTICIPANTS: Between July 14, 2008, and May 24, 2012, active-duty Marines were assessed 1 to 2 months before a combat deployment and again 4 to 6 months after their return. The first phase of the Marine Resiliency Study (MRS-I) included 1415 male Marines, 59 of whom developed PTSD after deployment. Participants in the second phase of the Marine Resiliency Study (MRS-II) included 745 male Marines, 25 of whom developed PTSD after deployment. Analysis was conducted from November 25, 2013, to April 16, 2015. MAIN OUTCOMES AND MEASURES: Predeployment HRV was measured via finger photoplethysmography during a 5-minute period of rest. Frequency-domain measures of HRV were generated. Diagnosis of PTSD was determined using the Clinician-Administered PTSD Scale. RESULTS: After accounting for deployment-related combat exposure, lower HRV before deployment as measured by an increased low-frequency (LF) to high frequency (HF) ratio of HRV was associated with risk of PTSD diagnosis after deployment (combined MRS-I and MRS-II cohort meta-analysis odds ratio, 1.47; 95% CI, 1.10-1.98; P = .01). The prevalence of postdeployment PTSD was higher in participants with high predeployment LF:HF ratios (15.8% [6 of 38 participants]) compared with participants who did not have high LF:HF ratios (3.7% [78 of 2122 participants]). CONCLUSIONS AND RELEVANCE: This prospective longitudinal study provides initial and modest evidence that an altered state of autonomic nervous system functioning contributes to PTSD vulnerability, taking into account other key risk factors. If these findings are replicated, interventions that change autonomic nervous system function may open novel opportunities for prevention and treatment of PTSD. PMID- 26353073 TI - Predictors for a positive outcome of adapted clinical dry bed training in adolescents and adults with enuresis. AB - AIMS: Adapted Dry Bed Training (Adapted DBT) has been shown to be effective in therapy-resistant adolescents and adults with enuresis. Given the substantial impact of enuresis and the time-consuming nature of Adapted DBT, we investigated which patients benefited most from Adapted DBT. Therefore, we identified predictors for a successful treatment response to Adapted DBT in this population. METHODS: Retrospective cohort study in 907 consecutive patients, aged 11-42 years, subjected to in-hospital Adapted DBT in our Dry Bed Center between January 2003 and July 2013. Outcome was defined as treatment success after six months (primary outcome) and six weeks. Results of logistic regression analyses are presented in odds ratios and 95% confidence intervals. RESULTS: Predictors for a successful treatment response to Adapted DBT in adolescents and adults with enuresis after six months are: gender (female), initial degree of enuresis (mild: 0-3 nights/week), current diaper use, never used anticholinergics in the past, and degree of enuresis six weeks after training. Predictors for successful treatment response after six weeks are: gender and initial degree of enuresis only. LIMITATION: The low explained variance of our model, showing that many other factors, not included in our study, could be of interest in the prediction of success. CONCLUSIONS: Several factors that predicted a successful treatment response of Adapted DBT after six weeks and six months were identified. However, the low explained variance of our model suggests that other non-identified factors are also important in predicting outcome. Neurourol. Urodynam. 35:1006 1010, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26353074 TI - Chanarin Dorfman syndrome: a case report with novel nonsense mutation. AB - Chanarin Dorfman syndrome (CDS) is a very rare neutral lipid metabolism disorder with multisystem involvement. It is inherited as an autosomal recessive manner. It is characterized with congenital ichthyosiform erythroderma and involvement of liver, muscle, and central nervous system. Demonstration of lipid vacuoles in neutrophils from peripheral blood smears in patients with ichthyosiform erythroderma leads to the diagnosis. We report a novel ABHD5 truncating variant in a twenty nine month old female child, who presented with icthyosiform erythroderma. PMID- 26353075 TI - Splenectomy enhances the therapeutic effect of adipose tissue-derived mesenchymal stem cell infusion on cirrhosis rats. AB - BACKGROUND & AIMS: Clinical studies suggest that splenectomy improves liver function in cirrhotic patients, but the influence of splenectomy on stem cell transplantation is poorly understood. This study investigated the effect of splenectomy on stem cell infusion and elucidated its mechanism. METHODS: Rat adipose tissue-derived mesenchymal stem cells were infused into cirrhosis rats with or without splenectomy, followed by the assessment of the in vivo distribution of stem cells and pathological changes. Stromal cell-derived factor 1 and hepatocyte growth factor expression were also investigated in splenectomized cirrhosis patients and rats. RESULTS: Splenectomy, prior to cell infusion, improved liver function and suppressed fibrosis progression more efficiently than cell infusion alone in the experimental cirrhosis model. Stromal cell-derived factor-1 and hepatocyte growth factor levels after splenectomy were increased in patients and rats. These upregulated cytokines significantly facilitated stem cell motility, migration and proliferation in vitro. C-X-C chemokine receptor type 4 neutralization weakened the promotion of cell migration by these cytokines. The infused cells integrated into liver fibrosis septa and participated in regeneration more efficiently in splenectomized rats. Direct coculture with stem cells led to inhibition of hepatic stellate cell proliferation. In addition, hepatocyte growth factor induced hepatic stellate cell apoptosis via the c-jun N-terminal kinase-p53 pathway. CONCLUSIONS: Splenectomy prior to cell infusion enhanced the therapeutic effect of stem cells on cirrhosis, which involved upregulation of stromal cell-derived factor-1 and hepatocyte growth factor after splenectomy. PMID- 26353076 TI - Secular trends in Acinetobacter baumannii resistance in respiratory and blood stream specimens in the United States, 2003 to 2012: A survey study. AB - BACKGROUND: Acinetobacter baumannii (AB) has evolved a variety of resistance mechanisms and exhibits unpredictable susceptibility patterns, making it difficult to select empiric therapy. OBJECTIVE: To examine US secular trends in the resistance of AB in respiratory infections and blood stream infections (BSI) to antimicrobial agents whose effectiveness is supported in the literature DESIGN: Survey. METHODS: We analyzed 3 time periods (2003-2005, 2006-2008, 2009 2012) in Eurofins' The Surveillance Network for resistance of AB to the following antimicrobials: carbapenems (imipenem, meropenem, doripenem), aminoglycosides (tobramycin, amikacin), tetracyclines (minocycline, doxycycline), polymyxins (colistin, polymyxin B), ampicillin-sulbactam, and trimethoprim-sulfamethoxazole. Resistance to >=3 drug classes defined multidrug resistance (MDR). RESULTS: We identified 39,320 AB specimens (81.1% respiratory, 18.9% BSI). The highest prevalence of resistance was to doripenem (90.3%) followed by trimethoprim sulfamethoxazole (55.3%), and the lowest to colistin (5.3%). Resistance to carbapenems (21.0% in 2003-2005 and 47.9% in 2009-2012) and colistin (2.8% in 2006-2008 to 6.9% in 2009-2012) more than doubled. Prevalence of MDR AB rose from 21.4% in 2003 to 2005 to 33.7% in 2006 to 2008, and remained stable at 35.2% in 2009 to 2012. In contrast, resistance to minocycline diminished from 56.5% (2003 2005) to 30.5% (2009-2012). MDR organisms were most frequent in nursing homes (46.5%), followed by general ward (29.2%), intensive care unit (28.7%), and outpatient setting (26.2%). CONCLUSIONS: Resistance rates among AB to such last resort antimicrobials as carbapenems and colistin are on the rise, whereas that to minocycline has declined. Nursing homes are a reservoir of resistant AB. These trends should inform not only empiric treatment of serious infections, but also approaches to infection control. PMID- 26353077 TI - Gene expression profile in newborn rat lungs after two days of recovery of mechanical ventilation. AB - BACKGROUND: Preterm infants having immature lungs often require respiratory support, potentially leading to bronchopulmonary dysplasia (BPD). Conventional BPD rodent models based on mechanical ventilation (MV) present outcome measured at the end of the ventilation period. A reversible intubation and ventilation model in newborn rats recently allowed discovering that different sets of genes modified their expression related to time after MV. In a newborn rat model, the expression profile 48 h after MV was analyzed with gene arrays to detect potentially interesting candidates with an impact on BPD development. METHODS: Rat pups were injected P4-5 with 2 mg/kg lipopolysaccharide (LPS). One day later, MV with 21 or 60% oxygen was applied during 6 h. Animals were sacrified 48 h after end of ventilation. Affymetrix gene arrays assessed the total gene expression profile in lung tissue. RESULTS: In fully treated animals (LPS + MV + 60% O(2)) vs. controls, 271 genes changed expression significantly. All modified genes could be classified in six pathways: tissue remodeling/wound repair, immune system and inflammatory response, hematopoiesis, vasodilatation, and oxidative stress. Major alterations were found in the MMP and complement system. CONCLUSION: MMPs and complement factors play a central role in several of the pathways identified and may represent interesting targets for BPD treatment/prevention.Bronchopulmonary dysplasia (BPD) is a chronic lung disease occurring in ~30% of preterm infants born less than 30 wk of gestation (1). Its main risk factors include lung immaturity due to preterm delivery, mechanical ventilation (MV), oxygen toxicity, chorioamnionitis, and sepsis. The main feature is an arrest of alveolar and capillary formation (2). Models trying to decipher genes involved in the pathophysiology of BPD are mainly based on MV and oxygen application to young mammals with immature lungs of different species (3). In newborn rodent models, analyses of lung structure and gene and protein expression are performed for practical reasons directly at the end of MV (4,5,6). However, later appearing changes of gene expression might also have an impact on lung development and the evolution towards BPD and cannot be discovered by such models. Recently, we developed a newborn rat model of MV using an atraumatic (orotracheal) intubation technique that allows the weaning of the newborn animal off anesthesia and MV, the extubation to spontaneous breathing, and therefore allows the evaluation of effects of MV after a ventilation-free period of recovery (7). Indeed, applying this concept of atraumatic intubation by direct laryngoscopy, we recently were able to show significant differences between gene expression changes appearing directly after MV compared to those measured after a ventilation-free interval of 48 h. Immediately after MV, inflammation-related genes showed a transitory modified expression, while another set of more structurally related genes changed their expression only after a delay of 2 d (7). Lung structure, analyzed by conventional 2D histology and also by 3D reconstruction using synchrotron x-ray tomographic microscopy revealed, 48 h after end of MV, a reduced complexity of lung architecture compared to the nonventilated rat lungs, similar to the typical findings in BPD. To extend these observations about late gene expression modifications, we performed with a similar model a full gene expression profile of lung tissue 48 h after the end of MV with either room air or 60% oxygen. Essentially, we measured changes in the expression of genes related to the MMPs and complement system which played a role in many of the six identified mostly affected pathways. PMID- 26353078 TI - Knowledge of Native Protein-Protein Interfaces Is Sufficient To Construct Predictive Models for the Selection of Binding Candidates. AB - Selection of putative binding poses is a challenging part of virtual screening for protein-protein interactions. Predictive models to filter out binding candidates with the highest binding affinities comprise scoring functions that assign a score to each binding pose. Existing scoring functions are typically deduced by collecting statistical information about interfaces of native conformations of protein complexes along with interfaces of a large generated set of non-native conformations. However, the obtained scoring functions become biased toward the method used to generate the non-native conformations, i.e., they may not recognize near-native interfaces generated with a different method. The present study demonstrates that knowledge of only native protein-protein interfaces is sufficient to construct well-discriminative predictive models for the selection of binding candidates. Here we introduce a new scoring method that comprises a knowledge-based potential called KSENIA deduced from structural information about the native interfaces of 844 crystallographic protein-protein complexes. We derive KSENIA using convex optimization with a training set composed of native protein complexes and their near-native conformations obtained using deformations along the low-frequency normal modes. As a result, our knowledge-based potential has only marginal bias toward a method used to generate putative binding poses. Furthermore, KSENIA is smooth by construction, which allows it to be used along with rigid-body optimization to refine the binding poses. Using several test benchmarks, we demonstrate that our method discriminates well native and near-native conformations of protein complexes from non-native ones. Our methodology can be easily adapted to the recognition of other types of molecular interactions, such as protein-ligand, protein-RNA, etc. KSENIA will be made publicly available as a part of the SAMSON software platform at https://team.inria.fr/nano-d/software . PMID- 26353079 TI - Short Communication: Reassessing the Origin of the HIV-1 CRF02_AG Lineages Circulating in Brazil. AB - HIV-1 CRF02_AG is responsible for at least 8% of the HIV-1 infections worldwide and is distributed mainly in West Africa. CRF02_AG has recently been reported in countries where it is not native, including Brazil. In a previous study including 10 CRF02_AG Brazilian samples, we found at least four independent introductions and two autochthonous transmission networks of this clade in Brazil. As more CRF02_AG samples have been identified in Brazil, we performed a new phylogeographic analysis using a larger dataset than before. A total of 20 Brazilian (18 from Rio de Janeiro and two from Sao Paulo) and 1,485 African HIV-1 CRF02_AG pol sequences were analyzed using maximum likelihood (ML). The ML tree showed that the Brazilian sequences were distributed in five different lineages. The Bayesian phylogeographic analysis of the Brazilian and their most closely related African sequences (n = 212) placed the origin of all Brazilian lineages in West Africa, probably Ghana, Senegal, and Nigeria. Two monophyletic clades were identified, comprising only sequences from Rio de Janeiro, and their date of origin was estimated at around 1985 (95% highest posterior density: 1979-1992). These results support the existence of at least five independent introductions of the CRF02_AG lineage from West Africa into Brazil and further indicate that at least two of these lineages have been locally disseminated in the Rio de Janeiro state over the past 30 years. PMID- 26353080 TI - Circadian Rhythms in Socializing Propensity. AB - Using large-scale interaction data from a virtual world, we show that people's propensity to socialize (forming new social connections) varies by hour of the day. We arrive at our results by longitudinally tracking people's friend-adding activities in a virtual world. Specifically, we find that people are most likely to socialize during the evening, at approximately 8 p.m. and 12 a.m., and are least likely to do so in the morning, at approximately 8 a.m. Such patterns prevail on weekdays and weekends and are robust to variations in individual characteristics and geographical conditions. PMID- 26353081 TI - Six years' experience in ovum donation using vitrified oocytes: report of cumulative outcomes, impact of storage time, and development of a predictive model for oocyte survival rate. AB - OBJECTIVE: To describe the clinical outcomes achieved after 6 years' experience in ovum donation conducted with vitrified oocytes; to attempt to find predictors of survival; and to provide information about the probability of having a baby according to the number of oocytes consumed. DESIGN: Retrospective, observational study. SETTING: Private university-affiliated in vitro fertilization center. PATIENT(S): Recipients of vitrified oocytes (January 2007-March 2013), including all the warming procedures (n = 3,610) and all the donations made during the same period (n = 3,467). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Survival rate per warming procedure, cumulative delivery rates (CDR) per single donation cycle, oocyte-to-baby rate, and cumulative live birth rate (CLBR) per oocyte consumed. RESULT(S): Oocyte survival rate was 90.4%. It was not possible to develop a predictive model for survival owing to the lack of prognostic value of the studied variables. Implantation, clinical, and ongoing pregnancy rates per donation cycle were 39.0% (95% confidence interval [CI], 37.8-40.5), 48.4% (95% CI, 46.7-50.1), and 39.9% (95% CI, 38.3-41.5), respectively. Statistical differences were found when comparing blastocysts versus day 3 ETs (42.5%; 95% CI, 40.4-45.2 vs. 37.5%; 95% CI, 35.3-39.7 ongoing pregnancy rate). The CDR/donation cycle, including cryotransfers, was 78.8% (95% CI, 73.5-84.1). The oocyte-to-baby rate was 6.5%. CLBR increased progressively according to the number of oocytes consumed. CONCLUSION(S): We provide detailed information about the high efficiency of using vitrified/warmed oocytes. There is currently no way of estimating donors' oocytes survival when considering baseline characteristics, storage time, or controlled ovarian stimulation parameters. The probability of achieving a baby using vitrified oocytes increases progressively with the number of oocytes consumed. PMID- 26353082 TI - Stomatal responses to vapour pressure deficit are regulated by high speed gene expression in angiosperms. AB - Plants dynamically regulate water use by the movement of stomata on the surface of leaves. Stomatal responses to changes in vapour pressure deficit (VPD) are the principal regulator of daytime transpiration and water use efficiency in land plants. In angiosperms, stomatal responses to VPD appear to be regulated by the phytohormone abscisic acid (ABA), yet the origin of this ABA is controversial. After a 20 min exposure of plants, from three diverse angiosperm species, to a doubling in VPD, stomata closed, foliar ABA levels increased and the expression of the gene encoding the key, rate-limiting carotenoid cleavage enzyme (9-cis epoxycarotenoid dioxygenase, NCED) in the ABA biosynthetic pathway was significantly up-regulated. The NCED gene was the only gene in the ABA biosynthetic pathway to be up-regulated over the short time scale corresponding to the response of stomata. The closure of stomata and rapid increase in foliar ABA levels could not be explained by the release of ABA from internal stores in the leaf or the hydrolysis of the conjugate ABA-glucose ester. These results implicate an extremely rapid de novo biosynthesis of ABA, mediated by a single gene, as the means by which angiosperm stomata respond to natural changes in VPD. PMID- 26353083 TI - Fluorescence fluctuation of an antigen-antibody complex: circular dichroism, FCS and smFRET of enhanced GFP and its antibody. AB - The structure and dynamics of an antigen-antibody complex are monitored by circular dichroism (CD) spectroscopy, fluorescence correlation spectroscopy (FCS) and single molecule FRET (smFRET). In this work, the antigen is enhanced GFP (EGFP) and the antibody is anti-EGFP VHH-His6. From FCS measurements, the hydrodynamic radius (rH) of EGFP and its antibody (VHH-His6) is found to be 24 +/ 2 A and 18 +/- 2 A, respectively. For the antigen-antibody complex (EGFP:anti EGFP VHH-His6), rH is 41 +/- 3 A. CD spectra indicate that the addition of guanidium hydrochloride (GdnHCl) causes unfolding of the antigen, its antibody and their complex, and a consequent increase in size is observed from FCS data. smFRET between EGFP (donor, D) and Alexa 594 (acceptor, A) bound to anti-EGFP VHH His6 reveals a time dependent fluctuation in donor-acceptor distances. This suggests that the structure of the antigen-antibody complex is dynamic in nature and is not rigid. PMID- 26353085 TI - Reply. PMID- 26353084 TI - Prognostic significance of Epstein-Barr virus DNA detection in pretreatment serum in diffuse large B-cell lymphoma. AB - It is still a matter of debate whether detection of Epstein-Barr virus (EBV) DNA in pretreatment serum has clinical implications for diffuse large B-cell lymphoma. For this study, we measured EBV DNA load in pretreatment serum from 127 diffuse large B-cell lymphoma patients without any underlying immunodeficiency to evaluate its effects on clinical manifestations and prognosis. Anthracycline based chemotherapy in combination with rituximab was given as initial therapy for 119 patients (94%). Epstein-Barr virus DNA was detected in 15 patients (12%), who were older (P = 0.005) and tended to be at a more advanced disease stage (P = 0.053). They showed significantly worse progression-free survival (PFS) and overall survival (OS) than other patients (P < 0.001 each). This effect remained significant (P = 0.004 and P = 0.027, respectively) after adjustment for age, lactate dehydrogenase, performance status, stage, and extranodal sites. The status of EBV-encoded small RNA in situ hybridization was known for 123 patients; 6 of 8 positive patients (75%) and 9 of 115 negative patients (8%) had detectable EBV DNA in pretreatment serum. While patients positive for EBV-encoded small RNA had significantly worse PFS and OS than negative patients (P = 0.001 and P = 0.029, respectively), EBV DNA detection in pretreatment serum was associated with poorer PFS and OS even for the 115 patients negative for EBV-encoded small RNA (P < 0.001 each). These findings suggest that EBV DNA detection in pretreatment serum may have an adverse prognostic impact for patients with diffuse large B cell lymphoma. PMID- 26353086 TI - Leaf Colour as a Signal of Chemical Defence to Insect Herbivores in Wild Cabbage (Brassica oleracea). AB - Leaf colour has been proposed to signal levels of host defence to insect herbivores, but we lack data on herbivory, leaf colour and levels of defence for wild host populations necessary to test this hypothesis. Such a test requires measurements of leaf spectra as they would be sensed by herbivore visual systems, as well as simultaneous measurements of chemical defences and herbivore responses to leaf colour in natural host-herbivore populations. In a large-scale field survey of wild cabbage (Brassica oleracea) populations, we show that variation in leaf colour and brightness, measured according to herbivore spectral sensitivities, predicts both levels of chemical defences (glucosinolates) and abundance of specialist lepidopteran (Pieris rapae) and hemipteran (Brevicoryne brassicae) herbivores. In subsequent experiments, P. rapae larvae achieved faster growth and greater pupal mass when feeding on plants with bluer leaves, which contained lower levels of aliphatic glucosinolates. Glucosinolate-mediated effects on larval performance may thus contribute to the association between P. rapae herbivory and leaf colour observed in the field. However, preference tests found no evidence that adult butterflies selected host plants based on leaf coloration. In the field, B. brassicae abundance varied with leaf brightness but greenhouse experiments were unable to identify any effects of brightness on aphid preference or performance. Our findings suggest that although leaf colour reflects both levels of host defences and herbivore abundance in the field, the ability of herbivores to respond to colour signals may be limited, even in species where performance is correlated with leaf colour. PMID- 26353088 TI - Ensuring a unified and cross-cultural nursing language system: the challenge faced by nursing terminology development. PMID- 26353087 TI - Mapping of Bancroftian Filariasis in Cameroon: Prospects for Elimination. AB - BACKGROUND: Lymphatic filariasis (LF) is one of the most debilitating neglected tropical diseases (NTDs). It still presents as an important public health problem in many countries in the tropics. In Cameroon, where many NTDs are endemic, only scant data describing the situation regarding LF epidemiology was available. The aim of this study was to describe the current situation regarding LF infection in Cameroon, and to map this infection and accurately delineate areas where mass drug administration (MDA) was required. METHODOLOGY: The endemicity status and distribution of LF was assessed in eight of the ten Regions of Cameroon by a rapid-format card test for detection of W. bancrofti antigen (immunochromatographic test, ICT). The baseline data required to monitor the effectiveness of MDA was collected by assessing microfilariaemia in nocturnal calibrated thick blood smears in sentinel sites selected in the health districts where ICT positivity rate was >= 1%. PRINCIPAL FINDINGS: Among the 120 health districts visited in the eight Regions during ICT survey, 106 (88.3%) were found to be endemic for LF (i.e. had ICT positivity rate >= 1%), with infection rate from 1.0% (95% CI: 0.2-5.5) to 20.0% (95% CI: 10-30). The overall infection rate during the night blood survey was 0.11% (95% CI: 0.08-0.16) in 11 health districts out of the 106 surveyed; the arithmetic mean for microfilaria density was 1.19 mf/ml (95% CI: 0.13-2.26) for the total population examined. CONCLUSION/SIGNIFICANCE: ICT card test results showed that LF was endemic in all the Regions and in about 90% of the health districts surveyed. All of these health districts qualified for MDA (i.e. ICT positivity rate >= 1%). Microfilariaemia data collected as part of this study provided the national program with baseline data (sentinel sites) necessary to measure the impact of MDA on the endemicity level and transmission of LF important for the 2020 deadline for global elimination. PMID- 26353089 TI - [Factors associated with the quality of prenatal care: an approach to premature birth]. AB - OBJECTIVE: To assess the quality of prenatal care in mothers with premature and term births and identify maternal and gestational factors associated with inadequate prenatal care. METHOD: Cross-sectional study collecting data with the pregnant card, hospital records and interviews with mothers living in Maringa-PR. Data were collected from 576 mothers and their born alive infants who were attended in the public service from October 2013 to February 2014, using three different evaluation criteria. The association of prenatal care quality with prematurity was performed by univariate analysis and occurred only at Kessner criteria (CI=1.79;8.02). RESULTS: The indicators that contributed most to the inadequacy of prenatal care were tests of hemoglobin, urine, and fetal presentation. After logistic regression analysis, maternal and gestational variables associated to inadequate prenatal care were combined prenatal (CI=2.93;11.09), non-white skin color (CI=1.11;2.51); unplanned pregnancy (CI=1.34;3.17) and multiparity (CI=1.17;4.03). CONCLUSION: Prenatal care must follow the minimum recommended protocols, more attention is required to black and brown women, multiparous and with unplanned pregnancies to prevent preterm birth and maternal and child morbimortality. PMID- 26353090 TI - [Effect of reducing sensory and environmental stimuli during hospitalized premature infant sleep]. AB - OBJECTIVE: To compare the total sleep time of premature infant in the presence or absence of reducing sensory and environmental stimuli in the neonatal unit. METHOD: Longitudinal study in a Neonatal Intermediate Care Unit of a public hospital in Sao Paulo. The sample consisted of 13 premature infants. We used polysomnograph and unstructured observation for data collection. We analyzed 240 and 1200 minutes corresponding to the periods of the presence and absence of environmental management, respectively. Data were compared in proportion to the total sleep time in the two moments proposed by the study. RESULTS: The total sleep time in periods without environmental management was on average 696.4 (+/- 112.1) minutes and with management 168.5 (+/- 27.9) minutes, proportionally premature infant slept an average of 70.2% during periods with no intervention and 58.0% without management (p=0.002). CONCLUSION: Reducing stimulation and handling of premature infant environment periods was effective to provide greater total sleep time. PMID- 26353091 TI - [Understanding child neglect in a gender context: a study performed in a Brazilian city]. AB - OBJECTIVE: To describe the phenomenon of child neglect and understand it in a gender context. METHOD: Retrospective, quantitative, and exploratory study that analyzed reports of violence by a child and adolescent protection network in a Brazilian city. The theoretical and methodological basis applied was TIPESC (Theory of Nursing Praxical Intervention in Collective Health), with a gender emphasis. RESULTS: Neglect of children under the age of ten represents more than half the reports received over all the years studied; more boys than girls suffered neglect and 41.4% of the reports of neglect involved children under than age of three; women were identified as being solely responsible in 67.9%, and as accessories in 17.3% of the incidents reported. CONCLUSION: Child neglect is a complex matter, the gender subordinate status inflicted on these children and their mothers who are responsible for their care underscore the social vulnerability of this group. PMID- 26353092 TI - [Skin cancer in rural workers: nursing knowledge and intervention]. AB - OBJECTIVE: To identify the exposure of rural workers to the sun's ultraviolet radiation and pesticides; to identify previous cases of skin cancer; and to implement clinical and communicative nursing actions among rural workers with a previous diagnosis of skin cancer. METHOD: Observational-exploratory study conducted with rural workers exposed to ultraviolet radiation and pesticides in a rural area in the extreme south of Brazil. A clinical judgment and risk communication model properly adapted was used to develop interventions among workers with a previous history of skin cancer. RESULTS: A total of 123 (97.7%) workers were identified under conditions of exposure to the sun's ultraviolet radiation and pesticides; seven (5.4%) were identified with a previous diagnosis of skin cancer; four (57.1%) of these presented potential skin cancer lesions. CONCLUSION: This study's results enabled clarifying the combination of clinical knowledge and risk communication regarding skin cancer to rural workers. PMID- 26353093 TI - [Factors influencing Intensive Care Units nurses in end-of-life decisions]. AB - OBJECTIVE: To identify the factors that influence the Intensive Care Unit nurse in the decision-making process in end-of-life situations. METHOD: Ethnographic case study, which used the theoretical framework of medical anthropology. Data were collected through semi-structured interviews with 10 nurses. RESULTS: The inductive thematic analysis enabled us to identify four themes:The cultural context of the Intensive Care Unit: decision-making in situations of end-of-life; Beliefs and subjectivity of care in end-of-life situations; Professional experience and context characteristics of end-of-life care situations; and Humanization practices in end-of-life situations: the patient and family centered care. CONCLUSION: Professional maturity, the ability to transmit information and the ability to negotiate are directly related to the inclusion of nurses in the decision-making process. PMID- 26353094 TI - [Nursing Actions in practicing inpatient advocacy in a Burn Unit]. AB - OBJECTIVE: Understanding nursing actions in the practice of inpatient advocacy in a burn unit. METHOD: A single and descriptive case study, carried out with nurses working in a referral burn center in southern Brazil. Data were collected through focus group technique, between February and March 2014, in three meetings. Data was analysed through discursive textual analysis. RESULTS: Three emerging categories were identified, namely: (1) instructing the patient; (2) protecting the patient; and (3) ensuring the quality of care. CONCLUSIONS: This study identified that the nurses investigated exercised patient advocacy and that the recognition of their actions is an advance for the profession, contributing to the autonomy of nurses and the effectiveness of patients' rights and social justice. PMID- 26353095 TI - [Cultural singularities: indigenous elderly access to Public Health Service]. AB - OBJECTIVE: Describing how Kaingang seniors and their primary caregivers experience access to public health services. METHOD: A qualitative study guided by ethnography, conducted with 28 elderly and 19 caregivers. Data were collected between November 2010 and February 2013 through interviews and participative observation analyzed by ethnography. RESULTS: The study revealed the benefits and difficulties of the elderly access to health services, the facility to obtain health care resources such as appointments, medications and routine procedures, and the difficulties such as special assistance service problems and delays in the dispatching process between reference services. CONCLUSION: The importance of knowing and understanding the cultural specificities of the group in order to offer greater opportunities for the elderly access to health services was reinforced. PMID- 26353096 TI - [The quality and characteristics of sleep of hypertensive patients]. AB - OBJECTIVE: Analyzing the quality of sleep of hypertensive patients registered in the national registration system and monitoring of hypertensive patients. METHODS: A cross-sectional study of quantitative and descriptive analyses with 280 hypertensive patients registered in the National Program of Hypertension and Diabetes of the Federal Government in the months from August to October 2011. Questionnaires were used which allowed for tracking sociodemographic data on hypertension and Pittsburgh Sleep Quality Index (PSQI). RESULTS: The prevalence of poor sleep quality among respondents (156 hypertensive patients) and high rates of using medication for sleeping (106 hypertensive patients) was observed. Other relevant data refers to the quality of sleep among hypertensive patients using sleep medication compared to those who do not use it (p<=0.01). CONCLUSION: Individuals with high blood pressure have a negative association with sleep quality. PMID- 26353097 TI - [Family health nursing care: weaknesses and strengths in the Unified Health System]. AB - OBJECTIVE: To analyze the weaknesses and strengths of nursing care in the Family Health Strategy and its interfaces with the Unified Health System network. METHOD: A qualitative study performed by means of semi-structured interviews and systematic observations, with the participation of a nursing team of 15 people from October of 2012 to January of 2013. RESULTS: Strengths that were emphasized: the nurse's versatility in conducting users within the unit and the health system, therefore directly acting upon access to these services. The nurse is the main subject that participates in the care processes for the person, family and social groups. Weaknesses that were highlighted: fragile embracement and low resolution of users' and families' problems. CONCLUSION: The nursing care process in health units still lacks collective articulation, involvement of the team, and decentralization of the decisions. PMID- 26353098 TI - [Family Health Strategy professionals' view on the effects of Hansen's disease training]. AB - OBJECTIVE: Evaluating how professionals of family health teams from three municipalities of Pernambuco perceive and interpret the effects of Hansen's disease training. METHODS: A qualitative study using the perspective of Habermas. Six focus groups, totaling 33 nurses and 22 doctors were formed. The guide consisted of: reactions to training, learning, transfer of knowledge and organizational results. RESULTS: There were recurrent positive opinions on instructor performance, course materials, and an alert attitude to the occurrence of cases; the negative points were about lack of practical teaching, a lot of information in a short period of time and little emphasis on basic content. Low perceived self-efficacy and low locus of control, ambiguity, conflict of skills and the lack of support for the learning application. Nurses showed greater dissatisfaction with the organizational support. CONCLUSION: The low effectiveness of training reveals the need to negotiate structured training from work problematization, considering performance conditions. PMID- 26353099 TI - [Adherence to nutritional recommendations and sociodemographic variables in patients with diabetes mellitus]. AB - OBJECTIVE: To determine if there is a relationship between adherence to nutritional recommendations and sociodemographic variables in Brazilian patients with type 2 diabetes mellitus. METHODS: Cross-sectional observational study using a stratified random sample of 423 individuals. The Food Frequency Questionnaire (FFQ) was used, and the Fisher's exact test was applied with 95% confidence interval (p<0.05). RESULTS: Of the 423 subjects, 66.7% were women, mean age of 62.4 years (SD = 11.8), 4.3 years of schooling on average (SD = 3.6) and family income of less than two minimum wages. There was association between the female gender and adherence to diet with adequate cholesterol content (OR: 2.03; CI: 1.23; 3.34), between four and more years of education and adherence to fractionation of meals (OR: 1 92 CI: 1.19; 3.10), and income of less than two minimum wages and adherence to diet with adequate cholesterol content (OR: 1.74; CI: 1.03, 2.95). CONCLUSION: Adherence to nutritional recommendations was associated with the female gender, more than four years of education and family income of less than two minimum wages. PMID- 26353100 TI - [The sign of the Cross of Andreas in the iris and Diabetes Mellitus: a longitudinal study]. AB - OBJECTIVE: To compare the development of diabetes mellitus in subjects with and without the sign of the Cross of Andreas in the iris over a period of four years. METHOD: A prospective, descriptive study of quantitative approach. This cohort study had 91 patients without the disease, with and without the signal. The monitoring was conducted by means of the records in medical charts. RESULTS: At the end of the research, 28.2% of the group with the sign of the Cross of Andreas was diagnosed with diabetes and 56.5% had two or more episodes of impaired glucose tolerance. In the group without the sign, 4.4% was diagnosed with the disease and 24.5% had two or more episodes of glucose intolerance. There was a statistically significant difference between the groups regarding the development of the disease and glucose intolerance. CONCLUSION: The group with the Cross of Andreas developed more glucose intolerance and diabetes than the group without the sign. PMID- 26353101 TI - [The nurse in the management of materials in teaching hospitals]. AB - OBJECTIVE: To present the nurse's integration within materials management of six teaching hospitals of Parana - Brazil, and to describe the activities performed by nurses within this process. METHOD: A study of a qualitative approach and descriptive nature, conducted in teaching hospitals in Parana, between June and August of 2013. The data collection was conducted through semi-structured interviews with eight nurses who worked in materials management; data were analyzed using content analysis. RESULTS: These showed that nurses perform ten categories of activities, distributed into four of the five steps of the materials management process. CONCLUSION: The nurse, in performing of these activities, in addition to favoring the development of participative management, contributes to the organization, planning, and the standardization of the hospital supply process, giving greater credibility to the work with professionals who use the materials, and to the suppliers. PMID- 26353102 TI - [Knowledge of the Portuguese population on Basic Life Support and availability to attend training]. AB - OBJECTIVE: To evaluate the level of knowledge and the availability of the Portuguese population to attend training in Basic Life Support (BLS) and identify factors related to their level of knowledge about BLS. METHOD: Observational study including 1,700 people who responded to a questionnaire containing data on demography, profession, training, interest in training and knowledge about BLS. RESULTS: Among 754 men and 943 women, only 17.8% (303) attended a course on BLS, but 95.6% expressed willingness to carry out the training. On average, they did not show good levels of knowledge on basic life support (correct answers in 25.9 +/- 11.5 of the 64 indicators). Male, older respondents who had the training and those who performed BLS gave more correct answers, on average (p<0.01). CONCLUSION: The skill levels of the Portuguese population are low, but people are available for training, hence it is important to develop training courses and practice to improve their knowledge. PMID- 26353103 TI - Effects of web-based electrocardiography simulation on strategies and learning styles. AB - OBJECTIVE: To identify the association between the use of web simulation electrocardiography and the learning approaches, strategies and styles of nursing degree students. METHOD: A descriptive and correlational design with a one-group pretest-posttest measurement was used. The study sample included 246 students in a Basic and Advanced Cardiac Life Support nursing class of nursing degree. RESULTS: No significant differences between genders were found in any dimension of learning styles and approaches to learning. After the introduction of web simulation electrocardiography, significant differences were found in some item scores of learning styles: theorist (p < 0.040), pragmatic (p < 0.010) and approaches to learning. CONCLUSION: The use of a web electrocardiogram (ECG) simulation is associated with the development of active and reflexive learning styles, improving motivation and a deep approach in nursing students. PMID- 26353104 TI - [Assessment of the teaching-learning process in students of the health area: cardiopulmonary resuscitation maneuvers]. AB - OBJECTIVE: To evaluate the skills and knowledge of undergraduate students in the health area on cardiopulmonary resuscitation maneuvers with the use of an automatic external defibrillator. METHOD: The evaluation was performed in three different stages of the teaching-learning process. A theoretical and practical course was taught and the theoretical classes included demonstration. The evaluation was performed in three different stages of the teaching-learning process. Two instruments were applied to evaluate the skills (30-items checklist) and knowledge (40-questions written test). The sample comprised 84 students. RESULTS: After the theoretical and practical course, an increase was observed in the number of correct answers in the 30-items checklist and 40-questions written test. CONCLUSION: After the theoretical class (including demonstration), only one of the 30-items checklist for skills achieved an index >= 90% of correct answers. On the other hand, an index of correct answers greater than 90% was achieved in 26 (86.7%) of the 30 items after a practical training simulation, evidencing the importance of this training in the defibrillation procedure. PMID- 26353105 TI - [Managers' perspective on continuous health education in a region of Sao Paulo State]. AB - OBJECTIVE: Analysing the concepts of Continuous Health Education - CHE (EPS - in Portuguese), operated by municipal managers and translated into official documents. METHOD: Qualitative research with the use of official documents and semi-structured interviews with the Municipal Health Secretaries or Coordinators of Primary Health Care in the Northeast Region of Sao Paulo State, and thematic analysis of empirical material. RESULTS: Results indicate difficulties in the municipalities problematizing their management practices, services and health care; EPS tools presented are insufficient and unsatisfactory for amending the array of problems raised and are still far from the routine of Primary Care services. CONCLUSION: Despite efforts to implement EPS actions for the strengthening of primary care, the process appears to be incipient. PMID- 26353106 TI - [Skin tear prevalence and associated factors: a systematic review]. AB - OBJECTIVE: To identify and analyse skin tear prevalence and factors associated with its occurrence. METHOD: Systematic review of literature of studies published until June 2014 including studies published in full in English, Spanish or Portuguese. The studies were analysed according to the Strengthening the Reporting of Observational Studies in Epidemiology and the Guidelines for Critically Appraising Studies of Prevalence or Incidence of a Health Problem. RESULTS: The analysis of eight studies showed skin tear prevalence of 3.3% to 22% in the hospital setting and 5.5% to 19.5% in homecare. Advanced age, dependence on basic activities of daily life, frail elderly, level of mobility, agitated behavior, non-responsiveness, greater risk for concurrent development of pressure ulcers, cognitive impairment, spasticity and photoaging were cited as risk factors. CONCLUSION: Skin tear prevalence ranged from 3.3% to 22% and is mainly associated with advanced age and dependence on basic activities of daily life. PMID- 26353107 TI - [Disinfection with sodium hypochlorite in hospital environmental surfaces in the reduction of contamination and infection prevention: a systematic review]. AB - OBJECTIVE: To search for evidence of the efficiency of sodium hypochlorite on environmental surfaces in reducing contamination and prevention of healthcare associated infection HAIs. METHOD: Systematic review in accordance with the Cochrane Collaboration. RESULTS: We analyzed 14 studies, all controlled trials, published between 1989-2013. Most studies resulted in inhibition of microorganism growth. Some decreased infection, microorganism resistance and colonization, loss of efficiency in the presence of dirty and surface-dried viruses. CONCLUSION: The hypochlorite is an effective disinfectant, however, the issue of the direct relation with the reduction of HAIs remains. The absence of control for confounding variables in the analyzed studies made the meta-analysis performance inadequate. The evaluation of internal validity using CONSORT and TREND was not possible because its contents were not appropriate to laboratory and microbiological studies. As a result, there is an urgent need for developing specific protocol for evaluating such studies. PMID- 26353108 TI - [Offshore work and the work of nurses on board: an integrative review]. AB - OBJECTIVE: To know the production of theoretical approaches on issues related to offshore work and the work of offshore nurses. METHOD: Integrative literature review conducted in the databases of LILACS, BDENF, MEDLINE, SciELO and Index PSI. RESULTS: We selected 33 studies published in national and international journals between 1997 and 2014. The thematic analysis corpus resulted in four central themes: offshore work environment; amid work adversities, an escape; structuring of offshore health and safety services; in search of safe practices. CONCLUSION: This study contributes to the offshore work of nurses in relation to the nature of work, acting amid adversities and the restless search for safe practices in the open sea. PMID- 26353109 TI - Single-Cell Analysis and Next-Generation Immuno-Sequencing Show That Multiple Clones Persist in Patients with Chronic Lymphocytic Leukemia. AB - The immunoglobulin heavy chain (IGH) gene rearrangement in chronic lymphocytic leukemia (CLL) provides a unique molecular signature; however, we demonstrate that 26/198 CLL patients (13%) had more than one IGH rearrangement, indicating the power of molecular technology over phenotypic analysis. Single-cell PCR analysis and next-generation immuno-sequencing identified IGH-defined clones. In 23% (18/79) of cases whose clones carried unmutated immunoglobulin heavy chain variable (IGHV) genes (U-CLL), IGH rearrangements were bialleic with one productive (P) and one non-productive (NP) allele. Two U-CLL were biclonal, each clone being monoallelic (P). In 119 IGHV-mutated (M-CLL) cases, one had biallelic rearrangements in their CLL (P/NP) and five had 2-4 distinct clones. Allelic exclusion was maintained in all B-clones analyzed. Based on single-cell PCR analysis, 5/11 partner clones (45%) reached levels of >5x10(9) cells/L, suggesting second CLL clones. Partner clones persisted over years. Conventional IGH characterization and next-generation sequencing of 13 CLL, 3 multiple myeloma, 2 Waldenstrom's macroglobulinemia and 3 age-matched healthy donors consistently identified the same rearranged IGH sequences. Most multiple clones occurred in M-CLL, perhaps indicative of weak clonal dominance, thereby associating with a good prognosis. In contrast, biallelic CLL occurred primarily in U-CLL thus being associated with poor prognosis. Extending beyond intra-clonal diversity, molecular analysis of clonal evolution and apparent subclones in CLL may also reflect inter-clonal diversity. PMID- 26353110 TI - Child Mortality after Discharge from a Health Facility following Suspected Pneumonia, Meningitis or Septicaemia in Rural Gambia: A Cohort Study. AB - OBJECTIVE: To measure mortality and its risk factors among children discharged from a health centre in rural Gambia. METHODS: We conducted a cohort study between 12 May 2008 and 11 May 2012. Children aged 2-59 months, admitted with suspected pneumonia, sepsis, or meningitis after presenting to primary and secondary care facilities, were followed for 180 days after discharge. We developed models associating post-discharge mortality with clinical syndrome on admission and clinical risk factors. FINDINGS: One hundred and five of 3755 (2.8%) children died, 80% within 3 months of discharge. Among children aged 2-11 and 12-59 months, there were 30 and 29 deaths per 1000 children per 180 days respectively, compared to 11 and 5 respectively in the resident population. Children with suspected pneumonia unaccompanied by clinically severe malnutrition (CSM) had the lowest risk of post-discharge mortality. Mortality increased in children with suspected meningitis or septicaemia without CSM (hazard ratio [HR] 2.6 and 2.2 respectively). The risk of mortality greatly increased with CSM on admission: CSM with suspected pneumonia (HR 8.1; 95% confidence interval (CI) 4.4 to 15), suspected sepsis (HR 18.4; 95% CI 11.3 to 30), or suspected meningitis (HR 13.7; 95% CI 4.2 to 45). Independent associations with mortality were: mid upper arm circumference (MUAC) of 11.5-13.0 cm compared to >13.0 cm (HR 7.2; 95% CI 3.0 to 17.0), MUAC 10.5-11.4 cm (HR 24; 95% CI 9.4 to 62), and MUAC <10.5 cm (HR 44; 95% CI 18 to 108), neck stiffness (HR 10.4; 95% CI 3.1 to 34.8), non medical discharge (HR 4.7; 95% CI 2.0 to 10.9), dry season discharge (HR 2.0; 95% CI 1.2 to 3.3), while greater haemoglobin (HR 0.82; 0.73 to 0.91), axillary temperature (HR 0.71; 95% CI 0.58 to 0.87), and oxygen saturation (HR 0.96; 95% CI 0.93 to 0.99) were associated with reduced mortality. CONCLUSION: Gambian children experience increased mortality after discharge from primary and secondary care. Interventions should target both moderately and severely malnourished children. PMID- 26353111 TI - The Oldest, Slowest Rainforests in the World? Massive Biomass and Slow Carbon Dynamics of Fitzroya cupressoides Temperate Forests in Southern Chile. AB - Old-growth temperate rainforests are, per unit area, the largest and most long lived stores of carbon in the terrestrial biosphere, but their carbon dynamics have rarely been described. The endangered Fitzroya cupressoides forests of southern South America include stands that are probably the oldest dense forest stands in the world, with long-lived trees and high standing biomass. We assess and compare aboveground biomass, and provide the first estimates of net primary productivity (NPP), carbon allocation and mean wood residence time in medium-age stands in the Alerce Costero National Park (AC) in the Coastal Range and in old growth forests in the Alerce Andino National Park (AA) in the Andean Cordillera. Aboveground live biomass was 113-114 Mg C ha(-1) and 448-517 Mg C ha(-1) in AC and AA, respectively. Aboveground productivity was 3.35-3.36 Mg C ha(-1) year(-1) in AC and 2.22-2.54 Mg C ha(-1) year(-1) in AA, values generally lower than others reported for temperate wet forests worldwide, mainly due to the low woody growth of Fitzroya. NPP was 4.21-4.24 and 3.78-4.10 Mg C ha(-1) year(-1) in AC and AA, respectively. Estimated mean wood residence time was a minimum of 539-640 years for the whole forest in the Andes and 1368-1393 years for only Fitzroya in this site. Our biomass estimates for the Andes place these ecosystems among the most massive forests in the world. Differences in biomass production between sites seem mostly apparent as differences in allocation rather than productivity. Residence time estimates for Fitzroya are the highest reported for any species and carbon dynamics in these forests are the slowest reported for wet forests worldwide. Although primary productivity is low in Fitzroya forests, they probably act as ongoing biomass carbon sinks on long-term timescales due to their low mortality rates and exceptionally long residence times that allow biomass to be accumulated for millennia. PMID- 26353112 TI - Canine Platelet Lysate Is Inferior to Fetal Bovine Serum for the Isolation and Propagation of Canine Adipose Tissue- and Bone Marrow-Derived Mesenchymal Stromal Cells. AB - BACKGROUND: Mesenchymal stromal cells (MSC) are increasingly investigated for their clinical utility in dogs. Fetal bovine serum (FBS) is a common culture supplement used for canine MSC expansion. However, FBS content is variable, its clinical use carries risk of an immune response, and its cost is increasing due to global demand. Platelet lysate (PL) has proven to be a suitable alternative to FBS for expansion of human MSC. HYPOTHESIS AND OBJECTIVES: We hypothesized that canine adipose tissue (AT) and bone marrow (BM) MSC could be isolated and expanded equally in PL and FBS at conventionally-used concentrations with differentiation of these MSC unaffected by choice of supplement. Our objectives were to evaluate the use of canine PL in comparison with FBS at four stages: 1) isolation, 2) proliferation, 3) spontaneous differentiation, and 4) directed differentiation. RESULTS: 1) Medium with 10% PL was unable to isolate MSC. 2) MSC, initially isolated in FBS-supplemented media, followed a dose-dependent response with no significant difference between PL and FBS cultures at up to 20% (AT) or 30% (BM) enrichment. Beyond these respective peaks, proliferation fell in PL cultures only, while a continued dose-dependent proliferation response was noted in FBS cultures. 3) Further investigation indicated PL expansion culture was inducing spontaneous adipogenesis in concentrations as low as 10% and as early as 4 days in culture. 4) MSC isolated in FBS, but expanded in either FBS or PL, maintained ability to undergo directed adipogenesis and osteogenesis, but not chondrogenesis. CONCLUSIONS/SIGNIFICANCE: Canine PL did not support establishment of MSC colonies from AT and BM, nor expansion of MSC, which appear to undergo spontaneous adipogenesis in response to PL exposure. In vivo studies are warranted to determine if concurrent use of MSC with any platelet-derived products such as platelet-rich plasma are associated with synergistic, neutral or antagonistic effects. PMID- 26353113 TI - Bayesian adaptive dose-escalation procedures for binary and continuous responses utilizing a gain function. AB - One of the main aims of early phase clinical trials is to identify a safe dose with an indication of therapeutic benefit to administer to subjects in further studies. Ideally therefore, dose-limiting events (DLEs) and responses indicative of efficacy should be considered in the dose-escalation procedure. Several methods have been suggested for incorporating both DLEs and efficacy responses in early phase dose-escalation trials. In this paper, we describe and evaluate a Bayesian adaptive approach based on one binary response (occurrence of a DLE) and one continuous response (a measure of potential efficacy) per subject. A logistic regression and a linear log-log relationship are used respectively to model the binary DLEs and the continuous efficacy responses. A gain function concerning both the DLEs and efficacy responses is used to determine the dose to administer to the next cohort of subjects. Stopping rules are proposed to enable efficient decision making. Simulation results shows that our approach performs better than taking account of DLE responses alone. To assess the robustness of the approach, scenarios where the efficacy responses of subjects are generated from an Emax model, but modelled by the linear log-log model are also considered. This evaluation shows that the simpler log-log model leads to robust recommendations even under this model showing that it is a useful approximation to the difficulty in estimating Emax model. Additionally, we find comparable performance to alternative approaches using efficacy and safety for dose-finding. PMID- 26353114 TI - Using the Electronic Nose to Identify Airway Infection during COPD Exacerbations. AB - BACKGROUND: The electronic nose (e-nose) detects volatile organic compounds (VOCs) in exhaled air. We hypothesized that the exhaled VOCs print is different in stable vs. exacerbated patients with chronic obstructive pulmonary disease (COPD), particularly if the latter is associated with airway bacterial infection, and that the e-nose can distinguish them. METHODS: Smell-prints of the bacteria most commonly involved in exacerbations of COPD (ECOPD) were identified in vitro. Subsequently, we tested our hypothesis in 93 patients with ECOPD, 19 of them with pneumonia, 50 with stable COPD and 30 healthy controls in a cross-sectional case controlled study. Secondly, ECOPD patients were re-studied after 2 months if clinically stable. Exhaled air was collected within a Tedlar bag and processed by a Cynarose 320 e-nose. Breath-prints were analyzed by Linear Discriminant Analysis (LDA) with "One Out" technique and Sensor logic Relations (SLR). Sputum samples were collected for culture. RESULTS: ECOPD with evidence of infection were significantly distinguishable from non-infected ECOPD (p = 0.018), with better accuracy when ECOPD was associated to pneumonia. The same patients with ECOPD were significantly distinguishable from stable COPD during follow-up (p = 0.018), unless the patient was colonized. Additionally, breath-prints from COPD patients were significantly distinguished from healthy controls. Various bacteria species were identified in culture but the e-nose was unable to identify accurately the bacteria smell-print in infected patients. CONCLUSION: E-nose can identify ECOPD, especially if associated with airway bacterial infection or pneumonia. PMID- 26353116 TI - Kapp SJ, Larsson I, Van De Weert M, Cardenas M, Jorgensen L. 2015. Competitive Adsorption of Monoclonal Antibodies and Nonionic Surfactants at Solid Hydrophobic Surfaces. 2015. J Pharm Sci 104:593-601. PMID- 26353115 TI - Constitutive STAT3 Phosphorylation in Circulating CD4+ T Lymphocytes Associates with Disease Activity and Treatment Response in Recent-Onset Rheumatoid Arthritis. AB - The aim of the present study was to examine constitutive signal transducer and activator of transcription 3 (STAT3) phosphorylation in circulating leukocytes as a candidate biomarker in rheumatoid arthritis (RA). 25 patients with recent onset, untreated RA provided samples for whole blood flow cytometric determination of intracellular STAT3 phosphorylation, expressed as relative fluorescence units. The occurrence of constitutive STAT3 phosphorylation was evaluated by determining proportion of STAT3-phosphorylated cells among different leukocyte subtypes. Plasma levels of interleukin (IL)-6, IL-17 and IL-21 were measured by immunoassay, radiographs of hands and feet were examined and disease activity score (DAS28) was determined. Biomarkers were restudied and treatment response (according to European League Against Rheumatism) was determined after 12 months of treatment with disease-modifying antirheumatic drugs. At baseline, constitutive phosphorylation of STAT3 occurred in CD4+ T cells of 14 (56%) patients, CD8+ T cells of 13 (52%) patients, in CD19+ B cells of 7 (28%) patients, and in CD14+ monocytes of 12 (48%) patients. STAT3 phosphorylation levels of CD4+ T cells associated with DAS28, and those of all leukocyte subtypes studied associated with erosive disease. The presence of constitutive STAT3 phosphorylation in CD4+ T lymphocytes, pSTAT3 fluorescence intensity of CD4+ and CD8+ T cells and C-reactive protein (CRP) levels at baseline associated with good treatment response. In conclusion, constitutive STAT3 phosphorylation in circulating CD4+ T cells is common in recent-onset untreated RA and associates with good treatment response in patients characterized by high disease activity and the presence of systemic inflammation. PMID- 26353117 TI - Diagnostic Accuracy of Urine Protein/Creatinine Ratio Is Influenced by Urine Concentration. AB - BACKGROUND: The usage of urine protein/creatinine ratio to estimate daily urine protein excretion is prevalent, but relatively little attention has been paid to the influence of urine concentration and its impact on test accuracy. We took advantage of 24-hour urine collection to examine both urine protein/creatinine ratio (UPCR) and daily urine protein excretion, with the latter as the reference standard. Specific gravity from a concomitant urinalysis of the same urine sample was used to indicate the urine concentration. METHODS: During 2010 to 2014, there were 540 adequately collected 24h urine samples with protein concentration, creatinine concentration, total volume, and a concomitant urinalysis of the same sample. Variables associated with an accurate UPCR estimation were determined by multivariate linear regression analysis. Receiver operating characteristic (ROC) curves were generated to determine the discriminant cut-off values of urine creatinine concentration for predicting an accurate UPCR estimation in either dilute or concentrated urine samples. RESULTS: Our findings indicated that for dilute urine, as indicated by a low urine specific gravity, UPCR is more likely to overestimate the actual daily urine protein excretion. On the contrary, UPCR of concentrated urine is more likely to result in an underestimation. By ROC curve analysis, the best cut-off value of urine creatinine concentration for predicting overestimation by UPCR of dilute urine (specific gravity ? 1.005) was ? 38.8 mg/dL, whereas the best cut-off values of urine creatinine for predicting underestimation by UPCR of thick urine were ? 63.6 mg/dL (specific gravity ? 1.015), ? 62.1 mg/dL (specific gravity ? 1.020), ? 61.5 mg/dL (specific gravity ? 1.025), respectively. We also compared distribution patterns of urine creatinine concentration of 24h urine cohort with a concurrent spot urine cohort and found that the underestimation might be more profound in single voided samples. CONCLUSIONS: The UPCR in samples with low or high specific gravity is more likely to overestimate or underestimate actual daily urine protein amount, respectively, especially in a dilute urine sample with its creatinine below 38.8 mg/dL or a concentrated sample with its creatinine above 61.5 mg/dL. In particular, UPCR results should be interpreted with caution in cases that involve dilute urine samples because its overestimation may lead to an erroneous diagnosis of proteinuric renal disease or an incorrect staging of chronic kidney disease. PMID- 26353118 TI - Distress Calls of a Fast-Flying Bat (Molossus molossus) Provoke Inspection Flights but Not Cooperative Mobbing. AB - Many birds and mammals produce distress calls when captured. Bats often approach speakers playing conspecific distress calls, which has led to the hypothesis that bat distress calls promote cooperative mobbing. An alternative explanation is that approaching bats are selfishly assessing predation risk. Previous playback studies on bat distress calls involved species with highly maneuverable flight, capable of making close passes and tight circles around speakers, which can look like mobbing. We broadcast distress calls recorded from the velvety free-tailed bat, Molossus molossus, a fast-flying aerial-hawker with relatively poor maneuverability. Based on their flight behavior, we predicted that, in response to distress call playbacks, M. molossus would make individual passing inspection flights but would not approach in groups or approach within a meter of the distress call source. By recording responses via ultrasonic recording and infrared video, we found that M. molossus, and to a lesser extent Saccopteryx bilineata, made more flight passes during distress call playbacks compared to noise. However, only the more maneuverable S. bilineata made close approaches to the speaker, and we found no evidence of mobbing in groups. Instead, our findings are consistent with the hypothesis that single bats approached distress calls simply to investigate the situation. These results suggest that approaches by bats to distress calls should not suffice as clear evidence for mobbing. PMID- 26353120 TI - Trimodality Treatment of Malignant Pleural Mesothelioma: An Institutional Review. AB - OBJECTIVE: Malignant pleural mesothelioma (MPM) is a deadly disease with varying treatment options. This study retrospectively describes treatment practices at the University of Washington Medical System from 1980 to 2011, and evaluates the impact of trimodality therapy and radiation (photon and neutron) on survival. METHODS: A retrospective study was conducted on patients treated for MPM. Univariate and multivariate methods were utilized to evaluate potential factors associated with survival. Treatments received and baseline characteristics were included. Survival analysis of trimodality therapy was performed using a propensity score method to control for baseline characteristics. RESULTS: Among 78 eligible patients, the median age at diagnosis was 59 years and the median survival was 13.7 months. On multivariate analysis, the significant predictors of improved survival were age, smoking history, location, and receipt of radiation therapy or chemotherapy. In the 48 patients receiving radiation therapy, the difference in survival between neutron therapy and non-neutron therapy patients was not statistically significant: hazard ratio, 1.20 (95% confidence interval, 0.68-2.13), P=0.52. Patients receiving trimodality therapy were more likely to have early-stage disease (60% vs. 30%) and epithelioid histology (86% vs. 58%). In a propensity score-weighted Cox proportional hazards model, trimodality therapy patients had improved overall survival, hazard ratio 0.45, P=0.004, median 14.6 versus 8.6 months. CONCLUSIONS: Trimodality therapy was significantly associated with prolonged survival in patients with MPM, even when adjusting for baseline patient factors. Radiation therapy was associated with improved survival, but the modality of radiation therapy used was not associated with outcome. PMID- 26353119 TI - The Map in Our Head Is Not Oriented North: Evidence from a Real-World Environment. AB - Like most physical maps, recent research has suggested that cognitive maps of familiar environments may have a north-up orientation. We demonstrate that north orientation is not a necessary feature of cognitive maps and instead may arise due to coincidental alignment between cardinal directions and the built and natural environment. Experiment 1 demonstrated that pedestrians have difficulty pointing north while navigating a familiar real-world environment with roads, buildings, and green spaces oriented oblique to cardinal axes. Instead, north estimates tended to be parallel or perpendicular to roads. In Experiment 2, participants did not demonstrate privileged memory access when oriented toward north while making relative direction judgments. Instead, retrieval was fastest and most accurate when orientations were aligned with roads. In sum, cognitive maps are not always oriented north. Rather, in some real-world environments they can be oriented with respect to environment-specific features, serving as convenient reference systems for organizing and using spatial memory. PMID- 26353121 TI - Concurrent Radiotherapy With Cetuximab or Platinum-based Chemotherapy for Locally Advanced Cutaneous Squamous Cell Carcinoma of the Head and Neck. AB - OBJECTIVES: The management of high-risk cutaneous squamous cell carcinoma of the head and neck (SCCHN) is not well defined. We review outcomes in patients with locally advanced cutaneous SCCHN treated with radiation and concomitant platinum (Pt)-based chemotherapy or cetuximab (Cx). METHODS: We identified 23 patients treated at our institution from 2007 to 2014. Systemic therapy consisted of Pt based chemotherapy for 15 (65%) patients and Cx for 8 (35%) patients. Treatment intent was definitive for 48% and adjuvant for 52% of the cases. RESULTS: The majority (87%) of patients had stage III/IV disease and 9 (39%) patients had unresectable disease. All patients were being treated for recurrent disease. Aside from median age (59 Pt vs. 71 Cx, P=0.04), there were no significant differences in patient and tumor characteristics between those receiving Pt versus Cx therapy. At mean follow-up of 24 months, locoregional recurrence and distant failure were observed in 52% and 17% of all patients, respectively. Estimated 2-year disease-free survival and overall survival in the Cx versus Pt groups were: 50% versus 30% (P=0.25), and 73% versus 40% (P=0.32), respectively. CONCLUSIONS: Radiotherapy with either concurrent Pt or Cx appears to offer similar clinical outcomes in patients with locally advanced cutaneous SCCHN. PMID- 26353123 TI - A Unified Framework for Event Summarization and Rare Event Detection from Multiple Views. AB - A novel approach for event summarization and rare event detection is proposed. Unlike conventional methods that deal with event summarization and rare event detection independently, our method solves them in a single framework by transforming them into a graph editing problem. In our approach, a video is represented by a graph, each node of which indicates an event obtained by segmenting the video spatially and temporally. The edges between nodes describe the relationship between events. Based on the degree of relations, edges have different weights. After learning the graph structure, our method finds subgraphs that represent event summarization and rare events in the video by editing the graph, that is, merging its subgraphs or pruning its edges. The graph is edited to minimize a predefined energy model with the Markov Chain Monte Carlo (MCMC) method. The energy model consists of several parameters that represent the causality, frequency, and significance of events. We design a specific energy model that uses these parameters to satisfy each objective of event summarization and rare event detection. The proposed method is extended to obtain event summarization and rare event detection results across multiple videos captured from multiple views. For this purpose, the proposed method independently learns and edits each graph of individual videos for event summarization or rare event detection. Then, the method matches the extracted multiple graphs to each other, and constructs a single composite graph that represents event summarization or rare events from multiple views. Experimental results show that the proposed approach accurately summarizes multiple videos in a fully unsupervised manner. Moreover, the experiments demonstrate that the approach is advantageous in detecting rare transition of events. PMID- 26353122 TI - Culture in the Courtroom: Ethnocentrism and Juror Decision-Making. AB - The purpose of this study was to investigate whether a culturally-based argument in a non-insane automatism defense would be detrimental or beneficial to the defendant. We also examined how juror ethnocentrism might affect perceptions of such a defense. Participants read a fictional filicide homicide case in which the defendant claimed to have blacked out during the crime; we manipulated whether culture was used as an explanation for what precipitated the defendant's blackout. We conducted path analyses to assess the role of ethnocentrism in predicting lower defendant credibility, and harsher verdict decisions. Results revealed an interaction between ethnocentrism and defense type, such that ethnocentrism related to lower perceived defendant credibility in the cultural condition, but not in the standard automatism condition. This study marks a starting point for empirically investigating the role of culture in the courtroom, which may aid scholars in discussing the merits of a standalone cultural defense. PMID- 26353124 TI - Bayesian CP Factorization of Incomplete Tensors with Automatic Rank Determination. AB - CANDECOMP/PARAFAC (CP) tensor factorization of incomplete data is a powerful technique for tensor completion through explicitly capturing the multilinear latent factors. The existing CP algorithms require the tensor rank to be manually specified, however, the determination of tensor rank remains a challenging problem especially for CP rank . In addition, existing approaches do not take into account uncertainty information of latent factors, as well as missing entries. To address these issues, we formulate CP factorization using a hierarchical probabilistic model and employ a fully Bayesian treatment by incorporating a sparsity-inducing prior over multiple latent factors and the appropriate hyperpriors over all hyperparameters, resulting in automatic rank determination. To learn the model, we develop an efficient deterministic Bayesian inference algorithm, which scales linearly with data size. Our method is characterized as a tuning parameter-free approach, which can effectively infer underlying multilinear factors with a low-rank constraint, while also providing predictive distributions over missing entries. Extensive simulations on synthetic data illustrate the intrinsic capability of our method to recover the ground truth of CP rank and prevent the overfitting problem, even when a large amount of entries are missing. Moreover, the results from real-world applications, including image inpainting and facial image synthesis, demonstrate that our method outperforms state-of-the-art approaches for both tensor factorization and tensor completion in terms of predictive performance. PMID- 26353125 TI - Cross-Domain Matching with Squared-Loss Mutual Information. AB - The goal of cross-domain matching (CDM) is to find correspondences between two sets of objects in different domains in an unsupervised way. CDM has various interesting applications, including photo album summarization where photos are automatically aligned into a designed frame expressed in the Cartesian coordinate system, and temporal alignment which aligns sequences such as videos that are potentially expressed using different features. In this paper, we propose an information-theoretic CDM framework based on squared-loss mutual information (SMI). The proposed approach can directly handle non-linearly related objects/sequences with different dimensions, with the ability that hyper parameters can be objectively optimized by cross-validation. We apply the proposed method to several real-world problems including image matching, unpaired voice conversion, photo album summarization, cross-feature video and cross-domain video-to-mocap alignment, and Kinect-based action recognition, and experimentally demonstrate that the proposed method is a promising alternative to state-of-the art CDM methods. PMID- 26353126 TI - Distribution Matching with the Bhattacharyya Similarity: A Bound Optimization Framework. AB - We present efficient graph cut algorithms for three problems: (1) finding a region in an image, so that the histogram (or distribution) of an image feature within the region most closely matches a given model; (2) co-segmentation of image pairs and (3) interactive image segmentation with a user-provided bounding box. Each algorithm seeks the optimum of a global cost function based on the Bhattacharyya measure, a convenient alternative to other matching measures such as the Kullback-Leibler divergence. Our functionals are not directly amenable to graph cut optimization as they contain non-linear functions of fractional terms, which make the ensuing optimization problems challenging. We first derive a family of parametric bounds of the Bhattacharyya measure by introducing an auxiliary labeling. Then, we show that these bounds are auxiliary functions of the Bhattacharyya measure, a result which allows us to solve each problem efficiently via graph cuts. We show that the proposed optimization procedures converge within very few graph cut iterations. Comprehensive and various experiments, including quantitative and comparative evaluations over two databases, demonstrate the advantages of the proposed algorithms over related works in regard to optimality, computational load, accuracy and flexibility. PMID- 26353127 TI - Efficient Learning of Image Super-Resolution and Compression Artifact Removal with Semi-Local Gaussian Processes. AB - Improving the quality of degraded images is a key problem in image processing, but the breadth of the problem leads to domain-specific approaches for tasks such as super-resolution and compression artifact removal. Recent approaches have shown that a general approach is possible by learning application-specific models from examples; however, learning models sophisticated enough to generate high quality images is computationally expensive, and so specific per-application or per-dataset models are impractical. To solve this problem, we present an efficient semi-local approximation scheme to large-scale Gaussian processes. This allows efficient learning of task-specific image enhancements from example images without reducing quality. As such, our algorithm can be easily customized to specific applications and datasets, and we show the efficiency and effectiveness of our approach across five domains: single-image super-resolution for scene, human face, and text images, and artifact removal in JPEG- and JPEG 2000-encoded images. PMID- 26353128 TI - Fused Lasso Screening Rules via the Monotonicity of Subdifferentials. AB - Fused Lasso is a popular regression technique that encodes the smoothness of the data. It has been applied successfully to many applications with a smooth feature structure. However, the computational cost of the existing solvers for fused Lasso is prohibitive when the feature dimension is extremely large. In this paper, we propose novel screening rules that are able to quickly identity the adjacent features with the same coefficients. As a result, the number of variables to be estimated can be significantly reduced, leading to substantial savings in computational cost and memory usage. To the best of our knowledge, the proposed approach is the first attempt to develop screening methods for the fused Lasso problem with general data matrix. Our major contributions are: 1) we derive a new dual formulation of fused Lasso that comes with several desirable properties; 2) we show that the new dual formulation of fused Lasso is equivalent to that of the standard Lasso by two affine transformations; 3) we propose a novel framework for developing effective and efficient screening rules for fused Lasso via the monotonicity of the subdifferentials (FLAMS). Some appealing features of FLAMS are: 1) our methods are safe in the sense that the detected adjacent features are guaranteed to have the same coefficients; 2) the dataset needs to be scanned only once to run the screening, whose computational cost is negligible compared to that of solving the fused Lasso; (3) FLAMS is independent of the solvers and can be integrated with any existing solvers. We have evaluated the proposed FLAMS rules on both synthetic and real datasets. The experiments indicate that FLAMS is very effective in identifying the adjacent features with the same coefficients. The speedup gained by FLAMS can be orders of magnitude. PMID- 26353129 TI - Learning Efficient Sparse and Low Rank Models. AB - Parsimony, including sparsity and low rank, has been shown to successfully model data in numerous machine learning and signal processing tasks. Traditionally, such modeling approaches rely on an iterative algorithm that minimizes an objective function with parsimony-promoting terms. The inherently sequential structure and data-dependent complexity and latency of iterative optimization constitute a major limitation in many applications requiring real-time performance or involving large-scale data. Another limitation encountered by these modeling techniques is the difficulty of their inclusion in discriminative learning scenarios. In this work, we propose to move the emphasis from the model to the pursuit algorithm, and develop a process-centric view of parsimonious modeling, in which a learned deterministic fixed-complexity pursuit process is used in lieu of iterative optimization. We show a principled way to construct learnable pursuit process architectures for structured sparse and robust low rank models, derived from the iteration of proximal descent algorithms. These architectures learn to approximate the exact parsimonious representation at a fraction of the complexity of the standard optimization methods. We also show that appropriate training regimes allow to naturally extend parsimonious models to discriminative settings. State-of-the-art results are demonstrated on several challenging problems in image and audio processing with several orders of magnitude speed-up compared to the exact optimization algorithms. PMID- 26353130 TI - Object Tracking Benchmark. AB - Object tracking has been one of the most important and active research areas in the field of computer vision. A large number of tracking algorithms have been proposed in recent years with demonstrated success. However, the set of sequences used for evaluation is often not sufficient or is sometimes biased for certain types of algorithms. Many datasets do not have common ground-truth object positions or extents, and this makes comparisons among the reported quantitative results difficult. In addition, the initial conditions or parameters of the evaluated tracking algorithms are not the same, and thus, the quantitative results reported in literature are incomparable or sometimes contradictory. To address these issues, we carry out an extensive evaluation of the state-of-the art online object-tracking algorithms with various evaluation criteria to understand how these methods perform within the same framework. In this work, we first construct a large dataset with ground-truth object positions and extents for tracking and introduce the sequence attributes for the performance analysis. Second, we integrate most of the publicly available trackers into one code library with uniform input and output formats to facilitate large-scale performance evaluation. Third, we extensively evaluate the performance of 31 algorithms on 100 sequences with different initialization settings. By analyzing the quantitative results, we identify effective approaches for robust tracking and provide potential future research directions in this field. PMID- 26353131 TI - Recognising Planes in a Single Image. AB - We present a novel method to recognise planar structures in a single image and estimate their 3D orientation. This is done by exploiting the relationship between image appearance and 3D structure, using machine learning methods with supervised training data. As such, the method does not require specific features or use geometric cues, such as vanishing points. We employ general feature representations based on spatiograms of gradients and colour, coupled with relevance vector machines for classification and regression. We first show that using hand-labelled training data, we are able to classify pre-segmented regions as being planar or not, and estimate their 3D orientation. We then incorporate the method into a segmentation algorithm to detect multiple planar structures from a previously unseen image. PMID- 26353132 TI - Robust and Accurate Shape Model Matching Using Random Forest Regression-Voting. AB - A widely used approach for locating points on deformable objects in images is to generate feature response images for each point, and then to fit a shape model to these response images. We demonstrate that Random Forest regression-voting can be used to generate high quality response images quickly. Rather than using a generative or a discriminative model to evaluate each pixel, a regressor is used to cast votes for the optimal position of each point. We show that this leads to fast and accurate shape model matching when applied in the Constrained Local Model framework. We evaluate the technique in detail, and compare it with a range of commonly used alternatives across application areas: the annotation of the joints of the hands in radiographs and the detection of feature points in facial images. We show that our approach outperforms alternative techniques, achieving what we believe to be the most accurate results yet published for hand joint annotation and state-of-the-art performance for facial feature point detection. PMID- 26353133 TI - Single-Pedestrian Detection Aided by Two-Pedestrian Detection. AB - In this paper, we address the challenging problem of detecting pedestrians who appear in groups. A new approach is proposed for single-pedestrian detection aided by two-pedestrian detection. A mixture model of two-pedestrian detectors is designed to capture the unique visual cues which are formed by nearby pedestrians but cannot be captured by single-pedestrian detectors. A probabilistic framework is proposed to model the relationship between the configurations estimated by single- and two-pedestrian detectors, and to refine the single-pedestrian detection result using two-pedestrian detection. The two-pedestrian detector can integrate with any single-pedestrian detector. Twenty-five state-of-the-art single-pedestrian detection approaches are combined with the two-pedestrian detector on three widely used public datasets: Caltech, TUD-Brussels, and ETH. Experimental results show that our framework improves all these approaches. The average improvement is 9 percent on the Caltech-Test dataset, 11 percent on the TUD-Brussels dataset and 17 percent on the ETH dataset in terms of average miss rate. The lowest average miss rate is reduced from 37 to percent on the Caltech Test dataset, from 55 to 50 percent on the TUD-Brussels dataset and from 43 to 38 percent on the ETH dataset. PMID- 26353134 TI - Sparse Multi-View Consistency for Object Segmentation. AB - Multiple view segmentation consists in segmenting objects simultaneously in several views. A key issue in that respect and compared to monocular settings is to ensure propagation of segmentation information between views while minimizing complexity and computational cost. In this work, we first investigate the idea that examining measurements at the projections of a sparse set of 3D points is sufficient to achieve this goal. The proposed algorithm softly assigns each of these 3D samples to the scene background if it projects on the background region in at least one view, or to the foreground if it projects on foreground region in all views. Second, we show how other modalities such as depth may be seamlessly integrated in the model and benefit the segmentation. The paper exposes a detailed set of experiments used to validate the algorithm, showing results comparable with the state of art, with reduced computational complexity. We also discuss the use of different modalities for specific situations, such as dealing with a low number of viewpoints or a scene with color ambiguities between foreground and background. PMID- 26353135 TI - Spatial Pyramid Pooling in Deep Convolutional Networks for Visual Recognition. AB - Existing deep convolutional neural networks (CNNs) require a fixed-size (e.g., 224 * 224) input image. This requirement is "artificial" and may reduce the recognition accuracy for the images or sub-images of an arbitrary size/scale. In this work, we equip the networks with another pooling strategy, "spatial pyramid pooling", to eliminate the above requirement. The new network structure, called SPP-net, can generate a fixed-length representation regardless of image size/scale. Pyramid pooling is also robust to object deformations. With these advantages, SPP-net should in general improve all CNN-based image classification methods. On the ImageNet 2012 dataset, we demonstrate that SPP-net boosts the accuracy of a variety of CNN architectures despite their different designs. On the Pascal VOC 2007 and Caltech101 datasets, SPP-net achieves state-of-the-art classification results using a single full-image representation and no fine tuning. The power of SPP-net is also significant in object detection. Using SPP net, we compute the feature maps from the entire image only once, and then pool features in arbitrary regions (sub-images) to generate fixed-length representations for training the detectors. This method avoids repeatedly computing the convolutional features. In processing test images, our method is 24 102 * faster than the R-CNN method, while achieving better or comparable accuracy on Pascal VOC 2007. In ImageNet Large Scale Visual Recognition Challenge (ILSVRC) 2014, our methods rank #2 in object detection and #3 in image classification among all 38 teams. This manuscript also introduces the improvement made for this competition. PMID- 26353136 TI - Variational Infinite Hidden Conditional Random Fields. AB - Hidden conditional random fields (HCRFs) are discriminative latent variable models which have been shown to successfully learn the hidden structure of a given classification problem. An Infinite hidden conditional random field is a hidden conditional random field with a countably infinite number of hidden states, which rids us not only of the necessity to specify a priori a fixed number of hidden states available but also of the problem of overfitting. Markov chain Monte Carlo (MCMC) sampling algorithms are often employed for inference in such models. However, convergence of such algorithms is rather difficult to verify, and as the complexity of the task at hand increases the computational cost of such algorithms often becomes prohibitive. These limitations can be overcome by variational techniques. In this paper, we present a generalized framework for infinite HCRF models, and a novel variational inference approach on a model based on coupled Dirichlet Process Mixtures, the HCRF-DPM. We show that the variational HCRF-DPM is able to converge to a correct number of represented hidden states, and performs as well as the best parametric HCRFs-chosen via cross validation-for the difficult tasks of recognizing instances of agreement, disagreement, and pain in audiovisual sequences. PMID- 26353137 TI - Multi-Orientation Scene Text Detection with Adaptive Clustering. AB - Text detection in natural scene images is an important prerequisite for many content-based image analysis tasks, while most current research efforts only focus on horizontal or near horizontal scene text. In this paper, first we present a unified distance metric learning framework for adaptive hierarchical clustering, which can simultaneously learn similarity weights (to adaptively combine different feature similarities) and the clustering threshold (to automatically determine the number of clusters). Then, we propose an effective multi-orientation scene text detection system, which constructs text candidates by grouping characters based on this adaptive clustering. Our text candidates construction method consists of several sequential coarse-to-fine grouping steps: morphology-based grouping via single-link clustering, orientation-based grouping via divisive hierarchical clustering, and projection-based grouping also via divisive clustering. The effectiveness of our proposed system is evaluated on several public scene text databases, e.g., ICDAR Robust Reading Competition data sets (2011 and 2013), MSRA-TD500 and NEOCR. Specifically, on the multi orientation text data set MSRA-TD500, the f measure of our system is 71 percent, much better than the state-of-the-art performance. We also construct and release a practical challenging multi-orientation scene text data set (USTB-SV1K), which is available at http://prir.ustb.edu.cn/TexStar/MOMV-text-detection/. PMID- 26353138 TI - Semi-Continuity of Skeletons in Two-Manifold and Discrete Voronoi Approximation. AB - The skeleton of a 2D shape is an important geometric structure in pattern analysis and computer vision. In this paper we study the skeleton of a 2D shape in a two-manifold M , based on a geodesic metric. We present a formal definition of the skeleton S(Omega) for a shape Omega in M and show several properties that make S(Omega) distinct from its Euclidean counterpart in R(2). We further prove that for a shape sequence {Omegai} that converge to a shape Omega in M, the mapping Omega-> S(Omega) is lower semi-continuous. A direct application of this result is that we can use a set P of sample points to approximate the boundary of a 2D shape Omega, and the Voronoi diagram of P inside Omega ? M gives a good approximation to the skeleton S(Omega) . Examples of skeleton computation in topography and brain morphometry are illustrated. PMID- 26353139 TI - Action Spotting and Recognition Based on a Spatiotemporal Orientation Analysis. AB - This paper provides a unified framework for the interrelated topics of action spotting, the spatiotemporal detection and localization of human actions in video, and action recognition, the classification of a given video into one of several predefined categories. A novel compact local descriptor of video dynamics in the context of action spotting and recognition is introduced based on visual spacetime oriented energy measurements. This descriptor is efficiently computed directly from raw image intensity data and thereby forgoes the problems typically associated with flow-based features. Importantly, the descriptor allows for the comparison of the underlying dynamics of two spacetime video segments irrespective of spatial appearance, such as differences induced by clothing, and with robustness to clutter. An associated similarity measure is introduced that admits efficient exhaustive search for an action template, derived from a single exemplar video, across candidate video sequences. The general approach presented for action spotting and recognition is amenable to efficient implementation, which is deemed critical for many important applications. For action spotting, details of a real-time GPU-based instantiation of the proposed approach are provided. Empirical evaluation of both action spotting and action recognition on challenging datasets suggests the efficacy of the proposed approach, with state of-the-art performance documented on standard datasets. PMID- 26353140 TI - Hop-Diffusion Monte Carlo for Epipolar Geometry Estimation between Very Wide Baseline Images. AB - We present a Monte Carlo approach for epipolar geometry estimation that efficiently searches for minimal sets of inlier correspondences in the presence of many outliers in the putative correspondence set, a condition that is prevalent when we have wide baselines, significant scale changes, rotations in depth, occlusion, and repeated patterns. The proposed Monte Carlo algorithm uses Balanced LOcal and Global Search (BLOGS) to find the best minimal set of correspondences. The local search is a diffusion process using Joint Feature Distributions that captures the dependencies among the correspondences. And, the global search is a hopping search process across the minimal set space controlled by photometric properties. Using a novel experimental protocol that involves computing errors for manually marked ground truth points and images with outlier rates as high as 90 percent, we find that BLOGS is better than related approaches such as MAPSAC, NAPSAC, and BEEM. BLOGS results are of similar quality as other approaches, but BLOGS generate them in 10 times fewer iterations. The time per iteration for BLOGS is also the lowest among the ones we studied. PMID- 26353141 TI - Shape Representation and Registration in Vector Implicit Spaces: Adopting a Closed-Form Solution in the Optimization Process. AB - In this paper, a novel method to solve the shape registration problem covering both global and local deformations is proposed. The vector distance function (VDF) is used to represent source and target shapes. The problem is formulated as an energy optimization process by matching the VDFs of the source and target shapes. The minimization process results in estimating the transformation parameters for the global and local deformation cases. Gradient descent optimization handles the computation of scaling, rotation, and translation matrices used to minimize the global differences between source and target shapes. Nonrigid deformations require a large number of parameters which make the use of the gradient descent minimization a very time-consuming process. We propose to compute the local deformation parameters using a closed-form solution as a linear system of equations derived from approximating an objective function. Extensive experimental validations and comparisons performed on generalized 2D shape data demonstrate the robustness and effectiveness of the method. PMID- 26353142 TI - Asymptotic Generalization Bound of Fisher's Linear Discriminant Analysis. AB - Fisher's linear discriminant analysis (FLDA) is an important dimension reduction method in statistical pattern recognition. It has been shown that FLDA is asymptotically Bayes optimal under the homoscedastic Gaussian assumption. However, this classical result has the following two major limitations: 1) it holds only for a fixed dimensionality D, and thus does not apply when D and the training sample size N are proportionally large; 2) it does not provide a quantitative description on how the generalization ability of FLDA is affected by D and N. In this paper, we present an asymptotic generalization analysis of FLDA based on random matrix theory, in a setting where both D and N increase and D/N > gamma ? [0,1). The obtained lower bound of the generalization discrimination power overcomes both limitations of the classical result, i.e., it is applicable when D and N are proportionally large and provides a quantitative description of the generalization ability of FLDA in terms of the ratio gamma = D/N and the population discrimination power. Besides, the discrimination power bound also leads to an upper bound on the generalization error of binary-classification with FLDA. PMID- 26353144 TI - Discriminative Non-Linear Stationary Subspace Analysis for Video Classification. AB - Low-dimensional representations are key to the success of many video classification algorithms. However, the commonly-used dimensionality reduction techniques fail to account for the fact that only part of the signal is shared across all the videos in one class. As a consequence, the resulting representations contain instance-specific information, which introduces noise in the classification process. In this paper, we introduce non-linear stationary subspace analysis: a method that overcomes this issue by explicitly separating the stationary parts of the video signal (i.e., the parts shared across all videos in one class), from its non-stationary parts (i.e., the parts specific to individual videos). Our method also encourages the new representation to be discriminative, thus accounting for the underlying classification problem. We demonstrate the effectiveness of our approach on dynamic texture recognition, scene classification and action recognition. PMID- 26353143 TI - Bin Ratio-Based Histogram Distances and Their Application to Image Classification. AB - Large variations in image background may cause partial matching and normalization problems for histogram-based representations, i.e., the histograms of the same category may have bins which are significantly different, and normalization may produce large changes in the differences between corresponding bins. In this paper, we deal with this problem by using the ratios between bin values of histograms, rather than bin values' differences which are used in the traditional histogram distances. We propose a bin ratio-based histogram distance (BRD), which is an intra-cross-bin distance, in contrast with previous bin-to-bin distances and cross-bin distances. The BRD is robust to partial matching and histogram normalization, and captures correlations between bins with only a linear computational complexity. We combine the BRD with the l1 histogram distance and the chi(2) histogram distance to generate the l1 BRD and the chi(2) BRD, respectively. These combinations exploit and benefit from the robustness of the BRD under partial matching and the robustness of the l1 and chi(2) distances to small noise. We propose a method for assessing the robustness of histogram distances to partial matching. The BRDs and logistic regression-based histogram fusion are applied to image classification. The experimental results on synthetic data sets show the robustness of the BRDs to partial matching, and the experiments on seven benchmark data sets demonstrate promising results of the BRDs for image classification. PMID- 26353145 TI - Domain Adaptation of Deformable Part-Based Models. AB - The accuracy of object classifiers can significantly drop when the training data (source domain) and the application scenario (target domain) have inherent differences. Therefore, adapting the classifiers to the scenario in which they must operate is of paramount importance. We present novel domain adaptation (DA) methods for object detection. As proof of concept, we focus on adapting the state of-the-art deformable part-based model (DPM) for pedestrian detection. We introduce an adaptive structural SVM (A-SSVM) that adapts a pre-learned classifier between different domains. By taking into account the inherent structure in feature space (e.g., the parts in a DPM), we propose a structure aware A-SSVM (SA-SSVM). Neither A-SSVM nor SA-SSVM needs to revisit the source domain training data to perform the adaptation. Rather, a low number of target domain training examples (e.g., pedestrians) are used. To address the scenario where there are no target-domain annotated samples, we propose a self-adaptive DPM based on a self-paced learning (SPL) strategy and a Gaussian Process Regression (GPR). Two types of adaptation tasks are assessed: from both synthetic pedestrians and general persons (PASCAL VOC) to pedestrians imaged from an on board camera. Results show that our proposals avoid accuracy drops as high as 15 points when comparing adapted and non-adapted detectors. PMID- 26353146 TI - Epipolar Geometry Estimation for Urban Scenes with Repetitive Structures. AB - Algorithms for the estimation of epipolar geometry from a pair of images have been very successful in dealing with challenging wide baseline images. In this paper the problem of scenes with repeated structures is addressed, dealing with the common case where the overlap between the images consists mainly of facades of a building. These facades may contain many repeated structures that can not be matched locally, causing state-of-the-art algorithms to fail. Assuming that the repeated structures lie on a planar surface in an ordered fashion the goal is to match them. Our algorithm first rectifies the images such that the facade is fronto-parallel. It then clusters similar features in each of the two images and matches the clusters. From them a set of hypothesized homographies of the facade is generated, using local groups of features. For each homography the epipole is recovered, yielding a fundamental matrix. For the best solution, it then decides whether the fundamental matrix has been recovered reliably and, if not, returns only the homography. The algorithm has been tested on a large number of challenging image pairs of buildings from the benchmark ZuBuD database, outperforming several state-of-the-art algorithms. PMID- 26353147 TI - Extremely Low Bit-Rate Nearest Neighbor Search Using a Set Compression Tree. AB - The goal of this work is a data structure to support approximate nearest neighbor search on very large scale sets of vector descriptors. The criteria we wish to optimize are: (i) that the memory footprint of the representation should be very small (so that it fits into main memory); and (ii) that the approximation of the original vectors should be accurate. We introduce a novel encoding method, named a Set Compression Tree (SCT), that satisfies these criteria. It is able to accurately compress 1 million descriptors using only a few bits per descriptor. The large compression rate is achieved by not compressing on a per-descriptor basis, but instead by compressing the set of descriptors jointly. We describe the encoding, decoding and use for nearest neighbor search, all of which are quite straightforward to implement. The method, tested on standard benchmarks (SIFT1M and 80 Million Tiny Images), achieves superior performance to a number of state of-the-art approaches, including Product Quantization, Locality Sensitive Hashing, Spectral Hashing, and Iterative Quantization. For example, SCT has a lower error using 5 bits than any of the other approaches, even when they use 16 or more bits per descriptor. We also include a comparison of all the above methods on the standard benchmarks. PMID- 26353148 TI - Feature Matching with Affine-Function Transformation Models. AB - Feature matching is an important problem and has extensive uses in computer vision. However, existing feature matching methods support either a specific or a small set of transformation models. In this paper, we propose a unified feature matching framework which supports a large family of transformation models. We call the family of transformation models the affine-function family, in which all transformations can be expressed by affine functions with convex constraints. In this framework, the goal is to recover transformation parameters for every feature point in a template point set to calculate their optimal matching positions in an input image. Given pairwise feature dissimilarity values between all points in the template set and the input image, we create a convex dissimilarity function for each template point. Composition of such convex functions with any transformation model in the affine-function family is shown to have an equivalent convex optimization form that can be optimized efficiently. Four example transformation models in the affine-function family are introduced to show the flexibility of our proposed framework. Our framework achieves 0.0 percent matching errors for both CMU House and Hotel sequences following the experimental setup in [6]. PMID- 26353149 TI - Image Completion Approaches Using the Statistics of Similar Patches. AB - Image completion involves filling missing parts in images. In this paper we address this problem through novel statistics of similar patches. We observe that if we match similar patches in the image and obtain their offsets (relative positions), the statistics of these offsets are sparsely distributed. We further observe that a few dominant offsets provide reliable information for completing the image. Such statistics can be incorporated into both matching-based and graph based methods for image completion. Experiments show that our method yields better results in various challenging cases, and is faster than existing state-of the-art methods. PMID- 26353150 TI - Information Theoretic Shape Matching. AB - In this paper, we describe two related algorithms that provide both rigid and non rigid point set registration with different computational complexity and accuracy. The first algorithm utilizes a nonlinear similarity measure known as correntropy. The measure combines second and high order moments in its decision statistic showing improvements especially in the presence of impulsive noise. The algorithm assumes that the correspondence between the point sets is known, which is determined with the surprise metric. The second algorithm mitigates the need to establish a correspondence by representing the point sets as probability density functions (PDF). The registration problem is then treated as a distribution alignment. The method utilizes the Cauchy-Schwarz divergence to measure the similarity/distance between the point sets and recover the spatial transformation function needed to register them. Both algorithms utilize information theoretic descriptors; however, correntropy works at the realizations level, whereas Cauchy-Schwarz divergence works at the PDF level. This allows correntropy to be less computationally expensive, and for correct correspondence, more accurate. The two algorithms are robust against noise and outliers and perform well under varying levels of distortion. They outperform several well known and state-of-the-art methods for point set registration. PMID- 26353151 TI - Latent Fingerprint Matching: Performance Gain via Feedback from Exemplar Prints. AB - Latent fingerprints serve as an important source of forensic evidence in a court of law. Automatic matching of latent fingerprints to rolled/plain (exemplar) fingerprints with high accuracy is quite vital for such applications. However, latent impressions are typically of poor quality with complex background noise which makes feature extraction and matching of latents a significantly challenging problem. We propose incorporating top-down information or feedback from an exemplar to refine the features extracted from a latent for improving latent matching accuracy. The refined latent features (e.g. ridge orientation and frequency), after feedback, are used to re-match the latent to the top K candidate exemplars returned by the baseline matcher and resort the candidate list. The contributions of this research include: (i) devising systemic ways to use information in exemplars for latent feature refinement, (ii) developing a feedback paradigm which can be wrapped around any latent matcher for improving its matching performance, and (iii) determining when feedback is actually necessary to improve latent matching accuracy. Experimental results show that integrating the proposed feedback paradigm with a state-of-the-art latent matcher improves its identification accuracy by 0.5-3.5 percent for NIST SD27 and WVU latent databases against a background database of 100k exemplars. PMID- 26353152 TI - Learning Human Actions by Combining Global Dynamics and Local Appearance. AB - In this paper, we address the problem of human action recognition through combining global temporal dynamics and local visual spatio-temporal appearance features. For this purpose, in the global temporal dimension, we propose to model the motion dynamics with robust linear dynamical systems (LDSs) and use the model parameters as motion descriptors. Since LDSs live in a non-Euclidean space and the descriptors are in non-vector form, we propose a shift invariant subspace angles based distance to measure the similarity between LDSs. In the local visual dimension, we construct curved spatio-temporal cuboids along the trajectories of densely sampled feature points and describe them using histograms of oriented gradients (HOG). The distance between motion sequences is computed with the Chi Squared histogram distance in the bag-of-words framework. Finally we perform classification using the maximum margin distance learning method by combining the global dynamic distances and the local visual distances. We evaluate our approach for action recognition on five short clips data sets, namely Weizmann, KTH, UCF sports, Hollywood2 and UCF50, as well as three long continuous data sets, namely VIRAT, ADL and CRIM13. We show competitive results as compared with current state of-the-art methods. PMID- 26353153 TI - Learning Race from Face: A Survey. AB - Faces convey a wealth of social signals, including race, expression, identity, age and gender, all of which have attracted increasing attention from multi disciplinary research, such as psychology, neuroscience, computer science, to name a few. Gleaned from recent advances in computer vision, computer graphics, and machine learning, computational intelligence based racial face analysis has been particularly popular due to its significant potential and broader impacts in extensive real-world applications, such as security and defense, surveillance, human computer interface (HCI), biometric-based identification, among others. These studies raise an important question: How implicit, non-declarative racial category can be conceptually modeled and quantitatively inferred from the face? Nevertheless, race classification is challenging due to its ambiguity and complexity depending on context and criteria. To address this challenge, recently, significant efforts have been reported toward race detection and categorization in the community. This survey provides a comprehensive and critical review of the state-of-the-art advances in face-race perception, principles, algorithms, and applications. We first discuss race perception problem formulation and motivation, while highlighting the conceptual potentials of racial face processing. Next, taxonomy of feature representational models, algorithms, performance and racial databases are presented with systematic discussions within the unified learning scenario. Finally, in order to stimulate future research in this field, we also highlight the major opportunities and challenges, as well as potentially important cross-cutting themes and research directions for the issue of learning race from face. PMID- 26353154 TI - Multi-Class Supervised Novelty Detection. AB - In this paper we study the problem of finding a support of unknown high dimensional distributions in the presence of labeling information, called Supervised Novelty Detection (SND). The One-Class Support Vector Machine (SVM) is a widely used kernel-based technique to address this problem. However with the latter approach it is difficult to model a mixture of distributions from which the support might be constituted. We address this issue by presenting a new class of SVM-like algorithms which help to approach multi-class classification and novelty detection from a new perspective. We introduce a new coupling term between classes which leverages the problem of finding a good decision boundary while preserving the compactness of a support with the l2-norm penalty. First we present our optimization objective in the primal and then derive a dual QP formulation of the problem. Next we propose a Least-Squares formulation which results in a linear system which drastically reduces computational costs. Finally we derive a Pegasos-based formulation which can effectively cope with large data sets that cannot be handled by many existing QP solvers. We complete our paper with experiments that validate the usefulness and practical importance of the proposed methods both in classification and novelty detection settings. PMID- 26353155 TI - Multilinear Discriminant Analysis for Higher-Order Tensor Data Classification. AB - In the past decade, great efforts have been made to extend linear discriminant analysis for higher-order data classification, generally referred to as multilinear discriminant analysis (MDA). Existing examples include general tensor discriminant analysis (GTDA) and discriminant analysis with tensor representation (DATER). Both the two methods attempt to resolve the problem of tensor mode dependency by iterative approximation. GTDA is known to be the first MDA method that converges over iterations. However, its performance relies highly on the tuning of the parameter in the scatter difference criterion. Although DATER usually results in better classification performance, it does not converge, yet the number of iterations executed has a direct impact on DATER's performance. In this paper, we propose a closed-form solution to the scatter difference objective in GTDA, namely, direct GTDA (DGTDA) which also gets rid of parameter tuning. We demonstrate that DGTDA outperforms GTDA in terms of both efficiency and accuracy. In addition, we propose constrained multilinear discriminant analysis (CMDA) that learns the optimal tensor subspace by iteratively maximizing the scatter ratio criterion. We prove both theoretically and experimentally that the value of the scatter ratio criterion in CMDA approaches its extreme value, if it exists, with bounded error, leading to superior and more stable performance in comparison to DATER. PMID- 26353156 TI - Object Tracking by Oversampling Local Features. AB - In this paper, we present the ALIEN tracking method that exploits oversampling of local invariant representations to build a robust object/context discriminative classifier. To this end, we use multiple instances of scale invariant local features weakly aligned along the object template. This allows taking into account the 3D shape deviations from planarity and their interactions with shadows, occlusions, and sensor quantization for which no invariant representations can be defined. A non-parametric learning algorithm based on the transitive matching property discriminates the object from the context and prevents improper object template updating during occlusion. We show that our learning rule has asymptotic stability under mild conditions and confirms the drift-free capability of the method in long-term tracking. A real-time implementation of the ALIEN tracker has been evaluated in comparison with the state-of-the-art tracking systems on an extensive set of publicly available video sequences that represent most of the critical conditions occurring in real tracking environments. We have reported superior or equal performance in most of the cases and verified tracking with no drift in very long video sequences. PMID- 26353157 TI - Word Spotting and Recognition with Embedded Attributes. AB - This paper addresses the problems of word spotting and word recognition on images. In word spotting, the goal is to find all instances of a query word in a dataset of images. In recognition, the goal is to recognize the content of the word image, usually aided by a dictionary or lexicon. We describe an approach in which both word images and text strings are embedded in a common vectorial subspace. This is achieved by a combination of label embedding and attributes learning, and a common subspace regression. In this subspace, images and strings that represent the same word are close together, allowing one to cast recognition and retrieval tasks as a nearest neighbor problem. Contrary to most other existing methods, our representation has a fixed length, is low dimensional, and is very fast to compute and, especially, to compare. We test our approach on four public datasets of both handwritten documents and natural images showing results comparable or better than the state-of-the-art on spotting and recognition tasks. PMID- 26353158 TI - Comments on "A Closed-Form Solution to Tensor Voting: Theory and Applications". AB - We comment on a paper that describes a closed-form formulation to Tensor Voting, a technique to perceptually group clouds of points, usually applied to infer features in images. The authors proved an analytic solution to the technique, a highly relevant contribution considering that the original formulation required numerical integration, a time-consuming task. Their work constitutes the first closed-form expression for the Tensor Voting framework. In this work we first observe that the proposed formulation leads to unexpected results which do not satisfy the constraints for a Tensor Voting output, hence they cannot be interpreted. Given that the closed-form expression is said to be an analytic equivalent solution, unexpected outputs should not be encountered unless there are flaws in the proof. We analyzed the underlying math to find which were the causes of these unexpected results. In this commentary we show that their proposal does not in fact provide a proper analytic solution to Tensor Voting and we indicate the flaws in the proof. PMID- 26353159 TI - Effects of wheat distillers dried grains with solubles with or without protease and beta-mannanase on the performance of turkey hen poults. AB - Expansion in bioethanol production has resulted in distillers dried grains with solubles (DDGS) being readily available as a major protein source in the poultry industry. Two experiments were conducted to investigate effects of wheat DDGS (wDDGS) and enzyme on nutrient digestibility and performance of turkey hen poults (7 to 21 d). Two starter diets (0 or 30% wDDGS) were formulated to meet or exceed the nutrient requirements for Hybrid Converter female turkeys. These diets were then mixed in different proportions to obtain 2 additional wDDGS inclusion levels (10 and 20%). In Experiment 1, 0 and 30% wDDGS diets were each subdivided into 3 portions and supplemented with no enzyme (E-), protease (P+; 0.125 g/kg) or beta mannanase (M+; 0.5 g/kg). A total of 144, 7-day-old poults were randomly distributed in groups of 4 in 6 replicate cages per treatment. There were no significant main effects or interactions on feed intake from 7 to 21 d. However, a positive (P<0.05) effect of 30% wDDGS was shown for weight gain and gain:feed. A significant interaction on nitrogen retention (NR) was found between enzymes and wDDGS level. There were significant main effects and interactions on the AME of the diets. The AME was higher (P<0.05) for 30% compared to 0% wDDGS. Supplementation of P+ decreased (P<0.05) AME for 0% diets as compared to 30% diets and vice versa for M+. In Experiment 2, 7-day-old poults (4 birds per 6 replications per treatment) were fed 4 levels of wDDGS (0, 10, 20, and 30%) with no enzyme. A linear (P<0.01) response was found for gain:feed with 30% wDDGS having a better response. Quadratic (P<0.01) responses were also found for NR and AME; both were highest for 10% wDDGS diets. In summary, no beneficial effects of P+ or M+ were demonstrated in diets containing 30% wDDGS. Wheat DDGS is a valuable energy source and as high as 30% can be incorporated in turkey hen poults (7 to 21 d) diets. PMID- 26353162 TI - Risk factors for preterm birth and new approaches to its early diagnosis. PMID- 26353161 TI - Evaluation of measured postpartum blood loss after vaginal delivery using a collector bag in relation to postpartum hemorrhage management strategies: a prospective observational study. AB - AIM: To evaluate the incidence of postpartum hemorrhage (PPH) and severe PPH via routine use of a pelvic drape to objectively measure blood loss after vaginal delivery in connection with PPH management. METHODS: This prospective observational study was undertaken at the obstetrical department of the Charite University Hospital from December 2011 to May 2013 and evaluated an unselected cohort of planned vaginal deliveries (n=1019 live singletons at term). A calibrated collecting drape was used to meassure blood loss in the third stage of labor. PPH and severe PPH were defined as blood loss >=500 mL and >=1000 mL, respectively. Maternal hemoglobin content was evaluated at admission to delivery and at the first day after childbirth. RESULTS: During the study period, 809 vaginal deliveries were analysed. Direct measurement revealed a median blood loss of 250 mL. The incidences of PPH and severe PPH were 15% and 3%, respectively. Mean maternal hemoglobin content at admission was 11.9+/-1.1 g/dL, with a mean decrease of 1.0+/-1.1 g/dL. Blood loss measured after vaginal delivery correlated significantly with maternal hemoglobin decrease. CONCLUSIONS: This study suggests that PPH incidence may be higher than indicated by population-based data. Underbuttocks drapes are simple, objective bedside tools to diagnose PPH. Blood loss should be quantified systematically if PPH is suspected. PMID- 26353164 TI - Erratum to: Impact of the nitric oxide-donor pentaerythrityl-tetranitrate on perinatal outcome in risk pregnancies: a prospective, randomized, double-blinded trial. AB - On page 1 "adjusted relative risk (RR)" should be changed to "adjusted odds ratio (OR)". On page 1, 3 and in the table head of table 2 "adjusted RR" should be changed to "adjusted OR". On page 3 "Mantel-Haenszel estimates of relative risk" should be changed to "Mantel-Haenszel estimates of odds ratios". In Table 2, caption b "Mantel-Haenszel estimate of relative risk" should be changed to "Mantel-Haenszel estimate of odds ratio". PMID- 26353165 TI - Diabetes insipidus in children. AB - Diabetes insipidus (DI) is one of the common disorders affecting sodium and water homeostasis, and results when ADH is either inadequately produced, or unable to negotiate its actions on the renal collecting tubules through aquaporins. The diagnostic algorithm starts with exclusion of other causes of polyuria and establishing low urine osmolality in the presence of high serum osmolality. In this paper, we have reviewed the diagnosis, etiology and management of DI in children, with special emphasis on recent advances in the field. PMID- 26353166 TI - Lipomatous nevus and urethral caruncle mistaken for ambiguous genitalia in a female infant. AB - We report the case of a 46,XX infant referred at 3 months of age for evaluation of ambiguous genitalia with no palpable gonads. The phallus was replaced by a homogeneous peduncular structure covered by skin, and a second peduncular structure covered by mucosa was located between the labia minora above the urethral meatus and the vaginal opening. There were no associated anomalies, and she had normal growth and neuromotor development. During surgery to remove these structures, a bifid clitoris was detected and cystoscopy and vaginoscopy revealed normal female urethra and vagina. The structure located on the phallic region was a superficial lipomatous nevus, and the other mass was a congenital urethral caruncle with ectopic migration/differentiation of colonic epithelium into ventral and anterior part of the urogenital sinus. Both genital lipomas and congenital caruncles of the female urethra are very rare and their etiology is unknown. There is no previous report of coincidence of these two rare findings in an otherwise healthy girl. PMID- 26353167 TI - Physical activity does not attenuate the relationship between daily cortisol and metabolic syndrome in obese youth. AB - OBJECTIVE: We examined the associations among daily cortisol, physical activity (MVPA) and continuous metabolic syndrome score (cMetS) in obese youth. METHODS: Fifty adolescents (mean age 14.8 +/- 1.9 years) were recruited from medical clinics. Daily MVPA (min/day) was assessed by accelerometry. Saliva was sampled at prescribed times: immediately upon waking; 30 min after waking; and 3, 6 and 9 h after waking. Fasting lipids, glucose, waist circumference and blood pressure were used to calculate a continuous metabolic syndrome score (cMetS). Multiple linear regression analysis was used to examine associations among variables. RESULTS: The mean cMetS score was 4.16 +/- 4.30 and did not differ by clinic or sex. No significant relationship was found between cortisol area under the curve (cAUC) and cMetS, nor did the interaction of MVPA with cAUC significantly predict cMetS. CONCLUSIONS: Physical activity, cortisol, and metabolic risk were not associated in this sample of obese adolescents. Future research should examine the role of insulin sensitivity in these relationships. PMID- 26353168 TI - Efficacy and safety of a single monthly dose of cholecalciferol in healthy school children. AB - BACKGROUND: This study aimed to evaluate the efficacy and safety of a single monthly dose of cholecalciferol in healthy school children. METHODS: A total of 118 children of class VI of a residential school were selected to receive vitamin D supplementation in the form of oral cholecalciferol 60,000 IU monthly. Serum calcium and 25-hydroxyvitamin D (25OHD) levels were estimated at 0 and 12 months. The proportion of subjects achieving vitamin D sufficiency was assessed. RESULTS: The mean 25OHD levels increased significantly from 12.04+/-5.27 ng/mL at baseline to 32.6+/-7.05 ng/mL after 12 months of supplementation (p<0.001). None developed hypercalcemia. CONCLUSIONS: Vitamin D supplementation in the doses of 60,000 IU monthly is a reasonable, safe and cost-effective regimen for children to attain and maintain vitamin D sufficiency. PMID- 26353169 TI - The effect of tamoxifen on pubertal bone development in adolescents with pubertal gynecomastia. AB - During puberty, estrogen has a biphasic effect on epiphyses; at low levels, it leads to an increase in height and bone mass, whereas at high levels, it leads to closure of the epiphysis. Tamoxifen is a selective estrogen receptor modulator that has been used in the treatment of pubertal gynecomastia. Although it has not been approved for this indication, studies have shown it to be both successful and safe. In males, the peak of pubertal bone development occurs during Tanner stage 3-4, which is also when pubertal gynecomastia reaches its highest prevalence. Thus tamoxifen treatment could potentially effect pubertal bone development. The aim of this study was to assess the effects of tamoxifen on bone mineral density (BMD) and skeletal maturation when used for pubertal gynecomastia. We evaluated 20 boys with pubertal gynecomastia receiving tamoxifen for at least 4 months. BMD was measured with dual-energy X-ray absorptiometry. Z score and absolute BMD (g/cm(2)) was determined at baseline and 2 months after completing tamoxifen treatment. Bone age and height was evaluated before treatment and again one year later. Using absolute BMD (g/cm(2)), the mean difference from baseline was significant between the two groups both at spine (p=0.002) and femur (p=0.001), but not with the Z-score. This result was attributed to the expected increase during puberty according to sex and age. No significant effect on skeletal maturation was found (p=1.112). We conclude that when pubertal bone development is concerned, tamoxifen is safe for the treatment of pubertal gynecomastia as neither bone mineralization nor growth potential was affected. PMID- 26353170 TI - Leptin and neuropeptide Y levels in newborns. AB - AIM: Several studies have investigated leptin and neuropeptide Y (NPY) levels in children, but the information for newborns in the literature is limited. The purpose of this study was to determine leptin and NPY levels in 14- to 28-day-old newborns. MATERIALS AND METHODS: This prospective study was performed in Ataturk University Medical Faculty Research Hospital Neonatal Clinic, Erzurum, Turkey between July and December, 2014. Sixty-two 14- to 28-day-old neonates, 26 female and 36 male, were included. Age, height, and body weight of the patients were recorded. Feeding status was also recorded. The newborns were divided into two groups--those receiving breastfeeding only and those receiving breastfeeding and formula. Plasma leptin levels were measured using enzyme amplified sensitivity immunoassay (EASIA). RESULTS: The mean leptin level in 14- to 28-day-old female neonates was 4.25 +/- 3.08 ng/mL, and the mean NPY level was 24.79 +/- 9.87 ng/mL. The mean leptin level in 14- to 28-day male neonates was 3.49 +/- 2.52 ng/mL, and the mean NPY level was 25.80 +/- 9.58 ng/mL. No significant difference was determined between leptin (p=0.228) or NPY (p=0.144) in terms of feeding status. No significant difference was also observed between the sex in terms of leptin or NPY levels (leptin p=0.775 and NPY p=0.687). CONCLUSION: There were no differences in terms of feeding status and sex in leptin and NPY levels in the neonatal period. PMID- 26353171 TI - Simultaneous occurrence of diabetic ketoacidosis, thyroid storm, and multiple cerebral infarctions due to Moyamoya disease. AB - Diabetic ketoacidosis (DKA) is one of the precipitating factors that can evoke a thyroid storm. Thyroid storm may cause cerebral ischemia in Moyamoya disease, which can coexist in patients with Graves' disease. A 16-year-old girl complaining of dizziness and palpitations visited the emergency department and was diagnosed with DKA combined with hyperthyroidism. A thyroid storm occurred 6 h after the start of DKA management. Her Burch and Wartofsky score was 65 points. Right hemiplegia developed during the thyroid storm, and brain magnetic resonance (MR) diffusion-weighted images revealed multiple acute infarcts in both hemispheres. MR angiography showed stenosis of both distal internal carotid arteries and both M1 portions of the middle cerebral arteries, consistent with Moyamoya disease. After acute management for the thyroid storm with methimazole, Lugol solution and hydrocortisone, the patient's neurological symptoms completely resolved within 1 month, and free T4 level normalized within 2 months. Thyroid storm may trigger cerebral ischemia in Moyamoya disease and lead to rapid progression of cerebrovascular occlusive disease. As a simultaneous occurrence of DKA, thyroid storm and cerebrovascular accident in Moyamoya disease highly elevates morbidity and mortality, prompt recognition and management are critical to save the patient's life. PMID- 26353172 TI - Prepubertal gynecomastia and chronic lavender exposure: report of three cases. AB - INTRODUCTION: Prepubertal gynecomastia is a rare condition characterized by the growth of breast tissue in males as a consequence of early exposure to sexual hormones. When this condition is present, pathological sources of testosterone/estrogen production, such as adrenal or gonadal tumors must be searched for. A few reports have described an association between gynecomastia and substances that produce stimulation of the estrogen receptor, such as lavender and tea tree oil. METHODS: Here we describe the cases of three boys who presented with prepubertal gynecomastia and were chronically exposed to lavender. Two of these boys were exposed to a cologne, named agua de violetas, used by Hispanic communities in the US, and in their countries of origin. RESULTS: We studied a sample of the cologne used by one of the patients. Analysis of the chemical composition of the agua de violetas cologne was performed using high performance liquid chromatography as well as off-line mass spectrometric detection. All these, combined with the physical appearance and the smell, determined that the cologne had lavender as an ingredient. CONCLUSION: Exposure to estrogenic substances, such as lavender, should be explored in children presenting with prepubertal gynecomastia/thelarche. PMID- 26353173 TI - Growth hormone and growth hormone deficiency--still a lot to learn. PMID- 26353174 TI - CXCL12/CXCR4 axis: an emerging neuromodulator in pathological pain. AB - The roles of chemokine C-X-C motif ligand 12 (CXCL12) and its receptor chemokine C-X-C motif receptor 4 (CXCR4) reveal this chemokine axis as an emerging neuromodulator in the nervous system. In the peripheral and central nervous systems, both CXCL12 and CXCR4 are expressed in various kinds of nociceptive structures, and CXCL12/CXCR4 axis possesses pronociceptive property. Recent studies have demonstrated its critical roles in the development and maintenance of pathological pain, and both neuronal and glial mechanisms are involved in this CXCL12/CXCR4 axis-mediated pain processing. In this review, we summarize the recent development of the roles and mechanisms of CXCL12/CXCR4 axis in the pathogenesis of chronic pain by sciatic nerve injury, human immunodeficiency virus-associated sensory neuropathy, diabetic neuropathy, spinal cord injury, bone cancer, opioid tolerance, or opioid-induced hyperalgesia. The potential targeting of CXCL12/CXCR4 axis as an effective and broad-spectrum pharmacological approach for chronic pain therapy was also discussed. PMID- 26353175 TI - Preface to special issue on: Adiposopathy in Cancer and (Cardio)Metabolic Diseases: an Endocrine Approach - Part 4. PMID- 26353176 TI - Reproducibility of an assay to measure serum progesterone metabolites that may be related to breast cancer risk using liquid chromatography-tandem mass spectrometry. AB - Recent data suggest a novel role of progesterone in breast cancer etiology involving the progesterone metabolites 3alpha-dihydroprogesterone (3alphaHP), 5alpha-dihydroprogesterone (5alphaP), and 20alpha-dihydroprogesterone (20alphaHP). Accurate and precise measures of progesterone metabolites are needed for etiologic studies of hormonally related cancers. We have developed a high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method to measure five hormones, including progesterone, its precursor pregnenolone, and three progesterone metabolites, 5alphaP, 3alphaHP, and 20alphaHP. Hormone levels were measured in serum from 20 healthy volunteers (7 men, 5 premenopausal women, and 8 postmenopausal women). Two blinded, randomized aliquots per individual were assayed in each of four batches. The coefficients of variation (CV) and intraclass correlation coefficients (ICC) were calculated from the individual components of variance. The overall laboratory CVs were <3% and ICCs were uniformly high (>98%) for all hormones measured across sex/menopausal status groups. Our HPLC-MS/MS assay of progesterone metabolites demonstrated excellent sensitivity, laboratory reproducibility, and interindividual variation, suggesting that this serum assay is suitable for epidemiologic research. The high sensitivity of the assay, and thus the ability to quantify concentrations among postmenopausal women and men, further supports that this novel assay is suitable for studies of serum progesterone metabolite concentrations and risk of breast cancer or other hormonally related cancer. PMID- 26353177 TI - Effect of rifampicin pretreatment on the oral bioavailability of domperidone in healthy human volunteers. AB - BACKGROUND: Increased exsorption of domperidone was observed from different parts of the small intestine of the rat after pretreatment with rifampicin by the everted sac method. Based on the in vitro studies the effect of rifampicin pretreatment on the pharmacokinetics of domperidone was investigated in eight healthy male volunteers. METHODS: After an overnight fast, 20 mg domperidone was administered to the volunteers, either alone or after 6 days pretreatment with a once daily dose of 600 mg rifampicin. Serum concentrations of domperidone were estimated by reverse phase HPLC. Pharmacokinetic parameters were determined based on non-compartmental model analysis using the computer program kinetica. RESULTS: Rifampicin pretreatment decreased Cmax, AUCo-infinity, AUMC, MRT and t1/2 by 25.11%, 37.76%, 64.97%, 43.71% and 44.48%, respectively. This may be due to increased induction of cytochrome P450 enzymes and/or increased expression of P glycoprotein. CONCLUSIONS: This interaction may have clinical significance when domperidone is co-administered with rifampicin in chronic treatment conditions, such as tuberculosis, leprosy and other infections of joints, bones, etc. PMID- 26353178 TI - Metabolic phenotype prediction from genotyping data: a bottleneck for the implementation of pharmacogenetics in drug development and clinical practice. PMID- 26353179 TI - Association of ABCB1, ABCC5 and xanthine oxidase genetic polymorphisms with methotrexate adverse reactions in Mexican pediatric patients with ALL. AB - BACKGROUND: Acute lymphoblastic leukemia (ALL) is one of the most frequent oncological disorders in pediatric populations. To date, the drug of choice for the treatment of ALL is methotrexate, a drug associated with a high risk of adverse reactions (ADRs). The xanthine oxidase (XO) polymorphisms, 1936A>G and 2107A>G, as well as the polymorphic variants derived from ATP-binding cassette transporter gene subfamilies, ABCB1 and ABCC5, of drug resistant codifying genes, are implicated as precursors of drug-related neurologic, hepatic, and renal toxicities. Our aim was to determine whether the mentioned polymorphisms are risk or protective factors for the development of adverse reactions by methotrexate in our pediatric population with ALL. METHODS: A total of 35 Mexican children from Centro Estatal de Cancerologia-Durango, Mexico, with ALL and the previously noted polymorphisms as determined qPCR were studied. At the same time, a 12-month drug monitoring program was conducted in accordance with WHO-PAHO guidelines for pharmacovigilance. RESULTS: The ABCB11936A>G and 2107A>G and ABCC5 3414+434A>C polymorphisms were not associated with methotrexate ADRs. Single nucleotide polymorphisms (SNPs) of ABCB1 1236C>T (OR 0.19, 95% CI: 0.03-0.9, p<0.05) and ABCC5 3933+313T>C (OR 0.12, 95% CI: 0.027-0.58, p<0.05) were associated with methotrexate ADRs. CONCLUSIONS: SNPs 1236C>T of ABCB1 and ABCC5 3933+313T>C are not associated with the development of typical ADRs by methotrexate, rather, they showed a protective factor for myelosuppression in the studied sick population. PMID- 26353180 TI - The D543N polymorphism of the SLC11A1/NRAMP1 gene is associated with treatment failure in male patients with pulmonary tuberculosis. AB - BACKGROUND: Polymorphisms in SLC11A1/NRAMP1 have shown an important association with susceptibility to tuberculosis and progression to active disease. However, whether there is an association of these polymorphisms with treatment failure is unknown. The aim of this study was to determine the association of SLC11A1 polymorphisms with treatment failure in Mexican subjects with pulmonary tuberculosis. METHODS: Thirty-three subjects with treatment failure were paired by age and body mass index with 33 patients who successfully completed treatment and were considered cured. We assessed the polymorphisms of SLC11A1 in the regions of D543N and INT4 via polymerase chain reaction real-time TaqMan(r) single nucleotide polymorphism (SNP) genotyping. RESULTS: We found that D543N (G/A genotype) was associated with treatment failure in patients with pulmonary tuberculosis [odds ratio (OR) 11.61, 95% confidence interval (CI) 3.66-36.78]. When adjusted by gender, this association remained significant in males (OR 11.09, 95% CI 3.46-35.51). CONCLUSIONS: In our male population, the presence of the D543N polymorphism of SLC11A1 is a risk factor for treatment failure. This finding should be confirmed in other populations. PMID- 26353181 TI - Active Batch Selection via Convex Relaxations with Guaranteed Solution Bounds. AB - Active learning techniques have gained popularity to reduce human effort in labeling data instances for inducing a classifier. When faced with large amounts of unlabeled data, such algorithms automatically identify the exemplar instances for manual annotation. More recently, there have been attempts towards a batch mode form of active learning, where a batch of data points is simultaneously selected from an unlabeled set. In this paper, we propose two novel batch mode active learning (BMAL) algorithms: BatchRank and BatchRand. We first formulate the batch selection task as an NP-hard optimization problem; we then propose two convex relaxations, one based on linear programming and the other based on semi definite programming to solve the batch selection problem. Finally, a deterministic bound is derived on the solution quality for the first relaxation and a probabilistic bound for the second. To the best of our knowledge, this is the first research effort to derive mathematical guarantees on the solution quality of the BMAL problem. Our extensive empirical studies on 15 binary, multi class and multi-label challenging datasets corroborate that the proposed algorithms perform at par with the state-of-the-art techniques, deliver high quality solutions and are robust to real-world issues like label noise and class imbalance. PMID- 26353182 TI - Color Constancy Using Double-Opponency. AB - The double-opponent (DO) color-sensitive cells in the primary visual cortex (V1) of the human visual system (HVS) have long been recognized as the physiological basis of color constancy. In this work we propose a new color constancy model by imitating the functional properties of the HVS from the single-opponent (SO) cells in the retina to the DO cells in V1 and the possible neurons in the higher visual cortexes. The idea behind the proposed double-opponency based color constancy (DOCC) model originates from the substantial observation that the color distribution of the responses of DO cells to the color-biased images coincides well with the vector denoting the light source color. Then the illuminant color is easily estimated by pooling the responses of DO cells in separate channels in LMS space with the pooling mechanism of sum or max. Extensive evaluations on three commonly used datasets, including the test with the dataset dependent optimal parameters, as well as the intra- and inter-dataset cross validation, show that our physiologically inspired DOCC model can produce quite competitive results in comparison to the state-of-the-art approaches, but with a relative simple implementation and without requiring fine-tuning of the method for each different dataset. PMID- 26353183 TI - From Intensity Profile to Surface Normal: Photometric Stereo for Unknown Light Sources and Isotropic Reflectances. AB - We propose an uncalibrated photometric stereo method that works with general and unknown isotropic reflectances. Our method uses a pixel intensity profile, which is a sequence of radiance intensities recorded at a pixel under unknown varying directional illumination. We show that for general isotropic materials and uniformly distributed light directions, the geodesic distance between intensity profiles is linearly related to the angular difference of their corresponding surface normals, and that the intensity distribution of the intensity profile reveals reflectance properties. Based on these observations, we develop two methods for surface normal estimation; one for a general setting that uses only the recorded intensity profiles, the other for the case where a BRDF database is available while the exact BRDF of the target scene is still unknown. Quantitative and qualitative evaluations are conducted using both synthetic and real-world scenes, which show the state-of-the-art accuracy of smaller than 10 degree without using reference data and 5 degree with reference data for all 100 materials in MERL database. PMID- 26353184 TI - HFirst: A Temporal Approach to Object Recognition. AB - This paper introduces a spiking hierarchical model for object recognition which utilizes the precise timing information inherently present in the output of biologically inspired asynchronous address event representation (AER) vision sensors. The asynchronous nature of these systems frees computation and communication from the rigid predetermined timing enforced by system clocks in conventional systems. Freedom from rigid timing constraints opens the possibility of using true timing to our advantage in computation. We show not only how timing can be used in object recognition, but also how it can in fact simplify computation. Specifically, we rely on a simple temporal-winner-take-all rather than more computationally intensive synchronous operations typically used in biologically inspired neural networks for object recognition. This approach to visual computation represents a major paradigm shift from conventional clocked systems and can find application in other sensory modalities and computational tasks. We showcase effectiveness of the approach by achieving the highest reported accuracy to date (97.5% +/- 3.5%) for a previously published four class card pip recognition task and an accuracy of 84.9% +/- 1.9% for a new more difficult 36 class character recognition task. PMID- 26353185 TI - Regionlets for Generic Object Detection. AB - Generic object detection is confronted by dealing with different degrees of variations, caused by viewpoints or deformations in distinct object classes, with tractable computations. This demands for descriptive and flexible object representations which can be efficiently evaluated in many locations. We propose to model an object class with a cascaded boosting classifier which integrates various types of features from competing local regions, each of which may consist of a group of subregions, named as regionlets. A regionlet is a base feature extraction region defined proportionally to a detection window at an arbitrary resolution (i.e., size and aspect ratio). These regionlets are organized in small groups with stable relative positions to be descriptive to delineate fine-grained spatial layouts inside objects. Their features are aggregated into a one dimensional feature within one group so as to be flexible to tolerate deformations. The most discriminative regionlets for each object class are selected through a boosting learning procedure. Our regionlet approach achieves very competitive performance on popular multi-class detection benchmark datasets with a single method, without any context. It achieves a detection mean average precision of 41.7 percent on the PASCAL VOC 2007 dataset, and 39.7 percent on the VOC 2010 for 20 object categories. We further develop support pixel integral images to efficiently augment regionlet features with the responses learned by deep convolutional neural networks. Our regionlet based method won second place in the ImageNet Large Scale Visual Object Recognition Challenge (ILSVRC 2013). PMID- 26353186 TI - Robust Structured Subspace Learning for Data Representation. AB - To uncover an appropriate latent subspace for data representation, in this paper we propose a novel Robust Structured Subspace Learning (RSSL) algorithm by integrating image understanding and feature learning into a joint learning framework. The learned subspace is adopted as an intermediate space to reduce the semantic gap between the low-level visual features and the high-level semantics. To guarantee the subspace to be compact and discriminative, the intrinsic geometric structure of data, and the local and global structural consistencies over labels are exploited simultaneously in the proposed algorithm. Besides, we adopt the l2,1-norm for the formulations of loss function and regularization respectively to make our algorithm robust to the outliers and noise. An efficient algorithm is designed to solve the proposed optimization problem. It is noted that the proposed framework is a general one which can leverage several well known algorithms as special cases and elucidate their intrinsic relationships. To validate the effectiveness of the proposed method, extensive experiments are conducted on diversity datasets for different image understanding tasks, i.e., image tagging, clustering, and classification, and the more encouraging results are achieved compared with some state-of-the-art approaches. PMID- 26353187 TI - Shape-from-Template. AB - We study a problem that we call Shape-from-Template, which is the problem of reconstructing the shape of a deformable surface from a single image and a 3D template. Current methods in the literature address the case of isometric deformations, and relax the isometry constraint to the convex inextensibility constraint, solved using the so-called maximum depth heuristic. We call these methods zeroth-order since they use image point locations (the zeroth-order differential structure) to solve the shape inference problem from a perspective image. We propose a novel class of methods that we call first-order. The key idea is to use both image point locations and their first-order differential structure. The latter can be easily extracted from a warp between the template and the input image. We give a unified problem formulation as a system of PDEs for isometric and conformal surfaces that we solve analytically. This has important consequences. First, it gives the first analytical algorithms to solve this type of reconstruction problems. Second, it gives the first algorithms to solve for the exact constraints. Third, it allows us to study the well-posedness of this type of reconstruction: we establish that isometric surfaces can be reconstructed unambiguously and that conformal surfaces can be reconstructed up to a few discrete ambiguities and a global scale. In the latter case, the candidate solution surfaces are obtained analytically. Experimental results on simulated and real data show that our isometric methods generally perform as well as or outperform state of the art approaches in terms of reconstruction accuracy, while our conformal methods largely outperform all isometric methods for extensible deformations. PMID- 26353188 TI - The Perturbed Variation. AB - We introduce a new discrepancy measure between two distributions that gives an indication on their similarity. The new measure, termed the Perturbed Variation (PV), gives an intuitive interpretation of similarity; it optimally perturbs the distributions so that they best fit each other. The PV is defined between continuous and discrete distributions, and can be efficiently estimated from samples. We provide bounds on the convergence of the estimated score to its distributional value, as well as robustness analysis of the PV to outliers. A number of possible applications of the score are presented, and its ability to detect similarity is compared with that of other known measures on real data. We also present a new visual tracking algorithm based on the PV, and compare its performance with known tracking algorithms. PMID- 26353189 TI - Unsupervised Discovery of Subspace Trends. AB - This paper presents unsupervised algorithms for discovering previously unknown subspace trends in high-dimensional data sets without the benefit of prior information. A subspace trend is a sustained pattern of gradual/progressive changes within an unknown subset of feature dimensions. A fundamental challenge to subspace trend discovery is the presence of irrelevant data dimensions, noise, outliers, and confusion from multiple subspace trends driven by independent factors that are mixed in with each other. These factors can obscure the trends in conventional dimension reduction & projection based data visualizations. To overcome these limitations, we propose a novel graph-theoretic neighborhood similarity measure for detecting concordant progressive changes across data dimensions. Using this measure, we present an unsupervised algorithm for trend relevant feature selection, subspace trend discovery, quantification of trend strength, and validation. Our method successfully identified verifiable subspace trends in diverse synthetic and real-world biomedical datasets. Visualizations derived from the selected trend-relevant features revealed biologically meaningful hidden subspace trend(s) that were obscured by irrelevant features and noise. Although our examples are drawn from the biological domain, the proposed algorithm is broadly applicable to exploratory analysis of high-dimensional data including visualization, hypothesis generation, knowledge discovery, and prediction in diverse other applications. PMID- 26353190 TI - A Geometric Particle Filter for Template-Based Visual Tracking. AB - Existing approaches to template-based visual tracking, in which the objective is to continuously estimate the spatial transformation parameters of an object template over video frames, have primarily been based on deterministic optimization, which as is well-known can result in convergence to local optima. To overcome this limitation of the deterministic optimization approach, in this paper we present a novel particle filtering approach to template-based visual tracking. We formulate the problem as a particle filtering problem on matrix Lie groups, specifically the three-dimensional Special Linear group SL(3) and the two dimensional affine group Aff(2). Computational performance and robustness are enhanced through a number of features: (i) Gaussian importance functions on the groups are iteratively constructed via local linearization; (ii) the inverse formulation of the Jacobian calculation is used; (iii) template resizing is performed; and (iv) parent-child particles are developed and used. Extensive experimental results using challenging video sequences demonstrate the enhanced performance and robustness of our particle filtering-based approach to template based visual tracking. We also show that our approach outperforms several state of-the-art template-based visual tracking methods via experiments using the publicly available benchmark data set. PMID- 26353191 TI - A Histogram Transform for ProbabilityDensity Function Estimation. AB - The estimation of multivariate probability density functions has traditionally been carried out by mixtures of parametric densities or by kernel density estimators. Here we present a new nonparametric approach to this problem which is based on the integration of several multivariate histograms, computed over affine transformations of the training data. Our proposal belongs to the class of averaged histogram density estimators. The inherent discontinuities of the histograms are smoothed, while their low computational complexity is retained. We provide a formal proof of the convergence to the real probability density function as the number of training samples grows, and we demonstrate the performance of our approach when compared with a set of standard probability density estimators. PMID- 26353192 TI - Background Subtraction with DirichletProcess Mixture Models. AB - Video analysis often begins with background subtraction. This problem is often approached in two steps-a background model followed by a regularisation scheme. A model of the background allows it to be distinguished on a per-pixel basis from the foreground, whilst the regularisation combines information from adjacent pixels. We present a new method based on Dirichlet process Gaussian mixture models, which are used to estimate per-pixel background distributions. It is followed by probabilistic regularisation. Using a non-parametric Bayesian method allows per-pixel mode counts to be automatically inferred, avoiding over-/under- fitting. We also develop novel model learning algorithms for continuous update of the model in a principled fashion as the scene changes. These key advantages enable us to outperform the state-of-the-art alternatives on four benchmarks. PMID- 26353193 TI - Camera Localization UsingTrajectories and Maps. AB - We propose a new Bayesian framework for automatically determining the position (location and orientation) of an uncalibrated camera using the observations of moving objects and a schematic map of the passable areas of the environment. Our approach takes advantage of static and dynamic information on the scene structures through prior probability distributions for object dynamics. The proposed approach restricts plausible positions where the sensor can be located while taking into account the inherent ambiguity of the given setting. The proposed framework samples from the posterior probability distribution for the camera position via data driven MCMC, guided by an initial geometric analysis that restricts the search space. A Kullback-Leibler divergence analysis is then used that yields the final camera position estimate, while explicitly isolating ambiguous settings. The proposed approach is evaluated in synthetic and real environments, showing its satisfactory performance in both ambiguous and unambiguous settings. PMID- 26353194 TI - Fast and Robust Recursive Algorithmsfor Separable Nonnegative Matrix Factorization. AB - In this paper, we study the nonnegative matrix factorization problem under the separability assumption (that is, there exists a cone spanned by a small subset of the columns of the input nonnegative data matrix containing all columns), which is equivalent to the hyperspectral unmixing problem under the linear mixing model and the pure-pixel assumption. We present a family of fast recursive algorithms and prove they are robust under any small perturbations of the input data matrix. This family generalizes several existing hyperspectral unmixing algorithms and hence provides for the first time a theoretical justification of their better practical performance. PMID- 26353195 TI - Jointly Learning Visually Correlated Dictionaries for Large-Scale Visual Recognition Applications. AB - Learning discriminative dictionaries for image content representation plays a critical role in visual recognition. In this paper, we present a joint dictionary learning (JDL) algorithm which exploits the inter-category visual correlations to learn more discriminative dictionaries. Given a group of visually correlated categories, JDL simultaneously learns one common dictionary and multiple category specific dictionaries to explicitly separate the shared visual atoms from the category-specific ones. The problem of JDL is formulated as a joint optimization with a discrimination promotion term according to the Fisher discrimination criterion. A visual tree method is developed to cluster a large number of categories into a set of disjoint groups, so that each of them contains a reasonable number of visually correlated categories. The process of image category clustering helps JDL to learn better dictionaries for classification by ensuring that the categories in the same group are of strong visual correlations. Also, it makes JDL to be computationally affordable in large-scale applications. Three classification schemes are adopted to make full use of the dictionaries learned by JDL for visual content representation in the task of image categorization. The effectiveness of the proposed algorithms has been evaluated using two image databases containing 17 and 1,000 categories, respectively. PMID- 26353196 TI - Non-Rigid Object Detection with LocalInterleaved Sequential Alignment (LISA). AB - This paper shows that the successively evaluated features used in a sliding window detection process to decide about object presence/absence also contain knowledge about object deformation. We exploit these detection features to estimate the object deformation. Estimated deformation is then immediately applied to not yet evaluated features to align them with the observed image data. In our approach, the alignment estimators are jointly learned with the detector. The joint process allows for the learning of each detection stage from less deformed training samples than in the previous stage. For the alignment estimation we propose regressors that approximate non-linear regression functions and compute the alignment parameters extremely fast. PMID- 26353197 TI - Optimized Product Quantization. AB - Product quantization (PQ) is an effective vector quantization method. A product quantizer can generate an exponentially large codebook at very low memory/time cost. The essence of PQ is to decompose the high-dimensional vector space into the Cartesian product of subspaces and then quantize these subspaces separately. The optimal space decomposition is important for the PQ performance, but still remains an unaddressed issue. In this paper, we optimize PQ by minimizing quantization distortions w.r.t the space decomposition and the quantization codebooks. We present two novel solutions to this challenging optimization problem. The first solution iteratively solves two simpler sub-problems. The second solution is based on a Gaussian assumption and provides theoretical analysis of the optimality. We evaluate our optimized product quantizers in three applications: (i) compact encoding for exhaustive ranking [1], (ii) building inverted multi-indexing for non-exhaustive search [2], and (iii) compacting image representations for image retrieval [3]. In all applications our optimized product quantizers outperform existing solutions. PMID- 26353198 TI - Preserving Structure in Model-Free Tracking. AB - Model-free trackers can track arbitrary objects based on a single (bounding-box) annotation of the object. Whilst the performance of model-free trackers has recently improved significantly, simultaneously tracking multiple objects with similar appearance remains very hard. In this paper, we propose a new multi object model-free tracker (using a tracking-by-detection framework) that resolves this problem by incorporating spatial constraints between the objects. The spatial constraints are learned along with the object detectors using an online structured SVM algorithm. The experimental evaluation of our structure-preserving object tracker (SPOT) reveals substantial performance improvements in multi object tracking. We also show that SPOT can improve the performance of single object trackers by simultaneously tracking different parts of the object. Moreover, we show that SPOT can be used to adapt generic, model-based object detectors during tracking to tailor them towards a specific instance of that object. PMID- 26353199 TI - Robust Recovery of Corrupted Low-RankMatrix by Implicit Regularizers. AB - Low-rank matrix recovery algorithms aim to recover a corrupted low-rank matrix with sparse errors. However, corrupted errors may not be sparse in real-world problems and the relationship between l1 regularizer on noise and robust M estimators is still unknown. This paper proposes a general robust framework for low-rank matrix recovery via implicit regularizers of robust M-estimators, which are derived from convex conjugacy and can be used to model arbitrarily corrupted errors. Based on the additive form of half-quadratic optimization, proximity operators of implicit regularizers are developed such that both low-rank structure and corrupted errors can be alternately recovered. In particular, the dual relationship between the absolute function in l1 regularizer and Huber M estimator is studied, which establishes a connection between robust low-rank matrix recovery methods and M-estimators based robust principal component analysis methods. Extensive experiments on synthetic and real-world data sets corroborate our claims and verify the robustness of the proposed framework. PMID- 26353200 TI - The Applicability of Spatiotemporal Oriented Energy Features to Region Tracking. AB - This paper proposes the novel application of an uncommonly rich feature representation to the domain of visual tracking. The proposed representation for tracking models both the spatial structure and dynamics of a target in a unified fashion, while simultaneously offering robustness to illumination variations. Specifically, the proposed feature is derived from spatiotemporal energy measurements that are computed by filtering in 3D, (x, y, t), image spacetime. These spatiotemporal energy measurements capture the underlying local spacetime orientation structure of the target across multiple scales. The breadth of applicability of these features within the field of visual tracking is demonstrated by their instantiation within three disparate tracking paradigms that are representative of the various basic types of region trackers in the field. Instantiation within these three tracking paradigms requires that the raw oriented energy measurements be post-processed using different methodologies that range from histogram accumulation to the identity transform. Qualitative and quantitative empirical evaluation on a challenging suite of videos demonstrates the strength and applicability of the proposed representation to tracking, as it outperforms other commonly-used features across all tracking paradigms. Moreover, it is shown that overall high tracking accuracy can be obtained with this proposed representation, as spatiotemporal oriented energy instantiations are shown to outperform several recent, state-of-the-art trackers. PMID- 26353201 TI - Virtual and Real World Adaptation for Pedestrian Detection. AB - Pedestrian detection is of paramount interest for many applications. Most promising detectors rely on discriminatively learnt classifiers, i.e., trained with annotated samples. However, the annotation step is a human intensive and subjective task worth to be minimized. By using virtual worlds we can automatically obtain precise and rich annotations. Thus, we face the question: can a pedestrian appearance model learnt in realistic virtual worlds work successfully for pedestrian detection in real-world images? Conducted experiments show that virtual-world based training can provide excellent testing accuracy in real world, but it can also suffer the data set shift problem as real-world based training does. Accordingly, we have designed a domain adaptation framework, V AYLA, in which we have tested different techniques to collect a few pedestrian samples from the target domain (real world) and combine them with the many examples of the source domain (virtual world) in order to train a domain adapted pedestrian classifier that will operate in the target domain. V-AYLA reports the same detection accuracy than when training with many human-provided pedestrian annotations and testing with real-world images of the same domain. To the best of our knowledge, this is the first work demonstrating adaptation of virtual and real worlds for developing an object detector. PMID- 26353202 TI - Web Image Re-Ranking UsingQuery-Specific Semantic Signatures. AB - Image re-ranking, as an effective way to improve the results of web-based image search, has been adopted by current commercial search engines such as Bing and Google. Given a query keyword, a pool of images are first retrieved based on textual information. By asking the user to select a query image from the pool, the remaining images are re-ranked based on their visual similarities with the query image. A major challenge is that the similarities of visual features do not well correlate with images' semantic meanings which interpret users' search intention. Recently people proposed to match images in a semantic space which used attributes or reference classes closely related to the semantic meanings of images as basis. However, learning a universal visual semantic space to characterize highly diverse images from the web is difficult and inefficient. In this paper, we propose a novel image re-ranking framework, which automatically offline learns different semantic spaces for different query keywords. The visual features of images are projected into their related semantic spaces to get semantic signatures. At the online stage, images are re-ranked by comparing their semantic signatures obtained from the semantic space specified by the query keyword. The proposed query-specific semantic signatures significantly improve both the accuracy and efficiency of image re-ranking. The original visual features of thousands of dimensions can be projected to the semantic signatures as short as 25 dimensions. Experimental results show that 25-40 percent relative improvement has been achieved on re-ranking precisions compared with the state-of the-art methods. PMID- 26353203 TI - Multimodal Similarity-Preserving Hashing. AB - We introduce an efficient computational framework for hashing data belonging to multiple modalities into a single representation space where they become mutually comparable. The proposed approach is based on a novel coupled siamese neural network architecture and allows unified treatment of intra- and inter-modality similarity learning. Unlike existing cross-modality similarity learning approaches, our hashing functions are not limited to binarized linear projections and can assume arbitrarily complex forms. We show experimentally that our method significantly outperforms state-of-the-art hashing approaches on multimedia retrieval tasks. PMID- 26353204 TI - A Hybrid Loss for Multiclass and Structured Prediction. AB - We propose a novel hybrid loss for multiclass and structured prediction problems that is a convex combination of a log loss for Conditional Random Fields (CRFs) and a multiclass hinge loss for Support Vector Machines (SVMs). We provide a sufficient condition for when the hybrid loss is Fisher consistent for classification. This condition depends on a measure of dominance between labels specifically, the gap between the probabilities of the best label and the second best label. We also prove Fisher consistency is necessary for parametric consistency when learning models such as CRFs. We demonstrate empirically that the hybrid loss typically performs least as well as-and often better than-both of its constituent losses on a variety of tasks, such as human action recognition. In doing so we also provide an empirical comparison of the efficacy of probabilistic and margin based approaches to multiclass and structured prediction. PMID- 26353205 TI - Contextualizing Object Detection and Classification. AB - We investigate how to iteratively and mutually boost object classification and detection performance by taking the outputs from one task as the context of the other one. While context models have been quite popular, previous works mainly concentrate on co-occurrence relationship within classes and few of them focus on contextualization from a top-down perspective, i.e. high-level task context. In this paper, our system adopts a new method for adaptive context modeling and iterative boosting. First, the contextualized support vector machine (Context SVM) is proposed, where the context takes the role of dynamically adjusting the classification score based on the sample ambiguity, and thus the context-adaptive classifier is achieved. Then, an iterative training procedure is presented. In each step, Context-SVM, associated with the output context from one task (object classification or detection), is instantiated to boost the performance for the other task, whose augmented outputs are then further used to improve the former task by Context-SVM. The proposed solution is evaluated on the object classification and detection tasks of PASCAL Visual Object Classes Challenge (VOC) 2007, 2010 and SUN09 data sets, and achieves the state-of-the-art performance. PMID- 26353206 TI - Convex Discriminative Multitask Clustering. AB - Multitask clustering tries to improve the clustering performance of multiple tasks simultaneously by taking their relationship into account. Most existing multitask clustering algorithms fall into the type of generative clustering, and none are formulated as convex optimization problems. In this paper, we propose two convex Discriminative Multitask Clustering (DMTC) objectives to address the problems. The first one aims to learn a shared feature representation, which can be seen as a technical combination of the convex multitask feature learning and the convex Multiclass Maximum Margin Clustering (M3C). The second one aims to learn the task relationship, which can be seen as a combination of the convex multitask relationship learning and M3C. The objectives of the two algorithms are solved in a uniform procedure by the efficient cutting-plane algorithm and further unified in the Bayesian framework. Experimental results on a toy problem and two benchmark data sets demonstrate the effectiveness of the proposed algorithms. PMID- 26353207 TI - Data Fusion by Matrix Factorization. AB - For most problems in science and engineering we can obtain data sets that describe the observed system from various perspectives and record the behavior of its individual components. Heterogeneous data sets can be collectively mined by data fusion. Fusion can focus on a specific target relation and exploit directly associated data together with contextual data and data about system's constraints. In the paper we describe a data fusion approach with penalized matrix tri-factorization (DFMF) that simultaneously factorizes data matrices to reveal hidden associations. The approach can directly consider any data that can be expressed in a matrix, including those from feature-based representations, ontologies, associations and networks. We demonstrate the utility of DFMF for gene function prediction task with eleven different data sources and for prediction of pharmacologic actions by fusing six data sources. Our data fusion algorithm compares favorably to alternative data integration approaches and achieves higher accuracy than can be obtained from any single data source alone. PMID- 26353208 TI - Feature Space Independent Semi-Supervised Domain Adaptation via Kernel Matching. AB - Domain adaptation methods aim to learn a good prediction model in a label-scarce target domain by leveraging labeled patterns from a related source domain where there is a large amount of labeled data. However, in many practical domain adaptation learning scenarios, the feature distribution in the source domain is different from that in the target domain. In the extreme, the two distributions could differ completely when the feature representation of the source domain is totally different from that of the target domain. To address the problems of substantial feature distribution divergence across domains and heterogeneous feature representations of different domains, we propose a novel feature space independent semi-supervised kernel matching method for domain adaptation in this work. Our approach learns a prediction function on the labeled source data while mapping the target data points to similar source data points by matching the target kernel matrix to a submatrix of the source kernel matrix based on a Hilbert Schmidt Independence Criterion. We formulate this simultaneous learning and mapping process as a non-convex integer optimization problem and present a local minimization procedure for its relaxed continuous form. We evaluate the proposed kernel matching method using both cross domain sentiment classification tasks of Amazon product reviews and cross language text classification tasks of Reuters multilingual newswire stories. Our empirical results demonstrate that the proposed kernel matching method consistently and significantly outperforms comparison methods on both cross domain classification problems with homogeneous feature spaces and cross domain classification problems with heterogeneous feature spaces. PMID- 26353209 TI - From Shading to Local Shape. AB - We develop a framework for extracting a concise representation of the shape information available from diffuse shading in a small image patch. This produces a mid-level scene descriptor, comprised of local shape distributions that are inferred separately at every image patch across multiple scales. The framework is based on a quadratic representation of local shape that, in the absence of noise, has guarantees on recovering accurate local shape and lighting. And when noise is present, the inferred local shape distributions provide useful shape information without over-committing to any particular image explanation. These local shape distributions naturally encode the fact that some smooth diffuse regions are more informative than others, and they enable efficient and robust reconstruction of object-scale shape. Experimental results show that this approach to surface reconstruction compares well against the state-of-art on both synthetic images and captured photographs. PMID- 26353210 TI - Gentle Nearest Neighbors Boosting over Proper Scoring Rules. AB - Tailoring nearest neighbors algorithms to boosting is an important problem. Recent papers study an approach, UNN, which provably minimizes particular convex surrogates under weak assumptions. However, numerical issues make it necessary to experimentally tweak parts of the UNN algorithm, at the possible expense of the algorithm's convergence and performance. In this paper, we propose a lightweight Newton-Raphson alternative optimizing proper scoring rules from a very broad set, and establish formal convergence rates under the boosting framework that compete with those known for UNN. To the best of our knowledge, no such boosting compliant convergence rates were previously known in the popular Gentle Adaboost's lineage. We provide experiments on a dozen domains, including Caltech and SUN computer vision databases, comparing our approach to major families including support vector machines, (Ada)boosting and stochastic gradient descent. They support three major conclusions: (i) GNNB significantly outperforms UNN, in terms of convergence rate and quality of the outputs, (ii) GNNB performs on par with or better than computationally intensive large margin approaches, (iii) on large domains that rule out those latter approaches for computational reasons, GNNB provides a simple and competitive contender to stochastic gradient descent. Experiments include a divide-and-conquer improvement of GNNB exploiting the link with proper scoring rules optimization. PMID- 26353211 TI - Learning Separable Filters. AB - Learning filters to produce sparse image representations in terms of over complete dictionaries has emerged as a powerful way to create image features for many different purposes. Unfortunately, these filters are usually both numerous and non-separable, making their use computationally expensive. In this paper, we show that such filters can be computed as linear combinations of a smaller number of separable ones, thus greatly reducing the computational complexity at no cost in terms of performance. This makes filter learning approaches practical even for large images or 3D volumes, and we show that we significantly outperform state-of the-art methods on the curvilinear structure extraction task, in terms of both accuracy and speed. Moreover, our approach is general and can be used on generic convolutional filter banks to reduce the complexity of the feature extraction step. PMID- 26353212 TI - Lift: Multi-Label Learning with Label-Specific Features. AB - Multi-label learning deals with the problem where each example is represented by a single instance (feature vector) while associated with a set of class labels. Existing approaches learn from multi-label data by manipulating with identical feature set, i.e. the very instance representation of each example is employed in the discrimination processes of all class labels. However, this popular strategy might be suboptimal as each label is supposed to possess specific characteristics of its own. In this paper, another strategy to learn from multi-label data is studied, where label-specific features are exploited to benefit the discrimination of different class labels. Accordingly, an intuitive yet effective algorithm named LIFT, i.e. multi-label learning with Label specific Features, is proposed. LIFT firstly constructs features specific to each label by conducting clustering analysis on its positive and negative instances, and then performs training and testing by querying the clustering results. Comprehensive experiments on a total of 17 benchmark data sets clearly validate the superiority of LIFT against other well-established multi-label learning algorithms as well as the effectiveness of label-specific features. PMID- 26353213 TI - Matrix Completion for Weakly-Supervised Multi-Label Image Classification. AB - In the last few years, image classification has become an incredibly active research topic, with widespread applications. Most methods for visual recognition are fully supervised, as they make use of bounding boxes or pixelwise segmentations to locate objects of interest. However, this type of manual labeling is time consuming, error prone and it has been shown that manual segmentations are not necessarily the optimal spatial enclosure for object classifiers. This paper proposes a weakly-supervised system for multi-label image classification. In this setting, training images are annotated with a set of keywords describing their contents, but the visual concepts are not explicitly segmented in the images. We formulate the weakly-supervised image classification as a low-rank matrix completion problem. Compared to previous work, our proposed framework has three advantages: (1) Unlike existing solutions based on multiple instance learning methods, our model is convex. We propose two alternative algorithms for matrix completion specifically tailored to visual data, and prove their convergence. (2) Unlike existing discriminative methods, our algorithm is robust to labeling errors, background noise and partial occlusions. (3) Our method can potentially be used for semantic segmentation. Experimental validation on several data sets shows that our method outperforms state-of-the-art classification algorithms, while effectively capturing each class appearance. PMID- 26353214 TI - Rank-Based Similarity Search: Reducing the Dimensional Dependence. AB - This paper introduces a data structure for k-NN search, the Rank Cover Tree (RCT), whose pruning tests rely solely on the comparison of similarity values; other properties of the underlying space, such as the triangle inequality, are not employed. Objects are selected according to their ranks with respect to the query object, allowing much tighter control on the overall execution costs. A formal theoretical analysis shows that with very high probability, the RCT returns a correct query result in time that depends very competitively on a measure of the intrinsic dimensionality of the data set. The experimental results for the RCT show that non-metric pruning strategies for similarity search can be practical even when the representational dimension of the data is extremely high. They also show that the RCT is capable of meeting or exceeding the level of performance of state-of-the-art methods that make use of metric pruning or other selection tests involving numerical constraints on distance values. PMID- 26353215 TI - Shape Matching Using Multiscale Integral Invariants. AB - We present a shape descriptor based on integral kernels. Shape is represented in an implicit form and it is characterized by a series of isotropic kernels that provide desirable invariance properties. The shape features are characterized at multiple scales which form a signature that is a compact description of shape over a range of scales. The shape signature is designed to be invariant with respect to group transformations which include translation, rotation, scaling, and reflection. In addition, the integral kernels that characterize local shape geometry enable the shape signature to be robust with respect to undesirable perturbations while retaining discriminative power. Use of our shape signature is demonstrated for shape matching based on a number of synthetic and real examples. PMID- 26353216 TI - Tangent Bundle Elastica and Computer Vision. AB - Visual curve completion, an early visual process that completes the occluded parts between observed boundary fragments (a.k.a. inducers), is a major problem in perceptual organization and a critical step toward higher level visual tasks in both biological and machine vision. Most computational contributions to solving this problem suggest desired perceptual properties that the completed contour should satisfy in the image plane, and then seek the mathematical curves that provide them. Alternatively, few studies (including by the authors) have suggested to frame the problem not in the image plane but rather in the unit tangent bundleR (2) * S(1), the space that abstracts the primary visual cortex, where curve completion allegedly occurs. Combining both schools, here we propose and develop a biologically plausible theory of elastica in the tangent bundle that provides not only perceptually superior completion results but also a rigorous computational prediction that inducer curvatures greatly affects the shape of the completed curve, as indeed indicated by human perception. PMID- 26353217 TI - Towards Making Unlabeled Data Never Hurt. AB - It is usually expected that learning performance can be improved by exploiting unlabeled data, particularly when the number of labeled data is limited. However, it has been reported that, in some cases existing semi-supervised learning approaches perform even worse than supervised ones which only use labeled data. For this reason, it is desirable to develop safe semi-supervised learning approaches that will not significantly reduce learning performance when unlabeled data are used. This paper focuses on improving the safeness of semi-supervised support vector machines (S3VMs). First, the S3VM-us approach is proposed. It employs a conservative strategy and uses only the unlabeled instances that are very likely to be helpful, while avoiding the use of highly risky ones. This approach improves safeness but its performance improvement using unlabeled data is often much smaller than S3VMs. In order to develop a safe and well-performing approach, we examine the fundamental assumption of S3VMs, i.e., low-density separation. Based on the observation that multiple good candidate low-density separators may be identified from training data, safe semi-supervised support vector machines (S4VMs) are here proposed. This approach uses multiple low density separators to approximate the ground-truth decision boundary and maximizes the improvement in performance of inductive SVMs for any candidate separator. Under the assumption employed by S3VMs, it is here shown that S4VMs are provably safe and that the performance improvement using unlabeled data can be maximized. An out-of-sample extension of S4VMs is also presented. This extension allows S4VMs to make predictions on unseen instances. Our empirical study on a broad range of data shows that the overall performance of S4VMs is highly competitive with S3VMs, whereas in contrast to S3VMs which hurt performance significantly in many cases, S4VMs rarely perform worse than inductive SVMs. PMID- 26353218 TI - Data-Driven Objectness. AB - We propose a data-driven approach to estimate the likelihood that an image segment corresponds to a scene object (its "objectness") by comparing it to a large collection of example object regions. We demonstrate that when the application domain is known, for example, in our case activity of daily living (ADL), we can capture the regularity of the domain specific objects using millions of exemplar object regions. Our approach to estimating the objectness of an image region proceeds in two steps: 1) finding the exemplar regions that are the most similar to the input image segment; 2) calculating the objectness of the image segment by combining segment properties, mutual consistency across the nearest exemplar regions, and the prior probability of each exemplar region. In previous work, parametric objectness models were built from a small number of manually annotated objects regions, instead, our data-driven approach uses 5 million object regions along with their metadata information. Results on multiple data sets demonstrates our data-driven approach compared to the existing model based techniques. We also show the application of our approach in improving the performance of object discovery algorithms. PMID- 26353219 TI - Low Bias Local Intrinsic Dimension Estimation from Expected Simplex Skewness. AB - In exploratory high-dimensional data analysis, local intrinsic dimension estimation can sometimes be used in order to discriminate between data sets sampled from different low-dimensional structures. Global intrinsic dimension estimators can in many cases be adapted to local estimation, but this leads to problems with high negative bias or high variance. We introduce a method that exploits the curse/blessing of dimensionality and produces local intrinsic dimension estimators that have very low bias, even in cases where the intrinsic dimension is higher than the number of data points, in combination with relatively low variance. We show that our estimators have a very good ability to classify local data sets by their dimension compared to other local intrinsic dimension estimators; furthermore we provide examples showing the usefulness of local intrinsic dimension estimation in general and our method in particular for stratification of real data sets. PMID- 26353220 TI - Automatic Upright Adjustment of Photographs With Robust Camera Calibration. AB - Man-made structures often appear to be distorted in photos captured by casual photographers, as the scene layout often conflicts with how it is expected by human perception. In this paper, we propose an automatic approach for straightening up slanted man-made structures in an input image to improve its perceptual quality. We call this type of correction upright adjustment. We propose a set of criteria for upright adjustment based on human perception studies, and develop an optimization framework which yields an optimal homography for adjustment. We also develop a new optimization-based camera calibration method that performs favorably to previous methods and allows the proposed system to work reliably for a wide range of images. The effectiveness of our system is demonstrated by both quantitative comparisons and qualitative user study. PMID- 26353221 TI - Domain Anomaly Detection in Machine Perception: A System Architecture and Taxonomy. AB - We address the problem of anomaly detection in machine perception. The concept of domain anomaly is introduced as distinct from the conventional notion of anomaly used in the literature. We propose a unified framework for anomaly detection which exposes the multifaceted nature of anomalies and suggest effective mechanisms for identifying and distinguishing each facet as instruments for domain anomaly detection. The framework draws on the Bayesian probabilistic reasoning apparatus which clearly defines concepts such as outlier, noise, distribution drift, novelty detection (object, object primitive), rare events, and unexpected events. Based on these concepts we provide a taxonomy of domain anomaly events. One of the mechanisms helping to pinpoint the nature of anomaly is based on detecting incongruence between contextual and noncontextual sensor(y) data interpretation. The proposed methodology has wide applicability. It underpins in a unified way the anomaly detection applications found in the literature. To illustrate some of its distinguishing features, in here the domain anomaly detection methodology is applied to the problem of anomaly detection for a video annotation system. PMID- 26353222 TI - Exemplar-Based Color Constancy and Multiple Illumination. AB - Exemplar-based learning or, equally, nearest neighbor methods have recently gained interest from researchers in a variety of computer science domains because of the prevalence of large amounts of accessible data and storage capacity. In computer vision, these types of technique have been successful in several problems such as scene recognition, shape matching, image parsing, character recognition, and object detection. Applying the concept of exemplar-based learning to the problem of color constancy seems odd at first glance since, in the first place, similar nearest neighbor images are not usually affected by precisely similar illuminants and, in the second place, gathering a dataset consisting of all possible real-world images, including indoor and outdoor scenes and for all possible illuminant colors and intensities, is indeed impossible. In this paper, we instead focus on surfaces in the image and address the color constancy problem by unsupervised learning of an appropriate model for each training surface in training images. We find nearest neighbor models for each surface in a test image and estimate its illumination based on comparing the statistics of pixels belonging to nearest neighbor surfaces and the target surface. The final illumination estimation results from combining these estimated illuminants over surfaces to generate a unique estimate. We show that it performs very well, for standard datasets, compared to current color constancy algorithms, including when learning based on one image dataset is applied to tests from a different dataset. The proposed method has the advantage of overcoming multi illuminant situations, which is not possible for most current methods since they assume the color of the illuminant is constant all over the image. We show a technique to overcome the multiple illuminant situation using the proposed method and test our technique on images with two distinct sources of illumination using a multiple-illuminant color constancy dataset. The concept proposed here is a completely new approach to the color constancy problem and provides a simple learning-based framework. PMID- 26353223 TI - From Bits to Images: Inversion of Local Binary Descriptors. AB - Local Binary Descriptors are becoming more and more popular for image matching tasks, especially when going mobile. While they are extensively studied in this context, their ability to carry enough information in order to infer the original image is seldom addressed. In this work, we leverage an inverse problem approach to show that it is possible to directly reconstruct the image content from Local Binary Descriptors. This process relies on very broad assumptions besides the knowledge of the pattern of the descriptor at hand. This generalizes previous results that required either a prior learning database or non-binarized features. Furthermore, our reconstruction scheme reveals differences in the way different Local Binary Descriptors capture and encode image information. Hence, the potential applications of our work are multiple, ranging from privacy issues caused by eavesdropping image keypoints streamed by mobile devices to the design of better descriptors through the visualization and the analysis of their geometric content. PMID- 26353224 TI - Gaussian Process-Mixture Conditional Heteroscedasticity. AB - Generalized autoregressive conditional heteroscedasticity (GARCH) models have long been considered as one of the most successful families of approaches for volatility modeling in financial return series. In this paper, we propose an alternative approach based on methodologies widely used in the field of statistical machine learning. Specifically, we propose a novel nonparametric Bayesian mixture of Gaussian process regression models, each component of which models the noise variance process that contaminates the observed data as a separate latent Gaussian process driven by the observed data. This way, we essentially obtain a Gaussian process-mixture conditional heteroscedasticity (GPMCH) model for volatility modeling in financial return series. We impose a nonparametric prior with power-law nature over the distribution of the model mixture components, namely the Pitman-Yor process prior, to allow for better capturing modeled data distributions with heavy tails and skewness. Finally, we provide a copula-based approach for obtaining a predictive posterior for the covariances over the asset returns modeled by means of a postulated GPMCH model. We evaluate the efficacy of our approach in a number of benchmark scenarios, and compare its performance to state-of-the-art methodologies. PMID- 26353225 TI - Geodesic Mapping for Dynamic Surface Alignment. AB - This paper presents a novel approach that achieves dynamic surface alignment by geodesing mapping. The surfaces are 3D manifold meshes representing non-rigid objects in motion (e.g., humans) which can be obtained by multiview stereo reconstruction. The proposed framework consists of a geodesic mapping (i.e., geodesic diffeomorphism) between surfaces which carry a distance function (namely the global geodesic distance), and a geodesic-based coordinate system (namely the global geodesic coordinates) defined similarly to generalized barycentric coordinates. The coordinates are used to recursively choose correspondence points in non-ambiguous regions using a coarse-to-fine strategy to reliably locate all surface points and define a discrete mapping. Complete point-to-point surface alignment with smooth mapping is then derived by optimizing a piecewise objective function within a probabilistic framework. The proposed technique only relies on surface intrinsic geometrical properties, and does not require prior knowledge on surface appearance (e.g., color or texture), shape (e.g., topology) or parameterization (e.g., mesh connectivity or complexity). The method can be used for numerous applications, such as visual information (e.g., texture) transfer between surface models representing different objects, dense motion flow estimation of 3D dynamic surfaces, wide-timeframe matching, etc. Experiments show compelling results on challenging publicly available real-world datasets. PMID- 26353226 TI - Learning Actionlet Ensemble for 3D Human Action Recognition. AB - Human action recognition is an important yet challenging task. Human actions usually involve human-object interactions, highly articulated motions, high intra class variations, and complicated temporal structures. The recently developed commodity depth sensors open up new possibilities of dealing with this problem by providing 3D depth data of the scene. This information not only facilitates a rather powerful human motion capturing technique, but also makes it possible to efficiently model human-object interactions and intra-class variations. In this paper, we propose to characterize the human actions with a novel actionlet ensemble model, which represents the interaction of a subset of human joints. The proposed model is robust to noise, invariant to translational and temporal misalignment, and capable of characterizing both the human motion and the human object interactions. We evaluate the proposed approach on three challenging action recognition datasets captured by Kinect devices, a multiview action recognition dataset captured with Kinect device, and a dataset captured by a motion capture system. The experimental evaluations show that the proposed approach achieves superior performance to the state-of-the-art algorithms. PMID- 26353227 TI - Learning Categories From Few Examples With Multi Model Knowledge Transfer. AB - Learning a visual object category from few samples is a compelling and challenging problem. In several real-world applications collecting many annotated data is costly and not always possible. However, a small training set does not allow to cover the high intraclass variability typical of visual objects. In this condition, machine learning methods provide very few guarantees. This paper presents a discriminative model adaptation algorithm able to proficiently learn a target object with few examples by relying on other previously learned source categories. The proposed method autonomously chooses from where and how much to transfer information by solving a convex optimization problem which ensures to have the minimal leave-one-out error on the available training set. We analyze several properties of the described approach and perform an extensive experimental comparison with other existing transfer solutions, consistently showing the value of our algorithm. PMID- 26353228 TI - Learning Nonlinear Functions Using Regularized Greedy Forest. AB - We consider the problem of learning a forest of nonlinear decision rules with general loss functions. The standard methods employ boosted decision trees such as Adaboost for exponential loss and Friedman's gradient boosting for general loss. In contrast to these traditional boosting algorithms that treat a tree learner as a black box, the method we propose directly learns decision forests via fully-corrective regularized greedy search using the underlying forest structure. Our method achieves higher accuracy and smaller models than gradient boosting on many of the datasets we have tested on. PMID- 26353229 TI - Localized Dictionaries Based Orientation Field Estimation for Latent Fingerprints. AB - Dictionary based orientation field estimation approach has shown promising performance for latent fingerprints. In this paper, we seek to exploit stronger prior knowledge of fingerprints in order to further improve the performance. Realizing that ridge orientations at different locations of fingerprints have different characteristics, we propose a localized dictionaries-based orientation field estimation algorithm, in which noisy orientation patch at a location output by a local estimation approach is replaced by real orientation patch in the local dictionary at the same location. The precondition of applying localized dictionaries is that the pose of the latent fingerprint needs to be estimated. We propose a Hough transform-based fingerprint pose estimation algorithm, in which the predictions about fingerprint pose made by all orientation patches in the latent fingerprint are accumulated. Experimental results on challenging latent fingerprint datasets show the proposed method outperforms previous ones markedly. PMID- 26353230 TI - Robust Text Detection in Natural Scene Images. AB - Text detection in natural scene images is an important prerequisite for many content-based image analysis tasks. In this paper, we propose an accurate and robust method for detecting texts in natural scene images. A fast and effective pruning algorithm is designed to extract Maximally Stable Extremal Regions (MSERs) as character candidates using the strategy of minimizing regularized variations. Character candidates are grouped into text candidates by the single link clustering algorithm, where distance weights and clustering threshold are learned automatically by a novel self-training distance metric learning algorithm. The posterior probabilities of text candidates corresponding to non text are estimated with a character classifier; text candidates with high non text probabilities are eliminated and texts are identified with a text classifier. The proposed system is evaluated on the ICDAR 2011 Robust Reading Competition database; the f-measure is over 76%, much better than the state-of the-art performance of 71%. Experiments on multilingual, street view, multi orientation and even born-digital databases also demonstrate the effectiveness of the proposed method. PMID- 26353231 TI - Support Vector Machine Classifier With Pinball Loss. AB - Traditionally, the hinge loss is used to construct support vector machine (SVM) classifiers. The hinge loss is related to the shortest distance between sets and the corresponding classifier is hence sensitive to noise and unstable for re sampling. In contrast, the pinball loss is related to the quantile distance and the result is less sensitive. The pinball loss has been deeply studied and widely applied in regression but it has not been used for classification. In this paper, we propose a SVM classifier with the pinball loss, called pin-SVM, and investigate its properties, including noise insensitivity, robustness, and misclassification error. Besides, insensitive zone is applied to the pin-SVM for a sparse model. Compared to the SVM with the hinge loss, the proposed pin-SVM has the same computational complexity and enjoys noise insensitivity and re-sampling stability. PMID- 26353232 TI - 2D Affine and Projective Shape Analysis. AB - Current techniques for shape analysis tend to seek invariance to similarity transformations (rotation, translation, and scale), but certain imaging situations require invariance to larger groups, such as affine or projective groups. Here we present a general Riemannian framework for shape analysis of planar objects where metrics and related quantities are invariant to affine and projective groups. Highlighting two possibilities for representing object boundaries-ordered points (or landmarks) and parameterized curves-we study different combinations of these representations (points and curves) and transformations (affine and projective). Specifically, we provide solutions to three out of four situations and develop algorithms for computing geodesics and intrinsic sample statistics, leading up to Gaussian-type statistical models, and classifying test shapes using such models learned from training data. In the case of parameterized curves, we also achieve the desired goal of invariance to re parameterizations. The geodesics are constructed by particularizing the path straightening algorithm to geometries of current manifolds and are used, in turn, to compute shape statistics and Gaussian-type shape models. We demonstrate these ideas using a number of examples from shape and activity recognition. PMID- 26353233 TI - 3D Traffic Scene Understanding From Movable Platforms. AB - In this paper, we present a novel probabilistic generative model for multi-object traffic scene understanding from movable platforms which reasons jointly about the 3D scene layout as well as the location and orientation of objects in the scene. In particular, the scene topology, geometry, and traffic activities are inferred from short video sequences. Inspired by the impressive driving capabilities of humans, our model does not rely on GPS, lidar, or map knowledge. Instead, it takes advantage of a diverse set of visual cues in the form of vehicle tracklets, vanishing points, semantic scene labels, scene flow, and occupancy grids. For each of these cues, we propose likelihood functions that are integrated into a probabilistic generative model. We learn all model parameters from training data using contrastive divergence. Experiments conducted on videos of 113 representative intersections show that our approach successfully infers the correct layout in a variety of very challenging scenarios. To evaluate the importance of each feature cue, experiments using different feature combinations are conducted. Furthermore, we show how by employing context derived from the proposed method we are able to improve over the state-of-the-art in terms of object detection and object orientation estimation in challenging and cluttered urban environments. PMID- 26353234 TI - Hardware-Efficient Bilateral Filtering for Stereo Matching. AB - This paper presents a new bilateral filtering method specially designed for practical stereo vision systems. Parallel algorithms are preferred in these systems due to the real-time performance requirement. Edge-preserving filters like the bilateral filter have been demonstrated to be very effective for high quality local stereo matching. A hardware-efficient bilateral filter is thus proposed in this paper. When moved to an NVIDIA GeForce GTX 580 GPU, it can process a one megapixel color image at around 417 frames per second. This filter can be directly used for cost aggregation required in any local stereo matching algorithm. Quantitative evaluation shows that it outperforms all the other local stereo methods both in terms of accuracy and speed on Middlebury benchmark. It ranks 12th out of over 120 methods on Middlebury data sets, and the average runtime (including the matching cost computation, occlusion handling, and post processing) is only 15 milliseconds (67 frames per second). PMID- 26353235 TI - Local Pyramidal Descriptors for Image Recognition. AB - In this paper, we present a novel method to improve the flexibility of descriptor matching for image recognition by using local multiresolution pyramids in feature space. We propose that image patches be represented at multiple levels of descriptor detail and that these levels be defined in terms of local spatial pooling resolution. Preserving multiple levels of detail in local descriptors is a way of hedging one's bets on which levels will most relevant for matching during learning and recognition. We introduce the Pyramid SIFT (P-SIFT) descriptor and show that its use in four state-of-the-art image recognition pipelines improves accuracy and yields state-of-the-art results. Our technique is applicable independently of spatial pyramid matching and we show that spatial pyramids can be combined with local pyramids to obtain further improvement. We achieve state-of-the-art results on Caltech-101 (80.1%) and Caltech-256 (52.6%) when compared to other approaches based on SIFT features over intensity images. Our technique is efficient and is extremely easy to integrate into image recognition pipelines. PMID- 26353236 TI - Using Actual and Imagined Walking Related Desynchronization Features in a BCI. AB - Recently, brain-computer interface (BCI) research has extended to investigate its possible use in motor rehabilitation. Most of these investigations have focused on the upper body. Only few studies consider gait because of the difficulty of recording EEG during gross movements. However, for stroke patients the rehabilitation of gait is of crucial importance. Therefore, this study investigates if a BCI can be based on walking related desynchronization features. Furthermore, the influence of complexity of the walking movements on the classification performance is investigated. Two BCI experiments were conducted in which healthy subjects performed a cued walking task, a more complex walking task (backward or adaptive walking), and imagination of the same tasks. EEG data during these tasks was classified into walking and no-walking. The results from both experiments show that despite the automaticity of walking and recording difficulties, brain signals related to walking could be classified rapidly and reliably. Classification performance was higher for actual walking movements than for imagined walking movements. There was no significant increase in classification performance for both the backward and adaptive walking tasks compared with the cued walking tasks. These results are promising for developing a BCI for the rehabilitation of gait. PMID- 26353237 TI - Are Gibbs-Type Priors the Most Natural Generalization of the Dirichlet Process? AB - Discrete random probability measures and the exchangeable random partitions they induce are key tools for addressing a variety of estimation and prediction problems in Bayesian inference. Here we focus on the family of Gibbs-type priors, a recent elegant generalization of the Dirichlet and the Pitman-Yor process priors. These random probability measures share properties that are appealing both from a theoretical and an applied point of view: (i) they admit an intuitive predictive characterization justifying their use in terms of a precise assumption on the learning mechanism; (ii) they stand out in terms of mathematical tractability; (iii) they include several interesting special cases besides the Dirichlet and the Pitman-Yor processes. The goal of our paper is to provide a systematic and unified treatment of Gibbs-type priors and highlight their implications for Bayesian nonparametric inference. We deal with their distributional properties, the resulting estimators, frequentist asymptotic validation and the construction of time-dependent versions. Applications, mainly concerning mixture models and species sampling, serve to convey the main ideas. The intuition inherent to this class of priors and the neat results they lead to make one wonder whether it actually represents the most natural generalization of the Dirichlet process. PMID- 26353238 TI - Differential Topic Models. AB - In applications we may want to compare different document collections: they could have shared content but also different and unique aspects in particular collections. This task has been called comparative text mining or cross collection modeling. We present a differential topic model for this application that models both topic differences and similarities. For this we use hierarchical Bayesian nonparametric models. Moreover, we found it was important to properly model power-law phenomena in topic-word distributions and thus we used the full Pitman-Yor process rather than just a Dirichlet process. Furthermore, we propose the transformed Pitman-Yor process (TPYP) to incorporate prior knowledge such as vocabulary variations in different collections into the model. To deal with the non-conjugate issue between model prior and likelihood in the TPYP, we thus propose an efficient sampling algorithm using a data augmentation technique based on the multinomial theorem. Experimental results show the model discovers interesting aspects of different collections. We also show the proposed MCMC based algorithm achieves a dramatically reduced test perplexity compared to some existing topic models. Finally, we show our model outperforms the state-of-the art for document classification/ideology prediction on a number of text collections. PMID- 26353239 TI - The Supervised Hierarchical Dirichlet Process. AB - We propose the supervised hierarchical Dirichlet process (sHDP), a nonparametric generative model for the joint distribution of a group of observations and a response variable directly associated with that whole group. We compare the sHDP with another leading method for regression on grouped data, the supervised latent Dirichlet allocation (sLDA) model. We evaluate our method on two real-world classification problems and two real-world regression problems. Bayesian nonparametric regression models based on the Dirichlet process, such as the Dirichlet process-generalised linear models (DP-GLM) have previously been explored; these models allow flexibility in modelling nonlinear relationships. However, until now, hierarchical Dirichlet process (HDP) mixtures have not seen significant use in supervised problems with grouped data since a straightforward application of the HDP on the grouped data results in learnt clusters that are not predictive of the responses. The sHDP solves this problem by allowing for clusters to be learnt jointly from the group structure and from the label assigned to each group. PMID- 26353240 TI - Nested Hierarchical Dirichlet Processes. AB - We develop a nested hierarchical Dirichlet process (nHDP) for hierarchical topic modeling. The nHDP generalizes the nested Chinese restaurant process (nCRP) to allow each word to follow its own path to a topic node according to a per document distribution over the paths on a shared tree. This alleviates the rigid, single-path formulation assumed by the nCRP, allowing documents to easily express complex thematic borrowings. We derive a stochastic variational inference algorithm for the model, which enables efficient inference for massive collections of text documents. We demonstrate our algorithm on 1.8 million documents from The New York Times and 2.7 million documents from Wikipedia. PMID- 26353241 TI - Pitman Yor Diffusion Trees for Bayesian Hierarchical Clustering. AB - In this paper we introduce the Pitman Yor Diffusion Tree (PYDT), a Bayesian non parametric prior over tree structures which generalises the Dirichlet Diffusion Tree [30] and removes the restriction to binary branching structure. The generative process is described and shown to result in an exchangeable distribution over data points. We prove some theoretical properties of the model including showing its construction as the continuum limit of a nested Chinese restaurant process model. We then present two alternative MCMC samplers which allow us to model uncertainty over tree structures, and a computationally efficient greedy Bayesian EM search algorithm. Both algorithms use message passing on the tree structure. The utility of the model and algorithms is demonstrated on synthetic and real world data, both continuous and binary. PMID- 26353242 TI - Combinatorial Clustering and the Beta Negative Binomial Process. AB - We develop a Bayesian nonparametric approach to a general family of latent class problems in which individuals can belong simultaneously to multiple classes and where each class can be exhibited multiple times by an individual. We introduce a combinatorial stochastic process known as the negative binomial process ( NBP ) as an infinite-dimensional prior appropriate for such problems. We show that the NBP is conjugate to the beta process, and we characterize the posterior distribution under the beta-negative binomial process ( BNBP) and hierarchical models based on the BNBP (the HBNBP). We study the asymptotic properties of the BNBP and develop a three-parameter extension of the BNBP that exhibits power-law behavior. We derive MCMC algorithms for posterior inference under the HBNBP , and we present experiments using these algorithms in the domains of image segmentation, object recognition, and document analysis. PMID- 26353243 TI - Negative Binomial Process Count and Mixture Modeling. AB - The seemingly disjoint problems of count and mixture modeling are united under the negative binomial (NB) process. A gamma process is employed to model the rate measure of a Poisson process, whose normalization provides a random probability measure for mixture modeling and whose marginalization leads to an NB process for count modeling. A draw from the NB process consists of a Poisson distributed finite number of distinct atoms, each of which is associated with a logarithmic distributed number of data samples. We reveal relationships between various count and mixture-modeling distributions and construct a Poisson-logarithmic bivariate distribution that connects the NB and Chinese restaurant table distributions. Fundamental properties of the models are developed, and we derive efficient Bayesian inference. It is shown that with augmentation and normalization, the NB process and gamma-NB process can be reduced to the Dirichlet process and hierarchical Dirichlet process, respectively. These relationships highlight theoretical, structural, and computational advantages of the NB process. A variety of NB processes, including the beta-geometric, beta-NB, marked-beta-NB, marked-gamma-NB and zero-inflated-NB processes, with distinct sharing mechanisms, are also constructed. These models are applied to topic modeling, with connections made to existing algorithms under Poisson factor analysis. Example results show the importance of inferring both the NB dispersion and probability parameters. PMID- 26353244 TI - Latent IBP Compound Dirichlet Allocation. AB - We introduce the four-parameter IBP compound Dirichlet process (ICDP), a stochastic process that generates sparse non-negative vectors with potentially an unbounded number of entries. If we repeatedly sample from the ICDP we can generate sparse matrices with an infinite number of columns and power-law characteristics. We apply the four-parameter ICDP to sparse nonparametric topic modelling to account for the very large number of topics present in large text corpora and the power-law distribution of the vocabulary of natural languages. The model, which we call latent IBP compound Dirichlet allocation (LIDA), allows for power-law distributions, both, in the number of topics summarising the documents and in the number of words defining each topic. It can be interpreted as a sparse variant of the hierarchical Pitman-Yor process when applied to topic modelling. We derive an efficient and simple collapsed Gibbs sampler closely related to the collapsed Gibbs sampler of latent Dirichlet allocation (LDA), making the model applicable in a wide range of domains. Our nonparametric Bayesian topic model compares favourably to the widely used hierarchical Dirichlet process and its heavy tailed version, the hierarchical Pitman-Yor process, on benchmark corpora. Experiments demonstrate that accounting for the power-distribution of real data is beneficial and that sparsity provides more interpretable results. PMID- 26353245 TI - Distance Dependent Infinite Latent Feature Models. AB - Latent feature models are widely used to decompose data into a small number of components. Bayesian nonparametric variants of these models, which use the Indian buffet process (IBP) as a prior over latent features, allow the number of features to be determined from the data. We present a generalization of the IBP, the distance dependent Indian buffet process (dd-IBP), for modeling non exchangeable data. It relies on distances defined between data points, biasing nearby data to share more features. The choice of distance measure allows for many kinds of dependencies, including temporal and spatial. Further, the original IBP is a special case of the dd-IBP. We develop the dd-IBP and theoretically characterize its feature-sharing properties. We derive a Markov chain Monte Carlo sampler for a linear Gaussian model with a dd-IBP prior and study its performance on real-world non-exchangeable data. PMID- 26353246 TI - A Bayesian Nonparametric Approach to Image Super-Resolution. AB - Super-resolution methods form high-resolution images from low-resolution images. In this paper, we develop a new Bayesian nonparametric model for super resolution. Our method uses a beta-Bernoulli process to learn a set of recurring visual patterns, called dictionary elements, from the data. Because it is nonparametric, the number of elements found is also determined from the data. We test the results on both benchmark and natural images, comparing with several other models from the research literature. We perform large-scale human evaluation experiments to assess the visual quality of the results. In a first implementation, we use Gibbs sampling to approximate the posterior. However, this algorithm is not feasible for large-scale data. To circumvent this, we then develop an online variational Bayes (VB) algorithm. This algorithm finds high quality dictionaries in a fraction of the time needed by the Gibbs sampler. PMID- 26353247 TI - A Survey of Non-Exchangeable Priors for Bayesian Nonparametric Models. AB - Dependent nonparametric processes extend distributions over measures, such as the Dirichlet process and the beta process, to give distributions over collections of measures, typically indexed by values in some covariate space. Such models are appropriate priors when exchangeability assumptions do not hold, and instead we want our model to vary fluidly with some set of covariates. Since the concept of dependent nonparametric processes was formalized by MacEachern, there have been a number of models proposed and used in the statistics and machine learning literatures. Many of these models exhibit underlying similarities, an understanding of which, we hope, will help in selecting an appropriate prior, developing new models, and leveraging inference techniques. PMID- 26353248 TI - Modeling Non-Gaussian Time Series with Nonparametric Bayesian Model. AB - We present a class of Bayesian copula models whose major components are the marginal (limiting) distribution of a stationary time series and the internal dynamics of the series. We argue that these are the two features with which an analyst is typically most familiar, and hence that these are natural components with which to work. For the marginal distribution, we use a nonparametric Bayesian prior distribution along with a cdf-inverse cdf transformation to obtain large support. For the internal dynamics, we rely on the traditionally successful techniques of normal-theory time series. Coupling the two components gives us a family of (Gaussian) copula transformed autoregressive models. The models provide coherent adjustments of time scales and are compatible with many extensions, including changes in volatility of the series. We describe basic properties of the models, show their ability to recover non-Gaussian marginal distributions, and use a GARCH modification of the basic model to analyze stock index return series. The models are found to provide better fit and improved short-range and long-range predictions than Gaussian competitors. The models are extensible to a large variety of fields, including continuous time models, spatial models, models for multiple series, models driven by external covariate streams, and non stationary models. PMID- 26353249 TI - Fast Nonparametric Clustering of Structured Time-Series. AB - In this publication, we combine two Bayesian nonparametric models: the Gaussian Process (GP) and the Dirichlet Process (DP). Our innovation in the GP model is to introduce a variation on the GP prior which enables us to model structured time series data, i.e., data containing groups where we wish to model inter- and intra group variability. Our innovation in the DP model is an implementation of a new fast collapsed variational inference procedure which enables us to optimize our variational approximation significantly faster than standard VB approaches. In a biological time series application we show how our model better captures salient features of the data, leading to better consistency with existing biological classifications, while the associated inference algorithm provides a significant speed-up over EM-based variational inference. PMID- 26353250 TI - Bayesian Nonparametric Methods for Partially-Observable Reinforcement Learning. AB - Making intelligent decisions from incomplete information is critical in many applications: for example, robots must choose actions based on imperfect sensors, and speech-based interfaces must infer a user's needs from noisy microphone inputs. What makes these tasks hard is that often we do not have a natural representation with which to model the domain and use for choosing actions; we must learn about the domain's properties while simultaneously performing the task. Learning a representation also involves trade-offs between modeling the data that we have seen previously and being able to make predictions about new data. This article explores learning representations of stochastic systems using Bayesian nonparametric statistics. Bayesian nonparametric methods allow the sophistication of a representation to scale gracefully with the complexity in the data. Our main contribution is a careful empirical evaluation of how representations learned using Bayesian nonparametric methods compare to other standard learning approaches, especially in support of planning and control. We show that the Bayesian aspects of the methods result in achieving state-of-the art performance in decision making with relatively few samples, while the nonparametric aspects often result in fewer computations. These results hold across a variety of different techniques for choosing actions given a representation. PMID- 26353251 TI - Gaussian Processes for Data-Efficient Learning in Robotics and Control. AB - Autonomous learning has been a promising direction in control and robotics for more than a decade since data-driven learning allows to reduce the amount of engineering knowledge, which is otherwise required. However, autonomous reinforcement learning (RL) approaches typically require many interactions with the system to learn controllers, which is a practical limitation in real systems, such as robots, where many interactions can be impractical and time consuming. To address this problem, current learning approaches typically require task-specific knowledge in form of expert demonstrations, realistic simulators, pre-shaped policies, or specific knowledge about the underlying dynamics. In this paper, we follow a different approach and speed up learning by extracting more information from data. In particular, we learn a probabilistic, non-parametric Gaussian process transition model of the system. By explicitly incorporating model uncertainty into long-term planning and controller learning our approach reduces the effects of model errors, a key problem in model-based learning. Compared to state-of-the art RL our model-based policy search method achieves an unprecedented speed of learning. We demonstrate its applicability to autonomous learning in real robot and control tasks. PMID- 26353252 TI - Scaling Multidimensional Inference for Structured Gaussian Processes. AB - Exact Gaussian process (GP) regression has O(N(3)) runtime for data size N, making it intractable for large N . Many algorithms for improving GP scaling approximate the covariance with lower rank matrices. Other work has exploited structure inherent in particular covariance functions, including GPs with implied Markov structure, and inputs on a lattice (both enable O(N) or O(N log N) runtime). However, these GP advances have not been well extended to the multidimensional input setting, despite the preponderance of multidimensional applications. This paper introduces and tests three novel extensions of structured GPs to multidimensional inputs, for models with additive and multiplicative kernels. First we present a new method for inference in additive GPs, showing a novel connection between the classic backfitting method and the Bayesian framework. We extend this model using two advances: a variant of projection pursuit regression, and a Laplace approximation for non-Gaussian observations. Lastly, for multiplicative kernel structure, we present a novel method for GPs with inputs on a multidimensional grid. We illustrate the power of these three advances on several data sets, achieving performance equal to or very close to the naive GP at orders of magnitude less cost. PMID- 26353253 TI - Bayesian Models of Graphs, Arrays and Other Exchangeable Random Structures. AB - The natural habitat of most Bayesian methods is data represented by exchangeable sequences of observations, for which de Finetti's theorem provides the theoretical foundation. Dirichlet process clustering, Gaussian process regression, and many other parametric and nonparametric Bayesian models fall within the remit of this framework; many problems arising in modern data analysis do not. This article provides an introduction to Bayesian models of graphs, matrices, and other data that can be modeled by random structures. We describe results in probability theory that generalize de Finetti's theorem to such data and discuss their relevance to nonparametric Bayesian modeling. With the basic ideas in place, we survey example models available in the literature; applications of such models include collaborative filtering, link prediction, and graph and network analysis. We also highlight connections to recent developments in graph theory and probability, and sketch the more general mathematical foundation of Bayesian methods for other types of data beyond sequences and arrays. PMID- 26353254 TI - Relational Learning and Network Modelling Using Infinite Latent Attribute Models. AB - Latent variable models for network data extract a summary of the relational structure underlying an observed network. The simplest possible models subdivide nodes of the network into clusters; the probability of a link between any two nodes then depends only on their cluster assignment. Currently available models can be classified by whether clusters are disjoint or are allowed to overlap. These models can explain a "flat" clustering structure. Hierarchical Bayesian models provide a natural approach to capture more complex dependencies. We propose a model in which objects are characterised by a latent feature vector. Each feature is itself partitioned into disjoint groups (subclusters), corresponding to a second layer of hierarchy. In experimental comparisons, the model achieves significantly improved predictive performance on social and biological link prediction tasks. The results indicate that models with a single layer hierarchy over-simplify real networks. PMID- 26353255 TI - Bayesian Nonparametric Models for Multiway Data Analysis. AB - Tensor decomposition is a powerful computational tool for multiway data analysis. Many popular tensor decomposition approaches-such as the Tucker decomposition and CANDECOMP/PARAFAC (CP)-amount to multi-linear factorization. They are insufficient to model (i) complex interactions between data entities, (ii) various data types (e.g., missing data and binary data), and (iii) noisy observations and outliers. To address these issues, we propose tensor-variate latent nonparametric Bayesian models for multiway data analysis. We name these models InfTucker. These new models essentially conduct Tucker decomposition in an infinite feature space. Unlike classical tensor decomposition models, our new approaches handle both continuous and binary data in a probabilistic framework. Unlike previous Bayesian models on matrices and tensors, our models are based on latent Gaussian or t processes with nonlinear covariance functions. Moreover, on network data, our models reduce to nonparametric stochastic blockmodels and can be used to discover latent groups and predict missing interactions. To learn the models efficiently from data, we develop a variational inference technique and explore properties of the Kronecker product for computational efficiency. Compared with a classical variational implementation, this technique reduces both time and space complexities by several orders of magnitude. On real multiway and network data, our new models achieved significantly higher prediction accuracy than state-of-art tensor decomposition methods and blockmodels. PMID- 26353256 TI - A Bayesian Predictive Model for Clustering Data of Mixed Discrete and Continuous Type. AB - Advantages of model-based clustering methods over heuristic alternatives have been widely demonstrated in the literature. Most model-based clustering algorithms assume that the data are either discrete or continuous, possibly allowing both types to be present in separate features. In this paper, we introduce a model-based approach for clustering feature vectors of mixed type, allowing each feature to simultaneously take on both categorical and real values. Such data may be encountered, for instance, in chemical and biological analyses, in the analysis of survey data, as well as in image analysis. Our model is formulated within a Bayesian predictive framework, where clustering solutions correspond to random partitions of the data. Using conjugate analysis, the posterior probability for each possible partition can be determined analytically, enabling the utilization of efficient computational search strategies for finding the posterior optimal partition. The derived model is illustrated using several synthetic and real datasets. PMID- 26353257 TI - A Contrario 2D Point Alignment Detection. AB - In spite of many interesting attempts, the problem of automatically finding alignments in a 2D set of points seems to be still open. The difficulty of the problem is illustrated here by very simple examples. We then propose an elaborate solution. We show that a correct alignment detection depends on not less than four interlaced criteria, namely the amount of masking in texture, the relative bilateral local density of the alignment, its internal regularity, and finally a redundancy reduction step. Extending tools of the a contrario detection theory, we show that all of these detection criteria can be naturally embedded in a single probabilistic a contrario model with a single user parameter, the number of false alarms. Our contribution to the a contrario theory is the use of sophisticated conditional events on random point sets, for which expectation we nevertheless find easy bounds. By these bounds the mathematical consistency of our detection model receives a simple proof. Our final algorithm also includes a new formulation of the exclusion principle in Gestalt theory to avoid redundant detections. Aiming at reproducibility, a source code and an online demo open to any data point set are provided. The method is carefully compared to three state of-the-art algorithms and an application to real data is discussed. Limitations of the final method are also illustrated and explained. PMID- 26353258 TI - A Statistical Analysis of IrisCode and Its Security Implications. AB - IrisCode has been used to gather iris data for 430 million people. Because of the huge impact of IrisCode, it is vital that it is completely understood. This paper first studies the relationship between bit probabilities and a mean of iris images (The mean of iris images is defined as the average of independent iris images.) and then uses the Chi-square statistic, the correlation coefficient and a resampling algorithm to detect statistical dependence between bits. The results show that the statistical dependence forms a graph with a sparse and structural adjacency matrix. A comparison of this graph with a graph whose edges are defined by the inner product of the Gabor filters that produce IrisCodes shows that partial statistical dependence is induced by the filters and propagates through the graph. Using this statistical information, the security risk associated with two patented template protection schemes that have been deployed in commercial systems for producing application-specific IrisCodes is analyzed. To retain high identification speed, they use the same key to lock all IrisCodes in a database. The belief has been that if the key is not compromised, the IrisCodes are secure. This study shows that even without the key, application-specific IrisCodes can be unlocked and that the key can be obtained through the statistical dependence detected. PMID- 26353259 TI - Convolutional Sparse Coding for Trajectory Reconstruction. AB - Trajectory basis Non-Rigid Structure from Motion (NRSfM) refers to the process of reconstructing the 3D trajectory of each point of a non-rigid object from just their 2D projected trajectories. Reconstruction relies on two factors: (i) the condition of the composed camera & trajectory basis matrix, and (ii) whether the trajectory basis has enough degrees of freedom to model the 3D point trajectory. These two factors are inherently conflicting. Employing a trajectory basis with small capacity has the positive characteristic of reducing the likelihood of an ill-conditioned system (when composed with the camera) during reconstruction. However, this has the negative characteristic of increasing the likelihood that the basis will not be able to fully model the object's "true" 3D point trajectories. In this paper we draw upon a well known result centering around the Reduced Isometry Property (RIP) condition for sparse signal reconstruction. RIP allow us to relax the requirement that the full trajectory basis composed with the camera matrix must be well conditioned. Further, we propose a strategy for learning an over-complete basis using convolutional sparse coding from naturally occurring point trajectory corpora to increase the likelihood that the RIP condition holds for a broad class of point trajectories and camera motions. Finally, we propose an l1 inspired objective for trajectory reconstruction that is able to "adaptively" select the smallest sub-matrix from an over-complete trajectory basis that balances (i) and (ii). We present more practical 3D reconstruction results compared to current state of the art in trajectory basis NRSfM. PMID- 26353260 TI - Dense Subgraph Partition of Positive Hypergraphs. AB - In this paper, we present a novel partition framework, called dense subgraph partition (DSP), to automatically, precisely and efficiently decompose a positive hypergraph into dense subgraphs. A positive hypergraph is a graph or hypergraph whose edges, except self-loops, have positive weights. We first define the concepts of core subgraph, conditional core subgraph, and disjoint partition of a conditional core subgraph, then define DSP based on them. The result of DSP is an ordered list of dense subgraphs with decreasing densities, which uncovers all underlying clusters, as well as outliers. A divide-and-conquer algorithm, called min-partition evolution, is proposed to efficiently compute the partition. DSP has many appealing properties. First, it is a nonparametric partition and it reveals all meaningful clusters in a bottom-up way. Second, it has an exact and efficient solution, called min-partition evolution algorithm. The min-partition evolution algorithm is a divide-and-conquer algorithm, thus time-efficient and memory-friendly, and suitable for parallel processing. Third, it is a unified partition framework for a broad range of graphs and hypergraphs. We also establish its relationship with the densest k-subgraph problem (DkS), an NP-hard but fundamental problem in graph theory, and prove that DSP gives precise solutions to DkS for all kin a graph-dependent set, called critical k-set. To our best knowledge, this is a strong result which has not been reported before. Moreover, as our experimental results show, for sparse graphs, especially web graphs, the size of critical k-set is close to the number of vertices in the graph. We test the proposed partition framework on various tasks, and the experimental results clearly illustrate its advantages. PMID- 26353261 TI - Detection and Rectification of Distorted Fingerprints. AB - Elastic distortion of fingerprints is one of the major causes for false non match. While this problem affects all fingerprint recognition applications, it is especially dangerous in negative recognition applications, such as watchlist and deduplication applications. In such applications, malicious users may purposely distort their fingerprints to evade identification. In this paper, we proposed novel algorithms to detect and rectify skin distortion based on a single fingerprint image. Distortion detection is viewed as a two-class classification problem, for which the registered ridge orientation map and period map of a fingerprint are used as the feature vector and a SVM classifier is trained to perform the classification task. Distortion rectification (or equivalently distortion field estimation) is viewed as a regression problem, where the input is a distorted fingerprint and the output is the distortion field. To solve this problem, a database (called reference database) of various distorted reference fingerprints and corresponding distortion fields is built in the offline stage, and then in the online stage, the nearest neighbor of the input fingerprint is found in the reference database and the corresponding distortion field is used to transform the input fingerprint into a normal one. Promising results have been obtained on three databases containing many distorted fingerprints, namely FVC2004 DB1, Tsinghua Distorted Fingerprint database, and the NIST SD27 latent fingerprint database. PMID- 26353262 TI - Global Contrast Based Salient Region Detection. AB - Automatic estimation of salient object regions across images, without any prior assumption or knowledge of the contents of the corresponding scenes, enhances many computer vision and computer graphics applications. We introduce a regional contrast based salient object detection algorithm, which simultaneously evaluates global contrast differences and spatial weighted coherence scores. The proposed algorithm is simple, efficient, naturally multi-scale, and produces full resolution, high-quality saliency maps. These saliency maps are further used to initialize a novel iterative version of GrabCut, namely SaliencyCut, for high quality unsupervised salient object segmentation. We extensively evaluated our algorithm using traditional salient object detection datasets, as well as a more challenging Internet image dataset. Our experimental results demonstrate that our algorithm consistently outperforms 15 existing salient object detection and segmentation methods, yielding higher precision and better recall rates. We also show that our algorithm can be used to efficiently extract salient object masks from Internet images, enabling effective sketch-based image retrieval (SBIR) via simple shape comparisons. Despite such noisy internet images, where the saliency regions are ambiguous, our saliency guided image retrieval achieves a superior retrieval rate compared with state-of-the-art SBIR methods, and additionally provides important target object region information. PMID- 26353263 TI - High-Speed Tracking with Kernelized Correlation Filters. AB - The core component of most modern trackers is a discriminative classifier, tasked with distinguishing between the target and the surrounding environment. To cope with natural image changes, this classifier is typically trained with translated and scaled sample patches. Such sets of samples are riddled with redundancies-any overlapping pixels are constrained to be the same. Based on this simple observation, we propose an analytic model for datasets of thousands of translated patches. By showing that the resulting data matrix is circulant, we can diagonalize it with the discrete Fourier transform, reducing both storage and computation by several orders of magnitude. Interestingly, for linear regression our formulation is equivalent to a correlation filter, used by some of the fastest competitive trackers. For kernel regression, however, we derive a new kernelized correlation filter (KCF), that unlike other kernel algorithms has the exact same complexity as its linear counterpart. Building on it, we also propose a fast multi-channel extension of linear correlation filters, via a linear kernel, which we call dual correlation filter (DCF). Both KCF and DCF outperform top-ranking trackers such as Struck or TLD on a 50 videos benchmark, despite running at hundreds of frames-per-second, and being implemented in a few lines of code (Algorithm 1). To encourage further developments, our tracking framework was made open-source. PMID- 26353264 TI - Learning Image Descriptors with Boosting. AB - We propose a novel and general framework to learn compact but highly discriminative floating-point and binary local feature descriptors. By leveraging the boosting-trick we first show how to efficiently train a compact floating point descriptor that is very robust to illumination and viewpoint changes. We then present the main contribution of this paper-a binary extension of the framework that demonstrates the real advantage of our approach and allows us to compress the descriptor even further. Each bit of the resulting binary descriptor, which we call BinBoost, is computed with a boosted binary hash function, and we show how to efficiently optimize the hash functions so that they are complementary, which is key to compactness and robustness. As we do not put any constraints on the weak learner configuration underlying each hash function, our general framework allows us to optimize the sampling patterns of recently proposed hand-crafted descriptors and significantly improve their performance. Moreover, our boosting scheme can easily adapt to new applications and generalize to other types of image data, such as faces, while providing state-of-the-art results at a fraction of the matching time and memory footprint. PMID- 26353265 TI - Minimum Cost Multi-Way Data Association for Optimizing Multitarget Tracking of Interacting Objects. AB - This paper presents a general formulation for a minimum cost data association problem which associates data features via one-to-one, m-to-one and one-to-n links with minimum total cost of the links. A motivating example is a problem of tracking multiple interacting nanoparticles imaged on video frames, where particles can aggregate into one particle or a particle can be split into multiple particles. Many existing multitarget tracking methods are capable of tracking non-interacting targets or tracking interacting targets of restricted degrees of interactions. The proposed formulation solves a multitarget tracking problem for general degrees of inter-object interactions. The formulation is in the form of a binary integer programming problem. We propose a polynomial time solution approach that can obtain a good relaxation solution of the binary integer programming, so the approach can be applied for multitarget tracking problems of a moderate size (for hundreds of targets over tens of time frames). The resulting solution is always integral and obtains a better duality gap than the simple linear relaxation solution of the corresponding problem. The proposed method was validated through applications to simulated multitarget tracking problems and a real multitarget tracking problem. PMID- 26353266 TI - Non-Rigid Graph Registration Using Active Testing Search. AB - We present a new approach for matching sets of branching curvilinear structures that form graphs embedded in R2 or R3 and may be subject to deformations. Unlike earlier methods, ours does not rely on local appearance similarity nor does require a good initial alignment. Furthermore, it can cope with non-linear deformations, topological differences, and partial graphs. To handle arbitrary non-linear deformations, we use Gaussian process regressions to represent the geometrical mapping relating the two graphs. In the absence of appearance information, we iteratively establish correspondences between points, update the mapping accordingly, and use it to estimate where to find the most likely correspondences that will be used in the next step. To make the computation tractable for large graphs, the set of new potential matches considered at each iteration is not selected at random as with many RANSAC-based algorithms. Instead, we introduce a so-called Active Testing Search strategy that performs a priority search to favor the most likely matches and speed-up the process. We demonstrate the effectiveness of our approach first on synthetic cases and then on angiography data, retinal fundus images, and microscopy image stacks acquired at very different resolutions. PMID- 26353267 TI - Skeletonization and Partitioning of Digital Images Using Discrete Morse Theory. AB - We show how discrete Morse theory provides a rigorous and unifying foundation for defining skeletons and partitions of grayscale digital images. We model a grayscale image as a cubical complex with a real-valued function defined on its vertices (the voxel values). This function is extended to a discrete gradient vector field using the algorithm presented in Robins, Wood, Sheppard TPAMI 33:1646 (2011). In the current paper we define basins (the building blocks of a partition) and segments of the skeleton using the stable and unstable sets associated with critical cells. The natural connection between Morse theory and homology allows us to prove the topological validity of these constructions; for example, that the skeleton is homotopic to the initial object. We simplify the basins and skeletons via Morse-theoretic cancellation of critical cells in the discrete gradient vector field using a strategy informed by persistent homology. Simple working Python code for our algorithms for efficient vector field traversal is included. Example data are taken from micro-CT images of porous materials, an application area where accurate topological models of pore connectivity are vital for fluid-flow modelling. PMID- 26353268 TI - Static Signature Synthesis: A Neuromotor Inspired Approach for Biometrics. AB - In this paper we propose a new method for generating synthetic handwritten signature images for biometric applications. The procedures we introduce imitate the mechanism of motor equivalence which divides human handwriting into two steps: the working out of an effector independent action plan and its execution via the corresponding neuromuscular path. The action plan is represented as a trajectory on a spatial grid. This contains both the signature text and its flourish, if there is one. The neuromuscular path is simulated by applying a kinematic Kaiser filter to the trajectory plan. The length of the filter depends on the pen speed which is generated using a scalar version of the sigma lognormal model. An ink deposition model, applied pixel by pixel to the pen trajectory, provides realistic static signature images. The lexical and morphological properties of the synthesized signatures as well as the range of the synthesis parameters have been estimated from real databases of real signatures such as the MCYT Off-line and the GPDS960GraySignature corpuses. The performance experiments show that by tuning only four parameters it is possible to generate synthetic identities with different stability and forgers with different skills. Therefore it is possible to create datasets of synthetic signatures with a performance similar to databases of real signatures. Moreover, we can customize the created dataset to produce skilled forgeries or simple forgeries which are easier to detect, depending on what the researcher needs. Perceptual evaluation gives an average confusion of 44.06 percent between real and synthetic signatures which shows the realism of the synthetic ones. The utility of the synthesized signatures is demonstrated by studying the influence of the pen type and number of users on an automatic signature verifier. PMID- 26353269 TI - Towards Contactless, Low-Cost and Accurate 3D Fingerprint Identification. AB - Human identification using fingerprint impressions has been widely studied and employed for more than 2000 years. Despite new advancements in the 3D imaging technologies, widely accepted representation of 3D fingerprint features and matching methodology is yet to emerge. This paper investigates 3D representation of widely employed 2D minutiae features by recovering and incorporating (i) minutiae height z and (ii) its 3D orientation phi information and illustrates an effective matching strategy for matching popular minutiae features extended in 3D space. One of the obstacles of the emerging 3D fingerprint identification systems to replace the conventional 2D fingerprint system lies in their bulk and high cost, which is mainly contributed from the usage of structured lighting system or multiple cameras. This paper attempts to addresses such key limitations of the current 3D fingerprint technologies bydeveloping the single camera-based 3D fingerprint identification system. We develop a generalized 3D minutiae matching model and recover extended 3D fingerprint features from the reconstructed 3D fingerprints. 2D fingerprint images acquired for the 3D fingerprint reconstruction can themselves be employed for the performance improvement and have been illustrated in the work detailed in this paper. This paper also attempts to answer one of the most fundamental questions on the availability of inherent discriminable information from 3D fingerprints. The experimental results are presented on a database of 240 clients 3D fingerprints, which is made publicly available to further research efforts in this area, and illustrate the discriminant power of 3D minutiae representation and matching to achieve performance improvement. PMID- 26353270 TI - A Unified Approach for Registration and Depth in Depth from Defocus. AB - Depth from Defocus (DFD) suggests a simple optical set-up to recover the shape of a scene through imaging with shallow depth of field. Although numerous methods have been proposed for DFD, less attention has been paid to the particular problem of alignment between the captured images. The inherent shift-variant defocus often prevents standard registration techniques from achieving the accuracy needed for successful shape reconstruction. In this paper, we address the DFD and registration problem in a unified framework, exploiting their mutual relation to reach a better solution for both cues. We draw a formal connection between registration and defocus blur, find its limitations and reveal the weakness of the standard isolated approaches of registration and depth estimation. The solution is approached by energy minimization. The efficiency of the associated numerical scheme is justified by showing its equivalence to the celebrated Newton-Raphson method and proof of convergence of the emerged linear system. The computationally intensive approach of DFD, newly combined with simultaneous registration, is handled by GPU computing. Experimental results demonstrate the high sensitivity of the recovered shapes to slight errors in registration and validate the superior performance of the suggested approach over two, separately applying registration and DFD alternatives. PMID- 26353271 TI - Associative Hierarchical Random Fields. AB - This paper makes two contributions: the first is the proposal of a new model-The associative hierarchical random field (AHRF), and a novel algorithm for its optimization; the second is the application of this model to the problem of semantic segmentation. Most methods for semantic segmentation are formulated as a labeling problem for variables that might correspond to either pixels or segments such as super-pixels. It is well known that the generation of super pixel segmentations is not unique. This has motivated many researchers to use multiple super pixel segmentations for problems such as semantic segmentation or single view reconstruction. These super-pixels have not yet been combined in a principled manner, this is a difficult problem, as they may overlap, or be nested in such a way that the segmentations form a segmentation tree. Our new hierarchical random field model allows information from all of the multiple segmentations to contribute to a global energy. MAP inference in this model can be performed efficiently using powerful graph cut based move making algorithms. Our framework generalizes much of the previous work based on pixels or segments, and the resulting labelings can be viewed both as a detailed segmentation at the pixel level, or at the other extreme, as a segment selector that pieces together a solution like a jigsaw, selecting the best segments from different segmentations as pieces. We evaluate its performance on some of the most challenging data sets for object class segmentation, and show that this ability to perform inference using multiple overlapping segmentations leads to state-of the-art results. PMID- 26353272 TI - Bi-Polynomial Modeling of Low-Frequency Reflectances. AB - We present a bi-polynomial reflectance model that can precisely represent the low frequency component of reflectance. Most existing reflectance models aim at accurately representing the complete reflectance domain for photo-realistic rendering purposes. In contrast, our bi-polynomial model is developed for the purpose of accurately solving inverse problems by effectively discarding the high frequency component while retaining nonlinear variations in the low-frequency part. The bi-polynomial reflectance model is useful for estimating reflectance and shape of an object. Experimental evaluation in comparison with other parametric reflectance models demonstrates that the proposed model achieves better performance in reflectometry and photometric stereo applications. PMID- 26353273 TI - "Clustering by Composition"-Unsupervised Discovery of Image Categories. AB - We define a "good image cluster" as one in which images can be easily composed (like a puzzle) using pieces from each other, while are difficult to compose from images outside the cluster. The larger and more statistically significant the pieces are, the stronger the affinity between the images. This gives rise to unsupervised discovery of very challenging image categories. We further show how multiple images can be composed from each other simultaneously and efficiently using a collaborative randomized search algorithm. This collaborative process exploits the "wisdom of crowds of images", to obtain a sparse yet meaningful set of image affinities, and in time which is almost linear in the size of the image collection. "Clustering-by-Composition" yields state-of-the-art results on current benchmark data sets. It further yields promising results on new challenging data sets, such as data sets with very few images (where a 'cluster model' cannot be 'learned' by current methods), and a subset of the PASCAL VOC data set (with huge variability in scale and appearance). PMID- 26353274 TI - Fast Exact Search in Hamming Space With Multi-Index Hashing. AB - There is growing interest in representing image data and feature descriptors using compact binary codes for fast near neighbor search. Although binary codes are motivated by their use as direct indices (addresses) into a hash table, codes longer than 32 bits are not being used as such, as it was thought to be ineffective. We introduce a rigorous way to build multiple hash tables on binary code substrings that enables exact k-nearest neighbor search in Hamming space. The approach is storage efficient and straight-forward to implement. Theoretical analysis shows that the algorithm exhibits sub-linear run-time behavior for uniformly distributed codes. Empirical results show dramatic speedups over a linear scan baseline for datasets of up to one billion codes of 64, 128, or 256 bits. PMID- 26353275 TI - Iris Image Classification Based on Hierarchical Visual Codebook. AB - Iris recognition as a reliable method for personal identification has been well studied with the objective to assign the class label of each iris image to a unique subject. In contrast, iris image classification aims to classify an iris image to an application specific category, e.g., iris liveness detection (classification of genuine and fake iris images), race classification (e.g., classification of iris images of Asian and non-Asian subjects), coarse-to-fine iris identification (classification of all iris images in the central database into multiple categories). This paper proposes a general framework for iris image classification based on texture analysis. A novel texture pattern representation method called Hierarchical Visual Codebook (HVC) is proposed to encode the texture primitives of iris images. The proposed HVC method is an integration of two existing Bag-of-Words models, namely Vocabulary Tree (VT), and Locality constrained Linear Coding (LLC). The HVC adopts a coarse-to-fine visual coding strategy and takes advantages of both VT and LLC for accurate and sparse representation of iris texture. Extensive experimental results demonstrate that the proposed iris image classification method achieves state-of-the-art performance for iris liveness detection, race classification, and coarse-to-fine iris identification. A comprehensive fake iris image database simulating four types of iris spoof attacks is developed as the benchmark for research of iris liveness detection. PMID- 26353276 TI - Learning With Augmented Features for Supervised and Semi-Supervised Heterogeneous Domain Adaptation. AB - In this paper, we study the heterogeneous domain adaptation (HDA) problem, in which the data from the source domain and the target domain are represented by heterogeneous features with different dimensions. By introducing two different projection matrices, we first transform the data from two domains into a common subspace such that the similarity between samples across different domains can be measured. We then propose a new feature mapping function for each domain, which augments the transformed samples with their original features and zeros. Existing supervised learning methods (e.g., SVM and SVR) can be readily employed by incorporating our newly proposed augmented feature representations for supervised HDA. As a showcase, we propose a novel method called Heterogeneous Feature Augmentation (HFA) based on SVM. We show that the proposed formulation can be equivalently derived as a standard Multiple Kernel Learning (MKL) problem, which is convex and thus the global solution can be guaranteed. To additionally utilize the unlabeled data in the target domain, we further propose the semi-supervised HFA (SHFA) which can simultaneously learn the target classifier as well as infer the labels of unlabeled target samples. Comprehensive experiments on three different applications clearly demonstrate that our SHFA and HFA outperform the existing HDA methods. PMID- 26353277 TI - Mixtures of Shifted AsymmetricLaplace Distributions. AB - A mixture of shifted asymmetric Laplace distributions is introduced and used for clustering and classification. A variant of the EM algorithm is developed for parameter estimation by exploiting the relationship with the generalized inverse Gaussian distribution. This approach is mathematically elegant and relatively computationally straightforward. Our novel mixture modelling approach is demonstrated on both simulated and real data to illustrate clustering and classification applications. In these analyses, our mixture of shifted asymmetric Laplace distributions performs favourably when compared to the popular Gaussian approach. This work, which marks an important step in the non-Gaussian model based clustering and classification direction, concludes with discussion as well as suggestions for future work. PMID- 26353278 TI - Online Learning and Sequential Anomaly Detection in Trajectories. AB - Detection of anomalous trajectories is an important problem in the surveillance domain. Various algorithms based on learning of normal trajectory patterns have been proposed for this problem. Yet, these algorithms typically suffer from one or more limitations: They are not designed for sequential analysis of incomplete trajectories or online learning based on an incrementally updated training set. Moreover, they typically involve tuning of many parameters, including ad-hoc anomaly thresholds, and may therefore suffer from overfitting and poorly calibrated alarm rates. In this article, we propose and investigate the Sequential Hausdorff Nearest-Neighbor Conformal Anomaly Detector (SHNN-CAD) for online learning and sequential anomaly detection in trajectories. This is a parameter-light algorithm that offers a well-founded approach to the calibration of the anomaly threshold. The discords algorithm, originally proposed by Keogh et al. , is another parameter-light anomaly detection algorithm that has previously been shown to have good classification performance on a wide range of time-series datasets, including trajectory data. We implement and investigate the performance of SHNN-CAD and the discords algorithm on four different labeled trajectory datasets. The results show that SHNN-CAD achieves competitive classification performance with minimum parameter tuning during unsupervised online learning and sequential anomaly detection in trajectories. PMID- 26353279 TI - On-Line Video Event Detection by Constraint Flow. AB - We present a novel approach in describing and detecting the composite video events based on scenarios, which constrain the configurations of target events by temporal-logical structures of primitive events. We propose a new scenario description method to represent composite events more fluently and efficiently, and discuss an on-line event detection algorithm based on a combinatorial optimization. For this purpose, constraint flow-a dynamic configuration of scenario constraints-is first generated automatically by our scenario parsing algorithm. Then, composite event detection is formulated by a constrained discrete optimization problem, whose objective is to find the best video interpretation with respect to the constraint flow. Although the search space for the optimization problem is prohibitively large, our on-line event detection algorithm based on constraint flow using dynamic programming reduces the search space dramatically, handles preprocessing errors effectively, and guarantees a globally optimal solution. Experimental results on natural videos demonstrate the effectiveness of our algorithm. PMID- 26353280 TI - Segmentation of Moving Objects by Long Term Video Analysis. AB - Motion is a strong cue for unsupervised object-level grouping. In this paper, we demonstrate that motion will be exploited most effectively, if it is regarded over larger time windows. Opposed to classical two-frame optical flow, point trajectories that span hundreds of frames are less susceptible to short-term variations that hinder separating different objects. As a positive side effect, the resulting groupings are temporally consistent over a whole video shot, a property that requires tedious post-processing in the vast majority of existing approaches. We suggest working with a paradigm that starts with semi-dense motion cues first and that fills up textureless areas afterwards based on color. This paper also contributes the Freiburg-Berkeley motion segmentation (FBMS) dataset, a large, heterogeneous benchmark with 59 sequences and pixel-accurate ground truth annotation of moving objects. PMID- 26353281 TI - Semi-Supervised Kernel Mean Shift Clustering. AB - Mean shift clustering is a powerful nonparametric technique that does not require prior knowledge of the number of clusters and does not constrain the shape of the clusters. However, being completely unsupervised, its performance suffers when the original distance metric fails to capture the underlying cluster structure. Despite recent advances in semi-supervised clustering methods, there has been little effort towards incorporating supervision into mean shift. We propose a semi-supervised framework for kernel mean shift clustering (SKMS) that uses only pairwise constraints to guide the clustering procedure. The points are first mapped to a high-dimensional kernel space where the constraints are imposed by a linear transformation of the mapped points. This is achieved by modifying the initial kernel matrix by minimizing a log det divergence-based objective function. We show the advantages of SKMS by evaluating its performance on various synthetic and real datasets while comparing with state-of-the-art semi-supervised clustering algorithms. PMID- 26353283 TI - Spatially-Constrained Similarity Measurefor Large-Scale Object Retrieval. AB - One fundamental problem in object retrieval with the bag-of-words model is its lack of spatial information. Although various approaches are proposed to incorporate spatial constraints into the model, most of them are either too strict or too loose so that they are only effective in limited cases. In this paper, a new spatially-constrained similarity measure (SCSM) is proposed to handle object rotation, scaling, view point change and appearance deformation. The similarity measure can be efficiently calculated by a voting-based method using inverted files. During the retrieval process, object localization in the database images can also be simultaneously achieved using SCSM without post processing. Furthermore, based on the retrieval and localization results of SCSM, we introduce a novel and robust re-ranking method with the k-nearest neighbors of the query for automatically refining the initial search results. Extensive performance evaluations on six public data sets show that SCSM significantly outperforms other spatial models including RANSAC-based spatial verification, while k-NN re-ranking outperforms most state-of-the-art approaches using query expansion. We also adapted SCSM for mobile product image search with an iterative algorithm to simultaneously extract the product instance from the mobile query image, identify the instance, and retrieve visually similar product images. Experiments on two product image search data sets show that our approach can robustly localize and extract the product in the query image, and hence drastically improve the retrieval accuracy over baseline methods. PMID- 26353282 TI - Soft Biometrics; Human Identification Using Comparative Descriptions. AB - Soft biometrics are a new form of biometric identification which use physical or behavioral traits that can be naturally described by humans. Unlike other biometric approaches, this allows identification based solely on verbal descriptions, bridging the semantic gap between biometrics and human description. To permit soft biometric identification the description must be accurate, yet conventional human descriptions comprising of absolute labels and estimations are often unreliable. A novel method of obtaining human descriptions will be introduced which utilizes comparative categorical labels to describe differences between subjects. This innovative approach has been shown to address many problems associated with absolute categorical labels-most critically, the descriptions contain more objective information and have increased discriminatory capabilities. Relative measurements of the subjects' traits can be inferred from comparative human descriptions using the Elo rating system. The resulting soft biometric signatures have been demonstrated to be robust and allow accurate recognition of subjects. Relative measurements can also be obtained from other forms of human representation. This is demonstrated using a support vector machine to determine relative measurements from gait biometric signatures allowing retrieval of subjects from video footage by using human comparisons, bridging the semantic gap. PMID- 26353284 TI - Understanding Collective Activities of People from Videos. AB - This paper presents a principled framework for analyzing collective activities at different levels of semantic granularity from videos. Our framework is capable of jointly tracking multiple individuals, recognizing activities performed by individuals in isolation (i.e., atomic activities such as walking or standing), recognizing the interactions between pairs of individuals (i.e., interaction activities) as well as understanding the activities of group of individuals (i.e., collective activities). A key property of our work is that it can coherently combine bottom-up information stemming from detections or fragments of tracks (or tracklets) with top-down evidence. Top-down evidence is provided by a newly proposed descriptor that captures the coherent behavior of groups of individuals in a spatial-temporal neighborhood of the sequence. Top-down evidence provides contextual information for establishing accurate associations between detections or tracklets across frames and, thus, for obtaining more robust tracking results. Bottom-up evidence percolates upwards so as to automatically infer collective activity labels. Experimental results on two challenging data sets demonstrate our theoretical claims and indicate that our model achieves enhances tracking results and the best collective classification results to date. PMID- 26353285 TI - GNCCP-Graduated NonConvexityand Concavity Procedure. AB - In this paper we propose the graduated nonconvexity and concavity procedure (GNCCP) as a general optimization framework to approximately solve the combinatorial optimization problems defined on the set of partial permutation matrices. GNCCP comprises two sub-procedures, graduated nonconvexity which realizes a convex relaxation and graduated concavity which realizes a concave relaxation. It is proved that GNCCP realizes exactly a type of convex-concave relaxation procedure (CCRP), but with a much simpler formulation without needing convex or concave relaxation in an explicit way. Actually, GNCCP involves only the gradient of the objective function and is therefore very easy to use in practical applications. Two typical related NP-hard problems, partial graph matching and quadratic assignment problem (QAP), are employed to demonstrate its simplicity and state-of-the-art performance. PMID- 26353286 TI - The Sum-over-Forests Density Index: Identifying Dense Regions in a Graph. AB - This work introduces a novel nonparametric density index defined on graphs, the Sum-over-Forests (SoF) density index. It is based on a clear and intuitive idea: high-density regions in a graph are characterized by the fact that they contain a large amount of low-cost trees with high outdegrees while low-density regions contain few ones. Therefore, a Boltzmann probability distribution on the countable set of forests in the graph is defined so that large (high-cost) forests occur with a low probability while short (low-cost) forests occur with a high probability. Then, the SoF density index of a node is defined as the expected outdegree of this node on the set of forests, thus providing a measure of density around that node. Following the matrix-forest theorem and a statistical physics framework, it is shown that the SoF density index can be easily computed in closed form through a simple matrix inversion. Experiments on artificial and real datasets show that the proposed index performs well on finding dense regions, for graphs of various origins. PMID- 26353287 TI - Transform-Invariant PCA: A Unified Approach to Fully Automatic FaceAlignment, Representation, and Recognition. AB - We develop a transform-invariant PCA (TIPCA) technique which aims to accurately characterize the intrinsic structures of the human face that are invariant to the in-plane transformations of the training images. Specially, TIPCA alternately aligns the image ensemble and creates the optimal eigenspace, with the objective to minimize the mean square error between the aligned images and their reconstructions. The learning from the FERET facial image ensemble of 1,196 subjects validates the mutual promotion between image alignment and eigenspace representation, which eventually leads to the optimized coding and recognition performance that surpasses the handcrafted alignment based on facial landmarks. Experimental results also suggest that state-of-the-art invariant descriptors, such as local binary pattern (LBP), histogram of oriented gradient (HOG), and Gabor energy filter (GEF), and classification methods, such as sparse representation based classification (SRC) and support vector machine (SVM), can benefit from using the TIPCA-aligned faces, instead of the manually eye-aligned faces that are widely regarded as the ground-truth alignment. Favorable accuracies against the state-of-the-art results on face coding and face recognition are reported. PMID- 26353288 TI - A Scalable and Accurate Descriptor for Dynamic Textures Using Bag of System Trees. AB - The bag-of-systems (BoS) representation is a descriptor of motion in a video, where dynamic texture (DT) codewords represent the typical motion patterns in spatio-temporal patches extracted from the video. The efficacy of the BoS descriptor depends on the richness of the codebook, which depends on the number of codewords in the codebook. However, for even modest sized codebooks, mapping videos onto the codebook results in a heavy computational load. In this paper we propose the BoS Tree, which constructs a bottom-up hierarchy of codewords that enables efficient mapping of videos to the BoS codebook. By leveraging the tree structure to efficiently index the codewords, the BoS Tree allows for fast look ups in the codebook and enables the practical use of larger, richer codebooks. We demonstrate the effectiveness of BoS Trees on classification of four video datasets, as well as on annotation of a video dataset and a music dataset. Finally, we show that, although the fast look-ups of BoS Tree result in different descriptors than BoS for the same video, the overall distance (and kernel) matrices are highly correlated resulting in similar classification performance. PMID- 26353289 TI - Deep Reconstruction Models for Image Set Classification. AB - Image set classification finds its applications in a number of real-life scenarios such as classification from surveillance videos, multi-view camera networks and personal albums. Compared with single image based classification, it offers more promises and has therefore attracted significant research attention in recent years. Unlike many existing methods which assume images of a set to lie on a certain geometric surface, this paper introduces a deep learning framework which makes no such prior assumptions and can automatically discover the underlying geometric structure. Specifically, a Template Deep Reconstruction Model (TDRM) is defined whose parameters are initialized by performing unsupervised pre-training in a layer-wise fashion using Gaussian Restricted Boltzmann Machines (GRBMs). The initialized TDRM is then separately trained for images of each class and class-specific DRMs are learnt. Based on the minimum reconstruction errors from the learnt class-specific models, three different voting strategies are devised for classification. Extensive experiments are performed to demonstrate the efficacy of the proposed framework for the tasks of face and object recognition from image sets. Experimental results show that the proposed method consistently outperforms the existing state of the art methods. PMID- 26353290 TI - Generalized Weiszfeld Algorithms for Lq Optimization. AB - In many computer vision applications, a desired model of some type is computed by minimizing a cost function based on several measurements. Typically, one may compute the model that minimizes the L2 cost, that is the sum of squares of measurement errors with respect to the model. However, the Lq solution which minimizes the sum of the qth power of errors usually gives more robust results in the presence of outliers for some values of q, for example, q = 1. The Weiszfeld algorithm is a classic algorithm for finding the geometric L1 mean of a set of points in Euclidean space. It is provably optimal and requires neither differentiation, nor line search. The Weiszfeld algorithm has also been generalized to find the L1 mean of a set of points on a Riemannian manifold of non-negative curvature. This paper shows that the Weiszfeld approach may be extended to a wide variety of problems to find an Lq mean for 1 <= q <; 2, while maintaining simplicity and provable convergence. We apply this problem to both single-rotation averaging (under which the algorithm provably finds the global Lq optimum) and multiple rotation averaging (for which no such proof exists). Experimental results of Lq optimization for rotations show the improved reliability and robustness compared to L2 optimization. PMID- 26353291 TI - Joint Individual-Group Modeling for Tracking. AB - We present a novel probabilistic framework that jointly models individuals and groups for tracking. Managing groups is challenging, primarily because of their nonlinear dynamics and complex layout which lead to repeated splitting and merging events. The proposed approach assumes a tight relation of mutual support between the modeling of individuals and groups, promoting the idea that groups are better modeled if individuals are considered and vice versa. This concept is translated in a mathematical model using a decentralized particle filtering framework which deals with a joint individual-group state space. The model factorizes the joint space into two dependent subspaces, where individuals and groups share the knowledge of the joint individual-group distribution. The assignment of people to the different groups (and thus group initialization, split and merge) is implemented by two alternative strategies: using classifiers trained beforehand on statistics of group configurations, and through online learning of a Dirichlet process mixture model, assuming that no training data is available before tracking. These strategies lead to two different methods that can be used on top of any person detector (simulated using the ground truth in our experiments). We provide convincing results on two recent challenging tracking benchmarks. PMID- 26353292 TI - Mirror Surface Reconstruction from a Single Image. AB - This paper tackles the problem of reconstructing the shape of a smooth mirror surface from a single image. In particular, we consider the case where the camera is observing the reflection of a static reference target in the unknown mirror. We first study the reconstruction problem given dense correspondences between 3D points on the reference target and image locations. In such conditions, our differential geometry analysis provides a theoretical proof that the shape of the mirror surface can be recovered if the pose of the reference target is known. We then relax our assumptions by considering the case where only sparse correspondences are available. In this scenario, we formulate reconstruction as an optimization problem, which can be solved using a nonlinear least-squares method. We demonstrate the effectiveness of our method on both synthetic and real images. We then provide a theoretical analysis of the potential degenerate cases with and without prior knowledge of the pose of the reference target. Finally we show that our theory can be similarly applied to the reconstruction of the surface of transparent object. PMID- 26353293 TI - On Bayesian Network Classifiers with Reduced Precision Parameters. AB - Bayesian network classifier (BNCs) are typically implemented on nowadays desktop computers. However, many real world applications require classifier implementation on embedded or low power systems. Aspects for this purpose have not been studied rigorously. We partly close this gap by analyzing reduced precision implementations of BNCs. In detail, we investigate the quantization of the parameters of BNCs with discrete valued nodes including the implications on the classification rate (CR). We derive worst-case and probabilistic bounds on the CR for different bit-widths. These bounds are evaluated on several benchmark datasets. Furthermore, we compare the classification performance and the robustness of BNCs with generatively and discriminatively optimized parameters, i.e. parameters optimized for high data likelihood and parameters optimized for classification, with respect to parameter quantization. Generatively optimized parameters are more robust for very low bit-widths, i.e. less classifications change because of quantization. However, classification performance is better for discriminatively optimized parameters for all but very low bit-widths. Additionally, we perform analysis for margin-optimized tree augmented network (TAN) structures which outperform generatively optimized TAN structures in terms of CR and robustness. PMID- 26353294 TI - Projection Operators and Moment Invariants to Image Blurring. AB - In this paper we introduce a new theory of blur invariants. Blur invariants are image features which preserve their values if the image is convolved by a point spread function (PSF) of a certain class. We present the invariants to convolution with an arbitrary N-fold symmetric PSF, both in Fourier and image domain. We introduce a notion of a primordial image as a canonical form of all blur-equivalent images. It is defined in spectral domain by means of projection operators. We prove that the moments of the primordial image are invariant to blur and we derive recursive formulae for their direct computation without actually constructing the primordial image. We further prove they form a complete set of invariants and show how to extent their invariance also to translation, rotation and scaling. We illustrate by simulated and real-data experiments their invariance and recognition power. Potential applications of this method are wherever one wants to recognize objects on blurred images. PMID- 26353295 TI - Query Specific Rank Fusion for Image Retrieval. AB - Recently two lines of image retrieval algorithms demonstrate excellent scalability: 1) local features indexed by a vocabulary tree, and 2) holistic features indexed by compact hashing codes. Although both of them are able to search visually similar images effectively, their retrieval precision may vary dramatically among queries. Therefore, combining these two types of methods is expected to further enhance the retrieval precision. However, the feature characteristics and the algorithmic procedures of these methods are dramatically different, which is very challenging for the feature-level fusion. This motivates us to investigate how to fuse the ordered retrieval sets, i.e., the ranks of images, given by multiple retrieval methods, to boost the retrieval precision without sacrificing their scalability. In this paper, we model retrieval ranks as graphs of candidate images and propose a graph-based query specific fusion approach, where multiple graphs are merged and reranked by conducting a link analysis on a fused graph. The retrieval quality of an individual method is measured on-the-fly by assessing the consistency of the top candidates' nearest neighborhoods. Hence, it is capable of adaptively integrating the strengths of the retrieval methods using local or holistic features for different query images. This proposed method does not need any supervision, has few parameters, and is easy to implement. Extensive and thorough experiments have been conducted on four public datasets, i.e., the UKbench, Corel-5K, Holidays and the large scale San Francisco Landmarks datasets. Our proposed method has achieved very competitive performance, including state-of-the-art results on several data sets, e.g., the N-S score 3.83 for UKbench. PMID- 26353296 TI - Single and Multiple Object Tracking Using a Multi-Feature Joint Sparse Representation. AB - In this paper, we propose a tracking algorithm based on a multi-feature joint sparse representation. The templates for the sparse representation can include pixel values, textures, and edges. In the multi-feature joint optimization, noise or occlusion is dealt with using a set of trivial templates. A sparse weight constraint is introduced to dynamically select the relevant templates from the full set of templates. A variance ratio measure is adopted to adaptively adjust the weights of different features. The multi-feature template set is updated adaptively. We further propose an algorithm for tracking multi-objects with occlusion handling based on the multi-feature joint sparse reconstruction. The observation model based on sparse reconstruction automatically focuses on the visible parts of an occluded object by using the information in the trivial templates. The multi-object tracking is simplified into a joint Bayesian inference. The experimental results show the superiority of our algorithm over several state-of-the-art tracking algorithms. PMID- 26353297 TI - Stereo Matching Using Tree Filtering. AB - Matching cost aggregation is one of the oldest and still popular methods for stereo correspondence. While effective and efficient, cost aggregation methods typically aggregate the matching cost by summing/averaging over a user-specified, local support region. This is obviously only locally-optimal, and the computational complexity of the full-kernel implementation usually depends on the region size. In this paper, the cost aggregation problem is re-examined and a non local solution is proposed. The matching cost values are aggregated adaptively based on pixel similarity on a tree structure derived from the stereo image pair to preserve depth edges. The nodes of this tree are all the image pixels, and the edges are all the edges between the nearest neighboring pixels. The similarity between any two pixels is decided by their shortest distance on the tree. The proposed method is non-local as every node receives supports from all other nodes on the tree. The proposed method can be naturally extended to the time domain for enforcing temporal coherence. Unlike previous methods, the non-local property guarantees that the depth edges will be preserved when the temporal coherency between all the video frames are considered. A non-local weighted median filter is also proposed based on the non-local cost aggregation algorithm. It has been demonstrated to outperform all local weighted median filters on disparity/depth upsampling and refinement. PMID- 26353298 TI - Stereo Reconstruction of Droplet Flight Trajectories. AB - We developed a new method for extracting 3D flight trajectories of droplets using high-speed stereo capture. We noticed that traditional multi-camera tracking techniques fare poorly on our problem, in part due to the fact that all droplets have very similar shapes, sizes and appearances. Our method uses local motion models to track individual droplets in each frame. 2D tracks are used to learn a global, non-linear motion model, which in turn can be used to estimate the 3D locations of individual droplets even when these are not visible in any camera. We have evaluated the proposed method on both synthetic and real data and our method is able to reconstruct 3D flight trajectories of hundreds of droplets. The proposed technique solves for both the 3D trajectory of a droplet and its motion model concomitantly, and we have found it to be superior to 3D reconstruction via triangulation. Furthermore, the learned global motion model allows us to relax the simultaneity assumptions of stereo camera systems. Our results suggest that, even when full stereo information is available, our unsynchronized reconstruction using the global motion model can significantly improve the 3D estimation accuracy. PMID- 26353299 TI - Unsupervised Object Class Discovery via Saliency-Guided Multiple Class Learning. AB - In this paper, we tackle the problem of common object (multiple classes) discovery from a set of input images, where we assume the presence of one object class in each image. This problem is, loosely speaking, unsupervised since we do not know a priori about the object type, location, and scale in each image. We observe that the general task of object class discovery in a fully unsupervised manner is intrinsically ambiguous; here we adopt saliency detection to propose candidate image windows/patches to turn an unsupervised learning problem into a weakly-supervised learning problem. In the paper, we propose an algorithm for simultaneously localizing objects and discovering object classes via bottom-up (saliency-guided) multiple class learning (bMCL). Our contributions are three fold: (1) we adopt saliency detection to convert unsupervised learning into multiple instance learning, formulated as bottom-up multiple class learning (bMCL); (2) we propose an integrated framework that simultaneously performs object localization, object class discovery, and object detector training; (3) we demonstrate that our framework yields significant improvements over existing methods for multi-class object discovery and possess evident advantages over competing methods in computer vision. In addition, although saliency detection has recently attracted much attention, its practical usage for high-level vision tasks has yet to be justified. Our method validates the usefulness of saliency detection to output "noisy input" for a top-down method to extract common patterns. PMID- 26353300 TI - Variational Bayesian Matrix Factorization for Bounded Support Data. AB - A novel Bayesian matrix factorization method for bounded support data is presented. Each entry in the observation matrix is assumed to be beta distributed. As the beta distribution has two parameters, two parameter matrices can be obtained, which matrices contain only nonnegative values. In order to provide low-rank matrix factorization, the nonnegative matrix factorization (NMF) technique is applied. Furthermore, each entry in the factorized matrices, i.e., the basis and excitation matrices, is assigned with gamma prior. Therefore, we name this method as beta-gamma NMF (BG-NMF). Due to the integral expression of the gamma function, estimation of the posterior distribution in the BG-NMF model can not be presented by an analytically tractable solution. With the variational inference framework and the relative convexity property of the log-inverse-beta function, we propose a new lower-bound to approximate the objective function. With this new lower-bound, we derive an analytically tractable solution to approximately calculate the posterior distributions. Each of the approximated posterior distributions is also gamma distributed, which retains the conjugacy of the Bayesian estimation. In addition, a sparse BG-NMF can be obtained by including a sparseness constraint to the gamma prior. Evaluations with synthetic data and real life data demonstrate the good performance of the proposed method. PMID- 26353301 TI - Normal Estimation of a Transparent Object Using a Video. AB - Reconstructing transparent objects is a challenging problem. While producing reasonable results for quite complex objects, existing approaches require custom calibration or somewhat expensive labor to achieve high precision. When an overall shape preserving salient and fine details is sufficient, we show in this paper a significant step toward solving the problem when the object's silhouette is available and simple user interaction is allowed, by using a video of a transparent object shot under varying illumination. Specifically, we estimate the normal map of the exterior surface of a given solid transparent object, from which the surface depth can be integrated. Our technical contribution lies in relating this normal estimation problem to one of graph-cut segmentation. Unlike conventional formulations, however, our graph is dual-layered, since we can see a transparent object's foreground as well as the background behind it. Quantitative and qualitative evaluation are performed to verify the efficacy of this practical solution. PMID- 26353302 TI - Universality of the Local Marginal Polytope. AB - We show that solving the LP relaxation of the min-sum labeling problem (also known as MAP inference problem in graphical models, discrete energy minimization, or valued constraint satisfaction) is not easier than solving any linear program. Precisely, every polytope is linear-time representable by a local marginal polytope and every LP can be reduced in linear time to a linear optimization (allowing infinite costs) over a local marginal polytope. The reduction can be done (though with a higher time complexity) even if the local marginal polytope is restricted to have a planar structure. PMID- 26353303 TI - As-Projective-As-Possible Image Stitching with Moving DLT. AB - The success of commercial image stitching tools often leads to the impression that image stitching is a "solved problem". The reality, however, is that many tools give unconvincing results when the input photos violate fairly restrictive imaging assumptions; the main two being that the photos correspond to views that differ purely by rotation, or that the imaged scene is effectively planar. Such assumptions underpin the usage of 2D projective transforms or homographies to align photos. In the hands of the casual user, such conditions are often violated, yielding misalignment artifacts or "ghosting" in the results. Accordingly, many existing image stitching tools depend critically on post processing routines to conceal ghosting. In this paper, we propose a novel estimation technique called Moving Direct Linear Transformation (Moving DLT) that is able to tweak or fine-tune the projective warp to accommodate the deviations of the input data from the idealized conditions. This produces as-projective-as possible image alignment that significantly reduces ghosting without compromising the geometric realism of perspective image stitching. Our technique thus lessens the dependency on potentially expensive postprocessing algorithms. In addition, we describe how multiple as-projective-as-possible warps can be simultaneously refined via bundle adjustment to accurately align multiple images for large panorama creation. PMID- 26353304 TI - Dynamic Probabilistic CCA for Analysis of Affective Behavior and Fusion of Continuous Annotations. AB - Fusing multiple continuous expert annotations is a crucial problem in machine learning and computer vision, particularly when dealing with uncertain and subjective tasks related to affective behavior. Inspired by the concept of inferring shared and individual latent spaces in Probabilistic Canonical Correlation Analysis (PCCA), we propose a novel, generative model that discovers temporal dependencies on the shared/individual spaces (Dynamic Probabilistic CCA, DPCCA). In order to accommodate for temporal lags, which are prominent amongst continuous annotations, we further introduce a latent warping process, leading to the DPCCA with Time Warpings (DPCTW) model. Finally, we propose two supervised variants of DPCCA/DPCTW which incorporate inputs (i.e., visual or audio features), both in a generative (SG-DPCCA) and discriminative manner (SD-DPCCA). We show that the resulting family of models (i) can be used as a unifying framework for solving the problems of temporal alignment and fusion of multiple annotations in time, (ii) can automatically rank and filter annotations based on latent posteriors or other model statistics, and (iii) that by incorporating dynamics, modeling annotation-specific biases, noise estimation, time warping and supervision, DPCTW outperforms state-of-the-art methods for both the aggregation of multiple, yet imperfect expert annotations as well as the alignment of affective behavior. PMID- 26353305 TI - Generalized Boundaries from Multiple Image Interpretations. AB - Boundary detection is a fundamental computer vision problem that is essential for a variety of tasks, such as contour and region segmentation, symmetry detection and object recognition and categorization. We propose a generalized formulation for boundary detection, with closed-form solution, applicable to the localization of different types of boundaries, such as object edges in natural images and occlusion boundaries from video. Our generalized boundary detection method (Gb) simultaneously combines low-level and mid-level image representations in a single eigenvalue problem and solves for the optimal continuous boundary orientation and strength. The closed-form solution to boundary detection enables our algorithm to achieve state-of-the-art results at a significantly lower computational cost than current methods. We also propose two complementary novel components that can seamlessly be combined with Gb: first, we introduce a soft-segmentation procedure that provides region input layers to our boundary detection algorithm for a significant improvement in accuracy, at negligible computational cost; second, we present an efficient method for contour grouping and reasoning, which when applied as a final post-processing stage, further increases the boundary detection performance. PMID- 26353306 TI - Human3.6M: Large Scale Datasets and Predictive Methods for 3D Human Sensing in Natural Environments. AB - We introduce a new dataset, Human3.6M, of 3.6 Million accurate 3D Human poses, acquired by recording the performance of 5 female and 6 male subjects, under 4 different viewpoints, for training realistic human sensing systems and for evaluating the next generation of human pose estimation models and algorithms. Besides increasing the size of the datasets in the current state-of-the-art by several orders of magnitude, we also aim to complement such datasets with a diverse set of motions and poses encountered as part of typical human activities (taking photos, talking on the phone, posing, greeting, eating, etc.), with additional synchronized image, human motion capture, and time of flight (depth) data, and with accurate 3D body scans of all the subject actors involved. We also provide controlled mixed reality evaluation scenarios where 3D human models are animated using motion capture and inserted using correct 3D geometry, in complex real environments, viewed with moving cameras, and under occlusion. Finally, we provide a set of large-scale statistical models and detailed evaluation baselines for the dataset illustrating its diversity and the scope for improvement by future work in the research community. Our experiments show that our best large scale model can leverage our full training set to obtain a 20% improvement in performance compared to a training set of the scale of the largest existing public dataset for this problem. Yet the potential for improvement by leveraging higher capacity, more complex models with our large dataset, is substantially vaster and should stimulate future research. The dataset together with code for the associated large-scale learning models, features, visualization tools, as well as the evaluation server, is available online at http://vision.imar.ro/human3.6m. PMID- 26353307 TI - Iterative Discovery of Multiple AlternativeClustering Views. AB - Complex data can be grouped and interpreted in many different ways. Most existing clustering algorithms, however, only find one clustering solution, and provide little guidance to data analysts who may not be satisfied with that single clustering and may wish to explore alternatives. We introduce a novel approach that provides several clustering solutions to the user for the purposes of exploratory data analysis. Our approach additionally captures the notion that alternative clusterings may reside in different subspaces (or views). We present an algorithm that simultaneously finds these subspaces and the corresponding clusterings. The algorithm is based on an optimization procedure that incorporates terms for cluster quality and novelty relative to previously discovered clustering solutions. We present a range of experiments that compare our approach to alternatives and explore the connections between simultaneous and iterative modes of discovery of multiple clusterings. PMID- 26353308 TI - Multiple Kernel Learning for Visual Object Recognition: A Review. AB - Multiple kernel learning (MKL) is a principled approach for selecting and combining kernels for a given recognition task. A number of studies have shown that MKL is a useful tool for object recognition, where each image is represented by multiple sets of features and MKL is applied to combine different feature sets. We review the state-of-the-art for MKL, including different formulations and algorithms for solving the related optimization problems, with the focus on their applications to object recognition. One dilemma faced by practitioners interested in using MKL for object recognition is that different studies often provide conflicting results about the effectiveness and efficiency of MKL. To resolve this, we conduct extensive experiments on standard datasets to evaluate various approaches to MKL for object recognition. We argue that the seemingly contradictory conclusions offered by studies are due to different experimental setups. The conclusions of our study are: (i) given a sufficient number of training examples and feature/kernel types, MKL is more effective for object recognition than simple kernel combination (e.g., choosing the best performing kernel or average of kernels); and (ii) among the various approaches proposed for MKL, the sequential minimal optimization, semi-infinite programming, and level method based ones are computationally most efficient. PMID- 26353309 TI - Relating Things and Stuff via ObjectProperty Interactions. AB - In the last few years, substantially different approaches have been adopted for segmenting and detecting "things" (object categories that have a well defined shape such as people and cars) and "stuff" (object categories which have an amorphous spatial extent such as grass and sky). While things have been typically detected by sliding window or Hough transform based methods, detection of stuff is generally formulated as a pixel or segment-wise classification problem. This paper proposes a framework for scene understanding that models both things and stuff using a common representation while preserving their distinct nature by using a property list. This representation allows us to enforce sophisticated geometric and semantic relationships between thing and stuff categories via property interactions in a single graphical model. We use the latest advances made in the field of discrete optimization to efficiently perform maximum a posteriori (MAP) inference in this model. We evaluate our method on the Stanford dataset by comparing it against state-of-the-art methods for object segmentation and detection. We also show that our method achieves competitive performances on the challenging PASCAL '09 segmentation dataset. PMID- 26353310 TI - Shape Analysis of Planar Multiply-Connected Objects Using Conformal Welding. AB - Shape analysis is a central problem in the field of computer vision. In 2D shape analysis, classification and recognition of objects from their observed silhouettes are extremely crucial but difficult. It usually involves an efficient representation of 2D shape space with a metric, so that its mathematical structure can be used for further analysis. Although the study of 2D simply connected shapes has been subject to a corpus of literatures, the analysis of multiply-connected shapes is comparatively less studied. In this work, we propose a representation for general 2D multiply-connected domains with arbitrary topologies using conformal welding. A metric can be defined on the proposed representation space, which gives a metric to measure dissimilarities between objects. The main idea is to map the exterior and interior of the domain conformally to unit disks and circle domains (unit disk with several inner disks removed), using holomorphic 1-forms. A set of diffeomorphisms of the unit circle S(1) can be obtained, which together with the conformal modules are used to define the shape signature. A shape distance between shape signatures can be defined to measure dissimilarities between shapes. We prove theoretically that the proposed shape signature uniquely determines the multiply-connected objects under suitable normalization. We also introduce a reconstruction algorithm to obtain shapes from their signatures. This completes our framework and allows us to move back and forth between shapes and signatures. With that, a morphing algorithm between shapes can be developed through the interpolation of the Beltrami coefficients associated with the signatures. Experiments have been carried out on shapes extracted from real images. Results demonstrate the efficacy of our proposed algorithm as a stable shape representation scheme. PMID- 26353311 TI - Stereo Time-of-Flight with Constructive Interference. AB - This paper describes a novel method to acquire depth images using a pair of ToF (Time-of-Flight) cameras. As opposed to approaches that filter, calibrate or do 3D reconstructions posterior to the image acquisition, we combine the measurements of the two cameras within a modified acquisition procedure. The new proposed stereo-ToF acquisition is composed of three stages during which we actively modify the infrared lighting of the scene: first, the two cameras emit an infrared signal one after the other (stages 1 and 2), and then, simultaneously (stage 3). Assuming the scene is static during the three stages, we gather the depth measurements obtained with both cameras and define a cost function to optimize the two depth images. A qualitative and quantitative evaluation of the performance of the proposed stereo-ToF acquisition is provided both for simulated and real ToF cameras. In both cases, the stereo-ToF acquisition produces more accurate depth measurements. Moreover, an extension to the multi-view ToF case and a detailed study on the interference specifications of the system are included. PMID- 26353312 TI - Structured Time Series Analysis for Human Action Segmentation and Recognition. AB - We address the problem of structure learning of human motion in order to recognize actions from a continuous monocular motion sequence of an arbitrary person from an arbitrary viewpoint. Human motion sequences are represented by multivariate time series in the joint-trajectories space. Under this structured time series framework, we first propose Kernelized Temporal Cut (KTC), an extension of previous works on change-point detection by incorporating Hilbert space embedding of distributions, to handle the nonparametric and high dimensionality issues of human motions. Experimental results demonstrate the effectiveness of our approach, which yields realtime segmentation, and produces high action segmentation accuracy. Second, a spatio-temporal manifold framework is proposed to model the latent structure of time series data. Then an efficient spatio-temporal alignment algorithm Dynamic Manifold Warping (DMW) is proposed for multivariate time series to calculate motion similarity between action sequences (segments). Furthermore, by combining the temporal segmentation algorithm and the alignment algorithm, online human action recognition can be performed by associating a few labeled examples from motion capture data. The results on human motion capture data and 3D depth sensor data demonstrate the effectiveness of the proposed approach in automatically segmenting and recognizing motion sequences, and its ability to handle noisy and partially occluded data, in the transfer learning module. PMID- 26353313 TI - Tracking by Sampling and IntegratingMultiple Trackers. AB - We propose the visual tracker sampler, a novel tracking algorithm that can work robustly in challenging scenarios, where several kinds of appearance and motion changes of an object can occur simultaneously. The proposed tracking algorithm accurately tracks a target by searching for appropriate trackers in each frame. Since the real-world tracking environment varies severely over time, the trackers should be adapted or newly constructed depending on the current situation, so that each specific tracker takes charge of a certain change in the object. To do this, our method obtains several samples of not only the states of the target but also the trackers themselves during the sampling process. The trackers are efficiently sampled using the Markov Chain Monte Carlo (MCMC) method from the predefined tracker space by proposing new appearance models, motion models, state representation types, and observation types, which are the important ingredients of visual trackers. All trackers are then integrated into one compound tracker through an Interacting MCMC (IMCMC) method, in which the trackers interactively communicate with one another while running in parallel. By exchanging information with others, each tracker further improves its performance, thus increasing overall tracking performance. Experimental results show that our method tracks the object accurately and reliably in realistic videos, where appearance and motion drastically change over time, and outperforms even state-of-the-art tracking methods. PMID- 26353314 TI - Visual Tracking: An Experimental Survey. AB - There is a large variety of trackers, which have been proposed in the literature during the last two decades with some mixed success. Object tracking in realistic scenarios is a difficult problem, therefore, it remains a most active area of research in computer vision. A good tracker should perform well in a large number of videos involving illumination changes, occlusion, clutter, camera motion, low contrast, specularities, and at least six more aspects. However, the performance of proposed trackers have been evaluated typically on less than ten videos, or on the special purpose datasets. In this paper, we aim to evaluate trackers systematically and experimentally on 315 video fragments covering above aspects. We selected a set of nineteen trackers to include a wide variety of algorithms often cited in literature, supplemented with trackers appearing in 2010 and 2011 for which the code was publicly available. We demonstrate that trackers can be evaluated objectively by survival curves, Kaplan Meier statistics, and Grubs testing. We find that in the evaluation practice the F-score is as effective as the object tracking accuracy (OTA) score. The analysis under a large variety of circumstances provides objective insight into the strengths and weaknesses of trackers. PMID- 26353316 TI - Learning Pullback HMM Distances. AB - Recent work in action recognition has exposed the limitations of methods which directly classify local features extracted from spatio-temporal video volumes. In opposition, encoding the actions' dynamics via generative dynamical models has a number of attractive features: however, using all-purpose distances for their classification does not necessarily deliver good results. We propose a general framework for learning distance functions for generative dynamical models, given a training set of labelled videos. The optimal distance function is selected among a family of pullback ones, induced by a parametrised automorphism of the space of models. We focus here on hidden Markov models and their model space, and design an appropriate automorphism there. Experimental results are presented which show how pullback learning greatly improves action recognition performances with respect to base distances. PMID- 26353315 TI - What Makes a Photograph Memorable? AB - When glancing at a magazine, or browsing the Internet, we are continuously exposed to photographs. Despite this overflow of visual information, humans are extremely good at remembering thousands of pictures along with some of their visual details. But not all images are equal in memory. Some stick in our minds while others are quickly forgotten. In this paper, we focus on the problem of predicting how memorable an image will be. We show that memorability is an intrinsic and stable property of an image that is shared across different viewers, and remains stable across delays. We introduce a database for which we have measured the probability that each picture will be recognized after a single view. We analyze a collection of image features, labels, and attributes that contribute to making an image memorable, and we train a predictor based on global image descriptors. We find that predicting image memorability is a task that can be addressed with current computer vision techniques. While making memorable images is a challenging task in visualization, photography, and education, this work is a first attempt to quantify this useful property of images. PMID- 26353317 TI - 3D Reasoning from Blocks to Stability. AB - Objects occupy physical space and obey physical laws. To truly understand a scene, we must reason about the space that objects in it occupy, and how each objects is supported stably by each other. In other words, we seek to understand which objects would, if moved, cause other objects to fall. This 3D volumetric reasoning is important for many scene understanding tasks, ranging from segmentation of objects to perception of a rich 3D, physically well-founded, interpretations of the scene. In this paper, we propose a new algorithm to parse a single RGB-D image with 3D block units while jointly reasoning about the segments, volumes, supporting relationships, and object stability. Our algorithm is based on the intuition that a good 3D representation of the scene is one that fits the depth data well, and is a stable, self-supporting arrangement of objects (i.e., one that does not topple). We design an energy function for representing the quality of the block representation based on these properties. Our algorithm fits 3D blocks to the depth values corresponding to image segments, and iteratively optimizes the energy function. Our proposed algorithm is the first to consider stability of objects in complex arrangements for reasoning about the underlying structure of the scene. Experimental results show that our stability reasoning framework improves RGB-D segmentation and scene volumetric representation. PMID- 26353318 TI - A New Look at Reweighted Message Passing. AB - We propose a new family of message passing techniques for MAP estimation in graphical models which we call Sequential Reweighted Message Passing (SRMP). Special cases include well-known techniques such as Min-Sum Diffusion (MSD) and a faster Sequential Tree-Reweighted Message Passing (TRW-S). Importantly, our derivation is simpler than the original derivation of TRW-S, and does not involve a decomposition into trees. This allows easy generalizations. The new family of algorithms can be viewed as a generalization of TRW-S from pairwise to higher order graphical models. We test SRMP on several real-world problems with promising results. PMID- 26353319 TI - Boundary Preserving Dense Local Regions. AB - We propose a dense local region detector to extract features suitable for image matching and object recognition tasks. Whereas traditional local interest operators rely on repeatable structures that often cross object boundaries (e.g., corners, scale-space blobs), our sampling strategy is driven by segmentation, and thus preserves object boundaries and shape. At the same time, whereas existing region-based representations are sensitive to segmentation parameters and object deformations, our novel approach to robustly sample dense sites and determine their connectivity offers better repeatability. In extensive experiments, we find that the proposed region detector provides significantly better repeatability and localization accuracy for object matching compared to an array of existing feature detectors. In addition, we show our regions lead to excellent results on two benchmark tasks that require good feature matching: weakly supervised foreground discovery and nearest neighbor-based object recognition. PMID- 26353320 TI - Context-Sensitive Dynamic Ordinal Regression for Intensity Estimation of Facial Action Units. AB - Modeling intensity of facial action units from spontaneously displayed facial expressions is challenging mainly because of high variability in subject-specific facial expressiveness, head-movements, illumination changes, etc. These factors make the target problem highly context-sensitive. However, existing methods usually ignore this context-sensitivity of the target problem. We propose a novel Conditional Ordinal Random Field (CORF) model for context-sensitive modeling of the facial action unit intensity, where the W5+ (who, when, what, where, why and how) definition of the context is used. While the proposed model is general enough to handle all six context questions, in this paper we focus on the context questions: who (the observed subject), how (the changes in facial expressions), and when (the timing of facial expressions and their intensity). The context questions who and howare modeled by means of the newly introduced context dependent covariate effects, and the context question when is modeled in terms of temporal correlation between the ordinal outputs, i.e., intensity levels of action units. We also introduce a weighted softmax-margin learning of CRFs from data with skewed distribution of the intensity levels, which is commonly encountered in spontaneous facial data. The proposed model is evaluated on intensity estimation of pain and facial action units using two recently published datasets (UNBC Shoulder Pain and DISFA) of spontaneously displayed facial expressions. Our experiments show that the proposed model performs significantly better on the target tasks compared to the state-of-the-art approaches. Furthermore, compared to traditional learning of CRFs, we show that the proposed weighted learning results in more robust parameter estimation from the imbalanced intensity data. PMID- 26353321 TI - Discriminatively Trained And-Or Graph Models for Object Shape Detection. AB - In this paper, we investigate a novel reconfigurable part-based model, namely And Or graph model, to recognize object shapes in images. Our proposed model consists of four layers: leaf-nodes at the bottom are local classifiers for detecting contour fragments; or-nodes above the leaf-nodes function as the switches to activate their child leaf-nodes, making the model reconfigurable during inference; and-nodes in a higher layer capture holistic shape deformations; one root-node on the top, which is also an or-node, activates one of its child and nodes to deal with large global variations (e.g. different poses and views). We propose a novel structural optimization algorithm to discriminatively train the And-Or model from weakly annotated data. This algorithm iteratively determines the model structures (e.g. the nodes and their layouts) along with the parameter learning. On several challenging datasets, our model demonstrates the effectiveness to perform robust shape-based object detection against background clutter and outperforms the other state-of-the-art approaches. We also release a new shape database with annotations, which includes more than 1500 challenging shape instances, for recognition and detection. PMID- 26353322 TI - Discriminative Relational Topic Models. AB - Relational topic models (RTMs) provide a probabilistic generative process to describe both the link structure and document contents for document networks, and they have shown promise on predicting network structures and discovering latent topic representations. However, existing RTMs have limitations in both the restricted model expressiveness and incapability of dealing with imbalanced network data. To expand the scope and improve the inference accuracy of RTMs, this paper presents three extensions: 1) unlike the common link likelihood with a diagonal weight matrix that allows the-same-topic interactions only, we generalize it to use a full weight matrix that captures all pairwise topic interactions and is applicable to asymmetric networks; 2) instead of doing standard Bayesian inference, we perform regularized Bayesian inference (RegBayes) with a regularization parameter to deal with the imbalanced link structure issue in real networks and improve the discriminative ability of learned latent representations; and 3) instead of doing variational approximation with strict mean-field assumptions, we present collapsed Gibbs sampling algorithms for the generalized relational topic models by exploring data augmentation without making restricting assumptions. Under the generic RegBayes framework, we carefully investigate two popular discriminative loss functions, namely, the logistic log loss and the max-margin hinge loss. Experimental results on several real network datasets demonstrate the significance of these extensions on improving prediction performance. PMID- 26353323 TI - Estimation of an Observation Satellite's Attitude Using Multimodal Pushbroom Cameras. AB - Pushbroom cameras are widely used for earth observation applications. This sensor acquires 1D images over time and uses the straight motion of the satellite to sweep out a region of space and build a 2D image. The stability of the satellite is critical during the pushbroom acquisition process. Therefore its attitude is assumed to be constant overtime. However, the recent manufacture of smaller and lighter satellites to reduce launching cost has weakened this assumption. Small oscillations of the satellite's attitude can result in noticeable warps in images, and geolocation information is lost as the satellite does not capture what it ought to. Current solutions use inertial sensors to control the attitude and correct the images, but they are costly and of limited precision. As the warped images do contain information about attitude variations, we suggest using image registration to estimate them. We exploit the geometry of the focal plane and the stationary nature of the disturbances to recover undistorted images. We embed the estimation in a Bayesian framework where image registration, a prior on attitude variations and a radiometric correction model are fused to retrieve the motion of the satellite. We illustrate the performance of our algorithm on four satellite datasets. PMID- 26353324 TI - Generalized Sparselet Models for Real-Time Multiclass Object Recognition. AB - The problem of real-time multiclass object recognition is of great practical importance in object recognition. In this paper, we describe a framework that simultaneously utilizes shared representation, reconstruction sparsity, and parallelism to enable real-time multiclass object detection with deformable part models at 5Hz on a laptop computer with almost no decrease in task performance. Our framework is trained in the standard structured output prediction formulation and is generically applicable for speeding up object recognition systems where the computational bottleneck is in multiclass, multi-convolutional inference. We experimentally demonstrate the efficiency and task performance of our method on PASCAL VOC, subset of ImageNet, Caltech101 and Caltech256 dataset. PMID- 26353325 TI - Learning Near-Optimal Cost-Sensitive Decision Policy for Object Detection. AB - Many popular object detectors, such as AdaBoost, SVM and deformable part-based models (DPM), compute additive scoring functions at a large number of windows in an image pyramid, thus computational efficiency is an important consideration in real time applications besides accuracy. In this paper, a decision policy refers to a sequence of two-sided thresholds to execute early reject and early accept based on the cumulative scores at each step. We formulate an empirical risk function as the weighted sum of the cost of computation and the loss of false alarm and missing detection. Then a policy is said to be cost-sensitive and optimal if it minimizes the risk function. While the risk function is complex due to high-order correlations among the two-sided thresholds, we find that its upper bound can be optimized by dynamic programming efficiently. We show that the upper bound is very tight empirically and thus the resulting policy is said to be near optimal. In experiments, we show that the decision policy outperforms state-of the-art cascade methods significantly, in several popular detection tasks and benchmarks, in terms of computational efficiency with similar accuracy of detection. PMID- 26353326 TI - Retrieving Similar Styles to Parse Clothing. AB - Clothing recognition is a societally and commercially important yet extremely challenging problem due to large variations in clothing appearance, layering, style, and body shape and pose. In this paper, we tackle the clothing parsing problem using a retrieval-based approach. For a query image, we find similar styles from a large database of tagged fashion images and use these examples to recognize clothing items in the query. Our approach combines parsing from: pre trained global clothing models, local clothing models learned on the fly from retrieved examples, and transferred parse-masks (Paper Doll item transfer) from retrieved examples. We evaluate our approach extensively and show significant improvements over previous state-of-the-art for both localization (clothing parsing given weak supervision in the form of tags) and detection (general clothing parsing). Our experimental results also indicate that the general pose estimation problem can benefit from clothing parsing. PMID- 26353327 TI - Semi-Supervised Affinity Propagation with Soft Instance-Level Constraints. AB - Soft-constraint semi-supervised affinity propagation (SCSSAP) adds supervision to the affinity propagation (AP) clustering algorithm without strictly enforcing instance-level constraints. Constraint violations lead to an adjustment of the AP similarity matrix at every iteration of the proposed algorithm and to addition of a penalty to the objective function. This formulation is particularly advantageous in the presence of noisy labels or noisy constraints since the penalty parameter of SCSSAP can be tuned to express our confidence in instance level constraints. When the constraints are noiseless, SCSSAP outperforms unsupervised AP and performs at least as well as the previously proposed semi supervised AP and constrained expectation maximization. In the presence of label and constraint noise, SCSSAP results in a more accurate clustering than either of the aforementioned established algorithms. Finally, we present an extension of SCSSAP which incorporates metric learning in the optimization objective and can further improve the performance of clustering. PMID- 26353328 TI - Shape Tracking with Occlusions via Coarse-to-Fine Region-Based Sobolev Descent. AB - We present a method to track the shape of an object from video. The method uses a joint shape and appearance model of the object, which is propagated to match shape and radiance in subsequent frames, determining object shape. Self occlusions and dis-occlusions of the object from camera and object motion pose difficulties to joint shape and appearance models in tracking. They are unable to adapt to new shape and appearance information, leading to inaccurate shape detection. In this work, we model self-occlusions and dis-occlusions in a joint shape and appearance tracking framework. Self-occlusions and the warp to propagate the model are coupled, thus we formulate a joint optimization problem. We derive a coarse-to-fine optimization method, advantageous in tracking, that initially perturbs the model by coarse perturbations before transitioning to finer-scale perturbations seamlessly. This coarse-to-fine behavior is automatically induced by gradient descent on a novel infinite-dimensional Riemannian manifold that we introduce. The manifold consists of planar parameterized regions, and the metric that we introduce is a novel Sobolev metric. Experiments on video exhibiting occlusions/dis-occlusions, complex radiance and background show that occlusion/dis-occlusion modeling leads to superior shape accuracy. PMID- 26353329 TI - Sparse and Dense Hybrid Representation via Dictionary Decomposition for Face Recognition. AB - Sparse representation provides an effective tool for classification under the conditions that every class has sufficient representative training samples and the training data are uncorrupted. These conditions may not hold true in many practical applications. Face identification is an example where we have a large number of identities but sufficient representative and uncorrupted training images cannot be guaranteed for every identity. A violation of the two conditions leads to a poor performance of the sparse representation-based classification (SRC). This paper addresses this critic issue by analyzing the merits and limitations of SRC. A sparse- and dense-hybrid representation (SDR) framework is proposed in this paper to alleviate the problems of SRC. We further propose a procedure of supervised low-rank (SLR) dictionary decomposition to facilitate the proposed SDR framework. In addition, the problem of the corrupted training data is also alleviated by the proposed SLR dictionary decomposition. The application of the proposed SDR-SLR approach in face recognition verifies its effectiveness and advancement to the field. Extensive experiments on benchmark face databases demonstrate that it consistently outperforms the state-of-the-art sparse representation based approaches and the performance gains are significant in most cases. PMID- 26353330 TI - Statistical Optimality in Multipartite Ranking and Ordinal Regression. AB - Statistical optimality in multipartite ranking is investigated as an extension of bipartite ranking. We consider the optimality of ranking algorithms through minimization of the theoretical risk which combines pairwise ranking errors of ordinal categories with differential ranking costs. The extension shows that for a certain class of convex loss functions including exponential loss, the optimal ranking function can be represented as a ratio of weighted conditional probability of upper categories to lower categories, where the weights are given by the misranking costs. This result also bridges traditional ranking methods such as proportional odds model in statistics with various ranking algorithms in machine learning. Further, the analysis of multipartite ranking with different costs provides a new perspective on non-smooth list-wise ranking measures such as the discounted cumulative gain and preference learning. We illustrate our findings with simulation study and real data analysis. PMID- 26353331 TI - Viewpoint Invariant Human Re-Identification in Camera Networks Using Pose Priors and Subject-Discriminative Features. AB - Human re-identification across cameras with non-overlapping fields of view is one of the most important and difficult problems in video surveillance and analysis. However, current algorithms are likely to fail in real-world scenarios for several reasons. For example, surveillance cameras are typically mounted high above the ground plane, causing serious perspective changes. Also, most algorithms approach matching across images using the same descriptors, regardless of camera viewpoint or human pose. Here, we introduce a re-identification algorithm that addresses both problems. We build a model for human appearance as a function of pose, using training data gathered from a calibrated camera. We then apply this "pose prior" in online re-identification to make matching and identification more robust to viewpoint. We further integrate person-specific features learned over the course of tracking to improve the algorithm's performance. We evaluate the performance of the proposed algorithm and compare it to several state-of-the-art algorithms, demonstrating superior performance on standard benchmarking datasets as well as a challenging new airport surveillance scenario. PMID- 26353332 TI - Why Does Rebalancing Class-Unbalanced Data Improve AUC for Linear Discriminant Analysis? AB - Many established classifiers fail to identify the minority class when it is much smaller than the majority class. To tackle this problem, researchers often first rebalance the class sizes in the training dataset, through oversampling the minority class or undersampling the majority class, and then use the rebalanced data to train the classifiers. This leads to interesting empirical patterns. In particular, using the rebalanced training data can often improve the area under the receiver operating characteristic curve (AUC) for the original, unbalanced test data. The AUC is a widely-used quantitative measure of classification performance, but the property that it increases with rebalancing has, as yet, no theoretical explanation. In this note, using Gaussian-based linear discriminant analysis (LDA) as the classifier, we demonstrate that, at least for LDA, there is an intrinsic, positive relationship between the rebalancing of class sizes and the improvement of AUC. We show that the largest improvement of AUC is achieved, asymptotically, when the two classes are fully rebalanced to be of equal sizes. PMID- 26353333 TI - A Two-Stage Framework for 3D Face Reconstruction from RGBD Images. AB - This paper proposes a new approach for 3D face reconstruction with RGBD images from an inexpensive commodity sensor. The challenges we face are: 1) substantial random noise and corruption are present in low-resolution depth maps; and 2) there is high degree of variability in pose and face expression. We develop a novel two-stage algorithm that effectively maps low-quality depth maps to realistic face models. Each stage is targeted toward a certain type of noise. The first stage extracts sparse errors from depth patches through the data-driven local sparse coding, while the second stage smooths noise on the boundaries between patches and reconstructs the global shape by combining local shapes using our template-based surface refinement. Our approach does not require any markers or user interaction. We perform quantitative and qualitative evaluations on both synthetic and real test sets. Experimental results show that the proposed approach is able to produce high-resolution 3D face models with high accuracy, even if inputs are of low quality, and have large variations in viewpoint and face expression. PMID- 26353334 TI - Adaptive Color Constancy Using Faces. AB - In this work we design an adaptive color constancy algorithm that, exploiting the skin regions found in faces, is able to estimate and correct the scene illumination. The algorithm automatically switches from global to spatially varying color correction on the basis of the illuminant estimations on the different faces detected in the image. An extensive comparison with both global and local color constancy algorithms is carried out to validate the effectiveness of the proposed algorithm in terms of both statistical and perceptual significance on a large heterogeneous data set of RAW images containing faces. PMID- 26353335 TI - Classification and Boosting with Multiple Collaborative Representations. AB - Recent advances have shown a great potential to explore collaborative representations of test samples in a dictionary composed of training samples from all classes in multi-class recognition including sparse representations. In this paper, we present two multi-class classification algorithms that make use of multiple collaborative representations in their formulations, and demonstrate performance gain of exploring this extra degree of freedom. We first present the Collaborative Representation Optimized Classifier (CROC), which strikes a balance between the nearest-subspace classifier, which assigns a test sample to the class that minimizes the distance between the sample and its principal projection in the selected class, and a Collaborative Representation based Classifier (CRC), which assigns a test sample to the class that minimizes the distance between the sample and its collaborative components. Several well-known classifiers become special cases of CROC under different regularization parameters. We show classification performance can be improved by optimally tuning the regularization parameter through cross validation. We then propose the Collaborative Representation based Boosting (CRBoosting) algorithm, which generalizes the CROC to incorporate multiple collaborative representations. Extensive numerical examples are provided with performance comparisons of different choices of collaborative representations, in particular when the test sample is available via compressive measurements. PMID- 26353336 TI - Fast Feature Pyramids for Object Detection. AB - Multi-resolution image features may be approximated via extrapolation from nearby scales, rather than being computed explicitly. This fundamental insight allows us to design object detection algorithms that are as accurate, and considerably faster, than the state-of-the-art. The computational bottleneck of many modern detectors is the computation of features at every scale of a finely-sampled image pyramid. Our key insight is that one may compute finely sampled feature pyramids at a fraction of the cost, without sacrificing performance: for a broad family of features we find that features computed at octave-spaced scale intervals are sufficient to approximate features on a finely-sampled pyramid. Extrapolation is inexpensive as compared to direct feature computation. As a result, our approximation yields considerable speedups with negligible loss in detection accuracy. We modify three diverse visual recognition systems to use fast feature pyramids and show results on both pedestrian detection (measured on the Caltech, INRIA, TUD-Brussels and ETH data sets) and general object detection (measured on the PASCAL VOC). The approach is general and is widely applicable to vision algorithms requiring fine-grained multi-scale analysis. Our approximation is valid for images with broad spectra (most natural images) and fails for images with narrow band-pass spectra (e.g., periodic textures). PMID- 26353337 TI - Image Geo-Localization Based on Multiple Nearest Neighbor Feature Matching Using Generalized Graphs. AB - In this paper, we present a new framework for geo-locating an image utilizing a novel multiple nearest neighbor feature matching method using Generalized Minimum Clique Graphs (GMCP). First, we extract local features (e.g., SIFT) from the query image and retrieve a number of nearest neighbors for each query feature from the reference data set. Next, we apply our GMCP-based feature matching to select a single nearest neighbor for each query feature such that all matches are globally consistent. Our approach to feature matching is based on the proposition that the first nearest neighbors are not necessarily the best choices for finding correspondences in image matching. Therefore, the proposed method considers multiple reference nearest neighbors as potential matches and selects the correct ones by enforcing consistency among their global features (e.g., GIST) using GMCP. In this context, we argue that using a robust distance function for finding the similarity between the global features is essential for the cases where the query matches multiple reference images with dissimilar global features. Towards this end, we propose a robust distance function based on the Gaussian Radial Basis Function (G-RBF). We evaluated the proposed framework on a new data set of 102k street view images; the experiments show it outperforms the state of the art by 10 percent. PMID- 26353338 TI - Large-Margin Multi-View Information Bottleneck. AB - In this paper, we extend the theory of the information bottleneck (IB) to learning from examples represented by multi-view features. We formulate the problem as one of encoding a communication system with multiple senders, each of which represents one view of the data. Based on the precise components filtered out from multiple information sources through a "bottleneck", a margin maximization approach is then used to strengthen the discrimination of the encoder by improving the code distance within the frame of coding theory. The resulting algorithm therefore inherits all the merits of the IB principle and coding theory. It has two distinct advantages over existing algorithms, namely, that our method finds a tradeoff between the accuracy and complexity of the multi view model, and that the encoded multi-view data retains sufficient discrimination for classification. We also derive the robustness and generalization error bound of the proposed algorithm, and reveal the specific properties of multi-view learning. First, the complementarity of multi-view features guarantees the robustness of the algorithm. Second, the consensus of multi-view features reduces the empirical Rademacher complexity of the objective function, enhances the accuracy of the solution, and improves the generalization error bound of the algorithm. The resulting objective function is solved efficiently using the alternating direction method. Experimental results on annotation, classification and recognition tasks demonstrate that the proposed algorithm is promising for practical applications. PMID- 26353339 TI - Learning Local Feature Descriptors Using Convex Optimisation. AB - The objective of this work is to learn descriptors suitable for the sparse feature detectors used in viewpoint invariant matching. We make a number of novel contributions towards this goal. First, it is shown that learning the pooling regions for the descriptor can be formulated as a convex optimisation problem selecting the regions using sparsity. Second, it is shown that descriptor dimensionality reduction can also be formulated as a convex optimisation problem, using Mahalanobis matrix nuclear norm regularisation. Both formulations are based on discriminative large margin learning constraints. As the third contribution, we evaluate the performance of the compressed descriptors, obtained from the learnt real-valued descriptors by binarisation. Finally, we propose an extension of our learning formulations to a weakly supervised case, which allows us to learn the descriptors from unannotated image collections. It is demonstrated that the new learning methods improve over the state of the art in descriptor learning on the annotated local patches data set of Brown et al. and unannotated photo collections of Philbin et al. PMID- 26353340 TI - Measuring Crowd Collectiveness. AB - Collective motions of crowds are common in nature and have attracted a great deal of attention in a variety of multidisciplinary fields. Collectiveness, which indicates the degree of individuals acting as a union, is a fundamental and universal measurement for various crowd systems. By quantifying the topological structures of collective manifolds of crowd, this paper proposes a descriptor of collectiveness and its efficient computation for the crowd and its constituent individuals. The Collective Merging algorithm is then proposed to detect collective motions from random motions. We validate the effectiveness and robustness of the proposed collectiveness on the system of self-driven particles as well as other real crowd systems such as pedestrian crowds and bacteria colony. We compare the collectiveness descriptor with human perception for collective motion and show their high consistency. As a universal descriptor, the proposed crowd collectiveness can be used to compare different crowd systems. It has a wide range of applications, such as detecting collective motions from crowd clutters, monitoring crowd dynamics, and generating maps of collectiveness for crowded scenes. A new Collective Motion Database, which consists of 413 video clips from 62 crowded scenes, is released to the public. PMID- 26353341 TI - Multiclass Data Segmentation Using Diffuse Interface Methods on Graphs. AB - We present two graph-based algorithms for multiclass segmentation of high dimensional data on graphs. The algorithms use a diffuse interface model based on the Ginzburg-Landau functional, related to total variation and graph cuts. A multiclass extension is introduced using the Gibbs simplex, with the functional's double-well potential modified to handle the multiclass case. The first algorithm minimizes the functional using a convex splitting numerical scheme. The second algorithm uses a graph adaptation of the classical numerical Merriman-Bence-Osher (MBO) scheme, which alternates between diffusion and thresholding. We demonstrate the performance of both algorithms experimentally on synthetic data, image labeling, and several benchmark data sets such as MNIST, COIL and WebKB. We also make use of fast numerical solvers for finding the eigenvectors and eigenvalues of the graph Laplacian, and take advantage of the sparsity of the matrix. Experiments indicate that the results are competitive with or better than the current state-of-the-art in multiclass graph-based segmentation algorithms for high-dimensional data. PMID- 26353342 TI - Multi-Commodity Network Flow for Tracking Multiple People. AB - In this paper, we show that tracking multiple people whose paths may intersect can be formulated as a multi-commodity network flow problem. Our proposed framework is designed to exploit image appearance cues to prevent identity switches. Our method is effective even when such cues are only available at distant time intervals. This is unlike many current approaches that depend on appearance being exploitable from frame-to-frame. Furthermore, our algorithm lends itself to a real-time implementation. We validate our approach on three publicly available datasets that contain long and complex sequences, the APIDIS basketball dataset, the ISSIA soccer dataset, and the PETS'09 pedestrian dataset. We also demonstrate its performance on a newer basketball dataset that features complete world championship basketball matches. In all cases, our approach preserves identity better than state-of-the-art tracking algorithms. PMID- 26353343 TI - Multi-Observation Blind Deconvolution with an Adaptive Sparse Prior. AB - This paper describes a robust algorithm for estimating a single latent sharp image given multiple blurry and/or noisy observations. The underlying multi-image blind deconvolution problem is solved by linking all of the observations together via a Bayesian-inspired penalty function, which couples the unknown latent image along with a separate blur kernel and noise variance associated with each observation, all of which are estimated jointly from the data. This coupled penalty function enjoys a number of desirable properties, including a mechanism whereby the relative-concavity or sparsity is adapted as a function of the intrinsic quality of each corrupted observation. In this way, higher quality observations may automatically contribute more to the final estimate than heavily degraded ones, while troublesome local minima can largely be avoided. The resulting algorithm, which requires no essential tuning parameters, can recover a sharp image from a set of observations containing potentially both blurry and noisy examples, without knowing a priori the degradation type of each observation. Experimental results on both synthetic and real-world test images clearly demonstrate the efficacy of the proposed method. PMID- 26353344 TI - Prediction of Human Activity by Discovering Temporal Sequence Patterns. AB - Early prediction of ongoing human activity has become more valuable in a large variety of time-critical applications. To build an effective representation for prediction, human activities can be characterized by a complex temporal composition of constituent simple actions and interacting objects. Different from early detection on short-duration simple actions, we propose a novel framework for long -duration complex activity prediction by discovering three key aspects of activity: Causality, Context-cue, and Predictability. The major contributions of our work include: (1) a general framework is proposed to systematically address the problem of complex activity prediction by mining temporal sequence patterns; (2) probabilistic suffix tree (PST) is introduced to model causal relationships between constituent actions, where both large and small order Markov dependencies between action units are captured; (3) the context-cue, especially interactive objects information, is modeled through sequential pattern mining (SPM), where a series of action and object co-occurrence are encoded as a complex symbolic sequence; (4) we also present a predictive accumulative function (PAF) to depict the predictability of each kind of activity. The effectiveness of our approach is evaluated on two experimental scenarios with two data sets for each: action-only prediction and context-aware prediction. Our method achieves superior performance for predicting global activity classes and local action units. PMID- 26353345 TI - The Random Cluster Model for Robust Geometric Fitting. AB - Random hypothesis generation is central to robust geometric model fitting in computer vision. The predominant technique is to randomly sample minimal subsets of the data, and hypothesize the geometric models from the selected subsets. While taking minimal subsets increases the chance of successively "hitting" inliers in a sample, hypotheses fitted on minimal subsets may be severely biased due to the influence of measurement noise, even if the minimal subsets contain purely inliers. In this paper we propose Random Cluster Models, a technique used to simulate coupled spin systems, to conduct hypothesis generation using subsets larger than minimal. We show how large clusters of data from genuine instances of the model can be efficiently harvested to produce accurate hypotheses that are less affected by the vagaries of fitting on minimal subsets. A second aspect of the problem is the optimization of the set of structures that best fit the data. We show how our novel hypothesis sampler can be integrated seamlessly with graph cuts under a simple annealing framework to optimize the fitting efficiently. Unlike previous methods that conduct hypothesis sampling and fitting optimization in two disjoint stages, our algorithm performs the two subtasks alternatingly and in a mutually reinforcing manner. Experimental results show clear improvements in overall efficiency. PMID- 26353346 TI - Automatic and Accurate Shadow Detection Using Near-Infrared Information. AB - We present a method to automatically detect shadows in a fast and accurate manner by taking advantage of the inherent sensitivity of digital camera sensors to the near-infrared (NIR) part of the spectrum. Dark objects, which confound many shadow detection algorithms, often have much higher reflectance in the NIR. We can thus build an accurate shadow candidate map based on image pixels that are dark both in the visible and NIR representations. We further refine the shadow map by incorporating ratios of the visible to the NIR image, based on the observation that commonly encountered light sources have very distinct spectra in the NIR band. The results are validated on a new database, which contains visible/NIR images for a large variety of real-world shadow creating illuminant conditions, as well as manually labeled shadow ground truth. Both quantitative and qualitative evaluations show that our method outperforms current state-of-the art shadow detection algorithms in terms of accuracy and computational efficiency. PMID- 26353347 TI - Perceptual Annotation: Measuring Human Vision to Improve Computer Vision. AB - For many problems in computer vision, human learners are considerably better than machines. Humans possess highly accurate internal recognition and learning mechanisms that are not yet understood, and they frequently have access to more extensive training data through a lifetime of unbiased experience with the visual world. We propose to use visual psychophysics to directly leverage the abilities of human subjects to build better machine learning systems. First, we use an advanced online psychometric testing platform to make new kinds of annotation data available for learning. Second, we develop a technique for harnessing these new kinds of information-"perceptual annotations"-for support vector machines. A key intuition for this approach is that while it may remain infeasible to dramatically increase the amount of data and high-quality labels available for the training of a given system, measuring the exemplar-by-exemplar difficulty and pattern of errors of human annotators can provide important information for regularizing the solution of the system at hand. A case study for the problem face detection demonstrates that this approach yields state-of-the-art results on the challenging FDDB data set. PMID- 26353348 TI - Segmentation of 3D Meshes Using p-Spectral Clustering. AB - In this paper, we propose a new approach to get the optimal segmentation of a 3D mesh as a human can perceive using the minima rule and spectral clustering. This method is fully unsupervised and provides a hierarchical segmentation via recursive cuts. We introduce a new concept of the adjacency matrix based on cognitive studies. We also introduce the use of one-spectral clustering which leads to the optimal Cheeger cut value. PMID- 26353349 TI - Stacked Sequential Scale-Space Taylor Context. AB - We analyze sequential image labeling methods that sample the posterior label field in order to gather contextual information. We propose an effective method that extracts local Taylor coefficients from the posterior at different scales. Results show that our proposal outperforms state-of-the-art methods on MSRC-21, CAMVID, eTRIMS8 and KAIST2 data sets. PMID- 26353350 TI - Waterpixels. AB - Many approaches for image segmentation rely on a first low-level segmentation step, where an image is partitioned into homogeneous regions with enforced regularity and adherence to object boundaries. Methods to generate these superpixels have gained substantial interest in the last few years, but only a few have made it into applications in practice, in particular because the requirements on the processing time are essential but are not met by most of them. Here, we propose waterpixels as a general strategy for generating superpixels which relies on the marker controlled watershed transformation. We introduce a spatially regularized gradient to achieve a tunable tradeoff between the superpixel regularity and the adherence to object boundaries. The complexity of the resulting methods is linear with respect to the number of image pixels. We quantitatively evaluate our approach on the Berkeley segmentation database and compare it against the state-of-the-art. PMID- 26353351 TI - Edges and Corners With Shearlets. AB - Shearlets are a relatively new and very effective multi-scale framework for signal analysis. Contrary to the traditional wavelets, shearlets are capable to efficiently capture the anisotropic information in multivariate problem classes. Therefore, shearlets can be seen as the valid choice for multi-scale analysis and detection of directional sensitive visual features like edges and corners. In this paper, we start by reviewing the main properties of shearlets that are important for edge and corner detection. Then, we study algorithms for multi scale edge and corner detection based on the shearlet representation. We provide an extensive experimental assessment on benchmark data sets which empirically confirms the potential of shearlets feature detection. PMID- 26353352 TI - Visual Tracking via Sparse and Local Linear Coding. AB - The state search is an important component of any object tracking algorithm. Numerous algorithms have been proposed, but stochastic sampling methods (e.g., particle filters) are arguably one of the most effective approaches. However, the discretization of the state space complicates the search for the precise object location. In this paper, we propose a novel tracking algorithm that extends the state space of particle observations from discrete to continuous. The solution is determined accurately via iterative linear coding between two convex hulls. The algorithm is modeled by an optimal function, which can be efficiently solved by either convex sparse coding or locality constrained linear coding. The algorithm is also very flexible and can be combined with many generic object representations. Thus, we first use sparse representation to achieve an efficient searching mechanism of the algorithm and demonstrate its accuracy. Next, two other object representation models, i.e., least soft-threshold squares and adaptive structural local sparse appearance, are implemented with improved accuracy to demonstrate the flexibility of our algorithm. Qualitative and quantitative experimental results demonstrate that the proposed tracking algorithm performs favorably against the state-of-the-art methods in dynamic scenes. PMID- 26353353 TI - Efficient Shape Priors for Spline-Based Snakes. AB - Parametric active contours are an attractive approach for image segmentation, thanks to their computational efficiency. They are driven by application dependent energies that reflect the prior knowledge on the object to be segmented. We propose an energy involving shape priors acting in a regularization like manner. Thereby, the shape of the snake is orthogonally projected onto the space that spans the affine transformations of a given shape prior. The formulation of the curves is continuous, which provides computational benefits when compared with landmark-based (discrete) methods. We show that this approach improves the robustness and quality of spline-based segmentation algorithms, while its computational overhead is negligible. An interactive and ready-to-use implementation of the proposed algorithm is available and was successfully tested on real data in order to segment Drosophila flies and yeast cells in microscopic images. PMID- 26353354 TI - Robust Subspace Clustering for Multi-View Data by Exploiting Correlation Consensus. AB - More often than not, a multimedia data described by multiple features, such as color and shape features, can be naturally decomposed of multi-views. Since multi views provide complementary information to each other, great endeavors have been dedicated by leveraging multiple views instead of a single view to achieve the better clustering performance. To effectively exploit data correlation consensus among multi-views, in this paper, we study subspace clustering for multi-view data while keeping individual views well encapsulated. For characterizing data correlations, we generate a similarity matrix in a way that high affinity values are assigned to data objects within the same subspace across views, while the correlations among data objects from distinct subspaces are minimized. Before generating this matrix, however, we should consider that multi-view data in practice might be corrupted by noise. The corrupted data will significantly downgrade clustering results. We first present a novel objective function coupled with an angular based regularizer. By minimizing this function, multiple sparse vectors are obtained for each data object as its multiple representations. In fact, these sparse vectors result from reaching data correlation consensus on all views. For tackling noise corruption, we present a sparsity-based approach that refines the angular-based data correlation. Using this approach, a more ideal data similarity matrix is generated for multi-view data. Spectral clustering is then applied to the similarity matrix to obtain the final subspace clustering. Extensive experiments have been conducted to validate the effectiveness of our proposed approach. PMID- 26353355 TI - Intra Predictive Depth Map Coding Using Flexible Block Partitioning. AB - A complete encoding solution for efficient intra-based depth map compression is proposed in this paper. The algorithm, denominated predictive depth coding (PDC), was specifically developed to efficiently represent the characteristics of depth maps, mostly composed by smooth areas delimited by sharp edges. At its core, PDC involves a directional intra prediction framework and a straightforward residue coding method, combined with an optimized flexible block partitioning scheme. In order to improve the algorithm in the presence of depth edges that cannot be efficiently predicted by the directional modes, a constrained depth modeling mode, based on explicit edge representation, was developed. For residue coding, a simple and low complexity approach was investigated, using constant and linear residue modeling, depending on the prediction mode. The performance of the proposed intra depth map coding approach was evaluated based on the quality of the synthesized views using the encoded depth maps and original texture views. The experimental tests based on all intra configuration demonstrated the superior rate-distortion performance of PDC, with average bitrate savings of 6%, when compared with the current state-of-the-art intra depth map coding solution present in the 3D extension of a high-efficiency video coding (3D-HEVC) standard. By using view synthesis optimization in both PDC and 3D-HEVC encoders, the average bitrate savings increase to 14.3%. This suggests that the proposed method, without using transform-based residue coding, is an efficient alternative to the current 3D-HEVC algorithm for intra depth map coding. PMID- 26353356 TI - Hierarchical Learning of Tree Classifiers for Large-Scale Plant Species Identification. AB - In this paper, a hierarchical multi-task structural learning algorithm is developed to support large-scale plant species identification, where a visual tree is constructed for organizing large numbers of plant species in a coarse-to fine fashion and determining the inter-related learning tasks automatically. For a given parent node on the visual tree, it contains a set of sibling coarse grained categories of plant species or sibling fine-grained plant species, and a multi-task structural learning algorithm is developed to train their inter related classifiers jointly for enhancing their discrimination power. The inter level relationship constraint, e.g., a plant image must first be assigned to a parent node (high-level non-leaf node) correctly if it can further be assigned to the most relevant child node (low-level non-leaf node or leaf node) on the visual tree, is formally defined and leveraged to learn more discriminative tree classifiers over the visual tree. Our experimental results have demonstrated the effectiveness of our hierarchical multi-task structural learning algorithm on training more discriminative tree classifiers for large-scale plant species identification. PMID- 26353357 TI - Adaptive Spot Detection With Optimal Scale Selection in Fluorescence Microscopy Images. AB - Accurately detecting subcellular particles in fluorescence microscopy is of primary interest for further quantitative analysis such as counting, tracking, or classification. Our primary goal is to segment vesicles likely to share nearly the same size in fluorescence microscopy images. Our method termed adaptive thresholding of Laplacian of Gaussian (LoG) images with autoselected scale (ATLAS) automatically selects the optimal scale corresponding to the most frequent spot size in the image. Four criteria are proposed and compared to determine the optimal scale in a scale-space framework. Then, the segmentation stage amounts to thresholding the LoG of the intensity image. In contrast to other methods, the threshold is locally adapted given a probability of false alarm (PFA) specified by the user for the whole set of images to be processed. The local threshold is automatically derived from the PFA value and local image statistics estimated in a window whose size is not a critical parameter. We also propose a new data set for benchmarking, consisting of six collections of one hundred images each, which exploits backgrounds extracted from real microscopy images. We have carried out an extensive comparative evaluation on several data sets with ground-truth, which demonstrates that ATLAS outperforms existing methods. ATLAS does not need any fine parameter tuning and requires very low computation time. Convincing results are also reported on real total internal reflection fluorescence microscopy images. PMID- 26353358 TI - Spectral CT Image Restoration via an Average Image-Induced Nonlocal Means Filter. AB - GOAL: Spectral computed tomography (SCT) images reconstructed by an analytical approach often suffer from a poor signal-to-noise ratio and strong streak artifacts when sufficient photon counts are not available in SCT imaging. In reducing noise-induced artifacts in SCT images, in this study, we propose an average image-induced nonlocal means (aviNLM) filter for each energy-specific image restoration. Methods: The present aviNLM algorithm exploits redundant information in the whole energy domain. Specifically, the proposed aviNLM algorithm yields the restored results by performing a nonlocal weighted average operation on the noisy energy-specific images with the nonlocal weight matrix between the target and prior images, in which the prior image is generated from all of the images reconstructed in each energy bin. Results: Qualitative and quantitative studies are conducted to evaluate the aviNLM filter by using the data of digital phantom, physical phantom, and clinical patient data acquired from the energy-resolved and -integrated detectors, respectively. Experimental results show that the present aviNLM filter can achieve promising results for SCT image restoration in terms of noise-induced artifact suppression, cross profile, and contrast-to-noise ratio and material decomposition assessment. Conclusion and Significance: The present aviNLM algorithm has useful potential for radiation dose reduction by lowering the mAs in SCT imaging, and it may be useful for some other clinical applications, such as in myocardial perfusion imaging and radiotherapy. PMID- 26353359 TI - Multistage Nonlinear Optimization to Recover Neural Activation Patterns From Evoked Compound Action Potentials of Cochlear Implant Users. AB - OBJECTIVE: Electrically evoked compound action potentials (ECAPs) have been employed as a measure of neural activation evoked by cochlear implant (CI) stimulation. A forward-masking procedure is commonly used to reduce stimulus artefacts. This method estimates the joint neural activation produced by two electrodes-one acting as probe and the other as masker; as such, the measured ECAPs depend on the activation patterns produced by both. We describe an approach -termed panoramic ECAP ("PECAP")--that allows reconstruction of the underlying neural activation pattern of individual channels from ECAP amplitudes. METHODS: The proposed approach combines two constrained nonlinear optimization stages. PECAP was validated against simulated and physiological data from CI users. The physiological data consisted of ECAPs measured from four users of Cochlear devices. For each subject, an 18 *18 ECAP amplitude matrix was measured using a forward-masking method. RESULTS: The results from computer simulations indicate that our approach can reliably estimate the underlying activation patterns from ECAP amplitudes even for instances of neural "dead regions" or cross-turn stimulation. The operating signal-to-noise ratio (SNR) for the proposed algorithm was 5 dB or higher, which matched well the SNR measured from human physiological data. Human ECAPs were fitted with our procedure to determine neural activation patterns. CONCLUSION: PECAP can be used to identify undesirable features of the neural activation pattern of individual CI users. SIGNIFICANCE: Our approach may have clinical application as an objective measure of electrode-to-neuron interface and may be used to devise ad hoc stimulation strategies. PMID- 26353360 TI - Improved Low-Rank Filtering of Magnetic Resonance Spectroscopic Imaging Data Corrupted by Noise and B0 Field Inhomogeneity. AB - GOAL: To improve the signal-to-noise ratio (SNR) of magnetic resonance spectroscopic imaging (MRSI) data. METHODS: A low-rank filtering method recently proposed for denoising MRSI data is extended by: 1) incorporating tissue boundary constraints to enable local low-rank filtering, and 2) integrating B0 field inhomogeneity correction by rank-minimization to make the low-rank model more effective. RESULTS: The proposed method was validated using both simulated and in vivo MRSI data. Its denoising performance is also compared with an upper bound based on the constrained Cramer-Rao lower bound for low-rank filtering. CONCLUSION: Low-rank filtering can effectively improve the SNR of MRSI data corrupted by both noise and B0 field inhomogeneity. SIGNIFICANCE: The proposed low-rank filtering method will enhance the practical utility of high-resolution MRSI, where SNR has been a limiting factor. PMID- 26353361 TI - A-Optimal Projection for Image Representation. AB - We consider the problem of image representation from the perspective of statistical design. Recent studies have shown that images are possibly sampled from a low dimensional manifold despite of the fact that the ambient space is usually very high dimensional. Learning low dimensional image representations is crucial for many image processing tasks such as recognition and retrieval. Most of the existing approaches for learning low dimensional representations, such as principal component analysis (PCA) and locality preserving projections (LPP), aim at discovering the geometrical or discriminant structures in the data. In this paper, we take a different perspective from statistical experimental design, and propose a novel dimensionality reduction algorithm called A-Optimal Projection (AOP). AOP is based on a linear regression model. Specifically, AOP finds the optimal basis functions so that the expected prediction error of the regression model can be minimized if the new representations are used for training the model. Experimental results suggest that the proposed approach provides a better representation and achieves higher accuracy in image retrieval. PMID- 26353362 TI - Partial Sum Minimization of Singular Values in Robust PCA: Algorithm and Applications. AB - Robust Principal Component Analysis (RPCA) via rank minimization is a powerful tool for recovering underlying low-rank structure of clean data corrupted with sparse noise/outliers. In many low-level vision problems, not only it is known that the underlying structure of clean data is low-rank, but the exact rank of clean data is also known. Yet, when applying conventional rank minimization for those problems, the objective function is formulated in a way that does not fully utilize a priori target rank information about the problems. This observation motivates us to investigate whether there is a better alternative solution when using rank minimization. In this paper, instead of minimizing the nuclear norm, we propose to minimize the partial sum of singular values, which implicitly encourages the target rank constraint. Our experimental analyses show that, when the number of samples is deficient, our approach leads to a higher success rate than conventional rank minimization, while the solutions obtained by the two approaches are almost identical when the number of samples is more than sufficient. We apply our approach to various low-level vision problems, e.g., high dynamic range imaging, motion edge detection, photometric stereo, image alignment and recovery, and show that our results outperform those obtained by the conventional nuclear norm rank minimization method. PMID- 26353363 TI - Reconstruction-Free Action Inference from Compressive Imagers. AB - Persistent surveillance from camera networks, such as at parking lots, UAVs, etc., often results in large amounts of video data, resulting in significant challenges for inference in terms of storage, communication and computation. Compressive cameras have emerged as a potential solution to deal with the data deluge issues in such applications. However, inference tasks such as action recognition require high quality features which implies reconstructing the original video data. Much work in compressive sensing (CS) theory is geared towards solving the reconstruction problem, where state-of-the-art methods are computationally intensive and provide low-quality results at high compression rates. Thus, reconstruction-free methods for inference are much desired. In this paper, we propose reconstruction-free methods for action recognition from compressive cameras at high compression ratios of 100 and above. Recognizing actions directly from CS measurements requires features which are mostly nonlinear and thus not easily applicable. This leads us to search for such properties that are preserved in compressive measurements. To this end, we propose the use of spatio-temporal smashed filters, which are compressive domain versions of pixel-domain matched filters. We conduct experiments on publicly available databases and show that one can obtain recognition rates that are comparable to the oracle method in uncompressed setup, even for high compression ratios. PMID- 26353364 TI - Globally Optimal Hand-Eye Calibration Using Branch-and-Bound. AB - This paper introduces a novel solution to the hand-eye calibration problem. It uses camera measurements directly and, at the same time, requires neither prior knowledge of the external camera calibrations nor a known calibration target. Our algorithm uses branch-and-bound approach to minimize an objective function based on the epipolar constraint. Further, it employs Linear Programming to decide the bounding step of the algorithm.Our technique is able to recover both the unknown rotation and translation simultaneously and the solution is guaranteed to be globally optimal with respect to the Linfinity-norm. PMID- 26353365 TI - A New Measure for Analyzing and Fusing Sequences of Objects. AB - This work is related to the combinatorial data analysis problem of seriation used for data visualization and exploratory analysis. Seriation re-sequences the data, so that more similar samples or objects appear closer together, whereas dissimilar ones are further apart. Despite the large number of current algorithms to realize such re-sequencing, there has not been a systematic way for analyzing the resulting sequences, comparing them, or fusing them to obtain a single unifying one. We propose a new positional proximity measure that evaluates the similarity of two arbitrary sequences based on their agreement on pairwise positional information of the sequenced objects. Furthermore, we present various statistical properties of this measure as well as its normalized version modeled as an instance of the generalized correlation coefficient. Based on this measure, we define a new procedure for consensus seriation that fuses multiple arbitrary sequences based on a quadratic assignment problem formulation and an efficient way of approximating its solution. We also derive theoretical links with other permutation distance functions and present their associated combinatorial optimization forms for consensus tasks. The utility of the proposed contributions is demonstrated through the comparison and fusion of multiple seriation algorithms we have implemented, using many real-world datasets from different application domains. PMID- 26353366 TI - Co-Labeling for Multi-View Weakly Labeled Learning. AB - It is often expensive and time consuming to collect labeled training samples in many real-world applications. To reduce human effort on annotating training samples, many machine learning techniques (e.g., semi-supervised learning (SSL), multi-instance learning (MIL), etc.) have been studied to exploit weakly labeled training samples. Meanwhile, when the training data is represented with multiple types of features, many multi-view learning methods have shown that classifiers trained on different views can help each other to better utilize the unlabeled training samples for the SSL task. In this paper, we study a new learning problem called multi-view weakly labeled learning, in which we aim to develop a unified approach to learn robust classifiers by effectively utilizing different types of weakly labeled multi-view data from a broad range of tasks including SSL, MIL and relative outlier detection (ROD). We propose an effective approach called co labeling to solve the multi-view weakly labeled learning problem. Specifically, we model the learning problem on each view as a weakly labeled learning problem, which aims to learn an optimal classifier from a set of pseudo-label vectors generated by using the classifiers trained from other views. Unlike traditional co-training approaches using a single pseudo-label vector for training each classifier, our co-labeling approach explores different strategies to utilize the predictions from different views, biases and iterations for generating the pseudo label vectors, making our approach more robust for real-world applications. Moreover, to further improve the weakly labeled learning on each view, we also exploit the inherent group structure in the pseudo-label vectors generated from different strategies, which leads to a new multi-layer multiple kernel learning problem. Promising results for text-based image retrieval on the NUS-WIDE dataset as well as news classification and text categorization on several real-world multi-view datasets clearly demonstrate that our proposed co-labeling approach achieves state-of-the-art performance for various multi-view weakly labeled learning problems including multi-view SSL, multi-view MIL and multi-view ROD. PMID- 26353367 TI - Fast Automatic Step Size Estimation for Gradient Descent Optimization of Image Registration. AB - Fast automatic image registration is an important prerequisite for image-guided clinical procedures. However, due to the large number of voxels in an image and the complexity of registration algorithms, this process is often very slow. Stochastic gradient descent is a powerful method to iteratively solve the registration problem, but relies for convergence on a proper selection of the optimization step size. This selection is difficult to perform manually, since it depends on the input data, similarity measure and transformation model. The Adaptive Stochastic Gradient Descent (ASGD) method is an automatic approach, but it comes at a high computational cost. In this paper, we propose a new computationally efficient method (fast ASGD) to automatically determine the step size for gradient descent methods, by considering the observed distribution of the voxel displacements between iterations. A relation between the step size and the expectation and variance of the observed distribution is derived. While ASGD has quadratic complexity with respect to the transformation parameters, fast ASGD only has linear complexity. Extensive validation has been performed on different datasets with different modalities, inter/intra subjects, different similarity measures and transformation models. For all experiments, we obtained similar accuracy as ASGD. Moreover, the estimation time of fast ASGD is reduced to a very small value, from 40 s to less than 1 s when the number of parameters is 105, almost 40 times faster. Depending on the registration settings, the total registration time is reduced by a factor of 2.5-7 * for the experiments in this paper. PMID- 26353368 TI - Stain Specific Standardization of Whole-Slide Histopathological Images. AB - Variations in the color and intensity of hematoxylin and eosin (H&E) stained histological slides can potentially hamper the effectiveness of quantitative image analysis. This paper presents a fully automated algorithm for standardization of whole-slide histopathological images to reduce the effect of these variations. The proposed algorithm, called whole-slide image color standardizer (WSICS), utilizes color and spatial information to classify the image pixels into different stain components. The chromatic and density distributions for each of the stain components in the hue-saturation-density color model are aligned to match the corresponding distributions from a template whole-slide image (WSI). The performance of the WSICS algorithm was evaluated on two datasets. The first originated from 125 H&E stained WSIs of lymph nodes, sampled from 3 patients, and stained in 5 different laboratories on different days of the week. The second comprised 30 H&E stained WSIs of rat liver sections. The result of qualitative and quantitative evaluations using the first dataset demonstrate that the WSICS algorithm outperforms competing methods in terms of achieving color constancy. The WSICS algorithm consistently yields the smallest standard deviation and coefficient of variation of the normalized median intensity measure. Using the second dataset, we evaluated the impact of our algorithm on the performance of an already published necrosis quantification system. The performance of this system was significantly improved by utilizing the WSICS algorithm. The results of the empirical evaluations collectively demonstrate the potential contribution of the proposed standardization algorithm to improved diagnostic accuracy and consistency in computer-aided diagnosis for histopathology data. PMID- 26353370 TI - Texture Classification Using Local Pattern Based on Vector Quantization. AB - Local binary pattern (LBP) is a simple and effective descriptor for texture classification. However, it has two main disadvantages: (1) different structural patterns sometimes have the same binary code and (2) it is sensitive to noise. In order to overcome these disadvantages, we propose a new local descriptor named local vector quantization pattern (LVQP). In LVQP, different kinds of texture images are chosen to train a local pattern codebook, where each different structural pattern is described by a unique codeword index. Contrarily to the original LBP and its many variants, LVQP does not quantize each neighborhood pixel separately to 0/1, but aims at quantizing the whole difference vector between the central pixel and its neighborhood pixels. Since LVQP deals with the structural pattern as a whole, it has a high discriminability and is less sensitive to noise. Our experimental results, achieved by using four representative texture databases of Outex, UIUC, CUReT, and Brodatz, show that the proposed LVQP method can improve classification accuracy significantly and is more robust to noise. PMID- 26353369 TI - Registration-Based Morphometry for Shape Analysis of the Bones of the Human Wrist. AB - We present a method that quantifies point-wise changes in surface morphology of the bones of the human wrist. The proposed method, referred to as Registration based Bone Morphometry (RBM), consists of two steps: an atlas selection step and an atlas warping step. The atlas for individual wrist bones was selected based on the shortest l2 distance to the ensemble of wrist bones from a database of a healthy population of subjects. The selected atlas was then warped to the corresponding bones of individuals in the population using a non-linear registration method based on regularized l2 distance minimization. The displacement field thus calculated showed local differences in bone shape that then were used for the analysis of group differences. Our results indicate that RBM has potential to provide a standardized approach to shape analysis of bones of the human wrist. We demonstrate the performance of RBM for examining group differences in wrist bone shapes based on sex and between those of the right and left wrists in healthy individuals. We also present data to show the application of RBM for tracking bone erosion status in rheumatoid arthritis. PMID- 26353371 TI - Digital Image Watermarking via Adaptive Logo Texturization. AB - Grayscale logo watermarking is a quite well-developed area of digital image watermarking which seeks to embed into the host image another smaller logo image. The key advantage of such an approach is the ability to visually analyze the extracted logo for rapid visual authentication and other visual tasks. However, logos pose new challenges for invisible watermarking applications which need to keep the watermark imperceptible within the host image while simultaneously maintaining robustness to attacks. This paper presents an algorithm for invisible grayscale logo watermarking that operates via adaptive texturization of the logo. The central idea of our approach is to recast the watermarking task into a texture similarity task. We first separate the host image into sufficiently textured and poorly textured regions. Next, for textured regions, we transform the logo into a visually similar texture via the Arnold transform and one lossless rotation; whereas for poorly textured regions, we use only a lossless rotation. The iteration for the Arnold transform and the angle of lossless rotation are determined by a model of visual texture similarity. Finally, for each region, we embed the transformed logo into that region via a standard wavelet-based embedding scheme. We employ a multistep extraction stage, in which an affine parameter estimation is first performed to compensate for possible geometrical transformations. Testing with multiple logos on a database of host images and under a variety of attacks demonstrates that the proposed algorithm yields better overall performance than competing methods. PMID- 26353373 TI - Multiphase Interface Tracking with Fast Semi-Lagrangian Contouring. AB - We propose a semi-Lagrangian method for multiphase interface tracking. In contrast to previous methods, our method maintains an explicit polygonal mesh, which is reconstructed from an unsigned distance function and an indicator function, to track the interface of arbitrary number of phases. The surface mesh is reconstructed at each step using an efficient multiphase polygonization procedure with precomputed stencils while the distance and indicator function are updated with an accurate semi-Lagrangian path tracing from the meshes of the last step. Furthermore, we provide an adaptive data structure, multiphase distance tree, to accelerate the updating of both the distance function and the indicator function. In addition, the adaptive structure also enables us to contour the distance tree accurately with simple bisection techniques. The major advantage of our method is that it can easily handle topological changes without ambiguities and preserve both the sharp features and the volume well. We will evaluate its efficiency, accuracy and robustness in the results part with several examples. PMID- 26353372 TI - In Situ Eddy Analysis in a High-Resolution Ocean Climate Model. AB - An eddy is a feature associated with a rotating body of fluid, surrounded by a ring of shearing fluid. In the ocean, eddies are 10 to 150 km in diameter, are spawned by boundary currents and baroclinic instabilities, may live for hundreds of days, and travel for hundreds of kilometers. Eddies are important in climate studies because they transport heat, salt, and nutrients through the world's oceans and are vessels of biological productivity. The study of eddies in global ocean-climate models requires large-scale, high-resolution simulations. This poses a problem for feasible (timely) eddy analysis, as ocean simulations generate massive amounts of data, causing a bottleneck for traditional analysis workflows. To enable eddy studies, we have developed an in situ workflow for the quantitative and qualitative analysis of MPAS-Ocean, a high-resolution ocean climate model, in collaboration with the ocean model research and development process. Planned eddy analysis at high spatial and temporal resolutions will not be possible with a postprocessing workflow due to various constraints, such as storage size and I/O time, but the in situ workflow enables it and scales well to ten-thousand processing elements. PMID- 26353374 TI - New Controls for Combining Images in Correspondence. AB - When interpolating images, for instance in the context of morphing, there are myriad approaches for defining correspondence maps that align structurally similar elements. However, the actual interpolation usually involves simple functions for both geometric paths and color blending. In this paper we explore new types of controls for combining two images related by a correspondence map. Our insight is to apply recent edge-aware decomposition techniques, not just to the image content but to the map itself. Our framework establishes an intuitive low-dimensional parameter space for merging the shape and color from the two source images at both low and high frequencies. A gallery-based user interface enables interactive traversal of this rich space, to either define a morph path or synthesize new hybrid images. Extrapolation of the shape parameters achieves compelling effects. Finally we demonstrate an extension of the framework to videos. PMID- 26353375 TI - Fast Coherent Particle Advection through Time-Varying Unstructured Flow Datasets. AB - Tracing the paths of collections of particles through a flow field is a key step for many flow visualization and analysis methods. When a flow field is interpolated from the nodes of an unstructured mesh, the process of advecting a particle must first find which cell in the unstructured mesh contains the particle. Since the paths of nearby particles often diverge, the parallelization of particle advection quickly leads to incoherent memory accesses of the unstructured mesh. We have developed a new block advection GPU approach that reorganizes particles into spatially coherent bundles as they follow their advection paths, which greatly improves memory coherence and thus shared-memory GPU performance. This approach works best for flows that meet the CFL criterion on unstructured meshes of uniformly sized elements, small enough to fit at least two timesteps in GPU memory. PMID- 26353376 TI - Robot-Mediated Imitation Skill Training for Children With Autism. AB - Autism spectrum disorder (ASD) impacts 1 in 68 children in the U.S., with tremendous individual and societal costs. Technology-aided intervention, more specifically robotic intervention, has gained momentum in recent years due to the inherent affinity of many children with ASD towards technology. In this paper we present a novel robot-mediated intervention system for imitation skill learning, which is considered a core deficit area for children with ASD. The Robot-mediated Imitation Skill Training Architecture (RISTA) is designed in such a manner that it can operate either completely autonomously or in coordination with a human therapist depending on the intervention need. Experimental results are presented from small user studies validating system functionality, assessing user tolerance, and documenting subject performance. Preliminary results show that this novel robotic system draws more attention from the children with ASD and teaches gestures more effectively as compared to a human therapist. While no broad generalized conclusions can be made about the effectiveness of RISTA based on our small user studies, initial results are encouraging and justify further exploration in the future. PMID- 26353377 TI - 3D Silicon Microstructures: A New Tool for Evaluating Biological Aggressiveness of Tumor Cells. AB - In this work, silicon micromachined structures (SMS), consisting of arrays of 3- MU m-thick silicon walls separated by 50- MUm-deep, 5- MU m-wide gaps, were applied to investigate the behavior of eight tumor cell lines, with different origins and biological aggressiveness, in a three-dimensional (3D) microenvironment. Several cell culture experiments were performed on 3D-SMS and cells grown on silicon were stained for fluorescence microscopy analyses. Most of the tumor cell lines recognized in the literature as highly aggressive (OVCAR-5, A375, MDA-MB-231, and RPMI-7951) exhibited a great ability to enter and colonize the narrow deep gaps of the SMS, whereas less aggressive cell lines (OVCAR-3, Capan-1, MCF7, and NCI-H2126) demonstrated less penetration capability and tended to remain on top of the SMS. Quantitative image analyses of several fluorescence microscopy fields of silicon samples were performed for automatic cell recognition and count, in order to quantify the fraction of cells inside the gaps, with respect to the total number of cells in the examined field. Our results show that higher fractions of cells in the gaps are obtained with more aggressive cell lines, thus supporting in a quantitative way the observation that the behavior of tumor cells on the 3D-SMS depends on their aggressiveness level. PMID- 26353378 TI - Complex Network Measures in Autism Spectrum Disorders. AB - Recent studies have suggested abnormal brain network organization in subjects with Autism Spectrum Disorders (ASD). Here we applied spectral clustering algorithm, diverse centrality measures (betweenness (BC), clustering (CC), eigenvector (EC), and degree (DC)), and also the network entropy (NE) to identify brain sub-systems associated with ASD. We have found that BC increases in the following ASD clusters: in the somatomotor, default-mode, cerebellar, and fronto parietal. On the other hand, CC, EC, and DC decrease in the somatomotor, default mode, and cerebellar clusters. Additionally, NE decreases in ASD in the cerebellar cluster. These findings reinforce the hypothesis of under-connectivity in ASD and suggest that the difference in the network organization is more prominent in the cerebellar system. The cerebellar cluster presents reduced NE in ASD, which relates to a more regular organization of the networks. These results might be important to improve current understanding about the etiological processes and the development of potential tools supporting diagnosis and therapeutic interventions. PMID- 26353379 TI - Multi-Objective Particle Swarm Optimization Approach for Cost-Based Feature Selection in Classification. AB - Feature selection is an important data-preprocessing technique in classification problems such as bioinformatics and signal processing. Generally, there are some situations where a user is interested in not only maximizing the classification performance but also minimizing the cost that may be associated with features. This kind of problem is called cost-based feature selection. However, most existing feature selection approaches treat this task as a single-objective optimization problem. This paper presents the first study of multi-objective particle swarm optimization (PSO) for cost-based feature selection problems. The task of this paper is to generate a Pareto front of nondominated solutions, that is, feature subsets, to meet different requirements of decision-makers in real world applications. In order to enhance the search capability of the proposed algorithm, a probability-based encoding technology and an effective hybrid operator, together with the ideas of the crowding distance, the external archive, and the Pareto domination relationship, are applied to PSO. The proposed PSO based multi-objective feature selection algorithm is compared with several multi objective feature selection algorithms on five benchmark datasets. Experimental results show that the proposed algorithm can automatically evolve a set of nondominated solutions, and it is a highly competitive feature selection method for solving cost-based feature selection problems. PMID- 26353380 TI - A New Efficient Algorithm for the All Sorting Reversals Problem with No Bad Components. AB - The problem of finding all reversals that take a permutation one step closer to a target permutation is called the all sorting reversals problem (the ASR problem). For this problem, Siepel had an O(n (3))-time algorithm. Most complications of his algorithm stem from some peculiar structures called bad components. Since bad components are very rare in both real and simulated data, it is practical to study the ASR problem with no bad components. For the ASR problem with no bad components, Swenson et al. gave an O (n(2))-time algorithm. Very recently, Swenson found that their algorithm does not always work. In this paper, a new algorithm is presented for the ASR problem with no bad components. The time complexity is O(n(2)) in the worst case and is linear in the size of input and output in practice. PMID- 26353382 TI - Adaptive Portfolio Optimization for Multiple Electricity Markets Participation. AB - The increase of distributed energy resources, mainly based on renewable sources, requires new solutions that are able to deal with this type of resources' particular characteristics (namely, the renewable energy sources intermittent nature). The smart grid concept is increasing its consensus as the most suitable solution to facilitate the small players' participation in electric power negotiations while improving energy efficiency. The opportunity for players' participation in multiple energy negotiation environments (smart grid negotiation in addition to the already implemented market types, such as day-ahead spot markets, balancing markets, intraday negotiations, bilateral contracts, forward and futures negotiations, and among other) requires players to take suitable decisions on whether to, and how to participate in each market type. This paper proposes a portfolio optimization methodology, which provides the best investment profile for a market player, considering different market opportunities. The amount of power that each supported player should negotiate in each available market type in order to maximize its profits, considers the prices that are expected to be achieved in each market, in different contexts. The price forecasts are performed using artificial neural networks, providing a specific database with the expected prices in the different market types, at each time. This database is then used as input by an evolutionary particle swarm optimization process, which originates the most advantage participation portfolio for the market player. The proposed approach is tested and validated with simulations performed in multiagent simulator of competitive electricity markets, using real electricity markets data from the Iberian operator-MIBEL. PMID- 26353381 TI - Classifying the Progression of Ductal Carcinoma from Single-Cell Sampled Data via Integer Linear Programming: A Case Study. AB - Ductal Carcinoma In Situ (DCIS) is a precursor lesion of Invasive Ductal Carcinoma (IDC) of the breast. Investigating its temporal progression could provide fundamental new insights for the development of better diagnostic tools to predict which cases of DCIS will progress to IDC. We investigate the problem of reconstructing a plausible progression from single-cell sampled data of an individual with synchronous DCIS and IDC. Specifically, by using a number of assumptions derived from the observation of cellular atypia occurring in IDC, we design a possible predictive model using integer linear programming (ILP). Computational experiments carried out on a preexisting data set of 13 patients with simultaneous DCIS and IDC show that the corresponding predicted progression models are classifiable into categories having specific evolutionary characteristics. The approach provides new insights into mechanisms of clonal progression in breast cancers and helps illustrate the power of the ILP approach for similar problems in reconstructing tumor evolution scenarios under complex sets of constraints. PMID- 26353383 TI - A Unified Approach to Adaptive Neural Control for Nonlinear Discrete-Time Systems With Nonlinear Dead-Zone Input. AB - In this paper, an effective adaptive control approach is constructed to stabilize a class of nonlinear discrete-time systems, which contain unknown functions, unknown dead-zone input, and unknown control direction. Different from linear dead zone, the dead zone, in this paper, is a kind of nonlinear dead zone. To overcome the noncausal problem, which leads to the control scheme infeasible, the systems can be transformed into a m -step-ahead predictor. Due to nonlinear dead zone appearance, the transformed predictor still contains the nonaffine function. In addition, it is assumed that the gain function of dead-zone input and the control direction are unknown. These conditions bring about the difficulties and the complicacy in the controller design. Thus, the implicit function theorem is applied to deal with nonaffine dead-zone appearance, the problem caused by the unknown control direction can be resolved through applying the discrete Nussbaum gain, and the neural networks are used to approximate the unknown function. Based on the Lyapunov theory, all the signals of the resulting closed-loop system are proved to be semiglobal uniformly ultimately bounded. Moreover, the tracking error is proved to be regulated to a small neighborhood around zero. The feasibility of the proposed approach is demonstrated by a simulation example. PMID- 26353384 TI - Learning Transferred Weights From Co-Occurrence Data for Heterogeneous Transfer Learning. AB - One of the main research problems in heterogeneous transfer learning is to determine whether a given source domain is effective in transferring knowledge to a target domain, and then to determine how much of the knowledge should be transferred from a source domain to a target domain. The main objective of this paper is to solve this problem by evaluating the relatedness among given domains through transferred weights. We propose a novel method to learn such transferred weights with the aid of co-occurrence data, which contain the same set of instances but in different feature spaces. Because instances with the same category should have similar features, our method is to compute their principal components in each feature space such that co-occurrence data can be rerepresented by these principal components. The principal component coefficients from different feature spaces for the same instance in the co-occurrence data have the same order of significance for describing the category information. By using these principal component coefficients, the Markov Chain Monte Carlo method is employed to construct a directed cyclic network where each node is a domain and each edge weight is the conditional dependence from one domain to another domain. Here, the edge weight of the network can be employed as the transferred weight from a source domain to a target domain. The weight values can be taken as a prior for setting parameters in the existing heterogeneous transfer learning methods to control the amount of knowledge transferred from a source domain to a target domain. The experimental results on synthetic and real-world data sets are reported to illustrate the effectiveness of the proposed method that can capture strong or weak relations among feature spaces, and enhance the learning performance of heterogeneous transfer learning. PMID- 26353386 TI - KIDS ARE SCIENTISTS, TOO. PMID- 26353385 TI - Cytochrome c release from rat liver mitochondria is compromised by increased saturated cardiolipin species induced by sucrose feeding. AB - Cytochrome c release from mitochondria has been described to be related to reactive oxygen species (ROS) generation. With ROS generation being increased in fatty liver from sucrose-fed (SF) rats, we hypothesized that cytochrome c release might be positively associated with H2O2 generation from SF mitochondria. Surprisingly, cytochrome c release from mitochondria of SF liver was found to be significantly lower compared with control (C) mitochondria oxidizing pyruvate/malate or succinate. Exposure of mitochondria to exogenous superoxide radical generated by the xanthine/xanthine oxidase system elicits a dose-response cytochrome c release in both control and SF mitochondria, but cytochrome c release remains lower in SF mitochondria compared with C mitochondria. Furthermore, the addition of ebselen, PEG-catalase, or catalase, a H2O2 scavenger, significantly reduces cytochrome c release from C and SF mitochondria. Our results suggest that both intra- and extramitochondrial H2O2 are involved in cytochrome c release, but the persisting difference between C and SF levels can be attributed to the differences in cardiolipin compositions. Indeed, the ratio of palmitic acid-rich cardiolipin species was found to be increased in lipid membrane from SF mitochondria compared with C mitochondria, whereas that of linoleic acid-rich cardiolipin species was found decreased. In addition, the content of tafazzin, a protein responsible for cardiolipin remodeling, was decreased in SF mitochondria. Therefore, we conclude that the changes observed in the composition of cardiolipin molecular species in SF mitochondria may be involved in cytochrome c interaction with mitochondrial inner membrane lipid and in its reduced release from SF mitochondria. PMID- 26353387 TI - [Molecular mechanism of idiopathic basal ganglia calcification]. AB - Idiopathic basal ganglia calcification (IBGC), also known as Fahr's disease, is an inheritable neurodegenerative syndrome characterized by mineral deposits in the basal ganglia and other brain regions. Patients with IBGC are often accompanied with movement disorders, cognitive impairment as well as psychiatric abnormalities. So far, no therapeutic drug has been developed for the treatment of IBGC. Recently, genetic studies have identified several genes associated with IBGC, including SLC20A2, PDGFRB, PDGFB, ISG15 and XPR1. Loss-of-function mutations in these genes have been associated with disturbance in phosphate homeostasis in brain regions, the dysfunction of blood-brain barrier as well as enhanced IFN-alpha/beta immunity. In this review, we summarize the latest research progress in the studies on molecular genetics of IBGC, and discuss the molecular mechanisms underlying the pathophysiology of mutations of different genes. PMID- 26353388 TI - [Molecular Targeting Drugs Used or the Results of Non-Small Lung cancer Was How Much Improvement. As for Future Prospects]. PMID- 26353389 TI - [I. What is the Standard Treatment of EGFR-TKIs? Did EGFR-TKIs Improve Treatment for Non-Small Cell Lung Cancer?]. PMID- 26353390 TI - [II. Development and Future Prospects of the Third-Generation EGFR-Tyrosine Kinase Inhibitor]. PMID- 26353391 TI - [III. Role of Anti-Angiogenesis Therapy for Advanced Non-Small Cell Lung Cancer - Current Status and Future Challenges]. PMID- 26353392 TI - [IV. the Current State and Prospect of Immune Checkpoint Inhibitors Targeting the Immunosuppressive T Cell]. PMID- 26353393 TI - [On the II International Conference "Contemporary Problems of Biological Evolution", 11-14 March 2014, Moscow]. PMID- 26353394 TI - [Requirements imposed on model objects in microevolutionary investigations]. AB - Extrapolation of results of investigations of a model object is justified only within the limits of a set of objects that have essential properties in common with the modal object. Which properties are essential depends on the aim of a study. Similarity of objects emerged in the process of their independent evolution does not prove similarity of ways and mechanisms of their evolution. If the objects differ in their essential properties then extrapolation of results of investigation of an object on another one is risky because it may lead to wrong decisions and, moreover, to the loss of interest to alternative hypotheses. Positions formulated above are considered with the reference to species flocks of fishes, large African Barbus in particular. PMID- 26353395 TI - [Stable morphologies and mosaicism in the macroevolution of birds (Neornithes)]. AB - Modern orders of Neornithine birds are separated by distinct morphological gaps, hampering the development of particular models. of macroevolutionary transformations. However, recent decades have witnessed the discovery and extensive study of many fossil groups of birds, which shed light on the origin of modern higher taxa. These fossils further allow analyzing the whole process of the macroevolutionary change in this group of vertebrates during the Cenozoic. Here, a brief review is presented of the "transitional" taxa with special attention to representative of the clade Galloanseres. Almost all transitional groups of fossil birds do display mosaic morphology. It is noted that many stable morphologies (characters and character complexes) persist in different groups, occurring either as primitive states, or as advanced ones. The stable recurrence of these characters is caused by the persistence of stable ontogenetic pathways. On the other hand, independent evolution of various morphologies can be explained by the modular organization of the development. The modularity in the structure of the foot is used here as an example to show a possible way of the origin of the foot in extant perching birds (Passeriformes). The mosaic morphology of the transitional taxa is seen as the only possible way to overcome the evolutionary constraint of the parallel optimization of numerous organismal systems. It is noted that in course of macroevolutionary change, no complete filling of morphological gaps occur. Transitional forms are separated by additional gaps from their ancestors and descendants. Hence, stem groups are seen as the most probable ancestors of crown taxa. It is further noted that the evolutionary formation of some higher taxa of the living birds was initiated by the evolution of advanced morphology of the feeding apparatus and skull, while change in their. postcranial morphology was delayed. PMID- 26353396 TI - [The role of hybrid zones in speciation: a case study on chromosome races of the house mouse Mus domesticus and common shrew Sorex araneus]. AB - Although diverse complexes of chromosome races are of rather rare occurrence in mammals, that does not reduce its importance to insignificant phenomenon not worthy of studying as some unique case without direct analogy. Moreover, these complexes present virtually ideal models for estimation of the impact of hybridization on the process of microevolution. The chromosome races are characterized by almost zero level of genetic differentiation and well-defined distinctions, usually induced by chromosome rearrangements only. The presented review shows the valuable contribution of the studies on Sorex araneus and Mus domesticus chromosome Robertsonian systems into our understanding of varied impacts of hybridization on the speciation process. Particularly, it promotes better understanding of such evolutionary phenomena as "reinforcement" of reproductive isolation in secondary contact zones between divergent populations, speciation without geographic separation ("divergence with gene flow"), and "zonal raciation". PMID- 26353397 TI - [Possible evolutionary mechanisms of 'culture' in animals: The hypothesis of distributed social learning]. AB - There is a plethora of works on the origin and genesis of behavioral traditions in different animal species. Nevertheless, it still remains unclear as for which factors facilitate and which factors hinder the spreading those forms of behavior that are new for a population. Here, we present an analytical review on the topic, considering also the results of studies on 'culture' in animals and analyzing contradictions that arise when attempting to clarify the ethological mechanisms of cultural succession. The hypothesis of 'distributed social learning' is formulated, meaning that for spreading of complex behavioral stereotypes in a population the presence of few carriers of consistent stereotypes is enough under the condition that the rest of animals carry incomplete genetic programmes that start up these stereotypes. Existence of 'dormant' fragments of such programmes determines an inborn predisposition of their bearer to perform a certain sequence of acts. To complete the consistent stereotype, the simplest forms of social learning ('social alleviation') turn to be enough. The hypothesis is examined at the behavioral level and supported by experimental data obtained when studying the scenarios of hunting behavior development in ants Myrmica rubra L. It makes possible to explain the spreading of behavioral models in animal communities in a simpler way than cultural succession. PMID- 26353398 TI - [On the origin of Yersinia pestis, a causative agent of the plague: A concept of population-genetic macroevolution in transitive environment]. AB - An ecological scenario is proposed for the origin of causative agent of the plague (the bacterium Yersenia pestis) from the clone of pseudotuberculous microbe of the first serotype Y. pseudotuberculosis O:1b. Disclosed are the conditions of gradual intrusion of psychrophile saprozoonosis ancestor into the blood of the primary host, Mongolian tarbagan marmot Marmota sibirica. As an inductor of speciation acted the Sartan cooling that occurred in the end of late Pleistocene under conditions of arid ultra-continental climate in Central Asia. Soil freezing down to the level of hibernating chambers in marmot burrows initiated the transition of marmot flea, Oropsylla silantiewi, larvae to optional hemophagy on the mucous coat inside the mouth cavity of sleeping marmots. In its turn, this promoted the conditions of mass traumatic intrusion of Y pseudotuberculosis into marmots bloodstream from faecal particles getting in their mouth cavity in course of building up a plug in a burrow for hibernating. In marmot populations, the selection of bacteria underwent under conditions of heterothermy with repeated changes of hibernating marmots body temperature within the range of 5-37 degrees C (torpor-euthermy). During the warm season, when pseudotuberculous microbes are totally eliminated from the bloodstream of healthy marmots with body temperature about 37 degrees C, bacteria could survive in fleas' digestive tract in the form of biofilm developing in proventriculus as a so called blockage. Final isolation between ancestral and daughter species was helped by the development of intrapopulation antagonism related with the beginning of full-scale synthesis of bacteriocin pesticin. Population-genetic processes in the "marmot-flea" system have led to a macroevolutionary event, that is, to passage of bacteria in a new ecological niche and adaptive zone that are principally different from those of the ancestor. All the present intraspecies forms of Y. pestis that appeared due to microevolution, have originated with the subspecies Y. pestis tarbagani that has formed in Central Asia during the Sartan cooling. PMID- 26353399 TI - [Caucasian cryptic species of rodents as models for studying the problem of species and speciation]. AB - The problem of species and speciation is considered using as a model the cryptic species of rodents inhabiting the Caucasus, the mountain chain with prominent altitude environmental gradient and insular pattern of mountain habitats. These circumstances open additional possibilities for the choice of species conception (biological or phylogenetic), exploration of ancestry pathways (sympatric or allopatric speciation) of model cryptic species groups, and testing the 'refuge' hypothesis. As model species, sibling-species Sicista from the group 'caucasica' (a group of unstriped birch mice) and representatives of the vole subspecies Terricola (Microtus, Arvicolinae) were used. Based on the new data on karyology, nucleotide sequences of mitochondrial gene cytb, multivariate statistical analysis of odontologic traits, and biogeography of sibling-species Sicista from the group 'caucasica' and voles from subspecies Terricola (Microtus, Arvicolinae), their evolutionary history is reconstructed and applicable species concepts are examined. For the present sibling-species Sicista from the group 'caucasica' the allopatric dispersion is typical, which agrees with the hypothesis of speciation in refuges. The sympatry of Terricola sibling-species in the Caucasus is considered as being secondary, and their phenotypic likeness--as an adaptation to similar environmental conditions. Affirmed coexistence of sibling-species Microtus (Terricola) majori and Microtus (Terricola) daghestanicus in the Caucasus (without their hybridization) supports the biological conception of species. The existence of Sicista allospecies from the group of Caucasian unstriped birch mice is best conformed to the phylogenetic conception. However, the high level of chromosomal differences between sibling species and, in particular, between extreme variants of common evolutionary line (Sicista kazbegica, Sicista kluchorica) does not contradict the biological conception of species. PMID- 26353400 TI - [Evolution of Host-Beneficial Traits in Nitrogen-Fixing Bacteria: Modeling and Construction of Systems for Interspecies Altruism]. AB - The literature and our own data on N2-fixing bacteria forming symbioses with plants and providing convenient models to study the evolution of interspecies (microsymbionts --> hosts) altruism are considered in the review. It is presented as a deeply reorganized intraspecies altruism implemented in the clonal population of rhizobia (bacteroids --> undifferentiated bacteria) under the control of kin selection induced by plant hosts. The analysis of this model suggests that it is possible to engineer practically valuable rhizobial strains in which high N2-fixing activity is combined with decreased survival outside of plants. PMID- 26353401 TI - [Preparation of Copper and Nickel from Metallurgical Waste Products with the Use of Acidophilic Chemolithotrophic Microorganisms]. AB - The study concerns the leaching of copper, nickel, and cobalt from metallurgical production slag with trivalent iron sulphates prepared in the process of oxidation of bivalent iron ions with the use of associations of acidophilic chemolithotrophic microorganisms. At the same time, copper extraction in the solution reached 91.2%, nickel reached 74.9%, and cobalt reached 90.1%. Copper was extracted by cementation, and nickel as sulphate was extracted by electrolysis. Associations of microorganisms can then completely bioregenerate the solution obtained after leaching. PMID- 26353402 TI - [Intensification of Microbial Decomposition of Organic Fraction of Municipal Waste: Laboratory and Field Experiments]. AB - Methods of intensifying the anaerobic microbial decomposition of the organic fraction of municipal solid waste (MSW) on an MSW landfill and in anaerobic reactors were studied. It was discovered that it is preferable for the initiation and stabilization of the process of anaerobic digestion of organic waste in laboratory bioreactors at 20 and 50 degrees C to use a mixture of activated suspension of soil from the anaerobic zone of the landfill and digested sewage sludge. Stimulation of methanogenesis was shown in field conditions when digested sewage sludge was added directly into the upper layer of anaerobic zone of the landfill. The investigation of methane production during fermentation of concentrated food waste with a mixture of excessive activated sludge in the laboratory under thermophilic conditions (50 degrees C) has shown that the main problem at the first stage of the process was the acidification of the digested mixture due to the accumulation of volatile fatty acids. It was shown that for stable operation of the bioreactor under thermophilic conditions the amount of inoculum added during the start up should be no less than 30%-50%--based on volatile suspended solids. A sharp decrease in the digestion temperature from 50 to 20 degrees C did not cause methanogenesis termination, since the thermophilically fermented biomass contained both thermophilic and mesophilic methanogens. PMID- 26353403 TI - A NOVEL OLEAGINOUS YEAST STRAIN WITH HIGH LIPID PRODUCTIVITY AND ITS APPLICATION TO ALTERNATIVE BIODIESEL PRODUCTION. AB - Five lipid-producing yeast strains, CHC08, CHC11, CHC28, CHC34, and CHC35, were revealed by Sudan Black B staining to contain lipid droplets within cells. Molecular analysis demonstrated that they were 2 strains of Candida parapsilosis, Pseudozyma parantarctica, Pichia manshurica, and Pichia occidentalis. Following batch fermentation, P. parantarctica CHC28 was found to have the highest biomass concentration, total lipids and lipid content levels. The major fatty acids in the lipids of this yeast strain were C16 and C18. Predictions of the properties of yeast biodiesel using linear equations resulted in values similar to biodiesel made from plant oils. Preliminary production of yeast biodiesel from P. parantarctica CHC28 was accomplished through esterification and transesterification reactions. It was found that yeast lipids with high acid value are easily converted to biodiesel at an approximately 90% yield. Therefore, it is possible to use crude lipids as alternative raw materials for biodiesel production. PMID- 26353404 TI - [Total Peroxidase and Catalase Activity of Luminous Basidiomycetes Armillaria borealis and Neonothopanus nambi in Comparison with the Level of Light Emission]. AB - The peroxidase and catalase activities in the mycelium of luminous basidiomycetes Armillaria borealis and Neonothopanus nambi in normal conditions and under stress were compared. An increase in the luminescence level was observed under stress, as well as an increase in peroxidase and catalase activities. Moreover, the peroxidase activity in extracts of A. borealis mycelium was found to be almost one and a half orders of magnitude higher, and the catalase activity more than two orders of magnitude higher in comparison with the N. nambi mycelium. It can be suggested that the difference between the brightly luminescent and dimly luminescent mycelium of N. nambi is due to the content of H2O2 or other peroxide compounds. PMID- 26353405 TI - [Construction of Producers of Cellulolytic and Pectinolytic Enzymes Based on the Fungus Penicillium verruculosum]. AB - Based on the fungus Penicillium verruculosum, we created strains with a complex of extracellular enzymes that contains both cellulolytic enzymes of the fungus and heterologous pectin lyase A from P. canescens and endo- 1,4-alpha polygalacturonase from Aspergillus niger. The endopolygalacturonase and pectin lyase activities of enzyme preparations obtained from culture media of the producer strains reached 46-53 U/mg of protein and 1.3-2.3 U/mg of protein, respectively. The optimal temperature and pH values for recombinant pectin lyase and endopolygalacturonase corresponded to those described in the literature for these enzymes. The content of heterologous endopolygalacturonase and pectin lyase in the studied enzyme preparations was 4-5% and 23% of the total protein content, respectively. The yield of reducing sugars upon the hydrolysis of sugar beet and apple processing wastes with the most efficient preparation was 41 and 71 g/L, respectively, which corresponded to a polysaccharide conversion of 49% and 65%. Glucose was the main product of the hydrolysis of sugar beet and apple processing wastes. PMID- 26353406 TI - [Salt Stress Response in Arabidopsis thaliana Plants with Defective Jasmonate Signaling]. AB - The effects of exogenous jasmonic acid (JA) on antioxidant enzymes in four-week old leaves of wild-type Arabidopsis thaliana L. (Columbia-0) and jin1 (jasmonate insensitive 1) mutant plants with defective jasmonate signaling were investigated under normal conditions and under salt stress (200 mM NaCl, 24 h). The wild-type plants responded to JA by an increase in the activities of Cu/Zn superoxide dismutase, catalase, and guaiacol peroxidase, while there was no change in the case of the mutant plants. In response to the salt stress of both the wild-type and mutant genotypes, the activities of superoxide dismutase, catalase, and guaiacol peroxidase were unchanged, decreased, and increased, respectively. The JA-treated wild type plants showed the highest activity of all three enzymes as compared with the mutant plants. Salinity caused a decrease in chlorophyll content in the wild-type and jin 1 plants. Preliminary JA treatment of the Col-0 plants resulted in a normal content of photosynthetic pigments after the salt stress, while the positive JA effect was insignificant in the jin 1 mutants. It was concluded that the MYC2/JIN 1 protein is involved in the JA signal transduction and plant adaptation to salt stress. PMID- 26353407 TI - [Inhibition of Linseed Oil Autooxidation by Essential Oils and Extracts from Spice Plants]. AB - Clove bud essential oil, extracts from ginger, pimento and black pepper, or ascorbyl palmytate were studied as natural antioxidants for the inhibition of autooxidation of polyunsaturated fatty acids in linseed oil. Different methods were used to estimate antioxidant efficiency. These methods are based on the following parameters: peroxide values; peroxide concentration; content of degradation products of unsaturated fatty acid peroxides, which acted with thiobarbituric acid; diene conjugate content; the content of volatile compounds that formed as products of unsaturated fatty acid peroxide degradation; and the composition of methyl esters of fatty acids in samples of oxidized linseed oil. PMID- 26353408 TI - [Effect of pH of Adsorption Buffers on the Number and Antigen-Binding Activity of Monoclonal Antibodies Immobilized on the Surface of Polystyrene Microplates]. AB - The change in the concentration and antigen-binding activity of 28 monoclonal antibodies was studied after their adsorption on the surface of polystyrene microplates in buffers with different pH values (1.0, 2.8, 7.5, 9.6, and 11.9). We used 16 clones to the HIV p24 protein and 12 clones to the surface antigen of Hepatitis B Virus. The binding efficiency of adsorbed antibodies to the labeled antigen was evaluated by the slope of the linear region of the binding curve to the concentration axis. It was shown that the antigen-binding activity of six antibodies (21.5%) statistically significantly increased after adsorption at pH 2.8 and 11.9 as compared to pH 7.5 and 9.5. The maximum amount of antibodies was found to be adsorbed on the solid surface at pH 7.5. The analysis of the binding of 125I-HBs-antigen to adsorbed antibodies made it possible to evaluate the concentration of active antibodies on the polystyrene surface. It was shown that the increase in the antigen-binding activity was due to an increase in the proportion of antibodies with retained activity after adsorption at pH 2.8 and 11.9. Under these conditions, about 20% of the antibodies retained their antigen binding activity, and 6% did so after immobilization at pH 7.5. PMID- 26353409 TI - [Biologically Active Peptides of King Crab Hepatopancreas]. AB - Substances of a peptide nature isolated from the hepatopancreas of the king crab Paralithodes camtschaticus exhibited physicochemical properties and membranotropic and specific activities similar to those of membranotropic homeostatic tissue-specific bioregulators previously found in different mammalian and plant tissues. Their biological effect on vertebrate tissues was demonstrated on a model of roller organotypic cultivation of Pleurodeles waltl newt liver tissue. PMID- 26353410 TI - Diversity of Arbuscular Mycorrhizal Fungi in the Growth Habitat of Kayu Kuku (Pericopsis mooniana Thw.) In Southeast Sulawesi. AB - Arbuscular Mycorrhizal Fungi (AMF) are categorized as fungi which have symbioses with terrestrial plants and are distributed in various habitat types. The objectives of this research were to investigate the diversity of AMF in stands of kayu kuku (Pericopsis mooniana Thw.) in Southeast Sulawesi. Collection of samples of soil and root were conducted in six locations. Isolation of spores used the method of wet sieving and decanting, whereas AMF identification was conducted by observing morphology of AMF spores. Parameters of AMF diversity, namely species richness, diversity index, dominance index, evenness index and colonization were studied using method of infected root length. Research results showed that location differences affected significantly the spore density and parameters of AMF diversity, except colonization of AMF (p < 0.116). Location around the Governor office showed the highest number of spores (208.6 spores/100 g of soil). Soil chemical properties, such as C, N, P and heavy metal contributed towards AMF spore density and diversity. Soil C and N correlated negatively with spore density. In terms of location, Glomeraceae constituted the genera with the largest number of species and possessed wide distribution in all research locations. In general, natural forest has higher AMF diversity index (Shannon Weiner diversity index-H'), evenness (E) and species richness (S) as compared with location of PT. Vale Indonesia Tbk. PMID- 26353411 TI - Effects of Oral Vitamin C Supplementation on Anxiety in Students: A Double-Blind, Randomized, Placebo-Controlled Trial. AB - Vitamin C ascorbic acid) is a well-known antioxidant that is involved in anxiety, stress, depression, fatigue and mood state in humans. Studies have suggested that oxidative stress may trigger neuropsychological disorders. Antioxidants may play an important therapeutic role in combating the damage caused by oxidative stress in individuals that suffer from anxiety. In this context, it was hypothesized that oral vitamin C supplementation would reduce anxiety. However, few up to date studies have evaluated the consequences of oral vitamin C supplementation on anxiety in humans. The present study examined the effects of oral vitamin C supplements in 42 high school students, in a randomized, double-blind, placebo controlled trial. The students were given either vitamin C (500 mg day(-1)) or placebo. Plasma concentrations of vitamin C and blood pressure were measured before the intervention and then one day after the intervention. Anxiety levels were evaluated for each student before and after 14 days following supplementation with the Beck Anxiety Inventory. Results showed that vitamin C reduced anxiety levels and led to higher plasma vitamin C concentration compared to the placebo. The mean heart rates were also significantly different between vitamin C group and placebo control group. Present study results not only provide evidence that vitamin C plays an important therapeutic role for anxiety but also point a possible use for antioxidants in the prevention or reduction of anxiety. This suggests that a diet rich in vitamin C may be an effective adjunct to medical and psychological treatment of anxiety and improve academic performance. PMID- 26353412 TI - Changes in Protein Expression in Peanut Leaves in the Response to Progressive Water Stress. AB - This investigation was carried out at the Department of Plant Science and Agricultural Resources, Khon Kaen University in the rainy season of 2011. The objective of this study was to identify proteins in leaves of drought-susceptible peanut plants when regulated by progressive water stresses. The drought susceptible peanut plants of Khon Kaen 4 cultivar were grown in pots under controlled environment. At day 30 after seed emergence, the plants were subjected to stress conditions for 5 and 6 days. The results showed that withheld water supply for 5 and 6 days gave moderately and severely water stresses, respectively. Under moderate water stress conditions, two up-regulated and eight down-regulated proteins were attained. The up-regulated proteins were striated fibre assembling and flap endonuclease 1. The down-regulated proteins were peptidyl-prolyl cis-trans isomerase FKBP4, tRNA(Ile)-lysidine synthase, chloroplastic, chloroplastic thioredoxin F-type, cytidinedeaminase 7, ALF domain class transcription factor, nudix hydrolase 8, pentatricopeptide repeat super family protein, putative and ribulose-1,5-bisphosphate carboxylase/oxygenase, a large sub-unit. Under severe water stress conditions, two proteins, i.e., tRNA(Ile) lysidine synthase, chloroplastic and ALF domain class transcription factor did not change their relative abundance significantly where it indicated drought acclimation. The remaining proteins displayed significant changes and the changes were the same as those found in the peanut leaves when deprived water for 5 days. Up-regulated proteins are responsible for alleviating oxidative damages to plant genome and mediating plants responsive to the environmental factors in providing mechanical support, barriers and a rapid transport route. Down regulated proteins were associated with drought susceptibility of the Khon Kaen 4 peanut plants. PMID- 26353413 TI - Degradability of Treated Ethion Insecticide by TiO2 Photocatalysis. AB - Ethion, an insecticide, is widely used with fruit and vegetable crops. This research studied the reduction and oxidative degradation of standard ethion by TiO2 photocatalysis. A standard ethion solution (1 mg L(-1)) was treated with different concentrations of TiO2 powder (5, 10, 20, 40 and 60 mg mL(-1)) for 0, 15, 30, 45 and 60 min. The amount of ethion residue was detected by gas chromatography with flame photometric detection (GC-FPD) and the concentration of anions produced as major degradation products was determined by Ion Chromatography (IC). The TiO2 photocatalysis efficiently reduced ethion concentrations, with the highest degradation rate occurring within the first 15 min of reaction. The reaction produced sulphate and phosphate anions. The TiO2photocatalysis reduced 1 mg L(-1) ethion to 0.18 mg L(-1) when treated with 60 mg mL(-1) TiO2 powder for 60 min. The lethal concentration (LC50) of standard ethion was also estimated and compared to the treated ethion. All treatments, especially 60 mg mL(-1) TiO2 powder, markedly detoxified ethion, as tested with brine shrimp (Artemia salina L.), with an LC50 value of 765.8 mg mL(-1), compared to the control of 1.01 mg mL(-1). PMID- 26353414 TI - Flexor Tendon Injuries and Treatment Results of 67 Patients. AB - Flexor tendon injury is the most commonly seen hand injury. Tendons are the structures which enable the muscles to adhere to the bones and transmit the movement starting from the muscle to the bones. They have significant role in hand movement. As treatment method, surgical repair: (1) Primary repair, (2) Secondary repair; techniques are used. With the scientific studies conducted, flexor tendon morphology, kinematics, biomechanics, biological properties and tendon improvement became quite understandable, good suturing materials were developed and consequently successful studies regarding primary repair results were published. Flexor tendon surgery has reached its current level with the accumulation of knowledge obtained from the increased clinical and experimental studies. This study addresses flexor tendon injuries and surgical treatment methods. We achieved 76.12% full functioning fingers in the results; we obtained following the physical treatment application that started on the 10th day after primary repair that we performed in 67 patients who applied with acute flexor tendon Zone 1-2 and 3 incision. Flexion restriction and contracture developed in 16 patients (23.88%) at various levels. Scar softening and revision surgery for contracture excision was performed in 8 patients (11.94%) with Zone 2 injury due to contracture. Superficial skin infection developed in 21 patients (31.34%) and was treated. Revision surgery was performed in 6 patients with Zone 1 injury due to rupture occurred during rehabilitation. PMID- 26353415 TI - In vivo Induction of Tetraploid in Tangerine Citrus Plants (Citrus reticulata Blanco) with the Use of Colchicine. AB - This in vivo experiment was carried out at Sakhon Nakhon Rajabhat University, Sakhon Nakhon Province, Thailand during March-October 2013. The study aims to search for some possibilities in inducing a large number of tetraploid sets of chromosomes in tangerine citrus seedlings with the use of colchicine chemical. A Randomized Complete Block Design (RCBD) with four replications was used. Seeds of tangerine citrus were treated with colchicine solutions. The experiment consisted of seven treatments, i.e., T1 with 0.0% colchicine (control), T2 with 0.2% colchicine solution and submerged for 12 h, T3 with 0.2% colchicine solution and submerged for 24 h, T4 with 0.4% colchicine solution and submerged for 12 h, T5 with 0.4% colchicine solution and submerged for 24 h, T6 with 0.8% colchicine solution and submerged for 12 h, T7 with 0.8% colchicine solution and submerged for 24 h. The experiment was conducted for 91 days. The results showed that colchicine compound severely and significantly affected germination of tangerine citrus seeds. Colchicine of 0.2% in the solution with seeds submerged for 24 h gave the highest percentages of tetraploid chromosomes in seedlings of tangerine citrus (63.64%). Colchicine significantly affected seed germination, plant height, stomata density and leaf index of the tangerine citrus seeds and seedlings. Colchicine had no significant effect on poly-embryos, mono-embryos, leaf number, leaf area, leaf weight, leaf length and stomata length of the tangerine citrus seedlings. PMID- 26353416 TI - Screening for Endophytic Fungi from Turmeric Plant (Curcuma longa L.) of Sukabumi and Cibinong with Potency as Antioxidant Compounds Producer. AB - Potency of medicinal plant is related to microorganisms lived in the plant tissue. Those microorganisms are known as endophytic microbes that live and form colonies in the plant tissue without harming its host. Each plant may contains several endophytic microbes that produce biological compounds or secondary metabolites due to co-evolution or genetic transfer from the host plant to endophytic microbes. Endophytic fungi research done for turmeric plant (Curcuma longa L.) gave 44 isolated fungi as results. Those 44 fungi isolated were fermented in Potato Dextrose Broth (PDB) media, filtered, extracted with ethylacetate and then were analyzed by Thin Layer Chromatography (TLC) method and tested for their antioxidant activity by radical scavenging method. The antioxidant activity of the ethylacetate filtrate extracts either from Sukabumi or Cibinong were higher than the biomass extracts. There were 6 fungi that showed antioxidant activities over 65%, i.e., with code name K.Cl.Sb.R9 (93.58%), K.Cl.Sb.A11 (81.49%), KCl.Sb.B1 (78.81%), KCl.Sb.R11 (71.67%) and K.Cl.Sb.A12 (67.76%) from Sukabumi and K.Cl.Cb.U1 (69.27%) from Cibinong. These results showed that bioproduction by endophytic microbes can gave potential antioxidant compounds. PMID- 26353417 TI - Acute and Cytotoxicity Studies of Aqueous and Ethanolic Leaf Extracts of Chromolaena odorata. AB - Chromolaena odorata, a commonly used traditional remedy for different ailments, believed to be quite safe in terms of toxicity was evaluated for acute toxicity and cytotoxic potentials. Acute toxicity was done on albino Wistar rats using the Lorke method while brine shrimps were used to test for cytotoxicity. The results showed that the estimated LD50 for the aqueous and ethanolic extracts was 2154 and > 5000 mg kg(-1) body weight, respectively. Cytotoxicity to brine shrimps showed LC50 values of 324 and 392 ppm for aqueous and ethanolic extracts, respectively. These results indicate the relative non toxic nature of Chromolaena odorata extracts. PMID- 26353418 TI - AN APPRAISAL OF RETAINED PLACENTA AT THE UNIVERSITY OF PORT HARCOURT TEACHING HOSPITAL: A FIVE-YEAR REVIEW. AB - BACKGROUND: Retained placenta is associated with an increased risk of maternal morbidity and mortality especially in developing countries. OBJECTIVE: To determine the incidence and evaluate the mode of presentation, risk factors and method of treatment of patients with retained placenta. METHODOLOGY: A retrospective review of retained placenta managed at the University of Port Harcourt Teaching Hospital (UPTH), Port Harcourt over a 5 year period (January 2009 to December 2013). Data obtained were analyzed using statistical software SPSS 17.0. RESULTS: There were 93 cases of retained placenta out of 15,789 deliveries, giving an incidence of 0.59%.85 patients' case records were available for analysis. Majority of the patients 69 (81.2%) were unbooked (had no antenatal care) with 60 (70.6%) having home deliveries. Previous history of dilatation and curettage and preterm deliveries, accounted for the major identifiable risk factors at 55 (64.7%) and 22 (25.9%) respectively. At presentation, 22(25.9%) were in hypovolemic shock. Manual removal of the placenta was the commonest treatment modality (87.1%).There was one maternal death giving rise to a case fatality rate of 1.18%. CONCLUSION: Retained placenta is a major cause of maternal morbidity and mortality from postpartum haemorrhage and other complications related to its removal. The incidence can be reduced by antenatal care, skilled birth attendance and provision of emergency obstetrics care services. PMID- 26353419 TI - LIMITED ELEVATIONS IN ANTITUBERCULOSIS DRUG-INDUCED SERUM ALANINE AMINOTRANSFERASE (ALT) LEVELS IN A COHORT OF NIGERIANS ON TREATMENT FOR PULMONARY TUBERCULOSIS AND HIV INFECTION IN YENAGOA. AB - BACKGROUND: This study, undertaken in a major tertiary hospital in the Niger Delta region of Nigeria was designed to examine the incidence of elevation in serum alanine aminotransference (ALT) in our patients who were on treatment for HIV/AIDS with some of them on antituberculosis drugs. METHOD: Between January and December 2014, all admission records which include HIV status, Acid fast bacilli Status, Chest radiograph, CD4 cell count, degree of hepatotoxicity during antituberculosis drugs treatment according to WHO definition using clinical findings and ALT levels at baseline (ALTI) and at 4 weeks into treatment with antituberculosis drugs (ALT2) of all the patients on HAART with some on antituberculosis drugs were retrieved and retrospectively analyzed. RESULTS: Of the total of 707 patients on HAART, 80 were on both HAART and anti-tuberculosis treatment.There was a statistically significant correlation between ALT I levels in the PTB negative and PTB positive cohort at baseline chi2 10.725,d.f4,P = 0.030. After 4 weeks of antituberculosis treatment and HAART ALT2 level in expectedly, generally showed downward trend with no statistically significant correlation between PTB status and ALT2 (chi2 = 0.789, d.f2.P = 0.674) CONCLUSION: Anti-tuberculosis drug induced elevation in alanine amino transference is unexpectedly low in our patients on treatment for pulmonary tuberculosis and HIV infection. This is a key finding that requires further studies. PMID- 26353420 TI - HEALTH WORKERS' PERCEPTIONON THE QUALITY OF SERVICE AND CORPORATE CULTURE OF A TEACHING HOSPITAL IN NIGERIA. AB - BACKGROUND: Quality of service delivery remains the most important issue in hospitals since patients expect higher standard care and services. This quality service is rooted in the culture of the health care organization. Therefore,this study seeks to determine health workers' perception on the quality of service and corporate culture at University of Uyo Teaching hospital, Uyo, Nigeria. METHOD: A cross-sectional descriptive study was carried out. Using structured questionnaire and convenient sampling technique, data were collected from 250 hospital workers.The responses on questions to elicit the hospital's quality of service and corporate culture were rated on a five-point Likert Scale as follows; Strongly Agree (SA), Agree (A), Neutral(N), Disagree (D) and Strongly Disagree (SD). Data entry and analysis were performed using Epi Info 3.2.2 (CDC, Atlanta, Georgia, USA). RESULTS: The minimum and maximum ages of the respondents were 21 years and 60 years respectively. The mean, median and mode ages in the respondents were 34.6 (+/- 7.88) years, 33 years, and 30 years respectively. Majority of the study respondents were in the age group of 31-40 years (30%), female (56.8%) and Doctors (36%). The respondents' positive perception on quality of service offered by the hospital was 69.2% (OR 5.05, 95% CI 3.39-7.52, P < 0.00001). The subjects' positive perception on the organization values for the individual worker was 54.4% (OR 1.42, 95% CI 0.99- 2.06, P = 0.049). However, only 43.2% of the subjects accepted that the management of the hospital was flexible and understands the important of balancing their work/personal life (OR 0.58, 95%CI 0.40-0.84), P = 0.002).Thirty-eight percentages (38%) accepted that top management of the hospital communicates changes in decisions that affect employees (OR 0.38, 95% CI 0.26-0.55), P < 0.00001). Majority of the workers in the various professions accepted that the hospital offer quality services as obtained in other hospitals. Majority of the workers in all the professions except Medical Doctors accepted that the hospital values the individual workers. Majority of the Pharmacists and Non-clinical staff accepted that the hospital management was flexible and understands the importance of balancing their work and personal life. Majority of the Doctors, Pharmacists and laboratory/image scientists did not accept that top management communicates changes in decisions that affect employees. CONCLUSION: The perception of health workers on the quality of service rendered by the University of Uyo Teaching Hospital was satisfactory. However, the hospital needs to improve on its corporate culture to achieve a higher quality of service. PMID- 26353421 TI - EPIDEMIOLOGY OF DIABETES AND IMPAIRED FASTING GLUCOSE IN A RURAL COMMUNITY OF NIGERIAN NIGER DELTA REGION. AB - BACKGROUND: The prevalence of diabetes mellitus is reaching epidemic rates globally. It had an estimated global incidence of 220 million in 2010. Different studies in SSA and Nigeria in particular have reported increasing prevalence of diabetes in the rural areas. This may be attributed to the rapid 'westernization' of lifestyle in the rural African community.Only few rural survey have been conducted in the Nigeria oil-rich Niger Delta region necessitating this study with the aim of determining the prevalence of diabetes and impaired fasting glucose (IFG). METHODS: This was a cross-sectional survey involving 500 subjects aged 15 years and above in a typical rural community of Rivers State, Niger Delta region of Nigeria. A questionnaire administered by face-to-face interview was used to assess socio-demographic characteristics of the subjects. Medical history such as prior knowledge of blood sugar status and family history of diabetes were all elicited by the questionnaire. Anthropometric and blood pressure measurements were taken in a standardized manner and body mass indices (BMI) calculated as weight in kilogram divided by the square of height in meters. Venous blood glucose was measured by the glucose oxidase method. Diabetes mellitus was defined using fasting plasma glucose (FPG) >= 7.0 mmol/l (126 mg/dl) and individuals who were previously known to have diabetes based on history of treatment were also classified to have diabetes. Lipid profile and uric acid of patients were also checked. RESULTS: There were 156 males and 344 females with male to female ratio of 1:2.3.The females were relatively of younger age than the males (40.62 +/- 16.6 years versus 42.84 +/- 17.8).The overall mean age was 41.32 +/- 17. The mean fasting plasma glucose among those with diabetes was 11.14?4. 00mmol/L while the mean for the subjects with impaired fasting glucose was 6.31 +/- 0.25 mmol/l. The prevalence of diabetes was 2.2% with no significant gender difference (2.6% in males versus 2.0% in females; chi2 = 0.35; p = 0.84). The prevalence of Impaired fasting glucose (IFG) was 2.4%with no significant gender difference (Female 2.6% versus males 1.9%; p = 0.88). The mean fasting glucose increased significantly with blood pressure (p = 0.05), waist circumference (p < 0.001), uric acid level (0.02), triglyceride level (< 0.001) and age (p = 0.02).The correlation analyses showed that age, systolic blood pressure, waist-hip-ratio and triglycerides are positively correlated with diabetes and impaired fasting glucose in this study. CONCLUSION: There is a low prevalence of diabetes and IFG in this rural community which may be associated to the high level of physical activity found among the study subjects in this community. However, this study confirmed that increasing age, abdominal obesity, systolic blood pressure and triglyceride level have positive relationship with the prevalence of diabetes and IFG. There is hence more need for intensified screening for diabetes, pre-diabetes and associated risk factors in order to curb or at least reduce diabetes prevalence and its attendant complications. PMID- 26353422 TI - DIABETIC FOOT ULCERS -12 MONTHS PROSPECTIVE REVIEW OF PATTERN OF PRESENTATION AT ENUGU STATE UNIVERSITY OF TECHNOLOGY TEACHING HOSPITAL, PARKLANE, ENUGU: A BASIS FOR DIABETIC FOOT CLINIC? AB - INTRODUCTION: Diabetic foot ulcer is a common complication of diabetes. This morbidity results in long hospitalization and high cost of management. It is a significant cause of non-traumatic amputation. Reduction in incidence and progression to amputation will be highly desired. AIM: To highlight the pattern of presentation and to emphasize the need for multidisciplinary approach in prevention by integration of focused footcare plan. PATIENTS AND METHODS: A prospective interviewer administered questionnaire based study. RESULTS: A total of 36 patients were recruited with a male female ratio of 1.8:1. Mean age of presentation was 55.5 years and commoner in those that have had diabetes for 10 - 15 years. Low level of education had a direct relationship with occurrence of DFU. Neuropathy was a common predisposing factor to DFU. More than 60% had no knowledge of foot care even though they have been educated on dietary control here was average hospital stay of 48 days, amputation rate of 19.4% and mortality rate of 8.3%. CONCLUSION: A comprehensive foot care program should be incorporated in the management of diabetes as soon as diagnosis is made in other to reduce the huge burden of DFU. PMID- 26353423 TI - PATTERNS OF SEMINAL FLUID ANALYSIS IN MALE PARTNERS OF INFERTILE COUPLES ATTENDING GYNAECOLOGY CLINIC AT FEDERAL MEDICAL CENTRE, ABEOKUTA. AB - BACKGROUND: Infertility affects 19% of the general population I, and this constitutes a reproductive health concern for the affected couples. The contribution of male factors as cause of infertility is increasingly being noted in the recent times and has become a source of concern to the affected couples with its attendant social and psychological effects and with the potential of threatening relationships. OBJECTIVES: To assess the seminal fluid analysis parameters in male partners of infertile couples presenting at gynaecological clinic of Federal Medical Centre, Abeokuta and to determine the patterns of seminal fluid abnormalities in the seminalysis results. METHODOLOGY: The study is a 3 year retrospective review of seminal fluid analysis results of male partners in infertility cases at the Federal Medical Centre Abeokuta. Analysis was done using the WHO laboratory manual for the examination and processing of human semen revised fifth edition. RESULTS: During this study period, a total of 214 semen samples were analysed for semen quality over a 3 year period. Sixty four (30%) of the men had normal semen parameters, while one hundred and fifty (70%) had abnormal semen parameters. The abnormal semen parameters consists of low volume (12.6%), prolonged liquefaction time (9.8%), oligospermia (28%), azoospermia (8%), asthenozoospermia (25%), teratozoospermia (9%), combined defects of oligo asthenozoospermia (23.8%), oligo-teratozoospermia (9.8%), asthenoteratozoospermia (12.60%) and oligoasthenoteratozoospermia (11.20%). CONCLUSION: This study has confirmed that male factor infertility remains a significant contributor to infertility in our environment. Efforts should be made in enlightening men on the common aetiologies of abnormal semen and options of treatment of likely causes. PMID- 26353424 TI - CRYSTALLOID PRELOAD SHOWS TRANSIENT SUPERIORITY OVER COLLOID, OR THEIR COMBINATION IN SPINAL ANAESTHESIA-INDUCED HYPOTENSION PROPHYLAXIS FOR CAESAREAN SECTION. AB - BACKGROUND: Many studies comparing different intravenous fluid types usually do not use equipotent volumes of 3:1 crystalloid: colloid ratio in such comparisons. Conflicting results emanate from such studies. This study was designed to compare the efficacy of equipotent volumes of crystalloid, colloid and combination of crystalloid/colloid in spinal anaesthesia-induced hypotension prophylaxis. METHODOLOGY: Pregnant women scheduled for elective Caesarean section were prospectively randomized to three groups to each received either 1 500 ml of Ringers lactate, or 500 ml of 6% pentastarch or a combination of 250 ml of 6% pentastarch and 750 ml of Ringers lactate intravenous fluid preload, before spinal anaesthesia. Hemodynamic variables were monitored. RESULTS: First 10 minutes, crystalloid showed better efficacy in hypotension prophylaxis over the other regimen. In the next 30 minutes however, there were no significant differences between the groups. CONCLUSION: Crystalloids proved more effective than colloid or their combination in hypotension prophylaxis in the first 10 minutes after spinal anaesthesia. PMID- 26353425 TI - MEDICAL AUDIT OF PATIENT CARE: A STUDY OF DOCTORS IN A TERTIARY HEALTH FACILITY IN SOUTH WEST NIGERIA. AB - INTRODUCTION: The role of Medical Audit in patient care needs to beexplored. This study aimed to determine doctors' knowledge and practice of Medical Audit in a tertiary health facility in South West Nigeria. METHODS: Across-sectional study of 115 consenting doctors at Federal Medical Centre Owo was conducted. A semi structured, self-administered questionnaire was used. Data was analyzed using SPSS version 21. Descriptive statistics were presented using frequency tables and bar chart, age and year of practice were summarized as mean and standard deviation. Chi square-test was used to compare sociodemographic variables with doctor's knowledge of MedicalAudit. Level of statistical significant was 5%. RESULT: The mean age of the respondents was 32.5 +/- 5.8 years. Males were 78%, and 61.7% were married. The mean duration of practice was 3.3 +/- 2.2 years. Adequate knowledge of Medical Audit was found in 79% of the respondents while only 53% had practiced it. Formal training on Medical Audit has not been received by 91.3% of the respondents, 80.9% requested for training on Medical Audit. In all, 88.0% who had >= 3-years of practice had adequate knowledge compared with only 72.3% of those who had less than three years of practice (p = 0.040). CONCLUSION: Practice of MedicalAudit is low though adequate knowledge exist.Training of doctors on Medical Audit is required. PMID- 26353426 TI - MESENCHYMAL TUMOURS OF THE GASTROINTESTINAL TRACT: THE IMPORTANCE AND USE OF IMMUNHISTOCHEMISTRY IN CHARACTERIZING SPECIFIC TUMOUR ENTITIES. AB - BACKGROUND: Mesenchymal Gastrointestinal (GI) tumours are heterogenous group of tumours. Prior to 2005, immunohistochemistry (IHC) was not used in diagnostic pathology to characterize these tumours at our centre. OBJECTIVES: To subclassify mesenchymal tumours in the GI tract and related locations into Gastrointestinal stromal tumour (GIST) and non-GIST tumours using specific IHC antibody markers. METHODS: Formalin Fixed Paraffin Embedded tumour tissue over the period 1991- 2004 were retrieved, from the files and records of the Department of Pathology, University College Hospital, Ibadan, Nigeria. Haematoxylin and Eosin slides of such cases were reviewed. The IHC expressions of c-Kit, CD 34, alpha-smooth muscle actin, desmin and S-100 were evaluated in these tumours. RESULTS: Based on morphology and IHC staining pattern, 24 of the 46 cases were identified as GIST by c-kit positivity. Nine of the cases were smooth muscle tumours (4- leiomyoma and 5- leiomyosarcoma), 8 cases of undifferentiated sarcomas, 4 cases of desmoid and one case of inflammatory myofibroblastic tumour. For GISTs: The male:female ratio is 1.2. The age range of the patients was 11-75 years with a mean age of 55.1 years.Tumour size ranged from 7-32 cm with an average of 19.8cm and average mitotic count of 20 per 50 high power field. The location of the GIST tumours were as follow- stomach- 9 cases (37.5% of the 24 GIST cases), colon and rectum 6 (25%), Abdominal cavity (omentum/ mesentery)- 6 (25%), retroperitoneum-2(8.3%), small intestine-1 (4.2%). CONCLUSION: The use of IHC in this study has helped to segregate and distinguish GI mesenchymal tumours into different sub-types, majority being Gastrointestinal stromal tumours. PMID- 26353427 TI - TUBERCULOSIS CONTROL IN SECURITY CHALLENGED STATES OF NORTH-EAST NIGERIA. ARE THERE SIGNIFICANT IMPACT?. AB - BACKGROUND: Nigeria in the past few years is faced with various security challenges in different parts of the country. The most severe in the last three years has been the crisis in northern Nigeria and specifically the north-eastern States, where three of the States have been under emergency rule for a year. Health care delivery system is usually one of the major casualties in a security challenged environment leading to unavailability or low utilization of services.The aim of this paper is to share the experience of TB services in states under emergency rule. METHODOLOGY: A retrospective review of program data (reportable indicators for TB case finding,TB/HIV and treatment outcome for periods of eight years (2006-2013) comparing national data with north-east and the three states most affected by security challenges (Borno, Adamawa & Yobe). RESULTS: A national positive trend on case notification for all forms of TB and smear positive, with a declined in 2011 but generally the case notification has remain low (59/100,000 in 2013 compared to estimated prevalence of 338/100,000). North east data is a negative trend for case notification and this is worse for 2 states (Borno and Yobe) while Adamawa shows and increase CNR from 2012 because of TB Reach active case, finding. Treatment success rate has a positive trend both national, north east states and in the 3 challenged states (TSR above 84%). TB/HIV indicators for north east are 81%, 75%, and 58% for HCT CPT and ART respectively, these figures has serious fluctuations within and among the three security challenged states with Borno most affected. CONCLUSIONS: Insecurity can pose a challenge for TB control activities especially case finding, therefore the need for innovative approaches for case finding in areas of insecurity. Chronic infectious diseases like TB and HIV should be incorporated into emergency responses offered by organisations and agencies for internally displaced persons. PMID- 26353428 TI - EVALUATION OF MALE SEX HORMONES AND TRACE ELEMENTS IN MALE TYPE 2 DIABETIC PATIENTS ATTENDING NNAMDI AZIKIWE UNIVERSITY TEACHING HOSPITAL DIABETIC CLINICS. AB - BACKGROUND: There is accumulating evidence that the metabolism of male sex hormones and several trace elements are altered in type 2 diabetic mellitus and may have specific role in the pathogenesis and progression of the disease. AIM: To assess the levels of male sex hormones and trace elements in type 2 diabetic patients and to ascertain an association between male sex hormones and trace elements among diabetic subjects. METHODS: A descriptive cross sectional study was conducted among 125 diabetic and 50 non diabetic subjects. Venous blood samples were collected from all respondents and estimated for fasting blood glucose, male sex hormones and trace elements. The results were subjected to statistical analysis and comparison using Students' test and Pearson correlation analysis. RESULTS: The mean testosterone level was significantly lower in diabetics than in controls (3.9 +/- 1.9ng/ml) in comparison with (5.1 +/- 1.7ng/ml; P < 0.05). The mean value of Zinc, Manganese, Selenium and Chromium were significantly lower among the diabetics when compared with the controls (Zn;898.7 +/- 131.0 MUg/l; Mn:0.30 +/- 0.06 MUg/l;Se:51.3 +/- 11.1 MUg/l; Cr: 0.04 +/- 0.03 MUg/I) in comparison with (Zn: 1007.3 +/- 85.2 MUg/l; Mn: 0.05 +/- 0.07MUg/l; Se: 62.1 +/- 11.1 MUg/l; Cr: 0.06 +/- 0.01 MUg/l; P < 0.05).The mean Fasting Blood Glucose in diabetic subjects was significantly higher when compared with the controls (7.9 +/- 3.7 mmol/l) in comparison with (4.6 +/- 0.4 mmol/l; P < 0.05).The trace elements showed a positive correlation with testosterone in diabetic subjects (Zn r = 0.359, Ser = 0.443, Mn r = 0.350, P < 0.05). CONCLUSION: This study observed decreased levels of testosterone and trace elements in type 2 diabetics and a positive correlation between low testosterone and low trace elements levels in diabetic subjects. These trace elements are antioxidants and their low levels in diabetic patients may further increase the severity of the disease. PMID- 26353429 TI - RETROSPECTIONS ON ROAD TRAFFIC INJURIES AS A SOCIAL BURDEN: THE ROLE OF PUBLIC HEALTH EDUCATION INITIATIVES IN A DEVELOPING COUNTRY. AB - BACKGROUND: Road traffic injuries are a major cause of trauma related morbidity and mortality in our modern society. They have since been recognized as disease entities on their own, as well as a societal problem of serious public health concern. AIM: The aim of this review article is to promote the understanding of road traffic injuries as both a social burden and a disease entity and to highlight suggested measures capable of curtailing the menace that these injuries pose to human population. METHOD: A review of the literature on the subject of road traffic injuries as both a social problem and disease entity was done. Historical perspectives, epidemiological information, causative factors and preventive measures were extracted and presented. RESULT: Human factors contribute to 95% of road traffic accident. Current deaths from road traffic injuries account for 2.2% of the global mortality affecting all age groups. Health education and enforcement of legislation are key measures in combating road traffic injuries. PMID- 26353430 TI - OTOLOGIC FOREIGN BODY: AN UNDECLARED AND UNUSUAL IMPACTION. AB - BACKGROUND: This study reports two cases of undeclared and unusual foreign body (FB) impaction in the ears of Nigerian adult patients that were accidentally discovered and successfully managed. AIM: The report aims to create awareness, and encourage Otorhinolaryngologist to have proper otoscopy done for all patients with suspected ear FB and double check again following FBs removal. CONCLUSION It has recommended a need for an increased public enlightenment to raise awareness about the danger of cleaning the ears with cotton swab or other sharp materials. PMID- 26353431 TI - PERSISTENT CATATONIA IN A PREGNANT NIGERIAN WOMAN: A CASE REPORT. AB - BACKGROUND: The syndrome of catatonia appears to exist with many conditions, yet goes undetected by the skillful eyes of clinicians. This case which is rarely reported in literatures shows the effectiveness of antipsychotic augmenting in a persistent catatonic schizophrenia disorder. METHOD: This is a case narration of persistent catatonia in a 24-years old pregnant Nigerian woman with schizophrenia disorder. RESULTS: First line management with benzodiazepines and electroconvulsive therapy (ECT) failed to resolve the syndrome which later responded to Electroconvulsive Therapy with low dose antipsychotic augmentation. CONCLUSIONS: Cautious augmenting of electroconvulsive therapy with neuroleptics may be a quick and relatively safe procedure in the relief of schizophrenia with catatonia in pregnancy. PMID- 26353433 TI - The Vision Thing. PMID- 26353432 TI - A CASE OF PICA FOLLOWING A PARAMILITARY PRE-EMPLOYMENT ORIENTATION CAMP. AB - BACKGROUND: Pica is an unusual craving for and ingestion of either edible or inedible substances first observed in pregnant women but has been reported in all groups of people. Pica poses a significant health risk that often requires medical attention but the awareness of pica among physicians seems to be have reduced. METHOD: We report a case study of a young lady who presented with anaemia (pcv = 21%) and craving for sand. Laboratory investigations carried outwere in keepingwith iron deficiency anaemia. CONCLUSION: It is therefore postulated that pica may actually be a sign of iron deficiency anaemia. PMID- 26353434 TI - The Prehistory of Serendipity, from Bacon to Walpole. AB - During the past four decades there has developed a burgeoning literature on the concept of serendipity, the name for sudden insights or conceptual breakthroughs that occur by chance or accident. Studies repeatedly note that it was Horace Walpole, the eighteenth-century man of letters, who coined the word. None of them, however, notice that Walpole's term is itself indebted to a much older tradition, invoking a formula developed by Francis Bacon. Recovering the prehistory of the term suggests that "serendipity," rather than being a name for a special mode of discovery invented by Walpole, has all along accompanied empiricism as the name for an essential gap in its epistemology. Serendipity bears directly on the "induction problem," or what has more recently been called the "conceptual leap." Though Walpole gave it its current name, versions of the concept have all along isolated a critical gap in the method of the sciences inaugurated by Bacon. PMID- 26353435 TI - Building Networks for Science: Conflict and Cooperation in Nineteenth-Century Global Marine Studies. AB - In the nineteenth-century globalizing world of colonial expansion and maritime trade, systematic study of ocean currents and winds became of increased concern in various seafaring nations. Both naval officers and university professors engaged in maritime meteorological and hydrographic research. In order to attract the attention of the state and obtain support for establishment of national scientific institutes, university professors teamed up with naval officers in building networks for maritime data collection, thus connecting practical utility to academic credentials. This paper looks into the combined efforts of the U.S. Navy lieutenant M. F. Maury and the Dutch naval officer M. H. Jansen in organizing the 1853 International Maritime Conference in Brussels, which aimed to develop a worldwide system of uniform atmospheric and marine observations. Such efforts, however, amounted to walking a tightrope between mutual interests and personal rivalries. The alliance between elite scientists and naval officers proved to be only temporary. Once the meteorological institutes were established, academically trained meteorologists gradually marginalized the role of naval officers in scientific research at the institutes, thereby establishing and securing their authority in maritime science. PMID- 26353436 TI - A Drifting Concept for an Unruly Menace: A History of Psychopathy in Germany. AB - The term "psychopath" has enjoyed wide currency both in popular culture and among specialists in forensic psychiatry. Historians, however, have generally neglected the subject. This essay examines the history of psychopathy in the country that first coined the term, developed the concept, and debated its treatment: Germany. While the notion can be traced to nineteenth-century psychiatric ideas about abnormal, yet not completely pathological, character traits, the figure of the psychopath emerged out of distinctly twentieth-century preoccupations and institutions. The vagueness and plasticity of the diagnosis of psychopathy proved to be one of the keys to its success, as it was embraced and employed by clinicians, researchers, and the mass media, despite attempts by some to curb its use. Within the span of a few decades, the image of the psychopath became one of a perpetual troublemaker, an individual who could not be managed within any institutional setting. By midcentury, psychopaths were no longer seen as simply nosological curiosities; rather, they were spatial problems, individuals whose defiance of institutional routine and attempts at social redemption stood in for an attributed mental status. The history of psychopathy therefore reveals how public dangers and risks can be shaped and defined by institutional limitations. PMID- 26353438 TI - Introduction: The Humanities and the Sciences. AB - The humanities and the sciences have a strongly connected history, yet their histories continue to be written separately. Although the scope of the history of science has undergone a tremendous broadening during the past few decades, scholars of the history of the humanities and the history of science still seem to belong to two separate cultures that have endured through the past century. This Focus section explores what common ground would enable a study of the histories of the humanities and the sciences to investigate their shared epistemic objects, virtues, values, methods, and practices. PMID- 26353437 TI - The Invisible and Indeterminable Value of Ecology: From Malaria Control to Ecological Research in the American South. AB - This essay tells the story of the Emory University Field Station, a malaria research station in southwest Georgia that operated from 1939 to 1958. Using the tools of environmental history and the history of science, it examines the station's founding, its fieldwork, and its place within the broader history of malaria control, eradication, and research. A joint effort of Emory University, the U.S. Public Health Service, and the Communicable Disease Center (CDC), this station was closely aligned with a broader movement of ideas about tropical diseases across the globe, but it also offers a case study of how science in the field can veer from mainstream thinking and official policy. As the CDC and other disease-fighting organizations were moving toward a global strategy of malaria eradication through the use of DDT, the Emory Field Station developed a postsanitarian approach to malaria. Drawing on resistance among American conservationists to environmental transformation in the name of malaria control, the station's staff embraced the science and worldview of ecology in an effort to lighten public health's hand on the land and to link human health to the environment in innovative, if sometimes opaque, ways. This essay, then, argues that the Emory Field Station represents an early confluence of ecology with the biomedical sciences, something very similar to what is now the important discipline of disease ecology. PMID- 26353439 TI - A Diversity of Divisions: Tracing the History of the Demarcation between the Sciences and the Humanities. AB - Throughout history, divides between the sciences and the humanities have been drawn in many different ways. This essay shows that the notion of a divide became more urgent and pronounced in the second half of the nineteenth century. While this shift has several causes, the essay focuses on the rise of the social sciences, which is interpreted as posing a profound challenge to the established disciplines of the study of humankind. This is demonstrated by zooming in on linguistics, one of the key traditional disciplines of the humanities. Through the assumption of a correspondence between mental and linguistic categories, psychology became of central importance in the various conceptions of linguistics that emerged in the nineteenth century. Both linguistics and psychology were very much engaged in a process of discipline formation, and opinions about the proper directions of the fields varied considerably. Debates on these issues catalyzed the construction of more radical divisions between the sciences and the humanities. Both Wilhelm Dilthey's dichotomy between understanding and explanation and Wilhelm Windelband's dichotomy between nomothetic and idiographic sciences respond to these debates. While their constructions are often lumped together, the essay shows that they actually meant very different things and have to be treated accordingly. PMID- 26353440 TI - A Third Note: Helmholtz, Palestrina, and the Early History of Musicology. AB - This contribution focuses on Hermann von Helmholtz's work on Renaissance composer Giovanni Pierluigi da Palestrina. Helmholtz used his scientific concept of distortion to analyze this music and, reversely, to find corroboration for the concept in his musical analyses. In this, his work interlocked with nineteenth century aesthetic and scholarly ideals. His eagerness to use the latest products of historical scholarship in early music reveals a specific view of music history. Historical documents of music provide the opportunity for the discovery of new experimental research topics and thereby also reveal insights into hearing under different conditions. The essay argues that this work occupies a peculiar position in the history of musicology; it falls under the header of "systematic musicology," which eventually emerged as a discipline of musicology at the end of the nineteenth century. That this discipline has a history at all is easily overlooked, as many of its contributors were scientists with an interest in music. A history of musicology therefore must consider at least the following two caveats: parts of it take place outside the institutionalized field of musicology, and any history of musicology must, in the last instance, be embedded in a history of music. PMID- 26353441 TI - A Comparative Framework for Studying the Histories of the Humanities and Science. AB - While the humanities and the sciences have a closely connected history, there are no general histories that bring the two fields together on an equal footing. This paper argues that there is a level at which some humanistic and scientific disciplines can be brought under a common denominator and compared. This is at the level of underlying methods, especially at the level of formalisms and rule systems used by different disciplines. The essay formally compares linguistics and computer science by noting that the same grammar formalism was used in the 1950s for describing both human and. programming languages. Additionally, it examines the influence of philology on molecular biology, and vice versa, by recognizing that the tree-formalism and rule system used for text reconstruction was also employed in DNA genetics. It also shows that rule systems for source criticism in history are used in forensic science, evidence-based medicine, and jurisprudence. This paper thus opens up a new comparative approach within which the histories of the humanities and the sciences can be examined on a common level. PMID- 26353442 TI - History of Science and History of Philologies. AB - While both the sciences and the humanities, as currently defined, may be too heterogeneous to be encompassed within a unified historical framework, there is good reason to believe that the history of science and the history of philologies both have much to gain by joining forces. This collaboration has already yielded striking results in the case of the history of science and humanist learning in early modern Europe. This essay argues that first, philology and at least some of the sciences (e.g., astronomy) remained intertwined in consequential ways well into the modern period in Western cultures; and second, widening the scope of inquiry to include other philological traditions in non-Western cultures offers rich possibilities for a comparative history of learned practices. The focus on practices is key; by shifting the emphasis from what is studied to how it is studied, deep commonalities emerge among disciplines--and intellectual traditions -now classified as disparate. PMID- 26353443 TI - David C Lindberg, 1935-2015. PMID- 26353444 TI - [Historiae]. PMID- 26353445 TI - [Congenital hypomyelination in a Japanese boy]. PMID- 26353446 TI - [Primary cilia and hedgehog signaling]. AB - The primary cilium is an immotile organelle protruding from the cell surface in almost all vertebrate cells. Many molecules inside the primary cilia coordinately play a pivotal role, so genetic defects of these components result in diverse congenital malformations of the brain, eye, liver, kidney, and skeleton. Hedgehog signaling is a highly conserved pathway regulating morphogenesis in early development and tumorigenesis postnatally. Recently, advanced molecular biology has revealed that components of hedgehog signaling such as PTCH1, SMO, and GLI specifically translocate within the primary cilium upon the ligand binding of the hedgehog protein, and transduce the biological growth signal from the cell surface to the nucleus. Haploinsufficiency of the components in the primary cilium would inhibit the hedgehog pathway, resulting in developmental anomalies like ventral neural tube defects. Since the hedgehog-dependent pathway is critical for vertebrate development, it is crucial to elucidate the functional roles of hedgehog-related proteins in the primary cilium. PMID- 26353447 TI - [Update of steroid therapy for Duchenne muscular dystrophy]. AB - Several novel therapies for Duchenne muscular dystrophy (DMD) have recently been developed. However, steroids are currently the only medication that has been objectively confirmed to have an effect on muscle weakness in DMD patients. Prednisolone has recently been approved for pharmaceutical use in DMD patients in Japan. Moreover, the domestic guidelines for DMD have been published, which may lead to an increase in the use of steroid therapy. The short-term effects of steroid therapy for improving motor function have already been confirmed. Subsequently, the long-term effects of steroid therapy, such as prolonging the time until loss of walking ability, delay of scoliosis, and preservation of cardio-pulmonary function, have also been recognized. However, the long-term side effects, such as obesity and bone demineralization, remain a concern. Several clinical studies are currently ongoing, worldwide, to develop an optimal regimen of steroid therapy. PMID- 26353448 TI - [Effectiveness and safety of long-term levetiracetam treatment in patients with refractory epilepsy]. AB - OBJECTIVE: To evaluate the long-term effects and tolerability of levetiracetam (LEV) in refractory epilepsy. METHODS: LEV was administered to 76 patients whose seizures were inadequately controlled by their current medications. The patients were followed for a minimum of 18 months but less than 2 years. The efficacy of LEV treatment was assessed retrospectively as the proportion of patients who experienced at least a 50% reduction in the frequency of seizures (50% RR), and adverse events were analyzed. RESULTS: The 50% RR in all 76 patients was 42%. The 50% RRs in the 54 patients with localization-related epilepsy and in the 20 patients with generalized epilepsy were 42% and 35%, respectively. The patients who responded most remarkably to the therapy, with at least a 75% reduction in the frequency of seizures, were more often those with localization-related epilepsy. Among adverse events, irritability and hyperactivity/impulsivity were observed more frequently in this study than in previous reports. These events were observed predominantly in patients suffering from autism or attention deficit hyperactivity disorder (AD/HD) as a comorbidity. gamma-GTP values were improved in 14 of 17 patients whose values prior to beginning LEV treatment were higher than the normal range. This beneficial effect presumably resulted from a dose reduction or the discontinuation of other hepatotoxic antiepileptic drugs. CONCLUSIONS: LEV was useful for the treatment of refractory epilepsy, and long term efficacy was demonstrated. LEV also appeared to be less hepatotoxic. Behavioral changes should be monitored carefully when LEV is administered to patients with concomitant autism or AD/HD. PMID- 26353449 TI - [Academic achievement of children born with very low birth weights at the age of 10 years]. AB - OBJECTIVE: The academic achievement in Japanese and arithmetic of children born with very low birth weights (VLBW) was examined by means of academic skill tests at the age of 10 years. METHODS: The participants were 14 VLBW children who could be followed up in our hospital at the age of 10 years, and 6 men and 8 women. They had a mean gestational age of 27 weeks and 6 days and a mean birth weight of 988 g. The tests of the fourth grade of Japanese and arithmetic were performed during the waiting time of outpatient. The results were compared with those in typical development (TD) children. RESULTS: Concerning the comprehension of Japanese, the correct answer rate as to the problems answered in their own word was 42.9 +/- 51.4% in the VLBW children and 69.7 +/- 46.3% in the TD children, respectively. The correct answer rate as to composition was 28.6 +/- 46.9% in the VLBW children and 72.7 +/- 44.9% in the TD children, respectively, that in the VLBW children being obviously low. The correct answer rate as to calculation laws of arithmetic was 55.4 +/- 14.7% in the VLBW children and 66.3 +/- 15.5% in the TD children, respectively. The sentence resolving as to arithmetic was 42.9 +/- 50.4% in the VLBW children and 52.9 +/- 50.1% in the TD children, respectively. CONCLUSIONS: The VLBW children had difficulty in Japanese and arithmetic which required the sentence understanding, compared with the TD children. PMID- 26353451 TI - [Study of lamotrigine efficacy on behavior disorders affecting patients with severe mental retardation]. AB - OBJECTIVE: We studied the effect of lamotrigine (LTG) in children/adults with severe mental retardation and behavioral problems. METHODS: We studied 10 cases with the following conditions: (1) severe or profound mental retardation, (2) various behavioral problems and troubles in daily life, (3) insufficient effects or side effects from antipsychotic drugs, (4) ongoing epileptic seizures or EEG indications of epilepsy, (5) no previous LTG administration, (6) the ability to provide informed consent. We began administering small doses and increased to a maximum dose of LTG in 50 mg/day. We determined the improvement of behavioral problems based on family and patient interviews or our medical examinations. RESULTS: Treatment (still ongoing) has resulted in 7 of the 10 cases showing effects of LTG. Also, 2 of the remaining 3 cases have discontinued medication due to evident changes of mood. Eight cases have showed effects with doses of 10 mg or less per day. We encountered one adult subject who seems to have realized the neuropsychological effect on recognition impairment. We speculated that this patient came to read other people's emotional changes and expected to be either criticized or directed. CONCLUSIONS: Small doses of LTG appear to improve behavioral problems in children/adults with severe mental retardation. PMID- 26353450 TI - [Parenting resilience for rearing a child with autism spectrum disorder: a qualitative study]. AB - OBJECTIVE: Resilience is defined as the dynamic process of positive adaptation despite the experience of adversity. The aims of this study were to apply the concept of resilience to the mothers of children with autism spectrum disorder (ASD), which we call "parenting resilience" for rearing a child with ASD, and to explain the construct of parenting resilience. METHODS: Interviews were conducted with 23 mothers of adults with ASD to collect data on rearing these children from infancy to adulthood. Data were analyzed using a modified grounded-theory approach. RESULTS: The analytic theme was the thought process from the problems associated with raising developmentally challenged children to the implementation of the appropriate coping method. We proposed a model comprising twelve concepts and five categories, i. e., "a sense of motherhood", "self-efficacy", "knowledge of the child's characteristics", "perceived social support", and "foresight". The model assumes that a sense of motherhood and self-efficacy motivate these mothers to cope with the problems associated with developmentally challenged children, and they derive the way of dealing with it from knowledge of the child's characteristics, perceived social support, and foresight. DISCUSSION: We suggest that the construct of parenting resilience for rearing a child with ASD is composed of the proposed categories and concepts. PMID- 26353452 TI - [Analysis of factors related to social functioning in school students with high functioning pervasive developmental disorder]. AB - OBJECTIVE: To analyze the factors related to social functioning in school students with high-functioning pervasive developmental disorder (HFPDD), we investigated speech delay in infancy, family history of pervasive developmental disorder (PDD), intelligence quotient (IQ), strength of PDD characteristics, age, age at diagnosis of PDD, and social adaptive functioning in students with HFPDD. METHODS: Fifty-eight students with a diagnosis of HFPDD (IQ >= 85) were evaluated retrospectively. PDD characteristics were measured by the Pervasive Developmental Disorders Autism Society Japan Rating Scale (PARS), IQ was measured by the Wechsler Intelligence Scale for Children-Third Edition (WISC-III), and social adaptive functioning was measured by the Children's Global Assessment Scale (CGAS). RESULTS: There was a negative correlation between age at diagnosis of PDD and the CGAS score. None of the other factors examined had any significant correlation with social functioning in students with HFPDD. Age at diagnosis of PDD whose social functioning was good was significantly low. CONCLUSIONS: School students with HFPDD who are diagnosed with PDD earlier exhibit better social adaptive functioning. PMID- 26353453 TI - [High sensitivity to cell death and low repair activity of DNA damages after exposure to oxidative stress in Cockayne syndrome (CS) patient-derived cells]. AB - OBJECTIVE: To investigate the protective function of Cockayne syndrome (CS) patient-derived cells against oxidative stress, we examined the sensitivity to cell death and the repair activity of DNA damages after exposure to oxidative stress in CS cells. METHODS: We used two CS cell lines, CS3BES (CSA defective) and CSIANS (CSB defective), the human cervical cancer cell line HeLa cells, and the human fibroblastic cell line RSa. Cells were exposed to oxidative stresses, such as X-ray irradiation and hydrogen peroxide treatment, and the sensitivity to cell death was examined using the colony survival assay and MTT assay. DNA lesions were analyzed using the comet assay. RESULTS: CS3BES and CS1ANS cells showed higher sensitivity to cell death induced by X ray and hydrogen peroxide than HeLa and RSa cells. Furthermore, after exposure to the stresses the levels of DNA damage were higher, or repair activity was lower in CS3BES cells when compared with HeLa cells. CONCLUSIONS: The present results clearly show that the two CS cell lines are vulnerable to oxidative stress and suggest that both CSA and CSB proteins are involved in the protective response against oxidative injury. PMID- 26353454 TI - [A patient with an early diagnosis of PCDH19-related epilepsy]. AB - An abnormality in PCDH19 causes intractable early-onset epilepsy limited to females, and its significance in pediatric epilepsy is currently increasing. We report the case of a girl with an early diagnosis of PCDH19-related epilepsy. Focal seizures, consisting of eye deviation and asymmetrical tonic posturing, first appeared in clusters at the age of 5 months. Although each seizure was brief (less than a few minutes), seizures occurred in clusters. Cluster was observed at ages of 7, 10, 11, 14, and 19 months, respectively, and all were intractable to multiple treatments. Each cluster continued for 3 days to 2 weeks. However, no seizures occurred outsides the clusters. The pattern of seizure occurrences was characteristic of PCDH19-related epilepsy, which we first suspected when the patient was 11 months old. Genetic analysis of PCDH19 revealed two novel missense substitutions: c.1294G>=C (p.D417H) and c.1786G>=T (p.D596Y). Her psychomotor development was normal at the last follow-up at age of 1 year and 9 months. Currently, the pathogenesis and best treatments of PCDH19-related epilepsy remain unclear. However, to provide correct diagnosis and genetic counseling, and to avoid overtreatments, the possibility of this disease should be considered early in girls with intractable seizure clusters which starting during infancy to early childhood. PMID- 26353455 TI - [Efficacy of topiramate for intractable epileptic spasms in children with symptomatic epilepsy]. PMID- 26353457 TI - [Jose Tiburcio Borda]. PMID- 26353458 TI - [Infrequent complication of severe pancreatitis]. PMID- 26353459 TI - [Abdominal multilocular cystic lesion]. PMID- 26353460 TI - [Hepatitis C patients' record in the Sentinel Units for viral Hepatitis in Argentina 2007- 2014. Distribution by year of birth]. AB - Recommendations for Hepatitis C screening based on risk factorsfor transmission proved to be ineffcient. Accordingly, the CDC recommended to screen all American individuals born between 1945-1965, based on data from population prevalence of infection. The effectiveness of implementing these recommendations in other contexts and/or populations can be estimated, in principle, knowing the age distribution of infected individuals. There is no data on population prevalence in our country. Yet we can know the age distribution of cases of Hepatitis C who accessed the health system. The aim of this paper is to analyze the distribution by birth cohort ofcases registered as "Hepatitis C" in the Sentinel Units for Viral Hepatitis in the 2007-2014 period. This will contribute to the identification, if any, ofa cohort in which case the recommendation of screening could be addressed, based on risk factors inherent to our country and our epidemiological reality. The age distribution of our cases was wider and younger than those of the population supporting the recommendation of the CDC and this suggests -beyond the difference in the populations being compared- is due to a range of risk factors and age at different infection between USA and Argentina. Thus, based on these results, the recommendation of the Argentine Consensus for Hepatitis C in 2013 to screen all individuals once in life is supported. PMID- 26353461 TI - [Radiofrequency ablation for Barrett's esophagus. Preliminary experience]. AB - Endoscopic radiofrequency ablation makes use of warm energy to ablate the esophagus's surface where the epithelial anomaly is located. PATIENTS AND METHODS: 50 adults patients with the diagnosis of EB according to Vienna Classification were included. OBJECTIVES: To evaluate the security and efficacy of ARF in patients with EB. RESULTS: 50 ARF treated patients were included with a medium follow up of 18 months. The median age was 58 years. 1.4 sessions of ARF perpatient were made to obtain EB erradication. The procedure morbidity was 6%, the more frequent complication was the esophageal stenosis (two cases). During the follow up, intestinal metaplasia recurrence was not observed. CONCLUSIONS: In the experience of our team, ARF is a secure procedure with low morbidity. These observations added to the published results help to evaluate the currentfollow up protocols. PMID- 26353462 TI - [Evaluation of knowledge about colon cancer prevention versus other tumors]. AB - In Argentina almost 7% of deaths are due to different cancers with screening strategies. OBJECTIVES: Evaluate knowledge about cancer prevention compared with other tumors. Materials. A descriptive and comparative study. A survey between April and June 2013 in Salta City, province of Salta, Argentina. Correct answers were considered. Statistical analysis: Descriptive (mean and percentage), comparative Chi square Test (significance level P<0,05). RESULTS: 100 surveys. Correct answers: 36% Colon (CI 0,27-0,45), 46% Prostate (CI 0,33-0,52) and 69 (CI 0,59-0,77) and 58 (CI 0,48-0,67)for mama and cervix. 20% (CI 0,13-0,28) knew that colon cancer has a genetic predisposition and 58% (CI 0,48-0,67) about mama. 73% (CI 0,63-0,8) received information about cancer prevention. The main source of information was the physician. 46% (CI 0,36-0,55) received medical care in private institutions. Those who had social security, higher educational levels and medical care in private institutions had better knowledge about cancer prevention except in colon cancer. CONCLUSIONS: The global results showed levels below 70% in general but extremely low in colon cancer. Not having social security, receiving medical care in public institutions and having a low educational level are related with poor knowledge about cancer prevention except for colon and prostate cancer. PMID- 26353463 TI - [Gastrointestinal obstruction in the mosaic trisomy X]. AB - Trisomic X is a sex chromosomal abnormality that may be presented in mosaic. This is not extremely rare, the majority of cases go undiagnosed. The prevalence has been established to 1/1000 females. It is clinically characterized by tall stature, microcephaly, hypertelorism, congenital abnormalities, and motor and language delays. The association between the trisomic X and gastrointestinal malformations is extremely rare. We report a case of mosaic trisomic X with gastric obstruction expanding the clinical spectrum of this entity and emphasizing its unknown pathogenesis. PMID- 26353464 TI - [Hemobilia secondary to hepatic artery pseudoaneurysm]. AB - Hemobilia is defined as the presence of blood in the biliary tree characterized by the triad: jaundice, right hypochondrium pain (RH) and upper gastrointestinal bleeding (UGB). Among the etiologies highlighted in order of frequency there are: liver trauma (accidental and iatrogenic), inflammatory causes (acute and chronic cholecystitis), infections (cholangitis, liver abscesses, parasitic infections) and vascular diseases (aneurysms, vasculitis, arteriovenous malformations). There exist many complementary tests for the diagnosis of hemobilia, such as imaging (abdominal ultrasound, CT scan, angio CT), videoendoscopy, endoscopic retrograde cholangiopancreatography and angiography, the latter being considered the diagnostic tool and therapeutic modality of choice. We report the case of a 52 year-old male patient with hemobilia secondary to apseudoaneurysm ofthe hepatic artery, along with a review of the existing literature. PMID- 26353465 TI - [Mesenteric panniculitis as the initial manifestation of a B cell lymphoma]. AB - Mesenteric panniculitis is an uncommon clinical entity which sometimes may be associated with hematologic, gastrointestinal and urological neoplasms. The diagnostic procedure ofchoice is based on obtaining a tissue sample for histopathological study usually through apercutaneous procedure. Treatment is indicated in symptomatic cases. PMID- 26353466 TI - [Colonic Lipomatosis: report of a case and review of the literature]. AB - Colonic lipomas are a rare entity, even lessfrequent colonic lipomatosis (lipohyperplasia) of which we only found very few reports in literature (five cases). We report a case of colonic lipomatosis in a young adult that manifested as acute diverticulitis with perforation and rectalpolyposis requiring surgical resolution. PMID- 26353467 TI - [Gastric Bypass versus Sleeve gastrectomy: comparison between type 2 Diabetes weight loss and complications. Review of randomized control trails]. AB - INTRODUCTION: Obesity today is a major health problem worldwide and the leading health problem in Western countries because it is associated with multiple comorbidities that increase the mortality of these patients. MATERIAL AND METHODS: A review of the literature was done in PubMed (Medline) and Cochrane Library of randomized controlled trials comparing gastric bypass with sleeve gastrectomy in the treatment of obesity and type 2 diabetes mellitus (T2DM). Eighteen papers were found, of which eleven met the initial inclusion criteria. DISCUSSION: The variables analyzed to determine the superiority of one technique over the other were: the percentage ofexcess BMI lost (% EIMCP), the percentage of excess weight loss (% EPP), BMI at the end of the study, lost Kg and the percentage of weight lost. Regarding the control of T2DM fasting glycemia, the glycosylated hemoglobin (HbAlc), whether or not oral agents or insulin were considered. CONCLUSION: No highlighting differences in results that can be obtained with RYGB and MG to control obesity and T2DM. Either method achieves excellent results, even surpassing those obtained with dietary, pharmacological and behavioral treatment. PMID- 26353468 TI - Pancreatic polypeptide: a review of its involvement in neuro-endocrine reflexes, islet-acinar interactions and ethanol-evoked physiopatologic pancreatic gland changes. AB - prevents, in pancreocytes, the evolving of a "supramaximalecbolic-stimulation" process. The PP involvement as a modulating agent of pancreon's reactivity is reflected by the progressive increment of its plasma values in the first week of an evolving AP episode. In the AP associated to a large meal, an overpowering of the pancreon's brake might have a pivotal role. In experimental and clinical chronic alcoholism, a vagal neuropathy of the Pavlov inhibitory fibers that, as a consequence, impairs the pancreon's brake through a depression of PP secretion is at the basis of an enhanced reactivity of the duodeno-pancreatic reflexes. The latter leads to intrapancreatic cholinergic hypertonus and to Vater papilla's dysfunction. These changes, plus an enhanced pancreocyte's response to CCK, are at the core of acinar cell "supramaximal stimulation" with the organelle disruption that process implies. The intrapancreatic cholinergic hypertonus, the enhanced exocrine cell reactivity to CCK stimulation, and the augmented resistance to the pancreatic secretion flow at Oddi sphincter, explain the aggravating influence of chronic alcoholism on an episode of acute biliary pancreatitis. As the PP secretion, normally elicited by secretin, CCK, food and insulin hypoglycemia, is depressed in the presence of an augmented number of PP cells, as it is in the cases of chronic alcoholics, cystic fibrosis patients and, also, in dogs with pancreatic fibrosis (ductal ligation), it has been inferred, besides our postulated impairment of the Pavlov inhibitory fibers in the vagus nerves, that the defect of PP release is localized to the common final pathway of the above stimuli, probably in or near the PP cell itself This review was prompted by the unexpected experimental finding in canines that Tissucol-induced pancreatic ductal blockade elicits Pancreatic Polypeptide (PP) release and seems to be at the basis of the beneficial effects on taurocho- late-induced acute pancreatitis (AP). In the release mechanism of this regulatory peptide secreted by PP cells located in the periphery of Langerhans islets and scattered in the ductal epithelium, two neuroendocrine reflexes (NER) are involved. The "short" NER is evoked from the duodenum by an unknown component of bile-pancreatic secretion. The "long" NER is triggered by a vagovagal reflex. PP induces a depression of the intrapancreatic cholinergic tone. On the one hand suppressing, hormonally, nervous impulses discharge from the vagal nuclear complex in the brainstem. On the other, interfering paracrinically on the cholinergic transmission by acting, presynaptically, on post-ganglionic cholinergic neurons. The resulting PP-evoked fall of the intrapancreatic cholinergic tone depresses the hormone induced (secretin, CCK) pancreons secretory response. PP, with other agents, contributes to the "fail-safe" system or pancreon's brake that PMID- 26353470 TI - Breathable Medicine: Pulmonary Mode of Drug Delivery. AB - Pharmaceutically active compounds require different modes of drug delivery systems to accomplish therapeutic activity without loss of its activity and lead to exhibit no adverse effects. Originating from ancient days, pulmonary mode of drug delivery is gaining much importance compared to other modes of drug delivery systems with respect to specific diseases. Pulmonary drug delivery is a non invasive route for local and systemic therapies together with more patient convenience, compliance and is a needleless system. In this review, we addressed the vaccine delivery via non- or minimally invasive routes. Polymeric nanoparticles are preferred for use in the pulmonary delivery devices owing to a prolonged retention in lungs. Small site for absorption, mucociliary clearance, short residence time and low bioavailability are some of the limitations in pulmonary drug delivery have been resolved by generating micro- and nano-sized aerosol particles. We have classified the breathable medicine on the basis of available devices for inhalation and also prominent diseases treated through pulmonary mode of drug delivery. Owing to increasing toxicity of pharmacological drugs, the use of natural medicines has been rapidly gaining importance recently. The review article describes breathability of medicines or the pulmonary mode of drug delivery system and their drug release profile, absorption, distribution and efficacy to cure asthma and diabetes. PMID- 26353471 TI - Stem Cell Labeling with Superparamagnetic Iron Oxide Nanoparticles Using Focused Ultrasound and Magnetic Resonance Imaging Tracking. AB - Magnetosonoporation (MSP) is a relatively safe and efficient approach for instant MR stem cell labeling. In this study, the physical and magnetic properties of different formulations of synthesized superparamagnetic iron oxide nanoparticles (SPION) were characterized. Then, a "closed" MSP apparatus using focused ultrasound was designed and the feasibility of MSP stem cell labeling using focused ultrasound was validated by evaluating the proliferation, migration and differentiation of the magnetically labeled cells. Subsequently, MSP/SPION labeled neural stem cells (NSCs) were transplanted into the contralateral striatum of glioma-bearing nude mice, and their migration was monitored using magnetic resonance imaging (MRI) in vivo. The results indicated that SPION-1 with the largest size (28.43 +/- 9.55 nm) had the highest T2 relaxivity (136.62 Fe mM( 1) S(-1)) and the best MRI contrast effect. Without additional transfection reagents, NSCs were labeled with SPION using focused ultrasound in vitro and the safety of MSP stem cell labeling was validated with the optimized MSP technique. Finally, confirmed by histological evaluation, pronounced signal attenuation on T2-weighted images demonstrated the intracranial tumor tropism of NSCs could be monitored non-invasively by MRI. In conclusion, MSP cell labeling using focused ultrasound is a promising technique and the "closed" device is feasible, convenient and safe for instant magnetic stem cell labeling and MRI cell tracking. PMID- 26353472 TI - Preparation of pH-Sensitive Dextran Nanoparticle for Doxorubicin Delivery. AB - One of challenge for cancer therapy is efficient delivery of anticancer agents into tumor sites to increase efficiency of drugs and reduce side effects. To overcome this challenge, we designed pH- sensitive doxorubicin prodrug (DEX-PEI DOX) nanoparticles based on dextran-poly(ethylene imine) copolymers (DEX-PEI). The DEX-PEI-DOX conjugates were conveniently prepared by grafting PEI to dextran, and then anticancer drug doxorubicin (DOX) were conjugated to DEX-PEI through acid cleavable cis-aconityl bonds. The experiments of dynamic light scattering (DLS) and transmission electron microscopy (TEM) represented that size of dextran nanoparticles was about 120 nm with uniform spherical shape. In vitro drug release from self-assembled nanoparticles was dependent on the pH of medium due to the cis-aconityl linkage. Confocal images revealed that dextran based pH sensitive DOX delivery nanoparticle could enter into Human breast carcinoma (MCF 7) cells easily. Therapeutic efficacy against MCF-7 cells in vitro was evaluated through MTT assays and the results showed that dextran nanoparticle had obvious anticancer ability. All above results indicated this pH-sensitive DOX-loaded nanoparticles system would be a useful candidate for cancer therapy. PMID- 26353473 TI - Mannosylated Chitosan Nanoparticles Based Macrophage-Targeting Gene Delivery System Enhanced Cellular Uptake and Improved Transfection Efficiency. AB - Gene transfer mediated by mannosylated chitosan (MCS) is a safe and promising approach for gene and vaccine delivery. MCS nanoparticles based gene delivery system showed high in vivo delivery efficiency and elicited strong immune responses in mice. However, little knowledge about the cell binding, transfection efficiency and intracellular trafficking of MCS nanoparticles had been acquired. In this study, using gastrin-releasing peptide as a model plasmid (pGRP), the binding of MCS/pGRP nanoparticles to macrophages and the intracellular trafficking of MCS/pGRP nanoparticles in macrophages were investigated. MCS mediated transfection efficiency in macrophages was also evaluated using pGL-3 as a reporter gene. The results showed that the binding and transfection efficiency of MCS nanoparticles in macrophages was higher than that of CS, which was attributed to the interaction between mannose ligands in MCS and mannose receptors on the surface of macrophages. Observation with a confocal laser scanning microscope indicated the cellular uptake of MCS/pGRP nanoparticles were more than that of CS/pGRP nanoparticles in macrophages. MCS/pGRP nanoparticles were taken up by macrophages and most of them were entrapped in endosomal/lysosomal compartments. After the nanoparticles escaping from endosomal/lysosomal compartments, naked pGRP entered the nucleus, and a few MCS might enter the nucleus in terms of nanoparticles. Overall, MCS has the potential to be an excellent macrophage-targeting gene delivery carrier. PMID- 26353474 TI - Optimization of Polydiacetylene-Coated Superparamagnetic Magnetite Biosensor for Colorimetric Detection of Biomarkers. AB - Biosensors for point-of-care testing of critical illnesses are urgently needed, especially in many areas of poor healthcare infrastructure. Polydiacetylene-based sensors are ideal because of their unique colorimetric properties where blue to red color shifts can be observed with the naked eye. In this work, a colorimetric biosensor capable of simple, rapid magnetic separation is optimized, using horse IgG as a model antibody, to obtain higher sensitivity. Composed of a unique combination of polydiacetylene and superparamagnetic iron oxide, the biosensor is fabricated at varying ratios of polydiacetylene to demonstrate optimization of color responsiveness. At increasing polydiacetylene ratios, improved color responsiveness and aqueous dispersion are observed, but the magnetic separation efficiency starts to suffer. The optimal color response is obtained at 90 wt% polydiacetylene. In addition, a 50 times improved lower detection limit of 0.01 mg/mL horse IgG is achieved, a relevant biomarker concentration for diagnosing sepsis. This platform provides a promising colorimetric biosensor for point-of care use. PMID- 26353475 TI - Antineoplastic Activity Comparison of Bovine Serum Albumin--Conjugated Sulfides Semiconductor Nanomaterials. AB - Although tumor is one of the most frequently occurring diseases and a leading cause of death, nanotechnology, one of the frontier sciences, is exhibiting its great potential to tumor treatments. The aim of this study was to design a facile and environmentally-friendly method to prepare bovine serum albumin-conjugated heavy metal sulfides nano-materials, including Ag2S, PbS and CdS. Here, bovine serum albumin was introduced in order to direct the synthesis of nano-materials by using its template effect and supply more sites for further modification in future. The crystal structure and morphology were analyzed by XRD and TEM, respectively. Additionally, the antineoplastic activity of nano-materials was compared by cell viability analysis, optical and electron microscopy observation after exposure of the human hepatoma cell line. The results showed that the inhibition effect of heavy metal sulfides on tumor cells was in the order of nano PbS > bulk CdS > nano-Ag2S > nano-CdS > bulk PbS > bulk Ag2S. It could be concluded that heavy metal sulfides had significantly negative impact on human hepatoma cells growth but it could not be obviously generalized that nano particles were always more effective to kill tumor cells than bulk materials. The size and surface reactivity might be the important factors causing the difference. PMID- 26353476 TI - Preparation and Characterization of Puerarin-Loaded Lipid Nanocapsules. AB - The puerarin-loaded lipid nanocapsules (PUE-LNCs), composed of labrafac, lipoid and water, were prepared with a phase inversion procedure. The formulation was optimized by simplex lattice design and characterized for its size, zeta potential and in vitro drug release. The results showed that the PUE-LNCs performed a homogeneous typical core-shell structure under transmission electron microscope (TEM). The entrapment efficiency and drug loading were 56.61 +/- 0.27% and 2.62 +/- 0.12%, respectively. In vitro drug release revealed the PUE-LNCs showed a controlled-release manner in both artificial simulated gastric juice (pH 1.0) and artificial simulated intestinal fluid (pH 6.8). Based on the aforementioned results, it should now allow a promising tuning for further applications of LNCs as a drug delivery system for puerarin. PMID- 26353477 TI - Fluorescent Pyrene Assisted Photodeprotection of 2-(2 nitrophenyl)Propyloxycarbonyl Groups on Self-Assembled Monolayers. AB - Accelerating the photodeprotection rate of photolabile protecting group is conducive to a light-directed chemical reaction, especially for the in situ synthesis of a biochip. Herein, a photosensitizer pyrene was applied to the photodeprotection of 2-(2-nitrophenyl)propyloxycarbony (NPPOC) groups on self assembled monolayers (SAMs). It was found that the addition of pyrene could largely improve photodeprotection rate, and effectively prevent molecule damage that are often encountered by the photosensitizer 2-isopropyl thioxanthone (ITX). The most likely explanation for this result is that the whole photodeprotection process involves three joint actions, including ultraviolet light irradiation, triplet energy transfer by pyrene, and singlet fluorescence irradiation from pyrene. The joint actions enable the transfer of over-absorbed energy from pyrene to protecting groups in terms of fluorescence rather than free radicals produced by ITX that are detrimental to the molecules modified on glass substrates. Pyrene dissolved in an optimized combination of mixed solvent of dimethylacetamide (DMAC), ethanol, and dioxane with a volume ratio of 1:1:1 was tested to produce a complete photodeprotection of NPPOC groups within 6 min under 365 nm ultraviolet with an intensity of 10.8 mW/cm2. Meanwhile, tens to hundreds of cycles of photodeprotection could be conducted at a high efficiency. This research will shed light on the deprotection of photolabile groups with weak ultraviolet using a fluorescent sensitizer. PMID- 26353479 TI - Preparation of V-Doped LiFePO4/C as the Optimized Cathode Material for Lithium Ion Batteries. AB - LiFe1-x,Vx,PO4/C composites were synthesized by solid state reaction. The effect of carbon coating and V doping on the performance of LiFePO4 has been systematically investigated by X-ray diffraction (XRD), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), transmission electron microscope (TEM), charge/discharge and cyclic voltammetry (CV) measurement. The results show that carbon coating and proper amount of V incorporation do not significantly change the host crystal structure of LiFePO4, while the electrochemical performance of LiFePO4 can be significantly improved. Particularly, the LiFe0.96V0.04PO4/C exhibits the best performance with a specific discharge capacity of 105.5 mA h/g at 5.0 C, 90.3 mA h/g at 10 C and 66.7 mA h/g at 30 C with stable cycle performance, which is significantly improved compared with the pure LiFePO4/C. The cyclic voltammograms result reveals that V doping could decrease the resistance of LiFePO4/C composite electrode drastically and improve its reversibility. PMID- 26353478 TI - Use of Polylactide-Co-Glycolide-Nanoparticles for Lysosomal Delivery of a Therapeutic Enzyme in Glycogenosis Type II Fibroblasts. AB - Glycogenosis type II, or Pompe Disease, is a lysosomal storage disease caused by the deficiency of acid alpha-glucosidase (GAA), leading to glycogen accumulation in muscles. A recombinant human GAA (rhGAA, Myozyme(r)) is currently used for enzyme replacement therapy. Despite its efficacy in most of patients, some of them show a diminished response to the treatment with rapidly progressive clinical deterioration, due to immuno-mediated enzyme inactivation. To demonstrate that Nanoparticles (NPs) could be profitably exploited to carry macromolecules, PLGA NPs loaded with rhGAA (GAA-NPs) were prepared by double emulsion solvent evaporation. Their surface morphology, particle size, zeta potential and biochemical activity were assessed. "Pulse and chase" experiments were made by administrating GAA-NPs on patients' fibroblasts. Biochemical activity tests showed a more efficient cellular uptake of rhGAA loaded to NPs and a more significant stability of the enzyme (up to 7 days) in vitro, if compared to the same amount of rhGAA free enzyme. This data allows to envision in vivo experiments, in significant animal models, to further characterize lysosomal enzyme loaded-NPs' efficacy and toxicity. PMID- 26353480 TI - The Impacts of Contact Etch Stop Layer Thickness and Gate Height on Channel Stress in Strained N-Metal Oxide Semiconductor Field Effect Transistors. AB - The stress induced by strain in the channel of metal oxide semiconductor field effect transistors (MOSFET) is an effective method to boost the device performance. The geometric dimensions of spacer, gate height, and the contact etch stop layer (CESL) are important factors among the feasible booster. This study utilized the mismatch of the thermal expansion coefficients of stressors to simulate the process-induced stress in the N-MOSFET. Different temperatures are applied to different region of the device to generate the required strain. The analysis was performed by well-developed finite element package. The composite spacers with variant width of inserted silicon nitride (SiO2/SiN/SiO2, ONO) were proposed and their impacts on channel stress were compared. Two aspects of the impacts of those factors on the channel stress in the longitudinal direction for N-MOSFET with variant channel length were investigated. Firstly, the channel stresses of device without CESL for different gate heights were studied. Secondly, with stress applied to CESL and ONO spacers, the induced stresses in the channel were analyzed for long/short gate length. Two conclusions were drawn from the results of simulation. The N-MOSFET device without CESL shows that the stressed spacer alone generates compressive stress and the magnitude increases along with higher gate height. The channel stress becomes tensile for device with CESL and increases when the thickness of CESL and the height of gate increase, especially for device with shorter gate length. The gate height plays more significant role in inducing channel stress compared with the thickness of CESL. The channel stress can be used to quantify the mobility of electron/hole for strained MOSFET device. Therefore, with the guideline disclosed in this study, better device performance can be expected for N-MOSFET. PMID- 26353481 TI - Self-Assembly of Unfunctionalized Nanoparticles in Crystallization of Liquid Crystal Trimers. AB - The crystallization of liquid crystal (LC) trimer-nanoparticle blends resulted in the formation of striped patterns in the crystals. The stripes were initially blurry but became sharper in the nematic LCs formed with heating. When the striped patterns began to collapse, many micron-scale colloidal particles were found out. Both the colloidal particles and stripes disappeared after an increase of 1.0-1.5 degrees C beyond the temperature at which the colloidal particles appeared. These results suggested that the stripes consisted of the colloidal particles. The distance between stripes depended on the shapes and sizes of the colloidal particles and the cooling rate during the crystallization. There were two melting peaks on the DSC chart of the LC trimer-nanoparticle blends. The two peaks corresponded to the melting of the LC trimers and the disappearance of the colloidal particles, respectively. On the basis of these data, we think that the colloidal particles are composed of hybrid structures in which LC trimers enclose the nanoparticles. The relationship between the striped patterns and the colloidal particles is discussed. PMID- 26353482 TI - Effects of Processing Parameters on Massive Production of Graphene by Jet Cavitation. AB - The massive production of graphene by jet cavitation method with high productivity is demonstrated. Effects of the critical processing parameters on the product dispersions are studied systematically. Experimental results show that high yield of graphene flakes relies on appropriate initial concentration of graphite, high jet pressure, and long treating time. By processing a large batch (10 L) of graphite dispersion for 8 h under 20 MPa in the jet cavitation device, an exfoliation fraction of up to ~12 wt% was achieved. Based on statistical analysis of atomic force microscopy, the as-produced graphene flakes were proved to be highly exfoliated, while the distributions of flake thickness and area became narrower with the increase of treating time. Raman spectra confirm that few defects on the graphene basal planes were induced. In general, the presented approach shows advantages in comparison with peer liquid phase exfoliation methods and thus provides a new route in efficiently producing high-quality graphene in large scale. PMID- 26353483 TI - Effects of Graphene on Germination and Seedling Morphology in Rice. AB - The effects of graphene on the germination and growth of rice seeds were studied. Seeds were treated with graphene solutions at different concentrations. Obvious delaying effects on the germination rate were observed with the increasing of graphene concentration. The growth of radicle and plumule was inhibited. And also, the morphology (root length, stem length, adventitious number, root fresh weight, fresh weight of over ground part and root cap ratio) of rice seedlings was certainly affected. After been treated by different concentrations of graphene for 16 d, promoting effects on adventitious root number, root fresh weight and fresh weight of over ground part were observed at concentration of 5 mg/L. Significant inhibitions on the stem length and fresh weight of over ground part were observed at concentration of 50 mg/L. In addition, all the indexes were inhibited at concentrations of 100 mg/L and 200 mg/L. It indicates that graphene certainly inhibit the morphogenesis of rice seedlings. But the mechanism by which graphene of 5 mg/L improves part of growth indexes still needs further study. PMID- 26353484 TI - Facile Synthesis of Monodispersed Cubic and Spherical Calcite Nanoparticles in the Presence of Cetyltrimethylammonium Bromide. AB - We report the synthesis of monodisperse calcium carbonate (CaCO3) (nano)particles having either a cubic or spherical structure by reacting calcium nitrate with either sodium carbonate or citric acid, respectively, in the presence of cetyltrimethylammonium bromide (CTAB) via the sonication method. For comparison, CaCO3 (nano)particles were synthesized by the same method in the absence of CTAB and also via the standard hydrothermal method using CTAB. The synthesized CaCO3 (nano)particles were analyzed by various physico-chemical characterization techniques such as X-ray diffraction (XRD), Fourier transform infra-red spectroscopy, thermogravimetric analysis, and scanning electron microscopy with energy-dispersive spectrometer. It was found that the CaCO3 (nano)particles were highly pure with high crystallinity and exhibited the calcite polymorph phase as revealed by the XRD analysis. In addition, the analytical results showed that the (nano)particles prepared in the presence of CTAB by the sonication method had high structural ordering and no agglomeration as compared to the (nano)particles prepared by the hydrothermal method. Therefore, our sonication method is a new way to prepare shape-controlled CaCO3 (nano)particles under mild reaction conditions. PMID- 26353485 TI - A Single Pot Approach for Synthesis of Phosphate Coated Iron Oxide Nanoparticles. AB - Water dispersible Fe3O4 nanoparticles with a phosphate monolayer capping was synthesized by a single-step coprecipitation method using ferrous and ferric salt solutions, ammonia and orthophosphoric acid. The synthesized nanoparticles were characterized using thermogravimetric analyser with simultaneous differential scanning calorimetry (TGA-DSC), Fourier transform infra red spectroscopy (FTIR), X-ray diffraction (XRD), small angle X-ray scattering (SAXS), transmission electron microscopy (TEM), vibrating sample magnetometer (VSM) and dynamic light scattering (DLS). The FTIR result confirms the formation of protonated and nonprotonated monodentate complexes on nanoparticle surface. The surface coverage and the bridging of these complexes are found to be pH dependant. The DSC results confirm that the maghemite to hematite phase transition in these nanoparticles is enhanced by ~100 degrees C, which is attributed to the presence of flame retardant phosphocarbonaceous shell at the nanoparticle interface. These results show that the dynamic capping of phosphate on Fe3O4 particles during co precipitation can control the nucleated particle size, without compromising magnetic properties and improve their thermal stability. The phosphate capped Fe3O4 nanoparticles showed excellent long term stability (> 2 years of shelf life) at biological pH that makes them ideal for biomedical applications. PMID- 26353486 TI - Structure and Property of Nano-TiO2 Doped with Ag+ Membrane Photocatalyst. AB - Highly transparent silver incorporated titania (Ag/TiO2) composite nanomembranes were fabricated by a simple, reproducible dip-coating process on ceramic substrates. The obtained membrane samples were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive spectrometer (EDX), X-ray photoelectron spectroscopy (XPS). The photocatalytic activity of the Ag/TiO2 nanomembranes was assessed by the degradation of methylene blue under visible light irradiation. Compared with pure TiO2 nanomembranes, no significant shift in the TiO2 crystal structure was detected after doping with silver ions. The results from the SEM and EDX analyses showed that homogeneous spherical silver nanoparticles were produced and scattered on the surface of the TiO2 nanomembrane that was coated on the surface of the ceramic substrates. The doping with silver ions could effectively improve the photocatalytic activity of TiO2 under visible light irradiation. The Ag/TiO2 composite nanomembrane also exhibited improved hydrophilicity compared to that of a pure TiO2 nanomembrane. PMID- 26353487 TI - Development of CdS Nanostructures by Thermal Decomposition of Aminocaproic Acid Mixed Cd-Thiourea Complex Precursor: Structural, Optical and Photocatalytic Characterization. AB - The present work deals with two different CdS nanostructures produced via hydrothermal and solvothermal decompositions of aminocaproic acid (ACA)-mixed Cd thiourea complex precursor at 175 degrees C. Both nanostructures were extensively characterized for their structural, morphological and optical properties. The powder X-ray diffraction characterization showed that the two CdS nanostructures present a wurtzite morphology. Scanning electron microscopy and energy-dispersive X-ray characterizations revealed that the hydrothermal decomposition produced well-shaped CdS flowers composed of six dendritic petals, and the solvothermal decomposition produced CdS microspheres with close stoichiometric chemical composition. The UV-vis absorption and photoluminescence spectra of CdS dendritic flowers and microsphere nanostructures showed that both nanostructures present a broad absorption between 200 and 700 nm and exhibit strong green emissions at 576 and 520 nm upon excitations at 290 nm and 260 nm, respectively. The transmission electron microscopy (TEM) and Brunauer-Emmett Teller (BET) characterizations confirmed that CdS microspheres were mesoporous and were composed of small nanocrystals. A possible growth mechanism in the formation of the CdS nanostructures was proposed based on morphology evolution as a function of the reaction time. Furthermore, the as-synthesized CdS nanostructures were found to exhibit highly efficient photocatalytic activities for the degradation of methyl orange (MeO) and rhodamine B (RhB) dyes. PMID- 26353488 TI - Nanocomposite Based Organic-Inorganic Cu3BiS3 High Sensitive Hybrid Photonic Devices. AB - We report the synthesis and application Cu3BiS3 nanorods in infrared photodectection. Cu3BiS3 nano rods were characterized structurally, optically and electrically. The detailed IR photodectection properties in terms of photo response were demonstrated with IR lamp and 1064 nm laser illuminations. The rapid photocurrent time constants followed by the slower components, resulting due to the defect states. The photo detecting properties for different concentrations of nanorods blended with the conjugate polymer devices were demonstrated. Further the photocurrent was enhanced to threefold increase from 3.47 x 10(-7) A to 2.37 x 10(-3) A at 1 V for 10 mg nanorods embedded in the polymer device. Responsivity of hybrid device was enhanced from 0.0158 A/W to 102 A/W. The detailed trap assisted space charge transport properties were studied considering the different regimes. Hence Cu3BiS3 can be a promising candidate in the nano switchable near IR photodetectors. PMID- 26353489 TI - Influence of Different Reducing Agents on the Ag Nanostructures and Their Electrokinetic and Catalytic Properties. AB - This paper shows the impact of various reducing agents; sodium borohydride, trisodium citrate and polyvinyl pyrollidone (PVP) on the surface morphology of Ag nanoparticles (AgNPs). The AgNPs prepared by PVP are found to be much larger in size ca. ~ 40-70 nm having red shifted surface plasmon band (SPR band) at 475 nm as compared to relatively smaller size ~ 10-14 nm (SPR band ~ 392 nm) prepared by reduction with sodium borohydride as confirmed by both TEM and DLS analysis. PVP act as a shape-control agent and results in well defined bipyramid shaped particles while sodium borohydride and trisodium citrate yields spherical, oval and polygonal morphologies. The measured zeta potential of AgNPs prepared by sodium citrate (-28.9 mV), sodium borohydride (-20.0 mV) and PVP (-6.0 mV) is notably decreased with geometric faces. Both co-catalytic and catalytic properties of various Ag nanostructures were evaluated for the photo oxidation of benzoic acid by AgNPs-TiO2 mixture, and for the reduction of p-nitrophenol to p aminophenol, respectively. A significant increase in the catalytic (17 to 55%) and co-catalytic activity (20 to 50%) was found with decreasing size (50 to 12 nm) and increasing the surface to volume ratio (0.096 to 0.48 nm(-1)) of obtained AgNPs of different surface structure. PMID- 26353490 TI - Rapid Fabrication of Gold Nanoflowers Tuned by pH: Insights Into the Growth Mechanism. AB - We reported a one-pot, no added seeding and green method to synthesize gold nanoflowers, in which HAuC4 and H2O2 were added one by one into the alkaline protocatechuic aldehyde solution at room temperature. Au(III) was partially reduced by protocatechuic aldehyde to produce primary Au nanocrystals, and then Au nanocrystals agglomerated into loose flower-like nanoparticles as seeds, which catalyzed H2O2 reduction of the residual Au(III), thus accelerating the formation of compact 3D gold nanoflowers. The key synthesis strategy was to use protocatechuic aldehyde as a structure-induced agent to influence the growth of gold nanoflowers. The pH value of growth solution could tune the size and/or morphology of gold nanoflowers through its influence on the adhesion force of protocatechuic aldehyde on gold surfaces and the species type of Au(III) complexes. When the pH value of growth solution was above 7.26 (the pKa of protocatechuic aldehyde), the flower-like of gold nanostructural architectures with different sizes could be fabricated. The obtained gold nanoflowers had a large dimension of 198 and 157 nm at the pH of 7.6 and 8, respectively. Size control of gold nanoflowers can be accomplished in the growth solutions of pH 9.4 12.0 with a similar diameter around 60 nm. The as-synthesized gold nanoflowers exhibited good stability and have the prospects for surface-enhanced Raman scattering enhancement. PMID- 26353491 TI - Preparation and Catalytic Activities of Au/Co Bimetallic Nanoparticles for Hydrogen Generation from NaBH4 Solution. AB - A series of poly(N-vinyl-2-pyrrolidone)-protected Au/Co bimetallic nanoparticles (BNPs) were prepared by a simple route based on dropwise addition of NaBH4. Their structures, particle sizes, and chemical compositions were characterized by Ultraviolet-visible spectrophotometry, X-ray photo- electron spectroscopy, Transmission electron microscopy and High-resolution transmission electron microscopy, and their catalytic activity for the hydrogen generation from hydrolysis of an alkaline NaBH4 solution was examined. As-prepared alloy structured Au/Co BNPs had an average size between 2.8 and 3.6 nm and showed a higher catalytic activity for the hydrogen generation than the corresponding Au and Co monometallic nanoparticles (MNPs). Of all the MNPs and BNPs, Au20Co80 BNPs exhibited the highest catalytic activity, and a hydrogen generation rate of 480 mol-H2 . h(-1) . mol-M(-1) was achieved. The high catalytic activity of the BNPs can be ascribed to the formation of negatively charged Au atoms and positively charged Co atoms as a result of the electronic charge transfer effects in the BNPs. PMID- 26353492 TI - Preparation and Properties of Ethylene Vinyl Acetate Copolymer/Silica Nanocomposites in Presence of EVA-g-Acrylic Acid. AB - Here we report a facile approach to enhance the dispersibility of ethylene vinyl acetate copolymer (EVA)/silica nanocomposites (for the EVA/silica nanocomposites and interaction between silica nanoparticles (nanosilica) and EVA by adding EVA-g acrylic acid (EVAgAA) as a compatibilizer, which was formed by grafting acrylic acid onto EVA chains with the aid of dicumyl peroxide). The above nanocomposites with and without EVAgAA were prepared by melt mixing in a Haake intermixer with different contents of silica and EVAgAA. Their structure and morphology were characterized by Fourier transform infra-red (FT-IR) spectroscopy, field emission scanning electron microscopy (FE-SEM), and the mechanical, rheological, dielectrical, and flammability properties of the nanocomposites were also investigated. The FT-IR spectra of the nanocomposites confirmed the formation of hydrogen bonds between the surface silanol groups of nanosilica and C=O groups of EVA and/or EVAgAA. The presence of EVAgAA remarkably increased the intensity of hydrogen bonding between nanosilica and EVA which not only enhanced the dispersion of nanosilica in EVA matrix but also increased the mechanical, viscosity and storage modulus of EVA/silica nanocomposites. In addition, the flammability of EVA/silica nanocomposites is also significantly reduced after the functionalization with EVAgAA. However, the mechanical properties of EVA/silica nanocomposites tended to level off when its content was above 1.5 wt.%. It has also been found that the dielectric constant value of the EVA/EVAgAA/silica nanocomposites is much lower than that of the EVA/silica nanocomposites, which is another evidence of the hydrogen bonding formation between EVAgAA and nanosilica. PMID- 26353493 TI - A Physics-Based Three Dimensional Model for Write and Read Performances of Phase Change Probe Memory. AB - The write and read performances of phase-change probe memory were investigated for the first time by a physics-based pure three dimensional model. The written crystalline bit possessed from this developed model demonstrates the potential of phase-change probe memory for ultra-high density, low energy consumption, high data rate, and good readability. The cross-talk effect on the write and read performances of phase-change probe memory, which can not be modelled by previous two dimensional models, is also evaluated. The findings showed that the bit and track pitches should be remained sufficiently long so as to eliminate the undesired interferences. The simulated results exhibited a good agreement with the experimental observations, thus demonstrating the physical reality of the designed model. PMID- 26353494 TI - Nanocrystalline Pyrochlore La2Sn1.6Zr0.4 as a New Candidate for Supercapacitor Electrodes. AB - Nanocrystalline La2Sn1.6Zr0.4O7 is synthesized by microwave assisted combustion method. The phase formation and morphological features of La2Sn1.6Zr0.4O7 are characterized by X-ray diffrac- tion (XRD), X-Ray photoelectron spectroscopy (XPS), Fourier Transform Infrared (FT-IR) spectrum and Transmission Electron Microscopy (TEM) respectively. XRD pattern shows the formation of cubic Pyrochlore structure of La2Sn1.6Zr0.4O7. FTIR studies attributed the presence of characteristic functional groups of La-O, Sn-O and Zr-O. TEM image reveals that the size of La2Sn1.6Zr0.4O7 particle exhibits from 50 nm to 100 nm and the observed d-spacing from HRTEM is matched well with the XRD d-spacing. The SAED pattern shows the polycrystalline behaviour of La2Sn1.6Zr0.4O7. The room temperature electrical conductivity of La2Sn1.6Zr0.4O7 is 3.12 x 10(-6) S cm(-1). The synthe- sized La2Sn1.6Zr0.4O7 particle is explored as electrodes for supercapacitor and the performances are studied by cyclic voltammetric and charge discharge studies using 1 M H2SO4 electrolyte. From charge-discharge analysis the specific capacitance was found to be 74 Fg(-1) at 1 mA cm(-2). The resistive behaviour of the electrodes is studied through electrochemical impedance spectroscopy. Also the cycling stability is studied by performing the 100 charge discharge cycles. It reveals that there is almost 100% cycling stability is achieved. Hence nanocrystalline La2Sn1.6Zr0.4O7 pyrochlore can have the feasibility as an electrode material for supercapacitor application. PMID- 26353495 TI - Synthesis of NaYF4 and NaLuF4 Based Upconversion Nanocrystals and Comparison of Their Properties. AB - In this study, four kinds of upconversion nanocrystals (UCNs) have been successfully synthesized by a facile solvothermal method. The morphology, crystalline phase, composition, grain size, upconversion luminescence and cell image of the UCNs were investigated. The properties of the NaLuF4-based UCNs were compared with the counterparts of NaYF4-based UCNs. It is found that the NaLuF4 based UCNs are apt to form hexagonal phase structures, while NaYF4-based UCNs of NaYF4:Yb, Er and NaYF4:Gd, Yb, Er are cubic and hexagonal phases respectively. The upconversion emission intensities of the NaLuF4-based UCNs are higher than that of NaYF4-based UCNs, and Gd3+ presented UCNs are higher than that of Gd3+ absented UCNs. The bioimaging application of NaLuF4:Gd, Yb, Er shows that bright upconversion luminescence can be observed when UCNs-labeled HeLa cells are excited with 980 nm light. PMID- 26353496 TI - Bifunctional Li and Co Doped ZnO Nanostructures Synthesized by Solvothermal Method: Stabilizer Controlled Shape and Size Tuning. AB - 1D nanostructures of ZnO, Zn0.95Co0.05O and Zn0.85Co0.05Li0.10 were synthesized by a solvothermal chemical method with and without using oleic acid as a stabilizer. We report a very interesting observation of both room temperature ferromagnetism and photoluminescence properties along with development of different morphological transformation of these nanostructures on doping Co and Li in ZnO in the presence and absence of oleic acid. Zn0.95Co0.05O sample prepared in the presence of oleic acid showed increased saturation magnetization value (~ 4.1 emu/g and) compared to Zn0.95Co0.05O prepared without oleic acid (~ 1.1 emu/g). In both the cases it is observed that Li incorporation further enhances the room temperature ferromagnetic (RTFM) behavior and saturation magnetization values (~ 6 emu/g) of luminescent Zn0.95Co0.05 nanostructures. These results are significant, as the luminescent 1 D RTFM materials will have implications in photo magnetic devices like magneto-optical switches and sensors. PMID- 26353497 TI - TiO2-Based Indium Phosphide Metal-Oxide-Semiconductor Capacitor with High Capacitance Density. AB - We report a low-temperature InP p-MOS with a high capacitance density of 2.7 uF/cm2, low leakage current of 0.77 A/cm2 at 1 V and tight current distribution. The high-density and low-leakage InP MOS was achieved by using high-kappa TiLaO dielectric and ultra-thin SiO2 buffer layer with a thickness of less than 0.5 nm. The obtained EOT can be aggressively scaled down to < 1 nm through the use of stacked TiLaO/SiO2 dielectric, which has the potential for the future application of high mobility III-V CMOS devices. PMID- 26353498 TI - The Effect of Montmorillonite Clay on the Crystallinity of Poly(vinyl alcohol) Nanocomposites Obtained by Solution Intercalation and In Situ Polymerization. AB - In this study, PVAL/sodic clay nanocomposite materials were obtained using different clay ratios. The nanocomposites were prepared by solution and in situ polymerization. They were characterized through proton relaxometry and X-ray diffraction, the latter technique used to determine the crystallinity of the PVAL matrix in the nanocomposites through the addition of unmodified montmorillonite clay. The relaxation data for the nanocomposite films obtained by solution intercalation showed a decrease in the proton spin-lattice relaxation values with increased clay proportion, forming a nanostructured material with high exfoliation degree, as a result of two phenomena: the higher molecular mobility of the polymer chains around the clay layers and the presence of paramagnetic metals in the clay layers, which accelerates the hydrogen relaxation process, causing a decrease in the relaxation value. The samples obtained through in situ polymerization were mixed nanocomposites (partly exfoliated and partly intercalated). The NMR relaxation data for the systems analyzed showed the solution intercalation process was more efficient than in situ polymerization in relation to the generation of nanostructured polymers with higher degree of exfoliated clay. PMID- 26353499 TI - Surface Characteristics, Biodegradability and Biocompatibility of Porous Silicon for Microfabricated Neural Electrode. AB - Porous Si (PSi) used for microfabrication of a novel neural electrode was prepared on Si wafers by an anodization process. Surface morphology and porous structure of the PSi were characterized using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). 3D inter-connected and nano sized pores were homogeneously formed across the surface. Wettability of the PSi was determined using a sessile drop method. Although Si-Hx functional groups on the PSi surface had negative effect on wettability, water contact angle of the PSi reduced to 34.5 +/- 0.5 degrees due to the enhanced surface roughness and the capillary force generated by nano sized pores. Moreover, in vitro biocompatibility of the PSi was assessed by seeding a breast cancer cell line (MCF-7). After 5 days of culture, cell morphology was observed using a fluorescence microscope. Although more than 99% of the cells under the microscope were living for both Si and PSi samples, morphology of the cells attached on their surfaces was different. MTT assay was also used to quantitatively evaluate in vitro biocompatibility, and revealed false positive results due to the spontaneous reduction of MTT on the PSi surface. Therefore, MTT assay was not suitable for in vitro quantitatively study of PSi. PMID- 26353500 TI - Synthesis of Titanium Dioxide by Microwave Plasma Torch. AB - In this study, TiO2 nanoparticles were synthesized from titanium tetraisopropanol (TTIP) using a microwave plasma torch (MPT) and characterized by scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD) and thermogravimetry analysis (TGA). The visible light photocatalysis was studied by the decomposition of methylene blue. MB present in the aqueous solution could be almost completely (> 70%) decomposed within about 720 min of reaction time under visible light irradiation. This is due to the carbon-compounds on the surface of TiO2 (TiOC) corresponding to the results of FTIR. Furthermore, a decrease in recombination between the electron and hole was induced by the existence of TiOC. PMID- 26353501 TI - Field Emission Characteristics of Polyaniline/Se Nanocomposites. AB - Polyaniline (PAni)/Se nanocomposites have been synthesized in different compositions employing chemical route and shown excellent field emission behaviour. Detailed studies on the field emission for all composites with different concentrations of dopant are performed in an indigenously fabricated set up in a vacuum chamber with a base pressure of 10(-6) Torr at room temperature and analysed with current density versus Electric field (J-E) and Fowler-Nordheim (FN) plots. Comparative field emission results showed that 10% (w/w) doped PAni/Se nanocomposite depicts highest emission characteristics, current density and field enhancement factor with turn-on field as low as 1.2 V/um in comparison with other composites, while pure PAni shows no field emission characteristics. These composites have also been characterized by Scanning Electron Microscope (SEM) and Fourier Transform Infrared Spectrometry (FTIR). FTIR results supply the evidence for the occurrence of the polymer in its conducting state. The ease of synthesis route and interesting field emission properties recommend these composites as a promising material for field emission based applications in vacuum micro-nanoelectronic devices and also for plastic display industry. PMID- 26353502 TI - Theoretical Thermodynamics Study of Polyamidoamine Deposited Around a Nanotube as Motor Controlled by Light and Under Temperature Effect. AB - We simulated a system like a Polyamidoamine (PAMAM) deposited on open carbon nanotube. We used five first generation PAMAM. The initial position of PAMAM is out of CN symmetry position. It permits the PAMAM to relax around the nanotube due to van der Waals force. After that, we have analyzed the thermal effects on behavior of 4G PAMAM. We performed computational simulation using classical molecular dynamics with standard parameterization. The thermodynamics properties of this device as molar specific heat and molar entropy variation were calculated. The CN has 690 carbon atoms with up to almost 0.1 ns of simulation. PMID- 26353503 TI - Preparation and Microwave Absorption Properties of Novel Carbon Nanofiber/Fe3O4 Composites. AB - Novel, carbonized bacterial cellulose (CBC)/Fe3O4 nanocomposites were synthesized using vacuum filtration and annealing (VFA) methods. The as-synthesized products were characterized by scanning electron microscopy, vibrating sample magnetometry, and transmission electron microscopy. The complex permittivity and permeability of Fe3O4-CBC (5 wt.% CBC)/paraffin wax composites were measured by vector network analysis. To study the microwave absorption (MA) performances, we compared the VFA products with the vacuum filtration (VF) products. The VFA products exhibited better absorption performances because of their larger dielectric loss. When the matching thickness was 2.4 mm, the calculated reflection loss reached a minimum value of -27 dB when VFA was used and a value of -11 dB when VF was used. The wide-range MA properties of these materials lead to potential applications in MA fields. PMID- 26353505 TI - A Spray Pyrolysis Method to Grow Carbon Nanotubes on Carbon Fibres, Steel and Ceramic Bricks. AB - We demonstrate a spray pyrolysis method to grow carbon nanotubes (CNTs) with high degree of crystallinity, aspect ratio and degree of alignment on a variety of different substrates, such as conventional steel, carbon fibres (CF) and ceramics. The process consists in the chemical vapour deposition of both a thin SiO2 layer and CNTs that subsequently grow on this thin layer. After CNT growth, increases in specific surface by factors of 1000 and 30 for the steel and CF samples, respectively, are observed. CNTs growth on ceramic surfaces results in a surface resistance of 37.5 Ohm/sq. When using conventional steel as a rector tube, we observed CNTs growth rates of 0.6 g/min. Details of nanotube morphology and the growth mechanism are discussed. Since the method discussed here is highly versatile, it opens up a wide variety of applications in which specific substrates could be used in combination with CNTs. PMID- 26353504 TI - Adsorption of Phosphate in Aqueous Solution by Magnetite Modified with Diethylenetriamine. AB - A magnetic adsorbent, amine-functionalized silica magnetite (NH2-Al/SiO2/Fe3O4), has been synthesized to behave as an cationic adsorbent by adjusting the pH value of the aqueous solution to make amino groups protonated. NH2-Al/SiO2/Fe3O4 was used to adsorb phosphate ions in an aqueous solution in a batch system, and the maximum adsorption were found to occur at pH 3.0. The adsorption equilibrium data were all fitted the Langmuir isotherm equation reasonably well, and the maximum adsorption capacities of phosphate ions were more than 40 mg g(-1) and increased with elevating temperature. The enthalpy (DeltaH0) and entropy (DeltaS0) values of NH2-Al/SiO2/Fe3O4 with the adsorption reaction of phosphate ions were 11.98 KJ mol(-1) and 0.095 KJ (T mol)(-1), respectively. A pseudo-second-order model also could best describe the adsorption kinetics, and the derived activation energy for phosphate ions was 20.2 kJ mol(-1). The optimum condition to desorb phosphate ions from NH2-Al/SiO2/Fe3O4 is provided by a solution with 0.05 M NaOH. PMID- 26353506 TI - Pharmacokinetics Evaluation of Carbon Nanotubes Using FTIR Analysis and Histological Analysis. AB - Carbon nanotubes (CNTs) are biologically non-toxic and long-circulating nanostructures that have special physical properties. This study was focused on developing alternative methods that track carbon nanotubes, like FR-IR to classical tissue histological procedure. FT-IR absorption spectra were used to confirm the carboxylation of carbon nanotubes and to evaluate the presence of carbon nanotubes from bulk spleen samples and histologically prepared samples (control spleen and spleen with SWCNT-COOH). FT-IR spectrum of spleen sample from animals injected with CNTs shows major spectral differences consisting in infrared bands located at ~1173 cm(-1), ~ 1410 cm(-1); ~1658 cm(-1), ~1737 cm(-1) and around 1720 cm(-1) respectively. In terms of localization of carbon nanotubes, selective accumulation of marginal zone macrophages and splenic red pulp is observed for all treated groups, indicating the presence of carbon nanotubes even at 3, 4 and 7 days after treatment. In summary, we believe that histological evaluation and FT-IR can provide more characteristic information about the pharmacokinetcis and the clearance of carbon nanotubes. PMID- 26353507 TI - Fabrication of Superhydrophobic Surface with Controlled Wetting Property by Hierarchical Particles. AB - Hierarchical particles were prepared by synthetically joining appropriately functionalized polystyrene spheres of poly[styrene-co-(3-(4-vinylphenyl)pentane 2,4-dione)] (PS-co-PVPD) nanoparticles and poly(styrene-co-chloromethylstyrene) (PS-co-PCMS) microparticles. The coupling reaction of nucleophilic substitution of pendent beta-diketone groups with benzyl chloride was used to form the hierarchical particles. Since the polymeric nanoparticles and microparticles were synthesized by dispersion polymerization and emulsion polymerization, respectively, both the core microparticles and the surface nanoparticles can be different size and chemical composition. By means of changing the size of the PS co-PVPD surface nanoparticles, a series of hierarchical particles with different scale ratio of the micro/nano surface structure were successfully prepared. Moreover, by employing the PS-co-PVPD microparticles and PS-co-PCMS nanoparticles as building blocks, hierarchical particles with surface nanoaprticles of different composition were made. These as-prepared hierarchical particles were subsequently assembled on glass substrates to form particulate films. Contact angle measurement shows that superhydrophobic surfaces can be obtained and the contact angle of water on the hierarchically structured surface can be adjusted by the scale ratio of the micro/nano surface structure and surface chemical component of hierarchical particles. PMID- 26353508 TI - The Christaller's Formation Mechanism for the Ordered Nanopores of Anodic Alumina Template. AB - The highly ordered alumina pores were prepared via a two-step anodic oxidation process in the electrolyte of oxalic acid. Five different formation mechanisms of the alumina nanopores are summarized. On the basis of those models, combined with the Christaller's central place theory, a Christaller's formation mechanism of the alumina nanopores is proposed for the first time. It is the mechanical stresses between those pores during the corrosion expansion process that determines the morphology of alumina pores. Anodic oxidation time is too longer, the regular arrangements of pores will be damaged. This mechanism will provide the model analysis and reference value for studies of the formation mechanisms of alumina nanopores. PMID- 26353509 TI - Synthesis and Characterization of Bi2Te3 Nanostructured Thin Films. AB - Thin films of Bi2Te3 were obtained using vacuum evaporation and inert gas evaporation techniques. To study the effect of nanocrystallite size on thermal and electrical properties, deposition temperature and gas pressure were varied and thin films of Bi2Te3 having different crystallite sizes ranging from 7-20 nm were obtained. X-ray Diffraction and scanning electron microscopic studies were carried out to determine phase, crystallite size, strain and surface morphology of nanocrystalline films. Effect of nanocrystallite size on electron transport and thermal properties of Bi2Te3 thin films was studied using Hall effect and Harman's four probe methods. Calculated ZT values were correlated with the carrier concentration, carrier mobility and electrical conductivity of Bi2Te3 thin films. This study shows that strain may influence the electron transport and thermoelectric properties of Bi2Te3 films along with nanocrystallite size. PMID- 26353510 TI - Fabrication and Performance of Noble Metal Promoted Birnessite Catalysts for Complete Oxidation of Formaldehyde at Low Temperatures. AB - Noble metal (Au, Ag, Pd and Pt) promoted birnessite (Bir) catalysts were successfully prepared and tested for catalytic oxidation of formaldehyde (HCHO). The catalysts were characterized by means of X-ray diffraction (XRD), transmission electron microscopy (TEM), hydrogen temperature programmed reduction (H2-TPR), inductively coupled plasma atomic emission spectroscopy (ICP-AES) and N2 adsorption-desorption. The activities of noble metal (Au, Ag, Pd and Pt) promoted birnessite catalysts follow the order of 1.0Pt/Bir > 1.0Pd/Bir > Bir > 1.0Ag/Bir > 1.0Au/Bir, revealing that the loading of Pd and Pt improves the catalytic activity of birnessite, but the loading of Ag and Au slightly decreases the catalytic activity of birnessite. Effects of the Pt loading amount were also investigated on the activity of Pt/Bir catalysts for HCHO oxidation. Pt/Bir with a Pt loading of 1.5 wt% (1.5 Pt/Bir), which has the best reduction properties, was found to be the most efficient catalyst. Over this catalyst, HCHO could be completely oxidized into CO2 and H2O at 70 degrees . 1.5 Pt/Bir also shows good catalytic stability under the HCHO oxidation atmosphere. The differences in the catalytic activity of these materials are largely attributed to their reducibility as well as the dispersion of metal nanoparticles, but are not directly related to their specific surface areas. PMID- 26353511 TI - One-Step Synthesis of MnO2 Flower/Carbon Nanotube with Improved Lithium Storage Properties. AB - This work reports a one-step hydrothermal synthesis of MnO2-flower/Carbon nanotube (CNTs) binary material, featuring a coated-worm like structure. The material showed a specific capacity of 800 mA h g(-1), a working plateau at 0.5 V against a Li+/Li electrode, and ideal stability under a current density of 2 A g( 1). The transition of the crystalline form of MnO2 was also observed when adjusting the ratio of CNTs in the reaction, which may be an intriguing result for the material's future application. PMID- 26353512 TI - A Method for Quantitative Phase Analysis of Nanocrystalline Zirconium Dioxide Polymorphs. AB - A method based on X-ray diffractometry was developed for quantitative phase analysis of nanocrystalline zirconium dioxide polymorphs. Corresponding formulas were derived. The key factors therein were evaluated by rigorous theoretical calculation and fully verified by experimentation. A process of iteration was raised to make the experimental verification proceed in the case of lack of pure ZrO2 crystal polymorphs. By this method, the weight ratios of tetragonal ZrO2 (t ZrO2) to monoclinic ZrO2 (m-ZrO2) in any a mixture that contains nanocrystalline t-ZrO2 and m-ZrO2 or their weight fractions in a mixture that is composed of nanocrystalline t-ZrO2 and m-ZrO2 can be determined only upon an XRD test. It is proved by both theoretical calculation and experimental test that mutual substitutions of t-ZrO2 and cubic ZrO2 (c-ZrO2) in a wide range show almost no impact on the XRD patterns of their mixtures. And plus the similarity in property of t-ZrO2 and c-ZrO2, they can be treated as one whole phase. The high agreement of the theoretical and experimental results in this work also proves the validity and reliability of the theoretical calculation based on X-ray diffractometry theory for such quantitative phase analysis. This method has the potential to be popularized to other materials. PMID- 26353513 TI - Effect of Chemicals on Morphology and Luminescence of CdSe Quantum Dots. AB - CdSe quantum dots (QDs) with several morphologies were fabricated using various reaction sys- tems. In a trioctylamine (TOA) and octadecylphosphonic acid (ODPA) system, yellow-emitting (a photoluminescence (PL) peak wavelength of 583 nm) CdSe QDs revealed rod morphology and nar- row size distribution. When ODPA was replaced by tetradecylphosphonic acid (TDPA), red-emitting CdSe rods (a PL peak wavelength of 653 nm) with broad size distribution were fabricated. This is ascribed that the short carbon chain accelerated the growth of CdSe QDs. As a result, the use of ODPA resulted in CdSe QDs with high PL efficiency (3.1%). Furthermore, cubic-like CdSe QDs were created in a stearic acid (SA) and octadecene (ODE) reaction system. The PL efficiency of the QDs is low (0.2%). When hexadecylamine (HDA) was added in such SA and ODE reaction system, spherical CdSe QDs with narrow size distribution and high PL efficiency (3.4%) were prepared. PMID- 26353514 TI - Flow Type Bio-Chemical Calorimeter with Micro Differential Thermopile Sensor. AB - Bio-chemical calorimeters with a MEMS (Micro-Electro-Mechanical Systems) thermopile sensor have been studied for monitoring detailed processes of the biochemical reactions of a minute sample with a high temporal resolution. The bio calorimeters are generally divided into a batch-type and a flow-type. We developed a highly sensitive batch-type calorimeter which can detect a 100 nW level thermal reaction. However it shows a long settling time of 2 hours because of the heat capacity of a whole calorimeter. Thus, the flow-type calorimeters in passive and active mode have been studied for measuring the thermal reactions in an early stage after starting an analysis. The flow-type calorimeter consists of the MEMS differential thermopile sensor, a pair of micro channel reactor in a PDMS (polydimethylsiloxane) sheet in a three-fold thermostat chamber. The calorimeter in the passive mode was tested with dilution reactions of ethanol to water and NaCl aqueous solution to water. It was shown that the calorimeter detects exo- and endothermic reaction over 250 nW at solution flow rate of 0.05 ~ 1 ul/min with a settling time of about 4 minutes. In the active mode, a response test was conducted by using heat removal by water flow from the reactor channel. The active calorimetry enhances the response time about three to four times faster. PMID- 26353516 TI - Experimental Investigation of Thermal Performance of Miniature Heat Pipe Using SiO2-Water Nanofluids. AB - The four miniature heat pipes filled with DI water and SiO2-water nanofluids containing different volume concentrations (0.2%, 0.6% and 1.0%) are experimentally measured on the condition of air and water cooling. The wall temperature and the thermal resistance are investigated for three inclination angles. At the same of inlet heat water temperature in the heat system, it is observed that the total wall temperatures on the evaporator section are almost retaining constant by air cooling and the wall temperatures at the front end of the evaporator section are slightly reduced by water cooling. However, the wall temperatures at the condenser section using SiO2-water nanofluids are all higher than that for DI water on the two cooling conditions. As compared with the heat pipe using DI water, the decreasing of the thermal resistance in heat pipe using nanofluids is about 43.10%-74.46% by air cooling and 51.43%-72.22% by water cooling. These indicate that the utilization of SiO2-water nanofluids as working fluids enhances the performance of the miniature heat pipe. When the four miniature heat pipes are cut to examine at the end of the experiment, a thin coating on the surface of the screen mesh of the heat pipe using SiO2-water nanofluids is found. This may be one reason for reinforcing the heat transfer performance of the miniature heat pipe. PMID- 26353515 TI - Dynamic Behavior of the Liquid Flow Coalescing with a Droplet in Hydrophobic Microchannels. AB - In this study, the dynamic behavior of the moving liquid column coalescing with a sessile droplet in a hydrophobic microchannel under pressure driven flow conditions is numerically investigated using coupled Volume of Fluid with Level Set (CLSVOF) interface tracking method implemented in ANSYS-Fluent 14.5 in conjunction with the continuum surface force (CSF) model. Numerical result reveals that the coalescence between the moving liquid column and droplet can accelerate the original liquid column movement. Effects of the wettability, head pressure, and droplet size and position are also investigated. It is found that the velocity increment ratio increases with increasing the contact angle and decreasing the head pressure. Larger droplet and smaller distance between the droplet and inlet can result in a larger velocity increment ratio as a result of higher surface energy and lower viscous dissipation energy. The maximum velocity increment ratio of 0.17 is obtained with a 10000-um3 droplet that is positioned at 200 um in a microchannel with 100 um in width and 300 um in length and contact angle of 120 degrees . PMID- 26353517 TI - Raman Measurement of Heat Transfer in Suspended Individual Carbon Nanotube. AB - The excellent thermal performance of carbon nanotube (CNT) has been noticed long ago and attracted much attention. In the experiments, the electrical and thermal contact resistances remain the unsolved key problems causing undesirable measurement uncertainty. Recently, a micro-Raman spectroscopy technique has been applied to perform non-contact measurement for individual CNT, thus the contact resistances during the measurement process can be avoided. In this method, the temperature rise of CNT is a function of laser absorption probability and thermal properties, these parameters are coupled together. In this work, the thermal conductivity and optical absorption of the same CNT sample are decoupled and determined simultaneously. The thermal conductivity is obtained by measuring the temperature rise caused by a direct current heating, where the laser heating effect can be eliminated. Then the optical absorption is obtained by solving the heat transfer equation considering the thermal conductivity as a known parameter. The CNT sample is 24.8 um in length and 3 nm in diameter. The measured thermal conductivity is 2630 Wm(-1)K(-1) and the optical absorption is 0.194%. The heat transfer coefficient is evaluated using a kinetic two-layer model, which has been proven by the previous experiment. Because the length of CNT is much larger than the size of the focused laser spot, the experimental result is insensitive to the contact resistances at the ends of CNT. PMID- 26353518 TI - Efficient Mineralization of Toluene by W-Doped TiO2 Nanofibers Under Visible Light Irradiation. AB - Toxic toluene gas caused enormous harm to human health, and the traditional method to deal with this puzzle is using physical adsorption, which just transfer the toluene from one medium to another. Photocatalysis has great potential to mineralize toluene into CO2 under visible light irradiation, but their applications have been limited by difficulties in preparing efficient photocatalysts with fine crystallite size, considerable visible light response, and large surface area to contact with toluene gas. To address this problem, we have developed a film composed of W-doped TiO2 nanofibers to mineralize toluene under visible light irradiation. The electrospinning preparation route allows incorporation of up to 50 wt% of W in substitutional positions of titanium atom in the anatase network. The W-doped TiO2 nanofibers behave finer crystallite size, stronger visible light absorbance, and larger surface area comparing with pure TiO2 nanofibers. The nanofiber structured morphology on the quartz tube promotes the reaction rates for the gas-phase photo-oxidation of toluene. The concentrations of the produced CO2 keep steady during the photodegradation process, indicating the practicality and operability for the whole experiment. This research is conducive to the development of novel photocatalytic materials to efficiently mineralize toxic gas pollutants including toluene for practical application. PMID- 26353519 TI - Design, Simulation and Fabrication of Triaxial MEMS High Shock Accelerometer. AB - On the basis of analyzing the disadvantage of other structural accelerometer, three-axis high g MEMS piezoresistive accelerometer was put forward in order to apply to the high-shock test field. The accelerometer's structure and working principle were discussed in details. The simulation results show that three-axis high shock MEMS accelerometer can bear high shock. After bearing high shock impact in high-shock shooting test, three-axis high shock MEMS accelerometer can obtain the intact metrical information of the penetration process and still guarantee the accurate precision of measurement in high shock load range, so we can not only analyze the law of stress wave spreading and the penetration rule of the penetration process of the body of the missile, but also furnish the testing technology of the burst point controlling. The accelerometer has far-ranging application in recording the typical data that projectile penetrating hard target and furnish both technology guarantees for penetration rule and defend engineering. PMID- 26353520 TI - Molecular Dynamics Simulation of Proton Transport in Polymer Electrolyte Membrane. AB - We have performed a detailed analysis of proton solvation and transport properties in hydrated Nafion using molecular dynamics simulation. The revised empirical valence bond (EVB) method was developed in order to treat the excess proton transport through the Grotthuss mechanism. The new EVB model predicts a significantly enhanced transport in comparison with previous hopping models as well as the classical hydronium diffusion, which largely improves the agreement with the available experimental data. Our results suggest that a proton hopping mechanism has a small effect on the proton dissociation from the first solvation shell of sulfonate groups, namely that protons are not enhanced to separate from the sulfonate groups by the hopping mechanisms. From diffusion comparison between the Grotthuss and vehicular mechanism, the Grotthuss mechanism dominates the proton diffusion at the studied hydration levels including a hydration level of 3. It was also found that the vehicular mechanism dominates the electroosmotic transport of water molecules at the studied hydration levels. PMID- 26353521 TI - Experimental and Numerical Study on the Droplet Formation in a Cross-Flow Microchannel. AB - It has been well established that droplets could be produced by various microchannels in many research and application areas. In this paper, we experimentally study the formation of droplets by flow focusing of two immiscible liquids in cross-flow microchannels. The used microchannels are featured by width of 100 um and depth of 60 um, which are fabricated with poly-dimethylsiloxane. The process of droplet formation is described in detail by changing the parameters which control the droplet size and generation rate. Different characteristic regimes are achieved over a large range of flow rates. We also numerically simulate the behaviors of droplets in the tested microfluidic device. The variation tendency of droplet formation frequency with different flow rates and transport properties of the continuous and dispersed phases are illustrated. The important parameters resulted from different flow conditions and configurations at the junctions and flow focusing section are also presented. PMID- 26353522 TI - Relaxation Properties of Single Layer Graphene on SiO2 Substrate. AB - The relaxation properties of single layer graphene sheet on the SiO2 substrate are investigated through molecular dynamics simulation technique in this article. The graphene sheet models with different aspect ratios on SiO2 substrate are established and sufficiently relaxed at different thermodynamic temperatures. Subsequently, the morphology, equilibrium position and undulation of graphene on SiO2 substrate are discussed. It is observed that after sufficient relaxation processes, all the graphene sheets are adsorbed on SiO2 substrates and have some certain degree of undulations both on the edge and in the inner surface rather than perfect planar structures. Further observation from the simulation results shows that with different initial distances between the graphene sheet and SiO2 substrate, the graphene sheet would eventually stabilize to an identical equilibrium level at the same temperature. In addition, the final average distance between the graphene sheet and the substrate is a constant of 3.44 A at 0.01 K, in close proximity to the value of parameter r in Lennard-Jones potential function, and the higher the temperature is, the larger the final distance becomes. The results also indicate that for the same size of the graphene sheet, the increasing of temperature significantly aggravates the undulation of graphene sheet. With the increase of aspect ratios, the undulation of the graphene sheet is also aggravated, even the graphene sheet would crimp to a certain extent. PMID- 26353523 TI - Effect of Running Parameters on Flow Boiling Instabilities in Microchannels. AB - Flow boiling instability (FBI) in microchannels is undesirable because they can induce the mechanical vibrations and disturb the heat transfer characteristics. In this study, the synchronous optical visualization experimental system was set up. The pure acetone liquid was used as the working fluid, and the parallel triangle silicon microchannel heat sink was designed as the experimental section. With the heat flux ranging from 0-450 kW/m2 the microchannel demand average pressure drop-heater length (Deltap(ave)L) curve for constant low mass flux, and the demand pressure drop-mass flux (Deltap(ave)G) curve for constant length on main heater surface were obtained and studied. The effect of heat flux (q = 188.28, 256.00, and 299.87 kW/m2), length of main heater surface (L = 4.5, 6.25, and 8.00 mm), and mass flux (G = 188.97, 283.45, and 377.94 kg/m2s) on pressure drops (Ap) and temperatures at the central point of the main heater surface (Twc) were experimentally studied. The results showed that, heat flux, length of the main heater surface, and mass flux were identified as the important parameters to the boiling instability process. The boiling incipience (TBI) and critical heat flux (CHF) were early induced for the lower mass flux or the main heater surface with longer length. With heat flux increasing, the pressure drops were linearly and slightly decreased in the single liquid region but increased sharply in the two phase flow region, in which the flow boiling instabilities with apparent amplitude and long period were more easily triggered at high heat flux. Moreover, the system pressure was increased with the increase of the heat flux. PMID- 26353524 TI - Investigation of Rotational Diffusion of a Carbon Nanotube by Molecular Dynamics. AB - The rotational diffusion coefficient of a single carbon nanotube in fluid is calculated by equilibrium and nonequilibrium molecular dynamics (MD). The validity and accuracy of the MD simulations are checked on plenty of data points by varying the length and diameter of the nanotube. The three-dimensional (3D) coefficients are larger than the two-dimensional (2D) ones, both having non- negligible deviations from the theoretical predictions [J. Chem. Phys. 1984, 81, 2047-2052]. By changing the parameter epsilonC-Ar of Lennard-Jones potential, the interaction strength between carbon and argon atoms is also taken into account. A monotonic decrease of the coefficients for both 2D and 3D cases with the increase of epsilonC-Ar can be observed. Our present work suggests that we must be cautious when using the literature theory in practical situations. PMID- 26353525 TI - Molecular Dynamics Studies on Thermal Transport Through Multiwalled Carbon Nanotubes. AB - The influence of the temperature and strength of the inter-wall interaction on the thermal conductivities of the (5,5) and (10, 10) double-walled carbon nanotubes (DWNTs) is studied by using molecular dynamics (MD) simulations with two different temperature control methods. One method is imposing heat baths (HBs) only on the outer wall, while the other is imposing HBs on both the two walls. The results show that the thermal conductivities of the DWNTs with the first method are about two-third of those with the second method. The relationship is the same even if the temperature and strength of the inter-wall interaction vary. Besides, the thermal conductivities of the DWNTs with the two different temperature control methods both slightly increase with the increasing energy parameters of Lennard-Jones (LJ) potential describing the inter-wall interaction and decrease with increasing temperature. Based on the analyses of the temperature profiles and phonon density of states (PDOS) spectra of the DWNTs with the two different temperature control methods, the results are well explained and the thermal transport mechanisms of multiwalled carbon nanotubes (MWNTs) under different conditions are explored. PMID- 26353526 TI - Mossbauer and XRD Studies of N0.6Cu0.2Zn0.2Ce(x)Fe2-xO4 Ferrites by Sol-Gel Auto Combustion. AB - In this work, stoichiometric Ni0.6Cu0.2Zn0.2Ce(x)Fe2-xO4 ferrites with 0 <= x <= 0.85 have been prepared by Sol-Gel auto-combustion method and we have investigated the effect of impurity CeO2 phase to the microstructure and hyperfine magnetic field in spinel ferrite. The results of XRD patterns confirm that the average crystallite size of samples decreases with Ce3+ substitution increasing and the lattice parameters vary as a function of x content. 57Fe Mossbuaer spectra at room temperature for all samples confirm the [Fe(3+)-O2 Fe3+] super exchange interaction decrease due to cerium substitution. For low temperature auto-combustion samples it reveals one normal sextet line and one doublet line x <= 0.25, which show well-resolved ferromagnetic order. Lattice defects are determined and Mossbuaer spectrums vary from magnetic sextet to relaxation doublet at x > 0.45 due to a mass of CeO2 phase. In contrast, the Mossbuaer spectra for the samples sintered at 800 degrees C/3 h detect the secondary phase-Fe2O3 where the cation distribution occurs and it collapses to paramagnetic doublet (x >= 0.85). So Ce3+ substitution has its maximum limit values of super exchange interaction and high sintering temperature will affect this interaction. SEM shows the crystallite of the un-doped specimen sintered at 800 degrees C/3 h form well. PMID- 26353527 TI - Raman-Based Steady-State Thermal Characterization of Multiwall Carbon Nanotube Bundle and Buckypaper. AB - Electrical methods for thermal characterization, like 3omega method, micro-bridge method and TET method have been widely used in the thermal property measurement, while always been limited by the electrical conductance of samples or other temperature dependent thermal resistors. As an optical method, Raman thermometry has been developed and broadly applied in thermal characterization in recent years. In this work, we present a steady-state method based on Raman spectroscopy for the localized thermal characterization of micro/nanowires and thin film materials, respectively. The physical models are developed and two kinds of materials: a MWCNT bundle and a piece of buckypaper are measured to validate this method. The thermal conductivities are measured as 4.92 W/m K and 0.83 W/m K for CNT bundle and buckypaper respectively. Compared with other optical methods, this steady-state Raman method features easy and fast way for thermal characterization, being capable of measuring samples from millimeters down to nanometers. PMID- 26353528 TI - Evaporation of Liquid Droplet in Nano and Micro Scales from Statistical Rate Theory. AB - The statistical rate theory (SRT) is applied to predict the average evaporation flux of liquid droplet after the approach is validated in the sessile droplet experiments of the water and heavy water. The steady-state experiments show a temperature discontinuity at the evaporating interface. The average evaporation flux is evaluated by individually changing the measurement at a liquid-vapor interface, including the interfacial liquid temperature, the interfacial vapor temperature, the vapor-phase pressure, and the droplet size. The parameter study shows that a higher temperature jump would reduce the average evaporation flux. The average evaporation flux can significantly be influenced by the interfacial liquid temperature and the vapor-phase pressure. The variation can switch the evaporation into condensation. The evaporation flux is found to remain relative constant if the droplet is larger than a micro scale, while the smaller diameters in nano scale can produce a much higher evaporation flux. In addition, a smaller diameter of droplets with the same liquid volume has a larger surface area. It is suggested that the evaporation rate increases dramatically as the droplet shrinks into nano size. PMID- 26353529 TI - Near-Field Radiative Heat Transfer Between Two SiC Plates With/Without Coated Metal Films. AB - Near-field radiation is important in many nanotechnological applications, such as thermophotovoltaic system. In this paper, we employ the Rytov theory to calculate the near-field heat transfer between two silicon carbide (SiC) plates at finite vacuum gaps. The result shows that the total energy transfer rate increases with decreasing distance, and a maximum energy transfer rate can be found with respect to frequency. We then analyze the near-field thermal radiation of an aluminum coated SiC plane in vacuum. The relation among film thickness, gap distance and energy density is given. It shows that the contribution of transverse electric (TE) mode to the energy density vanishes when the film thickness is nearly zero; and the contribution of transverse magnetic (TM) mode increases, but remains finite that can be illustrated by simple Drude model. The spectral density of p state of the thermally stimulated field in the vacuum-Al-SiC structure with fixed film thickness would have more resonance and large value can be obtained when increasing the distance; while the spectral density of p state in the thermally stimulated field in the structure with fixed distance has no apparent difference when varying the film thicknesses. This investigation can be extended for many other basic researches in near-field radiation. PMID- 26353530 TI - First-Principles Study of the Transport Properties of Graphene-Hexagonal Boron Nitride Superlattice. AB - Hexagonal boron nitride (hBN) is a promising material to be integrated with graphene for high-performance graphene based electronics. We investigate the electronic, thermal, and thermoelectric transport properties of graphene hexagonal boron nitride (G-hBN) superlattice by using the first-principles density functional calculations combined with the non-equilibrium Green's function formalism. The results show that a gap of 0.2 eV is opened in the band structure of the G-hBN superlattice due to the sublattice symmetry broken, the conductance and corresponding electron thermal conductance are both reduced. The phonon thermal conductance is also reduced due to the interlayer interactions, which linearize the flexural phonon modes and reduce the corresponding phonon density of states. Compared with those of graphene, though the electronic and phonon transport are both reduced, while the Seebeck coefficient is greatly enhanced. Finally, the thermoelectric figure of merit ZT of the G-hBN superlattice is enhanced 44% that of graphene. Our findings provide instructional information for future applications of graphene in electronics design. PMID- 26353531 TI - Synthesis and Electrochromic Properties of Star-Shaped Oligothiophene Derivatives with Triphenylamine as Core. AB - Two star-shaped oligothiophene derivatives with triphenylamine as core, Tris[4-(2 thienyl)- phenyl]amine (3TPA) and Tris[4-(5-cyano-2-thienyl)-phenyl]amine (3TPA 3CN) were synthesized and characterized for photophysical, electrochemical and electrochromic properties. The results show that introduction of cyano group to the alpha-position of thiophene unit of 3TPA-3CN makes the maximum absorption red shifted in comparison with those of 3TPA, but leads the oxidation potentials shift to positive value. Two electrochromic devices were fabricated using 3TPA and 3TPA-3CN as electroactive layer, and the electrochromic properties of both compounds were studied. 3TPA-3CN exhibits reversible, clear color change from yellow to orange on electrochemical doping and dedoping. 3TPA is electropolymerized firstly, and then switches the colors when the applied potential changes. PMID- 26353532 TI - Poiseuille Rayleigh-Benard Convective Flow and Compressible Boundary Effects of Near-Critical Fluid in Microchannels. AB - Near-critical/supercritical fluids have been widely proposed in material process, energy conversion and chemical engineering, etc. The present study is focused on the near-critical CO2 Poiseuille Rayleigh-Benard convective flow in microchannels. Careful numerical procedures are carried out by compressible Navier-Stokes equations, coupled energy and near-critical CO2 fluid state equations. In the physical model, sudden application of boundary heat fluxes in the boundaries is assumed. The flow and heat transfer characteristics of such Poiseuille Rayleigh-Benard configuration in microscales are systematically explored. For the convection onset, strong near-critical vortex flows are found for a relative wide range of initial and input conditions in microchannels. It is found that typical near-critical thin, hot boundary layer (HBL) plays critical role in the basic stability evolution process. The hot boundary layer formation process and the characteristics of the transition phenomena, convection structure, heat transfer behaviors as well as future development are also presented in this paper. It is hoped that this study can contribute to near critical hydrodynamics in microscales. PMID- 26353533 TI - Near-Wall Velocity and Temperature Measurements in the Meniscus Region for Staggered Glass Beads. AB - Velocity and temperature fields in the meniscus are crucial for the heat transfer mechanism in porous medium. The meniscus zone, however, is narrow so that it is difficult for observation. The velocimetry and thermometry in the near-wall region of the surface provide possible measurement methods with the development of micro/nanotechnology. Being exponentially decay in the intensity, the evanescent-wave illumination has the advantage of high spatial resolution and non intrusion for these measurement methods. The multilayer nano-particle image velocimetry (MnPIV) uses the evanescent-wave illumination, decayed exponentially with the wall-normal distance, to obtain near-wall velocity data at different distances from the wall. The thermometry in the meniscus region could also use the evanescent-wave to illuminate the fluorescence dye, the emitted intensity of which changes with temperature. In this paper, these techniques are employed to measure the near-wall velocity and temperature between the porous media and the ITO heater, in order to explore the role of meniscus during convection of water. Near-wall velocity and temperature of the deionized water, seeded with 100 nm fluorescent colloidal tracers and flow in the staggered glass beads with diameters ranging from 2 mm to 6 mm, are obtained and discussed. PMID- 26353534 TI - Influence of Environmental Factors on the Adsorption Capacity and Thermal Conductivity of Silica Nano-Porous Materials. AB - In this work, the influence of temperature and humidity environment on the water vapor adsorption capacity and effective thermal conductivity of silica nano porous material is conducted within a relative humidity range from 15% to 90% at 25 degrees C, 40 degrees C and 55 degrees C, respectively. The experiment results show that both the temperature and relative humidity have significant influence on the adsorption capacity and effective thermal conductivity of silica nano-porous materials. The adsorption capacity and effective thermal conductivity increase with humidity because of the increases of water vapor concentration. The effective thermal conductivity increases linearly with adsorption saturation capacity at constant temperature. Because adsorption process is exothermic reaction, the increasing temperature is not conducive to the adsorption. But the effective thermal conductivity increases with the increment of temperature at the same water uptake because of the increment of water thermal conductivity with temperature Geometric models and unit cell structure are adopted to predict the effective thermal conductivity and comparisons with the experimental result are made, and for the case of moist silica nano-porous materials with high porosity no quantitative agreement is found. It is believed that the adsorbed water will fill in the nano-pores and gap and form lots of short cuts, leading to a significant reduction of the thermal resistance. PMID- 26353535 TI - Dependence of Photothermal Conversion Characteristics on Different Nanoparticle Dispersions. AB - The efficiency of nanoparticle-based direct absorption solar collector (DASC) is strongly dependent on the materials, where a systematic study is still lacking. This work conducts an experimental study of the photothermal conversion characteristics of a number of nanoparticle dispersions including Au, Si, Fe3O4, Al2O3 and diamond under the same experimental setup. The results show that comparing with the base fluid, the introduction of nanoparticles can increase the photothermal conversion efficiency significantly, and the efficiency increases in the order of Al2O3, diamond, (Fe3O4 and Si) and Au. For a given total mass concentration, the Fe3O4-Au hybrid nanofluid is found to possess a higher efficiency than that of pure Au alone. Three possible mechanisms are proposed for the influence of nanoparticle materials, which can qualitatively explain the experimental results. PMID- 26353536 TI - Flow and Thermal Performance of a Water-Cooled Periodic Transversal Elliptical Microchannel Heat Sink for Chip Cooling. AB - Flow and thermal performance of transversal elliptical microchannels were investigated as a passive scheme to enhance the heat transfer performance of laminar fluid flow. The periodic transversal elliptical micro-channel is designed and its pressure drop and heat transfer characteristics in laminar flow are numerically investigated. Based on the comparison with a conventional straight micro- channel having rectangular cross section, it is found that periodic transversal elliptical microchannel not only has great potential to reduce pressure drop but also dramatically enhances heat transfer performance. In addition, when the Reynolds number equals to 192, the pressure drop of the transversal elliptical channel is 36.5% lower than that of the straight channel, while the average Nusselt number is 72.8% higher; this indicates that the overall thermal performance of the periodic transversal elliptical microchannel is superior to the conventional straight microchannel. It is suggested that such transversal elliptical microchannel are attractive candidates for cooling future electronic chips effectively with much lower pressure drop. PMID- 26353537 TI - Enhanced Rate Capability of Polymer-Derived SiCN Anode Material for Electrochemical Storage of Lithium with 3-D Carbon Nanotube Network Dispersed in Nanoscale. AB - Electrochemical performances of multi-walled carbon nanotubes (CNT)-SiCN composite have been investigated. The sample was synthesized by a simple ultrasonication assisted method combined with high-temperature pyrolysis and characterized by Fourier transform infrared spectra, Raman spectra, X-ray diffraction, field emission scanning electron microscopy and transmission electronic microscopy. In this composite, CNT were uniformly distributed in the SiCN ceramic matrix, it retained the structural integrity during the polymer ceramic conversion and had a relatively strong bonding with the SiCN ceramic matrix. When tested as anode in the half cell, the obtained composite exhibited enhanced rate capability and cyclic capacity than that of pristine SiCN powder, CNT and graphite, it could supply a capacity of 222.7 mA h/g when charged at 2000 mA/g, while the SiCN anode showed nearly no capacity even at the low current density of 200 mA/g. It is expected that the CNT-SiCN composite, perhaps the series of CNT-PDC composites, may be prospective candidate for high power applications. PMID- 26353538 TI - Effects of WO3 Micro/Nano-Inclusions on the Thermoelectric Properties of Co4Sb11.7Te0.3 Skutterudite. AB - In this study, nano-sized WO3 powder was dispersed into Co4Sb1.7Te0.3 thermoelectric matrix by ball milling and hot-press sintering technology. The results of scanning electron microscopy (SEM) showed that the WO3 phase distributed uniformly in the form of inclusions on the matrix. High-resolution transmission electron microscopy (HRTEM) presented that the average size of embedded nano-WO3 was about 50 nm. With the content of WO3 increasing, the electrical conductivity (sigma) of Co4Sb11.7Te0.3 decreased and the absolute value of Seebeck coefficient (a) increased. The absolute value of a for 1.5% WO3/Co4Sb11.7Te0.3 composite was 258 uV/K at 650 K. The minimal lattice thermal conductivity (K(L)) of WO3/Co4Sb11.7Te0.3 achieved in the present work was 1.52 W/m K at 650 K. The total thermal conductivity (K) of WO3/Co4Sb11.7Te0.3 composites decreased obviously, which resulted from the phonon scattering by the WO3 inclusions locating on the grain boundaries of Co4Sb11.7Te0.3 matrix. The highest ZTof 0.71 was achieved at 750 K for 1.5%WO3/Co4Sb11.7Te0.3 composite. PMID- 26353539 TI - Three-Dimensional Numerical Simulation of Vesicle Dynamics in Microscale Shear Flows. AB - Flow behaviors of blood strongly depend on dynamics of red blood cells (RBCs) under flow. Due to the simplicity, vesicles have been extensively used as a model system to investigate RBC dynamics. Despite its significance in microfluidics, the effect of confinement (i.e., ratio of vesicle size to microchannel size) on vesicle dynamics has not been reported in three-dimensional (3D) modeling. In this study, we developed a 3D mathematical model and investigated the effect of confinement on the dynamics of oblate-shaped vesicles in microscale shear flows. Our results indicated that confinement has significant effect on the dynamics of vesicles, including tank-treading, swinging and tumbling. An increase of confinement can induce the transition of vesicle dynamics from tumbling to swinging. This study could be helpful to future studies on the flow of vesicle suspensions at microscale, e.g., in vivo capillaries and in vitro microfluidics. PMID- 26353540 TI - Experimental and Numerical Study on Thermal Conductivity of Proton Exchange Membrane. AB - In this paper, the thermal conductivity of dry Nafion 117 is measured by Hot Disk TPS2500 and a molecular dynamics calculation model for the proton exchange membrane is constructed by Materials Studio (MS) software platform to study its thermal conductivity. Cell structures of different water content of Nafion membrane at 300 K and 330 K are obtained, respectively. It is found that at the same temperature the predicted thermal conductivity of PEM increases with the water content, and at the same water content the predicted thermal conductivity decreases with the temperature. So both the water content and temperature are important factors affecting thermal conductivities of PEM. PMID- 26353541 TI - Chirality and Diameter Influence on Thermal Conductivity of Single-Walled Carbon Nanotubes. AB - Influence of chirality and diameter on thermal conductivity of Single-Walled Carbon Nanotube (SWNT) with different tube lengths have been investigated using non-equilibrium molecular dynamics (NEMD) method. The tube lengths of the SWNTs studied here are 20, 50 and 100 nm, respectively, and at each length the relationship between chiral angle and thermal conductivity of SWNT has been revealed; the dependence of thermal conductivity on diameter has also been studied. We find that chirality impact on thermal conductivity of SWNT is more obvious when tube length is relatively shorter, while diameter effect is more noticeable when tube gets longer. With larger chiral angle, thermal conductivity of chiral SWNTs is greater than that with smaller chiral angle and thermal conductivity increases with diameter. PMID- 26353542 TI - Phase Transition Experimental and Theoretical Study of Micro Power Generator Supplying Source for CMOS Chip Based on Ferroelectric Ceramic Nano-Porous Material. AB - We demonstrated both experimentally and in theory analysis and calculation that the tin-modified lead zirconate titanate nanoporous ferroelectric generator system can perform as a micro-power supplying source for CMOS chip. The ferroelectric ceramic phase transition under transverse shock wave compression can charge external storage capacitor. The nanoporous microstructure ferro electric ceramic micro-pulsed-power system is capable of generating low output voltage pulses and supplying CMOS chip with micro power sources. We developed the methodology for theory analysis and experimental operation of the ferroelectric generator. Analysis of the porous ferroelectric ceramic material was carried out by X-ray diffractometry and X-ray photoelectron spectroscopy. Microstructures and surface morphology of porous ferroelectric ceramics samples were examined by using scanning electron microscopy. The planar shock wave experiments were conducted on a compressed-gas gun. The experimental results were in good agreement with the theory analysis. Keywords: PSZT Ferroelectric Ceramic, Shock Wave, Phase Transition, Depolarization, Micro-Power-Generator. PMID- 26353543 TI - Ultra-Thin Monocrystalline Silicon Solar Cell with 12.2% Efficiency Using Silicon On-Insulator Substrate. AB - Single side heterojunction silicon solar cells were designed and fabricated using Silicon-On-Insulator (SOI) substrate. The TCAD software was used to simulate the effect of silicon layer thickness, doping concentration and the series resistance. A 10.5 um thick monocrystalline silicon layer was epitaxially grown on the SOI with boron doping concentration of 2 x 10(16) cm(-3) by thermal CVD. Very high Voc of 678 mV was achieved by applying amorphous silicon heterojunction emitter on the front surface. The single cell efficiency of 12.2% was achieved without any light trapping structures. The rear surface recombination and the series resistance are the main limiting factors for the cell efficiency in addition to the c-Si thickness. By integrating an efficient light trapping scheme and further optimizing fabrication process, higher efficiency of 14.0% is expected for this type of cells. It can be applied to integrated circuits on a monolithic chip to meet the requirements of energy autonomous systems. PMID- 26353544 TI - Structured Single-Walled Carbon Nanotubes and Graphene for Solar Cells. AB - We propose the concept of structured single-walled carbon nanotubes (SWNTs) for the applications of heterojunction solar cells and dye-sensitized solar cells (DSSCs). The structure of SWNTs was controlled and modified by a simple water vapor treatment, which was originally developed by our group. Compared with the graphene-Si solar cell and the SWNT-Si solar cell using the random-oriented SWNT film, the pristine micro-honeycomb structured SWNT-Si solar cell shows a significant improvement in terms of fill factor and the greater potential to obtain high power conversion efficiency (PCE). Moreover, the performance of the pristine micro-honeycomb structured SWNT-Si solar cells is stable in ambient condition. In addition, the PCE and fill factor of the DSSC with the micro honeycomb structured SWNT counter electrode are 3.90% and 0.61, respectively, which are comparable to those of the DSSC with Pt as the counter electrode. This result shows that the micro-honeycomb networked SWNTs provide a low-cost alternative to replace Pt in DSSCs. PMID- 26353545 TI - Sulfur-Doping Templated Synthesis of Nanoporous Graphitic Nanocages and Its Supported Catalysts for Efficient Methanol Oxidation. AB - We demonstrate a new sulfur (S)-doping templated approach to fabricate highly nanoporous graphitic nanocages (GNCs) by air-oxidizing the templates in the graphitic shells to create nanopores. Sulfur can be introduced, when Fe@C core shell nanoparticles are prepared and then S-doped GNCs can be obtained by removing their ferrous cores. Due to removing S-template, both the specific surface area (from 540 to 850 m2 g(-1)) and the mesopore volume (from 0.44 to 0.9 cm3 g(-1)) of the graphitic nanocages have sharply risen. Its high specific surface area improves catalyst loading to provide more reaction electro-active sites while its high mesopore volume pro- motes molecule diffusion across the nanocages, making it an excellent material to support Pt/Ru catalysts for direct methanol fuel cells. PMID- 26353546 TI - Extraction of the Density Fluctuations in Diatomic Fluids Around the Critical Points Using Molecular Dynamics Simulation. AB - The objective in this study is the investigation of the principle of corresponding state for the density fluctuation around the critical points of non polar diatomic fluids. In this paper, we conducted Molecular Dynamics (MD) simulation for the extraction of the fluctuation structure around the critical points of 2-Center-Lennard-Jones (2CLJ) fluids, which have anisotropy depending on the molecular elongation. As a result, in the 2CLJ fluids which have comparatively shorter molecular elongations, the principle of corresponding state can be satisfied because almost all density fluctuations in each elongation showed the similar values. On the other hand, some of the results suggested that the 2CLJ fluids which have the longer elongation decrease the density fluctuation although the further detailed investigation is necessary. PMID- 26353547 TI - Thermal Properties of Polymethyl Methacrylate Composite Containing Copper Nanoparticles. AB - Thermal functional Materials have wide applications in thermal management fields, and inserting highly thermal conductive materials is effective in enhancing thermal conductivity of matrix. In this paper, copper nanoparticles were selected as the additive to prepare polymethyl methacrylate (PMMA) based nanocomposite with enhanced thermal properties. Uniform copper nanoparticles with pure face centered lattice were prepared by liquid phase reduction method. Then, they were added into PMMA/N, N-Dimethylmethanamide (DMF) solution according to the different mass fraction for uniform dispersion. After DMF was evaporated, Cu-PMMA nanocomposites were gained. The thermal analysis measurement results showed that the decomposition temperature of nanocomposites decreased gradually with the increasing particle loadings. The thermal conductivity of the Cu-PMMA nanocomposites rose with the increasing contents of copper nanoparticles. With a 20 vol.% addition, the thermal conductivity was up to 1.2 W/m . K, a 380.5% increase compared to the pure PMMA. The results demonstrate that copper nanoparticles have great potential in enhancing thermal transport properties of polymer. PMID- 26353548 TI - Development of a Biomedical Micro/Nano Robot for Drug Delivery. AB - Flagellated bacteria have been utilized as potential swimming micro-robotic bodies for propulsion of spherical liposome by attaching several bacteria on their surface. Liposome as a drug delivery vehicle can contain biologically active compounds. In this work, the antibody binding technique is developed to attach bacteria to liposome's surface. Consequently, the stochastic effect of bacterial propulsion of liposome is investigated analytically and experimentally. It is shown that the mobility of liposome with bacteria was higher than that of liposome without bacteria. Experimental data matches well with statistical calculation. PMID- 26353549 TI - Electrochromic Properties of Acid Dye Doped Poly(3,4-ethylenedioxythiophene) by Electropolymerization. AB - The electrochromic properties of an electrochemical polymerized composite consisted of poly(3,4-ethylenedioxythiophene) doped with acid red G (PEDOT-ARG) are reported. The structures of PEDOT-ARG were characterized via cycle voltammograms, spectroelectrochemistry and colorimetric analysis. Film of the PEDOT-ARG composites switches from aubergine in the reduction state to light blue in the oxidized state, which is different from the pure PEDOT of dark blue (-0.8 V) and light blue (1.0 V). Because of the big molecule of acid red G as the dopant, the response time reaching 90% of the full optical contrast of PEDOT-ARG was 5.7 s for the oxidation process and 5.4 s for the reverse reduction process, which is a little slower than the pure PEDOT. Additionally, the colorimetric analysis results show that components of red in PEDOT-ARG films become stronger than the pure PEDOT films at the whole electrochromic process. It is shown that acid dye doping is an effective method to broaden the color change range of the electrochromic materials. PMID- 26353550 TI - Thermal Conductivity of Eutectic Nitrates and Nitrates/Expanded Graphite Composite as Phase Change Materials. AB - Nitrates and eutectic nitrate mixtures are considered as potential phase change materials (PCMs) for the middle-temperature-range solar energy storage applications. But the extensive utilization is restricted by the poor thermal conductivity and thermal stability. In the present study, sodium nitrate potassium nitrate eutectic mixture was used as the base PCM, and expanded graphite (EG) was added to the mixture so as to improve the thermal conductivities. The elaboration method consists of a physically mixing of salt powders with or without EG, and the composite PCMs were cold-compressed to form shape-stabilized PCMs at room temperature. The thermal conductivities of the composite PCMs fabricated by cold-compression were investigated at different temperatures by the steady state method. The results showed that the addition of EG significantly enhanced the thermal conductivities. The thermal conductivities of pure nitrates and nitrates/EG composite PCMs in solid state showed the behavior of temperature dependant, and they slightly decreased with the increase of the temperature. PMID- 26353551 TI - A Molecular Dynamics Study on Wetting Phenomena at a Solid Surface with a Nanometer-Scale Slit Pore. AB - Non-equilibrium molecular dynamics simulations are conducted for the liquid wetting phenomena on a solid surface with a nanometer-scale slit pore. All interactions between molecules or atoms are assumed to be 12-6 Lennard-Jones (LJ) potential in order to examine the fundamental mechanisms of the wetting phenomena qualitatively. The Lorentz-Berthelot combining rule is applied to obtain the standard parameters between fluid molecules and solid atoms, which are controlled by using relative parameters to change the interaction intensity. The energy of fluid molecules in the vicinity of the entrance of the slit pore is investigated in detail so as to elucidate the mechanism of the liquid wetting phenomena from a molecular energy point of view. The results show that the total energy per unit volume of fluid molecules in the vicinity of the solid surface inside the slit pore becomes lower than that of the bulk part of the liquid membrane which exists outside the slit pore when the wetting phenomena occur. PMID- 26353552 TI - Preparation and Thermoelectric Properties of Co-Doped ZnO Synthesized by Sol-Gel. AB - Zinc oxide (ZnO) has attracted increasing attention as one of the most promising n-type thermo-electric materials, but its practice use was limited by high thermal conductivity and low electrical conductivity. Therefore, we herein prepared Co-doped ZnO nanoparticles by sol-gel method and then compressed nanoparticles into bulk materials through spark plasma sintering. The thermo electric properties, including electrical conductivity, Seebeck coefficient, thermal conductivity, and ZT value, have been investigated. We found that the substitution of Co2+ causes the decrease of bandgap and the increase of carrier concentration, thus the improvement of electrical conductivity. At the same time, the Co-induced lattice distortion and nanoparticles reduce the thermal conductivity by shortening the mean free path (MFP) of the phonons. The resultant ZT is 0.037 for Zn0.9Co0.1O, which is more than 23-fold higher than that of the pure ZnO samples. PMID- 26353553 TI - Fabrication and Application of a New-Type Photothermal Conversion Nano Composite Coating. AB - Photothermal conversion nanomaterials attract much attention for their high light/heat transform efficiency and controllable light absorption. In this work, the CuS semiconductor nanomaterials were prepared through the deposition method in the presence of citrate sodium and were characterized by TEM, XRD and UV-vis spectra. A new type of nano composite coating was obtained from acrylic resin by adding the CuS nanoparticles and other nanomaterials which could absorb the light of various infrared bands. The test showed that when exposed to infrared light, the plastic greenhouse model equipped with photothermal conversion coating gave out a more significant temperature rising than that of the common plastic greenhouse. The properties of photothermal conversion and heat insulation of photothermal conversion coating reach the best when the addition quantities of CuS and ZrC nanoparticles are 2%. PMID- 26353554 TI - Preparation and Properties of Fibrous Fe3O4/Polyaniline Nanocomposites. AB - By using inorganic Fe3O4 nanoparticles as nucleation sites, Fe3O4/polyaniline magnetic nanocomposites are successfully synthesized by chemical oxidative polymerization method. The morphology and properties of Fe3O4/polyaniline nanocomposites are characterized by XRD, FTIR, TEM, DSC, TG and VSM. XRD, FTIR and DSC jointly indicate that the composites comprise Fe3O4 and polyaniline. TEM micrographs indicate that the Fe3O4 magnetic nanoparticles have an average diameter less than 20 nm and achieve better property of dispersion after composited with polyaniline. With the content of polyaniline increasing, Fe3O4/polyaniline composites change from aggregated particles to fibers. Fibrous composites achieve excellent thermal stability and attractive polyaniline content dependence of magnetism. TG analyses reveal that apparent weight loss of the fibrous composite appears at higher temperature than the granular Fe3O4/polyaniline composite does. With the increasing of the content of polyaniline, the magnetism of Fe3O4/polyaniline composite change from ferromagnetism to paramagnetism, while the magnetization decreases firstly and then increases. The formation of fibrous Fe3O4/polyaniline composite is favorable for the magnetization. PMID- 26353555 TI - The Numerical Simulation of Liquid-Vapor Stratified Flow in Horizontal Metal-Foam Tubes. AB - In this paper, a boiling stratified flow model in a metal-foam tube is proposed. First, based on Branuer non-equilibrium gas-liquid interface model, a force balance on the gas-liquid interface in metal-foam is calculated. The shape of the interface of upper gas phase and lower liquid phase in metal foam tube is obtained. As for the lower liquid phase, the energy conservation equations of liquid and metal foam are formulated, which account for porosity and fiber diameter of foam on the basis of non-local thermal equilibrium model (NTEM), respectively. Therefore, a profile of temperature difference between liquid and metal foam can be obtained. For the upper gas phase, an empirical correlation developed by other researchers is utilized to obtain temperature difference between gas phase and solid wall. In addition, the variation of the Reynolds number with increasing mass quality along the flow direction is acquired. Ultimately, an average circumference heat transfer coefficient is calculated. The results of circumference heat transfer coefficient agree well with available experimental data, showing the prediction of the proposed stratified flow model is feasible. The reason resulting in discrepancies between the prediction and experiment data is also illustrated. PMID- 26353556 TI - The Effect of Nanometer Oxide Additive on the Heat-Conducting Property of Barium Hydroxide Octahydrate. AB - Nanometer silicon dioxide additive can improve the thermal performance of barium hydroxide octahydrate as the phase change thermal energy storage material. Through measuring the changes of phase change temperature, degree of supercooling, thermal conductivity, the different effects of nanometer silicon dioxide additives of different mass fraction on barium hydroxide octahydrate thermal performance are compared. It can be seen that the precipitation of barium hydroxide octahydrate with nanometer silicon dioxide additive of 0.5% mass fraction improves greatly. The thermal conductivity of barium hydroxide octahydrate with nanometer silicon dioxide additive of 0.5% mass fraction increases to a very slight degree. PMID- 26353557 TI - Raman Enhancement Caused by Gold Nanoparticles Clustered Between Graphene and Substrate. AB - Graphene, one of the most robust two-dimensional (2D) materials, has shown amazing electrical, optical and thermal properties. The contact of graphene to other materials leads to Raman enhancement or fluorescence variation in some cases. Here, we present one flexible substrate structure of graphene/clustered gold-nanoparticles (CGNs)/PDMS to demonstrate the Enhanced Surface Raman Spectroscopy. The fluorescence quenching on graphene is explained as ground-state charge transfer. In addition, graphene is found to possess the ability of fluorescence quenching or Raman enhancement when there are CGNs underneath. Moreover, graphene can be used as a passivation layer, protecting the CGNs underneath from chemical bonding with other materials. The experimental results also confirm that the total extra Raman enhancement is attributed to the extra electron shift to graphene and the extra ground state charge transfer introduced by the CGNs. This artificially engineered structures based on 2D materials could yield characteristics that go far beyond those conventional materials, and such materials should lead to higher sophistication of optical manipulation. PMID- 26353558 TI - Optical Absorption and Photo-Thermal Conversion Properties of CuO/H2O Nanofluids. AB - Stable CuO/H2O nanofluids were synthesized in a wet chemical method. Optical absorption property of CuO/H2O nanofluids was investigated with hemispheric transmission spectrum in the wavelength range from 200 nm to 2500 nm. Photo thermal conversion property of the CuO/H2O nanofluids was studied with an evaluation system equipped with an AUT-FSL semiconductor/solid state laser. The results indicate that CuO/H2O nanofluids have strong absorption in visible light region where water has little absorption. Under the irradiation of laser beam with a wavelength of 635 nm and a power of 0.015 W, the temperature of CuO/H2O nanofluids with 1.0% mass fraction increased by 5.6 degrees C within 40 seconds. Furthermore, the temperature elevation of CuO/H2O nanofluids was proved to increase with increasing mass fractions. On the contrast, water showed little temperature elevation under the identical conditions. The present work shows that the CuO/H2O nanofluids have high potential in the application as working fluids for solar utilization purpose. PMID- 26353559 TI - Structural, Infrared and Magnetic Properties of Nanosized Ni(x)Zn1-xFe2O4 Powders Synthesized by Sol-Gel Technique. AB - Ni-Zn ferrites Ni(x)Zn1-xFe2O4 (x = 0.2, 0.4, 0.5, 0.6, 0.8) powders were synthesized by sol-gel technique. Structural, infrared and magnetic properties of samples were investigated. Spinel structural characteristics are shown by XRD spectra and the morphologies observed by atomic force microscopy demonstrate the samples are in nano-range. For all the samples, FTIR spectra exhibit obvious v1 infrared absorbing bands, in the range 500-600 cm-1, corresponding to intrinsic stretching vibrations of the metal ions at the tetrahedral site (Td), Mtetra <--> O. Furthermore, the central position of v1 band is tending to shift to larger wave numbers with the increasing Ni contents in the samples. For the samples Ni(x)Zn1-xFe2O4 (x = 0.2, 0.4), the v2 infrared absorbing bands, in the range 450 385 cm(-1), corresponding to stretching vibrations of the metal ions at the octahedral-metal stretching (Oh), Mocta <--> O, were also observed. However, for samples Ni(x)Zn1-xFe2O4 with higher Ni content (x = 0.5, 0.6, 0.8), the v2 infrared absorbing bands were obscure. The magnetic hysteretic loops at room temperature obtained from vibration samples magnetometer reveal the soft magnetism of the samples. The sample with lowest Ni content, Ni0.2Zn0.8Fe2O4, presents much higher saturation field than the other samples. The coercive field rises with increased Ni content, which is ascribed to the increased magnetocrystalline anisotropy constant with Ni content. PMID- 26353560 TI - Phonon Transmission Across the Si-Ge Interface. AB - Interfaces play an important role in nanostructured structures, which have been widely employed to improve the efficiency of thermoelectric materials. Knowledge of how each specific phonon is scattered at an interface are desired to develop novel nanostructured materials with desired thermal properties. Phonon transmission across the interface consisting of silicon (Si) and germanium (Ge) is investigated by using lattice dynamics. It is found that there exists a critical phonon frequency for the thermal transport across the Si-Ge interface. When the phonon frequency is higher than 198 cm(-1), the phonon transmission coefficient is considerably low, which mean that phonons with higher frequencies contribute little to the thermal transport across the Si-Ge interface. While the phonon frequency goes lower than 198 cm(-1), the phonon transmission coefficient becomes much higher, inferring that phonons with lower frequencies contribute dominantly to the thermal conductance at the Si-Ge interface. This is helpful for understanding the underlying mechanisms of phonon transmission across a Si-Ge interface. PMID- 26353561 TI - Photo-Thermal Conversion of Copper Sulfide Hollow Structures with Different Shape and Thickness. AB - In the current paper, we report the synthesis of spherical and cubic copper sulfide hollow structures, as well as the influence of shape and thickness on the photo-thermal conversion of the as-synthesized products. Copper sulfide hollow structures of different thickness were synthesized base on a sacrificial template strategy using spherical and cubic Cu2O precursors as templates. Optical absorption of the as-synthesized products was investigated with UV-Vis spectrometer. Photo-thermal conversion property was studied with a lab-made evaluation system equipped with an AUT-FSL semiconductor/solid state laser. The results indicate that the as-prepared products exhibited significant absorption in visible light regions. Under the irradiation of laser beam with a wavelength at 635 nm and a power of 0.015 W, the temperature elevations of the aqueous suspensions containing 0.24% mass fraction of spherical and cubic copper sulfide hollow structures were measured to be 5 degrees C and 6 degrees C within 60 seconds, respectively. On the contrast, water showed little temperature elevation under the same conditions. PMID- 26353562 TI - Effects of Ni Deposition on the Electrochemical Properties of CNT/Ni Electrode and Its Application for Glucose Sensing. AB - A low density CNT forest was fabricated by plasma enhanced chemical vapor deposition, and Ni nanoclusters were well distributed on the sidewall and on top of CNT forest by magnetron sputtering. The Ni deposition time plays an important role in electrochemical properties of the CNT/Ni electrodes, and the optimized deposition time is 150 to 240 s. Cyclic voltammetry and chronoamperometry were used to evaluate the catalytic activities of the CNT/Ni electrodes. The sensitivity of the glucose sensor based on a Ni24OS electrode is able to reach 1433 uA mM(-1) cm(-2), which is much higher than that found using a NiOS electrode. PMID- 26353563 TI - Analytical Fractal Model for Calculating Effective Thermal Conductivity of the Fibrous Porous Materials. AB - Accurately predicting the effective thermal conductivity of the fibrous materials is highly desirable but remains to be a challenging work. In this paper, the microstructure of the porous fiber materials is analyzed, approximated and modeled on basis of the statistical self-similarity of fractal theory. A fractal model is presented to accurately calculate the effective thermal conductivity of fibrous porous materials. Taking the two-phase heat transfer effect into account, the existing statistical microscopic geometrical characteristics are analyzed and the Hertzian Contact solution is introduced to calculate the thermal resistance of contact points. Using the fractal method, the impacts of various factors, including the porosity, fiber orientation, fractal diameter and dimension, rarified air pressure, bulk thermal conductivity coefficient, thickness and environment condition, on the effective thermal conductivity, are analyzed. The calculation results show that the fiber orientation angle caused the material effective thermal conductivity to be anisotropic, and normal distribution is introduced into the mathematic function. The effective thermal conductivity of fibrous material increases with the fiber fractal diameter, fractal dimension and rarefied air pressure within the materials, but decreases with the increase of vacancy porosity. PMID- 26353564 TI - Liquid Cooling of Tractive Lithium Ion Batteries Pack with Nanofluids Coolant. AB - The heat generated from tractive lithium ion batteries during discharge-charge process has great impacts on the performances of tractive lithium ion batteries pack. How to solve the thermal abuse in tractive lithium ion batteries pack becomes more and more urgent and important for future development of electrical vehicles. In this work, TiO2, ZnO and diamond nanofluids are prepared and utilized as coolants in indirect liquid cooling of tractive lithium ion batteries pack. The results show that nanofluids present superior cooling performance to that of pure fluids and the diamond nanofluid presents relatively excellent cooling abilities than that of TiO2 and ZnO nanofluids. During discharge process, the temperature distribution of batteries in batteries pack is uniform and stable, due to steady heat dissipation by indirect liquid cooling. It is expected that nanofluids could be considered as a potential alternative for indirect liquid cooling in electrical vehicles. PMID- 26353565 TI - Enhancing Thermal Conductive Performance of Vertically Aligned Carbon Nanotube Array Composite by Pre-Annealing Treatment. AB - Vertically aligned carbon nanotube (VACNT) array/polymer composite has already been recognized as a promising candidate for advanced thermal pad in thermal management of high-power electronic devices. However, the thermal conductive performance of this composite was limited by the quality of CNTs arrays. In this study, pre-annealing treatment was used to purify CNT arrays and improve thermal conductive performance of VACNT arrays/silicone composite. The thermal conductivity of the composite was enhanced by 34.52% and the thermal interface resistance was also reduced by 65.94% at a pre-annealing temperature of 490 degrees C for 5 min. The annealing process could remove some amorphous carbon and open the tips of CNTs. As a result, the interfacial compatibility in composite between carbon nanotube and polymer matrix was improved. The cyclic compression and tension performance of VACNT/S160 composite was investigated for further application. PMID- 26353566 TI - Study on Unit Cell Models and the Effective Thermal Conductivities of Silica Aerogel. AB - In this paper, two modified unit cell models, truncated octahedron and cubic array of intersecting square rods with 45-degree rotation, are developed in consideration of the tortuous path of heat conduction in solid skeleton of silica aerogel. The heat conduction is analyzed for each model and the expressions of effective thermal conductivity of the modified unit cell models are derived. Considering the random microstructure of silica aerogel, the probability model is presented. We also discuss the effect of the thermal conductivity of aerogel backbone. The effective thermal conductivities calculated by the proposed probability model are in good agreement with available experimental data when the density of the aerogel is 110 kg/m3. PMID- 26353567 TI - Molecular Dynamics Study for Channel Size Dependence of Shear Stress Between Droplet and Wall. AB - In this study, the channel size dependence of the shear stress between water droplets and solid walls in nm-order channel was analyzed. We considered a several different-sized and highly hydrophobic channel whose macroscopic contact angle was about 150 degrees. We have evaluated the shear stress and the normal pressure by molecular dynamics simulation. Analyzing shear stress and normal pressure based on the macroscopic model, we have discussed the difference between the macroscopic model based on hydrodynamics and the microscopic model. As a result, in the high hydrophobic case, it became clear that the shear stress depends on the channel size due to the large Laplace pressure. Furthermore, in the case that the channel size was less than 50 A, the normal pressure by the molecular simulation didn't agree with the expected value from the Young-Laplace equation. From this study it was clear that molecular simulation is needed when the channel size is less than 40 A. PMID- 26353568 TI - Hydrodynamic Modeling of Heat Conduction in Nanoscale Systems. AB - Heat conduction in nanoscale systems has different behavior from bulk materials, which is applied to develop high performance thermoelectric material. The non trivial behavior is caused by the ballistic-diffusive transport of heat carriers such as phonons. In this paper, we use the thermomass theory and phonon hydrodynamics model to establish a hydrodynamic model for phonon transport. In nanoscale systems, a Poiseuille flow of phonon gas is formed due to the boundary scattering. The thickness of boundary layer is proportional to the mean free paths of phonon. When the boundary layer thickness is comparable with the whole flow region, strong decrease of effective thermal conductivity happens. This method can serve as a fast evaluation method for nanoscale heat conduction. PMID- 26353569 TI - Influences of Ni Doping on the Morphology, Optical and Magnetic Properties of ZnO Nanostructures Synthesized by Solvothermal Process. AB - Pure and Ni-doped ZnO nanostructures have been synthesized by a solvothermal process. The structure, morphology and properties of as-synthesized samples have been investigated using X-ray diffraction (XRD), scanning electron microscope (SEM), transmission electron microscopy (TEM), energy dispersive spectroscopy (EDS), selected-area electron diffraction (SAED), UV-vis spectrometer as well as by vibrating sample magnetometer (VSM). XRD and EDS studies indicated that the as prepared products were well-crystallized wurtzite hexagonal structure. The SEM and TEM images show that the individual Zn0.96Ni0.04O nanostructure is composed of several nanorods with average diameter of 200 nm and lengths of 500 nm. The structure and morphology analyses show that Ni doping can influence the nanostructures morphology, but cannot change the crystal structures of ZnO samples. The UV-vis spectra showed that Ni dopant can result in an appreciable blue-shift for the absorption edge of the Ni-doped ZnO samples. The band gap energy of the Zn0.96Ni0.04O nanostructure was about 3.23 eV. By magnetic measurements, it was observed that the pure ZnO nanostructure exhibits diamagnetic property while the sample of 4% Ni shows an obvious ferromagnetic behavior at room temperature due to the formation of solid solution Zn0.96Ni0.04O, sp-d and d-d carrier exchange interactions, and the presence of abundant defects and oxygen vacancies. PMID- 26353570 TI - Facile Preparation and Self-Assembly of Monodisperse Polystyrene Nanospheres for Photonic Crystals. AB - We have developed boiling emulsifier-free emulsion polymerization recipes for the synthesis of monodisperse polystyrene (PS) nanospheres with diameters between ca. 100 and 300 nm. The morphologies of the nanospheres during growth were characterized and the results showed that the PS nanospheres with uniform structures could be synthesized rapidly by modifying the reaction conditions. These nanospheres readily self-assemble into three-dimensionally colloidal photonic crystal film and whose photonic band-stop could be tuned over the entire visible spectral region by altering the sphere diameters. PMID- 26353571 TI - Thermal Conductivity of Natural Rubber Using Molecular Dynamics Simulation. AB - Thermal conductivity of natural rubber has been studied by classic molecular dynamics simulations. These simulations are performed on natural rubber models using the adaptive intermolecular reactive empirical bond order (AIREBO) and the Green-Kubo molecular dynamics (MD) simulations. Thermal conductivity results are found to be very sensitive to the time step used in the simulations. For a time step of 0.1 fs, the converged thermal conductivity is 0.35 W/mK. Additionally the anisotropic thermal conductivity of a specially-modeled natural rubber model with straight molecular chains was studied and values of thermal conductivity parallel to the molecular chains was found to be 1.71 W/mK and the anisotropy, 2Kz/(Kx + Ky), was 2.67. PMID- 26353572 TI - Validity of the Taylor-Sedov Theory for Studying Laser-Induced Phase Explosion and Shock Waves. AB - Phase explosion is a phase change process that occurs during short pulse laser ablation. Phase explosion is a result of homogeneous nucleation of vapor in the superheated melt and results in a rapid transition from a superheated melt to a mixture of vapor and liquid droplets that expand from the surface. The sudden phase transition results in rapid material removal, and if occurring in an ambient gas, causes a shock wave to propagate away from the surface. Measurements of this shock wave are commonly used with the Taylor-Sedov blast wave theory to estimate shock wave pressure and temperature. At low laser fluences the Mach number of the shock wave can be small, resulting in significant errors in pressure and temperature. The paper will demonstrate conditions for which the more general form of the Rankine-Hugoniot relations for thermo-fluid parameters simplifies to the Taylor-Sedov similarity solutions and when the Taylor-Sedov solutions are applicable. The results are compared to experimental shock wave data from the literature to explain why using the Taylor-Sedov blast wave solutions can result in large errors at low Mach numbers. PMID- 26353573 TI - Novel Positive Temperature Coefficient Effect of Electrical Resistivity in Ni Particles Filled Two Semi-Crystalline Polymer Intermixture Nanocomposite. AB - A novel positive temperature coefficient (PTC) effect nanocomposite by employing both of polyvinylidene fluoride (PP) and polypropylene (PVDF) intermixture in 1-1 volume ratio as host materials and Ni nanoparticles as conductive filler was prepared via a simple hot compaction method. This study focused on the effect of Ni content on percolation threshold and temperature dependence of direct current (DC) resistivity, as well as frequency dependence of alternating current (AC) resistivity of nanocomposites. This kind of material showed a very small percolation threshold value (about 6.0 vol% of Ni) and a novel strong PTC effect of electrical resistivity between temperatures ranging 150-167 degrees C, which coincided with the both melting temperatures of PP and PVDF. Close to the percolation threshold, abnormal electrical behavior was observed and interpreted based on the tunnel conductivity between Ni clusters. The curves of the AC resistivity versus the frequency, at different loadings of Ni and at different temperatures, offered a further image of the arrangement of conducting clusters within the host. PMID- 26353574 TI - Monte Carlo Study on Carbon-Gradient-Doped Silica Aerogel Insulation. AB - Silica aerogel is almost transparent for wavelengths below 8 um where significant energy is transferred by thermal radiation. The radiative heat transfer can be restricted at high temperature if doped with carbon powder in silica aerogel. However, different particle sizes of carbon powder doping have different spectral extinction coefficients and the doped carbon powder will increase the solid conduction of silica aerogel. This paper presents a theoretical method for determining the optimal carbon doping in silica aerogel to minimize the energy transfer. Firstly we determine the optimal particle size by combining the spectral extinction coefficient with blackbody radiation and then evaluate the optimal doping amount between heat conduction and radiation. Secondly we develop the Monte Carlo numerical method to study radiative properties of carbon-gradient doped silica aerogel to decrease the radiative heat transfer further. The results indicate that the carbon powder is able to block infrared radiation and thus improve the thermal insulating performance of silica aerogel effectively. PMID- 26353575 TI - Carbon Nanotube/Cu Nanowires/Epoxy Composite Mats with Improved Thermal and Electrical Conductivity. AB - Polymer composites with carbon nanofillers have been regarded as a promising candidate for electronic package materials. The challenge for such materials is to increase the electrical and thermal conductivity of the composites. Herein, we reported an epoxy composite film with high thermal and electrical conductivity that were prepared by loading high volume fraction of well-dispersed multi-walled carbon nanotubes (MWCNTs, around 50 nm in diameter, 1-10 um in length) and copper nanowires (Cu NWs, 60-70 nm in diameter, 1-5 um in length) in epoxy matrix. The MWCNT-Cu NW hybrid mats were prepared by a vacuum filtration method with an optimum Cu NW content of 50 wt%. The hybrid mats was then impregnated by epoxy solution to prepare epoxy composite films. The epoxy was modified by the toughening agent to make the composite films tough and flexible. The loading fraction of MWCNTs and Cu NWs was tuned by controlling the viscosity of epoxy solution. A remarkable synergetic effect between the MWCNTs and Cu NWs in improving the electrical and thermal conductivity of epoxy composites was demonstrated. The results showed that the electrical conductivity of nanocomposites with 42.5 wt% epoxy was 1500 S/m, and the thermal conductivity was 2.83 W/m K, which was 10.1 times of the neat epoxy. Its thermal resistance was as low as 1% of the pure epoxy. And the mechanical properties of composites were also investigated. These robust and flexible nanocomposites showed prospective applications as thermal interface materials (TIMs) in the electronic industry. PMID- 26353576 TI - Stability of TiO2 Nanoparticles in Deionized Water with ZrP Nanoplatelets. AB - The stability of nanofluid is an important property that needs to be researched. In our study, a novel method using Zirconium phosphate (ZrP) discotic colloid to disperse nanoparticles was proposed for improving stability. TiO2 nanofluid was prepared by dispersing TiO2 nanoparticles into exfoliated a-ZrP suspensions at different concentrations. Scanning electron microscopy and X-ray diffraction were used to characterize the shape, average size, and components of primary ZrP nanoplatelets. The absorbance of the suspensions was measured by a UV-VIS spectrophotometer. The results show that the stability first increased, and then decreased with increasing ZrP concentration at 1 wt.% TiO2. The effect was optimal at 2 wt.% ZrP. Thus, the hindrance of nanoplatelets in the aggregation and sedimentation of nanoparticles is the main reason for improving the stability of nanofluids. PMID- 26353577 TI - Thermal Properties of Phase Change Composites Containing Ferric Oxide Nanoparticles. AB - We prepared a series of homogeneous nanocomposites by suspending Fe2O3 nanoparticles into paraffin wax (PW) matrix. Fe2O3/PW nanocomposites have reduced both solid-solid phase change latent heat capacity (Ls-s) and solid-liquid phase change latent heat capacity (Ls-l) with an increase in the mass fraction of Fe2O3 nanoparticles. There is almost equable solid-solid phase change temperature (Ts s) between PW and Fe2O3/PW composites, as well as melting temperature (Ts-l). Fe2O3 nanoparticle addition leads to substantial enhancement in the thermal conductivity of Fe2O3/PW and the enhancement ratio increases with the nanoparticle loading. Thermal conductivity of Fe2O3/PW composite with 3.0 wt% nanoparticles is about 0.27 W/(m . K) at 15 degrees C, which close to that of gamma-Al2O3/PW with 5.0 wt% nanoparticles but higher than that of ZnO/PW containing 5.0 wt% nanoparticles. At 60 degrees C, Fe2O3/PW has higher thermal conductivity than gamma-A12O3/PW and ZnO/PW contained with same fraction of nanoparticles. PMID- 26353578 TI - Electrochemical Performance of Graphene Oxide/Polyaniline Composite for Supercapacitor Electrode. AB - Composite film of graphene oxide (GO) and polyaniline (PANI) nanofibers is synthesized by in situ polymerization of aniline monomer in the GO suspension (GO/PANI composite). The morphology of the composite is examined by scanning electron microscopy (SEM) and transition electron microscopy (TEM). GO nanosheets are homogeneously coated by PANI nanofibers with diameter of 45 nm. Electrochemical performances are characterized by cyclic voltammetry (CV) and galvanostatic charge/discharge techniques. Supercapacitors based on the GO/PANI conductive composite exhibit high specific capacitance (676 F/g) at a discharge current density of 1.0 A/g in 1 M H2SO4 solution, which is much higher than PANI electrode (230 F/g). The excellent performance is attributed to the synergetic effect of GO and PANI nanofibers, which can shorten ion diffusion length and make higher materials utilization. Moreover, the composite electrode presents excellent long cycle life during charge/discharge processes. After 1000 cycles, the specific capacitance decreases 9% of initial capacitance compared to 32% for PANI nanofibers. This technique provides a feasible solution for developing high performance electrical energy storage devices. PMID- 26353579 TI - Ternary Mixed Crystal Effects on the Interface Optical Phonon Spectrum in Wurtzite GaN/AlxGa1-xN Quantum Wells. AB - Based on the dielectric continuum model and modified random-element isodisplacement model, the ternary mixed crystal effects on interface optical phonon and electron-interface optical coupling in GaN/AlxGa1-xN quantum wells are studied in a fully numerical manner. When the aluminium concentration in the range (0.03, 0.13), there exist two branches of interface optical phonons in high frequency range. When the aluminium concentration in the range (0.13, 1.00), there are four branches of interface optical phonons in high and low frequency range. With the increase of aluminium concentration, the frequencies of interface optical phonon almost change linearly. The electron-phonon couplings also almost linearly vary with aluminium concentration in high frequency range. But in low frequency range, the electron-phonon coupling indicate nonlinear changes with increasing aluminium concentration. PMID- 26353580 TI - Thermal Characterization of Lauric-Stearic Acid/Expanded Graphite Eutectic Mixture as Phase Change Materials. AB - The eutectic mixture of lauric acid (LA) and stearic acid (SA) is a desirable phase change material (PCM) due to the constant melting temperature and large latent heat. However, its poor thermal conductivity has hampered its broad utilization. In the present study, pure LA, SA and the mixtures with various mass fractions of LA-SA were used as the basic PCMs, and 10 wt% expanded graphite (EG) was added to enhance the thermal conductivities. The phase change behaviors, microstructural analysis, thermal conductivities and thermal stabilities of the mixtures of PCMs were investigated by differential scanning calorimetry (DSC), scanning electronic microscope (SEM), transient plane source (TPS) and thermogravimetric analysis (TGA), respectively. The results show that the LA-SA binary mixture of mixture ratio of 76.3 wt%: 23.7 wt% forms an eutectic mixture, which melts at 38.99 degrees C and has a latent heat of 159.94 J/g. The melted fatty acids are well absorbed by the porous network of EG and they have a good thermal stability. Furthermore, poor thermal conductivities can be well enhanced by the addition of EG. PMID- 26353581 TI - Formability and Magnetocaloric Effect of a Gd27.5La27.5Al20Co20Fe5 Bulk Metallic Glass. AB - A Gd27.5La27.5Al20Co20Fe5 bulk metallic glass (BMG) was synthesized by replacing 50% of the Gd element with the relatively cheap La element. The BMG has a rather high glass forming ability and the predicted critical diameter is about 7 mm by the differential scanning calorimetry (DSC) measurements. The BMG exhibits a medium range of refrigerant capacity (RC). The replacement of Gd with La leads to a slight reduction of the corresponding refrigerant efficiency of the alloy. However, the high value of magnetic entropy changes (-DeltaS(m)peak) and low cost still indicates that the Gd27.5La27.5Al20Co20Fe5 BMG can be regarded as a good magnetic refrigerant candidate. PMID- 26353582 TI - The Calculation of Thermal Conductivities by Three Dimensional Direct Simulation Monte Carlo Method. AB - Three dimensional direct simulation Monte Carlo (DSMC) method with the variable soft sphere (VSS) collision model is implemented to solve the Boltzmann equation and to acquire the heat flux between two parallel plates (Fourier Flow). The gaseous thermal conductivity of nitrogen is derived based on the Fourier's law under local equilibrium condition at temperature from 270 to 1800 K and pressure from 0.5 to 100,000 Pa and compared with the experimental data and Eucken relation from Chapman and Enskog (CE) theory. It is concluded that the present results are consistent with the experimental data but much higher than those by Eucken relation especially at high temperature. The contribution of internal energy of molecule to the gaseous thermal conductivity becomes significant as increasing the temperature. PMID- 26353583 TI - Engineering of Biocompatible pH-Responsive Nanovehicles from Acetalated Cyclodextrins as Effective Delivery Systems for Tumor Therapy. AB - There is still an unmet demand for materials with excellent biocompatibility, controlled hydrolytic capability, and elegant responsiveness to chemical or physical stimuli. To engineer biocompatible materials from beta-cyclodextrin (beta-CD), in this study, we synthesized acetalated beta-CDs (Ac-betaCDs) by one pot acetalation using 2-ethoxypropene as an acetonation reagent, which can be further processed into nanoparticles (NPs) via the emulsion technique. Ac-betaCD NPs showed pH-labile hydrolysis and pH-triggered release of docetaxel (DTX) payload. Both properties were mainly dominated by the molar ratio of linear to cyclic acetal, which can be conveniently modulated by the acetalation time used for materials synthesis. Ac-betaCD NPs were found to be biocompatible in both in vitro cell culture and in vivo acute toxicity evaluations following intravenous injection. In vitro cell culture experiments demonstrated that antitumor activity of DTX against both sensitive and resistant cancer cells was remarkably improved by formulation into Ac-betaCD nanomedicines. In vivo antitumor study also substantiated the dramatically enhanced efficacy of DTX/Ac-betaCD NPs in a melanoma-bearing nude mouse model. These studies demonstrated that NPs derived from Ac-betaCDs may serve as biocompatible and effective carriers for drug delivery. PMID- 26353584 TI - Biocompatible and Antibacterial SnO2 Nanowire Films Synthesized by E-Beam Evaporation Method. AB - In this work, the biocompatibility and antibacterial activities of novel SnO2 nanowire coatings prepared by electron-beam (E-Beam) evaporation process at low temperatures were studied. The nanowire coatings were characterized by scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDX), and X-ray diffraction (XRD) methods. The results of in vitro cytotoxicity and cell proliferation assays suggested that the SnO2 nanowire coatings were nontoxic and promoted the proliferation of C2C12 and L929 cells (> 90% viability). Cellular activities, cell adhesion, and lactate dehydrogenase activities were consistent with the superior biocompatibility of the nanowire materials. Notably, the nanowire coating showed potent antibacterial activity against six different bacterial strains. The antibacterial activity of the SnO2 material was attributed to the photocatalytic nature of SnO2. The antibacterial activity and biocompatibility of the newly developed SnO2 nanowire coatings may enable their use as coating materials for biomedical implants. PMID- 26353585 TI - Imaging and Chemotherapeutic Comparisons of Iron Oxide Nanoparticles Chemically and Physically Coated with Poly(ethylene glycol)-b-Poly(epsilon-caprolactone)-g Poly(acrylic acid). AB - We designed a new copolymer, poly(ethylene glycol)-block-poly(epsilon caprolactone)-graft-poly(acrylic acid) (PAA-PEC), which could be chemically and physically coated onto iron oxide (Fe3O4) nanoparticles for theranostic applications. The chemically PAA-PEC-coated Fe3O4 nanoparticles (PAA-PEC-IO) were prepared using the carboxylic groups of PAA-PEC to bind the Fe3O4 nanoparticles during a co-precipitation reaction. Because of the amphiphilic properties of PAA PEC, the compound self-assembled into a core-shell structure. The hydrophobic oleic acid-coated Fe3O4 nanoparticles could then be physically encapsulated inside the hydrophobic core of PAA-PEC (PAA-PEC-OA-IO) using an emulsion technique. A similar amount of iron content was controlled in both the PAA-PEC-IO and PAA-PEC-OA-IO (-23%). The particle diameters, morphologies, superparamagnetism, drug loading efficiency, and transversal relaxivity (r2) were studied and compared between the two magnetic nanoparticles. All results displayed the chemically-synthesized PAA-PEC-IO nanoparticles had higher potential than did the physically-synthesized PAA-PEC-OA-IO as an MRI contrast agent and a drug delivery carrier. Rodamine123-linked PAA-PEC-IO (PAA-PEC-IO Rh123) was used as a molecular probe. Flow cytometric diagrams indicated that cellular internalization of PAA-PEC-IO occurred primarily through clathrin mediated endocytosis. PMID- 26353586 TI - PEGylated Dendrimer-Doxorubicin Cojugates as pH-Sensitive Drug Delivery Systems: Synthesis and In Vitro Characterization. AB - To achieve liver-specific delivery of antitumor drug doxorubicin (DOX), PEGylated dendrimer-DOX conjugates were designed and synthesized, whereas DOX was conjugated to dendrimers via hydrazone bonds and the dendrimers were functionalized with galactose moieties. The release rates of DOX from the conjugates at pH 5.0 were much faster than those at pH 7.4 due to the pH sensitive cleavage of the hydrazone bonds. The conjugates were shown to effectively kill HepG2 cells in vitro. Compared to other conjugates, the PEGylated dendrimer-DOX one with multiple galactose moieties (Dendrimer-DOX-PEG Gal) demonstrated HepG2 cells specificity, higher efficacy and good biosafety due to the lower IC50 value and higher cellular uptake confirmed by in vitro cytotoxicity assays, confocal laser scanning microscopy and flow cytometric studies. These results suggest that Dendrimer-DOX-PEG-Gal is an efficient and biocompatible candidate for the specific delivery of antitumor drug to HepG2 cells and could be used as liver cancer specific drug delivery system. PMID- 26353587 TI - Remote-Controlled DNA Release from Fe3O4@Au Nanoparticles Using an Alternating Electromagnetic Field. AB - We demonstrated a remote-controlled DNA release strategy, in which irradiation of nanoparticles with an alternating electromagnetic field (AMF) results in DNA release on demand. The method we developed used 6-carboxyfluorescein (FAM) labeled diblock DNA to modify Fe3O4@Au nanoparticles (NPs) through the affinity of adenine with the surfaces of the NPs. The DNA release was confirmed by zeta potential measurement, surface-enhanced Raman scattering spectroscopy, gel electrophoresis, and fluorescence spectroscopy. The experimental results showed that the DNA was released into the surrounding medium under irradiation with an AMF at a frequency of 20-25 kHz. The DNA release was efficient (60%-70%), and externally controllable by tuning various parameters, such as the sequences length of the diblock DNA, the pH value of environmental solutions, and the power and the time of AMF irradiation. Furthermore, the AMF-triggered DNA release was successfully performed in human cervical cancer (HeLa) cells, demonstrating the system's ability to maintain the release behavior in vitro. This remote controlled DNA release method presents a new application for DNA-modified NPs in targeted therapies. PMID- 26353588 TI - ZnO Nanorod-Based Non-Enzymatic Optical Glucose Biosensor. AB - The highly sensitive, interference-free and non-enzymatic optical sensing of glucose has been made possible for the first time using the hydrothermally synthesized ZnO nanorods. The UV irradiation of glucose-treated ZnO nanorods decomposes glucose into hydrogen peroxide (H2O2) and gluconic acid by UV oxidation. The ZnO nanorods play the role of a catalyst similar to the oxidase used in the enzymatic glucose sensors. The photoluminescence (PL) intensity of the near-band edge emission of the ZnO nanorods linearly decreased with the increased concentration of H2O2. Therefore, the glucose concentration is monitored over the wide range of 0.5-30 mM, corresponding to 9-540 mg/dL. The concentration range of the linear region in the calibration curve is suitable for its clinical use as a glucose sensor, because the glucose concentration of human serum is typically in the range of 80-120 mg/dL. In addition, the optical glucose sensor made of the ZnO nanorods is free from interference by bovin serum albumin, ascorbic acid or uric acid, which are also present in human blood. The non enzymatic ZnO-nanorod sensor has been demonstrated with human serum samples from both normal persons and diabetic patients. There is a good agreement between the glucose concentrations measured by the PL quenching and standard clinical methods. PMID- 26353589 TI - Co-Encapsulation of Combretastatin-A4 Phosphate and Doxorubicin in Polymersomes for Synergistic Therapy of Nasopharyngeal Epidermal Carcinoma. AB - In this study, we designed biodegradable polymersomes for co-delivery of an antiangiogenic drug combretastatin-A4 phosphate (CA4P) and doxorubicin (DOX) to collapse tumor neovasculature and inhibit cancer cell proliferation with the aim to achieve synergistic antitumor effects. The polymersomes co-encapsulating DOX and CA4P (Ps-DOX-CA4P) were prepared by solvent evaporation method using methoxy poly(ethylene glycol)-b-polylactide (mPEG-PLA) block copolymers as drug carriers. The resulting Ps-DOX-CA4P has vesicles shape with uniform sizes of about 50 nm and controlled co-encapsulation ratios of DOX to CA4P. More importantly, Ps-DOX CA4P (1:10) showed strong synergistic cytotoxicity (combination index CI = 0.31) against human nasopharyngeal epidermal carcinoma (KB) cells. Furthermore, Ps-DOX CA4P accumulated remarkably in KB tissues xenografts in nude mice. Consistent with these observations, Ps-DOX-CA4P (1:10) achieved significant antitumor potency because of fast tumor vasculature disruption and sustained tumor cells proliferation inhibition in vivo. The overall findings indicate that co-delivery of an antiangiogenic drug and a chemotherapeutic agent in polymersomes is a potentially promising strategy for cancer therapy. PMID- 26353590 TI - A Titanium Surface-Modified with Nano-Sized Hydroxyapatite and Simvastatin Enhances Bone Formation and Osseintegration. AB - The aim of the present study was to evaluate whether coating pristine titanium (Ti) with nano-sized hydroxyapatite (HAp) and simvastatin could enhance bone formation and osseointegration in vitro and in vivo because both HAp and simvastatin have the characteristic of osteogenetic induction. Pristine Ti was sequentially surface-treated with NaOH, 1,1-carbonyldiimidazole (CDI), beta cyclodextrin-immobilized HAp powders (beta-CD/HAp), and simvastatin before analysis using scanning electron microscopy (SEM), X-ray photoelectron microscopy (XPS), and static contact angle measurement. This revealed that simvastatin was released continually for up 28 days. Modification of the Ti surface with nano sized HAp and simvastatin (Ti/beta-CD/HAp/Sim) discs enhanced the osteogenic differentiation of MC3T3-E1 cells in vitro. Furthermore, Ti/beta-CD/HAp/Sim of screw type enhanced bone formation between the screw and the host bone when the screw implanted to the proximal tibia and femoral head of rabbits. These results suggest that surface modification of nano-sized HAp and simvastatin are effective tools for developing attractive dental implants. PMID- 26353591 TI - A Strategy for Accurate Quantification of 5-Methylcytosine and 5 Hydroxymethylcytosine at CpG Sites Within Gene Promoter. AB - 5-Methylcytosine (5mC) can be converted to 5-hydroxymethylcytosine (5hmC) in mammalian DNA by the ten-eleven translocation (TET) enzymes. Traditional bisulfite-based DNA methylation analysis techniques have been widely used in the detection of 5mC. However, they can not discriminate 5hmC from 5mC, leading to overestimate 5mC levels. We here introduce a strategy, combination of selective oxidation and bisulfite pyrosequencing (BS-Pyroseq), for quantification of both 5mC and 5hmC at CpG sites within the promoters of CDH1, DAPK, RARbeta and RUNX3 genes in a panel of cell lines and clinical samples. As expected, oxidative bisulfite pyrosequencing (oxBS-Pyroseq) assay decreased overall or site-specific methylation levels of three of these genes in most cell lines as compared with BS Pyroseq assay. Similarly, decreased overall or site-specific methylation levels of DAPK, RARbeta and RUNX3 genes in laryngeal, gastric and thyroid cancer and their matched normal tissues, respectively, were also found by a comparison between these two techniques, particularly in cancerous tissues. In addition, by using this combined strategy and hydroxymethylcytosine DNA immunoprecipitation (hMeDIP) assay, we demonstrated that TET1 up-regulated DAPK expression through promoter demethylation. Collectively, this strategy is easy to establish and accurately discriminates and quantifies 5mC and 5hmC at CpG sites within selected gene promoters. PMID- 26353592 TI - 99mTc-Labeled Iron Oxide Nanoparticles for Dual-Contrast (T1/T2) Magnetic Resonance and Dual-Modality Imaging of Tumor Angiogenesis. AB - Multi functional probes possessing magnetic resonance imaging and single-photon emission computed tomography properties are favorable for the molecular imaging of cancers. In this study, ultra small super paramagnetic iron oxide nanoparticles, about 3.5 nm in size, were synthesized by the polyol method. The particles were functionalized using c(RGDyC) peptides and labeled with 99mTc to prepare molecular imaging probes for detecting tumor angiogenesis. The probes demonstrated good T1 (r1 = 8.2 s(-1) mM(-1)) and reasonable T2 contrast effects (r2 = 20.1 s(-1) mM(-1)) and could specifically target avbeta3-positive cells, inducing more cell ingestion, unlike that in case of the control probes [functionalized with scrambled c(RADyC) peptides]. After the probes were injected into the mice bearing H1299 lung tumors, T1/T2-weighted magnetic resonance imaging and single-photon emission computed tomography revealed that they addressed tumor angiogenic vessels, which were distributed mainly in the peripheral region of tumors. Biodistribution studies indicated that tumor accumulation of the probes was significant [13.8 +/- 9.6%ID/g (p < 0.01), which is more than that of the control probes, 4.5 +/- 1.9%ID/g], and could be inhibited by free RGD peptides (6.0 +/- 2.8%ID/g, p < 0.01). Our study demonstrated that the dual-contrast (T1/T2) magnetic resonance and dual-modal imaging probe based on ultra small superparamagnetic iron oxide nanoparticles is very promising for the molecular imaging of tumor angiogenesis. PMID- 26353593 TI - Local Administration of Gold Nanoparticles Prevents Pivotal Pathological Changes in Murine Models of Atopic Asthma. AB - Although gold nanoparticles have been shown to exhibit a range of beneficial biological properties, including antiinflammatory and anti-oxidant effects, their putative impact on allergic asthma has not been addressed. In this study, we evaluated the potential of nasal-instilled gold nanoparticles to prevent allergen induced asthma in distinct murine models of this disease. Swiss-Webster (outbred) and A/J (inbred) mice were sensitized with ovalbumin and then treated with intranasal injections of gold nanoparticles (6 and 60 MUg/kg), 1 h before ovalbumin challenges. Lung function, leukocyte infiltration, mucus exacerbation, extracellular matrix deposition, cytokine generation and oxidative stress were evaluated 24 h after the last challenge. In both mice strains, gold nanoparticles clearly inhibited (70-100%) allergen-induced accumulation of inflammatory cells as well as the production of both pro-inflammatory cytokines and reactive oxygen species. In A/J mice, recognized as genetic asthma prone animals, instilled gold nanoparticles clearly prevented mucus production, peribronchiolar fibrosis and airway hyper-reactivity triggered by allergen provocation. In conclusion, these findings demonstrate that gold nanoparticles prevented pivotal features of asthma, including airway hyper-reactivity, inflammation and lung remodelling. Such protective effects are accounted for by reduction in lung tissue generation of pro-inflammatory cytokines and chemokines, in a mechanism probably related to down-regulation in the levels of oxidative stress. PMID- 26353594 TI - Physical Property Control on the Cellular Uptake Pathway and Spatial Distribution of Nanoparticles in Cells. AB - Nanoparticles have been developed in broad biomedical research in terms of effective cellular interactions to treat and visualize diseased cells. Considering the charge and polar functional groups of proteins that are embedded in cellular membranes, charged nanoparticles have been strategically developed to enhance electrostatic cellular interactions. In this study, we show that cellular uptake efficiency, pathway, and spatial distribution of gold nanoparticles in a cell are significantly modulated based on the surface condition of gold nanoparticles and human cancer cells that were tuned by controlling the pH of the medium and by introducing an electron beam. Cellular uptake efficiency is increased when electrostatic attraction is induced between the cells and the gold nanoparticles. Cell surface modification changes the cellular uptake pathways of the gold nanoparticles and concentrates the gold nanoparticles at the membrane region. Surface modification of the gold nanoparticles also contributes to deep penetration and homogeneous spatial distributions in a cell. PMID- 26353595 TI - Interaction of Silver Nanoparticles with Triosephosphate Isomerase from Human and Malarial Parasite (Plasmodium falciparum): A Comparative Study. AB - Recombinant triosephosphate isomerase from Plasmodium falciparum (PfTIM) and humans (hTIM) were expressed, purified and characterised. High specific activity (1207 U x mg(-1)) with a fold purification of -1.8 and a yield of 48% were obtained for hTIM after gel filtration while, in contrast PfTIM afforded a specific activity of 1387 U x mg(-1) with a fold purification of -6.8 and a yield of 57% after gel filtration and prior to dialysis. PfTIM had an optimal pH and temperature, K(m) and V(max) of 5.25, 25 degrees C, 12.8 mM and 1.13 MUmol x mL( 1) min(-1) respectively while for hTIM the pH and temperature optima, K(m) and V(max) were 6.75, 30 degrees C; 8.2 mM and 1.35 MUmol x ml(-1) min(-1). Polyvinylpyrrolidone stabilised silver nanoparticles (60 nM; 2-6 nm diameter) selectively inhibited PfTIM with a 7-fold decrease in enzyme catalytic efficiency (K(cat)/K(m)) over hTIM. Respective K(i) values were 283 nM [hTIM] and 85.7 nM [PfTIM]. Key structural differences between the two enzyme variants, especially with Cys13 at the dimer interface of PfTIM, were significant enough to suggest unique characteristics allowing for selective targeting of PfTIM by AgNPs. PMID- 26353596 TI - Endothelial Cell Growth and Differentiation on Collagen-Immobilized Polycaprolactone Nanowire Surfaces. AB - The success of cardiovascular implants is associated with the development of an endothelium on material surface, critical to the prevention of intimal hyperplasia, calcification and thrombosis. A thorough understanding of the interaction between vascular endothelial cells and the biomaterial involved is essential in order to have a successful application which promotes healing and regeneration through integration with native tissue. In this study, we have developed collagen immobilized nanostructured surfaces with controlled arrays of high aspect ratio nanowires for the growth and maintenance of human microvascular endothelial cells (HMVECs). The nanowire surfaces were fabricated from polycaprolactone using a novel nanotemplating technique, and were immobilized with collagen utilizing an aminolysis method. The collagen immobilized nanowire surfaces were characterized using contact angle measurements, scanning electron microscopy and X-ray photoelectron spectroscopy. Human microvascular endothelial cells were used to evaluate the efficacy of the collagen immobilized nanowire surfaces to promote cell adhesion, proliferation, viability and differentiation. The results presented here indicate significantly higher cellular adhesion, proliferation and viability on nanowire and collagen immobilized surfaces as compared to the control surface. Further, HMVECs have a more elongated body and low shape factor on nanostructured surfaces. The differentiation potential of collagen immobilized nanowire surfaces was also evaluated by immunostaining and western blotting for key endothelial cell markers that are expressed when human microvascular endothelial cells are differentiated. Results indicate that expression of VE-cadherin is increased on collagen immobilized surfaces while the expression of von Willebrand factor is statistically similar on all surfaces. PMID- 26353597 TI - Fabrication of Curcumin Micellar Nanoparticles with Enhanced Anti-Cancer Activity. AB - Although curcumin is effective in killing cancer cells, its low water solubility and inadequate bioavailability remain major limitations to its therapeutic application. Formulating curcumin micellar nanoparticles (Cur-NPs) encapsulated with a biodegradable polymer can significantly improve curcumin's solubility, stability, and bioavailability in vitro. In this study, differently sized Cur-NPs coated with polyvinyl alcohol (PVA) were engineered. The particle size, encapsulation efficiency, in vitro release, stability, cytotoxicity, and cellular uptake of these Cur-NPs were characterized in several cancer cell lines. The results showed that, relative to solubilized curcumin, Cur-NPs demonstrated higher cytotoxicity against cancer cells. To our knowledge, this study is the first to demonstrate that the extent of the anti-cancer potency and cellular uptake of Cur-NPs is directly correlated to particle size, where Cur-NPs with the smallest size (28 nm) were the most potent. Confocal microscopy revealed the subcellular localization of the smaller Cur-NPs (28 nm) to be in both the nucleus and cytoplasm, while the larger particles (200 nm) were only localized in the cytoplasm. PMID- 26353598 TI - Visible-Light Nanostructured Photocatalysts--A Review. AB - This paper reviews the recent research and development of novel visible-light induced photocatalysts with nanostructures. In recent years, Ag3PO4-based and BiVO4-based nanomaterials have drawn wide attention due to their narrow band gap and excellent photocatalytic performance. The development of the new material covers the synthesis condition, unique morphology, further modification which focused on the Ag3PO4 and BiVO4, respectively. Meanwhile, titanium dioxide has already become one of the classical photocatalyst. However, the band gap of TiO2 (3.2 eV) limits its efficient utilization of solar energy, two categories novel modification methods of TiO2 are proposed to make them active under visible light illumination. Using polymers and dye to modify TiO2 is a wonderful approach to achieve excellent electronic and optical properties mainly in aspect of photocatalytic application. Therefore, the paper summarizes novel nanosized photocatalysts with visible-light response including Ag3PO4-based, BiVO4-based and TiO2-based materials, and suggests the further research prospect for the visible-light induced photocatalysts. PMID- 26353599 TI - Fabrication and Characterization of Molecular Electronic Devices. AB - The concept of molecular electronic devices is utilizing single molecules or molecular monolayers as active electronic components. Rapid advances in technology have enabled us to engineer molecular electronic devices with diverse functionalities. This review article emphasizes on experimental aspects of electronic devices made with single molecules or molecular monolayers, with a primary focus on the characterization and manipulation of charge transport. PMID- 26353600 TI - Applications of Titania Nanotubes in Bone Biology. AB - Orthopedic implants, including artificial joints and fracture fixation devices, have helped to restore the physical independence of many patients, thereby improving the quality of their lives. Titania (Ti) and its alloys are better implant materials than stainless steel and Co-Cr alloys owing to their superior mechanical properties and biocompatibility; however, Ti-based implants may sometimes fail, leading to repeated surgeries. With the recent advancements in nanotechnology, the nanosurface modifications of Ti, especially in the form of Ti nanotubes (TNTs), have drastically improved the properties of orthopedic implants. In this review, we have summarized the fabrication of Ti nanotubes by electrochemical anodization and their influence on osteoblast cells and staphylococcus aureus. In addition, we have discussed the corrosion resistance of Ti nanotubes. PMID- 26353601 TI - A Special Section on Nanodiamonds for Biomedical Applications. PMID- 26353602 TI - Nanodiamond-Based Composite Structures for Biomedical Imaging and Drug Delivery. AB - Nanodiamond particles are widely recognized candidates for biomedical applications due to their excellent biocompatibility, bright photoluminescence based on color centers and outstanding photostability. Recently, more complex architectures with a nanodiamond core and an external shell or nanostructure which provides synergistic benefits have been developed, and their feasibility for biomedical applications has been demonstrated. This review is aimed at summarizing recent achievements in the fabrication and functional demonstrations of nanodiamond-based composite structures, along with critical considerations that should be taken into account in the design of such structures from a biomedical point of view. A particular focus of the review is core/shell structures of nanodiamond surrounded by porous silica shells, which demonstrate a remarkable increase in drug loading efficiency; as well as nanodiamonds decorated with carbon dots, which have excellent potential as bioimaging probes. Other combinations are also considered, relying on the discussed inherent properties of the inorganic materials being integrated in a way to advance inorganic nanomedicine in the quest for better health-related nanotechnology. PMID- 26353603 TI - Biomedical Applications of Nanodiamonds: An Overview. AB - Nanodiamonds are a novel class of nanomaterials which have raised much attention for application in biomedical field, as they combine the possibility of being produced on large scale using relatively inexpensive synthetic processes, of being fluorescent as a consequence of the presence of nitrogen vacancies, of having their surfaces functionalized, and of having good biocompatibility. Among other applications, we mainly focus on drug delivery, including cell interaction, targeting, cancer therapy, gene and protein delivery. In addition, nanodiamonds for bone and dental implants and for antibacterial use is discussed. Techniques for detection and imaging of nanodiamonds in biological tissues are also reviewed, including electron microscopy, fluorescence microscopy, Raman mapping, atomic force microscopy, thermal imaging, magnetic resonance imaging, and positron emission tomography, either in vitro, in vivo, or ex vivo. Toxicological aspects related to the use of nanodiamonds are also discussed. Finally, patents, preclinical and clinical trials based on the use of nanodiamonds for biomedical applications are reviewed. PMID- 26353604 TI - Functionalized Nanodiamonds for Biological and Medical Applications. AB - Nanodiamond is a promising material for biological and medical applications, owning to its relatively inexpensive and large-scale synthesis, unique structure, and superior optical properties. However, most biomedical applications, such as drug delivery and bio-imaging, are dependent upon the precise control of the surfaces, and can be significantly affected by the type, distribution and stability of chemical funtionalisations of the nanodiamond surface. In this paper, recent studies on nanodiamonds and their biomedical applications by conjugating with different chemicals are reviewed, while highlighting the critical importance of surface chemical states for various applications. PMID- 26353605 TI - Luminescent Diamond Nanoparticles: Physical, Chemical and Biological Aspects of the Phenomenon. AB - Biosensors based on nanodiamonds are able to penetrate through the cell membrane in a targeted manner and probe changes in real-time in the inner cellular space. In this work we performed exclusive theoretical and experimental study of nanodiamond particles adjusted for application in optically-traceable intracellular nanodiamond sensors. Theoretical and experimental study of specific optical properties of high-pressure high-temperature nanodiamonds containing NV- and NV0 centres were performed. The results are supported by theoretical modeling. The final result of this study was detection of luminescence ND in living cells and in vivo application od luminiscence NDs in chicken embryo, showing the detectability of luminescence ND using a standard confocal microscope. On the level of in cells selectivity numerous clusters of ND particles were present within the cytoplasm and at the same time no particles were absent in the nucleus-ND particles can be used as imaging or delivery system for specific cell parts targeting. From our study we can say that biosensors based on nanodiamonds (NDs) are able to penetrate through the cell membrane in a targeted manner and probe changes in the inner cellular space. PMID- 26353606 TI - Nanostructured Diamond Device for Biomedical Applications. AB - Diamond is increasingly used in biomedical applications because of its unique properties such as the highest thermal conductivity, good optical properties, high electrical breakdown voltage as well as excellent biocompatibility and chemical resistance. Diamond has also been introduced as an excellent substrate to make the functional microchip structures for electrophoresis, which is the most popular separation technique for the determination of analytes. In this investigation, a diamond electrophoretic chip was manufactured by a replica method using a silicon mold. A polycrystalline 300 micron-thick diamond layer was grown by the microwave plasma-assisted CVD (MPCVD) technique onto a patterned silicon substrate followed by the removal of the substrate. The geometry of microstructure, chemical composition, thermal and optical properties of the resulting free-standing diamond electrophoretic microchip structure were examined by CLSM, SFE, UV-Vis, Raman, XRD and X-ray Photoelectron Spectroscopy, and by a modified laser flash method for thermal property measurements. PMID- 26353607 TI - Optically Detected Magnetic Resonance of Nanodiamonds In Vivo; Implementation of Selective Imaging and Fast Sampling. AB - Single-molecule fluorescence measurements of biological samples frequently suffer from background autofluorescence originating from fluorescent materials pre existing in living samples, and from unstable photo-physical properties of fluorescent labeling molecules. In this study, we first describe our method of selective imaging of nanodiamonds containing nitrogen-vacancy centers, promising fluorescent color centers, by a combination of optically detected magnetic resonance. The resultant images exhibit perfect elimination of extraneous fluorescence in real-time microscope observations. As the practical example applied to an in vivo system, we measured the resonance spectrum of nanodiamonds introduced into the intestine of Caenorhabditis elegans in the clear background and compared the spectral profile over time. The observed evolution strongly suggests that the rotation of the nanodiamond was detected. We also report our recent progress in the development of a spectrometer equipped with an avalanche photo-diode for fast sampling of photons, which can be used while observing the selective image of a field of view in a real-time manner. This apparatus is suitable for exploring dynamics through the measurement of fluctuation in fluorescence intensity caused by a rotating nanodiamond. PMID- 26353608 TI - Rhodamine/Nanodiamond as a System Model for Drug Carrier. AB - In this paper we present some strategies that are being developed in our labs towards enabling nanodiamond-based applications for drug delivery. Rhodamine B (RhB) has been choosen as model molecule to study the loading of nanodiamonds with active moieties and the conditions for their controlled release. In order to test the chemical/physical interactions between functionalized detonation nanodiamond (DND) and complex molecules, we prepared and tested different RhB@DND systems, with RhB adsorbed or linked by ionic bonding to the DND surface. The chemical state of the DND surfaces before conjugation with the RhB molecules, and the chemical features of the DND-RhB interactions have been deeply analysed by coupling DND with Au nanoparticles and taking advantage of surface enhanced Raman spectroscopy SERS. The effects due to temperature and pH variations on the process of RhB release from the DND carrier have been also investigated. The amounts of released molecules are consistent with those required for effective drug action in conventional therapeutic applications, and this makes the DND promising nanostructured cargos for drug delivery applications. PMID- 26353609 TI - Structure and Bonding in Chlorine-Functionalized Nanodiamond--Nuclear Magnetic Resonance and X-Ray Photoelectron Spectroscopy Study. AB - We report on investigation of detonation nanodiamond annealed at 800C degrees in chlorine atmosphere by means of 1H, 13C and 35Cl nuclear magnetic resonance and X ray photoelectron spectroscopy. The results of these methods are found to be consistent with each other and evidence formation of chlorine-carbon groups and sp2 carbon shell on the nanodiamond surface. The data obtained provide detailed information about the structure and bonding in this diamond nanoparticle. Interaction of nuclear spins with unpaired electron spins of dangling bonds results in fast 13C nuclear spin-lattice relaxation. PMID- 26353610 TI - Preparation and Characterization of Ion-Irradiated Nanodiamonds as Photoacoustic Contrast Agents. AB - Highly radiation-damaged or irradiated nanodiamonds (INDs) are a new type of nanomaterial developed recently as a potential photoacoustic (PA) contrast agent for deep-tissue imaging. This work characterized in detail the photophysical properties of these materials prepared by ion irradiation of natural diamond powders using various spectroscopic methods. For 40-nm NDs irradiated with 40-keV He+ at a dose of 3 x 10(15) ions/cm2, an average molar extinction coefficient of 4.2 M-1 cm-1 per carbon atom was measured at 1064 nm. Compared with gold nanorods of similar dimensions (10 nm x 67 nm), the INDs have a substantially smaller (by > 4 orders of magnitude) molar extinction coefficient per particle. However, the deficit is readily compensated by the much higher thermal stability, stronger hydrophilic interaction with water, and a lower nanobubble formation threshold (~30 mJ/cm2) of the sp3-carbon-based nanomaterial. No sign of photodamage was detected after high-energy (>100 mJ/cm2) illumination of the INDs for hours. Cell viability assays at the IND concentration of up to 100 ug/mL showed that the nanomaterial is non-cytotoxic and potentially useful for long-term PA bioimaging applications. PMID- 26353611 TI - Nanodiamonds of Laser Synthesis for Biomedical Applications. AB - In recent decade detonation nanodiamonds (DND), discovered 50 years ago and used in diverse technological processes, have been actively applied in biomedical research as a drug and gene delivery carrier, a contrast agent for bio-imaging and diagnostics and an adsorbent for protein separation and purification. In this work we report about nanodiamonds of high purity produced by laser assisted technique, compare them with DND and consider the prospect and advantages of their use in the said applications. PMID- 26353612 TI - Assessment of Carbon- and Metal-Based Nanoparticle DNA Damage with Microfluidic Electrophoretic Separation Technology. AB - In this study, we examined the feasibility of extracting DNA from whole cell lysates exposed to nanoparticles using two different methodologies for evaluation of fragmentation with microfluidic electrophoretic separation. Human lung macrophages were exposed to five different carbon- and metal-based nanoparticles at two different time points (2 h, 24 h) and two different doses (5 ug/ml, 100 ug/ml). The primary difference in the banding patterns after 2 h of nanoparticle exposure is more DNA fragmentation at the higher NP concentration when examining cells exposed to nanoparticles of the same composition. However, higher doses of carbon and silver nanoparticles at both short and long dosing periods can contribute to erroneous or incomplete data with this technique. Also comparing DNA isolation methodologies, we recommend the centrifugation extraction technique, which provides more consistent banding patterns in the control samples compared to the spooling technique. Here we demonstrate that multi-walled carbon nanotubes, 15 nm silver nanoparticles and the positive control cadmium oxide cause similar DNA fragmentation at the short time point of 2 h with the centrifugation extraction technique. Therefore, the results of these studies contribute to elucidating the relationship between nanoparticle physicochemical properties and DNA fragmentation results while providing the pros and cons of altering the DNA isolation methodology. Overall, this technique provides a high throughput way to analyze subcellular alterations in DNA profiles of cells exposed to nanomaterials to aid in understanding the consequences of exposure and mechanistic effects. Future studies in microfluidic electrophoretic separation technologies should be investigated to determine the utility of protein or other assays applicable to cellular systems exposed to nanoparticles. PMID- 26353613 TI - Development of Composite Poly(Lactide-co-Glycolide)- Nanodiamond Scaffolds for Bone Cell Growth. AB - There are relatively few nanotechnologies that can produce nanocomposite scaffolds for cell growth. Electrospinning has emerged as the foremost method of producing nanofibrous biomimetic scaffolds for tissue engineering applications. In this study diamond nanoparticles were integrated into a polymer solution to develop a nanocomposite scaffold containing poly(lactide-co-glycolide) (PLGA) loaded with diamond nanoparticles. To investigate the effect of adding diamond nanoparticles to PLGA scaffolds, primary human mesenchymal stem cells (hMSCs) were seeded on the scaffolds. The cytocompatibility results showed that addition of diamond nanoparticles did not impinge upon cell proliferation, nor was there a cytotoxic cellular response after 9 days in culture. Scanning electron microscopy, transmission electron microscopy, atomic force microscopy and confocal microscopy enabled qualitative characterization of the fibres and revealed cell morphology and number. Furthermore, surface roughness was measured to evaluate diamond nanoparticle modifications, and no significant difference was found between the diamond nanocomposite and pure polymer scaffolds. On the other hand, bright spots on phase images performed by atomic force microscopy suggested a higher hardness at certain points on fibers of the PLGA-nanodiamond composites, which was supported by nanoindentation measurements. This study shows that PLGA nanofibers can be reinforced with nanodiamond without adversely affecting cell behaviour, and thus it sets the foundation for future application of these scaffolds in bone tissue engineering. PMID- 26353614 TI - Biodistribution of Different Sized Nanodiamonds in Mice. AB - The particle size is one of critical parameters influencing the biodistribution of detonation nanodiamonds (DND) after their administration into the body. As DNDs are prone to aggregation, the difference between their sizes in aqueous and physiological solutions has to be taken into account. Radioactive I125-BSA molecules were covalently immobilized on DNDs divided in three fractions of different average size. The DND-BSAI125 conjugates were intravenously administrated into adult mice and the particle allocation in the animal's organs and blood was evaluated based on the radioactivity distribution. We conclude that most of the conjugates were taken from the bloodstream and trapped in the liver and spleen. The short-term distribution pattern for all DNDs was similar regardless of size and practically unchanged with time. No significant clearance of the particles was observed for 4 h, but the presence of DNDs was detected in the blood. It was found that the largest particles tend to accumulate more into the liver as compared to the smaller ones. However, the size effect was not well pronounced for the studied size range. PMID- 26353615 TI - Synthesis, Characterization, and Magnetic Resonance Evaluation of Polyglycerol Functionalized Detonation Nanodiamond Conjugated with Gadolinium(III) Complex. AB - A nanodiamond-polyglycerol-gadolinium(ll) conjugate has been designed and prepared as novel nanodiamond-based magnetic resonance (MR) contrast agent dispersible in physiological media. Detonation nanodiamond (dND) was first grafted with polyglycerol (PG) through ring-opening polymerization of glycidol to impart dispersibility to dND in physiological media. Since the hydroxyl group in PG serves as a scaffold for further surface functionalization, diethylenetriaminepentaacetic acid (DTPA) was immobilized on the surface of dND PG through multistep organic transformations and Gd(III) ion was complexed in the last step. The resulting dND-PG-Gd(III) exhibited good dispersibility (> 4.5 mg/mL) and stability (> 3 months) in phosphate buffered saline (PBS). In vitro MR evaluation indicates that water proton T1 relaxivity or r1 of dND-PG-Gd(III) in aqueous solutions is larger than that of Magnevist(r) and the difference in the relaxivity becomes larger under weaker magnetic fields. The good dispersibility together with relatively high T1 relaxivity makes dND-PG-Gd(III) a promising contrast agent for in vivo MR imaging. PMID- 26353616 TI - Detection of Human Ig G Using Photoluminescent Porous Silicon Interferometer. AB - Photoluminescent porous silicon (PSi) interferometers having dual optical properties, both Fabry-Perot fringe and photolumincence (PL), have been developed and used as biosensors for detection of Human Immunoglobin G (Ig G). PSi samples were prepared by electrochemical etching of p-type silicon under white light exposure. The surface of PSi was characterized using a cold field emission scanning electron microscope. The sensor system studied consisted of a single layer of porous silicon modified with Protein A. The system was probed with various fragments of aqueous human immunoglobin G (Ig G) analyte. Both reflectivity and PL were simultaneously measured under the exposure of human Ig G. An increase of optical thickness and decrease of PL were obtained under the exposure of human Ig G. Detection limit of 500 fM was observed for the human Ig G. PMID- 26353617 TI - Glycyrrhizin Conjugated Dendrimer and Multi-Walled Carbon Nanotubes for Liver Specific Delivery of Doxorubicin. AB - The purpose of the present investigation was to investigate the drug targeting potential of glycyrrhizin (GL) conjugated dendrimers (GL-PPI) and multi walled carbon nanotubes (GL-MWCNTs) towards liver targeting of a model anti-cancer agent, doxorubicin (DOX). The synthesis was confirmed by FTIR, 1H-NMR and morphology analysis. Higher DOX loading was observed in case of GL-PPI-DOX and GL MWCNT-DOX (43.02 +/- 0.64% and 87.26 0.57%, respectively) than parent nanocarriers. GL attachment considerably reduced the haemolytic toxicity of DOX by 12.38 +/- 1.05 and 7.30 +/- 0.63% by GL-PPI-DOX and GL-MWCNT-DOX, respectively. MTT cytotoxicity studies, flow cytometry and cell morphology assessment was done in HepG2 cell. The IC50 of DOX was reduced from 4.19+/-0.05 uM to 2.0+/-0.01 and 2.7+/-0.03 uM, respectively by GL-PPI-DOX and GL-MWCNT-DOX, respectively. Flow cytometry and phase contrast microscopy confirmed GL conjugated formulations to be significantly dragging higher cancer cell number of cells in early apoptosis as well as in early apoptotic phase. PMID- 26353618 TI - Bacopa monniera Stabilized Silver Nanoparticles Attenuates Oxidative Stress Induced by Aluminum in Albino Mice. AB - In the recent years usage of nanomedicine plays a promising strategy in the improvement of medical treatment. The ecofriendly synthesized silver nanoparticles has introduced a new opportunity to increase the efficacy of drug by reducing its side effects. In the present study, we investigated the antioxidant property of Bacopa monniera stabilized silver nanoparticles against aluminum induced toxicity in albino mice. Forty male albino mice were randomly divided into five groups. First group was treated as control, second group received aluminum acetate (5 mg/kg b . w), third group received Bacopa monniera extract (5 mg/kg b . w), fourth group received BmSNPs (5 mg/kg b . w), fifth group received aluminum acetate plus BmSNPs. Exposure to aluminum acetate significantly increased lipid peroxidation levels with a significant decrease in the antioxidant enzymes such as superoxide dismutase, catalase and glutathione peroxidase activities in the brain, liver and kidney of mice. Degenerative changes were also observed in brain, liver and kidney of aluminum treated mice. No significant changes in the oxidative stress were observed in the Bacopa monniera and BmSNPs alone treated mice. Whereas, co-administration of BmSNPs to Al treated mice showed a significant decrease in lipid peroxidation levels with a significant increase of SOD, CAT and GPx indicating the antioxidant potential of nanoparticles and in counteracting Al induced oxidative stress and histological response in male albino mice. These findings clearly implicate that BmSNPs are able to eradicate the oxidative stress and prevent the tissue damage in aluminum exposed mice. PMID- 26353619 TI - Evaluation of beta-Amyloid Peptides Fibrillation Induced by Nanomaterials Based on Molecular Dynamics and Surface Plasmon Resonance. AB - This report investigated the effect of carbon nanomaterials, single-wall carbon nanotube (SWCNT) and graphene oxide, on fibrillation of beta-amyloid 40 (Abeta40) based on surface plasmon resonance (SPR) and molecular dynamics (MD). MD simulations are carried out in order to reveal the molecular mechanisms of the interaction between nanomaterials and Abeta40. The strong interaction between Abeta40 and nanomaterials is related to Van der Waals forces and the Coulomb force, inducing delicate manipulation of the main bonding energy for fibrillation of Abeta40. The interaction energy between the Abeta peptide and graphene is higher than that of SWCNT. Experimental results show both carbon nanomaterials enhance the appearance of a critical nucleus for nucleation of peptide fibrils. Graphene is more beneficial to assist the nucleation process than SWCNT. Combination of SPR and molecular dynamics could be a high-throughput method to screen protein fibrillation. PMID- 26353620 TI - Highly Sensitive Electrical Detection of HIV-1 Virus Based on Scanning Tunneling Microscopy. AB - A highly sensitive immunosensor based on scanning tunneling microscopy (STM) was developed for the first time to detect living material such as HIV-1 virus by gold (Au) nanoparticle and fragmented antibody complex. Fragmented antibodies were pre-immobilized on the Au surface, then HIV-1 virus like particles (HIV-1 VLPs) and Au-nanoparticle and fragmented antibody complexes were applied to develop sandwich assay. The developed surface morphology and the current profile of fabricated immunosensing element were characterized by Raman spectroscopy and investigated with STM. The power spectrum derived from the current profile was found to be related with concentrations of HIV-1 VLPs. Using the electrical detection method based on current mapping profile of STM, living material such as virus, HIV-1 VLPs, was able to be detected successfully. The proposed technique can be a promising method to construct the highly sensitive and efficient sensor for detecting viruses and other living materials. PMID- 26353621 TI - Fluorescent Quantification of DNA Based on Core-Shell Fe3O4@SiO2@Au Nanocomposites and Multiplex Ligation-Dependent Probe Amplification. AB - In this research, a novel method for relative fluorescent quantification of DNA based on Fe3O4@SiO2@Au gold-coated magnetic nanocomposites (GMNPs) and multiplex ligation- dependent probe amplification (MLPA) has been developed. With the help of self-assembly, seed-mediated growth and chemical reduction method, core-shell Fe3O4@SiO2@Au GMNPs were synthesized. Through modified streptavidin on the GMNPs surface, we obtained a bead chip which can capture the biotinylated probes. Then we designed MLPA probes which were tagged with biotin or Cy3 and target DNA on the basis of human APP gene sequence. The products from the thermostable DNA ligase induced ligation reactions and PCR amplifications were incubated with SA GMNPs. After washing, magnetic separation, spotting, the fluorescent scanning results showed our method can be used for the relative quantitative analysis of the target DNA in the concentration range of 03004~0.5 uM. PMID- 26353622 TI - Self-Organized Nanoparticles of Caffeic Acid Conjugated Polysaccharide and Its Anticancer Activity. AB - Caffeic acid-conjugated chitosan (ChitoCFA) and carboxymethyl dextran-b poly(ethylene gycol) (CMD-PEG) copolymer were synthesized to fabricate self organized nanoparticles. Nanoparticles were formed through ion-complex formation between ChitoCFA and CMD-PEG. Nanoparticles have small sizes ranged about 80 nm~300 nm with spherical shapes. Doxorubicin (DOX) was incorporated into the nanoparticles of ChitoCFA/CMD complexes. Particle sizes were increased according to the contents of drug. At drug release experiment, DOX was continuously released over 96 h. Anticancer acticity of nanoparticles were assessed with DOX resistant CT26 cells. CT26 cells treated with DOX-incorporated nanoparticles revealed strong fluorescence intensity while free DOX revealed weak fluorescence intensity, indicating that DOX-loaded nanoparticles of ChitoCFA/CMD are promising vehicle for anticancer drug targeting. PMID- 26353623 TI - Toxicological Characteristics of Titanium Dioxide Nanoparticle in Rats. AB - In an effort to examine liver, heart and kidney injury, immune response, and other physiological effect in rats caused by intratracheal instillation of nano titanium dioxide (TiO2) for 28 days, we assessed T lymphocytes counts, hematological indices, biochemical parameters, cytokines assay and histopathological changes in nano TiO2 treated rats. Indeed, rats treated with nano TiO2 displayed a reduction in body weight and coefficients of the hearts. Edema and loose cytoplasm on liver cells were found in nano groups. The results showed that a statistically significant increased in the BUN, HTC and AST levels than those in control group. Our data suggested that the immunologically competent cells of CD3+, CD4+, and CD8+ caused by nano TiO2 32 mg/kg group were significantly lower than control group. The ratio of CD4+ to CD8+ from the nano 32 mg/kg group was significantly increased and showed a disturbance of cellular immune function. But ELISA analysis showed that no significant changes in IFN gamma and IL-4 were observed throughout the experimental period in this study. PMID- 26353624 TI - High-Content Screening for Assessing Nanomaterial Toxicity. AB - With rapid development of novel nanomaterials (NMs), the state of the art technologies with high efficiency and high-throughput characteristics had been applied for nanosafety evaluation. High-content screening (HCS), a cell-based multi-parametric image analysis technique, was adopted in the evaluation of eight different NMs in this study. A set of different endpoints including reactive oxygen species (ROS) production, Ca2+ transient, mitochondrial membrane potential (MMP) and cellular pH levels were checked in human bronchial epithelial (16HBE) cells after incubating with NMs for 24 hours. All NMs induced significant increase of intracellular ROS levels in 16HBE cells, although the decrease of cell viability was only found in Ag and ZnO NMs-treated cells. MMP level had a dose-response decrease in Ag, ZnO and CeO2 NMs-treated cells, while showed a significant increase in TiO2 NMs-treated cells. All tested NMs showed significant up-regulation of cellular lysosomal pH levels. However, none of NMs caused significant changes in cellular Ca2+ level at 24-hour time point. HCS allows for efficient and reliable screening of multiple responses of cells simultaneously within one screen test, which can avoid the problematic interpretation of investigations when carried on a single toxicological endpoint. Therefore, the present data provide insight and inspiration that HCS is an effective and powerful method for image-based assessments with a broad set of biological endpoints in toxicity evaluation of nanomaterials. PMID- 26353625 TI - Potentiometric Urea Biosensor Based on Carbon Nanotubes and Polyion Complex Film. AB - Enzymatic electrode for a potentiometric urea sensor was prepared by sequential coating of carbon nanotube (CNT), urease (Urs) and polyion complex (mixture of poly-L-lysine hydrobromide and poly (sodium 4-styrenesulfonate), PIC) on an ITO glass. The prepared electrode (ITO/CNT/Urs/PIC) was characterized by potentiometric measurements at different urea concentrations in Tris-HCI buffer (pH 7.0). The potentiometric response of the electrode was linear in the range of 1 x 10(-5) to 3 x 10(-3) M with a correlation coefficient of 0.999 and a sensitivity of 59.1 mV/decade. It was found that the addition of CNT caused considerable improvement of the sensitivity of the electrode to urea. The response time was approximately 60-90 s. A half of the initial sensitivity was retained for 15-17 d at room temperature. PMID- 26353626 TI - Nitrogen-Doped Graphene for Ionic Liquid Based Supercapacitors. AB - Graphene is a promising electrode material for supercapacitor applications due to its unique properties. Interaction of electrolyte ions with graphene lattice sites is a crucial factor in ionic liquid electrolyte based supercapacitors. In an effort to increase the interaction of high viscous electrolyte with electrode material, here, we here report the results of a systematic study carried out on a supercapacitor with nitrogen doped graphene as electrode material and [BMIM][TFSI] as electrolyte. In this study, nitrogen doped hydrogen exfoliated graphene (N-HEG) is prepared by radio frequency (R.F) magnetron sputtering and employed as electrode material for [BMIM][TFSI] electrolyte based high performance supercapacitor. N-HEG shows a high specific capacitance of 170.1 F/g compared to that of electrolyte modified graphene (124.5 F/g), at a specific current of 2 A/g. The improved performance of N-HEG based supercapacitor is attributed to the presence of nitrogen atoms in the graphene lattice which in turn increases the lattice-ion interaction and the electrical conductivity. In addition, the presence of wrinkles on the graphene surface provides a shortest directional path to access pores and surface. The device shows high charge storage capacity (72.37 Wh/kg) along with wide operating voltage (3.5 V) and high cyclic stability. PMID- 26353627 TI - Room Temperature Ion-Beam-Induced Recrystallization and Large Scale Nanopatterning. AB - We have studied ion-induced effects in the near-surface region of two eutectic systems. Gold and Silver nanodots on Silicon (100) substrate were prepared by thermal evaporation under high vacuum condition at room temperature (RT) and irradiated with 1.5 MeV Au2+ ions at flux ~1.25 x 10(11) ions cm-2 s-1 also at RT. These samples were characterized using cross-sectional transmission electron microscopy (XTEM) and associated techniques. We have observed that gold act as catalysis in the recrystallization process of ion-beam-induced amorphous Si at room temperature and also large mass transport up to a distance of about 60 nm into the substrate. Mass transport is much beyond the size (~ 6-20 nm) of these Au nanodots. Ag nanoparticles with diameter 15-45 nm are half-way embedded into the Si substrate and does not stimulate in recrystallization. In case of Au nanoparticles upon ion irradiation, mixed phase formed only when the local composition and transient temperature during irradiation is sufficient to cause mixing in accordance with the Au-Si stable phase diagram. Spectroscopic imaging in the scanning TEM using spatially resolved electron energy loss spectroscopy provides one of the few ways to measure the real-space nanoscale mixing. PMID- 26353628 TI - Selective Two-Photon-Absorption-Induced Reactions of Anthracene-2-Carboxylic Acid on Tunable Plasmonic Substrate with Incoherent Light Source. AB - In this research, we report the development, characterization and application of various plasmonic substrates (with localized surface plasmon resonance wavelength tunable by gold nanoparticle size) for two-photon absorption (TPA)-induced photodimerization of an anthracene derivative, anthracene carboxylic acid, in both surface and solution phase under incoherent visible light irradiation. Despite the efficient photoreaction property of anthracene derivatives and the huge number of publications about them, there has never been a report of a multiphoton photoreaction involving an anthracene derivative with the exception of a reverse photoconversion of anthracene photodimer to monomer with three photon absorption. We examined the progress of the TPA-induced photoreaction by means of surface-enhanced Raman scattering, taking advantage of the ability of our plasmonic substrate to enhance and localize both incident light for photoreaction and Raman scattering signal for analysis of photoreaction products. The TPA-induced photoreaction in the case of anthracene carboxylic acid coated 2D array of gold nanoparticles gave different results according to the properties of the plasmonic substrate, such as the size of the gold nanoparticle and also its resultant optical properties. In particular, a stringent requirement to achieve TPA-induced photodimerization was found to be the matching between irradiation wavelength, localized surface plasmon resonance of the 2D array, and twice the wavelength of the molecular excitation of the target material (in this case, anthracene carboxylic acid). These results will be useful for the future development of efficient plasmonic substrates for TPA-induced photoreactions with various materials. PMID- 26353629 TI - CoS-Graphene Composite Counter Electrode for High Performance Dye-Sensitized Solar Cell. AB - CoS-graphene composite counter electrode for dye-sensitized solar cell (DSSC) was prepared by coating hydrothermal synthesized CoS with graphene onto the FTO conductive glass. SEM shows that CoS particles are uniformly dispersed in the graphene. The result confirms that the prepared composite counter electrode is of highly electrocatalytic activity towards iodine reduction, which is even better than Pt electrode. And cyclic voltammetry measurement also shows that the composite counter electrode has good stability after 100 scan cycles. DSSC with CoS-graphene as composite counter electrode achieves a maximum power conversion efficiency of 6.31%, which is better than Pt electrode. PMID- 26353630 TI - A Novel Graphene Oxide-Based Protein Interaction Measurement Using Atomic Force Microscopy. AB - Graphene oxide (GO) is a promising material for biological applications because of its excellent physical/chemical properties such as aqueous processability, amphiphilicity, and surface functionalizability. Here we introduce a new biological application of GO, a novel GO-based technique for probing protein interactions using atomic force microscopy (AFM). GO sheets were intercalated between the protein-modified AFM probe and the polymer substrate in order to reduce the non-specific adhesion force observed during single-molecule force spectroscopy (SMFS). In this study, we used SMFS to probe the interaction of the actin filament and actin-related protein 2/3 complex (Arp2/3), an actin-binding protein. Our results confirm that the GO sheet reduces nonspecific adhesion of the probe to the substrate. Using the GO-based technique, we succeeded in estimating the dissociation constant of the actin filament-binding protein interaction. PMID- 26353631 TI - Direct Assembly of Graphene Oxide on Flexible Substrates for Highly Transparent Electrodes via the Langmuir-Blodgett Technique. AB - The surface activity of graphene oxide (GO) offers an ideal building block upon which to construct two-dimensional (2D) nanostructures via side-by-side assembly strategies. In this work, we demonstrate the Langmuir-Blodgett assembly of GO into a 2D film with a carbon monolayer thickness on a PET substrate over a large area. After the reduction of the GO films at a low temperature, transparent flexible conducting films were realized. Our straightforward route for preparing graphene-based transparent films provides a controlled strategy to coat graphene monolayers on flexible substrates. PMID- 26353632 TI - Current Scaling and Dirac Fermion Heating in Multi-Layer Graphene. AB - We have performed transport measurements on a multi-layer graphene device fabricated by conventional mechanical exfoliation. By using the zero-field resistance of our graphene device as a self-thermometer, we are able to determine the effective Dirac fermion temperature TDF at various driving currents I while keeping the lattice constant fixed. Interesting, it is found that TDF is proportional to Ia where a ~ 1. According to theoretical and experimental studies, the exponent a is given by 2/(2+p) where the charge-phonon scattering rate 1/tauph is proportional to TP. Therefore our results yield p ~ 0, suggesting that there is little Dirac fermion-phonon scattering, a great advantage for applications in nanoelectronics. PMID- 26353633 TI - Oscillatory Behavior of Graphene Nanoflake on Graphene Nanoribbon. AB - We investigated the oscillatory behaviors of graphene-nanoflake on graphene nanoribbon via classical molecular dynamics simulations. Since the potential well had constant depth along the length axis of the graphene-nanoribbon, such as a ditch, and the retraction van der Waals forces at both edges were exerted, the movable graphene-nanoflake could be shuttled between both sides of the graphene nanoribbon, along the direction of the ditch in the potential well. When the graphene-nanoflake was extruded from the graphene-nanoribbon, the telescoping region of the graphene-nanoflake was bent by the attractive force between the graphene-nanoribbon and the graphene-nanoflake, and this bending caused the flapping or wagging motions of the graphene-nanoflake, which dissipated the kinetic energy of the graphene-nanoflake. So this phenomenon greatly affected the oscillatory behaviors of the graphene-nanoflake. The resonance frequencies were dependent on the initial velocity of the graphene-nanoflake. The graphene nanoflake on the graphene-nanoribbon is applicable to ultra-fast response oscillators, data storage media, switches, sensors, and quantum computing. PMID- 26353634 TI - Ripple-Free Graphene Sheets on Alkanethiol Self-Assembled Monolayers Provided from Unzipped Multi-Walled Carbon Nanotubes. AB - Octanethiol (C8S, CH3(CH2)7SH) self-assembled monolayers/Au(111) were utilized as an inert surface to provide ripple-free graphene oxide layers provided from chemically unzipped multi-walled carbon nanotubes (MWCNTs). The resulting graphene oxide monolayers were characterized with atomic resolution by UHV-STM. The honeycomb structure for the graphene monolayer and "three-for-six" triangular pattern for the multi-layer graphene sheets on C8S SAMs were clearly observed without ripples by the high-resolution UHV-STM. These results provide new insight into the preparation of ripple-free graphene monolayers. PMID- 26353635 TI - Formation of Silica/Graphene Oxide Hybrid Nano Films by Layer-by-Layer Self Assembly and Biomimetic Silicification. AB - Silica/graphene oxide hybrid thin films were formed by layer-by-layer self assembly and biomimetic silicification, and the thickness and structure of hybrid thin films were finely controlled at the nanometer scale, by tuning number of the layer-by-layer process. The physical properties of thin films were characterized by infrared spectroscopy, atomic force microscopy, and scanning electron microscopy. In addition, silica/graphene oxide hybrid thin films were successfully utilized for cell culture platforms. PMID- 26353636 TI - Enhanced Stability and Reusability of Alcohol Dehydrogenase Covalently Immobilized on Magnetic Graphene Oxide Nanocomposites. AB - Graphene oxide (GO) has a unique planar structure and contains many functional groups. As a functional material, it can be functionalized with biomolecules and nanomaterials for various applications. In this study, Magnetic GO (MGO) nanocomposites were synthesized according to covalent binding of amino Fe3O4 nanoparticles onto the GO surface and the as-made nanocomposites were successfully applied as supports for the immobilization of alcohol dehydrogenase (ADH). Compared with free ADH and Fe3O4 nanoparticles immobilized ADH (MNP-ADH), the MGO immobilized ADH (MGO-ADH) exhibited a wider pH stability range and a better thermal stability. Furthermore, the MGO-ADH exhibited better storage stability and reusability than MNP-ADH after recovered by magnetic separations. The MGO-ADH maintained 35.1% activity after 20 days storage and lost about 20.4% activity after ten times usage. The Michaelis constant (Km) of MGO-ADH was close to that of free ADH. The results showed the MGO nanocomposites were appropriate for the immobilization of enzyme. As a novel support, MGO nanocomposites effectively increased the stability of enzyme, allowed the reuse or continuous use of enzymes and therefore improved the potential use in practical. PMID- 26353637 TI - Large-Area, Highly Ordered Array of Graphitic Carbon Materials Using Surface Active Chitosan Prepatterns. AB - We demonstrate that chitosan prepatterns can generate not only highly periodic DNA pattern but also various types of graphitic carbon materials such as single walled carbon nanotubes (SWNTs), graphene oxide (GO) and reduced graphene oxide (RGO). Scanning electron microscopy (SEM), fluorescence imaging and Raman spectroscopic results revealed that the graphitic carbon materials were selectively deposited on the surface of the periodic chitosan patterns by the electrostatic interaction between protonated amine groups of chitosan and the negative charged carbon materials. One proof-of-concept application of the system to the fabrication of electrical devices based on the micropatterns of SWNTs and RGO was also demonstrated. The strategy to use highly surface active chitosan pattern that can easily fabricate highly periodic pattern via a variety of lithographic tools may pave the way for the production of periodic arrays of graphitic carbon materials for large area device integration. PMID- 26353638 TI - The Surface Modification and Antimicrobial Activity of Basic Magnesium Hypochlorite Nanoparticles. AB - The basic magnesium hypochlorite (BMH) nanoparticles were prepared by two micro emulsion techniques and modified with sodium stearate. The influences of the main technical parameters such as the addition amount of sodium stearate, reaction temperature and reaction time on the Lipophilic degree (LD) of the modified BMH nanoparticles were investigated. The characteristics of the BMH nanoparticles were analysed by means of Malvern Instruments, transmission electron microscopy (TEM), water contact angle measurements, Fourier transform infrared spectroscopy (FTIR) and thermogravimetry analysis (TGA). The antimicrobial activity of the modified BMH nanoparticles was investigated with the antibacterial circle test. The results showed that the average size of the BMH nanoparticles was 305 nm. The BMH nanoparticles had been successfully modified by sodium stearate and the LD of.the modified BMH nanoparticles was 8.4% when the addition amount of sodium stearate was 0.15 g, the reaction temperature was 10 degrees C and the reaction time was 5 h. The dispersibility and hydrophobicity of the modified BMH nanoparticles were improved and the contact angle was up to 103 degrees , the modified BMH nanoparticles still had excellent antimicrobial activity after modification. PMID- 26353639 TI - Insights Into Oxygen Adsorption on Ag-Cu Nanocluster as an Oxidation Catalyst by Ab Initio Atomistic Thermodynamics. AB - To understand the catalytic activity of Ag-Cu cluster as catalyst of ethylene oxidation, bare Ag and Cu and Ag core/Cu12 shell and Cu core/Ag12 shell are built and optimized by density functional theory calculations incorporating the effect of the atmospheric environment. Consequently different oxygen adsorption sites on the cluster are considered: top site of the shell atoms, bridge site of the shell atoms and hollow site of the shell atoms. For each adsorption site, a few coverages are considered, both oxygen-rich condition and oxygen-poor condition. The phase diagrams of oxygen and 13-atom Ag-Cu clusters are finally determined. The pressure-temperature phase diagrams are determined for the oxygen and 13-atom Ag-Cu clusters, which reveal important insights into this system and its catalytic properties. The phase diagrams of oxygen and 13-atom Ag-Cu clusters are finally determined. The results predict the most stable phase: structure and adsorption of oxygen at certain temperature and certain pressure. Under oxygen poor condition, the cluster structures are most likely to be changed. This information must be helpful to understand the catalytic process of Ag-Cu cluster as catalyst of ethylene oxidation. PMID- 26353640 TI - Gas Sensing Properties of ZnO-SnO2 Nanostructures. AB - One-dimensional (1D) semiconductor metal oxide nanostructures have attracted increasing attention in electrochemistry, optics, magnetic, and gas sensing fields for the good properties. N-type low dimensional semiconducting oxides such as SnO2 and ZnO have been known for the detection of inflammable or toxic gases. In this paper, we fabricated the ZnO-SnO2 and SnO2 nanoparticles by hydrothermal synthesis. Microstructure characterization was performed using X-ray diffraction (XRD) and surface morphologies for both the pristine and doped samples were observed using field emission scanning electron microscope (FESEM), transmission electron microscopy (TEM) and high resolution transmission electron microscopy (HRTEM). Then we made thin film gas sensor to study the gas sensing properties of ZnO-SnO2 and SnO2 gas sensor to H2 and CO. A systematic comparison study reveals an enhanced gas sensing performance for the sensor made of SnO2 and ZnO toward H2 and CO over that of the commonly applied undecorated SnO2 nanoparticles. The improved gas sensing properties are attributed to the size of grains and pronounced electron transfer between the compound nanostructures and the absorbed oxygen species as well as to the heterojunctions of the ZnO nanoparticles to the SnO2 nanoparticles, which provide additional reaction rooms. The results represent an advance of compound nanostructures in further enhancing the functionality of gas sensors, and this facile method could be applicable to many sensing materials, offering a new avenue and direction to detect gases of interest based on composite tin oxide nanoparticles. PMID- 26353641 TI - Two-Dimensional Mesoporous Carbon Electrode for High Energy Density Electrochemical Supercapacitors. AB - Mesoporous carbon (MPC) with highly textured, reproducible and uniform structure is prepared by silica-sol template assisted method, as new carbonaceous supercapacitor materials with high energy density. High resolution transmission electron microscopy studies revealed that the MPC consisted of textured structure of carbon on the sheets like domains and exhibited a specific surface area of 1412 m2 g-1. The symmetric supercapacitor of MPC exhibits an excellent cyclability over 5000 cycles and high energy density of 84.6 Wh kg-1, with a cell potential of 1.6 V and a large specific capacitance of 238 F g-1 in neutral electrolyte. The enhanced performance of the carbon material as a supercapacitor electrode is due to the synergetic effect possibly contributed from the fast ion transportation during fast charge/discharge and better utilization of carbon. PMID- 26353642 TI - Simultaneous Enhancement of Intracellular Optical Imaging and Photothermal Therapeutic Response by Octaarginine-Modified Fluorescent Dye Doped Pd@Ag@SiO2(RITC) Multifunctional Nanoparticles. AB - In the work, a novel multifunctional silica-based nanoplatform (Pd@Ag@SiO2(RITC) R8) for bioimaging and photothermal therapy (PTT) of cancer cells has been developed. The Pd@Ag nanosheets encapsulated inside silica can act as effective near-infrared (NIR) absorbers for cancer photothermal therapy. Fluorescent dye, rhodamine B isothiocyanate (RITC), was covalently doped into the silica network to provide the capacity for optical imaging. After amine modification, the Pd@Ag@SiO2(RITC)-NH2 can be further conjugated with octaarginine (R8, a cell penetrating peptide) for enhancing the uptake of nanoparticles by cells. Confocal fluorescent images and flow cytometry analysis revealed that R8-conjugated nanoparticles (Pd@Ag@SiO2(RITC)-R8) were taken up by cells more efficiently. Correspondingly, the optical imaging and photothermal therapeutic efficiency of Pd@Ag@SiO2(RITC)-R8 upon cancer cells were also raised due to their higher cellular uptake when compared with that of Pd@Ag@SiO2(RITC)-NH2. Our results indicate that these multifunctional Pd@Ag@SiO2(RITC)-R8 may have great potential for applications in imaging-guided cancer photothermal therapy. PMID- 26353643 TI - All-Electron Scalar Relativistic Calculations on the Adsorption of Small Gold Clusters Toward Methanol Molecule. AB - Under the framework of DFT, an all-electron scalar relativistic calculation on the adsorption of Aun (n = 1-13) clusters toward methanol molecule has been performed with the generalized gradient approximation at PW91 level. Our calculation results reveal that the small gold cluster would like to bond with oxygen of methanol molecule at the edge of gold cluster plane. After adsorption, the chemical activities of hydroxyl group and methyl group are enhanced to some extent. The even-numbered AunCH3OH cluster with closed-shell electronic configuration is relatively more stable than the neighboring odd-numbered AunCH3OH cluster with open-shell electronic configuration. All the AunCH3OH clusters prefer low spin multiplicity (M = 1 for even-numbered AuNCH3OH clusters, M = 2 for odd-numbered AunCH3OH clusters) and the magnetic moments are mainly contributed by gold atoms. The odd-even alterations of magnetic moments and electronic configurations can be observed clearly and may be simply understood in terms of the electron pairing effect. PMID- 26353644 TI - Biogenic Preparation of Gold Nanostructures Reduced from Piper longum Leaf Broth and Their Electrochemical Studies. AB - Exploitation of green chemical procedures for the synthesis of metal nanoparticles by biological process has received great attention in the field of nanotechnology. To demonstrate a biogenic method that involves the reduction of aqueous gold ions by the extract of Piper longum leaves leading to the formation of different morphological gold nanoparticles (AuNPs). The formation of gold nano structures has been characterized by UV-Vis absorption spectroscopy. The X-ray diffraction (XRD) and selected area electron diffraction (SAED) patterns indicates the AuNPs are highly crystalline nature with the face-centered cubic (111), (200), (220) and (311) facets, respectively. The AuNPs have different sizes and morphologies that are identified by TEM studies. The involvement of water soluble bio-molecules such as carboxylic acids, flavonoids, proteins and terpenoids were identified by Fourier transform infrared (FT-IR) and Raman spectrum. The responsible mechanism of improving acidic nature and the process of encapsulation of gold nanoparticles by Piper longum extract was discussed. Additionally, we have demonstrated the modified carbon paste electrode using gold nanoparticles by means of cyclic voltammetry in a solution of 1 M KCI and 1 mM [Fe(CN)6]3-/4-. The analysis of cyclic voltammetry shows electronic transmission rate between modified Au-CPE and Bare-CPE electrode increased. PMID- 26353645 TI - Synthesis of Carbon Nanohelices Using Sn Based Bi-Metal Oxide Catalysts. AB - In this article, we report the synthesis of carbon nanohelices (CNH) by catalytic chemical vapor deposition (CCVD) technique using novel inorganic bi-metal oxide catalysts. The catalysts chosen have the general form X-Sn-O, where X refers to element having high carbon solubility such as Fe and Ni. These catalysts are synthesized by simple sol-gel technique. The CNH are grown by CCVD method at a temperature of 700 degrees C by taking acetylene as the carbon source. A reasonably good yield (40-60%) of CNH is obtained with each catalyst. The catalysts and CNH are characterized using different experimental techniques like X-ray diffraction, Raman spectroscopy, electron microscopy and thermogravimetric analysis. These characterizations suggest that morphology as well as the constituents of the metal oxide catalysts have significant influence on the coil and spiral growth of CNH. Finally, electrochemical study of the CNH shows good catalytic activity in 1 M H2SO4 aqueous solution compared to bare electrode and is therefore ideal for many applications. PMID- 26353646 TI - Direct Tailoring the Si Substrate for Antireflection via Random Nanohole Nanoimprint. AB - In this paper, a 2 inch random nanohole Si template with hole diameter of 36-97 nm is employed for direct tailoring the Si substrate for antireflection. The random nanohole Si template is fabricated from the natural self-organization process and can be used repeatedly in nanoimprint lithography (NIL). The surface roughness induced from the nanohole structured surface enhanced the antiadhesion property (contact angle of 128 degrees ) of the Si template for high accuracy soft mold replication. The random nanohole structured polymer/Si substrate has a surface fluctuation of ~3 nm, which ensures a uniform and effective pattern transfer from resist to substrate. The reflectivity of the random nanohole structured Si substrate decreases from around 34% to less than 5% with the hole aspect ratio within 3.0 in the wavelength region of 400-800 nm. This method is simple, cheap, repeatable in large area and compatible with the high volume production lines. PMID- 26353647 TI - Efficient Catalytic Activity BiFeO3 Nanoparticles Prepared by Novel Microwave Assisted Synthesis. AB - A novel microwave-assisted sol-gel method was applied to the synthesis of the single-phase perovskite bismuth ferrite nanoparticles (BFO NPs) with the mean diameter ca. 73.7 nm. The morphology was characterized by scanning electron microscope (SEM). The X-ray diffraction (XRD) revealed the rhombohedral phase with R3c space group. The weak ferromagnetic behavior at room temperature was affirmed by the vibrating sample magnetometer (VSM). According to the UV-vis diffuse reflectance spectrum (UV-DSR), the band gap energy of BFO NPs was determined to be 2.18 eV. The electrochemical activity was evaluated by BFO NPs chitosan-glassy carbon electrode (BFO-CS-GCE) sensor for detection of p nitrophenol contaminants. The material showed an efficient oxidation catalytic activity by degrading methylene blue (MB). It was found that the degradation efficiency of 10 mg L-1 MB at pH 6.0 was above 90.9% after ultrasound- and microwave-combined-assisted (US-MW) irradiation for 15 min with BFO NPs as catalyst and H202 as oxidant. A possible reaction mechanism of degradation of MB was also proposed. PMID- 26353648 TI - Tunable Device Parameters of Polymer/CulnS2 Solar Cells Depending on CulnS2 Quantum Dot Size. AB - This paper reports tunable device parameters of polymer/CuInS2 solar cells depending on CulnS2 quantum dot size, for the first time. The CuInS2 quantum dots (CuInS2-QDs) of tunable sizes displayed size-dependent band gaps, following by the size-dependent morphologies and optical properties in MEH-PPV-CuInS2 composites. Polymer/CulnS2 solar cells with poly(2-methoxy-5-(2-ethylhexyloxy) 1,4-phenylene vinylene) (MEH-PPV) as polymer exhibited tunable device parameters depending on CuInS2-QDs size, resulting in a maximum power conversion efficiency of ca. 0.12% under the monochromic illumination at 470 nm in the device with the small-sized CuInS2-QDs. The origins for size-dependent performance in the solar cells are elucidated, which suggests that the higher short circuit current (Jsc) in the MEH-PPV/CuInS2 device with the small-sized QDs may due to the increased MEH-PPV/CuInS2 interface areas, while the higher open circuit voltage (Voc) may result from the higher energy difference between the conduction band position (Ec) of CuInS2-QDs and the highest occupied molecular orbital (HOMO) of the polymer. In particular, it is found that the device Voc is linearly dependent on the energy difference between Ec of CuInS2-QDs and HOMO of the polymer. PMID- 26353649 TI - Mechanistic Study of Silver Nanoparticle's Synthesis by Dragon's Blood Resin Ethanol Extract and Antiradiation Activity. AB - Biological synthesis of nanoparticles is best way to avoid exposure of hazardous materials as compared to chemical manufacturing process which is a severe threat not only to biodiversity but also to environment. In present study, we reported a novel method of finding antiradiation compounds by bioreducing mechanism of silver nanoparticles formation using 50% ethanol extract of Dragons blood, a famous Chinese herbal plant. Color change during silver nanoparticles synthesis was observed and it was confirmed by ultra violet (UV) visible spectroscopy at wave length at 430 nm after 30 min of reaction at 60 degrees C. Well dispersed round shaped silver nanoparticles with approximate size (4 nm to 50 nm) were measured by TEM and particle size analyser. Capping of biomolecules on Ag nanoparticles was characterized by FTIR spectra. HPLC analysis was carried out to find active compounds in the extract. Furthermore, antiradiation activity of this extract was tested by MTT assay in vitro after incubating the SH-SY5Y cells for 24 h at 37 degrees C. The results indicate that presence of active compounds in plant extract not only involves in bioreduction process but also shows response against radiation. The dual role of plant extract as green synthesis of nanoparticles and exhibit activity against radiation which gives a new way of fishing out active compounds from complex herbal plants. PMID- 26353650 TI - Numerical Investigation on Micro-Cavity Effect of Top-Emitting Organic Light Emitting Diode. AB - In this paper, we report our numerical investigation on the top-emitting OLED (Organic Light Emitting Diodes) with micro-cavity. Our numerical model includes an ensemble of radiating dipole antennas for light emission as well as Poisson Equation for carrier injection and transportation. We formulated a set of differential equations by the Finite Element Method. Our simulation revealed that the recombination rate is affected by the thickness of each layer comprising the OLED structure and the amount of emission is determined by the total thickness of the OLED structure due to micro-cavity effect which is observed in between the total reflection layer and the half reflection layer. Our numerical solver enables us to optimize the OLED structure and thereby improve the external quantum efficiency. PMID- 26353651 TI - Fabrication of Hierarchical ZnO/Si Nanowire Structure for Photoelectrochemical Cells. AB - We demonstrate the fabrication of three dimensional hierarchical ZnO/Si nanowire core-shell structure, which is used as a high surface area photoelectrode in photoelectrochemical cells for solar water splitting. This structure is fabricated via a two-step solution process: fabricating vertical aligned silicon nanowires via metal assisted etching method and then growing ZnO nanowires on the silicon nanowires via hydrothermal method. Transmission electron microscopy, scanning electron microscopy, spectrometer and X-ray diffractmeter are employed to characterize the hierarchical structure. The surface area of the hierarchical structure increases significantly compared to the simplex nanowire structure, which can substantially promote the photoelectrochemical reactions. The core shell characteristic is beneficial to the charge carrier separation and the silicon nanowire backbones can work as the charge transfer channels, which contribute to the efficiency improvement. The experimental results indicate that the photocurrent density and the maximum conversion efficiency of the hierarchical structure photoelectrode have increased obviously, confirming that this hierarchical structure is more suitable for the application of photoelectrode than the ZnO nanowires/planar silicon structure. PMID- 26353652 TI - Electrochemically Active Polyaniline (PANi) Coated Carbon Nanopipes and PANi Nanofibers Containing Composite. AB - A composite constituted by carbon nanopipes (CNPs) and polyaniline nanofibers (PANi NFs) is synthesized using in-situ chemical oxidative polymerization. Owing to its electrochemical activity the composite is found to be suitable as a working electrode material in hybrid type supercapacitors. Microstructural and phase analyses of the composite showed that (i) CNP surfaces are coated with PANi and (ii) PANi coated CNPs are distributed among PANi NFs. The composite shows an excellent electrochemical activity and a high specific capacitance of ~224.39 F/g. The electro-chemical activity of the composite is explicated in correlation with crystallinity, intrinsic oxidation state, and doping degree of PANi in the composite. The electro-chemical activity of the composite is also explicated in correlation with BET surface area and ordered meso-porosity pertaining to the composite. Charge/discharge curves indicate that the specific capacitance of the composite is a result of electric double-layer capacitance offered by CNPs and Faradaic pseudo capacitance offered by PANi NFs. PMID- 26353653 TI - Preparation and Optical Absorption Performance of Si Single Quantum Dots and Si/Ge Double Quantum Dots Doped TiO2 Films. AB - Si single quantum dots (QDs) and Si/Ge double QDs doped TiO2 films were successfully fabricated via layer-by-layer ion beam sputtering assisted by annealing treatment, and their morphology and optical absorption performance were analyzed in this paper. TEM images show that Si QDs and Si/Ge double QDs prepared in the TiO2 matrix are in a uniform size distribution and high density, especially after annealed at 500 degrees C. XPS results indicate that Si in the TiO2 films mainly exists in the form of elemental Si and SiO2, and Ge is in elemental form. From the optical absorption spectra, the optical response of the TiO2 films is shifted from ultraviolet to visible and near infrared region when they are doped by the QDs, and the Si/Ge double QDs co-doped TiO2 films show better optical response compared with the Si QDs doped TiO2 films, suggesting a hybrid enhanced effect of double QDs. PMID- 26353654 TI - Development and Quality Control of Nanohexaconazole as an Effective Fungicide and Its Biosafety Studies on Soil Nitifiers. AB - The study was aimed to develop a nano form of an existing fungicide for improving plant protection and reducing crop losses caused by fungal pathogens. The protocol for the preparation and estimation of nanohexaconazole was developed. Technically pure hexaconazole was converted into its nanoform using polyethyleneglycol-400 (PEG) as the surface stabilizing agent. Nanohexaconazole was characterized using Scanning Electron Microscopy (SEM) and Dynamic Light Scattering (DLS) studies. The average particle size of nanohexaconazole was about 100 nm. An analytical method was also developed for quality control of the nanofungicide by GLC fitted with flame ionization detector. Its limit of detection was 2.5 ppm. Fungicidal potential of nanohexaconazole was better in comparison to that of conventional hexaconazole. Hydrolytic and thermal stability studies confirmed its stability at par with the conventional formulation of fungicide. Impact of nanohexaconazole on soil nitrifiers was tested in vitro and there were no significant adverse effect in their numbers observed as compared to conventional registered formulation, proving the safety of the nanofungicide. PMID- 26353655 TI - Rapid Visual Detection of Aflatoxin B1 by Label-Free Aptasensor Using Unmodified Gold Nanoparticles. AB - The selective detection of ultra trace amounts of aflatoxin B1 (AF1) is extremely important for food safety, since it is the most toxic mycotoxin class that is allowed to be present in edible food and agricultural products with strictly Maximum Residue Limit (MRL). Sensitive detection of AFB1 residues requires time consuming techniques and expensive instruments. An aptasensor for AFB1 detection, using unmodified gold nanoparticles (AuNPs) indicator, was developed in the present study, based on the salt-induced AuNPs aggregation phenomenon. Its linear dynamic range and detection sensitivity were found to be 0.025 ng/mL-100 ng/mL and 0.025 ng/mL of AFB1 respectively, which were lower than the maximum residue limit (MRL) in edible food, as set by China and the European Commission. Our study provides a simple, fast, and visible method for AFB1 analysis, with high sensitivity, which can be applied in future on-site detection for food and agricultural products. PMID- 26353656 TI - Synthesis of Nano-Crystalline Materials in Open-Air Laboratory: A Case Study of Tobacco. AB - The work deals with synthesis of nano-crystalline materials in open-air laboratory and in-depth investigation of the tobacco sample of one branded cigarette and its ash using high-resolution transmission electron microscopy and associated techniques. It exhibits the presence of nanocrystals and nanorods of various oxides in cigarette ash. The structure, shape, size and composition of these nanocrystals and nanorods are explored. The energy dispersive X-ray spectra from different regions of the tobacco sample and its ash using high-angle annular dark field scanning/transmission electron microscopy mode are utilized to obtain elemental composition and their relative abundances. For a detailed distribution of different elements in the nanorods, elemental mapping using energy-filtered transmission electron microscopy is also presented. The results highlight the conversion of amorphous constituents of tobacco to nanomaterials on combustion at low temperatures, thus mixing up in the atmosphere. PMID- 26353657 TI - Computational Nanopatterning in the Plasmonic Metamaterials for Diffraction Limit. AB - For technologies beyond diffraction limit, the plasmonic nanolithography can produce subwavelength structures using the broad beam illumination of the standard photoresist with the visible light. In this study, for the nano-pattern formation, the polarization effects of the transverse magnetic (TM) mode and the transverse electric (TE) mode about diffraction limit and plasmonic phenomena are described on basis of simulation results through the sub-wavelength aperture. TM mode is degraded in diffraction effects but enhanced in plasmonic effects due to the change distribution on the metallic surface and the waveguide resonances in slits. For the confidence of simulation results, those results are compared with experiment results of the pyramidal horn with mirror. For the contact lithography, it is shown that the resolution of plasmonic metamaterial masks is enhanced larger than that of the conventional mask by using a multi-layer method. PMID- 26353658 TI - Electrical and Optical Analysis on Green Organic Light Emitting Device Using Finite Element Method. AB - In this paper, we report our numerical study on the electronic-optical properties of the organic light emitting diodes (OLEDs) devices. In order to calculate the electrical and optical characteristics such as the transport behavior of carriers, recombination kinetics, and emission property, we undertake the finite element method (FEM) in OLEDs. Our model includes Poisson's equation, continuity equation to account for behavior of electrons and holes and the exciton continuity/transfer equation to account for generation and decay of the exciton. We employ the multilayer structure that consists of Poly(3,4)-ethylendioxy thiophene-polystyrenesulfonate ( PEDOT: PSS); Bis[(1-naphthyl)-N-phenyl]benzidine (alpha-NPD); 4,4'-N,N'-dicarbazole-biphenyl (CBP) doped with Ir(ppy)3; a 2-(4 Biphenylyl)-5-(4-tert-butylphenyl-1,3,4-oxadiazole) (Bu-PBD). We demonstrate that the refractive indexes of each material affect the emission property and barrier height of the interface influences the behavior of charges and the generation of exciton. PMID- 26353660 TI - Synthesis of Cubic Alpha-Alumina Using a Blocking Reagent of Tetraethyl Ammonium Hydroxide. AB - This study was an attempt to obtain a stable and reproducible cubic primary alumina by a hydrothermal method using various aluminum precursors, AIP, AlO(OH), and Al(OH)3. Tetraethyl ammonium hydroxide was introduced as a blocking reagent to control the shape of alumina. The synthesized primary alumina powders from Al precursors showed a boehmite structure after hydrothermal treatment at 200 degrees C for 1 h. The primary alumina powders synthesized using the precursors of AIP and AlO(OH) had irregular shapes, however the cubic-shape of approximately 300 nm was observed in the primary alumina powder synthesized using Al(OH)3 precursor. The cubic primary alumina samples were transformed to different solid phases like gamma-, delta-, theta-, and alpha-phases according to the calcined temperatures. The theta-phase alumina formed at 1100 degrees C continually kept the cubic shape, but the shape was collapsed at 1200 degrees C. However the cubic alpha-alumina alpha-alumina was stably remained by thermal treatment at 1100 degrees C under the fierce oxygen atmosphere. PMID- 26353659 TI - Property Control of Layer-by-Layer Assembled Sulfonated Poly(phenylene oxide) Composite Membrane Based on Nafion for Fuel Cell Applications. AB - Multilayered composite proton exchange membranes were prepared by LbL method by alternating deposition of poly(diallyl dimethyl ammonium chloride) (PDDA) and highly sulfonated poly(phenylene oxide) (sPPO) onto the surface of Nafion 212. The sulfonated sPPO solution contained polystyrenesulfonic acid copolymer with azide moiety. Thickness of the LbL composite membrane was controlled by using the anionic solution of sPPO containing 0.5 M NaCl. The membranes were crosslinked by using UV to give the mechanical and chemical durability. The crosslinked composite membrane showed decreased methanol permeability with the increasing number of bilayers, and showed increased overall selectivity compared to Nafion film. PMID- 26353661 TI - Preparation and Luminescent Property of the Self-Assembled Nanoscale Network Systems Combined Tetracyanoplatinate(II) and Copper(II)-Polyaza Complexes. AB - Complexes 1 and 2 were obtained by the reaction of [Cu(L1)](ClO4)2 (1) or [Cu(L2)](ClO4)2 (2) (L1 = 8-acetyl-1,3,6,8,10,13,15 heptaazatricyclo[13.1.1.113,15]octadecane, L2 = 3,7-bis(2-aminoethyl)- 1,3,5,7 tetraazabicyclo[3.3.l]decane) with K2[Pt(CN)4] in water. The X-ray crystal structures show that the geometry around Cu(II) ions of 1 and 2 adopts a square pyramid. Their one-dimensional and two-dimensional structures are constructed by the intermolecular hydrogen bonding between the macrocyclic ligand and anionic complex ions or water molecules and Pt-Pt interaction. They show luminescent property and luminescence quantum yields are 0.341 and 0.187 for 1 and 2 in solid, respectively. PMID- 26353662 TI - Synthesis and Characterization of New Tercopolymer Containing Thienothiophene, Thiophene and Fluorene for Organic Thin-Film Transistors. AB - We have designed and synthesized the novel p-type polymer containing thienothiophene, thiophene and fluorene with OTFT characteristics. The polymer was synthesized by the palladium catalyzed Suzuki coupling reaction with thienothiophene derivatives, thiophene derivatives and fluorene derivatives. The obtained PTT2BTF can dissolve in common organic solvents such as toluene, THF, chloroform, chlorobenzene and dichlorobenzene. PTT2BTF has a number average molecular weight (Mn) of 25,000 with a poly dispersity index (PDI) of 1.66. PTT2BTF showed good thermal stability with high Td of 407 degrees C. The OTFT characteristics of the polymer (PTT2BTF) were fabricated. Organic semiconductor was found to exhibit typical p-channel FET characteristics with a hole mobility of 6.3 x 10(-5) cm2/Vs and a threshold voltage of - 4 V. Keywords: OTFT, Thiophene, Fluorene, Solution Process. PMID- 26353663 TI - A Point-of-Care Prothrombin Time Test on a Microfluidic Disk Analyzer Using Alternate Spinning. AB - In this study, we conducted a fully integrated point-of-care prothrombin time test on a microfluidic disk analyzer. The microfluidic functions integrated on the disk were capable of separating whole blood, decanting plasma, and mixing it with reagents in sequence under alternate spinning. The assay protocol was completed by alternate spinning without using microvalves or surface modification. Clinical sample tests on prothrombin time measurement were conducted by both the microfluidic disk analyzer and the reference instrument used in medical centers. The test results showed a good correlation and agreement between the two instruments. PMID- 26353664 TI - Photocatalytic Performance of a Nd-SiO2-TiO2 Nanocomposite for Degradation of Rhodamine B Dye Wastewater. AB - The photocatalytic performance of a novel Nd-SiO2-TiO2 nanocomposite catalyst prepared by a sol-gel method was examined in the degradation of Rhodamine B (RhB), a notorious organic compound present in dye wastewaters. The prepared samples were characterized by low-temperature N2 adsorption, X-ray diffraction (XRD), transmission electron microscopy (TEM) and UV-vis diffuse reflectance spectroscopy (DRS). Fourier-transform infrared (FT-IR) spectroscopic analysis indicated the enhanced chemical bonding of O--Ti and O--Ti--O with introduction of Nd and SiO2 dopant species into TiO2. The Nd-SiO2-TiO2 nanocomposite was found to exhibit a much higher photo- catalytic activity toward the decomposition of RhB under both UV and visible light irradiation as compared to a commercial TiO2 photocatalyst. The photodegradation efficiency of RhB (5 mg/L) was greater than 93% under visible light irradiation after 90 min. Addition of SiO2 was shown to not only inhibit crystal growth and TiO2 anatase-to-rutile phase transformation, but also enhance the adsorption of organic compounds. Nd doping has been suggested for slowing down the radiative recombination of photo-generated electrons and holes in TiO2, extending the photocatalyst light response to the visible region. The synergetic effects between Nd-SiO2 and TiO2 are described; the prepared Nd-SiO2-TiO2 represents a noteworthy contribution to the study of pollutant degradation in dye wastewaters. PMID- 26353665 TI - Improved Memory Effect of ZnO Nanorods Embedded in an Insulating Polymethylmethacrylate Layer. AB - Fabrication and characterization of memory devices using ZnO nanorod layer grown by chemical-bath method is reported. The fabricated memory device was found exhibit electrical bistability and nonvolatile memory phenomenon. An additional Polymethylmethacrylate (PMMA) polymer layer coated on ITO substrate prior to nanorod deposition has been found improve the LRS/HRS ratio of the device. The current-voltage characteristics of the memory devices are discussed in terms of formation and rupture of conductive filaments. The devices have shown consistent electrical bistable behavior even for 10(5) resistance-switching cycles. This hybrid ITO/PMMA-ZnO NRs/Al device has potential applications in the field of bistable random access memories. PMID- 26353666 TI - Template-Free Synthesis and Enhanced Photocatalytic Performance of Uniform BiOCI Flower-Like Microspheres. AB - Preparation of uniform BiOCI flower-like microspheres was facilely accomplished through a sim- ple protocol involving regulation of pH value in aqueous with sodium hydroxide in the presence of n-propanol. The as-prepared samples were characterized by a collection of techniques, such as X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersive X-ray spectroscopy (EDX), UV-vis diffuse reflectance spectroscopy (UV-vis DRS), and nitrogen adsorption-desorption isotherms. Based upon the SEM analyses, uniform microspheres could be formed with coexistence of some fragments of BiOCI nanosheets without n-propanol. The addition of appropriate amount of n-propanol was beneficial to provide BiOCI samples containing only flower-like microspheres, which were further subjected to the photocatalytic measurements towards Rhodamine B in aqueous under visible light irradiation and exhibited the best catalytic performance among all samples tested. In addition, the photocatalytic process was confirmed to undergo through a photosensitization pathway, in which superoxide radicals (.O-) played critical roles. PMID- 26353667 TI - Synthesis of Surface-Enhanced Raman Scattering-Active Gold Nanoflowers by 5 Hydroxytryptophan in Acidic Solution. AB - We demonstrated a one-step synthesis of gold nanoflowers by 5-hydroxytryptophan (5-HTP) in acidic solutions at room temperature. The synthesized nanoflowers are 400 nm in dimension consisting of a solid core and many small petal-like nanoparticles (30-50 nm) in various directions. The shape, size and surface morphology of the gold nanostructure could be tuned by controlling the molar ratio of 5-HTP to HAuCl4 and HCl concentration. Examination of the nanoparticles at different reaction stages with transmission electron microscopy (TEM) reveals the shape evolutionary process of the nanoflowers to get a better understanding on their possible formation mechanism. Additionally, these gold nanoflowers exhibit a high SERS performance because of textured surface which is expected to provide many active sites. PMID- 26353668 TI - Carbazole-Functionalized Organic Photosensitizer for Dye-Sensitized Solar Cells. AB - We designed and synthesized the photosensitive pi-conjugated organic dyes (CB-1, CB-2 and CB-3) with the carbazole substituted triphenylamine moiety as an electron donor unit and the cyanoacetic acid moiety as an acceptor for the application as a photosensitizer of dye-sensitized solar cells. The dyes with two carbazole units connected to triphenylamine moiety (CB-2 and CB-3) showed enhanced electron donating property than the one with one carbazole moiety as an electron donor unit (CB-1), which resulted in longer absorption maximum wavelength, higher overall photon to current conversion efficiency and IPCE values. In particular, CB-3 showed an absorption maximum wavelength at 428 nm and overall solar-to-energy conversion efficiency of 7.58% at AM 1.5 illumination (100 mW.cm-2) without mask. PMID- 26353669 TI - Preparation and Electrochemical Properties of Polyaniline Composite Electrodes Prepared by In-Situ Polymerization in Hydrous Ruthenium Oxide Dispersed Aqueous Solution. AB - Polyaniline (PANI)/ruthenium oxide (RuO2) composites were prepared by a chemical oxidation polymerization with various amount of hydrous RuO2. In the PANI/RuO2 composites, RuO2 particles were surrounded by PANI. The morphology and structure of the PANI/RuO2 composites were examined by field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), and X-ray diffraction (XRD). Analysis by TEM revealed that the aggregations of the composites were increased with the amounts of hydrous RuO2. Electrochemical performances of prepared composites were characterized by cyclic voltammetry (CV). The composites prepared with 20 wt% of hydrous RuO2 per aniline monomer showed the highest specific capacitance of 710 F/g at 5 mV/s among the prepared composites. However, the specific capacitance of the composites with excess amounts of hydrous RuO2 is lower than the highest one. The large aggregation of RuO2 particles prevents the participation in electrochemical reaction due to the long pathway from the electrolyte and a decrease of effective surface area. PMID- 26353670 TI - Magnetization and Magnetocaloric Effect in Sol-Gel Derived Nanocrystalline Copper Zinc Ferrite. AB - We report the sol-gel synthesis and magnetocaloric effect in nanocrystalline copper-zinc ferrite (Cu0.5Zn0.5Fe2O4). The synthesized powder was characterized by using X-ray diffraction (XRD), field emission scanning electron microscopy (FE SEM), energy dispersive X-ray spectroscopy (EDX) and magnetization measurements. The XRD results confirm the formation of single phase spinel structure. The average particle size was found to be ~58 nm. FE-SEM results suggested that the nanoparticles are agglomerated and spherical in shape. Magnetization measurement reveals that Cu0.5Zn0.5Fe2O4 nanoparticles exhibit transition temperature (Tc) above room temperature. The maximum magnetic entropy change (DeltaSM)max shows interesting behaviour and was found to vary with the applied magnetic field. This nanopowder can be considered as potential material for magnetic refrigeration above room temperature. PMID- 26353671 TI - High Density of Line Pattern by Using De-Wetting During Soft-Lithography. AB - Here we prepared highly reliable and high density of pattern by using de-wetting induced soft-lithography. Additional line pattern arising from de-wetting of PS is generated in the protrusion of poly-dimethyl-siloxane (PDMS) mold by controlling thermal annealing time and molecular weight of PS. We found that such de-wetting and pattern formation is not dependent on the PS film thickness, but strongly influenced by molecular weight and annealing time of PS. These results indicate that high molecular weight of PS with such circumstance suppresses the mobility of the polymer chain, enhancing the surface tension of the polymer. We demonstrate that these de-wetting induced patterns attributed to the change of the mobility and the surface tension of PS chains, creating a high density of patterns with high reproducibility. PMID- 26353672 TI - Effect of Stepwise Doping on Lifetime and Efficiency of Blue and White Phosphorescent Organic Light Emitting Diodes. AB - We investigated a light emission mechanism of blue phosphorescent organic light emitting diodes (PHOLEDs), using a stepwise doping profile of 2, 8, and 14 wt.% within the emitting layer (EML). We fabricated several blue PHOLEDs with phosphorescent blue emitter iridium(III) bis[(4,6-difluorophenyl)-pyridinato N,C2]picolinate doped in N,N'-dicarbazolyl-3,5-benzene as a p-type host material. A blue PHOLED with the highest doping concentration as part of the EML close to an electron transporting layer showed a maximum luminous efficiency of 20.74 cd/A, and a maximum external quantum efficiency of 10.52%. This can be explained by effective electron injection through a highly doped EML side. Additionally, a white OLED based on the doping profile was fabricated with two thin red EMLs within a blue EML maintaining a thickness of 30 nm for the entire EML. Keywords: Blue Phosphorescent Organic Light Emitting Diodes, Stepwise Doping Structure, Charge Trapping Effect. PMID- 26353673 TI - Relationship Between Structural, Morphological, Optical and Magnetic Properties of Transition Metal (TM)-Doped ZnO Nanostructures Prepared by Microwave Hydrothermal. AB - In this work, pure and 3% TM (Co, Ni, and Cu)-doped ZnO nanostructures were prepared by microwave-hydrothermal method. The striking similarities between changes in the lattice volume, bandgap energy, morphology and saturation magnetization indicated a strong correlation between these properties. XRD, SAED and HRTEM analyses revealed that all the TM-doped ZnO nano-structures have wurtzite structure and no secondary phase was detected. FESEM and TEM results confirmed a higher aspect ratio and highly crystalline nature of nanostructures. Raman spectra revealed that no defect related mode was observed which indicated that the nanostructures have high quality and negligible defects. The value of bandgap was found to decrease with the increase in atomic number of TM dopants. RTFM was observed in all the TM-doped ZnO nanostructures and the value of Ms and Mr were decreased with TM dopants. PMID- 26353674 TI - Sodium Hydroxide Activated Nanoporous Carbons Based on Lapsi Seed Stone. AB - Nanoporous activated carbons (ACs) were prepared from Lapsi (Choerospondias axillaris) seed powder by chemical activation with sodium hydroxide (NaOH) at different NaOH impregnation ratios. The prepared ACs were characterized by Fourier transform-infrared (FTIR) spectroscopy, Raman scattering, X-ray diffraction (XRD), and scanning electron microscopy (SEM). Semi-quantitative information on the surface properties was obtained by estimating iodine number. FTIR spectra showed the presence of oxygenated functional groups such as hydroxyl, carbonyl, and carboxyl in the prepared ACs. Raman scattering showed clear D and G bands in the spectra. The intensity ratio of G and D band peak intensity was ca. 1.39 at lowest NaOH and Lapsi seed powder ratio 0.25:1 showing high graphitic degree. This ratio decreased with increase in the NaOH impregnation ratio and reached minimum ca. 0.94 (comparable with commercial AC) at NaOH and Lapsi seed powder ratio 1:1 demonstrating that higher NaOH impregnation reduces the graphitic structure of the carbon. XRD patterns showed two broad peaks at diffraction angles of approximately 25 and 43 degrees indicating the amorphous structure. Surface properties of the ACs (BET surface area, pore volume, and pore size distributions) were evaluated by nitrogen adsorption-desorption isotherm. Our ACs showed strong methylene blue adsorption property (maximum methylene blue is ca. 200 mg/g). Judging from the iodine number and methylene blue values, structure, and surface areas, it can be concluded that NaOH impregnation ratio is one of the key parameters to tune the surface properties of Lapsi seed stone-based activated carbons. PMID- 26353675 TI - Evaluation on the Toxic Effects of NanoAg to Catalase. AB - Protein is the functional actor of life. Research on protein damage induced by nanomaterials may give insight into the toxicity mechanisms of nanoparticles. Studying nano silver over the impact of the structure and function of catalase (CAT) at the molecular level, is of great significance for a comprehensive evaluation of their toxic effects. The toxic effects of nanoAg on catalase were thoroughly investigated using steady state and time resolved fluorescence quenching measurements, ultraviolet-visible absorption spectroscopy, resonance light scattering spectroscopy (RLS), circular dichroism spectroscopy (CD) and transmission electron microscopy (TEM). NanoAg could decrease the amount of alpha helix and increase the beta sheet structure, leading to loose the skeleton structure of catalase. The characteristic fluorescence of catalase was obviously quenched, which showed the exposal of internal hydrophobic amino acids enhanced, and its quenching type is dynamic quenching. The result of RLS and TEM showed that the distribution and size of nanoAg become more uniform and smaller after their interaction, resulting in a decrease of RLS intensity. NanoAg could make the activity of catalase rise. By changing the structure of catalase, nanoAg increases its enzymatic activity to a certain extent, breaking down its balance in vivo, thereby affecting the normal physiological activities. NanoAg has obvious toxic effects on catalase. This paper provided a new perspective and method for the toxic effects of nanoAg to biological macromolecules; provided basic data and reference gist for the hygienics and toxicology studies of nanoAg. It is conducive to the toxicity prevention and control work of nanoAg, promoting nano-technology applied to human production and living better. PMID- 26353676 TI - Simple and Sensitive Colorimetric Assay for Pb2+ Based on Glutathione Protected Ag Nanoparticles by Salt Amplification. AB - A simple and sensitive colorimetric assay for Pb2+ detection has been reported using glutathione protected silver nanoparticles (AgNPs) by salt amplification. The naked AgNPs aggregate under the influence of salt. Glutathione (GSH) can bind to AgNPs via Ag-S bond, helping AgNPs to against salt-induced aggregation. However, GSH binding to AgNPs can be compromised by the interaction between Pb2+ and GSH. As a result, Pb2+-mediated aggregation of AgNPs under the influence of salt is reflected by the UV-Visible spectrum, and the qualitative and quantitative detection for Pb2+ is accomplished, with the detection range 0.5-4 uM and a detection limit of 0.5 uM. At the same time, Pb2+ in real water sample is detected. Furthermore, the high selectivity and low cost of the assay means it is promising for enviromental applications. PMID- 26353677 TI - Low-Voltage InGaZnO Thin Film Transistors with Small Sub-Threshold Swing. AB - We demonstrate a low-voltage driven, indium-gallium-zinc oxide thin-film transistor using high-kappa LaAlO3 gate dielectric. A low VT of 0.42 V, very small sub-threshold swing of 68 mV/dec, field-effect mobility of 4.1 cm2/Ns and low operation voltage of 1.4 V were reached simultaneously in LaAlO3/IGZO TFT device. This low-power and small SS TFT has the potential for fast switching speed and low power applications. PMID- 26353678 TI - Enhanced Photocatalytic Activity of as-Prepared Sodium Titanates for m Dinitrobenzene Reduction and Sulfosulfuron Oxidation. AB - This paper demonstrates the preparation and photocatalytic activity of sodium titanate nanorods and nanotubes prepared by hydrothermal method using P25-TiO2 as the precursor. XRD results confirmed the monoclinic structure of sodium titanate nanorods obtained after calcinations of orthorhombic sodium titanate nanotubes at 800 degrees C for 2 h. The BET surface area of sodium titanate nanotubes (176 m2 g-1) was significantly reduced for sodium titanate nanorods (21 m2 g-1) formation because of the collapsing of the hollow interior of the former during its high temperature sintering. The selective formation of m-diaminobenzene by the photoreduction of the m-dinitrobenzene was found to be comparable by sodium titanate nanorods (89.5 +/- 0.5%) and P25-TiO2 (98.2 +/- 0.8%), whereas Au deposition (0.5 and 2 wt%) onto sodium titanate nanorods notably altered the products (m-nitroaniline and m-diaminobenzene) distribution after 8 h of UV-light irradiation and which was confirmed later by GC-MS analysis. This high photoactivity of as-prepared nanorods could be credited to better delocalization and longer relaxation lifetime (68 us) of photoexcited e-/h+ pairs along the length of crystalline sodium titanate nanorods than P25-TiO2 (45 us) as measured from Time-resolved spectroscopy. The photooxidation of sulfosulfuron herbicide (1000 ppm) and corresponding CO2 formation was found to be highest with sodium titanate nanotubes due to the presence of more hydroxyl groups over the largest surface area that dominates over its least relaxation lifetime (41 us). PMID- 26353679 TI - Optimum Thickness Conditions of TiO2 Nanotubes Layer for Efficient Electrochemical Luminescence Cells Application. AB - We report a TiO2 nanotubes (NTs)-based Electrochemical luminescence (ECL) cell. The ECL cell was fabricated using the electrode of TiO2 NTs and Ru(II) complex (Ru(bpy)2+(3)) as a luminescence materials. The fabricated ECL cell is composed of F-doped SnO2 (FTO) glass/Ru(II)/TiO2 NTs/Ti plate. At a bias voltage of 3 V, the measured ECL efficiencies were 0 Im/W for cell without NTs, 0.03 Im/W for NTs 6.5 um, 0.07 Im/W for NTs-8 um and 0.1 Im/W for NTs-10 um, respectively. The use of Ti02 NTs increases ECL intensities by about 2 times compared to the typical ECL cell without the use of TiO2 NTs. PMID- 26353680 TI - Increased Photovoltaic Performance in Polymer-Oligothiophene-[6,6]-Phenyl-C61 Butyric Acid Methylester Ternary Blend Films. AB - The introduction of oligothiophenes (b-5T and b-5TB) improved the performance of F85TB:PCBM bulk heterojunction OPV cells due to improved UV-vis absorption and the well-matched cascade energy levels between components. PMID- 26353681 TI - Efficiency Improvement of Dye-Sensitized Solar Cells with Surface-Modified Photoelectrodes. AB - A novel surface modifier, ethylenediamine tetraacetic acid tetrasodium salt (EDTNa), was incorporated on the surface of TiO2, and the resulting electrodes were applied to the photoanode of dye-sensitized solar cells (DSSCs). The DSSC with EDTNa-incorporated photoelectrode showed an increase in short-circuit current (JSC) and open-circuit voltage (VOC), resulting in a 16.5% enhancement in power conversion efficiency, compared to that of reference cell without EDTNa. It was found that the presence of the bulky ethylenediamine tetraacetate moieties increases lifetime of electrons injected from dye molecules to TiO2, resulting from an effective prevention of direct contact between electrolyte ions and the TiO2 surface. This improvement of lifetime induced the enhancement in J, and VOC. PMID- 26353682 TI - Two Dimensional Aggregation Behaviors of Quinoxaline Dendrimers. AB - This study focuses on the molecular behavior of two dendrimers containing a hydrophilic core group (carboxyl group) and hydrophobic branches (quinoxaline and methoxyphenyl groups), 2,3-bis(4-(2,3- bis(4-methoxyphenyl)quinoxalin-6 yloxy)phenyl)quinoxaline-6-carb-oxylic acid (G2) and 2,3-bis(4-(2,3-bis(4-(2,3 bis(4-methoxyphenyl)quinoxalin-6-yloxy)phe-nyl)quinoxalin-6-y-oxy)phenyl) quin oxaline-6-carboxylic acid (G3) at the air-water interface. To understand the mechanism of the self-assembly of these molecules, we measured the surface pressure-area (III-A) isotherm and investigated the surface morphology of Langmuir-Blodgett films transferred onto hydrophilic silicon wafers using atomic force microscopy (AFM). Upon compression, G2 molecules stand up and steadily make close-packed monolayer whereas G3 molecules form circular domains and gradually make aggregates of domains. These results were confirmed by the X-ray Reflectivity (XRR) profiles of G2 and G3 monolayers transferred onto silicon substrates. PMID- 26353683 TI - Semiconducting Polymers Consisting of Anthracene and Benzotriazole Units for Organic Solar Cells. AB - An alternating copolymer composed of 2,6-dibromo-9,10-bis(2 ethylhexyloxy)anthracene and benzotriazole units, poly(An-alt-BTz), was synthesized, through a Suzuki cross-coupling polymerization, for use in photovoltaic devices as a p-type electron donor. For the reduction of the bandgap energy of benzotriazole units, 5,5'-dibromo-2,2'-bithiophene, or 2,5 dibromothieno [3,2-b] thiophene units were introduced into the polymer. Poly(anthracene-co-benzotriazole-co-bithiophene(thienothiophene))s were synthesized using the same polymerization reactions. The measured optical bandgap energy of poly(anthracene-alt-benzotriazole) was 2.62 eV. As the contents of the flat comonomer units in the ter-polymers increased, the bandgap energies of the resulting polymers decreased up to 1.95 eV. The energy levels of the HOMO and the LUMO of the copolymers were determined from the cyclic voltammetry. Photovoltaic devices were fabricated with the polymers as electron donors and PC71 BM as an electron acceptor. One of the fabricated devices showed the maximum PCE of 0.74% with 0.57 V of VOC, 2.59 mA/cm2 of JSC, and 0.48 of FF under AM 1.5G (100 mW/cm2) condition. PMID- 26353684 TI - Energy Antenna for Efficient Dye-Sensitized Solar Cells. AB - In this study, we investigated the effect of the placement of acceptor in dual donor based dye sensitizers (TPA-PTZ-CN, PTZ-TPA-CN). Triphenylamine (TPA) and phenothiazine (PTZ) are well known as electron donors and cyanoacetic acid (CN) is a known electron acceptor. The absorption spectrum of the dyes showed different form because of the different energy levels of molecular orbital (MO) of each dye and intramolecular energy transfer (EnT). The absorption spectrum of PTZ-TPA-CN was broader than that of TPA-PTZ-CN and its molar extinction coefficient was also higher than TPA-PTZ-CN. Because of its enhanced panchromatic absorption spectra, PTZ-TPA-CN showed better photovoltaic properties than the other dyes did. This work presents that optimizing the placement of acceptor in dual donor based dye would give good photovoltaic properties for dye-sensitized solar cells (DSSC). PMID- 26353685 TI - Effects of Titanium Doping Concentration on the Structural and Electrical Properties of Sputtered Indium Oxide Films. AB - The surface structure and electrical properties of titanium-doped indium oxide (ITiO) films prepared by RF magnetron sputtering were investigated. The doping concentration of TiO2 in the In2O3 target was changed from 1.0 wt.% to 10.0 wt.% with increments of 1.0 wt.%. At a Ti content of 5.0 wt.%, the optimum growth conditions were achieved. The finest value of hall mobility, carrier concentration, and resistivity of the deposited film reached 47.03 cm2Ns, 1.148 x 10(21) cm-3 and 1.14 x 10(-4) Omegacm, respectively. Then the transmittance was achieved up to 82% at 570 nm. The peaks of the XRD spectra became more intense and sharp as the Ti concentration increased up to 2.5 wt.% but a higher Ti content of 10.0 wt.% retarded a growth of In2O3 grains. The surface roughness of the films by examination of surface morphology using AFM also rose with increase of Ti doping concentration. PMID- 26353686 TI - Preparation of Carbon-Doped TiO2 and Its Application as a Photoelectrodes in Dye Sensitized Solar Cells. AB - In this study, C-doped TiO2 particles were successfully synthesized by a hydrothermal method. Three binding energy peaks were observed at 284.6, 286.2, and 288.5 eV in the C is region of the XPS. The signals at 286.2 and 288.5 eV were attributed to chemically bound C-O and Ti-C-O linkages within the crystalline TiO2 lattice, respectively. The introduction of carbon did not affect the crystallite structure or BET surface area of TiO2. The JSC value of DSSCs based on a C-doped TiO2 electrode was increased by 20% compared to DSSCs using a pure TiO2 electrode, and the energy conversion efficiency was increased by 23%. This was due to the enhancement of dye adsorption and high electrical conductivity of the carbon. High energy conversion efficiency was achieved with the DSSCs based on the C-doped TiC2 electrode. PMID- 26353687 TI - Catalytic Activity of Gold Nanoparticles Immobilized Onto Single-Walled Carbon Nanotubes Using N,N'-Bis(2-pyridylmethyl)-2-Hydroxyethylamine. AB - Au NPs were immobilized onto the surface of single-walled carbon nanotubes (SWCNTs) via covalent functionalization of SWCNTs using N,N'-bis(2-pyridylmethyl) 2-hydroxyethylamine (BPMEA-OH), which was confirmed by Fourier transform infrared spectroscopy. The morphology of the resulting SWCNTs/Au NPs composites was observed by transmission electron microscopy and field emission scanning electron microscopy with X-ray microanalysis. The catalytic activity of SWCNT/Au NPs was investigated by UV-Vis absorption measurements. PMID- 26353688 TI - Synthesis and Characterization of Hydroxyapatite/Fullerenol Nanocomposites. AB - Fullerenols are polyhydroxylated, water soluble derivatives of fullerene C60, with potential application in medicine as diagnostic agents, antioxidants or nano drug carriers. This paper describes synthesis and physical characterization of a new nanocomposite hydroxyapatite/fullerenol. Surface of the nanocomposite hydroxyapatite/fullerenol is inhomogeneous with the diameter of the particles in the range from 100 nm to 350 nm. The zeta potential of this nanocomposite is ten times lower when compared to hydroxyapatite. Surface phosphate groups of hydroxyapatite are prone to forming hydrogen bonds, when in close contact with hydroxyl groups, which could lead to formation of hydrogen bonds between hydroxyapatite and hydroxyl groups of fullerenol. The surface of hydroxyapatite particles (-2.5 mV) was modified by fullerenol particles, as confirmed by the obtained zeta potential value of the nanocomposite biomaterial hydroxyapatite/fullerenol (-25.0 mV). Keywords: Hydroxyapatite, Fullerenol, Nanocomposite, Surface Analysis. PMID- 26353689 TI - Can Be a Bimetal Oxide ZnO-MgO Nanoparticles Anticancer Drug Carrier and Deliver? Doxorubicin Adsorption/Release Study. AB - Bimetal oxide ZnO-MgO nanoparticles were synthesised by precipitation method at low temperature and characterised by analytical techniques such as XRD, SEM and FT-IR. In order to know the efficiency of uptake and release of anticancer drug, the adsorption and release of doxorubicin, on bimetal oxide nanoparticles was performed in dark room at room temperature. The adsorption models such as Henry, Freundlich and Langmuir models were validated with obtained experimental data. Due to heterogeneous surface of bimetal oxides, data followed well with Henry and Freundlich models but not Langmuir that proposed homogeneous adsorbent surface. The strong affinity between drug and nanoparticles is certainly due to the electrostatic interaction between positively charged doxorubicin molecules and negatively charged surface of ZnO-MgO nanoparticles and hydrogen bonding between them that confirmed from FT-IR analysis. The doxorubicin release from ZnO-MgO nanoparticles was performed at pH 4 and 7 to evaluate the kinetic of drug release using various mathematical models. At neutral pH, the doxo release was found to be ~14% whereas at acidic pH (pH 4) nearly 68% of doxo was released at 6.5 hours due to dissolution and neutralising the surface charge of ZnO-MgO nanoparticles. Various mathematical models such as zero order, first order, Higuchi and Hixson Crowell were approached to evaluate the kinetic release of drug from the nanoparticles. The obtained release data for acidic pH followed Hixson-Crowell model, proposes erosion dependent release system, compared to Higuchi that confirmed doxo release is due to dissolution of ZnO-MgO nanoparticles. In this study, it is concluded that ZnO-MgO nanoparticles will be a promising drug vehicle in drug delivery system. PMID- 26353690 TI - Differential Expression of miRNAs Under Salt Stress in Spartina alterniflora Leaf Tissues. AB - Coastal marsh habitats are impacted by many factors or disturbances, including habitat destruction, pollution, and the introduction of invasive species. Spartina alterniflora (S. alterniflora) is an important invasive species, accounting for a significant proportion of the invasive plants spread around the world. Salt stress is a major environmental stress factor, which affects plant growth and development. Little information is available regarding S. alterniflora microRNAs (miRNAs) which play important regulatory roles in plant growth and development. In order to detect S. alterniflora miRNAs and determine any expression differences between S. alterniflora plants cultivated on ordinary soils from the greenhouse and salty soils from Dafeng, in Jiangsu province of China, we carried out the detection and quantification of S. alterniflora miRNAs by microarray. Among the 81 miRNAs identified as significantly down- or up regulated under the salt stress, 21 of the miRNAs represent 8 miRNA gene families in S. alterniflora. We found that miR168, miR399, miR395, miR393, miR171, miR396, miR169, and miR164 were down-regulated under salinity stress, and 60 of the miRNAs were up-regulated, which were revealed to be induced by salt stress in plants. The identification of differentially expressed novel plant miRNAs and their target genes, and the analysis of expression, provide molecular evidence for the possible involvement of miRNAs in the process of salt response and/or salt tolerance in S. alterniflora. PMID- 26353691 TI - Highly Luminescent Hybrid SiO2-Coated CdTe Quantum Dots Retained Initial Photoluminescence Efficiency in Sol-Gel SiO2 Film. AB - A highly luminescent silica film was fabricated using tetraethyl orthosilicate (TEOS) and 3-aminopropyltrimethoxysilane (APS) through a controlled sol-gel reaction. The pre-hydrolysis of TEOS and APS which resulted in the mixture of TEOS and APS in a molecular level is a key for the formation of homogenous films. The aminopropyl groups in APS play an important role for obtaining homogeneous film with high photoluminescence (PL). Red-emitting hybrid SiO2-coated CdTe nano crystals (NCs) were fabricated by a two-step synthesis including a thin SiO2 coating via a sol-gel process and a subsequent refluxing using green-emitting CdTe NCs. The hybrid SiO2-coated CdTe NCs were embedded in a functional SiO2 film via a two-step process including adding the NCs in SiO2 sol with a high viscosity and almost without ethanol and a subsequent spinning coating. The hybrid SiO2 coated CdTe NCs retained their initial PL efficiency (54%) in the film. Being encapsulated with the hybrid NCs in the film, no change on the absorption and PL spectra of red-emitting CdTe NCs (632 nm) was observed. This indicates the hybrid NCs is stable enough during preparation. This phenomenon is ascribed to the controlled sol-gel process and a hybrid SiO2 shell on CdTe NCs. Because these films exhibited high PL efficiency and stability, they will be utilizable for potential applications in many fields. PMID- 26353692 TI - Crystalline Silver Nanoparticles by Using Polygala tenuifolia Root Extract as a Green Reducing Agent. AB - Due to the emergence of multidrug-resistant bacteria, silver nanoparticles (AgNPs) have found interest as a new category of antibacterial agents. The toxicity of the chemicals involved in the commonly employed chemical methods for synthesizing AgNPs present limitations for subsequent pharmaceutical and biomedical applications. In this report, 70% aqueous ethanol extracts of Polygala tenuifolia root were used to reduce Ag+1 ions for AgNPs synthesis. The as synthesized AgNPs were characterized via UV-Visible spectrophotometry, high resolution transmission electron microscopy, atomic force microscopy, X-ray diffraction, and Fourier transform infrared spectroscopy. A strong surface plasmon resonance band was observed at 414 nm. Images from the high resolution transmission electron microscopy and atomic force microscopy demonstrated the spherical and irregular shapes of the AgNPs were synthesized. The AgNP crystalline structure was confirmed by the strong diffraction peaks in the X-ray diffraction results and by the bright circular spots observed in selected-area electron diffraction, whose average diameter was measured to be 17.97 8.63 nm or 15.12 nm via high resolution transmission electron microscopy images or X-ray diffraction analysis, respectively. The as-synthesized AgNPs exerted the highest antibacterial activity against Escherichia coli among the tested Gram-positive and Gram-negative bacteria. The current method is eco-friendly, straightforward, cost-effective, biocompatible, and easily scaled up to produce of AgNPs for applications in the treatment of bacterial infections. PMID- 26353693 TI - Simple Recovery of Intracellular Gold Nanoparticles from Peanut Seedling Roots. AB - Fabrication of inorganic nanomaterials via a biological route witnesses the formation either extracellularly, intracellulary or both. Whereas extracellular formation of these nanomaterials is cherished owing to their easy and economical extraction and purification processes; the intracellular formation of nanomaterials, due to the lack of a proper recovery protocol has always been dreaded, as the extraction processes used so far were tedious, costly, time consuming and often resulting in very low recovery. The aim of the present study was to overcome the problems related with the extraction and recovery of intracellularly synthesized inorganic nanoparticles, and to devise a method to increasing the output, the shape, size, composition and dispersal of nanoparticles is not altered. Water proved to be much better system as it provided well dispersed, stable gold nanoparticles and higher recovery. This is the first report, where intracellular nanoparticles have been recovered using a very cost-effective and eco-friendly approach. PMID- 26353694 TI - Synthesis of Nanocrystalline SnO2 Microspheres and Their Hydrogen Absorption Characteristics. AB - SnO2 solid microspheres and multilayered nanocrystalline SnO2 hollow microspheres (MHS-SnO2) have been successfully synthesized in the solvothermal environment by using different solvents. The morphology, structure and composition of the as prepared products are characterized by field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), high resolution transmission electron microscopy (HRTEM) with selected area electron diffraction (SAED) and X-ray diffraction (XRD). The growth mechanism of SnO2 solid microspheres and MHS-SnO2 are proposed and attributed to the viscosity of solvent. The studies on hydrogen absorption characteristics of SnO2 solid structure and MHS-SnO2 show an absorption capability of 0.50 wt.% and 0.92 wt.%, respectively. PMID- 26353695 TI - Strong Magnetoelectric Coupling of Pb1-xSrx(Fe0.012Ti0.988)O3 Nanoparticles. AB - Pb1-xSrx(Fe012Ti0.988)O3 (PSFT) nanoparticles were prepared by a chemical synthesis using polyvinyl alcohol as surfactant. X-ray diffraction pattern has been used to analyze the phase structure and average particles size. Transmission electron microscopy is used to confirm the nano size of the PSFT particles. The magnetoelectric (ME) coupling is observed at room temperature by measuring the ME coefficient (alphaE) as the function of applied dc magnetizing field under the influence of ac magnetic field of 2 Oe and frequency 800 Hz. The maximal value of alphaE is observed in PSFT3. The ME coupling is also studied by observing the variation of polarization hysteresis measured in the presence of zero and 0.2 T of external magnetic field. PMID- 26353696 TI - Quantitative Replacement of Citrate by Phosphane on Silver Nanoparticle Surfaces Monitored by Surface-Enhanced Raman Spectroscopy (SERS). AB - Chemical approaches to metal NP synthesis commonly use capping agents to achieve a desired NP size and shape. Frequently, such NPs require chemically different surface ligands after synthesis to generate desired NP properties (e.g., charge or hydrophilicity) and to increase their long term colloidal stability. Here, we prepared SERS active citrate-stabilized silver NPs (d = 38+/-4 nm), purified them from remaining reactants by ultracentrifugation and redispersion, and immersed them into solutions containing different concentrations of Tris(sodium-m sulfonatophenyl)phosphine (TPPTS), which is often used in such ligand replacement approaches to increase colloidal stability. After equilibration, SERS spectra were acquired, elucidating the concentration dependence of the ligand replacement reaction. SERS data were complemented by concentration dependent size measurements and relations between ligand exchange and colloidal stability are discussed. PMID- 26353697 TI - One-Step Immobilization of Initiators for Surface-Initiated Ring Opening Polymerization and Atom Transfer Radical Polymerization by Poly(norepinephrine) Coating. AB - We report a facile method for surface-initiated ring opening polymerization (ROP) and atom transfer radical polymerization (ATRP) via a poly(norepinephrine) coating. Solid substrates were modified by poly(norepinephrine) under alkaline conditions, with concurrent co-adsorption of an ATRP initiator. The poly(norepinephrine) layer acted as a ROP initiator due to the presence of hydroxyl groups in its side chain, resulting in a surface that was able to initiate ATRP and ROP simultaneously. epsilon-Caprolactone (epsilon-CL) and 2 (dimethylamino)ethyl methacrylate (DMAEMA) were grafted onto the surface via ROP and ATRP, respectively, and the polymers subsequently grown from the surfaces were characterized in detail using Fourier transform infrared (FT-IR) spectroscopy, X-ray photoelectron spectroscopy (XPS), contact angle goniometry, and atomic force microscopy (AFM). PMID- 26353698 TI - The Properties of Cu Thin Films on Ru Depending on the ALD Temperature. AB - The copper thin films were deposited by Atomic layer deposition (ALD) on a ruthenium depending on the substrate temperatures. The substrate deposited Ru and TaN on SiO2 by plasma enhanced ALD (PEALD) before Cu deposition for an adhesion layer between Si and Cu. The copper thin films were deposited 200 cycles. The thickness of Cu was different depending on the substrate temperatures. The properties of copper thin films were investigated by a 4 point probe, SEM, and AFM. TaN and Ru layers were deposited by plasma enhanced ALD (PEALD) for the adhesion layer. Also, TaN and Ru layers were observed as TEM because the thickness was too thin. The thickness and roughness of Cu thin film increased depending on the deposition temperatures but, Cu thin film was not deposited at 110 degrees C. The best sheet resistance of the copper thin film was obtained at a deposition temperature of 170 degrees C. PMID- 26353699 TI - Fabrication, Structure, and Gas Sensing of Multiple-Networked Pt-Functionalized Bi2O Nanowires. AB - Bi2O3 is highly sensitive to low concentrations of NO2 in ambient air and are almost insensitive to most other common gases. However, it still remains a challenge to enhance their sensing performance and detection limit. This study examined the influence of the functionalization of Bi2O3 nanorods with Pt on the NO2 gas sensing properties. Pt-functionalized beta-Bi2O3 nanorods were fabricated by the thermal evaporation of Bi powder followed by sputter-deposition of Pt and annealing. The Pt-functionalized nanorods ranged from 100 to 300 nm in diameter and from a few tens to a few hundreds of micrometers in length. Multiple networked Pt-functionalized beta-Bi2O3 nanorod sensors showed the responses of ~141 to ~313% at 1-5 ppm NO2 at 300 degrees C. These response values were 1.23 1.93 times higher than those of pristine Bi2O3 nanorod sensors at 1-5 ppm NO2. The origin of the enhancement of the sensing properties of the Bi2O3 nanorods by Pt functionalization is discussed. PMID- 26353700 TI - Electrochemical Analysis of Polyethyleneimine- Conductive Carbon Black Supports for Pt-Pd Electrocatalysts. AB - Pt-Pd nanocomposite supported on polyethylenimine-functionalized carbon black (Pt Pd/PEl-CB) was reported. Pt-Pd nanoparticles are supported on PEI-CB composite by chemical reduction of H2PtCl6 and PdCl2 using a polyol method. The concentration of Pt-Pd alloyed metals on CB was adjusted to 20 wt%. The physical properties of nanocomposites were investigated by transmission electron microscopy (TEM) and X ray diffraction (XRD), respectively. The electrochemical properties of Pt-Pd nanocomposites were confirmed by cyclic voltammetries (CVs). The fundamental electrochemical test results indicated that the electrocatalytic activities of a PEI-CB supported Pt-Pd nanocomposite were better than pristine CB supported Pt-Pd nanocomposite, which was attributed to the increase of the conductivity and the facile removal of intermediate poisoning species with the aid of Pt-Pd. PMID- 26353701 TI - Enhancement of Photo-Current Conversion Efficiency in a CdS/CdSe Quantum-Dot Sensitized Solar Cell Incorporated with Single-Walled Carbon Nanotubes. AB - Cadmium sulfide (CdS) and cadmium selenide (CdSe) are sequentially assembled onto a nanocrystalline TiO2 film to create a quantum-dot (QD)-sensitized solar cell application by a successive ionic layer adsorption and reaction (SILAR) method. The results show that CdS and CdSe QDs have a complementary effect in the performance of light harvest of solar cell. Single-walled carbon nanotubes (SWNTs) are incorporated with a CdS/CdSe QDs solar cell by mixing them with TiC2 film to enhance electron transfer. SWNTs are also sprayed onto CdSe QDs (SWNTs onto CdSe) to apply p+ type properties of SWNTs. Absorbance is increased in a wide wavelength range. In particular, cells having the sprayed SWNTs onto the QDs show a clear increase in absorbance at a low wavelength region. The fill factor of CdS/CdSe QDs solar cell with SWNTs is higher than that without SWNTs, indicating the decrease in loss of electron from TiO2 to QDs. Short-circuit current in a QD-sensitized solar cell having SWNTs on CdSe shows maximum value. Photo-current conversion efficiency of cells is increased in both cell types containing SWNTs at 10~17% compared with pristine cells. We expect that solar cells using SWNTs will affect future energy technology and devices. PMID- 26353702 TI - A Microreactor System for Cultivation of Haematococcus pluvialis and Astaxanthin Production. AB - Development of efficient culture and monitoring system for cell growth and production of useful materials is required for practical utilization of microalgae. In the present study, we developed a PDMS-based microreactor system for efficient, rapid culture of microalgae and monitoring of cell growth, carotenoid content under diverse culture conditions. Due to advantages of PDMS, we optimized culture conditions (light intensity, pH, nitrate depletion, carbon dioxide concentration) for improving growth rate and astaxanthin productivity in considerably less time compared to conventional culture methods using flask or well plate. In addition, we found that there was a strong linear correlation between fluorescence intensity of astaxanthin stained by Nile red and the astaxanthin content, which can be utilized as a high-throughput screening tool in microfluidic systems. In this study, the growth rate of vegetative Haematococcus pluvialis was improved by 60% in microfluidic chamber than in flask and astaxanthin was produced up to 362 mg/L under the optimal conditions (300 umol photon/m2/s of light, 7% CO2 (v/v), and pH 7.0) using designed microfluidic devices. This result shows that microfluidic system can provide effective means to address development of microalgal strains including H. pluvialis and bioprocess. PMID- 26353703 TI - Tunable Photonic Band Gap of PS-b-P2VP Lamellar Film Using Metal Ions and pH Gradation. AB - Optical properties of photonic crystal film were investigated by tuning photonic band gap (PBG). The lamellar-forming photonic films were prepared by nearly symmetric poly(styrene-b-2-vinyl pyridine) (PS-b-P2VP) block copolymers. Molecular weight of PS block and P2VP block is 52 kg/mol, and 57 kg/mol, respectively. When submerged in water, the lamellar films were swollen and show Bragg reflection in visible light region. We observed that the reflection color can be tuned by ion concentration (e.g., hydrogen or metal ion) in water. The higher concentration of hydrogen ion in solution, the longer reflectance wavelength shifted (from 537 nm to 743 nm). In addition, max-reflectance wavelength is dependent on both metal ion and the concentration. The max reflectance wavelength is shifted from 653 nm (i.e., in water without ion) to 430 nm, 465 nm, and 505 nm for 120 mM of Ca2+, Fe2+, and Cu2+, respectively. Therefore, we can control the photonic band gap of photonic devices by changing the condition of swelling solution. PMID- 26353704 TI - Blue Emitting Materials Based on Naphthylanthracene Derivatives Containing Electron-Withdrawing Fluorobenzenes. AB - We have designed and synthesized three blue emitters based on 9 naphthylanthracene derivatives connected with various electron-withdrawing group such as 4-fluorobenzene, 2,4-difluorobenzene and 2,3,4,5,6-pentafluorobenzene (1 3). Multilayered OLEDs with the structure of ITO (180 nm)/NPB (50 nm)/Blue materials 1-3 (30 nm)/TPBi (15 nm)/Liq (2 nm)/AI (100 nm) have been fabricated to investigate their electroluminescent properties. In particular, the device using 3 showed efficient blue electroluminescent properties with a luminous, power, external quantum efficiency and CIE coordinates of 0.71 cd/A, 1.98 Im/W, 1.34% at 20 mA/cm2 and (x = 0.16, y = 0.20) at 10.0 V, respectively. In addition, a deep blue OLED using 1 with CIE coordinates (x = 0.15, y = 0.11) at 10.0 V exhibited a luminous, power, external quantum efficiency of 2.12 cd/A, 3.04 Im/W and 1.17% at 20 mA/cm2, respectively. PMID- 26353705 TI - Photoelectrochemical Activity of Sodium Titanate Nanobelts for Photoanode. AB - We report photoelectrochemical characteristics of sodium titanate nanobelts as a photoanode. Sodium titanate nanobelts were synthesized by hydrothermal process using titanium(IV) tetrabutoxide in a concentrated aqueous NaOH solution. The formation mechanism of sodium titanate nanobelts in the synthetic process has been comparatively studied on the control of reaction time, pH and concentration of precursors, etc. The morphology and optical property have been investigated with X-ray diffraction, scanning electron microscope, transmission electron microscope, and ultraviolet-visible spectroscopy. On the basis of their morphological and optical characteristics, sodium titanate nanobelts were applied for photoelectrochemical cell as working electrode. After transparent film of sodium titanate nanobelts is formed on the fluorine-doped tin oxide (FTO) glass by doctor blade technique, the photoelectrochemical results were discussed on the structure of photoanode of dye sensitized solar cells. PMID- 26353706 TI - Dermal Toxicity of Flake-Like alpha-Alumina Pigments. AB - Aluminum is one of the most widely used nonferrous metals and an important industrial material, especially for automotive coatings. However, potential toxicity caused by aluminum in humans limits the used of this metal. alpha alumina is the most stable form of aluminum in various phases. Although the results of studies evaluating the dermal toxicity of alpha-alumina remained unclear, this compound can still be used as a pigment in cosmetics for humans. In the current study, we further evaluated the dermal cytotoxic effects of alpha alumina on human skin cells and an in vivo mouse model. We also measured the in vitro penetration profile of flake-like alpha-alumina in porcine skin and assessed the degree of cellular metabolic disorders. Our findings demonstrated that treatment with flake-like alpha-alumina did not significantly affect cell viability up to 24 h. This compound was found to have a non-penetration profile based on a Franz modified diffusion cell assay. In addition, flake-like alpha alumina was not found to induce dermal inflammation as assessed by histology of epidermal architecture, hyperplasia, and the expression of Interleukin-1beta and Cyclooxygenase-2. Results of the cellular metabolic disorder assay indicated that flake-like alpha-alumina does not exert a direct effect on human skin cells. Taken together, our findings provided not only evidence that flake-like alpha alumina may serve as a pearlescent pigment in cosmetics but also experimental basis utilizing alpha-alumina for human application. Our results also obviously provide new insight of the further toxicity study to aluminum based nanoparticles for skin. PMID- 26353707 TI - Exclusive-OR Encryption by Photoconduction and Two-Photon Absorption in Carbon Nanotubes. AB - A two-wave photoconductive system dependent on the nonlinear optical absorption in carbon nano-tubes is presented. Optical irradiation at 532 nm wavelength and 1 nanosecond pulse duration was employed for performing the experiments. A vectorial two-wave mixing configuration was used in order to measure the absorptive and refractive nonlinearities. A single-beam transmittance technique was carried out to evaluate the photoconductivity and also it allows us to confirm the participation of the nonlinear optical absorption displayed by the samples. A two-photon absorption effect was identified as the main physical mechanism associated to the third order absorptive nonlinearity. The exclusive disjunctive logic function was achieved by the optoelectronic response of an interferometric configuration. An ultrasonic spray pyrolysis processing route was utilized for the preparation of the samples. The morphology of the nanotubes was estimated by using scanning electronic microscopy. By combining the photoconductive response of two different carbon nanotubes thin film samples, a straightforward XOR encryption was performed. PMID- 26353708 TI - Preparation and Thermo-Physical Properties of Fe2O3-Propylene Glycol Nanofluids. AB - Iron oxide (Fe2O3) nanoparticles were prepared from ferric chloride and ferrous sulphate by precipitation reaction. Fe2O3-propylene glycol nanofluid was prepared by dispersing Fe2O3 nanoparticles in propylene glycol through stirred bead milling, shear homogenization and probe ultrasonication. The nanofluid was characterized through measurement of viscosity, particle size distribution and thermal conductivity. The interactions between Fe2O3 nanoparticles and propylene glycol on the nanoparticle surfaces lead to reduction in viscosity, the magnitude of which increases with nanoparticle concentration (0-2 vol%) at room temperature. The thermal conductivity enhancement for 2 vol% nanofluid was about 21% at room temperature, with liquid layering being the major contributor for thermal conductivity enhancement. PMID- 26353709 TI - Mechanical Properties of Crystalline Silicon Carbide Nanowires. AB - In this paper, the mechanical properties of crystalline silicon carbide nanowires, synthesized with a catalyst-free chemical vapor deposition method, were characterized with nanoscale tensile testing and mechanical resonance testing methods inside a scanning electron microscope. Tensile testing of individual silicon carbide nanowire was performed to determine the tensile properties of the material including the tensile strength, failure strain and Young's modulus. The silicon carbide nanowires were also excited to mechanical resonance in the scanning electron microscope vacuum chamber using mechanical excitation and electrical excitation methods, and the corresponding resonance frequencies were used to determine the Young's modulus of the material according to the simple beam theory. The Young's modulus values from tensile tests were in good agreement with the ones obtained from the mechanical resonance tests. PMID- 26353710 TI - Carbon Nanotube Sheet as Top Contact Electrode for Nanowires: Highly Versatile and Simple Process. AB - In the past years, lots of research works were dedicated to nanowires and their integration into functional devices. However, despite the great potential of such materials, no device based on nanowires has been transferred in all-day-life. In fact, the vertical device integration is slowed down by the difficulty to contact easily the top electrode. With this work, we present a simple, elegant and versatile process for creating a top electrode contact on nanowires: a carbon nanotube sheet is suspended at the top of the nanowire field. The proof of concept is made through the realization of photovoltaic devices composed of an assembly of vertical PN-junctions based on silicon nanowires. For an illumination density of 100 mW . cm-2, our devices exhibit short circuit current density as high as 15 mA . cm-2. Due to the numerous advantages of the carbon nanotube sheets as top electrode, such as transparency, porosity, good mechanical performance and no need to embed nanowires, such simple and elegant technology should definitely find developments in every field of nanotechnology. PMID- 26353711 TI - Biosynthesis of Gold Nanoparticles Using Novel Bamboo (Bambusa chungii) Leaf Extracts. AB - Gold nanoparticles (Au NPs) have drawn significant interest because of their antisotropic physical properties in biomedical applications. In this paper, we reported the application of bamboo (Bambusa chung) leaf extracts, previously not exploited, in the synthesis of Au NPs at ambient temperature. The average dimension of quasi-spherical Au NPs was 28.8+/-4.5 nm by transmission electron microscopy (TEM). The UV-vis spectroscopy gave an optimal reaction time of 180 min in the process of bioreduction. The organic shell of Au NPs was characterized by Fourier transform infrared (FTIR) spectra and thermogravimetric analysis (TGA), suggesting that the main compositions of the organic shell were hydroxyflavones. The X-ray diffraction (XRD) studies indicated the Au NPs were (111) oriented. This eco-friendly method for the synthesis of Au NPs was simple, amenable for large scale commercial production and biological applications to future in vivo imaging and cancer therapy. PMID- 26353712 TI - A Study on the Rectification Property of Self-Assembled Viologen Single Molecules Using a Scanning Tunneling Microscopy. AB - An ultrahigh vacuum scanning tunneling microscopy (UHV-STM) and a scanning tunneling spectroscopy (STS) are used measure the rectification property of self assembled viologen single molecules (VC8SH, VC10SH, HSC8VC8SH, and HSC10VC10SH) in the previous study. Using STM we observe viologen single molecules in the self assembled octanethiol (OT) SAM matrix. In the OT matrix a mixed phase that includes a c(4 x 2) superlattice of high-density standing up-phase is observed. We indicate high peak current-like rectifications at + 1.68 V(VC8SH), + 1.56 V(VC10SH), + 1.14 V(HSC8VC8SH), and + 1.04 V(HSC10VC10SH) based on the experiment implemented in this study. In addition, transition voltages (Vtrans) from direct tunneling to the Fowler-Nordheim tunneling are presented at 1.08 V(VC8SH), 0.97 V(VC10SH), 0.99 V(HSC8VC8SH), and 0.89 V(HSC1VC1SH). PMID- 26353713 TI - Enhanced Performance in Bulk Heterojunction Polymer Solar Cell Using Water Soluble Conjugated Polymer. AB - We have synthesized water-soluble polymer, poly[(9,9-bis((6'-(N,N,N trimethylammonium)hexyl)-2,7-fluorene))-alt-bisphenylfumaronitrile]dibromide (AHF alt-PFN), the polymer typically obtained by the Suzuki type of polymerization reaction and shows good solubility in methanol. Bulk heterojunction polymer solar cells (BHJ-PSCs) fabricated by using water soluble conjugated polymer and positive (Cs+) and negative (F-, CO2-(3)) charge ions doping as an interfacial layer for poly(3-hexylthiophene):phenyl-C61 butyric acid methyl ester (P3HT:PCBM). We have achieved an enhancement of the short circuit density and power conversion efficiency in solar cell by introducing poly(AHF-alt-PFN) layer between the active layer and the cathode metal. The device with poly(AHF-alt-PRN) layer containing F-, CO2-(3) showed a short circuit current density more 1.3, 2.3 times higher than those of the device without poly(AHF-alt-PFN) + ion layer. We explain the better performance in solar cell with poly(AHF-alt-PFN) + ion layer was due not only to the increase of electron mobility in poly(AHF-alt-PFN) layer but also to the decrease of the electron barrier near cathode by the addition of the negative ions. PMID- 26353714 TI - Ethylene Vinyl Alcohol Nanocomposite Films: Comparison of Their Properties at Various Equibiaxial Stretching Ratios. AB - Ethylene vinyl alcohol (EVOH) hybrid films containing 3 wt% Cloisite 10A were stretched equibiaxially at various stretching ratios in the range 100-200% to investigate the thermo-optical properties and oxygen permeabilities of the films in detail. The effects that variations in the equibiaxial stretching ratio had on clay dispersion and morphology were also determined. The optical transparency and oxygen barrier property were almost constant irrespective of the increase in the stretching ratio from 125 to 200%. PMID- 26353715 TI - Effect of Substrate Temperature on Ti/TiO2 Layers Growth Using a Combined Sputtering/Sol-Gel Combustion Method. AB - A combined radio frequency sputtering/sol-gel combustion method was investigated in order to obtain optimum process condition for fabrication of a Titanium (Ti)/Titanium oxide (TiO2) films electrode of transparent conductive oxide-less dye-sensitized solar cells (TCO-less DSCs), Experimentally, the substrate temperature was changed from R.T. to 500 degrees C, and it was found that there existed an optimum value for efficient performance of the cell. The porous Ti layer with low sheet resistance (-2.5 Omega/sq.) can be prepared by substrate temperature 250 degrees C under RF power 300 W and Ar 8 mTorr. The efficiency (eta) of the cell was 6.52% [FF: 0.76, VOC: 0.72 V, JSC: 11.91 mA/cm2]. PMID- 26353716 TI - Copper Ferrocyanide-Functionalized Magnetic Nanoparticles for the Selective Removal of Radioactive Cesium. AB - Copper ferrocyanide-functionalized magnetite nanoparticles (Cu-FC-MNPs) were successfully synthesized by immobilizing copper and ferrocyanide on the surfaces of [1-(2 amino-ethyl)-3-aminopropyl] trimethoxysilane-modified magnetite nanoparticles. Radioactive cesium (Cs) adsorption tests were conducted to investigate the effectiveness of the Cu-FC-MNPS toward the removal of radioactive Cs. The Cu-FC-MNPs showed excellent separation properties using an external magnet in an aqueous solution. PMID- 26353717 TI - Electricity Generation from Microbial Fuel Cell with Polypyrrole-Coated Carbon Nanofiber Composite. AB - Polyacrylonitrile (PAN) nanofibers, with and without embedded carbon nanotubes (CNTs) were fabricated by the electrospinning process. Polypyrrole (PPy) was coated on the activated PAN/CNT nanofiber by in-situ chemical polymerization in order to improve the electrochemical performance. The electrocatalytic behaviors of the PPy-PAN/CNT composite anode were investigated by means of cyclic voltammetry to evaluate as the anode for microbial fuel cells (MFCs) application. In comparison with unmodified carbon cloth (CC) anodes, PPy-PAN/CNT nanofiber composite showed the improvement of the maximum power density by 40%. The PPy PAN/CNT nanofiber composite electrode therefore offers good prospects for application in MFCs. PMID- 26353718 TI - Tunable Fabrication and Optical Properties of Metal Nano Hole Arrays. AB - Large area polystyrene sphere (PS) arrays with different diameters were prepared by an interface self-assembly method. The inter-particle spacing of PSs was reduced by O2-plasma treatment. When O2-plasma treatment time was long enough, the space of PS arrays could be relatively large. After deposition of Au film and removing the PS masks, we obtained the Au holes arrays instead of Au triangle arrays as normal. The period and the diameter of the hole arrays can be adjusted by the PS with different size and by the O2-plasma treatment time. Then their optical property can be tuned effectively due to the surface plasmon resonance on these structures. PMID- 26353719 TI - Synthesis and Evaluation of DNA Based Quantum Dot Fluorescence In Situ Hybridization (FISH) Probe for Telomere Detection. AB - Efficient oligonucleotide probe design and synthesis based on polymer-coated CdSe/ZnS quantum dot (QD) is demonstrated for detection of telomeres in human monocyte and Leishmania major, a protozoan pathogenic parasite. The highly photoluminescent polymer-coated QDs conjugated with various length of telomere probe sequences were prepared via carbodiimide chemistry and characterized. Specific detection of telomere was observed when DNA sequence was (CCCAAT)n (n = 5 or 3) probe sequence, rather than (GGGTTA)n (n = 3, 5, 8). The sensitivity and specificity were comparable with commercially available PNA probe for human telomere detection. PMID- 26353720 TI - Highly Dispersed Gold Nanoparticles Supported on SBA-15 for Vapor Phase Aerobic Oxidation of Benzyl Alcohol. AB - Gold nanoparticles supported on SBA-15 are prepared by homogenous deposition precipitation method (HDP) using urea as the precipitating agent. The structural features of the synthesized catalysts were characterized by various techniques such as X-ray diffraction (XRD), transmission electron microscopy (TEM), nitrogen adsorption-desorption (BET), pore size distribution (PSD), CO chemisorption and X ray photoelectron spectroscopy (XPS). The catalytic activity and stability of the Au/SBA-15 catalysts are investigated during the vapor phase aerobic oxidation of benzyl alcohol. The BJH pore size distribution results of SBA-15 support and Au/SBA-15 catalysts reveals that the formation of mesoporous structure in all the samples. TEM results suggest that Au nanoparticles are highly dispersed over SBA 15 and long range order of hexagonal mesopores of SBA-15 is well retained even after the deposition of Au metallic nanoparticles. XPS study reveals the formation of Au (0) after chemical reduction by NaBH4. The particle size measured from CO-chemisorption and TEM analysis are well correlated with the TOF values of the reaction. Au/SBA-1 5 catalysts are found to show higher activity compare to Au/TiO2 and Au/MgO catalysts during the vapor phase oxidation of benzyl alcohol. The catalytic functionality are well substantiated with particle size measured from TEM. The crystallite size of Au in both fresh and spent catalysts were measured from X-ray diffraction. PMID- 26353721 TI - Highly Ordered Porous Anodic Alumina with Large Diameter Pores Fabricated by an Improved Two-Step Anodization Approach. AB - The aim of this study is to prepare highly ordered porous anodic alumina (PAA) with large pore sizes (> 200 nm) by an improved two-step anodization approach which combines the first hard anodization in oxalic acid-water-ethanol system and second mild anodization in phosphoric acid-water-ethanol system. The surface morphology and elemental composition of PAA are characterized by field emission scanning electron microscopy (FESEM) and energy-dispersive X-ray spectrometer (EDS). The effects of matching of two-step anodizing voltages on the regularity of pore arrangement is evaluated and discussed. Moreover, the pore formation mechanism is also discussed. The results show that the nanopore arrays on all the PAA samples are in a highly regular arrangement and the pore size is adjustable in the range of 200-300 nm. EDS analysis suggests that the main elements of the as-prepared PAA are oxygen, aluminum and a small amount of phosphorus. Furthermore, the voltage in the first anodization must match well with that in the second anodization, which has significant influence on the PAA regularity. The addition of ethanol to the electrolytes effectively accelerates the diffusion of the heat that evolves from the sample, and decreases the steady current to keep the steady growth of PAA film. The improved two-step anodization approach in this study breaks through the restriction of small pore size in oxalic acid and overcomes the drawbacks of irregular pore morphology in phosphoric acid, and is an efficient way to fabricate large diameter ordered PAA. PMID- 26353722 TI - Synthesis of Hollow beta-Phase GeO2 Nanoparticles. AB - We fabricated mono-dispersed hollow waxberry shaped beta-quartz GeO2 by a facile one-step synthesis in emulsion at room temperature. TEM images indicated that hollow waxberry shaped GeO2 were consisted of nano-sphere whose average size were estimated to be 20 nm. The growth mechanism and optical properties of the products were also investigated. It was found that addition of n-butanol and PVP were crucial factors to control the morphology of GeO2. The possible formation mechanism of the hollow interior is proposed as the Ostwald ripening. The optical properties of the beta-GeO2 nanoparticles with hollow shapes were also studied with photoluminescence spectrum, which reveals a broad emission, suggesting potential applications in electronic and optoelectronic nanodevices. These attractive results provide us a new simple method further used to fabricate other specific hollow structure and indicate hollow waxberry shaped GeO2 may have potential applications in light-emitting nanodevices. PMID- 26353724 TI - Synthesis and Characterization of New Poly(silole-fluorene) Copolymers. AB - New poly(silole-fluorene) copolymers were designed and synthesized. Copolymers were obtained by Suzuki coupling reaction with different ratio of fluorene and silole. The obtained copolymers were characterized by the spectroscopic methods such as FT-IR and 1H-NMR spectroscopies. The resulting copolymers were soluble in common organic solvents such as toluene, tetrahydrofurane, chloroform, chlorobenzene, etc. The obtained copolymers showed thermal stabilities, which were characterized by TGA and DSC. PLEDs with device configurations of ITO/PEDOT:PSS/Copolymer I~VI/LiF/AI. The best device performances, with maximum brightness of 231.5 cd/m2 at a current density (J) of 408.3 mA/cm2, and a maximum luminance efficiency of 0.115 cd/A, were achieved in the composition of fluorene and silole moiety (0.9:0.1). PMID- 26353723 TI - Preparation of Hydrogenase and Viologen-Functionalized Carbon Nanotube Composites for Electrochemical Oxidation of Hydrogen. AB - Bionanocomposites of hydrogenase and viologen-functionalized carbon nanotubes (H2ase/V-MWNTs) were prepared and characterized by using infrared spectra and scanning electron microscope. Cyclic voltammograms revealed two couples of redox waves corresponded to the electron transfer processes of viologens and [4Fe 4S]2+/1+ clusters of hydrogenase. The current intensity was enhanced in the H2 atmosphere, which suggested that the present bio-nanocomposites could be used as heterogeneous bio-catalyst to catalyze reversible reaction between protons and H2. PMID- 26353725 TI - Synthesis and Characterization of Microwave-Exfoliated Graphene Oxide-Wrapped Silicon Nanowire via Hydrosilylation. AB - Single-crystalline silicon nanowires (SiNWs) were fabricated by using an electroless metal-assisted etching of bulk silicon wafers with silver nanoparticles obtained by wet electroless deposition. The etching of SiNWs is based on sequential treatment in aqueous solutions of silver nitrate followed by hydrofluoric acid and hydrogen peroxide. Free-standing SiNWs were then obtained using ultra-sono method in toluene. Graphene oxide was prepared using the modified Hummers' process. Activated microwave-exfoliated graphite oxide (MEGO) was prepared and used for composition of silicon nanowires and graphene oxide via hydrosilylation. The silicon nanowire-graphene composite materials were characterized using XPS and FE-SEM. PMID- 26353726 TI - Changing Electric Resistance of ZnO Nano-Rods by Sulfur Compounds for Chemical Gas Sensor. AB - In this study, a zinc oxide (ZnO) single crystal rod was synthesized for applications as a gas-sensing material for hydrogen sulfide (H2S) and its H2S sensing properties were investigated. H2S absorbed well on ZnO via a gas and solid chemical reaction, resulting in the conversion of ZnO to ZnS. ZnS is also oxidized easily to ZnO with O2 contained in air. ZnO and ZnS are semiconducting materials. The energy band gap of ZnS is higher than that of ZnO. Therefore, the electric conductivity of ZnS must be lower than that of ZnO. On the other hand, different results were obtained in the H2S sensing tests. The energy band gap of sulfur-absorbed ZnO nano-rods was 2.84 eV according to UV-Visible spectrophotometry. The electrical conductivity can be enhanced by sulfur doping on ZnO single crystal rods because the lattice oxygen on the surface of ZnO single crystal is replaced with the sulfur in H2S. The electrical conductivity of S-doped ZnO also decreased due to oxidation with the oxygen in air. PMID- 26353727 TI - Functionalized, Fluorescent, Conjugated Polymer Nanospheres for Protein Targeting via Forster Resonance Energy Transfer. AB - We report the preparation of fluorescent nanospheres based on conjugated polymers, which enables a facile fluorescence color tuning. The fluorescent nanospheres have aldehyde groups on the surface that enable the introduction of a protein ligand, biotin. The intrinsic fluorescence of the nanospheres allows detection of a dye-labeled target protein, streptavidin, via Forster resonance energy transfer. The controlled biofunctionalization of conjugated polymer-based fluorescent nanospheres represents a novel approach with high applicability to sensing of biological molecules. PMID- 26353728 TI - Formation and Characterization of Silver Nanoparticle Composite with Poly(p-Br/F phenylsilane). AB - The one-pot production and structural characterization of composites of silver nanoparticles with poly(p-Br/F-phenylsilane), Br/F-PPS, have been performed. The conversion of Ag+ ions to stable Ag0 nanoparticles is mediated by the copolymer Br/F-PPS having both possibly reactive Si-H bonds in the polymer backbone and C Br bonds in the substituents along with relatively inert C-F bonds. Transmission electron microscopy and field emission scanning electron microscopy analyses show the formation of the composites where silver nanoparticles (less than 30 nm of size) are well dispersed over the Br/F-PPS matrix. X-ray diffraction patterns are consistent with that for face-centered-cubic typed silver. The polymer solubility in toluene implys that the cleavage of C-Br bond and the Si-F dative bonding may not be occurred appreciably at ambient temperature. Nonetheless, thermogravimetric analysis data suggest that some sort of cross-linking could take place at high temperature. Most of the silver particles undergo macroscopic aggregation without Br/F-PPS, which indicates that the polysilane is necessary for stabilizing the silver nanoparticles. PMID- 26353729 TI - Enhanced Acid Diffusion Control by Using Photoacid Generator Bound Polymer Resist. AB - Photoacid generators (PAGs) have been widely used as a key component for improving photoresist performance. The acid diffusion influences on the photoresist characteristics of resolution and line edge roughness (LER). The PAG bound polymer resist has been a key component for solving the problems of PAG aggregation and acid diffusion control. A triphenyl sulfonium salt methacrylate as PAG was synthesized and copolymerized with crosslinkable glycidyl methacrylate and methyl methacrylate by radical reaction for a new PAG bound polymer resist. The characterization of resist polymers was carried out by 1H NMR. The lithographic performance of photoresists was investigated by ArF lithography. Both PAG bound resist and the PAG blended resist were employed to demonstrate the effect of PAG unit in a resist system. The polymer bound PAG resist improved the LER and showed a higher resolution than the PAG blend resist. PMID- 26353731 TI - Reductant Control on Particle Size, Size Distribution and Morphology in the Process of Surface Enhanced Raman Spectroscopy Active Silver Colloid Synthesis. AB - The present study demonstrates how reducing agents play an important role in synthesis of silver nanoparticles (AgNPs) in colloidal phase. It is apparent from the observed results that borohydride, one of the most widely used reductants, induces reduction leading to the formation of spherical particles with narrowest size distribution. In contrast, ascorbic or citrate mediated reduction leads to formation of anisotropic silver nanoparticles, indicating the role of anionic carboxylate in template driving process. In view of recent green chemistry approach for synthesizing silver nanoparticles involving glucose as reductant and starch as capping groups, we have followed in detail the dependence of glucose induced reduction process on different synthesis parameters, such as concentration, temperature and time of reactions. The phase of the synthesized particles was found to be face centred cubic (fcc), which was independent of the reductants employed. Further, we have endeavored to look into the Surface enhanced Raman spectroscopy (SERS) of crystal violet and rhodamine 6G in the presence of AgNPs substrate synthesized by using the reducing agents in question without involving any other structural modulating additive, such as ionic salt, etc. Here, the observed results provide a guideline on the selection of reducing agents and appropriate conditions for application specific synthesis of silver nanoparticles. PMID- 26353730 TI - Immobilization of Antibody on a Cyclic Olefin Copolymer Surface with Functionalizable, Non-Biofouling Poly[Oligo(Ethylene Glycol) Methacrylate]. AB - We report a perfluoroaryl azide-based photoreaction for synthesizing functionalizable and nonbiofouling poly[oligo(ethylene glycol) methacrylate] (pOEGMA) films on a chemically inert COC substrate, and an estimation of a surface coverage of the antibody immobilized onto the surface with the immuno gold nanoparticles. The processes were confirmed by water contact angle measurement, FT-IR spectroscopy, and FE-SEM. The strategy demonstrated in this work could be applied to functionalizations of other polymeric materials and determination of the binding capacity of analytes in biosensors and microfluidic devices. PMID- 26353732 TI - Preparation, Characterization of High-Luminescent and Magnetic Eu3+, Dy3+ Doped Superparamagnetic Nano-Fe3O4. AB - Pure superparamagnetic nano-Fe3O4 (SPMNPs) and Ln3+ (Eu3+, Dy3+) doped SPMNPs are successfully synthesized by reverse micelle method. The structure, morphology, magnetic properties and PL properties of the samples were characterized by XRD, FT-IR, TEM, PPMS, EDS and luminescence spectrometer respectively. The influences of Ln3+ doping amount on magnetic properties and PL properties were investigated in detail. The results show, with increasing of the Lna+ doping amount increasing, the morphologies and particle sizes of the doped Fe304 nanoparticles change, leading to saturation magnetization and coercivity changing accordingly. The change of lattice parameter and particle size was discussed based on Rietveld analysis of XRD pattern of the doped Fe3O4 nanoparticles. The coincidence of the ZFC and FC magnetization curves within the temperature range from 120.6 to 300 K, indicating that Fe3O4 nanoparticles are single domain super-paramagnetic. PMID- 26353733 TI - Correlation Analysis Between Expression Levels of Hepatic Growth Hormone Receptor, Janus Kinase 2, Insulin-Like Growth Factor-I Genes and Dwarfism Phenotype in Bama Minipig. AB - Animal growth and development are complex and sophisticated biological metabolic processes, in which genes plays an important role. In this paper, we employed real-time quantitative PCR (RT-qPCR) to analyze the expression levels of hepatic GHR, JAK2 and IGF-I genes in 1, 30, 180 day of Bama minipig and Landrace with attempt to verify the correlation between the expression of these growth associated genes and the dwarfism phenotype of Bama minipig. The results showed that the expression levels of these 3 genes in Bama minipigs were down-regulated expressed from 1 day to 30 day, and which was up-regulated expressed in Landrace. The expression levels of the 3 genes on 1, 30, 180 day were prominently higher in Landrace than in Bama minipigs. The significant differences of the 3 genes expression levels on 1 day between this two breeds indicate that different expressions of these genes might occur before birth. It is speculated that the down-regulated expression of the 3 genes may have a close correlation with the dwarfism phenotype of Bama minipig. More investigations in depth of this study is under progress with the help of biochip nanotechnology. PMID- 26353734 TI - Factorial Design and Development of Solid Lipid Nanoparticles (SLN) for Gene Delivery. AB - Several scientific hurdles still have to be overcome before gene therapy becomes a reality. One of them is the development of safe and efficient gene delivery system. Here, we have employed factorial design to optimize the production of solid lipid nanoparticles (SLN) for gene delivery. A 2 x 3 full-factorial experimental design was used for the optimization of SLNs formulations. The variables were defined by the components of the formulation: concentration of stearic acid, DOTAP, and Pluronic F68 at two levels (-1, 1) and 3 central points (0). Different SNL formulations were prepared by varying the amount of components and several properties were tested, including their capacity to accommodate DNA and protection against DNase degradation, colloidal stability, in vitro cytotoxicity, and transfection efficiency in prostate cancer cells. Finally, response Surface Methodology was used to select the most effective formulation for gene delivery to prostate cancer cells in vitro. In conclusion, this study revealed that stearic acid and Pluronic F68 were determinant to SLN size and stability, respectively, while small amounts of DOTAP are essential for a successful transfection. PMID- 26353735 TI - Multi-Walled Carbon Nanotube Growth in Multi-Walled Carbon Nanotubes by Chemical Vapor Deposition. AB - We report chemical vapor deposition (CVD) growth of a multi-walled carbon nanotube (MWCNT) inside another MWCNTs from a cementite (Fe3C) catalyst nanoparticles. The CNTs have bi or tri-layered core(s)-sheath structure with various crystallinity. The sheath grows first at a lower temperature, and then the catalyst nanoparticle works again to grow the core(s) at a higher temperature in the tip or root growth mode. Transmission electron microscopy (TEM) observation provides a clear piece of evidence of reverse-inward growth. PMID- 26353736 TI - Localized Surface Plasmon Resonance in Au Nanoparticles Embedded dc Sputtered ZnO Thin Films. AB - The plasmonic behavior of metallic nanoparticles is explicitly dependent on their shape, size and the surrounding dielectric space. This study encompasses the influence of ZnO matrix, morphology of Au nanoparticles (AuNPs) and their organization on the optical behavior of ZnO/AuNPs-ZnO/ZnO/GP structures (GP: glass plate). These structures have been grown by a multiple-step physical process, which includes dc sputtering, thermal evaporation and thermal annealing. Different analytical techniques such as scanning electron microscopy, glancing angle X-ray diffraction, Rutherford backscattering spectrometry and optical absorption have been used to study the structures. In-situ rapid thermal treatment during dc sputtering of ZnO film has been found to induce subtle changes in the morphology of AuNPs, thereby altering the profile of the plasmon band in the absorption spectra. The results have been contrasted with a recent study on the spectral response of dc magnetron sputtered ZnO films embedded with AuNPs. Initial simulation results indicate that AuNPs-ZnO/Au/GP structure reflects/absorbs UV and infrared radiations, and therefore can serve as window coatings. PMID- 26353737 TI - The Effect of Local Electric Field in the Middle Dielectric Wall on the Infrared Plasmonic Shift of the Concentric Gold Double Nanotubes. AB - The effect of inserted gold nanotube on the localized surface plasmon resonance (LSPR) shifting and local electric field enhancement of concentric gold double nanotubes has been studied by using the quasi-static electricity. Because of the combined effect from inter-surface and inter-tube plasmon coupling, the LSPR in gold double nanotubes could be easily tuned into the infrared wavelength region. The calculation results indicate the plasmon peak shifting is quite sensitive to the thickness of the inner gold tube and the gap between the inner and outer gold tubes. The physical mechanism has been attributed to the local field effect of the separate dielectric layer. Because of the additional attraction from the inner gold tube to the free electrons at outer gold tube, the decreasing electric field in the middle dielectric spacer layer reduces the restoring force and lead to intense red shift of LSPR. PMID- 26353738 TI - Single-Walled Carbon Nanohorns Inhibit Proliferation of Conjunctival Melanoma Cell Lines CRMM-1 and Involved in Energy Metabolism. AB - SWNHs induces accumulate with the levels of cytotoxic effects on different cell types and organs in animal models; it in a wide range may used for biomedical imaging. Conjunctival melanoma is a rare but potentially fatal ocular surface tumor. Recent studies of us have indicated the ability of SWNHs to inhibit proliferation of conjunctival melanoma cell line CRMM-1. But the role and molecular mechanisms of it was unclear. To address this question, the research about direct role of SWNHs on the growth, proliferation and apoptosis of CRMM-1 had been performed. Our results indicate that followed with the increasing concentrations of SWNHs, the number of cells decreased and apoptotic cells increased significantly. SWNHs delayed obviously mitotic entry of cells, and these effects followed the cultured time and the gradually increasing concentrations of SWNHs. SWNHs inhibited proliferation of cells at each time point in a time and dose-dependent manner, too. The TEM images showed that individual spherical SWNHs particles smaller than 100 nm in diameters were localized inside cytoplasma of cells. In summary, SWNHs inhibited mitotic entry, growth and proliferation of conjunctival melanoma cells and promoted its apoptosis, inhibited energy metabolism of cells in a dose-dependent manner. The roles of SWNHS on conjunctival melanoma cells were implicating energy metabolism. It may be the effective methods for treatment to conjunctival melanoma. PMID- 26353739 TI - Self-Emulsifying Drug Delivery System for Enhancing Bioavailability and Lymphatic Delivery of Tacrolimus. AB - A self-emulsifying drug delivery system (SEDDS) containing tacrolimus has been developed to enhance the bioavailability and lymphatic delivery of tacrolimus. Solubility tests, combination tests, and phase diagrams were constructed for different sorts and ratios of oils, surfactants, and cosurfactants to identify optimal formulation. Optimized SEDDS was assessed for droplet size, zeta potential, stability in various media, and in vitro release. The tacrolimus loaded SEDDS and commercial capsule (Prograf(r)) were orally administered (5 mg/kg) to rats. Whole blood, and mesenteric and axillary lymph node samples were taken and the concentrations of tacrolimus were measured to evaluate pharmacokinetic characteristics and the lymphatic delivery effects. The optimized SEDDS droplets were approximately 40 nm in size and stable enough to endure gastric pH environments. The release rate of tacrolimus from SEDDS was significantly higher than that from the commercial capsule. The bioavailability of tacrolimus in SEDDS after oral administration was significantly improved versus that of Prograf(r). The lymphatic targeting efficiency of the prepared SEDDS formulation showed significantly greater than that of Prograf(r). Our research indicates that prepared SEDDS can be an alternative to the conventional oral formulation of tacrolimus. Furthermore, SEDDS should be explored as a potential drug carrier for other lipophilic drugs. PMID- 26353740 TI - Synthesis and Properties of an Ionic Conjugated Polymer via the Uncatalyzed Polymerization of 2-Ethynylpyridine Using Bromocholine Bromide. AB - A new ionic polyacetylene was synthesized via the uncatalyzed polymerization of 2 ethynylpyridine using bromocholine bromide in high yield. The activated acetylenic triple bond of N-bromocholine-2-ethynylpyridinium bromide, formed at first quaternarization process, was found to be susceptible to linear polymerization. The polymer structure was characterized by various instrumental methods to have the polyacetylene backbone structure with the designed substituent. The inherent viscosities of the resulting polymers were in the range of 0.10-0.15 dL/g and X-ray diffraction analysis data indicated that this polymer is mostly amorphous. The electro-optical and electrochemical properties were measured and discussed. The polymer exhibited the irreversible electrochemical behaviors between the doping and undoping peaks. PMID- 26353741 TI - Characteristics and Durability of Vertical-Type Organic Light-Emitting Transistors Using Poly(2-methoxy-5-(2- ethyl hexyloxy)-1,4-phenylenevinylene) and Indenofluorenedione Derivatives. AB - In this study, we have fabricated vertical organic light emitting transistors using indenofluorenedione derivatives (IF-dione-F) as an n-type organic semiconductor. IF-dione-F shows high performance n-type semiconductors owing to the fluorine group in the IF-dione-F backbone. The fluorine group has an electron withdrawing property. Thus, IF-dione-F shows high electron affinity and good durability. The configuration of the vertical organic light emitting transistors was ITO (drain)/ PEDOT: PSS/MEH-PPV/IF-dione-F/AI (gate)/IF-dione-F/Al (source). The characteristics of the vertical organic light emitting transistors were investigated from the measurements of radiancevoltage characteristics and external quantum efficiency. Furthermore, air stability was studied from the measurements of characteristics, impedance spectroscopy and contact angle. PMID- 26353742 TI - New Approach Way Using Substituent Group at Core Chromophore for Solution Process Blue Emitter. AB - Comparing the conventional vapor desposition process for OLEDs, the solution process using small molecules has merits of low production cost because of many reasons. For the solution process blue flourescent material, tertiary butyl (T) and anthracene (A) were first introduced as substituents to TAT core part, 2-tert butyl-9,10-bis(3",5"-diphenylbiphenyl-4'-yl)anthracene (T-TAT) and 2-(9 anthracenyl)-9,10-bis(3",5"-diphenylbiphenyl-4'-yl)anthracene (A-TAT). All three materials indicated typical absorption band of anthracene in the range of 350 to 400 nm. T-TAT exhibited similar optical properties to TAT, but A-TAT has longer absorption and PL emission compared to other two compounds. In case of spin coated film, A-TAT exhibited absorption maximum value of 408 nm and photoluminescence maximum value of 469 nm. T-TAT and A-TAT can be applicable to solution process as a blue fluorescence material. PMID- 26353743 TI - Effects of Ce Ion-Modification on an Open Circuit Photovoltage Properties of ZnO Nanowires-Based Dye-Sensitized Solar Cell. AB - We investigated the photoelectrochemical effects on Ce ion-modified ZnO nanowires for dye-sensitized solar cells (DSSCs), preparing four kinds of samples grown in solutions with 0, 1, 2, and 3 atomic percent (at%) of Ce precursors. It was found that Ce ion modifications lead to an increase in the lattice constant of ZnO nanowires, resulting in widening of their PL visible band and UV blueshift. I-V results tell that the photoelectrochemical properties increase in the order of 1, 2, 0, and 3 at% Ce ion-modified ZnO nanowire-based DSSCs. To further analyze and explain the experimental results, we measured absorbance, incident to photon-to current efficiency (IPCE), and concluded that the DSSCs fabricated by using 3 at% Ce ion-modified ZnO nanowires exhibit the best device performances due to large VOC enhancements, suggesting that Ce ion modification leads to the VOC, changes of DSSCs, which can be explained by Burstein-Moss effect. PMID- 26353744 TI - Studies on the Properties of Organic Photovoltaic Cells Using TiOx and DMDCNQI as Double Buffer Layers. AB - Various types of n-type buffer layers have been used in organic electronic devices. These buffer layers turned out to expedite carrier injection and reduce series resistance, leading to good performance of organic electronic devices. In our current work, we have fabricated organic photovoltaic (OPV) cells consisting of ITO/PEDOT:PSS/P3HT:PCBM/TiOx/DMDCNQI/AI which were fabricated in the presence of air. To incorporate the individual advantages of each n-type buffer layer, a DMDCNQI and TiOx layers were inserted to act as n-type double buffer layers. This leads to an increase of short-circuit current (JSC) and fill factor (FF) with good stability, in comparison to P3HT:PCBM based conventional cells. The results imply that the structures of double buffer layers can provide possible alternative to achieving high performance and air durability. PMID- 26353745 TI - Fluorogens with Aggregation Induced Emission: Ideal Photoacoustic Contrast Reagents Due to Intramolecular Rotation. AB - Exogenous contrast agents with high sensitivity are highly desirable for photoacoustic (PA) imaging. In this work, we show that fluorogens with aggregation induced emission (AIE) characteristics are born with strong PA signals. In addition, we find that the PA signal of conventional fluorophores could be significantly enhanced through conjugation with tetraphenylethene (TPE), an iconic AIE fluorogen. Taking 2,3-bis[4-(diphenylamino)phenyl]fumaronitrile (TPAFN) as an example, conjugation between TPAFN and TPE affords 2,3-bis(4 (phenyl(4-(1,2,2-triphenylvinyl)phenyl)amino)phenyl) fumaroni-trile (TPETPAFN), a molecule with significant AIE characteristics, which shows 170% higher PA signals as compared to that of TPAFN. The higher PA signal of TPETPAFN is mainly ascribed to the enhanced molecular rotation, which is beneficial to its thermal expansion upon light absorption. Moreover, the significantly reduced PA signals for TPETPAFN in solvents with high viscosity or as nanoparticles further highlight the contribution of molecular rotation on PA signals. PMID- 26353746 TI - WHO STUDY GROUP ON TOBACCO PRODUCT REGULATION. Report on the Scientific Basis of Tobacco Product Regulations: Fifth Report of a WHO Study Group. AB - This report presents the conclusions reached and recommendations made by the members of the WHO Study Group on Tobacco Product Regulation (TobReg) at its seventh meeting, in December 2013, during which it reviewed background papers specially commissioned for the meeting, which dealt, respectively, with the following four themes: Novel tobacco products, including potential reduced exposure products Smokeless tobacco products: research needs and regulatory recommendations Reduced ignition propensity cigarettes: research needs and regulatory recommendations Non-exhaustive priority list of toxic contents and emissions of tobacco products. The Study Group's recommendations in relation to each theme are set out at the end of the section dealing with that theme; its overall recommendations are summarized in Chapter 6. PMID- 26353747 TI - Development and application of a multi-residue method for the determination of 53 pharmaceuticals in water, sediment, and suspended solids using liquid chromatography-tandem mass spectrometry. AB - Comprehensive source and fate studies of pharmaceuticals in the environment require analytical methods able to quantify a wide range of molecules over various therapeutic classes, in aqueous and solid matrices. Considering this need, the development of an analytical method to determine 53 pharmaceuticals in aqueous phase and in solid matrices using a combination of microwave-assisted extraction, solid phase extraction, and liquid chromatography coupled with tandem mass spectrometry is reported. Method was successfully validated regarding linearity, repeatability, and overall protocol recovery. Method detection limits (MDLs) do not exceed 1 ng L(-1) for 40 molecules in aqueous matrices (6 ng L(-1) for the 13 remaining), while subnanogram per gram MDLs were reached for 38 molecules in solid phase (29 ng g(-1) for the 15 remaining). Losses due to preparative steps were assessed for the 32 analytes associated to their labeled homologue, revealing an average loss of 40 % during reconcentration, the most altering step. Presence of analytes in wastewater treatment plant (WWTP) effluent aqueous phase and suspended solids (SS) as well as in river water, SS, and sediments was then investigated on a periurban river located in the suburbs of Bordeaux, France, revealing a major contribution of WWTP effluent to the river contamination. Sorption on river SS exceeded 5 % of total concentration for amitriptyline, fluoxetine, imipramine, ritonavir, sildenafil, and propranolol and appeared to be submitted to a seasonal influence. Sediment contamination was lower than the one of SS, organic carbon content, and sediment fine element proportion was accountable for the highest measured concentrations. PMID- 26353748 TI - Unsupervised Topic Modeling in a Large Free Text Radiology Report Repository. AB - Radiology report narrative contains a large amount of information about the patient's health and the radiologist's interpretation of medical findings. Most of this critical information is entered in free text format, even when structured radiology report templates are used. The radiology report narrative varies in use of terminology and language among different radiologists and organizations. The free text format and the subtlety and variations of natural language hinder the extraction of reusable information from radiology reports for decision support, quality improvement, and biomedical research. Therefore, as the first step to organize and extract the information content in a large multi-institutional free text radiology report repository, we have designed and developed an unsupervised machine learning approach to capture the main concepts in a radiology report repository and partition the reports based on their main foci. In this approach, radiology reports are modeled in a vector space and compared to each other through a cosine similarity measure. This similarity is used to cluster radiology reports and identify the repository's underlying topics. We applied our approach on a repository of 1,899,482 radiology reports from three major healthcare organizations. Our method identified 19 major radiology report topics in the repository and clustered the reports accordingly to these topics. Our results are verified by a domain expert radiologist and successfully explain the repository's primary topics and extract the corresponding reports. The results of our system provide a target-based corpus and framework for information extraction and retrieval systems for radiology reports. PMID- 26353749 TI - Analyzing PACS Usage Patterns by Means of Process Mining: Steps Toward a More Detailed Workflow Analysis in Radiology. AB - In this paper, statistical analysis and techniques from process mining are employed to analyze interaction patterns originating from radiologists reading medical images in a picture archiving and communication system (PACS). Event logs from 1 week of data, corresponding to 567 cases of single-view chest radiographs read by 14 radiologists, were analyzed. Statistical analysis showed that the numbers of commands and command types used by the radiologists per case only have a slightly positive correlation with the time to read a case (0.31 and 0.55, respectively). Further, one way ANOVA showed that the factors time of day, radiologist and specialty were significant for the number of commands per case, whereas radiologist was also significant for the number of command types, but with no significance of any of the factors on time to read. Applying process mining to the event logs of all users showed that a seemingly "simple" examination (single-view chest radiographs) can be associated with a highly complex interaction process. However, repeating the process discovery on each individual radiologist revealed that the initially discovered complex interaction process consists of one group of radiologists with individually well-structured interaction processes and a second smaller group of users with progressively more complex usage patterns. Future research will focus on metrics to describe derived interaction processes in order to investigate if one set of interaction patterns can be considered as more efficient than another set when reading radiological images in a PACS. PMID- 26353750 TI - Patient centered imaging and the dose of radiopharmaceuticals. PMID- 26353751 TI - Development and validation of a patient-tailored dose regime in myocardial perfusion imaging using conventional SPECT. AB - BACKGROUND: The decreasing image quality in heavier patients can be compensated by administration of a patient-specific dose in myocardial perfusion imaging (MPI) using a cadmium zinc telluride-based SPECT camera. Our aim was to determine if the same can be achieved when using a conventional SPECT camera. METHODS: 148 patients underwent SPECT stress MPI using a fixed Tc-99m tetrofosmin tracer dose. Measured photon counts were normalized to administered tracer dose and scan time and were correlated with body weight, body mass index, and mass per length to find the best predicting parameter. From these data, a protocol to provide constant image quality was derived, and subsequently validated in 125 new patients. RESULTS: Body weight was found to be the best predicting parameter for image quality and was used to derive a new dose formula; A admin (MBq) = 223.body weight (kg)(0.65)/T scan (min). The measured photon counts decreased in heavier patients when using a fixed dose (P < .01) but this was no longer observed after applying a body-weight-dependent protocol (P = .20). CONCLUSIONS: Application of a patient-specific protocol resulted in an image quality less depending on patient's weight. The results are most likely independent of the type of SPECT camera used, and, hence, adoption of patient-specific dose and scan time protocols is recommended. PMID- 26353753 TI - Microbial Toxicity of a Type of Carbon Dots to Escherichia coli. AB - Carbon dots (Cdots), as a class of novel photoluminescence nanoprobes, has attracted tremendous interest for its broad application in recent years. Thus, the toxicity and behavior of Cdots in biological systems become important fundamental problems that require significant attention. In this study, Cdots with diameters of 5 nm are produced using mixed-acid treatment. The Cdots exhibit strong yellow fluorescence under UV irradiation and shifted emission peaks as the excitation wavelength is changed. Gram-negative bacteria Escherichia coli (E. coli) are applied as testing model to study the biological effect of Cdots on the cell growth by microcalorimetric, spectroscopic, and microscopic investigation. The introducing of Cdots caused a gradual increase of the maximum heat power (P peak) and the total heat produced (Q total) at low concentrations (0.0-5.00 mg/L). The metabolism rate constant (k) and half inhibitory concentration (IC50) were calculated from the microcalorimetric data. The results indicated that Cdots had a concentration-dependent effect on the growth of E. coli. For confirmation, the growth curves and colony-forming units at different concentration of Cdots were studied. The morphology of E. coli in the absence and presence of Cdots was determined by scanning electron microscopy (SEM). The results of these studies were in agreement well with the analysis explored from microcalorimetry. PMID- 26353752 TI - Flexible origin of hydrocarbon/pheromone precursors in Drosophila melanogaster. AB - In terrestrial insects, cuticular hydrocarbons (CHCs) provide protection from desiccation. Specific CHCs can also act as pheromones, which are important for successful mating. Oenocytes are abdominal cells thought to act as specialized units for CHC biogenesis that consists of long-chain fatty acid (LCFA) synthesis, optional desaturation(s), elongation to very long-chain fatty acids (VLCFAs), and removal of the carboxyl group. By investigating CHC biogenesis in Drosophila melanogaster, we showed that VLCFA synthesis takes place only within the oenocytes. Conversely, several pathways, which may compensate for one another, can feed the oenocyte pool of LCFAs, suggesting that this step is a critical node for regulating CHC synthesis. Importantly, flies deficient in LCFA synthesis sacrificed their triacylglycerol stores while maintaining some CHC production. Moreover, pheromone production was lower in adult flies that emerged from larvae that were fed excess dietary lipids, and their mating success was lower. Further, we showed that pheromone production in the oenocytes depends on lipid metabolism in the fat tissue and that fatty acid transport protein, a bipartite acyl-CoA synthase (ACS)/FA transporter, likely acts through its ACS domain in the oenocyte pathway of CHC biogenesis. Our study highlights the importance of environmental and physiological inputs in regulating LCFA synthesis to eventually control sexual communication in a polyphagous animal. PMID- 26353755 TI - Dysfunctional loop ileostomy after low anterior resection for rectal cancer in the presence of Meckel's diverticulum: a case report. AB - INTRODUCTION: A temporary protective loop ileostomy is a routine procedure to protect the anastomosis in patients who undergo low anterior resection for rectal cancer. The aim of this case report is to present a rare complication caused by Meckel's diverticulum. CASE PRESENTATION: We describe a case of a 71-year-old white man with dysfunctional ileostomy after low anterior resection for rectal cancer due to adhesions and pressing effects of Meckel's diverticulum near the ileostomy site, which led to volvulus of his small intestine and obstruction. As a result he underwent a supplementary operation to resolve this complication by Meckel's diverticulum resection. CONCLUSIONS: During a low anterior resection for rectal cancer and a protective ileostomy procedure the presence of Meckel's diverticulum should not be ignored. Our proposal is the primary resection of Meckel's diverticulum as the best surgical choice; according to the limited international literature on such cases we report a possible alternative to a protective ileostomy by creating a conduit using Meckel's diverticulum as a stoma. PMID- 26353754 TI - S100A16 promotes differentiation and contributes to a less aggressive tumor phenotype in oral squamous cell carcinoma. AB - BACKGROUND: Altered expression of S100A16 has been reported in human cancers, but its biological role in tumorigenesis is not fully understood. This study aimed to investigate the clinical significance and functional role of S100A16 in oral squamous cell carcinoma (OSCC) suppression. METHODS: S100A16 mRNA and/or protein levels were examined by quantitative RT-PCR and immunohistochemistry in whole- and laser microdissected-specimens of normal human oral mucosa (NHOM, n = 65), oral dysplastic lesions (ODL, n = 21), OSCCs (n = 132) and positive cervical nodes (n = 17). S100A16 protein expression in OSCC was examined for correlations with clinicopathological variables and patient survival. S100A16 was over expressed and knocked-down in OSCC-derived (CaLH3 and H357) cells by employing retroviral constructs to investigate its effects on cell proliferation, sphere formation and three dimensional (3D)-organotypic invasive abilities in vitro and tumorigenesis in a mouse xenograft model. RESULTS: Both S100A16 mRNA and protein levels were found to be progressively down-regulated from NHOM to ODL and OSCC. Low S100A16 protein levels in OSCC significantly correlated with reduced 10-year overall survival and poor tumor differentiation. Analysis of two external OSCC microarray datasets showed a positive correlation between the mRNA expression levels of S100A16 and keratinocyte differentiation markers. CaLH3 and H357 cell fractions enriched for differentiated cells either by lack of adherence to collagen IV or FACS sorting for low p75NTR expression expressed significantly higher S100A16 mRNA levels than the subpopulations enriched for less differentiated cells. Corroborating these findings, retroviral mediated S100A16 over-expression and knock-down in CaLH3 and H357 cells led to respective up- and down-regulation of differentiation markers. In vitro functional studies showed significant reduction in cell proliferation, sphere formation and 3D-invasive abilities of CaLH3 and H357 cells upon S100A16 over-expression. These functional effects were associated with concomitant down-regulation of self-renewal (Bmi-1 and Oct 4A) and invasion related (MMP1 and MMP9) molecules. S100A16 over expression also suppressed tumorigenesis of H357 cells in a mouse xenograft model and the resulting tumor xenografts displayed features/expression of increased differentiation and reduced proliferation/self-renewal. CONCLUSIONS: These results indicate that S100A16 is a differentiation promoting protein and might function as a tumor suppressor in OSCC. PMID- 26353757 TI - Smoke-free zones and higher taxes reduce smoking in young people, US study finds. PMID- 26353756 TI - Effect of consuming a grape seed supplement with abundant phenolic compounds on the oxidative status of healthy human volunteers. AB - BACKGROUND: Diverse enzymatic and non-enzymatic antioxidants provide protection against reactive oxygen species in humans and other organisms. The nonenzymatic antioxidants include low molecular mass molecules such as plant-derived phenols. AIM OF STUDY: This study identified the major phenolic compounds of a grape seed extract by HPLC and analyzed the effect of consumption of biscuits enriched with this extract on the urinary oxidative status of healthy subjects by measurement of urine redox potential. METHODS: The major phenolic compounds were characterized in a red grape seed extract separated by HPLC with detection by a photodiode array (PDA), fluorescence (FL) and quadrupole mass spectrometer (MS). A nutritional study in a healthy volunteers group was done. Each volunteer ate eight traditional biscuits with no red grape seed extract supplementation. The second day each volunteer ate eight traditional biscuits supplemented with 0.6% (wt/wt) of grape seed extract. An overnight urine sample was obtained for each treatment. The redox potential was measured at 25 degrees C using a potentiometer in each urine sample. RESULTS: Epicatechin, catechin, procyanidin dimers B1 to B4, and the procyanidin trimer C2 were the major phenolic components in the extract. Epicatechin gallate and procyanidin dimers B1-3-G and B2-3'-G were the major galloylated flavan-3-ols. The forty-six healthy volunteers each shown a reduction of the urine redox potential after the treatment by traditional biscuits supplemented with the grape seed extract. CONCLUSIONS: This simple dietary intervention significantly reduced (33%) the urine redox potential, reflecting an overall increase in antioxidant status. Incorporation of plant derived phenols in the diet may increase anti-oxidative status. PMID- 26353758 TI - Characterization of the Langendorff Perfused Isolated Mouse Heart Model of Global Ischemia-Reperfusion Injury: Impact of Ischemia and Reperfusion Length on Infarct Size and LDH Release. AB - INTRODUCTION: The Langendorff perfused isolated mouse heart model is commonly used to assess the efficacy of cardioprotective therapies, although the duration of ischemia and reperfusion vary considerably between different laboratories. We aimed to provide a thorough characterization of the model with different durations of ischemia and reperfusion by means of 2 different end points-infarct size (IS) using triphenyltetrazolium staining and lactate dehydrogenase (LDH) release. METHODS: C57/BL6 mice hearts were retrograde perfused on a Langendorff apparatus and allocated into 9 groups in a 3 * 3 factorial design-3 ischemic durations (25, 35, and 45 minutes) matched by 3 reperfusion durations (60, 120, and 180 minutes). A protocol of ischemic preconditioning (IPC) was applied to investigate IS and LDH kinetics with different ischemic durations. RESULTS: Infarct size progressively increased with the duration of both ischemia and reperfusion and was found to be independently associated with both determinants. In terms of LDH release kinetics, a peak was observed within the first 10 to 15 minutes of reperfusion and steadily declined thereafter, although a second smaller peak was observed in the 25-minute ischemia group. Only LDH peak release was associated with the ischemia length, with area under the curve (AUC) failing to follow ischemic duration. Interestingly, while IPC reduced IS in all ischemic durations investigated, a significant attenuation of LDH AUC was only observed in the 25-minute index ischemia group. Only a moderately positive correlation was observed between IS and LDH peak (R = .547, P = .006) and AUC (R = .664, P < .001). CONCLUSION: Myocardial IS measured by triphenyltetrazolium staining depends on both the duration of ischemia and the length of the reperfusion period. The LDH assessment may not be the most reliable tool to assess IS and/or to examine cardioprotective effectiveness at various times of ischemia. PMID- 26353759 TI - Discovering New Biology through Sequencing of RNA. AB - Sequencing of RNA (RNA-Seq) was invented approximately 1 decade ago and has since revolutionized biological research. This update provides a brief historic perspective on the development of RNA-Seq and then focuses on the application of RNA-Seq in qualitative and quantitative analyses of transcriptomes. Particular emphasis is given to aspects of data analysis. Since the wet-lab and data analysis aspects of RNA-Seq are still rapidly evolving and novel applications are continuously reported, a printed review will be rapidly outdated and can only serve to provide some examples and general guidelines for planning and conducting RNA-Seq studies. Hence, selected references to frequently update online resources are given. PMID- 26353760 TI - Phosphatidylinositol 3-Phosphate 5-Kinase, FAB1/PIKfyve Kinase Mediates Endosome Maturation to Establish Endosome-Cortical Microtubule Interaction in Arabidopsis. AB - Phosphatidylinositol 3,5-bisphosphate [PtdIns(3,5)P2] is an important lipid in membrane trafficking in animal and yeast systems; however, its role is still largely obscure in plants. Here, we demonstrate that the phosphatidylinositol 3 phosphate 5-kinase, formation of aploid and binucleate cells1 (FAB1)/FYVE finger containing phosphoinositide kinase (PIKfyve), and its product, PtdIns(3,5)P2, are essential for the maturation process of endosomes to mediate cortical microtubule association of endosomes, thereby controlling proper PIN-FORMED protein trafficking in young cortical and stele cells of root. We found that FAB1 predominantly localizes on the Sorting Nexin1 (SNX1)-residing late endosomes, and a loss of FAB1 function causes the release of late endosomal proteins, Ara7, and SNX1 from the endosome membrane, indicating that FAB1, or its product PtdIns(3,5)P2, mediates the maturation process of the late endosomes. We also found that loss of FAB1 function causes the release of endosomes from cortical microtubules and disturbs proper cortical microtubule organization. PMID- 26353762 TI - Validation of a Soft Tissue Sarcoma Nomogram Using a National Cancer Registry. AB - BACKGROUND: A nomogram to predict disease-specific mortality (DSM) following surgery for soft tissue sarcoma (STS) has been developed by the Memorial Sloan Kettering Cancer Center (MSKCC). The goal of this study was to validate this nomogram by assessing discrimination and calibration at the population level using a national cancer database. METHODS: Retrospective review of the Surveillance, Epidemiology, and End Results cancer registries identified patients undergoing surgery for STS from 1988 to 2011. Data for patient age, tumor size, tumor grade, histologic subtype, sex, primary tumor location, and tumor depth were entered into the nomogram calculator for each patient. Discrimination was quantified using a concordance index. Calibration was assessed by comparing quintiles of nomogram-predicted probabilities of disease-specific mortality (DSM) with American Joint Committee on Cancer (AJCC) stage DSM. RESULTS: Overall, 9237 patients were identified with complete information needed for the nomogram. With a mean follow-up of 45 months, the concordance index for nomogram-predicted DSM with actual DSM was 0.74 for the entire cohort. For low- and high-grade tumors, this was 0.71 and 0.66, respectively. Kaplan-Meier curves showed better calibration for nomogram-predicted DSM when compared with AJCC staging. CONCLUSIONS: Our results validate the use of the MSKCC STS nomogram in the general population, with better predictive ability than AJCC staging. However, a concordance index of 0.74 suggests that further improvement in prognostication is needed, perhaps with biological markers or additional clinical variables. PMID- 26353761 TI - Reticulomics: Protein-Protein Interaction Studies with Two Plasmodesmata Localized Reticulon Family Proteins Identify Binding Partners Enriched at Plasmodesmata, Endoplasmic Reticulum, and the Plasma Membrane. AB - The endoplasmic reticulum (ER) is a ubiquitous organelle that plays roles in secretory protein production, folding, quality control, and lipid biosynthesis. The cortical ER in plants is pleomorphic and structured as a tubular network capable of morphing into flat cisternae, mainly at three-way junctions, and back to tubules. Plant reticulon family proteins (RTNLB) tubulate the ER by dimerization and oligomerization, creating localized ER membrane tensions that result in membrane curvature. Some RTNLB ER-shaping proteins are present in the plasmodesmata (PD) proteome and may contribute to the formation of the desmotubule, the axial ER-derived structure that traverses primary PD. Here, we investigate the binding partners of two PD-resident reticulon proteins, RTNLB3 and RTNLB6, that are located in primary PD at cytokinesis in tobacco (Nicotiana tabacum). Coimmunoprecipitation of green fluorescent protein-tagged RTNLB3 and RTNLB6 followed by mass spectrometry detected a high percentage of known PD localized proteins as well as plasma membrane proteins with putative membrane anchoring roles. Forster resonance energy transfer by fluorescence lifetime imaging microscopy assays revealed a highly significant interaction of the detected PD proteins with the bait RTNLB proteins. Our data suggest that RTNLB proteins, in addition to a role in ER modeling, may play important roles in linking the cortical ER to the plasma membrane. PMID- 26353763 TI - Intraoperative Parathormone Monitoring Mitigates Age-Related Variability in Targeted Parathyroidectomy for Patients with Primary Hyperparathyroidism. AB - BACKGROUND: Preoperative parathyroid localization studies, namely, sestamibi (MIBI) and surgeon-performed ultrasound (SUS), are commonly used for targeted parathyroidectomy (PTX) with intraoperative parathormone monitoring (IPM) in patients with primary hyperparathyroidism (pHPT). This study examined age-related variability in abnormal parathyroid gland localization for targeted PTX and the value of IPM across age groups. METHODS: A retrospective review examined prospectively collected data of 833 patients who underwent targeted PTX guided by IPM. The patients were stratified into three age groups as follows: younger [<47 years; mean -1 standard deviation (SD)], typical (47-73 years), and older (>73 years; mean +1 SD) based on an age distribution curve for pHPT. The accuracy, sensitivity, and positive predictive value (PPV) for MIBI, SUS, and IPM were analyzed and compared among age groups. Operative success was defined as eucalcemia for 6 months or longer after PTX, and operative failure was defined as elevated calcium and PTH levels within 6 months after PTX. RESULTS: Of the 833 patients, the youngest group had the highest accuracy and sensitivity for MIBI, SUS, and IPM compared with the older groups (p < 0.05). The accuracy and sensitivity of MIBI and SUS also decreased significantly with increased age (p < 0.05). Within all three age groups, IPM was consistently more accurate and sensitive than SUS or MIBI (p < 0.05). CONCLUSIONS: Age can significantly affect the accuracy and sensitivity of MIBI and SUS in targeted PTX for patients with pHPT. Across all age groups, IPM remains more accurate than preoperative localization studies. For the elderly, in whom multiglandular disease appears increased, surgeons should have a lower threshold for conversion to bilateral neck exploration. PMID- 26353764 TI - Value of Prophylactic Cervical Thymectomy in Parathyroid Hyperplasia. AB - BACKGROUND: In parathyroid hyperplasia (HPT), parathyroid glands within the cervical thymus are a cause for recurrence. As a result of differences in pathophysiology, variable practice patterns exist regarding performing bilateral cervical thymectomy (BCT) in primary hyperplasia versus hyperplasia from renal failure or familial disease. The objective of this study was to capture patients where thymic tissue was found with subtotal parathyroidectomy (PTX) and intended BCT, identify number of thymic supernumerary glands (SNGs), and determine overall cure rate. METHODS: Retrospective review of patients with four-gland exploration and intended BCT for HPT from 2000 to 2013 was performed. Identification of thymic tissue and SNGs were determined by operative/pathology reports. Univariate analysis identified differences in cure rate for patients undergoing subtotal PTX with or without BCT. RESULTS: Thymic tissue was found in 52 % of 328 primary HPT (19 % unilateral, 33 % bilateral), 77 % of 128 renal HPT (28 % unilateral, 49 % bilateral), and 100 % of familial HPT (24 % unilateral, 76 % bilateral) patients. Nine percent of primary, 18 % of renal, and 10 % of familial HPT patients had SNGs within thymectomy specimens. Cure rates of primary HPT patients with BCT were 99 % compared to 94 % in subtotal PTX alone. Renal HPT cure rates were 94 % with BCT compared to 89 % without BCT. CONCLUSIONS: Renal HPT patients benefited most in cure when thymectomy was performed. Although the rate of SNGs found in primary HPT was lower than renal HPT, the cure rate mimicked the pattern in renal disease. Furthermore, the incidences of SNGs in primary and familial HPT were similar. On the basis of these data, we advocate that BCT be considered in primary HPT when thymic tissue is readily identified. PMID- 26353765 TI - Transcoronary ethanol ablation for incessant ventricular tachycardia: a salvage technique when faced with left ventricular thrombus. PMID- 26353766 TI - Trends in incidence of infective endocarditis at the Medical Center of Alkmaar. AB - INTRODUCTION: Infective endocarditis (IE) is a life-threatening illness with a high morbidity and mortality, and with a rise in incidence in patients with prosthetic valves and cardiac devices. Recently the Dutch guidelines of IE prophylaxis have been revised, limiting IE prophylaxis to the highest-risk population. The aim of the present study was to investigate the incidence of IE and its trend between 2008-2013 in a regional hospital in the Netherlands. METHODS: This is an observational descriptive study of all patients who were admitted with IE to the Medical Center of Alkmaar (MCA) from 1 January 2008 to 31 December 2013. RESULTS: A total of 89 patients with IE, including 7 patients (7.9 %) with a cardiac device IE (CDIE), were identified. In 2008 there were 8 patients with IE, this increased to 26 patients in 2013. Patients with a prosthetic valve IE increased from 25 % in 2008 to 34.6 % in 2013. This increase was not seen in patients with CDIE. CONCLUSION: In the MCA we have observed an increase in patients with IE since 2010. This increase was in part attributable to prosthetic valve IE. A larger observational study is needed to investigate the increase of IE in the Netherlands. PMID- 26353767 TI - General practitioner reported incidence of Lyme carditis in the Netherlands. AB - BACKGROUND: Between 1994 and 2009, incidence rates of general practitioner (GP) consultations for tick bites and erythema migrans, the most common early manifestation of Lyme borreliosis, have increased substantially in the Netherlands. The current article aims to estimate and validate the incidence of GP-reported Lyme carditis in the Netherlands. METHODS: We sent a questionnaire to all GPs in the Netherlands on clinical diagnoses of Lyme borreliosis in 2009 and 2010. To validate and adjust the obtained incidence rate, medical records of cases of Lyme carditis reported by GPs in this incidence survey were reviewed and categorised according to likelihood of the diagnosis of Lyme carditis. RESULTS: Lyme carditis occurred in 0.2 % of all patients with GP-reported Lyme borreliosis. The adjusted annual incidence was six GP-reported cases of Lyme carditis per 10 million inhabitants, i.e. approximately ten cases per year in 2009 and 2010. CONCLUSIONS: We report the first incidence estimate for Lyme carditis in the Netherlands, validated by a systematic review of the medical records. Although Lyme carditis is an uncommon manifestation of Lyme borreliosis, physicians need to be aware of this diagnosis, in particular in countries where the incidence of Lyme borreliosis has increased during the past decades. PMID- 26353768 TI - Tricky ticks: the importance of Lyme carditis recognition. PMID- 26353770 TI - Child deaths plummet but many countries miss millennium development goal. PMID- 26353769 TI - Mechanistic-enriched models: integrating transcription factor networks and metabolic deregulation in cancer. AB - BACKGROUND: In the present paper we will examine methodological frameworks to study complex genetic diseases (e.g. cancer) from the stand point of theoretical computational biology combining both data-driven and hypothesis driven approaches. Our work focuses in the apparent counterpoint between two formal approaches to research in natural science: data- and hypothesis-driven inquiries. For a long time philosophers have recognized the mechanistic character of molecular biology explanations. On these grounds we suggest that hypothesis and data-driven approaches are not opposed to each other but that they may be integrated by the development of what we call enriched mechanistic models. METHODS: We will elaborate around a case study from our laboratory that analyzed the relationship between transcriptional de-regulation of sets of genes that present both transcription factor and metabolic activity while at the same time have been associated with the presence of cancer. The way we do this is by analyzing structural, mechanistic and functional approaches to molecular level research in cancer biology. Emphasis will be given to data integration strategies to construct new explanations. RESULTS: Such analysis has led us to present a mechanistic-enriched model of the phenomenon. Such model pointed out to the way in which regulatory and thermodynamical behavior of gene regulation networks may be analyzed by means of gene expression data obtained from genome-wide analysis experiments in RNA from biopsy-captured tissue. The foundations of the model are given by the laws of thermodynamics and chemical physics and the approach is an enriched version of a mechanistic explanation. CONCLUSION: After analyzing the way we studied the coupling of metabolic and transcriptional deregulation in breast cancer, we have concluded that one plausible strategy to integrate data driven and hypothesis driven approaches is by means of resorting to fundamental and well established laws of physics and chemistry since these provide a solid ground for assessment. PMID- 26353771 TI - Wicking teaching aged care facilities program: Innovative Practice. AB - This paper reports on the design of a program that aims to prototype teaching aged care facilities in Australia. Beginning in two Tasmanian residential aged care facilities, the intent of the program is to support large-scale inter professional student clinical placements, positively influence students' attitudes toward working in aged care and drive development of a high-performance culture capable of supporting evidence-based aged care practice. This is important in the context of aged care being perceived as an unattractive career choice for health professionals, reinforced by negative clinical placement experiences. The Teaching Aged Care Facilities Program features six stages configured around an action research/action learning method, with dementia being a key clinical focus. PMID- 26353773 TI - Outcomes in extremely preterm US infants improve, study finds. PMID- 26353772 TI - Study protocol of the TRICOLORE trial: a randomized phase III study of oxaliplatin-based chemotherapy versus combination chemotherapy with S-1, irinotecan, and bevacizumab as first-line therapy for metastatic colorectal cancer. AB - BACKGROUND: Metastatic colorectal cancer carries a poor prognosis and cannot be cured by currently available therapy. Chemotherapy designed to prolong survival and improve the quality of life (QOL) of patients is the mainstay of treatment. Standard regimens of FOLFOX/bevacizumab and CapeOX/bevacizumab can cause neurotoxicity, potentially disrupting treatment. The results of 3 phase II studies of combination therapy with S-1, irinotecan, and bevacizumab showed comparable efficacy to mFOLFOX6/bevacizumab and CapeOX/bevacizumab, without severe neurotoxicity. Therefore, the establishment and evaluation of S-1 containing irinotecan-based regimens for first-line treatment are expected to become more important. METHODS: The TRICOLORE trial is a multicenter, randomized, open-label, controlled phase III study which aims to evaluate the non-inferiority of combination therapy with S-1/irinotecan/bevacizumab (a 3-week regimen [SIRB] or 4-week regimen [IRIS/bevacizumab]) to oxaliplatin-based standard treatment (mFOLFOX6/bevacizumab or CapeOX/bevacizumab) in patients with metastatic colorectal cancer who had not previously received chemotherapy. Patients will be randomly assigned to either the control group (mFOLFOX6/bevacizumab or CapeOX/bevacizumab) or study group (SIRB or IRIS/bevacizumab). The target sample size is 450 patients. The primary endpoint is progression-free survival (PFS), and the secondary endpoints are overall survival (OS), response rate (RR), time to treatment failure (TTF), relative dose intensity (RDI), the incidence and severity of adverse events, quality of life (QOL), quality-adjusted life years (QALY), health care costs, and relations between biomarkers and treatment response (translational research, TR). DISCUSSION: The results of this study will provide important information that will help to improve the therapeutic strategy for metastatic colorectal cancer, and we believe that this study is very meaningful from the perspective of comparative effectiveness research. TRIAL REGISTRATION: UMIN000007834. PMID- 26353774 TI - Human cord blood-derived platelet lysate enhances the therapeutic activity of adipose-derived mesenchymal stromal cells isolated from Crohn's disease patients in a mouse model of colitis. AB - INTRODUCTION: Due to their immunomodulatory properties, mesenchymal stromal cells (MSCs) have been used for auto-immune disease treatment. Crohn disease (CD) and ulcerative colitis are two major inflammatory bowel diseases (IBDs), resulting from pathological immune responses to environmental or microbial antigens. Preclinical and clinical studies have suggested that MSC-based cellular therapy hold promising potential for IBD treatment. However, open issues include the selection of the proper cell dose, the source and the optimal route of administration of MSCs for more effective results. Platelet lysate has gained clinical interest due to its efficacy in accelerating wound healing. Thus, we propose to combine the administration of MSCs with a human umbilical cord blood derived platelet lysate (hCBPL) as a novel strategy to improve MSC-based therapy for IBD resolution. METHODS: Colitis was induced in 8-week-old C57BL/6J mice by daily oral administration of dextran sulphate sodium (DSS) (1.5 % w/v in tap water) for 9 days. MSCs were isolated from adipose tissue of CD patients (adCD MSCs), expanded in proliferation medium, resuspended in hCBPL or PBS and administrated via enema for three times (1 * 10(6) cells/mouse/time) every other day starting on day +7 from DSS induction. The colitis evolution was evaluated by daily monitoring of body weight, stool consistency and bleeding. Histopathological analysis was performed. Inflammatory cytokine plasma levels were determined. adCD-MSCs stained with lipophilic membrane dye Nile Red, were injected in DSS mice as described above. Colon section of mice sacrificed 24 hours after last cell administration, were analyzed by confocal microscopy. RESULTS: We found that adCD-MSCs could be easily isolated and expanded from CD patients. Upon injection, adCD-MSCs exerted a therapeutic effect on DSS-induced colitis. Moreover, hCBPL increased adCD-MSCs efficacy by significantly reducing colitis scores, extension of the colon inflamed area and plasma levels of inflammatory mediators. Finally, Nile Red staining of MSCs is very efficient, stable and does not impair their vitality and function. Nile Red-labelling was clearly detected in the colitic area of adCD-MSCs injected mice and it was significantly brighter in the colon sections of mice that had received adCD MSCs/hCBPL. CONCLUSIONS: In summary, with this study we propose a novel and promising adCD-MSC/hCBPL-based therapy for refractory IBDs. PMID- 26353775 TI - Transfemoral amputee recovery strategies following trips to their sound and prosthesis sides throughout swing phase. AB - BACKGROUND: Recovering from trips is challenging for transfemoral amputees, and attempts often result in falls. Better understanding of the effects of the sensory-motor deficits brought by amputation and the functional limitations of prosthetic devices could help guide therapy and fall prevention mechanisms in prostheses. However, how transfemoral amputees attempt to recover from trips on the sound and prosthesis sides throughout swing phase is poorly understood. METHODS: We tripped eight able-bodied subjects and eight unilateral transfemoral amputees wearing their prescribed prostheses. The protocol consisted of six repetitions of 6 and 4 points throughout swing phase, respectively. We compared recovery strategies in able-bodied, sound side and prosthesis side limbs. The number of kinematic recovery strategies used, when they were used throughout swing phase, and kinematic characteristics (tripped limb joint angles, bilateral trochanter height and time from foot arrest to foot strike) of each strategy were compared across limb groups. Non-parametric statistical tests with corrections for post-hoc tests were used. RESULTS: Amputees used the same recovery strategies as able-bodied subjects on both sound and prosthesis sides, although not all subjects used all strategies. Compared to able-bodied subjects, amputees used delayed-lowering strategies less often from 30-60 % of swing phase on the sound side, and from 45-60 % of swing phase on the prosthesis side. Within-strategy kinematic differences occurred across limbs; however, these differences were not consistent across all strategies. Amputee-specific recovery strategies-that are not used by control subjects-occurred following trips on both the sound and prosthesis sides in mid- to late swing. CONCLUSIONS: Collectively, these results suggest that sensory input from the distal tripped leg is not necessary to trigger able-bodied trip recovery strategies. In addition, the differences between sound and prosthesis side recoveries indicate that the ability of the support leg might be more critical than that of the tripped leg when determining the response to a trip. The outcomes of this study have implications for prosthesis control, suggesting that providing correct and intuitive real-time selection of typical able-bodied recovery strategies by a prosthetic device when it is the tripped and the support limb could better enable balance recovery and avoid falls. PMID- 26353776 TI - Aspirin and P2Y12 inhibition attenuate platelet-induced ovarian cancer cell invasion. AB - BACKGROUND: Platelet-cancer cell interactions play a key role in successful haematogenous metastasis. Disseminated malignancy is the leading cause of death among ovarian cancer patients. It is unknown why different ovarian cancers have different metastatic phenotypes. To investigate if platelet-cancer cell interactions play a role, we characterized the response of ovarian cancer cell lines to platelets both functionally and at a molecular level. METHODS: Cell lines 59 M and SK-OV-3 were used as in vitro model systems of metastatic ovarian cancer. Platelet cloaking of each cell line was quantified by flow cytometry. Matrigel invasion chamber assays were used to assess the invasive capacity of the cell lines. The induction of an EMT was assessed by morphology analysis and by gene expression analysis of a panel of 11 EMT markers using TaqMan RT-PCR. RESULTS: SK-OV-3 cells adhered to and activated more platelets than 59 M cells (p = 0.0333). Platelets significantly promoted the ability of only SK-OV-3 cells to invade (p <= 0.0001). Morphology and transcritpome analysis indicated that platelets induce an epithelial-to-mesenchymal transition phenotype in both cells lines, with a more exaggerated response in SK-OV-3 cells. Next, we investigated if antiplatelet agents could abrogate the platelet-induced aggressive phenotype in SK-OV-3 cells. Both aspirin (p <= 0.05) and 2-methylthioadenosine 5' monophosphate triethylammonium salt hydrate (P2Y12 inhibitor; p <= 0.01) significantly decreased their invasion capacity, and effectively reverted invasion to levels comparable to SK-OV-3 cells alone. CONCLUSION: While there is increasing evidence for the cancer-protective effect of aspirin, this study suggests P2Y12 inhibition may also play a role. Understanding these complex interactions between platelets and cancer cells could ultimately allow the establishment of therapies tailored to inhibiting metastasis, thus significantly reducing cancer morbidity. PMID- 26353777 TI - Metagenomic and metatranscriptomic inventories of the lower Amazon River, May 2011. AB - BACKGROUND: The Amazon River runs nearly 6500 km across the South American continent before emptying into the western tropical North Atlantic Ocean. In terms of both volume and watershed area, it is the world's largest riverine system, affecting elemental cycling on a global scale. RESULTS: A quantitative inventory of genes and transcripts benchmarked with internal standards was obtained at five stations in the lower Amazon River during May 2011. At each station, metagenomes and metatranscriptomes were obtained in duplicate for two microbial size fractions (free-living, 0.2 to 2.0 MUm; particle-associated, 2.0 to 297 MUm) using 150 * 150 paired-end Illumina sequencing. Forty eight sample datasets were obtained, averaging 15 * 10(6) potential protein-encoding reads each (730 * 10(6) total). Prokaryotic metagenomes and metatranscriptomes were dominated by members of the phyla Actinobacteria, Planctomycetes, Betaproteobacteria, Verrucomicrobia, Nitrospirae, and Acidobacteria. The actinobacterium SCGC AAA027-L06 reference genome recruited the greatest number of reads overall, with this single bin contributing an average of 50 billion genes and 500 million transcripts per liter of river water. Several dominant taxa were unevenly distributed between the free-living and particle-associated size fractions, such as a particle-associated bias for reads binning to planctomycete Schlesneria paludicola and a free-living bias for actinobacterium SCGC AAA027 L06. Gene expression ratios (transcripts to gene copy ratio) increased downstream from Obidos to Macapa and Belem, indicating higher per cell activity of Amazon River bacteria and archaea as river water approached the ocean. CONCLUSION: This inventory of riverine microbial genes and transcripts, benchmarked with internal standards for full quantitation, provides an unparalleled window into microbial taxa and functions in the globally important Amazon River ecosystem. PMID- 26353778 TI - Tax fraud GP is struck off for persistent dishonesty. PMID- 26353779 TI - Fundus Autofluorescence Captured With a Nonmydriatic Retinal Camera in Vegetarians Versus Nonvegetarians. AB - BACKGROUND: A baseline level of lipofuscin in the retinal pigment epithelium (RPE) is inevitable with age, but increased levels due to increased oxidative stress can result in deleterious vision loss at older ages. As earlier detection of differences in levels can lead to superior preventative management, we studied the relationship between lipofuscin accumulation and dietary lifestyle (vegetarian vs. nonvegetarian) in the younger, healthy South Asian population using retinal fundus autofluorescence (FAF) imaging. METHODS: In this pilot study, we examined 37 healthy subjects (average age 23 years +/- 1) all undergoing similar stress levels as medical students at Rutgers New Jersey Medical School. Levels of lipofuscin concentrations were imaged using a FAF retinal camera (Canon CX-1). Two images (color and FAF) were captured of the left eye and included in the analysis. FAF quantitative scoring was measured in 2 regions of the captured image, the papillo-macular region (P) and the macula (M), by determining the grayscale score of a 35.5 mm(2) rectangle in the respective regions. Standardized scores (corrected to remove baseline fluorescence) were then obtained. Means, standard deviations, and t tests were performed for comparisons. RESULTS: Fundus autofluorescence scores of regions P and M were significantly different (P < .05) between groups. Region P was further standardized and results remained significant. CONCLUSIONS: Our preliminary results show that in this cohort, vegetarians had statistically significant lower levels of autofluorescence. These findings can have potential implications regarding long-term retinal health and risk for developing certain diseases over decades in subjects at risk for vision-threatening diseases. PMID- 26353780 TI - Is the Correlation of HbA1c to Average Glucose Predictable in Individuals With Sickle Cell Trait? PMID- 26353781 TI - Impact of Frequent and Persistent Use of Continuous Glucose Monitoring (CGM) on Hypoglycemia Fear, Frequency of Emergency Medical Treatment, and SMBG Frequency After One Year. AB - BACKGROUND: We assessed the impact of "almost daily" use of continuous glucose monitoring (CGM) in adults with type 1 diabetes who had at least 1 year of CGM experience. METHODS: In this single-center survey, we utilized a 16-item questionnaire to assess changes hypoglycemia fear, incidence of emergency medical treatment and utilization of self-monitoring of blood glucose (SMBG) before and after 1 year of CGM use. Participation was restricted to individuals who used the same brand of CGM system to avoid confounding responses due to differences between commercial devices. Participants were recruited on an "as-seen" basis from a major, urban internal medicine clinic and associated diabetes education center. The questionnaire was completed during the clinic visit. Responses to the survey were analyzed by standard descriptive statistics. RESULTS: Seventy-four patients completed the survey: 42.9 years (range: 23-71 years), 38 (51%) female, 59 current insulin pump users. Most (84%) reported wearing their devices "almost daily" (n = 58) or 3 weeks per month (n = 4). "Almost daily" users reported an 86% reduction in incidence of emergency medical treatment events (P = .0013) and >50% reduction in daily SMBG frequency (P < .0001). Reductions in hypoglycemia fear were apparent but not statistically significant (P = .7359). CONCLUSIONS: "Almost daily" use of CGM with the Dexcom G4 system reduced incidence of emergency treatment events and daily SMBG utilization among survey respondents and a trend toward reduced hypoglycemia fear. This may indicate cost savings in reduction of emergency medical intervention and likely improved quality of life without increasing safety concerns related to hypoglycemia. PMID- 26353782 TI - DKK1 is a potential novel mediator of cisplatin-refractoriness in non-small cell lung cancer cell lines. AB - BACKGROUND: Platinum compounds are the mainstay of chemotherapy for lung cancer. Unfortunately treatment failure remains a critical issue since about 60% of all non-small cell lung cancer (NSCLC) patients display intrinsic platinum resistance. METHODS: We analyzed global gene expression profiles of NSCLC clones surviving a pulse treatment with cisplatin and mapped deregulated signaling networks in silico by Ingenuity Pathway Analysis (IPA). Further validation was done using siRNA. RESULTS: The pooled cisplatin-surviving NSCLC clones from each of the biological replicates demonstrated heterogeneous gene expression patterns both in terms of the number and the identity of the altered genes. Genes involved in Wnt signaling pathway (Dickkopf-1, DKK1), DNA repair machinery (XRCC2) and cell-cell/cell-matrix interaction (FMN1, LGALS9) were among the top deregulated genes by microarray in these replicates and were validated by q-RT-PCR. We focused on DKK1 which previously was reported to be overexpressed in NSCLC patients. IPA network analysis revealed coordinate up-regulation of several DKK1 transcriptional regulators (TCF4, EZH2, DNAJB6 and HDAC2) in cisplatin-surviving clones from that biological replicate. Knockdown of DKK1 by siRNA sensitized for cisplatin in two different NSCLC cell lines and in ovarian A2780 cells, but not in the A2780 cis subline made resistant to cisplatin by chronic exposure, suggesting a role of DKK1 in intrinsic but not acquired platinum refractoriness. CONCLUSIONS: We identified DKK1 as a possible marker of a cisplatin-refractory phenotype and as a potential novel therapeutic target to improve platinum response of NSCLC cells. PMID- 26353783 TI - Leukotriene enhances NMDA-induced inward currents in dorsal horn neurons of the rat spinal cord after peripheral nerve injury. AB - BACKGROUND: LTB4 is classified as a leukotriene (LT), a group of lipid mediators that are derived from arachidonic acid. It is recognized that leukotrienes are involved in the pathogenesis of many diseases, including peripheral inflammatory pain. However, little is known about the effects of leukotrienes on the spinal dorsal horn during neuropathic pain. Previously, we reported that there was increased expression of 5-lipoxygenase (5-LO) at spinal microglia, and the leukotriene B4 receptor 1 (BLT1), a high affinity receptor of LTB4, in spinal neurons in spared nerve injury (SNI) model rats. In the present study, we examined the effects of LTB4 on spinal dorsal horn neurons in both naive and SNI model rats using patch-clamp methods. RESULTS: Bath application of LTB4 did not change AMPA receptor-mediated spontaneous excitatory postsynaptic currents (sEPSCs) or membrane potentials. However, we found that LTB4 enhanced the amplitude of NMDA receptor-mediated sEPSCs and significantly increased exogenous NMDA-induced inward currents in SNI model rats. This increase of inward currents could be inhibited by a selective LTB4 antagonist, U75302, as well as a GDP-beta S, a G-protein inhibitor. These results indicate that both increased LTB4 from spinal microglia or increased BLT1 in spinal neurons after peripheral nerve injury can enhance the activity of NMDA receptors through intracellular G proteins in spinal dorsal horn neurons. CONCLUSION: Our findings showed that LTB4, which may originate from microglia, can activate BLT1 receptors which are expressed on the membrane of spinal dorsal horn neurons during neuropathic pain. This glia-neuron interaction induces the enhancement of NMDA currents through intracellular G-proteins. The enhancement of NMDA receptor sensitivity of dorsal horn neurons may lead to central sensitization, leading to mechanical pain hypersensitivity. PMID- 26353784 TI - A study protocol for Truce: a pragmatic controlled trial of a seven-week acceptance and commitment therapy program for young people who have a parent with cancer. AB - BACKGROUND: This paper presents the rationale and study protocol for a pragmatic controlled effectiveness trial of Truce, a prevention-based selective intervention targeting the significant mental health needs of young people who have a parent with cancer. METHODS/DESIGN: Truce is a seven week, facilitated, face-to-face group program. The design is a 2 groups (intervention vs control) x 3 (pre-treatment vs post-treatment vs 2 month follow-up) repeated measures. Allocation to groups will be dependent upon recruitment; when groups have sufficient numbers, they will be assigned to the intervention condition, but participants recruited without a viable group will be assigned to the wait-list control condition. Eligible participants are young people aged 14 to 22 years who have a parent diagnosed with cancer within the last 5 years. Wait-list controls are offered the opportunity to participate in the program once they have completed their follow-up questionnaires. The target sample size is 65 participants in each condition. The primary hypothesis is that participants in the intervention will show significant reductions in distress and increases in psychological well-being relative to participants in the wait-list control group, and these effects will continue through two-month follow-up. Mixed-models analysis of variance will be used to measure differences between the two conditions. Secondary analyses will focus on variables which may relate to the effectiveness of the intervention: ACT-related concepts of experiential avoidance and mindfulness, family functioning, unmet needs and demographic variables. We will also assess program fidelity and satisfaction. DISCUSSION: The development and evaluation of a manualised intervention for young people with a parent with cancer responds to a gap in the provision of empirically-based psychological support for this vulnerable group. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ACTRN12615000761561. Registered 22(nd) July 2015. PMID- 26353785 TI - Michael Marmot: Evidence based optimist. PMID- 26353786 TI - Collagen peptide supplementation in combination with resistance training improves body composition and increases muscle strength in elderly sarcopenic men: a randomised controlled trial. AB - Protein supplementation in combination with resistance training may increase muscle mass and muscle strength in elderly subjects. The objective of this study was to assess the influence of post-exercise protein supplementation with collagen peptides v. placebo on muscle mass and muscle function following resistance training in elderly subjects with sarcopenia. A total of fifty-three male subjects (72.2 (sd 4.68) years) with sarcopenia (class I or II) completed this randomised double-blind placebo-controlled study. All the participants underwent a 12-week guided resistance training programme (three sessions per week) and were supplemented with either collagen peptides (treatment group (TG)) (15 g/d) or silica as placebo (placebo group (PG)). Fat-free mass (FFM), fat mass (FM) and bone mass (BM) were measured before and after the intervention using dual-energy X-ray absorptiometry. Isokinetic quadriceps strength (IQS) of the right leg was determined and sensory motor control (SMC) was investigated by a standardised one-leg stabilisation test. Following the training programme, all the subjects showed significantly higher (P<0.01) levels for FFM, BM, IQS and SMC with significantly lower (P<0.01) levels for FM. The effect was significantly more pronounced in subjects receiving collagen peptides: FFM (TG +4.2 (sd 2.31) kg/PG +2.9 (sd 1.84) kg; P<0.05); IQS (TG +16.5 (sd 12.9) Nm/PG +7.3 (sd 13.2) Nm; P<0.05); and FM (TG -5.4 (sd 3.17) kg/PG -3.5 (sd 2.16) kg; P<0.05). Our data demonstrate that compared with placebo, collagen peptide supplementation in combination with resistance training further improved body composition by increasing FFM, muscle strength and the loss in FM. PMID- 26353787 TI - A randomized trial of a minimal intervention for sexual concerns after cancer: a comparison of self-help and professionally delivered modalities. AB - BACKGROUND: Information and discussion of sexual changes with a health professional is a high priority for many cancer patients in order to assist with sexual changes and ensure that sexual intimacy does not cease post-cancer. The PLISSIT model is widely recommended as a framework for providing sexual information and support, allowing for the discussion of sexual changes at various levels of increasing intensity. The aim of the present study is to evaluate the early stages of the PLISSIT model by examining the relative efficacy of written information provision about cancer related sexual changes, and information provision accompanied by a single session of counselling, for people with cancer and their partners, across a range of cancer types. METHOD: Eighty-eight people with cancer and 53 partners across a range of sexual and non-sexual cancers, took part in a randomised trial which adopted mixed method analysis to examine changes in psychological wellbeing, quality of life, relationship satisfaction and communication, and sexual functioning, following written information provision about cancer related sexual changes (self-help condition; SH), or written information accompanied by a single session of counselling (health professional condition; HP). RESULTS: Ratings of the usefulness and efficacy of the SH and HP interventions, collected through analysis of Likert scales, open ended survey items and interviews, indicated that both conditions were found to be useful and efficacious by the majority of participants, serving to increase awareness of sexuality, improve couple communication about sex, and help in the management of sexual changes, through the exploration of non-coital sexual practices. In contrast, the quantitative analysis of standardized instruments found no significant improvements in psychological wellbeing, quality of life, relationship satisfaction and communication, or sexual functioning. There were significant reductions in self-silencing in the HP condition, and a trend towards increases in sexual satisfaction across both conditions. CONCLUSION: These results offer support for the early stages of the PLISSIT model, in terms of normalization and increased awareness of sexual changes after cancer, increased couple communication about sexual changes, and legitimation of exploration of a range of non-coital sexual practices and intimacy. However, more complex and intensive interventions are needed to address sexual functioning and psychological wellbeing. The findings provide support for the proposition that providing permission to discuss sexuality should be the core feature underpinning all stages of interventions designed to provide sexuality information and support for people with cancer and their partners, and also demonstrate the potential importance of limited information and specific suggestions. TRIAL REGISTRATION: This study was registered in the Australian New Zealand Clinical Trials Registry. ( ACTRN12615000399594 ) on 29 April 2015. PMID- 26353788 TI - Limited changes in spinal lamina I dorsal horn neurons following the cytotoxic ablation of non-peptidergic C-fibers. AB - BACKGROUND: Non-peptidergic nociceptive neurons are a sub-population of small diameter primary sensory neurons that comprise approximately 50 % of the C fiber population. Together with the peptidergic sub-population, they transmit nociceptive information from the periphery to the superficial dorsal horn of the spinal cord. Despite the numerous studies investigating the role of the non peptidergic primary afferents, their role in normal nociception and in pain remains poorly understood. Our lab has previously demonstrated that, in rat models of neuropathic and inflammatory pain, there is a de novo expression of substance P receptors (NK-1r) by lamina I pyramidal projection neurons, a neuronal population that normally does not express these receptors. RESULTS: In this study, we used a ribosomal toxin, saporin, conjugated to the lectin IB4 to selectively ablate the non-peptidergic nociceptive C fibers, to investigate if the loss of these fibers was enough to induce a change in NK-1r expression by lamina I projection neurons. IB4-saporin treatment led to the permanent ablation of the IB4-positive afferents but also to a small non-significant reduction in CGRP-positive afferents. An overall increase in immunoreactivity for the NK-1r was observed in lamina I projection neurons, however, the lack of non-peptidergic afferents did not increase the number of lamina I pyramidal projection neurons immunoreactive for the receptor. CONCLUSIONS: Our results demonstrate that the deletion of the non-peptidergic afferents, at the L4-L5 spinal levels, is not sufficient to trigger the de novo expression of NK-1r by projection pyramidal neurons but increases the expression of NK-1r in fusiform and multipolar projection neurons. Furthermore, our data suggest that a neuropathic component is essential to trigger the expression of NK-1r by pyramidal neurons. PMID- 26353789 TI - Fish oil in knee osteoarthritis: a randomised clinical trial of low dose versus high dose. AB - OBJECTIVES: To determine whether high-dose fish oil is superior to low-dose supplementation for symptomatic and structural outcomes in knee osteoarthritis (OA). METHODS: A randomised, double-blind, multicentre trial enrolled 202 patients with knee OA and regular knee pain. They were randomised 1:1 to high dose fish oil (4.5 g omega-3 fatty acids) 15 mL/day or (2) low-dose fish oil (blend of fish oil and sunola oil; ratio of 1:9, 0.45 g omega-3 fatty acids) 15 mL/day. The primary endpoints were Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain score at 3, 6, 12 and 24 months, and change in cartilage volume at 24 months. Secondary outcomes included WOMAC function, quality of life, analgesic and non-steroidal anti-inflammatory drug use and bone marrow lesion score. RESULTS: Although there was improvement in both groups, the low-dose fish oil group had greater improvement in WOMAC pain and function scores at 2 years compared with the high-dose group, whereas between-group differences at 1 year did not reach statistical significance. There was no difference between the two groups in cartilage volume loss at 2 years. For other secondary endpoints, there was no difference between the two groups at 2 years. CONCLUSIONS: In people with symptomatic knee OA, there was no additional benefit of a high-dose fish oil compared with low-dose fish oil. The combination comparator oil appeared to have better efficacy in reducing pain at 2 years, suggesting that this requires further investigation. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ACTRN 12607000415404). PMID- 26353790 TI - Tofacitinib regulates synovial inflammation in psoriatic arthritis, inhibiting STAT activation and induction of negative feedback inhibitors. AB - BACKGROUND: Psoriatic arthritis (PsA) is a chronic inflammatory disease, characterised by synovitis and destruction of articular cartilage/bone. Janus kinase and signal transducer and activator of transcription (JAK-STAT) signalling pathway is implicated in the pathogenesis of PsA. OBJECTIVES: To examine the effect of tofacitinib (JAK inhibitor) on proinflammatory mechanisms in PsA. METHODS: Primary PsA synovial fibroblasts (PsAFLS) and ex vivo PsA synovial explants were cultured with tofacitinib (1 uM). PhosphoSTAT3 (pSTAT3), phosphoSTAT1 (pSTAT1), suppressor of cytokine signaling-3 (SOCS3), protein inhibitor of activated Stat3 (PIAS3) and nuclear factor kappa B cells (NFkappaBp65) were quantified by western blot. The effect of tofacitinib on PsAFLS migration, invasion, Matrigel network formation and matrix metallopeptidase (MMP)2/9 was quantified by invasion/migration assays and zymography. Interleukin (IL)-6, IL-8, IFN-gamma-inducible protein 10 (IP-10) monocyte chemoattractant protein (MCP)-1, IL-17, IL-10, MMP3 and tissue inhibitor of metalloproteinases 3 (TIMP3) were assessed by ELISA. RESULTS: Tofacitinib significantly decreased pSTAT3, pSTAT1, NFkappaBp65 and induced SOCS3 and PIAS3 expression in PsAFLS and synovial explant cultures (p<0.05). Functionally, PsAFLS invasion, network formation and migration were inhibited by tofacitinib (all p<0.05). In PsA explant, tofacitinib significantly decreased spontaneous secretion of IL-6, IL-8, MCP-1, MMP9/MMP2, MMP3 (all p<0.05) and decreased the MMP3/TIMP3 ratio (p<0.05), with no effect observed for IP-10 or IL-10. CONCLUSIONS: This study further supports JAK-STAT inhibition as a therapeutic target for the treatment of PsA. PMID- 26353791 TI - When should the umbilical cord be clamped? PMID- 26353792 TI - The Deleted in Liver Cancer 1 (Dlc1) tumor suppressor is haploinsufficient for mammary gland development and epithelial cell polarity. AB - BACKGROUND: Deleted in Liver Cancer 1 (Dlc1) is a tumor suppressor gene, which maps to human chromosome 8p21-22 and is found frequently deleted in many cancers including breast cancer. The promoter of the remaining allele is often found methylated. The Dlc1 gene encodes a RhoGAP protein that regulates cell proliferation, migration and inhibits cell growth and invasion when restored in Dlc1 deficient tumor cell lines. This study focuses on determining the role of Dlc1 in normal mammary gland development and epithelial cell polarity in a Dlc1 gene trapped (gt) mouse. METHODS: Mammary gland whole mount preparations from 10 week virgin heterozygous Dlc1(gt/+) gene-trapped mice were compared with age matched wild type (WT) controls. Hematoxylin-Eosin (H&E) and Masson's Trichrome staining of histological sections were carried out. Mammary glands from Dlc1(gt/+) mice and WT controls were enzymatically digested with collagenase and dispase and then cultured overnight to deplete hematopoietic and endothelial cells. The single cell suspensions were then cultured in Matrigel for 12 days. To knockdown Dlc1 expression, primary WT mammary epithelial cells were infected with short hairpin (sh) RNA expressing lentivirus or with a scrambled shRNA control. RESULTS: Dlc1(gt/+) mice showed anomalies in the mammary gland that included increased ductal branching and deformities in terminal end buds and branch points. Compared to the WT controls, Masson's Trichrome staining showed a thickened stromal layer with increased collagen deposition in mammary glands from Dlc1(gt/+) mice. Dlc1(gt/+) primary mammary epithelial cells formed increased solid acinar spheres in contrast with WT and scrambled shRNA control cells, which mostly formed hollow acinar structures when plated in 3D Matrigel cultures. These solid acinar structures were similar to the acinar structures formed when Dlc1 gene expression was knocked down in WT mammary cells by shRNA lentiviral transduction. The solid acinar structures were not due to a defect in apoptosis as determined by a lack of detectible cleaved caspase 3 antibody staining. Primary mammary cells from Dlc1(gt/+) mice showed increased RhoA activity compared with WT cells. CONCLUSIONS: The results illustrate that decreased Dlc1 expression can disrupt the normal cell polarization and mammary ductal branching. Altogether this study suggests that Dlc1 plays a role in maintaining normal mammary epithelial cell polarity and that Dlc1 is haploinsufficient. PMID- 26353793 TI - Clinical complications during treatment with a modified Herbst appliance in combination with a lingual appliance. AB - OBJECTIVE: To assess the types and frequencies of clinical complications experienced when using a modified lingual Herbst appliance and to compare these with those associated with conventional Herbst appliances reported in the literature. METHODS: Treatment records for 35 consecutive subjects treated during the observation period from October 2013 to August 2014 who received a combination of a lingual appliance and a modified Herbst appliance (WIN, DW LingualSystems) were assessed for complications linked to Herbst treatment phase. Complications were analyzed descriptively, and complication-free intervals were calculated using Kaplan-Meier plots. To enable a comparison with data reported in the literature, the cumulative treatment time for all subjects was divided by the total number of complications. RESULTS: 71.4% of Herbst treatments were free from complications (n = 25). Complications were seen on 13 occasions (8 instances of Herbst attachment loosening, 5 L-Pin fractures). Most of these complications could be fixed chair side utilizing simple clinical measures. Considering all complications as identical statistical events, the percentage of treatments free from complications would be 88% for 100 days, 70% for 200 days and 56.8% for 300 days. For severe complications, the averaged complication-free treatment interval was found to be 27.8 months. CONCLUSION: In terms of clinical sturdiness, and taking into consideration the step-wise mode of activation used here as well as the differences in the design of the various Herbst appliances, the WIN-Herbst appliance was found to be superior to comparable vestibular Herbst appliances, as well as the banded Herbst appliance belonging to the preceding generation of customized lingual systems. Success in treatment of non-compliant Angle Class II correction is considered to have better predictability using the modified anchorage strategy of the WIN-Herbst appliance. PMID- 26353794 TI - Recent advances in the understanding and management of delayed puberty. AB - Delayed puberty, especially in boys, is a common presentation in paediatrics. Recent advances have improved our understanding of the neuroendocrine, genetic and environmental factors controlling pubertal development, and hence inform the pathophysiology of delayed puberty. The discovery of kisspeptin signalling through its receptor identified neuroendocrine mechanisms controlling the gonadotrophin-releasing hormone (GnRH) pulse generator at the onset of puberty. Genetic mechanisms from single gene mutations to single nucleotide polymorphism associated with delayed puberty are being identified. Environmental factors, including nutritional factors and endocrine disruptors, have also been implicated in changes in secular trends and abnormal timing of puberty. Despite these advances, the key clinical question is to distinguish delayed puberty associated with an underlying pathology or hypogonadism from constitutional delay in growth and puberty, which remains challenging as biochemical tests are not always discriminatory. The diagnostic accuracies of newer investigations, including 36 hour luteinising hormone releasing hormone (LHRH) tests, GnRH-agonist tests, antimullerian hormone and inhibin-B, require further evaluation. Sex hormone replacement remains the main available treatment for delayed puberty, the choice of which is largely dictated by clinical practice and availability of the various sex steroid preparations. Spontaneous reversal of hypogonadism has been reported in boys with idiopathic hypogonadotrophic hypogonadism after a period of sex steroid treatment, highlighting the importance of reassessment at the end of pubertal induction. Novel therapies with a more physiological basis such as gonadotrophins or kisspeptin-agonist are being investigated for the management of hypogonadotrophic hypogonadism. Careful clinical assessment and appreciation of the normal physiology remain the key approach to patients with delayed puberty. PMID- 26353795 TI - US oncologists update guidance on DNA sequencing in clinical practice. PMID- 26353796 TI - Return to Play in National Football League Players After Operative Jones Fracture Treatment. AB - BACKGROUND: Jones fractures commonly occur in professional athletes and operative treatment remains the standard of care in this patient population. In our clinical experience, an aggressive postoperative rehabilitation protocol for National Football League (NFL) players with an average return to play (RTP) between 8 and 10 weeks can have successful outcomes with few complications. The purpose of this study was to quantify RTP and rate of complications, including nonunion, refracture, and reoperation among a cohort of NFL players with operatively treated Jones fractures. METHODS: Between 2004 and 2014, 25 consecutive NFL players who underwent acute Jones fracture fixation by a single surgeon were reviewed. Operative treatment for the majority of patients involved fixation with a Jones-specific intramedullary screw and iliac crest bone marrow aspirate with demineralized bone matrix injected at the fracture site. Additionally, our protocol involved the use of noninvasive bone stimulators, application of customized orthoses, and an aggressive patient-specific rehabilitation protocol. Patient demographics were recorded along with position played, seasons played after surgery, RTP, and complications. RTP was defined as the ability to play in a single regular-season NFL game after surgery. At the time of surgery, average age for all patients was 24.0 years and BMI 31.0. RESULTS: Player positions included 8 wide receivers, 4 linebackers, 4 tight ends, 2 defensive tackles, 2 cornerbacks, 1 offensive tackle, 1 center, 1 tackle, 1 defensive end, and 1 quarterback. Seventy-six percent of players underwent operative fixation during their first 3 seasons. Forty-eight percent were diagnosed before or during their rookie (first) season.RTP was 100% for all players and 80% were still playing at time of publication. Three patients (12.0%) refractured and required revision surgery. Time until RTP was influenced by other variables and difficult to measure because many surgeries were performed early in the offseason. All 9 players who underwent surgery between July and October, and were therefore eligible to return to play in the same season, had an average RTP of 8.7 weeks (range 5.9-13.6). CONCLUSION: With an appropriately placed intramedullary screw and an aggressive rehabilitation protocol, early RTP was achievable with a low refracture rate in professional athletes. All NFL players in this series were able to return to play after surgery. We observed that these injuries were more likely to occur in the first 3 seasons of play and in wide receivers, linebackers, and tight ends. This at-risk subset of players may benefit from improved preventative measures. LEVEL OF EVIDENCE: Level IV, retrospective case series. PMID- 26353797 TI - Post resuscitation care of out-of-hospital cardiac arrest patients in the Nordic countries: a questionnaire study. AB - BACKGROUND: Aim of this study was to compare post resuscitation care of out-of hospital cardiac arrest (OHCA) patients in Nordic (Denmark, Finland, Iceland, Norway, Sweden) intensive care units (ICUs). METHODS: An online questionnaire was sent to Nordic ICUs in 2012 and was complemented by an additional one in 2014. RESULTS: The first questionnaire was sent to 188 and the second one to 184 ICUs. Response rates were 51 % and 46 %. In 2012, 37 % of the ICUs treated all patients resuscitated from OHCA with targeted temperature management (TTM) at 33 degrees C. All OHCA patients admitted to the ICU were treated with TTM at 33 degrees C more often in Norway (69 %) compared to Finland (20 %) and Sweden (25 %), p 0.02 and 0.014. In 2014, 63 % of the ICUs still use TTM at 33 degrees C, but 33 % use TTM at 36 degrees C. Early coronary angiography (CAG) and possible percutaneous coronary intervention (PCI) was routinely provided for all survivors of OHCA in 39 % of the hospitals in 2012 and in 28 % of the hospitals in 2014. Routine CAG for all actively treated victims of OHCA was performed more frequently in Sweden (51 %) and in Norway (54 %) compared to Finland (13 %), p 0.014 and 0.042. CONCLUSIONS: Since 2012, TTM at 36 degrees C has been implemented in some ICUs, but TTM at 33 degrees C is used in majority of the ICUs. TTM at 33 or 36 degrees C and primary CAG are not routinely provided for all OHCA survivors and the criteria for these and ICU admission are variable. Best practices as a uniform approach to the optimal care of the resuscitated patient should be sought in the Nordic Countries. PMID- 26353799 TI - Asymmetry of Inframammary Folds in Patients Undergoing Augmentation Mammaplasty. AB - BACKGROUND: Variation in the anatomical position of the inframammary fold (IMF) in women remains poorly studied. OBJECTIVES: The purpose of this study was to evaluate the incidence of asymmetry between IMF locations on the chest wall of women undergoing breast augmentation and to determine breast measurements associated with IMF asymmetry. METHODS: Three-dimensional imaging analysis of the breasts was performed in 111 women with micromastia, using the Vectra Imaging System(TM). The following measurements were recorded: vertical distance between right and left IMF (inter-fold distance), vertical distance between nipples (inter-nipple distance), and difference between projection of right and left breasts in anterior-posterior direction. RESULTS: Asymmetry between the right and left IMF positions was found in the majority of patients (95.4%), with symmetry only found in 5 patients (4.6%). In the majority of patients (60.3%), the right IMF was located inferior to the left IMF with median inter-fold distance 0.4 cm (range, 0.1, 2.1 cm). In 39 patients (35.1%), the left IMF was located inferior to the right with median inter-fold distance 0.4 cm (range, 0.1, 1.7 cm). There was strong correlation between the degree of asymmetry of IMF and asymmetry of nipple areola complex (NAC) positions (r = 0.687, P < .01). CONCLUSIONS: The majority of women with micromastia demonstrate asymmetry of the IMF, which correlates with asymmetry of NAC location. The authors propose a classification system based on most commonly observed IMF locations as types I (right IMF inferior to left), type II (left IMF inferior to right) and type III (both IMF located on the same level). LEVEL OF EVIDENCE 4: Diagnostic. PMID- 26353800 TI - Which app should I use? PMID- 26353798 TI - Evaluating implementation of methicillin-resistant Staphylococcus aureus (MRSA) prevention guidelines in spinal cord injury centers using the PARIHS framework: a mixed methods study. AB - BACKGROUND: To prevent methicillin-resistant Staphylococcus aureus (MRSA) in Spinal Cord Injury and Disorder (SCI/D) Centers, the "Guidelines for Implementation of MRSA Prevention Initiative in the Spinal Cord Injury Centers" were released in July 2008 in the Veterans Affairs (VA) Health Care System. The purpose of this study was to use the Promoting Action on Research Implementation in Health Systems (PARiHS) framework to evaluate the experiences of implementation of SCI/D MRSA prevention guidelines in VA SCI/D Centers approximately 2-3 years after the guidelines were released. METHODS: Mixed methods were used across two phases in this study. The first phase included an anonymous, web-based cross-sectional survey administered to providers at all 24 VA SCI/D Centers. The second phase included semi-structured telephone interviews with providers at 9 SCI/D Centers. The PARiHS framework was used as the foundation of both the survey questions and semi-structured interview guide. RESULTS: The survey was completed by 295 SCI/D providers (43.8 % response rate) from 22 of the 24 SCI/D Centers (91.7 % participation rate). Respondents included nurses (57.3 %), therapists (24.4 %), physicians (11.1 %), physician assistants (3.4 %), and other health care professionals (3.8 %). Approximately 36 % of the SCI/D providers surveyed had not seen, did not remember seeing, or had never heard of the MRSA SCI/D guidelines, whereas 42.3 % of providers reported that the MRSA SCI/D guidelines were fully implemented in their SCI/D Center. Data revealed numerous barriers and facilitators to guideline implementation. Facilitators included enhanced leadership support and provider education, focused guideline dissemination to reach SCI/D providers, and strong perceived evidence supporting the guidelines. Barriers included lack of awareness of the guidelines among physical therapists and physician assistants and challenges in cohorting/isolating MRSA-positive patients and following contact precautions. CONCLUSIONS: Successful implementation of MRSA infection prevention guidelines in SCI/D settings requires (1) guideline dissemination that reaches the full range of SCI/D providers working in inpatient, outpatient, and other care settings, (2) provider education that is frequent and systematic, (3) strong leadership support, and (4) that barriers unique to the recommendations are addressed. These findings may be used to inform selection of implementation strategies and optimize infection prevention beyond MRSA as well as in other specialty care populations. PMID- 26353802 TI - Discrepant post filter ionized calcium concentrations by common blood gas analyzers in CRRT using regional citrate anticoagulation. AB - INTRODUCTION: Ionized calcium (iCa) concentration is often used in critical care and measured using blood gas analyzers at the point of care. Controlling and adjusting regional citrate anticoagulation (RCA) for continuous renal replacement therapy (CRRT) involves measuring the iCa concentration in two samples: systemic with physiological iCa concentrations and post filter samples with very low iCa concentrations. However, modern blood gas analyzers are optimized for physiological iCa concentrations which might make them less suitable for measuring low iCa in blood with a high concentration of citrate. We present results of iCa measurements from six different blood gas analyzers and the impact on clinical decisions based on the recommendations of the dialysis' device manufacturer. METHOD: The iCa concentrations of systemic and post filter samples were measured using six distinct, frequently used blood gas analyzers. We obtained iCa results of 74 systemic and 84 post filter samples from patients undergoing RCA for CRRT at the University Medicine of Greifswald. RESULTS: The systemic samples showed concordant results on all analyzers with median iCa concentrations ranging from 1.07 to 1.16 mmol/L. The medians of iCa concentrations for post filter samples ranged from 0.21 to 0.50 mmol/L. Results of >70% of the post filter samples would lead to major differences in decisions regarding citrate flow depending on the instrument used. CONCLUSION: Measurements of iCa in post filter samples may give misleading information in monitoring the RCA. Recommendations of the dialysis manufacturer need to be revised. Meanwhile, little weight should be given to post filter iCa. Reference methods for low iCa in whole blood containing citrate should be established. PMID- 26353801 TI - Effect of smoking and soft tissue release on risk of revision after total knee arthroplasty: a case- control study. AB - BACKGROUND: Increasing utilization of primary total knee arthroplasty (TKA) is projected to expand demand for revision TKA. Revision TKAs are procedurally complex and incur high costs on our financially constrained healthcare system. The purpose of this study was to use a case-control design to identify factors predisposing to revision TKA, particularly demographic, clinical and perioperative technical factors. METHODS: We conducted a case control study to investigate patient, surgical and perioperative factors associated with greater risk of revision TKA. We included patients who received TKA at a tertiary center between 1996 and 2009. Cases (patients that had primary and revision TKA) were matched to controls (patients with primary TKA that was not revised) in a 1:2 ratio and risk of revision examined using conditional logistic regression. RESULTS: We identified 146 cases and 290 controls. Patient factors independently associated with revision included male sex (OR 1.73; 95% CI 1.06-2.81) and smoking (OR 2.87; 1.33-6.19). Older age was associated with decreased risk (OR 0.83 per 5-year increment; 95% CI 0.75-0.92). Lateral release was the only technical factor associated with revision (OR 1.92; 1.07-3.43). CONCLUSIONS: In this case control study younger patient age, male gender, soft tissue release and active smoking status were associated with increased revision risk. Although we do not know whether the risk of smoking arises from short- or long-term exposure, smoking cessation prior to TKA should be considered as an intervention for decreasing revision risk. PMID- 26353803 TI - Does the importance of dietary costs for fruit and vegetable intake vary by socioeconomic position? AB - Evidence suggests that diets meeting recommendations for fruit and vegetable (F&V) intake are more costly. Dietary costs may be a greater constraint on the diet quality of people of lower socioeconomic position (SEP). The aim of this study was to examine whether dietary costs are more strongly associated with F&V intake in lower-SEP groups than in higher-SEP groups. Data on individual participants' education and income were available from a population-based, cross sectional study of 10 020 British adults. F&V intake and dietary costs (GBP/d) were derived from a semi-quantitative FFQ. Dietary cost estimates were based on UK food prices. General linear models were used to assess associations between SEP, quartiles of dietary costs and F&V intake. Effect modification of SEP gradients by dietary costs was examined with interaction terms. Analysis demonstrated that individuals with lowest quartile dietary costs, low income and low education consumed less F&V than individuals with higher dietary costs, high income and high education. Significant interaction between SEP and dietary costs indicated that the association between dietary costs and F&V intake was stronger for less-educated and lower-income groups. That is, socioeconomic differences in F&V intake were magnified among individuals who consumed lowest-cost diets. Such amplification of socioeconomic inequalities in diet among those consuming low cost diets indicates the need to address food costs in strategies to promote healthy diets. In addition, the absence of socioeconomic inequalities for individuals with high dietary costs suggests that high dietary costs can compensate for lack of other material, or psychosocial resources. PMID- 26353804 TI - Pulmonary arterial enlargement predicts cardiopulmonary complications after pulmonary resection for lung cancer: a retrospective cohort study. AB - BACKGROUND: The finding of pulmonary arterial enlargement on computed tomography has been reported to be associated with pulmonary hypertension. On the other hand, pulmonary hypertension is a known risk factor for thoracic surgery. We investigated whether pulmonary arterial enlargement predicts cardiopulmonary complications following pulmonary resection for lung cancer. METHODS: We reviewed 237 consecutive patients who underwent pulmonary resection for lung cancer. Preoperative patient characteristics (sex, age, Brinkman index, cardiopulmonary comorbidities, cardiothoracic ratio, pulmonary function, and pulmonary arterial enlargement) and surgical data (surgical procedure, pathological stage, postoperative complications, mortality, and length of postoperative hospital stay) were analyzed. In order to evaluate preoperative pulmonary arterial enlargement, we measured the diameter of the main pulmonary artery at its bifurcation and that of the ascending aorta at its widest point using chest computed tomography and calculated the ratio of the former diameter to the latter. RESULTS: In all, 16 patients developed postoperative cardiopulmonary complications and 221 did not. One patient died from postoperative pneumonia. The mean age of patients who developed postoperative cardiopulmonary complications was significantly higher than that of those who did not (78 +/- 5 years vs 69 +/- 9 years, P=0.0001). The pulmonary artery-to-ascending-aorta ratio was significantly higher in patients who developed postoperative complications than in those who did not (0.94 +/- 0.15 vs. 0.81 +/- 0.11, P=0.03). Other preoperative patient characteristics and surgical data did not differ significantly between the groups. On multivariate analysis, pulmonary artery-to ascending-aorta ratio (0.1-point increase; odds ratio 2.3, 95 % confidence interval 1.5-3.5; P=0.0002) and age (1-year increase; odds ratio 1.2, 95 % confidence interval 1.1-1.3; P=0.03) were found to be independent predictors of postoperative cardiopulmonary complications. CONCLUSIONS: A finding of pulmonary arterial enlargement on computed tomography is a potential predictor of postoperative cardiopulmonary complications after lung cancer surgery. PMID- 26353805 TI - Prooxidant activity of norbixin in model of acute gastric ulcer induced by ethanol in rats. AB - Free radicals and oxidative stress play a central role in gastric injuries caused by ethanol (EtOH). Antioxidant strategies to counteract EtOH toxicity are highly desirable. Norbixin (NBIX) is a carotenoid with antioxidant potential largely used in the food industry. This study evaluated the NBIX effects in a model of gastric ulcer induced by EtOH in rats. Male Wistar rats received NBIX doses of 0, 10, and 25 mg/kg by gavage 1 h after EtOH administration (0 or 75% solution, 1 mL/200 g of animal). The animals were euthanized 1 h after the NBIX administration, and their stomachs were removed for macroscopic and histopathological analyses, quantification of nonprotein sulfhydryl (NPSH) groups, lipid peroxidation (LPO) levels, and catalase (CAT) activity determination. NBIX increased LPO in gastric mucosa and caused CAT inhibition and NPSH depletion in EtOH-treated animals. Results showed that NBIX did not protect gastric tissue against EtOH damage, and this could be associated to a prooxidant effect. PMID- 26353807 TI - Modafinil does enhance cognition, review finds. PMID- 26353806 TI - Egg and cholesterol intake and incident type 2 diabetes among French women. AB - Egg consumption is a major source of dietary cholesterol, a nutrient that may disrupt glucose metabolism. We prospectively evaluated the relation between egg consumption and cholesterol-intake and diabetes in 65 364 French disease-free women who responded to a validated diet history questionnaire in 1993. Egg consumption included hardboiled eggs and eggs consumed in an omelette or a mixed dish, and dietary cholesterol was estimated using a French nutrient database. Over 14 years of follow-up, 1803 incident diabetes cases were identified through self-reports, supplementary questionnaires and drug reimbursement information. Multivariable Cox regression models were adjusted for age, education, menopause, menopausal hormone therapy, hypertension and hypercholesterolaemia, BMI, physical activity, smoking, alcohol, fruit, vegetables, processed red meat, coffee and sugar and artificially sweetened beverages. No association was observed between egg consumption and risk of type 2 diabetes. When comparing women who consumed at least five eggs per week with non-consumers, the multivariable hazard ratio (HR) was found to be 1.00 (95 % CI 0.78, 1.29; across categories, P trend=0.11). Women in the highest quintile of dietary cholesterol had a 40 % higher rate of diabetes compared with those in the lowest quintile (HR 1.40; 95 % CI 1.19, 1.63; across quintiles, P trend<0.0001). A 100 mg increase of dietary cholesterol per 4184 kJ (or 1000 kcal) was associated with a 14 % increase in the risk of diabetes (HR 1.14; 95 % CI 1.02, 1.26). In this large prospective cohort, we observed an association between dietary cholesterol and type 2 diabetes, but no association with egg consumption. In the absence of a clear underlying mechanism and potential residual confounding, these results should be interpreted with caution. PMID- 26353808 TI - Intraindividual changes of dipeptidyl peptidase-IV in peripheral blood of patients with rheumatoid arthritis are associated with the disease activity. AB - BACKGROUND: Dipeptidyl peptidase-IV (DPP-IV) is suggested to contribute to the pathogenesis of several autoimmune diseases. The aim of this study was to evaluate the association of DPP-IV presence in blood plasma and mononuclear cells with the disease activity in rheumatoid arthritis (RA). METHODS: Patients with active RA (n = 27) were examined at the study enrolment and a follow-up examination was performed after the regression of the joint effusions and at least 6 months after the first investigation. The control group comprised patients with a noninflammatory joint disease, i.e. osteoarthritis (OA; n = 15). The DPP-IV-like enzymatic activity was measured by a kinetic fluorimetric method, the concentration of DPP-IV in the blood plasma was determined using ELISA and the expression of DPP-IV in leukocytes was assayed by flow cytometry. RESULTS: Blood plasma DPP-IV-like enzymatic activity (median +/- SD 220.15 +/- 83.6 pkat/mL in RA vs. 376.9 +/- 144.9 pkat/mL in OA, p < 0.001) and concentrations (median +/- SD 465.1 +/- 215.6 ng/mL in RA vs. 953.3 +/- 368.4 ng/mL in OA, p < 0.001) were lower in patients with active RA compared to OA. In RA patients, the blood plasma DPP-IV-like enzymatic activity negatively correlated with the CRP concentration (r = -0.39, p = 0.044). No significant differences were observed in the DPP-IV-like enzymatic activity and DPP-IV expression in blood mononuclear cells between the RA and OA groups. At follow-up, 18 RA patients had a less active disease as demonstrated by an improved DAS28 score. In this group, comparison of the entry and the follow-up values in individual patients revealed an increase of the blood plasma DPP-IV-like enzymatic activity (median +/- SD 141 +/- 46% of the patient's entry values, p = 0.011) and DPP-IV concentration (median +/- SD 168 +/- 25%, of the patient's entry values, p = 0.033). In contrast to the blood plasma, the DPP-IV expression in blood mononuclear cells was reduced in these patients as evidenced by a decrease in the cell surface DPP IV-like enzymatic activity as well as the median fluorescence intensity of DPP-IV staining in lymphocytes (median +/- SD 66 +/- 56%, p = 0.018 and 63 +/- 31 % of the patient's entry values, p = 0.005, respectively). CONCLUSIONS: The association between RA activity and the changes in blood plasma and blood mononuclear cell DPP-IV in individual patients supports the possible relationship of DPP-IV to RA pathophysiology. PMID- 26353811 TI - A molecular framework for the identification of planthopper vectors (Hemiptera: Delphacidae) of central Argentina. AB - Planthoppers are important worldwide crop pests as well as vectors of numerous diseases. Different species transmit Mal de Rio Cuarto virus, which causes the most economically important corn disease in central Argentina. Epidemiological studies rely on the accurate identification of the species present in the field. Presently, morphological identification of planthoppers requires taxonomic expertise and there are no taxonomic keys for females and nymphs. Nevertheless, no molecular protocols are available for accurate species identification of most frequent delphacid species from central Argentina. In this context, the aim of this study was to evaluate the utility of the cytochrome oxidase I gene (COI) as a DNA barcode and its digestion with restriction enzymes (Restriction Fragment Length Polymorphism, RFLP) for the identification of the most common species of planthoppers in central Argentina. We amplified and sequenced a 843 bp fragment of the COI gene of taxonomically identified specimens and evaluated its use as a DNA barcode. Restriction enzymes were also selected for digesting the COI fragment via RFLP. The high interspecific variability (20.79%; +/- 2.32%) and low intraspecific divergence (0.12%; +/- 0.17%) observed in the studied species, demonstrate the effectiveness of the COI gene for species identification of major vector delphacids affecting corn crops in Argentina. Moreover, the digestion of this COI gene fragment with Bfa I and Apo I enzymes allows a fast and cost effective species identification method when numerous specimens need to be processed. Both molecular techniques developed here, allow the accurate identification of planthopper species at regional scale. These new tools would assist traditional identification of these insects, especially for aiding non experts in morphological taxonomy. PMID- 26353810 TI - Acquired Gerbode defect following endocarditis of the tricuspid valve: a case report and literature review. AB - The Gerbode's defect is a communication between the left ventricle and right atrium. It is usually congenital, but rarely is acquired, as a complication of endocarditis, myocardial infarction, trauma, or after previous cardiac surgery. The acquired Gerbode defect with involvement of the tricuspid valve acquired after bacterial endocarditis can be challenging to repair. We present a rare case of young woman, with endocarditis of the tricuspid valve and acquired Gerbode defect without previous cardiac surgery. She underwent successful surgical closure of the Gerbode defect and reconstruction of the septal leaflet of the tricuspid valve using a an autologous pericardial patch. A total of 20 other cases were reported with acquired Gerbode defect due to endocarditis in patients without previous cardiac surgery. Three other cases presented acquired Gerbode defect due to myocardial infarction and two due to chest trauma. Another series of 62 patients presented acquired Gerbode defect after previous cardiac surgery. Surgical treatment is always feasible with excellent outcome. However the percutanous transcatheter closure remains an excellent option especially in high risk patients. PMID- 26353812 TI - Is lactate clearance impaired in septic shock? PMID- 26353809 TI - Subsequent shock deliveries are associated with increased favorable neurological outcomes in cardiac arrest patients who had initially non-shockable rhythms. AB - INTRODUCTION: Previous studies evaluating whether subsequent conversion to shockable rhythms in patients who had initially non-shockable rhythms was associated with altered clinical outcome reported inconsistent results. Therefore, we hypothesized that subsequent shock delivery by emergency medical service (EMS) providers altered clinical outcomes in patients with initially non shockable rhythms. METHODS: We tested for an association between subsequent shock delivery in EMS resuscitation and clinical outcomes in patients with initially non-shockable rhythms (n = 11,481) through a survey of patients after out-of hospital cardiac arrest in the Kanto region (SOS-KANTO) 2012 study cohort, Japan. The primary investigated outcome was 1-month survival with favorable neurological functions. The secondary outcome variable was the presence of subsequent shock delivery. We further evaluated the association of interval from initiation of cardiopulmonary resuscitation to shock with clinical outcomes. RESULTS: In the univariate analysis of initially non-shockable rhythms, patients who received subsequent shock delivery had significantly increased frequency of return of spontaneous circulation, 24-hour survival, 1-month survival, and favorable neurological outcomes compared to the subsequent not shocked group (P < 0.0001). In the multivariate logistic regression analysis, subsequent shock was significantly associated with favorable neurological outcomes (vs. not shocked; adjusted P = 0.0020, odds ratio, 2.78; 95% confidence interval, 1.45-5.30). Younger age, witnessed arrest, initial pulseless electrical activity rhythms, and cardiac etiology were significantly associated with the presence of subsequent shock in patients with initially non-shockable rhythms. CONCLUSIONS: In this study of cardiac arrest patients with initially non-shockable rhythms, patients who received early defibrillation by EMS providers had increased 1-month favorable neurological outcomes. PMID- 26353813 TI - An ex-vivo quantitative assessment to determine the optimal aortotomy closure technique. AB - BACKGROUND: After performing an aortotomy, there are a variety of techniques utilized for suture closure. There is no published data comparing the efficacy of various suture techniques. The goal of this study is to provide an ex-vivo quantitative assessment of resistance to leakage and dehiscence for three aortotomy closure techniques. MATERIALS AND METHODS: An ex-vivo model was developed utilizing explanted porcine aorta. Aortotomies were closed using one of three techniques: 1) single layer baseball stitch 2) double layer baseball stitch 3) horizontal mattress stitch with a top layer baseball stitch. The aorta was pressurized with saline using an apparatus which captured all leaked fluid. The intra-aortic pressure was adjusted over 8 increments from 110 to 375 mmHg. Leakage rates were determined at each pressure level. Ten aortotomies were performed for each technique, resulting in 240 calculated leakage rates. RESULTS: At all pressures, the horizontal mattress group was measured to have significantly less leakage when compared to single or double layer baseball stitch closures (p < 0.005). There was a trend towards a lower leakage rate in the double layer baseball compared to the single layer baseball stitch. However, this difference is statistically significant only at 300 and 335 mmHg. There were no instances of rupture. CONCLUSION: This study provides the first quantitative comparison of three commonly used aortotomy closure techniques. The running horizontal mattress stitch combined with a baseball stitch provides the greatest resistance to leakage at all pressures. This technique may be superior in clinical scenarios with challenging hemostasis. PMID- 26353814 TI - Recurrence of post burn contractures of the elbow and shoulder joints: experience from a Ugandan hospital. AB - BACKGROUND: Recurrence of post-burn contractures, following inadequate management of post-burn contractures (PBC), is under reported. It is associated with multiple operations and an increased cost to patients and their families. The purpose of this study was to determine the frequency of recurrence of PBC of the shoulder and the elbow joint three months after surgical intervention and the associated risk- factors. METHODS: This was a prospective cohort study conducted at CoRSU hospital from March 2012 to November 2014. All patients with PBC of the elbow and/or shoulder joint who consented to be in the study and met the inclusion criteria were enrolled. Data was collected using a pretested, coded questionnaire. A goniometer was used to measure the active range of motion of the involved joint. The measurements were recorded in degrees. The data was analysed with STATA version 12.1. RESULTS: 58 patients were enrolled consecutively in the study. There were 36 females and 22 males, with a female to male ratio of 1.6:1. The age range was 0.75-45 years, with a median age of 5 years. The average age at the time of injury was 3.4 years. The most common cause of initial burn injury was scalding. The average number of joints involved per patient was two. There was a high incidence of recurrence of PBC (52 %) among the participants. The shoulder had the highest frequency of recurrence at 67 %. The elbow joint had a frequency of recurrence of 27 %. All participants with both elbow and shoulder joint involvement had PBC recur. The risk factors for recurrence were flame burn (p = 0.007), duration of PBC of more than 1 year (p = 0.018), and incomplete release of the contracture (p = 0.002). The presence of keloids, hypertrophic scars, ulcers and the occurrence of complications at the contracture site were not associated with recurrence of PBC. CONCLUSION: Recurrence of PBC of the elbow and shoulder joint is a common problem. The risk factors should be kept in mind during management of PBC to reduce the recurrence rate. PMID- 26353815 TI - A low-cost alternative for nasolaryngoscopy simulation training equipment: a randomised controlled trial. AB - OBJECTIVES: Flexible nasolaryngoscopy is a key diagnostic procedure used in many specialities. Simulation-based teaching is beneficial for endoscopy training, but it is expensive. This study assessed whether an inexpensive simulation model is an effective training method for flexible nasolaryngoscopy. METHODS: A three armed, randomised, controlled trial was performed. One group received no simulation training, while two others were trained with either a high-cost or a low-cost model. All candidates then performed flexible nasolaryngoscopy on a volunteer. Their ability to perform this task was assessed by the patient discomfort score and time taken by a blinded expert. RESULTS: Simulation-based teaching reduced patient discomfort and improved candidate skill level. Low-cost model training did not have a negative effect when compared with high-cost model training. CONCLUSION: Simulated flexible nasolaryngoscopy training may be more accessible with the use of an effective low-cost model. PMID- 26353817 TI - Successful surgical management of a rare esophageal inflammatory myofibroblastic tumour: a case report. AB - Inflammatory myofibroblastic tumour (IMT) is an uncommon mesenchymal tumour, which can occur anywhere in the body, rarely in esophagus. Mostly, the diagnosis is postoperative, after the hispathological evaluation of the specimen. There are no definite guidelines regarding the diagnosis and management. Here, we report a 60 year old lady presenting with dysphagia, diagnosed to have a submucosal esophageal tumor with Barium esophagogram and contrast enhanced computed tomography. She was managed successfully with surgical enucleation with the final histopathological diagnosis of IMT. Surgical excision is not only therapeutic but also diagnostic in such cases. PMID- 26353816 TI - Small-scale gene duplications played a major role in the recent evolution of wheat chromosome 3B. AB - BACKGROUND: Bread wheat is not only an important crop, but its large (17 Gb), highly repetitive, and hexaploid genome makes it a good model to study the organization and evolution of complex genomes. Recently, we produced a high quality reference sequence of wheat chromosome 3B (774 Mb), which provides an excellent opportunity to study the evolutionary dynamics of a large and polyploid genome, specifically the impact of single gene duplications. RESULTS: We find that 27 % of the 3B predicted genes are non-syntenic with the orthologous chromosomes of Brachypodium distachyon, Oryza sativa, and Sorghum bicolor, whereas, by applying the same criteria, non-syntenic genes represent on average only 10 % of the predicted genes in these three model grasses. These non-syntenic genes on 3B have high sequence similarity to at least one other gene in the wheat genome, indicating that hexaploid wheat has undergone massive small-scale interchromosomal gene duplications compared to other grasses. Insertions of non syntenic genes occurred at a similar rate along the chromosome, but these genes tend to be retained at a higher frequency in the distal, recombinogenic regions. The ratio of non-synonymous to synonymous substitution rates showed a more relaxed selection pressure for non-syntenic genes compared to syntenic genes, and gene ontology analysis indicated that non-syntenic genes may be enriched in functions involved in disease resistance. CONCLUSION: Our results highlight the major impact of single gene duplications on the wheat gene complement and confirm the accelerated evolution of the Triticeae lineage among grasses. PMID- 26353818 TI - The effects of cannabis on memory function in users with and without a psychotic disorder: findings from a combined meta-analysis. AB - BACKGROUND: Effect of cannabis use on memory function is a contentious issue, with effects being different in healthy individuals and patients with psychosis. METHOD: Employing a meta-analytic approach we investigated the effects of cannabis use on memory function in patients with psychosis and healthy individuals, and the effect of diagnosis, memory dimension and moderating factors. A total of 88 studies were identified through a systematic literature search, investigating healthy (n = 7697) and psychotic (n = 3261) individuals. Standardized mean differences between the cannabis user and non-user groups on memory tasks were estimated using random-effects models and the effect-size statistic Cohen's d. Effects of potential moderating factors were tested using mixed-effects models and subgroup analyses. RESULTS: We found that cannabis use was associated with significantly (p ? 0.05) impaired global (d = 0.27) and prospective memory (d = 0.61), verbal immediate (d = 0.40) and delayed (d = 0.36) recall as well as visual recognition (d = 0.41) in healthy individuals, but a better global memory (d = -0.11), visual immediate recall (d = -0.73) and recognition (d = -0.42) in patients. Lower depression scores and younger age appeared to attenuate the effects of cannabis on memory. Cannabis-using patients had lower levels of depression and were younger compared with non-using patients, whilst healthy cannabis-users had higher depression scores than age-matched non users. Longer duration of abstinence from cannabis reduced the effects on memory in healthy and patient users. CONCLUSIONS: These results suggest that cannabis use is associated with a significant domain-specific impairment in memory in healthy individuals but not in cannabis-using patients, suggesting that they may represent a less developmentally impaired subgroup of psychotic patients. PMID- 26353819 TI - Translational approaches to functional platelet production ex vivo. AB - Platelets, which are released by megakaryocytes, play key roles in haemostasis, angiogenesis, immunity, tissue regeneration and wound healing. The scarcity of clinical cures for life threatening platelet diseases is in a large part due to limited insight into the mechanisms that control the developmental process of megakaryocytes and the mechanisms that govern the production of platelets within the bone marrow. To overcome these limitations, functional human tissue models have been developed and studied to extrapolate ex vivo outcomes for new insight on bone marrow functions in vivo. There are many challenges that these models must overcome, from faithfully mimicking the physiological composition and functions of bone marrow, to the collection of the platelets generated and validation of their viability and function for human use. The overall goal is to identify innovative instruments to study mechanisms of platelet release, diseases related to platelet production and new therapeutic targets starting from human progenitor cells. PMID- 26353821 TI - Prevalence and Correlates of Lower-Extremity Amputation in Patients With Diabetic Foot Ulcer in Jeddah, Saudi Arabia. AB - This cross-sectional study investigated the prevalence and correlates of lower extremity amputation (LEA) in a Saudi population with diabetic foot ulcer. The study population consisted of 91 participants, with a median age of 55.0 years. Biomarkers were measured following standard protocols. Local symptoms of foot ulcer, including peripheral neuropathy (PN), peripheral artery disease (PAD), and foot infection were diagnosed by standard objective diagnostic tools or diagnosed clinically by a specialized surgeon. The severity of foot ulcer was classified according to the Wagner wound classification system. The prevalence of LEA was 29.7% in this population. The odds ratio for LEA comparing extreme tertiles was 2.42 (95% confidence interval [CI] = 0.70-8.45; P for trend = .03) for ulcer size and 0.22 (95% CI = 0.06-0.87; P for trend = .03) for high-density lipoprotein cholesterol. C-reactive protein and homocysteine levels were each positively associated with odds of LEA, but the associations became nonsignificant in multivariable models. Participants with foot infection showed a significantly higher adjusted prevalence of LEA (40.7%, 95% CI = 27.1%-54.3%) compared with those without foot infections (19.3%, 95% CI = 6.0%-32.4%, P = .03). Participants with Wagner grade >=3 presented a significantly higher prevalence (40.5%, 95% CI = 27.8%-53.2%) than those with Wagner grade of 1 or 2 (16.4%, 95% CI = 2.4% 30.5%, P = .02). Participants with PN and PAD showed nonsignificantly higher prevalence of LEA. We found a relatively high prevalence of LEA as well as several clinical markers and local symptoms associated with LEA in this Saudi population with diabetic foot ulcer. PMID- 26353820 TI - Geographic patterns in patient demographics and insulin use in 18 countries, a global perspective from the multinational observational study assessing insulin use: understanding the challenges associated with progression of therapy (MOSAIc). AB - BACKGROUND: Among patients with type 2 diabetes, insulin intensification to achieve glycemic targets occurs less often than clinically indicated. Barriers to intensification are not well understood. We present patients' baseline characteristics from MOSAIc, a study investigating patient-, physician-, and healthcare environment-based factors affecting insulin intensification and subsequent health outcomes. METHODS: MOSAIc is a longitudinal, observational study following patients' diabetes care in 18 countries: United Arab Emirates (UAE), Argentina, Brazil, Canada, China, Germany, India, Israel, Italy, Japan, Mexico, Russia, Saudi Arabia, South Korea, Spain, Turkey, United Kingdom, United States. Eligible patients are age >= 18, have type 2 diabetes, and have used insulin for >= 3 months with/without other antidiabetic medications. Extensive baseline demographic, clinical, and psychosocial data are collected at baseline and regular intervals during the 24-month follow-up. We conducted descriptive analyses of baseline data. RESULTS: Four thousand three hundred forty one patients met eligibility criteria. Patients received their type 2 diabetes diagnosis 12 +/- 8 years prior to baseline visit, yet patients in developing countries were younger than in developed countries (e.g., UAE, 55 +/- 10; Germany = 70 +/- 10). Saudi Arabians had the highest HbA1c values (9.0 +/- 2.2) and Germany (7.5 +/- 1.4) among the lowest. Most patients in 5 (28%) of the 18 countries did not use an oral antidiabetic drug. Over half of patients in fourteen (78 %) countries exclusively used basal insulin; most Indian and Chinese patients exclusively used mixed insulin. CONCLUSIONS: MOSAIc's baseline data highlight differences in patient characteristics across countries. These patterns, along with physician and healthcare environment differences, may contribute to the likelihood of insulin intensification and subsequent clinical outcomes. PMID- 26353822 TI - Novel Use of Synthetic Acellular Dermal Matrix for Coverage of a Tibial Defect Following Resection of an Osteochondroma: A Case Report. AB - The application of an artificial dermal matrix (Integra Life Sciences, Plainsboro, NJ) in the management of substantial burn injuries has been extensively documented. Use of an artificial dermal matrix has resulted in excellent outcomes and is free of the morbidity associated with harvesting free tissue flaps. However, coverage of bony defects where the periosteum has been removed is often challenging. In the current report, we present a case wherein the use of an acellular synthetic dermis combined with split-thickness skin grafting resulted in successful coverage of a tibial defect following resection of an osteochondroma. PMID- 26353823 TI - Risk Factors for Chronic Intertrigo of the Lymphedema Leg in Southern India: A Case-Control Study. AB - Rich clinical experiences indicate that toe web intertrigo is a major predisposing condition for cellulitis/acute dermatolymphango adenitis (ADLA) and the number of lesions is the strongest predictor of frequency of ADLA in lymphedema (LE) patients. However, there is scanty information on the risk factors for the establishment of chronic toe web intertrigo in LE patients. We performed a case-control study recruiting 52 lower limb LE with intertrigo and 52 lower limb LE without intertrigo in community settings and assessed general and local potential risk factors for chronic intertrigo. Analysis of local risk factors revealed that topical application of oil, tingling and numbness of the extremities were associated independently with chronic intertrigo. In multivariate analysis, LE grades III and IV were associated with chronic intertrigo, after adjusting for tingling and numbness, prophylactic antibiotic, age group, and gender. From a public health perspective, LE patients of grades III and IV and patients under antibiotic prophylaxis should be self-motivated to look for the early symptoms of toe web intertrigo to prevent chronic stage and recurrent episodes of cellulitis. Patients with history of tingling and numbness of the periphery need to be monitored for pressure effects leading to poor vascularization and delayed healing of intertrigo. PMID- 26353824 TI - Lower Extremity Wounds in Patients With Idiopathic Thrombocytopenic Purpura and Systemic Lupus Erythematosus. AB - Infections in lower extremities are sometimes concerned with systemic immunological disorders such as idiopathic thrombocytopenic purpura and systemic lupus erythematosus, which are treated with systemic steroids. Steroid therapy impairs the epithelial wound healing and with systemic condition, especially with systemic lupus erythematosus, the wound is susceptible for infection. Even a pyoderma gangrenosum sometimes occurs in a patient with idiopathic thrombocytopenic purpura with an incisional wound of hernia. The severe signs and symptoms are the deep skin and soft tissue infections, mainly caused by group A streptococcus, composed of necrotizing fasciitis and muscle necrosis. Medically suspected necrotizing fasciitis patients should be empirically and immediately administered with broad-spectrum antibiotics, which may cover the common suspected pathogens. In type I (polymicrobial) infection, the selection of antimicrobial should be based on medical history and Gram staining and culture. The coverage against anaerobes is important in type I infection. Metronidazole, clindamycin, or beta-lactams with beta-lactamase inhibitor or carbapenems are the treatment of choice against anaerobes, while early surgical debridement-wide enough and deep enough-is the core treatment of necrotizing fasciitis and results in significantly better mortality compared with those who underwent surgery after a few hours of delay. When necrotizing fasciitis is considered and the patient is brought to the operation room, aggressive and extensive surgical debridement is explored. Tissue involved should be completely removed until no further evidence of infection is seen. When further debridement is required, the patient must return to the operating room immediately. In this context, the temporal coverage using the artificial dermis after debridement is useful because there is no loss of the patient's own tissue and yet it is easier for "second-look" surgery or secondary reconstruction, and extensive enough debridement is always the mainstay of the therapy. PMID- 26353825 TI - The effectiveness of VIPP-V parenting training for parents of young children with a visual or visual-and-intellectual disability: study protocol of a multicenter randomized controlled trial. AB - BACKGROUND: Visual or visual-and-intellectual disabilities of children make daily interactions more difficult for their parents and may impact the quality of the parent-child relationship. To support these parents, an existing intervention (Video-feedback Intervention to promote Positive Parenting; VIPP; Juffer F, Bakermans-Kranenburg MJ, van IJzendoorn MH, 2008. Promoting positive parenting; an attachment-based intervention. Mahwah, NJ: Lawrence Erlbaum Associates; 2008) was adapted for use with parents of children with a visual or visual-and intellectual disability (VIPP-V). This attachment-based intervention was hypothesized to support parents' interpretation and understanding of the behavior of their child with a visual or visual-and-intellectual disability and respond to their child's signals in a sensitive way to improve parent-child interaction quality. METHODS/DESIGN: A randomized controlled trial (RCT) will be conducted to assess the effectiveness of the adapted intervention VIPP-V (Video-feedback Intervention to promote Positive Parenting in parents of children with Visual or visual-and-intellectual disabilities). Parent-child dyads will be randomized into two groups: 50 dyads will receive VIPP-V in combination with care-as-usual and 50 dyads will receive care-as-usual. Families with a child (1-5 years of age) with a visual or visual-and-intellectual disability will be recruited for participation in the study. Primary outcome measures are parental sensitivity and the quality of parent-child interaction. Secondary outcome measures are parental self efficacy, and parenting stress. To assess feasibility of implementation of the intervention the experiences of early intervention workers with regard to using VIPP-V are assessed. Moderator variables are the child's developmental age, working alliance between parent and VIPP-V intervention worker and empathy of the VIPP-V intervention worker. Data will be collected approximately one week before the intervention starts (T1), one week (T2) and three months (T3) after the intervention. Parent-child dyads in the care-as-usual-only condition will be assessed at the same time points. Both intention-to-treat and completer analyses will be performed. DISCUSSION: Descriptive findings in pilot cases suggest benefits from VIPP-V, and compatibility with existing services for parents of children with a visual or visual-and-intellectual disability. The current study will provide insight into the effectiveness of this intervention for parents of children with a visual or visual-and-intellectual disability, and, if the intervention is effective, prepare the field for broad-scale implementation. TRIAL REGISTRATION: Nederlands Trial Register NTR4306 (registered 5 December 2013). PMID- 26353826 TI - [Severe complications after non-intended usage of octenidine dihydrochloride. A case series with four dogs]. AB - OBJECTIVE: Case series of four dogs in which extensive bite wounds had been treated using octenidine dihydrochloride (Octenivet(r) or Octenisept(r)) flushing. The dogs subsequently developed severe local complications. MATERIAL AND METHODS: Retrospective evaluation of clinical symptoms, diagnostics, therapy and course of the disease. RESULTS: In four dogs, severe necrosis and persistent edematous changes of the treated area developed after the application of octenidine dihydrochloride. The clinical course was comparable to complications described previously in human medicine. Therapy was protracted and complicated by secondary wound infection. CONCLUSION AND CLINICAL RELEVANCE: Irrigation of deep wounds, particularly bite wounds, using octenidine dihydrochloride without drainage may lead to persistent edematous changes, inflammatory reactions and necrosis. The inappropriate application of octenidine dihydrochloride for wound irrigation should be avoided in veterinary medicine. PMID- 26353827 TI - Lactation and digestion in dairy cows fed ensiled total mixed ration containing steam-flaked or ground rice grain. AB - The objective of this experiment was to investigate the effect of feeding ensiled total mixed ration (TMR) containing steam-flaked (SF) or ground brown rice (Oryza satira L.; BR) on feed intake, lactation performance, digestion, ruminal fermentation and nitrogen (N) utilization in dairy cows. Eight multiparous Holstein cows were used in a crossover design with two dietary treatments: diets containing either SF or fine ground (FG) BR at 24% of dietary dry matter. Dietary treatment did not affect dry matter intake or milk yield and composition. The whole-tract digestibility of organic matter and fiber decreased, and the digestibility of starch increased with the replacement of SF with FG in ensiled TMR, but these differences were small between diets. Crude protein digestibility was not different between diets. The processing method of BR did not affect ruminal pH, total volatile acid concentration, or volatile fatty acid proportion in cows. The N intake, milk N secretion, fecal and urinary N excretion and N retention were not influenced by dietary treatment. These results show that feeding ensiled TMR containing FG instead of SF reduces fiber digestibility but has little impact on lactation and N utilization when diets contained 24% on a dry matter basis. PMID- 26353828 TI - ISPRM discussion paper: proposing dimensions for an International Classification System for Service Organization in Health-related Rehabilitation. AB - OBJECTIVE: Rehabilitation is 1 of 4 main health strategies. The World Report on Disability identifies deficits in rehabilitation care for people with disabilities as an important barrier to full inclusion in society or to achieve optimal functioning. In order to overcome such deficits, to close gaps in national and/or regional rehabilitation systems, and to develop appropriate rehabilitation services, it is crucial to define uniform criteria and a widely accepted language to describe and classify rehabilitation services. The aim of this paper was therefore to develop a list of dimensions and categories to describe the organization of health-related rehabilitation services. METHODS: The classification is based on a series of expert workshops including members of the International and European Society of Physical Medicine and Rehabilitation. RESULTS: The proposed classification has 2 levels (dimensions and categories). The upper level distinguishes 3 dimensions: the service provider (with 9 categories), the funding of the service (with 3 categories), and the service delivery (8 subcategories). A further specification of the categories in a 3 level classification (including value sets) is needed. CONCLUSION: This paper is an intermediate step towards development of a classification system with distinct categories and dimensions. PMID- 26353830 TI - Positive association between serious psychiatric outcomes and complications of diabetes mellitus in patients with depressive disorders. AB - OBJECTIVES: Depression and diabetes are closely biologically and behaviorally intertwined. We examined the impact of comorbid diabetes mellitus on the incidence of serious psychiatric outcomes among patients with depression. METHODS: We used claims data from the Korean Health Insurance Review & Assessment Service database of patients who were diagnosed with depression within one year of an index prescription for antidepressants between January 2007 and June 2008. We investigated the association between the comorbidity of diabetes mellitus and serious psychiatric outcomes of depression, such as psychiatric hospitalization, psychiatric emergency room visits, and suicide attempts. RESULTS: Among 200,936 patients with depression, 74,160 (36.9%) had diabetes mellitus, including 57,418 (28.6%) with complications. The incidence of serious psychiatric outcomes was 3.3% in patients with depression without diabetes and 6.7% in patients with depression and diabetes mellitus. Patients with depression and diabetes mellitus complications showed higher rates of serious outcomes than that did those without diabetes mellitus complications (odds ratio, 1.19; 95% confidence interval, 1.11 1.13). Similarly, depressed patients with micro and macrovascular diabetic complications were more likely to experience serious outcomes than those without diabetes mellitus complications (odds ratio, 2.2; 95% confidence interval, 2.07 2.34). CONCLUSIONS: Our results showed that comorbid diabetes mellitus can increase the risk of serious outcomes of depression, such as suicide and hospitalization, and thus may alter the antidepressants prescription patterns and healthcare service use among patients with depressive disorders. PMID- 26353829 TI - Prevention of vitamin D deficiency in children following cardiac surgery: study protocol for a randomized controlled trial. AB - BACKGROUND: Vitamin D is a pleiotropic hormone important for the recovery of organ systems after critical illness. Recent observational studies have suggested that three out of every four children are vitamin D deficient following cardiac surgery, with inadequate preoperative intake and surgical losses playing important contributory roles. Observed associations between postoperative levels, cardiovascular dysfunction and clinical course suggest that perioperative optimization of vitamin D status could improve outcome. With this two-arm, parallel, double blind, randomized controlled trial (RCT), we aim to compare immediate postoperative vitamin D status in children requiring cardiopulmonary bypass for congenital heart disease who receive preoperative daily high dose vitamin D supplementation (high-dose arm) with those who receive usual intake (low-dose arm). METHODS/DESIGN: Eligibility requirements include age (>36 weeks, <18 years) and a congenital heart defect requiring cardiopulmonary bypass surgical correction. Enrollment of 62 participants will take place at a single Canadian tertiary care center over a period of 2 years. Children randomized to the high-dose group will receive age-based dosing that was informed by the Institute of Medicine (IOM) daily tolerable upper intake level (<1 year old = 1,600 IU/day, >1 year old = 2,400 IU/day). Children in the low-dose arm will receive usual care based on IOM recommendations (<1 year old = 400 IU, >1 year old = 600 IU). The primary outcome measure is immediate postoperative vitamin D status, using blood 25(OH)D. DISCUSSION: Maintaining adequate postoperative vitamin D levels following surgery could represent an effective therapy to speed recovery following CHD surgery. The proposed research project will determine whether preoperative supplementation with a dosing regimen based on the IOM recommended daily upper tolerable intake will prevent postoperative vitamin-D deficiency in the majority of children. The results will then be used to inform the design of a large international RCT exploring whether preoperative optimization of vitamin D status might improve short and long-term outcomes in this vulnerable population. TRIAL REGISTRATION: Clinicaltrials.gov Identifier- NCT01838447 Date of registration: 11 April 2013. PMID- 26353831 TI - Responsiveness to sensory cues using the Timed Up and Go test in patients with Parkinson's disease: a prospective cohort study. AB - OBJECTIVE: To test the effectiveness of the Timed Up and Go (TUG) test to define responsiveness to auditory and visual cues in patients with Parkinson's disease. METHODS: Consecutive patients > 50 years old were enrolled if they were classified as stage 1-3 of the Hoehn and Yahr scale; scored <= 45 on part III of the Unified Parkinson's Disease Rating Scale; > 23 on the Mini-Mental State Examination; and were able to perform the TUG test without assistance. Within subject analysis identified positive-responders, negative-responders and non responders. TUG times with and without sensory cues were studied among all patients, and among responders only using the Friedman Test. RESULTS: Twenty-two patients (16 men, 6 women), mean age 72.4 years (standard deviation (SD) 8.7 years) were included. Basal mean TUG time was 12.3 (SD 4.0). TUG times after visual cues (11.7 (SD 4.8)) were lower than in basal conditions (p = 0.006), whereas TUG times after auditory cues were not (p > 0.05). In the 16 patients who were positive-responders, mean TUG times after visual (11.0 (SD 3.1)) and auditory (11.3 (SD 3.6)) cues were lower than in basal conditions (12.5 (SD 3.8)) (p = 0.0002). CONCLUSION: The TUG test may be used to tailor the rehabilitation programme in patients with Parkinson's disease, identifying those who respond to visual and auditory cueing. PMID- 26353832 TI - Effectiveness of a night positioning programme on ankle range of motion in patients after hemiparesis: a prospective randomized controlled pilot study. AB - OBJECTIVE: To investigate the effect of night positioning on ankle motion in patients after stroke or brain injury. DESIGN: Prospective randomized controlled pilot study with 3 groups: bivalve cast; pressure-relieving ankle-foot orthosis; and control. SUBJECTS/PATIENTS: Adults (n = 46) in inpatient rehabilitation with lower extremity paresis following stroke or brain injury. METHODS: Intervention group participants wore a custom bivalve cast or pre-fabricated orthosis 8-12 h/night. The primary outcome variable was passive ankle dorsiflexion. Muscle spasticity (Modified Ashworth Scale) and functional mobility (Functional Independence Measure) were also assessed. RESULTS: No significant differences were found between groups for all outcome measures at the pilot sample size (p > 0.05). Control and pressure-relieving ankle-foot orthosis groups showed improvement in ankle dorsiflexion, and the bivalve cast group demonstrated a trend toward decreased spasticity. Positioning interventions were tolerated for approximately 11 h/night. Baseline range of motion was measured and a retrospective power analysis determined that a sample size of 234 is needed for 80% power to establish significance. CONCLUSION: Future research with a larger sample size is re-commended to determine significance and whether a more specific subset of patients would benefit from night positioning to maximize treatment time during daytime therapy sessions. PMID- 26353834 TI - [The new Anti-Corruption Act: How will physicians be affected?]. PMID- 26353833 TI - Certolizumab pegol plus methotrexate 5-year results from the rheumatoid arthritis prevention of structural damage (RAPID) 2 randomized controlled trial and long term extension in rheumatoid arthritis patients. AB - INTRODUCTION: As patients with rheumatoid arthritis (RA) receive treatment with anti-tumour necrosis factors over several years, it is important to evaluate their long-term safety and efficacy. The objective of this study was to examine the safety and benefits of certolizumab pegol (CZP)+methotrexate (MTX) treatment for almost 5 years in patients with RA. METHODS: Patients who completed the 24 week Rheumatoid Arthritis Prevention of Structural Damage (RAPID) 2 randomized controlled trial (RCT; NCT00160602), or who were American College of Rheumatology (ACR) 20 non-responders at Week 16, entered the open-label extension (OLE; NCT00160641). After >=6 months treatment with CZP 400 mg every two weeks (Q2W), dose was reduced to 200 mg Q2W, the approved maintenance dose. Safety data are presented from all patients who received >=1 dose CZP (Safety population, n=612). Efficacy data are presented to Week 232 for the intent-to-treat (ITT, n=492) and Week 24 CZP RCT Completer (n=342) populations, and through 192 weeks of dose reduction for the Dose-reduction population (patients whose CZP dose was reduced to 200 mg, n=369). Radiographic progression (modified total Sharp score change from RCT baseline >0.5) to Week 128 is reported for the Week 24 CZP Completers. RESULTS: In the RCT, 619 patients were randomized to CZP+MTX (n=492) or placebo+MTX (n=127). Overall, 567 patients (91.6%) entered the OLE: 447 CZP and 120 placebo patients. Of all randomized patients, 358 (57.8%) were ongoing at Week 232. Annual drop-out rates during the first four years ranged from 8.4 15.0%. Event rates per 100 patient-years were 163.0 for adverse events (AEs) and 15.7 for serious AEs. Nineteen patients (3.1%) had fatal AEs (incidence rate=0.8). Clinical improvements in the RCT were maintained to Week 232 in the CZP Completers: mean Disease Activity Score 28 (Erythrocyte Sedimentation Rate) change from baseline was -3.4 and ACR20/50/70 responses 68.4%/47.1%/25.1% (non responder imputation). Similar improvements observed in the ITT were maintained following dose-reduction. 73.2% of CZP Completers had no radiographic progression at Week 128. CONCLUSIONS: In patients with active RA despite MTX therapy, CZP was well tolerated, with no new safety signals identified. CZP provided sustained improvements in clinical outcomes for almost 5 years. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00160602 and NCT00160641 . Registered 8 September 2005. PMID- 26353835 TI - An exploratory analysis of the nature of informal knowledge underlying theories of planned action used for public health oriented knowledge translation. AB - BACKGROUND: Informal knowledge is used in public health practice to make sense of research findings. Although knowledge translation theories highlight the importance of informal knowledge, it is not clear to what extent the same literature provides guidance in terms of how to use it in practice. The objective of this study was to address this gap by exploring what planned action theories suggest in terms of using three types of informal knowledge: local, experiential and expert. We carried out an exploratory secondary analysis of the planned action theories that informed the development of a popular knowledge translation theory. Our sample included twenty-nine (n = 29) papers. We extracted information from these papers about sources of and guidance for using informal knowledge, and then carried out a thematic analysis. RESULTS: We found that theories of planned action provide guidance (including sources of, methods for identifying, and suggestions for use) for using local, experiential and expert knowledge. CONCLUSION: This study builds on previous knowledge translation related work to provide insight into the practical use of informal knowledge. Public health practitioners can refer to the guidance summarized in this paper to inform their decision-making. Further research about how to use informal knowledge in public health practice is needed given the value being accorded to using informal knowledge in public health decision-making processes. PMID- 26353836 TI - Nocturnal "humming" vocalizations: adding a piece to the puzzle of giraffe vocal communication. AB - BACKGROUND: Recent research reveals that giraffes (Giraffa camelopardalis sp.) exhibit a socially structured, fission-fusion system. In other species possessing this kind of society, information exchange is important and vocal communication is usually well developed. But is this true for giraffes? Giraffes are known to produce sounds, but there is no evidence that they use vocalizations for communication. Reports on giraffe vocalizations are mainly anecdotal and the missing acoustic descriptions make it difficult to establish a call nomenclature. Despite inconclusive evidence to date, it is widely assumed that giraffes produce infrasonic vocalizations similar to elephants. In order to initiate a more detailed investigation of the vocal communication in giraffes, we collected data of captive individuals during day and night. We particularly focussed on detecting tonal, infrasonic or sustained vocalizations. FINDINGS: We collected over 947 h of audio material in three European zoos and quantified the spectral and temporal components of acoustic signals to obtain an accurate set of acoustic parameters. Besides the known burst, snorts and grunts, we detected harmonic, sustained and frequency-modulated "humming" vocalizations during night recordings. None of the recorded vocalizations were within the infrasonic range. CONCLUSIONS: These results show that giraffes do produce vocalizations, which, based on their acoustic structure, might have the potential to function as communicative signals to convey information about the physical and motivational attributes of the caller. The data further reveal that the assumption of infrasonic communication in giraffes needs to be considered with caution and requires further investigations in future studies. PMID- 26353837 TI - Prognostic role of PIK3CA mutations of cell-free DNA in early-stage triple negative breast cancer. AB - PIK3CA is an oncogene that encodes the p110alpha component of phosphatidylinositol 3-kinase (PI3K); it is the second most frequently mutated gene following the TP53 gene. In the clinical setting, PIK3CA mutations may have favorable prognostic value for hormone receptor-positive breast cancer patients and, during the past few years, PIK3CA mutations of cell-free DNA (cfDNA) have attracted attention as a potential noninvasive biomarker of cancer. However, there are few reports on the clinical implications of PIK3CA mutations for TNBC patients. We investigated the PIK3CA major mutation status of cfDNA as a noninvasive biomarker of cancer using droplet digital polymerase chain reaction (ddPCR), which has high level sensitivity and specificity for cancer mutation, in early-stage 49 triple negative breast cancer (TNBC) patients. A total of 12 (24.4%) of 49 patients had PIK3CA mutations of cfDNA. In a median follow up of 54.4 months, the presence of PIK3CA mutations of cfDNA had significant impacts on relapse-free survival (RFS; P = 0.0072) and breast cancer-specific survival (BCSS; P = 0.016), according to the log-lank test. In a Cox proportional hazards model, the presence of PIK3CA mutations of cfDNA had significant prognostic value in the univariate and multivariate analysis. Additionally, the presence of PIK3CA mutations of cfDNA was significantly correlated with positive androgen receptor phosphorylated form depending on PI3K signaling pathway (pAR) which is independent favorable prognostic factors of TNBC. We demonstrated that the presence of PIK3CA major mutations of cfDNA could be a discriminatory predictor of RFS and BCSS in early-stage TNBC patients and it was associated with PI3K pathway-dependent AR phosphorylation. PMID- 26353838 TI - SHAPE directed RNA folding. AB - SUMMARY: Chemical mapping experiments allow for nucleotide resolution assessment of RNA structure. We demonstrate that different strategies of integrating probing data with thermodynamics-based RNA secondary structure prediction algorithms can be implemented by means of soft constraints. This amounts to incorporating suitable pseudo-energies into the standard energy model for RNA secondary structures. As a showcase application for this new feature of the ViennaRNA Package we compare three distinct, previously published strategies to utilize SHAPE reactivities for structure prediction. The new tool is benchmarked on a set of RNAs with known reference structure. AVAILABILITY AND IMPLEMENTATION: The capability for SHAPE directed RNA folding is part of the upcoming release of the ViennaRNA Package 2.2, for which a preliminary release is already freely available at http://www.tbi.univie.ac.at/RNA. CONTACT: michael.wolfinger@univie.ac.at SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26353839 TI - RNF: a general framework to evaluate NGS read mappers. AB - MOTIVATION: Read simulators combined with alignment evaluation tools provide the most straightforward way to evaluate and compare mappers. Simulation of reads is accompanied by information about their positions in the source genome. This information is then used to evaluate alignments produced by the mapper. Finally, reports containing statistics of successful read alignments are created.In default of standards for encoding read origins, every evaluation tool has to be made explicitly compatible with the simulator used to generate reads. RESULTS: To solve this obstacle, we have created a generic format Read Naming Format (Rnf) for assigning read names with encoded information about original positions. Futhermore, we have developed an associated software package RnfTools containing two principal components. MIShmash applies one of popular read simulating tools (among DwgSim, Art, Mason, CuReSim, etc.) and transforms the generated reads into Rnf format. LAVEnder evaluates then a given read mapper using simulated reads in Rnf format. A special attention is payed to mapping qualities that serve for parametrization of Roc curves, and to evaluation of the effect of read sample contamination. AVAILABILITY AND IMPLEMENTATION: RnfTools: http://karel brinda.github.io/rnftools Spec. of Rnf: http://karel-brinda.github.io/rnf-spec CONTACT: karel.brinda@univ-mlv.fr. PMID- 26353840 TI - Reveel: large-scale population genotyping using low-coverage sequencing data. AB - MOTIVATION: Population low-coverage whole-genome sequencing is rapidly emerging as a prominent approach for discovering genomic variation and genotyping a cohort. This approach combines substantially lower cost than full-coverage sequencing with whole-genome discovery of low-allele frequency variants, to an extent that is not possible with array genotyping or exome sequencing. However, a challenging computational problem arises of jointly discovering variants and genotyping the entire cohort. Variant discovery and genotyping are relatively straightforward tasks on a single individual that has been sequenced at high coverage, because the inference decomposes into the independent genotyping of each genomic position for which a sufficient number of confidently mapped reads are available. However, in low-coverage population sequencing, the joint inference requires leveraging the complex linkage disequilibrium (LD) patterns in the cohort to compensate for sparse and missing data in each individual. The potentially massive computation time for such inference, as well as the missing data that confound low-frequency allele discovery, need to be overcome for this approach to become practical. RESULTS: Here, we present Reveel, a novel method for single nucleotide variant calling and genotyping of large cohorts that have been sequenced at low coverage. Reveel introduces a novel technique for leveraging LD that deviates from previous Markov-based models, and which is aimed at computational efficiency as well as accuracy in capturing LD patterns present in rare haplotypes. We evaluate Reveel's performance through extensive simulations as well as real data from the 1000 Genomes Project, and show that it achieves higher accuracy in low-frequency allele discovery and substantially lower computation cost than previous state-of-the-art methods. AVAILABILITY AND IMPLEMENTATION: http://reveel.stanford.edu/ CONTACT: : serafim@cs.stanford.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26353841 TI - [Adolescent scoliosis : From deformity to treatment]. AB - Scoliosis affects up to 6 % of the population. The resulting spine deformity, the increasing risk of back pain, cosmetic aspects, pulmonary disorders if the Cobb angle is > 80 degrees , and the progress of the deformity to > 50 degrees after the end of growth indicate non-operative or operative therapy. In daily clinical practice, the classifications of scoliosis allow the therapy to be adapted. Classifications consider deformity, topography of the scoliosis, and the age at diagnosis. This publication gives an overview of the relevant and most common classifications in the treatment of adolescent scoliosis. For evaluation, the deformity measurement on the coronary radiographic projection of the total spine (Cobb angle) is relevant to therapy. The classification of topography, form, and the sagittal profile of the deformity of the spine are useful for preoperative planning of the fusion level. Classifications that take into account the age at the time of the diagnosis of scoliosis differentiate among early onset scoliosis (younger than 10 years of age), adolescent scoliosis (up to the end of growth), and adult scoliosis. Early onset scoliosis is subdivided by age and etiology. Therapy is derived from the classification of clinical and radiological findings. Classifications that take into account clinical and radiological parameters are essential components of modern scoliosis therapy. PMID- 26353842 TI - Inhibition of p38 MAPK activation attenuates esophageal mucosal damage in a chronic model of reflux esophagitis. AB - BACKGROUND: Reflux esophagitis (RE) is one of the common gastrointestinal diseases that are increasingly recognized as a significant health problem. This study was designed to investigate the role of p38 mitogen-activated protein kinase (MAPK) in experimental chronic RE model of rats. METHODS: Chronic acid RE rats were induced by fundus ligation and partial obstruction of the pylorus and treated with SB203580 (a p38 MAPK inhibitor, i.p., 1 mg/kg/day) for 14 days. KEY RESULTS: Immunohistochemical staining and Western blotting results revealed the activation of p38 MAPK signaling in the esophagus mucosa 14 days post injury. Through gross and histological assessment, we found that inhibition of p38 MAPK activation by SB203580 attenuated esophageal mucosal damage in RE rats. Inhibition of p38 MAPK activation in RE rats attenuated esophageal barrier dysfunction, through enhancing the expression of tight junction proteins and reducing the expression of matrix matalloproteinases-3 and -9. Inhibition of p38 MAPK activation in RE rats reduced CD68-positive cells in esophagus mucosa and mRNA levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL 1beta in esophagus and protein levels of TNF-alpha, IL-6, and IL-1beta in serum. In addition, we found that inhibition of p38 MAPK activation in RE rats suppressed protein expression of inducible nitric oxide synthase and reduced formation of nitric oxide (NO), 3-nitrotyrosin, and malondialdehyde in esophagus. CONCLUSIONS & INFERENCES: Inhibition of p38 MAPK activation attenuated esophageal mucosal damage in acid RE rats, possibly by modulating esophageal barrier function and regulating inflammatory cell recruitment, and the subsequent formation of cytokines, NO, and reactive oxygen species. PMID- 26353843 TI - Grazoprevir plus peginterferon and ribavirin in treatment-naive patients with hepatitis C virus genotype 1 infection: a randomized trial. AB - Grazoprevir (MK-5172, Merck & Co., Inc.) is a selective inhibitor of the hepatitis C virus (HCV) NS3/4a protease. The aim of this study was to evaluate the safety and efficacy of grazoprevir at doses of 25-100 mg/day in combination with peginterferon and ribavirin (PEG-IFN/RBV). In this randomized, dose-ranging, multicentre trial, treatment-naive adults with chronic HCV genotype 1 infection received once-daily grazoprevir 25 mg, 50 mg or 100 mg plus PEG-IFN/RBV for 12 weeks. Patients with quantifiable HCV RNA (>=25 IU/mL) at week 4 received an additional 12 weeks of PEG-IFN/RBV. The primary endpoint was sustained virologic response (HCV RNA <25 IU/mL 12 weeks after completing therapy [SVR12]). Eighty seven patients were randomly assigned and received >=1 dose of therapy. Median time to undetectable HCV RNA was 16 days in the 100-mg arm and 22 days in the 25- and 50-mg arms. All patients except one had HCV RNA undetectable or unquantifiable at week 4 and received 12 weeks of therapy. SVR12 was achieved by 13 of 24 (54.2%), 21 of 25 (84.0%) and 23 of 26 (88.5%) patients in the 25-, 50- and 100-mg arms, respectively (per-protocol analysis). Three patients discontinued as a result of nonserious adverse events (AEs) and three patients experienced serious AEs. Transaminase elevations occurred in two patients (one each in the 25- and 100-mg arms). CONCLUSION: These data support further study of the grazoprevir 100-mg dose. Phase 3 studies of grazoprevir 100 mg in combination with elbasvir are currently ongoing (NCT01710501; protocol P038). PMID- 26353845 TI - Female urinary incontinence health information quality on the Internet: a multilingual evaluation. AB - INTRODUCTION AND HYPOTHESIS: The quality of Internet information on female urinary incontinence is considered variable. No comprehensive analysis exists to support this. We compared the quality of current Internet information for common layperson terminology on female urinary incontinence across four Western languages and a comparative analysis of website sponsors. METHODS: World Health Organization Health on the Net (HON) principles may be applied to websites using an automated toolbar function. We used the Google search engine; 10,200 websites were identified using keywords related to female urinary incontinence and treatments in English, French, German and Spanish. The first 150 websites in each language had HON principles examined, whilst a further analysis of site sponsorship was undertaken. RESULTS: The total number of websites for each term is variable. "Female sling surgery" had the most websites with approximately 18 million, whereas "colposuspension" had the least with only 159,890 websites. Regardless of language, very few female urinary incontinence websites were HON accredited (p < 0.0001). Linguistically, French (18%) and English (16%) had the greatest percentage of HON-accredited sites. Tertiles (thirds) of the first 150 websites returned the higher percentage of HON-accredited websites (p < 0.0001). Websites were largely sponsored by physicians/surgeons. CONCLUSIONS: The lack of validation of most female urinary incontinence websites should be appreciated by clinicians. Additionally, discrepancies exist in the quality and number of websites across conditions, languages and also between medical and alternative terms. Clinicians should participate in and encourage the development of informative, ethical and reliable health websites on the Internet and direct patients to them. PMID- 26353847 TI - A review of the pelvic organ prolapse quantification system in China. AB - INTRODUCTION AND HYPOTHESIS: Unified staging systems for pelvic organ prolapse (POP) have been established. We examined the application of the POP quantification (POP-Q) system in China by examining its use in scientific journal articles. METHODS: Relevant articles were identified by searching the Sinomed database using the terms: uterus prolapse, cystocele, proctocele, prolapse, and pelvic floor; limited to Chinese core journals in obstetrics and gynecology, from January 2004 to December 2014. We analyzed systems for grading POP severity and the adoption of POP-Q in different article categories and hospitals of different levels. For the last decade, with two 5-year groups (2005-2009; 2010-2014), the chi(2) test was used to evaluate inter-group differences. RESULTS: In a total of 429 articles, 331 included a staging system, 70.7% of which used POP-Q. The POP-Q system first appeared in 2004 in China, was reported in 50% of articles in 2007, and its highest use occurred in 2012 (89.5%). In 234 POP-Q system-utilizing reports, operative treatment and basic research accounted for 73.1% and 14.0% respectively. POP-Q usage increased from 2005-2009 to 2010-2014 in surgery related articles (54.2% vs 85.2%; P = 0.000). The proportion of reports using POP Q in level I, II, and III hospitals was 20.0%, 35.4%, and 77.8% respectively. CONCLUSIONS: The POP-Q system, first used in 2004 in China, is now the most commonly used grading system, with surgery reports and level III hospitals accounting for the largest proportion of POP-Q applications. PMID- 26353846 TI - Mesenchymal stem cell therapy in a rat model of birth-trauma injury: functional improvements and biodistribution. AB - INTRODUCTION AND HYPOTHESIS: We evaluated the potential role of human mesenchymal stem cells (hMSCs) in improvement of urinary continence following birth-trauma injury. METHODS: Human MSCs were injected periurethrally or systemically into rats immediately after vaginal distention (VD) (n = 90). Control groups were non VD (uninjured/untreated, n = 15), local or systemic saline (injection/control, n = 90), and dermofibroblast (cell therapy/control, n = 90). Leak-point pressure (LPP) was measured 4, 10, and 14 days later. Urethras were morphometrically evaluated. In another sets of VD and non-VD rats, the fate of periurethrally injected hMSC, biodistribution, and in vivo viability was studied using human Alu genomic repeat staining, PKH26 labeling, and luciferase-expression labeling, respectively. RESULTS: Saline- and dermofibroblast-treated control rats demonstrated lower LPP than non-VD controls at days 4 and 14 (P < 0.01). LPP after systemic hMSC and periurethral hMSC treatment were comparable with non-VD controls at 4, 10, and 14 days (P > 0.05). Local saline controls demonstrated extensive urethral tissue bleeding. The connective tissue area/urethral section area proportion and vascular density were higher in the local hMSC- versus the saline-treated group at 4 and 14 days, respectively. No positive Alu-stained nuclei were observed in urethras at 4, 10, and 14 days. PKH26-labelled cells were found in all urethras at 2 and 24 h. Bioluminescence study showed increased luciferase expression from day 0 to 1 following hMSC injection. CONCLUSIONS: Human MSCs restored the continence mechanism with an immediate and sustained effect in the VD model, while saline and dermofibroblast therapy did not. Human MSCs remained at the site of periurethral injection for <7 days. We hypothesize that periurethral hMSC treatment improves vascular, connective tissue, and hemorrhage status of urethral tissues after acute VD injury. PMID- 26353844 TI - Cannabinoid Ligands and Alcohol Addiction: A Promising Therapeutic Tool or a Humbug? AB - The vast therapeutic potential of cannabinoids of both synthetic and plant derived origins currently makes these compounds the focus of a growing interest. Although cannabinoids are still illicit drugs, their possible clinical usefulness, including treatment of acute or neuropathic pain, have been suggested by several studies. In addition, some observations indicate that cannabinoid receptor antagonists may be useful for the treatment of alcohol dependence and addiction, which is a major health concern worldwide. While the synergism between alcohol and cannabinoid agonists (in various forms) creates undesirable side effects when the two are consumed together, the administration of CB1 antagonists leads to a significant reduction in alcohol consumption. Furthermore, cannabinoid antagonists also mitigate alcohol withdrawal symptoms. Herein, we present an overview of studies focusing on the effects of cannabinoid ligands (agonists and antagonists) during acute or chronic consumption of ethanol. PMID- 26353848 TI - Individual male perception of female genitalia. AB - INTRODUCTION AND HYPOTHESIS: Australian Medicare data show that the rates of cosmetic labiaplasty have tripled over the last decade; however, there is little understanding about the social factors that contribute to the popularity of female genital cosmetic surgeries (FGCS). The aim of this study was to investigate male perception of female genitalia and to assess men's awareness of FGCS and whether these surgeries are viewed as a positive and acceptable option. METHODS: A cross-sectional study of male adults in the Townsville region was conducted via an online questionnaire. RESULTS: A total of 500 online surveys were sent out and 248 respondents were included in the study; 49.2 % of participants do not have a preferred appearance of labia minora and 70.4 % of men are aware of FGCS, but 53.8 % do not believe that FGCS is a good option for women. Only 14 % of men supported genital cosmetic surgery, while 29.6 % are undecided about the practice. The most common preferred pubic hair appearance is completely hairless (45 %). CONCLUSIONS: This study indicates that the majority of men do not have a preferred appearance for female genitalia, nor do they support FGCS or consider discussing genital surgery with their partner. The major limitation of the study is that the participants' age distribution was skewed heavily towards the younger demographic, with 18- to 24-year-old men comprising 81.5 % of respondents. PMID- 26353849 TI - Towards an understanding of adult judgments of synergistic health benefits. AB - OBJECTIVE: Numerous scientific studies show that certain combinations of dietary and/or lifestyle factors produce health benefits which are greater than the sum of the benefits associated with each factor alone. To address an existing knowledge gap, we assessed the extent to which individuals understand that certain combinations present these 'synergistic health benefits'. DESIGN: Health benefit judgments were obtained from lay adults for a range of dietary and/or lifestyle combinations that have been found to present synergistic benefits. Association between these judgments and socio-cognitive characteristics such as numeracy, education, and health interest (HI) were examined. METHODS: Three hundred and fifty-two Swiss adults were presented with a description of one of eight synergistically beneficial combinations. Each participant provided a categorical benefit judgment (i.e., subadditive, additive, or synergistic) for the combination and explained the cognitive reasoning underlying their judgment. Participants completed measures of numeracy and HI. RESULTS: The proportion of combinations judged to present a synergistic benefit was modest for 'macro-level' combinations (e.g., diet and exercise), but low for 'micro-level' combinations (e.g., two phytochemicals). Cognitive reasoning data showed that a higher proportion of judgments for micro-level (cf. macro-level) combinations were based on greater subjective epistemic uncertainty. Higher interest in health was associated with a better understanding of synergistic benefits, but numeracy and education level were not. CONCLUSIONS: There is considerable scope to improve the extent to which lay adults understand that specific combination of diet and lifestyle behaviours can synergistically benefit their health. Our results enable us to make informed recommendations for public health interventions. STATEMENT OF CONTRIBUTION: What is already known on this subject? Combining certain dietary and/or lifestyle factors can result in synergistic health benefits. People could maintain/enhance their health by combining these synergistic combinations. No previous studies have assessed the extent to which people understand that certain factors produce synergistic health benefits. What does this study add? This is the first study to identify that lay awareness of synergistic health benefits could be substantially improved. Neither education level nor numeracy moderate judgments of synergistic benefits, but health interest does. Individuals better understand that broad lifestyle behaviours (cf. specific foods and phytochemicals) are synergistic. PMID- 26353850 TI - IMP3 Is Strongly Expressed in Malignant Phyllodes Tumors of the Breast: An Immunohistochemical Study. AB - BACKGROUND: Phyllodes tumors (PTs) of the breast are rare biphasic neoplasms and are classified as benign, borderline, or malignant. Many biological markers have been studied to discriminate between different grades of PTs. IMP3 is a member of the insulin-like growth factor II mRNA binding protein (IMP) family and is expressed in developing tissues during embryogenesis, whereas in adult tissues it is found only at low or undetectable levels. IMP3 is considered a marker of biological aggressiveness in many cancers, including breast and lung. The aim of this study was to evaluate the immunohistochemical expression of IMP3 in a series of PTs and to determine its association with histological grade and clinical outcome. MATERIALS AND METHODS: We reviewed retrospectively 62 cases of PTs including their recurrences and 20 cases of fibroadenoma. PTs have been classified as benign in 40 cases, borderline in 13 cases, and malignant in 9 cases. RESULTS: There were significant differences in IMP3 expression: in malignant PTs IMP3 expression was higher (56% of cases) than in borderline (15%) and benign cases (5%), (P = .001). Fibroadenoma showed no expression for IMP3. IMP3 expression was different in cases with recurrence than cases without recurrence. Furthermore, 3 of the recurrences had a higher histological grade with a positive IMP3 expression compared with the primary tumor. CONCLUSIONS: This is the first study evaluating the IMP3 immunohistochemical expression in PTs. Its expression correlates with histological grade and could be used in the differential diagnosis of fibroepithelial tumors and in predicting a more aggressive behavior. PMID- 26353851 TI - Classification of the Seborrheic Keratosis. PMID- 26353852 TI - Composite Epstein-Barr Virus-Associated B-Cell Lymphoproliferative Disorder and Tubular Adenoma in a Rectal Polyp. AB - Composite tumors are formed when there is intermingling between two components of separate tumors seen histologically. Cases demonstrating composite tubular adenoma with other types of tumors in the colon are rare. Composite tubular adenomas with nonlymphoid tumors including carcinoids, microcarcinoids, and small cell undifferentiated carcinoma have been reported in the literature. The occurrence of composite lymphoma and tubular adenoma within the colorectal tract is extremely rare. Only three cases have been reported and include one case of mantle cell lymphoma and two cases of diffuse large B-cell lymphoma arising in composite tubular adenomas. We present the first case of composite Epstein-Barr virus-associated B-cell lymphoproliferative disorder and tubular adenoma in a rectal polyp with a benign endoscopic appearance. PMID- 26353853 TI - Giant Cell Arteritis of the Female Genital Tract With Occult Temporal Arteritis and Marginal Zone Lymphoma Harboring Novel 20q Deletion: A Case Report and Literature Review. AB - Giant cell arteritis (GCA) is an immunologically mediated vasculitis of large and medium-sized vessels, typically affecting the cranial arteries and usually occurring in the elderly. GCA of the female genital tract is extremely rare with only 31 cases reported in the English literature. An 83-year-old white female with postmenopausal vaginal bleeding revealed an endometrial polyp on pelvic ultrasonography following which polypectomy and subsequently hysterectomy with bilateral salpingo-oophorectomy was done. Microscopy revealed a well differentiated endometrioid adenocarcinoma. Interestingly, classic GCA involving numerous small to medium-sized arteries of the cervix, myometrium, bilateral fallopian tubes, and ovaries was also identified. Hematologic evaluation revealed marginal zone lymphoma with an exceptionally rare 20q deletion. Bilateral temporal artery biopsy was done subsequently, which exhibited GCA on microscopy. Corticosteroid was started that improved her polymyalgia rheumatica symptoms. The patient is on follow-up for 3 years and is doing well. To our knowledge, this is the first case of GCA of the female genital tract associated with a lymphoma and the second case of marginal zone lymphoma with the novel 20q deletion. PMID- 26353854 TI - Ki67 Heterogeneity in Estrogen Receptor-Positive Breast Cancers: Which Tumor Type Has the Most Heterogeneity? AB - Heterogeneity of Ki67 expression, often seen in breast cancer, can make evaluation of the expression of this marker difficult and give rise to confusion when considering adjuvant treatments for patients. Herein, we investigated estrogen receptor-positive breast cancers to reveal the tumor characteristics associated with Ki67 heterogeneity. Surgical specimens from 85 invasive ductal carcinomas of no special type and 13 invasive lobular carcinomas were examined. We first calculated the differences between Ki67 expression in a hot spot and those in 4 random fields on the same slide. We then evaluated Ki67 heterogeneity within the tumor, based on these differences. Among clinicopathological factors, solid-tubular carcinoma, an architectural growth pattern subtype of invasive ductal carcinoma, correlated with high Ki67 heterogeneity (P < .05). Our results indicate that we might need to be aware of histological patterns when selecting appropriate microscopic fields for evaluating Ki67 expression. PMID- 26353855 TI - A Rare Polypoid Lesion of the Jejunum. PMID- 26353856 TI - The influence of power and reason on young Maya children's endorsement of testimony. AB - Two important parenting strategies are to impose one's power and to use reasoning. The effect of these strategies on children's evaluation of testimony has received very little attention. Using the epistemic vigilance framework, we predict that when the reasoning cue is strong enough it should overcome the power cue. We test this prediction in a population for which anthropological data suggest that power is the prominent strategy while reasoning is rarely relied on in the interactions with children. In Experiment 1, 4- to 6-year-old children from a traditional Maya population are shown to endorse the testimony supported by a strong argument over that supported by a weak argument. In Experiment 2, the same participants are shown to follow the testimony of a dominant over that of a subordinate. The participants are then shown to endorse the testimony of a subordinate who provides a strong argument over that of a dominant who provides either a weak argument (Experiment 3) or no argument (Experiment 4). Thus, when the power and reasoning cues conflict, reasoning completely trumps power. PMID- 26353857 TI - Targeting CD133(+) laryngeal carcinoma cells with chemotherapeutic drugs and siRNA against ABCG2 mediated by thermo/pH-sensitive mesoporous silica nanoparticles. AB - Mesoporous silica nanoparticles (MSNs) represent a new form of drug nanocarrier with thermo/pH-coupling sensitivity and site-specificity. CD133(+) Hep-2 laryngeal cancer cells are responsible for multidrug resistance due to elevated expression of ABCG2. Since positively charged nanoparticles could easily uptake nucleic acids, we examined the possibility of using this new drug delivery system to simultaneously deliver different chemotherapeutic drugs and siRNA targeting ABCG2. Our results demonstrated that both antitumor drugs and siRNA against ABCG2 were successfully delivered into CD133(+) cancer cells by loaded MSNs. Down regulation of ABCG2 significantly enhanced the efficacy of chemotherapeutic drug induced apoptosis in laryngeal carcinoma cells. Furthermore, the chemotherapeutic drug and siRNA loaded nanoparticles inhibited tumor growth in vivo in a laryngeal cancer mouse model. PMID- 26353858 TI - The clinical utility of image-guided iodine-125 seed in patients with unresectable pancreatic cancer. AB - In the present study, we investigated the clinical effects of image-guided iodine 125 ((125)I) seed on unresectable pancreatic cancer. Twenty-five patients with unresectable pancreatic cancer were enrolled in this study, including 13 patients with seed implantation and 12 patients as control. The survival status, clinical benefits, objective curative effects, and relevant tumor markers were analyzed to assess the feasibility and safety of interstitial (125)I seed implantation. We found that the clinical benefit rate of the seed implantation group is 92.3 % (12/13), compared with 41.7 % (5/12) in the control, and the difference was statistically significant (p < 0.01). Compared with control, patients with seed implantation had significantly shorter operative time, less bleeding, higher albumin, shorter periods to bowel movement, and normal diet as well as lower risk of complications (p < 0.001). The differences of objective curative effects adverse effects, complications, and median survival between these two groups were not significant statistically (p > 0.05). In conclusion, (125)I seed implantation provides a safe and effective method to inhibit the tumor development, relieve pain, and improve quality of life for unresectable pancreatic cancer. These findings need to be validated by conducting further studies with larger cohorts. PMID- 26353859 TI - Development of infants' segmentation of words from native speech: a meta-analytic approach. AB - Infants start learning words, the building blocks of language, at least by 6 months. To do so, they must be able to extract the phonological form of words from running speech. A rich literature has investigated this process, termed word segmentation. We addressed the fundamental question of how infants of different ages segment words from their native language using a meta-analytic approach. Based on previous popular theoretical and experimental work, we expected infants to display familiarity preferences early on, with a switch to novelty preferences as infants become more proficient at processing and segmenting native speech. We also considered the possibility that this switch may occur at different points in time as a function of infants' native language and took into account the impact of various task- and stimulus-related factors that might affect difficulty. The combined results from 168 experiments reporting on data gathered from 3774 infants revealed a persistent familiarity preference across all ages. There was no significant effect of additional factors, including native language and experiment design. Further analyses revealed no sign of selective data collection or reporting. We conclude that models of infant information processing that are frequently cited in this domain may not, in fact, apply in the case of segmenting words from native speech. PMID- 26353860 TI - Change detection on a hunch: pre-attentive vision allows "sensing" of unique feature changes. AB - Studies on change detection and change blindness have investigated the nature of visual representations by testing the conditions under which observers are able to detect when an object in a complex scene changes from one moment to the next. Several authors have proposed that change detection can occur without identification of the changing object, but the perceptual processes underlying this phenomenon are currently unknown. We hypothesized that change detection without localization or identification occurs when the change happens outside the focus of attention. Such changes would usually go entirely unnoticed, unless the change brings about a modification of one of the feature maps representing the scene. Thus, the appearance or disappearance of a unique feature might be registered even in the absence of focused attention and without feature binding, allowing for change detection, but not localization or identification. We tested this hypothesis in three experiments, in which changes either involved colors that were already present elsewhere in the display or entirely unique colors. Observers detected whether any change had occurred and then localized or identified the change. Change detection without localization occurred almost exclusively when changes involved a unique color. Moreover, change detection without localization for unique feature changes was independent of the number of objects in the display and independent of change identification. These findings suggest that pre-attentive registration of a change on a feature map can give rise to a conscious experience even when feature binding has failed: that something has changed without knowing what or where. PMID- 26353861 TI - Atg9 is required for intraluminal vesicles in amphisomes and autolysosomes. AB - Autophagy is an intracellular recycling and degradation process, which is important for energy metabolism, lipid metabolism, physiological stress response and organism development. During Drosophila development, autophagy is up regulated in fat body and midgut cells, to control metabolic function and to enable tissue remodelling. Atg9 is the only transmembrane protein involved in the core autophagy machinery and is thought to have a role in autophagosome formation. During Drosophila development, Atg9 co-located with Atg8 autophagosomes, Rab11 endosomes and Lamp1 endosomes-lysosomes. RNAi silencing of Atg9 reduced both the number and the size of autophagosomes during development and caused morphological changes to amphisomes/autolysosomes. In control cells there was compartmentalised acidification corresponding to intraluminal Rab11/Lamp-1 vesicles, but in Atg9 depleted cells there were no intraluminal vesicles and the acidification was not compartmentalised. We concluded that Atg9 is required to form intraluminal vesicles and for localised acidification within amphisomes/autolysosomes, and consequently when depleted, reduced the capacity to degrade and remodel gut tissue during development. PMID- 26353862 TI - Influence of age, irradiation and humanization on NSG mouse phenotypes. AB - Humanized mice are frequently utilized in bench to bedside therapeutic tests to combat human infectious, cancerous and degenerative diseases. For the fields of hematology-oncology, regenerative medicine, and infectious diseases, the immune deficient mice have been used commonly in basic research efforts. Obstacles in true translational efforts abound, as the relationship between mouse and human cells in disease pathogenesis and therapeutic studies requires lengthy investigations. The interplay between human immunity and mouse biology proves ever more complicated when aging, irradiation, and human immune reconstitution are considered. All can affect a range of biochemical and behavioral functions. To such ends, we show age- and irradiation-dependent influences for the development of macrocytic hyper chromic anemia, myelodysplasia, blood protein reductions and body composition changes. Humanization contributes to hematologic abnormalities. Home cage behavior revealed day and dark cycle locomotion also influenced by human cell reconstitutions. Significant age-related day-to-day variability in movement, feeding and drinking behaviors were observed. We posit that this data serves to enable researchers to better design translational studies in this rapidly emerging field of mouse humanization. PMID- 26353863 TI - Canine MPV17 truncation without clinical manifestations. AB - Mitochondrial DNA depletion syndromes (MDS) are often serious autosomal recessively inherited disorders characterized by tissue-specific mtDNA copy number reduction. Many genes, including MPV17, are associated with the hepatocerebral form of MDS. MPV17 encodes for a mitochondrial inner membrane protein with a poorly characterized function. Several MPV17 mutations have been reported in association with a heterogeneous group of early-onset manifestations, including liver disease and neurological problems. Mpv17-deficient mice present renal and hearing defects. We describe here a MPV17 truncation mutation in dogs. We found a 1-bp insertion in exon 4 of the MPV17 gene, resulting in a frameshift and early truncation of the encoded protein. The mutation halves MPV17 expression in the lymphocytes of the homozygous dogs and the truncated protein is not translated in transfected cells. The insertion mutation is recurrent and exists in many unrelated breeds, although is highly enriched in the Boxer breed. Unexpectedly, despite the truncation of MPV17, we could not find any common phenotypes in the genetically affected dogs. The lack of observable phenotype could be due to a late onset, mild symptoms or potential tissue-specific compensatory mechanisms. This study suggests species-specific differences in the manifestation of the MPV17 defects and establishes a novel large animal model to further study MPV17 function and role in mitochondrial biology. PMID- 26353864 TI - Technical efficiency and productivity of Chinese county hospitals: an exploratory study in Henan province, China. AB - OBJECTIVES: Chinese county hospitals have been excessively enlarging their scale during the healthcare reform since 2009. The purpose of this paper is to examine the technical efficiency and productivity of county hospitals during the reform process, and to determine whether, and how, efficiency is affected by various factors. SETTING AND PARTICIPANTS: 114 sample county hospitals were selected from Henan province, China, from 2010 to 2012. OUTCOME MEASURES: Data envelopment analysis was employed to estimate the technical and scale efficiency of sample hospitals. The Malmquist index was used to calculate productivity changes over time. Tobit regression was used to regress against 4 environmental factors and 5 institutional factors that affected the technical efficiency. RESULTS: (1) 112 (98.2%), 112 (98.2%) and 104 (91.2%) of the 114 sample hospitals ran inefficiently in 2010, 2011 and 2012, with average technical efficiency of 0.697, 0.748 and 0.790, respectively. (2) On average, during 2010-2012, productivity of sample county hospitals increased by 7.8%, which was produced by the progress in technical efficiency changes and technological changes of 0.9% and 6.8%, respectively. (3) Tobit regression analysis indicated that government subsidy, hospital size with above 618 beds and average length of stay assumed a negative sign with technical efficiency; bed occupancy rate, ratio of beds to nurses and ratio of nurses to physicians assumed a positive sign with technical efficiency. CONCLUSIONS: There was considerable space for technical efficiency improvement in Henan county hospitals. During 2010-2012, sample hospitals experienced productivity progress; however, the adverse change in pure technical efficiency should be emphasised. Moreover, according to the Tobit results, policy interventions that strictly supervise hospital bed scale, shorten the average length of stay and coordinate the proportion among physicians, nurses and beds, would benefit hospital efficiency. PMID- 26353865 TI - Clinical and economic characteristics of emergency department visits due to acetaminophen toxicity in the USA. AB - OBJECTIVES: To estimate the number of acetaminophen (APAP) toxicity-related emergency department (ED) visits, and to assess their associated clinical and economic burden in the USA from 2006 to 2010. DESIGN: Cross-sectional, retrospective, large-scale database study. SETTING: Non-federal, non rehabilitation, community EDs in the USA. PARTICIPANTS: Inclusion criteria included any listed diagnosis identifying poisoning by aromatic analgesics paracetamol/APAP or associated supplementary code. Generalised linear models were used to investigate the association between outcomes of inpatient admission, mortality, requirement of invasive mechanical ventilation, charges and inpatient lengths of stay based on patient, hospital and clinical characteristics. RESULTS: Across the 625.2 million ED visits in the USA from 2006 to 2010, 411,811 APAP related toxicity ED visits were observed, with 45.5% resulting in inpatient admission, 4.7% requiring invasive mechanical ventilation and 0.6% involving death. Overall, the incidence proportion was 27.10 per 100,000 US population, exceeding 70 per 100,000 at age 2 years and ages 16-18 years. The total national bill was $1.06 billion per year (US$ 2014), and predominantly involved females (65.5%) and intentional self-harm (58.4%), which were notably higher within the 12-20 years age category (female(12-20 years)=74.8%, intentional self-harm(12-20 years)=71.4%). Behavioural and mental health comorbidities were relatively common and associated with an increased relative risk of admission and likelihood of charges almost entirely across all age categories of >=12 years within the multivariable analyses. The number of ED visits did not appreciably change over time, decreasing by <2% from 2006 to 2010 (n=1351). Multivariable results also suggested no consistent change in outcomes across the study's time horizon. CONCLUSIONS: A substantial public health impact of APAP toxicity-related cases was observed in the US from 2006 to 2010, with incidence proportions peaking at age 2 years and ages 16-18 years. After controlling for numerous factors, no consistent change was observed over the 5-year time horizon concerning outcomes of admission, mortality, invasive mechanical ventilation, charges or length of stay. PMID- 26353866 TI - Clinical deterioration in older adults with delirium during early hospitalisation: a prospective cohort study. AB - OBJECTIVES: To measure the prevalence and incidence of delirium in older adults as they transition from the emergency department (ED) to the inpatient ward, and to determine the association between delirium during early hospitalisation and subsequent clinical deterioration. DESIGN: Prospective cohort study. SETTING: Urban tertiary care hospital in Bronx, New York. PARTICIPANTS: Adults aged 65 years or older admitted to the inpatient ward from the ED (n=260). MEASUREMENTS: Beginning in the ED, delirium was assessed daily for 3 days, using the Confusion Assessment Method for the Intensive Care Unit. OUTCOMES: (1) Clinical deterioration, defined as unanticipated intensive care unit (ICU) admission or in hospital death (primary outcome); (2) decline in discharge status, defined as discharge to higher level of care, hospice or in-hospital death. RESULTS: 38 of 260 participants (15%) were delirious at least once during the first 3 days of hospitalisation. Of the 29 (11%) patients with delirium in the ED (ie, hospital day 1), delirium persisted into hospital day 2 in 72% (n=21), and persisted for all 3 days in 52% (n=15). In multivariate analyses, as little as 1 episode of delirium during the first 3 days was associated with increased odds of unanticipated ICU admission or in-hospital death (adjusted OR 8.07 (95% CI 1.91 to 34.14); p=0.005). Delirium that persisted for all 3 days was associated with a decline in discharge status, even after adjusting for factors such as severity of illness and baseline cognitive impairment (adjusted OR 4.70 (95% CI 1.41 to 15.63); p=0.012). CONCLUSIONS: Delirium during the first few days of hospitalisation was associated with poor outcomes in older adults admitted from the ED to the inpatient ward. These findings suggest the need for serial delirium monitoring that begins in the ED to identify a high-risk population that may benefit from closer follow-up and intervention. PMID- 26353867 TI - Prevalence and sociodemographic risk factors of chlamydia, gonorrhoea and syphilis: a national multicentre STI survey in New Caledonia, 2012. AB - OBJECTIVES: To estimate prevalence and identify sociodemographic risk factors for Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT) and Treponema pallidum infections in New Caledonia. METHOD: A national cross-sectional survey was undertaken using a three-stage random sampling of general practice surgeries and public dispensaries. Participants were included through opportunistic screening and using a systematic step for selection. The study sample was weighted to the general population aged 18-49 years. Prevalence and risk factors were calculated by logistic regression. RESULTS: CT was the most common sexually transmitted infection, with a prevalence of 9% (95% CI 6.6% to %11.4), followed by NG 3.5% (95% CI 1.9% to 5.1%), previous or latent syphilis 3% (95% CI 1.7% to 4.3%), NG and CT co-infection 2.1% (95% CI 0.8% to 3.3%) and active syphilis 0.4% (95% CI 0.0% to 0.9%). Being from a young age group (18-25 years), being single, having a low level of education and province of residence were all associated with higher prevalence of all three STIs. Being of Melanesian origin was associated with higher prevalence of both CT and NG. There was a significant interaction between ethnic group and province of residence for prevalence of CT. Female gender was associated with higher prevalence of CT. CONCLUSIONS: The prevalence of CT was similar to estimates from other healthcare-based surveys from the Pacific, but higher for NG and lower for active syphilis infection. All sexually transmitted infections estimates were much higher than those found in population-based surveys from Europe and the USA. The sociodemographic risk factors identified in this study will help guide targeted prevention and control strategies in New Caledonia. PMID- 26353868 TI - Comparative efficacy and tolerability of first-generation and newer-generation antidepressant medications for depressive disorders in children and adolescents: study protocol for a systematic review and network meta-analysis. AB - INTRODUCTION: Depressive disorders are among the most common psychiatric disorders in children and adolescents, and have adverse effects on their psychosocial functioning. Questions concerning the efficacy and safety of antidepressant medications in the treatment of depression in children and adolescents, led us to integrate the direct and indirect evidence using network meta-analysis to create hierarchies of these drugs. METHODS AND ANALYSIS: Seven databases with PubMed, EMBASE, the Cochrane Library, Web of Science, CINAHL, LiLACS and PsycINFO will be searched from 1966 to December 2013 (updated to May, 2015). There are no restrictions on language or type of publication. Randomised clinical trials assessing first-generation and newer-generation antidepressant medications against active comparator or placebo as acute treatment for depressive disorders in children and adolescents (under 18 years of age) will be included. The primary outcome for efficacy will be mean improvement in depressive symptoms, as measured by the mean change score of a depression rating scale from baseline to post-treatment. The tolerability of treatment will be defined as side effect discontinuation, as defined by the proportion of patients who discontinued treatment due to adverse events during the trial. We will also assess the secondary outcome for efficacy (response rate), acceptability (all-cause discontinuation) and suicide-related outcomes. We will perform the Bayesian network meta-analyses for all relative outcome measures. Subgroup analyses and sensitivity analyses will be conducted to assess the robustness of the findings. DISSEMINATION: The network meta-analysis will provide useful information on antidepressant treatment for child and adolescent depression. The results will be disseminated through peer-reviewed publication or conference presentations. TRIAL REGISTRATION NUMBER: PROSPERO CRD42015016023. PMID- 26353869 TI - Carpal tunnel syndrome and computer exposure at work in two large complementary cohorts. AB - OBJECTIVES: The boom in computer use and concurrent high rates in musculoskeletal complaints and carpal tunnel syndrome (CTS) among users have led to a controversy about a possible link. Most studies have used cross-sectional designs and shown no association. The present study used longitudinal data from two large complementary cohorts to evaluate a possible relationship between CTS and the performance of computer work. SETTINGS AND PARTICIPANTS: The Cosali cohort is a representative sample of a French working population that evaluated CTS using standardised clinical examinations and assessed self-reported computer use. The PrediCTS cohort study enrolled newly hired clerical, service and construction workers in several industries in the USA, evaluated CTS using symptoms and nerve conduction studies (NCS), and estimated exposures to computer work using a job exposure matrix. PRIMARY AND SECONDARY OUTCOME MEASURES: During a follow-up of 3 5 years, the association between new cases of CTS and computer work was calculated using logistic regression models adjusting for sex, age, obesity and relevant associated disorders. RESULTS: In the Cosali study, 1551 workers (41.8%) completed follow-up physical examinations; 36 (2.3%) participants were diagnosed with CTS. In the PrediCTS study, 711 workers (64.2%) completed follow-up evaluations, whereas 31 (4.3%) had new cases of CTS. The adjusted OR for the group with the highest exposure to computer use was 0.39 (0.17; 0.89) in the Cosali cohort and 0.16 (0.05; 0.59) in the PrediCTS cohort. CONCLUSIONS: Data from two large cohorts in two different countries showed no association between computer work and new cases of CTS among workers in diverse jobs with varying job exposures. CTS is far more common among workers in non-computer related jobs; prevention efforts and work-related compensation programmes should focus on workers performing forceful hand exertion. PMID- 26353870 TI - Reasons for non-participation in the Northern Ireland Bowel Cancer Screening Programme: a qualitative study. AB - OBJECTIVES: To identify the reasons why some people do not participate in bowel cancer screening so that steps can be taken to improve informed decision-making. DESIGN: Qualitative study, using focus groups with thematic analysis of data to identify, analyse and report patterns. Transcripts were repeatedly read and inductively coded using a phenomenological perspective, and organised into key themes. SETTING: Belfast and Armagh, two areas of Northern Ireland with relatively low uptake of bowel cancer screening. PARTICIPANTS: Ten women and 18 men in three single-gender focus groups (two male and one female), each with 9-10 participants. Study participants were recruited by convenience sampling from the general public and were eligible for, but had not taken part in, the Northern Ireland Bowel Cancer Screening Programme. RESULTS: Key themes identified were fear of cancer; the test procedure; social norms; past experience of cancer and screening; lack of knowledge or understanding about bowel cancer screening; and resulting behaviour towards the test. Fear about receiving bad news and reluctance to conduct the test themselves were reactions that participants seemed willing to overcome after taking part in open discussion about the test. CONCLUSIONS: We identified barriers to participation in bowel cancer screening and used these insights to develop new materials to support delivery of the programme. Some of the issues raised have been identified in other UK settings, suggesting that knowledge about barriers, and strategies to improve uptake, may be generalisable. PMID- 26353871 TI - Impact of multiple liver resections prior to salvage liver transplantation on survival in patients with recurrent HCC. AB - OBJECTIVES: Salvage liver transplantation (SLT) is a controversial technique that has been reported to be acceptable for the management of patients with recurrent hepatocellular carcinoma (HCC) after primary hepatic resection (HR). However, whether the number of times liver resection is performed has an impact on survival after SLT has not yet been reported. DESIGN: Retrospective study. SETTING: The level of care is primary and the study was carried out at only 1 centre. PARTICIPANTS: The study included 59 patients who underwent SLT for HCC from September 2001 to December 2012. 51 patients underwent HR only once before SLT, while the remaining 8 patients underwent HR more than once before SLT (HR=2 [7], HR=3, [1]). PRIMARY AND SECONDARY OUTCOME MEASURES: In this study, the 1 year, 3-year and 5-year overall and tumour-free survival outcomes between the 2 groups were compared. RESULTS: There were no significant differences between patients who underwent HR once and those who underwent HR more than once with respect to overall or tumour-free survival after receiving SLT. The 1-year, 3 year and 5-year overall survival rates for patients who underwent HR once were 72.9%, 35.3% and 35.5% vs 50%, 50% and 50%, respectively (p=0.986), while the 1 year, 3-year and 5-year tumour-free survival rates for those who underwent HR more than once were 66.3%, 55.3% and 44.4% vs 40%, 40% and 40%, respectively (p=0.790). CONCLUSIONS: There was no significant difference in the survival rate of patients who underwent HR once before SLT and those who underwent HR more than once. This suggests that SLT is a reasonable choice for patients who suffer from recurrent HCC after HR. TRIAL REGISTRATION NUMBER: This is a retrospective study and no registry or number is required. PMID- 26353872 TI - Development and validation of risk prediction equations to estimate future risk of heart failure in patients with diabetes: a prospective cohort study. AB - OBJECTIVE: To develop and externally validate risk prediction equations to estimate the 10-year risk of heart failure in patients with diabetes, aged 25-84 years. DESIGN: Cohort study using routinely collected data from general practices in England between 1998 and 2014 contributing to the QResearch and Clinical Research Practice Datalink (CPRD) databases. SETTING: We used 763 QResearch practices to develop the equations. We validated it in 254 different QResearch practices and 357 CPRD practices. PARTICIPANTS: 437,806 patients in the derivation cohort; 137,028 in the QResearch validation cohort, and 197,905 in the CPRD validation cohort. MEASUREMENT: Incident diagnosis of heart failure recorded on the patients' linked electronic General Practitioner (GP), mortality, or hospital record. Risk factors included age, body mass index (BMI), systolic blood pressure, cholesterol/ high-density lipoprotein (HDL) ratio, glycosylated haemoglobin (HbA1c), material deprivation, ethnicity, smoking, diabetes duration, type of diabetes, atrial fibrillation, cardiovascular disease, chronic renal disease, and family history of premature coronary heart disease. METHODS: We used Cox proportional hazards models to derive separate risk equations in men and women for evaluation at 10 years. Measures of calibration, discrimination, and sensitivity were determined in 2 external validation cohorts. RESULTS: We identified 25,480 cases of heart failure in the derivation cohort, 8189 in the QResearch validation cohort, and 11,311 in the CPRD cohort. The equations included: age, BMI, systolic blood pressure, cholesterol/HDL ratio, HbA1c, material deprivation, ethnicity, smoking, duration and type of diabetes, atrial fibrillation, cardiovascular disease, and chronic renal disease. The equations had good performance in CPRD for women (R(2) of 41.2%; D statistic 1.71; and receiver operating characteristic curve (ROC) statistic 0.78) and men (38.7%, 1.63; and 0.77 respectively). CONCLUSIONS: We have developed and externally validated risk prediction equations to quantify absolute risk of heart failure in men and women with diabetes. These can be used to identify patients at high risk of heart failure for prevention or assessment of the disease. PMID- 26353873 TI - A protocol for developing early warning score models from vital signs data in hospitals using ensembles of decision trees. AB - INTRODUCTION: Multiple early warning scores (EWS) have been developed and implemented to reduce cardiac arrests on hospital wards. Case-control observational studies that generate an area under the receiver operator curve (AUROC) are the usual validation method, but investigators have also generated EWS with algorithms with no prior clinical knowledge. We present a protocol for the validation and comparison of our local Hamilton Early Warning Score (HEWS) with that generated using decision tree (DT) methods. METHODS AND ANALYSIS: A database of electronically recorded vital signs from 4 medical and 4 surgical wards will be used to generate DT EWS (DT-HEWS). A third EWS will be generated using ensemble-based methods. Missing data will be multiple imputed. For a relative risk reduction of 50% in our composite outcome (cardiac or respiratory arrest, unanticipated intensive care unit (ICU) admission or hospital death) with a power of 80%, we calculated a sample size of 17,151 patient days based on our cardiac arrest rates in 2012. The performance of the National EWS, DT-HEWS and the ensemble EWS will be compared using AUROC. ETHICS AND DISSEMINATION: Ethics approval was received from the Hamilton Integrated Research Ethics Board (#13-724 C). The vital signs and associated outcomes are stored in a database on our secure hospital server. Preliminary dissemination of this protocol was presented in abstract form at an international critical care meeting. Final results of this analysis will be used to improve on the existing HEWS and will be shared through publication and presentation at critical care meetings. PMID- 26353874 TI - Variation in use of non-surgical treatments among osteoarthritis patients in orthopaedic practice in the Netherlands. AB - OBJECTIVES: National and international evidence-based guidelines for hip and knee osteoarthritis (OA) recommend to start with non-surgical treatments, followed by surgical intervention if a patient does not respond sufficiently to non-surgical treatments, but there are indications that these are not optimally used. The aim of this study was to assess the extent to which all recommended non-surgical treatments were used by patients with hip or knee OA who receive(d) a total hip or knee replacement, as reported by patients and orthopaedic surgeons. SETTING: We performed two cross-sectional internet-based surveys among patients and orthopaedic surgeons throughout the Netherlands. PARTICIPANTS: 195 OA patients either have undergone total knee arthroplasty or total hip arthroplasty no longer than 12 months ago or being on the waiting list for surgery with a confirmed date within 3 months and 482 orthopaedic surgeons were invited to participate. PRIMARY AND SECONDARY OUTCOME MEASURES: The use of recommended non-surgical treatments including education about OA/treatment options, lifestyle advice, dietary therapy, physical therapy, acetaminophen, NSAIDs and glucocorticoid injections. RESULTS: 174 OA patients (93%) and 172 orthopaedic surgeons (36%) completed the surveys. Most recommended non-surgical treatments were given to the majority of patients (eg, 80% education about OA, 73% physical therapy, 72% acetaminophen, 80% NSAIDs). However, only 6% of patients and 10% of orthopaedic surgeons reported using a combination of all recommended treatments. Dietary therapy was used least frequently. Only 11% of overweight and 30% of obese participants reported having received dietary therapy and 28% of orthopaedic surgeons reported to prescribe dietary therapy to overweight patients. CONCLUSIONS: While most recommended non-surgical treatments were used frequently as single therapy, the combination is used in only a small percentage of OA patients. Especially, use of dietary therapy may be improved to help patients manage their symptoms, and potentially delay the need for joint arthroplasty. PMID- 26353875 TI - Treating Parents to Reduce NICU Transmission of Staphylococcus aureus (TREAT PARENTS) trial: protocol of a multisite randomised, double-blind, placebo controlled trial. AB - INTRODUCTION: More than 33,000 healthcare-associated infections occur in neonatal intensive care units (NICUs) each year in the USA. Parents, rather than healthcare workers, may be a reservoir from which neonates acquire Staphylococcus aureus (S. aureus) colonisation in the NICU. This study looks to measure the effect of treating parents with short course intranasal mupirocin and topical chlorhexidine antisepsis on acquisition of S. aureus colonisation and infection in neonates. METHODS AND ANALYSIS: The TREAT PARENTS trial (Treating Parents to Reduce Neonatal Transmission of S. aureus) is a multicentre randomised, masked, placebo-controlled trial. Shortly after a neonate is admitted to the NICU, parents will be tested for S. aureus colonisation. If either parent screens positive for S. aureus, then both parents as a pair will be enrolled and randomised to one of the two possible masked treatment arms. Arm 1 will include assignment to intranasal 2% mupirocin plus topical antisepsis with chlorhexidine gluconate impregnated cloths for 5 days. Arm 2 will include assignment to placebo ointment and placebo cloths for skin antisepsis for 5 days. The primary outcome will be neonatal acquisition of an S. aureus strain that is concordant to the parental baseline S. aureus strain as determined by periodic surveillance cultures or a culture collected during routine clinical care that grows S. aureus. Secondary outcomes will include neonatal acquisition of S. aureus, neonatal S. aureus infection, eradication of S. aureus colonisation in parents, natural history of S. aureus colonisation in parents receiving placebo, adverse reactions to treatment, feasibility of intervention, and attitudes and behaviour in consented parents. Four hundred neonate-parent pairs will be enrolled. ETHICS AND DISSEMINATION: The study was approved by Johns Hopkins University IRB in June 2014 (IRB number 00092982). Protocol V.7 was approved in November 2014. Findings will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT02223520. PMID- 26353876 TI - Eliciting preferences for waterpipe tobacco smoking using a discrete choice experiment: implications for product regulation. AB - OBJECTIVES: Waterpipe smoking is highly prevalent among university students, and has been increasing in popularity despite mounting evidence showing it is harmful to health. The aim of this study was to measure preferences for waterpipe smoking and determine which product characteristics are most important to smokers. SETTING: A large university in the Southeastern USA. PARTICIPANTS: Adult waterpipe smokers attending the university (N=367). DESIGN: Participants completed an Internet-based discrete choice experiment to reveal their preferences for, and trade-offs between, the attributes of hypothetical waterpipe smoking sessions. Participants were presented with waterpipe lounge menus, each with three fruit-flavoured options and one tobacco flavoured option, in addition to an opt out option. Nicotine content and price were provided for each choice. Participants were randomised to either receive menus with a text-only health warning message or no message. OUTCOME MEASURES: Multinomial and nested logit models were used to estimate the impact on consumer choice of attributes and between-subject assignment of health warnings respectively. RESULTS: On average, participants preferred fruit-flavoured varieties to tobacco flavour. They were averse to options labelled with higher nicotine content. Females and non-smokers of cigarettes were more likely than their counterparts to prefer flavoured and nicotine-free varieties. Participants exposed to a health warning were more likely to opt out. CONCLUSIONS: Fruit-flavoured tobacco and lower nicotine content labels, two strategies widely used by the industry, increase the demand for waterpipe smoking among young adults. Waterpipe-specific regulation should limit the availability of flavoured waterpipe tobacco and require accurate labelling of constituents. Waterpipe-specific tobacco control regulation, along with research to inform policy, is required to curb this emerging public health threat. PMID- 26353878 TI - Structural and Perfusion Abnormalities of Brain on MRI and Technetium-99m-ECD SPECT in Children With Cerebral Palsy: A Comparative Study. AB - Cerebral palsy has traditionally been associated with hypoxic ischemic brain damage. This study was undertaken to demonstrate structural and perfusion brain abnormalities. Fifty-six children diagnosed clinically as having cerebral palsy were studied between 1 to 14 years of age and were subjected to 3 Tesla magnetic resonance imaging (MRI). Brain and Technetium-99m-ECD brain single-photon emission computed tomography (SPECT) scan. Male to female ratio was 1.8:1 with a mean age of 4.16 +/- 2.274 years. Spastic cerebral palsy was the most common type, observed in 91%. Birth asphyxia was the most common etiology (69.6%). White matter changes (73.2%) such as periventricular leukomalacia and corpus callosal thinning were the most common findings on MRI. On SPECT all cases except one revealed perfusion impairments in different regions of brain. MRI is more sensitive in detecting white matter changes, whereas SPECT is better in detecting cortical and subcortical gray matter abnormalities of perfusion. PMID- 26353877 TI - Working memory training in children: Effectiveness depends on temperament. AB - Studies revealing transfer effects of working memory (WM) training on non-trained cognitive performance of children hold promising implications for scholastic learning. However, the results of existing training studies are not consistent and provoke debates about the potential and limitations of cognitive enhancement. To examine the influence of individual differences on training outcomes is a promising approach for finding causes for such inconsistencies. In this study, we implemented WM training in an elementary school setting. The aim was to investigate near and far transfer effects on cognitive abilities and academic achievement and to examine the moderating effects of a dispositional and a regulative temperament factor, neuroticism and effortful control. Ninety-nine second-graders were randomly assigned to 20 sessions of computer-based adaptive WM training, computer-based reading training, or a no-contact control group. For the WM training group, our analyses reveal near transfer on a visual WM task, far transfer on a vocabulary task as a proxy for crystallized intelligence, and increased academic achievement in reading and math by trend. Considering individual differences in temperament, we found that effortful control predicts larger training mean and gain scores and that there is a moderation effect of both temperament factors on post-training improvement: WM training condition predicted higher post-training gains compared to both control conditions only in children with high effortful control or low neuroticism. Our results suggest that a short but intensive WM training program can enhance cognitive abilities in children, but that sufficient self-regulative abilities and emotional stability are necessary for WM training to be effective. PMID- 26353879 TI - Validity of the Child Facial Coding System for the Assessment of Acute Pain in Children With Cerebral Palsy. AB - The purpose of the current study was to examine the concurrent and discriminant validity of the Child Facial Coding System for children with cerebral palsy. Eighty-five children (mean = 8.35 years, SD = 4.72 years) were videotaped during a passive joint stretch with their physiotherapist and during 3 time segments: baseline, passive joint stretch, and recovery. Children's pain responses were rated from videotape using the Numerical Rating Scale and Child Facial Coding System. Results indicated that Child Facial Coding System scores during the passive joint stretch significantly correlated with Numerical Rating Scale scores (r = .72, P < .01). Child Facial Coding System scores were also significantly higher during the passive joint stretch than the baseline and recovery segments (P < .001). Facial activity was not significantly correlated with the developmental measures. These findings suggest that the Child Facial Coding System is a valid method of identifying pain in children with cerebral palsy. PMID- 26353880 TI - Experimental Therapeutic Trial Design for Pediatric Brain Tumors. AB - Pediatric brain tumors are the leading cause of cancer-related death during childhood. Since the first pediatric brain tumor clinical trials, the field has seen improved outcomes in some, but not all tumor types. In the past few decades, a number of promising new therapeutic agents have emerged, yet only a few of these agents have been incorporated into clinical trials for pediatric brain tumors. In this review, the authors discuss the process of and challenges in pediatric clinical trial design; this will allow for highly efficient and effective clinical trials with appropriate endpoints to ensure rapid and safe investigation of novel therapeutics for children with brain tumors. PMID- 26353881 TI - Disability Discrimination and Obesity: The Big Questions? AB - Obesity discrimination in employment and recruitment has become a topic of focus for research examination with increasing reports of discrimination by colleagues and managers. Whilst a limited number of legal cases have emerged, disability law is consulted in line with the expectation of anti-discriminatory practices at work. In line with disability law, whether obesity is defined as a disability or not has an impact on the outcome of a court ruling. Ambiguity when defining obesity through either the medical or social model means there are many questions that remain unanswered which might lead to inconsistency in court rulings. PMID- 26353882 TI - Causes of Vitamin D Deficiency and Effect of Vitamin D Supplementation on Metabolic Complications in Obesity: a Review. AB - Obese subjects are often characterized by low plasma 25-hydroxy-vitamin D (25OHD) levels. Many explanations for this association have been proposed. Low plasma 25OHD is associated with obesity-related comorbidities such as insulin resistance, type 2 diabetes mellitus, and low-grade inflammation. In this review, we discuss the proposed mechanisms for low 25OHD in obesity and explore the results of recent RCTs on vitamin D (VD) supplementation on obesity and its metabolic complications such as insulin resistance and type 2 diabetes. Although the results from these clinical randomized controlled trials vary, the general picture is that VD treatment of obese individuals does not seem to be an effective treatment of obesity-related metabolic complications. PMID- 26353883 TI - CCR5-CCL Axis in PDL during Orthodontic Biophysical Force Application. AB - Tooth movement by application of orthodontic biophysical force primarily reflects the role of soluble molecules released from the periodontal ligament (PDL). Thus far, many factors have been reported to be involved in orthodontic tooth movement (OTM), but key molecules that orchestrate responses of periodontal tissues to biophysical force are still enigmatic. In this in vivo study, in which the upper first molars in rats were moved, differential display-polymerase chain reaction revealed that CC chemokine receptor 5 (CCR5) level was differentially increased during OTM. Strong immunoreactivity for CCR5 was found in the PDL undergoing force application. Moreover, the in vitro compression or tension force application to primary cultured human PDL cells increased the expression of CCR5 and CCR5 ligands. In vitro tension force on human PDL cells did not induce RANKL, an osteoclastogenesis-inducing factor, but did induce the upregulation of IL12, an osteoclast inhibitory factor, and osteoblast differentiation factors, including Runx2, which was attenuated under tension by CCR5 gene silencing whereas augmented with CCR5 ligands. In contrast, in vitro compression force did not induce the expression of osteoprotegerin, a decoy receptor for RANKL and Runx2, but did induce the upregulation of RANKL, which was attenuated under compression by CCR5 gene silencing. These results suggest that the CCR5-CCR5 ligands axis in PDL cells may play a crucial role in the remodeling of periodontal tissues and can be a therapeutic target for achieving efficient OTM. PMID- 26353884 TI - HPV Infection of the Head and Neck Region and Its Stem Cells. AB - The human papillomavirus (HPV) is an etiologic agent associated with the development of head and neck squamous carcinoma (HNSCC)-in particular, oropharyngeal squamous cell carcinoma. The HPV-positive HNSCC is characterized by genetic alterations, clinical progression, and therapeutic response, which are distinct from HPV-negative head and neck cancers, suggesting that virus associated tumors constitute a unique entity among head and neck cancers. Malignant stem cells, or cancer stem cells, are a subpopulation of tumor cells that self-renew, initiate new tumors upon transplantation, and are resistant to therapy, and their discovery has revealed novel effects of oncovirus infection in cancer. In this review, we provide a virus-centric view and novel insights into HPV-positive head and neck pathogenesis. We discuss the influence of cancer stem cells, HPV oncoproteins, altered molecular pathways, and mutations in cancer initiation and cancer progression. We compiled a catalogue of the mutations associated with HPV-positive HNSCC, which may be a useful resource for genomic based studies aiming to develop personalized therapies. We also explain recent changes in mass vaccination campaigns against HPV and the potential long-term impact of vaccinations on the prevention and treatment of HPV-positive head and neck cancers. PMID- 26353885 TI - Pulmonary scedosporiosis mimicking aspergilloma in an immunocompetent host: a case report and review of the literature. AB - A case of localized lung scedosporiosis is reported here that mimicked aspergilloma in an immunocompetent host. Through this case the importance of considering Scedosporium spp. in differential diagnosis of locally invasive lung infections and fungal ball is highlighted. As it is difficult to differentiate Scedosporium from Aspergillus on clinical grounds, microscopy, radiology and histopathology, this case is further emphasizing the significance of the definitive etiological characterization of Scedosporium through culture or molecular diagnostic tools. Accurate identification of Scedosporium, surgical resection and high-dose voriconazole has been associated with favorable outcome in most reported cases of scedosporiosis. PMID- 26353886 TI - Is dissection the only way to learn anatomy? Thoughts from students at a non dissecting based medical school. AB - Anatomical teaching has been centred around dissection for centuries. Generations of doctors have been initiated into the medical profession by cutting into their first cadavers. With the number of donor cadavers available decreasing and medical student numbers increasing, the emphasis placed on dissection has changed dramatically over the past 15 years. However, a solid appreciation of human anatomy is still a necessary part of understanding pathology and treatments. Therefore in light of these changes we ask, is dissection the only option? Or are there other options which students can undertake to develop anatomical knowledge? PMID- 26353887 TI - Educational outcomes of Helping Babies Breathe training at a community hospital in Honduras. AB - OBJECTIVES: Helping Babies Breathe is an evidence-based curriculum designed to teach basic neonatal resuscitation in low-resource countries. The purpose of this study was to evaluate the acquisition of knowledge and skills following this training and correlation of learner characteristics to performance in a Spanish speaking setting. METHODS: Thirty-one physicians and 39 nurses completed Helping Babies Breathe training at a Honduran community hospital. Trainee knowledge and skills were evaluated before and after the training using a multiple-choice questionnaire, bag-mask ventilation skills test, and two objective structured clinical exams (OSCEs). Linear mixed-effects models were used to analyze assessment scores pre- and post-training by profession (physician or nurse) while controlling for covariates. RESULTS: Helping Babies Breathe training resulted in significant increases in mean scores for the multiple-choice question test, bag mask ventilation skills test, and OSCE B. Time to initiation of effective bag mask ventilation decreased from a mean of 74.8 to 68.4 s. Despite this improvement in bag-mask ventilation, only 42 % of participants were able to initiate effective bag-mask ventilation within the Golden Minute. Although physicians scored higher on the pre-test multiple-choice questions and bag-mask ventilation, nurses demonstrated a greater mean difference in scores after training. OSCE B scores pre- and post-training increased similarly between professions. Nurses' and physicians' performance in simulation was not significantly different after the training. Assessment scores and course feedback indicated a need for more skills practice, particularly with bag-mask ventilation. CONCLUSIONS: When evaluated immediately after an initial workshop, Helping Babies Breathe training resulted in significant gains in neonatal resuscitation knowledge and skills. Following training, nurses, who commonly do not perform these skills in real-life situations, were able to perform at a similar level to physicians. Further studies are necessary to determine how to sustain this knowledge and skills over time, tailor the course to learner characteristics, and whether this training translates into improvements in clinical practice. PMID- 26353888 TI - Improving treatment and survival: a population-based study of current outcomes after a hepatic resection in patients with metastatic colorectal cancer. AB - BACKGROUND: Population-based studies historically report underutilization of a resection in patients with colorectal metastases to the liver. Recent data suggest limitations of the methods in the historical analysis. The present study examines trends in a hepatic resection and survival among Medicare recipients with hepatic metastases. METHODS: Medicare recipients with incident colorectal cancer diagnosed between 1991 and 2009 were identified in the SEER(Surveillance, Epidemiology and End Results)-Medicare dataset. Patients were stratified into historical (1991-2001) and current (2002-2009) cohorts. Analyses compared treatment, peri-operative outcomes and survival. RESULTS: Of 31.574 patients with metastatic colorectal cancer to the liver, 14,859 were in the current cohort treated after 2002 and 16,715 comprised the historical control group. The overall proportion treated with a hepatic resection increased significantly during the study period (P < 0.001) with pre/post change from 6.5% pre-2002 to 7.5% currently (P < 0.001). Over time, haemorrhagic and infectious complications declined (both P <= 0.047), but 30-day mortality was similar (3.5% versus 3.9%, P = 0.660). After adjusting for predictors of survival, the use of a hepatic resection [hazard ratio (HR) = 0.40, 95% confidence interval (CI): 0.38-0.42, P < 0.001] and treatment after 2002 (HR = 0.88, 95% CI: 0.86-0.90, P < 0.001) were associated with a reduced risk of death. CONCLUSIONS: Case identification using International Classification of Diseases, 9th Revision (ICD-9) codes is imperfect; however, comparison of trends over time suggests an improvement in multimodality therapy and survival in patients with colorectal metastases to the liver. PMID- 26353889 TI - Human spermatozoa and temperature: the elephant in the room. AB - Men are notable for low sperm production, relative to that of other large mammals, and often inferior morphology and motility of their spermatozoa. The extent to which temperature plays a role in this picture has been a moot point. However, animal experiments suggest that an increased scrotal temperature of approximately +4 degrees C brought by inguinal clothing has a negative impact on the germinal epithelium and on the epididymis in man. In two animal species with inguinal testes, their transposition to the abdomen, raising the testis temperature by a modest approximate 1.5 degrees C brought reduced sperm production and abnormalities of spermiogenesis (distorted sperm nuclei, shared acrosomes), a picture seen commonly in man alongside morphologically normal spermatids. Reflection of the scrotal epididymis to the abdomen in laboratory animals did not inhibit sperm maturation there, but the consequences of this for other epididymal parameters are mirrored in several features seen in man. In addition to the typically puny form of the human cauda, these include often rapid epididymal sperm transit, rapid capacitation in vitro, a poor sperm reserve (as reflected in the steep decline in sperm numbers in successive ejaculates), and not least, the cauda's failure to maintain the viability of spermatozoa there (reflected in both their mixed potential for motility and the negative outcome of abstinence). Because the number of competent spermatozoa inseminated relates to prompt fertilization and/or incidence of pregnancy in some animal models, the negative effects of scrotal temperature may be an important factor in the need for an average of approximately five cycles of unprotected intercourse in order to establish pregnancy in human females. PMID- 26353890 TI - Riding the wave: determining the hierarchy of ovarian follicle activation. PMID- 26353891 TI - Global transcriptomic profiling of bovine endometrial immune response in vitro. I. Effect of lipopolysaccharide on innate immunity. AB - The dysregulation of endometrial immune response to bacterial lipopolysaccharide (LPS) has been implicated in uterine disease and infertility in the postpartum dairy cow, although the mechanisms are not clear. Here, we investigated whole transcriptomic gene expression in primary cultures of mixed bovine epithelial and stromal endometrial cells. Cultures were exposed to LPS for 6 h, and cellular response was measured by bovine microarray. Approximately 30% of the 1006 genes altered by LPS were classified as being involved in immune response. Cytokines and chemokines (IL1A, CX3CL1, CXCL2, and CCL5), interferon (IFN)-stimulated genes (RSAD2, MX2, OAS1, ISG15, and BST2), and the acute phase molecule SAA3 were the most up-regulated genes. Ingenuity Pathway Analysis identified up-regulation of many inflammatory cytokines and chemokines, which function to attract immune cells to the endometrium, together with vascular adhesion molecules and matrix metalloproteinases, which can facilitate immune cell migration from the tissue toward the uterine lumen. Increased expression of many IFN-signaling genes, immunoproteasomes, guanylate-binding proteins, and genes involved in the intracellular recognition of pathogens suggests important roles for these molecules in the innate defense against bacterial infections. Our findings confirmed the important role of endometrial cells in uterine innate immunity, whereas the global approach used identified several novel immune response pathways triggered by LPS in the endometrium. Additionally, many genes involved in endometrial response to the conceptus in early pregnancy were also altered by LPS, suggesting one mechanism whereby an ongoing response to infection may interfere with the establishment of pregnancy. PMID- 26353892 TI - Global transcriptomic profiling of bovine endometrial immune response in vitro. II. Effect of bovine viral diarrhea virus on the endometrial response to lipopolysaccharide. AB - Infection with noncytopathic bovine viral diarrhea virus (ncpBVDV) is associated with uterine disease and infertility. This study investigated the influence of ncpBVDV on immune functions of the bovine endometrium by testing the response to bacterial lipopolysaccharide (LPS). Primary cultures of mixed epithelial and stromal cells were divided into four treatment groups (control [CONT], BVDV, CONT+LPS, and BVDV+LPS) and infected with ncpBVDV for 4 days followed by treatment with LPS for 6 h. Whole-transcriptomic gene expression was measured followed by Ingenuity Pathway Analysis. Differential expression of 184 genes was found between CONT and BVDV treatments, showing interplay between induction and inhibition of responses. Up-regulation of TLR3, complement, and chemotactic and TRIM factors by ncpBVDV all suggested an ongoing immune response to viral infection. Down-regulation of inflammatory cytokines, chemokines, CXCR4, and serine proteinase inhibitors suggested mechanisms by which ncpBVDV may simultaneously counter the host response. Comparison between BVDV+LPS and CONT+LPS treatments showed 218 differentially expressed genes. Canonical pathway analysis identified the key importance of interferon signaling. Top down regulated genes were RSAD2, ISG15, BST2, MX2, OAS1, USP18, IFIT3, IFI27, SAMD9, IFIT1, and DDX58, whereas TRIM56, C3, and OLFML1 were most up-regulated. Many of these genes are also regulated by IFNT during maternal recognition of pregnancy. Many innate immune genes that typically respond to LPS were inhibited by ncpBVDV, including those involved in pathogen recognition, inflammation, interferon response, chemokines, tissue remodeling, cell migration, and cell death/survival. Infection with ncpBVDV can thus compromise immune function and pregnancy recognition, thereby potentially predisposing infected cows to postpartum bacterial endometritis and reduced fertility. PMID- 26353893 TI - Maternal SIN3A regulates reprogramming of gene expression during mouse preimplantation development. AB - The oocyte-to-embryo transition entails genome activation and a dramatic reprogramming of gene expression that is required for continued development. Superimposed on genome activation and reprogramming is development of a transcriptionally repressive state at the level of chromatin structure. Inducing global histone hyperacetylation relieves this repression and histone deacetylases 1 and 2 (HDAC1 and HDAC2) are involved in establishing the repressive state. Because SIN3A is an HDAC1/2-containing complex, we investigated whether it is involved in reprogramming gene expression during the course of genome activation. We find that Sin3a mRNA is recruited during maturation and that inhibiting its recruitment not only inhibits development beyond the 2-cell stage but also compromises the fidelity of reprogramming gene expression. The SIN3A that is synthesized during oocyte maturation reaches a maximum level in the mid-1-cell embryo and is essentially absent by the mid-2-cell stage. Overexpressing SIN3A in 1-cell embryos has no obvious effect on pre- and postimplantation development. These results provide a mechanism by which reprogramming can occur using a maternally inherited transcription machinery, namely, recruitment of mRNAs encoding transcription factors and chromatin remodelers, such as SIN3A. PMID- 26353894 TI - Human placenta-derived multipotent mesenchymal stromal cells involved in placental angiogenesis via the PDGF-BB and STAT3 pathways. AB - We studied the smooth muscle cell differentiation capability of human placental multipotent mesenchymal stromal cells (hPMSCs) and identified how endothelial cells recruit hPMSCs participating in vessel formation. hPMSCs from term placentas were induced to differentiate into smooth muscle cells under induction conditions and different matrix substrates. We assessed endothelial cells from umbilical veins for platelet-derived growth factor (PDGF)-BB expression and to induce hPMSC PDGFR-beta and STAT3 activation. Endothelial cells were co-cultured with hPMSCs for in vitro angiogenesis. Cell differentiation ability was then further assessed by mouse placenta transplantation assay. hPMSCs can differentiate into smooth muscle cells; collagen type I and IV or laminin support this differentiation. Endothelial cells expressed significant levels of PDGF-BB and activated STAT3 transcriptional activity in hPMSCs. Endothelial cell conditioned medium induced hPMSC migration, which was inhibited by STAT3 small interfering RNA transfection or by pretreatement with PDGFR-beta-blocking antibody but not by PDGFR-alpha-blocking antibody or isotype immunoglobulin G (IgG; P < 0.001). hPMSCs can incorporate into endothelial cells with tube formation and promote endothelial cells, forming capillary-like networks than endothelial cells alone (tube lengths: 12 024.1 +/- 960.1 vs. 9404.2 +/- 584.7 pixels; P < 0.001). Capillary-like networks were significantly reduced by hPMSCs pretreated with PDGFR-beta-blocking antibody but not by PDGFR-alpha-blocking antibody or isotype IgG (P < 0.001). Transplantation of hPMSCs into mouse placentas revealed incorporation of the hPMSCs into vessel walls, which expressed alpha-smooth muscle actin, calponin, and smooth muscle myosin (heavy chain) in vivo. In conclusion, endothelial cell-hPMSC interactions occur during vessel development of placenta. Placental endothelial cell-derived PDGF-BB recruits hPMSCs involved in vascular development via PDGFR-beta/STAT3 activation. PMID- 26353895 TI - Drug-Drug Interactions with the NS3/4A Protease Inhibitor Simeprevir. AB - Simeprevir is an NS3/4A protease inhibitor approved for the treatment of hepatitis C infection, as a component of combination therapy. Simeprevir is metabolized by the cytochrome P450 (CYP) system, primarily CYP3A, and is a substrate for several drug transporters, including the organic anion transporting polypeptides (OATPs). It is susceptible to metabolic drug-drug interactions with drugs that are moderate or strong CYP3A inhibitors (e.g. ritonavir and erythromycin) or CYP3A inducers (e.g. rifampin and efavirenz); coadministration of these drugs may increase or decrease plasma concentrations of simeprevir, respectively, and should be avoided. Clinical studies have shown that simeprevir is a mild inhibitor of CYP1A2 and intestinal CYP3A but does not inhibit hepatic CYP3A. The effects of simeprevir on these enzymes are of clinical relevance only for narrow-therapeutic-index drugs that are metabolized solely by these enzymes (e.g. oral midazolam). Simeprevir does not have a clinically relevant effect on the pharmacokinetics of rilpivirine, tacrolimus, oral contraceptives and several other drugs metabolized by CYP enzymes. Simeprevir is a substrate and inhibitor of the transporters P-glycoprotein (P-gp), breast cancer resistance protein (BCRP) and OATP1B1/3. Cyclosporine is an inhibitor of OATP1B1/3, BCRP and P-gp, and a mild inhibitor of CYP3A; cyclosporine causes a significant increase in simeprevir plasma concentrations, and coadministration is not recommended. Clinical studies have demonstrated increases in coadministered drug concentrations for drugs that are substrates of the OATP1B1/3, BRCP (e.g. rosuvastatin) and P-gp (e.g. digoxin) transporters; these drugs should be administered with dose titration and or/close monitoring. PMID- 26353896 TI - Large sample inference for a win ratio analysis of a composite outcome based on prioritized components. AB - Composite outcomes are common in clinical trials, especially for multiple time-to event outcomes (endpoints). The standard approach that uses the time to the first outcome event has important limitations. Several alternative approaches have been proposed to compare treatment versus control, including the proportion in favor of treatment and the win ratio. Herein, we construct tests of significance and confidence intervals in the context of composite outcomes based on prioritized components using the large sample distribution of certain multivariate multi sample U-statistics. This non-parametric approach provides a general inference for both the proportion in favor of treatment and the win ratio, and can be extended to stratified analyses and the comparison of more than two groups. The proposed methods are illustrated with time-to-event outcomes data from a clinical trial. PMID- 26353897 TI - Assessing the clinical utility of color Doppler ultrasound for ovarian torsion in the setting of a negative contrast-enhanced CT scan of the abdomen and pelvis. AB - PURPOSE: The purpose of this study is to evaluate the utility of color Doppler ultrasound (CDU) in the assessment of ovarian torsion following a negative contrast-enhanced computed tomography (CT) examination. METHODS: This is a retrospective study of women who presented to the ED with abdominal pain and received both a contrast-enhanced CT and CDU within a 24-h period. The abdominal/pelvic CT examinations were evaluated for findings specific to torsion, including ovarian size greater than 5 cm, the presence of free fluid, uterine deviation, fallopian tube thickening, ovarian fat stranding, smooth wall thickening, the presence of the "twisted pedicle" sign, and abnormal ovarian enhancement. The results were compared to the presence or absence of ovarian torsion on the concurrent US. RESULTS: The initial query yielded 834 cases among 789 women. Of those 834 cases, 283 cases in 261 women received both imaging modalities within a 24-h period. The CT examinations demonstrated 48 cases with an ovarian size greater than 5 cm. 84 cases showed the presence of free fluid. Three cases of fallopian tube thickening were identified. One case of smooth wall thickening and a "twisted pedicle" sign were noted. Fifteen cases demonstrated stranding of the peri-ovarian fat. Twenty nine cases showed abnormal ovarian enhancement. A total of 111 cases showed at least one positive finding. Fourteen positive cases were identified on the CDU studies. Of the 14 positive cases, 11 had ovarian size greater than 5 cm. Twelve cases demonstrated the presence of free fluid. There was no uterine deviation or smooth wall thickening. One twisted pedicle was noted. Seven cases showed peri-ovarian fat stranding. Ten cases showed abnormal enhancement. Abnormalities on CT were noted in all cases suspicious for ovarian torsion on CDU. No negative CT examinations were associated with a positive CDU. In this small sample size, the negative predictive value of a negative CT examination was 100%. CONCLUSION: A negative contrast-enhanced CT examination of the abdomen and pelvis is sufficient to rule out ovarian torsion. Therefore, there is no utility in the addition of CDU specifically to evaluate for ovarian torsion following a negative contrast enhanced CT scan of the abdomen and pelvis. PMID- 26353898 TI - Performance of tumor growth kinetics as an imaging biomarker for response assessment in colorectal liver metastases: correlation with FDG PET. AB - PURPOSE: To correlate RECIST, volumetric criteria, and tumor growth kinetics at multidetector-computed tomography with tumor metabolic activity at FDG PET in colorectal liver metastases (CRCLM) treated with bevacizumab-based chemotherapy. METHODS: Thirty-two CRCLM in 20 patients treated with bevacizumab-based chemotherapy were evaluated. Pre- and post-treatment CT scans were used to calculate reciprocal of doubling time (RDT), percentage change in the lesion's longest transaxial diameter (RECIST 1.1), and percentage change in the tumor volume. The accuracy of these parameters in predicting response based on standard uptake value analysis at FDG PET was assessed. Data were analyzed using Spearman's correlation, student's t, Mann-Whitney, Wilcoxon signed-rank, and Fisher's exact tests. RESULTS: According to FDG PET, 24/32 (75%) lesions were categorized as responders and 8/32 (25%) lesions as nonresponders. Based on RDT, 26/32 (81.25%) lesions were classified as responders and 6/32 (18.75%) lesions as nonresponders. Response classification according to RDT and FDG PET was concordant in 30/32 (93.75%) lesions, whereas RECIST 1.1 and volumetric criteria were concordant with FDG PET for 20/32 (62.5%) and 21/32 (65.63%) lesions, respectively. A strong association was found between RDT and response based on FDG PET (odds ratio = 127.4; 95% CI 5.54-2997; P < 0.0001). CONCLUSIONS: Tumor growth kinetics may be an effective imaging biomarker for response evaluation in CRCLM. PMID- 26353899 TI - Systolic Sac Pressure Index for the Prediction of Persistent Type II Endoleak for 12 Months After Endovascular Abdominal Aortic Aneurysm Repair. AB - PURPOSE: To assess the relationship between the systolic sac pressure index (SPI) and the presence of endoleaks 12 months after endovascular abdominal aortic aneurysm repair (EVAR). MATERIALS AND METHODS: We performed a single-center prospective trial of consecutively treated patients. SPI (calculated as systolic sac pressure/systolic aortic pressure) was measured by catheterization immediately after EVAR. Contrast-enhanced computed tomography was scheduled 12 months after EVAR to detect possible endoleaks. RESULTS: Data were available for 34 patients who underwent EVAR for an AAA. Persisting type II endoleak was found in 8 patients (endoleak-positive group) but not in the other 26 patients (endoleak-negative group). The mean +/- standard deviation SPI was significantly greater in the endoleak-positive group than in the endoleak-negative group (0.692 +/- 0.048 vs. 0.505 +/- 0.081, respectively; P = .001). Receiver-operating characteristic curve analysis revealed that an SPI of 0.638 was the optimum cutoff value for predicting a persistent endoleak at 12 months with high accuracy (0.971; 33/34), sensitivity (1.00), and specificity (0.962) values. The mean change in AAA diameter was -4.28 +/- 5.03 mm and 2.22 +/- 4.54 mm in patients with SPI of <0.638 or >=0.638, respectively (P = .002). CONCLUSION: Patients with an SPI of >=0.638 immediately after EVAR were more likely to have a persistent type II endoleak at 12 months with an accuracy of 0.971, and showed increases in aneurysm sac diameter compared with patients with an SPI of <0.638. PMID- 26353900 TI - Malignant Hilar Biliary Obstruction: Treatment by Means of Placement of a Newly Designed Y-Shaped Branched Covered Stent. AB - PURPOSE: To evaluate the technical feasibility and clinical efficacy of placement of a newly designed Y-shaped branched covered stent for palliative treatment of malignant hilar biliary obstruction. METHODS: From June 2011 to September 2014, 34 consecutive patients with malignant hilar biliary obstruction underwent percutaneous placement of a Y-shaped branched covered stent for palliative treatment. Technical and clinical success, complications, cumulative patient survival, and stent patency were evaluated. RESULTS: Stent placement was technically successful in all patients. All patients showed adequate biliary drainage on the follow-up cholangiogram. Mean serum bilirubin level (10.9 mg/dl) decreased significantly 1 week (5.7 mg/dl) and 1 month (2.6 mg/dl) after stent placement (p < 0.01). Complications associated with the procedure included hemobilia (n = 3) and biloma (n = 1). During the mean follow-up period of 225 (range 12-820) days, nine patients (26.5%) developed stent occlusion caused by tumor overgrowth (n = 8) and sludge (n = 1). Two of them underwent coaxial placement of a second stent with good results. The median survival time was 281 days and median primary stent patency was 337 days. There were no significant differences in the patient survival and stent patency rates in relation to age, sex, or Bismuth type. CONCLUSION: Percutaneous placement of the Y-shaped branched covered stent seems to be technically feasible and clinically effective for palliative treatment of malignant hilar biliary obstruction. PMID- 26353901 TI - Optimized extraction of polyphenolic antioxidant compounds from Brazil nut (Bertholletia excelsa) cake and evaluation of the polyphenol profile by HPLC. AB - BACKGROUND: The solid residue (cake) of pressed Brazil nut oil has high energy value and contains high levels of nutrients and bioactive compounds, such as polyphenols. However, little is known about these components in this by-product. Extraction is the first step in investigating the phenolic compounds in Brazil nut cake because extraction conditions might impact the yields of phenolic compounds and antioxidant capacity. The aim of this study was to select the best phenolic compound extraction conditions for Brazil nut cake by using factorial experimental design and to characterize the phenolic compounds in the extract. RESULTS: The optimal extraction of antioxidant phenolic compounds from Brazil nut cake was achieved under the following conditions: ethanol-water (40:60; v/v); 2.5 min homogenization; and 1 h extraction at 60 degrees C. The phenolic compound profile of the Brazil nut cake extract using the optimized extraction was determined by high-performance liquid chromatography with photodiode array detection. Six phenolic acids (gallic acid, protocatechuic acid, 2,4 dihydroxybenzoic acid, p-hydroxybenzoic acid, p-coumaric acid and sinapic acid) and one flavonoid ((+)-catechin) were identified, and the contents of the phenolic compounds varied from 70.0 to 421 mg kg(-1) . CONCLUSION: Knowledge of the potential bioactivity of Brazil nut cake identified in the present study might promote its use in the food industry. (c) 2015 Society of Chemical Industry. PMID- 26353902 TI - WILLINGNESS TO PAY FOR LUNG CANCER TREATMENT: PATIENT VERSUS GENERAL PUBLIC VALUES. AB - OBJECTIVES: Lung cancer has been the most common cancer since 1985, accounting for 12-13 percent of cancer cases worldwide. Newer targeted therapies with potential increased survival benefits may not be affordable to patients. Many countries use arbitrary thresholds to determine whether a medical intervention is cost-effective. As such, many effective, albeit expensive, therapies are not being reimbursed. To understand the value placed on effective therapies, this study evaluates the patient and public willingness to pay (WTP) for a quality adjusted life-year (QALY) for lung cancer treatments using Thailand as an example. METHODS: A total of 300 subjects responded to hypothetical lung cancer health states, described by three levels of severity and two levels of side effects, and provided their valuation of the level of quality of life and their WTP to improve from one state to another. RESULTS: The patients with the lowest income and general public were willing to pay more than twice the threshold for acceptability in Thailand (US Dollar 5,123/QALY [Thai Baht 160,000/QALY]). This increased significantly by wealth category. Patients' WTP was associated with quality of life, financial difficulties, health insurance, diarrhea, and wealth. CONCLUSIONS: The current study highlights the value patients and general public place on effective lung cancer therapies. PMID- 26353903 TI - Ability paradox of cascading model based on betweenness. AB - Must Investing more resources to protect every node in a network improve the robustness of the whole network subject to target attacks? To answer this question, we investigate the cascading dynamics in some typical networks. In real networks, the load on a node is generally correlated with the betweenness. Considering the weight of a node, we give a new method to define the initial load on a node by the revised betweenness. Then we present a simple cascading model. We investigate the cascading dynamics by disabling a single key node with the highest load. We find that in BA scale-free networks, the bigger the capacity of every node, the stronger the robustness of the whole network. However, in WS networks and some random networks, when we increase the capacity of every node, instead, the robustness of the whole network is weaker. In US power grid and the China power grid, we also observe this counterintuitive phenomenon. We give a reasonable explanation by a simple illusion. By the analysis, we think that resurrections of some nodes in a ring network structure after removing a node may be the reason of this phenomenon. PMID- 26353904 TI - Economic Impact of Alvimopan Considering Varying Definitions of Postoperative Ileus. AB - BACKGROUND: Prolonged postoperative ileus (POI) is the predominant cause of extended hospitalization after bowel resection surgery. Alvimopan accelerates gastrointestinal recovery, potentially reducing health care costs. We examined the value of alvimopan in reducing prolonged POI and length of stay for patients undergoing abdominal surgery using different definitions of POI. STUDY DESIGN: We developed a decision analytic model to examine costs and outcomes associated with postoperative treatment with either an accelerated care pathway (ACP) only or alvimopan+ACP. To represent an overall perspective for alvimopan, data from four phase 3 bowel resection trials and one phase 4 radical cystectomy trial were used to populate the model with 3 different definitions of POI. The period analyzed included start of surgery to 7 days post discharge. Costs were obtained from standard US costing sources and are reported in 2015 US dollars. Due to variations in published definitions of POI, alternative definitions based on adverse event reports, NG tube insertion, and time to food toleration were examined. RESULTS: The combined clinical trial data included 1,003 ACP and 1,013 alvimopan+ACP patients. When POI was reported as an adverse event, the incidence of POI was significantly lower with alvimopan+ACP (n = 70 [7%]) vs ACP alone (n = 148 [15%]; p < 0.0001). Time to discharge order written was shorter for patients with POI who were treated with alvimopan+ACP than with ACP (202 +/- 115 hours vs 266 +/- 138 hours; p < 0.0001). As a result, costs were $731 lower with alvimopan+ACP ($17,835) vs ACP ($18,566). Alternative definitions of POI produced similar results. CONCLUSIONS: The addition of alvimopan to existing treatment pathways for patients undergoing abdominal surgery can reduce overall hospital costs. PMID- 26353905 TI - Patients' and health professionals' understanding of and preferences for graphical presentation styles for individual-level EORTC QLQ-C30 scores. AB - PURPOSE: To investigate patients' and health professionals' understanding of and preferences for different graphical presentation styles for individual-level EORTC QLQ-C30 scores. METHODS: We recruited cancer patients (any treatment and diagnosis) in four European countries and health professionals in the Netherlands. Using a questionnaire, we assessed objective and self-rated understanding of QLQ-C30 scores and preferences for five presentation styles (bar and line charts, with or without color coding, and a heat map). RESULTS: In total, 548 patients and 227 health professionals participated. Eighty-three percent of patients and 85 % of professionals self-rated the graphs as very or quite easy to understand; this did not differ between graphical presentation styles. The mean percentage of correct answers to questions objectively assessing understanding was 59 % in patients, 78 % in medical specialists, and 74 % in other health professionals. Objective understanding did not differ between graphical formats in patients. For non-colored charts, 49.8 % of patients did not have a preference. Colored bar charts (39 %) were preferred over heat maps (20 %) and colored line charts (12 %). Medical specialists preferred heat maps (46 %) followed by non-colored bar charts (19 %), whereas these charts were equally valued by other health professionals (both 32 %). CONCLUSION: The substantial discrepancy between participants' high self-rated and relatively low objective understanding of graphical presentation of PRO results highlights the need to provide sufficient guidance when presenting such results. It may be appropriate to adapt the presentation of PRO results to individual preferences. This could be facilitated when PROs are administered and presented to patients and health professionals electronically. PMID- 26353906 TI - On the validity of measuring change over time in routine clinical assessment: a close examination of item-level response shifts in psychosomatic inpatients. AB - OBJECTIVE: Significant life events such as severe health status changes or intensive medical treatment often trigger response shifts in individuals that may hamper the comparison of measurements over time. Drawing from the Oort model, this study aims at detecting response shift at the item level in psychosomatic inpatients and evaluating its impact on the validity of comparing repeated measurements. STUDY DESIGN AND SETTING: Complete pretest and posttest data were available from 1188 patients who had filled out the ICD-10 Symptom Rating (ISR) scale at admission and discharge, on average 24 days after intake. Reconceptualization, reprioritization, and recalibration response shifts were explored applying tests of measurement invariance. In the item-level approach, all model parameters were constrained to be equal between pretest and posttest. If non-invariance was detected, these were linked to the different types of response shift. RESULTS: When constraining across-occasion model parameters, model fit worsened as indicated by a significant Satorra-Bentler Chi-square difference test suggesting potential presence of response shifts. A close examination revealed presence of two types of response shift, i.e., (non)uniform recalibration and both higher- and lower-level reconceptualization response shifts leading to four model adjustments. CONCLUSIONS: Our analyses suggest that psychosomatic inpatients experienced some response shifts during their hospital stay. According to the hierarchy of measurement invariance, however, only one of the detected non-invariances is critical for unbiased mean comparisons over time, which did not have a substantial impact on estimating change. Hence, the use of the ISR can be recommended for outcomes assessment in clinical routine, as change score estimates do not seem hampered by response shift effects. PMID- 26353907 TI - Evaluating PROMIS(r) instruments and methods for patient-centered outcomes research: Patient and provider voices in a substance use treatment setting. AB - PURPOSE: Our work as a primary research site of the Patient-Reported Outcomes Measurement Information System (PROMIS(r)), combined with support from the Patient-Centered Outcomes Research Institute, allowed us to evaluate the real world applicability and acceptability of PROMIS measures in an addiction medicine setting. METHODS: As part of a 3-month prospective observational study, 225 outpatients at a substance abuse treatment clinic completed PROMIS item banks for alcohol use (as well as 15 additional item banks from 8 other PROMIS domains, including emotional distress, sleep, and pain), with assessments at intake, 1 month follow-up, and 3-month follow-up. A subsample of therapists and their patients completed health domain importance ratings and qualitative interviews to elicit feedback regarding the content and format of the patients' assessment results. RESULTS: The importance ratings revealed that depression, anxiety, and lack of emotional support were rated highest of the non-alcohol-related domains among both patients and clinicians. General alcohol use was considered most important by both patients and clinicians. Based on their suggestions, changes were made to item response feedback to facilitate comprehension and communication. CONCLUSIONS: Both therapists and patients agreed that their review of the graphical display of scores, as well as individual item responses, helped them to identify areas of greatest concern and was useful for treatment planning. The results of our pilot work demonstrated the value and practicality of incorporating a comprehensive health assessment within a substance abuse treatment setting. PMID- 26353908 TI - Mental Health Problems Among Preschoolers in Germany: Results of the BELLA Preschool Study. AB - In a cross-sectional study, the prevalence rates of overall and specific mental health problems (MHP), as well as consequential impairments, were examined in a representative community sample of German preschoolers. MHP in 391 children were assessed by applying the Strength and Difficulties Questionnaire, as well as its impact supplement. Furthermore, the child behaviour checklist 11/2-5 (CBCL 11/2 5) and the IOWA-Conners behaviour rating scale were applied. Prevalence rates of MHP with 95 % confidence intervals (95 % CI) were determined. Odds ratios were calculated to analyse the relationships between MHP, age, gender, socioeconomic status, and geographical region using logistic regression. Overall, 7.4 % of the children showed symptoms of MHP. 12.9 % of the children were considered to be impaired by psychosocial problems. Depressive and anxiety symptoms were present in 4.2 % of the children; 11.8 % showed hyperactivity symptoms. The observed prevalence rates call for early mental health prevention in preschoolers. PMID- 26353909 TI - Global Gene Expression Profile of the Hippocampus in a Rat Model of Vascular Dementia. AB - Vascular dementia (VD) has been one of the most serious public health problems worldwide. It is well known that cerebral hypoperfusion is the key pathophysiological basis of VD, but it remains unclear how global genes in hippocampus respond to cerebral ischemia-reperfusion. In this study, we aimed to reveal the global gene expression profile in the hippocampus of VD using a rat model. VD was induced by repeated occlusion of common carotid arteries followed by reperfusion. The rats with VD were characterized by deficit of memory and cognitive function and by the histopathological changes in the hippocampus, such as a reduction in the number and the size of neurons accompanied by an increase in intercellular space. Microarray analysis of global genes displayed up regulation of 7 probesets with genes with fold change more than 1.5 (P < 0.05) and down-regulation of 13 probesets with genes with fold change less than 0.667 (P < 0.05) in the hippocampus. Gene Ontology (GO) and pathway analysis showed that the up-regulated genes are mainly involved in oxygen binding and transport, autoimmune response and inflammation, and that the down-regulated genes are related to glucose metabolism, autoimmune response and inflammation, and other biological process, related to memory and cognitive function. Thus, the abnormally expressed genes are closely related to oxygen transport, glucose metabolism, and autoimmune response. The current findings display global gene expression profile of the hippocampus in a rat model of VD, providing new insights into the molecular pathogenesis of VD. PMID- 26353910 TI - Mechanism of quinine-dependent monoclonal antibody binding to platelet glycoprotein IIb/IIIa. AB - Drug-dependent antibodies (DDAbs) that cause acute thrombocytopenia upon drug exposure are nonreactive in the absence of the drug but bind tightly to a platelet membrane glycoprotein, usually alpha(IIb)/beta3 integrin (GPIIb/IIIa) when the drug is present. How a drug promotes binding of antibody to its target is unknown and is difficult to study with human DDAbs, which are poly-specific and in limited supply. We addressed this question using quinine-dependent murine monoclonal antibodies (mAbs), which, in vitro and in vivo, closely mimic antibodies that cause thrombocytopenia in patients sensitive to quinine. Using surface plasmon resonance (SPR) analysis, we found that quinine binds with very high affinity (K(D) ~ 10-9 mol/L) to these mAbs at a molar ratio of ~ 2:1 but does not bind detectably to an irrelevant mAb. Also using SPR analysis, GPIIb/IIIa was found to bind monovalently to immobilized mAb with low affinity in the absence of quinine and with fivefold greater affinity (K(D) ~ 2.2 * 10-6) when quinine was present. Measurements of quinine-dependent binding of intact mAb and fragment antigen-binding (Fab) fragments to platelets showed that affinity is increased 10 000- to 100 000-fold by bivalent interaction between antibody and its target. Together, the findings indicate that the first step in drug-dependent binding of a DDAb is the interaction of the drug with antibody, rather than with antigen, as has been widely thought, where it induces structural changes that enhance the affinity/specificity of antibody for its target epitope. Bivalent binding may be essential for a DDAb to cause thrombocytopenia. PMID- 26353913 TI - Live births following karyomapping - a "key" milestone in the development of preimplantation genetic diagnosis. PMID- 26353912 TI - A new amino acid substitution (Ala-205-Phe) in acetolactate synthase (ALS) confers broad spectrum resistance to ALS-inhibiting herbicides. AB - MAIN CONCLUSION: This is a first report of an Ala-205-Phe substitution in acetolactate synthase conferring resistance to imidazolinone, sulfonylurea, triazolopyrimidines, sulfonylamino-carbonyl-triazolinones, and pyrimidinyl (thio) benzoate herbicides. Resistance to acetolactate synthase (ALS) and photosystem II inhibiting herbicides was confirmed in a population of allotetraploid annual bluegrass (Poa annua L.; POAAN-R3) selected from golf course turf in Tennessee. Genetic sequencing revealed that seven of eight POAAN-R3 plants had a point mutation in the psbA gene resulting in a known Ser-264-Gly substitution on the D1 protein. Whole plant testing confirmed that this substitution conferred resistance to simazine in POAAN-R3. Two homeologous forms of the ALS gene (ALSa and ALSb) were detected and expressed in all POAAN-R3 plants sequenced. The seven plants possessing the Ser-264-Gly mutation conferring resistance to simazine also had a homozygous Ala-205-Phe substitution on ALSb, caused by two nucleic acid substitutions in one codon. In vitro ALS activity assays with recombinant protein and whole plant testing confirmed that this Ala-205-Phe substitution conferred resistance to imidazolinone, sulfonylurea, triazolopyrimidines, sulfonylamino carbonyl- triazolinones, and pyrimidinyl (thio) benzoate herbicides. This is the first report of Ala-205-Phe mutation conferring wide spectrum resistance to ALS inhibiting herbicides. PMID- 26353911 TI - Morphological analysis of the 6b oncogene-induced enation syndrome. AB - MAIN CONCLUSION: The T-DNA 6b oncogene induces complex and partly unprecedented phenotypic changes in tobacco stems and leaves, which result from hypertrophy and hyperplasia with ectopic spot-like, ridge-like and sheet-like meristems. The Agrobacterium T-DNA oncogene 6b causes complex growth changes in tobacco including enations; this unusual phenotype has been called "6b enation syndrome". A detailed morphological and anatomical analysis of the aerial part of Nicotiana tabacum plants transformed with a dexamethasone-inducible dex-T-6b gene revealed several striking growth phenomena. Among these were: uniform growth of ectopic photosynthetic cells on the abaxial leaf side, gutter-like petioles with multiple parallel secondary veins, ectopic leaf primordia emerging behind large glandular trichomes, corniculate structures emerging from distal ends of secondary veins, pin-like structures with remarkable branching patterns, ectopic vascular strands in midveins and petioles extending down along the stem, epiascidia and hypoascidia, double enations and complete inhibition of leaf outgrowth. Ectopic stipule-like leaves and inverted leaves were found at the base of the petioles. Epinastic and hyponastic growth of petioles and midveins yielded complex but predictable leaf folding patterns. Detailed anatomical analysis of over sixty different 6b-induced morphological changes showed that the different modifications are derived from hypertrophy and abaxial hyperplasia, with ectopic photosynthetic cells forming spot-like, ridge-like and sheet-like meristems and ectopic vascular strands forming regular patterns in midveins, petioles and stems. Part of the enation syndrome is due to an unknown phloem-mobile enation factor. Graft experiments showed that the 6b mRNA is mobile and could be the enation factor. Our work provides a better insight in the basic effects of the 6b oncogene. PMID- 26353914 TI - Loss of G2 subunit of vacuolar-type proton transporting ATPase leads to G1 subunit upregulation in the brain. AB - Vacuolar-type ATPase (V-ATPase) is a primary proton pump with versatile functions in various tissues. In nerve cells, V-ATPase is required for accumulation of neurotransmitters into secretory vesicles and subsequent release at the synapse. Neurons express a specific isoform (G2) of the G subunit of V-ATPase constituting the catalytic sector of the enzyme complex. Using gene targeting, we generated a mouse lacking functional G2 (G2 null), which showed no apparent disorders in architecture and behavior. In the G2-null mouse brain, a G1 subunit isoform, which is ubiquitously expressed in neuronal and non-neuronal tissues, accumulated more abundantly than in wild-type animals. This G1 upregulation was not accompanied by an increase in mRNA. These results indicate that loss of function of neuron-specific G2 isoform was compensated by an increase in levels of the G1 isoform without apparent upregulation of the G1 mRNA. PMID- 26353915 TI - A Note on the Validity and Reliability of Multi-Criteria Decision Analysis for the Benefit-Risk Assessment of Medicines. AB - The comparative evaluation of benefits and risks is one of the most important tasks during the development, market authorization and post-approval pharmacovigilance of medicinal products. Multi-criteria decision analysis (MCDA) has been recommended to support decision making in the benefit-risk assessment (BRA) of medicines. This paper identifies challenges associated with bias or variability that practitioners may encounter in this field and presents solutions to overcome them. The inclusion of overlapping or preference-complementary criteria, which are frequent violations to the assumptions of this model, should be avoided. For each criterion, a value function translates the original outcomes into preference-related scores. Applying non-linear value functions to criteria defined as the risk of suffering a certain event during the study introduces specific risk behaviours in this prescriptive, rather than descriptive, model and is therefore a questionable practice. MCDA uses weights to compare the importance of the model criteria with each other; during their elicitation a frequent situation where (generally favourable) mild effects are directly traded off against low probabilities of suffering (generally unfavourable) severe effects during the study is known to lead to biased and variable weights and ought to be prevented. The way the outcomes are framed during the elicitation process, positively versus negatively for instance, may also lead to differences in the preference weights, warranting an appropriate justification during each implementation. Finally, extending the weighted-sum MCDA model into a fully inferential tool through a probabilistic sensitivity analysis is desirable. However, this task is troublesome and should not ignore that clinical trial endpoints generally are positively correlated. PMID- 26353916 TI - Singapore Chapter of Rheumatologists consensus statement on the eligibility for government subsidy of biologic disease modifying anti-rheumatic agents for the treatment of psoriatic arthritis. AB - AIM: In Singapore, patients with psoriatic arthritis (PsA) constitute a significant disease burden. There is good evidence for the efficacy of anti-tumor necrosis factor (anti-TNF) in PsA; however cost remains a limiting factor. Non biologic disease modifying anti-rheumatic drugs (nbDMARDs) hence remain the first line treatment option in PsA in spite of limited evidence. The Singapore Chapter of Rheumatologists aims to develop national guidelines for clinical eligibility for government-assisted funding of biologic disease modifying anti- rheumatic drugs (bDMARDs) for PsA patients in Singapore. METHODS: Evidence synthesis was performed by reviewing seven published guidelines on use of biologics for PsA. Using the modified Research and Development/University of California at Los Angeles Appropriateness Method (RAM), rheumatologists rated indications for therapies for different clinical scenarios. Points reflecting the output from the formal group consensus were used to formulate the practice recommendations. RESULTS: Ten recommendations were formulated relating to initiation, continuation and options of bDMARD therapy. The panellists agreed that a bDMARD is indicated if a patient has active PsA with at least five swollen and tender joints, digits or entheses and has failed two nbDMARD strategies at optimal doses for at least 3 months each. Any anti-TNF may be used and therapy may be continued if an adequate PsARC response is achieved by 3 months after commencement. CONCLUSION: The recommendations developed by a formal group consensus method may be useful for clinical practice and guiding funding decisions by relevant authorities in making bDMARD usage accessible and equitable to eligible patients in Singapore. PMID- 26353917 TI - Recent Trends in Copper-Catalyzed C-H Amination Routes to Biologically Important Nitrogen Scaffolds. AB - Nitrogen-containing heterocycles have found remarkable applications in natural product research, material sciences, and pharmaceuticals. Although the synthesis of this interesting class of compounds attracted the interest of generations of organic chemists, simple and straightforward assembly methods based on transition metal catalysis have regularly been elusive. The recent advancements in the development of C-H functionalization have helped in accomplishing the synthesis of a variety of complex heterocycles from simple precursors. This Focus Review summarizes the recent advances in one particular field: the copper-catalyzed C-N bond formation reactions via C-H bond functionalization to furnish a comprehensive range of nitrogen heterocycles. Applicability and synthetic feasibility of a particular reaction represent major requirements for the inclusion in this review. PMID- 26353918 TI - Purification and characterization of a Shigella conjugate vaccine, produced by glycoengineering Escherichia coli. AB - Shigellosis remains a major cause of diarrheal disease in developing countries and causes substantial morbidity and mortality in children. Glycoconjugate vaccines consisting of bacterial surface polysaccharides conjugated to carrier proteins are the most effective vaccines for controlling invasive bacterial infections. Nevertheless, the development of a multivalent conjugate vaccine to prevent Shigellosis has been hampered by the complex manufacturing process as the surface polysaccharide for each strain requires extraction, hydrolysis, chemical activation and conjugation to a carrier protein. The use of an innovative biosynthetic Escherichia coli glycosylation system substantially simplifies the production of glycoconjugates. Herein, the Shigella dysenteriae type 1 (Sd1) O polysaccharide is expressed and its functional assembly on an E. coli glycosyl carrier lipid is demonstrated by HPLC analysis and mass spectrometry. The polysaccharide is enzymatically conjugated to specific asparagine residues of the carrier protein by co-expression of the PglB oligosaccharyltransferase and the carrier protein exotoxin A (EPA) from Pseudomonas aeruginosa. The extraction and purification of the Shigella glycoconjugate (Sd1-EPA) and its detailed characterization by the use of physicochemical methods including NMR and mass spectrometry is described. The report shows for the first time that bioconjugation provides a newly developed and improved approach to produce an Sd1 glycoconjugate that can be characterized using state-of-the-art techniques. In addition, this generic process together with the analytical methods is ideally suited for the production of additional Shigella serotypes, allowing the development of a multivalent Shigella vaccine. PMID- 26353919 TI - Long-term outcomes of phakic patients with diabetic macular oedema treated with intravitreal fluocinolone acetonide (FAc) implants. PMID- 26353921 TI - Implementation research in emergency medicine: a systematic scoping review. AB - INTRODUCTION: Implementation research aims to increase the uptake of research findings into clinical practice to improve the quality of healthcare. This scoping systematic study aims to assess the volume and scope of implementation research in emergency medicine (EM) to obtain an overview and inform future implementation research. METHODS: Studies were identified by searching electronic databases and reference lists of included studies for the years 2002, 2007 and 2012. Titles/abstracts were screened, full papers checked and data extracted by one author, with a random sample checked by a second author. RESULTS: A total of 3581 citations were identified with 197 eligible papers included. The number of papers significantly increased over time from 26 in 2002 to 77 in 2007 and 94 in 2012 (p<0.05). Eighty-two (42%) focused on identifying evidence-practice gaps, 77 (39%) evaluated the effectiveness of implementation interventions and 38 (19%) explored barriers and enablers to change. Only two papers explicitly stated that theory was used. Five of the 77 effectiveness studies used a randomised design and few provided sufficient detail about the intervention undergoing evaluation. CONCLUSIONS: Although there was a significant increase in the number of implementation research papers, most studies focused on identifying evidence practice gaps or used weak study designs to evaluate the effects of implementation interventions. Recommendations for improving implementation research in EM include identifying barriers and enablers to implementation, using theory in areas where proven important gaps exist, improving the reporting of the content of interventions and using rigorous study designs to evaluate their effectiveness. PMID- 26353920 TI - Transdermal neuromodulation of noradrenergic activity suppresses psychophysiological and biochemical stress responses in humans. AB - We engineered a transdermal neuromodulation approach that targets peripheral (cranial and spinal) nerves and utilizes their afferent pathways as signaling conduits to influence brain function. We investigated the effects of this transdermal electrical neurosignaling (TEN) method on sympathetic physiology under different experimental conditions. The TEN method involved delivering high frequency pulsed electrical currents to ophthalmic and maxillary divisions of the right trigeminal nerve and cervical spinal nerve afferents. Under resting conditions, TEN significantly suppressed basal sympathetic tone compared to sham as indicated by functional infrared thermography of facial temperatures. In a different experiment, subjects treated with TEN reported significantly lower levels of tension and anxiety on the Profile of Mood States scale compared to sham. In a third experiment when subjects were experimentally stressed TEN produced a significant suppression of heart rate variability, galvanic skin conductance, and salivary alpha-amylase levels compared to sham. Collectively these observations demonstrate TEN can dampen basal sympathetic tone and attenuate sympathetic activity in response to acute stress induction. Our physiological and biochemical observations are consistent with the hypothesis that TEN modulates noradrenergic signaling to suppress sympathetic activity. We conclude that dampening sympathetic activity in such a manner represents a promising approach to managing daily stress. PMID- 26353922 TI - Central hepatectomy versus extended hepatectomy for liver malignancy: a matched cohort comparison. AB - OBJECTIVE: To compare surgical outcomes between matched central hepatectomy (CH) and extended hepatectomy (EH) groups. BACKGROUND: Surgical choices for centrally located liver tumours are limited. The traditional EH harbours substantial risks, whereas CH is an alternative parenchymal-sparing resection that may improve peri operative morbidity. METHODS: A review of 4661 liver resections at a single institution was performed. The cases (CH) were matched in a 1:1 ratio with EH controls. RESULTS: The CH group was matched for demographic, tumour and laboratory factors with either right EH or combined (right/left) EH groups (n = 63 per group). Colorectal liver metastases were the most common diagnosis occurring in 70% of the patients. Higher intra-operative blood loss was observed in the right EH(P = 0.01) and combined EH groups (P < 0.01) compared with the CH group. There was a trend towards lower 90-day morbidity in the CH group (43%) compared with the right EH(59%, P = 0.1) and combined EH groups (56%, P = 0.2). The length of hospital stay was significantly longer in the control groups (P < 0.01 for both). The control groups had significantly higher post-operative bilirubin and International Normalized Ratio (INR) levels compared with the CH group. A post-operative bilirubin higher than 4 mg/dl was observed in 2% of the CH group compared with 39% of the right EH group (P < 0.01) and 52% of the combined EH group (P < 0.01). No differences in the rates of bile leak/biloma, post-hepatectomy liver failure or 90-day mortality were found. CONCLUSIONS: CH, as compared with EH, was safe and associated with a shorter hospital stay and less post-operative liver dysfunction. CH should be considered in patients with centrally located tumours amenable to such a resection. PMID- 26353923 TI - Low-Temperature Solution-Processed Kesterite Solar Cell Based on in Situ Deposition of Ultrathin Absorber Layer. AB - The production of high-performance, solution-processed kesterite Cu2ZnSn(Sx,Se1 x)4 (CZTSSe) solar cells typically relies on high-temperature crystallization processes in chalcogen-containing atmosphere and often on the use of environmentally harmful solvents, which could hinder the widespread adoption of this technology. We report a method for processing selenium free Cu2ZnSnS4 (CZTS) solar cells based on a short annealing step at temperatures as low as 350 degrees C using a molecular based precursor, fully avoiding highly toxic solvents and high-temperature sulfurization. We show that a simple device structure consisting of ITO/CZTS/CdS/Al and comprising an extremely thin absorber layer (~110 nm) achieves a current density of 8.6 mA/cm(2). Over the course of 400 days under ambient conditions encapsulated devices retain close to 100% of their original efficiency. Using impedance spectroscopy and photoinduced charge carrier extraction by linearly increasing voltage (photo-CELIV), we demonstrate that reduced charge carrier mobility is one limiting parameter of low-temperature CZTS photovoltaics. These results may inform less energy demanding strategies for the production of CZTS optoelectronic layers compatible with large-scale processing techniques. PMID- 26353924 TI - Symptom profiles and explanatory models of first-episode psychosis in African-, Caribbean- and European-origin groups in Ontario. AB - AIM: To assess variability in symptom presentation and explanatory models of psychosis for people from different ethnic groups. METHODS: Clients with first episode psychosis (n = 171) who identified as black African, black Caribbean or white European were recruited from early intervention programmes in Toronto and Hamilton. We compared results by ethnic group for symptom profiles and explanatory models of illness. RESULTS: Clients of black Caribbean origin had a lower odds of reporting that they were speaking incomprehensibly (OR = 0.36; 95% CI: 0.14-0.90) and black African clients had a greater odds of reporting persistent aches or pains (OR = 2.92; 95% CI: 1.32-6.50). Black African clients had a lower odds of attributing the cause of psychosis to hereditary factors (OR = 0.41; 95% CI: 0.19-0.89) or to substance abuse (OR = 0.29; 95% CI: 0.13-0.67) and had a lower odds of assigning responsibility for their illness to themselves (OR = 0.41; 95% CI: 0.19-0.89). CONCLUSIONS: Understanding the differences in illness models for ethnic minority groups may help improve the cultural competence of mental health services. PMID- 26353925 TI - Sudden Cardiac Death Following Use of the Synthetic Cannabinoid MDMB-CHMICA. PMID- 26353926 TI - Multimodality Imaging Assessment of Prosthetic Heart Valves. AB - Echocardiography and fluoroscopy are the main techniques for prosthetic heart valve (PHV) evaluation, but because of specific limitations they may not identify the morphological substrate or the extent of PHV pathology. Cardiac computed tomography (CT) and magnetic resonance imaging (MRI) have emerged as new potential imaging modalities for valve prostheses. We present an overview of the possibilities and pitfalls of CT and MRI for PHV assessment based on a systematic literature review of all experimental and patient studies. For this, a comprehensive systematic search was performed in PubMed and Embase on March 24, 2015, containing CT/MRI and PHV synonyms. Our final selection yielded 82 articles on surgical valves. CT allowed adequate assessment of most modern PHVs and complemented echocardiography in detecting the obstruction cause (pannus or thrombus), bioprosthesis calcifications, and endocarditis extent (valve dehiscence and pseudoaneurysms). No clear advantage over echocardiography was found for the detection of vegetations or periprosthetic regurgitation. Whereas MRI metal artifacts may preclude direct prosthesis analysis, MRI provided information on PHV-related flow patterns and velocities. MRI demonstrated abnormal asymmetrical flow patterns in PHV obstruction and allowed prosthetic regurgitation assessment. Hence, CT shows great clinical relevance as a complementary imaging tool for the diagnostic work-up of patients with suspected PHV obstruction and endocarditis. MRI shows potential for functional PHV assessment although more studies are required to provide diagnostic reference values to allow discrimination of normal from pathological conditions. PMID- 26353927 TI - The prevalence and effective factors of crash helmet usage among motorcyclists in Iran. AB - BACKGROUND: Crash helmet plays an important role in protecting the deriver's head during crashes and reduces the rate of severe injuries and fatalities. Although it has been proved that wearing the crash helmet can save the deriver's life by around 42%; previous studies showed that the rate of wearing crash helmet has not been acceptable in Iran. Due to the huge number of motorcyclists on the roads in Iran, the use of crash helmet is an important area of research. The aim of this study was to assess the factors that could possibly relate to or affect the use of crash helmet by the motorcyclists. METHODS: This is an observational study on 414 motorcyclists in Shiraz, Southern Iran. All participants completed a questioner containing demographic features, crash helmet use, motorcycle license, and the reasons for using motorcycles. RESULTS: All the participants were males and aged from 16 to 64 years with mean age 27+/-9.28. The results of logistic regression model revealed that only the drivers who had motorcycle license (OR=2.73, C.I: 1.40-7.24), employed the motorcycle for reasons other than pleasure (OR=3.18, C.I: 1.42-7.37) and been driving for 10 or more years (OR=1.92 95% C.I: 1.12-3.30) had greater rate of wearing crash helmet. Interestingly, educational levels, age, and other demographical variables had no relationship with crash helmet usage. CONCLUSIONS: It is believed that in order to increase the rate of crash helmet use, it is necessary to enact obligatory requirement for driving license by motorcyclists and increase the legal age for motorcycle driving. PMID- 26353928 TI - Genome-wide RNAi analysis reveals that simultaneous inhibition of specific mevalonate pathway genes potentiates tumor cell death. AB - The mevalonate (MVA) pathway is often dysregulated or overexpressed in many cancers suggesting tumor dependency on this classic metabolic pathway. Statins, which target the rate-limiting enzyme of this pathway, 3-hydroxy-3-methylglutaryl CoA reductase (HMGCR), are promising agents currently being evaluated in clinical trials for anti-cancer efficacy. To uncover novel targets that potentiate statin induced apoptosis when knocked down, we carried out a pooled genome-wide short hairpin RNA (shRNA) screen. Genes of the MVA pathway were amongst the top-scoring targets, including sterol regulatory element binding transcription factor 2 (SREBP2), 3-hydroxy-3-methylglutaryl-coenzyme A synthase 1 (HMGCS1) and geranylgeranyl diphosphate synthase 1 (GGPS1). Each gene was independently validated and shown to significantly sensitize A549 cells to statin-induced apoptosis when knocked down. SREBP2 knockdown in lung and breast cancer cells completely abrogated the fluvastatin-induced upregulation of sterol-responsive genes HMGCR and HMGCS1. Knockdown of SREBP2 alone did not affect three dimensional growth of lung and breast cancer cells, yet in combination with fluvastatin cell growth was disrupted. Taken together, these results show that directly targeting multiple levels of the MVA pathway, including blocking the sterol-feedback loop initiated by statin treatment, is an effective and targetable anti-tumor strategy. PMID- 26353929 TI - Genome-wide analysis of DNA methylation and gene expression patterns in purified, uncultured human liver cells and activated hepatic stellate cells. AB - BACKGROUND & AIMS: Liver fibrogenesis - scarring of the liver that can lead to cirrhosis and liver cancer - is characterized by hepatocyte impairment, capillarization of liver sinusoidal endothelial cells (LSECs) and hepatic stellate cell (HSC) activation. To date, the molecular determinants of a healthy human liver cell phenotype remain largely uncharacterized. Here, we assess the transcriptome and the genome-wide promoter methylome specific for purified, non cultured human hepatocytes, LSECs and HSCs, and investigate the nature of epigenetic changes accompanying transcriptional changes associated with activation of HSCs. MATERIAL AND METHODS: Gene expression profile and promoter methylome of purified, uncultured human liver cells and culture-activated HSCs were respectively determined using Affymetrix HG-U219 genechips and by methylated DNA immunoprecipitation coupled to promoter array hybridization. Histone modification patterns were assessed at the single-gene level by chromatin immunoprecipitation and quantitative PCR. RESULTS: We unveil a DNA-methylation based epigenetic relationship between hepatocytes, LSECs and HSCs despite their distinct ontogeny. We show that liver cell type-specific DNA methylation targets early developmental and differentiation-associated functions. Integrative analysis of promoter methylome and transcriptome reveals partial concordance between DNA methylation and transcriptional changes associated with human HSC activation. Further, we identify concordant histone methylation and acetylation changes in the promoter and putative novel enhancer elements of genes involved in liver fibrosis. CONCLUSIONS: Our study provides the first epigenetic blueprint of three distinct freshly isolated, human hepatic cell types and of epigenetic changes elicited upon HSC activation. PMID- 26353930 TI - H19 non coding RNA-derived miR-675 enhances tumorigenesis and metastasis of breast cancer cells by downregulating c-Cbl and Cbl-b. AB - H19 is a long non-coding RNA precursor of miR-675 microRNA. H19 is increasingly described to play key roles in the progression and metastasis of cancers from different tissue origins. We have previously shown that the H19 gene is activated by growth factors and increases breast cancer cell invasion. In this study, we established H19/miR-675 ectopic expression models of MDA-MB-231 breast cancer cells to further investigate the underlying mechanisms of H19 oncogenic action. We showed that overexpression of H19/miR-675 enhanced the aggressive phenotype of breast cancer cells including increased cell proliferation and migration in vitro, and increased tumor growth and metastasis in vivo. Moreover, we identified ubiquitin ligase E3 family (c-Cbl and Cbl-b) as direct targets of miR-675 in breast cancer cells. Using a luciferase assay, we demonstrated that H19, through its microRNA, decreased both c-Cbl and Cbl-b expression in all breast cancer cell lines tested. Thus, by directly binding c-Cbl and Cbl-b mRNA, miR-675 increased the stability and the activation of EGFR and c-Met, leading to sustained activation of Akt and Erk as well as enhanced cell proliferation and migration. Our data describe a novel mechanism of protumoral action of H19 in breast cancer. PMID- 26353931 TI - TAK1 and IKK2, novel mediators of SCF-induced signaling and potential targets for c-Kit-driven diseases. AB - NF-kappaB activation depends on the IKK complex consisting of the catalytically active IKK1 and 2 subunits and the scaffold protein NEMO. Hitherto, IKK2 activation has always been associated with IkappaBalpha degradation, NF-kappaB activation, and cytokine production. In contrast, we found that in SCF-stimulated primary bone marrow-derived mast cells (BMMCs), IKK2 is alternatively activated. Mechanistically, activated TAK1 mediates the association between c-Kit and IKK2 and therefore facilitates the Lyn-dependent IKK2 activation which suffices to mediate mitogenic signaling but, surprisingly, does not result in NF-kappaB activation. Moreover, the c-Kit-mediated and Lyn-dependent IKK2 activation is targeted by MyD88-dependent pathways leading to enhanced IKK2 activation and therefore to potentiated effector functions. In neoplastic cells, expressing constitutively active c-Kit mutants, activated TAK1 and IKKs do also not induce NF-kappaB activation but mediate uncontrolled proliferation, resistance to apoptosis and enables IL-33 to mediate c-Kit-dependent signaling. Together, we identified the formation of the c-Kit-Lyn-TAK1 signalosome which mediates IKK2 activation. Unexpectedly, this IKK activation is uncoupled from the NF-kappaB machinery but is critical to modulate functional cell responses in primary-, and mediates uncontrolled proliferation and survival of tumor-mast cells. Therefore, targeting TAK1 and IKKs might be a novel approach to treat c-Kit-driven diseases. PMID- 26353932 TI - Base excision repair-mediated resistance to cisplatin in KRAS(G12C) mutant NSCLC cells. AB - KRAS mutations in NSCLC are supposed to indicate a poor prognosis and poor response to anticancer treatments but this feature lacks a mechanistic basis so far. In tumors, KRAS was found to be mutated mostly at codons 12 and 13 and a pool of mutations differing in the base alteration and the amino acid substitution have been described. The different KRAS mutations may differently impact on cancerogenesis and drug sensitivity. On this basis, we hypothesized that a different KRAS mutational status in NSCLC patients determines a different profile in the tumor response to treatments. In this paper, isogenic NSCLC cell clones expressing mutated forms of KRAS were used to determine the response to cisplatin, the main drug used in the clinic against NSCLC. Cells expressing the KRAS(G12C) mutation were found to be less sensitive to treatment both in vitro and in vivo. Systematic analysis of drug uptake, DNA adduct formation and DNA damage responses implicated in cisplatin adducts removal revealed that the KRAS(G12C) mutation might be particular because it stimulates Base Excision Repair to rapidly remove platinum from DNA even before the formation of cross links. The presented results suggest a different pattern of sensitivity/resistance to cisplatin depending on the KRAS mutational status and these data might provide proof of principle for further investigations on the role of the KRAS status as a predictor of NSCLC response. PMID- 26353934 TI - Visible light functioning photocatalyst based on Al2O3 doped Mn3O4 nanomaterial for the degradation of organic toxin. AB - Al2O3 doped Mn3O4 nanomaterial was synthesized by low-temperature stirring method and applied as a catalyst for the degradation of organic pollutants under solar light for prospective environmental applications. The morphological and physiochemical structure of the synthesized solar photocatalyst was investigated by X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), energy-dispersive spectroscopy (EDS), Fourier transform infrared spectroscopy (FT IR), and X-ray photoelectron spectroscopy (XPS). FESEM showed a mixture of nanowires and aggregated nanoparticles. This Al2O3 doped Mn3O4 nanomaterial exhibited high solar photocatalytic degradation in a short time when applied to brilliant cresyl blue (BCB). Thus, the synthesized nanoparticles can be used as an efficient solar photocatalyst for the degradation of BCB. PMID- 26353933 TI - Vav1: A Dr. Jekyll and Mr. Hyde protein--good for the hematopoietic system, bad for cancer. AB - Many deregulated signal transducer proteins are involved in various cancers at numerous stages of tumor development. One of these, Vav1, is normally expressed exclusively in the hematopoietic system, where it functions as a specific GDP/GTP nucleotide exchange factor (GEF), strictly regulated by tyrosine phosphorylation. Vav was first identified in an NIH3T3 screen for oncogenes. Although the oncogenic form of Vav1 identified in the screen has not been detected in clinical human tumors, its wild-type form has recently been implicated in mammalian malignancies, including neuroblastoma, melanoma, pancreatic, lung and breast cancers, and B-cell chronic lymphocytic leukemia. In addition, it was recently identified as a mutated gene in human cancers of various origins. However, the activity and contribution to cancer of these Vav1 mutants is still unclear. This review addresses the physiological function of wild-type Vav1 and its activity as an oncogene in human cancer. It also discusses the novel mutations identified in Vav1 in various cancers and their potential contribution to cancer development as oncogenes or tumor suppressor genes. PMID- 26353935 TI - Normative Scores for Standard Neuropsychological Tests in the Oldest Old From the French Population-Based PAQUID Study. AB - There is an obvious lack of validated norms for elderly persons aged 85 and older for the large majority of the neuropsychological tests used in clinical practice. Yet this range of "oldest-old" individuals drastically increases worldwide and is the more likely to develop dementia. Providing clinicians validated and updated norms to accurately evaluate cognitive functioning in this population is an important issue in geriatrics. This study provides normative scores for 7 neuropsychological tests commonly used in clinical practice. Data were collected in a sample of 283 subjects aged 85 and older, included in the PAQUID study, a population-based cohort conducted in France. Normative scores were calculated according to 2 age ranges and 2 educational levels, and are presented in percentiles. The norms provided in the present study involve 7 tests that are widely used in the neuropsychological assessment of geriatrics populations and should be of help for clinicians. PMID- 26353936 TI - Recent Advances on the Total Syntheses of Communesin Alkaloids and Perophoramidine. AB - The communesin alkaloids are a diverse family of Penicillium-derived alkaloids. Their caged-polycyclic structure and intriguing biological profiles have made these natural products attractive targets for total synthesis. Similarly, the ascidian-derived alkaloid, perophoramidine, is structurally related to the communesins and has also become a popular target for total synthesis. This review serves to summarize the many elegant approaches that have been developed to access the communesin alkaloids and perophoramidine. Likewise, strategies to access the communesin ring system are reviewed. PMID- 26353937 TI - InbR, a TetR family regulator, binds with isoniazid and influences multidrug resistance in Mycobacterium bovis BCG. AB - Isoniazid (INH), an anti-tuberculosis (TB) drug, has been widely used for nearly 60 years. However, the pathway through which Mycobacterium tuberculosis responds INH remain largely unclear. In this study, we characterized a novel transcriptional factor, InbR, which is encoded by Rv0275c and belongs to the TetR family, that is directly responsive to INH. Disrupting inbR made mycobacteria more sensitive to INH, whereas overexpressing inbR decreased bacterial susceptibility to the drug. InbR could bind specifically to the upstream region of its own operon at two inverted repeats and act as an auto-repressor. Furthermore, InbR directly bind with INH, and the binding reduced InbR's DNA binding ability. Interestingly, susceptibilities were also changed by InbR for other anti-TB drugs, such as rifampin, implying that InbR may play a role in multi-drug resistance. Additionally, microarray analyses revealed a portion genes of the inbR regulon have similar expression patterns in inbR-overexpressing strain and INH-treated wild type strain, suggesting that these genes, for example iniBAC, may be responsible to the drug resistance of inbR-overexpressing strain. The regulation of these genes by InbR were further assessed by ChIP-seq assay. InbR may regulate multiple drug resistance of mycobacteria through the regulation of these genes. PMID- 26353938 TI - High frequencies of antibiotic resistance genes in infants' meconium and early fecal samples. AB - The gastrointestinal tract (GIT) microbiota has been identified as an important reservoir of antibiotic resistance genes (ARGs) that can be horizontally transferred to pathogenic species. Maternal GIT microbes can be transmitted to the offspring, and recent work indicates that such transfer starts before birth. We have used culture-independent genetic screenings to explore whether ARGs are already present in the meconium accumulated in the GIT during fetal life and in feces of 1-week-old infants. We have analyzed resistance to beta-lactam antibiotics (BLr) and tetracycline (Tcr), screening for a variety of genes conferring each. To evaluate whether ARGs could have been inherited by maternal transmission, we have screened perinatal fecal samples of the 1-week-old babies' mothers, as well as a mother-infant series including meconium, fecal samples collected through the infant's 1st year, maternal fecal samples and colostrum. Our results reveal a high prevalence of BLr and Tcr in both meconium and early fecal samples, implying that the GIT resistance reservoir starts to accumulate even before birth. We show that ARGs present in the mother may reach the meconium and colostrum and establish in the infant GIT, but also that some ARGs were likely acquired from other sources. Alarmingly, we identified in both meconium and 1-week-olds' samples a particularly elevated prevalence of mecA (>45%), six fold higher than that detected in the mothers. The mecA gene confers BLr to methicillin-resistant Staphylococcus aureus, and although its detection does not imply the presence of this pathogen, it does implicate the young infant's GIT as a noteworthy reservoir of this gene. PMID- 26353939 TI - A corneal elastic dynamic model derived from Scheimpflug imaging technology. AB - PURPOSE: To simultaneously extract the corneal Young's modulus and the damping ratio from Scheimpflug imaging data. METHODS: A spherical diaphragm model can better represent the geometry and physics of an eyeball than the popular mass spring-damper model. This research derived the dynamic model of a water-filled spherical diaphragm based on the hydrodynamics and wave propagation theories. By applying modal analysis on the model, one can decouple the cornea vibration into individual modes and reconstruct the air puff vibration from the decoupled responses. By matching this response with the Scheimpflug imaging data from the Corvis((r)) ST, it was then possible to extract multiple physiological properties as desired. RESULTS: The dynamic modal analysis was employed to extract the corneal physiological properties of 25 Taiwanese normal subjects. Specifically, the corneal Young's moduli and damping ratios were estimated. In fact the model is dependent on the physiological parameters such as cornea thickness, densities, and intraocular pressure. It is thus also possible to extract these parameters through multi-goal minimisation processes. CONCLUSIONS: The spherical diaphragm model was able to better describe the dynamic response of the eyeball. The model analysis also provides additional corneal physiological properties that were not available through other means. PMID- 26353941 TI - Do Results of Surveillance Cultures Impact the Choice of Empirical Antibiotics Among Patients with Carbapenem-Resistant Acinetobacter baumannii Infections? AB - We aimed to determine whether the results of surveillance cultures were associated with use of appropriate empirical antibiotic therapy among patients with carbapenem-resistant Acinetobacter baumannii infections. We found that surveillance status was not associated with appropriate empirical antibiotic therapy (P=.36). There were significant delays to concordant therapy among surveillance-positive patients (P=.03). PMID- 26353942 TI - Guided endodontics: accuracy of a novel method for guided access cavity preparation and root canal location. AB - AIM: To present a novel method utilizing 3D printed templates to gain guided access to root canals and to evaluate its accuracy in vitro. METHODOLOGY: Sixty extracted human teeth were placed into six maxillary jaw models. Preoperative CBCT scans were matched with intra-oral scans using the coDiagnostix(TM) software. Access cavities, sleeves and templates for guidance were virtually planned. Templates were produced by a 3D printer. After access cavity preparation by two operators, a postoperative CBCT scan was superimposed on the virtual planning. Accuracy was measured by calculating the deviation of planned and prepared cavities in three dimensions and angle. Ninety-five per cent confidence intervals were calculated for both operators. RESULTS: All root canals were accessible after cavity preparation with 'Guided Endodontics'. Deviations of planned and prepared access cavities were low with means ranging from 0.16 to 0.21 mm for different aspects at the base of the bur and 0.17-0.47 mm at the tip of the bur. Mean of angle deviation was 1.81 degrees . Overlapping 95% confidence intervals revealed no significant difference between operators. CONCLUSION: 'Guided Endodontics' allowed an accurate access cavity preparation up to the apical third of the root utilizing printed templates for guidance. All root canals were accessible after preparation. PMID- 26353940 TI - Blood coagulation protein fibrinogen promotes autoimmunity and demyelination via chemokine release and antigen presentation. AB - Autoimmunity and macrophage recruitment into the central nervous system (CNS) are critical determinants of neuroinflammatory diseases. However, the mechanisms that drive immunological responses targeted to the CNS remain largely unknown. Here we show that fibrinogen, a central blood coagulation protein deposited in the CNS after blood-brain barrier disruption, induces encephalitogenic adaptive immune responses and peripheral macrophage recruitment into the CNS leading to demyelination. Fibrinogen stimulates a unique transcriptional signature in CD11b(+) antigen-presenting cells inducing the recruitment and local CNS activation of myelin antigen-specific Th1 cells. Fibrinogen depletion reduces Th1 cells in the multiple sclerosis model, experimental autoimmune encephalomyelitis. Major histocompatibility complex (MHC) II-dependent antigen presentation, CXCL10- and CCL2-mediated recruitment of T cells and macrophages, respectively, are required for fibrinogen-induced encephalomyelitis. Inhibition of the fibrinogen receptor CD11b/CD18 protects from all immune and neuropathologic effects. Our results show that the final product of the coagulation cascade is a key determinant of CNS autoimmunity. PMID- 26353943 TI - Last hope for the doomed? Thoughts on the importance of a parasexual cycle for the yeast Candida albicans. AB - The yeast Candida albicans, a commensal colonizer and occasional pathogen of humans, has a rudimentary mating ability. However, mating is a cumbersome process that has never been observed outside the laboratory, and the population structure of the species is predominantly clonal. Here we discuss recent findings that indicate that mating ability is under selection in C. albicans, i.e. that it is a biologically relevant process. C. albicans strains can only mate after they have sustained genetic damage. We propose that the rescue of such damaged strains by mating may be the primary reason why mating ability is under selection. PMID- 26353944 TI - Commentary on 'Hemothorax Management After Endovascular Treatment For Thoracic Aortic Rupture'. PMID- 26353945 TI - Skin involvement in Dupuytren's disease. AB - Whether the palmar skin has a role in the development, propagation or recurrence of Dupuytren's disease remains unclear. Clinical assessment for skin involvement is difficult and its correlation with histology uncertain. We prospectively biopsied the palmar skin of consecutive patients undergoing single digit fasciectomy (for primary Dupuytren's disease without clinically involved skin) and dermofasciectomy (for clinically involved skin or recurrence) in order to investigate this relationship. We found dermal fibromatosis in 22 of 44 patients (50%) undergoing fasciectomy and 41 of 59 patients (70%) undergoing dermofasciectomy. Dermal fibromatosis appeared to be associated with greater preoperative angular deformity, presence of palmar nodules and occupations involving manual labour. Dermal fibromatosis exists in the absence of clinical features of skin involvement and we hypothesize that the skin may have a greater role in the development and propagation of Dupuytren's disease than previously thought. LEVEL OF EVIDENCE: III. PMID- 26353946 TI - Comparison of short wrist transverse open and limited open techniques for carpal tunnel release: a randomized controlled trial of two incisions. AB - The purpose of this randomized controlled trial was to compare outcomes of limited open and short wrist transverse techniques in patients with carpal tunnel syndrome. In a single centre randomized controlled trial, 84 patients with idiopathic carpal tunnel syndrome were randomized before surgery to limited open or short wrist transverse open carpal tunnel release. The patients were evaluated at 6 weeks, 3 months, 6 months, and 1 and 2 years after surgery. At every follow up, the Brigham and Women's Carpal Tunnel Questionnaire scores, scar discomfort, and subjective patient satisfaction were evaluated. Two years after surgery, five patients were lost to follow-up. The groups had similar Brigham and Women's Carpal Tunnel Questionnaire Symptom Severity and Functional Status scores and subjective satisfaction scores. The incidence of scar discomfort was not significantly different between the two groups on serial postoperative follow-up. Short wrist transverse open release surgery showed similar early postoperative symptoms and subjective and functional outcomes to limited open release. LEVEL OF EVIDENCE: II. PMID- 26353947 TI - Metformin use and risk of prostate cancer: results from the REDUCE study. AB - The role of metformin in prostate cancer chemoprevention remains unclear. REDUCE, which followed biopsy-negative men with protocol-dictated PSA-independent biopsies at 2- and 4-years, provides an opportunity to evaluate the link between metformin use and prostate cancer diagnosis with minimal confounding from screening biases. In diabetic men from REDUCE, we tested the association between metformin use, use of other antidiabetic medications, versus no antidiabetic medication use, and prostate cancer diagnosis as well as prostate cancer grade (low-grade Gleason 4-6 and high-grade Gleason 7-10) using logistic regression. Of the 540 diabetic men with complete data, 205 (38%) did not report use of any antidiabetic medications, 141 (26%) reported use of at least one antidiabetic medication other than metformin, and 194 (36%) reported use of metformin. During the 4-year study, 122 men (23%) were diagnosed with prostate cancer. After adjusting for various clinical and demographic characteristics, we found that metformin use was not significantly associated with total (OR, 1.19; P = 0.50), low- (OR, 1.01; P = 0.96), or high-grade (OR, 1.83; P = 0.19) prostate cancer diagnosis. Likewise, there was no significant association between the use of non metformin antidiabetic medications and prostate cancer risk in both crude (OR, 1.02; P = 0.95) and multivariable analysis (OR, 0.85; P = 0.56). Furthermore, the interactions between antidiabetic medication use and BMI, geographic location, coronary artery disease, smoking, and treatment group were not significant (all P > 0.05). Among diabetic men with a negative prestudy biopsy who all underwent biopsies largely independent of PSA, metformin use was not associated with reduced risk of prostate cancer diagnosis. PMID- 26353948 TI - The FDA guidance on therapeutic cancer vaccines: the need for revision to include preventive cancer vaccines or for a new guidance dedicated to them. AB - Cancer vaccines based on antigens derived from self molecules rather than pathogens have been under basic and clinical investigations for many years. Up until very recently, they had been tested primarily in the setting of metastatic disease with the goal to engage the immune system in slowing down disease progression. Many therapeutic vaccine trials, either investigator initiated or led by pharmaceutical companies, have been completed and many are currently ongoing, following the FDA Guidance on therapeutic cancer vaccines published in 2011. In recent years, the target of cancer vaccines is being shifted to early cancer and even premalignant disease with the goal of preventing cancer. Although some issues addressed in the FDA Guidance on therapeutic vaccines apply to preventive vaccines, many do not. Here, we discuss a set of recommendations for revising the current Guidance to also cover preventive vaccines, or to include in a new Guidance dedicated specifically to vaccines for cancer prevention. PMID- 26353950 TI - "Cutting-Edge Analytical Chemistry Research by Women Scientists". PMID- 26353949 TI - Nitric oxide synthesis by nitrate reductase is regulated during development in Aspergillus. AB - Nitric oxide (NO) is a signalling molecule involved in many biological processes in bacteria, plants and mammals. However, little is known about the role and biosynthesis of NO in fungi. Here we show that NO production is increased at the early stages of the transition from vegetative growth to development in Aspergillus nidulans. Full NO production requires a functional nitrate reductase (NR) gene (niaD) that is upregulated upon induction of conidiation, even under N repressing conditions in the presence of ammonium. At this stage, NO homeostasis is achieved by balancing biosynthesis (NR) and catabolism (flavohaemoglobins). niaD and flavohaemoglobin fhbA are transiently upregulated upon induction of conidiation, and both regulators AreA and NirA are necessary for this transcriptional response. The second flavohaemoglobin gene fhbB shows a different expression profile being moderately expressed during the early stages of the transition phase from vegetative growth to conidiation, but it is strongly induced 24 h later. NO levels influence the balance between conidiation and sexual reproduction because artificial strong elevation of NO levels reduced conidiation and induced the formation of cleistothecia. The nitrate-independent and nitrogen metabolite repression-insensitive transcriptional upregulation of niaD during conidiation suggests a novel role for NR in linking metabolism and development. PMID- 26353951 TI - Microdevice in Cellular Pathology: Microfluidic Platforms for Fluorescence in situ Hybridization and Analysis of Circulating Tumor Cells. AB - Microfluidic devices enable the miniaturization, integration, automation, and parallelization of chemical and biochemical processes. This new technology also provides opportunity for expansion in the field of cellular pathology. Fluorescence in situ hybridization (FISH) is a well-known gene-based method to image genetic abnormalities. Development of a FISH microfluidic platform has offered the possibility of automation with significant time and cost reductions, which overcomes many drawbacks of the current protocols. Microfluidic devices are also powerful tools for single-cell analysis. Capturing the circulating tumor cells (CTCs) from blood samples is one of the most promising approaches to enable the early diagnosis of cancer. The microfluidic devices are also useful to isolate rare CTCs at high efficiency and purity. In this review, I outline recent FISH and CTC analyses using microfluidic devices, and describe their applications for the cellular diagnosis of cancers. PMID- 26353952 TI - On-chip FRET Graphene Oxide Aptasensor: Quantitative Evaluation of Enhanced Sensitivity by Aptamer with a Double-stranded DNA Spacer. AB - We propose a molecular design for a biomolecular probe to realize an on-chip graphene oxide (GO) aptasensor with enhanced sensitivity. Here, GO works as an excellent acceptor for fluorescence resonance energy transfer. We inserted a rigid double-stranded DNA as a spacer between the GO surface and the aptamer sequence to extend the distance between a fluorescence dye and the GO surface during molecular recognition. We examined the dependence of the sensitivity on the length of the spacer quantitatively by using a 2*2 linear-array aptasensor. We used the modified aptamer with 10 and 30 base pair (bp) double-stranded DNA spacers. The signal with a 30bp-spacer was about twice as strong that with a 10bp spacer as regards both thrombin and prostate specific antigen detections. The improvement in the sensitivity was supported by a model calculation that estimated the effect of spacer length on fluorescence recovery efficiency. PMID- 26353953 TI - Temperature-responsive Solid-phase Extraction Column for Biological Sample Pretreatment. AB - We have developed a novel solid-phase extraction (SPE) system utilizing a temperature-responsive polymer hydrogel-modified stationary phase. Aminopropyl silica beads (average diameter, 40 - 64 MUm) were coated with poly(N isopropylacrylamide) (PNIPAAm)-based thermo-responsive hydrogels. Butyl methacrylate (BMA) and N,N-dimethylaminopropyl acrylamide (DMAPAAm) were used as the hydrophobic and cationic monomers, respectively, and copolymerized with NIPAAm. To evaluate the use of this SPE cartridge for the analysis of drugs and proteins in biological fluids, we studied the separation of phenytoin and theophylline from human serum albumin (HSA) as a model system. The retention of the analytes in an exclusively aqueous eluent could be modulated by changing the temperature and salt content. These results indicated that this temperature responsive SPE system can be applied to the pretreatment of biological samples for the measurement of serum drug levels. PMID- 26353954 TI - Influence of Introduced Substituents on the Anion-selectivity of [14]Tetraazaannulene Complexes. AB - Nickel(II) complexes of [14]tetraazaannulene derivatives incorporating aromatic rings into their azaannulene framework were synthesized, and the anion selectivity of the [14]tetraazaannulene nickel complexes 1 - 4 was evaluated by potentiometric measurements with solvent polymeric membrane electrodes. All of the [14]Tetraazaannulene nickel complexes, except 3, were found to exhibit high selectivity for the I(-) ion over the SCN(-) ion, although considerable interference of the ClO4(-) ion was observed in all 1 - 4 complexes. Concerning the anion-selectivities of 1 and 4, the incorporation of naphthalene rings into the azaannulene framework decreased not only the interference of the ClO4(-) ion but also the I(-) ion-selectivity over the SCN(-) ion. Comparison studies between the dibenzotetraaza[14]annulene nickel complexes 1 - 3 indicated that differences in the attached substituents of the [14]tetraazaannulene nickel complexes greatly influenced the ion-selectivity as ionophores. According to our computational results, the ionophoric properties of [14]tetraazaannulene nickel complexes 1 - 4 were influenced by their electrostatic properties rather than their topological properties. PMID- 26353955 TI - Analysis of Intra- and Extracellular Levels of Purine Bases, Nucleosides, and Nucleotides in HepG2 Cells by High-performance Liquid Chromatography. AB - To evaluate cellular uptake and purine transport, we developed a high-performance liquid chromatography method for intra- and extracellular purine quantification. Our aim was to develop an effective method for simultaneously quantifying the substrate and metabolites with high sensitivity. C18 columns from different manufacturers were tested for simultaneous quantification of 22 different purine bases, nucleosides, and nucleotides. We used a YMC-Triart C18 column. The analysis conditions, including extraction solutions for the cells and cell culture medium, were optimized to achieve good quantification. Linearity, accuracy, determination limits, and recovery were assessed and showed good performance. The developed HPLC method was successfully applied to the qualitative analysis of 22 different intra- and extracellular purines, demonstrating that it is useful for studying the overall pattern of purine metabolism. This method could also be useful for evaluating metabolic dynamics of purines under a variety of stimulatory conditions of culture cells. PMID- 26353956 TI - Repeatability Assessment by ISO 11843-7 in Quantitative HPLC for Herbal Medicines. AB - We have proposed an assessment methods to estimate the measurement relative standard deviation (RSD) of chromatographic peaks in quantitative HPLC for herbal medicines by the methodology of ISO 11843 Part 7 (ISO 11843-7:2012), which provides detection limits stochastically. In quantitative HPLC with UV detection (HPLC-UV) of Scutellaria Radix for the determination of baicalin, the measurement RSD of baicalin by ISO 11843-7:2012 stochastically was within a 95% confidence interval of the statistically obtained RSD by repetitive measurements (n = 6). Thus, our findings show that it is applicable for estimating of the repeatability of HPLC-UV for determining baicalin without repeated measurements. In addition, the allowable limit of the "System repeatability" in "Liquid Chromatography" regulated in a pharmacopoeia can be obtained by the present assessment method. Moreover, the present assessment method was also successfully applied to estimate the measurement RSDs of quantitative three-channel liquid chromatography with electrochemical detection (LC-3ECD) of Chrysanthemi Flos for determining caffeoylquinic acids and flavonoids. By the present repeatability assessment method, reliable measurement RSD was obtained stochastically, and the experimental time was remarkably reduced. PMID- 26353957 TI - Generation Mechanism of Deferoxamine Radical by Tyrosine-Tyrosinase Reaction. AB - Nitroxide radical formations of deferoxamine mesylate (DFX) that is used clinically to treat iron-overload patients was examined by a tyrosine-tyrosinase reaction system as models of the H-atom transfer or proton-coupled electron transfer. When DFX was exposed to the tyrosine-tyrosinase reaction, nine-line ESR spectrum (g = 2.0063, hfcc; aN = 0.78 mT, aH(2) = 0.63 mT) was detected, indicating that the oxidation of DFX leads to a nitroxide radical. The signal intensity of the DFX radical increased dependently on the concentrations of tyrosine and tyrosinase. The amounts of DMPO-OH spin adducts via the tyrosine tyrosinase reaction declined with DFX. Furthermore, mass spectra of an extra removed from the tyrosine-tyrosinase reaction mixture showed that the enzyme reactions might not be degradations of DFX. Therefore, there might be two types of DFX reaction passways, which could be through an internal electron transfer from tyrosine and hydrogen absorptions by .OH directly. PMID- 26353958 TI - Coordination Chemistry of Europium(III) Ion Towards Acylpyrazolone Ligands. AB - Two Eu(III) complexes were synthesized using 4-acylpyrazolone ligands: 3-methyl-4 (4-methylbenzoyl)-1-phenyl-pyrazol-5-one (HPMMBP) and 3-methyl-1-phenyl-4-(4 phenylbenzoyl)-pyrazol-5-one (HPPMBP). The composition of the obtained solid complexes was determined as Eu(PMMBP)3.C2H5OH and Eu(PPMBP)3.3H2O based on elemental analysis and was further studied by IR, NMR and TG-TSC data. The lanthanoid complexation in solid state and in solution during liquid-liquid extraction (molecular diluent and ionic liquid) is discussed. PMID- 26353959 TI - A Fluorous Biphasic Solvent Extraction System for Lanthanides with a Fluorophilic beta-Diketone Type Extractant. AB - The properties of a fluorous solvent extraction system for trivalent lanthanide metal ions are reported. A fluorinated extractant, 4,4,5,5,6,6,7,7,8,8,9,9,9 tridecafluoro-1-(2-thienyl)-1,3-nonanedione, and HFE-7200 (C4F9OC2H5) as the extraction solvent were chosen. With this fluorous extractant/solvent combination, higher extraction ratios and separation factors compared to a conventional organic solvent system (thenoyltrifluoroacetone in CHCl3) were achieved for 5 heavy lanthanide ions (Lu, Yb, Tm, Er and Ho). On the other hand, light lanthanide ions (Nd, Pr, Ce and La) are hardly extracted, therefore enabling the mutual separation of light lanthanides from middle or heavy lanthanide ions. PMID- 26353960 TI - Analysis of Water State and Gelation of Methylcellulose Thermo-reversible Hydrogels by Thermal Analysis and NMR. AB - The gelation of aqueous methylcellulose (MC) solutions containing polyethylene glycol (PEG) was studied by the combination of differential scanning calorimetry (DSC) and Raman spectrometry. The gelation of MC hydrogels containing PEG occurred in two-steps. First, the gel network was formed by the hydrophobic interaction between MC and PEG at 310 - 313 K, and then, the gel network was formed between MC chains at 323 K. On the other hand, in the MC hydrogels containing PEG and NaCl, sodium ion assumed to be enclosed by PEG, forming a helix with the hydrophobic groups outward. The sodium ion in the gel was expected to be surrounded by the ether oxygen of PEG as crown ether. PMID- 26353961 TI - Proteomic Analysis after Sequential Extraction of Matrix Proteins in Urinary Stones Composed of Calcium Oxalate Monohydrate and Calcium Oxalate Dihydrate. AB - In this study, we performed proteomic analysis following sequential protein extraction on calcium oxalate monohydrate (COM) and calcium oxalate dihydrate (COD) urinary stones to determine the specific matrix proteins according to the crystal components of the stones. After X-ray and IR analysis of 13 urinary stones, matrix proteins were sequentially extracted with KCl, formic acid, guanidine-HCl, and EDTA, before SDS-electrophoresis followed by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). The electrophoretic patterns of the extracted proteins differed from that of COM and COD stones. LC-MS/MS identified 65 proteins, of which many were cellular plasma proteins, and were frequently detected regardless of the crystal components. However, 6 proteins (protein Z, protein S, prothrombin, osteopontin, fatty acid binding protein 5, and ubiquitin) were detected in the final EDTA fractions of COM stones. These proteins are involved in the coagulation process or osteometabolism, and thus the roles they play are of particular interest. PMID- 26353962 TI - Development and Validation of a New HPLC Method for the Simultaneous Determination of Paracetamol, Ascorbic Acid, and Pseudoephedrine HCl in their Co formulated Tablets. Application to in vitro Dissolution Testing. AB - The first HPLC method was developed for the simultaneous determination of paracetamol (PC), ascorbic acid (AA), and pseudoephedrine HCl (PE) in their co formulated tablets. Separation was achieved on a C18 column in 5 min using a mobile phase composed of methanol-0.05 M phosphate buffer (35:65, v/v) at pH 2.5 with UV detection at 220 nm. Linear calibration curves were constructed over concentration ranges of 1.0 - 50.0, 3.0 - 60.0 and 3.0 - 80.0 MUg mL(-1) for PC, AA, and PE, respectively. The method was validated and applied for the simultaneous determination of these drugs in their tablets with average % recoveries of 101.17 +/- 0.67, 98.34 +/- 0.77, and 98.95 +/- 1.11%, for PC, AA, and PE, respectively. The proposed method was also used to construct in vitro dissolution profiles of the co-formulated tablets containing the three drugs. PMID- 26353965 TI - Suppression of type I and type III IFN signalling by NSs protein of severe fever with thrombocytopenia syndrome virus through inhibition of STAT1 phosphorylation and activation. AB - Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick borne pathogen causing significant morbidity and mortality in Asia. NSs protein of SFTSV is known to perturb type I IFN induction and signalling, but the mechanism remains to be fully understood. Here, we showed the suppression of both type I and type III IFN signalling by SFTSV NSs protein is mediated through inhibition of STAT1 phosphorylation and activation. Infection with live SFTSV or expression of NSs potently suppressed IFN-stimulated genes but not NFkB activation. NSs was capable of counteracting the activity of IFN-alpha1, IFN beta, IFN-lambda1 and IFN-lambda2. Mechanistically, NSs associated with STAT1 and STAT2, mitigated IFN-beta-induced phosphorylation of STAT1 at S727, and reduced the expression and activity of STAT1 protein in IFN-beta-treated cells, resulting in the inhibition of STAT1 and STAT2 recruitment to IFNstimulated promoters. Taken together, SFTSV NSs protein is an IFN antagonist that suppresses phosphorylation and activation of STAT1. PMID- 26353964 TI - Decreased risk of acute myocardial infarction in stroke patients receiving acupuncture treatment: a nationwide matched retrospective cohort study. AB - BACKGROUND: Whether acupuncture protects stroke patients from acute myocardial infarction (AMI) has not been studied previously. The purpose of this study was to investigate the risk of AMI among stroke patients receiving acupuncture treatment. METHODS: Taiwan's National Health Insurance Research Database was used to conduct a retrospective cohort study of 23475 stroke patients aged 40-79 years receiving acupuncture treatment and 46950 propensity score-matched stroke patients not receiving acupuncture treatment who served as controls from 2000 to 2004. Both stroke cohorts were followed until the end of 2009 and were adjusted for immortal time to measure the incidence and adjusted hazard ratios (HRs) with 95 % confidence intervals (CIs) for new-onset AMI in multivariate Cox proportional hazard models. RESULTS: Stroke patients who received acupuncture treatment (9.2 per 1000 person-years) exhibited a lower incidence of AMI compared with those who did not receive acupuncture treatment (10.8 per 1000 person years), with an HR of 0.86 (95 % CI, 0.80-0.93) after adjusting for age, sex, low income, coexisting medical conditions and medications. The relationship between acupuncture treatment and AMI risk was investigated in female stroke patients (HR, 0.85; 95 % CI, 0.76-0.95), male stroke patients (HR, 0.87; 95 % CI, 0.80 0.95), patients from 50 to 59 years of age (HR, 0.75; 95 % CI, 0.63-0.90), patients from 60 to 69 years of age (HR, 0.85; 95 % CI, 0.75-0.95), patients suffering from ischemic stroke (HR, 0.87; 95 % CI, 0.79-0.95), and patients suffering from hemorrhagic stroke (HR, 0.62; 95 % CI, 0.44-0.88). CONCLUSIONS: We raised the possibility that acupuncture may be effective in lowering the risk of AMI in stroke patients aged 50-69 in this study, which was limited by a lack of information regarding stroke severity and acupuncture points. Our results suggest that prospective randomized trials are needed to establish the efficacy of acupuncture in preventing AMI. PMID- 26353966 TI - The novel approach to the biomonitor survey using one- and two-dimensional Kohonen networks. AB - To compare the applicability of the leaves of horse chestnut (Aesculus hippocastanum) and linden (Tilia spp.) as biomonitors of trace element concentrations, a coupled approach of one- and two-dimensional Kohonen networks was applied for the first time. The self-organizing networks (SONs) and the self organizing maps (SOMs) were applied on the database obtained for the element accumulation (Cr, Fe, Ni, Cu, Zn, Pb, V, As, Cd) and the SOM for the Pb isotopes in the leaves for a multiyear period (2002-2006). A. hippocastanum seems to be a more appropriate biomonitor since it showed more consistent results in the analysis of trace elements and Pb isotopes. The SOM proved to be a suitable and sensitive tool for assessing differences in trace element concentrations and for the Pb isotopic composition in leaves of different species. In addition, the SON provided more clear data on seasonal and temporal accumulation of trace elements in the leaves and could be recommended complementary to the SOM analysis of trace elements in biomonitoring studies. PMID- 26353967 TI - Evaluation of storage and evaporation in the removal efficiency of D-norgestrel and progesterone in human urine. AB - Pharmaceuticals are emerging contaminants and it must be noted that approximately 70 % of them are excreted via urine. Therefore, urine usage implies the risk of transfer of pharmaceutical residues to agricultural fields and environment contamination. Thus, this study aimed on the development and validation of a LC MS/MS method for D-norgestrel (D-NOR) and progesterone (PRO) determination in human urine, as well as the evaluation of the removal efficiency of two methods (storage and evaporation), and the effects of acidification with sulfuric acid. The storage process was evaluated for 6 weeks, while the evaporation was assessed at three different temperatures (50, 75, and 100 degrees C). All experiments were done with normal urine (pH = 6.0) and acidified urine (pH = 2.0, with sulfuric acid). The results of validation showed good method efficiency. In the second week of storage, higher hormone degradation was observed. In the evaporation method, both D-NOR and PRO were almost completely degraded when the volume was reduced to the lowermost level. Results also indicate that acidification did not affect degradation. Overall, the results showed that combination of two methods can be employed for more efficient hormone removal in urine. PMID- 26353968 TI - Effect of organic carbon chemistry on sorption of atrazine and metsulfuron-methyl as determined by (13)C-NMR and IR spectroscopy. AB - Soil organic matter (SOM) content is the major soil component affecting pesticide sorption. However, recent studies have highlighted the fact that it is not the total carbon content of the organic matter, but its chemical structure which have a profound effect on the pesticide's sorption. In the present study, sorption of atrazine and metsulfuron-methyl herbicides was studied in four SOM fractions viz. commercial humic acid, commercial lignin, as well as humic acid and humin extracted from a compost. Sorption data was fitted to the Freundlich adsorption equation. In general, the Freundlich slope (1/n) values for both the herbicides were <1. Except for atrazine sorption on commercial humic acid, metsulfuron methyl was more sorbed. Desorption results suggested that atrazine was more desorbed than metsulfuron-methyl. Lignin, which showed least sorption of both the herbicides, showed minimum desorption. Sorption of atrazine was best positively correlated with the alkyl carbon (adjusted R (2) = 0.748) and carbonyl carbon (adjusted R (2) = 0.498) but, their effect was statistically nonsignificant (P = 0.05). Metsulfuron-methyl sorption showed best positive correlation with carbonyl carbon (adjusted R (2) = 0.960; P = 0.05) content. Sorption of both the herbicides showed negative correlation with O/N-alkyl carbon. Correlation of herbicide's sorption with alkyl and carbonyl carbon content of SOM fractions suggested their contribution towards herbicide sorption. But, sorption of metsulfuron-methyl, relatively more polar than atrazine, was mainly governed by the polar groups in SOM. IR spectra showed that H-bonds and charge-transfer bonds between SOM fraction and herbicides probably operated as mechanisms of adsorption. PMID- 26353969 TI - Disproportionate effect on child admissions of the change in Medicines and Healthcare Products Regulatory Agency guidance for management of paracetamol poisoning: an analysis of hospital admissions for paracetamol overdose in England and Scotland. AB - OBJECTIVE: The aim of the present study was to assess the effects of the changes in the management of paracetamol overdose recommended by the UK Commission for Human Medicines on rates of hospital admission. METHODS: An interrupted time series analysis was carried out on data for hospital admissions for paracetamol poisoning for England between January 2010 and June 2014, and for Scotland between January 2010 and Sept. 2014. The main outcome measure was admissions to hospital with paracetamol poisoning (T39.1), as defined by first position coding in children and adults. RESULTS: The time series analysis (Jan 2010 to June 2014) showed that admission rates for paracetamol poisoning were steady from 2010 to the date of change (September 2012), with an estimated 269 [95% confidence interval (CI) 252.5, 285.5] child (0-14 years) and 3541 (95% CI 3454, 3628) adult admissions per month. In September 2013, 12 months after the change, there were an estimated additional 116 [37.3% (95% CI 17.2-67.4)] child and 426 [12.5% (95% CI 4.5-19.6)] adult admissions. Thus, in the year before the change (September 2011 to August 2012) there were 45,181 (3500 child and 41,681 adult) admissions, and in the year after (September 2012 to August 2013) there were 50,198 (4779 child and 45,419 adult) admissions. The overall proportion of child admissions was significantly greater after the change (Chi-square 32.486, P < 0.001), emphasizing the disproportionate effect in children. CONCLUSIONS: Changes to the management guidelines for paracetamol poisoning in September 2012 were rapidly implemented but have particularly increased paediatric hospital admissions for paracetamol poisoning. This impact in children, who are at low risk of mortality from paracetamol toxicity, appears excessive. PMID- 26353970 TI - 3D TiO2@Ni(OH)2 Core-shell Arrays with Tunable Nanostructure for Hybrid Supercapacitor Application. AB - Three dimensional hierarchical nanostructures have attracted great attention for electrochemical energy storage applications. In this work, self-supported TiO2@Ni(OH)2 core-shell nanowire arrays are prepared on carbon fiber paper via the combination of hydrothermal synthesis and chemical bath deposition. In this core-shell hybrid, the morphology and wall size of the interconnected nanoflake shell of Ni(OH)2 can be tuned through adjusting the concentration of ammonia solution. Heterogeneous nucleation and subsequent oriented crystal growth are identified to be the synthesis mechanism affecting the nanostructure of the shell material, which consequently determines the electrochemical performance in both energy storage and charge transfer. Superior capabilities of 264 mAh g(-1) at 1 A g(-1) and 178 mAh g(-1) at 10 A g(-1) are achieved with the core-shell hybrids of the optimized structure. The asymmetric supercapacitor prototype, comprising of TiO2@Ni(OH)2 as the anode and mesoporous carbons (MCs) as the cathode, is shown to exhibit superior electrochemical performance with high energy and power densities. The present work provides a clear illustration of the structure property relationship in nanocrystal synthesis and offers a potential strategy to enhance the battery type Ni(OH)2 electrode in a hybrid supercapacitor device. PMID- 26353971 TI - Bioinspired, roughness-induced, water and oil super-philic and super-phobic coatings prepared by adaptable layer-by-layer technique. AB - Coatings with specific surface wetting properties are of interest for anti fouling, anti-fogging, anti-icing, self-cleaning, anti-smudge, and oil-water separation applications. Many previous bioinspired surfaces are of limited use due to a lack of mechanical durability. Here, a layer-by-layer technique is utilized to create coatings with four combinations of water and oil repellency and affinity. An adapted layer-by-layer approach is tailored to yield specific surface properties, resulting in a durable, functional coating. This technique provides necessary flexibility to improve substrate adhesion combined with desirable surface chemistry. Polyelectrolyte binder, SiO2 nanoparticles, and silane or fluorosurfactant layers are deposited, combining surface roughness and necessary chemistry to result in four different coatings: superhydrophilic/superoleophilic, superhydrophobic/superoleophilic, superhydrophobic/superoleophobic, and superhydrophilic/superoleophobic. The superoleophobic coatings display hexadecane contact angles >150 degrees with tilt angles <5 degrees , whilst the superhydrophobic coatings display water contact angles >160 degrees with tilt angles <2 degrees . One coating combines both oleophobic and hydrophobic properties, whilst others mix and match oil and water repellency and affinity. Coating durability was examined through the use of micro/macrowear experiments. These coatings display transparency acceptable for some applications. Fabrication via this novel combination of techniques results in durable, functional coatings displaying improved performance compared to existing work where either durability or functionality is compromised. PMID- 26353972 TI - Gold/Palladium Alloy for Carbon-Halogen Bond Activation: An Unprecedented Halide Dependence. AB - New catalytic activity of gold/palladium alloy nanoclusters (NCs) for carbon halogen bond activation is demonstrated. In the case of an aryl chloride, the inclusion of gold in a bimetallic catalyst is indispensable to achieve the coupling reactions. Gold has the unique effect of stabilizing palladium, such that Pd(2+) leached from clusters by means of spillover of chloride during oxidative addition. The thus-formed spillover intermediate further reacts heterogeneously in both Ullmann and Suzuki-type coupling reactions through a new type of mechanism. In the case of an aryl bromide, Ullmann coupling occurs through the spillover of bromide, similar to that of aryl chloride. However, a significant fraction of palladium also leached, which diminished the Ullmann coupling activity of the aryl bromide and, as a result, the order of reactivity was ArCl>ArBr. With regard to the activation of the C-Br bond towards a Suzuki type reaction, the inclusion of a higher gold content in gold/palladium clusters stabilized palladium to prevent the leaching of Pd(2+) from the clusters by means of spillover of bromide. The spillover intermediate reacts heterogeneously with PhB(OH)2, palladium-rich gold/palladium, or pure palladium clusters; the oxidative addition of ArBr favors the extraction of palladium from the clusters, yielding Pd(2+) intermediates. The extracted intermediates react homogenously (Pd(2+/)Pd(0) catalysis) with PhB(OH)2, which results in the higher selectivity of the cross-coupling product. An initial step to observe such unprecedented halide dependency, together with the dynamic behavior of palladium on the surface of gold is the oxidative addition of Ar-X. A detailed insight into the first oxidative addition process was also examined by quantum chemical calculations. PMID- 26353973 TI - Young adults using e-cigarettes are more likely to progress to smoking, study shows. PMID- 26353974 TI - Influence of temperature on biomass production of clones of Atriplex halimus. AB - A very effective tool to combat desertification is revegetation. Promising species for this purpose are the evergreen shrubs of the genus Atriplex. The objective of the research was to study the growing responses of Atriplex halimus under different thermal regimes and to evaluate the biomass accumulation of selected clones. The test was carried out in four sites of Sardinia Island (Italy) characterized by different latitude, altitude and air temperature trends along the year. In every site, potted plants of five clones of A. halimus were compared for biomass production as measured by linear growth of plants (central axis and secondary shoots), as well as by dry weight of leaves, shoots and roots per plant. Correlations between sums of hour-degrees under or above the thresholds of critical air temperatures, comprised between 0 and 35 degrees C, and the plant growth indicators were analysed. Differences among the five clones, with regard to the influence of low temperatures on plant growth and on the biomass production were evaluated. Among five tested clones, GIO1 and SAN3 resulted more sensitive to low temperatures. Clones MAR1, PAL1 and FAN3 resulted less sensitive to low temperatures and in the site characterized by the lowest minimum temperatures also have shown greater adaptability and thus biomass growth in the observed period. The clone PAL1 showed a lower shoot/root biomass ratio as adaptation to cold temperature, and the clone FAN3, the opposite behaviour and a general preference to temperate thermal regimes. PMID- 26353975 TI - The Far Side of Vascular Injury: Nonconventional Vasoconstrictors, DNA-targeting Agents, and Agents Toxic to Vascular Smooth Muscle. AB - Substances historically thought to cause direct vascular injury in laboratory animals are a heterogeneous group of toxic agents with varied mechanisms of action. Morphologically, the reviewed agents can be broadly categorized into those targeting endothelial cell (ECs) and those targeting smooth muscle cells (SMCs). Anticancer drugs, immunosuppressants, and heavy metals are targeting primarily ECs while allylamine, beta-aminopropionitrile, and mitogen-activated protein kinase kinase inhibitors affect mainly SMCs. It is now recognized that the pathogenicity of some of these agents is often mediated through intermediary events, particularly vasoconstriction. There are clear similarities in the clinical and microscopic findings associated with many of these agents in animals and man, allowing the use of animal models to investigate mechanisms and pathogenesis. The molecular pathogenic mechanisms and comparative morphology in animals and humans will be reviewed. PMID- 26353977 TI - Alveolar Macrophage Distribution in a Mouse Model: The Importance of the Fixation Method. AB - Rodent lungs are routinely examined after intratracheal instillation (IT) of fixative. This study compares the histopathologic appearance of the lung after IT fixation with air inflation (AI) followed by immersion fixation. Lungs from mice chronically exposed to cigarette smoke were fixed either by IT or by AI. Increased numbers of macrophages with differing distributions were seen in both groups. Lungs fixed by IT had prominent, large macrophages floating in the alveolar lumina, as well as macrophage clusters and loose aggregates, often near terminal airways. Macrophages in lungs fixed by AI were randomly distributed throughout the lung, lying singly along alveolar walls, with large numbers visible in the interstitium. Clusters of macrophages were seen in the airways after AI but were fewer after IT fixation. The effects of intratracheal fixation on lung macrophages need to be considered carefully when assessing the significance of changes in macrophage appearance and distribution. PMID- 26353976 TI - Uterine Carcinomas in Tetrabromobisphenol A-exposed Wistar Han Rats Harbor Increased Tp53 Mutations and Mimic High-grade Type I Endometrial Carcinomas in Women. AB - Endometrial carcinoma is the most common gynecologic malignancy is the United States and accounts for 6% of all cancers in women. The disease is classified as type I or type II based on clinicopathologic and molecular features. It is a multifactorial disease with a number of risk factors, including environmental exposures. How environmental exposures, such as flame retardants, may affect the incidence of endometrial cancer is a topic of current and ongoing interest. Tetrabromobisphenol A (TBBPA) is a widely used brominated flame retardant found in a variety of household products. A recent 2-year National Toxicology Program carcinogenicity study found that exposure to TBBPA was associated with a marked increase in the development of uterine tumors, specifically uterine carcinomas, in Wistar Han rats. Molecularly, TBBPA-induced uterine carcinomas in Wistar Han rats were characterized by a marked increase in tumor protein 53 mutation compared to spontaneous uterine carcinomas, as well as overexpression of human epidermal growth factor receptor 2. Similar to spontaneous carcinomas, tumors in TBBPA-exposed rats were estrogen receptor-alpha positive and progesterone receptor negative by immunohistochemistry. The morphologic and molecular features of uterine carcinomas in TBBPA-exposed rats resemble those of high-grade type I tumors in women, and these data suggest that exposure to TBBPA may pose an increased cancer risk. PMID- 26353978 TI - Temporal Patterns of Novel Circulating Biomarkers in IL-2-mediated Vascular Injury in the Rat. AB - Recombinant interleukin-2 (rIL-2) administration in oncology indications is hampered by vascular toxicity, which presents as a vascular leak syndrome. We used this aspect of the toxicity of rIL-2 to evaluate candidate biomarkers of drug-induced vascular injury (DIVI) in rats given 0.36 mg/kg rIL-2 daily. Groups of rats were given either 2 or 5 doses of rIL-2 or 5 doses of rIL-2 followed by a 7-day recovery. The histomorphologic lexicon and grading scheme developed by the Vascular Injury Working Group of the Predictive Safety Testing Consortium of the Critical Path Institute were utilized to enable semiquantitative integration with circulating biomarker levels. The administration of rIL-2 was associated with time-dependent endothelial cell hyperplasia and hypertrophy and perivascular inflammation that correlated with increases in circulating angiopoietin-2, lipocalin-2, monocyte chemotactic protein-1, tissue inhibitor of metalloproteinase-1, vascular endothelial growth factor A, E-selectin, and chemokine (C-X-C motif) ligand-1, and the microRNAs miR-21, miR-132, and miR-155. The dose groups were differentially identified by panels comprising novel candidate biomarkers and traditional hematologic parameters. These results identify biomarkers of the early stages of DIVI prior to the onset of vascular smooth muscle necrosis. PMID- 26353979 TI - Is ambulatory arterial stiffness index a marker of large-artery stiffness? Evidence from intervention studies. PMID- 26353980 TI - Antecolic versus retrocolic duodenoenteric reconstruction after pancreatoduodenectomy. PMID- 26353982 TI - Effect of Polyelectrolyte and Fatty Acid Soap on the Formation of CaCO3 in the Bulk and the Deposit on Hard Surfaces. AB - The effects of sodium polyacrylate (NaPAA) as well as potassium oleate on the nucleation and calcium carbonate crystal growth on hard surfaces, i.e., stainless steel and silica, have been investigated at different temperatures. The relation between the surface deposition and the corresponding bulk processes has been revealed by combining dynamic light scattering (DLS), scanning electron microscopy (SEM), X-ray diffraction (XRD), and ellipsometry. The aim was to further our understanding of the crystal deposition/growth mechanism and how it can be controlled by the presence of polyelectrolytes (NaPAA) or soap (potassium oleate). The addition of polyelectrolytes (NaPAA) or soap (potassium oleate) decreases the size of CaCO3 particles in bulk solution and affects both crystal structure and morphology in the bulk as well as on hard surfaces. The amount of particles on hard surfaces decreases significantly in the presence of both potassium oleate and NaPAA. This was found to be a consequence of potassium oleate or NaPAA adsorption on the hard surface as well as on the CaCO3 crystal surfaces. Here, the polymer NaPAA exhibited a stronger inhibition effect on the formation and growth of CaCO3 particles than potassium oleate. PMID- 26353981 TI - Direct label-free measurement of the distribution of small molecular weight compound inside thick biological tissue using coherent Raman microspectroscopy. AB - Distributions of small molecular weight (less than 300 Da) compounds inside biological tissue have been obscure because of the lack of appropriate methods to measure them. Although fluorescence techniques are widely used to characterise the localisation of large biomolecules, they cannot be easily applied to the cases with small molecule compounds. We used CARS spectroscopy to detect and identify a label-free small molecule compound. To facilitate detection in aqueous environment, we utilised time-resolved and phase-sensitive techniques to reduce non-resonant background generated from water. We applied this technique to detect small molecular weight compound, taurine, inside mouse cornea tissue immersed in taurine solution as an initial model experiment. We detected a Raman peak of taurine near wavenumber 1033 cm(-1) inside cornea and successfully characterised its depth profile in the tissue. Our CARS spectra measurement can be a promising method to measure and visualise the distribution of small bio-related compounds in biological background without using any labeling, paving the way for new cell biological analysis in various disciplines. PMID- 26353983 TI - IOIBD technical review on endoscopic indices for Crohn's disease clinical trials. AB - BACKGROUND: Crohn's disease (CD) is a chronic disabling and progressive IBD. Only strategies looking beyond symptoms and based on tight monitoring of objective signs of inflammation such as mucosal lesions may have the potential for disease modification. Endoscopic evaluation is currently the gold standard to assess mucosal lesions and has become a major therapeutic endpoint in clinical trials. Several endoscopic indices have been proposed to evaluate disease activity; unvalidated and arbitrary definitions have been used in clinical trials for defining endoscopic response and endoscopic remission in CD. METHODS: In these recommendations from the International Organization for the Study of Inflammatory Bowel Disease, we first reviewed all technical aspects of available endoscopic scoring systems in the literature. Second, in order to achieve consensus on endoscopic definitions of remission and response in trials, a two-round vote based on a Delphi method was performed among 14 specialists in the field of IBDs. RESULTS: At the end of the voting process, the investigators ranked first a >50% decrease in Simple Endoscopic Score for Crohn's Disease (SES-CD) or Crohn's Disease Endoscopic Index of Severity for the definition of endoscopic response, and an SES-CD 0-2 for the definition of endoscopic remission in CD. All experts agreed on a Rutgeerts' score i0-i1 for the definition of endoscopic remission after surgery. PMID- 26353984 TI - The Role of Physical Therapists Within Hospice and Palliative Care in the United States and Canada. AB - PURPOSE: Little is known regarding the extent to which physical therapy is integrated into Hospice and Palliative Care (HPC). The purpose of this study was to describe perceptions of physical therapists (PTs) regarding their role within HPC or working with patients having life-threatening illnesses and to develop a conceptual framework depicting a PTs role within HPC and factors affecting it. PARTICIPANTS: Ten PTs, 5 from the United States and 5 from Canada, with at least 5 years of physical therapy experience and 5 years working experience with patients having life-threatening illnesses or in HPC. METHODS: Demographic data were collected by electronic questionnaire. A semistructured interview was conducted with each participant to investigate their perceptions about the role of PTs in HPC. DATA ANALYSIS: Interview results were analyzed for trends between participants, practice settings, regions, and other sociocultural aspects. The constant comparative method of qualitative data analysis was used to identify similarities and differences and to develop themes and concepts relative to the role of PT in HPC. RESULTS: Participants identified their 3 primary roles in HPC: providing patient/family care, serving as an interdisciplinary team member, and fulfilling professional responsibilities outside of direct patient care. They described factors within and outside direct patient care which influenced their roles. Concepts included shifting priorities, care across the continuum, and changing perceptions of PTs within HPC. CLINICAL RELEVANCE: This study described perceptions of the role of PTs within HPC that may be utilized when coordinating future strategies to appropriately promote and expand the role. PMID- 26353985 TI - Conclusiveness of the Cochrane Reviews in Palliative and Supportive Care for Cancer. AB - To assess the conclusiveness of the Cochrane reviews (CRs) in the field of palliative and supportive care for cancer. We searched the CRs on Pain, Palliative, and Supportive Care Group available in the Cochrane library on February 01, 2015, to analyze whether a CR could reach a clinical decision. Each CR was analyzed for conclusiveness, number of randomized controlled trials (RCTs) enrolled, number of participants enrolled, the need for further studies, and the reasons. Only 45% (30 of 66) of the CRs reached definitive clinical recommendations. The number of RCTs and participants enrolled in conclusive CRs were significantly higher than those in inconclusive CRs. Nearly all CRs recognized the need for further studies. The conclusiveness was not affected by the year of publication. We concluded that a large number of clinical trials were not carried out well in the palliative and supportive oncology. PMID- 26353987 TI - Effect of structural parameters on the electron capture dissociation and collision-induced dissociation pathways of copper(II)-peptide complexes. AB - The gas-phase dissociation pathways of proteins/peptides are usually affected by the nature of the charge carrier and the sequence of amino acid residues. The effects of peptide structural parameters, including peptide composition, chain length and amide hydrogen, on the gas-phase dissociation of Cu(II)-model peptide complexes were explored in this study. Polyglycine peptides with flexible frames were used as probes to reduce the complexity of the system and illustrate the mechanism. Results revealed that the types of fragment ions generated in the electron capture dissociation (ECD) of Cu(II)-adducted peptides changed according to the basic amino acid residue composition. Charged or neutral tryptophan side chain losses were observed in the collision-induced dissociation (CID) of Cu(II) peptide complexes. Internal electron transfer between tryptophan and metal ion within the complex occurred during the CID reaction, leaving the charge-reduced Cu(+) as a closed d-shell stable electron configuration. The choice of the reaction channel was then determined by the gas-phase basicity of the peptide. Amide hydrogen was critical in the formation of metalated b-/y-ions in the ECD process as determined through mutation of the backbone amide group. Increasing the chain length suppressed the ECD of Cu-metalated peptide species. Our results indicate that the structural parameters of peptides play important roles in the gas-phase dissociation processes of Cu-peptide complexes. PMID- 26353986 TI - Suicidal behavior and spiritual functioning in a sample of Veterans diagnosed with PTSD. AB - BACKGROUND: Spiritual well-being has been lauded to exert a protective effect against suicidal behavior. This study examines the characteristics of spiritual functioning and their association with a self-reported history of suicidal thoughts and behavior in a sample of Veterans being treated for post-traumatic stress disorder (PTSD). METHODS: The sample includes 472 Veterans admitted to a PTSD Residential Rehabilitation Program. Measures included the Brief Multidimensional Measure of Religiousness and Spirituality, PTSD Checklist- Military Version, Combat Experiences Scale, and individual items pertaining to history of suicidal thoughts and attempts, spiritual practices, and select demographics. RESULTS: Problems with forgiveness and negative religious coping were uniquely associated with suicide risk, above and beyond age, gender, or ethnicity, combat exposure, and severity of PTSD symptomatology. Organizational religiousness was associated with decreased risk for thinking about suicide in the presence of these covariates. Daily spiritual experiences were inversely associated with suicidal thoughts. Differences in spirituality factors did not distinguish Veterans with both suicidal ideation and prior attempts from those who had ideations absent any prior attempts. CONCLUSIONS: The findings suggest that enhanced or diminished spiritual functioning is associated with suicidal thoughts and attempts among Veterans dealing with PTSD. PMID- 26353988 TI - Zwitterionic sulfonates as m/z shift reagents for 5-methylcytosine detection in deoxyribonucleic acids (DNA) using flow injection analysis and electrospray ionization mass spectrometry. AB - 5-Methylcytosine (5-MC) is an important epigenetic modification of DNA. Abnormally high concentrations of this substance appear because of the hypermethylation of cytosine. Therefore, the measurement of the quantity of this compound in mammals is of great importance. Recently, we reported that several imidazolium-based zwitterionic sulfonates form complexes with 5-MC in solution, which can be studied by electrospray ionisation mass spectrometry (ESI-MS). It is shown in this paper that such an association can be utilised for the detection of 5-MC in a DNA sample using high-throughput a flow injection analysis ESI-MS method. A variety of the sulfonate zwitterions have been tested as m/z shift reagents to increase the selectivity of the analysis. It is shown that either of the zwitterions can be used without the loss of sensitivity. The performance of the method was tested in terms of linearity range, sensitivity, intra- and between-day precision and accuracy, matrix effect and carryover. The method described is characterised by simplicity, a good limit of quantitation (1 pg injected) and low run times (at least 50 injections per hour). In addition, high performance liquid chromatography and tandem mass spectrometry are not required. The possibility exists to widen the scope of the method to other amidine containing compounds present in more complicated matrices. PMID- 26353989 TI - Evaluation of intermolecular association of glycosaminoglycan oligosaccharides using nanoelectrospray ionization mass spectrometry. AB - This study examines the non-covalent interactions between glycosaminoglycan (GAG) oligosaccharides using nanoelectrospray ionization mass spectrometry (nanoESI MS). It is the first time that interactions between oligosaccharides have been observed using MS. The importance of interactions between GAGs has recently attracted much interest because they are related to biological functions. For instance, hyaluronic acid (HA) is known to associate with chondroitin sulfates (CSs), although the details of the interaction remain unclear. In general, non covalent interactions between glycans are too weak to detect by general means. In this work, we applied nanoESI-MS with high sensitivity, which is widely used to observe non-covalent interactions, to investigate the interaction between HA and CSs. HA and CS oligosaccharides are used to discuss the results in a simplified manner. Our approach is aimed at interpreting the behavior of GAG polysaccharides from the information obtained using the oligosaccharides. HA and CS tetrasaccharides were demonstrated to associate to form heterodimer ions that were easily detected using nanoESI-MS. We also determined the stoichiometry of the interaction and calculated the K(d) values of the interactions between HA and CS tetrasaccharides. How these structures affect the strength and stability of the non-covalent complexes is discussed. Further study of the interactions between HA and CS oligosaccharides will clarify the biological meaning of the coexistence of HA and CS in body fluids and tissues. PMID- 26353990 TI - Electrospray ionization linear trap quadrupole Orbitrap in analysis of old tempera paintings: application to nineteenth-century Orthodox icons. AB - Proteomic approach in combination with mass spectrometry demonstrates a great potential for identification of proteinaceous materials in works of art. In this study we used a linear trap quadrupole Orbitrap (LTQ-Orbitrap), a state-of-the art mass spectrometer for parts per million accuracy analyses of peptides behind tryptic hydrolysis. After the efficiency of the proteomic method was confirmed for reference and model samples, micro-samples from historical paintings were for the first time analysed using this technique. Superior performances of the liquid chromatography-mass spectrometry approach using a LTQ-Orbitrap mass spectrometer allowed identification of egg yolk peptides in two samples from nineteenth century Orthodox icons, indicating egg tempera as the painting technique. Accurate precursor ion masses, in the range of +/-2 ppm, and retention times of tryptic peptides strengthen protein identification. Additionally, in all historical samples the presence of animal glues suggested that the ground layer was likely bound using bovine collagen. Comparing to results acquired using matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry in our previous study, here we achieved higher ion scores and protein scores, better sequence coverage and more identified proteins. In fact, a combination of the two mass spectrometric techniques provided overlapping and complementary data, related to the detection of peptides with different physicochemical properties. PMID- 26353991 TI - Ancient pottery from archaeological sites in Southern Italy: first evidence of red grape products markers. AB - The chemical analysis of tartaric acid (TA) and syringic acid (SA), as grape product markers in ancient ceramic vessels from the sites of Manduria and Torre di Satriano (southern Italy), was successfully performed. Firstly, the fragmentation behaviour of TA and SA as deprotonated molecules, [M-H](-), obtained by collision-induced dissociation, was investigated. Then, reversed phase liquid chromatography (RPLC) with electrospray ionization (ESI) in negative ion mode, using a quadrupole linear ion trap in multiple reaction monitoring (MRM), was employed. A binary mobile phase composed of water-acetonitrile with 0.1% (v/v) acetic acid enabled the optimum ESI efficiency of SA, greatly improving its identification when it occurs in trace amounts. Chemical analysis of ancient pottery fragments is a valid method for establishing the existence of preserved organic residues, which is valuable new evidence for the culture and customs of ancient populations, in this case those of southern Italy. The proposed RPLC-ESI-MRM method allowed a systematic investigation of ceramic fragments of both archaeological sites, thus providing positive evidence for the presence of TA and SA as grape product markers in storage vessels dating back to the ninth to third centuries BC. PMID- 26353992 TI - Letter: beta-Cyclodextrin affects the formation of isomerization products during peptide deamidation. AB - Cyclodextrins (CDs) are a group of nontoxic oligosaccharides that are widely used as drug excipients and protein stabilizers. CDs have also been found to reduce the neurotoxicity and fibrillation of amyloid beta (Abeta), the major component of the amyloid plaques found in the brain of patients suffering from Alzheimer's disease. The formation of these plaques was found to be enhanced by the presence of iso-aspartic acid (isoAsp) residues in the Abeta peptide, which can be formed by deamidation from asparagine (Asn). To explore further the influence of CDs on Abeta, we investigated three Asn-containing peptides, including Abeta25-35, by electrospray ionization, electron capture dissociation, and Fourier-transform ion cyclotron resonance mass spectrometry to explore details of the deamidation process in the presence and absence of peptide/CD adducts. The results showed that CDs reduced the formation of the isomerization product isoAsp during peptide deamidation. This finding might help to better understand the role of CDs during the protein-aggregation process. PMID- 26353993 TI - Letter: Evaluation and comparison of collision-induced dissociation and electron capture dissociation for top-down analysis of intact ribonuclease B. AB - It has been previously reported that the glycosylation site and protein-sequence information could be obtained for ribonuclease B by top-down electron-capture dissociation (ECD) and collision-induced dissociation (CID) mass spectrometry (MS). However, the sequence coverage of ribonuclease B was limited in a single activation, and the structural information on the glycan moiety was not probed successfully in previous experiments. Here, we demonstrate that ECD and CID techniques can be used together as an effective top- down method for the structural characterization of intact glycoprotein. Even without an elaborate pre or post- ECD activation, a high sequence coverage (<90%) of ribonuclease B could be achieved with substantial amounts of structural information for the glycan moiety. By comparing our work with previous results, it is postulated that the disulfide bond reduction strategy might play a significant role in determining the efficiency of top-down MS. PMID- 26353994 TI - Transgranular liquation cracking of grains in the semi-solid state. AB - Grain refinement via semi-solid deformation is desired to obtain superior mechanical properties of cast components. Using quantitative in situ synchrotron X-ray tomographic microscopy, we show an additional mechanism for the reduction of grain size, via liquation assisted transgranular cracking of semi-solid globular microstructures. Here we perform localized indentation of Al-15wt.%Cu globular microstructures, with an average grain size of ~480 MUm, at 555 degrees C (74% solid fraction). Although transgranular fracture has been observed in brittle materials, our results show transgranular fracture can also occur in metallic alloys in semi-solid state. This transgranular liquation cracking (TLC) occurs at very low contact stresses (between 1.1 and 38 MPa). With increasing strain, TLC continues to refine the size of the microstructure until the grain distribution reaches log-normal packing. The results demonstrate that this refinement, previously attributed to fragmentation of secondary arms by melt shearing, is also controlled by an additional TLC mechanism. PMID- 26353995 TI - Robotic resection of a mediastinal parathyroid cyst. AB - Mediastinal parathyroid cysts (PC) are rare, benign lesions, reported in fewer than 150 cases worldwide. Although most are asymptomatic and discovered incidentally on imaging, symptoms of dyspnea, dysphagia, hoarseness, palpitations, hypercalcemia, and innominate or jugular venous thrombosis have been reported. Sternotomy or thoracotomy has traditionally been the approach used to resect mediastinal PCs. We describe the first reported case of a robot assisted resection of a mediastinal PC. PMID- 26353996 TI - Spectroscopic and Kinetic Evidence for the Crucial Role of Compound 0 in the P450cam -Catalyzed Hydroxylation of Camphor by Hydrogen Peroxide. AB - The hydroperoxo iron(III) intermediate P450cam Fe(III) -OOH, being the true Compound 0 (Cpd 0) involved in the natural catalytic cycle of P450cam , could be transiently observed in the peroxo-shunt oxidation of the substrate-free enzyme by hydrogen peroxide under mild basic conditions and low temperature. The prolonged lifetime of Cpd 0 enabled us to kinetically examine the formation and reactivity of P450cam Fe(III) -OOH species as a function of varying reaction conditions, such as pH, and concentration of H2 O2 , camphor, and potassium ions. The mechanism of hydrogen peroxide binding to the substrate-free form of P450cam differs completely from that observed for other heme proteins possessing the distal histidine as a general acid-base catalyst and is mainly governed by the ability of H2 O2 to undergo deprotonation at the hydroxo ligand coordinated to the iron(III) center under conditions of pH>=p${K{{{?rm P450}?hfill ?atop {?rm a}?hfill}}}$. Notably, no spectroscopic evidence for the formation of either Cpd I or Cpd II as products of heterolytic or homolytic O?O bond cleavage, respectively, in Cpd 0 could be observed under the selected reaction conditions. The kinetic data obtained from the reactivity studies involving (1R)-camphor, provide, for the first time, experimental evidence for the catalytic activity of the P450Fe(III) -OOH intermediate in the oxidation of the natural substrate of P450cam . PMID- 26353997 TI - Photoinduced Charge Transport in a BHJ Solar Cell Controlled by an External Electric Field. AB - This study investigated theoretical photoinduced charge transport in a bulk heterojunction (BHJ) solar cell controlled by an external electric field. Our method for visualizing charge difference density identified the excited state properties of photoinduced charge transfer, and the charge transfer excited states were distinguished from local excited states during electronic transitions. Furthermore, the calculated rates for the charge transfer revealed that the charge transfer was strongly influenced by the external electric field. The external electric field accelerated the rate of charge transfer by up to one order when charge recombination was significantly restrained. Our research demonstrated that photoinduced charge transport controlled by an external electric field in a BHJ solar cell is efficient, and the exciton dissociation is not the limiting factor in organic solar cells.Our research should aid in the rational design of a novel conjugated system of organic solar cells. PMID- 26353998 TI - Young Hispanic Women Experience Higher In-Hospital Mortality Following an Acute Myocardial Infarction. AB - BACKGROUND: Although mortality rates for acute myocardial infarction (AMI) have declined for men and women, prior studies have reported a sex gap in mortality such that younger women were most likely to die after an AMI. METHODS AND RESULTS: We sought to explore the impact of race and ethnicity on the sex gap in AMI patterns of care and mortality for younger women in a contemporary patient cohort. We constructed multivariable hierarchical logistic regression models to examine trends in AMI hospitalizations, procedures, and in-hospital mortality by sex, age (<65 and >=65 years), and race/ethnicity (white, black, and Hispanic). Analyses were derived from 194 071 patients who were hospitalized for an AMI with available race and ethnicity data from the 2009-2010 National Inpatient Sample. Hospitalization rates, procedures (coronary angiography, percutaneous coronary interventions, and cardiac bypass surgery), and inpatient mortality were analyzed across age, sex, and race/ethnic groups. There was significant variation in hospitalization rates by age and race/ethnicity. All racial/ethnic groups were less likely to undergo invasive procedures compared with white men (P<0.001). After adjustment for comorbidities, younger Hispanic women experienced higher in hospital mortality compared with younger white men, with an odds ratio of 1.5 (95% CI 1.2 to 1.9), adjusted for age and comorbidities. CONCLUSION: We found significant racial and sex disparities in AMI hospitalizations, care patterns, and mortality, with higher in-hospital mortality experienced by younger Hispanic women. Future studies are necessary to explore determinants of these significant racial and sex disparities in outcomes for AMI. PMID- 26353999 TI - Age and the amplitude of accommodation measured using dynamic retinoscopy. AB - PURPOSE: Dynamic retinoscopy (DR) is a procedure for assessing the accommodative response using a standard clinical instrument. The present study compared measurements of the amplitude of accommodation (AA) obtained using this technique with two subjective methods (modified push-down and minus lens). Additionally, the expected ranges for AA when measured by DR were determined. METHOD: AA was measured in 1298 subjects between 5 and 60 years of age using the three techniques described above. Subjects were grouped into 5-year bins, and a descriptive univariate analysis of the data performed. Goodness-of fit plots were constructed to examine the overall model fit. Centile curves were calculated from the final model. RESULTS: Mean values of AA obtained using DR were significantly lower than for the two subjective techniques. For the DR findings, no significant change was observed between 5 and 19 years of age (mean AA = 8.3 D) and between 45 and 60 years of age (mean AA = 0.6 D). AA values as a function of age were best fit by the polynomial regression equation: logAA = 1.93 + 0.49(age) - 0.19(age)(2) . CONCLUSION: Measurements of AA determined using DR are significantly lower than the normative subjective findings published previously. This difference is at least partly due to the depth-of-field of the eye. These norms markedly overestimate accommodative responsivity. DR provides a simple technique for quantifying accommodation in the clinical setting. PMID- 26354000 TI - Near full-length HIV type 1M genomic sequences from Cameroon : Evidence of early diverging under-sampled lineages in the country. AB - BACKGROUND: Cameroon is the country in which HIV-1 group M (HIV-1M) likely originated and is today a major hotspot of HIV-1M genetic diversity. It remains unclear, however, whether the highly divergent HIV-1M lineages found in this country arose during the earliest phases of the global HIV-1M epidemic, or whether they arose more recently as a result of recombination events between globally circulating HIV-1M lineages. METHODOLOGY: To differentiate between these two possibilities, we performed phylogenetic analyses of the near full genome sequences of nine newly sequenced divergent HIV-1M isolates and 15 previously identified, apparently unique recombinant forms (URFs) from Cameroon. RESULTS: Although two of the new genome sequences were clearly classifiable within subtype G, the remaining seven were highly divergent and phylogenetically branched either outside of, or very near the bases of clades containing the well characterised globally circulating viral lineages that they were most closely related to. Recombination analyses further revealed that these divergent viruses were likely complex URFs. We show, however that substantial portions (>1 Kb) of three of the new genome sequences and 15 of the previously characterised Cameroonian URFs have apparently been derived from divergent parental viruses that branch phylogenetically near the bases of the major HIV-1M clades. CONCLUSIONS AND IMPLICATIONS: Our analyses indicate the presence in Cameroon of contemporary descendants of numerous early-diverging HIV-1M lineages. Further efforts to sample and sequence viruses from such lineages could be crucial both for retracing the earliest evolutionary steps during the emergence of HIV-1M in humans, and accurately reconstructing the ancestral sequences of the major globally circulating HIV-1M lineages. PMID- 26354002 TI - Ultrafast isomerization initiated by X-ray core ionization. AB - Rapid proton migration is a key process in hydrocarbon photochemistry. Charge migration and subsequent proton motion can mitigate radiation damage when heavier atoms absorb X-rays. If rapid enough, this can improve the fidelity of diffract before-destroy measurements of biomolecular structure at X-ray-free electron lasers. Here we study X-ray-initiated isomerization of acetylene, a model for proton dynamics in hydrocarbons. Our time-resolved measurements capture the transient motion of protons following X-ray ionization of carbon K-shell electrons. We Coulomb-explode the molecule with a second precisely delayed X-ray pulse and then record all the fragment momenta. These snapshots at different delays are combined into a 'molecular movie' of the evolving molecule, which shows substantial proton redistribution within the first 12 fs. We conclude that significant proton motion occurs on a timescale comparable to the Auger relaxation that refills the K-shell vacancy. PMID- 26354003 TI - A systematic review on factors and consequences of parental distress as related to childhood cancer. AB - The literature including correlates of parental distress as related to childhood cancer is abundant. It is important to identify predictive factors and outcomes of this distress in parents. The objective of this review was to update previous syntheses on factors of distress and to identify outcomes of parents' distress in the recent literature (2007-2012). We performed a systematic review to identify all quantitative studies including measures of parental distress and associated factors during the study period. We found 56 eligible studies, of which 43 had a Low risk of bias (Cochrane guidelines). Forty-two reports included potential predictive factors. Significant relationships were found with clinical history of the child, sex of the parent, coping response and personal resources, pre diagnosis family functioning, but not education/income or marital status. Twenty five reports studied potential consequences of distress and focused on psychological adjustment in parents and children. Compared to past periods, a higher proportion of studies included fathers. Measures used to evaluate distress were also more homogeneous in certain domains of distress. This review underscores the need for appropriate methods for selecting participants and reporting results in future studies. Appropriate methods should be used to demonstrate causality between factors/consequences and distress. PMID- 26354005 TI - I will help you because we are similar: Quality of contact mediates the effect of perceived similarity on facilitative behaviour towards immigrants. AB - This research aimed to analyse interpersonal behaviour towards immigrants by exploring related psychosocial variables such as intergroup similarity and quality of intergroup contact. A new interpersonal behavioural tendencies scale was developed. In Study 1, Spanish participants reported their willingness to take different actions towards a Moroccan (i.e. a devalued target, n = 132) or an Ecuadorian (i.e. a valued target, n = 138), perceived intergroup similarity and quality of intergroup contact. Multigroup confirmatory factor analysis identified the expected dimensions: active facilitation (AF), passive facilitation (PF), passive harm (PH) and active harm (AH). Participants reported less similarity, less pleasant contact, less AF and less PF, and more PH with respect to Moroccans relative to Ecuadorians. Quality of contact mediated the effect of perceived similarity on interpersonal behaviour (especially facilitative behaviour) towards immigrants. Study 2 (N = 134) confirmed that this mediation effect also applied to Romanian immigrants, and tested a serial mediation pathway, in which perceived similarity affected symbolic threat, which in turn affected quality of contact, which finally affected behaviour. Changing perceived intergroup similarity might be a way of improving the quality of contact with minority groups, and this would be expected to increase pro-social behaviour towards such groups. PMID- 26354004 TI - Late progamic phase and fertilization affect calreticulin expression in the Hyacinthus orientalis female gametophyte. AB - KEY MESSAGE: Calreticulin expression is upregulated during sexual reproduction of Hyacinthus orientalis, and the protein is localized both in the cytoplasm and a highly specialized cell wall within the female gametophyte. Several evidences indicate calreticulin (CRT) as an important calcium (Ca(2+))-binding protein that is involved in the generative reproduction of higher plants, including both pre fertilization and post-fertilization events. Because CRT is able to bind and sequester exchangeable Ca(2+), it can serve as a mobile intracellular store of easily releasable Ca(2+) and control its local cytosolic concentrations in the embryo sac. This phenomenon seems to be essential during the late progamic phase, gamete fusion, and early embryogenesis. In this report, we demonstrate the differential expression of CRT within Hyacinthus female gametophyte cells before and during anthesis, during the late progamic phase when the pollen tube enters the embryo sac, and at the moment of fertilization and zygote/early endosperm activation. CRT mRNA and the protein localize mainly to the endoplasmic reticulum (ER) and Golgi compartments of the cells, which are involved in sexual reproduction events, such as those in sister synergids, the egg cell, the central cell, zygote and the developing endosperm. Additionally, immunogold research demonstrates selective CRT distribution in the filiform apparatus (FA), a highly specific component of the synergid cell wall. In the light of our previous data showing the total transcriptional activity of the Hyacinthus female gametophyte and the results presented here, we discuss the possible functions of CRT with respect to the critical role of Ca(2+) homeostasis during key events of sexual plant reproduction. Moreover, we propose that the elevated expression of CRT within the female gametophyte is a universal phenomenon in the cells involved in double fertilization in higher plants. PMID- 26354006 TI - Differentiation of stem cells derived from carious teeth into dopaminergic-like cells. AB - AIM: To investigate whether dental pulp stem cells from carious teeth (DPSCs-CT) can differentiate into functional dopaminergic-like (DAergic) cells and provide an alternative cell source in regenerative medicine. METHODOLOGY: Dental pulp stem cells from healthy (DPSCs) and carious teeth (DPSCs-CT) were isolated from young donors. Both cell lines were expanded in identical culture conditions and subsequently differentiated towards DAergic-like cells using pre-defined dopaminergic cocktails. The dopaminergic efficiencies were evaluated both at gene and protein as well as at secretome levels. RESULTS: The efficiency of DPSCs-CT to differentiate into DAergic-like cells was not equivalent to that of DPSCs. This was further reflected in both gene and protein generation whereby key neuronal markers such as nestin, NURR1 and beta-III-tubulin were expressed significantly lower as compared to differentiated DPSCs (P < 0.05). In addition, expressions of transcriptomes related to neurogenesis revealed downregulation of more than 50% of the genes as compared to differentiated DPSC (P < 0.05). Amongst the notable genes were those from the transcription factors family (FLNA, MEF2C, NEUROG2), signalling pathway family (DLL1, Notch1, TGF-beta1), neuro-inducer family (BDNF) and cell communication family (APBB1). CONCLUSIONS: DPSCs-CT were able to differentiate into DAergic-like cells but not as efficiently as DPSCs. As such, prior to use in regenerative medicine, stem cells from any source should be thoroughly investigated beyond conventional benchmarks such as that proposed by the International Society for Cellular Therapy (ISCT). PMID- 26354007 TI - Genetic variation and selfing rate in Lychnis flos-cuculi along an industrial pollution gradient. AB - We studied nine populations of a meadow mixed-mating plant Lychnis flos-cuculi growing in a gradient of copper smelter emissions. We hypothesize that metal tolerant populations in the polluted areas have experienced a loss of genetic variation and are more selfing than the populations from the unpolluted areas. One hundred and thirty-five parental plants and 1059 offspring were genotyped with six microsatellite markers. Selfing rates were assessed manually, with Rmes, Mltr and Colony2. Soil toxicity, population density and pollinators' activity were estimated in the studied areas. Populations from the heavily polluted area have experienced a strong founder effect. However, at present, they are characterized by high densities. A recent genetic explosion was registered for the population from the most polluted site, probably due to forest thinning under pollution effects. Selfing rates estimated with different approaches agreed well only for populations with high genetic variation; they comprised 0-0.23 and were similar between polluted and clean areas. Self-fertilization in L. flos-cuculi hardly represents a mechanism for the fixation of advantageous alleles and a barrier for gene flow from non-tolerant populations. The employment of different methods of selfing rate estimation in populations with low genetic variation appears to be necessary, though not a guarantee of reliable conclusions. PMID- 26354008 TI - Is pre-discharge echocardiography indicated for asymptomatic neonates with a heart murmur? A retrospective analysis. AB - OBJECTIVE: The purpose of this study was to determine whether a murmur detected on routine pre-discharge examination of asymptomatic newborn children in the first 48 hours of life warrants further investigation with echocardiography. METHODS: We conducted a retrospective review of all echocardiography studies of neonates born at Jordan University Hospital between August, 2007 and June, 2014. Findings on physical examination as well as the indication of the echocardiographic studies were reviewed. We included asymptomatic neonates for whom echocardiographic studies were carried out due to the sole indication of a heart murmur on routine pre-discharge neonatal physical examination. RESULTS: Of 309 asymptomatic newborns with murmurs on pre-discharge examination, echocardiography revealed 68 (22%) cases of CHD, with 18 (6%) designated as significant heart disease with anticipated intervention during infancy or childhood. The most common abnormality was ventricular septal defect occurring in 36 cases. Critical heart diseases detected included hypoplastic left heart syndrome in two and aortic valve stenosis in four newborns. CONCLUSIONS: Although most asymptomatic neonates with heart murmurs have normal hearts, a small percentage may have significant heart disease. The decision to refer an asymptomatic newborn with a murmur for echocardiography before discharge from the hospital remains controversial and must be supported by other evidence such as murmur characteristics and local trends in parental compliance with follow-up well-baby visits. PMID- 26354001 TI - Diametrical diseases reflect evolutionary-genetic tradeoffs: Evidence from psychiatry, neurology, rheumatology, oncology and immunology. AB - Tradeoffs centrally mediate the expression of human adaptations. We propose that tradeoffs also influence the prevalence and forms of human maladaptation manifest in disease. By this logic, increased risk for one set of diseases commonly engenders decreased risk for another, diametric, set of diseases. We describe evidence for such diametric sets of diseases from epidemiological, genetic and molecular studies in four clinical domains: (i) psychiatry (autism vs psychotic affective conditions), (ii) rheumatology (osteoarthritis vs osteoporosis), (iii) oncology and neurology (cancer vs neurodegenerative disorders) and (iv) immunology (autoimmunity vs infectious disease). Diametric disorders are important to recognize because genotypes or environmental factors that increase risk for one set of disorders protect from opposite disorders, thereby providing novel and direct insights into disease causes, prevention and therapy. Ascertaining the mechanisms that underlie disease-related tradeoffs should also indicate means of circumventing or alleviating them, and thus reducing the incidence and impacts of human disease in a more general way. PMID- 26354010 TI - [Kampo pharmacology: cardiovascular effects of a phytochemical, sinomenine, contained in Sinomenium acutum Rehder et Wilson]. PMID- 26354009 TI - Galactofuranose in Mycoplasma mycoides is important for membrane integrity and conceals adhesins but does not contribute to serum resistance. AB - Mycoplasma mycoides subsp. capri (Mmc) and subsp. mycoides (Mmm) are important ruminant pathogens worldwide causing diseases such as pleuropneumonia, mastitis and septicaemia. They express galactofuranose residues on their surface, but their role in pathogenesis has not yet been determined. The M. mycoides genomes contain up to several copies of the glf gene, which encodes an enzyme catalysing the last step in the synthesis of galactofuranose. We generated a deletion of the glf gene in a strain of Mmc using genome transplantation and tandem repeat endonuclease coupled cleavage (TREC) with yeast as an intermediary host for the genome editing. As expected, the resulting YCp1.1-Deltaglf strain did not produce the galactofuranose-containing glycans as shown by immunoblots and immuno electronmicroscopy employing a galactofuranose specific monoclonal antibody. The mutant lacking galactofuranose exhibited a decreased growth rate and a significantly enhanced adhesion to small ruminant cells. The mutant was also 'leaking' as revealed by a beta-galactosidase-based assay employing a membrane impermeable substrate. These findings indicate that galactofuranose-containing polysaccharides conceal adhesins and are important for membrane integrity. Unexpectedly, the mutant strain showed increased serum resistance. PMID- 26354011 TI - [Sesquiterpenoids: phytochemicals for the fight against cancers]. PMID- 26354012 TI - [Effects of evodiamine, a major alkaloid of Goshuyu (Evodia Fruits), on TRPV1]. PMID- 26354013 TI - [The vascular pharmacological effects induced by quercetin contained in Kampo herbal medicine]. PMID- 26354014 TI - [Amyloid and tau imaging, its present and future]. PMID- 26354015 TI - [Pharmacological and clinical profile of a new SGLT2 inhibitor, luseogliflozin (Lusefi(r))]. PMID- 26354016 TI - [Preclinical and clinical properties of vaniprevir (VANIHEP(r) Capsules 150 mg), a novel therapeutic agent for hepatitis C]. PMID- 26354017 TI - [Developmental neurotoxicity and stem cells]. PMID- 26354018 TI - [Characteristics of tumor endothelial cells]. PMID- 26354019 TI - Mining of novel species-specific primers for PCR detection of Listeria monocytogenes based on genomic approach. AB - Listeria monocytogenes in contaminated food is considered as a serious health threat for consumers due to its high mortality rate. The objective of this study was to obtain novel species-specific target-genes and primers for the molecular detection of L. monocytogenes using a comparative genomic approach. By comparative analysis of L. monocytogenes and non-L. monocytogenes genome sequences in the GenBank database with BLAST program, 26 specific target sequences were used as candidates and the primers were designed for L. monocytogenes species-specificity verification by using PCR assay. Finally, the three genes LMOf2365_0970, LMOf2365_2721 and mpl were identified to have L. monocytogenes species-specificity and be unique as detection targets for diagnostic application. The species-specific primer Lm8 of gene LMOf2365_0970, Lm13 of gene LMOf2365_2721 and Lm20 of gene mpl showed better specificity and sensitivity than the primers described previously. The PCR detection limits of the three specific primer sets were 430, 43, 4.3 fg/MUL for genomic DNA, and 5 * 10(3), 50, 5 cfu/mL for pure culture of L. monocytogenes. There was no interference in specificity of detecting L. monocytogenes by co-culture with other foodborne pathogens in high concentration. Moreover, after 6-8 h of enrichment, L. monocytogenes in the artificially contaminated milk samples at an inoculum dose of 38 cfu/10 mL milk could be detected successfully with the studied three primers. Therefore, the three specific genes and primers can be applied to establish a novel rapid and accurate method for detecting L. monocytogenes in food materials. PMID- 26354020 TI - Laccase activity is proportional to the abundance of bacterial laccase-like genes in soil from subtropical arable land. AB - Laccase enzymes produced by both soil bacteria and fungi play important roles in refractory organic matter turnover in terrestrial ecosystems. We investigated the abundance and diversity of fungal laccase genes and bacterial laccase-like genes in soil from subtropical arable lands, and identified which microbial group was associated with laccase activity. Compared with fungal laccase genes, the bacterial laccase-like genes had greater abundance, richness and Shannon-Wiener diversity. More importantly, laccase activity can be explained almost exclusively by the bacterial laccase-like genes, and their abundance had significant linear relationship with laccase activity. Thus, bacterial laccase-like gene has great potential to be used as a sensitive indicator of laccase enzyme for refractory organic matter turnover in subtropical arable lands. PMID- 26354021 TI - Mechanisms of Cancer Cell Dormancy--Another Hallmark of Cancer? AB - Disease relapse in cancer patients many years after clinical remission, often referred to as cancer dormancy, is well documented but remains an incompletely understood phenomenon on the biologic level. Recent reviews have summarized potential models that can explain this phenomenon, including angiogenic, immunologic, and cellular dormancy. We focus on mechanisms of cellular dormancy as newer biologic insights have enabled better understanding of this process. We provide a historical context, synthesize current advances in the field, and propose a mechanistic framework that treats cancer cell dormancy as a dynamic cell state conferring a fitness advantage to an evolving malignancy under stress. Cellular dormancy appears to be an active process that can be toggled through a variety of signaling mechanisms that ultimately downregulate the RAS/MAPK and PI(3)K/AKT pathways, an ability that is preserved even in cancers that constitutively depend on these pathways for their growth and survival. Just as unbridled proliferation is a key hallmark of cancer, the ability of cancer cells to become quiescent may be critical to evolving malignancies, with implications for understanding cancer initiation, progression, and treatment resistance. PMID- 26354022 TI - Validation of ethnopharmacological uses of Murraya paniculata in disorders of diarrhea, asthma and hypertension. AB - BACKGROUND: Murraya paniculata is traditionally used for management of gut, air way and cardiovascular disorders. The study was conducted for provision of pharmacological rationalization for folkloric uses of Murraya paniculata in gut, air way and cardiovascular problems. METHODS: Aqueous-ethanolic extract of Mp.Cr was tested using in vitro techniques on isolated tissue of rabbit (jejunum, trachea and aorta) to detect the possible presence of spasmolytic activity. The responses of tissues were recorded using isotonic transducers coupled with PowerLab data acquisition system. RESULTS: Application of the extract of Mp.Cr relaxed spontaneous and high K(+) (80mM)-induced contraction in rabbit jejunum preparation. Because it shifted the CRCs (Calcium response curve) towards the right side so the possible blockade was of calcium channel similar to verapamil. In rabbit trachea, extract of Mp.Cr produced relaxation of carbachol and high K(+) induced contractions. When plant extract was checked further on isolated aorta for its possible vasodilator effect, it caused relaxation of phenylephrine and high K(+)-induced spastic contractions at different doses. CONCLUSION: These results indicate that Murraya paniculata shows anti-spasmodic, bronchodilator and vasodilator activity facilitated through Ca(++) antagonist mechanisms. PMID- 26354023 TI - Traumatic Life Events and Psychopathology in a High Risk, Ethnically Diverse Sample of Young Children: A Person-Centered Approach. AB - Studies of the association between traumatic experiences and psychopathology in early childhood have primarily focused on specific types of events (e.g., sexual abuse) or aggregated different types of events without differentiating among them. We extend this body of work by investigating patterns of traumatic event exposure in a high-risk, ethnically diverse sample of children ages 3-6 (N = 211; 51 % female) and relating these different patterns to parents' reports of child externalizing, internalizing, and post-traumatic stress symptomatology. Using latent class analysis, which divides a heterogeneous population into homogenous subpopulations, we identified three patterns of traumatic events based on parents' responses to an interview-based assessment of trauma exposure in young children: (1) severe exposure, characterized by a combination of family violence and victimization; (2) witnessing family violence without victimization; and (3) moderate exposure, characterized by an absence of family violence but a moderate probability of other events. The severe exposure class exhibited elevated internalizing and post-traumatic stress symptoms relative to the witness to violence and moderate exposure classes, controlling for average number of traumatic events. Results highlight the need for differentiation between profiles of traumatic life event exposure and the potential for person-centered methods to complement the cumulative risk perspective. PMID- 26354025 TI - Efficacy of etanercept for treating the active rheumatoid arthritis: an updated meta-analysis. AB - AIM: To evaluate the efficacy of etanercept (ETA) for treating active rheumatoid arthritis (RA) compared to placebo or methotrexate (MTX). METHODS: We searched Medline, Cochrane Library and Wiley databases. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated to compare efficacy. RESULTS: In total, 12 studies with 3878 active RA patients (including 2046 patients treated with ETA and 1832 patients treated with placebo or MTX) were included. The overall RRs in ACR20, 50 and 70 (20%, 50%, 70% improvement based on the criteria of American Rheumatism Association) were 2.10 (95% CI: 1.45-3.02, P < 0.0001), 2.87 (95% CI: 1.66-4.97, P = 0.0002) and 2.16 (95% CI: 1.49-3.13, P < 0.0001) within 24 weeks, respectively and were 1.19 (95% CI: 1.11-1.28, P < 0.00001), 1.37 (95% CI: 1.22-1.53, P < 0.00001) and 1.57 (95% CI: 1.28-1.92, P < 0.00001) within 1-3 years, respectively. Further, the overall RRs of 25 mg versus 10 mg ETA twice weekly in ACR20, 50 and 70 were 1.10 (95% CI: 1.02-1.19, P < 0.02), 1.37 (95% CI: 0.98-1.92, P < 0.07) and 1.27 (95% CI: 1.02-1.58, P < 0.03), respectively. CONCLUSIONS: In active RA patients treated with ETA, there was significantly higher efficacy compared to the treatment of placebo or MTX. High doses of ETA were more effective for active RA patients. PMID- 26354024 TI - Systematic stereoscopic analyses for cloacal development: The origin of anorectal malformations. AB - The division of the embryonic cloaca is the most essential event for the formation of digestive and urinary tracts. The defective development of the cloaca results in anorectal malformations (ARMs; 2-5 per 10,000 live births). However, the developmental and pathogenic mechanisms of ARMs are unclear. In the current study, we visualized the epithelia in the developing cloaca and nephric ducts (NDs). Systemic stereoscopic analyses revealed that the ND-cloaca connection sites shifted from the lateral-middle to dorsal-anterior part of the cloaca during cloacal division from E10.5 to E11.5 in mouse embryos. Genetic cell labeling analyses revealed that the cells in the ventral cloacal epithelium in the early stages rarely contributed to the dorsal part. Moreover, we revealed the possible morphogenetic movement of endodermal cells within the anterior part of the urogenital sinus and hindgut. These results provide the basis for understanding both cloacal development and the ARM pathogenesis. PMID- 26354026 TI - Mortality from contact-related epidemics among indigenous populations in Greater Amazonia. AB - European expansion and contact with indigenous populations led to catastrophic depopulation primarily through the introduction of novel infectious diseases to which native peoples had limited exposure and immunity. In the Amazon Basin such contacts continue to occur with more than 50 isolated indigenous societies likely to make further contacts with the outside world in the near future. Ethnohistorical accounts are useful for quantifying trends in the severity and frequency of epidemics through time and may provide insight into the likely demographic consequences of future contacts. Here we compile information for 117 epidemics that affected 59 different indigenous societies in Greater Amazonia and caused over 11,000 deaths between 1875 and 2008, mostly (75%) from measles, influenza, and malaria. Results show that mortality rates from epidemics decline exponentially through time and, independently, with time since peaceful contact. The frequency of documented epidemics also decreases with time since contact. While previous work on virgin soil epidemics generally emphasizes the calamity of contacts, we focus instead on improvements through time. The prospects for better survivorship during future contacts are good provided modern health care procedures are implemented immediately. PMID- 26354027 TI - Microwave-Assisted Syntheses in Recyclable Ionic Liquids: Photoresists Based on Renewable Resources. AB - The copoly(2-oxazoline) pNonOx80 -stat-pDc(=) Ox20 can be synthesized from the cationic ring-opening copolymerization of 2-nonyl-2-oxazoline NonOx and 2-dec-9' enyl-2-oxazoline Dc(=) Ox in the ionic liquid n-hexyl methylimidazolium tetrafluoroborate under microwave irradiation in 250 g/batch quantities. The polymer precipitates upon cooling, enabling easy recovery of the polymer and the ionic liquid. Both monomers can be obtained from fatty acids from renewable resources. pNonOx80 -stat-pDc(=) Ox20 can be used as polymer in a photoresist (resolution of 1 MUm) based on UV-induced thiol-ene reactions. PMID- 26354028 TI - Pharyngeal Tube Flap and Palatoglossal Rotation Flap in Subtotal Soft Palate Reconstruction. AB - Reconstruction of the soft plate after oncologic resection is complex owing to the palate's complex role in speech and swallow. This challenge becomes more complex as defects increase in size. Current management of soft plate reconstruction includes obturation as well as local or microvascular flaps. These methods, though, are limited by poor function and complexity. In regard to large subtotal central soft palate defects, we expand on previous descriptions of a tubed posterior pharyngeal constrictor flap to include a palatoglossal rotational flap that is facile and hardy and has a decreased recovery time. Furthermore, we present 2 representative cases, including 1 with previous radiation, in which our technique was utilized with successful closure of the defect and without subsequent breakdown. PMID- 26354029 TI - "Beaned": A 5-Year Analysis of Baseball-Related Injuries of the Face. AB - OBJECTIVES: Baseball remains one of the most popular and safest games played by children and adults in America and worldwide. Rules and equipment changes have continued to make the game safer. For youth leagues, pitching restrictions, safety balls, helmets, and face mask equipment continue to make the game safer. With increased utilization of safety equipment, the objective was to analyze recent trends in baseball-related facial injuries. STUDY DESIGN: Cross-sectional analysis of a national database. METHODS: The National Electronic Injury Surveillance System was searched for baseball-related facial injuries with analysis of incidence, age, and sex and specific injury diagnoses, mechanisms, and facial locations. RESULTS: From 2009 to 2013, there were 5270 cases entries, or 187,533 estimated emergency department (ED) visits, due to baseball-related facial injuries. During this time, there was a significant decline in the incidence of ED visits (P = .014). Inclusion criteria were met by 3208 visits. The majority of injuries occurred in patients <=18 years old (81.5%). The most common injury was laceration (33.2%), followed by contusion (29.7%) and fracture (26.9%), while the most common injury site on the face was the nose (24.9%). The injuries were most commonly due to impact from a baseball (70%) or a bat (12.5%). CONCLUSION: The overall incidence of ED visits due to baseball-related facial injuries has decreased over the past 5 years, concurrent with increased societal use of protective equipment. Nonetheless, these injuries remain a common source for ED visits, and a continued effort to utilize safety measures should be made, particularly in youth leagues. PMID- 26354030 TI - Corrigendum. PMID- 26354031 TI - Can the intraoperative leak test prevent postoperative leakage of esophagojejunal anastomosis after total gastrectomy? AB - PURPOSE: Anastomotic failures that cannot be detected during surgery often lead to postoperative leakage. There have been no detailed reports on the intraoperative leak test for esophagojejunal anastomosis. Our purpose was to investigate the utility of routine intraoperative leak testing to prevent postoperative anastomotic leakage after performing esophagojejunostomy. METHODS: We prospectively performed routine air leak tests and reviewed the records of 185 consecutive patients with gastric cancer who underwent open total gastrectomy followed by esophagojejunostomy. RESULTS: A positive leak test was found for six patients (3.2 %). These patients with positive leak tests were subsequently treated with additional suturing, and they developed no postoperative anastomotic leakage. However, anastomotic leakage occurred in nine patients (4.9 %) with negative leak tests. A multivariate analysis demonstrated that a patient age >75 years and the surgeon's experience <30 cases were risk factors for anastomotic leakage. CONCLUSION: Intraoperative leak testing can detect some physical dehiscence, and additional suturing may prevent anastomotic leakage. However, it cannot prevent all anastomotic leakage caused by other factors, such as the surgeons' experience and patients' age. PMID- 26354032 TI - Europe's refugee crisis: an urgent call for moral leadership. PMID- 26354033 TI - Cytidine deaminase polymorphisms and worse treatment response in normal karyotype AML. AB - The cytidine deaminase (CDA) catalyzes the irreversible hydrolytic deamination of the cytarabine (AraC) into a 1-beta-D-arabinofuranosyluracil (AraU), an inactive metabolite that plays a crucial role in lowering the amount of AraC, a key chemotherapeutic drug, in the treatment of patients with acute myeloid leukemia (AML). In this study, we hypothesized that CDA polymorphisms were associated with the AraC metabolism for AML treatment and/or related clinical phenotypes. We analyzed 16 polymorphisms of CDA among 50 normal karyotype AML (NK-AML) patients, 45 abnormal karyotype AML (AK-AML) patients and 241 normal controls (NC). Several polymorphisms and haplotypes, rs532545, rs2072671, rs471760, rs4655226, rs818194 and CDA-ht3, were found to have a strong correlation with NK-AML compared with NC and these polymorphisms also revealed strong linkage disequilibrium with each other. Among them, rs2072671 (79A>C), which is located in a coding region and the resultant amino acid change K27Q, showed significant associations with NK-AML compared with NC (P=0.009 and odds ratio=2.44 in the dominant model). The AC and CC genotypes of rs2072671 (79A>C) were significantly correlated with shorter overall survival rates (P=0.03, hazard ratio=1.84) and first complete remission duration (P=0.007, hazard ratio=3.24) compared with the AA genotype in the NK-AML patients. Our results indicate that rs2072671 in CDA may be an important prognostic marker in NK-AML patients. PMID- 26354034 TI - De novo KIF1A mutations cause intellectual deficit, cerebellar atrophy, lower limb spasticity and visual disturbance. AB - Recently, de novo KIF1A mutations were identified in patients with intellectual disability, spasticity and cerebellar atrophy and/or optic nerve atrophy. In this study, we analyzed a total of 62 families, including 68 patients with genetically unsolved childhood cerebellar atrophy, by whole-exome sequencing (WES). We identified five de novo missense KIF1A mutations, including only one previously reported mutation (p.Arg316Trp). All the mutations are located in the motor domain of KIF1A. In all patients, initial symptom onset was during the infantile period, and included developmental delay in three patients and gait disturbance in two. Thereafter, they showed gait disturbances, exaggerated deep tendon reflexes, cerebellar symptoms and cerebellar atrophy on brain magnetic resonance imaging. Four patients showed lower limb spasticity, upper limb clumsiness and visual disturbances. Nerve conduction study revealed peripheral neuropathy in three patients. This study further delineates clinical features of de novo KIF1A mutations. Genetic testing of KIF1A should be considered in children with developmental delay, cerebellar atrophy and pyramidal features. PMID- 26354035 TI - 625 kb microduplication at Xp22.12 including RPS6KA3 in a child with mild intellectual disability. AB - Here, we report on a patient with a 625 kb duplication in Xp22.12, detected by array comparative genomic hybridization (CGH). The duplicated region contains only one gene, RPS6KA3, that results in partial duplication. The same duplication was present in his mother and his maternal uncle. This partial duplication inhibits the RPS6KA3 expression, mimicking the effect of loss-of-function mutations associated with Coffin-Lowry syndrome (CLS). The phenotype of the patient here presented is not fully evocative of this syndrome because he does not present some of the facial, digital and skeletal abnormalities that are considered the main diagnostic features of CLS. This case is one of the few examples where RPS6KA3 mutations are associated with a non-specific X-linked mental retardation. PMID- 26354036 TI - Clinical impact of wordless picture storybooks on bilingual narrative language production: A comparison of the 'Frog' stories. AB - BACKGROUND: Language sampling, recognized as a gold standard for expressive language assessment, is often elicited using wordless picture storybooks. A series of wordless storybooks, commonly referred to as 'Frog' stories, have been frequently used in language-based research with children from around the globe. AIMS: To examine the impact that differences in stories have on narrative output by comparing narrative productions across a series of five storybooks produced by 831 bilingual (Spanish-English) children in kindergarten through third grade. METHODS & PROCEDURES: Each participant produced oral narratives using one of the five Frog storybooks in both English and Spanish. The narratives were recorded, transcribed and coded for a variety of measures of language production. OUTCOMES & RESULTS: Negligible differences were observed in language measures when comparing groups of children who told different stories, with the exception of lexical diversity. CONCLUSIONS & IMPLICATIONS: The implications of using different storybooks to elicit narrative language samples from children are discussed from the perspectives of research and clinical practice. PMID- 26354038 TI - Causes of Death in Adults with Mitochondrial Disease. AB - INTRODUCTION: Mitochondrial diseases are a clinically, biochemically and genetically heterogeneous group of disorders with a variable age of onset and rate of disease progression. It might therefore be expected that this variation be reflected in the age and cause of death. However, to date, little has been reported regarding the 'end-of-life' period and causes of death in mitochondrial disease patients. For some specific syndromes, the associated clinical problems might predict the cause of death, but for many patients, it remains difficult to provide an accurate prognosis. AIMS: To describe a retrospective cohort of adult mitochondrial disease patients who had attended the NHS Highly Specialised Services for Rare Mitochondrial Diseases in Newcastle upon Tyne (UK), evaluate life expectancy and causes of death and assess the consequences for daily patient care. METHODS: All deceased adult patients cared for at this centre over a period of 10 years were included in the study. Patient history, data on laboratory findings, biochemical investigations and genetic studies were analysed retrospectively. RESULTS: A total of 30 adult mitochondrial patients died within the time period of the study. The main mitochondrial disease-related causes of death in this patient cohort were respiratory failure, cardiac failure and acute cerebral incidents such as seizures and strokes. In almost half of the patients, the cause of death remained unknown. Based on our study, we present recommendations regarding the care of patients with mitochondrial disease. PMID- 26354037 TI - Generation of gene-modified goats targeting MSTN and FGF5 via zygote injection of CRISPR/Cas9 system. AB - Recent advances in the study of the CRISPR/Cas9 system have provided a precise and versatile approach for genome editing in various species. However, the applicability and efficiency of this method in large animal models, such as the goat, have not been extensively studied. Here, by co-injection of one-cell stage embryos with Cas9 mRNA and sgRNAs targeting two functional genes (MSTN and FGF5), we successfully produced gene-modified goats with either one or both genes disrupted. The targeting efficiency of MSTN and FGF5 in cultured primary fibroblasts was as high as 60%, while the efficiency of disrupting MSTN and FGF5 in 98 tested animals was 15% and 21% respectively, and 10% for double gene modifications. The on- and off-target mutations of the target genes in fibroblasts, as well as in somatic tissues and testis of founder and dead animals, were carefully analyzed. The results showed that simultaneous editing of several sites was achieved in large animals, demonstrating that the CRISPR/Cas9 system has the potential to become a robust and efficient gene engineering tool in farm animals, and therefore will be critically important and applicable for breeding. PMID- 26354039 TI - "Police Wouldn't Give You No Help": Female Offenders on Reporting Sexual Assault to Police. AB - Sexual assault remains one of the most underreported violent crimes. When victims report, they often are dissatisfied with the police response. The factors influencing one's decision to invoke the law have been widely examined. However, less research examines (a) how the victim's criminality affects this decision and (b) women offenders' characterization of their reporting decisions. We use mixed methods to explore the factors related to an offender's decision to report sexual victimization to police and consider their descriptions of police response when they do report the crime. Our findings provide insight into the gendered relations between offenders and police. PMID- 26354040 TI - Novel analytical approach for brominated flame retardants based on the use of gas chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry with emphasis in highly brominated congeners. AB - The analysis of brominated flame retardants (BFRs) commonly relies on the use of gas chromatography coupled to mass spectrometry (GC-MS) operating in electron ionization (EI) and electron capture negative ionization (ECNI) modes using quadrupole, triple quadrupole, ion trap, and magnetic sector analyzers. However, these brominated contaminants are examples of compounds for which a soft and robust ionization technique might be favorable since they show high fragmentation in EI and low specificity in ECNI. In addition, the low limits of quantification (0.01 ng/g) required by European Commission Recommendation 2014/118/EU on the monitoring of traces of BFRs in food put stress on the use of highly sensitive techniques/methods. In this work, a new approach for the extremely sensitive determination of BFRs taking profit of the potential of atmospheric pressure chemical ionization (APCI) combined with GC and triple quadrupole (QqQ) mass analyzer is proposed. The objective was to explore the potential of this approach for the BFRs determination in samples at pg/g levels, taking marine samples and a cream sample as a model. Ionization and fragmentation behavior of 14 PBDEs (congeners 28, 47, 66, 85, 99, 100, 153, 154, 183, 184, 191, 196, 197, and 209) and two novel BFRs, decabromodiphenyl ethane (DBDPE) and 1,2-bis(2,4,6 tribromophenoxy)ethane (BTBPE), in the GC-APCI-MS system has been investigated. The formation of highly abundant (quasi) molecular ion was the main advantage observed in relation to EI. Thus, a notable improvement in sensitivity and specificity was observed when using it as precursor ion in tandem MS. The improved detectability (LODs < 10 fg) achieved when using APCI compared to EI has been demonstrated, which is especially relevant for highly brominated congeners. Analysis of samples from an intercomparison exercise and samples from the marine field showed the potential of this approach for the reliable identification and quantification at very low concentration levels. PMID- 26354041 TI - Influence of different lubricants on the retentive force of LOCATOR((r)) attachments - an in vitro pilot study. AB - OBJECTIVE: The aim of this in vitro pilot study was to evaluate the influence of an artificial saliva (AS) lubricant on the retentive force of a stud-type attachment (LOCATOR((r)) ) for implant overdentures (IODs). METHODS: Twenty custom-made models simulating a two-IOD with parallel implant situation were fabricated using LOCATOR((r)) attachments. The in vitro testing was carried out with an Instron((r)) universal testing machine for a total of 10,000 insertion removal cycles, for each model, in two different aqueous test mediums (Group 1: 0.9% sodium chloride solution (NaCl), n = 10; Group 2: AS, n = 10). Changes in the mean retentive force (F) were plotted against the cycle numbers #10, #100, #1000, #5000, and #10,000. Mixed regression models were applied for statistical analyses. RESULTS: A mixed regression (not considering interactions) predicted, compared to cycle #10, higher retentive forces at cycles #100 (P < 0.0001), #1000 (P = 0.017), similar forces at #5000 (P = 0.277), and lower forces at #10,000 (P = 0.012); there was no overall effect of the medium (P = 0.159). A second statistical model, employing the interaction term "cycle##medium", confirmed similarly the effect. Although the interaction term was significant at cycle #100 (p = 0.045), there was no significant difference between the two groups (P = 0.140). CONCLUSION: In this in vitro pilot experiment, there was no difference in mean retentive forces of the LOCATOR((r)) attachments when tested with either 0.9% NaCl or a Glandosane((r)) -like artificial saliva lubricant. A larger scale study may still confirm the superiority of either lubricant for quasiclinical bench experiments. PMID- 26354042 TI - Cation influence on exciton localization in homologue scheelites. AB - Homologue scheelite crystals CaWO4, SrWO4, and BaWO4 possess similar crystal and electronic structure, but their luminescence exhibits drastically different thermal stabilities. By measuring the temperature dependence of the decay time of the intrinsic luminescence and fitting it to a three level model, we have qualitatively shown the effective exciton radius to increase in the order CaWO4 > SrWO4 -> BaWO4, which explains the differences in the thermal stability. The origin of the variation in the exciton radii is suggested to be related to differences in the excited state dynamics in these crystals. From the decay kinetics measured under conditions of high excitation density, the efficiency of dipole-dipole interaction between excitons is shown to grow with exciton delocalization. PMID- 26354043 TI - Enhanced Glutamatergic Synaptic Plasticity in the Hippocampal CA1 Field of Food Restricted Rats: Involvement of CB1 Receptors. AB - The endogenous endocannabinoid system has a crucial role in regulating appetite and feeding behavior in mammals, as well as working memory and reward mechanisms. In order to elucidate the possible role of cannabinoid type-1 receptors (CB1Rs) in the regulation of hippocampal plasticity in animals exposed to food restriction (FR), we limited the availability of food to a 2-h daily period for 3 weeks in Sprague-Dawley rats. FR rats showed a higher long-term potentiation at hippocampal CA1 excitatory synapses with a parallel increase in glutamate release when compared with animals fed ad libitum. FR rats showed a significant increase in the long-term spatial memory determined by Barnes maze. FR was also associated with a decreased inhibitory effect of the CB1R agonist win55,212-2 on glutamatergic field excitatory postsynaptic potentials, together with a decrease in hippocampal CB1R protein expression. In addition, hippocampal brain-derived neurotrophic factor protein levels and mushroom dendritic spine density were significantly enhanced in FR rats. Altogether, our data suggest that alterations of hippocampal CB1R expression and function in FR rats are associated with dendritic spine remodeling and functional potentiation of CA1 excitatory synapses, and these findings are consistent with increasing evidence supporting the idea that FR may improve cognitive functions. PMID- 26354044 TI - Selective Control of Fear Expression by Optogenetic Manipulation of Infralimbic Cortex after Extinction. AB - Evidence from rodent and human studies has identified the ventromedial prefrontal cortex, specifically the infralimbic cortex (IL), as a critical brain structure in the extinction of conditioned fear. However, how IL activity controls fear expression at the time of extinction memory retrieval is unclear and controversial. To address this issue, we used optogenetics to precisely manipulate the activity of genetically targeted cells and to examine the real time contribution of IL activity to expression of auditory-conditioned fear extinction in mice. We found that inactivation of IL, but not prelimbic cortex, impaired extinction retrieval. Conversely, photostimulation of IL excitatory neurons robustly enhanced the inhibition of fear expression after extinction, but not before extinction. Moreover, this effect was specific to the conditioned stimulus (CS): IL activity had no effect on expression of fear in response to the conditioned context after auditory fear extinction. Thus, in contrast to the expectation from a generally held view, artificial activation of IL produced no significant effect on expression of non-extinguished conditioned fear. Therefore, our data provide compelling evidence that IL activity is critical for expression of fear extinction and establish a causal role for IL activity in controlling fear expression in a CS-specific manner after extinction. PMID- 26354045 TI - Alterations in High-Frequency Neuronal Oscillations in a Cynomolgus Macaque Test of Sustained Attention Following NMDA Receptor Antagonism. AB - A growing body of evidence indicates that neuronal oscillations in the gamma frequency range (30-80 Hz) are disturbed in schizophrenic patients during cognitive processes and may represent an endophenotype of the disease. N-methyl-D aspartate (NMDA) receptor antagonists have been used experimentally to induce schizophrenia-like symptoms including cognitive deficits in animals and humans. Here we characterized neuronal oscillations and event-related potentials (ERPs) in Cynomolgus macaques fully trained to perform a continuous performance test (CPT) in the presence and absence of the NMDA antagonist phencyclidine (PCP). Macaques (n=8) were trained to touch 'target' stimuli and ignore 'distractor' stimuli presented randomly on a touchscreen. Subsequently, all subjects were implanted with epidural EEG electrodes over frontal (FC) and parietal cortices (PC) and later tested under vehicle (saline, i.m.) or acute PCP (0.1-0.3 mg/kg, i.m.) conditions. Compared with vehicle treatment, PCP produced a significant dose-dependent decrease in CPT performance accuracy and increased reaction times. Furthermore, PCP elevated the amplitudes of 'low' (30-50 Hz) and 'high' (51-80 Hz) gamma oscillations in FC and PC around target presentations for all correct responses. The CPT accuracy was inversely correlated with the gamma band amplitude in the presence of PCP. Additionally, PCP delayed the N100 peak latency in FC, and prolonged and suppressed the cognitively relevant P300 component of mean ERPs in FC and PC, respectively. The NMDA receptor antagonist-induced alteration in neuronal oscillations and ERPs may contribute to the observed cognitive deficits in macaques, and enhance our understanding of EEG recordings as a translatable biomarker. PMID- 26354047 TI - Synthesis of alpha-Chiral Butyrolactones by Highly Stereoselective Radical Transfer or Sequential Asymmetric Alkylations: Concise Preparation of Leupyrrin Moieties. AB - Inspired by the bioactive natural metabolites leupyrrin A1 and B1 , two novel stereoselective methods for the highly concise synthesis of densely substituted alpha-chiral butyrolactones are reported. The first approach relies on an innovative three-step Ti(III) -catalyzed radical reaction that proceeds with excellent chemo-, regio-, and stereoselectivity. The alternative route utilizes sequential asymmetric alkylations and enables asymmetric synthesis of the authentic alpha-tetrasubstituted butyrolactone motif of the leupyrrins in only four steps from commercially available substrates. PMID- 26354046 TI - Neural Dysfunction in Cognitive Control Circuits in Persons at Clinical High-Risk for Psychosis. AB - Cognitive control, a set of functions that develop throughout adolescence, is important in the pathogenesis of psychotic disorders. Whether cognitive control has a role in conferring vulnerability for the development of psychotic illness is still unknown. The aim of this study was to investigate the neural systems supporting cognitive control in individuals deemed to be potentially prodromal for psychotic illness. We recruited 56 participants at clinical high-risk (CHR) for psychosis based on the Structured Interview for Psychosis-Risk Syndromes (SIPS) and 49 healthy controls. Twelve of the CHR participants eventually developed psychosis. We compared functional magnetic resonance imaging (fMRI) BOLD signal during the performance of the Simon task. We tested for differences between CHR individuals and controls in conflict-related functional activity. In the CHR group when compared with controls, we detected smaller conflict-related activations in several cortical areas, including the Dorsolateral Prefrontal Cortex (DLPFC). Furthermore, conflict-related activations in the DLPFC of those CHR individuals who ultimately developed psychosis (CHR converters) were smaller than in non-converters (CHR non-converters). Higher levels of conflict-related activation were associated with better social and role outcome. Risk for psychosis was associated at the neural level with reduced conflict-related brain activity. This neural phenotype appears correlated within the DLPFC with the development of psychosis and with functional outcome. PMID- 26354048 TI - Advancing Best Practices for Prescription Drug Labeling. AB - OBJECTIVE: Problematic prescription drug labeling has been cited as a root cause of patient misunderstanding, medication errors, and nonadherence. Although numerous studies have recently been conducted to identify and test labeling best practices, the last systematic review on this topic was conducted a decade ago. The objective of this review was, therefore, to examine, summarize, and update best practices for conveying written prescription medication information and instructions to patients. DATA SOURCES: English-language articles published from June 2005 to June 2015 were identified in MEDLINE and CINAHL by searching the following text words: 'medication OR prescription OR drug' AND 'label OR leaflet OR brochure OR pamphlet OR medication guide OR medication insert OR drug insert OR medication information OR drug information OR instructions' AND 'patient OR consumer.' Reference mining and secondary searches were also performed. STUDY SELECTION AND DATA EXTRACTION: A total of 31 articles providing evidence on how to improve written, prescription drug labeling for patient use were selected. Two reviewers independently screened articles, rated their quality, and abstracted data. DATA SYNTHESIS: Identified best practices included the use of plain language, improved formatting and organization, and more explicit instructions to improve patient comprehension. The use of icons had conflicting findings, and few studies tested whether practices improved knowledge or behaviors with patients' actual prescribed regimens. CONCLUSIONS: Future studies are needed to determine how specific modifications and improvements in drug labeling can enhance patient knowledge and behavior in actual use. Synthesizing best practices across all patient materials will create a more useful, coordinated system of prescription information. PMID- 26354049 TI - A systematic approach for the diagnosis and treatment of idiopathic peptic ulcers. AB - An idiopathic peptic ulcer is defined as an ulcer with unknown cause or an ulcer that appears to arise spontaneously. The first step in treatment is to exclude common possible causes, including Helicobacter pylori infection, infection with other pathogens, ulcerogenic drugs, and uncommon diseases with upper gastrointestinal manifestations. When all known causes are excluded, a diagnosis of idiopathic peptic ulcer can be made. A patient whose peptic ulcer is idiopathic may have a higher risk for complicated ulcer disease, a poorer response to gastric acid suppressants, and a higher recurrence rate after treatment. Risk factors associated with this disease may include genetic predisposition, older age, chronic mesenteric ischemia, smoking, concomitant diseases, a higher American Society of Anesthesiologists score, and higher stress. Therefore, the diagnosis and management of emerging disease should systematically explore all known causes and treat underlying disease, while including regular endoscopic surveillance to confirm ulcer healing and the use of proton-pump inhibitors on a case-by-case basis. PMID- 26354050 TI - Evidence for beneficial effects of vitamin E. AB - Oxidative stress and lipid peroxidation have been implicated in the pathogenesis of various diseases, including atherosclerosis and fatty liver diseases, and consequently the role of antioxidants in the prevention and treatment of such diseases has received much attention. In particular, the effects of vitamin E, the most important lipophilic radical-scavenging antioxidant, have been investigated extensively. Many in vitro, animal, and epidemiological studies have reported positive results, but large-scale randomized controlled intervention studies and meta-analyses have produced inconsistent and often disappointing results. In the present review article, the role and action of vitamin E are discussed, with consideration of the factors that determine the outcome of vitamin E treatment. Vitamin E should benefit subjects experiencing oxidative stress due to free radicals when administered at the correct time and for an appropriate duration. PMID- 26354052 TI - Detecting masked high blood pressure in high-risk patients. PMID- 26354051 TI - Mesenchymal stem cell therapy for liver fibrosis. AB - Currently, the most effective treatment for end-stage liver fibrosis is liver transplantation; however, transplantation is limited by a shortage of donor organs, surgical complications, immunological rejection, and high medical costs. Recently, mesenchymal stem cell (MSC) therapy has been suggested as an effective alternate approach for the treatment of hepatic diseases. MSCs have the potential to differentiate into hepatocytes, and therapeutic value exists in their immune modulatory properties and secretion of trophic factors, such as growth factors and cytokines. In addition, MSCs can suppress inflammatory responses, reduce hepatocyte apoptosis, increase hepatocyte regeneration, regress liver fibrosis and enhance liver functionality. Despite these advantages, issues remain; MSCs also have fibrogenic potential and the capacity to promote tumor cell growth and oncogenicity. This paper summarizes the properties of MSCs for regenerative medicine and their therapeutic mechanisms and clinical application in the treatment of liver fibrosis. We also present several outstanding risks, including their fibrogenic potential and their capacity to promote pre-existing tumor cell growth and oncogenicity. PMID- 26354053 TI - Can proton pump inhibitors reduce rebleeding following Histoacryl sclerotherapy for gastric variceal hemorrhage? AB - BACKGROUND/AIMS: To evaluate the efficacy of proton pump inhibitors (PPIs) in reducing rebleeding and bleeding-related death rates after endoscopic gastric variceal obliteration (GVO) using N-butyl-2-cyanoacrylate (NBC). METHODS: This study enrolled 341 patients who were consecutively diagnosed with and treated for bleeding gastric varices. The patients were divided into PPI and non-PPI groups, and their endoscopic findings, initial hemostasis outcomes, rebleeding and bleeding-related death rates, and treatment-related complications were analyzed. RESULTS: The rate of initial hemostasis was 97.1%. rebleeding occurred in 2.2% of patients within 2 weeks, 3.9% of patients within 4 weeks, 18.9% of patients within 6 months, and 27.6% of patients within 12 months of the GVO procedure. A previous history of variceal bleeding (relative risk [RR], 1.955; 95% confidence interval [CI], 1.263 to 3.028; p = 0.003) and use of PPIs (RR, 0.554; 95% CI, 0.352 to 0.873; p = 0.011) were associated with rebleeding. Child-Pugh class C (RR, 10.914; 95% CI, 4.032 to 29.541; p < 0.001), failure of initial hemostasis (RR, 13.329; 95% CI, 2.795 to 63.556; p = 0.001), and the presence of red-colored concomitant esophageal varices (RR, 4.096; 95% CI, 1.320 to 12.713; p = 0.015) were associated with bleeding-related death. CONCLUSIONS: The prophylactic use of PPIs reduces rebleeding after GVO using NBC in patients with gastric variceal hemorrhage. However, prophylactic use of PPIs does not reduce bleeding-related death. PMID- 26354054 TI - Oral udenafil and aceclofenac for the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis in high-risk patients: a randomized multicenter study. AB - BACKGROUND/AIMS: Acute pancreatitis is a common complication of endoscopic retrograde cholangiopancreatography (ERCP). Combination therapy w ith ora l udenafil and aceclofenac may reduce the occurrence of post-ERCP pancreatitis by targeting different pathophysiological mechanisms. We investigated whether combining udenafil and aceclofenac reduced the rates of post-ERCP pancreatitis. METHODS: A prospective, randomized, double-blind, placebo-controlled, multicenter study was conducted in four academic medical centers. Between January 2012 and June 2013, a total of 216 patients who underwent ERCP were analyzed for the occurrence of post-ERCP pancreatitis. Patients were determined to be at high risk for pancreatitis based on validated patient and procedure-related risk factors. RESULTS: Demographic features, indications for ERCP, and therapeutic procedures were similar in each group. There were no significant differences in the rate (15.8% [17/107] vs. 16.5% [18/109], p = 0.901) and severity of post-ERCP pancreatitis between the udenafil/aceclofenac and placebo groups. One patient in each group developed severe pancreatitis. Multivariate analyses indicated that suspected dysfunction of the sphincter of Oddi and endoscopic papillary balloon dilation without sphincterotomy were associated with post-ERCP pancreatitis. CONCLUSIONS: Combination therapy with udenafil and aceclofenac is not effective for the prevention of post-ERCP pancreatitis. PMID- 26354055 TI - Discordance between ambulatory versus clinic blood pressure according to global cardiovascular risk group. AB - BACKGROUND/AIMS: The detection of white coat hypertension (WCH), treated normalized hypertension, and masked hypertension (MH) is important to improve the effectiveness of hypertension management. However, whether global cardiovascular risk (GCR) profile has any effect on the discordance between ambulatory blood pressure (ABP) and clinic blood pressure (CBP) is unknown. METHODS: Data from 1,916 subjects, taken from the Korean Multicenter Registry for ABP monitoring, were grouped according to diagnostic and therapeutic thresholds for CBP and ABP (140/90 and 135/85 mmHg, respectively). GCR was assessed using European Society of Hypertension 2007 guidelines. RESULTS: The mean subject age was 54.1 +/- 14.9 years, and 48.9% of patients were female. The discordancy rate between ABP and CBP in the untreated and treated patients was 32.5% and 26.5%, respectively (p = 0.02). The prevalence of WCH or treated normalized hypertension and MH was 14.4% and 16.0%, respectively. Discordance between ABP and CBP was lower in the very high added-risk group compared to the moderate added-risk group (odds ratio [OR], 0.649; 95% confidence interval [CI], 0.487 to 0.863; p = 0.003). The prevalence of WCH or treated normalized hypertension was also lower in the very high added risk group (OR, 0.451; 95% CI, 0.311 to 0.655). CONCLUSIONS: Discordance between ABP and CBP was observed more frequently in untreated subjects than in treated subjects, and less frequently in the very high added-risk group, which was due mainly to the lower prevalence of WCH or treated normalized hypertension. PMID- 26354056 TI - A pharmacodynamic study of the optimal P2Y12 inhibitor regimen for East Asian patients with acute coronary syndrome. AB - BACKGROUND/AIMS: Newer P2Y12 inhibitors, such as prasugrel and ticagrelor, have greater antiplatelet efficacy but may increase the risk of bleeding. In this study, we compared the pharmacodynamic efficacy of prasugrel and ticagrelor in East Asian patients with acute coronary syndrome (ACS). METHODS: We selected 83 ACS patients undergoing percutaneous coronary intervention who were discharged with 90 mg ticagrelor twice daily (n = 24), 10 mg prasugrel daily (n = 39) or 5 mg prasugrel daily (n = 20). After 2 to 4 weeks, on-treatment platelet reactivity (OPR) was assessed in terms of P2Y12 reaction units (PRUs) using the VerifyNow P2Y12 assay (Accumetrics). We compared East Asian (85 < PRU <= 275) and Caucasian (85 < PRU <= 208) criteria for assessing the therapeutic window of OPR. RESULTS: OPR was lowest in the ticagrelor group, followed by the 10 mg prasugrel and 5 mg prasugrel groups (49.1 +/- 29.9 vs. 83.7 +/- 57.1 vs. 168.5 +/- 60.8, respectively; p < 0.001). The 5 mg prasugrel group had the highest proportion of patients with OPR values within the therapeutic window, followed by the 10 mg prasugrel and ticagrelor groups (90.0% vs. 46.2% vs. 12.5%, respectively; p < 0.001 for East Asian criteria; 60.0% vs. 43.6% vs. 12.5%, respectively; p < 0.001 for Caucasian criteria). CONCLUSIONS: Short-term administration of 5 mg prasugrel facilitated maintenance within the therapeutic window of OPR compared with the 10 mg prasugrel and ticagrelor groups. Thus, 5 mg prasugrel daily may be the optimal antiplatelet regimen for stabilized East Asian ACS patients. PMID- 26354057 TI - Chronic obstructive pulmonary disease (COPD) assessment test scores corresponding to modified Medical Research Council grades among COPD patients. AB - BACKGROUND/AIMS: In assigning patients with chronic obstructive pulmonary disease (COPD) to subgroups according to the updated guidelines of the Global Initiative for Chronic Obstructive Lung Disease, discrepancies have been noted between the COPD assessment test (CAT) criteria and modified Medical Research Council (mMRC) criteria. We investigated the determinants of symptom and risk groups and sought to identify a better CAT criterion. METHODS: This retrospective study included COPD patients seen between June 20, 2012, and December 5, 2012. The CAT score that can accurately predict an mMRC grade >= 2 versus < 2 was evaluated by comparing the area under the receiver operating curve (AUROC) and by classification and regression tree (CART) analysis. RESULTS: Among 428 COPD patients, the percentages of patients classified into subgroups A, B, C, and D were 24.5%, 47.2%, 4.2%, and 24.1% based on CAT criteria and 49.3%, 22.4%, 8.9%, and 19.4% based on mMRC criteria, respectively. More than 90% of the patients who met the mMRC criteria for the 'more symptoms group' also met the CAT criteria. AUROC and CART analyses suggested that a CAT score >= 15 predicted an mMRC grade >= 2 more accurately than the current CAT score criterion. During follow-up, patients with CAT scores of 10 to 14 did not have a different risk of exacerbation versus those with CAT scores < 10, but they did have a lower exacerbation risk compared to those with CAT scores of 15 to 19. CONCLUSIONS: A CAT score >= 15 is a better indicator for the 'more symptoms group' in the management of COPD patients. PMID- 26354058 TI - Clinical characteristics of nursing home-acquired pneumonia in elderly patients admitted to a Korean teaching hospital. AB - BACKGROUND/AIMS: Nursing home-acquired pneumonia (NHAP) is included under healthcare-associated pneumonia. However, the optimal treatment strategy for NHAP has been controversial in several studies. We evaluated the clinical features of NHAP compared to community-acquired pneumonia (CAP) in elderly patients admitted with pneumonia. METHODS: This was a retrospective study in elderly patients aged >= 65 years with NHAP or CAP who were hospitalized at Jeju National University Hospital between January 2012 and April 2013. RESULTS: A total of 209 patients were enrolled, and 58 (27.7%) had NHAP. The patients with NHAP were older, had more frequent central nervous system disorders, and showed worse clinical parameters. Potential drug-resistant pathogens were more frequently detected in the NHAP group (22.4% vs. 9.9%, p = 0.018), and the incidences of Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus were 8.6% and 10.3%, respectively. In-hospital mortality occurred in 13 patients (22.4%) with NHAP and 17 patients (11.2%) with CAP (p = 0.039). In multivariate analyses, only higher pneumonia severity index (PSI) score was associated with increased mortality (p < 0.001), and the PSI score was higher in the NHAP group than that in the CAP group. CONCLUSIONS: Elderly patients admitted with NHAP showed more severe pneumonia at onset, higher rates of potentially drug-resistant pathogens, and worse clinical outcomes than those with CAP. However, higher in-hospital mortality in those with NHAP seemed to be related to the PSI score reflecting host factors and severity of pneumonia rather than the type of pneumonia or the presence of drug-resistant pathogens. PMID- 26354059 TI - Blood electrolyte disturbances during severe hypoglycemia in Korean patients with type 2 diabetes. AB - BACKGROUND/AIMS: To investigate abnormalities in blood electrolyte levels during severe hypoglycemia in Korean patients with type 2 diabetes mellitus (T2DM) in a clinical setting. METHODS: Blood electrolyte levels in adult T2DM patients during severe hypoglycemia were collected from January 1, 2008 to December 31, 2012. Patients who maintained normal serum creatinine and blood urea nitrogen levels were utilized in the study. Severe hypoglycemia was defined as a condition requiring medical assistance, such as administering carbohydrates when serum glucose levels less than 70 mg/dL were observed, in conjunction with other symptoms of hypoglycemia. RESULTS: A total of 1,068 patients who visited the emergency room with severe hypoglycemia were screened, of which 219 patients were included in this study. The incidence of abnormal levels for any electrolyte was 47%. Hypokalemia (< 3.5 mmol/L) was the most common type of electrolyte disturbance observed at 21.9%. A decrease in serum potassium levels was associated with decreases in blood glucose levels (r = 0.151, p = 0.025). During severe hypoglycemia, median blood glucose levels, incidence of tachycardia (> 100 beats per minute) and severe hypertension (>= 180/120 mmHg) were 30 mg/dL (range, 14 to 62) and 35 mg/dL (range, 10 to 69; p = 0.04), 18.8% and 7.2% (p = 0.02), and 20.8% and 10.2% (p = 0.05) in the hypokalemia and normokalemia groups, respectively. CONCLUSIONS: During severe hypoglycemia, hypokalemia occurred in 21.9% of T2DM patients and was associated with tachycardia and severe hypertension. Therefore, the results suggest that severe hypoglycemia may increase cardiovascular events in T2DM. PMID- 26354060 TI - Immunologic and non-immunologic complications of a third kidney transplantation. AB - BACKGROUND/AIMS: Patients who undergo repeat kidney transplantations (KTs) are considered at high risk for experiencing immunologic and non-immunologic complications. In this study, we investigated the clinical outcomes, including medical and surgical complications, of patients who underwent a third KT at our center. METHODS: Between March 1969 and December 2012, a total of 2,110 KTs were performed at the Seoul St. Mary's Hospital. Of them, we examined 11 patients who underwent a third KT, and investigated the allograft outcomes and complication rates. RESULTS: The mean follow-up duration after KT was 72.4 +/- 78.3 months. The mean age at KT was 38.2 +/- 8.0 years, and seven patients (63.6%) were males. Nine patients (81.8%) underwent living-donor KT. A cross-match test yielded positive results in four of the nine patients, and all underwent pretransplant desensitization therapy. After KT, three patients (27.2%) showed delayed graft function. Acute rejection developed in four patients (36.4%), and surgical complications that required surgical correction occurred in three patients. Allograft failure developed due to acute rejection (n = 3) or chronic rejection (n = 1) in four patients. Allograft survival rates at 1, 5, and 10 years were 81.8%, 42.9%, and 42.9%, respectively; however, the allograft survival rate at 5 years was > 80% in patients who underwent KT only after results of the panel reactive antibody test became available. CONCLUSIONS: Thus, a third KT procedure may be acceptable, although aggressive pretransplant immune monitoring and patient selection may be required to reduce the risks of acute rejection and surgical complications. PMID- 26354061 TI - Time points for obtaining representative values of 24-hour blood pressure in chronic kidney disease. AB - BACKGROUND/AIMS: Ambulatory blood pressure (BP) monitoring has been widely recommended for evaluating the status of BP, but is lacking in practicality. Determination of the specific time points for BP measurement that are representative of 24-hour mean BP could be useful and convenient in hypertensive patients with chronic kidney disease (CKD). METHODS: A total of 1,317 patients for whom 24-hour ambulatory BP monitoring was performed were enrolled in a multicenter study on hypertensive CKD. We analyzed the time points at which systolic blood pressure (SBP) values exhibited the smallest differences from 24 hour mean SBP (mSBP). We included office mSBP and analyzed the relationships between SBPs at the office and the time points with the smallest differences from 24-hour mSBP using several methods. RESULTS: The time points with the smallest differences from 24-hour mSBP were 7:00 AM, 2:00 PM, and 9:30 PM. In regression analysis, SBPs at 7:00 AM and 9:30 PM were better correlated with 24-hour mSBP than SBPs at 2:00 PM and the office. The proportions of patients with SBPs within 30% of 24-hour mSBP were higher at 7:00 AM and 9:30 PM. The best consistency between the uncontrolled hypertensive groups, defined as >= 135 mmHg of 24-hour mSBP and higher values of SBPs corresponding to 135 mmHg of 24-hour mSBP, were observed at the 7:00 AM and 9:30 PM time points. CONCLUSIONS: The specific time points for SBPs that correlated well with 24-hour mSBP in hypertensive CKD patients were 7:00 AM and 9:30 PM. PMID- 26354062 TI - The prognostic impact of inflammatory factors in patients with multiple myeloma treated with thalidomide in Korea. AB - BACKGROUND/AIMS: The purpose of this study was to determine the correlations between inflammatory factors-including absolute lymphocyte count, lactate dehydrogenase, beta2-microglobulin, albumin, C-reactive protein, and ferritin-and the prognosis for survival in patients with multiple myeloma (MM) treated with induction chemotherapy containing thalidomide and who underwent autologous stem cell transplantation (ASCT). METHODS: Data from patients at 13 university hospitals in South Korea were collected retrospectively between December 2005 and May 2013. RESULTS: The median age of the 232 patients was 57 years (range, 33 to 77) and the male to female ratio was 1.09:1. In the multivariate analysis, fewer than two combined abnormal inflammatory factors was the only independent prognostic factor for superior progression-free survival (relative risk [RR], 0.618; 95% confidence interval [CI], 0.409 to 0.933; p = 0.022), and platelet count > 100 * 10(9)/L and fewer than two combined abnormal inflammatory factors were independent prognostic factors for superior overall survival (RR, 4.739; 95% CI, 1.897 to 11.839; p = 0.001 and RR, 0.263; 95% CI, 0.113 to 0.612; p = 0.002, respectively). CONCLUSIONS: Patients with two or more than two combined inflammatory factors who were treated with thalidomide induction chemotherapy and who underwent ASCT showed significantly shorter survival compared to those with fewer than two combined inflammatory factors. These results could be helpful for predicting prognosis in patients with MM. PMID- 26354063 TI - Clinical characteristics and outcomes in diffuse large B cell lymphoma patients aged 70 years and older: a single-center experience with a literature review. AB - BACKGROUND/AIMS: Among diffuse large B cell lymphoma (DLBCL) patients, determining the appropriate dose and chemotherapy schedule to balance toxicity and efficacy is harder in elderly than in younger patients. Moreover, there are no currently available clinical factors that consistently identify patients who are unfit to receive chemotherapy. Therefore, the clinical characteristics and outcomes of elderly patients with DLBCL and the causes of treatment-related death were investigated in this study. METHODS: The clinical characteristics and outcomes of 44 elderly (>= 70 years of age) patients diagnosed with DLBCL between January 2005 and June 2013 were evaluated. Variable clinical data along with the response rate, overall survival (OS), and causes of treatment-related death or treatment interruption were investigated. RESULTS: The median OS was 18.6 months, and 19 patients completed curative treatment. The mean average relative dose intensity of adriamycin in patients who completed chemotherapy was 0.617, and of these patients, 16 achieved complete remission. Chemotherapy incompletion, infectious complications, ex tranoda l involvement, high lactate dehydrogenase, poor performance status, and low albumin level at diagnosis were related to a shorter OS. However, multivariate analysis revealed that only infections and chemotherapy incompletion were significantly related to poor prognosis. The most common cause of treatment-related death was infection, and patients who had experienced infectious complications tended to have lower albumin levels than those of patients without such complications. CONCLUSIONS: In the treatment of elderly lymphoma patients, the dose intensity of adriamycin is not as important as it is in young patients. However, in elderly patients, infections are particularly dangerous, especially in patients with low albumin levels. PMID- 26354064 TI - Clinical significance of methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci colonization in liver transplant recipients. AB - BACKGROUND/AIMS: Liver transplant patients are at high risk for methicillin resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) colonization. We evaluated patients before and after liver transplant using active surveillance culture (ASC) to assess the prevalence of MRSA and VRE and to determine the effect of bacterial colonization on patient outcome. METHODS: We performed ASC on 162 liver transplant recipients at the time of transplantation and 7 days posttransplantation to monitor the prevalence of MRSA and VRE. RESULTS: A total of 142 patients had both nasal and rectal ASCs. Of these patients, MRSA was isolated from 12 (7.4%) at the time of transplantation (group 1a), 9 (6.9%) acquired MRSA posttransplantation (group 2a), and 121 did not test positive for MRSA at either time (group 3a). Among the three groups, group 1a patients had the highest frequency of developing a MRSA infection (p < 0.01); however, group 2a patients had the highest mortality rate associated with MRSA infection (p = 0.05). Of the 142 patients, VRE colonization was detected in 37 patients (22.8%) at the time of transplantation (group 1b), 21 patients (20%) acquired VRE posttransplantation (group 2b), and 84 patients did not test positive for VRE at either time (group 3b). Among these three groups, group 2b patients had the highest frequency of VRE infections (p < 0.01) and mortality (p = 0.04). CONCLUSIONS: Patients that acquired VRE or MRSA posttransplantation had higher mortality rates than did those who were colonized pre-transplantation or those who never acquired the pathogens. Our findings highlight the importance of preventing the acquisition of MRSA and VRE posttransplantation to reduce infections and mortality among liver transplant recipients. PMID- 26354065 TI - The CD4 slope can be a predictor of immunologic recovery in advanced HIV patients: a case-control study. AB - BACKGROUND/AIMS: Advanced human immunodeficiency virus (HIV) infection, despite sustained viral suppression by highly active antiretroviral therapy (HAART), is a risk factor for poor immunologic recovery. However, some patients with advanced infection do show immunologic recovery. In this study, predictive factors of immunologic recovery were analyzed in advanced HIV patients showing sustained viral suppression. METHODS: A case-control study was conducted in HIV-infected adult patients with HIV-1 RNA < 50 copies/mL maintained for 4 years or longer and who were receiving HAART. Advanced HIV infection was defined as a baseline CD4 T cell count < 200/mm(3). Immunologic responders were defined as patients showing immunologic recovery (CD4 T cell counts >= 500/mm(3) at 4 years with HAART). To analyze the CD4 T cell kinetics, the CD4 slope (monthly changes in the CD4 T cell count) was estimated for each patient using a linear regression between the CD4 T cell count and the time since HAART initiation. RESULTS: Of 102 eligible patients, 73 had advanced HIV, and 33 (45.2%) showed immunologic recovery. The median CD4 slopes (cells/mm(3) per month) during 0 to 6 and 0 to 12 months of HAART in the 73 advanced patients were significantly higher in responders than in non-responders (0 to 6 months, 38.6 vs. 22.8; 0 to 12 months, 24.5 vs. 13.5). Multivariate analyses showed opportunistic infections at the start of HAART (adjusted odds ratio [OR], 0.28) and a CD4 slope >= 20 during 0 to 12 months of HAART (adjusted OR, 10.10) were independently associated with immunologic recovery. CONCLUSIONS: The CD4 slope can be an early predictor of long-term immunologic recovery in advanced HIV patients. PMID- 26354066 TI - Cross-cultural adaptation and validation of the Behcet's Disease Current Activity Form in Korea. AB - BACKGROUND/AIMS: This study was undertaken to perform a cross-cultural adaptation of the Behcet's Disease Current Activity Form (BDCAF, version 2006) questionnaire to the Korean language and to evaluate its reliability and validity in a population of Korean patients with Behcet's disease (BD). METHODS: A cross cultural study was conducted among patients with BD who attended our rheumatology clinic between November 2012 and March 2013. There were 11 males and 35 females in the group. The mean age of the participants was 48.5 years and the mean disease duration was 6.4 years. The first BDCAF questionnaire was completed on arrival and the second assessment was performed 20 minutes later by a different physician. The test-retest reliability was analyzed by computing kappa statistics. Kappa scores of > 0.6 indicated a good agreement. To assess the validity, we compared the total BDCAF score with the patient's/clinician's perception of disease activity and the Korean version of the Behcet's Disease Quality of Life (BDQOL). RESULTS: For the test-retest reliability, good agreements were achieved on items such as headache, oral/genital ulceration, erythema, skin pustules, arthralgia, nausea/vomiting/abdominal pain, and diarrhea with altered/frank blood per rectum. Moderate agreement was observed for eye and nervous system involvement. We achieved a fair agreement for arthritis and major vessel involvement. Significant correlations were obtained between the total BDCAF score with the BDQOL and the patient's/clinician's perception of disease activity p < 0.05). CONCLUSIONS: The Korean version of the BDCAF is a reliable and valid instrument for measuring current disease activity in Korean BD patients. PMID- 26354068 TI - Type 4 dual left anterior descending coronary artery. PMID- 26354067 TI - Replication of the results of genome-wide and candidate gene association studies on telomere length in a Korean population. AB - BACKGROUND/AIMS: A number of genome-wide and candidate gene association studies have identified polymorphisms associated with telomere length in Caucasian populations. This study was conducted to determine the impacts of 17 polymorphisms identified in Caucasians on telomere length in a Korean population. METHODS: Ninety-four healthy individuals were enrolled in this study. Relative telomere length of chromosomes from peripheral blood samples was measured using quantitative polymerase chain reaction. RESULTS: Two polymorphisms, rs10936599 of MYNN and rs412658 of ZNF676, were found to be associated w ith telomere length (under dominant model, p = 0.04; under recessive model, p = 0.001). Three polymorphisms, rs2853669, rs7705526, and rs2736108, at the TERT locus were also associated with telomere length (under recessive model, p = 0.01, p = 0.02, and p = 0.01, respectively). The genotypes of the five polymorphisms associated with short telomere length were considered bad genotypes; telomere length was significantly decreased with increasing number of bad genotypes (p= 1.7 * 10( 5)). CONCLUSIONS: We have identified polymorphisms associated with telomere length in a Korean population. PMID- 26354069 TI - A novel PRKAR1A mutation resulting in a splicing variant in a case of Carney complex. PMID- 26354070 TI - Limited immune tolerance induced by transient mixed chimerism. PMID- 26354072 TI - Penicillin G-induced hemorrhagic cystitis. PMID- 26354071 TI - Complete recovery of pyoderma gangrenosum after successful treatment of underlying hairy cell leukemia with cladribine. PMID- 26354073 TI - Aortoduodenal syndrome: a rare cause of intestinal obstruction. PMID- 26354074 TI - Hepatic computed tomography changes caused by amiodarone. PMID- 26354075 TI - Rethinking the Relationship Between Academia and Industry: Qualitative Case Studies of MIT and Stanford. AB - As knowledge has become more closely tied to economic development, the interrelationship between academia and industry has become stronger. The result has been the emergence of what Slaughter and Leslie call academic capitalism. Inevitably, tensions between academia and industry arise; however, universities such as MIT and Stanford with long traditions of industry interaction have been able to achieve a balance between academic and market values. This paper describes the strategies adopted by MIT and Stanford to achieve this balance. The results indicate that implicit culture is a stronger determinant of balance than are explicit rules. Finally, the author proposes a concept of balance to reconsider the relationship between academia and industry: today's universities, particularly those with strengths in engineering and management, are both symbiotic and interdependent with industry. A reasonable attitude toward the university-industry relationship is that of balance rather than strict separation. Universities can thus establish effective mechanisms to reach a balance between conflicting values. PMID- 26354076 TI - Sensory modulation disorder symptoms in anorexia nervosa and bulimia nervosa: A pilot study. AB - OBJECTIVE: Individuals with anorexia nervosa (AN) and bulimia nervosa (BN) may exhibit reduced ability to modulate sensory, physiological, and affective responses. The aim of the present study is to assess sensory modulation disorder (SMD) symptoms in patients with AN and BN. METHOD: We assessed female adolescent and young adult inpatients with restrictive type anorexia nervosa (AN-R; n = 20) and BN (n = 20) evaluated in the acute stage of their illness, and 27 female controls. Another group of 20 inpatients with AN-R was assessed on admission and discharge, upon achieving their required weight. Participants completed standardized questionnaires assessing the severity of their eating disorder (ED) and the sensory responsiveness questionnaire (SRQ). RESULTS: Inpatients with AN-R demonstrated elevated overall sensory over-responsiveness as well as elevated scores on the taste/gustatory, vestibular/kinesthetic and somatosensory/tactile SRQ modalities compared with patients with BN and controls. Significant correlations between the severity of sensory over-responsiveness and ED-related symptomatology were found in acutely-ill patients with AN-R and to a lesser extent, following weight restoration. Elevated sensory over-responsiveness was retained in weight-restored inpatients with AN-R. Inpatients with BN demonstrated greater sensory under-responsiveness in the intensity subscale of the SRQ, but not in the frequency and combined SRQ dimensions. DISCUSSION: Female inpatients with AN-R exhibited sensory over-responsiveness both in the acute stage of their illness and following weight restoration, suggesting that sensory over responsiveness may represent a trait related to the illness itself above and beyond the influence of malnutrition. The finding for sensory under responsiveness in BN is less consistent. PMID- 26354077 TI - TERT promoter mutations in thyroid cancer: a report from a Middle Eastern population. AB - Telomerase reverse transcriptase (TERT) promoter mutations C228T and C250T have recently been described in follicular cell-derived thyroid cancer (TC) in patients from North America and Europe. In this study, we explored whether these findings could be replicated in patients from a different ethnic group. We screened 17 benign thyroid adenomas and 265 TC samples from patients in the Middle East for these mutations by PCR and direct sequencing using DNA isolated from paraffin-embedded tumor tissues. None of the 17 benign adenomas harbored TERT promoter mutations. Of 265 TC, 34 (12.8%) harbored TERT promoter mutations, including 10/153 (6.5%) conventional papillary TC (CPTC), 8/57 (14.0%) follicular variant PTC, 9/30 (30%) tall cell variant PTC, 1/3 (30%) Hurthle cell thyroid cancer (HTC), 1/5 (20%) follicular TC, and 5/13 (38.5%) poorly differentiated TC. C250T mutation was present in only 6/265 (2.3%) cases, while C228T mutation was present in a total of 28/265 (10.6%) cases. These two mutations were mutually exclusive. TERT promoter mutations were significantly more common in older (>=45 years) than younger patients and were associated with larger tumour size, vascular invasion, higher TNM stage (stage III and IV), BRAF(V600E) mutation and persistent/recurrent disease at 6-12 months after initial treatment and at the last follow up. These associations were stronger in non-CPTC. Thus, this study on a large cohort of TC patients from Middle East demonstrates that TERT promoter mutations are relatively common, especially in the non-CPTC, and are associated with more aggressive histopathological features, BRAF(V600E) mutation, and disease persistence/recurrence than the WT TERT. PMID- 26354078 TI - Titania may produce abiotic oxygen atmospheres on habitable exoplanets. AB - The search for habitable exoplanets in the Universe is actively ongoing in the field of astronomy. The biggest future milestone is to determine whether life exists on such habitable exoplanets. In that context, oxygen in the atmosphere has been considered strong evidence for the presence of photosynthetic organisms. In this paper, we show that a previously unconsidered photochemical mechanism by titanium (IV) oxide (titania) can produce abiotic oxygen from liquid water under near ultraviolet (NUV) lights on the surface of exoplanets. Titania works as a photocatalyst to dissociate liquid water in this process. This mechanism offers a different source of a possibility of abiotic oxygen in atmospheres of exoplanets from previously considered photodissociation of water vapor in upper atmospheres by extreme ultraviolet (XUV) light. Our order-of-magnitude estimation shows that possible amounts of oxygen produced by this abiotic mechanism can be comparable with or even more than that in the atmosphere of the current Earth, depending on the amount of active surface area for this mechanism. We conclude that titania may act as a potential source of false signs of life on habitable exoplanets. PMID- 26354081 TI - [Not Available]. PMID- 26354080 TI - Effect of delayed scanning on imaging and on the diagnostic accuracy of vertical root fractures in two photostimulable phosphor plates digital systems. AB - AIM: To evaluate the influence of delayed scanning on images obtained with two PSPs digital systems and on the diagnostic accuracy of vertical root fracture (VRF) by means of objective and subjective analyses. METHODOLOGY: Forty single rooted human teeth were divided into two groups, one without VRFs and another with VRFs induced by a universal testing machine. Two digital systems (VistaScan((r)) and Express((r)) ) were used to radiograph all teeth, and the resulting plates were scanned at four time-points: T0-immediately, T1-30 min, T2 2 h and T3-4 h after exposure. An aluminium (Al) wedge was used to evaluate the change in mean grey values as each scan was delayed. Three observers screened all images for VRFs, and one-fourth of the sample was revaluated after thirty days. Areas under the receiver operating characteristic (ROC) curve, sensitivity, specificity and accuracy values were compared by anova. RESULTS: Intra- and interobserver agreement ranged from moderate to substantial and fair to moderate, respectively. There was no significant difference amongst scan delays with regard to sensitivity, specificity and accuracy; however, there were significant differences in the area under the ROC curve, with the 4-h delayed scan being associated with lower values compared to the others (P = 0.019). As for objective analysis, there was a significant difference amongst all different scanning time points for the two systems (P = 0.001), except between the 30-min and 2-h delayed scans in the VistaScan((r)) system. CONCLUSION: Whilst delayed scanning caused changes to the density of images acquired with the systems studied, it did not seem to interfere with VRF diagnosis except when scanning was delayed for 4 h, which should therefore be avoided. PMID- 26354079 TI - Outbred genome sequencing and CRISPR/Cas9 gene editing in butterflies. AB - Butterflies are exceptionally diverse but their potential as an experimental system has been limited by the difficulty of deciphering heterozygous genomes and a lack of genetic manipulation technology. Here we use a hybrid assembly approach to construct high-quality reference genomes for Papilio xuthus (contig and scaffold N50: 492 kb, 3.4 Mb) and Papilio machaon (contig and scaffold N50: 81 kb, 1.15 Mb), highly heterozygous species that differ in host plant affiliations, and adult and larval colour patterns. Integrating comparative genomics and analyses of gene expression yields multiple insights into butterfly evolution, including potential roles of specific genes in recent diversification. To functionally test gene function, we develop an efficient (up to 92.5%) CRISPR/Cas9 gene editing method that yields obvious phenotypes with three genes, Abdominal-B, ebony and frizzled. Our results provide valuable genomic and technological resources for butterflies and unlock their potential as a genetic model system. PMID- 26354082 TI - Direct reciprocity in animals: The roles of bonding and affective processes. AB - The presence of direct reciprocity in animals is a debated topic, because, despite its evolutionary plausibility, it is believed to be uncommon. Some authors claim that stable reciprocal exchanges require sophisticated cognition which has acted as a constraint on its evolution across species. In contrast, a more recent trend of research has focused on the possibility that direct reciprocity occurs within long-term bonds and relies on simple as well as more complex affective mechanisms such as emotional book-keeping, rudimentary and higher forms of empathy, and inequity aversion, among others. First, we present evidence supporting the occurrence of long-term reciprocity in the context of existing bonds in social birds and mammals. Second, we discuss the evidence for affective responses which, modulated by bonding, may underlie altruistic behaviours in different species. We conclude that the mechanisms that may underlie reciprocal exchanges are diverse, and that some act in interaction with bonding processes. From simple associative learning in social contexts, through emotional contagion and behavioural mimicry, to empathy and a sense of fairness, widespread and diverse social affective mechanisms may explain why direct reciprocity may not be a rare phenomenon among social vertebrates. PMID- 26354083 TI - Kutzneria chonburiensis sp. nov., isolated from soil. AB - A novel actinomycete strain, SMC 256T, which developed small, globose sporangia at the ends of long sporangiophores on aerial mycelium, was isolated from soil collected in a mountain forest of Thailand. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain SMC 256T belonged to the genus Kutzneria, and the closest phylogenetically related species were Kutzneria buriramensis BCC 29373T (98.9 % 16S rRNA gene sequence similarity), Kutzneria kofuensis ATCC 27102T (98.2 %), Kutzneria albida ATCC 25243T (97.9 %) and Kutzneria viridogrisea ATCC 25242T (97.4 %). The DNA-DNA relatedness values that distinguished strain SMC 256T from previously described members of the genus Kutzneria were significantly below 70 %. The G+C content of the genomic DNA was 71.8 mol%. The cell-wall peptidoglycan contained meso-diaminopimelic acid. The whole-cell sugars consisted of rhamnose, ribose, mannose, glucose and galactose. The predominant menaquinone was MK-9(H4). Mycolic acids were not detected. The diagnostic phospholipids were hydroxyphosphatidylethanolamine, phosphatidylmethylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, phosphatidylinositol, phosphatidylinositol mannosides, unidentified phosphoglycolipids, unidentified phospholipids and an unidentified lipid. The predominant cellular fatty acids were iso-C16 : 0, C17 : 1 and C17 : 0 10-methyl. Following the evidence of phenotypic, chemotaxonomic and genotypic studies, it is proposed that strain SMC 256T represents a novel species in the genus Kutzneria, namely Kutzneria chonburiensis sp. nov. The type strain is SMC 256T ( = BCC 72675T = NBRC 110610T). PMID- 26354084 TI - Left Ventricular Assist Device Implantation in a Patient With Severe Cardiac Failure and Unilateral Pulmonary Agenesis. PMID- 26354085 TI - In vivo recruitment analysis and a mutant strain without any group 2 sigma factor reveal roles of different sigma factors in cyanobacteria. AB - In eubacteria, replacement of one sigma factor in the RNA polymerase (RNAP) holoenzyme by another one changes the transcription pattern. Cyanobacteria are eubacteria characterized by oxygenic photosynthesis, and they typically encode numerous group 2 sigma factors that closely resemble the essential primary sigma factor. A mutant strain of the model cyanobacterium Synechocystis sp. PCC 6803 without functional group 2 sigma factors (named as DeltasigBCDE) could not acclimate to heat, high salt or bright light stress, but in standard conditions DeltasigBCDE grew only 9% slower than the control strain. One-fifth of the genes in DeltasigBCDE was differently expressed compared with the control strain in standard growth conditions and several physiological changes in photosynthesis, and pigment and lipid compositions were detected. To directly analyze the sigma factor content of RNAP holoenzyme in vivo, a His-tag was added to the gamma subunit of RNAP in Synechocystis and RNAPs were collected. The results revealed that all group 2 sigma factors were recruited by RNAP in standard conditions, but recruitment of SigB and SigC increased in heat stress, SigD in bright light, SigE in darkness and SigB, SigC and SigE in high salt, explaining the poor acclimation of DeltasigBCDE to these stress conditions. PMID- 26354086 TI - Tabletting Process of Pellets Containing Bioactive Fraction DLBS1033F Isolated from Lumbricus rubellus: Challenge and Strategy. AB - DLBS1033 is a mixture of bioactive proteins fractinated from the earthworm Lumbricus rubellus which possesses antithrombotic and thrombolytic activities. DLBS1033 contains a potent fibrinolytic enzyme with excellent specificity for fibrin. A commercial oral enteric coated tablet for administration 3 times daily is available on the market from the DLBS manufacturer. This research aimed to develop a multiparticulate sustained-release DLBS1033 Forte (DLBS1033F) tablet (with more potent fibrinolytic activity than DLBS1033), which has targeted release in the small intestine and colon. The chemical and physical stability of the fibrinolytic enzyme was expected to be preserved in these bowel segments. The sustained-release system was designed to maintain the effective plasma concentration of the proteins and prolong the thrombolytic activity. This was done by incorporating the proteins in a multiparticulate solid that was subsequently compressed into the monolithic system of a sustained-release tablet. The challenge was to maintain pellet integrity after the compression process. A set of studies confirmed the preserved physical shape of the pellets. In addition, in vitro release studies of the multiparticulate tablet in reassembling media of the gastrointestinal tract indicated the successful formulation of DLBS1033F as an enteric as well as sustained-release solid dosage form. PMID- 26354087 TI - From student to graduate: longitudinal changes in the qualities of nurses. AB - AIMS: To examine the development of perceived qualities of nursing from student to graduate nurse over time. BACKGROUND: Researchers continue to explore student nurse and new graduate nurse attrition, particularly in the light of a looming crisis in nursing recruitment and retention. Qualities of nurses represent the job fit of nursing from student to graduate years. DESIGN: A prospective longitudinal design with a convenience sample was used for this study. METHODS: Data were collected annually from 2009-2012 through the completion of a short on line survey. The sample size of undergraduate nurses in year 1 was 676, with 527 in year 2, 339 in year 3 and 190 in year 4. Only 136 participants completed the survey each year forming the complete data set for analysis. RESULTS/FINDINGS: Most qualities of nursing differed significantly across time with the qualities of Caring, Empathetic, Knowledge and Respectful demonstrating strong changes. Most declines in scores occurred on graduation. Caring, the central tenet of nursing increased during the student years and declined slightly on graduation. CONCLUSION: This unique longitudinal study of Australian nurses suggests that the clinical experience and theoretical grounding provided in our University programs, has resulted in an increasing cumulative effect in the third year supporting most qualities of nurses/nursing understood in year 1, that is, the career fit to perceptions, has been achieved. The decline in the 1(st) year of graduation, where the concept of workplace misfit is occurring, is where further nurse graduate support is urgently required. PMID- 26354088 TI - A new standardized clinical-grade protocol for banking human umbilical cord tissue cells. AB - BACKGROUND: Mesenchymal stromal cells (MSCs) isolated from human umbilical cord tissue (UCT) can be considered the perfect candidates for cell-based therapies and regenerative medicine. UCT-derived MSCs can be cryogenically stored in cell banks and expanded as needed for therapeutic uses. STUDY DESIGN AND METHODS: We developed a new method for UCT-MSC isolation, cryopreservation, and expansion, following all criteria required by a stem cell bank. UCT-MSCs were isolated either by manual dissociation (MM) or by a semiautomatic dissociation system (SAM). In both protocols UCTs were treated enzymatically using Type IV collagenase good manufacturing practices (GMP) graded and hyaluronidase (medicinal product). Isolated UCT-MSCs were cryopreserved and analyzed after thawing for phenotype; for proliferation rate; and for their osteogenic, adipogenic, and chondrogenic differentiation capabilities. RESULTS: We found that SAM reduced the time of tissue enzyme exposure and enabled us to obtain a homogeneous single-cell suspension deprived of tissue fragments. The isolated cells in both groups showed high expression of MSC markers CD105, CD73, and CD90 and similar differentiation capabilities, phenotype, and proliferation potential. Moreover, the final yield of MSCs was comparable between the two techniques. CONCLUSION: In this study, we have established a reliable and standardized protocol to isolate UCT-MSCs from UCT for cell banking purposes. Processing the whole umbilical tissue with GMP-graded enzymes using a semiautomatic dissociator allowed us to obtain a single-cell suspension product with a known number of isolated cells that can be cryopreserved right after isolation and thawed as needed for expansion and clinical use. PMID- 26354089 TI - The anti-inflammatory activities of ethanol extract from Dan-Lou prescription in vivo and in vitro. AB - BACKGROUND: Although, Dan-Lou prescription (DLP) is used for antagonizing check discomfort and heartache, the pharmacological mechanism has not been clearly illustrated. Our present study aimed to design inflammatory models induced by LPS in vivo and in vitro to investigate the anti-inflammation of DLP ethanol extract (EEDL) and the potential mechanisms. METHODS: EEDL was prepared and then analyzed by high performance liquid chromatography (HPLC). Further, the anti-inflammatory effects of EEDL in vivo was evaluated by measuring inflammation-associated factors includingcytokines, chemokines and acute phase proteins in lipopolysaccharide (LPS)-induced mice serum and liver. The anti-inflammatory mechanism exploration of EEDL was performed in LPS-stimulated RAW 264.7 cells. Different effects of EEDL on nitric oxide (NO) and prostaglandin (PG)E2 secretion were investigated by Griess reagent method and enzyme-linked immunosorbent assay (ELISA) respectively. Then the mRNA and protein expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 were measured by real-time reverse transcription polymerase chain reaction (RT-PCR), ELISA and Western blot. Other chemokines and acute phase proteins were determined by proteome profile array. Finally, the ELISA based transcription factor assay was applied to measure the DNA-binding activity of nuclear transcription factor (NF)-kappaB p65. RESULTS: Eight compounds from EEDL have been identified as gallic acid, salvianic acid, puerarin, daidzin, paeoniflorin, salvianolic acid B, cryptotanshinone, and tanshinone IIA, with amounts of 0.26, 9.84, 10.41, 2.55, 9.44, 3.82, 0.24 and 0.3 mg/kg, respectively. In vivo, EEDL administration antagonized the up-regulation of more than 17 kinds of cytokines, chemokines and acute phase proteins in LPS treated mice serum, and inhibited LPS-induced IL-6 mRNA and protein expression in mice liver tissue. In vitro, LPS-induced NO and PGE2 over-productions were decreased by EEDL treatment. The mRNA and protein expression of iNOS, COX-2 and IL-6 were similarly inhibited by EEDL treatment, which might be attributed to decrease the DNA-binding activity of NF-kappaB p65. CONCLUSION: EEDL was valid for anti-inflammation and the potential molecular mechanisms might be due to the inhibition of of LPS-induced iNOS/NO, COX-2/PGE2 and cytokines expression by antagonizing the activation of NF-kappaB p65. PMID- 26354090 TI - Association of Clostridium difficile ribotype 078 with detectable toxin in human stool specimens. AB - Using a Clostridium difficile glutamate dehydrogenase (GDH) immunoassay and a sensitive C. difficile toxin A/B immunoassay, human stool specimens from patients with diarrhoea (n = 1085) were classified as either GDH positive/toxin negative, or GDH positive/toxin positive. Overall, 528/725 (73%) of the GDH-positive/toxin negative specimens contained viable C. difficile, and 433/528 (82%) of these C. difficile isolates were PCR positive for the toxin gene pathogenicity locus. Overall, 867/1078 (80%) of the GDH-positive specimens contained viable C. difficile, and 433/725 (60%) of the GDH-positive/toxin-negative specimens contained a toxigenic C. difficile strain. The diversity of toxigenic C. difficile ribotypes isolated from toxin-negative specimens (n = 433) and toxin positive specimens (n = 339) was significantly different (P < 0.0001). Specifically, the presence of ribotype 078 strains was very strongly associated (P < 0.0001) with detection of toxin in clinical specimens using a sensitive toxin immunoassay. Specimens positive for ribotype 078 were almost twice as likely to be toxin positive as opposed to toxin negative (risk ratio = 1.90, 95% confidence interval 1.64-2.19). In contrast, other circulating ribotypes were seen with similar frequency in specimens with and without detectable toxin. This supports the view that ribotype 078 strains may be more virulent than other common ribotypes in terms of toxin production. PMID- 26354091 TI - Interrelation of resting state functional connectivity, striatal GABA levels, and cognitive control processes. AB - Important issues for cognitive control are response selection processes, known to depend on fronto-striatal networks with recent evidence suggesting that striatal gamma-amino butyric acid (GABA) levels play an important role. Regional GABA concentrations have also been shown to modulate intrinsic connectivity, e.g. of the default mode network. However, the interrelation between striatal GABA levels, basal ganglia network (BGN) connectivity, and performance in cognitive control is elusive. In the current study, we measure striatal GABA levels using magnetic resonance spectroscopy (MRS) and resting state parameters using functional magnetic resonance imaging (fMRI). Resting state parameters include activity within the BGN, as determined by the low frequency power (LFP) within the network, and the functional connectivity between the BGN and somatomotor network (SMN). Specifically, we examine the interrelation between GABA, resting state parameters, and performance (i.e., accuracy) in conflict monitoring using a Simon task. Response control was affected by striatal GABA+ levels and activity within the BGN, especially when response selection was complicated by altered stimulus-response mappings. The data suggest that there are two mechanisms supporting response selection accuracy. One is related to resting state activity within the BGN and modulated by striatal GABA+ levels. The other is related to decreased cortico-striatal network connectivity, unrelated to the GABAergic system. The inclusion of all three factors (i.e., striatal GABA+ levels, activity within the BGN, and BGN-SMN network connectivity) explained a considerable amount of variance in task accuracy. Striatal neurobiochemical (GABA+) and parameters of the resting state BGN represent important modulators of response control. PMID- 26354092 TI - Comprehensive carrier genetic test using next-generation deoxyribonucleic acid sequencing in infertile couples wishing to conceive through assisted reproductive technology. AB - OBJECTIVE: To develop an expanded pan-ethnic preconception carrier genetic screening test for use in assisted reproductive technology (ART) patients and donors. DESIGN: Retrospective analysis of results obtained from 2,570 analyses. SETTING: Reproductive genetic laboratory. PATIENT(S): The 2,570 samples comprised 1,170 individuals from the gamete donor programs; 1,124 individuals corresponding to the partner of the patient receiving the donated gamete; and 276 individuals from 138 couples seeking ART using their own gametes. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Next-generation sequencing of 549 recessive and X-linked genes involved in severe childhood phenotypes reinforced with five complementary tests covering high prevalent mutations not detected by next-generation sequencing. RESULT(S): Preclinical validation included 48 DNA samples carrying known mutations for 27 genes, resulting in a sensitivity of 99%. In the clinical dataset, 2,161 samples (84%) tested positive, with an average carrier burden of 2.3 per sample. Five percent of the couples using their own gametes were found to have pathogenic variants conferring high risk for six different diseases. These high-risk couples and patients received genetic counseling and recommendations for preimplantation genetic diagnosis. For patients receiving gamete donation, we applied a genetic testing and blinded matching system to avoid high-risk combinations regardless of their carrier burden. For female donors, 1.94% were positive for X-linked conditions; they received genetic counselling and were discarded. CONCLUSION(S): We have developed a comprehensive carrier genetic screening test that, combined with our matching system and genetic counseling, constitutes a powerful tool to avoid more than 600 mendelian diseases in the offspring of patients undergoing ART. PMID- 26354093 TI - Prevention of the recurrence of symptom and lesions after conservative surgery for endometriosis. AB - Although surgical excision of endometriosis both improves pain and enhances fertility, recurrence can further exacerbate pain and reduce fertility, which in turn impacts the quality of life and increases personal as well as social costs. Therefore, it is crucial to prevent the recurrence of symptoms and lesions after conservative surgery. This article reviews evidence regarding the prevention of postoperative recurrence of endometriosis reported since the 1990s. Over the past 5 years, many new studies have been conducted and have demonstrated that long term postoperative medication markedly reduces the recurrence. Most of these studies used oral contraceptives (OC), with either the cyclic or continuous regimen, while some used oral or intrauterine progestin. Continuous OC is more efficacious than cyclic OC, especially for dysmenorrhea. The levonorgestrel releasing intrauterine system is also shown to prevent recurrence of dysmenorrhea and possibly endometriosis lesions. Dienogest, a new progestin, is shown to reduce the recurrence of endometrioma. Similar to the case of ovarian endometriosis, long-term postoperative medication after conservative surgery for deep infiltrating or extragenital endometriosis seems important, although data are limited. Regardless of the lesion and the medication type, patients who discontinued medication experienced a higher incidence of recurrence, indicating that the protective effect of these medications seems to vanish rapidly after the discontinuation. On the basis of these facts, together with the pathogenesis of recurrence (retrograde menstruation and ovulation), regular and prolonged medication until the patient wishes to conceive is highly recommended to prevent the postoperative recurrence of endometriosis. PMID- 26354095 TI - Clinical utility of magnetic resonance imaging and ultrasonography for diagnosis of polycystic ovary syndrome in adolescent girls. AB - OBJECTIVE: To evaluate ovarian morphology using three-dimensional magnetic resonance imaging (MRI) in adolescent girls with and without polycystic ovary syndrome (PCOS). Also compare the utility of MRI versus ultrasonography (US) for diagnosis of PCOS. DESIGN: Cross-sectional study. SETTING: Urban academic tertiary-care children's hospital. PATIENT(S): Thirty-nine adolescent girls with untreated PCOS and 22 age/body mass index (BMI)-matched controls. INTERVENTION(S): Magnetic resonance imaging and/or transvaginal/transabdominal US. MAIN OUTCOME MEASURE(S): Ovarian volume (OV); follicle number per section (FNPS); correlation between OV on MRI and US; proportion of subjects with features of polycystic ovaries (PCOs) on MRI and US. RESULT(S): Magnetic resonance imaging demonstrated larger OV and higher FNPS in subjects with PCOS compared with controls. Within the PCOS group, median OV was 11.9 (7.7) cm(3) by MRI compared with 8.8 (7.8) cm(3) by US. Correlation coefficient between OV by MRI and US was 0.701. Due to poor resolution, FNPS could not be determined by US or compared with MRI. The receiver operating characteristic curve analysis for MRI demonstrated that increasing volume cutoffs for PCOs from 10-14 cm(3) increased specificity from 77%-95%. For FNPS on MRI, specificity increased from 82%-98% by increasing cutoffs from >= 12 to >= 17. Using Rotterdam cutoffs, 91% of subjects with PCOS met PCO criteria on MRI, whereas only 52% met criteria by US. CONCLUSION(S): Ultrasonography measures smaller OV than MRI, cannot accurately detect follicle number, and is a poor imaging modality for characterizing PCOs in adolescents with suspected PCOS. For adolescents in whom diagnosis of PCOS remains uncertain after clinical and laboratory evaluation, MRI should be considered as a diagnostic imaging modality. PMID- 26354094 TI - Predictors of participant retention in infertility treatment trials. AB - OBJECTIVE: To identify variables associated with retention (or dropout) in infertility clinical trials. Retention of subjects in randomized controlled clinical trials (RCTs) has received considerable attention, but there have been few consistent findings. DESIGN: Secondary analysis of data from RCTs. SETTING: Academic medical centers. PATIENT(S): Women with polycystic ovary syndrome (PCOS) or couples with unexplained infertility, aged 18-40 years. INTERVENTION(S): This study is not an intervention study, but the patients in the original RCTs were treated with any or combination of metformin, clomiphene citrate (CC), letrozole, and gonadotropins. MAIN OUTCOME MEASURE(S): Successful retention versus dropout during the RCTs. RESULT(S): Race, ethnicity, body mass index (BMI), insurance coverage, history of smoking, and history of alcohol use were significantly associated with retention whether they were considered in bivariate analyses or a multivariable logistic model. Specifically, white race, higher income, having graduate degrees, normal weight, better insurance coverage, nonsmokers, and those who reported current use of alcohol at the start of the trial, had higher retention rates. CONCLUSION(S): We identified several additive and persistent predictors of retention that can be used to guide the conduct of RCTs and improve the retention rate. Given the limitation of our association analysis, methodologically sound and theoretically grounded research are warranted so that high quality data can be collected to improve our understanding on the causes of dropout. CLINICAL TRIAL REGISTRATION NUMBER: NCT00068861 (PPCOS-I), NCT00719186 (PPCOS-II), and NCT01044862 (AMIGOS). PMID- 26354096 TI - Analysis of the correlation of CATSPER single nucleotide polymorphisms (SNPs) with idiopathic asthenospermia. AB - PURPOSE: Idiopathic asthenospermia is the most common type of male infertility. Although the mechanisms causing asthenospermia are complex, recent studies have indicated an important role of cation channel of sperm (CATSPER) gene downregulation or abnormality in the etiology of idiopathic asthenospermia. METHODS: In the present study, 192 patients with idiopathic asthenospermia and 288 healthy controls were enrolled, and a flight mass spectrometry using Sequenom's MassArray biochip system was applied for genotyping 16 CATSPER gene SNPs reported in the human single nucleotide polymorphism (SNP) database. RESULTS: Our results indicated a correlation between CATSPER1 SNPs and idiopathic asthenospermia. In particular, the exonal SNP rs1893316 in CATSPER1 significantly correlated with idiopathic asthenospermia risk and is a potential important factor in determining an individual's genetic susceptibility to idiopathic asthenospermia. CONCLUSION: These finding will help to further elucidate the role of CATSPER1 in idiopathic asthenospermia pathogenesis. PMID- 26354098 TI - From the Au nano-clusters to the nanoparticles on 4H-SiC (0001). AB - The control over the configuration, size, and density of Au nanoparticles (NPs) has offered a promising route to control the spatial confinement of electrons and photons, as a result, Au NPs with a various configuration, size and density are witnessed in numerous applications. In this work, we investigate the evolution of self-assembled Au nanostructures on 4H-SiC (0001) by the systematic variation of annealing temperature (AT) with several deposition amount (DA). With the relatively high DAs (8 and 15 nm), depending on the AT variation, the surface morphology drastically evolve in two distinctive phases, i.e. (I) irregular nano mounds and (II) hexagonal nano-crystals. The thermal energy activates adatoms to aggregate resulting in the formation of self-assembled irregular Au nano-mounds based on diffusion limited agglomeration at comparatively low annealing temperature, which is also accompanied with the formations of hillocks and granules due to the dewetting of Au films and surface reordering. At high temperature, hexagonal Au nano-crystals form with facets along {111} and {100} likely due to anisotropic distribution of surface energy induced by the increased volume of NPs. With the small DA (3 nm), only dome shaped Au NPs are fabricated along with the variation of AT from low to elevated temperature. PMID- 26354099 TI - A case series and review of Poncet's disease, and the utility of current diagnostic criteria. AB - AIM: Poncet's disease is a well recognized form of reactive arthritis in the presence of extra-articular tuberculosis. There are very limited case reports even from countries where tuberculosis is common and there are no accepted diagnostic criteria for Poncet's disease. In the present study we are describing clinical features of Poncet's disease from a tuberculosis-endemic region along with a proposal of a new diagnostic criteria. METHODS: All patients diagnosed as having Poncet's disease were included. The clinical details, demographic features, pattern of joint involvement, investigation findings, treatment details and clinical outcomes were recorded on a structured pro forma. RESULTS: Twenty three patients with Poncet's disease were identified during the study period. Thirteen patients had oligoarthritis and the rest had polyarthritis with ankle joint involvement being most common. The duration of joint symptoms varied from 3 days to 6 years. All patients had non-erosive and non-deforming arthritis. Systemic symptoms were absent in 48% of patients. Mantoux was positive in most cases (81%). Tuberculosis was extrapulmonary in most cases, lymph node tuberculosis being most common. All patients had complete resolution of joint symptoms with anti-tubercular treatment. All the factors contributing to eventual diagnosis of Poncet's disease were carefully analyzed and diagnostic criteria are proposed. In the proposed criteria, there are two essential, two major and three minor criteria. According to these criteria 19 patients had definite and three had probable Poncet's disease. CONCLUSION: The most common presentation of Poncet's is in the form of oligoarthritis. The proposed criteria can be used for diagnosing Poncet's disease. PMID- 26354100 TI - Fatty acid and vitamin interventions in adults with schizophrenia: a systematic review of the current evidence. AB - Current psychopharmacological approaches to reduce psychotic phenomenology in schizophrenia are associated with adverse effects including extrapyramidal and metabolic side effects. In view of the emerging data on nutritional supplementation interventions in schizophrenia which are not entirely consistent, we aimed to review existent studies focusing on fatty acid and vitamin interventions and summarise current evidence on such nutritional supplementations in schizophrenia. We searched the digital databases (ScienceDirect, Scopus, SpringerLINK, PubMed/Medline) for relevant studies pertaining to fatty acid and vitamin supplementation interventions in the management of psychotic symptoms in schizophrenia up to February 2015. Overall, there were more studies conducted on fatty acid over vitamin supplementations in patients with schizophrenia. There were more positive findings in support of fatty acid supplementation compared with vitamin supplementation in the context of specific intervention features (dose of nutrient supplementation, single versus combination nutritional interventions, specific antipsychotic), subject features (older age, long duration of illness, baseline polyunsaturated fatty acid levels) and clinical outcomes (improvements of psychotic symptoms and/or extrapyramidal side effects from antipsychotics). However, investigations of both supplementation modalities were limited by relatively small study sample sizes, short study duration, which precluded further segmentation of impact on more diverse patient subtypes and symptom profiles. Future studies may consider examining larger samples over a longer time period, recruiting younger subjects with shorter duration of illness, examination of different clinical features including specific cognitive domains, and use of single versus combination nutritional interventions. PMID- 26354101 TI - A genetic variant in CAMKK2 gene is possibly associated with increased risk of bipolar disorder. AB - A recent large-scale study have reported that rs1063843, a single nucleotide polymorphism located in the CAMKK2 gene is highly associated with schizophrenia in European and Han Chinese populations. Increasing evidences show that schizophrenia and bipolar disorder have some common genetic variance. Here, we evaluated the association of this variant with schizophrenia and bipolar disorder in Iranian population. Genomic DNA was extracted from peripheral blood of 500 schizophrenic patients, 500 bipolar patients and 500 normal controls and all were genotyped for the rs1063843 using a PCR-RFLP method. The allele frequency of rs1063843 was significantly different in both schizophrenia and bipolar patients comparing to control group. For the first time, we showed that rs1063843 is highly associated with bipolar disorder, although more replication studies are needed to confirm our findings. Our results also support the findings of previous studies suggesting a significant association between rs1063843 and schizophrenia. PMID- 26354102 TI - Generalized motor inhibitory deficit in Parkinson's disease patients who freeze. AB - Freezing of gait is a disabling symptom of Parkinson's disease (PD) that involves failure to initiate and continue motor activity appropriately. PD disrupts fronto basal ganglia circuitries that also implement the inhibition of responses, leading to the hypothesis that freezing of gait may involve fundamental changes in both initiation and inhibition of motor actions. We asked whether PD patients who show freezing of gait show selective deficits in their ability to inhibit upper and lower extremity reactions. We compared older healthy controls, older PD controls without freezing of gait, and older PD participants with freezing of gait, in stop-signal tasks that measured the initiation (go trials) and inhibition (stop trials) of both hand and foot responses. When only go trials were presented, all three groups showed similar initiation speeds across lower and upper extremity responses. When stop-signal trials were introduced, both PD groups slowed their reactions nearly twice as much as healthy controls. While this adjustment helped PD controls stop their actions as quickly as healthy controls, PD patients with freezing showed significantly delayed inhibitory control of both upper and lower extremities. When anticipating the need to stop their actions urgently, PD patients show greater adjustments (i.e., slowing) to reaction speed than healthy controls. Despite these proactive adjustments, PD patients who freeze show marked impairments in inhibiting both upper and lower extremity responses, suggesting that freezing may involve a fundamental disruption to the brain's inhibitory control system. PMID- 26354103 TI - Health status, anxiety, and depressive symptoms following complicated and uncomplicated colorectal surgeries. AB - PURPOSE: The purpose of this study was to evaluate the impact of complications following colorectal surgery on anxiety, depressive symptoms, and health status. Previously, very few studies examined the psychological impact of complications following colorectal surgery. Also, in clinical practice, little attention is paid to the psychological impact of complications. METHODS: Patients undergoing colorectal surgery were evaluated prospectively preoperatively and postoperatively at 3 days, 6 weeks, and 1 year, using the Center for Epidemiological Studies-Depression (CES-D), State-Trait Anxiety Inventory (STAI), and Short Form 36 (SF-36) questionnaires. Patient data and complications were prospectively recorded. Postoperative CES-D, STAI, and SF-36 scores in patients with minor and severe complications were compared to scores of patients without complications using a general linear model. RESULTS: Of 218 patients, 130 (59.6%) had complications. Colorectal surgery significantly increased depressive symptoms and anxiety levels in the same amount in all patient subgroups. Furthermore, it also lowered all domains of health status in all patient subgroups, but not equally. Patients with a severely complicated postoperative course had a larger postoperative decrease in health status, most notably at 6 weeks postoperatively with the largest effects in the physical-, mental-, social-, and vitality domains compared with the other subgroups. CONCLUSIONS: Colorectal surgery has a profound effect on depressive and anxiety symptoms, as well as nearly all domains of health status. Occurrence of severe complications increases the negative effect of colorectal surgery on most domains of health status but do not specifically increase depressive symptoms or anxiety levels. At 6 weeks, these effects are most notable, but at 1 year, they have faded. PMID- 26354104 TI - Multi-level surgery for obstructive sleep apnea. Lingual tonsillectomy vs. hyoid suspension in combination with radiofrequency of the tongue base. AB - PURPOSE: The aim of this study was to compare results in patients with obstructive sleep apnea (OSA) undergoing multi-level surgery with two different surgical approaches to treat tongue base obstruction. STUDY DESIGN: This is a prospective, controlled clinical trial at a tertiary referral center. METHODS: Altogether, 108 patients were separated into two groups according to the findings during drug-induced sleep endoscopy. Patients with enlarged lingual tonsils (N = 58; group A) underwent a lingual tonsillectomy (LT). Patients with small or absent lingual tonsils (N = 50; group B) underwent a hyoid suspension type 2 (HS) in combination with a radiofrequency treatment of the base of the tongue (RFT TB). In addition, all patients underwent an uvulopalatopharyngoplasty with tonsillectomy. RESULTS: At baseline, there were no significant differences between the groups. In group A, the mean apnea hypopnea index (AHI) decreased by 49.7 %, and in group B by 48.3 %. Patients with simultaneous tonsillectomies showed significant better results as compared to patients after prior tonsillectomies (success rate 76.6 vs. 27.3 %). By comparing subgroups (with and without simultaneous tonsillectomy), patients in group A showed better results in terms of AHI reduction than patients in group B, indicating that LT may be superior to HS + RFT TB in treating OSA within our multi-level surgery concept. CONCLUSION: Simultaneous tonsillectomy has a significant impact on objective results of multi-level surgery (MLS). Study results should be adjusted for this parameter. Having done this, MLS with LT seems to produce superior results as compared to HS + RFT TB. Nevertheless, our approach to treat patients differently according to their tongue base tonsil size did not substantially improve our surgical outcome as compared to a previous study. PMID- 26354105 TI - High-resolution wrist-worn overnight oximetry has high positive predictive value for obstructive sleep apnea in a sleep study referral population. AB - BACKGROUND: Reducing the need for diagnostic sleep studies for obstructive sleep apnea (OSA) would reduce direct and opportunity costs while expediting time to treatment for this common and morbid disorder. We sought to determine if an established sleep apnea screening questionnaire (STOP-BANG) and wrist-worn overnight oximetry data could provide high positive predictive value for the presence of OSA. METHODS: We conducted a prospective observational study of consecutive unattended sleep study patients at a single facility. Patients were referred for sleep testing after chart review by a sleep physician. We assessed area under the receiver-operating characteristic curve (ROC AUC) and positive predictive value (PPV) of STOP-BANG score and oxygen desaturation index (ODI) for a respiratory disturbance index (RDI) >=15/h. RESULTS: Among 234 test patients, 65 % had an RDI >=15/h. STOP-BANG had poor ability to discriminate these patients (ROC AUC 0.62). ODI added significant diagnostic information to the STOP-BANG score, increasing the ROC AUC to 0.86. Having the ODI, the STOP-BANG score no longer contributed significant diagnostic information, and the ODI alone discriminated as well as the combination (ROC AUC 0.86). Forty nine percent had an ODI >=7/h, which had PPV of 92 % (95 % confidence interval (CI), 86 to 96 %). In the validation sample of 1,196 consecutive patients, ODI >= 7/h had a PPV of 97 % (95 % CI, 95 to 97 %). CONCLUSIONS: Among patients with a high prevalence of OSA, high ODI is common and its presence has high PPV for OSA. These data suggest that overnight oximetry prior to sleep testing could significantly reduce the number of patients requiring sleep studies, thereby reducing costs and time to treatment. PMID- 26354106 TI - Association between sleep quality and inflammatory complement components in collegiate males. AB - BACKGROUND: An accumulating amount of evidence has linked humoral mediators of inflammation with sleep measures. Nevertheless, important details of this association, in particular the role of the complement components in the context of chronic sleep attributes, have remained largely uncharacterized. MATERIALS AND METHODS: Fifty university students (age, 23.3 +/- 3.8 years; BMI, 23.7 +/- 2.9 kg/m(2)) completed the study. Four dichotomized sleep measures assessed by the Pittsburgh Sleep Quality Index (PSQI) were used in association analysis using binary logistic regression with complement component 3, 4, and complement factor I (CFI). The sleep measures were defined as sleep quality (good sleep/poor sleep; PSQI <=5/PSQI >5), bedtime (early/late; before 00:00 h/after 0:00 h), sleep duration (short/normal <=6 h/>6 h), and sleep onset latency (normal/disturbed; 0 1 score/2-3 score on the PSQI component of sleep latency). RESULTS: The complement component 4 was associated with sleep quality (unadjusted, OR = 1.025, p < 0.05; adjusted for age, OR = 1.025, p < 0.05; adjusted for BMI, OR = 1.027, p < 0.05) and sleep duration (unadjusted, OR = 1.041, p < 0.01; adjusted for age, OR = 1.041, p < 0.01; adjusted for BMI, OR = 1.046, p < 0.01). CFI was associated with bedtime (unadjusted, OR = 0.737, p < 0.01; adjusted for age, OR = 0.717, p < 0.01; adjusted for BMI, OR = 0.677, p < 0.01) and with sleep duration (unadjusted, OR = 0.796, p < 0.05; adjusted for age, OR = 0.796, p < 0.05). CONCLUSION: The findings indicate the importance of the role of complement components in the dynamics of sleep. Therefore, sleep should be assessed in conditions where complement components are affected. PMID- 26354107 TI - Increased MCP-1 gene expression in monocytes of severe OSA patients and under intermittent hypoxia. AB - PURPOSE: Obstructive sleep apnea (OSA) is known to be a risk factor of coronary artery disease. Monocyte chemoattractant protein-1 (MCP-1), as a critical factor for monocyte infiltration, is known to play a role in the development of atherosclerosis. This study aimed to investigate the effect of intermittent hypoxia, the hallmark of OSA, on the MCP-1 expression of monocytes. METHODS: Peripheral blood was sampled from 61 adults enrolled for suspected OSA. RNA was prepared from the isolated monocytes for the analysis of MCP-1. The effect of in vitro intermittent hypoxia on the regulation and function of MCP-1 was investigated on THP-1 monocytic cells and human monocytes. The mRNA and secreted protein levels were investigated by RT/real-time PCR and enzyme-linked immunosorbent assay, respectively. RESULTS: Monocytic MCP-1 gene expression was found to be increased significantly in severe OSA patients. In vitro intermittent hypoxia was demonstrated to increase the mRNA and protein expression levels of MCP-1 dose- and time-dependently in THP-1 monocytic cells. The MCP-1 mRNA expression in monocytes isolated from OSA patient was induced to a much higher level compared to that from normal control. Pre-treatment with inhibitor for p42/44 MAPK or p38 MAPK suppressed the activation of MCP-1 expression by intermittent hypoxia. CONCLUSIONS: This is the first study to demonstrate the increase of MCP-1 gene expression in monocytes of severe OSA patients. In addition, monocytic MCP-1 gene expression can be induced under intermittent hypoxia. PMID- 26354108 TI - Erratum to: Neuroprotective effect of Spirulina fusiform and amantadine in the 6 OHDA induced Parkinsonism in rats. PMID- 26354109 TI - Solution structure of human MBD1 CXXC1. PMID- 26354111 TI - Modulatory role of mineral nutrients on cadmium accumulation and stress tolerance in Oryza sativa L. seedlings. AB - Cadmium (Cd)-contaminated rice is a serious health concern. In the present study, Cd accumulation and stress responses in Oryza sativa L. cv MTU 7029 seedlings were characterized under varying concentrations of plant nutrients in Hoagland media. It has been found that nutrient supplement modulates Cd accumulation and related stress tolerance while efficacy of each nutrient varies. Supplementation of Fe, Mn, N, Ca, and S were found to reduce Cd accumulation in leaf whereas Mn and Fe supply effect was also observed in roots. Analysis of maximum quantum efficiency of photosynthesis indicated that Fe and S supplements confer highest Cd stress tolerance. The present study highlighted the potential of plant nutrients for minimizing Cd accumulation and its toxicity in rice seedlings. PMID- 26354110 TI - Evaluation of coexposure to inorganic arsenic and titanium dioxide nanoparticles in the marine shrimp Litopenaeus vannamei. AB - The acute toxicity of titanium dioxide nanoparticles (nTiO2) that occur concomitantly in the aquatic environment with other contaminants such as arsenic (As) is little known in crustaceans. The objective of the present study is to evaluate whether coexposure to nTiO2 can influence the accumulation, metabolism, and oxidative stress parameters induced by arsenic exposure in the gills and hepatopancreas of the shrimp Litopenaeus vannamei. Organisms were exposed by dissolving chemicals in seawater (salinity = 30) at nominal concentrations of 10 MUg/L nTiO2 or As(III), dosed alone and in combination. Results showed that there was not a significant accumulation of As in either tissue type, but the coexposure altered the pattern of the metabolism. In the hepatopancreas, no changes were observed in the biochemical response, while in the gills, an increase in the glutamate-cysteine-ligase (GCL) activity was observed upon exposure to As or nTiO2 alone, an increase in the reduced glutathione (GSH) levels was observed upon exposure to As alone, and an increase in the total antioxidant capacity was observed upon exposure to nTiO2 or nTiO2 + As. However, these modulations were not sufficient enough to prevent the lipid damage induced by nTiO2 exposure. Our results suggest that coexposure to nTiO2 and As does not alter the toxicity of this metalloid in the gills and hepatopancreas of L. vannamei but does alter its metabolism, favoring its accumulation of organic As species considered moderately toxic. PMID- 26354113 TI - Catalytic hydrothermal treatment of pulping effluent using a mixture of Cu and Mn metals supported on activated carbon as catalyst. AB - The present study was performed to investigate the performance of activated carbon-supported copper and manganese base catalyst for catalytic wet oxidation (CWO) of pulping effluent. CWO reaction was performed in a high pressure reactor (capacity = 0.7 l) at temperatures ranging from 120 to 190 degrees C and oxygen partial pressures of 0.5 to 0.9 MPa with the catalyst concentration of 3 g/l for 3 h duration. With Cu/Mn/AC catalyst at 190 degrees C temperature and 0.9 MPa oxygen partial pressures, the maximum chemical oxygen demand (COD), total organic carbon (TOC), lignin, and color removals of 73, 71, 86, and 85 %, respectively, were achieved compared to only 52, 51, 53, and 54 % removals during the non catalytic process. Biodegradability (in terms of 5-day biochemical oxygen demand (BOD5) to COD ratio) of the pulping effluent was improved to 0.38 from an initial value of 0.16 after the catalytic reaction. The adsorbed carbonaceous fraction on the used catalyst was also determined which contributed meager TOC reduction of 3 4 %. The leaching test showed dissolution of the metals (i.e., Cu and Mn) from the catalysts in the wastewater during CWO reaction at 190 degrees C temperature and 0.9 MPa oxygen partial pressures. In the future, the investigations should focus on the catalyst reusability. PMID- 26354114 TI - A comparison of risk modeling tools and a case study for human health risk assessment of volatile organic compounds in contaminated groundwater. AB - In order to promote the risk-based strategy in the investigation, assessment, and remediation of Chinese brownfield sites, the Health and Environmental Risk Assessment (HERA) software was developed. It is vital to validate the HERA model and compare the inter-model differences of HERA model against other available risk assessment tools. This paper discusses the similarities and differences between the Risk-Based Corrective Action (RBCA) Tool Kit and the HERA model by evaluating the health risk of organic contaminated groundwater sources for a chemical works in China for the first time. Consequently, the HERA and RBCA models yielded the identical results for Site-Specific Assessment Criteria (SSAC) under the commercial redevelopment. However, the HERA estimated more conservative and stringent SSACs under the residential scenario based on the different exposure calculations. The inhalation of indoor vapors was the most predominated exposure pathway for all the volatile organic compounds (VOCs) determined using the RBCA and HERA models. According to the HERA model, inhalation of chloroform may cause the highest unacceptable carcinogenic risk at 2.31 * 10(-3) under the residential scenario. Therefore, it is recommended that a risk-based remedial strategy be developed to ensure the safe and sustainable redevelopment of the site. PMID- 26354112 TI - Bioaccumulation and molecular effects of sediment-bound metals in zebrafish embryos. AB - Predicting the bioavailability and effects of metals in sediments is of major concern in context with sediment risk assessment. This study aimed to investigate the bioavailability and molecular effects of metals spiked into riverine sediments to zebrafish (Danio rerio) embryos. Embryos were exposed to a natural and an artificial sediment spiked with cadmium (Cd), copper (Cu), nickel (Ni) and zinc (Zn) individually or as a mixture at concentrations ranging from 150 to 3000 mg/kg dry weight (dw) over 48 h, and uptake of metals was determined. Furthermore, transcript abundances of the metallothioneins MT1 and MT2, the metal responsive element-binding transcription factor (MTF) and the genes sod1, hsp70 and hsp90alpha1 were measured as indicators of metal-induced or general cellular stress. D. rerio embryos accumulated metals from sediments at concentrations up to 100 times greater than those spiked to the sediment with the greatest bioaccumulation factor (BAF) for Cu from artificial sediment (275.4 +/- 41.9 (SD)). Embryos accumulated greater concentrations of all metals from artificial than from natural sediment, and accumulation was greater when embryos were exposed to individual metals than when they were exposed to the mixture. Exposure of embryos to Zn or the mixture exhibited up to 30-fold greater transcript abundances of MT1, MT2 and hsp70 compared to controls which is related to significant uptake of Zn from the sediment. Further changes in transcript abundances could not be related to a significant uptake of metals from sediments. These studies reveal that metals from spiked sediments are bioavailable to D. rerio embryos directly exposed to sediments and that the induction of specific genes can be used as biomarkers for the exposure of early life stages of zebrafish to metal-contaminated sediments. PMID- 26354115 TI - Power generation by high head water in a building using micro hydro turbine-a greener approach. AB - Demand for green energy production is arising all over the world. A lot of emphasis is laid in making the buildings green. Even a small amount of energy savings made contribute to saving the environment. In this study, an idea is proposed and studied to extract power from the high head water in the pipelines of a building. A building of height 15 m is considered for this study. Water flowing in the pipe has sufficient energy to run a micro hydro turbine. The feasibility of producing electrical energy from the energy of pipe water is found. The motivation is to find the feasibility of generating power using a low cost turbine. The experimental setup consists of micro turbine of 135 mm diameter coupled to a 12-V DC generator; LEDs and resistors are employed to validate the results. The theoretical calculations were presented using the fundamental equations of fluid mechanics. The theoretical results are validated using experimental and numerical results using CFD simulation. In addition, exergy analysis has been carried out to quantify the irreversibilities during the process in the system. PMID- 26354116 TI - Saudi dental students' perceptions of pediatric behavior guidance techniques. AB - BACKGROUND: Dental students receive theoretical and clinical training in pediatric behavioral guidance techniques at university. Therefore, the content of the educational course and the degree of training in behavioral techniques may have an impact on the students' perceptions and practice of such techniques. The purpose of this study was to evaluate Saudi dental students' perceptions of behavior guidance techniques used in pediatric dentistry, and to assess the changes in their perceptions after 1 academic year of a didactic and clinical educational course. METHODS: This longitudinal study was carried out once at the beginning and once at the end of the 2013/2014 academic year at the College of Dentistry, King Saud University in Riyadh, Saudi Arabia. A questionnaire measuring the perceived acceptability of behavior guidance techniques was completed by 78 fourth-year dental students before and after a pediatric dental course. Acceptability ratings were scored on a 5-point Likert scale and compared and evaluated in relation to demographic data. Paired t-test and one-way analysis of variance were used for the statistical analyses. RESULTS: Before the course, the highest scores were for reinforcement and desensitizing techniques and the lowest were for aversive and communicative techniques. After the course, statistically significant increases were found in the acceptability of aversive techniques (voice control and hand-over-mouth), all pharmacological techniques, and modeling. Most communicative techniques and clinical situations were also rated as significantly more acceptable. Statistically significant decreases in acceptability ratings were found in promising a toy, and immobilization by staff or a parent. Immobilization using a papoose board, modeling, the presence of parents during the child's treatment, and most communicative techniques were rated as significantly more acceptable by male students than female students. CONCLUSIONS: In general, Saudi dental students rated most basic behavior guidance techniques as acceptable. An educational course, including didactic and clinical components, improved their acceptability ratings, and had a considerable influence on their perceptions of behavior guidance in pediatric dentistry. PMID- 26354117 TI - Bioimaging: An Useful Tool to Monitor Differentiation of Human Embryonic Stem Cells into Chondrocytes. AB - To improve the recovery of damaged cartilage tissue, pluripotent stem cell-based therapies are being intensively explored. A number of techniques exist that enable monitoring of stem cell differentiation, including immunofluorescence staining. This simple and fast method enables changes to be observed during the differentiation process. Here, two protocols for the differentiation of human embryonic stem cells into chondrocytes were used (monolayer cell culture and embryoid body formation). Cells were labeled for markers expressed during the differentiation process at different time points (pluripotent: NANOG, SOX2, OCT3/4, E-cadherin; prochondrogenic: SOX6, SOX9, Collagen type II; extracellular matrix components: chondroitin sulfate, heparan sulfate; beta-catenin, CXCR4, and Brachyury). Comparison of the signal intensity of differentiated cells to control cell populations (articular cartilage chondrocytes and human embryonic stem cells) showed decreased signal intensities of pluripotent markers, E-cadherin and beta-catenin. Increased signal intensities of prochondrogenic markers and extracellular matrix components were observed. The changes during chondrogenic differentiation monitored by evaluation of pluripotent and chondrogenic markers signal intensity were described. The changes were similar to several studies over chondrogenesis. These results were confirmed by semi-quantitative analysis of IF signals. In this research we indicate a bioimaging as a useful tool to monitor and semi-quantify the IF pictures during the differentiation of hES into chondrocyte-like. PMID- 26354119 TI - Factors affecting professional ethics in nursing practice in Iran: a qualitative study. AB - BACKGROUND: Professional ethics refers to the use of logical and consistent communication, knowledge, clinical skills, emotions and values in nursing practice. This study aimed to explore and describe factors that affect professional ethics in nursing practice in Iran. METHODS: This qualitative study was conducted using conventional content analysis approach. Thirty nurses with at least 5 years of experience participated in the study; they were selected using purposive sampling. Data were collected through semi-structured interviews and analyzed using thematic analysis. RESULTS: After encoding and classifying the data, five major categories were identified: individual character and responsibility, communication challenges, organizational preconditions, support systems, educational and cultural development. CONCLUSIONS: Awareness of professional ethics and its contributing factors could help nurses and healthcare professionals provide better services for patients. At the same time, such understanding would be valuable for educational administrators for effective planning and management. PMID- 26354120 TI - Miraculous Survival of a Patient With Pheochromocytoma and Takotsubo Syndrome. PMID- 26354118 TI - Computational Modeling for Enhancing Soft Tissue Image Guided Surgery: An Application in Neurosurgery. AB - With the recent advances in computing, the opportunities to translate computational models to more integrated roles in patient treatment are expanding at an exciting rate. One area of considerable development has been directed towards correcting soft tissue deformation within image guided neurosurgery applications. This review captures the efforts that have been undertaken towards enhancing neuronavigation by the integration of soft tissue biomechanical models, imaging and sensing technologies, and algorithmic developments. In addition, the review speaks to the evolving role of modeling frameworks within surgery and concludes with some future directions beyond neurosurgical applications. PMID- 26354121 TI - Akt1/protein kinase B enhances transcriptional reprogramming of fibroblasts to functional cardiomyocytes. AB - Conversion of fibroblasts to functional cardiomyocytes represents a potential approach for restoring cardiac function after myocardial injury, but the technique thus far has been slow and inefficient. To improve the efficiency of reprogramming fibroblasts to cardiac-like myocytes (iCMs) by cardiac transcription factors [Gata4, Hand2, Mef2c, and Tbx5 (GHMT)], we screened 192 protein kinases and discovered that Akt/protein kinase B dramatically accelerates and amplifies this process in three different types of fibroblasts (mouse embryo, adult cardiac, and tail tip). Approximately 50% of reprogrammed mouse embryo fibroblasts displayed spontaneous beating after 3 wk of induction by Akt plus GHMT. Furthermore, addition of Akt1 to GHMT evoked a more mature cardiac phenotype for iCMs, as seen by enhanced polynucleation, cellular hypertrophy, gene expression, and metabolic reprogramming. Insulin-like growth factor 1 (IGF1) and phosphoinositol 3-kinase (PI3K) acted upstream of Akt whereas the mitochondrial target of rapamycin complex 1 (mTORC1) and forkhead box o3 (Foxo3a) acted downstream of Akt to influence fibroblast-to-cardiomyocyte reprogramming. These findings provide insights into the molecular basis of cardiac reprogramming and represent an important step toward further application of this technique. PMID- 26354123 TI - Automated measurement of mouse social behaviors using depth sensing, video tracking, and machine learning. AB - A lack of automated, quantitative, and accurate assessment of social behaviors in mammalian animal models has limited progress toward understanding mechanisms underlying social interactions and their disorders such as autism. Here we present a new integrated hardware and software system that combines video tracking, depth sensing, and machine learning for automatic detection and quantification of social behaviors involving close and dynamic interactions between two mice of different coat colors in their home cage. We designed a hardware setup that integrates traditional video cameras with a depth camera, developed computer vision tools to extract the body "pose" of individual animals in a social context, and used a supervised learning algorithm to classify several well-described social behaviors. We validated the robustness of the automated classifiers in various experimental settings and used them to examine how genetic background, such as that of Black and Tan Brachyury (BTBR) mice (a previously reported autism model), influences social behavior. Our integrated approach allows for rapid, automated measurement of social behaviors across diverse experimental designs and also affords the ability to develop new, objective behavioral metrics. PMID- 26354122 TI - Population, genetic, and antigenic diversity of the apicomplexan Eimeria tenella and their relevance to vaccine development. AB - The phylum Apicomplexa includes serious pathogens of humans and animals. Understanding the distribution and population structure of these protozoan parasites is of fundamental importance to explain disease epidemiology and develop sustainable controls. Predicting the likely efficacy and longevity of subunit vaccines in field populations relies on knowledge of relevant preexisting antigenic diversity, population structure, the likelihood of coinfection by genetically distinct strains, and the efficiency of cross-fertilization. All four of these factors have been investigated for Plasmodium species parasites, revealing both clonal and panmictic population structures with exceptional polymorphism associated with immunoprotective antigens such as apical membrane antigen 1 (AMA1). For the coccidian Toxoplasma gondii only genomic diversity and population structure have been defined in depth so far; for the closely related Eimeria species, all four variables are currently unknown. Using Eimeria tenella, a major cause of the enteric disease coccidiosis, which exerts a profound effect on chicken productivity and welfare, we determined population structure, genotype distribution, and likelihood of cross-fertilization during coinfection and also investigated the extent of naturally occurring antigenic diversity for the E. tenella AMA1 homolog. Using genome-wide Sequenom SNP-based haplotyping, targeted sequencing, and single-cell genotyping, we show that in this coccidian the functionality of EtAMA1 appears to outweigh immune evasion. This result is in direct contrast to the situation in Plasmodium and most likely is underpinned by the biology of the direct and acute coccidian life cycle in the definitive host. PMID- 26354124 TI - Ion channel degeneracy enables robust and tunable neuronal firing rates. AB - Firing rate is an important means of encoding information in the nervous system. To reliably encode a wide range of signals, neurons need to achieve a broad range of firing frequencies and to move smoothly between low and high firing rates. This can be achieved with specific ionic currents, such as A-type potassium currents, which can linearize the frequency-input current curve. By applying recently developed mathematical tools to a number of biophysical neuron models, we show how currents that are classically thought to permit low firing rates can paradoxically cause a jump to a high minimum firing rate when expressed at higher levels. Consequently, achieving and maintaining a low firing rate is surprisingly difficult and fragile in a biological context. This difficulty can be overcome via interactions between multiple currents, implying a need for ion channel degeneracy in the tuning of neuronal properties. PMID- 26354125 TI - Corneal infections in the 21st century. AB - Ninety years ago, the first issue of the Postgraduate Medical Journal published a review of an article written by Mr Robert Lindsay-Rea, a consultant ophthalmic surgeon in the Western Ophthalmic Hospital and an oculist in the West End Hospital for Nervous Diseases, entitled "A preliminary report on the treatment of keratitis". Today, microbial keratitis remains an important cause of avoidable visual impairment in the world. The aetiology of microbial keratitis has changed greatly over the past century due to the discovery of antibiotics, improvement in sanitation and education, the rising trend of contact lens wear and increased air travel. Significant advances have also been made in our understanding and management of this important disorder. This article highlights some of these changes and discusses the current management and research. PMID- 26354127 TI - [Evidence informed decisions in the land of compromise]. PMID- 26354128 TI - Information overload in healthcare: too much of a good thing? AB - The rapidly growing production of healthcare information - both scientific and popular - increasingly leads to a situation of information overload affecting all actors of the healthcare system and threatening to impede the adoption of evidence-based practice. In preparation for the 2015 Cochrane Colloquium in Vienna, we discuss the issues faced by three major actors of this system: patients, healthcare practitioners, and systematic reviewers. We analyze their situation through the concept of "filter failure", positing that the main problem is not that there is "too much information", but that the traditional means of managing and evaluating information are ill-suited to the realities of the digital age. Some of the major instances of filter failure are inadequate information retrieval systems for point-of-care settings, the problem of identifying all relevant evidence in an exceedingly diverse landscape of information resources, and the very basic lack of health information literacy, concerning not only the general public. Finally, we give an overview of proposed solutions to the problem of information overload. These new or adapted filtering systems include adapting review literature to the specific needs of practitioners or patients, technological improvements to information systems, strengthening the roles of intermediaries, as well as improving health literacy. PMID- 26354129 TI - [HTA goes Europe: European collaboration on joint assessment and methodological issues becomes reality]. AB - INTRODUCTION: The standardisation of European HTA and thus the reduction of redundancies require clearly defined processes and methods. The HTA Core Model(r), a tool developed by the European Network EUnetHTA, is intended to ensure the transparent production of standardised and high-quality assessments in international collaboration. METHODS: The present paper describes the experience with already published EUnetHTA assessments as well as possibilities for national/local adaptations of these assessments. The integration of jointly developed methods in routine processes of individual HTA agencies will be explained on the basis of a selected example. Further methodological initiatives in Europe will be presented. RESULTS: So far, EUnetHTA has published four rapid assessments conducted through European cooperation between 6-9 HTA institutes during Joint Action 2 (2012-2015). Two assessments dealt with pharmaceuticals and two with non-pharmaceutical interventions. The overall duration of these assessments ranged from 7 to 9 months. There is initial information about the frequency and manner in which these assessments have been used for national/local HTA reports. According to a survey, a total of 28 HTA institutes have indicated that they want to make use of these assessments in their own context. In Austria, the Ludwig Boltzmann Institute for Health Technology Assessment (LBI-HTA) has produced two reports based on EUnetHTA assessments. A further step towards cross border collaboration and harmonisation is the implementation of these tools in a national and regional context. Beginning in 2015 the LBI-HTA will adjust two programme lines to the format of the HTA Core Model(r) in order to increase the transferability of HTAs and to reduce redundancies. DISCUSSION: Barriers to European collaboration include the relevance of topics for individual HTA institutes and the timing of joint assessments. Implementing commonly developed methods as standard practice in local/national HTA institutes is mainly impeded by legislative requirements. CONCLUSION: Despite the initial positive experiences with international collaboration on specific topics and methods, the coming years will have to prove whether existing barriers can be overcome effectively. PMID- 26354130 TI - [Practical experience with overviews of reviews--valuable decision aid or academic exercise?]. AB - The "overview of reviews" has evolved as a method to aggregate information from systematic reviews. Based on research projects conducted by two Austrian institutions, this article aims to point out methods and perceived strengths and limitations of overviews of reviews and to discuss their application and constraints for different healthcare settings. The six analysed projects differed in their objectives as well as in the corresponding methodology. We identified the following strengths of the overviews of reviews performed: the overview of the evidence base on an issue, the rapid detection of the results of numerous reviews, the demonstration of evidence gaps and potential savings in time and resources. At the same time, the methodology could lead to a loss of information, limited relevance and to uncertainties regarding the robustness of the overall results. However, the heterogeneity of the methods used shows that the development of methods for overviews of reviews is still ongoing. Whether overviews of reviews provide valuable decision support depends on the research question and realistic expectations towards the method. PMID- 26354131 TI - Health technology assessment of medical devices: What is different? An overview of three European projects. AB - BACKGROUND: With the growing use and importance of health technology assessment (HTA) in decision making during recent years, health technology assessors, decision makers and stakeholders are confronted with methodological challenges due to specific characteristics of health technologies (e. g., pharmaceuticals, diagnostic tests, screening programs), their developmental environment, and their regulation process. Being aware of the necessity to use HTA as a policy instrument for sustainable health care systems in a regulatory environment of decentralized Conformite Europeenne (CE) marking, the European Union (EU) is increasingly supporting the development of methods for the assessment of medical devices (MD) on different levels: within the scope of European research projects and within joint assessment activities of the member states of the European network for Health Technology Assessment (EUnetHTA). OBJECTIVE: First, this article describes three projects: MedtecHTA-Methods for Health Technology Assessment of Medical Devices, a European Perspective Work Package 3 (WP3), Comparative Effectiveness of Medical Devices led by the University for Health Sciences, Medical Informatics and Technology (UMIT). Second, we discuss the experiences of the Ludwig Boltzmann Institute Health Technology Assessment (LBI HTA) with the joint production of rapid assessments of medical devices by several European HTA agencies within EUnetHTA. Third, a brief outline is given of the framework of joint methodological guideline elaboration by the EUnetHTA partner organizations because a guideline for therapeutic MD is also being developed here. METHODS: We will describe aims, methods and some preliminary results of MedtecHTA and EUnetHTA Joint Action 2 Work Package 5 Strand B (WP5B) applying the HTA Core Model for Rapid Assessment for national adaptation and reporting, and give an overview of the development process of methodological guidelines within WP 7 of EUnetHTA Joint Action 2. RESULTS: Based on a literature review in MedtecHTA WP3 incremental development, context dependency and the physical mode of action of MD were identified as those characteristics making therapeutic MD different from drugs with regard to evaluation methods. In addition, regulation does not stipulate clinical trials. These characteristics were also identified as challenges for the production of joint assessments of MD within the HTA network EUnetHTA. Furthermore, adequate timing of assessment production, the variety of involved manufacturers, the non-transparent regulation process of MD in Europe and the often poor evidence base pose a challenge to EUnetHTA assessors. As a consequence, processes and methods for the joint production of rapid assessments must be continuously adapted and improved. DISCUSSION: Research on HTA methods for the assessment of MD tries to provide tools to deal with rapidly developing devices during evidence generation, dependence of clinical effectiveness of MD on user experience and context factors. There are also tools to integrate evidence from different sources adjusting for different levels of validity, but these methods are not established and need high epidemiological and statistical expertise. A framework for deciding whether additional evidence is needed to reduce uncertainty regarding safety, clinical effectiveness and cost effectiveness will be adapted to MD. The whole process of evidence generation before and after market access has to be considered to provide an environment for conclusive HTA recommendations informing health care decision making. In Joint Action 2, EUnetHTA develops transparent processes for the early dialogue with stakeholders and fosters dissemination of appropriate HTA methods. In the case of MD, there are special accumulated needs for such efforts. PMID- 26354132 TI - [Guideline development: Going from evidence to recommendations. Challenges and opportunities--a methodologist's view]. AB - The development of evidence-based guidelines is an interdisciplinary process in which methodologists play an important role. In addition to creating new or assessing existing systematic reviews as a basis for evidence-based decision making, methodologists can support the entire development process. Due to the increasing complexity of methods and the information overload of available publications, cooperation between the involved experts (especially clinicians and methodologists, but also patient representatives) is essential in order to develop reliable, acceptable and practical guidelines. This article looks at eight key points of the guideline development process (transparency, conflicts of interest, composition of guideline development group, establishing evidence foundation, development and formulation of recommendations, external review and updating) from the perspective of methodologists, and highlights problems, challenges and solution approaches. The earliest possible involvement of methodologists, a clear and a--for non-methodologists--understandable presentation of the best available evidence, the integration of methodologists in the creation and formulation of recommendations (systematic, evidence-based decision-making process) and cooperation between the participating experts are essential to improve the development process of evidence-based guidelines. PMID- 26354133 TI - Oncotyrol--Center for Personalized Cancer Medicine: Methods and Applications of Health Technology Assessment and Outcomes Research. AB - BACKGROUND: The Oncotyrol - Center for Personalized Cancer Medicine is an international and interdisciplinary alliance combining research and commercial competencies to accelerate the development, evaluation and translation of personalized healthcare strategies in cancer. The philosophy of Oncotyrol is to collaborate with relevant stakeholders and advance knowledge "from bench to bedside to population and back". Oncotyrol is funded through the COMET Excellence Program by the Austrian government via the national Austrian Research Promotion Agency (FFG). This article focuses on the role of health technology assessment (HTA) and outcomes research in personalized cancer medicine in the context of Oncotyrol. METHODS: Oncotyrol, which currently comprises approximately 20 individual projects, has four research areas: Area 1: Biomarker and Drug Target Identification; Area 2: Assay Development and Drug Screening; Area 3: Innovative Therapies; Area 4: Health Technology Assessment and Bioinformatics. Area 4 translates the results from Areas 1 to 3 to populations and society and reports them back to Area 3 to inform clinical studies and guidelines, and to Areas 1 and 2 to guide further research and development. RESULTS: In a series of international expert workshops, the Oncotyrol International Expert Task Force for Personalized Cancer Medicine developed the Methodological Framework for Early Health Technology Assessment and Decision Modeling in Cancer and practical guidelines in this field. Further projects included applications in the fields of sequential treatment of patients with chronic myeloid leukemia (CML), benefit harm and cost-effectiveness evaluation of prostate cancer screening, effectiveness and cost-effectiveness of multiple cervical cancer screening strategies, and benefits and cost-effectiveness of genomic test-based treatment strategies in breast cancer. CONCLUSION: An interdisciplinary setting as generated in Oncotyrol provides unique opportunities such as systematically coordinating lab and bench research, product development, clinical studies and decision science/HTA and transparent joint planning of research and development with a partnership of researchers, manufacturers and health policy decision makers. However, generating a joint research and legal framework with numerous partners from different sectors can be challenging, particularly in the starting period of such an endeavor. The journey to translational personalized medicine through multidisciplinary collaborations may still be long and difficult, but it is evident that it must be continued to turn vision into reality. PMID- 26354134 TI - [How evidence-based are print- and online mass media in Austria? A quantitative analysis]. AB - We rated the body of evidence for 219 health-related questions that had been covered by 990 media articles in Austrian print and online media. In 59.5 % of these articles, the evidence for medical facts is reported in a highly distorted (exaggerated or understated) manner; only 10.8 % adequately reflect the actual strength of evidence. While 61.3% of the articles imply that the reported effects are based on the highest level of evidence, it really only applies to 2.6% of the articles. Compared to quality media, tabloid media report in a more distorted way. However, this is mainly due to a different subject coverage, since the degree of distorted reporting does not significantly differ for subjects covered by both tabloid and quality media. Online media do not report in a more distorted way than print media, with the exception of the newspaper "Der Standard". A clear difference can be seen in the reporting on different subjects. Articles on medications regulated by governmental authorities or interventions which only physicians are allowed to perform were significantly less distorted than articles on nutritional supplements or interventions that may be provided by non-physician staff. Reports on cosmetic or weight loss interventions were most distorted. PMID- 26354135 TI - [Comparative evaluation of information products regarding cancer screening of German-speaking cancer organizations]. AB - BACKGROUND: Evidence-based information materials about the pros and cons of cancer screening are important sources for men and women to decide for or against cancer screening. The aim of this paper was to compare recommendations from different cancer institutions in German-speaking countries (Austria, Germany, and Switzerland) regarding screening for breast, cervix, colon, and prostate cancer and to assess the quality and development process of patient information materials. METHODS: Relevant information material was identified through web searches and personal contact with cancer institutions. To achieve our objective, we employed a qualitative approach. The quality of 22 patient information materials was analysed based on established guidance by Bunge et al. In addition, we conducted guided interviews about the process of developing information materials with decision-makers of cancer institutes. RESULTS: Overall, major discrepancies in cancer screening recommendations exist among the Austrian, German, and Swiss cancer institutes. Process evaluation revealed that crucial steps of quality assurance, such as assembling a multi-disciplinary panel, assessing conflicts of interest, or transparency regarding funding sources, have frequently not been undertaken. All information materials had substantial quality deficits in multiple areas. Three out of four institutes issued information materials that met fewer than half of the quality criteria. CONCLUSION: Most patient information materials of cancer institutes in German-speaking countries are fraught with substantial deficits and do not provide an objective source for patients to be able to make an informed decision for or against cancer screening. PMID- 26354136 TI - [Breast cancer screening in Austria: Key figures, age limits, screening intervals and evidence]. AB - In January 2014, the first nationwide quality-assured breast cancer screening program addressing women aged >= 40 years was introduced in Austria. As part of the process of developing a patient information leaflet, the Evidence Based Medicine (EBM) Review Center of the Medical University of Graz was charged with the task of assessing the potential benefits and harms of breast cancer screening from the available evidence. Based on these results, key figures were derived for mortality, false-positive and false-negative mammography results, and overdiagnosis, considering Austria-specific incidence rates for breast cancer and breast cancer mortality. Furthermore, the current evidence regarding age limits and screening interval, which were the subjects of controversial public discussions, was analyzed. A systematic search for primary and secondary literature was performed and additional evidence was screened, e. g., evaluation reports of European breast cancer screening programs. On the basis of the available evidence and of the Austrian breast cancer mortality and incidence rates, it can be assumed that - depending on the age group - 1 to 4 breast cancer deaths can be avoided per 1,000 women screened in a structured breast cancer screening program, while the overall mortality remains unchanged. On the other hand, 150 to 200 of these 1,000 women will be affected by false-positive results and 1 to 9 women by overdiagnosis due to the structured breast cancer screening. Therefore, the overall benefit-harm balance is uncertain. If women from 40 to 44 or above 70 years of age are considered, who can also participate in the Austrian screening program, even a negative benefit-harm balance seems possible. However, with the implementation of quality standards in breast cancer screening and the dissemination of a patient information leaflet, an improvement in the medical treatment situation, specifically in terms of informed decision-making, can be expected. PMID- 26354137 TI - [Report from general practice: evidence for mature patients]. PMID- 26354138 TI - [Report from general practice: health technology assessment at Health Austria GmbH]. PMID- 26354139 TI - [An evidence-based healthcare system and the role of the healthcare professions]. AB - An evidence-based healthcare system necessitates a new role allocation and new role definitions of the players. By means of professional delegation, physician nurse substitution and adoption of new professional functions, which so far have not been part of their professional profiles, nurses, midwives and allied health professionals will adopt a broad spectrum of new responsibilities. At present, nurses, midwives and allied health professionals lack basic scientific competencies and opportunities to acquire skills in evidence-based practice. A reliable link between evidence-generating sciences in nursing, midwifery and allied health professions and clinical practice is missing. In the future, an increase of academically qualified health professionals and a new skills mix within each profession might promote active and effective participation in an evidence-based healthcare system. (As supplied by author). PMID- 26354140 TI - [Implementation and evaluation of error prevention measures in surgical clinics: Results of a current online survey]. AB - In the autumn of 2014, more than 3,000 surgeons completed an online questionnaire asking for the prevalence and efficiency of instruments to prevent adverse events within surgical departments in Germany. About 90 % of the respondents stated that perioperative checklists, preoperative marking of the surgical site and the documentation of hospital infections had been implemented in their institution; and 75 % of the institutions had introduced critical incident reporting systems (CIRS), morbidity and mortality conferences and identification bracelets for patients. The surgeons were asked to rank the different instruments for the prevention of adverse events. According to the respondents, preoperative marking of the surgical site and the use of checklists were at the top of the efficacy ranking, followed by an introductory course for surgeons starting work in a hospital or when new devices became available. Only 50 % of the responding surgeons perceived CIRS as being efficient. Overall, the answers showed that instruments to increase patient safety were commonly available in surgical departments. On the other hand, there is still room for improvement in daily practice. PMID- 26354141 TI - Hydroxyapatite-intertwined hybrid nanofibres for the mineralization of osteoblasts. AB - Advances in tissue engineering have enabled the development of bioactive composite materials to generate biomimetic nanofibrous scaffolds for bone replacement therapies. Polymeric biocomposite nanofibrous scaffolds architecturally mimic the native extracellular matrix (ECM), delivering tremendous regenerative potential for bone tissue engineering. In the present study, biocompatible poly(l-lactic acid)-co-poly(epsilon-caprolactone)-silk fibroin-hydroxyapatite-hyaluronic acid (PLACL-SF-HaP-HA) nanofibrous scaffolds were fabricated by electrospinning to mimic the native ECM. The developed nanofibrous scaffolds were characterized in terms of fibre morphology, functional group, hydrophilicity and mechanical strength, using SEM, FTIR, contact angle and tabletop tensile-tester, respectively. The nanofibrous scaffolds showed a higher level of pore size and increased porosity of up to 95% for the exchange of nutrients and metabolic wastes. The fibre diameters obtained were in the range of around 255 +/- 13.4-789 +/- 22.41 nm. Osteoblasts cultured on PLACL-SF-HaP-HA showed a significantly (p < 0.001) higher level of proliferation (53%) and increased osteogenic differentiation and mineralization (63%) for the inclusion of bioactive molecules SF-HA. Energy-dispersive X-ray analysis (EDX) data proved that the presence of calcium and phosphorous in PLACL-SF-HaP-HA nanofibrous scaffolds was greater than in the other nanofibrous scaffolds with cultured osteoblasts. The obtained results for functionalized PLACL-SF-HaP-HA nanofibrous scaffolds proved them to be a potential biocomposite for bone tissue engineering. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26354143 TI - Amplified Rate Acceleration by Simultaneous Up-Regulation of Multiple Active Sites in an Endo-Functionalized Porous Capsule. AB - Using the hydrolysis of epoxides in water as a model reaction, the effect of multiple active sites on Michaelis-Menten compliant rate accelerations in a porous capsule is demonstrated. The capsule is a water-soluble Ih-symmetry Keplerate-type complex of the form, [{Mo(VI)6O21(H2O)6}12{Mo(V)2O4(L)}30](42-), in which 12 pentagonal "ligands," {(Mo(VI))Mo(VI)5O21(H2O)6}(6-), are coordinated to 30 dimolybdenum sites, {Mo(V)2O4L}(1+) (L = an endohedrally coordinated eta(2) bound carboxylate anion), resulting in 20 Mo9O9 pores. When "up-regulated" by removal of ca. one-third of the blocking ligands, L, an equal number of dimolybdenum sites are activated, and the newly freed-up space allows for encapsulation of nearly twice as many substrate guests, leading to a larger effective molarity (amplification), and an increase in the rate acceleration (k(cat)/k(uncat)) from 16,000 to an enzyme-like value of 182,800. PMID- 26354142 TI - Identification of late-onset hypogonadism in middle-aged and elderly men from a community of China. AB - In this study, we investigated the essential criteria for late-onset hypogonadism (LOH) syndrome based on the presence of symptoms associated with low testosterone levels in Han Chinese men. Blood tests for total testosterone (TT) and sex hormone-binding globulin (SHBG) were performed, and the aging male symptoms (AMS) questionnaire was conducted in a randomly selected cohort composed of 944 Chinese men aged 40 to 79 years from nine urban communities. Three sexual symptoms (decreased ability/frequency of sexual activity, decreased number of morning erections, and decreased libido) were confirmed to be related to the total and free testosterone levels. The thresholds for TT were approximately 12.55 nmol l-1 for a decreased ability/frequency to perform sex, 12.55 nmol l-1 for decreased frequency of morning erections, and 14.35 nmol l-1 for decreased sexual desire. The calculated free testosterone (CFT) thresholds for these three sexual symptoms were 281.14, 264.90, and 287.21 pmol l-1 , respectively. TT <13.21 nmol l-1 (OR = 1.4, 95%CI: 1.0-1.9, P = 0.037) or CFT <268.89 pmol l-1 (OR = 1.5, 95%CI: 1.1-20, P = 0.020) was associated with an increase in the aforementioned three sexual symptoms. The prevalence of LOH was 9.1% under the criteria, including all three sexual symptoms with TT levels <13.21 nmol l-1 and CFT levels <268.89 pmol l-1 . Our results may improve the diagnostic accuracy of LOH in older men. PMID- 26354144 TI - Review of combined liver and kidney transplantation in children. AB - In this review, we focused on CLKT with regard to indication, results, outcome, and future developments. PH1 is one of the most common diagnoses for adult and pediatric patients qualifying for CLKT. The other major indication for combined transplantation is ARPKD. CLKT appears to be superior to sequential liver and kidney transplantation in the majority of patients and overall results following CLKT are now good, even in small children. Clinical observations suggest that there is an immunological advantage of CLKT in comparison with isolated liver or kidney transplantation. More clinical studies are necessary to identify the best candidates for CLKT while the availability of donor organs is low. PMID- 26354145 TI - Teaching brain-machine interfaces as an alternative paradigm to neuroprosthetics control. AB - Brain-machine interfaces (BMI) usually decode movement parameters from cortical activity to control neuroprostheses. This requires subjects to learn to modulate their brain activity to convey all necessary information, thus imposing natural limits on the complexity of tasks that can be performed. Here we demonstrate an alternative and complementary BMI paradigm that overcomes that limitation by decoding cognitive brain signals associated with monitoring processes relevant for achieving goals. In our approach the neuroprosthesis executes actions that the subject evaluates as erroneous or correct, and exploits the brain correlates of this assessment to learn suitable motor behaviours. Results show that, after a short user's training period, this teaching BMI paradigm operated three different neuroprostheses and generalized across several targets. Our results further support that these error-related signals reflect a task-independent monitoring mechanism in the brain, making this teaching paradigm scalable. We anticipate this BMI approach to become a key component of any neuroprosthesis that mimics natural motor control as it enables continuous adaptation in the absence of explicit information about goals. Furthermore, our paradigm can seamlessly incorporate other cognitive signals and conventional neuroprosthetic approaches, invasive or non-invasive, to enlarge the range and complexity of tasks that can be accomplished. PMID- 26354147 TI - Validation of the Italian Version of the Morningness-Eveningness Questionnaire for Adolescents by A. Lancry and Th. Arbault. AB - This study aimed to validate the Italian version of the Morningness-Eveningness questionnaire for adolescents by Lancry and Arbault. The Morningness-Eveningness Questionnaire by Lancry and Arbault was translated from French into Italian by using forward-backward translation. Students aged 11-15 years old were enrolled from two schools in Milan (Italia). Validation of the questionnaire was performed in subsequent phases. A pre-test was given to 66 students aged 11-15 years (males 57.4%, females 42.6%) from a convenience sample. Syntactic aspects of the pre test were improved, and the questionnaire in a revised version was re administered to 292 students of same age (males 43.8%, females 54.1%) from a convenience sample. Factor analysis was performed on pre-test data, using the principal component method accounting for Morningness-Eveningness. Problematic items possibly uncorrelated with the extracted factor were identified, and reliability produced a Cronbach's Alpha close to 0.7. In the test phase factor analysis was performed using the principal component method. Based on reliability analyses, we excluded a number of items because of their low performance, giving rise to a Cronbach's Alpha of 0.819. Pearson product-moment external correlations between Morningness-Eveningness disposition and temperament, behavioral, and cognitive aspects were evaluated. A factor analysis, Cronbach's alpha and concurrent validity coefficients with disposition, behavior, and cognition, were performed, suggesting potential reliability and validity. The questionnaire is a useful and relevant tool for measuring Morningness-Eveningness disposition in adolescents, which has seldom been investigated with adequate psychometric instruments. PMID- 26354146 TI - Quantitative Proteomic Analysis of Enriched Nuclear Fractions from BK Polyomavirus-Infected Primary Renal Proximal Tubule Epithelial Cells. AB - Polyomaviruses are a family of small DNA viruses that are associated with a number of severe human diseases, particularly in immunocompromised individuals. The detailed virus-host interactions during lytic polyomavirus infection are not fully understood. Here, we report the first nuclear proteomic study with BK polyomavirus (BKPyV) in a primary renal proximal tubule epithelial cell culture system using stable isotope labeling by amino acids in cell culture (SILAC) proteomic profiling coupled with liquid chromatography-tandem mass spectrometry. We demonstrated the feasibility of SILAC labeling in these primary cells and subsequently performed reciprocal labeling-infection experiments to identify proteins that are altered by BKPyV infection. Our analyses revealed specific proteins that are significantly up- or down-regulated in the infected nuclear proteome. The genes encoding many of these proteins were not identified in a previous microarray study, suggesting that differential regulation of these proteins may be independent of transcriptional control. Western blotting experiments verified the SILAC proteomic findings. Finally, pathway and network analyses indicated that the host cell DNA damage response signaling and DNA repair pathways are among the cellular processes most affected at the protein level during polyomavirus infection. Our study provides a comprehensive view of the host nuclear proteomic changes during polyomavirus lytic infection and suggests potential novel host factors required for a productive polyomavirus infection. PMID- 26354148 TI - Consensus Communication on Early Peanut Introduction and Prevention of Peanut Allergy in High-Risk Infants. AB - The purpose of this brief communication is to highlight emerging evidence regarding potential benefits of supporting early rather than delayed peanut introduction during the period of complementary food introduction in infants. This document should be considered as interim guidance based on consensus among the following organizations: American Academy of Allergy, Asthma, and Immunology, American Academy of Pediatrics, American College of Allergy, Asthma, and Immunology, Australasian Society of Clinical Immunology and Allergy, Canadian Society of Allergy and Clinical Immunology, European Academy of Allergy and Clinical Immunology, Israel Association of Allergy and Clinical Immunology, Japanese Society for Allergology, Society for Pediatric Dermatology, and World Allergy Organization. More formal guidelines regarding early-life, complementary feeding practices and the risk of allergy development will follow in the next year from the National Institute of Allergy and Infectious Diseases-sponsored Working Group and the European Academy of Allergy and Clinical Immunology. PMID- 26354151 TI - Kinetic Analysis as a Tool to Distinguish Pathway Complexity in Molecular Assembly: An Unexpected Outcome of Structures in Competition. AB - While the sensitive dependence of the functional characteristics of self assembled nanofibers on the molecular structure of their building blocks is well known, the crucial influence of the dynamics of the assembly process is often overlooked. For natural protein-based fibrils, various aggregation mechanisms have been demonstrated, from simple primary nucleation to secondary nucleation and off-pathway aggregation. Similar pathway complexity has recently been described in synthetic supramolecular polymers and has been shown to be intimately linked to their morphology. We outline a general method to investigate the consequences of the presence of multiple assembly pathways, and show how kinetic analysis can be used to distinguish different assembly mechanisms. We illustrate our combined experimental and theoretical approach by studying the aggregation of chiral bipyridine-extended 1,3,5-benzenetricarboxamides (BiPy-1) in n-butanol as a model system. Our workflow consists of nonlinear least-squares analysis of steady-state spectroscopic measurements, which cannot provide conclusive mechanistic information but yields the equilibrium constants of the self-assembly process as constraints for subsequent kinetic analysis. Furthermore, kinetic nucleation-elongation models based on one and two competing pathways are used to interpret time-dependent spectroscopic measurements acquired using stop-flow and temperature-jump methods. Thus, we reveal that the sharp transition observed in the aggregation process of BiPy-1 cannot be explained by a single cooperative pathway, but can be described by a competitive two-pathway mechanism. This work provides a general tool for analyzing supramolecular polymerizations and establishing energetic landscapes, leading to mechanistic insights that at first sight may seem unexpected and counterintuitive. PMID- 26354149 TI - Global Gene Expression Analysis in PKCalpha-/- Mouse Skin Reveals Structural Changes in the Dermis and Defective Wound Granulation Tissue. AB - The skin's mechanical integrity is maintained by an organized and robust dermal extracellular matrix (ECM). Resistance to mechanical disruption hinges primarily on homeostasis of the dermal collagen fibril architecture, which is regulated, at least in part, by members of the small leucine-rich proteoglycan (SLRP) family. Here we present data linking protein kinase C alpha (PKCalpha) to the regulated expression of multiple ECM components including SLRPs. Global microarray profiling reveals deficiencies in ECM gene expression in PKCalpha-/- skin correlating with abnormal collagen fibril morphology, disorganized dermal architecture, and reduced skin strength. Detailed analysis of the skin and wounds from wild-type and PKCalpha-/- mice reveals a failure to upregulate collagen and other ECM components in response to injury, resulting in delayed granulation tissue deposition in PKCalpha-/- wounds. Thus, our data reveal a previously unappreciated role for PKCalpha in the regulation of ECM structure and deposition during skin wound healing. PMID- 26354152 TI - Comparison of stress-induced and LPS-induced depressive-like behaviors and the alterations of central proinflammatory cytokines mRNA in rats. AB - Although proinflammatory cytokine changes in depression have been studied widely, few investigations have searched for specific and common changes in cytokines. In the present study, two animal models of depression were compared: a chronic stress model using forced swim stress and an immune activation model using repeated central lipopolysaccharide (LPS) infusion. The levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6 mRNA were examined in the brain regions of the prefrontal cortex, amygdala, and hippocampus using real-time polymerase chain reaction (RT-PCR). It was found that both chronic swim stress and repeated central LPS infusion induced depressive-like behaviors, including decreased body weight, reduced saccharin preference, and increased immobility time or shortened latency of immobility in the tail suspension test. Central TNF alpha mRNA expression was elevated in both models and central IL-6 mRNA expression was unchanged in both models. Central IL-1beta mRNA expression was increased only in the chronic immune activation model. The findings from this study suggest that TNF-alpha may be a common risk factor for inflammation in depressive disorders. PMID- 26354153 TI - Perceived Residential Environment Quality Indicators and neighborhood attachment: A confirmation study on a Chinese sample in Chongqing. AB - This paper concerns people's assessment of their neighborhood of residence in a Chinese urban context. The aim of the study was to verify the factorial structure and the reliability of two instruments originally developed and validated in Italy (the full versions of the Perceived Residential Environment Quality Indicators [PREQIs] and of the Neighborhood Attachment Scale [NAS]) in a different cultural and linguistic context. The instruments consist of 11 scales measuring the PREQIs and one scale measuring neighborhood attachment (NA). The PREQIs scales include items covering four macroevaluative domains of residential environment quality: architectural and urban planning aspects (three scales: Architectural and Town-planning Space, Organization of Accessibility and Roads, Green Areas), sociorelational aspects (one scale: People and Social Relations), functional aspects (four scales: Welfare Services, Recreational Services, Commercial Services, and Transport Services), and contextual aspects (three scales: Pace of Life, Environmental Health, Upkeep and Care). The PREQIs and NAS were included in a self-report questionnaire, which had been translated and back translated from English to Chinese, and was then administered to 340 residents in six districts (differing along various features) of a highly urbanized context in China, the city of Chongqing. Results confirmed the factorial structure of the scales and demonstrated good internal consistency of the indicators, thus reaffirming the results of previous studies carried out in Western urban contexts. The indicators tapping the neighborhood's contextual aspects (i.e., pace of life, environmental health, and upkeep) emerged as most correlated to NA. PMID- 26354154 TI - The Taiwanese Derriford Appearance Scale: The translation and validation of a scale to measure individual responses to living with problems of appearance. AB - The extent of concern about physical appearance is increasingly the subject of scientific study, interventions by health professionals, and media attention. To enable carefully evaluated studies exploring the psychosocial antecedents of appearance distress, and to determine the success of interventions, the Derriford Appearance Scale 24 (DAS24) was developed. This psychometrically sound measure is well used and cited in the appearance psychology field. Outside of a Western context, the extent and impact of appearance distress is less well known. This paper describes the adaptation of the DAS24 for use in Taiwan. A formal translation protocol was followed to adapt the DAS24 into Taiwanese/Cantonese. Two hundred and eight participants from a general population and a visibly different population were recruited in Taipei, Taiwan. These participants completed a test pack administered comprising the translated DAS24, and established measures of anxiety and depression. The scale was analyzed on the basis of classical test theory. A translated DAS Scale comprising 19 items and including three clear factors was the best solution. The scale had good internal consistency, clear convergent validity, and good test-retest reliability. The three factors that emerged were appearance-related social avoidance, social distress, and negative affect. Consistent with expectations, (a) women scored higher than men (greater appearance distress), (b) the cause of appearance difference (burns, cleft lip/palate, etc.) was unrelated to appearance distress, and (c) those with visible differences were more concerned about their appearance than those without. The Taiwanese DAS19 is a user-friendly and psychometrically sound scale that fulfils an important clinical and scientific need. The items that were omitted from the translated version were considered in relation to cultural differences in the experience and expression of shame between Western countries and Taiwan/China, which demands a careful future analysis. PMID- 26354155 TI - Does psychological need satisfaction perceived online enhance well-being? AB - The Internet has been building a new context, in which adolescents and young people complete their academic tasks, do their work, engage in social interaction, and even conduct anonymous identity experimentation. Therefore, it becomes very significant to assess psychological need satisfaction online, and to relate it to well-being. This study investigated the influence on well-being of psychological need satisfaction perceived online and the regulatory role in this relationship of psychological need satisfaction perceived in daily life. A total of 1,727 students from junior and senior high schools and universities in China were surveyed using the Basic Psychological Needs in General scale, the Basic Psychological Needs in the Online World scale, and the Index of Well-Being, Index of General Affect scale. The mean age of the adolescent sample was 17.47 years (ranging from 12.50 to 25.42 years). The results indicated that both need satisfaction perceived online and that perceived in daily life positively predicted psychological well-being, and psychological need satisfaction in daily life qualified the association between psychological need satisfaction perceived online and well-being. In particular, students who perceived higher psychological need satisfaction in daily life were found to benefit from psychological need satisfaction perceived online, but students with low psychological need satisfaction perceived in daily life did not. We suggest that people who perceive lower basic need satisfaction in daily life are more likely to use the Internet for socioaffective regulation and to consider cyberspace as a new world. Thus, need satisfaction perceived online may not transform into "real" happiness. PMID- 26354156 TI - Age-related differences in attention and memory toward emotional stimuli. AB - From the perspectives of time perception and motivation, socioemotional selectivity theory (SST) postulates that in comparison with younger adults, older adults tend to prefer positive stimuli and avoid negative stimuli. Currently the cross-cultural consistency of this positivity effect (PE) is still not clear. While empirical evidence for Western populations is accumulating, the validation of the PE in Asians is still rare. The current study compared 28 younger and 24 older Chinese adults in the processing of emotional information. Eye-tracking and recognition data of participants in processing pictures with positive, negative, or neutral emotional information sampled from the International Affection Picture System were collected. The results showed less negative bias for emotional attention in older adults than in younger adults, whereas for emotional recognition, only younger adults showed a negative bias while older adults showed no bias between negative and positive emotional information. Overall, compared with younger adults, emotional processing was more positive in older adults. It was concluded that Chinese older adults show a PE. PMID- 26354157 TI - The arginine vasopressin V1b receptor gene and prosociality: Mediation role of emotional empathy. AB - The vasopressin V1b receptor (AVPR1B) gene has been shown to be closely associated with bipolar disorder and depression. However, whether it relates to positive social outcomes, such as empathy and prosocial behavior, remains unknown. This study explored the possible role of the AVPR1B gene rs28373064 in empathy and prosociality. A total of 256 men, who were genetically unrelated, non clinical ethnic Han Chinese college students, participated in the study. Prosociality was tested by measuring the prosocial tendencies of cognitive and emotional empathy using the Interpersonal Reactivity Index (IRI). The single nucleotide polymorphism (SNP), rs28373064, was genotyped using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. The results suggest that the AVPR1B gene rs28373064 is linked to emotional empathy and prosociality. The mediation analysis indicated that the effect of the AVPR1B gene on prosociality might be mediated by emotional empathy. This study demonstrated the link between the AVPR1B gene and prosociality and provided evidence that emotional empathy might mediate the relation between the AVPR1B gene and prosociality. PMID- 26354158 TI - Testing the Zimbardo Time Perspective Inventory in the Chinese context. AB - In this study, the authors evaluated the Chinese version of the Zimbardo Time Perspective Inventory (ZTPI). The ZTPI was tested among a sample of 303 university students. A subsample of 51 participants was then asked to complete the ZTPI again along with another set of questionnaires. The five-factor model of a 20-item short version of the ZTPI showed good model fit, internal consistency, and test-retest reliability. The 20-item Chinese version of the ZTPI also provided good validity, showing correlations with other variables in expected directions. Past-Positive was positively correlated with reappraisal and negatively correlated with suppression emotion regulation strategies, and Present Hedonistic was positively correlated with reappraisal emotion regulation strategies. These findings indicate that the ZTPI is a reliable and valid instrument for measuring time perspective in the Chinese setting. PMID- 26354160 TI - Sheathless guide catheter in transradial percutaneous coronary intervention for ST-segment elevation myocardial infarction. AB - OBJECTIVES: The aim of this study was to assess the safety and efficacy of sheathless guide catheters in transradial percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). BACKGROUND: Transradial PCI for STEMI offers significant clinical benefits, including a reduced incidence of vascular complications. As the size of the radial artery is small, the radial artery is frequently damaged in this procedure using large-bore catheters. A sheathless guide catheter offers a solution to this problem as it does not require an introducer sheath. However, the efficacy and safety of sheathless guide catheters remain to be fully determined in emergent transradial PCI for STEMI. METHODS: Data on consecutive STEMI patients undergoing primary PCI at the Sendai Kousei Hospital between September 2010 and May 2013 were analyzed. The primary endpoint was the rate of acute procedural success without access site crossover. Secondary endpoints included door-to-balloon time, fluoroscopy time, volume of contrast, and radial artery stenosis or occlusion rate. RESULTS: We conducted transradial PCI for 478 patients with STEMI using a sheathless guide catheter. Acute procedural success was achieved in 466 patients (97.5%). The median door-to-balloon time was 45 min (range, 15-317 min). The median fluoroscopy time was 16.4 min (range, 10-90 min). The median volume of contrast was 134 mL (range, 31-431 mL). Radial stenosis or occlusion developed in 14 (3.8%) of the 370 evaluable patients. CONCLUSIONS: This study showed that use of a sheathless guide catheter taking a transradial approach was effective and safe in primary PCI for STEMI. (c) 2015 Wiley Periodicals, Inc. PMID- 26354161 TI - Functional MRI of neuronal activation in epilepsy patients with malformations of cortical development. AB - Malformations of cortical development are disturbances in brain formation that arise from abnormalities affecting the processes of cortical development. Surgical treatment of intractable epilepsy in patients with malformations of cortical development requires localization of both epileptogenic and eloquent cortices. Functional magnetic resonance imaging has been shown to detect the reorganization of activation patterns in such patients. The purpose of this study was to determine whether functional reorganization of the primary sensory and motor cortices occurs in patients with epileptogenic malformations of cortical development. Functional MRI data were obtained for 11 patients (four male, seven female) with a mean age of 36 years (range 18-55 years). The mean age at epilepsy onset was 23 years (range 3-55 years). Twelve healthy controls (six male, six female) with mean age of 33 years (range 28-51 years) were also recruited for comparison. High resolution anatomical MRI was used to confirm the presence and the location of the malformation. All imaging experiments were performed using a 3.0T Siemens Tim Trio whole body MRI. Each subject performed four block-paradigm fMRI experiments to study motor and sensory activation for each hand. A total of 132 image sets were collected for each paradigm over 5.5min (2.5s per image). Each paradigm consisted of seven stimulus periods lasting 30s (12 images) and stimulus onset of 30, 90, 150, 210 and 270s. Functional data were obtained from all eligible patients and compared to those of controls. Reorganization and reduction in function in the motor and sensory areas were observed in patients with cortical dysplasia. Patients with polymicrogyria did not present with significant functional reorganization and patients with heterotopias and coexisting polymicrogyria and/or cortical dysplasia had variable patterns of activation. In summary, this study showed evidence of functional reorganization of sensory and motor cortices in patients with cortical dysplasia development. Such information should be carefully considered in surgical planning and treatment. PMID- 26354162 TI - Magnetic resonance imaging of focal cortical dysplasia: Comparison of 3D and 2D fluid attenuated inversion recovery sequences at 3T. AB - PURPOSE: Focal cortical dysplasia (FCD) is a frequent finding in drug resistant epilepsy. The aim of our study was to evaluate an isotropic high-resolution 3 dimensional Fluid-attenuated inversion recovery sequence (3D FLAIR) at 3T in comparison to standard 2D FLAIR in the diagnosis of FCD. MATERIALS AND METHODS: In a prospective study, 19 epilepsy patients with the MR diagnosis of FCD were examined with a sagittal 3D FLAIR sequence with modulated refocusing flip angle (slice thickness 1.10mm) and a 2D FLAIR in the coronal (thk. 3mm) and axial planes (thk. 2mm). Manually placed regions of interest were used for quantitative analysis. Qualitative image analysis was performed by two neuroradiologists in consensus. RESULTS: Contrast between gray and white matter (p <= 0.02), the lesion (p <= 0.031) or hyperintense extension to the ventricle (p <= 0.021) and white matter was significantly higher in 2D than in 3D FLAIR sequences. In the visual analysis there was no difference between 2D and 3D sequences. CONCLUSION: Conventional 2D FLAIR sequences yield a higher image contrast compared to the employed 3D FLAIR sequence in patients with FCDs. Potential advantages of 3D imaging using surface rendering or automated techniques for lesion detection have to be further elucidated. PMID- 26354164 TI - Epilepsy and hippocampal neurodegeneration induced by glutamate decarboxylase inhibitors in awake rats. AB - Glutamic acid decarboxylase (GAD), the enzyme responsible for GABA synthesis, requires pyridoxal phosphate (PLP) as a cofactor. Thiosemicarbazide (TSC) and gamma-glutamyl-hydrazone (PLPGH) inhibit the free PLP-dependent isoform (GAD65) activity after systemic administration, leading to epilepsy in mice and in young, but not in adult rats. However, the competitive GAD inhibitor 3-mercaptopropionic acid (MPA) induces convulsions in both immature and adult rats. In the present study we tested comparatively the epileptogenic and neurotoxic effects of PLPGH, TSC and MPA, administered by microdialysis in the hippocampus of adult awake rats. Cortical EEG and motor behavior were analyzed during the next 2h, and aspartate, glutamate and GABA were measured by HPLC in the microdialysis collected fractions. Twenty-four hours after drug administration rats were fixed for histological analysis of the hippocampus. PLPGH or TSC did not affect the motor behavior, EEG or cellular morphology, although the extracellular concentration of GABA was decreased. In contrast, MPA produced intense wet-dog shakes, EEG epileptiform discharges, a >75% reduction of extracellular GABA levels and remarkable neurodegeneration of the CA1 region, with >80% neuronal loss. The systemic administration of the NMDA glutamate receptor antagonist MK 801 30 min before MPA did not prevent the MPA-induced epilepsy but significantly protected against its neurotoxic effect, reducing neuronal loss to <30%. We conclude that in adult awake rats, drugs acting on PLP availability have only a weak effect on GABA neurotransmission, whereas direct GAD inhibition produced by MPA induces hyperexcitation leading to epilepsy and hippocampal neurodegeneration. Because this degeneration was prevented by the blockade of NMDA receptors, we conclude that it is due to glutamate-mediated excitotoxicity consequent to disinhibition of the hippocampal excitatory circuits. PMID- 26354165 TI - Neuroimaging observations linking neurocysticercosis and mesial temporal lobe epilepsy with hippocampal sclerosis. AB - OBJECTIVE: To test if chronic calcificed neurocysticercosis (cNCC) and hippocampal sclerosis occur more often than by chance ipsilateral to the same brain hemisphere or brain region in mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE-HS) plus neurocysticercosis. This proof-of-concept would provide important evidence of a direct pathogenic relationship between neurocysticercosis and MTLE-HS. METHODS: A cohort of 290 consecutive MTLE-HS surgical patients was studied. A test of proportions was used to analyze if the proportion of patients with a single cNCC lesion matching the same brain hemisphere or region of hippocampal sclerosis was significantly greater than 50%, as expected by the chance. RESULTS: Neuroimaging findings of cNCC were observed in 112 (38.6%) of 290 MTLE-HS patients and a single cNCC lesion occurred in 58 (51.8%) of them. There were no differences in main basal clinical characteristics of MTLE-HS patients with single or multiple cNCC lesions. In patients with single cNCC lesions, the lesion matched the side in which hippocampal sclerosis was observed in 43 (74.1%) patients, a proportion significantly greater than that expected to occur by chance (p=0.008). Neurocysticercosis in temporal lobe was ipsilateral to hippocampal sclerosis in 85.0% of patients and accounted mostly for this result. CONCLUSIONS: This work is a proof-of-concept that the association of neurocysticercosis and MTLE-HS cannot be explained exclusively by patients sharing common biological or socio-economic predisposing variables. Instead, our results suggest the involvement of more direct pathogenic mechanisms like regional inflammation, repetitive seizures or both. Neurocysticercosis within temporal lobes was particularly related with ipsilateral hippocampal sclerosis in MTLE-HS, a finding adding new contributions for understanding MTLE HS plus cNCC or perhaps to other forms of dual pathology in MTLE-HS. PMID- 26354163 TI - Optogenetic tools for modulating and probing the epileptic network. AB - Epilepsy affects roughly 1% of the population worldwide. Although effective treatments with antiepileptic drugs are available, more than 20% of patients have seizures that are refractory to medical therapy and many patients experience adverse effects. Hence, there is a continued need for novel therapies for those patients. A new technique called "optogenetics" may offer a new hope for these refractory patients. Optogenetics is a technology based on the combination of optics and genetics, which can control or record neural activity with light. Following delivery of light-sensitive opsin genes such as channelrhodopsin-2 (ChR2), halorhodopsin (NpHR), and others into brain, excitation or inhibition of specific neurons in precise brain areas can be controlled by illumination at different wavelengths with very high temporal and spatial resolution. Neuromodulation with the optogenetics toolbox have already been shown to be effective at treating seizures in animal models of epilepsy. This review will outline the most recent advances in epilepsy research with optogenetic techniques and discuss how this technology can contribute to our understanding and treatment of epilepsy in the future. PMID- 26354166 TI - Pyruvate dehydrogenase complex deficiency and its relationship with epilepsy frequency--An overview. AB - The pyruvate dehydrogenase complex (PDHc) is a member of a family of multienzyme complexes that provides the link between glycolysis and the tricarboxylic acid (TCA) cycle by catalyzing the physiologically irreversible decarboxylation of various 2-oxoacid substrates to their corresponding acyl-CoA derivatives, NADH and CO2. PDHc deficiency is a metabolic disorder commonly associated with lactic acidosis, progressive neurological and neuromuscular degeneration that vary with age and gender. In this review, we aim to discuss the relationship between occurrence of epilepsy and PDHc deficiency associated with the pyruvate dehydrogenase complex (E1alpha subunit (PDHA1) and E1beta subunit (PDHB)) and PDH phosphatase (PDP) deficiency. PDHc plays a crucial role in the aerobic carbohydrate metabolism and regulates the use of carbohydrate as the source of oxidative energy. In severe PDHc deficiency, the energy deficit impairs brain development in utero resulting in physiological and structural changes in the brain that contributes to the subsequent onset of epileptogenesis. Epileptogenesis in PDHc deficiency is linked to energy failure and abnormal neurotransmitter metabolism that progressively alters neuronal excitability. This metabolic blockage might be restricted via inclusion of ketogenic diet that is broken up by beta-oxidation and directly converting it to acetyl-CoA, and thereby improving the patient's health condition. Genetic counseling is essential as PDHA1 deficiency is X-linked. The demonstration of the X-chromosome localization of PDHA1 resolved a number of questions concerning the variable phenotype displayed by patients with E1 deficiency. Most patients show a broad range of neurological abnormalities, with the severity showing some dependence on the nature of the mutation in the Elalpha gene, while PDHB and PDH phosphatase (PDP) deficiencies are of autosomal recessive inheritance. However, in females, the disorder is further complicated by the pattern of X-chromosome inactivation, i.e., unfavorable lyonization. Furthermore research should focus on epileptogenic animal models; this might pave a new way toward identification of the pathophysiology of this challenging disorder. PMID- 26354167 TI - The ketogenic diet in infants--Advantages of early use. AB - OBJECTIVE: To evaluate the efficacy and safety of the ketogenic diet (KD) in infants (< 1.5 years of age) compared with older children. METHODS: Patients with complete follow-up data of >= 3 months after initiation of the KD were analyzed retrospectively. Infants < 1.5 years at initiation of the KD (Group A) were compared with children > 1.5 years (Group B). RESULTS: 127 children were screened, 115 (Group A: 58/Group B: 57) were included. There were no significant differences between groups with respect to responder rates (63.8% vs. 57.9% at 3 months), but more infants became seizure free (34.5% vs. 19% at 3 months; 32.7% vs. 17.5% at 6 and 12 months). This result remained stable also after termination of the KD (30.6% vs. 3.9% at last follow-up) (p = 0.000). Looking at infants < 9 months of age separately (n = 42), this result was even stronger with significantly more infants being seizure free at 6 and at 12 months (p = 0.005, p = 0.014, respectively). In addition, a significantly higher number of infants remained seizure free in the long-term (p = 0.001). No group differences between infants and children with respect to safety were observed. Overall 52/115 patients (45.21%) reported side effects, but withdrawal of the KD was only necessary in one infant. Acceptance of the KD was better in infants compared with children at 3 months (0 vs. 14, p = 0.000), but became difficult when solid food was introduced (16 vs. 14; n.s.). SIGNIFICANCE: According to our results, the KD is highly effective and well tolerated in infants with epilepsy. Seizure freedom is more often achieved and maintained in infants. Acceptance of the diet is better before the introduction of solid food. Therefore, we recommend the early use of the KD during the course of epilepsy. PMID- 26354168 TI - Enzyme-inducing antiepileptic drugs and fractures in people with epilepsy: A systematic review. AB - OBJECTIVE: People with epilepsy (PWE) have an increased fracture risk, independent of seizures. Antiepileptic drugs are thought to increase this risk, particularly those that induce the hepatic cytochrome P450 enzyme system. We aimed to determine whether PWE treated with enzyme-inducing antiepileptic drugs (EIAEDs) have decreased bone mineral density (BMD), or increased fracture incidence, versus those treated with non-EIAEDs. METHODS: We searched MedLine, EMBase, CENTRAL, and CINAHL prior to November 2014 for all studies comparing fracture risk, or BMD change, in PWE treated for >= 1 year with EIAEDs versus non EIAEDs. RESULTS: Thirteen observational studies met eligibility criteria. These studies, representing 68,973 adult PWE, were significantly heterogeneous, making meta-analysis impossible. Study results were split, with 5 studies showing decreased BMD in EIAED users, 5 studies showing no effect of EIAED on BMD, 2 studies showing increased fracture incidence in EIAED users, and 1 study showing no difference in fracture risk. The largest study (n = 63,259), which was also the most methodologically rigorous, showed an increased hazard ratio of 9-22% for any fracture, and 49-53% for hip fracture, in EIAED users. SIGNIFICANCE: The literature is divided regarding the bone effects of EIAEDs; however, current best evidence supports an increased fracture risk in PWE treated with an EIAED compared to those treated with non-EIAEDs. A single article dominated our review, and other large methodologically rigorous studies are needed to confirm or refute its results. Further small studies, with limited power to control for multiple potentially confounding variables, are not likely to help. PMID- 26354169 TI - Employability in people with epilepsy: A systematic review. AB - OBJECTIVES: People with epilepsy were (PWE) reported to have poorer employment rate. However, the methodologies used differ greatly from one study to another, making global comparison difficult. We aimed to determine the employment rate of PWE globally using a unified definition of employment rate and to summarize the reported positive and negative factors affecting employability in PWE, using a systematic review. METHODS: All studies reporting employment rate of PWE were independently assessed. Employment rate was recalculated according to the standard definition by the Bureau of Labor statistics (BLS) of United States and the International Labour Organization i.e. employment rate is the percentage of employed person over the labor force. RESULTS: Of 95 papers reported on employment status of PWE, adjusted employment rate (aER) was shown to be as low as 14% to as high as 89% with a mean adjusted employment rate of 58%. No significant differences in mean of aER was found between continents, or among Asian countries. Employment rate of people with uncontrolled seizures were reported in 16 papers, with a mean adjusted employed rate of 58%. Psychological factors were less frequently reported as compared to clinical and socio demographical factors, seen in a total of 25 (26%) out of 97 studies. The positive factors leading to successful career in PWE were understudied and needed to be further explored. CONCLUSION: Employability is multifactorial, including clinical, psychological and social factors. The adjusted employment rate of people with uncontrolled seizures is comparable to those with controlled seizures, supporting the need to explore non-clinical factors. PMID- 26354171 TI - Presence of pharmaceuticals and heavy metals in the waters of a Mediterranean coastal wetland: Potential interactions and the influence of the environment. AB - The occurrence of 17 relevant pharmaceuticals and 7 heavy metals in the waters of the Pego-Oliva Marsh Natural Park (Valencia Community, Spain) were monitored. Thirty four zones (including the lagoon and the most important irrigation channels), covering the main land uses and water sources, were selected for sampling. Thirty three of them were contaminated with at least one pharmaceutical. Ibuprofen and codeine were the pharmaceuticals more frequently detected, in concentrations between 4.8 and 1.2 ng/L and a maximum of 59 ng/L and 63 ng/L, respectively. Regarding metals, Zn showed values under the detection limit in all the samples, while Cd, Co, Cr, Cu, Ni and Pb were detected at concentrations lower than the WHO and EU maximum levels for drinking waters. Ni showed significant direct correlations with diazepam, norfloxacin, ofloxacin and fenofibrate, and inverse relationships with ibuprofen, at 99 and 95% of significance. Cu, Co and Cr also showed significant correlations with some of the pharmaceuticals. These interactions could favor the synergistic/antagonistic interactions among pharmaceuticals and metals in the marsh, which can affect its aquatic fauna and flora or even human health. The influences of the water sources, land uses and spatial distribution of both types of contaminants were also studied. PMID- 26354170 TI - Regional homogeneity (ReHo) changes in new onset versus chronic benign epilepsy of childhood with centrotemporal spikes (BECTS): A resting state fMRI study. AB - OBJECTIVE: The purpose of this study was to investigate regional homogeneity (ReHo) in children with new-onset drug-naive Benign Epilepsy with Centrotemporal Spikes (BECTS), chronic BECTS and healthy controls (HC) using the Regional Homogeneity (ReHo) method applied to resting state fMRI data. METHODS: Resting state fMRI data was collected from three groups of children aged 6-13, including new onset drug naive BECTS, chronic BECTS with medication, and HC; the data analyzed by ReHo method. Mandarin school exams scores were acquired and compared across groups. RESULTS: There were three main findings. Firstly, compared with HC, abnormally increased ReHo was observed in bilateral sensorimotor regions in new onset BECTS which normalized or even reversed in the chronic BECTS group. Secondly, enhanced ReHo was found in the left frontal language region in the two BECTS groups, with even higher ReHo value in the chronic group. Lastly, decreased ReHo was found in regions of the default mode network (DMN), bilateral occipital lobes and cerebellum in both the new onset and chronic BECTS groups, lower in chronic BECTS. Behavioral analyses of school scores showed the chronic BECTS group presented significantly lower scores compared to HC (p<.05). SIGNIFICANCE: The coherence of low frequency fluctuations is disrupted in sensorimotor, language and DMN-related regions in new-onset BECTS. Some of these effects seem to be selectively normalized in chronic BECTS, thus allowing us to explore possible chronicity and AED-induced effects on BECTS. Abnormal ReHo in left language and DMN regions could be responsible for impairments of cognitive function. PMID- 26354173 TI - A view from the hospital boardroom. PMID- 26354174 TI - Clinical association of Spirochaetes and Synergistetes with peri-implantitis. AB - OBJECTIVES: The microbial composition of peri-implantitis-associated biofilms may resemble that of periodontitis, with some distinctive differences, as identified by various conventional or molecular detection methods. Yet, the complete microbiome of peri-implantitis awaits further characterization. The present clinical study was undertaken with the aim to investigate the association of Spirochaetes, and the more recently identified phylum Synergistetes, with peri implantitis. MATERIALS AND METHODS: Submucosal biofilms were obtained from single sites of patients with peri-implantitis (n = 43) or individuals with peri-implant health (n = 41). The samples were analysed by fluorescence in situ hybridization (FISH) and epifluorescence microscopy, using 16S rRNA-based oligonucleotide probes for Synergistetes cluster A, subclusters A1 and A2, and Treponema groups I III and IV. RESULTS: Treponema group IV was barely detectable, whereas Treponema groups I-III were detected at low prevalence in health, but their prevalence and numbers were significantly increased in peri-implantitis by 48% and 2.4-log, respectively. Synergistetes cluster A was detected in half of the healthy sites, and its prevalence and numbers were significantly increased in peri-implantitis by 30% and 2.5-log, respectively. No quantitative differences were found between Synergistetes subclusters A1 and A2 numbers, as both increased by 2.8-log. Synergistetes cluster A displayed strong correlations with several clinical peri implant parameters, but Treponema groups I-III only with probing pocket depth. CONCLUSION: The present clinical cross-sectional study demonstrates that Spriochaetes of the Treponema groups I-III, but not group IV, and Synergistetes of the cluster A are highly associated with peri-implantitis. Synergistetes cluster A appears to display a stronger association with peri-implantitis than Spirochaetes. PMID- 26354175 TI - CORR Insights((r)): Does Tranexamic Acid Reduce Blood Loss and Transfusion Requirements Associated With the Periacetabular Osteotomy? PMID- 26354177 TI - Letter to the editor: do complication rates differ by gender after metal-on-metal hip resurfacing arthroplasty? A systematic review. PMID- 26354176 TI - No differences in early results of a hybrid glenoid compared with a pegged implant. AB - BACKGROUND: Glenoid component loosening after total shoulder arthroplasty is one of the most common causes of failure. A hybrid glenoid that uses peripherally cemented pegs and a central press-fit post may improve implant longevity. QUESTIONS/PURPOSES: We asked, compared with polyethylene pegged glenoid implants, do hybrid glenoid implants with a titanium post provide (1) better ingrowth with fewer radiolucencies, (2) better outcome and pain scores, and (3) lower risk of complications and revisions? METHODS: Between 2009 and 2010, 126 patients underwent primary total shoulder arthroplasty for osteoarthritis. Patients were included in this retrospective study if they consented for inclusion in a shoulder arthroplasty registry, had complete baseline and 2-year data, and had complete radiographs. Eighty-three (67%) were available at an average followup of 3.2 years (range, 24-45 months). Forty received a conventional all-polyethylene pegged glenoid and 43 received a hybrid component. During the period in question, four of the participating surgeons used only one implant, and four used only the other; there was one high-volume surgeon in each of the study groups. Radiographs were taken at the 2-year followup and analyzed for radiolucent lines. CT scans were obtained randomly for 10 patients with hybrid glenoid implants to assess bone ongrowth. American Shoulder and Elbow Surgeons score, VAS score, complications and revisions were recorded. RESULTS: At final followup, radiolucent lines between the two study groups were not different (hybrid, 1.0 +/ 0.4; pegged, 1.6 +/- 0.3; mean difference, 0.6; 95% CI, 0.85-1.72; p = 0.323). Final VAS pain scores were not different (hybrid, 1.2 +/- 0.2; pegged, 1.5 +/- 0.3; p = 0.056). Change in American Shoulder and Elbow Surgeons scores were not different (hybrid, 33.7 +/- 7.3; pegged, 35.5 +/- 8.2; p = 0.283). There were no differences in complication risk (hybrid, one of 43 [2.3%]; pegged, three of 40 [7.5%]; relative risk, 2.3; 95% CI, 0.82-3.12; p = 0.061). CONCLUSIONS: With the numbers available and at early followup, there were no differences between the hybrid and pegged glenoids in terms of fixation, functional outcome, pain scores, and complications. CT scans confirmed bone ongrowth on the porous titanium post in a small subcohort of patients. Further studies are needed to determine how this new implant will perform with time. Until then, its use should be initiated with caution. LEVEL OF EVIDENCE: Level III, therapeutic study. PMID- 26354179 TI - Knock-in of a histone H2B-tdTomato reporter into the Rosa26 locus allows visualization of cell nuclei in rats. PMID- 26354178 TI - Incidence and risk factors for hemorrhagic cystitis in unmanipulated haploidentical transplant recipients. AB - BACKGROUND: Hemorrhagic cystitis (HC) is a common complication after hematopoietic allogeneic stem cell transplantation (HSCT) associated with intensity of the conditioning regimen, cyclophosphamide (Cy) therapy, and BK polyomavirus (BKPyV) infection. METHODS: We analyzed 33 consecutive haploidentical (haplo) HSCT recipients transplanted for hematologic diseases. Eleven patients had a previous transplant. Median follow-up was 11 months. Graft versus-host disease (GVHD) prophylaxis consisted of cyclosporine + mycophenolate mofetil and post-HSCT Cy. RESULTS: Thirty-two of 33 patients achieved neutrophil recovery. Cumulative incidence (CI) of platelet recovery was 65%. CI grade II-IV acute GVHD was 44%. Twenty patients developed HC in a median time of 38 days. CI of HC at day 180 was 62%. BKPyV was positive in blood and urine of 91% of patients at HC onset. HC resolved in 18/20 patients. Factors associated with HC were previous transplant (P = 0.01) and occurrence of cytomegalovirus reactivation before HC (P = 0.05). Grade II-IV acute GVHD was not associated with HC (P = 0.62). CI of day 180 viral infections was 73%. Two-year overall survival (OS) was 50%; HC did not impact OS (P = 0.29). CONCLUSION: The incidence of HC after haplo with post-HSCT Cy is high and is associated with morbidity, especially in high-risk patients such as those with a previous transplant history and with impaired immune reconstitution. PMID- 26354180 TI - Hybridization between alien species Rumex obtusifolius and closely related native vulnerable species R. longifolius in a mountain tourist destination. AB - Alien species expand their distribution by transportation network development. Hybridization between alien species Rumex obtusifolius and closely related native vulnerable species R. longifolius was examined in a mountain tourist destination in central Japan. The three taxa were morphologically identified in the field. Stem height and leaf area were greater in R. longifolius than R. obtusifolius; hybrids were intermediate between the two Rumex species. R. longifolius and the hybrids grew mainly in wet land and the river tributary; R. obtusifolius grew mainly at the roadside and in meadows. Hybrid germination rates of pollen and seeds were much lower than for the two Rumex species. Clustering analysis showed the three taxa each formed a cluster. Most hybrids were F1 generation; the possibility was low of introgression into the two Rumex species by backcross. This study clarified that (1) hybridization occurred between R. obtusifolius and R. longifolius because they occurred together in a small area, but grew in different water habitat conditions, and (2) hybridization was mostly F1 generation because hybrid pollen and seed fertility was low. However, we need caution about introgression into R. longifolius by R. obtusifolius in this area because of the slight possibility of F2 generation and backcrosses. PMID- 26354181 TI - IKKepsilon negatively regulates RIG-I via direct phosphorylation. AB - Inhibitor of nuclear factor kappa-B kinase Epsilon (IKKepsilon) is an IKK-related kinase. Despite it was originally discovered as a kinase functionally related to TBK-1, studies entailing gene knockout mouse demonstrated that IKKepsilon is dispensable for interferon induction by viral infection. In this study, we report that IKKepsilon directly phosphorylates a key serine residue within the RNA binding domain of RIG-I (retinoic acid-inducible gene 1) to inhibit RIG-I-mediate innate immune signaling. Using IKKepsilon-deficient MEFs, we found that loss of IKKepsilon resulted in increased cytokine production in response to the activation of cytosolic sensors. Biochemical analyses indicated that IKKepsilon physically associated with and phosphorylated RIG-I. Mass spectrometry analysis identified that IKKepsilon phosphorylated the serine 855 of the RNA-binding pocket of RIG-I carboxyl terminal domain, a residues known to impinge on RNA binding via phosphorylation. Our findings collectively support the conclusion that IKKepsilon modulates innate immune signaling cascades via phosphorylating the RIG-I cytosolic sensor, providing a feedback regulatory mechanism. PMID- 26354182 TI - The Janus face of Darwinian competition. AB - Without competition, organisms would not evolve any meaningful physical or cognitive abilities. Competition can thus be understood as the driving force behind Darwinian evolution. But does this imply that more competitive environments necessarily evolve organisms with more sophisticated cognitive abilities than do less competitive environments? Or is there a tipping point at which competition does more harm than good? We examine the evolution of decision strategies among virtual agents performing a repetitive sampling task in three distinct environments. The environments differ in the degree to which the actions of a competitor can affect the fitness of the sampling agent, and in the variance of the sample. Under weak competition, agents evolve decision strategies that sample often and make accurate decisions, which not only improve their own fitness, but are good for the entire population. Under extreme competition, however, the dark side of the Janus face of Darwinian competition emerges: Agents are forced to sacrifice accuracy for speed and are prevented from sampling as often as higher variance in the environment would require. Modest competition is therefore a good driver for the evolution of cognitive abilities and of the population as a whole, whereas too much competition is devastating. PMID- 26354183 TI - Comparative Proteomic Analysis of Wild-Type and SAP Domain Mutant Foot-and-Mouth Disease Virus-Infected Porcine Cells Identifies the Ubiquitin-Activating Enzyme UBE1 Required for Virus Replication. AB - Leader protein (L(pro)) of foot-and-mouth disease virus (FMDV) manipulates the activities of several host proteins to promote viral replication and pathogenicity. L(pro) has a conserved protein domain SAP that is suggested to subvert interferon (IFN) production to block antiviral responses. However, apart from blocking IFN production, the roles of the SAP domain during FMDV infection in host cells remain unknown. Therefore, we identified host proteins associated with the SAP domain of L(pro) by a high-throughput quantitative proteomic approach [isobaric tags for relative and absolute quantitation (iTRAQ) in conjunction with liquid chromatography/electrospray ionization tandem mass spectrometry]. Comparison of the differentially regulated proteins in rA/FMDVDeltamSAP- versus rA/FMDV-infected SK6 cells revealed 45 down-regulated and 32 up-regulated proteins that were mostly associated with metabolic, ribosome, spliceosome, and ubiquitin-proteasome pathways. The results also imply that the SAP domain has a function similar to SAF-A/B besides its potential protein inhibitor of activated signal transducer and activator of transcription (PIAS) function. One of the identified proteins UBE1 was further analyzed and displayed a novel role for the SAP domain of L(pro). Overexpression of UBE1 enhanced the replication of FMDV, and knockdown of UBE1 decreased FMDV replication. This shows that FMDV manipulates UBE1 for increased viral replication, and the SAP domain was involved in this process. PMID- 26354184 TI - From Vesalius to tractography. AB - The description of an anatomical specimen may look straightforward, but it appears that it depends in fact on several intermingled factors: technical methods for conservation, dissection and vascular injection and the anatomist skills are of course important. This is especially true when the studied organ, as for instance the brain, is subject to rapid putrefaction after death without any preservation technique. Nevertheless the possibility to reject, or at least criticize, the dominant paradigm is probably as important as these technical considerations: important changes occurred in brain representation between the early Middle Ages and the Early Modern Times, without major improvements of cadaveric preservation or dissection methods; Vesalius rejected the existence of the rete mirabile in human not only because he was a talented anatomist but also because he accepted and had the courage to fight the dominant tradition inherited from Galen. Such difficulties in the scientific approach obviously remain vivid, and should not be forgotten despite the development of modern tools for studying brain morphology and function. PMID- 26354185 TI - A longitudinal study of changes in Diffusion Tensor Value and their association with cognitive sequelae among patients with mild head injury. AB - BACKGROUND: Diffusion tensor imaging (DTI) is an advanced and sensitive technique that detects sub-threshold pathology in normal imaging brain injury patients. Currently, there are no longitudinal DTI studies to look for time-based changes. The present study has investigated longitudinal imaging and its association with cognitive deficits. METHODS: Twenty-one patients were available for MRI and neuropsychological test (NPT) assessment for all the 3 time points. Initially (<36 hours), all patients presented with GCS 15 and normal scan findings. The DTI (P<0.0001) and NPT scores (P<0.05) were analyzed using repeated-measure of analysis. The tensor values were correlated with specific time-point NPT scores using partial correlation (0.05). RESULTS: Right cerebral-hemisphere showed significant alterations in both anisotropy and diffusivity values overtime. Cingulate gyrus and occipital lobe showed prominent changes in anisotropy value. Significant improvement in thalamo-cortical anisotropy value after 3-4 months after injury was seen. The changes in diffusivity values were mainly seen in frontal, parietal lobe, right inferior fronto-occipital and superior longitudinal fasciculus, and posterior supramarginal gyrus. Time-related changes of tensor values of thalamus, frontal and temporal lobe had persistent and significant association with attention and learning/memory aspects. CONCLUSIONS: The findings of this study suggest that DTI detects and observes natural-recovery of brain regions affected by sub-threshold force. PMID- 26354186 TI - A review and update on the guidelines for the acute management of cervical spinal cord injury - Part II. AB - Acute traumatic spinal cord injury (SCI) is a debilitating worldwide disease with an estimated annual incidence of 10 to 83 affected individuals per million inhabitants. These injuries typically impact younger individuals and reduce quality-adjusted life years with estimated lifetime costs exceeding $4 million per person. Hence it is critical to establish and refine clear practice guidelines for acute management of SCI. In 2013 the Joint Section on Disorders of the Spine and Peripheral Nerves of the American Association of Neurological Surgeons (AANS) and the Congress of Neurological Surgeons (CNS) released a revision of the 2002 guidelines for Cervical SCI. In the present report we explore seven subsections for management of specific cervical injury types, review key supporting literature, and provide an update on recent studies since the publication of the 2013 guidelines. Our review finds a paucity of Level I and Level II treatment recommendations for cervical spine injuries, with the exception of subaxial cervical spine injury classification and surgical management for Type II odontoid fractures in the elderly. We recommend the systematic implementation of large randomized controlled studies across diverse demographics and ethnicities, injury mechanisms and morphologies to address pressing limitations in the current literature. The cohesive effort to adopt the 2013 AANS/CNS Guidelines and the National Institutes of Health (NIH)/National Institute of Neurological Disorders and Stroke (NINDS) Common Data Elements for SCI as part of a multicenter international approach will enable reproducible data collection and robust analyses toward achieving this goal. PMID- 26354187 TI - Surgical and endovascular treatment of poor-grade aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis. AB - INTRODUCTION: Poor-grade aneurysmal subarachnoid hemorrhage (aSAH) is associated with high morbidity and mortality. We evaluated trends in outcomes and treatment of poor-grade aSAH and performed a meta-analysis evaluating outcomes by treatment modality. EVIDENCE ACQUISITION: We performed a literature search for studies on surgical and endovascular treatment of poor-grade aSAH. We performed a random effects meta-analysis evaluating long-term good neurological outcome, long-term poor neurological outcome and mortality, comparing rates between endovascular and surgical treatments. We performed a subgroup analysis of outcome by treatment timing relative to the aSAH separating treatment timing into three categories: 1) ultra-early (within 48 hours of aSAH); 2) early (between 48 hours-1 week post aSAH); and 3) delayed (>1 week post-aSAH). We also evaluated trends in treatment modalities and good neurological outcome. EVIDENCE SYNTHESIS: Eighty-five non comparative studies with 4506 patients with poor-grade aSAH were included. The proportion of patients receiving endovascular treatment increased from 10.0% to 62.0% between 1990-2000 and 2010-2014. The rate of good neurological outcome increased from 37.0% to 44.0% over this time period. Long-term good neurological outcome was 38% (95% CI=33-43%) in the endovascular group and 39% (95% CI=34-44%) in the surgical group (P=0.74). Mortality rates were higher in the endovascular group compared to the surgical group (41% versus 31%, P=0.01). Overall, patients receiving ultra-early treatment had the highest rates of good neurological outcome (61% compared to 40% for early and 47% for delayed, P<0.01). CONCLUSIONS: Good neurological outcome rates are similar between surgery and endovascular treatment of poor grade aSAH. Ultra-early treatment is associated with improved clinical outcomes. PMID- 26354188 TI - Association between imaging findings and microbiological findings for image guided biopsies for spine infections. AB - BACKGROUND: In the evaluation of spondylodiscitis, a number of factors are thought to contribute to the positive-predictive-value of spine biopsy including biopsy technique and equipment, number of sample obtained, timing of antibiotics, imaging findings and lab values. The purpose of this study was to examine which technical, magnetic resonance imaging (MRI), laboratory and clinical findings are most frequently associated with positive cultures or histopathology among patients receiving spine biopsies with a focus on the association of imaging findings and positive cultures/histopathology. METHODS: Following International Review Board approval, we retrospectively reviewed a consecutive series of spine biopsies performed at our institution over a 28-month period in patients who received spine biopsies for radiographically and clinically suspicious spondylodiscitis. All patients underwent MRI prior to biopsy. Patient charts were reviewed for the following data: erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and white blood cell level at the time of biopsy, prior back surgeries, timing of last dose of antibiotics prior to biopsy, and length of antibiotic therapy prior to biopsy. We also reviewed procedure notes from the biopsy and collected the following data: technique (transpedicular versus parapedicular), equipment used, type of imaging guidance (CT versus fluoroscopy) and number of samples obtained. MRI studies were evaluated by two radiologists and rated on an ordinal 1-4 scale based on increasing suspicion for spondylodiscitis (1 lowest, 4 highest). All categorical variables were compared using chi-squared tests. All continuous variables were compared using Student's t tests. RESULTS: Seventy-seven patients are included in this study. Overall, 62% (48/77) were positive for infection on pathological and/or microbiological studies. There was a significant association between radiological index of suspicion and biopsy positivity as 0% (0/3) with index of 1, 31% (4/13) with an index of 2, 59% (10/17) with an index of 3 and 83% (30/36) with an index of 4 had positive pathology (P=0.001). Biopsy approach, type of imaging guidance, CBC, and number of passes were not associated with biopsy positivity. Elevated CRP was associated with biopsy positivity (P=0.002) while elevated ESR was not (P=0.12). On multivariate analysis adjusting for the MRI scale, ESR and CRP, increasing degree of suspicion on MRI was independently associated with biopsy positivity (P<0.01) while CRP and ESR were not independently associated with biopsy positivity. CONCLUSIONS: In this study of 77 patients receiving spinal biopsy for diagnosis of spondylodiscitis, a high index of suspicion based on MRI imaging was strongly associated with positive biopsy samples on culture and/or histopathology. In addition, imaging findings were independently associated with positive biopsy findings while elevated CRP and ESR were not. These findings suggest that MRI findings should be used to guide practitioners in their pursuit of a causative organism among patients with suspected discitis-osteomyelitis. PMID- 26354189 TI - The Evaluation of a Regional Faith Community Network's Million Hearts Program. AB - OBJECTIVE: The goal of the Million Hearts initiative is to prevent one million heart attacks and strokes by 2017. Maryland was one state in the Association of State and Territorial Health Official's Million Hearts State Learning Collaborative. Washington County, Maryland formed a collaboration between the County Health Department, Meritus Health System, and the Meritus Health Parish Nurse Coordinator to address hypertension in the county. PROGRAM PLAN AND IMPLEMENTATION: Within a regional network of 52 faith communities, the Parish Nurse Coordinator recruited 25 faith community nurses to participate in a three month program. Nurses were trained on proper blood pressure measurement and 22 nurses identified 58 participants engaged in blood pressure self-monitoring and coaching for lifestyle changes. Additionally, nurses took 1,729 blood pressures and provided health education to individuals within their congregations. PROGRAM EVALUATION: Fifty-one participants participated in blood pressure self-monitoring and lifestyle coaching with faith community nurses. There was improvement in six out of seven lifestyle areas. Eight-two percent of participants (N = 42) decreased their systolic and/or diastolic blood pressure over three months. CONCLUSION: Coaching provided by faith community nurses can create an environment of sustained support to promote improved lifestyle and blood pressure changes over time. PMID- 26354190 TI - Aeromicrobium camelliae sp. nov., isolated from Pu'er tea. AB - A novel Gram-reaction-positive, aerobic and non-spore-forming rod-shaped bacterial strain, YS17T, was isolated from ripened Pu'er tea. Growth of the strain was observed at 15-50 degrees C (optimum 30-37 degrees C) and at pH 5.5 10.5 (optimum 6.0-9.5). Phylogenetic analysis of 16S rRNA gene sequences indicated that the strain represented a member of the genus Aeromicrobium. The strains most closely related to YS17T were Aeromicrobium erythreum DSM 8599T, Aeromicrobium alkaliterrae JCM 13518T and Aeromicrobium ginsengisoli JCM 14732T, with 16S rRNA gene sequence similarities of 96.8, 96.8 and 96.7 %, respectively. DNA-DNA hybridization of YS17T with the type strains of the most closely related species, A. erythreum DSM 8599T, A. alkaliterrae JCM 13518T and A. ginsengisoli JCM 14732T, yielded reassociation values of 10.9, 16.8 and 10.9 %, respectively. The diagnostic diamino acid of the cell wall peptidoglycan was ll-diaminopimelic acid. The predominant menaquinones were menaquinone MK-9(H4) (76 %) and MK-8(H4) (17 %). The major fatty acids were C16 : 0, 10-methyl C18 : 0 and C18 : 1omega9c. The DNA G+C content of YS17T was 66 mol%. YS17T could be differentiated from recognized species of the genus Aeromicrobium on the basis of phenotypic characteristics, chemotaxonomic differences, phylogenetic analysis and DNA-DNA hybridization data. On the basis of evidence from the polyphasic analyses performed as part of this study a novel species, Aeromicrobium camelliae sp. nov., is proposed, with strain YS17T ( = CGMCC 1.12942T = JCM 30952T) as the type strain. PMID- 26354191 TI - Expert Surgeons Can Be Distinguished From Trainees, and Surgical Proficiency Can Be Defined, Using Validated Metrics and Shoulder Models. AB - Experts at performing arthroscopic shoulder Bankart procedures can be distinguished from surgical trainees using validated metrics and a cadaveric or simulator model. The combination of performance metrics plus models generates a tool that can be used to precisely and accurately define a performance threshold and assess whether or not a surgeon is proficient at performing a procedure. A tool that can be used to judge surgical expertise has implications for training and credentialing. Experienced surgeons make fewer mistakes and are faster than novices. PMID- 26354192 TI - Regarding "Delaying Surgery for Rotator Cuff Tears With Concomitant Stiffness". PMID- 26354193 TI - Authors' Reply. PMID- 26354194 TI - Pre- and Postseason Dynamic Ultrasound Evaluation of the Pitching Elbow. AB - PURPOSE: To use ultrasound imaging to document changes over time (i.e., preseason v postseason) in the pitching elbow of high school baseball pitchers. METHODS: Twenty-two high school pitchers were prospectively followed. Pitchers were evaluated after a 2-month period of relative arm rest via preseason physical exams, dynamic ultrasound imaging of their throwing elbow, and the Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) assessment. Players were reevaluated within 1 week of their last game. Dynamic ultrasound images were then randomized, blinded to testing time point, and evaluated by 2 fellowship-trained musculoskeletal radiologists. RESULTS: Average pitcher age was 16.9 years. Average pitches thrown was 456.5, maximum velocity 77.7 mph, games pitched 7.3, and days off between starts 6.6. From preseason to postseason, there were significant increases in ulnar collateral ligament (UCL) thickness (P = .02), ulnar nerve cross-sectional area (P = .001), UCL substance heterogeneity (P = .001), and QuickDASH scores (P = .03). In addition, there was a nonsignificant increase in loaded ulnohumeral joint space (P = .10). No pitchers had loose bodies on preseason exam, while 3 demonstrated loose bodies postseason. The increase in UCL thickness was significantly associated with the number of bullpen sessions per week (P = .01). The increase in ulnar nerve cross-sectional area was significantly associated with the number of pitches (P = .04), innings pitched (P = .01), and games pitched (P = .04). CONCLUSIONS: The stresses placed on the elbow during only one season of pitching create adaptive changes to multiple structures about the elbow including UCL heterogeneity and thickening, increased ulnohumeral joint space laxity, and enlarged ulnar nerve cross-sectional area. LEVEL OF EVIDENCE: Level II prospective observational study. PMID- 26354195 TI - Editorial Commentary: Editor's Conflict of Interest. AB - The Editor-in-chief has recused himself from industry consulting, which he performed before assuming the position, and returned related royalties and divested related stock options, in order to mitigate against conflict-of interest. The Editor discloses affiliation with an institution that receives support from diverse industry partners in support of research and education. PMID- 26354196 TI - Outcome of Single-Bundle Hamstring Anterior Cruciate Ligament Reconstruction Using the Anteromedial Versus the Transtibial Technique: A Systematic Review and Meta-analysis. AB - PURPOSE: To compare the clinical outcomes of single-bundle hamstring anterior cruciate ligament (ACL) reconstruction between the anteromedial (AM) and transtibial (TT) techniques. METHODS: We performed a comprehensive systematic review and meta-analysis of the English-language literature in the PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials databases for articles that compared clinical outcomes of AM versus TT ACL reconstruction. The outcome measures analyzed included postoperative Lachman test, pivot-shift test, International Knee Documentation Committee (IKDC), and Lysholm scores. RESULTS: We included 10 articles from an initial 308 abstracts for the systematic review and included 6 studies for the meta-analysis. The study population consisted of a total of 733 patients, of whom 366 (49.9%) underwent the AM technique and 367 (50.1%) underwent the TT technique for ACL reconstruction. For postoperative knee stability, the AM technique yielded superior results in terms of the proportion of negative Lachman test results (n = 243; odds ratio [OR], 2.98 [95% confidence interval (CI), 1.29 to 6.88]) and proportion of negative pivot-shift test results (n = 238; OR, 3.67 [95% CI, 1.80 to 7.52]). For postoperative functional status, the AM technique yielded superior results in terms of objective IKDC grading (proportion with IKDC grade A) (n = 269; OR, 2.19 [95% CI, 1.23 to 3.88]) but had comparable Lysholm scores (n = 478; mean difference, 1.43 [95% CI, 0.01 to 2.84]). CONCLUSIONS: Single-bundle hamstring ACL reconstruction using the AM technique showed superior surgeon recorded stability according to the IKDC knee score, Lachman test, and pivot shift test. However, there was no difference in patient-reported functional outcome (Lysholm score). LEVEL OF EVIDENCE: Level III, systematic review and meta analysis of Level I, II, and III studies. PMID- 26354197 TI - Editorial Commentary: Average and Below-Average Surgeons May Struggle With the Anteromedial Portal Technique for Creating the Anterior Cruciate Ligament Femoral Socket. AB - Average surgeons may struggle with the anteromedial (AM) portal technique for creating the anterior cruciate ligament femoral socket. The AM portal technique is technically challenging. The AM portal technique demonstrates better surgeon recorded stability than the transtibial technique, but no clinical differences according to a review of published, comparative research studies. PMID- 26354198 TI - Editorial Commentary: Posterior Cruciate Ligament Remnant Preservation Has Hypothetical Advantages. AB - Posterior cruciate ligament (PCL) remnant preservation has hypothetical advantages, but studies directly comparing PCL reconstruction with or without remnant preservation are not identified. PMID- 26354199 TI - Editorial Commentary: Meniscal Root Avulsion Repair Outcomes Are at the Level of a Salvage Procedure. AB - Indications for meniscal root avulsion repair require refinement because current results show failure or extrusion in more than one-third of patients, and long term follow-up is required before concluding that saving the meniscus results in osteoarthritis prevention. PMID- 26354200 TI - Editorial Commentary: Tibial Tubercle Osteotomy Complications Are Most Common With Complete Detachment of the Distal Periosteal Hinge. AB - Tibial tubercle osteotomy (TTO) is complex because flat osteotomy is indicated for instability whereas anteromedialization is indicated for osteoarthritis. Instability is associated with patella alta, which sometimes requires distalization, and sometimes pediatric considerations include incompletely ossified tibial tubercle and open growth plates. Complete detachment, as is required for distalization, results in the highest rate of complications after TTO. PMID- 26354201 TI - Editorial Commentary: Osteochondral Allograft of the Humeral Head. AB - Despite reports of significant improvement in some patients, osteochondral allograft of the humeral head could be considered a procedure of last resort. PMID- 26354202 TI - Umbilical Cord Tissue Offers the Greatest Number of Harvestable Mesenchymal Stem Cells for Research and Clinical Application: A Literature Review of Different Harvest Sites. AB - PURPOSE: Recent years have seen dramatic increases in the techniques used to harvest and isolate human mesenchymal stem cells. As the potential therapeutic aspects of these cells further develop, informative data on the differences in yields between tissue harvest sites and methods will become increasingly valuable. We collected and compared data on cell yields from multiple tissue harvest sites to provide insight into the varying levels of mesenchymal stem cells by tissue and offer primary and alternative tissue types for harvest and clinical application. METHODS: The PubMed and Medline databases were searched for articles relating to the harvest, isolation, and quantification of human mesenchymal stem cells. Selected articles were analyzed for relevant data, which were categorized according to tissue site and, if possible, standardized to facilitate comparison between sites. RESULTS: Human mesenchymal stem cell levels in tissue varied widely according to tissue site and harvest method. Yields for adipose tissue ranged from 4,737 cells/mL of tissue to 1,550,000 cells/mL of tissue. Yields for bone marrow ranged from 1 to 30 cells/mL to 317,400 cells/mL. Yields for umbilical cord tissue ranged from 10,000 cells/mL to 4,700,000 cells/cm of umbilical cord. Secondary tissue harvest sites such as placental tissue and synovium yielded results ranging from 1,000 cells/mL to 30,000 cells/mL. CONCLUSIONS: Variations in allogeneic mesenchymal stem cell harvest levels from human tissues reflect the evolving nature of the field, patient demographic characteristics, and differences in harvest and isolation techniques. At present, Wharton's jelly tissue yields the highest concentration of allogeneic mesenchymal stem cells whereas adipose tissue yields the highest levels of autologous mesenchymal stem cells per milliliter of tissue. CLINICAL RELEVANCE: This comparison of stem cell levels from the literature offers a primer and guide for harvesting mesenchymal stem cells. Larger mesenchymal stem cell yields are more desirable for research and clinical application. PMID- 26354203 TI - Editorial Commentary: Stem Cell Research in Arthroscopy Is Scant and Requires Basic Science Review. AB - Stem cell research in Arthroscopy is rare, but review of journals beyond orthopaedics yields many interesting highlights. The key points are that sources of stem cells vary with regard to cellular yield, but manipulation to improve the yield is severely limited by the United States Food and Drug Administration. PMID- 26354204 TI - A meta-analysis of the validity of FFQ targeted to adolescents. AB - OBJECTIVE: The present work is aimed at meta-analysing validity studies of FFQ for adolescents, to investigate their overall accuracy and variables that can affect it negatively. DESIGN: A meta-analysis of sixteen original articles was performed within the ASSO Project (Adolescents and Surveillance System in the Obesity prevention). SETTING: The articles assessed the validity of FFQ for adolescents, compared with food records or 24 h recalls, with regard to energy and nutrient intakes. SUBJECTS: Pearson's or Spearman's correlation coefficients, means/standard deviations, kappa agreement, percentiles and mean differences/limits of agreement (Bland-Altman method) were extracted. Pooled estimates were calculated and heterogeneity tested for correlation coefficients and means/standard deviations. A subgroup analysis assessed variables influencing FFQ accuracy. RESULTS: An overall fair/high correlation between FFQ and reference method was found; a good agreement, measured through the intake mean comparison for all nutrients except sugar, carotene and K, was observed. Kappa values showed fair/moderate agreement; an overall good ability to rank adolescents according to energy and nutrient intakes was evidenced by data of percentiles; absolute validity was not confirmed by mean differences/limits of agreement. Interviewer administration mode, consumption interval of the previous year/6 months and high number of food items are major contributors to heterogeneity and thus can reduce FFQ accuracy. CONCLUSIONS: The meta-analysis shows that FFQ are accurate tools for collecting data and could be used for ranking adolescents in terms of energy and nutrient intakes. It suggests how the design and the validation of a new FFQ should be addressed. PMID- 26354205 TI - MERS may not be SARS; but India is still vulnerable. PMID- 26354206 TI - Obesity paradigm in India: Are the consequences an impending Tsunami? PMID- 26354207 TI - Evaluating the performance of health promotion interventions. PMID- 26354208 TI - Oxidative stress, thyroid dysfunction & Down syndrome. AB - Down syndrome (DS) is one of the most common chromosomal disorders, occurring in one out of 700-1000 live births, and the most common cause of mental retardation. Thyroid dysfunction is the most typical endocrine abnormality in patients with DS. It is well known that thyroid dysfunction is highly prevalent in children and adults with DS and that both hypothyroidism and hyperthyroidism are more common in patients with DS than in the general population. Increasing evidence has shown that DS individuals are under unusual increased oxidative stress, which may be involved in the higher prevalence and severity of a number of pathologies associated with the syndrome, as well as the accelerated ageing observed in these individuals. The gene for Cu/Zn superoxide dismutase (SOD1) is coded on chromosome 21 and it is overexpressed (~50%) resulting in an increase of reactive oxygen species (ROS) due to overproduction of hydrogen peroxide (H 2 O 2 ). ROS leads to oxidative damage of DNA, proteins and lipids, therefore, oxidative stress may play an important role in the pathogenesis of DS. PMID- 26354209 TI - Systematic review of drug utilization studies & the use of the drug classification system in the WHO-SEARO Region. AB - BACKGROUND & OBJECTIVES: Information available on drug consumption is inadequate in most low and middle income countries. This systematic review was conducted to analyse published work on drug utilization research/studies (DUR) in the SEARO region of WHO for study objectives, methodology, results and recommendations and to identify the need for improving DUR and the use of the ATC/DDD system. METHODS: A literature search for DUR was carried out in biomedical databases (PubMed, Scirus, Scopus and Google Scholar) up to May 2012. Publications were selected if those were in the English language, describing DUR or prescription practices, and study conducted in the WHO-SEARO countries. RESULTS: A total of 318 publications were included in the review. Of these, 67 per cent were from India and 13 per cent were from Thailand. Majority of the publications were hospital based; only 16 per cent were community based. The ATC/DDD system was used in only 20 per cent of the publications, of which 73 per cent publications used DDD indicators. Several publications focused on antibiotics (31%). Publications that recommended the need for a policy or intervention to improve prescription practices/rational drug use amounted to 35 per cent. INTERPRETATION & CONCLUSIONS: Drug utilization studies using ATC/DDD system need to be promoted and carried out on an ongoing basis. DUR is important for rational use of drugs. Its relevance to policy making and resource allocation needs to be emphasized. PMID- 26354210 TI - Antimicrobial stewardship programme (AMSP) practices in India. AB - A survey was conducted to ascertain practice of antimicrobial stewardship programme (AMSP) in India for 2013. A total of 20 health care institutions (HCI) responded to a detailed questionnaire. All the institutions contacted were tertiary care HCI, of which 12 were funded by government (GHCI) and 8 were corporate/private HCI (PHCI). Further, all catered to both rural and urban populations and were spread across the country. Written documents were available with 40 per cent for AMSP, 75 per cent for hospital infection control (HIC) and HIC guidelines and 65 per cent for antimicrobial agents (AMA) prescription guidelines. Records were maintained for health care associated infections (HCAI) by 60 per cent HCI. Antimicrobial resistance (AMR) data were being analysed by 80 per cent HCI. AMA usage data were analysed by only 25 per cent HCI and AMA prescription audit and feedback by 30 per cent. PHCI performed better than GHCI across all fields of AMSP. The main contributory factor was possibly the much higher level of accreditation of PHCI hospitals and their diagnostic laboratories. The absence of infectious diseases physicians and clinical pharmacists is worrying and demands careful attention. PMID- 26354212 TI - Mobilizing community-based health insurance to enhance awareness & prevention of airborne, vector-borne & waterborne diseases in rural India. AB - BACKGROUND & OBJECTIVES: Despite remarkable progress in airborne, vector-borne and waterborne diseases in India, the morbidity associated with these diseases is still high. Many of these diseases are controllable through awareness and preventive practice. This study was an attempt to evaluate the effectiveness of a preventive care awareness campaign in enhancing knowledge related with airborne, vector-borne and waterborne diseases, carried out in 2011 in three rural communities in India (Pratapgarh and Kanpur-Dehat in Uttar Pradesh and Vaishali in Bihar). METHODS: Data for this analysis were collected from two surveys, one done before the campaign and the other after it, each of 300 randomly selected households drawn from a larger sample of Self-Help Groups (SHGs) members invited to join community-based health insurance (CBHI) schemes. RESULTS: The results showed a significant increase both in awareness (34%, p<0.001) and in preventive practices (48%, P=0.001), suggesting that the awareness campaign was effective. However, average practice scores (0.31) were substantially lower than average awareness scores (0.47), even in post-campaign. Awareness and preventive practices were less prevalent in vector-borne diseases than in airborne and waterborne diseases. Education was positively associated with both awareness and practice scores. The awareness scores were positive and significant determinants of the practice scores, both in the pre- and in the post-campaign results. Affiliation to CBHI had significant positive influence on awareness and on practice scores in the post-campaign period. INTERPRETATION & CONCLUSIONS: The results suggest that well-crafted health educational campaigns can be effective in raising awareness and promoting health-enhancing practices in resource-poor settings. It also confirms that CBHI can serve as a platform to enhance awareness to risks of exposure to airborne, vector-borne and waterborne diseases, and encourage preventive practices. PMID- 26354211 TI - Prevalence of generalized & abdominal obesity in urban & rural India--the ICMR INDIAB Study (Phase-I) [ICMR- NDIAB-3]. AB - BACKGROUND & OBJECTIVES: Overweight and obesity are rapidly increasing in countries like India. This study was aimed at determining the prevalence of generalized, abdominal and combined obesity in urban and rural India. METHODS: Phase I of the ICMR-INDIAB study was conducted in a representative population of three States [Tamil Nadu (TN), Maharashtra (MH) and Jharkhand (JH)] and one Union Territory (UT)[Chandigarh (CH)] of India. A stratified multi-stage sampling design was adopted and individuals >= 20 yr of age were included. WHO Asia Pacific guidelines were used to define overweight [body mass index (BMI) >= 23 kg/m [2] but < 25 kg/m [2]], generalized obesity (GO, BMI >= 25 kg/m [2], abdominal obesity (AO, waist circumference >= 90 cm for men and >= 80 cm for women) and combined obesity (CO, GO plus AO). Of the 14,277 participants, 13,800 subjects (response rate, 96.7%) were included for the analysis (urban: n = 4,063; rural: n = 9737). RESULTS: The prevalence of GO was 24.6, 16.6, 11.8 and 31.3 per cent among residents of TN, MH, JH and CH, while the prevalence of AO was 26.6, 18.7, 16.9 and 36.1 per cent, respectively. CO was present in 19.3, 13.0, 9.8 and 26.6 per cent of the TN, MH, JH and CH population. The prevalence of GO, AO and CO were significantly higher among urban residents compared to rural residents in all the four regions studied. The prevalence of overweight was 15.2, 11.3, 7.8 and 15.9 per cent among residents of TN, MH, JH and CH, respectively. Multiple logistic regression analysis showed that female gender, hypertension, diabetes, higher socio-economic status, physical inactivity and urban residence were significantly associated with GO, AO and CO in all the four regions studied. Age was significantly associated with AO and CO, but not with GO. INTERPRETATION & CONCLUSIONS: Prevalence of AO as well as of GO were high in India. Extrapolated to the whole country, 135, 153 and 107 million individuals will have GO, AO and CO, respectively. However, these figures have been estimated from three States and one UT of India and the results may be viewed in this light. PMID- 26354213 TI - Efficacy of stem cell in improvement of left ventricular function in acute myocardial infarction--MI3 Trial. AB - BACKGROUND & OBJECTIVES: Acute myocardial infarction (AMI) is characterized by irreparable and irreversible loss of cardiac myocytes. Despite major advances in the management of AMI, a large number of patients are left with reduced left ventricular ejection fraction (LVEF), which is a major determinant of short and long term morbidity and mortality. A review of 33 randomized control trials has shown varying improvement in left ventricular (LV) function in patients receiving stem cells compared to standard medical therapy. Most trials had small sample size and were underpowered. This phase III prospective, open labelled, randomized multicenteric trial was undertaken to evaluate the efficacy in improving the LVEF over a period of six months, after injecting a predefined dose of 5-10 * 10 [8] autologous mononuclear cells (MNC) by intra-coronary route, in patients, one to three weeks post ST elevation AMI, in addition to the standard medical therapy. METHODS: In this phase III prospective, multicentric trial 250 patients with AMI were included and randomized into stem cell therapy (SCT) and non SCT groups. All patients were followed up for six months. Patients with AMI having left ventricular ejection fraction (LVEF) of 20-50 per cent were included and were randomized to receive intracoronary stem cell infusion after successfully completing percutaneous coronary intervention (PCI). RESULTS: On intention-to treat analysis the infusion of MNCs had no positive impact on LVEF improvement of >= 5 per cent. The improvement in LVEF after six months was 5.17 +/- 8.90 per cent in non SCT group and 4.82 +/- 10.32 per cent in SCT group. The adverse effects were comparable in both the groups. On post hoc analysis it was noted that the cell dose had a positive impact when infused in the dose of >= 5 X 10 [8] (n=71). This benefit was noted upto three weeks post AMI. There were 38 trial deviates in the SCT group which was a limitation of the study. INTERPRETATION & CONCLUSIONS: Infusion of stem cells was found to have no benefit in ST elevation AMI. However, the procedure was safe. A possible benefit was seen when the predefined cell dose was administered which was noted upto three weeks post AMI, but this was not significant and needs confirmation by larger trials. PMID- 26354215 TI - Equity in utilization of health care services: Perspective of pregnant women in southern Odisha, India. AB - BACKGROUND & OBJECTIVES: Inequity in the use of health care services is an important factor affecting the maternal and child survival. In southern Odisha, India, the health indicators remained below compared to the State and national average. This study identifies various equity issues at individual and community levels that influence women's choice affecting the utilization of maternal health services in a district in southern Odisha. METHODS: A qualitative study was carried out in Gajam district, rural region of south Odisha. Ten in-depth interviews were carried out till data saturation with women having less than one year child and 10 focus group discussions with the average eight women in each group having less than five year old child, community and health care providers separately. A total of 120 respondents were included in the study using in-depth interview and focus group discussions. RESULTS: The important determinants in utilization of health care services by women emerging from the study were transportation and financial constraints. In addition, it was found that divergent aetiological concepts and low perceived hospital benefits of the women and community were equally important determinants. Further, community had different perceptions and interpretations of danger signs influencing the risk approach and health care seeking behaviour. INTERPRETATION & CONCLUSIONS: Our findings show that to increase the utilization of health care services, the grass root health workers should be made aware of specific social determinants of risk, perceptions and preferences. m0 ore attention should be given to the transportation system, and its operational feasibility. The husband of the women and the elders of the family should be considered as an important unit of interjection. A more individualized antenatal consultation could be provided by taking into account women's perception of risk and their explanatory models. PMID- 26354214 TI - Molecular response to imatinib & its correlation with mRNA expression levels of imatinib influx & efflux transporters in patients with chronic myeloid leukaemia in chronic phase. AB - BACKGROUND & OBJECTIVES: Imatinib is the standard first-line treatment for chronic myeloid leukaemia (CML) patients. About 20 to 30 per cent patients develop resistance to imatinib and fail imatinib treatment. One of the mechanisms proposed is varying expression levels of the drug transporters. This study was aimed to determine the expression levels of imatinib transporter genes (OCT1, ABCB1, ABCG2) in CML patients and to correlate these levels with molecular response. METHODS: Sixty three CML chronic phase patients who were on 400 mg/day imatinib for more than two years were considered for gene expression analysis study for OCT1, ABCB1 and ABCG2 genes. These were divided into responders and non responders. The relative transcript expression levels of the three genes were compared between these two categories. The association between the expression values of these three genes was also determined. RESULTS: No significant difference in the expression levels of OCT1, ABCB1 and ABCG2 was found between the two categories. The median transcript expression levels of OCT1, ABCB1 and ABCG2 genes in responders were 26.54, 10.78 and 0.64 versus 33.48, 7.09 and 0.53 in non-responders, respectively. A positive association was observed between the expression of the ABCB1 and ABCG2 transporter genes (r=0.407, P<0.05) while no association was observed between the expression of either of the ABC transporter genes with the OCT1 gene. INTERPRETATION & CONCLUSIONS: Our findings demonstrated that the mRNA expression levels of imatinib transporter genes were not correlated with molecular response in CML patients. Further studies need to be done on a large sample of CML patients to confirm these findings. PMID- 26354216 TI - A novel antagonistic role of natural compound icariin on neurotoxicity of amyloid beta peptide. AB - BACKGROUND & OBJECTIVES: Amyloid beta-peptide (Abeta) has been shown to be responsible for senile plaque formation and cell damage in Alzheimer's disease (AD). This study was aimed to explore the role of natural compound icariin on the aggregation and the cytotoxicity of Abeta in vitro. METHODS: Thioflavin T (ThT) fluorescence assay and transmission electron microscopy (TEM) imaging were done to determine the influence of icariin on the aggregation of Abeta1-42 peptide. MTT assay was used to evaluate the protective effect of icariin on Abeta1-42 induced cytotoxicity in neuroblastoma SH-SY5Y cells. RESULTS: Icariin inhibited Abeta1-42 aggregation in a dose-dependent manner. Additionally, icariin also prevented the cytotoxicity of Abeta1-42 in SH-SY5Y cells by decreasing the production of peroxide hydrogen during the aggregation of this peptide. INTERPRETATION & CONCLUSIONS: The results indicated a novel antagonistic role of icariin in the neurotoxicity of Abeta1-42 via inhibiting its aggregation, suggesting that icariin might have potential therapeutic benefits to delay or modify the progression of AD. PMID- 26354217 TI - Development & validation of a quantitative anti-protective antigen IgG enzyme linked immunosorbent assay for serodiagnosis of cutaneous anthrax. AB - BACKGROUND & OBJECTIVES: Anthrax caused by Bacillus anthracis is primarily a disease of herbivorous animals, although several mammals are vulnerable to it. ELISA is the most widely accepted serodiagnostic assay for large scale surveillance of cutaneous anthrax. The aims of this study were to develop and evaluate a quantitative ELISA for determination of IgG antibodies against B. anthracis protective antigen (PA) in human cutaneous anthrax cases. METHODS: Quantitative ELISA was developed using the recombinant PA for coating and standard reference serum AVR801 for quantification. A total of 116 human test and control serum samples were used in the study. The assay was evaluated for its precision, accuracy and linearity. RESULTS: The minimum detection limit and lower limit of quantification of the assay for anti-PA IgG were 3.2 and 4 ug/ml, respectively. The serum samples collected from the anthrax infected patients were found to have anti-PA IgG concentrations of 5.2 to 166.3 ug/ml. The intra-assay precision per cent CV within an assay and within an operator ranged from 0.99 to 7.4 per cent and 1.7 to 3.9 per cent, respectively. The accuracy of the assay was high with a per cent error of 6.5 - 24.1 per cent. The described assay was found to be linear between the range of 4 to 80 ng/ml (R [2] = 0.9982; slope = 0.9186; intercept = 0.1108). INTERPRETATION & CONCLUSIONS: The results suggested that the developed assay could be a useful tool for quantification of anti-PA IgG response in human after anthrax infection or vaccination. PMID- 26354218 TI - Detection of Wolbachia from field collected Aedes albopictus Skuse in Malaysia. AB - BACKGROUND & OBJECTIVES: Wolbachia-based vector control strategies have been proposed as a mean to augment the existing measures for controlling dengue vector. Prior to utilizing Wolbachia in novel vector control strategies, it is crucial to understand the Wolbachia-mosquito interactions. Many studies have only focused on the prevalence of Wolbachia in female Aedes albopictus with lack of attention on Wolbachia infection on the male Ae. albopictus which also affects the effective expression of Wolbachia induced- cytoplasmic incompatibility (CI). In this study, field surveys were conducted to screen for the infection status of Wolbachia in female and male Ae. albopictus from various habitats including housing areas, islands and seashore. METHODS: Adult Ae. albopictus (n=104) were collected using human landing catches and hand aspirator. Standard ovitraps were also set in the selected areas for five days and the larvae were identified to species level. All the collected Ae. albopictus were screened for the presence of Wolbachia using multiplex polymerase chain reaction (PCR) and gene sequencing of Wolbachia surface protein (wsp) gene. RESULTS: A 100 per cent positivity of Wolbachia infection was observed for individual Ae. albopictus screened. For pooled mosquitoes, 73 of the 76 pools (female) and 83 of the 87 pools (male) were positive with Wolbachia infection. The wsp gene sequence of the Wolbachia strain isolated from individual and pooled mosquitoes showed a 100 per cent homology with Wolbachia sp. of Ae. albopictus isolated from various geographical regions. Phylogenetic analysis based on wsp gene fragments showed that the isolates were clustered into groups A and B, respectively. INTERPRETATION & CONCLUSIONS: The results indicated that Wolbachia infection was widespread in Ae. albopictus population both in female and male Ae. albopictus. All the infected females were superinfected with both A and B strains while the infected males showed a combination of superinfection of A and B strains and single infection of B strain. PMID- 26354219 TI - Insecticide susceptibility of Phlebotomus argentipes & assessment of vector control in two districts of West Bengal, India. AB - BACKGROUND & OBJECTIVES: Kala-azar or visceral leishmanisis (VL) is known to be endemic in several States of India including West Bengal (WB). Only meager information is available on the vector dynamics of its vector species, Phlebotomus argentipes particularly in relation to control measure from this State. Hence, a pilot study was undertaken to assess the control strategy and its impact on vector in two endemic districts of WB, India. METHODS: Two villages each from the two districts, Maldah and Burdwan, were selected for the study. Seasonal variation of sandflies was observed during pre-monsoon, post-monsoon and winter seasons. Susceptibility test of P. argentipes against DDT and bioassay on DDT sprayed wall and on long lasting insecticide nets (LN) Perma Net [(r)] 2.0 were conducted as per the WHO standard methods. RESULTS: P. argentipes density was high during March to October. Susceptibility status of P. argentipes ranged from 40 to 61.54 per cent. Bioassay test showed 57.89 per cent mortality against LN PermaNet [(r)] -2.0. and 50 per cent against DDT on wall within 30 min of exposure. INTERPRETATION & CONCLUSIONS: Despite the integrated vector management approach, the sandfly population was high in the study area. The reason could be development of resistance in P. argentipes against DDT and low effectiveness of LN PermaNet [(r)] -2.0. The more pragmatic step will be to conduct large studies to monitor the susceptibility level in P. argentipes against DDT. PMID- 26354220 TI - Prescription practices & use of essential medicines in the primary health care system, Shimoga district, Karnataka, India. PMID- 26354221 TI - Exome sequencing & homozygosity mapping for identification of genetic aetiology for spastic ataxia in a consanguineous family. PMID- 26354222 TI - INOSA Guidelines in the era of precision medicine. PMID- 26354223 TI - Mucocutaneous blisters & a mediastinal mass: Lifesaving role of surgery. PMID- 26354224 TI - Herpetic cheilitis. PMID- 26354225 TI - SUMO-regulated transcription: challenging the dogma. AB - The small ubiquitin-like modifier SUMO regulates many aspects of cellular physiology to maintain cell homeostasis, both under normal conditions and during cell stress. Components of the transcriptional apparatus and chromatin are among the most prominent SUMO substrates. The prevailing view is that SUMO serves to repress transcription. However, as we will discuss in this review, this model needs to be refined, because recent studies have revealed that SUMO can also have profound positive effects on transcription. PMID- 26354226 TI - Editorial: Design and Development of New Chemoinformatics Tools for Virtual Screening. PMID- 26354227 TI - Interactions of several genetic polymorphisms and alcohol consumption on blood pressure levels. AB - This study aimed to detect the interactions of several single nucleotide polymorphisms (SNPs) and alcohol consumption on blood pressure levels. Genotypes of 10 SNPs in the ATP-binding cassette transporter A1 (ABCA-1), acyl CoA:cholesterol acyltransferase-1 (ACAT-1), low density lipoprotein receptor (LDLR), hepatic lipase gene (LIPC), endothelial lipase gene (LIPG), methylenetetrahydrofolate reductase (MTHFR), the E3 ubiquitin ligase myosin regulatory light chain-interacting protein (MYLIP), proprotein convertase subtilisin-like kexin type 9 (PCSK9), peroxisome proliferator-activated receptor delta (PPARD), and Scavenger receptor class B type 1 (SCARB1) genes were determined in 616 nondrinkers and 608 drinkers. The genotypic frequencies of LDLR rs5925, LIPC rs2070895, MTHFR rs1801133, and MYLIP rs3757354 SNPs were significantly different between nondrinkers and drinkers. The levels of systolic blood pressure (ABCA-1 rs2066715 and rs2070895), diastolic blood pressure (rs2070895), and pulse pressure (PP) (rs2066715, ACAT-1 rs1044925, and rs1801133) in nondrinkers, and systolic blood pressure (rs1044925 and SCARB1 rs5888), diastolic blood pressure (rs1044925 and LIPG rs2000813), and PP (PCSK9 rs505151 and rs5888) in drinkers were different among the genotypes (P < 0.005-0.001). The interactions of several SNPs and alcohol consumption on systolic blood pressure (rs2066715, rs1044925, rs5925, rs2070895, rs1801133, rs3757354, PPARD rs2016520, and rs5888), diastolic blood pressure (rs2066715, rs1044925, rs5925, rs2000813, rs3757354, and rs2016520), and PP (rs1044925, rs2070895, rs1801133, rs3757354, rs505151, and rs5888) were observed (P < 0.005-0.001). The differences in blood pressure levels between the nondrinkers and drinkers might be partially attributed to the interactions of these SNPs and alcohol consumption. PMID- 26354228 TI - Late complete atrioventricular block after closure of an atrial septal defect with a gore septal occluder (GSOTM). AB - Temporary intermittent complete heart block (CHB) occurred the day after interventional closure of an ASD with a 30 mm Gore Septal Occluder (GSOTM) in a 2 years and 11-month-old female. CHB disappeared without further treatment and stable sinus rhythm recovered within 3 days. Only short episodes of 2nd degree AV block (Wenckebach periodicity) at rare intervals were documented in Holter monitors the following 2 months. Eleven months after device implantation the patient suffered from long lasting episodes of CHB. Surgical removal of the device resulted in incomplete recovery of AV-conduction. Histopathological work up of the explanted GSO showed complete endothelialization of the device and regular scar formation. One year after surgery, the child had sinus rhythm during daytime but needed VVI-pacing while sleeping. Young age, inferior localization of the defect, and use of a large device have been individual risk factors for CHB in this patient. Clinical course and histologic findings indicate that mechanical compression was the only cause for CHB. The cumulative number of reports of CHB after use of different ASD-devices supports the recommendation to postpone the intervention in asymptomatic patients to preschool-age. Early removal of a pushing device may increase the chance of complete recovery from CHB. PMID- 26354230 TI - Validation of new real-time polymerase chain reaction assays for detection of hepatitis A virus RNA and parvovirus B19 DNA. AB - BACKGROUND: To meet European guidelines for plasma for fractionation, plasma fractionators have implemented parvovirus B19 (B19V) and hepatitis A virus (HAV) nucleic acid test (NAT) screening on test pools. In this study we evaluate recently developed in-house NAT assays for B19V DNA and HAV RNA. The B19V NAT was designed to target two different regions of the B19V genome. STUDY DESIGN AND METHODS: The B19V DNA and HAV RNA tests were validated according to commonly used guidelines. The performance of the B19V and HAV assays was evaluated during routine screening of more than 2 * 10(6) donations. RESULTS: The 95% lower limit of detection (LLD) of the HAV NAT was 1.34 IU/mL. The 95% LLD for B19V was 39.1 IU/mL for the NS1 region and 76.9 IU/mL for the VP2 region. The B19V test showed good accuracy, precision, robustness, and no cross-contamination was observed. Both assays detected B19V Genotypes 1 to 3 and HAV Genotypes I to III. During routine screening 103 donations showed B19V DNA loads of more than 1.25 * 10(6) IU/mL and one donation was reactive in the HAV NAT. CONCLUSION: The dual-target B19V polymerase chain reaction (PCR) showed good accuracy (<0.1 log IU/mL) at the crucial concentration of 10 IU/uL for the NS1 and the VP2 region of the B19V genome and detected all known genotypes with similar sensitivity for each genotype. In addition, the dual target format reduces the chance that molecular variants of B19V are wrongly quantified. The HAV RNA assay showed high sensitivity for Genotypes I to III. Both new PCR assays have been successfully introduced for plasma screening in test pools of 480 or 96 donations. PMID- 26354229 TI - Epigenetic regulation of Smad2 and Smad3 by profilin-2 promotes lung cancer growth and metastasis. AB - Altered transforming growth factor-beta (TGF-beta) signalling has been implicated in tumour development and progression. However, the molecular mechanism behind this alteration is poorly understood. Here we show that profilin-2 (Pfn2) increases Smad2 and Smad3 expression via an epigenetic mechanism, and that profilin-2 and Smad expression correlate with an unfavourable prognosis of lung cancer patients. Profilin-2 overexpression promotes, whereas profilin-2 knockdown drastically reduces, lung cancer growth and metastasis. We show that profilin-2 suppresses the recruitment of HDAC1 to Smad2 and Smad3 promoters by preventing nuclear translocation of HDAC1 through protein-protein interaction at the C terminus of both proteins, leading to the transcriptional activation of Smad2 and Smad3. Increased Smad2 and Smad3 expression enhances TGF-beta1-induced EMT and production of the angiogenic factors VEGF and CTGF. These findings reveal a new regulatory mechanism of TGF-beta1/Smad signalling, and suggest a potential molecular target for the development of anticancer drugs. PMID- 26354232 TI - Postoperative Acute Pulmonary Embolism Following Pulmonary Resections. AB - Postoperative acute pulmonary embolism after pulmonary resections is highly fatal complication. Many literatures have documented cancer to be the highest risk factor for acute pulmonary embolism after pulmonary resections. Early diagnosis of acute pulmonary embolism is highly recommended and computed tomographic pulmonary angiography is the gold standard in diagnosis of acute pulmonary embolism. Anticoagulants and thrombolytic therapy have shown a great success in treatment of acute pulmonary embolism. Surgical therapies (embolectomy and inferior vena cava filter replacement) proved to be lifesaving but many literatures favored medical therapy as the first choice. Prophylaxis pre and post operation is highly recommended, because there were statistical significant results in different studies which supported the use of prophylaxis in prevention of acute pulmonary embolism. Having reviewed satisfactory number of literatures, it is suggested that thoroughly preoperative assessment of patient conditions, determining their risk factors complicating to pulmonary embolism and the use of appropriate prophylaxis measures are the key options to the successful minimization or eradication of acute pulmonary embolism after lung resections. PMID- 26354233 TI - Hierarchical periodic micro/nano-structures on nitinol and their influence on oriented endothelialization and anti-thrombosis. AB - The applications of hierarchical micro/nano-structures, which possess properties of two-scale roughness, have been studied in various fields. In this study, hierarchical periodic micro/nano-structures were fabricated on nitinol, an equiatomic Ni-Ti alloy, using a femtosecond laser for the surface modification of intravascular stents. By controlling the laser fluence, two types of surfaces were developed: periodic nano- and micro/nano-structures. Evaluation of water contact angles indicated that the nano-surface was hydrophilic and the micro/nano surface was hydrophobic. Endothelial cells aligned along the nano-structures on both surfaces, whereas platelets failed to adhere to the micro/nano-surface. Decorrelation between the responses of the two cell types and the results of water contact angle analysis were a result of the pinning effect. This is the first study to show the applicability of hierarchical periodic micro/nano structures for surface modification of nitinol. PMID- 26354234 TI - Carbon nanotubes buckypapers for potential transdermal drug delivery. AB - Drug loaded buckypapers based on different types of carbon nanotubes (CNTs) were prepared and characterized in order to evaluate their potentialities for the design of novel transdermal drug delivery systems. Lab-synthesized CNTs as well as commercial samples were employed. Clonidine hydrochloride was used as model drug, and the influence of composition of the drug loaded buckypapers and processing variables on in vitro release profiles was investigated. To examine the influence of the drug nature the evaluation was further extended to buckypapers prepared with flurbiprofen and one type of CNTs, their selection being based on the results obtained with the former drug. Scanning electronic microscopy images indicated that the model drugs were finely dispersed on the CNTs. Differential scanning calorimetry, and X-ray diffraction pointed to an amorphous state of both drugs in the buckypapers. A higher degree of CNT-drug superficial interactions resulted in a slower release of the drug. These interactions were in turn affected by the type of CNTs employed (single wall or multiwall CNTs), their functionalization with hydroxyl or carboxyl groups, the chemical structure of the drug, and the CNT:drug mass ratio. Furthermore, the application of a second layer of drug free CNTs on the loaded buckypaper, led to decelerate the drug release and to reduce the burst effect. PMID- 26354235 TI - Synthesis of different sized and porous hydroxyapatite nanorods without organic modifiers and their 5-fluorouracil release performance. AB - Porous biocompatible hydroxyapatite (HAP) nanorods of various sizes were synthesized by the combination of chemical precipitation and hydrothermal method without the use of organic modifiers. The HAP nanorod samples were characterized by powder X-ray diffraction, transmission electron microscopy, and N2 adsorption/desorption techniques. HAP nanorods with average diameters and average lengths ranging from 8.5 to 26.6 nm and from 23.1 to 49.7 nm, respectively, could be controllably synthesized via these methods. Low autoclaving temperature and high pH value favored the formation of relatively small HAP nanorods. The TEM images showed that the nanorods possessed porous structures with average pore diameters ranging from 1.6 to 2.7 nm. These HAP nanoparticles effectively prolonged the release time of 5-fluorouracil up to 24h. The as-synthesized HAP nanorods displayed no cytotoxicity to bone marrow stem cells at low HAP concentration, indicating that these nanorod materials could serve as potential carriers for novel drug release systems. PMID- 26354236 TI - Silsesquioxane organofunctionalized with 4-amino-3-hydrazino-5-mercapto-1,2,4 triazole: Preparation and subsequent reaction with silver and potassium hexacyanoferrate(III) for detection of L-cysteine. AB - The octakis(3-chloropropyl)octasilsesquioxane (SS) was organofunctionalized with 4-amino-3-hydrazino-5-mercapto-1,2,4-triazole (Purpald). The functionalized silsesquioxane with Purpald (SP) was characterized by Fourier transform infrared spectroscopy (FT-IR), and nuclear magnetic resonance (NMR). After functionalized, silsesquioxane can interact with silver nitrate and subsequently with potassium hexacyanoferrate (III) (AgHSP). The novel hybrid composite formed (AgHSP) was characterized by Fourier transform infrared spectra, scanning electron microscopy (SEM), and energy dispersive X-ray spectroscopy (EDX). AgHSP was electrochemically characterized by cyclic voltammetry (CV) using graphite paste electrode. The AgHSP incorporated into a graphite paste electrode (20% w/w) was tested for detection of l-cysteine. The modified electrode showed a linear response from 9.0 * 10(-5) to 5.0 * 10(-3)mol L(-1) with the corresponding equation Y(A)=0.01315+1.865 [l-cysteine], and a correlation coefficient of r(2)=0.9995. The method showed a detection limit of 1.76*10(-4)mol L(-1) with a relative standard deviation of +/- 2% (n=3) and amperometric sensitivity of 1.865 A/mol L(-1). PMID- 26354237 TI - Immobilization of cholesterol oxidase on magnetic fluorescent core-shell structured nanoparticles. AB - The magnetic fluorescent core-shell structured nanoparticles, Fe3O4@SiO2(F)@meso SiO2 nanoparticles, were prepared. Cholesterol oxidase (COD) was immobilized on their surface to form Fe3O4@SiO2(F)@meso-SiO2@COD nanoparticles. Optimal immobilization was achieved with 2.5% (v/v) APTES, 2.0% (v/v) GA, 10mg COD (in 15 mg carrier) and solution pH of 7.0. Fe3O4@SiO2(F)@meso-SiO2@COD nanoparticles showed maximal catalytic activity at pH7.0 and 50 degrees C. The thermal, storage and operational stabilities of COD were improved greatly after its immobilization. After the incubation at 50 degrees C for 5h, the nanoparticles and free COD retained 80% and 46% of its initial activity, respectively. After kept at 4 degrees C for 30 days, the nanoparticles and free COD maintained 86% and 65% of initial activity, respectively. The nanoparticles retained 71% of its initial activity after 7 consecutive operations. Since Fe3O4@SiO2(F)@meso SiO2@COD nanoparticles contained tris(2,2-bipyridyl)dichloro-ruthenium(II) hexahydrate (Ru(bpy)3Cl2) and were optical sensitive to oxygen in solution, it might be used as the sensing material and has the application potential in multi parameter fiber optic biosensor based on enzyme catalysis and oxygen consumption. PMID- 26354238 TI - A highly efficient urea detection using flower-like zinc oxide nanostructures. AB - A novel matrix based on flower-like zinc oxide nanostructures (ZnONF) has been fabricated using hydrothermal method and exploited successfully for the development of urea biosensor. Urease (Urs) is physically immobilized onto the ZnO nanostructure matrix synthesized over platinized silicon substrate. The surface morphology and crystallographic structure of the as-grown ZnONF have been characterized using a scanning electron microscope (SEM) and X-ray diffraction (XRD) techniques. The fabricated amperometric biosensor (Urs/ZnONF/Pt/Ti/Si) exhibits a linear sensing response towards urea over the concentration range 1.65 mM to 16.50mM with an enhanced sensitivity (~132 MUA/mM/cm(2)) and a fast response time of 4s. The relatively low value of Michaelis-Menten constant (Km) of 0.19 mM confirms the high affinity of the immobilized urease on the nanostructured ZnONF surface towards its analyte (urea). The obtained results demonstrate that flower-like ZnO nanostructures serve as a promising matrix for the realization of efficient amperometric urea biosensor with enhanced response characteristics. PMID- 26354239 TI - Synthesis and functionalization of silica-based nanoparticles with fluorescent biocompounds extracted from Eysenhardtia polystachya for biological applications. AB - Several types of dyes or fluorophores are used for the detection of interactions between drug carriers and cells, within biomedicine field. However, many of them have a certain level of toxicity and instability affecting their biological properties. Different studies have demonstrated that nanoparticles (NPs) have interesting properties that could be used to stabilize diverse biomolecules, including dyes. Here, we report the synthesis of a novel nanosystem by the functionalization of silica NPs using biocompounds extracted from Mexican tree "Palo azul" (Eysenhardtia polystachya) and APTES as a coupling agent. Particle size, electrical properties, and morphology of the novel nanosystem were analyzed. The extracted biocompounds presented fluorescence which prevails over time, even after nanosystem formation and apparent cellular internalization. These were detected using MCF-7 cells visualized by confocal laser-scanning microscopy (CLSM), finding that the nanosystem was able to internalize into cells and act as a fluorescent biomarker. By this method, our novel nanosystem opens the possibilities to obtain sensitive data in a noninvasive manner for biological applications, such as early-stage cancer diagnosis, drug delivery, and pathogen detection. PMID- 26354240 TI - Enhancement of bioactivity on medical polymer surface using high power impulse magnetron sputtered titanium dioxide film. AB - This study utilizes a novel technique, high power impulse magnetron sputtering (HIPIMS), which provides a higher ionization rate and ion bombardment energy than direct current magnetron sputtering (DCMS), to deposit high osteoblast compatible titanium dioxide (TiO2) coatings with anatase (A-TiO2) and rutile (R-TiO2) phases onto the biomedical polyetheretherketone (PEEK) polymer substrates at low temperature. The adhesions of TiO2 coatings that were fabricated using HIPIMS and DCMS were compared. The in vitro biocompatibility of these coatings was confirmed. The results reveal that HIPIMS can be used to prepare crystallinic columnar A-TiO2 and R-TiO2 coatings on PEEK substrate if the ratio of oxygen to argon is properly controlled. According to a tape adhesion test, the HIPIMS-TiO2 coatings had an adhesion grade of 5B even after they were immersed in simulated body fluid (SBF) environments for 28days. Scratch tests proved that HIPIMS-TiO2 coatings undergo cohesive failure. These results demonstrate that the adhesive force between HIPIMS-TiO2 coating/PEEK is stronger than that between DCMS-TiO2 coating/PEEK. After a long period (28days) of immersion in SBF, a bone-like crystallinic hydroxyapatite layer with a corresponding Ca/P stoichiometry was formed on both HIPIMS-TiO2. The osteoblast compatibility of HIPIMS-TiO2 exceeded that of the bare PEEK substrate. It is also noticeable that the R-TiO2 performed better in vitro than the A-TiO2 due to the formation of many negatively charged hydroxyl groups (-OH(-)) groups on R-TiO2 (110) surface. In summary, the HIPIMS TiO2 coatings satisfied the requirements for osseointegration, suggesting the possibility of using HIPIMS to modify the PEEK surface with TiO2 for spinal implants. PMID- 26354241 TI - Bone regeneration strategy inspired by the study of calcification behavior in deer antler. AB - Bone regeneration has attracted much attention from various researchers and inspired numerous strategies for bone formation. In this study, rapid calcification of deer antlers was studied to unravel bone biology by investigating mineral composition, morphology and microstructure. Calcification model was hypothesized and preliminarily established by in vitro experiments. In our model, mineral deposition and phase conversions in the gel matrix were mimicked. Results revealed that mineral metabolism including deposition and phase conversion plays key roles in calcification in vivo, which inspired the bone regeneration strategy with three main components, i.e. enhanced mineral nucleation, mineral ions sources and crystals habits. Rapid mineral metabolism of implant apatite biomaterials was supposed as the critical aspect of bone regeneration. This study will provide a relatively ideal model for peer bone regeneration studies. PMID- 26354242 TI - An electrochemical sensor for warfarin determination based on covalent immobilization of quantum dots onto carboxylated multiwalled carbon nanotubes and chitosan composite film modified electrode. AB - A method is described for the construction of a novel electrochemical warfarin sensor based on covalent immobilization of CdS-quantum dots (CdS-QDs) onto carboxylated multiwalled carbon nanotubes/chitosan (CS) composite film on the surface of a glassy carbon electrode. The CdS-QDs/CS/MWCNTs were characterized by field-emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), Fourier transform infra-red (FTIR) spectroscopy, XRD analysis and electrochemical impedance spectroscopy (EIS). The sensor showed optimum anodic stripping response within 90s at an accumulation potential of 0.75V. The modified electrode was used to detect the concentration of warfarin with a wide linear range of 0.05-80 MUM and a detection limit (S/N=3) of 8.5 nM. The proposed sensor has good storage stability, repeatability and reproducibility and was successfully applied for the determination of warfarin in real samples such as urine, serum and milk. PMID- 26354243 TI - Bacterial adhesion on amorphous and crystalline metal oxide coatings. AB - Several studies have demonstrated the influence of surface properties (surface energy, composition and topography) of biocompatible materials on the adhesion of cells/bacteria on solid substrates; however, few have provided information about the effect of the atomic arrangement or crystallinity. Using magnetron sputtering deposition, we produced amorphous and crystalline TiO2 and ZrO2 coatings with controlled micro and nanoscale morphology. The effect of the structure on the physical-chemical surface properties was carefully analyzed. Then, we studied how these parameters affect the adhesion of Escherichia coli and Staphylococcus aureus. Our findings demonstrated that the nano-topography and the surface energy were significantly influenced by the coating structure. Bacterial adhesion at micro-rough (2.6 MUm) surfaces was independent of the surface composition and structure, contrary to the observation in sub-micron (0.5 MUm) rough surfaces, where the crystalline oxides (TiO2>ZrO2) surfaces exhibited higher numbers of attached bacteria. Particularly, crystalline TiO2, which presented a predominant acidic nature, was more attractive for the adhesion of the negatively charged bacteria. The information provided by this study, where surface modifications are introduced by means of the deposition of amorphous or crystalline oxide coatings, offers a route for the rational design of implant surfaces to control or inhibit bacterial adhesion. PMID- 26354244 TI - Nanoparticles incorporating pH-responsive surfactants as a viable approach to improve the intracellular drug delivery. AB - The pH-responsive delivery systems have brought new advances in the field of functional nanodevices and might allow more accurate and controllable delivery of specific cargoes, which is expected to result in promising applications in different clinical therapies. Here we describe a family of chitosan-TPP (tripolyphosphate) nanoparticles (NPs) for intracellular drug delivery, which were designed using two pH-sensitive amino acid-based surfactants from the family N(alpha),N(epsilon)-dioctanoyl lysine as bioactive compounds. Low and medium molecular weight chitosan (LMW-CS and MMW-CS, respectively) were used for NP preparation, and it was observed that the size distribution for NPs with LMW-CS were smaller (~168 nm) than that for NPs prepared with MMW-CS (~310 nm). Hemolysis assay demonstrated the pH-dependent biomembrane disruptional capability of the constructed NPs. The nanostructures incorporating the surfactants cause negligible membrane permeabilization at pH7.4. However, at acidic pH, prevailing in endosomes, membrane-destabilizing activity in an erythrocyte lysis assay became evident. When pH decreased to 6.6 and 5.4, hemolytic capability of chitosan NPs increased along with the raise of concentration. Furthermore, studies with cell culture showed that these pH-responsive NPs displayed low cytotoxic effects against 3T3 fibroblasts. The influence of chitosan molecular weight, chitosan to TPP weight ratio, nanoparticle size and nature of the surfactant counterion on the membrane-disruptive properties of nanoparticles was discussed in detail. Altogether, the results achieved here showed that by inserting the lysine-based amphiphiles into chitosan NPs, pH-sensitive membranolytic and potentially endosomolytic nanocarriers were developed, which, therefore, demonstrated ideal feasibility for intracellular drug delivery. PMID- 26354245 TI - Preparation, characterization and electrochemical application of Ag-ZnO nanoplates for voltammetric determination of glutathione and tryptophan using modified carbon paste electrode. AB - Ag-ZnO nanoplates and 2-chlorobenzoyl ferrocene were synthesized and used to construct a modified carbon paste electrode. The electrooxidation of glutathione at the surface of the modified electrode was studied. Under the optimized conditions, the square wave voltammetric (SWV) peak current of glutathione increased linearly with glutathione concentrations in the range of 5.0 * 10(-8) to 2.0 * 10(-4)M with sensitivity of 0.659 MUA MUM(-1) and method detection limit of 20.0 nM was obtained for glutathione. The prepared modified electrode exhibits a very good resolution between the voltammetric peaks of glutathione and tryptophan which makes it suitable for the detection of glutathione in the presence of tryptophan in real samples. PMID- 26354246 TI - Preparation and characterization of gelatin-hydroxyapatite composite microspheres for hard tissue repair. AB - Gelatin-hydroxyapatite composite microspheres composed of 21% gelatin (G) and 79% hydroxyapatite (HA) with uniform morphology and controllable size were synthesized from a mixed solution of Ca(NO3)2, NH4H2PO4 and gelatin by a wet chemical method. Material analyses such as X-ray diffraction (XRD), scanning/transmission electron microscopy examination (SEM/TEM) and inductively coupled plasma-mass spectroscopy (ICP-MS) were used to characterize G-HA microspheres by analyzing their crystalline phase, microstructure, morphology and composition. HA crystals precipitate along G fibers to form nano-rods with diameters of 6-10nm and tangle into porous microspheres after blending. The cell culture indicates that G-HA composite microspheres without any toxicity could enhance the proliferation and differentiation of osteoblast-like cells. In a rat calvarial defect model, G-HA bioactive scaffolds were compared with fibrin glue (F) and Osteoset(r) Bone Graft Substitute (OS) for their capacity of regenerating bone. Four weeks post-implantation, new bone, mineralization, and expanded blood vessel area were found in G-HA scaffolds, indicating greater osteoconductivity and bioactivity than F and OS. PMID- 26354247 TI - Study on improved tribological properties by alloying copper to CP-Ti and Ti-6Al 4V alloy. AB - Copper alloying to titanium and its alloys is believed to show an antibacterial performance. However, the tribological properties of Cu alloyed titanium alloys were seldom studied. Ti-5Cu and Ti-6Al-4V-5Cu alloys were fabricated in the present study in order to further study the friction and wear properties of titanium alloys with Cu additive. The microstructure, composition and hardness were characterized using X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscope (TEM) and hardness tester. The tribological behaviors were tested with ZrO2 counterface in 25% bovine serum using a ball-on-disc tribo-tester. The results revealed that precipitations of Ti2Cu intermetallic compounds appeared in both Ti-5Cu and Ti-6Al-4V-5Cu alloys. The tribological results showed an improvement in friction and wear resistance for both Ti-5Cu and Ti-6Al-4V-5Cu alloys due to the precipitation of Ti2Cu. The results also indicated that both CP-Ti and Ti-5Cu behaved better wear resistance than Ti-6Al-4V and Ti-6Al-4V-5Cu due to different wear mechanisms when articulated with hard zirconia. Both CP-Ti and Ti-5Cu revealed dominant adhesive wear with secondary abrasive wear mechanism while both Ti-6Al-4V and Ti-6Al-4V 5Cu showed severe abrasive wear and cracks with secondary adhesive wear mechanism due to different surface hardness integrated by their microstructures and material types. PMID- 26354248 TI - Wettability modification of human tooth surface by water and UV and electron-beam radiation. AB - The wettability of the human tooth enamel and dentin was analyzed by measuring the contact angles of a drop of distilled water deposited on the surface. The samples were cut along the transverse and longitudinal directions, and their surfaces were subjected to metallographic mirror-finish polishing. Some samples were also acid etched until their microstructure became exposed. Wettability measurements of the samples were done in dry and wet conditions and after ultraviolet (UV) and electron beam (EB) irradiations. The results indicate that water by itself was able to increase the hydrophobicity of these materials. The UV irradiation momentarily reduced the contact angle values, but they recovered after a short time. EB irradiation raised the contact angle and maintained it for a long time. Both enamel and dentin surfaces showed a wide range of contact angles, from approximately 10 degrees (hydrophilic) to 90 degrees (hydrophobic), although the contact angle showed more variability on enamel than on dentin surfaces. Whether the sample's surface had been polished or etched did not influence the contact angle value in wet conditions. PMID- 26354249 TI - Preparation, characterization, and in vitro cytotoxicity of COM and COD crystals with various sizes. AB - Calcium oxalate crystals in urine often differ in size and crystal phase between healthy humans and patients with kidney stones. In this work, calcium oxalate monohydrate (COM) and dihydrate (COD) with sizes of about 50 nm, 100 nm, 1 MUm, 3 MUm, and 10 MUm were prepared by varying reactant concentration, reaction temperature, solvent, mixing manner, and stirring speed. These crystals mainly had a smooth surface and no obvious pore structure, except COM-1 MUm. In cell culture medium, the zeta potential of crystals became increasingly negative with increasing size, and the absolute value of zeta potential of COD was greater than the same-sized COM. Results of cell viability and PI staining assays showed that the order of injury degree in African green monkey renal epithelial (Vero) cells caused by different sizes of COD was COD-50 nm>COD-100 nm>COD-1 MUm>COD-3 MUm>COD 10 MUm, and that of different sizes of COM was COM-1 MUm>COM-50~COM-100 nm>COM-3 MUm>COM-10 MUm. COM-1 MUm presented the highest cytotoxicity in Vero cells, which was associated with its rougher surface, larger specific surface area (SBET), and larger pore volume. Overall, these findings indicated that the physical properties of crystals play an important role in their cytotoxicity. PMID- 26354250 TI - In vitro cell response to Co-containing 1,393 bioactive glass. AB - Cobalt ions are known to stimulate angiogenesis via inducing hypoxic conditions and hence are interesting agents to be used in conjunction with bioactive glasses (BGs) in bone tissue engineering approaches. In this work we investigated in vitro cell biocompatibility of Co releasing 1393 BG composition (in wt.%: 53SiO2, 6Na2O, 12K2O, 5MgO, 20CaO, and 4P2O5) derived scaffolds with osteoblast-like cells (MG-63) and human dermal microvascular endothelial cells (hDMECs). Cell viability, cell number and cell morphology of osteoblast-like cells in contact with particulate glass and 3D scaffolds were assessed showing good biocompatibility of 1393 reference material and with 1 wt.% CoO addition whereby 5 wt.% of CoO in the glass showed cytotoxicity. Furthermore for 1393 with 1 wt.% of CoO increased mitochondrial activity was measured. Similar observations were made with hDMECs: while 1393 and 1393 with 1 wt.% CoO were biocompatible and the endothelial phenotype was retained, 5 wt.% CoO containing BG showed cytotoxic effects after 1 week of cell culture. In conclusion, 1 wt.% Co containing BG was biocompatible with osteoblast like cells and endothelial cells and showed slightly stimulating effects on osteoblast-like cells whereas the addition of 5 wt.% CoO seems to exceed the vital therapeutic ranges of Co ions being released in physiological fluids. PMID- 26354251 TI - A novel composite electrode based on tungsten oxide nanoparticles and carbon nanotubes for the electrochemical determination of paracetamol. AB - An electrochemical sensor was prepared by the modification of a glassy carbon electrode (GCE) with a composite of nanoparticles of tungsten oxide (WO3) and carbon nanotubes (CNTs) for the quantification of paracetamol (PR). Energy dispersive X-ray analysis (EDX) and scanning electron microscopy (SEM) were performed for the characterization of the nanocomposite layer. Compared with a bare GCE and a GCE modified with CNTs, the proposed electrode (WO3NPs/CNTs/GCE) exhibited a well-defined redox couple for PR and a marked enhancement of the current response. The experimental results also showed that ascorbic acid (AA) did not interfere with the selective determination of PR. The proposed electrode was used for the determination of PR in 0.1M phosphate buffer solution (PBS) at pH7.0 using square wave voltammetry (SWV). The peak current increased linearly with the concentration of PR in the range of 1.0*10(-9)-2.0*10(-7)M. The detection limit (LOD) was 5.54*10(-11)M (based on 3Sb/m). The proposed voltammetric sensor provided long-time stability, improved voltammetric behavior and good reproducibility for PR. The selective, accurate and precise determination of PR makes the proposed electrode of great interest for monitoring its therapeutic use. PMID- 26354252 TI - Adsorption mechanisms of L-Glutathione on Au and controlled nano-patterning through Dip Pen Nanolithography. AB - Dip Pen Nanolithography technique has been employed for patterning L-Glutathione tripeptide (l-y-glutamyl-l-cysteinyl-glycine) nanostructures at specific locations on metallic Au(111) substrate. The formed supramolecular architectures were designed through straight lines and dots serving as precursors for building blocks assemblies in nano-bio-electronics applications or as template structures for functionalized particles in the form of host-guest networks. Tween 20 polyoxyethylene surfactant concentrations ranging from 0.005 to 0.1% (v/v) into initial l-Glutathione tripeptide (2 mg mL(-1)) ink solutions were sequentially tested for the improvement of the ink delivery process and to assure an optimum uniformity and homogeneity over the patterned space. A strong relationship was found between the coated atomic force microscope (AFM) cantilever within the highly effective Tween 20 activator adjuvant and the molecular diffusion along concentration gradients. An increase in the driving force for ink transport from the AFM tip has been demonstrated within the highest 0.1% (v/v) TW 20 surfactant concentration, favoring the patterning of GSH molecules routinely with sub-100 nm resolution. Self-assembled monolayers of GSH were also fabricated and characterized in the light of X-ray photoemission spectroscopy (XPS) and ellipsometric optical measurements. Adsorption from water of l-Glutathione to the gold substrate is proven to be made by the thiol group of cysteine. Theoretical DFT approaches were applied for quantum chemical studies dedicated to electronic processes underneath molecular GSH/Au(111) systems. PMID- 26354253 TI - Three-dimensional graphene foams loaded with bone marrow derived mesenchymal stem cells promote skin wound healing with reduced scarring. AB - The regeneration of functional skin remains elusive, due to poor engraftment, deficient vascularization, and excessive scar formation. Aiming to overcome these issues, the present study proposed the combination of a three-dimensional graphene foam (GF) scaffold loaded with bone marrow derived mesenchymal stem cells (MSCs) to improve skin wound healing. The GFs demonstrated good biocompatibility and promoted the growth and proliferation of MSCs. Meanwhile, the GFs loaded with MSCs obviously facilitated wound closure in animal model. The dermis formed in the presence of the GF structure loaded with MSCs was thicker and possessed a more complex structure at day 14 post-surgery. The transplanted MSCs correlated with upregulation of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), which may lead to neo-vascularization. Additionally, an anti-scarring effect was observed in the presence of the 3D-GF scaffold and MSCs, as evidenced by a downregulation of transforming growth factor beta 1 (TGF-beta1) and alpha-smooth muscle actin (alpha-SMA) together with an increase of TGF-beta3. Altogether, the GF scaffold could guide the wound healing process with reduced scarring, and the MSCs were crucial to enhance vascularization and provided a better quality neo-skin. The GF scaffold loaded with MSCs possesses necessary bioactive cues to improve wound healing with reduced scarring, which may be of great clinical significance for skin wound healing. PMID- 26354254 TI - Novel hydrogels based on carboxyl pullulan and collagen crosslinking with 1, 4 butanediol diglycidylether for use as a dermal filler: initial in vitro and in vivo investigations. AB - Novel hydrogels based on carboxyl pullulan (PC) and human-like collagen (HLC) crosslinking with 1,4-butanediol diglycidyl ether (BDDE) are promising soft fillers for tissue engineering due to their highly tunable properties. Recent studies, however, have shown that incorporating hyaluronic acid and BDDE results in hydrogels with a microporous structure, a large pore size and high porosity, which reduce cell adhesion and enhance degradation in vivo. To improve biocompatibility and prevent biodegradation, the use of PC to replace hyaluronic acid in the fabrication of PC/BDDE (PCB) and PC/BDDE/HLC (PCBH) hydrogels was investigated. Preparation of gels with PC is a promising strategy due to the high reactivity, superb selectivity, and mild reaction conditions of PC. In particular, the Schiff base reaction of HLC and PC produces the novel functional group -RCONHR' in PCBH hydrogels. Twenty-four weeks after subcutaneous injection of either PCB or PCBH hydrogel in mice, the surrounding tissue inflammation, enzymatic response and cell attachment were better compared to hyaluronic acid based hydrogels. However, the biocompatibility, cytocompatibility and non biodegradability of PCBH were milder than those of the PCB hydrogels both in vivo and in vitro. These results show that the proposed use of PC and HLC for the fabrication of hydrogels is a promising strategy for generating soft filler for tissue engineering. PMID- 26354255 TI - Electrochemical sensor for Isoniazid based on the glassy carbon electrode modified with reduced graphene oxide-Au nanomaterials. AB - A sensitive electrochemical sensor has been fabricated to detect Isoniazid (INZ) using reduced graphene oxide (RGO) and Au nanocomposites (RGO-Au). RGO-Au nanocomposites were synthesized by a solution-based approach of chemical co reduction of Au(III) and graphene oxide (GO), and were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), Raman spectroscopy, and Fourier transform infrared (FT-IR). The Au nanoparticles separate the RGO sheets in the precipitate and prevent RGO sheets from aggregation upon pi-pi stacking interactions. RGO-Au nanocomposites were used to modify the glassy carbon electrode (GCE). The electrochemical properties of RGO-Au/GCE were investigated by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS), and the RGO-Au/GCE exhibited remarkably strong electrocatalytic activities towards INZ. Under the optimized conditions, there was linear relationships between the peak currents and the concentrations in the range of 1.0*10(-7)M to 1.0*10(-3)M for INZ, with the limit of detection (LOD) (based on S/N=3) of 1.0*10(-8)M for INZ. PMID- 26354256 TI - A novel electrochemical sensor based on magneto Au nanoparticles/carbon paste electrode for voltammetric determination of acetaminophen in real samples. AB - An electrochemical magneto Au nanoparticles/carbon paste electrodes (MAuNP/CPE) which is used for the determination of acetaminophen (AC) in real samples was developed. Initially, Au nanoparticles were immobilized at the surface of Fe3O4 (AuNPs@Fe3O4), which was used as a sorbent for capturing AC molecules. After adding AuNPs@Fe3O4 to the AC solution and stirring for 20 min, the AuNPs@Fe3O4 was gathered on the magneto electrode based on its magnetic field. The AC molecules which became adsorbed at AuNPs@Fe3O4 were analyzed by differential pulse voltammetry (DPV). For characterization and investigation of the performance of AuNPs@Fe3O4 and MAuNPs/CPE, various methods, including scanning electron microscopy, X-ray diffraction, UV-Vis spectroscopy, electrochemical impedance spectroscopy, cyclic voltammetry and DPV were used. Under the optimized conditions, the anodic peak current was linear to the concentration of AC in the range of 0.1 to 70.0MUmol L(-1) with the detection limit of 4.5*10(-2)MUmol L( 1). This method was also successfully used to detect the concentration of AC in pharmaceutical formulations and human serum samples. In addition, the proposed magneto sensor exhibited good reproducibility, long-term stability and fast current response. PMID- 26354257 TI - Comfort and compressional characteristics of padding bandages. AB - BACKGROUND: Padding bandage is an essential component of the multi-layer compression system used for chronic venous management. Padding plays a critical role in managing pressure over bony prominences and ensuring uniform pressure distribution around the limb circumference. Moreover, it helps in the management of heat, moisture and body fluids or exudates during the course of treatment to provide comfort to the patients. OBJECTIVE: To study the effect of structural and constructional parameters on the compressional (pressure absorption or distribution) and comfort (air, moisture and heat transmission) characteristics of the padding. METHODS: This research focuses on the examination of polypropylene based nonwoven padding samples. Critical factors, i.e., fiber linear density, needling density and mass per unit area, have been chosen for this study to find their significance on the performance of padding. Simple laboratory based methods have been proposed to examine pressure reduction and comfort characteristics of the padding. RESULTS: Pressure absorption by the padding decreases with increase in mass per unit area and needling density of the padding. A padding composed of thicker fiber absorbs more pressure compared to padding made from thinner fiber. On examining comfort, it was found that the air and moisture vapor transmission increase with decrease in mass per unit area and needling density but have opposite effects with fiber linear density (p<0.01). The heat transmission decreases with increase in both mass per unit area and fiber linear density but has opposite effect for needling density. CONCLUSION: Padding composed of thick fiber with low mass per unit area and needling density could be more effective in pressure management and ensuring comfort. These results could be very useful for health practitioners, fabric engineers and manufactures to understand the significance of fibrous materials and their role in compression management, and could be further used as design consideration to optimized padding performance. PMID- 26354258 TI - Cytotoxicity assessment of functionalized CdSe, CdTe and InP quantum dots in two human cancer cell models. AB - The toxicity of quantum dots (QDs) has been extensively studied over the past decade. Some common factors that originate the QD toxicity include releasing of heavy metal ions from degraded QDs and the generation of reactive oxygen species on the QD surface. In addition to these factors, we should also carefully examine other potential QD toxicity causes that will play crucial roles in impacting the overall biological system. In this contribution, we have performed cytotoxicity assessment of four types of QD formulations in two different human cancer cell models. The four types of QD formulations, namely, mercaptopropionic acid modified CdSe/CdS/ZnS QDs (CdSe-MPA), PEGylated phospholipid encapsulated CdSe/CdS/ZnS QDs (CdSe-Phos), PEGylated phospholipid encapsulated InP/ZnS QDs (InP-Phos) and Pluronic F127 encapsulated CdTe/ZnS QDs (CdTe-F127), are representatives for the commonly used QD formulations in biomedical applications. Both the core materials and the surface modifications have been taken into consideration as the key factors for the cytotoxicity assessment. Through side-by side comparison and careful evaluations, we have found that the toxicity of QDs does not solely depend on a single factor in initiating the toxicity in biological system but rather it depends on a combination of elements from the particle formulations. More importantly, our toxicity assessment shows different cytotoxicity trend for all the prepared formulations tested on gastric adenocarcinoma (BGC-823) and neuroblastoma (SH-SY5Y) cell lines. We have further proposed that the cellular uptake of these nanocrystals plays an important role in determining the final faith of the toxicity impact of the formulation. The result here suggests that the toxicity of QDs is rather complex and it cannot be generalized under a few assumptions reported previously. We suggest that one have to evaluate the QD toxicity on a case to case basis and this indicates that standard procedures and comprehensive protocols are urgently needed to be developed and employed for fully assessing and understanding the origins of the toxicity arising from different QD formulations. PMID- 26354259 TI - Polycaprolactone thin-film drug delivery systems: Empirical and predictive models for device design. AB - PURPOSE: To define empirical models and parameters based on theoretical equations to describe drug release profiles from two polycaprolactone thin-film drug delivery systems. Additionally, to develop a predictive model for empirical parameters based on drugs' physicochemical properties. METHODS: Release profiles from a selection of drugs representing the standard pharmaceutical space in both polycaprolactone matrix and reservoir systems were determined experimentally. The proposed models were used to calculate empirical parameters describing drug diffusion and release. Observed correlations between empirical parameters and drug properties were used to develop equations to predict parameters based on drug properties. Predictive and empirical models were evaluated in the design of three prototype devices: a levonorgestrel matrix system for on-demand locally administered contraception, a timolol-maleate reservoir system for glaucoma treatment, and a primaquine-bisphosphate reservoir system for malaria prophylaxis. RESULTS: Proposed empirical equations accurately fit experimental data. Experimentally derived empirical parameters show significant correlations with LogP, molecular weight, and solubility. Empirical models based on predicted parameters accurately predict experimental release data for three prototype systems, demonstrating the accuracy and utility of these models. CONCLUSION: The proposed empirical models can be used to design polycaprolactone thin-film devices for target geometries and release rates. Empirical parameters can be predicted based on drug properties. Together, these models provide tools for preliminary evaluation and design of controlled-release delivery systems. PMID- 26354260 TI - Bioactivity studies on TiO2-bearing Na2O-CaO-SiO2-B2O3 glasses. AB - Soda lime silica borate glasses mixed with different concentrations of TiO2 are synthesized by the melt-quenching technique. As a part of study on bioactivity of these glasses, the samples were immersed in simulated body fluid (SBF) solution for prolonged times (~21 days) during which weight loss along with pH measurements is carried out at specific intervals of time. The XRD and SEM analyses of post-immersed samples confirm the formation of crystalline hydroxyapatite layer (HA) on the surface of the samples. To assess the role of TiO2 on the formation of HA layer and degradability of the samples the spectroscopic studies viz. optical absorption and IR spectral studies on post- and pre-immersed samples have been carried out. The analysis of the results of degradability together with spectroscopic studies as a function of TiO2 concentration indicated that about 6.0 mol% of TiO2 is the optimal concentration for achieving better bioactivity of these glasses. The presence of the maximal concentration octahedral titanium ions in this glass that facilitates the formation of HA layer is found to be the reason for such a higher bioactivity. PMID- 26354261 TI - Does L to D-amino acid substitution trigger helix->sheet conformations in collagen like peptides adsorbed to surfaces? AB - The present work reports on the structural order, self assembling behaviour and the role in adsorption to hydrophilic or hydrophobic solid surfaces of modified sequence from the triple helical peptide model of the collagenase cleavage site in type I collagen (Uniprot accession number P02452 residues from 935 to 970) using (D)Ala and (D)Ile substitutions as given in the models below: Model-1: GSOGADGPAGAOGTOGPQGIAGQRGVV GLOGQRGER. Model-2: GSOGADGP(D)AGAOGTOGPQGIAGQRGVVGLOGQRGER. Model-3: GSOGADGPAGAOGTOGPQG(D)IAGQRGVVGLOGQRGER. Collagenase is an important enzyme that plays an important role in degrading collagen in wound healing, cancer metastasis and even in embryonic development. However, the mechanism by which this degradation occurs is not completely understood. Our results show that adsorption of the peptides to the solid surfaces, specifically hydrophobic triggers a helix to beta transition with order increasing in peptide models 2 and 3. This restricts the collagenolytic behaviour of collagenase and may find application in design of peptides and peptidomimetics for enzyme-substrate interaction, specifically with reference to collagen and other extra cellular matrix proteins. PMID- 26354262 TI - Synthesis of dendritic silver nanostructures supported by graphene nanosheets and its application for highly sensitive detection of diazepam. AB - In this paper, preparation, characterization and application of a new sensor for fast and simple determination of trace amount of diazepam were described. This sensor is based on Ag nanodendrimers (AgNDs) supported by graphene nanosheets modified glassy carbon electrode (GNs/GCE). The AgNDs were directly electrodeposited on the surface of electrode via potentiostatic method without using any templates, surfactants, or stabilizers. The structure of the synthesized AgNDs/GNs was characterized by scanning electron microscopy (SEM), energy dispersive X-ray (EDX) analysis, X-ray diffraction (XRD) and electrochemical impedance spectroscopy (EIS) techniques. The nanodendrimers with tree-like and hierarchical structures have a fascinating structure for fabrication of effective electrocatalysts. The experimental results confirmed that AgNDs/GNs/GC electrode has good electrocatalytic activity toward the reduction of diazepam. A low detection limit of 8.56*10(-8)M and a wide linear detection range of 1.0*10(-7) to 1.0*10(-6)M and 1.0*10(-6) to 20*10(-6)M were achieved via differential pulse voltammetry (DPV). The proposed electrode displayed excellent repeatability and long-term stability and it was satisfactorily used for determination of diazepam in real samples (commercially tablet, injection and human blood plasma) with high recovery. PMID- 26354263 TI - Design of a novel coumarin-based multifunctional fluorescent probe for Zn2+/Cu2+/S2- in aqueous solution. AB - A multifunctional fluorescent chemosensor 7-(diethylamino)-coumarin-3 carbaldehyde-(2'-methylquinoline-4'-formyl) hydrazone (HL) has been designed and synthesized. The sensor shows significant fluorescence enhancement in the presence of Zn(2+), which might be mainly due to the restricted -CN isomerization process. In contrast, the fluorescence of the sensor is quenched by Cu(2+) attributed to the inherent paramagnetic species. More interestingly, the 'in situ' prepared L-Cu exhibits a selective response to S(2-) based on reversible formation-separation of complex L-Cu and CuS. PMID- 26354264 TI - Methotrexate intercalated layered double hydroxides with the mediation of surfactants: Mechanism exploration and bioassay study. AB - Methotrexatum intercalated layered double hydroxides (MTX/LDHs) hybrids were synthesized by the co-precipitation method and three kinds of nonionic surfactants with different hydrocarbon chain lengths were used. The resulting hybrids were then characterized by X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy and transmission electron microscopy (TEM). XRD and FTIR investigations manifest the successful intercalation of MTX anions into the interlayer of LDHs. TEM graphs indicate that the morphology of the hybrids changes with the variation of the chain length of the surfactants, i.e., the particles synthesized using polyethylene glycol (PEG-7) present regular disc morphology with good monodispersity, while samples with the mediation of alkyl polyglycoside (APG-14) are heavily aggregated and samples with the addition of polyvinylpyrrolidone (PVP-10) exhibit irregular branches. Furthermore, the release and bioassay experiments show that monodisperse MTX/LDHs present good controlled-release and are more efficient in the suppression of the tumor cells. PMID- 26354265 TI - An electrochemical sensor for gallic acid based on Fe2O3/electro-reduced graphene oxide composite: Estimation for the antioxidant capacity index of wines. AB - A highly sensitive electrochemical sensor for gallic acid (GA), an important polyphenolic compound, was fabricated using the hybrid material of chitosan (CS), fishbone-shaped Fe2O3 (fFe2O3), and electrochemically reduced graphene oxide (ERGO) as the sensing matrix. The electrochemical characterization experiments showed that the CS-fFe2O3-ERGO modified glassy carbon electrode (CS-fFe2O3 ERGO/GCE) had large surface area, excellent electronic conductivity and high stability. The GA presented a superior electrochemical response on CS-fFe2O3 ERGO/GCE in comparison with the single-component modified electrode. The electrochemical mechanism and optimal test conditions of GA on the electrode surface were carefully investigated. Under the optimal conditions, the oxidation peak currents in differential pulse voltammetry (DPV) experiments exhibited a good linear relationship with the logarithmic values of GA concentration over the range from 1.0*10(-6)M to 1.0*10(-4)M. Based on signal-to-noise (S/N) characteristic of 3, the detection limit was estimated to be 1.5*10(-7)M. The proposed sensor has also been applied for estimating the antioxidant capacity index of real samples of red and white wines. PMID- 26354266 TI - On the mechanical properties of PLC-bioactive glass scaffolds fabricated via BioExtrusion. AB - This paper addresses the mechanical characterization of polycaprolactone (PCL) bioglass (FastOs(r)BG) composites and scaffolds intended for use in tissue engineering. Tissue engineering scaffolds support the self-healing mechanism of the human body and promote the regrowth of damaged tissue. These implants can dissolve after successful tissue regeneration minimising the immune reaction and the need for revision surgery. However, their mechanical properties should match surrounding tissue in order to avoid strain concentration and possible separation at the interface. Therefore, an extensive experimental testing programme of this advanced material using uni-axial compressive testing was conducted. Tests were performed at low strain rates corresponding to quasi-static loading conditions. The initial elastic gradient, plateau stress and densification strain were obtained. Tested specimens varied according to their average density and material composition. In total, four groups of solid and robocast porous PCL samples containing 0, 20, 30, and 35% bioglass, respectively were tested. The addition of bioglass was found to slightly decrease the initial elastic gradient and the plateau stress of the biomaterial scaffolds. PMID- 26354267 TI - Effects of grain refinement on the biocorrosion and in vitro bioactivity of magnesium. AB - Magnesium is a new class of biodegradable metals potentially suitable for bone fracture fixation due to its suitable mechanical properties, high degradability and biocompatibility. However, rapid corrosion and loss in mechanical strength under physiological conditions render it unsuitable for load-bearing applications. In the present study, grain refinement was implemented to control bio-corrosion demonstrating improved in vitro bioactivity of magnesium. Pure commercial magnesium was grain refined using different amounts of zirconium (0.25 and 1.0 wt.%). Corrosion behavior was studied by potentiodynamic polarization (PDP) and mass loss immersion tests demonstrating corrosion rate decrease with grain size reduction. In vitro biocompatibility tests conducted by MC3T3-E1 pre osteoblast cells and measured by DNA quantification demonstrate significant increase in cell proliferation for Mg-1 wt.% Zr at day 5. Similarly, alkaline phosphatase (ALP) activity was higher for grain refined Mg. Alloys were also tested for ability to support osteoclast differentiation using RAW264.7 monocytes with receptor activator of nuclear factor kappa-beta ligand (RANKL) supplemented cell culture. Osteoclast differentiation process was observed to be severely restricted for smaller grained Mg. Overall, the results indicate grain refinement to be useful not only for improving corrosion resistance of Mg implants for bone fixation devices but also potentially modulate bone regeneration around the implant. PMID- 26354268 TI - Design of an optically stable pH sensor based on immobilization of Giemsa on triacetylcellulose membrane. AB - In this work a simple, inexpensive, and sensitive optical sensor based on triacetylcellulose membrane as solid support was developed by using immobilization of Giemsa indicator for pH measurement. In this method, the influence variables on the membrane performance including pH concentration of indicator, response time, ionic strength, and reversibility were investigated. At optimum values of all variables the response of optical pH sensor is linear in the pH range of 3.0-12.0. This optical sensor was produced through simultaneous binding of the Giemsa on the activated triacetylcellulose membrane which responded to the pH changes in a broader linear range within less than 2.0 min and suitable reproducibility (RSD<5%). Stability results showed that this sensor was stable after 6 months of storage in the water/ethanol (50:50, v/v) solution without any measurable divergence in response properties (less than 5% RSD). PMID- 26354269 TI - Microstructure and corrosion behavior of laser processed NiTi alloy. AB - Laser Engineered Net Shaping (LENSTM), a commercially available additive manufacturing technology, has been used to fabricate dense equiatomic NiTi alloy components. The primary aim of this work is to study the effect of laser power and scan speed on microstructure, phase constituents, hardness and corrosion behavior of laser processed NiTi alloy. The results showed retention of large amount of high-temperature austenite phase at room temperature due to high cooling rates associated with laser processing. The high amount of austenite in these samples increased the hardness. The grain size and corrosion resistance were found to increase with laser power. The surface energy of NiTi alloy, calculated using contact angles, decreased from 61 mN/m to 56 mN/m with increase in laser energy density from 20 J/mm(2) to 80 J/mm(2). The decrease in surface energy shifted the corrosion potentials to nobler direction and decreased the corrosion current. Under present experimental conditions the laser power found to have strong influence on microstructure, phase constituents and corrosion resistance of NiTi alloy. PMID- 26354270 TI - Poly(lactic acid)/TiO2 nanocomposites as alternative biocidal and antifungal materials. AB - Poly(lactic acid) (PLA) composites with titanium oxide (TiO2) ~10-nm nanoparticles were produced by the melting process and their main properties were evaluated. The nanoparticles are homogeneously dispersed in the matrix with a low degree of agglomeration, as seen by transmission electron microscopy (TEM). The crystallinity temperature increased ~12% when 5 wt.% of TiO2 was added, showing that the nanoparticles acted as nucleating agents this trend was confirmed by optical images. The elastic modulus increased ~54% compared to neat PLA at 5 wt.% of nanoparticles. Despite these improvements, PLA/TiO2 nanocomposites showed lower shear viscosity than neat PLA, possibly reflecting degradation of the polymer due to the particles. Regarding biocidal properties, after 2h of contact the PLA/TiO2 composites with 8 wt.% TiO2 showed a reduction of Escherichia coli colonies of ~82% under no UVA irradiation compared to pure PLA. This biocidal characteristic can be increased under UVA irradiation, with nanocomposites containing 8 wt.% TiO2 killing 94% of the bacteria. The PLA/TiO2 nanocomposites with 8 wt.% were also 99.99% effective against Aspergillus fumigatus under the UVA irradiation. PMID- 26354271 TI - IR 820 dye encapsulated in polycaprolactone glycol chitosan: Poloxamer blend nanoparticles for photo immunotherapy for breast cancer. AB - In the present study, we have fabricated biocompatible and biodegradable monodisperse IR 820 encapsulated polycaprolactone (PCL) glycol chitosan (GC): Poloxamer blend nanoparticles (PP-IR NPs) for imaging and effective photo immunotherapy. IR 820 has been used as an imaging and photothermal agent whereas glycol chitosan (GC) as an immunostimulatory agent. The combination of IR 820, poloxamer, and GC can be used effectively for photoimmunotherapy for cancer, drug resistant and TNF-alpha resistant estrogen positive breast cancer. PP-IR NPs are stable in aqueous solution. The uniform size of 100-220 nm with a high zeta value of +38 +/- 2 mV led them to accumulate in cancer cells. Laser treatment did not affect the morphology of PP-IR NPs as observed under the transmission electron microscope (TEM). In vitro cytotoxicity studies on MCF-7 cells showed enhanced toxicity upon laser treatment. Further, we validated the cell death by reactive oxygen species (ROS) production. Our studies thus showed that PP-IR NPs are effective in suppressing metastatic cancer as the combinational therapy leads to the formation of apoptotic bodies in MCF-7 cells. PMID- 26354273 TI - The effect of post-mastectomy radiation therapy on breast implants: Unveiling biomaterial alterations with potential implications on capsular contracture. AB - Post-mastectomy breast reconstruction with expanders and implants is recognized as an integral part of breast cancer treatment. Its main complication is represented by capsular contracture, which leads to poor expansion, breast deformation, and pain, often requiring additional surgery. In such a scenario, the debate continues as to whether the second stage of breast reconstruction should be performed before or after post-mastectomy radiation therapy, in light of potential alterations induced by irradiation to silicone biomaterial. This work provides a novel, multi-technique approach to unveil the role of radiotherapy in biomaterial alterations, with potential involvement in capsular contracture. Following irradiation, implant shells underwent mechanical, chemical, and microstructural evaluation by means of tensile testing, Attenuated Total Reflectance Fourier Transform InfraRed spectroscopy (ATR/FTIR), Scanning Electron Microscopy (SEM), high resolution stylus profilometry, and Time of Flight Secondary Ion Mass Spectrometry (ToF-SIMS). Our findings are consistent with radiation-induced modifications of silicone that, although not detectable at the microscale, can be evidenced by more sophisticated nanoscale surface analyses. In light of these results, biomaterial irradiation cannot be ruled out as one of the possible co-factors underlying capsular contracture. PMID- 26354272 TI - Iron nanoparticles decorated multi-wall carbon nanotubes modified carbon paste electrode as an electrochemical sensor for the simultaneous determination of uric acid in the presence of ascorbic acid, dopamine and L-tyrosine. AB - Iron nanoparticles decorated multi-wall carbon nanotubes modified carbon paste electrode (Fe-MWCNTs/MCPE) was prepared by bulk-modification method. The electrochemical impedance spectroscopy (EIS) suggests least charge transfer resistance at the modified electrode. The electrochemical behavior of UA was studied in 0.1M phosphate buffer solution (PBS) of pH3.0 using cyclic voltammetry (CV) while differential pulse voltammetry (DPV) was used for quantification. The spectroelectrochemial study of oxidation of UA at Fe-MWCNTs/MCPE showed a decrease in the absorbance of two peaks with time, which are ascribed to pi to pi(*) and n to pi(*) transitions. Under optimum condition, the DPV response offered two linear dynamic ranges for UA in the concentration range 7.0*10(-8)M 1.0*10(-6)M and 2.0*10(-6)M-1.0*10(-5)M with detection limit (4.80+/-0.35)*10( 8)M (S/N=3). The practical analytical application of this sensor was successfully evaluated by determination of spiked UA in clinical samples, such as human blood serum and urine with good percentage recovery. The proposed electrochemical sensor offers a simple, reliable, rapid, reproducible and cost effective analysis of a quaternary mixture of biomolecules containing AA, DA, UA and Tyr which was free from mutual interferences. PMID- 26354274 TI - Electrochemical investigation of the voltammetric determination of hydrochlorothiazide using a nickel hydroxide modified nickel electrode. AB - The preparation and electrochemical characterization of a nickel hydroxide modified nickel electrode as well as its behavior as electrocatalyst toward the oxidation of hydrochlorothiazide (HCTZ) were investigated. The electrochemical behavior of the modified electrode and the electrooxidation of HCTZ were explored using cyclic voltammetry. The voltammetric response of the modified electrode in the detection of HCTZ is based on the electrochemical oxidation of the Ni(II)/Ni(III) and a chemical redox process. The analytical parameters for the electrooxidation of HCTZ by the nickel hydroxide modified nickel electrode were obtained in NaOH solution, in which the linear voltammetric response was in the concentration range from 1.39*10(-5) to 1.67*10(-4)mol L(-1) with a limit of detection of 7.92*10(-6)mol L(-1) and a sensitivity of 0.138 MUA Lmmol(-1). Tafel analysis was used to elucidate the kinetics and mechanism of HCTZ oxidation by the modified electrode. PMID- 26354275 TI - Mechanical degradation of porous titanium with entangled structure filled with biodegradable magnesium in Hanks' solution. AB - The degradation behavior of the porous titanium with entangled structure filled with biodegradable magnesium (p-Ti/Mg) in Hanks' solution was investigated. It was found that the p-Ti/Mg composite had higher strength than pure magnesium and porous titanium with entangled structure (p-Ti). Although the magnesium in p Ti/Mg was completely dissolved in Hanks' solution after immersion for 104 h, the rest of the sample still maintained strength of about 86 MPa. Moreover, the produced porousness (due to magnesium-degradation) could provide channels for the ingrowth and transportation of bone cells. However, the high corrosion rate of p Ti/Mg is still a problem when used as a candidate biomedical material, which needs further improvement. PMID- 26354276 TI - Influence of saline solution on hydration behavior of beta-dicalcium silicate in comparison with biphasic calcium phosphate/hydroxyapatite bio-ceramics. AB - The influence of using saline solution as mixing and curing liquid on some characteristics of beta-dicalcium silicate (beta-C2S) and biphasic compound tri calcium phosphate/hydroxyapatite (TCP/HAp) bio-ceramics was investigated. beta C2S (27-30 nm) was prepared by solid state reaction at 1450 degrees C, while biphasic compound TCP/HAp (7-15 nm) was synthesized from an aqueous solution of Ca(NO3)2.4H2O and (NH4)2HPO4.12H2O by chemical precipitation method. Setting times, compressive strength, pH values, X-ray diffraction analysis, infrared spectroscopy, scanning electron microscopy (SEM) were investigated. The evaluation of cytotoxicity of both calcium silicate and biphasic compounds to human gingival fibroblasts was carried out. The use of saline solution as mixing and immersing liquid shortened the setting time for the two bio-cements. TCP/HAp did not show any mechanical strength but beta-C2S showed good strength values. Both synthesized compounds showed a moderate cytotoxicity and both materials were effective in a no significant way. PMID- 26354277 TI - Osteoblast response to zirconia surfaces with different topographies. AB - Zirconia-3 mol% yttria ceramics were prepared with as-sintered, abraded, polished, and porous surfaces in order to explore the attachment, proliferation and differentiation of osteoblast-like cells. After modification, all surfaces were heated to 600 degrees C to extinguish traces of organic contamination. All surfaces supported cell attachment, proliferation and differentiation but the surfaces with grain boundary grooves or abraded grooves provided conditions for enhanced initial cell attachment. Nevertheless, overall cell proliferation and total DNA were highest on the polished surface. Zirconia sintered at a lower temperature (1300 degrees C vs. 1450 degrees C) had open porosity and presented reduced proliferation as assessed by alamarBlueTM assay, possibly because the openness of the pores prevented cells developing a local microenvironment. All cells retained the typical polygonal morphology of osteoblast-like cells with variations attributable to the underlying surface notably alignment along the grooves of the abraded surface. PMID- 26354278 TI - Ratcheting behavior of articular cartilage under cyclic unconfined compression. AB - The ratcheting deformation of articular cartilage can produce due to the repeated accumulations of compressive strain in cartilage. The aim of this study was to investigate the ratcheting behavior of articular cartilage under cyclic compression. A series of uniaxial cyclic compression tests were conducted for online soaked and unsoaked cartilage samples and the effects of stress variation and stress rate on ratcheting behavior of cartilage were investigated. It is found that the ratcheting strains of online soaked and unsoaked cartilage samples increase rapidly at initial stage and then show the slower increase with cyclic compression going on. On the contrary, the ratcheting strain rate decreases quickly at first and then exhibits a relatively stable and small value. Both the ratcheting strain and ratcheting strain rate increase with stress variation increasing or with stress rate decreasing. Simultaneously, the optimized digital image correlation (DIC) technique was applied to study the ratcheting behavior and Young's modulus of different layers for cartilage under cyclic compression. It is found that the ratcheting behavior of cartilage is dependent on its depth. The ratcheting strain and its rate decrease through the depth of cartilage from surface to deep, whereas the Young's modulus increases. PMID- 26354279 TI - Determination of dopamine in presence of ascorbic acid and uric acid using poly (Spands Reagent) modified carbon paste electrode. AB - In this paper, we have fabricated a modified carbon paste electrode (CPE) by electropolymerisation of spands reagent (SR) onto surface of CPE using cyclic voltammetry (CV). The developed electrode was abbreviated as poly(SR)/CPE and the surface morphology of the modified electrode was studied by using scanning electron microscopy (SEM). The developed electrode showed higher electrocatalytic properties towards the detection of dopamine (DA) in 0.1M phosphate buffer solution (PBS) at pH7.0. The effect of pH, scan rate, accumulation time and concentration of dopamine was studied at poly(SR)/CPE. The poly(SR)/CPE was successfully used as a sensor for the selective determination of DA in presence of ascorbic acid (AA) and uric acid (UA) without any interference. The poly(SR)/CPE showed a good detection limit of 0.7 MUM over the linear dynamic range of 1.6 MUM to 16 MUM, which is extremely lower than the reported methods. The prepared poly(SR)/CPE exhibited good stability, high sensitivity, better reproducibility, low detection limit towards the determination of DA. The developed method was also applied for the determination of DA in real samples. PMID- 26354280 TI - Disposable urea biosensor based on nanoporous ZnO film fabricated from omissible polymeric substrate. AB - In the present study, a facile and simple fabrication method of a semiconductor based urea biosensor was reported via three steps: (i) producing a ZnO-PVA composite film by means of a polymer assisted electrodeposition of zinc oxide (ZnO) on the F-doped SnO2 conducting glass (FTO) using water soluble polyvinyl alcohol (PVA), (ii) obtaining a nanoporous ZnO film by PVA omission via a subsequent post-treatment by annealing of the ZnO-PVA film, and (iii) preparation of a FTO/ZnO/Urs biosensor by exploiting a nanoporous ZnO film as an efficient and excellent platform area for electrostatic immobilization of urease enzyme (Urs) which was forced by the difference in their isoelectric point (IEP). The characterization techniques focused on the analysis of the ZnO-PVA film surfaces before and after annealing, which had a prominent effect on the porosity of the prepared ZnO film. The surface characterization of the nanostructured ZnO film by a field emission-scanning electron microscopy (FE-SEM), exhibited a film surface area as an effective bio-sensing matrix for enzyme immobilization. The structural characterization and monitoring of the biosensor fabrication was performed using UV-Vis, Fourier Transform Infrared (FT-IR), Raman Spectroscopy, Thermogravimetric Analysis (TGA), Cyclic Voltammetry (CV), and Electrochemical Impedance Spectroscopy (EIS) techniques. The impedimetric results of the FTO/ZnO/Urs biosensor showed a high sensitivity for urea detection within 8.0-110.0mg dL(-1) with the limit of detection as 5.0mg dL(-1). PMID- 26354281 TI - Surface characterization and corrosion behavior of calcium phosphate-base composite layer on titanium and its alloys via plasma electrolytic oxidation: A review paper. AB - In recent years, calcium phosphate-base composites, such as hydroxyapatite (HA) and carbonate apatite (CA) have been considered desirable and biocompatible coating layers in clinical and biomedical applications such as implants because of the high resistance of the composites. This review focuses on the effects of voltage, time and electrolytes on a calcium phosphate-base composite layer in case of pure titanium and other biomedical grade titanium alloys via the plasma electrolytic oxidation (PEO) method. Remarkably, these parameters changed the structure, morphology, pH, thickness and crystallinity of the obtained coating for various engineering and biomedical applications. Hence, the structured layer caused improvement of the biocompatibility, corrosion resistance and assignment of extra benefits for Osseo integration. The fabricated layer with a thickness range of 10 to 20 MUm was evaluated for physical, chemical, mechanical and tribological characteristics via XRD, FESEM, EDS, EIS and corrosion analysis respectively, to determine the effects of the applied parameters and various electrolytes on morphology and phase transition. Moreover, it was observed that during PEO, the concentration of calcium, phosphor and titanium shifts upward, which leads to an enhanced bioactivity by altering the thickness. The results confirm that the crystallinity, thickness and contents of composite layer can be changed by applying thermal treatments. The corrosion behavior was investigated via the potentiodynamic polarization test in a body-simulated environment. Here, the optimum corrosion resistance was obtained for the coating process condition at 500 V for 15 min in Ringer solution. This review has been summarized, aiming at the further development of PEO by producing more adequate titanium-base implants along with desired mechanical and biomedical features. PMID- 26354282 TI - Classification, processing and application of hydrogels: A review. AB - This article aims to review the literature concerning the choice of selectivity for hydrogels based on classification, application and processing. Super porous hydrogels (SPHs) and superabsorbent polymers (SAPs) represent an innovative category of recent generation highlighted as an ideal mould system for the study of solution-dependent phenomena. Hydrogels, also termed as smart and/or hungry networks, are currently subject of considerable scientific research due to their potential in hi-tech applications in the biomedical, pharmaceutical, biotechnology, bioseparation, biosensor, agriculture, oil recovery and cosmetics fields. Smart hydrogels display a significant physiochemical change in response to small changes in the surroundings. However, such changes are reversible; therefore, the hydrogels are capable of returning to its initial state after a reaction as soon as the trigger is removed. PMID- 26354284 TI - Design of biocomposite materials for bone tissue regeneration. AB - Several synthetic scaffolds are being developed using polymers, ceramics and their composites to overcome the limitations of auto- and allografts. Polymer ceramic composites appear to be the most promising bone graft substitute since the natural bone itself is a composite of collagen and hydroxyapatite. Ceramics provide strength and osteoconductivity to the scaffold while polymers impart flexibility and resorbability. Natural polymers have an edge over synthetic polymers because of their biocompatibility and biological recognition property. But, very few natural polymer-ceramic composites are available as commercial products, and those few are predominantly based on type I collagen. Disadvantages of using collagen include allergic reactions and pathogen transmission. The commercial products also lack sufficient mechanical properties. This review summarizes the recent developments of biocomposite materials as bone scaffolds to overcome these drawbacks. Their characteristics, in vitro and in vivo performance are discussed with emphasis on their mechanical properties and ways to improve their performance. PMID- 26354286 TI - The refluxing anterior accessory saphenous vein demonstrates similar clinical severity when compared to the refluxing great saphenous vein. AB - OBJECTIVE: To prospectively compare disease severity in subjects with anterior accessory saphenous vein versus great saphenous vein incompetence with an incompetent saphenofemoral junction. METHODS: Data were^ collected from 241 subjects and 290 limbs over a six-month period. These subjects were categorized into three groups with primary venous reflux disease, namely anterior accessory saphenous vein, great saphenous vein, and control. Statistical methods including descriptive statistics, student t-tests, and log linear modeling were employed to compare groups and determine predictive features out of the 41 demographic and disease-specific variables collected. RESULTS: Subjects in the anterior accessory saphenous vein group and those in the great saphenous vein group demonstrate statistically significant differences as compared to the control group with respect to the following disease-specific features: mean VCSS, presence of C2 and C3 disease. The anterior accessory saphenous vein group also showed statistically significant differences in gender compared to both great saphenous vein and control, as well as mean body mass index compared to the control. Log-linear modeling revealed equivalent disease severity when comparing patients with saphenofemoral junction reflux to the great saphenous vein or anterior accessory saphenous vein. CONCLUSIONS: Patterns of reflux from the saphenofemoral junction to either the anterior accessory saphenous vein or great saphenous vein possess similar disease severity and commonly suffer complications of venous stasis. PMID- 26354285 TI - Concomitant high expression of Toll-like receptor (TLR) and B-cell receptor (BCR) signalling molecules has clinical implications in mantle cell lymphoma. AB - Mantle cell lymphoma (MCL) is an aggressive disease with frequent relapse. Targeted therapies against B-cell receptor (BCR) molecules have demonstrated improved outcomes in relapsed cases. However, clinical responses are slow and selective, with failure to attain complete remission in a significant subset of patients. Complex interaction of BCR signal transduction with toll-like receptor (TLR) and other pathways in MCL remains unknown, thus averting progress in development of targeted therapies. We have performed detailed digital quantification of BCR/TLR signalling molecules and their effector pathways in a cohort (n = 81) of MCL patients and correlated these data with overall survival. Hierarchical clustering model based on BCR/TLR genes revealed two distinct (BCRhigh and BCRlow ) subsets of patients (n = 32; 40%) with significant differences in expression (>1.5-fold change; p < 0.05). Higher levels of BTK/SYK/BLNK/CARD11/PLCG signalosome and lower expression of MALT1/BCL10 genes suggested tonic pattern of BCR activation. Amplified expression of TLR6/TLR7/TLR9 was noted in concert with hyper-responsiveness of BCR machinery. MYD88, a key TLR adaptor molecule, was not upregulated in any of these clusters, which may suggest a 'cross-talk' between BCR and TLR pathways. In sync with BCR/TLR signalling, we recorded significantly enhanced expression of genes associated with NF-kB pathway in BCRhigh subset of MCL patients. On univariate analysis, the BCRhigh patients showed a trend towards inferior clinical response to a standardized treatment protocol, compared with the BCRlow group (log rank, p = 0.043). In conclusion, we have identified hyperactive BCR/TLR signalling pathways and their effector downstream targets in a subset of MCL patients and associated it with poor clinical outcomes. Our study provides quantitative evidence at RNA expression level of possible concomitant collaboration between TLR and BCR signalling molecules in MCL. These data will provide further insights for future functional studies and, hence, development of targeted therapies for MCL patients. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26354287 TI - Accuracy of venous thromboembolism assessment and compliance to prophylaxis in a tertiary care center. AB - BACKGROUND: Proper assessment of venous thromboembolism (VTE) risk level in hospitalized patients is vital to providing adequate prophylaxis. Clinical decision support (CDS) tools with electronic medical record (EMR) have been used by institutions to improve assessment and prophylaxis. As such, this study was conducted after implementing such a system to compare admitting service (AS) assessment of VTE risk level to the VTE consult service (CS) assessment. In addition, compliance of ordered prophylaxis based on AS assessment was evaluated. METHODS: At a tertiary care center, we performed a review of randomly selected patients assessed within 18 h of admission for VTE risk over a five-month period. A total of 104 patients were evaluated, four of which were excluded because of VTE presence on admission. Patients were assessed for VTE risk independently, first by the AS, followed by the VTE CS. Prophylaxis orders were then reviewed based on AS assessment compliance to CDS recommendations for prophylaxis based on ACCP guidelines. RESULTS: All 100 patients underwent VTE risk assessment within 18 h from admission. The mean age was 63 years. Comparing AS to CS assessment, 13 patients had incorrect assessments (p < .001). Of these, six patients were under assessed (p = .029), and seven patients were over-assessed (p = .014). Based on AS assessment there were eight patients who had incorrect prophylaxis ordered. Unnecessary exposure to complications due to inappropriate prophylaxis occurred in five patients. CONCLUSION: Despite the use of EMR CDS tools, there continues to be a significant number of patients that are being under-assessed and under prophylaxed for VTE resulting in exposing patients to potential harm. Quality programs need to be instituted to further improve VTE assessment and prophylaxis. PMID- 26354283 TI - When 1+1>2: Nanostructured composites for hard tissue engineering applications. AB - Multicomponent, synergistic and multifunctional nanostructures have taken over the spotlight in the realm of biomedical nanotechnologies. The most prospective materials for bone regeneration today are almost exclusively composites comprising two or more components that compensate for the shortcomings of each one of them alone. This is quite natural in view of the fact that all hard tissues in the human body, except perhaps the tooth enamel, are composite nanostructures. This review article highlights some of the most prospective breakthroughs made in this research direction, with the hard tissues in main focus being those comprising bone, tooth cementum, dentin and enamel. The major obstacles to creating collagen/apatite composites modeled after the structure of bone are mentioned, including the immunogenicity of xenogeneic collagen and continuously failing attempts to replicate the biomineralization process in vitro. Composites comprising a polymeric component and calcium phosphate are discussed in light of their ability to emulate the soft/hard composite structure of bone. Hard tissue engineering composites created using hard material components other than calcium phosphates, including silica, metals and several types of nanotubes, are also discoursed on, alongside additional components deliverable using these materials, such as cells, growth factors, peptides, antibiotics, antiresorptive and anabolic agents, pharmacokinetic conjugates and various cell-specific targeting moieties. It is concluded that a variety of hard tissue structures in the body necessitates a similar variety of biomaterials for their regeneration. The ongoing development of nanocomposites for bone restoration will result in smart, theranostic materials, capable of acting therapeutically in direct feedback with the outcome of in situ disease monitoring at the cellular and subcellular scales. Progress in this research direction is expected to take us to the next generation of biomaterials, designed with the purpose of fulfilling Daedalus' dream - not restoring the tissues, but rather augmenting them. PMID- 26354288 TI - Simple antireflux technique for the cologastric anastomosis: complementary step in retrosternal colon interposition procedure. AB - Gastrocolic reflux is a troublesome symptom causing repeated aspiration or chocking in patients underwent retrosternal colon interposition. Various techniques were described to avoid such complication, however, they entail complicated technique that may jeopardize the viability of the graft or cause obstructing symptoms. A simple antireflux procedure is described here alleviating this problem. Over the last 7 years, 87 patients had gastrocolic antireflux procedure for cologastric anastomosis; 75 patients as a primary procedure (group 1) and 12 patients as a secondary procedure treating symptomatic reflux (group 2). The technique entails the creation of cologastric angle after finishing the cologastric anastomosis by applying three stitches between the colon and the stomach, thus tucking the colon to the stomach for 3-4 cm. Gastrocolic reflux was evaluated clinically and radiologically 3 months postoperatively. In group 1, three cases (4%) suffered symptomatic gastrocolic reflux, and seven cases (9.3%) had radiological asymptomatic mild reflux, while all patients in group 2 had complete alleviation of their symptoms with gastrogram showing no reflux. Gastrocolic reflux can be treated simply by creation of cologastric angle; however, controlled trial is needed to confirm its effectiveness in comparison to other described techniques. PMID- 26354289 TI - Geological and taphonomic context for the new hominin species Homo naledi from the Dinaledi Chamber, South Africa. AB - We describe the physical context of the Dinaledi Chamber within the Rising Star cave, South Africa, which contains the fossils of Homo naledi. Approximately 1550 specimens of hominin remains have been recovered from at least 15 individuals, representing a small portion of the total fossil content. Macro-vertebrate fossils are exclusively H. naledi, and occur within clay-rich sediments derived from in situ weathering, and exogenous clay and silt, which entered the chamber through fractures that prevented passage of coarser-grained material. The chamber was always in the dark zone, and not accessible to non-hominins. Bone taphonomy indicates that hominin individuals reached the chamber complete, with disarticulation occurring during/after deposition. Hominins accumulated over time as older laminated mudstone units and sediment along the cave floor were eroded. Preliminary evidence is consistent with deliberate body disposal in a single location, by a hominin species other than Homo sapiens, at an as-yet unknown date. PMID- 26354290 TI - The many mysteries of Homo naledi. AB - More than 1500 fossils from the Rising Star cave system in South Africa have been assigned to a new human species, Homo naledi, which displays a unique combination of primitive and derived traits throughout the skeleton. PMID- 26354292 TI - Double pigtail for preventing ascending cholangitis after endoscopic ultrasonography-guided choledochoduodenostomy with lumen-apposing metal stent. PMID- 26354291 TI - Homo naledi, a new species of the genus Homo from the Dinaledi Chamber, South Africa. AB - Homo naledi is a previously-unknown species of extinct hominin discovered within the Dinaledi Chamber of the Rising Star cave system, Cradle of Humankind, South Africa. This species is characterized by body mass and stature similar to small bodied human populations but a small endocranial volume similar to australopiths. Cranial morphology of H. naledi is unique, but most similar to early Homo species including Homo erectus, Homo habilis or Homo rudolfensis. While primitive, the dentition is generally small and simple in occlusal morphology. H. naledi has humanlike manipulatory adaptations of the hand and wrist. It also exhibits a humanlike foot and lower limb. These humanlike aspects are contrasted in the postcrania with a more primitive or australopith-like trunk, shoulder, pelvis and proximal femur. Representing at least 15 individuals with most skeletal elements repeated multiple times, this is the largest assemblage of a single species of hominins yet discovered in Africa. PMID- 26354296 TI - Stroke: Part 1. PMID- 26354293 TI - Occurrence of adverse events caused by valganciclovir as pre-emptive therapy for cytomegalovirus infection after allogeneic stem cell transplantation is reduced by low-dose administration. AB - BACKGROUND: Pre-emptive therapy with valganciclovir (VGCV) has become the standard therapy for preventing cytomegalovirus (CMV) infection after allogeneic hematopoietic stem cell transplantation (HSCT). The effectiveness of low-dose VGCV (900 mg per day) has been shown to be equal to that of standard-dose VGCV (900 mg twice daily); however, individualized optimal dosing and toxicity of VGCV have not been reported. METHODS: We conducted a retrospective study to evaluate the optimal dose of VGCV as pre-emptive therapy for preventing CMV infection by comparing the frequency of adverse events (AEs) and clinical efficacy in a low dose VGCV group with those in a standard-dose VGCV group. Thirty-eight patients who were administered VGCV because of CMV antigenemia after HSCT were analyzed. RESULTS: Neutropenia (standard-dose group: 33%, low-dose group: 15%, P = 0.26) and thrombocytopenia (standard-dose group: 39%, low-dose group: 15%, P = 0.14) were frequent AEs of VGCV, and a significantly higher frequency of overall AEs was detected in the standard-dose group than in the low-dose group (P < 0.01). In comparison of dosage based on weight, dosage of VGCV >27 mg/kg was closely related to onset of AEs (P = 0.04). CONCLUSIONS: Low-dose VGCV was not inferior in clinical efficacy, including clearance rate of CMV antigenemia and incidence of consequent CMV disease, to standard-dose VGCV as was previously reported. Initial low-dose VGCV for pre-emptive CMV therapy markedly reduces hematologic toxicity and has clinical efficacy equivalent to that of standard-dose VGCV. It is therefore reasonable for patients, except for noticeably overweight patients, to be given initial low-dose VGCV. PMID- 26354295 TI - A 77-Year-Old Man With Large Vessel Acute Ischemic Stroke. PMID- 26354297 TI - The Erosion of Privacy. PMID- 26354298 TI - Articles That May Change Your Practice: Intubation and Ventilation. PMID- 26354300 TI - REACH Air Medical Services: 100,000 Lives and Counting! PMID- 26354301 TI - Implementing Simulation in Air Medical Training: Integration of Adult Learning Theory. PMID- 26354302 TI - The Evolution of a Safety Culture. PMID- 26354304 TI - Ventilation Monitoring in Severe Pediatric Traumatic Brain Injury at Nontrauma Centers. AB - OBJECTIVE: Pediatric traumatic brain injury (TBI) guidelines should direct patient management. This retrospective study compared ventilation monitoring practices of nontrauma center (NTC) personnel and air medical crews (AMCs) in pediatric patients with severe TBI at NTCs after endotracheal intubation. METHODS: Pediatric patient charts for level I trauma center admissions between 2008 and 2013 with severe TBI were screened. Inclusion criteria included admission Glasgow Coma Scale score <= 8, head Abbreviated Injury Scale score of >= 3, and secure airway initiated or managed at an NTC. RESULTS: A total of 30 patients were evaluated. The median head Abbreviated Injury Scale score was 4, and the trauma center mortality rate was 30%. NTC personnel and AMCs intubated 22 and 8 patients, respectively. AMCs monitored ventilation with much greater regularity (100 vs. 41%, P = .004), used continuous waveform capnography more often (75 vs. 14%, P = .003), and also initiated it quicker (17 vs. 37 minutes, = .001) after intubation. Unmonitored patients from NTC intubations waited on average 72.3 minutes before interfacility transport to the trauma center. CONCLUSIONS: AMCs showed superior ventilation monitoring after intubation in pediatric patients with severe TBI. Ventilation monitoring was not routinely conducted by NTC personnel, signifying areas to improve patient care. PMID- 26354303 TI - Anticoagulation and Non-urgent Commercial Air Travel: A Review of the Literature. PMID- 26354305 TI - Air Medical Curricula in Emergency Medicine Residencies: A National Survey. AB - OBJECTIVE: The aim of this study was to determine if a common air medical curriculum exists among Accreditation Council for Graduate Medical Education (ACGME) emergency medicine (EM) residencies. METHODS: Institutional review board exemption was obtained. A cross-sectional survey study design was used. All ACGME approved EM residencies as of February 2013 were identified, and the program directors were e-mailed a 3-question survey. Descriptive statistics were calculated for each response, and a response bias analysis was completed. RESULTS: All 160 ACGME EM residencies were contacted by e-mail. One hundred six (66%) programs responded. Sixty-nine (65%) of the respondents offered an air medical experience. Only 25 of the 69 (36%) stated that they had a formal air medical curriculum, and 15 programs provided a copy of their curriculum. Protocol education was present in 80% of programs. Safety training was present in 60% of the programs. Financial education was present in 7% of programs. There was no statistically significant difference between responders and nonresponders except for residency class size. CONCLUSION: After 30 years of published articles and position statements calling for standardized air medical resident crew member training, there is still no standardized training program among emergency medicine residencies. PMID- 26354306 TI - Rest, Shift Duration, and Air Medical Crewmember Fatigue. PMID- 26354307 TI - An Unusual Case of Hypotension and Electrocardiographic Changes. PMID- 26354308 TI - A panel data analysis of the probability of childbirth in a Japanese sample: New evidence of the two-child norm. AB - OBJECTIVES: To reveal the conditions that could facilitate childbirth in modern humans, it is necessary to analyze not only cross-sectional surveys but also panel data that track the same person for a long period. In this study, we analyzed factors that would influence the probability of childbirth. METHODS: We analyzed Japanese panel data with a Cox proportional hazard model. Subjects of our analysis were married women and their childbirth records from 2004 to 2009. RESULTS: Contrary to the predictions based on the theory of behavioral ecology, we found no positive relationship between good parental conditions for childcare, such as high income, increase in income, or coresidence with parents (i.e., grandparents of children), and the occurrence of childbirth. We found that the number of existing children had a significant impact on the probability of childbirth. The likelihood of further childbirth by couples with one child was nearly equal to that of childless ones. However, the corresponding likelihood of couples with two children was about five times lower than that of childless ones. CONCLUSIONS: The total fertility rates in modern developed societies are quite low and couples prefer having two children. This trend is known as the two-child norm, but it is a paradoxical phenomenon in terms of fitness maximization. Our result provided new quantitative evidence of this norm. This study revealed that the number of existing children being less than two was one of the factors associated with further childbearing in our Japanese sample. PMID- 26354309 TI - CD3 and CD20 Coexpression in a Case of Canine Cutaneous Epitheliotropic T-Cell Lymphoma (Mycosis Fungoides). AB - A 14-year-old female spayed Dachshund was presented with generalized scaling, erythema, pruritus, poor quality of hair coat, and progressive weight loss. Cutaneous epitheliotropic T-cell lymphoma (CETCL) was suspected. Skin biopsies were suggestive of CETCL. However, immunohistochemistry revealed the presence of numerous CD20+ and CD3+ cells. Clonality assay demonstrated a clonal T-cell receptor gamma rearrangement and a polyclonal IgH gene rearrangement. Double label immunofluorescence confirmed coexpression of CD3 and CD20 by neoplastic cells. By double immunohistochemistry, neoplastic cells were CD3+ and PAX5-. The results are compatible with a CD3+, CD20+ CETCL. Coexpression of CD20 and CD3 has been recognized in peripheral T-cell lymphomas. Although documented in human CETCL, it has not been reported in canine CETCL. The pathogenetic basis of CD20 expression in mycosis fungoides is explored. PMID- 26354310 TI - Bilirubin Encephalopathy in a Domestic Shorthair Cat With Increased Osmotic Fragility and Cholangiohepatitis. AB - A 7-month-old female domestic shorthair cat was diagnosed with chronic regenerative hemolytic anemia characterized by increased osmotic fragility of unknown etiology. At 13 months of age, the cat was evaluated for acute collapse. The cat was icteric with severe hyperbilirubinemia but no hematocrit changes. Severe obtundation and lateral recumbency progressed to tetraparesis and loss of proprioception in all 4 limbs, and a cerebellar or brainstem lesion was suspected. Postmortem examination revealed suppurative cholangiohepatitis and acute neuronal necrosis in the nuclei of the brainstem and cerebellum, consistent with bilirubin encephalopathy. This is the first known occurrence of cholangiohepatitis and bilirubin encephalopathy in an adult cat with chronic hemolytic anemia. Although rare, bilirubin encephalopathy should be considered a possible sequela to hyperbilirubinemia in adult patients. It remains unknown whether increased osmotic fragility was related to the cholangiohepatopathy. PMID- 26354311 TI - Conversations between self and self as Sigmund Freud--A virtual body ownership paradigm for self counselling. AB - When people see a life-sized virtual body (VB) from first person perspective in virtual reality they are likely to have the perceptual illusion that it is their body. Additionally such virtual embodiment can lead to changes in perception, implicit attitudes and behaviour based on attributes of the VB. To date the changes that have been studied are as a result of being embodied in a body representative of particular social groups (e.g., children and other race). In our experiment participants alternately switched between a VB closely resembling themselves where they described a personal problem, and a VB representing Dr Sigmund Freud, from which they offered themselves counselling. Here we show that when the counsellor resembles Freud participants improve their mood, compared to the counsellor being a self-representation. The improvement was greater when the Freud VB moved synchronously with the participant, compared to asynchronously. Synchronous VB movement was associated with a much stronger illusion of ownership over the Freud body. This suggests that this form of embodied perspective taking can lead to sufficient detachment from habitual ways of thinking about personal problems, so as to improve the outcome, and demonstrates the power of virtual body ownership to effect cognitive changes. PMID- 26354312 TI - Postnatal development attunes olfactory bulb mitral cells to high-frequency signaling. AB - Mitral cells (MCs) are a major class of principal neurons in the vertebrate olfactory bulb, conveying odor-evoked activity from the peripheral sensory neurons to olfactory cortex. Previous work has described the development of MC morphology and connectivity during the first few weeks of postnatal development. However, little is known about the postnatal development of MC intrinsic biophysical properties. To understand stimulus encoding in the developing olfactory bulb, we have therefore examined the development of MC intrinsic biophysical properties in acute slices from postnatal day (P)7-P35 mice. Across development, we observed systematic changes in passive membrane properties and action potential waveforms consistent with a developmental increase in sodium and potassium conductances. We further observed developmental decreases in hyperpolarization-evoked membrane potential sag and firing regularity, extending recent links between MC sag heterogeneity and firing patterns. We then applied a novel combination of statistical analyses to examine how the evolution of these intrinsic biophysical properties specifically influenced the representation of fluctuating stimuli by MCs. We found that immature MCs responded to frozen fluctuating stimuli with lower firing rates, lower spike-time reliability, and lower between-cell spike-time correlations than more mature MCs. Analysis of spike-triggered averages revealed that these changes in spike timing were driven by a developmental shift from broad integration of inputs to more selective detection of coincident inputs. Consistent with this shift, generalized linear model fits to MC firing responses demonstrated an enhanced encoding of high frequency stimulus features by mature MCs. PMID- 26354313 TI - Alterations in lower limb multimuscle activation patterns during stair climbing in female total knee arthroplasty patients. AB - Total knee arthroplasty (TKA) patients commonly experience neuromuscular adaptations that may affect stair climbing competence. This study identified multimuscle pattern (MMP) changes in postoperative female TKA patients during stair climbing with a support vector machine (SVM). It was hypothesized that TKA patients adopt temporal and spectral muscle activation characteristics indicative of muscle atrophy and cocontraction strategies. Nineteen female subjects [10 unilateral sex-specific TKAs, 62.2 +/- 8.6 yr, body mass index (BMI) 28.2 +/- 5.4 kg/m(2); 9 healthy control subjects, 61.4 +/- 7.4 yr, BMI 25.6 +/- 2.4 kg/m(2)] were recruited. Surface electromyograms (EMGs) were obtained for seven lower limb muscles of the affected limb of TKA subjects and a randomly assigned limb for control subjects during stair climbing. Stance phase (+/-30%) EMG data were wavelet transformed and normalized to total power. Data across all muscles were combined to form MMPs and analyzed with a SVM. Statistical analysis was performed with binomial tests, independent group t-tests, or independent group Mann-Whitney U-tests in SPSS (P < 0.05). SVM results indicated significantly altered muscle activation patterns in the TKA group for biceps femoris (recognition rate 84.2%), semitendinosus (recognition rate 73.7%), gastrocnemius (recognition rate 68.4%), and tibialis anterior (recognition rate 68.4%). Further analysis identified no significant differences in spectral activation characteristics between groups. Temporal adaptations, indicative of cocontraction strategies, were, however, evident in TKA MMPs. This approach may provide a valuable tool for clinical neuromuscular function assessment and rehabilitation monitoring. PMID- 26354314 TI - Accurate stepping on a narrow path: mechanics, EMG, and motor cortex activity in the cat. AB - How do cats manage to walk so graciously on top of narrow fences or windowsills high above the ground while apparently exerting little effort? In this study we investigated cat full-body mechanics and the activity of limb muscles and motor cortex during walking along a narrow 5-cm path on the ground. We tested the hypotheses that during narrow walking 1) lateral stability would be lower because of the decreased base-of-support area and 2) the motor cortex activity would increase stride-related modulation because of imposed demands on lateral stability and paw placement accuracy. We measured medio-lateral and rostro-caudal dynamic stability derived from the extrapolated center of mass position with respect to the boundaries of the support area. We found that cats were statically stable in the frontal plane during both unconstrained and narrow-path walking. During narrow-path walking, cats walked slightly slower with more adducted limbs, produced smaller lateral forces by hindlimbs, and had elevated muscle activities. Of 174 neurons recorded in cortical layer V, 87% of forelimb-related neurons (from 114) and 90% of hindlimb-related neurons (from 60) had activities during narrow-path walking distinct from unconstrained walking: more often they had a higher mean discharge rate, lower depth of stride-related modulation, and/or longer period of activation during the stride. These activity changes appeared to contribute to control of accurate paw placement in the medio-lateral direction, the width of the stride, rather than to lateral stability control, as the stability demands on narrow-path and unconstrained walking were similar. PMID- 26354315 TI - Theta-rhythmic drive between medial septum and hippocampus in slow-wave sleep and microarousal: a Granger causality analysis. AB - Medial septum (MS) plays a critical role in controlling the electrical activity of the hippocampus (HIPP). In particular, theta-rhythmic burst firing of MS neurons is thought to drive lasting HIPP theta oscillations in rats during waking motor activity and REM sleep. Less is known about MS-HIPP interactions in nontheta states such as non-REM sleep, in which HIPP theta oscillations are absent but theta-rhythmic burst firing in subsets of MS neurons is preserved. The present study used Granger causality (GC) to examine the interaction patterns between MS and HIPP in slow-wave sleep (SWS, a nontheta state) and during its short interruptions called microarousals (a transient theta state). We found that during SWS, while GC revealed a unidirectional MS->HIPP influence over a wide frequency band (2-12 Hz, maximum: ~8 Hz), there was no theta peak in the hippocampal power spectra, indicating a lack of theta activity in HIPP. In contrast, during microarousals, theta peaks were seen in both MS and HIPP power spectra and were accompanied by bidirectional GC with MS->HIPP and HIPP->MS theta drives being of equal magnitude. Thus GC in a nontheta state (SWS) vs. a theta state (microarousal) primarily differed in the level of HIPP->MS. The present findings suggest a modification of our understanding of the role of MS as the theta generator in two regards. First, a MS->HIPP theta drive does not necessarily induce theta field oscillations in the hippocampus, as found in SWS. Second, HIPP theta oscillations entail bidirectional theta-rhythmic interactions between MS and HIPP. PMID- 26354316 TI - Sensitivity of rat inferior colliculus neurons to frequency distributions. AB - Stimulus-specific adaptation refers to a neural response reduction to a repeated stimulus that does not generalize to other stimuli. However, stimulus-specific adaptation appears to be influenced by additional factors. For example, the statistical distribution of tone frequencies has recently been shown to dynamically alter stimulus-specific adaptation in human auditory cortex. The present study investigated whether statistical stimulus distributions also affect stimulus-specific adaptation at an earlier stage of the auditory hierarchy. Neural spiking activity and local field potentials were recorded from inferior colliculus neurons of rats while tones were presented in oddball sequences that formed two different statistical contexts. Each sequence consisted of a repeatedly presented tone (standard) and three rare deviants of different magnitudes (small, moderate, large spectral change). The critical manipulation was the relative probability with which large spectral changes occurred. In one context the probability was high (relative to all deviants), while it was low in the other context. We observed larger responses for deviants compared with standards, confirming previous reports of increased response adaptation for frequently presented tones. Importantly, the statistical context in which tones were presented strongly modulated stimulus-specific adaptation. Physically and probabilistically identical stimuli (moderate deviants) in the two statistical contexts elicited different response magnitudes consistent with neural gain changes and thus neural sensitivity adjustments induced by the spectral range of a stimulus distribution. The data show that already at the level of the inferior colliculus stimulus-specific adaptation is dynamically altered by the statistical context in which stimuli occur. PMID- 26354317 TI - Spatial variability in cortex-muscle coherence investigated with magnetoencephalography and high-density surface electromyography. AB - Cortex-muscle coherence (CMC) reflects coupling between magnetoencephalography (MEG) and surface electromyography (sEMG), being strongest during isometric contraction but absent, for unknown reasons, in some individuals. We used a novel nonmagnetic high-density sEMG (HD-sEMG) electrode grid (36 mm * 12 mm; 60 electrodes separated by 3 mm) to study effects of sEMG recording site, electrode derivation, and rectification on the strength of CMC. Monopolar sEMG from right thenar and 306-channel whole-scalp MEG were recorded from 14 subjects during 4 min isometric thumb abduction. CMC was computed for 60 monopolar, 55 bipolar, and 32 Laplacian HD-sEMG derivations, and two derivations were computed to mimic "macroscopic" monopolar and bipolar sEMG (electrode diameter 9 mm; interelectrode distance 21 mm). With unrectified sEMG, 12 subjects showed statistically significant CMC in 91-95% of the HD-sEMG channels, with maximum coherence at ~25 Hz. CMC was about a fifth stronger for monopolar than bipolar and Laplacian derivations. Monopolar derivations resulted in most uniform CMC distributions across the thenar and in tightest cortical source clusters in the left rolandic hand area. CMC was 19-27% stronger for HD-sEMG than for "macroscopic" monopolar or bipolar derivations. EMG rectification reduced the CMC peak by a quarter, resulted in a more uniformly distributed CMC across the thenar, and provided more tightly clustered cortical sources than unrectifed sEMGs. Moreover, it revealed CMC at ~12 Hz. We conclude that HD-sEMG, especially with monopolar derivation, can facilitate detection of CMC and that individual muscle anatomy cannot explain the high interindividual CMC variability. PMID- 26354318 TI - Tactile orientation perception: an ideal observer analysis of human psychophysical performance in relation to macaque area 3b receptive fields. AB - The ability to resolve the orientation of edges is crucial to daily tactile and sensorimotor function, yet the means by which edge perception occurs is not well understood. Primate cortical area 3b neurons have diverse receptive field (RF) spatial structures that may participate in edge orientation perception. We evaluated five candidate RF models for macaque area 3b neurons, previously recorded while an oriented bar contacted the monkey's fingertip. We used a Bayesian classifier to assign each neuron a best-fit RF structure. We generated predictions for human performance by implementing an ideal observer that optimally decoded stimulus-evoked spike counts in the model neurons. The ideal observer predicted a saturating reduction in bar orientation discrimination threshold with increasing bar length. We tested 24 humans on an automated, precision-controlled bar orientation discrimination task and observed performance consistent with that predicted. We next queried the ideal observer to discover the RF structure and number of cortical neurons that best matched each participant's performance. Human perception was matched with a median of 24 model neurons firing throughout a 1-s period. The 10 lowest-performing participants were fit with RFs lacking inhibitory sidebands, whereas 12 of the 14 higher performing participants were fit with RFs containing inhibitory sidebands. Participants whose discrimination improved as bar length increased to 10 mm were fit with longer RFs; those who performed well on the 2-mm bar, with narrower RFs. These results suggest plausible RF features and computational strategies underlying tactile spatial perception and may have implications for perceptual learning. PMID- 26354319 TI - GnRH suppresses excitability of visual processing neurons in the optic tectum. AB - Animals change their behavior in response to sensory cues in the environment as well as their physiological status. For example, it is generally accepted that their sexual behavior is modulated according to seasonal environmental changes or the individual's maturational/reproductive status, and neuropeptides have been suggested to play important roles in this process. Some behavioral modulation arises from neuropeptide modulation of sensory information processing in the central nervous system, but the neural mechanisms still remain unknown. Here we focused on the neural basis of neuropeptide modulation of visual processing in vertebrates. The terminal nerve neurons that contain gonadotropin-releasing hormone 3 (TN-GnRH3 neurons) are suggested to modulate reproductive behavior and have massive projections to the optic tectum (OT), which plays an important role in visual processing. In the present study, to examine whether GnRH3 modulates retino-tectal neurotransmission in the OT, we analyzed the effect of GnRH3 electrophysiologically and morphologically. We found that field potentials evoked by optic tract fiber stimulation, which represent retino-tectal neurotransmission, were modulated postsynaptically by GnRH3. Whole cell recording from postsynaptic neurons in the retino-tectal pathway suggested that GnRH3 activates large-conductance Ca(2+)-activated K(+) (BK) channels and thereby suppresses membrane excitability. Furthermore, our improved morphological analysis using fluorescently labeled GnRH peptides showed that GnRH receptors are localized mainly around the cell bodies of postsynaptic neurons. Our results indicate that TN-GnRH3 neurons modulate retino-tectal neurotransmission by suppressing the excitability of projection neurons in the OT, which underlies the neuromodulation of behaviorally relevant visual information processing by the neuropeptide GnRH3. PMID- 26354321 TI - Suppressing Nitrite-oxidizing Bacteria Growth to Achieve Nitrogen Removal from Domestic Wastewater via Anammox Using Intermittent Aeration with Low Dissolved Oxygen. AB - Achieving nitrogen removal from domestic wastewater using anaerobic ammonium oxidation (anammox) has the potential to make wastewater treatment energy-neutral or even energy-positive. The challenge is to suppress the growth of nitrite oxidizing bacteria (NOB). This study presents a promising method based on intermittent aeration with low dissolved oxygen to limit NOB growth, thereby providing an advantage to anammox bacteria to form a partnership with the ammonium-oxidizing bacteria (AOB). The results showed that NOB was successfully suppressed using that method, with the relative abundance of NOB maintained between 2.0-2.6%, based on Fluorescent in-situ Hybridization. Nitrogen could be effectively removed from domestic wastewater with anammox at a temperature above 20 degrees C, with an effluent total nitrogen (TN) concentration of 6.6 +/- 2.7 mg/L, while the influent TN and soluble chemical oxygen demand were 62.6 +/- 3.1 mg/L and 88.0 +/- 8.1 mg/L, respectively. PMID- 26354320 TI - Ischemic injury suppresses hypoxia-induced electrographic seizures and the background EEG in a rat model of perinatal hypoxic-ischemic encephalopathy. AB - The relationship among neonatal seizures, abnormalities of the electroencephalogram (EEG), brain injury, and long-term neurological outcome (e.g., epilepsy) remains controversial. The effects of hypoxia alone (Ha) and hypoxia-ischemia (HI) were studied in neonatal rats at postnatal day 7; both models generate EEG seizures during the 2-h hypoxia treatment, but only HI causes an infarct with severe neuronal degeneration. Single-channel, differential recordings of acute EEG seizures and background suppression were recorded with a novel miniature telemetry device during the hypoxia treatment and analyzed quantitatively. The waveforms of electrographic seizures (and their behavioral correlates) appeared virtually identical in both models and were identified as discrete events with high power in the traditional delta (0.1-4 Hz) and/or alpha (8-12 Hz) bands. Although the EEG patterns during seizures were similar in Ha- and HI-treated animals at the beginning of the hypoxic insult, Ha caused a more severe electrographic seizure profile than HI near the end. Analyses of power spectral density and seizure frequency profiles indicated that the electrographic seizures progressively increased during the 2-h Ha treatment, while HI led to a progressive decrease in the seizures with significant suppression of the EEG background. These data show that 1) the hypoxia component of these two models drives the seizures; 2) the seizures during Ha are substantially more robust than those during HI, possibly because ongoing neuronal damage blunts the electrographic activity; and 3) a progressive decrease in background EEG, rather than the presence of electrographic seizures, indicates neuronal degeneration during perinatal HI. PMID- 26354322 TI - Fibromyalgia syndrome and cognitive dysfunction in elderly: a case series. AB - AIM: Fibromyalgia syndrome (FMS) is an extremely rare complication of neurocognitive disorders (NCDs). We experienced seven such cases, and we discuss their clinical manifestation and pathomechanisms. METHODS: Seven patients with FMS as a complication of NCD were enrolled. We used the patients' medical records to identify clinical manifestations and obtain experimental data, such as pain questionnaire scores, cognitive tests, genetics and radiological imaging of the brain. RESULTS: The seven patients were clinically diagnosed with frontotemporal NCD (n = 3) or Alzheimer's disease (n = 4). No patient presented with any organic disorder that would explain their chronic pain. Through their courses, they experienced refractory widespread pain continuously despite analgesics. Brain magnetic resonance imaging revealed moderate or severe atrophic changes in the temporal lobes and hippocampus. Three-dimensional stereotactic surface projection (3D-SSP) analysis of brain single photon emission computed tomography (SPECT), indicated severe hypoperfusion on the right side of the medial temporal lobe, both sides of the anterior corpus callosum, anterior cingulate gyrus, and primary sensory area. Genetic analysis uncovered no pathogenic mutations. CONCLUSIONS: Neurodegenerative disorders are rarely complicated by FMS, which is associated with relatively severe pain. Central sensitization may be a possible risk factor of widespread pain in elderly patients with NCD. PMID- 26354323 TI - Effect of the Concentration of Cytolytic Protein Cyt2Aa2 on the Binding Mechanism on Lipid Bilayers Studied by QCM-D and AFM. AB - Bacillus thuringiensis is known by its insecticidal property. The insecticidal proteins are produced at different growth stages, including the cytolytic protein (Cyt2Aa2), which is a bioinsecticide and an antimicrobial protein. However, the binding mechanism (and the interaction) of Cyt2Aa2 on lipid bilayers is still unclear. In this work, we have used quartz crystal microbalance with dissipation (QCM-D) and atomic force microscopy (AFM) to investigate the interaction between Cyt2Aa2 protein and (cholesterol-)lipid bilayers. We have found that the binding mechanism is concentration dependent. While at 10 MUg/mL, Cyt2Aa2 binds slowly on the lipid bilayer forming a compliance protein/lipid layer with aggregates, at higher protein concentrations (100 MUg/mL), the binding is fast, and the protein/lipid layer is more rigid including holes (of about a lipid bilayer thickness) in its structure. Our study suggests that the protein/lipid bilayer binding mechanism seems to be carpet-like at low protein concentrations and pore forming-like at high protein concentrations. PMID- 26354325 TI - Karyotypic diversity of the armoured catfish genus Hypostomus (Siluriformes: Loricariidae) in the context of its occurrence and distribution. AB - This study taxonomically reviewed the specimens studied by Artoni & Bertollo (1996) and assimilated species of Hypostomus into three groups according to their cytogenetic characteristics, vagility and occurrence environments. PMID- 26354324 TI - EGFR Exon 18 Mutations in East Asian Patients with Lung Adenocarcinomas: A Comprehensive Investigation of Prevalence, Clinicopathologic Characteristics and Prognosis. AB - Our aim was to investigate the clinical and pathologic characteristics of the epidermal growth factor receptor (EGFR) exon 18 mutations in East Asian lung adenocarcinomas patients. A total of 1,201 lung adenocarcinomas were analyzed for mutation in EGFR. Clinical and pathologic characteristics of patients with EGFR exon 18 mutations were compared with those who harbored classic activating mutations (exon 19 deletions and the L858R point mutation). The mutations in EGFR exon 18 were observed in 2.8% of 1,201 lung adenocarcinomas and 4.6% of patients with EGFR mutations. Patients with a single EGFR exon of 18 mutations had a worse overall survival than those harboring the complex EGFR exon of 18 mutations (p = 0.002) or those with classic activating mutations (p = 0.014). Four of five patients with EGFR exon 18 mutations showed objective response to the EGFR-TKI therapies after disease recurrence. Our results demonstrated that single EGFR exon 18 mutations may be an indicator of poor prognosis compared with complex EGFR exon 18 mutations or classic mutations. Furthermore, the results of the current study will be helpful for decision-making in the treatment of patients with EGFR exon 18 mutations. PMID- 26354327 TI - Intraoperative ultrasound: a review on its role in liver surgery for primitive and metastatic tumors. AB - Intra-operative ultrasound is an invaluable tool in hepatic surgery, either for restaging either as a guidance during resection of liver neoplasms. Nowadays, intraoperative ultrasound is still considered the most accurate diagnostic technique for detecting focal liver lesions in both hepatocellular carcinoma and colorectal liver metastases, which represent the most frequent indication for liver resection. Moreover, the use of ultrasound guidance is mandatory for planning the surgical strategy, deciding the exact resection plane and during the parenchymal transection, in order to respect the surrounding vessels and biliary structures. Every surgical procedure performed on the liver is strictly dependent from the knowledge of the liver anatomy and from the ultrasounds; definitely in liver surgery the ultrasounds represent the link between the surgical anatomy and the surgical intervention. To maximize the benefit, intraoperative ultrasound should be carried out by the surgeon himself in the perspective of surgical guidance. Here is presented an updated and extensive review of the role of ultrasounds in liver surgery, describing and analyzing the possible applications of this invaluable tool from the surgeon's point of view. Technical aspects, principles of intraoperative re-staging and ultrasound-guided liver resection, application and possible advantages of laparoscopic ultrasound and new perspective in intraoperative study of the liver are discussed. PMID- 26354326 TI - Epidemiology of acute cholecystitis and its treatment in Bergamo District, Northern Italy. AB - BACKGROUND: Acute calcolous cholecystitis (ACC) is a very common pathology in western countries. The aim of our work was to assess the epidemiology of ACC and its treatment in Bergamo, a northern Italy province, during the last seventeen years. METHODS: A restrospective analysis, covering 1997 to 2013, was performed based on the administrative register of the province Health System. Only patients admitted for ACC were selected. From 1997 to 2013 were collected 8959 cases of ACC, mean age was 61.28, 51.5% were male. RESULTS: The incidence of ACC was 48/100.000 per year; the operation rate was 66%. Overall mortality was 0.7%, mean hospitalization time was 9.7 days. The treatment of ACC in Bergamo Province seemed to be acceptable and comparable to literature results. Over the last years, laparoscopy has become the standard treatment. CONCLUSIONS: This study outlined some criticisms on the selection's methodology sourcing data from administrative registers, raising questions about truthfulness of results and usefulness for health policy issues. PMID- 26354328 TI - Endoscopic ultrasound in the preoperative staging of gastric cancer: key messages for surgeons. AB - Gastric cancer (GC) remains a frequent and important cause of cancer mortality worldwide. Many factors affect the prognosis of GC, but invasion and metastasis are the leading causes of death. Due to the various stage-oriented therapies available, after the diagnosis of GC it is important to determine the staging preoperatively in order to choose the appropriate management. GC staging is the workhorse of endoscopic ultrasound (EUS). EUS can distinguish the different wall layers of the gastrointestinal tract as well as assess regional lymph nodes. Furthermore, samples of suspicious lesions or lymph nodes can be obtained by means of EUS-guided fine-needle aspiration (EUS-FNA). In this narrative review, we highlight the current status of the usefulness of EUS for GC staging, with focus on early GC that still remains a diagnostic and therapeutic challenge. In particular, the possibility to ameliorate the accuracy of EUS, in this context, by using instruments with increased ultrasound frequency is emphasized. PMID- 26354329 TI - Intimacy and a deadly feud: the interplay of autophagy and apoptosis mediated by amino acids. AB - Autophagy (i.e., "self-eating") and apoptosis (i.e., type I programmed cell death) are essential and intimately involved in molecular, cellular, and whole body homeostasis in humans and animals. Autophagy has been categorized as a mechanism of intracellular degradation, recycling, defense, and survival. To date, three types of autophagy have been identified: macroautophagy, microautophagy, and chaperone-mediated autophagy. Recent discoveries strongly suggest that macroautophagy also modulates type II programmed cell death under specific circumstances. Autophagy and apoptosis are fundamentally distinct processes, but are interconnected by common stress initiators and intermediate regulators. During the past two decades, the role of amino acid metabolism and signaling in the regulation of apoptosis and autophagy has been intensively studied. In this review, we summarize recent advances in our understanding of the molecular mechanisms that regulate both autophagy and apoptosis in the context of amino acid signaling. PMID- 26354330 TI - Molecular mechanisms underlying endometriosis pathogenesis revealed by bioinformatics analysis of microarray data. AB - OBJECTIVE: To identify differentially expressed genes (DEGs) in endometriosis and further analyze molecular mechanisms implicated in disease pathogenesis. MATERIALS AND METHODS: Gene expression data (ID: GSE7846) of human endometrial endothelial cells (HEECs) collected from eutopic endometria tissue of patients with and without endometriosis were downloaded from Gene Expression Omnibus. DEGs were screened using Limma package, followed by enrichment analysis using clusterProfiler package in R. Thereafter, protein-protein interactions (PPIs) were analyzed using STRING (Search Tool for the Retrieval of Interacting Genes) database and visualized by Cytoscape software. Meanwhile, transcription factors were screened from the DEGs based on TRANSFA database, followed by construction of regulatory network using Cytoscape. RESULTS: A total of 2255 up- and 408 down regulated genes were identified in endometriosis patients as compared with control patients. Those DEGs were predominantly enriched in focal adhesion (e.g., FN1, EGF, FYN, EGFR, RAC1, CCND1 and JUN), regulation of actin cytoskeleton (e.g., FN1, EGF, EGFR, RAC1 and JUN) and MAPK signaling pathway (e.g., EGF, EGFR, RAC1, JUN, TGFB1 and MYC). Importantly, EGF, EGFR, JUN, FN1, RAC1, TGFB1, CCND1 and FYN were hub nodes in the PPI network. Additionally, TGFB1, SMAD1 and SMAD4 showed up-regulation in TGFB signaling pathway. Transcription factor MYC had a regulatory effect on the most DEGs, including TGFB1, RAC1 and CCND1. CONCLUSIONS: Focal adhesion, regulation of actin cytoskeleton, MAPK and TGFB/SMAD signaling pathway may be important molecular mechanism underlying the pathogenesis of endometriosis. PMID- 26354331 TI - Therapeutic intervention based on circulating tumor cell phenotype in metastatic breast cancer: concept of the DETECT study program. AB - PURPOSE: The aim of the ongoing DETECT study program is to evaluate therapeutic intervention based on phenotypes of circulating tumor cells (CTC) in patients with metastatic breast cancer (MBC). Currently (as of July 2015) more than half of the projected about 2000 patients with MBC have already been screened for CTC. METHODS: Women with HER2-negative primary tumor and presence of CTC are recruited into different DETECT trials according to the HER2-phenotype of CTC. Patients with HER2-positive CTC are randomized to treatment with physicians' choice therapy (standard chemo- or endocrine therapy) with or without additional HER2 targeted therapy with lapatinib in the DETECT III trial. In DETECT IVa, postmenopausal patients with hormone-receptor positive primary cancer and HER2 negative CTC receive everolimus and standard endocrine therapy. For women with HER2-negative CTC and triple negative MBC or hormone-receptor positive tumor and indication for chemotherapy, a treatment with eribulin is offered (DETECT IVb). The clinical efficacy is investigated by CTC-Clearance and progression-free survival (PFS). The DETECT V/CHEVENDO trial extends the DETECT study program for women with HER2-positive and hormone-receptor positive MBC. The primary objective of this trial is to compare safety and quality of life (QoL) as assessed by the occurrence of adverse events in patients treated with dual (trastuzumab plus pertuzumab) HER2-targeted therapy plus either endocrine or chemotherapy. The translational research projects of the DETECT study program focus on further molecular characterization of CTC and evaluation of markers for their suitability to predict treatment response and to facilitate the development of more personalized treatment options. PMID- 26354332 TI - Use of Femoral Nerve Blocks to Manage Hip Fracture Pain among Older Adults in the Emergency Department: A Systematic Review. AB - OBJECTIVE: Hip fractures are a common source of acute pain amongst the frail elderly. One potential technique to adequately manage pain in this population is the femoral nerve block. The objective of this systematic review was to provide updated evidence for the use of femoral nerve blocks as a pain management technique for older hip fracture patients in the emergency department (ED). Data Sources Searches of Medline, EMBASE, and the Cochrane Central Register of Controlled Trials were conducted between December 2010 and May 2014. The reference list of a previous systematic review was also searched. Study Selection We included randomized control trials examining the use of femoral nerve blocks in the ED among older adults (65 years of age or older) with acute hip fracture. Data Extraction Among 93 citations reviewed, seven trials were included. Four studies employed a single femoral nerve block, while three studies employed continuous (catheter-placed) femoral blocks. All but one of the studies were found to have a high risk of bias. Data Synthesis All studies reported reductions in pain intensity with femoral nerve blocks. All but one study reported decreased rescue analgesia requirements. There were no adverse effects found to be associated with the femoral block procedure; rather, two studies found a decreased risk of adverse events such as respiratory and cardiac complications. CONCLUSIONS: Femoral nerve blocks appear to have benefits both in terms of decreasing the pain experienced by older patients, as well as limiting the amount of systemic opioids administered to this population. PMID- 26354333 TI - Evolution of Public Health in Asia Pacific. PMID- 26354334 TI - A Risk Score to Predict Hypertension in Primary Care Settings in Rural India. AB - We used the data of 297 participants (15-64 years old) from a cohort study (2003 2010) who were free from hypertension at baseline, to develop a risk score to predict hypertension by primary health care workers in rural India. Age >=35 years, current smoking, prehypertension, and central obesity were significantly associated with incident hypertension. The optimal cutoff value of >=3 had a sensitivity of 78.6%, specificity of 65.2%, positive predictive value of 41.1%, and negative predictive value of 90.8%. The area under the receiver operating characteristic curve of the risk score was 0.802 (95% confidence interval = 0.748 0.856). This simple and easy to administer risk score could be used to predict hypertension in primary care settings in rural India. PMID- 26354335 TI - Caulobacter flavus sp. nov., a stalked bacterium isolated from rhizosphere soil. AB - A Gram-stain-negative, aerobic, yellow-pigmented and rod-shaped bacterium with a single polar flagellum or a stalk, designated strain RHGG3T, was isolated from rhizosphere soil of cultivated watermelon (Citrullus lanatus) collected from Hefei, China. Optimal growth of strain RHGG3T was observed at pH 7.0 and 28-30 degrees C. Cells were catalase-positive and oxidase-negative. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain RHGG3T belonged to the genus Caulobacter and showed the highest 16S rRNA gene sequence similarities to Caulobacter segnis ATCC 21756T (98.6 %), Caulobacter vibrioides CB51T (98.3 %) and Caulobacter henricii ATCC 15253T (97.2 %). The G+C content of the genomic DNA was 70 mol%. Strain RHGG3T contained Q-10 as the sole ubiquinone and the major fatty acids (>8 %) were 11-methyl C18 : 1omega7c, C18 : 1omega7c, C16 : 0, C15 : 0 and summed feature 3 (C16 : 1omega7c and/or iso-C15 : 0 2-OH). The polar lipids were various unknown glycolipids, phosphatidylglycerol and phosphoglycolipids. DNA-DNA relatedness of strain RHGG3T to type strains of the most closely related species (Caulobacter segnis ATCC 21756T, Caulobacter vibrioides DSM 4738 and Caulobacter henricii ATCC 15253T) was 32.4-40.9 %. Based on polyphasic taxonomy analysis (phylogenetic, unique phenotypic traits, chemotaxonomic and DNA-DNA hybridizations), strain RHGG3T represents a novel species of the genus Caulobacter, for which the name Caulobacter flavus sp. nov. is proposed. The type strain is RHGG3T ( = CGMCC 1.15093T = KCTC 42581T = JCM 30763T). PMID- 26354336 TI - Stories as Gift: Patient Narratives and the Development of Empathy. AB - Critical thought and assessment of medical, emotional, and social problems faced by patients is central to genetic counselor training and development. However, primary emphasis on these critical problem-solving approaches can interfere with the development of empathic listening skills. Using a narrative medicine approach, I describe how learning to reframe one patient's story of healing as a gift allowed me to become a more open and empathic listener. Ultimately, the empathy and understanding that I learned from this patient's narrative added to what previous patients had taught me and helped me assist other patients (and myself) in identifying and nurturing healing narratives for people coping with illness and grief. The approach presented here emphasizes the importance of recognizing patients as valuable teachers in the development of higher-level empathy skills. PMID- 26354337 TI - Impact of Genetic Counseling in Women with a Family History of Breast Cancer in Italy. AB - As the impact of breast cancer (BC) risk assessment in asymptomatic women with a family history of BC had never been explored in Italy, we performed a study on a retrospective series of women who had undergone BC risk assessment. To this aim, a semi-structured telephone interview was administered to 82 women. Most participants considered the information received as clear (96.2 %) and helpful (76.8 %). Thirty-eight (46.3 %) stated that their perceived risk of BC had changed after the counseling: for 40.2 % it had decreased, for 6.1 % increased; however, women highly overestimating their risk at the baseline (>= 4-fold) failed to show improvements in risk perception accuracy. Sixty-six women (80.5 %) stated they had followed the recommended surveillance, while 19.5 % had not, mainly due to difficulties in arranging examinations. Most women (89.0 %) had shared the information with their relatives, with 57.3 % reporting other family members had undertaken the recommended surveillance. BC risk assessment was associated with high rates of satisfaction and had a favorable impact on risk perception in a subgroup of women. The impact on surveillance adhesion extended to relatives. Organized programs for identification and surveillance may help identify a larger fraction of at-risk women and overcome the reported difficulties in arranging surveillance. PMID- 26354338 TI - Genetic Counselors' Perspectives and Practices Regarding Expanded Carrier Screening after Initial Clinical Availability. AB - Expanded carrier screening (ECS), introduced in 2009, identifies carriers for dozens or hundreds of recessive diseases. At the time of its introduction into clinical use, perspectives of the genetic counseling community regarding ECS were unknown. We conducted a survey in early 2012 of GCs and report the results here. They represent a snapshot of opinions and usage at that time, providing a baseline for comparison as the technology continues to evolve and as usage increases. The survey assessed personal perspectives, opinions on clinical implementation and clinical utilization of ECS. The sample included 337 GCs of varying clinical fields, of whom 150 reported practicing in reproductive settings. Our findings demonstrate that, at the time, GCs indicated general agreement with ECS as a concept - for example, most GCs agreed that carrier screening should address diseases outside of current guidelines and also indicated personal interest in electing ECS. There were also disagreements or concerns expressed regarding appropriate pre- and post-test counseling (e.g., the content and delivery mode of adequate informed consent) and practical implementation (e.g., the amount of time available for follow-up care). This was the first quantitative study of a large number of GCs and it revealed initial overall support for ECS among the GC profession. The authors plan to re administer a similar survey, which may reveal changes in opinions and/or utilization over time. A follow up survey would also allow further exploration of questions uncovered by these data. PMID- 26354339 TI - Challenges of Pre- and Post-Test Counseling for Orthodox Jewish Individuals in the Premarital Phase. AB - The Jewish community has traditionally taken ownership of its health, and has taken great strides to raise awareness about genetic issues that affect the community, such as Tay-Sachs disease and Hereditary Breast and Ovarian Cancer syndrome. Thanks in part to these heightened awareness efforts, many Orthodox Jewish individuals are now using genetics services as they begin to plan their families. Due to unique cultural and religious beliefs and perceptions, the Orthodox Jewish patients who seek genetic counseling face many barriers to a successful counseling session, and often seek the guidance of programs such as the Program for Jewish Genetic Health (PJGH). In this article, we present clinical vignettes from the PJGH's clinical affiliate, the Reproductive Genetics practice at the Montefiore Medical Center. These cases highlight unique features of contemporary premarital counseling and screening within the Orthodox Jewish Community, including concerns surrounding stigma, disclosure, "marriageability," the use of reproductive technologies, and the desire to include a third party in decision making. Our vignettes demonstrate the importance of culturally-sensitive counseling. We provide strategies and points to consider when addressing the challenges of pre- and post-test counseling as it relates to genetic testing in this population. PMID- 26354340 TI - How rods respond to single photons: Key adaptations of a G-protein cascade that enable vision at the physical limit of perception. AB - Rod photoreceptors are among the most sensitive light detectors in nature. They achieve their remarkable sensitivity across a wide variety of species through a number of essential adaptations: a specialized cellular geometry, a G-protein cascade with an unusually stable receptor molecule, a low-noise transduction mechanism, a nearly perfect effector enzyme, and highly evolved mechanisms of feedback control and receptor deactivation. Practically any change in protein expression, enzyme activity, or feedback control can be shown to impair photon detection, either by decreasing sensitivity or signal-to-noise ratio, or by reducing temporal resolution. Comparison of mammals to amphibians suggests that rod outer-segment morphology and the molecules and mechanism of transduction may have evolved together to optimize light sensitivity in darkness, which culminates in the extraordinary ability of these cells to respond to single photons at the ultimate limit of visual perception. PMID- 26354341 TI - Cardiac Nerve Growth Factor Overexpression Induces Bone Marrow-derived Progenitor Cells Mobilization and Homing to the Infarcted Heart. AB - Reparative response by bone marrow (BM)-derived progenitor cells (PCs) to ischemia is a multistep process that comprises the detachment from the BM endosteal niche through activation of osteoclasts and proteolytic enzymes (such as matrix metalloproteinases (MMPs)), mobilization to the circulation, and homing to the injured tissue. We previously showed that intramyocardial nerve growth factor gene transfer (NGF-GT) promotes cardiac repair following myocardial infarction (MI) in mice. Here, we investigate the impact of cardiac NGF-GT on postinfarction BM-derived PCs mobilization and homing at different time points after adenovirus-mediated NGF-GT in mice. Immunohistochemistry and flow cytometry newly illustrate the temporal profile of osteoclast and activation of MMP9, PCs expansion in the BM, and liberation/homing to the injured myocardium. NGF-GT amplified these responses and increased the BM levels of active osteoclasts and MMP9, which were not observed in MMP9-deficient mice. Taken together, our results suggest a novel role for NGF in BM-derived PCs mobilization/homing following MI. PMID- 26354343 TI - Adverse prognostic impact of bone marrow microvessel density in multiple myeloma. AB - BACKGROUND: Angiogenesis is important for the proliferation and survival of multiple myeloma (MM) cells. Bone marrow (BM) microvessel density (MVD) is a useful marker of angiogenesis and is determined by immunohistochemical staining with anti-CD34 antibody. This study investigated the prognostic impact of MVD and demonstrated the relationship between MVD and previously mentioned prognostic factors in patients with MM. METHODS: The study included 107 patients with MM. MVD was assessed at initial diagnosis in a blinded manner by two hematopathologists who examined three CD34-positive hot spots per patient and counted the number of vessels in BM samples. Patients were divided into three groups according to MVD tertiles. Cumulative progression-free survival (PFS) and overall survival (OS) curves, calculated by using Kaplan-Meier method, were compared among the three groups. Prognostic impact of MVD was assessed by calculating Cox proportional hazard ratio (HR). RESULTS: Median MVDs in the three groups were 16.8, 33.9, and 54.7. MVDs were correlated with other prognostic factors, including beta2-microglobulin concentration, plasma cell percentage in the BM, and cancer stage according to the International Staging System. Multivariate Cox regression analysis showed that high MVD was an independent predictor of PFS (HR=2.57; 95% confidence interval, 1.22-5.42; P=0.013). PFS was significantly lower in the high MVD group than in the low MVD group (P=0.025). However, no difference was observed in the OS (P=0.428). CONCLUSIONS: Increased BM MVD is a marker of poor prognosis in patients newly diagnosed with MM. BM MVD should be assessed at the initial diagnosis of MM. PMID- 26354342 TI - Clinical Improvement of Alpha-mannosidosis Cat Following a Single Cisterna Magna Infusion of AAV1. AB - Lysosomal storage diseases (LSDs) are debilitating neurometabolic disorders for most of which long-term effective therapies have not been developed. Gene therapy is a potential treatment but a critical barrier to treating the brain is the need for global correction. We tested the efficacy of cisterna magna infusion of adeno associated virus type 1 (AAV1) expressing feline alpha-mannosidase gene in the postsymptomatic alpha-mannosidosis (AMD) cat, a homologue of the human disease. Lysosomal alpha-mannosidase (MANB) activity in the cerebrospinal fluid (CSF) and serum were increased above the control values in untreated AMD cats. Clinical neurological signs were delayed in onset and reduced in severity. The lifespan of the treated cats was significantly extended. Postmortem histopathology showed resolution of lysosomal storage lesions throughout the brain. MANB activity in brain tissue was significantly above the levels of untreated tissues. The results demonstrate that a single cisterna magna injection of AAV1 into the CSF can mediate widespread neuronal transduction of the brain and meaningful clinical improvement. Thus, cisterna magna gene delivery by AAV1 appears to be a viable strategy for treatment of the whole brain in AMD and should be applicable to many of the neurotropic LSDs as well as other neurogenetic disorders. PMID- 26354344 TI - Soluble ST2 has a prognostic role in patients with suspected sepsis. AB - BACKGROUND: Soluble suppression of tumorigenicity 2 (sST2) has emerged as a novel biomarker for heart failure, and serum sST2 concentrations could be increased in inflammatory diseases. We explored whether sST2 is related to cardiac dysfunction/failure and has a prognostic role in patients with suspected sepsis. METHODS: In a total of 397 patients with suspected sepsis, sST2 concentrations were measured by using the Presage ST2 Assay (Critical Diagnostics, USA). sST2 concentrations were analyzed according to procalcitonin (PCT) concentrations, cardiovascular subscores of the sepsis-related organ failure assessment (SOFA) score, and clinical outcomes. RESULTS: sST2 concentrations were increased significantly according to the five groups of PCT concentrations and cardiovascular subscores of the SOFA score (P<0.000001 and P=0.036, respectively). In-hospital mortality was significantly higher among patients with sST2 concentrations above 35 ng/mL (P=0.0213) and among patients with increased concentrations of both sST2 and PCT (P=0.0028). CONCLUSIONS: sST2 seems to be related to both cardiac dysfunction/failure and severity in sepsis. Measurement of sST2 and PCT in combination would be useful for risk stratification and prognosis prediction in patients with suspected sepsis. PMID- 26354345 TI - Dried blood spot testing for seven steroids using liquid chromatography-tandem mass spectrometry with reference interval determination in the Korean population. AB - BACKGROUND: Conventional screening for congenital adrenal hyperplasia (CAH) using immunoassays generates a large number of false-positive results. A more specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been introduced to minimize unnecessary follow-ups. However, because of limited data on its use in the Korean population, LC-MS/MS has not yet been incorporated into newborn screening programs in this region. The present study aims to develop and validate an LC-MS/MS method for the simultaneous determination of seven steroids in dried blood spots (DBS) for CAH screening, and to define age-specific reference intervals in the Korean population. METHODS: We developed and validated an LC-MS/MS method to determine the reference intervals of cortisol, 17 hydroxyprogesterone, 11-deoxycortisol, 21-deoxycortisol, androstenedione, corticosterone, and 11-deoxycorticosterone simultaneously in 453 DBS samples. The samples were from Korean subjects stratified by age group (78 full-term neonates, 76 premature neonates, 89 children, and 100 adults). RESULTS: The accuracy, precision, matrix effects, and extraction recovery were satisfactory for all the steroids at three concentrations; values of intra- and inter-day precision coefficients of variance, bias, and recovery were 0.7-7.7%, -1.5-9.8%, and 49.3 97.5%, respectively. The linearity range was 1-100 ng/mL for cortisol and 0.5-50 ng/mL for other steroids (R2>0.99). The reference intervals were in agreement with the previous reports. CONCLUSIONS: This LC-MS/MS method and the reference intervals validated in the Korean population can be successfully applied to analyze seven steroids in DBS for the diagnosis of CAH. PMID- 26354346 TI - Hypertriglyceridemia is a major factor associated with elevated levels of small dense LDL cholesterol in patients with metabolic syndrome. AB - BACKGROUND: We aimed to determine the major contributing component of metabolic syndrome (MetS) that results in an elevated small dense LDL cholesterol (sdLDL-C) concentration and sdLDL-C/LDL-C ratio. METHODS: Four hundred and forty-seven subjects (225 men; 222 women) with MetS were randomly selected from the Korean Metabolic Syndrome Research Initiatives-Seoul cohort study. Age- and sex-matched healthy controls (181 men; 179 women) were also randomly selected from the same cohort. RESULTS: A comparison of the median values of the sdLDL-C concentration between subgroups, divided according to whether subjects met or did not meet the criteria for each MetS component in patients with MetS, revealed a significant difference in the sdLDL-C concentration only between subgroups divided according to whether subjects met or did not meet the triglyceride (TG) criteria (P<0.05 for each gender). The TG level showed a good correlation with sdLDL-C concentration (correlation coefficients [r]=0.543 for men; 0.653 for women) and the sdLDL-C/LDL-C ratio (r=0.789 for men; 0.745 for women). Multiple linear regression analyses conducted for the MetS group concordantly identified TG as one of the most significant contributors to sdLDL-C concentration (beta=0.1747+/ 0.0105, P<0.0001) and the sdLDL-C/LDL-C ratio (beta=6.9518+/-0.3011, P<0.0001). CONCLUSIONS: Among five MetS components, only the abnormal TG level was a differentiating factor for sdLDL-C concentration and sdLDL-C/LDL-C ratio. These results were reproducible in both genders, with or without MetS. PMID- 26354347 TI - Distribution of beta-lactamase genes among carbapenem-resistant Klebsiella pneumoniae strains isolated from patients in Turkey. AB - BACKGROUND: The emergence of carbapenem-resistant Klebsiella pneumoniae poses a serious problem to antibiotic management. We investigated the beta-lactamases in a group of carbapenem-resistant K. pneumoniae clinical isolates from Turkey. METHODS: Thirty-seven strains of K. pneumoniae isolated from various clinical specimens were analyzed by antimicrobial susceptibility testing, PCR for the detection of beta-lactamase genes, DNA sequencing, and repetitive extragenic palindronic (REP)-PCR analysis. RESULTS: All 37 isolates were resistant to ampicillin, ampicillin/sulbactam, piperacillin, piperacillin/tazobactam, ceftazidime, cefoperazone/sulbactam, cefepime, imipenem, and meropenem. The lowest resistance rates were observed for colistin (2.7%), tigecycline (11%), and amikacin (19%). According to PCR and sequencing results, 98% (36/37) of strains carried at least one carbapenemase gene, with 32 (86%) carrying OXA-48 and 7 (19%) carrying NDM-1. No other carbapenemase genes were identified. All strains carried a CTX-M-2-like beta-lactamase, and some carried SHV- (97%), TEM- (9%), and CTX-M-1-like (62%) beta-lactamases. Sequence analysis of bla(TEM) genes identified a bla(TEM-166) with an amino acid change at position 53 (Arg53Gly) from bla(TEM-1b), the first report of a mutation in this region. REP-PCR analysis revealed that there were seven different clonal groups, and temporo-spatial links were identified within these groups. CONCLUSIONS: Combinations of beta-lactamases were found in all strains, with the most common being OXA-48, SHV, TEM, and CTX-M type (76% of strains). We have reported, for the first time, a high prevalence of the NDM-1 (19%) carbapenemase in carbapenem-resistant K. pneumoniae from Turkey. These enzymes often co-exist with other beta-lactamases, such as TEM, SHV, and CTX-M beta-lactamases. PMID- 26354348 TI - Molecular identification and amphotericin B susceptibility testing of clinical isolates of Aspergillus from 11 hospitals in Korea. AB - BACKGROUND: We investigated the species distribution and amphotericin B (AMB) susceptibility of Korean clinical Aspergillus isolates by using two Etests and the CLSI broth microdilution method. METHODS: A total of 136 Aspergillus isolates obtained from 11 university hospitals were identified by sequencing the internal transcribed spacer (ITS) and beta-tubulin genomic regions. Minimal inhibitory concentrations (MICs) of AMB were determined in Etests using Mueller-Hinton agar (Etest-MH) and RPMI agar (Etest-RPG), and categorical agreement with the CLSI method was assessed by using epidemiological cutoff values. RESULTS: ITS sequencing identified the following six Aspergillus species complexes: Aspergillus fumigatus (42.6% of the isolates), A. niger (23.5%), A. flavus (17.6%), A. terreus (11.0%), A. versicolor (4.4%), and A. ustus (0.7%). Cryptic species identifiable by beta-tubulin sequencing accounted for 25.7% (35/136) of the isolates. Of all 136 isolates, 36 (26.5%) had AMB MICs of >=2 MUg/mL by the CLSI method. The categorical agreement of Etest-RPG with the CLSI method was 98% for the A. fumigatus, A. niger, and A. versicolor complexes, 87% for the A. terreus complex, and 37.5% for the A. flavus complex. That of Etest-MH was <=75% for the A. niger, A. flavus, A. terreus, and A. versicolor complexes but was higher for the A. fumigatus complex (98.3%). CONCLUSIONS: Aspergillus species other than A. fumigatus constitute about 60% of clinical Aspergillus isolates, and reduced AMB susceptibility is common among clinical isolates of Aspergillus in Korea. Molecular identification and AMB susceptibility testing by Etest-RPG may be useful for characterizing Aspergillus isolates of clinical relevance. PMID- 26354349 TI - Increase in anti-Gal IgM level is associated with early graft failure in intraportal porcine islet xenotransplantation. AB - BACKGROUND: Anti-Gal is a major antibody induced in non-human primates (NHPs) after xenotransplantation. To understand the mechanism of graft rejection, we investigated the association between anti-Gal responses and graft failure in NHP recipients of porcine islet transplantation (PITx). METHODS: Intraportal PITx was performed in 35 diabetic NHPs, and graft function was monitored. Early graft failure (EGF) was defined as loss of graft function within a month after PITx. Seven, 19, nine NHPs received immunosuppression (IS) without CD40 pathway blockade (Group I), with anti-CD154 (Group II), and with anti-CD40 (Group III), respectively. The anti-Gal levels on day 0 and day 7 of PITx were measured by ELISA. RESULTS: The frequency of EGF was significantly lower in Group II (26.3%) than in Group I (100%, P=0.0012) and Group III (77.8%, P=0.0166). While levels of anti-Gal IgG in Group I and anti-Gal IgM in Group III increased on day 7 compared with day 0 (P=0.0156 and 0.0273), there was no increase in either on day 7 in Group II. The ratio of anti-Gal IgM or IgG level on day 7 to that on day 0 (Ratio7/0) was significantly higher in recipients with EGF than without EGF (P=0.0009 and 0.0027). ROC curve analysis of anti-Gal IgM Ratio7/0 revealed an area under the curve of 0.789 (P=0.0003). CONCLUSIONS: IS with anti-CD154 suppressed anti-Gal responses and prevented EGF in PITx. Anti-Gal IgM Ratio7/0, being associated with EGF, is a predictive marker for EGF. PMID- 26354350 TI - Duffy blood group genotyping in Thai blood donors. AB - BACKGROUND: Duffy (FY) blood group genotyping is important in transfusion medicine because Duffy alloantibodies are associated with delayed hemolytic transfusion reactions and hemolytic disease of the fetus and newborn. In this study, FY allele frequencies in Thai blood donors were determined by in-house PCR with sequence-specific primers (PCR-SSP), and the probability of obtaining compatible blood for alloimmunized patients was assessed. METHODS: Five hundred blood samples from Thai blood donors of the National Blood Centre, Thai Red Cross Society, were included. Only 200 samples were tested with anti-Fy(a) and anti Fy(b) using the gel technique. All 500 samples and four samples from a Guinea family with the Fy(a-b-) phenotype were genotyped by using PCR-SSP. Additionally, the probability of obtaining antigen-negative red blood cells (RBCs) for alloimmunized patients was calculated according to the estimated FY allele frequencies. RESULTS: The FY phenotyping and genotyping results were in 100% concordance. The allele frequencies of FY*A and FY*B in 500 central Thais were 0.962 (962/1,000) and 0.038 (38/1,000), respectively. Although the Fy(a-b-) phenotype was not observed in this study, FY*B(ES)/FY*B(ES) was identified by PCR SSP in the Guinea family and was confirmed by DNA sequencing. CONCLUSIONS: Our results confirm the high frequency of the FY*A allele in the Thai population, similar to that of Asian populations. At least 500 Thai blood donors are needed to obtain two units of antigen-negative RBCs for the Fy(a-b+) phenotype. PMID- 26354351 TI - Evaluation of the Anyplex BRAF V600E real-time detection assay using dual-priming oligonucleotide technology in fine-needle aspirates of thyroid nodules. AB - BACKGROUND: Several molecular assays have been developed to detect the BRAF V600E mutation in fine needle aspirates (FNAs) for the diagnosis of papillary thyroid cancer. Using a multiplex PCR technique, we evaluated the Anyplex BRAF V600E Real time Detection (Anyplex) assay and compared its efficacy with that of the Seeplex BRAF V600E ACE Detection (Seeplex) method. METHODS: We tested 258 consecutive FNA specimens using the Seeplex and Anyplex assays. Any conflicting results between the two assays were confirmed by using mutant enrichment with 3'-modified oligonucleotide (MEMO) sequencing. The limits of detection (LODs) and reproducibility for each assay were evaluated with serially diluted DNA from a BRAF V600E-positive cell line. RESULTS: The BRAF V600E mutation was detected in 36.4% (94/258) FNA specimens by either the Seeplex or Anyplex assay. Results for the two assays showed 93.4% (241/258) agreement, with a kappa value of 0.861 (95% confidence interval, 0.798-0.923). Of the eight specimens that were BRAF V600E positive by the Anyplex assay but not by the Seeplex assay, five were found to be BRAF V600E-positive by MEMO sequencing. The mutation detection rate of the Seeplex and Anyplex assays was 79.0% and 84.0%, respectively, in the FNA specimens diagnosed as malignant (n=81). The LOD as determined by probit analysis was 0.046% (95% confidence interval, 0.019-0.532%). CONCLUSIONS: The Anyplex assay performed better than the Seeplex assay with respect to the detection of the BRAF V600E mutation. PMID- 26354352 TI - Association between high platelet indices and proteinuria in patients with hypertension. AB - BACKGROUND: We aimed to determine the association between platelet indices including plateletcrit (PCT), mean platelet volume (MPV), platelet distribution width (PDW), and proteinuria associated with hypertension (HT) as well as the relative power of each to predict proteinuria. METHODS: The study included 223 patients (68 men and 155 women) with primary HT. PCT, MPV, PDW, and proteinuria levels were measured. The patients were divided into two groups according to proteinuria status based on 24-hr urinary protein excretion: proteinuria (+) group (15 men and 40 women) and proteinuria (-) group (53 men and 115 women). RESULTS: The mean and SD of platelet count, PDW, PCT, and MPV were 278.8+/ 49.6*108/L, 13.5+/-1.8%, 0.31+/-0.07%, and 11.3+/-2.6 fL, respectively. The mean platelet count, PCT, MPV, and PDW were significantly higher in the proteinuria (+) group than in the proteinuria (-) group (P<0.05); there were no significant differences in the other blood parameters between the two groups. The platelet count, PCT, MPV, and PDW were independent risk factors predictive of proteinuria according to a stepwise regression analysis of PDW, PCT, and MPV. PCT was the strongest independent predictor of proteinuria. CONCLUSIONS: The platelet indices PCT, PDW, and MPV were significantly higher in patients with proteinuria than in those without it. Among these three indices, PCT was the strongest predictor of proteinuria. PMID- 26354353 TI - Establishing quality control ranges for antimicrobial susceptibility testing of Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus: a cornerstone to develop reference strains for Korean clinical microbiology laboratories. AB - Quality control (QC) processes are being performed in the majority of clinical microbiology laboratories to ensure the performance of microbial identification and antimicrobial susceptibility testing by using ATCC strains. To obtain these ATCC strains, some inconveniences are encountered concerning the purchase cost of the strains and the shipping time required. This study was focused on constructing a database of reference strains for QC processes using domestic bacterial strains, concentrating primarily on antimicrobial susceptibility testing. Three strains (Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus) that showed legible results in preliminary testing were selected. The minimal inhibitory concentrations (MICs) and zone diameters (ZDs) of eight antimicrobials for each strain were determined according to the CLSI M23. All resulting MIC and ZD ranges included at least 95% of the data. The ZD QC ranges obtained by using the CLSI method were less than 12 mm, and the MIC QC ranges extended no more than five dilutions. This study is a preliminary attempt to construct a bank of Korean QC strains. With further studies, a positive outcome toward cost and time reduction can be anticipated. PMID- 26354354 TI - Novel pathogenic variant (c.3178G>A) in the SMC1A gene in a family with Cornelia de Lange syndrome identified by exome sequencing. AB - Cornelia de Lange syndrome (CdLS) is a clinically and genetically heterogeneous congenital anomaly. Mutations in the NIPBL gene account for a half of the affected individuals. We describe a family with CdLS carrying a novel pathogenic variant of the SMC1A gene identified by exome sequencing. The proband was a 3-yr old boy presenting with a developmental delay. He had distinctive facial features without major structural anomalies and tested negative for the NIPBL gene. His younger sister, mother, and maternal grandmother presented with mild mental retardation. By exome sequencing of the proband, a novel SMC1A variant, c.3178G>A, was identified, which was expected to cause an amino acid substitution (p.Glu1060Lys) in the highly conserved coiled-coil domain of the SMC1A protein. Sanger sequencing confirmed that the three female relatives with mental retardation also carry this variant. Our results reveal that SMC1A gene defects are associated with milder phenotypes of CdLS. Furthermore, we showed that exome sequencing could be a useful tool to identify pathogenic variants in patients with CdLS. PMID- 26354355 TI - Cryptic e1a2 BCR-ABL1 fusion with complex chromosomal abnormality in de novo myelodysplastic syndrome. PMID- 26354356 TI - Use of delta neutrophil index for differentiating low-grade community-acquired pneumonia from upper respiratory infection. PMID- 26354357 TI - Straightforward identification of masked polycythemia vera based on proposed revision of World Health Organization diagnostic criteria for BCR-ABL1-negative myeloproliferative neoplasms. PMID- 26354358 TI - The first case of concurrent infective endocarditis and spondylitis caused by Streptococcus tigurinus. PMID- 26354359 TI - Campylobacter hyointestinalis isolated from a human stool specimen. PMID- 26354360 TI - Anti-rods and rings autoantibodies in a patient with hepatitis C virus infection. PMID- 26354361 TI - Isochromosome 1q in childhood Burkitt lymphoma: the first reported case in Korea. PMID- 26354362 TI - Erratum. PMID- 26354363 TI - beta-Arrestin1 regulates the morphology and dynamics of microglia in zebrafish in vivo. AB - Microglia are the primary immune cells in the central nervous system. Microglia typically exist in a 'resting' state in the healthy brain, with ramified processes dynamically exploring the surrounding microenvironment. They become 'activated' under pathological conditions with marked changes in morphology. However, the regulation of their morphology dynamics remains poorly understood. Here, using in vivo time-lapse imaging and three-dimensional morphology analysis of microglia in intact zebrafish larvae, we found that beta-arrestin1, a multifunctional protein involved in various signal transductions, cell autonomously regulated the microglial morphology. Knockdown of beta-arrestin1 increased the volume size and process number of microglia but reduced the deformation speed in the resting state. Meanwhile, beta-arrestin1 down-regulation led to a high frequency of phagocytic behaviour of microglia. These defects were partially rescued by over-expressing human beta-arrestin1 in microglia. Our study indicated that microglial dynamics in the resting state can be regulated cell autonomously by beta-arrestin1 signalling. PMID- 26354364 TI - Feasibility of carotid artery stenting with double cerebral embolic protection in high-risk patients. AB - BACKGROUND: Previous trials comparing carotid artery stenting (CAS) with carotid endarterectomy have shown that the former can increase the stroke rate. However, in the last years, because of the improvements either of the technique or the improvement of the stents and embolic protection devices (EPD), CAS has become a very competitive procedure. In this study, we tried to assess the feasibility and the safety of using double EPD (proximal and distal) in high-risk patients. METHODS: We collected data about all consecutive patients with carotid artery stenosis who underwent CAS and compared clinical and procedural characteristics as well as immediate and 30-day outcomes between the use of double vs. single EPD. RESULTS: Between November 2007 and August 2014, 294 patients underwent CAS. In 35 of them (11.9%) double EPD was used. In comparison with the patients treated with single EPD, those with double EPD presented more with acute carotid syndrome (recurrent TIAs < 48 hr, minor stroke < 14 days) and with complex plaque (79.4 vs. 33.6%, P < 0.0001). There was no difference between the 2 groups in primary success (100 vs. 99.6%, P = 0.16) and in 30-days major complications: death (0 vs. 0.8%, P = 0.6), major stroke (0 vs. 0.8%, P = 0.42), and minor stroke (0 vs 1.1%, P = 0.66). CONCLUSIONS: In our experience, in high-risk patients with high-risk lesions, the use of double EPD (proximal and distal) is safe and effective in minimizing the risk of cerebral embolization, but, to validate such a technique in wide range of patients, further studies are warranted. PMID- 26354366 TI - Editorial: Role of Data and Methods in Chemoinformatics for Virtual Screening. PMID- 26354365 TI - Single gene locus changes perturb complex microbial communities as much as apex predator loss. AB - Many bacterial species are highly social, adaptively shaping their local environment through the production of secreted molecules. This can, in turn, alter interaction strengths among species and modify community composition. However, the relative importance of such behaviours in determining the structure of complex communities is unknown. Here we show that single-locus changes affecting biofilm formation phenotypes in Bacillus subtilis modify community structure to the same extent as loss of an apex predator and even to a greater extent than loss of B. subtilis itself. These results, from experimentally manipulated multitrophic microcosm assemblages, demonstrate that bacterial social traits are key modulators of the structure of their communities. Moreover, they show that intraspecific genetic variability can be as important as strong trophic interactions in determining community dynamics. Microevolution may therefore be as important as species extinctions in shaping the response of microbial communities to environmental change. PMID- 26354367 TI - Is the Problem Cultural Incompetence or Racism? AB - Clinical competence-including asking about and understanding the impact of a patient's culture-should be what we all expect when we seek treatment. Behavioral health organizations have opportunities to create culturally competent and responsive services. But we need to add another call to action-acknowledging and addressing the disparities caused by racism. PMID- 26354368 TI - The effects of non-invasive respiratory support on oropharyngeal temperature and humidity: a neonatal manikin study. AB - OBJECTIVE: Heating and humidification of inspired gases is routine during neonatal non-invasive respiratory support. However, little is known about the temperature and humidity delivered to the upper airway. The International Standards Organization (ISO) specifies that for all patients with an artificial airway humidifiers should deliver >=33 g/m(3) absolute humidity (AH). We assessed the oropharyngeal temperature and humidity during different non-invasive support modes in a neonatal manikin study. METHODS: Six different modes of non-invasive respiratory support were applied at clinically relevant settings to a neonatal manikin, placed in a warmed and humidified neonatal incubator. Oropharyngeal temperature and relative humidity (RH) were assessed using a thermohygrometer. AH was subsequently calculated. RESULTS: Measured temperature and RH varied between devices. Bubble and ventilator continuous positive airway pressure (CPAP) produced temperatures >34 degrees C and AH >38 g/m(3). Variable flow CPAP resulted in lower levels of AH than bubble or ventilator CPAP, and AH decreased with higher gas flow. High-flow (HF) therapy delivered by Optiflow Junior produced higher AH with higher gas flow, whereas with Vapotherm HF the converse was true. CONCLUSIONS: Different non-invasive devices deliver inspiratory gases of variable temperature and humidity. Most AH levels were above the ISO recommendation; however, with some HF and variable flow CPAP devices at higher gas flow this was not achieved. Clinicians should be aware of differences in the efficacy of heating and humidification when choosing modes of non-invasive respiratory support. PMID- 26354369 TI - Preterm infant growth and asthma at age 8 years. AB - OBJECTIVES: To examine associations of gain in body mass index (BMI) and linear growth from term to 18 months with asthma at age 8 years in a cohort of preterm infants. We hypothesised that rapid BMI gain would increase asthma risk, whereas rapid linear growth would be protective. DESIGN: Observational secondary analysis of data from the Infant Health and Development Program. SETTING: 8 centres in the USA. PATIENTS: 863 preterm (<=37 weeks), low birthweight (<=2500 g) children. MAIN EXPOSURE VARIABLES: Gain in BMI and linear growth from term to 4 months, 4 12 months and 12-18 months, in z-scores. MAIN OUTCOME MEASURE: Asthma at age 8 years, assessed by parent report of the child ever receiving the diagnosis from a doctor. RESULTS: At age 8 years, 149 (17%) had ever been diagnosed with asthma. Adjusting for maternal and child factors in logistic regression, for each additional z-score gain in BMI from term to 4 months, odds of asthma at age 8 years were higher (OR 1.3, 95% CI 1.1 to 1.5); findings were similar for BMI gain from 4-12 months. More rapid linear growth from term to 4 months was not associated with lower odds of asthma (OR 1.1, 95% CI 0.9 to 1.3), with similar findings for 4-12 months and 12-18 months. CONCLUSIONS: More rapid BMI gain in the 1st year of life was associated with higher odds of asthma, whereas linear growth did not appear protective. Our results add to mounting evidence that excess weight gain after term may be harmful to preterm infants. PMID- 26354370 TI - Characterization of air freshener emission: the potential health effects. AB - Air freshener could be one of the multiple sources that release volatile organic compounds (VOCs) into the indoor environment. The use of these products may be associated with an increase in the measured level of terpene, such as xylene and other volatile air freshener components, including aldehydes, and esters. Air freshener is usually used indoors, and thus some compounds emitted from air freshener may have potentially harmful health impacts, including sensory irritation, respiratory symptoms, and dysfunction of the lungs. The constituents of air fresheners can react with ozone to produce secondary pollutants such as formaldehyde, secondary organic aerosol (SOA), oxidative product, and ultrafine particles. These pollutants then adversely affect human health, in many ways such as damage to the central nervous system, alteration of hormone levels, etc. In particular, the ultrafine particles may induce severe adverse effects on diverse organs, including the pulmonary and cardiovascular systems. Although the indoor use of air freshener is increasing, deleterious effects do not manifest for many years, making it difficult to identify air freshener-associated symptoms. In addition, risk assessment recognizes the association between air fresheners and adverse health effects, but the distinct causal relationship remains unclear. In this review, the emitted components of air freshener, including benzene, phthalate, and limonene, were described. Moreover, we focused on the health effects of these chemicals and secondary pollutants formed by the reaction with ozone. In conclusion, scientific guidelines on emission and exposure as well as risk characterization of air freshener need to be established. PMID- 26354371 TI - Protective effect of N-acetylcysteine against nicardipine hydrochloride-induced autophagic cell death of human vascular endothelial cells. AB - Nicardipine hydrochloride (NIC) injection has been widely used for emergency treatment of abnormally high blood pressure. However, NIC injection often causes severe peripheral vascular injury. The purpose of the present study was to reduce the NIC-induced cell injury in human vascular endothelial cells by use of clinical agents. The mechanism of NIC-induced cell injury was evaluated by time lapse microscopic imaging, autophagosome staining with monodansylcadaverine, immunostaining of light chain 3 isoform B (LC-3B) and assessment of cell viability after exposure to NIC with or without an inhibitor of autophagosome formation (3-methyladenine, 3-MA). Results from autophagosome labeling and immunostaining of LC-3B revealed an increase of autophagosomes and LC-3B in NIC treated cells. NIC-mediated reduction of cell viability was inhibited by 3 methyladenine. Moreover, we found that N-acetylcysteine (NAC) reduced NIC-induced cell injury in human vascular endothelial cells. These findings suggest that NIC causes severe peripheral venous irritation via induction of autophagic cell death and that inhibition of autophagy with NAC could contribute to the reduction of NIC-induced vascular injury. PMID- 26354372 TI - Activation of transcription factors in a mouse lung following exposure to environmental chemical and biological agents. AB - Environmental biological and chemical agents can modulate innate and acquired immunity in the lung via the stimulation of Toll-like receptors (TLRs). To investigate the effect of environmental chemical agents on the activation of NF kappaB and activator protein (AP)-1 subunits and the role of TLR4 signaling in the lung, C3H/HeN and C3H/HeJ (TLR4-defective) mice were exposed to 0 or 50 ppm of toluene for 6 hr/day, 5 days/week for 6 weeks. Some groups of mice were also stimulated with OVA or LPS as a biological agent. The DNA-binding activities of the NF-kappaB subunits (p50, p52, p65 and RelB) and AP-1 family members (FosB, c Fos, +c-Jun, JunD) were compared using TransAM ELISA kits. Exposure to toluene alone produced no significant changes in both mice. Although stimulation with OVA or LPS alone significantly increased the DNA binding activities of p50 and p52 in C3H/HeN mice, there were no interactions between biological factors and toluene. In the C3H/HeJ mice, stimulation with OVA or LPS increased p65 and p52 binding activity and the combination of exposure to toluene and OVA significantly increased the DNA binding activities of the p65 and p52 in the lung. During AP-1 activation, co-exposure to toluene and OVA increased JunD binding activity in C3H/HeJ mice, while co-exposure to toluene and LPS influenced c-Fos binding activity in C3H/HeN mice. These results indicate that TLR4 may play an important role in activation of NF-kappaB or AP-1 family following exposure to environmental biological and chemical agents. PMID- 26354373 TI - Prenatal low-dose bisphenol A enhances behavioral responses induced by a predator odor. AB - Bisphenol A (BPA) is an environmental endocrine disrupter (EED). Previous studies by our group showed that pre- and postnatal administration of low-level BPA induced depression-like behavior in rats. In this study, we evaluated the effects of prenatal BPA on behavioral responses to a predator odor by using a novel cross form apparatus consisting of 4 plastic chambers. On the first day, nothing was placed into the chambers (Session 1). On the second day, a predator odor (fox odor) was located in separate chambers at 2 opposite corners of the apparatus (Session 2). Pregnant Wistar rats were exposed to low-dose BPA (less than the reference dose) during the 7 days just before birth, and the offspring of the treated rats were evaluated as adults. The locomotor activity and avoidance response of each rat on both test days were compared. The control and BPA groups showed reduced locomotor activity in the presence of the predator odor, but the odor-avoidance response was significant only in the BPA rats. The BPA-exposed rats were obviously sensitive to the predator odor. These results suggest that prenatal BPA exposure has an amplifying effect on avoidance responses to predator odor stress. PMID- 26354374 TI - Effects of glutathione on the in vivo metabolism and oxidative stress of arsenic in mice. AB - In this study, we investigated the in vivo effects of exogenous glutathione and buthionine sulfoximine on arsenic methylation and antioxidant capacity in mice exposed to arsenic via drinking water. Thirty-six female albino mice were randomly divided into six groups. All groups were given free access to drinking water that contained arsenic continuously except the control group. After ten days, mice were treated with different levels of glutathione or buthionine sulfoximine. The levels of the metabolites of arsenic were determined in the liver and urine. The levels of glutathione and total antioxidant capacity were determined in the whole blood and liver. Our results showed that the increase of arsenic species in the liver as well as the decrease of blood and hepatic glutathione and total antioxidant capacity, were all relieved by exogenous glutathione consistently. We also observed the involvement of glutathione in promoting arsenic methylation and urinary elimination in vivo. Increase of total arsenic in the urine was mainly due to the increase of dimethylated arsenic. Furthermore, administration of glutathione increased the first methylation ratio and secondary methylation ratio in the liver and urine, which resulted in the consequent increase of dimethylated arsenic percent and decrease of inorganic arsenic percent in the urine. Opposite effects appeared with the administration of buthionine sulfoximine, a scavenger of glutathione. Our study indicated that exogenous glutathione not only accelerated the methylation and the excretion of arsenic, but also relieve the arsenic-induced oxidative stress. This provides a potential useful chemopreventive dietary component for human populations being at risk of arsenic exposure. PMID- 26354375 TI - Adenoviral vector expressing IGF-1 protects murine chondrogenic ATDC5 cells against hydrogen peroxide-induced mitochondrial dysfunction and apoptosis. AB - Insulin-like growth factor-1 (IGF-1), with an age-related decline, regulates the proliferation and survival of multiple cell types, particularly stimulates cartilage matrix synthesis, and inhibits matrix degradation. The present study was to investigate the regulatory role of IGF-1 against hydrogen peroxide(H2O2) induced mitochondrial dysfunction and apoptosis in murine chondrocytic ATDC5 cells. We firstly determined mitochondrial dysfunction and apoptosis in ATDC5 cells which were exposed to H2O2. We then constructed an IGF-1-overexpressed adenovirus (IGF-1-Ad) harboring the IGF-1 coding sequence, and investigated the regulatory role of the overexpressed IGF-1 against the H2O2-induced mitochondrial dysfunction and apoptosis in ATDC5 cells. It was demonstrated that H2O2 treatment promoted the mitochondrial dysfunction, and further reduced the viability and induced apoptosis of ATDC5 cells. However, the IGF-1 overexpression by adenovirus inhibited the H2O2-induced mitochondrial dysfunction and further inhibited the H2O2-promoted apoptosis in ATDC5 cells. In conclusion, the present study found that oxidative stress promoted mitochondrial dysfunction and induced apoptosis in the murine chondrocytic ATDC5 cells, and the adenoviral vector-expressed IGF-1 protected the murine chondrocytic ATDC5 cells against such mitochondrial dysfunction and apoptosis. This study implies the protective role of IGF-1 against the oxidative stress in murine chondrocytic ATDC5 cells and demonstrates the promising anti-oxidative stress effect of the recombinant IGF-1-Ad against oxidative stress in chondrocytic cells. PMID- 26354376 TI - Participation of metabolic activation of 2,4,6-trinitrotoluene to 4-hydroxylamino 2,6-dinitrotoluene in hematotoxicity. AB - Exposure to 2,4,6-trinitrotoluene (TNT) causes methemoglobin (metHb) formation, hemolysis and negative heme balance in vivo, but the mechanistic details are poorly understood. In the present study, we examined the participation of metabolic activation in TNT-mediated hematotoxicity. Exposure of rats with TNT (300 mg/kg, i.p.) for 4 days resulted in a decrease of hematocrit value coupled to an increase in metHb formation. The red blood cells treated with 4 hydroxylamino-2,6-dinitrotoluene (HADNT), a metabolite of TNT, underwent readily hemolysis in vitro, whereas such a phenomenon was not seen with TNT. Consistent with this, HADNT is active toward metHb formation and the decrease in thiol content of the globin moiety compared with TNT and its metabolites 4-amino-2,6 dinitrotoluene (ADNT) and 4-acetylamino-2,6-dinitrotoluene (AADNT). Furthermore, interaction of purified rat oxyhemoglobin (oxyHb) with HADNT, but not TNT, ADNT, and AADNT, caused a concentration-dependent production of H2O2 and ferrylhemoglobin (ferrylHb) which is a highly oxidizing state formed by reaction of oxyHb with H2O2. Notably, hemin was released during interaction of oxyHb with HADNT. Taken together, these findings suggest that HADNT is an active metabolite that mediates TNT-induced hematotoxicity via formation of prooxidants such as H2O2 and ferrylHb. PMID- 26354377 TI - Endothelial dysfunction in subjects with chronic cadmium exposure. AB - Vascular endothelium is a target of cadmium (Cd) toxicity. Cd exposure has been reported to be associated with vascular disorders. In this study, we aimed to investigate the effects of Cd exposure on markers of endothelial function in human subjects chronically exposed to Cd. Based on blood Cd levels, seventy-five women were categorized into non-exposed, Cd-exposed and severely Cd-exposed groups. Nitrite, L-arginine, asymmetric dimethylarginine (ADMA), and soluble thrombomodulin levels in blood were measured. Nitrite levels were lower in Cd exposed subjects than non-exposed subjects. Plasma L-arginine decreased while ADMA, an endogenous endothelial nitric oxide synthase (eNOS) inhibitor, increased in Cd-exposed subjects. Soluble thrombomodulin also increased in Cd-exposed subjects. In Cd-exposed subjects, plasma malondialdehyde and protein carbonyl groups increased while the erythrocytic glutathione decreased. Multiple linear regression analysis revealed a negative association between urinary Cd and nitrite levels in erythrocytes. Our research suggests that subjects with chronic Cd exposure have endothelial dysfunction. PMID- 26354378 TI - Sirt 1 activator inhibits the AGE-induced apoptosis and p53 acetylation in human vascular endothelial cells. AB - Advanced glycation end products (AGEs) by nonenzymatic glycation reactions are extremely accumulated in the diabetic vascular cells, neurons, and glia, and are confirmed to play important role in the pathogenesis of diabetes mellitus induced cardiovascular complications. Sirt 1, known as mammalian sirtuin, has been recognized to regulate insulin secretion and protect cells against oxidative stress, which is promoted by the accumulated AGEs in cardiovascular cells. In the present study, we treated human endothelial Eahy926 cells with AGEs, and determined the apoptosis induction, caspase activation, the Sirt 1 activity, the expression and acetylation of p53. Then we manipulated Sirt 1 activity with a Sirt 1 activator, Resveratrol (RSV), and a Sirt 1 inhibitor, sirtinol, in the AGE BSA-treated Eahy926 cells, and then re-evaluated the apoptosis induction, caspase activation, the expression and acetylation of p53. Results demonstrated that AGEs induced apoptosis in the human endothelial Eahy926 cells, by promoting the cytochrome c release, activation of caspase 9/3. Also, the AGE-BSA treatment promoted the total p53 level and acetylated (Ac) p53, but reduced the Sirt 1 level and activity. On the other hand, the Sirt 1 inhibitor/activator not only deteriorated/ameliorated the promotion to p53 level and Ac p53, but also aggravated/inhibited the AGE-induced apoptosis and the promotion to apoptosis associated signaling molecules. In conclusion, the present study confirmed the apoptosis promotion by AGEs in endothelial Eahy926 cells, by regulating the Sirt 1 activity and p53 signaling, it also implies the protective role of Sirt 1 activator against the AGE-induced apoptosis. PMID- 26354379 TI - Calcium ions rescue human lung epithelial cells from the toxicity of zinc oxide nanoparticles. AB - Contradictory results have been reported for in vitro evaluations of whether zinc oxide nanoparticles (ZnO NPs) are cytotoxic. Though there have been reports of ZnO NPs cytotoxicity due to Zn ions released from the nanoparticles, there have also been reports concluding that Zn ions are not cytotoxic. This inconsistency is mostly attributed to the types of cells used. In this research, we investigated the difference in the level of ZnO NPs cytotoxicity due to culturing conditions. The sensitivity of human lung epithelial cells to ZnO NPs cytotoxicity differed depending on the dispersing medium, physiological state of the cells resulting from their growth stage, and composition of the medium. Further, with regard to the toxicity of ZnO NPs, NPs internalized into cells had a greater cytotoxic effect than Zn ions released from ZnO NPs. Instead of inducing cell death, ZnO NPs internalized into cells slowed the rate of cell proliferation. Furthermore, the cytotoxicity of ZnO NPs depended greatly on the concentration of calcium ions (Ca2+) in the medium. When the concentration of Ca2+ was low, the cytotoxicity of ZnO NPs increased markedly. However, the toxicity of ZnO NPs was mitigated by the addition of CaCl2 to the medium. Global gene expression analysis revealed that Ca2+ -induced upregulation of cell cycle functions could be attributable to the mitigation of ZnO NP toxicity by Ca2+. PMID- 26354380 TI - FOXO1 silence aggravates oxidative stress-promoted apoptosis in cardiomyocytes by reducing autophagy. AB - Mechanisms underlining oxidative stress-induced injury to cardiomyocytes during myocardial infarction (MI) or acute ischemia/reperfusion (I/R) are not well recognized. Forkhead box O (FOXO) transcription factors have been defined as critical mediators of oxidative stress resistance in multiple cell types, but their cardioprotective functions have not been reported previously. In the present study, we investigated the promotion to FOXO1 by the treatment with hydrogen peroxide (H2O2) during the H2O2-induced apoptosis in cardiomyocyte H9c2 cells. We then silenced FOXO1 with FOXO1-specific siRNA, and re-evaluated the H2O2-induced apoptosis. In addition, we also examined the H2O2-induced autophagy and the autophagy induction post FOXO1 silence. Results demonstrated that H2O2 induced a significantly high level of apoptosis in H9c2 cells. Interestingly, the FOXO1 in both mRNA and protein levels were not significantly regulated, however, the phosphorylated form of FOXO1 was significantly promoted in the H2O2-treated H9c2 cells. On the other hand, post the significant knockout of FOXO1 with the transfection with FOXO1-specific siRNA, the apoptosis induction was more significant in H9c2 cells subjected to H2O2. In addition, we found a significantly higher level of autophagy induction in the H2O2-treated H9c2 cells. However, the autophagy was markedly reduced by the knockout of FOXO1. In summary, these data support the critical role for FOXO1 in promoting cardiomyocytes against oxidative stress probably through inducing autophagy. PMID- 26354381 TI - Modifying effects of 1,2-dichloropropane on N-nitrosobis(2-oxopropyl)amine induced cholangiocarcinogenesis in male Syrian hamsters. AB - Based on the findings of epidemiological studies in Japan that occupational exposure to 1,2-dichloropropane (1,2-DCP) was associated with increased cholangiocarcinomas, 1,2-DCP has recently been classified as being carcinogenic to humans (Group 1). However, the cholangiocarcinogenicity of 1,2-DCP has not been demonstrated experimentally, and it was negative for cholangiocarcinogenicity in rats and mice. The present study determined the effects of 1,2-DCP on N-nitrosobis(2-oxopropyl)amine (BOP)-induced cholangiocarcinogenesis in male hamsters. We found that 1,2-DCP did not enhance the development of BOP-induced atypical biliary hyperplasia and did not induce any lesions in liver bile duct when administered alone. Notably, 1,2-DCP had no effect on the proliferative activity of bile duct epithelial cells regardless of BOP-initiation. These results demonstrate that 1,2-DCP lacks promoting effects on BOP-induced cholangiocarcinogenesis and suggest the possibility that 1,2-DCP is not cholangiocarcinogenic to the hamster in the present model. In addition, 1,2 DCP also lacks promoting effects on pancreatic, lung, and renal carcinogenesis. As the occurrence of occupational cholangiocarcinomas in Japan might be attributed to exposure to multiple chemicals, the results of the present study indicate that it will be necessary to determine the cholangiocarcinogenic effects of concurrent exposure of 1,2-DCP and the other halogen solvents to which workers with cholangiocarcinomas were exposed. PMID- 26354382 TI - Ochratoxin A induces DNA damage and G2 phase arrest in human esophageal epithelium Het-1A cells in vitro. AB - Ochratoxin A (OTA), a toxin produced by several species of Aspergillus and Penicillium, is one of the most abundant food-contaminating mycotoxins. The International Agency for Research on Cancer (IARC) has classified OTA as a possible human carcinogen. Our previous study showed that there were high levels of OTA contaminations in wheat in the areas with high incidence of esophageal cancer in north China. This finding suggests that exposure to low levels of OTA may be a critical etiological factor for esophageal cancer in these areas. However, up to now, the potential biological effects of OTA on human esophageal epithelial cells have not been fully elucidated. In the present study, we explored the cytotoxicity of OTA in human esophageal epithelium immortalized cells (Het-1A). We found that OTA could induce DNA strand breaks and chromosome aberrations in Het-1A cells. OTA-induced DNA damage was followed by G2 cell cycle arrest, and down-regulation of Cdc2 and cyclinB1 contributed to the OTA-induced G2 arrest in Het-1A cells. Additionally, OTA induced apoptosis in Het-1A cells by activating caspase-3. In conclusion, our results indicated that OTA could induce DNA damage, G2 arrest and apoptosis in Het-1A cells, which may be involved in the esophageal toxicity of OTA. PMID- 26354383 TI - Mixed meal ingestion diminishes glucose excursion in comparison with glucose ingestion via several adaptive mechanisms in people with and without type 2 diabetes. AB - AIMS: To study the integrative impact of macronutrients on postprandial glycaemia, beta-cell function, glucagon and incretin hormones in humans. METHODS: Macronutrients were ingested alone (glucose 330 kcal, protein 110 kcal or fat 110 kcal) or together (550 kcal) by healthy subjects (n = 18) and by subjects with drug-naive type 2 diabetes (T2D; n = 18). beta-cell function and insulin clearance were estimated by modelling glucose, insulin and C-peptide data. Secretion of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) were measured, and paracetamol was administered to estimate gastric emptying. RESULTS: In both groups, the mixed-meal challenge diminished glucose excursion compared with glucose challenge alone, and insulin levels, but not C-peptide levels, rose more than after the mixed meal than after glucose alone. beta-cell function was augmented, insulin clearance was reduced and glucagon levels were higher after the mixed meal compared with glucose alone. GLP 1 and GIP levels increased after all challenges and GIP secretion was markedly higher after the mixed meal than after glucose alone. The appearance of paracetamol was delayed after the mixed-meal challenge compared with glucose alone. CONCLUSIONS: Adding protein and fat macronutrients to glucose in a mixed meal diminished glucose excursion. This occurred in association with increased beta-cell function, reduced insulin clearance, delayed gastric emptying and augmented glucagon and GIP secretion. This suggests that the macronutrient composition regulates glycaemia through both islet and extra-islet mechanisms in both healthy subjects and in subjects with T2D. PMID- 26354384 TI - A Central Incisor with 4 Independent Root Canals: A Case Report. AB - The maxillary central incisor is the tooth with the least anatomic variations. Despite the fact that several studies have reported a prevalence of 100% for the presence of a single canal, root canal aberrations of maxillary central incisors with up to 3 canals have also been reported. Such cases represent both a diagnostic and technical challenge to the clinician. The present case describes root canal treatment performed in a maxillary central incisor with 4 canals. The detection of all canals was achieved by examination of the pulp chamber floor with the help of the dental operating microscope as well as careful examination of intraoral radiographs. The canals were prepared with hand and rotary instruments and obturated with a warm gutta-percha technique. The present report is the first to describe a maxillary central incisor with 4 canals in a tooth with no developmental abnormalities. It stresses the importance of using a dental operating microscope during endodontic treatment as well as questioning the routine use of cone-beam computed tomographic imaging for similar cases. PMID- 26354386 TI - Pseudoachalasia secondary to bariatric surgery. AB - Secondary achalasia may result from diseases that either infiltrate or compress the lower esophageal sphincter to create an increased high-pressure zone and subsequent esophageal body changes. With bariatric surgery, a potential high pressure zone is created by a sleeve, band, or bypass just distal to the esophagus. We report four patients who years after a bariatric procedure developed dysphagia followed by esophageal body radiographic and/or manometric features of achalasia. In addition, each of these patients responded symptomatically to endoscopic or surgical therapy either which lowered this high pressure zone. Furthermore, review of prior cases in the literature suggests this has occurred before. Physicians should be aware of this association but further study is needed on its true prevalence. PMID- 26354385 TI - Community Physician-Guided Long-Term Domiciliary Oxygen Therapy Combined With Conventional Therapy in Stage IV COPD Patients. AB - PURPOSE: The aim of the study was to explore clinical effect of community physician-guided long-term domiciliary oxygen therapy (LTDOT) on patients with Stage IV chronic obstructive pulmonary disease (COPD). DESIGN: A retrospective study. METHODS: Fifty-four patients with Stage IV COPD were recruited and randomly divided into two groups (the LTDOT group and the control group). Patients in LTDOT group accepted additional oxygen therapy for more than 15 hours every day with continuous low flow (1-2 L/min) for 3 years. FINDINGS: PaO2 (O2 pressure), FEV1/FVC (forced vital capacity), and FEV1% (percentage of forced expiratory volume in 1 second) in the LTDOT group increased significantly after treatment. A significant decrease was observed on the BODE index in the LTDOT group (p < .05) but not in control group (p > .05). Frequencies and costs of hospitalization therapy and emergency medical services were markedly decreased after 3 years of LTDOT. CONCLUSION: Community physician-guided LTDOT can improve prognosis and reduce the costs for stage IV COPD patients. CLINICAL RELEVANCE: Rehabilitation nurses can be instrumental in helping patients with stage IV COPD learn principles of LTDOT. PMID- 26354387 TI - Control of optical spin Hall shift in phase-discontinuity metasurface by weak value measurement post-selection. AB - Spin Hall effect of light is a spin-dependent transverse shift of optical beam propagating along a curved trajectory, where the refractive index gradient plays a role of the electric field in spin Hall effect of solid-state systems. In order to observe optical spin Hall shift in a refraction taking place at air-glass interface, an amplification technique was necessary such as quantum weak measurement. In phase-discontinuity metasurface (PMS) a rapid phase-change along metasurface takes place over subwavelength distance, which leads to a large refractive index gradient for refraction beam enabling a direct detection of optical spin Hall shift without amplification. Here, we identify that the relative optical spin Hall shift depends on incidence angle at PMS, and demonstrate a control of optical spin Hall shift by constructing weak value measurement with a variable phase retardance in the post-selection. Capability of optical spin Hall shift control permits a tunable precision metrology applicable to nanoscale photonics such as angular momentum transfer and sensing. PMID- 26354388 TI - Development of a model for integrated care at the end of life in advanced dementia: A whole systems UK-wide approach. AB - BACKGROUND: The prevalence of dementia is rising worldwide and many people will die with the disease. Symptoms towards the end of life may be inadequately managed and informal and professional carers poorly supported. There are few evidence-based interventions to improve end-of-life care in advanced dementia. AIM: To develop an integrated, whole systems, evidence-based intervention that is pragmatic and feasible to improve end-of-life care for people with advanced dementia and support those close to them. DESIGN: A realist-based approach in which qualitative and quantitative data assisted the development of statements. These were incorporated into the RAND/UCLA appropriateness method to achieve consensus on intervention components. Components were mapped to underlying theory of whole systems change and the intervention described in a detailed manual. SETTING/PARTICIPANTS: Data were collected from people with dementia, carers and health and social care professionals in England, from expert opinion and existing literature. Professional stakeholders in all four countries of the United Kingdom contributed to the RAND/UCLA appropriateness method process. RESULTS: A total of 29 statements were agreed and mapped to individual, group, organisational and economic/political levels of healthcare systems. The resulting main intervention components are as follows: (1) influencing local service organisation through facilitation of integrated multi-disciplinary care, (2) providing training and support for formal and informal carers and (3) influencing local healthcare commissioning and priorities of service providers. CONCLUSION: Use of in-depth data, consensus methods and theoretical understanding of the intervention components produced an evidence-based intervention for further testing in end-of life care in advanced dementia. PMID- 26354390 TI - Community empowerment: Holistic approach for sustainable improvements in population health. PMID- 26354392 TI - Undoing ignorance: Reflections on strengthening public health institutions in India. PMID- 26354389 TI - Informed consent in paediatric critical care research--a South African perspective. AB - BACKGROUND: Medical care of critically ill and injured infants and children globally should be based on best research evidence to ensure safe, efficacious treatment. In South Africa and other low and middle-income countries, research is needed to optimise care and ensure rational, equitable allocation of scare paediatric critical care resources. Ethical oversight is essential for safe, appropriate research conduct. Informed consent by the parent or legal guardian is usually required for child research participation, but obtaining consent may be challenging in paediatric critical care research. Local regulations may also impede important research if overly restrictive. By narratively synthesising and contextualising the results of a comprehensive literature review, this paper describes ethical principles and regulations; potential barriers to obtaining prospective informed consent; and consent options in the context of paediatric critical care research in South Africa. DISCUSSION: Voluntary prospective informed consent from a parent or legal guardian is a statutory requirement for child research participation in South Africa. However, parents of critically ill or injured children might be incapable of or unwilling to provide the level of consent required to uphold the ethical principle of autonomy. In emergency care research it may not be practical to obtain consent when urgent action is required. Therapeutic misconceptions and sociocultural and language issues are also barriers to obtaining valid consent. Alternative consent options for paediatric critical care research include a waiver or deferred consent for minimal risk and/or emergency research, whilst prospective informed consent is appropriate for randomised trials of novel therapies or devices. We propose that parents or legal guardians of critically ill or injured children should only be approached to consent for their child's participation in clinical research when it is ethically justifiable and in the best interests of both child participant and parent. Where appropriate, alternatives to prospective informed consent should be considered to ensure that important paediatric critical care research can be undertaken in South Africa, whilst being cognisant of research risk. This document could provide a basis for debate on consent options in paediatric critical care research and contribute to efforts to advocate for South African law reform. PMID- 26354391 TI - Enabling public health education reforms in India. PMID- 26354393 TI - Landscaping academic programs offered in demography and population studies in India. AB - As per the United Nations 2013 report, India's population is expected to reach 1.2 billion by 2015. Thus, there is a need for professionals trained in demography and population studies to carry out research regarding population aspects and project population growth/trends. This study landscapes the academic courses being offered in demography and population studies in India (in regular and distance learning modes). It outlines the details of these courses with respect to available courses, fee structure, number of seats, eligibility criteria, duration, nature of the program, etc. The details of the institutes offering demography and population studies courses were collected and compiled. A systematic and predefined approach including Internet search, search in the leading newspapers and discussions with students, academicians, and faculties were used to collect information for different courses provided by institutes all over India. There are around 22 institutions currently offering certificate, diploma, Masters, Master of Philosophy (M.Phil), and doctoral courses in demography and population studies in India (through regular and distance learning modes). Based on the annual intake capacity of these academic institutions, around 1,052 qualified professionals are available to work in the field of demography and population studies in India. This work has helped us to identify and track various academic courses being offered in demography and population studies in India. However, the courses that are being offered are relatively small in number when compared with the number of demographers/population scientists required. A need was also felt to include demography at the Bachelor's degree level. PMID- 26354394 TI - Strategies for attraction and retention of health workers in remote and difficult to-access areas of Chhattisgarh, India: Do they work? AB - BACKGROUND: To address the acute shortages of health workers in underserved, remote, and difficult-to-access areas, the Government of Chhattisgarh and the National Rural Health Mission (NRHM) launched the Chhattisgarh Rural Medical Corps (CRMC) in 2009. CRMC has enabled provisions such as financial incentives, residential accommodation, life insurance, and extra marks during admission at the postgraduate (PG) level to eligible doctors for the attraction and retention of health workers, i.e., doctors, staff nurses, auxiliary nurse midwives (ANMs), and rural medical assistants (RMAs) in underserved areas. OBJECTIVES: This study aims to understand the CRMC scheme in terms of implementation, challenges, gaps, and outcome in achieving the attraction and retention of health workers in the remote and difficult-to-access areas of Chhattisgarh. MATERIALS AND METHODS: The study adopts a mix of both qualitative and quantitative research methods. The purposive sampling method was used for the selection of three districts having normal, difficult, and inaccessible areas. Data were collected through key informant (KI) interviews with beneficiaries and non-beneficiaries of CRMC or district and state government officials, and reviews of document were analyzed using a thematic analysis approach. RESULTS: CRMC has made positive outcome as 1319 health workers, including doctors, have joined the service in 2010-11, reducing the vacancy of doctors from 90% to 45%. The scope of CRMC was primarily limited to payment of monthly financial incentives. The fund utilization rate of CRMC has increased (from 27% in 2009-10 to 98% in 2011-12), though there are delays in payment of incentives. The majority of staff lack awareness about CRMC during job applications. The payment of incentives based on facility performance has demotivated staff. CONCLUSIONS: Establishment of a performance management system, activating the CRMC cell to make it functional, and wide publicity of CRMC benefits are likely to improve attraction and retention of staff. PMID- 26354395 TI - Spiritual health of students in government medical colleges of Kolkata and their coping skills in a crisis situation. AB - BACKGROUND: The status of spiritual health of the population of India at large including that of young medical undergraduates who are the caregivers of the future and its association, if any, with coping skills in crisis situations is yet to be explored. OBJECTIVES: To measure the spiritual health status of the study population, describe the coping skills used by them in crisis situations, identify the sociodemographic factors associated with their spiritual health, and to determine the association of spiritual health status of the study population and their coping skills. MATERIALS AND METHODS: An institution-based cross sectional study was performed among the third semester medical students in government medical colleges of Kolkata, West Bengal, India. The study was conducted among 362 medical students by the survey questionnaire method. The Spiritual Health Scale 2011 (SHS 2011) and the Brief COPE Scale were used to measure the spiritual health and coping status, respectively. RESULTS: Of all the respondents, 75.7% had refined spiritual health. The mean spiritual health score of the female students was significantly higher than that of the males. Of all the students, 66.1% showed good coping scores. Of all the respondents, 86.2% and 24.5% had higher adaptive and maladaptive coping scores, respectively. Refined spiritual categories were seen more among those students whose fathers had higher education and whose families arranged rituals at their homes. The spiritual health, self-evolution, and self-actualization scores of the respondents were significantly related to the adaptive coping scores and the fathers' education. CONCLUSION: The coping skills and hence, the spiritual health of the medical students were greatly influenced by the education of the father and cultural factor(s) like arranging annual rituals at home. PMID- 26354396 TI - A reliable and accurate portable device for rapid quantitative estimation of iodine content in different types of edible salt. AB - BACKGROUND: Continuous monitoring of salt iodization to ensure the success of the Universal Salt Iodization (USI) program can be significantly strengthened by the use of a simple, safe, and rapid method of salt iodine estimation. This study assessed the validity of a new portable device, iCheck Iodine developed by the BioAnalyt GmbH to estimate the iodine content in salt. MATERIALS AND METHODS: Validation of the device was conducted in the laboratory of the South Asia regional office of the International Council for Control of Iodine Deficiency Disorders (ICCIDD). The validity of the device was assessed using device specific indicators, comparison of iCheck Iodine device with the iodometric titration, and comparison between iodine estimation using 1 g and 10 g salt by iCheck Iodine using 116 salt samples procured from various small-, medium-, and large-scale salt processors across India. RESULTS: The intra- and interassay imprecision for 10 parts per million (ppm), 30 ppm, and 50 ppm concentrations of iodized salt were 2.8%, 6.1%, and 3.1%, and 2.4%, 2.2%, and 2.1%, respectively. Interoperator imprecision was 6.2%, 6.3%, and 4.6% for the salt with iodine concentrations of 10 ppm, 30 ppm, and 50 ppm respectively. The correlation coefficient between measurements by the two methods was 0.934 and the correlation coefficient between measurements using 1 g of iodized salt and 10 g of iodized salt by the iCheck Iodine device was 0.983. CONCLUSIONS: The iCheck Iodine device is reliable and provides a valid method for the quantitative estimation of the iodine content of iodized salt fortified with potassium iodate in the field setting and in different types of salt. PMID- 26354397 TI - Growing quackery in dentistry: An indian perspective. AB - Dental disease restricts activities in school, work, and home and often significantly diminishes the quality of life for many children and adults, especially those who have low income or are uninsured. Though the overall dentist population ratio in India is 1:10,000, at present in rural India, one dentist is serving 2.5 lakhs of people. Only 15-20% of people in India are able to get dental services through national schemes, and 80-85% are spending money from their pockets, providing an ideal breeding ground for quackery into dental practice in India. Dental quacks cater to the lower-middle and lower socioeconomic classes that cannot afford qualified dental practitioners. A large number of people visiting these quacks seek care only when in pain, have a restricted budget, and are not very quality conscious. Dentistry has come a long way in the last one and a half century; today it is ranked as one of the most respected professions. It is incumbent upon dentists everywhere to protect this hard-earned reputation by weeding out quacks from among them. The government should urge fresh graduates to practice in rural areas and provide more incentives to them. Public health dentists should take the initiative of adopting more community-oriented oral health programs to increase the awareness among rural populations. PMID- 26354398 TI - Tuberculin skin testing: Spectrum of adverse reactions. AB - Tuberculin skin testing (TST) is one of the primary diagnostic modalities recommended by the World Health Organization (WHO) and the National Institute for Health and Care Excellence (NICE) study conducted in the United Kingdom (UK) for diagnosing tuberculosis (TB). Even after acceptance as a diagnostic modality and stern standardization, TST has its own flaws that include a spectrum of adverse reactions. We report a series of cases with a spectrum of adverse reactions occurring with a higher frequency than present in the available evidence. The study has some demerits such as being a retrospective one with interobserver variation and lack of histopathological confirmation. The observation is presented to accentuate the fact that adverse reactions are not a rarity and that further studies are required to establish the cause and exact incidence of the same. PMID- 26354399 TI - Wealth index and maternal health care: Revisiting NFHS-3. AB - The third National Family Health Survey (NFHS-3) is a large dataset on indicators of family welfare, maternal and child health, and nutrition in India. This article using NFHS-3 data is an attempt to bring out the impact of economic status, i.e., the wealth index on maternal health. The study was based on an analysis of the NFHS-3 data. Independent variables taken were the wealth index, literacy, and age at first child birth. Effects of these variables on the maternal health care services were investigated. Out of the total 124,385 women aged 15-49 years included in the NFHS-3 dataset, 36,850 (29.6%) had one or more childbirth during the past 5 years. The number of antenatal care (ANC) visits increased as the wealth index increased and there was a pattern for choice of place of delivery (for all deliveries during the last 5 years) according to the wealth index. Logistic regression analysis of the abovementioned variables were sought to find out the independent role of key determinants of the different aspects of maternal health care. It showed that the wealth index is the leading key independent determinant for three or more ANC received: Tetanus toxoid (TT) received before delivery, iron tablet/syrup taken for more than 100 days, and institutional delivery. Mother's literacy was the leading independent key determinant for early antenatal registration. The study suggested that along with the mother's literacy, the wealth index that is an important predictor of maternal health care can be added for categorization of the districts for providing differential approach for maternal health care services. PMID- 26354400 TI - Interpersonal communication and contraception: Insights and evidences from Bangladesh demographic and health survey, 2011. AB - This paper examines the role of exposure to mass media and interpersonal communication in predicting the current use of contraception in Bangladesh. Bivariate and multivariate analyses were carried out using the Bangladesh Demographic and Health Survey (BDHS), 2011 data to explore the association between communication and the current use of contraception. After adjusting the related socioeconomic and demographic factors, the mass media did not seem to have any role in predicting contraceptive use behavior while the findings revealed that interpersonal communication [prevalence ratio (PR): 1.0984, 95% confidence interval (CI) 1.0801-1.1170] is a strong positive predictor of the current contraceptive use. It is a well-known fact that mass media performs only the knowledge function while interpersonal communication performs an additional function of persuasion. This analysis corroborates the statement that the role of interpersonal communication is quite important in predicting contraceptive use. PMID- 26354401 TI - Pediatricians' perspectives on pneumococcal conjugate vaccines: An exploratory study in the private sector. AB - There is a lack of information on supply-side determinants, their utilization, and the access to pneumococcal vaccination in India. The objective of this exploratory study was to document the perceptions and perspectives of practicing pediatricians with regard to pneumococcal conjugate vaccines (PCVs) in selected metropolitan areas of India. A qualitative study was conducted to generate evidence on the perspective of pediatricians practicing in the private sector regarding pneumococcal vaccination. The pediatricians were identified from 11 metropolitan areas on the basis of PCV vaccine sales in India through multilevel stratified sampling method. Relevant information was collected through in-depth personal interviews. Finally, qualitative data analysis was carried out through standard techniques such as the identification of key domains, words, phrases, and concepts from the respondents. We observed that the majority (67.7%) of the pediatricians recommended pneumococcal vaccination to their clients, whereas 32.2% recommended it to only those who could afford it. More than half (62.9%) of the pediatricians had no preference for any brand and recommended both a 10 valent pneumococcal conjugate vaccine (PCV10) and a 13-valent PCV (PCV13), whereas 8.0% recommended none. An overwhelming majority (97.3%) of the pediatricians reported that the main reason for a patient not following the pediatrician's advice for pneumococcal vaccination was the price of PCV. To reduce childhood pneumonia-related burden and mortality, pediatricians should use every opportunity to increase awareness about vaccine-preventable diseases, especially vaccine-preventable childhood pneumonia among their patients. PMID- 26354402 TI - Reporting error in the use of multivariable logistic regression. PMID- 26354403 TI - Target intervention to increase measles vaccination coverage by identifying low coverage areas using lot quality assurance sampling, Chennai, India, 2012. PMID- 26354405 TI - Newer innovations in family planning service delivery: A comment on the mobile family planning units. PMID- 26354404 TI - Concept of composite health status index. PMID- 26354406 TI - Public health beyond the millennium development goals. PMID- 26354407 TI - Adsorption of Uranyl ions on Amine-functionalization of MIL-101(Cr) Nanoparticles by a Facile Coordination-based Post-synthetic strategy and X-ray Absorption Spectroscopy Studies. AB - By a facile coordination-based post-synthetic strategy, the high surface area MIL 101(Cr) nanoparticles was functionallized by grafting amine group of ethylenediamine (ED) on coordinatively unsaturated Cr(III) centers, yielding a series of ED-MIL-101(Cr)-based adsorbents and their application for adsorption of U(VI) from aqueous solution were also studied. The obtained ED-functionallized samples with different ED contents were characterized by powder X-ray diffraction (PXRD), scanning electron microscope (SEM), energy dispersive X-ray spectroscopy (EDX), FTIR, elemental analysis (EA) and N2 adsorption and desorption isothermal. Compared with the pristine MIL-101(Cr) sorbents, the ED-functionallized MIL 101(Cr) exhibits significantly higher adsorption capacity for U(VI) ions from water with maximum adsorption capacities as high as 200 mg/g (corresponding to 100% extraction rate) at pH of 4.5 with ED/Cr ratio of 0.68 and the sorbed U(VI) ions can easily be desorbed at lower pH (pH <= 2.0). The adsorption mode of U(VI) ions and effects of grafted ED on the MIL-101(Cr) frameworks were also been studied by X-ray absorption spectroscopy (XAS). We believe that this work establishes a simple and energy efficient route to a novel type of functional materials for U(VI) ions extraction from solution via the post-synthetic modification (PSM) strategy. PMID- 26354408 TI - JTT-553, a novel Acyl CoA:diacylglycerol acyltransferase (DGAT) 1 inhibitor, improves glucose metabolism in diet-induced obesity and genetic T2DM mice. AB - Type 2 diabetes mellitus (T2DM) arises primarily due to lifestyle factors and genetics. A number of lifestyle factors are known to be important in the development of T2DM, including obesity. JTT-553, a novel Acyl CoA:diacylglycerol acyltransferase 1 inhibitor, reduced body weight depending on dietary fat in diet induced obesity (DIO) rats in our previous study. Here, the effect of JTT-553 on glucose metabolism was evaluated using body weight reduction in T2DM mice. JTT 553 was repeatedly administered to DIO and KK-A(y) mice. JTT-553 reduced body weight gain and fat weight in both mouse models. In DIO mice, JTT-553 decreased insulin, non-esterified fatty acid (NEFA), total cholesterol (TC), and liver triglyceride (TG) plasma concentrations in non-fasting conditions. JTT-553 also improved insulin-dependent glucose uptake in adipose tissues and glucose intolerance in DIO mice. In KK-A(y) mice, JTT-553 decreased glucose, NEFA, TC and liver TG plasma concentrations in non-fasting conditions. JTT-553 also decreased glucose, insulin, and TC plasma concentrations in fasting conditions. In addition, JTT-553 decreased TNF-alpha mRNA levels and increased GLUT4 mRNA levels in adipose tissues in KK-A(y) mice. These results suggest that JTT-553 improves insulin resistance in adipose tissues and systemic glucose metabolism through reductions in body weight. PMID- 26354409 TI - Survey on management strategies of rheumatoid arthritis in Saudi Arabia: a Saudi Society for Rheumatology Initiative. AB - AIM: Currently there are no national recommendation guidelines for the management of rheumatoid arthritis (RA) in Saudi Arabia, which has led to a lack of standard of care. The aim of this study is to explore RA management strategies in practicing rheumatologists in Saudi Arabia. METHODS: A 38 questions survey was designed using an electronic website. The survey was distributed through the official email of the Saudi Society for Rheumatology. Rheumatologists with at least 1 year of experience were included. Descriptive analysis was used to report demographics and participants' answers. Chi-square and Fischer's exact test were used to evaluate the relation between the characteristics of participants and their answers. RESULTS: Out of 120 registered practicing adult rheumatologists, 54 (45%) completed the survey. The majority were male 31 (57.4%) and Saudis 36 (66.7%). Forty-two participants (77.8%) use clinical outcome measures in daily clinical practice to guide treatment decisions with the majority using the Disease Activity Score of 28 joints (61.1%). Quality of life measures were used by 22 (40.7%) participants with statistically significant male predominance (P = 0.043). Time consumption was the most important cause for not using any outcome measures. Thirteen (24.1%) and 17 (31.5%) participants do not use parenteral methotrexate and leflunomide, respectively, because of unavailability in the hospital formulary. Nine (16.7%) and 38 (70.37%) participants do not see a role for tofacitinib and biosimilars, respectively, in the management of RA. CONCLUSION: This survey has highlighted many areas of improvement in the practice of rheumatologists in Saudi Arabia and should be the focus of future educational activities. PMID- 26354410 TI - Developing Anticancer Copper(II) Pro-drugs Based on the Nature of Cancer Cells and the Human Serum Albumin Carrier IIA Subdomain. AB - To synergistically enhance the selectivity and efficiency of anticancer copper drugs, we proposed and built a model to develop anticancer copper pro-drugs based on the nature of human serum albumin (HSA) IIA subdomain and cancer cells. Three copper(II) compounds of a 2-hydroxy-1-naphthaldehyde benzoyl hydrazone Schiff base ligand in the presence pyridine, imidazole, or indazole ligands were synthesized (C1-C3). The structures of three HSA complexes revealed that the Cu compounds bind to the hydrophobic cavity in the HSA IIA subdomain. Among them, the pyridine and imidazole ligands of C1 and C2 are replaced by Lys199, and His242 directly coordinates with Cu(II). The indazole and Br ligands of C3 are replaced by Lys199 and His242, respectively. Compared with the Cu(II) compounds alone, the HSA complexes enhance cytotoxicity in MCF-7 cells approximately 3-5 fold, but do not raise cytotoxicity levels in normal cells in vitro through selectively accumulating in cancer cells to some extent. We find that the HSA complex has a stronger capacity for cell cycle arrest in the G2/M phase of MCF-7 by targeting cyclin-dependent kinase 1 (CDK1) and down-regulating the expression of CDK1 and cyclin B1. Moreover, the HSA complex promotes MCF-7 cell apoptosis possibly through the intrinsic reactive oxygen species (ROS) mediated mitochondrial pathway, accompanied by the regulation of Bcl-2 family proteins. PMID- 26354411 TI - Letter to the editor: Reply to Schillaci (2015): "Correlation between multiple variables among extant primates is insufficient for predicting unknown values in extinct hominins". PMID- 26354412 TI - How Much, How Often, How Long? Addressing Dosage in Intervention Studies. PMID- 26354414 TI - The pharmacokinetic-pharmacodynamic model of telmisartan and hydrochlorothiazide on blood pressure and plasma potassium after long-term administration in spontaneously hypertensive rats. AB - A pharmacokinetic-pharmacodynamic model was developed to describe the time course of blood pressure and plasma potassium after long-term telmisartan and/or hydrochlorothiazide administration in spontaneously hypertensive rats. The spontaneously hypertensive rats were administered once daily for 6 weeks. The drug concentration, blood pressure and plasma potassium were monitored for several points. The time courses of blood pressure and plasma potassium were described by indirect response pharmacokinetic-pharmacodynamic model. The synergistic antihypertensive pharmacodynamic interaction between telmisartan and hydrochlorothiazide was observed, which was simulated by the inhibitory function of telmisartan and stimulatory function of hydrochlorothiazide after co administration of the two drugs. For plasma potassium, when hydrochlorothiazide administrated alone, the plasma potassium reached to a low steady-state level at 4.64 mmol/L for 6 weeks. The plasma potassium increased to a steady-state level at 4.84 mmol/L after co-administration of telmisartan. The time courses of plasma potassium were successfully characterized by indirect response pharmacokinetic pharmacodynamic model after long-term administration of telmisartan and/or hydrochlorothiazide. The model captured turnovers of blood pressure and plasma potassium in the different time phases and dose conditions. PMID- 26354413 TI - Proton beam radiation induces DNA damage and cell apoptosis in glioma stem cells through reactive oxygen species. AB - Glioblastoma multiforme (GBM) is among the most lethal of human malignancies. Most GBM tumors are refractory to cytotoxic therapies. Glioma stem cells (GSCs) significantly contribute to GBM progression and post-treatment tumor relapse, therefore serving as a key therapeutic target; however, GSCs are resistant to conventional radiation therapy. Proton therapy is one of the newer cancer treatment modalities and its effects on GSCs function remain unclear. Here, by utilizing patient-derived GSCs, we show that proton radiation generates greater cytotoxicity in GSCs than x-ray photon radiation. Compared with photon radiation, proton beam irradiation induces more single and double strand DNA breaks, less H2AX phosphorylation, increased Chk2 phosphorylation, and reduced cell cycle recovery from G2 arrest, leading to caspase-3 activation, PARP cleavage, and cell apoptosis. Furthermore, proton radiation generates a large quantity of reactive oxygen species (ROS), which is required for DNA damage, cell cycle redistribution, apoptosis, and cytotoxicity. Together, these findings indicate that proton radiation has a higher efficacy in treating GSCs than photon radiation. Our data reveal a ROS-dependent mechanism by which proton radiation induces DNA damage and cell apoptosis in GSCs. Thus, proton therapy may be more efficient than conventional x-ray photon therapy for eliminating GSCs in GBM patients. PMID- 26354415 TI - Effect of frontal muscle aponeurosis flap suspension surgery for severe congenital ptosis in children. AB - OBJECTIVE: To investigate the effect of frontal muscle aponeurosis flap suspension surgery for severe congenital ptosis in children. METHODS: Recent results of 30 cases (45 eyes) of children with severe congenital ptosis were evaluated and follow-up observation was conducted. RESULTS: One week after the surgery, the success rate was 97.7% and it was 95.5% after three months. CONCLUSION: The suspension of frontal muscle aponeurosis should be the first choice for children with severe congenital ptosis for its simplicity, safety and fewer complications. PMID- 26354416 TI - Aluminum Trichloride Induces Hypertension and Disturbs the Function of Erythrocyte Membrane in Male Rats. AB - Aluminum (Al) is the most abundant metal in the earth's crust. Al accumulates in erythrocyte and causes toxicity on erythrocyte membrane. The dysfunction of erythrocyte membrane is a potential risk to hypertension. The high Al content in plasma was associated with hypertension. To investigate the effect of AlCl3 on blood pressure and the function of erythrocyte membrane, the rats were intragastrically exposed to 0, 64(1/20 LD50), 128(1/10 LD50), and 256(1/5 LD50) mg/kg body weight AlCl3 in double distilled water for 120 days, respectively. Then, we determined the systolic and mean arterial blood pressures of rats, the osmotic fragility, the percentage of membrane proteins, the activities of Na(+)/K(+)-ATPase, Mg(2+)-ATPase, Ca(2+)-ATPase, catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-pX), and malondialdehyde (MDA) content of the erythrocyte membrane in this experiment. The results showed that AlCl3 elevated the systolic and mean arterial blood pressure of rats, increased the osmotic fragility, decreased the percentage of membrane protein, inhibited the activities of Na(+)/K(+)-ATPase, Mg(2+)-ATPase, Ca(2+)-ATPase, CAT, SOD and GSH-pX, and increased the MDA content of erythrocyte membrane. These results indicate that AlCl3 may induce hypertension by disturbing the function of erythrocyte membrane. PMID- 26354417 TI - Centrin 3 is an inhibitor of centrosomal Mps1 and antagonizes centrin 2 function. AB - Centrins are a family of small, calcium-binding proteins with diverse cellular functions that play an important role in centrosome biology. We previously identified centrin 2 and centrin 3 (Cetn2 and Cetn3) as substrates of the protein kinase Mps1. However, although Mps1 phosphorylation sites control the function of Cetn2 in centriole assembly and promote centriole overproduction, Cetn2 and Cetn3 are not functionally interchangeable, and we show here that Cetn3 is both a biochemical inhibitor of Mps1 catalytic activity and a biological inhibitor of centrosome duplication. In vitro, Cetn3 inhibits Mps1 autophosphorylation at Thr 676, a known site of T-loop autoactivation, and interferes with Mps1-dependent phosphorylation of Cetn2. The cellular overexpression of Cetn3 attenuates the incorporation of Cetn2 into centrioles and centrosome reduplication, whereas depletion of Cetn3 generates extra centrioles. Finally, overexpression of Cetn3 reduces Mps1 Thr-676 phosphorylation at centrosomes, and mimicking Mps1-dependent phosphorylation of Cetn2 bypasses the inhibitory effect of Cetn3, suggesting that the biological effects of Cetn3 are due to the inhibition of Mps1 function at centrosomes. PMID- 26354418 TI - Cordon bleu promotes the assembly of brush border microvilli. AB - Microvilli are actin-based protrusions found on the surface of diverse cell types, where they amplify membrane area and mediate interactions with the external environment. In the intestinal tract, these protrusions play central roles in nutrient absorption and host defense and are therefore essential for maintaining homeostasis. However, the mechanisms controlling microvillar assembly remain poorly understood. Here we report that the multifunctional actin regulator cordon bleu (COBL) promotes the growth of brush border (BB) microvilli. COBL localizes to the base of BB microvilli via a mechanism that requires its proline rich N-terminus. Knockdown and overexpression studies show that COBL is needed for BB assembly and sufficient to induce microvillar growth using a mechanism that requires functional WH2 domains. We also find that COBL acts downstream of the F-BAR protein syndapin-2, which drives COBL targeting to the apical domain. These results provide insight into a mechanism that regulates microvillar growth during epithelial differentiation and have significant implications for understanding the maintenance of intestinal homeostasis. PMID- 26354419 TI - Meis3 is required for neural crest invasion of the gut during zebrafish enteric nervous system development. AB - During development, vagal neural crest cells fated to contribute to the enteric nervous system migrate ventrally away from the neural tube toward and along the primitive gut. The molecular mechanisms that regulate their early migration en route to and entry into the gut remain elusive. Here we show that the transcription factor meis3 is expressed along vagal neural crest pathways. Meis3 loss of function results in a reduction in migration efficiency, cell number, and the mitotic activity of neural crest cells in the vicinity of the gut but has no effect on neural crest or gut specification. Later, during enteric nervous system differentiation, Meis3-depleted embryos exhibit colonic aganglionosis, a disorder in which the hindgut is devoid of neurons. Accordingly, the expression of Shh pathway components, previously shown to have a role in the etiology of Hirschsprung's disease, was misregulated within the gut after loss of Meis3. Taken together, these findings support a model in which Meis3 is required for neural crest proliferation, migration into, and colonization of the gut such that its loss leads to severe defects in enteric nervous system development. PMID- 26354420 TI - Dynamic changes in CCAN organization through CENP-C during cell-cycle progression. AB - The kinetochore is a crucial structure for faithful chromosome segregation during mitosis and is formed in the centromeric region of each chromosome. The 16 subunit protein complex known as the constitutive centromere-associated network (CCAN) forms the foundation for kinetochore assembly on the centromeric chromatin. Although the CCAN can be divided into several subcomplexes, it remains unclear how CCAN proteins are organized to form the functional kinetochore. In particular, this organization may vary as the cell cycle progresses. To address this, we analyzed the relationship of centromeric protein (CENP)-C with the CENP H complex during progression of the cell cycle. We find that the middle portion of chicken CENP-C (CENP-C(166-324)) is sufficient for centromere localization during interphase, potentially through association with the CENP-L-N complex. The C-terminus of CENP-C (CENP-C(601-864)) is essential for centromere localization during mitosis, through binding to CENP-A nucleosomes, independent of the CENP-H complex. On the basis of these results, we propose that CCAN organization changes dynamically during progression of the cell cycle. PMID- 26354421 TI - Phosphorylation of the Scc2 cohesin deposition complex subunit regulates chromosome condensation through cohesin integrity. AB - The cohesion of replicated sister chromatids promotes chromosome biorientation, gene regulation, DNA repair, and chromosome condensation. Cohesion is mediated by cohesin, which is deposited on chromosomes by a separate conserved loading complex composed of Scc2 and Scc4 in Saccharomyces cerevisiae. Although it is known to be required, the role of Scc2/Scc4 in cohesin deposition remains enigmatic. Scc2 is a phosphoprotein, although the functions of phosphorylation in deposition are unknown. We identified 11 phosphorylated residues in Scc2 by mass spectrometry. Mutants of SCC2 with substitutions that mimic constitutive phosphorylation retain normal Scc2-Scc4 interactions and chromatin association but exhibit decreased viability, sensitivity to genotoxic agents, and decreased stability of the Mcd1 cohesin subunit in mitotic cells. Cohesin association on chromosome arms, but not pericentromeric regions, is reduced in the phosphomimetic mutants but remains above a key threshold, as cohesion is only modestly perturbed. However, these scc2 phosphomimetic mutants exhibit dramatic chromosome condensation defects that are likely responsible for their high inviability. From these data, we conclude that normal Scc2 function requires modulation of its phosphorylation state and suggest that scc2 phosphomimetic mutants cause an increased incidence of abortive cohesin deposition events that result in compromised cohesin complex integrity and Mcd1 turnover. PMID- 26354422 TI - Ccq1-Tpz1TPP1 interaction facilitates telomerase and SHREC association with telomeres in fission yeast. AB - Evolutionarily conserved shelterin complex is essential for telomere maintenance in the fission yeast Schizosaccharomyces pombe. Elimination of the fission yeast shelterin subunit Ccq1 causes progressive loss of telomeres due to the inability to recruit telomerase, activates the DNA damage checkpoint, and loses heterochromatin at telomere/subtelomere regions due to reduced recruitment of the heterochromatin regulator complex Snf2/histone deacetylase-containing repressor complex (SHREC). The shelterin subunit Tpz1(TPP1) directly interacts with Ccq1 through conserved C-terminal residues in Tpz1(TPP1), and tpz1 mutants that fail to interact with Ccq1 show telomere shortening, checkpoint activation, and loss of heterochromatin. While we have previously concluded that Ccq1-Tpz1(TPP1) interaction contributes to Ccq1 accumulation and telomerase recruitment based on analysis of tpz1 mutants that fail to interact with Ccq1, another study reported that loss of Ccq1-Tpz1(TPP1) interaction does not affect accumulation of Ccq1 or telomerase. Furthermore, it remained unclear whether loss of Ccq1-Tpz1(TPP1) interaction affects SHREC accumulation at telomeres. To resolve these issues, we identified and characterized a series of ccq1 mutations that disrupt Ccq1 Tpz1(TPP1) interaction. Characterization of these ccq1 mutants established that Ccq1-Tpz1(TPP1) interaction contributes to optimal binding of the Ccq1-SHREC complex, and is critical for Rad3(ATR)/Tel1(ATM)-dependent Ccq1 Thr93 phosphorylation and telomerase recruitment. PMID- 26354423 TI - Physical limits on kinesin-5-mediated chromosome congression in the smallest mitotic spindles. AB - A characteristic feature of mitotic spindles is the congression of chromosomes near the spindle equator, a process mediated by dynamic kinetochore microtubules. A major challenge is to understand how precise, submicrometer-scale control of kinetochore micro-tubule dynamics is achieved in the smallest mitotic spindles, where the noisiness of microtubule assembly/disassembly will potentially act to overwhelm the spatial information that controls microtubule plus end-tip positioning to mediate congression. To better understand this fundamental limit, we conducted an integrated live fluorescence, electron microscopy, and modeling analysis of the polymorphic fungal pathogen Candida albicans, which contains one of the smallest known mitotic spindles (<1 MUm). Previously, ScCin8p (kinesin-5 in Saccharomyces cerevisiae) was shown to mediate chromosome congression by promoting catastrophe of long kinetochore microtubules (kMTs). Using C. albicans yeast and hyphal kinesin-5 (Kip1p) heterozygotes (KIP1/kip1?), we found that mutant spindles have longer kMTs than wild-type spindles, consistent with a less organized spindle. By contrast, kinesin-8 heterozygous mutant (KIP3/kip3?) spindles exhibited the same spindle organization as wild type. Of interest, spindle organization in the yeast and hyphal states was indistinguishable, even though yeast and hyphal cell lengths differ by two- to fivefold, demonstrating that spindle length regulation and chromosome congression are intrinsic to the spindle and largely independent of cell size. Together these results are consistent with a kinesin-5-mediated, length-dependent depolymerase activity that organizes chromosomes at the spindle equator in C. albicans to overcome fundamental noisiness in microtubule self-assembly. More generally, we define a dimensionless number that sets a fundamental physical limit for maintaining congression in small spindles in the face of assembly noise and find that C. albicans operates very close to this limit, which may explain why it has the smallest known mitotic spindle that still manifests the classic congression architecture. PMID- 26354424 TI - Joint modeling of cell and nuclear shape variation. AB - Modeling cell shape variation is critical to our understanding of cell biology. Previous work has demonstrated the utility of nonrigid image registration methods for the construction of nonparametric nuclear shape models in which pairwise deformation distances are measured between all shapes and are embedded into a low dimensional shape space. Using these methods, we explore the relationship between cell shape and nuclear shape. We find that these are frequently dependent on each other and use this as the motivation for the development of combined cell and nuclear shape space models, extending nonparametric cell representations to multiple-component three-dimensional cellular shapes and identifying modes of joint shape variation. We learn a first-order dynamics model to predict cell and nuclear shapes, given shapes at a previous time point. We use this to determine the effects of endogenous protein tags or drugs on the shape dynamics of cell lines and show that tagged C1QBP reduces the correlation between cell and nuclear shape. To reduce the computational cost of learning these models, we demonstrate the ability to reconstruct shape spaces using a fraction of computed pairwise distances. The open-source tools provide a powerful basis for future studies of the molecular basis of cell organization. PMID- 26354425 TI - Small-molecule agonists of mammalian Diaphanous-related (mDia) formins reveal an effective glioblastoma anti-invasion strategy. AB - The extensive invasive capacity of glioblastoma (GBM) makes it resistant to surgery, radiotherapy, and chemotherapy and thus makes it lethal. In vivo, GBM invasion is mediated by Rho GTPases through unidentified downstream effectors. Mammalian Diaphanous (mDia) family formins are Rho-directed effectors that regulate the F-actin cytoskeleton to support tumor cell motility. Historically, anti-invasion strategies focused upon mDia inhibition, whereas activation remained unexplored. The recent development of small molecules directly inhibiting or activating mDia-driven F-actin assembly that supports motility allows for exploration of their role in GBM. We used the formin inhibitor SMIFH2 and mDia agonists IMM-01/-02 and mDia2-DAD peptides, which disrupt autoinhibition, to examine the roles of mDia inactivation versus activation in GBM cell migration and invasion in vitro and in an ex vivo brain slice invasion model. Inhibiting mDia suppressed directional migration and spheroid invasion while preserving intrinsic random migration. mDia agonism abrogated both random intrinsic and directional migration and halted U87 spheroid invasion in ex vivo brain slices. Thus mDia agonism is a superior GBM anti-invasion strategy. We conclude that formin agonism impedes the most dangerous GBM component-tumor spread into surrounding healthy tissue. Formin activation impairs novel aspects of transformed cells and informs the development of anti-GBM invasion strategies. PMID- 26354426 TI - HPV vaccination syndrome. A questionnaire-based study. AB - Isolated cases and small series have described the development of complex regional pain syndrome, postural orthostatic tachycardia, and fibromyalgia after human papillomavirus (HPV) vaccination. These illnesses are difficult to diagnose and have overlapping clinical features. Small fiber neuropathy and dysautonomia may play a major role in the pathogenesis of these entities. We used the following validated questionnaires to appraise the chronic illness that might appear after HPV vaccination: The 2010 American College of Rheumatology Fibromyalgia Diagnostic Criteria, COMPASS 31 dysautonomia questionnaire, and S LANSS neuropathic pain form. These questionnaires and a "present illness" survey were e-mailed to persons who had the onset of a chronic ailment soon after HPV vaccination. Forty-five filled questionnaires from individuals living in 13 different countries were collected in a month's period. Mean (+/-SD) age at vaccination time was 14 +/- 5 years. Twenty-nine percent of the cases had immediate (within 24 h) post-vaccination illness onset. The most common presenting complaints were musculoskeletal pain (66%), fatigue (57%), headache (57%), dizziness/vertigo (43%), and paresthesias/allodynia (36%). Fifty-three percent of affected individuals fulfill the fibromyalgia criteria. COMPASS-31 score was 43 +/- 21, implying advanced autonomic dysfunction. Eighty-three percent of the patients who had ongoing pain displayed S-LANSS values >12, suggesting a neuropathic component in their pain experience. After a mean period of 4.2 +/- 2.5 years post-vaccination, 93% of patients continue to have incapacitating symptoms and remain unable to attend school or work. In conclusion, a disabling syndrome of chronic neuropathic pain, fatigue, and autonomic dysfunction may appear after HPV vaccination. PMID- 26354427 TI - Entheseal involvement in systemic disorders. AB - The objective of this study is to review the data on entheseal involvement in systemic disorders. A Pubmed search utilizing the indexing terms "enthesis" and "enthesitis" was conducted and the data pertinent to the aim of the review was extracted and organized in accordance with the preplanned structure of the manuscript. A number of cadaver-based studies, as well as studies using ultrasonography and magnetic resonance imaging, have detailed new distinct aspects of enthesis physiology and pathology in a variety of rheumatic and non rheumatic systemic disorders. Major progress has been done in characterization of separate components of the enthesis organ, imaging of entheses, elaboration of the role and features of entheseal disease in spondyloarthropathies, juvenile idiopathic arthritis, osteoarthritis, familial Mediterranean fever, hyperuricemia, and other systemic conditions. The knowledge acquired and summarized herein shows that entheses can be affected in various ways in variety of medical disorders with different pathogenesis. Better understanding of the risk factors, mechanisms and natural history of enthesopathies is warranted. The current progress in the understanding of entheseal involvement in systemic disorders represents just the first step in resolving the entheses-related enigmas. PMID- 26354428 TI - Occult spondyloarthritis in inflammatory bowel disease. AB - Spondyloarthritis (SpA) is a frequent extra-intestinal manifestation in patients with inflammatory bowel disease (IBD), although its real diffusion is commonly considered underestimated. Abnormalities in the microbioma and genetic predisposition have been implicated in the link between bowel and joint inflammation. Otherwise, up to date, pathogenetic mechanisms are still largely unknown and the exact influence of the bowel activity on rheumatic manifestations is not clearly explained. Due to evidence-based results of clinical studies, the interest on clinically asymptomatic SpA in IBD patients increased in the last few years. Actually, occult enthesitis and sacroiliitis are discovered in high percentages of IBD patients by different imaging techniques, mainly enthesis ultrasound (US) and sacroiliac joint X-ray examinations. Several diagnostic approaches and biomarkers have been proposed in an attempt to correctly classify and diagnose clinically occult joint manifestations and to define clusters of risk for patient screening, although definitive results are still lacking. The correct recognition of occult SpA in IBD requires an integrated multidisciplinary approach in order to identify common diagnostic and therapeutic strategies. The use of inexpensive and rapid imaging techniques, such as US and X-ray, should be routinely included in daily clinical practice and trials to correctly evaluate occult SpA, thus preventing future disability and worsening of quality of life in IBD patients. PMID- 26354429 TI - Formaldehyde crosslinking: a tool for the study of chromatin complexes. AB - Formaldehyde has been used for decades to probe macromolecular structure and function and to trap complexes, cells, and tissues for further analysis. Formaldehyde crosslinking is routinely employed for detection and quantification of protein-DNA interactions, interactions between chromatin proteins, and interactions between distal segments of the chromatin fiber. Despite widespread use and a rich biochemical literature, important aspects of formaldehyde behavior in cells have not been well described. Here, we highlight features of formaldehyde chemistry relevant to its use in analyses of chromatin complexes, focusing on how its properties may influence studies of chromatin structure and function. PMID- 26354430 TI - The emerging role of nuclear viral DNA sensors. AB - Detecting pathogenic DNA by intracellular receptors termed "sensors" is critical toward galvanizing host immune responses and eliminating microbial infections. Emerging evidence has challenged the dogma that sensing of viral DNA occurs exclusively in sub-cellular compartments normally devoid of cellular DNA. The interferon-inducible protein IFI16 was shown to bind nuclear viral DNA and initiate immune signaling, culminating in antiviral cytokine secretion. Here, we review the newly characterized nucleus-originating immune signaling pathways, their links to other crucial host defenses, and unique mechanisms by which viruses suppress their functions. We frame these findings in the context of human pathologies associated with nuclear replicating DNA viruses. PMID- 26354431 TI - Rapid deamination of cyclobutane pyrimidine dimer photoproducts at TCG sites in a translationally and rotationally positioned nucleosome in vivo. AB - Sunlight-induced C to T mutation hot spots in skin cancers occur primarily at methylated CpG sites that coincide with sites of UV-induced cyclobutane pyrimidine dimer (CPD) formation. The C and 5-methyl-C in CPDs are not stable and deaminate to U and T, respectively, which leads to the insertion of A by the DNA damage bypass polymerase eta, thereby defining a probable mechanism for the origin of UV-induced C to T mutations. Deamination rates for T(m)CG CPDs have been found to vary 12-fold with rotational position in a nucleosome in vitro. To determine the influence of nucleosome structure on deamination rates in vivo, we determined the deamination rates of CPDs at TCG sites in a stably positioned nucleosome within the FOS promoter in HeLa cells. A procedure for in vivo hydroxyl radical footprinting with Fe-EDTA was developed, and, together with results from a cytosine methylation protection assay, we determined the translational and rotational positions of the TCG sites. Consistent with the in vitro observations, deamination was slower for one CPD located at an intermediate rotational position compared with two other sites located at outside positions, and all were much faster than for CPDs at non-TCG sites. Photoproduct formation was also highly suppressed at one site, possibly due to its interaction with a histone tail. Thus, it was shown that CPDs of TCG sites deaminate the fastest in vivo and that nucleosomes can modulate both their formation and deamination, which could contribute to the UV mutation hot spots and cold spots. PMID- 26354432 TI - The linker for activation of T cells (LAT) signaling hub: from signaling complexes to microclusters. AB - Since the cloning of the critical adapter, LAT (linker for activation of T cells), more than 15 years ago, a combination of multiple scientific approaches and techniques continues to provide valuable insights into the formation, composition, regulation, dynamics, and function of LAT-based signaling complexes. In this review, we will summarize current views on the assembly of signaling complexes nucleated by LAT. LAT forms numerous interactions with other signaling molecules, leading to cooperativity in the system. Furthermore, oligomerization of LAT by adapter complexes enhances intracellular signaling and is physiologically relevant. These results will be related to data from super resolution microscopy studies that have revealed the smallest LAT-based signaling units and nanostructure. PMID- 26354433 TI - Introduction to thematic series: protein interactions, structures, and networks. AB - Protein interactions are fundamental to the proper functioning of cells, and aberrant formation or regulation of protein interactions is at the heart of many diseases, including cancer. The advancement of methods to study the identity, function, and regulation of protein complexes makes possible the understanding of how those complexes malfunction in human diseases. New methodologies in mass spectrometry, microscopy, and protein structural analysis are rapidly advancing the amount and quality of the data, as well as the level of detail that can be obtained from experiments. With this progress, the questions that can be addressed and the biological landscape are changing. This series of minireviews highlights methodological advances and how they have been applied in novel ways to explore the function and regulation of pathways and dynamic networks in cells. PMID- 26354434 TI - Mismatch repair. AB - Highly conserved MutS homologs (MSH) and MutL homologs (MLH/PMS) are the fundamental components of mismatch repair (MMR). After decades of debate, it appears clear that the MSH proteins initiate MMR by recognizing a mismatch and forming multiple extremely stable ATP-bound sliding clamps that diffuse without hydrolysis along the adjacent DNA. The function(s) of MLH/PMS proteins is less clear, although they too bind ATP and are targeted to MMR by MSH sliding clamps. Structural analysis combined with recent real-time single molecule and cellular imaging technologies are providing new and detailed insight into the thermal driven motions that animate the complete MMR mechanism. PMID- 26354436 TI - The Interferon-induced Transmembrane Proteins, IFITM1, IFITM2, and IFITM3 Inhibit Hepatitis C Virus Entry. AB - The interferon-induced transmembrane (IFITM) family of proteins have recently been identified as important host effector molecules of the type I interferon response against viruses. IFITM1 has been identified as a potent antiviral effector against hepatitis C virus (HCV), whereas the related family members IFITM2 and IFITM3 have been described to have antiviral effects against a broad range of RNA viruses. Here, we demonstrate that IFITM2 and IFITM3 play an integral role in the interferon response against HCV and act at the level of late entry stages of HCV infection. We have established that in hepatocytes, IFITM2 and IFITM3 localize to the late and early endosomes, respectively, as well as the lysosome. Furthermore, we have demonstrated that S-palmitoylation of all three IFITM proteins is essential for anti-HCV activity, whereas the conserved tyrosine residue in the N-terminal domain of IFITM2 and IFITM3 plays a significant role in protein localization. However, this tyrosine was found to be dispensable for anti HCV activity, with mutation of the tyrosine resulting in an IFITM1-like phenotype with the retention of anti-HCV activity and co-localization of IFITM2 and IFITM3 with CD81. In conclusion, we propose that the IFITM proteins act in a coordinated manner to restrict HCV infection by targeting the endocytosed HCV virion for lysosomal degradation and demonstrate that the actions of the IFITM proteins are indeed virus and cell-type specific. PMID- 26354435 TI - Proteinase-activated receptor 2 promotes cancer cell migration through RNA methylation-mediated repression of miR-125b. AB - Proteinase activated-receptor 2 (PAR2) participates in cancer metastasis promoted by serine proteinases. The current study aimed to test the molecular mechanism by which PAR2 promotes cancer cell migration. In different cancer cells, activation of PAR2 by activating peptide (PAR2-AP) dramatically increased cell migration, whereas knock down of PAR2 inhibited cellular motility. The PAR2 activation also repressed miR-125b expression while miR-125b mimic successfully blocked PAR2 induced cell migration. Moreover, Grb associated-binding protein 2 (Gab2) was identified as a novel target gene of miR-125b and it mediated PAR2-induced cell migration. The correlation of PAR2 with miR-125b and Gab2 was further supported by the findings obtained from human colorectal carcinoma specimens. Remarkably, knock down of NOP2/Sun domain family, member 2 (NSun2), a RNA methyltransferase, blocked the reduction in miR-125b induced by PAR2. Furthermore, PAR2 activation increased the level of N(6)-methyladenosine (m(6)A)-containing pre-miR-125b in NSun2-dependent manner. Taken together, our results demonstrated that miR-125b mediates PAR2-induced cancer cell migration by targeting Gab2 and that NSun2 dependent RNA methylation contributes to the down-regulation of miR-125b by PAR2 signaling. These findings suggest a novel epigenetic mechanism by which microenvironment regulates cancer cell migration by altering miRNA expression. PMID- 26354437 TI - Specific chaperones and regulatory domains in control of amyloid formation. AB - Many proteins can form amyloid-like fibrils in vitro, but only about 30 amyloids are linked to disease, whereas some proteins form physiological amyloid-like assemblies. This raises questions of how the formation of toxic protein species during amyloidogenesis is prevented or contained in vivo. Intrinsic chaperoning or regulatory factors can control the aggregation in different protein systems, thereby preventing unwanted aggregation and enabling the biological use of amyloidogenic proteins. The molecular actions of these chaperones and regulators provide clues to the prevention of amyloid disease, as well as to the harnessing of amyloidogenic proteins in medicine and biotechnology. PMID- 26354439 TI - Producing glucose 6-phosphate from cellulosic biomass: structural insights into levoglucosan bioconversion. AB - The most abundant carbohydrate product of cellulosic biomass pyrolysis is the anhydrosugar levoglucosan (1,6-anhydro-beta-d-glucopyranose), which can be converted to glucose 6-phosphate by levoglucosan kinase (LGK). In addition to the canonical kinase phosphotransfer reaction, the conversion requires cleavage of the 1,6-anhydro ring to allow ATP-dependent phosphorylation of the sugar O6 atom. Using x-ray crystallography, we show that LGK binds two magnesium ions in the active site that are additionally coordinated with the nucleotide and water molecules to result in ideal octahedral coordination. To further verify the metal binding sites, we co-crystallized LGK in the presence of manganese instead of magnesium and solved the structure de novo using the anomalous signal from four manganese atoms in the dimeric structure. The first metal is required for catalysis, whereas our work suggests that the second is either required or significantly promotes the catalytic rate. Although the enzyme binds its sugar substrate in a similar orientation to the structurally related 1,6-anhydro-N acetylmuramic acid kinase (AnmK), it forms markedly fewer bonding interactions with the substrate. In this orientation, the sugar is in an optimal position to couple phosphorylation with ring cleavage. We also observed a second alternate binding orientation for levoglucosan, and in these structures, ADP was found to bind with lower affinity. These combined observations provide an explanation for the high Km of LGK for levoglucosan. Greater knowledge of the factors that contribute to the catalytic efficiency of LGK can be used to improve applications of this enzyme for levoglucosan-derived biofuel production. PMID- 26354438 TI - Lateral diffusion, function, and expression of the slow channel congenital myasthenia syndrome alphaC418W nicotinic receptor mutation with changes in lipid raft components. AB - Lipid rafts, specialized membrane microdomains in the plasma membrane rich in cholesterol and sphingolipids, are hot spots for a number of important cellular processes. The novel nicotinic acetylcholine receptor (nAChR) mutation alphaC418W, the first lipid-exposed mutation identified in a patient that causes slow channel congenital myasthenia syndrome was shown to be cholesterol-sensitive and to accumulate in microdomains rich in the membrane raft marker protein caveolin-1. The objective of this study is to gain insight into the mechanism by which lateral segregation into specialized raft membrane microdomains regulates the activable pool of nAChRs. We performed fluorescent recovery after photobleaching (FRAP), quantitative RT-PCR, and whole cell patch clamp recordings of GFP-encoding Mus musculus nAChRs transfected into HEK 293 cells to assess the role of cholesterol and caveolin-1 (CAV-1) in the diffusion, expression, and functionality of the nAChR (WT and alphaC418W). Our findings support the hypothesis that a cholesterol-sensitive nAChR might reside in specialized membrane microdomains that upon cholesterol depletion become disrupted and release the cholesterol-sensitive nAChRs to the pool of activable receptors. In addition, our results in HEK 293 cells show an interdependence between CAV-1 and alphaC418W that could confer end plates rich in alphaC418W nAChRs to a susceptibility to changes in cholesterol levels that could cause adverse drug reactions to cholesterol-lowering drugs such as statins. The current work suggests that the interplay between cholesterol and CAV-1 provides the molecular basis for modulating the function and dynamics of the cholesterol-sensitive alphaC418W nAChR. PMID- 26354440 TI - Using protein motion to read, write, and erase ubiquitin signals. AB - Eukaryotes use a tiny protein called ubiquitin to send a variety of signals, most often by post-translationally attaching ubiquitins to substrate proteins and to each other, thereby forming polyubiquitin chains. A combination of biophysical, biochemical, and biological studies has shown that complex macromolecular dynamics are central to many aspects of ubiquitin signaling. This review focuses on how equilibrium fluctuations and coordinated motions of ubiquitin itself, the ubiquitin conjugation machinery, and deubiquitinating enzymes enable activity and regulation on many levels, with implications for how such a tiny protein can send so many signals. PMID- 26354441 TI - Structure and function of the Escherichia coli Tol-Pal stator protein TolR. AB - TolR is a 15-kDa inner membrane protein subunit of the Tol-Pal complex in Gram negative bacteria, and its function is poorly understood. Tol-Pal is recruited to cell division sites where it is involved in maintaining the integrity of the outer membrane. TolR is related to MotB, the peptidoglycan (PG)-binding stator protein from the flagellum, suggesting it might serve a similar role in Tol-Pal. The only structure thus far reported for TolR is of the periplasmic domain from Haemophilus influenzae in which N- and C-terminal residues had been deleted (TolR(62-133), Escherichia coli numbering). H. influenzae TolR(62-133) is a symmetrical dimer with a large deep cleft at the dimer interface. Here, we present the 1.7-A crystal structure of the intact periplasmic domain of E. coli TolR (TolR(36-142)). E. coli TolR(36-142) is also dimeric, but the architecture of the dimer is radically different from that of TolR(62-133) due to the intertwining of its N and C termini. TolR monomers are rotated ~180 degrees relative to each other as a result of this strand swapping, obliterating the putative PG-binding groove seen in TolR(62-133). We found that removal of the strand-swapped regions (TolR(60-133)) exposes cryptic PG binding activity that is absent in the full-length domain. We conclude that to function as a stator in the Tol-Pal complex dimeric TolR must undergo large scale structural remodeling reminiscent of that proposed for MotB, where the N- and C-terminal sequences unfold in order for the protein to both reach and bind the PG layer ~90 A away from the inner membrane. PMID- 26354442 TI - Effect of purple loosestrife (Lythrum salicaria) diet supplementation in rabbit nutrition on performance, digestibility, health and meat quality. AB - In this study, 160 Hycole weaned rabbits (35 days old) were randomly divided into four groups of 40. The rabbits were studied throughout a 54-day experimentation period in order to determine the impact of dietary supplementation from herbs composed of 0.2%, 0.4% dry ground Lythrum salicaria leaves (LS) and 0.3% Cunirel((r)) (CR; a commercial herb mixture containing LS as the main ingredient) on performance, digestibility, health and meat quality. The basal diet was given to the control group. No significant differences were found in performance, 10 rabbits from each group were selected for evaluation regarding apparent digestibility. The rabbits fed the control diet and the diet with the low level of LS had a higher level of CP digestibility than did the animals that were supplemented with the high LS levels and CR (85.7% and 84.9% v. 84.0% and 84.0%, respectively; P<0.05). The ether extract digestibility was lower in the treatment group with 0.4%LS addition and CR as compared with the control group (52.2% and 54.5% v. 62.6%, respectively; P<0.05). The slaughter process was performed on 89 day-old rabbits to study the carcass characteristics, meat quality, blood parameters, caecal contents and gut histology. The total leukocyte counts in the control animals were lower than they were in the rabbits fed 0.2%, 0.4%LS and CR (4.06 v. 8.25, 8.63 and 8.21*10(9)/l, respectively; P<0.05). For caecal fermentation, the caecal contents of the rabbits fed 0.4% of LS, showed higher concentrations of total volatile fatty acid (VFA; 24.1 v. 18.9 mg/kg dry matter (DM); P<0.05) and acetic acid (18.3 v. 14.4 mg/kg DM; P<0.05), but lower ammonia levels (594 v. 892 mg/kg DM; P<0.05) as compared with the control group. PCR denaturing gradient gel electrophoresis analyses were performed to evaluate the microbial community in hard faeces, collected at days 35, 42, 49, 56, 70 and 89, whereas the caecal contents were taken after slaughtering. The results demonstrated that between the treatment groups, the similarity of the microbial communities was higher as compared with the control group. Moreover, only age was shown to influence microbiota diversity. In conclusion, the results of this study indicated that supplementation of LS in rabbit diets leads to an increase in the total white blood cells, total VFA and acetic acid concentration, and a decrease in the ammonia levels, as well as the digestibility when CR and high level of LS were supplemented, without causing any adverse effects on other parameters. PMID- 26354443 TI - Effect of prism adaptation on thermoregulatory control in humans. AB - The physiological regulation of skin temperature can be modulated not only by autonomic brain regions, but also by a network of higher-level cortical areas involved in the maintenance of a coherent representation of the body. In this study we assessed in healthy participants if the sensorimotor changes taking place during motor adaptation to the lateral displacement of the visual scene induced by wearing prismatic lenses (prism adaptation, PA), and the aftereffects, after prisms' removal, on the ability to process spatial coordinates, were associated with skin temperature regulation changes. We found a difference in thermoregulatory control as a function of the direction of the prism-induced displacement of the visual scene, and the subsequent sensorimotor adaptation. After PA to rightward displacing lenses, with leftward aftereffects (the same directional procedure efficaciously used for ameliorating left spatial neglect in right-brain-damaged patients) the hands' temperature decreased. Conversely, after adaptation to neutral lenses, and PA to leftward displacing lenses, with rightward aftereffects, the temperature of both hands increased. These results suggest a lateral asymmetry in the effects of PA on skin temperature regulation, and a relationship between body spatial representations and homeostatic control in humans. PMID- 26354445 TI - Money matters. PMID- 26354444 TI - Resection of bulky chromophobe renal cell carcinoma resolved severe idiopathic thrombocytopenic purpura: A case report. AB - Idiopathic thrombocytopenic purpura associated with renal cell carcinoma is relatively rare. We report the case of a 48-year-old woman with massive renal cell carcinoma, measuring approximately 20 * 14 * 14 cm, who presented with severe thrombocytopenia: platelet count, 2000 cells/MUL. After confirming normal bone marrow, she received high-dose dexamethasone and intravenous gamma globulin, which raised the platelet count to normal levels. She then underwent left radical nephrectomy. The pathological examination showed chromophobe renal cell carcinoma. After the resection, the platelet count was maintained within the normal range without any treatment. The current case is the first report of chromophobe renal cell carcinoma causative of severe idiopathic thrombocytopenic purpura. PMID- 26354446 TI - Keep a welcome. PMID- 26354447 TI - Loaded language. PMID- 26354448 TI - Reproducibility will not cure what ails science. PMID- 26354460 TI - Autopsies reveal signs of Alzheimer's in growth-hormone patients. PMID- 26354462 TI - Online security braces for quantum revolution. PMID- 26354461 TI - US agencies plan research-ethics overhaul. PMID- 26354463 TI - Germany claims success for elite universities drive. PMID- 26354464 TI - Trillions of trees. PMID- 26354465 TI - The revolution will not be crystallized: a new method sweeps through structural biology. PMID- 26354466 TI - Fishing for the first Americans. PMID- 26354467 TI - Climate change: Track urban emissions on a human scale. PMID- 26354468 TI - Gender balance: Women are funded more fairly in social science. PMID- 26354471 TI - Q&A: The academic satirist. PMID- 26354472 TI - Safety regulations: More extensive tests for e-cigarettes. PMID- 26354473 TI - Ocean acidification: Laboratory seawater studies are justified. PMID- 26354474 TI - Sustainable production: Physicists' report on EU green electricity. PMID- 26354475 TI - China: Outdated listing puts species at risk. PMID- 26354476 TI - Cell biology: Countercurrents in lipid flow. PMID- 26354478 TI - Neurodegeneration: Amyloid-beta pathology induced in humans. PMID- 26354479 TI - Atmospheric science: Sea-spray particles cause freezing in clouds. PMID- 26354480 TI - Astrophysics: Glimpse into a primitive stellar nursery. PMID- 26354481 TI - Dense cloud cores revealed by CO in the low metallicity dwarf galaxy WLM. AB - Understanding stellar birth requires observations of the clouds in which they form. These clouds are dense and self-gravitating, and in all existing observations they are molecular, with H2 the dominant species and carbon monoxide (CO) the best available tracer. When the abundances of carbon and oxygen are low compared with that of hydrogen, and the opacity from dust is also low, as in primeval galaxies and local dwarf irregular galaxies, CO forms slowly and is easily destroyed, so it is difficult for it to accumulate inside dense clouds. Here we report interferometric observations of CO clouds in the local group dwarf irregular galaxy Wolf-Lundmark-Melotte (WLM), which has a metallicity that is 13 per cent of the solar value and 50 per cent lower than the previous CO detection threshold. The clouds are tiny compared to the surrounding atomic and H2 envelopes, but they have typical densities and column densities for CO clouds in the Milky Way. The normal CO density explains why star clusters forming in dwarf irregulars have similar densities to star clusters in giant spiral galaxies. The low cloud masses suggest that these clusters will also be low mass, unless some galaxy-scale compression occurs, such as an impact from a cosmic cloud or other galaxy. If the massive metal-poor globular clusters in the halo of the Milky Way formed in dwarf galaxies, as is commonly believed, then they were probably triggered by such an impact. PMID- 26354482 TI - A marine biogenic source of atmospheric ice-nucleating particles. AB - The amount of ice present in clouds can affect cloud lifetime, precipitation and radiative properties. The formation of ice in clouds is facilitated by the presence of airborne ice-nucleating particles. Sea spray is one of the major global sources of atmospheric particles, but it is unclear to what extent these particles are capable of nucleating ice. Sea-spray aerosol contains large amounts of organic material that is ejected into the atmosphere during bubble bursting at the organically enriched sea-air interface or sea surface microlayer. Here we show that organic material in the sea surface microlayer nucleates ice under conditions relevant for mixed-phase cloud and high-altitude ice cloud formation. The ice-nucleating material is probably biogenic and less than approximately 0.2 micrometres in size. We find that exudates separated from cells of the marine diatom Thalassiosira pseudonana nucleate ice, and propose that organic material associated with phytoplankton cell exudates is a likely candidate for the observed ice-nucleating ability of the microlayer samples. Global model simulations of marine organic aerosol, in combination with our measurements, suggest that marine organic material may be an important source of ice-nucleating particles in remote marine environments such as the Southern Ocean, North Pacific Ocean and North Atlantic Ocean. PMID- 26354485 TI - Cori meets Dobzhansky: Evolution and Gene Expression in St. Louis: A report on the "Evolution and Core Processes in Gene Regulation" meeting in St. Louis, June 25-28, 2015. AB - St. Louis and its famous Gateway Arch were the setting of the Special Symposium: Evolution and Core Processes in Gene Regulation, sponsored by the American Society for Biochemistry and Molecular Biology. Biochemists and evolutionary biologists highlighted growing connections between studies of biochemical mechanism and natural selection on gene expression. PMID- 26354483 TI - Evidence for human transmission of amyloid-beta pathology and cerebral amyloid angiopathy. AB - More than two hundred individuals developed Creutzfeldt-Jakob disease (CJD) worldwide as a result of treatment, typically in childhood, with human cadaveric pituitary-derived growth hormone contaminated with prions. Although such treatment ceased in 1985, iatrogenic CJD (iCJD) continues to emerge because of the prolonged incubation periods seen in human prion infections. Unexpectedly, in an autopsy study of eight individuals with iCJD, aged 36-51 years, in four we found moderate to severe grey matter and vascular amyloid-beta (Abeta) pathology. The Abeta deposition in the grey matter was typical of that seen in Alzheimer's disease and Abeta in the blood vessel walls was characteristic of cerebral amyloid angiopathy and did not co-localize with prion protein deposition. None of these patients had pathogenic mutations, APOE epsilon4 or other high-risk alleles associated with early-onset Alzheimer's disease. Examination of a series of 116 patients with other prion diseases from a prospective observational cohort study showed minimal or no Abeta pathology in cases of similar age range, or a decade older, without APOE epsilon4 risk alleles. We also analysed pituitary glands from individuals with Abeta pathology and found marked Abeta deposition in multiple cases. Experimental seeding of Abeta pathology has been previously demonstrated in primates and transgenic mice by central nervous system or peripheral inoculation with Alzheimer's disease brain homogenate. The marked deposition of parenchymal and vascular Abeta in these relatively young patients with iCJD, in contrast with other prion disease patients and population controls, is consistent with iatrogenic transmission of Abeta pathology in addition to CJD and suggests that healthy exposed individuals may also be at risk of iatrogenic Alzheimer's disease and cerebral amyloid angiopathy. These findings should also prompt investigation of whether other known iatrogenic routes of prion transmission may also be relevant to Abeta and other proteopathic seeds associated with neurodegenerative and other human diseases. PMID- 26354486 TI - Differential contribution of Ih to the integration of excitatory synaptic inputs in substantia nigra pars compacta and ventral tegmental area dopaminergic neurons. AB - The selective vulnerability of substantia nigra pars compacta (SNc) dopaminergic (DA) neurons is an enigmatic trait of Parkinson's disease (PD), especially if compared to the remarkable resistance of closely related DA neurons in the neighboring ventral tegmental area (VTA). Overall evidence indicates that specific electrophysiological, metabolic and molecular factors underlie SNc vulnerability, although many pieces of the puzzle are still missing. In this respect, we recently demonstrated that 1-methyl-4-phenylpyridinium (MPP+), the active metabolite of the parkinsonizing toxin 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP), alters the electrophysiological properties of SNc DA neurons in vitro by inhibiting the hyperpolarization-activated current (Ih). Here, we present an electrophysiological investigation of the functional role of Ih in the integration of synaptic inputs in identified SNc and VTA DA neurons, comparatively, in acute midbrain slices from TH-GFP mice. We show that pharmacological suppression of Ih increases the amplitude and decay time of excitatory postsynaptic potentials, leading to temporal summation of multiple excitatory potentials at somatic level. Importantly, these effects are quantitatively more evident in SNc DA neurons. We conclude that Ih regulates the responsiveness to excitatory synaptic transmission in SNc and VTA DA neurons differentially. Finally, we present the hypothesis that Ih loss of function may be linked to PD trigger mechanisms, such as mitochondrial failure and ATP depletion, and act in concert with SNc-specific synaptic connectivity to promote selective vulnerability. PMID- 26354487 TI - Emerging Therapies for Osteoporosis. AB - Although several effective therapies are available for the treatment of osteoporosis in postmenopausal women and older men, there remains a need for the development of even more effective and acceptable drugs. Several new drugs that are in late-stage clinical development will be discussed. Abaloparatide (recombinant parathyroid hormone related peptide [PTHrP] analogue) has anabolic activity like teriparatide. Recent data from the phase 3 fracture prevention trial demonstrate that this agent is effective in reducing fracture risk. Inhibiting cathepsin K reduces bone resorption without decreasing the numbers or activity of osteoclasts, thereby preserving or promoting osteoblast function. Progressive increases in bone mineral density (BMD) have been observed over 5 years. Early data suggest that odanacatib effectively reduces fracture risk. Lastly, inhibiting sclerostin with humanized antibodies promotes rapid, substantial but transient increases in bone formation while inhibiting bone resorption. Marked increases in BMD have been observed in phase 2 studies. Fracture prevention studies are underway. The new therapies with novel and unique mechanisms of action may, alone or in combination, provide more effective treatment options for our patients. PMID- 26354488 TI - A 5-Year Prospective Follow-Up Study of Lipid-Rich Adrenal Incidentalomas: No Tumor Growth or Development of Hormonal Hypersecretion. AB - BACKGROUND: Current guidelines for follow-up of adrenal incidentalomas are extensive and hampered by lack of follow-up studies. We tested the hypothesis that small lipid-rich adrenal incidentalomas, initially characterized by tumor size <40 mm and <10 Hounsfield units (HUs) on unenhanced computed tomography (CT) may not demonstrate excessive growth/hormonal hypersecretion on follow-up. METHODS: Sixty-nine incidentalomas in 56 patients were restudied with unenhanced CT and screening for hypercortisolism (dexamethasone suppression test [DST], plasma adrenocorticotropic hormone) and pheochromocytoma (24-hour urinary metanephrines and normetanephrines) 5 years later. Primary hyperaldosteronism was excluded at base-line. RESULTS: Tumor (n=69) size was similar before and after 5 years follow-up (19+/-6 mm vs. 20+/-7 mm). Mean tumor growth was 1+/-2 mm. Largest increase in tumor size was 8 mm, this tumor was surgically removed and histopathology confirmed cortical adenoma. DST was normal in 54 patients and two patients (3.6%) were still characterized by subclinical hypercortisolism. Initial tumor size was >20 mm for the patient with largest tumor growth and those with subclinical hypercortisolism. All patients had normal 24-hour urinary metanephrines and normetanephrines. Low attenuation (<10 HU) was demonstrated in 97% of 67 masses re-evaluated with unenhanced CT. CONCLUSION: None of the patients developed clinically relevant tumor growth or new subclinical hypercortisolism. Biochemical screening for pheochromocytoma in incidentalomas demonstrating <10 HU on unenhanced CT is not needed. For such incidentalomas <40 mm, it seems sufficient to perform control CT and screen for hypercortisolism after 5 years. PMID- 26354489 TI - Allgrove (Triple A) Syndrome: A Case Report from the Kashmir Valley. AB - Allgrove (Triple A) syndrome is a rare autosomal recessive disorder characterized by cardinal features of adrenal insufficiency due to adrenocorticotropic hormone (ACTH) resistance, achalasia, and alacrimia. It is frequently associated with neurological manifestations like polyneuropathy. Since its first description by Allgrove in 1978, approximately 100 cases have been reported in the literature. Here we report an 18-year-old boy diagnosed as having Allgrove syndrome, with ACTH resistant adrenal insufficiency, achalasia, alacrimia, and severe motor polyneuropathy. Alacrimia was the earliest feature evident at the age of 8 years. He presented with achalasia and adrenal insufficiency at 12 and 18 years respectively and developed neurological symptoms in the form of severe muscle wasting at the age of 15 years. Patients with Allgrove syndrome usually manifest adrenal insufficiency and achalasia during first decade of life. Our patient manifested adrenal insufficiency and achalasia in the second decade and manifested neurological dysfunction before adrenal dysfunction. PMID- 26354490 TI - Subclinical Atherosclerosis in Patients with Cushing Syndrome: Evaluation with Carotid Intima-Media Thickness and Ankle-Brachial Index. AB - BACKGROUND: Cushing syndrome (CS) has been described as a killing disease due its cardiovascular complications. In fact, chronic cortisol excess leads to a constellation of complications, including hypertension, hyperglycemia, adiposity, and thromboembolism. The main vascular alteration associated with CS is atherosclerosis. METHODS: Aim of this study was to analyze carotid intima-media thickness (cIMT) and ankle-brachial index (ABI), two surrogate markers of subclinical atherosclerosis in a consecutive series of CS patients, compared to patients with essential hypertension (EH) and health subjects (HS). RESULTS: Patients with CS showed a significant increase (P<0.05) of cIMT (0.89+/-0.17 mm) compared to EH (0.81+/-0.16 mm) and HS (0.75+/-0.4 mm), with a high prevalence of plaque (23%; P<0.03). Moreover, CS patients showed a mean ABI values (1.07+/ 0.02) significantly lower respect to HS (1.12+/-0.11; P<0.05), and a higher percentage (20%) of pathological values of ABI (<=0.9; P<0.03). CONCLUSION: In conclusion, we confirmed and extended the data of cIMT in CS, and showed that the ABI represent another surrogate marker of subclinical atherosclerosis in this disease. PMID- 26354491 TI - Association of the Preoperative Neutrophil-to-ymphocyte Count Ratio and Platelet to-Lymphocyte Count Ratio with Clinicopathological Characteristics in Patients with Papillary Thyroid Cancer. AB - BACKGROUND: Several inflammatory biomarkers, especially a high preoperative neutrophil-to-lymphocyte count ratio (NLR) and platelet-to-lymphocyte count ratio (PLR), are known to be indicator of poor prognosis in several cancers. However, very few studies have evaluated the significance of the NLR and PLR in papillary thyroid cancer (PTC). We evaluated the association of the preoperative NLR and PLR with clinicopathological characteristics in patients with PTC. METHODS: This study included 1,066 female patients who underwent total thyroidectomy for PTC. Patients were stratified into 4 quartiles by preoperative NLR and PLR. And the combination of preoperative NLR and PLR was calculated on the basis of data obtained value of tertile as follows: patients with both an elevated PLR and an elevated NLR were allocated a score of 2, and patients showing one or neither were allocated a score of 1 or 0, respectively. RESULTS: The preoperative NLR and PLR were significantly lower in patients aged >=45 years and in patients with Hashimoto's thyroiditis. The PLR was significantly higher in patients with tumor size >1 cm (P=0.021).When the patients were categorized into the aforementioned four groups, the group with the higher preoperative PLR was found to have a significantly increased incidence of lateral lymph node metastasis (LNM) (P=0.018). However, there are no significant association between the combination of preoperative NLR and PLR and prognostic factors in PTC patients. CONCLUSION: These results suggest that a preoperative high PLR were significant associated with lateral LNM in female patients with PTC. PMID- 26354492 TI - Clinical Characteristics of Subjects with Sulfonylurea-Dependent Type 2 Diabetes. AB - BACKGROUND: Even though several oral anti-diabetic drugs (OAD) with various modes of action are replacing sulfonylurea (SU), some patients seem to be dependent on SU for adequate glycemic control. Therefore, we evaluated the clinical characteristics of such patients. METHODS: We selected the patients with type 2 diabetes who met following criteria from 2009 to 2014 at Seoul National University Hospital: glycated hemoglobin (HbA1c) was maintained below 7.5% for at least 6 months under small dose of SU (glimepiride <=2 mg/day or equivalent dose); after discontinuation of SU, HbA1c increased >=1.2% within 3 months or >=1.5% within 6 months; and after resuming SU, HbA1c reduction was >=0.8% or reduction of fasting plasma glucose was >=40 mg/dL within 3 months. Patients with impaired hepatic or renal function, and steroid users were excluded. RESULTS: Nineteen subjects were enrolled: after averaged 4.8+/-1.5 months of SU-free period, HbA1c increased from 6.7%+/-0.4% to 8.8%+/-0.8% even though adding other OAD such as gliptins. However, HbA1c decreased to 7.4%+/-0.7% after resuming SU within 2.4+/-0.8 months. There was no sexual predominance. Despite their old age (67+/-11 years) and long duration of diabetes (18+/-10 years), fasting C-peptide was relatively well-reserved (3.9+/-2.6 ng/mL), and nephropathy was not observed (albumin-creatinine ratio 21.2+/-16.6 mg/g and estimated glomerular filtration rate 75.8+/-18.0 mL/min/1.73 m2). Strong family history was also noted (73.7%). CONCLUSION: Despite hypoglycemia risk of SU, it seemed indispensable for a subset of patients with regard to insulin secretion. Genetic influences would be evaluated. PMID- 26354493 TI - Primary Hyperparathyroidism with Extensive Brown Tumors and Multiple Fractures in a 20-Year-Old Woman. AB - A brown tumor is a benign fibrotic, erosive bony lesion caused by localized, rapid osteoclastic turnover, resulting from hyperparathyroidism. Although brown tumors are one of the most pathognomonic signs of primary hyperparathyroidism, they are rarely seen in clinical practice. In this report, we present a case of 20-year-old woman with recurrent fractures and bone pain. Plain digital radiographs of the affected bones revealed multiple erosive bone tumors, which were finally diagnosed as brown tumors associated with primary hyperparathyroidism due to a parathyroid adenoma. This case shows that multiple, and clinically severe form of brown tumors can even occur in young patients. PMID- 26354494 TI - Characterization of Patients with Type 2 Diabetes according to Body Mass Index: Korea National Health and Nutrition Examination Survey from 2007 to 2011. AB - BACKGROUND: The present study aimed to investigate the clinical characteristics of type 2 diabetes mellitus (T2DM) in Korean adults according to body mass index (BMI) and to analyze the association with cardiovascular disease (CVD). METHODS: We conducted a cross-sectional study of data from the Korea National Health and Nutrition Examination Survey from 2007 to 2011. A total of 3,370 patients with T2DM were divided into categories according to BMI. We conducted a comparison of the T2DM patient population composition by BMI category between different countries. We investigated the prevalence of awareness, treatment, and target control of T2DM according to BMI. RESULTS: Patients with T2DM had a higher BMI, and were more likely to have a history of CVD than healthy controls. For Korean adults with T2DM, 8% had BMI >=30 kg/m2. By contrast, the population of patients with T2DM and BMI >=30 kg/m2 was 72% in patients in the USA and 56% in the UK. The rate of recognition, treatment, and control has worsened in parallel with increasing BMI. Even in patients with BMI 25 to 29.9 kg/m2, the prevalence of CVD or high risk factors for CVD was significantly higher than in patients with BMI 18.5 to 22.9 kg/m2 (odds ratio, 2.07). CONCLUSION: Korean patients with T2DM had lower BMI than those in Western countries. Higher BMI was associated with lower awareness, treatment, and control of diabetes, and a positive association was observed between CVD or high risk factors for CVD and BMI, even for patients who were overweight but not obese. PMID- 26354495 TI - The Children's Loneliness Scale. AB - The present study examined the factor structure and construct validity of the Children's Loneliness Scale (CLS), a popular measure of childhood loneliness, in Belgian children. Analyses were conducted on two samples of fifth and sixth graders in Belgium, for a total of 1,069 children. A single-factor structure proved superior to alternative solutions proposed in the literature, when taking item wording into account. Construct validity was shown by substantial associations with related constructs, based on both self-reported (e.g., depressive symptoms and low social self-esteem), and peer-reported variables (e.g., victimization). Furthermore, a significant association was found between the CLS and a peer-reported measure of loneliness. Collectively, these findings provide a solid foundation for the continuing use of the CLS as a measure of childhood loneliness. PMID- 26354496 TI - Formosa haliotis sp. nov., a brown-alga-degrading bacterium isolated from the gut of the abalone Haliotis gigantea. AB - Four brown-alga-degrading, Gram-stain-negative, aerobic, non-flagellated, gliding and rod-shaped bacteria, designated LMG 28520T, LMG 28521, LMG 28522 and LMG 28523, were isolated from the gut of the abalone Haliotis gigantea obtained in Japan. The four isolates had identical random amplified polymorphic DNA patterns and grew optimally at 25 degrees C, at pH 6.0-9.0 and in the presence of 1.0-4.0 % (w/v) NaCl. Phylogenetic trees based on 16S rRNA gene sequences placed the isolates in the genus Formosa with Formosa algae and Formosa arctica as closest neighbours. LMG 28520T and LMG 28522 showed 100 % DNA-DNA relatedness to each other, 16-17 % towards F. algae LMG 28216T and 17-20 % towards F. arctica LMG 28318T; they could be differentiated phenotypically from these established species. The predominant fatty acids of isolates LMG 28520T and LMG 28522 were summed feature 3 (iso-C15 : 0 2-OH and/or C16 : 1omega7c), iso-C15 : 1 G and iso C15 : 0. Isolate LMG 28520T contained menaquinone-6 (MK-6) as the major respiratory quinone and phosphatidylethanolamine, two unknown aminolipids and an unknown lipid as the major polar lipids. The DNA G+C content was 34.4 mol% for LMG 28520T and 35.5 mol% for LMG 28522. On the basis of their phylogenetic and genetic distinctiveness, and differential phenotypic properties, the four isolates are considered to represent a novel species of the genus Formosa, for which the name Formosa haliotis sp. nov. is proposed. The type strain is LMG 28520T ( = NBRC 111189T). PMID- 26354497 TI - Helicity multiplexed broadband metasurface holograms. AB - Metasurfaces are engineered interfaces that contain a thin layer of plasmonic or dielectric nanostructures capable of manipulating light in a desirable manner. Advances in metasurfaces have led to various practical applications ranging from lensing to holography. Metasurface holograms that can be switched by the polarization state of incident light have been demonstrated for achieving polarization multiplexed functionalities. However, practical application of these devices has been limited by their capability for achieving high efficiency and high image quality. Here we experimentally demonstrate a helicity multiplexed metasurface hologram with high efficiency and good image fidelity over a broad range of frequencies. The metasurface hologram features the combination of two sets of hologram patterns operating with opposite incident helicities. Two symmetrically distributed off-axis images are interchangeable by controlling the helicity of the input light. The demonstrated helicity multiplexed metasurface hologram with its high performance opens avenues for future applications with functionality switchable optical devices. PMID- 26354498 TI - Fatal Erosion Atrial Septal Defect Device. AB - Percutaneus device closure of atrial septal defects offers an alternative to conventional surgical repair. While procedure techniques and devices have improved, severe complications remain that are neither completely understood nor entire predictable. We present a case of a 19-year-old female with left atrial erosion leading to lethal pericardial tamponade 1 month after ASD II closure using the Nit Occlude ASD-R(r) (NOASD-R, pfm Medical, Cologne, Germany). To our knowledge this is the first reported lethal complication related to this device. PMID- 26354499 TI - Justification and Indifference: Diverse Permissive Attitudes Toward Witnessed Violence Against the Elderly and Disabled. AB - The violence against the elderly and disabled is widespread. This means that many people who witness acts of violence against elders and the disabled do not react. Instead, they are rather inclined to develop permissive attitudes. The presented article distinguishes two permissive attitudes toward witnessed violence against the elderly and disabled: justification and indifference. The rationale for such differentiation is justified with reference to differences concerning (a) the strength of their relationship, (b) their frequency distribution in the population, and (c) the disparate influence of the underlying predictors. A survey study carried out on a nationwide representative sample of 1,000 adult Poles was the empirical basis for answering research questions. The study showed that domestic violence against elders and the disabled is a noticeable phenomenon in the population of Poland. Around 50% of respondents claimed that they came in touch with physical, economic, or psychological violence against the elderly. More than 30% reported the same in the case of disabled persons. Based on this study, it was found that justification of and indifference to violence were actually unrelated phenomena. Moreover, justification was much less widespread in the population than indifference. It seems easier to accept excuses for passivity in the face of violence than to find justifications for violence. Both permissive attitudes turned out to have a disparate pattern of predictors: Justification turned out to be mainly a function of environmental exposure to violence, whereas indifference was mainly a matter of worldview based on materialism and the imperative of self-interest. PMID- 26354500 TI - Ambivalent Sexism, Alcohol Use, and Intimate Partner Violence Perpetration. AB - Research on risk factors for men's perpetration of intimate partner violence (IPV) has shown a high correlation with problem alcohol use. Additional studies, however, indicate that the alcohol-IPV link is neither simple nor necessarily direct and that a range of factors may moderate this relationship. Using a national, community-based sample of 255 men, the present study examined the moderating effects of ambivalent sexism (i.e., hostile and benevolent sexism) on the relationship between alcohol use and IPV perpetration. The findings show that both greater alcohol consumption and high hostile sexism are positively associated with IPV perpetration, and that hostile sexism moderates the alcohol IPV relationship for perpetration of physical IPV, but not for psychological IPV. Moreover, high levels of alcohol consumption have a greater impact on physical IPV perpetration for men low in hostile sexism than for men high in hostile sexism, lending support to the multiple threshold model of the alcohol-IPV link. Implications of the findings for prevention, intervention, and future research are discussed. PMID- 26354501 TI - Myocardial shortening in 3 orthogonal directions and its transmural variation in patients with nonobstructive hypertrophic cardiomyopathy. AB - BACKGROUND: Although longitudinal strain (LS) is known to be reduced in patients with hypertrophic cardiomyopathy (HCM), it has not been elucidated whether or not circumferential strain (CS) is reduced. We aimed to determine whether multidirectional and layer-specific myocardial strain is reduced in patients with nonobstructive HCM. METHODS AND RESULTS: Speckle-tracking echocardiography was performed in 41 HCM patients and 27 control subjects. Segmental and global LS and CS were measured in the inner, mid, and outer layers. Global LS was significantly lower in the HCM group than in controls in the inner (-10.3+/-2.9 vs. -14.8+/ 2.0%, P<0.001), mid (-8.7+/-2.6 vs. -13.8+/-1.9%, P<0.001), and outer (-7.2+/-2.6 vs. -11.9+/-1.9%, P<0.001) layers. Global CS was preserved in the inner layer ( 23.8+/-4.7 vs. -24.3+/-3.3%, P=0.69) but reduced in the mid (-10.3+/-3.1 vs. 13.3+/-2.5%, P<0.001) and outer layers (-6.7+/-2.3 vs. -8.6+/-2.3%, P=0.002). Differences in CS between the inner and outer layers correlated with segmental relative wall thickness (r=-0.20, P=0.002). Furthermore, only the absolute value of global CS in the inner layer positively correlated with left ventricular ejection fraction (r=0.32, P<0.01) among these multidirectional and layer specific strains. CONCLUSIONS: In patients with HCM, not only the LS in all layers but also CS in the mid and outer layers was reduced, presumably reflecting impaired myocardial function. In contrast, CS in the inner layer was preserved, being associated with maintenance of chamber function. PMID- 26354502 TI - Cystatin C-based eGFR is a superior prognostic parameter to creatinine-based eGFR in post-endovascular therapy peripheral artery disease patients. AB - BACKGROUND: Kidney dysfunction is reportedly associated with adverse outcome in patients with peripheral artery disease (PAD). Estimated glomerular filtration rate (eGFR), a recently popularized index for assessing kidney function, is calculated using serum creatinine or cystatin C. Compared with creatinine-based eGFR (eGFRcr), cystatin C-based eGFR (eGFRcys) is less affected by age, gender, and muscle mass. We hypothesized that eGFRcys is a feasible prognostic biomarker despite muscle sarcopenia in patients with PAD. METHODS AND RESULTS: We calculated both eGFRcr and eGFRcys according to the Kidney Disease: Improving Global Outcomes (KDIGO) guideline in 234 PAD patients who underwent endovascular therapy. Patients were prospectively followed during a median follow-up period of 964 days for the endpoint of major adverse cardiovascular and cerebrovascular events (MACCE). On multivariate Cox proportional hazard analysis eGFRcys, but not eGFRcr, was an independent predictor of MACCE. The C index was larger for eGFRcys than eGFRcr (0.69 vs. 0.57, P=0.0006). On Kaplan-Meier analysis the incidence of MACCE was increased with advancing chronic kidney disease stage based on eGFRcys, but not on eGFRcr, in patients with PAD. Net reclassification index was improved with the addition of eGFRcys to basic predictors. CONCLUSIONS: Compared with eGFRcr, eGFRcys may be a more reliable biomarker for MACCE and patient risk stratification. PMID- 26354503 TI - What Is the Prognostic Morphology of Coronary Plaque in Patients With Chronic Kidney Disease? PMID- 26354504 TI - In vitro and in vivo evaluation of cucurbitacin E on rat hepatic CYP2C11 expression and activity using LC-MS/MS. AB - This study explored the effects of cucurbitacin E (CuE), a bioactive compound from Cucurbitaceae, on the metabolism/pharmacokinetic of tolbutamide, a model CYP2C9/11 probe substrate, and hepatic CYP2C11 expression in rats. Liquid chromatography-(tandem) mass spectrometry (LC-MS/MS) assay was used to detect tolbutamide as well as 4-hydroxytolbutamide, and then successfully applied to the pharmacokinetic study of tolbutamide in rats. The effect of CuE on CYP2C11 expression was determined by western blot. CuE (1.25-100 MUmol L-1) competitively inhibited tolbutamide 4-hydroxylation (CYP2C11) activity only in concentration dependent manner with a K i value of 55.5 MUmol L-1 in vitro. In whole animal studies, no significant difference in metabolism/pharmacokinetic of tolbutamide was found for the single pretreatment groups. In contrast, multiple pretreatments of CuE (200 MUg kg-1 d-1, 3 d, i.p.) significantly decreased tolbutamide clearance (CL) by 25% and prolonged plasma half-time (T 1/2) by 37%. Moreover, CuE treatment (50-200 MUg kg-1 d-1, i.p.) for 3 d did not affect CYP2C11 expression. These findings demonstrated that CuE competitively inhibited the metabolism of CYP2C11 substrates but had no effect on rat CYP2C11 expression. This study may provide a useful reference for the reasonable and safe use of herbal or natural products containing CuE to avoid unnecessary drug-drug interactions. PMID- 26354505 TI - Effects of temperature and cellular interactions on the mechanics and morphology of human cancer cells investigated by atomic force microscopy. AB - Cell mechanics plays an important role in cellular physiological activities. Recent studies have shown that cellular mechanical properties are novel biomarkers for indicating the cell states. In this article, temperature controllable atomic force microscopy (AFM) was applied to quantitatively investigate the effects of temperature and cellular interactions on the mechanics and morphology of human cancer cells. First, AFM indenting experiments were performed on six types of human cells to investigate the changes of cellular Young's modulus at different temperatures and the results showed that the mechanical responses to the changes of temperature were variable for different types of cancer cells. Second, AFM imaging experiments were performed to observe the morphological changes in living cells at different temperatures and the results showed the significant changes of cell morphology caused by the alterations of temperature. Finally, by co-culturing human cancer cells with human immune cells, the mechanical and morphological changes in cancer cells were investigated. The results showed that the co-culture of cancer cells and immune cells could cause the distinct mechanical changes in cancer cells, but no significant morphological differences were observed. The experimental results improved our understanding of the effects of temperature and cellular interactions on the mechanics and morphology of cancer cells. PMID- 26354506 TI - Kv1.3 channel blockade enhances the phagocytic function of RAW264.7 macrophages. AB - This study aimed to comprehend the largely unknown role of voltage-gated potassium channel 1.3 (Kv1.3) in the phagocytic function of macrophages. We found that blocking of the Kv1.3 channel with 100 pmol L(-1) Stichodactyla helianthus neurotoxin (ShK) enhanced the phagocytic capacities of both resting and lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages in the chicken erythrocyte system. In the fluorescein isothiocyanate (FITC)-labeled Escherichia coli k-12 system, ShK increased the phagocytic capacities of resting RAW264.7 cells, but not of the LPS-stimulated cells, as LPS alone stimulated almost saturated phagocytosis of the macrophages. ShK increased the nitric oxide (NO) production in LPS-activated cells, but not in resting RAW264.7 cells. There was no effect of ShK alone on the cytokine secretions in resting RAW264.7 cells, but it suppressed IL-1beta secretion in LPS-stimulated RAW264.7 cells. At a concentration of 100 pmol L(-1), ShK did not affect the viability of the tested cells. Kv1.3 was expressed in RAW264.7 cells; this expression was downregulated by LPS, but significantly upregulated by disrupting caveolin-dependent endocytosis with filipin III. In addition, cytochalasin D, an inhibitor of actin polymerization, did not affect the Kv1.3 expression. Thus, blocking of the Kv1.3 channel enhances the phagocytic capacity and NO production of this cell line. Our results suggest that Kv1.3 channel serves as a negative regulator of phagocytosis in macrophages and can therefore be a potential target in the treatment of macrophage dysfunction. PMID- 26354507 TI - The Hybrid Approach for Intervention of Chronic Total Occlusions. AB - The "hybrid" approach to chronic total occlusion (CTO) percutaneous coronary intervention (PCI) was developed to provide guidance on optimal crossing strategy selection. Dual angiography remains the cornerstone of clinical decision making in CTO PCI. Four angiographic parameters are assessed: (a) morphology of the proximal cap (clear-cut or ambiguous); (b) occlusion length; (c) distal vessel size and presence of bifurcations beyond the distal cap; and (d) location and suitability of location and suitability of a retrograde conduit (collateral channels or bypass grafts) for retrograde access. Antegrade wire escalation is favored for short (<20 mm) occlusions, usually escalating rapidly from a soft tapered-tip polymer-jacketed guidewire to a stiff polymer-jacketed or tapered-tip guidewire. Antegrade dissection/re-entry is favored in long (>=20 mm long) occlusions, trying to minimize the dissection length by re-entering into the distal true lumen immediately after the occlusion. Primary retrograde approach is preferred for lesions with an ambiguous proximal cap, poor distal target, good interventional collaterals, and heavy calcification,as well as chronic kidney disease. The "hybrid" approach advocates early change between strategies to enable CTO crossing in the most efficacious, efficient, and safe way. Several early studies are demonstrating high success and low complication rates with use of the "hybrid" approach, supporting its expanding use in CTO PCI. PMID- 26354508 TI - Collateral Circulation in Chronic Total Occlusions - an interventional perspective. AB - Human coronary collaterals are inter-coronary communications that are believed to be present from birth. In the presence of chronic total occlusions, recruitment of flow via these collateral anastomoses to the arterial segment distal to occlusion provide an alternative source of blood flow to the myocardial segment at risk. This mitigates the ischemic injury. Clinical outcome of coronary occlusion ie. severity of myocardial infarction/ischemia, impairment of cardiac function and possibly survival depends not only on the acuity of the occlusion, extent of jeopardized myocardium, duration of ischemia but also to the adequacy of collateral circulation. Adequacy of collateral circulation can be assessed by various methods. These coronary collateral channels have been used successfully as a retrograde access route for percutaneous recanalization of chronic total occlusions. Factors that promote angiogenesis and further collateral remodeling ie. arteriogenesis have been identified. Promotion of collateral growth as a therapeutic target in patients with no suitable revascularization option is an exciting proposal. PMID- 26354509 TI - Radiation Safety During Interventions of Coronary Chronic Total Occlusion. AB - During percutaneous coronary interventions (PCI) for chronic total occlusion (CTO), prolonged procedures increase the risk of excessive radiation exposure. These situations harbor a major concern to protect patients and personnel in the cardiac interventional laboratory (CCL). Important questions regarding radiation safety for interventional cardiologists performing PCI for CTO lesions are discussed and concrete applications are suggested. PMID- 26354510 TI - Applied Pathology for Interventions of Coronary Chronic Total Occlusion. AB - Percutaneous coronary intervention of chronically occluded vessels can result in significant improvement in symptoms, relieve myocardial ischemia, and affect a reduction in major adverse cardiac events. Likelihood of achieving successful revascularization can be significantly enhanced with a thorough understanding of the pathology of these occluded coronary arteries. In this chapter, various steps and techniques to cross the CTO lesion and recanalize it are discussed in details. PMID- 26354511 TI - Training Standards and Recommendations for Intervention on Chronic Total Occlusions. AB - Despite major advances in coronary intervention, the recanalization of a chronic total occlusion (CTO) remains a challenge for many interventional cardiologists. Complex anatomy and lesion characteristics demand a special set of skills for procedural success. Provided patient selection is appropriate, CTO intervention can confer a variety of benefits including relief of angina, improvement in left ventricular function and reduction in ischemic burden. The chances of procedural success are enhanced by having a dedicated CTO program. This involves adequate training of staff, quality control and availability of equipment. A diverse toolkit allows variation in strategy and increases procedural success. Further, skills and equipment are required to manage complications like vessel dissection, perforation and the resultant ischemic or mechanical complications. These procedures can often be lengthy and giving careful consideration to peri procedural issues like radiation exposure and contrast dose plays a vital role in ensuring optimal patient outcomes and radiation hygiene. In this article we review the evidence behind indications for CTO intervention and discuss the development of a CTO program. PMID- 26354512 TI - Antegrade Techniques for Chronic Total Occlusions. AB - By convention, a total obstruction of the coronary artery with no flow at the occluded segment that has been present for at least 3 months is termed as chronic total occlusion or CTO. This is to be distinguished from a sudden occlusion of the coronary artery lumen by a thrombus during an acute myocardial infarction. Percutaneous coronary intervention (PCI) of CTO is increasingly being performed by interventional cardiologists with improved success rates. In this article, the focus will be on antegrade techniques that will assist the operator to maximise the success rates and to minimise the complications. PMID- 26354513 TI - Retrograde Coronary Chronic Total Occlusion Intervention. AB - Coronary chronic total occlusion (CTO) is a frequent finding in patients with coronary artery disease. It remains one of the most challenging subsets, accounting for 10-20% of all percutaneous coronary interventions (PCI). Although remarkable progress in PCI has been made, it is reasonable to state that successful recanalization of CTO represents the "last frontier" of PCI. PCI of CTOs has been limited historically by technical success rates of 50-70%. The introduction of enhanced guidewires, microcatheter, channel dilatator with increasing operator experience, and innovative techniques such as the retrograde approach have raised hopes for better outcomes. This article goes into depth into various strategies of retrograde approach in CTO. PMID- 26354514 TI - Intravascular Ultrasound Guided Percutaneous Coronary Intervention for Chronic Total Occlusion. AB - Chronic total occlusion (CTO), a fascinating and dynamic niche in the realm of coronary artery disease, represents a major technical challenge for interventional cardiologists despite evolution of better guidewires, devices, experience and techniques. Effective wiring technique is the corner stone to success of percutaneous coronary intervention (PCI) in CTO. As a guide for guidewire crossing in CTO, coronary angiography is limited. On the other hand, intravascular ultrasound (IVUS) enhances the ability to identify coronary anatomy, the exact location of the guidewires within an artery, discriminating a true lumen from the false lumen before guidewire crossing. Some angiographic features have been suggested to be predictive of procedural failure, including blunt stump with a side branch at the site of occlusion. Novel use of IVUS can recognize the optimal entry point and evaluate if a guidewire properly penetrates the proximal cap of CTO. PMID- 26354515 TI - COMPLICATIONS OF RECANALIZATION OF CHRONIC TOTAL OCCLUSION. AB - Percutaneous Coronary Intervention (PCI) of Chronic Total Occlusions (CTO) is an accepted revascularization procedure. These complex procedures carry with them certain risks and potential complications. Complications of PCI such as contrast induced renal dysfunction, radiation, etc, assume more relevance given the length and complexity of these procedures. Further, certain complications such as donor vessel injury, foreign body entrapment are unique to CTO PCI. A thorough understanding of the potential complications is important in mitigating risk during these complex procedures. PMID- 26354516 TI - Role of CT Coronary Angiography in Recanalization of Chronic Total Occlusion. AB - Chronic total occlusion (CTO) is considered as the most challenging frontier in interventional cardiology and the last one to be conquered. With availability of state of art hardware, wires and catheters in particular and increased skills of the operators, the success rate for recanalization of CTO by percutaneous catheter intervention (PCI) has improved. Yet the complications rate and long term adverse events are high, mostly due to failure in tracking or navigation of hardware through the occluded CTO segment, prolonged exposure to radiation and high doses of contrast used. Therefore proper selection of patient is of utmost importance. One of the major challenges for successful CTO recanalization is satisfactory visualization of the occluded CTO segment. Conventional invasive catheterization fails to fill the gap and the shortcomings and handicaps of such invasive imaging can be resolved with the use of non-invasive CT coronary angiography (CTCA). CTCA helps to better define the morphological features of the occluded CTO segment, which are established predictors of success, like the actual length of the occluded segment and any calcification or tortuosity in its course. Integration of reconstructed three-dimensional CT coronary images with two-dimensional fluoroscopic images, offers directional guide to select the best angiographic plane for visualization of angiographically "missing segment". With advances in CT technology, CTCA has now become an established technology for pre procedure evaluation of CTO segment, thereby help in planning and execution of successful PCI. PMID- 26354517 TI - Bilateral compared with unilateral sacral nerve stimulation for faecal incontinence: results of a randomized, single-blinded crossover study. AB - AIM: This randomized single-blinded crossover study aimed to investigate whether bilateral sacral nerve stimulation (SNS) is more efficient than unilateral stimulation for faecal incontinence (FI). METHOD: Patients with FI who responded during a unilateral test stimulation, with a minimum improvement of 50% were eligible. Twenty-seven patients who were accepted to enter the trial were bilaterally implanted with two permanent leads and pacemakers. Patients were randomized into three periods of 4 weeks' stimulation including unilateral right, unilateral left and bilateral stimulation. Symptoms scores and bowel habit diaries were collected at baseline and in each study period. A 1-week washout was introduced between each study period. RESULTS: Twenty-seven (25 female) patients with a median age of 63 (36-84) years were bilaterally implanted from May 2009 to June 2012. The median number of episodes of FI per 3 weeks significantly decreased from 17 (3-54) at baseline to 2 (0-20) during stimulation on the right side, 2 (0-42) during stimulation on the left side and 1 (0-25) during bilateral stimulation. The Wexner incontinence score improved significantly from a median of 16 (10-20) at baseline to 9 (0-14) with right-side stimulation, 10 (0-15) with left-side stimulation and 9 (0-14) with bilateral stimulation. The differences between unilateral right or unilateral left and bilateral stimulation were non significant, for FI episodes (P = 0.3) or for Wexner incontinence score (P = 0.9). CONCLUSION: Bilateral SNS therapy for FI is not superior to standard unilateral stimulation in the short term. Equal functional results can be obtained regardless of the side of implantation. PMID- 26354518 TI - Engagement in the HIV Care Continuum among Key Populations in Tijuana, Mexico. AB - In Tijuana, Mexico, HIV is concentrated in sub-epidemics of key populations: persons who inject drugs (PWID), sex workers (SW), and men who have sex with men (MSM). To date, data on engagement in the HIV care continuum among these key populations, particularly in resource-constrained settings, are sparse. We pooled available epidemiological data from six studies (N = 3368) to examine HIV testing and treatment uptake in these key populations; finding an overall HIV prevalence of 5.7 %. Of the 191 identified HIV-positive persons, only 11.5 % knew their HIV positive status and 3.7 % were on ART. Observed differences between these HIV positive key populations suggest PWID (vs. non-PWID) were least likely to have previously tested or initiate HIV care. MSM (vs. non-MSM) were more likely to have previously tested but not more likely to know their HIV-positive status. Of persons aware of their HIV-positive status, SW (vs. non-SW) were more likely to initiate HIV care. Findings suggest engagement of key populations in HIV treatment is far below estimates observed for similarly resource-constrained generalized epidemics in sub-Saharan Africa. These data provide one of the first empirical-snapshots highlighting the extent of HIV treatment disparities in key populations. PMID- 26354519 TI - Relationship Factors and Condom Use Among Women with a History of Intimate Partner Violence. AB - Women who experience intimate partner violence (IPV) are at increased risk for HIV infection. To further the understanding of the dyadic factors that impact condom use among women, we investigated the impact of three relationship factors (i.e., power, fear, and dependence) on the association between HIV-related information, motivation, and behavioral skills [constructs from the information motivation-behavioral skills (IMB) model] and condom use among abused women. Data from 133 urban, low-income women recruited from several community-based agencies (e.g., domestic violence agencies, women's health organizations, hospitals, Department of Health and Human Services, and Family Court) showed that these women experienced high levels of IPV and that relationship power, fear of abuse, and partner dependence were all associated with condom use. Multivariable models revealed that fear of abuse and partner dependence moderated the association between IMB constructs and condom use but relationship power did not. Results highlight the critical need to incorporate strategies to address relationship factors in HIV prevention programs with abused women. PMID- 26354520 TI - Research participants' perceptions and views on consent for biobank research: a review of empirical data and ethical analysis. AB - BACKGROUND: Appropriate information and consent has been one of the most intensely discussed topics within the context of biobank research. In parallel to the normative debate, many socio-empirical studies have been conducted to gather experiences, preferences and views of patients, healthy research participants and further stakeholders. However, there is scarcity of literature which connects the normative debate about justifications for different consent models with findings gained in empirical research. In this paper we discuss findings of a limited review of socio-empirical research on patients' and healthy research participants' experiences and views regarding consent to biobank research in light of ethical principles for appropriate information and consent. METHODS: Review question: Which empirical data are available on research participants' perceptions and views regarding information and elicitation of consent for biobank research? Search of articles published till March 1st 2014 in Pubmed. Review of abstracts and potentially relevant full text articles by two authors independently. As categories for content analysis we defined (i) understanding or recall of information, (ii) preferences regarding information or consent, and (iii) research participants' concerns. RESULTS: The search in Pubmed yielded 337 abstracts of which 10 articles were included in this study. Approaches to information and consent varied considerably across the selected studies. The majority of research participants opted for some version of limited consent when being informed about such possibility. Among the factors influencing the type of preferred consent were information about sponsoring of biobank research by pharmaceutical industry and participants' trade-off between privacy and perceived utility. Studies investigating research participants' understanding and recall regarding the consent procedure indicated considerable lack of both aspects. Research participants' perceptions of benefits and harms differ across those studies. CONCLUSION: The knowledge, perceptions and views of research participants who have undergone a consent procedure within the context of biobank research raise several questions on the issue of how to inform and elicit consent in an ethically acceptable way. In our empirical-ethical analysis we develop suggestions on how the practice of eliciting consent in the biobank context should be improved. PMID- 26354521 TI - Comparison of efficacy and safety of first-line palliative chemotherapy with EOX and mDCF regimens in patients with locally advanced inoperable or metastatic HER2 negative gastric or gastroesophageal junction adenocarcinoma: a randomized phase 3 trial. AB - The aim of the study was to compare efficacy and safety of first-line palliative chemotherapy with (EOX) epirubicin/oxaliplatin/capecitabine and (mDCF) docetaxel/cisplatin/5FU/leucovorin regimens for untreated advanced HER2-negative gastric or gastroesophageal junction adenocarcinoma. Fifty-six patients were randomly assigned to mDCF (docetaxel 40 mg/m(2) day 1, leucovorin 400 mg/m(2) day 1, 5FU 400 mg/m(2) bolus day 1, 5FU 1000 mg/m(2)/d days 1 and 2, cisplatin 40 mg/m(2) day 3) or EOX (epirubicin 50 mg/m(2) day 1, oxaliplatin 130 mg/m(2) day 1, capecitabine 1250 mg/m(2)/d days 1-21). The primary endpoint was overall survival. The median overall survival was 9.5 months with EOX and 11.9 months with mDCF (p = 0.135), while median progression-free survival was 6.4 and 6.8 months, respectively (p = 0.440). Two-year survival rate was 22.2 % with mDCF compared to 5.2 % with EOX. Patients in the EOX arm had more frequent reductions in chemotherapy doses (34.5 vs. 3.7 %; p = 0.010) and delays in subsequent chemotherapy cycles (82.8 vs. 63.0 %; p = 0.171). There was no statistically significant difference in the rates of grade 3-4 adverse events (EOX 79.3 vs. mDCF 61.5 %; p = 0.234). As compared with the mDCF, the EOX regimen was associated with more frequent nausea (34.5 vs. 15.4 %), thromboembolic events (13.8 vs. 7.7 %), abdominal pain (13.8 vs. 7.7 %) and grades 3-4 neutropenia (72.4 vs. 50.0 %), but lower incidences of anemia (44.8 vs. 61.5 %), mucositis (6.9 vs. 15.4 %) and peripheral neuropathy (6.9 vs. 15.4 %). In conclusion, the mDCF regimen was associated with a statistically nonsignificant 2.4-month longer median overall survival without an increase in toxicity. This trial is registered at ClinicalTrials.gov, number NCT02445209. PMID- 26354522 TI - Development of chloroplast genomic resources for Cynara. AB - In this study, new chloroplast (cp) resources were developed for the genus Cynara, using whole cp genomes from 20 genotypes, by means of high-throughput sequencing technologies. Our target species included seven globe artichokes, two cultivated cardoons, eight wild artichokes, and three other wild Cynara species (C. baetica, C. cornigera and C. syriaca). One complete cp genome was isolated using short reads from a whole-genome sequencing project, while the others were obtained by means of long-range PCR, for which primer pairs are provided here. A de novo assembly strategy combined with a reference-based assembly allowed us to reconstruct each cp genome. Comparative analyses among the newly sequenced genotypes and two additional Cynara cp genomes ('Brindisino' artichoke and C. humilis) retrieved from public databases revealed 126 parsimony informative characters and 258 singletons in Cynara, for a total of 384 variable characters. Thirty-nine SSR loci and 34 other INDEL events were detected. After data analysis, 37 primer pairs for SSR amplification were designed, and these molecular markers were subsequently validated in our Cynara genotypes. Phylogenetic analysis based on all cp variable characters provided the best resolution when compared to what was observed using only parsimony informative characters, or only short 'variable' cp regions. The evaluation of the molecular resources obtained from this study led us to support the 'super-barcode' theory and consider the total cp sequence of Cynara as a reliable and valuable molecular marker for exploring species diversity and examining variation below the species level. PMID- 26354523 TI - Endometrial cancer. AB - Endometrial cancer is the most common gynaecological tumour in developed countries, and its incidence is increasing. The most frequently occurring histological subtype is endometrioid adenocarcinoma. Patients are often diagnosed when the disease is still confined to the uterus. Standard treatment consists of primary hysterectomy and bilateral salpingo-oophorectomy, often using minimally invasive approaches (laparoscopic or robotic). Lymph node surgical strategy is contingent on histological factors (subtype, tumour grade, involvement of lymphovascular space), disease stage (including myometrial invasion), patients' characteristics (age and comorbidities), and national and international guidelines. Adjuvant treatment is tailored according to histology and stage. Various classifications are used to assess the risks of recurrence and to determine optimum postoperative management. 5 year overall survival ranges from 74% to 91% in patients without metastatic disease. Trials are ongoing in patients at high risk of recurrence (including chemotherapy, chemoradiation therapy, and molecular targeted therapies) to assess the modalities that best balance optimisation of survival with the lowest adverse effects on quality of life. PMID- 26354524 TI - The Mosaic Ancestry of the Drosophila Genetic Reference Panel and the D. melanogaster Reference Genome Reveals a Network of Epistatic Fitness Interactions. AB - North American populations of Drosophila melanogaster derive from both European and African source populations, but despite their importance for genetic research, patterns of ancestry along their genomes are largely undocumented. Here, I infer geographic ancestry along genomes of the Drosophila Genetic Reference Panel (DGRP) and the D. melanogaster reference genome, which may have implications for reference alignment, association mapping, and population genomic studies in Drosophila. Overall, the proportion of African ancestry was estimated to be 20% for the DGRP and 9% for the reference genome. Combining my estimate of admixture timing with historical records, I provide the first estimate of natural generation time for this species (approximately 15 generations per year). Ancestry levels were found to vary strikingly across the genome, with less African introgression on the X chromosome, in regions of high recombination, and at genes involved in specific processes (e.g., circadian rhythm). An important role for natural selection during the admixture process was further supported by evidence that many unlinked pairs of loci showed a deficiency of Africa-Europe allele combinations between them. Numerous epistatic fitness interactions may therefore exist between African and European genotypes, leading to ongoing selection against incompatible variants. By focusing on hubs in this network of fitness interactions, I identified a set of interacting loci that include genes with roles in sensation and neuropeptide/hormone reception. These findings suggest that admixed D. melanogaster samples could become an important study system for the genetics of early-stage isolation between populations. PMID- 26354525 TI - Optimising gut colonisation resistance against Clostridium difficile infection. AB - Clostridium difficile is the dominant cause of pseudomembranous colitis in nosocomial environments. C. difficile infection (CDI) generally affects elderly (>=65 years of age) hospital inpatients who have received broad-spectrum antimicrobial treatment. CDI has a 30 % risk of re-infection and a subsequent 60 % risk of relapse thereafter, leading to a high economic burden of over 7 billion pounds sterling and over 900,000 cases in the USA and Europe per annum. With the long-term consequences of faecal transplantation currently unknown, and limited spectrum of effective antibiotics, there is an urgent requirement for alternative means of preventing and treating CDI in high-risk individuals. Metagenomics has recently improved our understanding of the colonisation resistance barrier and how this could be optimised. pH, oxidation-reduction potentials and short-chain fatty acids have been suggested to inhibit C. difficile growth and toxin production in in vitro and in vivo studies. This review aims to pull together the evidence in support of a colonisation resistance barrier against CDI. PMID- 26354526 TI - The Metastatic Spine Disease Multidisciplinary Working Group Algorithms. AB - The Metastatic Spine Disease Multidisciplinary Working Group consists of medical and radiation oncologists, surgeons, and interventional radiologists from multiple comprehensive cancer centers who have developed evidence- and expert opinion-based algorithms for managing metastatic spine disease. The purpose of these algorithms is to facilitate interdisciplinary referrals by providing physicians with straightforward recommendations regarding the use of available treatment options, including emerging modalities such as stereotactic body radiation therapy and percutaneous tumor ablation. This consensus document details the evidence supporting the Working Group algorithms and includes illustrative cases to demonstrate how the algorithms may be applied. PMID- 26354528 TI - Novel hemagglutinating, hemolytic and cytotoxic activities of the intermediate subunit of Entamoeba histolytica lectin. AB - Galactose and N-acetyl-D-galactosamine (Gal/GalNAc) inhibitable lectin of Entamoeba histolytica, a common protozoan parasite, has roles in pathogenicity and induction of protective immunity in mouse models of amoebiasis. The lectin consists of heavy (Hgl), light (Lgl), and intermediate (Igl) subunits. Hgl has lectin activity and Lgl does not, but little is known about the activity of Igl. In this study, we assessed various regions of Igl for hemagglutinating activity using recombinant proteins expressed in Escherichia coli. We identified a weak hemagglutinating activity of the protein. Furthermore, we found novel hemolytic and cytotoxic activities of the lectin, which resided in the carboxy-terminal region of the protein. Antibodies against Igl inhibited the hemolytic activity of Entamoeba histolytica trophozoites. This is the first report showing hemagglutinating, hemolytic and cytotoxic activities of an amoebic molecule, Igl. PMID- 26354529 TI - Association between serum folate and vitamin B-12 and outcomes of assisted reproductive technologies. AB - BACKGROUND: Preconceptional folate and vitamin B-12 have been linked to beneficial reproductive outcomes in both natural pregnancies and those after assisted reproductive technology (ART) treatment. OBJECTIVE: The objective of the study was to evaluate the associations of serum folate and vitamin B-12 with ART outcomes. DESIGN: This analysis included a random sample of 100 women (154 ART cycles) participating in a prospective cohort study [Environment and Reproductive Health (EARTH)] at the Massachusetts General Hospital Fertility Center (2007 2013). Serum folate and vitamin B-12 were measured in blood samples collected between days 3 and 9 of treatment. Generalized estimating equations with adjustment for age, BMI, and race were used to evaluate the association of serum folate and vitamin B-12 with ART outcomes. RESULTS: Women in the highest quartile of serum folate (>26.3 ng/mL) had 1.62 (95% CI: 0.99, 2.65) times the probability of live birth compared with women in the lowest quartile (<16.6 ng/mL). Women in the highest quartile of serum vitamin B-12 (>701 pg/mL) had 2.04 (95% CI: 1.14, 3.62) times the probability of live birth compared with women in the lowest quartile (<439 pg/mL). Suggestive evidence of an interaction was observed; women with serum folate and vitamin B-12 concentrations greater than the median had 1.92 (95% CI: 1.12, 3.29) times the probability of live birth compared with women with folate and vitamin B-12 concentrations less than or equal to the median. This translated into an adjusted difference in live birth rates of 26% (95% CI: 10%, 48%; P = 0.02). CONCLUSION: Higher serum concentrations of folate and vitamin B-12 before ART treatment were associated with higher live birth rates among a population exposed to folic acid fortification. This trial was registered at clinicaltrials.gov as NCT00011713. PMID- 26354527 TI - Afatinib in Non-Small Cell Lung Cancer Harboring Uncommon EGFR Mutations Pretreated With Reversible EGFR Inhibitors. AB - BACKGROUND: Afatinib, an irreversible ErbB family blocker, is approved for treatment of patients with previously untreated non-small cell lung cancer (NSCLC) harboring activating epidermal growth factor receptor (EGFR) mutations. Efficacy of afatinib in EGFR tyrosine kinase inhibitor-naive (TKI-naive) patients with uncommon EGFR mutations (other than exon 19 deletions or exon 21 point mutations) has been reported; however, efficacy in TKI-pretreated patients with uncommon EGFR mutations is unknown. MATERIALS AND METHODS: In the afatinib compassionate use program (CUP), patients with advanced or metastatic, histologically confirmed NSCLC progressing after at least one line of chemotherapy and one line of EGFR-TKI treatment were enrolled. Demographic data, mutation type, response rates, time to treatment failure (TTF), and safety in patients harboring uncommon EGFR mutations were reported. RESULTS: In 60 patients (63% female, median age 63 years [range: 30-84 years]), a total of 66 uncommon EGFR mutations including 30 T790M mutations were reported (18.4% and 11%, respectively, of known EGFR mutations within the CUP). Most patients (67%) received afatinib as third- or fourth-line treatment. Median TTF was 3.8 months (range: 0.2 to >24.6 months; p = .244) in patients with uncommon mutations compared with 5.1 months (range: 0.1 to >21.1 months) in patients with common mutations (n = 165). Pronounced activity was observed with E709X mutations (TTF >12 months). No new safety signals were detected. CONCLUSION: Afatinib is clinically active and well tolerated in many TKI-pretreated NSCLC patients harboring uncommon EGFR mutations. Compared with results reported in TKI-naive patients, activity was also indicated in patients with T790M and exon 20 insertion mutations. PMID- 26354531 TI - Efficacy of fish intake on vitamin D status: a meta-analysis of randomized controlled trials. AB - BACKGROUND: It is well known that fish is the major natural source of vitamin D in the diet; therefore, this meta-analysis investigated the influence of fish consumption in randomized controlled trials (RCTs) on serum 25-hydroxyvitamin D [25(OH)D] concentrations. OBJECTIVE: A literature search was carried out in Medline, Embase, Web of Science, and the Cochrane Library (up to February 2014) for RCTs that investigated the effect of fish consumption on 25(OH)D concentrations in comparison to other dietary interventions. RESULTS: Seven articles and 2 unpublished study data sets with 640 subjects and 14 study groups met the inclusion criteria and were included in this meta-analysis. Compared with controls, the consumption of fish increased 25(OH)D concentrations, on average, by 4.4 nmol/L (95% CI: 1.7, 7.1 nmol/L; P < 0.0001, I(2) = 25%; 9 studies).The type of the fish also played a key role: the consumption of fatty fish resulted in a mean difference of 6.8 nmol/L (95% CI: 3.7, 9.9 nmol/L; P < 0.0001, I(2) = 0%; 7 study groups), whereas for lean fish the mean difference was 1.9 nmol/L (95% CI: -2.3, 6.0 nmol/L; P < 0.38, I(2) = 37%; 7 study groups). Short-term studies (4-8 wk) showed a mean difference of 3.8 nmol/L (95% CI: 0.6, 6.9 nmol/L; P < 0.02, I(2) = 38%; 10 study groups), whereas in long-term studies (~6 mo) the mean difference was 8.3 nmol/L (95% CI: 2.1, 14.5 nmol/L; P < 0.009, I(2) = 0%; 4 study groups). CONCLUSION: As the major food source of vitamin D, fish consumption increases concentrations of 25(OH)D, although recommended fish intakes cannot optimize vitamin D status. PMID- 26354530 TI - Dietary inflammatory index and telomere length in subjects with a high cardiovascular disease risk from the PREDIMED-NAVARRA study: cross-sectional and longitudinal analyses over 5 y. AB - BACKGROUND: Dietary factors can affect telomere length (TL), a biomarker of aging, through oxidation and inflammation-related mechanisms. A Dietary Inflammatory Index (DII) could help to understand the effect of the inflammatory potential of the diet on telomere shortening. OBJECTIVE: This study aimed to determine the association of the DII with TL and to examine whether diet associated inflammation could modify the telomere attrition rate after a 5-y follow-up of a Mediterranean dietary intervention. DESIGN: This was a prospective study of 520 participants at high cardiovascular disease risk (mean +/- SD age: 67.0 +/- 6.0 y, 45% males) from the PREDIMED-NAVARRA (PREvencion con DIeta MEDiterranea-NAVARRA) trial. Leukocyte TL was measured by quantitative real-time polymerase chain reaction at baseline and after 5 y of follow-up. The DII was calculated from self-reported data by using a validated 137-item food-frequency questionnaire. RESULTS: Longer telomeres at baseline were found in participants who had a more anti-inflammatory diet (lowest DII score) (P-trend = 0.012). Longitudinal analyses further showed that a greater anti-inflammatory potential of the diet (i.e., a decrease in the DII) could significantly slow down the rate of telomere shortening. Moreover, the multivariable-adjusted OR for short telomeres (z score <=20th percentile) was 1.80 (95% CI: 1.03, 3.17) in a comparison between the highest (proinflammatory) and the lowest (anti inflammatory) DII tertiles. Similarly, a greater DII (greatest proinflammatory values) after a 5-y follow-up was associated with almost a 2-fold higher risk of accelerated telomere attrition compared with the highest decrease in DII (greatest anti-inflammatory values) during this period (P-trend = 0.025). CONCLUSIONS: This study showed both cross-sectional and longitudinal associations between the inflammatory potential of the diet and telomere shortening in subjects with a high cardiovascular disease risk. Our findings are consistent with, but do not show, a beneficial effect of adherence to an anti-inflammatory diet on aging and health by slowing down telomere shortening. These results suggest that diet might play a key role as a determinant of TL through proinflammatory or anti-inflammatory mechanisms. This trial was registered at controlled-trials.com as ISRCTN35739639. PMID- 26354532 TI - Interaction between current vitamin D supplementation and menopausal hormone therapy use on breast cancer risk: evidence from the E3N cohort. AB - BACKGROUND: Experimental studies suggest protective effects of vitamin D on breast carcinogenesis, particularly on estrogen receptor-positive tumors. Epidemiologic data are less conclusive. OBJECTIVE: Our objective was to investigate the association between postmenopausal breast cancer risk and current or past vitamin D supplementation overall and according to the use of menopausal hormone therapy (MHT). DESIGN: Between 1995 and 2008, 2482 invasive breast cancer cases were diagnosed among 57,403 postmenopausal women from the E3N prospective cohort during 581,085 person-years. Vitamin D supplementation was assessed from biennially self-administered questionnaires sent in 1995, 2000, 2002, and 2005 and from medico-administrative data on drug reimbursements since 2004. Multivariable HRs for primary invasive breast cancer and 95% CIs were estimated by using Cox models. RESULTS: A decreased postmenopausal breast cancer risk was associated with current (HR: 0.82; 95% CI: 0.69, 0.97) but not past (HR: 1.10; 95% CI: 0.92, 1.31) vitamin D supplementation (P-homogeneity = 0.02). The association with current vitamin D supplementation differed according to MHT use: ever users (HR: 0.74; 95% CI: 0.60, 0.90) and never users (HR: 1.13; 95% CI: 0.89, 1.56); P-homogeneity = 0.02. CONCLUSIONS: In this observational study, current vitamin D supplementation, mostly taken daily and combined with calcium, was associated with a decreased postmenopausal breast cancer risk in MHT users. These findings should be confirmed before considering vitamin D supplementation to partly balance the MHT-associated increased breast cancer risk. PMID- 26354533 TI - Maternal dietary patterns during pregnancy and body composition of the child at age 6 y: the Generation R Study. AB - BACKGROUND: Maternal diet during pregnancy may affect body composition of the offspring later in life, but evidence is still scarce. OBJECTIVE: We aimed to examine whether maternal dietary patterns during pregnancy are associated with body composition of the child at age 6 y. METHODS: This study was performed among 2695 Dutch mother-child pairs from a population-based prospective cohort study from fetal life onward. Maternal diet was assessed in early pregnancy by a 293 item semiquantitative food-frequency questionnaire. Vegetable, fish, and oil; nuts, soy, and high-fiber cereals; and margarine, snacks, and sugar dietary patterns were derived from principal component analysis. We measured weight and height of the child at age 6 y at the research center. Total body fat and regional fat mass percentages of the child were assessed with dual-energy X-ray absorptiometry. RESULTS: In the crude models, statistically significant associations were found for higher adherence to the vegetable, fish, and oil dietary pattern and the nuts, soy, and high-fiber cereals dietary pattern with lower body mass index, lower fat mass index, and lower risk of being overweight, but none of these associations remained significant after adjustment for sociodemographic and lifestyle factors. We found no associations between the margarine, snacks, and sugar dietary pattern and any of the outcomes. CONCLUSION: Our results suggest that the associations between maternal dietary patterns during pregnancy and body composition of the child at age 6 y are to a large extent explained by sociodemographic and lifestyle factors of mother and child. PMID- 26354534 TI - Examination of central body fat deposition as a risk factor for loss-of-control eating. AB - BACKGROUND: Elevated body mass index (BMI), higher waist-to-hip ratio, and body dissatisfaction have been investigated as risk factors for the development of bulimic symptoms. Central fat deposition may be particularly relevant to eating disorders. To our knowledge, the longitudinal relations between fat distribution, body dissatisfaction, and loss-of-control (LOC) eating development and maintenance have not been studied. OBJECTIVE: We examined body fat distribution, independent of BMI and depressive symptoms, as a unique correlate and predictor of body dissatisfaction and LOC eating cross-sectionally and over a 2-y follow up. DESIGN: Body composition was measured by using dual-energy X-ray absorptiometry in 294 adult women at risk of weight gain at baseline, 6 mo, and 24 mo. We assessed LOC eating, body dissatisfaction, and depressive symptoms at baseline, 6 wk, 6 mo, 12 mo, and 24 mo by using the Eating Disorder Diagnostic Interview, the Multidimensional Body-Self Relations Questionnaire-Appearance Scales Body Areas Satisfaction subscale, and the Center for Epidemiologic Studies Depression Scale, respectively. RESULTS: Independent of BMI, baseline total percentage body fat, percentage trunk fat, and percentage abdominal fat were related to greater body dissatisfaction. Total percentage body fat and trunk fat tended to be associated with greater body dissatisfaction at all subsequent time points. Women with a greater percentage trunk fat, specifically abdominal fat, were at highest risk of developing LOC eating. In the full sample, women with higher baseline percentage trunk and abdominal fat showed increases in LOC eating episode frequency over time, whereas LOC eating frequency remained stable among women with smaller percentages of fat in trunk and abdominal regions. CONCLUSION: These findings lend further support to the premise that increased central body fat deposition is associated with body image dissatisfaction and suggest that it may represent a risk and maintenance factor for LOC eating. This trial was registered at clinicaltrials.gov as NCT00456131. PMID- 26354535 TI - Short-term variability in body weight predicts long-term weight gain. AB - BACKGROUND: Body weight in lower animals and humans is highly stable despite a very large flux in energy intake and expenditure over time. Conversely, the existence of higher-than-average variability in weight may indicate a disruption in the mechanisms responsible for homeostatic weight regulation. OBJECTIVE: In a sample chosen for weight-gain proneness, we evaluated whether weight variability over a 6-mo period predicted subsequent weight change from 6 to 24 mo. DESIGN: A total of 171 nonobese women were recruited to participate in this longitudinal study in which weight was measured 4 times over 24 mo. The initial 3 weights were used to calculate weight variability with the use of a root mean square error approach to assess fluctuations in weight independent of trajectory. Linear regression analysis was used to examine whether weight variability in the initial 6 mo predicted weight change 18 mo later. RESULTS: Greater weight variability significantly predicted amount of weight gained. This result was unchanged after control for baseline body mass index (BMI) and BMI change from baseline to 6 mo and for measures of disinhibition, restrained eating, and dieting. CONCLUSIONS: Elevated weight variability in young women may signal the degradation of body weight regulatory systems. In an obesogenic environment this may eventuate in accelerated weight gain, particularly in those with a genetic susceptibility toward overweight. Future research is needed to evaluate the reliability of weight variability as a predictor of future weight gain and the sources of its predictive effect. The trial on which this study is based is registered at clinicaltrials.gov as NCT00456131. PMID- 26354536 TI - Best (but oft forgotten) practices: testing for treatment effects in randomized trials by separate analyses of changes from baseline in each group is a misleading approach. AB - Researchers often analyze randomized trials and other comparative studies by separate analysis of changes from baseline in each parallel group. This may be the only analysis presented or it may be in addition to the direct comparison of allocated groups. We illustrate this by reference to 3 recently published nutritional trials. We show why this method of analysis may be highly misleading and may produce type I errors far greater than the 5% that we expect. We recommend direct comparison of means between groups with the use of baseline as a covariate if required. PMID- 26354537 TI - Carotenoids, vitamin A, vitamin C, vitamin E, and folate and risk of self reported hearing loss in women. AB - BACKGROUND: Higher intake of certain vitamins may protect against cochlear damage from vascular compromise and oxidative stress, thereby reducing risk of acquired hearing loss, but data are limited. OBJECTIVE: We prospectively examined the relation between carotenoids, vitamin A, vitamin C, vitamin E, and folate intake and risk of self-reported hearing loss in women. DESIGN: This prospective cohort study followed 65,521 women in the Nurses' Health Study II from 1991 to 2009. Baseline and updated information obtained from validated biennial questionnaires was used in Cox proportional hazards regression models to examine independent associations between nutrient intake and self-reported hearing loss. RESULTS: After 1,084,598 person-years of follow-up, 12,789 cases of incident hearing loss were reported. After multivariable adjustment, we observed modest but statistically significant inverse associations between higher intake of beta carotene and beta-cryptoxanthin and risk of hearing loss. In comparison with women in the lowest quintile of intake, the multivariable-adjusted RR of hearing loss among women in the highest quintile was 0.88 (95% CI: 0.81, 0.94; P-trend < 0.001) for beta-carotene and 0.90 (95% CI: 0.84, 0.96; P-trend < 0.001) for beta cryptoxanthin. In comparison with women with folate intake 200-399 MUg/d, very low folate intake (<200 MUg/d) was associated with higher risk (RR: 1.19; 95% CI: 1.01, 1.41), and higher intake tended to be associated with lower risk (P-trend = 0.04). No significant associations were observed for intakes of other carotenoids or vitamin A. Higher vitamin C intake was associated with higher risk; in comparison with women with intake <75 mg/d, the RR among women with vitamin C intake >=1000 mg/d (mainly supplemental) was 1.22 (95% CI: 1.06, 1.42; P-trend = 0.02). There was no significant trend between intake of vitamin E intake and risk. CONCLUSION: Higher intakes of beta-carotene, beta-cryptoxanthin, and folate, whether total or from diet, are associated with lower risk of hearing loss, whereas higher vitamin C intake is associated with higher risk. PMID- 26354538 TI - Dihydrofolate reductase 19-bp deletion polymorphism modifies the association of folate status with memory in a cross-sectional multi-ethnic study of adults. AB - BACKGROUND: Folate status has been positively associated with cognitive function in many studies; however, some studies have observed associations of poor cognitive outcomes with high folate. In search of an explanation, we hypothesized that the association of folate with cognition would be modified by the interaction of high-folate status with a common 19-bp deletion polymorphism in the dihydrofolate reductase (DHFR) gene. To our knowledge, the cognitive effects of this gene have not been studied previously. OBJECTIVE: We examined the association between cognitive outcomes with the 19-bp deletion DHFR polymorphism, folate status, and their interaction with high or normal plasma folate. DESIGN: This was a pooled cross-sectional study of the following 2 Boston-based cohorts of community living adults: the Boston Puerto Rican Health Study and the Nutrition, Aging, and Memory in Elders study. Individuals were genotyped for the DHFR 19-bp deletion genotype, and plasma folate status was determined. Cognitive outcomes included the Mini-Mental State Examination, Center for Epidemiologic Studies Depression Scale, and factor scores for the domains of memory, executive function, and attention from a set of cognitive tests. RESULTS: The prevalence of the homozygous deletion (del/del) genotype was 23%. In a multivariable analysis, high folate status (>17.8 ng/mL) was associated with better memory scores than was normal-folate status (fourth-fifth quintiles compared with first-third quintiles: beta +/- SE = -0.22 +/- 0.06, P < 0.01). Carriers of the DHFR del/del genotype had worse memory scores (beta +/- SE = -0.24 +/- 0.10, P < 0.05) and worse executive scores (beta = -0.19, P < 0.05) than did those with the del/ins and ins/ins genotypes. Finally, we observed an interaction such that carriers of the del/del genotype with high folate had significantly worse memory scores than those of both noncarriers with high-folate and del/del carriers with normal folate (beta-interaction = 0.26 +/- 0.13, P < 0.05). CONCLUSIONS: This study identifies a putative gene-nutrient interaction that, if confirmed, would predict that a sizable minority carrying the del/del genotype might not benefit from high folate status and could see a worsening of memory. An understanding of how genetic variation affects responses to high-folate exposure will help weigh risks and benefits of folate supplementation for individuals and public health. PMID- 26354539 TI - Differences in postprandial protein handling after beef compared with milk ingestion during postexercise recovery: a randomized controlled trial. AB - BACKGROUND: Protein consumed after resistance exercise increases postexercise muscle protein synthesis rates. To date, dairy protein has been studied extensively, with little known about the capacity of other protein-dense foods to augment postexercise muscle protein synthesis rates. OBJECTIVE: We aimed to compare protein digestion and absorption kinetics, postprandial amino acid availability, anabolic signaling, and the subsequent myofibrillar protein synthetic response after the ingestion of milk compared with beef during recovery from resistance-type exercise. DESIGN: In crossover trials, 12 healthy young men performed a single bout of resistance exercise. Immediately after cessation of exercise, participants ingested 30 g protein by consuming isonitrogenous amounts of intrinsically l-[1-(13)C]phenylalanine-labeled beef or milk. Blood and muscle biopsy samples were collected at rest and after exercise during primed continuous infusions of l-[ring-(2)H5]phenylalanine and l-[ring-3,5-(2)H2]tyrosine to assess protein digestion and absorption kinetics, plasma amino acid availability, anabolic signaling, and subsequent myofibrillar protein synthesis rates in vivo in young men. RESULTS: Beef protein-derived phenylalanine appeared more rapidly in circulation compared with milk ingestion (P < 0.001). The availability of phenylalanine during the 5-h postexercise period tended to be higher after beef (64% +/- 3%) ingestion than after milk ingestion (57% +/- 3%; P = 0.08). Both beef and milk ingestion were followed by an increase in the phosphorylation of mammalian target of rapamycin complex 1 and 70-kDa S6 protein kinase 1 during postexercise recovery. Milk ingestion increased myofibrillar protein synthesis rates to a greater extent than did beef ingestion during the 0- to 2-h postexercise phase (P = 0.013). However, the increase in myofibrillar protein synthesis rates did not differ between milk and beef ingestion during the entire 0- to 5-h postexercise phase (P = 0.114). CONCLUSIONS: Both milk and beef ingestion augment the postexercise myofibrillar protein synthetic response in young men, with a stronger stimulation of myofibrillar protein synthesis during the early postprandial stage after milk ingestion. This trial was registered at www.clinicaltrials.gov as NCT01578590. PMID- 26354541 TI - Taste and the regulation of food intake: it's not just about flavor. PMID- 26354540 TI - Type and amount of dietary protein in the treatment of metabolic syndrome: a randomized controlled trial. AB - BACKGROUND: Food-based dietary patterns emphasizing plant protein that were evaluated in the Dietary Approaches to Stop Hypertension (DASH) and OmniHeart trials are recommended for the treatment of metabolic syndrome (MetS). However, the contribution of plant protein to total protein in these diets is proportionally less than that of animal protein. OBJECTIVE: This study compared 3 diets varying in type (animal compared with plant) and amount of protein on MetS criteria. DESIGN: Sixty-two overweight adults with MetS consumed a healthy American diet for 2 wk before being randomly allocated to either a modified DASH diet rich in plant protein (18% protein, two-thirds plant sources, n = 9 males, 12 females), a modified DASH diet rich in animal protein (Beef in an Optimal Lean Diet: 18.4% protein, two-thirds animal sources, n = 9 males, 11 females), or a moderate-protein diet (Beef in an Optimal Lean Diet Plus Protein: 27% protein, two-thirds animal sources, n = 10 males, 11 females). Diets were compared across 3 phases of energy balance: 5 wk of controlled (all foods provided) weight maintenance (WM), 6 wk of controlled weight loss (minimum 500-kcal/d deficit) including exercise (WL), and 12 wk of prescribed, free-living weight loss (FL). The primary endpoint was change in MetS criteria. RESULTS: All groups achieved ~5% weight loss at the end of the WL phase and maintained it through FL, with no between-diet differences (WM compared with WL, FL, P < 0.0001; between diets, P = NS). All MetS criteria decreased independent of diet composition (main effect of phase, P < 0.01; between diets, P = NS). After WM, all groups had a MetS prevalence of 80-90% [healthy American diet (HAD) compared with WM, P = NS], which decreased to 50-60% after WL and was maintained through FL (HAD, WM vs WL, FL, P < 0.01). CONCLUSIONS: Weight loss was the primary modifier of MetS resolution in our study population regardless of protein source or amount. Our findings demonstrate that heart-healthy weight-loss dietary patterns that emphasize either animal or plant protein improve MetS criteria similarly. This study was registered at clinicaltrials.gov as NCT00937638. PMID- 26354542 TI - Effect of improving dietary quality on carotid intima media thickness in subjects with type 1 and type 2 diabetes: a 12-mo randomized controlled trial. AB - BACKGROUND: People with diabetes are at a heightened risk of cardiovascular disease compared with the general population. To our knowledge, randomized controlled trials investigating the effect of improving dietary quality on carotid intima media thickness, a marker of subclinical atherosclerosis and predictor of cardiovascular disease, have not been conducted in populations with diabetes. OBJECTIVE: We aimed to determine whether increasing fruit (+1 serving; 150 g/d), vegetable (+2 servings; 150 g/d), and dairy (+1 serving; 200-250 g/d) intakes slows 12-mo common carotid artery intima media thickness (CCA IMT) progression, compared with a control group continuing to consume their usual diet, in people with type 1 and type 2 diabetes. DESIGN: A 12-mo randomized controlled trial was conducted. The primary outcome was mean CCA IMT, measured at baseline and 12 mo, with B-mode ultrasound. Participants in the intervention group received counseling from a dietitian at baseline and 1, 3, 6, and 9 mo, and compliance was measured with a food-frequency questionnaire at baseline, 3 mo, and 12 mo. The control group continued consuming their usual diet. RESULTS: In total, 118 participants completed the study. Vegetable (46 g/d; 95% CI: 14, 77 g/d; P < 0.001) and fruit (179 g/d; 95% CI: 119, 239 g/d; P < 0.001) intakes were increased at 3 mo in the intervention group compared with the control group. This increase was not maintained at 12 mo, but intake increased overall in the cohort (fruit, 48 g/d; vegetables, 14 g/d). An increase in dairy consumption was not achieved, but yogurt intake was higher in the intervention group at 3 mo (38 g; 95% CI: 12, 65 g; P < 0.001); this was not maintained at 12 mo. At 12 mo, CCA IMT regressed (mean +/- SD: -0.01 +/- 0.04 mm; P < 0.001), with a greater effect in the treatment group (mean +/- SD: -0.02 +/- 0.04 mm compared with -0.004 +/- 0.04 mm; P = 0.009). CONCLUSION: Improving dietary quality in people with well controlled type 1 and type 2 diabetes may slow CCA IMT progression. This trial was registered at https://www.anzctr.org.au as ACTRN12613000251729. PMID- 26354544 TI - Effects on childhood body habitus of feeding large volumes of cow or formula milk compared with breastfeeding in the latter part of infancy. AB - BACKGROUND: There is controversy over whether a lack of breastfeeding is related to obesity development. OBJECTIVE: We examined the effects of feeding different types of milk in late infancy on childhood growth. DESIGN: A cohort of 1112 term, singleton children (born in 1992) from the Avon Longitudinal Study of Parents and Children, United Kingdom, were studied prospectively. Food records collected at 8 mo of age were used to define the following 5 mutually exclusive feeding groups on the basis of the type and amount of milk consumed: breast milk (BM), <600 mL formula milk/d (FMlow), >=600 mL formula milk/d (FMhigh), <600 mL cow milk/d (CMlow), and >=600 mL cow milk/d (CMhigh). Weight, height, and BMI were measured at 14 time points from birth to 10 y of age, and SD scores (SDSs) were calculated. Dietary energy and macronutrient intakes were available at 7 time points. RESULTS: CMhigh children were heavier than were BM children from 8 mo to 10 y of age with weight differences (after adjustment for maternal education, smoking, and parity) >=0.27 SDSs and an average of 0.48 SDSs. The maximum weight difference was at 18 mo of age (0.70 SDS; 95% CI: 0.41, 1.00 SDS; P = <0.0001). CMhigh children were taller at some ages (25-43 mo; P < 0.01) and had greater BMI SDSs from >=8 mo of age (at 9 y of age; P = 0.001). FMhigh children were heavier and taller than were BM children from 8 to 37 mo of age. There were marked dietary differences between milk groups at 8 mo of age, some of which persisted to 18 mo of age. Adjustments for current energy and protein intakes did not attenuate the growth differences observed. CONCLUSIONS: The feeding of high volumes of cow milk in late infancy is associated with faster weight and height gain than is BM feeding. The feeding of bottle-fed infants with high volumes of cow milk in late infancy may have a persisting effect on body habitus through childhood. PMID- 26354543 TI - Consumption of meat is associated with higher fasting glucose and insulin concentrations regardless of glucose and insulin genetic risk scores: a meta analysis of 50,345 Caucasians. AB - BACKGROUND: Recent studies suggest that meat intake is associated with diabetes related phenotypes. However, whether the associations of meat intake and glucose and insulin homeostasis are modified by genes related to glucose and insulin is unknown. OBJECTIVE: We investigated the associations of meat intake and the interaction of meat with genotype on fasting glucose and insulin concentrations in Caucasians free of diabetes mellitus. DESIGN: Fourteen studies that are part of the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium participated in the analysis. Data were provided for up to 50,345 participants. Using linear regression within studies and a fixed-effects meta-analysis across studies, we examined 1) the associations of processed meat and unprocessed red meat intake with fasting glucose and insulin concentrations; and 2) the interactions of processed meat and unprocessed red meat with genetic risk score related to fasting glucose or insulin resistance on fasting glucose and insulin concentrations. RESULTS: Processed meat was associated with higher fasting glucose, and unprocessed red meat was associated with both higher fasting glucose and fasting insulin concentrations after adjustment for potential confounders [not including body mass index (BMI)]. For every additional 50-g serving of processed meat per day, fasting glucose was 0.021 mmol/L (95% CI: 0.011, 0.030 mmol/L) higher. Every additional 100-g serving of unprocessed red meat per day was associated with a 0.037-mmol/L (95% CI: 0.023, 0.051-mmol/L) higher fasting glucose concentration and a 0.049-ln-pmol/L (95% CI: 0.035, 0.063-ln-pmol/L) higher fasting insulin concentration. After additional adjustment for BMI, observed associations were attenuated and no longer statistically significant. The association of processed meat and fasting insulin did not reach statistical significance after correction for multiple comparisons. Observed associations were not modified by genetic loci known to influence fasting glucose or insulin resistance. CONCLUSION: The association of higher fasting glucose and insulin concentrations with meat consumption was not modified by an index of glucose- and insulin-related single-nucleotide polymorphisms. Six of the participating studies are registered at clinicaltrials.gov as NCT0000513 (Atherosclerosis Risk in Communities), NCT00149435 (Cardiovascular Health Study), NCT00005136 (Family Heart Study), NCT00005121 (Framingham Heart Study), NCT00083369 (Genetics of Lipid Lowering Drugs and Diet Network), and NCT00005487 (Multi-Ethnic Study of Atherosclerosis). PMID- 26354546 TI - Does vitamin D status track through adolescence? AB - BACKGROUND: To our knowledge, no studies have reported on the long-term variability of vitamin D status in adolescents. OBJECTIVE: To determine whether tracking of vitamin D status occurs in healthy adolescents, we assessed the variability of 25-hydroxyvitamin D [25(OH)D] every 2 y over a 10-y period in a longitudinal cohort of adolescents living in Johannesburg, South Africa (latitude 26 degrees S). DESIGN: Healthy adolescents who had blood samples available on >=3 occasions between 11 and 20 y of age were included in the study. Of the cohort of 504 children, 99 met the criteria. The mean 25(OH)D concentration at each time point was measured, and the individual 25(OH)D z scores based on year 11 values were used as the reference. All 25(OH)D concentrations for a subject were measured in a single assay. RESULTS: No significant correlation was found between 25(OH)D in the earlier and later years of adolescence, although significant correlations were found between year 11 and year 13 (r = 0.71, P < 0.0001) and between years 15, 17, and 20 (r >= 0.65, P < 0.0001). The percentage of adolescents whose 25(OH)D concentration changed by >20 nmol/L from year 11 was calculated for all age groups: 12% of the cohort had a change of >20 nmol/L at 13 y of age compared with 46% at 20 y of age. Just more than one-half (53%) of the cohort changed their category of vitamin D status between the ages of 11 and 20 y, and one-third of adolescents changed from being replete to insufficient over the same period. CONCLUSIONS: The data suggest that the measurement of 25(OH)D at a single time point does not reflect the long-term vitamin D status of an adolescent. These findings may cast doubt on the veracity of those studies that suggest an association of vitamin D status with various disease states in which vitamin D status was measured only once. PMID- 26354545 TI - WHO guidelines for a healthy diet and mortality from cardiovascular disease in European and American elderly: the CHANCES project. AB - BACKGROUND: Cardiovascular disease (CVD) represents a leading cause of mortality worldwide, especially in the elderly. Lowering the number of CVD deaths requires preventive strategies targeted on the elderly. OBJECTIVE: The objective was to generate evidence on the association between WHO dietary recommendations and mortality from CVD, coronary artery disease (CAD), and stroke in the elderly aged >=60 y. DESIGN: We analyzed data from 10 prospective cohort studies from Europe and the United States comprising a total sample of 281,874 men and women free from chronic diseases at baseline. Components of the Healthy Diet Indicator (HDI) included saturated fatty acids, polyunsaturated fatty acids, mono- and disaccharides, protein, cholesterol, dietary fiber, and fruit and vegetables. Cohort-specific HRs adjusted for sex, education, smoking, physical activity, and energy and alcohol intakes were pooled by using a random-effects model. RESULTS: During 3,322,768 person-years of follow-up, 12,492 people died of CVD. An increase of 10 HDI points (complete adherence to an additional WHO guideline) was, on average, not associated with CVD mortality (HR: 0.94; 95% CI: 0.86, 1.03), CAD mortality (HR: 0.99; 95% CI: 0.85, 1.14), or stroke mortality (HR: 0.95; 95% CI: 0.88, 1.03). However, after stratification of the data by geographic region, adherence to the HDI was associated with reduced CVD mortality in the southern European cohorts (HR: 0.87; 95% CI: 0.79, 0.96; I(2) = 0%) and in the US cohort (HR: 0.85; 95% CI: 0.83, 0.87; I(2) = not applicable). CONCLUSION: Overall, greater adherence to the WHO dietary guidelines was not significantly associated with CVD mortality, but the results varied across regions. Clear inverse associations were observed in elderly populations in southern Europe and the United States. PMID- 26354547 TI - Validation of the food insulin index in lean, young, healthy individuals, and type 2 diabetes in the context of mixed meals: an acute randomized crossover trial. AB - BACKGROUND: The Food Insulin Index (FII) is a novel classification of single foods based on insulin responses in healthy subjects relative to an isoenergetic reference food. OBJECTIVE: Our aim was to compare day-long responses to 2 nutrient-matched diets predicted to have either high or low insulin demand in healthy controls and individuals with type 2 diabetes (T2DM). DESIGN: Twenty adults (10 healthy adults and 10 adults with T2DM) were recruited. On separate mornings, subjects consumed either a high- or low-FII diet in random order. Diets consisted of 3 consecutive meals (breakfast, morning tea, and lunch), matched for macronutrients, fiber, and glycemic index (GI), but with 2-fold difference in insulin demand as predicted by the FII of the component foods. Postprandial glycemia and insulinemia were measured in capillary plasma at regular intervals over 8 h. RESULTS: As predicted by their GI, there were no differences in glycemic responses between the 2 diets in either group (mean +/- SEM; healthy: 6.2 +/- 0.2 compared with 6.1 +/- 0.1 mmol/L . min, P = 0.429; T2DM: 9.9 +/- 1.3 compared with 10.3 +/- 1.6 mmol/L . min, P = 0.485). Compared with the high-FII diet, mean postprandial insulin response over 8 h was 53% lower with the low-FII diet in healthy subjects (mean +/- SEM; incremental AUCinsulin 31,900 +/- 4100 pmol/L . min compared with 68,100 +/- 11,400 pmol/L . min, P = 0.003) and 41% lower in subjects with T2DM (mean +/- SEM; incremental AUCinsulin 11,000 +/- 1800 pmol/L . min compared with 18,700 +/- 3100 pmol/L . min, P = 0.018). Incremental AUCinsulin was statistically significantly different between diets when groups were combined (P = 0.001). CONCLUSIONS: The FII algorithm may be a useful tool for reducing postprandial hyperinsulinemia in T2DM, thereby potentially improving insulin resistance and beta-cell function. This trial was registered at the Australian New Zealand Clinical Trials Registry as ACTRN12611000654954. PMID- 26354548 TI - Comparative biochemical responses and antioxidant activities of the rabbit urinary bladder to whole grapes versus resveratrol. AB - The objective of this study is to compare the antioxidant activity of a whole grape suspension with the antioxidant activity or pure resveratrol on the effect of hydrogen peroxide (H2O2) on malondialdehyde (MDA) generation, choline acetyltransferase (ChAT) activity, calcium ATPase activity, and sarcoendoplasmic reticular ATPase (SERCA) of the male rabbit urinary bladder. MDA was used as a model for the effect of H2O2 on lipid peroxidation. ChAT, SERCA, and calcium ATPase were evaluated based on their importance in urinary bladder physiology and pathology. Four male rabbit bladders were used. Each bladder was separated into muscle and mucosa, frozen under liquid nitrogen and stored at -80 degrees C for biochemical evaluation. The effect of H2O2 on the enzymes listed above was determined in the presence and absence of either resveratrol or a whole-grape suspension. (1) Resveratrol was significantly more effective than the grape suspension at protecting the bladder muscle and mucosa against peroxidation as quantitated by MDA formation. (2) The grape suspension was significantly more effective at protecting ChAT activity against oxidative stress of the muscle than resveratrol. (3) Neither the grape suspension nor resveratrol were particularly effective at protecting the bladder muscle or mucosa calcium ATPase or SERCA against oxidative stress. (4) ChAT was significantly more sensitive to oxidative stress than either calcium ATPase or SERCA. These data support the idea that the grape suspension protects the mitochondria and nerve terminals to a significantly greater degree than resveratrol which suggests that the activities of the grape suspension are due to the combination of active components found in the grape suspension and not just resveratrol alone. PMID- 26354549 TI - Proposal of nine novel species of the genus Lysinimicrobium and emended description of the genus Lysinimicrobium. AB - Thirteen novel Gram-stain-positive bacteria were isolated from various samples collected from mangrove forests in Japan, and their taxonomic positions were investigated by a polyphasic approach. Phylogenetic analyses based on 16S rRNA gene sequence comparisons showed that the 13 isolates formed a single clade with Lysinimicrobium mangrovi HI08-69T, with a similarity range of 97.6-99.5 %. The peptidoglycan of the isolates was of the A4alpha type with an interpeptide bridge comprising Ser-Glu and an l-Ser residue at position 1 of the peptide subunit. The predominant menaquinone was demethylmenaquinone DMK-9(H4) and the major fatty acid was anteiso-C15 : 0. These chemotaxonomic characteristics corresponded to those of the genus Lysinimicrobium. On the basis of the phenotypic and phylogenetic data, along with average nucleotide identity values among the isolates, we concluded that the 13 isolates should be assigned to the following nine novel species of the genus Lysinimicrobium: Lysinimicrobium aestuarii sp. nov. (type strain HI12-104T = NBRC 109392T = DSM 28144T), Lysinimicrobium flavum sp. nov. (type strain HI12-45T = NBRC 109391T = DSM 28150T), Lysinimicrobium gelatinilyticum sp. nov. (type strain HI12-44T = NBRC 109390T = DSM 28149T), Lysinimicrobium iriomotense sp. nov. (type strain HI12-143T = NBRC 109399T = DSM 28146T), Lysinimicrobium luteum sp. nov. (type strain HI12-123T = NBRC 109395T = DSM 28147T), Lysinimicrobium pelophilum sp. nov. (type strain HI12-111T = NBRC 109393T = DSM 28148T), Lysinimicrobium rhizosphaerae sp. nov. (type strain HI12 135T = NBRC 109397T = DSM 28152T), Lysinimicrobium soli sp. nov. (type strain HI12-122T = NBRC 109394T = DSM 28151T) and Lysinimicrobium subtropicum sp. nov. (type strain HI12-128T = NBRC 109396T = DSM 28145T). In addition, an emended description of the genus Lysinimicrobium is proposed. PMID- 26354551 TI - Task Force 2: Pediatric Cardiology Fellowship Training in Noninvasive Cardiac Imaging: Endorsed by the American Society of Echocardiography and the Society of Pediatric Echocardiography. PMID- 26354550 TI - Axo-Glia Interaction Preceding CNS Myelination Is Regulated by Bidirectional Eph Ephrin Signaling. AB - In the central nervous system, myelination of axons is required to ensure fast saltatory conduction and for survival of neurons. However, not all axons are myelinated, and the molecular mechanisms involved in guiding the oligodendrocyte processes toward the axons to be myelinated are not well understood. Only a few negative or positive guidance clues that are involved in regulating axo-glia interaction prior to myelination have been identified. One example is laminin, known to be required for early axo-glia interaction, which functions through alpha6beta1 integrin. Here, we identify the Eph-ephrin family of guidance receptors as novel regulators of the initial axo-glia interaction, preceding myelination. We demonstrate that so-called forward and reverse signaling, mediated by members of both Eph and ephrin subfamilies, has distinct and opposing effects on processes extension and myelin sheet formation. EphA forward signaling inhibits oligodendrocyte process extension and myelin sheet formation, and blocking of bidirectional signaling through this receptor enhances myelination. Similarly, EphB forward signaling also reduces myelin membrane formation, but in contrast to EphA forward signaling, this occurs in an integrin-dependent manner, which can be reversed by overexpression of a constitutive active beta1-integrin. Furthermore, ephrin-B reverse signaling induced by EphA4 or EphB1 enhances myelin sheet formation. Combined, this suggests that the Eph-ephrin receptors are important mediators of bidirectional signaling between axons and oligodendrocytes. It further implies that balancing Eph-ephrin forward and reverse signaling is important in the selection process of axons to be myelinated. PMID- 26354552 TI - Creating Opportunities to Guide Efficient and Cost-Effective Echocardiography in the Era of Value-Based Cardiac Imaging. PMID- 26354553 TI - Author's Reply. PMID- 26354554 TI - Planning for the Future, Living for the Present. PMID- 26354555 TI - ASE 2015: Boston Was Wicked Awesome! PMID- 26354556 TI - Highlights of the 26(th) Scientific Sessions' Pediatric Congenital Track. PMID- 26354557 TI - Response of transplant recipients to influenza vaccination based on type of immunosuppression: A meta-analysis. AB - Influenza vaccination is widely used in transplant recipients, but there is little known about the significance and correlating factors of its effectiveness. In the current study, we reviewed the existing literature on clinical trials performed in transplant recipients on the effectiveness of influenza vaccination and to evaluate the relevance of the type of immunosuppression employed in these patients on the humoral reaction to the vaccine. A comprehensive search of the literature was performed through Pubmed and Google Scholar to find reports indicating immunogenicity of influenza vaccination in transplant patients. Finally, data from 15 published clinical trials were included in the meta analysis. Data of 947 transplant recipients retrieved from 15 clinical trials investigating the immunogenicity of influenza vaccination were analyzed in this meta-analysis. Analysis showed significantly lower rates of sero-conversion among transplant recipients receiving mycophenolate mofetil (MMF) than other immunosuppressive agents (relative risk: 0.724; 95% confidence interval: 0.596 0.880; P = 0.001). No significant correlation was found with tacrolimus, sirolimus, cyclosporine and azathioprine. Different immunosuppressive agents seem to have different effects on the humoral response rate to influenza vaccination, with MMF having the most significant deleterious effect. The limited and controversial data available in the literature do not support any differential effect for other immunosuppressive agents. PMID- 26354558 TI - Histopathological changes of radial artery wall in patients of chronic kidney disease stage 5 undergoing AV fistula formation and their correlation with serum iPTH levels. AB - Vascular complications arise in uremic patients in the absence of clinically significant atherosclerotic disease. Elevated serum parathyroid hormone (PTH) and abnormal calcium (Ca) and phosphorus (P) balance have been implicated in vascular damage in chronic kidney disease (CKD) patients, but there is lack of histo pathological studies. Patients with CKD stage 5 and 5D who underwent arterio venous fistula were included in this study. Baseline and laboratory parameters including assessment of total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, uric acid, albumin, calcium, phosphorus, intact PTH (iPTH) and vitamin D level were documented. The specimens of the arterial wall were obtained during the procedure and were analyzed. Patients were divided into two groups iPTH <400 (Group A) and iPTH >400 (Group B). Mean intimal thickness (IT) was significantly high in patients of Group B (60.4 +/- 24.1 MU m) as compared with patients of Group A (37.8 +/- 14.9 MUm) (P = 0.003). Vascular calcification was comparable in both groups. The iPTH level was found to be an independent risk factor for high intima thickness (correlation coefficient 0.653) (P-value <0.01). Patients with high (>= 400 pg/mL) iPTH have 8.93 times the risk of developing intimal thickness of >= 60 MU m as compared with patients with low (<400 pg/mL) iPTH (P-value <0.05), with 95% confidence interval of 1.27, 62.61. The mean IT of the radial artery significantly correlated with the iPTH level, while vascular calcification was independent of the iPTH level. Hyperparathyroidism is an important cause of ongoing vascular damage and may contribute to higher vascular events in CKD patients. PMID- 26354559 TI - Association of high-sensitive C-reactive protein and dialysis adequacy with uremic pruritus. AB - Uremic pruritus is a difficult symptom in chronic hemodialysis (HD) patients, and its patho-physiological mechanism remains unknown. To determine the relationship between pruritus and C-reactive protein as well as dialysis adequacy among the HD patients, we studied 241 chronic HD patients in Shiraz dialysis centers, Iran. The patients were selected by convenient sampling and the data were collected using a checklist, interview and lab tests. The mean age of our patients was 53.9 +/- 16.3 years and 128 (53.1%) of them were male. There were 97 (40.2%) patients who complained of pruritus. A significant association was found between high sensitive C-reactive protein and pruritus (P = 0.004). Also, a significant positive relationship was observed between pruritus and dialysis adequacy (P <0.001). Our results suggested a correlation between the inflammatory reaction and pruritus. Furthermore, a positive correlation was found between dialysis adequacy and pruritus. A better understanding of the factors implicated in the cause of uremic pruritus is essential in the development of more-effective treatments and improved quality of life in HD patients. PMID- 26354560 TI - Non-invasive method for preventing intradialytic hypotension: A pilot study. AB - Intradialytic hypotension (IDH) is a life-threatening condition. We evaluated the feasibility of blood volume monitoring (BVM) and blood temperature monitoring (BTM) in preventing IDH in patients prone to the same. Fourteen hemodynamically unstable end-stage renal disease patients who were prone to IDH and unable to achieve dry weight were given BVM treatment twice weekly for two weeks. Forty patients who were not on BVM treatment served as controls. Patients were anemic, had low serum albumin (3.4 +/- 0.43 g/dL) and fluid overload and were edematous. Of the 40 patients in the control group, 18 patients experienced IDH and dialysis had to be terminated. The incidence of IDH was 5% in the control group. In the BVM group, the total volume of fluid removed during hemodialysis was between 2.0 and 4.5 L (mean 3.2 L). By the end of dialysis, the hemo-concentration increased by 34.8%. With use of BVM and BTM, the blood pressure did not drop below 120/80 mm Hg, the dialysis sessions were uneventful and none of the patients suffered symptoms of hypotension. There was a difference of 3 kg between weight achieved and dry weight of the patient, although there was a 14.2% reduction in extracellular water (ECW), 14.5% in plasma fluid and 14.5% decrease in interstitial fluid. Blood volume significantly correlated with post-dialysis intracellular water (ICW) (r = 0.722, P = 0.008) and ECW/ICW ratio (r = 0.698, P = 0.012). There was a significant correlation between systolic blood pressure and ECW (r = 0.615, P = 0.033). Diastolic blood pressure significantly correlated with post-dialysis ECW (r = 0.690, P = 0.008), plasma fluid post-dialysis (r = 0.632, P = 0.027) and interstitial fluid (r = 0.604, P = 0.038). The ECW/ICW ratio was high (1.13 +/- 0.48; control 0.74), implying overhydration and expanded extracellular fluid. BVM should be included in the dialysis protocol where patient compliance to maintenance hemodialysis is poor and patients are constantly in volume overload. PMID- 26354562 TI - Effect of progressive resistive exercise training in improving mobility and functional ability of middle adulthood patients with chronic kidney disease. AB - Patients with chronic kidney disease (CKD) in their middle adulthood are more prone to reduced mobility than younger patients having the same medical condition. Progressive resistive exercise training (PRT) is deemed an effective treatment approach for the management of muscular weakness in patients with CKD. The present review is an attempt to understand the effectiveness of PRT in the mobility and functional ability of patients suffering from CKD. We systematically searched electronic databases, including Medline, Scopus, PubMed, CINAHL, PEDRo and Cochrane, to review the published literature on this subject. Electronic searches were limited to training programs carried out on resistive, aerobic, endurance and therapeutic exercises reporting outcome measures including muscular strength, size, physical function and functional capacity in the clinical population with CKD aged > 40 years. Studies with a minimum duration of eight weeks of exercise training or more were considered eligible for review. The methodological criteria of the included studies were assessed with the PEDro scale. A total of 80 articles were identified using the keywords in the above mentioned databases. However, based on the study's inclusion and exclusion criteria, only 11 articles were finally included. The results of this review substantiate the effectiveness of PRT in patients with CKD. However, further research is warranted in this area due to the limited availability of high quality published evidence. PMID- 26354561 TI - Is CAPD a viable option among ADPKD with end stage renal disease population in India? Its outcomes and economics. AB - Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited renal disease, with 50-75% of these patients requiring renal replacement therapy (RRT). The outcome of peritoneal dialysis (PD) in ADPKD with end-disease renal disease (ESRD) is not clearly defined, more so in developing countries. We conducted a retrospective analysis of the outcomes and economics of PD in these ESRD patients and compared them with other causes of ESRD on PD. Data were reviewed of all the PD patients who were followed-up at our institute from January 2007 to December 2011. The inclusion criteria were ADPKD patients who chose PD as the dialysis modality (Group 1), while age and gender-matched ESRD (other than ADPKD) patients who were started on PD during the same period were considered as the other group (Group 2). A total of 26 ADPKD patients underwent PD with an average size of kidneys among ADPKD ESRD patients of 15.2 + 2.1 cm. The overall peritonitis rates were similar among the compared groups. The median survival for the first peritonitis episodes were 1.2 and 1.8 years (95% confidence interval 0.82-1.91) for the control and ADPKD groups, respectively. The overall patient survival was 22 among PKD while five patients died among the control group. Among PKD, one patient died due to intra-cerebral bleed while one patient had severe cyst hemorrhage and infection, while three others had peritonitis and sepsis. Hernia was observed in four ADPKD patients, once on PD that was surgically corrected and PD was resumed in all. Two patients lost the catheter due to peritonitis while one patient had membrane failure while one underwent surgical exploration due to diverticulosis. PD treatment was not prevented by voluminous kidneys in any of these patients and no patient ceased PD treatment due to insufficient peritoneal space. Besides this, the cost on PD was much less as compared with that on hemodialysis (HD). PD is a reasonable mode of RRT among ADPKD, where HD is not possible or contraindicated with lesser risks to bleeding and infections, and the cost benefit favoring PD in general. PMID- 26354563 TI - Prevalence of peripheral arterial disease diagnosed by ankle brachial index among chronic kidney disease patients in a tertiary care unit. AB - The objective of this study is to determine the prevalence of peripheral vascular disease (PVD) in patients with chronic kidney disease (CKD). Seventy-two patients with CKD stage 3 or above were included in this study. Blood samples were taken from each patient to determine complete blood counts, serum albumin, electrolytes, lipid profile and blood sugar random/fasting. The glomerular filtration rate (GFR) was estimated with the Cockcroft-Gault formula. The ankle brachial index (ABI) was determined to identify the presence of PVD. A standardized Doppler ultrasound device was used. ABI of <0.90 was considered diagnostic of PVD. The mean age of the patients was 53.22 +/- 12.8 years. Forty six patients (63.9%) were male. Twenty-five patients (34.7%) were in stage 3 CKD, 20 patients (27.8%) were in stage 4 CKD and 27 patients (37.5%) were in stage 5 CKD. Twenty patients (27.8%) had an ABI <0.9 and hence had PVD. Of these patients, 13 (18.1%) had mild to moderate PVD with ABI of 0.41-0.90 and seven (9.7%) had severe PVD with ABI of 0.00-0.40. All the baseline parameters including systolic blood pressure (BP), diastolic BP, height, weight, body mass index, GFR, hemoglobin, total blood count, platelets, triglycerides, high-density lipoprotein, low-density lipoprotein and uric acid were not significantly different between patients with and without PVD (P >0.05). However, the mean total cholesterol was significantly higher among patients with PVD. The prevalence of PVD was significantly high in patients with stage 5 CKD (P <0.05). PVD is frequent among patients with CKD based on the ABI as measured by Doppler ultrasound. PMID- 26354565 TI - Microalbuminuria - A better marker in hypertensive disorders of pregnancy. AB - To assess the role of microalbuminuria in pre-eclampsia (PE) as a diagnostic marker, we studied 40 PE cases and 40 normotensive controls at 24 +/- 4 weeks of gestation in women 20-35 years of age. The patients with PE had significant microalbuminuria in comparison with the controls, in addition to deranged renal function tests. The receiver operating characteristic curve showed that microalbuminuria had the highest sensitivity (100%) and good specificity (77.6%). Microalbuminuria had the highest area under the curve (0.869) for both diagnosis of PE and renal function assessment. Microalbuminuria also had a good correlation with systolic blood pressure in the cases with mild grades of renal dysfunction. Microalbuminuria is a specific marker in PE and it also helps to assess the renal function status. Therefore, microalbuminuria may be used in the early diagnosis and management of PE patients in order to reduce the immediate and long-term complications. PMID- 26354564 TI - Metabolic syndrome and chronic kidney disease. AB - To determine the prevalence of metabolic syndrome (MS) in chronic kidney disease (CKD) patients as well as its effects on the progression of CKD, we conducted a prospective, longitudinal study including 180 patients with chronic renal failure followed at the outpatient service of Nephrology at the Saloul's University Hospital of Sousse (Tunisia) over six months. Our study population consisted of 101 men and 79 women. Chronic glomerulonephritis (36.6%) was the most frequent nephropathy. The mean serum creatinine was 249 +/- 200 mmol/L and the mean estimated glomerular filtration rate (eGFR) was 55.8 +/- 49.2 mL/min. Cardiovascular (CV) impairment was found in 27.2% of the patients. The prevalence of MS was 42.2%. Women had significantly more abdominal obesity than men. Subjects with MS were significantly older and predominantly females who had higher blood pressure and body mass index (BMI). CV complications were more frequent among the MS subjects than among the controls. Glycemia, triglycerides, total cholesterol and low-density lipoprotein-cholesterol (LDL-c) were significantly higher in the group of CKD patients with MS. However, the occurrence of MS was not influenced by the nature of nephropathy, the degree of the CKD and the use of renin-angiotensin blockers or statins. In multivariate analysis, predictors of occurrence of MS in our series included older age, female gender and higher BMI and LDL-c levels. The prevalence of MS in patients with CKD is higher than the general population. These patients should receive special multidisciplinary care to limit CV complications. PMID- 26354566 TI - Renal inflammatory response to urinary tract infection in rat neonates. AB - Urinary tract infection (UTI) is one of the most common bacterial infections. Maternal UTI is a risk factor for neonatal UTI. The aim of the present study was to determine the severity of renal inflammation in neonate rats born from mothers with induced UTI. Twelve pregnant rats (Sprague-Dawley) were included in study. The rats were divided into two groups (six rats in each group). In the first group, pyelonephritis was induced in the third trimester of pregnancy and the second group was used as a control group. After delivery, the neonates were divided into three groups based on days after birth (the 1 st, 3 rd and 7 th days after birth). In each group, two neonates of each mother were killed and a midline abdominal incision was made and both kidneys were aseptically removed. On the 7 th day, rat mothers were killed and their kidneys were removed. The preparations were evaluated with a bright field microscope for inflammatory response. Renal pathology showed inflammation in all UTI-induced mothers, but only two cases of neonates (2.1%) showed inflammation in the renal parenchyma. There was no relation between the positive renal culture and the pathological changes. We conclude that neonates with UTI born to UTI-induced mothers showed a lesser inflammatory response. PMID- 26354567 TI - Long-term efficacy of atorvastatin in allograft rejection following renal transplantation: A randomized clinical trial. AB - Statins are a class of drug that can efficiently reduce the level of low-density lipoprotein (LDL) as well as increase the LDL receptors. Several non-lipid lowering effects of this type of drug have been described. It is reported that they have an influence in preventing graft rejection, especially of the acute type. In this study, patients with end-stage renal disease and candidates for kidney transplantation were divided into two groups. Group A (intervention group) received atorvastatin for two weeks prior to their transplant surgery while group B (control group) received placebo. The lipid profile was tested (triglycerides, cholesterol, LDL) in all patients two weeks before the transplantation. After transplantation, drug use was stopped. We also checked the LDL serum levels in patients with raised lipid levels (LDL >100) every two weeks. After this period, the serum lipid levels were checked monthly up to six months. Hyperlipidemia, when present, was controlled by fibrates. Concerning the rejection episodes, there was no significant difference between the two groups. In group A (13 men and nine women), three (14.3%) cases of rejection were observed whereas four (21.3%) cases of rejection were seen in group B (11 men and 10 women) (P = 0.5). Within group A, five (22.7%) cases of delayed graft function were found while four (19%) similar cases were observed in group B (P = 0.7). There was no statistically significant difference concerning delayed graft function between the two groups. Despite all the mechanisms attributed to the probable anti rejection properties of statins, we found no significant correlation with the administration of these drugs before transplantation and the protection against graft rejection episodes. PMID- 26354568 TI - Bedside diagnosis of lymphorrhea after kidney transplantation surgery: A clinical study. AB - The aim of our study is to evaluate the role of pyridium (phenazopyridine) in the early bedside differential diagnosis of urine leak and lymphorrhea. Twenty-five kidney recipients (15 males and ten females, aged between 14 and 62 years) with persisting post-operative fluid drainage from the drain for more than two weeks were enrolled in this study. Creatinine and urea of three samples, namely serum, urine and the drain fluid, were measured. A single dose of 300 mg of pyridium (phenazopyridine) was then administered to all patients. One physician and one nurse who were unaware of the aim of the study checked and evaluated the color of the samples of urine and drain fluid of each patient. In seven patients, the level of creatinine in the urine and drain fluid was similar and in them the color of both samples became orange to red, indicating urine leak from the ureteric anstomotic site. The remainder of the 18 patients did not show any changes in the drain fluid color and the level of creatinine was nearly same in the serum and drain fluid. In a kidney transplant recipient, pyridium can be used as an easy, safe and easily available indicator for diagnosing urine leak in the drain fluid. PMID- 26354569 TI - Hemodialysis versus peritoneal dialysis, which is cost-effective? AB - There is an increasing need for renal replacement therapy due to the growing number of cases with chronic kidney disease leading to end-stage renal disease. Two modalities of dialysis available are hemodialysis (HD) and peritoneal dialysis (PD). In this study, we aimed to compare the financial aspects of HD with PD. A total of 53 patients on HD and 43 patients on PD were included in the study and were assessed for several financial aspects of dialysis. The data collected were analyzed using SPSS-18. A statistically significant difference was noted between the HD and PD groups in the need for diagnostic tests, drugs, hospitalization, etc, with PD being less expensive. We strongly suggest physicians in our area to use PD on a larger number of patients for better financial outcome. PMID- 26354570 TI - An unusual case of a patient who lost his native kidneys and renal allograft from cholesterol crystal emboli. AB - Cholesterol crystal emboli (CCE) syndrome involving native kidneys is an underdiagnosed condition. CCE is rare in renal allografts. It may present with acute kidney injury, but usually not acute graft loss. CCE should be considered in patients with a history of atherosclerosis and an invasive arterial procedure who present with acute or chronic renal allograft dysfunction. Therapy for CCE is mainly supportive and carries a high rate of mortality. To the best of our knowledge, this is the first reported case of a patient who lost his native kidneys and renal allograft due to CCE arising from his own vasculature. PMID- 26354571 TI - A case of primary renal allograft dysfunction due to myeloma cast nephropathy. AB - We report a rare case of primary renal allograft dysfunction due to myeloma cast nephropathy in a patient with no overt clinical features of multiple myeloma preceding his transplantation. A 45-year-old man on hemodialysis for six months for end-stage kidney disease due to presumed chronic glomerulonephritis developed immediate graft dysfunction post-transplantation. The graft biopsy was diagnostic of myeloma cast nephropathy. Other criteria for lambda light chain multiple myeloma were fulfilled with immunofixation electrophoresis and bone marrow biopsy. He was treated with plasmapheresis, bortezomib and high-dose dexamethasone. However, the patient succumbed to septicemia on the 37 th post operative day. This is probably the first report of primary renal allograft dysfunction due to myeloma cast nephropathy diagnosed within the first week post transplanation in a patient with unrecognized multiple myeloma. PMID- 26354572 TI - Prolonged hypophosphatemia following parathyroidectomy in chronic hemodialysis patients. AB - Secondary hyperparathyroidism (SHPT) is a common problem in patients with end stage renal disease. In cases with severe and resistant SHPT, surgical parathyroidectomy (PTX) is recommended. Hungry bone syndrome (HBS) following surgical PTX is most often associated with hypocalcemia and hypophosphatemia. The mechanisms for the HBS are not clear, and a method for its prevention has not been established. We present three hemodialysis patients with persistant hypophosphatemia after PTX. In our parathyroidectomized patients, hypocalcemia could be corrected with calcium and vitamin D treatment, but hypophosphatemia continued for eight months in one patient and in two other patients until the last visit (10 and 2 months, respectively). Predisposing factors such as old age, diabetes mellitus and parathyroid adenoma were not found in our patients. All three patients were younger (<35 years old) and anuric. Hemodialysis durations were seven, three and two years. In summary, HBS presented with hypocalcemia, and especially hypophosphatemia cannot be developed uncommonly and may persist for a long time following PTX in HD patients. PMID- 26354573 TI - Acute kidney injury: A rare cause. AB - We present a young lady who consumed hair dye, which contained paraphenylene diamine (PPD), as a means of deliberate self-harm. This resulted in severe angio neurotic edema for which she had to be ventilated, and thereafter developed rhabdomyolysis leading to acute kidney injury (AKI). The unusual aspect was that the patient continued to have flaccid quadriparesis and inability to regain kidney function. Renal biopsy performed 10 weeks after the dye consumption revealed severe acute tubular necrosis with myoglobin pigment casts. This suggests that PPD has a long-term effect leading to ongoing myoglobinuria, causing flaccid paralysis to persist and preventing the recovery of AKI. In such instances, timely treatment to prevent AKI in the form alkalinization of urine should be initiated promptly. Secondly, because PPD is a nondialyzable toxin, and its long-term effect necessitates its speedy removal, hemoperfusion might be helpful and is worth considering. PMID- 26354574 TI - A rare case of type-I auto-immune hepatitis and thyroiditis presenting with crescentic glomerulonephritis. AB - A middle-aged female patient with a past history of non-alcoholic liver disease and hypothyroidism presented with swelling of the body, off and on, for six months and rapidly worsening renal function. Renal biopsy showed crescentic glomerulonephritis with negative immunofluorescence. Serological tests were positive for anti-thyroglobulin, anti-nuclear antibody (1:80), p-anti-neutrophil cytoplasmic antibodies; gamma globulin was 5.23 g/dL and viral markers were negative. The patient was diagnosed to have autoimmune hepatitis type-1 and treated with injection methylprednisolone pulse (500 mg/day for 3 days) and maintained on oral steroids and azathioprine 100 mg. She responded dramatically to this treatment and has remained in complete remission at last follow-up. PMID- 26354575 TI - Schimke immune-osseous dysplasia: A case report. AB - Schimke immune-osseous dysplasia (SIOD) is a rare autosomal recessive disorder characterized by spondylo-epiphyseal dysplasia (SED), progressive renal insufficiency beginning as steroid-resistant nephrotic syndrome (SRNS) and defective cellular immunity. This article reports a case from Egypt with a mild form of SIOD. A 14.5-year-old male patient presented with disproportionate short stature, SRNS (focal and segmental glomerulosclerosis), laboratory evidence of cellular immune deficiency and radiologic characteristics of SED. He died at the age of 16.5 years with bone marrow failure and severe pneumonia. To the best of our knowledge, this is the first case of SIOD to be reported from Egypt. PMID- 26354576 TI - Colchicine therapy in amyloidosis related with plasmacytic Castleman disease presenting with nephrotic syndrome. AB - Castleman disease (CD) is a neoplasm that presents with single or multiple lymphadenopathy. The disease is characterized by fever, weight loss, anemia, polyclonal hyperglobulinemia, splenomegaly, thrombocytosis and peripheral lymphadenopathy. In this paper, we report a young man with plasmacytic type CD and amyloid A (AA) deposition who presented with intra-abdominal mass and nephrotic syndrome. He was successfully treated with colchicine following surgery. PMID- 26354577 TI - Primary synovial sarcoma of the kidney. AB - Primary synovial sarcoma (SS) of the kidney is a very rare disease as well as a diagnostic dilemma. Here, we present a case of a 60-year-old male clinically diagnosed as renal cell carcinoma. The radical nephrectomy specimen showed a well circumscribed renal mass of approximately 13 cm * 9 cm * 7 cm. The cut-surface of the mass was tawny and firm, with cystic areas, and also showed focal hemorrhage and necrosis. Histologically, the tumor was composed of spindle cells arranged in the intersecting fascicles, alternating with hypocellular areas suggestive of monophasic synovial sarcoma. Morphological and immunohistochemical features were compatible with the diagnosis of SS of the kidney. PMID- 26354578 TI - Candida-associated pseudo-aneurysm of the transplant renal artery presenting as malignant hypertension and managed successfully without nephrectomy. PMID- 26354579 TI - Novel H1N1 influenza infection among post-renal transplantation subjects: A mini review. PMID- 26354580 TI - Renal artery anastomosis to internal or external iliac artery in kidney transplant patients. PMID- 26354581 TI - Recurrent ascites secondary to endometriosis in a dialysis patient. PMID- 26354582 TI - Backache in patients on maintenance hemodialysis: Beware of spinal tuberculosis. PMID- 26354583 TI - Comment to case report encapsulating peritoneal sclerosis (EPS): Presentation without preceding symptoms. PMID- 26354584 TI - Acute interstitial nephritis overlapping chronic renal damage. PMID- 26354585 TI - Endovascular repair of iatrogenic subclavian artery pseudo-aneurysm. PMID- 26354586 TI - Oxalate nephropathy after Jejuno-Ileal bypass surgery. PMID- 26354587 TI - Epidemiology and referral patterns of patients with chronic kidney disease in the Emirate of Abu Dhabi. AB - According to estimates, the dialysis prevalence in Abu Dhabi is around 370 per million population. The annual growth is 12-15% and the dialysis population is likely to double in the next five years. Most patients present to dialysis as an emergency and only 2.7% have an arteriovenous fistula at the first dialysis. The prevalence of chronic kidney disease (CKD) in the Emirate is undefined. A study of the epidemiology of CKD and referral patterns was undertaken. SEHA, the Abu Dhabi Health Service delivery company, has a unified computer system containing all measurements made in its laboratories. This study considered all serum creatinine measurements performed between 1 September 2011 and 31 October 2012 from outpatient departments or emergency rooms. The estimated glomerular filtration rate (eGRF) was calculated using the Modification of Diet in Renal Disease formula (the Schwartz formula was used for children). We identified 331,360 samples from 212,314 individuals. The mean serum creatinine was 61 +/- 48 MUmol/L in females (59 +/- 43 MUmol/L in Emiratis, 63 +/- 54 MUmol/L in expatriates) and 87 +/- 69 MUmol/L in males (80 +/- 59 MUmol/L in Emiratis, 92 +/ 74 MUmol/L in expatriates). Among Emiratis, 4.6% of males and 2.8% of females had an eGFR between CKD 3 and 5. Among expatriates, 4.2% of males and 3.2% of females had an eGFR between CKD 3 and 5. On average, eight months elapsed before a patient with CKD 3, and three months for a patient in CKD 5, to attend the nephrology clinic. This study has defined the prevalence of CKD within Abu Dhabi and demonstrated the need to improve identification and referral of CKD patients. Possible solutions include campaigns to increase public and physician awareness of CKD. PMID- 26354588 TI - Diabetic kidney disease and vascular comorbidities in patients with type 2 diabetes mellitus in a developing country. AB - Type 2 diabetes mellitus (T2DM) is associated with an increased risk of progression toward end-stage renal disease and cardiovascular (CV) risk mortality. To investigate this association, we studied 637 patients with T2DM in the Eastern area of Morocco. The mean follow-up period was 42 +/- 11 months. At the baseline visit, 22.8%, 59.1% and 18.1% of the patients had normo-albuminuria, micro-albuminuria and macro-albuminuria, respectively. Of all patients, 51.6% had a history of hypertension and 37.4% had hypertension on admission. At the end of follow-up, rapid progression (estimated glomerular filtration rate >5 mL/min/1.73 m2 /year) was observed in 24.1% of the cases and the frequency of occurrence of CV events was 5%, 18.5% and 32.5% in the normo-, micro- and macro-albuminuria groups, respectively (P <0.001). In multivariate analysis, arterial hypertension was identified as an independent risk factor related to diabetic kidney disease (DKD, P = 0.04) and occurrence of CV events (P = 0.02), while albuminuria was not identified as an independent risk factor, either for DKD or for the occurrence of CV events. Our study found that hypertension was an independent risk factor for the DKD and the occurrence of the CV events in T2DM patients. PMID- 26354589 TI - Kidney biopsy in the Military Hospital of Morocco: Complications and histopathological findings. AB - Epidemiological studies on renal biopsies are necessary to establish the pattern and trends of renal diseases in a particular geographic area. In this retrospective study, we reviewed the medical records, histopathology findings and complications of renal biopsy in a region of Morocco. We studied a total of 130 native kidney biopsies taken between January 2008 and January 2012. All biopsies were examined by light microscopy and immunofluorescence microscopy. There were 86 males (66.2%) and 44 females (33.8%), with a mean patient age of 44.82 +/- 17.86 (range 8-86) years. The most common indications of renal biopsy was nephritic syndrome (61.5%), followed by renal failure of unknown etiology (30.8%) and asymptomatic urinary abnormalities (5.4%). Primary glomerulonephritis (PGN) was found in 60 (46.2%) of the patients. Among the PGN cases, the most common one was membranous nephropathy (MN) (12.3%). Secondary glomerular disease (SGN) accounted for 48 (36.9%) of the cases. The most common SGN was lupus nephritis (LN) (10%). Tubulointerstitial disease [13 (10%)] and vascular disease [9 (6.9%)] were less common. The most common complications of the procedure were pain at the biopsy site in 12.3%, gross hematuria in 12.3%, perirenal hematoma in 7.7% and hematuria requiring nephrectomy in 0.8% of the patients. The most common indication for renal biopsy was nephrotic syndrome, MN was the most frequent PGN and LN was the most frequent SGN in our report. PMID- 26354590 TI - A cross-sectional study of dialysis practice-patterns in patients with chronic kidney disease on maintenance hemodialysis. AB - We studied the dialysis practice-patterns with regard to various aspects of chronic kidney disease (CKD) stage 5D, like anemia, mineral bone disease, vaccination, hospitalization, hypertension and cost of therapy. Four hundred and sixty-four adult hemodialysis (HD) patients from various dialysis centers of Mumbai were included in the study. The mean age of the study patients was 47.2 years. Temporary dialysis catheters were the most common initial vascular access. Thirteen percent of prevalent HD patients were on temporary catheters; 33% of patients had history of failure of arterio-venous fistula. The most common cause of failure was access thrombosis. About 75% of the patients had hemoglobin <11 g/dL and 35% had uncontrolled blood pressure. The prevalence of positive hepatitis B surface antigen and anti-hepatitis C virus antibody was 6% and 2%, respectively. The average cost of HD treatment was approximately 6100 Indian rupees (about US $100). HD is helpful in treating many of the clinical manifestations of CKD and postpones otherwise imminent death. However, dialysis treatment is no panacea to renal failure; HD patients have higher hospitalization rates and lower quality of life than the general population. The therapy itself brings with it a unique set of problems, such as vascular access-related complications, which cause significant mortality and morbidity. This study was a study of the current HD practices. The primary goal of this cross-sectional observational study is to understand dialysis practices and obtain data that can be used to improve care in the future. PMID- 26354592 TI - Acute glomerulonephritis in children of the Niger Delta region of Nigeria. AB - A three-year retrospective study was conducted to determine the incidence, pattern of presentation and other clinical and biochemical features as well as outcome of treatment of patients admitted with acute glomerulonephritis at the Delta State University Teaching Hospital, Oghara and GN Children's Clinic, Warri. The case notes of all the children who presented with renal diseases from January 2010 to December 2012 were retrieved and those with acute glomerulonephritis were analyzed. A total of 20 patients (13 male and seven female) with acute glomerulonephritis were seen during the three-year period under review. Twelve patients (60%) were from the low socioeconomic class, six (30%) from the middle class and only two (10%) were from the high-income group. The presentation of the illness was most common between October and January. The age range of the patients was three to 13 years, with an average age of eight years. Seventeen (85%) of the patients were in the school-going age group (>5 years to 10 years). The most common symptom/sign noted was anemia in 90% of the patients, followed by oliguria/anuria and edema seen in 80% of the patients. Seventy percent of the patients had cola-colored urine, while 55% had hypertension. Some patients gave a history suggestive of previous streptococcal infection. More patients had sore throat (25%) than skin infection (10%). All the patients had proteinuria, while 90% had hematuria. The most common complication was acute kidney injury, seen in eight (40%) of the patients, followed by hypertensive encephalopathy, which occurred in three (15%) patients. Most patients (60%) were hospitalized for one to two weeks. The outcome of the management of these patients showed 14 (70%) of the patients recovered fully while three (15%) had persistent hematuria and two (10%) had persistent proteinuria. Ninety-five percent of the patients recovered from the acute illness and one patient (5%), a boy aged nine years old, died. PMID- 26354591 TI - Spectrum of IgA nephropathy in a single center. AB - Immunoglobulin A (IgA) nephropathy (IgAN) is the most common biopsy-proven primary glomerular disease in the world and a major contributor to the worldwide burden of endstage renal failure, with a wide geographical variation. To determine the incidence, clinical profile and histological pattern of IgAN in our institute, we reviewed all the patients who had native kidney biopsies with the diagnosis of primary IgAN during the period from 1998 to 2009 in the context of the clinical features. A total of 116 patients with IgAN were finally analyzed; 85 (73%) of the patients were male, the mean age of the patients was 29.2 +/- 12.2 (range 10-70) years and the mean duration of disease was 10.4 +/- 18.7 months (median: 2 months). Hypertension was present in 74 (63.2%) cases. Gross hematuria was rare. The most common clinical presentation was nephrotic syndrome, followed by chronic renal failure. The mean proteinuria level was 2.5 +/- 2.3 g/day (median: 1.7 g/day) and the mean serum creatinine level was 3.04 +/- 3.3 mg/dL (median:1.7 mg/dL). The morphological sub-classification (Haas): Class I was the most common (44.4%), followed by class V (23%). IgA co-deposition with C3 and lambda was the most common finding in the immunofluorescence study. The glomerular filtration rate decreased with advanced histological damage. The incidence of IgAN was 7.5%, which is lower as compared with studies from elsewhere. IgAN in our population had a more severe clinical presentation. PMID- 26354593 TI - Interdisciplinary collaboration in the use of a music-with-movement intervention to promote the wellbeing of people with dementia and their families: Development of an evidence-based intervention protocol. AB - The music-with-movement intervention is particularly suitable for people with dementia because their gross motor ability is preserved until the later stage of dementia. This study examines the effect of music-with-movement on reducing anxiety, sleep disturbances, and improving the wellbeing of people with dementia. This paper reports the first stage of the study - developing the intervention protocol that staff can use to teach family caregivers. A registered music therapist developed a music-with-movement protocol and taught staff of two social service centers over five weekly 1.5 h sessions, with center-in-charges (social workers and occupational therapists) and our research team joining these sessions to provide comments from their professional perspective. Each discipline had different expectations about the content; therefore, numerous meetings and discussions were held to bridge these differences and fine-tune the protocol. Few healthcare professionals doubt the merits of interdisciplinary collaboration at all levels of health promotion. In practice, interdisciplinary collaboration is complex and requires commitment. Openness and persistence is required from all stakeholders to achieve a successful intervention for consumers. PMID- 26354595 TI - Tiered approach into practice: scientific validation for chromatography-based assays in early development - a recommendation from the European Bioanalysis Forum. AB - The principles of tiered approach have been part of the bioanalytical toolbox for some years. Nevertheless, an in spite of many valuable discussions in industry, they remain difficult to apply in a harmonized way for a broad array of studies in early drug development where these alternative approaches to regulated validation would make sense. The European Bioanalysis Forum has identified the need to proposes some practical workflows for five categories of studies for chromatography based assays where scientific validation will allow additional freedom while safeguarding scientific rigor and robust documentation: quantification of metabolites in plasma in relation to ICH M3(R2), urine analysis, tissue homogenate analysis, and preclinical and clinical studies in early stages of drug development. The recommendation would introduce a common language and harmonized best practice for these study categories and can help to refocus towards optimized scientific and resource investments for bioanalysis in early drug development. PMID- 26354596 TI - Analytical applications of nanoparticles in MALDI-MS for bioanalysis. AB - Recently, the rapid development of nanotechnology has enabled the analytical community to integrate processes with MALDI-MS for the analysis of various biomolecules. This article presents the recent progress on nanomaterials as extracting probes in single-drop microextraction, in liquid-liquid microextraction and as affinity probes for the enrichment of trace level biomolecules prior to their identification by MALDI-MS. PMID- 26354594 TI - Age-independent myocardial infarct quantification by signal intensity percent infarct mapping in swine. AB - PURPOSE: To test whether signal intensity percent infarct mapping (SI-PIM) accurately determines the size of myocardial infarct (MI) regardless of infarct age. MATERIALS AND METHODS: Forty-five swine with reperfused MI underwent 1.5T late gadolinium enhancement (LGE) magnetic resonance imaging (MRI) after bolus injection of 0.2 mmol/kg Gd(DTPA) on days 2-62 following MI. Animals were classified into acute, healing, and healed groups by pathology. Infarct volume (IV) and infarct fraction (IF) were determined by two readers, using binary techniques (including 2-5 standard deviations [SD] above the remote, and full width at half-maximum) and the SI-PIM method. Triphenyl-tetrazolium-chloride staining (TTC) was performed as reference. Bias (percent under/overestimation of IV relative to TTC) of each quantification method was calculated. Bland-Altman analysis was done to test the accuracy of the quantification methods, while intraclass correlation coefficient (ICC) analysis was done to assess intra- and interobserver agreement. RESULTS: Bias of the MRI quantification methods do not depend on the age of the MI. Full-width at half-maximum (FWHM) and SI-PIM gave the best estimate of MI volume determined by the reference TTC (P-values for the FWHM and SI-PIM methods were 0.183, 0.26, 0.95, and 0.073, 0.091, 0.73 in Group 1, Group 2, and Group 3, respectively), while using any of the binary thresholds of 2-4 SDs above the remote myocardium showed significant overestimation. The 5 SD method, however, provided similar IV compared to TTC and was shown to be independent of the size and age of MI. ICC analysis showed excellent inter- and intraobserver agreement between the readers. CONCLUSION: Our results indicate that the SI-PIM method can accurately determine MI volume regardless of the pathological stage of MI. Once tested, it may prove to be useful for the clinic. PMID- 26354597 TI - SPME techniques for biomedical analysis. AB - Biomedical analyses of drugs and their metabolites are important in new drug development, therapeutic drug monitoring and forensic toxicology. In these analyses, sample preparation is very important to isolate target compounds from complex biological matrices and markedly influences the reliability and accuracy of determination. SPME is a simple and convenient sample preparation technique that has enabled automation, miniaturization and high-throughput performance. This article focuses on current developments, their biomedical applications and future trends with emphasis on new extraction devices using selective polymer coating materials in novel SPME techniques, including fiber SPME, in-tube SPME and related techniques. PMID- 26354598 TI - Stir bar sorptive extraction applied to the analysis of biological fluids. AB - Stir bar sorptive extraction (SBSE) is a sample preparation technique, which is used for the extraction as well as the preconcentration of organic substances from various aqueous matrices, prior to the determination of the analytes with a separation technique, such as LC or GC, coupled to different detectors. Since 1999, when SBSE was first developed by Sandra and co-workers, SBSE has been used in the analysis of samples of environmental, food, pharmaceutical and biomedical origin. In this article, we focus on the application of SBSE in biological fluids. PMID- 26354599 TI - Microextraction with phases containing nanoparticles. AB - In this article, the state of the art of microextraction techniques that involve nanoparticles or nanomaterials (NPs) is reviewed, with special emphasis on the applications described in the biomedical field. The uses and advantages of the different types of NPs such as carbon nanotubes (either single- and multi-walled) and other carbon-based materials, metallic NPs, including gold, silver and magnetic NPs, and silica NPs are summarized. The main strategies used to modify the selectivity, extractive capacity and/or the stability of NPs through a chemical reaction are also reviewed. The potential advantages of NPs in different forms of off-line and on-line microextraction are discussed, and illustrative examples of application in the biomedical field are shown. PMID- 26354600 TI - A Comparison of Homeless Male Veterans in Metropolitan and Micropolitan Areas in Nebraska: A Methodological Caveat. AB - This study explored differences between homeless male veterans in metropolitan and micropolitan cities in Nebraska on sociodemographic, housing, clinical, and psychosocial characteristics as well as health service use. A convenience sample of 151 homeless male veterans (112 metropolitan, 39 micropolitan) were recruited from Veterans Affairs facilities and area shelters in Omaha, Lincoln, Grand Island, and Hastings in Nebraska. Research staff conducted structured interviews with homeless veterans. Results showed that compared to homeless veterans in metropolitans, those in micropolitans were more likely to be White, unmarried, living in transitional settings, and were far more transient but reported greater social support and housing satisfaction. Veterans in micropolitans also reported more medical problems, diagnoses of anxiety and personality disorders, and unexpectedly, were more likely to report using various health services and less travel time for services. Together, these findings suggest access to homeless and health services for veterans in micropolitan areas may be facilitated through Veterans Affairs facilities and community providers that work in close proximity to one another. Many homeless veterans in these areas are transient, making them a difficult population to study and serve. Innovative ways to provide outreach to homeless veterans in micropolitan and more rural areas are needed. PMID- 26354601 TI - Improving health outcomes through concurrent HIV program scale-up and health system development in Rwanda: 20 years of experience. AB - The 1994 genocide against the Tutsi destroyed the health system in Rwanda. It is impressive that a small country like Rwanda has advanced its health system to the point of now offering near universal health insurance coverage. Through a series of strategic structural changes to its health system, catalyzed through international assistance, Rwanda has demonstrated a commitment towards improving patient and population health indicators. In particular, the rapid scale up of antiretroviral therapy (ART) has become a great success story for Rwanda. The country achieved universal coverage of ART at a CD4 cell count of 200 cells/mm(3) in 2007 and increased the threshold for initiation of ART to <=350 cells/mm(3) in 2008. Further, 2013 guidelines raised the threshold for initiation to <=500 cells/mm(3) and suggest immediate therapy for key affected populations. In 2015, guidelines recommend offering immediate treatment to all patients. By reviewing the history of HIV and the scale-up of treatment delivery in Rwanda since the genocide, this paper highlights some of the key innovations of the Government of Rwanda and demonstrates the ways in which the national response to the HIV epidemic has catalyzed the implementation of interventions that have helped strengthen the overall health system. PMID- 26354603 TI - Lest we forget: Remembering the Great War. PMID- 26354602 TI - The Impact of a Signalized Crosswalk on Traffic Speed and Street-Crossing Behaviors of Residents in an Underserved Neighborhood. AB - Infrastructure improvements such as pedestrian crosswalks that calm traffic and increase access to physical activity opportunities could alleviate important barriers to active living in underserved communities with outdated built environments. The purpose of this study was to explore how the built environment influences street-crossing behaviors and traffic speeds in a low-income neighborhood with barriers to active living in Columbia, Missouri. In 2013, a signalized pedestrian crosswalk and 400-ft-long median was constructed along a busy 5-lane, high-speed arterial highway linking low-income housing with a park and downtown areas. Data collection occurred prior to June 2012, and after June 2013, completion of the project at the intervention site and control site. Direct observation of street-crossing behaviors was performed at designated intersections/crosswalks or non-designated crossing points. Traffic volume and speed were captured using embedded magnetic traffic detectors. At the intervention site, designated crossings increased at the new crosswalk (p < 0.001), but not at non-designated crossings (p = 0.52) or designated crossings at intersections (p = 0.41). At the control site, there was no change in designated crossings (p = 0.94) or non-designated crossings (p = 0.79). Motor vehicles traveling above the speed limit of 35 mph decreased from 62,056 (46 %) to 46,256 (35 %) (p < 0.001) at the intervention site and increased from 57,891 (49 %) to 65,725 (59 %) (p < 0.001) at the control site. The installation of a signalized crosswalk facilitated an increase in safe street crossings and calmed traffic volume and speed in an underserved neighborhood. We believe these findings have significant public health implications that could be critical to advocacy efforts to improve infrastructure projects in similar communities. PMID- 26354604 TI - The Pediatric Outcomes Data Collection Instrument for a Polish sample with juvenile idiopathic arthritis: psychometric properties of proxy version. AB - AIM: The aims of the study were to investigate the psychometric properties of the Pediatric Outcomes Data Collection Instrument (PODCI) for parents of children aged 2-10 years, in a Polish sample of juvenile idiopathic arthritis and to compare the results from children with chronic arthritis to the results from a normative sample. METHODS: The sample consisted of the parents of 29 (72.5%) girls and 11 (27.5%) boys. The ages of the children ranged from 2 to 10 years (mean 6.50, standard deviation [SD] 2.63). Disease course was classified as oligoarticular (n = 26, 65%) and polyarticular (n = 14, 35%). Parents who took part in the intrarater reliability study completed the Polish version of PODCI twice. The PODCI consists of the following subscales: Upper Extremity and Physical Function, Transfer and Mobility Tasks, Sports/Physical Functioning, Pain/Comfort, and Happiness. A Global Functioning Scale consists of the mean of the 'mean of items' values for the first four scales. RESULTS: The mean standarized Global Functioning Scale was 81.79 (SD 13.45), whereas the mean normative Global Functioning Scale score equaled 33.65 (SD 18.19). Cronbach's alpha value of the Global Functioning Scale was excellent and equaled 0.81. The effect size concerning the Global Functioning Scale equaled 0.123. Test-retest reliability equaled 0.98, whereas intrarater reliability (intraclass correlation coefficient) equaled 0.99. CONCLUSIONS: The translation and cross-cultural adaptation of the PODCI questionnaire provides a Polish equivalent to assess physical function in children with chronic arthritis. PMID- 26354605 TI - Japanese sake yeast supplementation improves the quality of sleep: a double-blind randomised controlled clinical trial. AB - Activation of adenosine A2a receptors in cerebral neurons induces sleep in various mammals. It was previously found that Japanese sake yeast enriched in adenosine analogues activates A2a receptors in vitro and induces sleep in mice. Here it is reported that sake yeast activated A2a receptors in a cultured human cell line and improved human sleep quality in a clinical trial. Sake yeast activated A2a receptors in HEK cells in a dose-dependent manner with an EC50 of 40 MUg mL(-1), and the activation was attenuated almost completely by the A2a receptor antagonist ZM241385 with an IC50 of 73 nm. In a double-blind placebo controlled crossover clinical study, 68 healthy participants ingested tablets containing either 500 mg of sake yeast powder or a placebo (cellulose) 1 h before sleep for 4 days. Electroencephalograms were recorded during sleep at home with a portable device for 4 week days. Electroencephalogram analyses revealed that sake yeast supplementation significantly (P = 0.03) increased delta power during the first cycle of slow-wave sleep by 110%, without changing other sleep parameters. Sake yeast supplementation also significantly increased growth hormone secretion in the urine on awakening by 137% from 3.17 +/- 0.41 (placebo) to 4.33 +/- 0.62 (sake yeast) pg mg(-1) creatinine (P = 0.03). Subjective sleepiness (P = 0.02) and fatigue (P = 0.06) in the morning were improved by sake yeast. Given these benefits and the absence of adverse effects during the study period, it was concluded that sake yeast supplementation is an effective and safe way to support daily high-quality, deep sleep. PMID- 26354607 TI - Assessment of the hybridization between rhesus (Macaca mulatta) and long-tailed macaques (M. fascicularis) based on morphological characters. AB - OBJECTIVES: Hybridization between rhesus (Macaca mulatta) and long-tailed (M. fascicularis) macaques has become a focal point of interest. The majority of such studies have evaluated their genetics, but not their morphological characters. MATERIALS AND METHODS: We analyzed morphological characters of eight free-ranging populations of Indochinese rhesus and long-tailed macaques distributed at the proposed hybrid zone (15.75-21.58 degrees N) in comparison with one population each of Chinese and Indian-derived rhesus macaques and three populations of Sundaic long-tailed macaques. RESULTS: Chinese and Indian rhesus macaques had a heavier body mass, longer crown-rump length, shorter relative facial length and relative tail length, and a greater contrast of reddish and yellowish dorsal pelage color than the Sundaic long-tailed macaques for which the latter three parameters could be used to visually discriminate between the two species. Although the morphological characters of Indochinese rhesus and long-tailed macaques were intermediate between the Chinese/Indian rhesus and Sundaic long tailed macaques, they were more similar to their respective conspecifics. The species-specific characters of a shorter tail (<70%) and a bipartite pelage color pattern were retained in the Indochinese rhesus macaques while the longer tail (>90%) and no bipartite pattern was found in the Indochinese long-tailed macaques. No morphological cline was observed across the species and the variations were abrupt to some extent. DISCUSSION: The hybridization between rhesus and long-tailed macaques may be results of multiple contacts and isolations over a long period of time, thus their evolutionary history should not be drawn solely by genetic or morphological analysis. PMID- 26354606 TI - Molecular Basis for the Regulation of Transcriptional Coactivator p300 in Myogenic Differentiation. AB - Skeletal myogenesis is a highly ordered process which specifically depends on the function of transcriptional coactivator p300. Previous studies have established that Akt/protein kinase B (PKB), a positive regulator of p300 in proliferating cells, is also important for proper skeletal muscle development. Nevertheless, it is not clear as to how the p300 is regulated by myogenic signaling events given that both p300 and Akt are involved in many cellular processes. Our studies revealed that the levels of p300 protein are temporally maintained in ligand enhanced skeletal myocyte development. Interestingly, this maintenance of p300 protein is observed at the stage of myoblast differentiation, which coincides with an increase in Akt phosphorylation. Moreover, regulation of p300 during myoblast differentiation appears to be mediated by Akt signaling. Blunting of p300 impairs myogenic expression and myoblast differentiation. Thus, our data suggests a particular role for Akt in myoblast differentiation through interaction with p300. Our studies also establish the potential of exploiting p300 regulation and Akt activation to decipher the complex signaling cascades involved in skeletal muscle development. PMID- 26354608 TI - Impact of Hemodynamic Instability and Organ Malperfusion in Elderly Surgical Patients Treated for Acute Type A Aortic Dissection. AB - OBJECTIVE: Recent studies indicate acceptable survival rates in elderly patients treated surgically for acute type A aortic dissection (aTAAD). However, the impact of preoperative hemodynamic compromise or organ malperfusion on outcomes of such patients is still unclear. METHODS: In a retrospective study of 341 patients, 101 qualified as elderly (>=70 years old). Subjects were further grouped by clinical presentation, using the Penn classification. Univariate and multivariable analyses were conducted to identify variables reflecting in hospital and long-term mortality. RESULTS: Relative to younger subjects, elderly patients showed significantly higher rates of in-hospital mortality (24.8% vs. 14.6%, p = 0.025) and DeBakey type 2 dissections at presentation (40% vs. 18% p < 0.001), with significantly fewer presenting as Penn class Ab (p = 0.010). Penn class Ac was identified as an independent predictor of in-hospital mortality at all ages. Estimated long-term survival was poorer in the elderly (log rank p < 0.001); but in-hospital mortality, based on Penn classification, was similar for both age groups. Survival rates of Penn class Aa subjects at one, five, and 10 years were lower in elderly (vs. younger) patients (79 +/- 5.6% vs. 90 +/- 2.7%, 68 +/- 6.7% vs. 80 +/- 3.9%, and 39 +/- 10.3% vs. 75 +/- 4.6%, respectively; log rank p < 0.001). CONCLUSION: Overall in-hospital mortality is higher in elderly patients surgically treated for aTAAD. Malperfusion and/or hemodynamic instability at presentation confer a dismal prognosis, independent of patient age. PMID- 26354609 TI - The Double Jones Birefringence in Magneto-electric Medium. AB - In this paper, the Maxwell's equations for a tensorial magneto-electric (ME) medium are solved, which is an extension to the work on the uniaxial anisotropic nonmagnetic medium. The coefficients of the dielectric permittivity, magnetic permeability, and of the magneto-electric effect are considered as tensors. The polarization is shown lying in the plane of two perpendicular independent vectors, and the relationship for the transverse polarization is given. The propagation of an electromagnetic wave through a ME medium gives rise to double Jones birefringence. Besides, the condition for an independent phenomenon of D'yakonov surface wave in a magneto-isotropic but with magneto-electric medium is given, which is measurable experimentally when the incident angle is pi/4. Lastly, it is shown that the parameter for the magneto-electric effect plays a role in the damping of the wave. PMID- 26354611 TI - Local relapse of prostate cancer after primary definitive treatment: the management. AB - INTRODUCTION: Prostate cancer (PCa) is the most commonly diagnosed malignancy in men and the second leading cause of cancer-related death in industrialized countries. Even if the healing chances are very high after definitive treatment of localized disease, 20-30% of patients experience recurrence. EVIDENCE ACQUISITION: A review of the literature on the management of local recurrent prostate cancer was conducted using the Medline and Embase electronic databases. Search terms included "biochemical relapse", "PSA recurrence", "prostate cancer", "prostate cancer recurrence", "prostate salvage therapy", "radiorecurrent prostate cancer", "Re-HIFU", "post HIFU", "post cryoablation", "postradiation", and "postprostatectomy salvage". The search was restricted to English-language articles. The websites of guidelines organizations (EAU, AUA, NICE) were consulted in order to identify evidence-based practice guidelines. The present role of salvage prostatectomy and radiation therapy was studied and today's outcomes and tomorrow perspectives of salvage focal therapies as cryoablation and HIFU have been analyzed. EVIDENCE SYNTHESIS: Although the treatment landscape for patients with biochemical recurrence prostate cancer remains challenging, new research is helping to identify patient populations suitable for specific therapies. CONCLUSIONS: Further evaluation in prospective clinical trials will hopefully confirm the role of therapeutic options in clinical practice and the impact on the long-term survival. PMID- 26354610 TI - Type 2 diabetes - Tuberculosis co-morbidity is associated with diminished circulating levels of IL-20 subfamily of cytokines. AB - IL-20 subfamily of cytokines play an important role in both host defense mechanisms and glucose metabolism. Since, the interaction between tuberculosis (TB) and diabetes (DM) involves both of the above processes, we examined the association of IL-20 subfamily of cytokines in TB-DM co-morbidity. We examined circulating plasma cytokine levels in individuals with active TB with (PTB-DM) or without (PTB) diabetes and also those with latent TB with (LTB-DM) or without (LTB) diabetes. PTB-DM is characterized by diminished circulating levels of IL 19, IL-20, IL-22 and IL-24 but increased levels of IL-10. Similarly, LTB-DM was also characterized by diminished circulating levels of IL-10, IL-19, IL-20 and IL 24 but increased levels of IL-22. Moreover, there was a significant negative correlation of IL-10, IL-19, IL-20, IL-22 and IL-24 levels with hemoglobin A1C (HbA1c) levels in both PTB and/or LTB individuals. Finally, PTB is characterized by diminished levels of IL-19, IL-20, IL-22 and IL-24 in comparison to LTB individuals. Our data reveal that coincident diabetes in either PTB or LTB is characterized by decreased production of the IL-20 subfamily of cytokines and suggest that these cytokines might play an important role in pathogenesis or protection. PMID- 26354612 TI - Use of the International Consultation on Incontinence Questionnaire-Urinary Incontinence-Short Form (ICIQ-UI-SF) for an objective assessment of disability determination according to the Modified Katz Scale: a prospective longitudinal study. AB - BACKGROUND: The aim of this study was to demonstrate that the International Consultation on Incontinence Questionnaire-Urinary Incontinence-Short Form (ICIQ UI-SF) tool can be applied for a factual score determining urinary incontinence in the Katz-6 Scale, and it is effective to identify score 2 from score 3. METHODS: Functional capacity of 63 patients (14 M, 49 F aged from 70 to 99 years old) was evaluated with a Mini Mental State Examination (MMSE), Katz Index for Activities of Daily Living, and ICIQ-UI-SF questionnaire. Mean comparative analysis was performed. ICIQ-UI-SF scores were then entered as variables. These data observed in Katz continence item scored 2 and Katz continence item scored 3 were compared in a combined box-and-whisker and dot plot. Sensitivity and specificity of each variable were tested and results were evaluated using a receiver operating characteristic (ROC) curve. The best variable (ICIQ-UI-SF Score) was retained as a breach permitting to distinguish patients to be scored 2 or 3 over continence Katz item. RESULTS: Statistical analysis demonstrated significant difference between the sample of Katz continence item scored 2 and the sample of Katz continence item scored 3 over the ICIQ-UI-SF Score and the Katz global Score, but the difference was not significant concerning the MMSE Score. Using ROC analysis, we compared the discriminant power of the ICIQ-UI-SF Score for continence Katz item Score. Criterion values and coordinates of the ROC curve were studied and the ICIQ-UI-SF score of 13 was considered the best one. CONCLUSIONS: We demonstrated that the best variable (ICIQ-UI-SF Score) to retain as a breach permitting to distinguish patients to be scored 2 or 3 over continence Katz item is 13. PMID- 26354613 TI - Scoring surgical skill in robotic prostatectomy as adherence to the surgical plan: proposal for a new tool (ScAPSA). AB - BACKGROUND: The plethora of instruments (trifecta, pentafecta, etc.) used to evaluate the outcomes of robotic prostatectomy (RARP) has recently been subjected to criticism. In this paper, a novel approach called ScAPSA (Scoring Adherence to Prostatic Surgical Aims) is proposed to assess surgical proficiency, considering surgical success as perfect adherence to a correct surgical plan, and not related solely to clinical outcomes. METHODS: In order to define (and quantify) such adherence, and to evaluate both learning curves and surgeons' skill, a 20-point scoring system has been developed. The specific surgical plan (improved with predictive tools) is compared with pathological findings to identify any surgical errors. Adding data on postoperative complications, a score from 0 (better) to 20 (worst surgical result) can easily be calculated. Considering the number of reported cases needed to complete the RARP learning curve, we decided to analyze the first 25 consecutive single-surgeon RARPs. RESULTS: Testing ScAPSA on the first consecutive (initial learning curve) single-surgeon RARPs confirmed that this tool can faithfully describe and quantify both learning curves and surgical skill. CONCLUSIONS: ScAPSA may represent a useful novel tool, not only for describing RARP learning curves objectively, but also for determining and quantifying success rates, allowing surgeons to check intra-operative errors and monitor their own surgical proficiency. Further external validations are needed to confirm these results. PMID- 26354614 TI - The role of middle calyx puncture in percutaneous nephrolithotomy: relative factors and choice considerations. AB - Percutaneous nephrolithotomy (PCNL) is a well established procedure for management of renal calculi. It is generally believed that the access to the renal pelvic system via the desired calyx is the most crucial step during the whole procedure. The adequacy of the access directly influences the success and complication rates of PCNL. Traditionally, a lower pole access was routinely performed for less complication. Upper calices are also preferred for access in a given condition with large and complex calculi. However, the middle calices access is seldom selected. In aim to provide the reader some advantages of middle pole approach and a broaden horizon in determining the strategy of renal puncture, the present review describes the anatomical basis of the percutaneous tract. It provides a literature review of the success rate and efficiency of middle calyx access alone with the advantage of this approach, especially in dealing with large and complex stones. PMID- 26354615 TI - Minimizing radiation exposure during percutaneous nephrolithotomy. AB - Given the recent trends in growing per capita radiation dose from medical sources, there have been increasing concerns over patient radiation exposure. Patients with kidney stones undergoing percutaneous nephrolithotomy (PNL) are at particular risk for high radiation exposure. There exist several risk factors for increased radiation exposure during PNL which include high Body Mass Index, multiple access tracts, and increased stone burden. We herein review recent trends in radiation exposure, radiation exposure during PNL to both patients and urologists, and various approaches to reduce radiation exposure. We discuss incorporating the principles of As Low As reasonably Achievable (ALARA) into clinical practice and review imaging techniques such as ultrasound and air contrast to guide PNL access. Alternative surgical techniques and approaches to reducing radiation exposure, including retrograde intra-renal surgery, retrograde nephrostomy, endoscopic-guided PNL, and minimally invasive PNL, are also highlighted. It is important for urologists to be aware of these concepts and techniques when treating stone patients with PNL. The discussions outlined will assist urologists in providing patient counseling and high quality of care. PMID- 26354616 TI - The role of robotic surgery in the treatment of urolithiasis. AB - Renal stones in the modern era are most commonly treated with minimally invasive techniques and using endourological procedures. However, for more complex cases, there is renewed interest in exploring laparoscopic or robotic techniques that can offer patients significant benefits over otherwise multiple endourologic or open surgical intervention. In clinical circumstances with anomalous anatomy, indication for concomitant reconstruction, or previously failed endourological intervention, robotic and laparoscopic approaches may offer suitable, if not more effective, treatment options. PMID- 26354617 TI - 50th Anniversary Perspective on Volume 1: Trummer MJ. Experimental Transplantation of the Lung. Ann Thorac Surg 1965;1:203-19. PMID- 26354618 TI - 50th Anniversary Landmark Commentary on Carpentier A, Relland J, Deloche A, et al. Conservative management of the prolapsed mitral valve. Ann Thorac Surg 1978;26:294-302. PMID- 26354619 TI - 50th Anniversary Landmark Commentary on Adkins PC, Orthner HF. The Society of Thoracic Surgeons Manpower Survey for 1976: a summary. Ann Thorac Surg 1979;28:407-12. PMID- 26354620 TI - 50th Anniversary Landmark Commentary on Jensik RJ, Faber LP, Kittle CF. Segmental resection for bronchogenic carcinoma. Ann Thorac Surg 1979;28:475-83. PMID- 26354621 TI - Invited Commentary. PMID- 26354622 TI - Invited Commentary. PMID- 26354623 TI - Invited Commentary. PMID- 26354624 TI - Invited Commentary. PMID- 26354625 TI - Invited Commentary. PMID- 26354626 TI - Invited Commentary. PMID- 26354627 TI - Invited Commentary. PMID- 26354628 TI - Invited Commentary. PMID- 26354629 TI - Invited Commentary. PMID- 26354630 TI - Invited Commentary. PMID- 26354631 TI - Invited Commentary. PMID- 26354632 TI - Thymoma-Associated Graft-Versus-Host-Like Disease With Skin Manifestations Improved by Complete Resection of Thymoma. AB - A 69-year-old woman with refractory skin eruptions, which had first appeared 3 years previously, was examined, and an anterior mediastinal tumor was detected. The tumor was resected, and a diagnosis of type B2 thymoma, stage III disease (according to the World Health Organization classification), was made. Retrospectively, histologic findings of the skin before the operation were consistent with graft-versus-host disease. The final diagnosis of her skin lesions was thymoma-associated graft-versus-host-like disease. The skin lesions improved gradually during the 1-month period after resection with only a topical steroid, and further improvement was seen at 3 months. PMID- 26354633 TI - Exophytic Atheroma Mimicking Papillary Fibroelastoma Adjacent to the Aortic Valve. AB - Follow-up echocardiography in a 69-year-old man with alcoholic cardiomyopathy showed a mass above the aortic valve near the left coronary ostium. Transesophageal echocardiography and computed tomography suggested a papillary fibroelastoma with a high risk of embolism. At operation we found an exophytic atheroma adjacent to the left coronary artery orifice. The atheroma was removed, and the patient made an uneventful recovery. We describe this very rare case of an exophytic atheroma mimicking a papillary fibroelastoma situated at the left coronary orifice. PMID- 26354634 TI - Minimally Invasive Coronary Artery Bypass Grating Using Bilateral In Situ Internal Thoracic Arteries. AB - When performing minimally invasive coronary artery bypass grafting (MICS CABG), it is difficult to access the right internal thoracic artery (ITA) under direct vision. We successfully performed off-pump MICS CABG using the bilateral in situ ITAs through a 8-cm left thoracotomy under direct vision for a 76-year-old man. His postoperative course was uneventful and all the grafts were patent. This novel, minimally invasive approach safely preserves the sternum and delivers the benefits of bilateral in situ ITA grafting, providing an alternative to conventional CABG and off-pump CABG. PMID- 26354635 TI - Arterial Switch Operation in Single Coronary Ostium With Intramural Course: Subclavian Artery Patch Angioplasty. AB - This report describes a neonatal arterial switch operation in a transposition of the great arteries with single ostium and intramural course coronary pattern. The technique proposed is based on the creation of two coronary neoostia by incising the left coronary intramural course and splitting the common button followed by a patch enlargement of left coronary button using the left subclavian artery. PMID- 26354636 TI - Coronary Vasospasm as an Unexpected Cause of Intraoperative Hemodynamic Instability and Cardiac Arrest. AB - We present a case of intraoperative coronary artery vasospasm during thoracic surgery causing profound hemodynamic instability. A 68-year-old man undergoing completion right pneumonectomy exhibited intraoperative widespread ST elevation with associated hypotension. Transesophageal echocardiography performed by the anesthetist revealed hypokinetic apical and lateral walls, prompting transportation to the catheterization laboratory, with angiography demonstrating widespread coronary artery spasm. Intracoronary nitroglycerin relieved the vasospasm; however, heparin administration caused significant postoperative bleeding, resulting in cardiac arrest requiring resuscitation and return to the operating room. He ultimately recovered and was discharged to a rehabilitation facility 3 weeks later. PMID- 26354637 TI - Less-Invasive Endovascular Treatment of Arch Aneurysm With Aberrant Right Subclavian Artery. AB - We report a patient with an arch aneurysm with an aberrant right subclavian artery who underwent successful endovascular treatment with the chimney technique and bilateral carotid artery-to-subclavian artery bypasses. We used a chimney graft in the left carotid artery to preserve its flow. The bilateral carotid-to subclavian artery bypasses preserved perfusion of the bilateral vertebral arteries. A thoracic stent graft was subsequently deployed in the aortic arch over the chimney graft of the left carotid artery. There have been few reports about less-invasive treatment for arch aneurysm with aberrant right subclavian artery. This technique was an effective strategy to avoid a high-risk open operation. PMID- 26354638 TI - Combined Treatment of an Aortoesophageal Fistula After Aortoplasty for Aortic Stenosis. AB - The aortoesophageal fistula secondary to the rupture of an aneurysm is a rare entity that usually has a fatal outcome. We present the case of a young patient with an aortoesophageal fistula secondary to a thoracic aortic aneurysm successfully treated with a combination of endoscopic and surgical techniques. PMID- 26354639 TI - Chest Blunt Trauma: An Uncommon Cause of Aortic Stentless Bioprosthesis Dysfunction. AB - Acute leaflet rupture occurred in a Freedom Solo (Sorin Group, Milan, Italy) pericardial stentless aortic bioprosthesis after chest blunt trauma 8 years after valve replacement. Intraoperative findings revealed an acute tear of the right cusp at the level of the structural suture line. Pericardial leaflets were not degenerated at histologic analysis. Reoperation was easy, with simple removal of the prosthetic cusps, and a sutureless Perceval (Sorin Group) bioprosthesis was successfully implanted. This is the first reported case of an acute rupture of a stentless aortic bioprosthesis after a chest blunt trauma and the first histologic analysis of an 8-year-old Freedom Solo. PMID- 26354640 TI - Poor Left Ventricular Performance in a Child With Coronary Sinus Stenosis: Successful Surgical Repair. AB - Atresia or stenosis of the coronary sinus is a rare congenital defect that can cause marked clinical manifestations, depending on the presence of concomitant anomalies securing adequate coronary venous outflow. We describe a 4.5-year-old boy admitted to the clinic with signs of congestive heart failure (left ventricular ejection fraction, 29%). His condition had deteriorated during the previous 4 months. The examination revealed stenosis of the coronary sinus ostium, coronary sinus-to-left atrium fistula, mitral regurgitation of the second grade, and moderate pulmonary hypertension. The surgical intervention consisted of enlargement and plastic reconstruction of the coronary sinus as well as closure of the coronary sinus-to-left atrium fistula. The hospital period was uneventful. The left ventricular ejection fraction at discharge increased up to 50%. PMID- 26354641 TI - Hepatoesophageal Fistula After Radiofrequency Ablation for Hepatic Metastasis. AB - Although surgical resection remains the treatment of choice for hepatic tumors, radiofrequency ablation has emerged as a reliable alternative. Radiofrequency ablation is both less invasive and can be repeated after short intervals in cases of multiple lesions that cannot be treated with surgical resection. Liver abscess, which may progress to internal enteral fistula, is the most common complication of radiofrequency ablation. Here we present the first case report in the literature of a rare complication of hepatoesophageal fistula after radiofrequency ablation for colon cancer with liver metastasis. This case was well managed with percutaneous abscess drainage, antibiotics, and separation of the hepatoesophageal fistula using an esophageal stent. PMID- 26354642 TI - Intraventricular Bronchogenic Cyst: A Rare Congenital Anomaly. AB - Intracardiac bronchogenic cyst is a rare congenital anomaly. This tumor is usually found in the mediastinum (12% to 18% of all primary mediastinal masses) or in the lung parenchyma (15% to 30% of them). Although rare, it should be included in the differential diagnosis of intracardiac tumors. Complete resection is recommended for diagnosis and for therapeutic reasons. We present here a rare case of an intracardiac left ventricular bronchogenic cyst in an asymptomatic 41 year-old woman. PMID- 26354643 TI - Prosthetic Pulmonary Valve Stenosis: A Different Way to Solve the Problem. AB - To avoid a third major cardiovascular surgery in an 84-year-old man, a Melody Transcatheter Pulmonary Valve was implanted in a functionally stenotic bioprosthesis in the pulmonary position. The intervention was free of complications with good results. PMID- 26354644 TI - Lymphangioleiomyomatosis in a Male. AB - We report a 17-year-old male with a histopathologic diagnosis of lymphangioleiomyomatosis after surgery for a pneumothorax. In general, lymphangioleiomyomatosis has been considered a female-specific disease. However, there are a few lymphangioleiomyomatosis cases reported in males, and our patient is the youngest case reported. Spontaneous pneumothorax occurs most commonly in males in their late teens and early twenties. Histopathologic diagnosis cannot always be performed in young males with pneumothorax. However, simple diagnosis should be avoided, and lymphangioleiomyomatosis should be considered as an underlying disease. This remarkable case provides new and valuable clinical insights into young male pneumothorax. PMID- 26354645 TI - Large Endobronchial Hamartoma Successfully Resected by Snare Through Flexible Bronchoscopy. AB - Benign pulmonary tumors are rare, composing less than 1% of pulmonary tumors; of these, hamartomas are the most common. Endobronchial hamartomas are rarer still, composing 1.4% of all pulmonary hamartomas. As therapeutic bronchoscopy has improved, it has replaced conventional operations for resection of endobronchial benign tumors, although there are limitations to the procedure in the case of large tumors causing complete obstruction. The present report describes a case of a large endobronchial hamartoma inducing total lung atelectasis, which was successfully resected using an electrosurgical snare through flexible bronchoscopy. This could be a useful option in select endobronchial tumors. PMID- 26354646 TI - Multifocal Endobronchial Fibromas Presenting as Unilobar Emphysema. AB - Tracheobronchial fibromas are very rare, locally-invasive tumors of the airways. Fewer than 30 cases have been reported within the English-speaking literature. Historically, these neoplasms have been diagnosed as isolated endobronchial masses, with affected patients presenting with wheezing, cough, stridor, hemoptysis, dyspnea, or pneumonia. We report the case of 39-year-old man with multiple, synchronous endobronchial fibromas causing unilobar emphysema. A computed tomographic scan and bronchoscopy with biopsy were performed preoperatively to diagnose these lesions in the orifices of the anterior segment and the lingula within the left upper lobe. The patient underwent successful video-assisted left upper lobectomy, without recurrence at 3 years. This is the first report of a synchronous presentation of multiple pulmonary endobronchial fibromas within the same patient and the first report of endobronchial fibroma presenting as unilobar air trapping. Recognition of the unusual presentation of this uncommon pathology can lead to timely intervention. PMID- 26354647 TI - A Nearly Missed Catastrophic Aortic Injury After Reduction of a Thoracic Spine Fracture Managed by Prompt Endovascular Treatment. PMID- 26354648 TI - Unilateral Absence of the Right Pulmonary Artery Accompanied by Right Lung Cancer. PMID- 26354649 TI - Angiosarcoma Mimicking an Infected Pseudoaneurysm After Graft Replacement. PMID- 26354650 TI - Single-Port Mediastinoscopic Lymphadenectomy Along the Left Recurrent Laryngeal Nerve. AB - We herein describe a single-port mediastinoscopic method for upper mediastinal dissection in esophageal cancer surgery. After the left cervical incision and lymphadenectomy, a Lap-Protector (Hakko, Tokyo, Japan) was inserted into the wound and an EZ Access port (Hakko) was attached. Esophageal mobilization with en bloc lymphadenectomy along the left recurrent laryngeal nerve was then performed using a port-in-port technique with conventional flexible laparoscopy. Carbon dioxide insufflation expanded the intramediastinal space, and minute structures in the deep mediastinum around the aortic arch, such as nerves, bronchial arteries, and lymphatic vessels, were clearly visualized, allowing lymphadenectomy to be safely and carefully performed along the nerve. PMID- 26354651 TI - Pressurized Cadaver Model in Cardiothoracic Surgical Simulation. AB - Simulation is increasingly recognized as an integral aspect of thoracic surgery education. A number of simulators have been introduced to teach component cardiothoracic skills; however, no good model exists for numerous essential skills including redo sternotomy and internal mammary artery takedown. These procedures are often relegated to thoracic surgery residents but have significant negative implications if performed incorrectly. Fresh tissue dissection is recognized as the gold standard for surgical simulation, but the lack of circulating blood volume limits surgical realism. Our aim is to describe the technique of the pressurized cadaver for use in cardiothoracic surgical procedures, focusing on internal mammary artery takedown. PMID- 26354652 TI - A Novel Surgical Technique for Repair of Congenitally Corrected Transposition of the Great Arteries With Atrioventricular Septal Defect: Avoiding Damage to the Conduction System. AB - We present a description of the surgical repair of the unusual anatomy of congenitally corrected transposition of the great arteries (S, L, L) and balanced atrioventricular septal defect. This anatomy not only presents a dilemma regarding palliation versus anatomic correction, but also regarding the approach to the conduction tissue during surgical repair. PMID- 26354653 TI - Two-Strip Technique to Repair Common Atrioventricular Valve Regurgitation in Single-Ventricle Palliation. AB - A common atrioventricular valve (CAVV) presents a challenge in single-ventricle palliation (SVP) because of its propensity to leak, with CAVV regurgitation being an important risk factor for repeated operation and mortality. We propose a new technique of CAVV repair in the context of SVP. The method uses the techniques of complete repair of antrioventricular septal defect while maintaining free communication at atrial and ventricular levels necessary for single-ventricle physiology. PMID- 26354654 TI - Improving the Exposure of the Left Hilum for Lung Transplantation: The Value of a Simple Pericardial Stitch. PMID- 26354655 TI - Reply: To PMID 25282230. PMID- 26354656 TI - Reply: To PMID 25534527. PMID- 26354657 TI - Meta-Analysis of Different Procedures: The Importance of Recognizing the Spectrum of Pleurectomy/Decortication Techniques. PMID- 26354658 TI - Reply: To PMID 25662440. PMID- 26354659 TI - Can Septic Condition or Stroke Impact on the Procalcitonin Level Along With Mesenteric Ischemia After Cardiac Surgery? PMID- 26354660 TI - Reply: To PMID 25497075. PMID- 26354661 TI - More Data Are Needed to Determine an Association Between Transfusions and Coronary Artery Bypass Graft Occlusion. PMID- 26354662 TI - Type A Aortic Dissection: The Controversy of the Root Replacement. PMID- 26354663 TI - Reply: To PMID 25282163. PMID- 26354664 TI - Marking Techniques for Pulmonary GGO's. PMID- 26354665 TI - Aortic Coarctation Diagnosed During Pregnancy in a Woman With Repaired Tetralogy of Fallot. AB - Aortic coarctation is thought to be a rare condition in patients with tetralogy of Fallot. We report the case of a 26 year old woman presenting with systemic hypertension at 17 weeks of pregnancy after repair of tetralogy of Fallot in childhood. Echocardiography and magnetic resonance imaging revealed right aortic arch with severe isthmic coarctation. Her blood pressure was controlled medically during the rest of her pregnancy, and delivery was uneventful. Successful transcatheter placement of a covered stent at the level of the coarctation was performed after delivery. To our knowledge, this is the first reported case of aortic coarctation diagnosed in an adult patient late after repair of tetralogy of Fallot. PMID- 26354666 TI - Mediastinal Fibrosis of the Pulmonary Artery Secondary to Tuberculosis. AB - Mediastinal fibrosis is an uncommon disease involving the esophagus, respiratory tract, and great vessels. We report a man who presented with dyspnea on exertion. Computed tomography of the chest demonstrated granulomatous disease with dense calcifications leading to severe stenosis of the main pulmonary artery (PA) and narrowing of the superior vena cava. The results of tuberculosis (TB) interferon gamma release assay and TB-polymerase chain reaction were positive for Mycobacterium tuberculosis. The patient received 2 weeks of treatment for latent TB before undergoing resection of fibrotic tissue and replacement of the main and branch PAs using a homograft. PMID- 26354667 TI - Cerebral Hyperperfusion Syndrome After Surgical Repair of Congenital Supravalvular Aortic Stenosis. AB - Although cerebral hyperperfusion syndrome is rarely encountered, this condition can be serious after procedures that increase cerebral blood flow; most reports are related to carotid revascularization. Sharp cerebral hemodynamic changes, along with impaired cerebrovascular autoregulation, are the main mechanisms contributing to this syndrome. We report a patient who underwent surgical correction for congenital supravalvular aortic stenosis and presented with postoperative hypertension, headache, impairment of consciousness, and cerebral edema 2 days after operation. He recovered well when the blood pressure declined and the brain edema subsided. Cerebral hyperperfusion syndrome was considered, and this uncommon neurologic complication of cardiac operations is discussed. PMID- 26354668 TI - Expanding Applicability of Total Artificial Heart Therapy: The 50-cc SynCardia Total Artificial Heart. AB - The 50-cc SynCardia total artificial heart is designed to facilitate orthotopic replacement of the native ventricles in patients with a body surface area below 1.7 m(2) in need of long-term circulatory support as a result of end-stage biventricular heart failure. We describe the implementation of this technology in a female patient with irreversible cardiogenic shock on the grounds of acute myocardial infarction and chronic ischemic cardiomyopathy. PMID- 26354669 TI - A Simple, Effective, and Inexpensive Technique for Exposure of Papillary Muscles in Minimally Invasive Mitral Valve Repair: Wakka Technique. AB - Obtaining excellent exposure of the papillary muscles is challenging in minimally invasive mitral valve repair. We have developed a simple and effective technique using a sterile paper ruler. The ruler is cut to the proper length (8 to 12 cm) depending on the valve size, then rolled and sutured. The rolled ruler, 7 to 11 cm in circumference, is placed inside the mitral leaflets. This technique provides excellent exposure of the papillary muscles without damaging the leaflets and prevents chordal injury during artificial chordal implantation. PMID- 26354670 TI - A Surgical Integration Technique for Right-Sided and Left-Sided Superior Venae Cavae. AB - The treatment of some subsets of patients having both right-sided superior vena cava (SVC) and left-sided SVC may be very challenging. We performed the SVC integration (SVCI) technique with end-to-side anastomoses between the two SVCs on 4 such patients (age, 5 to 11 months; body weight, 5.4 to 10.2 kg) with excellent outcomes. In 2 patients, we performed intrapulmonary artery septation with SVCI; in 1 patient, pulmonary artery sling repair with SVCI; and in 1 patient with supramitral stenosis related to persistent left-sided SVC, repeated Blalock Taussig shunt (BTS) with SVCI. Our SVCI technique is very useful in specific cases (eg, in candidates for the Fontan procedure. PMID- 26354671 TI - Within-subject consistency and between-subject variability in Bayesian reasoning strategies. AB - It is well known that people tend to perform poorly when asked to determine a posterior probability on the basis of a base rate, true positive rate, and false positive rate. The present experiments assessed the extent to which individual participants nevertheless adopt consistent strategies in these Bayesian reasoning problems, and investigated the nature of these strategies. In two experiments, one laboratory-based and one internet-based, each participant completed 36 problems with factorially manipulated probabilities. Many participants applied consistent strategies involving use of only one of the three probabilities provided in the problem, or additive combination of two of the probabilities. There was, however, substantial variability across participants in which probabilities were taken into account. In the laboratory experiment, participants' eye movements were tracked as they read the problems. There was evidence of a relationship between information use and attention to a source of information. Participants' self-assessments of their performance, however, revealed little confidence that the strategies they applied were actually correct. These results suggest that the hypothesis of base rate neglect actually underestimates people's difficulty with Bayesian reasoning, but also suggest that participants are aware of their ignorance. PMID- 26354672 TI - Re: Reconsideration of the clinical and histopathological significance of angiogenesis in prostate cancer: Usefulness and limitations of microvessel density measurement. PMID- 26354673 TI - Cluster of Imported Vivax Malaria in Travelers Returning From Peru. AB - We report a cluster of imported vivax malaria in three of five Chilean travelers returning from Peru in March 2015. The cluster highlights the high risk of malaria in the Loreto region in northern Peru, which includes popular destinations for international nature and adventure tourism. According to local surveillance data, Plasmodium vivax is predominating, but Plasmodium falciparum is also present, and the incidence of both species has increased during recent years. Travelers visiting this region should be counseled about the prevention of malaria and the options for chemoprophylaxis. PMID- 26354674 TI - The outcome of infliximab dose doubling in 157 patients with ulcerative colitis after loss of response to infliximab. AB - BACKGROUND: Optimising infliximab therapy is recommended in inflammatory bowel disease (IBD) patients who lose response to infliximab; however, there are no data on the outcome of ulcerative colitis (UC) patients after doubling the dose. AIM: To determine the efficacy and safety of infliximab dose doubling in UC patients with a loss of response to infliximab. METHODS: From January 2006 to May 2013, we retrospectively reviewed the outcome of the consecutive UC patients who were treated with infliximab dose doubling (10 mg/kg) for loss of response in four French academic centres. The clinical response and remission were assessed. A composite event-free survival analysis was performed using the log-rank test and the Cox model. RESULTS: One hundred and fifty-seven patients [84 males; median age 37. 6 (IQR 28.2-49.4) years] were included. The median follow-up after infliximab dose doubling was 1.8 (1.0-3.1) years. At weeks 8 and 24, 55% and 43% of the patients achieved a clinical response respectively. The probabilities of the event-free survival were 71%, 61% and 55% at 6 months, 1 year and 2 years respectively. In the multivariate analysis, the predictors of infliximab dose doubling failure were the absence of the introduction of an immunomodulator concomitantly to dose doubling, a partial Ulcerative Colitis Disease Activity Index >6, a C-reactive protein level >10 mg/L, a leucocyte count >8000/mm(3) and a haemoglobin level <12.5 g/dL. Adverse events were reported in 12 patients (8%). CONCLUSIONS: Infliximab dose doubling led to short- and long-term event-free survival in UC patients, who had a loss of response to infliximab, in greater than 50% of the cases. The benefits of such a strategy were significantly improved by adding a concomitant immunomodulator. PMID- 26354676 TI - Pulmonary manifestations in a group of patients with Behcet's disease. AB - AIM: In this study we investigated the frequency and characteristics of pulmonary manifestations in a group of patients with Behcet's disease (BD) who were admitted to Cairo University Hospital. METHODS: Fifteen patients were included in our study, 14 men (93.3%) and one woman (6.66%).Their mean age was 30.06 +/- 9.8 years and the mean age of onset of BD was 23.7 +/- 5.54 years. All patients were subjected to full history taking, clinical examination, plain chest X-ray and helical computed tomography (CT) study of the chest. RESULTS: Pulmonary involvements were detected in 11 patients with BD, 73.3% of cases: 10 men (90.9%) and one woman (9.09%).Their mean age was 28.8 +/- 8.07, the mean age of onset of BD was 23.2 +/- 5.59 years and the mean disease duration until lung manifestations appear was 3.7 +/- 4.8 years. The main pulmonary and constitutional symptoms in these 11 patients were as follows: dyspnea 81.8%, cough 63.6%, weight loss 63.6%, chest tightness 54.5%, hemoptysis 45%, massive hemoptysis 27.2%, fever 36.3% and expectoration 36.3. Analysis of both vascular and parenchymal lung lesions in helical CT scan in the 11 patients with BD were as follows: pulmonary artery aneurysm (PAA) occurred in 5/11 patients (45.4%), pulmonary nodules occurred in 3/11 patients (27.2%), pleural effusion occurred in 3/11 patients (27.2%), pulmonary embolism and infarction occurred in 1/11 patients (9.09%) and pneumonitis occurred in 1/11 patients (9.09%). CONCLUSION: The higher frequency of pulmonary manifestations in our patients (73.3%) and the higher frequency of PAA (33.3%) could be related to the fact that this study was conducted on a group of patients who were admitted to the hospital with more severe illnesses. PMID- 26354675 TI - RIFLE classification in geriatric patients with acute kidney injury in the intensive care unit. AB - BACKGROUND: The RIFLE classification is widely used to assess the severity of acute kidney injury (AKI), but its application to geriatric AKI patients complicated by medical problems has not been reported. METHODS: We investigated 256 geriatric patients (>=65 years old; mean age, 74.4 +/- 6.3 years) who developed AKI in the intensive care unit (ICU) according to the RIFLE classification. Etiologic, clinical, and prognostic variables were analyzed. RESULTS: They were categorized into RIFLE-R (n = 53), RIFLE-I (n = 102), and RIFLE-F (n = 101) groups. The overall in-hospital mortality was 39.8 %. There were no significant differences in RIFLE category between survivors and non survivors. Survivors had significantly less needs for a ventilator and vasopressor, and lower number of failing organs. Survivors had higher systolic blood pressure, hemoglobin level, and serum albumin levels. We performed a logistic regression analysis to identify the independent predictors of in hospital mortality. In a univariate analysis, hypertension, chronic kidney disease, RIFLE classification, number of failing organs, need for a ventilator and vasopressor, systolic blood pressure, hemoglobin level, and serum albumin levels were identified as prognostic factors of in-hospital mortality. However, in a multivariate analysis, hypertension, chronic kidney disease, number of failing organs, and serum albumin levels were independent risk factors, with no significant difference for in-hospital mortality with the RIFLE classification. CONCLUSION: The RIFLE classification might not be associated with mortality in geriatric AKI patients in the ICU. In geriatric patients with AKI, various factors besides severity of AKI should be considered to predict mortality. PMID- 26354677 TI - Kick with the finger: symbolic actions shape motor cortex excitability. AB - A large body of research indicates that observing actions made by others is associated with corresponding motor facilitation of the observer's corticospinal system. However, it is still controversial whether this matching mechanism strictly reflects the kinematics of the observed action or its meaning. To test this issue, motor evoked potentials induced by single-pulse transcranial magnetic stimulation were recorded from hand and leg muscles while participants observed a symbolic action carried out with the index finger, but classically performed with the leg (i.e., a soccer penalty kick). A control condition in which participants observed a similar (but not symbolic) hand movement was also included. Results showed that motor facilitation occurs both in the observer's hand (first dorsal interosseous) and leg (quadriceps femoris) muscles. The present study provides evidence that both the kinematics and the symbolic value of an observed action are able to modulate motor cortex excitability. The human motor system is thus not only involved in mirroring observed actions but is also finely tuned to their symbolic value. PMID- 26354678 TI - Safety of zidovudine dose reduction in treatment-naive HIV infected patients. A randomized controlled study (MiniZID). AB - BACKGROUND: Since September 2014, zidovudine (ZDV)-based therapy for HIV has been the preferred second-line WHO regimen in Cameroon, but its use is limited by the risk of anaemia at standard dosage. We assessed the safety of a reduced vs. standard dose of ZDV to decrease the risk of anaemia in treatment-naive, HIV infected individuals. METHODS: In a prospective, randomized, open-label trial in an HIV clinic in Cameroon, 142 eligible adults (CD4 count < 350 cells/MUL) were randomized to receive 24 weeks of a regimen comprising lamivudine plus nevirapine with either a reduced (400 mg) or standard dose (600 mg) of ZDV. The primary endpoint was the proportion of participants with new/worsening anaemia. RESULTS: Median age was 35 years; 58.5% were women; median body mass index was 23.2 kg/m(2) . At baseline, median haemoglobin was 11.6 g/dL, median CD4 cell count was 163 cells/MUL, and median plasma HIV-1 RNA load was 5.4 log10 copies/mL. The proportion of participants with new/worsening anaemia was 37.5% (400 mg ZDV) and 32.9% (600 mg ZDV) (P = 0.563). Ten patients with severe anaemia required a switch from ZDV to tenofovir (11.4% in standard-dose arm vs. 2.8% in low-dose arm; P = 0.054). At 24 weeks, there was no significant difference between treatment groups, including median CD4 T-cell count increases. CONCLUSIONS: No significant difference was observed in the overall rate of anaemia between HIV infected individuals starting a ZDV-based treatment according to a standard- or reduced-dose regimen. Severe anaemia and treatment switches related to study drug, however, were more frequent with 600 mg than 400 mg ZDV. PMID- 26354679 TI - Comparison of non-linear models to describe the lactation curves for milk yield and composition in buffaloes (Bubalus bubalis). AB - In order to describe the lactation curves of milk yield (MY) and composition in buffaloes, seven non-linear mathematical equations (Wood, Dhanoa, Sikka, Nelder, Brody, Dijkstra and Rook) were used. Data were 116,117 test-day records for MY, fat (FP) and protein (PP) percentages of milk from the first three lactations of buffaloes which were collected from 893 herds in the period from 1992 to 2012 by the Animal Breeding Center of Iran. Each model was fitted to monthly production records of dairy buffaloes using the NLIN and MODEL procedures in SAS and the parameters were estimated. The models were tested for goodness of fit using adjusted coefficient of determination (Radj(2)), root means square error (RMSE), Durbin-Watson statistic and Akaike's information criterion (AIC). The Dijkstra model provided the best fit of MY and PP of milk for the first three parities of buffaloes due to the lower values of RMSE and AIC than other models. For the first-parity buffaloes, Sikka and Brody models provided the best fit of FP, but for the second- and third-parity buffaloes, Sikka model and Brody equation provided the best fit of lactation curve for FP, respectively. The results of this study showed that the Wood and Dhanoa equations were able to estimate the time to the peak MY more accurately than the other equations. In addition, Nelder and Dijkstra equations were able to estimate the peak time at second and third parities more accurately than other equations, respectively. Brody function provided more accurate predictions of peak MY over the first three parities of buffaloes. There was generally a positive relationship between 305-day MY and persistency measures and also between peak yield and 305-day MY, calculated by different models, within each lactation in the current study. Overall, evaluation of the different equations used in the current study indicated the potential of the non-linear models for fitting monthly productive records of buffaloes. PMID- 26354681 TI - Large-scale models of signal propagation in human cells derived from discovery phosphoproteomic data. AB - Mass spectrometry is widely used to probe the proteome and its modifications in an untargeted manner, with unrivalled coverage. Applied to phosphoproteomics, it has tremendous potential to interrogate phospho-signalling and its therapeutic implications. However, this task is complicated by issues of undersampling of the phosphoproteome and challenges stemming from its high-content but low-sample throughput nature. Hence, methods using such data to reconstruct signalling networks have been limited to restricted data sets and insights (for example, groups of kinases likely to be active in a sample). We propose a new method to handle high-content discovery phosphoproteomics data on perturbation by putting it in the context of kinase/phosphatase-substrate knowledge, from which we derive and train logic models. We show, on a data set obtained through perturbations of cancer cells with small-molecule inhibitors, that this method can study the targets and effects of kinase inhibitors, and reconcile insights obtained from multiple data sets, a common issue with these data. PMID- 26354680 TI - High-efficiency reprogramming of fibroblasts into cardiomyocytes requires suppression of pro-fibrotic signalling. AB - Direct reprogramming of fibroblasts into cardiomyocytes by forced expression of cardiomyogenic factors, GMT (GATA4, Mef2C, Tbx5) or GHMT (GATA4, Hand2, Mef2C, Tbx5), has recently been demonstrated, suggesting a novel therapeutic strategy for cardiac repair. However, current approaches are inefficient. Here we demonstrate that pro-fibrotic signalling potently antagonizes cardiac reprogramming. Remarkably, inhibition of pro-fibrotic signalling using small molecules that target the transforming growth factor-beta or Rho-associated kinase pathways converts embryonic fibroblasts into functional cardiomyocyte-like cells, with the efficiency up to 60%. Conversely, overactivation of these pro fibrotic signalling networks attenuates cardiac reprogramming. Furthermore, inhibition of pro-fibrotic signalling dramatically enhances the kinetics of cardiac reprogramming, with spontaneously contracting cardiomyocytes emerging in less than 2 weeks, as opposed to 4 weeks with GHMT alone. These findings provide new insights into the molecular mechanisms underlying cardiac conversion of fibroblasts and would enhance efforts to generate cardiomyocytes for clinical applications. PMID- 26354683 TI - Comparison of three prognostic scoring systems in a series of 146 cases of chronic myelomonocytic leukemia (CMML): MD Anderson prognostic score (MDAPS), CMML-specific prognostic scoring system (CPSS) and Mayo prognostic model. A detailed review of prognostic factors in CMML. AB - Although specific prognostic models for chronic myelomonocytic leukemia (CMML) exist, few are based on large series of patients. MD Anderson prognostic score (MDAPS) has been the most useful for CMML risk assessment. Due to recent emergence of CMML-specific prognostic scoring system (CPSS) and Mayo prognostic model, we compared the three scores. One hundred forty-six CMML patients diagnosed between 1998 and 2014 were retrospectively analyzed. Univariate analysis was performed to assess prognostic impact on overall survival (OS) and leukemia-free survival (LFS) of the variables composing the scores and all items showed prognostic value on OS with the exception of the presence of circulating immature myeloid cells. Regarding LFS, only CPSS variables, bone marrow blast >=10% and an absolute monocyte count >10*109/L had an impact. When the scores were applied, all showed an impact on OS and retained their significance in multivariate analysis. By using ROC curves and C-index, CPSS showed a slightly better predictive value for mortality and leukemia transformation. Variables composing the three indexes were compared in multivariate analysis and only CPSS parameters and platelets<100*109/L retained their significance. Based on these findings, by adding platelet count to CPSS, a new score was implemented (CPSS-P) showing the best risk prediction capability in our series. This study reinforces the validity of the tested scores. PMID- 26354684 TI - Risk of Coronary Obstruction in Transcatheter Aortic Valve Replacement. PMID- 26354682 TI - Hypoxia Promotes Synergy between Mitomycin C and Bortezomib through a Coordinated Process of Bcl-xL Phosphorylation and Mitochondrial Translocation of p53. AB - Colorectal peritoneal carcinomatosis (CPC) exhibits severe tumor hypoxia, leading to drug resistance and disease aggressiveness. This study demonstrates that the combination of the chemotherapeutic agent mitomycin C with the proteasome inhibitor bortezomib induced synergistic cytotoxicity and apoptosis, which was even more effective under hypoxia in colorectal cancer cells. The combination of mitomycin C and bortezomib at sublethal doses induced activation of c-Jun NH2 terminal kinase and p38 mitogen-activated protein kinase and resulted in Bcl-xL phosphorylation at Serine 62, leading to dissociation of Bcl-xL from proapoptotic Bak. Interestingly, the intracellular level of p53 became elevated and p53 translocated to the mitochondria during the combinatorial treatment, in particular under hypoxia. The coordinated action of Bcl-xL phosphorylation and p53 translocation to the mitochondria resulted in conformational activation of Bak oligomerization, facilitating cytochrome c release and apoptosis induction. In addition, the combinatorial treatment with mitomycin C and bortezomib significantly inhibited intraperitoneal tumor growth in LS174T cells and increased apoptosis, especially under hypoxic conditions in vivo. This study provides a preclinical rationale for the use of combination therapies for CPC patients. IMPLICATIONS: The combination of a chemotherapy agent and proteasome inhibitor at sublethal doses induced synergistic apoptosis, in particular under hypoxia, in vitro and in vivo through coordinated action of Bcl-xL and p53 on Bak activation. PMID- 26354685 TI - Hemodynamic complications during transcatheter MitraClip repair in presence of congenital atrial septal defect. AB - Transcatheter edge-to-edge mitral valve repair with MitraClip System (Abbott Vascular, Menlo Park, CA) needs a trans-septal access for positioning the 22-Fr guiding catheter in the left atrium. To the best of our knowledge no data are currently available about the hemodynamic consequences of a congenital atrial septal defect (ASD) after MitraClip repair. We report a case of MitraClip repair in a patient with ostium secundum ASD and ischemic cardiomyopathy, who needed intraprocedural closure of the defect for serious hemodynamic complications, secondary to worsening of the right ventricular function, increased pulmonary pressure and inversion of the interatrial shunt in right-to-left direction. These events, which were exacerbated by high blood levels of PaCO2 for the anesthesiological protocol used, led to left-side low-output syndrome and cardiorespiratory arrest. (c) 2015 Wiley Periodicals, Inc. PMID- 26354686 TI - WITHDRAWN: Development of EMC-based empirical model for estimating spatial distribution of pollutant loads and its application in rural areas of Korea. AB - The Publisher regrets that this article is an accidental duplication of an article that has already been published in Desalination Water Treat., 27:1-3, 175 188, http://dx.doi.org/10.5004/dwt.2011.2736. The duplicate article has therefore been withdrawn.The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy. PMID- 26354687 TI - Effects of surfactants on graphene oxide nanoparticles transport in saturated porous media. AB - Transport behaviors of graphene oxide nanoparticles (GONPs) in saturated porous media were examined as a function of the presence and concentration of anionic surfactant (SDBS) and non-ionic surfactant (Triton X-100) under different ionic strength (IS). The results showed that the GONPs were retained obviously in the sand columns at both IS of 50 and 200mmol/L, and they were more mobile at lower IS. The presence and concentration of surfactants could enhance the GONP transport, particularly as observed at higher IS. It was interesting to see that the GONP transport was surfactant type dependent, and SDBS was more effective to facilitate GONP transport than Triton X-100 in our experimental conditions. The advection-dispersion-retention numerical modeling followed this trend and depicted the difference quantitatively. Derjaguin-Landau-Verwey-Overbeek (DLVO) interaction calculations also were performed to interpret these effects, indicating that secondary minimum deposition was critical in this study. PMID- 26354689 TI - San copolymer membranes with ion exchangers for Cu(II) removal from synthetic wastewater by electrodialysis. AB - Heterogeneous membranes were obtained by using styrene-acrylonitrile copolymer (SAN) blends with low content of ion-exchanger particles (5wt.%). The membranes obtained by phase inversion were used for the removal of copper ions from synthetic wastewater solutions by electrodialytic separation. The electrodialysis was conducted in a three cell unit, without electrolyte recirculation. The process, under potentiostatic or galvanostatic control, was followed by pH and conductivity measurements in the solution. The electrodialytic performance, evaluated in terms of extraction removal degree (rd) of copper ions, was better under potentiostatic control then by the galvanostatic one and the highest (over 70%) was attained at 8V. The membrane efficiency at small ion-exchanger load was explained by the migration of resin particles toward the pores surface during the phase inversion. The prepared membranes were characterized by various techniques i.e. optical microscopy, Fourier transform infrared spectroscopy, scanning electron microscopy, thermogravimetric analysis and differential thermal analysis and contact angle measurements. PMID- 26354688 TI - Fenton-like degradation of Methylene Blue using paper mill sludge-derived magnetically separable heterogeneous catalyst: Characterization and mechanism. AB - For the paper industry, the disposal and management of the yielded sludge are a considerable challenge. In our work, the paper mill sludge-derived magnetically separable heterogeneous catalyst (PMS-Fe-380) was prepared easily through a facile synthesis method. The morphology and structure of PMS-Fe-380 were fully characterized by means of X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, and Brunauer-Emmet-Teller analysis. The catalytic activity of PMS-Fe-380 was evaluated by degradation of Methylene Blue (MB). The reusability and stability of PMS-Fe-380 were evaluated in five repeated runs, which suggested that PMS-Fe-380 manifested excellent stability of catalytic activity. Moreover, leaching tests indicated that the leached iron is negligible (<0.5mg/L). This study provides an alternative environmentally friendly reuse method for paper mill sludge and a novel catalyst PMS-Fe-380 that can be considered as a promising heterogeneous Fenton-like catalyst. PMID- 26354690 TI - Analysis of trace dicyandiamide in stream water using solid phase extraction and liquid chromatography UV spectrometry. AB - An improved method for trace level quantification of dicyandiamide in stream water has been developed. This method includes sample pretreatment using solid phase extraction. The extraction procedure (including loading, washing, and eluting) used a flow rate of 1.0mL/min, and dicyandiamide was eluted with 20mL of a methanol/acetonitrile mixture (V/V=2:3), followed by pre-concentration using nitrogen evaporation and analysis with high performance liquid chromatography ultraviolet spectroscopy (HPLC-UV). Sample extraction was carried out using a Waters Sep-Pak AC-2 Cartridge (with activated carbon). Separation was achieved on a ZIC((r))-Hydrophilic Interaction Liquid Chromatography (ZIC-HILIC) (50mm*2.1mm, 3.5MUm) chromatography column and quantification was accomplished based on UV absorbance. A reliable linear relationship was obtained for the calibration curve using standard solutions (R(2)>0.999). Recoveries for dicyandiamide ranged from 84.6% to 96.8%, and the relative standard deviations (RSDs, n=3) were below 6.1% with a detection limit of 5.0ng/mL for stream water samples. PMID- 26354691 TI - An experimental and thermodynamic equilibrium investigation of the Pb, Zn, Cr, Cu, Mn and Ni partitioning during sewage sludge incineration. AB - The effects of different chlorides and operational conditions on the distribution and speciation of six heavy metals (Pb, Zn, Cr, Cu, Mn and Ni) during sludge incineration were investigated using a simulated laboratory tubular-furnace reactor. A thermodynamic equilibrium investigation using the FactSage software was performed to compare the experimental results. The results indicate that the volatility of the target metals was enhanced as the chlorine concentration increased. Inorganic-Cl influenced the volatilization of heavy metals in the order of Pb>Zn>Cr>Cu>Mn>Ni. However, the effects of organic-Cl on the volatility of Mn, Pb and Cu were greater than the effects on Zn, Cr and Ni. With increasing combustion temperature, the presence of organic-Cl (PVC) and inorganic-Cl (NaCl) improved the transfer of Pb and Zn from bottom ash to fly ash or fuse gas. However, the presence of chloride had no obvious influence on Mn, Cu and Ni. Increased retention time could increase the volatilization rate of heavy metals; however, this effect was insignificant. During the incineration process, Pb readily formed PbSiO4 and remained in the bottom ash. Different Pb compounds, primarily the volatile PbCl2, were found in the gas phase after the addition of NaCl; the dominant Pb compounds in the gas phase after the addition of PVC were PbCl2, Pb(ClO4)2 and PbCl2O4. PMID- 26354692 TI - High NO2/NOx emissions downstream of the catalytic diesel particulate filter: An influencing factor study. AB - Diesel vehicles are responsible for most of the traffic-related nitrogen oxide (NOx) emissions, including nitric oxide (NO) and nitrogen dioxide (NO2). The use of after-treatment devices increases the risk of high NO2/NOx emissions from diesel engines. In order to investigate the factors influencing NO2/NOx emissions, an emission experiment was carried out on a high pressure common-rail, turbocharged diesel engine with a catalytic diesel particulate filter (CDPF). NO2 was measured by a non-dispersive ultraviolet analyzer with raw exhaust sampling. The experimental results show that the NO2/NOx ratios downstream of the CDPF range around 20%-83%, which are significantly higher than those upstream of the CDPF. The exhaust temperature is a decisive factor influencing the NO2/NOx emissions. The maximum NO2/NOx emission appears at the exhaust temperature of 350 degrees C. The space velocity, engine-out PM/NOx ratio (mass based) and CO conversion ratio are secondary factors. At a constant exhaust temperature, the NO2/NOx emissions decreased with increasing space velocity and engine-out PM/NOx ratio. When the CO conversion ratios range from 80% to 90%, the NO2/NOx emissions remain at a high level. PMID- 26354693 TI - Sunlight-driven reduction of silver ion to silver nanoparticle by organic matter mitigates the acute toxicity of silver to Daphnia magna. AB - Due to the unique antibacterial activities, silver nanoparticles (AgNPs) have been extensively used in commercial products. Anthropogenic activities have released considerable AgNPs as well as highly toxic silver ion (Ag(+)) into the aquatic environment. Our recent study revealed that ubiquitous natural organic matter (NOM) could reduce Ag(+) to AgNP under natural sunlight. However, the toxic effect of this process is not well understood. In this work, we prepared mixture solution of Ag(+) and AgNPs with varied Ag(+)% through the sunlight driven reduction of Ag(+) by NOM and investigated the acute toxicity of the solutions on Daphnia magna. Formation of AgNPs was demonstrated and characterized by comprehensive techniques and the fraction of unconverted Ag(+) was determined by ultrafiltration-inductively coupled plasma mass spectrometry determination. The formation of AgNPs enhanced significantly with the increasing of solution pH and cumulative photosynthetically active radiation of sunlight. The toxicity of the resulting solution was further investigated by using freshwater crustacean D. magna as a model and an 8hr-median lethal concentration (LC50) demonstrated that the reduction of Ag(+) by NOM to AgNPs significantly mitigated the acute toxicity of silver. These results highlight the importance of sunlight and NOM in the fate, transformation and toxicity of Ag(+) and AgNPs, and further indicate that the acute toxicity of AgNPs should be mainly ascribed to the dissolved Ag(+) from AgNPs. PMID- 26354694 TI - Remarkable promotion effect of trace sulfation on OMS-2 nanorod catalysts for the catalytic combustion of ethanol. AB - OMS-2 nanorod catalysts were synthesized by a hydrothermal redox reaction method using MnSO4 (OMS-2-SO4) and Mn(CH3COO)2 (OMS-2-AC) as precursors. SO4(2-)-doped OMS-2-AC catalysts with different SO4(2-) concentrations were prepared next by adding (NH4)2SO4 solution into OMS-2-AC samples to investigate the effect of the anion SO4(2-) on the OMS-2-AC catalyst. All catalysts were then tested for the catalytic oxidation of ethanol. The OMS-2-SO4 catalyst synthesized demonstrated much better activity than OMS-2-AC. The SO4(2-) doping greatly influenced the activity of the OMS-2-AC catalyst, with a dramatic promotion of activity for suitable concentration of SO4(2-) (SO4/catalyst=0.5% W/W). The samples were characterized by X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), inductively coupled plasma optical emission spectroscopy (ICP OES), NH3-TPD and H2-TPR techniques. The results showed that the presence of a suitable amount of SO4(2-) species in the OMS-2-AC catalyst could decrease the Mn O bond strength and also enhance the lattice oxygen and acid site concentrations, which then effectively promoted the catalytic activity of OMS-2-AC toward ethanol oxidation. Thus it was confirmed that the better catalytic performance of OMS-2 SO4 compared to OMS-2-AC is due to the presence of some residual SO4(2-) species in OMS-2-SO4 samples. PMID- 26354695 TI - Fabrication of ion doped WO3 photocatalysts through bulk and surface doping. AB - Na(+) doped WO3 nanowire photocatalysts were prepared by using post-treatment (surface doping) and in situ (bulk doping) doping methods. Photocatalytic degradation of Methyl Blue was tested under visible light irradiation, the results showed that 1wt.% Na(+) bulk-doped WO3 performed better, with higher photoactivity than surface-doped WO3. Photoelectrochemical characterization revealed the differences in the photocatalytic process for surface doping and bulk doping. Uniform bulk doping could generate more electron-hole pairs, while minimizing the chance of electron-hole recombination. Some bulk properties such as the bandgap, Fermi level and band position could also be adjusted by bulk doping, but not by surface doping. PMID- 26354696 TI - Catalytic activities of ultra-small beta-FeOOH nanorods in ozonation of 4 chlorophenol. AB - We report the catalytic properties of ultra-small beta-FeOOH nanorods in ozonation of 4-chlorophenol (4-CP). XRD, TEM, EDS, SAED, FTIR and BET were used to characterize the prepared material. Interaction between O3 and beta-FeOOH was evident from the FTIR spectra. The removal efficiency of 4-CP was significantly enhanced in the presence of beta-FeOOH compared to ozone alone. Removal efficiency of 99% and 67% was achieved after 40min in the presence of combined ozone and catalyst and ozone only, respectively. Increasing catalyst load increased COD removal efficiency. Maximum COD removal of 97% was achieved using a catalyst load of 0.1g/100mL of 4-CP solution. Initial 4-CP concentration was not found to be rate limiting below 2*10(-3)mol/L. The catalytic properties of the material during ozonation process were found to be pronounced at lower initial pH of 3.5. Two stage first order kinetics was applied to describe the kinetic behavior of the nanorods at low pH. The first stage of catalytic ozonation was attributed to the heterogeneous surface breakdown of O3 by beta-FeOOH, while the second stage was attributed to homogeneous catalysis initiated by reductive dissolution of beta-FeOOH at low pH. PMID- 26354697 TI - Environmental behaviors of phoxim with two formulations in bamboo forest under soil surface mulching. AB - Phoxim (emulsifiable concentrate (EC) and granules (G)) has been widely used in bamboo forests. The persistence and magnitude of phoxim residues in the crop and soil must be investigated to ensure human and environmental safety. The environmental behaviors of the two formulations were investigated in a bamboo forest under soil surface mulching conditions (CP) and non-covered cultivation conditions (NCP). The half-lives of phoxim in soil under the two conditions in soil were 4.1-6.2days (EC) and 31.5-49.5days (G), respectively. Phoxim in EC could be leached from the topsoil into the subsoil. A minimized leaching effect was observed for G under NCP. Inversely, an enhanced leaching effect was observed for G under CP. The G formulation resulted in more parent compound (in bamboo shoots) and metabolite (in soil) residues of phoxim than in the case of EC, especially under CP conditions. In addition, the intensity and duration of the formulation effect on soil pH adjustment from G were more obvious than that from EC. Results showed that the environmental behaviors (distribution, degradation, residue) of phoxim in the bamboo forest were significantly influenced by the type of formulation. The prolongation effect from phoxim G might cause persistence and long-term environmental risk. However, bamboo shoot consumption could be considered relatively safe after applying the recommended dose of the two phoxim formulations. PMID- 26354698 TI - Distribution of chlorpyrifos in rice paddy environment and its potential dietary risk. AB - Chlorpyrifos is one of the most extensively used insecticides in China. The distribution and residues of chlorpyrifos in a paddy environment were characterized under field and laboratory conditions. The half-lives of chlorpyrifos in the two conditions were 0.9-3.8days (field) and 2.8-10.3days (laboratory), respectively. The initial distribution of chlorpyrifos followed the increasing order of waterCu-SAPO-34 (HDP)>Cu-SAPO-34 (IM)>Cu-SAPO-34 (DP). Based on the obtained results, it was concluded that the NO conversion on Cu-SAPO-34 nanocatalysts was mainly related to the high reducibility of the isolated Cu(2+) ions and CuO species, the number of the acid sites and the dispersion of CuO species on SAPO-34. PMID- 26354703 TI - Influence of microbial community structure of seed sludge on the properties of aerobic nitrifying granules. AB - In order to evaluate the influence of microbial community structure of seed sludge on the properties of aerobic nitrifying granules, these granules were cultivated with different seed sludge, and the variation of microbial community and dominant bacterial groups that impact the nitrogen removal efficiency of the aerobic nitrifying granules were analyzed and identified using 16s rDNA sequence and denaturing gradient gel electrophoresis (DGGE) profiles. The results presented here demonstrated that the influence of the community structure of seed sludge on the properties of aerobic nitrifying granules was remarkable, and the granules cultivated by activated sludge from a beer wastewater treatment plant showed better performance, with a stable sludge volume index (SVI) value of 20mL/g, high extracellular polymeric substance (EPS) content of 183.3mg/L, high NH4(+)-N removal rate of 89.42% and abundant microbial population with 10 dominant bacterial groups. This indicated that activated sludge with abundant communities is suitable for use as seed sludge in culturing aerobic nitrifying granules. PMID- 26354704 TI - Biodegradation of nicosulfuron by a novel Alcaligenes faecalis strain ZWS11. AB - A bacterial strain ZWS11 was isolated from sulfonylurea herbicide-contaminated farmland soil and identified as a potential nicosulfuron-degrading bacterium. Based on morphological and physicochemical characterization of the bacterium and phylogenetic analysis of the 16S rRNA sequence, strain ZWS11 was identified as Alcaligenes faecalis. The effects of the initial concentration of nicosulfuron, inoculation volume, and medium pH on degradation of nicosulfuron were investigated. Strain ZWS11 could degrade 80.56% of the initial nicosulfuron supplemented at 500.0mg/L under the conditions of pH7.0, 180r/min and 30 degrees C after incubation for 6days. Strain ZWS11 was also capable of degrading rimsulfuron, tribenuron-methyl and thifensulfuron-methyl. Four metabolites from biodegradation of nicosulfuron were identified, which were 2-aminosulfonyl-N, N dimethylnicotinamide (M1), 4, 6-dihydroxypyrimidine (M2), 2-amino-4, 6 dimethoxypyrimidine (M3) and 2-(1-(4,6-dimethoxy-pyrimidin-2-yl)-ureido)-N,N dimethyl-nicotinamide (M4). Among the metabolites detected, M2 was reported for the first time. Possible biodegradation pathways of nicosulfuron by strain ZWS11 were proposed. The degradation proceeded mainly via cleavage of the sulfonylurea bridge, O-dealkylation, and contraction of the sulfonylurea bridge by elimination of a sulfur dioxide group. The results provide valuable information for degradation of nicosulfuron in contaminated environments. PMID- 26354705 TI - CO2 adsorption using TiO2 composite polymeric membranes: A kinetic study. AB - CO2 is the main greenhouse gas which causes global climatic changes on larger scale. Many techniques have been utilised to capture CO2. Membrane gas separation is a fast growing CO2 capture technique, particularly gas separation by composite membranes. The separation of CO2 by a membrane is not just a process to physically sieve out of CO2 through the controlled membrane pore size. It mainly depends upon diffusion and solubility of gases, particularly for composite dense membranes. The blended components in composite membranes have a high capability to adsorb CO2. The adsorption kinetics of the gases may directly affect diffusion and solubility. In this study, we have investigated the adsorption behaviour of CO2 in pure and composite membranes to explore the complete understanding of diffusion and solubility of CO2 through membranes. Pure cellulose acetate (CA) and cellulose acetate-titania nanoparticle (CA-TiO2) composite membranes were fabricated and characterised using SEM and FTIR analysis. The results indicated that the blended CA-TiO2 membrane adsorbed more quantity of CO2 gas as compared to pure CA membrane. The high CO2 adsorption capacity may enhance the diffusion and solubility of CO2 in the CA-TiO2 composite membrane, which results in a better CO2 separation. The experimental data was modelled by Pseudo first-order, pseudo second order and intra particle diffusion models. According to correlation factor R(2), the Pseudo second order model was fitted well with experimental data. The intra particle diffusion model revealed that adsorption in dense membranes was not solely consisting of intra particle diffusion. PMID- 26354706 TI - Photocatalytic properties of hierarchical BiOXs obtained via an ethanol-assisted solvothermal process. AB - In this study, bismuth oxyhalide (BiOXs (XCl, Br, I)) semiconductors were prepared by a simple solvothermal method, with ethanol serving as solvent and a series of tetrabutylammonium halide surfactants as halogen sources. Under identical synthetic conditions, BiOBr was more readily constructed into regular flower-like hierarchical architectures. The photocatalytic properties of the materials were studied by monitoring the degradation of rhodamine B (RhB), with visible light absorption, and colorless salicylic acid (SA). It was found that both RhB and SA were rapidly degraded on the surface of BiOBr. BiOCl was rather active for the degradation of RhB, but ineffective toward the degradation of SA. However, neither RhB nor SA could be degraded effectively in the case of BiOI. Further experiments such as UV-visible spectroscopy and detection of OH and O2(-) radicals suggest that the electronic structure of the BiOX photocatalysts is responsible for the difference in their activities. PMID- 26354707 TI - The first metagenome of activated sludge from full-scale anaerobic/anoxic/oxic (A2O) nitrogen and phosphorus removal reactor using Illumina sequencing. AB - The anaerobic/anoxic/oxic (A2O) process is globally one of the widely used biological sewage treatment processes. This is the first report of a metagenomic analysis using Illumina sequencing of full-scale A2O sludge from a municipal sewage treatment plant. With more than 530,000 clean reads from different taxa and metabolic categories, the metagenome results allow us to gain insight into the functioning of the biological community of the A2O sludge. There are 51 phyla and nearly 900 genera identified from the A2O activated sludge ecosystem. Proteobacteria, Bacteroidetes, Nitrospirae and Chloroflexi are predominant phyla in the activated sludge, suggesting that these organisms play key roles in the biodegradation processes in the A2O sewage treatment system. Nitrospira, Thauera, Dechloromonas and Ignavibacterium, which have abilities to metabolize nitrogen and aromatic compounds, are most prevalent genera. The percent of nitrogen and phosphorus metabolism in the A2O sludge is 2.72% and 1.48%, respectively. In the current A2O sludge, the proportion of Candidatus Accumulibacter is 1.37%, which is several times more than that reported in a recent study of A2O sludge. Among the four processes of nitrogen metabolism, denitrification related genes had the highest number of sequences (76.74%), followed by ammonification (15.77%), nitrogen fixation (3.88%) and nitrification (3.61%). In phylum Planctomycetes, four genera (Planctomyces, Pirellula, Gemmata and Singulisphaera) are included in the top 30 abundant genera, suggesting the key role of ANAMMOX in nitrogen metabolism in the A2O sludge. PMID- 26354708 TI - Adverse outcome pathway: Framework, application, and challenges in chemical risk assessment. PMID- 26354709 TI - Synthesis, characterization and application of ZnO-Ag as a nanophotocatalyst for organic compounds degradation, mechanism and economic study. AB - The current work deals with ZnO-Ag nanocomposites (in the wide range of x in the Zn1-xO-Agx chemical composition) synthesized using microwave assisted solution combustion method. The structural, morphological and optical properties of the samples were characterized by XRD (X-ray diffraction), FTIR (Fourier transform infrared spectrometry), SEM (scanning electron microscopy technique), EDX (energy dispersive X-ray spectrum), ICP (inductively coupled plasma technique), TEM (transmission electron microscopy), BET (Brunauer-Emmett-Teller method), UV-Vis (ultraviolet-visible spectrophotometer) and photoluminescence spectrophotometer. The photocatalytic activity of the ZnO-Ag was investigated by photo-degradation of Acid Blue 113 (AB 113) under UV illumination in a semi-batch reactor. This experiment showed that ZnO-Ag has much more excellent photocatalytic properties than ZnO synthesized by the same method. The enhanced photocatalytic activity was due to the decrease in recombination of photogenerated electron-holes. The results showed the improvement of ZnO photocatalytic activity and there is an optimum amount of Ag (3.5mol%) that needs to be doped with ZnO. The effect of operating parameters such as pH, catalyst dose and dye concentration were investigated. The reaction byproducts were identified by LC/MS (liquid chromatography/mass spectrometry) analysis and a pathway was proposed as well. Kinetic studies indicated that the decolorization process follows the first order kinetics. Also, the degradation percentage of AB 113 was determined using a total organic carbon (TOC) analyzer. Additionally, cost analysis of the process, the mechanism and the role of Ag were discussed. PMID- 26354710 TI - Temperature and food concentration have limited influence on the mixture toxicity of copper and Microcystis aeruginosa to Daphnia magna. AB - Standard ecotoxicity tests are conducted under constant and favorable experimental conditions. In natural communities, however, the toxicity of chemicals may be influenced by abiotic and biotic environmental factors. Firstly, the authors examined the influence of temperature and total food concentration on the nature of the combined effects of copper (Cu) and the cyanobacterium Microcystis aeruginosa to Daphnia magna (i.e., whether the combined effects deviated from noninteraction). Secondly, the authors investigated the relative influence of the percentage of M. aeruginosa in the diet, temperature, and total food concentration on chronic Cu toxicity to D. magna. The nature of the combined effects between Cu and M. aeruginosa (i.e., synergism according to the independent action reference model and noninteraction according to concentration addition reference model) was not affected by temperature and total food concentration. In line with other studies, the concentration addition reference model gave rise to more protective predictions of mixture toxicity than the independent action reference model, thus confirming the former model's suitability as a conservative scenario for evaluating mixture toxicity of Cu and M. aeruginosa under the temperature and food concentrations tested. Further, the 21-d median effective concentration for Cu based on reproduction varied between 20 MUg/L and 100 MUg/L, and the results indicate that the percentage of M. aeruginosa explained 76% of the variance in the Cu median effective concentration for reproduction, whereas the effects of temperature and total food were limited (together explaining 11% of the variance). The present study suggests that environmental risk assessment of Cu should consider specific situations where harmful M. aeruginosa blooms can co-occur with elevated Cu exposure. PMID- 26354711 TI - Greater parallel heterogeneity of airway narrowing and airway closure in asthma measured by high-resolution CT. AB - BACKGROUND: Heterogeneous airway narrowing and closure are characteristics of asthma. However, they have never been quantified by direct measurements of parallel sister airways obtained from image data, and the anatomical basis of these processes remains unknown. METHODS: Seven normal and nine asthmatic subjects underwent high-resolution CT, before and after methacholine challenge. Mean lumen areas of the entire airways were measured in 28 and 24 parallel sister airway pairs (a pair of airways arising from the same bifurcation) respectively (range 1.0-8.7 mm diameter). Heterogeneous narrowing was defined as the median difference in percentage narrowing between parallel sister airways. Forced oscillatory respiratory resistance (Rrs) and spirometry were measured before and after methacholine challenge conducted while supine. RESULTS: The airways of asthmatics were smaller at baseline, and following bronchoconstriction there were similar decreases in FEV1, increases in Rrs and mean narrowing of airways for asthmatic and non-asthmatic groups. Non-asthmatics required higher doses of methacholine than asthmatics to achieve the same changes. However, parallel heterogeneity (median (IQR) 33% (27-53%) vs 11% (9-18%), p<0.001) and airway closure (24.1% and 7.7%, p=0.001, chi(2)) were greater in asthmatics versus non asthmatics. CONCLUSION: We found clear evidence of differences in airway behaviour in the asthmatic group. Asthmatic airways were narrower at baseline and responded to inhaled methacholine by more heterogeneous narrowing of parallel sister airways and greater airway closure. PMID- 26354712 TI - Mini-Review of Published Reports on Coccidioidomycosis in China. AB - Coccidioidomycosis is a deep mycotic infection endemic to Americas. Although it has also been reported to occur in non-endemic areas, it has rarely been reported in China. We reviewed the literature on case reports of coccidioidomycosis in China from 1958 to 2015. A total of 30 cases were reported from 11 provinces in China, and 23 (76.7%) cases were men, and 23 (76.7%) were in 30-60 years old. Twenty-seven (90.0%) cases were reported from southern China. Twenty-four (80.0%) cases had no history of exposure in endemic areas. Three cases were immunosuppressed, four cases had chronic disease, and 23 cases (76.7 %) were otherwise healthy. Twenty cases (66.6%) had related lung infection, six had skin infection, three cases were in lymph node, and one in the cornea, one in the bone and joint, and three had systemic disseminated infection. All of the 30 cases were diagnosis upon finding spherules in histological examination. Interestingly, 12 (40.0%) patients underwent surgery and removed the focus of infection because they were misdiagnosed or suspected of tumor or cancer previously. Fifteen cases (50.0%) were treated with amphotericin B, fluconazole, clotrimazole or ketoconazole. Diagnosis of coccidioidomycosis is complex, and misdiagnosis can occur easily in non-epidemic areas such as China. PMID- 26354713 TI - Occurrence of chiral organochlorine compounds in the environmental matrices from King George Island and Ardley Island, west Antarctica. AB - Chiral organochlorine compounds (OCs) were measured in various environmental matrices (air, soil and vegetation) from west Antarctica using high resolution gas chromatography coupled with high resolution mass spectrometry (HRGC/HRMS). They were generally detected at a global background level compared with the previous studies. alpha-HCH and PCB-183 was observed in all the matrices except PCB-183 in two soil samples, while PCB-95, -136, -149, -174, -176 and o,p'-DDT were detected in most air but only a few solid matrices. Enantiomeric fractions (EFs) indicated that nonracemic residues of chiral OCs occurred in all the matrices and a wide variation of the EF values was observed in the vegetation. There was significant discrepancy between the EF values of PCB-183 and the racemic values, indicating that stereoselective depletion of PCB-183 was probably associated with the water-air exchange. The EFs values of alpha-HCH were generally lower than the racemic values but no statistical difference was obtained in all the matrices except lichen, supporting the assumption that water air exchange may make influence on long-range transport of alpha-HCH. PMID- 26354714 TI - Effect of Ankaferd Blood Stopper on Skin Superoxide Dismutase and Catalase Activities in Warfarin-Treated Rats. AB - AIM: Ankaferd Blood Stopper (ABS) is a new promising local hemostatic agent, and its mechanism on hemostasis has been shown by many studies. However, the effects of ABS on skin superoxide dismutase (SOD) and catalase (CAT) activities have not been investigated before. The aim of this study was to evaluate the effects of this new generation local hemostatic agent on warfarin-treated rats focusing on its the antioxidant potential in short-term soft tissue healing. METHODS: Twelve systemically warfarin treated (warfarin group) and 12 none treated Wistar Albino rats (control group) were selected for the trial. Rats in the warfarin group were treated intraperitonally with 0.1 mg/kg warfarin, and rats in the control group were given 1 mL/kg saline 3 days earlier to surgical procedure and continued until killing. All rats had incisions on dorsal dermal tissue, which was applied ABS or no hemostatic agent before suturing. Six of each group were killed on day 4, and the other 6 were killed on day 8. Blood and skin samples were taken. Prothrombin time (PT) in blood samples, CAT, and SOD activities in skin samples were determined. RESULTS: Warfarin treatment dose was found to be convenient and warfarin treatment increased the PT levels as expected. Warfarin treatment decreased CAT activity significantly compared to the control group. The ABS treatment significantly increased SOD activities in the warfarin group at the end of the eighth day. CONCLUSION: Ankaferd Blood Stopper acted positively in short term tissue healing by increasing SOD activity in warfarin-treated rats. Therefore, ABS may be suggeted as a promoting factor in tissue healing. PMID- 26354715 TI - Hyperthermia: an effective strategy to induce apoptosis in cancer cells. AB - Heat has been used as a medicinal and healing modality throughout human history. The combination of hyperthermia (HT) with radiation and anticancer agents has been used clinically and has shown positive results to a certain extent. However, the clinical results of HT treatment alone have been only partially satisfactory. Cell death following HT treatment is a function of both temperature and treatment duration. HT induces cancer cell death through apoptosis; the degree of apoptosis and the apoptotic pathway vary in different cancer cell types. HT-induced reactive oxygen species production are responsible for apoptosis in various cell types. However, the underlying mechanism of signal transduction and the genes related to this process still need to be elucidated. In this review, we summarize the molecular mechanism of apoptosis induced by HT, enhancement of heat-induced apoptosis, and the genetic network involved in HT-induced apoptosis. PMID- 26354716 TI - Diagnostic significance of PAX8 in thyroid squamous cell carcinoma. AB - Most types of thyroid carcinomas express PAX8 transcription factor; however, whether thyroid squamous cell carcinoma (SCC) also expresses PAX8, currently remains unknown. We herein examined the immunoreactivity of PAX8 in SCC of thyroidal and extrathyroidal origin, and discussed the diagnostic significance of PAX8. We immunohistochemically examined specimens from 11 SCC, 22 papillary thyroid carcinoma (PTC), 8 anaplastic thyroid carcinoma (ATC), and 2 mucoepidermoid carcinoma (MEC) cases as well as 5 uterine cervical SCC, 5 esophageal SCC, and 5 pulmonary SCC cases. The rates of PAX8-positive SCC, PTC, ATC, and MEC were 90.9%, 90.9%, 75.0%, and 100%, respectively. Two PAX8-negative PTC cases were cribriform variants. No uterine cervical, esophageal, or pulmonary SCC specimen reacted with PAX8 antibody. Thyroid transcription factor-1 (TTF-1) was positive in 9.1% and 95.5% of SCC and PTC cases, respectively, but negative in all ATC and MEC cases. These results demonstrate that PAX8 staining is useful for distinguishing between primary thyroid SCC and invasion or metastasis from extrathyroidal SCC. We recommend using an immunohistochemical panel of antibodies to PAX8 and TTF-1 to confirm a diagnosis of primary thyroid carcinoma. PMID- 26354717 TI - Expression of anti-Mullerian hormone and its type II receptor in germ cells of maturing rat testis. AB - This work aimed to clarify the expression and roles of anti-Mullerian hormone (AMH) and its type 2 receptor (AMHR2) in seminiferous tubules of maturing rat testes. By quantitative RT-PCR, we determined the relative expressions of Amh, Amhr2, Scp1, Rsbn1, Ngfr, and Rhox5 in rat testes aged 5-49 days (d), and in germ cells and Sertoli cells isolated from 21d testes. Smad 1,5 and 8 expressions were also determined in 21d testes and isolated germ cells. Moreover, we performed in situ hybridization (ISH) of Amh and Amhr2 in 21d testes, and immunohistochemical staining (IHCS) in 10, 15 and 21d testes using antibodies of AMH and AMHR2. In 21d testes, expression of the spermatocyte specific gene, Scp1, increased but that of the round spermatid specific gene, Rsbn1, was faint. By ISH and IHCS, expressions of AMH and AMHR2 were strongly observed in spermatocytes of 21d testes, but not in spermatogonia. In 21d testes, expressions of immature Sertoli cell specific gene, Ngfr, and mature Sertoli cell specific gene, Rhox5, were observed. IHCS confirmed the presence of AMH and AMHR2 in Sertoli cells. Smad 1, 5 and 8 were highly expressed in 21d testes and isolated germ cells. These results indicate that not only immature Sertoli cells but also spermatocytes express AMH and AMHR2 in maturing testes. In this study, we first clarified that spermatocytes coexpressed AMH and AMHR2 in rats. We speculated that AMH produced by spermatocytes and Sertoli cells binds AMHR2 of spermatocytes and acts through SMADs. PMID- 26354718 TI - Chemotherapy reduces PARP1 in cancers of the ovary: implications for future clinical trials involving PARP inhibitors. AB - BACKGROUND: PARP inhibitors have shown promising clinical results in cancer patients carrying BRCA1/2 mutations. Their clinical efficacy could logically be influenced by PARP1 protein levels in patient tumors. METHODS: We screened three cohorts of patients with ovarian cancer, totaling 313 samples, and evaluated PARP1 protein expression by immunohistochemistry with further validation by western blotting. RESULTS: We observed that up to 60 % of tumors showed little PARP1 protein expression. In serous ovarian tumors, comparing intratumoral PARP1 expression between chemo-naive and post-chemotherapy patients revealed a decrease in intratumoral PARP1 following chemotherapy in all three cohorts (immunohistochemistry: p < 0.001, n = 239; western blot: p = 0.012, n = 74). The findings were further confirmed in a selection of matched samples from the same patients before and after chemotherapy. CONCLUSION: Our data suggest that patients should be screened for PARP1 expression prior to therapy with PARP inhibitors. Further, the observed reduction of intratumoral PARP1 post chemotherapy suggests that treating chemo-naive patients with PARP inhibitors prior to the administration of chemotherapy, or concurrently, might increase the responsiveness to PARP1 inhibition. Thus, a change in the timing of PARP inhibitor administration may be warranted for future clinical trials. PMID- 26354719 TI - Can a sustainability and health scenario provide a realistic challenge to student nurses and provoke changes in practice? An evaluation of a training intervention. AB - Climate change and limited natural resources will impact on the sustainable supply and disposal of materials used in health care. Healthcare students need opportunities to reflect on the ecological footprint of health services to mitigate against negative effects on service delivery. In order to raise awareness of these issues, there is a need for evidence-based teaching tools which are relevant and meaningful to nursing practice. An evidence-based sustainability skills teaching session was delivered to 293 nursing students from child and adult health disciplines. Following the sessions, evaluation sheets were distributed to the participants, of which 290 responded. The majority of nurses valued both the delivery and the content of the training and some were motivated to complete further study. The evaluation provided valuable information on how to deliver sustainability education and important insights into where more information and support was needed in order to change practice. Embedding sustainability teaching in skill sessions appears to be a realistic way of informing and motivating learners to consider current and best practice. Following training, further evaluation of practice-based behaviour is needed. PMID- 26354720 TI - Co-morbid tobacco use disorder and depression: A re-evaluation of smoking cessation therapy in depressed smokers. AB - BACKGROUND AND OBJECTIVES: To provide a critical evaluation of nicotine use disorder co-morbidity in persons with major depressive disorder (MDD) or its subsyndromal presentations. We focus on how a diagnosis of current or past MDD may shape access to smoking cessation therapy, and highlight the unique challenges that this group of smokers has to overcome to receive adequate treatment. METHODS: A literature search was performed using PubMed for studies published between January 1995 and March 2015 using the following keywords and combination of keywords (co-morbidity, co-occurrence, and dual-diagnosis) and (nicotine dependence, cigarette smoking, tobacco dependence, tobacco use disorder) and (depression, major depression, unipolar mood disorders) and (self medication). A total of 93 articles were identified. Of these, 31 studies were included in the analysis. RESULTS: We found that: a) depressed smokers are motivated to quit; b) smoking cessation does not exacerbate symptoms of depression; c) depression does not have a negative impact on smoking cessation outcomes, and d) the self-medication hypothesis does not account for tobacco dependence and depression co-morbidity. DISCUSSION AND CONCLUSIONS: Our review of the relevant evidence suggests the importance and clinical significance of undertaking smoking cessation treatment for depressed smokers. SCIENTIFIC SIGNIFICANCE: Our findings support the need for increased attention to developing and implementing smoking cessation treatments for depressed smokers. SCIENTIFIC SIGNIFICANCE: Our findings support the need for increased attention to developing and implementing smoking cessation treatments for depressed smokers. PMID- 26354721 TI - Placement of the Decompression Tube as a Bridge to Surgery for Acute Malignant Left-Sided Colonic Obstruction. AB - PURPOSE: The aim of this study is to investigate the feasibility, safety, and effectiveness of placing the decompression tube as a bridge to surgery for acute malignant left-sided colonic obstruction. METHODS: From January 2009 to August 2014, consecutive patients with acute malignant left-side colonic obstruction underwent placement of the decompression tube as a bridge to surgery in our center. The technical and clinical success of placing the decompression tube was evaluated. Clinical success was defined as relief of obstructive symptoms within 48 h after placing the decompression tube. Elective tumor resection was performed 7-9 days after colonic decompression. The types of surgery, primary anastomosis rate, and follow-up findings were analyzed. RESULTS: Twenty patients with acute malignant left-side colonic obstruction underwent placement of the decompression tube as a bridge to surgery. Placement of decompression tube was technically successful in all patients. No procedure-related complication occurred. Clinical success was achieved in 19 patients. Elective tumor resection and primary anastomosis were successfully performed in all 19 patients. The postoperative complications included wound infection (n = 2) and anastomotic stenosis (n = 1). CONCLUSION: Decompression tube can serve as an easy, safe, and effective bridge to subsequent surgery for patients with acute malignant left-sided colonic obstruction. PMID- 26354722 TI - DFS70 Autoantibodies are Rare in Healthy Danish Individuals but may Still Serve as a Diagnostic Aid. PMID- 26354723 TI - Diaphragm and genioglossus corticomotor excitability in patients with obstructive sleep apnea and control subjects. AB - Corticomotor excitability of peripheral muscles appears to be altered in patients with obstructive sleep apnea. However, there is no evidence of such alteration for upper airway/respiratory muscles that are involved in the pathophysiology of this disease. The aim of this study was to compare the effects of hypercapnic stimulation on diaphragm and genioglossus corticomotor excitability in awake healthy subjects versus patients with obstructive sleep apnea. Corticomotor excitability was assessed by transcranial magnetic stimulation in 12 untreated apneic men (48 +/- 10 years; body mass index = 28.9 +/- 4.7 kg m(-2); apnea hypopnoea index = 41 +/- 23 events per hour) and nine control men (45 +/- 10 years; body mass index = 27.3 +/- 3.3 kg m(-2); apnea-hypopnoea index = 7 +/- 4 events per hour). Assessments included diaphragm and genioglossus expiratory motor thresholds, and transcranial magnetic stimulation-induced motor-evoked potential characteristics obtained while breathing room air or 5% CO2 (random order) and then 7% CO2 both balanced with pure O2. Transcranial magnetic stimulation twitches were applied during early inspiration and end expiration. Diaphragm motor-evoked potential amplitudes increased and expiratory diaphragm motor-evoked potential latencies decreased during CO2-induced increase in ventilatory drive, with no difference in these responses between patients with obstructive sleep apnea and control subjects. Expiratory genioglossus motor evoked potential amplitudes were significantly lower in patients with obstructive sleep apnea than in control subjects. Baseline activity of the genioglossus increased with increasing FiCO2, this effect being significantly higher in patients with obstructive sleep apnea than in control subjects. However, neither genioglossus motor-evoked potential amplitudes nor latencies were significantly modified with increasing FiCO2 both in patients with obstructive sleep apnea and in control subjects. Corticomotor excitability of genioglossus and diaphragm are not altered during CO2-induced increase in ventilatory drive in patients with obstructive sleep apnea. PMID- 26354724 TI - An improved tensile deformation model for in-situ dendrite/metallic glass matrix composites. AB - With regard to previous tensile deformation models simulating the tensile behavior of in-situ dendrite-reinforced metallic glass matrix composites (MGMCs) [Qiao et al., Acta Mater. 59 (2011) 4126; Sci. Rep. 3 (2013) 2816], some parameters, such as yielding strength of the dendrites and glass matrix, and the strain-hardening exponent of the dendrites, are estimated based on literatures. Here, Ti48Zr18V12Cu5Be17 MGMCs are investigated in order to improve the tensile deformation model and reveal the tensile deformation mechanisms. The tensile behavior of dendrites is obtained experimentally combining nano-indentation measurements and finite-element-method analysis for the first time, and those of the glass matrix and composites are obtained by tension. Besides, the tensile behavior of the MGMCs is divided into four stages: (1) elastic-elastic, (2) elastic-plastic, (3) plastic-plastic (work-hardening), and (4) plastic-plastic (softening). The respective constitutive relationships at different deformation stages are quantified. The calculated results coincide well with the experimental results. Thus, the improved model can be applied to clarify and predict the tensile behavior of the MGMCs. PMID- 26354725 TI - Characterization of exogenous DNA mobility in live cells through fluctuation correlation spectroscopy. AB - The spatial-temporal dynamics of delivered DNA is a critical aspect influencing successful gene delivery. A comprehensive model of DNA lipoplex trafficking through live cells has yet to be demonstrated. Here the bioimaging approaches Raster Image Correlation Spectroscopy (RICS) and image-Means Square Displacement (iMSD) were applied to quantify DNA mechanical dynamics in live cells. DNA lipoplexes formed from DNA with a range of 21 bp to 5.5 kbp exhibited a similar range of motion within the cytoplasm of myoblast cells regardless of size. However, the rate of motion was dictated by the intracellular location, and DNA cluster size. This analysis demonstrated that the different transport mechanisms either had a size dependent mobility, including random diffusion, whereas other mechanisms were not influenced by the DNA size such as active transport. The transport mechanisms identified followed a spatial dependence comparable to viral trafficking of non-active transport mechanism upon cellular entry, active transport within the cytoplasm and further inactive transportation along the peri nuclear region. This study provides the first real-time insight into the trafficking of DNA delivered through lipofection using image-based fluctuation correlation spectroscopy approaches. Thereby, gaining information with single particle sensitivity to develop a deeper understanding of DNA lipoplex delivery through the cell. PMID- 26354727 TI - Hadza hunter-gatherer men do not have more masculine digit ratios (2D:4D). AB - OBJECTIVES: The ratio between the length of the second and the length of the fourth digit (2D:4D) is sexually dimorphic such that males of many species possess a lower ratio than females, particularly in the right hand. Still, men and women often exhibit overlapping 2D:4D ranges and the ratio is highly variable between populations. In order to further explore populational variability, we chose to analyze 2D:4D in the Hadza, a population of hunter-gatherers living in Tanzania. MATERIALS AND METHODS: Data were collected separately by two researchers over the course of three years (1998, 2001, 2006) from 152 adult participants (male: n = 76, female: n = 76). Independent samples t-tests were used to explore sex differences, paired samples t-tests were used to explore directional effects within each sex, and linear regression and one-way ANOVA were used to test possible age effects. RESULTS: In none of the years, or pooled (n = 152), did we find evidence that adult men have a lower 2D:4D than adult women. If anything, the data suggest that women in this population have a significantly lower right hand 2D:4D than men (P < 0.001, d = 0.57). In contrast, left hand 2D:4D did not exhibit a sex difference (P = 0.862, d = 0.03). DISCUSSION: These findings challenge the current view that lower 2D:4D in men is a uniform characteristic of our species. Cross-populational variance in 2D:4D may be related to known patterns of hormonal variation resulting from both genetic and environmental mechanisms, though this relationship merits further investigation. PMID- 26354728 TI - When efficacy beliefs affect team attributions: relationships between self- and collective efficacy beliefs and team attributions over time. AB - BACKGROUND: This study investigated the extent to which efficacy beliefs and perceptions of team performance influenced team causal attributions overtime. METHODS: A total of 258 undergraduate students were assigned to a three or four person team and played three games against three different opponents in a semi round robin team bowling tournament. RESULTS: Multilevel modelling analyses revealed that individuals' perceptions in team performance were positively associated with internal, stable, and team controllable attributions. Collective efficacy beliefs positively predicted team attributions overtime; whereas, self efficacy beliefs were a negative predictor of team attributions across the tournament. CONCLUSIONS: The results indicated that individuals' perceptions of their team's success/failure were the stronger determinant of team attributions than their team's winning/losing and, as well as, the efficacy beliefs - team attributions relationships were moderated by time. PMID- 26354726 TI - Cross-species models of human melanoma. AB - Although transformation of melanocytes to melanoma is rare, the rapid growth, systemic spread, as well as the chemoresistance of melanoma present significant challenges for patient care. Here we review animal models of melanoma, including murine, canine, equine, and zebrafish models, and detail the immense contribution these models have made to our knowledge of human melanoma development, and to melanocyte biology. We also highlight the opportunities for cross-species comparative genomic studies of melanoma to identify the key molecular events that drive this complex disease. PMID- 26354729 TI - An eight week school-based intervention with circuit training improves physical fitness and reduces body fat in male adolescents. AB - BACKGORUND: School-based intervention programs have been found to effectively improve various fitness and health parameters. However, only few studies so far examined the effect of circuit training in school environment during physical education (PE) classes. The aim of the current study was to examine the effects of an eight-week circuit training on physical fitness and body fat in male adolescents. METHODS: Thirty nine, 16-year old male high-school students participated in the current study. The students were randomly assigned to intervention and control groups. The intervention period lasted eight weeks and consisted of two circuit training sessions per week performed during regular PE classes. Total body fat was calculated by using bioelectrical impedance analysis. Physical fitness parameters such as cardiorespiratory fitness, flexibility, jumping ability and isometric arm strength were assessed through a battery of field tests. Finally, resting heart rate and blood pressure levels were assessed with an automatic monitor. RESULTS: By the end of the intervention period, total body fat and resting systolic blood pressure were significantly lower while cardiorespiratory fitness was significantly improved in the circuit training group only (P<0.05). In the control group Body Mass Index and total body fat percentage were significantly increased when compared pre- and post-intervention period (P<0.05). CONCLUSIONS: Eight weeks of circuit training during PE classes appeared to be effective in improving various physical fitness parameters and reducing fatness in male adolescents. PMID- 26354730 TI - Impact of Screening Implementing HCV Screening of Persons Born 1945-1965: A Primary Care Case Study. AB - BACKGROUND: In August 2012, the Centers for Disease Control and Prevention released recommendations to screen persons born from 1945 to 1965 for hepatitis C virus (HCV). In September 2012, Warm Springs Health and Wellness Center (WSHWC) initiated a quality improvement (QI) project to conduct HCV screening among all patients in this birth cohort. METHODS: Screening rates were tracked using a nationally standardized HCV screening measure in the Indian Health Service. At the end of the project period, WSHWC staff took a brief survey to review the impact of the HCV QI Project. RESULTS: Screening for HCV among eligible patients at WSHWC increased from 5% (47/938) in September 2012 to 76% (593/785) in September 2014. Survey data indicated that clinicians felt increased screening for HCV had a positive impact on patient communication and care. CONCLUSIONS: Primary care clinics can successfully increase HCV screening in a relatively short time period. Age based screening recommendation may provide opportunities to increase communication with others at risk for HCV. As more patients are screened, it will be important to ensure appropriate linkage to care for HCV patients. PMID- 26354731 TI - Regulated expression of virulence gene mviN provides protective immunity and colonization control of Salmonella in poultry. AB - Current live attenuated vaccines for control of Salmonella in poultry persist in the ceca and may persist in the environment. In this paper we report the construction and characterization of the vaccine efficacy of a Salmonella mutant strain with inducible mviN expression and rapid clearance from the host. The mutant was effective in oral immunization of the broiler chicken host against a virulent Salmonella oral challenge strain, having a mean 7*10(6)CFU/g in the ceca of unvaccinated controls compared to a mean 2*10(3)CFU/g in the ceca of vaccinated chickens at 4 weeks post-challenge (6 weeks of age). The mutant strain also demonstrated immunogenicity, reduced organ colonization, and rapid clearance in broiler chickens within 3 weeks of inoculation. PMID- 26354732 TI - Putting the "Metal" Back in Meta-Analysis. PMID- 26354733 TI - Early maternal relational traumatic experiences and psychopathological symptoms: a longitudinal study on mother-infant and father-infant interactions. AB - Early maternal relational traumas and psychopathological risk can have an impact on mother-infant interactions. Research has suggested the study of fathers and of their psychological profiles as protection or risk factors. The aim of the paper is to assess the quality of parental interactions during feeding in families with mothers with early traumatic experiences. One hundred thirty-six (N = 136) families were recruited in gynecological clinics: Group A included families with mothers who experienced early sexual/physical abuse; Group B was composed of families with mothers who experienced early emotional abuse or neglect; and Group C comprised healthy controls. The subjects participated in a 10-month longitudinal protocol [at the fourth month of pregnancy (T0), 3 months after child birth (T1), and 6 months after child birth (T2)] that included an observation of mother-infant and father-infant interactions during feeding (Scala di Valutazione dell'Interazione Alimentare [SVIA]) and a self-reporting 90-item Symptom Checklist-Revised (SCL-90-R). Maternal higher rates of depression and early traumatic experiences of neglect and emotional abuse predicted more maladaptive scores on the affective state of the dyad SVIA subscale. Paternal anxiety predicted more severe levels of food refusal in the child during feeding. PMID- 26354734 TI - Drug reaction with eosinophilia and systemic symptoms (DRESS): clinicopathological study of 45 cases. AB - BACKGROUND: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare and severe adverse drug reaction. Large detailed studies of histopathological features of DRESS are sparse and suggest an association between keratinocyte damage and the severity of visceral involvement. OBJECTIVES: To describe the dermatopathological features in a large series of DRESS and their possible association with clinical features and the severity of the disease. METHODS: A retrospective analysis of the clinicobiological and dermatopathological features in a monocentric cohort of patients with DRESS. RESULTS: From January 2005 to January 2013, 45 patients were validated as probable or definite cases of DRESS. The median age was 64 years (range 3-87). The most frequent clinical and biological features included: fever >=38.5 degrees C (95%), facial oedema (72%), enlarged lymph nodes (51%), visceral involvement (75%), blood eosinophilia (97%) and atypical lymphocytes (82%). Severe DRESS occurred in 24% and a fatal outcome in 6% of patients. Histopathological analysis showed that no specific histopathological pattern was characteristic for DRESS. However, several changes in different cutaneous compartments were observed in 2 of 3 of cases. Spongiosis (55%) and keratinocyte damage (53%) were the most common epidermal changes. Spongiosis was associated with non-severe DRESS (P = 0.041) whereas confluent keratinocyte necrosis correlated with severe DRESS (P = 0.011). Vascular changes were frequent (88%). A moderate dermal perivascular lymphocytic infiltrate was invariably present, containing eosinophils, neutrophils and/or atypical lymphocytes in 57% of cases. CONCLUSIONS: Epidermal changes are indicative for the severity of DRESS. PMID- 26354735 TI - Synergistic Inhibition of R5 HIV-1 by the Fusion Protein (FLSC) IgG1 Fc and Maraviroc in Primary Cells: Implications for Prevention and Treatment. AB - BACKGROUND: Antiretroviral (ARV) drugs targeting retroviral enzymes have been extensively employed to treat HIV-1 infection. Drawbacks of this approach include cost, toxicity, and the eventual emergence of resistant strains that threaten prophylactic and/or therapeutic efficacy. Accordingly, efforts to develop next generation ARV approaches are warranted, particularly if they can offer a higher threshold of resistance. We have previously shown that FLSC, a fusion protein containing gp120(BAL) and the D1 and D2 domains of human CD4, specifically binds CCR5, an important cellular co-receptor, and inhibits the entry of R5 HIV isolates. (FLSC) IgG1, a fusion of FLSC and the hinge-C(H)2-C(H)3 region of human IgG1, has an increased antiviral activity, likely due to the resultant bivalency. METHODS: In this study, we show CCR5 reduction upon (FLSC) IgG1 treatment both by standard flow cytometry and visualized using a novel nanoparticle method. A beta lactamase virus-cell fusion assay was used to quantify (FLSC) IgG1 inhibition of HIV-1 entry into both cell lines and primary cells. Synergistic anti-viral activities of (FLSC) IgG1 and MVC in primary cells were evaluated by measuring supernatant p24 levels via ELISA and calculated using the MacSynergyTM II program. RESULTS: We previously reported that treatment with the CCR5 small molecule antagonist Maraviroc (MVC) increased the apparent exposure of the (FLSC) IgG1 binding sites on CCR5, leading us to wonder if the two compounds used in combination might synergize in their anti-viral activity. Here we show that this is indeed the case. We demonstrate that fusion protein (FLSC) IgG1, strongly synergizes with the CCR5 antagonist Maraviroc to successfully inhibit both MVC sensitive and MVC-resistant R5 HIV-1. CONCLUSION: Observed synergy between (FLSC) IgG1 and MVC was high in both, cell lines and primary PBMCs. This has relevance for future in vivo studies. In addition, synergy occurred both with MVC-sensitive viruses and MVC-resistant viruses, partially restoring the inhibitory effect of MVC. These findings suggest that a combinatorial treatment based on these two compounds has potential merit and that future in vivo studies are warranted. PMID- 26354736 TI - Infant Tracheostomy. PMID- 26354737 TI - A novel method for producing unequal sized droplets in micro- and nanofluidic channels. AB - We propose a novel method for producing unequal sized droplets through breakup of droplets. This method does not have the disadvantages of the available methods and also reduces the dependence of the droplets volume ratio on the inlet velocity of the system by up to 26 percent. The employed method for investigating the proposed system relies on 3D numerical simulation using the VOF algorithm and the results have been obtained with various valve ratios for both the micro- and nanoscale. The results indicate that the droplet length during the breakup process increases linearly with time. The droplet length at the nanoscale is smaller than that at the micro scale. It has been shown that the maximum local capillary number in this system is 2.5 times the average capillary number. Therefore one can use the analytical theories based on the low capillary number assumptions to investigate the method. PMID- 26354738 TI - PRIS may be diagnosed before ICU period for patients undergoing cardiopulmonary bypass. AB - There are many published articles on the clinical manifestations of propofol related infusion syndrome (PRIS), but they are not the same in each case.(1)Moreover, PRIS is only encountered infrequently and, therefore, it may create a diagnostic challenge. Nearly all of the published articles on PRIS are related to the use of long-term (> 48 hour) propofol infusion with a dose range of at least 4-5 mg/kg/h. In this case, not only a short duration, but also a low dose propofol administration seems to induce PRIS. A 73-year-old male patient under cardiopulmonary bypass (CPB) suffered from some clinical symptoms of PRIS, such as hyperlactatemia and persistent low metabolic acidosis which promptly resolved on the discontinuation of propofol. Therefore, we suggest that any propofol administration (bolus or infusion) may result in such clinical symptoms, which may be the earliest indicators of PRIS. When those symptoms are observed on propofol administration during cardiopulmonary bypass (CPB), the perfusionist must alert both the anaesthesiologist and the surgeon to stop the propofol in order to prevent the patient from further adverse effects of PRIS. PMID- 26354739 TI - Clinical significance of no-reflow in different stages of primary angioplasty among patients with acute myocardial infarctions. AB - BACKGROUND: The coronary no-reflow (NR) phenomenon, which is associated with poor clinical outcomes, is usually referred to as a post-percutaneous coronary intervention (PCI) state. NR can occur in different stages of the PCI procedure, not only including the post-stenting stage, but from balloon pre-dilation to pre stenting. The clinical significance of NR in the different stages of the PCI procedure is unclear. The purpose of the current study was to analyze the clinical and angiographic characteristics, the prognosis for NR patients in the aforementioned two stages and to determine the predictors of NR in the early stage. METHODS: Between January 2009 and December 2013, a total of 420 consecutive patients with ST-segment elevation myocardial infarction (STEMI) underwent primary PCI. Sixty-three patients (15%) with NR constituted the study population. The patients were divided into an early NR group and a subsequent NR group. The clinical and angiographic findings were compared between the two groups. Multivariate logistic regression was used to determine the predictors for early NR. The long-term clinical outcomes after PCI were analyzed. RESULTS: Regarding the baseline characteristics, we identified that the early NR group had statistically significant effects on the higher percentage of diabetes mellitus (42.9% vs. 20%), lower admission systolic blood pressure (SBP) (102.2 +/- 8.3 mmHg vs. 110.5 +/- 7.6 mmHg), higher percentage of Killip classification III (71.4% vs. 45.7%,) and longer reperfusion time (7.1 +/- 2.3 h vs. 5.88 +/- 2.2 h) compared to the subsequent NR group.There were significant differences between the two groups with respect to the percentage of initial thrombolysis in myocardial infarction (TIMI) flow 0/1 (64.3% vs. 37.1%), target lesion length (31.4 +/- 13.6 mm vs. 20.5 +/- 17.3 mm) and thrombus score ? 4 (67.9% vs. 42.9%; p < 0.05 for all). Multiple stepwise logistic regression analysis indicated that an admission SBP < 100 mmHg (OR = 4.580; 95% CI = 1.385-15.150; p = 0.0130), reperfusion time ? 6 h (OR = 4.978; 95% CI = 1.468-16.882; p = 0.010) and a thrombus score ? 4 (OR = 2.708; 95% CI = 0.833-8.799; p = 0.008) were the independent determinants of the early NR. During a 1-year follow-up, the all cause mortality and overall major adverse cardiac events (MACEs) in the early NR group occurred significantly more often than in the subsequent NR group (28.6% vs. 5.7% and 35.7% vs. 14.3%, respectively, p ITALIC! <0.05). The early NR group had a lower left ventricular ejection fraction (LVEF) (42.5 +/- 4.7 vs. 47.8 +/- 3.5, p ITALIC! < 0.001) and a larger left ventricular end diastolic diameter (LVEDD) (56.0 +/- 4.0 vs. 51.5 +/- 4.7, p = 0.001) at the end of the follow-up. CONCLUSION: Early NR patients during primary PCI have more severe baseline clinical and angiographic characteristics, as well as a poorer long-term prognosis. PMID- 26354740 TI - Activated clotting time test alone is inadequate to optimize therapeutic heparin dosage adjustment during post-cardiopulmonary resuscitational extracorporeal membrane oxygenation (e-CPR). AB - BACKGROUND: We conducted an observational study to evaluate the relationship between activated clotting time (ACT) and activated partial thromboplastin time (aPTT) tests, anticipating the possibility that the ACT will become a substitute test for the aPTT in post-CPR extracorporeal membrane oxygenation (e-CPR). PATIENTS AND METHODS: Three hundred and fifteen paired ACT and aPTT samples were derived from 60 in-hospital e-CPR patients and were divided into three groups according to the observed ACT value: low level (ACT < 170 s, Group A), intended target level (ACT 170-210 s Group B) and high level (ACT > 210 s, Group C). The relationship of aPTT in each group was analyzed. RESULTS: The mean ACT and aPTT values were 189.39 +/- 48.27 s (IQR, 163-202) and 71.85 +/- 45.32 s (IQR, 44.5 81.8), respectively. Although the observed mean ACT value of 189.39 s was similar to the intended mean target value of 190 s (p = 0.823), the observed mean aPTT value (71.85 s) was significantly lower than the predicted mean target value (77.5 s, p = 0.027). Despite the mean ACT values being significantly different in each group (p < 0.0001), the mean aPTT values were not statistically different between Groups A and B (p = 0.317). Of the Group B samples (n = 139), only 31 samples (22.3%) met the optimal therapeutic aPTT range. Pearson's correlation coefficient for Group B showed only a weak correlation between ACT and aPTT (r = 0.177; p = 0.037). CONCLUSIONS: Our study demonstrates that the ACT test alone does not seem to be enough to optimize therapeutic heparin dosage adjustment during e-CPR. PMID- 26354741 TI - Pulmonary collapse alone provides effective de-airing in cardiac surgery: a prospective randomized study. AB - OBJECTIVES: We previously described and showed that the method for cardiac de airing involving: (1) bilateral, induced pulmonary collapse by opening both pleurae and disconnecting the ventilator before cardioplegic arrest and (2) gradual pulmonary perfusion and ventilation after cardioplegic arrest is superior to conventional de-airing methods, including carbon dioxide insufflation of the open mediastinum. This study investigated whether one or both components of this method are responsible for the effective de-airing of the heart. METHODS: Twenty patients scheduled for open, left heart surgery were randomized to two de-airing techniques: (1) open pleurae, collapsed lungs and conventional pulmonary perfusion and ventilation; and (2) intact pleurae, expanded lungs and gradual pulmonary perfusion and ventilation. RESULTS: The number of cerebral microemboli measured by transcranial Doppler sonography was lower in patients with open pleurae 9 (6-36) vs 65 (36-210), p = 0.004. Residual intra-cardiac air grade I or higher as monitored by transesophageal echocardiography 4-6 minutes after weaning from cardiopulmonary bypass was seen in few patients with open pleurae 0 (0%) vs 7 (70%), p = 0.002. CONCLUSIONS: Bilateral, induced pulmonary collapse alone is the key factor for quick and effective de-airing of the heart. Gradual pulmonary perfusion and ventilation, on the other hand, appears to be less important. PMID- 26354742 TI - Is preoperative anaemia really a predictor of adverse outcomes after cardiac surgery? PMID- 26354743 TI - Commentary on: Reliability of the Thoratec HeartMate II flow measurements and alarms in the presence of reduced or non-existent flow. PMID- 26354744 TI - Commentary on: Clinical evaluation of contemporary oxygenators. PMID- 26354745 TI - Alternatives for arterial inflow in open surgical descending and thoracoabdominal aortic repair. AB - Surgical repair of the descending and thoracoabdominal aorta is regularly performed with the support of extracorporeal circulation. Femoral artery cannulation is the standard for arterial inflow, but presents, along with extremity hypoperfusion, the risk of embolization and malperfusion with retrograde aortic perfusion. There are alternatives for arterial inflow to avoid the drawbacks of the standard approach while accommodating different perfusion strategies. Ideally, with a broadened perfusion armamentarium, the choice of arterial inflow could be individualized to provide safe and efficient extracorporeal circulation. PMID- 26354746 TI - Versatile minimized system--a step towards safe perfusion. AB - A growing body of evidence indicates the superiority of minimized cardiopulmonary bypass (CPB) systems compared to conventional systems in terms of inflammatory reactions and transfusion requirements. Evident benefits of minimized CPB systems, however, do not come without consequences. Kinetic-assisted drainage, as used in these circuits, can result in severe fluctuations of venous line pressures and, consequently, fluctuation of the blood flow delivered to the patient. Furthermore, subatmospheric venous line pressures can cause gaseous microemboli. Another limitation is the absence of cardiotomy suction, which can lead to excessive blood loss via a cell saver. The most serious limitation of minimized circuits is that these circuits are very constrained in the case of complications or changing of the surgery plan. We developed a versatile minimized system (VMS) with a priming volume of about 600 ml. A compliance chamber in the venous line decreases peaks of pressure fluctuations. This chamber also acts as a bubble trap. Additionally, the open venous reservoir is connected parallel to the venous line and excluded from the circulation during an uncomplicated CPB. This reservoir can be included in the circulation via a roller pump and be used as a cardiotomy reservoir. The amount and rate of returned blood in the circulation is regulated by a movable level detector. Further, the circuit can easily be converted to an open system with vacuum-assisted venous drainage in the case of unexpected complications. The VMS combines the benefits of minimized circuits with the versatility and safety of a conventional CPB system. Perfusionists familiar with this system can secure an adequate and timely response at expected and unexpected intraoperative complications. PMID- 26354747 TI - An insight into the potentially old-wonder molecule-quercetin: the perspectives in foresee. AB - Use of phyto-medicine and digitalization of phyto-compounds has been fallen enthralling field of science in recent years. Quercetin, a flavonoid with brilliant citron yellow pigment, is typically found in fruits and leafy vegetables in reasonable amount. Quercetin's potentials as an antioxidant, immune modulator, antiinflammatory, anti-cancer, and others have been the subject of interest in this review. Although, profiling the insights in to the molecular characterization of quercetin with various targets provided the loop-holes in understanding the knowledge for the aforementioned mechanisms, still necessitates research globally to unearth it completely. Thus, the available science on the synthesis and significant role played by the old molecule - quercetin which does wonders even now have been vividly explained in the present review to benefit the scientific community. PMID- 26354748 TI - Mechanisms of ammonia and ammonium transport by rhesus-associated glycoproteins. AB - In this study we characterized ammonia and ammonium (NH3/NH4(+)) transport by the rhesus-associated (Rh) glycoproteins RhAG, Rhbg, and Rhcg expressed in Xenopus oocytes. We used ion-selective microelectrodes and two-electrode voltage clamp to measure changes in intracellular pH, surface pH, and whole cell currents induced by NH3/NH4(+) and methyl amine/ammonium (MA/MA(+)). These measurements allowed us to define signal-specific signatures to distinguish NH3 from NH4(+) transport and to determine how transport of NH3 and NH4(+) differs among RhAG, Rhbg, and Rhcg. Our data indicate that expression of Rh glycoproteins in oocytes generally enhanced NH3/NH4(+) transport and that cellular changes induced by transport of MA/MA(+) by Rh proteins were different from those induced by transport of NH3/NH4(+). Our results support the following conclusions: 1) RhAG and Rhbg transport both the ionic NH4(+) and neutral NH3 species; 2) transport of NH4(+) is electrogenic; 3) like Rhbg, RhAG transport of NH4(+) masks NH3 transport; and 4) Rhcg is likely to be a predominantly NH3 transporter, with no evidence of enhanced NH4(+) transport by this transporter. The dual role of Rh proteins as NH3 and NH4(+) transporters is a unique property and may be critical in understanding how transepithelial secretion of NH3/NH4(+) occurs in the renal collecting duct. PMID- 26354750 TI - A novel mechanism of myostatin regulation by its alternative splicing variant during myogenesis in avian species. AB - Myostatin (MSTN) is a key negative regulator of muscle growth and development, and an increase of muscle mass is achieved by inhibiting MSTN signaling. In the current study, five alternative splicing isoforms of MSTN mRNAs in avian species were identified in various tissues. Among these five, three truncated forms of myostatin, MSTN-B, -C, and -E created premature stop codons and produced partial MSTN prodomains encoded from exon 1. MSTN-B is the second dominant isoform following full-length MSTN-A, and their expression was dynamically regulated during muscle development of chicken, turkey, and quail in vivo and in vitro. To clarify the function of MSTN-B, two stable cell lines of quail myoblasts (QM7) were generated to overexpress MSTN-A or MSTN-B. Interestingly, MSTN-B promoted both cell proliferation and differentiation similar to the function of the MSTN prodomain to counteract the negative role of MSTN on myogenesis. The coimmunoprecipitation assay revealed that MSTN-B binds to MSTN-A and reduces the generation of mature MSTN. Furthermore, the current study demonstrated that the partial prodomain encoded from exon 1 is critical for binding of MSTN-B to MSTN A. Altogether, these data imply that alternative splicing isoforms of MSTN could negatively regulate pro-myostatin processing in muscle cells and prevent MSTN mediated inhibition of myogenesis in avian species. PMID- 26354749 TI - MicroRNA signature of inflamed lymphatic endothelium and role of miR-9 in lymphangiogenesis and inflammation. AB - The lymphatics have emerged as critical players in the progression and resolution of inflammation. The goal of this study was to identify specific microRNAs (miRNAs) that regulate lymphatic inflammatory processes. Rat mesenteric lymphatic endothelial cells (LECs) were exposed to the proinflammatory cytokine tumor necrosis factor-alpha for 2, 24, and 96 h, and miRNA profiling was carried out by real-time PCR arrays. Our data demonstrate a specific set of miRNAs that are differentially expressed (>1.8-fold and/or P < 0.05) in LECs in response to tumor necrosis factor-alpha and are involved in inflammation, angiogenesis, endothelial mesenchymal transition, and cell proliferation and senescence. We further characterized the expression of miRNA 9 (miR-9) that was induced in LECs and in inflamed rat mesenteric lymphatics. Our results showed that miR-9 overexpression significantly repressed NF-kappaB expression and, thereby, suppressed inflammation but promoted LEC tube formation, as well as expression of the prolymphangiogenic molecules endothelial nitric oxide synthase and VEGF receptor type 3. LEC viability and proliferation and endothelial-mesenchymal transition were also significantly induced by miR-9. This study provides the first evidence of a distinct profile of miRNAs associated with LECs during inflammation. It also identifies the critical dual role of miR-9 in fine-tuning the balance between lymphatic inflammatory and lymphangiogenic pathways. PMID- 26354751 TI - Hypoxia-inducible factors in T lymphocyte differentiation and function. A Review in the Theme: Cellular Responses to Hypoxia. AB - Low oxygen concentrations or hypoxia is a trait common to inflamed tissues. Therefore it is not surprising that pathways of hypoxic stress response, largely governed by hypoxia-inducible factors (HIF), are highly relevant to the proper function of immune cells. HIF expression and stabilization in immune cells can be triggered not only by hypoxia, but also by a variety of stimuli and pathological stresses associated with leukocyte activation and inflammation. In addition to its role as a sensor of oxygen scarcity, HIF is also a major regulator of immune cell metabolic function. Rapid progress is being made in elucidating the roles played by HIF in diverse aspects of both innate and adaptive immunity. Here we discuss a number of breakthroughs that have shed light on how HIF expression and activity impact the differentiation and function of diverse T cell populations. The insights gained from these findings may serve as the foundation for future therapies aimed at fine-tuning the immune response. PMID- 26354752 TI - Patients' views and experiences of technology based self-management tools for the treatment of hypertension in the community: A qualitative study. AB - BACKGROUND: Patients with hypertension in the community frequently fail to meet treatment goals. The optimal way to organize and deliver care to hypertensive patients has not been clearly identified. The powerful on-board computing capacity of mobile devices, along with the unique relationship individuals have with newer technologies, suggests that they have the potential to influence behaviour. However, little is known regarding the views and experiences of patients using such technology to self-manage their hypertension and associated lifestyle behaviours. The aim of this study was to explore patients' views and experiences of using technology based self-management tools for the treatment of hypertension in the community. METHODS: This focus group study was conducted with known hypertensive patients over 45 years of age who were recruited in a community setting in Ireland. Taped and transcribed semi-structured interviews with a purposeful sample involving 50 participants in six focus groups were used. Framework analysis was utilized to analyse the data. RESULTS: Four key inter related themes emerged from the analysis: individualisation; trust; motivation; and communication. The globalisation of newer technologies has triggered many substantial and widespread behaviour changes within society, yet users are unique in their use and interactions with such technologies. Trust is an ever present issue in terms of its potential impact on engagement with healthcare providers and motivation around self-management. The potential ability of technology to influence motivation through carefully selected and tailored messaging and to facilitate a personalised flow of communication between patient and healthcare provider was highlighted. CONCLUSIONS: Newer technologies such as mobile devices and the internet have been embraced across the globe despite technological challenges and concerns regarding privacy and security. In the design and development of technology based self-management tools for the treatment of hypertension, flexibility and security are vital to allow and encourage patients to customise, personalise and engage with their devices. PMID- 26354753 TI - Erratum to: Association between pain, neuropsychiatric symptoms, and physical function in dementia: a systematic review and meta-analysis. PMID- 26354754 TI - Exploring attitudes and preferences for dementia screening in Britain: contributions from carers and the general public. AB - BACKGROUND: Dementia is becoming one of the most important emerging public health concerns in a generation. In societal approaches to the mitigation of major disease 'burden', population screening can sometimes provide an effective approach to improving detection of disease and outcomes. However the acceptability of a systematic population screening programme for dementia, to the British public, is not known. METHODS: A Patient and Public Involvement (PPI) event was organised to give members of the public from the East of England an opportunity to offer their perspectives and to comment on the findings of a systematic literature review looking at attitudes and preferences towards screening for dementia. The event was attended by 36 members of the public and eight national Alzheimer's Society Research Network volunteers. The morning discussion contained a presentation, which defined population screening for attendees but contained no reference to the findings of the review. In the afternoon, findings of the review were presented and a discussion on the results was facilitated. The discussions were recorded, transcribed and subjected to thematic analysis. The NVivo qualitative data software was used to facilitate this process. RESULTS: A total of 23 key themes emerged in relation to the carer and general population. The most frequent themes which emerged were the low levels of understanding and awareness around the dementia syndrome; the acceptability and validity of any tests; costs to the National Health Service (NHS); an individual's existing health status existing health status; financial/profit motive for screening; the inability to change prognosis; and the importance and availability of support. CONCLUSIONS: Factors such as personal beliefs, experiences and attitudes to health impact on decisions to be screened for dementia. A number of additional concerns were raised which were not previously identified in the systematic literature review. These were around the economic incentives for screening (profit motive), the provision of social support, and the economic/social impacts of screening programmes. This may reflect cultural differences in health and social care funding models between Britain and other countries where previous research was conducted. PMID- 26354755 TI - An Examination of the Nature of Erotic Talk. AB - Using a mixed-methods study, we provided the first systematic documentation and exploration of erotic talk. In Study 1 (N = 95), participants provided 569 erotic talk statements in an anonymous online survey, which we classified, using a modified thematic analysis, as being representative of eight themes. In Study 2 (N = 238), we quantified individual differences in these themes, subjected them to factor analysis, and examined the nomological network surrounding them with measures of relationship and sexual satisfaction, sociosexuality, and personality. The eight initial categories represented two higher order factors, which we call individualist talk and mutualistic talk. These factors were orthogonal in factor analysis and distinct in their nomological network. While the majority of people reported using erotic talk, we found few sex differences in its use. PMID- 26354757 TI - Complement deposition in autoimmune hemolytic anemia is a footprint for difficult to-detect IgM autoantibodies. AB - In autoimmune hemolytic anemia autoantibodies against erythrocytes lead to increased clearance of the erythrocytes, which in turn results in a potentially fatal hemolytic anemia. Depending on whether IgG or IgM antibodies are involved, response to therapy is different. Proper identification of the isotype of the anti-erythrocyte autoantibodies is, therefore, crucial. However, detection of IgM autoantibodies can be challenging. We, therefore, set out to improve the detection of anti-erythrocyte IgM. Direct detection using a flow cytometry-based approach did not yield satisfactory improvements. Next, we analyzed whether the presence of complement C3 on a patient's erythrocytes could be used for indirect detection of anti-erythrocyte IgM. To this end, we fractionated patients' sera by size exclusion chromatography and tested which fractions yielded complement deposition on erythrocytes. Strikingly, we found that all patients with C3 on their erythrocytes according to standard diagnostic tests had an IgM anti erythrocyte component that could activate complement, even if no such autoantibody had been detected with any other test. This also included all tested patients with only IgG and C3 on their erythrocytes, who would previously have been classified as having an IgG-only mediated autoimmune hemolytic anemia. Depleting patients' sera of either IgG or IgM and testing the remaining complement activation confirmed this result. In conclusion, complement activation in autoimmune hemolytic anemia is mostly IgM-mediated and the presence of covalent C3 on patients' erythrocytes can be taken as a footprint of the presence of anti-erythrocyte IgM. Based on this finding, we propose a diagnostic workflow that will aid in choosing the optimal treatment strategy. PMID- 26354756 TI - Identification of novel microRNA signatures linked to acquired aplastic anemia. AB - Emerging evidence indicates that microRNA control and modulate immunity. MicroRNA have not been investigated in acquired aplastic anemia, a T-cell-mediated immune disease. Analysis of 84 microRNA expression levels in CD4(+) and CD8(+) T cells of patients with aplastic anemia revealed concurrent down-regulation of miR-126 3p, miR-145-5p, miR-223-3p, and miR-199a-5p (>3-fold change, P<0.05) in both T cell populations, which were unique in aplastic anemia compared to other hematologic disorders. MiR-126-3p and miR-223-3p were down-regulated in CD4(+) T effector memory cells, and miR-126-3p, miR-145-5p, and miR-223-3p were down regulated in CD8(+) T effector memory and terminal effector cells. Successful immunosuppressive therapy was associated with restoration to normal expression levels of miR-126-3p, miR-145-5p, and miR-223-3p (>2-fold change, P<0.05). In CD4(+) and CD8(+) T cells in aplastic anemia patients, MYC and PIK3R2 were up regulated and proved to be targets of miR-145-5p and miR-126-3p, respectively. MiR-126-3p and miR-145-5p knockdown promoted proliferation and increased interferon-gamma and granzyme B production in both CD4(+) and CD8(+) T cells. Our work describes previously unknown regulatory roles of microRNA in T-cell activation in aplastic anemia, which may open a new perspective for development of effective therapy. Clinicaltrials.gov identifier: NCT 01623167. PMID- 26354758 TI - Hyaluronic acid concentration in liver diseases. AB - The aim of this study was to evaluate the effect of liver diseases of different etiologies and clinical severity of liver cirrhosis on the serum level of hyaluronic acid. The results were compared with noninvasive markers of liver fibrosis: APRI, GAPRI, HAPRI, FIB-4 and Forn's index. Serum samples were obtained from 20 healthy volunteers and patients suffering from alcoholic cirrhosis (AC) 57 patients, non-alcoholic cirrhosis (NAC)-30 and toxic hepatitis (HT)-22. Cirrhotic patients were classified according to Child-Pugh score. Hyaluronic acid concentration was measured by the immunochemical method. Non-patented indicators were calculated using special formulas. The mean serum hyaluronic acid concentration was significantly higher in AC, NAC and HT group in comparison with the control group. There were significant differences in the serum hyaluronic acid levels between liver diseases, and in AC they were significantly higher than those in NAC and HT group. The serum hyaluronic acid level differs significantly due to the severity of cirrhosis and was the highest in Child-Pugh class C. The sensitivity, specificity, accuracy, positive and negative predictive values and the area under the ROC curve for hyaluronic acid and all non-patented algorithms were high and similar to each other. We conclude that the concentration of hyaluronic acid changes in liver diseases and is affected by the severity of liver cirrhosis. Serum hyaluronic acid should be considered as a good marker for noninvasive diagnosis of liver damage, but the combination of markers is more useful. PMID- 26354759 TI - Flower color polymorphism maintained by overdominant selection in Sisyrinchium sp. AB - Negative frequency-dependent selection derived from positive frequency-dependent foraging is the best-known selection force maintaining genetic polymorphism within a population. However, in flowering plants, positive frequency-dependent foraging by pollinators is expected to accelerate the loss of low-frequency morphs by conferring a fitness advantage to the common morph, leading to monomorphism. In Japan, a non-native species, Sisyrinchium sp., exhibits conspicuous flower color polymorphism within a population comprising both purple morphs (homozygous recessive) and white morphs (heterozygous or homozygous dominant). Here we quantified genotype-specific reproductive success in order to reveal the contribution of overdominant selection on the maintenance of flower color polymorphism in this species. In artificial pollination experiments using individuals with identified genotypes, female reproductive success was higher in the heterozygote than in either homozygote. The frequency of purple morphs in natural populations (ca. 31%) is similar to the frequency predicted by overdominant selection (25%). Our results suggest that overdominant selection contributes to the maintenance of color morphs in the natural population of this species. PMID- 26354761 TI - Evidence in duck for supporting alteration of incubation temperature may have influence on methylation of genomic DNA. AB - Incubation temperature has an immediate and long-term influence on the embryonic development in birds. DNA methylation as an important environment-induced mechanism could serve as a potential link between embryos' phenotypic variability and temperature variation, which reprogrammed by DNA (cytosine-5) methyltransferases (DNMTS) and Methyl-CpG binding domain proteins (MBPS) 3&5 (MBD3&5). Five genes in DNMTS and MBPS gene families were selected as target genes, given their important role in epigenetic modification. In this study, we aimed to test whether raising incubation temperature from 37.8 degrees C to 38.8 degrees C between embryonic days (ED) 1-10, ED10-20 and ED20-27 have effect on DNA methylation and whether DNMTS, MBPS play roles in thermal epigenetic regulation of early development in duck. Real-time quantitative PCR analysis showed that increased incubation temperature by 1 degrees C has remarkably dynamic effect on gene expression levels of DNMTS and MBPS. Slight changes in incubation temperature significantly increased mRNA levels of target genes in breast muscle tissue during ED1-10, especially for DNMT1, DNMT3A and MBD5. In addition, higher temperature significantly increased enzyme activities of DNMT1 in leg muscle during ED10-20, liver tissue during ED1-10, ED20-27 and DNMT3A in leg muscle and breast muscle tissue during ED10-20. These results suggest that incubation temperature has an extended effect on gene expression levels and enzyme activities of DNMTS and MBPS, which provides evidence that incubation temperature may influence DNA methylation in duck during early developmental stages. Our data indicated that DNMTS and MBPS may involved in thermal epigenetice regulation of embryos during the early development in duck. The potential links between embryonic temperature and epigenetic modification need further investigation. PMID- 26354762 TI - Litter use by laying hens in a commercial aviary: dust bathing and piling. AB - The laying hen industry, including in the United States, is responding to social concerns about hen welfare by implementing alternative housing systems such as the aviary, to provide more space and resources to large groups of hens. Data detailing the behavior of hens in commercial aviaries is needed to determine hens' use of the resources in order to understand their impact on hen welfare. The open litter area of aviaries provides additional space for hens during the day. Litter is also a substrate for dust bathing which is a strongly motivated natural behavior. Hens are often synchronous in their performance of dust bathing, which may lead to overcrowding in the litter area. Additionally, the open litter area can facilitate expression of unusual behavior such as flock piling (defined as the occurrence of densely grouped clusters of hens, resulting from no obvious cause and occurring randomly throughout the day and flock cycle) which may be a welfare concern. Therefore, we conducted observations of hen occupancy of the open litter area and the performance of dust bathing and flock piling across 3 production points (peak lay, mid lay and end of lay) for two flocks of Lohmann White laying hens housed in a commercial aviary. All areas of the open litter area were occupied to the same degree. Hens performed dust bathing throughout the day but showed peak dust bathing activity in the afternoon for Flock 1 (all P < 0.001) and in the late morning for Flock 2 (all P < 0.001). Overall, 174 incidents of piling behavior were observed between the 2 flocks, with piles varying in size, duration, and time of occurrence; however, no smothering was detected. Crowding on the open litter area sometimes occurred during peak periods of synchronous dust bathing and when hens piled. Further research is needed to understand the welfare implications of individual hen use of the open litter area and the causes and welfare implications of hen piling. PMID- 26354760 TI - Structure, function, and evolution of plant NIMA-related kinases: implication for phosphorylation-dependent microtubule regulation. AB - Microtubules are highly dynamic structures that control the spatiotemporal pattern of cell growth and division. Microtubule dynamics are regulated by reversible protein phosphorylation involving both protein kinases and phosphatases. Never in mitosis A (NIMA)-related kinases (NEKs) are a family of serine/threonine kinases that regulate microtubule-related mitotic events in fungi and animal cells (e.g. centrosome separation and spindle formation). Although plants contain multiple members of the NEK family, their functions remain elusive. Recent studies revealed that NEK6 of Arabidopsis thaliana regulates cell expansion and morphogenesis through beta-tubulin phosphorylation and microtubule destabilization. In addition, plant NEK members participate in organ development and stress responses. The present phylogenetic analysis indicates that plant NEK genes are diverged from a single NEK6-like gene, which may share a common ancestor with other kinases involved in the control of microtubule organization. On the contrary, another mitotic kinase, polo-like kinase, might have been lost during the evolution of land plants. We propose that plant NEK members have acquired novel functions to regulate cell growth, microtubule organization, and stress responses. PMID- 26354763 TI - Disordered breathing during sleep and exercise in idiopathic pulmonary fibrosis. PMID- 26354765 TI - Evaluation of the efficacy and safety of dual antiplatelet therapy with or without warfarin in patients with a clinical indication for DAPT and chronic anticoagulation: A meta-analysis of observational studies. AB - OBJECTIVE: To compare the efficacy and safety of dual antiplatelet therapy (DAPT) and triple therapy (TT, dual antiplatelet plus warfarin) in patients with myocardial infarction (MI) or PCI with stenting (PCI-S) who also require chronic oral anticoagulation. BACKGROUND: Recommendations for the optimal antiplatelet/anticoagulant treatment regimen for patients undergoing PCI-S or MI who also require oral anticoagulation are largely based on evidence from observational studies and expert opinions. METHODS: A systematic search was performed for studies comparing TT vs. DAPT in patients post PCI-S or MI and requiring chronic anticoagulation. Primary outcome was all-cause mortality. Secondary outcomes were ischemic stroke, major bleeding, MI, and stent thrombosis. Pooled relative risks (RR) were calculated using random effects model. RESULTS: A total of 17 studies were included, with 14,921 patients [TT: 5,819(39%) and DAPT: 9,102(61%)] and a mean follow-up of 1.6 years. The majority of patients required oral anticoagulation for atrial fibrillation. Compared to DAPT, patients treated with TT had no significant difference in all-cause mortality [RR: 0.81, 95% confidence interval (CI): 0.61-1.08, P = 0.15], MI [RR 0.74, 95% CI: 0.51-1.06, P = 0.10], and stent thrombosis [RR 0.67, 95% CI: 0.35 1.30, P = 0.24]. Patients treated with TT had significantly increased risk of major bleeding [RR 1.20, 95% CI: 1.03-1.39, P = 0.02], whereas the risk for ischemic stroke was significantly lower [RR 0.59, 95% CI: 0.38-0.92, P = 0.02]. CONCLUSIONS: All-cause mortality appears similar in patients treated with TT or DAPT although TT was associated with higher rates of major bleeding and a lower risk for ischemic stroke. (c) 2015 Wiley Periodicals, Inc. PMID- 26354766 TI - Dabigatran use in elderly patients with atrial fibrillation. AB - In elderly patients (>= 75 years), evidence of dabigatran efficacy is lacking and increased vigilance is warranted. We aimed to assess dabigatran effectiveness and safety in elderly patients in real-world practice. We conducted a population based study using administrative databases, in Quebec (1999-2013). Dabigatran users (110/150 mg) were compared with matched warfarin users with regard to stroke and bleeding events. Age was categorised into < 75 or >= 75 years. Propensity score adjusted models were used. The cohort consisted of 15,918 dabigatran users and 47,192 matched warfarin users, with 67.3% being elderly patients. The elderly predominantly used the lower dose (80.1%) while younger patients mainly used the higher dose (80.0%). In multivariable analyses adjusted for propensity score, the risk of stroke in elderly patients using dabigatran, was no different than the risk in warfarin users (HR 1.05, 95% CI: 0.93, 1.19) regardless of dabigatran dose. However, dabigatran was associated with lower rates of intracranial haemorrhage (HR 0.60, 95% CI: 0.47-0.76) and higher rates of gastrointestinal bleeding (HR 1.30 95% CI: 1.14-1.50) when compared to warfarin. Based on real-life experience, dabigatran can offer an alternative to warfarin in elderly patients, with fewer intracranial bleeding events. However, caution is warranted for gastrointestinal bleeding. PMID- 26354764 TI - Joint Associations of Diet, Lifestyle, and Genes with Age-Related Macular Degeneration. AB - PURPOSE: Unhealthy lifestyles have been associated with increased odds for age related macular degeneration (AMD). Whether this association is modified by genetic risk for AMD is unknown and was investigated. DESIGN: Interactions between healthy lifestyles AMD risk genotypes were studied in relation to the prevalence of AMD, assessed 6 years later. PARTICIPANTS: Women 50 to 79 years of age in the Carotenoids in Age-Related Eye Disease Study with exposure and AMD data (n=1663). METHODS: Healthy lifestyle scores (0-6 points) were assigned based on Healthy Eating Index scores, physical activity (metabolic equivalent of task hours/week), and smoking pack years assessed in 1994 and 1998. Genetic risk was based on Y402H in complement factor H (CFH) and A69S in age-related maculopathy susceptibility locus 2 (ARMS2). Additive and multiplicative interactions in odds ratios were assessed using the synergy index and a multiplicative interaction term, respectively. MAIN OUTCOME MEASURES: AMD presence and severity were assessed from grading of stereoscopic fundus photographs taken in 2001-2004. AMD was present in 337 women, 91% of whom had early AMD. RESULTS: The odds of AMD were 3.3 times greater (95% confidence interval [CI], 1.8-6.1) in women with both low healthy lifestyle score (0-2) and high-risk CFH genotype (CC), relative to those who had low genetic risk (TT) and high healthy lifestyle scores (4-6). There were no significant additive (synergy index [SI], 1.08; 95% CI, 0.70-1.67) or multiplicative (Pinteraction=0.94) interactions in the full sample. However, when limiting the sample to women with stable diets before AMD assessment (n=728) the odds for AMD associated with low healthy lifestyle scores and high-risk CFH genotype were strengthened (odds ratio, 4.6; 95% CI, 1.8-11.6) and the synergy index was significant (SI, 1.34; 95% CI, 1.05-1.70). Adjusting for dietary lutein and zeaxanthin attenuated, and therefore partially explained, the joint association. There were no significant additive or multiplicative interactions for ARMS2 and lifestyle score. CONCLUSIONS: Having unhealthy lifestyles and 2 CFH risk alleles increased AMD risk (primarily in the early stages), in an or additive or greater (synergistic) manner. However, unhealthy lifestyles increased AMD risk regardless of AMD risk genotype. PMID- 26354767 TI - Dependence of Human Colorectal Cells Lacking the FBW7 Tumor Suppressor on the Spindle Assembly Checkpoint. AB - FBW7 (F-box and WD repeat domain containing 7), also known as FBXW7 or hCDC4, is a tumor suppressor gene mutated in a broad spectrum of cancer cell types. As a component of the SCF E3 ubiquitin ligase, FBW7 is responsible for specifically recognizing phosphorylated substrates, many important for tumor progression, and targeting them for ubiquitin-mediated degradation. Although the role of FBW7 as a tumor suppressor is well established, less well studied is how FBW7-mutated cancer cells might be targeted for selective killing. To explore this further, we undertook a genome-wide RNAi screen using WT and FBW7 knockout colorectal cell lines and identified the spindle assembly checkpoint (SAC) protein BUBR1, as a candidate synthetic lethal target. We show here that asynchronous FBW7 knockout cells have increased levels of mitotic APC/C substrates and are sensitive to knockdown of not just BUBR1 but BUB1 and MPS1, other known SAC components, suggesting a dependence of these cells on the mitotic checkpoint. Consistent with this dependence, knockdown of BUBR1 in cells lacking FBW7 results in significant cell aneuploidy and increases in p53 levels. The FBW7 substrate cyclin E was necessary for the genetic interaction with BUBR1. In contrast, the establishment of this dependence on the SAC requires the deregulation of multiple substrates of FBW7. Our work suggests that FBW7 knockout cells are vulnerable in their dependence on the mitotic checkpoint and that this may be a good potential target to exploit in FBW7-mutated cancer cells. PMID- 26354768 TI - Suppression of Meiotic Recombination by CENP-B Homologs in Schizosaccharomyces pombe. AB - Meiotic homologous recombination (HR) is not uniform across eukaryotic genomes, creating regions of HR hot- and coldspots. Previous study reveals that the Spo11 homolog Rec12 responsible for initiation of meiotic double-strand breaks in the fission yeast Schizosaccharomyces pombe is not targeted to Tf2 retrotransposons. However, whether Tf2s are HR coldspots is not known. Here, we show that the rates of HR across Tf2s are similar to a genome average but substantially increase in mutants deficient for the CENP-B homologs. Abp1, which is the most prominent of the CENP-B family members and acts as the primary determinant of HR suppression at Tf2s, is required to prevent gene conversion and maintain proper recombination exchange of homologous alleles flanking Tf2s. In addition, Abp1-mediated suppression of HR at Tf2s requires all three of its domains with distinct functions in transcriptional repression and higher-order genome organization. We demonstrate that HR suppression of Tf2s can be robustly maintained despite disruption to chromatin factors essential for transcriptional repression and nuclear organization of Tf2s. Intriguingly, we uncover a surprising cooperation between the histone methyltransferase Set1 responsible for histone H3 lysine 4 methylation and the nonhomologous end joining pathway in ensuring the suppression of HR at Tf2s. Our study identifies a molecular pathway involving functional cooperation between a transcription factor with epigenetic regulators and a DNA repair pathway to regulate meiotic recombination at interspersed repeats. PMID- 26354769 TI - Complementation of Yeast Genes with Human Genes as an Experimental Platform for Functional Testing of Human Genetic Variants. AB - While the pace of discovery of human genetic variants in tumors, patients, and diverse populations has rapidly accelerated, deciphering their functional consequence has become rate-limiting. Using cross-species complementation, model organisms like the budding yeast, Saccharomyces cerevisiae, can be utilized to fill this gap and serve as a platform for testing human genetic variants. To this end, we performed two parallel screens, a one-to-one complementation screen for essential yeast genes implicated in chromosome instability and a pool-to-pool screen that queried all possible essential yeast genes for rescue of lethality by all possible human homologs. Our work identified 65 human cDNAs that can replace the null allele of essential yeast genes, including the nonorthologous pair yRFT1/hSEC61A1. We chose four human cDNAs (hLIG1, hSSRP1, hPPP1CA, and hPPP1CC) for which their yeast gene counterparts function in chromosome stability and assayed in yeast 35 tumor-specific missense mutations for growth defects and sensitivity to DNA-damaging agents. This resulted in a set of human-yeast gene complementation pairs that allow human genetic variants to be readily characterized in yeast, and a prioritized list of somatic mutations that could contribute to chromosome instability in human tumors. These data establish the utility of this cross-species experimental approach. PMID- 26354770 TI - Differential effects of ribosomal proteins and Mg2+ ions on a conformational switch during 30S ribosome 5'-domain assembly. AB - Ribosomal protein S4 nucleates assembly of the 30S ribosome 5' and central domains, which is crucial for the survival of cells. Protein S4 changes the structure of its 16S rRNA binding site, passing through a non-native intermediate complex before forming native S4-rRNA contacts. Ensemble FRET was used to measure the thermodynamic stability of non-native and native S4 complexes in the presence of Mg(2+) ions and other 5'-domain proteins. Equilibrium titrations of Cy3 labeled 5'-domain RNA with Cy5-labeled protein S4 showed that Mg(2+) ions preferentially stabilize the native S4-rRNA complex. In contrast, ribosomal proteins S20 and S16 act by destabilizing the non-native S4-rRNA complex. The full cooperative switch to the native complex requires S4, S16, and S20 and is achieved to a lesser degree by S4 and S16. The resulting thermodynamic model for assembly of the 30S body illustrates how ribosomal proteins selectively bias the equilibrium between alternative rRNA conformations, increasing the cooperativity of rRNA folding beyond what can be achieved by Mg(2+) ions alone. PMID- 26354771 TI - Controlling mRNA stability and translation with the CRISPR endoribonuclease Csy4. AB - The bacterial CRISPR endoribonuclease Csy4 has recently been described as a potential RNA processing tool. Csy4 recognizes substrate RNA through a specific 28-nt hairpin sequence and cleaves at the 3' end of the stem. To further explore applicability in mammalian cells, we introduced this hairpin at various locations in mRNAs derived from reporter transgenes and systematically evaluated the effects of Csy4-mediated processing on transgene expression. Placing the hairpin in the 5' UTR or immediately after the start codon resulted in efficient degradation of target mRNA by Csy4 and knockdown of transgene expression by 20- to 40-fold. When the hairpin was incorporated in the 3' UTR prior to the poly(A) signal, the mRNA was cleaved, but only a modest decrease in transgene expression (~2.5-fold) was observed. In the absence of a poly(A) tail, Csy4 rescued the target mRNA substrate from degradation, resulting in protein expression, which suggests that the cleaved mRNA was successfully translated. In contrast, neither catalytically inactive (H29A) nor binding-deficient (R115A/R119A) Csy4 mutants were able to exert any of the effects described above. Generation of a similar 3' end by RNase P-mediated cleavage was unable to rescue transgene expression independent of Csy4. These results support the idea that the selective generation of the Csy4/hairpin complex resulting from cleavage of target mRNA might serve as a functional poly(A)/poly(A) binding protein (PABP) surrogate, stabilizing the mRNA and supporting translation. Although the exact mechanism(s) remain to be determined, our studies expand the potential utility of CRISPR nucleases as tools for controlling mRNA stability and translation. PMID- 26354772 TI - Brain metastasis from melanoma: the prognostic value of varying sites of extracranial disease. AB - Patients with brain metastasis from melanoma have poor outcomes. Radiation is used both for prognostic and symptomatic value. We aimed to further clarify the role of stereotactic radiosurgery (SRS) and whole brain radiotherapy (WBRT) as well as the prognostic implication of various sites of extracranial disease. The records of 73 consecutive patients treated at the University of Rochester Medical Center for brain-metastatic melanoma from January 2004 to October 2013 were reviewed. The median overall survival (OS) was 3.0 months. Patients treated with WBRT alone had decreased OS compared to those treated with SRS alone (HR = 0.38, p = 0.001) or WBRT and SRS (HR = 0.51, p = 0.039). The mean number of brain metastasis differed (p = 0.002) in patients in patients who received WBRT (4.0) compared to those who did not (2.0). Among patients with extracranial disease (n = 63), bone metastasis (HR = 1.86, p = 0.047, n = 15) was a negative prognostic factor; liver (HR = 1.59, p = 0.113, n = 17), lung (HR = 1.51, p = 0.23, n = 51) and adrenal metastasis (HR = 1.70, p = 0.15, n = 10) were not. In patients with concurrent brain and lung metastasis, those with disease limited to those two sites (OS = 8.7 mo, n = 13) had improved OS (HR = 0.44, p = 0.014) compared to those with additional disease (OS = 1.8 mo, n = 50). Based on this hypothesis generating retrospective analysis, SRS may offer survival benefit compared to WBRT alone in patients with brain metastatic melanoma. Bone metastasis appears to confer a particularly poor prognosis. Those with disease confined to the lung and brain may represent a population with improved prognosis. PMID- 26354773 TI - Primary and secondary gliosarcomas: clinical, molecular and survival characteristics. AB - Gliosarcoma is classified by the World Health Organization as a variant of glioblastoma. These tumors exhibit biphasic histologic and immunophenotypic features, reflecting both glial and mesenchymal differentiation. Gliosarcomas can be further classified into primary (de novo) tumors, and secondary gliosarcomas, which are diagnosed at recurrence after a diagnosis of glioblastoma. Using a retrospective review, patients seen at MD Anderson Cancer Center between 2004 and 2014 with a pathology-confirmed diagnosis of gliosarcoma were identified. 34 patients with a diagnosis of gliosarcoma seen at the time of initial diagnosis or at recurrence were identified (24 primary gliosarcomas (PGS), 10 secondary gliosarcomas (SGS)). Molecular analysis performed on fourteen patients revealed a high incidence of TP53 mutations and, rarely, EGFR and IDH mutations. Median overall survival (OS) for all patients was 17.5 months from the diagnosis of gliosarcoma, with a progression free survival (PFS) of 6.4 months. Comparing PGS with SGS, the median OS was 24.7 and 8.95 months, respectively (from the time of sarcomatous transformation in the case of SGS). The median OS in SGS patients from the initial diagnosis of GB was 25 months, with a PFS of 10.7 months. Molecular analysis revealed a higher than expected rate of TP53 mutations in GS patients and, typical of primary glioblastoma, IDH mutations were uncommon. Though our data shows improved outcomes for both PGS and SGS when compared to the literature, this is most likely a reflection of selection bias of patients treated on clinical trials at a quaternary center. PMID- 26354774 TI - Arsenite Disrupts Zinc-Dependent TGFbeta2-SMAD Activity During Murine Cardiac Progenitor Cell Differentiation. AB - TGFbeta2 (transforming growth factor-beta2) is a key growth factor regulating epithelial to mesenchymal transition (EMT). TGFbeta2 triggers cardiac progenitor cells to differentiate into mesenchymal cells and give rise to the cellular components of coronary vessels as well as cells of aortic and pulmonary valves. TGFbeta signaling is dependent on a dynamic on and off switch in Smad activity. Arsenite exposure of 1.34 MUM for 24-48 h has been reported to disrupt Smad phosphorylation leading to deficits in TGFbeta2-mediated cardiac precursor differentiation and transformation. In this study, the molecular mechanism of acute arsenite toxicity on TGFbeta2-induced Smad2/3 nuclear shuttling and TGFbeta2-mediated cardiac EMT was investigated. A 4-h exposure to 5 MUM arsenite blocks nuclear accumulation of Smad2/3 in response to TGFbeta2 without disrupting Smad phosphorylation or nuclear importation. The depletion of nuclear Smad is restored by knocking-down Smad-specific exportins, suggesting that arsenite augments Smad2/3 nuclear exportation. The blockage in TGFbeta2-Smad signaling is likely due to the loss of Zn(2+) cofactor in Smad proteins, as Zn(2+) supplementation reverses the disruption in Smad2/3 nuclear translocation and transcriptional activity by arsenite. This coincides with Zn(2+) supplementation rescuing arsenite-mediated deficits in cardiac EMT. Thus, zinc partially protects cardiac EMT from developmental toxicity by arsenite. PMID- 26354775 TI - Dysregulation of Parkin-mediated mitophagy in thyroid Hurthle cell tumors. AB - Abnormal accumulation of defective mitochondria is the hallmark of oncocytes, which are frequently observed in thyroid Hurthle cell lesions. Autophagy is an essential cellular catabolic mechanism for the degradation of dysfunctional organelles and has been implicated in several human diseases. It is yet unknown how autophagic turnover of defective mitochondria in Hurthle cell tumors is regulated. We characterized the expression patterns of molecular markers including Beclin1, LC3, PINK1 and Parkin, which are required for autophagy or mitophagy, in human oncocytic lesions of the thyroid. To undertake mechanistic studies, we investigated autophagy and mitophagy using XTC.UC1 cells, the only in vitro model of Hurthle cell tumors. Beclin1 and LC3 were highly expressed in oncocytes of Hurthle cell tumors. XTC.UC1 showed autophagic responses to starvation and rapamycin treatment, whereas they displayed ineffective activation of mitophagy, which is triggered by the coordinated action of PINK1 and Parkin in response to CCCP. This resulted in a decreased turnover of abnormal mitochondria. The mechanisms underlying defective mitophagy and mitochondrial turnover were investigated by genetic analysis of the PARK2 gene in XTC.UC1 and Hurthle cell tumor tissues. XTC.UC1 and several tumors harbored the V380L mutation, resulting in dysfunctional autoubiquitination and decreased E3 ligase activity. Consistently, oncocytes in Hurthle cell tumors displayed comparable expression of PINK1 but decreased Parkin expression in comparison to normal thyrocytes. The introduction of wild-type Parkin sensitized XTC.UC1 to death induced by CCCP. This study provides a possible etiological basis for oncocytic formation in heterogeneous Hurthle cell tumors through insufficient mitophagy leading to ineffective turnover of aberrant mitochondria caused by dysfunctional Parkin mediated pathways of mitochondria quality control. PMID- 26354777 TI - Autophagy-mediated degradation of nuclear envelope proteins during oncogene induced senescence. AB - Cellular senescence is a largely irreversible form of cell cycle arrest triggered by various types of damage and stress, including oncogene expression (termed oncogene-induced senescence or OIS). We and others have previously demonstrated that OIS occurs in human benign lesions, acting as a potent tumor suppressor mechanism. Numerous phenotypic changes occur during OIS, both in the cytoplasm and in the nucleus. These include the activation of autophagy, a catabolic process operating in the cytoplasm and downregulation of lamin B1, a component of the nuclear lamina. However, it is unknown whether these changes relate to each other. We discovered that cells entering BRAF(V600E)- or H-RAS(G12V)-induced senescence downregulate not only lamin B1 but also lamin A, as well as several other nuclear envelope (NE) proteins, resulting in an altered NE morphology. Depletion of LMNB1 or LMNA/C was sufficient to recapitulate some OIS features, including cell cycle exit and downregulation of NE proteins. We further found that the global loss of NE proteins is a consequence of their degradation by the autophagy machinery, which occurs concomitantly with autophagy induction and increased lysosomal content and activity. Our study therefore reveals a previously unknown connection between autophagy and the disruption of NE integrity during OIS. PMID- 26354776 TI - Immunosuppression associated with chronic inflammation in the tumor microenvironment. AB - Chronic inflammation contributes to cancer development via multiple mechanisms. One potential mechanism is that chronic inflammation can generate an immunosuppressive microenvironment that allows advantages for tumor formation and progression. The immunosuppressive environment in certain chronic inflammatory diseases and solid cancers is characterized by accumulation of proinflammatory mediators, infiltration of immune suppressor cells and activation of immune checkpoint pathways in effector T cells. In this review, we highlight recent advances in our understanding of how immunosuppression contributes to cancer and how proinflammatory mediators induce the immunosuppressive microenvironment via induction of immunosuppressive cells and activation of immune checkpoint pathways. PMID- 26354778 TI - Association of gastric cancer risk factors with DNA methylation levels in gastric mucosa of healthy Japanese: a cross-sectional study. AB - Helicobacter pylori infection induces aberrant DNA methylation, and methylation levels of several specific marker genes in gastric mucosa are associated with gastric cancer risk. However, it is unclear whether gastric cancer risk factors are associated with methylation levels of marker genes in healthy individuals. We conducted a cross-sectional study of 281 Japanese cancer screenees aged 40-69 years with no history of H.pylori eradication therapy who responded to a validated food frequency questionnaire. DNA methylation levels of marker genes (miR-124a-3, EMX1 and NKX6-1) in gastric mucosa were quantified by real-time methylation-specific polymerase chain reaction. A multivariate beta regression model was used to investigate the association of pack-years of smoking and intakes of green/yellow vegetables, fruit and salt with methylation levels of marker genes. All analyses were stratified by H.pylori status. We found 2.5 to 34.1 times higher mean methylation levels among those with current H.pylori infection (n = 117) compared to those without (n = 164). After adjustment for potential confounders, we found increased levels of miR-124a-3 methylation according to pack-years of smoking and decreased levels of methylation according to green/yellow vegetable intake. We did not detect these associations among those without H.pylori infection. In conclusion, smoking habits and green/yellow vegetable intake were associated with DNA methylation levels in gastric mucosae of healthy individuals with current H.pylori infection. Our study suggests that these risk factors may modify the effect of H.pylori on methylation induction and maintenance in gastric mucosa. PMID- 26354779 TI - HPV16 E6 and E7 proteins induce a chronic oxidative stress response via NOX2 that causes genomic instability and increased susceptibility to DNA damage in head and neck cancer cells. AB - Human papillomavirus (HPV) is the causative agent of a subgroup of head and neck cancer characterized by an intrinsic radiosensitivity. HPV initiates cellular transformation through the activity of E6 and E7 proteins. E6 and E7 expression is necessary but not sufficient to transform the host cell, as genomic instability is required to acquire the malignant phenotype in HPV-initiated cells. This study reveals a key role played by oxidative stress in promoting genomic instability and radiosensitivity in HPV-positive head and neck cancer. By employing an isogenic human cell model, we observed that expression of E6 and E7 is sufficient to induce reactive oxygen species (ROS) generation in head and neck cancer cells. E6/E7-induced oxidative stress is mediated by nicotinamide adenine dinucleotide phosphate oxidases (NOXs) and causes DNA damage and chromosomal aberrations. This mechanism for genomic instability distinguishes HPV-positive from HPV-negative tumors, as we observed NOX-induced oxidative stress in HPV positive but not HPV-negative head and neck cancer cells. We identified NOX2 as the source of HPV-induced oxidative stress as NOX2 silencing significantly reduced ROS generation, DNA damage and chromosomal aberrations in HPV-positive cells. Due to their state of chronic oxidative stress, HPV-positive cells are more susceptible to DNA damage induced by ROS and ionizing radiation (IR). Furthermore, exposure to IR results in the formation of complex lesions in HPV positive cells as indicated by the higher amount of chromosomal breakage observed in this group of cells. These results reveal a novel mechanism for sustaining genomic instability in HPV-positive head and neck tumors and elucidate its contribution to their intrinsic radiosensitivity. PMID- 26354781 TI - An Adolescent With Cough and Dyspepsia. PMID- 26354780 TI - Interactions of DNA repair gene variants modulate chromosomal aberrations in healthy subjects. AB - Human cancers are often associated with numerical and structural chromosomal instability. Structural chromosomal aberrations (CAs) in peripheral blood lymphocytes (PBL) arise as consequences of direct DNA damage or due to replication on a damaged DNA template. In both cases, DNA repair is critical and inter-individual differences in its capacity are probably due to corresponding genetic variations. We investigated functional variants in DNA repair genes (base and nucleotide excision repair, double-strand break repair) in relation to CAs, chromatid-type aberrations (CTAs) and chromosome-type aberrations (CSAs) in healthy individuals. Chromosomal damage was determined by conventional cytogenetic analysis. The genotyping was performed by both restriction fragment length polymorphism and TaqMan allelic discrimination assays. Multivariate logistic regression was applied for testing individual factors on CAs, CTAs and CSAs. Pair-wise genotype interactions of 11 genes were constructed for all possible pairs of single-nucleotide polymorphisms. Analysed individually, we observed significantly lower CTA frequencies in association with XPD Lys751Gln homozygous variant genotype [odds ratio (OR) 0.64, 95% confidence interval (CI) 0.48-0.85, P = 0.004; n = 1777]. A significant association of heterozygous variant genotype in RAD54L with increased CSA frequency (OR 1.96, 95% CI 1.01 4.02, P = 0.03) was determined in 282 subjects with available genotype. By addressing gene-gene interactions, we discovered 14 interactions significantly modulating CAs, 9 CTAs and 12 CSAs frequencies. Highly significant interactions included always pairs from two different pathways. Although individual variants in genes encoding DNA repair proteins modulate CAs only modestly, several gene gene interactions in DNA repair genes evinced either enhanced or decreased CA frequencies suggesting that CAs accumulation requires complex interplay between different DNA repair pathways. PMID- 26354782 TI - Special issue on Regulation of the Photosynthetic Systems in honor of Tingyun Kuang. PMID- 26354783 TI - The Thrill Is Gone: A Case of Progressive Dyspnea. PMID- 26354784 TI - ECG Response: September 8, 2015. PMID- 26354785 TI - Granulomatosis With Polyangiitis Presenting With an Intracardiac Mass and Complete Heart Block: Enhanced Images by 3-Dimensional Echocardiography. PMID- 26354786 TI - Shock After Successful Primary Percutaneous Coronary Intervention for Ventricular Fibrillation. PMID- 26354787 TI - Cardiac Sarcoidosis. PMID- 26354788 TI - Letter by Gonzalez-Salvado et al Regarding Article, "Extravirgin Olive Oil Consumption Reduces Risk of Atrial Fibrillation: The PREDIMED (Prevencion con Dieta Mediterranea) Trial". PMID- 26354789 TI - Response to Letter Regarding Article, "Extravirgin Olive Oil Consumption Reduces Risk of Atrial Fibrillation: The PREDIMED (Prevencion con Dieta Mediterranea) Trial". PMID- 26354790 TI - Benefits of combinative application of probiotic, enterocin M-producing strain Enterococcus faecium AL41 and Eleutherococcus senticosus in rabbits. AB - This study presents the effects of the probiotic and enterocin M-producing strain Enterococcus faecium AL41 on microbiota, phagocytic activity (PA), oxidative stress, performance and biochemical parameters when applied individually or in combination with Eleutherococcus senticosus in rabbits. The novelty of the study lies in the use of our non-rabbit-derived strain (AL41 = CCM8558) which produces new enterocin M. Ninety-six post-weaned rabbits (Hyplus breed) aged 5 weeks were divided into three experimental groups, 24 in each: E. senticosus (ES, 30 g/100 kg) in feed, E. faecium AL41 (10(9) CFU/mL marked by rifampicin to differentiate it from other enterococci) in water, and ES + AL. AL41 colonized sufficiently in rabbits to reduce coliforms, staphylococci, pseudomonads and clostridia. Slight decrease in bacteria was also found in the caecum and appendix. Phagocytic activity was significantly increased in the experimental groups compared to the control group (CG) (p < 0.001; p < 0.05). Applications did not evoke oxidative stress. Biochemical parameters in blood and caecal organic acids were slightly influenced. Average daily weight gain was slightly higher in ES and AL + ES. Combinative application of E. faecium with E. senticosus can be beneficial in rabbits. AL41 strain alone and in combination with ES produced reduction in spoilage bacteria; the highest stimulation of PA was in the AL41 + ES group. PMID- 26354792 TI - Leprosy-related mortality in Brazil: a neglected condition of a neglected disease. AB - BACKGROUND: Leprosy is a public health problem and a neglected condition of morbidity and mortality in several countries of the world. We analysed time trends and spatiotemporal patterns of leprosy-related mortality in Brazil. METHODS: We performed a nationwide population-based study using secondary mortality data. We included all deaths that occurred in Brazil between 2000 and 2011, in which leprosy was mentioned in any field of death certificates. RESULTS: Leprosy was identified in 7732/12 491 280 deaths (0.1%). Average annual age adjusted mortality rate was 0.43 deaths/100 000 inhabitants (95% CI 0.40-0.46). The burden of leprosy deaths was higher among males, elderly, black race/colour and in leprosy-endemic regions. Lepromatous leprosy was the most common clinical form mentioned. Mortality rates showed a significant nationwide decrease over the period (annual percent change [APC]: -2.8%; 95% CI -4.2 to -2.4). We observed decreasing mortality rates in the South, Southeast and Central-West regions, while the rates remained stable in North and Northeast regions. Spatial and spatiotemporal high-risk clusters for leprosy-related deaths were distributed mainly in highly endemic and socio-economically deprived regions. CONCLUSIONS: Leprosy is a neglected cause of death in Brazil since the disease is preventable, and a cost-effective treatment is available. Sustainable control measures should include appropriate management and systematic monitoring of leprosy-related complications, such as severe leprosy reactions and adverse effects to multidrug therapy. PMID- 26354791 TI - Continuous co-production of ethanol and xylitol from rice straw hydrolysate in a membrane bioreactor. AB - The present study was set to develop a robust and economic biorefinery process for continuous co-production of ethanol and xylitol from rice straw in a membrane bioreactor. Acid pretreatment, enzymatic hydrolysis, detoxification, yeast strains selection, single and co-culture batch fermentation, and finally continuous co-fermentation were optimized. The combination of diluted acid pretreatment (3.5 %) and enzymatic conversion (1:10 enzyme (63 floating-point unit (FPU)/mL)/biomass ratio) resulted in the maximum sugar yield (81 % conversion). By concentrating the hydrolysates, sugars level increased by threefold while that of furfural reduced by 50 % (0.56 to 0.28 g/L). Combined application of active carbon and resin led to complete removal of furfural, hydroxyl methyl furfural, and acetic acid. The strains Saccharomyces cerevisiae NCIM 3090 with 66.4 g/L ethanol production and Candida tropicalis NCIM 3119 with 9.9 g/L xylitol production were selected. The maximum concentrations of ethanol and xylitol in the single cultures were recorded at 31.5 g/L (0.42 g/g yield) and 26.5 g/L (0.58 g/g yield), respectively. In the batch co-culture system, the ethanol and xylitol productions were 33.4 g/L (0.44 g/g yield) and 25.1 g/L (0.55 g/g yield), respectively. The maximum ethanol and xylitol volumetric productivity values in the batch co-culture system were 65 and 58 % after 25 and 60 h, but were improved in the continuous co-culture mode and reached 80 % (55 g/L) and 68 % (31 g/L) at the dilution rate of 0.03 L per hour, respectively. Hence, the continuous co-production strategy developed in this study could be recommended for producing value-added products from this hugely generated lignocellulosic waste. PMID- 26354793 TI - Molecular and culture-based diagnosis of Clostridium difficile isolates from Cote d'Ivoire after prolonged storage at disrupted cold chain conditions. AB - BACKGROUND: Although Clostridium difficile is a major cause of diarrhoea, its epidemiology in tropical settings is poorly understood. Strain characterisation requires work-up in specialised laboratories, often after prolonged storage without properly maintained cold chain. METHODS: We screened 298 human faecal samples from Cote d'Ivoire using a rapid test for C. difficile glutamate dehydrogenase (GDH). GDH-positive samples were aerobically stored at disrupted cold chain conditions (mean duration: 11 days) before transfer to a reference laboratory for anaerobic culture, susceptibility testing, PCR assays and ribotyping. RESULTS: Sixteen samples (5.4%) had a positive GDH screening test. C. difficile infection was confirmed in six specimens by culture and PCR, while no nucleic acids of C. difficile were detected in the culture-negative samples. Further analysis of stool samples harbouring toxigenic C. difficile strains confirmed that both GDH and toxins remained detectable for at least 28 days, regardless of storage conditions (aerobic storage at 4 degrees C or 20 degrees C). CONCLUSIONS: Storage conditions only minimally affect recovery of C. difficile and its toxins in stool culture. A rapid GDH screening test and subsequent transfer of GDH-positive stool samples to reference laboratories for in-depth characterisation may improve our understanding of the epidemiology of C. difficile in the tropics. PMID- 26354794 TI - Case report of severe Cushing's syndrome in medullary thyroid cancer complicated by functional diabetes insipidus, aortic dissection, jejunal intussusception, and paraneoplastic dysautonomia: remission with sorafenib without reduction in cortisol concentration. AB - BACKGROUND: Normalization of cortisol concentration by multikinase inhibitors have been reported in three patients with medullary thyroid cancer-related Cushing's syndrome. Aortic dissection has been reported in three patients with Cushing's syndrome. Diabetes insipidus without intrasellar metastasis, intestinal intussusception, and paraneoplastic dysautonomia have not been reported in medullary thyroid cancer. CASE PRESENTATION: An adult male with metastatic medullary thyroid cancer presented with hyperglycemia, hypernatremia, hypokalemia, hypertension, acne-like rash, and diabetes insipidus (urine volume >8 L/d, osmolality 190 mOsm/kg). Serum cortisol, adrenocorticoitropic hormone, dehydroepiandrostenedione sulfate, and urinary free cortisol were elevated 8, 20, 4.4, and 340 folds, respectively. Pituitary imaging was normal. Computed tomography scan revealed jejunal intussusception and incidental abdominal aortic dissection. Sorafenib treatment was associated with Cushing's syndrome remission, elevated progesterone (>10 fold), normalization of dehydroepiandrostenedione sulfate, but persistently elevated cortisol concentration. Newly-developed proximal lower limb weakness and decreased salivation were associated with elevated ganglionic neuronal acetylcholine receptor (alpha-3) and borderline P/Q type calcium channel antibodies. CONCLUSION: Extreme cortisol concentration may have contributed to aortic dissection and suppressed antidiuretic hormone secretion; which combined with hypokalemia due cortisol activation of mineralocorticoid receptors, manifested as diabetes insipidus. This is the first report of paraneoplastic dysautonomia and jejunal intussusception in medullary thyroid cancer, they may be related to medullary thyroid cancer's neuroendocrine origin and metastasis, respectively. Remission of Cushing's syndrome without measurable reduction in cortisol concentration suggests a novel cortisol independent mechanism of action or assay cross-reactivity. Normalization of dehydroepiandrostenedione sulfate and elevation of progesterone suggest inhibition of 17-hydroxylase and 21-hydroxylase activities by sorafenib. PMID- 26354795 TI - A novel genus in the order Picornavirales detected in human stool. AB - Recently, four new viruses belonging to an unassigned family within the order Picornavirales were identified in excrements of healthy carp (fisavirus) and pigs (posavirus 1, 2 and 3). We report the detection and characterization of a fifth virus present in human faeces. The virus, named human stool-associated RNA virus (husavirus), contains a single ORF encoding a putative 2993 AA polyprotein, with a Hel-Pro-Pol replication block, typical for the Picornavirales. Phylogenetic analysis revealed that the closest relative to husavirus is posavirus 1, and together they cluster with fisavirus, posavirus 2 and 3 and a roundworm (Ascaris suum) derived virus. Husavirus was detected in eight human stool samples collected in 1984 (n52), 1985 (n54), 1995 (n51) and 2014 (n51). From three strains of husavirus from 1984 and 1985 the full genome sequence was determined, showing less than 5% intraspecies variation in the nucleotide composition. The host of this virus remains to be determined. PMID- 26354796 TI - Boronic prodrug of 4-hydroxytamoxifen is more efficacious than tamoxifen with enhanced bioavailability independent of CYP2D6 status. AB - BACKGROUND: Poor initial response to tamoxifen due to CYP2D6 polymorphism and adverse side effects are two clinical challenges in tamoxifen therapy. We report the development and preclinical testing of a boronic prodrug to orally deliver 4 OHT at therapeutically effective concentrations but at a fraction of the standard tamoxifen dose. METHODS: A mouse xenograft tumor model was used to investigate the efficacy of ZB497 in comparison with tamoxifen. Pharmacokinetic studies were conducted to evaluate the metabolism and bioavailability of the drug in mice. Drug and metabolites distribution in xenograft tumor tissues was determined by high performance liquid chromatography-tandem mass spectrometry. RESULTS: The boronic prodrug, ZB497, can not only be efficiently converted to 4-OHT in mice, but also afforded over 30 fold higher plasma concentrations of 4-OHT than in mice given either the same dose of 4-OHT or tamoxifen. Further, ZB497 was more effective than tamoxifen at lowered dosage in inhibiting the growth of xenograft tumors in mice. Consistent with these observations, ZB497 treated mice accumulated over 6 times higher total drug concentrations than tamoxifen treated mice. CONCLUSIONS: Our study demonstrates that ZB497 effectively delivers a markedly increased plasma concentration of 4-OHT in mice. The boronic prodrug was shown to have far superior bioavailability of 4-OHT compared to tamoxifen or 4 OHT administration as measured by the area under the plasma concentration time curve (AUC), plasma peak concentrations, and drug accumulation in tumor tissues. Further, ZB497 proves to be a more efficacious hormone therapy than tamoxifen administered at a reduced dose in mice. PMID- 26354797 TI - Efficacy of Biological-Targeted Treatments in Takayasu Arteritis: Multicenter, Retrospective Study of 49 Patients. AB - BACKGROUND: The goal of this work was to assess the safety and efficacy of biologics (ie, tumor necrosis factor-alpha antagonists and tocilizumab) in patients with Takayasu arteritis. METHODS AND RESULTS: This was a retrospective, multicenter study of the characteristics and outcomes of 49 patients with Takayasu arteritis (80% female; median age, 42 years [20-55 years] treated by tumor necrosis factor-alpha antagonists [80%] or tocilizumab [20%]) and fulfilling American College of Rheumatology or Ishikawa criteria. Factors associated with complete response were assessed. Eighty-eight percent of patients with Takayasu arteritis were inadequately controlled with or were intolerant to conventional immunosuppressive therapy (median number, 3 [1-5]). Overall response (ie, complete and partial) to biological-targeted treatments at 6 and 12 months was 75% and 83%, respectively. There were significantly lower C-reactive protein levels at the initiation of biological-targeted treatments (22 mg/L [10-46 mg/L] versus 58 mg/L [26-76 mg/L]; P=0.006) and a trend toward fewer immunosuppressants drugs used before biologics (P=0.054) in responders (ie, complete or partial responders) relative to nonresponders to biological-targeted treatments. C reactive protein levels and daily prednisone dose significantly decreased after 12 months of biological-targeted treatments (30 versus 6 mg/L [P<0.05] and 15 versus 7.5 mg [P<0.05] at baseline and 12 months, respectively). The 3-year relapse-free survival was 90.9% (83.5%-99%) over the biological treatment period compared with 58.7% (43.3%-79.7%; P=0.0025) with disease-modifying antirheumatic drugs. No difference in efficacy was found between tumor necrosis factor-alpha antagonists and tocilizumab. After a median follow-up of 24 months (2-95 months), 21% of patients experienced adverse effects, with biological-targeted treatments discontinued in 6.6% of cases. CONCLUSION: This nationwide study shows a high efficacy of biological-targeted treatments in refractory patients with Takayasu arteritis with an acceptable safety profile. PMID- 26354798 TI - Takayasu Arteritis: It Is Time to Work Together. PMID- 26354799 TI - Current Clinical Features of New Patients With Takayasu Arteritis Observed From Cross-Country Research in Japan: Age and Sex Specificity. AB - BACKGROUND: The clinical features of newly diagnosed Japanese patients with Takayasu arteritis and its age or sex specificities are unknown. METHODS AND RESULTS: We analyzed information from nationwide registration forms submitted by patients with Takayasu arteritis between April 2001 and March 2011 as part of a research program by the Japanese Ministry of Health, Labor and Welfare. Among the 7779 patients who submitted their forms, 1372 newly registered patients with Takayasu arteritis were enrolled; 83.8% were female. The median age at onset was 35 years, which was significantly higher in male patients (median, 43.5 years) than in female patients (median, 34 years; P<0.001). Local symptoms and findings were most commonly observed in the cervicobrachial area, with more complaints in the head or neck than in the upper limbs. Approximately 85% of the patients had vascular involvements in the aortic arch or its major branches; many young female patients had localized lesions. Although male patients had extensive aortic lesions or aneurysms with more complications, localized abdominal lesions were relatively more frequent in male patients with age at onset >40 years than in other age-sex groups. Disease statuses were severe in patients who registered at >=1 year after onset. CONCLUSIONS: The proportions of male patients and patients with elderly onset increased in newly diagnosed patients with Takayasu arteritis. Their clinical and angiographic features differed according to onset age and sex. PMID- 26354800 TI - Interaction of obesity and infections. AB - There is evidence that certain infections may induce obesity. Obese persons may also have more severe infections and have compromised response to therapies. The objective of this study is to review the available literature identifying infections that potentially contribute to greater body mass index (BMI) and differential responses of overweight and obese persons to infections. A systematic literature review of human studies examining associations between infections and weight gain, differential susceptibility, severity, and response to prevention and treatment of infection according to BMI status (January 1980 July 2014) was conducted. Three hundred and forty-three studies were eligible for inclusion. Evidence indicated that viral infection by human adenovirus Ad36 and antibiotic eradication of Helicobacter pylori were followed by weight gain. People who were overweight or obese had higher susceptibility to developing post surgical infections, H1N1 influenza and periodontal disease. More severe infections tended to be present in people with a larger BMI. People with a higher BMI had a reduced response to vaccinations and antimicrobial drugs. Higher doses of antibiotics were more effective in obese patients. Infections may influence BMI, and BMI status may influence response to certain infections, as well as to preventive and treatment measures. These observations have potential clinical implications. PMID- 26354801 TI - Novel Nanostructured Solid Materials for Modulating Oral Drug Delivery from Solid State Lipid-Based Drug Delivery Systems. AB - Lipid-based drug delivery systems (LBDDS) have gained significant attention in recent times, owing to their ability to overcome the challenges limiting the oral delivery of poorly water-soluble drugs. Despite the successful commercialization of several LBDDS products over the years, a large discrepancy exists between the number of poorly water-soluble drugs displaying suboptimal in vivo performances and the application of LBDDS to mitigate their various delivery challenges. Conventional LBDDS, including lipid solutions and suspensions, emulsions, and self-emulsifying formulations, suffer from various drawbacks limiting their widespread use and commercialization. Accordingly, solid-state LBDDS, fabricated by adsorbing LBDDS onto a chemically inert solid carrier material, have attracted substantial interest as a viable means of stabilizing LBDDS whilst eliminating some of the various limitations. This review describes the impact of solid carrier choice on LBDDS performance and highlights the importance of appropriate solid carrier material selection when designing hybrid solid-state LBDDS. Specifically, emphasis is placed on discussing the ability of the specific solid carrier to modulate drug release, control lipase action and lipid digestion, and enhance biopharmaceutical performance above the original liquid-state LBDDS. To encourage the interested reader to consider their solid carrier choice on a higher level, various novel materials with the potential for future use as solid carriers for LBDDS are described. This review is highly significant in guiding future research directions in the solid-state LBDDS field and fostering the translation of these delivery systems to the pharmaceutical marketplace. PMID- 26354803 TI - The Parmotrema acid test: a look at species delineation in the P. perforatum group 40 y later. AB - Parmotrema perforatum and its relatives form a morphologically distinctive group of species, most of which are common and endemic to eastern North America. Species delimitation in this ecologically important group was the subject of extensive inquiry before the advent of molecular systematics and computationally intensive niche modeling. As part of a large-scale lichen biodiversity inventory of the Mid-Atlantic Coastal Plain, we used ITS sequence data to examine the utility of characters (morphological, chemical, reproductive, ecological) in circumscribing four species in this group (P. hypoleucinum, P. hypotropum, P. perforatum, P. subrigidum). We found that P. hypoleucinum and P. subrigidum as currently circumscribed are monophyletic and the latter comprises two chemotypes differing in the presence or absence of norstictic acid in addition to alectoronic acid. The sequences of P. hypotropum and P. perforatum, which are chemically identical species and differ only in reproductive mode, were intermixed in a single, well-supported clade. The two chemotypes of P. subrigidum are partially allopatric and their sequences are >99% identical. Nonetheless, niche modeling suggests they occupy significantly different ecological niches. These results provide a new perspective on much-debated questions on species circumscription in lichens and suggest new avenues for genetic, ecological and systematic research. PMID- 26354802 TI - Fetal Sex and RHD Genotyping with Digital PCR Demonstrates Greater Sensitivity than Real-time PCR. AB - BACKGROUND: Noninvasive genotyping of fetal RHD (Rh blood group, D antigen) can prevent the unnecessary administration of prophylactic anti-D to women carrying RHD-negative fetuses. We evaluated laboratory methods for such genotyping. METHODS: Blood samples were collected in EDTA tubes and Streck(r) Cell-Free DNATM blood collection tubes (Streck BCTs) from RHD-negative women (n = 46). Using Y specific and RHD-specific targets, we investigated variation in the cell-free fetal DNA (cffDNA) fraction and determined the sensitivity achieved for optimal and suboptimal samples with a novel Droplet DigitalTM PCR (ddPCR) platform compared with real-time quantitative PCR (qPCR). RESULTS: The cffDNA fraction was significantly larger for samples collected in Streck BCTs compared with samples collected in EDTA tubes (P < 0.001). In samples expressing optimal cffDNA fractions (>=4%), both qPCR and digital PCR (dPCR) showed 100% sensitivity for the TSPY1 (testis-specific protein, Y-linked 1) and RHD7 (RHD exon 7) assays. Although dPCR also had 100% sensitivity for RHD5 (RHD exon 5), qPCR had reduced sensitivity (83%) for this target. For samples expressing suboptimal cffDNA fractions (<2%), dPCR achieved 100% sensitivity for all assays, whereas qPCR achieved 100% sensitivity only for the TSPY1 (multicopy target) assay. CONCLUSIONS: qPCR was not found to be an effective tool for RHD genotyping in suboptimal samples (<2% cffDNA). However, when testing the same suboptimal samples on the same day by dPCR, 100% sensitivity was achieved for both fetal sex determination and RHD genotyping. Use of dPCR for identification of fetal specific markers can reduce the occurrence of false-negative and inconclusive results, particularly when samples express high levels of background maternal cell-free DNA. PMID- 26354804 TI - Molecular phylogenetics and taxonomy of the Calvitimela aglaea complex (Tephromelataceae, Lecanorales). AB - Contributing to the process of reassigning lecideoid lichens to natural taxa, we assessed phylogenetic relationships and species delimitation in the Calvitimela aglaea complex (Tephromelataceae) using DNA sequence data and morphological/anatomical and chemical characters. Phylogenetic analysis of nuclear (ITS, MCM7, TEF1-alpha) and mitochondrial (ribosomal SSU) DNA sequences revealed Mycoblastus as sister to a strongly supported clade comprising Calvitimela, Tephrolema and Violella. Species of these three genera fall into six strongly supported subclades with low backbone resolution. Two of these are represented by Tephromela and Violella, which are readily circumscribed morphologically. The remaining four subclades encompass lineages that have until now been assigned to Calvitimela. While Tephromela and Violella as currently circumscribed are recovered as monophyletic in our analyses, Calvitimela is paraphyletic, with four deeply divergent clades. We recognize these four clades as subgenera Calomela, Calvitimela, Paramela and Severidea. Our molecular results further support the recognition of two recently discovered sterile crusts as new species, Calvitimela cuprea and C. livida, distinguished from previously known species by their production of asexual diaspores and from each other by secondary metabolite chemistry. We also report Calvitimela perlata as new for continental North America. PMID- 26354805 TI - Two new species of Thyronectria from Mediterranean Europe. AB - Two new species of Thyronectria growing in Mediterranean vegetation are described from southern Spain; they are T. giennensis from Quercus ilex ssp. rotundifolia and T. pistaciae from Pistacia lentiscus. Both species are characterized by morphology of sexual and asexual morphs and by DNA data. They have olivaceous to green-brown muriform ascospores and are closely related to T. asturiensis and T. roseovirens, as determined by multigene phylogenetic analyses of a matrix containing six loci (ITS and 28S regions of nuc rDNA, ACT1, RPB1, RPB2, TEF1 and TUB2 genes). We also report that Cucurbitaria bicolor is a synonym of Thyronectria rhodochlora, the type species of Thyronectria. PMID- 26354806 TI - The human gut mycobiome: pitfalls and potentials--a mycologist's perspective. AB - We have entered the Age of the Microbiome, with new studies appearing constantly and whole journals devoted to the human microbiome. While bacteria outnumber other gut microbes by orders of magnitude, eukaryotes are consistently found in the human gut and are represented primarily by the fungi. Compiling 36 studies 1917-2015 we found at least 267 distinct fungal taxa have been reported from the human gut, and seemingly every new study includes one or more fungi not previously described from this niche. This diversity, while impressive, is illusory. If we examine gut fungi, we will quickly observe a division between a small number of commonly detected species (Candida yeasts, Saccharomyces and yeasts in the Dipodascaceae, and Malassezia species) and a long tail of taxa that have been reported only once. Furthermore, an investigation into the ecology of these rare species reveals that many of them are incapable of colonization or long-term persistence in the gut. This paper examines what we know and have yet to learn about the fungal component of the gut microbiome, or "mycobiome", and an overview of methods. We address the potential of the field while introducing some caveats and argue for the necessity of including mycologists in mycobiome studies. PMID- 26354807 TI - The genus Hebeloma in the alpine belt of the Carpathians including two new species. AB - Between 2002 and 2012 regular visits to the Carpathians were made and a number of Hebeloma spp. were collected from the alpine area. In total 44 collections were made that represent 11 species, two of which, Hebeloma grandisporum and H. oreophilum, are described here as new. Of the 11 species, four (H. alpinum, H. marginatulum and the two species described as new) are known only from alpine or Arctic habitats. Hebeloma dunense and H. mesophaeum are commonly found in, but not restricted to, alpine habitats. The other five species (H. aanenii, H. laterinum, H. naviculosporum, H. vaccinum, H. velutipes) are usually found in lowland or boreal habitats. Hebeloma naviculosporum is reported for the first time from the alpine zone and H. alpinum for the first time as growing with Helianthemum. All but two species (H. alpinum, H. marginatulum) are reported for the first time from the Carpathian alpine zone. In this paper we discuss the habitat, the 11 recorded species and give detailed descriptions of the two new species, both morphologically and molecularly. A key for Hebeloma species from sect. Hebeloma occurring in Arctic-alpine habitats is provided. PMID- 26354808 TI - The genus Cryptosphaeria in the western United States: taxonomy, multilocus phylogeny and a new species, C. multicontinentalis. AB - This study investigates the diversity and taxonomy of Cryptosphaeria species occurring in the western United States on the basis of morphological characters and multilocus phylogenetic analyses of the ribosomal internal transcribed spacer region, parts of a beta-tubulin gene, the DNA-dependent RNA polymerase II second largest subunit gene and the nuclear ribosomal large subunit gene. Cryptosphaeria multicontinentalis sp. nov is described from the Sierra Nevada and central coast of California on Populus tremuloides, P. balsamifera subsp. trichocarpa and P. fremontii. Cryptosphaeria pullmanensis is reported from a wide geographic area in the western United States on the main host, P. fremontii. The pathogen C. lignyota is reported for the first time from the Sierra Nevada of California on P. tremuloides. The phylogenetic analyses showed that C. multicontinentalis is a sister species to C. lignyota. Both species were closely related to C. subcutanea and more distantly related to C. pullmanensis. Characteristics of both teleomorph and anamorph of the newly introduced species C. multicontinentalis are described and illustrated. PMID- 26354809 TI - Clinical Significance and Characterization of Streptococcus tigurinus Isolates in an Adult Population. AB - Streptococcus tigurinus is a newly described member of the Streptococcus mitis group. Due to the difficulty in distinguishing viridans group streptococci (VGS) by phenotype, analysis of 16S rRNA sequences is necessary for the accurate identification of most species. Through a laboratory policy of analyzing all clinically significant isolates from the VGS group by16S rRNA gene sequencing, we identified 14 S. tigurinus isolates from 11 patients. The Vitek 2 system most commonly gave an excellent rating to an incorrect identification (e.g., Streptococcus mitis), as did matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) (e.g., Streptococcus oralis). S. tigurinus strains were recovered from numerous body sites, including the blood, peritoneal fluid, bone, synovial fluid, a perianal abscess, and an arm wound. Retrospective chart review indicated that most isolates were clinically significant, with bacteremia (n = 5), soft tissue infections (n = 3) osteomyelitis (n = 2), infected joint prosthesis (n = 2), and peritonitis (n = 2) being the most common, thus expanding the spectrum of disease associated with S. tigurinus. PMID- 26354810 TI - Molecular Testing for Plasmodium falciparum by Use of Serum or Plasma and Comparison with Microscopy and Rapid Diagnostic Testing in Febrile Nigerian Patients. AB - Plasmodium nucleic acids have been detected in serum and plasma, but there is little published data describing the diagnostic performance of malaria nucleic acid amplification tests (NAATs) using these specimen types. Previously, our group described a multiplex NAAT for the detection of dengue virus, Leptospira, and Plasmodium species with a callout for P. falciparum (the DLM assay) that demonstrated sensitive detection of P. falciparum from plasma samples during initial evaluation. In this study, we evaluated the sensitivity and specificity of P. falciparum detection in febrile Nigerian patients using the DLM assay, microscopy, and a rapid diagnostic test (BinaxNOW Malaria). Assay performances were compared using a composite reference, which was considered positive if malaria was detected by two or more methods. Serum (n = 182) or plasma (n = 148) from 317 patients was tested; the average sample volume was 70 MUl (range, 5 to 300 MUl). The sensitivity and specificity of the DLM assay were 97.1% and 93.5%, respectively. The sensitivity of the malaria rapid diagnostic test (98.1%) was similar to that of the DLM assay, and both proved significantly more sensitive than microscopy (79%; P < 0.0001). When analysis was limited to samples with >=75 MUl of serum or plasma, the sensitivity of the DLM assay improved to 99% and specificity was 97.5%. For P. falciparum cases, cycle threshold values in the DLM assay correlated with the parasite density detected by microscopy (Spearman's rank correlation coefficient, P < 0.0001). In conclusion, malaria detection using the DLM assay on serum or plasma is more sensitive than and equal in specificity to microscopy in patients with P. falciparum malaria. PMID- 26354811 TI - Molecular Characterization of a Catalase-Negative Staphylococcus aureus Blood Culture Isolate. AB - Here we report a catalase-negative methicillin-sensitive Staphylococcus aureus isolate collected from a blood culture. Sequencing through the gene encoding catalase, katA, demonstrated a 2-bp insertion. The resulting frameshift mutation generates a protein that has lost 26 amino acids (aa) at its C-terminal domain. PMID- 26354812 TI - Infection with Toxin A-Negative, Toxin B-Negative, Binary Toxin-Positive Clostridium difficile in a Young Patient with Ulcerative Colitis. AB - Large clostridial toxin-negative, binary toxin-positive (A(-) B(-) CDT(+)) strains of Clostridium difficile are almost never associated with clinically significant C. difficile infection (CDI), possibly because such strains are not detected by most diagnostic methods. We report the isolation of an A(-) B(-) CDT(+) ribotype 033 (RT033) strain of C. difficile from a young patient with ulcerative colitis and severe diarrhea. PMID- 26354813 TI - Haemophilus influenzae with Non-Beta-Lactamase-Mediated Beta-Lactam Resistance: Easy To Find but Hard To Categorize. AB - Haemophilus influenzae is a major pathogen, and beta-lactams are first-line drugs. Resistance due to altered penicillin-binding protein 3 (rPBP3) is frequent, and susceptibility testing of such strains is challenging. A collection of 154 beta-lactamase-negative isolates with a large proportion of rPBP3 (67.5%) was used to evaluate and compare Etest (Haemophilus test medium [HTM]) and disk diffusion (EUCAST method) for categorization of susceptibility to aminopenicillins and cefuroxime, using MICs generated with broth (HTM) microdilution and clinical breakpoints from CLSI and EUCAST as the gold standards. In addition, the proficiency of nine disks in screening for the rPBP3 genotype (N526K positive) was evaluated. By Etest, both essential and categorical agreement were generally poor (<70%), with high very major errors (VME) (CLSI, 13.0%; EUCAST, 34.3%) and falsely susceptible rates (FSR) (CLSI, 87.0%; EUCAST, 88.3%) for ampicillin. Ampicillin (2 MUg) with adjusted (+2 mm) zone breakpoints was superior to Etest for categorization of susceptibility to ampicillin (agreement, 74.0%; VME, 11.0%; FSR, 28.3%). Conversely, Etest was superior to 30 MUg cefuroxime for categorization of susceptibility to cefuroxime (agreement, 57.1% versus 60.4%; VME, 2.6% versus 9.7%; FSR, 7.1% versus 26.8%). Benzylpenicillin (1 unit) (EUCAST screening disk) and cefuroxime (5 MUg) identified rPBP3 isolates with highest accuracies (95.5% and 92.2%, respectively). In conclusion, disk screening reliably detects rPBP3 H. influenzae, but false ampicillin susceptibility is frequent with routine methods. We suggest adding a comment recommending high-dose aminopenicillin therapy or the use of other agents for severe infections with screening-positive isolates that are susceptible to aminopenicillins by gradient or disk diffusion. PMID- 26354814 TI - Usefulness of Adjunctive Fecal Calprotectin and Serum Procalcitonin in Individuals Positive for Clostridium difficile Toxin Gene by PCR Assay. AB - In 54/64 subjects with nosocomial diarrhea, fecal calprotectin levels correlated with the results of stool samples tested for Clostridium difficile toxin gene by PCR. Fecal calprotectin levels can be used as an adjunctive measure to PCR to support the diagnosis of C. difficile infection. PMID- 26354815 TI - Utility of Whole-Genome Sequencing of Escherichia coli O157 for Outbreak Detection and Epidemiological Surveillance. AB - Detailed laboratory characterization of Escherichia coli O157 is essential to inform epidemiological investigations. This study assessed the utility of whole genome sequencing (WGS) for outbreak detection and epidemiological surveillance of E. coli O157, and the data were used to identify discernible associations between genotypes and clinical outcomes. One hundred five E. coli O157 strains isolated over a 5-year period from human fecal samples in Lothian, Scotland, were sequenced with the Ion Torrent Personal Genome Machine. A total of 8,721 variable sites in the core genome were identified among the 105 isolates; 47% of the single nucleotide polymorphisms (SNPs) were attributable to six "atypical" E. coli O157 strains and included recombinant regions. Phylogenetic analyses showed that WGS correlated well with the epidemiological data. Epidemiological links existed between cases whose isolates differed by three or fewer SNPs. WGS also correlated well with multilocus variable-number tandem repeat analysis (MLVA) typing data, with only three discordant results observed, all among isolates from cases not known to be epidemiologically related. WGS produced a better-supported, higher-resolution phylogeny than MLVA, confirming that the method is more suitable for epidemiological surveillance of E. coli O157. A combination of in silico analyses (VirulenceFinder, ResFinder, and local BLAST searches) were used to determine stx subtypes, multilocus sequence types (15 loci), and the presence of virulence and acquired antimicrobial resistance genes. There was a high level of correlation between the WGS data and our routine typing methods, although some discordant results were observed, mostly related to the limitation of short sequence read assembly. The data were used to identify sublineages and clades of E. coli O157, and when they were correlated with the clinical outcome data, they showed that one clade, Ic3, was significantly associated with severe disease. Together, the results show that WGS data can provide higher resolution of the relationships between E. coli O157 isolates than that provided by MLVA. The method has the potential to streamline the laboratory workflow and provide detailed information for the clinical management of patients and public health interventions. PMID- 26354816 TI - Diagnostic Accuracy of Rapid Antigen Detection Tests for Respiratory Syncytial Virus Infection: Systematic Review and Meta-analysis. AB - Respiratory syncytial virus (RSV) rapid antigen detection tests (RADT) are extensively used in clinical laboratories. We performed a systematic review and meta-analysis to evaluate the accuracy of RADTs for diagnosis of RSV infection and to determine factors associated with accuracy estimates. We searched EMBASE and PubMed for diagnostic-accuracy studies of commercialized RSV RADTs. Studies reporting sensitivity and specificity data compared to a reference standard (reverse transcriptase PCR [RT-PCR], immunofluorescence, or viral culture) were considered. Two reviewers independently extracted data on study characteristics, diagnostic-accuracy estimates, and study quality. Accuracy estimates were pooled using bivariate random-effects regression models. Heterogeneity was investigated with prespecified subgroup analyses. Seventy-one articles met inclusion criteria. Overall, RSV RADT pooled sensitivity and specificity were 80% (95% confidence interval [CI], 76% to 83%) and 97% (95% CI, 96% to 98%), respectively. Positive- and negative-likelihood ratios were 25.5 (95% CI, 18.3 to 35.5) and 0.21 (95% CI, 0.18 to 0.24), respectively. Sensitivity was higher in children (81% [95% CI, 78%, 84%]) than in adults (29% [95% CI, 11% to 48%]). Because of this disparity, further subgroup analyses were restricted to pediatric data (63 studies). Test sensitivity was poorest using RT-PCR as a reference standard and highest using immunofluorescence (74% versus 88%; P < 0.001). Industry-sponsored studies reported significantly higher sensitivity (87% versus 78%; P = 0.01). Our results suggest that the poor sensitivity of RSV RADTs in adults may preclude their use in this population. Furthermore, industry-sponsored studies and those that did not use RT-PCR as a reference standard likely overestimated test sensitivity. PMID- 26354817 TI - Comparing Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry and Phenotypic and Molecular Methods for Identification of Species within the Streptococcus anginosus Group. AB - The heterogeneity of members of the Streptococcus anginosus group (SAG) has traditionally hampered their correct identification. Recently, the group was subdivided into 6 taxa whose prevalence among human infections is poorly described. We evaluated the accuracy of the Rapid ID32 Strep test, matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), and a PCR multiplex method to identify 212 SAG isolates recovered from human infections to the species and subspecies level by using multilocus sequence analysis (MLSA) as the gold standard. We also determined the antimicrobial susceptibilities of the isolates. Representatives of all SAG taxa were found among our collection. MALDI-TOF MS and the Rapid ID32 Strep test correctly identified 92% and 68% of the isolates to the species level, respectively, but showed poor performance at the subspecies level, and the latter was responsible for major identification errors. The multiplex PCR method results were in complete agreement with the MLSA identifications but failed to distinguish the subspecies Streptococcus constellatus subsp. pharyngis and S. constellatus subsp. viborgensis. A total of 145 MLSA sequence types were present in our collection, indicating that within each taxon a number of different lineages are capable of causing infection. Significant antibiotic resistance was observed only to tetracycline, erythromycin, and clindamycin and was present in most taxa. MALDI TOF MS is a reliable method for routine SAG species identification, while the need for identification to the subspecies level is not clearly established. PMID- 26354818 TI - Significance of a Positive Toxoplasma Immunoglobulin M Test Result in the United States. AB - A positive Toxoplasma immunoglobulin M (IgM) result is often interpreted as a marker of an acute infection. However, IgM can persist for several years, and Toxoplasma commercial IgM diagnostic test kits can yield a number of false positive results. For these reasons, a chronic Toxoplasma infection can be erroneously classified as an acute infection, resulting in serious adverse consequences, especially in pregnant women, leading to emotional distress and unnecessary interventions, including termination of pregnancy. Interpretation of Toxoplasma serology at a reference laboratory can help differentiate a recently acquired infection from a chronic infection. Serological test results for 451 patients with positive Toxoplasma IgM and IgG test results obtained at nonreference laboratories (NRLs) that were referred to Palo Alto Medical Foundation Toxoplasma Serology Laboratory (PAMF-TSL) to determine whether the patient was acutely or chronically infected were retrospectively reviewed. PAMF TSL results established that of the 451 patients, 335 (74%) had a chronic infection, 100 (22%) had an acute infection, and 7 (2%) were not infected, and for 9 (2%), results were indeterminate. Positive Toxoplasma IgM and IgG test results obtained at NRLs cannot accurately distinguish between acute and chronic infections. To do so, testing at reference laboratories is required, as mandated in 1997 in a letter from the Food and Drug Administration (FDA) to clinicians and laboratories in the United States. PMID- 26354819 TI - Optimal Cutoff Titers for Indirect Immunofluorescence Assay for Diagnosis of Scrub Typhus. AB - We determined the optimal cutoff titers in admission and convalescent-phase samples for scrub typhus indirect immunofluorescence assay using Bayesian latent class models. Cutoff titers of >=1:3,200 in an admission sample or of a >=4-fold rise to >=1:3,200 in a convalescent-phase sample provided the highest accuracy (sensitivity, 81.6%; specificity, 100%). PMID- 26354820 TI - Improved syntheses of beta-octabromo-meso-triarylcorrole derivatives. AB - In spite of significant applications as starting materials for a variety of metallocorrole derivatives, free-base beta-octabromo-meso-triarylcorroles continue to be viewed as inaccessible. The reasons range from the need for tedious column-chromatographic purification to limitations of the reductive demetallation protocol for selected systems. Here we report that column chromatography may be entirely avoided for a number of beta-octabromo-meso-tris(p X-phenyl)corrole derivatives, where X=CF3, NO2, F, H, CH3, and OCH3; instead, analytically pure products may be obtained by recrystallization from chloroform/methanol. In addition, we have presented an optimized synthesis of the heretofore inaccessible, sterically hindered ligand beta-octabromo-meso-tris(2,6 dichlorophenyl)corrole, H3[Br8TDCPC], via reductive demetallation of the corresponding Mn(III) complex. With our earlier report of beta-octabromo-meso tris(pentafluorophenyl)corrole, H3[Br8TPFPC], a comprehensive set of optimized synthetic protocols are thus in place for a good number of beta-octabromo-meso triarylcorrole ligands. Furthermore, we have illustrated the use of these ligands by synthesizing the iron complexes Fe[Br8TDCPC]Cl and Fe[Br8TDCPC](py)2, of which the latter lent itself to single-crystal X-ray structure determination. PMID- 26354821 TI - Left atrial appendage closure: First in man with the 4th generation WATCHMAN device. AB - OBJECTIVES: To evaluate the feasibility and safety of the fourth generation WATCHMAN device. BACKGROUND: The WATCHMAN left atrial appendage (LAA) closure device has been shown to be non-inferior to conventional oral anticoagulation with warfarin for stroke prevention in patients with non-valvular atrial fibrillation. A new (fourth) generation of the WATCHMAN device was designed to facilitate easier delivery and improve safety. METHODS: We conducted a prospective, non-randomized study of LAA closure with use of the 4(th) generation WATCHMAN device in 36 patients with non-valvular atrial fibrillation. Follow-up was performed at 45 days, 6 months and 12 months following implantation. RESULTS: The mean age of the population was 73 +/- 6 years and 67% were male. The mean CHADS2 and CHA2 DS2-VASc Score were 2.5 and 4.5, respectively. The device was implanted successfully in 34/36 (94%). No serious hospital complications related to the device or procedure occurred. During 12 month follow-up, three ischemic strokes (8%), one hemorrhagic stroke (3%), one TIA (3%) and three deaths (9%) occurred. Device-associated thrombus formation was detected in one patient (3%) during six-month follow-up and was treated successfully with low molecular weight heparin. CONCLUSIONS: LAA closure with the 4(th) generation WATCHMAN device is feasible and safe. New technical features may contribute to a better performance of the occluder, particularly regarding the risk of pericardial effusions. PMID- 26354824 TI - Erratum for Fan et al., Cerebral Toxocariasis: Silent Progression to Neurodegenerative Disorders? PMID- 26354822 TI - Visceral Leishmaniasis in China: an Endemic Disease under Control. AB - Visceral leishmaniasis (VL) caused by Leishmania spp. is an important vector borne and largely zoonotic disease. In China, three epidemiological types of VL have been described: anthroponotic VL (AVL), mountain-type zoonotic VL (MT-ZVL), and desert-type ZVL (DT-ZVL). These are transmitted by four different sand fly species: Phlebotomus chinensis, P. longiductus, P. wui, and P. alexandri. In 1951, a detailed survey of VL showed that it was rampant in the vast rural areas west, northwest, and north of the Yangtze River. Control programs were designed and implemented stringently by the government at all administrative levels, resulting in elimination of the disease from most areas of endemicity, except the western and northwestern regions. The control programs consisted of (i) diagnosis and chemotherapy of patients, (ii) identification, isolation, and disposal of infected dogs, and (iii) residual insecticide indoor spraying for vector control. The success of the control programs is attributable to massive and effective mobilization of the general public and health workers to the cause. Nationally, the annual incidence is now very low, i.e., only 0.03/100,000 according to the available 2011 official record. The overwhelming majority of cases are reported from sites of endemicity in the western and northwestern regions. Here, we describe in some depth and breadth the current status of epidemiology, diagnosis, treatment, and prevention of the disease, with particular reference to the control programs. Pertinent information has been assembled from scattered literature of the past decades in different languages that are not readily accessible to the scientific community. The information provided constitutes an integral part of our knowledge on leishmaniasis in the global context and will be of special value to those interested in control programs. PMID- 26354825 TI - Correction for Diaz, Paragonimiasis Acquired in the United States: Native and Nonnative Species. AB - Volume 26, no. 3, p. 493-504, 2013. Page 497: The snail shown in Fig. 8 is not a slender walker snail (Pomatiopsis lapidaria), as indicated in the legend of the figure, but rather a sharp hornsnail (Pleurocera acuta). The correct image (that of the slender walker snail, Pomatiopsis lapidaria; courtesy of Steve Cringan, photographer) is shown below. PMID- 26354826 TI - A comparison of hyperelastic constitutive models applicable to brain and fat tissues. AB - In some soft biological structures such as brain and fat tissues, strong experimental evidence suggests that the shear modulus increases significantly under increasing compressive strain, but not under tensile strain, whereas the apparent Young's elastic modulus increases or remains almost constant when compressive strain increases. These tissues also exhibit a predominantly isotropic, incompressible behaviour. Our aim is to capture these seemingly contradictory mechanical behaviours, both qualitatively and quantitatively, within the framework of finite elasticity, by modelling a soft tissue as a homogeneous, isotropic, incompressible, hyperelastic material and comparing our results with available experimental data. Our analysis reveals that the Fung and Gent models, which are typically used to model soft tissues, are inadequate for the modelling of brain or fat under combined stretch and shear, and so are the classical neo-Hookean and Mooney-Rivlin models used for elastomers. However, a subclass of Ogden hyperelastic models are found to be in excellent agreement with the experiments. Our findings provide explicit models suitable for integration in large-scale finite-element computations. PMID- 26354823 TI - Laboratory Diagnosis of Pertussis. AB - The introduction of vaccination in the 1950s significantly reduced the morbidity and mortality of pertussis. However, since the 1990s, a resurgence of pertussis has been observed in vaccinated populations, and a number of causes have been proposed for this phenomenon, including improved diagnostics, increased awareness, waning immunity, and pathogen adaptation. The resurgence of pertussis highlights the importance of standardized, sensitive, and specific laboratory diagnoses, the lack of which is responsible for the large differences in pertussis notifications between countries. Accurate laboratory diagnosis is also important for distinguishing between the several etiologic agents of pertussis like diseases, which involve both viruses and bacteria. If pertussis is diagnosed in a timely manner, antibiotic treatment of the patient can mitigate the symptoms and prevent transmission. During an outbreak, timely diagnosis of pertussis allows prophylactic treatment of infants too young to be (fully) vaccinated, for whom pertussis is a severe, sometimes fatal disease. Finally, reliable diagnosis of pertussis is required to reveal trends in the (age-specific) disease incidence, which may point to changes in vaccine efficacy, waning immunity, and the emergence of vaccine-adapted strains. Here we review current approaches to the diagnosis of pertussis and discuss their limitations and strengths. In particular, we emphasize that the optimal diagnostic procedure depends on the stage of the disease, the age of the patient, and the vaccination status of the patient. PMID- 26354827 TI - Dynamic footprint of sequestration in the molecular fluctuations of osteopontin. AB - The sequestration of calcium phosphate by unfolded proteins is fundamental to the stabilization of biofluids supersaturated with respect to hydroxyapatite, such as milk, blood or urine. The unfolded state of osteopontin (OPN) is thought to be a prerequisite for this activity, which leads to the formation of core-shell calcium phosphate nanoclusters. We report on the structures and dynamics of a native OPN peptide from bovine milk, studied by neutron spectroscopy and small angle X-ray and neutron scattering. The effects of sequestration are quantified on the nanosecond- angstrom resolution by elastic incoherent neutron scattering. The molecular fluctuations of the free phosphopeptide are in agreement with a highly flexible protein. An increased resilience to diffusive motions of OPN is corroborated by molecular fluctuations similar to those observed for globular proteins, yet retaining conformational flexibilities. The results bring insight into the modulation of the activity of OPN and phosphopeptides with a role in the control of biomineralization. The quantification of such effects provides an important handle for the future design of new peptides based on the dynamics activity relationship. PMID- 26354828 TI - Fast nastic motion of plants and bioinspired structures. AB - The capability to sense and respond to external mechanical stimuli at various timescales is essential to many physiological aspects in plants, including self protection, intake of nutrients and reproduction. Remarkably, some plants have evolved the ability to react to mechanical stimuli within a few seconds despite a lack of muscles and nerves. The fast movements of plants in response to mechanical stimuli have long captured the curiosity of scientists and engineers, but the mechanisms behind these rapid thigmonastic movements are still not understood completely. In this article, we provide an overview of such thigmonastic movements in several representative plants, including Dionaea, Utricularia, Aldrovanda, Drosera and Mimosa. In addition, we review a series of studies that present biomimetic structures inspired by fast-moving plants. We hope that this article will shed light on the current status of research on the fast movements of plants and bioinspired structures and also promote interdisciplinary studies on both the fundamental mechanisms of plants' fast movements and biomimetic structures for engineering applications, such as artificial muscles, multi-stable structures and bioinspired robots. PMID- 26354829 TI - Aerobically respiring prokaryotic strains exhibit a broader temperature-pH salinity space for cell division than anaerobically respiring and fermentative strains. AB - Biological processes on the Earth operate within a parameter space that is constrained by physical and chemical extremes. Aerobic respiration can result in adenosine triphosphate yields up to over an order of magnitude higher than those attained anaerobically and, under certain conditions, may enable microbial multiplication over a broader range of extremes than other modes of catabolism. We employed growth data published for 241 prokaryotic strains to compare temperature, pH and salinity values for cell division between aerobically and anaerobically metabolizing taxa. Isolates employing oxygen as the terminal electron acceptor exhibited a considerably more extensive three-dimensional phase space for cell division (90% of the total volume) than taxa using other inorganic substrates or organic compounds as the electron acceptor (15% and 28% of the total volume, respectively), with all groups differing in their growth characteristics. Understanding the mechanistic basis of these differences will require integration of research into microbial ecology, physiology and energetics, with a focus on global-scale processes. Critical knowledge gaps include the combined impacts of diverse stress parameters on Gibbs energy yields and rates of microbial activity, interactions between cellular energetics and adaptations to extremes, and relating laboratory-based data to in situ limits for cell division. PMID- 26354830 TI - Unreliable numbers: error and harm induced by bad design can be reduced by better design. AB - Number entry is a ubiquitous activity and is often performed in safety- and mission-critical procedures, such as healthcare, science, finance, aviation and in many other areas. We show that Monte Carlo methods can quickly and easily compare the reliability of different number entry systems. A surprising finding is that many common, widely used systems are defective, and induce unnecessary human error. We show that Monte Carlo methods enable designers to explore the implications of normal and unexpected operator behaviour, and to design systems to be more resilient to use error. We demonstrate novel designs with improved resilience, implying that the common problems identified and the errors they induce are avoidable. PMID- 26354831 TI - Circulating microparticles and the risk of thrombosis in inherited deficiencies of antithrombin, protein C and protein S. AB - Many subjects carrying inherited thrombophilic defects will never experience venous thromboembolism (VTE) while other individuals developed recurrent VTE with no known additional risk factors. High levels of circulating microparticles (MP) have been associated with increased risk of VTE in patients with factor V Leiden and prothrombin G20210A mutation, suggesting a possible contribution of MP in the hypercoagulability of mild genetic thrombophilia. The role of MP as additional risk factor of VTE in carriers of natural clotting inhibitors defects (severe thrombophilia) has never been assessed. Plasma levels of annexin V-MP, endothelial-derived MP (EMP), platelet-derived MP (PMP), tissue factor-bearing MP (TF+) and the MP procoagulant activity (PPL) were measured in 132 carriers of natural anticoagulant deficiencies (25 antithrombin, 63 protein C and 64 protein S defect) and in 132 age and gender-matched healthy controls. Carriers of natural anticoagulant deficiencies, overall and separately considered, presented with higher median levels of annexin V-MP, EMP, PMP, TF+MP and PPL activity than healthy controls (p< 0.001, < 0.001, < 0.01, 0.025 and 0.03, respectively). Symptomatic carriers with a previous episode of VTE had significantly higher median levels of annexin-V MP than those without VTE (p=0.027). Carriers with high levels of annexin V-MP, EMP and PMP had an adjusted OR for VTE of 3.36 (95% CI, 1.59 to 7.11), 9.26 (95% CI, 3.55 to 24.1) and 2.72 (95%CI, 1.16 to 6.38), respectively. Elevated levels of circulating MP can play a role in carriers of mild and severe inherited thrombophilia. The clinical implications of this association remain to be defined. PMID- 26354832 TI - Covalency-reinforced oxygen evolution reaction catalyst. AB - The oxygen evolution reaction that occurs during water oxidation is of considerable importance as an essential energy conversion reaction for rechargeable metal-air batteries and direct solar water splitting. Cost-efficient ABO3 perovskites have been studied extensively because of their high activity for the oxygen evolution reaction; however, they lack stability, and an effective solution to this problem has not yet been demonstrated. Here we report that the Fe(4+)-based quadruple perovskite CaCu3Fe4O12 has high activity, which is comparable to or exceeding those of state-of-the-art catalysts such as Ba(0.5)Sr(0.5)Co(0.8)Fe(0.2)O(3-delta) and the gold standard RuO2. The covalent bonding network incorporating multiple Cu(2+) and Fe(4+) transition metal ions significantly enhances the structural stability of CaCu3Fe4O12, which is key to achieving highly active long-life catalysts. PMID- 26354833 TI - Fractal and twin SVM-based handgrip recognition for healthy subjects and trans radial amputees using myoelectric signal. AB - Identifying functional handgrip patterns using surface electromygram (sEMG) signal recorded from amputee residual muscle is required for controlling the myoelectric prosthetic hand. In this study, we have computed the signal fractal dimension (FD) and maximum fractal length (MFL) during different grip patterns performed by healthy and transradial amputee subjects. The FD and MFL of the sEMG, referred to as the fractal features, were classified using twin support vector machines (TSVM) to recognize the handgrips. TSVM requires fewer support vectors, is suitable for data sets with unbalanced distributions, and can simultaneously be trained for improving both sensitivity and specificity. When compared with other methods, this technique resulted in improved grip recognition accuracy, sensitivity, and specificity, and this improvement was significant (kappa=0.91). PMID- 26354834 TI - Cranial nerve palsies after shunting of an isolated fourth ventricle. AB - An isolated fourth ventricle is characterised by cerebrospinal fluid (CSF) trapping in the fourth ventricle. Although there is no consensus regarding treatment, ventriculoperitoneal (VP) shunting of the fourth ventricle is an option. Complications include infection, mechanical irritation of the brainstem, malfunction and overdrainage. Cranial nerve palsy is a rare complication and has been mostly described in children. We present two adult cases of abducens and facial nerve palsies occurring secondary to this procedure. Placement of a higher resistance valve brought about complete recovery in one patient while withdrawal of the catheter by a few millimetres led to complete recovery in the second patient. PMID- 26354835 TI - Splenic injury as a complication of colonoscopy: more common than we think? AB - Splenic injury during colonoscopy is thought to be rare. The case reported here would not have been diagnosed if the patient had not presented with a pleural effusion. It is likely that this complication may present with differing severities of clinical features with a significant proportion being thought to be due to expected postcolonoscopy insufflation discomfort. This complication is under-recognised and under-reported and therefore is unlikely to be thought of as a diagnosis. A 63-year-old woman had an elective day case colonoscopy but did not seek medical attention for the abdominal pain following the procedure. She presented to hospital 6 weeks after the procedure with dyspnoea and hypoxia. She was diagnosed with a parapneumonic pleural effusion but the CT scan also discovered a splenic haematoma for which there was no other cause in her history other than the colonoscopy 6 weeks prior. PMID- 26354836 TI - IgA vasculitis (formerly Henoch-Schonlein purpura) in an adult with systemic lupus erythematosus. AB - We report a case of a 65-year-old man with systemic lupus erythematosus (SLE) and antiphospholipid syndrome, presenting palpable purpuric lesions, necrotic blisters and swelling ankles, after a previous tracheobronchitis episode. Laboratory data were remarkable for mild proteinuria and imaging studies were normal. A skin biopsy showed IgA deposits on superficial dermal capillaries and IgA vasculitis (IgAV) (former Henoch-Schonlein purpura) was assumed. The patient was treated with colchicine, deflazacort and azathioprine, but as a regression in the purpuric lesions was noted, a decline in renal function was detected. A kidney biopsy revealed mesangial proliferation with IgA deposition and IgAV nephritis was considered. Immunosuppressive treatment was adjusted, with progressive normalisation of renal function and disappearance of proteinuria over a monthly follow-up; after 6 months, total remission was achieved. To the best of our knowledge, this is the first reported case of IgAV in an adult patient with SLE. PMID- 26354837 TI - Bradycardia in anorexia nervosa. AB - We present a case of a 24-year-old woman initially referred for a permanent pacemaker for symptomatic sinus bradycardia. Further consultations revealed significant weight loss and subsequent psychiatric review confirmed a diagnosis of anorexia nervosa. PMID- 26354838 TI - Cardiac metastasis of oral squamous cell carcinoma. AB - We present a case of isolated cardiac metastasis of oral squamous cell carcinoma. An 89-year-old woman was due to undergo curative resection of a histologically proven squamous cell carcinoma of the retromolar region. On admission, it was noted that there were ECG changes, and following further investigations, the patient was diagnosed with a cardiac metastasis of her oral malignancy. The presentation, including the diagnostic difficulties, as well as the clinical features of this rare case, are discussed. PMID- 26354839 TI - Recurrent respiratory infections and unusual radiology: a woman with Kartagener's syndrome. AB - A 39-year-old woman with known situs inversus and a medical history of asthma had been suffering from recurring bronchial pneumonias and sinusitis for as long as she could remember. After being treated several times with antibiotics due to the frequent respiratory infections and after a CT scan that showed bilateral bronchiectasis, she was referred to the department of respiratory diseases, where another confirming X-ray and a bronchoscopy were performed based on a suspicion of Kartagener's syndrome. PMID- 26354840 TI - Cervical diverticulitis: a novel complication of a neonatal colonic interposition graft following oesophagectomy. AB - A 47-year-old woman presented to a tertiary emergency department with an 8-day history of odynophagia, a 4 cm swelling on her left neck and intermittent fevers. Shortly following her birth, a congenital oesophageal atresia had been managed surgically with colonic interposition graft. Contrast CT of the neck demonstrated several large diverticula within her interposition graft at the level of the cervical vertebrae. A colocutaneous fistula was identified between the colon and left neck, with an associated abscess. The patient received intravenous meropenem followed by abscess drainage. A high output fistula developed at the drainage site, and the patient required intravenous fluids and stoma placement to manage fluid discharge. She left the hospital after a 17-day stay. At 6-month follow-up, the wound was erythematous, but the patient was otherwise well. We believe that this is the first reported case of diverticular disease arising in what was originally neonatal colon interposed for oesophageal atresia at birth. PMID- 26354841 TI - Focal segmental glomerulosclerosis in a patient with mantle cell lymphoma. AB - Mantle cell lymphoma (MCL) is a rare lymphoid neoplasm occurring in about 6% of all non-Hodgkin's lymphomas. Although nephrotic syndrome due to various glomerulopathies is well described in patients with lymphomas, focal segmental glomerulosclerosis (FSGS) with MCL has been reported only once before. We present a second case of FSGS associated with MCL that was resistant to standard treatment of FSGS but resolved when the underlying MCL was treated. PMID- 26354842 TI - Increased systolic load causes adverse remodeling of fetal aortic and mitral valves. AB - While abnormal hemodynamic forces alter fetal myocardial growth, little is known about whether such insults affect fetal cardiac valve development. We hypothesized that chronically elevated systolic load would detrimentally alter fetal valve growth. Chronically instrumented fetal sheep received either a continuous infusion of adult sheep plasma to increase fetal blood pressure, or a lactated Ringer's infusion as a volume control beginning on day 126 +/- 4 of gestation. After 8 days, mean arterial pressure was higher in the plasma infusion group (63.0 mmHg vs. 41.8 mmHg, P < 0.05). Mitral annular septal-lateral diameter (11.9 mm vs. 9.1 mm, P < 0.05), anterior leaflet length (7.7 mm vs. 6.4 mm, P < 0.05), and posterior leaflet length (P2; 4.0 mm vs. 3.0 mm, P < 0.05) were greater in the elevated load group. mRNA levels of Notch-1, TGF-beta2, Wnt-2b, BMP-1, and versican were suppressed in aortic and mitral valve leaflets; elastin and alpha1 type I collagen mRNA levels were suppressed in the aortic valves only. We conclude that sustained elevated arterial pressure load on the fetal heart valve leads to anatomic remodeling and, surprisingly, suppression of signaling and extracellular matrix genes that are important to valve development. These novel findings have important implications on the developmental origins of valve disease and may have long-term consequences on valve function and durability. PMID- 26354843 TI - Variable responses of regional renal oxygenation and perfusion to vasoactive agents in awake sheep. AB - Vasoactive agents are used in critical care to optimize circulatory function, but their effects on renal tissue oxygenation in the absence of anesthesia remain largely unknown. Therefore, we assessed the effects of multiple vasoactive agents on regional kidney oxygenation in awake sheep. Sheep were surgically instrumented with pulmonary and renal artery flow probes, and combination fiber-optic probes, in the renal cortex and medulla, comprising a fluorescence optode to measure tissue Po2 and a laser-Doppler probe to assess tissue perfusion. Carotid arterial and renal venous cannulas enabled measurement of arterial pressure and total renal oxygen delivery and consumption. Norepinephrine (0.1 or 0.8 MUg.kg(-1).min( 1)) dose-dependently reduced cortical and medullary laser Doppler flux (LDF) and Po2 without significantly altering renal blood flow (RBF), or renal oxygen delivery or consumption. Angiotensin II (9.8 +/- 2.1 MUg/h) reduced RBF by 21%, renal oxygen delivery by 28%, oxygen consumption by 18%, and medullary Po2 by 38%, but did not significantly alter cortical Po2 or cortical or medullary LDF. Arginine vasopressin (3.3 +/- 0.5 MUg/h) caused similar decreases in RBF and renal oxygen delivery, but did not significantly alter renal oxygen consumption or cortical or medullary LDF or Po2. Captopril had no observable effects on cortical or medullary LDF or Po2, at a dose that increased renal oxygen delivery by 24%, but did not significantly alter renal oxygen consumption. We conclude that vasoactive agents have diverse effects on regional kidney oxygenation in awake sheep that are not predictable from their effects on LDF, RBF, or total renal oxygen delivery and consumption. PMID- 26354844 TI - Plasticity in breathing and arterial blood pressure following acute intermittent hypercapnic hypoxia in infant rat pups with a partial loss of 5-HT neurons. AB - The role of serotonin (5-HT) neurons in cardiovascular responses to acute intermittent hypoxia (AIH) has not been studied in the neonatal period. We hypothesized that a partial loss of 5-HT neurons would reduce arterial blood pressure (BP) at rest, increase the fall in BP during hypoxia, and reduce the long-term facilitation of breathing (vLTF) and BP following AIH. We exposed 2-wk old, 5,7-dihydroxytryptamine-treated and controls to AIH (10% O2; n = 13 control, 14 treated), acute intermittent hypercapnia (5% CO2; n = 12 and 11), or acute intermittent hypercapnic hypoxia (AIHH; 10% O2, 5% CO2; n = 15 and 17). We gave five 5-min challenges of AIH and acute intermittent hypercapnia, and twenty ~20-s challenges of AIHH to mimic sleep apnea. Systolic BP (sBP), diastolic BP, mean arterial pressure, heart rate (HR), ventilation (Ve), and metabolic rate (Vo2) were continuously monitored. 5,7-Dihydroxytryptamine induced an ~35% loss of 5-HT neurons from the medullary raphe. Compared with controls, pups deficient in 5-HT neurons had reduced resting sBP (~6 mmHg), mean arterial pressure (~5 mmHg), and HR (56 beats/min), and experienced a reduced drop in BP during hypoxia. AIHH induced vLTF in both groups, reflected in increased Ve and Ve/Vo2, and decreased arterial Pco2. The sBP of pups deficient in 5-HT neurons, but not controls, was increased 1 h following AIHH. Our data suggest that a relatively small loss of 5 HT neurons compromises resting BP and HR, but has no influence on ventilatory plasticity induced by AIHH. AIHH may be useful for reversing cardiorespiratory defects related to partial 5-HT system dysfunction. PMID- 26354845 TI - Nonlinear identification of the total baroreflex arc. AB - The total baroreflex arc [the open-loop system relating carotid sinus pressure (CSP) to arterial pressure (AP)] is known to exhibit nonlinear behaviors. However, few studies have quantitatively characterized its nonlinear dynamics. The aim of this study was to develop a nonlinear model of the sympathetically mediated total arc without assuming any model form. Normal rats were studied under anesthesia. The vagal and aortic depressor nerves were sectioned, the carotid sinus regions were isolated and attached to a servo-controlled piston pump, and the AP and sympathetic nerve activity (SNA) were measured. CSP was perturbed using a Gaussian white noise signal. A second-order Volterra model was developed by applying nonparametric identification to the measurements. The second-order kernel was mainly diagonal, but the diagonal differed in shape from the first-order kernel. Hence, a reduced second-order model was similarly developed comprising a linear dynamic system in parallel with a squaring system in cascade with a slower linear dynamic system. This "Uryson" model predicted AP changes 12% better (P < 0.01) than a linear model in response to new Gaussian white noise CSP. The model also predicted nonlinear behaviors, including thresholding and mean responses to CSP changes about the mean. Models of the neural arc (the system relating CSP to SNA) and peripheral arc (the system relating SNA to AP) were likewise developed and tested. However, these models of subsystems of the total arc showed approximately linear behaviors. In conclusion, the validated nonlinear model of the total arc revealed that the system takes on an Uryson structure. PMID- 26354846 TI - Melatonin receptor signaling contributes to neuroprotection upon arousal from torpor in thirteen-lined ground squirrels. AB - The brain of mammalian hibernators is naturally protected. Hibernating ground squirrels undergo rapid and extreme changes in body temperature and brain perfusion as they cycle between lengthy torpor bouts and brief periods of euthermia called interbout arousals (IBAs). Arousal from torpor to IBA occurs rapidly, but there is no evidence of brain injury accompanying this extreme physiological transition. Production of the hormone melatonin accompanies arousal, suggesting that it plays a protective role at this time. Here, we investigated mechanisms of melatonin receptor-mediated protection in the brain of the hibernating ground squirrel. We administered the competitive melatonin receptor antagonist luzindole (30 mg/kg ip) to ground squirrels at the predicted end of a torpor bout, triggering an arousal. We found that luzindole-treated animals exhibited caspase-3 activity two times higher than vehicle-treated animals in the hypothalamus at midarousal (P = 0.01), suggesting that melatonin receptor signaling is important for protection in this brain region. We also found a 30% decline in succinate-fueled mitochondrial respiration in luzindole treated animals compared with vehicle-treated animals (P = 0.019), suggesting that melatonin receptor signaling is important for optimal mitochondrial function during arousal from torpor. The mitochondrial effects of luzindole treatment were seen only during the hibernation season, indicating that this effect is specifically important for arousal from torpor. These data provide evidence for the protective role of melatonin receptor signaling during the extreme physiological transition that occurs when a hibernating mammal arouses from torpor and provide further evidence for regional and seasonal changes in the hibernator brain. PMID- 26354847 TI - Differences in control of parasympathetic vasodilation between submandibular and sublingual glands in the rat. AB - We examined blood flow in the submandibular gland (SMGBF) and sublingual gland (SLGBF) during electrical stimulation of the central cut end of the lingual nerve (LN) in the urethane-anesthetized rats using a laser speckle imaging flow meter. LN stimulation elicited intensity- and frequency-dependent SMGBF and SLGBF increases, and the magnitude of the SMGBF increase was higher than that of the SLGBF increase. The increase in both glands was significantly inhibited by intravenous administration of the autonomic cholinergic ganglion blocker hexamethonium. The antimuscarinic agent atropine markedly inhibited the SMGBF increase and partly inhibited the SLGBF increase. The atropine-resistant SLGBF increase was significantly inhibited by infusion of vasoactive intestinal peptide (VIP) receptor antagonist, although administration of VIP receptor antagonist alone had no effect. The recovery time to the basal blood flow level was shorter after LN stimulation than after administration of VIP. However, the recovery time after LN stimulation was significantly delayed by administration of atropine in a dose-dependent manner to the same level as after administration of VIP. Our results indicate that 1) LN stimulation elicits both a parasympathetic SMGBF increase mainly evoked by cholinergic fibers and a parasympathetic SLGBF increase evoked by cholinergic and noncholinergic fibers, and 2) VIP-ergic mechanisms are involved in the noncholinergic SLGBF increase and are activated when muscarinic mechanisms are deactivated. PMID- 26354848 TI - Salt-induced sympathoexcitation involves vasopressin V1a receptor activation in the paraventricular nucleus of the hypothalamus. AB - A high-salt diet can lead to hydromineral imbalance and increases in plasma sodium and osmolality. It is recognized as one of the major contributing factors for cardiovascular diseases such as hypertension. The paraventricular nucleus (PVN) plays a pivotal role in osmotically driven sympathoexcitation and high blood pressure, the precise mechanisms of which are not fully understood. Recent evidence indicates that AVP released from magnocellular neurons might be involved in this process. Using a combination of in vivo and in situ studies, we sought to investigate whether AVP, acting on PVN neurons, can change mean arterial pressure (MAP) and sympathetic nerve activity (SNA) in euhydrated male rats. Furthermore, we wanted to determine whether V1a receptors on PVN neurons would be involved in salt-induced sympathoexcitation and hypertension. In rats, 4 days of salt loading (NaCl 2%) elicited a significant increase in plasma osmolality (39 +/- 7 mosmol/kgH2O), an increase in MAP (26 +/- 2 mmHg, P < 0.001), and sympathoexcitation compared with euhydrated rats. Microinjection of AVP into the PVN of conscious euhydrated animals (100 nl, 3 MUM) elicited a pressor response (14 +/- 2 mmHg) and a significant increase in lumbar SNA (100 nl, 1 mM) (19 +/- 5%). Pretreatment with a V1a receptor antagonist, microinjected bilaterally into the PVN of salt-loaded animals, elicited a decrease in lumbar SNA (-14 +/- 5%) and MAP (-19 +/- 5 mmHg), when compared with the euhydrated group. Our findings show that AVP plays an important role in modulating the salt-induced sympathoexcitation and high blood pressure, via V1a receptors, within the PVN of male rats. As such, V1a receptors in the PVN might contribute to neurogenic hypertension in individuals consuming a high-salt diet. PMID- 26354849 TI - Oxygenation properties and isoform diversity of snake hemoglobins. AB - Available data suggest that snake hemoglobins (Hbs) are characterized by a combination of unusual structural and functional properties relative to the Hbs of other amniote vertebrates, including oxygenation-linked tetramer-dimer dissociation. However, standardized comparative data are lacking for snake Hbs, and the Hb isoform composition of snake red blood cells has not been systematically characterized. Here we present the results of an integrated analysis of snake Hbs and the underlying alpha- and beta-type globin genes to characterize 1) Hb isoform composition of definitive erythrocytes, and 2) the oxygenation properties of isolated isoforms as well as composite hemolysates. We used species from three families as subjects for experimental studies of Hb function: South American rattlesnake, Crotalus durissus (Viperidae); Indian python, Python molurus (Pythonidae); and yellow-bellied sea snake, Pelamis platura (Elapidae). We analyzed allosteric properties of snake Hbs in terms of the Monod-Wyman-Changeux model and Adair four-step thermodynamic model. Hbs from each of the three species exhibited high intrinsic O2 affinities, low cooperativities, small Bohr factors in the absence of phosphates, and high sensitivities to ATP. Oxygenation properties of the snake Hbs could be explained entirely by allosteric transitions in the quaternary structure of intact tetramers, suggesting that ligation-dependent dissociation of Hb tetramers into alphabeta-dimers is not a universal feature of snake Hbs. Surprisingly, the major Hb isoform of the South American rattlesnake is homologous to the minor HbD of other amniotes and, contrary to the pattern of Hb isoform differentiation in birds and turtles, exhibits a lower O2 affinity than the HbA isoform. PMID- 26354851 TI - The impact of orofacial dysfunction in cerebral palsy. PMID- 26354850 TI - GSTP1 and GSTO1 single nucleotide polymorphisms and the response of bladder cancer patients to intravesical chemotherapy. AB - SNPs may restrict cell detoxification activity and be a potential risk factor for cancer chemosensitivity. We evaluated the predictive value of these polymorphisms on the sensitivity of bladder cancer patients to epirubicin and mitomycin chemotherapy instillation as well as their toxicities. SNPs were analyzed by TaqMan genotyping assays in 130 patients treated with epirubicin and 114 patients treated with mitomycin. Recurrence-free survival (RFS) was estimated by the Kaplan-Meier method, and hazard ratios (HRs) and 95% confidence intervals (CIs) of the HRs were derived from multivariate Cox proportional hazard models. GSTP1 rs1695 and GSTO1 rs4925 were also associated with RFS in the epirubicin group. Patients carrying the GSTP1 AG+GG and GSTO1 AC+AA genotypes had an unfavorable RFS. Patients with the GSTP1 AA and GSTO1 CC genotypes had a reduced risk of recurrence after the instillation of epirubicin. In addition, patients with the GSTP1 rs1695 AA genotype had an increased risk of irritative voiding symptoms; while patients with the GSTO1 rs4925 CC genotype had a decreased risk of hematuria. Our results suggest that GSTP1 and GSTO1 polymorphisms are associated with epirubicin treatment outcomes as well as with epirubicin-related toxicity. PMID- 26354852 TI - STIP overexpression confers oncogenic potential to human non-small cell lung cancer cells by regulating cell cycle and apoptosis. AB - Sip1/tuftelin-interacting protein (STIP), a multidomain nuclear protein, is a novel factor associated with the spliceosome, yet its role and molecular function in cancer remain unknown. In this study, we show, for the first time, that STIP is overexpressed in non-small cell lung cancer (NSCLC) tissues compared to adjacent normal lung tissues. The depletion of endogenous STIP inhibited NSCLC cell proliferation in vitro and in vivo, caused cell cycle arrest and induced apoptosis. Cell cycle arrest at the G2/M phase was associated with the expression and activity of the cyclin B1-CDK1 (cyclin-dependent kinase 1) complex. We also provide evidence that STIP knockdown induced apoptosis by activating both caspase 9 and caspase-3 and by altering the Bcl-2/Bax expression ratio. RNA sequencing data indicated that the MAPK mitogen-activated protein kinases, Wnt, PI3K/AKT, and NF-kappaB (nuclear factor kappa-light-chain-enhancer of activated B cells) signalling pathways might be involved in STIP-mediated tumour regulation. Collectively, these results suggest that STIP may be a novel potential diagnostic and therapeutic target for NSCLC. PMID- 26354854 TI - Improving the electro-transformation efficiency of Corynebacterium glutamicum by weakening its cell wall and increasing the cytoplasmic membrane fluidity. AB - OBJECTIVE: To improve the transformation efficiency of Corynebacterium glutamicum cells with heterogenous plasmid DNA and single-strand DNA (ssDNA) using a methodology based on electro-transformation. RESULTS: A semicomplex hypertonic medium was selected with addition of glycine and DL-threonine to weaken cell walls and addition of Tween 80 and isonicotinic acid hydrazide to increase cytoplasmic membrane fluidity. Their contents were optimized by response surface methodology. Cell growth, electro-transformation buffer, and transformation protocol were also optimized. Temporary heating inactivation of the host restriction enzyme showed a significant effect. Finally, a high transformation efficiency of 3.57 +/- 0.13 * 10(7) cfu/MUg DNA of plasmid and 1.05 * 10(6) Str (R) cfu per 10(9) viable cells with a ssDNA was achieved. CONCLUSION: The results shed light on the application in functional genomics and genome editing of C. glutamicum. PMID- 26354853 TI - Hydrolysis of plasmalogen by phospholipase A1 from Streptomyces albidoflavus for early detection of dementia and arteriosclerosis. AB - OBJECTIVES: To obtain an ethanolamine plasmalogen (PlsEtn)-hydrolyzing enzyme and to develop an assay that would help determine PlsEtn concentrations in human serum as an indicator of Alzheimer-type dementia and of arteriosclerosis. RESULTS: Phospholipase A1s, SaPLA1 and SvPLA1 from, respectively, Streptomyces albidoflavus NA297 and S. avermitilis JCM5070-but not phospholipase B from Streptomyces sp. NA684, PLA2-Nagase from S. avermitilis, PLA2IIL from S. violaceoruber nor LIPOMOD 699L (porcine phospholipase)-hydrolyzed choline plasmalogen (PlsCho) and PlsEtn (PlsCho preferred over PlsEtn). Using a combination of SaPLA1, lysoplasmalogen-specific phospholipase D (LyPls-PLD), with amine oxidase, an end-point assay was developed for measuring serum PlsEtn concentration. The standard curve, generated using various amounts of PlsEtn in this assay, was linear between 0 and 0.2 mM. PlsEtn concentrations in forty-seven serum samples, determined independently by this enzyme-based assay and (125)I HPLC method, exhibited a linear relationship, indicating that the assay is suitable for fast and accurate measurement of serum PlsEtn concentration. CONCLUSIONS: An assay, developed using SaPLA1, LyPls-PLD, and AOX, selectively measured PlsEtn levels in blood samples. This assay could be a useful diagnostic tool for early stage detection of diseases such as Alzheimer-type dementia and arteriosclerosis. PMID- 26354855 TI - Stereoselective yeast-mediated reduction of trans-5-(1'-oxo-3'-methylbutyl)-3 methyldihydrofuran-2-one: production of chiral intermediates for the synthesis of beta-secretase inhibitors. AB - OBJECTIVE: To investigate the usefulness of yeast strains to the production of chiral hydroxylactones, important synthons in the synthesis of beta-secretase inhibitors. RESULTS: Strains Rhodotorula glutinis KCh 242, Rhodotorula rubra KCh 82, Rhodotorula marina KCh 77 and Saccharomyces cerevisiae KCh 464 reduced racemic trans-5-(1'-oxo-3'-methylbutyl)-3-methyldihydrofuran-2-one (4) according to the Prelog's rule to afford preferentially the stereoisomers with S configurations at C-1'. R. marina KCh 77 and R. glutinis KCh 242 exhibited selectivity towards 3S, 5R enantiomer of the substrate, whereas R. rubra KCh 82 and S. cerevisiae KCh 464 preferred the reduction of its antipode. The highest yield of 3R,5S,1'S-hydroxylactone 3c (78 %) was obtained with R. rubra KCh 82. CONCLUSIONS: Different stereoisomers of trans-5-(1'-hydroxy-3'-methylbutyl)-3 methyldihydrofuran-2-one and its 5-substituted analogues are produced as important intermediates in the synthesis of drugs for the therapy of Alzheimer's disease. PMID- 26354856 TI - Enhancing saccharification of wheat straw by mixing enzymes from genetically modified Trichoderma reesei and Aspergillus niger. AB - OBJECTIVES: To increase the efficiency of enzymatic hydrolysis for plant biomass conversion into renewable biofuel and chemicals. RESULTS: By overexpressing the point mutation A824 V transcriptional activator Xyr1 in Trichoderma reesei, carboxymethyl cellulase, cellobiosidase and beta-D-glucosidase activities of the best mutant were increased from 1.8 IU/ml, 0.1 IU/ml and 0.05 IU/ml to 4.8 IU/ml, 0.4 IU/ml and 0.3 IU/ml, respectively. The sugar yield of wheat straw saccharification by combining enzymes from this mutant and the Aspergillus niger genetically modified strain DeltacreA/xlnR c/araR c was improved up to 7.5 mg/ml, a 229 % increase compared to the combination of wild type strains. CONCLUSIONS: Mixing enzymes from T. reesei and A. niger combined with the genetic modification of transcription factors is a promising strategy to increase saccharification efficiency. PMID- 26354857 TI - Histidine-rich glycoprotein binds DNA and RNA and attenuates their capacity to activate the intrinsic coagulation pathway. AB - When triggered by factor (F) XII and nucleic acids, we showed that thrombosis in HRG-deficient mice is accelerated compared with that in wild-type mice. In this study, we set out to identify the mechanisms by which nucleic acids promote contact activation, and to determine whether HRG attenuates their effects. DNA or RNA addition to human plasma enhances thrombin generation via the intrinsic pathway and shortens the clotting time. Their effect on the clotting time is seven- to 14-fold greater in HRG-deficient plasma than in control plasma. Investigations into the mechanisms of activation reveal that nucleic acids a) promote FXII activation in the presence of prekallikrein- and high molecular weight kininogen (HK), and b) enhance thrombin-mediated FXI activation by 10- to 12-fold. Surface plasmon resonance studies show that DNA and RNA bind FXII, FXIIa, HK, FXI, FXIa and thrombin with high affinity. HRG attenuates DNA- and RNA mediated FXII activation, and FXI activation by FXIIa or by thrombin, suggesting that HRG down regulates the capacity of DNA and RNA to activate the intrinsic pathway. Therefore, HRG attenuates the procoagulant activity of nucleic acids at multiple levels. PMID- 26354858 TI - Performance of the Automated Neuropsychological Assessment Metrics (ANAM) in detecting cognitive impairment in heart failure patients. AB - OBJECTIVE: Evaluate capacity of the Automated Neuropsychological Assessment Metrics (ANAM) to detect cognitive impairment (CI) in heart failure (HF) patients. BACKGROUND: CI is a key prognostic marker in HF. Though the most widely used cognitive screen in HF, the Mini-Mental State Examination (MMSE) is insufficiently sensitive. The ANAM has demonstrated sensitivity to cognitive domains affected by HF, but has not been assessed in this population. METHODS: Investigators administered the ANAM and MMSE to 57 HF patients, compared against a composite model of cognitive function. RESULTS: ANAM efficiency (p < .05) and accuracy scores (p < .001) successfully differentiated CI and non-CI. ANAM efficiency and accuracy scores classified 97.7% and 93.0% of non-CI patients, and 14.3% and 21.4% with CI, respectively. CONCLUSIONS: The ANAM is more effective than the MMSE for detecting CI, but further research is needed to develop a more optimal cognitive screen for routine use in HF patients. PMID- 26354859 TI - Quality of care and resource use among mechanically ventilated patients before and after an intervention to assist nurse-nonvocal patient communication. AB - OBJECTIVES: Implement and test unit-wide patient-nurse assisted communication strategies (SPEACS). BACKGROUND: SPEACS improved nurse-patient communication outcomes; effects on patient care quality and resource use are unknown. METHODS: Prospective, randomized stepped-wedge pragmatic trial of 1440 adults ventilated >=2 days and awake for at least one shift in 6 ICUs at 2 teaching hospitals 2009 2011 with blinded retrospective medical record abstraction. MAIN RESULTS: 323/383 (84%) nurses completed training; their communication knowledge (p < .001) and satisfaction and comfort (p < .001) increased. ICU days with physical restraint use (p = .44), heavy sedation (p = .73), pain score documentation (p = .97), presence of ICU-acquired pressure ulcers (p = .78), coma-free days (p = .76), ventilator-free days (p = .83), ICU length of stay (p = .77), hospital length of stay (p = .22), and median costs (p = .07) did not change. CONCLUSIONS: SPEACS improved ICU nurses' knowledge, satisfaction and comfort in communicating with nonvocal MV patients but did not impact patient care quality or resource use. PMID- 26354860 TI - Assignment of Weight-Based Antibody Units for Seven Additional Serotypes to a Human Pneumococcal Standard Reference Serum, 007sp. AB - The pneumococcal enzyme-linked immunosorbent assay (ELISA) reference standard serum, lot 89SF, has been in use since 1990 and was replaced in 2013 with a new reference standard, 007sp, that is projected to be available for the next 25 years. 007sp was generated under an FDA-approved clinical protocol; 278 adult volunteers were immunized with the 23-valent unconjugated polysaccharide vaccine Pneumovax II, and a unit of blood was obtained twice from each immunized subject within 120 days following immunization. Pooled serum was prepared from the plasma of 262 subjects, filled at 6 ml per vial, and lyophilized. Five independent laboratories participated in bridging the serotype-specific IgG assignments for 89SF to the new reference standard, 007sp, to establish equivalent reference values for 13 pneumococcal capsular serotypes (1,3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) by using the WHO reference ELISA. In a second study involving three laboratories, a similar protocol was used to assign weight-based IgG concentrations in micrograms per ml to 007sp of seven serotypes (8, 10A, 11A, 12F, 15B, 22F, and 33F) also present in the 23-valent pneumococcal unconjugated polysaccharide vaccine. In addition, the IgG assignments for a 12-member WHO quality control (QC) serum panel were also extended to cover these seven serotypes. Agreement was excellent, with a concordance correlation coefficient (r(c)) of >0.996 when each laboratory was compared to the assigned values for the 12 WHO QC serum samples. There are four remaining pneumococcal serotypes (2, 9N, 17F, and 20) found in Pneumovax II for which IgG assignments exist for 89SF and remain to be bridged. PMID- 26354861 TI - A legion of potential regulatory sRNAs exists beyond the typical microRNAs microcosm. AB - Post ENCODE, regulatory sRNAs (rsRNAs) like miRNAs have established their status as one of the core regulatory elements of cell systems. However, large number of rsRNAs are compromised due to traditional approaches to identify miRNAs, limiting the otherwise vast world of rsRNAs mainly to hair-pin loop bred typical miRNAs. The present study has analyzed for the first time a huge volume of sequencing data from 4997 individuals and 25 cancer types to report 11 234 potentially regulatory small RNAs which appear to have deep reaching impact. The rsRNA-target interactions have been studied and validated extensively using experimental data from AGO-crosslinking, DGCR8 knockdown, CLASH, proteome and expression data. A subset of such interactions was also validated independently in the present study using multiple cell lines, by qPCR. Several of the potential rsRNAs have emerged as a critical cancer biomarker controlling some important spots of cell system. The entire study has been presented into an interactive info-analysis portal handling more than 260 GB of processed data. The possible degree of cell system regulation by sRNAs appears to be much higher than previously assumed. PMID- 26354863 TI - Mitochondrial poly(A) polymerase is involved in tRNA repair. AB - Transcription of the mitochondrial genome results in polycistronic precursors, which are processed mainly by the release of tRNAs interspersed between rRNAs and mRNAs. In many metazoan mitochondrial genomes some tRNA genes overlap with downstream genes; in the case of human mitochondria the genes for tRNA(Tyr) and tRNA(Cys) overlap by one nucleotide. It has previously been shown that processing of the common precursor releases an incomplete tRNA(Tyr) lacking the 3' adenosine. The 3'-terminal adenosine has to be added before addition of the CCA end and subsequent aminoacylation. We show that the mitochondrial poly(A) polymerase (mtPAP) is responsible for this A addition. In vitro, a tRNA(Tyr) lacking the discriminator is a substrate for mtPAP. In vivo, an altered mtPAP protein level affected tRNA(Tyr) maturation, as shown by sequencing the 3' ends of mitochondrial tRNAs. Complete repair could be reconstituted in vitro with three enzymes: mtPAP frequently added more than one A to the 3' end of the truncated tRNA, and either the mitochondrial deadenylase PDE12 or the endonuclease RNase Z trimmed the oligo(A) tail to a single A before CCA addition. An enzyme machinery that evolved primarily for other purposes thus allows to tolerate the frequent evolutionary occurrence of gene overlaps. PMID- 26354862 TI - Nucleolin stabilizes G-quadruplex structures folded by the LTR promoter and silences HIV-1 viral transcription. AB - Folding of the LTR promoter into dynamic G-quadruplex conformations has been shown to suppress its transcriptional activity in HIV-1. Here we sought to identify the proteins that control the folding of this region of proviral genome by inducing/stabilizing G-quadruplex structures. The implementation of electrophorethic mobility shift assay and pull-down experiments coupled with mass spectrometric analysis revealed that the cellular protein nucleolin is able to specifically recognize G-quadruplex structures present in the LTR promoter. Nucleolin recognized with high affinity and specificity the majority, but not all the possible G-quadruplexes folded by this sequence. In addition, it displayed greater binding preference towards DNA than RNA G-quadruplexes, thus indicating two levels of selectivity based on the sequence and nature of the target. The interaction translated into stabilization of the LTR G-quadruplexes and increased promoter silencing activity; in contrast, disruption of nucleolin binding in cells by both siRNAs and a nucleolin binding aptamer greatly increased LTR promoter activity. These data indicate that nucleolin possesses a specific and regulated activity toward the HIV-1 LTR promoter, which is mediated by G quadruplexes. These observations provide new essential insights into viral transcription and a possible low mutagenic target for antiretroviral therapy. PMID- 26354864 TI - Effects of non-CpG site methylation on DNA thermal stability: a fluorescence study. AB - Cytosine methylation is a widespread epigenetic regulation mechanism. In healthy mature cells, methylation occurs at CpG dinucleotides within promoters, where it primarily silences gene expression by modifying the binding affinity of transcription factors to the promoters. Conversely, a recent study showed that in stem cells and cancer cell precursors, methylation also occurs at non-CpG pairs and involves introns and even gene bodies. The epigenetic role of such methylations and the molecular mechanisms by which they induce gene regulation remain elusive. The topology of both physiological and aberrant non-CpG methylation patterns still has to be detailed and could be revealed by using the differential stability of the duplexes formed between site-specific oligonucleotide probes and the corresponding methylated regions of genomic DNA. Here, we present a systematic study of the thermal stability of a DNA oligonucleotide sequence as a function of the number and position of non-CpG methylation sites. The melting temperatures were determined by monitoring the fluorescence of donor-acceptor dual-labelled oligonucleotides at various temperatures. An empirical model that estimates the methylation-induced variations in the standard values of hybridization entropy and enthalpy was developed. PMID- 26354866 TI - Neurophysiological evidence for diminished monitoring of own, but intact monitoring of other's errors in schizophrenia. AB - Schizophrenia is characterized by social deficits. Correctly monitoring own and others' performance is crucial for efficient social behavior. Deficits in monitoring own performance as reflected in reduced error-related negativity (rERN) amplitudes, have been demonstrated repeatedly in schizophrenia. A similar ERP component (observed ERN; oERN) is elicited when observing others' mistakes. However, possible deficits in monitoring others' performance have never been investigated in schizophrenia. The current ERP-study compared a group of schizophrenia patients (N=22) and healthy controls (N=21) while performing a Simon task and the social Simon task, enabling the investigation of own (rERN) and others' (oERN) performance monitoring. Patients showed slower reaction times, but comparable accuracy and compatibility effects in both tasks. As expected, patients' rERN amplitudes were reduced. Importantly however, oERN amplitudes were comparable between both groups. While monitoring own performance is compromised in schizophrenia, monitoring others' performance seems intact. This divergence between internal and external performance monitoring in patients is in line with studies showing normal neurophysiological responses to negative feedback. The presently found dissociation may improve our understanding of cognitive and neural mechanisms underlying monitoring of own and others' performance and may stimulate treatment development aimed at learning from external rather than internal error information in schizophrenia. PMID- 26354865 TI - Mammalian RAD51 paralogs protect nascent DNA at stalled forks and mediate replication restart. AB - Mammalian RAD51 paralogs are implicated in the repair of collapsed replication forks by homologous recombination. However, their physiological roles in replication fork maintenance prior to fork collapse remain obscure. Here, we report on the role of RAD51 paralogs in short-term replicative stress devoid of DSBs. We show that RAD51 paralogs localize to nascent DNA and common fragile sites upon replication fork stalling. Strikingly, RAD51 paralogs deficient cells exhibit elevated levels of 53BP1 nuclear bodies and increased DSB formation, the latter being attributed to extensive degradation of nascent DNA at stalled forks. RAD51C and XRCC3 promote the restart of stalled replication in an ATP hydrolysis dependent manner by disengaging RAD51 and other RAD51 paralogs from the halted forks. Notably, we find that Fanconi anemia (FA)-like disorder and breast and ovarian cancer patient derived mutations of RAD51C fails to protect replication fork, exhibit under-replicated genomic regions and elevated micro-nucleation. Taken together, RAD51 paralogs prevent degradation of stalled forks and promote the restart of halted replication to avoid replication fork collapse, thereby maintaining genomic integrity and suppressing tumorigenesis. PMID- 26354867 TI - Epidemiology of febrile seizures and epilepsy: a call for action. PMID- 26354868 TI - Chronic obstructive pulmonary diseases in children. AB - OBJECTIVES: To verify and describe the main events related to the diagnosis and management of chronic obstructive pulmonary diseases in children (COPDC) and adolescents, considering the interrelated physiopathology, genetic, and environmental characteristics. SOURCES: Relevant literature from PubMed was selected and reviewed. SUMMARY OF THE FINDINGS: COPDC have an environmental and/or genetic origin and its manifestation has manifold genotypes, phenotypes, and endotypes. Although COPDC has no cure, it can be clinically controlled. Chronic cough is the main symptom and bronchiectasis can be present in several COPDC patients. The management of COPDC is more effective if based on guidelines and when treatment regimen adherence is promoted. Oral and inhaled corticosteroids, bronchodilators, inhaled antibiotics, and treatment of pulmonary exacerbation (PE) are the bases of COPDC management, and should be individualized for each patient. CONCLUSIONS: Correct diagnosis and knowledge of risk factors and comorbidities are essential in COPDC management. Procedures and drugs used should be based on specific guidelines for each COPDC case. Treatment adherence is critical to obtain the benefits of management. COPDC clinical control must be evaluated by the decrease in PEs, improved quality of life, reduction of pulmonary function loss, and lung structural damage. For most cases of COPDC, monitoring by interdisciplinary teams in specialized reference centers with surveillance strategies and continuous care leads to better outcomes, which must be evaluated by decreasing pulmonary function damage and deterioration, better prognosis, better quality life, and increased life expectancy. PMID- 26354869 TI - Use of macrolides in lung diseases: recent literature controversies. AB - OBJECTIVE: To review the mechanisms of action of macrolides in pediatric respiratory diseases and their clinical indications. SOURCES: Review in the PubMed database, comprising the following terms in English: "macrolide and asthma"; "macrolide and cystic fibrosis"; "macrolide bronchiolitis and viral acute"; "macrolide and bronchiolitis obliterans" and "macrolide and non-CF bronchiectasis". SUMMARY OF THE FINDINGS: The spectrum of action of macrolides includes production of inflammatory mediators, control of mucus hypersecretion, and modulation of host-defense mechanisms. The potential benefit of macrolide antibiotics has been studied in a variety of lung diseases, such as cystic fibrosis (CF), bronchiectasis, asthma, acute bronchiolitis, and non-CF bronchiectasis. Several studies have evaluated the benefits of macrolides in asthma refractory to therapy, but the results are controversial and indications should be limited to specific phenotypes. In viral bronchiolitis, there is no consistent benefit in acute conditions, although recent data have shown an effect in recurrent wheezing prevention. In patients with CF results are also contradictory, but the consensus states there is a small clinical benefit, especially for patients infected with P. aeruginosa. There was also no positive action of macrolides in patients with post-infectious bronchiolitis obliterans. Children with non-CF bronchiectasis seem to have clear benefits regarding the use of macrolides, which showed clinical advantages in parenchyma protection and lung function. CONCLUSIONS: The long-term use of macrolides should be limited to highly selected situations, especially in patients with bronchiectasis. Careful evaluation of the benefits and potential damage are tools for their indication in specific groups. PMID- 26354870 TI - The road to eliminate mother-to-child HIV transmission. PMID- 26354871 TI - Hypothermia therapy for newborns with hypoxic ischemic encephalopathy. AB - OBJECTIVE: Therapeutic hypothermia reduces cerebral injury and improves the neurological outcome secondary to hypoxic ischemic encephalopathy in newborns. It has been indicated for asphyxiated full-term or near-term newborn infants with clinical signs of hypoxic-ischemic encephalopathy (HIE). SOURCES: A search was performed for articles on therapeutic hypothermia in newborns with perinatal asphyxia in PubMed; the authors chose those considered most significant. SUMMARY OF THE FINDINGS: There are two therapeutic hypothermia methods: selective head cooling and total body cooling. The target body temperature is 34.5 degrees C for selective head cooling and 33.5 degrees C for total body cooling. Temperatures lower than 32 degrees C are less neuroprotective, and temperatures below 30 degrees C are very dangerous, with severe complications. Therapeutic hypothermia must start within the first 6h after birth, as studies have shown that this represents the therapeutic window for the hypoxic-ischemic event. Therapy must be maintained for 72 h, with very strict control of the newborn's body temperature. It has been shown that therapeutic hypothermia is effective in reducing neurologic impairment, especially in full-term or near-term newborns with moderate hypoxic-ischemic encephalopathy. CONCLUSION: Therapeutic hypothermia is a neuroprotective technique indicated for newborn infants with perinatal asphyxia and hypoxic-ischemic encephalopathy. PMID- 26354872 TI - Update on diagnosis and management of childhood epilepsies. AB - OBJECTIVES: To review the current evidence base for the diagnosis and management of the childhood epilepsies and to draw attention to the current gaps in this evidence base. The focus will be on therapeutic aspects. Current International League Against Epilepsy (ILAE) terminology will be described and used throughout the discussion. The review will draw attention to recent advances that have been made in both our understanding and treatment of the childhood epilepsies. Potential future directions for research and treatment options will be discussed. SOURCES: Original articles relevant to the subject were obtained from the MedLine database using pertinent MeSH terms. Relevant papers were read and assimilated. Citation searching was used. SUMMARY OF THE FINDINGS: Epilepsy is a major cause of global disease burden. Childhood epilepsies are a heterogeneous group of conditions. A multi-axial diagnostic approach should be taken prior to making treatment and management decisions for any individual patient. For the majority of patients, successful control of seizures can be achieved with a single medication. However, a significant minority develops refractory disease. Epilepsy surgery can provide cure for a carefully selected group of these cases. CONCLUSIONS: There remain significant gaps the evidence base for treatment in several areas of childhood epilepsy. Concerted multi-center efforts should be made to try to close these gaps. A personalized medicine approach may help to reduce the proportion of refractory cases of childhood epilepsy in future. PMID- 26354873 TI - Development of the Role and Scope of an Academic Mentorship Network for Health Professionals Working with People with Rheumatological and Musculoskeletal Conditions across Europe. PMID- 26354874 TI - Radiation Exposure in Imaging of Suspected Child Abuse: Benefits versus Risks. PMID- 26354875 TI - Rhein antagonizes P2X7 receptor in rat peritoneal macrophages. AB - P2X7 receptor plays important roles in inflammation and immunity, and thereby it serves as a potential therapeutic target for inflammatory diseases. Rhein, an anthraquinone derivative, exhibits significant anti-inflammatory and immunosuppressive activities in therapy. However, the underlying mechanisms are largely unclear. Here, we aimed to investigate the effects of rhein on P2X7 receptor-mediated responses in vitro. In HEK293 cells expressing rat P2X7 receptor, we first found that rhein concentration-dependently blocked ATP-induced cytosolic calcium concentration ([Ca(2+)]c) elevation and pore formation of the plasma membrane, two hallmarks of the P2X7 receptor activation. These two inhibitory effects of rhein were also observed in rat peritoneal macrophages. Furthermore, rhein counteracted macrophage phagocytosis attenuation and suppressed reactive oxygen species (ROS) production triggered by ATP/BzATP. Meanwhile, rhein reduced ATP/BzATP-induced IL-1beta release in lipopolysaccharide activated macrophages. Prolonged application of ATP caused macrophage apoptosis, while the presence of rhein suppressed this cell cytotoxicity. Such ATP/BzATP induced cellular reactions were also inhibited by a well-known rat P2X7 receptor antagonist, brilliant blue G, in a similar way to rhein. Together, our results demonstrate that rhein inhibit ATP/BzATP-induced [Ca(2+)]c increase, pore formation, ROS production, phagocytosis attenuation, IL-1beta release and cell apoptosis by antagonizing the P2X7 receptor in rat peritoneal macrophages. PMID- 26354876 TI - Ultraviolet light converts propranolol, a nonselective beta-blocker and potential lupus-inducing drug, into a proinflammatory AhR ligand. AB - UV light and some medications are known to trigger lupus erythematosus (LE). A common mechanism underlying the immunopathologic effect, resulting from exposure to these two seemingly unrelated factors, remains unknown. The aryl hydrocarbon receptor (AhR) plays a key role in the regulation of IL-22 production in humans and can be activated by both xenobiotics and naturally occurring photoproducts. A significant expansion of Th17 and Th22 cells was observed in the peripheral blood of active systemic LE (SLE) patients, compared to inactive patients and controls. We also show that propranolol, a potential lupus-inducing drug, induced stronger AhR activation in PBMCs of SLE patients than in those of controls. AhR agonist activity of propranolol was enhanced by UV light exposure. MS analysis of irradiated propranolol revealed the generation of a proinflammatory photoproduct. This compound behaves like the prototypic AhR ligand 6-formylindolo[3,2 b]carbazole, a cutaneous UV light-induced tryptophan metabolite, both promoting IL-22, IL-8, and CCL2 secretion by T-cells and macrophages. Finally, LE patients exhibit signs of cutaneous AhR activation that correlate with lesional expression of the same proinflammatory cytokines, suggesting a role for photometabolites in the induction of skin inflammation. The AhR might therefore represent a target for therapeutic intervention in LE. PMID- 26354877 TI - Genetics of Venous Thrombosis: update in 2015. AB - Venous thrombosis (VT) is a common multifactorial disease with a genetic component that was first suspected nearly 60 years ago. In this review, we document the genetic determinants of the disease, and update recent findings delivered by the application of high-throughput genotyping and sequencing technologies. To date, 17 genes have been robustly demonstrated to harbour genetic variations associated with VT risk: ABO, F2, F5, F9, F11, FGG, GP6, KNG1, PROC, PROCR, PROS1, SERPINC1, SLC44A2, STXBP5, THBD, TSPAN15 and VWF. The common polymorphisms are estimated to account only for a modest part (~5 %) of the VT heritability. Much remains to be done to fully disentangle the exact genetic (and epigenetic) architecture of the disease. A large suite of powerful tools and research strategies can be deployed on the large collections of patients that have already been assembled (and additional are ongoing). PMID- 26354878 TI - Facile microfluidic channels for acoustophoresis on a budget. AB - Acoustophoresis is a powerful yet gentle technique for manipulating cells and particles that has quickly earned a place in the lab-on-a-chip toolkit. However, traditional construction techniques for acoustophoretic resonators have typically required prohibitively expensive and laborious processing methods. Here, we propose a highly cost-effective and cleanroom-free construction technique for transversal acoustophoretic resonators. Channels with two different widths of 750 and 300 MUm were constructed using a simple glass and polyimide sandwiching technique. Half and full wavelength resonators were then established using 1 and 5 MHz ultrasound respectively and polystyrene beads were successfully manipulated in both types of resonators. This construction technique was then utilized to demonstrate a bifurcation and trifurcation microchannel with 600 MUm widths and 2.5 MHz ultrasound. Our approach addresses some of the key drawbacks of acoustophoretic devices by drastically simplifying the fabrication and prototyping of transversal resonators and will assist in expanding this technology from laboratory benches and into the broader market. PMID- 26354879 TI - Integrin associated proteins differentially regulate neutrophil polarity and directed migration in 2D and 3D. AB - Directed neutrophil migration in blood vessels and tissues is critical for proper immune function; however, the mechanisms that regulate three-dimensional neutrophil chemotaxis remain unclear. It has been shown that integrins are dispensable for interstitial three-dimensional (3D) leukocyte migration; however, the role of integrin regulatory proteins during directed neutrophil migration is not known. Using a novel microfluidic gradient generator amenable to 2D and 3D analysis, we found that the integrin regulatory proteins Kindlin-3, RIAM, and talin-1 differentially regulate neutrophil polarization and directed migration to gradients of chemoattractant in 2D versus 3D. Both talin-1-deficient and RIAM deficient neutrophil-like cells had impaired adhesion, polarization, and migration on 2D surfaces whereas in 3D the cells polarized but had impaired 3D chemotactic velocity. Kindlin-3 deficient cells were able to polarize and migrate on 2D surfaces but had impaired directionality. In a 3D environment, Kindlin-3 deficient cells displayed efficient chemotaxis. These findings demonstrate that the role of integrin regulatory proteins in cell polarity and directed migration can be different in 2D and 3D. PMID- 26354880 TI - Acute generalized exanthematous pustulosis (AGEP): A review and update. AB - Acute generalized exanthematous pustulosis is a severe cutaneous adverse reaction characterized by the rapid development of nonfollicular, sterile pustules on an erythematous base. It is attributed to drugs in the majority of cases. Antibiotics are the most common cause of acute generalized exanthematous pustulosis; however, a wide variety of drugs has been associated with this condition. Typically, within 48 hours of ingesting the causative medication, there is acute onset of fever and pustulosis with leukocytosis. In severe cases there can be mucous membrane and systemic organ involvement. Histologic findings include intracorneal, subcorneal, and/or intraepidermal pustules with papillary dermal edema containing neutrophils and eosinophils. Treatment focuses on removal of the causative drug, supportive care, infection prevention, and the often beneficial use of a potent topical steroid. PMID- 26354882 TI - Long-term impact of CMV infection on allografts and on patient survival in renal transplant patients with protocol biopsies. AB - Cytomegalovirus (CMV) infection is a frequent complication of early posttransplantation. This study examines its impact on chronic allograft changes, long-term graft loss, and patient survival. We studied 594 patients who had protocol biopsies at 6 wk, and 3 and 6 mo posttransplantation. Chronic allograft changes were evaluated according to the updated Banff classification [interstitial fibrosis/tubular atrophy (IF/TA), vascular and glomerular lesions]. Follow-up data were available for up to 10 yr. CMV infection was diagnosed in 153 of 594 patients (26%) in the first year after transplantation, mostly within the first 3 mo. Graft survival was reduced in patients with CMV (P = 0.03) as well as the combined allograft/patient survival (P = 0.008). Prevalence of IF/TA at 6 wk after transplantation was already threefold higher in patients who experienced CMV infection later on compared with patients without CMV (P = 0.005). In multivariate analyses, CMV viremia or disease was not a significant factor for graft loss or death. In conclusion, patients with CMV infection posttransplantation show more chronic allograft changes early on, even before CMV infection, and development of IF/TA is not more prevalent in patients with CMV. Our data do not support a significant role of CMV in patient and graft outcomes. PMID- 26354883 TI - Re: Clinical Outcomes of cT1 Micropapillary Bladder Cancer: D. L. Willis, M. I. Fernandez, R. J. Dickstein, S. Parikh, J. B. Shah, L. L. Pisters, C. C. Guo, S. Henderson, B. A. Czerniak, H. B. Grossman, C. P. Dinney and A. M. Kamat J Urol 2015;193:1129-1134. PMID- 26354881 TI - Renal sodium-glucose cotransporter inhibition in the management of type 2 diabetes mellitus. AB - Hyperglycemia is the primary factor responsible for the microvascular, and to a lesser extent macrovascular, complications of diabetes. Despite this well established relationship, approximately half of all type 2 diabetic patients in the US have a hemoglobin A1c (HbA1c) >=7.0%. This is associated in part with the side effects, i.e., weight gain and hypoglycemia, of currently available antidiabetic agents and in part with the failure to utilize medications that reverse the basic pathophysiological defects present in patients with type 2 diabetes. The kidney has been shown to play a central role in the development of hyperglycemia by excessive production of glucose throughout the sleeping hours and enhanced reabsorption of filtered glucose by the renal tubules secondary to an increase in the threshold at which glucose spills into the urine. Recently, a new class of antidiabetic agents, the sodium-glucose cotransporter 2 (SGLT2) inhibitors, has been developed and approved for the treatment of patients with type 2 diabetes. In this review, we examine their mechanism of action, efficacy, safety, and place in the therapeutic armamentarium. Since the SGLT2 inhibitors have a unique mode of action that differs from all other oral and injectable antidiabetic agents, they can be used at all stages of the disease and in combination with all other antidiabetic medications. PMID- 26354884 TI - Re: Cross-Sectional Study of Determinants of Upper and Lower Urinary Tract Outcomes in Adults with Spinal Dysraphism--New Recommendations for Urodynamic Followup Guidelines?: P. W. Veenboer, J. L. Bosch, P. F. Rosier, P. Dik, F. W. van Asbeck, T. P. de Jong and L. M. de Kort J Urol 2014;192:477-482. PMID- 26354885 TI - Reply by Authors. PMID- 26354886 TI - Re: The Prostate Health Index Selectively Identifies Clinically Significant Prostate Cancer: S. Loeb, M. G. Sanda, D. L. Broyles, S. S. Shin, C. H. Bangma, J. T. Wei, A. W. Partin, G. G. Klee, K. M. Slawin, L. S. Marks, R. H. N. van Schaik, D. W. Chan, L. J. Sokoll, A. B. Cruz, I. A. Mizrahi and W. J. Catalona J Urol 2015;193:1163-1169. PMID- 26354887 TI - Re: The Artificial Somato-Autonomic Reflex Arch Does Not Improve Lower Urinary Tract Function in Patients with Spinal Cord Lesions: M. M. Rasmussen, Y. F. Rawashdeh, D. Clemmensen, H. Tankisi, A. Fuglsang-Frederiksen, K. Krogh and P. Christensen J Urol 2015;193:598-604. PMID- 26354888 TI - Reply by Authors. PMID- 26354889 TI - Reply by Authors. PMID- 26354890 TI - Integrated care programs for patients with psychological comorbidity: A systematic review and meta-analysis. AB - OBJECTIVE: Presently, little is known about the characteristics and impact of integrated care programs for patients with psychological comorbidity. The aim was to provide an overview of these integrated care programs and their effectiveness. METHODS: Systematic literature review including papers published between 1995 and 2014. An integrated care program had to consist of interventions related to at least two out of the six components of the Chronic Care Model. Programs had to address patients with psychological comorbidity, which is a psychological disease next to a somatic chronic disease. A meta-analysis was performed on depression treatment response and a best evidence synthesis was performed on other outcomes. RESULTS: Ten programs were identified, which mostly addressed comorbid depression and consisted of interventions related to three to five components of the Chronic Care Model. Meta-analysis showed significantly higher odds for depression treatment response for patients receiving integrated care (OR: 2.49, 95%CI [1.66 3.75]). Best evidence synthesis suggested moderate evidence for cost effectiveness and for a beneficial effect on patient satisfaction and emotional well-being. Insufficient evidence was found for a beneficial effect on health related quality of life, medication adherence, Hb1Ac levels and mortality. CONCLUSION: There are few studies evaluating integrated care programs for patients with psychological comorbidity. Although these studies suggest that integrated care programs could positively affect several patient outcomes and could be cost-effective, additional studies are recommended to further assess the value of integrated care for this patient group. This is especially important since the number of people with psychological comorbidity is rising. PMID- 26354891 TI - Metamaterial Absorber for Electromagnetic Waves in Periodic Water Droplets. AB - Perfect metamaterial absorber (PMA) can intercept electromagnetic wave harmful for body in Wi-Fi, cell phones and home appliances that we are daily using and provide stealth function that military fighter, tank and warship can avoid radar detection. We reported new concept of water droplet-based PMA absorbing perfectly electromagnetic wave with water, an eco-friendly material which is very plentiful on the earth. If arranging water droplets with particular height and diameter on material surface through the wettability of material surface, meta-properties absorbing electromagnetic wave perfectly in GHz wide-band were shown. It was possible to control absorption ratio and absorption wavelength band of electromagnetic wave according to the shape of water droplet-height and diameter- and apply to various flexible and/or transparent substrates such as plastic, glass and paper. In addition, this research examined how electromagnetic wave can be well absorbed in water droplets with low electrical conductivity unlike metal based metamaterials inquiring highly electrical conductivity. Those results are judged to lead broad applications to variously civilian and military products in the future by providing perfect absorber of broadband in all products including transparent and bendable materials. PMID- 26354893 TI - Microglia in Health and Disease. AB - Microglia, the major myeloid cells of the central nervous system (CNS) are implicated in physiologic processes and in the pathogenesis of several CNS disorders. Since their initial description early in the 20th century, our ability to identify and isolate microglia has significantly improved and new research is providing insight into the functions of these cells in sickness and in health. Here, we review recent advances in our understanding of the role of microglia in physiological and pathological processes of the CNS with a focus on multiple sclerosis and Alzheimer's disease. Because of the prominent roles CX3CR1 and its ligand fractalkine played in bringing about these advances, we discuss the physiological and pathological roles of microglia as viewed from the CX3CR1 fractalkine perspective, providing a unique viewpoint. Based on the most recent studies of molecular profiling of microglia, we also propose a molecular and functional definition of microglia that incorporates the properties attributed to these cells in recent years. PMID- 26354894 TI - The Nodes of Ranvier: Molecular Assembly and Maintenance. AB - Action potential (AP) propagation in myelinated nerves requires clustered voltage gated sodium and potassium channels. These channels must be specifically localized to nodes of Ranvier where the AP is regenerated. Several mechanisms have evolved to facilitate and ensure the correct assembly and stabilization of these essential axonal domains. This review highlights the current understanding of the axon intrinsic and glial extrinsic mechanisms that control the formation and maintenance of the nodes of Ranvier in both the peripheral nervous system (PNS) and central nervous system (CNS). PMID- 26354892 TI - Fine-scale mapping of the 4q24 locus identifies two independent loci associated with breast cancer risk. AB - BACKGROUND: A recent association study identified a common variant (rs9790517) at 4q24 to be associated with breast cancer risk. Independent association signals and potential functional variants in this locus have not been explored. METHODS: We conducted a fine-mapping analysis in 55,540 breast cancer cases and 51,168 controls from the Breast Cancer Association Consortium. RESULTS: Conditional analyses identified two independent association signals among women of European ancestry, represented by rs9790517 [conditional P = 2.51 * 10(-4); OR, 1.04; 95% confidence interval (CI), 1.02-1.07] and rs77928427 (P = 1.86 * 10(-4); OR, 1.04; 95% CI, 1.02-1.07). Functional annotation using data from the Encyclopedia of DNA Elements (ENCODE) project revealed two putative functional variants, rs62331150 and rs73838678 in linkage disequilibrium (LD) with rs9790517 (r(2) >= 0.90) residing in the active promoter or enhancer, respectively, of the nearest gene, TET2. Both variants are located in DNase I hypersensitivity and transcription factor-binding sites. Using data from both The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), we showed that rs62331150 was associated with level of expression of TET2 in breast normal and tumor tissue. CONCLUSION: Our study identified two independent association signals at 4q24 in relation to breast cancer risk and suggested that observed association in this locus may be mediated through the regulation of TET2. IMPACT: Fine-mapping study with large sample size warranted for identification of independent loci for breast cancer risk. PMID- 26354895 TI - Reconsolidation and the Dynamic Nature of Memory. AB - Memory reconsolidation is the process in which reactivated long-term memory (LTM) becomes transiently sensitive to amnesic agents that are effective at consolidation. The phenomenon was first described more than 50 years ago but did not fit the dominant paradigm that posited that consolidation takes place only once per LTM item. Research on reconsolidation was revitalized only more than a decade ago with the demonstration of reconsolidation in a well-defined behavioral protocol (auditory fear conditioning in the rat) subserved by an identified brain circuit (basolateral amygdala). Since then, reconsolidation has been shown in many studies over a range of species, tasks, and amnesic agents, and cellular and molecular correlates of reconsolidation have also been identified. In this review, I will first define the evidence on which reconsolidation is based, and proceed to discuss some of the conceptual issues facing the field in determining when reconsolidation does and does not occur. Last, I will refer to the potential clinical implications of reconsolidation. PMID- 26354896 TI - Microbial Speciation. AB - What are species? How do they arise? These questions are not easy to answer and have been particularly controversial in microbiology. Yet, for those microbiologists studying environmental questions or dealing with clinical issues, the ability to name and recognize species, widely considered the fundamental units of ecology, can be practically useful. On a more fundamental level, the speciation problem, the focus here, is more mechanistic and conceptual. What is the origin of microbial species, and what evolutionary and ecological mechanisms keep them separate once they begin to diverge? To what extent are these mechanisms universal across diverse types of microbes, and more broadly across the entire the tree of life? Here, we propose that microbial speciation must be viewed in light of gene flow, which defines units of genetic similarity, and of natural selection, which defines units of phenotype and ecological function. We discuss to what extent ecological and genetic units overlap to form cohesive populations in the wild, based on recent evolutionary modeling and population genomics studies. These studies suggest a continuous "speciation spectrum," which microbial populations traverse in different ways depending on their balance of gene flow and natural selection. PMID- 26354898 TI - Large-scale phylogenetic analyses reveal multiple gains of actinorhizal nitrogen fixing symbioses in angiosperms associated with climate change. AB - Nitrogen is fundamental to all life forms and is also one of the most limiting of nutrients for plant growth. Several clades of angiosperms have developed symbiotic relationships with actinorhizal bacteria that fix atmospheric nitrogen and increase access to this nutrient. However, the evolutionary patterns of actinorhizal nitrogen-fixing symbioses remain unclear to date. Furthermore the underlying environmental pressures that led to the gain of symbiotic actinorhizal nitrogen fixation have never been investigated. Here, we present the most comprehensive genus-level phylogenetic analysis of the nitrogen-fixing angiosperms based on three plastid loci. We found that actinorhizal nitrogen fixing species are distributed in nine distinct lineages. By dating the branching events, we determined that seven actinorhizal nitrogen-fixing lineages originated during the Late Cretaceous, and two more emerged during the Eocene. We put forward a hypothesis that multiple gains of actinorhizal nitrogen-fixing symbioses in angiosperms may have been associated with increased global temperatures and high levels of atmospheric carbon dioxide during these two time periods, as well as the availability of open habitats with high light conditions. Our nearly complete genus-level time-tree for the nitrogen-fixing clade is a significant advance in understanding the evolutionary and ecological background of this important symbiosis between plants and bacteria. PMID- 26354897 TI - A systematic review of dietary, nutritional, and physical activity interventions for the prevention of prostate cancer progression and mortality. AB - PURPOSE: Given the long-term, although potentially fatal, nature of prostate cancer, there is increasing observational evidence for the reduction in disease progression and mortality through changes in lifestyle factors. METHODS: We systematically reviewed dietary, nutritional, and physical activity randomized interventions aimed at modifying prostate cancer progression and disease-specific mortality, including a detailed assessment of risk of bias and methodological quality. RESULTS: Forty-four randomized controlled trials of lifestyle interventions, with prostate cancer progression or mortality outcomes, were identified. Substantial heterogeneity of the data prevented a meta-analysis. The included trials involved 3,418 prostate cancer patients, median 64 men per trial, from 13 countries. A trial of a nutritional supplement of pomegranate seed, green tea, broccoli, and turmeric; a trial comparing flaxseed, low-fat diet, flaxseed, and low-fat diet versus usual diet; and a trial supplementing soy, lycopene, selenium, and coenzyme Q10, all demonstrated beneficial effects. These trials were also assessed as having low risk of bias and high methodological quality (as were seven other trials with no evidence of benefit). The remaining trials were either underpowered, at high or unclear risk of bias, inadequately reported, of short duration or measured surrogate outcomes of unproven relationship to mortality or disease progression, which precluded any benefits reported being reliable. CONCLUSION: Large, well-designed randomized trials with clinical endpoints are recommended for lifestyle modification interventions. PMID- 26354899 TI - Trends in Socioeconomic Inequalities in Motor Vehicle Accident Deaths in the United States, 1995-2010. AB - Motor vehicle accident (MVA) mortality has been declining overall, but little is known about trends by socioeconomic position. We examined trends in education related inequalities in US MVA death rates from 1995 to 2010. We used mortality data from the National Center for Health Statistics and population estimates from the Current Population Survey, and we calculated vehicle- and person-miles traveled using data from the National Household Travel Survey. We used negative binomial regression to estimate crude and age-, sex-, and race-adjusted mortality rates among adults aged 25 years or more. We found larger mortality decreases among the more highly educated and some evidence of mortality increases among the least educated. Adjusted death rates were 15.3 per 100,000 population (95% confidence interval (CI): 10.7, 19.9) higher at the bottom of the education distribution than at the top of the education distribution in 1995, increasing to 17.9 per 100,000 population (95% CI: 14.8, 21.0) by 2010. In relative terms, adjusted death rates were 2.4 (95% CI: 1.7, 3.0) times higher at the bottom of the education distribution than at the top in 1995, increasing to 4.3 times higher (95% CI: 3.4, 5.3) by 2010. Inequality increases were larger in terms of vehicle-miles traveled. Although overall MVA death rates declined during this period, socioeconomic differences in MVA mortality have persisted or worsened over time. PMID- 26354900 TI - Preparation of novel ionic-liquid-modified magnetic nanoparticles by a microwave assisted method for sulfonylurea herbicides extraction. AB - Ionic liquids immobilized on magnetic nanoparticles were prepared by an efficient microwave-assisted synthesis method, and the properties of the ionic liquids were tuned based on the aromatic functional modification of its anion through a simple metathesis reaction. The novel as-synthesized magnetic materials were characterized by various instrumental techniques. The magnetic nanoparticles have been utilized as adsorbents for the extraction of four sulfonylurea herbicides in tea samples, in combination with high-performance liquid chromatography analysis. Significant extraction parameters, including type and volume of desorption solvent, extraction time, amount of adsorbent, and ionic strength were investigated. Under the optimum conditions, good linearity was obtained in the concentration range of 1-150 MUg/L for metsulfuron-methyl and bensulfuron-methyl, and 3-150 MUg/L for sulfometuron-methyl and chlorimuron-ethyl, with correlation coefficients R2 > 0.9987. Low limits of detection were obtained ranging from 0.13 to 0.81 MUg/L. The relative standard deviations were 1.8-3.9%. Comparisons of extraction efficiency with conventional solid-phase extraction equipped with a commercial C18 cartridge were performed. Results indicated that magnetic solid phase extraction is simple, time-saving, efficient and inexpensive with the reusability of adsorbents. The proposed method has been successfully used to determine sulfonylurea herbicides from tea samples with satisfactory recoveries of 80.5-104.2%. PMID- 26354901 TI - The Complement Receptor C5aR Has a Dual, Time-Dependent Effect on the Outcome of Spinal Cord Injury. PMID- 26354902 TI - A Dual Role for Sleep Spindles in Sleep-Dependent Memory Consolidation? PMID- 26354903 TI - Temporary Neurotrophin Treatment Prevents Deafness-Induced Auditory Nerve Degeneration and Preserves Function. AB - After substantial loss of cochlear hair cells, exogenous neurotrophins prevent degeneration of the auditory nerve. Because cochlear implantation, the current therapy for profound sensorineural hearing loss, depends on a functional nerve, application of neurotrophins is being investigated. We addressed two questions important for fundamental insight into the effects of exogenous neurotrophins on a degenerating neural system, and for translation to the clinic. First, does temporary treatment with brain-derived neurotrophic factor (BDNF) prevent nerve degeneration on the long term? Second, how does a BDNF-treated nerve respond to electrical stimulation? Deafened guinea pigs received a cochlear implant, and their cochleas were infused with BDNF for 4 weeks. Up to 8 weeks after treatment, their cochleas were analyzed histologically. Electrically evoked compound action potentials (eCAPs) were recorded using stimulation paradigms that are informative of neural survival. Spiral ganglion cell (SGC) degeneration was prevented during BDNF treatment, resulting in 1.9 times more SGCs than in deafened untreated cochleas. Importantly, SGC survival was almost complete 8 weeks after treatment cessation, when 2.6 times more SGCs were observed. In four eCAP characteristics (three involving alteration of the interphase gap of the biphasic current pulse and one involving pulse trains), we found large and statistically significant differences between normal-hearing and deaf controls. Importantly, for BDNF treated animals, these eCAP characteristics were near normal, suggesting healthy responsiveness of BDNF-treated SGCs. In conclusion, clinically practicable short term neurotrophin treatment is sufficient for long-term survival of SGCs, and it can restore or preserve SGC function well beyond the treatment period. Significance statement: Successful restoration of hearing in deaf subjects by means of a cochlear implant requires a healthy spiral ganglion cell population. Deafness-induced degeneration of these cells can be averted with neurotrophic factors. In the present study in deafened guinea pigs, we investigated the long term effects of temporary (i.e., clinically practicable) treatment with brain derived neurotrophic factor (BDNF). We show that, after treatment cessation, the neuroprotective effect remains for at least 8 weeks. Moreover, for the first time, it is shown that the electrical responsiveness of BDNF-treated spiral ganglion cells is preserved during this period as well. These findings demonstrate that treatment of the auditory nerve with neurotrophic factors may be relevant for cochlear implant users. PMID- 26354904 TI - Anatomical Organization and Spatiotemporal Firing Patterns of Layer 3 Neurons in the Rat Medial Entorhinal Cortex. AB - Layer 3 of the medial entorhinal cortex is a major gateway from the neocortex to the hippocampus. Here we addressed structure-function relationships in medial entorhinal cortex layer 3 by combining anatomical analysis with juxtacellular identification of single neurons in freely behaving rats. Anatomically, layer 3 appears as a relatively homogeneous cell sheet. Dual-retrograde neuronal tracing experiments indicate a large overlap between layer 3 pyramidal populations, which project to ipsilateral hippocampus, and the contralateral medial entorhinal cortex. These cells were intermingled within layer 3, and had similar morphological and intrinsic electrophysiological properties. Dendritic trees of layer 3 neurons largely avoided the calbindin-positive patches in layer 2. Identification of layer 3 neurons during spatial exploration (n = 17) and extracellular recordings (n = 52) pointed to homogeneous spatial discharge patterns. Layer 3 neurons showed only weak spiking theta rhythmicity and sparse head-direction selectivity. A majority of cells (50 of 69) showed no significant spatial modulation. All of the ~28% of neurons that carried significant amounts of spatial information (19 of 69) discharged in irregular spatial patterns. Thus, layer 3 spatiotemporal firing properties are remarkably different from those of layer 2, where theta rhythmicity is prominent and spatially modulated cells often discharge in grid or border patterns. Significance statement: Neurons within the superficial layers of the medial entorhinal cortex (MEC) often discharge in border, head-direction, and theta-modulated grid patterns. It is still largely unknown how defined discharge patterns relate to cellular diversity in the superficial layers of the MEC. In the present study, we addressed this issue by combining anatomical analysis with juxtacellular identification of single layer 3 neurons in freely behaving rats. We provide evidence that the anatomical organization and spatiotemporal firing properties of layer 3 neurons are remarkably different from those in layer 2. Specifically, most layer 3 neurons discharged in spatially irregular firing patterns, with weak theta-modulation and head-directional selectivity. This work thus poses constraints on the spatiotemporal patterns reaching downstream targets, like the hippocampus. PMID- 26354905 TI - The Role of the Parietal Cortex in the Representation of Task-Reward Associations. AB - Rewards obtained from specific behaviors can and do change across time. To adapt to such conditions, humans need to represent and update associations between behaviors and their outcomes. Much previous work focused on how rewards affect the processing of specific tasks. However, abstract associations between multiple potential behaviors and multiple rewards are an important basis for adaptation as well. In this experiment, we directly investigated which brain areas represent associations between multiple tasks and rewards, using time-resolved multivariate pattern analysis of functional magnetic resonance imaging data. Importantly, we were able to dissociate neural signals reflecting task-reward associations from those related to task preparation and reward expectation processes, variables that were often correlated in previous research. We hypothesized that brain regions involved in processing tasks and/or rewards will be involved in processing associations between them. Candidate areas included the dorsal anterior cingulate cortex, which is involved in associating simple actions and rewards, and the parietal cortex, which has been shown to represent task rules and action values. Our results indicate that local spatial activation patterns in the inferior parietal cortex indeed represent task-reward associations. Interestingly, the parietal cortex flexibly changes its content of representation within trials. It first represents task-reward associations, later switching to process tasks and rewards directly. These findings highlight the importance of the inferior parietal cortex in associating behaviors with their outcomes and further show that it can flexibly reconfigure its function within single trials. Significance statement: Rewards obtained from specific behaviors rarely remain constant over time. To adapt to changing conditions, humans need to continuously update and represent the current association between behavior and its outcomes. However, little is known about the neural representation of behavior-outcome associations. Here, we used multivariate pattern analysis of functional magnetic resonance imaging data to investigate the neural correlates of such associations. Our results demonstrate that the parietal cortex plays a central role in representing associations between multiple behaviors and their outcomes. They further highlight the flexibility of the parietal cortex, because we find it to adapt its function to changing task demands within trials on relatively short timescales. PMID- 26354906 TI - Resting-State Retinotopic Organization in the Absence of Retinal Input and Visual Experience. AB - Early visual areas have neuronal receptive fields that form a sampling mosaic of visual space, resulting in a series of retinotopic maps in which the same region of space is represented in multiple visual areas. It is not clear to what extent the development and maintenance of this retinotopic organization in humans depend on retinal waves and/or visual experience. We examined the corticocortical receptive field organization of resting-state BOLD data in normally sighted, early blind, and anophthalmic (in which both eyes fail to develop) individuals and found that resting-state correlations between V1 and V2/V3 were retinotopically organized for all subject groups. These results show that the gross retinotopic pattern of resting-state connectivity across V1-V3 requires neither retinal waves nor visual experience to develop and persist into adulthood. Significance statement: Evidence from resting-state BOLD data suggests that the connections between early visual areas develop and are maintained even in the absence of retinal waves and visual experience. PMID- 26354907 TI - Discrimination of Visual Categories Based on Behavioral Relevance in Widespread Regions of Frontoparietal Cortex. AB - Allocating attentional resources to currently relevant information in a dynamically changing environment is critical to goal-directed behavior. Previous studies in nonhuman primates (NHPs) have demonstrated modulation of neural representations of stimuli, in particular visual categorizations, by behavioral significance in the lateral prefrontal cortex. In the human brain, a network of frontal and parietal regions, the "multiple demand" (MD) system, is involved in cognitive and attentional control. To test for the effect of behavioral significance on categorical discrimination in the MD system in humans, we adapted a previously used task in the NHP and used multivoxel pattern analysis for fMRI data. In a cued-detection categorization task, participants detected whether an image from one of two target visual categories was present in a display. Our results revealed that categorical discrimination is modulated by behavioral relevance, as measured by the distributed pattern of response across the MD network. Distinctions between categories with different behavioral status (e.g., a target and a nontarget) were significantly discriminated. Category distinctions that were not behaviorally relevant (e.g., between two targets) were not discriminated. Other aspects of the task that were orthogonal to the behavioral decision did not modulate categorical discrimination. In a high visual region, the lateral occipital complex, modulation by behavioral relevance was evident in its posterior subregion but not in the anterior subregion. The results are consistent with the view of the MD system as involved in top-down attentional and cognitive control by selective coding of task-relevant discriminations. Significance statement: Control of cognitive demands fundamentally involves flexible allocation of attentional resources depending on a current behavioral context. Essential to such a mechanism is the ability to select currently relevant information and at the same time filter out information that is irrelevant. In an fMRI study, we measured distributed patterns of activity for objects from different visual categories while manipulating the behavioral relevance of the categorical distinctions. In a network of frontal and parietal cortical regions, the multiple-demand (MD) network, patterns reflected category distinctions that were relevant to behavior. Patterns could not be used to make task-irrelevant category distinctions. These findings demonstrate the ability of the MD network to implement complex goal-directed behavior by focused attention. PMID- 26354909 TI - Zeta Inhibitory Peptide, a Candidate Inhibitor of Protein Kinase Mzeta, Is Excitotoxic to Cultured Hippocampal Neurons. AB - The zeta-inhibitory peptide (ZIP) is considered a candidate inhibitor of the atypical protein kinase Mzeta (PKMzeta). ZIP has been shown to reverse established LTP and disrupt several forms of long-term memory. However, recent studies have challenged the specificity of ZIP, as it was reported to exert its effect also in PKMzeta knock-out mice. These results raise the question of what are the targets of ZIP that may underlie its effect on LTP and memory. Here we report that ZIP as well as its inactive analog, scrambled ZIP, induced a dose dependent increase in spontaneous activity of neurons in dissociated cultures of rat hippocampus. This was followed by a sustained elevation of intracellular calcium concentration ([Ca(2+)]i) which could not be blocked by conventional channel blockers. Furthermore, ZIP caused an increase in frequency of mEPSCs followed by an increase in membrane noise in patch-clamped neurons both in culture and in acute brain slices. Finally, at 5-10 MUM, ZIP-induced excitotoxic death of the cultured neurons. Together, our results suggest that the potential contribution of cellular toxicity should be taken into account in interpretation of ZIP's effects on neuronal and behavioral plasticity. Significance statement: The zeta-inhibitory peptide (ZIP) is considered a candidate inhibitor of the atypical protein kinase Mzeta (PKMzeta). ZIP has been shown to reverse established LTP and disrupt several forms of long-term memory. Here we report that ZIP as well as its inactive analog, scrambled ZIP, induced a dose-dependent increase in spontaneous activity of neurons in dissociated cultures and brain slices of rat hippocampus. Furthermore, ZIP caused a dose- and time-dependent neuronal death in the dissociated cultures. These findings impact on the assumption that ZIP erases memory due to specific inhibition of PKMz. PMID- 26354908 TI - Infralimbic EphB2 Modulates Fear Extinction in Adolescent Rats. AB - Adolescent rats are prone to impaired fear extinction, suggesting that mechanistic differences in extinction could exist in adolescent and adult rats. Since the infralimbic cortex (IL) is critical for fear extinction, we used PCR array technology to identify gene expression changes in IL induced by fear extinction in adolescent rats. Interestingly, the ephrin type B receptor 2 (EphB2), a tyrosine kinase receptor associated with synaptic development, was downregulated in IL after fear extinction. Consistent with the PCR array results, EphB2 levels of mRNA and protein were reduced in IL after fear extinction compared with fear conditioning, suggesting that EphB2 signaling in IL regulates fear extinction memory in adolescents. Finally, reducing EphB2 synthesis in IL with shRNA accelerated fear extinction learning in adolescent rats, but not in adult rats. These findings identify EphB2 in IL as a key regulator of fear extinction during adolescence, perhaps due to the increase in synaptic remodeling occurring during this developmental phase. PMID- 26354910 TI - Temporal Processing Capacity in High-Level Visual Cortex Is Domain Specific. AB - Prevailing hierarchical models propose that temporal processing capacity--the amount of information that a brain region processes in a unit time--decreases at higher stages in the ventral stream regardless of domain. However, it is unknown if temporal processing capacities are domain general or domain specific in human high-level visual cortex. Using a novel fMRI paradigm, we measured temporal capacities of functional regions in high-level visual cortex. Contrary to hierarchical models, our data reveal domain-specific processing capacities as follows: (1) regions processing information from different domains have differential temporal capacities within each stage of the visual hierarchy and (2) domain-specific regions display the same temporal capacity regardless of their position in the processing hierarchy. In general, character-selective regions have the lowest capacity, face- and place-selective regions have an intermediate capacity, and body-selective regions have the highest capacity. Notably, domain-specific temporal processing capacities are not apparent in V1 and have perceptual implications. Behavioral testing revealed that the encoding capacity of body images is higher than that of characters, faces, and places, and there is a correspondence between peak encoding rates and cortical capacities for characters and bodies. The present evidence supports a model in which the natural statistics of temporal information in the visual world may affect domain-specific temporal processing and encoding capacities. These findings suggest that the functional organization of high-level visual cortex may be constrained by temporal characteristics of stimuli in the natural world, and this temporal capacity is a characteristic of domain-specific networks in high-level visual cortex. Significance statement: Visual stimuli bombard us at different rates every day. For example, words and scenes are typically stationary and vary at slow rates. In contrast, bodies are dynamic and typically change at faster rates. Using a novel fMRI paradigm, we measured temporal processing capacities of functional regions in human high-level visual cortex. Contrary to prevailing theories, we find that different regions have different processing capacities, which have behavioral implications. In general, character-selective regions have the lowest capacity, face- and place-selective regions have an intermediate capacity, and body-selective regions have the highest capacity. These results suggest that temporal processing capacity is a characteristic of domain-specific networks in high-level visual cortex and contributes to the segregation of cortical regions. PMID- 26354911 TI - Neurotrophin-3 Enhances the Synaptic Organizing Function of TrkC-Protein Tyrosine Phosphatase sigma in Rat Hippocampal Neurons. AB - Neurotrophin-3 (NT-3) and its high-affinity receptor TrkC play crucial trophic roles in neuronal differentiation, axon outgrowth, and synapse development and plasticity in the nervous system. We demonstrated previously that postsynaptic TrkC functions as a glutamatergic synapse-inducing (synaptogenic) cell adhesion molecule trans-interacting with presynaptic protein tyrosine phosphatase sigma (PTPsigma). Given that NT-3 and PTPsigma bind distinct domains of the TrkC extracellular region, here we tested the hypothesis that NT-3 modulates TrkC/PTPsigma binding and synaptogenic activity. NT-3 enhanced PTPsigma binding to cell surface-expressed TrkC and facilitated the presynapse-inducing activity of TrkC in rat hippocampal neurons. Imaging of recycling presynaptic vesicles combined with TrkC knockdown and rescue approaches demonstrated that NT-3 rapidly potentiates presynaptic function via binding endogenous postsynaptic TrkC in a tyrosine kinase-independent manner. Thus, NT-3 positively modulates the TrkC PTPsigma complex for glutamatergic presynaptic assembly and function independently from TrkC kinase activation. Our findings provide new insight into synaptic roles of neurotrophin signaling and mechanisms controlling synaptic organizing complexes. Significance statement: Although many synaptogenic adhesion complexes have been identified in recent years, little is known about modulatory mechanisms. Here, we demonstrate a novel role of neurotrophin-3 in synaptic assembly and function as a positive modulator of the TrkC-protein tyrosine phosphatase sigma complex. This study provides new insight into the involvement of neurotrophin signaling in synapse development and plasticity, presenting a molecular mechanism that may underlie previous observations of short- and long term enhancement of presynaptic function by neurotrophin. Given the links of synaptogenic adhesion molecules to autism and schizophrenia, this study might also contribute to a better understanding of the pathogenesis of these disorders and provide a new direction for ameliorating imbalances in synaptic signaling networks. PMID- 26354912 TI - Neuronal Heterotopias Affect the Activities of Distant Brain Areas and Lead to Behavioral Deficits. AB - Neuronal heterotopia refers to brain malformations resulting from deficits of neuronal migration. Individuals with heterotopias show a high incidence of neurological deficits, such as epilepsy. More recently, it has come to be recognized that focal heterotopias may also show a range of psychiatric problems, including cognitive and behavioral impairments. However, because focal heterotopias are not always located in the brain areas responsible for the symptoms, the causal relationship between the symptoms and heterotopias remains elusive. In this study, we showed that mice with focal heterotopias in the somatosensory cortex generated by in utero electroporation exhibited spatial working memory deficit and low competitive dominance behavior, which have been shown to be closely associated with the activity of the medial prefrontal cortex (mPFC) in rodents. Analysis of the mPFC activity revealed that the immediate early gene expression was decreased and the local field potentials of the mPFC were altered in the mice with heterotopias compared with the control mice. Moreover, activation of these ectopic and overlying sister neurons using the DREADD (designer receptor exclusively activated by designer drug) system improved the working memory deficits. These findings suggest that cortical regions containing focal heterotopias can affect distant brain regions and give rise to behavioral abnormalities. Significance statement: Recent studies reported that patients with heterotopias have a variety of clinical symptoms, such as cognitive disturbance, psychiatric symptoms, and autistic behavior. However, the causal relationship between the symptoms and heterotopias remains elusive. Here we showed that mice with focal heterotopias in the somatosensory cortex generated by in utero electroporation exhibited behavioral deficits that have been shown to be associated with the mPFC activity in rodents. The existence of heterotopias indeed altered the neural activities of the mPFC, and direct manipulation of the neural activity of the ectopic neurons and their sister neurons in the overlying cortex improved the behavioral deficit. Thus, our results indicate that focal heterotopias could affect the activities of distant brain areas and cause behavioral abnormalities. PMID- 26354914 TI - Apparent and Actual Trajectory Control Depend on the Behavioral Context in Upper Limb Motor Tasks. AB - A central problem in motor neuroscience is to understand how we select, plan, and control motor actions. An influential idea is that the motor system computes and implements a desired limb trajectory, an intermediary control process between the behavioral goal (reach a spatial goal) and motor commands to move the limb. The most compelling evidence for trajectory control is that corrective responses are directed back toward the unperturbed trajectory when the limb is disturbed during movement. However, the idea of trajectory control conflicts with optimal control theories that emphasize goal-directed motor corrections. Here we show that corrective responses in human subjects can deviate back toward the unperturbed trajectory, but these reversals were only present when there were explicit limits on movement time. Our second experiment asked whether trajectory control could be generated if the trajectory was made an explicit goal of the task. Participants countered unexpected loads while reaching to a static goal, tracking a moving target, or maintaining their hand within a visually constrained path to a static goal. Corrective responses were directed back toward the constrained path or to intercept the moving target. However, corrections back to the unperturbed path disappeared when reaching to the static target. Long-latency muscle responses paralleled changes in the behavioral goal in both sets of experiments, but goal directed responses were delayed by 15-25 ms when tracking the moving goal. Our results show the motor system can behave like a trajectory controller but only if a "desired trajectory" is the goal of the task. Significance statement: One of the most influential ideas in motor control is that the motor system computes a "desired trajectory" when reaching to a spatial goal. Here we revisit the experimental paradigm from seminal papers supporting trajectory control to illustrate that corrective responses appear to return to the original trajectory of the limb, but only if there is an imposed timing constraint. We then provide direct evidence that the human motor system can behave like a trajectory controller, and return the limb to its original trajectory when a specified trajectory is the goal of the task. Our results show that the motor system is capable of a spectrum of corrective responses that depend on the behavioral goal of the motor task. PMID- 26354913 TI - In Vivo Inhibition of miR-155 Promotes Recovery after Experimental Mouse Stroke. AB - A multifunctional microRNA, miR-155, has been recently recognized as an important modulator of numerous biological processes. In our previous in vitro studies, miR 155 was identified as a potential regulator of the endothelial morphogenesis. The present study demonstrates that in vivo inhibition of miR-155 supports cerebral vasculature after experimental stroke. Intravenous injections of a specific miR 155 inhibitor were initiated at 48 h after mouse distal middle cerebral artery occlusion (dMCAO). Microvasculature in peri-infarct area, infarct size, and animal functional recovery were assessed at 1, 2, and 3 weeks after dMCAO. Using in vivo two-photon microscopy, we detected improved blood flow and microvascular integrity in the peri-infarct area of miR-155 inhibitor-injected mice. Electron microscopy revealed that, in contrast to the control group, these animals demonstrated well preserved capillary tight junctions (TJs). Western blot analysis data indicate that improved TJ integrity in the inhibitor-injected animals could be associated with stabilization of the TJ protein ZO-1 and mediated by the miR-155 target protein Rheb. MRI analysis showed significant (34%) reduction of infarct size in miR-155 inhibitor-injected animals at 21 d after dMCAO. Reduced brain injury was confirmed by electron microscopy demonstrating decreased neuronal damage in the peri-infarct area of stroke. Preservation of brain tissue was reflected in efficient functional recovery of inhibitor-injected animals. Based on our findings, we propose that in vivo miR 155 inhibition after ischemia supports brain microvasculature, reduces brain tissue damage, and improves the animal functional recovery. Significance statement: In the present study, we investigated an effect of the in vivo inhibition of a microRNA, miR-155, on brain recovery after experimental cerebral ischemia. To our knowledge, this is the first report describing the efficiency of intravenous anti-miRNA injections in a mouse model of ischemic stroke. The role of miRNAs in poststroke revascularization has been unexplored and in vivo regulation of miRNAs during the subacute phase of stroke has not yet been proposed. Our investigation introduces a new and unexplored approach to cerebral regeneration: regulation of poststroke angiogenesis and recovery through direct modulation of specific miRNA activity. We expect that our findings will lead to the development of novel strategies for regulating neurorestorative processes in the postischemic brain. PMID- 26354915 TI - Traveling Theta Waves in the Human Hippocampus. AB - The hippocampal theta oscillation is strongly correlated with behaviors such as memory and spatial navigation, but we do not understand its specific functional role. One hint of theta's function came from the discovery in rodents that theta oscillations are traveling waves that allow parts of the hippocampus to simultaneously exhibit separate oscillatory phases. Because hippocampal theta oscillations in humans have different properties compared with rodents, we examined these signals directly using multielectrode recordings from neurosurgical patients. Our findings confirm that human hippocampal theta oscillations are traveling waves, but also show that these oscillations appear at a broader range of frequencies compared with rodents. Human traveling waves showed a distinctive pattern of spatial propagation such that there is a consistent phase spread across the hippocampus regardless of the oscillations' frequency. This suggests that traveling theta oscillations are important functionally in humans because they coordinate phase coding throughout the hippocampus in a consistent manner. Significance statement: We show for the first time in humans that hippocampal theta oscillations are traveling waves, moving along the length of the hippocampus in a posterior-anterior direction. The existence of these traveling theta waves is important for understanding hippocampal neural coding because they cause neurons at separate positions in the hippocampus to experience different theta phases simultaneously. The theta phase that a neuron measures is a key factor in how that cell represents behavioral information. Therefore, the existence of traveling theta waves indicates that, to fully understand how a hippocampal neuron represents information, it is vital to also account for that cell's location in addition to conventional measures of neural activity. PMID- 26354916 TI - The Critical Role of Proteolytic Relay through Cathepsins B and E in the Phenotypic Change of Microglia/Macrophage. AB - Proteinase cascades are part of the basic machinery of neuronal death pathways. Neuronal cathepsin B (CatB), a typical cysteine lysosomal protease, plays a critical role in neuronal death through lysosomal leakage or excessive autophagy. On the other hand, much attention has been paid to microglial CatB in neuronal death. We herein show the critical role of proteolytic relay through microglial CatB and CatE in the polarization of microglia/macrophages in the neurotoxic phenotype, leading to hypoxia/ischemia (HI)-induced hippocampal neuronal damage in neonatal mice. HI caused extensive brain injury in neonatal wild-type mice, but not in CatB(-/-) mice. Furthermore, HI-induced polarization of microglia/macrophages in the neurotoxic phenotype followed by the neuroprotective phenotype in wild-type mice. On the other hand, microglia/macrophages exhibited only the early and transient polarization in the neuroprotective phenotype in CatB(-/-) mice. CA-074Me, a specific CatB inhibitor, significantly inhibited the neuronal death of primary cultured hippocampal neurons induced by the conditioned medium from cultured microglia polarized in the neurotoxic phenotype. Furthermore, CA-074Me prevented the activation of nuclear factor-kappaB (NF kappaB) in cultured microglia by inhibiting autophagic inhibitor of kappaBalpha degradation following exposure to oxygen-glucose deprivation. Rather surprisingly, CatE increased the CatB expression after HI by the liberation of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) from microglia through the proteasomal pathway. A significant increase in CatB and CatE levels was found exclusively in microglia/macrophages after HI. Thus, a proteolytic relay through the early CatE/TRAIL-dependent proteosomal and late CatB-dependent autophagic pathways for NF-kappaB activation may play a critical role in the polarization of microglia/macrophages in the neurotoxic phenotype. Significance statement: Proteinase cascades are part of the basic machinery of neuronal death pathways. Cathepsin B, a typical cysteine lysosomal protease, plays a critical role in neuronal death through lysosomal leakage or excessive autophagy in neurons. On the other hand, much attention has been also paid to the role of microglial cathepsin B in neuronal death. In this study, using in vivo and in vitro models of relevance to brain ischemia, we found a critical role of proteolytic relay through cathepsin B and cathepsin E in the neurotoxic polarization of microglia/macrophages, which is responsible for aggravation of hypoxia/ischemia-induced neuronal injury. These findings suggest orally active selective inhibitors of cathepsin B or cathepsin E as promising pharmacological agents for the treatment of ischemic brain injury. PMID- 26354918 TI - RORalpha Regulates Multiple Aspects of Dendrite Development in Cerebellar Purkinje Cells In Vivo. AB - The establishment of cell-type-specific dendritic arbors is fundamental for proper neural circuit formation. Here, using temporal- and cell-specific knock down, knock-out, and overexpression approaches, we show that multiple aspects of the dendritic organization of cerebellar Purkinje cells (PCs) are controlled by a single transcriptional factor, retinoic acid-related orphan receptor-alpha (RORalpha), a gene defective in staggerer mutant mice. As reported earlier, RORalpha was required for regression of primitive dendrites before postnatal day 4 (P4). RORalpha was also necessary for PCs to form a single Purkinje layer from P0 to P4. The knock-down of RORalpha from P4 impaired the elimination of perisomatic dendrites and maturation of single stem dendrites in PCs at P8. Filopodia and spines were also absent in these PCs. The knock-down of RORalpha from P8 impaired the formation and maintenance of terminal dendritic branches of PCs at P14. Finally, even after dendrite formation was completed at P21, RORalpha was required for PCs to maintain dendritic complexity and functional synapses, but their mature innervation pattern by single climbing fibers was unaffected. Interestingly, overexpression of RORalpha in PCs at various developmental stages did not facilitate dendrite development, but had specific detrimental effects on PCs. Because RORalpha deficiency during development is closely related to the severity of spinocerebellar ataxia type 1, delineating the specific roles of RORalpha in PCs in vivo at different time windows during development and throughout adulthood would facilitate our understanding of the pathogenesis of cerebellar disorders. Significance statement: The genetic programs by which each neuron subtype develops and maintains dendritic arbors have remained largely unclear. This is partly because dendrite development is modulated dynamically by neuronal activities and interactions with local environmental cues in vivo. In addition, dendrites are formed and maintained by the balance between their growth and regression; the effects caused by the disruption of transcription factors during the early developmental stages could be masked by dendritic growth or regression in the later stages. Here, using temporal- and cell-specific knock down, knock-out, and overexpression approaches in vivo, we show that multiple aspects of the dendritic organization of cerebellar Purkinje cells are controlled by a single transcriptional factor, retinoic acid-related orphan receptor alpha. PMID- 26354919 TI - Predicting the Dynamics of Network Connectivity in the Neocortex. AB - Dynamic remodeling of connectivity is a fundamental feature of neocortical circuits. Unraveling the principles underlying these dynamics is essential for the understanding of how neuronal circuits give rise to computations. Moreover, as complete descriptions of the wiring diagram in cortical tissues are becoming available, deciphering the dynamic elements in these diagrams is crucial for relating them to cortical function. Here, we used chronic in vivo two-photon imaging to longitudinally follow a few thousand dendritic spines in the mouse auditory cortex to study the determinants of these spines' lifetimes. We applied nonlinear regression to quantify the independent contribution of spine age and several morphological parameters to the prediction of the future survival of a spine. We show that spine age, size, and geometry are parameters that can provide independent contributions to the prediction of the longevity of a synaptic connection. In addition, we use this framework to emulate a serial sectioning electron microscopy experiment and demonstrate how incorporation of morphological information of dendritic spines from a single time-point allows estimation of future connectivity states. The distinction between predictable and nonpredictable connectivity changes may be used in the future to identify the specific adaptations of neuronal circuits to environmental changes. The full dataset is publicly available for further analysis. Significance statement: The neural architecture in the neocortex exhibits constant remodeling. The functional consequences of these modifications are poorly understood, in particular because the determinants of these changes are largely unknown. Here, we aimed to identify those modifications that are predictable from current network state. To that goal, we repeatedly imaged thousands of dendritic spines in the auditory cortex of mice to assess the morphology and lifetimes of synaptic connections. We developed models based on morphological features of dendritic spines that allow predicting future turnover of synaptic connections. The dynamic models presented in this paper provide a quantitative framework for adding putative temporal dynamics to the static description of a neuronal circuit from single time-point connectomics experiments. PMID- 26354917 TI - Repeated Mu-Opioid Exposure Induces a Novel Form of the Hyperalgesic Priming Model for Transition to Chronic Pain. AB - The primary afferent nociceptor was used as a model system to study mechanisms of pain induced by chronic opioid administration. Repeated intradermal injection of the selective mu-opioid receptor (MOR) agonist DAMGO induced mechanical hyperalgesia and marked prolongation of prostaglandin E2 (PGE2) hyperalgesia, a key feature of hyperalgesic priming. However, in contrast to prior studies of priming induced by receptor-mediated (i.e., TNFalpha, NGF, or IL-6 receptor) or direct activation of protein kinase Cepsilon (PKCepsilon), the pronociceptive effects of PGE2 in DAMGO-treated rats demonstrated the following: (1) rapid induction (4 h compared with 3 d); (2) protein kinase A (PKA), rather than PKCepsilon, dependence; (3) prolongation of hyperalgesia induced by an activator of PKA, 8-bromo cAMP; (4) failure to be reversed by a protein translation inhibitor; (5) priming in females as well as in males; and (6) lack of dependence on the isolectin B4-positive nociceptor. These studies demonstrate a novel form of hyperalgesic priming induced by repeated administration of an agonist at the Gi-protein-coupled MOR to the peripheral terminal of the nociceptor. Significance statement: The current study demonstrates the molecular mechanisms involved in the sensitization of nociceptors produced by repeated activation of mu-opioid receptors and contributes to our understanding of the painful condition observed in patients submitted to chronic use of opioids. PMID- 26354920 TI - How Visual Is the Visual Cortex? Comparing Connectional and Functional Fingerprints between Congenitally Blind and Sighted Individuals. AB - Classical animal visual deprivation studies and human neuroimaging studies have shown that visual experience plays a critical role in shaping the functionality and connectivity of the visual cortex. Interestingly, recent studies have additionally reported circumscribed regions in the visual cortex in which functional selectivity was remarkably similar in individuals with and without visual experience. Here, by directly comparing resting-state and task-based fMRI data in congenitally blind and sighted human subjects, we obtained large-scale continuous maps of the degree to which connectional and functional "fingerprints" of ventral visual cortex depend on visual experience. We found a close agreement between connectional and functional maps, pointing to a strong interdependence of connectivity and function. Visual experience (or the absence thereof) had a pronounced effect on the resting-state connectivity and functional response profile of occipital cortex and the posterior lateral fusiform gyrus. By contrast, connectional and functional fingerprints in the anterior medial and posterior lateral parts of the ventral visual cortex were statistically indistinguishable between blind and sighted individuals. These results provide a large-scale mapping of the influence of visual experience on the development of both functional and connectivity properties of visual cortex, which serves as a basis for the formulation of new hypotheses regarding the functionality and plasticity of specific subregions. Significance statement: How is the functionality and connectivity of the visual cortex shaped by visual experience? By directly comparing resting-state and task-based fMRI data in congenitally blind and sighted subjects, we obtained large-scale continuous maps of the degree to which connectional and functional "fingerprints" of ventral visual cortex depend on visual experience. In addition to revealing regions that are strongly dependent on visual experience (early visual cortex and posterior fusiform gyrus), our results showed regions in which connectional and functional patterns are highly similar in blind and sighted individuals (anterior medial and posterior lateral ventral occipital temporal cortex). These results serve as a basis for the formulation of new hypotheses regarding the functionality and plasticity of specific subregions of the visual cortex. PMID- 26354921 TI - Specific Early and Late Oddball-Evoked Responses in Excitatory and Inhibitory Neurons of Mouse Auditory Cortex. AB - A major challenge for sensory processing in the brain is considering stimulus context, such as stimulus probability, which may be relevant for survival. Excitatory neurons in auditory cortex, for example, adapt to repetitive tones in a stimulus-specific manner without fully generalizing to a low-probability deviant tone ("oddball") that breaks the preceding regularity. Whether such stimulus-specific adaptation (SSA) also prevails in inhibitory neurons and how it might relate to deviance detection remains elusive. We obtained whole-cell recordings from excitatory neurons and somatostatin- and parvalbumin-positive GABAergic interneurons in layer 2/3 of mouse auditory cortex and measured tone evoked membrane potential responses. All cell types displayed SSA of fast ("early") subthreshold and suprathreshold responses with oddball tones of a deviant frequency eliciting enlarged responses compared with adapted standards. SSA was especially strong when oddball frequency matched neuronal preference. In addition, we identified a slower "late" response component (200-400 ms after tone onset), most clearly in excitatory and parvalbumin-positive neurons, which also displayed SSA. For excitatory neurons, this late component reflected genuine deviance detection. Moreover, intracellular blockade of NMDA receptors reduced early and late responses in excitatory but not parvalbumin-positive neurons. The late component in excitatory neurons thus shares time course, deviance detection, and pharmacological features with the deviant-evoked event-related potential known as mismatch negativity (MMN) and provides a potential link between neuronal SSA and MMN. In summary, our results suggest a two-phase cortical activation upon oddball stimulation, with oddball tones first reactivating the adapted auditory cortex circuitry and subsequently triggering delayed reverberating network activity. Significance statement: Understanding how the brain encodes sensory context in addition to stimulus feature has been a main focus in neuroscience. Using in vivo targeted whole-cell recordings from excitatory and inhibitory neurons of mouse primary auditory cortex, we report two temporally distinct components of membrane potential responses encoding oddball tones that break stimulus regularity. Both components display stimulus-specific adaptation upon oddball paradigm stimulation in the three recorded cell types. The late response component, in particular, carries signatures of genuine deviance detection. In excitatory but not parvalbumin-positive inhibitory neurons, both early and late components depend on NMDA receptor-signaling. Our work proposes a potential neuronal substrate of a known deviant-evoked event-related potential, which is of fundamental significance in basic and clinical neuroscience. PMID- 26354922 TI - Remediation of Childhood Math Anxiety and Associated Neural Circuits through Cognitive Tutoring. AB - Math anxiety is a negative emotional reaction that is characterized by feelings of stress and anxiety in situations involving mathematical problem solving. High math-anxious individuals tend to avoid situations involving mathematics and are less likely to pursue science, technology, engineering, and math-related careers than those with low math anxiety. Math anxiety during childhood, in particular, has adverse long-term consequences for academic and professional success. Identifying cognitive interventions and brain mechanisms by which math anxiety can be ameliorated in children is therefore critical. Here we investigate whether an intensive 8 week one-to-one cognitive tutoring program designed to improve mathematical skills reduces childhood math anxiety, and we identify the neurobiological mechanisms by which math anxiety can be reduced in affected children. Forty-six children in grade 3, a critical early-onset period for math anxiety, participated in the cognitive tutoring program. High math-anxious children showed a significant reduction in math anxiety after tutoring. Remarkably, tutoring remediated aberrant functional responses and connectivity in emotion-related circuits anchored in the basolateral amygdala. Crucially, children with greater tutoring-induced decreases in amygdala reactivity had larger reductions in math anxiety. Our study demonstrates that sustained exposure to mathematical stimuli can reduce math anxiety and highlights the key role of the amygdala in this process. Our findings are consistent with models of exposure based therapy for anxiety disorders and have the potential to inform the early treatment of a disability that, if left untreated in childhood, can lead to significant lifelong educational and socioeconomic consequences in affected individuals. Significance statement: Math anxiety during early childhood has adverse long-term consequences for academic and professional success. It is therefore important to identify ways to alleviate math anxiety in young children. Surprisingly, there have been no studies of cognitive interventions and the underlying neurobiological mechanisms by which math anxiety can be ameliorated in young children. Here, we demonstrate that intensive 8 week one-to-one cognitive tutoring not only reduces math anxiety but also remarkably remediates aberrant functional responses and connectivity in emotion-related circuits anchored in the amygdala. Our findings are likely to propel new ways of thinking about early treatment of a disability that has significant implications for improving each individual's academic and professional chances of success in today's technological society that increasingly demands strong quantitative skills. PMID- 26354923 TI - An Obesity-Predisposing Variant of the FTO Gene Regulates D2R-Dependent Reward Learning. AB - Variations in the fat mass and obesity-associated (FTO) gene are linked to obesity. However, the underlying neurobiological mechanisms by which these genetic variants influence obesity, behavior, and brain are unknown. Given that Fto regulates D2/3R signaling in mice, we tested in humans whether variants in FTO would interact with a variant in the ANKK1 gene, which alters D2R signaling and is also associated with obesity. In a behavioral and fMRI study, we demonstrate that gene variants of FTO affect dopamine (D2)-dependent midbrain brain responses to reward learning and behavioral responses associated with learning from negative outcome in humans. Furthermore, dynamic causal modeling confirmed that FTO variants modulate the connectivity in a basic reward circuit of meso-striato-prefrontal regions, suggesting a mechanism by which genetic predisposition alters reward processing not only in obesity, but also in other disorders with altered D2R-dependent impulse control, such as addiction. Significance statement: Variations in the fat mass and obesity-associated (FTO) gene are associated with obesity. Here we demonstrate that variants of FTO affect dopamine-dependent midbrain brain responses and learning from negative outcomes in humans during a reward learning task. Furthermore, FTO variants modulate the connectivity in a basic reward circuit of meso-striato-prefrontal regions, suggesting a mechanism by which genetic vulnerability in reward processing can increase predisposition to obesity. PMID- 26354925 TI - Editorial: Controversies in Ocular Pharmacology. PMID- 26354924 TI - Emotional and Utilitarian Appraisals of Moral Dilemmas Are Encoded in Separate Areas and Integrated in Ventromedial Prefrontal Cortex. AB - Moral judgment often requires making difficult tradeoffs (e.g., is it appropriate to torture to save the lives of innocents at risk?). Previous research suggests that both emotional appraisals and more deliberative utilitarian appraisals influence such judgments and that these appraisals often conflict. However, it is unclear how these different types of appraisals are represented in the brain, or how they are integrated into an overall moral judgment. We addressed these questions using an fMRI paradigm in which human subjects provide separate emotional and utilitarian appraisals for different potential actions, and then make difficult moral judgments constructed from combinations of these actions. We found that anterior cingulate, insula, and superior temporal gyrus correlated with emotional appraisals, whereas temporoparietal junction and dorsomedial prefrontal cortex correlated with utilitarian appraisals. Overall moral value judgments were represented in an anterior portion of the ventromedial prefrontal cortex. Critically, the pattern of responses and functional interactions between these three sets of regions are consistent with a model in which emotional and utilitarian appraisals are computed independently and in parallel, and passed to the ventromedial prefrontal cortex where they are integrated into an overall moral value judgment. Significance statement: Popular accounts of moral judgment often describe it as a battle for control between two systems, one intuitive and emotional, the other rational and utilitarian, engaged in winner-take-all inhibitory competition. Using a novel fMRI paradigm, we identified distinct neural signatures of emotional and utilitarian appraisals and used them to test different models of how they compete for the control of moral behavior. Importantly, we find little support for competitive inhibition accounts. Instead, moral judgments resembled the architecture of simple economic choices: distinct regions represented emotional and utilitarian appraisals independently and passed this information to the ventromedial prefrontal cortex for integration into an overall moral value signal. PMID- 26354926 TI - Nanomaterial Based Approaches for the Diagnosis and Therapy of Cardiovascular Diseases. AB - The increasing prevalence and complexity of cardiovascular diseases demand innovative strategies for diagnostic and therapeutic applications to improve patient care/prognoses. Additionally, various factors constrain present cardiovascular therapies, including low aqueous drug solubility, early metabolism, short half-life and drug delivery limitations. The efficient treatment of cardiovascular diseases requires improvement of traditional drug delivery systems. This can be accomplished by using novel nanomaterial that can incorporate diverse bio-actives along with diagnostic agents in a single carrier, referred to as theranostics. This review discusses the state of the art in the applications to diagnosis and therapy of innovative, nanomaterial- based strategies such as lipid based carriers, nanocapsules, magnetic nanoparticles, gold nanoparticles, protein conjugated nanoparticles, dendrimers and carbon-based nanoformulations with a special emphasis on how they can contribute to improving the management of cardiovascular disease. PMID- 26354927 TI - Molecular classification of anaplastic oligodendroglioma using next-generation sequencing: a report of the prospective randomized EORTC Brain Tumor Group 26951 phase III trial. AB - BACKGROUND: Histopathological diagnosis of diffuse gliomas is subject to interobserver variation and correlates modestly with major prognostic and predictive molecular abnormalities. We investigated a series of patients with locally diagnosed anaplastic oligodendroglial tumors included in the EORTC phase III trial 26951 on procarbazine/lomustine/vincristine (PCV) chemotherapy to explore the diagnostic, prognostic, and predictive value of targeted next generation sequencing (NGS) in diffuse glioma and to assess the prognostic impact of FUBP1 and CIC mutations. METHODS: Mostly formalin-fixed paraffin-embedded samples were tested with targeted NGS for mutations in ATRX, TP53, IDH1, IDH2, CIC, FUBP1, PI3KC, TERT, EGFR, H3F3A, BRAF, PTEN, and NOTCH and for copy number alterations of chromosomes 1p, 19q, 10q, and 7. TERT mutations were also assessed, with PCR. RESULTS: Material was available from 139 cases, in 6 of which results were uninformative. One hundred twenty-six tumors could be classified: 20 as type II (IDH mutation [mut], "astrocytoma"), 49 as type I (1p/19q codeletion, "oligodendroglioma"), 55 as type III (7+/10q- or TERTmut and 1p/19q intact, "glioblastoma"), and 2 as childhood glioblastoma (H3F3Amut), leaving 7 unclassified (total 91% classified). Molecular classification was of clear prognostic significance and correlated better with outcome than did classical histopathology. In 1p/19q codeleted tumors, outcome was not affected by CIC and FUBP1 mutations. MGMT promoter methylation remained the most predictive factor for survival benefit of PCV chemotherapy. CONCLUSION: Targeted NGS allows a clinically relevant classification of diffuse glioma into groups with very different outcomes. The diagnosis of diffuse glioma should be primarily based on a molecular classification, with the histopathological grade added to it. Future discussion should primarily aim at establishing the minimum requirements for molecular classification of diffuse glioma. PMID- 26354928 TI - Nevospheres from neurocutaneous melanocytosis cells show reduced viability when treated with specific inhibitors of NRAS signaling pathway. AB - BACKGROUND: Neurocutaneous melanocytosis (NCM) is characterized by clonal nevomelanocytic proliferations in the CNS and skin. Given the scarcity of effective therapeutic targets, testing new drugs requires a reliable and reproducible in vitro cellular model of the disease. METHODS: We generated nevomelanocytic spheroids in vitro from lesions of the spinal cord, brain, and skin from 4 NCM patients. Nevomelanocytic cells were grown as monolayers or spheroids and their growth characteristics were evaluated. Cultured cell identity was confirmed by demonstration of the same NRAS mutation found in the original lesions and by immunophenotyping. Nevomelanocytic spheroids were treated with inhibitors of specific mediators of the NRAS signaling pathway (vemurafenib, MEK162, GDC0941, and GSK2126458). Drug sensitivity and cell viability were assessed. RESULTS: Cultured cells were growth-factor dependent, grew as spheroids on Geltrex matrix, and maintained their clonogenicity in vitro over passages. Skin-derived cells formed more colonies than CNS-derived cells. Inhibitors of specific mediators of the NRAS signaling pathway reduced viability of NRAS mutated cells. The highest effect was obtained with GSK2126458, showing a viability reduction below 50%. CONCLUSIONS: NRAS mutated cells derived from clinical NCM samples are capable of continuous growth as spheroid colonies in vitro and retain their genetic identity. Drugs targeting the NRAS signaling pathway reduce in vitro viability of NCM cells. NCM lesional spheroids represent a new and reliable experimental model of NCM for use in drug testing and mechanistic studies. PMID- 26354929 TI - Kinetics of tumor size and peritumoral brain edema before, during, and after systemic therapy in recurrent WHO grade II or III meningioma. AB - BACKGROUND: The efficacy of systemic antineoplastic therapy on recurrent World Health Organization (WHO) grades II and III meningiomas is unclear. METHODS: We performed a retrospective multicenter analysis of serial cranial MRI in patients with recurrent WHO II and III meningiomas treated with antineoplastic systemic therapies. Growth rates for tumor volume and diameter, as well as change rates for edema size, were calculated for all lesions. RESULTS: We identified a total of 34 patients (23 atypical, 11 anaplastic meningiomas) with a total of 57 meningioma lesions who had been treated at 6 European institutions. Systemic therapies included bevacizumab, cytotoxic chemotherapy, somatostatin analogues, and tyrosine kinase inhibitors. Overall, tumor growth rates decreased during systemic therapy by 51% for tumor diameter and 14% for tumor volume growth rates compared with the period before initiation of systemic therapy. The most pronounced decrease in meningioma growth rates during systemic therapy was evident in patients treated with bevacizumab, with a reduction of 80% in diameter and 59% in volume growth. Furthermore, a decrease in size of peritumoral edema after initiation of systemic therapy was exclusively observed in patients treated with bevacizumab (-107%). CONCLUSIONS: Our data indicate that systemic therapy may inhibit growth of recurrent WHO grades II and III meningiomas to some extent. In our small cohort, bevacizumab had the most pronounced inhibitory effect on tumor growth, as well as some anti-edematous activity. Prospective studies are needed to better define the role of medical therapies in this tumor type. PMID- 26354930 TI - HaloPlex Targeted Resequencing for Mutation Detection in Clinical Formalin-Fixed, Paraffin-Embedded Tumor Samples. AB - In recent years, the advent of massively parallel next-generation sequencing technologies has enabled substantial advances in the study of human diseases. Combined with targeted DNA enrichment methods, high sequence coverage can be obtained for different genes simultaneously at a reduced cost per sample, creating unique opportunities for clinical cancer diagnostics. However, the formalin-fixed, paraffin-embedded (FFPE) process of tissue samples, routinely used in pathology departments, results in DNA fragmentation and nucleotide modifications that introduce a number of technical challenges for downstream biomolecular analyses. We evaluated the HaloPlex target enrichment system for somatic mutation detection in 80 tissue fractions derived from 20 clinical cancer cases with paired tumor and normal tissue available in both FFPE and fresh-frozen format. Several modifications to the standard method were introduced, including a reduced target fragment length and two strand capturing. We found that FFPE material can be used for HaloPlex-based target enrichment and next-generation sequencing, even when starting from small amounts of DNA. By specifically capturing both strands for each target fragment, we were able to reduce the number of false-positive errors caused by FFPE-induced artifacts and lower the detection limit for somatic mutations. We believe that the HaloPlex method presented here will be broadly applicable as a tool for somatic mutation detection in clinical cancer settings. PMID- 26354931 TI - Embryos of a moss can be hardened to desiccation tolerance: effects of rate of drying on the timeline of recovery and dehardening in Aloina ambigua (Pottiaceae). AB - BACKGROUND AND AIMS: Embryonic sporophytes of the moss Aloina ambigua are inducibly desiccation tolerant (DT). Hardening to DT describes a condition of temporary tolerance to a rapid-drying event conferred by a previous slow-drying event. This paper aimed to determine whether sporophytic embryos of a moss can be hardened to DT, to assess how the rate of desiccation influences the post rehydration dynamics of recovery, hardening and dehardening, and to determine the minimum rate of drying for embryos and shoots. METHODS: Embryos were exposed to a range of drying rates using wetted filter paper in enclosed Petri dishes, monitoring relative humidity (RH) inside the dish and equilibrating tissues with 50% RH. Rehydrated embryos and shoots were subjected to a rapid-drying event at intervals, allowing assessments of recovery, hardening and dehardening times. KEY RESULTS: The minimum rate of slow drying for embryonic survival was ~3.5 h and for shoots ~9 h. Hardening to DT was dependent upon the prior rate of drying. When the rate of drying was extended to 22 h, embryonic hardening was strong (>50% survival) with survival directly proportional to the post-rehydration interval preceding rapid drying. The recovery time (repair/reassembly) was so short as to be undetectable in embryos and shoots desiccated gradually; however, embryos dried in <3.5 h exhibited a lag time in development of ~4 d, consistent with recovery. Dehardening resulted in embryos incapable of surviving a rapid drying event. CONCLUSIONS: The ability of moss embryos to harden to DT and the influence of prior rate of drying on the dynamics of hardening are shown for the first time. The minimum rate of drying is introduced as a new metric for assessing ecological DT, defined as the minimum duration at sub-turgor during a drying event in which upon rehydration the plant organ of interest survives relatively undamaged from the desiccating event. PMID- 26354932 TI - The Insect Chemoreceptor Superfamily Is Ancient in Animals. AB - The insect chemoreceptor superfamily consists of 2 gene families, the highly diverse gustatory receptors (GRs) found in all arthropods with sequenced genomes and the odorant receptors that evolved from a GR lineage and have been found only in insects to date. Here, I describe relatives of the insect chemoreceptor superfamily, specifically the basal GR family, in diverse other animals, showing that the superfamily dates back at least to early animal evolution. GR-Like (GRL) genes are present in the genomes of the placozoan Trichoplax adhaerens, an anemone Nematostella vectensis, a coral Acropora digitifera, a polychaete Capitella teleta, a leech Helobdella robusta, the nematode Caenorhabditis elegans (and many other nematodes), 3 molluscs (a limpet Lottia gigantea, an oyster Crassostrea gigas, and the sea hare Aplysia californica), the sea urchin Strongylocentrotus purpuratus, and the sea acorn Saccoglossus kowalevskii. While some of these animals contain multiple divergent GRL lineages, GRLs have been lost entirely from other animal lineages such as vertebrates. GRLs are absent from the ctenophore Mnemiopsis leidyi, the demosponge Amphimedon queenslandica, and 2 available chaonoflagellate genomes, so it remains unclear whether this superfamily originated before or during animal evolution. PMID- 26354933 TI - Chemosensory Dysfunction in Alcohol-Related Disorders: A Joint Exploration of Olfaction and Taste. AB - Chemosensory (olfaction-taste) dysfunctions are considered as reliable biomarkers in many neurological and psychiatric states. However, experimental measures of chemosensory abilities are lacking in alcohol-dependence (AD) and Korsakoff Syndrome (KS, a neurological complication of AD), despite the role played by alcohol-related odors and taste in the emergence and maintenance of AD. This study thus investigated chemosensory impairments in AD and KS. Olfactory gustatory measures were taken among 20 KS, 20 AD, and 20 control participants. Olfaction (odor detection-discrimination-identification) was assessed using the "Sniffin Sticks" battery and taste was measured using the "Taste Strips" task. Impairments were found for high-level olfaction in AD (odor discrimination) and KS (odor discrimination-identification), even after controlling for psychopathological comorbidities. Gustatory deficits were also observed in both groups, indexing a global deficit for chemosensory perception. Finally, the gradient of impairment between the successive disease stages for odor identification suggests that the hypothesis of a continuum between AD and KS regarding cognitive deficits can be generalized to chemosensory perception. AD and KS are thus characterized by deficits in chemosensory abilities, which could constitute a marker of the AD-KS transition. In view of its deleterious influence on everyday life, chemosensory dysfunction should also be taken into account in clinical settings. PMID- 26354934 TI - Ectodysplasin signalling genes and phenotypic evolution in sculpins (Cottus). AB - Despite their deeply conserved function among vertebrates, ectodysplasin (Eda) signalling genes are involved in microevolutionary change in humans and sticklebacks. If such a dual role is common, Eda signalling genes constitute hotspots for morphological evolution. Variation in sculpin (Cottus) skin prickling and body shape resembles patterns caused by variation in Eda signalling in sticklebacks. We mapped Eda signalling genes and performed quantitative trait locus mapping in crosses between Cottus rhenanus and Cottus perifretum. A genomic region containing the Eda receptor (Edar) was strongly associated with prickling and contributed to shape. The expression of Edar in developing prickles and skeletal elements in Cottus was confirmed by in situ hybridization. Coding sequence changes between Edar alleles in C. rhenanus and C. perifretum exceeded sequence differentiation in other vertebrates. However, it is likely that additional genetic elements besides coding changes affect the phenotypic variation. Although the phenotype in a natural hybrid lineage between C. rhenanus and C. perifretum resembles C. perifretum, the respective coding Edar alleles are not fully fixed (88.6%). Hence, our results support an involvement of Eda signalling in microevolutionary changes, but imply that the Edar gene is affected by multiple evolutionary processes that vary among freshwater sculpins. PMID- 26354935 TI - Exploring the nature of ecological specialization in a coral reef fish community: morphology, diet and foraging microhabitat use. AB - Patterns of ecological specialization offer invaluable information about ecosystems. Yet, specialization is rarely quantified across several ecological niche axes and variables beyond the link between morphological and dietary specialization have received little attention. Here, we provide a quantitative evaluation of ecological specialization in a coral reef fish assemblage (f. Acanthuridae) along one fundamental and two realized niche axes. Specifically, we examined ecological specialization in 10 surgeonfish species with regards to morphology and two realized niche axes associated with diet and foraging microhabitat utilization using a recently developed multidimensional framework. We then investigated the potential relationships between morphological and behavioural specialization. These relationships differed markedly from the traditional ecomorphological paradigm. While morphological specialization showed no relationship with dietary specialization, it exhibited a strong relationship with foraging microhabitat specialization. However, this relationship was inverted: species with specialized morphologies were microhabitat generalists, whereas generalized morphotypes were microhabitat specialists. Interestingly, this mirrors relationships found in plant-pollinator communities and may also be applicable to other ecosystems, highlighting the potential importance of including niche axes beyond dietary specialization into ecomorphological frameworks. On coral reefs, it appears that morphotypes commonly perceived as most generalized may, in fact, be specialized in exploiting flat and easily accessible microhabitats. PMID- 26354936 TI - Competition for resources can explain patterns of social and individual learning in nature. AB - In nature, animals often ignore socially available information despite the multiple theoretical benefits of social learning over individual trial-and-error learning. Using information filtered by others is quicker, more efficient and less risky than randomly sampling the environment. To explain the mix of social and individual learning used by animals in nature, most models penalize the quality of socially derived information as either out of date, of poor fidelity or costly to acquire. Competition for limited resources, a fundamental evolutionary force, provides a compelling, yet hitherto overlooked, explanation for the evolution of mixed-learning strategies. We present a novel model of social learning that incorporates competition and demonstrates that (i) social learning is favoured when competition is weak, but (ii) if competition is strong social learning is favoured only when resource quality is highly variable and there is low environmental turnover. The frequency of social learning in our model always evolves until it reduces the mean foraging success of the population. The results of our model are consistent with empirical studies showing that individuals rely less on social information where resources vary little in quality and where there is high within-patch competition. Our model provides a framework for understanding the evolution of social learning, a prerequisite for human cumulative culture. PMID- 26354937 TI - Admixture between native and invasive populations may increase invasiveness of Mimulus guttatus. AB - Self-fertilization and admixture of genotypes from different populations can have major fitness consequences in native species. However, few studies have addressed their potential roles in invasive species. Here, we used plants of Mimulus guttatus from seven native North American, three invasive Scottish and four invasive New Zealand populations to address this. We created seeds from self fertilization, within-population outcrossing, between-population outcrossing within the same range, and outcrossing between the native and invasive ranges. A greenhouse experiment showed that native and invasive plants of M. guttatus suffered to similar degrees from inbreeding depression, in terms of asexual reproduction and biomass production. After outcrossing with plants from other populations, M. guttatus benefited from heterosis, in terms of asexual and sexual reproduction, and biomass production, particularly when plants from native and invasive populations were crossed. This suggests that, when novel genotypes of M. guttatus from the native North American range will be introduced to the invasive ranges, subsequent outcrossing with M. guttatus plants that are already there might further boost invasiveness of this species. PMID- 26354938 TI - Genome size correlates with reproductive fitness in seed beetles. AB - The ultimate cause of genome size (GS) evolution in eukaryotes remains a major and unresolved puzzle in evolutionary biology. Large-scale comparative studies have failed to find consistent correlations between GS and organismal properties, resulting in the 'C-value paradox'. Current hypotheses for the evolution of GS are based either on the balance between mutational events and drift or on natural selection acting upon standing genetic variation in GS. It is, however, currently very difficult to evaluate the role of selection because within-species studies that relate variation in life-history traits to variation in GS are very rare. Here, we report phylogenetic comparative analyses of GS evolution in seed beetles at two distinct taxonomic scales, which combines replicated estimation of GS with experimental assays of life-history traits and reproductive fitness. GS showed rapid and bidirectional evolution across species, but did not show correlated evolution with any of several indices of the relative importance of genetic drift. Within a single species, GS varied by 4-5% across populations and showed positive correlated evolution with independent estimates of male and female reproductive fitness. Collectively, the phylogenetic pattern of GS diversification across and within species in conjunction with the pattern of correlated evolution between GS and fitness provide novel support for the tenet that natural selection plays a key role in shaping GS evolution. PMID- 26354939 TI - Long-term acclimation to elevated pCO2 alters carbon metabolism and reduces growth in the Antarctic diatom Nitzschia lecointei. AB - Increasing atmospheric CO2 levels are driving changes in the seawater carbonate system, resulting in higher pCO2 and reduced pH (ocean acidification). Many studies on marine organisms have focused on short-term physiological responses to increased pCO2, and few on slow-growing polar organisms with a relative low adaptation potential. In order to recognize the consequences of climate change in biological systems, acclimation and adaptation to new environments are crucial to address. In this study, physiological responses to long-term acclimation (194 days, approx. 60 asexual generations) of three pCO2 levels (280, 390 and 960 uatm) were investigated in the psychrophilic sea ice diatom Nitzschia lecointei. After 147 days, a small reduction in growth was detected at 960 uatm pCO2. Previous short-term experiments have failed to detect altered growth in N. lecointei at high pCO2, which illustrates the importance of experimental duration in studies of climate change. In addition, carbon metabolism was significantly affected by the long-term treatments, resulting in higher cellular release of dissolved organic carbon (DOC). In turn, the release of labile organic carbon stimulated bacterial productivity in this system. We conclude that long-term acclimation to ocean acidification is important for N. lecointei and that carbon overconsumption and DOC exudation may increase in a high-CO2 world. PMID- 26354941 TI - Hollow-fiber solvent bar microextraction with gas chromatography and electron capture detection determination of disinfection byproducts in water samples. AB - A liquid-phase microextraction method that uses a hollow-fiber solvent bar microextraction technique was developed by combining gas chromatography with electron capture detection for the analysis of four trihalomethanes (chloroform, dichlorobromomethane, chlorodibromomethane, and bromoform) in drinking water. In the microextraction process, 1-octanol was used as the solvent. The technique operates in a two-phase mode with a 5 min extraction time, a 700 rpm stirring speed, a 30 degrees C extraction temperature, and NaCl concentration of 20%. After microextraction, one edge of the membrane was cut, and 1 MUL of solvent was collected from the membrane using a 10 MUL syringe. The solvent sample was directly injected into the gas chromatograph. The analytical characteristics of the developed method were as follows: detection limits, 0.017-0.037 ng mL-1 ; linear working range, 10-900 ng mL-1 ; recovery, 74 +/- 9-91 +/- 2; relative standard deviation, 5.7-10.3; and enrichment factor, 330-455. A simple, fast, economic, selective, and efficient method with big possibilities for automation was developed with a potential use to apply with other matrices and analytes. PMID- 26354940 TI - No deep diving: evidence of predation on epipelagic fish for a stem beaked whale from the Late Miocene of Peru. AB - Although modern beaked whales (Ziphiidae) are known to be highly specialized toothed whales that predominantly feed at great depths upon benthic and benthopelagic prey, only limited palaeontological data document this major ecological shift. We report on a ziphiid-fish assemblage from the Late Miocene of Peru that we interpret as the first direct evidence of a predator-prey relationship between a ziphiid and epipelagic fish. Preserved in a dolomite concretion, a skeleton of the stem ziphiid Messapicetus gregarius was discovered together with numerous skeletons of a clupeiform fish closely related to the epipelagic extant Pacific sardine (Sardinops sagax). Based on the position of fish individuals along the head and chest regions of the ziphiid, the lack of digestion marks on fish remains and the homogeneous size of individuals, we propose that this assemblage results from the death of the whale (possibly via toxin poisoning) shortly after the capture of prey from a single school. Together with morphological data and the frequent discovery of fossil crown ziphiids in deep-sea deposits, this exceptional record supports the hypothesis that only more derived ziphiids were regular deep divers and that the extinction of epipelagic forms may coincide with the radiation of true dolphins. PMID- 26354942 TI - Sequence of electrode implantation and outcome of deep brain stimulation for Parkinson's disease. AB - INTRODUCTION: The effect of the variability of electrode placement on outcomes after bilateral deep brain stimulation of subthalamic nucleus has not been sufficiently studied, especially with respect to the sequence of hemisphere implantation. METHODOLOGY: We retrospectively analysed the clinical and radiographic data of all the consecutive patients with Parkinson's disease who underwent surgery at our centre and completed at least 1 year follow-up. The dispersion in electrode location was calculated by the square of deviation from population mean, and the direction of deviation was analysed by comparing the intended and final implantation coordinates. Linear regression analysis was performed to analyse the predictors of postoperative improvement of the motor condition, also controlling for the sequence of implanted hemisphere. RESULTS: 76 patients (mean age 58+/-7.2 years) were studied. Compared with the first side, the second side electrode tip had significantly higher dispersion as an overall effect (5.6+/-21.6 vs 2.2+/-4.9 mm(2), p=0.04), or along the X-axis (4.1+/-15.6 vs 1.4+/-2.4 mm(2), p=0.03) and Z-axis (4.9+/-11.5 vs 2.9+/-3.6 mm(2), p=0.02); the second side stimulation was also associated with a lower threshold for side effects (contact 0, p<0.001 and contact 3, p=0.004). In the linear regression analysis, the significant predictors of outcome were baseline activities of daily living (p=0.010) and dispersion of electrode on the second side (p=0.005). CONCLUSIONS: We observed a higher dispersion for the electrode on the second implanted side, which also resulted to be a significant predictor of motor outcome at 1 year. PMID- 26354943 TI - Vernet's syndrome induced by internal jugular vein thrombosis. PMID- 26354944 TI - Endovascular treatment of ophthalmic artery aneurysms: ophthalmic artery patency following flow diversion versus coil embolization. AB - BACKGROUND AND PURPOSE: The Pipeline Embolization Device (PED) has been shown to effectively treat complex internal carotid artery aneurysms while maintaining patency of covered side branches. The purpose of this retrospective matched cohort study is to evaluate the effect of flow diversion on the patency of the ophthalmic artery when treating ophthalmic artery aneurysms. METHODS: A retrospective review of our prospectively collected institutional database identified 19 ophthalmic artery aneurysms treated with a PED. These were matched according to aneurysm diameter in a 1:2 fashion to ophthalmic artery aneurysms treated via coil embolization, although it is important to note that there was a statistically significance difference in the neck diameter between the two groups (p=0.045). Clinical and angiographic outcomes were recorded and analyzed. RESULTS: On follow-up angiography, decreased flow through the ophthalmic artery was observed in 26% of the PED cohort and 0% of the coil embolization cohort (p=0.003). No ophthalmologic complications were noted in either cohort. Complete occlusion at 12 months was more common following PED treatment than coil embolization (74% vs 47%; p=0.089), although lower than reported in previous trials. This may be due to inflow into the ophthalmic artery keeping the aneurysm patent. Retreatments were more common following coil embolization than PED (24% vs 11%), but this was not significant (p=0.304). Permanent morbidity rates were not significantly different between the PED (11%) and coil embolization (3%) cohorts (p=0.255). CONCLUSIONS: Our results suggest that ophthalmic artery aneurysms may be adequately and safely treated with either the PED or coil embolization. However, treatment with the PED carries a higher risk of impeding flow to the ophthalmic artery, although this did not result in clinical sequelae in the current study. PMID- 26354945 TI - Intraprocedural abciximab bolus versus pretreatment oral dual antiplatelet medication for endovascular stenting of unruptured intracranial aneurysms. AB - BACKGROUND: Standard pretreatment with dual antiplatelet medication (DAPM) was compared with a standalone intraprocedural abciximab bolus for the prevention of thromboembolic and hemorrhagic events during endovascular stenting of unruptured intracranial aneurysms. MATERIALS AND METHODS: We treated 94 patients with 99 aneurysms with intracranial stenting (with or without coiling). Patients were either pretreated with DAPM daily for >=3 days before stenting (pretreatment group) or received an abciximab bolus during or immediately after stent placement followed by postoperative DAPM (abciximab group), at the treating physician's discretion. Twenty patients underwent immediate postoperative MRI. Demographic, clinical, and radiological information and periprocedural complications were recorded. RESULTS: There were 52 procedures in the pretreatment group and 47 in the abciximab group. More flow-diverting stents were placed in the pretreatment group than in the abciximab group (45 vs 23, p<0.001), and the aneurysm diameter was larger (11.2+/-6.7 vs 8.3+/-4.7 mm, p=0.01). There were 11 thrombotic and 7 access site complications, with no significant difference between the groups (p>0.99 and p=0.12, respectively). There were no intracranial hemorrhages. In patients with postoperative MRI, there was no difference in the presence of diffusion-restricted lesions between groups (p=0.20). Multivariate analysis of a composite of any complication did not show significant associations with aneurysm or patient variables in either group. CONCLUSIONS: Standalone intraprocedural abciximab bolus was not associated with an increased rate of complications compared with pretreatment with DAPM for unruptured intracranial aneurysm stenting. PMID- 26354946 TI - Simultaneous Determination of Cinnarizine and Dimenhydrinate in Binary Mixture Using Chromatographic Methods. AB - Two accurate and sensitive chromatographic methods have been developed and validated for simultaneous determination of cinnarizine (CIN) and dimenhydrinate (DIM). The first method uses simultaneous quantitative thin layer chromatography (TLC) spectrodensitometric evaluation of them, using ethyl acetate:methylene chloride (8 : 2 by volume) as a mobile phase. Chromatograms are scanned at 254 nm. This method analyzes CIN in a concentration range of 0.5-6 ug per band with mean percentage recovery of 99.78 +/- 1.001 and DIM in a concentration range of 1 6 ug per band with mean percentage recovery of 99.87 +/- 1.319. The second method is high-performance liquid chromatography using methanol:acetonitrile:water [85 : 10 : 5, by volume +0.5% tri ethyl amine (TEA)] as a mobile phase. The linearity was found to be in the range of 10-60 and 5-60 ug mL(-1) for CIN and DIM, respectively. The methods were successfully applied to the simultaneous determination of CIN and DIM in bulk powder, laboratory-prepared mixtures and pharmaceutical dosage forms. The validity of results was assessed by applying standard addition techniques. The results obtained are found to agree statistically with those obtained by a reported method, showing no significant difference with respect to accuracy and precision. PMID- 26354947 TI - HPLC-PDA Method for Simultaneous Determination of Nine Marker Components in Banhasasim-Tang. AB - A simple and accurate high-performance liquid chromatography-photodiode array (HPLC-PDA) detection method has been developed and validated for simultaneous determination of nine components-liquiritin, coptisine, baicalin, palmatine, berberine, wogonoside, baicalein, glycyrrhizin and wogonin-in the traditional Korean formula, Banhasasim-tang decoction. A Gemini C18 analytical column was used to separate the nine constituents and kept at 40 degrees C by gradient elution with 0.1% (v/v) trifluoroacetic acid in distilled water (A) and acetonitrile (B) as mobile phases. The flow rate was 1.0 mL/min and the injection volume was 10 uL. The PDA detection wavelengths were set at 254, 275 and 350 nm. Calibration curves of all compounds showed good linearity with coefficients of determination >=0.9998 within the test ranges. The limits of detection and quantification of all compounds were in the range 0.01-0.09 and 0.03-0.30 ug/mL, respectively. All recoveries of the nine marker compounds ranged from 98.65 to 103.22% with relative standard deviation (RSD) values <1.25%. The RSDs of intraday and interday precision were <1.13 and 1.83%, respectively. The concentrations of the nine marker constituents were 0.19-41.09 mg/g. PMID- 26354950 TI - Insights into the Impact of Heterogeneous Glycosylation on the Pharmacokinetic Behavior of Follistatin-Fc-Based Biotherapeutics. AB - Follistatin 315 heparan sulfate-binding deficient mutant human IgG4 Fc fusion (FST-DeltaHBS-Fc) is a follistatin (FST) based Fc fusion protein currently being developed as a novel therapy for several potential indications, including muscle wasting. Previous assessments of the pharmacokinetics and therapeutic activity of FST-DeltaHBS-Fc have shown a close association of the exposure-response relationship. The current work builds upon these initial studies by investigating the glycosylation characteristics of FST-DeltaHBS-Fc after recombinant expression and its impact on the pharmacokinetics in mice and Cynomolgus monkeys. The data presented indicate that FST-DeltaHBS-Fc is heterogeneously glycosylated at the three putative sites in FST when recombinantly expressed in stably transfected Chinese hamster ovary cells. Such carbohydrate heterogeneity, especially with regards to sialic acid incorporation, directly results in sugar-dependent clearance in both mice and Cynomolgus monkeys. Examination of the pharmacokinetics of FST-DeltaHBS-Fc molecules containing variable sialic acid content in asialoglycoprotein receptor 1 (ASPGR-1) knockout mice supports the receptor's role as part of the clearance mechanism of the molecules. Based on the evaluation of several variably sialylated lots of material in pharmacokinetic assessments, we define specifications for average sialic acid incorporation into FST-DeltaHBS-Fc that result in limited sugar-mediated clearance. Taken together, these studies highlight the importance of establishing an early understanding of the glycosylation/pharmacokinetic relationships of FST-DeltaHBS-Fc, which will provide a basis for future application toward optimal systemic drug delivery and dosing strategies. PMID- 26354948 TI - Modulation of P-glycoprotein at the Human Blood-Brain Barrier by Quinidine or Rifampin Treatment: A Positron Emission Tomography Imaging Study. AB - Permeability-glycoprotein (P-glycoprotein, P-gp), an efflux transporter at the human blood-brain barrier (BBB), is a significant obstacle to central nervous system (CNS) delivery of P-gp substrate drugs. Using positron emission tomography imaging, we investigated P-gp modulation at the human BBB by an approved P-gp inhibitor, quinidine, or the P-gp inducer, rifampin. Cerebral blood flow (CBF) and BBB P-gp activity were respectively measured by administration of (15)O-water followed by (11)C-verapamil. In a crossover design, healthy volunteers received quinidine and 11-29 days of rifampin treatment during different study periods. CBF and P-gp activity was measured in the absence (control; prior to quinidine treatment) and presence of P-gp modulation. At clinically relevant quinidine plasma concentrations, P-gp inhibition resulted in a 60% increase in (11)C radioactivity distribution across the human BBB as measured by the brain extraction ratio (ER) of (11)C-radioactivity. Furthermore, the magnitude of BBB P gp inhibition by quinidine was successfully predicted by a combination of in vitro and macaque data, but not by rat data. Although our findings demonstrated that quinidine did not completely inhibit P-gp at the human BBB, it has the potential to produce clinically significant CNS drug interactions with P-gp substrate drugs that exhibit a narrow therapeutic window and are significantly excluded from the brain by P-gp. Rifampin treatment induced systemic CYP3A metabolism of (11)C-verapamil; however, it reduced the ER by 6%. Therefore, we conclude that rifampin, at its usual clinical dose, cannot be used to induce P-gp at the human BBB to a clinically meaningful extent and is unlikely to cause inadvertent BBB-inductive drug interactions. PMID- 26354949 TI - Xenobiotic Metabolism in Mice Lacking the UDP-Glucuronosyltransferase 2 Family. AB - UDP-Glucuronosyltransferases (UGTs) conjugate a glucuronyl group from glucuronic acid to a wide range of lipophilic substrates to form a hydrophilic glucuronide conjugate. The glucuronide generally has decreased bioactivity and increased water solubility to facilitate excretion. Glucuronidation represents an important detoxification pathway for both endogenous waste products and xenobiotics, including drugs and harmful industrial chemicals. Two clinically significant families of UGT enzymes are present in mammals: UGT1s and UGT2s. Although the two families are distinct in gene structure, studies using recombinant enzymes have shown considerable overlap in their ability to glucuronidate many substrates, often obscuring the relative importance of the two families in the clearance of particular substrates in vivo. To address this limitation, we have generated a mouse line, termed DeltaUgt2, in which the entire Ugt2 gene family, extending over 609 kilobase pairs, is excised. This mouse line provides a means to determine the contributions of the two UGT families in vivo. We demonstrate the utility of these animals by defining for the first time the in vivo contributions of the UGT1 and UGT2 families to glucuronidation of the environmental estrogenic agent bisphenol A (BPA). The highest activity toward this chemical is reported for human and rodent UGT2 enzymes. Surprisingly, our studies using the DeltaUgt2 mice demonstrate that, while both UGT1 and UGT2 isoforms can conjugate BPA, clearance is largely dependent on UGT1s. PMID- 26354951 TI - The Reliability of Estimating Ki Values for Direct, Reversible Inhibition of Cytochrome P450 Enzymes from Corresponding IC50 Values: A Retrospective Analysis of 343 Experiments. AB - In the present study, we conducted a retrospective analysis of 343 in vitro experiments to ascertain whether observed (experimentally determined) values of Ki for reversible cytochrome P450 (P450) inhibition could be reliably predicted by dividing the corresponding IC50 values by two, based on the relationship (for competitive inhibition) in which Ki = IC50/2 when [S] (substrate concentration) = Km (Michaelis-Menten constant). Values of Ki and IC50 were determined under the following conditions: 1) the concentration of P450 marker substrate, [S], was equal to Km (for IC50 determinations) and spanned Km (for Ki determinations); 2) the substrate incubation time was short (5 minutes) to minimize metabolism dependent inhibition and inhibitor depletion; and 3) the concentration of human liver microsomes was low (0.1 mg/ml or less) to maximize the unbound fraction of inhibitor. Under these conditions, predicted Ki values, based on IC50/2, correlated strongly with experimentally observed Ki determinations [r = 0.940; average fold error (AFE) = 1.10]. Of the 343 predicted Ki values, 316 (92%) were within a factor of 2 of the experimentally determined Ki values, and only one value fell outside a 3-fold range. In the case of noncompetitive inhibitors, Ki values predicted from IC50/2 values were overestimated by a factor of nearly 2 (AFE = 1.85; n = 13), which is to be expected because, for noncompetitive inhibition, Ki = IC50 (not IC50/2). The results suggest that, under appropriate experimental conditions with the substrate concentration equal to Km, values of Ki for direct, reversible inhibition can be reliably estimated from values of IC50/2. PMID- 26354952 TI - Framework for 21st-Century School Nursing Practice: Implications for Research. PMID- 26354953 TI - Response to "Fluticasone or Montelukast in Preschool Wheeze: A Randomized Controlled Trial". PMID- 26354954 TI - Commentary: The Wright Ross Salk Award: Reflections on Service With a Purpose. PMID- 26354955 TI - Guidelines for the Care and Welfare of Cephalopods in Research -A consensus based on an initiative by CephRes, FELASA and the Boyd Group. AB - This paper is the result of an international initiative and is a first attempt to develop guidelines for the care and welfare of cephalopods (i.e. nautilus, cuttlefish, squid and octopus) following the inclusion of this Class of ~700 known living invertebrate species in Directive 2010/63/EU. It aims to provide information for investigators, animal care committees, facility managers and animal care staff which will assist in improving both the care given to cephalopods, and the manner in which experimental procedures are carried out. Topics covered include: implications of the Directive for cephalopod research; project application requirements and the authorisation process; the application of the 3Rs principles; the need for harm-benefit assessment and severity classification. Guidelines and species-specific requirements are provided on: i. supply, capture and transport; ii. environmental characteristics and design of facilities (e.g. water quality control, lighting requirements, vibration/noise sensitivity); iii. accommodation and care (including tank design), animal handling, feeding and environmental enrichment; iv. assessment of health and welfare (e.g. monitoring biomarkers, physical and behavioural signs); v. approaches to severity assessment; vi. disease (causes, prevention and treatment); vii. scientific procedures, general anaesthesia and analgesia, methods of humane killing and confirmation of death. Sections covering risk assessment for operators and education and training requirements for carers, researchers and veterinarians are also included. Detailed aspects of care and welfare requirements for the main laboratory species currently used are summarised in Appendices. Knowledge gaps are highlighted to prompt research to enhance the evidence base for future revision of these guidelines. PMID- 26354956 TI - Left ventricular free wall rupture contained by an apical pseudo-aneurysm. PMID- 26354957 TI - Music and the heart. AB - Music can powerfully evoke and modulate emotions and moods, along with changes in heart activity, blood pressure (BP), and breathing. Although there is great heterogeneity in methods and quality among previous studies on effects of music on the heart, the following findings emerge from the literature: Heart rate (HR) and respiratory rate (RR) are higher in response to exciting music compared with tranquilizing music. During musical frissons (involving shivers and piloerection), both HR and RR increase. Moreover, HR and RR tend to increase in response to music compared with silence, and HR appears to decrease in response to unpleasant music compared with pleasant music. We found no studies that would provide evidence for entrainment of HR to musical beats. Corresponding to the increase in HR, listening to exciting music (compared with tranquilizing music) is associated with a reduction of heart rate variability (HRV), including reductions of both low-frequency and high-frequency power of the HRV. Recent findings also suggest effects of music-evoked emotions on regional activity of the heart, as reflected in electrocardiogram amplitude patterns. In patients with heart disease (similar to other patient groups), music can reduce pain and anxiety, associated with lower HR and lower BP. In general, effects of music on the heart are small, and there is great inhomogeneity among studies with regard to methods, findings, and quality. Therefore, there is urgent need for systematic high-quality research on the effects of music on the heart, and on the beneficial effects of music in clinical settings. PMID- 26354958 TI - Erratum: Dual-Hormone Changes Are Related to Bargaining Performance. PMID- 26354959 TI - Retraction of "A Common Discrete Resource for Visual Working Memory and Visual Search". PMID- 26354960 TI - Coronary artery involvement in Kawasaki disease. PMID- 26354961 TI - Numerical analysis of the 3-dimensional aortic root morphology during the cardiac cycle. AB - OBJECTIVES: The aim was to define the 3-dimensional (3D) geometrical changes of the aortic root and to determine the local shear stress profile of aortic root elements during the cardiac cycle. METHODS: Six sonomicrometric crystals (200 Hz) were implanted into the aortic root of five pigs at the commissures and at the aortic root base (AoB). 3D aortic root deformation including volume, torsion and tilt angle were determined. Geometrical data with measured local flow and pressure conditions was used for computed fluid dynamics modelling of the aortic root. RESULTS: Compared with end-diastole, the sinotubular junction and AoB have maximal expansion at peak ejection: 16.42 +/- 6.36 and 7.60 +/- 2.52%, and minimal at isovolaemic relaxation: 2.87 +/- 1.62 and 1.85 +/- 1.79%. Aortic root tilt and rotation angle were maximal at the end of diastole: 17.7 +/- 8.8 and 21.2 +/- 2.09 degrees , and decreased to 15.24 +/- 8.14 and 18.3 +/- 0.1.94 degrees at peak ejection. High shear stress >20 Pa was registered at peak ejection at coaptations, and during diastole at the superior two-thirds of the leaflets and intervalvular triangles (IVTs). The leaflet body, inferior one-third of the IVTs and valve nadir were exposed to moderate shear stress (8-16 Pa) during the cardiac cycle. CONCLUSIONS: Aortic root geometry demonstrates precise 3D changes of tilt and rotation angle. Reduction of angles during ejection results in a straight cylinder with low shear stress that facilitates the ejection; the increase during diastole results in a tilted frustum with elevated shear stress. Findings can be used for comparative analysis of native and synthetic structures with individual compliance. PMID- 26354962 TI - Effect of the T-type channel blocker KYS-05090S in mouse models of acute and neuropathic pain. AB - T-type channels are important contributors to the initiation and the maintenance of chronic pain states. Blocking T-type channels is therefore a possible therapeutic strategy for relieving pain. Here, we report the Cav3.2 T-type channel blocking action of a previously reported small organic molecule, KYS 05090S. This compound was able to reduce transiently expressed Cav3.2 currents with low micromolar affinity and mediated a hyperpolarizing shift in half inactivation potential. KYS-05090S was then tested in models of acute and neuropathic pain. KYS-05090S (10 MUg/10 MUl delivered intrathecally) significantly reduced acute pain induced by formalin in both the tonic and inflammatory phases. Its antinociceptive effect was not observed when delivered to Cav3.2 null-mice revealing a Cav3.2-dependent mechanism. KYS-05090S also reduced neuropathic pain in a model of partial sciatic nerve injury. Those results indicate that KYS-05090S mediates a potent analgesic effect in inflammatory and neuropathic pain through T-type channel modulation, suggesting that its scaffold could be explored as a new class of analgesic compounds. PMID- 26354963 TI - Metabolic syndrome is not only a risk factor for cardiovascular diseases in systemic lupus erythematosus but is also associated with cumulative organ damage: a cross-sectional analysis of 311 patients. AB - BACKGROUND/PURPOSE: Patients with systemic lupus erythematosus (SLE) have increased rates of cardiovascular disease (CVD) that are one of the major causes of mortality. The aim of this study was to determine the frequencies of metabolic syndrome (MetS) and CVD in SLE patients and investigate the link between these and clinical features of SLE. METHODS: A total of 311 SLE patients were consecutively assessed for cumulative organ damage (SDI/SLICC scores), history of CVD and MetS as defined by the National Cholesterol Educational Program Adult Treatment Panel III (NCEP ATP III). Clinical data of SLE patients were collected from the records. RESULTS: The mean age of the patients was 40.2 +/- 13.4 years and 89% were female. The frequencies of CVD and MetS were 15.2% and 19%, respectively. In this SLE cohort increased age, cumulative damage, disease duration and CVD were associated with MetS. CVD was associated with disease duration, cumulative damage, pericarditis, hematologic involvement, lymphopenia, thrombocytopenia, neurological involvement and antiphospholipid antibody (aPL) positivity. Hydroxychloroquine (HCQ) use was found as a protective factor for CVD. CONCLUSION: In SLE patients, MetS was associated with CVD and both increased with disease duration. Patients who developed MetS and/or CVD had increased cumulative organ damage. Certain clinical features of SLE and the presence of aPL were also associated with CVD. There was a significant protective effect of HCQ from CVD. The prevention of MetS and long-term use of HCQ may be beneficial in improving the prognosis of SLE. PMID- 26354964 TI - Single test isolated lupus anticoagulant positivity is associated with increased plasma levels of inflammatory markers and dyslipidemia. AB - OBJECTIVE: To investigate whether a single positive test for lupus anticoagulant (LA) is associated with levels of inflammatory markers and traditional cardiovascular risk factors, independent of autoimmune disease, thrombophilia and occurrence of other antiphospholipid antibodies. METHODS: In a retrospective observational study we included persons referred for thrombophilia testing during 2011-2014. Persons with autoimmune disease, thrombophilia or presence of specific anti-phospholipid antibodies were excluded. Multivariate logistic regression analyses adjusted for age and sex was performed and odds ratios (ORs) with 95% confidence intervals (95% CI) calculated. RESULTS: Of 381 individuals tested, 271 fulfilled the criteria, of whom 22 (8%) were LA positive and 249 (92%) LA negative. LA positivity was associated with higher body mass index (BMI) (OR 1.12, 95% CI: 1.03-1.23, p = 0.01); C-reactive protein (OR 1.08 95% CI:1.04-1.11, p < 0.001); fibrinogen (OR 1.51 95% CI: 1.27-1.78, p < 0.001); coagulation factor VIII (FVIII) (OR 1.73 95% CI: 1.01-2.96, p = 0.046), low high density lipoprotein (HDL) (OR 0.03 95% CI: 0.00-0.19, p < 0.001) and high triglyceride (OR 1.81 95% CI: 1.12-2.92, p = 0.02) compared with LA negative individuals. CONCLUSION: This study shows that single test isolated LA positivity is associated with increased levels of inflammatory markers, low HDL cholesterol, elevated triglyceride and high BMI. PMID- 26354965 TI - Colistin-associated Acute Kidney Injury in Severely Ill Patients: A Step Toward a Better Renal Care? A Prospective Cohort Study. AB - BACKGROUND: Critically ill patients with severe sepsis or septic shock may need relatively high colistin daily doses for efficacy against multidrug-resistant and extensively drug-resistant gram-negative rods. However, acute kidney injury (AKI) may represent a major dose-limiting adverse effect of colistin. We sought to determine AKI occurrence and to identify factors influencing AKI risk in severely ill patients receiving colistin according to a recently proposed dosing strategy. METHODS: A prospective, observational, cohort study involving patients with severe sepsis or septic shock who received colistin was performed. AKI was defined according to Acute Kidney Injury Network criteria. Colistin administration was driven by a modified pharmacokinetics-pharmacodynamics (PK/PD) based dosing approach. RESULTS: Of 70 patients who received colistin at a median daily dose of 9 million IU (MIU; interquartile range, 5.87-11.1 MIU), 31 (44%) developed AKI. In univariate analysis, age, Acute Physiology and Chronic Health Evaluation (APACHE) II score, Sequential Organ Failure Assessment (SOFA), score and baseline renal impairment were significantly associated with AKI. Moreover, patients with AKI were less frequently treated with adjuvant ascorbic acid (P = .003). In multivariate analysis, independent predictors of AKI were baseline renal impairment (adjusted hazard ratio, 4.15; 95% confidence interval, 1.9-9.2; P < .001) and age (1.03; 1.0-1.05; P = .028), whereas a strong independent renal protective role emerged for ascorbic acid (0.27; .12-.57; P < .001). CONCLUSIONS: In severely ill patients receiving colistin according to a PK/PD-driven dosing approach, baseline renal impairment and older age strongly predict AKI occurrence, but concomitant administration of ascorbic acid markedly reduces AKI risk, allowing safer use of colistin. PMID- 26354966 TI - Optimal Usage of Colistin: Are We Any Closer? PMID- 26354969 TI - Pneumococcal Vaccination: Should We Kill the Enemy or Just Disarm It? PMID- 26354968 TI - Viral Hemorrhagic Fever Diagnostics. AB - There are 4 families of viruses that cause viral hemorrhagic fever (VHF), including Filoviridae. Ebola virus is one virus within the family Filoviridae and the cause of the current outbreak of VHF in West Africa. VHF-endemic areas are found throughout the world, yet traditional diagnosis of VHF has been performed in large reference laboratories centered in Europe and the United States. The large amount of capital needed, as well as highly trained and skilled personnel, has limited the availability of diagnostics in endemic areas except in conjunction with governmental and nongovernmental entities. However, rapid diagnosis of VHF is essential to efforts that will limit outbreaks. In addition, increased global travel suggests VHF diagnoses may be made outside of the endemic areas. Thus, understanding how to diagnose VHF is imperative for laboratories worldwide. This article reviews traditional and current diagnostic modalities for VHF. PMID- 26354971 TI - Healthcare Workers and Post-Elimination Era Measles: Lessons on Acquisition and Exposure Prevention. AB - BACKGROUND: When caring for measles patients, N95 respirator use by healthcare workers (HCWs) with documented immunity is not uniformly required or practiced. In the setting of increasingly common measles outbreaks and provider inexperience with measles, HCWs face increased risk for occupational exposures. Meanwhile, optimal infection prevention responses to healthcare-associated exposures are loosely defined. We describe measles acquisition among HCWs despite prior immunity and lessons from healthcare-associated exposure investigations during a countywide outbreak. METHODS: Primary and secondary cases, associated exposures, and risk factors were identified during a measles outbreak in Orange County, California from, 30 January 2014 to 21 April 2014. We reviewed the effect of different strategies in response to hospital exposures and resultant case capture. RESULTS: Among 22 confirmed measles cases, 5 secondary cases occurred in HCWs. Of these, 4 had direct contact with measles patients; none wore N95 respirators. Four HCWs had prior evidence of immunity and continued working after developing symptoms, resulting in 1014 exposures, but no transmissions. Overall, 13 of 15 secondary cases had face-to-face contact with measles patients, 8 with prior evidence of immunity. CONCLUSIONS: HCWs with unmasked, direct contact with measles patients are at risk for developing disease despite evidence of prior immunity, resulting in potentially large numbers of exposures and necessitating time-intensive investigations. Vaccination may lower infectivity. Regardless of immunity status, HCWs should wear N-95 respirators (or equivalent) when evaluating suspected measles patients. Those with direct unprotected exposure should be monitored for symptoms and be furloughed at the earliest sign of illness. PMID- 26354970 TI - Invasive Pneumococcal Disease Among Immunocompromised Persons: Implications for Vaccination Programs. AB - BACKGROUND: In 2012/2013, a single dose of 13-valent pneumococcal conjugate vaccine (PCV13) was recommended for immunocompromised adults in the United States and Canada. To assess the potential benefits of this recommendation, we assessed the serotype-specific burden of invasive pneumococcal disease (IPD) among immunocompromised individuals. METHODS: From 1995 to 2012, population-based surveillance for IPD was conducted in Metropolitan Toronto and Peel Region, Canada. Disease incidence and case fatality were measured in immunocompromised populations over time, and the contribution of different serotypes determined. RESULTS: Overall, 2115/7604 (28%) episodes of IPD occurred in immunocompromised persons. IPD incidence was 12-fold higher (95% confidence interval [CI], 8.7-15) in immunocompromised compared to immunocompetent persons; the case fatality rate was elevated in both younger (odds ratio [OR] 1.8) and older (OR 1.3) adults. Use of immunosuppressive medications was associated with a 2.1-2.7 fold increase in the risk of IPD. Five years after PPV23 program implementation, IPD incidence had declined significantly in immunocompromised adults (IRR 0.57, 95% CI, .40-.82). Ten years after pediatric PCV7 authorization, IPD due to PCV7 serotypes had decreased by 90% (95% CI, 77%-96%) in immunocompromised persons of all ages. In 2011/2012, 37% of isolates causing IPD in immunocompromised persons were PCV13 serotypes and 27% were PPV23/not PCV13 serotypes. CONCLUSIONS: Immunocompromised individuals comprised 28% of IPD. Both PPV23 and herd immunity from pediatric PCV7 were associated with reductions in IPD in immunocompromised populations. PCV13 vaccination of immunocompromised adults may substantially reduce the residual burden until herd immunity from pediatric PCV13 is fully established. PMID- 26354972 TI - Management of Brugada Syndrome: Thirty-Three-Year Experience Using Electrophysiologically Guided Therapy With Class 1A Antiarrhythmic Drugs. AB - BACKGROUND: Information on long-term clinical outcome of patients with Brugada syndrome treated with electrophysiologically guided class 1A antiarrhythmic drugs (AAD) is limited. METHODS AND RESULTS: An aggressive protocol of programmed ventricular stimulation was performed in 96 patients with Brugada syndrome (88% males; mean age, 39.8+/-15.9 years). Ten patients were cardiac arrest survivors, 27 had presented with syncope, and 59 were asymptomatic. Ventricular fibrillation was induced in 66 patients, including 100%, 74%, and 61% of patients with cardiac arrest, syncope, and no symptoms, respectively. All but 6 of the 66 patients with inducible ventricular fibrillation underwent electrophysiological testing on quinidine (n=54), disopyramide (n=2), or both (n=4). Fifty-four (90%) patients were electrophysiological responders to >1 AAD with similar efficacy rates (~90%) in all patients groups. Patients with no inducible ventricular fibrillation at baseline were left on no therapy. After a mean follow-up of 113.3+/-71.5 months, 92 patients were alive, whereas 4 died from noncardiac causes. No arrhythmic event occurred during class 1A AAD therapy in any of electrophysiological drug responders and in patients with no baseline inducible ventricular fibrillation. Arrhythmic events occurred in only 2 cardiac arrest survivors treated with implantable cardioverter-defibrillator alone but did not recur on quinidine. All cases of recurrent syncope (n=12) were attributed to a vasovagal (n=10) or nonarrhythmic mechanism (n=2). Class 1A AAD therapy resulted in 38% incidence of side effects that resolved after drug discontinuation. CONCLUSIONS: Our data suggest that electrophysiologically guided class 1A AAD treatment has a place in our therapeutic armamentarium for all types of patients with Brugada syndrome. PMID- 26354973 TI - Genetic Diversity and Societally Important Disparities. AB - The magnitude of genetic diversity within human populations varies in a way that reflects the sequence of migrations by which people spread throughout the world. Beyond its use in human evolutionary genetics, worldwide variation in genetic diversity sometimes can interact with social processes to produce differences among populations in their relationship to modern societal problems. We review the consequences of genetic diversity differences in the settings of familial identification in forensic genetic testing, match probabilities in bone marrow transplantation, and representation in genome-wide association studies of disease. In each of these three cases, the contribution of genetic diversity to social differences follows from population-genetic principles. For a fourth setting that is not similarly grounded, we reanalyze with expanded genetic data a report that genetic diversity differences influence global patterns of human economic development, finding no support for the claim. The four examples describe a limit to the importance of genetic diversity for explaining societal differences while illustrating a distinction that certain biologically based scenarios do require consideration of genetic diversity for solving problems to which populations have been differentially predisposed by the unique history of human migrations. PMID- 26354974 TI - Sorting Out Identities: An Educational Primer for Use with "Novel Tools for Genetic Manipulation of Follicle Stem Cells in the Drosophila Ovary Reveal an Integrin-Dependent Transition from Quiescence to Proliferation". AB - Organisms are made up of thousands of different cell types that must migrate, proliferate, and interact with each other to yield functional organ systems and ultimately a viable organism. A characteristic that distinguishes one cell type from another is the set of genes that it expresses. An article by Hartman et al. in the April 2015 issue of GENETICS identified methods to uniquely identify different cell populations during oogenesis, providing valuable tools for future studies. This Primer article provides background information on the Drosophila ovary as a system in which to study stem cell regulation, mechanisms for regulating gene expression, and the techniques used by Hartman et al. to identify specific cell populations and study their function. PMID- 26354977 TI - Corrigendum. PMID- 26354975 TI - Synapse-Assembly Proteins Maintain Synaptic Vesicle Cluster Stability and Regulate Synaptic Vesicle Transport in Caenorhabditis elegans. AB - The functional integrity of neurons requires the bidirectional active transport of synaptic vesicles (SVs) in axons. The kinesin motor KIF1A transports SVs from somas to stable SV clusters at synapses, while dynein moves them in the opposite direction. However, it is unclear how SV transport is regulated and how SVs at clusters interact with motor proteins. We addressed these questions by isolating a rare temperature-sensitive allele of Caenorhabditis elegans unc-104 (KIF1A) that allowed us to manipulate SV levels in axons and dendrites. Growth at 20 degrees and 14 degrees resulted in locomotion rates that were ~3 and 50% of wild type, respectively, with similar effects on axonal SV levels. Corresponding with the loss of SVs from axons, mutants grown at 14 degrees and 20 degrees showed a 10- and 24-fold dynein-dependent accumulation of SVs in their dendrites. Mutants grown at 14 degrees and switched to 25 degrees showed an abrupt irreversible 50% decrease in locomotion and a 50% loss of SVs from the synaptic region 12-hr post-shift, with no further decreases at later time points, suggesting that the remaining clustered SVs are stable and resistant to retrograde removal by dynein. The data further showed that the synapse-assembly proteins SYD-1, SYD-2, and SAD-1 protected SV clusters from degradation by motor proteins. In syd-1, syd-2, and sad-1 mutants, SVs accumulate in an UNC-104 dependent manner in the distal axon region that normally lacks SVs. In addition to their roles in SV cluster stability, all three proteins also regulate SV transport. PMID- 26354976 TI - UNC-16 (JIP3) Acts Through Synapse-Assembly Proteins to Inhibit the Active Transport of Cell Soma Organelles to Caenorhabditis elegans Motor Neuron Axons. AB - The conserved protein UNC-16 (JIP3) inhibits the active transport of some cell soma organelles, such as lysosomes, early endosomes, and Golgi, to the synaptic region of axons. However, little is known about UNC-16's organelle transport regulatory function, which is distinct from its Kinesin-1 adaptor function. We used an unc-16 suppressor screen in Caenorhabditis elegans to discover that UNC 16 acts through CDK-5 (Cdk5) and two conserved synapse assembly proteins: SAD-1 (SAD-A Kinase), and SYD-2 (Liprin-alpha). Genetic analysis of all combinations of double and triple mutants in unc-16(+) and unc-16(-) backgrounds showed that the three proteins (CDK-5, SAD-1, and SYD-2) are all part of the same organelle transport regulatory system, which we named the CSS system based on its founder proteins. Further genetic analysis revealed roles for SYD-1 (another synapse assembly protein) and STRADalpha (a SAD-1-interacting protein) in the CSS system. In an unc-16(-) background, loss of the CSS system improved the sluggish locomotion of unc-16 mutants, inhibited axonal lysosome accumulation, and led to the dynein-dependent accumulation of lysosomes in dendrites. Time-lapse imaging of lysosomes in CSS system mutants in unc-16(+) and unc-16(-) backgrounds revealed active transport defects consistent with the steady-state distributions of lysosomes. UNC-16 also uses the CSS system to regulate the distribution of early endosomes in neurons and, to a lesser extent, Golgi. The data reveal a new and unprecedented role for synapse assembly proteins, acting as part of the newly defined CSS system, in mediating UNC-16's organelle transport regulatory function. PMID- 26354979 TI - Transient focal left ventricular ballooning: a new variant of Takotsubo cardiomyopathy. PMID- 26354980 TI - Cardiac morphology and function reference values derived from a large subset of healthy young Caucasian adults by magnetic resonance imaging. AB - AIMS: Assessment of cardiac anatomy and function by cardiovascular magnetic resonance (CMR) is accurate and reproducible and is commonly performed to clarify borderline results obtained by other techniques. Normal reference values are lacking in a large sample of young healthy adults. As CMR is increasingly solicited to discriminate normality from equivocal disease in this population, we sought to determine reliable reference values. METHODS AND RESULTS: A sample of 434 Caucasian adults aged 26 +/- 4 years (45% male) without cardiovascular disease or risk factors (including obesity and smoking) underwent CMR. Blood pressure, electrocardiogram, and plasma markers (lipid profile, fasting glucose, troponin, and Nt-pro-BNP) were within normal limits and typical of a low cardiometabolic-risk profile. End-diastolic (ED), end-systolic (ES), and stroke volumes were greater in men for left and right atria and ventricles. Left ventricular (LV) mass was higher in men. ED wall thickness of all segments was greater in men, whereas ES wall thickening (segmental function) was similar in both genders. After normalization to body surface area, all gender differences remained. Left and right ventricular volumes were lower, and left atrial volumes were higher in older individuals. In contrast, LV mass was not associated with age. CONCLUSION: This is the first large database of reference ranges for ventricular and atrial functions, volumes, and mass in young Caucasian men and women devoid of cardiovascular disease and risk factors. These data will contribute to improving the accuracy of CMR interpretation for clinical and research applications. PMID- 26354981 TI - A geographical cluster of progressive supranuclear palsy in northern France. AB - OBJECTIVE: To describe a cluster of progressive supranuclear palsy (PSP) in northern France. PSP has not been reported in geographical, temporal, or occupational clusters. A unit of Neurology and Neurogeriatrics opened in 2005 at the Centre Hospitalier de Wattrelos, serving the population of Wattrelos and Leers (combined population 51,551) and parts of neighboring towns. For most of the 20th century, this area was a center for chromate and phosphate ore processing, textile dyeing, and tanning. Significant industrial waste persists close to residential areas. METHODS: From 2005 to 2014, 92 patients with PSP at Centre Hospitalier de Wattrelos were identified and studied. Detailed residential data were available in the medical records. Eighty cases have had magnetic resonance head scanning and 60 have died, of whom 13 have been examined neuropathologically. RESULTS: The ratio of observed to expected PSP incidence over the period 2005 to 2012 was 12.3 (95% confidence interval: 7.4-35.9). Mean onset age was 74.3 years. The Richardson syndrome/PSP-parkinsonism ratio was 43%/42%. Four other phenotypes each occurred in 2% to 5%. Onset was gait/balance difficulty in 52%. None of the 92 affected patients were relatives and 7 were of North African ancestry. MRI was compatible with a clinical diagnostic of PSP in all cases. Histopathologic examination confirmed neurofibrillary degeneration and tufted astrocytes in all autopsied cases. Western blots revealed a typical tau 4R doublet. The tau H1 haplotype occurred in 95.8% of cases' chromosomes. CONCLUSIONS: We have identified a cluster of PSP in a geographical area with severe environmental contamination by industrial metals. PMID- 26354983 TI - Comment: CAG repeats in idiopathic Parkinson disease-To screen or not to screen. PMID- 26354982 TI - Detailed comparison of amyloid PET and CSF biomarkers for identifying early Alzheimer disease. AB - OBJECTIVE: To compare the diagnostic accuracy of CSF biomarkers and amyloid PET for diagnosing early-stage Alzheimer disease (AD). METHODS: From the prospective, longitudinal BioFINDER study, we included 122 healthy elderly and 34 patients with mild cognitive impairment who developed AD dementia within 3 years (MCI-AD). beta-Amyloid (Abeta) deposition in 9 brain regions was examined with [18F] flutemetamol PET. CSF was analyzed with INNOTEST and EUROIMMUN ELISAs. The results were replicated in 146 controls and 64 patients with MCI-AD from the Alzheimer's Disease Neuroimaging Initiative study. RESULTS: The best CSF measures for identifying MCI-AD were Abeta42/total tau (t-tau) and Abeta42/hyperphosphorylated tau (p-tau) (area under the curve [AUC] 0.93-0.94). The best PET measures performed similarly (AUC 0.92-0.93; anterior cingulate, posterior cingulate/precuneus, and global neocortical uptake). CSF Abeta42/t-tau and Abeta42/p-tau performed better than CSF Abeta42 and Abeta42/40 (AUC difference 0.03-0.12, p<0.05). Using nonoptimized cutoffs, CSF Abeta42/t-tau had the highest accuracy of all CSF/PET biomarkers (sensitivity 97%, specificity 83%). The combination of CSF and PET was not better than using either biomarker separately. CONCLUSIONS: Amyloid PET and CSF biomarkers can identify early AD with high accuracy. There were no differences between the best CSF and PET measures and no improvement when combining them. Regional PET measures were not better than assessing the global Abeta deposition. The results were replicated in an independent cohort using another CSF assay and PET tracer. The choice between CSF and amyloid PET biomarkers for identifying early AD can be based on availability, costs, and doctor/patient preferences since both have equally high diagnostic accuracy. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that amyloid PET and CSF biomarkers identify early-stage AD equally accurately. PMID- 26354984 TI - Comment: Progressive supranuclear palsy and environmental toxins. PMID- 26354985 TI - Comment: Altered sphingolipid metabolism--A marker for episodic migraine? PMID- 26354986 TI - Is normosmic Parkinson disease a unique clinical phenotype? AB - OBJECTIVE: Olfactory dysfunction is present in the majority of patients with early-stage Parkinson disease (PD) and can precede the onset of motor symptoms by many years. We performed this study to evaluate whether normosmic patients with PD had different clinical features compared to hyposmic patients. METHODS: We analyzed the data of 208 de novo patients with PD (mean age, 65.4 +/- 9.7 years; range, 38-85 years; 104 men) who underwent both olfactory function tests and dopamine transporter (DAT) scans. RESULTS: Normosmic patients were significantly younger and had fewer motor deficits than hyposmic patients with PD. Striatal subregional DAT activities were comparable between the 2 groups, but intersubregional gradients were significantly higher in normosmic than hyposmic PD. A general linear model showed that normosmic patients with PD showed significantly fewer motor deficits after controlling the patient's age, sex, symptom duration, and DAT activity in the posterior putamen (p = 0.016). Levodopa equivalent dose at approximately 2.5 years follow-up tended to be lower in normosmic than in hyposmic PD (p = 0.055). CONCLUSIONS: These results suggest that normosmic PD is a unique clinical phenotype with a more benign course, compared to hyposmic PD. Either less pathologic involvement in the olfactory system or a greater potential for olfactory neurogenesis in normosmic PD may contribute to this benign process compared to hyposmic PD. PMID- 26354987 TI - The olfactory side of Parkinson disease: Relevance for clinical practice. PMID- 26354988 TI - Evaluation of outcome measures for neurogenic claudication: A patient-centered approach. AB - OBJECTIVES: To determine whether patients with neurogenic claudication associated with lumbar spinal stenosis would prefer a treatment that makes it possible for them to walk farther or walk with less pain; to examine associations between this treatment preference and patient-reported and in-clinic treadmill testing measures of walking ability and walking-associated pain. METHODS: In this cross sectional study, 269 patients with neurogenic claudication were asked to report their pain intensity when walking, complete the Swiss Spinal Stenosis Questionnaire, rank their outcome preferences for treatment, and undergo standardized treadmill testing, including measures of final pain rating and time to first pain of moderate intensity (Tfirst). Descriptive statistics were used to characterize patient preferences for treatment outcome. Associations between self report questionnaires and standardized treadmill testing outcomes were evaluated using Spearman correlations. RESULTS: Seventy-nine percent of patients expressed a preference for treatment that allowed them to walk with less pain. Preference for reduced pain was associated with higher pain during daily walking, along with a shorter Tfirst and higher final pain severity on treadmill testing. In contrast, patient preference for treatment outcome was not associated with self reported measures of daily walking capacity or walking distance on the treadmill. CONCLUSIONS: A majority of patients with neurogenic claudication prioritized walking with reduced pain over walking farther. Reduction in pain while walking may therefore constitute a sufficient patient-focused treatment outcome for the majority of these patients. These results have implications for clinical trial design and assessment of treatment efficacy in neurogenic claudication. PMID- 26354991 TI - Combretastatins: more than just vascular targeting agents? AB - Several prodrugs of the naturally occurring combretastatins have undergone extensive clinical evaluation as vascular targeting agents (VTAs). Their increased selectivity toward endothelial cells together with their innate ability to rapidly induce vascular shutdown and inhibit tumor growth at doses up to 10 fold less than the maximum tolerated dose led to the clinical evaluation of combretastatins as VTAs. Tubulin is well established as the molecular target of the combretastatins and the vast majority of its synthetic derivatives. Furthermore, tubulin is a highly validated molecular target of many direct anticancer agents routinely used as front-line chemotherapeutics. The unique vascular targeting properties of the combretastatins have somewhat overshadowed their development as direct anticancer agents and the delineation of the various cell death pathways and anticancer properties associated with such chemotherapeutics. Moreover, the ongoing clinical trial of OXi4503 (combretastatin-A1 diphosphate) together with preliminary preclinical evaluation for the treatment of refractory acute myelogenous leukemia has successfully highlighted both the indirect and direct anticancer properties of combretastatins. In this review, we discuss the development of the combretastatins from nature to the clinic. The various mechanisms underlying combretastatin-induced cell cycle arrest, mitotic catastrophe, cell death, and survival are also reviewed in an attempt to further enhance the clinical prospects of this unique class of VTAs. PMID- 26354990 TI - Interictal, circulating sphingolipids in women with episodic migraine: A case control study. AB - OBJECTIVE: To evaluate interictal, circulating sphingolipids in women migraineurs. METHODS: In the fasting state, serum samples were obtained pain-free from 88 women with episodic migraine (EM; n=52) and from controls (n=36). Sphingolipids were detected and quantified by high-performance liquid chromatography coupled with tandem mass spectrometry using multiple reaction monitoring. Multivariate logistic regression was used to examine the association between serum sphingolipids and EM odds. A recursive partitioning decision tree based on the serum concentrations of 10 sphingolipids was used to determine the presence or absence of EM in a subset of participants. RESULTS: Total ceramide (EM 6,502.9 ng/mL vs controls 10,518.5 ng/mL; p<0.0001) and dihydroceramide (EM 39.3 ng/mL vs controls 63.1 ng/mL; p<0.0001) levels were decreased in those with EM as compared with controls. Using multivariate logistic regression, each SD increase in total ceramide (odds ratio [OR] 0.07; 95% confidence interval [CI]: 0.02, 0.22; p<0.001) and total dihydroceramide (OR 0.05; 95% CI: 0.01, 0.21; p<0.001) levels was associated with more than 92% reduced odds of migraine. Although crude sphingomyelin levels were not different in EM compared with controls, after adjustments, every SD increase in the sphingomyelin species C18:0 (OR 4.28; 95% CI: 1.87, 9.81; p=0.001) and C18:1 (OR 2.93; 95% CI: 1.55, 5.54; p=0.001) was associated with an increased odds of migraine. Recursive portioning models correctly classified 14 of 14 randomly selected participants as EM or control. CONCLUSION: These results suggest that sphingolipid metabolism is altered in women with EM and that serum sphingolipid panels may have potential to differentiate EM presence or absence. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that serum sphingolipid panels accurately distinguish women with migraine from women without migraine. PMID- 26354992 TI - Inhibition of mitogen-activated protein kinases/nuclear factor kappaB-dependent inflammation by a novel chalcone protects the kidney from high fat diet-induced injuries in mice. AB - The prevalence of obesity has increased dramatically worldwide leading to increases in obesity-related complications, such as obesity-related glomerulopathy (ORG). Obesity is a state of chronic, low-grade inflammation, and increased inflammation in the adipose and kidney tissues has been shown to promote the progression of renal damage in obesity. Current therapeutic options for ORG are fairly limited and, as a result, we are seeing increased rates of progression to end-stage renal disease. Chalcones are a class of naturally occurring compounds with various pharmacological properties. 1-(3,4 Dihydroxyphenyl)-3-(2-methoxyphenyl)prop-2-en-1-one (L2H17) is a chalcone that we have previously synthesized and found capable of inhibiting the lipopolysaccharide-induced inflammatory response in macrophages. In this study, we investigated L2H17's effect on obesity-induced renal injury using palmitic acid-induced mouse peritoneal macrophages and high fat diet-fed mice. Our results indicate that L2H17 protects against renal injury through the inhibition of the mitogen-activated protein kinase/nuclear factor kappaB pathways significantly by decreasing the expression of proinflammatory cytokines and cell adhesion molecules and improving kidney histology and pathology. These findings lead us to believe that L2H17, as an anti-inflammatory agent, can be a potential therapeutic option in treating ORG. PMID- 26354989 TI - Large-scale assessment of polyglutamine repeat expansions in Parkinson disease. AB - OBJECTIVES: We aim to clarify the pathogenic role of intermediate size repeat expansions of SCA2, SCA3, SCA6, and SCA17 as risk factors for idiopathic Parkinson disease (PD). METHODS: We invited researchers from the Genetic Epidemiology of Parkinson's Disease Consortium to participate in the study. There were 12,346 cases and 8,164 controls genotyped, for a total of 4 repeats within the SCA2, SCA3, SCA6, and SCA17 genes. Fixed- and random-effects models were used to estimate the summary risk estimates for the genes. We investigated between study heterogeneity and heterogeneity between different ethnic populations. RESULTS: We did not observe any definite pathogenic repeat expansions for SCA2, SCA3, SCA6, and SCA17 genes in patients with idiopathic PD from Caucasian and Asian populations. Furthermore, overall analysis did not reveal any significant association between intermediate repeats and PD. The effect estimates (odds ratio) ranged from 0.93 to 1.01 in the overall cohort for the SCA2, SCA3, SCA6, and SCA17 loci. CONCLUSIONS: Our study did not support a major role for definite pathogenic repeat expansions in SCA2, SCA3, SCA6, and SCA17 genes for idiopathic PD. Thus, results of this large study do not support diagnostic screening of SCA2, SCA3, SCA6, and SCA17 gene repeats in the common idiopathic form of PD. Likewise, this largest multicentered study performed to date excludes the role of intermediate repeats of these genes as a risk factor for PD. PMID- 26354993 TI - Efflux transporters at the blood-brain barrier limit delivery and efficacy of cyclin-dependent kinase 4/6 inhibitor palbociclib (PD-0332991) in an orthotopic brain tumor model. AB - 6-Acetyl-8-cyclopentyl-5-methyl-2-([5-(piperazin-1-yl)pyridin-2 yl]amino)pyrido(2,3-d)pyrimidin-7(8H)-one [palbociclib (PD-0332991)] is a cyclin dependent kinase 4/6 inhibitor approved for the treatment of metastatic breast cancer and is currently undergoing clinical trials for many solid tumors. Glioblastoma (GBM) is the most common primary brain tumor in adults and has limited treatment options. The cyclin-dependent kinase 4/6 pathway is commonly dysregulated in GBM and is a promising target in treating this devastating disease. The blood-brain barrier (BBB) limits the delivery of drugs to invasive regions of GBM, where the efflux transporters P-glycoprotein and breast cancer resistance protein can prevent treatments from reaching the tumor. The purpose of this study was to examine the mechanisms limiting the effectiveness of palbociclib therapy in an orthotopic xenograft model. The in vitro intracellular accumulation results demonstrated that palbociclib is a substrate for both P glycoprotein and breast cancer resistance protein. In vivo studies in transgenic mice confirmed that efflux transport is responsible for the limited brain distribution of palbociclib. There was an ~115-fold increase in brain exposure at steady state in the transporter deficient mice when compared with wild-type mice, and the efflux inhibitor elacridar significantly increased palbociclib brain distribution. Efficacy studies demonstrated that palbociclib is an effective therapy when GBM22 tumor cells are implanted in the flank, but ineffective in an orthotopic (intracranial) model. Moreover, doses designed to mimic brain exposure were ineffective in treating flank tumors. These results demonstrate that efflux transport in the BBB is involved in limiting the brain distribution of palbociclib and this has critical implications in determining effective dosing regimens of palbociclib therapy in the treatment of brain tumors. PMID- 26354994 TI - Role of u, kappa, and delta opioid receptors in tibial inhibition of bladder overactivity in cats. AB - In alpha-chloralose anesthetized cats, we examined the role of opioid receptor (OR) subtypes (u, kappa, and delta) in tibial nerve stimulation (TNS)-induced inhibition of bladder overactivity elicited by intravesical infusion of 0.25% acetic acid (AA). The sensitivity of TNS inhibition to cumulative i.v. doses of selective OR antagonists (cyprodime for u, nor-binaltorphimine for kappa, or naltrindole for delta ORs) was tested. Naloxone (1 mg/kg, i.v., an antagonist for u, kappa, and delta ORs) was administered at the end of each experiment. AA caused bladder overactivity and significantly (P < 0.01) reduced bladder capacity to 21.1% +/- 2.6% of the saline control. TNS at 2 or 4 times threshold (T) intensity for inducing toe movement significantly (P < 0.01) restored bladder capacity to 52.9% +/- 3.6% or 57.4% +/- 4.6% of control, respectively. Cyprodime (0.3-1.0 mg/kg) completely removed TNS inhibition without changing AA control capacity. Nor-binaltorphimine (3-10 mg/kg) also completely reversed TNS inhibition and significantly (P < 0.05) increased AA control capacity. Naltrindole (1-10 mg/kg) reduced (P < 0.05) TNS inhibition but significantly (P < 0.05) increased AA control capacity. Naloxone (1 mg/kg) had no effect in cyprodime pretreated cats, but it reversed the nor-binaltorphimine-induced increase in bladder capacity and eliminated the TNS inhibition remaining in naltrindole pretreated cats. These results indicate a major role of u and kappa ORs in TNS inhibition, whereas delta ORs play a minor role. Meanwhile, kappa and delta ORs also have an excitatory role in irritation-induced bladder overactivity. PMID- 26354995 TI - Loss of multidrug resistance-associated protein 1 potentiates chronic doxorubicin induced cardiac dysfunction in mice. AB - Doxorubicin (DOX), an effective cancer chemotherapeutic agent, induces dose dependent cardiotoxicity, in part due to its ability to cause oxidative stress. We investigated the role of multidrug resistance-associated protein 1 (Mrp1/Abcc1) in DOX-induced cardiotoxicity in C57BL wild-type (WT) mice and their Mrp1 null (Mrp1(-/-)) littermates. Male mice were administered intraperitoneal DOX (3 or 2 mg/kg body weight) or saline twice a week for 3 weeks and examined 2 weeks after the last dose (protocol A total dose: 18 mg/kg) or for 5 weeks, and mice were examined 48 hours and 2 weeks after the last dose (protocol B total dose: 20 mg/kg). Chronic DOX induced body weight loss and hemotoxicity, adverse effects significantly exacerbated in Mrp1(-/-) versus WT mice. In the heart, significantly higher basal levels of glutathione (1.41-fold +/- 0.27-fold) and glutathione disulfide (1.35-fold +/- 0.16-fold) were detected in Mrp1(-/-) versus WT mice, and there were comparable decreases in the glutathione/glutathione disulfide ratio in WT and Mrp1(-/-) mice after DOX administration. Surprisingly, DOX induced comparable increases in 4-hydroxynonenal glutathione conjugate concentration in hearts from WT and Mrp1(-/-) mice. However, more DOX-induced apoptosis was detected in Mrp1(-/-) versus WT hearts (P < 0.05) (protocol A), and cardiac function, assessed by measurement of fractional shortening and ejection fraction with echocardiography, was significantly decreased by DOX in Mrp1(-/-) versus WT mice (P < 0.05; 95% confidence intervals of 20.0%-24.3% versus 23.7% 29.5% for fractional shortening, and 41.5%-48.4% versus 47.7%-56.7% for ejection fraction; protocol B). Together, these data indicate that Mrp1 protects the mouse heart against chronic DOX-induced cardiotoxicity. PMID- 26354997 TI - Going beyond a First Reader: A Machine Learning Methodology for Optimizing Cost and Performance in Breast Ultrasound Diagnosis. AB - The goal of this study was to devise a machine learning methodology as a viable low-cost alternative to a second reader to help augment physicians' interpretations of breast ultrasound images in differentiating benign and malignant masses. Two independent feature sets consisting of visual features based on a radiologist's interpretation of images and computer-extracted features when used as first and second readers and combined by adaptive boosting (AdaBoost) and a pruning classifier resulted in a very high level of diagnostic performance (area under the receiver operating characteristic curve = 0.98) at a cost of pruning a fraction (20%) of the cases for further evaluation by independent methods. AdaBoost also improved the diagnostic performance of the individual human observers and increased the agreement between their analyses. Pairing AdaBoost with selective pruning is a principled methodology for achieving high diagnostic performance without the added cost of an additional reader for differentiating solid breast masses by ultrasound. PMID- 26354996 TI - Elevated glutathione is not sufficient to protect against doxorubicin-induced nuclear damage in heart in multidrug resistance-associated protein 1 (Mrp1/Abcc1) null mice. AB - Cardiotoxicity is a major dose-limiting adverse effect of doxorubicin (DOX), mediated in part by overproduction of reactive oxygen species and oxidative stress. Abcc1 (Mrp1) mediates the efflux of reduced and oxidized glutathione (GSH, GSSG) and is also a major transporter that effluxes the GSH conjugate of 4 hydroxy-2-nonenal (HNE; GS-HNE), a toxic product of lipid peroxidation formed during oxidative stress. To assess the role of Mrp1 in protecting the heart from DOX-induced cardiac injury, wild-type (WT) and Mrp1 null (Mrp1(-/-)) C57BL/6 littermate mice were administered DOX (15 mg/kg) or saline (7.5 ml/kg) i.v., and heart ventricles were examined at 72 hours. Morphometric analysis by electron microscopy revealed extensive injuries in cytosol, mitochondria, and nuclei of DOX-treated mice in both genotypes. Significantly more severely injured nuclei were observed in Mrp1(-/-) versus WT mice (P = 0.031). GSH and the GSH/GSSG ratio were significantly increased in treatment-naive Mrp1(-/-) versus WT mice; GSH remained significantly higher in Mrp1(-/-) versus WT mice after saline and DOX treatment, with no changes in GSSG or GSH/GSSG. GS-HNE, measured by mass spectrometry, was lower in the hearts of treatment-naive Mrp1(-/-) versus WT mice (P < 0.05). DOX treatment decreased GS-HNE in WT but not Mrp1(-/-) mice, so that GS-HNE was modestly but significantly higher in Mrp1(-/-) versus WT hearts after DOX. Expression of enzymes mediating GSH synthesis and antioxidant proteins did not differ between genotypes. Thus, despite elevated GSH levels in Mrp1(-/-) hearts, DOX induced significantly more injury in the nuclei of Mrp1(-/-) versus WT hearts. PMID- 26354998 TI - Public reproductive health and 'unintended' pregnancies: introducing the construct 'supportability'. AB - In this Perspectives paper, I outline the limitations of the concept of 'intentionality' in public reproductive health understandings of pregnancy. 'Intentionality', 'plannedness', 'wantedness' and 'timing' place individual cognitions, psychology and/or behaviors at the center of public health conceptualizations of pregnancies, thereby leaving the underlying social and structural dynamics under-examined. I propose a model that places 'supportability' at the center of thinking about pregnancies and that allows for an analysis of the intersection of individual cognitions, emotions and behavior with micro-level interactive spaces and macro-level issues. PMID- 26354999 TI - The availability of perifascial areolar tissue graft for deep cutaneous ulcer coverage. AB - Soft tissue defects or skin ulcers associated with tendon or bone exposure located distally on the extremities are always difficult to treat. The introduction of the vacuum-assisted closure (VAC) and dermal templates has led to major changes in ulcer treatment strategies. However, it is necessary to find an alternative method to treat these defects when VAC is not available. Perifascial areolar tissue (PAT) is the loose connective tissue on the deep fascia that could be a candidate for repairing soft tissue defects or skin ulcers. Grafting PAT on the exposed bone or tendon, including a wide coverage of well-vascularized tissue surrounding the granulation tissue, can prepare the wound to be subsequently closed by a skin graft. In this study, the PAT was used in various situations and its optimal usage and outcomes were evaluated. A total of 13 PAT grafts were performed and were especially useful for covering narrow ulcers with narrow tendon exposure and filling fistula areas. In comparison to other cases, covering the exposed cortical bone ulcers seemed to be more difficult to perform. However, an option for these ulcers could be the exposure of bone marrow and usage of intraosseous blood flow. It was also possible for the simultaneous engraftment of PAT and skin in narrow areas and could be an alternative in cases of small concave ulcers or fistulae. The PAT graft is a simple and minimally invasive procedure that can be a good alternative when VAC is not available. PMID- 26355000 TI - Measuring attentional bias in children with prominent ears: A prospective eye tracking study. AB - BACKGROUND AND AIM: When observing new faces, most people focus their attention on the central triangle of the face containing the eyes, nose and mouth. When viewing faces with prominent ears, observers may divert their attention from the central triangle. The objective of this study was to determine whether there was an objective attentional bias to prominent ears in comparison to non-prominent ears. METHODS: A total of 24 naive participants (13 female; mean age 22.88 years) viewed 15 photographs of children with bilateral prominent ears, unilateral prominent ears and non-prominent ears. Both pre- and post-otoplasty photographs of two patients were included. The eye movements of participants were recorded using the EyeLink 1000, a table-mounted eye-tracking device. RESULTS: Overall, the participants spent more time looking at the ear regions for faces with prominent ears in comparison to faces without prominent ears (p = 0.007, Z = 2.688). The attentional bias to the ear region of the patient who underwent bilateral otoplasty was significantly reduced in the post-operative photograph (p = 0.011, Z = -2.534). The patient who underwent unilateral otoplasty had no significant change in fixation times towards the ear region (p = 0.594, Z = 0.533). CONCLUSIONS: This study presents objective data to support the notion that observers show attentional bias to the ear region when viewing faces of children with prominent ears. The scope of this finding requires further research in both extent and impact. PMID- 26355001 TI - Insulin Modulates the Na+/Mg2+ Exchanger SLC41A1 and Influences Mg2+ Efflux from Intracellular Stores in Transgenic HEK293 Cells. AB - BACKGROUND: Magnesium deficiency is a common complication of diabetes with an unclear molecular background. OBJECTIVE: We investigated the effect of the insulin (INS)-signaling pathway (ISP) on the regulation of Mg(2+) efflux (Mg(2+)E) conducted by solute carrier family 41, member A1 (SLC41A1; activated by protein kinase A) in transgenic human embryonic kidney (HEK) 293 cells. METHODS: HEK293 cells overexpressing SLC41A1 were loaded with the Mg(2+) fluorescent indicator mag-fura-2 and Mg(2+). Measurements of Mg(2+)E were conducted in Mg(2+) free buffer by using fast-filter fluorescence spectrometry. We examined the effects of INS, inhibitors of ISP or p38 mitogen-activated protein kinase (p38 MAPK), an activator of adenylate cyclase (ADC), and their combinations on SLC41A1 attributed Mg(2+)E. RESULTS: The application of 400 MUU/mL INS inhibited SLC41A1 mediated Mg(2+)E by up to 50.6% compared with INS-untreated cells (P < 0.001). Moreover, INS evoked the early onset of Mg(2+) release from intracellular stores. The application of 0.1 MUM wortmannin or 10 MUM zardaverine (both ISP inhibitors) restored SLC41A1 Mg(2+)E capacity in the presence of INS to the same levels in INS-untreated cells. The simultaneous application of 10 MUM forskolin, an ADC activator, and INS resulted in a reduction of Mg(2+)E of up to 59% compared with untreated cells (P < 0.001), which was comparable to that in cells treated with INS alone. Inhibition of p38 MAPK with 10 MUM SB 202190 (SB) in the absence of INS resulted in a decrease (P < 0.001) of SLC41A1-dependent Mg(2+)E (by up to 49%) compared with Mg(2+)E measured in untreated cells. Simultaneous exposure of cells to SB and INS had a stronger inhibitory effect on SLC41A1 activity than INS alone (P < 0.05). CONCLUSIONS: INS affects intracellular Mg(2+) concentration in transgenic HEK293 cells by regulating SLC41A1 activity (via ISP) and by influencing the compartmentalization and cellular distribution of Mg(2+). In addition, p38 MAPK activates SLC41A1 independently of INS action. PMID- 26355002 TI - Amino Acid Oxidation Increases with Dietary Protein Content in Adult Neutered Male Cats as Measured Using [1-13C]Leucine and [15N2]Urea. AB - BACKGROUND: Cats are unique among domestic animals in that they are obligate carnivores and have a high protein requirement. However, there are few data on protein turnover and amino acid (AA) metabolism in cats. OBJECTIVE: The aim of this study was to examine the effects of dietary protein content on urea production and Leu metabolism in cats. METHODS: Eighteen neutered male cats (4.4 +/- 0.11 kg body weight, aged 4.6 +/- 0.41 y) fed to maintain body weight for 3 wk with 15%, 40%, or 65% metabolizable energy intake as crude protein (CP) had [1 (13)C]Leu administered in the fed state. Urea production was measured by the infusion of [(15)N2]urea. Leu flux, nonoxidative Leu disposal (NOLD; protein synthesis), Leu rate of appearance (Ra; protein degradation), and Leu oxidation were determined. RESULTS: Urea production and Leu oxidation were both ~ 3 times greater in cats fed 65% CP compared with those fed 15% CP, whereas those fed 40% CP were ~ 1.6 times greater (P < 0.05). Leu flux was 1.9 and 1.3 times greater in cats fed 65% CP compared with those fed 15% and 40% CP (P < 0.001). Almost 39% of total Leu flux was oxidized by cats fed 15% CP, whereas this increased to 58% in cats fed 65% CP (P < 0.002). There were no differences for Ra, but cats fed 65% CP tended to have 30% greater NOLD (P = 0.09) and to be in positive protein balance (P = 0.08) compared with those fed 15% CP. CONCLUSION: The high protein requirement of cats combined with a low rate of whole-body protein synthesis ensures that an obligate demand of AAs for energy or glucose (or both) can be met in an animal that evolved with a diet high in protein with very little or no carbohydrate. PMID- 26355003 TI - Dietary Macronutrient Composition Affects the Influence of Exogenous Prolactin Releasing Peptide on Appetite Responses and Hypothalamic Gene Expression in Chickens. AB - BACKGROUND: The interaction between the effects of exogenous neurotransmitters and dietary composition on appetite regulation in nonmammalian species is unclear. OBJECTIVE: The objective of this study was to determine the effects of exogenous prolactin-releasing peptide (PrRP) and dietary macronutrient composition on food intake regulation in broiler chicks. METHODS: Three isocaloric diets were formulated: high-carbohydrate (HC), high-fat (HF; 60% of ME from lard) and high-protein (HP) diets. In Expt. 1, 4-d-old Hubbard * Cobb-500 chicks fed 1 of the 3 diets since hatch were intracerebroventricularly injected with 0 (vehicle), 3, or 188 pmol PrRP (n = 10). Food intake was measured for 180 min. In Expt. 2, hypothalamic mRNA abundance of appetite-associated factors was measured in hypothalamus samples obtained 1 h postinjection of 0 or 188 pmol PrRP. In Expt. 3, chicks were given free access to all diets before and after intracerebroventricular injection and food intake was measured. RESULTS: Three and 188 pmol PrRP increased (P = 0.0008 and 0.04) HP diet intake, but only 188 pmol PrRP was efficacious at increasing HC (P = 0.0011) and HF (P = 0.01) consumption compared with the vehicle. There was a diet effect on mRNA abundance of all genes (P < 0.05), with greater expression in chicks fed the HF or HP than the HC diet. Whereas neuropeptide Y (NPY) mRNA was similar between vehicle- and PrRP-injected chicks that consumed HP or HF diets, expression was greater (P < 0.05) in PrRP- than vehicle-injected chicks that consumed the HC diet. When chicks had access to all diets, 188 pmol PrRP caused preferential (P < 0.0001) intake of the HP over the HC and HF diets. CONCLUSION: The HP diet enhanced the sensitivity of chicks to the food intake-stimulating effects of PrRP, and PrRP in turn increased preference for the HP diet. Thus, dietary macronutrient composition influences PrRP-mediated food intake, and PrRP in turn affects nutrient intake and transcriptional regulation in chicks. PMID- 26355004 TI - CETCh-seq: CRISPR epitope tagging ChIP-seq of DNA-binding proteins. AB - Chromatin immunoprecipitation followed by next-generation DNA sequencing (ChIP seq) is a widely used technique for identifying transcription factor (TF) binding events throughout an entire genome. However, ChIP-seq is limited by the availability of suitable ChIP-seq grade antibodies, and the vast majority of commercially available antibodies fail to generate usable data sets. To ameliorate these technical obstacles, we present a robust methodological approach for performing ChIP-seq through epitope tagging of endogenous TFs. We used clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-based genome editing technology to develop CRISPR epitope tagging ChIP-seq (CETCh-seq) of DNA-binding proteins. We assessed the feasibility of CETCh-seq by tagging several DNA-binding proteins spanning a wide range of endogenous expression levels in the hepatocellular carcinoma cell line HepG2. Our data exhibit strong correlations between both replicate types as well as with standard ChIP-seq approaches that use TF antibodies. Notably, we also observed minimal changes to the cellular transcriptome and to the expression of the tagged TF. To examine the robustness of our technique, we further performed CETCh-seq in the breast adenocarcinoma cell line MCF7 as well as mouse embryonic stem cells and observed similarly high correlations. Collectively, these data highlight the applicability of CETCh-seq to accurately define the genome-wide binding profiles of DNA-binding proteins, allowing for a straightforward methodology to potentially assay the complete repertoire of TFs, including the large fraction for which ChIP-quality antibodies are not available. PMID- 26355005 TI - Linked selection and recombination rate variation drive the evolution of the genomic landscape of differentiation across the speciation continuum of Ficedula flycatchers. AB - Speciation is a continuous process during which genetic changes gradually accumulate in the genomes of diverging species. Recent studies have documented highly heterogeneous differentiation landscapes, with distinct regions of elevated differentiation ("differentiation islands") widespread across genomes. However, it remains unclear which processes drive the evolution of differentiation islands; how the differentiation landscape evolves as speciation advances; and ultimately, how differentiation islands are related to speciation. Here, we addressed these questions based on population genetic analyses of 200 resequenced genomes from 10 populations of four Ficedula flycatcher sister species. We show that a heterogeneous differentiation landscape starts emerging among populations within species, and differentiation islands evolve recurrently in the very same genomic regions among independent lineages. Contrary to expectations from models that interpret differentiation islands as genomic regions involved in reproductive isolation that are shielded from gene flow, patterns of sequence divergence (d(xy) and relative node depth) do not support a major role of gene flow in the evolution of the differentiation landscape in these species. Instead, as predicted by models of linked selection, genome-wide variation in diversity and differentiation can be explained by variation in recombination rate and the density of targets for selection. We thus conclude that the heterogeneous landscape of differentiation in Ficedula flycatchers evolves mainly as the result of background selection and selective sweeps in genomic regions of low recombination. Our results emphasize the necessity of incorporating linked selection as a null model to identify genome regions involved in adaptation and speciation. PMID- 26355006 TI - Noise in gene expression is coupled to growth rate. AB - Genetically identical cells exposed to the same environment display variability in gene expression (noise), with important consequences for the fidelity of cellular regulation and biological function. Although population average gene expression is tightly coupled to growth rate, the effects of changes in environmental conditions on expression variability are not known. Here, we measure the single-cell expression distributions of approximately 900 Saccharomyces cerevisiae promoters across four environmental conditions using flow cytometry, and find that gene expression noise is tightly coupled to the environment and is generally higher at lower growth rates. Nutrient-poor conditions, which support lower growth rates, display elevated levels of noise for most promoters, regardless of their specific expression values. We present a simple model of noise in expression that results from having an asynchronous population, with cells at different cell-cycle stages, and with different partitioning of the cells between the stages at different growth rates. This model predicts non-monotonic global changes in noise at different growth rates as well as overall higher variability in expression for cell-cycle-regulated genes in all conditions. The consistency between this model and our data, as well as with noise measurements of cells growing in a chemostat at well-defined growth rates, suggests that cell-cycle heterogeneity is a major contributor to gene expression noise. Finally, we identify gene and promoter features that play a role in gene expression noise across conditions. Our results show the existence of growth-related global changes in gene expression noise and suggest their potential phenotypic implications. PMID- 26355007 TI - Sexual health provision in Defence Primary Health Care: a model for change? AB - INTRODUCTION: Defence Primary Health Care (DPHC) as an organisation has the responsibility for the provision of a basic level of sexual health service that every patient can access, regardless of their geographical location. The Military Advice and Sexual Health/HIV service (MASHH), based in Birmingham, provides nationally validated sexual health training and accreditation. Training was delivered to an isolated DPHC region to allow as many doctors and nurses to attend and minimised associated travel and accommodation costs. This training initiative enabled military personnel to access sexual health services within their own medical centres and reduced the number of potential referrals to local services. To assess compliance with the relevant standards, MASHH audited the DPHC region 2 months following completion of training. This was to ensure that the level 1 sexual health service provided by the DPHC region met with current British Association of Sexual Health and HIV (BASHH) Standards. METHODS: Provision of sexual health services in the four medical centres in the DPHC region were assessed for a 6-month period against the standards set by BASHH. RESULTS: Few of the audit standards were met; this was in part due to personnel undertaking sexual health consultations who had not been appropriately trained and partly due to unrecognised deficiencies in the DPHC computer coding systems. CONCLUSIONS: Overall, this programme demonstrates a potential model for the cost effective roll-out of accredited sexual health training and resultant service provision for other DPHC regions, but some changes are needed to ensure national standards are met. PMID- 26355009 TI - Hyperglycaemia in pregnancy: still a lot to learn. PMID- 26355008 TI - Cardiovascular and neuropsychiatric risks of varenicline: a retrospective cohort study. AB - BACKGROUND: Varenicline is an effective pharmacotherapy to aid smoking cessation. However, its use is limited by continuing concerns about possible associated risks of serious adverse cardiovascular and neuropsychiatric events. The aim of this study was to investigate whether use of varenicline is associated with such events. METHODS: In this retrospective cohort study, we used data from patients included in the validated QResearch database, which holds data from 753 National Health Service general practices across England. We identified patients aged 18 100 years (registered for longer than 12 months before data extraction) who received a prescription of nicotine replacement treatment (NRT; reference group), bupropion, or varenicline. We excluded patients if they had used one of the drugs during the 12 months before the start date of the study, had received a prescription of a combination of these drugs during the follow-up period, or were temporary residents. We followed patients up for 6 months to compare incident cardiovascular (ischaemic heart disease, cerebral infarction, heart failure, peripheral vascular disease, and cardiac arrhythmia) and neuropsychiatric (depression and self-harm) events using Cox proportional hazards models, adjusted for potential confounders (primary outcomes). FINDINGS: We identified 164,766 patients who received a prescription (106,759 for nicotine replacement treatment; 6557 for bupropion; 51,450 for varenicline) between Jan 1, 2007, and June 30, 2012. Neither bupropion nor varenicline showed an increased risk of any cardiovascular or neuropsychiatric event compared with NRT (all hazard ratios [HRs] less than 1. Varenicline was associated with a significantly reduced risk of ischaemic heart disease (HR 0.80 [95%CI 0.72-0.87]), cerebral infarction (0.62 [0.52-0.73]), heart failure (0.61 [0.45-0.83]), arrhythmia (0.73 [0.60-0.88]), depression (0.66 [0.63-0.69]), and self-harm (0.56 [0.46-0.68]). INTERPRETATION: Varenicline does not seem to be associated with an increased risk of documented cardiovascular events, depression, or self-harm when compared with NRT. Adverse events that do not come to attention of general practitioners cannot be excluded. These findings suggest an opportunity for physicians to prescribe varenicline more broadly, even for patients with comorbidities, thereby helping more smokers to quit successfully than do at present. FUNDING: Egton Medical Information Systems, University of Nottingham, Ministry of Innovation, Science and Research of the German Federal State of North Rhine-Westphalia, Cancer Research UK, Medical Research Council, Commonwealth Fund. PMID- 26355010 TI - Association between hyperglycaemia and adverse perinatal outcomes in south Asian and white British women: analysis of data from the Born in Bradford cohort. AB - BACKGROUND: Diagnosis of gestational diabetes predicts risk of infants who are large for gestational age (LGA) and with high adiposity, which in turn aims to predict a future risk of obesity in the offspring. South Asian women have higher risk of gestational diabetes, lower risk of LGA, and on average give birth to infants with greater adiposity than do white European women. Whether the same diagnostic criteria for gestational diabetes should apply to both groups of women is unclear. We aimed to assess the association between maternal glucose and adverse perinatal outcomes to ascertain whether thresholds used to diagnose gestational diabetes should differ between south Asian and white British women. We also aimed to assess whether ethnic origin affected prevalence of gestational diabetes irrespective of criteria used. METHODS: We used data (including results of a 26-28 week gestation oral glucose tolerance test) of women from the Born in Bradford study, a prospective study that recruited women attending the antenatal clinic at the Bradford Royal Infirmary, UK, between 2007 and 2011 and who intended to give birth to their infant in that hospital. We studied the association between fasting and 2 h post-load glucose and three primary outcomes (LGA [defined as birthweight >90th percentile for gestational age], high infant adiposity [sum of skinfolds >90th percentile for gestational age], and caesarean section). We calculated adjusted odds ratios (ORs) and their 95% confidence intervals (CIs) for a 1 SD increase in fasting and post-load glucose. We established fasting and post-load glucose thresholds that equated to an OR of 1.75 for LGA and high infant adiposity in each group of women to identify ethnic specific criteria for diagnosis of gestational diabetes. FINDINGS: Of 13,773 pregnancies, 3420 were excluded from analyses. Of 10,353 eligible pregnancies, 4088 women were white British, 5408 were south Asian, and 857 were of other ethnic origin. The adjusted ORs of LGA per 1 SD fasting glucose were 1.22 (95% CI 1.08-1.38) in white British women and 1.43 (1.23-1.67) in south Asian women (pinteraction with ethnicity = 0.39). Results for high infant adiposity were 1.35 (1.23-1.49) and 1.35 (1.18-1.54; pinteraction with ethnicity=0.98), and for caesarean section they were 1.06 (0.97-1.16) and 1.11 (1.02-1.20; pinteraction with ethnicity=0.47). Associations between post-load glucose and the three primary outcomes were weaker than for fasting glucose. A fasting glucose concentration of 5.4 mmol/L or a 2 h post-load level of 7.5 mmol/L identified white British women with 75% or higher relative risk of LGA or high infant adiposity; in south Asian women, the cutoffs were 5.2 mmol/L or 7.2 mml/L; in the whole cohort, the cutoffs were 5.3 mmol/L or 7.5 mml/L. The prevalence of gestational diabetes in our cohort ranged from 1.2% to 8.7% in white British women and 4% to 24% in south Asian women using six different criteria. Compared with the application of our whole-cohort criteria, use of our ethnic-specific criteria increased the prevalence of gestational diabetes in south Asian women from 17.4% (95% CI 16.4-18.4) to 24.2% (23.1-25.3). INTERPRETATION: Our data support the use of lower fasting and post-load glucose thresholds to diagnose gestational diabetes in south Asian than white British women. They also suggest that diagnostic criteria for gestational diabetes recommended by UK NICE might underestimate the prevalence of gestational diabetes compared with our criteria or those recommended by the International Association of Diabetes and Pregnancy Study Groups and WHO, especially in south Asian women. FUNDING: The National Institute for Health Research. PMID- 26355012 TI - Facile formation of mesoporous BiVO4/Ag/AgCl heterostructured microspheres with enhanced visible-light photoactivity. AB - In this study, we demonstrate a facile and novel dual-ion-exchange method together with subsequent visible-light induced reduction for synthesis of mesoporous BiVO4/Ag/AgCl ternary heterostructured microspheres (HSMSs) with uniform size distribution. Using flower-like BiOCl microspheres as the starting material, and introducing NaVO3 and AgNO3 by a facile impregnation method, mesoporous BiVO4/AgCl HSMSs have been obtained through solid-phase dual-ion exchange reactions at 400 degrees C for 2 h. Interestingly, it has been found that Ag(+) ions play an indispensable role on the dual-ion-exchange reactions, and then the BiVO4/AgCl HSMSs are converted into BiVO4/Ag/AgCl ternary HSMSs by a facile visible-light illumination for 2 h. The as-prepared mesoporous BiVO4/Ag/AgCl ternary HSMSs manifest high photocatalytic activity in degrading methyl orange (MO) and phenol under visible-light illumination, and a possible Z scheme photocatalytic mechanism is proposed to understand the enhanced photochemical properties. PMID- 26355011 TI - The Greater Phenotypic Homeostasis of the Allopolyploid Coffea arabica Improved the Transcriptional Homeostasis Over that of Both Diploid Parents. AB - Polyploidy impacts the diversity of plant species, giving rise to novel phenotypes and leading to ecological diversification. In order to observe adaptive and evolutionary capacities of polyploids, we compared the growth, primary metabolism and transcriptomic expression level in the leaves of the newly formed allotetraploid Coffea arabica species compared with its two diploid parental species (Coffea eugenioides and Coffea canephora), exposed to four thermal regimes (TRs; 18-14, 23-19, 28-24 and 33-29 degrees C). The growth rate of the allopolyploid C. arabica was similar to that of C. canephora under the hottest TR and that of C. eugenioides under the coldest TR. For metabolite contents measured at the hottest TR, the allopolyploid showed similar behavior to C. canephora, the parent which tolerates higher growth temperatures in the natural environment. However, at the coldest TR, the allopolyploid displayed higher sucrose, raffinose and ABA contents than those of its two parents and similar linolenic acid leaf composition and Chl content to those of C. eugenioides. At the gene expression level, few differences between the allopolyploid and its parents were observed for studied genes linked to photosynthesis, respiration and the circadian clock, whereas genes linked to redox activity showed a greater capacity of the allopolyploid for homeostasis. Finally, we found that the overall transcriptional response to TRs of the allopolyploid was more homeostatic compared with its parents. This better transcriptional homeostasis of the allopolyploid C. arabica afforded a greater phenotypic homeostasis when faced with environments that are unsuited to the diploid parental species. PMID- 26355013 TI - [Spinal injection of local anesthetic during cervical facet joint injection]. AB - INTRODUCTION: Facet joint pain is a common source of non-radicular back pain worldwide. Non-surgical interventional modalities remain the mainstay in the treatment of facetogenic back pain and comprise the second most commonly performed interventional pain procedures in the USA. CASE: A 36 year-old man with chronic cervical pain secondary to C6-C7 facet arthrosis radiographically, underwent diagnostic local anesthetic bilateral facet joint injection under fluoroscopic guidance. The left side was injected uneventfully; however, 1-2min following injection of the right side the patient complained of unwellness and became very anxious. He referred paresthesias of the bilateral upper extremities, chest and upper abdomen. Physical examination showed sensory deficits roughly from C5 to T7 without motor deficits; resuscitation measures were not warranted. The deficits were completely resolved by 35-40min in the recovery area. DISCUSSION: Facet joint injections are a common and safe method of treating back pain secondary to facet arthropathy. Despite excellent safety profiles, rare and sometimes, life-threatening complications can occur. Our case hypothesizes intrathecal injection of local anesthetic during facet joint injection. Few reports have described similar situations. We hypothesize a mechanism of entry through the facet joint, given the proximity of the ligamentum flavum, and the intrathecal space to the anterior aspect of the facet joint. This report reinforces the need for resuscitation and airway management equipment to be readily available where interventional procedures are performed, as well as the need for adequate proficiency in airway management and resuscitation techniques in Pain Medicine training. PMID- 26355014 TI - Attenuation of the progression of articular cartilage degeneration by inhibition of TGF-beta1 signaling in a mouse model of osteoarthritis. AB - Transforming growth factor beta 1 (TGF-beta1) is implicated in osteoarthritis. We therefore studied the role of TGF-beta1 signaling in the development of osteoarthritis in a developmental stage-dependent manner. Three different mouse models were investigated. First, the Tgf-beta receptor II (Tgfbr2) was specifically removed from the mature cartilage of joints. Tgfbr2-deficient mice were grown to 12 months of age and were then euthanized for collection of knee and temporomandibular joints. Second, Tgfbr2-deficient mice were subjected to destabilization of the medial meniscus (DMM) surgery. Knee joints were then collected from the mice at 8 and 16 weeks after the surgery. Third, wild-type mice were subjected to DMM at the age of 8 weeks. Immediately after the surgery, these mice were treated with the Tgfbr2 inhibitor losartan for 8 weeks and then euthanized for collection of knee joints. All joints were characterized for evidences of articular cartilage degeneration. Initiation or acceleration of articular cartilage degeneration was not observed by the genetic inactivation of Tgfbr2 in the joints at the age of 12 months. In fact, the removal of Tgfbr2 and treatment with losartan both delayed the progression of articular cartilage degeneration induced by DMM compared with control littermates. Therefore, we conclude that inhibition of Tgf-beta1 signaling protects adult knee joints in mice against the development of osteoarthritis. PMID- 26355015 TI - A Genetic Network Associated With Stress Resistance, Longevity, and Cancer in Humans. AB - Human longevity and diseases are likely influenced by multiple interacting genes within a few biologically conserved pathways. Using long-lived smokers as a phenotype (n = 90)-a group whose survival may signify innate resilience-we conducted a genome-wide association study comparing them to smokers at ages 52-69 (n = 730). These results were used to conduct a functional interaction network and pathway analysis, to identify single nucleotide polymorphisms that collectively related to smokers' longevity. We identified a set of 215 single nucleotide polymorphisms (all of which had p <5*10(-3) in the genome-wide association study) that were located within genes making-up a functional interaction network. These single nucleotide polymorphisms were then used to create a weighted polygenic risk score that, using an independent validation sample of nonsmokers (N = 6,447), was found to be significantly associated with a 22% increase in the likelihood of being aged 90-99 (n = 253) and an over threefold increase in the likelihood of being a centenarian (n = 4), compared with being at ages 52-79 (n = 4,900). Additionally, the polygenic risk score was also associated with an 11% reduction in cancer prevalence over up to 18 years (odds ratio: 0.89, p = .011). Overall, using a unique phenotype and incorporating prior knowledge of biological networks, this study identified a set of single nucleotide polymorphisms that together appear to be important for human aging, stress resistance, cancer, and longevity. PMID- 26355016 TI - Risk of Frailty in Elderly With COPD: A Population-Based Study. AB - BACKGROUND: Despite frailty being an important geriatric syndrome, its prevalence and associated mortality risk in older patients with chronic obstructive pulmonary disease (COPD) are unknown. METHODS: We examined the relationship between COPD confirmed by spirometry, COPD severity, and frailty defined by the Fried criteria within 2,142 participants (aged 74.7 +/- 5.6 years) of the Rotterdam Study, a prospective population-based cohort study. RESULTS: The frailty prevalence was significantly higher (p < .001) in participants with COPD (10.2%, 95% CI: 7.6%-13.5%) compared with participants without COPD (3.4%, 95% CI: 2.6%-4.4%). Adjusted for age, sex, smoking, corticosteroids, and other confounders, participants with COPD had a more than twofold increased prevalence of frailty (odds ratio 2.2, 95% CI: 1.34-3.54, p = .002). The prevalence was highest when severe airflow limitation, dyspnea, and frequent exacerbations were present. Participants with mild airflow limitation were more frequently prefrail. COPD elderly who were frail had significant worse survival. CONCLUSIONS: This population-based cohort study in elderly demonstrates that COPD is associated with frailty even after adjusting for shared risk factors. Our findings suggest that frailty-in addition to COPD severity and comorbidities-identifies those COPD participants at high risk of mortality. PMID- 26355018 TI - Gadofosveset trisodium-enhanced MR angiography for detection of lower gastrointestinal bleeding. AB - The purpose of our study is to determine if Gadofosveset trisodium-enhanced magnetic resonance angiography (MRA) could be used for detection and localization of acute lower gastrointestinal (LGI) bleed. Four patients underwent MRA (4 females, mean age of 65 years) for suspected LGI bleeding. MRA detected an active rectal bleed in one patient. All other patients did not demonstrate active bleeding and these true negatives were confirmed by computed tomography angiography, endoscopy, and tagged-red blood cell scan or digital subtraction angiography. Preliminary results suggest that MRA may serve as an alternative technique for detecting acute LGI bleeding when nuclear scintigraphy is unavailable or in the younger radiosensitive population but further investigation in a larger cohort is required. PMID- 26355017 TI - Change in Epigenome-Wide DNA Methylation Over 9 Years and Subsequent Mortality: Results From the InCHIANTI Study. AB - Patterns of DNA methylation (DNAm) that track with aging have been identified. However, the relevance of these patterns for aging outcomes remains unclear. Longitudinal epigenome-wide DNAm information was obtained from the InCHIANTI study, a large representative European population. DNAm was evaluated using the Illumina HumanMethylation450 array on blood samples collected at baseline and 9 year follow-up: observations from 499 participants with paired longitudinal blood sample and information on differential blood count were included in analyses. A total of 56,579 markers were significantly associated with age in cross-sectional analysis of DNAm at year 9, 31,252 markers were changed significantly over the 9 year follow-up, and 16,987 markers were both cross-sectionally associated with age and significantly changed over time. Rates of change at 76 markers and year 9 level of DNAm at 88 markers were identified as strongly associated with mortality in Cox proportional hazard models adjusted for age and relevant covariates (mean follow-up time 4.4 years). Less than 0.05% of markers associated with age or that changed over time were also associated with mortality after adjusting for chronological age. Although the influence of DNAm on health and longevity remains unclear, these findings confirm that aging is associated cross-sectionally and longitudinally with robust and consistent patterns of methylation change. PMID- 26355019 TI - Dietary cocoa inhibits colitis associated cancer: a crucial involvement of the IL 6/STAT3 pathway. AB - Patients with inflammatory bowel disease (IBD) are at increased risk for developing ulcerative colitis-associated colorectal cancer (CRC). The interleukin 6 (IL-6)/signal transducer and activator of transcription (STAT)-3 signaling regulates survival and proliferation of intestinal epithelial cells and play an important role in the pathogenesis of IBD and CRC. Cocoa is enriched with polyphenols that known to possess antioxidant, anti-inflammatory and antitumor activities. Here, we explored the antitumor effects and mechanisms of cocoa diet on colitis-associated cancer (CAC) using the azoxymethane/dextran sulfate sodium model, with a particular focus on whether cocoa exerts its anticancer effect through the IL-6/STAT3 pathway. We found that cocoa significantly decreased the tumor incidence and size in CAC-induced mice. In addition to inhibiting proliferation of tumor epithelial cells, cocoa suppressed colonic IL-6 expression and subsequently activation of STAT3. Thus, our findings demonstrated that cocoa diet suppresses CAC tumorigenesis, and its antitumor effect is partly mediated by limiting IL-6/STAT3 activation. In addition, cocoa induces apoptosis by increased the expressions of Bax and caspase 3 and decreased Bcl-xl. Thus, we conclude that cocoa may be a potential agent in the prevention and treatment of CAC. PMID- 26355021 TI - Mechanical ventilation in critically-ill pregnant women: a case series. AB - BACKGROUND: Approximately 0.1-0.2% of pregnancies are complicated by respiratory failure requiring mechanical ventilatory support, but few data exist to inform clinical management. This study aimed to characterize current practice and the effect of delivery on respiratory function. METHODS: A retrospective review was performed of pregnant women who received mechanical ventilation for more than 24h, from four intensive care units in institutions with large-volume obstetric units. RESULTS: Data were collected from 29 patients with a mean gestation at intensive care unit admission of 25.3 +/- 6 weeks. Tidal volumes were 7.7 +/- 1.7 mL/kg predicted body weight. Estimated respiratory system compliance was reduced, but was higher in four patients ventilated for neurological conditions without lung disease. Three maternal and three neonatal deaths occurred. Ten patients delivered while on ventilatory support: one spontaneous delivery, four for obstetric indications and five for worsening maternal condition. Following delivery of these 10 patients, three demonstrated a greater than 50% decrease in oxygenation index and five a greater than 50% increase in compliance. No characteristics identified which patients may benefit from delivery. CONCLUSIONS: Review of current practice in four centers suggests that mechanical ventilation in pregnant patients follows usual guidelines applicable to non-pregnant patients. Delivery was associated with modest improvement in maternal respiratory function in some patients. Any potential benefit of delivery in improving maternal physiology must be weighed against the stress of delivery. The risks of premature birth for the fetus must be weighed against continued exposure to maternal hypoxemia and hypotension. PMID- 26355022 TI - Analytic Strategies and Sample Size. PMID- 26355020 TI - Ultra-High Density, Transcript-Based Genetic Maps of Pepper Define Recombination in the Genome and Synteny Among Related Species. AB - Our ability to assemble complex genomes and construct ultradense genetic maps now allows the determination of recombination rates, translocations, and the extent of genomic collinearity between populations, species, and genera. We developed two ultradense genetic linkage maps for pepper from single-position polymorphisms (SPPs) identified de novo with a 30,173 unigene pepper genotyping array. The Capsicum frutescens * C. annuum interspecific and the C. annuum intraspecific genetic maps were constructed comprising 16,167 and 3,878 unigene markers in 2108 and 783 genetic bins, respectively. Accuracies of marker groupings and orders are validated by the high degree of collinearity between the two maps. Marker density was sufficient to locate the chromosomal breakpoint resulting in the P1/P8 translocation between C. frutescens and C. annuum to a single bin. The two maps aligned to the pepper genome showed varying marker density along the chromosomes. There were extensive chromosomal regions with suppressed recombination and reduced intraspecific marker density. These regions corresponded to the pronounced nonrecombining pericentromeric regions in tomato, a related Solanaceous species. Similar to tomato, the extent of reduced recombination appears to be more pronounced in pepper than in other plant species. Alignment of maps with the tomato and potato genomes shows the presence of previously known translocations and a translocation event that was not observed in previous genetic maps of pepper. PMID- 26355023 TI - Mandibular reconstructions using computer-aided design/computer-aided manufacturing: A systematic review of a defect-based reconstructive algorithm. AB - Modern planning techniques, including computer-aided design/computer-aided manufacturing (CAD-CAM) can be used to plan reconstructive surgery, optimising aesthetic outcomes and functional rehabilitation. However, although many such applications are available, no systematic protocol yet describes the entire reconstructive procedure, which must include virtual planning, custom manufacture, and a reconstructive algorithm. We reviewed current practices in this novel field, analysed case series described in the literature, and developed a new, defect-based reconstructive algorithm. We also evaluated methods of mandibular reconstruction featuring virtual planning, the use of surgical guides, and laser printing of custom titanium bony plates to support composite free flaps, and evaluated their utility. PMID- 26355024 TI - Perioperative discontinuation of intravenous bisphosphonate therapy reduces the incidence and severity of bisphosphonate-related osteonecrosis of the jaw: A randomized, controlled, prospective experimental study in rats. AB - OBJECTIVE: To evaluate the effects of intravenous bisphosphonate discontinuation on incidence and severity of bisphosphonate-related osteonecrosis of the jaw (BRONJ). MATERIAL AND METHODS: Seventy rats were randomly divided into 7 groups. In control and S0 groups, weekly injection of saline and 0.06 mg/kg zoledronate (respectively) for 4 weeks, tooth extraction, continuation of injections for 2 months and euthanasia were performed. In group S1, zolendronate injection for 4 weeks, tooth extraction, zolendronate discontinuation for 2 months, and euthanasia were done. For groups S2, S3, S4, and S5, zolendronate injections for 4 weeks, drug holiday for 1-4 months (respectively) before and 2 months after tooth extraction, and euthanasia were performed. Presence of bone exposure, osteonecrosis, and new bone formation were clinically and histologically evaluated. RESULTS: The rate of BRONJ in control, S0, S1, S2, S3, S4, and S5 groups was 0%, 85%, 80%, 65%, 60%, 50%, and 40%, respectively. In control group, epithelial healing, bone formation, and absence of osteonecrosis; and in S0 group, unhealed epithelium, osteonecrosis, and impaired bone formation were histologically observed. In study groups, prolongation of drug holiday caused diminished osteonecrosis, and improved bone and epithelial healing. CONCLUSION: Zolendronate discontinuation significantly decreased the incidence and severity of BRONJ in rats. PMID- 26355025 TI - Surface-optimized free flaps for complex facial defects after skin cancer. AB - INTRODUCTION: Advanced non-melanocytic skin cancer (NMSC) in the facial region causes extensive tissue loss, possibly coverable by local flaps. Remote free flaps are the reconstructive method of choice, despite disadvantages such as color and texture mismatch, and bulkiness with regard to facial skin. MATERIAL AND METHODS: Post-ablative facial NMSC defects in four patients were reconstructed using remote free flaps, including radial forearm, scapular, parascapular, and anterolateral thigh flaps. Four months later, a split-thickness skin graft (STSG) was acquired from the retroauricular region to generate a non cultured autologous epidermal cell (NCAEC) suspension. The flap surfaces were de epithelialized, and the NCAEC suspension was sprayed onto the flap surface to improve the mismatch between facial and flap color. Debulking was also carried out. The aesthetic outcome was examined by photography and clinical examination 3, 6, 9, and 12 months after the first operation. RESULTS: All flaps survived the 11- to 21-month follow-up. The secondary operation was accompanied by a delay in re-epithelialization in one case. No STSG donor-site problems occurred. Follow-up photographs showed significant improvements in the color and texture of the flaps. CONCLUSIONS: Facial reconstruction with a free flap results in a mismatch of color and texture. Secondary correction of the flap surface by de epithelialization and NCAEC application significantly improves the aesthetic outcome. PMID- 26355026 TI - Clinical efficacy of different doses of lipo-prostaglandin E1 in the treatment of painful diabetic peripheral neuropathy. AB - OBJECTIVE: To observe the clinical efficacy of different doses of alprostadil (lipo-prostaglandin E1, lipo-PGE1) in the treatment of painful diabetic peripheral neuropathy (DPN). METHODS: Sixty patients with painful DPN were equally and randomly assigned into three groups. Two groups received different doses of lipo-PGE1 by intravenous drip injection (A group: low-dose lipo-PGE1; B group: high-dose lipo-PGE1) following intravenous bolus injection of mecobalamin (MeCbl, 0.5mg once daily (QD)); the third group received MeCbl alone (C group). All patients received optimized treatment to lower blood glucose, blood pressure, and blood lipids to target levels. The efficacy of lipo-PGE1 in the three groups of patients was observed after 3weeks of treatment. RESULTS: The overall response rate was 90% in the B group, significantly higher than that in the A and C groups (80% and 55%, respectively; P<0.05). During the observation period, there was no incidence of serious adverse reactions (e.g., acute heart failure, sudden drop in blood pressure, or malignant arrhythmias) in any of the three groups. CONCLUSIONS: High-dose lipo-PGE1 has better efficacy than low-dose lipo-PGE1 or MeCbl alone in the treatment of painful DPN. PMID- 26355027 TI - The impact of hyperglycemia and obesity on hospitalization costs and clinical outcome in general surgery patients. AB - BACKGROUND: The impact of obesity on clinical outcomes and hospitalization costs in general surgery patients with and without diabetes (DM) is unknown. MATERIALS AND METHODS: We reviewed medical records of 2451 patients who underwent gastrointestinal surgery at two university hospitals. Hyperglycemia was defined as BG >=140 mg/dl. Overweight was defined by body mass index (BMI) between 25 29.9 kg/m(2) and obesity as a BMI >=30 kg/m(2). Hospital cost was calculated using cost-charge ratios from Centers for Medicare and Medicaid Services. Hospital complications included a composite of major cardiovascular events, pneumonia, bacteremia, acute kidney injury (AKI), respiratory failure, and death. RESULTS: Hyperglycemia was present in 1575 patients (74.8%). Compared to patients with normoglycemia, those with DM and non-DM with hyperglycemia had higher number of complications (8.9% vs. 35.8% vs. 30.0%, p<0.0001), longer hospital stay (5 days vs. 9 days vs. 9 days, p<0.0001), more readmissions within 30 days (9.3% vs. 18.8% vs. 17.2%, p<0.0001), and higher hospitalization costs ($20,273 vs. $79,545 vs. $72,675, p<0.0001). In contrast, compared to normal-weight subjects, overweight and obesity were not associated with increased hospitalization costs ($58,313 vs. $58,173 vs. $66,633, p=0.74) or risk of complications, except for AKI (11.9% vs. 14.8% vs. 20.5%, p<0.0001). Multivariate analysis revealed that DM (OR=4.4, 95% CI=2.8,7.0) or perioperative hyperglycemia (OR=4.1, 95% CI=2.7-6.2) were independently associated with increased risk of complications. CONCLUSION: Hyperglycemia but not increasing BMI, in patients with and without diabetes undergoing gastrointestinal surgery was associated with a higher number of complications and hospitalization costs. PMID- 26355028 TI - NS1: A corner piece in the dengue pathogenesis puzzle? AB - Soluble dengue virus NS1 protein induces proinflammatory immune responses via Toll-like receptor 4 and disrupts endothelial cell integrity, resulting in vascular leakage (Beatty et al. and Modhiran et al., this issue). PMID- 26355029 TI - Hurdles in therapy with regulatory T cells. AB - Improper activation of the immune system contributes to a variety of clinical conditions, including autoimmune and allergic diseases as well as solid organ and bone marrow transplantation. One approach to counteract this activation is through adoptive therapy with regulatory T cells (Tregs). Efforts to manufacture these cells have led to good maunfacturing practice-compliant protocols, and Treg products are entering early clinical trials. Here, we report the stance of the European Union Cooperation in Science and Technology Action BM1305, "Action to Focus and Accelerate Cell-based Tolerance-inducing Therapies-A FACTT," which identifies hurdles hindering Treg clinical applications in Europe and provides possible solutions. PMID- 26355030 TI - Dengue virus NS1 triggers endothelial permeability and vascular leak that is prevented by NS1 vaccination. AB - The four dengue virus serotypes (DENV1 to DENV4) are mosquito-borne flaviviruses that cause up to ~100 million cases of dengue annually worldwide. Severe disease is thought to result from immunopathogenic processes involving serotype cross reactive antibodies and T cells that together induce vasoactive cytokines, causing vascular leakage that leads to shock. However, no viral proteins have been directly implicated in triggering endothelial permeability, which results in vascular leakage. DENV nonstructural protein 1 (NS1) is secreted and circulates in patients' blood during acute infection; high levels of NS1 are associated with severe disease. We show that inoculation of mice with DENV NS1 alone induces both vascular leakage and production of key inflammatory cytokines. Furthermore, simultaneous administration of NS1 with a sublethal dose of DENV2 results in a lethal vascular leak syndrome. We also demonstrate that NS1 from DENV1, DENV2, DENV3, and DENV4 triggers endothelial barrier dysfunction, causing increased permeability of human endothelial cell monolayers in vitro. These pathogenic effects of physiologically relevant amounts of NS1 in vivo and in vitro were blocked by NS1-immune polyclonal mouse serum or monoclonal antibodies to NS1, and immunization of mice with NS1 from DENV1 to DENV4 protected against lethal DENV2 challenge. These findings add an important and previously overlooked component to the causes of dengue vascular leak, identify a new potential target for dengue therapeutics, and support inclusion of NS1 in dengue vaccines. PMID- 26355031 TI - Dengue virus NS1 protein activates cells via Toll-like receptor 4 and disrupts endothelial cell monolayer integrity. AB - Complications arising from dengue virus infection include potentially fatal vascular leak, and severe disease has been linked with excessive immune cell activation. An understanding of the triggers of this activation is critical for the development of appropriately targeted disease control strategies. We show here that the secreted form of the dengue virus nonstructural protein 1 (NS1) is a pathogen-associated molecular pattern (PAMP). Highly purified NS1 devoid of bacterial endotoxin activity directly activated mouse macrophages and human peripheral blood mononuclear cells (PBMCs) via Toll-like receptor 4 (TLR4), leading to the induction and release of proinflammatory cytokines and chemokines. In an in vitro model of vascular leak, treatment with NS1 alone resulted in the disruption of endothelial cell monolayer integrity. Both NS1-mediated activation of PBMCs and NS1-induced vascular leak in vitro were inhibited by a TLR4 antagonist and by anti-TLR4 antibody treatment. The importance of TLR4 activation in vivo was confirmed by the reduction in capillary leak by a TLR4 antagonist in a mouse model of dengue virus infection. These results pinpoint NS1 as a viral toxin counterpart of the bacterial endotoxin lipopolysaccharide (LPS). Similar to the role of LPS in septic shock, NS1 might contribute to vascular leak in dengue patients, which highlights TLR4 antagonists as a possible therapeutic option. PMID- 26355032 TI - The mitotic kinesin KIF11 is a driver of invasion, proliferation, and self renewal in glioblastoma. AB - The proliferative and invasive nature of malignant cancers drives lethality. In glioblastoma, these two processes are presumed mutually exclusive and hence termed "go or grow." We identified a molecular target that shuttles between these disparate cellular processes-the molecular motor KIF11. Inhibition of KIF11 with a highly specific small-molecule inhibitor stopped the growth of the more treatment-resistant glioblastoma tumor-initiating cells (TICs, or cancer stem cells) as well as non-TICs and impeded tumor initiation and self-renewal of the TIC population. Targeting KIF11 also hit the other arm of the "go or grow" cell fate decision by reducing glioma cell invasion. Administration of a KIF11 inhibitor to mice bearing orthotopic glioblastoma prolonged their survival. In its role as a shared molecular regulator of cell growth and motility across intratumoral heterogeneity, KIF11 is a compelling therapeutic target for glioblastoma. PMID- 26355034 TI - Low Self-Control and Crime in Late Adulthood. AB - This study investigates whether low self-control theory explains self-reported criminal activity in late adulthood. Cross-sectional survey data from telephone interviews conducted with individuals aged 60 years and older in Arizona and Florida (N = 2,000) are used. Regression analyses show that low self-control is related to criminal offending. The relationship between low self-control and offending persists after the introduction of potential mediators (e.g., unstructured socializing, negative emotions, and familial ties) and is even observed across different stages of late adulthood (i.e., young-old, old-old, and oldest-old) characterized by declining physical and cognitive abilities. Robustness checks using alternative measurement and modeling strategies also provide empirical support. Although strong causal inferences are limited by the nature of the data, the findings generally support the notion that low self control theory partially explains criminal offending in late adulthood. PMID- 26355033 TI - Excessive caloric intake acutely causes oxidative stress, GLUT4 carbonylation, and insulin resistance in healthy men. AB - Obesity-linked insulin resistance greatly increases the risk for type 2 diabetes, hypertension, dyslipidemia, and non-alcoholic fatty liver disease, together known as the metabolic or insulin resistance syndrome. How obesity promotes insulin resistance remains incompletely understood. Plasma concentrations of free fatty acids and proinflammatory cytokines, endoplasmic reticulum ( ER) stress, and oxidative stress are all elevated in obesity and have been shown to induce insulin resistance. However, they may be late events that only develop after chronic excessive nutrient intake. The nature of the initial event that produces insulin resistance at the beginning of excess caloric intake and weight gain remains unknown. We show that feeding healthy men with ~6000 kcal/day of the common U.S. diet [~50% carbohydrate (CHO), ~ 35% fat, and ~15% protein] for 1 week produced a rapid weight gain of 3.5 kg and the rapid onset (after 2 to 3 days) of systemic and adipose tissue insulin resistance and oxidative stress but no inflammatory or ER stress. In adipose tissue, the oxidative stress resulted in extensive oxidation and carbonylation of numerous proteins, including carbonylation of GLUT4 near the glucose transport channel, which likely resulted in loss of GLUT4 activity. These results suggest that the initial event caused by overnutrition may be oxidative stress, which produces insulin resistance, at least in part, via carbonylation and oxidation-induced inactivation of GLUT4. PMID- 26355035 TI - Deletion of integrin alpha7 subunit does not aggravate the phenotype of laminin alpha2 chain-deficient mice. AB - Laminin-211 is a major constituent of the skeletal muscle basement membrane, exerting its biological functions by binding to cell surface receptors integrin alpha7beta1 and dystroglycan (the latter is part of the dystrophin-glycoprotein complex). The importance of these molecules for normal muscle function is underscored by the fact that their respective deficiency leads to different forms of muscular dystrophy with different severity in humans and animal models. We recently demonstrated that laminin alpha2 chain and members of the dystrophin glycoprotein complex have overlapping but non-redundant roles despite being part of the same adhesion complex. To analyse whether laminin-211 and integrin alpha7 subunit have non-redundant functions we generated mice deficient in laminin alpha2 chain and integrin alpha7 subunit (dy(3K)/itga7). We show that lack of both molecules did not exacerbate the severe phenotype of laminin alpha2-chain deficient animals. They displayed the same weight, survival and dystrophic pattern of muscle biopsy, with similar degree of inflammation and fibrosis. These data suggest that laminin-211 and integrin alpha7beta1 have intersecting roles in skeletal muscle. PMID- 26355037 TI - Importance of liquid fragility for energy applications of ionic liquids. AB - Ionic liquids (ILs) are salts that are liquid close to room temperature. Their possible applications are numerous, e.g., as solvents for green chemistry, in various electrochemical devices, and even for such "exotic" purposes as spinning liquid mirrors for lunar telescopes. Here we concentrate on their use for new advancements in energy-storage and -conversion devices: Batteries, supercapacitors or fuel cells using ILs as electrolytes could be important building blocks for the sustainable energy supply of tomorrow. Interestingly, ILs show glassy freezing and the universal, but until now only poorly understood dynamic properties of glassy matter, dominate many of their physical properties. We show that the conductivity of ILs, an essential figure of merit for any electrochemical application, depends in a systematic way not only on their glass temperature but also on the so-called fragility, characterizing the non-canonical super-Arrhenius temperature dependence of their ionic mobility. PMID- 26355036 TI - Hexavalent chromium induces apoptosis in male somatic and spermatogonial stem cells via redox imbalance. AB - Hexavalent chromium [Cr(VI)], an environmental toxicant, causes severe male reproductive abnormalities. However, the actual mechanisms of toxicity are not clearly understood and have not been studied in detail. The present in vitro study aimed to investigate the mechanism of reproductive toxicity of Cr(VI) in male somatic cells (mouse TM3 Leydig cells and TM4 Sertoli cells) and spermatogonial stem cells (SSCs) because damage to or dysfunction of these cells can directly affect spermatogenesis, resulting in male infertility. Cr(VI) by inducing oxidative stress was cytotoxic to both male somatic cells and SSCs in a dose-dependent manner, and induced mitochondria-dependent apoptosis. Although the mechanism of Cr(VI)-induced cytotoxicity was similar in both somatic cells, the differences in sensitivity of TM3 and TM4 cells to Cr(VI) could be attributed, at least in part, to cell-specific regulation of P-AKT1, P-ERK1/2, and P-P53 proteins. Cr(VI) affected the differentiation and self-renewal mechanisms of SSCs, disrupted steroidogenesis in TM3 cells, while in TM4 cells, the expression of tight junction signaling and cell receptor molecules was affected as well as the secretory functions were impaired. In conclusion, our results show that Cr(VI) is cytotoxic and impairs the physiological functions of male somatic cells and SSCs. PMID- 26355038 TI - The association between visiting a primary care provider and uptake of periodic mammograms as women get older. AB - OBJECTIVE: To determine whether visits to a primary care provider (PCP) are associated with the uptake of periodic mammograms as women get older. METHODS: The cohort consisted of 2,389,889 women resident in Ontario, Canada, aged 50 to 79 at any point from 2001 to 2010, who were cancer-free and eligible for the Ontario Health Insurance Plan prior to study entry. Non-parametric estimation was used to describe the mean cumulative number of periodic mammograms for women with and without recent exposure to a PCP, as a function of age. Using age as the time scale, a recurrent event regression model was also implemented to examine the association between exposure to a PCP and rate of periodic mammograms, adjusted for income quintile and comorbidity. RESULTS: The mean observation window was 7.0 years. Uptake of periodic mammograms was significantly higher for women with recent exposure to a PCP compared with those without. This trend remained consistent as women aged, and the magnitude of the association increased for women aged 65 or older. The relative rate of periodic mammograms was lower than 1 and consistently decreased as women from lower income quintiles were compared with women from the wealthiest quintile. CONCLUSION: Visits to a PCP play an important role in uptake of periodic mammograms, and this association increases as women age. PMID- 26355039 TI - Structural Heterogeneity of Mitochondria Induced by the Microtubule Cytoskeleton. AB - By events of fusion and fission mitochondria generate a partially interconnected, irregular network of poorly specified architecture. Here, its organization is examined theoretically by taking into account the physical association of mitochondria with microtubules. Parameters of the cytoskeleton mesh are derived from the mechanics of single fibers. The model of the mitochondrial reticulum is formulated in terms of a dynamic spatial graph. The graph dynamics is modulated by the density of microtubules and their crossings. The model reproduces the full spectrum of experimentally found mitochondrial configurations. In centrosome organized cells, the chondriome is predicted to develop strong structural inhomogeneity between the cell center and the periphery. An integrated analysis of the cytoskeletal and the mitochondrial components reveals that the structure of the reticulum depends on the balance between anterograde and retrograde motility of mitochondria on microtubules, in addition to fission and fusion. We propose that it is the combination of the two processes that defines synergistically the mitochondrial structure, providing the cell with ample capabilities for its regulative adaptation. PMID- 26355040 TI - Assessing Resting Metabolic Rate in Overweight and Obese Adolescents With a Portable Indirect Calorimeter: A Pilot Study for Validation and Reliability. AB - BACKGROUND: Indirect calorimetry measured via the traditional indirect calorimeter is considered the "gold standard" for determining resting metabolic rate (RMR). Portable devices for assessing RMR are a less expensive option for measuring RMR in the clinical setting. This pilot study tested the reliability and validity of a portable device for measuring RMR, specifically in overweight and obese adolescents. MATERIALS AND METHODS: Participants aged 17-19 years (n = 19) and >=85th percentile on the Centers for Disease Control and Prevention body mass index growth curves for age and sex were recruited from a university campus. Participants completed testing on a traditional indirect calorimeter and a portable indirect calorimeter in a randomized order on 2 separate testing days. RESULTS: A paired samples t test comparing the means of the portable device and the traditional indirect calorimeter found no significant difference (P = .22). The test-retest intraclass correlation coefficient for assessing RMR was 0.91, indicating reliability of the portable indirect calorimeter. Compared with measured RMR, the Mifflin-St Jeor equation demonstrated 37% accuracy, and the Molnar equation demonstrated 57% accuracy. CONCLUSION: This pilot study found portable indirect calorimetry to be reliable and valid for assessing RMR in an overweight and obese adolescent population. In addition, this study indicates that portable indirect calorimetry may be an acceptable option for assessing RMR in this population compared with the traditional indirect calorimeter or predictive equations. PMID- 26355041 TI - The severity of initial acute kidney injury at admission of geriatric patients significantly correlates with subsequent in-hospital complications. AB - Acute kidney injury (AKI) is associated with higher hospital mortality. However, the relationship between geriatric AKI and in-hospital complications is unclear. We prospectively enrolled elderly patients (>=65 years) from general medical wards of National Taiwan University Hospital, part of whom presented AKI at admission. We recorded subsequent in-hospital complications, including catastrophic events, incident gastrointestinal bleeding, hospital-associated infections, and new-onset electrolyte imbalances. Regression analyses were utilized to assess the associations between in-hospital complications and the initial AKI severity. A total of 163 elderly were recruited, with 39% presenting AKI (stage 1: 52%, stage 2: 23%, stage 3: 25%). The incidence of any in-hospital complication was significantly higher in the AKI group than in the non-AKI group (91% vs. 68%, p < 0.01). Multiple regression analyses indicated that elderly patients presenting with AKI had significantly higher risk of developing any complication (Odds ratio [OR] = 3.51, p = 0.01) and new-onset electrolyte imbalance (OR = 7.1, p < 0.01), and a trend toward more hospital-associated infections (OR = 1.99, p = 0.08). The risk of developing complications increased with higher AKI stage. In summary, our results indicate that initial AKI at admission in geriatric patients significantly increased the risk of in-hospital complications. PMID- 26355043 TI - The Growing Burden Of Noncommunicable Diseases. PMID- 26355042 TI - Facile Discovery of a Diverse Panel of Anti-Ebola Virus Antibodies by Immune Repertoire Mining. AB - The ongoing evolution of Ebolaviruses poses significant challenges to the development of immunodiagnostics for detecting emergent viral variants. There is a critical need for the discovery of monoclonal antibodies with distinct affinities and specificities for different Ebolaviruses. We developed an efficient technology for the rapid discovery of a plethora of antigen-specific monoclonal antibodies from immunized animals by mining the VH:VL paired antibody repertoire encoded by highly expanded B cells in the draining popliteal lymph node (PLN). This approach requires neither screening nor selection for antigen binding. Specifically we show that mouse immunization with Ebola VLPs gives rise to a highly polarized antibody repertoire in CD138(+) antibody-secreting cells within the PLN. All highly expanded antibody clones (7/7 distinct clones/animal) were expressed recombinantly, and shown to recognize the VLPs used for immunization. Using this approach we obtained diverse panels of antibodies including: (i) antibodies with high affinity towards GP; (ii) antibodies which bound Ebola VLP Kissidougou-C15, the strain circulating in the recent West African outbreak; (iii) non-GP binding antibodies that recognize wild type Sudan or Bundibugyo viruses that have 39% and 37% sequence divergence from Ebola virus, respectively and (iv) antibodies to the Reston virus GP for which no antibodies have been reported. PMID- 26355044 TI - Renewed Prescriptions For An Old Remedy: Physical Activity. PMID- 26355045 TI - Noncommunicable Diseases: Three Decades Of Global Data Show A Mixture Of Increases And Decreases In Mortality Rates. AB - Noncommunicable diseases are the leading health concerns of the modern era, accounting for two-thirds of global deaths, half of all disability, and rapidly growing costs. To provide a contemporary overview of the burdens caused by noncommunicable diseases, we compiled mortality data reported by authorities in forty-nine countries for atherosclerotic cardiovascular diseases; diabetes; chronic respiratory diseases; and lung, colon, breast, cervical, liver, and stomach cancers. From 1980 to 2012, on average across all countries, mortality for cardiovascular disease, stomach cancer, and cervical cancer declined, while mortality for diabetes, liver cancer, and female chronic respiratory disease and lung cancer increased. In contrast to the relatively steep cardiovascular and cancer mortality declines observed in high-income countries, mortality for cardiovascular disease and chronic respiratory disease was flat in most low- and middle-income countries, which also experienced increasing breast and colon cancer mortality. These divergent mortality patterns likely reflect differences in timing and magnitude of risk exposures, health care, and policies to counteract the diseases. Improving both the coverage and the accuracy of mortality documentation in populous low- and middle-income countries is a priority, as is the need to rigorously evaluate societal-level interventions. Furthermore, given the complex, chronic, and progressive nature of noncommunicable diseases, policies and programs to prevent and control them need to be multifaceted and long-term, as returns on investment accrue with time. PMID- 26355046 TI - An Integrated Framework For The Prevention And Treatment Of Obesity And Its Related Chronic Diseases. AB - Improved patient experience, population health, and reduced cost of care for patients with obesity and other chronic diseases will not be achieved by clinical interventions alone. We offer here a new iteration of the Chronic Care Model that integrates clinical and community systems to address chronic diseases. Obesity contributes substantially to cardiovascular disease, type 2 diabetes mellitus, and cancer. Dietary and physical activity interventions will prevent, mitigate, and treat obesity and its related diseases. Challenges with the implementation of this model include provider training, the need to provide incentives for health systems to move beyond clinical care to link with community systems, and addressing the multiple elements necessary for integration within clinical care and with social systems. The Affordable Care Act, with its emphasis on prevention and new systems for care delivery, provides support for innovative strategies such as those proposed here. PMID- 26355047 TI - Understanding The Relationships Between Noncommunicable Diseases, Unhealthy Lifestyles, And Country Wealth. AB - The amount of international aid given to address noncommunicable diseases is minimal. Most of it is directed to wealthier countries and focuses on the prevention of unhealthy lifestyles. Explanations for the current direction of noncommunicable disease aid include that these are diseases of affluence that benefit from substantial research and development into their treatment in high income countries and are better addressed through domestic tax and policy measures to reduce risk-factor prevalence than through aid programs. This study assessed these justifications. First, we examined the relationships among premature adult mortality, defined as the probability that a person who has lived to the age of fifteen will die before the age of sixty from noncommunicable diseases; the major risk factors for these diseases; and country wealth. Second, we compared noncommunicable and communicable diseases prevalent in poor and wealthy countries alike, and their respective links to economic development. Last, we examined the respective roles that wealth and risk prevention have played in countries that achieved substantial reductions in premature mortality from noncommunicable diseases. Our results support greater investment in cost effective noncommunicable disease preventive care and treatment in poorer countries and a higher priority for reducing key risk factors, particularly tobacco use. PMID- 26355048 TI - Neighborhood Factors During Adolescence: Modest Effects On Cardiovascular Risk, Small Impact On Obesity And Depression. AB - Researchers increasingly recognize the importance of neighborhoods as a potential cause of noncommunicable disease, although the long-term impacts of early neighborhood exposures are not well understood. We used data from the prospective, nationally representative National Longitudinal Study of Adolescent to Adult Health to calculate correlations in health outcomes during adulthood among individuals who attended the same school in adolescence. These upper-bound estimates suggest that the amount of variation attributable to early neighborhoods is small in the case of adult obesity and depressive symptoms and small or modest in the case of cardiovascular risk in early adulthood. Taken together, our results suggest that the benefits of neighborhood-based interventions during adolescence in alleviating the burden of these noncommunicable diseases are likely to be relatively small. Our methods also provide a useful framework for future work that seeks to produce similar estimates on other adult conditions and for future policy discussions that attempt to compare the likely impacts of early neighborhood-level interventions across various adult outcomes. PMID- 26355049 TI - Framing Progress In Global Tobacco Control To Inform Action On Noncommunicable Diseases. AB - Much has been learned about the tobacco epidemic, including its consequences, effective measures to control it, and the actors involved. This article identifies lessons learned that are applicable to the other principal external causes of noncommunicable diseases: alcohol abuse, poor nutrition, and physical inactivity. Among these lessons are the development of evidence-based strategies such as proven cessation methods, tax increases, and smoke-free policies; the role of multinational corporations in maintaining markets and undermining control measures; and the need for strategies that reach across the life course and that begin with individuals and extend to higher levels of societal organization. Differences are also clear. Tobacco products are relatively homogeneous and have no direct benefit to consumers, whereas food and alcohol consumed in moderation are not inherently dangerous. Some tobacco-related diseases have the singular predominant cause of smoking, while many noncommunicable diseases have multiple interlocking causes such as poor diet, excess alcohol consumption, insufficient physical activity, and smoking, along with genetics. Thus, the tobacco control model of comprehensive multilevel strategies is applicable to the control of noncommunicable diseases, but the focus must be on multiple risk factors. PMID- 26355050 TI - Innovations In Diabetes Care Around the World: Case Studies Of Care Transformation Through Accountable Care Reforms. AB - The rising prevalence, health burden, and cost of chronic diseases such as diabetes have accelerated global interest in innovative care models that use approaches such as community-based care and information technology to improve or transform disease prevention, diagnosis, and treatment. Although evidence on the effectiveness of innovative care models is emerging, scaling up or extending these models beyond their original setting has been difficult. We developed a framework to highlight policy barriers-institutional, regulatory, and financial to the diffusion of transformative innovations in diabetes care. The framework builds on accountable care principles that support higher-value care, or better patient-level outcomes at lower cost. We applied this framework to three case studies from the United States, Mexico, and India to describe how innovators and policy leaders have addressed barriers, with a focus on important financing barriers to provider and consumer payment. The lessons have implications for policy reform to promote innovation through new funding approaches, institutional reforms, and performance measures with the goal of addressing the growing burdens of diabetes and other chronic diseases. PMID- 26355051 TI - Integrating Mental Health In Care For Noncommunicable Diseases: An Imperative For Person-Centered Care. AB - Mental disorders such as depression and alcohol use disorders often co-occur with other common noncommunicable diseases such as diabetes and heart disease. Furthermore, noncommunicable diseases are frequently encountered in patients with severe mental disorders such as schizophrenia. The pathways underlying the comorbidity of mental disorders and noncommunicable diseases are complex. For example, mental and physical noncommunicable diseases may have common environmental risk factors such as unhealthy lifestyles, and treatments for one condition may have side effects that increase the risk of another condition. Building on the robust evidence base for effective treatments for a range of mental disorders, there is now a growing evidence base for how such treatments can be integrated into the care of people with noncommunicable diseases. The best established delivery model is a team approach that features a nonspecialist case manager who coordinates care with primary care physicians and specialists. This approach maximizes efficiencies in person-centered care, which are essential for achieving universal health coverage for both noncommunicable diseases and mental disorders. A number of research gaps remain, but there is sufficient evidence for policy makers to immediately implement measures to integrate mental health and noncommunicable disease care in primary care platforms. PMID- 26355052 TI - Noncommunicable Diseases In East Africa: Assessing The Gaps In Care And Identifying Opportunities For Improvement. AB - The prevalence of noncommunicable diseases in East Africa is rising rapidly. Although the epidemiologic, demographic, and nutritional transitions are well under way in low-income countries, investment and attention in these countries remain focused largely on communicable diseases. We discuss existing infrastructure in communicable disease management as well as linkages between noncommunicable and communicable diseases in East Africa. We describe gaps in noncommunicable disease management within the health systems in this region. We also discuss deficiencies in addressing noncommunicable diseases from basic science research and medical training to health services delivery, public health initiatives, and access to essential medications in East Africa. Finally, we highlight the role of collaboration among East African governments and civil society in addressing noncommunicable diseases, and we advocate for a robust primary health care system that focuses on the social determinants of health. PMID- 26355053 TI - Achieving Effective Universal Health Coverage And Diagonal Approaches To Care For Chronic Illnesses. AB - Health systems in low- and middle-income countries were designed to provide episodic care for acute conditions. However, the burden of disease has shifted to be overwhelmingly dominated by chronic conditions and illnesses that require health systems to function in an integrated manner across a spectrum of disease stages from prevention to palliation. Low- and middle-income countries are also aiming to ensure health care access for all through universal health coverage. This article proposes a framework of effective universal health coverage intended to meet the challenge of chronic illnesses. It outlines strategies to strengthen health systems through a "diagonal approach." We argue that the core challenge to health systems is chronicity of illness that requires ongoing and long-term health care. The example of breast cancer within the broader context of health system reform in Mexico is presented to illustrate effective universal health coverage along the chronic disease continuum and across health systems functions. The article concludes with recommendations to strengthen health systems in order to achieve effective universal health coverage. PMID- 26355054 TI - Key Features Of Peer Support In Chronic Disease Prevention And Management. AB - Peer support from community health workers, promotores de salud, and others through community and health care organizations can provide social support and other assistance that enhances health. There is substantial evidence for both the effectiveness and the cost-effectiveness of peer support, as well as for its feasibility, reach, and sustainability. We discuss findings from Peers for Progress, a program of the American Academy of Family Physicians Foundation, to examine when peer support does not work, guide dissemination of peer support programs, and help integrate approaches such as e-health into peer support. Success factors for peer support programs include proactive implementation, attention to participants' emotions, and ongoing supervision. Reaching those whom conventional clinical and preventive services too often fail to reach; reaching whole populations, such as people with diabetes, rather than selected samples; and addressing behavioral health are strengths of peer support that can help achieve health care that is efficient and of high quality. Challenges for policy makers going forward include encouraging workforce development, balancing quality control with maintaining key features of peer support, and ensuring that underresourced organizations can develop and manage peer support programs. PMID- 26355055 TI - Living In A Country With A Strong Primary Care System Is Beneficial To People With Chronic Conditions. AB - In light of the growing pressure that multiple chronic diseases place on health care systems, we investigated whether strong primary care was associated with improved health outcomes for the chronically ill. We did this by combining country- and individual-level data for the twenty-seven countries of the European Union, focusing on people's self-rated health status and whether or not they had severe limitations or untreated conditions. We found that people with chronic conditions were more likely to be in good or very good health in countries that had a stronger primary care structure and better coordination of care. People with more than two chronic conditions benefited most: Their self-rated health was higher if they lived in countries with a stronger primary care structure, better continuity of care, and a more comprehensive package of primary care services. In general, while having access to a strong primary care system mattered for people with chronic conditions, the degree to which it mattered differed across specific subgroups (for example, people with primary care-sensitive conditions) and primary care dimensions. Primary care reforms, therefore, should be person centered, addressing the needs of subgroups of patients while also finding a balance between structure and service delivery. PMID- 26355056 TI - Cardiovascular Disease Screening By Community Health Workers Can Be Cost Effective In Low-Resource Countries. AB - In low-resource settings, a physician is not always available. We recently demonstrated that community health workers-instead of physicians or nurses-can efficiently screen adults for cardiovascular disease in South Africa, Mexico, and Guatemala. In this analysis we sought to determine the health and economic impacts of shifting this screening to community health workers equipped with either a paper-based or a mobile phone-based screening tool. We found that screening by community health workers was very cost-effective or even cost-saving in all three countries, compared to the usual clinic-based screening. The mobile application emerged as the most cost-effective strategy because it could save more lives than the paper tool at minimal extra cost. Our modeling indicated that screening by community health workers, combined with improved treatment rates, would increase the number of deaths averted from 15,000 to 110,000, compared to standard care. Policy makers should promote greater acceptance of community health workers by both national populations and health professionals and should increase their commitment to treating cardiovascular disease and making medications available. PMID- 26355057 TI - A Review Of Innovative International Financing Mechanisms To Address Noncommunicable Diseases. AB - Noncommunicable diseases have become prevalent in low- and middle-income countries. A key question that remains unresolved is how to support the development of systems to prevent and treat noncommunicable disease through international financing mechanisms. We conducted a review of articles and grey literature published from 2000 through 2014 on innovative financing models proposed or used for other disease control efforts. We found that the greatest available evidence supported pooled funding models, where funding from multiple groups is combined for a specific investment, with such models previously deployed in vaccine and infectious disease funding areas. Robust evidence also supported the viability of international transactions taxes or levies placed on specific transactions to fund investments in drug procurement and supply, and of the front-loading of development aid through bond sales, particularly to stabilize funding and subsidize drug procurement. Far less compelling evidence was available to support diaspora bonds or debt reduction programs as mechanisms to aid low- and middle-income countries' health systems in financing noncommunicable disease prevention and care services. PMID- 26355058 TI - Estimating The Potential Impact Of Insurance Expansion On Undiagnosed And Uncontrolled Chronic Conditions. AB - Policy makers have paid considerable attention to the financial implications of insurance expansion under the Affordable Care Act (ACA), but there is little evidence of the law's potential health effects. To gain insight into these effects, we analyzed data for 1999-2012 from the National Health and Nutrition Examination Survey to evaluate relationships between health insurance and the diagnosis and management of diabetes, hypercholesterolemia, and hypertension. People with insurance had significantly higher probabilities of diagnosis than matched uninsured people, by 14 percentage points for diabetes and hypercholesterolemia and 9 percentage points for hypertension. Among those with existing diagnoses, insurance was associated with significantly lower hemoglobin A1c (-0.58 percent), total cholesterol (-8.0 mg/dL), and systolic blood pressure (-2.9 mmHg). If the number of nonelderly Americans without health insurance were reduced by half, we estimate that there would be 1.5 million more people with a diagnosis of one or more of these chronic conditions and 659,000 fewer people with uncontrolled cases. Our findings suggest that the ACA could have significant effects on chronic disease identification and management, but policy makers need to consider the possible implications of those effects for the demand for health care services and spending for chronic disease. PMID- 26355059 TI - Five Policy Levers To Meet The Value Challenge In Cancer Care. AB - The burden of cancer on public finances is a serious concern for policy makers. More people are developing cancer, and as standards of care have risen, more are surviving and requiring longer-term care. Precision medicine promises better outcomes but demands commensurately higher payments for care. As both incidence and per case costs rise, we suggest that the task of expanding access to high quality cancer care poses a "value challenge" that policies in many countries are inadequate to meet. Policy makers should respond with a new approach. We explore questions that policy makers will need to consider regarding objectives, barriers, and levers for policy development. We use transparency and accountability as cornerstones of a new approach to promote value-based decision making. Although barriers to advancing this agenda are formidable, we recommend that governments define common standards for value-based accounting; serve as information brokers for evidence development; pioneer value-based procurement of goods and services; engage in deliberative democracy in cancer care; and educate communities to facilitate knowledge sharing between communities of patients, their caretakers, and researchers. PMID- 26355060 TI - Overcoming Obstacles To Enable Access To Medicines For Noncommunicable Diseases In Poor Countries. AB - The modern access-to-medicines movement grew largely out of the civil-society reaction to the HIV/AIDS pandemic three decades ago. While the movement was successful with regard to HIV/AIDS medications, the increasingly urgent challenge to address access to medicines for noncommunicable diseases has lagged behind and, in some cases, has been forgotten. In this article we first ask what causes the access gap with respect to lifesaving essential noncommunicable disease medicines and then what can be done to close the gap. Using the example of the push for access to antiretrovirals for HIV/AIDS patients for comparison, we highlight the problems of inadequate global financing and procurement for noncommunicable disease medications, intellectual property barriers and concerns raised by the pharmaceutical industry, and challenges to building stronger civil society organizations and a patient and humanitarian response from the bottom up to demand treatment. We provide targeted policy recommendations, specific to the public sector, the private sector, and civil society, with the goal of improving access to noncommunicable disease medications globally. PMID- 26355061 TI - Increasing Prescription Length Could Cut Cardiovascular Disease Burden And Produce Savings In South Africa. AB - South Africa's rates of statin use are among the world's lowest, despite statins' demonstrated effectiveness for people with a high blood cholesterol level or history of cardiovascular disease. Almost 5 percent of the country's total mortality has been attributed to high cholesterol levels, fueled in part by low levels of statin adherence. Drawing upon experience elsewhere, we used a microsimulation model of cardiovascular disease to investigate the health and economic impacts of increasing prescription length from the standard thirty days to either sixty or ninety days, for South African adults on a stable statin regimen. Increasing prescription length to sixty or ninety days could save 1,694 or 2,553 lives per million adults, respectively. In addition, annual per patient costs related to cardiovascular disease would decrease by $152.41 and $210.29, respectively. Savings would largely accrue to patients in the form of time savings and reduced transportation costs, as a result of less frequent trips to the pharmacy. Increasing statin prescription length would both save resources and improve health outcomes in South Africa. PMID- 26355062 TI - Increased Use Of Prescription Drugs Reduces Medical Costs In Medicaid Populations. AB - We used data on more than 1.5 million Medicaid enrollees to examine the impact of changes in prescription drug use on medical costs. For three distinct groups of enrollees, we estimated the effects of aggregate prescription drug use-and, more specifically, the use of medications to treat eight chronic noncommunicable diseases-on total nondrug, inpatient, outpatient, and other Medicaid spending. We found that a 1 percent increase in overall prescription drug use was associated with decreases in total nondrug Medicaid costs by 0.108 percent for blind or disabled adults, 0.167 percent for other adults, and 0.041 percent for children. Reductions in combined inpatient and outpatient spending from increased drug utilization in Medicaid were similar to an estimate for Medicare by the Congressional Budget Office. Moving forward, policy makers evaluating proposed changes that alter medication use among the nearly seventy million Medicaid recipients should consider the net effects on program spending to ensure that scarce federal and state health care dollars are allocated efficiently. PMID- 26355063 TI - Health Savings Accounts: Growth Concentrated Among High-Income Households And Large Employers. PMID- 26355064 TI - Medical Myths: Unprepared For The End Stages Of End-Stage Kidney Disease. PMID- 26355065 TI - Recent Foundation Grants: Cancer And Diabetes. PMID- 26355067 TI - The Impact Of Smoking On Cancer Mortality. PMID- 26355068 TI - Smoking And Cancer Mortality: The Authors Reply. PMID- 26355069 TI - Massachusetts Graduated Driver-Licensing Program. PMID- 26355070 TI - Graduated Driver-Licensing: The Authors Reply. PMID- 26355071 TI - The Nonprofit Hospital Tax Exemption. PMID- 26355072 TI - Tax-Exempt Hospitals: The Authors Reply. PMID- 26355073 TI - Errata. PMID- 26355075 TI - HOPE Centre Meets Needs Of South African Community. PMID- 26355077 TI - Polymorphic transitions of diborane at sub- and near-megabar pressures. AB - Recent theoretical investigations of high-pressure structures of diborane have yielded many intriguing predictions which have so far remained untested due to challenges of acquiring experimental data at extreme pressures. Here we report new pressure-induced polymorphic transformations of crystalline diborane observed between 36 and 88 GPa by in situ Raman spectroscopy and interpreted using electronic structure calculations. Two previously unknown phase transitions are identified near 42 and 57 GPa, as evidenced by significant changes in the Raman profiles. The corresponding new phases, labeled IV and V, consist of B2H6 molecules and have triclinic unit cells (P), as deduced through evolutionary structure search and comparison of experimental and simulated Raman spectra. Density-functional calculations suggest that, at pressures above 110 GPa, phase V will form new molecular structures consisting of one-dimensional (BH3)n chains and will become metallic near 138 GPa. Our findings make a significant contribution to the elucidation of the structures and properties of diborane in the near-megabar pressure region. PMID- 26355078 TI - The genetic architecture of non-syndromic thoracic aortic aneurysm. PMID- 26355076 TI - Collagen Q and anti-MuSK autoantibody competitively suppress agrin/LRP4/MuSK signaling. AB - MuSK antibody-positive myasthenia gravis (MuSK-MG) accounts for 5 to 15% of autoimmune MG. MuSK and LRP4 are coreceptors for agrin in the signaling pathway that causes clustering of acetylcholine receptor (AChR). MuSK also anchors the acetylcholinesterase (AChE)/collagen Q (ColQ) complex to the synaptic basal lamina. We previously reported that anti-MuSK antibodies (MuSK-IgG) block binding of ColQ to MuSK and cause partial endplate AChE deficiency in mice. We here analyzed the physiological significance of binding of ColQ to MuSK and block of this binding by MuSK-IgG. In vitro plate-binding assay showed that MuSK-IgG blocked MuSK-LRP4 interaction in the presence of agrin. Passive transfer of MuSK IgG to Colq-knockout mice attenuated AChR clustering, indicating that lack of ColQ is not the key event causing defective clustering of AChR in MuSK-MG. In three MuSK-MG patients, the MuSK antibodies recognized the first and fourth immunoglobulin-like domains (Ig1 and Ig4) of MuSK. In two other MuSK-MG patients, they recognized only the Ig4 domain. LRP4 and ColQ also bound to the Ig1 and Ig4 domains of MuSK. Unexpectedly, the AChE/ColQ complex blocked MuSK-LRP4 interaction and suppressed agrin/LRP4/MuSK signaling. Quantitative analysis showed that MuSK-IgG suppressed agrin/LRP4/MuSK signaling to a greater extent than ColQ. PMID- 26355079 TI - Cochrane corner: prehospital versus in-hospital thrombolysis for ST-elevation myocardial infarction. PMID- 26355080 TI - Action mechanism of corticosteroids to aggravate Guillain-Barre syndrome. AB - Corticosteroids have been proved to be ineffective for Guillain-Barre syndrome, but the mechanism remains unknown. In a rabbit model of axonal Guillain-Barre syndrome, treatment with corticosteroids significantly reduced macrophage infiltration in the spinal ventral roots and the survival rate as well as clinical improvement. On 30(th) day after onset, there was significantly higher frequency of axonal degeneration in the corticosteroids-treated rabbits than saline-treated rabbits. Corticosteroids may reduce the scavengers that play a crucial role for nerve regeneration, thus delay the recovery of this disease. PMID- 26355081 TI - Consequences of HLA-B*13-Associated Escape Mutations on HIV-1 Replication and Nef Function. AB - HLA-B*13 is associated with superior in vivo HIV-1 viremia control. Protection is thought to be mediated by sustained targeting of key cytotoxic T lymphocyte (CTL) epitopes and viral fitness costs of CTL escape in Gag although additional factors may contribute. We assessed the impact of 10 published B*13-associated polymorphisms in Gag, Pol, and Nef, in 23 biologically relevant combinations, on HIV-1 replication capacity and Nef-mediated reduction of cell surface CD4 and HLA class I expression. Mutations were engineered into HIV-1NL4.3, and replication capacity was measured using a green fluorescent protein (GFP) reporter T cell line. Nef-mediated CD4 and HLA-A*02 downregulation was assessed by flow cytometry, and T cell recognition of infected target cells was measured via coculture with an HIV-specific luciferase reporter cell line. When tested individually, only Gag-I147L and Gag-I437L incurred replicative costs (5% and 17%, respectively), consistent with prior reports. The Gag-I437L-mediated replication defect was rescued to wild-type levels by the adjacent K436R mutation. A novel B*13 epitope, comprising 8 residues and terminating at Gag147, was identified in p24(Gag) (GQMVHQAIGag140-147). No other single or combination Gag, Pol, or Nef mutant impaired viral replication. Single Nef mutations did not affect CD4 or HLA downregulation; however, the Nef double mutant E24Q-Q107R showed 40% impairment in HLA downregulation with no evidence of Nef stability defects. Moreover, target cells infected with HIV-1-NefE24Q-Q107R were recognized better by HIV-specific T cells than those infected with HIV-1NL4.3 or single Nef mutants. Our results indicate that CTL escape in Gag and Nef can be functionally costly and suggest that these effects may contribute to long-term HIV-1 control by HLA-B*13. IMPORTANCE: Protective effects of HLA-B*13 on HIV-1 disease progression are mediated in part by fitness costs of CTL escape mutations in conserved Gag epitopes, but other mechanisms remain incompletely known. We extend our knowledge of the impact of B*13-driven escape on HIV-1 replication by identifying Gag-K436R as a compensatory mutation for the fitness-costly Gag I437L. We also identify Gag-I147L, the most rapidly and commonly selected B*13 driven substitution in HIV-1, as a putative C-terminal anchor residue mutation in a novel B*13 epitope. Most notably, we identify a novel escape-driven fitness defect: B*13-driven substitutions E24Q and Q107R in Nef, when present together, substantially impair this protein's ability to downregulate HLA class I. This, in turn, increases the visibility of infected cells to HIV-specific T cells. Our results suggest that B*13-associated escape mutations impair HIV-1 replication by two distinct mechanisms, that is, by reducing Gag fitness and dampening Nef immune evasion function. PMID- 26355082 TI - Promotion of Cancer Stem-Like Cell Properties in Hepatitis C Virus-Infected Hepatocytes. AB - We have previously reported that hepatitis C virus (HCV) infection of primary human hepatocytes (PHH) induces the epithelial mesenchymal transition (EMT) state and extends hepatocyte life span (S. K. Bose, K. Meyer, A. M. Di Bisceglie, R. B. Ray, and R. Ray, J Virol 86:13621-13628, 2012, http://dx.doi.org/10.1128/JVI.02016-12). These hepatocytes displayed sphere formation on ultralow binding plates and survived for more than 12 weeks. The sphere-forming hepatocytes expressed a number of cancer stem-like cell (CSC) markers, including high levels of the stem cell factor receptor c-Kit. The c-Kit receptor is regarded as one of the CSC markers in hepatocellular carcinoma (HCC). Analysis of c-Kit mRNA displayed a significant increase in the liver biopsy specimens of chronically HCV-infected patients. We also found c-Kit is highly expressed in transformed human hepatocytes (THH) infected in vitro with cell culture-grown HCV genotype 2a. Further studies suggested that HCV core protein significantly upregulates c-Kit expression at the transcriptional level. HCV infection of THH led to a significant increase in the number of spheres displayed on ultralow binding plates and in enhanced EMT and CSC markers and tumor growth in immunodeficient mice. The use of imatinib or dasatinib as a c-Kit inhibitor reduced the level of sphere-forming cells in culture. The sphere-forming cells were sensitive to treatment with sorafenib, a multikinase inhibitor, that is used for HCC treatment. Further, stattic, an inhibitor of the Stat3 molecule, induced sphere-forming cell death. A combination of sorafenib and stattic had a significantly stronger effect, leading to cell death. These results suggested that HCV infection potentiates CSC generation, and selected drugs can be targeted to efficiently inhibit cell growth. IMPORTANCE: HCV infection may develop into HCC as an end-stage liver disease. We focused on understanding the mechanism for the risk of HCC from chronic HCV infection and identified targets for treatment. HCV-infected primary and transformed human hepatocytes (PHH or THH) generated CSC. HCV-induced spheres were highly sensitive to cell death from sorafenib and stattic treatment. Thus, our study is highly significant for HCV-associated HCC, with the potential for developing a target-specific strategy for improved therapies. PMID- 26355083 TI - Requirement for Host RNA-Silencing Components and the Virus-Silencing Suppressor when Second-Site Mutations Compensate for Structural Defects in the 3' Untranslated Region. AB - Turnip crinkle virus (TCV) contains a structured 3' region with hairpins and pseudoknots that form a complex network of noncanonical RNA:RNA interactions supporting higher-order structure critical for translation and replication. We investigated several second-site mutations in the p38 coat protein open reading frame (ORF) that arose in response to a mutation in the asymmetric loop of a critical 3' untranslated region (UTR) hairpin that disrupts local higher-order structure. All tested second-site mutations improved accumulation of TCV in conjunction with a partial reversion of the primary mutation (TCV-rev1) but had neutral or a negative effect on wild-type (wt) TCV or TCV with the primary mutation. SHAPE (selective 2'-hydroxyl acylation analyzed by primer extension) structure probing indicated that these second-site mutations reside in an RNA domain that includes most of p38 (domain 2), and evidence for RNA:RNA interactions between domain 2 and 3'UTR-containing domain 1 was found. However, second-site mutations were not compensatory in the absence of p38, which is also the TCV silencing suppressor, or in dcl-2/dcl4 or ago1/ago2 backgrounds. One second-site mutation reduced silencing suppressor activity of p38 by altering one of two GW motifs that are required for p38 binding to double-stranded RNAs (dsRNAs) and interaction with RNA-induced silencing complex (RISC)-associated AGO1/AGO2. Another second-site mutation substantially reduced accumulation of TCV rev1 in the absence of p38 or DCL2/DCL4. We suggest that the second-site mutations in the p38 ORF exert positive effects through a similar downstream mechanism, either by enhancing accumulation of beneficial DCL-produced viral small RNAs that positively regulate the accumulation of TCV-rev1 or by affecting the susceptibility of TCV-rev1 to RISC loaded with viral small RNAs. IMPORTANCE: Genomes of positive-strand RNA viruses fold into high-order RNA structures. Viruses with mutations in regions critical for translation and replication often acquire second-site mutations that exert a positive compensatory effect through reestablishment of canonical base pairing with the altered region. In this study, two distal second-site mutations that individually arose in response to a primary mutation in a critical 3' UTR hairpin in the genomic RNA of turnip crinkle virus did not directly interact with the primary mutation. Although different second site changes had different attributes, compensation was dependent on the production of the viral p38 silencing suppressor and on the presence of silencing required DCL and AGO proteins. Our results provide an unexpected connection between a 3' UTR primary-site mutation proposed to disrupt higher-order structure and the RNA-silencing machinery. PMID- 26355084 TI - Cooperation between the Hepatitis C Virus p7 and NS5B Proteins Enhances Virion Infectivity. AB - The molecular mechanisms that govern hepatitis C virus (HCV) assembly, release, and infectivity are still not yet fully understood. In the present study, we sequenced a genotype 2A strain of HCV (JFH-1) that had been cell culture adapted in Huh-7.5 cells to produce nearly 100-fold-higher viral titers than the parental strain. Sequence analysis identified nine mutations in the genome, present within both the structural and nonstructural genes. The infectious clone of this virus containing all nine culture-adapted mutations had 10-fold-higher levels of RNA replication and RNA release into the supernatant but had nearly 1,000-fold-higher viral titers, resulting in an increased specific infectivity compared to wild type JFH-1. Two mutations, identified in the p7 polypeptide and NS5B RNA dependent RNA polymerase, were sufficient to increase the specific infectivity of JFH-1. We found that the culture-adapted mutation in p7 promoted an increase in the size of cellular lipid droplets following transfection of viral RNA. In addition, we found that the culture-adaptive mutations in p7 and NS5B acted synergistically to enhance the specific viral infectivity of JFH-1 by decreasing the level of sphingomyelin in the virion. Overall, these results reveal a genetic interaction between p7 and NS5B that contributes to virion specific infectivity. Furthermore, our results demonstrate a novel role for the RNA-dependent RNA polymerase NS5B in HCV assembly. IMPORTANCE: Hepatitis C virus assembly and release depend on viral interactions with host lipid metabolic pathways. Here, we demonstrate that the viral p7 and NS5B proteins cooperate to promote virion infectivity by decreasing sphingomyelin content in the virion. Our data uncover a new role for the viral RNA-dependent RNA polymerase NS5B and p7 proteins in contributing to virion morphogenesis. Overall, these findings are significant because they reveal a genetic interaction between p7 and NS5B, as well as an interaction with sphingomyelin that regulates virion infectivity. Our data provide new strategies for targeting host lipid-virus interactions as potential targets for therapies against HCV infection. PMID- 26355085 TI - Virus Multiplicity of Infection Affects Type I Interferon Subtype Induction Profiles and Interferon-Stimulated Genes. AB - Type I interferons (IFNs) are induced upon viral infection and important mediators of innate immunity. While there is 1 beta interferon (IFN-beta) protein, there are 12 different IFN-alpha subtypes. It has been reported extensively that different viruses induce distinct patterns of IFN subtypes, but it has not been previously shown how the viral multiplicity of infection (MOI) can affect IFN induction. In this study, we discovered the novel finding that human U937 cells infected with 2 different concentrations of Sendai virus (SeV) induce 2 distinct type I IFN subtype profiles. Cells infected at the lower MOI induced more subtypes than cells infected at the higher MOI. We found that this was due to the extent of signaling through the IFN receptor (IFNAR). The cells infected at the lower viral MOI induced the IFNAR2-dependent IFN-alpha subtypes 4, 6, 7, 10, and 17, which were not induced in cells infected at higher virus concentrations. IFN-beta and IFN-alpha1, -2, and -8 were induced in an IFNAR independent manner in cells infected at both virus concentrations. IFN-alpha5, 14, -16, and -21 were induced in an IFNAR-dependent manner in cells infected at lower virus concentrations and in an IFNAR-independent manner in cells infected at higher virus concentrations. These differences in IFN subtype profiles in the 2 virus concentrations also resulted in distinct interferon-stimulated gene induction. These results present the novel finding that different viral MOIs differentially activate JAK/STAT signaling through the IFNAR, which greatly affects the profile of IFN subtypes that are induced. IMPORTANCE: Type I IFNs are pleiotropic cytokines that are instrumental in combating viral diseases. Understanding how the individual subtypes are induced is important in developing strategies to block viral replication. Many studies have reported that different viruses induce distinct type I IFN subtype profiles due to differences in the way viruses are sensed in different cell types. However, we report in our study the novel finding that the amount of virus used to infect a system can also affect which type I IFN subtypes are induced due to the extent of activation of certain signaling pathways. These distinct IFN subtype profiles in cells infected at different MOIs are correlated with differences in interferon-stimulated gene induction, indicating that the same virus can induce distinct antiviral responses depending on the MOI. Because type I IFNs are used as therapeutic agents to treat viral diseases, understanding their antiviral mechanisms can enhance clinical treatments. PMID- 26355086 TI - Y-Box Binding Protein 1 Stabilizes Hepatitis C Virus NS5A via Phosphorylation Mediated Interaction with NS5A To Regulate Viral Propagation. AB - Replication of hepatitis C virus (HCV) is dependent on virus-encoded proteins and numerous cellular factors. DDX3 is a well-known host cofactor of HCV replication. In this study, we investigated the role of a DDX3-interacting protein, Y-box binding protein 1 (YB-1), in the HCV life cycle. Both YB-1 and DDX3 interacted with the viral nonstructural protein NS5A. During HCV infection, YB-1 partially colocalized with NS5A and the HCV replication intermediate double-stranded RNA (dsRNA) in HCV-infected Huh-7.5.1 cells. Despite sharing the same interacting partners, YB-1 participated in HCV RNA replication but was dispensable in steady state HCV RNA replication, different from the action of DDX3. Moreover, knockdown of YB-1 in HCV-infected cells prevented infectious virus production and reduced the ratio of hyperphosphorylated (p58) to hypophosphorylated (p56) forms of NS5A, whereas DDX3 silencing did not affect the ratio of the p58 and p56 phosphoforms of NS5A. Interestingly, silencing of YB-1 severely reduced NS5A protein stability in NS5A-ectopically expressing, replicon-containing, and HCV-infected cells. Furthermore, mutations of serine 102 of YB-1 affected both YB-1-NS5A interaction and NS5A-stabilizing activity of YB-1, indicating that this Akt phosphorylation site of YB-1 plays an important role in stabilizing NS5A. Collectively, our results support a model in which the event of YB-1 phosphorylation-mediated interaction with NS5A results in stabilizing NS5A to sustain HCV RNA replication and infectious HCV production. Overall, our study may reveal a new aspect for the development of novel anti-HCV drugs. IMPORTANCE: Chronic hepatitis C virus (HCV) infection induces liver cirrhosis and hepatocellular carcinoma. The viral nonstructural protein NS5A co-opting various cellular signaling pathways and cofactors to support viral genome replication and virion assembly is a new strategy for anti-HCV drug development. NS5A phosphorylation is believed to modulate switches between different stages of the HCV life cycle. In this study, we identified the cellular protein YB-1 as a novel NS5A-interacting protein. YB-1 is a multifunctional protein participating in oncogenesis and is an oncomarker of hepatocellular carcinoma (HCC). We found that YB-1 protects NS5A from degradation and likely regulates NS5A phosphorylation through its phosphorylation-dependent interaction with NS5A, which might be controlled by HCV-induced signaling pathways. Our observations suggest a model in which HCV modulates NS5A level and the ratio of the p58 and p56 phosphoforms for efficient viral propagation via regulation of cellular signaling inducing YB-1 phosphorylation. Our finding may provide new aspects for developing novel anti-HCV drugs. PMID- 26355087 TI - Kaposi's Sarcoma-Associated Herpesvirus Viral Interferon Regulatory Factor 1 Interacts with a Member of the Interferon-Stimulated Gene 15 Pathway. AB - Kaposi's sarcoma-associated herpesvirus (KSHV) is a gammaherpesvirus known to establish lifelong latency in the human host. We and others have previously shown that three KSHV homologs of cellular interferon regulatory factors (IRFs), known as viral IRFs (vIRFs), participate in evasion of the host interferon (IFN) response. We report that vIRF1 interacts with the cellular interferon-stimulated gene 15 (ISG15) E3 ligase, HERC5, in the context of Toll-like receptor 3 (TLR3) activation and IFN induction. The ISG15 protein is covalently conjugated to target proteins upon activation of the interferon response. Interaction between vIRF1 and HERC5 was confirmed by immunoprecipitation, and the region between amino acids 224 and 349 of vIRF1 was required for interaction with HERC5. We further report that expression of vIRF1 in the context of TLR3 activation results in decreased ISG15 conjugation of proteins. Specifically, TLR3-induced ISG15 conjugation and protein levels of cellular IRF3, a known ISG15 target, were decreased in the presence of vIRF1 compared to the control. vIRF1 itself was also identified as a target of ISG15 conjugation. KSHV-infected cells exhibited increased ISG15 conjugation upon reactivation from latency in coordination with increased IFN. Furthermore, knockdown of ISG15 in latently infected cells resulted in a higher level of KSHV reactivation and an increase in infectious virus. These data suggest that the KSHV vIRF1 protein affects ISG15 conjugation and interferon responses and may contribute to effective KSHV replication. IMPORTANCE: The KSHV vIRF1 protein can inhibit interferon activation in response to viral infection. We identified a cellular protein named HERC5, which is the major ligase for ISG15, as a vIRF1 binding partner. vIRF1 association with HERC5 altered ISG15 modification of cellular proteins, and knockdown of ISG15 augmented reactivation of KSHV from latency. PMID- 26355088 TI - Mutational Disruption of cis-Acting Replication Element 2C in Coxsackievirus B3 Leads to 5'-Terminal Genomic Deletions. AB - Following natural human or experimental murine infections and in cell culture, coxsackievirus B (CVB) RNA can persist for weeks in the absence of a cytopathic effect, yet viral RNA remains detectable. Our earlier studies demonstrated that this persistence produced viral RNA with up to 49 nucleotide deletions at the genomic 5' terminus which partially degraded the cloverleaf (or domain I), an RNA structure required for efficient viral replication. A cis-acting replication element (CRE) in the 2C protein-coding region [CRE(2C)] templates the addition of two uridine residues to the virus genome-encoded RNA replication primer VPg prior to positive-strand synthesis. Because our previous work also demonstrated that the genomes of CVB with a 5'-terminal deletion (CVB-TD) have VPg covalently linked, even though they rarely terminate in the canonical UU donated by CRE(2C) mediated uridylylation of VPg, we hypothesized that a functional (uridylylating) CRE(2C) would be unnecessary for CVB-TD replication. Using the same 16 mutations in the CVB3 CRE(2C) structure that were considered lethal for this virus by others, we demonstrate here both in infected cell cultures and in mice that wild type (wt) and CVB3-TD strains carrying these mutations with a nonuridylylating CRE(2C) are viable. While the wt genome with the mutated CRE(2C) displays suppressed replication levels similar to those observed in a CVB3-TD strain, mutation of the CRE(2C) function in a CVB3-TD strain does not further decrease replication. Finally, we show that replication of the parental CVB3 strain containing the mutated CRE(2C) drives the de novo generation of genomic deletions at the 5' terminus. IMPORTANCE: In this report, we demonstrate that while CVB can replicate without a uridylylating CRE(2C), the replication rate suffers significantly. Further, deletions at the 5' terminus of the genome are generated in this virus population, with this virus population supplanting the wild-type population. This demonstrates that VPg can prime without being specifically uridylylated and that this priming is error prone, resulting in the loss of sequence information from the 5' terminus. These findings have significance when considering the replication of human enteroviruses, and we believe that these data are unattainable in a cell-free system due to the poor replication of these CRE-deficient viruses. PMID- 26355089 TI - Computational and Functional Analysis of the Virus-Receptor Interface Reveals Host Range Trade-Offs in New World Arenaviruses. AB - Animal viruses frequently cause zoonotic disease in humans. As these viruses are highly diverse, evaluating the threat that they pose remains a major challenge, and efficient approaches are needed to rapidly predict virus-host compatibility. Here, we develop a combined computational and experimental approach to assess the compatibility of New World arenaviruses, endemic in rodents, with the host TfR1 entry receptors of different potential new host species. Using signatures of positive selection, we identify a small motif on rodent TfR1 that conveys species specificity to the entry of viruses into cells. However, we show that mutations in this region affect the entry of each arenavirus differently. For example, a human single nucleotide polymorphism (SNP) in this region, L212V, makes human TfR1 a weaker receptor for one arenavirus, Machupo virus, but a stronger receptor for two other arenaviruses, Junin and Sabia viruses. Collectively, these findings set the stage for potential evolutionary trade-offs, where natural selection for resistance to one virus may make humans or rodents susceptible to other arenavirus species. Given the complexity of this host-virus interplay, we propose a computational method to predict these interactions, based on homology modeling and computational docking of the virus-receptor protein-protein interaction. We demonstrate the utility of this model for Machupo virus, for which a suitable cocrystal structural template exists. Our model effectively predicts whether the TfR1 receptors of different species will be functional receptors for Machupo virus entry. Approaches such at this could provide a first step toward computationally predicting the "host jumping" potential of a virus into a new host species. IMPORTANCE: We demonstrate how evolutionary trade-offs may exist in the dynamic evolutionary interplay between viruses and their hosts, where natural selection for resistance to one virus could make humans or rodents susceptible to other virus species. We present an algorithm that predicts which species have cell surface receptors that make them susceptible to Machupo virus, based on computational docking of protein structures. Few molecular models exist for predicting the risk of spillover of a particular animal virus into humans or new animal populations. Our results suggest that a combination of evolutionary analysis, structural modeling, and experimental verification may provide an efficient approach for screening and assessing the potential spillover risks of viruses circulating in animal populations. PMID- 26355090 TI - Exclusive Decoration of Simian Immunodeficiency Virus Env with High-Mannose Type N-Glycans Is Not Compatible with Mucosal Transmission in Rhesus Macaques. AB - Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) envelope (Env) proteins are extensively decorated with N-glycans, predominantly of the high-mannose type. However, it is unclear how high-mannose N-glycans on Env impact viral spread. We show that exclusive modification of SIV Env with these N-glycans reduces viral infectivity and abrogates mucosal transmission, despite increasing viral capture by immune cell lectins. Thus, high-mannose N glycans have opposed effects on SIV infectivity and lectin reactivity, and a balance might be required for efficient mucosal transmission. PMID- 26355092 TI - Regulation of PACT-Mediated Protein Kinase Activation by the OV20.0 Protein of Orf Virus. AB - Double-stranded RNA (dsRNA)-activated protein kinase (PKR), a major component of the cellular antiviral system, is activated by the binding of either dsRNA or the cellular PKR activator, the PACT protein. The suppression of PKR activation is one of the main strategies that viruses employ to circumvent interferon signaling. Orf virus (ORFV), a parapoxvirus from the Poxviridae family, causes contagious pustular dermatitis in small ruminants. Previous studies have demonstrated that various OV20.0 isoforms, encoded by the OV20.0L gene, are able to inhibit PKR activation both by sequestering dsRNA and by physically interacting with PKR in vitro. Thus, this gene acts as a virulence factor of ORFV when tested using a mouse infection model. In the present study, the regions within OV20.0 that interact with dsRNA and with PKR have been mapped. Furthermore, this study demonstrates for the first time that OV20.0 is also able to interact with the dsRNA binding domain of PACT and that the presence of dsRNA strengthened the interaction of these two molecules. The presence of OV20.0 diminishes PKR phosphorylation when this is stimulated by PACT. Nevertheless, the association of OV20.0 with PKR, rather than with PACT, was found to be essential for reducing PACT-mediated PKR phosphorylation. These observations elucidate a new strategy whereby innate immunity can be evaded by ORFV.IMPORTANCE Our previous study indicated that ORFV's two OV20.0 isoforms act as a PKR antagonist via sequestering the PKR activator, dsRNA, and by interacting with PKR, leading to an inhibition of PKR activation (Y. Y. Tseng, F. Y. Lin, S. F. Cheng, D. Tscharke, S. Chulakasian, C. C. Chou, Y. F. Liu, W. S. Chang, M. L. Wong, and W. L. Hsu, J Virol 89:4966-4979, 2015, doi:10.1128/JVI.03714-14). In the current study, the possible mechanisms by which OV20.0 protein counteracts PKR activation were studied in depth. OV20.0 is able to bind PKR and its two activators, dsRNA and PACT. In addition, OV20.0 binds directly to the RNA binding domains (RBDs) of PKR, and this interaction does not require dsRNA. Moreover, OV20.0 interacts with or occupies the RBD2 and the kinase domain of PKR, which then prevents PACT binding to PKR. Finally, OV20.0 associates with PACT via the RBDs, which may reduce the ability of PACT to induce PKR activation. The findings in this study provide new concepts in relation to how ORFV modulates PKR activation. PMID- 26355091 TI - Successive Respiratory Syncytial Virus Epidemics in Local Populations Arise from Multiple Variant Introductions, Providing Insights into Virus Persistence. AB - Respiratory syncytial virus (RSV) is a global respiratory pathogen of humans, with infection occurring characteristically as recurrent seasonal epidemics. Unlike influenza viruses, little attention has been paid to the mechanism underlying worldwide spread and persistence of RSV and how this may be discerned through an improved understanding of the introduction and persistence of RSV in local communities. We analyzed 651 attachment (G) glycoprotein nucleotide sequences of RSV B collected over 11 epidemics (2002 to 2012) in Kilifi, Kenya, and contemporaneous data collected elsewhere in Kenya and 18 other countries worldwide (2002 to 2012). Based on phylogeny, genetic distance and clustering patterns, we set out pragmatic criteria to classify local viruses into distinct genotypes and variants, identifying those newly introduced and those locally persisting. Three genotypes were identified in the Kilifi data set: BA (n = 500), SAB1 (n = 148), and SAB4 (n = 3). Recurrent RSV epidemics in the local population were composed of numerous genetic variants, most of which have been newly introduced rather than persisting in the location from season to season. Global comparison revealed that (i) most Kilifi variants do not cluster closely with strains from outside Kenya, (ii) some Kilifi variants were closely related to those observed outside Kenya (mostly Western Europe), and (iii) many variants were circulating elsewhere but were never detected in Kilifi. These results are consistent with the hypothesis that year-to-year presence of RSV at the local level (i.e., Kilifi) is achieved primarily, but not exclusively, through introductions from a pool of variants that are geographically restricted (i.e., to Kenya or to the region) rather than global. IMPORTANCE: The mechanism by which RSV persists and reinvades local populations is poorly understood. We investigated this by studying the temporal patterns of RSV variants in a rural setting in tropical Africa and comparing these variants with contemporaneous variants circulating in other countries. We found that periodic seasonal RSV transmission at the local level appears to require regular new introductions of variants. However, importantly, the evidence suggests that the source of new variants is mostly geographically restricted, and we hypothesize that year-to year RSV persistence is at the country level rather than the global level. This has implications for control. PMID- 26355093 TI - Sulfolobus Spindle-Shaped Virus 1 Contains Glycosylated Capsid Proteins, a Cellular Chromatin Protein, and Host-Derived Lipids. AB - Geothermal and hypersaline environments are rich in virus-like particles, among which spindle-shaped morphotypes dominate. Currently, viruses with spindle- or lemon-shaped virions are exclusive to Archaea and belong to two distinct viral families. The larger of the two families, the Fuselloviridae, comprises tail less, spindle-shaped viruses, which infect hosts from phylogenetically distant archaeal lineages. Sulfolobus spindle-shaped virus 1 (SSV1) is the best known member of the family and was one of the first hyperthermophilic archaeal viruses to be isolated. SSV1 is an attractive model for understanding virus-host interactions in Archaea; however, the constituents and architecture of SSV1 particles remain only partially characterized. Here, we have conducted an extensive biochemical characterization of highly purified SSV1 virions and identified four virus-encoded structural proteins, VP1 to VP4, as well as one DNA binding protein of cellular origin. The virion proteins VP1, VP3, and VP4 undergo posttranslational modification by glycosylation, seemingly at multiple sites. VP1 is also proteolytically processed. In addition to the viral DNA-binding protein VP2, we show that viral particles contain the Sulfolobus solfataricus chromatin protein Sso7d. Finally, we provide evidence indicating that SSV1 virions contain glycerol dibiphytanyl glycerol tetraether (GDGT) lipids, resolving a long standing debate on the presence of lipids within SSV1 virions. A comparison of the contents of lipids isolated from the virus and its host cell suggests that GDGTs are acquired by the virus in a selective manner from the host cytoplasmic membrane, likely during progeny egress. IMPORTANCE: Although spindle-shaped viruses represent one of the most prominent viral groups in Archaea, structural data on their virion constituents and architecture still are scarce. The comprehensive biochemical characterization of the hyperthermophilic virus SSV1 presented here brings novel and significant insights into the organization and architecture of spindle-shaped virions. The obtained data permit the comparison between spindle-shaped viruses residing in widely different ecological niches, improving our understanding of the adaptation of viruses with unusual morphotypes to extreme environmental conditions. PMID- 26355095 TI - The Nucleoprotein Is Required for Lymphocytic Choriomeningitis Virus-Based Vaccine Vector Immunogenicity. AB - Recombinant glycoprotein-deficient lymphocytic choriomeningitis virus-based vaccine vectors (rLCMV/DeltaGP) are potent CD8(+) T cell inducers. To investigate the underlying molecular requirements, we generated a nucleoprotein-deficient vector counterpart (rLCMV/DeltaNP). NP but not GP is a minimal trans-acting factor for viral transcription and genome replication. We found that, unlike rLCMV/DeltaGP, rLCMV/DeltaNP failed to elicit detectable CD8(+) T cell responses unless NP was trans complemented in a transgenic host. Hence, NP-dependent intracellular gene expression is essential for LCMV vector immunogenicity. PMID- 26355094 TI - A Highly Immunogenic and Protective Middle East Respiratory Syndrome Coronavirus Vaccine Based on a Recombinant Measles Virus Vaccine Platform. AB - In 2012, the first cases of infection with the Middle East respiratory syndrome coronavirus (MERS-CoV) were identified. Since then, more than 1,000 cases of MERS CoV infection have been confirmed; infection is typically associated with considerable morbidity and, in approximately 30% of cases, mortality. Currently, there is no protective vaccine available. Replication-competent recombinant measles virus (MV) expressing foreign antigens constitutes a promising tool to induce protective immunity against corresponding pathogens. Therefore, we generated MVs expressing the spike glycoprotein of MERS-CoV in its full-length (MERS-S) or a truncated, soluble variant of MERS-S (MERS-solS). The genes encoding MERS-S and MERS-solS were cloned into the vaccine strain MVvac2 genome, and the respective viruses were rescued (MVvac2-CoV-S and MVvac2-CoV-solS). These recombinant MVs were amplified and characterized at passages 3 and 10. The replication of MVvac2-CoV-S in Vero cells turned out to be comparable to that of the control virus MVvac2-GFP (encoding green fluorescent protein), while titers of MVvac2-CoV-solS were impaired approximately 3-fold. The genomic stability and expression of the inserted antigens were confirmed via sequencing of viral cDNA and immunoblot analysis. In vivo, immunization of type I interferon receptor deficient (IFNAR(-/-))-CD46Ge mice with 2 * 10(5) 50% tissue culture infective doses of MVvac2-CoV-S(H) or MVvac2-CoV-solS(H) in a prime-boost regimen induced robust levels of both MV- and MERS-CoV-neutralizing antibodies. Additionally, induction of specific T cells was demonstrated by T cell proliferation, antigen specific T cell cytotoxicity, and gamma interferon secretion after stimulation of splenocytes with MERS-CoV-S presented by murine dendritic cells. MERS-CoV challenge experiments indicated the protective capacity of these immune responses in vaccinated mice. IMPORTANCE: Although MERS-CoV has not yet acquired extensive distribution, being mainly confined to the Arabic and Korean peninsulas, it could adapt to spread more readily among humans and thereby become pandemic. Therefore, the development of a vaccine is mandatory. The integration of antigen-coding genes into recombinant MV resulting in coexpression of MV and foreign antigens can efficiently be achieved. Thus, in combination with the excellent safety profile of the MV vaccine, recombinant MV seems to constitute an ideal vaccine platform. The present study shows that a recombinant MV expressing MERS-S is genetically stable and induces strong humoral and cellular immunity against MERS CoV in vaccinated mice. Subsequent challenge experiments indicated protection of vaccinated animals, illustrating the potential of MV as a vaccine platform with the potential to target emerging infections, such as MERS-CoV. PMID- 26355097 TI - Characterization of the Determinants of NS2-3-Independent Virion Morphogenesis of Pestiviruses. AB - A peculiarity of the Flaviviridae is the critical function of nonstructural (NS) proteins for virus particle formation. For pestiviruses, like bovine viral diarrhea virus (BVDV), uncleaved NS2-3 represents an essential factor for virion morphogenesis, while NS3 is an essential component of the viral replicase. Accordingly, in natural pestivirus isolates, processing at the NS2-3 cleavage site is not complete, to allow for virion morphogenesis. Virion morphogenesis of the related hepatitis C virus (HCV) shows a major deviation from that of pestiviruses: while RNA replication also requires free NS3, virion formation does not depend on uncleaved NS2-NS3. Recently, we described a BVDV-1 chimera based on strain NCP7 encompassing the NS2-4B*-coding region of strain Osloss (E. Lattwein, O. Klemens, S. Schwindt, P. Becher, and N. Tautz, J Virol 86:427-437, 2012, doi:10.1128/JVI.06133-11). This chimera allowed for the production of infectious virus particles in the absence of uncleaved NS2-3. The Osloss sequence deviates in the NS2-4B* part from NCP7 in 48 amino acids and also has a ubiquitin insertion between NS2 and NS3. The present study demonstrates that in the NCP7 backbone, only two amino acid exchanges in NS2 (E1576V) and NS3 (V1721A) are sufficient and necessary to allow for efficient NS2-3-independent virion morphogenesis. The adaptation of a bicistronic virus encompassing an internal ribosomal entry site element between the NS2 and NS3 coding sequences to efficient virion morphogenesis led to the identification of additional amino acids in E2, NS2, and NS5B that are critically involved in this process. The surprisingly small requirements for approximating the packaging schemes of pestiviruses and HCV with respect to the NS2-3 region is in favor of a common mechanism in an ancestral virus. IMPORTANCE: For positive-strand RNA viruses, the processing products of the viral polyprotein serve in RNA replication as well as virion morphogenesis. For bovine viral diarrhea virus, nonstructural protein NS2 3 is of critical importance to switch between these processes. While free NS3 is essential for RNA replication, uncleaved NS2-3, which accumulates over time in the infected cell, is required for virion morphogenesis. In contrast, the virion morphogenesis of the related hepatitis C virus is independent from uncleaved NS2 NS3. Here, we demonstrate that pestiviruses can adapt to virion morphogenesis in the absence of uncleaved NS2-3 by just two amino acid exchanges. While the mechanism behind this gain of function remains elusive, the fact that it can be achieved by such minor changes is in line with the assumption that an ancestral virus already used this mechanism but lost it in the course of adapting to a new host/infection strategy. PMID- 26355096 TI - Ecuador Paraiso Escondido Virus, a New Flavivirus Isolated from New World Sand Flies in Ecuador, Is the First Representative of a Novel Clade in the Genus Flavivirus. AB - A new flavivirus, Ecuador Paraiso Escondido virus (EPEV), named after the village where it was discovered, was isolated from sand flies (Psathyromyia abonnenci, formerly Lutzomyia abonnenci) that are unique to the New World. This represents the first sand fly-borne flavivirus identified in the New World. EPEV exhibited a typical flavivirus genome organization. Nevertheless, the maximum pairwise amino acid sequence identity with currently recognized flaviviruses was 52.8%. Phylogenetic analysis of the complete coding sequence showed that EPEV represents a distinct clade which diverged from a lineage that was ancestral to the nonvectored flaviviruses Entebbe bat virus, Yokose virus, and Sokoluk virus and also the Aedes-associated mosquito-borne flaviviruses, which include yellow fever virus, Sepik virus, Saboya virus, and others. EPEV replicated in C6/36 mosquito cells, yielding high infectious titers, but failed to reproduce either in vertebrate cell lines (Vero, BHK, SW13, and XTC cells) or in suckling mouse brains. This surprising result, which appears to eliminate an association with vertebrate hosts in the life cycle of EPEV, is discussed in the context of the evolutionary origins of EPEV in the New World. IMPORTANCE: The flaviviruses are rarely (if ever) vectored by sand fly species, at least in the Old World. We have identified the first representative of a sand fly-associated flavivirus, Ecuador Paraiso Escondido virus (EPEV), in the New World. EPEV constitutes a novel clade according to current knowledge of the flaviviruses. Phylogenetic analysis of the virus genome showed that EPEV roots the Aedes-associated mosquito-borne flaviviruses, including yellow fever virus. In light of this new discovery, the New World origin of EPEV is discussed together with that of the other flaviviruses. PMID- 26355098 TI - Virus-Like Particle Vaccine Containing the F Protein of Respiratory Syncytial Virus Confers Protection without Pulmonary Disease by Modulating Specific Subsets of Dendritic Cells and Effector T Cells. AB - There is no licensed vaccine against respiratory syncytial virus (RSV) since the failure of formalin-inactivated RSV (FI-RSV) due to its vaccine-enhanced disease. We investigated immune correlates conferring protection without causing disease after intranasal immunization with virus-like particle vaccine containing the RSV fusion protein (F VLP) in comparison to FI-RSV and live RSV. Upon RSV challenge, FI-RSV immune mice showed severe weight loss, eosinophilia, and histopathology, and RSV reinfection also caused substantial RSV disease despite their viral clearance. In contrast, F VLP immune mice showed least weight loss and no sign of histopathology and eosinophilia. High levels of interleukin-4-positive (IL-4(+)) and tumor necrosis factor alpha-positive (TNF-alpha(+)) CD4(+) T cells were found in FI-RSV immune mice, whereas gamma interferon-positive (IFN-gamma(+)) and TNF alpha(+) CD4(+) T cells were predominantly detected in live RSV-infected mice. More importantly, in contrast to FI-RSV and live RSV that induced higher levels of CD11b(+) dendritic cells, F VLP immunization induced CD8alpha(+) and CD103(+) dendritic cells, as well as F-specific IFN-gamma(+) and TNF-alpha(+) CD8(+) T cells. These results suggest that F VLP can induce protection without causing pulmonary RSV disease by inducing RSV neutralizing antibodies, as well as modulating specific subsets of dendritic cells and CD8 T cell immunity. IMPORTANCE: It has been a difficult challenge to develop an effective and safe vaccine against respiratory syncytial virus (RSV), a leading cause of respiratory disease. Immune correlates conferring protection but preventing vaccine-enhanced disease remain poorly understood. RSV F virus-like particle (VLP) would be an efficient vaccine platform conferring protection. Here, we investigated the protective immune correlates without causing disease after intranasal immunization with RSV F VLP in comparison to FI-RSV and live RSV. In addition to inducing RSV neutralizing antibodies responsible for clearing lung viral loads, we show that modulation of specific subsets of dendritic cells and CD8 T cells producing T helper type 1 cytokines are important immune correlates conferring protection but not causing vaccine-enhanced disease. PMID- 26355099 TI - High-throughput sequencing and morphology perform equally well for benthic monitoring of marine ecosystems. AB - Environmental diversity surveys are crucial for the bioassessment of anthropogenic impacts on marine ecosystems. Traditional benthic monitoring relying on morphotaxonomic inventories of macrofaunal communities is expensive, time-consuming and expertise-demanding. High-throughput sequencing of environmental DNA barcodes (metabarcoding) offers an alternative to describe biological communities. However, whether the metabarcoding approach meets the quality standards of benthic monitoring remains to be tested. Here, we compared morphological and eDNA/RNA-based inventories of metazoans from samples collected at 10 stations around a fish farm in Scotland, including near-cage and distant zones. For each of 5 replicate samples per station, we sequenced the V4 region of the 18S rRNA gene using the Illumina technology. After filtering, we obtained 841,766 metazoan sequences clustered in 163 Operational Taxonomic Units (OTUs). We assigned the OTUs by combining local BLAST searches with phylogenetic analyses. We calculated two commonly used indices: the Infaunal Trophic Index and the AZTI Marine Biotic Index. We found that the molecular data faithfully reflect the morphology-based indices and provides an equivalent assessment of the impact associated with fish farms activities. We advocate that future benthic monitoring should integrate metabarcoding as a rapid and accurate tool for the evaluation of the quality of marine benthic ecosystems. PMID- 26355102 TI - Editorial. PMID- 26355100 TI - Protein Neighbors and Proximity Proteomics. AB - Within cells, proteins can co-assemble into functionally integrated and spatially restricted multicomponent complexes. Often, the affinities between individual proteins are relatively weak, and proteins within such clusters may interact only indirectly with many of their other protein neighbors. This makes proteomic characterization difficult using methods such as immunoprecipitation or cross linking. Recently, several groups have described the use of enzyme-catalyzed proximity labeling reagents that covalently tag the neighbors of a targeted protein with a small molecule such as fluorescein or biotin. The modified proteins can then be isolated by standard pulldown methods and identified by mass spectrometry. Here we will describe the techniques as well as their similarities and differences. We discuss their applications both to study protein assemblies and to provide a new way for characterizing organelle proteomes. We stress the importance of proteomic quantitation and independent target validation in such experiments. Furthermore, we suggest that there are biophysical and cell biological principles that dictate the appropriateness of enzyme-catalyzed proximity labeling methods to address particular biological questions of interest. PMID- 26355101 TI - Characteristic Changes in Cell Surface Glycosylation Accompany Intestinal Epithelial Cell (IEC) Differentiation: High Mannose Structures Dominate the Cell Surface Glycome of Undifferentiated Enterocytes. AB - Changes in cell surface glycosylation occur during the development and differentiation of cells and have been widely correlated with the progression of several diseases. Because of their structural diversity and sensitivity to intra- and extracellular conditions, glycans are an indispensable tool for analyzing cellular transformations. Glycans present on the surface of intestinal epithelial cells (IEC) mediate interactions with billions of native microorganisms, which continuously populate the mammalian gut. A distinct feature of IECs is that they differentiate as they migrate upwards from the crypt base to the villus tip. In this study, nano-LC/ESI QTOF MS profiling was used to characterize the changes in glycosylation that correspond to Caco-2 cell differentiation. As Caco-2 cells differentiate to form a brush border membrane, a decrease in high mannose type glycans and a concurrent increase in fucosylated and sialylated complex/hybrid type glycans were observed. At day 21, when cells appear to be completely differentiated, remodeling of the cell surface glycome ceases. Differential expression of glycans during IEC maturation appears to play a key functional role in regulating the membrane-associated hydrolases and contributes to the mucosal surface innate defense mechanisms. Developing methodologies to rapidly identify changes in IEC surface glycans may lead to a rapid screening approach for a variety of disease states affecting the GI tract. PMID- 26355103 TI - Half of women over 70 unable to name non-lump symptoms of breast cancer. PMID- 26355104 TI - Report shows urgent need for new tobacco strategy. PMID- 26355105 TI - Sport and arts - important settings for health improvement. PMID- 26355106 TI - NICE guidance reflected in IHM Professional Practice Framework. PMID- 26355107 TI - Workplace culture that promotes health and wellbeing for all: an imperative for health care managers and others. PMID- 26355108 TI - Healthcare management and leadership. PMID- 26355109 TI - Encouraging a culture of greater collaboration. PMID- 26355110 TI - Culture health and wellbeing: a health systems cultural barometer for healthcare managers. PMID- 26355111 TI - Integrated health and social care: a personal reflection on frontline services. PMID- 26355112 TI - Commissioners can do more to reduce variations in care. PMID- 26355115 TI - A mass shooting at Port Arthur, Tasmania, Australia: a study of its impact on early pregnancy losses using a conception time-based methodology. AB - STUDY QUESTION: Does an acute calamity in a community cause early miscarriage and is this association the same for male and female fetuses? SUMMARY ANSWER: Estimated losses of 29.5% of first trimester pregnancies in the affected region could be associated with an acute calamity, with no statistically significant difference in estimated losses by fetal sex. WHAT IS KNOWN ALREADY: There are very few studies on the impact of a calamity on early pregnancy loss and its differential effects on male and female fetuses. A decline in the human sex ratio at birth associated with the events of 9/11 in New York has been documented. STUDY DESIGN, SIZE, DURATION: This is a retrospective descriptive study of birth register data in Tasmania, Australia, from 1991 to 1997, covering the period in which the calamity occurred. The register contains data on all pregnancies that proceeded to >20 weeks gestation. The conception date was calculated by subtracting gestational age from birth date. We estimated that 40 318 pregnancies were conceived in the period 1991-1996 inclusive. These were aggregated to 4 weekly blocks classified by region and sex. PARTICIPANTS/MATERIALS, SETTING, METHODS: The acute calamity was at Port Arthur, Tasmania, Australia. On 28 April 1996, a gunman opened fire on visitors and staff in a tourist cafe. A very stressful 20 h period, ended with 35 people dead and 22 injured. A negative binomial regression model was used to assess the association between this calamity and pregnancy loss. This loss is evidenced by a shortfall in the registration of pregnancies that were in their first trimester at the time of the calamity. MAIN RESULTS AND THE ROLE OF CHANCE: We estimated a shortfall of 29.5% or 229 registered pregnancies among those in the first trimester at the time of the calamity (P < 0.001), in the region surrounding the calamity site. There was no sex effect in this shortfall (P = 0.911). There was no corresponding shortfall in other parts of Tasmania (P = 0.349). LIMITATIONS, REASONS FOR CAUTION: The study is descriptive and cannot produce causal inferences. These first trimester miscarriages are estimated statistically and it is understood that gestational age is an estimate. The use of maternal residential postcodes at birth as a surrogate for geographic area or space assumes that the mother has not moved into the postcode area after the calamity and before the reporting of a birth. WIDER IMPLICATIONS OF THE FINDINGS: The results of this study suggest that calamities bring about significant pregnancy loss affecting both sexes. The methodology presented of inferring conception date from birth date and using this for analysis, provides a more accurate assessment of first trimester pregnancy losses than raw birth data or sex ratio at birth. PMID- 26355116 TI - Collapse of blastocysts is strongly related to lower implantation success: a time lapse study. AB - STUDY QUESTION: Is there an association between blastocyst collapse patterns and implantation potential? SUMMARY ANSWER: Embryos that exhibit collapse are as likely to hatch as those that do not, but are less likely to implant and should not be replaced if alternatives are available. WHAT IS KNOWN ALREADY: Studies of blastocyst collapse in different species of mammals have found that most blastocysts, that experience consecutive weak contractions, hatch successfully whereas those that exhibit strong contractions or collapse, fail to hatch. STUDY DESIGN, SIZE, DURATION: Retrospective cohort study. Seven hundred and fifteen transferred blastocysts were analyzed from July 2012 to May 2013. PARTICIPANTS/MATERIALS, SETTING, METHODS: University-affiliated infertility center. Participant patients were recipients of oocyte donation and autologous IVF cycles (n = 460). Embryo development was analyzed with a time-lapse imaging system. Variables studied included blastocyst collapse (defined as the separation of >=50% of the surface of the trophectoderm of the blastocyst from the zona pellucida), kinetic variables, embryo morphology, implantation and clinical pregnancy rates. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 139 blastocysts presented collapse (19.4%), of these 8 presented 2 collapses and 2 presented 3 collapses. The timings of embryo cleavages and the time taken to reach the morula stage and blastulation were significantly shorter in embryos with collapse than in those without. Implantation rates were compared in cycles where either all or none of the embryos replaced, implanted so that implantation data were known for every embryo. Among 408 embryos without collapse and 94 embryos with at least one collapse (94) the implantation rates were 48.5% (95% confidence intervals (CI) 46.7-53.4%) and 35% (95% CI 25.3-44.9%), respectively. The percentage of embryos that hatched was similar in both groups 28.7 and 31%, respectively. LIMITATIONS, REASONS FOR CAUTION: The retrospective nature of the study limits its potential value. WIDER IMPLICATIONS OF THE FINDINGS: Study the collapse pattern of the blastocyst, may assist selection of the blastocysts most likely to implant and increase IVF/ICSI success rates. PMID- 26355117 TI - Plasma Levels of the Cerebral Biomarker, Neuron-Specific Enolase, are Elevated During Pregnancy in Women Developing Preeclampsia. AB - OBJECTIVES: Neuron-specific enolase (NSE) is considered to be a peripheral biomarker of central nervous system injury. The aim of this study was to compare levels of NSE throughout pregnancy, in healthy pregnant women and in women developing preeclampsia. METHODS: A nested case-control study within a longitudinal study cohort was performed. Four hundred sixty nine healthy pregnant women were enrolled, and plasma samples were collected at gestational weeks 10, 25, 28, 33, and 37. Levels of NSE were analyzed in 16 women with preeclampsia and 36 controls throughout pregnancy with an enzyme-linked immunosorbent assay. RESULTS: In gestational week 37, women who developed preeclampsia had significantly higher plasma levels of NSE than healthy pregnant controls (P < .001). The levels of NSE did not change between gestational weeks 10 and 37 in women who developed preeclampsia, but the levels decreased significantly in healthy pregnant controls (P < .001). CONCLUSION: In pregnant women developing preeclampsia, the levels of NSE remained high throughout pregnancy, whereas in healthy women, these tended to decline over time, especially at the 2 last time points. The result might be confounded in early pregnancy by extracerebral sources of NSE, such as the corpus luteum. Findings need to be confirmed in a larger prospective study. PMID- 26355118 TI - Urinary Excretion of Myo-Inositol and D-Chiro-Inositol in Early Pregnancy Is Enhanced in Gravidas With Gestational Diabetes Mellitus. AB - The effects of gestational diabetes mellitus (GDM) were determined on urinary excretion of putative components of insulin signaling. Random urine samples were collected from 375 gravidas at 6 to 14 weeks' gestation, 22 to 32 weeks' gestation, and ~6 weeks' postpartum. Gestational diabetes mellitus developed in 35 women who were matched with 59 normal gravidas. Urinary concentrations of myo inositol (MI) and D-chiro-inositol (DCI) were measured by gas chromatography/mass spectrometry and normalized to creatinine levels. Compared to postpartum values, urinary excretion of MI and DCI was increased 2.9-fold and 2-fold, respectively, in early pregnancy, and 5.5-fold and 4.5-fold, respectively, in later gestation. Gravidas with GDM had significantly greater MI and DCI excretion than controls in the first trimester but not subsequently. The results suggest that gravidas destined to develop GDM have altered synthesis, metabolism, and/or renal excretion of MI and DCI in early pregnancy. PMID- 26355119 TI - Lower extremity musculoskeletal disorders in nurses: A narrative literature review. AB - AIMS: The aim of the narrative review was to describe and analyze lower extremity musculoskeletal disorders (MSDs) in nurses and to identify factors associated with these disorders. The ultimate goal was to promote lower extremity health in nurses by recognizing factors that could improve their well-being at work. METHODS: A systematic search on the Medline, CINAHL, and PsychInfo databases was conducted, producing altogether 945 citations, of which 35 were selected for this review. The studies were analyzed by content analysis. RESULTS: Nurses have different MSDs in their lower extremities, with which the knee, foot, and ankle being most commonly affected. These problems are often correlated, and problems in the ankle can first appear as knee problems. CONCLUSIONS: Musculoskeletal disorders in lower extremities and their resulting disability are common within the nursing workforce worldwide, representing a major cause of sick leave absence and often leading to long-term absence. PMID- 26355120 TI - Colon cancer trends in Norway and Denmark by socio-economic group: A cohort study. AB - AIMS: Norway has experienced an unprecedented rapid and so far unexplained increase in colon cancer incidence. Norwegian rates passed Danish rates for men in 1985 and for women in 1990. This study aimed to unravel clues to the development in colon cancer incidence by investigating changes over time in incidence by socio-economic group. METHODS: Persons participating in the 1970 censuses in Norway and Denmark were aged 55-75 years in 1971-1980 (called pre crossing period) and in 1991-2000 (called post-crossing period), respectively. Country, sex, age and socio-economic group-specific colon cancer incidence rates. Percent change in the average rate from the pre- to the post-crossing period. RESULTS: In the pre-crossing period, Norwegian male managers/administrators had the highest colon cancer incidence, but the largest increase in incidence from the pre-to the post-crossing period was seen for unskilled workers, skilled workers and farmers. The rate for unskilled workers almost doubled and in the post-crossing period this rate had bypassed that of managers/administrators. A similar development was seen for Norwegian women and was less dramatic in Denmark. CONCLUSIONS: The change in the risk of manual workers has been the driving force behind the dramatic increase in the Norwegian incidence of colon cancer. This development resulted in a reversal of the socio-economic gradient from the classic European pattern with the highest incidence in the upper socio economic groups to an American pattern with the highest incidence in the lower socio-economic groups. This 'Americanization' of the disease pattern followed the rapid growth in the Norwegian gross domestic product. PMID- 26355122 TI - Defining thresholds for home blood pressure monitoring in octogenarians. AB - To generate outcome-driven thresholds for home blood pressure (BP) in the elderly, we analyzed 375 octogenarians (60.3% women; 83.0 years [mean]) enrolled in the International Database on home BP in relation to cardiovascular outcome. Over 5.5 years (median), 155 participants died, 76 from cardiovascular causes, whereas 104, 55, 36, and 51 experienced a cardiovascular, cardiac, coronary, or cerebrovascular event, respectively. In 202 untreated participants, home diastolic in the lowest fifth of the distribution (<=65.1 mm Hg) compared with the multivariable-adjusted average risk was associated with increased risk of cardiovascular mortality and morbidity (hazard ratios [HRs], >=1.96; P<=0.022), whereas the HR for cardiovascular mortality in the top fifth (>=82.0 mm Hg) was 0.37 (P=0.034). Among 173 participants treated for hypertension, the HR for total mortality in the lowest fifth of systolic home BP (<126.9 mm Hg) was 2.09 (P=0.020). In further analyses of home BP as continuous variable (per 1-SD increment), higher diastolic BP predicted lower cardiovascular mortality and morbidity and cardiac and coronary risk (HR<=0.65; P<=0.039) in untreated participants. In those treated, cardiovascular morbidity was curvilinearly associated with systolic home BP with nadir at 148.6 mm Hg and with a 1.45 HR (P=0.046) for a 1-SD decrease below this threshold. In conclusion, in untreated octogenarians, systolic home BP >=152.4 and diastolic BP <=65.1 mm Hg entails increased cardiovascular risk, whereas diastolic home BP >=82 mm Hg minimizes risk. In those treated, systolic home BP <126.9 mm Hg was associated with increased total mortality with lowest risk at 148.6 mm Hg. PMID- 26355123 TI - On the influence of an equatorial cerclage on closure of posterior retinal detachment. AB - A mechanics-based mathematical model of an eye possessing a posterior retinal detachment is presented for the case where an encircling scleral buckle (a cerclage) is sutured around the equator of the eye. The mechanical behaviour of the retina and the globe, both before and after applying the cerclage, is studied. An energy formulation yields the self-consistent equations of equilibrium and boundary conditions of the ocular system, and analytical solutions are established for the scleral buckle, for the globe and for the detached segment of the retina. Results of numerical simulations based on the solutions unveil characteristic behaviour of the ocular system, and demonstrate the influence of the scleral buckle, as well as of the pressure difference between the vitreous cavity and the subretinal space, on the deformation of the eye and on closing the region of retinal detachment. The results indicate that a scleral buckle encircling the equator, normally used for closing retinal tears and associated retinal detachments in the immediate vicinity of the buckle, can have a marked influence on bringing the detached segment of neurosensory retina back into contact with the retinal pigment epithelium, even for detachments at the posterior of the eye. PMID- 26355124 TI - Practice-based Research Networks (PBRNs) in the United States: Growing and Still Going After All These Years. PMID- 26355125 TI - The Most Frequently Read Practice-based Research (PBR) Articles in the Journal of the American Board of Family Medicine (JABFM). PMID- 26355126 TI - Success in the Achieving CARdiovascular Excellence in Colorado (A CARE) Home Blood Pressure Monitoring Program: A Report from the Shared Networks of Colorado Ambulatory Practices and Partners (SNOCAP). AB - BACKGROUND: Blood pressure (BP) control among primary care patients with hypertension is suboptimal. Home BP monitoring (HBPM) has been shown to be effective but is underused. METHODS: This study was a quasi-experimental evaluation of the impact of the A CARE HBPM program on hypertension control. Nonpregnant adults with hypertension or cardiovascular disease risk factors were given validated home BP monitors and reported monthly average home BP readings by Internet or phone. Patients and providers received feedback. Change in average home and office BP and the percentage of patients achieving target BP were assessed based on patient HBPM reports and a chart audit of office BPs. RESULTS: A total of 3578 patients were enrolled at 26 urban and rural primary care practices. Of these, 36% of participants submitted >=2 HBPM reports. These active participants submitted a mean of 13.5 average HBPM reports, with a mean of 19.3 BP readings per report. The mean difference in home BP between initial and final HBPM reports for active participants was -6.5/-4.4 mmHg (P < .001) and -6.7/-4.7 mmHg (P < .001) for those with diabetes. The percentage of active participants at or below target BP increased from 34.5% to 53.3% (P < .001) and increased 24.6% to 40.0% (P < .001) for those with diabetes. The mean difference in office BP over 1 year between participants and nonparticipants was -5.4/-2.7 mmHg (P < .001 for systolic BP, P = .01 for diastolic BP) for all participants and -8.5/-1.5 mmHg (P = .014 for systolic BP, P = .405 for diastolic BP) for those with diabetes. CONCLUSIONS: An HBPM program with patient and provider feedback can be successfully implemented in a range of primary care practices and can play a significant role in BP control and decreased cardiovascular disease risk in patients with hypertension. PMID- 26355127 TI - Lessons for Primary Care from the First Ten Years of Medicare Coordinated Care Demonstration Projects. AB - Over the past decade, Medicare has tested care coordination programs in an effort to achieve the triple aim of improving the patient experience, improving population health, and lowering costs. Although savings from this promising concept have not materialized, private payers are starting to offer blended payments to primary care. From these demonstrations, we propose 5 lessons for practices implementing care coordination: (1) minimize expenses by sharing resources and avoiding cost ineffective interventions; (2) concentrate on high utilizers; (3) foster relationships with both providers and patients; (4) track patients across the medical neighborhood in real time; and (5) extend rather than a duplicate the efforts of primary care practices. PMID- 26355128 TI - Accelerated Adoption of Advanced Health Information Technology in Beacon Community Health Centers. AB - BACKGROUND: To complement national and state-level HITECH Act programs, 17 Beacon communities were funded to fuel community-wide use of health information technology to improve quality. Health centers in Beacon communities received supplemental funding. METHODS: This article explores the association between participation in the Beacon program and the adoption of electronic health records. Using the 2010-2012 Uniform Data System, trends in health information technology adoption among health centers located within and outside of Beacon communities were explored using differences in mean t tests and multivariate logistic regression. RESULTS: Electronic health record adoption was widespread and rapidly growing in all health centers, especially quality improvement functionalities: structured data capture, order and results management, and clinical decision support. Adoption lagged for functionalities supporting patient engagement, performance measurement, care coordination, and public health. The use of advanced functionalities such as care coordination grew faster in Beacon health centers, and Beacon health centers had 1.7 times higher odds of adopting health records with basic safety and quality functionalities in 2010-2012. DISCUSSION: Three factors likely underlie these findings: technical assistance, community-wide activation supporting health information exchange, and the layering of financial incentives. Additional technical assistance and community wide activation is needed to support the use of functionalities that are currently lagging. PMID- 26355129 TI - Launching a Laboratory Testing Process Quality Improvement Toolkit: From the Shared Networks of Colorado Ambulatory Practices and Partners (SNOCAP). AB - INTRODUCTION: Family medicine and internal medicine physicians order diagnostic laboratory tests for nearly one-third of patient encounters in an average week, yet among medical errors in primary care, an estimated 15% to 54% are attributed to laboratory testing processes. From a practice improvement perspective, we (1) describe the need for laboratory testing process quality improvements from the perspective of primary care practices, and (2) describe the approaches and resources needed to implement laboratory testing process quality improvements in practice. METHODS: We applied practice observations, process mapping, and interviews with primary care practices in the Shared Networks of Colorado Ambulatory Practices and Partners (SNOCAP)-affiliated practice-based research networks that field-tested in 2013 a laboratory testing process improvement toolkit. RESULTS: From the data collected in each of the 22 participating practices, common testing quality issues included, but were not limited to, 3 main testing process steps: laboratory test preparation, test tracking, and patient notification. Three overarching qualitative themes emerged: practices readily acknowledge multiple laboratory testing process problems; practices know that they need help addressing the issues; and practices face challenges with finding patient-centered solutions compatible with practice priorities and available resources. CONCLUSION: While practices were able to get started with guidance and a toolkit to improve laboratory testing processes, most did not seem able to achieve their quality improvement aims unassisted. Providing specific guidance tools with practice facilitation or other rapid-cycle quality improvement support may be an effective approach to improve common laboratory testing issues in primary care. PMID- 26355131 TI - Rural Clinician Evaluation of Children's Health Care Quality Measures: An Oregon Rural Practice-based Research Network (ORPRN) Study. AB - BACKGROUND: Responding to quality metrics is an accepted and expected component of the current health care environment. Little is known about which measures physicians identify as a priority when reporting the quality of care to their patients, especially the care of children in rural settings. The objective of this study is for physicians caring for children in rural communities to identify which of the initial core sets of 24 child health quality measures are useful and are a priority for reporting and improving care. METHODS: A survey was sent to rural Oregon physicians who provide care to children. RESULTS: Of 955 eligible physicians, 172 (18%) completed the survey. The majority of respondents were family physicians (84%), and most respondents (58%) were in private practice. The child health measures stratified into 3 priority tiers: high, medium, and low priority. The top-tier priority measures included childhood immunization status, well-child visits, adolescent immunization status, body mass index assessment, and developmental screening. Dental treatment services, adequate prenatal care, and lower-birth-weight infants were among the lower-tier measures. CONCLUSIONS: The priority measures identified by rural family physicians reflect the relevance of the selected measures to their daily practice responsibilities, with missed opportunities to improve community health. PMID- 26355130 TI - Do Subjective Measures Improve the Ability to Identify Limited Health Literacy in a Clinical Setting? AB - BACKGROUND: Existing health literacy assessments developed for research purposes have constraints that limit their utility for clinical practice, including time requirements and administration protocols. The Brief Health Literacy Screen (BHLS) consists of 3 self-administered Single-Item Literacy Screener (SILS) questions and obviates these clinical barriers. We assessed whether the addition of SILS items or the BHLS to patient demographics readily available in ambulatory clinical settings reaching underserved patients improves the ability to identify limited health literacy. METHODS: We analyzed data from 2 cross-sectional convenience samples of patients from an urban academic emergency department (n = 425) and a primary care clinic (n = 486) in St. Louis, Missouri. Across samples, health literacy was assessed using the Rapid Estimate of Adult Literacy in Medicine-Revised (REALM-R), Newest Vital Sign (NVS), and the BHLS. Our analytic sample consisted of 911 adult patients, who were primarily female (62%), black (66%), and had at least a high school education (82%); 456 were randomly assigned to the estimation sample and 455 to the validation sample. RESULTS: The analysis showed that the best REALM-R estimation model contained age, sex, education, race, and 1 SILS item (difficulty understanding written information). In validation analysis this model had a sensitivity of 62%, specificity of 81%, a positive likelihood ratio (LR(+)) of 3.26, and a negative likelihood ratio (LR( )) of 0.47; there was a 28% misclassification rate. The best NVS estimation model contained the BHLS, age, sex, education and race; this model had a sensitivity of 77%, specificity of 72%, LR(+) of 2.75, LR(-) of 0.32, and a misclassification rate of 25%. CONCLUSIONS: Findings suggest that the BHLS and SILS items improve the ability to identify patients with limited health literacy compared with demographic predictors alone. However, despite being easier to administer in clinical settings, subjective estimates of health literacy have misclassification rates >20% and do not replace objective measures; universal precautions should be used with all patients. PMID- 26355133 TI - Radon Testing: Community Engagement By a Rural Family Medicine Office. AB - OBJECTIVE: Iowa has the highest average radon concentrations in the nation, with an estimated 400 radon-induced lung cancer deaths each year. Radon is the second leading cause of lung cancer death overall. The objectives of this study were (1) to educate the population attending a family medicine office about the dangers of radon, (2) to encourage homeowners to test for radon, (3) to work with the community to identify resources for mitigation, and (4) to assess the utility of working with a local family medicine office as a model that could be adopted for other communities with high home radon concentrations. METHODS: Participants obtained a US Environmental Protection Agency-certified activated charcoal short term radon kit through their primary care office or by attending a seminar held by their medical office. Participants completed a short investigator-developed questionnaire about their home, heating, and demographics. RESULTS: Of 746 radon kits handed out, 378 valid results (51%) were received, of which 351 questionnaires could be matched to the kit results. The mean radon result was 10.0 pCi/L (standard deviation, 8.5 pCi/L). A radon result of 4 pCi/L or higher, the Environmental Protection Agency action level for mitigation, was found in 81% of homes (n = 285). CONCLUSIONS: Four of 5 homes tested had elevated radon levels. This family medicine office/university collaborative educational model could be useful for educating patients about other environmental dangers. PMID- 26355132 TI - Clinical Needs of Patients with Problem Drug Use. AB - INTRODUCTION: Illicit drug use is a serious public health problem associated with significant co-occurring medical disorders, mental disorders, and social problems. Yet most individuals with drug use disorders have never been treated, though they often seek medical treatment in primary care. The purpose of this study was to examine the baseline characteristics of people presenting in primary care with a range of problem drug use severity to identify their clinical needs. METHODS: We examined sociodemographic characteristics, medical and psychiatric comorbidities, drug use severity, social and legal problems, and service utilization for 868 patients with drug problems. These patients were recruited from primary care clinics in a medical safety net setting. Based on Drug Abuse Screening Test results, individuals were categorized as having low, intermediate, or substantial/severe drug use severity. RESULTS: Patients with substantial/severe drug use severity had serious drug use (opiates, stimulants, sedatives, intravenous drugs); high levels of homelessness (50%), psychiatric comorbidity (69%), and arrests for serious crimes (24%); and frequent use of expensive emergency department and inpatient hospitals. Patients with low drug use severity were primarily users of marijuana, with little reported use of other drugs, less psychiatric comorbidity, and more stable lifestyles. Patients with intermediate drug use severity fell in between the substantial/severe and low drug use severity subgroups on most variables. CONCLUSIONS: Patients with the highest drug use severity are likely to require specialized psychiatric and substance abuse care, in addition to ongoing medical care that is equipped to address the consequences of severe/substantial drug use, including intravenous drug use. Because of their milder symptoms, patients with low drug use severity may benefit from a collaborative care model that integrates psychiatric and substance abuse care in the primary care setting. Patients with intermediate drug use severity may benefit from selective application of interventions suggested for patients with the highest and lowest drug use severity. Primary care safety net clinics are in a key position to serve patients with problem drug use by developing a range of responses that are locally effective and that may also inform national efforts to establish patient-centered medical homes and to implement the Affordable Care Act. PMID- 26355134 TI - Chronic Kidney Disease Guideline Implementation in Primary Care: A Qualitative Report from the TRANSLATE CKD Study. AB - BACKGROUND: Primary care physicians (PCPs) are optimally situated to identify and manage early stage chronic kidney disease (CKD). Nonetheless, studies have documented suboptimal PCP understanding, awareness, and management of early CKD. The TRANSLATE CKD study is an ongoing national, mixed-methods, cluster randomized control trial that examines the implementation of evidence-based guidelines for CKD into primary care practice. METHODS: As part of the mixed-methods process evaluation, semistructured interviews were conducted by phone with 27 providers participating in the study. Interviews were audio-taped and transcribed. Thematic content analysis was used to identify themes. Themes were categorized according to the 4 domains of Normalization Process Theory (NPT). RESULTS: Identified themes illuminated the complex work undertaken to manage CKD in primary care practices. Barriers to guideline implementation were identified in each of the 4 NPT domains, including (1) lack of knowledge and understanding around CKD (coherence), (2) difficulties engaging providers and patients in CKD management (cognitive participation), (3) limited time and competing demands (collective action), and (4) challenges obtaining and using data to monitor progress (reflexive monitoring). CONCLUSIONS: Addressing the barriers to implementation with concrete interventions at the levels at which they occur, informed by NPT, will ultimately improve the quality of CKD patient care. PMID- 26355135 TI - Lessons Learned from Developing a Patient Engagement Panel: An OCHIN Report. AB - There is renewed interest in patient engagement in clinical and research settings, creating a need for documenting and publishing lessons learned from efforts to meaningfully engage patients. This article describes early lessons learned from the development of OCHIN's Patient Engagement Panel (PEP). OCHIN supports a national network of more than 300 community health centers (CHCs) and other primary care settings that serve over 1.5 million patients annually across nearly 20 states. The PEP was conceived in 2009 to harness the CHC tradition of patient engagement in this new era of patient-centered outcomes research and to ensure that patients were engaged throughout the life cycle of our research projects, from conception to dissemination. Developed by clinicians and researchers within our practice-based research network, recruitment of patients to serve as PEP members began in early 2012. The PEP currently has a membership of 18 patients from 3 states. Over the past 24 months, the PEP has been involved with 12 projects. We describe developing the PEP and challenges and lessons learned (eg, recruitment, funding model, creating value for patient partners, compensation). These lessons learned are relevant not only for research but also for patient engagement in quality improvement efforts and other clinical initiatives. PMID- 26355136 TI - Clinician and Staff Perspectives on Participating in Practice-based Research (PBR): A Report from the Wisconsin Research and Education Network (WREN). AB - BACKGROUND: The success of practice-based research (PBR) depends on the willingness of clinicians and staff to incorporate meaningful and useful research protocols into already demanding clinic schedules. The impact of participation on those who implement multiple projects and how to address the issues that arise during this complex process remain incompletely described. This article reports a qualitative evaluation of the experiences of primary care clinicians and clinic staff who participated in multiple PBR projects with the Wisconsin Research and Education Network (WREN). Also included are their suggestions to researchers and clinicians for future collaborations. METHODS: For program evaluation purposes, WREN conducted 4 focus groups at its 2014 annual meeting. The main focus group question was, "How has participation in PBR affected you and your clinic?" A total of 27 project members from 13 clinics participated in 4 groups (physicians, nurses, managers, and other clinical staff). The 2-hour sessions were recorded, transcribed, and analyzed to identify recurring themes. RESULTS: Five major focus group themes emerged: receptivity to research, outcomes as a result of participation, barriers to implementation, facilitators of success, and advice to researchers and colleagues. Focus group members find research valuable and enjoy participating in projects that are relevant to their practice, even though many barriers exist. They indicated that research participation produces clinical changes that they believe result in improved patient care. They offered ways to improve the research process, with particular emphasis on collaborative early planning, project development, and communication before, during, and after a project. CONCLUSIONS: Clinics that participate in WREN projects remain willing to risk potential work constraints because of immediate or impending benefits to their clinical practice and/or patient population. Including a broader array of clinic personnel in the communication processes, especially in the development of relevant research ideas and planning for clinic implementation and ongoing participation in research projects, would address many of the barriers identified in implementing PBR. The themes and supporting quotes identified in this evaluation of WREN projects may inform researchers planning to collaborate with primary care clinics and clinicians and staff considering participating in research endeavors. PMID- 26355137 TI - Lessons from Initiating the First Veterans Health Administration (VA) Women's Health Practice-based Research Network (WH-PBRN) Study. AB - BACKGROUND: The Veterans Health Administration (VA) Women's Health Practice-Based Research Network (WH-PBRN) was created to foster innovations for the health care of women veterans. The inaugural study by the WH-PBRN was designed to identify women veterans' own priorities and preferences for mental health services and to inform refinements to WH-PBRN operational procedures. Addressing the latter, this article reports lessons learned from the inaugural study. METHODS: WH-PBRN site coordinators at the 4 participating sites convened weekly with the study coordinator and the WH-PBRN program manager to address logistical issues and identify lessons learned. Findings were categorized into a matrix of challenges and facilitators related to key study elements. RESULTS: Challenges to the conduct of PBRN-based research included tracking of regulatory documents; cross site variability in some regulatory processes; and troubleshooting logistics of clinic-based recruitment. Facilitators included a central institutional review board, strong relationships between WH-PBRN research teams and women's health clinic teams, and the perception that women want to help other women veterans. CONCLUSION: Our experience with the inaugural WH-PBRN study demonstrated the feasibility of establishing productive relationships between local clinicians and researchers, and of recruiting a special population (women veterans) in diverse sites within an integrated health care system. This identified strengths of a PBRN approach. PMID- 26355138 TI - Practice-based Research Networks (PBRNs) in the Era of Integrated Delivery Systems. AB - Practice-based research networks (PBRNs) have been in existence for several decades, and they provide one mechanism to conduct research outside of academic research centers. Two transformative changes to the practice environment pose significant challenges to the manner in which PBRNs have functioned in the past and require changes to their current activities. The widespread introduction of electronic health records and the organization of practices into often hospital dominated integrated delivery systems change the manner in which medicine is practiced, administered, and financed. Research funders are committed to extending research into communities, although we have yet to learn how to conduct these activities efficiently. We describe a number of operational challenges to this transformation, and we also propose ways to address these challenges and improve the quality and efficiency through which research is conducted. PBRNs can ensure their relevance in the research environment by adapting to this new era. PMID- 26355139 TI - Pragmatic Cluster Randomized Trials Using Covariate Constrained Randomization: A Method for Practice-based Research Networks (PBRNs). AB - BACKGROUND: Cluster randomized trials (CRTs) are useful in practice-based research network translational research. However, simple or stratified randomization often yields study groups that differ on key baseline variables when the number of clusters is small. Unbalanced study arms constitute a potentially serious methodological problem for CRTs. METHODS: Covariate constrained randomization with data on relevant variables before randomization was used to achieve balanced study arms in 2 pragmatic CRTs. In study 1, 16 counties in Colorado were randomized to practice-based or population-based reminder recall for vaccinating children ages 19 to 35 months. In study 2, 18 primary care practices were randomized to computer decision support plus practice facilitation versus computer decision support alone to improve care for patients with stage 3 and 4 chronic kidney disease. For each study, a set of optimal randomizations, which minimized differences of key variables between study arms, was identified from the set of all possible randomizations. RESULTS: Differences between study arms were smaller in the optimal versus remaining randomizations. Even for the randomization in the optimal set with the largest difference between groups, study arms did not differ significantly on any variable for either study (P > .05). CONCLUSIONS: Covariate constrained randomization, which restricts the full randomization set to a subset in which differences between study arms are minimized, is a useful tool for achieving balanced study arms in CRTs. Because of the increasing recognition of the risk of imbalance in CRTs and implications for interpreting study findings, procedures of this type should be considered in designing practice-based or community-based trials. PMID- 26355140 TI - Establishment of a Representative Practice-based Research Network (PBRN) for the Monitoring of Primary Care in Switzerland. AB - Data are urgently needed to better understand processes of care in Swiss primary care (PC). A total of 2027 PC physicians, stratified by canton, were invited to participate in the Swiss Primary care Active Monitoring network, of whom 200 accepted to join. There were no significant differences between participants and a random sample drawn from the same physician databases based on sex, year of obtaining medical school diploma, or location. The Swiss Primary care Active Monitoring network represents the first large-scale, nationally representative practice-based research network in Switzerland and will provide a unique opportunity to better understand the functioning of Swiss PC. PMID- 26355141 TI - Using Shared Medical Appointments to Increase Access to Buprenorphine Treatment. AB - INTRODUCTION: This study examines patient experiences with shared medical appointments for buprenorphine treatment at a safety net primary care clinic. METHODS: This is a cross-sectional observational study of 28 participants in a primary care buprenorphine shared medical appointments program. RESULTS: Participants reported appreciating the group visit format, gaining increased coping skills, and having more stable housing and less legal difficulty after starting the program. CONCLUSION: The implementation of shared medical appointments for buprenorphine treatment benefits clinicians and patients. The nurse care manager and buprenorphine prescriber can efficiently attend to the clinical needs of multiple patients. PMID- 26355142 TI - Inaccuracy of ICD-9 Codes for Chronic Kidney Disease: A Study from Two Practice based Research Networks (PBRNs). AB - BACKGROUND: Inaccurate use of International Classification of Diseases, Ninth Revision (ICD-9), codes obfuscates registries used for research, resulting in unreliable data and inaccurate measurement of outcomes, and it may contribute to mismanagement of patients. Thus it is important to understand the prevalence of ICD-9 code misuse. We chose chronic kidney disease (CKD) as a condition of interest after several patients recruited for a previous study indicated they did not have the disease, despite the presence of the ICD-9 code (585.x) in their electronic medical record (EMR). METHODS: Retrospective chart review of patients with the ICD-9 code for CKD stage 3 (585.3; n = 325). Data were collected from EMRs at 3 primary care practices Buffalo, New York (n = 2), and Kansas City, Kansas (n = 1). RESULTS: Across all practices, 47% of patients with the CKD ICD-9 code did not have clinical indicators for the disease, based on Kidney Disease Outcomes Quality Initiative guidelines. CONCLUSIONS: The CKD stage 3 ICD-9 code usage did not accurately reflect the prevalence of disease among this population. This has clinical implications because patients may be treated or receive tests for a disease they do not have. This also presents an important issue for research projects that rely on accurate data from EMRs to identify and recruit patients. PMID- 26355143 TI - Re: Magnesium Intake and Depression in Adults. PMID- 26355144 TI - Re: The Use of Medical Scribes in Health Care Settings: A Systematic Review and Future Directions. PMID- 26355145 TI - ERRATA. PMID- 26355147 TI - Plastid RNA polymerases: orchestration of enzymes with different evolutionary origins controls chloroplast biogenesis during the plant life cycle. AB - Chloroplasts are the sunlight-collecting organelles of photosynthetic eukaryotes that energetically drive the biosphere of our planet. They are the base for all major food webs by providing essential photosynthates to all heterotrophic organisms including humans. Recent research has focused largely on an understanding of the function of these organelles, but knowledge about the biogenesis of chloroplasts is rather limited. It is known that chloroplasts develop from undifferentiated precursor plastids, the proplastids, in meristematic cells. This review focuses on the activation and action of plastid RNA polymerases, which play a key role in the development of new chloroplasts from proplastids. Evolutionarily, plastids emerged from the endosymbiosis of a cyanobacterium-like ancestor into a heterotrophic eukaryote. As an evolutionary remnant of this process, they possess their own genome, which is expressed by two types of plastid RNA polymerase, phage-type and prokaryotic-type RNA polymerase. The protein subunits of these polymerases are encoded in both the nuclear and plastid genomes. Their activation and action therefore require a highly sophisticated regulation that controls and coordinates the expression of the components encoded in the plastid and nucleus. Stoichiometric expression and correct assembly of RNA polymerase complexes is achieved by a combination of developmental and environmentally induced programmes. This review highlights the current knowledge about the functional coordination between the different types of plastid RNA polymerases and provides working models of their sequential expression and function for future investigations. PMID- 26355148 TI - Solid-state NMR investigations of cellulose structure and interactions with matrix polysaccharides in plant primary cell walls. AB - Until recently, the 3D architecture of plant cell walls was poorly understood due to the lack of high-resolution techniques for characterizing the molecular structure, dynamics, and intermolecular interactions of the wall polysaccharides in these insoluble biomolecular mixtures. We introduced multidimensional solid state NMR (SSNMR) spectroscopy, coupled with (13)C labelling of whole plants, to determine the spatial arrangements of macromolecules in near-native plant cell walls. Here we review key evidence from 2D and 3D correlation NMR spectra that show relatively few cellulose-hemicellulose cross peaks but many cellulose-pectin cross peaks, indicating that cellulose microfibrils are not extensively coated by hemicellulose and all three major polysaccharides exist in a single network rather than two separate networks as previously proposed. The number of glucan chains in the primary-wall cellulose microfibrils has been under active debate recently. We show detailed analysis of quantitative (13)C SSNMR spectra of cellulose in various wild-type (WT) and mutant Arabidopsis and Brachypodium primary cell walls, which consistently indicate that primary-wall cellulose microfibrils contain at least 24 glucan chains. PMID- 26355149 TI - Enhancing diterpenoid concentration in Salvia miltiorrhiza hairy roots through pathway engineering with maize C1 transcription factor. AB - Tanshinones are valuable natural diterpenoids from danshen (Salvia miltiorrhiza Bunge). Here, it was demonstrated that maize transcription factor C1 improved the accumulation of tanshinones by comprehensively upregulating the pathway genes, especially SmMDC and SmPMK in danshen hairy roots, yielding total tanshinones up to 3.59mg g(-1) of dry weight in line C1-6, a 3.4-fold increase compared with the control. Investigation of 2024bp of the SmMDC promoter fragment revealed that C1 mediated upregulation of terpenoid genes was possibly due to the direct interaction of C1 with its recognition sequences. The increase of tanshinones was accompanied by a decrease of salvianolic acid production, the other bioactive ingredient in danshen, by up to 37% compared with the control. This was the result of the downregulation of SmTAT, the entry-point gene of the tyrosine pathway, which promoted metabolic flow to anthocyanins rather than to salvianolic acids. Based on the findings of the present study, it was concluded that cis acting elements shared by terpenoid and phenylpropanoid biosynthetic genes are partially responsible for the C1-stimulated variation of tanshinone and salvianolic acid concentrations. PMID- 26355150 TI - Effector T Cell Egress via Afferent Lymph Modulates Local Tissue Inflammation. AB - Memory/effector T cells recirculate through extralymphoid tissues by entering from blood and egressing via afferent lymph. Although T cell entry into effector sites is key to inflammation, the relevance of T cell egress to this process is unknown. In this study, we found that Ag recognition at the effector site reduced the tissue egress of proinflammatory Th1 cells in a mouse model of delayed hypersensitivity. Transgenic expression of "tissue exit receptor" CCR7 enhanced lymphatic egress of Ag-sequestered Th1 cells from the inflamed site and alleviated inflammation. In contrast, lack of CCR7 on Th1 cells diminished their tissue egress while enhancing inflammation. Lymph-borne Th1 and Th17 cells draining the inflamed skin of sheep migrated toward the CCR7 ligand CCL21, suggesting the CCR7-CCL21 axis as a physiological target in regulating inflammation. In conclusion, exit receptors can be targeted to modulate T cell dwell time and inflammation at effector sites, revealing T cell tissue egress as a novel control point of inflammation. PMID- 26355151 TI - Multi-Inhibitory Effects of A2A Adenosine Receptor Signaling on Neutrophil Adhesion Under Flow. AB - A2A adenosine receptor (A2AAR) signaling negatively regulates inflammatory responses in many disease models, but the detailed mechanisms remain unclear. We used the selective A2AAR agonist, ATL313, to examine how A2AAR signaling affects human and murine neutrophil adhesion under flow. Treating neutrophils with ATL313 inhibited selectin-induced, beta2 integrin-dependent slow rolling and chemokine induced, beta2 integrin-dependent arrest on ICAM-1. ATL313 inhibited selectin induced beta2 integrin extension, which supports slow rolling, and chemokine induced hybrid domain "swing-out," which supports arrest. Furthermore, ATL313 inhibited integrin outside-in signaling as revealed by reduced neutrophil superoxide production and spreading on immobilized anti-beta2 integrin Ab. ATL313 suppressed selectin-triggered activation of Src family kinases (SFKs) and p38 MAPK, chemokine-triggered activation of Ras-related protein 1, and beta2 integrin triggered activation of SFKs and Vav cytoskeletal regulatory proteins. ATL313 activated protein kinase A and its substrate C-terminal Src kinase, an inhibitor of SFKs. Treating neutrophils with a protein kinase A inhibitor blocked the actions of ATL313. In vivo, ATL313-treated neutrophils rolled faster and arrested much less frequently in postcapillary venules of the murine cremaster muscle after TNF-alpha challenge. Furthermore, ATL313 markedly suppressed neutrophil migration into the peritoneum challenged with thioglycollate. ATL313 did not affect A2AAR-deficient neutrophils, confirming its specificity. Our findings provide new insights into the anti-inflammatory mechanisms of A2AAR signaling and the potential utility of A2AAR agonists in inflammatory diseases. PMID- 26355152 TI - Selective Conditions Are Required for the Induction of Invariant NKT Cell Hyporesponsiveness by Antigenic Stimulation. AB - Activation of invariant (i)NKT cells with the model Ag alpha-galactosylceramide induces rapid production of multiple cytokines, impacting a wide variety of different immune reactions. In contrast, following secondary activation with alpha-galactosylceramide, the behavior of iNKT cells is altered for months, with the production of most cytokines being strongly reduced. The requirements for the induction of this hyporesponsive state, however, remain poorly defined. In this study, we show that Th1-biasing iNKT cell Ags could induce iNKT cell hyporesponsiveness, as long as a minimum antigenic affinity was reached. In contrast, the Th2-biasing Ag OCH did not induce a hyporesponsive state, nor did cytokine-driven iNKT cell activation by LPS or infections. Furthermore, although dendritic cells and B cells have been reported to be essential for iNKT cell stimulation, neither dendritic cells nor B cells were required to induce iNKT cell hyporesponsiveness. Therefore, our data indicate that whereas some bone marrow-derived cells could induce iNKT cell hyporesponsiveness, selective conditions, dependent on the structure and potency of the Ag, were required to induce hyporesponsiveness. PMID- 26355153 TI - Fstl1 Promotes Asthmatic Airway Remodeling by Inducing Oncostatin M. AB - Chronic asthma is associated with airway remodeling and decline in lung function. In this article, we show that follistatin-like 1 (Fstl1), a mediator not previously associated with asthma, is highly expressed by macrophages in the lungs of humans with severe asthma. Chronic allergen-challenged Lys-Cre(tg) /Fstl1(Delta/Delta) mice in whom Fstl1 is inactivated in macrophages/myeloid cells had significantly reduced airway remodeling and reduced levels of oncostatin M (OSM), a cytokine previously not known to be regulated by Fstl1. The importance of the Fstl1 induction of OSM to airway remodeling was demonstrated in murine studies in which administration of Fstl1 induced airway remodeling and increased OSM, whereas administration of an anti-OSM Ab blocked the effect of Fstl1 on inducing airway remodeling, eosinophilic airway inflammation, and airway hyperresponsiveness, all cardinal features of asthma. Overall, these studies demonstrate that the Fstl1/OSM pathway may be a novel pathway to inhibit airway remodeling in severe human asthma. PMID- 26355154 TI - A Reassessment of IgM Memory Subsets in Humans. AB - From paired blood and spleen samples from three adult donors, we performed high throughput VH sequencing of human B cell subsets defined by IgD and CD27 expression: IgD(+)CD27(+) ("marginal zone [MZ]"), IgD(-)CD27(+) ("memory," including IgM ["IgM-only"], IgG and IgA) and IgD(-)CD27(-) cells ("double negative," including IgM, IgG, and IgA). A total of 91,294 unique sequences clustered in 42,670 clones, revealing major clonal expansions in each of these subsets. Among these clones, we further analyzed those shared sequences from different subsets or tissues for VH gene mutation, H-CDR3-length, and VH/JH usage, comparing these different characteristics with all sequences from their subset of origin for which these parameters constitute a distinct signature. The IgM-only repertoire profile differed notably from that of MZ B cells by a higher mutation frequency and lower VH4 and higher JH6 gene usage. Strikingly, IgM sequences from clones shared between the MZ and the memory IgG/IgA compartments showed a mutation and repertoire profile of IgM-only and not of MZ B cells. Similarly, all IgM clonal relationships (among MZ, IgM-only, and double-negative compartments) involved sequences with the characteristics of IgM-only B cells. Finally, clonal relationships between tissues suggested distinct recirculation characteristics between MZ and switched B cells. The "IgM-only" subset (including cells with its repertoire signature but higher IgD or lower CD27 expression levels) thus appear as the only subset showing precursor-product relationships with CD27(+) switched memory B cells, indicating that they represent germinal center-derived IgM memory B cells and that IgM memory and MZ B cells constitute two distinct entities. PMID- 26355155 TI - Reactivation of Neutralized HIV-1 by Dendritic Cells Is Dependent on the Epitope Bound by the Antibody. AB - Ab-neutralized HIV-1 can be captured by dendritic cells (DCs), which subsequently transfer infectious HIV-1 to susceptible CD4(+) T cells. In this study, we examined the capacity of early Abs, as well as recently identified broadly neutralizing Abs (bNAbs) targeting different envelope glycoprotein (Env) epitopes, to block HIV-1 transmission by immature and mature DCs to HIV-1 sensitive cells. Three bNAbs directed against the gp41 membrane proximal region of Env (2F5, 4E10, and 10E8) and three gp120 bNAbs targeting the CD4 binding site (b12, VRC01, and NIH45-46) were examined. In addition, eight glycan-dependent bNAbs targeting the V1V2 apex (PG9, PG16, and PGT145), the V3 loop (2G12, PGT121, and PGT128), and the gp120-gp41 interface of Env (PGT151 and 35O22) were tested. bNAbs that bound specific glycans showed, depending on the immature or mature state of the DC, diverse efficiencies in HIV-1 trans-infection. All bNAbs that bound the CD4 binding site blocked trans-infection, whereas all bNAbs directed against the membrane proximal region lost neutralizing activity after DC-mediated HIV-1 transmission. To understand how preneutralized HIV-1 can be transferred as infectious virus by DCs, we followed the processing of 2F5-treated HIV-1 by DCs with confocal microscopy. Inhibition of DC-internalization pathways could not reverse the dissociation of 2F5 from HIV-1, suggesting that Ab dissociation occurs directly at the plasma membrane. Collectively, these findings imply that the location of the epitope and the neutralization capacity of these Abs determine the efficiency of DC-mediated HIV-1 transfer. PMID- 26355156 TI - EBI3 Downregulation Contributes to Type I Collagen Overexpression in Scleroderma Skin. AB - IL-12 family cytokines are implicated in the pathogenesis of various autoimmune diseases, but their role in the regulation of extracellular matrix expression and its contribution to the phenotype of systemic sclerosis (SSc) remain to be elucidated. Among the IL-12 family members, IL-35 decreases type I collagen expression in cultured dermal fibroblasts. IL-35 consists of p35 and EBI3 subunits, and EBI3 alone could downregulate the protein and mRNA expression of type I or type III collagen in the presence or absence of TGF-beta costimulation. We found that collagen mRNA stability was reduced by EBI3 via the induction of miR-4500. The IL-35 levels in the sera or on the surface of T cells were not altered in SSc patients, while EBI3 expression was decreased in the keratinocytes of the epidermis and regulatory T cells of the dermis in SSc skin compared with normal skin, which may induce collagen synthesis in SSc dermal fibroblasts. We also found that gp130, the EBI3 receptor, was expressed in both normal and SSc fibroblasts. Moreover, we revealed that EBI3 supplementation by injection into the skin improves mice skin fibrosis. Decreased EBI3 in SSc skin may contribute to an increase in collagen accumulation and skin fibrosis. Clarifying the mechanism regulating the extracellular matrix expression by EBI3 in SSc skin may lead to better understanding of this disease and new therapeutic strategies using ointment or microinjection of the subunit. PMID- 26355157 TI - Requirement for Transcription Factor Ets1 in B Cell Tolerance to Self-Antigens. AB - The differentiation and survival of autoreactive B cells is normally limited by a variety of self-tolerance mechanisms, including clonal deletion, anergy, and clonal ignorance. The transcription factor c-ets-1 (encoded by the Ets1 gene) has B cell-intrinsic roles in regulating formation of Ab-secreting cells by controlling the activity of Blimp1 and Pax5 and may be required for B cell tolerance to self-antigen. To test this, we crossed Ets1(-/-) mice to two different transgenic models of B cell self-reactivity, the anti-hen egg lysozyme BCR transgenic strain and the AM14 rheumatoid factor transgenic strain. BCR transgenic Ets1(-/-) mice were subsequently crossed to mice either carrying or lacking relevant autoantigens. We found that B cells lacking c-ets-1 are generally hyperresponsive in terms of Ab secretion and form large numbers of Ab secreting cells even in the absence of cognate Ags. When in the presence of cognate Ag, different responses were noted depending on the physical characteristics of the Ag. We found that clonal deletion of highly autoreactive B cells in the bone marrow was intact in the absence of c-ets-1. However, peripheral B cells lacking c-ets-1 failed to become tolerant in response to stimuli that normally induce B cell anergy or B cell clonal ignorance. Interestingly, high-affinity soluble self-antigen did cause B cells to adopt many of the classical features of anergic B cells, although such cells still secreted Ab. Therefore, maintenance of appropriate c-ets-1 levels is essential to prevent loss of self-tolerance in the B cell compartment. PMID- 26355158 TI - IFN-gamma Prevents Adenosine Receptor (A2bR) Upregulation To Sustain the Macrophage Activation Response. AB - The priming of macrophages with IFN-gamma prior to TLR stimulation results in enhanced and prolonged inflammatory cytokine production. In this study, we demonstrate that, following TLR stimulation, macrophages upregulate the adenosine 2b receptor (A2bR) to enhance their sensitivity to immunosuppressive extracellular adenosine. This upregulation of A2bR leads to the induction of macrophages with an immunoregulatory phenotype and the downregulation of inflammation. IFN-gamma priming of macrophages selectively prevents the induction of the A2bR in macrophages to mitigate sensitivity to adenosine and to prevent this regulatory transition. IFN-gamma-mediated A2bR blockade leads to a prolonged production of TNF-alpha and IL-12 in response to TLR ligation. The pharmacologic inhibition or the genetic deletion of the A2bR results in a hyperinflammatory response to TLR ligation, similar to IFN-gamma treatment of macrophages. Conversely, the overexpression of A2bR on macrophages blunts the IFN-gamma effects and promotes the development of immunoregulatory macrophages. Thus, we propose a novel mechanism whereby IFN-gamma contributes to host defense by desensitizing macrophages to the immunoregulatory effects of adenosine. This mechanism overcomes the transient nature of TLR activation, and prolongs the antimicrobial state of the classically activated macrophage. This study may offer promising new targets to improve the clinical outcome of inflammatory diseases in which macrophage activation is dysregulated. PMID- 26355159 TI - Urologic cancer in Thailand. AB - Cancer is a major health burden among non-communicable diseases, which has had a high impact on the healthcare system in Thailand. Based on GLOBOCAN, the prevalence of urologic cancer is increasing in Thailand. Prostate, bladder and kidney cancers are 6th, 15th and 22nd most common cancers, respectively, in both males and females. Prostate cancer is the fourth most common cancer in male. Cancer in the lower socioeconomic groups is a challenging problem due to greater exposure to the risk factors and more limited access to the healthcare service. The cancers are usually detected in advanced stages of the cancer. The most common histopathological finding of kidney cancer is a renal cell carcinoma. Transitional cell carcinoma is the most common histopathology of bladder. There is a trend of stage migration to earlier stages at first presentation, probably due to public awareness and laboratory screening. Patients with early stage are treated with minimally invasive modalities such as endoscopic, laparoscopic or robot-assisted laparoscopic surgery. Laparoscopic radical prostatectomy and robot assisted laparoscopic radical prostatectomy is the mainstay treatment of localized prostate cancer with the better outcome and less complication. Androgen deprivation therapy is usually for elderly or unfit patients. The strategy for early detection of early cancer is the important role of Thai urologists to manage these three common urologic cancers. PMID- 26355160 TI - Prediction of renal function after nephroureterectomy in patients with upper tract urothelial carcinoma. AB - OBJECTIVE: The estimated glomerular filtration rate is significantly decreased after nephroureterectomy. Deteriorating renal function likely affects the eligibility for cisplatin-based chemotherapy in patients with upper tract urothelial carcinoma. The present study was undertaken to identify preoperative factors for the prediction of postoperative renal function and develop a prediction model. METHODS: Between June 1996 and January 2014, 110 patients who underwent radical nephroureterectomy at our institution were analyzed in this study. The estimated glomerular filtration rate was calculated using the Modification of Diet in Renal Disease study equation. Univariate linear regression analyses were performed to investigate the correlation between postoperative estimated glomerular filtration rate and preoperative variables. A stepwise multivariate linear regression analysis was performed to identify independent predictors of postoperative estimated glomerular filtration rate. RESULTS: Comparison of preoperative and postoperative estimated glomerular filtration rate for each patient showed a median difference of 13.1 ml/min/1.73 m(2). The postoperative estimated glomerular filtration rate was significantly lower than the preoperative estimated glomerular filtration rate (P < 0.001). On univariate analysis, age and preoperative estimated glomerular filtration rate were significantly correlated with postoperative estimated glomerular filtration rate. On multivariate analysis, age, preoperative estimated glomerular filtration rate and the presence of hydronephrosis were independent predictive factors of postoperative estimated glomerular filtration rate. The predicted postoperative estimated glomerular filtration rate, which was calculated using these independent factors, showed a significant correlation with the observed postoperative estimated glomerular filtration rate (correlation coefficient = 0.7533). CONCLUSIONS: Age, preoperative estimated glomerular filtration rate and the presence of hydronephrosis were independent predictors of postoperative estimated glomerular filtration rate in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy. The predicted postoperative estimated glomerular filtration rate based on these factors may be useful for choosing alternative management strategies such as neoadjuvant chemotherapy for patients with upper tract urothelial carcinoma. PMID- 26355161 TI - Unexpected radiation laryngeal necrosis after carbon ion therapy using conventional dose fractionation for laryngeal cancer. AB - Carbon ion therapy is a type of radiotherapy that can deliver high-dose radiation to a tumor while minimizing the dose delivered to organs at risk. Moreover, carbon ions are classified as high linear energy transfer radiation and are expected to be effective for even photon-resistant tumors. A 73-year-old man with glottic squamous cell carcinoma, T3N0M0, refused laryngectomy and received carbon ion therapy of 70 Gy (relative biological effectiveness) in 35 fractions. Three months after the therapy, the patient had an upper airway inflammation, and then laryngeal edema and pain occurred. Five months after the therapy, the airway stenosis was severe and computed tomography showed lack of the left arytenoid cartilage and exacerbation of laryngeal necrosis. Despite the treatment, 5 and a half months after the therapy, the laryngeal edema and necrosis had become even worse and the surrounding mucosa was edematous and pale. Six months after the therapy, pharyngolaryngoesophagectomy and reconstruction with free jejunal autograft were performed. The surgical specimen pathologically showed massive necrosis and no residual tumor. Three years after the carbon ion therapy, he is alive without recurrence. The first reported laryngeal squamous cell carcinoma case treated with carbon ion therapy resulted in an unexpected radiation laryngeal necrosis. Tissue damage caused by carbon ion therapy may be difficult to repair even for radioresistant cartilage; therefore, hollow organs reinforced by cartilage, such as the larynx, may be vulnerable to carbon ion therapy. Caution should be exercised when treating tumors in or adjacent to such organs with carbon ion therapy. PMID- 26355162 TI - Prognostic impact of bulky swollen lymph nodes in cN1 non-small cell lung cancer patients. AB - OBJECTIVE: The aim of this study was to analyze clinicopathological backgrounds and prognosis of clinical N1 non-small cell lung cancer and clarify the difference between bulky and non-bulky cN1 diseases. METHODS: We reviewed 110 patients with completely resected cN1 non-small cell lung cancer and examined the prognostic impact of lymph node size. We classified the swollen lymph nodes into two groups based on their size on chest computed tomography: short-axis diameter >=20 mm (=bulky group) or <20 mm (=non-bulky group). RESULTS: The bulky group consisted of 10 patients, and the non-bulky group comprised 100 patients. There was no significant difference in the upstaging rate to pathological N2 between the bulky and non-bulky groups (31% vs. 30%; P = 0.63). The 5-year recurrence free survival rate and 5-year overall survival rate of both groups did not differ significantly (P = 0.36, P = 0.30, respectively). Our results suggested the possibility that the size of the swollen lymph nodes had no impact on the prognosis in cN1 non-small cell lung cancer patients. In comparison of surgical procedure, pneumonectomy was performed in the bulky group more frequently than the non-bulky group (70% vs. 19%; P < 0.01). CONCLUSIONS: Bulky cN1 disease was not different from non-bulky disease in the prognosis and the upstaging rate to pN2. Curative resection should be indicated to resectable bulky cN1 disease as with non-bulky disease, with careful pre-operative evaluation and preparation considering the possibility of pneumonectomy. PMID- 26355163 TI - Tumor necrosis predicts poor clinical outcomes in patients with node-negative upper urinary tract urothelial carcinoma. AB - OBJECTIVE: Tumor necrosis has been indicated as a factor for the poor clinical outcome in human cancers. We aim to disclose the association between tumor necrosis and overall survival and recurrence-free survival in node-negative upper urinary tract urothelial carcinoma patients treated with radical nephroureterectomy. METHODS: A retrospective cohort of 100 patients with upper urinary tract urothelial carcinoma from January 1990 to June 2011 was enrolled in this study. Univariate analysis with Log-rank test and multivariate analysis with Cox proportional hazards regression models were conducted to determine the correlations of tumor necrosis with overall survival and recurrence-free survival. RESULTS: Tumor necrosis was presented in 48 patients with upper urinary tract urothelial carcinoma and was significantly associated with the advanced pathological stage (P < 0.001), high tumor grade (P < 0.001), subsequent bladder tumor (P = 0.018), vascular invasion (P < 0.001) and lymph node metastasis (P = 0.026). Multivariate analysis revealed tumor necrosis as an independent unfavorable predictor of overall survival in node-negative upper urinary tract urothelial carcinoma patients by multivariate analysis (hazard ratio = 9.23, 95% confidence interval = 1.05-80.89, P = 0.045). CONCLUSIONS: Tumor necrosis was an independent factor of adverse clinical outcomes in node-negative upper urinary tract urothelial carcinoma patients who received radical nephroureterectomy. Evaluation of tumor necrosis might be of clinical significance to determine whether patients with node-negative upper urinary tract urothelial carcinoma should be given further therapy after radical nephroureterectomy. PMID- 26355166 TI - The Editor's point of view: On the study on argon-plasma cleaning of customised abutments. PMID- 26355165 TI - On Argon-plasma cleaning - some comments from regulatory and scientific perspectives. PMID- 26355164 TI - A randomized Phase II trial of systemic chemotherapy with and without trastuzumab followed by surgery in HER2-positive advanced gastric or esophagogastric junction adenocarcinoma with extensive lymph node metastasis: Japan Clinical Oncology Group study JCOG1301 (Trigger Study). AB - Pre-operative chemotherapy with S-1 plus cisplatin is considered to be acceptable as one of the standard treatment options for gastric cancer patients with extensive lymph node metastases in Japan. Addition of trastuzumab to chemotherapy is shown to be effective for HER2-positive advanced gastric cancer patients, and we have commenced a randomized Phase II trial in March 2015 to evaluate S-1 plus cisplatin plus trastuzumab compared with S-1 plus cisplatin alone in the neoadjuvant setting for HER2-positive gastric cancer patients with ELM, which are followed by adjuvant chemotherapy with S-1 for 1 year. A total of 130 patients will be accrued from 41 Japanese institutions over 3 years. The primary endpoint is overall survival. The secondary endpoints are progression-free survival, response rate of pre-operative chemotherapy, proportion of patients with R0 resection, proportion of patients who complete the pre-operative chemotherapy and surgery, proportion of patients who complete the protocol treatment including post-operative chemotherapy, pathological response rate and adverse events. This trial has been registered in the UMIN Clinical Trials Registry as UMIN 000016920. PMID- 26355167 TI - Posterior jaws rehabilitated with partial prostheses supported by 4.0 x 4.0 mm or by longer implants: Four-month post-loading data from a randomised controlled trial. AB - PURPOSE: To evaluate whether 4.0 x 4.0 mm dental implants could be an alternative to implants at least 8.5 mm long, which were placed in posterior jaws in the presence of adequate bone volumes. MATERIALS AND METHODS: One hundred and fifty patients with posterior (premolar and molar areas) mandibles having at least 12.5 mm bone height above the mandibular canal or 11.5 mm bone height below the maxillary sinus, were randomised according to a parallel group design, in order to receive one to three 4.0 mm-long implants or one to three implants which were at least 8.5 mm long, at three centres. All implants had a diameter of 4.0 mm. Implants were loaded after 4 months with definitive screw-retained prostheses. Patients were followed up to 4-month post-loading and outcome measures were prosthesis and implant failures, any complications and peri-implant marginal bone level changes. RESULTS: No patients dropped-out before the 4-month evaluation. Three patients experienced the early failures of one 4.0 mm-long implant each, in comparison to two patients who lost one long implant each (difference in proportion = 0.01; 95% CI -0.06 to 0.09; P = 0.50). Consequently, two prostheses in each group could not be delivered as planned (difference in proportion = 0; 95% CI -0.07 to 0.07; P = 0.69), and one patient from each group is still waiting to have their prostheses delivered. Three short implant patients experienced three complications versus two long implant patients (difference in proportion = 0.01; 95% CI -0.06 to 0.09; P = 0.50). There were no statistically significant differences in prosthesis failures, implant failures and complications. Patients with short implants lost on average 0.38 mm of peri-implant bone at 4 months and patients with long mandibular implants lost 0.42 mm. There were no statistically significant differences in bone level changes up to 4 months between short and long implants (mean difference = 0.04 mm; 95% CI: -0.041 to 0.117; P = 0.274). CONCLUSIONS: Four months after loading, 4.0 x 4.0 mm implants achieved similar results as 8.5 x 4.0 mm-long or longer implants in posterior jaws, however 5 to 10 years post-loading data are necessary before reliable recommendations can be made. PMID- 26355168 TI - The effectiveness of a resorbable bone substitute with a resorbable membrane in the treatment of periodontal infrabony defect - A multicenter randomised controlled trial. AB - PURPOSE: To evaluate the effectiveness of a bone substitute covered with a resorbable membrane versus open flap debridement for the treatment of periodontal infrabony defects. MATERIALS AND METHODS: Ninety-seven patients with one infrabony defect, which was 3 mm or deeper and at least 2 mm wide were randomly allocated either to grafting with a bone substitute covered with a resorbable barrier (BG group) or open flap debridement (OFD group) according to a parallel group design in five European centres. Blinded outcome measures assessed tooth loss, complications, patient's satisfaction with treatment and aesthetics, changes in probing attachment levels (PAL), probing pocket depths (PPD), gingival recessions (REC), radiographic bone levels (RAD) on standardised periapical radiographs, plaque index (PI) and marginal bleeding index (MBI). RESULTS: 49 patients were randomly allocated to the BG group and 48 to the OFD group. At baseline there were more mobile teeth in the BG group (29 versus 15). One year after treatment two patients dropped out from the BG group and no teeth were lost. Three complications (minor postoperative wound dehiscence) occurred in the BG group versus none in the OFD group, where the difference was not statistically significant. The BG group obtained significantly greater statistical PAL gain (mean difference = -0.8 mm, 95% CI [-1.51; -0.03], P = 0.0428), PPD reduction (mean difference = -1.1 mm, 95% CI [-1.84; -0.19], P = 0.0165) and RAD gain (mean difference = -1.2 mm, 95% CI [-2.0; -0.4], P = 0.0058) compared to the OFD group. No statistically significant differences between the groups were observed for gingival recession, or the patient's satisfaction with the treatment and aesthetics. There were some statistically significant differences between the centres for PAL and PPD with the Italian centres reporting better outcomes. CONCLUSIONS: The use of a bone substitute covered with a resorbable membrane yielded significantly better statistical clinical outcomes than open flap debridement in the treatment of periodontal infrabony defects deeper than 3 mm, with regard to PAL gain, PPD reduction and RAD gain. PMID- 26355169 TI - Safety and effectiveness of early loaded maxillary titanium implants with a novel nanostructured calcium-incorporated surface (Xpeed): 3-year results from a pilot multicenter randomised controlled trial. AB - PURPOSE: To evaluate clinical safety and effectiveness of a novel calcium incorporated titanium implant surface (Xpeed, MegaGen Implant Co., Gyeongbuk, South Korea). MATERIALS AND METHODS: Sixty patients were randomised to receive one to six implants in the maxilla with either calcium-incorporated (Xpeed) or control resorbable blasted media (RBM) surfaces, according to a parallel group design at two centres. Implants were submerged and exposed at three different endpoints in equal groups of 20 patients, each at 12, 10 and 8 weeks, respectively. Within 2 weeks, implants were functionally loaded with provisional or definitive prostheses. Outcome measures were prosthesis failures, implant failures, any complications and peri-implant marginal bone level changes. RESULTS: Thirty patients received 45 calcium-incorporated implants and 30 patients received 42 control titanium implants. Three years after loading four patients dropped-out from the Xpeed group and one from the RBM group. No prosthesis or implant failures occurred. There were no statistically significant differences between the groups for complications (P = 0.91; difference in proportions = 0.79 %; 95% CI -0.71 to 2.29) and mean marginal bone level changes (P = 0.88; mean difference = -0.02 mm; 95% CI -0.26 to 0.22). CONCLUSIONS: Both implant surfaces provided good clinical results and no significant difference was found when comparing titanium implants with a nanostructured calcium-incorporated surface versus implants with RBM surfaces. PMID- 26355170 TI - Short implants versus bone augmentation for placing longer implants in atrophic maxillae: One-year post-loading results of a pilot randomised controlled trial. AB - PURPOSE: To evaluate whether short (5.0 to 8.5 mm) dental implants could be a suitable alternative to longer (at least 11.5 mm-long) implants placed in atrophic maxillae augmented with autogenous bone for supporting dental prostheses. MATERIALS AND METHODS: Twenty-eight patients with fully edentulous atrophic maxillae, whom had 5 to 9 mm of residual crestal bone height which was at least 5 mm thick, measured using computerised tomography (CT) scans, were randomised into two groups either to receive 4 to 8 short (5.0 to 8.5 mm) implants (15 patients) or autogenous bone from the iliac crest to allow the placement of at least 11.5 mm-long implants (13 patients). Bone blocks and the windows at the maxillary sinuses were covered with rigid resorbable barriers. Grafts were left to heal for 4 months before placing implants which were submerged. After 4 months, provisional reinforced acrylic prostheses or bar retained overdentures were delivered. Provisional prostheses were replaced, after 4 months, by definitive screw-retained metal-resin cross-arch restorations. Outcome measures were prosthesis and implant failures, any complications, peri implant marginal bone level changes and patient satisfaction. Patients were followed up to 1 year after loading. RESULTS: All patients were rehabilitated with implant-supported prostheses but two patients dropped out from the augmented group. One bilateral sinus lift procedure failed for infection, although short implants could be placed. One implant failed in the augmented group versus two short implants in two patients (Fishers exact test P = 1.00; difference in proportions = 0.06; 95% CI -0.28 to 0.17). All failures occurred before loading. Significantly more complications occurred in augmented patients: eight complications occurred in 5 augmented patients (all of them complained of pain 1 month after bone harvesting from the iliac crest) versus no complications in the short implant (Fisher's exact test P = 0.013; difference in proportions = 0.38; 95% CI 0.11 to 0.65). Both groups presented a significant peri-implant marginal bone loss at 1 year after loading (P < 0.0001); -1.05 (0.20) mm for short implants and -1.01 (0.16) mm for the augmented group, respectively, with no statistically significant differences between the two groups (mean difference 0.04 mm; 95% CI -0.22 to 0.14; P = 0.59). All patients were fully satisfied with the treatment and would have it again. CONCLUSIONS: This pilot study suggests that short implants may be a suitable, cheaper and faster alternative to longer implants placed in bone augmented with autogenous bone for rehabilitating edentulous atrophic maxillae, however, these preliminary results need to be confirmed by larger trials with follow-ups of at least 5 years. PMID- 26355171 TI - Comparing membranes and bone substitutes in a one-stage procedure for horizontal bone augmentation. A double-blind randomised controlled trial. AB - PURPOSE: The objective of this parallel randomised controlled trial is to compare two bone substitutes and collagen membranes in a one-stage procedure for horizontal bone augmentation: anorganic bovine bone (Bio-Oss) and collagen porcine membranes (Bio-Gide) (BB group) versus a synthetic resorbable bone graft substitute made of pure beta-tricalcium phosphate (Ceros TCP) and porcine pericardium collagen membranes (Jason) (CJ group). MATERIALS AND METHODS: Patients in need of implant treatment having at least one site with horizontal osseous defects at a private clinic in Rimini (Italy) were included in this study. Patients were randomised to receive either the BB or CJ treatment. Randomisation was computer-generated with allocation concealment by opaque sequentially numbered sealed envelopes. Patients and the outcome assessor were blinded to group assignment. The main outcome measures were implant failure, complications, clinical bone gain at augmented sites, and complete filling of the bone defect. Secondary outcome measures were chair-time, postoperative pain and peri-implant marginal bone level changes. RESULTS: Twenty-five patients with 32 implants were allocated to the BB group and 25 patients with 29 implants to the CJ group. All 50 randomised patients received the treatment as allocated and there were no dropouts up to 6-months post-loading (12 months post-surgery). There were no failures and there were three complications in the BB group and three complications in the CJ group (relative risk: 1.00, 95% CI from 0.22 to 4.49, P = 1.00). The estimated difference between treatments in the vertical defect bone gain was -0.15 mm (95% CI from -0.65 to 0.35, P = 0.5504) favouring the BB group, and the estimated difference between treatments in the horizontal defect bone gain was -0.27 mm (95%CI from -0.73 to 0.19, P = 0.3851) favouring the BB group. There was no difference in the complete filling of the defect (relative risk: 0.88, 95%CI from 0.58 to 1.34, P = 0.7688). No significant differences were detected for chair-time (P = 0.3524), for VAS pain immediately after surgery (P = 0.5644), VAS pain after 1 week (P = 0.5074) and VAS pain after 2 weeks (P = 0.6950). A slight difference (0.24 mm, 95%CI from 0.0004 to 0.47, P = 0.0464) was detected in radiographic peri-implant bone loss favouring the CJ group. CONCLUSIONS: No significant differences, except for radiographic bone loss, were observed in this randomised controlled trial comparing anorganic bovine bone with collagen porcine membranes versus synthetic resorbable bone made of pure beta-tricalcium phosphate with pericardium collagen membranes for horizontal augmentation. PMID- 26355172 TI - Implant site preparation using a single bur versus multiple drilling steps: 4 month post-loading results of a multicenter randomised controlled trial. AB - PURPOSE: To compare the clinical outcome of implants inserted in sites prepared with a simplified protocol consisting of one single drill versus multiple conventional drilling steps. MATERIALS AND METHODS: In two private clinics, 40 patients, requiring one single implant and having a residual bone height of at least 10 mm and a thickness of at least 5 mm measured on computerised tomography (CT) scans, were randomised after flap elevation to have the implant site prepared using a single drilling step with a newly designed tapered-cylinder drill (1-drill group) or a conventional procedure with multiple drills (multiple drill group). Implants were left to heal non-submerged for 3 months and then they were loaded with a final metal-ceramic crown. Outcome measures were: implant failure; any complications; peri-implant marginal bone level changes assessed by a blinded outcome assessor; operation time; operator preference and post-surgical pain, swelling and analgesic consumption. All patients were followed up to 4 months after implant loading. RESULTS: Twenty patients were randomised to the 1 drill group and 20 patients to the multiple-drill group. No implant failed and no complications occurred. Four months after loading, implants in the 1-drill group lost 0.54 mm of peri-implant bone versus 0.41 mm for the implants in the multiple drill group. There were no statistically significant differences for marginal bone level changes between the two groups (difference 0.13 mm, 95% CI -0.21; 0.47, P = 0.108). Less time which was statistically significant (3.66 mins, 95% CI 2.69; 4.63, P < 0.0001) was required to place the implant with the single bur. Both operators always preferred the single bur technique. Postoperatively, patients in the 1-drill group vs patients in the multiple-drill group reported statistically significant differences for pain level (difference 27.5, 95% CI 3.3; 51.7, P < 0.0001), number of days in which the swelling persisted (difference 3.4, 95% CI 2.4; 4.4, P < 0.0001) and the number of analgesic drugs taken (difference 2.8, 95% CI 1.4; 4.2, P < 0.0001) CONCLUSIONS: Within the limits of this trial, both drilling techniques produced successful results over a 4-month post-loading follow-up period, but the single bur procedure required less surgical time and lead to less postoperative morbidity. PMID- 26355173 TI - Inferior alveolar nerve laceration after implant site preparation: A case report. AB - PURPOSE: The aim of this article is to present a referred clinical case of an inferior alveolar nerve laceration during the insertion of a dental implant in the mandible, that came to our attention after the injury. MATERIALS AND METHODS: A 71-year-old female was treated by a colleague in order to be rehabilitated with a fixed implant-supported prosthesis for her missing teeth in positions 44, 45 and 46. After implant site osteotomy in region 46, the speed of the surgical motor was not changed; as a consequence, the implant was inserted at 1200 rpm and intruded into the mandibular canal, causing the laceration of the neurovascular bundle. RESULTS: During the first 2 weeks after surgery the patient complained of paresthesia in the mental and lower lip area, with labial ptosis and drooling. After 14 days, the paresthesia reduced and mucosal and gingival normosensitivity was detected; however, the patient complained about hyperesthesia of the lower inside lip. After 21 days, the lower lip tone and function were almost completely restored and the paresthesia was further reduced, however the hyperesthesia persisted. CONCLUSIONS: It is extremely important to pay attention to preventing neurological complications through proper preoperative planning, careful execution of the surgical techniques and correct management of instruments and motor speed settings. The latter procedure should be double-checked by both the operator and the assistant. PMID- 26355174 TI - On the scientific evidence that the sterilization of customized implant abutments is required. PMID- 26355180 TI - Timo J. Partanen (MSc, MPH, PhD) March 13, 1938-May 1, 2015. PMID- 26355181 TI - Mitral valve prolapse and left ventricular systolic function. PMID- 26355182 TI - Biphenotypic extramedullary blast crisis of chronic myeloid leukemia with variant Philadelphia chromosome translocation. PMID- 26355190 TI - Cross-sectional and longitudinal comparisons of metabolic profiles between vegetarian and non-vegetarian subjects: a matched cohort study. AB - Several previous cross-sectional studies have shown that vegetarians have a better metabolic profile than non-vegetarians, suggesting that a vegetarian dietary pattern may help prevent chronic degenerative diseases. However, longitudinal studies on the impact of vegetarian diets on metabolic traits are scarce. We studied how several sub-types of vegetarian diets affect metabolic traits, including waist circumference, BMI, systolic blood pressure (SBP), diastolic blood pressure, fasting blood glucose, total cholesterol (TC), HDL, LDL, TAG and TC:HDL ratio, through both cross-sectional and longitudinal study designs. The study used the MJ Health Screening database, with data collected from 1994 to 2008 in Taiwan, which included 4415 lacto-ovo-vegetarians, 1855 lacto-vegetarians and 1913 vegans; each vegetarian was matched with five non vegetarians based on age, sex and study site. In the longitudinal follow-up, each additional year of vegan diet lowered the risk of obesity by 7 % (95 % CI 0.88, 0.99), whereas each additional year of lacto-vegetarian diet lowered the risk of elevated SBP by 8 % (95 % CI 0.85, 0.99) and elevated glucose by 7 % (95 % CI 0.87, 0.99), and each additional year of ovo-lacto-vegetarian diet increased abnormal HDL by 7 % (95 % CI 1.03, 1.12), compared with non-vegetarians. In the cross-sectional comparisons, all sub-types of vegetarians had lower likelihoods of abnormalities compared with non-vegetarians on all metabolic traits (P<0.001 for all comparisons), except for HDL and TAG. The better metabolic profile in vegetarians is partially attributable to lower BMI. With proper management of TAG and HDL, along with caution about the intake of refined carbohydrates and fructose, a plant-based diet may benefit all aspects of the metabolic profile. PMID- 26355191 TI - Encephalitozoon cuniculi causes focal anterior cataract and uveitis in dogs. AB - Three mongrel dogs, aged 10 months (case 1), 14 months (case 2) and 7.5 years (case 3), were presented because of ophthalmologic disorders of 4 months, 6 months and 7 years duration, respectively. All three dogs were offspring of stray dogs from Hungary and Serbia and had positive serum antibody titres against Encephalitozoon (E.) cuniculi. The two young dogs showed unilateral, the older dog bilateral chronic anterior uveitis with posterior synechia and focal anterior cortical cataract. The fundi that could be evaluated developed focal tapetal hyporeflective lesions in the course of the disease. Dogs 1 and 2 underwent removal of the lens via phacoemulsification. PCR of the lens material was positive for E. cuniculi strains IV and II, respectively. In dog 2 findings suggestive of microsporidia were detected underneath the anterior lens capsule by immunohistochemical staining. In all cases medical treatment consisted of systemic fenbendazole, prednisolone, and topical anti-inflammatory drugs, and additional brinzolamid/timolol for dog 3. For the time being all cases (follow up 23 months, 6 months and 3 months, respectively) are still on topical anti inflammatory therapy. It is concluded that E. cuniculi infections can cause cataract and chorioretinal lesions in dogs. PMID- 26355192 TI - Performance and carcass characteristics of young cattle fed with soybean meal treated with tannins. AB - This study aimed to evaluate the effects of replacement of soybean meal (SBM) with soybean meal treated with tannin (SBMT) on the intake, digestibility, performance and characteristics of the carcasses of young cattle fed a high concentrate diet. Forty-two Nellore bulls with body weight of 244.5 +/- 4.99 kg were used. Diets had the inclusion of 7.5% SBM, with a proportion of that SBM (0, 33, 66 or 100%) replaced for SBMT; and other treatment (SBMT + urea) just with 2.5% of SBM which was treated with tannins. Seven animals were randomly selected and slaughtered, and the remaining animals were distributed on treatments and remained for 112 days. After, all animals were slaughtered. There was a linear decline in dry matter intake (P = 0.026) when SBM was replaced with SBMT. No decrease in carcass weight (P > 0.05) was observed. The efficiency of carcass weight gain showed a quadratic function effect (P = 0.049). There were changes in carcass gain composition when SBMT was added (P < 0.05), with an increase in muscle and reduction in fat deposition. The use of SBMT in place of SBM causes changes in body gain composition in animals and reduces DM intake by the animals, achieving a better feed conversion efficiency. PMID- 26355193 TI - Emotional experience in music fosters 18-month-olds' emotion-action understanding: a training study. AB - We examine whether emotional experiences induced via music-making promote infants' use of emotional cues to predict others' action. Fifteen-month-olds were randomly assigned to participate in interactive emotion training either with or without musical engagement for three months. Both groups were then re-tested with two violation-of-expectation paradigms respectively assessing their sensitivity to some expressive features in music and understanding of the link between emotion and behaviour in simple action sequences. The infants who had participated in music, but not those who had not, were surprised by music-face inconsistent displays and were able to interpret an agent's action as guided by her expressed emotion. The findings suggest a privileged role of musical experience in prompting infants to form emotional representations, which support their understanding of the association between affective states and action. PMID- 26355194 TI - The emerging global epidemic of paediatric inflammatory bowel disease--causes and consequences. AB - Two decades ago, paediatric inflammatory bowel disease (IBD) drew only modest interest from the international paediatric community. Since then, dramatically globally increasing incidence rates have made childhood-onset IBD a priority for most paediatric gastroenterologists. The emerging pandemia of paediatric IBD has fuelled a quest to identify the recent changes in early life exposures that could explain the increasing risk for IBD amongst today's children. Treatment of children with IBD should aim for symptom control but should also target restoration of growth and prevention of pubertal delay. The paediatric IBD phenotype seems to be characterized by more extensive disease location, and some comparative studies have suggested that childhood-onset IBD also represents a more severe phenotype than the adult-onset IBD form. In this review, we analyse recent global incidence trends of paediatric IBD. We present an update on the known and suggested risk factors that could explain the emerging global epidemia of paediatric IBD. We also draw attention to differences in treatment between children and adults with IBD. Finally, we highlight latest follow-up studies that question the proposed dynamic and aggressive nature of childhood-onset IBD. PMID- 26355195 TI - Parents' experiences of being in the Solihull Approach parenting group, 'Understanding Your Child's Behaviour': an interpretative phenomenological analysis. AB - BACKGROUND: Empirical evidence suggests that the Solihull Approach parenting group, 'Understanding Your Child's Behaviour' (UYCB), can improve child behaviour and parental well-being. However, little is known about parents' in-depth experience of participating in the UYCB programme. This study provides an in depth qualitative evaluation of UYCB, focussing on possible moderating factors and mechanisms of change that may inform programme development. METHOD: Ten parents (eight mothers and two fathers), recruited from seven UYCB groups across two locations, were interviewed within 7 weeks of completing the group and again 10 months later. Data were analysed using interpretative phenomenological analysis. RESULTS: Four themes were identified: 'Two Tiers of Satisfaction', 'Development as a Parent', 'Improved Self-belief' and 'The "Matthew Effect"'. In summary, the majority of parents were immensely satisfied at both completion and follow-up: they valued an experience of containment and social support and perceived improvement in specific child difficulties, their experience of parenting, their confidence and their coping. Most parents appeared to have developed more reflective and empathic parenting styles, with self-reported improved behaviour management. Theoretical material was well received, although some struggled with technical language. Positive outcomes appeared to be maintained, even reinforced, at follow-up, and were associated with having few initial child difficulties, perceiving improvement at completion and persevering with the recommendations. Two participants, whose children had the most severe difficulties, perceived deterioration and felt that the group was insufficient for their level of difficulties. CONCLUSION: Through in-depth analysis of parental experiences, UYCB appears to achieve its aims and communicate well its theoretical principles, although change may also occur through processes common to other group programmes (e.g. social support). Recommendations, stemming from the experiences of these parents, include simplified language, separate groups for parents with complex needs, greater emphasis on the importance of perseverance, and additional support for parents who appear to be struggling to make changes. PMID- 26355196 TI - Disparate ultrafast dynamics of itinerant and localized magnetic moments in gadolinium metal. AB - The Heisenberg-Dirac intra-atomic exchange coupling is responsible for the formation of the atomic spin moment and thus the strongest interaction in magnetism. Therefore, it is generally assumed that intra-atomic exchange leads to a quasi-instantaneous aligning process in the magnetic moment dynamics of spins in separate, on-site atomic orbitals. Following ultrashort optical excitation of gadolinium metal, we concurrently record in photoemission the 4f magnetic linear dichroism and 5d exchange splitting. Their dynamics differ by one order of magnitude, with decay constants of 14 versus 0.8 ps, respectively. Spin dynamics simulations based on an orbital-resolved Heisenberg Hamiltonian combined with first-principles calculations explain the particular dynamics of 5d and 4f spin moments well, and corroborate that the 5d exchange splitting traces closely the 5d spin-moment dynamics. Thus gadolinium shows disparate dynamics of the localized 4f and the itinerant 5d spin moments, demonstrating a breakdown of their intra-atomic exchange alignment on a picosecond timescale. PMID- 26355197 TI - John Curry: A Legacy of Innovation. PMID- 26355198 TI - A World Without the ACR. PMID- 26355199 TI - Faster Reporting Speed and Interpretation Errors: Conjecture, Evidence, and Malpractice Implications. PMID- 26355200 TI - Authors' Reply. PMID- 26355202 TI - ICD-10: An Opportunity for Radiology. PMID- 26355201 TI - The Impact of Nonphysician Providers on Diagnostic and Interventional Radiology Practices: Operational and Educational Implications. AB - The numbers of nurse practitioners (NPs) and physician assistants (PAs) are increasing throughout the entire health care enterprise, and a similar expansion continues within radiology. The use of radiologist assistants is growing in some radiology practices as well. The increased volume of services rendered by this growing nonphysician provider subset of the health care workforce within and outside radiology departments warrants closer review, particularly with regard to their potential influence on radiology education and medical imaging resource utilization. In this article (the second in a two-part series), the authors review recent literature and offer recommendations for radiology practices regarding the impact NPs, PAs, and radiologist assistants may have on interventional and diagnostic radiology practices. Their potential impact on medical education is also discussed. Finally, staffing for radiology departments, as a result of an enlarging nonradiology NP and PA workforce ordering diagnostic imaging, is considered. PMID- 26355203 TI - Practical Considerations for Integrating Digital Breast Tomosynthesis Into Clinical Practice. PMID- 26355204 TI - Meaningful Data or Just Measurements? Differences Between Ionization Chamber and Solid-State Detectors. PMID- 26355205 TI - Radiology and Global Health: Interprofessional Collaboration in Educational Initiatives. PMID- 26355206 TI - Meeting in the Middle. PMID- 26355207 TI - The Limits of Economics. PMID- 26355208 TI - Transitioning From Leadership in Training to Leadership in Practice: Advice for Graduating Members-in-Training. PMID- 26355209 TI - Inside Job: Viruses Transfer cGAMP between Cells. AB - The DNA sensor, cyclic GMP-AMP synthase (cGAS), is essential for the detection of viral infection. In a recent issue of Science, two studies, Bridgeman et al. (2015) and Gentili et al. (2015), report a novel mechanism for propagating an antiviral signal between cells, based on the transfer of the cGAS enzymatic product, cyclic GMP-AMP (cGAMP), in viral particles. PMID- 26355210 TI - Exploiting Combinatorial Interactions to Expand NLR Specificity. AB - Intracellular nucleotide-binding leucine-rich repeat (NLR) receptors play central roles in human and plant innate immunity. In this issue of Cell Host & Microbe, Wang et al. (2015) show that a single plant NLR can detect diverse pathogen effectors by partnering with different scaffolding proteins, which can each recognize distinct effector targets. PMID- 26355211 TI - Bacteria in the CF Lung: Isolation Drives Diversity. AB - In-host pathogen evolution influences disease progression and chronicity, but forces that shape this remain poorly understood. In this issue of Cell Host & Microbe, Jorth et al. (2015) describe regional subpopulations of Pseudomonas aeruginosa in lungs from cyctic fibrosis patients and provide support for compartmentalization-driven evolution of this bacterium. PMID- 26355212 TI - Blowing Off Steam: Virus Inhibition of cGAS DNA Sensing. AB - Detection of viral DNA is essential for eliciting mammalian innate immunity. However, viruses have acquired effective mechanisms for blocking host defense. Indeed, in this issue of Cell Host & Microbe, Wu et al. (2015) discover a herpesviral strategy for inhibiting the prominent host sensor of viral DNA, cGAS. PMID- 26355213 TI - S. aureus Toxins Join the DARC Side. AB - Staphylococcus aureus, like other bacterial pathogens, scavenges host iron for growth through incompletely understood mechanisms. In this issue of Cell Host & Microbe, Spaan et al. (2015) demonstrate that two Staphylococcus aureus leukotoxins, HlgAB and LukED, target the Duffy antigen receptor for chemokines on erythrocytes, resulting in lysis and iron release. PMID- 26355215 TI - The Decoy Substrate of a Pathogen Effector and a Pseudokinase Specify Pathogen Induced Modified-Self Recognition and Immunity in Plants. AB - In plants, host response to pathogenic microbes is driven both by microbial perception and detection of modified-self. The Xanthomonas campestris effector protein AvrAC/XopAC uridylylates the Arabidopsis BIK1 kinase to dampen basal resistance and thereby promotes bacterial virulence. Here we show that PBL2, a paralog of BIK1, is similarly uridylylated by AvrAC. However, in contrast to BIK1, PBL2 uridylylation is specifically required for host recognition of AvrAC to trigger immunity, but not AvrAC virulence. PBL2 thus acts as a decoy and enables AvrAC detection. AvrAC recognition also requires the RKS1 pseudokinase of the ZRK family and the NOD-like receptor ZAR1, which is known to recognize the Pseudomonas syringae effector HopZ1a. ZAR1 forms a stable complex with RKS1, which specifically recruits PBL2 when the latter is uridylylated by AvrAC, triggering ZAR1-mediated immunity. The results illustrate how decoy substrates and pseudokinases can specify and expand the capacity of the plant immune system. PMID- 26355214 TI - Frenemies: Signaling and Nutritional Integration in Pathogen-Microbiota-Host Interactions. AB - The mammalian gastrointestinal (GI) microbiota is highly adapted to thrive in the GI environment and performs key functions related to host nutrition, physiology, development, immunity, and behavior. Successful host-bacterial associations require chemical signaling and optimal nutrient utilization and exchange. However, this important balance can be severely disrupted by environmental stimuli, with one of the most common insults upon the microbiota being infectious diseases. Although the microbiota acts as a barrier toward enteric pathogens, many enteric pathogens exploit signals and nutrients derived from both the microbiota and host to regulate their virulence programs. Here we review several signaling and nutrient recognition systems employed by GI pathogens to regulate growth and virulence. We discuss how shifts in the microbiota composition change host susceptibility to infection and how dietary changes or manipulation of the microbiota could potentially prevent and/or ameliorate GI infections. PMID- 26355216 TI - Prediction of Early Childhood Caries via Spatial-Temporal Variations of Oral Microbiota. AB - Microbiota-based prediction of chronic infections is promising yet not well established. Early childhood caries (ECC) is the most common infection in children. Here we simultaneously tracked microbiota development at plaque and saliva in 50 4-year-old preschoolers for 2 years; children either stayed healthy, transitioned into cariogenesis, or experienced caries exacerbation. Caries onset delayed microbiota development, which is otherwise correlated with aging in healthy children. Both plaque and saliva microbiota are more correlated with changes in ECC severity (dmfs) during onset than progression. By distinguishing between aging- and disease-associated taxa and exploiting the distinct microbiota dynamics between onset and progression, we developed a model, Microbial Indicators of Caries, to diagnose ECC from healthy samples with 70% accuracy and predict, with 81% accuracy, future ECC onsets for samples clinically perceived as healthy. Thus, caries onset in apparently healthy teeth can be predicted using microbiota, when appropriately de-trended for age. PMID- 26355217 TI - BIRC2/cIAP1 Is a Negative Regulator of HIV-1 Transcription and Can Be Targeted by Smac Mimetics to Promote Reversal of Viral Latency. AB - Combination antiretroviral therapy (ART) is able to suppress HIV-1 replication to undetectable levels. However, the persistence of latent viral reservoirs allows for a rebound of viral load upon cessation of therapy. Thus, therapeutic strategies to eradicate the viral latent reservoir are critically needed. Employing a targeted RNAi screen, we identified the ubiquitin ligase BIRC2 (cIAP1), a repressor of the noncanonical NF-kappaB pathway, as a potent negative regulator of LTR-dependent HIV-1 transcription. Depletion of BIRC2 through treatment with small molecule antagonists known as Smac mimetics enhanced HIV-1 transcription, leading to a reversal of latency in a JLat latency model system. Critically, treatment of resting CD4+ T cells isolated from ART-suppressed patients with the histone deacetylase inhibitor (HDACi) panobinostat together with Smac mimetics resulted in synergistic activation of the latent reservoir. These data implicate Smac mimetics as useful agents for shock-and-kill strategies to eliminate the latent HIV reservoir. PMID- 26355219 TI - Profiling the Essential Nature of Lipid Metabolism in Asexual Blood and Gametocyte Stages of Plasmodium falciparum. AB - During its life cycle, Plasmodium falciparum undergoes rapid proliferation fueled by de novo synthesis and acquisition of host cell lipids. Consistent with this essential role, Plasmodium lipid synthesis enzymes are emerging as potential drug targets. To explore their broader potential for therapeutic interventions, we assayed the global lipid landscape during P. falciparum sexual and asexual blood stage (ABS) development. Using liquid chromatography-mass spectrometry, we analyzed 304 lipids constituting 24 classes in ABS parasites, infected red blood cell (RBC)-derived microvesicles, gametocytes, and uninfected RBCs. Ten lipid classes were previously uncharacterized in P. falciparum, and 70%-75% of the lipid classes exhibited changes in abundance during ABS and gametocyte development. Utilizing compounds that target lipid metabolism, we affirmed the essentiality of major classes, including triacylglycerols. These studies highlight the interplay between host and parasite lipid metabolism and provide a comprehensive analysis of P. falciparum lipids with candidate pathways for drug discovery efforts. PMID- 26355218 TI - Strain-Specific V3 and CD4 Binding Site Autologous HIV-1 Neutralizing Antibodies Select Neutralization-Resistant Viruses. AB - The third variable (V3) loop and the CD4 binding site (CD4bs) of the HIV-1 envelope are frequently targeted by neutralizing antibodies (nAbs) in infected individuals. In chronic infection, HIV-1 escape mutants repopulate the plasma, and V3 and CD4bs nAbs emerge that can neutralize heterologous tier 1 easy-to neutralize but not tier 2 difficult-to-neutralize HIV-1 isolates. However, neutralization sensitivity of autologous plasma viruses to this type of nAb response has not been studied. We describe the development and evolution in vivo of antibodies distinguished by their target specificity for V3 and CD4bs epitopes on autologous tier 2 viruses but not on heterologous tier 2 viruses. A surprisingly high fraction of autologous circulating viruses was sensitive to these antibodies. These findings demonstrate a role for V3 and CD4bs antibodies in constraining the native envelope trimer in vivo to a neutralization-resistant phenotype, explaining why HIV-1 transmission generally occurs by tier 2 neutralization-resistant viruses. PMID- 26355221 TI - Substrates of the human oligopeptide transporter hPEPT2. AB - Oligopeptide transporters serve important functions in nutrition and pharmacology. In particular, these transporters help maintain the homeostasis of peptides. The peptide-transporter PEPT2 is a high-affinity and low-capacity type oligopeptide transporter from the proton-coupled oligopeptide transporter family. PEPT2 has recently received attention because of its potential application in targeted drug delivery. PEPT2 is widely distributed in kidney, central nervous system, and lung of organisms. In general, all dipeptides, tripeptides, and peptide-like drugs such as beta-lactam antibiotics and angiotensin-converting enzyme inhibitors could be mediated and transported as a substrate of PEPT2. The design of many extant drugs and prodrugs is based on the substrate structure of PEPT2 to accelerate absorption via peptide transporters. Thus, this paper summarizes the substrate features of PEPT2 to promote the rational design of drugs and prodrugs that target peptide transporters. PMID- 26355220 TI - Current Knowledge on Hepatitis E. AB - Although only a single serotype of hepatitis E virus (HEV), the causative agent of hepatitis E, has been identified, there is great genetic variation among the different HEV isolates reported. There are at least four major recognized genotypes of HEV: genotypes 1 and 2 are mainly restricted to humans and linked to epidemic outbreaks in nonindustrialized countries, whereas genotypes 3 and 4 are zoonotic in both developing and industrialized countries. Besides human strains, genotype 3 and 4 strains of HEV have been genetically characterized from swine, sika deer, mongooses, sheep, and rabbits. Currently, there are approximately 11,000 human and animal sequences of HEV available at the International Nucleotide Sequence Database Collaboration. HEV is the major cause of waterborne outbreaks of hepatitis in areas of poor sanitation. Additionally, it is responsible for sporadic cases of viral hepatitis in not only endemic but industrialized countries as well. Transmission of HEV occurs predominantly by the fecal-oral route, although parenteral and perinatal routes have been reported. HEV infection develops in most individuals as a self-limiting, acute, icteric hepatitis; with mortality rates around 1%. However, some affected individuals will develop fulminant hepatic failure, a serious condition that is frequently fatal without a liver transplant. This complication is particularly common when the infection occurs in pregnant women, where mortality rates rise dramatically to up to 25%. Among the preventive measures available to avoid HEV infection, two separate subunit vaccines containing recombinant truncated capsid proteins of HEV have been shown to be highly effective in the prevention of disease. One of them, HEV 239, was approved in China, and its commercialization by Innovax began in November 2012 under the name Hecolin((r)). PMID- 26355222 TI - Prevalence of 7 virulence genes of Legionella strains isolated from environmental water sources of public facilities and sequence types diversity of L. pneumopila strains in Macau. AB - In this study, we analyzed 7 virulence genes in 55 Legionella species (including 29 L. pneumophila and 26 non-L. pneumophila strains) which isolated from environmental water sources of the public facilities in Macau by using PCR and real-time PCR. In addition, 29 Legionella pneumophila isolates were subjected to genotyping by sequence-based typing scheme and compared with the data reported. The detection rate of flaA, pilE, asd, mip, mompS, proA and neuA genes in the L. pneumophila were 100.0%, respectively. The neuA gene was not detected in the non L. pneumophila strains, but flaA, pilE, asd, mip, mompS, and proA genes could be amplified with a positive rate of 15.4%, 15.4%, 53.8%, 38.5%, 15.4%, and 38.5%, respectively. The results from real-time PCR were generally consistent with that of PCR. Those L. pneumophila strains were assigned into 10 sequence types (STs) and ST1 (9/29) was the dominant STs. Four new STs were found to be unique in Macau. The analysis of population structure of L. pneumophila strains which isolated from Macau, Guangzhou and Shenzhen indicated that the similar clones were existed and ST1 was the most prevalent STs. However, the distribution of the subtypes isolated from Macau was not the same extensive as those from Guangzhou and Shenzhen. The different detection rates of the 7 virulence genes in different species of Legionella might reflect their own potential for environmental adaptability and pathogenesis. And the data analyzed from STs diversity indicated the Macau L. pneumophila possessed obvious regional specificity and high genetic diversity. PMID- 26355223 TI - High copy numbers and N terminal insertion position of influenza A M2E fused with hepatitis B core antigen enhanced immunogenicity. AB - The extra domain of influenza M2 protein (M2e) is almost completely conserved among all influenza A virus subtypes. M2e is a promising candidate target for the development of a broad-spectrum recombinant influenza A vaccine. However, the immunogenicity of M2e needs to be improved. Copy numbers of M2e and its fusion expression with different carrier proteins may affect its immunopotency. In this study, we designed and created different constructs through genetic fusion of M2e (MSLLTEVETPTRSEWECRCSDSSD) (A/California/05/2009 (H1N1)) with the N-terminus (HBcAg1-149aa + Cys) by insertion in the N-terminus Hepatitis B Core (HBc) antigen 1-149aa and Middle 78-81aa of HBcAg1-149aa to construct a recombinant M2e based vaccine candidate. These chimeric sequences were expressed in Escherichia coli. We constructed fusion proteins containing influenza A H1N1 influenza virus (2009), as well as one, two, and three copies of M2e and hepatitis B core antigen1-149aa amino acid-optimized codon inserted N and its intermediate. The recombinant protein was expressed and purified. Western blot analysis was employed to evaluate the expression of the M2e recombinant protein containing different copy numbers of M2e. Mice were immunized for two times with the purified fusion protein HBc/M2e BALB/c. Serum levels of M2e antibody gradually increased along with increase in immunity. The levels of different fusion protein M2e antibodies increase with increasing M2e copy number. In addition, the protein antibody level in the N terminal fusion protein is higher than that in intermediate fusion. PMID- 26355224 TI - Products of dentin matrix protein-1 degradation by interleukin-1beta-induced matrix metalloproteinase-3 promote proliferation of odontoblastic cells. AB - We have previously reported that interleukin (IL)-1beta induces matrix metalloproteinase (MMP)-3-regulated cell proliferation in mouse embryonic stem cell (ESC)-derived odontoblast-like cells, suggesting that MMP-3 plays a potentially unique physiological role in regeneration by odontoblast-like cells. MMPs are able to process virtually any component of the extracellular matrix, including collagen, laminin and bioactive molecules. Because odontoblasts produce dentin matrix protein-1 (DMP-1), we examined whether the degraded products of DMP 1 by MMP-3 contribute to enhanced proliferation in odontoblast-like cells. IL 1beta increased mRNA and protein levels of odontoblastic marker proteins, including DMP-1, but not osteoblastic marker proteins, such as osteocalcin and osteopontin. The recombinant active form of MMP-3 could degrade DMP-1 protein but not osteocalcin and osteopontin in vitro. The exogenous degraded products of DMP 1 by MMP-3 resulted in increased proliferation of odontoblast-like cells in a dose-dependent manner. Treatment with a polyclonal antibody against DMP-1 suppressed IL-1beta-induced cell proliferation to a basal level, but identical treatment had no effect on the IL-1beta-induced increase in MMP-3 expression and activity. Treatment with siRNA against MMP-3 potently suppressed the IL-1beta induced increase in DMP-1 expression and suppressed cell proliferation (p < 0.05). Similarly, treatment with siRNAs against Wnt5a and Wnt5b suppressed the IL 1beta-induced increase in DMP-1 expression and suppressed cell proliferation (p < 0.05). Rat KN-3 cells, representative of authentic odontoblasts, showed similar responses to the odontoblast-like cells. Taken together, our current study demonstrates the sequential involvement of Wnt5, MMP-3, DMP-1 expression, and DMP 1 degradation products by MMP-3, in effecting IL-1beta-induced proliferation of ESC-derived odontoblast-like cells. PMID- 26355225 TI - Protective effects on vascular endothelial cell in N'-nitro-L-arginine (L-NNA) induced hypertensive rats from the combination of effective components of Uncaria rhynchophylla and Semen Raphani. AB - Endothelial dysfunction is closely associated with hypertension. Protection of vascular endothelial cell is the key to prevention and treatment of hypertension. Uncaria rhynchophylla total alkaloids and Semen Raphani soluble alkaloid, isolated from traditional Chinese medicine Uncaria rbyncbopbylla and Semen Raphani respectively, exhibit properties of anti-hypertension and protection of blood vessels. In the present study, we observed the protective effect of the combined use of Uncaria rhynchophylla total alkaloids and Semen Raphani soluble alkaloid to the vascular endothelial cell in N'-nitro-L-arginine-induced hypertensive rats and investigate the preliminary mechanism. Blood pressure was detected by non-invasive rats tail method to observe the anti-hypertension effect of drugs. Scanning electron microscopy was used to observe the integrity or shedding state of vascular endothelial cell. The amount of circulating endothelial cells and CD54 and CD62P expression on circulating endothelial cells were tested to evaluate the endothelium function. In this study, we found that the Uncaria rhynchophylla total alkaloids and Semen Raphani soluble alkaloid compatibility can effectively lower the blood pressure, improve the structural integrity of vascular endothelium, and significantly reduce the number of circulating endothelial cells. Furthermore, the mean fluorescence intensity of CD54 and CD62P expressed showed decrease after the intervention of Uncaria rhynchophylla total alkaloids and Semen Raphani soluble alkaloid compatibility. In conclusion, the combination of effective components of the Uncaria rhynchophylla total alkaloids and Semen Raphani soluble alkaloid demonstrated good antihypertension effect and vascular endothelium protective effect. The preliminary mechanism of the protective effect may attribute to relieve the overall low-grade inflammation. PMID- 26355226 TI - The Chinese version of monitoring and evaluation system strengthening tool for human immunodeficiency virus (HIV) capacity building: Development and evaluation. AB - Monitoring and evaluation (M&E) for human immunodeficiency virus (HIV) capacity building has become a significant step for HIV prevention and control. The M&E system strengthening tool published by the United Nations Joint Programme on HIV/AIDS (UNAIDS) was intended to be the most authoritative assessment tool internationally. Facing the fact that the M&E system in China did not function at an optimum level, we considered taking the international standards for reference. By linguistic validating and different stages' discussions and revisions, we came up with the Chinese version of the capacity diagnosis tool with at least 12 components and tested its validity and reliability. The tool turned out to have a sufficiently linguistic validation and proved to be a scientific and feasible instrument which was suitable for China's national conditions. PMID- 26355227 TI - Toad skin extract cinobufatini inhibits migration of human breast carcinoma MDA MB-231 cells into a model stromal tissue. AB - Toad skin extract cinobufatini study has been focused on anticancer activity, especially apoptosis-inducing activity by bufosteroids. The present study examined effect of the toad skin extract on cancer cell migration into model stromal tissues. Human breast carcinoma cell line MDA-MB-231 was incubated in the presence or absence of toad skin extract on a surface of reconstituted type I collagen gel as a model stromal tissue allowing the cells to migrate into the gel. Frozen sections were microscopically observed after azan staining. Data showed a decrease of cell number in a microscopic field and shortening of cell migration into the model stromal tissue in a dose dependent manner. This suggests that toad skin extract may possess migration-preventing activity in addition to cell toxicity such as apoptosis-inducing activity. The multifaceted effects including apoptosis-inducing and cancer cell migration-preventing activities would improve usefulness of toad skin extract cinobufatini as an anticancer medicine. PMID- 26355228 TI - Diseases that precede disability among latter-stage elderly individuals in Japan. AB - Understanding causes of disability among elderly individuals is an important public health issue, particularly because of the increasing rate of disabled elderly individuals and the social costs in a rapidly aging society. Accordingly, we aimed to describe the diseases that precede disability and investigate the types of diseases that are related to severe disability among Japanese elderly individuals aged over 75 years. Using claim data from the latter-stage elderly healthcare system and long-term care insurance system, we identified 76,265 elderly individuals over 75 years old who did not qualify as disabled on April 1, 2011. Among them, 3,715 elderly individuals who had been newly qualified as disabled between April 1, 2011 and March 31, 2012 were selected. Disease codes from the medical claim data in the 6 months prior to disability were collected. All descriptions were developed separately for six groups divided by gender and disability level (low, middle, and high). The results of the ordinal logistic analysis including sex and age revealed that men tended to have significantly higher levels of disability (beta = 0.417, p < 0.001) than women. Cerebrovascular disorder (CVD) was the most common disease in almost all age and disability level groups. In low-level disability groups, cancer in men (12.8%) and arthropathy and fracture in women (11.9% and 13.5%, respectively) were as common as cerebrovascular disorder (12.2% and 9.7%, in men and women, respectively). Stroke was the most common disease for all genders and disability levels. The diseases preceding low-level disability differed by gender. This study demonstrated the need to consider arthropathy and fracture as well as CVD in order to prevent disability. PMID- 26355229 TI - Medicaid reimbursement, prenatal care and infant health. AB - This paper evaluates the impact of state-level Medicaid reimbursement rates for obstetric care on prenatal care utilization across demographic groups. It also uses these rates as an instrumental variable to assess the importance of prenatal care on birth weight. The analysis is conducted using a unique dataset of Medicaid reimbursement rates and 2001-2010 Vital Statistics Natality data. Conditional on county fixed effects, the study finds a modest, but statistically significant positive relationship between Medicaid reimbursement rates and the number of prenatal visits obtained by pregnant women. Additionally, higher rates are associated with an increase in the probability of obtaining adequate care, as well as a reduction in the incidence of going without any prenatal care. However, the effect of an additional prenatal visit on birth weight is virtually zero for black disadvantaged mothers, while an additional visit yields a substantial increase in birth weight of over 20 g for white disadvantaged mothers. PMID- 26355230 TI - Marked differences in the number and type of synapses innervating the somata and primary dendrites of midbrain dopaminergic neurons, striatal cholinergic interneurons, and striatal spiny projection neurons in the rat. AB - Elucidating the link between cellular activity and goal-directed behavior requires a fuller understanding of the mechanisms underlying burst firing in midbrain dopaminergic neurons and those that suppress activity during aversive or non-rewarding events. We have characterized the afferent synaptic connections onto these neurons in the rat substantia nigra pars compacta (SNpc) and ventral tegmental area (VTA), and compared these findings with cholinergic interneurons and spiny projection neurons in the striatum. We found that the average absolute number of synapses was three to three and one-half times greater onto the somata of dorsal striatal spiny projection neurons than onto the somata of dopaminergic neurons in the SNpc or dorsal striatal cholinergic interneurons. A similar comparison between populations of dopamine neurons revealed a two times greater number of somatic synapses on VTA dopaminergic neurons than SNpc dopaminergic neurons. The percentage of symmetrical, presumably inhibitory, synaptic inputs on somata was significantly higher on spiny projection neurons and cholinergic interneurons compared with SNpc dopaminergic neurons. Synaptic data on the primary dendrites yielded similar significant differences for the percentage of symmetrical synapses for VTA dopaminergic vs. striatal neurons. No differences in the absolute number or type of somatic synapses were evident for dopaminergic neurons in the SNpc of Wistar vs. Sprague-Dawley rat strains. These data from identified neurons are pivotal for interpreting their electrophysiological responses to afferent activity and for generating realistic computer models of neuronal networks of striatal and midbrain dopaminergic function. PMID- 26355231 TI - Reply: Comment on 'Meta-analysis of BRAF mutation as a predictive biomarker of benefit from anti-EGFR monoclonal-antibody therapy for RAS wild-type metastatic colorectal cancer'. PMID- 26355233 TI - Identification of tumour-reactive lymphatic endothelial cells capable of inducing progression of gastric cancer. AB - BACKGROUND: Tumour cells and stromal cells interact in the tumour microenvironment; moreover, stromal cells can acquire abnormalities that contribute to tumour progression. However, interactions between lymphatic endothelial cells (LECs) and tumour cells are largely unexamined. In this study, we aimed to determine whether tumour-specific LECs inhabit the tumour microenvironment and examine their influence on this microenvironment. METHODS: We isolated normal LECs (NLECs) from a non-metastatic lymph node and tumour associated LECs (TLECs) from cancerous lymph nodes. We examined proliferative and migratory potency, growth factor production, and gene expression of each type of LEC. Moreover, we developed a co-culture system to investigate the interactions between gastric cancer cells and LECs. RESULTS: When compared with NLEC, TLECs had an abnormal shape, high proliferative and migratory abilities, and elevated expression of genes associated with inflammation, cell growth, and cell migration. NLECs co-cultured with gastric cancer cells from the OCUM12 cell line acquired TLEC-like phenotypes. Also, OCUM12 cells co-cultured with TLECs expressed high levels of genes responsible for metastasis. CONCLUSIONS: Our results demonstrated that LECs interacted with tumour cells and obtained abnormal phenotypes that could have important roles in tumour progression. PMID- 26355234 TI - BRAF-mutated metastatic colorectal cancer between past and future. PMID- 26355232 TI - Evaluation of efficacy and safety markers in a phase II study of metastatic colorectal cancer treated with aflibercept in the first-line setting. AB - BACKGROUND: Aflibercept (ziv-aflibercept) is an anti-angiogenic agent recently approved in combination with FOLFIRI for the treatment of metastatic colorectal cancer (mCRC) patients previously treated with oxaliplatin. Despite heterogeneity in response to aflibercept, no biomarkers for efficacy or adverse effects have been identified. Here we present biomarker data from the randomised phase II AFFIRM trial assessing aflibercept in combination with mFOLFOX6 first line in mCRC. METHODS: Ninety-six somatic mutations in key oncogenic drivers of mCRC and 133 common single-nucleotide polymorphisms (SNPs) in vascular endothelial growth factor (VEGF) pathway genes were analysed, and 27 plasma markers measured at baseline, during and after treatment. We assessed correlations of these three classes of biomarkers with progression-free survival (PFS) and adverse events (AEs). RESULTS: Somatic mutations identified in KRAS, BRAF, NRAS, PIK3CA and PIK3R1 did not significantly correlate with PFS (multiple testing-adjusted false discovery rate (FDR) or multiple testing-adjusted FDR>0.3). None of the individual SNPs correlated with PFS (multiple testing-adjusted FDR>0.22), but at the gene level variability in VEGFB significantly correlated with PFS (multiple testing-adjusted FDR=0.0423). Although none of the plasma markers measured at baseline significantly correlated with PFS, high levels of circulating IL8 at baseline together with increased levels of IL8 during treatment were significantly associated with reduced PFS (multiple testing-adjusted FDR=0.0478). No association was found between biomarkers and AEs. CONCLUSIONS: This represents the first biomarker study in mCRC treated with aflibercept. High IL8 plasma levels at baseline and subsequent increases in IL8 were associated with worse PFS, suggesting that IL8 may act as a potentially predictive biomarker of aflibercept treatment outcome. PMID- 26355235 TI - TERT promoter mutations are frequent and show association with MED12 mutations in phyllodes tumors of the breast. AB - BACKGROUND: Phyllodes tumors are rare fibroepithelial neoplasms of the breast, which carry the potential risk of local recurrence and metastasis. Phyllodes tumors share several histological features with fibroadenomas, and no widely accepted markers for distinguishing these lesions have been identified. METHODS: We analyzed molecular abnormalities related to telomere elongation in tumors, including TERT promoter mutations, as well as loss of expression of ATRX and DAXX, in a total of 104 phyllodes tumors and fibroadenomas. RESULTS: Sequencing analyses showed that TERT promoter mutations were frequent in phyllodes tumors (30/46, 65%), but rare in fibroadenomas (4/58, 7%). Among phyllodes tumors, the mutations were more frequent in borderline tumors (13/15, 87%), but were also common in benign (9/18, 50%) and malignant tumors (8/13, 62%). Remarkably, all but one TERT promoter-mutated tumor also contained MED12 mutations, indicating that these mutations are strongly associated (P=8.4 * 10(-6)). Expression of ATRX and DAXX, as evaluated by immunohistochemistry, was retained in all tumors. CONCLUSIONS: Our observations suggest a critical role of TERT promoter mutations, in cooperation with MED12 mutations, in the development of phyllodes tumors. Because TERT promoter mutations are rare among fibroadenomas, their detection may be of potential use in discriminating between phyllodes tumors and fibroadenomas. PMID- 26355236 TI - Non-pharmacological interventions for people with epilepsy and intellectual disabilities. AB - BACKGROUND: Approximately 30% of patients with epilepsy remain refractory to drug treatment and continue to experience seizures whilst taking one or more antiepileptic drugs (AEDs). Several non-pharmacological interventions that may be used in conjunction with or as an alternative to AEDs are available for refractory patients. In view of the fact that seizures in people with intellectual disabilities are often complex and refractory to pharmacological interventions, it is evident that good quality randomised controlled trials (RCTs) are needed to assess the efficacy of alternatives or adjuncts to pharmacological interventions.This is an updated version of the original Cochrane review (Beavis 2007) published in The Cochrane Library (2007, Issue 4). OBJECTIVES: To assess data derived from randomised controlled trials of non pharmacological interventions for people with epilepsy and intellectual disabilities.Non-pharmacological interventions include, but are not limited to, the following.* Surgical procedures.* Specialised diets, for example, the ketogenic diet, or vitamin and folic acid supplementation.* Psychological interventions for patients or for patients and carers/parents, for example, cognitive-behavioural therapy (CBT), electroencephalographic (EEG) biofeedback and educational intervention.* Yoga.* Acupuncture.* Relaxation therapy (e.g. music therapy). SEARCH METHODS: For the latest update of this review, we searched the Cochrane Epilepsy Group Specialised Register (19 August 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) via CRSO (19 August 2014), MEDLINE (Ovid, 1946 to 19 August 2014) and PsycINFO (EBSCOhost, 1887 to 19 August 2014). SELECTION CRITERIA: Randomised controlled trials of non-pharmacological interventions for people with epilepsy and intellectual disabilities. DATA COLLECTION AND ANALYSIS: Two review authors independently applied the inclusion criteria and extracted study data. MAIN RESULTS: One study is included in this review. When two surgical procedures were compared, results indicated that corpus callosotomy with anterior temporal lobectomy was more effective than anterior temporal lobectomy alone in improving quality of life and performance on IQ tests among people with epilepsy and intellectual disabilities. No evidence was found to support superior benefit in seizure control for either intervention. This is the only study of its kind and was rated as having an overall unclear risk of bias. The previous update (December 2010) identified one RCT in progress. The study authors have confirmed that they are aiming to publish by the end of 2015; therefore this study (Bjurulf 2008) has not been included in the current review. AUTHORS' CONCLUSIONS: This review highlights the need for well-designed randomised controlled trials conducted to assess the effects of non pharmacological interventions on seizure and behavioural outcomes in people with intellectual disabilities and epilepsy. PMID- 26355237 TI - Adrenocortical carcinoma with inferior vena cava, left renal vein and right atrium tumor thrombus extension. AB - INTRODUCTION: Adrenocortical carcinoma (ACC) is a rare, but highly aggressive type of tumor with an annual incidence of 1-2 cases per million. The prognosis is poor with a five-year overall survival rate of ~35%. The poor prognosis may be related to the advanced stage at which the majority of ACCs are detected. Complete surgical resection remains the most effective treatment. PRESENTATION OF THE CASE: A 51-year-old female patient with recent onset of dyspepsia, ascites and peripheral edema was referred to our institution. Computed tomography (CT) and Magnetic Resonance Imaging (MRI) displayed a 8cm O right adrenal mass. Moreover a tumor thrombus jutted out into the IVC, left renal vein and right atrium. An echocardiographic evaluation confirmed the presence of the tumor thrombus in the right atrium. The patient underwent adrenalectomy with removal of its intravascular extension with the assistance of cardiopulmonary bypass and hypothermia. DISCUSSION: ACC is a rare malignancy and ACC with tumor thrombus extension is a rare presentation. Patients can present with a variety of sign and symptoms, depending on the extent of the tumor. CT scan of chest and abdomen represents the gold standard in ACC staging while magnetic resonance imaging (MRI) is preferred for tumor thrombus characterization. Complete surgical resection with a negative margin, R0 resection, is the only curative option for localized disease. Kidney sparing surgery should be performed when possible. CONCLUSION: We present a rare case of Adrenocortical carcinoma with tumor thrombus extending into the IVC and right atrium. Complete resection with negative margins represents the best therapeutic chance for these patients. PMID- 26355238 TI - Endothelial Survival After Descemet Membrane Endothelial Keratoplasty: Effect of Surgical Indication and Graft Adherence Status. AB - IMPORTANCE: This study evaluates the longevity of Descemet membrane endothelial keratoplasty (DMEK) grafts in terms of endothelial survival and endothelial failure. OBJECTIVE: To determine endothelial survival and its association with the indication for surgery and/or partial graft detachment in DMEK. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cross-sectional study of data collected from August 8, 2006, until June 17, 2015, at a tertiary referral center. A total of 352 eyes were evaluated up to 8 years after DMEK for Fuchs endothelial corneal dystrophy (FECD; n = 314), bullous keratopathy (BK; n = 31), and failed previous endothelial graft (n = 7), of which 314 eyes had complete graft attachment and 38 eyes had partial graft detachment (one-third of the graft surface area or less). Endothelial cell density was measured with specular microscopy, and Kaplan-Meier survival estimates were based on eyes with endothelial failure. Endothelial survival was followed up to 8 years after DMEK. MAIN OUTCOMES AND MEASURES: Endothelial cell density, endothelial failure, and endothelial survival. RESULTS: Endothelial cell density decreased to a mean (SD) of 952 (366) and 771 (321) cells/mm2 at 7 and 8 years postoperatively, respectively. Higher endothelial cell densities were found in eyes with FECD compared with those with BK (estimated mean difference, 261 cells/mm2; 95% CI, 118-404; P = .003) and in eyes with attached grafts compared with those with partially detached grafts (estimated mean difference, 330 cells/mm2; 95% CI, 208-452; P < .001), until 8 years. In 11 eyes (3.1%) that had concomitant ocular pathology, endothelial failure occurred within 4 years after DMEK. The overall graft survival probability was 0.96 at 5 and 8 years (95% CI, 0.94-0.99). At 8 years, better survival rates were found in eyes with FECD than in those with BK (survival probability, 0.97 [95% CI, 0.95 0.99] vs 0.84 [95% CI, 0.70-0.99], respectively); until the same follow-up, survival probabilities in eyes with attached and partially detached grafts were 0.97 (95% CI, 0.95-0.99) and 0.91 (95% CI, 0.82-0.99), respectively. CONCLUSIONS AND RELEVANCE: Endothelial decay was higher in eyes with a partial graft detachment than in those with attached grafts and lower in eyes with FECD than in those with BK. Endothelial failure only occurred in eyes with concomitant ocular pathology. These results suggest that eyes with DMEK that have undergone surgery for FECD with a completely attached graft may have an excellent prognosis. PMID- 26355239 TI - The Relationship Between Match-Play Characteristics of Elite Rugby League and Indirect Markers of Muscle Damage. AB - PURPOSE: While exercise-induced muscle damage (EIMD) after rugby league match play has been well documented, the specific match actions that contribute to EIMD are unclear. Accordingly, the purpose of this study was to investigate the positional demands of elite rugby league matches and examine their relationship with subsequent EIMD. METHODS: Twenty-eight performances (from 17 participants) were captured using 10-Hz global positioning systems over 4 competitive matches. Upper- and lower-body neuromuscular fatigue, creatine kinase (CK), and perceived muscle soreness were assessed 24 h before and at 12, 36, and 60 h after matches. RESULTS: High-intensity running was moderately higher in backs (6.6 +/- 2.6 m/min) than in forwards (5.1 +/- 1.6 m/min), whereas total collisions were moderately lower (31.1 +/- 13.1 vs 54.1 +/- 37.0). Duration (r = .90, CI: .77 .96) and total (r = .86, CI: .70-.95) and high-intensity distance covered (r = .76, CI: .51-.91) were associated (P < .05) with increased CK concentration postmatch. Total collisions and repeated high-intensity efforts were associated (P < .05) with large decrements in upper-body neuromuscular performance (r = .48, CI: -.74 to .02; r = -.49, CI: -.77 to .05, respectively), muscle soreness (r = -.68, CI: -.87 to -.10, r = -.66, CI: -.89 to .21, respectively), and CK concentration (r = .67, CI: .42-.85; r = .73, CI: .51-.87, respectively). All EIMD markers returned to baseline within 60 h. CONCLUSION: Match duration, high intensity running, and collisions were associated with variations in EIMD markers, suggesting that recovery is dependent on individual match demands. PMID- 26355240 TI - Becoming a beer expert: is simple exposure with feedback sufficient to learn beer categories? AB - Category learning is an important aspect of expertise development which had been little studied in the chemosensory field. The wine literature suggests that through repeated exposure to wines, sensory information is stored by experts as prototypes. The goal of this study was to further explore this issue using beers. We tested the ability of beer consumers to correctly categorize beers from two different categories (top- and bottom-fermented beers) before and after repeated exposure with feedback to beers from these categories. We found that participants learned to identify the category membership of beers to which they have been exposed but were unable to generalize their learning to other beers. A retrospective verbal protocol questionnaire administrated at the end of the experiment indicates that contrary to what was suggested in the wine literature, prototype extraction is probably not the only mechanism implicated in category learning of foods and beverages. Exemplar-similarity and feature-frequency models might provide a better account of the course of learning of the categorization task studied. PMID- 26355241 TI - Prediction of mortality using quantification of renal function in acute heart failure. AB - BACKGROUND: Renal function, as quantified by the estimated glomerular filtration rate (eGFR), is a predictor of death in acute heart failure (AHF). It is unknown whether one of the clinically-available serum creatinine-based formulas to calculate eGFR is superior to the others for predicting mortality. METHODS AND RESULTS: We quantified renal function using five different formulas (Cockroft Gault, MDRD-4, MDRD-6, CKD-EPI in patients<70 years, and BIS-1 in patients>=70 years) in 1104 unselected AHF patients presenting to the emergency department and enrolled in a multicenter study. Two independent cardiologists adjudicated the diagnosis of AHF. The primary endpoint was the accuracy of the five eGFR equations to predict death as quantified by the time-dependent area under the receiver-operating characteristics curve (AUC). The secondary endpoint was the accuracy to predict all-cause readmissions and readmissions due to AHF. In a median follow-up of 374 days (IQR: 221 to 687 days), 445 patients (40.3%) died. eGFR as calculated by all equations was an independent predictor of mortality. The Cockcroft-Gault formula showed the highest prognostic accuracy (AUC 0.70 versus 0.65 for MDRD-4, 0.55 for MDRD-6, and 0.67 for the combined formula CKD EPI/BIS-1, p<0.05). These findings were confirmed in patients with varying degrees of renal function and in three vulnerable subgroups: women, patients with severe left ventricular dysfunction, and the elderly. The prognostic accuracy for readmission was poor for all equations, with an AUC around 0.5. CONCLUSIONS: Calculating eGFR using the Cockcroft-Gault formula assesses the risk of mortality in patients with AHF more accurately than other commonly used formulas. PMID- 26355243 TI - Therapy: Conscious uncoupling. PMID- 26355242 TI - Hiwi Promotes the Proliferation of Colorectal Cancer Cells via Upregulating Global DNA Methylation. AB - Hiwi is well known for its role in stem cell renewal, maintaining the resting stage, and downregulating cell cycle of stem cells via RNA silencing. And Hiwi overexpression has been recognized in several types of cancers. In the present study, we examined the Hiwi expression in colorectal cancer (CRC) specimens in both mRNA and protein levels via real-time quantitative PCR, western blot assay, and immunohistochemical staining. Then we explored the role of Hiwi in the cancer cell proliferation and in the DNA methylation in human CRC Caro-2 and HT-29 cell lines. Results demonstrated that both mRNA and protein levels of Hiwi were significantly higher in 38 CRC tissues than in 38 peritumor tissues. Moreover, the Hiwi overexpression with an adenovirus vector significantly promoted the proliferation of Caro-2 and HT-29 cells, associated with significant increase in the global DNA methylation levels. And the chemical inhibition of DNA methylation significantly restrained such proliferation promotion. In summary, we confirmed that Hiwi was overexpressed in CRC tissues and that the forced Hiwi overexpression promoted the proliferation and global DNA methylation of CRC cell lines. Our results imply for the first time that Hiwi promotes the proliferation of CRC cells via promoting global DNA methylation. PMID- 26355244 TI - Effect of computerized cognitive rehabilitation program on cognitive function and activities of living in stroke patients. AB - [Purpose] The objective of this study was to examine the effect of cognitive rehabilitation using a computer on cognitive function and activities of daily living in stroke patients presenting impairment of cognitive function. [Subjects] Forty-six stroke patients were divided into two groups (a training group and control group) through random assignment. [Methods] The training group received rehabilitation therapy and an additional computerized cognitive rehabilitation program using The RehaCom software 30 minutes/day, 5 times/week for 5 weeks. The control group received only rehabilitation therapy including physical and occupational therapy. A comparative analysis on all subjects was conducted before and after the experiment using a cognitive test and activities of daily living test. [Results] After 5 weeks of therapy, the training group presented statistically significant improvement in cognitive function assessment items of digit span, visual span, visual learning, auditory continuous performance, visual continuous performance, and others compared with the control group but did not present statistically significant improvement in activities of daily living. [Conclusion] It was revealed through this study that computerized cognitive rehabilitation with the RehaCom program results in improvement in cognitive function and can be used as a treatment tool beneficial to stroke patients presenting cognitive impairment. PMID- 26355245 TI - Molecular analysis of ovarian mucinous carcinoma reveals different cell of origins. AB - It is believed that a subset of primary ovarian mucinous tumors is derived from mature teratomas [1-5]. To confirm this, we performed microsatellite genotyping using a variety of short tandem repeat makers and analyzed allelotypes of 8 mucinous tumors (4 mucinous carcinomas, 3 atypical proliferative mucinous tumors and 1 mucinous cystadenoma) associated with a teratoma to determine whether they were clonally related. 7 of the 8 mucinous tumors showed complete or a high degree of homozygosity. Among the 6 pairs of tumors with teratoma tissue available for comparison, 5 of 6 showed a high or complete degree of allelotypes matching, which differed from the somatic allelotypes of the normal control tissue. A discrepancy was detected between carcinoma and teratoma in one pair at several loci, with different X-chromosome inactivation patterns revealed by the HUMARA clonality assay. We also investigated the allelotypes of 16 ovarian mucinous carcinomas without a teratoma in young patients (range 13-30) and in 6 older patients (range 40-67) using the same method. None of these tumors showed pure homozygosity. The number of homozygous loci in this cohort was significantly lower than that in the first. Our results suggest first, that most mucinous tumors associated with a teratoma are derived from the teratoma but occasionally they could be collision tumors and second that the majority of pure mucinous tumors in young women in whom a teratoma is not present are not derived from a teratoma. PMID- 26355246 TI - Assessment of Parasympathetic Activity in Athletes: Comparing Two Different Methods. AB - INTRODUCTION: A variety of methods are used to assess parasympathetic activity in athletes targeting different organs; however, the reliability of or interchangeability between measurement procedures is not clear. OBJECTIVE: The purpose of this study is to identify the repeatability of two parasympathetic activity measurement procedures, the HR variability during a 4-s exercise test (4sET), and the contractile properties of the pupil (pupillometry), and to assess their agreement. The secondary objective of this study is to assess their relationship with the bronchodilating effect of inhaled ipratropium bromide (iIB), blocking parasympathetic signals to the lungs. METHODS: Forty athletic subjects were enrolled in a cross-sectional study. After 15-min resting in semidarkness, subjects underwent pupillometry (PLR-200TM, NeurOptics Inc., CA), followed by 4sET on a cycle ergometer. HR variability was assessed by Polar Electro(r) HR monitor (RS-800CX/G3; Oy, Kempele, Finland). Both protocols were repeated after 5 min. Statistical analysis was performed according to Bland and Altman and by using Pearson's correlation coefficient and intraclass correlation. Lung function measurements by flow volume curves were performed before and 45 min after iIB. RESULTS: The means of differences were 1.21% (limits of agreement, 3.59 to 6.02) for pupil constriction and 0.05 mm (-0.28 to 0.39) for pupil amplitude. The mean of differences for 4sET was 0.005 (-0.31 to 0.32). A very weak intraclass correlation (r = -0.01, P = 0.58) showed no agreement between the methods. No correlation was observed between pupillometry variables or 4sET with the change in lung function after iIB. CONCLUSION: Pupillometry showed better repeatability compared with the 4sET. There is poor agreement between parasympathetic activity levels measured in three different target organs of athletic subjects; the heart, the pupil, and the lung. Thus, methods assessing parasympathetic activity in different target organs cannot be used interchangeably. PMID- 26355247 TI - Reliability of the Determination of the Ventilatory Threshold in Patients with COPD. AB - PURPOSE: The purpose of this study was to determine the interobserver reliability of the assessment of the ventilatory threshold (VT) using two methods in patients with chronic obstructive pulmonary disease (COPD) and in control subjects. METHODS: VT was identified from incremental exercise testing graphs of 115 subjects (23 controls and 23 in each COPD Global initiative for chronic Obstructive Lung Disease class) by two human observers and a computer analysis using the V-slope method and the ventilatory equivalent method (VEM). Agreement between observers in identifying oxygen uptake at VT (VO 2VT) and HR at VT (HR VT) across disease severity groups was evaluated using intraclass correlation (for humans) and Passing-Bablok regression analysis (human vs computer). RESULTS: For human observers, ICC (95% confidence interval) in determining VO 2VT were higher in controls (0.98 (0.97-0.99) both with V-slope and with VEM) than those in COPD patients (0.72 (0.60-0.81) with V-slope and 0.64 (0.50-0.74) with VEM). Passing-Bablok analysis showed that human and computerized determination of VO 2VT was interchangeable in controls but not in patients with COPD. Forced expiratory volume in one second and peak minute ventilation during exercise were the only variables independently associated with greater interobserver differences in VO 2VT. Interobserver differences in HRVT ranged from 2 +/- 1 (controls) to 10 +/- 3 bpm (GOLD 4). CONCLUSIONS: In patients with COPD, the reliability of human estimation of VO 2VT is less than that in controls and not interchangeable with a computerized analysis. This should be taken into account when using VT for exercise prescription, as a tool to monitor responses to an intervention, as a surrogate measure of overall aerobic fitness, or as a prognostic marker in patients with COPD. PMID- 26355248 TI - Introduction: Sleep and Neurologic Disorders in Chronic Kidney Disease. PMID- 26355249 TI - Cognitive Function in Patients With Chronic Kidney Disease: Challenges in Neuropsychological Assessments. AB - Cognitive dysfunction is a common symptom in patients with chronic kidney disease (CKD). In this review, we highlight the clinical relevance of cognitive impairment in patients with CKD. After a summary of the different pathophysiological components of this frequently overlooked clinical condition, we summarize and evaluate the available neurocognitive tests and reflect on their utility in everyday clinical practice. Finally, we identify future areas of research and allude to the fact that inclusion of cognitive function testing in routine clinical care of patients with CKD could be cost effective by reducing nonadherence to medication and improving quality of life, and even survival. PMID- 26355251 TI - Neurologic Complications After Kidney Transplantation. AB - The clinical focus after kidney transplantation often is centered on graft function. However, neurologic complications are a common, significant, and under recognized contributor to patient morbidity and mortality. Neurologic syndromes can arise through exacerbation of pre-existing conditions or can be newly acquired in the setting of increased risk of infection and drug toxicity after transplantation. We present a comprehensive review of neurologic complications after kidney transplantation. PMID- 26355250 TI - Stroke and Chronic Kidney Disease: Epidemiology, Pathogenesis, and Management Across Kidney Disease Stages. AB - Cerebrovascular disease and stroke are very common at all stages of chronic kidney disease (CKD), likely representing both shared risk factors as well as synergy among risk factors. More subtle ischemic brain lesions may be particularly common in the CKD population, with subtle manifestations including cognitive impairment. For individuals with nondialysis CKD, the prevention, approach to, diagnosis, and management of stroke is similar to the general, non CKD population. For individuals with end-stage renal disease, far less is known regarding strategies to prevent stroke. Stroke prophylaxis using warfarin in dialysis patients with atrial fibrillation in particular remains of uncertain benefit. End-stage renal disease patients can be managed aggressively in the setting of acute stroke. Outcomes after stroke at all stages of CKD are poor, and improving these outcomes should be the subject of future clinical trials. PMID- 26355252 TI - Central Sleep Apnea in Kidney Disease. AB - Sleep is an essential function of life and serves a crucial role in the promotion of health and performance. Poor sleep quality and sleep disorders have been a recurrent finding in patients with chronic kidney disease (CKD). Sleep disorders such as obstructive sleep apnea (OSA) can contribute to hypertension, diabetes, cardiovascular disease, and worsen obesity, all of which are implicated in the etiology of CKD, but CKD itself may lead to OSA. Relationships between CKD/end stage renal disease (ESRD) and OSA have been the subject of numerous investigations, but central sleep apnea (CSA) also is highly prevalent in CKD/ESRD but remains poorly understood, underdiagnosed, and undertreated in these patients. Emerging literature has implicated CSA as another contributor to morbidity and mortality in CKD/ESRD, and several studies have suggested that CSA treatment is beneficial in improving these outcomes. Patients with CKD/ESRD co existing with congestive heart failure are particularly prone to CSA, and studies focused on managing CSA in congestive heart failure patients have provided important information concerning how best to manage CSA in kidney disease as well. Adaptive servo-ventilation ultimately may represent the treatment of choice in these patients, although a stepped approach using a variety of therapeutic modalities is recommended. PMID- 26355253 TI - Restless Legs Syndrome in Patients With Chronic Kidney Disease. AB - Symptoms of restless legs syndrome (RLS) are common in patients with chronic kidney disease (CKD) on dialysis; symptoms of RLS are estimated to affect up to 25% of patients on dialysis when the international RLS diagnostic criteria are applied. RLS is a neurologic disorder with a circadian rhythmicity characterized by an overwhelming urge to move the legs during rest, which can be relieved temporarily by movement. RLS has been associated with an increase in sleep disturbance, higher cardiovascular morbidity, decreased quality of life, and an increased risk of death in patients with CKD. Although the exact pathophysiology of RLS is unknown, it is thought to involve an imbalance in iron metabolism and dopamine neurotransmission in the brain. The symptoms of moderate to severe RLS can be treated with several pharmacologic agents; however, data specific to patients on dialysis with RLS are lacking. The purpose of this article is to examine the relationship between, and complications of, RLS and CKD both in dialysis and nondialysis patients, and discuss the treatment options for patients on dialysis with RLS. PMID- 26355254 TI - Insomnia in Patients With Chronic Kidney Disease. AB - Insomnia and poor self-perceived sleep are very common in patients with chronic kidney disease (CKD). Poor sleep is associated with fatigue, sleepiness, impaired daytime functioning, impaired health-related quality of life, and increased morbidity and mortality. Many illness- and treatment-related factors (metabolic changes, inflammation, altered sleep regulatory mechanisms, symptoms and complications of CKD, comorbid conditions, medications, and renal replacement therapies) may disturb sleep and contribute to the high prevalence of insomnia in this patient population. Accordingly, the approach to both diagnosing and treating this condition is quite complex. Although sleep-related problems are very important for patients with CKD, they largely are under-recognized and undertreated. Very few intervention trials provide an evidence base to support treatment decisions in this particular patient population. With this review we hope to increase awareness of insomnia among professionals involved in the management of patients with CKD and to provide guidance in recognizing and treating this important condition. PMID- 26355255 TI - Hypervolemia and Sleep Apnea in Kidney Disease. AB - In end-stage renal disease (ESRD) and heart failure, conditions characterized by fluid overload, both obstructive sleep apnea (OSA) and central sleep apnea (CSA) are highly prevalent. This observation suggests that fluid overload may be a unifying mechanism in the pathogenesis of both OSA and CSA in these conditions. An overnight rostral fluid shift from the legs to the neck and lungs has been shown to contribute to the pathogenesis of OSA and CSA, respectively, in various different patient populations. This article reviews the evidence that supports a role for fluid overload and overnight fluid shift in the pathogenesis of sleep apnea in ESRD. The diagnosis, epidemiology, and clinical features of sleep apnea in patients with ESRD also are considered. PMID- 26355257 TI - Injuries and Traumatic Psychological Exposures Associated with the South Napa Earthquake - California, 2014. AB - On August 24, 2014, at 3:20 a.m., a magnitude 6.0 earthquake struck California, with its epicenter in Napa County (1). The earthquake was the largest to affect the San Francisco Bay area in 25 years and caused significant damage in Napa and Solano counties, including widespread power outages, five residential fires, and damage to roadways, waterlines, and 1,600 buildings (2). Two deaths resulted (2). On August 25, Napa County Public Health asked the California Department of Public Health (CDPH) for assistance in assessing postdisaster health effects, including earthquake-related injuries and effects on mental health. On September 23, Solano County Public Health requested similar assistance. A household-level Community Assessment for Public Health Emergency Response (CASPER) was conducted for these counties in two cities (Napa, 3 weeks after the earthquake, and Vallejo, 6 weeks after the earthquake). Among households reporting injuries, a substantial proportion (48% in Napa and 37% in western Vallejo) reported that the injuries occurred during the cleanup period, suggesting that increased messaging on safety precautions after a disaster might be needed. One fifth of respondents overall (27% in Napa and 9% in western Vallejo) reported one or more traumatic psychological exposures in their households. These findings were used by Napa County Mental Health to guide immediate-term mental health resource allocations and to conduct public training sessions and education campaigns to support persons with mental health risks following the earthquake. In addition, to promote community resilience and future earthquake preparedness, Napa County Public Health subsequently conducted community events on the earthquake anniversary and provided outreach workers with psychological first aid training. PMID- 26355256 TI - Pruritus in Kidney Disease. AB - Pruritus is a common and distressing symptom in patients with chronic kidney disease. The most recent epidemiologic data have suggested that approximately 40% of patients with end-stage renal disease experience moderate to severe pruritus and that uremic pruritus (UP) has a major clinical impact, being associated strongly with poor quality of life, impaired sleep, depression, and increased mortality. The pathogenesis of UP remains largely unclear, although several theories on etiologic or contributing factors have been proposed including increased systemic inflammation; abnormal serum parathyroid hormone, calcium, and phosphorus levels; an imbalance in opiate receptors; and a neuropathic process. UP can present somewhat variably, although it tends to affect large, discontinuous, but symmetric, areas of skin and to be most symptomatic at night. A variety of alternative systemic or dermatologic conditions should be considered, especially in patients with asymmetric pruritus or other atypical features. Treatment initially should focus on aggressive skin hydration, patient education on minimizing scratching, and optimization of the aspects of chronic kidney disease care that are most relevant to pruritus, including dialysis adequacy and serum parathyroid hormone, calcium, and phosphorus management. Data for therapy specifically for UP remain limited, although topical therapies, gabapentin, type B ultraviolet light phototherapy, acupuncture, and opioid receptor modulators all may play a role. PMID- 26355258 TI - An Inflammatory Polymorphisms Risk Scoring System for the Differentiation of Ischemic Stroke Subtypes. AB - Inflammation has been associated with atherothrombotic stroke and recently with cardioembolic stroke. Different genetic risk factors have been specifically associated with the subtypes of ischemic stroke (cardioembolic, atherothrombotic, and lacunar). However, there are no studies that have generated genetic risk scores for the different subtypes of ischemic stroke using polymorphisms associated with inflammation. METHODS: We have analyzed 68 polymorphisms of 30 inflammatory mediator genes in 2,685 subjects: 1,987 stroke cases and 698 controls. We generated a genetic scoring system with the most significant polymorphisms weighted by the odds ratio of every polymorphism and taken into consideration the stroke subtype. RESULTS: Three polymorphisms, rs1205 (CRP gene), rs1800779, and rs2257073 (NOS3 gene), were associated with cardioembolic stroke (p value <0.05). The score generated was only associated with the cardioembolic stroke subtype (p value: 0.001) and was replicated in an independent cohort (p value: 0.017). The subjects with the highest score presented a cardioembolic stroke in 92.2% of the cases (p value: 0.002). CONCLUSION: The genetics of inflammatory markers is more closely associated with cardioembolic strokes than with atherothrombotic or lacunar strokes. The genetic risk scoring system could be useful in the prediction and differentiation of ischemic stroke; however, it might be specific to particular ischemic stroke subtypes. PMID- 26355259 TI - Correction to Synthesis of N-Imidoyl and N-Oxoimidoyl Sulfoximines from 1 Alkynes, N-Sulfonyl Azides, and Sulfoximines. PMID- 26355260 TI - Mechanisms of Alizarin Red S and Methylene blue biosorption onto olive stone by product: Isotherm study in single and binary systems. AB - The biosorption process of anionic dye Alizarin Red S (ARS) and cationic dye methylene blue (MB) as a function of contact time, initial concentration and solution pH onto olive stone (OS) biomass has been investigated. Equilibrium biosorption isotherms in single and binary systems and kinetics in batch mode were also examined. The kinetic data of the two dyes were better described by the pseudo second-order model. At low concentration, ARS dye appeared to follow a two step diffusion process, while MB dye followed a three-step diffusion process. The biosorption experimental data for ARS and MB dyes were well suited to the Redlich Peterson isotherm. The maximum biosorption of ARS dye, qmax = 16.10 mg/g, was obtained at pH 3.28 and the maximum biosorption of MB dye, qmax = 13.20 mg/g, was observed at basic pH values. In the binary system, it was indicated that the MB dye diffuses firstly inside the biosorbent particle and occupies the biosorption sites forming a monodentate complex and then the ARS dye enters and can only bind to untaken sites; forms a tridentate complex with OS active sites. PMID- 26355261 TI - Discussion of "Carbon benefits of wolfberry plantation on secondary saline land in Jingtai oasis, Gansu - A case study on application of the CBP model" by Yaolin Wang, Chuanyan Zhao, Quanlin Ma, Yingke Li, Hujia Jing, Tao Sun, Eleanor Milne, Mark Easter, Keith Paustian, Hoi Wen Au Yong, John McDonagh (2015) [Journal of Environmental Management 157, 303-310]. AB - Wang et al. (2015) employed driving force-pressure-state-impact-response (DPSIR) framework to provide a robust decision-making structure for carbon emission reduction by use of wolfberry plantation in the Jingtai oasis, China. DPSIR appropriately identified the causes of problem along with adopting the responses to the barriers associated with wolfberry plantation. However, the discusser argues that, the paper could have prepared more viable outcomes, if the authors had used causal network rather than causal chains through the DPSIR framework. Furthermore, they could have quantified the mutual relationship among the relevant factors to provide a detailed economic assessment. With this knowledge in hand, the current discussion letter suggests eDPSIR and meDPSIR to address drawbacks regarding conventional DPSIR framework. Due to proper performance of eDPSIR and meDPSIR, they are recommended as practical tools in the future environmental studies. PMID- 26355262 TI - Colloidal PbSe Solar Cells with Molybdenum Oxide Modified Graphene Anodes. AB - With good electrical conductivity, optical transparency, and mechanical compliance, graphene films have shown great potential in application for photovoltaic devices as electrodes. However, photovoltaic devices employing graphene anodes usually suffer from poor hole collection efficiency because of the mismatch of energy levels between the anode and light-harvesting layers. Here, a simple solution treatment and a low-cost solution-processed molybdenum oxide (MoOx) film were used to modify the work function of graphene and the interfacial morphology, respectively, yielding highly efficient hole transfer. As a result, the graphene/MoOx anodes demonstrated low surface roughness and high electrical conductivity. Using the graphene/MoOx anodes in PbSe nanocrystal solar cells, we achieved 1 sun power conversion efficiency of 3.56%. Compared to the control devices with indium tin oxide anodes, the graphene/MoOx-based devices show excellent performance, demonstrating the great potential of the graphene/MoOx anodes for use in optoelectronics. PMID- 26355263 TI - Spike shape analysis of electromyography for parkinsonian tremor evaluation. AB - INTRODUCTION: Standard electromyography (EMG) parameters have limited utility for evaluation of Parkinson disease (PD) tremor. Spike shape analysis (SSA) EMG parameters are more sensitive than standard EMG parameters for studying motor control mechanisms in healthy subjects. SSA of EMG has not been used to assess parkinsonian tremor. This study assessed the utility of SSA and standard time and frequency analysis for electromyographic evaluation of PD-related resting tremor. METHODS: We analyzed 1-s periods of EMG recordings to detect nontremor and tremor signals in relaxed biceps brachii muscle of seven mild to moderate PD patients. RESULTS: SSA revealed higher mean spike amplitude, duration, and slope and lower mean spike frequency in tremor signals than in nontremor signals. Standard EMG parameters (root mean square, median, and mean frequency) did not show differences between the tremor and nontremor signals. CONCLUSIONS: SSA of EMG data is a sensitive method for parkinsonian tremor evaluation. PMID- 26355264 TI - Effects of Natural Organic Matter Properties on the Dissolution Kinetics of Zinc Oxide Nanoparticles. AB - The dissolution of zinc oxide (ZnO) nanoparticles (NPs) is a key step of controlling their environmental fate, bioavailability, and toxicity. Rates of dissolution often depend upon factors such as interactions of NPs with natural organic matter (NOM). We examined the effects of 16 different NOM isolates on the dissolution kinetics of ZnO NPs in buffered potassium chloride solution using anodic stripping voltammetry to directly measure dissolved zinc concentrations. The observed dissolution rate constants (kobs) and dissolved zinc concentrations at equilibrium increased linearly with NOM concentration (from 0 to 40 mg C L( 1)) for Suwannee River humic and fulvic acids and Pony Lake fulvic acid. When dissolution rates were compared for the 16 NOM isolates, kobs was positively correlated with certain properties of NOM, including specific ultraviolet absorbance (SUVA), aromatic and carbonyl carbon contents, and molecular weight. Dissolution rate constants were negatively correlated to hydrogen/carbon ratio and aliphatic carbon content. The observed correlations indicate that aromatic carbon content is a key factor in determining the rate of NOM-promoted dissolution of ZnO NPs. The findings of this study facilitate a better understanding of the fate of ZnO NPs in organic-rich aquatic environments and highlight SUVA as a facile and useful indicator of NOM interactions with metal based nanoparticles. PMID- 26355265 TI - Effects of different sitting positions on skin temperature of the lower extremity. AB - [Purpose] The purpose of this study was to identify the effect of different sitting positions on the skin temperature of the lower extremity. [Subjects] The subjects of this study were 23 healthy university students (8 males, 15 females). [Methods] Normal sitting (NS), upper leg cross (ULC) and ankle on knee (AOK) positions were conducted to measure the changes in skin temperature using digital infrared thermographic imaging (DITI). [Results] ULC upper ankle, NS upper shin, ULC upper shin and NS lower shin showed significant declines in temperature with time. [Conclusion] These finding suggest that the ULC and NS sitting positions cause decline of blood flow volume to the lower extremity resulting in decrease of temperature of the lower extremity. Especially, sitting with the legs crossed interferes with the circulation of blood flowing volume much more than just sitting in a chair. PMID- 26355266 TI - Biomarker-based MicroRNA Therapeutic Strategies for Hepatocellular Carcinoma. AB - Recently, microRNAs (miRNAs) have emerged as key factors involved in a series of biological processes, ranging from embryogenesis to programmed cell death. Its link to aberrant expression profiles has rendered it a potentially attractive tool for the diagnosis, prognosis, or treatment of various diseases. Accumulating evidence has indicated that miRNAs act as tumor suppressors in hepatocyte malignant transformation by regulating development, differentiation, proliferation, and tumorigenesis. Here, we summarize recent progress in the development of novel biomarker-based miRNA therapeutic strategies for hepatocellular carcinoma (HCC). PMID- 26355267 TI - Technical advances in endoscopic ultrasound-guided fiducial placement for the treatment of pancreatic cancer. AB - Radiation therapy has an important role in the treatment of locally advanced or metastatic pancreatic cancer and can be used alone or in conjunction with surgery and/or systemic chemotherapy. Because of the challenge of delivering an accurate and optimal radiation dose, image-guided radiation therapy can be used to improve targeting. Fiducial markers can be placed in the tumor and used for localization in patients undergoing image-guided radiation therapy. The safety and feasibility of endoscopic ultrasound (EUS)-guided placement of fiducials has been assessed and reported for the management of pancreatic cancer. We herein review the technique, efficacy, and safety profile of EUS-guided fiducial placement. In addition, we highlight recent advances and technological upgrades in EUS-guided fiducial delivery systems for pancreatic cancer most relevant to practicing gastroenterologists and interventional endoscopists. PMID- 26355268 TI - Association of prediabetes, defined by fasting glucose, HbA1c only, or combined criteria, with the risk of cardiovascular disease in Koreans. AB - BACKGROUND: The aim of the present study was to compare the association between cardiovascular diseases (CVD) and prediabetes defined by either fasting plasma glucose (FPG), HbA1c, or their combination in a Korean population. METHODS: In all, 76 434 South Koreans who voluntarily underwent a general health examination in the Health Screening & Promotion Center (Asan Medical Center) were analyzed after excluding patients with a previous history of CVD. Cardiovascular events and death due to CVD during a median follow-up period of 3.1 years (interquartile range 1.9-4.3 years) were identified from the Nationwide Health Insurance Claims Database and death certificates using ICD-10 codes. RESULTS: Age- and sex adjusted hazard ratios (HRs) for overall CVD events were significantly greater for subjects with prediabetes defined by FPG only (HR 1.19; 95% confidence interval [CI] 1.08-1.31), HbA1c only (HR 1.28; 95% CI 1.16-1.42), and combined criteria (HR 1.20; 95% CI 1.09-1.32) compared with the normoglycemic group. After adjusting for multiple conventional risk factors (e.g. hypertension, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, smoking status, family history of CVD, and BMI), the HRs for overall CVD were significantly increased only for participants with prediabetes defined by HbA1c. Age- and sex adjusted HRs for major ischemic heart disease events were significantly increased for subjects with prediabetes defined either by HbA1c or combined criteria. Similarly, age- and sex-adjusted HRs for percutaneous coronary intervention were significantly higher for subjects with prediabetes defined by HbA1c only. For diabetes, the multivariate-adjusted HRs for all outcomes were significantly increased by all three criteria. CONCLUSIONS: Adding an HbA1c criterion when defining prediabetes in Koreans can help identify individuals with an increased risk of CVD. PMID- 26355269 TI - Solvated Electrons in Clusters: Magic Numbers for the Photoelectron Anisotropy. AB - This paper reports on a curiosity concerning magic numbers in neutral molecular clusters, namely on magic numbers related to the photoelectron anisotropy in angle-resolved photoelectron spectra. With a combination of density functional calculations and experiment, we search for magic numbers in Na(H2O)n, Na(NH3)n, Na(CH3OH)n, and Na(CH3OCH3)n clusters. In clusters of high symmetry, the highest occupied molecular orbital can be delocalized over an extended region, forming a symmetric charge distribution of high s character, which results in a pronounced anisotropy in the photoelectron angular distribution. We find magic numbers at n = 6 and 4 for sodium-doped dimethyl ether and ammonia clusters, respectively, but not for sodium-doped water and methanol clusters, which is likely a consequence of the degree of hydrogen bonding and the number of structural isomers. PMID- 26355270 TI - Simultaneous determination of imigliptin and its three metabolites in human plasma and urine by liquid chromatography coupled to tandem mass spectrometry. AB - A specific and sensitive method was firstly developed using high performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) to simultaneously quantify imigliptin (KBP-3853) and its three metabolites (KBP 3926, KBP-3902, KBP-5493) in human plasma and urine. Solid-phase extraction (SPE) and direct dilution were used to extract imigliptin and its three metabolites from plasma and urine, respectively. The extracts were injected onto a SymmetryShield RP8 column with a gradient elution of acetonitrile and water containing 5mM ammonium acetate (pH 7). Ionization of KBP-3853, KBP-3926, KBP 3902, KBP-5493, and XZP-3244 (internal standard, IS) was performed using an electrospray ionization (ESI) source in positive mode and detection was carried out with multiple reaction monitoring (MRM) mode. The lower limits of quantitation (LLOQ) of KBP-3853/KBP-3926/KBP-3902/KBP-5493 in human plasma and urine were 0.500/0.500/0.500/0.500ng/mL and 20.0/20.0/10.0/10.0ng/mL, respectively. Inter- and intra-batch precision of imigliptin and its three metabolites were less than 15% and the accuracy was within 85-115% for both plasma and urine. The extraction recoveries of all analytes at three concentration levels were consistent. The specificity, matrix effect, linearity and stabilities under various conditions were validated for imigliptin and its three metabolites in human plasma and urine. In conclusion, the validation results showed that this method was robust, specific, and sensitive and it can successfully fulfill the requirement of clinical pharmacokinetic study of imigliptin hydrochloride in Chinese healthy subjects. PMID- 26355271 TI - Determination of 12 urinary phthalate metabolites in Norwegian pregnant women by core-shell high performance liquid chromatography with on-line solid-phase extraction, column switching and tandem mass spectrometry. AB - Phthalates (dialkyl or alkyl phenyl esters of phthalic acid, benzene-1.2 dicarboxylic acid) are a group of industrial chemicals that have been used for more than 50 years. Phthalates are ubiquitous and can potentially have adverse effects on humans. The present study presents an accurate, sensitive and automated analytical method for measuring 12 phthalate metabolites (free and conjugated) in human urine using on-line solid phase extraction coupled to high performance liquid chromatography - electrospray ionization - tandem mass spectrometry. A small volume of urine sample (300MUL) is required. Glucoronidated phthalate metabolites are deconjugated by incubation with glucoronidase enzyme (Escherihia coli-K 12) and the reaction is stopped by adding formic acid. This is the only sample preparation needed prior to injection into the column switching system. Thus, the method involves minimal sample handling and minimizes possible contaminations from the surroundings. The method was validated by spiking synthetic urine at 5-8 levels in the range of 0.1-500ng phthalate metabolites/mL synthetic urine. The method is sensitive with limits of detection in the low nanogram range, and rapid with a total run time about 25min. The accuracy was between 90 and 120 % and the intermediate precision was given as relative standard deviation was below 20% for most of the compounds. The high sensitivity, high throughput and minimal manual handling make the method suitable for large scale biomonitoring studies. The present method was applied for the determination of phthalate metabolites in urine samples from 116 pregnant women, a subproject within the Norwegian Mother and Child Cohort Study. Concentrations of all the twelve phthalate metabolites was >LOQ in 100% of the samples analysed. Mean urinary concentrations for different phthalate metabolites ranged from 1 to 100ng/mL, the highest concentrations were observed for di-2-ethylhexyl phthalate (DEHP) metabolites and lowest for di-iso-nonyl phthalate (DiNP) metabolites. The urinary concentrations for most of the phthalate metabolites in the present study were found to be in the same range as found in other studies of pregnant women. PMID- 26355272 TI - Current Situation of Postmenopausal Grandmothers Raising Their Grandchildren. AB - As the average life expectancy of women increases, the family and social roles of postmenopausal women have become more important. With the growing number of dual income households, postmenopausal grandmothers occupy a large role in child rearing. Postmenopausal women mainly experience social changes as a family member along with personal changes. Postmenopausal women face changes in physical and mental aspects due to drastic hormonal changes. Grandmothers sharing the burden of raising children are actually encountering a number of challenges while dealing with hardships to adapt to physical and mental changes at the same time. It is thought to be important to understand the impact of raising grandchildren on physical and mental conditions among grandmothers experiencing hardships between social reality and personal changes from medical perspective based on sociological studies. Focusing mainly on studies on related fields, this study aims to investigate personal and social supports from medical perspective and to device practical measures. PMID- 26355273 TI - Riboflavin and ultraviolet A as adjuvant treatment against Acanthamoeba cysts. AB - BACKGROUND: Experimental studies have shown that the standard dose of riboflavin (R) or R + ultraviolet-A (UVA) as solo treatment are not able to exterminate Acanthamoeba cysts or even trophozoites. The purpose of this study is to determine whether the application of R + UVA can enhance the cysticidal effects of cationic antiseptic agents in vitro. METHODS: The log of either polyhexamethylene biguanide or chlorhexidine minimal cysticidal concentration in solutions containing riboflavin (concentrations 0.1, 0.05 and 0.025%) plus either Acanthamoeba castellanii cysts or Acanthamoeba polyphaga cysts was determined and compared in groups treated with UVA 30 mW/cm(2) for 30 min and in control groups (with no exposure to UVA). A permutation test was used to determine the P value associated with treatment. RESULTS: Regardless of the riboflavin concentration and UVA treatment condition, no trophozoites were seen in plates where the cysts were previously exposed to cationic antiseptic agent concentrations >=200 ug/mL for Acanthamoeba castellanii samples and >=100 ug/mL for A. polyphaga samples. There was no statistical evidence that R + UVA treatment was associated with minimal cysticidal concentration (P = 0.82). CONCLUSION: R + UVA in doses up to 10 times higher than recommended for corneal crosslinking does not enhance the cysticidal effect of either polyhexamethylene biguanide or chlorhexidine in vitro. PMID- 26355274 TI - Development of Tivantinib as Treatment for Hepatocellular Carcinoma. AB - Hepatocellular carcinoma (HCC) is a rapidly rising cause of liver-related death worldwide. Most patients are diagnosed at an advanced stage of disease, when systemic therapy is the only viable option for treatment. Significant strides have been made in the molecular understanding of HCC development and growth stimulation. The c-Met pathway has been found to be an important pathway in half of all patients with HCC. HCC tumors with high c-Met activation are associated with an aggressive phenotype and poor prognosis. Tivantinib is a MET receptor tyrosine kinase inhibitor with a broad spectrum of anti-tumor effects currently being studied for the treatment of HCC. Phase I and II data are available for tivantinib in the treatment of solid tumors, including HCC. There appears to be an adequate safety profile, with the main side-effect being neutropenia. In HCC patients with elevated c-Met activity, tivantinib results in an improved time to progression of 2.7 months, compared with 1.4 months in placebo-treated patients. Further studies are ongoing, but early data suggest that tivantinib is a therapy that deserves close attention in the coming years for patients with HCC. PMID- 26355275 TI - Multiprofessional follow-up programmes are needed to address psychosocial, neurocognitive and educational issues in children with brain tumours. AB - AIM: The aim of this study was to coordinate the structured psychosocial, neurocognitive and educational follow-up of children treated for brain tumours with the medical protocol and apply the model in two Swedish healthcare regions. METHODS: We invited all children living in the two regions, who had been diagnosed with a brain tumour from October 1, 2010, through June 30, 2012, to participate along with their parents. The follow-up programme evaluated the emotional status of the parents and patients and assessed the children's general cognitive level, working memory, speed of performance, executive functions and academic achievement from diagnosis through to adult care. RESULTS: During the study period, 61 children up to the age of 17.1 years were diagnosed with a brain tumour, but 18 of these were excluded for various reasons. The majority of the mothers (70%) displayed significantly poor emotional status, as did 34% of the fathers and 21% of the children. The majority of the children (57%) also showed poor neurocognitive performance and needed special adaptations at school (66%). CONCLUSION: Our findings indicate the need for coordinated, multiprofessional follow-up programmes, well anchored in the healthcare organisation, for children diagnosed with brain tumours. PMID- 26355276 TI - Multiple Mutations Detected Preoperatively May Predict Aggressive Behavior of Papillary Thyroid Cancer and Guide Management--A Case Report. AB - BACKGROUND: Multiple gene mutations in thyroid nodules are rare. The presence of several oncogenic mutations could be associated with aggressive biological behavior of tumors. PATIENT FINDINGS: A 60-year-old female presented to her physician after she felt a lump in her neck. On ultrasound, she was found to have a 1.4 cm * 0.8 cm * 1.3 cm nodule in the isthmus and a 0.5 cm * 0.6 cm * 0.6 cm nodule with irregular margins and hypoechogenicity in the right thyroid lobe, warranting fine-needle aspiration (FNA). Cytological examination of the smaller nodule yielded a diagnosis of atypia of undetermined significance (AUS/FLUS, Bethesda Category III). The aspirate was submitted for molecular testing using the next-generation sequencing ThyroSeq((r)) v2 panel. The test revealed four distinct mutations: BRAF (p.V600E), TERT (C228T), PIK3CA (p.H1047R), and AKT1 (p.E17K). Presence of multiple oncogenic mutations in the FNA specimen was highly indicative of cancer, and suggestive of a cancer with propensity toward more aggressive biological behavior. Four weeks after the FNA results were available, the patient underwent total thyroidectomy. This was followed by radioactive iodine ablation after the final pathology revealed a 0.5 cm papillary thyroid carcinoma (PTC) with extrathyroidal extension and positive resection margins (pT3 stage). SUMMARY: Herein, the first case of four mutations preoperatively detected in a subcentimeter thyroid nodule that was confirmed to be a PTC with aggressive biological behavior is reported. CONCLUSIONS: The judicious indication of FNA and use of molecular screening can potentially help in predicting aggressive behavior of small-sized thyroid cancers and in identifying patients who may benefit from early and more extensive therapy. PMID- 26355277 TI - Migrating songbirds on stopover prepare for, and recover from, oxidative challenges posed by long-distance flight. AB - Managing oxidative stress is an important physiological function for all aerobic organisms, particularly during periods of prolonged high metabolic activity, such as long-distance migration across ecological barriers. However, no previous study has investigated the oxidative status of birds at different stages of migration and whether that oxidative status depends on the condition of the birds. In this study, we compared (1) energy stores and circulating oxidative status measures in (a) two species of Neotropical migrants with differing migration strategies that were sampled at an autumn stopover site before an ecological barrier; and (b) a species of trans-Saharan migrant sampled at a spring stopover site after crossing an ecological barrier; and (2) circulating oxidative measures and indicators of fat metabolism in a trans-Saharan migrant after stopovers of varying duration (0 8 nights), based on recapture records. We found fat stores to be positively correlated with circulating antioxidant capacity in Blackpoll Warblers and Red eyed Vireos preparing for fall migration on Block Island, USA, but uncorrelated in Garden Warblers on the island of Ponza, Italy, after a spring crossing of the Sahara Desert and Mediterranean Sea. In all circumstances, fat stores were positively correlated with circulating lipid oxidation levels. Among Garden Warblers on the island of Ponza, fat anabolism increased with stopover duration while oxidative damage levels decreased. Our study provides evidence that birds build antioxidant capacity as they build fat stores at stopover sites before long flights, but does not support the idea that antioxidant stores remain elevated in birds with high fuel levels after an ecological barrier. Our results further suggest that lipid oxidation may be an inescapable hazard of using fats as the primary fuel for flight. Yet, we also show that birds on stopover are capable of recovering from the oxidative damage they have accrued during migration, as lipid oxidation levels decrease with time on stopover. Thus, the physiological strategy of migrating songbirds may be to build prophylactic antioxidant capacity in concert with fuel stores at stopover sites before a long-distance flight, and then repair oxidative damage while refueling at stopover sites after long distance flight. PMID- 26355279 TI - Influence of repeated ochratoxin A ingestion on milk production and its carry over into the milk, blood and tissues of lactating cows. AB - An experiment was conducted to investigate the influence of repeated ingestion of ochratoxin A (OTA) on milk production of lactating Holstein cows over 28 days, and the carry-over of OTA from the diets into the milk and tissues of the cows. Nine cows were divided into three groups, labeled OTA5, OTA50 and OTA100, and fed a diet containing 5, 50 and 100 ug OTA/kg of dry matter, respectively. Body weight, feed intake and daily milk yield in cows were not different among the three groups during the OTA-intake period. OTA residues were neither detected in the tissues, such as liver, kidney, muscles, fat and jejunoileum, nor in the milk of any cows in the OTA intake groups. In contrast, a small amount of OTA (0.1 ug/kg) was detected in the blood plasma of one sample in the OTA50 group and multiple samples in the OTA100 group. The results of this study show that the ingestion of diets containing up to 100 ug/kg of OTA over 28 days does not affect feed intake or milk production of cows, and the dietary OTA is not carried over into milk and edible tissues such as the liver, muscles and fat. PMID- 26355278 TI - Relationship between Myocardial Extracellular Space Expansion Estimated with Post Contrast T1 Mapping MRI and Left Ventricular Remodeling and Neurohormonal Activation in Patients with Dilated Cardiomyopathy. AB - OBJECTIVE: Post-contrast T1 values are closely related to the degree of myocardial extracellular space expansion. We determined the relationship between post-contrast T1 values and left ventricular (LV) diastolic function, LV remodeling, and neurohormonal activation in patients with dilated cardiomyopathy (DCM). MATERIALS AND METHODS: Fifty-nine patients with DCM (mean age, 55 +/- 15 years; 41 males and 18 females) who underwent both 1.5T magnetic resonance imaging and echocardiography were enrolled. The post-contrast 10-minute T1 value was generated from inversion time scout images obtained using the Look-Locker inversion recovery sequence and a curve-fitting algorithm. The T1 sample volume was obtained from three interventricular septal points, and the mean T1 value was used for analysis. The N-Terminal pro-B-type natriuretic peptide (NT-proBNP) level was measured in 40 patients. RESULTS: The mean LV ejection fraction was 24 +/- 9% and the post-T1 value was 254.5 +/- 46.4 ms. The post-contrast T1 value was significantly correlated with systolic longitudinal septal velocity (s'), peak late diastolic velocity of the mitral annulus (a'), the diastolic elastance index (Ed, [E/e']/stroke volume), LV mass/volume ratio, LV end-diastolic wall stress, and LV end-systolic wall stress. In a multivariate analysis without NT proBNP, T1 values were independently correlated with Ed (beta = -0.351, p = 0.016) and the LV mass/volume ratio (beta = 0.495, p = 0.001). When NT-proBNP was used in the analysis, NT-proBNP was independently correlated with the T1 values (beta = -0.339, p = 0.017). CONCLUSION: Post-contrast T1 is closely related to LV remodeling, diastolic function, and neurohormonal activation in patients with DCM. PMID- 26355280 TI - Si-nanocrystal/P3HT hybrid films with a 50- and 12-fold enhancement of hole mobility and density: films prepared by successive drop casting. AB - Hybrid silicon nanocrystal (Si-NC)/poly(3-hexylthiophene) (P3HT) films serve as the active layers of quantum dot/polymer hybrid photovoltaics. To achieve effective photovoltaic properties, it is necessary to enhance the charge carrier mobility and carrier density of the P3HT films. A 50- and 12-fold enhancement of the hole mobility and hole density, respectively, was achieved along the out-of plane direction of a Si-NC/P3HT hybrid film, which corresponds to the carrier migration direction between the photovoltaic electrodes. According to time-of flight, electronic absorption, Raman, atomic force microscopy, photoluminescence lifetime, and X-ray diffraction measurements, the significant enhancement of the mobility and density was attributed to both an increase in the P3HT crystallinity and the dissociation efficiency of P3HT excitons on the addition of Si-NCs to the P3HT films. These enhancements were achieved using a film preparation method developed in the present study, which has been named successive drop casting. PMID- 26355281 TI - The dynamics of unentangled polymers during capillary rise infiltration into a nanoparticle packing. AB - Although highly packed polymer nanocomposites (PNCs) are important for a wide array of applications, preparing them remains difficult because of the poor dispersion of NPs at high loading fractions. One method to successfully prepare PNCs with high loadings is through capillary rise infiltration, as previously shown by Huang et al., although the mechanism of polymer infiltration remains largely unknown. We use molecular dynamics simulations to directly simulate the process of capillary rise infiltration, and we show that the polymers follow Lucas-Washburn dynamics. We observe a wetting front that precedes bulk infiltration, and chains belonging to this front are highly adsorbed to NPs. We also investigate the viscosity of the model polymers both globally and locally in supported and free-standing films, and we find reduced viscosity near the surface of the films and increased viscosity near the supporting substrate, similar to the results of local relaxation times. The reduction in the viscosity at the free surface for short, oligomeric polymers is smaller than for higher molecular weight polymers, and the ratio of the surface viscosities is most consistent with the predictions of the Lucas-Washburn equation. Our results introduce the mechanism by which polymers infiltrate a highly packed NP film, which may shed light on better ways to prepare these materials for energy storage applications and protective coatings. PMID- 26355282 TI - Copy number profiling by array comparative genomic hybridization identifies frequently occurring BRCA2-like male breast cancer. AB - Genomic aberrations can be used to subtype breast cancer. In this study, we investigated DNA copy number (CN) profiles of 69 cases of male breast cancer (MBC) by array comparative genomic hybridization (aCGH) to detect recurrent gains and losses in comparison with female breast cancers (FBC). Further, we classified these profiles as BRCA1-like, BRCA2-like or non-BRCA-like profiles using previous classifiers derived from FBC, and correlated these profiles with pathological characteristics. We observed large CN gains on chromosome arms 1q, 5p, 8q, 10p, 16p, 17q, and chromosomes 20 and X. Large losses were seen on chromosomes/chromosome arms 1p, 6p, 8p, 9, 11q, 13, 14q, 16q, 17p, and 22. The pattern of gains and losses in estrogen receptor positive (ER+) MBC was largely similar to ER+ FBC, except for gains on chromosome X in MBC, which were uncommon in FBC. Out of 69 MBC patients, 15 patients (22%) had a BRCA2-like profile, of which 2 (3%) were also BRCA1-like. One patient (1%) was only BRCA1-like; the remaining 53 (77%) patients were classified as non-BRCA-like. BRCA2-like cases were more often p53 accumulated than non-BRCA-like cases (P = 0.014). In conclusion, the pattern of gains and losses in ER+ MBC was largely similar to that of its ER+ FBC counterpart, except for gains on chromosome X in MBC, which are uncommon in FBC. A significant proportion of MBC has a BRCA2-like aCGH profile, pointing to a potentially hereditary nature, and indicating that they could benefit from a drug regimen targeting BRCA defects as in FBC. PMID- 26355283 TI - Management and Outcome of Colorectal Cancer Liver Metastases in Elderly Patients: A Population-Based Study. AB - IMPORTANCE: Surgical resection is standard treatment for patients with colorectal cancer (CRC) liver metastases (LM). Limited data describe practice and outcomes among elderly patients. OBJECTIVE: To describe management and outcomes of surgical resection of CRC LM in elderly patients in routine practice. DESIGN, SETTING, AND PARTICIPANTS: Population-based retrospective cohort study of routine clinical practices in the Canadian province of Ontario. All cases of CRC in Ontario who underwent resection of LM between January 1, 2002, and December 31, 2009, were identified using the population-based Ontario Cancer Registry and included in this study. Complete information about vital status in the Ontario Cancer Registry was available up to December 31, 2012; cause of death was available up to December 31, 2010. Final study analyses were performed March 13, 2015. Surgical resections of CRC LM were identified from hospital admission records. Pathology reports provided details regarding extent of disease and surgical procedure. Patients were classified into 3 age groups: younger than 65 years, 65 to 74 years, and 75 years or older. We describe volume of resected CRC LM as a ratio of incident cases per CRC LM resection. Use of perioperative chemotherapy was identified through linked electronic treatment and physician billing records. Preoperative and postoperative chemotherapy was defined as chemotherapy given within 16 weeks of surgery. MAIN OUTCOMES AND MEASURES: Overall survival and cancer-specific survival measured from time of LM resection. RESULTS: We identified 1310 patients: 710 (54%) younger than 65 years; 414 (32%) 65 to 74 years; and 186 (14%) 75 years or older. Case volumes of CRC LM resection varied substantially across age groups. For patients younger than 65 years, there was 1 resection per 26 incident cases; 65 to 74 years, 1 per 38; and 75 years or older, 1 per 101 (P<.001). Patients less than 65 years of age had a mean of 2.3 lesions; 65 to 74 years, 2.0; and 75 years or older, 1.6 (P<.001). For patients younger than 65 years, mean size of the largest lesion was 4.0 cm; patients 65 to 74 years, 4.4 cm; and 75 years or older, 4.5 cm (P=.04). The likelihood patients younger than 65 years were to undergo a major liver resection of more than 3 segments was 65%; 65 to 74 years, 65%; and 75 years or older, 42% (P=.04). The percentage of patients younger than 65 years who underwent perioperative chemotherapy was 71% (501 of 710); 65 to 74 years, 57% (237 of 414); and 75 years or older, 41% (77 of 186) (P<.001). The incidence of 90-day mortality for patients younger than 65 years was 2% (11 of 710); 65 to 74 years, 5% (20 of 414); and 75 years or older, 8% (14 of 186) (P<.001). Cancer-specific survival at 5 years for patients younger than 65 years of age was 49%; 65 to 74 years, 47%; and 75 years or older, 35% (P<.001). Overall survival for patients younger than 65 years was 49%; 65 to 74 years, 44%; and 75 years or older, 28% (P<.001). CONCLUSIONS AND RELEVANCE: Resection of CRC LM is associated with greater risk of postoperative mortality among elderly patients despite less aggressive treatment. Although the long-term outcomes are inferior to younger patients, a substantial proportion of elderly patients will have long-term survival. PMID- 26355285 TI - Correction to Exploring the Effect of Conjugation Site and Chemistry on the Immunogenicity of an anti-Group B Streptococcus Glycoconjugate Vaccine Based on GBS67 Pilus Protein and Type V Polysaccharide. PMID- 26355284 TI - Puzzling rocks and complicated clocks: how to optimize molecular dating approaches in historical phytogeography. PMID- 26355286 TI - Corrigendum to "Improvement of regressive autism symptoms in a child with TMLHE deficiency following carnitine supplementation". PMID- 26355289 TI - Young Italian clinician wins Opitz award: Winner details evidence that conditions involving hypermobility are one entity. PMID- 26355290 TI - American society of human genetics updates guidance on genetic testing in children: Group addresses predictive genetic testing, use of secondary findings from genomic sequencing tests. PMID- 26355291 TI - Plasma Proendothelin-1 as an Early Marker of Bronchopulmonary Dysplasia. AB - BACKGROUND: Bronchopulmonary dysplasia (BPD) is a common complication in preterm infants. Clinical prediction of BPD at an early stage in life is difficult. Plasma proendothelin-1 (CT-proET-1) is a lung injury biomarker in pulmonary hypertension and respiratory distress. OBJECTIVE: To assess the prognostic ability of CT-proET-1 in BPD. METHODS: In 227 prospectively enrolled preterm infants born at <32 weeks gestational age (GA), plasma CT-proET-1 was measured at birth, day of life (DOL) 2, 3, 6 and 28, and at 36 weeks postmenstrual age (PMA). BPD was defined as mild in infants requiring supplemental oxygen at DOL 28 and moderate/severe in those requiring it at 36 weeks PMA. RESULTS: The predictive ability of CT-proET-1 for any BPD was poor at birth [area under the ROC curve (AUC) 0.654, 95% CI 0.494-0.814], moderate at DOL 2 and 3 (AUC 0.769, 95% CI 0.666-0.872) and excellent at DOL 6 (AUC 0.918, 95% CI 0.840-0.995). Multivariable regression analysis revealed that CT-proET-1 levels at DOL 2, 3, 6 and 28 were strongly related to the duration of oxygen supplementation, independently of GA and the duration of respiratory support. CONCLUSIONS: CT proET-1 is a novel promising biomarker for predicting the development of BPD in preterm infants when measured at the end of the first week of life. PMID- 26355292 TI - Social Feedback and the Emergence of Rank in Animal Society. AB - Dominance hierarchies are group-level properties that emerge from the aggression of individuals. Although individuals can gain critical benefits from their position in a hierarchy, we do not understand how real-world hierarchies form. Nor do we understand what signals and decision-rules individuals use to construct and maintain hierarchies in the absence of simple cues such as size or spatial location. A study of conflict in two groups of captive monk parakeets (Myiopsitta monachus) found that a transition to large-scale order in aggression occurred in newly-formed groups after one week, with individuals thereafter preferring to direct aggression more frequently against those nearby in rank. We consider two cognitive mechanisms underlying the emergence of this order: inference based on overall levels of aggression, or on subsets of the aggression network. Both mechanisms were predictive of individual decisions to aggress, but observed patterns were better explained by rank inference through subsets of the aggression network. Based on these results, we present a new theory, of a feedback loop between knowledge of rank and consequent behavior. This loop explains the transition to strategic aggression and the formation and persistence of dominance hierarchies in groups capable of both social memory and inference. PMID- 26355293 TI - Intraspecific Phenotypic Variation and Morphological Divergence of Strains of Folsomia candida (Willem) (Collembola: Isotomidae), the "Standard" Test Springtaill. AB - We describe and compare the external morphology of eleven clonal strains and one sexual lineage of the globally distributed Folsomia candida, known as "standard" test Collembola. Of the 18 morphological characters studied, we measured 14 to have significant between-strains genetic variations, 9 of these had high heritabilities (>78%). The quantified morphological polymorphism was used to analyse the within-species relationships between strains by using both a parsimony analysis and a distance tree. These two detailed morphological phylogenies have revealed that the parthenogenetic strains grouped themselves into two major clades. However the exact position of the sexual strain remains unclear and further analysis is needed to confirm its exact relationship with the parthenogenetic ones. The two morphologically based clades were found to be the same as the ones previously described using molecular analysis. This shows that despite large within-strain variations, morphological characters can be used to differentiate some strains that have diverged within a single morphospecies. We discuss the potential evolutionary interpretations and consequences of these different levels of phenotypic variability. PMID- 26355294 TI - New Data on the Clevosaurus (Sphenodontia: Clevosauridae) from the Upper Triassic of Southern Brazil. AB - The sphenodontian fossil record in South America is well known from Mesozoic and Paleogene deposits of Argentinean Patagonia, mainly represented by opisthodontians, or taxa closely related to the modern Sphenodon. In contrast, the Brazilian fossil record is restricted to the Caturrita Formation, Late Triassic of Rio Grande do Sul, represented by several specimens of Clevosauridae, including Clevosaurus brasiliensis Bonaparte and Sues, 2006. Traditionally, Clevosauridae includes several Late Triassic to Early Jurassic taxa, such as Polysphenodon, Brachyrhinodon, and Clevosaurus, the latter well-represented by several species. The detailed description of the specimen MCN-PV 2852 allowed the first systematic revision of most Clevosaurus species. Within Clevosauridae, Polysphenodon is the most basal taxon, and an IterPCR analysis revealed Brachrhynodon as a possible Clevosaurus; C. petilus, C. wangi, and C. mcgilli as possibly distinct taxonomic entities; and the South African Clevosaurus sp. is not closely related to C. brasiliensis. These data indicate the need of a deep phylogenetic review of Clevosauridae, in order to discover synapomorphic characters among the diversity of these Triassic/Jurassic sphenodontians. PMID- 26355295 TI - Inactivated Eyedrop Influenza Vaccine Adjuvanted with Poly(I:C) Is Safe and Effective for Inducing Protective Systemic and Mucosal Immunity. AB - The eye route has been evaluated as an efficient vaccine delivery routes. However, in order to induce sufficient antibody production with inactivated vaccine, testing of the safety and efficacy of the use of inactivated antigen plus adjuvant is needed. Here, we assessed various types of adjuvants in eyedrop as an anti-influenza serum and mucosal Ab production-enhancer in BALB/c mice. Among the adjuvants, poly (I:C) showed as much enhancement in antigen-specific serum IgG and mucosal IgA antibody production as cholera toxin (CT) after vaccinations with trivalent hemagglutinin-subunits or split H1N1 vaccine antigen in mice. Vaccination with split H1N1 eyedrop vaccine antigen plus poly(I:C) showed a similar or slightly lower efficacy in inducing antibody production than intranasal vaccination; the eyedrop vaccine-induced immunity was enough to protect mice from lethal homologous influenza A/California/04/09 (H1N1) virus challenge. Additionally, ocular inoculation with poly(I:C) plus vaccine antigen generated no signs of inflammation within 24 hours: no increases in the mRNA expression levels of inflammatory cytokines nor in the infiltration of mononuclear cells to administration sites. In contrast, CT administration induced increased expression of IL-6 cytokine mRNA and mononuclear cell infiltration in the conjunctiva within 24 hours of vaccination. Moreover, inoculated visualizing materials by eyedrop did not contaminate the surface of the olfactory bulb in mice; meanwhile, intranasally administered materials defiled the surface of the brain. On the basis of these findings, we propose that the use of eyedrop inactivated influenza vaccine plus poly(I:C) is a safe and effective mucosal vaccine strategy for inducing protective anti-influenza immunity. PMID- 26355296 TI - Rapid Molecular Detection of Multidrug-Resistant Tuberculosis by PCR-Nucleic Acid Lateral Flow Immunoassay. AB - Several existing molecular tests for multidrug-resistant tuberculosis (MDR-TB) are limited by complexity and cost, hindering their widespread application. The objective of this proof of concept study was to develop a simple Nucleic Acid Lateral Flow (NALF) immunoassay as a potential diagnostic alternative, to complement conventional PCR, for the rapid molecular detection of MDR-TB. The NALF device was designed using antibodies for the indirect detection of labeled PCR amplification products. Multiplex PCR was optimized to permit the simultaneous detection of the drug resistant determining mutations in the 81-bp hot spot region of the rpoB gene (rifampicin resistance), while semi-nested PCR was optimized for the S315T mutation detection in the katG gene (isoniazid resistance). The amplification process additionally targeted a conserved region of the genes as Mycobacterium tuberculosis (Mtb) DNA control. The optimized conditions were validated with the H37Rv wild-type (WT) Mtb isolate and Mtb isolates with known mutations (MT) within the rpoB and katG genes. Results indicate the correct identification of WT (drug susceptible) and MT (drug resistant) Mtb isolates, with the least limit of detection (LOD) being 104 genomic copies per PCR reaction. NALF is a simple, rapid and low-cost device suitable for low resource settings where conventional PCR is already employed on a regular basis. Moreover, the use of antibody-based NALF to target primer labels, without the requirement for DNA hybridization, renders the device generic, which could easily be adapted for the molecular diagnosis of other infectious and non-infectious diseases requiring nucleic acid detection. PMID- 26355297 TI - A Three-Dimensional Skeletal Reconstruction of the Stem Amniote Orobates pabsti (Diadectidae): Analyses of Body Mass, Centre of Mass Position, and Joint Mobility. AB - Orobates pabsti, a basal diadectid from the lower Permian, is a key fossil for the understanding of early amniote evolution. Quantitative analysis of anatomical information suffers from fragmentation of fossil bones, plastic deformation due to diagenetic processes and fragile preservation within surrounding rock matrix, preventing further biomechanical investigation. Here we describe the steps taken to digitally reconstruct MNG 10181, the holotype specimen of Orobates pabsti, and subsequently use the digital reconstruction to assess body mass, position of the centre of mass in individual segments as well as the whole animal, and study joint mobility in the shoulder and hip joints. The shape of most fossil bone fragments could be recovered from micro-focus computed tomography scans. This also revealed structures that were hitherto hidden within the rock matrix. However, parts of the axial skeleton had to be modelled using relevant isolated bones from the same locality as templates. Based on the digital fossil, mass of MNG 10181 was estimated using a model of body shape that was varied within a plausible range to account for uncertainties of the dimension. In the mean estimate model the specimen had an estimated mass of circa 4 kg. Varying of the mass distribution amongst body segments further revealed that Orobates carried most of its weight on the hind limbs. Mostly unrestricted joint morphology further suggested that MNG 10181 was able to effectively generate propulsion with the pelvic limbs. The digital reconstruction is made available for future biomechanical studies. PMID- 26355298 TI - Predicting Response to Neoadjuvant Chemotherapy with PET Imaging Using Convolutional Neural Networks. AB - Imaging of cancer with 18F-fluorodeoxyglucose positron emission tomography (18F FDG PET) has become a standard component of diagnosis and staging in oncology, and is becoming more important as a quantitative monitor of individual response to therapy. In this article we investigate the challenging problem of predicting a patient's response to neoadjuvant chemotherapy from a single 18F-FDG PET scan taken prior to treatment. We take a "radiomics" approach whereby a large amount of quantitative features is automatically extracted from pretherapy PET images in order to build a comprehensive quantification of the tumor phenotype. While the dominant methodology relies on hand-crafted texture features, we explore the potential of automatically learning low- to high-level features directly from PET scans. We report on a study that compares the performance of two competing radiomics strategies: an approach based on state-of-the-art statistical classifiers using over 100 quantitative imaging descriptors, including texture features as well as standardized uptake values, and a convolutional neural network, 3S-CNN, trained directly from PET scans by taking sets of adjacent intra tumor slices. Our experimental results, based on a sample of 107 patients with esophageal cancer, provide initial evidence that convolutional neural networks have the potential to extract PET imaging representations that are highly predictive of response to therapy. On this dataset, 3S-CNN achieves an average 80.7% sensitivity and 81.6% specificity in predicting non-responders, and outperforms other competing predictive models. PMID- 26355299 TI - Differing brain structural correlates of familial and environmental risk for major depressive disorder revealed by a combined VBM/pattern recognition approach. AB - BACKGROUND: Neuroimaging traits of either familial or environmental risk for major depressive disorder (MDD) have been interpreted as possibly useful vulnerability markers. However, the simultaneous occurrence of familial and environmental risk might prove to be a major obstacle in the attempt of recent studies to confine the precise impact of each of these conditions on brain structure. Moreover, the exclusive use of group-level analyses does not permit prediction of individual illness risk which would be the basic requirement for the clinical application of imaging vulnerability markers. Hence, we aimed to distinguish between brain structural characteristics of familial predisposition and environmental stress by using both group- and individual-level analyses. METHOD: We investigated grey matter alterations between 20 healthy control subjects (HC) and 20 MDD patients; 16 healthy first-degree relatives of MDD patients (FH+) and 20 healthy subjects exposed to former childhood maltreatment (CM+) by using a combined VBM/pattern recognition approach. RESULTS: We found similar grey matter reductions in the insula and the orbitofrontal cortex in patients and FH+ subjects and in the hippocampus in patients and CM+ subjects. No direct overlap in grey matter alterations was found between FH+ and CM+ subjects. Pattern classification successfully detected subjects at risk for the disease even by strictly focusing on morphological traits of MDD. CONCLUSIONS: Familial and environmental risk factors for MDD are associated with differing morphometric anomalies. Pattern recognition might be a promising instrument in the search for and future application of vulnerability markers for MDD. PMID- 26355301 TI - Gene Therapy Briefs. PMID- 26355300 TI - Hepatitis B and Hepatitis C Reactivation in the Biologic Era. AB - Hepatitis B (HBV) and hepatitis C (HCV) reactivation may occur after the use of biologic agents. During the last decade, utilization of biologics has changed the fate of many treated for cancer, autoimmune and connective tissue disease, maintenance of transplanted organs, and the prevention of graft-versus-host disease among others. HBV reactivation has been reported in up to 50% of HBV carriers undergoing immunosuppressive therapy, and there is emerging data pointing towards an increased risk for HCV reactivation. If reactivation of HBV and HCV occurs, the spectrum of clinical manifestations can range from asymptomatic hepatitis flares to hepatic decompensation, fulminant hepatic failure, and death. Therefore, identifying patients at risk and early diagnosis are imperative to decrease significant morbidity and mortality. The purpose of this article is to review the pathophysiology of the reactivation of HBV and HCV infection in patients receiving biologic therapies and the approaches used to diagnose, prevent, and treat HBV and HCV reactivation. PMID- 26355303 TI - Residual metals present in "metal-free" N-doped carbons. AB - To date, "metal-free" catalysts originating from graphene and CNTs have been revealed to contain metal impurities. Many types of such "metal-free" carbons have been synthesized by metal-involving methods, and it is urgent to confirm the origin of the catalytic performance. Herein, we verified that residual metals were inevitably present in these N-doped carbons and the catalytic performance for the hydrogen evolution reaction (HER) was due to the remaining metals, present at only a ppm level. PMID- 26355304 TI - Quantification of Training and Competition Load Across a Season in an Elite Australian Football Club. AB - PURPOSE: Load monitoring in Australian football (AF) has been widely adopted, yet team-sport periodization strategies are relatively unknown. The authors aimed to quantify training and competition load across a season in an elite AF team, using rating of perceived exertion (RPE) and GPS tracking. METHODS: Weekly totals for RPE and GPS loads (including accelerometer data; PlayerLoad) were obtained for 44 players across a full season for each training modality and for competition. General linear mixed models compared mean weekly load between 3 preseason and 4 in-season blocks. Effects were assessed with inferences about magnitudes standardized with between-players SD. RESULTS: Total RPE load was most likely greater during preseason, where the majority of load was obtained via skills and conditioning. There was a large reduction in RPE load in the last preseason block. During in-season, half the total load came from games and the remaining half from training, predominantly skills and upper-body weights. Total distance, high-intensity running, and PlayerLoad showed large to very large reductions from preseason to in-season, whereas changes in mean speed were trivial across all blocks. All these effects were clear at the 99% level. CONCLUSIONS: These data provide useful information about targeted periods of loading and unloading across different stages of a season. The study also provides a framework for further investigation of training periodization in AF teams. PMID- 26355302 TI - Catecholaminergic Fiber Innervation of the Vocal Motor System Is Intrasexually Dimorphic in a Teleost with Alternative Reproductive Tactics. AB - Catecholamines, which include the neurotransmitters dopamine and noradrenaline, are known modulators of sensorimotor function, reproduction, and sexually motivated behaviors across vertebrates, including vocal-acoustic communication. Recently, we demonstrated robust catecholaminergic (CA) innervation throughout the vocal motor system in the plainfin midshipman fish Porichthys notatus, a seasonal breeding marine teleost that produces vocal signals for social communication. There are 2 distinct male reproductive morphs in this species: type I males establish nests and court females with a long-duration advertisement call, while type II males sneak spawn to steal fertilizations from type I males. Like females, type II males can only produce brief, agonistic, grunt type vocalizations. Here, we tested the hypothesis that intrasexual differences in the number of CA neurons and their fiber innervation patterns throughout the vocal motor pathway may provide neural substrates underlying divergence in reproductive behavior between morphs. We employed immunofluorescence (-ir) histochemistry to measure tyrosine hydroxylase (TH; a rate-limiting enzyme in catecholamine synthesis) neuron numbers in several forebrain and hindbrain nuclei as well as TH ir fiber innervation throughout the vocal pathway in type I and type II males collected from nests during the summer reproductive season. After controlling for differences in body size, only one group of CA neurons displayed an unequivocal difference between male morphs: the extraventricular vagal-associated TH-ir neurons, located just lateral to the dimorphic vocal motor nucleus (VMN), were significantly greater in number in type II males. In addition, type II males exhibited greater TH-ir fiber density within the VMN and greater numbers of TH-ir varicosities with putative contacts on vocal motor neurons. This strong inverse relationship between the predominant vocal morphotype and the CA innervation of vocal motor neurons suggests that catecholamines may function to inhibit vocal output in midshipman. These findings support catecholamines as direct modulators of vocal behavior, and differential CA input appears reflective of social and reproductive behavioral divergence between male midshipman morphs. PMID- 26355305 TI - Coinfection by Hepatitis C Is Strongly Associated with Abnormal CD4/CD8 Ratio in HIV Patients under Stable ART in Salvador, Brazil. AB - Proper immune restoration (CD4 count >500 and normal CD4/8 ratio) is reached only by a fraction of HIV patients, despite stable viral suppression. METHODS: We present a case-control study to compare HIV patients with viral suppression >1 year, according to immune restoration pattern: adequate response (AR) defined by CD4 > 500 cells/mm(3) and CD4/8 ratio >1; partial response (PR = patients with CD4 > 500, but CD4/8 ratio <1); inadequate response (IR = CD4 < 500 cells). RESULTS: We evaluated 293 consecutive patients (89 AR, 112 PR, and 92 IR), 70% males. Male gender (p < 0.01), lower mean CD4 nadir (p < 0.001), higher baseline VL (p = 0.01), previous diagnosis of Tb (p = 0.03), or HCV (p < 0.01) was associated with IR. Likelihood of AR/PR was similar regardless of gender, after adjusting for nadir CD4+ cells count. Longer time under suppressive ART was also associated with a greater chance of AR, but logistic regression identified coinfection by HCV as the main factor associated with abnormal CD4/CD8 ratio. CONCLUSION: Early initiation of ART and longer time since first undetectable PVL were predictors of AR. Previous HCV diagnosis significantly increases the risk of abnormal CD4/CD8 ratio. PMID- 26355306 TI - Effects of the application of Low-Dye taping on the pain and stability of patients with plantar fasciitis. AB - [Purpose] This study examined how the application of Low-Dye (LD) taping affected the pain and stability of patients with plantar fasciitis. [Subjects] The subjects were 30 patients with plantar fasciitis who were divided into two groups: a Low-Dye taping group (LTG, n=15) and a conservative treatment group (CTG, n=15). [Methods] The treatments were performed three times a week for six weeks in both groups. A visual analog scale (VAS) was used to evaluate the pain and stability of patients with plantar fasciitis, and the transfer area of the center of gravity (TAOCOG) was measured to evaluate stability using a BioRescue device. [Results] In the within-group comparison of the VAS, the LTG and CTG values significantly decreased. In the post-test between-group comparison, the VAS pain decreased more significantly in LTG than in CTG. In the within-group comparison of the TAOCOG, the LTG value significantly increased. In the post-test between-group comparison, the TAOCOG value increased more significantly than in LTG than in CTG. [Conclusion] Utilizing Low-Dye taping for patients with plantar fasciitis appears to be an effective intervention method for reducing pain and enhancing stability. PMID- 26355307 TI - SURGICAL TREATMENT OF UPPER AND MIDDLE FACIAL ZONE TRAUMAS IN PROGRESS OF CONCOMITANT TRAUMATIC CRANIOFACIAL INJURIES. AB - In 2012-2015, 207 patients with concomitant craniofacial injuries, who underwent surgical treatment, were observed; among them 176 were men and 31- women. Age of the patients ranged from 16 to 60 years. According to localization and severity of trauma and a priority of surgical intervention, the patients conventionally were divided into 3 groups by the authors: I group (65 patients) - craniofacial injuries; the skull as well as upper and middle areas of face (subcranial and frontobasal fractures) were affected (fractured). II group (80 patients) - severe traumatic injuries of upper and especially middle zones of the face, accompanied with closed craniocerebral trauma, no need in neurosurgery. III group (62 patients) -on the background of serious head traumas, the injuries of face bones were less severe (injury of one or two anatomic areas with displacement of fractured fragments but without bone tissue defects) According to the obtained results a priority was always given to the neurosurgery (vital testimony).The reconstructive surgeries on face skeleton was conducted in combination involving neurosurgeons (I group patients). Reconstructive surgeries of facial bones were conducted in the patients of II group, immediately or at primary deferred period of time but in the patients of III group the surgical procedures for removal of early secondary or traumatic residual fractures have been performed. Reposition of the fractured facial bone fragments was performed in an open way and fixation was carried out by titanium plates and mesh cage (at bone tissue defect). For prevention and elimination of post-traumatic inflammatory processes, the final stage of surgical intervention was: sanation of nasal accessory sinuses and catheterization (5-7 days) of external carotid arteries for administration of antibiotics and other medical preparations. Early and differentiated approach to face injuries, worsening in the course of craniocephalic trauma was not revealed in any patient; there was no evidence of development inflammatory processes in traumatic regions; esthetic and functional results obtained after the surgeries of maxillofacial area were assessed as good and satisfactory. PMID- 26355308 TI - CESARIAN SECTION - HIGHER RATE AND HIGHER CHALLENGES. AB - There is evidence that perinatal morbidity and mortality has not changed - caesarean section rate increased and data remained stable and rate of intro and post operative complications was increased. There is another view of the picture: the right of patient to choose mode of delivery and the reality, that the number of patients with prior caesarian section and number patient and physician prefer caesarean section. The following topics are discussed as well: age of pregnant woman, macrosomia and intrauterine growth restriction, malpresentation, multiple gestation, preeclampsia, BMI, role of assisted reproductive technologies, electronic monitoring of fetal heart rate in labor, induction of labor. Private sector role and physicians fear of legal issues are also addressed. Postoperative complications are discussed and authors conclude that it is associated with non rational rate of caesarian section. The health sector authorities and physicians must carefully choose the mode of delivery especially in primagravidas. PMID- 26355309 TI - CLINICAL AND ANAMNESTIC CHARACTERISTICS OF DEVELOPMENT OF ANTISPERM IMMUNITY IN INFERTILE MEN. AB - The aim of the research was to establish connection between the roles of infertility duration, patient age, various extragenital and genital pathologies in ASA pathogenesis. The work is based on retrospective analysis of 496 outpatient cards, which covered detailed anamnestic data and results of past complex clinico-laboratory tests. Criteria for inclusion in the study was infertility during marriage for at least 18 month, high concentration of ASA-s in booth blood and sperm. It was found that there is no statistically significant connection between the ASA and past illnesses, profession, family history, accompanying autoimmune diseases and extragenital pathologies. Chlamydia trachomatis, Ureaplasma urealyticum, and Mycoplasma hominis compared to other STDs, cause statistically significant increase of ASAs concentration in blood serum, as well as in ejaculate (p<0,001). Testicle associated pathologies plays an important role in development of antisperm immunity, especially orchitis and epididymitis, during which statistically insignificant increase of levels of ASA has been detected in blood, as well as in semen (p<0,001). Thus, we can conclude that, Chlamydia trachomatis, Ureaplasma urealyticum, Mycoplasma hominis, orchitis and epididymitis causes malfunction of blood-testicular barrier, which resulted in inflammatory and toxic damage of spermatogenic epithelium, which in turn plays significant role in the development of autoimmune infertility. PMID- 26355310 TI - [CORRELATION MATRIX OF CHARACTERISTICS OF CHRONIC RECURRENT APHTHOUS STOMATITIS]. AB - The purpose of the present work is to study the correlation between the risk factors of chronic recurrent aphthous stomatitis. The research was conducted on 62 patients between ages of 40 and 70 years at Tbilisi Hospital for Veterans of War. The analysis was carried out by Spearman's Rank Correlation method using the statistical package SPSS 11.5. We investigated: harmful habits, professional factors, background and accompanying illnesses, pathology of teeth, focal infection, emotional stress, genetic factors. Correlation matrix between the significant risk factors of chronic recurrent aphthous stomatitis is defined. Multiple correlations have the following factors: industrial dust, focal infections, emotional stress, anemia. Correlation diagram of etiological factors of chronic recurrent aphthous stomatitis is helpful for providing professional and expert services. PMID- 26355311 TI - [MORPHOGENESIS OF THE ANODERM STRUCTURAL CHANGES IN PATIENTS WITH CHRONIC ANAL FISSURES]. AB - The objective of the study is to find peculiarities of the anoderm structural changes of morphogenesis in patients with chronic anal fissures (CAF) for further substantiation of therapeutic methods. The material of the study was the tissues of dissected anal complex (bottom and margins of ulcer, hypertrophic anal papilla, sentinel pile) from 33 patients. Histological examination found the defect of the stratified squamous epithelium. The epidermis of the marginal area of the wound, hypertrophic with signs of parakeratosis and acanthosis, hanged over the bottom. The surface of the bottom and margins of the wound in 31 cases (94%) was with thickening of rough fibrous masses. The bottom of ulcer in 29 (88%) cases is presented by sclerosed connective tissue. An increased amount of collagen fibers was found forming fuchsinophil is bundles. In 24 (73%) cases the scar on the fuchsine bottom of fissure was 3,4 mm (0,3+/-0,02) in deep. There are separate complexes of newly formed blood vessels with prevailing localization in the lateral walls of the wound. The blood vessels were with main by fibrosis in deep areas of the wound. Moderate interstitial edema and focal interstitial inflammatory infiltration mostly of lymphocytes and fibroblasts were detected; the amount of macrophages was not substantial. Considering cicatrical rebuilding of the anoderm of ulcer bottom caused, first of all, by hypoxia leading to activation of collagen-producing function of fibroblastes and absence of the signs of epithelization, patients with CAF should be treated surgically dissecting the bottom and margins of fissure in the complex with hypertrophic anal papilla and sentinel pile. PMID- 26355312 TI - [ASSESSMENT OF PULMONARY VENTILATION FUNCTION AT INTENSIVE CARE UNIT PATIENTS]. AB - The article presents the functional characteristics of lung tissue in reanimation profile patients with different pathologies with forced ventilation and auxiliary support on the background. The aim of this study was to analyze the dynamics properties of lung tissue in intensive care unit patients with symptoms of severe violations of restrictive lung tissue being on ventilatory support. Results were subjected to analysis of acid-base status and dynamics of the main indicators of the biomechanical properties of the lung in 32 patients with severe concomitant injury (n=21), acute bilateral community-acquired pneumonia (n=7), septic shock (n=4) during the entire period of the respiratory "prosthetics "(before and after the beginning of mechanical ventilation). Using during ventilatory support of patients with initial symptoms of the syndrome of acute lung damage and reduced lung function restrictive positive end-expiratory pressure of 6-10 cm of water column when the conventional (1:2; 1:2.5 at p<=0.05) and invert (2:1 at p<=0,1) ratio inhale/exhale, relatively low tidal volume (6-8 ml/kg) allows increase the compliance of the lung tissue to 11-29%. Increased expiratory time constant has a direct correlation with the value of airway resistance was due not only to the maintenance of optimal parameters for MVV (mechanical voluntary ventilation), but regular lavage of the tracheobronchial tree, which allows to maintain patency of the lower respiratory tract. The main areas during mechanical ventilation of lungs in patients with a sharp decline in restrictive lung function (ARDS, pneumonia), regardless of the reason it was summoned, optimal value is the observance of the positive end-expiratory pressure, the ratio of inhale/exhale (depending on the degree of hypoxemia), to maintain sufficient blood oxygen saturation and partial pressure of oxygen in the blood plasma. PMID- 26355313 TI - PRO12ALA POLYMORPHISM ASSOCIATION OF PPAR-gamma GENE WITH BIOCHEMICAL PARAMETERS OF THE BLOOD IN PATIENTS WITH CHRONIC DIFFUSE LIVER DISEASES. AB - The connection of Pro12Ala polymorphism of PPAR-gamma gene with blood biochemical parameters in patients with nonalcoholic fatty liver disease (NAFLD) and nonviral chronic hepatitis (CH) were analyzed. The frequency of incidence of minor Ala allele of PPAR-gamma gene in those patients was not found to be significantly different from that in healthy individuals. Aspartate aminotransferase activity in NAFLD patients, Ala-allele carriers, was significantly higher on 55,5% (p=0,007) than in patients with Pro/Pro-genotype. At the same time, alanine aminotransferase activity in patients with Ala-allele was significantly higher on 80,0% (p=0,03) than in patients with Pro/Pro -genotype PPAR-gamma gene. In this cohort of patients with minor Ala-allele high gamma-glutamyltransferase activity was diagnosed, which in 2,1 times (p=0,04) prevailed that in patients, Pro/Pro genotype carriers. Patients with CH showed no significant association between Pro12Ala polymorphism of PPAR-gamma gene and activity of biochemical markers of pathological process in the liver. PMID- 26355314 TI - DISTRIBUTION OF THYROID PATHOLOGIES IN DIFFERENT AGE GROUPS IN GEORGIA. AB - We aimed to analyze the diagnostic criteria proposed by the Bethesda System for reporting thyroid Fine needle aspiration biopsy (FNAB) results. FNABs of 600 patients were performed during 1-year period (2013-2014) in Georgian hospitals (Tbilisi Cancer Center, New Hospitals, National Screening Center). Based on our clinical, ultrasound, FNAB and histology results we define how each diagnostic category of the Bethesda System is distributed among age and sex groups of the cases included in this work. The patient age range was from 20- to 80 years and grouped them in four age groups: I group 20-35 years (n=87), II group 36-50 (n=243), III group 51-65 (n=206) and IV group 66-80(n=64). Histologic correlation was made, defined rate of malignancy. Each diagnostic category conveys specific risk of malignancy, which offers guidance for patient management. Our study showed that the probability of benign nodules is high in our cases, encountered 63,3%. Benign nodules are most commonly found in the group II and III, which are middle age groups. Bethesda class 3 or AUS/FLUS category, which is the most heterogeneous class, carries the rate of malignancy 20,4% and most commonly encountered in group II and III. According to our study particularly noteworthy and interesting was the first age group (20-35 years) because most of the diagnosis of Bethesda class 6 or malignant category was encountered in this age group. Based on our data, it should be noted that there are very high probability of cancer in young age group and it carries high risk of malignancy. PMID- 26355315 TI - [VISIBLE LIGHT AND HUMAN SKIN (REVIEW)]. AB - Biological effect of a visible light depends on extend of its property to penetrate into the tissues: the greater is a wavelength the more is an effect of a radiation. An impact of a visible light on the skin is evident by wave and quantum effects. Quanta of a visible radiation carry more energy than infrared radiation, although an influence of such radiation on the skin is produced by the light spectrum on the boarder of the ultraviolet and the infrared rays and is manifested by thermal and chemical effects. It is determined that large doses of a visible light (405-436 nm) can cause skin erythema. At this time, the ratio of generation of free radicals in the skin during an exposure to the ultraviolet and the visible light range from 67-33% respectively. Visible rays of 400-500 nm length of wave cause an increase of the concentration of oxygen's active form and mutation of DNA and proteins in the skin. The urticaria in 4-18% of young people induced by photodermatosis is described. As a result of a direct exposure to sunlight photosensitive eczema is more common in elderly. Special place holds a hereditary disease - porphyria, caused by a visible light. In recent years, dermatologists widely use phototherapy. The method uses polychromatic, non coherent (wavelength of 515-1200 nm) pulsating beam. During phototherapy/light treatment a patient is being exposed to sunlight or bright artificial light. Sources of visible light are lasers, LEDs and fluorescent lamps which have the full range of a visible light. Phototherapy is used in the treatment of acne vulgaris, seasonal affective disorders, depression, psoriasis, eczema and neurodermities. LED of the red and near infrared range also is characterized by the therapeutic effect. They have an ability to influence cromatophores and enhance ATP synthesis in mitochondria. To speed up the healing of wounds and stimulate hair growth light sources of a weak intensity are used. The light of blue-green spectrum is widely used for the treatment of neonatal hyperbilirubinemy. A photodynamic therapy takes a special place. The third generation of the blue (410 nm), yellow (595 nm) and red photosensitors are used. Photodynamic therapy is used in the treatment of cancer as well. PMID- 26355316 TI - MOLECULAR TRACING OF HETEROSEXUAL HIV-1 TRANSMISSION IN GEORGIA. AB - HIV epidemic in Georgia has entered a new phase with number of heterosexually acquired infections rising each year. Epidemiological data indicates that this switch in epidemic trends is largely due to HIV positive male IDUs transmitting the virus to their female sexual partners. However, no genetic studies confirming linkage between IDUs and their sex partners were done in Georgia before. The objective of our study was to investigate molecular epidemiology of HIV-1 transmission events between heterosexual couples. Viral genotypes were obtained from plasma specimens of 36 heterosexual HIV-1 positive antiretroviral treatment (ART) naive persons representing 18 epidemiologically linked transmission events were genotyped and phylogenetic analyses were done on HIV pol sequences. HIV infection among all women was attributed to heterosexual transmission from their partners. None of 18 women had history of IDU. Fourteen pairs had subtype A virus, three - subtype B and one - subtype G viruses. Phylogenetic analysis confirmed the existing epidemiological link in 16 pairs with bootstrap values ranging from 88% to 100%. Of these 16 events, viruses from 14 pairs had genetic distance less than 0.015.Mutation A62V was seen in samples from 5 pairs, of them samples from 4 pairs additionally had V77I mutation. All 5 pairs were infected with the subtype Avirus. Women, who are sexual partners of IDUs or other men with high risk heterosexual behaviors, are at increased risk of HIV acquisition. HIV epidemic in Georgia has not spread to general population and remains concentrated around key populations at risk. Our work confirms that female sexual partners can serve as a bridge between key affected populations and general community, such as heterosexually active adults. Therefore, prevention efforts targeting key populations at risk and their sexual partners need to be expanded to avoid the spread of the infection within specific communities and beyond. PMID- 26355317 TI - THE CAUSES AND SYMPTOMS OF SOMATOFORM DISORDERS IN CHILDREN (REVIEW). AB - The causes of somatoform disorders in children and adolescents and clinical description of various syndromes like hypochondric impairment, non epileptic paroxysmal disorders, chronic fatigue syndrome, trauma and headache are presented in this review. The modern epidemiological evidences of mentioned conditions are also considered which indicate on progressive increase of these diseases for recent 20 years. We have also discussed the standardized methods of prevention, differential diagnosis and treatment of somatoform diseases. PMID- 26355318 TI - THE IMPORTANCE OF EDUCATING PEDIATRICIANS ABOUT PRIMARY IMMUNODEFICIENCY DISORDERS: A TERTIARY HOSPITAL EXPERIENCE. AB - Primary immunodeficiency disorders (PIDs) are several genetic disorders that alter the essential components of the immune system leading to errors in differentiation, function or both of these components.There are more than 200 reported different PID diseases with more than 140 identified gene mutations, affecting almost six million individuals globally, but only 27,000-60,000 have being diagnosed.Early diagnosis of PIDs can markedly reduce morbidity and mortality via proper intervention The aim of the study was to estimate the knowledge and attitude of pediatric residents of PIDs.To the best of our knowledge, this is the first study that targets resident physicians in the field of PIDs. A prospective and cross-sectional study was conducted at Hamad Medical Corporation, the only tertiary care, academic and teaching hospital in the state of Qatar. The study took place between January, 2014 and April 30, 2014. A self administered questionnaire was distributed to 68 pediatric residents (post graduate year 1-4). In all, 68 eligible resident physicians were included in the study. Out of the 68 questionnaires distributed, 59 (86.7%) were returned by the end of the study. Among the participants, 18 (30.5%) were post-graduate year-1 (PGY-1), 18 (30.5%) PGY-2, 11 (18.6%) PGY-3, and 12 (20.3%) PGY-4.The mean overall score was 58.5 %. The mean score in the clinical presentation was 67.5%, in associated syndromes and diseases was 59%, in screening laboratory work up 55.3%, and in the section of laboratory investigations that suggest PIDs 52%. There is a significant lack of knowledge of PIDs among pediatric residents. In addition, a large number of pediatric physicians in training do not feel comfortable in diagnosing and managing young children with PIDs. Pediatric residency working hours rule restrict the luxury of having an allergy/immunology rotation during residency. A mutual effort in sharing diagnosis and management of patients with PIDs between pediatric residents and attending immunologists can ameliorate the lack of knowledge and improve the trainee's confidence when facing such cases. PMID- 26355319 TI - COMPARATIVE STUDY OF GROWTH INHIBITORY PROTEIN COMPLEX DERIVED FROM DIFFERENT FORMS OF CHILDREN HEMANGIOMA. AB - The comparative analysis of the thermostable protein complexes obtained from the capillary and the cavernous hemangioma was carried out. It is shown that the active component (with low molecular weight 12-14 kD) is in minor content in the complexes obtained from capillary, as well as from the cavernous hemangioma. The effect of protein complexes from cavernous hemangiomas on proliferation of the brain and pancreatic cells in growing rats was studied. It was established that the thermostable protein complex from cavernous hemangiomas does not have the ability to inhibit the proliferation of heterotypic cells due to the minor content of the active ingredient in protein complexes. PMID- 26355320 TI - HEPATOCELLULAR CARCINOMA: CURRENT AND PROSPECTIVE IMMUNOTHERAPEUTIC STRATEGIES. AB - Hepatocellular carcinoma (HCC) is a highly lethal and the most common primary liver cancer with increasing worldwide incidence. Pathogenesis of HCC is immune mediated, however, not completely understood. Chronic low-grade inflammation alters both innate and adaptive immune responses. As a result tolerogenic environment is established in damaged organ. Up to date, incomplete understanding of HCC pathogenesis and the extend of biomarker variability among patients represent the major obstacle for early diagnosis and for the choice of effective treatment. Among current treatment options for HCC, thermal ablation strategy, which in addition to cancer eradication provides adjuvant/"danger"signal to the patient's immune cells, has demonstrated its active immunotherapeutic effect. In ongoing phase I/II clinical trials, tumor antigen loaded dendritic cell (DC) based vaccines as well as tumor-specific cytotoxic T cells are being tested. Genetically redirected T cell therapy and more refined autologous vaccines are still awaiting approaches in HCC. The topic of this review focuses on current and bench-to-bedside immunotherapeutic strategies for HCC and discusses their advantages and limitations in clinic. We also weight up several prospective immunotherapeutic approaches which in theory have the potential for further implication in HCC. Combination of the induction of effective antitumor immunity with the inhibition of the mechanisms of tumor-induced immunosuppression ought to be a key objective in these future developments. PMID- 26355321 TI - [MORPHOFUNCTIONAL ADJUSTMENT VASCULAR AND CELLULAR COMPONENTS OF THE CEREBELLAR CORTEX IN EXPOSURE TO BODY SULFATES OF COPPER, ZINC AND IRON]. AB - In order to analyze the morphological and morphometric reconstructions of the vascular bed, and Purkinje cells of the cerebellar cortex of rats in long-term action (for 90 days) on the body of sulphates of copper, zinc and iron, an experiment was conducted on 48 adult white male rats weighing 200-250 g in age 5 7 months. We used anatomical, morphometric, statistical and common methods of microanatomical research. It was found that the combined effect on the body of sulphates of copper and zinc, and iron in the cerebellum has enough expressive toxicity, which affects the condition of the vascular bed, and Purkinje cells. The degree of morphological transformations is in direct proportion to the duration of the experiment. In the pathogenesis of violations leading role played by hypoxia, develop signs of swelling of the cerebellar cortex with signs hemorrhagic infiltration, the severity of which is maximum on the 60th day of the experiment. PMID- 26355322 TI - [CARDIOVASCULAR SYSTEM REACTIVITY IN PRENATALLY STRESSED RATS DURING THE LATE PERIOD OF ONTOGENESIS]. AB - Systolic, diastolic blood pressure and heart rate were determined in normal rats and those exposed to influence of chronic stress during gestation. Data were registered six months after the birth and in 5, 24 and 48 hours after their immobilization. Analysis of the data showed that in rats undergoing stress, recorded systolic, diastolic blood pressure and heart rate both before and during all periods of immobilization were significantly below than in control group. It is concluded that the maximum limit of motor activity in the prenatally stressed rats accompanied by a decrease in the values recorded performance of the cardiovascular system, which is reflecting the decrease in these animals reactivity of the cardiovascular system, and thus the adaptive capacity for action of stress factors. PMID- 26355323 TI - Elimination of Ebola Virus Transmission in Liberia - September 3, 2015. AB - Following 42 days since the last Ebola virus disease (Ebola) patient was discharged from a Liberian Ebola treatment unit (ETU), September 3, 2015, marks the second time in a 4-month period that the World Health Organization (WHO) has declared Liberia free of Ebola virus transmission (1). The first confirmed Ebola cases in West Africa were identified in southeastern Guinea on March 23, 2014, and within 1 week, cases were identified and confirmed in Liberia (1). Since then, Liberia has reported 5,036 confirmed and probable Ebola cases and 4,808 Ebola-related deaths. The epidemic in Liberia peaked in late summer and early fall of 2014, when more than 200 confirmed and probable cases were reported each week . PMID- 26355324 TI - Efficacy of Multiple Micronutrients Fortified Milk Consumption on Iron Nutritional Status in Moroccan Schoolchildren. AB - Iron deficiency constitutes a major public health problem in Morocco, mainly among women and children. The aim of our paper is to assess the efficacy of consumption of multiple micronutrients (MMN) fortified milk on iron status of Moroccan schoolchildren living in rural region. Children (N = 195), aged 7 to 9 y, were recruited from schools and divided into two groups: the nonfortified group (NFG) received daily a nonfortified Ultra-High-Temperature (UHT) milk and the fortified group received (FG) daily UHT milk fortified with multiple micronutrients including iron sulfate. Blood samples were collected at baseline (T0) and after 9 months (T9). Hemoglobin (Hb) was measured in situ by Hemocue device; ferritin and C Reactive Protein were assessed in serum using ELISA and nephelometry techniques, respectively. Results were considered significant when the p value was <0.05. At T9 FG showed a reduction of iron deficiency from 50.9% to 37.2% (p = 0.037). Despite the low prevalence of iron deficiency anemia (1.9%); more than 50% of children in our sample suffered from iron deficiency at baseline. The consumption of fortified milk reduced the prevalence of iron deficiency by 27% in schoolchildren living in high altitude rural region of Morocco. Clinical Trial Registration. Our study is registered in the Pan African Clinical Trial Registry with the identification number PACTR201410000896410. PMID- 26355325 TI - Efficacy of stepwise application of orthosis and kinesiology tape for treating thumb metacarpophalangeal joint hyperextension injury. AB - [Purpose] The purpose of this study was to investigate on the effects of the stepwise application of orthosis and kinesiology tape on a patient with thumb metacarpophalangeal joint hyperextension injury. [Subject] The patient was a 43 year-old man with severe thumb MCP pain and extremely limited thumb movement. [Methods] Stepwise application of orthosis and kinesiology taping were performed for 3 weeks and 4 weeks, respectively. [Results] After stepwise treatment, the patient was able to power grip, precision pinch, turn a key, and hold a pen without pain. [Conclusion] Stepwise application of thumb orthosis and kinesiology tape is a safe and effective treatment for thumb MCP joint hyperextension injury. PMID- 26355326 TI - Update on Hepatitis B Virus Infection: Focus on Treatment. AB - This review article is an update of the current treatment strategies available for chronic hepatitis B. In addition to achieving on-therapy clinical remission and suppression of HBV replication without resistance, the ultimate goal of therapy is the development of sustained remission and HBsAg loss after discontinuation of treatment. This is the closest possible to cure outcome for hepatitis B virus (HBV) infection. These goals can be achieved by response-guided courses of pegylated interferon (peg-IFN)-alpha at rates higher than 30%, both in hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients. Review of the data regarding discontinuation of long term NA treatment in HBeAg-negative patients revealed that stopping such therapy is safe with high rates of sustained off treatment responses that appear to be immunologically induced. Decreasing hepatitis B surface antigen (HBsAg) titers under therapy to <500, particularly <100 IU/mL, and adding a course of peg-IFN to ongoing long term nucleos(t)ide analogue (NA) therapy increase the percentage of sustained responses following discontinuation of NA treatment. PMID- 26355328 TI - Animated Depth Images for Interactive Remote Visualization of Time-Varying Data Sets. AB - Remote visualization has become both a necessity, as data set sizes have grown faster than computer network performance, and an opportunity, as laptop, tablet, and smartphone mobile computing platforms have become ubiquitous. However, the conventional remote visualization (CRV) approach of sending a new image from the server to the client for every view parameter change suffers from reduced interactivity. One problem is high latency, as the network has to be traversed twice, once to communicate the view parameters to the server and once to transmit the new image to the client. A second problem is reduced image quality due to aggressive compression or low resolution. We address these problems by constructing and transmitting enhanced images that are sufficient for quality output frame reconstruction at the client for a range of view parameter values. The client reconstructs thousands of frames locally, without any additional data from the server, which avoids latency and aggressive compression. We introduce animated depth images, which not only store a color and depth sample at every pixel, but also store the trajectory of the samples for a given time interval. Sample trajectories are stored compactly by partitioning the image into semi rigid sample clusters and by storing one sequence of rigid body transformations per cluster. Animated depth images leverage sample trajectory coherence to achieve a good compression of animation data, with a small and user-controllable approximation error. We demonstrate animated depth images in the context of finite element analysis and SPH data sets. PMID- 26355327 TI - Colon adenocarcinoma with dome-like phenotype: characteristic endoscopic ultrasonography (EUS) findings. AB - An 80-year-old man underwent colonoscopy for proctorrhagia. Conventional white light imaging showed a superficially flat and elevated lesion that appeared to be a submucosal tumor of the sigmoid colon. Chromoendoscopy with Indigo Carmine showed that the margin of the tumor was covered with normal epithelium but that there was a slight depression on its surface. Magnification endoscopy with Crystal Violet staining revealed the amorphous surface structure of the depressed lesion, but the surrounding mucosa showed a normal pit pattern. Endoscopic ultrasonography demonstrated that a hypoechoic mass was located in the submucosal layer, and a biopsy specimen obtained from the surface of the lesion showed evidence of adenocarcinoma. We then performed sigmoidectomy on the patient. Immunohistochemically, the tumor cells were positive for two mismatch repair proteins (MLH1 and MSH2), but in situ hybridization revealed that the specimen was negative for the Epstein - Barr virus. We finally diagnosed the lesion as adenocarcinoma with a dome-like phenotype of the sigmoid colon. PMID- 26355329 TI - Detection and Reconstruction of an Implicit Boundary Surface by Adaptively Expanding A Small Surface Patch in a 3D Image. AB - In this paper we propose a novel and easy to use 3D reconstruction method. With the method, users only need to specify a small boundary surface patch in a 2D section image, and then an entire continuous implicit boundary surface (CIBS) can be automatically reconstructed from a 3D image. In the method, a hierarchical tracing strategy is used to grow the known boundary surface patch gradually in the 3D image. An adaptive detection technique is applied to detect boundary surface patches from different local regions. The technique is based on both context dependence and adaptive contrast detection as in the human vision system. A recognition technique is used to distinguish true boundary surface patches from the false ones in different cubes. By integrating these different approaches, a high-resolution CIBS model can be automatically reconstructed by adaptively expanding the small boundary surface patch in the 3D image. The effectiveness of our method is demonstrated by its applications to a variety of real 3D images, where the CIBS with complex shapes/branches and with varying gray values/gradient magnitudes can be well reconstructed. Our method is easy to use, which provides a valuable tool for 3D image visualization and analysis as needed in many applications. PMID- 26355330 TI - Filling Your Shelves: Synthesizing Diverse Style-Preserving Artifact Arrangements. AB - Our homes and workspaces are filled with collections of dozens of artifacts laid out on surfaces such as shelves, counters, and mantles. The content and layout of these arrangements reflect both context, e.g., kitchen or living room, and style, e.g., neat or messy. Manually assembling such arrangements in virtual scenes is highly time consuming, especially when one needs to generate multiple diverse arrangements for numerous support surfaces and living spaces. We present a data driven method especially designed for artifact arrangement which automatically populates empty surfaces with diverse believable arrangements of artifacts in a given style. The input to our method is an annotated photograph or a 3D model of an exemplar arrangement, that reflects the desired context and style. Our method leverages this exemplar to generate diverse arrangements reflecting the exemplar style for arbitrary furniture setups and layout dimensions. To simultaneously achieve scalability, diversity and style preservation, we define a valid solution space of arrangements that reflect the input style. We obtain solutions within this space using barrier functions and stochastic optimization. PMID- 26355331 TI - Generating Facial Expressions Using an Anatomically Accurate Biomechanical Model. AB - This paper presents a computational framework for modelling the biomechanics of human facial expressions. A detailed high-order (Cubic-Hermite) finite element model of the human head was constructed using anatomical data segmented from magnetic resonance images. The model includes a superficial soft-tissue continuum consisting of skin, the subcutaneous layer and the superficial Musculo Aponeurotic system. Embedded within this continuum mesh, are 20 pairs of facial muscles which drive facial expressions. These muscles were treated as transversely-isotropic and their anatomical geometries and fibre orientations were accurately depicted. In order to capture the relative composition of muscles and fat, material heterogeneity was also introduced into the model. Complex contact interactions between the lips, eyelids, and between superficial soft tissue continuum and deep rigid skeletal bones were also computed. In addition, this paper investigates the impact of incorporating material heterogeneity and contact interactions, which are often neglected in similar studies. Four facial expressions were simulated using the developed model and the results were compared with surface data obtained from a 3D structured-light scanner. Predicted expressions showed good agreement with the experimental data. PMID- 26355332 TI - How to Display Group Information on Node-Link Diagrams: An Evaluation. AB - We present the results of evaluating four techniques for displaying group or cluster information overlaid on node-link diagrams: node coloring, GMap, BubbleSets, and LineSets. The contributions of the paper are three fold. First, we present quantitative results and statistical analyses of data from an online study in which approximately 800 subjects performed 10 types of group and network tasks in the four evaluated visualizations. Specifically, we show that BubbleSets is the best alternative for tasks involving group membership assessment; that visually encoding group information over basic node-link diagrams incurs an accuracy penalty of about 25 percent in solving network tasks; and that GMap's use of prominent group labels improves memorability. We also show that GMap's visual metaphor can be slightly altered to outperform BubbleSets in group membership assessment. Second, we discuss visual characteristics that can explain the observed quantitative differences in the four visualizations and suggest design recommendations. This discussion is supported by a small scale eye tracking study and previous results from the visualization literature. Third, we present an easily extensible user study methodology. PMID- 26355333 TI - Perceptually Uniform Motion Space. AB - Flow data is often visualized by animated particles inserted into a flow field. The velocity of a particle on the screen is typically linearly scaled by the velocities in the data. However, the perception of velocity magnitude in animated particles is not necessarily linear. We present a study on how different parameters affect relative motion perception. We have investigated the impact of four parameters. The parameters consist of speed multiplier, direction, contrast type and the global velocity scale. In addition, we investigated if multiple motion cues, and point distribution, affect the speed estimation. Several studies were executed to investigate the impact of each parameter. In the initial results, we noticed trends in scale and multiplier. Using the trends for the significant parameters, we designed a compensation model, which adjusts the particle speed to compensate for the effect of the parameters. We then performed a second study to investigate the performance of the compensation model. From the second study we detected a constant estimation error, which we adjusted for in the last study. In addition, we connect our work to established theories in psychophysics by comparing our model to a model based on Stevens' Power Law. PMID- 26355334 TI - Study of a Ray Casting Technique for the Visualization of Deformable Volumes. AB - Deformable models are widely used in many disciplines such as engineering and medicine. Real objects are usually scanned to create models in such applications. In many cases the shape of the object is extracted from volumetric data acquired during the scanning phase. At the same time, this volume can be used to define the model's appearance. In order to achieve a visualization that unifies the shape (physical model) and appearance (scanned volume) specially adapted volume rendering techniques are required. One of the most common volumetric visualization techniques is ray casting, which also enables the use of different corrections or improvements such as adaptive sampling or stochastic jittering. This paper presents an extensive study about a ray casting method for tetrahedral meshes with an underlying structured volume. This allows a direct visualization of the deformed model without losing the information contained in the volume. The aim of this study is to analyse and compare the different methods for ray traversal and illumination correction, resulting in a comprehensive relation of the different methods, their computational cost and visual performance. PMID- 26355335 TI - The Natural Helmholtz-Hodge Decomposition for Open-Boundary Flow Analysis. AB - The Helmholtz-Hodge decomposition (HHD), which describes a flow as the sum of an incompressible, an irrotational, and a harmonic flow, is a fundamental tool for simulation and analysis. Unfortunately, for bounded domains, the HHD is not uniquely defined, traditionally, boundary conditions are imposed to obtain a unique solution. However, in general, the boundary conditions used during the simulation may not be known known, or the simulation may use open boundary conditions. In these cases, the flow imposed by traditional boundary conditions may not be compatible with the given data, which leads to sometimes drastic artifacts and distortions in all three components, hence producing unphysical results. This paper proposes the natural HHD, which is defined by separating the flow into internal and external components. Using a completely data-driven approach, the proposed technique obtains uniqueness without assuming boundary conditions a priori. As a result, it enables a reliable and artifact-free analysis for flows with open boundaries or unknown boundary conditions. Furthermore, our approach computes the HHD on a point-wise basis in contrast to the existing global techniques, and thus supports computing inexpensive local approximations for any subset of the domain. Finally, the technique is easy to implement for a variety of spatial discretizations and interpolated fields in both two and three dimensions. PMID- 26355336 TI - Unbiased Sampling and Meshing of Isosurfaces. AB - In this paper, we present a new technique to generate unbiased samples on isosurfaces. An isosurface, F(x; y; z) = c, of a function, F, is implicitly defined by trilinear interpolation of background grid points. The key idea of our approach is that of treating the isosurface within a grid cell as a graph (height) function in one of the three coordinate axis directions, restricted to where the slope is not too high, and integrating / sampling from each of these three. We use this unbiased sampling algorithm for applications in Monte Carlo integration, Poisson-disk sampling, and isosurface meshing. PMID- 26355337 TI - Visual Adjacency Lists for Dynamic Graphs. AB - We present a visual representation for dynamic, weighted graphs based on the concept of adjacency lists. Two orthogonal axes are used: one for all nodes of the displayed graph, the other for the corresponding links. Colors and labels are employed to identify the nodes. The usage of color allows us to scale the visualization to single pixel level for large graphs. In contrast to other techniques, we employ an asymmetric mapping that results in an aligned and compact representation of links. Our approach is independent of the specific properties of the graph to be visualized, but certain graphs and tasks benefit from the asymmetry. As we show in our results, the strength of our technique is the visualization of dynamic graphs. In particular, sparse graphs benefit from the compact representation. Furthermore, our approach uses visual encoding by size to represent weights and therefore allows easy quantification and comparison. We evaluate our approach in a quantitative user study that confirms the suitability for dynamic and weighted graphs. Finally, we demonstrate our approach for two examples of dynamic graphs. PMID- 26355338 TI - Transcriptional and posttranscriptional regulation of Bacillus sp. CDB3 arsenic resistance operon ars1. AB - Bacillus sp. CDB3 possesses a novel eight-gene ars cluster (ars1, arsRYCDATorf7orf8) with some unusual features in regard to expression regulation. This study demonstrated that the cluster is a single operon but can also produce a short three-gene arsRYC transcript. A hairpin structure formed by internal inverted repeats between arsC and arsD was shown to diminish the expression of the full operon, thereby probably acting as a transcription attenuator. A degradation product of the arsRYC transcript was also identified. Electrophoretic mobility shift analysis demonstrated that ArsR interacts with the ars1 promoter forming a protein-DNA complex that could be impaired by arsenite. However, no interaction was detected between ArsD and the ars1 promoter, suggesting that the CDB3 ArsD protein may not play a regulatory role. Compared to other ars gene clusters, regulation of the Bacillus sp. CDB3 ars1 operon is more complex. It represents another example of specific mRNA degradation in the transporter gene region and possibly the first case of attenuator-mediated regulation of ars operons. PMID- 26355339 TI - Found in Translation. PMID- 26355340 TI - Graphene-Wrapped Anatase TiO2 Nanofibers as High-Rate and Long-Cycle-Life Anode Material for Sodium Ion Batteries. AB - Anatase TiO2 has been suggested as a potential sodium anode material, but the low electrical conductivity of TiO2 often limits the rate capability, resulting in poor electrochemical properties. To address this limitation, we propose graphene wrapped anatase TiO2 nanofibers (rGO@TiO2 NFs) through an effective wrapping of reduced graphene oxide (rGO) sheets on electrospun TiO2 NFs. To provide strong electrostatic interaction between the graphene oxide (GO) sheets and the TiO2 NFs, poly(allylamine hydrochloride) (PAH) was used to induce a positively charged TiO2 surface by the immobilization of the -NH3(+) group and to promote bonding with the negatively charged carboxylic acid (-COO(-)) and hydroxyl (-O(-)) groups on the GO. A sodium anode electrode using rGO@TiO2 NFs exhibited a significantly improved initial capacity of 217 mAh g(-1), high capacity retention (85% after 200 cycles at 0.2C), and a high average Coulombic efficiency (99.7% from the second cycle to the 200th cycle), even at a 5C rate, compared to those of pristine TiO2 NFs. The improved electrochemical performances stem from highly conductive properties of the reduced GO which is effectively anchored to the TiO2 NFs. PMID- 26355341 TI - Towards a science of eating disorders: Replacing myths with realities: The fourth Birgit Olsson lecture. AB - BACKGROUND: For too long we have been "stuck" in old perspectives that have hampered the advance of knowledge. In part, this is related to the challenges that people have in unlearning misinformation. AIM: To address the need for an upgrade in the eating disorders field. METHOD: To assist with replacing outdated and inaccurate ideas with new data, this lecture reviewed novel approaches to eating disorders that engage scientists and clinicians from diverse fields to approach questions about aetiology and treatment of eating disorders through new lenses. This forward-looking lecture outlined critical questions that need to be addressed to move the field forward and strategies for engaging scientists from different fields. RESULTS: Leading-edge findings on genetics, intestinal microbiota, and neuroscience are reviewed. CONCLUSIONS: This review encourages the integration of new evidence-based knowledge to form the backbone of our understanding of and approach to eating disorders. PMID- 26355342 TI - ER stress induces NLRP3 inflammasome activation and hepatocyte death. AB - The incidence of chronic liver disease is constantly increasing, owing to the obesity epidemic. However, the causes and mechanisms of inflammation-mediated liver damage remain poorly understood. Endoplasmic reticulum (ER) stress is an initiator of cell death and inflammatory mechanisms. Although obesity induces ER stress, the interplay between hepatic ER stress, NLRP3 inflammasome activation and hepatocyte death signaling has not yet been explored during the etiology of chronic liver diseases. Steatosis is a common disorder affecting obese patients; moreover, 25% of these patients develop steatohepatitis with an inherent risk for progression to hepatocarcinoma. Increased plasma LPS levels have been detected in the serum of patients with steatohepatitis. We hypothesized that, as a consequence of increased plasma LPS, ER stress could be induced and lead to NLRP3 inflammasome activation and hepatocyte death associated with steatohepatitis progression. In livers from obese mice, administration of LPS or tunicamycin results in IRE1alpha and PERK activation, leading to the overexpression of CHOP. This, in turn, activates the NLRP3 inflammasome, subsequently initiating hepatocyte pyroptosis (caspase-1, -11, interleukin-1beta secretion) and apoptosis (caspase-3, BH3-only proteins). In contrast, the LPS challenge is blocked by the ER stress inhibitor TUDCA, resulting in: CHOP downregulation, reduced caspase-1, caspase-11, caspase-3 activities, lowered interleukin-1beta secretion and rescue from cell death. The central role of CHOP in mediating the activation of proinflammatory caspases and cell death was characterized by performing knockdown experiments in primary mouse hepatocytes. Finally, the analysis of human steatohepatitis liver biopsies showed a correlation between the upregulation of inflammasome and ER stress markers, as well as liver injury. We demonstrate here that ER stress leads to hepatic NLRP3 inflammasome pyroptotic death, thus contributing as a novel mechanism of inflammation-mediated liver injury in chronic liver diseases. Inhibition of ER-dependent inflammasome activation and cell death pathways may represent a potential therapeutic approach in chronic liver diseases. PMID- 26355343 TI - Autophagy regulates hepatocyte identity and epithelial-to-mesenchymal and mesenchymal-to-epithelial transitions promoting Snail degradation. AB - Epithelial-to-mesenchymal transition (EMT) and the reverse process mesenchymal-to epithelial transition (MET) are events involved in development, wound healing and stem cell behaviour and contribute pathologically to cancer progression. The identification of the molecular mechanisms underlying these phenotypic conversions in hepatocytes are fundamental to design specific therapeutic strategies aimed at optimising liver repair. The role of autophagy in EMT/MET processes of hepatocytes was investigated in liver-specific autophagy-deficient mice (Alb-Cre;ATG7(fl/fl)) and using the nontumorigenic immortalised hepatocytes cell line MMH. Autophagy deficiency in vivo reduces epithelial markers' expression and increases the levels of mesenchymal markers. These alterations are associated with an increased protein level of the EMT master regulator Snail, without transcriptional induction. Interestingly, we found that autophagy degrades Snail in a p62/SQSTM1 (Sequestosome-1)-dependent manner. Moreover, accordingly to a pro-epithelial function, we observed that autophagy stimulation strongly affects EMT progression, whereas it is necessary for MET. Finally, we found that the EMT induced by TGFbeta affects the autophagy flux, indicating that these processes regulate each other. Overall, we found that autophagy regulates the phenotype plasticity of hepatocytes promoting their epithelial identity through the inhibition of the mesenchymal programme. PMID- 26355344 TI - A cascade of protein aggregation bombards mitochondria for neurodegeneration and apoptosis under WWOX deficiency. PMID- 26355345 TI - Preventing ototoxic hearing loss by inhibiting histone deacetylases. PMID- 26355346 TI - Radiation-induced gamma-synuclein in regards to DC function. PMID- 26355348 TI - High-Efficiency Small Molecule-Based Bulk-Heterojunction Solar Cells Enhanced by Additive Annealing. AB - Solvent additive processing is important in optimizing an active layer's morphology and thus improving the performance of organic solar cells (OSCs). In this study, we find that how 1,8-diiodooctane (DIO) additive is removed plays a critical role in determining the film morphology of the bulk heterojunction OSCs in inverted structure based on a porphyrin small molecule. Different from the cases reported for polymer-based OSCs in conventional structures, the inverted OSCs upon the quick removal of the additive either by quick vacuuming or methanol washing exhibit poorer performance. In contrast, the devices after keeping the active layers in ambient pressure with additive dwelling for about 1 h (namely, additive annealing) show an enhanced power conversion efficiency up to 7.78% with a large short circuit current of 19.25 mA/cm(2), which are among the best in small molecule-based solar cells. The detailed morphology analyses using UV-vis absorption spectroscopy, grazing incidence X-ray diffraction, resonant soft X-ray scattering, and atomic force microscopy demonstrate that the active layer shows smaller-sized phase separation but improved structure order upon additive annealing. On the contrary, the quick removal of the additive either by quick vacuuming or methanol washing keeps the active layers in an earlier stage of large scaled phase separation. PMID- 26355347 TI - Absence of RIPK3 predicts necroptosis resistance in malignant melanoma. AB - Acquired or intrinsic resistance to apoptotic and necroptotic stimuli is considered a major hindrance of therapeutic success in malignant melanoma. Inhibitor of apoptosis proteins (IAPs) are important regulators of apoptotic and necroptotic cell death mediated by numerous cell death signalling platforms. In this report we investigated the impact of IAPs for cell death regulation in malignant melanoma. Suppression of IAPs strongly sensitized a panel of melanoma cells to death ligand-induced cell death, which, surprisingly, was largely mediated by apoptosis, as it was completely rescued by addition of caspase inhibitors. Interestingly, the absence of necroptosis signalling correlated with a lack of receptor-interacting protein kinase-3 (RIPK3) mRNA and protein expression in all cell lines, whereas primary melanocytes and cultured nevus cells strongly expressed RIPK3. Reconstitution of RIPK3, but not a RIPK3-kinase dead mutant in a set of melanoma cell lines overcame CD95L/IAP antagonist-induced necroptosis resistance independent of autocrine tumour necrosis factor secretion. Using specific inhibitors, functional studies revealed that RIPK3-mediated mixed lineage kinase domain-like protein (MLKL) phosphorylation and necroptosis induction critically required receptor-interacting protein kinase-1 signalling. Furthermore, the inhibitor of mutant BRAF Dabrafenib, but not Vemurafenib, inhibited necroptosis in melanoma cells whenever RIPK3 is present. Our data suggest that loss of RIPK3 in melanoma and selective inhibition of the RIPK3/MLKL axis by BRAF inhibitor Dabrafenib, but not Vemurafenib, is critical to protect from necroptosis. Strategies that allow RIPK3 expression may allow unmasking the necroptotic signalling machinery in melanoma and points to reactivation of this pathway as a treatment option for metastatic melanoma. PMID- 26355349 TI - Formation of bilayer membrane and niosomes by double-tailed polyglyceryl-type nonionic surfactant. AB - Vesicles with synthetic nonionic surfactants are called niosomes or NSVs, and these have been the focus of attention as an alternative to phospholipid liposomes as drug carriers. Especially it is demanded to discover novel niosomal systems with polyol-type nonionic surfactants from the viewpoint of environmental aspects. In this paper, a novel series of double-tailed nonionic surfactants, polyglyceryl dialkyl ethers, (C12)2Gn (n = 2.3, 5.4, 9.4, and 13.8), was synthesized, and its aqueous phase behavior and niosome formation were studied. Because of its double-tailed molecular structure, a lamellar liquid crystalline phase was dominant in the binary phase diagrams for different polyglyceryl chain lengths. The single lamellar liquid crystalline phase region was expanded as the polymerization degree in the hydrophilic moiety increased. Small-angle X-ray scattering spectra revealed the lamellar structure for the (C12)2G2.3 was extremely loose. Molecular packing in the lamellar phase was analyzed except for the (C12)2G2.3 system by using a geometrical model of the lamellar phase. The effective cross-sectional area per molecule at the interface increased extensively as dilution for the (C12)2G13.8 system but remained almost unchanged for the (C12)2G5.4 system. From the molecular parameters, water-holding ability in the lamellar phase was evaluated, and the results indicated strong hydration ability of the long polyglyceryl chain. In a dilute region, micron-sized giant niosomes and small niosomes of about 100 nm were formulated by vortex mixing and ultrasonication, respectively. The multilamellar structure of the small niosomes was confirmed by transmission electron microscopy. Cholesterol addition in the present surfactant lamellar phase induced the phase transition to the liquid ordered phase, which is the same phenomenon in a phospholipid-cholesterol mixture. The stability of niosomes with/without cholesterol was monitored by the niosome size change. In both cases, the niosomes were stable for at least 100 days. PMID- 26355350 TI - Perforated Metal Oxide-Carbon Nanotube Composite Microspheres with Enhanced Lithium-Ion Storage Properties. AB - Metal oxide-carbon nanotube (CNT) composite microspheres with a novel structure were fabricated using a one-step spray pyrolysis process. Metal oxide-CNT composite microspheres with a uniform distribution of void nanospheres were prepared from a colloidal spray solution containing CNTs, metal salts, and polystyrene (PS) nanobeads. Perforated SnO2-CNT composite microspheres with a uniform distribution of void nanospheres showed excellent lithium storage properties as anode materials for lithium-ion batteries. Bare SnO2 microspheres and SnO2-CNT composite microspheres with perforated and filled structures had a discharge capacity of 450, 1108, and 590 mA h g(-1) for the 250th cycle at a current density of 1.5 A g(-1), and the corresponding capacity retention compared to the second cycle was 41, 98, and 55%, respectively. The synergetic combination of void nanospheres and flexible CNTs improved the electrochemical properties of SnO2. This effective and innovative strategy could be used for the preparation of perforated metal oxide-CNT composites with complex elemental compositions for many applications. PMID- 26355351 TI - Direct One-Pot Synthesis of Nucleosides from Unprotected or 5-O-Monoprotected D Ribose. AB - New, improved methods to access nucleosides are of general interest not only to organic chemists but to the greater scientific community as a whole due their key implications in life and disease. Current synthetic methods involve multistep procedures employing protected sugars in the glycosylation of nucleobases. Using modified Mitsunobu conditions, we report on the first direct glycosylation of purine and pyrimidine nucleobases with unprotected D-ribose to provide beta pyranosyl nucleosides and a one-pot strategy to yield beta-furanosides from the heterocycle and 5-O-monoprotected D-ribose. PMID- 26355352 TI - Cationic Copolymerization of 3,3-Bis(hydroxymethyl)oxetane and Glycidol: Biocompatible Hyperbranched Polyether Polyols with High Content of Primary Hydroxyl Groups. AB - The cationic ring-opening copolymerization of 3,3-bis(hydroxymethyl)oxetane (BHMO) with glycidol using different comonomer ratios (BHMO content from 25 to 90%) and BF3OEt2 as an initiator has been studied. Apparent molecular weights of the resulting hyperbranched polyether copolymers ranged from 1400 to 3300 g mol( 1) (PDI: 1.21-1.48; method: SEC, linear PEG standards). Incorporation of both comonomers is evidenced by MALDI-TOF mass spectroscopy. All hyperbranched polyether polyols with high content of primary hydroxyl groups portray good solubility in water, which correlates with an increasing content of glycerol units. Detailed NMR characterization was employed to elucidate the copolymer microstructures. Kinetic studies via FTIR demonstrated a weak gradient-type character of the copolymers. MTT assays of the copolymers (up to 100 MUg mL(-1)) on HEK and fibroblast cell lines (3T3, L929, WEHI) as well as viability tests on the fibroblast cells were carried out to assess the biocompatibility of the materials, confirming excellent biocompatibility. Transfection efficiency characterization by flow cytometry and confocal laser microscopy demonstrated cellular uptake of the copolymers. Antiadhesive properties of the materials on surfaces were assessed by adhesion assays with fibroblast cells. PMID- 26355353 TI - Split data by gender to improve service provision. PMID- 26355354 TI - New immigration rules: the impact on the workforce. PMID- 26355355 TI - Attitudes of nursing staff towards a Modified Early Warning System. AB - This study aimed to understand the attitudes of qualified nursing staff on an acute medical unit concerning the Modified Early Warning System (MEWS) score chart used to monitor patients. A combination of questionnaires and a focus group was used. All respondents believed that the MEWS is beneficial in their work but the point was also raised that MEWS scores can be miscalculated and there is sometimes difficulty in getting medical staff to review the patient, even if the MEWS score is significantly high. At times a qualified nurse's seniority or the colour of his or her uniform can affect the attitude of the medical staff and can mean the difference between the patient being reviewed or not. Certain medics have a culture of dismissing a high MEWS score because they were expecting these vital physiological signs to be abnormal, owing to that particular patient's past medical history or presenting complaint. Most hospitals in the NHS now use some sort of early warning system but, at times, staff seem to be unsure of the importance of the MEWS score or what action needs to be taken. The authors agree with the view that introduction of a standard NHS-wide chart would be of benefit to staff and patients. PMID- 26355356 TI - Emergency care within hospitals: can it be done more efficiently? AB - INTRODUCTION: Cardiac Arrest Teams (CATs) are frequently activated by nurses when patients experience 'false arrests' (FAs). In those cases activation of the Rapid Response Team (RRT) might be more efficient. The authors determined the level of urgency of FAs to find a scope for improvement in efficiency within emergency care. METHODS: CAT-activations for FAs in a university hospital from September 2009 to 2012 were retrospectively analysed and classified as urgent or less urgent. RESULTS: In 26% (107/405) the CAT was activated for FAs. Calls were classified as urgent in 43% (46/107). Less urgent calls comprised 57% (61/107) of the FAs, difference 14% (95%CI: 1% to 26%). CONCLUSIONS: A significant part of the CAT-activations for FAs were less urgent and an RRT-activation might be more efficient. To minimise the CAT-activations for FAs, nurses need to recognise early patients who clinically deteriorate. Therefore, nurses should use the Modified Early Warning Score correctly. PMID- 26355357 TI - A final reflection on my time as a nursing student. AB - In his final Student Column, Ed Freshwater looks back over the 3 years of his degree considering the things that went well, and the things he might have done differently. PMID- 26355358 TI - Empowering patients with diabetes. AB - Maggie Meer, founder of this November's Diabetes Professional Care event and long standing diabetes patient, gives her views on how nurses can capitalise on their pivotal role to empower patients with diabetes and improve self-management. PMID- 26355359 TI - Posters as assessment strategies: focusing on service users. AB - This article debates whether posters as an assessment strategy in health professionals' education programmes can benefit learners, academics, and service users. Evidence suggests that service-user involvement benefits learning by developing students' communication, partnership and advocacy skills. The authors debate the value of posters as an assessment strategy in postgraduate diploma nursing programmes delivered in an Irish School of Nursing, Midwifery and Health Systems. It is argued that assessment strategies should not only examine programme theory and practice but should also benefit the people that will be using the service. Although the assessment strategy used in these programmes aimed to benefit service users, additional work is required for assessment to be truly inclusive of service users. PMID- 26355360 TI - Delivering compassionate care: the enablers and barriers. AB - The importance of providing compassionate care to patients is well established. While compassionate care can be understood as an individual response to others' vulnerability, it is acknowledged that healthcare environments can impact significantly on this aspect of practice. This study sought to explore how health professionals and pre-qualifying healthcare students (HCS) understand compassionate care and factors that hinder or enable them to practice compassionately. The perceptions of health professionals (n=146) and HCS (n=166) registered at a university in Northwest England were explored using mixed methods. This article reports on the data gained from the qualitative interviews and responses to open-text questions from the mainly quantitative questionnaire. The findings are discussed under the following themes: individual and relationship factors that impact on compassionate care practice; organisational factors that impact on the clinical environment and team; and leadership factors that hinder or enable a compassionate care culture. This article argues that there are a number of enabling factors that enhance a culture conducive to providing compassionate care. These include leaders who act as positive role models, good relationships between team members and a focus on staff wellbeing. PMID- 26355361 TI - The Government's plan for ensuring compassionate care in the NHS. AB - In this first of a two-part column, John Tingle discusses the recent speech given by Secretary of State for Health, Jeremy Hunt, at the King's Fund, on making health care more human-centered, not system-centered. PMID- 26355362 TI - The professional duty of candour. AB - Emeritus professor Alan Glasper, of the University of Southampton discusses the recently published report looking at the duty of health professionals to be open and honest with patients and people close to them. PMID- 26355363 TI - Relationships: from staff nurse to nurse consultant. PMID- 26355364 TI - Preparing to embrace revalidation. PMID- 26355366 TI - Pigmented Lesions of the Nervous System and the Neural Crest: Lessons From Embryology. AB - Neurosurgeons encounter a number of pigmented tumors of the central nervous system in a variety of locations, including primary central nervous system melanoma, blue nevus of the spinal cord, and melanotic schwannoma. When examined through the lens of embryology, pigmented lesions share a unifying connection: They occur in structures that are neural crest cell derivatives. Here, we review the important progress made in the embryology of neural crest cells, present 3 cases of pigmented tumors of the nervous system, and discuss these clinical entities in the context of the development of melanoblasts. Pigmented lesions of the nervous system arise along neural crest cell migration routes and from neural crest-derived precursors. Awareness of the evolutionary clues of vertebrate pigmentation by the neurosurgical and neuro-oncological community at large is valuable for identifying pathogenic or therapeutic targets and for designing future research on nervous system pigmented lesions. When encountering such a lesion, clinicians should be aware of the embryological basis to direct additional evaluation, including genetic testing, and to work with the scientific community in better understanding these lesions and their relationship to neural crest developmental biology. PMID- 26355368 TI - Mercury Measurement and Its Control: What We Know, Have Learned, and Need to Further Investigate. AB - Based on the available evidence of health effects, the U.S. Environmental Protection Agency (EPA) has been evaluating the need to regulate mercury releases to the environment. In response to the congressional mandates in The 1990 Clean Air Act Amendments (CAAA), the EPA has issued the Mercury Study Report and the Study of Hazardous Air Pollutant Emissions from Electric Utility Steam Generating Units Report. In spite of the enormous effort represented by these reports, as well as the efforts of both the U.S. Department of Energy (DOE) and the Electric Power Research Institute (EPRI), in conducting the field measurement programs that form the basis for these reports, a definitive answer on the need for mercury regulation has not been found. However, the EPA, as well as other regulatory agencies and health researchers, have suggested a "plausible link" between anthropogenic sources emitting mercury and the methylation, bioaccumulation in the food chain, and adverse health effects in humans and wildlife. PMID- 26355365 TI - Unravelling New Processes at Interfaces: Photochemical Isoprene Production at the Sea Surface. AB - Isoprene is an important reactive gas that is produced mainly in terrestrial ecosystems but is also produced in marine ecosystems. In the marine environment, isoprene is produced in the seawater by various biological processes. Here, we show that photosensitized reactions involving the sea-surface microlayer lead to the production of significant amounts of isoprene. It is suggested that H abstraction processes are initiated by photochemically excited dissolved organic matter which will the degrade fatty acids acting as surfactants. This chemical interfacial processing may represent a significant abiotic source of isoprene in the marine boundary layer. PMID- 26355369 TI - Mercury Measurement and Its Control: What We Know, Have Learned, and Need to Further Investigate. AB - The U.S. Department of Energy (DOE), through the Federal Energy Technology Center (FETC), manages the largest funded program in the country for developing (1) an understanding of mercury emissions, (2) measurement of these emissions, and (3) control technology (-ies) for these emissions for the U.S. coal-fired electric generating industry. DOE has initiated, or has collaborated with other government and industrial organizations in, these and other efforts relating to mercury and other hazardous air pollutants (HAPs), also known as air toxics. One of DOE's first reports on trace elements in coal was conducted from 1976 through 1978 by researchers at DOE's Pittsburgh Energy Technology Center (PETC, now FETC) and the Pittsburgh Mining Operations of the Department of the Interior's Bureau of Mines. The report was completed less than two years after DOE was formed, and 13 years before Title III of the 1990 Clean Air Act Amendments was enacted (Cavallaro et al., March 1978). PMID- 26355370 TI - Middle- and Neighborhood-Scale Variations of PM10 Source Contributions in Las Vegas, Nevada. AB - The Las Vegas Valley PM10 Study was conducted during 1995 to determine the contributions to PM10 aerosol from fugitive dust, motor vehicle exhaust, residential wood combustion, and secondary aerosol sources. Twenty-four-hr PM10 samples were collected at two neighborhood-scale sites every sixth day for 13 months. Five week-long intensive studies were conducted over a middle-scale sub region at 29 locations that contained many construction projects emitting fugitive dust. The study found that the zone of influence around individual emitters was less than 1 km. Most of the sampling sites in residential and commercial areas yielded equivalent PM10 concentrations in the neighborhood region, even though they were more distant from each other than they were from the nearby construction sources. Based on chemical mass balance (CMB) receptor modeling, fugitive dust accounted for 80-90% of the PM10, and motor vehicle exhaust accounted for 3-9% of the PM10 in the Las Vegas Valley. PMID- 26355371 TI - Estimates of Sulfate Deposition in the Middle Eastern United States: 1975, 1990, and 2010. AB - Deposition of airborne sulfates and nitrates is considered to be an important factor in the decline of certain fish populations and of forest health in the eastern United States. A solution has been sought through legislation that mandates significant reductions in anthropogenic emissions of oxides of sulfur and nitrogen, precursors of sulfates and nitrates. This paper looks at the changes in sulfate deposition in the middle eastern United States from 1975 to 1990 and 2010 due to SO2 emission reductions brought about by 1970, 1977, and 1990 clean-air legislation. Recently developed emission inventories, together with a statistical, long-range transport model, were used to construct the estimates. The results show that sulfate deposition decreased over the middle eastern United States by about 25% between 1975 and 1990 and will decrease another 45% between 1990 and 2010-reductions commensurate with the overall decreases in SO2 emissions. The results further indicate that about half of the sulfur deposited in the environmentally sensitive southern Appalachian Mountains comes from states not a part of the southern Appalachian region. These estimates contain a measure of uncertainty due to uncertainty in emission estimates, the interannual variability of meteorology, and uncertainty arising from model assumptions and choices of oxidation and deposition rates. The model was able to reproduce about 10% of the variability in observations of wet sulfate deposition at over 100 sites over a 12-year period. PMID- 26355372 TI - Role of Concentration and Time of Day in Developing Ozone Exposure Indices for a Secondary Standard. AB - Evidence from exposure-response studies and a turbulent transfer model demonstrate that plant response is differential to concentration, duration, temporal pattern, and time of day of exposure. Reductions in productivity of crops and trees as seedlings are greater when plants are exposed to higher daytime ozone (O3) concentrations (0800-2000 hr standard time) or for longer durations. Primary evidence on the greater role of concentration comes from exposure-response experiments where plants are exposed to a series of pollutant concentrations in open-top chambers under field conditions. These studies demonstrate that the integrated exposure indices that give preferential weight to higher concentrations are better predictors of response than mean or peak indices. Evidence suggesting that mid-range O3 concentrations (0.05-0.09 parts per million, ppm) play a greater role than higher concentrations (>0.09 ppm) in biological response could not be justified. The time of day when O3 concentrations and atmospheric and stomatal conductances of gas exchange are optimal is a key to understanding plant response because plants respond only to O3 entering the leaf via stomata. A turbulent transfer model that describes the resistance of pollutant gas exchange from the atmosphere to the boundary layer of a forest canopy, as a function of micrometeorological variables, is developed to determine when flux of O3 is optimal. Based on meteorological and ambient air quality monitoring data at remote forest sites in the United States, it appears that O3 flux densities to the forest boundary layer are optimal during the 0800 2000 hr window. It is concluded that descriptors of ambient air quality for use in setting a federal standard should (1) cumulate hourly O3 concentrations, (2) give preferential weight to daytime concentrations between 0800 and 2000 hr, and (3) give preferential weight to higher O3 concentrations. PMID- 26355373 TI - Modeling Mercury Removal by Sorbent Injection. AB - Sorbents for removing mercury from flue gases of coal-fired power plants are presently being evaluated due to potential regulation of mercury emissions under Title III of the 1990 Clean Air Act Amendments. Laboratory tests have been conducted to evaluate the adsorption characteristics of potential sorbents and the effects of flue gas constituents on these characteristics. This paper presents a theoretical model that combines the adsorption characteristics measured in the lab with mass transfer considerations to predict mercury removal by the duct injection process in actual flue gas streams. The model was used to determine the effect of various sorbent properties on mercury removal when injecting a powdered sorbent upstream of either an electrostatic precipitator (ESP) or fabric filter. Mercury removal is expected to differ between these configurations since the mass transfer conditions are different in an ESP and fabric filter. The model was used to determine when mercury removal is limited by mass transfer and when it is limited by sorbent capacity. This information defines conditions when removal can be improved by reducing particle size or increasing sorbent capacity. In both cases, removal can be increased by injecting more sorbent. PMID- 26355374 TI - Case Studies on the Processes of Surface Ozone Pollution in Shanghai. AB - Typical processes of ozone (O3) pollution in the lower atmosphere in Shanghai are studied in the winter, summer, and autumn of 1994. Relationships between O3-NOx (nitrogen oxide) concentrations and meteorological parameters are analyzed in order to find meteorological indices corresponding to high O3 concentration days. Meteorological conditions favorable for high O3 concentrations usually appear when Shanghai is dominated by a high-pressure system in the lower atmosphere, while a northwestern current prevails over this area in the upper atmosphere. High O3 concentrations can occur when the wind speed is relatively high. O3 could increase rapidly on fog days. Temperatures influencing O3 concentrations are not as obvious in summer as in winter. Some possible mechanisms for the measurement results are suggested in this paper. PMID- 26355375 TI - The Magnitude of Bias in the Measurement of PM25 Arising from Volatilization of Particulate Nitrate from Teflon Filters. AB - Because the Federal Reference Method for PM25 specifies the collection of ambient particles on Teflon filters, we have examined the loss of a known volatile species, particulate nitrate, during sampling. Data are presented from two studies in southern California for which parallel samples were collected by different methods. Differences in collected nitrate are modeled using an evaporation model based on the work of Zhang and McMurry. The average nitrate obtained from sampling with Teflon filters was 28% lower on average than that measured by denuded nylon filters. In contrast, cascade impactor samples were within 5% of the denuded nylon filter on average. A simple model is presented that accounts for the particulate nitrate loss from Teflon filters either by scavenging nitric acid and ammonia in the sampler inlet or by heating the filter substrate during sampling. The observed magnitude of loss is explained by any of the following situations: (1) 100% nitric acid and ammonia vapor loss in the inlet, (2) 5 degrees C heating of the filter substrate above ambient temperature during sampling, or (3) a combination of these factors, such as 50% vapor loss in the inlet and 3 degrees C heating of the filter. PMID- 26355376 TI - Fate of Terpene Compounds in Activated Sludge Wastewater Treatment Systems. AB - Terpene-based cleaners are being widely used in industrial cleaning formulations because of their ability to replace suspected ozone-depleting chemicals such as 1,1,1-trichloroethane and 1,1,2-trichloro-1,2,2-trifluoroethane (CFC-113). Substitution of chlorinated solvents with ter-pene-based cleaners, however, is expected to result in increased discharges to wastewater from industrial operations. A pilot-scale study was conducted at the U.S. Environmental Protection Agency's (EPA) Test & Evaluation Facility in Cincinnati, OH, to quantify the fate of specific terpene compounds in the activated sludge wastewater treatment process. Biodegradation rates of terpenes were estimated from the difference between the influent terpene mass flow rates and the amounts volatilized to air, partitioned to waste sludge, and passed through the treatment process unchanged. Any chemical transformation of the terpene compounds studied was attributed to biodegradation. Analytical methods were developed to determine ter-pene concentrations in aqueous and gaseous media. The fate of two common terpene compounds (d-limonene and terpinolene) were evaluated in three identical pilot-scale systems: (1) a system with a high target spike range (2-10 mg/L), (2) a system with a low target spike range (0.5-2 mg/L), and (3) a control system (no spike). The study showed that the primary removal mechanism for the terpene compounds in the activated sludge process is biodegradation. Typically, greater than 90% of the mass of terpenes entering the aeration basin of the activated sludge process biodegrades to other compounds; volatilization from the reaction basin accounts for less than 10%, while loss to waste activated sludge and the secondary clarifier effluent accounts for less than 1%. PMID- 26355377 TI - Introduction to the Air & Waste Management Association's 29(th) Annual Critical Review. PMID- 26355378 TI - A Pleural Loose Body Mimicking a Pleural Tumor: A Case Report. AB - We present a rare case of a pleural loose body, thought to be a pedunculated pleural tumor, found incidentally in a 58-year-old female. Computed tomography showed a non-enhancing mass, which migrated along the mediastinum and paravertebral area. Thoracoscopic surgery revealed a 4 cm, soap-like mass that was found to be a fibrin body consisting of hyalinized collagen histopathologically. Mobility and the lack of contrast enhancement of a pleural mass are important clues to diagnosing this benign condition. PMID- 26355379 TI - Historical comparisons reveal multiple drivers of decadal change of an ecosystem engineer at the range edge. AB - Biogenic reefs are important for habitat provision and coastal protection. Long term datasets on the distribution and abundance of Sabellaria alveolata (L.) are available from Britain. The aim of this study was to combine historical records and contemporary data to (1) describe spatiotemporal variation in winter temperatures, (2) document short-term and long-term changes in the distribution and abundance of S. alveolata and discuss these changes in relation to extreme weather events and recent warming, and (3) assess the potential for artificial coastal defense structures to function as habitat for S. alveolata. A semi quantitative abundance scale (ACFOR) was used to compare broadscale, long-term and interannual abundance of S. alveolata near its range edge in NW Britain. S. alveolata disappeared from the North Wales and Wirral coastlines where it had been abundant prior to the cold winter of 1962/1963. Population declines were also observed following the recent cold winters of 2009/2010 and 2010/2011. Extensive surveys in 2004 and 2012 revealed that S. alveolata had recolonized locations from which it had previously disappeared. Furthermore, it had increased in abundance at many locations, possibly in response to recent warming. S. alveolata was recorded on the majority of artificial coastal defense structures surveyed, suggesting that the proliferation of artificial coastal defense structures along this stretch of coastline may have enabled S. alveolata to spread across stretches of unsuitable natural habitat. Long-term and broadscale contextual monitoring is essential for monitoring responses of organisms to climate change. Historical data and gray literature can be invaluable sources of information. Our results support the theory that Lusitanian species are responding positively to climate warming but also that short-term extreme weather events can have potentially devastating widespread and lasting effects on organisms. Furthermore, the proliferation of coastal defense structures has implications for phylogeography, population genetics, and connectivity of coastal populations. PMID- 26355380 TI - Tunable plasmon resonance and enhanced second harmonic generation and upconverted fluorescence of hemispheric-like silver core/shell islands. AB - We investigate tunable plasmon resonance and enhanced second harmonic generation (SHG) and up-converted fluorescence (UCF) of the hemispheric-like silver core/shell islands. The Ag, Ag/Ag2O, and Ag/Ag2O/Ag island films are prepared by using a sputtering technique. The SHG and UCF of the Ag/Ag2O/Ag core/shell islands near the percolating regime is enhanced 2.34 and 3.94 times compared to the sum of two individual counterparts of Ag/Ag2O core/shell and Ag shell islands. The ratio of SHG intensity induced by p- and s-polarization is 0.86 for the initial Ag islands and increase to 1.61 for the Ag/Ag2O/Ag core/shell samples. The tunable intensity ratio of SHG to UCF of the Ag islands treated by thermal and laser annealing processes is also observed. The physical mechanism of the enhanced SHG and UCF in the Ag/Ag2O/Ag core/shell islands is discussed. Our observations provide a new approach to fabricate plasmon-enhanced optical nonlinear nanodevices with tunable SHG and UCF. PMID- 26355381 TI - Creation of liquid-crystal periodic zigzags by surface treatment and thermal annealing. AB - The orientation control of soft matter to create a large area single domain is one of the most exciting research topics in materials science. Recently, this effort has been extended to fabricate two- or three-dimensional structures for electro-optical applications. Here, we create periodic zigzag structures in liquid crystals (LCs) using a combination of surface treatment and thermal annealing. The LC molecules in the nematic (N) phase were initially guided by the alignment layer of rubbed polymers, which were quenched and subsequently annealed in the smectic A (SmA) phase to create periodic zigzag structures that represent modulated layer structures. Direct investigation of the zigzags was performed using microscopy and diffraction techniques, showing the alternately arranged focal conic domains (FCDs) formed. The resulting macroscopic periodic structures will be of interest in further studies of the physical properties of soft matters. PMID- 26355383 TI - Red Blood Cell Transfusion: Precision vs Imprecision Medicine. PMID- 26355382 TI - Resource Utilization and Safety of Outpatient Management Following Intensive Induction or Salvage Chemotherapy for Acute Myeloid Leukemia or Myelodysplastic Syndrome: A Nonrandomized Clinical Comparative Analysis. AB - IMPORTANCE: Adults with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) typically remain hospitalized after induction or salvage chemotherapy until blood cell count recovery, with resulting prolonged inpatient stays being a primary driver of health care costs. Pilot studies suggest that outpatient management following chemotherapy might be safe and could reduce costs for these patients. OBJECTIVE: To compare safety, resource utilization, infections, and costs between adults discharged early following AML or MDS induction or salvage chemotherapy and inpatient controls. DESIGN: Nonrandomized, phase 2, single center study conducted at the University of Washington Medical Center. Over a 43 month period (January 1, 2011, through July 31, 2014), 178 adults receiving intensive AML or MDS chemotherapy were enrolled. After completion of chemotherapy, 107 patients met predesignated medical and logistical criteria for early discharge, while 29 met medical criteria only and served as inpatient controls. INTERVENTIONS: Early-discharge patients were released from the hospital at the completion of chemotherapy, and supportive care was provided in the outpatient setting until blood cell count recovery (median, 21 days; range, 2-45 days). Controls received inpatient supportive care (median, 16 days; range, 3-42 days). MAIN OUTCOMES AND MEASURES: We analyzed differences in early mortality, resource utilization including intensive care unit (ICU) days, transfusions per study day, and use of intravenous (IV) antibiotics per study day), numbers of infections, and total and inpatient charges per study day among early-discharge patients vs controls. RESULTS: Four of the 107 early-discharge patients and none of the 29 control patients died within 30 days of enrollment (P=.58). Nine early discharge patients (8%) but no controls required ICU-level care (P=.20). No differences were noted in the median daily number of transfused red blood cell units (0.27 vs 0.29; P=.55) or number of transfused platelet units (0.26 vs 0.29; P=.31). Early-discharge patients had more positive blood cultures (37 [35%] vs 4 [14%]; P=.04) but required fewer IV antibiotic days per study day (0.48 vs 0.71; P=.01). Overall, daily charges among early-discharge patients were significantly lower than for inpatients (median, $3840 vs $5852; P<.001) despite increased charges per inpatient day when readmitted (median, $7405 vs $5852; P<.001). CONCLUSIONS AND RELEVANCE: Early discharge following intensive AML or MDS chemotherapy can reduce costs and use of IV antibiotics, but attention should be paid to complications that may occur in the outpatient setting. PMID- 26355384 TI - Step-down vs. step-up noxious stimulation: differential effects on pain perception and patterns of brain activation. AB - BACKGROUND: We hypothesize that pain and brain responses are affected by changes in the presentation sequence of noxious stimuli that are, overall, identical in intensity and duration. METHODS: During functional magnetic resonance imaging (fMRI) scanning, 21 participants experienced three patterns of noxious stimulation: Up-type (step-up noxious stimulation, 15 s), Down-type (step-down noxious stimulation, 15 s), and Down-up-type (decreasing and increasing pattern of noxious stimulation, 15 s). The total intensity and duration of the three noxious stimulation patterns were identical, but the stimulation sequences were different. RESULTS: Pain and unpleasantness ratings in the Down- and Down-up-type noxious stimulations were lower than in the Up-type noxious stimulation. The left prefrontal cortex [(PFC, BA (Brodmann area) 10, (-45, 50, 1)] was more highly activated in the Down- and Down-up-type noxious stimulations than in the Up-type noxious stimulation. The S1, S2, insula, bilateral PFC (BA 46), and midcingulate cortex were more highly activated in the Up-type noxious stimulation than in the Down-type noxious stimulation. PFC BA 10 was located at an inferior level compared to the bilateral PFC BA 46 (Z axis = 1 for BA 10, compared to 22 and 25 for the right and left BA 46, respectively). When cortisol level was increased, the left hippocampal cortex, along with the left parahippocampal cortex, was greatly activated for the Up-type noxious stimulation. CONCLUSION: When pain cannot be avoided in clinical practice, noxious stimuli should be applied to patients in a step-down pattern that delivers the most intense pain first and the least intense pain last. PMID- 26355385 TI - Thymectomy is safe for myasthenia gravis patients: Analysis of the NSQIP database. AB - INTRODUCTION: The aim of this study was to determine thymectomy-associated morbidity and mortality outcomes among myasthenia gravis (MG) patients. METHODS: Patients undergoing thymectomy were identified from the National Surgical Quality Improvement Program database from 2005 to 2012 using Current Procedural Terminology codes. Patient demographics, clinical characteristics, and postoperative outcomes were stratified by MG diagnosis. Logistic regression was used to identify predictors for morbidity outcomes. The chi-square test was used to examine the association between MG diagnosis and surgical approach. RESULTS: A total of 1,148 subjects underwent thymectomy, and 108 had MG. Compared with control subjects, MG patients had a more severe American Society of Anesthesiologists physical classification and frailty index score, greater corticosteroid usage, and a higher rate of reintubation. There were no deaths among MG patients. The majority of MG patients underwent transsternal thymectomy. CONCLUSION: Although patients with MG have a greater preoperative morbidity and a higher frequency of reintubation, thymectomy was found to be a safe procedure overall. PMID- 26355386 TI - Sward characteristics, nutritive value and choice by cattle of conterminous monocultures of centipedegrass (Eremochloa ophiuroides) and bahiagrass (Paspalum notatum). AB - In south-western Japan, centipedegrass (Eremochloa ophiuroides; CG) offers a novel option for a warm-season perennial for grazing use in areas where bahiagrass (Paspalum notatum; BG) can be grown. However, the potential of CG as a forage has not been fully explored because of the short history as a forage crop. We conducted four experiments to evaluate CG (cv. TifBlair) in comparison with BG (cv. Pensacola) in terms of sward characteristics, nutritive value and choice by animals. In each experiment, four Japanese Black cows (Bos taurus) were individually allowed to graze conterminous monocultures of CG and BG (5 * 10 m each) for 30 min. Irrespective of regrowth durations and fertilizer rates, CG was consistently shorter, leafier and denser, contained lower acid detergent fiber and cellulose, and was preferred or equally selected by cows, as compared with BG. Furthermore, CG maintained sufficient levels of crude protein (80-89 g/kg DM) to ensure voluntary intake of ruminant animals under extended regrowth(?) and without fertilizer, whereas BG failed to do so (65 g/kg DM). CG provided higher digestible dry matter than BG when crude protein concentration exceeded 86 g/kg DM. The results indicate advantages of CG as a forage. PMID- 26355388 TI - Association between dietary vitamin C intake and risk of esophageal cancer: A dose-response meta-analysis. AB - While several epidemiological studies have investigated the association between vitamin C and risk of esophageal cancer, the results remain inconsistent. In the present study, a meta-analysis was conducted to assess the impact of dietary vitamin C intake on esophageal cancer risk. Online databases were searched up to March 29, 2015, for studies on the association between dietary vitamin C intake and esophageal cancer risk. Pooled risk ratios (RRs) or odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Dose response analyses were performed using the method of restricted cubic splines with four knots at percentiles of 5, 35, 65 and 95% of the distribution. Publication bias was estimated using Egger's tests and funnel plots. In all, 15 articles were included in this meta-analysis, including 20 studies, containing 7063 controls and 3955 cases of esophageal cancer. By comparing the highest vs. the lowest categories of vitamin C intake, we found that vitamin C was inversely associated with the risk of esophageal cancer [overall OR = 0.58, 95% CI = 0.49 0.68, I(2) = 56%]. A linear dose-response relationship was found. With an increase in dietary vitamin C intake of 50 mg/day, the risk of esophageal cancer statistically decreased by 13% (OR = 0.87, 95% CI = 0.80-0.93, p(linearity) = 0.0002). In conclusion, our analysis suggested that the higher intake of dietary vitamin C might have a protective effect against esophageal cancer. PMID- 26355387 TI - Vagal Intramuscular Arrays: The Specialized Mechanoreceptor Arbors That Innervate the Smooth Muscle Layers of the Stomach Examined in the Rat. AB - The fundamental roles that the stomach plays in ingestion and digestion notwithstanding, little morphological information is available on vagal intramuscular arrays (IMAs), the afferents that innervate gastric smooth muscle. To characterize IMAs better, rats were given injections of dextran biotin in the nodose ganglia, and, after tracer transport, stomach whole mounts were collected. Specimens were processed for avidin-biotin permanent labeling, and subsets of the whole mounts were immunohistochemically processed for c-Kit or stained with cuprolinic blue. IMAs (n = 184) were digitized for morphometry and mapping. Throughout the gastric muscle wall, IMAs possessed common phenotypic features. Each IMA was generated by a parent neurite arborizing extensively, forming an array of multiple (mean = 212) branches averaging 193 um in length. These branches paralleled, and coursed in apposition with, bundles of muscle fibers and interstitial cells of Cajal. Individual arrays averaged 4.3 mm in length and innervated volumes of muscle sheet, presumptive receptive fields, averaging 0.1 mm(3) . Evaluated by region and by muscle sheet, IMAs displayed architectural adaptations to the different loci. A subset (32%) of circular muscle IMAs issued specialized polymorphic collaterals to myenteric ganglia, and a subset (41%) of antral longitudinal muscle IMAs formed specialized net endings associated with the serosal boundary. IMAs were concentrated in regional patterns that correlated with the unique biomechanical adaptations of the stomach, specifically proximal stomach reservoir functions and antral emptying operations. Overall, the structural adaptations and distributions of the IMAs were consonant with the hypothesized stretch receptor roles of the afferents. PMID- 26355389 TI - IgG4-related tubulointerstitial nephritis: A prospective analysis. AB - AIMS: Immunoglobulin-G4 (IgG4)-related tubulo-interstitial nephritis (IgG4TIN) could be the first presentation of IgG4-related systemic disease. Most of the data is from the West or Japan and retrospective, with good patient outcome. METHODS: This study was carried out from April 2011 to July 2013. We report a prospective follow-up of 11 patients who presented with renal dysfunction and had histological diagnosis of IgG4TIN followed for a minimum period of 1 year or until end-stage renal disease. RESULTS: IgG4TIN constituted 0.28% of total renal biopsies and 6.5% of all tubulointerstitial nephritis. Patient ages ranged between 21 and 71 years with a male predominance. All the patients had renal dysfunction at presentation with a mean serum creatinine of 5.12 mg/dL. Proteinuria was subnephrotic except when there was coexisting membranous glomerulonephritis (36.4%). The mean 24-h urine protien excretion was 1.8 g. Serum IgG4 levels were elevated in 10 (90.9%) patients. Ten (90.9%) patients had renomegaly and one (9.1%) had focal renal mass. Extra-renal manifestations were present in seven (63.6%). Renal histology showed pattern A in five (45.5%), pattern B in four (36.3%) and pattern C in two (18.1%) patients. All but one patient (90.9%) received immunosuppressive therapy. Four (36.3%) achieved complete remission and three (27.2%) progressed to end stage renal disease. Two patients died due to infections while on steroid therapy. One patient with a mass had end stage renal disease for 12 months and did not improve with steroid therapy, and one (pattern C) had progressive chronic kidney disease on follow-up. CONCLUSION: IgG4TIN in an Indian cohort most often presents with rapidly progressive renal failure and less often has extra-renal organ involvement. On follow-up, patients can experience a more aggressive course with progression to end stage renal disease. PMID- 26355390 TI - Demographic compensation among populations: what is it, how does it arise and what are its implications? AB - Most species are exposed to significant environmental gradients across their ranges, but vital rates (survival, growth, reproduction and recruitment) need not respond in the same direction to those gradients. Opposing vital rate trends across environments, a phenomenon that has been loosely called 'demographic compensation', may allow species to occupy larger geographical ranges and alter their responses to climate change. Yet the term has never been precisely defined, nor has its existence or strength been assessed for multiple species. Here, we provide a rigorous definition, and use it to develop a strong test for demographic compensation. By applying the test to data from 26 published, multi population demographic studies of plants, we show that demographic compensation commonly occurs. We also investigate the mechanisms by which this phenomenon arises by assessing which demographic processes and life stages are most often involved. In addition, we quantify the effect of demographic compensation on variation in population growth rates across environmental gradients, a potentially important determinant of the size of a species' geographical range. Finally, we discuss the implications of demographic compensation for the responses of single populations and species' ranges to temporal environmental variation and to ongoing environmental trends, e.g. due to climate change. PMID- 26355391 TI - Platinum-conjugated antibodies for application in mass cytometry. AB - Mass cytometry has overcome limitations of fluorescent single cell cytometry by allowing for the measurement of up to currently ~40 different parameters on a single cell level. However, the cellular proteome comprises many more potential analytes, and current mass cytometry instrumentation allows for theoretically up to 121 different mass detection channels. The labeling of specific probes with appropriate metal ions is a significant hurdle for exploiting more of mass cytometry's analytical capacity. To this end, we here describe the labeling of antibody with natural abundance or isotopically purified platinum as formulated in cisplatin and circumventing the use of chelator-loaded polymers. We confirm the utility of cisplatin-antibody-conjugates for surface, intracellular, and phosphoepitope-specific immunophenotyping, as well as for application in cell surface CD45-based barcoding. Cisplatin-labeling of antibody increases the analytical capacity of the CyTOF((r)) platform by two channels based on available reagents, and has the potential to add a total of six channels for detection of specific probes, thus helping to better extend the analytical mass range of mass cytometers. PMID- 26355392 TI - Fusion of PDGFRB to MPRIP, CPSF6, and GOLGB1 in three patients with eosinophilia associated myeloproliferative neoplasms. AB - In eosinophilia-associated myeloproliferative neoplasms (MPN-eo), constitutive activation of protein tyrosine kinases (TK) as consequence of translocations, inversions, or insertions and creation of TK fusion genes is recurrently observed. The most commonly involved TK and their potential TK inhibitors include PDGFRA at 4q12 or PDGFRB at 5q33 (imatinib), FGFR1 at 8p11 (ponatinib), and JAK2 at 9p24 (ruxolitinib). We here report the identification of three new PDGFRB fusion genes in three male MPN-eo patients: MPRIP-PDGFRB in a case with t(5;17)(q33;p11), CPSF6-PDGFRB in a case with t(5;12)(q33;q15), and GOLGB1-PDGFRB in a case with t(3;5)(q13;q33). The fusion proteins identified by 5'-rapid amplification of cDNA ends polymerase chain reaction (PCR) or DNA-based long distance inverse PCR are predicted to contain the TK domain of PDGFRB. The partner genes contain domains like coiled-coil structures, which are likely to cause dimerization and activation of the TK. In all patients, imatinib induced rapid and durable complete remissions. PMID- 26355394 TI - National identification and attitudes towards Russian immigrants in Finland: Investigating the role of perceived threats and gains. AB - In this cross-sectional study, we examined the relationship between national identification of majority Finns (nation-wide probability sample, N = 335) and their attitudes towards Russian immigrants living in Finland. As previous research indicates both possibilities, we tested whether this relationship was moderated or mediated by threats and gains perceived to result from immigration. The results supported the mediation hypothesis; those individuals who identified stronger with their national ingroup perceived more threats than gains related to increased immigration and these perceptions, in turn, were associated with more negative attitudes towards immigrants. The role of realistic as opposed to symbolic threats and gains was particularly pronounced. The implications of the results are discussed in terms of their theoretical relevance and practical means to improve intergroup relations, with a particular focus on the relations between Finns and Russian immigrants in Finland. PMID- 26355393 TI - Accuracy of caregivers' recall of hospital admissions: implications for research. AB - AIM: To determine the accuracy of caregivers' recall of hospital admissions in early childhood. METHODS: Prospective cohort study of babies born at risk of neonatal hypoglycaemia at Waikato Hospital, New Zealand, a regional public hospital and sole provider of acute inpatient care to over 100,000 children. Caregivers' recall of children's hospital admissions up to 4.5 years was compared with medical records. Accuracy of recall was related to neonatal and socio demographic characteristics. RESULTS: Of 267 children, 179 (67%) visited hospital and 106 (40%) were admitted at least once. The most frequent reasons for admission were for respiratory (29%) and gastrointestinal (18%) problems. Of 106 children admitted to hospital, 27 (25%) caregivers did not recall the admission and only 37 (35%) accurately recalled the number of admissions. The accuracy of recall was lower for gastrointestinal (38%) and surgical (40%) problems, while recall of respiratory (64%) and ear, nose and throat (60%) admissions was more accurate. Low socio-economic status and multiple admissions were associated with less accurate recall of number of admissions. CONCLUSION: Caregivers do not accurately report hospital admissions. Questionnaire data about use of hospital facilities should be interpreted cautiously and may not be sufficiently accurate for use in research studies. PMID- 26355397 TI - A systematic review and meta-evaluation of adolescent smoking cessation interventions that utilized nicotine replacement therapy. PMID- 26355395 TI - Role of nitric oxide in the radiation-induced bystander effect. AB - Cells that are not irradiated but are affected by "stress signal factors" released from irradiated cells are called bystander cells. These cells, as well as directly irradiated ones, express DNA damage-related proteins and display excess DNA damage, chromosome aberrations, mutations, and malignant transformation. This phenomenon has been studied widely in the past 20 years, since its first description by Nagasawa and Little in 1992, and is known as the radiation-induced bystander effect (RIBE). Several factors have been identified as playing a role in the bystander response. This review will focus on one of them, nitric oxide (NO), and its role in the stimulation and propagation of RIBE. The hydrophobic properties of NO, which permit its diffusion through the cytoplasm and plasma membranes, allow this signaling molecule to easily spread from irradiated cells to bystander cells without the involvement of gap junction intercellular communication. NO produced in irradiated tissues mediates cellular regulation through posttranslational modification of a number of regulatory proteins. The best studied of these modifications are S-nitrosylation (reversible oxidation of cysteine) and tyrosine nitration. These modifications can up- or down-regulate the functions of many proteins modulating different NO-dependent effects. These NO-dependent effects include the stimulation of genomic instability (GI) and the accumulation of DNA errors in bystander cells without direct DNA damage. PMID- 26355396 TI - Dynamic differences in oxidative stress and the regulation of metabolism with age in visceral versus subcutaneous adipose. AB - Once thought only as storage for excess nutrients, adipose tissue has been shown to be a dynamic organ implicated in the regulation of many physiological processes. There is emerging evidence supporting differential roles for visceral and subcutaneous white adipose tissue in maintaining health, although how these roles are modulated by the aging process is not clear. However, the proposed beneficial effects of subcutaneous fat suggest that targeting maintenance of this tissue could lead to healthier aging. In this study, we tested whether alterations in adipose function with age might be associated with changes in oxidative stress. Using visceral and subcutaneous adipose from C57BL/6 mice, we discovered effects of both age and depot location on markers of lipolysis and adipogenesis. Conversely, accumulation of oxidative damage and changes in enzymatic antioxidant expression with age were largely similar between these two depots. The activation of each of the stress signaling pathways JNK and MAPK/ERK was relatively suppressed in subcutaneous adipose tissue suggesting reduced sensitivity to oxidative stress. Similarly, pre-adipocytes from subcutaneous adipose were significantly more resistant than visceral-derived cells to cell death caused by oxidative stress. Cellular respiration in visceral-derived cells was dramatically higher than in cells derived from subcutaneous adipose despite little evidence for differences in mitochondrial density. Together, our data identify molecular mechanisms by which visceral and subcutaneous adipose differ with age and suggest potential targetable means to preserve healthy adipose aging. PMID- 26355398 TI - Modeling motivations for non-medical use of prescription drugs. AB - INTRODUCTION: Non-medical use of prescription drugs (NMUPD) is a growing problem among college-aged individuals. Motivations for use of a substance have been shown to predict consumption behavior across a variety of substances, but research on motivations for engaging in NMUPD is limited. We hypothesize that Confirmatory Factor Analysis (CFA) would support a two-factor latent structure for motivations (self-treatment and recreational) for NMUPD across three classes of drugs (stimulants, tranquilizers and sedatives, and pain relievers). METHODS: Data were collected from 1016 undergraduates attending a large southeastern university via an online survey. Motivations for use were subjected to a CFA for those participants who reported past-year use of each drug class (tranquilizer and sedative use n=138, pain reliever use n=189, and stimulant use n=258). RESULTS: Model fit varied across drug class. A two-factor model emerged for both pain relievers and stimulants, and each factor was positively correlated with one another and with frequency of use for both drug classes. A two-factor model was not a good fit for tranquilizers and sedatives. CONCLUSIONS: Motives for NMUPD are a relatively understudied construct. Although our initial results suggest that a proposed framework consisting of self-treatment and recreational motives might have some utility in explaining the use of stimulants and pain relievers, more research is needed to characterize motives for tranquilizers and sedatives. Additional research is also needed to develop assessment measures that capture the full range of motives for all three classes of NMUPD. PMID- 26355399 TI - A Historical Tale of Two Lymphomas: Part II: Non-Hodgkin lymphoma. PMID- 26355400 TI - Frequency and Appropriateness of Fasting Orders in the Hospital. AB - OBJECTIVE: To evaluate the frequency and appropriateness of nil per os (nothing by mouth) (NPO) orders and determine the number of meals missed because of these orders among hospitalized patients. PATIENTS AND METHODS: We retrospectively analyzed inpatient NPO orders at an academic institution in the United States. The frequency and duration of NPO orders and the number of meals missed because of these orders were assessed for adult patients admitted to the hospital medicine services from January 1, 2013, through December 31, 2013, with a hospital stay of 2 or more and 30 or fewer days. Two blinded reviewers assessed if the order could be avoided or the period shortened for a random sample of NPO orders of 120 or more minutes' duration that were written for patients on the general medicine ward. RESULTS: A total of 3641 NPO orders were identified. At least one NPO order was placed in 46.6% of the admissions (2211 of 4743). The median duration of NPO orders was 12.8 hours (interquartile range, 9.2-17.3 hours), resulting in 2 (interquartile range, 1-4) missed meals. Of 1130 NPO orders reviewed, 263 (23.3%; 95% CI, 20.9%-25.8%) were deemed avoidable (kappa statistic, 0.68), and 482 (42.7%) were unavoidable but led to more missed meals than needed. Taken together, patients could have had 44.8% of the meals (1085 of 2424; 95% CI, 42.8%-46.7%) missed due to NPO orders. CONCLUSION: Approximately half of the patients admitted to the hospital medicine services experienced a period of fasting. One in 4 NPO orders and nearly half of missed meals could have been avoided. Further study is warranted to assess the generalizability of our findings. PMID- 26355401 TI - Nonceliac Gluten Sensitivity. AB - Nonceliac gluten sensitivity (NCGS) is the clinical term used to describe gastrointestinal (GI) and/or extraintestinal symptoms associated with gluten ingestion. The prevalence of NCGS is unknown. The condition has clinical features that overlap with those of celiac disease (CD) and wheat allergy (WA). The pathophysiologic process in NCGS is thought to be through an innate immune mechanism, whereas CD and WA are autoimmune- and allergen-mediated, respectively. However, dietary triggers other than gluten, such as the fermentable oligosaccharides, disaccharides, monosaccharides, and polyols, have been implicated. Currently, no clinical biomarker is available to diagnose NCGS. Exclusion of CD and WA is necessary in the evaluation of a patient suspected to have NCGS. The onset of symptoms in patients with NCGS can occur within hours or days of gluten ingestion. Patients with NCGS have GI and extraintestinal symptoms that typically disappear when gluten-containing grains are eliminated from their diets. However, most patients suspected to have NCGS have already initiated a gluten-free diet at the time of an evaluation. A gluten elimination diet followed by a monitored open challenge of gluten intake to document recurrence of GI and/or extraintestinal symptoms can sometimes be helpful. If NCGS is strongly suggested, then a skilled dietitian with experience in counseling on gluten-free diets can provide proper patient education. Additional research studies are warranted to further our understanding of NCGS, including its pathogenesis and epidemiology, and to identify a biomarker to facilitate diagnosis and patient selection for proper management. PMID- 26355402 TI - 44-Year-Old Man With Left-Sided Paresthesias and Homonymous Hemianopsia. PMID- 26355403 TI - Essential Thrombocythemia and Polycythemia Vera: Focus on Clinical Practice. AB - Bone marrow (BM) morphologic features remain the cornerstone of diagnosis in both essential thrombocythemia (ET) and polycythemia vera (PV). In addition, recently discovered mutations, such as JAK2, CALR, and MPL, have proven useful in facilitating the diagnostic process. A JAK2 mutation is expected in PV, and its absence makes the diagnosis unlikely. However, JAK2 mutations also occur in about 60% of patients with ET, which underlines the need for BM examination in distinguishing JAK2-mutated ET from PV when the hemoglobin/hematocrit level is diagnostically equivocal (ie, as in "masked" PV). Most patients with JAK2 unmutated ET express CALR or MPL mutations, with respective estimated incidences of 22% and 3%, while approxmately 15% are wild-type for all 3 mutations (ie, they are triple-negative). As such, CALR first, followed by MPL if CALR is absent, mutation screening is appropriate in the diagnostic work-up of JAK2-unmutated ET but does not replace the need for BM morphologic examination in (1) confirming the diagnosis in triple-negative ET and (2) distinguishing ET from other myeloproliferative neoplasms that share the same mutations, including masked PV and early/prefibrotic myelofibrosis. Young patients (aged < 60 years) with ET or PV and no history of thrombosis are conventionally regarded as having "low-risk" disease. First-line treatment in low-risk PV is phlebotomy to achieve a hematocrit target of 45% and low-dose aspirin, and first-line treatment in ET is observation alone in the absence of additional risk factors for arterial thrombosis (ie, JAK2 mutation and cardiovascular risk factors) or low-dose aspirin therapy, once or twice daily, in the presence of one or both of these risk factors, respectively. Cytoreductive therapy is indicated in high-risk (patients aged >= 60 years or a history of thrombosis) PV or ET in the form of hydroxyurea as first-line and interferon alfa or busulfan as second-line drugs of choice. We do not use ruxolitinib in patients with PV unless they have severe pruritus or symptomatic splenomegaly that is proved to be refractory to hydroxyurea, interferon alfa, and busulfan. PMID- 26355404 TI - In reply--Long-term Efficacy and Safety of Exenatide Treatment. PMID- 26355405 TI - Long-term Efficacy and Safety of Exenatide Treatment. PMID- 26355406 TI - Hyponatremia Due to Thyrotropin Deficiency: A Fairy Tale? PMID- 26355407 TI - Incorporating Palliative Care Into the Dialysis Unit Affects Patterns Near the End of Life. PMID- 26355408 TI - Erdheim-Chester Disease. PMID- 26355410 TI - 71-Year-Old Woman With Abdominal Pain. PMID- 26355411 TI - Reclamation of zinc-contaminated soil using a dissolved organic carbon solution prepared using liquid fertilizer from food-waste composting. AB - A liquid fertilizer obtained through food-waste composting can be used for the preparation of a dissolved organic carbon (DOC) solution. In this study, we used the DOC solutions for the remediation of a Zn-contaminated soil (with Zn concentrations up to 992 and 757 mg kg(-1) in topsoil and subsoil, respectively). We then determined the factors that affect Zn removal, such as pH, initial concentration of DOC solution, and washing frequency. Measurements using a Fourier Transform infrared spectrometer (FT-IR) revealed that carboxyl and amide were the major functional groups in the DOC solution obtained from the liquid fertilizer. Two soil washes using 1,500 mg L(-1) DOC solution with a of pH 2.0 at 25 degrees C removed about 43% and 21% of the initial Zn from the topsoil and subsoil, respectively. Following this treatment, the pH of the soil declined from 5.4 to 4.1; organic matter content slightly increased from 6.2 to 6.5%; available ammonium (NH4(+)-N) content increased to 2.4 times the original level; and in the topsoil, the available phosphorus content and the exchangeable potassium content increased by 1.65 and 2.53 times their initial levels, respectively. PMID- 26355412 TI - Treatment of landfill leachate using immobilized Phanerochaete chrysosporium loaded with nitrogen-doped TiO2 nanoparticles. AB - This study investigated the performance of immobilized Phanerochaete chrysosporium loaded with nitrogen-doped TiO2 nanoparticles in the treatment of raw landfill leachate with a very low biodegradability ratio (BOD5/COD) of 0.09. The effects of various operating parameters, such as initial chemical oxygen demand (COD) concentration, pH, temperature, and biosorbent dosage, were evaluated with respect to the removal efficiency of total organic carbon (TOC) and ammonia nitrogen (NH3-N). For the immobilized biosorbents, an optimum pH of 6.0 for TOC and 7.0 for NH3-N were found suitable for TOC and NH3-N removal at temperature of 37 degrees C, respectively. The most superior removal efficiencies of TOC and NH3-N of landfill leachate were over 75% and 74% in 72 h at an initial COD concentration of 200 mg L(-1), respectively. In addition, heavy metals were partly removed by the immobilized biosorbents during the process of landfill leachate treatment. The species and mass percentage of organic compounds in landfill leachate after the treatment were found to have considerably declined according to the gas chromatography coupled with mass spectrometry (GC-MS) system. These results indicate that the immobilized P. chrysosporium loaded with nitrogen-doped TiO2 nanoparticles could be a convenient and efficient method for the treatment of landfill leachate. PMID- 26355414 TI - Ethical Implications of the Cost of Molecularly Targeted Therapies. PMID- 26355413 TI - Lead and copper immobilization in a shooting range soil using soybean stover- and pine needle-derived biochars: Chemical, microbial and spectroscopic assessments. AB - Biochar (BC) could be a potential candidate for the remediation of metal contaminated soil. Mechanistic understandings are needed for the appropriate selection of BC and investigating molecular microbial ecological interactions. The soybean stover-derived BCs were more effective in immobilizing Pb (88%) and Cu (87%) than the pine needle-derived BCs in a contaminated shooting range soil. The sequential chemical extractions indicated that BCs stimulated the geochemical transformation of metal species. Spectroscopic investigations using scanning electron microscopic elemental dot mapping and extended X-ray absorption fine structure spectroscopic measurements showed that Pb in the BCs amended soils was immobilized by the formation of stable chloropyromorphite. Soil organic C and microbial activity were also enhanced by BC. The non-labile C fraction in the soil amended with BCs produced at 700 degrees C was increased. Biochars showed less impact on the bacterial community than feedstock biomass as promulgated by the pyrosequencing of 16S rRNA gene. The feedstock type (namely soybean stover and pine needles) was the main factor influencing the BCs efficacy on metals' (im) mobilization and bacterial health in soils. PMID- 26355415 TI - Multiplex real-time PCR assays for detection of eight Shiga toxin-producing Escherichia coli in food samples by melting curve analysis. AB - Shiga toxin-producing Escherichia coli (STEC) are pathogenic strains of E. coli that can cause bloody diarrhea and kidney failure. Seven STEC serogroups, O157, O26, O45, O103, O111, O121 and O145 are responsible for more than 71% of the total infections caused by this group of pathogens. All seven serogroups are currently considered as adulterants in non-intact beef products in the U.S. In this study, two multiplex melt curve real-time PCR assays with internal amplification controls (IACs) were standardized for the detection of eight STEC serogroups. The first multiplex assay targeted E. coli serogroups O145, O121, O104, and O157; while the second set detected E. coli serogroups O26, O45, O103 and O111. The applicability of the assays was tested using 11 different meat and produce samples. For food samples spiked with a cocktail of four STEC serogroups with a combined count of 10 CFU/25 g food, all targets of the multiplex assays were detected after an enrichment period of 6h. The assays also worked efficiently when 325 g of food samples were spiked with 10 CFU of STECs. The assays are not dependent on fluorescent-labeled probes or immunomagnetic beads, and can be used for the detection of eight STEC serogroups in less than 11h. Routine preliminary screening of STECs in food samples is performed by testing for the presence of STEC virulence genes. The assays developed in this study can be useful as a first- or second-tier test for the identification of the eight O serogroup-specific genes in suspected food samples. PMID- 26355416 TI - An atomic finite element model for biodegradable polymers. Part 1. Formulation of the finite elements. AB - Molecular dynamics (MD) simulations are widely used to analyse materials at the atomic scale. However, MD has high computational demands, which may inhibit its use for simulations of structures involving large numbers of atoms such as amorphous polymer structures. An atomic-scale finite element method (AFEM) is presented in this study with significantly lower computational demands than MD. Due to the reduced computational demands, AFEM is suitable for the analysis of Young's modulus of amorphous polymer structures. This is of particular interest when studying the degradation of bioresorbable polymers, which is the topic of an accompanying paper. AFEM is derived from the inter-atomic potential energy functions of an MD force field. The nonlinear MD functions were adapted to enable static linear analysis. Finite element formulations were derived to represent interatomic potential energy functions between two, three and four atoms. Validation of the AFEM was conducted through its application to atomic structures for crystalline and amorphous poly(lactide). PMID- 26355417 TI - Electrochemical and ab initio investigations to design a new phenothiazine based organic redox polymeric material for metal-ion battery cathodes. AB - Different N-substituted phenothiazines have been synthesized and their electrochemical behavior has been investigated in CH3CN in order to design the best polyphenothiazine based cathodic material candidate for lithium batteries. These compounds exhibit two successive reversible one-electron oxidation processes. Ab initio calculations demonstrate that the potential of the first process is a result of both the hybridization effects between the substituent and the phenothiazine unit as well as the change of conformation of the phenothiazine heterocycle during the oxidation process. More specifically, we show that an asymmetric molecular orbital spreading throughout an external cycle of the phenothiazine unit and the alkyl fragment is formed only if the alkyl fragment is long enough (from the methyl moiety onwards) and is at the origin of the bent conformation for N-substituted phenothiazines during oxidation. Electrochemical investigations supported by ab initio calculations allow the selection of a phenothiazinyl unit which is then polymerized by a Suzuki coupling strategy to avoid the common solubilization issue in carbonate-based liquid electrolytes of lithium cells. The first electrochemical measurements performed show that phenothiazine derivatives pave the way for a promising family of redox polymers intended to be used as organic positives for lithium batteries. PMID- 26355418 TI - Effects of Priming and Pacing Strategy on Oxygen-Uptake Kinetics and Cycling Performance. AB - PURPOSE: To assess whether combining prior "priming" exercise with an all-out pacing strategy is more effective at improving oxygen-uptake (VO2) kinetics and cycling performance than either intervention administered independently. METHODS: Nine men completed target-work cycling performance trials using a self-paced or all-out pacing strategy with or without prior severe-intensity (70%Delta) priming exercise. Breath-by-breath pulmonary VO2 and cycling power output were measured during all trials. RESULTS: Compared with the self-paced unprimed control trial (22 +/- 5 s), the VO2 mean response time (MRT) was shorter (VO2 kinetics were faster) with all-out pacing (17 +/- 4 s) and priming (17 +/- 3 s), with the lowest VO2 MRT observed when all-out pacing and priming were combined (15 +/- 4 s) (P < .05). However, total O2 consumed and end-exercise VO2 were only higher than the control condition in the primed trials (P < .05). Similarly, cycling performance was improved compared with control (98 +/- 11 s) in the self-paced primed (93 +/- 8 s) and all-out primed (92 +/- 8 s) trials (P < .05) but not the all-out unprimed trial (97 +/- 5 s; P > .05). CONCLUSIONS: These findings suggest that combining an all-out start with severe-intensity priming exercise additively improves VO2 MRT but not total O2 consumption and cycling performance since these were improved by a similar magnitude in both primed trials relative to the self paced unprimed control condition. Therefore, these results support the use of priming exercise as a precompetition intervention to improve oxidative metabolism and performance during short-duration high-intensity cycling exercise, independent of the pacing strategy adopted. PMID- 26355419 TI - Discovery and functional analysis of a 4th electron-transferring tryptophan conserved exclusively in animal cryptochromes and (6-4) photolyases. AB - A 4th electron transferring tryptophan in animal cryptochromes and (6-4) photolyases is discovered and functionally analyzed by transient absorption. It yields a much longer-lived flavin-tryptophan radical pair than the mere tryptophan triad in related flavoproteins, questioning the putative role of the primary light reaction of cryptochrome in animal magnetoreception. PMID- 26355420 TI - Reliability of measuring pelvic floor elevation with a diagnostic ultrasonic imaging device. AB - [Purpose] The purpose of this study was to investigate the reliability of measuring the amount of pelvic floor elevation during pelvic and abdominal muscle contraction with a diagnostic ultrasonic imaging device. [Subjects] The study group comprised 11 healthy women without urinary incontinence or previous birth experience. [Methods] We measured the displacement elevation of the bladder base during contraction of the abdominal and pelvic floor muscles was measured using a diagnostic ultrasonic imaging device. The exercise was a four-part operation undertaken with the subjects in the lateral position. The reliability analysis included use of the interclass correlation coefficient (ICC) was used to assess the reliability. [Results] ICC (1.1) values for the pelvic floor elevation measurement with a diagnostic ultrasonic imaging device were 0.98 [contraction of the transversus abdominis (TrA) muscle], 0.99 [contraction of pelvic floor muscles (PFMs)], 0.98 (co-contraction of the TrA and PFMs), and 0.98 (resistance of the TrA and PFMs). This study proved the reliability of the method because the coefficient of reliability was 0.97 or more for all of the measurements, even for those during exercise. [Conclusion] The diagnostic ultrasonic imaging device measures pelvic floor elevation with high reliability. PMID- 26355421 TI - Caseous Necrosis of Mitral Annulus. AB - Masses or mass-like lesions located in proximity to mitral valve encompass a wide range of differential diagnoses including neoplasias, abscesses, thrombi, and rarely caseous calcification of mitral annulus. Due to asymptomatic presentation, its diagnosis is usually incidental. Echocardiography is the first choice of imaging in evaluation. Cardiac computed tomography (CT) is helpful in establishing diagnosis by showing dense calcifications while cardiac magnetic resonance imaging (MRI) is used primarily as a problem solving tool. Imaging in evaluation of mitral annulus caseous calcification is essential in order to prevent unnecessary operations. PMID- 26355422 TI - Ebola Virus Disease--Sierra Leone and Guinea, August 2015. AB - The Ebola virus disease (Ebola) outbreak in West Africa began in late 2013 in Guinea (1) and spread unchecked during early 2014. By mid-2014, it had become the first Ebola epidemic ever documented. Transmission was occurring in multiple districts of Guinea, Liberia, and Sierra Leone, and for the first time, in capital cities (2). On August 8, 2014, the World Health Organization (WHO) declared the outbreak to be a Public Health Emergency of International Concern (3). Ministries of Health, with assistance from multinational collaborators, have reduced Ebola transmission, and the number of cases is now declining. While Liberia has not reported a case since July 12, 2015, transmission has continued in Guinea and Sierra Leone, although the numbers of cases reported are at the lowest point in a year. In August 2015, Guinea and Sierra Leone reported 10 and four confirmed cases, respectively, compared with a peak of 526 (Guinea) and 1,997 (Sierra Leone) in November 2014. This report details the current situation in Guinea and Sierra Leone, outlines strategies to interrupt transmission, and highlights the need to maintain public health response capacity and vigilance for new cases at this critical time to end the outbreak. PMID- 26355423 TI - T-cell phenotype and function following a first cART regimen containing either a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor in HIV infected late presenters: results from a retrospective, ex vivo study. AB - BACKGROUND: We aimed to comparatively assess darunavir/ritonavir (DRV/r) and efavirenz (EFV)-based first-line cART regimens in the reconstitution of T-cell phenotype and function in HIV-infected, late presenter subjects. METHODS: Retrospective, ex vivo study on stored peripheral blood mononuclear cell samples of cART-naive, HIV-infected individuals with CD4(+) T-cell counts <50>250/ul upon cART initiation with either DRV/r or EFV as third drugs of standard antiretroviral regimens. CD4(+) and CD8(+) T-cell maturation (CCR7/CD45RA) and proliferation (Ki67), CD8(+) T-cell activation (CD38/HLA-DR) as well as HIV- and cytomegalovirus (CMV)-specific responses (CD4/CD8/IL-2/IFN-gamma) were studied by flow cytometry at baseline (T0), T3, T6 and T12 months. Soluble inflammatory markers (IL-6 and sCD14) were measured in plasma at T0 and T12. Wilcoxon and Mann Whitney tests were used for statistics. RESULTS: A total of 19 patients started DRV/r and 15 EFV. Both regimens accounted for suppression of the HIV RNA load (<40 copies/ml), reconstitution of absolute CD4(+) T-cells and CD4(+)/CD8(+) T cell ratio. All study participants displayed a significant decrease of activated HLA-DR(+)CD38(+) CD8(+) T-cells at all study time points, yet no differences were found between study groups in T-cell activation and maturation phenotype. From a functional standpoint, only individuals receiving DRV/r displayed transitory recovery of HIV-specific IL-2(+)IFN-gamma(-) CD4(+) T-cells (T3: P=0.006) and IL 2(-)IFN-gamma(+) CD8(+) T-cells (T3: P=0.032). CONCLUSIONS: DRV/r- and EFV-based regimens have an equal effect on T-cell phenotype and function in HIV late presenters. A temporary restoration of HIV-specific T-cell immunity early in the course of therapy with DRV/r possibly implies a more effective control over HIV in the first months following a PI/r-based regimen, even at late stage of disease. PMID- 26355425 TI - Effects of task-oriented training on upper extremity function and performance of daily activities by chronic stroke patients. AB - [Purpose] The aim of this study was to determine the effects that task-oriented training has on upper extremity function and performance of daily activities by chronic stroke patients. [Subjects and Methods] Task-oriented training was applied to two chronic hemiplegic patients in this research. The training was provided to each patient for 30 minutes a day, five times a week for two weeks. The treatment program included six different types of training that could be performed by the patients themselves. Evaluation was performed four times, that is, once a week for three weeks before the intervention and once after the intervention. The change in upper extremity function was measured with the Manual Function Test, and the change in performance of daily activity was measured with the Functional Independence Measure. [Results] The upper extremity function of both subjects was improved after application of task-oriented training. However, in the performance of daily activities, subject one showed improvement compared to with before the intervention, whereas subject two showed the same results. [Conclusion] This research confirmed that two weeks of task-oriented training for chronic stroke patients is effective for improvement of upper extremity function and performance of daily activities by chronic stroke patients. PMID- 26355424 TI - Immune Homeostasis in Epithelial Cells: Evidence and Role of Inflammasome Signaling Reviewed. AB - The epithelium regulates the interaction between the noxious xenogenous, as well as the microbial environment and the immune system, not only by providing a barrier but also by expressing a number of immunoregulatory membrane receptors, and intracellular danger sensors and their downstream effectors. Amongst these are a number of inflammasome sensor subtypes, which have been initially characterized in myeloid cells and described to be activated upon assembly into multiprotein complexes by microbial and environmental triggers. This review compiles a vast amount of literature that supports a pivotal role for inflammasomes in the various epithelial barriers of the human body as essential factors maintaining immune signaling and homeostasis. PMID- 26355426 TI - How consistent are associations between stunting and child development? Evidence from a meta-analysis of associations between stunting and multidimensional child development in fifteen low- and middle-income countries. AB - OBJECTIVE: Despite documented associations between stunting and cognitive development, few population-level studies have measured both indicators in individual children or assessed stunting's associations with other developmental domains. DESIGN: Meta-analysis using publicly available data from fifteen Multiple Indicator Cluster Surveys (MICS-4) to assess the association between stunting and development, controlling for maternal education, family wealth, books in the home, developmentally supportive parenting and sex of the child, stratified by country prevalence of breast-feeding ('low BF'<90 %, 'high BF' >=90 %). Ten-item Early Childhood Development Index (ECDI) scores assessed physical, learning, literacy/numeracy and socio-emotional developmental domains. Children on track in three or four domains were considered 'on-track' overall. SETTING: Fifteen low- and middle-income countries. SUBJECTS: Publically available data from 58 513 children aged 36-59 months. RESULTS: Severe stunting (height-for-age Z-score <-3) was negatively associated with on-track development (OR=0.75; 95 % CI 0.67, 0.83). Any stunting (Z-score <-2) was negatively associated with on track development in countries with high BF prevalence (OR=0.82; 95 % CI 0.75, 0.89). Severe and any stunting were negatively associated with physical development (OR=0.77; 95 % CI 0.66, 0.89 and OR=0.82; 95 % CI 0.74, 0.91, respectively) and literacy/numeracy development in high BF countries (OR=0.45; 95 % CI 0.38, 0.53 and OR=0.59, 95 % CI 0.51, 0.68, respectively), but not low BF countries (OR=0.93; 95 % CI 0.70, 1.23 and OR=0.95, 95 % CI 0.79, 1.12, respectively). Any stunting was negatively associated with learning (OR=0.79; 95 % CI 0.72, 0.88). There was no clear association between stunting and socio emotional development. CONCLUSIONS: Stunting is associated with many but not all developmental domains across a diversity of countries and cultures. However, associations varied by country breast-feeding prevalence and developmental domain. PMID- 26355427 TI - Hepatitis C Recurrence after Orthotopic Liver Transplantation: Mechanisms and Management. AB - Chronic Hepatitis C (HCV) infection is the leading indication for orthotopic liver transplantation and recurrence is nearly universal. Chronic HCV infection is frequently established through evasion of the innate immune system. Priming of adaptive immune responses modulate the severity and rate of fibrosis progression. Those with demonstrable viremia entering the transplant period uniformly suffer recurrence post-transplant. Progression to cirrhosis is accelerated post transplant secondary to systemic immunosuppression. In addition, a number of factors, including donor, host, and viral characteristics, influence severity and rate of fibrosis progression. Interferon-based therapy, the previous standard of care, in those with advanced cirrhosis or post-transplant has been limited by a number of issues. These include a relative lack of efficacy and poor tolerability with higher incidence of infection and anemia. Recently, approval of direct acting antivirals have ushered in a new era in HCV therapeutics and have applicability in these special populations. Their use immediately prior to or post-transplant is expected to improve both morbidity and mortality. PMID- 26355428 TI - Infectious diseases linked to cross-contamination of flexible endoscopes. AB - Flexible endoscopes are widely used to examine, diagnose, and treat medical disorders. While the risk of endoscopy-related transmission of infection is estimated to be very low, more health care-associated infections are related to contaminated endoscopes than to any other medical device. Flexible endoscopes can get highly contaminated with microorganisms, secretions and blood during use. The narrow lumens and multiple internal channels make the cleaning of flexible endoscopes a complex and difficult task. Despite the availability of international, national and local endoscope reprocessing guidelines, contamination and transmission of microorganisms continue to occur. These transmissions are mostly related to the use of defective equipment, endoscope reprocessing failures, and noncompliance with recommended guidelines. This article presents an overview of publications about case reports and outbreaks related to contamination of flexible endoscopes. PMID- 26355429 TI - Ecological and socio-demographic differences in maternal care services in Nepal. AB - Background. Nepal is set to achieve MDG-5 goals by end of 2015. However, maternal health parameters will remain way below those of developed countries. This study was conducted to assess the factors contributing to utilization of ANC and safe delivery services with the aim of furthering overall maternal health parameters in Nepal. Material and Methods. Using survey data from the Nepal Demographic and Health Survey 2011, socio-economic and demographic factors associated with the utilization of ANC and safe delivery services among women aged 15-49 years who gave births during the last three years preceding the survey are examined. Data was segregated into three ecological zones: Mountain, Hill and Terai zones for univariate analyses. Data from all three zones was then pooled for univariate and multivariate logistic regression analyses of Antenatal Care and Safe Delivery services in Nepal. Results and Conclusion. The analyses show that rural place of residence is at a disadvantage in receiving ANC (OR, 0.8; 95% CI [0.7-0.9]) and ensuring safe delivery (OR, 0.6; 95% CI [0.5-0.7]). Woman's education, husband's education and wealth quintile are significant factors in ensuring ANC and safe delivery services. Further, the analyses show that Budh/Muslim/Kirat/Christians are at a significant disadvantage in ensuring safe delivery (OR, 0.8; 95% CI [0.7 0.9]) as compared with Hindus. Though ecological zones lost their significance in receiving ANC, women in the Terai region are at a significant advantage in ensuring safe delivery (OR, 1.7; 95% CI [1.2-2.1]). Recommendation. Segregated targets should be set for the different ecological zones for further improvement in maternal mortality rates in Nepal. PMID- 26355430 TI - Giant moving vortex mass in thick magnetic nanodots. AB - Magnetic vortex is one of the simplest topologically non-trivial textures in condensed matter physics. It is the ground state of submicron magnetic elements (dots) of different shapes: cylindrical, square etc. So far, the vast majority of the vortex dynamics studies were focused on thin dots with thickness 5-50 nm and only uniform across the thickness vortex excitation modes were observed. Here we explore the fundamental vortex mode in relatively thick (50-100 nm) dots using broadband ferromagnetic resonance and show that dimensionality increase leads to qualitatively new excitation spectra. We demonstrate that the fundamental mode frequency cannot be explained without introducing a giant vortex mass, which is a result of the vortex distortion due to interaction with spin waves. The vortex mass depends on the system geometry and is non-local because of important role of the dipolar interaction. The mass is rather small for thin dots. However, its importance increases drastically with the dot thickness increasing. PMID- 26355431 TI - Dynamic features of apo and bound HIV-Nef protein reveal the anti-HIV dimerization inhibition mechanism. AB - The first account on the dynamic features of Nef or negative factor, a small myristoylated protein located in the cytoplasm believes to increase HIV-1 viral titer level, is reported herein. Due to its major role in HIV-1 pathogenicity, Nef protein is considered an emerging target in anti-HIV drug design and discovery process. In this study, comparative long-range all-atom molecular dynamics simulations were employed for apo and bound protein to unveil molecular mechanism of HIV-Nef dimerization and inhibition. Results clearly revealed that B9, a newly discovered Nef inhibitor, binds at the dimeric interface of Nef protein and caused significant separation between orthogonally opposed residues, namely Asp108, Leu112 and Gln104. Large differences in magnitudes were observed in the radius of gyration (~1.5 A), per-residue fluctuation (~2 A), C-alpha deviations (~2 A) which confirm a comparatively more flexible nature of apo conformation due to rapid dimeric association. Compared to the bound conformer, a more globally correlated motion in case of apo structure of HIV-Nef confirms the process of dimeric association. This clearly highlights the process of inhibition as a result of ligand binding. The difference in principal component analysis (PCA) scatter plot and per-residue mobility plot across first two normal modes further justifies the same findings. The in-depth dynamic analyses of Nef protein presented in this report would serve crucial in understanding its function and inhibition mechanisms. Information on inhibitor binding mode would also assist in designing of potential inhibitors against this important HIV target. PMID- 26355432 TI - The Effect of Adrenal Replacement Therapy on Rates of Fungal Colonization and Mortality in Critically Ill Patients Awaiting Liver Transplantation. AB - BACKGROUND: The effect of adrenal replacement therapy (ART) with hydrocortisone on critical endpoints such as infection and mortality in critically ill patients with cirrhosis remains unclear. We evaluated our indications for ART in patients with cirrhosis with clinical symptoms of adrenal insufficiency (AI), and examined the rate of peri-transplant fungal colonization and mortality associated with ART. METHODS: Seventy-eight patients with cirrhosis admitted to our institution's surgical intensive care unit (ICU) over a 4-year period met criteria for AI by vasopressor requirement and baseline cortisol levels. Outcomes included disposition at 90-days, fungal colonization, and fungal infection in the presence or absence of ART. RESULTS: In total, 56 patients received hydrocortisone (HC+) while 22 did not (HC-). The HC+ and HC- groups had comparable median Model for End-stage Liver Disease (MELD) scores (26.5 vs. 25, respectively; p=0.93), median ICU lengths of stay (23 vs. 20 days, respectively; p=0.54) and median cortisol levels (18 MUg/dL for both, p=0.87). Fungal cultures (FC) from blood, urine or bronchoalveolar lavage/sputum were positive for 44% of HC+, and 40.9% of HC- (p=0.77) had mortality rates between HC+ and HC- groups that were not significantly different (60.7% vs. 50%, respectively; p=0.39; alpha=0.05). The 90 day outcomes for HC+ vs. HC- (39.3% vs. 50% discharged, respectively; p=0.39; alpha=0.05) and those surviving to transplant (17.9% vs. 36.4%, respectively; p=0.08; alpha=0.05) were not significantly different between the two groups. CONCLUSION: In this small single-center series, we found that steroid administration for AI does not affect the rate of fungal colonization/infection or mortality. Further prospective studies are required to determine the utility of ART and factors affecting the rate of FC and mortality in these patients. PMID- 26355434 TI - Bone Marrow-Derived Stem Cells in Pathogenesis of Helicobacter Pylori-Associated Gastric Cancer. AB - Bone marrow-derived stem cells (BMSCs) are now believed to be the progenitors in the development of gastric cancer in patients with chronic infection with Helicobacter pylori. However, the mechanism of recruitment and malignant transformation of these cells has not been completely understood. Here I will discuss selected findings on how BMSCs compromise local immunity and skip local defense mechanisms in order to undergo malignant transformation. In addition, the role of C-X-C chemokine receptor type 4 through binding to its ligand stromal derived factor in migration of BMSCs in mouse model of gastric cancer will be looked at. These findings are important in understanding the pathogenesis of H. pylori-associated gastric cancer and to develop new diagnostic and therapeutic modalities. PMID- 26355433 TI - Sporadic intramedullary hemangioblastoma of the spine: a single institutional review of 21 cases. AB - INTRODUCTION: Sporadic intramedullary spinal cord hemangioblastomas are rare, vascular tumours that can present with significant neurological dysfunction. Surgical resection is the standard treatment for these lesions, and we report our institution's experience with patients who underwent surgery for sporadic intramedullary spinal cord hemangioblastomas. METHODS: We retrospectively reviewed 21 patients (14 male, 7 female) who underwent a total of 23 surgeries for sporadic intramedullary spinal cord hemangioblastoma between 1996 and 2014.We recorded demographic, operative and postoperative factors. RESULTS: The median age was 45 years (IQR: 28). All tumours were present in the cervical (13 of 21, 62%) or thoracic (nine of 21, 43%) spine (one patient had tumours in both locations). Thirteen patients (62%) also had concurrent syringomyelia spanning a median of 11 vertebral levels (IQR: 5). Total resection was achieved in all but one surgery, and no cases involved intraoperative complications. However, postoperative complications occurred after five cases. Median follow-up was 12 months (IQR: 38). Twelve patients (57%) experienced long-term dysfunction after surgery, and two patients experienced recurrence requiring a second surgery. CONCLUSIONS: Maximal safe surgical resection should be considered as a primary treatment modality for individuals with intramedullary spinal cord hemangioblastomas. PMID- 26355435 TI - Radiosurgery for Large Arteriovenous Malformations as a Single-Session or Staged Treatment. AB - BACKGROUND/OBJECTIVES: The treatment of large arteriovenous malformations (AVMs) presents a challenge and the effectiveness of radiosurgery decreases with increasing treatment volume. Here, we analyzed and compared single-session treatment for AVMs >15 cm3 with staged treatment, when the volume of a large AVM was divided into 2 or more compartments, which were subsequently treated at intervals of a few months. In the event that complete obliteration was not achieved within 3 years, repeat radiosurgery was considered. METHODS/RESULTS: Between 1993 and 2011, gamma-knife radiosurgery was performed on 50 patients with large AVMs. A total of 27 of them, with volumes ranging from 15.1 to 27 cm3 (median = 17.8), were treated in a single session, with a marginal dose ranging from 10 to 17 Gy (median = 15). Complete obliteration was achieved in 7 (26%) of these; in 14 patients the treatment was repeated after a median of 38 months. The volume of AVMs subjected to repeat treatment regressed and ranged from 6.76 to 16.4 cm3 (median = 7.7), with the marginal dose ranging from 13 to 18 Gy (median = 17); 10 patients later achieved complete obliteration at a median of 79 months after the initial treatment. Overall, 63% of patients achieved complete obliteration of AVM after treatment. Rebleeding in a latent period was recorded in 3 patients (11%) and symptomatic collateral edema in 2 (7%); 23 patients were treated using the staged method, with the interval between staged treatments usually being 6 months. Their overall AVM volume ranged from 13.2 to 46.6 cm3 (median = 23.3), the volume for a single stage ranged from 4.5 to 31.3 cm3 (median 11.7), and the marginal dose ranged from 10 to 18 Gy (median = 17). Complete obliteration was achieved in 4 (17%) of them, in 8 patients the treatment was repeated at a median of 53 months after the first treatment, and a third retreatment was performed on 2 patients 98 and 102 months, respectively, after the first treatment. The volume for repeated treatment of AVMs ranged from 0.81 to 7.7 cm3 (median = 3.3), with the marginal dose ranging from 14 to 20 Gy (median 17.5). Of all the retreated patients, 5 AVMs subsequently achieved complete obliteration. Overall, 9 patients (39%) were totally cured. Rebleeding in a latent period was observed in 1 of these patients (4.3%) and symptomatic edema in another 1 (4.3%). CONCLUSIONS: Radiosurgery of large AVMs is a valuable treatment either as a single-session or staged treatment, with a reasonable chance of cure and a low risk of complications. PMID- 26355436 TI - Suspected Acute Coronary Syndromes in Women. PMID- 26355437 TI - Systematic Investigations on the Roles of the Electron Acceptor and Neighboring Ethynylene Moiety in Porphyrins for Dye-Sensitized Solar Cells. AB - Cyanoacrylic and carboxyl groups have been developed as the most extensively used electron acceptor and anchoring group for the design of sensitizers for dye sensitized solar cells. In terms of the photoelectric conversion efficiency, each of them has been demonstrated to be superior to the other one in certain cases. Herein, to further understand the effect of these two groups on cell efficiencies, a series of porphyrin sensitizers were designed and synthesized, with the acceptors systematically varied, and the effect of the neighboring ethynylene unit was also investigated. Compared with the sensitizer XW5 which contains a carboxyphenyl anchoring moiety directly linked to the meso-position of the porphyrin framework, the separate introduction of a strongly electron withdrawing cyanoacrylic acid as the anchoring group or the insertion of an ethynylene unit can achieve broadened light absorption and IPCE response, resulting in higher Jsc and higher efficiency. Thus, compared with the efficiency of 4.77% for XW5, dyes XW1 and XW6 exhibit higher efficiencies of 7.09% and 5.92%, respectively. Simultaneous introduction of the cyanoacrylic acid and the ethynylene units into XW7 can further broaden light absorption and thus further improve the Jsc. However, XW7 exhibits the lowest Voc value, which is not only related to the floppy structure of the cyanoacrylic group but also related to the aggravated dye aggregation effect due to the extended framework. As a result, XW7 exhibits a relatively low efficiency of 5.75%. These results indicate that the combination of the ethynylene and cyanoacrylic groups is an unsuccessful approach. To address this problem, a cyano substituent was introduced to XW8 at the ortho position of the carboxyl group in the carboxyphenyl acceptor. Thus, XW8 exhibits the highest efficiency of 7.59% among these dyes. Further cosensitization of XW8 with XS3 dramatically improved the efficiency to 9.31%. PMID- 26355438 TI - Synthesis of Reactive Polymers for Acrolein Capture Using AGET ATRP. AB - Acrolein is a toxic metabolite of the anticancer agent cyclophosphamide (CP). Current strategies to mitigate acrolein toxicity are insufficient, and in this brief article, we report the synthesis of well-defined low molecular weight block copolymers using activators generated by electron transfer atom transfer radical polymerization (AGET ATRP) capable of reacting with the cytotoxic small molecule acrolein. Acrolein reactivity was introduced into the block copolymers via incorporation of either (a) aminooxy or (b) sulfhydryl groups. The cytoprotective effect of the polymers was compared to sodium 2-sulfanylethanesulfonate (mesna) the current gold standard for protection from CP urotoxicity, and we found that the polymers bearing sulfhydryl moieties demonstrated superior cytoprotective activity. PMID- 26355439 TI - Laser-Assisted Operculectomy. AB - The 10,600-nm CO2 laser is both an efficient and spatially precise photo-thermal ablation device and excellent coagulator because of the close match between its coagulation depth and the diameters of oral soft-tissue capillaries. The ablation of hyperplastic oral soft tissue with the flexible fiber waveguide 10,600-nm CO2 laser is a minimally invasive and typically suture-free surgical modality that ensures dependable treatment. It is, in many respects, superior to most of the alternative treatment options. Its excellent hemostatic abilities and the minimal damage to adjacent healthy tissues make the CO2 laser a perfect surgical tool for treating oral soft-tissue lesions, including the inflamed operculum. PMID- 26355440 TI - Adhesive Cementation of Indirect Composite Inlays and Onlays: A Literature Review. AB - The authors conducted a literature review focused on materials and techniques used in adhesive cementation for indirect composite resin restorations. It was based on English language sources and involved a search of online databases in Medline, EMBASE, Cochrane Library, Web of Science, Google Scholar, and Scopus using related topic keywords in different combinations; it was supplemented by a traditional search of peer-reviewed journals and cross-referenced with the articles accessed. The purpose of most research on adhesive systems has been to learn more about increased bond strength and simplified application methods. Adherent surface treatments before cementation are necessary to obtain high survival and success rates of indirect composite resin. Each step of the clinical and laboratory procedures can have an impact on longevity and the esthetic results of indirect restorations. Cementation seems to be the most critical step, and its long-term success relies on adherence to the clinical protocols. The authors concluded that in terms of survival rate and esthetic long-term outcomes, indirect composite resin techniques have proven to be clinically acceptable. However, the correct management of adhesive cementation protocols requires knowledge of adhesive principles and adherence to the clinical protocol in order to obtain durable bonding between tooth structure and restorative materials. PMID- 26355441 TI - Systematic Risk Management: Providing a Patient the Smile She Long Desired. AB - The patient described in this case had medical issues that increased her risk for restoration failure. She also had long been disappointed with her smile and the overall appearance of her teeth. The goal of managing risks and achieving improved quality of life with an esthetic and functional restoration involved preventive strategies, use of a transitional immediate denture, maxillary arch implants, and, finally, a fixed, detachable, implant-supported final restoration. The keys to restoring to the patient a satisfying, beautiful smile were systematically managing the risks and improving the prognoses in each of the four dental categories--periodontal, biomechanical, functional, and dentofacial. PMID- 26355442 TI - Full-Mouth Rehabilitation Using All-Ceramic Restorations. AB - The scientific and technological advancement of cosmetic dentistry has improved metal-free ceramic systems for fixed prosthodontics as well as porcelain veneers, making them an excellent treatment option for delivering superior cosmetic results. The authors present a clinical case of full-mouth rehabilitation using all-ceramic restorations with porcelain metal-free unit crowns in the maxilla, and porcelain veneers from the left inferior premolar to the right inferior premolar. Using this approach, they were able to achieve an excellent esthetic and functional result for the patient. PMID- 26355443 TI - Treatment of an Unusual Non-Tooth Related Enamel Pearl (EP) and 3 Teeth-Related EPs with Localized Periodontal Disease Without Teeth Extractions: A Case Report. AB - Enamel may be found ectopically as enamel pearls (EPs), which are frequently associated with advanced localized periodontal (LP) destruction. This study presents a case in which an unusual non-tooth-related enamel pearl and three teeth-related enamel pearls with LP disease were found and treated without teeth extractions. A 47-year-old female patient presented at the New York University College of Dentistry with four EPs, three of which were associated with periodontal pockets and/or bleeding on probing (BOP), and one of them not related to any tooth. Periodontal therapy included scaling and root planing and open flap debridement with removal of the EPs. Two pearls were histologically analyzed by polarizing microscopy and scanning electron microscope (SEM). Clinical periodontal parameters, including probing depth and BOP, were measured. All enamel found in the pearls had the same general morphologic appearance when examined by a SEM. The non-tooth-related pearl could be classified as Rodriguez Ponte "adamantinoidea" pearl. Probing depths at 3 months and 9 months after EP removal diminished considerably. Only after the treatment was there no BOP. Before treatment it was in some areas, as shown in Table 1. The LP related to the EP was resolved. The authors conclude that early recognition of enamel pearls is important in the prevention of periodontal destruction, and removal of EPs by a surgical approach as an adjunct to mechanical periodontal treatment resulted in resolution of the LP. The authors state that this is the first time an "adamantinoideas" pearl is being reported on clinically in the literature. PMID- 26355444 TI - Management of Hyposalivation and Xerostomia: Criteria for Treatment Strategies. AB - Saliva management in patients with hyposalivation is potentially complex. Future development of oral care products and treatment strategies requires attention to the biology of saliva and the best means of providing a continuum of relief for people with xerostomia--the sensation of dry mouth--and hyposalivation- documented reduction in saliva flow. Improvement in patient care requires that clinicians be aware of approaches to management, desirable qualities of methods and products, and that they seek the development of products that support the functions of saliva and promote comfort and health. In this brief review of the epidemiology of hyposalivation, the biology and functions of saliva are presented in order to guide clinical decision-making to address the needs of patients with dry mouth. PMID- 26355445 TI - Utilizing Angled O-Ball Narrow-Diameter Implants to Solve the Restorative Challenge Posed by Alveolar Resorption: A Case Report. AB - An angled narrow-diameter implant has been introduced for use in cases where the atrophic edentulous ridge is wide enough to accommodate narrow-diameter implants but the necessary implant angulations would make it impossible to fabricate an esthetically acceptable overdenture. A case is described in which such implants were placed and restored. PMID- 26355446 TI - Dendritic, Oligomeric, and Polymeric Self-Immolative Molecular Amplification. PMID- 26355447 TI - Chemotherapy coordinator. PMID- 26355448 TI - Acute oncology: a developing sub-specialty. AB - Patients with cancer frequently present to hospital as an emergency admission acutely unwell. Patients can suffer from complications of the cancer itself, or significant adverse effects/toxicities related to their cancer therapy. Alternatively, the initial presentation of the malignancy may be through a hospital admission, and the cancer can frequently be widespread and with a poorer prognosis. Patients are often admitted under general physicians, away from their comprehensive cancer care centre or oncologists. Without specialist input or staff adhering to most appropriate pathways, the management of these complicated conditions may be difficult, with patients sometimes having unnecessary and painful investigations and prolonged hospital stays. To address these issues the concept of an acute oncology service has recently evolved. This is a developing sub-specialty that aims to improve the care of cancer patients presenting acutely to hospital at a devastating time in their lives. This article will explore the literature to describe the recent development of the acute oncology model, and consider different methods for the delivery of this service. PMID- 26355449 TI - BJN Award Runner Up: Oncology Nurse of the Year. AB - To contact Michelle about setting up an acute oncology service, send her an email: Michelle.Samson@nbt.nhs.uk. PMID- 26355450 TI - World-class outcomes for cancer care. PMID- 26355451 TI - Meeting the supportive care needs of young adults with cancer. PMID- 26355452 TI - Enhanced recovery programme in robotic hysterectomy. AB - The standard care for endometrial cancer includes total hysterectomy, bilateral salpingo-oophorectomy, peritoneal washings with or without bilateral pelvic and/or paraaortic lymph node dissection/sampling with or without omental biopsy or omentectomy. The aim of this narrative review is to present the advantages of robotic surgery in combination with the enhanced recovery programme to offer better care to patients with endometrial cancer. The authors argue that a well organised service for robotic hysterectomy should be set up in all hospitals. As part of this, an enhanced recovery programme including the following elements should be implemented: patient education, preoperative carbohydrate drinks, spinal or local analgesia, goal-directed fluid therapy, early feeding and intensive early mobilisation. The enhanced recovery programme includes pre, intra and postoperative changes in patient management. A comprehensive enhanced recovery programme starting in the preoperative setting and extending through to the patient's discharge, combined with robotic approach, could lead to optimal care of patients with endometrial cancer. PMID- 26355453 TI - Delirium: a diagnostic dilemma. Part 1. AB - Effective symptom management for a patient with a palliative diagnosis can be challenging. There are some symptoms that may be more difficult to control and understand than others. Delirium, as a symptom, may well prove to be a significant challenge for all involved, leaving family and health professionals perplexed and exhausted. Understanding the predisposing factors and the manifestations may aid the health professional in the assessment and identification of this distressing symptom, facilitating more effective management and care of those who are approaching the end of life. This article attempts to address some of the challenges and offer a number of suggestions that may aid in identifying delirium in patients at the end of life, but also examines some of the dilemmas when attempting to treat delirium. PMID- 26355454 TI - A Skin Crease Preserving Modification of Open-Sky Mullerectomy for Blepharoptosis Correction. AB - PURPOSE: To report the results of skin crease preservation with a modified technique of open-sky Muller's muscle-conjunctival resection that precludes the need to reconstruct the upper eyelid skin crease with full thickness sutures. METHODS: A nonrandomized, retrospective audit of 45 eyelids of 37 consecutive patients with acquired blepharoptosis, undergoing surgical correction by a single surgeon, between November 2011 and July 2014. Surgical technique involved subtotal resection of Muller's muscle plus underlying conjunctiva, under direct visualization. The stump of Muller's muscle was then reattached to the superior tarsus with buried 7-0 Vicryl. Wound closure was achieved using interrupted buried 7-0 Vicryl, without full thickness skin crease reformation. Outcomes were evaluated according to standards recommended by the British Oculoplastic Surgery Society National Ptosis survey. These included assessment of upper margin reflex distance (MRD1), skin crease, eyelid contour and symmetry and surgical complications. RESULTS: In total, all 45 eyelids met the outcome criteria for success. The median MRD1 increased from 0 mm preoperatively (range: -2 to 2) to 3.1 mm (range: 3-5 mm) following surgery, p value < 0.01. For patients with unilateral blepharoptosis, the average postoperative eyelid height difference between right and left was 0.17 mm (range: 0-1 mm). All patients achieved good eyelid contour and symmetry and none required reoperation as assessed at final follow up following surgery (mean 77 days, range: 24-366). Skin crease was lowered and normalized in all patients with median preoperative and postoperative measurements of 12 mm and 10 mm, respectively, p value < 0.01. Two cases (4.4%) developed early asymptomatic superficial punctate keratopathy, which resolved spontaneously by 4 weeks. Nonstandardized patient experience survey achieved high scores for overall satisfaction and likelihood to recommend treatment to friends and family, with low scores for postoperative pain and swelling. CONCLUSIONS: Skin Crease Preserving modified open-sky Muller's muscle-conjunctival resection is an effective technique for correcting blepharoptosis, while normalizing the skin crease. PMID- 26355455 TI - Analysing the Unequal Effects of Positive and Negative Information on the Behaviour of Users of a Taiwanese On-Line Bulletin Board. AB - The impact of social influence causes people to adopt the behaviour of others when interacting with other individuals. The effects of social influence can be direct or indirect. Direct social influence is the result of an individual directly influencing the opinion of another, while indirect social influence is a process taking place when an individual's opinion and behaviour is affected by the availability of information about others' actions. Such indirect effect may exhibit a more significant impact in the on-line community because the internet records not only positive but also negative information, for example on-line written text comments. This study focuses on indirect social influence and examines the effect of preceding information on subsequent users' opinions by fitting statistical models to data collected from an on-line bulletin board. Specifically, the different impacts of information on approval and disapproval comments on subsequent opinions were investigated. Although in an anonymous situation where social influence is assumed to be at minimum, our results demonstrate the tendency of on-line users to adopt both positive and negative information to conform to the neighbouring trend when expressing opinions. Moreover, our results suggest unequal effects of the local approval and disapproval comments in affecting the likelihood of expressing opinions. The impact of neighbouring disapproval densities was stronger than that of neighbouring approval densities on inducing subsequent disapproval relative to approval comments. However, our results suggest no effects of global social influence on subsequent opinion expression. PMID- 26355456 TI - Investigation of the Application of miR10b and miR135b in the Identification of Semen Stains. AB - To evaluate the identification method using the microRNA markers miR10b and miR135b to distinguish semen stains from menstrual blood, peripheral blood, vaginal fluid and so on body fluid stains. The expression levels of miR10b and miR35b in semen stains and menstrual blood and so on were detected utilizing a real-time quantitative PCR technique with a specific fluorescence-labeled TaqMan probe. RNU6b was used as the internal reference gene; the difference in their expression was analyzed, and the specificity, sensitivity, and detection capability of the techniques were evaluated. The expression of miR10b and miR135b in semen stains was significantly higher than that of other body fluid stains, with a mean value of DeltaCt from-6 to-7. However, it ranged from-2 to-4 for other body fluid stains. The initial criteria for judging which semen stains can be identified were determined by analyzing the research results. When the threshold value was set to 0.04, the CT value could be detected in the target genes miR10b, miR135b and in the internal reference gene RNU6b, and CT values are<40, DeltaCT[10b-U6]<-5.5, and DeltaCT[135b-U6]<-6, respectively, and the semen stain could be identified. The expression levels of miR10b and miR135b are higher in semen with strong tissue specificity; thus, they can be used to differentiate semen stains from other body fluid stains in forensic science. PMID- 26355457 TI - Different Oceanographic Regimes in the Vicinity of the Antarctic Peninsula Reflected in Benthic Nematode Communities. AB - Marine free-living nematode communities were studied at similar depths (~500 m) at two sides of the Antarctic Peninsula, characterised by different environmental and oceanographic conditions. At the Weddell Sea side, benthic communities are influenced by cold deep-water formation and seasonal sea-ice conditions, whereas the Drake Passage side experiences milder oceanic conditions and strong dynamics of the Antarctic Circumpolar Current. This resulted in different surface primary productivity, which contrasted with observed benthic pigment patterns and varied according to the area studied: chlorophyll a concentrations (as a proxy for primary production) were high in the Weddell Sea sediments, but low in the surface waters above; this pattern was reversed in the Drake Passage. Differences between areas were largely mirrored by the nematode communities: nematode densities peaked in Weddell stations and showed deeper vertical occurrence in the sediment, associated with deeper penetration of chlorophyll a and indicative of a strong bentho-pelagic coupling. Generic composition showed some similarities across both areas, though differences in the relative contribution of certain genera were noted, together with distinct community shifts with depth in the sediment at all locations. PMID- 26355459 TI - On the Chronological Structure of the Solutrean in Southern Iberia. AB - The Solutrean techno-complex has gained particular significance over time for representing a clear demographic and techno-typological deviation from the developments occurred during the course of the Upper Paleolithic in Western Europe. Some of Solutrean's most relevant features are the diversity and techno typological characteristics of the lithic armatures. These have been recurrently used as pivotal elements in numerous Solutrean-related debates, including the chronological organization of the techno-complex across Iberia and Southwestern France. In Southern Iberia, patterns of presence and/or absence of specific point types in stratified sequences tend to validate the classical ordering of the techno-complex into Lower, Middle and Upper phases, although some evidence, namely radiocarbon determinations, have not always been corroborative. Here we present the first comprehensive analysis of the currently available radiocarbon data for the Solutrean in Southern Iberia. We use a Bayesian statistical approach from 13 stratified sequences to compare the duration, and the start and end moments of each classic Solutrean phase across sites. We conclude that, based on the current data, the traditional organization of the Solutrean cannot be unquestionably confirmed for Southern Iberia, calling into doubt the status of the classically-defined type-fossils as precise temporal markers. PMID- 26355458 TI - Cell Cycle Regulates Nuclear Stability of AID and Determines the Cellular Response to AID. AB - AID (Activation Induced Deaminase) deaminates cytosines in DNA to initiate immunoglobulin gene diversification and to reprogram CpG methylation in early development. AID is potentially highly mutagenic, and it causes genomic instability evident as translocations in B cell malignancies. Here we show that AID is cell cycle regulated. By high content screening microscopy, we demonstrate that AID undergoes nuclear degradation more slowly in G1 phase than in S or G2-M phase, and that mutations that affect regulatory phosphorylation or catalytic activity can alter AID stability and abundance. We directly test the role of cell cycle regulation by fusing AID to tags that destabilize nuclear protein outside of G1 or S-G2/M phases. We show that enforced nuclear localization of AID in G1 phase accelerates somatic hypermutation and class switch recombination, and is well-tolerated; while nuclear AID compromises viability in S-G2/M phase cells. We identify AID derivatives that accelerate somatic hypermutation with minimal impact on viability, which will be useful tools for engineering genes and proteins by iterative mutagenesis and selection. Our results further suggest that use of cell cycle tags to regulate nuclear stability may be generally applicable to studying DNA repair and to engineering the genome. PMID- 26355460 TI - Salivary Telomere Length and Lung Function in Adolescents Born Very Preterm: A Prospective Multicenter Study. AB - Preterm birth is associated with abnormal respiratory functions throughout life. The mechanisms underlying these long-term consequences are still unclear. Shortening of telomeres was associated with many conditions, such as chronic obstructive pulmonary disease. We aimed to search for an association between telomere length and lung function in adolescents born preterm. Lung function and telomere length were measured in 236 adolescents born preterm and 38 born full term from the longitudinal EPIPAGE cohort. Associations between telomere length and spirometric indices were tested in univariate and multivariate models accounting for confounding factors in the study population. Airflows were significantly lower in adolescents born preterm than controls; forced expiratory volume in one second was 12% lower in the extremely preterm born group than controls (p<0.001). Lower birth weight, bronchopulmonary dysplasia and postnatal sepsis were significantly associated with lower airflow values. Gender was the only factor that was significantly associated with telomere length. Telomere length correlated with forced expiratory flow 25-75 in the extremely preterm adolescent group in univariate and multivariate analyses (p = 0.01 and p = 0.02, respectively). We evidenced an association between telomere length and abnormal airflow in a population of adolescents born extremely preterm. There was no evident association with perinatal events. This suggests other involved factors, such as a continuing airway oxidative stress leading to persistent inflammation and altered lung function, ultimately increasing susceptibility to chronic obstructive pulmonary disease. PMID- 26355461 TI - 6-Shogaol Inhibits Breast Cancer Cells and Stem Cell-Like Spheroids by Modulation of Notch Signaling Pathway and Induction of Autophagic Cell Death. AB - Cancer stem cells (CSCs) pose a serious obstacle to cancer therapy as they can be responsible for poor prognosis and tumour relapse. In this study, we have investigated inhibitory activity of the ginger-derived compound 6-shogaol against breast cancer cells both in monolayer and in cancer-stem cell-like spheroid culture. The spheroids were generated from adherent breast cancer cells. 6 shogaol was effective in killing both breast cancer monolayer cells and spheroids at doses that were not toxic to noncancerous cells. The percentages of CD44+CD24 /low cells and the secondary sphere content were reduced drastically upon treatment with 6-shogaol confirming its action on CSCs. Treatment with 6-shogaol caused cytoplasmic vacuole formation and cleavage of microtubule associated protein Light Chain3 (LC3) in both monolayer and spheroid culture indicating that it induced autophagy. Kinetic analysis of the LC3 expression and a combination treatment with chloroquine revealed that the autophagic flux instigated cell death in 6-shogaol treated breast cancer cells in contrast to the autophagy inhibitor chloroquine. Furthermore, 6-shogaol-induced cell death got suppressed in the presence of chloroquine and a very low level of apoptosis was exhibited even after prolonged treatment of the compound, suggesting that autophagy is the major mode of cell death induced by 6-shogaol in breast cancer cells. 6-shogaol reduced the expression levels of Cleaved Notch1 and its target proteins Hes1 and Cyclin D1 in spheroids, and the reduction was further pronounced in the presence of a gamma-secretase inhibitor. Secondary sphere formation in the presence of the inhibitor was also further reduced by 6-shogaol. Together, these results indicate that the inhibitory action of 6-shogaol on spheroid growth and sustainability is conferred through gamma-secretase mediated down-regulation of Notch signaling. The efficacy of 6-shogaol in monolayer and cancer stem cell-like spheroids raise hope for its therapeutic benefit in breast cancer treatment. PMID- 26355462 TI - Role of the Environment in the Transmission of Antimicrobial Resistance to Humans: A Review. AB - To establish a possible role for the natural environment in the transmission of clinically relevant AMR bacteria to humans, a literature review was conducted to systematically collect and categorize evidence for human exposure to extended spectrum beta-lactamase-producing Enterobacteriaceae, methicillin-resistant Staphylococcus aureus, and vancomycin-resistant Enterococcus spp. in the environment. In total, 239 datasets adhered to inclusion criteria. AMR bacteria were detected at exposure-relevant sites (35/38), including recreational areas, drinking water, ambient air, and shellfish, and in fresh produce (8/16). More datasets were available for environmental compartments (139/157), including wildlife, water, soil, and air/dust. Quantitative data from exposure-relevant sites (6/35) and environmental compartments (11/139) were scarce. AMR bacteria were detected in the contamination sources (66/66) wastewater and manure, and molecular data supporting their transmission from wastewater to the environment (1/66) were found. The abundance of AMR bacteria at exposure-relevant sites suggests risk for human exposure. Of publications pertaining to both environmental and human isolates, however, only one compared isolates from samples that had a clear spatial and temporal relationship, and no direct evidence was found for transmission to humans through the environment. To what extent the environment, compared to the clinical and veterinary domains, contributes to human exposure needs to be quantified. AMR bacteria in the environment, including sites relevant for human exposure, originate from contamination sources. Intervention strategies targeted at these sources could therefore limit emission of AMR bacteria to the environment. PMID- 26355463 TI - Molecular Dynamics Simulations of Adsorption of Poly(acrylic acid) and Poly(methacrylic acid) on Dodecyltrimethylammonium Chloride Micelle in Water: Effect of Charge Density. AB - We have investigated the interaction of dodecyltrimethylammonium chloride (DoTA) micelle with weak polyelectrolytes, poly(acrylic acid) and poly(methacrylic acid). Anionic as well as un-ionized forms of the polyelectrolytes were studied. Polyelectrolyte-surfactant complexes were formed within 5-11 ns of the simulation time and were found to be stable. Association is driven purely by electrostatic interactions for anionic chains whereas dispersion interactions also play a dominant role in the case of un-ionized chains. Surfactant headgroup nitrogen atoms are in close contact with the carboxylic oxygens of the polyelectrolyte chain at a distance of 0.35 nm. In the complexes, the polyelectrolyte chains are adsorbed on to the hydrophilic micellar surface and do not penetrate into the hydrophobic core of the micelle. Polyacrylate chain shows higher affinity for complex formation with DoTA as compared to polymethacrylate chain. Anionic polyelectrolyte chains show higher interaction strength as compared to corresponding un-ionized chains. Anionic chains act as polymeric counterion in the complexes, resulting in the displacement of counterions (Na(+) and Cl(-)) into the bulk solution. Anionic chains show distinct shrinkage upon adsorption onto the micelle. Detailed information about the microscopic structure and binding characteristics of these complexes is in agreement with available experimental literature. PMID- 26355464 TI - Mortality and Causes of Death in Ulcerative Colitis: Results from 20 Years of Follow-up in the IBSEN Study. AB - BACKGROUND: The best way to obtain knowledge about the natural history, including mortality, of ulcerative colitis (UC) is to conduct a longitudinal, population based, prospective study. The aims of this study were to calculate the mortality rates and causes of death in patients with UC. METHODS: A prospective, population based, longitudinal cohort study was conducted in South-Eastern Norway. A total of 519 patients (51.4% men) with UC were included over a 4-year period. A gastroenterologist from a university hospital reviewed the clinical information of all of the patients. Mortality data were retrieved from the Cause of Death Registry and from Statistics Norway. RESULTS: No statistically significant increases in total mortality or cause-specific mortality between the patients with UC and the controls were found. CONCLUSIONS: The present 20-year population based cohort study revealed a good prognosis regarding the mortality, which partially might be explained by the patients' coverage by a generally well functioning health care system. PMID- 26355466 TI - Postoperative Complications in Pediatric Inflammatory Bowel Disease: A Population based Study. AB - BACKGROUND: We describe, in a population-based cohort, the incidence of and factors associated with postoperative complications (POCs) in pediatric-onset inflammatory bowel disease. METHODS: Using the pediatric population-based EPIMAD Cohort (1988-2004), among 692 incident inflammatory bowel disease cases, 128 patients with Crohn's disease (CD) and 25 with ulcerative colitis (UC) (22%) had undergone at least 1 major abdominal surgery at a median age of 16 years [interquartile range, Q1-Q3 = 14-17]. Factors associated with POC were assessed using Cox models. RESULTS: After a median postoperative follow-up of 8 years (3 12), 76 (49.7%) patients had experienced at least 1 POC with a total of 113 complications. The frequency of severe POC (grade >2) was similar in CD and UC (28% of all complications versus 27%, P = 0.95). A total of 64 early POCs (within 30 d of surgery) were observed in 47 patients (31%), with 33 being infectious and 31 noninfectious, higher in UC than in CD (25% of patients with CD versus 60% of patients with UC, P < 0.001). Forty-nine late POCs (>=30 d) were observed in 37 patients (24%). The occurrence of late POC was similar in UC and CD. The cumulative probability of POC was 31% (95% confidence interval, 24-39) at 1 month, 46% (38-54) at 1 year, and 48% (41-57) at 5 years. Multivariate analysis found that the UC type was the only factor associated with early POC (hazard ratio = 2.9; 95% confidence interval, 1.6-5.4). CONCLUSIONS: One-half of the children with inflammatory bowel disease had experienced at least 1 POC. Only UC relative to CD was significantly associated with an increased risk of early POC. PMID- 26355467 TI - Role of Vitamin D in Infliximab-induced Remission in Adult Patients with Crohn's Disease. AB - BACKGROUND: Vitamin D is a key immunomodulator and its deficiency is prevalent among Crohn's patients. The interaction between vitamin D and the response to infliximab induction therapy has not been previously described. METHODS: Patients with moderate-severe Crohn's disease, defined as having a modified Harvey Bradshaw index >=8, who were being induced with infliximab were recruited. Patients were divided into low and normal vitamin D groups. Patients were followed prospectively for 14 weeks for achievement of clinical remission (Harvey Bradshaw index <5). At week 14, vitamin D deficient patients were supplemented with intramuscular cholecalciferol; all patients were re-assessed at week 22. Serum cytokine levels were measured at weeks 0, 14, and 22. RESULTS: Twenty-eight patients initiating infliximab were included, with 54% of patients in the low vitamin D group. The proportion of patients in clinical remission was greater in the low vitamin D group compared with the normal vitamin D group at both week 14 (80% versus 23%, P = 0.007) and week 22 (79% versus 17%, P = 0.005). The low vitamin D group had higher baseline IL-6 levels (median, 4.4 [interquartile range, 2.0-5.7] versus 1.1 [0.8-1.7] pg/mL, P = 0.004) and lower interleukin-12 levels (0.3 [0.1-0.4] versus 0.5 [0.5-0.6] pg/mL, P = 0.006) compared with the normal vitamin D group. At week 14, IL-8 levels were significantly lower in the low vitamin D group compared with the normal vitamin D group (11.2 [9.1-13.8] versus 20.5 [17.9-37.2] pg/mL, P = 0.005). CONCLUSIONS: Crohn's patients initiating infliximab with a low vitamin D level are more likely to achieve infliximab-induced clinical remission at week 14. PMID- 26355465 TI - PNPLA3 148M Carriers with Inflammatory Bowel Diseases Have Higher Susceptibility to Hepatic Steatosis and Higher Liver Enzymes. AB - BACKGROUND: Inflammatory bowel diseases (IBD) are characterized by chronic relapsing inflammation of the gastrointestinal tract and encompass Crohn's disease and ulcerative colitis. IBD are often associated with extraintestinal manifestations affecting multiple organs including the liver. Increased levels of serum aminotransferases, possibly related to nonalcoholic fatty liver disease, constitute one of the most frequently described IBD-related liver diseases. The PNPLA3 I148M substitution is a major common genetic determinant of hepatic fat content and progression to chronic liver disease. The aim of this study was to investigate whether carriers of PNPLA3 148M allele with IBD have higher risk of liver steatosis and increase in transaminases levels. METHODS: The PNPLA3 I148M (rs738409) genotype was performed by Taqman assays in 158 individuals from Southern Italy (namely, Catanzaro cohort) and in 207 individuals from Northern Italy (namely, Milan cohort) with a definite diagnosis of IBD. Demographic and clinical data and also alanine transaminase levels were collected for both cohorts. The Catanzaro cohort underwent liver evaluation by sonography and liver stiffness and controlled attenuation parameter measurements by transient elastography. RESULTS: Here, we show for the first time that carriers of the PNPLA3 148M allele with IBD have a greater risk of hepatic steatosis (odds ratio, 2.9, and confidence interval, 1.1-7.8), higher controlled attenuation parameter values (P = 0.029), and increased circulating alanine transaminase (P = 0.035) in the Catanzaro cohort. We further confirm the higher alanine transaminase levels in the Milan cohort (P < 0.001). CONCLUSIONS: Our results show that PNPLA3 148M carriers with IBD have higher susceptibility to hepatic steatosis and liver damage. PMID- 26355468 TI - Multiyear Patterns of Serum Inflammatory Biomarkers and Risk of Colorectal Neoplasia in Patients with Ulcerative Colitis. AB - BACKGROUND: Patients with ulcerative colitis (UC) are at increased risk of colorectal neoplasia (CRN) presumably because of chronic inflammation. Data on the relationship between long-term serum inflammatory biomarkers and the development of CRN in UC are limited. METHODS: We performed a 5-year study (2009 2013) of demographic, clinical, laboratory, and treatment data of patients with UC from an inflammatory bowel disease registry in relation to the development of CRN. Disease activity was evaluated by UC activity index and by serum biomarkers such as C-reactive protein (CRP), erythrocyte sedimentation rate, hemoglobin, platelets, and albumin levels. A score based on the combination of median CRP and median albumin levels (0: both normal, 1: one of them abnormal, 2: both abnormal) was also evaluated. RESULTS: A total of 773 patients with UC (median age 46 yr, 46.4% women) were included. Fifty-five patients (7.1%) developed CRN. Patients with UC and CRN had significantly higher median CRP, erythrocyte sedimentation rate, and platelets and lower hemoglobin and albumin levels compared with those without CRN. The prevalence of a CRP-albumin score (1 or 2) was significantly higher in the CRN group (40.0% or 30.9% versus 14.2% or 6.0%, respectively, P < 0.0001). In the multivariate logistic regression analysis, CRN was associated with male gender (P = 0.01), disease duration (P = 0.04), extensive colitis (P = 0.03), concomitant primary sclerosing cholangitis (P = 0.0003), median albumin levels (P = 0.03), and an increased CRP-albumin score (score 1 or 2) (P = 0.0002). CONCLUSIONS: Long-term serum inflammatory markers including the CRP albumin score are associated with increased risk of CRN in patients with UC. PMID- 26355469 TI - The Evolving Role of Thiopurines for Inflammatory Bowel Disease. PMID- 26355470 TI - Treatment Nonadherence in Inflammatory Bowel Disease: Identification, Scope, and Management Strategies. AB - Treatment adherence is of critical importance in the management of patients with IBD. Poor adherence can lead to increased disease activity, loss of response to therapy, and increased costs of care. It has been well established that adherence to long-term therapy for chronic illnesses is extremely poor, averaging around 50% in developed countries. Measured rates of nonadherence in IBD are similar, but vary depending on the type of therapy and the population being observed. This article reviews the scientific data on treatment nonadherence in IBD. The methods commonly used to evaluate treatment adherence investigation are reviewed. The consequences and scope of treatment nonadherence are summarized. Finally, the scientific data on management strategies to address the problem of treatment nonadherence are explored. PMID- 26355471 TI - Photoresponse of double-stacked graphene to Infrared radiation. AB - We report the photoresponse of stacked graphene layers towards infrared radiation. Graphene is stacked in two configurations, namely, crossed and parallel layers. Raman analysis demonstrated a strong interaction among the stacked graphene layers. Graphene in the crossed configuration exhibited the presence of both negative and positive conductivities; however, other configurations of graphene exhibited positive conductivity only. The presence of negative photoconductivity is proposed to be due to oxygen or oxygen-related functional group absorbents that are trapped in between two monolayers of graphene and act as scattering centers for free carriers. An interesting trend is reported in differential conductivity when stacked layers are compared with multilayers and parallel-stacked graphene layers. PMID- 26355472 TI - Visualizing virus particle mobility in liquid at the nanoscale. AB - Currently, there remains a critical need to develop real-time imaging resources for life sciences. Here, we demonstrate the use of high resolution in situ imaging to observe biological complexes in liquid at the nanoscale. Using a model virus system, we produced the first time-resolved videos of individual biological complexes moving in solution within an electron microscope. PMID- 26355473 TI - Determinants of between-year burrow re-occupation in a colony of the European bee eater Merops apiaster. AB - Re-occupation of existing nesting burrows in the European bee-eater Merops apiaster has only rarely - and if so mostly anecdotically - been documented in the literature record, although such behavior would substantially save time and energy. In this study, we quantify burrow re-occupation in a German colony over a period of eleven years and identify ecological variables determining reuse probability. Of 179 recorded broods, 54% took place in a reused burrow and the overall probability that one of 75 individually recognized burrows would be reused in a given subsequent year was estimated as 26.4%. This indicates that between-year burrow reuse is a common behavior in the study colony which contrasts with findings from studies in other colonies. Furthermore, burrow re occupation probability declined highly significantly with increasing age of the breeding wall. Statistical separation of within- and between-burrow effects of the age of the breeding wall revealed that a decline in re-occupation probability with individual burrow age was responsible for this and not a selective disappearance of burrows with high re-occupation probability over time. Limited duty cycles of individual burrows may be caused by accumulating detritus or decreasing stability with increasing burrow age. Alternatively, burrow fidelity may presuppose pair fidelity which may also explain the observed restricted burrow reuse duty cycles. A consequent next step would be to extend our within colony approach to other colonies and compare the ecological circumstances under which bee-eaters reuse breeding burrows. PMID- 26355474 TI - Transgenic Zebrafish Expressing mCherry in the Mitochondria of Dopaminergic Neurons. AB - Genetic mutations and environmental toxins are known to affect mitochondrial health and have been implicated in the progressive degeneration of dopaminergic neurons in Parkinson's disease. To visualize mitochondria in dopaminergic neurons of live zebrafish, we used the regulatory elements of the dopamine transporter (dat) gene to target a reporter, mCherry, after fusion with the mitochondrial localizing signal (MLS) of Tom20. Immunoblot analysis of mitochondrial and cytosolic fractions from Tg(dat:tom20 MLS-mCherry) larvae shows that mCherry is efficiently targeted to the mitochondria. Confocal imaging of live fish was carried out from 1 day postfertilization (dpf) to 9 dpf. We also colocalized dat mRNA expression with the mCherry protein in the olfactory bulb (OB), subpallium (SP), pretectum (Pr), diencephalic clusters 2 and 3 (DC2/3), caudal hypothalamus (Hc), locus coeruleus (LC), anterior preoptic area (POa), retinal amacrine cells (RAC), caudal hypothalamus (Hc), and preoptic area (PO). Treating Tg(dat:tom20 MLS-mCherry) larvae with the dopaminergic neurotoxin MPTP (1-Methyl-4-phenyl 1,2,3,6-tetrahydropyridine) at 2 or 3 dpf resulted in a decrease in mCherry fluorescence in the pretectum, olfactory bulb, subpallium, diencephalic clusters 2 and 3, and the caudal hypothalamus. Labeling of mitochondria in nigrostriatal dopaminergic neurons of zebrafish could allow their visualization in vivo following genetic or pharmacological manipulations. PMID- 26355476 TI - [Citizen partners for mental health]. PMID- 26355475 TI - Crack Propagation Versus Fiber Alignment in Collagen Gels: Experiments and Multiscale Simulation. AB - It is well known that the organization of the fibers constituting a collagenous tissue can affect its failure behavior. Less clear is how that effect can be described computationally so as to predict the failure of a native or engineered tissue under the complex loading conditions that can occur in vivo. Toward the goal of a general predictive strategy, we applied our multiscale model of collagen gel mechanics to the failure of a double-notched gel under tension, comparing the results for aligned and isotropic samples. In both computational and laboratory experiments, we found that the aligned gels were more likely to fail by connecting the two notches than the isotropic gels. For example, when the initial notches were 30% of the sample width (normalized tip-to-edge distance = 0.7), the normalized tip-to-tip distance at which the transition occurred from between-notch failure to across-sample failure shifted from 0.6 to 1.0. When the model predictions for the type of failure event (between the two notches versus across the sample width) were compared to the experimental results, the two were found to be strongly covariant by Fisher's exact test (p < 0.05) for both the aligned and isotropic gels with no fitting parameters. Although the double-notch system is idealized, and the collagen gel system is simpler than a true tissue, it presents a simple model system for studying failure of anisotropic tissues in a controlled setting. The success of the computational model suggests that the multiscale approach, in which the structural complexity is incorporated via changes in the model networks rather than via changes to a constitutive equation, has the potential to predict tissue failure under a wide range of conditions. PMID- 26355477 TI - [At the very roots of psychiatry as a new medical specialty: the Pinel-Pussin partnership]. AB - OBJECTIVES: Moral treatment is a psychological approach that contrasted sharply with a treatment of constraint, beatings, immersion in cold water, diet, or repeated heavy bleeding. In response to the violent treatment that was common in asylums of late 18th century, Philippe Pinel conceived a 'medical moral treatment'. This paper considers the roots of the recovery paradigm in the pioneering work of Philippe Pinel and Jean-Baptiste Pussin. The aim is to discuss the early 19th century moral treatment to identify some key principles that can also inspire citizenship-oriented mental health care, but we also suggest that a simple equating of citizenship-oriented practice with moral treatment overlooks some of the central aspects of the recovery paradigm. METHODS: One of the main sources for this discussion is Pinel's 'Memoir on madness' (Pinel, 1794), offered for the first time to the English-speaking reader by Dora Weiner. This analysis also draws on the 'Observations of Citizen Pussin' that Pinel asked him to write for both of them to articulate fully several of the key principles of their humanistic approach. RESULTS: Looking back on the humanistic principles that were at the core of the pioneering work of Philippe Pinel and Jean-Baptiste Pussin, we suggest that the 'moral treatment' they were advocating, more than 200 years ago, was in some ways based on a genuine patient partnership, especially on peer support. The contemporary recovery movement, that might also be centered on the full exercise of citizenship, and the older 'moral treatment' have in common that they both insist that people with mental illness be treated with dignity and respect. However, while the 'moral treatment' was taking place within the asylum, the goal of citizenship-oriented mental health care is one of a life in the community for everyone. We suggest, nevertheless, that Pinel and Pussin have formulated ideas probably so forward thinking that we are just beginning to understand and try to apply them to our post-asylum practices. CONCLUSION: Pinel's philosophy of psychiatry both undergirded moral treatment and can be useful in shaping contemporary patient-centered and citizenship-oriented practice. The insights and lessons offered by Pinel and Pussin are far from being limited to the place and time of their creation. Recent advances in mental health care have been based on insights identical to those of Pinel and Pussin regarding the episodic nature of the illness, the rarity of the illness becoming all encompassing, the reality of recovery, and the valuable roles that employment and peer mentoring can play in promoting it. We have now seen in the two hundred years that followed the publication of Pinel's Treatise the failures of asylums to provide moral treatment to persons with mental illnesse. In contrast, citizenship-oriented care stresses the importance of self-determination and the active role of the person in recovering a sense of efficacy and agency as a foundation for full citizenship for all. PMID- 26355479 TI - [Sharing experiential knowledge: Focus on the contribution of patient partners in nursing education]. AB - OBJECTIVE: This paper aims to identify the main scientific literature on patient involvement in the education of health professionals. METHODS: A literature review with keywords ''patient partner' OR 'service user' AND 'education'' in the CINAHL database identified 26 articles related to the involvement of patient partners in the training and education of health professionals. RESULTS: The presence of patient partners is positively assessed. Teachers would be able to humanize and to nuance theoretical concepts by presenting people living with a mental health problem. Students have new skills, change their attitude positively by being more aware of the factors of stigmatization in mental health and their perspective on the patient would broaden by taking in consideration the health in its entirety. Finally, patient partners, by their unveiling, would feel the therapeutic effects, a sense of pride to be recognized as peers and would exercise a civic contribution by participating in the training of health professionals. However, the literature does not allow these assertions to be evidence-based. CONCLUSION: Some challenges remain for genuine involvement of patients beginning with their integration at every levels of development in training and education programs and a better balance between scientific knowledge and experiential knowledge. PMID- 26355478 TI - [Perspective of peer helpers regarding their experience animating a self treatment program for panic disorders]. AB - OBJECTIVE: Support groups can help to reach individuals with anxiety disorders who are not or are only partly obtaining health services. The present study is based on a program that involves peer helpers as animators of a self-treatment group (Zero-ATAQ). Their perspective has been documented in order to identify the aspects of the program which can be improved. METHODS: Eleven peer helpers led the 12 sessions of the program, which was dispensed in four regions of Quebec for 32 persons having panic disorders with agoraphobia. The perspectives of ten peer animators were documented based on a semi-structured interview that took place at the end of the program, and a focus group that was held over six months later with peer animators from each of the groups. Their comments were transcribed and a thematic content analysis was conducted. RESULTS: All of the peer helper animators reported that they enjoyed participating in the program, that they appreciated being able to help others having an anxiety disorder, and that the program helped them in their role as animators of these types of activities. Nearly all of the peer helpers emphasized the importance of being able to count on the supervision of a professional when needed. CONCLUSION: This study revealed (1) the feasibility of implementing a program of this kind in partnership with peers, (2) the qualifications necessary to lead this type of program, (3) the requirements in terms of training and available material, and (4) the importance of supervision. PMID- 26355480 TI - [The other side of the fence. When the world of mental health and street meet research]. AB - Considering the patient as a partner or a collaborator is becoming more and more popular in the field of mental health research. Nevertheless, relational dynamics between patients and researchers and the issues raised by them aren't much studied. This article aims to open the debate from a case study: the participation of a peer worker to two research teams of a research and demonstration project in the field of mental health and homelessness. The story of his experience in the project explores how the realities that affects him--at the intersection of mental health problems, experience in the street and the world of consumption--have an impact on his relationships with his colleagues. Conversely, his working conditions seem to negatively affect him and produce a certain loss of identity leading him, among other things, to leave the project. The analysis suggests that conflicts that arise between the peer and his colleagues reflect hierarchies between social status and legitimate knowledge (or that needs to be recognized as valid) in the field of research. PMID- 26355481 TI - [Public Participation and Mental Health: the contrasted and unfinished response of mental health users]. AB - OBJECTIVES: The objective of this article is show the way that mental health users in Quebec responded to the last Mental Health Action Plan Directive (2005 2010): the strength of the links which were labelled as follows: 'The MSSS, The Health and Social Service Agencies, as well as the Centers of Health and Service Agencies must be sure to obtain the participation of mental health users (and those close to them), in all mental health and planning organizational services.' (MSSS, 2005: p.16) METHOD: The results presented in this article are based on the qualitative exploratory study conducted in the 11 regions of Quebec. In total 35 persons participated in the study, 13 service users, 11 persons coming from institutional environments (interveners and administrators) and 11 key players. RESULTS: The PASM's directive gave rise to a major mobilization of service users who drew up social groupings to engage in the participation activities. As well, it has permitted a generalization and regionalization of participation activities. However, the imprecision regarding the organization of the participants relative to the means required to implement the long-awaited results, has given rise to multiple interpretations, and therefore, to uneven results according to the regions, including the interior of the main region. CONCLUSIONS: The participation of service users will remain a principle whose effects will be contingent, as long as the ministerial willingness will not be accompanied by precise targets to reach, a planned process of rendering of accounts and adequate financing. PMID- 26355482 TI - [Experimentation of care partners program in psychiatry: the model Montreal]. AB - The approach of the partnership of care and services developed by the direction collaboration dans patient partnership (DCPP) of the Faculty of medicine of the University of Montreal, considers the patient as a full care actor, in the same way as healthcare professionals, his experientiel knowledges are recognized and the patient develops gradually his self-determination. Since 2010, in order to allow cultural changes involved with this approach, the 'Program Partners of Care' (PPC) facilitated resource patient' integration and involvement into Continuous Improvement Committees (CIC), within 29 general and specialized health care teams in 19 health and social services facilities in Quebec, among wich four teams specialized in mental health. The purpose of the article is to describe briefly this approach, to demonstrate that it is successfully applicable to mental health clienteles, under certain conditions. METHOD: The evaluation of this approach arises from quantitative data of self-adminitered questionnaires by the participants of continuous Improvement Commettes, as well as a reflexive approach of the participants and the members of the DCPP to understand the processes and the implemented services. The results reveal that the objectives of transformation selected through the specialized mental health CIC refer to welcoming process in the facilities, to the period of transition from a facilities service to another one, to the patient involvement in their own Interdisciplinary Plan (IIP). Among the faciliting factors for patients' participation in thse CIC: the caregivers and managers' adaptability to adjust to a patient's pace; the identification to the best communication mechanisms to get in touch with them; faciliting discussion in small working group; an existing trust relationship with the members of the CIC; the support of the resource patients between them as well as support by coach patient of the DCPP. The members of the CIC develop a sense of pride, an energy, a new motivation and a group cohesion. The patient develop a sens of belonging to the team, they experience a higher self-esteem as well as developping a sens of usefulness, by contributing to the improvement of specialized mental health facilities. Giving back, as well as participing in the better quality of services fot the benefit of other patients make a whole lot of sense for them, this process even sometimes allows their full revovrey. In conclusion, the report reveals the applicicability of this approach in the field of the mental health. It il all the more attainable when the winning conditions as the closeness of the managers specialized in the domain, the choice of significant targets of continuous improvement for the patients are taken into account. PMID- 26355483 TI - [Issues, dilemmas and managerial strategies of potential ethical risks associated with the implementation of patient partnership practices in psychiatry: a case study]. AB - OBJECTIVE: In terms of health and social services, the territory of the province of Quebec is covered by four large 'integrated university health networks,' which are involved in the coordination of care delivery and medical training. The francophone components of the public mental health system for Montreal are thus primarily linked to the Integrated University Health Network of University of Montreal. In 2010, the Faculty of Medicine of the University of Montreal has included in its development strategy a firm commitment to the development and implementation of the 'patient partner expertise' in research, training and care in order to make this expertise no less than the brand of the Faculty. This commitment applies to all medical specialties that are taught at University of Montreal, including in psychiatry. More recently, the Institut universitaire en sante mentale de Montreal (IUSMM) has endorsed a new clinical vision that promotes full citizenship, which implies that service users and carers are considered as full partners with a specific expertise to be fully deployed. The objective of this paper is to examine, from an ethical point of view, the challenges that may be associated with involving such lay persons in various levels of mental health care planning and delivery, and in research. METHODS: This study is mainly based on a review of the institutional processes that are in place at the IUSMM to promote service users' participation in care planning and delivery, and in research. The focus is on the practicalities and conditions for the exercise of such an active participation, as some questions and concerns emerged through a series of interviews with different stakeholders. These issues are addressed and discussed through the lenses of the ethical values that were formalized at IUSMM. RESULTS: Despite a firm institutional commitment at IUSMM to implement its new citizenship-oriented clinical vision through greater service users' involvement, little is known about the possible negative impacts of their participation, on themselves and for regular employees. There is a consensus on the symbolic value of recognizing the potential of service users as contributors, as a peer workers or peer research assistants. This is an historic advance compared to a time when they were considered only as more or less passive recipients of services or as a simple research subjects. Some risk factors were nonetheless identified: isolation, emotional fatigue, possible relapse, insecurity, sometimes tensed relations with health or research professionals and misunderstanding. In organizational terms, among the pitfalls, the study highlighted the need for more cautious preparatory steps, guidance and support for service users and for professionals as well, and the importance of a global and integrated governance strategy. CONCLUSION: This study points to three main recommendations to better anticipate and manage possible risks associated with more or less improvised service users' active participation, as lay persons, in complex planning and service delivery and in research. The first would be directed towards professionals for them to reflect on the quality of the doctor patient relationship in their facility as to see how service users can help to improve this relationship, but among a variety of stakeholders and without being the sole responsible for such an improvement, or for the lack of improvement thereof. The second recommendation would propose to draw an objective evaluative assessment of participatory approaches at the organizational level, promoting a real return of experience and in light of the issues raised by these practices. The third would recommend an update of the organizational ethical values when introducing practices that change the current paradigms of the provision of care and services and of research. PMID- 26355484 TI - [Personalisation in mental health: a promising way]. AB - OBJECTIVES: To demonstrate the pertinence of putting personalisation at the heart of mental health services. METHODS: Review of litterature of personalisation research and intervention in the United Kingdom, the country where the personalisation is one of the key themes of the health and social services reform agenda. RESULTS: Presentation of the key challenges in the personalisation agenda and also of web tool directly inspired by research and practices in the UK. CONCLUSION: We think that individuals want to be treated as citizens that want control and choice over their destiny. PMID- 26355485 TI - [Deliberative devices in mental health and democratization peer exchanges: the case of a user's assembly of a psychosocial care center in Brazil]. AB - Several mental health public networks in Brazil focus on the participation of a plurality of actors in different collective methods of analysis and co-management of services in order to ensure improved efficiency and greater democratization of social relations. It is clear that the analysis of the effectiveness of these collectives is often done at the expense of the social relations of power they help produce. In other words, it is as if the participatory nature of the devices immediately ensure their democratic potential and their positive impact on the recovery of the users involved.Research is presented that seeks to understand the point of view of the actors involved and to determine whether or not collective spaces for the organization of mental health services contribute to the democratization of social relations that is, the construction of individual and collective capacities for debate, decision and public action. What and how people living with serious mental disorders are protagonists in the design of service and in the struggle for quality public services and how this is involved in their recovery? The research is drawn from an organizational ethnography carried out over nearly one year in Campinas, Brazil in 2012. The research focuses on a case study in a psychosocial care center (CAPS) housing for people living with serious mental disorders. To consolidate the internal validity of the case study, three collecting data techniques were applied: the shadowing over 17 institutionalize methods or devices involved in the organization of services of the CAPS, analysis of documents and forty-seven personal interviews with users, managers and workers. This article focuses on the data from the observation of one of these devices deliberation involving users, the user's assembly, as well as interviews with 15 of these participants. The results highlight how peer exchanges, emerging in the assembly of users and the convivencia space lead to collective mobilization to improve services, social and political involvement, mutual help and to complicity and friendship. These exchanges contribute in fact to the emergence of informal peers support based on affect and critical debate. It is not the assembly of the users, but the circulation of peers, at different times of their institutional courses, in various open spaces that trigger the emergence of exchange slowly building the ongoing process of democratization. In conclusion, such observations expose the importance of creating free open space where peers at different times in their recovery process can circulate and talk together. This circulation tends to encourage informal pair support, friendship and political involvement from the time it is deployed in a plurality of open common areas; that is to say, areas where there is room for spontaneity and for the expression of affects among peers. PMID- 26355486 TI - [Encounters between peer workers and users of psychiatry in France: general characteristics and effects of the device on the representations of users. Part 1]. AB - OBJECTIVE: This series of two parent papers describes, as part of an experimental program in France, the meetings that took place between consumers of psychiatric services and peer mentors. We report on the shape, style and characteristics of these interactions. Some of their effects are also reported. The peer mentors are hospital employees who are hired through renewable contracts or, for some, on permanent contracts. The program was led by the World Health Organization Collaborating Centre for Mental Health for France, with the intention, beyond the creation of a 'new profession,' of transforming current practices and representations of public psychiatry teams towards recovery. The first paper discusses the general characteristics of the consumer/peer mentor meetings and the effects of this mechanism on the representations of the consumers about mental illness and more broadly about the health care system. The second paper reports on the therapeutic effects of these meetings. Some limitations and pitfalls are highlighted. METHODS: The program under study involved the hiring of (ex-) consumers of psychiatric services (n=29). These peer mentors are individuals 'who have had, or still have psychiatric disorders, and have experienced a process of recovery.' They were deployed in public psychiatric services after having been trainees for a year and having pursued a training of eight weeks, in parallel, that led to a peer mentor university degree. Our sample is mainly composed of patients who met at least once with a peer mentor, and who were recruited during the field survey in the sites (in-hospital, outpatient or in urban settings). We approached and spoke to patients who were likely to agree to be interviewed to share their experience and thoughts. They had to sign consent forms and thus they were told that we were working on this experimental program on peer mentors with a qualitative and inductive approach. The empirical data that is reported here comes from a qualitative sociological investigation that accompanied the evaluation of the implementation of the program between 2012 and 2014. We have conducted 74 interviews with consumers. We have a significant number of observations of the meetings between peer mentors and consumers, some of which were transcribed verbatim. We were also informed by informal discussions with consumers in every service, and through direct interviews with peer mentors, as well as through in situ observations. RESULTS: We used standardized prompt questions such as: 'Did you meet X,' or 'Do you know X?' We had to introduce the terms 'peer' or 'former patient.' In effect, in interviews with study participants it appeared that this 'X' was sometimes perceived as more of a nurse, and that they were not aware that this person was a 'peer mentor' or a former patient. The insistent style of some questions and the context of what could appear to be a formal assessment of a person's work might explain why study participants seemed inclined to give positive comments. A bias was also possible when study participants were recruited and 'prepared' by the treatment team for the interview. Despite these limitations, we can highlight the quality of the data. CONCLUSION: By the end of the experiment, 15 peer mentors were able to find and make their place in various services, despite important differences between situations with regards to their position in the institution, their degree of autonomy and responsibility, their working arrangements with other professionals, and their actual work. However, we were able to identify common determinants: the voluntary nature of the meetings; less normativity on behavior; the supply of time and availability; a distant relation to medical drugs; a blurring of boundaries between private and professional life; specific management of distance and familiarity. Concerning representations of illness and care, we found that the peer mentors actively contribute to disseminate a vision of recovery based on a positivist conception of personality. They also allow some criticism of other professionals and of the healthcare system. Consumers, in turn, evoke interactions based on the ease of contact, proximity and availability of peer mentors. This proximity can be linked to a form of camaraderie in the institutional context of care but can also lead consumers to see, in the peer mentor, a figure of 'hope.' PMID- 26355487 TI - [Encounters between peer workers and users of psychiatry in France: therapeutic effects, limits and pitfalls. Part 2]. PMID- 26355488 TI - [The life path of parents and of their children presenting an autism spectrum disorder (ASD)]. AB - OBJECTIVES: This research aims to study parents' experiences (n=41) of their autistic child. in regards to different aspects of his development, such as diagnosis, health, family, interventions, child care services, school and awareness of the disorder. METHODS: In order to ensure variability in the levels of severity of the disorder, forty-one parents of persons with an Autism Spectrum Disorder (ASD) were recruited either through the Federation quebecoise de l'autisme (FQA) or through a convenience sample. Participants were asked to complete a 192-item questionnaire covering respondents' demographic information, the child's diagnosis as well as information regarding health, family, respite services, child care setting, interventions, school setting, adolescence, adulthood, individual rights and awareness of the disorder. This questionnaire was reviewed by ten doctoral students in psychology and by three ASD experts to assess the relevance, the correctness and the richness of the questions. The questionnaire was adapted accordingly and was administered to 10 parents within the framework of a qualitative study. RESULTS: This study revealed that parents' primary concerns regarding their child's development regarded language development, visual contact, isolation and motor abilities. These parents also mentioned feeling positive emotions, such as pride and joy, as well as negative emotions, such as worries about their child's future. Only a few of these families used respite services and most deemed intervention services as insufficient; about half of parents were satisfied with the services provided at school. Moreover, most of adults with ASD have always lived with at least one of their parents; some have occupations, but their salary is minimal. In terms of disorder awareness, parents mentioned that they would have preferred that their child not have the disorder in order for them to live an easier life. CONCLUSION: Data obtained from this study serves to provide a better comprehension parents' experiences, which can contribute to adapting the services for families of children living with ASD. In addition, an increase in public funding for intervention and respite services is recommended as it was considered insufficient. PMID- 26355489 TI - [Online Activities to Support Networking in Mental Health Practices in Quebec]. AB - OBJECTIVES: To support knowledge application of evidence-based practices in mental health rehabilitation in Quebec, the Centre for Studies on Rehabilitation, Recovery and Social Inclusion (CERRIS--www.cerrisweb.com) has set up a community of practice and has organized online activities. In this article, the authors present the community of practice (457 members to date) and the results of a three-year experience aimed at evaluating their appreciation with two online activities of dissemination and knowledge exchange: Web conference and debate blog. METHODS: The methodology used in this publication is part of a process of program evaluation. More specifically, a research mixed method was used (concurrent triangulation design). Qualitative data (from qualitative questionnaires) and quantitative data (from Google analytics -participation and attendance data) were collected in parallel and incorporated into analysis step. Forty qualitative questionnaires were completed to identify the benefits, barriers, challenges and facilitators encountered during their participation in the activity. The participants are members of the community of practice of the CERRIS and are people with mental illness, family members, practitioners, researchers, students, managers and policy makers in the field of mental health rehabilitation and come from different regions of Quebec, Canada and French speaking areas of Europe. Quantitative data on participation and attendance were collected and analyzed throughout the first three years of implementation of the CERRIS. Qualitative data from the questionnaires were analyzed following a content analysis process. Quantitative data were analyzed using Excel. RESULTS: Since September 2010, 14,061 unique visitors navigated on the CERRIS website (23,391 visits) and 2,278 people visited the blog (10,393 visits). Ninety-nine members of the community of practice attended at least one of the 13 Web conferences. Web conference allows a) access to evidence-based practices, b) networking and contact between individuals of different areas and c) access to continuing education remotely. A total of 62 members of the community of practice have actively taken part in one of the 5 debates on the blog. The activity of debate blog a) promotes egalitarian exchanges between different actors in mental health sector, b) encourages diversity of viewpoints and c) create a forum for dialogue and reduce stigma towards people with mental illnesses. For both types of Web activities, technological barriers (network security, outdated computer equipment, etc.) restrained the full participation of the participants. However, the assistance received from organizations and their openness towards new technologies has facilitated the experience of participants in both activities. CONCLUSION: Online activities as Web conference and debate blog are interesting avenues to facilitate access to knowledge and support exchanges between clinical, academic, community-based communities, people who use mental health services and their families. PMID- 26355490 TI - ['I'm worthless' and other forms of self-criticism: Current knowledge and therapeutic interventions]. AB - Self-criticism is considered as a harsh or punitive evaluation of the self. It is omnipresent in culture, in daily life as well as in psychotherapy. Self-criticism can lead to question oneself but can also open new perspectives and guide us. However, it can become excessive, rigid, and might turn out to be deleterious. This present article focuses on the concept of self-criticism in clinical psychology and psychotherapy and aims to review current knowledge about this topic. First, its definition and the reasons for its development in individuals will be presented. Second, a description of the links between self-criticism and psychopathology will be made, in particular regarding depression. Finally, the third part of this article will be dedicated to the therapeutic interventions that can reduce self-criticism. PMID- 26355491 TI - Work/Life Balance: A Tale of the Blue Collar Father and the White Collar Daughter. PMID- 26355492 TI - A comparison of the i-gel(TM) and the PRO-Breathe((r)) laryngeal mask during pressure support ventilation in children. AB - Many studies comparing the i-gel(TM) with laryngeal masks include patients in whom laryngeal mask cuff inflation pressures are higher than recommended, or involve the use of neuromuscular blocking drugs and positive pressure ventilation. We compared the i-gel with the PRO-Breathe((r)) laryngeal mask in anaesthetised, spontaneously breathing children. Two hundred patients aged up to 16 years were randomly allocated to either the i-gel or the PRO-Breathe laryngeal mask. The PRO-Breathe was inflated to an intracuff pressure of 40 cmH2 O. All patients received pressure support of 10 cmH2 O and positive end-expiratory pressure of 5 cmH2 O. Successful insertion at the first attempt was 82% for the i gel compared with 93% for the PRO-Breathe (p = 0.019). Leakage volume was significantly higher with i-gel sizes 1.5 (p = 0.015), 2 (p = 0.375), 2.5 (p = 0.021) and 3 (p = 0.003) compared with the equivalent-sized PRO-Breathe device. Device dislodgement following successful initial placement was more frequent with the i-gel (5%) compared with the PRO-Breathe laryngeal mask (0%). We conclude that the PRO-Breathe laryngeal mask is superior to the i-gel in terms of leakage volume and device dislodgement. PMID- 26355493 TI - Whole-Body MRI in Children: Current Imaging Techniques and Clinical Applications. AB - Whole-body magnetic resonance imaging (MRI) is increasingly used in children to evaluate the extent and distribution of various neoplastic and non-neoplastic diseases. Not using ionizing radiation is a major advantage of pediatric whole body MRI. Coronal and sagittal short tau inversion recovery imaging is most commonly used as the fundamental whole-body MRI protocol. Diffusion-weighted imaging and Dixon-based imaging, which has been recently incorporated into whole body MRI, are promising pulse sequences, particularly for pediatric oncology. Other pulse sequences may be added to increase diagnostic capability of whole body MRI. Of importance, the overall whole-body MRI examination time should be less than 30-60 minutes in children, regardless of the imaging protocol. Established and potentially useful clinical applications of pediatric whole-body MRI are described. PMID- 26355494 TI - Difference in fascicle behaviors between superficial and deep quadriceps muscles during isometric contractions. AB - INTRODUCTION: In this study we examined changes in fascicle length and pennation of vastus intermedius (VI) and vastus lateralis (VL) from rest to isometric contraction. METHODS: Fourteen healthy men performed submaximal (30% and 50% of maximal voluntary contraction; MVC) isometric knee extensions at 60 degrees and 110 degrees knee flexion (0 degrees = full extension). Panoramic images of VL and VI were obtained at rest and during contractions to measure fascicle length and pennation using extended field-of-view ultrasonography, after confirmation that the technique could be used reliably during sustained submaximal isometric contractions. RESULTS: The relative change in fascicle length from rest to 50% MVC was greater in VI than VL at 110 degrees (P < 0.05). Pennation increased during contraction at 60 degrees for VL (P < 0.05), but not for VI. CONCLUSION: Muscle-dependent fascicle behaviors were observed during contraction. These findings may provide a mechanistic underpinning for differences in sarcomere length changes, relative force contribution, and blood flow during contraction. PMID- 26355495 TI - Training and practice of the next generation HPB surgeon: analysis of the 2014 AHPBA residents' and fellows' symposium survey. AB - BACKGROUND: Hepato-pancreato-biliary (HPB) surgery is a complex subspecialty drawing from varied training pools, and the need for competency is rapidly growing. However, no board certification process or standardized training metrics in HPB surgery exist in the Americas. This study aims to assess the attitudes of current trainees and HPB surgeons regarding the state of training, surgical practice and the HPB surgical job market in the Americas. STUDY DESIGN: A 20 question survey was distributed to members of Americas Hepato-Pancreato-Biliary Association (AHPBA) with a valid e-mail address who attended the 2014 AHPBA. Descriptive statistics were generated for both the aggregate survey responses and by training category. RESULTS: There were 176 responses with evenly distributed training tracks; surgical oncology (44, 28%), transplant (39, 24.8%) and HPB (38, 24.2%). The remaining tracks were HPB/Complex gastrointestinal (GI) and HPB/minimally invasive surgery (MIS) (29, 16% and 7, 4%). 51.2% of respondents thought a dedicated HPB surgery fellowship would be the best way to train HPB surgeons, and 68.1% felt the optimal training period would be a 2-year clinical fellowship with research opportunities. This corresponded to the 67.5% of the practicing HPB surgeons who said they would prefer to attend an HPB fellowship for 2 years as well. Overall, most respondents indicated their ideal job description was clinical practice with the ability to engage in clinical and/or outcomes research (52.3%). CONCLUSIONS: This survey has demonstrated that HPB surgery has many training routes and practice patterns in the Americas. It highlights the need for specialized HPB surgical training and career education. This survey shows that there are many ways to train in HPB. A 2-year HPB fellowship was felt to be the best way to train to prepare for a clinically active HPB practice with clinical and outcomes research focus. PMID- 26355498 TI - Metabolism in cancer metastasis. AB - Cancer metabolism has regained substantial research interest over recent years. The focus has been mostly on the primary tumor, while metabolic adjustments during dissemination have been less extensively researched. Deadhesion impairs glucose transport and brings about an ATP deficit that leads to apoptosis. To survive, metastasizing cancer cells need to increase ATP synthesis, which involves mitochondrial activity and is accomplished in part through peroxide signaling. This change in metabolism, associated with cancer spread, is different from the Warburg effect. Therefore it is important to distinguish between the metabolic adjustments in primary tumor cells and those in disseminating tumor cells. In general, it is likely that metabolic responses to environmental cues commonly occur in cell biology. PMID- 26355497 TI - Sjogren's Syndrome Accompanied by Prolactinoma: a case report and literature review. PMID- 26355496 TI - Sex and age differences in brain-derived neurotrophic factor and vimentin in the zebra finch song system: Relationships to newly generated cells. AB - The neural song circuit is enhanced in male compared with female zebra finches due to differential rates of incorporation and survival of cells between the sexes. Two double-label immunohistochemical experiments were conducted to increase the understanding of relationships between newly generated cells (marked with bromodeoxyuridine [BrdU]) and those expressing brain-derived neurotrophic factor (BDNF) and vimentin, a marker for radial glia. The song systems of males and females were investigated at posthatching day 25 during a heightened period of sexual differentiation (following BrdU injections on days 6-10) and in adulthood (following a parallel injection paradigm). In both HVC (proper name) and the robust nucleus of the arcopallium (RA), about half of the BrdU-positive cells expressed BDNF across sexes and ages. Less than 10% of the BDNF-positive cells expressed BrdU, but this percentage was greater in juveniles than adults. Across both brain regions, more BDNF-positive cells were detected in males compared with females. In RA, the number of these cells was also greater in juveniles than adults. In HVC, the average cross-sectional area covered by the vimentin labeling was greater in males than females and in juveniles compared with adults. In RA, more vimentin was detected in juveniles than adults, and within adults it was greater in females. In juveniles only, BrdU-positive cells appeared in contact with vimentin-labeled fibers in HVC, RA, and Area X. Collectively, the results are consistent with roles of BDNF- and vimentin-labeled cells influencing sexually differentiated plasticity of the song circuit. PMID- 26355499 TI - Identification of a chemoreceptor that specifically mediates chemotaxis toward metabolizable purine derivatives. AB - Chemotaxis is an essential mechanism that enables bacteria to move toward favorable ecological niches. Escherichia coli, the historical model organism for studying chemotaxis, has five well-studied chemoreceptors. However, many bacteria with different lifestyle have more chemoreceptors, most of unknown function. Using a high throughput screening approach, we identified a chemoreceptor from Pseudomonas putida KT2440, named McpH, which specifically recognizes purine and its derivatives, adenine, guanine, xanthine, hypoxanthine and uric acid. The latter five compounds form part of the purine degradation pathway, permitting their use as sole nitrogen sources. Isothermal titration calorimetry studies show that these six compounds bind McpH-Ligand Binding Domain (LBD) with very similar affinity. In contrast, non-metabolizable purine derivatives (caffeine, theophylline, theobromine), nucleotides, nucleosides or pyrimidines are unable to bind McpH-LBD. Mutation of mcpH abolished chemotaxis toward the McpH ligands identified - a phenotype that is restored by complementation. This is the first report on bacterial chemotaxis to purine derivatives and McpH the first chemoreceptor described that responds exclusively to intermediates of a catabolic pathway, illustrating a clear link between metabolism and chemotaxis. The evolution of McpH may reflect a saprophytic lifestyle, which would have exposed the studied bacterium to high concentrations of purines produced by nucleic acid degradation. PMID- 26355500 TI - Molecular Characterization and Serology of Leptospira kirschneri (Serogroup Grippotyphosa) Isolated from Urine of a Mare Post-Abortion in Brazil. AB - A strain of Leptospira kirschneri (serogroup Grippotyphosa) was cultured from urine of a mare post-abortion in Brazil and characterized by serogrouping, multiple-locus variable-number tandem repeat analysis, PGFE, and sequencing of genes rrs and secY. Strains of L. kirschneri have apparently never been recovered from horses in tropical area, only in Europe and USA. Knowledge of local epidemiology is important to interpret genetic profiles of leptospires circulating in an area. PMID- 26355501 TI - Cell surface markers and exogenously induced PpIX in synovial mesenchymal stem cells. AB - The aim of present study was to assess the expression of surface markers and the accumulation of protoporphyrin IX in synovial mesenchymal stem cells (SMSCs). SMSC from patients with rheumatoid arthritis (RA, n = 5) and osteoarthritis (OA, n = 5-6) were characterized and their PpIX accumulation rates were evaluated by flow cytometry. The expression of the 21 out of 24 tested surface markers, related to stem-like features and aggressiveness of cells showed no statistically significant differences between RA and OA groups. However, the cells from RA group had the significantly lower levels of expression for the integrin associated protein CD47 and the grow factor receptor CD271 (P = 0.018), while the higher levels of cell membrane zinc-dependent metalloproteinase CD10 (P = 0.006), as compared to the cells from OA group. Comparison of the mean intensities of PpIX fluorescence revealed no statistically significant differences between the RA and OA groups, as well as no relation to proliferation rates or cell size, although some conspicuous distinction in PpIX accumulation was observed in certain specimens within these groups, suggesting possibilities of this method application for characterization of individual SMSC populations. CD10, CD47, and CD271 were differently expressed in RA and OA SMSC, while had no direct association with the PpIX fluorescence intensity. PMID- 26355502 TI - Coupling Graphs, Efficient Algorithms and B-Cell Epitope Prediction. AB - Coupling graphs are newly introduced in this paper to meet many application needs particularly in the field of bioinformatics. A coupling graph is a two-layer graph complex, in which each node from one layer of the graph complex has at least one connection with the nodes in the other layer, and vice versa. The coupling graph model is sufficiently powerful to capture strong and inherent associations between subgraph pairs in complicated applications. The focus of this paper is on mining algorithms of frequent coupling subgraphs and bioinformatics application. Although existing frequent subgraph mining algorithms are competent to identify frequent subgraphs from a graph database, they perform poorly on frequent coupling subgraph mining because they generate many irrelevant subgraphs. We propose a novel graph transformation technique to transform a coupling graph into a generic graph. Based on the transformed coupling graphs, existing graph mining methods are then utilized to discover frequent coupling subgraphs. We prove that the transformation is precise and complete and that the restoration is reversible. Experiments carried out on a database containing 10,511 coupling graphs show that our proposed algorithm reduces the mining time very much in comparison with the existing subgraph mining algorithms. Moreover, we demonstrate the usefulness of frequent coupling subgraphs by applying our algorithm to make accurate predictions of epitopes in antibody-antigen binding. PMID- 26355503 TI - Quantifying Significance of MHC II Residues. AB - The major histocompatibility complex (MHC), a cell-surface protein mediating immune recognition, plays important roles in the immune response system of all higher vertebrates. MHC molecules are highly polymorphic and they are grouped into serotypes according to the specificity of the response. It is a common belief that a protein sequence determines its three dimensional structure and function. Hence, the protein sequence determines the serotype. Residues play different levels of importance. In this paper, we quantify the residue significance with the available serotype information. Knowing the significance of the residues will deepen our understanding of the MHC molecules and yield us a concise representation of the molecules. In this paper we propose a linear programming-based approach to find significant residue positions as well as quantifying their significance in MHC II DR molecules. Among all the residues in MHC II DR molecules, 18 positions are of particular significance, which is consistent with the literature on MHC binding sites, and succinct pseudo sequences appear to be adequate to capture the whole sequence features. When the result is used for classification of MHC molecules with serotype assigned by WHO, a 98.4 percent prediction performance is achieved. The methods have been implemented in java (http://code.google.com/p/quassi/). PMID- 26355504 TI - Intelligent Consensus Modeling for Proline Cis-Trans Isomerization Prediction. AB - Proline cis-trans isomerization (CTI) plays a key role in the rate-determining steps of protein folding. Accurate prediction of proline CTI is of great importance for the understanding of protein folding, splicing, cell signaling, and transmembrane active transport in both the human body and animals. Our goal is to develop a state-of-the-art proline CTI predictor based on a biophysically motivated intelligent consensus modeling through the use of sequence information only (i.e., position specific scores generated by PSI-BLAST). The current computational proline CTI predictors reach about 70-73 percent Q2 accuracies and about 0.40 Matthew correlation coefficient (Mcc) through the use of sequence based evolutionary information as well as predicted protein secondary structure information. However, our approach that utilizes a novel decision tree-based consensus model with a powerful randomized-metal earning technique has achieved 86.58 percent Q2 accuracy and 0.74 Mcc, on the same proline CTI data set, which is a better result than those of any existing computational proline CTI predictors reported in the literature. PMID- 26355505 TI - Residue-Specific Side-Chain Polymorphisms via Particle Belief Propagation. AB - Protein side chains populate diverse conformational ensembles in crystals. Despite much evidence that there is widespread conformational polymorphism in protein side chains, most of the X-ray crystallography data are modeled by single conformations in the Protein Data Bank. The ability to extract or to predict these conformational polymorphisms is of crucial importance, as it facilitates deeper understanding of protein dynamics and functionality. In this paper, we describe a computational strategy capable of predicting side-chain polymorphisms. Our approach extends a particular class of algorithms for side-chain prediction by modeling the side-chain dihedral angles more appropriately as continuous rather than discrete variables. Employing a new inferential technique known as particle belief propagation, we predict residue-specific distributions that encode information about side-chain polymorphisms. Our predicted polymorphisms are in relatively close agreement with results from a state-of-the-art approach based on X-ray crystallography data, which characterizes the conformational polymorphisms of side chains using electron density information, and has successfully discovered previously unmodeled conformations. PMID- 26355506 TI - A New Unsupervised Binning Approach for Metagenomic Sequences Based on N-grams and Automatic Feature Weighting. AB - The rapid development of high-throughput technologies enables researchers to sequence the whole metagenome of a microbial community sampled directly from the environment. The assignment of these sequence reads into different species or taxonomical classes is a crucial step for metagenomic analysis, which is referred to as binning of metagenomic data. Most traditional binning methods rely on known reference genomes for accurate assignment of the sequence reads, therefore cannot classify reads from unknown species without the help of close references. To overcome this drawback, unsupervised learning based approaches have been proposed, which need not any known species' reference genome for help. In this paper, we introduce a novel unsupervised method called MCluster for binning metagenomic sequences. This method uses N-grams to extract sequence features and utilizes automatic feature weighting to improve the performance of the basic K means clustering algorithm. We evaluate MCluster on a variety of simulated data sets and a real data set, and compare it with three latest binning methods: AbundanceBin, MetaCluster 3.0, and MetaCluster 5.0. Experimental results show that MCluster achieves obviously better overall performance (F-measure) than AbundanceBin and MetaCluster 3.0 on long metagenomic reads (>=800 bp); while compared with MetaCluster 5.0, MCluster obtains a larger sensitivity, and a comparable yet more stable F-measure on short metagenomic reads (<300 bp). This suggests that MCluster can serve as a promising tool for effectively binning metagenomic sequences. PMID- 26355507 TI - Gene Name Disambiguation Using Multi-Scope Species Detection. AB - Species detection is an important topic in the text mining field. According to the importance of the research topics (e.g., species assignment to genes and document focus species detection), some studies are dedicated to an individual topic. However, no researcher to date has discussed species detection as a general problem. Therefore, we developed a multi-scope species detection model to identify the focus species for different scopes (i.e., gene mention, sentence, paragraph, and global scope of the entire article). Species assignment is one of the bottlenecks of gene name disambiguation. In our evaluation, recognizing the focus species of a gene mention in four different scopes improved the gene name disambiguation. We used the species cue words extracted from articles to estimate the relevance between an article and a species. The relevance score was calculated by our proposed entities frequency-augmented invert species frequency (EF-AISF) formula, which represents the importance of an entity to a species. We also defined a relation guide factor (RGF) to normalize the relevance score. Our method not only achieved better performance than previous methods but also can handle the articles that do not specifically mention a species. In the DECA corpus, we outperformed previous studies and obtained an accuracy of 88.22 percent. PMID- 26355508 TI - Reliable and Fast Estimation of Recombination Rates by Convergence Diagnosis and Parallel Markov Chain Monte Carlo. AB - Genetic recombination is an essential event during the process of meiosis resulting in an exchange of segments between paired chromosomes. Estimating recombination rate is crucial for understanding the process of recombination. Experimental methods are normally difficult and limited to small scale estimations. Thus statistical methods using population genetics data are important for large-scale analysis. LDhat is an extensively used statistical method using rjMCMC algorithm to predict recombination rates. Due to the complexity of rjMCMC scheme, LDhat may take a long time for large SNP data sets. In addition, rjMCMC parameters should be manually defined in the original program which directly impact results. To address these issues, we designed an improved algorithm based on LDhat implementing MCMC convergence diagnostic algorithms to automatically predict values of parameters and monitor the mixing process. Then parallel computation methods were employed to further accelerate the new program. The new algorithms have been tested on ten samples from HapMap phase 2 data set. The results were compared with previous code and showed nearly identical output. However, our new methods achieved significant acceleration proving that they are more efficient and reliable for the estimation of recombination rates. The stand alone package is freely available for download http://www.ntu.edu.sg/home/zhengjie/software/CPLDhat. PMID- 26355509 TI - Identifying Cis-Regulatory Elements and Modules Using Conditional Random Fields. AB - Accurate identification of cis-regulatory elements and their correlated modules is essential for analysis of transcriptional regulation, which is a challenging problem in computational biology. Unsupervised learning has the advantage of compensating for missing annotated data, and is thus promising to be effective to identify cis-regulatory elements and modules. We introduced a Conditional Random Fields model, referred to as CRFEM, to integrate sequence features and long-range dependency of genomic sequences such as epigenetic features to identify cis regulatory elements and modules at the same time. The proposed method is able to automatically learn model parameters with no labeled data and explicitly optimize the predictive probability of cis-regulatory elements and modules. In comparison with existing methods, our method is more accurate and can be used for genome wide studies of gene regulation. PMID- 26355510 TI - Evolution and Controllability of Cancer Networks: A Boolean Perspective. AB - Cancer forms a robust system capable of maintaining stable functioning (cell sustenance and proliferation) despite perturbations. Cancer progresses as stages over time typically with increasing aggressiveness and worsening prognosis. Characterizing these stages and identifying the genes driving transitions between them is critical to understand cancer progression and to develop effective anti cancer therapies. In this work, we propose a novel model for the 'cancer system' as a Boolean state space in which a Boolean network, built from protein interaction and gene-expression data from different stages of cancer, transits between Boolean satisfiability states by "editing" interactions and "flipping" genes. Edits reflect rewiring of the PPI network while flipping of genes reflect activation or silencing of genes between stages. We formulate a minimization problem min flip to identify these genes driving the transitions. The application of our model (called BoolSpace) on three case studies-pancreatic and breast tumours in human and post spinal-cord injury (SCI) in rats-reveals valuable insights into the phenomenon of cancer progression: (i) interactions involved in core cell-cycle and DNA-damage repair pathways are significantly rewired in tumours, indicating significant impact to key genome-stabilizing mechanisms; (ii) several of the genes flipped are serine/threonine kinases which act as biological switches, reflecting cellular switching mechanisms between stages; and (iii) different sets of genes are flipped during the initial and final stages indicating a pattern to tumour progression. Based on these results, we hypothesize that robustness of cancer partly stems from "passing of the baton" between genes at different stages-genes from different biological processes and/or cellular components are involved in different stages of tumour progression thereby allowing tumour cells to evade targeted therapy, and therefore an effective therapy should target a "cover set" of these genes. A C/C++ implementation of BoolSpace is freely available at: http://www.bioinformatics.org.au/tools-data. PMID- 26355511 TI - A Survey and Comparative Study of Statistical Tests for Identifying Differential Expression from Microarray Data. AB - DNA microarray is a powerful technology that can simultaneously determine the levels of thousands of transcripts (generated, for example, from genes/miRNAs) across different experimental conditions or tissue samples. The motto of differential expression analysis is to identify the transcripts whose expressions change significantly across different types of samples or experimental conditions. A number of statistical testing methods are available for this purpose. In this paper, we provide a comprehensive survey on different parametric and non-parametric testing methodologies for identifying differential expression from microarray data sets. The performances of the different testing methods have been compared based on some real-life miRNA and mRNA expression data sets. For validating the resulting differentially expressed miRNAs, the outcomes of each test are checked with the information available for miRNA in the standard miRNA database PhenomiR 2.0. Subsequently, we have prepared different simulated data sets of different sample sizes (from 10 to 100 per group/population) and thereafter the power of each test have been calculated individually. The comparative simulated study might lead to formulate robust and comprehensive judgements about the performance of each test in the basis of assumption of data distribution. Finally, a list of advantages and limitations of the different statistical tests has been provided, along with indications of some areas where further studies are required. PMID- 26355512 TI - A New Path Based Hybrid Measure for Gene Ontology Similarity. AB - Gene Ontology (GO) consists of a controlled vocabulary of terms, annotating a gene or gene product, structured in a directed acyclic graph. In the graph, semantic relations connect the terms, that represent the knowledge of functional description and cellular component information of gene products. GO similarity gives us a numerical representation of biological relationship between a gene set, which can be used to infer various biological facts such as protein interaction, structural similarity, gene clustering, etc. Here we introduce a new shortest path based hybrid measure of ontological similarity between two terms which combines both structure of the GO graph and information content of the terms. Here the similarity between two terms t1 and t2, referred to as GOSim(PBHM)(t1,t2), has two components; one obtained from the common ancestors of t1 and t2. The other from their remaining ancestors. The proposed path based hybrid measure does not suffer from the well-known shallow annotation problem. Its superiority with respect to some other popular measures is established for protein protein interaction prediction, correlation with gene expression and functional classification of genes in a biological pathway. Finally, the proposed measure is utilized to compute the average GO similarity score among the genes that are experimentally validated targets of some microRNAs. Results demonstrate that the targets of a given miRNA have a high degree of similarity in the biological process category of GO. PMID- 26355513 TI - CAMS-RS: Clustering Algorithm for Large-Scale Mass Spectrometry Data Using Restricted Search Space and Intelligent Random Sampling. AB - High-throughput mass spectrometers can produce massive amounts of redundant data at an astonishing rate with many of them having poor signal-to-noise (S/N) ratio. These low S/N ratio spectra may not get interpreted using conventional spectra-to database matching techniques. In this paper, we present an efficient algorithm, CAMS-RS (Clustering Algorithm for Mass Spectra using Restricted Space and Sampling) for clustering of raw mass spectrometry data. CAMS-RS utilizes a novel metric (called F-set) that exploits the temporal and spatial patterns to accurately assess similarity between two given spectra. The F-set similarity metric is independent of the retention time and allows clustering of mass spectrometry data from independent LC-MS/MS runs. A novel restricted search space strategy is devised to limit the comparisons of the number of spectra. An intelligent sampling method is executed on individual bins that allow merging of the results to make the final clusters. Our experiments, using experimentally generated data sets, show that the proposed algorithm is able to cluster spectra with high accuracy and is helpful in interpreting low S/N ratio spectra. The CAMS RS algorithm is highly scalable with increasing number of spectra and our implementation allows clustering of up to a million spectra within minutes. PMID- 26355514 TI - Constructing a Gene Team Tree in Almost O (n lg n) Time. AB - An important model of a conserved gene cluster is called the gene team model, in which a chromosome is defined to be a permutation of distinct genes and a gene team is defined to be a set of genes that appear in two or more species, with the distance between adjacent genes in the team for each chromosome always no more than a certain threshold delta. A gene team tree is a succinct way to represent all gene teams for every possible value of delta. The previous fastest algorithm for constructing a gene team tree of two chromosomes requires O(n lg n lglg n) time, which was given by Wang and Lin. Its bottleneck is a problem called the maximum-gap problem. In this paper, by presenting an improved algorithm for the maximum-gap problem, we reduce the upper bound of the gene team tree problem to O(n lg n alpha(n)). Since alpha grows extremely slowly, this result is almost as efficient as the current best upper bound, O(n lg n), for finding the gene teams of a fixed delta value. Our new algorithm is very efficient from both the theoretical and practical points of view. Wang and Lin's gene-team-tree algorithm can be extended to k chromosomes with complexity O(kn lg n lglg n). Similarly, our improved algorithm for the maximum-gap problem reduces this running time to O(kn lg n alpha(n)). In addition, it also provides new upper bounds for the gene team tree problem on general sequences, in which multiple copies of the same gene are allowed. PMID- 26355515 TI - Detecting Differentially Coexpressed Genes from Labeled Expression Data: A Brief Review. AB - We review methods for capturing differential coexpression, which can be divided into two cases by the size of gene sets: 1) two paired genes and 2) multiple genes. In the first case, two genes are positively and negatively correlated with each other under one and the other conditions, respectively. In the second case, multiple genes are coexpressed and randomly expressed under one and the other conditions, respectively. We summarize a variety of methods for the first and second cases into four and three approaches, respectively. We describe each of these approaches in detail technically, being followed by thorough comparative experiments with both synthetic and real data sets. Our experimental results imply high possibility of improving the efficiency of the current methods, particularly in the case of multiple genes, because of low performance achieved by the best methods which are relatively simple intuitive ones. PMID- 26355516 TI - DNA Copy Number Selection Using Robust Structured Sparsity-Inducing Norms. AB - Array comparative genomic hybridization (aCGH) is a newly introduced method for the detection of copy number abnormalities associated with human diseases with special focus on cancer. Specific patterns in DNA copy number variations (CNVs) can be associated with certain disease types and can facilitate prognosis and progress monitoring of the disease. Machine learning techniques have been used to model the problem of tissue typing as a classification problem. Feature selection is an important part of the classification process, because many biological features are not related to the diseases and confuse the classification tasks. Multiple feature selection methods have been proposed in the different domains where classification has been applied. In this work, we will present a new feature selection method based on structured sparsity-inducing norms to identify the informative aCGH biomarkers which can help us classify different disease subtypes. To validate the performance of the proposed method, we experimentally compare it with existing feature selection methods on four publicly available aCGH data sets. In all empirical results, the proposed sparse learning based feature selection method consistently outperforms other related approaches. More important, we carefully investigate the aCGH biomarkers selected by our method, and the biological evidences in literature strongly support our results. PMID- 26355517 TI - HIV Haplotype Inference Using a Propagating Dirichlet Process Mixture Model. AB - This paper presents a new computational technique for the identification of HIV haplotypes. HIV tends to generate many potentially drug-resistant mutants within the HIV-infected patient and being able to identify these different mutants is important for efficient drug administration. With the view of identifying the mutants, we aim at analyzing short deep sequencing data called reads. From a statistical perspective, the analysis of such data can be regarded as a nonstandard clustering problem due to missing pairwise similarity measures between non-overlapping reads. To overcome this problem we propagate a Dirichlet Process Mixture Model by sequentially updating the prior information from successive local analyses. The model is verified using both simulated and real sequencing data. PMID- 26355518 TI - Improved and Promising Identification of Human MicroRNAs by Incorporating a High Quality Negative Set. AB - MicroRNA (miRNA) plays an important role as a regulator in biological processes. Identification of (pre-) miRNAs helps in understanding regulatory processes. Machine learning methods have been designed for pre-miRNA identification. However, most of them cannot provide reliable predictive performances on independent testing data sets. We assumed this is because the training sets, especially the negative training sets, are not sufficiently representative. To generate a representative negative set, we proposed a novel negative sample selection technique, and successfully collected negative samples with improved quality. Two recent classifiers rebuilt with the proposed negative set achieved an improvement of ~6 percent in their predictive performance, which confirmed this assumption. Based on the proposed negative set, we constructed a training set, and developed an online system called miRNApre specifically for human pre miRNA identification. We showed that miRNApre achieved accuracies on updated human and non-human data sets that were 34.3 and 7.6 percent higher than those achieved by current methods. The results suggest that miRNApre is an effective tool for pre-miRNA identification. Additionally, by integrating miRNApre, we developed a miRNA mining tool, mirnaDetect, which can be applied to find potential miRNAs in genome-scale data. MirnaDetect achieved a comparable mining performance on human chromosome 19 data as other existing methods. PMID- 26355519 TI - Incorporation of Biological Pathway Knowledge in the Construction of Priors for Optimal Bayesian Classification. AB - Small samples are commonplace in genomic/proteomic classification, the result being inadequate classifier design and poor error estimation. The problem has recently been addressed by utilizing prior knowledge in the form of a prior distribution on an uncertainty class of feature-label distributions. A critical issue remains: how to incorporate biological knowledge into the prior distribution. For genomics/proteomics, the most common kind of knowledge is in the form of signaling pathways. Thus, it behooves us to find methods of transforming pathway knowledge into knowledge of the feature-label distribution governing the classification problem. In this paper, we address the problem of prior probability construction by proposing a series of optimization paradigms that utilize the incomplete prior information contained in pathways (both topological and regulatory). The optimization paradigms employ the marginal log likelihood, established using a small number of feature-label realizations (sample points) regularized with the prior pathway information about the variables. In the special case of a Normal-Wishart prior distribution on the mean and inverse covariance matrix (precision matrix) of a Gaussian distribution, these optimization problems become convex. Companion website: gsp.tamu.edu/Publications/supplementary/shahrokh13a. PMID- 26355520 TI - Local Exact Pattern Matching for Non-Fixed RNA Structures. AB - Detecting local common sequence-structure regions of RNAs is a biologically important problem. Detecting such regions allows biologists to identify functionally relevant similarities between the inspected molecules. We developed dynamic programming algorithms for finding common structure-sequence patterns between two RNAs. The RNAs are given by their sequence and a set of potential base pairs with associated probabilities. In contrast to prior work on local pattern matching of RNAs, we support the breaking of arcs. This allows us to add flexibility over matching only fixed structures; potentially matching only a similar subset of specified base pairs. We present an O(n(3)) algorithm for local exact pattern matching between two nested RNAs, and an O(n(3) log n) algorithm for one nested RNA and one bounded-unlimited RNA. In addition, an algorithm for approximate pattern matching is introduced that for two given nested RNAs and a number k, finds the maximal local pattern matching score between the two RNAs with at most k mismatches in O(n(3)k(2)) time. Finally, we present an O(n(3)) algorithm for finding the most similar subforest between two nested RNAs. PMID- 26355521 TI - Maximizing Deep Coalescence Cost. AB - The minimizing deep coalescence (MDC) problem seeks a species tree that reconciles the given gene trees with the minimum number of deep coalescence events, called deep coalescence (DC) cost. To better assess MDC species trees we investigate into a basic mathematical property of the DC cost, called the diameter. Given a gene tree, a species tree, and a leaf labeling function that assigns leaf-genes of the gene tree to a leaf-species in the species tree from which they were sampled, the DC cost describes the discordance between the trees caused by deep coalescence events. The diameter of a gene tree and a species tree is the maximum DC cost across all leaf labelings for these trees. We prove fundamental mathematical properties describing precisely these diameters for bijective and general leaf labelings, and present efficient algorithms to compute the diameters and their corresponding leaf labelings. In particular, we describe an optimal, i.e., linear time, algorithm for the bijective case. Finally, in an experimental study we demonstrate that the average diameters between a gene tree and a species tree grow significantly slower than their naive upper bounds, suggesting that our exact bounds can significantly improve on assessing DC costs when using diameters. PMID- 26355522 TI - Multiple Sequence Alignment with Hidden Markov Models Learned by Random Drift Particle Swarm Optimization. AB - Hidden Markov Models (HMMs) are powerful tools for multiple sequence alignment (MSA), which is known to be an NP-complete and important problem in bioinformatics. Learning HMMs is a difficult task, and many meta-heuristic methods, including particle swarm optimization (PSO), have been used for that. In this paper, a new variant of PSO, called the random drift particle swarm optimization (RDPSO) algorithm, is proposed to be used for HMM learning tasks in MSA problems. The proposed RDPSO algorithm, inspired by the free electron model in metal conductors in an external electric field, employs a novel set of evolution equations that can enhance the global search ability of the algorithm. Moreover, in order to further enhance the algorithmic performance of the RDPSO, we incorporate a diversity control method into the algorithm and, thus, propose an RDPSO with diversity-guided search (RDPSO-DGS). The performances of the RDPSO, RDPSO-DGS and other algorithms are tested and compared by learning HMMs for MSA on two well-known benchmark data sets. The experimental results show that the HMMs learned by the RDPSO and RDPSO-DGS are able to generate better alignments for the benchmark data sets than other most commonly used HMM learning methods, such as the Baum-Welch and other PSO algorithms. The performance comparison with well-known MSA programs, such as ClustalW and MAFFT, also shows that the proposed methods have advantages in multiple sequence alignment. PMID- 26355523 TI - Approximate k-Mer Matching Using Fuzzy Hash Maps. AB - We present a fuzzy technique for approximate k-mer matching that combines the speed of hashing with the sensitivity of dynamic programming. Our approach exploits the collision detection mechanism used by hash maps, unifying the two phases of "seed and extend" into a single operation that executes in close to O(1) average time. PMID- 26355524 TI - Erratum to "Protein Function Prediction Using Multilabel Ensemble Classification". PMID- 26355525 TI - Comparative genomic hybridization on microarray (a-CGH) in olfactory neuroblastoma: Analysis of ten cases and review of the literature. AB - Olfactory neuroblastoma is a rare tumor arising from the basal layer of the olfactory epithelium in the superior recesses of the nasal cavity. The rarity of this tumor, and the difficulties in culturing tumor cells has limited the generation of conventional cytogenetic data, whereas consistent results have been obtained by recent molecular methods. We report the results of an array-based comparative genomic hybridization analysis (a-CGH) obtained on 11 samples from 10 subjects: 8 primary and 3 relapsed tumors. In one patient, both the primary and relapsed tumors were available. Our results on chromosome imbalances highlight the highly heterogeneous presentation: six of eleven samples showed multiple numerical changes and very few structural ones, while four samples showed an opposite pattern; one sample out of eleven showed no imbalances. We did not reach firm evidence of any recurrent specific imbalances either at level of entire chromosomes or chromosome segments. A review of the literature indicates a number of recurrent gains, and losses, mostly not confirmed by our results. Gain of chromosome 19 was the only correspondence with literature data concerning an entire chromosome, and most segmental gains and losses found in our cohort of patients were different from those indicated in the literature: the only similarities concerned the gain of 20q13 and the loss of segments of chromosomes 15 and 22. PMID- 26355526 TI - Childhood diarrhoea in Danish day care centres could be associated with infant colic, low birthweight and antibiotics. AB - AIM: Diarrhoea is very common in children attending day care centres. The aim of this study was to examine certain predisposing risk factors for an association with diarrhoea, including foreign travel, treatment with antibiotics, having household pets, infant colic, bottle feeding, using a pacifier and low birthweight. METHODS: A dynamic one-year follow-up cohort study comprising 179 children from 36 day care centres was conducted from September 2009 to July 2013 in Copenhagen, Denmark. Questionnaires were sent to the children's parents or legal guardians every two months for a year, requesting information on gastrointestinal symptoms and exposure. A logistic regression was performed to identify the odds ratios of different risk factors for diarrhoea. RESULTS: The odds ratios for diarrhoea were 1.97 (0.93-4.20) for children with a history of infant colic, 1.91 (0.90-4.04) for low birthweight children and 1.45 (0.74-2.82) for children who had used antibiotics. Having a pet in the household had a possible protective effect towards diarrhoeal events, with an odds ratio of 0.47 (0.20-1.09). CONCLUSION: A history of infant colic, low birthweight, and to a lesser extent antibiotic use, possibly increased the risk of diarrhoea in Danish children in day care centres. PMID- 26355527 TI - False memories in Lewy-body disease. AB - Recently, de Boysson, Belleville, Phillips et al. (2011) found that patients with Lewy-body disease (LBD) showed significantly lower rates of false memories than healthy controls, using the Deese-Roediger-McDermott (DRM) experimental procedure. Given that this result could be explained by the practically null rate of true recognition in the LBD group (0.09), we decided to replicate the study by de Boysson et al. (2011), but including a new condition that would maximize the true recognition rate (and analyze its effect on the rate of false memories). Specifically, in a DRM experiment, we manipulated (within subjects) two study and recognition conditions: in the "immediate" condition, both the LBD patients and the control group of healthy older people received a different recognition test after each study list (containing twelve words associated with a non-presented critical word), while in the "delayed" condition (similar to the one in de Boysson et al., 2011), the participants received the entire series of study lists and then took only one recognition test. The results showed that, in both samples, the "immediate" condition produced higher corrected rates of both true and false recognition than the "delayed" condition, although they were both lower in the LBD patients, which shows that these patients are capable of encoding and recognizing the general similitude underlying information (gist memory) in the right conditions. PMID- 26355528 TI - Impact of selective alveolar decortication on bisphosphonate burdened alveolar bone during orthodontic tooth movement. AB - OBJECTIVE: To investigate the effect of Selective Alveolar Decortication (SADc) facilitated orthodontic tooth movement (OTM) on bisphosphonate burdened alveolar bone in a rodent model. DESIGN: OTM was accomplished by protraction of the maxillary right first molars. Four groups were included of which two groups were pre-treated for three months with alendronate sodium (BP+TM+SADc and BP+TM group) and two groups were given saline (TM+SADc and TM group). Selective alveolar decortication surgery was performed on day 1 of appliance insertion. OTM measurements were obtained at 0, 4, and 8 weeks using in-vivo MUCT. Tissues were analysed by histology and EPMA. RESULTS: Tooth movement of 0.39 mm and 0.75 mm in the BP+TM+SADc group at 4 and 8 weeks respectively was achieved with 113% increase in tooth movement compared to BP+TM group at 4 weeks. In comparison, SADc+TM group showed 0.63 mm and 2.1 mm of tooth movement at 4 weeks and 8 weeks respectively with only 6% increase at 4 weeks and 2% increase at 8 weeks compared to TM group. Severe interproximal and buccal bone loss around the first permanent molar in the BP+TM+SADc group was seen with MUCT imaging and histology. Animals in BP+TM+SADc group histologically showed signs of osteonecrotic bone with irregular borders, loss of osteocytes and absence of osteocytic lacunae. CONCLUSION: This study demonstrated selective alveolar decortication accelerates tooth movement in a bisphosphonate burdened alveolar bone in the short term but the potential of such an invasive injury can have adverse effects. PMID- 26355529 TI - Diabetes triggers the loss of tooth structure associated to radiographical and histological dental changes and its evolution to progressive pulp and periapical lesions in rats. AB - OBJECTIVES: The aim of this study was to evaluate the putative influence of diabetes without metabolic control in the loss of tooth structure as well as histological changes in dentin and pulp tissue in rats. DESIGN: Diabetes was induced in Wistar rats (n=25) by intravenous administration of alloxan (42 mg/kg). Diabetic and non-diabetic control rats were evaluated at 1, 3, 6, 9 and 12 months of follow-up. In order to evaluate the presence and progression of dental caries and periapical lesions, hemimandibles were removed and submitted to radiographical, histological, and morphometrical procedures. RESULTS: Dental caries were detected after radiographical and histological evaluations in diabetic group from the third month of diabetes onset, increasing gradually in frequency and severity in periods. Diabetic rats dental pulps also presented significant reduction in volume density of collagen fibers and fibroblasts at third month, parallel with a trend towards the increase in inflammatory cells volume density. Diabetic rats presented a generalized pulp tissue necrosis after 6 months of diabetes induction. Moreover, periapical lesions were not detected in control group, while these lesions were observed in all rats after 3, 6, 9, and 12 months of diabetes induction. CONCLUSIONS: Uncontrolled diabetes seems to trigger the loss of tooth structure, associated to histological dental changes and mediates its evolution to progressive severe pulp and periapical lesions in rats. Therefore, diabetes may be considered a very important risk factor regarding alterations in dental pulp, development of dental caries, and periapical lesions. PMID- 26355530 TI - Prevalence of Visible Third Molars in the United States Population: How Many Individuals Have Third Molars? AB - PURPOSE: To determine the prevalence of third molars in the US population and to report the differences in prevalence of visible third molars in the most recent National Health and Nutrition Examination Survey (NHANES) population of 2011 through 2012 by participant, jaw, and demographics. MATERIALS AND METHODS: The number of visible third molars in the NHANES data was assessed in nonclinical settings by trained, calibrated dental hygienists by decade of age beginning in the 20- to 29-year-old cohort through the 70- to 79-year-old cohort. Cross sectional analyses of third molar data were conducted by the authors from the NHANES databases of 2001 through 2002, 2009 through 2010, and 2011 through 2012 to compare data for similarity of outcomes on third molar prevalence in the US population. Outcomes on third molar prevalence also were assessed from the NHANES of 2011 through 2012 by participant, jaw, and demographics: gender, race or ethnicity (Caucasian, African American, other), and education (less than high school, high school graduate, some college, college graduate). RESULTS: Data on the mean number of third molars from NHANES of 2001 through 2002, 2009 through 2010, and 2011 through 2012 were similar. The number of visible third molars in the NHANES of 2011 through 2012 decreased progressively from a mean of 1.48 in the 20- to 29-year-old cohort to 0.81 in the 60- to 69-year-old cohort, No visible third molars were observed in 47% of the 20- to 29-year-old cohort compared with 53% in the 50- to 59-year-old cohort. Participants who were male, non-Caucasian, and had less than a high school education were more likely to have a visible third molar in all age cohorts. No data were collected by NHANES examiners to determine why third molars were absent. CONCLUSION: Third molar prevalence did not appear to differ in the US population during the first decade of the 21st century. Numbers of visible third molars, prevalent in young adults, decreased progressively through each successive age cohort. Demographic differences exist for prevalence of third molars in the US population. PMID- 26355531 TI - Structure-activity relationships for lipoprotein lipase agonists that lower plasma triglycerides in vivo. AB - The risk of cardiovascular events increases in individuals with elevated plasma triglyceride (TG) levels, therefore advocating the need for efficient TG-lowering drugs. In the blood circulation, TG levels are regulated by lipoprotein lipase (LPL), an unstable enzyme that is only active as a non-covalently associated homodimer. We recently reported on a N-phenylphthalimide derivative (1) that stabilizes LPL in vitro, and moderately lowers triglycerides in vivo (Biochem. Biophys. Res. Commun.2014, 450, 1063). Herein, we establish structure-activity relationships of 51 N-phenylphthalimide analogs of the screening hit 1. In vitro evaluation highlighted that modifications on the phthalimide moiety were not tolerated and that lipophilic substituents on the central phenyl ring were functionally essential. The substitution pattern on the central phenyl ring also proved important to stabilize LPL. However, in vitro testing demonstrated rapid degradation of the phthalimide fragment in plasma which was addressed by replacing the phthalimide scaffold with other heterocyclic fragments. The in vitro potency was retained or improved and substance 80 proved stable in plasma and efficiently lowered plasma TGs in vivo. PMID- 26355532 TI - Discovery of potent and selective cytotoxic activity of new quinazoline-ureas against TMZ-resistant glioblastoma multiforme (GBM). AB - Herein, we report new quinazoline-urea based compounds with potent cytotoxic activities against TMZ-resistant glioblastoma multiforme (GBM) cells. Low micromolar IC50 values were exhibited over a panel of three primary GBM patient derived cell cultures belonging to proneural (GBM-1), mesenchymal (GBM-2), and classical (GBM-3) subtypes. Eight compounds showed excellent selectivity indices for GBM cells comparing to a normal astrocyte cell line. In JC-1 assay, analogues 11, 12, 20, 22, and 24 exerted promising rates of mPTP opening induction towards proneural GBM subtype. Compounds 11, 20, and 24 bound to the translocator protein 18 kDa (TSPO) in submicromolar range using [(3)H] PK-11195 binding affinity assay. A homology model was built and docked models of 11, 12, 20, 22 and 24 were generated for describing their plausible binding modes in TSPO. In 3D clonogenic assay, compound 20 manifested potent tumoricidal effects on TMZ-resistant GBM cells even at submicromolar concentrations. In addition, CYP450 and hERG assays presented a safe toxicity profile of 20. Taken as a whole, this report presents compound 20 as a potent, selective and safe GBM cytotoxic agent which constitutes a promising direction against TMZ-resistant GBM. PMID- 26355533 TI - A reagent for specific recognition of cysteine in aqueous buffer and in natural milk: imaging studies, enzymatic reaction and analysis of whey protein. AB - We report a new chemodosimetric probe () for specific recognition of cysteine (Cys) in aqueous buffer and in whey protein isolated from fresh cow's milk. Using this reagent we could develop a luminescence-based methodology for estimation of Cys released from a commercially available Cys-supplement drug by aminoacylase-1 in live cells. PMID- 26355534 TI - Visual symptoms in the presentation of Creutzfeldt-Jakob disease. AB - We describe a 68-year-old man with a previous history of neurosurgical repair of a skull fracture, who presented to the ophthalmology clinic with progressive visual decline. His initial visual acuity was 6/30 in the right eye and 6/48 in the left, and over 2 weeks this progressed to hand movements in both eyes. No ocular abnormalities were identified. He was noted to be increasingly confused and a subsequent MRI showed extensive bilateral posterior cortical changes consistent with cytotoxic oedema. An electroencephalogram was suggestive of encephalopathy, particularly involving the occipital lobe. He was diagnosed with the Heidenhain variant of Creutzfeldt-Jakob disease (CJD), confirmed by a positive cerebrospinal fluid 14-3-3 protein. Classically, patients with CJD present with rapidly progressive cognitive decline, ataxia and myoclonus. However, visual symptoms are a common and perhaps underrecognised manifestation of CJD. Patients can present with isolated visual symptoms which precede cognitive decline by weeks due to predominantly occipital lobe disease. This presentation is classified as the Heidenhain variant of CJD. PMID- 26355535 TI - Controlling the physics and chemistry of binary and ternary praseodymium and cerium oxide systems. AB - Rare earth praseodymium and cerium oxides have attracted intense research interest in the last few decades, due to their intriguing chemical and physical characteristics. An understanding of the correlation between structure and properties, in particular the surface chemistry, is urgently required for their application in microelectronics, catalysis, optics and other fields. Such an understanding is, however, hampered by the complexity of rare earth oxide materials and experimental methods for their characterisation. Here, we report recent progress in studying high-quality, single crystalline, praseodymium and cerium oxide films as well as ternary alloys grown on Si(111) substrates. Using these well-defined systems and based on a systematic multi-technique surface science approach, the corresponding physical and chemical properties, such as the surface structure, the surface morphology, the bulk-surface interaction and the oxygen storage/release capability, are explored in detail. We show that specifically the crystalline structure and the oxygen stoichiometry of the oxide thin films can be well controlled by the film preparation method. This work leads to a comprehensive understanding of the properties of rare earth oxides and highlights the applications of these versatile materials. Furthermore, methanol adsorption studies are performed on binary and ternary rare earth oxide thin films, demonstrating the feasibility of employing such systems for model catalytic studies. Specifically for ceria systems, we find considerable stability against normal environmental conditions so that they can be considered as a "materials bridge" between surface science models and real catalysts. PMID- 26355536 TI - Sneezing during Micturition: A Possible Trigger of Acute Bacterial Prostatitis. AB - A perfectly well 39-year-old man sneezed during micturition and developed classic features of acute bacterial prostatitis corroborated by laboratory evidence of prostatic inflammation/infection. The prostate-specific antigen level at presentation was 9.6 ng/mL and declined to 1.23 ng/mL one month later on levofloxacin. This is the first report in the medical literature of sneezing while voiding being a possible trigger of acute bacterial prostatitis. A biologically plausible mechanism is provided. PMID- 26355537 TI - Chinese Herbal Medicine-induced Liver Injury. AB - The widespread use of Chinese herbal medicine (CHM) and the associated adverse reactions has attracted the attention of researchers and physicians. Reports have shown that several types of CHM can cause liver injury, with increasing numbers of cases reported every year. The difficulty in characterizing CHM-induced liver injury stems from clinical manifestations, diagnosis and pathogenesis. The clinical manifestations are varied, but gastrointestinal symptoms are the majority. The Council for International Organizations of Medical Sciences scale is currently the most commonly used method for assessing causality in cases of medicine-induced liver injury with excellent sensitivity, specificity and predictive validity. However, the pathogenesis of CHM-induced liver injury is not well understood. The classic view encompasses a contribution from "toxic metabolites" that either elicit an immune response or directly affect cellular biochemical processes or functions. In addition, poor quality and inappropriate clinical use of CHMs contribute to safety concerns. To ensure the safe use of CHMs and decrease the number of hepatotoxic cases, clinicians, researchers and pharmaceutical companies should share responsibility by regulating clinical use, strengthening basic toxicology research and establishing a strict quality control system. PMID- 26355538 TI - In situ patterned micro 3D liver constructs for parallel toxicology testing in a fluidic device. AB - 3D tissue models are increasingly being implemented for drug and toxicology testing. However, the creation of tissue-engineered constructs for this purpose often relies on complex biofabrication techniques that are time consuming, expensive, and difficult to scale up. Here, we describe a strategy for realizing multiple tissue constructs in a parallel microfluidic platform using an approach that is simple and can be easily scaled for high-throughput formats. Liver cells mixed with a UV-crosslinkable hydrogel solution are introduced into parallel channels of a sealed microfluidic device and photopatterned to produce stable tissue constructs in situ. The remaining uncrosslinked material is washed away, leaving the structures in place. By using a hydrogel that specifically mimics the properties of the natural extracellular matrix, we closely emulate native tissue, resulting in constructs that remain stable and functional in the device during a 7-day culture time course under recirculating media flow. As proof of principle for toxicology analysis, we expose the constructs to ethyl alcohol (0-500 mM) and show that the cell viability and the secretion of urea and albumin decrease with increasing alcohol exposure, while markers for cell damage increase. PMID- 26355540 TI - Genome analysis of quorum sensing Cedecea neteri SSMD04 leads to identification of its novel signaling synthase (cneI), cognate receptor (cneR) and an orphan receptor. AB - Cedecea neteri is a very rare human pathogen. We have isolated a strain of C. neteri SSMD04 from pickled mackerel sashimi identified using molecular and phenotypics approaches. Using the biosensor Chromobacterium violaceum CV026, we have demonstrated the presence of short chain N-acyl-homoserine lactone (AHL) type quorum sensing (QS) activity in C. neteri SSMD04. Triple quadrupole LC/MS analysis revealed that C. neteri SSMD04 produced short chain N-butyryl-homoserine lactone (C4-HSL). With the available genome information of C. neteri SSMD04, we went on to analyse and identified a pair of luxI/R homologues in this genome that share the highest similarity with croI/R homologues from Citrobacter rodentium. The AHL synthase, which we named cneI(636 bp), was found in the genome sequences of C. neteri SSMD04. At a distance of 8bp from cneI is a sequence encoding a hypothetical protein, potentially the cognate receptor, a luxR homologue which we named it as cneR. Analysis of this protein amino acid sequence reveals two signature domains, the autoinducer-binding domain and the C-terminal effector which is typical characteristic of luxR. In addition, we found that this genome harboured an orphan luxR that is most closely related to easR in Enterobacter asburiae. To our knowledge, this is the first report on the AHL production activity in C. neteri, and the discovery of its luxI/R homologues, the orphan receptor and its whole genome sequence. PMID- 26355541 TI - The Effects of Sex, Limb Dominance, and Soccer Participation on Knee Proprioception and Dynamic Postural Control. AB - CONTEXT: Both female athletes' participation in soccer and associated injuries have greatly increased in recent years. One issue is the 2-9 times greater incidence of noncontact anterior cruciate ligament (ACL) injuries in female athletes relative to male athletes in comparable sports. Several factors such as limb dominance and sporting history have been proposed to play a role in ACL incidence rates between male and female athletes. However, evidence about the effects of these factors and how they interact with sex is mixed, and thus no consensus exists. OBJECTIVE: To quantify the effects of sports participation, limb dominance, and sex on dynamic postural control and knee-joint proprioception. DESIGN: Cross-sectional study. SETTING: University research laboratory. PARTICIPANTS: 19 male soccer players, 17 female soccer players, 19 sedentary men, and 18 sedentary women. INTERVENTION: Joint-position sense was tested using reproduction of passive positioning on a Biodex isokinetic dynamometer (30 degrees , 45 degrees , and 60 degrees from 90 degrees of knee flexion). Three Star Excursion Balance Test directions were used to assess dynamic postural control. MAIN OUTCOME MEASURE: Normalized reach distance (% of leg length) in the anterior, posteromedial, and posterolateral directions on each leg quantified dynamic postural control. Average absolute error and constant error for both limbs quantified joint-position sense. RESULTS: Posteromedial reach distance was significantly better in soccer players than sedentary individuals (P = .006). Anterior reach distance was significantly better (P = .04) in sedentary individuals than soccer players. No limb-dominance or sex differences were identified for dynamic postural control, and no differences in absolute- or constant-error scores were identified. CONCLUSION: Sporting history has a direction-specific impact on dynamic postural control. Sporting history, sex, and limb dominance do not influence knee-joint proprioception when tested in an open kinetic chain using passive repositioning. PMID- 26355542 TI - Modeling of the Bacillus subtilis Bacterial Biofilm Growing on an Agar Substrate. AB - Bacterial biofilms are organized communities composed of millions of microorganisms that accumulate on almost any kinds of surfaces. In this paper, a biofilm growth model on an agar substrate is developed based on mass conservation principles, Fick's first law, and Monod's kinetic reaction, by considering nutrient diffusion between biofilm and agar substrate. Our results show biofilm growth evolution characteristics such as biofilm thickness, active biomass, and nutrient concentration in the agar substrate. We quantitatively obtain biofilm growth dependence on different parameters. We provide an alternative mathematical method to describe other kinds of biofilm growth such as multiple bacterial species biofilm and also biofilm growth on various complex substrates. PMID- 26355543 TI - Appropriate Health Care: A Surgeon's View of the Patient With Pancreatic Disease: The Paul Webster Clinical State of the Art Lecture American Pancreatic Association, November 2014. PMID- 26355544 TI - Autoimmune Pancreatitis: The Past, Present, and Future. AB - Before the immunoglobulin G4 (IgG4) era, autoimmune pancreatitis was proposed as a single clinical entity of autoimmune disease. In the IgG4 era, the following 2 subtypes have been proposed: type 1 is the pancreatic manifestation of IgG4 related disease and type 2 presents with granulocytic epithelial lesions. The characteristic features of type 1 are increased serum IgG4, lymphoplasmacytic sclerosing pancreatitis (abundant infiltration of IgG4+ plasmacytes and lymphocytes, storiform fibrosis, and obliterative phlebitis), other organ involvements (eg, sclerosing cholangitis, sclerosing sialadenitis, retroperitoneal fibrosis), and responsiveness to steroid. Diagnosis of both types can be made using the International Consensus Diagnostic Criteria. Different from type 2, approximately half of type 1 shows a relapse within 1 year after remission. Despite consensus for the initial steroid treatment, steroid maintenance and treatment for relapses are controversial. In the long term, approximately 10% of type 1 may develop chronic pancreatitis or pancreatic stone formation. It is controversial whether autoimmune pancreatitis is a risk factor for malignancy. Although the pathogenic mechanism remains unclear, multiple factors such as genetic background and abnormal immunity may be involved. Future studies should be conducted to identify more specific and novel biomarkers for each subtype, alternative treatment options for relapse, and the precise pathogenic mechanism. PMID- 26355545 TI - Continuous Regional Arterial Infusion of Protease Inhibitors for Treatment of Severe Acute Pancreatitis: Systematic Review and Meta-Analysis. AB - OBJECTIVE: We performed a systematic review and meta-analysis of observational studies and randomized controlled trials (RCTs) to assess the benefit and risk of continuous regional arterial infusion (CRAI) of protease inhibitors (CRAIpis) in patients with severe acute pancreatitis (SAP) or acute necrotizing pancreatitis (ANP). METHODS: The search was performed using the key words "pancreatitis" and "regional arterial infusion." All language studies involving adult cases of SAP or ANP, which assessed the impact of the CRAIpis, were included. RESULTS: Our analysis included 8 observational studies and 2 RCTs from 376 potentially relevant articles. With regard to the observational studies, the CRAIpi was significantly associated with decreased both mortality (odds ratio, 0.40; 95% confidential interval [CI], 0.25-0.64; P = 0.0001) and the need for urgent surgical intervention (odds ratio, 0.22; 95% CI, 0.12-0.3; P < 0.0001). In the RCTs, the application of CRAIpi tends to decrease the mortality but does not reach the significance (risk reduction, -0.12; 95% CI, -0.36-0.12; P = 0.33). CONCLUSIONS: The CRAIpi has the potential to reduce the mortality or the need for urgent surgical intervention in cases of SAP or ANP. Further, large multicenter trials are needed to refute or confirm our findings. PMID- 26355546 TI - DNA Hypermethylation as a Blood-Based Marker for Pancreatic Cancer: A Literature Review. AB - OBJECTIVES: The aim is to review genes aberrantly methylated in pancreatic cancer. This review focuses on DNA promoter hypermethylation in plasma and serum to describe the most promising genes that may be useful as minimally invasive diagnostic blood-based markers for pancreatic cancer. METHODS: A systematic search of the literature was performed using the PubMed and EMBASE databases. The following MeSH terms and free text were used: pancreatic disease, pancreatic cancer, pancreatic neoplasm, methylation, DNA hypermethylation, CG rich sequence, CpG island, cell-free DNA, blood, plasma, serum, fluids, and secretions. RESULTS: In total, 720 articles were found. Eight studies on cell-free DNA promoter hypermethylation in plasma or serum and 2 studies on hypermethylation in whole blood/leukocyte DNA from patients with pancreatic cancer were identified. The search for a hypermethylated marker in cell-free DNA is characterized by a few small studies lacking well-defined control groups. No single gene has been identified as a diagnostic marker. CONCLUSION: Because of insufficient power, none of the genes examined have the potential to work as an individual diagnostic marker, suggesting that a panel of several genes is needed. Further research is warranted before a blood-based diagnostic marker for pancreatic cancer based on promoter hypermethylation can be applied clinically. PMID- 26355547 TI - Targeting Epidermal Growth Factor Receptor-Related Signaling Pathways in Pancreatic Cancer. AB - Pancreatic cancer is aggressive, chemoresistant, and characterized by complex and poorly understood molecular biology. The epidermal growth factor receptor (EGFR) pathway is frequently activated in pancreatic cancer; therefore, it is a rational target for new treatments. However, the EGFR tyrosine kinase inhibitor erlotinib is currently the only targeted therapy to demonstrate a very modest survival benefit when added to gemcitabine in the treatment of patients with advanced pancreatic cancer. There is no molecular biomarker to predict the outcome of erlotinib treatment, although rash may be predictive of improved survival; EGFR expression does not predict the biologic activity of anti-EGFR drugs in pancreatic cancer, and no EGFR mutations are identified as enabling the selection of patients likely to benefit from treatment. Here, we review clinical studies of EGFR-targeted therapies in combination with conventional cytotoxic regimens or multitargeted strategies in advanced pancreatic cancer, as well as research directed at molecules downstream of EGFR as alternatives or adjuncts to receptor targeting. Limitations of preclinical models, patient selection, and trial design, as well as the complex mechanisms underlying resistance to EGFR-targeted agents, are discussed. Future clinical trials must incorporate translational research end points to aid patient selection and circumvent resistance to EGFR inhibitors. PMID- 26355548 TI - Japanese Clinical Guidelines for Endoscopic Treatment of Pancreatolithiasis. AB - OBJECTIVES: In addition to surgery, procedures for patients with pancreatolithiasis are developing; therefore, establishing practical guidelines for the management of pancreatolithiasis is required. METHODS: Three committees (the professional committee for asking clinical questions (CQs) and statements by Japanese endoscopists, the expert panel committee for rating statements by the modified Delphi method, and the evaluating committee by moderators) were organized. Eight endoscopists and a surgeon for pancreatolithiasis made the CQs and statements from a total of 694 reports of published literature by PubMed search (from 1983 to 2012). The expert panelists individually rated these clinical statements using a modified Delphi approach, in which a clinical statement receiving a median score greater than 7 on a 9-point scale from the panel was regarded as valid. RESULTS: The professional committee made 3, 7, and 10 CQs and statements for the concept and pathogenesis, diagnosis, and treatment, respectively. The expert panelists regarded them as valid after a 2-round modified Delphi approach. CONCLUSIONS: After evaluation by the moderators, the Japanese clinical guidelines for pancreatolithiasis were established. Further discussions and studies for international guidelines are needed. PMID- 26355549 TI - The Long-Term Impact of Autoimmune Pancreatitis on Pancreatic Function, Quality of Life, and Life Expectancy. AB - OBJECTIVE: To evaluate the long-term outcome of autoimmune pancreatitis. METHODS: Patients with at least 2 years of follow-up were included. Information was collected regarding disease characteristics, treatment outcome, diagnosed malignancies, and mortality. In addition, pancreatic function and quality of life were assessed prospectively. RESULTS: 107 patients were included (87% men, 90% with type 1), with a median follow-up of 74 (interquartile range, 49-108) months. One third was operated for suspected pancreatic cancer (32%). Most patients were (successfully) treated with steroids (83%), but relapses were common (52%), for which no risk factors could be identified. Pancreatic carcinoma was not observed.Prospective data were obtained from 64%, as 17% had died, 7% were lost to follow-up, and 13% refused to participate. After a median of 75 (interquartile range, 50-106) months, 46% still used active treatment. Exocrine and endocrine insufficiencies were highly prevalent (82% and 57%, respectively). Quality of life and survival were not impaired, as compared with a reference population. CONCLUSIONS: Despite an excellent initial treatment response, relapses are common, even in type 2, and almost half of the patients require maintenance therapy. Pancreatic insufficiency is highly prevalent, which calls for active screening. Pancreatic cancer was not observed, and quality of life and survival are not impaired. PMID- 26355550 TI - Pregnane X Receptor Expression in Human Pancreatic Adenocarcinoma: Associations With Clinicopathologic Parameters, Tumor Proliferative Capacity, Patients' Survival, and Retinoid X Receptor Expression. AB - OBJECTIVES: Pregnane X receptor (PXR) has been involved in human malignancy, either by directly affecting carcinogenesis or by inducing drug-drug interactions and chemotherapy resistance. The present study aimed to assess the clinical significance of PXR in pancreatic adenocarcinoma. METHODS: Pregnane X receptor and its heterodimers' PXR/retinoid X receptor alpha (RXR-alpha), RXR-beta, and RXR-gamma expression were assessed immunohistochemically on tumoral samples from 55 pancreatic adenocarcinoma patients and were associated with clinicopathologic parameters, tumor proliferative capacity, and patients' survival. RESULTS: Enhanced PXR expression was noted in 24 (43.6%) of 55 pancreatic adenocarcinoma cases. Pancreatic adenocarcinoma patients presenting increased histological grade of tumor differentiation showed a significant increased incidence of elevated PXR expression (P = 0.023). Enhanced PXR/RXR-beta expression was significantly associated with smaller tumor size and earlier clinical stage (P = 0.005 and P = 0.003, respectively). Elevated PXR/RXR-gamma expression was significantly associated with smaller tumor size and earlier clinical stage (P = 0.012 and P = 0.014, respectively) and borderline with the absence of lymph node metastases (P = 0.056). In addition, pancreatic adenocarcinoma patients presenting enhanced PXR/RXR-gamma expression showed marginally longer survival times compared with those with decreased expression (log-rank test, P = 0.053). CONCLUSIONS: This study supported evidence that PXR and its copartners' overexpression may be associated with favorable clinicopathologic parameters and better outcome in pancreatic adenocarcinoma. PMID- 26355551 TI - Asparagine Synthetase Expression and Phase I Study With L-Asparaginase Encapsulated in Red Blood Cells in Patients With Pancreatic Adenocarcinoma. AB - OBJECTIVES: Asparaginase encapsulated in erythrocytes (ERY-ASP) is a potentially effective drug in patients with pancreatic adenocarcinoma (PAC) with null/low asparagine synthetase (ASNS) expression. Our aims were to assess ASNS expression in PAC from a large cohort and its prognostic and/or predictive value and to conduct a phase I trial with ERY-ASP in patients with metastatic PAC. METHODS: Asparagine synthetase expression was evaluated using immunohistochemistry in resected PAC (471 patients) and in pairs of primary tumor and metastases (55 patients). Twelve patients were included in the phase I trial and received a single administration of ERY-ASP (25-150 IU/kg). RESULTS: Null/low ASNS expression was found in 79.4% of the resected PAC with a high concordance between primary tumor and metastases. Asparagine synthetase expression was significantly correlated with sex and CXCR4 expression. In the phase I trial, ERY-ASP was well tolerated by patients with metastatic PAC. No patient had DLTs, and 6 patients had at least 1 ERY-ASP causally related adverse event out of the 12 adverse events reported. CONCLUSIONS: Given the high rate of PAC with null/low ASNS expression and the good tolerability profile of ERY-ASP, ERY-ASP should be evaluated in further clinical studies in metastatic PAC. PMID- 26355552 TI - Impact of Smoking on Pancreatic Cancer Patients Receiving Current Chemotherapy. AB - OBJECTIVE: Smoking may affect pharmacokinetics of chemotherapeutic agents and hemodynamics of the smokers, thereby influencing adverse events and efficacy of chemotherapy in patients with pancreatic cancer (PC). The aim of this study was to clarify how smoking totally affected patients with PC receiving current chemotherapy. METHODS: We evaluated the impact of smoking status on the performance of chemotherapy and survival in 262 patients with PC including 158 resectable and 104 unresectable PC. RESULTS: There were more male and younger patients in current smokers than in nonsmokers. In unresectable PC, current smokers had more metastatic tumors than locally advanced tumors compared with nonsmokers. In current smokers receiving chemotherapy, the baseline white blood cell count, neutrophil count, and hemoglobin concentration were significantly higher in current smokers than in nonsmokers. Furthermore, grades 3 to 4 neutropenia was observed more often in nonsmokers than smokers. On the other hand, the performance and efficacy of the planned adjuvant chemotherapy were similar between smokers and nonsmokers. More importantly, there was no significant difference in overall prognosis between smokers and nonsmokers receiving chemotherapy. CONCLUSIONS: Smoking status has no significant impact on the efficacy of current chemotherapy for both resectable and unresectable PC. PMID- 26355553 TI - Percutaneous Catheter Drainage of Pancreatitis-Associated Ascitic Fluid in Early Stage Severe Acute Pancreatitis. PMID- 26355554 TI - Amlodipine for the Medical Treatment of Adult-Onset Diffuse Nesidioblastosis. PMID- 26355555 TI - Pancreatic Hydrocele: A Case Report and Review of Literature. PMID- 26355556 TI - Effects of ractopamine hydrochloride and dietary protein content on performance, carcass traits and meat quality of Nellore bulls. AB - Ractopamine hydrochloride (RH) alters protein metabolism and improves growth performance in Bos taurus cattle with high carcass fat. Our objective was to evaluate the effects of RH, dietary CP and RH*CP interaction on performance, blood metabolites, carcass characteristics and meat quality of young Nellore bulls. A total of 48 bulls were randomly assigned to four treatments in a 2*2 factorial arrangement. The factors were two levels of dietary CP (100% and 120% of metabolizable protein requirement, defined as CP100 and CP120, respectively), and two levels of RH (0 and 300 mg/animal.per day). Treated animal received RH for the final 35 days before slaughter. Animals were weighed at the beginning of the feedlot period (day 63), at the beginning of ractopamine supplementation (day 0), after 18 days of supplementation (day 18) and before slaughter (day 34). Animals were slaughtered and hot carcass weights recorded. After chilling, carcass data was collected and longissimus samples were obtained for determination of meat quality. The 9-11th rib section was removed for carcass composition analysis. Supplementation with RH increased ADG independently of dietary CP. There was a RH*CP interaction on dry matter intake (DMI), where RH reduced DMI at CP120, with no effect at CP100. Ractopamine improved feed efficiency, without RH*CP interaction. Ractopamine had no effect on plasma creatinine and urea concentration. Greater dietary CP tended to increase blood urea, and there was a RH*CP interaction for plasma total protein. Ractopamine supplementation increased plasma total protein at CP120, and had no effect at CP100. Ractopamine also decreased plasma glucose concentration at CP100, but had no effect at CP120. Ractopamine increased alkaline phosphatase activity at CP120 and had no effect at CP100. There was a tendency for RH to increase longissimus muscle area, independently of dietary CP. Ractopamine did not alter fat thickness; however, fat thickness was reduced by greater CP in the diet. Supplementation with RH decreased meat shear force, but only at day 0 of aging, having no effect after 7, 14 or 21 days. Greater dietary protein increased meat shear force after 0 and 7 days of aging, with no effect after 14 or 21 days. These results demonstrate for the first time the efficacy of ractopamine supplementation to improve gain and feed efficiency of intact Bos indicus males, with relatively low carcass fat content. Ractopamine effects were not further improved by increasing dietary protein content above requirements. PMID- 26355557 TI - Pneumonia Associated with an Influenza A H3 Outbreak at a Skilled Nursing Facility--Florida, 2014. AB - In December 2014, the Florida Department of Health, Bureau of Epidemiology, was notified that 18 of 95 (19%) residents at a skilled nursing facility had radiographic evidence of pneumonia and were being treated with antibiotics. Two residents were hospitalized, one of whom died. A second resident died at the facility. The Florida Department of Health conducted an outbreak investigation to ascertain all cases through active case finding, identify the etiology, provide infection control guidance, and recommend treatment or prophylaxis, if indicated. PMID- 26355558 TI - Effects of mechanical horseback riding on the balance ability of the elderly. AB - [Purpose] This study was conducted to evaluate the effect of mechanical horseback riding exercise on the balance ability of the elderly. [Subjects and Methods] Ten elderly patients were assigned to an experimental group, and they performed 15 min of horseback riding. Another 10 elderly patients were assigned to a control group, and they performed 15 min of one-leg standing exercise. Both exercises were repeated five times a week for a total of six weeks. The participants' balance ability was evaluated. [Results] The horseback-riding group showed significant differences between the pre-and post-test balance abilities as assessed by the Berg Balance Scale (BBS) and the Timed Up and Go (TUG) test. [Conclusion] Horseback riding effectively improves the balance ability of the elderly. Horseback riding should be considered as a therapeutic method for the physical therapy of the elderly. PMID- 26355559 TI - Modified Goff Symptom Index: Simple triage tool for ovarian malignancy. AB - OBJECTIVES: Ovarian cancer often goes undiagnosed or misdiagnosed in the early stages. The present study aimed to validate a modified version of the Goff Symptom Index (GSI) in an Indian population. METHODS: This prospective case control study was conducted between July 2010 and June 2012 in a university hospital in Manipal, Karnataka, India. A total of 305 inpatients admitted for ovarian pathology investigations and outpatients undergoing routine gynaecological check-ups were included in the study. The modified GSI (MGSI) was used to investigate the presence, severity, frequency and duration of 10 ovarian cancer symptoms on a scale of 1-5. Four additional symptoms were included with those of the original GSI (two symptoms from a previous MGSI and two new symptoms). Patients were regarded as positive for ovarian cancer if symptoms occurred >12 times per month and time since onset was <1 year. Histopathology confirmed the diagnosis of ovarian tumours. RESULTS: A total of 13 patients were excluded. The final sample (n = 292) was divided into a test group (n = 74) and a control group (n = 218) based on histopathology. Within the controls, 144 women were found to have benign tumours. The MGSI was positive in 71.6% of the test group as opposed to only 11.5% of the control group. The addition of two symptoms (loss of appetite and weight) to the GSI increased the test's sensitivity from 71.6% to 77% without compromising specificity (88.5%). CONCLUSION: Based on these findings, the addition of two new symptoms (loss of appetite and weight) to the GSI is proposed in order to increase the test's sensitivity. However, the addition of urinary symptoms to the GSI requires further validation. PMID- 26355560 TI - Easy access to constrained peptidomimetics and 2,2-disubstituted azetidines by the unexpected reactivity profile of alpha-lithiated N-Boc-azetidines. AB - The reactivity profile of lithiated N-Boc-2-arylazetidines has been investigated filling a gap in the chemistry of this class of four-membered heterocycles. Two unexpected and unprecedented results have been observed: an "ortho-effect" accounting for the regioselective functionalization of the azetidine ring, and self-condensation leading to new and interesting azetidine-based peptidomimetics. PMID- 26355561 TI - Scavenging 4-Oxo-2-nonenal. AB - 4-Oxo-2-nonenal (ONE), a product of cellular lipid oxidation, reacts nonspecifically with the lysine residues of proteins and is generated in increased amounts during degenerative diseases and cancer. We show that pyridoxamine, salicylamine, and related 2-aminomethylphenols react with ONE, to form pyrrolo[2,1-b][1,3]oxazines with the participation of both the amino and the phenolic groups. 2-Aminomethylphenols react with ONE as well as with the Michael adducts of ONE much more rapidly than lysine, suggesting their use for therapeutically scavenging ONE. PMID- 26355562 TI - How could she? Psychosocial analysis of ten homicide cases committed by women. AB - OBJECTIVE: Ten percent of all homicide perpetrators are female and homicidal acts committed by women are mostly a result of interpersonal conflicts. We carried out a retrospective psychosocial analysis of ten homicide cases committed by women with an urban mid-European background. We evaluated characteristic determinants regarding 1) deed circumstances and motives, 2) the perpetrators, and 3) the victims. Results were compared with the literature on female and male homicides. METHOD: Autopsy records of the Institute of Legal Medicine of the University Hospital of Dusseldorf, Germany, during the time period from 2006 to 2011 were searched for homicides committed by female perpetrators. Prosecution files were reviewed for further information. RESULTS: The sample comprised N = 10 female homicide perpetrators and eleven victims. The mentioned determinants of the homicide were fairly consistent. All deeds occurred in the domestic context; they were mostly unplanned. All perpetrators were socially isolated and faced socially challenging situations. Most perpetrators were of low socioeconomic status. Furthermore, all victims were helpless and/or dependent on the perpetrator. The presence of a major psychiatric disorder was uncommon and, in contrast to male perpetrators, most women had no previous convictions. DISCUSSION: The potential value of these core findings in our sample regarding prevention is discussed. PMID- 26355563 TI - Well-Defined Star-Shaped Polyglutamates with Improved Pharmacokinetic Profiles As Excellent Candidates for Biomedical Applications. AB - There is a need to develop new and innovative polymer carriers to be used as drug delivery systems and/or imaging agents owing to the fact that there is no universal polymeric system that can be used in the treatment of all diseases. Additionally, limitations with existing systems, such as a lack of biodegradability and biocompatibility, inevitably lead to side effects and poor patient compliance. New polymer therapeutics based on amino acids are excellent candidates for drug delivery, as they do not suffer from these limitations. This article reports on a simple yet powerful methodology for the synthesis of 3-arm star-shaped polyglutamic acid with well-defined structures, precise molecular weights (MW), and low polydispersity (D = <1.3). These were synthesized by ring opening polymerization (ROP) of N-carboxyanhydrides (NCA) in a divergent method from novel multifunctional initiators. Herein, their exhaustive physicochemical characterization is presented. Furthermore, preliminary in vitro evaluation in selected cell models, and exhaustive in vivo biodistribution and pharmacokinetics, highlighted the advantages of these branched systems when compared with their linear counterparts in terms of cell uptake enhancement and prolonged plasma half-life. PMID- 26355564 TI - Overexpression of CD45RA isoforms in carriers of the C77G mutation leads to hyporeactivity of CD4+CD25highFoxp3+ regulatory T cells. AB - Disorders in regulatory T-cell (T(reg)) function can result in the breakdown of immunological self-tolerance. Thus, the identification of mechanisms controlling the activity of T(reg) is of great relevance. We used T(reg) from individuals carrying the C77G polymorphism as models to study the role of CD45 molecules in humans. C77G prevents splicing of CD45 exon A thereby leading to an aberrant expression pattern of CD45 isoforms in affected individuals. Resting and in vitro expanded/activated CD4(+)CD25(high)Foxp3(+) T(reg) from carriers of C77G strongly expressed CD45RA isoforms whereas these isoforms were almost absent in cells from individuals with wild-type CD45. C77G T(reg) showed diminished upregulation of activation markers, lower phosphorylation of p56(lck)(Y505) and a reduced proliferative potential when stimulated with anti-TcR or anti-TcR plus CD28 mAb suggesting decreased responsiveness to activating stimuli. In addition, the capacity to suppress proliferation of conventional CD4(+) T cells was impaired in C77G T(reg). Furthermore, microarray studies revealed distinct gene expression patterns in T(reg) from C77G carriers. These data suggest that the changes in CD45 isoform combination resulting from the C77G mutation alter the responsiveness of T(reg) to TcR-mediated signaling. Targeting CD45 isoform expression might be a useful approach to modulate T(reg) function. PMID- 26355565 TI - Inflammatory bowel disease (IBD) locus 12: is glutathione peroxidase-1 (GPX1) the relevant gene? AB - Genome-wide association studies have identified and repeatedly confirmed the association of rs3197999 in MST1 with inflammatory bowel disease (IBD). However, the underlying pathophysiology remains unclear. rs3197999 is a non-synonymous single-nucleotide polymorphism which modifies the function of macrophage stimulating protein-1 (MST1). We show by haplotyping that rs3197999 is in linkage disequilibrium with rs1050450 in GPX1, with almost complete cosegregation of the minor alleles. As shown by immunoassay, rs3197999 influences the MST-1 level in serum. But also rs1050450 causes an amino acid exchange in glutathione peroxidase 1 (GPx-1) and reduced activity of this antioxidant enzyme. The association of GPx deficiency and IBD in mice was already shown. We propose that GPx-1 is a better candidate than MST1 for the pathophysiologic link between IBD locus 12 and IBD. PMID- 26355566 TI - Identification of a novel ovine LH-beta promoter region, which dramatically enhances its promoter activity. AB - The luteinizing hormone beta subunit (LH-beta) gene plays a critical role in reproduction. In order to characterize and analyze the promoter region of LH-beta in sheep, a genomic library was constructed in phage lambda gt 10 and screened. A novel region of 1,224 bp upstream from the targeted LH-beta gene was identified. Blasting this sequence showed a perfect homology for the first 721 bp sequence with an upstream ovine LH-beta sequence in the database. However, the remaining 5'-503 bp showed no sequence matching. DNA from Moroccan breeds was isolated and the whole region was amplified and confirmed by sequencing. To further confirm the promoter activity of this region, an in vitro analysis using a luciferase assay was carried out. An increase in the promoter activity of the whole region was demonstrated compared to the empty vector. More interestingly, the unpublished region significantly enhanced the promoter activity compared to the known region alone. To predict putative transcription factor binding-sites (TFBSs), an in silico analysis was performed using the TFSEARCH program. The region features many TFBSs and contains two palindrome sequences of 17- and 18 bp. Taken together, a novel region was identified and confirmed in sheep which contained a promoter activity rich with binding sites for a putative regulatory element as shown in silico. PMID- 26355567 TI - Turnover of the actomyosin complex in zebrafish embryos directs geometric remodelling and the recruitment of lipid droplets. AB - Lipid droplets (LDs), reservoirs of cholesterols and fats, are organelles that hydrolyse lipids in the cell. In zebrafish embryos, the actomyosin complex and filamentous microtubules control the periodic regulation of the LD geometry. Contrary to the existing hypothesis that LD transport involves the kinesin microtubule system, we find that their recruitment to the blastodisc depends on the actomyosin turnover and is independent of the microtubules. For the first time we report the existence of two distinct states of LDs, an inactive and an active state, that occur periodically, coupled weakly to the cleavage cycles. LDs are bigger, more circular and more stable in the inactive state in which the geometry of the LDs is maintained by actomyosin as well as microtubules. The active state has smaller and irregularly shaped LDs that show shape fluctuations that are linked to actin depolymerization. Because most functions of LDs employ surface interactions, our findings on the LD geometry and its regulation bring new insights to the mechanisms associated with specific functions of LDs, such as their storage capacity for fats or proteins, lipolysis etc. PMID- 26355568 TI - Interference-free Micro/nanoparticle Cell Engineering by Use of High-Throughput Microfluidic Separation. AB - Engineering cells with active-ingredient-loaded micro/nanoparticles is becoming increasingly popular for imaging and therapeutic applications. A critical yet inadequately addressed issue during its implementation concerns the significant number of particles that remain unbound following the engineering process, which inadvertently generate signals and impart transformative effects onto neighboring nontarget cells. Here we demonstrate that those unbound micro/nanoparticles remaining in solution can be efficiently separated from the particle-labeled cells by implementing a fast, continuous, and high-throughput Dean flow fractionation (DFF) microfluidic device. As proof-of-concept, we applied the DFF microfluidic device for buffer exchange to sort labeled suspension cells (THP-1) from unbound fluorescent dye and dye-loaded micro/nanoparticles. Compared to conventional centrifugation, the depletion efficiency of free dyes or particles was improved 20-fold and the mislabeling of nontarget bystander cells by free particles was minimized. The microfluidic device was adapted to further accommodate heterogeneous-sized mesenchymal stem cells (MSCs). Complete removal of unbound nanoparticles using DFF led to the usage of engineered MSCs without exerting off-target transformative effects on the functional properties of neighboring endothelial cells. Apart from its effectiveness in removing free particles, this strategy is also efficient and scalable. It could continuously process cell solutions with concentrations up to 10(7) cells.mL(-1) (cell densities commonly encountered during cell therapy) without observable loss of performance. Successful implementation of this technology is expected to pave the way for interference-free clinical application of micro/nanoparticle engineered cells. PMID- 26355569 TI - Reversal of T-cell exhaustion as a strategy to improve immune control of HIV-1. PMID- 26355570 TI - A phylotype-based analysis highlights the role of drug-naive HIV-positive individuals in the transmission of antiretroviral resistance in the UK. AB - OBJECTIVE: Antiretroviral-naive HIV-positive individuals contribute to the transmission of drug-resistant viruses, compromising first-line therapy. Using phylogenetic inference, we quantified the proportion of transmitted drug resistance originating from a treatment-naive source. METHODS: Using a novel phylotype-based approach, 24 550 HIV-1 subtype B partial pol gene sequences from the UK HIV Drug Resistance database were analysed. Ongoing transmission of drug resistance amongst HIV-positive individuals was identified as phylotypes of at least three sequences with at least one shared drug resistance mutation, a maximum intra-clade genetic distance of 4.0% and a basal branch support at least 90%. The time of persistence of the transmission chains was estimated using a fast least-squares molecular clock inference approach. RESULTS: Around 70% of transmitted drug-resistance had a treatment-naive source. The most commonly transmitted mutations were L90M in the protease gene and K103N, T215D and T215S in reverse transcriptase. Reversion to wild type occurred at a low frequency and drug-independent reservoirs of resistance have persisted for up to 13 years. CONCLUSION: These results illustrate the impact of viral fitness on the establishment of resistance reservoirs and support the notion that earlier diagnoses and treatment of HIV infections are warranted for counteracting the spread of antiretroviral resistance. Phylotype-based phylogenetic inference is an attractive approach for the routine surveillance of transmitted drug resistance in HIV as well as in other pathogens for which genotypic resistance data are available. PMID- 26355571 TI - Stromal immune infiltration in HIV-related diffuse large B-cell lymphoma is associated with HIV disease history and patient survival. AB - OBJECTIVE: Understanding tumor microenvironment and its impact on prognosis of HIV-related lymphomas may provide insight into novel therapeutic strategies. DESIGN: We characterized the relationship between infiltrating immune cells with tumor characteristics, HIV disease history and survival in 80 patients with HIV related diffuse large B-cell lymphoma (DLBCL) diagnosed in the era of combined antiretroviral therapy (1996-2007) at Kaiser Permanente California. Eighty patients with HIV-unrelated DLBCL were included for comparison. METHODS: Data on patients' clinical history were obtained from Kaiser Permanente's electronic health records. The density of stromal CD4, CD8 and FOXP3 T cells and CD68 macrophages, as well as tumor molecular characteristics were examined using immunohistochemistry. The associations between stromal immune infiltration and patient's clinical history or tumor characteristics were examined using Kruskal Wallis tests or Pearson's correlation coefficient. The effect of stromal immune infiltration on 2-year mortality was evaluated in multivariable logistic regression. RESULTS: Compared with HIV-unrelated DLBCL, patients with HIV-related DLBCL had significantly reduced stromal CD4 and FOXP3 T cells, but increased density of macrophages. Increased density of stromal macrophages was correlated with lower circulating CD4 cell count at DLBCL diagnosis. Tumor molecular characteristics, including BCL6, p53 and cMYC expression, but not Epstein-Barr virus infection status, were significantly correlated with stromal immune infiltration, particularly FOXP3 T cells. A higher density of infiltrating CD8 T cell was significantly associated with reduced mortality in patients with HIV related DLBCL (odds ratio = 0.30 [0.09-0.97] for >=25 vs. <10%). CONCLUSION: These data provide evidence for the prognostic significance of cytotoxic T cells in determining outcomes of HIV-related lymphoma. PMID- 26355572 TI - A low HIV-DNA level in peripheral blood mononuclear cells at antiretroviral treatment interruption predicts a higher probability of maintaining viral control. AB - OBJECTIVE: The main aim of this study was to determine whether HIV replication can be controlled following interruption of treatment started early in the course of infection (CD4 >350 cells/MUl and viral load <50 000 copies/ml), but not during the primary infection. METHODS: Patients enrolled in a multicenter trial of treatment interruption (ANRS 116 SALTO) with CD4 above 450 cells/MUl and viral load below 400 copies/ml at treatment interruption were selected for this second analysis. We determined the proportion of patients whose plasma HIV-RNA load remained below 400 copies/ml during the first 12 months of treatment interruption, and baseline factors predictive of time to loss of viral control. Viral load rebound was defined as two successive values above 400 copies/ml, or as one value above 400 copies/ml, followed by treatment resumption. RESULTS: We studied 95 patients with a median CD4 nadir of 382 cells/MUl (340-492). At treatment interruption, the median CD4 cell count and HIV-DNA load were 813/MUl (695-988) and 206 copies/10 peripheral blood mononuclear cells (PBMCs) (53-556). Twelve months after treatment interruption, seven patients still had viral load below 400 copies/ml (Kaplan-Meier estimate 7.5%, 95% confidence interval 3.7 14.6), and four of them still had viral load below 400 copies/ml at 36 months. A multivariable Cox proportional-hazards model showed that time to loss of viral control was more shorter in patients with HIV-DNA at least 150 copies/10 PBMCs at treatment interruption (hazard ratio 2.1, 95% confidence interval 1.3-3.3, P = 0.002) than in those with HIV-DNA below 150 copies/10 PBMCs. CONCLUSION: Patients who have low HIV-DNA levels at antiretroviral treatment interruption are more likely to maintain viral control for long periods. PMID- 26355573 TI - Growth reconstitution following antiretroviral therapy and nutritional supplementation: systematic review and meta-analysis. AB - OBJECTIVE: As antiretroviral therapy (ART) expands for HIV-infected children, it is important to determine its impact on growth. We quantified growth and its determinants following ART in resource-limited (RLS) and developed settings. DESIGN: Systematic review and meta-analysis. METHODS: We searched publications reporting growth [weight-for-age (WAZ), height-for-age (HAZ), and weight-for height (WHZ) z scores] in HIV-infected children following ART through August 2014. Inclusion criteria were as follows: younger than 18 years; ART; at least 20 patients; growth at ART; and post-ART growth. Standardized and overall weighted mean differences were calculated using random-effects models. RESULTS: A total of 67 articles were eligible (RLS = 54; developed settings = 13). Mean age was 5.8 years, and comparable between settings (P = 0.90). Baseline growth was substantially lower in RLS vs. developed settings (WAZ -2.1 vs. -0.5; HAZ -2.2 vs. -0.9; both P < 0.01). Rate of weight but not height reconstitution during 12 and 24 months was higher in RLS (12-month WAZ change 0.84 vs. 0.17, P < 0.01). Growth deficits persisted in RLS after 2 years ART (P = 0.04). Younger cohort age was associated with greater growth reconstitution. Protease inhibitor and nonnucleoside reverse-transcriptase inhibitor regimens yielded comparable growth. Adjusting for age and setting, cohorts with nutritional supplements had greater growth gains (24-month rate difference: WAZ 0.55, P = 0.03; HAZ 0.60, P = 0.007). Supplement benefits were attenuated after adjusting for baseline cohort growth. CONCLUSION: RLS children had substantial growth deficits compared with developed settings counterparts at ART; growth shortfalls in RLS persisted despite reconstitution. Earlier age and nutritional supplementation at ART may improve growth outcomes. Scant data on supplementation limit evaluation of impact and underscores need for systematic data collection regarding supplementation in pediatric ART programmes/cohorts. PMID- 26355574 TI - Modelling the impact and cost-effectiveness of combination prevention amongst HIV serodiscordant couples in Nigeria. AB - OBJECTIVE: To estimate the impact and cost-effectiveness of treatment as prevention (TasP), pre-exposure prophylaxis (PrEP) and condom promotion for serodiscordant couples in Nigeria. DESIGN: Mathematical and cost modelling. METHODS: A deterministic model of HIV-1 transmission within a cohort of serodiscordant couples and to/from external partners was parameterized using data from Nigeria and other African settings. The impact and cost-effectiveness were estimated for condom promotion, PrEP and/or TasP, compared with a baseline where antiretroviral therapy (ART) was offered according to 2010 national guidelines (CD4 <350 cells/MUl) to all HIV-positive partners. The impact was additionally compared with a baseline of current ART coverage (35% of those with CD4 <350 cells/MUl). Full costs (in US $2012) of programme introduction and implementation were estimated from a provider perspective. RESULTS: Substantial benefits came from scaling up ART to all HIV-positive partners according to 2010 national guidelines, with additional smaller benefits of providing TasP, PrEP or condom promotion. Compared with a baseline of offering ART to all HIV-positive partners at the 2010 national guidelines, condom promotion was the most cost-effective strategy [US $1206/disability-adjusted-life-year (DALY)], the next most cost effective intervention was to additionally give TasP to HIV-positive partners (incremental cost-effectiveness ratio US $1607/DALY), followed by additionally giving PrEP to HIV-negative partners until their HIV-positive partners initiate ART (US $7870/DALY). When impact was measured in terms of infections averted, PrEP with condom promotion prevented double the number of infections as condom promotion alone. CONCLUSIONS: The first priority intervention for serodiscordant couples in Nigeria should be scaled up ART access for HIV-positive partners. Subsequent incremental benefits are greatest with condom promotion and TasP, followed by PrEP. PMID- 26355575 TI - Assessing transmissibility of HIV-1 drug resistance mutations from treated and from drug-naive individuals. AB - OBJECTIVES: Surveillance drug resistance mutations (SDRMs) in drug-naive patients are typically used to survey HIV-1-transmitted drug resistance (TDR). We test here how SDRMs in patients failing treatment, the original source of TDR, contribute to assessing TDR, transmissibility and transmission source of SDRMs. DESIGN: This is a retrospective observational study analyzing a Portuguese cohort of HIV-1-infected patients. METHODS: The prevalence of SDRMs to protease inhibitors, nucleoside reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) in drug-naive and treatment-failing patients was measured for 3554 HIV-1 subtype B patients. Transmission ratio (prevalence in drug-naive/prevalence in treatment-failing patients), average viral load and robust linear regression with outlier detection (prevalence in drug-naive versus in treatment-failing patients) were analyzed and used to interpret transmissibility. RESULTS: Prevalence of SDRMs in drug-naive and treatment-failing patients were linearly correlated, but some SDRMs were classified as outliers - above (PRO: D30N, N88D/S, L90 M, RT: G190A/S/E) or below (RT: M184I/V) expectations. The normalized regression slope was 0.073 for protease inhibitors, 0.084 for NRTIs and 0.116 for NNRTIs. Differences between SDRMs transmission ratios were not associated with differences in viral loads. CONCLUSION: The significant linear correlation between prevalence of SDRMs in drug-naive and in treatment-failing patients indicates that the prevalence in treatment-failing patients can be useful to predict levels of TDR. The slope is a cohort-dependent estimate of rate of TDR per drug class and outlier detection reveals comparative persistence of SDRMs. Outlier SDRMs with higher transmissibility are more persistent and more likely to have been acquired from drug-naive patients. Those with lower transmissibility have faster reversion dynamics after transmission and are associated with acquisition from treatment failing patients. PMID- 26355576 TI - Choice of effect measure in HIV randomized trials. AB - Comparing the results of HIV trials using different endpoints and scale is a difficult task. The two main primary endpoints are the proportion of patients with HIV-1 RNA less than 50 copies/ml at week 48 and the time to virologic failure. In the A5202 study, the use of the risk difference scale instead of the risk ratio scale would have led to equivalence in the comparisons between efavirenz and atazanavir/ritonavir. We discuss these results and their impact on the design of the A5257, as well as alternative approaches. PMID- 26355577 TI - Effects of consecutive application of stretching, Schroth, and strengthening exercises on Cobb's angle and the rib hump in an adult with idiopathic scoliosis. AB - [Purpose] To report the effects of consecutive application of stretching, Schroth, and strengthening exercises in an adult with idiopathic scoliosis. [Subject] A 26-year-old woman with idiopathic scoliosis, Cobb's angle of 20.51 degrees , and back pain. [Methods] The exercise program consisted of 3 sessions: 10 minutes of stretching exercises, 20 minutes of Schroth exercises, and 10 minutes of strengthening exercises. This program was implemented 3 times a week, for 8 weeks. [Results] The thoracic Cobb's angle decreased from 20.51 degrees to 16.35 degrees , and the rib hump decreased from 15 degrees to 9 degrees . [Conclusion] Consecutive application of stretching, Schroth, and strengthening exercises may help reduce Cobb's angle and the rib hump in adults with idiopathic scoliosis. PMID- 26355579 TI - Agreement Between Doppler and Invasive Blood Pressure Monitoring in Anesthetized Dogs Weighing <5 kg. AB - The objectives of this study were to determine if Doppler (DOP) blood pressure measurements more closely estimate either invasive systolic or invasive mean arterial blood pressures (ISAP or IMAP, respectively) in small dogs under general anesthesia and to assess the ability of DOP to detect anesthesia-related hypotension in small dogs. Blood pressure measurements (n = 203) were obtained from 10 client-owned dogs. DOP, ISAP, and IMAP were recorded simultaneously, and the data were categorized into two groups: hypotensive (ISAP <90 mm Hg) and normotensive (ISAP >=90 mm Hg and <=160 mm Hg). DOP overestimated ISAP and IMAP in both the normotensive and hypotensive groups. The DOP was highly specific (97%) but poorly sensitive (56%) for detecting hypotension. The smallest bias was achieved when using DOP as an estimate of systolic arterial blood pressure in both normotensive and hypotensive dogs, suggesting that DOP measures systolic arterial blood pressure in dogs <5 kg. For dogs with hypotension, DOP met all of the performance criteria for noninvasive blood pressure monitors recommended by the American College of Veterinary Internal Medicine. DOP is an acceptably accurate and highly specific means of detecting hypotension in small dogs under general anesthesia. PMID- 26355578 TI - Hypercalcemia: Pathophysiology, Clinical Signs, and Emergent Treatment. AB - Hypercalcemia is uncommonly encountered in veterinary patients. When it does occur, the effects can be severe, resulting in significant morbidity and mortality if not recognized and addressed in a timely manner. Causes of hypercalcemia are varied and include pituitary-dependent and pituitary independent causes. A diagnosis of hypercalcemia should be made based on documentation of ionized hypercalcemia. The mainstay of emergency treatment usually involves aggressive IV fluid diuresis, the use of diuretics, and, often, glucocorticoids. The use of bisphosphonates has become increasingly more common in veterinary medicine. PMID- 26355580 TI - Sensitivity and Specificity of Histoplasma Antigen Detection by Enzyme Immunoassay. AB - The objective of this study was to evaluate the sensitivity and specificity of an antigen enzyme immunoassay (EIA) on urine samples for the diagnosis of histoplasmosis in dogs. This retrospective medical records review included canine cases with urine samples submitted for Histoplasma EIA antigen assay between 2007 and 2011 from three veterinary institutions. Cases for which urine samples were submitted for Histoplasma antigen testing were reviewed and compared to the gold standard of finding Histoplasma organisms or an alternative diagnosis on cytology or histopathology. Sensitivity, specificity, negative predictive value, positive predictive value, and the kappa coefficient and associated confidence interval were calculated for the EIA-based Histoplasma antigen assay. Sixty cases met the inclusion criteria. Seventeen cases were considered true positives based on identification of the organism, and 41 cases were considered true negatives with an alternative definitive diagnosis. Two cases were considered false negatives, and there were no false positives. Sensitivity was 89.47% and the negative predictive value was 95.35%. Specificity and the positive predictive value were both 100%. The kappa coefficient was 0.9207 (95% confidence interval, 0.8131-1). The Histoplasma antigen EIA test demonstrated high specificity and sensitivity for the diagnosis of histoplasmosis in dogs. PMID- 26355581 TI - Mucinous Pleural Effusion in a Dog with a Pulmonary Adenocarcinoma and Carcinomatosis. AB - An 11 yr old castrated male greyhound presented to the Washington State University's Veterinary Teaching Hospital (WSU VTH) for evaluation of a 4 day history of pleural effusion. The pleural effusion had a gelatinous appearance, suggestive of mucus, and was characterized cytologically as a pyogranulomatous exudate with some features suggestive of a carcinoma. Postmortem examination identified a pulmonary mass with evidence of carcinomatosis. Pulmonary papillary adenocarcinoma with carcinomatosis was the histologic diagnosis. Abundant mucin production was present, consistent with a mucinous pulmonary adenocarcinoma. To the authors' knowledge, this is the first report of a mucinous pulmonary adenocarcinoma with mucus pleural effusion in a dog. PMID- 26355582 TI - Extraskeletal Osteosarcoma Induced by a Foreign Body Granuloma. AB - An 8 yr old spayed female Italian greyhound was presented with a mass in the cranial abdomen. Preliminary evaluation of the dog revealed a large, cavitary, irregularly shaped mass with no definitive association with any abdominal organs. During an exploratory celiotomy, a 16 cm * 12 cm * 6 cm mass was removed. On subsequent histopathology, extraskeletal osteosarcoma induced by a foreign body granuloma was diagnosed. The foreign body granuloma, based on histopathological findings, was suspected to be secondary to a retained surgical sponge from her routine ovariohysterectomy performed 7 yr prior to presentation. Animals with granulomas induced by foreign bodies can remain asymptomatic for years; however, those granulomas can progress to extraskeletal osteosarcomas, which carry a poor prognosis. PMID- 26355583 TI - Angiostrongylus vasorum Causing Severe Granulomatous Hepatitis with Concurrent Multiple Acquired PSS. AB - A 14 mo old female Jack Russell terrier presented with a 12 hr history of vomiting and inappetence. She was subsequently diagnosed with multiple acquired portosystemic shunts during an exploratory celiotomy. Gross and histopathological hepatic abnormalities were consistent with chronic disease, including features suggestive of portal hypertension that was potentially caused by migrating and resident Angiostrongylus vasorum larvae. Fecal analysis and polymerase chain reaction of hepatic tissue confirmed the presence of Angiostrongylus vasorum . The dog recovered clinically following empirical treatment and supportive care. A lack of parasite burden was confirmed 9 wk postdiagnosis; however, serum biochemical analysis at that time was suggestive of ongoing hepatic dysfunction. PMID- 26355584 TI - Removal of an Airway Foreign Body via Flexible Endoscopy Through a Laryngeal Mask Airway. AB - A Silky terrier weighing 4.7 kg was presented with an airway foreign body after having aspirated a fragment of an orotracheal tube that was identified on radiological examination. Due to the small size of the patient, flexible endoscopy could not be performed through the lumen of a tracheal tube. Following IV induction of general anesthesia, the airway was instrumented with a laryngeal mask airway that was attached via a three-way connector to an anesthesia breathing circuit. A flexible endoscope was passed through the free port of the connector. That arrangement allowed for the passage of an endoscope through the lumen of the laryngeal mask airway and into the trachea without interrupting the continuous supply of O2 and sevoflurane. PMID- 26355585 TI - Severe Pit Viper Envenomation with Extended Clinical Signs and Treatment Complications in a Dog. AB - This manuscript describes the extended clinical abnormalities that can occur in severe snake envenomation and the clinical signs associated with antivenom hypersensitivity in a 3 yr old dog. Treatment consisted of IV fluid therapy, analgesics, a vasopressor, cardiac antiarrhythmia drugs, and polyvalent pit viper antivenom. Following initial response to treatment, relapse of clinical signs occurred. Most interesting was the recrudescence of clinical signs on day 7 that may have been caused by the release of deposited venom during surgical debridement of necrotic skin. The resulting extensive clinical signs required multiple vials of antivenom (22 vials over a 7 day period). Both F(ab')2 antivenom and antivenin (Crotalidae) polyvalent were used in this dog because of availability logistics. It is thought that this large amount of antivenom resulted in type I (anaphylaxis) and type III hypersensitivity (serum sickness) reactions. The dog made a complete clinical recovery. This description of extended, fluctuating clinical abnormalities that were associated with envenomation together with the development of hypersensitivity reactions that were presumably secondary to antivenom administration is information that can be useful for the management of patients afflicted with severe pit viper envenomation. PMID- 26355586 TI - Urinary Aldosterone/Creatinine Ratio After Fludrocortisone Suppression Consistent with PHA in a Cat. AB - A 9 yr old cat was presented with clinical signs and laboratory abnormalities attributed to arterial hypertension (mean systolic arterial pressure, 290 mm Hg). Plasma aldosterone concentration was increased at the time of admission (651 pmol/L), but serum creatinine and potassium concentrations were within the reference range. A second increased aldosterone (879 pmol/L) and normal plasma renin activity (1.85 ng/mL/hr) resulted in an increased aldosterone/renin ratio, which was suggestive of primary hyperaldosteronism (PHA). To further support the diagnosis of PHA, the urinary aldosterone/creatinine ratio was calculated both before and after oral administration of fludrocortisone acetate (0.05 mg/kg q 12 hr for 4 consecutive days). The urinary aldosterone/creatinine ratio was 92.6 * 10(-9) before fludrocortisone administration and 155.8 * 10(-9) 4 days later. Absence of suppression was typical of PHA. The cat had a limited response to antihypertensive medication and died before treatment for PHA could be instituted. A necropsy was not permitted by the owner. PMID- 26355587 TI - Ectopic Intrathoracic Hepatic Tissue and Accessory Lung Lobe Aplasia in a Dog. AB - A 6 yr old male Yorkshire terrier was presented for an ~6 yr history of progressive cough and dyspnea. Thoracic radiographs revealed a 6 cm diameter mass within the right caudal thorax. Thoracic ultrasound identified an intrathoracic mass ultrasonographically consistent with liver tissue and a chronic diaphragmatic hernia was suspected. Exploratory laparotomy was performed, but no evidence of a diaphragmatic hernia was identified. Thoracic exploration identified abnormal lung parenchyma. The accessory lung lobe was removed using a stapling devise near its base. The consolidated mass had the gross appearance of liver and was histologically identified as ectopic hepatic tissue. Ectopic hepatic tissue, unlike ectopic splenic and pancreatic tissue, is rare and generally has a subdiaphragmatic distribution. This solitary case report demonstrates that ectopic intrathoracic hepatic tissue should be considered a differential diagnosis for a caudal mediastinal mass. PMID- 26355588 TI - Regional Nodal Metastasis of Humeral Chondrosarcoma in a Dog. AB - A 6 yr old castrated male English springer spaniel was evaluated with a 1 mo history of progressive right forelimb lameness with recent swelling around the elbow joint. Physical examination findings included lameness of the right forelimb, muscle atrophy around the right shoulder, grade 2/6 heart murmur, and moderate dental disease. Results of a complete blood cell count and serum biochemical analysis were unremarkable with the exception of a mildly increased alkaline phosphatase (368 U/L; reference range, 128-328 U/L). Radiographs of the right elbow revealed a mixed lytic and proliferative osseous lesion most consistent with either neoplasia or infection. Thoracic radiographs and the echocardiogram were unremarkable. Fine-needle aspiration of the bone lesion was performed. The cytological diagnosis was chondrosarcoma. The right forelimb was amputated and the axillary lymph nodes were collected. Histopathological examination of the bone lesion and axillary lymph nodes revealed chondrosarcoma with metastasis to the lymph nodes. Lymph node metastasis of chondrosarcoma is rare and needs to be further evaluated as a prognostic indicator. PMID- 26355589 TI - Pierre Robin Sequence: A Familial, Clinical, and Pathoanatomical Record of an Affected Dachshund. AB - This study describes a spontaneous case of Pierre Robin sequence in a nonhuman animal species. A miniature dachshund with micrognathia developed glossoptosis, respiratory distress, dysphagia, temporomandibular ankylosis, and a misaligned upper jaw. The severity of this condition resulted in death by obstructive apnea at the age of 8 mo. Dogs with Pierre Robin sequence can provide further knowledge and a greater understanding of this abnormality, leading to better management of affected individuals and improvement of therapeutic methods. PMID- 26355590 TI - Miscibility Gap Closure, Interface Morphology, and Phase Microstructure of 3D Li(x)FePO4 Nanoparticles from Surface Wetting and Coherency Strain. AB - We study the mesoscopic effects which modify phase-segregation in LixFePO4 nanoparticles using a multiphysics phase-field model implement on a high performance cluster. We simulate 3D spherical particles of radii from 3 to 40 nm and examine the equilibrium microstructure and voltage profiles as they depend on size and overall lithiation. The model includes anisotropic, concentration dependent elastic moduli, misfit strain, and facet dependent surface wetting within a Cahn-Hilliard formulation. We find that the miscibility gap vanishes for particles of radius ~5 nm, and the solubility limits change with overall particle lithiation. Surface wetting stabilizes minority phases by aligning them with energetically beneficial facets. The equilibrium voltage profile is modified by these effects in magnitude, and the length and slope of the voltage plateau during two-phase coexistence. PMID- 26355591 TI - All-Aqueous Directed Assembly Strategy for Forming High-Capacity, Stable Silicon/Carbon Anodes for Lithium-Ion Batteries. AB - Silicon (Si) particles have emerged as a promising active material for next generation lithium-ion battery anodes. However, the large volume changes during lithiation/delithiation cycles result in fracture and pulverization of Si, leading to rapid fading of performance. Here, we report a simple, all-aqueous, directed assembly-based strategy to fabricate Si-based anodes that show capacity and capacity retention that are comparable or better than other more complex methods for forming anodes. We use a cationic surfactant, cetyltrimethylammonium bromide (CTAB), to stabilize Si nanoparticles (SiNPs) in water. This suspension is added to an aqueous suspension of para-amino benzoic acid-terminated carbon black (CB), pH 7. Charge interactions cause the well-dispersed SiNP to bind to the CB, allowing most of the SiNP to be available for lithiation and charge transfer. The CB forms a conducting network when the suspension pH is lowered. The dried SiNP/CTAB/CB anode exhibits a capacity of 1580 mAh g(-1) and efficiency of 97.3% after 50 cycles at a rate of 0.1C, and stable performance at cycling rates up to 5C. The directed spatial organization of the SiNP and CB using straightforward colloidal principles allows good contact between the well dispersed active material and the electrically conducting network. The pore space in the CB network accommodates volume changes in the SiNPs. When CTAB is not used, the SiNPs form aggregates in the suspension, and do not contact the CB effectively. Therefore, the electrochemical performance of the SiNP/CB anode is inferior to that of the SiNP/CTAB/CB anode. This aqueous-based, room temperature, directed assembly technique is a new, but simple, low-cost scalable method to fabricate stable Si-based anodes for lithium-ion batteries with performance characteristics that match those made by other more sophisticated techniques. PMID- 26355593 TI - Comparative analysis of gene regulatory networks: from network reconstruction to evolution. AB - Regulation of gene expression is central to many biological processes. Although reconstruction of regulatory circuits from genomic data alone is therefore desirable, this remains a major computational challenge. Comparative approaches that examine the conservation and divergence of circuits and their components across strains and species can help reconstruct circuits as well as provide insights into the evolution of gene regulatory processes and their adaptive contribution. In recent years, advances in genomic and computational tools have led to a wealth of methods for such analysis at the sequence, expression, pathway, module, and entire network level. Here, we review computational methods developed to study transcriptional regulatory networks using comparative genomics, from sequence to functional data. We highlight how these methods use evolutionary conservation and divergence to reliably detect regulatory components as well as estimate the extent and rate of divergence. Finally, we discuss the promise and open challenges in linking regulatory divergence to phenotypic divergence and adaptation. PMID- 26355592 TI - Genetics of gonadal stem cell renewal. AB - Stem cells are necessary for the maintenance of many adult tissues. Signals within the stem cell microenvironment, or niche, regulate the self-renewal and differentiation capability of these cells. Misregulation of these signals through mutation or damage can lead to overgrowth or depletion of different stem cell pools. In this review, we focus on the Drosophila testis and ovary, both of which contain well-defined niches, as well as the mouse testis, which has become a more approachable stem cell system with recent technical advances. We discuss the signals that regulate gonadal stem cells in their niches, how these signals mediate self-renewal and differentiation under homeostatic conditions, and how stress, whether from mutations or damage, can cause changes in cell fate and drive stem cell competition. PMID- 26355594 TI - Using Imiquimod-Induced Psoriasis-Like Skin as a Model to Measure the Skin Penetration of Anti-Psoriatic Drugs. AB - OBJECTIVE: Psoriasis is a chronic inflammatory skin disease and topical therapy remains a key role for treatment. The aim of this study is to evaluate the influence of psoriasis-like lesions on the cutaneous permeation of anti-psoriatic drugs. METHODS: We first set up imiquimod-induced dermatitis in mice that closely resembles human psoriasis lesions. The development of the lesions is based on the IL-23/IL17A axis for phenotypical and histological characteristics. Four drugs, 5 aminolevulinic acid (ALA), tacrolimus, calcipotriol, and retinoic acid, were used to evaluate percutaneous absorption. RESULTS: The most hydrophilic molecule, ALA, revealed the greatest enhancement on skin absorption after imiquimod treatment. Imiquimod increased the skin deposition and flux of ALA by 5.6 to 14.4-fold, respectively, compared to normal skin. The follicular accumulation of ALA was also increased 3.8-fold. The extremely lipophilic drug retinoic acid showed a 1.7 and 3.8-fold increase in skin deposition and flux, respectively. Tacrolimus flux was enhanced from 2 to 21 MUg/cm2/h by imiquimod intervention. However, imiquimod did not promote skin deposition of this macrolide. The lipophilicity, but not the molecular size, dominated drug permeation enhancement by psoriatic lesions. The in vivo percutaneous absorption of ALA and rhodamine B examined by confocal microscopy confirmed the deficient resistance of epidermal barrier for facilitating cutaneous delivery of drugs via psoriasis-like skin. CONCLUSION: We established the topical delivery profiles of anti-psoriatic drugs via imiquimod treated psoriasis-like skin. PMID- 26355595 TI - Assessment of Genetic Diversity and Population Genetic Structure of Corylus mandshurica in China Using SSR Markers. AB - Corylus mandshurica, also known as pilose hazelnut, is an economically and ecologically important species in China. In this study, ten polymorphic simple sequence repeat (SSR) markers were applied to evaluate the genetic diversity and population structure of 348 C. mandshurica individuals among 12 populations in China. The SSR markers expressed a relatively high level of genetic diversity (Na = 15.3, Ne = 5.6604, I = 1.8853, Ho = 0.6668, and He = 0.7777). According to the coefficient of genetic differentiation (Fst = 0.1215), genetic variation within the populations (87.85%) were remarkably higher than among populations (12.15%). The average gene flow (Nm = 1.8080) significantly impacts the genetic structure of C. mandshurica populations. The relatively high gene flow (Nm = 1.8080) among wild C. mandshurica may be caused by wind-pollinated flowers, highly nutritious seeds and self-incompatible mating system. The UPGMA (unweighted pair group method of arithmetic averages) dendrogram was divided into two main clusters. Moreover, the results of STRUCTURE analysis suggested that C. mandshurica populations fell into two main clusters. Comparison of the UPGMA dendrogram and the Bayesian STRUCTURE analysis showed general agreement between the population subdivisions and the genetic relationships among populations of C. mandshurica. Group I accessions were located in Northeast China, while Group II accessions were in North China. It is worth noting that a number of genetically similar populations were located in the same geographic region. The results further showed that there was obvious genetic differentiation among populations from Northeast China to North China. Results from the Mantel test showed a weak but still significant positive correlation between Nei's genetic distance and geographic distance (km) among populations (r = 0.419, P = 0.005), suggesting that genetic differentiation in the 12 C. mandshurica populations might be related to geographic distance. These data provide comprehensive information for the development of conservation strategies of these valuable hazelnut resources. PMID- 26355596 TI - Arsenite Targets the Zinc Finger Domains of Tet Proteins and Inhibits Tet Mediated Oxidation of 5-Methylcytosine. AB - Arsenic toxicity is a serious public health problem worldwide that brings more than 100 million people into the risk of arsenic exposure from groundwater and food contamination. Although there is accumulating evidence linking arsenic exposure with aberrant cytosine methylation in the global genome or at specific genomic loci, very few have investigated the impact of arsenic on the oxidation of 5-methylcytosine (5-mC) mediated by the Ten-eleven translocation (Tet) family of proteins. Owing to the high binding affinity of As(III) toward cysteine residues, we reasoned that the highly conserved C3H-type zinc fingers situated in Tet proteins may constitute potential targets for arsenic binding. Herein, we found that arsenite could bind directly to the zinc fingers of Tet proteins in vitro and in cells, and this interaction substantially impaired the catalytic efficiency of Tet proteins in oxidizing 5-mC to 5-hydroxymethylcytosine (5-hmC), 5-formylcytosine (5-foC), and 5-carboxylcytosine (5-caC). Treatments with arsenite also led to a dose-dependent decrease in the level of 5-hmC, but not 5 mC, in DNA isolated from HEK293T cells overexpressing the catalytic domain of any of the three Tet proteins and from mouse embryonic stem cells. Together, our study unveiled, for the first time, that arsenite could alter epigenetic signaling by targeting the zinc fingers of Tet proteins and perturbing the Tet mediated oxidation of 5-mC in vitro and in cells. Our results offer important mechanistic understanding of arsenic epigenotoxicity and carcinogenesis in mammalian systems and may lead to novel approaches for the chemoprevention of arsenic toxicity. PMID- 26355597 TI - Mutagenesis by AID: Being in the Right Place at the Right Time. PMID- 26355598 TI - Local Anesthetic Peripheral Nerve Block Adjuvants for Prolongation of Analgesia: A Systematic Qualitative Review. AB - BACKGROUND: The use of peripheral nerve blocks for anesthesia and postoperative analgesia has increased significantly in recent years. Adjuvants are frequently added to local anesthetics to prolong analgesia following peripheral nerve blockade. Numerous randomized controlled trials and meta-analyses have examined the pros and cons of the use of various individual adjuvants. OBJECTIVES: To systematically review adjuvant-related randomized controlled trials and meta analyses and provide clinical recommendations for the use of adjuvants in peripheral nerve blocks. METHODS: Randomized controlled trials and meta-analyses that were published between 1990 and 2014 were included in the initial bibliographic search, which was conducted using Medline/PubMed, Cochrane Central Register of Controlled Trials, and EMBASE. Only studies that were published in English and listed block analgesic duration as an outcome were included. Trials that had already been published in the identified meta-analyses and included adjuvants not in widespread use and published without an Investigational New Drug application or equivalent status were excluded. RESULTS: Sixty one novel clinical trials and meta-analyses were identified and included in this review. The clinical trials reported analgesic duration data for the following adjuvants: buprenorphine (6), morphine (6), fentanyl (10), epinephrine (3), clonidine (7), dexmedetomidine (7), dexamethasone (7), tramadol (8), and magnesium (4). Studies of perineural buprenorphine, clonidine, dexamethasone, dexmedetomidine, and magnesium most consistently demonstrated prolongation of peripheral nerve blocks. CONCLUSIONS: Buprenorphine, clonidine, dexamethasone, magnesium, and dexmedetomidine are promising agents for use in prolongation of local anesthetic peripheral nerve blocks, and further studies of safety and efficacy are merited. However, caution is recommended with use of any perineural adjuvant, as none have Food and Drug Administration approval, and concerns for side effects and potential toxicity persist. PMID- 26355601 TI - Asymmetric Hydroformylation of Heterocyclic Olefins Mediated by Supramolecularly Regulated Rhodium-Bisphosphite Complexes. AB - Rhodium complexes derived from conformationally transformable alpha,omega bisphosphite ligands combined with a suitable alkali metal BArF salt as a regulation agent (RA) provide high regio- and enantioselectivities in the asymmetric hydroformylation (AHF) of three heterocyclic olefins. The outcome of the AHF could be exquisitely regulated by choosing the appropriate RA with an increase in the ee, the reversal of the regioselectivity, or the complete suppression of one byproduct. PMID- 26355599 TI - A Novel Microtubule-Disrupting Agent Induces Endoplasmic Reticular Stress Mediated Cell Death in Human Hepatocellular Carcinoma Cells. AB - Here, we present evidence of a novel microtubule-disrupting agent, N-deacetyl-N (chromone-2-carbonyl)-thiocolchicine (TCD), exhibiting potent antitumor activity (with IC50 values in the nanomolar range) against hepatocellular carcinoma cell lines. Cell cycle analysis revealed that TCD induced G2/M cell-cycle arrest in a dose- and time-dependent manner in both Hep-J5 and Mahlavu HCC cell lines. TCD also induced a decrease in mitochondrial membrane potential (DeltaPsim) and caused DNA damage. Mechanistically, TCD activated protein kinase RNA-like endoplasmic reticular kinase and several transcription factors, including activating transcription factor (ATF) 6, ATF4, ATF3, and the CCAAT-enhancer binding protein homologous protein. These data clearly demonstrate that the antitumor activity of TCD is mechanistically linked to its capacity to trigger both intrinsic and extrinsic apoptotic cell death via endoplasmic reticular stress pathway. The potent antitumor activity of TCD was similarly demonstrated in a hepatocellular carcinoma xenograft model, where 5 and 10 mg/kg doses of TCD significantly arrested Hep-J5 and Mahlavu tumor growth. Our finding suggests that TCD is a promising therapeutic agent against hepatocellular carcinoma; further translational assessment of its clinical usage is warranted. PMID- 26355600 TI - Characterising the Profile of Everyday Executive Functioning and Relation to IQ in Adults with Williams Syndrome: Is the BRIEF Adult Version a Valid Rating Scale? AB - Although there is evidence of a distinct profile of executive dysfunction in Williams syndrome (WS), a rare genetically based neurodevelopmental disorder, the utility of informant reports of everyday executive function (EF) impairments and their relation to intelligence is not yet clear. Here we aimed to evaluate the functional impact of executive dysfunction in adults with WS and to establish the validity of child and adult versions of the most commonly used rating scale for EF assessment, the Behaviour Rating Inventory of Executive Function (BRIEF). We were also interested in whether distinct components of everyday EF relate to intelligence in WS. Parent report child (BRIEF-C) and adult (BRIEF-A) ratings were collected on 20 adults with WS (aged 18.5 to 53 years), with a mean IQ of 60.95 (SD = 17.67). Neuropsychological measures of EF included: The Shape School Test (Espy, 2007); select subdomains of EF from the Woodcock-Johnson III Tests of Cognitive Abilities, Australian Adaptation (WJ III COG); and select subdomains from the Vineland Adaptive Behaviour Scales, Second Edition-Parent Survey (Vineland-II). Results showed that the BRIEF-A, but not the BRIEF-C, was the most highly correlated with neuropsychological measures of EF, suggesting that it was a valid measure of the profile of EF impairments in adults with WS. The profile of everyday EF dysfunction revealed relative impairments in monitoring, working memory, planning and organisation in WS. In addition, both neuropsychological and rating scale measures showed an association between the shifting component of EF and intelligence. These findings indicate that the BRIEF-A is a valid measure of the multidimensional nature of real-world impairments in EF, and highlight its utility as a less labor intensive and low-cost screening tool for measuring specific EF impairments that could become the focus of targeted intervention in adults with WS. PMID- 26355602 TI - Diagnostic test accuracy: methods for systematic review and meta-analysis. AB - Systematic reviews are carried out to provide an answer to a clinical question based on all available evidence (published and unpublished), to critically appraise the quality of studies, and account for and explain variations between the results of studies. The Joanna Briggs Institute specializes in providing methodological guidance for the conduct of systematic reviews and has developed methods and guidance for reviewers conducting systematic reviews of studies of diagnostic test accuracy. Diagnostic tests are used to identify the presence or absence of a condition for the purpose of developing an appropriate treatment plan. Owing to demands for improvements in speed, cost, ease of performance, patient safety, and accuracy, new diagnostic tests are continuously developed, and there are often several tests available for the diagnosis of a particular condition. In order to provide the evidence necessary for clinicians and other healthcare professionals to make informed decisions regarding the optimum test to use, primary studies need to be carried out on the accuracy of diagnostic tests and the results of these studies synthesized through systematic review. The Joanna Briggs Institute and its international collaboration have updated, revised, and developed new guidance for systematic reviews, including systematic reviews of diagnostic test accuracy. This methodological article summarizes that guidance and provides detailed advice on the effective conduct of systematic reviews of diagnostic test accuracy. PMID- 26355603 TI - Fixed or random effects meta-analysis? Common methodological issues in systematic reviews of effectiveness. AB - Systematic review aims to systematically identify, critically appraise, and summarize all relevant studies that match predefined criteria and answer predefined questions. The most common type of systematic review is that assessing the effectiveness of an intervention or therapy. In this article, we discuss some of the common methodological issues that arise when conducting systematic reviews and meta-analyses of effectiveness data, including issues related to study designs, meta-analysis, and the use and interpretation of effect sizes. PMID- 26355605 TI - Co-assembly of cyclic peptide nanotubes and block copolymers in thin films: controlling the kinetic pathway. AB - Directed co-assembly of polymer-conjugated cyclic peptide nanotubes (CPNs) and block copolymers in thin films is a viable approach to fabricate sub-nanometer porous membranes without synthesizing nanotubes with identical length and vertical alignment. Here we show that the process is pathway dependent and successful co-assembly requires eliminating CPNs larger than 100 nm in solution. Optimizing polymer-solvent interactions can improve conjugate dispersion to a certain extent, but this limits thin film fabrication. Introduction of a trace amount of hydrogen-bond blockers, such as trifluoroacetic acid by vapor absorption, is more effective to reduce CPN aggregation in solution and circumvents issues of solvent immiscibility. This study provides critical insights into guided assemblies within nanoscopic frameworks toward sub-nanometer porous membranes. PMID- 26355604 TI - Effects of Menthol on Nicotine Pharmacokinetic, Pharmacology and Dependence in Mice. AB - Although menthol, a common flavoring additive to cigarettes, has been found to impact the addictive properties of nicotine cigarettes in smokers little is known about its pharmacological and molecular actions in the brain. Studies were undertaken to examine whether the systemic administration of menthol would modulate nicotine pharmacokinetics, acute pharmacological effects (antinociception and hypothermia) and withdrawal in male ICR mice. In addition, we examined changes in the brain levels of nicotinic receptors of rodents exposed to nicotine and menthol. Administration of i.p. menthol significantly decreased nicotine's clearance (2-fold decrease) and increased its AUC compared to i.p. vehicle treatment. In addition, menthol pretreatment prolonged the duration of nicotine-induced antinociception and hypothermia (2.5 mg/kg, s.c.) for periods up to 180 min post-nicotine administration. Repeated administration of menthol with nicotine increased the intensity of mecamylamine-precipitated withdrawal signs in mice exposed chronically to nicotine. The potentiation of withdrawal intensity by menthol was accompanied by a significant increase in nicotine plasma levels in these mice. Western blot analyses of alpha4 and beta2 nAChR subunit expression suggests that chronic menthol impacts the levels and distribution of these nicotinic subunits in various brain regions. In particular, co-administration of menthol and nicotine appears to promote significant increase in beta2 and alpha4 nAChR subunit expression in the hippocampus, prefrontal cortex and striatum of mice. Surprisingly, chronic injections of menthol alone to mice caused an upregulation of beta2 and alpha4 nAChR subunit levels in these brain regions. Because the addition of menthol to tobacco products has been suggested to augment their addictive potential, the current findings reveal several new pharmacological molecular adaptations that may contribute to its unique addictive profile. PMID- 26355606 TI - Electrochemotherapy (ECT) and irreversible electroporation (IRE) -advanced techniques for treating deep-seated tumors based on electroporation. PMID- 26355607 TI - Allometry of the Tendon Enthesis: Mechanisms of Load Transfer Between Tendon and Bone. AB - Several features of the tendon-to-bone attachment were examined allometrically to determine load transfer mechanisms. The humeral head diameter increased geometrically with animal mass. Area of the attachment site exhibited a near isometric increase with muscle physiological cross section. In contrast, the interfacial roughness as well as the mineral gradient width demonstrated a hypoallometric relationship with physiologic cross-sectional area (PCSA). The isometric increase in attachment area indicates that as muscle forces increase, the attachment area increases accordingly, thus maintaining a constant interfacial stress. Due to the presence of constant stresses at the attachment, the micrometer-scale features may not need to vary with increasing load. PMID- 26355608 TI - Infectious uveitis in Virginia. AB - PURPOSE: To report the causes, clinical features, and outcomes of infectious uveitis in patients managed in a mid-Atlantic tertiary care center. METHODS: Retrospective, observational study of infectious uveitis patients seen at the University of Virginia from 1984 to 2014. RESULTS: Seventy-seven of 491 patients (15.7%) were diagnosed with infectious uveitis (mean age 58 years, 71.4% female, 76.6% Caucasian). The mean follow-up was 5 years. Anterior uveitis was the most common anatomic classification (39 patients, 50.6%) followed by panuveitis (20 patients, 26.0%) and posterior uveitis (18 patients, 23.4%). The most common infectious etiology was herpetic anterior uveitis (37 patients, 48.1%) followed by toxoplasma uveitis (14 patients, 18.2%). The most prevalent viral pathogen was varicella-zoster virus (21 patients, 27.3%) followed by herpes simplex virus (20 patients, 26.0%). Acute retinal necrosis (ARN) was diagnosed in 14 patients (18.2%). Aqueous humor yielded an etiologic diagnosis in seven (50%) of ARN patients, four of whom tested positive for cytomegalovirus and three for varicella-zoster virus. On presentation, 43 patients (55.8%) had a visual acuity (VA) better than 20/40 and 17 (22.1%) had a VA worse than 20/200. VA at the final follow-up was better than 20/40 in 39 patients (50.6%) and worse than 20/200 in 22 patients (28.6%). In all, 16 (20.8%) and 10 (13.0%) patients required cataract and vitrectomy surgery, respectively. A total of 14 patients (18.2%) were on glaucoma topical treatment and four (5.2%) required glaucoma surgery. CONCLUSION: The most common type of infectious uveitis seen over the study period was herpetic anterior uveitis secondary to varicella-zoster virus or herpes simplex virus, found to be most prevalent in patients over 60 years of age. This finding is comparable to other American epidemiologic studies. Ocular toxoplasmosis and ARN were also common causes of infectious uveitis. In all, 50.6% of patients had a VA better than 20/40 at the final follow-up visit, indicating the importance of prompt referral and appropriate treatment. PMID- 26355609 TI - Botulinum Toxin-A Chemical Denervation for Platysmal Bands: Maximal Dosing Considerations. PMID- 26355610 TI - Voluma: A Systematic Review of Clinical Experience. AB - BACKGROUND: Dermal fillers are important for facial aesthetic enhancement as patients are favoring non-surgical procedures with minimal recovery time. Voluma is a volumizing hyaluronic acid filler, 20 mg/ml HA dermal filler, which was FDA approved in 2013 as the first dermal filler for treatment of age-related volume loss in the midface. OBJECTIVE: We sought to systematically review clinical studies and expert opinions of this 20 mg/ml HA dermal filler and to provide evidence-based recommendations and expert opinions. METHODS AND MATERIALS: A search of the computerized bibliographic databases Medline, Embase, Embal, Biosis, SciSearch, Pascal, HCAPlus, IPA, and Dissertation Abstracts was performed on August 18th 2014. RESULTS: Thirteen articles met inclusion and were included in our review: clinical trials with this 20 mg/ml HA dermal filler (10) and expert opinions and questionnaire survey studies of experts (3). This 20 mg/ml HA dermal filler has shown consistent, favorable results for treatment of age related facial volume loss, aesthetic enhancement, and HIV facial lipoatrophy. CONCLUSION: HA fillers are safe and effective with minimal recovery time and complications. Future studies with longer follow-up period and use of this 20 mg/ml HA dermal filler on areas other than midface may provide additional efficacy and safety outcomes. PMID- 26355611 TI - Effect of Midfacial Volume Augmentation With Non Animal Stabilized Hyaluronic Acid on the Nasolabial Fold and Global Aethestic Appearance. AB - INTRODUCTION: Non animal stabilized hyaluronic acid (Perlane, Galderma, SA) was FDA approved in 2007 for the treatment of facial wrinkles and folds. Off-label use led to the observation that injection of Perlane in the midface improved both global aesthetic appearance and reduced the depth of nasolabial folds. A proof-of concept trial was undertaken to explore this clinical observation further. METHODS: Twenty subjects with moderate midfacial volume loss and prominence of nasolabial folds underwent injection of the midface with Perlane between May and July, 2009. The average volume administered was 3.68 +/- 0.55 ml. Assessments were performed by the injecting physician and subject self-assessment for 6 months following treatment. RESULTS: 17 of 20 subjects completed all study visits. At the 6-month follow up visit 16 of 17 subjects were found to have clinically significant improvement of the midface and 14 of 17 subjects were found to have clinically significant improvement of the nasolabial folds. No serious adverse events occurred. CONCLUSION: In this early stage, proof-of concept trial, the majority of patients treated demonstrated clinically significant, aesthetically pleasing improvement 6 months after injection of Perlane in the midface. PMID- 26355612 TI - Calcium Hydroxylapatite for Augmentation of Face and Hands: A Retrospective Analysis in Italian Subjects. AB - To assess the use and safety of calcium hydroxylapatite for volume restoration of the face and hands in clinical practice, subjects from four Italian aesthetic clinics who had received calcium hydroxylapatite augmentation treatment between January 2012 and December 2013 were recruited. Records were retrospectively reviewed for demographic characteristics, number of treatments, area treated, injection depth and volume, method of administration, and adverse events. A total of 1,783 treatments were administered to 800 subjects (female: 93.5%; mean age: 49.6 years). Overall, 620 (77.5%) subjects were treated over two sessions for a particular indication, and 243 (30.3%) treated over three sessions. The most frequently treated areas were the zygomatic area (men: 30.2%; women: 30.6% of all treatments), malar area (24.5% and 24.3%), and marionette lines (18.9% and 11.6%). A cannula was used for most treatments (86.7%). Injection volume ranged from 0.4 mL to 1.5 mL. Injection-site swelling and bruising occurred with 18.2% and 11.3% of treatments, respectively. Most cases resolved within one week and two weeks, respectively. No serious/unexpected adverse events occurred. In clinical practice, calcium hydroxylapatite is a versatile, well-tolerated treatment for filling folds and volume restoration of the face and hands. PMID- 26355613 TI - Vismodegib for Locally Advanced Basal Cell Carcinoma: Descriptive Analysis of a Case Series and Comparison to the Literature. AB - OBJECTIVE: This case series explores the use of vismodegib to treat locally advanced basal cell carcinoma (laBCC), with a focus on tolerability, efficacy, and outcomes after treatment cessation. METHODS: Data from patients who underwent vismodegib treatment for laBCC at a single institution from 3/6/2012 through 3/15/2015 was utilized in this study. For all included cases, treatment responses as recorded at the first follow-up after treatment cessation were assessed and are reported as complete clinical response (CCR), partial clinical response (PCR), stable disease, or progressive disease. In cases of CCR, clinical disease free survival (DFS) was calculated as the time from cessation of vismodegib until last available follow-up, death, or recurrence. Data pertaining to side effects and adverse events was also recorded, and results are presented using descriptive statistics. RESULTS: A total of 24 patients and 31 tumors met inclusion criteria. CCR was observed in 17 of 31 tumors (55%), and 13 of 31 tumors (42%) demonstrated PCR. Stable disease was seen in one patient (one tumor) (3%). No cases demonstrated clinical tumor progression during treatment. The mean clinical DFS at time of data cut off for all cases of CCR was 9.3 months (range 2-21 months). In cases of PCR, the mean reduction in tumor size was 52% (range, 11%-80%). Only two patients (8%) discontinued treatment secondary to side effects. CONCLUSION: Each patient and each tumor responds uniquely to vismodegib treatment, including variable tumor responses and a wide range of side effects and tolerability. This study highlights important unique observations, and our data as a whole adds to previously published studies, leading to thought provoking questions. Overall, the FDA approval of vismodegib for advanced basal cell carcinoma has markedly improved the prognosis and care of affected patients. PMID- 26355614 TI - Azelaic Acid: Evidence-based Update on Mechanism of Action and Clinical Application. AB - Azelaic acid is a complex molecule with many diverse activities. The latter include anti-infective and anti-inflammatory action. The agent also inhibits follicular keratinization and epidermal melanogenesis. Due to the wide variety of biological activities, azelaic acid has been utilized as a management tool in a broad spectrum of disease states and cutaneous disorders. This paper reviews the clinical utility of azelaic acid, noting the quality of the evidence supporting each potential use. PMID- 26355615 TI - Efficacy and Tolerability of a Fixed Combination of Clindamycin Phosphate (1.2%) and Benzoyl Peroxide (3.75%) Aqueous Gel in Moderate and Severe Acne Vulgaris Subpopulations. AB - OBJECTIVE: To evaluate the efficacy, safety, and tolerability of a fixed combination clindamycin phosphate 1.2% and benzoyl peroxide 3.75% (clindamycin-BP 3.75%) aqueous gel in the treatment of moderate and severe acne. METHODS: Multicenter, double-blind study in 498 patients with moderate or severe acne randomized to clindamycin-BP 3.75% or vehicle, once-daily for 12 weeks. Efficacy evaluations included inflammatory and noninflammatory lesion counts and evaluator's global severity at baseline, and at weeks 4, 8, and 12. Adverse events (AEs) and tolerability were also assessed. This was a post hoc analysis of moderate and severe acne populations. RESULTS: Clindamycin-BP 3.75% significantly reduced inflammatory and noninflammatory lesions in both moderate and severe acne patients compared with vehicle. More than half of the patients with severe acne (55.1%) had at least a 2-grade reduction in evaluator's global severity score by week 12, and 30.6% of patients assessed their acne as 'clear' or 'almost clear'. Clindamycin-BP 3.75% was well tolerated, with no substantive differences from vehicle; and no patient discontinued due to AEs. CONCLUSIONS: Clindamycin-BP 3.75% aqueous gel is an effective and well-tolerated once-daily topical treatment for both moderate and severe acne. PMID- 26355616 TI - Effect of Carbon Dioxide Facial Therapy on Skin Oxygenation. AB - BACKGROUND: Recently popularized in the field of cosmetic dermatology, subcutaneous carbon dioxide (CO2) injections have been shown to improve the skin's appearance by augmenting oxygen delivery and thereby aiding cellular metabolism and neocollagenesis. However, they carry several risks and cannot be used on the entire face, leaving them best suited for the treatment of localized skin concerns. To combat these issues, a less invasive CO2 facial suited for full face treatment has been developed, though its efficacy in oxygenating the skin has not been thoroughly investigated. OBJECTIVE: The aim of this study was to evaluate the ability of the CO2 facial to oxygenate the skin. METHODS AND MATERIALS: Twelve patients were enrolled in this split-face study. They were treated one week apart with a CO2 facial on one side of the face and particle free microdermabrasion on the other. Measurements of transcutaneous oxygen tension (tcPO2) were recorded at baseline and after each treatment. Statistical significance was assessed by comparing the average tcPO2 difference in mmHg following microdermabrasion and after a carbon dioxide facial using a 1-tailed paired t-test (alpha = 0.05).
RESULTS: The average increase in tcPO2 after CO2 facial treatment was statistically significantly greater (p = .0252) than after microdermabrasion. CONCLUSION: Carbon dioxide facials improve skin oxygenation immediately following treatment, attributable to the generation of an artificial Bohr effect. PMID- 26355617 TI - Selective Non-contact Field Radiofrequency Extended Treatment Protocol: Evaluation of Safety and Efficacy. AB - BACKGROUND AND OBJECTIVE: Currently there are many non-invasive radiofrequency (RF) devices on the market that are utilized in the field of aesthetic medicine. At this time, there is only one FDA cleared device on the market that emits RF energy using a non-contact delivery system for circumferential reduction by means of adipocyte disruption. Innovation of treatment protocols is an integral part of aesthetic device development. However, when protocol modifications are made it is important to look at the safety as well as the potential for improved efficacy before initiating change. The purpose of this study was to evaluate the safety and efficacy of a newly designed extended treatment protocol using an operator independent selective non-contact RF device for the improvement in the contour and circumferential reduction of the abdomen and flanks (love handles). METHODS: Twenty-five subjects enrolled in the IRB approved multi-center study to receive four weekly 45-minute RF treatments to the abdomen and love handles. Standardized digital photographs and circumference measurements were taken at baseline and at the 1- and 3-month follow-up visits. Biometric measurements including weight, hydration and body fat were obtained at baseline and each study visit. A subset of 4 subjects were randomly selected to undergo baseline serum lipid and liver related blood tests with follow-up labs taken: 1 day post-treatment 1, 1 day post treatment 4, and at the 1- and 3-month follow-up visits. RESULTS: Twenty-four subjects (22 female, 2 male), average age of 47.9 years (30-69 years), completed the study. The data of the twenty-four subjects revealed a statistically significant change in circumference P<.001 with an average decrease in circumference of 4.22cm at the 3-month follow-up visit. Lab values for the subset of 4 subjects remained relatively unchanged with only minor fluctuations noted in the serum lipid values in two of the subjects. Three independent evaluators viewed pre-treatment and 3-month post treatment photographs to determine which photo was the after photo. The evaluators were able to correctly identify the post treatment photos with an 88% accuracy rate. Treatments were well tolerated by all subjects. No study related adverse events were reported. CONCLUSION: This study found that an extended treatment protocol using a selective RF device is a safe and effective method for the reduction of circumference and improved contouring of the abdomen and love handles. PMID- 26355618 TI - Comparative Effects of Sunscreens Alone vs Sunscreens Plus DNA Repair Enzymes in Patients With Actinic Keratosis: Clinical and Molecular Findings from a 6-Month, Randomized, Clinical Study. AB - Recent experimental irradiation studies have shown that the addition of DNA repair enzymes (photolyase and endonuclease) to traditional sunscreens may reduce ultraviolet radiation (UVR)-induced molecular damage to the skin to a greater extent than sunscreens alone. In this 6-month, randomized, clinical study, we sought to compare the clinical and molecular effects of sunscreens plus DNA repair enzymes vs. those of traditional sunscreens alone in patients with actinic keratosis (AK). A total of 28 AK patients were randomized to topically apply sunscreens plus DNA repair enzymes (enzyme group; n = 14) or sunscreens alone (sunscreen group; n = 14) for 6 months. The main outcome measures included 1) hyperkeratosis, 2) field cancerization (as measured by fluorescence diagnostics using methylaminolaevulinate), and 3) levels of cyclobutane pyrimidine dimers (CPDs) in skin biopsies. Both regimens produced a significant reduction of hyperkeratosis at 6 months, with no difference between the two groups. Field cancerization was significantly reduced by both regimens, but the decrease observed in the enzyme group was significantly more pronounced than in the sunscreen group (P < 0.001). At 6 months, CPDs decreased by 61% in the enzyme group and by 35% in the sunscreen group compared with baseline values (P < 0.001). These findings indicate that, despite a similar effect on hyperkeratosis, the addition of DNA repair enzymes to sunscreens was more effective in reducing field cancerization and CPDs than sunscreens alone. Taken together, our findings indicate that sunscreens plus DNA repair enzymes may be superior to traditional sunscreens alone in reducing field cancerization and UVR-associated molecular signatures (CPDs) in AK patients, potentially preventing malignant transformation into invasive squamous cell carcinoma in a more efficient manner. PMID- 26355619 TI - Assessment of a Comprehensive Anti-Aging Neck Cream. AB - INTRODUCTION: With many effective anti-aging solutions for the face, consumer focus is now turning to other parts of the body including the delicate skin on the neck. This study investigates the effect of a new neck cream on the appearance of texture, fine lines and wrinkles, laxity, and hydration. METHODS: 85 adult females ages 35-65 with Fitzpatrick skin types I through IV applied the test neck cream twice daily for a 3-month study period. Screening was conducted at Baseline, 2, 30, 60, and 90 days via a virtual trial. Subjects rated satisfaction in each of 4 anti-aging categories including hydration, texture, appearance of wrinkles, and appearance of laxity as well as three product attributes including application, feel, and smell. RESULTS: Improvement was statistically significant for all measured categories (hydration, texture, appearance of wrinkles, and appearance of laxity) with 94% of study subjects noting improvement in one or more of the measured categories. Further, the quantity of "Satisfied" and "Highly Satisfied" assessments increased 8-fold from baseline with a 94x increase in the quantity of "Highly Satisfied" assessments. DISCUSSION: The results demonstrate the product's rapid and continuing ability to improve the self-perceived signs of aging in the neck area including improvement in skin texture on the neck and a reduction in the appearance of wrinkles and laxity along the jawline. Future studies are recommended to determine the primary action mechanisms and to assess the degree of improvement by blinded physician assessment. PMID- 26355620 TI - Improvement in Atrophic Acne Scars Using Topical Synthetic Epidermal Growth Factor (EGF) Serum: A Pilot Study. AB - BACKGROUND: Atrophic acne scars are a common and psychologically devastating sequela of acne vulgaris that are refractory to the vast majority of topical treatments. OBJECTIVE: We evaluated the efficacy of a topically applied synthetic epidermal growth factor (EGF) serum in reducing the appearance of atrophic acne scars. METHODS: A single-center clinical trial was performed on nine self selected male and female patients with Goodman & Baron grade II-IV atrophic acne scars. Subjects followed a standardized treatment regimen, including twice-daily application of EGF serum to scarred areas over 12 weeks. Subject progress was evaluated at baseline and 4-week intervals by clinical photography, Investigator Global Assessment (IGA), Goodman grade and patient self-assessment. Final patient perceptions were shared by written self-assessment at the end of the study. Before and after photographs were also evaluated by a blind investigator. RESULTS: Eight subjects completed the trial. Compared to baseline, there was an improvement in mean IGA score from 2.875 (SEM= .327) to 2.38 (SEM = .375). Mean Goodman grade was reduced from 3.00 (SEM = .309) to 2.75 (SEM = .25). Of the eight pairs of before and after photographs given to a blind investigator, five were correctly chosen as the post-treatment image. Two were assessed as "excellent" (76-100%) improvement and three were assessed as "good" (50-75%) improvement. A one-tailed paired student t-test (alpha = .05) using blind investigator ratings of scar severity for each before and after photograph yielded a P-value of .0019, confirming the difference as statistically significant. On final self-assessment, all but one patient reported "good" to "excellent" improvement in their scars compared to baseline. 75% of patients who received alternative treatments in prior years reported EGF serum to be more efficacious. CONCLUSION: These results suggest that topical EGF may improve the appearance of atrophic acne scars, though further study and more objective evaluation measures are required for definitive conclusions to be drawn. PMID- 26355621 TI - Treatment of Alopecia Areata in the United States: A Retrospective Cross Sectional Study. AB - BACKGROUND: Alopecia Areata (AA) is a non-scarring alopecia that affects millions of Americans, however the way it is treated and which patients seek treatment is not well characterized. OBJECTIVE: To better understand how AA was being treated in the United States, what type of patients are seen for AA, and what physicians treated them. METHODS: We analyzed data from the National Ambulatory Medical Care Survey (NAMCS) and National Hospital Ambulatory Medical Care Survey (NHAMCS) from 2001 to 2010. We tabulated patient characteristics, the physicians who treated AA and what treatments were prescribed for AA. RESULTS: There were an estimated 2.6 million outpatient visits for AA. Patients with AA were most commonly treated by a dermatologists (84.8%). Patients were most commonly treated with topical and injected corticosteroids (61.0%) followed by minoxidil (5.9%) and topical tacrolimus (5.7%). Males made fewer visits per 1,000 capita compared to females (P=0.01). LIMITATIONS: The NAMCS and NHAMCS do not record severity of disease data. CONCLUSIONS: Topical and injected corticosteroids are the mainstay of treatment for AA, however the use of steroid sparing agents such as minoxidil is low. Despite no studies demonstrating efficacy, topical tacrolimus was used almost as frequently as minoxidil. PMID- 26355622 TI - Onychomycosis Diagnosis and Management: Perspectives from a Joint Dermatology Podiatry Roundtable. AB - Onychomycosis prevalence is expected to rise as the population ages and the prevalence of diabetes, peripheral vascular disease, and other significant risk factors rise. Until recently, treatment options were limited due to safety concerns with oral antifungals and low efficacy with available topical agents. Efinaconzole and tavaborole were approved by the FDA in 2014 for onychomycosis treatment and provide additional effective topical treatment options for patients with mild-to-moderate disease. Dermatologists and podiatrists both regularly treat onychomycosis, yet there are striking differences between specialties in approach to diagnosis and treatment. In order to explore these differences a joint dermatology-podiatry roundtable of onychomycosis experts was convened. Although it has little effect on mycologic cure, debridement may be a valuable adjunct to oral or topical antifungal therapy, especially in patients with greater symptom burden. However, few dermatologists incorporate debridement into their treatment plans and referral to podiatry may be appropriate for some of these patients. Furthermore, podiatrists may be better equipped to manage patients with concurrent diabetes or peripheral vascular disease and elderly patients who are unable to maintain proper foot hygiene. Once cure is achieved, lifestyle and hygiene practices, maintenance/prophylactic onychomycosis treatment, and proactive tinea pedis treatment in patients and family members may help to maintain patients' cured status. PMID- 26355623 TI - Men and Cosmetics: Social and Psychological Trends of an Emerging Demographic. AB - Though still accounting for a small fraction of all cosmetic procedures in the United States, men are an emerging and rapidly expanding demographic in the field of aesthetic medicine. In this article we highlight the trends contributing to the rise of male aesthetic procedures in dermatology, touching on social influences, psychological motivations, and treatment outcomes. PMID- 26355624 TI - Male Aesthetics: A Review of Facial Anatomy and Pertinent Clinical Implications. AB - Aesthetics continues to be a rapidly growing field within dermatology. In 2014, Americans spent 5 billion dollars on an estimated 9 million minimally invasive cosmetic procedures. Between 1997 and 2014, the number of aesthetic procedures performed on men increased by 273%. The approach to male aesthetics differs from that of females. Men have a squarer face, a more angled and larger jaw, and equally balanced upper and lower facial proportions. Facial muscle mass, subcutaneous tissue, and blood vessel density are also increased in men relative to women. While many of the same cosmetic procedures are performed in males and females, the approach, assessment, and treatment parameters are often different. Improper technique in a male patient can result in feminizing facial features and patient dissatisfaction. With an increasing number of men seeking aesthetic procedures, it behooves dermatologists to familiarize themselves with male facial anatomy and the practice of cosmetic dermatology in this population. PMID- 26355625 TI - Emerging Therapies for Androgenetic Alopecia. AB - Androgenetic alopecia is the progressive miniaturization of the scalp's terminal follicles in aging men. Over 40% of Caucasian men develop hair loss by the age of 40. Despite its prevalence, there are only two FDA approved medications to treat the condition. Recognizing the unmet need, new medical, procedural, and surgical treatments are being adopted to combat progressive hair loss. This review examines emerging hair loss treatments including medical therapies that the target prostaglandins, low level light therapy, platelet rich plasma injections, and robotic hair transplantation. PMID- 26355626 TI - Injectable Cosmetic Procedures for the Male Patient. AB - More than ever, male patients are seeking cosmetic procedures for a variety of reasons including but not limited to: a less aged appearance, social, or work related issues. Injectable neurotoxins and fillers are appealing to the male patient for their safety, rapid results, and minimal downtime. However, methods applied to the female patient do not always translate to the male patient. In this article, we review the anatomical, biological, and behavioral differences in men. We also provide an in-depth discussion of the techniques and dosages that are used in men, emphasizing the distinctions between the sexes. While once overlooked, this gender is becoming an important demographic in cosmetic dermatology. PMID- 26355627 TI - Male Body Contouring. AB - Men are increasingly turning to dermatologists and plastic surgeons to request procedures that correct or enhance physical features. With the advent of this emerging new patient population, alterations in preexisting aesthetic techniques, gender-specific uses of existing devices and overall approaches need to be revisited and adapted to obtain results that are suitable for the male patient. Recently, body contouring has become one of the most sought out procedures by men. Although the majority of clinical studies involving body contouring esthetics are performed with female patients, gains from such studies can be extrapolated to men. Body contouring can be broadly classified as non-invasive or invasive, depending on the modality used. Non-invasive contouring is most frequently performed with devices that target subcutaneous adipose with focused electrical or thermal energy, including low-level laser, cryolipolysis, ultrasonography, and radiofrequency. Invasive body contouring modalities useful for male body contouring include liposuction, pectoral and abdominal wall etching, jawline fillers, synthetic deoxycholic acid injections, and solid silicone implants. The purpose of this review is to bring attention to the unique aspects, strategies, and modalities used in aesthetic body contouring for the male patient. PMID- 26355628 TI - Laser and Light-Based Aesthetics in Men. AB - Men represent an important evolving segment of the cosmetic market. With the growing acceptability of cosmetic procedures along with societal and workplace pressure to maintain youthfulness, men increasingly seek the advice of aesthetic practitioners. Despite this so-called "Menaissance," there is a paucity of published literature regarding laser and light treatments of male skin. Herein the differences in male cutaneous physiology are addressed, followed by a review of light-based treatment of conditions largely unique to male skin, pseudofolliculitis barbae, and rhinophyma. Next, the publications related to laser treatment of male skin specifically are examined. We conclude with a discussion of personal observations derived from clinical experience with laser and light-based treatments in men. PMID- 26355629 TI - Treatment of Acne Scars With High Intensity Focused Radio Frequency. AB - In this multi-site case series, the efficacy of high intensity focused radiofrequency (RF) delivered to the dermis was evaluated for treating acne scars. A novel delivery system that uses insulated microneedles to deliver a desired thermal effect to multiple depths of the dermis while sparing the epidermis from RF injury was used. Four (4) healthy subjects from four different practices were evaluated and used in this case report. The subjects were treated between 3 or 4 times depending on the severity of the acne scars presented. The depth of thermal delivery was adjusted before each pass and all subjects received at a minimum, three passes to the treated area. Before and after photographs along with adverse effects were recorded. The theory behind the use of insulated needles with the active RF delivery at the distal tip is to allow for significant thermal injury to several layers of the dermis while avoiding thermal injury to the epidermis. This case report demonstrates significant improvement on acne scars and that all skin types should be safely treatable with minimum downtime realized. PMID- 26355630 TI - 2015 Arte Poster Competition First Place Winner: Assessing the Correlation Between Patient Anxiety and Satisfaction for Mohs Surgery. AB - Skin cancer and the surgical treatment thereof have the potential to be sources of great anxiety for patients. Examination of patient satisfaction, anxiety, and contributing factors has the potential to provide information surgeons can use to implement practices that have an impact on patient anxiety and satisfaction regarding dermatologic surgery. This study used a prospective interview to catalog patients' anxiety and experiences before and during the surgical process. Our results indicate that several pre- and perioperative factors have the potential to decrease a patient's overall anxiety. Notably, 33% of surgical patients reported a decrease in anxiety from the time of diagnosis until the day of surgery. Factors that contributed to this included a call discussing the diagnosis and what to expect on the day of surgery as well as reading written material or searching the internet for more information regarding the procedure. Furthermore, a call from the physician compared to a call from a nurse or other team member showed a greater effect on decreasing anxiety. During the surgical procedure, our results highlight several factors that can decrease a patient's anxiety. Most notably, eating, watching TV, bringing a guest, and engaging in small talk with surgeon and staff during the procedure subjectively decreased patients' anxiety. In summary, our results suggest that patients respond to a variety of factors to reduce anxiety and that each patient derives relief from anxiety in different manners. Therefore, offering a spectrum of comforting or distracting activities during the Mohs procedure is ideal and may reduce the need for pharmacologic anxiolytics. PMID- 26355631 TI - The Safety and Efficacy of a Sustainable Marine Extract for the Treatment of Thinning Hair: A Summary of New Clinical Research and Results from a Panel Discussion on the Problem of Thinning Hair and Current Treatments. AB - Alopecia and thinning hair are highly prevalent conditions affecting a large proportion of men and women. Diffused hair loss is often more difficult to diagnose in women, mostly due to over-reliance on the assumption of hormonal influences, and it is commonly treated with a multi-therapy approach. Clinical studies have demonstrated the effectiveness of a nutraceutical supplement to provide essential nutrients that aid in stimulating existing hair growth and reducing hair shedding. The supplement Viviscal(r) contains a proprietary blend of proteins, lipids, and glycosaminoglycans derived from sustainable marine sources. We present here a summary of studies that have examined the safety and efficacy of this nutraceutical; as well as discussions on hair loss and current therapies from a recently convened expert panel in dermatology and plastic surgery. PMID- 26355634 TI - Big Tobacco and Drugstore Chains: A Long, Cozy Relationship. PMID- 26355633 TI - A general class of recapture models based on the conditional capture probabilities. AB - We propose an Mhotb model for population size estimation in capture-recapture studies. The tb part is based on equality constraints for the conditional capture probabilities, leading to an extremely rich model class. Observed and unobserved heterogeneity are dealt with by means of a logistic parameterization. In order to explore the model class, we introduce a penalized version of the likelihood. The conditional likelihood and penalized conditional likelihood are maximized by means of efficient EM algorithms. Simulations and two real data examples illustrate the approach. PMID- 26355632 TI - Diagnosis of Liver Involvement in Primary Sjogren Syndrome. AB - Liver involvement was one of the first extraglandular manifestations to be reported in patients with primary Sjogren syndrome (SS). In the 1990s, a study of liver involvement in patients with primary SS integrated the evaluation of clinical signs of liver disease, liver function and a complete panel of autoantibodies. Recent developments in the field of hepatic and viral diseases have significantly changed the diagnostic approach to liver involvement in SS. The most recent studies have shown that, after eliminating hepatotoxic drugs and fatty liver disease, the two main causes of liver disease in primary SS are chronic viral infections and autoimmune liver diseases. The differential diagnosis of liver disease in primary SS (viral vs autoimmune) is clinically important, since the two processes require different therapeutic approaches and have different prognoses. With respect to viral infections, chronic HCV infection is the main cause of liver involvement in SS patients from the Mediterranean area, while chronic HBV infection may be the main cause of liver involvement in SS patients from Asian countries. After eliminating viral hepatitis, primary biliary cirrhosis (PBC) should be considered the main cause of liver disease in primary SS. PBC-related SS patients may have a broad spectrum of abnormalities of the liver, including having no clinical or analytical data suggestive of liver disease. Autoimmune hepatitis (AIH) is the second most frequently found autoimmune liver disease to be associated with SS (all reported cases are type I), and nearly 10% of these patients have an AIH-PBC overlap. Finally, IgG4 related disease must be investigated in patients with SS presenting with sclerosing cholangitis, especially when autoimmune pancreatitis or retroperitoneal fibrosis are also present. PMID- 26355635 TI - Sensitive Multiplexed Quantitative Analysis of Autoantibodies to Cancer Antigens with Chemically S-Cationized Full-Length and Water-Soluble Denatured Proteins. AB - Humoral immune responses against tumor-associated antigens (TAAs) or cancer/testis antigens (CTAs) aberrantly expressed in tumor cells are frequently observed in cancer patients. Recent clinical studies have elucidated that anticancer immune responses with increased levels of anti-TAA/CTA antibodies improve cancer survival rates. Thus, these antibody levels are promising biomarkers for diagnosing the efficiency of cancer immunotherapy. Full-length antigens are favored for detecting anti-TAA/CTA antibodies because candidate antigen proteins contain multiple epitopes throughout their structures. In this study, we developed a methodology to prepare purified water-soluble and full length antigens by using cysteine sulfhydryl group cationization (S cationization) chemistry. S-Cationized antigens can be prepared from bacterial inclusion bodies, and they exhibit improved protein solubility but preserved antigenicity. Anti-TAA/CTA antibodies detected in cancer patients appeared to recognize linear epitopes, as well as conformational epitopes, and because the frequency of cysteine side-residues on the epitope-paratope interface was low, any adverse effects of S-cationization were virtually negligible for antibody binding. Furthermore, S-cationized antigen-immobilized Luminex beads could be successfully used in highly sensitive quantitative-multiplexed assays. Indeed, patients with a more broadly induced serum anti-TAA/CTA antibody level showed improved progression-free survival after immunotherapy. The comprehensive anti TAA/CTA assay system, which uses S-cationized full-length and water-soluble recombinant antigens, may be a useful diagnostic tool for assessing the efficiency of cancer immunotherapy. PMID- 26355636 TI - Combined 2-deoxy glucose and metformin improves therapeutic efficacy of sodium iodide symporter-mediated targeted radioiodine therapy in breast cancer cells. AB - Radiosensitization using either metformin or 2-deoxy-d-glucose (2-DG) in various cancer cells has been reported. The present study reveals novel information on combining these drugs to enhance radiosensitization effect in breast cancer (BC) cells. Responses to low-dose Cobalt60 radiation, as well as a newly emerged radioiodine therapy target for BC, that is, sodium-iodide symporter (NIS or SLC5A5) protein, are tested. As therapeutic potential of NIS in BC is often limited due to low uptake and fast efflux rate of iodine, the scope of these two radiosensitizers to further improve NIS-mediated (131)I therapeutic efficacy is explored. Two BC cell lines, MCF-7, and MDA MB231 are tested to optimize minimal drug doses required for radiosensitization. A combination of 2 mM metformin and 20 mM 2-DG with 2 grey (Gy) Cobalt60 radiation shows significant radiosensitization effect (P=0.0002). In cells treated with the combination therapy, increased gammaH2A.X foci formation was noted. Further, MCF-7 BC cells overexpressing NIS (MCF-7 NIS) was established, and using the optimized drug concentrations, significant radiosensitization (P=0.0019) by 50 MU Ci (131)I usage was found to be the case as well. Apoptosis data corroborates with the result of clonogenic assay showing significant increase in apoptotic population upon dual drug-mediated radiosensitization. In case of metformin treatment, lowered adenosine triphosphate (ATP) content of the cell has been observed. The encouraging radiosensitization effect observed using combined 2-DG and metformin may aid in reducing Cobalt60 radiation exposure or for targeted radioiodine therapy in BC cells with NIS expression. This study indicates high potential of this drug combination in sensitizing BC cells for NIS-mediated-targeted radioiodine therapy, which otherwise may have lacked efficacy. PMID- 26355637 TI - Prevalence, management and outcomes of medically complex vulnerable elderly patients with urinary incontinence in the United States. AB - OBJECTIVES: To assess the prevalence, patient-physician communication, treatment and health outcomes associated with urinary incontinence (UI) among the medically complex vulnerable elderly (MCVE) in the United States (US). METHODS: Data from the 2006 to 2012 Medicare Health Outcomes Survey (HOS) were used. MCVE patients were aged 65+ years with a HOS VE score >= 3. UI was reported as a small, big or no problem. Descriptive statistics were used to assess patient-physician communication and treatment. Multivariable regression analyses were performed to assess the association of small or big UI problems with various outcomes. RESULTS: The annual UI prevalence increased among MCVE [from 35.8% (2006) to 38.6% (2012)]. MCVE with big UI problems communicated with their physicians more often than those with small UI problems (77.9% and 49.6%, respectively); however, treatment of UI remained low (48.5% and 29.1%, respectively). Physical component summary (PCS) and mental component summary (MCS) scores were lower among MCVE with small or big UI problems compared with those with no UI problems, respectively. The decrements in PCS and MCS scores associated with big UI problems were greater than the decrements associated with any of the other assessed conditions. MCVE with small or big UI problems, respectively, were more likely to report past falls, depression and activity daily living limitations vs. those without UI. The odds of having experienced these outcomes were greater for those with big UI vs. small UI problems. CONCLUSIONS: Urinary incontinence prevalence in the USA increased among MCVE from 2006 to 2012, although treatment of UI remained low. UI problems, particularly big UI problems, adversely impact health outcomes. Efforts to better identify and manage UI among the MCVE are needed. PMID- 26355638 TI - High-intensity resistance training attenuates dexamethasone-induced muscle atrophy. AB - INTRODUCTION: In this study we investigated the effects of high-intensity resistance training (RT) on dexamethasone (DEX)-induced muscle atrophy in flexor hallucis longus (FHL), tibialis anterior (TA), and soleus (SOL) muscles. METHODS: Rats underwent either high-intensity RT or were kept sedentary. In the last 10 days they received either DEX (0.5 mg/kg/day, intraperitoneally) or saline. RESULTS: DEX reduced body weight (-21%), food intake (-28%), FHL and TA muscle mass (-20% and -18%, respectively), and increased muscle-specific ring finger 1 (MuRF-1) protein level (+37% and +45.5%). RT attenuated FHL muscle atrophy through a combination of low increase in MuRF-1 protein level (-3.5%) and significant increases in mammalian target of rapamycin (mTOR) (+63%) and p70S6K (+46% and +49% for control and DEX, respectively) protein levels. CONCLUSION: RT attenuated DEX-induced muscle atrophy through a combination of increases in mTOR and p70S6K protein levels and a low increase in MuRF-1 protein level. PMID- 26355639 TI - Abundance of phosphorylated Apis mellifera CREB in the honeybee's mushroom body inner compact cells varies with age. AB - Hymenopteran eusociality has been proposed to be associated with the activity of the transcription factor CREB (cAMP-response element binding protein). The honeybee (Apis mellifera) is a eusocial insect displaying a pronounced age dependent division of labor. In honeybee brains, CREB-dependent genes are regulated in an age-dependent manner, indicating that there might be a role for neuronal honeybee CREB (Apis mellifera CREB, or AmCREB) in the bee's division of labor. In this study, we further explore this hypothesis by asking where in the honeybee brain AmCREB-dependent processes might take place and whether they vary with age in these brain regions. CREB is activated following phosphorylation at a conserved serine residue. An increase of phosphorylated CREB is therefore regarded as an indicator of CREB-dependent transcriptional activation. Thus, we here examine the localization of phosphorylated AmCREB (pAmCREB) in the brain and its age-dependent variability. We report prominent pAmCREB staining in a subpopulation of intrinsic neurons of the mushroom bodies. In these neurons, the inner compact cells (IC), pAmCREB is located in the nuclei, axons, and dendrites. In the central bee brain, the IC somata and their dendritic region, we observed an age-dependent increase of pAmCREB. Our results demonstrate the IC to be candidate neurons involved in age-dependent division of labor. We hypothesize that the IC display a high level of CREB-dependent transcription that might be related to neuronal and behavioral plasticity underlying a bee's foraging behavior. PMID- 26355640 TI - Nerve regeneration in chitosan conduits and in autologous nerve grafts in healthy and in type 2 diabetic Goto-Kakizaki rats. AB - Knowledge about nerve regeneration after nerve injury and reconstruction in appropriate diabetic animal models is incomplete. Short-term nerve regeneration after reconstruction of a 10-mm sciatic nerve defect with either a hollow chitosan conduit or an autologous nerve graft was investigated in healthy Wistar and diabetic Goto-Kakizaki (GK) rats. After 21 days, axonal outgrowth, the presence of activated and apoptotic Schwann cells and the thickness of the formed matrix in the conduits were measured. In general, nerve regeneration was superior in autologous nerve grafts. In chitosan conduits, a matrix, which was thicker in diabetic rats, was formed and was positively correlated with length of axonal outgrowth. Axonal outgrowth in conduits and in nerve grafts extended further in diabetic rats than in healthy rats. There was a higher percentage of activating transcription factor 3 (ATF3)-immunostained cells in nerve segments from healthy rats than in diabetic rats after autologous nerve graft reconstruction. In chitosan conduits, more cleaved caspase 3-stained Schwann cells were generally observed in the matrix from the diabetic rats than in healthy rats. However, there were fewer apoptotic cells in the distal segment in diabetic rats reconstructed with a chitosan conduit. Preoperative glucose levels were positively correlated with axonal outgrowth after both reconstruction methods. Axonal regeneration was better in autologous nerve grafts than in hollow chitosan conduits and was enhanced in diabetic GK rats compared to healthy rats after reconstruction. This study provides insights into the nerve regeneration process in a clinically relevant diabetic animal model. PMID- 26355641 TI - A prospective multicentre observational study of Permacol collagen paste for anorectal fistula: preliminary results. AB - AIM: Permacol collagen paste (Permacol paste) is a new option for the treatment of anorectal fistula. It functions by filling the fistula tract with an acellular crosslinked porcine dermal collagen matrix suspension. The MASERATI 100 study group was set up to evaluate the clinical outcome of Permacol paste in the treatment of anorectal fistula. This paper reports the results from the initial 30 patients enrolled in the MASERATI 100 prospective, observational clinical trial. METHOD: Patients (N = 30) with anal fistula presenting to 10 European academic surgical units were treated with a sphincter-preserving technique using Permacol paste. Fistula healing was assessed at 1, 3, 6 and 12 months after treatment, with the primary end-point of fistula healing at 6 months post surgery. Faecal continence and patient satisfaction were recorded at each follow up visit and adverse events were monitored throughout the follow-up. RESULTS: Of the 28 patients with data at 6 months post-surgery, 15 (54%) were healed, and the healing rate was maintained at 12 months. Healing after treatment with Permacol paste was similar for intersphincteric to transsphincteric fistulae and primary or recurrent fistulae. Only one patient exhibited an adverse event (perianal abscess) that was possibly related to the treatment. At the last outpatient visit, over 60% of patients were satisfied or very satisfied with the operation. CONCLUSION: Permacol paste is shown to be effective in treating primary and recurrent cryptoglandular anorectal fistula with minimal unwanted side effects. PMID- 26355643 TI - Circulating tumor cells are correlated with disease progression and treatment response in an orthotopic hepatocellular carcinoma model. AB - Hepatocellular carcinoma (HCC) is a highly malignant tumor characterized by rapid progression, poor prognosis, and frequent hematogenous metastasis. A minimally invasive diagnostic biomarker that can predict disease progression and treatment response would be of extraordinary benefit. Therefore, we have investigated whether the number of circulating tumor cells (CTCs) is correlated with disease progression and treatment response in HCC. Here we report that the number of CTCs, monitored by in vivo flow cytometry (IVFC), is strongly correlated with disease progression and treatment response in a highly metastatic orthotopic nude mouse model of green fluorescent protein (GFP)-labeled HCC. Sorafenib treatment reduces the number of CTCs significantly. The decreased number of CTCs is consistent with low lung metastasis. This study has demonstrated a considerable clinical value of CTCs as a biomarker in predicting disease progression and monitoring therapeutic efficacy in patients with HCC. PMID- 26355644 TI - Antimicrobial Resistance of Faecal Escherichia coli Isolates from Pig Farms with Different Durations of In-feed Antimicrobial Use. AB - Antimicrobial use and resistance in animal and food production are of concern to public health. The primary aims of this study were to determine the frequency of resistance to 12 antimicrobials in Escherichia coli isolates from 39 pig farms and to identify patterns of antimicrobial use on these farms. Further aims were to determine whether a categorization of farms based on the duration of in-feed antimicrobial use (long-term versus short-term) could predict the occurrence of resistance on these farms and to identify the usage of specific antimicrobial drugs associated with the occurrence of resistance. Escherichia coli were isolated from all production stages on these farms; susceptibility testing was carried out against a panel of antimicrobials. Antimicrobial prescribing data were collected, and farms were categorized as long term or short term based on these. Resistance frequencies and antimicrobial use were tabulated. Logistic regression models of resistance to each antimicrobial were constructed with stage of production, duration of antimicrobial use and the use of 5 antimicrobial classes included as explanatory variables in each model. The greatest frequencies of resistance were observed to tetracycline, trimethoprim/sulphamethoxazole and streptomycin with the highest levels of resistance observed in isolates from first-stage weaned pigs. Differences in the types of antimicrobial drugs used were noted between long-term and short-term use farms. Categorization of farms as long- or short-term use was sufficient to predict the likely occurrence of resistance to 3 antimicrobial classes and could provide an aid in the control of resistance in the food chain. Stage of production was a significant predictor variable in all models of resistance constructed and did not solely reflect antimicrobial use at each stage. Cross-selection and co-selection for resistance was evident in the models constructed, and the use of trimethoprim/sulphonamide drugs in particular was associated with the occurrence of resistance to other antimicrobials. PMID- 26355642 TI - SOCE and cancer: Recent progress and new perspectives. AB - Ca(2+) acts as a universal and versatile second messenger in the regulation of a myriad of biological processes, including cell proliferation, differentiation, migration and apoptosis. Store-operated Ca(2+) entry (SOCE) mediated by ORAI and the stromal interaction molecule (STIM) constitutes one of the major routes of calcium entry in nonexcitable cells, in which the depletion of intracellular Ca(2+) stores triggers activation of the endoplasmic reticulum (ER)-resident Ca(2+) sensor protein STIM to gate and open the ORAI Ca(2+) channels in the plasma membrane (PM). Accumulating evidence indicates that SOCE plays critical roles in cancer cell proliferation, metastasis and tumor neovascularization, as well as in antitumor immunity. We summarize herein the recent advances in our understanding of the function of SOCE in various types of tumor cells, vascular endothelial cells and cells of the immune system. Finally, the therapeutic potential of SOCE inhibitors in the treatment of cancer is also discussed. PMID- 26355645 TI - Coamplification of Myc/Pvt1 and homozygous deletion of Nlrp1 locus are frequent genetics changes in mouse osteosarcoma. AB - Osteosarcomas (OSs) are characterized by high levels of genomic instability (GI). To gain insights into the GI and its contribution toward understanding the genetic basis of OS, we characterized 19 primary and 13 metastatic mouse tumors in a genetically engineered novel mouse model of OS by a combination of genomic techniques. Through the bone-specific deletion of the wild-type Trp53 locus or activation of a metastatic-promoting missense R172Hp53 allele, C57BL/6 mice developed either localized or metastatic OS. Subsequent tumors were isolated and primary cultures created from primary bone and/or distal metastatic lesions, for example, lung and liver. These tumors exhibited high levels of GI with complex chromosomal rearrangements, amplifications, and deletions comparable to human OS. The combined genomic approaches identified frequent amplification of chromosome 15D1 and loss of 11B4 by CGH and/or SKY. Both 15D1 and 11B4 have homology with frequently altered chromosomal bands 8q24 and 17p13 in human OS, respectively. Subsequent array CGH, FISH, and qRT-PCR analysis identified coamplification and overexpression of Myc/Pvt1 transcripts from the 15D1 amplicon and loss and decreased expression of the Nlrp1b from 11B4. The Nlrp1 gene is the key mediator of apoptosis and interacts strongly with caspase 2. PMID- 26355646 TI - Can virtual reality exposure therapy gains be generalized to real-life? A meta analysis of studies applying behavioral assessments. AB - In virtual reality exposure therapy (VRET), patients are exposed to virtual environments that resemble feared real-life situations. The aim of the current study was to assess the extent to which VRET gains can be observed in real-life situations. We conducted a meta-analysis of clinical trials applying VRET to specific phobias and measuring treatment outcome by means of behavioral laboratory tests or recordings of behavioral activities in real-life. Data sources were searches of databases (Medline, PsycInfo, and Cochrane). We included in total 14 clinical trials on specific phobias. Results revealed that patients undergoing VRET did significantly better on behavioral assessments following treatment than before treatment, with an aggregated uncontrolled effect size of g = 1.23. Furthermore, patients undergoing VRET performed better on behavioral assessments at post-treatment than patients on wait-list (g = 1.41). Additionally, results of behavioral assessment at post-treatment and at follow-up revealed no significant differences between VRET and exposure in vivo (g = -0.09 and 0.53, respectively). Finally, behavioral measurement effect sizes were similar to those calculated from self-report measures. The findings demonstrate that VRET can produce significant behavior change in real-life situations and support its application in treating specific phobias. PMID- 26355647 TI - Central load reduces peripheral processing: Evidence from incidental memory of background speech. AB - Is there a trade-off between central (working memory) load and peripheral (perceptual) processing? To address this question, participants were requested to undertake an n-back task in one of two levels of central/cognitive load (i.e., 1 back or 2-back) in the presence of a to-be-ignored story presented via headphones. Participants were told to ignore the background story, but they were given a surprise memory test of what had been said in the background story, immediately after the n-back task was completed. Memory was poorer in the high central load (2-back) condition in comparison with the low central load (1-back) condition. Hence, when people compensate for higher central load, by increasing attentional engagement, peripheral processing is constrained. Moreover, participants with high working memory capacity (WMC) - with a superior ability for attentional engagement - remembered less of the background story, but only in the low central load condition. Taken together, peripheral processing - as indexed by incidental memory of background speech - is constrained when task engagement is high. PMID- 26355648 TI - Relations of fine-root morphology on (137)Cs uptake by fourteen Brassica species. AB - Fourteen Brassica species consisting of seven leafy vegetables and seven root vegetables were examined for (137)Cs uptake differences in relation to their fine root morphological characters. A pot experiment was conducted from November 2014 to February 2015 in a Phytroton using a contaminated soil of Fukushima prefecture. Leafy vegetables showed bigger root diameters, larger root surface area and larger root volume. Consequently, leafy vegetables had higher (137)Cs uptake compared to root vegetables. Among the three fine-root parameters, only root surface area was observed as a significant contributing factor to higher (137)Cs uptake in terms of transfer factor (TF, dry weight basis). Kakina exhibited higher (137)Cs TF value (0.20) followed by Chinese cabbage (0.18) and mizuna (0.17). Lower TF values were observed in turnip (0.059), rutabaga (Kitanoshou) (0.062) and radish (Ha daikon) (0.064). PMID- 26355649 TI - Effect of H bond removal and changes in the position of the iron-sulphur head domain on the spin-lattice relaxation properties of the [2Fe-2S](2+) Rieske cluster in cytochrome bc(1). AB - Here, comparative electron spin-lattice relaxation studies of the 2Fe-2S iron sulphur (Fe-S) cluster embedded in a large membrane protein complex - cytochrome bc1 - are reported. Structural modifications of the local environment alone (mutations S158A and Y160W removing specific H bonds between Fe-S and amino acid side chains) or in combination with changes in global protein conformation (mutations/inhibitors changing the position of the Fe-S binding domain within the protein complex) resulted in different redox potentials as well as g-, g-strain and the relaxation rates (T1(-1)) for the Fe-S cluster. The relaxation rates for T < 25 K were measured directly by inversion recovery, while for T > 60 K they were deduced from simulation of continuous wave EPR spectra of the cluster using a model that included anisotropy of Lorentzian broadening. In all cases, the relaxation rate involved contributions from direct, second-order Raman and Orbach processes, each dominating over different temperature ranges. The analysis of T1( 1) (T) over the range 5-120 K yielded the values of the Orbach energy (EOrb), Debye temperature thetaD and Raman process efficiency CRam for each variant of the protein. As the Orbach energy was generally higher for mutants S158A and Y160W, compared to wild-type protein (WT), it is suggested that H bond removal influences the geometry leading to increased strength of antiferromagnetic coupling between two Fe ions of the cluster. While thetaD was similar for all variants (~107 K), the efficiency of the Raman process generally depends on the spin-orbit coupling that is lower for S158A and Y160W mutants, when compared to the WT. However, in several cases CRam did not only correlate with spin-orbit coupling but was also influenced by other factors - possibly the modification of protein rigidity and therefore the vibrational modes around the Fe-S cluster that change upon the movement of the iron-sulphur head domain. PMID- 26355652 TI - Antiviral Therapy of Liver Cirrhosis Related to Hepatitis B Virus Infection. AB - Hepatitis B virus (HBV) infection is a leading cause of liver disease worldwide, with 75% of those affected distributed in the Asia-Pacific region. Approximately one million HBV-infected patients die of liver cirrhosis and hepatocellular carcinoma (HCC) each year. If left untreated, 6-20% of chronic hepatitis B (CHB) patients will develop cirrhosis over five years. The cumulative incidence of HBV related cirrhosis, disease progression, and prognosis are closely associated with serum HBV DNA levels. Antiviral therapy in HBV-related cirrhosis has been documented by several long-term cohort studies to decrease disease progression to hepatic decompensation and HCC. The approval and availability of oral antiviral agents with better safety profiles has greatly improved the prognosis for HBV related cirrhosis. Here, we discuss the significance of antiviral therapy for HBV related cirrhosis and the management of HBV-related diseases in the future. PMID- 26355653 TI - Harmonization of QSAR Best Practices and Molecular Docking Provides an Efficient Virtual Screening Tool for Discovering New G-Quadruplex Ligands. AB - Telomeres and telomerase are key players in tumorogenesis. Among the various strategies proposed for telomerase inhibition or telomere uncapping, the stabilization of telomeric G-quadruplex (G4) structures is a very promising one. Additionally, G4 stabilizing ligands also act over tumors mediated by the alternative elongation of telomeres. Accordingly, the discovery of novel compounds able to act on telomeres and/or inhibit the telomerase enzyme by stabilizing DNA telomeric G4 structures as well as the development of approaches efficiently prioritizing such compounds constitute active areas of research in computational medicinal chemistry and anticancer drug discovery. In this direction, we applied a virtual screening strategy based on the rigorous application of QSAR best practices and its harmonized integration with structure based methods. More than 600,000 compounds from commercial databases were screened, the first 99 compounds were prioritized, and 21 commercially available and structurally diverse candidates were purchased and submitted to experimental assays. Such strategy proved to be highly efficient in the prioritization of G4 stabilizer hits, with a hit rate of 23.5%. The best G4 stabilizer hit found exhibited a shift in melting temperature from FRET assay of +7.3 degrees C at 5 MUM, while three other candidates also exhibited a promising stabilizing profile. The two most promising candidates also exhibited a good telomerase inhibitory ability and a mild inhibition of HeLa cells growth. None of these candidates showed antiproliferative effects in normal fibroblasts. Finally, the proposed virtual screening strategy proved to be a practical and reliable tool for the discovery of novel G4 ligands which can be used as starting points of further optimization campaigns. PMID- 26355654 TI - Bioactive glass-reinforced bioceramic ink writing scaffolds: sintering, microstructure and mechanical behavior. AB - The densification of pore struts in bioceramic scaffolds is important for structure stability and strength reliability. An advantage of ceramic ink writing is the precise control over the microstructure and macroarchitecture. However, the use of organic binder in such ink writing process would heavily affect the densification of ceramic struts and sacrifice the mechanical strength of porous scaffolds after sintering. This study presents a low-melt-point bioactive glass (BG)-assisted sintering strategy to overcome the main limitations of direct ink writing (extrusion-based three-dimensional printing) and to produce high-strength calcium silicate (CSi) bioceramic scaffolds. The 1% BG-added CSi (CSi-BG1) scaffolds with rectangular pore morphology sintered at 1080 degrees C have a very small BG content, readily induce apatite formation, and show appreciable linear shrinkage (~21%), which is consistent with the composite scaffolds with less or more BG contents sintered at either the same or a higher temperature. These CSi-BG1 scaffolds also possess a high elastic modulus (~350 MPa) and appreciable compressive strength (~48 MPa), and show significant strength enhancement after exposure to simulated body fluid-a performance markedly superior to those of pure CSi scaffolds. Particularly, the honeycomb-pore CSi-BG1 scaffolds show markedly higher compressive strength (~88 MPa) than the scaffolds with rectangular, parallelogram, and Archimedean chord pore structures. It is suggested that this approach can potentially facilitate the translation of ceramic ink writing and BG-assisted sintering of bioceramic scaffold technologies to the in situ bone repair. PMID- 26355655 TI - An explanation of the relationship between mass, metabolic rate and characteristic length for placental mammals. AB - The Mass, Metabolism and Length Explanation (MMLE) was advanced in 1984 to explain the relationship between metabolic rate and body mass for birds and mammals. This paper reports on a modernized version of MMLE. MMLE deterministically computes the absolute value of Basal Metabolic Rate (BMR) and body mass for individual animals. MMLE is thus distinct from other examinations of these topics that use species-averaged data to estimate the parameters in a statistically best fit power law relationship such as BMR = a(bodymass) (b) . Beginning with the proposition that BMR is proportional to the number of mitochondria in an animal, two primary equations are derived that compute BMR and body mass as functions of an individual animal's characteristic length and sturdiness factor. The characteristic length is a measureable skeletal length associated with an animal's means of propulsion. The sturdiness factor expresses how sturdy or gracile an animal is. Eight other parameters occur in the equations that vary little among animals in the same phylogenetic group. The present paper modernizes MMLE by explicitly treating Froude and Strouhal dynamic similarity of mammals' skeletal musculature, revising the treatment of BMR and using new data to estimate numerical values for the parameters that occur in the equations. A mass and length data set with 575 entries from the orders Rodentia, Chiroptera, Artiodactyla, Carnivora, Perissodactyla and Proboscidea is used. A BMR and mass data set with 436 entries from the orders Rodentia, Chiroptera, Artiodactyla and Carnivora is also used. With the estimated parameter values MMLE can calculate characteristic length and sturdiness factor values so that every BMR and mass datum from the BMR and mass data set can be computed exactly. Furthermore MMLE can calculate characteristic length and sturdiness factor values so that every body mass and length datum from the mass and length data set can be computed exactly. Whether or not MMLE can calculate a sturdiness factor value so that an individual animal's BMR and body mass can be simultaneously computed given its characteristic length awaits analysis of a data set that simultaneously reports all three of these items for individual animals. However for many of the addressed MMLE homogeneous groups, MMLE can predict the exponent obtained by regression analysis of the BMR and mass data using the exponent obtained by regression analysis of the mass and length data. This argues that MMLE may be able to accurately simultaneously compute BMR and mass for an individual animal. PMID- 26355656 TI - The effect of neuromuscular electrical stimulation on functional status and quality of life after knee arthroplasty: a randomized controlled study. AB - [Purpose] The aim of this study was to investigate the effect of the addition of NMES to the post-TKA rehabilitation protocol on the functional status and quality of life of the patients. [Subjects and Methods] Patients were randomized into an exercise (control) and electrical stimulation (NMES) group. A home exercise program was prescribed for the control group. For the neuromuscular stimulation group 30 minute electrical stimulation applied to the vastus medialis muscle 5 days a week for 4 to 6 weeks. VAS, the timed up and go test, WOMAC and SF-36 scores were evaluated preoperatively and postoperatively at the first month and the third month of the follow-up period. [Results] Both the NMES group had 30 patients each, with 2 and 1 male patients respectively. The comparisons of WOMAC results at month 1 revealed that pain, stiffness, and total scores of the NMES group was significantly better than those of control group at the first and third months. Significantly better physical function and SF-36 subscales, except mental health, were found for the NMES group at the first month of follow-up. [Conclusion] The inclusion of the neuromuscular electrical stimulation program after knee arthroplasty was more effective at providing rapid improvements in knee pain, walking distance and quality of life. PMID- 26355657 TI - Immunological Features and Clinical Benefits of Conjugate Vaccines against Bacteria. PMID- 26355658 TI - Inhibitory Effects of Cytosolic Ca(2+) Concentration by Ginsenoside Ro Are Dependent on Phosphorylation of IP3RI and Dephosphorylation of ERK in Human Platelets. AB - Intracellular Ca(2+) ([Ca(2+)] i ) is platelet aggregation-inducing molecule and is involved in activation of aggregation associated molecules. This study was carried out to understand the Ca(2+)-antagonistic effect of ginsenoside Ro (G Ro), an oleanane-type saponin in Panax ginseng. G-Ro, without affecting leakage of lactate dehydrogenase, dose-dependently inhibited thrombin-induced platelet aggregation, and the half maximal inhibitory concentration was approximately 155 MUM. G-Ro inhibited strongly thrombin-elevated [Ca(2+)] i , which was strongly increased by A-kinase inhibitor Rp-8-Br-cAMPS compared to G-kinase inhibitor Rp-8 Br-cGMPS. G-Ro increased the level of cAMP and subsequently elevated the phosphorylation of inositol 1, 4, 5-triphosphate receptor I (IP3RI) (Ser(1756)) to inhibit [Ca(2+)] i mobilization in thrombin-induced platelet aggregation. Phosphorylation of IP3RI (Ser(1756)) by G-Ro was decreased by PKA inhibitor Rp-8 Br-cAMPS. In addition, G-Ro inhibited thrombin-induced phosphorylation of ERK 2 (42 kDa), indicating inhibition of Ca(2+) influx across plasma membrane. We demonstrate that G-Ro upregulates cAMP-dependent IP3RI (Ser(1756)) phosphorylation and downregulates phosphorylation of ERK 2 (42 kDa) to decrease thrombin-elevated [Ca(2+)] i , which contributes to inhibition of ATP and serotonin release, and p-selectin expression. These results indicate that G-Ro in Panax ginseng is a beneficial novel Ca(2+)-antagonistic compound and may prevent platelet aggregation-mediated thrombotic disease. PMID- 26355659 TI - Notice to Readers: The Effect of Falsified Clostridium difficile Infections Surveillance Data on Results Reported in MMWR. AB - In 2012, MMWR published the report, "Vital Signs: Preventing Clostridium difficile Infections," which examined Clostridium difficile infection (CDI) surveillance data. This report contained several errors pertaining to Emerging Infections Program (EIP) data. These errors occurred as a result of scientific misconduct by a former employee of the Oregon Health Authority. The Public Health Service Office of Research Integrity has determined that the former employee falsified or fabricated data for 56 Oregon EIP CDI case report forms (https://ori.hhs.gov/content/case-summary-asherin-ryan). The authors re-analyzed the EIP data to determine if the removal of all Oregon CDI cases (57 total cases) from the 10,342 cases included in the original publication altered the previously reported results. It did not. Re-analysis confirms the conclusions in the original report. Data in the original report from sources other than the Oregon Health Authority (i.e., from other EIP sites, the National Healthcare Safety Network, and Illinois, Massachusetts, and New York CDI prevention programs) were not involved in the research misconduct.Errata for the 2012 report have been published in this issue of MMWR. PMID- 26355660 TI - Sheep deficient in vitamin E preferentially select for a feed with a higher concentration of vitamin E. AB - Given the capacity of ruminants to modify diet selection based on metabolic needs, we hypothesised that, when given a choice, lambs experiencing a vitamin E deficiency would consume more of a vitamin E-enriched feed than lambs not deficient in vitamin E. Fifty-six Dohne Merino lambs were divided into two groups and fed either a vitamin E-deficient diet over 40 days to induce low plasma vitamin E or a vitamin E-enriched diet to induce high plasma vitamin E. The lambs were then offered a choice of vitamin E-enriched and vitamin E-deficient pellets. For half of the animals, the enriched diet was paired with strawberry flavour and the deficient diet was paired with orange flavour, while the reverse pairings were offered to the others. Lamb preference for the diets was measured daily for the following 15 days. There was a three-way interaction between the high and low vitamin E treatment groups*vitamin E content and type of flavour in the feed*time (days). The lambs preferred pellets flavoured with strawberry but this preference changed to orange flavour in vitamin E-deficient lambs if the orange flavour was paired with high vitamin E. Lambs without a deficiency continued to prefer strawberry-flavoured pellets, regardless of the vitamin E concentrations in the pellets. It is possible that self-learning contributed to the low vitamin E group of lambs changing preference to orange flavour in order to consume more vitamin E, presumably to remediate the deficiency. PMID- 26355661 TI - Gene-environment interactions. PMID- 26355662 TI - Expanding the clinical, allelic, and locus heterogeneity of retinal dystrophies. AB - PURPOSE: Retinal dystrophies (RD) are heterogeneous hereditary disorders of the retina that are usually progressive in nature. The aim of this study was to clinically and molecularly characterize a large cohort of RD patients. METHODS: We have developed a next-generation sequencing assay that allows known RD genes to be sequenced simultaneously. We also performed mapping studies and exome sequencing on familial and on syndromic RD patients who tested negative on the panel. RESULTS: Our panel identified the likely causal mutation in >60% of the 292 RD families tested. Mapping studies on all 162 familial RD patients who tested negative on the panel identified two novel disease loci on Chr2:25,550,180 28,794,007 and Chr16:59,225,000-72,511,000. Whole-exome sequencing revealed the likely candidate as AGBL5 and CDH16, respectively. We also performed exome sequencing on negative syndromic RD cases and identified a novel homozygous truncating mutation in GNS in a family with the novel combination of mucopolysaccharidosis and RD. Moreover, we identified a homozygous truncating mutation in DNAJC17 in a family with an apparently novel syndrome of retinitis pigmentosa and hypogammaglobulinemia. CONCLUSION: Our study expands the clinical and allelic spectrum of known RD genes, and reveals AGBL5, CDH16, and DNAJC17 as novel disease candidates.Genet Med 18 6, 554-562. PMID- 26355663 TI - Predicting facial characteristics from complex polygenic variations. AB - Research into the importance of the human genome in the context of facial appearance is receiving increasing attention and has led to the detection of several Single Nucleotide Polymorphisms (SNPs) of importance. In this work we attempt a holistic approach predicting facial characteristics from genetic principal components across a population of 1266 individuals. For this we perform a genome-wide association analysis to select a large number of SNPs linked to specific facial traits, recode these to genetic principal components and then use these principal components as predictors for facial traits in a linear regression. We show in this proof-of-concept study for facial trait prediction from genome-wide SNP data that some facial characteristics can be modeled by genetic information: facial width, eyebrow width, distance between eyes, and features involving mouth shape are predicted with statistical significance (p<0.03). PMID- 26355665 TI - Concentration-Induced J-Aggregate Formation Causes a Biphasic Change in the Release of trans-Combretastatin A4 Disodium Phosphate from Archaeosomes and the Subsequent Cytotoxicity on Mammary Cancer Cells. AB - Combretastatin A4 disodium phosphate (CA4P) is a fluorescent, water-soluble prodrug able to induce vascular shutdown within tumors at doses less than one tenth of the maximum tolerated dose. As a continued effort to develop efficient liposomal CA4P to treat solid tumor, we herein investigate the physical and spectroscopic properties of CA4P in aqueous solution and the mechanism of CA4P release from archaeal tetraether liposomes (archaeosomes). We found that cis-CA4P can be photoisomerized to trans-CA4P. This photoisomerization results in an increase in fluorescence intensity. Both cis- and trans-CA4P undergo fluorescence intensity self-quenching after they reach a critical concentration Cq (~0.15-0.25 mM). Moreover, both cis- and trans-CA4P in buffer exhibit a red shift in their excitation spectrum and an increase in excitation spectrum band sharpness with increasing concentration, which can be attributed to the formation of J aggregates. The onset of the dramatic change in excitation maximum occurs at concentrations close to Cq, suggesting that the self-quenching arises from extensive J-aggregate formation and that, when CA4P concentration exceeds Cq, J aggregate formation begins to increase sharply. Our data also suggest that the extent of J-aggregate formation plays a critical role in CA4P release from tetraether archaeosomes and in the subsequent cytotoxicity on cultured human breast cancer MCF-7 cells. The drug leakage and cytotoxicity rate constants vary with the initial CA4P concentration entrapped inside archaeosomes in a biphasic manner, reaching a local maximum at 0.25-0.50 mM. A mechanism based on the concept of J-aggregate formation has been proposed to explain the biphasic changes in drug release and cytotoxicity with increasing drug concentration. Tetraether archaeosomes are extraordinarily stable and relatively nontoxic to animals; thus, they are promising nano drug carriers. The results obtained from this study pave the way for future development of archaeosomal CA4P to treat solid tumors. PMID- 26355664 TI - 52 additional reference population samples for the 55 AISNP panel. AB - Ancestry inference for a person using a panel of SNPs depends on the variation of frequencies of those SNPs around the world and the amount of reference data available for calculation/comparison. The Kidd Lab panel of 55 AISNPs has been incorporated in commercial kits by both Life Technologies and Illumina for massively parallel sequencing. Therefore, a larger set of reference populations will be useful for researchers using those kits. We have added reference population allele frequencies for 52 population samples to the 73 previously entered so that there are now allele frequencies publicly available in ALFRED and FROG-kb for a total of 125 population samples. PMID- 26355666 TI - In Vitro Priming of Naive T-cells with p-Phenylenediamine and Bandrowski's Base. AB - p-Phenylenediamine (PPD) is a component of hair dye formulations that is associated with T-cell mediated allergic contact dermatitis. Antigen-specific T cells from allergic contact dermatitis patients are activated with either PPD or the oxidation product, Bandrowski's base. In nonallergic individuals, T-cells that are activated by Bandrowski's base, but not by PPD, are readily detectable. The aim of the current study was to use an in vitro T-cell priming assay to assess the activation of memory and naive T-cells from healthy donors with PPD and Bandrowski's base, and to compare these responses to those observed from allergic patients. Both PPD and Bandrowski's base-responsive clones were generated from allergic patients. The majority of Bandrowski's base-responsive clones were CD4+ and displayed a lack of PPD reactivity. In contrast, CD4+ and CD8+ clones displaying PPD reactivity were detected. Approximately 25% of these displayed low levels of reactivity to Bandrowski's base. Clones from the allergic patients secreted a range of cytokines including IFN-gamma, Il-13, and Il-22. In healthy donors, Bandrowski's base-specific T-cell proliferative responses and cytokine secretion were detected with both naive and memory T-cells. T-cell clones generated from the Bandrowski's base-responsive cultures responded to Bandrowski's base but not PPD. PPD-specific naive and memory T-cell responses were not detected from healthy donors. These data show that Bandrowski's base stimulates pre-existing memory T-cells isolated from healthy donors and primes naive T-cells when the chemical is bound to autologous dendritic cells. Priming naive T-cells against PPD failed, suggesting an important individual susceptibility factor is missing from the in vitro T-cell priming assay. PMID- 26355668 TI - Medical Students' Perceptions of Peer Assessment in a Problem-based Learning Curriculum. AB - OBJECTIVES: Peer assessment (PA) is believed to support learning and help students develop both professionally and personally. The aim of this study was to examine medical students' perceptions of intragroup PA in a problem-based learning (PBL) setting. METHODS: This study was carried out between September and November 2014 and involved six random groups of fourth-year undergraduate medical students (n = 60) enrolled at the Arabian Gulf University in Manama, Bahrain. While working on set tasks within a curriculum unit, each student evaluated a randomly selected peer using an English language adapted assessment tool to measure responsibility and respect, information processing, critical analysis, interaction and collaborative skills. At the end of the unit, students' perceptions of PA were identified using a specifically-designed voluntary and anonymous self-administered questionnaire in English. RESULTS: A total of 55 students participated in the study (response rate: 92%). The majority of students reported that their learning (60%), attendance (67%), respect towards group members (70%) and participation in group discussions (71%) improved as a result of PA. Regarding problem analysis skills, most participants believed that PA improved their ability to analyse problems (65%), identify learning needs (64%), fulfil tasks related to the analysis of learning needs (72%) and share knowledge within their group (74%). Lastly, a large proportion of students reported that this form of assessment helped them develop their communication (71%) and self assessment skills (73%), as well as collaborative abilities (75%). CONCLUSION: PA was well accepted by the students in this cohort and led to self-reported improvements in learning, skills, attitudes, engagement and other indicators of personal and professional development. PA was also perceived to have a positive impact on intragroup attitudes. PMID- 26355669 TI - Common Iliac Artery Thrombosis following Pelvic Surgery Resulting in Kidney Allograft Failure Successfully Treated by Percutaneous Transluminal Angioplasty with Balloon-Expandable Covered Stent. AB - We report the case of a 66-year-old woman who developed acute kidney allograft failure due to thrombotic occlusion of the common iliac artery after hysterectomy requiring emergent allograft rescue. She underwent percutaneous transluminal angioplasty with endovascular balloon expandable covered stent graft placement in the right common iliac artery. Although there are a handful of case reports of acute limb ischemia secondary to acute common iliac artery thrombosis, this is the first case reported in the literature resulting in successful kidney allograft rescue following pelvic surgery. PMID- 26355667 TI - Transfer of regulatory T cells into abortion-prone mice promotes the expansion of uterine mast cells and normalizes early pregnancy angiogenesis. AB - Implantation of the fertilized egg depends on the coordinated interplay of cells and molecules that prepare the uterus for this important event. In particular, regulatory T cells (Tregs) are key regulators as their ablation hinders implantation by rendering the uterus hostile for the embryo. In addition, the adoptive transfer of Tregs can avoid early abortion in mouse models. However, it is still not defined which mechanisms underlie Treg function during this early period. Cells of the innate immune system have been reported to support implantation, in part by promoting angiogenesis. In particular, uterine mast cells (uMCs) emerge as novel players at the fetal-maternal interface. Here, we studied whether the positive action of Tregs is based on the expansion of uMCs and the promotion of angiogenesis. We observed that abortion-prone mice have insufficient numbers of uMCs that could be corrected by the adoptive transfer of Tregs. This in turn positively influenced the remodeling of spiral arteries and placenta development as well as the levels of soluble fms-like tyrosine kinase 1 (sFlt-1). Our data suggest an interplay between Tregs and uMCs that is relevant for the changes required at the feto-maternal interface for the normal development of pregnancy. PMID- 26355670 TI - Regio-, Diastereo-, and Enantioselective Nitroso-Diels-Alder Reaction of 1,3 Diene-1-carbamates Catalyzed by Chiral Phosphoric Acids. AB - Chiral phosphoric acid-catalyzed asymmetric nitroso-Diels-Alder reaction of nitrosoarenes with carbamate-dienes afforded cis-3,6-disubstituted dihydro-1,2 oxazines in high yields with excellent regio-, diastereo-, and enantioselectivities. Interestingly, we observed that the catalyst is able not only to control the enantioselectivity but also to reverse the regioselectivity of the noncatalyzed nitroso-Diels-Alder reaction. The regiochemistry reversal and asynchronous concerted mechanism were confirmed by DFT calculations. PMID- 26355671 TI - Intra-rater reliability of hallux flexor strength measures using the Nintendo Wii Balance Board. AB - BACKGROUND: The purpose of this study was to investigate the intra-rater reliability of a new method in combination with the Nintendo Wii Balance Board (NWBB) to measure the strength of hallux flexor muscle. METHODS: Thirty healthy individuals (age: 34.9 +/- 12.9 years, height: 170.4 +/- 10.5 cm, weight: 69.3 +/ 15.3 kg, female = 15) participated. Repeated testing was completed within 7 days. Participants performed strength testing in sitting using a wooden platform in combination with the NWBB. This new method was set up to selectively recruit an intrinsic muscle of the foot, specifically the flexor hallucis brevis muscle. Statistical analysis was performed using intra-class coefficients and ordinary least product analysis. To estimate measurement error, standard error of measurement (SEM), minimal detectable change (MDC) and percentage error were calculated. RESULTS: Results indicate excellent intra-rater reliability (ICC = 0.982, CI = 0.96-0.99) with an absence of systematic bias. SEM, MDC and percentage error value were 0.5, 1.4 and 12 % respectively. CONCLUSIONS: This study demonstrates that a new method in combination with the NWBB application is reliable to measure hallux flexor strength and has potential to be used for future research and clinical application. PMID- 26355672 TI - In HIV-positive patients, myeloid-derived suppressor cells induce T-cell anergy by suppressing CD3zeta expression through ELF-1 inhibition. AB - OBJECTIVE: During HIV infection, a down-modulation of CD3zeta was found on T cells, contributing to T-cell anergy. In this work, we studied the correlation between myeloid-derived suppressor cells (MDSC) frequency and T-cell CD3zeta expression. Moreover, we investigated the mechanisms of CD3zeta decrease exploited by MDSC. DESIGN AND METHOD: CD3zeta expression and MDSC frequency were evaluated by flow cytometry on peripheral blood mononuclear cells from 105 HIV positive (HIV+) patients. The role of MDSC in the modulation of the HIV-specific T-cell response was evaluated. The level of CD3zeta mRNA and ELF-1 protein were analysed by real-time-PCR and western blot, respectively. RESULTS: We found that granulocytic-MDSC (Gr-MDSC) were expanded in HIV+ patients compared with healthy donors; in particular, in cART-treated individuals a higher Gr-MDSC frequency was observed in patients with a CD4 T-cell count below 400 cells/MUl. We found an inverse correlation between the percentage of Gr-MDSC and CD3zeta level. Moreover, in-vitro MDSC depletion induced the up-regulation of CD3zeta in T cells, restoring the functionality of alphabeta, but not gammadelta T cells. The in-vitro effect of isolated MDSC on CD3zeta expression was found cell contact dependent, and was not mediated by previously described molecules. CD3zeta down modulation corresponds to the decrease of its mRNA induced by silencing the transcription factor ELF-1. CONCLUSION: Our data provide new knowledge on mechanisms used by Gr-MDSC in immune-modulation and on their role in the immune reconstitution during antiviral treatments. PMID- 26355673 TI - Incidence and clearance of anal high-risk human papillomavirus in HIV-positive men who have sex with men: estimates and risk factors. AB - BACKGROUND: To estimate incidence and clearance of high-risk human papillomavirus (HR-HPV), and their risk factors, in men who have sex with men (MSM) recently infected by HIV in Spain; 2007-2013. METHODS: Multicenter cohort. HR-HPV infection was determined and genotyped with linear array. Two-state Markov models and Poisson regression were used. RESULTS: We analysed 1570 HR-HPV measurements of 612 MSM over 13 608 person-months (p-m) of follow-up. Median (mean) number of measurements was 2 (2.6), median time interval between measurements was 1.1 years (interquartile range: 0.89-1.4). Incidence ranged from 9.0 [95% confidence interval (CI) 6.8-11.8] per 1000 p-m for HPV59 to 15.9 (11.7-21.8) per 1000 p-m for HPV51. HPV16 and HPV18 had slightly above average incidence: 11.9/1000 p-m and 12.8/1000 p-m. HPV16 showed the lowest clearance for both 'prevalent positive' (15.7/1000 p-m; 95% CI 12.0-20.5) and 'incident positive' infections (22.1/1000 p-m; 95% CI 11.8-41.1). More sexual partners increased HR-HPV incidence, although it was not statistically significant. Age had a strong effect on clearance (P-value < 0.001) due to the elevated rate in MSM under age 25; the effect of HIV-RNA viral load was more gradual, with clearance rate decreasing at higher HIV-RNA viral load (P-value 0.008). CONCLUSION: No large variation in incidence by HR-HPV type was seen. The most common incident types were HPV51, HPV52, HPV31, HPV18 and HPV16. No major variation in clearance by type was observed, with the exception of HPV16 which had the highest persistence and potentially, the strongest oncogenic capacity. Those aged below 25 or with low HIV-RNA- viral load had the highest clearance. PMID- 26355674 TI - Greater change in bone turnover markers for efavirenz/emtricitabine/tenofovir disoproxil fumarate versus dolutegravir + abacavir/lamivudine in antiretroviral therapy-naive adults over 144 weeks. AB - OBJECTIVE: Antiretroviral therapy initiation has been linked to bone mineral density and bone biomarker changes. We assessed long-term bone turnover biomarker effects over 144 weeks in patients initiating dolutegravir (DTG) + abacavir/lamivudine (ABC/3TC) versus efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF). METHODS: Patients randomized in SINGLE received DTG (50 mg once daily) + ABC/3TC or fixed-dose combination EFV/FTC/TDF. We evaluated vitamin D serum levels and bone turnover markers (BTMs), including type 1 collagen cross-linked C-telopeptide (CTx), osteocalcin, bone-specific alkaline phosphatase (BSAP), and procollagen type 1 N-terminal propeptide (P1NP), at baseline and weeks 48, 96, and 144. RESULTS: Among the 833 enrolled patients (68% white, 85% men), baseline median age was 35 years (range 18-85), median CD4 was 338 cells/MUl, and median BMI was 24 kg/m. Fifty-three percent of patients smoked, and 6% reported baseline vitamin D use, with no meaningful differences between groups. Relative to baseline, CTx, osteocalcin, BSAP, and P1NP increased; vitamin D decreased in both groups at weeks 48, 96, and 144. Changes from baseline typically peaked at weeks 48 or 96 and for the four analytes, excluding vitamin D, with the EFV/FTC/TDF group having significantly greater changes from baseline at all time points. CONCLUSION: DTG + ABC/3TC in antiretroviral therapy naive patients resulted in significantly lower increases in BTMs (CTx, osteocalcin, BSAP, P1NP) compared with EFV/FTC/TDF over 144 weeks. The observed changes are consistent with results from other smaller, randomized trials. These differences in BTMs likely correlate with changes in bone mineral density over time. PMID- 26355675 TI - Gut microbiota diversity predicts immune status in HIV-1 infection. AB - OBJECTIVE: HIV-1 infection is characterized by altered intestinal barrier, gut microbiota dysbiosis, and systemic inflammation. We hypothesized that changes of the gut microbiota predict immune dysfunction and HIV-1 progression, and that antiretroviral therapy (ART) partially restores the microbiota composition. DESIGN: An observational study including 28 viremic patients, three elite controllers, and nine uninfected controls. Blood and stool samples were collected at baseline and for 19 individuals at follow-up (median 10 months) during ART. METHODS: Microbiota composition was determined by 16S rRNA sequencing (Illumina MiSeq). Soluble markers of microbial translocation and monocyte activation were analyzed by Limulus Amebocyte Lysate assay or ELISA. RESULTS: Several alpha diversity measures, including number of observed bacterial species and Shannon index, were significantly lower in viremic patients compared to controls. The alpha diversity correlated with CD4 T-cell counts and inversely with markers of microbial translocation and monocyte activation. In multivariate linear regression, for every age and sex-adjusted increase in the number of bacterial species, the CD4 T-cell count increased with 0.88 (95% confidence interval 0.35 1.41) cells/MUl (P = 0.002). After introduction of ART, microbiota alterations persisted with further reduction in alpha diversity. The microbiota composition at the genus level was profoundly altered in viremic patients, both at baseline and after ART, with Prevotella reduced during ART (P < 0.007). CONCLUSIONS: Gut microbiota alterations are closely associated with immune dysfunction in HIV-1 patients, and these changes persist during short-term ART. Our data implicate that re-shaping the microbiota may be an adjuvant therapy in patients commencing successful ART. PMID- 26355676 TI - A Neural Model of Auditory Space Compatible with Human Perception under Simulated Echoic Conditions. AB - In a typical auditory scene, sounds from different sources and reflective surfaces summate in the ears, causing spatial cues to fluctuate. Prevailing hypotheses of how spatial locations may be encoded and represented across auditory neurons generally disregard these fluctuations and must therefore invoke additional mechanisms for detecting and representing them. Here, we consider a different hypothesis in which spatial perception corresponds to an intermediate or sub-maximal firing probability across spatially selective neurons within each hemisphere. The precedence or Haas effect presents an ideal opportunity for examining this hypothesis, since the temporal superposition of an acoustical reflection with sounds arriving directly from a source can cause otherwise stable cues to fluctuate. Our findings suggest that subjects' experiences may simply reflect the spatial cues that momentarily arise under various acoustical conditions and how these cues are represented. We further suggest that auditory objects may acquire "edges" under conditions when interaural time differences are broadly distributed. PMID- 26355677 TI - Short Communication: Investigating a Chain of HIV Transmission Events Due to Homosexual Exposure and Blood Transfusion Based on a Next Generation Sequencing Method. AB - This study investigates a chain of HIV transmission events due to homosexual exposure and blood transfusion in China. The MiSeq platform, a next generation sequencing (NGS) system, was used to obtain genetic details of the HIV-1 env region (336 base pairs). Evolutionary analysis combined with epidemiologic evidence suggests a transmission chain from patient T3 to T2 through homosexual exposure and subsequently to T1 through blood transfusion. More importantly, a phylogenetic study suggested a likely genetic bottleneck for HIV in homosexual transmission from T3 to T2, while T1 inherited the majority of variants from T2. The result from the MiSeq platform is consistent with findings from the epidemiologic survey. The MiSeq platform is a powerful tool for tracing HIV transmissions and intrapersonal evolution. PMID- 26355678 TI - Two nanocage-based metal-organic frameworks with mixed-cluster SBUs and CO2 sorption selectivity. AB - Two nanocage-based metal-organic frameworks respectively built on two and three types of clusters with diisophthalate ligand were constructed, displaying unprecedented (3,4,6)-connected nets, unusual nanocages, and new bipaddle-wheel tetranuclear cluster, as well as highly selective CO2 capture. PMID- 26355679 TI - Efficacy of Supplementation with B Vitamins for Stroke Prevention: A Network Meta Analysis of Randomized Controlled Trials. AB - BACKGROUND: Supplementation with B vitamins for stroke prevention has been evaluated over the years, but which combination of B vitamins is optimal for stroke prevention is unclear. We performed a network meta-analysis to assess the impact of different combinations of B vitamins on risk of stroke. METHODS: A total of 17 trials (86 393 patients) comparing 7 treatment strategies and placebo were included. A network meta-analysis combined all available direct and indirect treatment comparisons to evaluate the efficacy of B vitamin supplementation for all interventions. RESULTS: B vitamin supplementation was associated with reduced risk of stroke and cerebral hemorrhage. The risk of stroke was lower with folic acid plus vitamin B6 as compared with folic acid plus vitamin B12 and was lower with folic acid plus vitamin B6 plus vitamin B12 as compared with placebo or folic acid plus vitamin B12. The treatments ranked in order of efficacy for stroke, from higher to lower, were folic acid plus vitamin B6 > folic acid > folic acid plus vitamin B6 plus vitamin B12 > vitamin B6 plus vitamin B12 > niacin > vitamin B6 > placebo > folic acid plus vitamin B12. CONCLUSIONS: B vitamin supplementation was associated with reduced risk of stroke; different B vitamins and their combined treatments had different efficacy on stroke prevention. Folic acid plus vitamin B6 might be the optimal therapy for stroke prevention. Folic acid and vitamin B6 were both valuable for stroke prevention. The efficacy of vitamin B12 remains to be studied. PMID- 26355681 TI - The Visual N1 Is Sensitive to Deviations from Natural Texture Appearance. AB - Disruptions of natural texture appearance are known to negatively impact performance in texture discrimination tasks, for example, such that contrast negated textures, synthetic textures, and textures depicting abstract art are processed less efficiently than natural textures. Presently, we examined how visual ERP responses (the P1 and the N1 in particular) were affected by violations of natural texture appearance. We presented participants with images depicting either natural textures or synthetic textures made from the original stimuli. Both stimulus types were additionally rendered either in positive or negative contrast. These appearance manipulations (negation and texture synthesis) preserve a range of low-level features, but also disrupt higher-order aspects of texture appearance. We recorded continuous EEG while participants completed a same/different image discrimination task using these images and measured both the P1 and N1 components over occipital recording sites. While the P1 exhibited no sensitivity to either contrast polarity or real/synthetic appearance, the N1 was sensitive to both deviations from natural appearance. Polarity reversal and synthetic appearance affected the N1 latency differently, however, suggesting a differential impact on processing. Our results suggest that stages of visual processing indexed by the P1 and N1 are sensitive to high-order statistical regularities in natural textures and also suggest that distinct violations of natural appearance impact neural responses differently. PMID- 26355680 TI - The Parkinson's Disease-Associated Protein Kinase LRRK2 Modulates Notch Signaling through the Endosomal Pathway. AB - Leucine-rich repeat kinase 2 (LRRK2) is a key molecule in the pathogenesis of familial and idiopathic Parkinson's disease (PD). We have identified two novel LRRK2-associated proteins, a HECT-type ubiquitin ligase, HERC2, and an adaptor like protein with six repeated Neuralized domains, NEURL4. LRRK2 binds to NEURL4 and HERC2 via the LRRK2 Ras of complex proteins (ROC) domain and NEURL4, respectively. HERC2 and NEURL4 link LRRK2 to the cellular vesicle transport pathway and Notch signaling, through which the LRRK2 complex promotes the recycling of the Notch ligand Delta-like 1 (Dll1)/Delta (Dl) through the modulation of endosomal trafficking. This process negatively regulates Notch signaling through cis-inhibition by stabilizing Dll1/Dl, which accelerates neural stem cell differentiation and modulates the function and survival of differentiated dopaminergic neurons. These effects are strengthened by the R1441G ROC domain-mutant of LRRK2. These findings suggest that the alteration of Notch signaling in mature neurons is a component of PD etiology linked to LRRK2. PMID- 26355682 TI - Bayesian inference for duplication-mutation with complementarity network models. AB - We observe an undirected graph G without multiple edges and self-loops, which is to represent a protein-protein interaction (PPI) network. We assume that G evolved under the duplication-mutation with complementarity (DMC) model from a seed graph, G0, and we also observe the binary forest Gamma that represents the duplication history of G. A posterior density for the DMC model parameters is established, and we outline a sampling strategy by which one can perform Bayesian inference; that sampling strategy employs a particle marginal Metropolis-Hastings (PMMH) algorithm. We test our methodology on numerical examples to demonstrate a high accuracy and precision in the inference of the DMC model's mutation and homodimerization parameters. PMID- 26355683 TI - Age Related Macular Degeneration and Total Hip Replacement Due to Osteoarthritis or Fracture: Melbourne Collaborative Cohort Study. AB - Osteoarthritis is the leading cause of total hip replacement, accounting for more than 80% of all total hip replacements. Emerging evidence suggests that osteoarthritis has a chronic inflammatory component to its pathogenesis similar to age-related macular degeneration. We evaluated the association between age related macular degeneration and total hip replacement as proxy for severe osteoarthritis or fractured neck of femur in the Melbourne Collaborative Cohort Study. 20,744 participants had complete data on both age-related macular degeneration assessed from colour fundus photographs taken during 2003-2007 and total hip replacement. Total hip replacements due to hip osteoarthritis and fractured neck of femur during 2001-2011 were identified by linking the cohort records to the Australian Orthopedic Association National Joint Replacement Registry. Logistic regression was used to examine the association between age related macular degeneration and risk of total hip replacement due to osteoarthritis and fracture separately, adjusted for confounders. There were 791 cases of total hip replacement for osteoarthritis and 102 cases of total hip replacement due to fractured neck of femur. After adjustment for age, sex, body mass index, smoking, and grouped country of birth, intermediate age-related macular degeneration was directly associated with total hip replacement for osteoarthritis (odds ratio 1.22, 95% CI 1.00-1.49). Late age-related macular degeneration was directly associated with total hip replacement due to fractured neck of femur (odds ratio 5.21, 95% CI2.25-12.02). The association between intermediate age-related macular degeneration and an increased 10-year incidence of total hip replacement due to osteoarthritis suggests the possibility of similar inflammatory processes underlying both chronic diseases. The association of late age-related macular degeneration with an increased 10-year incidence of total hip replacement due to fractured neck of femur may be due to an increased prevalence of fractures in those with poor central vision associated with the late complications of age-related macular degeneration. PMID- 26355685 TI - Selective Adsorption of Gd(3+) on a Magnetically Retrievable Imprinted Chitosan/Carbon Nanotube Composite with High Capacity. AB - A novel magnetic imprinting nanotechnology for selective capture of Gd(3+) from a mixed solution of rare earth ions was developed by simply adding Gd(3+)-imprinted chitosan/carbon nanotube nanocomposite (IIP-CS/CNT) and silica-coated magnetite nanoparticle (SiO2@Fe3O4). The IIP-CS/CNT was prepared for the first time via a facile "surface deposition-crosslinking" method, exhibiting a well-defined coating structure. Interestingly, the neighboring IIP-CS/CNT monomers were held together as bundles, like a network, containing abundant interstitial spaces. When IIP-CS/CNT and SiO2@Fe3O4 were dispersed in a mixed solution of rare earth ions, the magnetic SiO2@Fe3O4 submicrospheres would be trapped in or adhere to the IIP-CS/CNT network, leading to the magnetization of IIP-CS/CNT; meanwhile, Gd(3+) ions could be selectively captured by the magnetized IIP-CS/CNT. Saturation adsorption capacity for Gd(3+) was up to 88 mg g(-1) at 303.15 K, which is significantly higher than the Gd(3+) adsorption capacities for the reported rare earth ion-imprinted adsorbents over recent years. The selectivity coefficients relative to La(3+) and Ce(3+) were 3.50 and 2.23, respectively, which are very similar to those found for other reported CS-based imprinted materials. Moreover, the imprinted adsorbents could be easily and rapidly retrieved by an external magnetic field without the need of additional centrifugation or filtration, greatly facilitating the separation process. Test of reusability demonstrated that the magnetized IIP-CS/CNT could be repeatedly used without any significant loss in binding capacity. Overall, this work not only provides new insights into the fabrication of magnetic imprinted CS-based composite, but also highlights its application for selective adsorption toward rare earth ions. PMID- 26355684 TI - Matrix Metalloproteinase-2 (MMP-2) Gene Deletion Enhances MMP-9 Activity, Impairs PARP-1 Degradation, and Exacerbates Hepatic Ischemia and Reperfusion Injury in Mice. AB - Hepatic ischemia and reperfusion injury (IRI) is an inflammatory condition and a significant cause of morbidity and mortality after surgery. Matrix metalloproteinases (MMPs) have been widely implicated in the pathogenesis of inflammatory diseases. Among the different MMPs, gelatinases (MMP-2 and MMP-9) are within the most prominent MMPs detected during liver IRI. While the role of MMP-9 in liver damage has been fairly documented, direct evidence of the role for MMP-2 activity in hepatic IRI remains to be established. Due to the lack of suitable inhibitors to target individual MMPs in vivo, gene manipulation is as an essential tool to assess MMP direct contribution to liver injury. Hence, we used MMP-2-/- deficient mice and MMP-2+/+ wild-type littermates to examine the function of MMP-2 activity in hepatic IRI. MMP-2 expression was detected along the sinusoids of wild-type livers before and after surgery and in a small population of leukocytes post-IRI. Compared to MMP-2+/+ mice, MMP-2 null (MMP-2-/ ) mice showed exacerbated liver damage at 6, 24, and 48 hours post-reperfusion, which was fatal in some cases. MMP-2 deficiency resulted in upregulation of MMP-9 activity, spontaneous leukocyte infiltration in naive livers, and amplified MMP-9 dependent transmigration of leukocytes in vitro and after hepatic IRI. Moreover, complete loss of MMP-2 activity impaired the degradation of poly (ADP-ribose) polymerase (PARP-1) in extensively damaged livers post-reperfusion. However, the administration of a PARP-1 inhibitor to MMP-2 null mice restored liver preservation to almost comparable levels of MMP-2+/+ mice post-IRI. Deficient PARP-1 degradation in MMP-2-null sinusoidal endothelial cells correlated with their increased cytotoxicity, evaluated by the measurement of LDH efflux in the medium. In conclusion, our results show for the first time that MMP-2 gene deletion exacerbates liver IRI. Moreover, they offer new insights into the MMP-2 modulation of inflammatory responses, which could be relevant for the design of new pharmacological MMP-targeted agents to treat hepatic IRI. PMID- 26355687 TI - Cyclic Phosphine Oxides and Phosphinamides from Di-Grignard Reagents and Phosphonic Dichlorides: Modular Access to Annulated Phospholanes. AB - The reaction between 1,4-di-Grignard reagents and phosphonous(III) dichlorides is a classical method for the direct synthesis of phospholanes. Reported here is an extension of this approach to the preparation of value-added, annulated phospholane oxides, achieved through the combination of carbocyclic-fused di Grignard reagents and readily available phosphonic(V) dichlorides. The procedure is amenable to (benz)annulation at both the 2,3- and 3,4-positions of the phospholane ring, and a variety of aliphatic, cyclic and aryl P-electrophiles are tolerated in reasonable to excellent yields. PMID- 26355686 TI - A National Study on Nurses' Exposure to Occupational Violence in Lebanon: Prevalence, Consequences and Associated Factors. AB - BACKGROUND: Healthcare institutions have commonly reported exposure of employees, particularly nurses, to high levels of occupational violence. Despite such evidence in the Middle East Region, there is a dearth of national studies that have systematically investigated this phenomenon. This study investigates the prevalence, characteristics, consequences and factors associated with nurses' exposure to occupational violence in Lebanon. METHODS: A cross-sectional design was utilized to survey a nationally representative sample of 915 nurses registered with the Order of Nurses in Lebanon. Stratified random sampling by governorate was utilized. Individually-mailed questionnaires collected information on exposure to violence, degree of burnout and demographic/professional background. The main outcome variables were exposure to verbal abuse (never, 1-3, 4-9 and 10+ times) and physical violence (never, ever) over the past 12-months. Descriptive statistics were used to estimate prevalence of violence. Multivariable, binomial and multinomial regression models were carried out to investigate the correlates of exposure to verbal abuse and physical violence, respectively. RESULTS: Response rate was 64.8%. Over the last year, prevalence of nurses' exposure to verbal abuse was 62%, (CI: 58-65%) and physical violence was 10%, (CI: 8-13%). Among respondents, 31.7% of nurses indicated likelihood to quit their jobs and 22.3% were undetermined. Furthermore, 54.1% reported high levels of emotional exhaustion and 28.8% reported high levels of depersonalization. Compared to nurses with no exposure to verbal abuse, nurses reporting high exposure had high levels of emotional exhaustion (OR:6.4; CI:1.76 23.32), depersonalization (OR:6.8; CI: 3-15) and intention to quit job (OR:3.9; CI: 1.8-8.3). They further reported absence of anti-violence policies at their institutions (OR: 3; CI: 1.5-6.3). Nurses that were ever exposed to physical violence were more likely to be males (OR: 2.2; CI: 1.1-4.3), working day and night shifts (OR: 2.8; CI: 1.4-5.5) and subject to ten or more incidents of verbal abuse per year (OR: 46.7; CI: 10.1-214). CONCLUSIONS: An alarming two thirds of respondents reported exposure to verbal abuse which was found to be a significant predictor of the three subscales of burnout, intention to quit and exposure to physical violence. The prevalence of exposure to physical violence is disconcerting due to its severe consequences. Policy and decision-makers are urged to use study findings for policy and practice interventions to create safe work environments conducive to nurses' productivity and retention. PMID- 26355688 TI - NiCo2S4 nanowires array as an efficient bifunctional electrocatalyst for full water splitting with superior activity. AB - The present communication reports the topotactic conversion of NiCo2O4 nanowires array on carbon cloth (NiCo2O4 NA/CC) into NiCo2S4 NA/CC, which is used as an efficient bifunctional electrocatalyst for water splitting with good durability and superior activity in 1.0 M KOH. This NiCo2S4 NA/CC electrode produces 100 mA cm(-2) at an overpotential of 305 mV for hydrogen evolution and 100 mA cm(-2) at an overpotential of 340 mV for oxygen evolution. To afford a 10 mA cm(-2) water splitting current, the alkaline water electrolyzer made from NiCo2S4 NA/CC needs a cell voltage of 1.68 V, which is 300 mV less than that for NiCo2O4 NA/CC, and has good stability. PMID- 26355689 TI - Concurrent Minimally Invasive Aortic Valve Replacement and Coronary Artery Bypass via Limited Right Anterior Thoracotomy. AB - An 89-year-old man and an 80-year-old woman were treated surgically for critical aortic stenosis secondary to senile calcific aortic disease and high-grade calcified lesions in the ostium of the right coronary artery. Minimally invasive aortic valve replacement and concurrent coronary artery bypass grafting were performed concurrently through a 5-cm right anterior thoracotomy in the second intercostal space. Surgery was uncomplicated in both cases, with no adverse events. Both patients were alive and well at midterm follow-up. Concurrent minimally invasive aortic valve replacement and coronary artery bypass grafting can be performed successfully through a limited right anterior thoracotomy. PMID- 26355690 TI - Minimally Invasive Transaortic Mitral Decalcification During Aortic Valve Replacement. AB - Mitral annular calcification accompanied by aortic stenosis is hazardous for both double-valve replacement and transcatheter aortic valve implantation. Less invasive mitral procedure is required in this condition, and minimally invasive approach may further reduce the operative risk in high-risk patients. Here, we report minimally invasive transaortic mitral decalcification during aortic valve replacement through minithoracotomy. We believe that this option is feasible in patients who are at prohibitive risk for double-valve replacement or transcatheter aortic valve implantation because of severe mitral annular calcification. PMID- 26355691 TI - Endoscopic Resection of a Giant Left Atrial Appendage. AB - A 23-year-old woman with a history of arterial hypertension presented to our institution complaining of dyspnea and chest pain. Her workup including echocardiography and magnetic resonance imaging revealed an aneurysm of the left atrial appendage. No thrombus was identified in the aneurysm or left atrial appendage, and the patient was in sinus rhythm. She was started on prophylactic anticoagulation, and surgical resection of the aneurysm was recommended as a definitive treatment of this lesion. The surgery was performed using a minimally invasive left-sided thoracoscopy approach. The entire left atrial appendage including the aneurysm was removed at its base using an articulating endoscopic stapler device. On postoperative echocardiography, no residual left atrial appendage tissue was evident. The patient could be taken off oral anticoagulation and left the hospital in good condition. PMID- 26355692 TI - In-Graft Endovascular Stenting Repair for Supravalvular Stenosis From Aortic Rupture After Balloon-Expanding Transcatheter Aortic Valve Implantation. AB - An 81-year-old man with high-grade aortic valve stenosis and status post-coronary artery bypass grafting and supracoronary replacement of the ascending aorta was referred for transcatheter aortic valve implantation. He was in New York Heart Association class III and had dyspnea. After appropriate screening, we implanted a 29-mm SAPIEN XT valve (Edwards Lifesciences, Irvine, CA USA) through a transapical approach because of severe peripheral arterial occlusive disease. Postinterventional aortography revealed correct positioning and function of the valve and free coronary ostia but contrast extravasation in the vicinity of the interposed vascular prosthesis, resulting in severe luminal narrowing. We chose to manage the stenosis with an endovascular stent. After stenting, extravascular compression was markedly reduced, and the pressure gradient disappeared. The patient was discharged home on the 20th postoperative day. Three months later, computed tomography depicted correct positioning of both grafts. The patient's general health is good, and he is now in New York Heart Association class II. This case illustrates a complication of transcatheter aortic valve implantation specific for patients with an ascending aortic graft. Although stenting may be a good solution, as depicted by this case, self-expanding transcatheter aortic valves should be preferred in patients with ascending aortic grafts to avoid the described complication. PMID- 26355693 TI - A carbon dot-based fluorescence turn-on sensor for hydrogen peroxide with a photo induced electron transfer mechanism. AB - A carbon dot-based fluorescence turn-on sensor for hydrogen peroxide (H2O2) with a photo-induced electron transfer mechanism was developed. The sensor exhibits good selectivity, sensitivity, and rapid response to H2O2 with a detection limit of 84 nM. The sensor maintains excellent sensing performance over a wide pH range. PMID- 26355694 TI - The Effect of Quantitative Computed Tomography Acquisition Protocols on Bone Mineral Density Estimation. AB - Osteoporosis is characterized by bony material loss and decreased bone strength leading to a significant increase in fracture risk. Patient-specific quantitative computed tomography (QCT) finite element (FE) models may be used to predict fracture under physiological loading. Material properties for the FE models used to predict fracture are obtained by converting grayscale values from the CT into volumetric bone mineral density (vBMD) using calibration phantoms. If there are any variations arising from the CT acquisition protocol, vBMD estimation and material property assignment could be affected, thus, affecting fracture risk prediction. We hypothesized that material property assignments may be dependent on scanning and postprocessing settings including voltage, current, and reconstruction kernel, thus potentially having an effect in fracture risk prediction. A rabbit femur and a standard calibration phantom were imaged by QCT using different protocols. Cortical and cancellous regions were segmented, their average Hounsfield unit (HU) values obtained and converted to vBMD. Estimated vBMD for the cortical and cancellous regions were affected by voltage and kernel but not by current. Our study demonstrated that there exists a significant variation in the estimated vBMD values obtained with different scanning acquisitions. In addition, the large noise differences observed utilizing different scanning parameters could have an important negative effect on small subregions containing fewer voxels. PMID- 26355695 TI - Two-speed phacoemulsification for soft cataracts using optimized parameters and procedure step toolbar with the CENTURION Vision System and Balanced Tip. AB - PURPOSE: To present a cause of posterior capsule aspiration and a technique using optimized parameters to prevent it from happening when operating soft cataracts. PATIENTS AND METHODS: A prospective list of posterior capsule aspiration cases was kept over 4,062 consecutive cases operated with the Alcon CENTURION machine and Balanced Tip. Video analysis of one case of posterior capsule aspiration was accomplished. A surgical technique was developed using empirically derived machine parameters and customized setting-selection procedure step toolbar to reduce the pace of aspiration of soft nuclear quadrants in order to prevent capsule aspiration. RESULTS: Two cases out of 3,238 experienced posterior capsule aspiration before use of the soft quadrant technique. Video analysis showed an attractive vortex effect with capsule aspiration occurring in 1/5 of a second. A soft quadrant removal setting was empirically derived which had a slower pace and seemed more controlled with no capsule aspiration occurring in the subsequent 824 cases. The setting featured simultaneous linear control from zero to preset maximums for: aspiration flow, 20 mL/min; and vacuum, 400 mmHg, with the addition of torsional tip amplitude up to 20% after the fluidic maximums were achieved. A new setting selection procedure step toolbar was created to increase intraoperative flexibility by providing instantaneous shifting between the soft and normal settings. CONCLUSION: A technique incorporating a reduced pace for soft quadrant acquisition and aspiration can be accomplished through the use of a dedicated setting of integrated machine parameters. Toolbar placement of the procedure button next to the normal setting procedure button provides the opportunity to instantaneously alternate between the two settings. Simultaneous surgeon control over vacuum, aspiration flow, and torsional tip motion may make removal of soft nuclear quadrants more efficient and safer. PMID- 26355696 TI - CD44 sensitivity of platelet activation, membrane scrambling and adhesion under high arterial shear rates. AB - CD44 is required for signalling of macrophage migration inhibitory factor (MIF), an anti-apoptotic pro-inflammatory cytokine. MIF is expressed and released from blood platelets, key players in the orchestration of occlusive vascular disease. Nothing is known about a role of CD44 in the regulation of platelet function. The present study thus explored whether CD44 modifies degranulation (P-selectin exposure), integrin activation, caspase activity, phosphatidylserine exposure on the platelet surface, platelet volume, Orai1 protein abundance and cytosolic Ca(2+)-activity ([Ca2+]i). Platelets from mice lacking CD44 (cd44(-/-)) were compared to platelets from corresponding wild-type mice (cd44(+/+)). In resting platelets, P-selectin abundance, alpha(IIb)beta3 integrin activation, caspase-3 activity and phosphatidylserine exposure were negligible in both genotypes and Orai1 protein abundance, [Ca2+]i, and volume were similar in cd44(-/-) and cd44(+/+) platelets. Platelet degranulation and alpha(IIb)beta3 integrin activation were significantly increased by thrombin (0.02 U/ml), collagen related peptide (CRP, 2 ug/ml and Ca(2+)-store depletion with thapsigargin (1 uM), effects more pronounced in cd44(-/-) than in cd44(+/+) platelets. Thrombin (0.02 U/ml) increased platelet [Ca2+]i, caspase-3 activity, phosphatidylserine exposure and Orai1 surface abundance, effects again significantly stronger in cd44(-/-) than in cd44(+/+) platelets. Thrombin further decreased forward scatter in cd44( /-) and cd44(+/+) platelets, an effect which tended to be again more pronounced in cd44(-/-) than in cd44(+/+) platelets. Platelet adhesion and in vitro thrombus formation under high arterial shear rates (1,700 s(-1)) were significantly augmented in cd44(-/-) mice. In conclusion, genetic deficiency of CD44 augments activation, apoptosis and pro-thrombotic potential of platelets. PMID- 26355697 TI - Confidence intervals for the ratio of two median residual lifetimes with left truncated and right-censored data. AB - The confidence intervals for the ratio of two median residual lifetimes are developed for left-truncated and right-censored data. The approach of Su and Wei (1993) is first extended by replacing the Kaplan-Meier survival estimator with the estimator of the conditional survival function (Lynden-Bell, 1971). This procedure does not involve a nonparametric estimation of the probability density function of the failure time. However, the Su and Wei type confidence intervals are very conservative even for larger sample size. Therefore, this article proposes an alternative confidence interval for the ratio of two median residual lifetimes, which is not only without nonparametric estimation of the density function of failure times but is also computationally simpler than the Su and Wei type confidence interval. A simulation study is conducted to examine the accuracy of these confidence intervals and the implementation of these confidence intervals to two real data sets is illustrated. PMID- 26355698 TI - Update on Hepatitis C Virus and HIV Coinfection. AB - Chronic hepatitis C virus (HCV) infection has historically been difficult to treat in the HIV-infected population, owing to generally poor responses to interferon-based therapies. The recent rapid development of directly acting antiviral agents (DAAs) against HCV has the potential to revolutionize treatment of this infection in the HIV population by improving tolerability and outcome, and, ultimately, reducing the significant burden of liver-related morbidity and mortality in this population. Clinical trials to address the safety and efficacy of novel DAAs in the HCV/HIV coinfected population are ongoing, and show much promise. The rapidity of current drug discovery in the field of HCV is both impressive and daunting for clinicians who will have to master these drugs. Going forward, the inclusion of individuals from this large and growing patient population in clinical trials will be of paramount importance. PMID- 26355699 TI - Scalp Lesion in a Man With Chronic Sun Exposure. PMID- 26355700 TI - Development of Novel Bioluminescent Sensor to Detect and Discriminate between Vitamin D Receptor Agonists and Antagonists in Living Cells. AB - Active forms of vitamin D regulate the expression of multiple genes that play essential roles in calcium and phosphate homeostasis, cell differentiation, and the immune system via the vitamin D receptor (VDR). Many vitamin D analogs have been synthesized for clinical use in the treatment of type I rickets, osteoporosis, renal osteodystrophy, psoriasis, leukemia, and breast cancer. We have constructed two fusion proteins containing split-luciferase and the ligand binding domain (LBD) of the VDR designated as LucN-LBD-LucC and LucC-LBD-LucN. Remarkably, the LucC-LBD-LucN, which has the C-terminal domain of luciferase at the N-terminus of the fusion protein, was a significantly better biosensor than LucN-LBD-LucC. Addition of the VDR agonists to COS-7 cells expressing LucC-LBD LucN dramatically reduced luciferase activity. In contrast, the VDR antagonist significantly increased the chimeric luciferase activity in a dose- and time dependent manner. Our results on chimeric luciferases containing the LBDs of mutant VDRs derived from patients with vitamin D-dependent type II rickets indicated that our system could detect a conformational change of the LBD of the VDR likely based on a positional change of the helix 12, which occurs upon ligand binding. This novel system to detect and discriminate between VDR agonists and antagonists could be useful for the screening and identification of chemical compounds that bind to normal or mutant VDRs with high affinity. PMID- 26355701 TI - Carcinogenic activity of PbS quantum dots screened using exosomal biomarkers secreted from HEK293 cells. AB - Lead sulfide (PbS) quantum dots (QDs) have been applied in the biomedical area because they offer an excellent platform for theragnostic applications. In order to comprehensively evaluate the biocompatibility of PbS QDs in human cells, we analyzed the exosomes secreted from cells because exosomes are released during cellular stress to convey signals to other cells and serve as a reservoir of enriched biomarkers. PbS QDs were synthesized and coated with 3-mercaptopropionic acid (MPA) to allow the particles to disperse in water. Exosomes were isolated from HEK293 cells treated with PbS-MPA at concentrations of 0 ug/mL, 5 ug/mL, and 50 ug/mL, and the exosomal expression levels of miRNAs and proteins were analyzed. As a result, five miRNAs and two proteins were proposed as specific exosomal biomarkers for the exposure of HEK293 cells to PbS-MPA. Based on the pathway analysis, the molecular signature of the exosomes suggested that PbS-MPA QDs had carcinogenic activity. The comet assay and expression of molecular markers, such as p53, interleukin (IL)-8, and C-X-C motif chemokine 5, indicated that DNA damage occurred in HEK293 cells following PbS-MPA exposure, which supported the carcinogenic activity of the particles. In addition, there was obvious intensification of miRNA expression signals in the exosomes compared with that of the parent cells, which suggested that exosomal biomarkers could be detected more sensitively than those of whole cellular extracts. PMID- 26355702 TI - Determinants of Heart Failure Self-Care Maintenance and Management in Patients and Caregivers: A Dyadic Analysis. AB - Disease self-management is a critical component of maintaining clinical stability for patients with chronic illness. This is particularly evident in the context of heart failure (HF), which is the leading cause of hospitalization for older adults. HF self-management, commonly known as HF self-care, is often performed with the support of informal caregivers. However, little is known about how a HF dyad manages the patient's care together. The purpose of this study was to identify determinants of patient and caregiver contributions to HF self-care maintenance (daily adherence and symptom monitoring) and management (appropriate recognition and response to symptoms), utilizing an approach that controls for dyadic interdependence. This was a secondary analysis of cross-sectional data from 364 dyads of Italian HF patients and caregivers. Multilevel modeling was used to identify determinants of HF self-care within patient-caregiver dyads. Patients averaged 76.2 (SD = 10.7) years old, and a slight majority (56.9%) was male, whereas caregivers averaged 57.4 (SD = 14.6) years old, and about half (48.1%) were male. Most caregivers were adult children (48.4%) or spouses (32.7%) of patients. Both patients and caregivers reported low levels of HF maintenance and management behaviors. Significant individual and dyadic determinants of self care maintenance and self-care management included gender, quality of life, comorbid burden, impaired ADLs, cognition, hospitalizations, HF duration, relationship type, relationship quality, and social support. These comprehensive dyadic models assist in elucidating the complex nature of patient-caregiver relationships and their influence on HF self-care, leading to more effective ways to intervene and optimize outcomes. PMID- 26355703 TI - Modeling the positioning of single needle electrodes for the treatment of breast cancer in a clinical case. AB - BACKGROUND: Breast cancer is the most common cancer in women worldwide and is the second most common cause of cancer death in women. Electrochemotherapy (ECT) used in early-phase clinical trials for the treatment of primary breast cancer resulted in a not complete tumor necrosis in most cases. The present study was undertaken to analyze the feasibility to use ECT to treat patients with histologically proven unifocal ductal breast cancer. In particular, results of ECT treatment in a clinical case are compared with the ones of a simplified 3D dosimetric model. METHODS: This clinical study was conducted with the pulse generator Cliniporator Vitae (IGEA, Carpi, Italy). ECT procedures were performed according to ESOPE standard operating procedures. Five single needle electrodes were used with one positioned in the center of the tumor, and the other four distributed around the nodule. Histological images of the resected tumor are compared with the maps of the electric field obtained with a simplified 3D model in Comsol Multiphysics v 4.3. RESULTS: The results of the clinical case demonstrated a reduced efficacy of the ECT treatment described. The proposed simple numerical model of the breast tumor located in a low conductive tissue suggests that this is due to the reduced electric field induced inside the tumor with such 5 electrodes placement. However, where the electric field is predicted higher than the reversible electroporation threshold (E>400 V/cm), also the histological images confirm the necrosis of the target with a good agreement between the modeled and clinical results. CONCLUSIONS: The results suggest the dependence of the effectiveness of the treatment on the careful placement of the electrodes. A detailed planned procedure for the tumor analysis after the treatment is also needed in order to better correlate the single electrode positions and the histological images. Simulation models could be used to identify better electrodes configuration in planning the experimental protocol for ECT treatment of breast tumors. PMID- 26355704 TI - Naturally occurring hepatitis C virus protease inhibitors resistance-associated mutations among chronic hepatitis C genotype 1b patients with or without HIV co infection. AB - The aim of this study was to measure the frequency of natural mutations in hepatitis C virus (HCV) mono-infected and HIV/HCV co-infected protease inhibitor (PI)-naive patients. METHODS: Population sequence of the non-structural (NS)3 protease gene was evaluated in 90 HCV mono-infected and 96 HIV/HCV co-infected PI treatment-naive patients. The natural prevalence of PI resistance mutations in both groups was compared. RESULTS: Complete HCV genotype 1b NS3 sequence information was obtained for 152 (81.72%) samples. Seven sequences (8.33%) of the 84 HCV mono-infected patients and 21 sequences (30.88%) of the 68 HIV/HCV co infected patients showed amino acid substitutions associated with HCV PI resistance. There was a significant difference in the natural prevalence of PI resistance mutations between these two groups (P = 0.000). The mutations T54S, R117H and N174F were observed in 1.19%, 5.95% and 1.19% of HCV mono-infected patients. The mutations F43S, T54S, Q80K/R, R155K, A156G/V, D168A/E/G and V170A were found in 1.47%, 4.41%, 1.47%/1.47%, 2.94%, 23.53%/1.47%, 1.47%/1.47%/1.47% and 1.47% of HIV/HCV co-infected patients, respectively. In addition, the combination mutations in the NS3 region were detected only in HIV/HCV genotype 1b co-infected patients. CONCLUSION: Naturally occurring HCV PI resistance mutations existed in HCV mono-infected and HIV/HCV co-infected genotype 1b PI-naive patients. HIV co-infection was associated with a greater frequency of PI resistance mutations. The impact of HIV infection on baseline HCV PI resistance mutations and treatment outcome in chronic hepatitis C (CHC) patients should be further analyzed. PMID- 26355705 TI - Comparative Mapping of GABA-Immunoreactive Neurons in the Buccal Ganglia of Nudipleura Molluscs. AB - Phylogenetic comparisons of neurotransmitter distribution are important for understanding the ground plan organization of nervous systems. This study describes the gamma-aminobutyric acid (GABA)-immunoreactive (GABA-ir) neurons in the buccal ganglia of six sea slug species (Mollusca, Gastropoda, Euthyneura, Nudipleura). In the nudibranch species, Hermissenda crassicornis, Tritonia diomedea, Tochuina tetraquetra, and Dendronotus iris, the number of GABA-ir neurons was highly consistent. Another nudibranch, Melibe leonina, however, contained approximately half the number of GABA-ir neurons. This may relate to its loss of a radula and its unique feeding behavior. The GABA immunoreactivity in a sister group to the nudibranchs, Pleurobranchaea californica, differed drastically from that of the nudibranchs. Not only did it have significantly more GABA-ir neurons but it also had a unique GABA distribution pattern. Furthermore, unlike the nudibranchs, the Pleurobranchaea GABA distribution was also different from that of other, more distantly related, euopisthobranch and panpulmonate snails and slugs. This suggests that the Pleurobranchaea GABA distribution may be a derived feature, unique to this lineage. The majority of GABA-ir axons and neuropil in the Nudipleura were restricted to the buccal ganglia, commissures, and connectives. However, in Tritonia and Pleurobranchaea, we detected a few GABA ir fibers in buccal nerves that innervate feeding muscles. Although the specific functions of the GABA-ir neurons in the species in this study are not known, the innervation pattern suggests these neurons may play an integrative or regulatory role in bilaterally coordinated behaviors in the Nudipleura. PMID- 26355707 TI - Influence of Pastoralists' Sociocultural Activities on Tsetse-Trypanosome-Cattle Reservoir Interface: The Risk of Human African Trypanosomiasis in North-Central Nigeria. AB - The study investigated socio-cultural characteristics of pastoralists that influenced on the tsetse-trypanosome-cattle reservoir interface thereby predisposing them to HAT in Niger State, North-central Nigeria. It was a cross sectional survey of adult pastoral herders, aged 30 years and above, and conducted between October 2012 and February 2013. A face-to-face structured questionnaire was administered on the pastoralists nested in 96 cattle herds with questions focused on pastoralists' socio-cultural activities and behavioral practices related to HAT risk. Descriptive and analytic statistics were used to describe the obtained data. A total of 384 pastoralists participated, with mean age of 49.6 A +/- 10.76 SD years. Male respondents constituted 86.7% of gender, while pastoralists of age group 40-49 years constituted 35.4% of respondents. About 59.4% of the pastoralists had knowledge about HAT and its symptoms and only 33.9% of them believed that cattle served as reservoir of HAT trypanosome. Knowledge/belief levels of the pastoralists about African trypanosomiasis occurrence in humans and animals were statistically significant. Males were four times more likely to be exposed to HAT (OR = 3.67; 95% CI: 1.42, 9.52); age group 60-69 was also four times more likely to be exposed (OR = 3.59; 95% CI: 1.56, 8.28); and nomadic pastoralists were two times more likely to be exposed to HAT (OR = 2.07; 95% CI: 1.37, 3.14). All cultural practices significantly influenced exposure to HAT with extensive husbandry system three times more likely to predisposed pastoralists to HAT (OR = 3.21; 95% CI: 1.65, 6.24). Socio-cultural characteristics of pastoralists influenced exposure to HAT risk and, therefore, there is a need to sensitize them to bring changes to their socio-cultural practices and perceptions to achieve effective and long term sustainable HAT control. Elimination strategies of parasites in animals and vectors should be considered to avoid reintroduction from animal reservoirs. PMID- 26355706 TI - Association between levels of pentraxin 3 and incidence of chronic kidney disease in the elderly. AB - OBJECTIVE: Higher levels of the novel inflammatory marker pentraxin 3 (PTX3) predict cardiovascular mortality in patients with chronic kidney disease (CKD). Yet, whether PTX3 predicts worsening of kidney function has been less well studied. We therefore investigated the associations between PTX3 levels, kidney disease measures and CKD incidence. METHODS: Cross-sectional associations between serum PTX3 levels, urinary albumin/creatinine ratio (ACR) and cystatin C estimated glomerular filtration rate (GFR) were assessed in two independent community-based cohorts of elderly subjects: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS, n = 768, 51% women, mean age 75 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 651, mean age 77 years). The longitudinal association between PTX3 level at baseline and incident CKD (GFR <60 mL(-1) min(-1) 1.73 m(-2) was also analysed (number of events/number at risk: PIVUS 229/746, ULSAM 206/315). RESULTS: PTX3 levels were inversely associated with GFR [PIVUS: B-coefficient per 1 SD increase -0.16, 95% confidence interval (CI) -0.23 to -0.10, P < 0.001; ULSAM: B-coefficient per 1 SD increase -0.09, 95% CI -0.16 to -0.01, P < 0.05], but not ACR, after adjusting for age, gender, C reactive protein and prevalent cardiovascular disease in cross-sectional analyses. In longitudinal analyses, PTX3 levels predicted incident CKD after 5 years in both cohorts [PIVUS: multivariable odds ratio (OR) 1.21, 95% CI 1.01 1.45, P < 0.05; ULSAM: multivariable OR 1.37, 95% CI 1.07-1.77, P < 0.05]. CONCLUSIONS: Higher PTX3 levels are associated with lower GFR and independently predict incident CKD in elderly men and women. Our data confirm and extend previous evidence suggesting that inflammatory processes are activated in the early stages of CKD and drive impairment of kidney function. Circulating PTX3 appears to be a promising biomarker of kidney disease. PMID- 26355709 TI - Surface modification by plasma etching impairs early vascularization and tissue incorporation of porous polyethylene (Medpor(r) ) implants. AB - Porous polyethylene (Medpor(r)) is commonly used in craniofacial reconstructive surgery. Rapid vascularization and tissue incorporation are crucial for the prevention of migration, extrusion, and infection of the biomaterial. Therefore, we analyzed whether surface modification by plasma etching may improve the early tissue response to Medpor(r). Medpor(r) samples were treated in a plasma chamber at low (20 W; LE-PE) and high energy levels (40 W; HE-PE). The samples and non treated controls were implanted into mouse dorsal skinfold chambers to analyze angiogenesis, inflammation, and granulation tissue formation over 14 days using intravital fluorescence microscopy, histology, and immunohistochemistry. Scanning electron microscopy (SEM) analyses revealed that elevating energy levels of plasma etching progressively increase the oxygen surface content and surface roughness of Medpor(r). This did not affect the leukocytic response to the implants. However, LE-PE and HE-PE samples exhibited an impaired vascularization. This was associated with a reduced formation of a collagen-rich granulation tissue at the implantation site. Additional in vitro experiments showed a reduced cell attachment on plasma-etched Medpor(r). Thus, plasma etching may not be recommended to improve the clinical outcome of reconstructive interventions using Medpor(r). However, it may be beneficial for temporarily implanted polyethylene based biomedical devices for which tissue incorporation is undesirable. (c) 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1738 1748, 2016. PMID- 26355708 TI - Frequency of del(12p) is commonly underestimated in myelodysplastic syndromes: Results from a German diagnostic study in comparison with an international control group. AB - In myelodysplastic syndromes (MDS), deletion of the short arm of chromosome 12 (del(12p)) is usually a small abnormality, rarely detected as a single aberration by chromosome banding analysis (CBA) of bone marrow metaphases. Del(12p) has been described in 0.6 to 5% of MDS patients at initial diagnosis and is associated with a good to intermediate prognosis as a sole anomaly according to current scoring systems. Here, we present the results of a systematic del(12p) testing in a German prospective diagnostic study (clinicaltrials.gov: NCT01355913) on 367 MDS patients in whom CD34+ peripheral blood cells were analysed for the presence of del(12p) by sequential fluorescence in situ hybridization (FISH) analyses. A cohort of 2,902 previously published MDS patients diagnosed by CBA served as control. We demonstrate that, using a sensitive FISH technique, 12p deletion occurs significantly more frequently in MDS than previously described (7.6% by CD34+ PB-FISH vs. 1.6% by CBA, P < 0.001) and is often associated with other aberrations (93% by CD34+ PB-FISH vs. 60% by CBA). Additionally, the detection rate can be increased by repeated analyses in a patient over time which is important for the patient's prognosis to distinguish a sole anomaly from double or complex aberrations. To our knowledge, this is the first study to screen for 12p deletions with a suitable probe for ETV6/TEL in 12p13. Our data suggest that the supplement of a probe for the detection of a 12p deletion to common FISH probe panels helps to avoid missing a del(12p), especially as part of more complex aberrations. PMID- 26355710 TI - Diverse expression patterns of the EMT suppressor grainyhead-like 2 (GRHL2) in normal and tumour tissues. AB - The transcription factor grainyhead-like 2 (GRHL2) plays a crucial role in various developmental processes. Although GRHL2 recently has attracted considerable interest in that it could be identified as a novel suppressor of the epithelial-to-mesenchymal transition, evidence is emerging that GRHL2 also exhibits tumour-promoting activities. Aim of the present study therefore was to help defining the relevance of GRHL2 for human cancers by performing a comprehensive immunohistochemical analysis of GRHL2 expression in normal (n = 608) and (n = 3,143) tumour tissues using tissue microarrays. Consistent with its accepted role in epithelial morphogenesis, GRHL2 expression preferentially but not exclusively was observed in epithelial cells. Regenerative and proliferating epithelial cells with stem cell features showed a strong GRHL2 expression. Highly complex GRHL2 expression patterns indicative of both reduced and elevated GRHL2 expression in tumours, possibly reflecting potential tumour-suppressing as well as oncogenic functions of GRHL2 in distinct human tumours, were observed. A dysregulation of GRHL2 expression for the first time was found in tumours of non epithelial origin (e.g., astrocytomas, melanomas). We also report GRHL2 copy number gains which, however, did not necessarily translate into increased GRHL2 expression levels in cancer cells. Results obtained by meta-analysis of gene expression microarray data in conjunction with functional assays demonstrating a direct regulation of HER3 expression further point to a potential therapeutic relevance of GRHL2 in ovarian cancer. Hopefully, the results presented in this study may pave the way for a better understanding of the yet largely unknown function of GRHL2 in the initiation, progression and also therapy of cancers. PMID- 26355711 TI - Two decades of risk factors and transfusion-transmissible infections in Dutch blood donors. AB - BACKGROUND: Risk behavior-based donor selection procedures are widely used to mitigate the risk of transfusion-transmissible infections (TTIs), but their effectiveness is disputed in countries with low residual risks of TTIs. STUDY DESIGN AND METHODS: In 1995 to 2014, Dutch blood donors infected with hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), human T lymphotropic virus (HTLV), or syphilis were interviewed by trained medical counselors to identify risk factors associated with TTIs. Trends in the prevalence and incidence of TTIs were analyzed using binomial regression models. RESULTS: A total of 972 new donors and 381 repeat donors had TTIs. New donors had higher rates of TTIs compared to repeat donors. Although the HBV and HCV prevalence gradually decreased over time, the incidence of all five TTIs remained stable during the past two decades. In new donors the TTIs had the following risk profiles: "blood-blood contact" for HCV, "unprotected sex" for HIV and syphilis, and "country of birth" for HBV and HTLV. In infected repeat donors, sexual risk factors predominated for all TTIs. At posttest counseling, 28% of infected repeat donors admitted to risk factors leading to permanent donor exclusion if revealed during the donor selection procedure (predominantly male-to-male sex and recent diagnosis of syphilis). CONCLUSION: The prevalence and incidence of TTIs among Dutch blood donors are six- to 60-fold lower than in the general Dutch population, illustrating the effectiveness of donor selection procedures. However, at least a quarter of infected donors appeared noncompliant to the donor health questionnaire (DHQ), suggesting that DHQs, or the way donor questioning is implemented, can be improved. PMID- 26355712 TI - Size-dependent specific targeting and efficient gene silencing in peritoneal macrophages using a pH-sensitive cationic liposomal siRNA carrier. AB - Macrophages are key contributors to various inflammatory diseases. Therefore, the development of an efficient in vivo short interference RNA (siRNA) system that can be delivered to macrophages represents a novel treatment strategy for addressing these disorders. It was recently revealed that peritoneal macrophages (PEMs) are involved in several diseases including ovarian cancer, and are now recognized as a promising drug target. We report herein on the use of pH sensitive cationic YSK05-MENDs as siRNA carriers and on the impact of both the size of the YSK05-MENDs and their administration routes for the efficient targeting PEMs to achieve a high level of gene silencing activity. The size of the YSK05-MENDs had a dramatic effect on their specificity for PEMs when administered intravenously, but not for intraperitoneal injection. Also, significant gene silencing was achieved by an intraperitoneal administration of the YSK05-MEND at a dose in the single digit MUg/kg range. To our knowledge, this is the most efficacious method for siRNA delivery for gene silencing in PEMs in vivo reported to date. These findings enabled us to investigate the complex function of PEMs through several gene silencing simultaneously. PMID- 26355713 TI - Revisiting the challenges of universal screening for long QT syndrome. AB - The incidence of long QT syndrome (LQTS) is generally believed to be approximately 1:2500 individuals. Given the relatively common nature of this disorder, the observation that sudden cardiac death is often a presenting symptom and the highly treatable nature of the disease, LQTS meets common criteria for the design of a universal screening program. In spite of multiple lines of evidence (international experience, cost-benefit simulations) suggesting that universal screening for LQTS is feasible and effective, there remains considerable debate and controversy surrounding the implementation of universal LQTS screening in the United States. Here, we describe some of the challenges and potential novel solutions to the practical implementation of LQTS screening. PMID- 26355714 TI - Effect of electron-donating substituent groups on aromatic ring on photoluminescence properties of complexes of benzoic acid-functionalized polysulfone with Eu(III) ions. AB - By molecular design and via polymer reactions, methoxybenzoic acid (MOBA) and hydroxybenzoic acid (HBA) were bonded onto the side chains of polysulfone (PSF) for preparing two benzoic acid-functionalized PSFs, PSF-MOBA and PSF-HBA, respectively. Based on full characterization of their structures, the two macromolecule ligands were made to coordinate to Eu(3+) ions, and two binary polymer-rare earth complexes, PSF-(MOBA)3-Eu(III) and PSF-(HBA)3-Eu(III), were obtained. At the same time, using phenanthroline (Phen) as a second small molecule ligand, the corresponding two ternary complexes, PSF-(MOBA)3-Eu(III) Phen1 and PSF-(HBA)3-Eu(III)-Phen1, were also prepared. The photo physical behaviors of these complexes were examined in depth, and the luminescent properties of these prepared polymer-rare earth complexes were mainly investigated. The experimental results show that the two electron-donating substituent groups on the aromatic ring of the bonded benzoic acid significantly affect the luminescence properties of these complexes of benzoic acid functionalized PSF and Eu(III) ions, and they can effectively strengthen the fluorescence emission intensities of the complexes. The possible reason is that through the p-pi conjugative effect, the two electron-donating substituent groups can remarkably decline the triplet state energy levels of the bonded ligand MOBA and HBA, and strengthen the matching degree of energy between the triplet state energy level of the ligand and the resonant energy level of Eu(III) ions, resulting in the enhancement of fluorescence emission intensities of the complexes. Besides, the fluorescence emissions of the binary complexes are stronger than those of the corresponding ternary complexes because of the synergistic coordination effect of Phen with the macromolecular ligand. PMID- 26355715 TI - The Reliability of Strength Tests Performed In Elevated Shoulder Positions Using a Handheld Dynamometer. AB - CONTEXT: The reliable measurement of shoulder strength is important when assessing athletes involved in overhead activities. Swimmers' shoulders are subject to repetitive humeral elevation and consequently have a high risk of developing movement-control issues and pain. Shoulder-strength tests performed in positions of elevation assist with the detection of strength deficits that may affect injury and performance. The reliability of isometric strength tests performed in positions of humeral elevation without manual stabilization, which is a typical clinical scenario, has not been established. OBJECTIVE: To establish the relative and absolute intrarater reliability of shoulder-strength tests functional to swimming in 3 body positions commonly used in the clinical setting. DESIGN: Repeated-measures reliability study. SETTING: Research laboratory. SUBJECTS: 15 university students and staff (mean +/- SD age 24 +/- 8.2 y). INTERVENTION: Isometric shoulder-strength tests were performed in positions of humeral elevation (flexion and extension in 140 degrees abduction in the scapular plane, internal and external rotation in 90 degrees abduction) on subjects without shoulder pain in supine, prone, and sitting. Subjects were tested by 1 examiner with a handheld dynamometer and retested after 48 h. MAIN OUTCOME MEASURES: Relative reliability (ICC3,1) values with 95% CI. Absolute reliability was reported by minimal detectable change (MDC). RESULTS: Good to excellent intrarater reliability was found for all shoulder-strength tests (ICC .87-.99). Intrarater reliability was not affected by body position. MDC% was <16% for every test and <=11% for tests performed in supine. CONCLUSIONS: Shoulder flexion, extension, and internal- and external-rotation strength tests performed in humeral elevation demonstrated excellent to good intrarater reliability regardless of body position. A strength change of more than 15% in any position can be considered meaningful. PMID- 26355716 TI - In vitro study on the safety of near infrared laser therapy in its potential application as postmastectomy lymphedema treatment. AB - Clinical studies demonstrated the effectiveness of laser therapy in the management of postmastectomy lymphedema, a discomforting disease that can arise after surgery/radiotherapy and gets progressively worse and chronic. However, safety issues restrict the possibility to treat cancer patients with laser therapy, since the effects of laser radiation on cancer cell behavior are not completely known and the possibility of activating postmastectomy residual cancer cells must be considered. This paper reports the results of an in vitro study aimed to investigate the effect of a class IV, dual-wavelength (808 nm and 905 nm), NIR laser system on the behavior of two human breast adenocarcinoma cell lines (namely, MCF7 and MDA-MB361 cell lines), using human dermal fibroblasts as normal control. Cell viability, proliferation, apoptosis, cell cycle and ability to form colonies were analyzed in order to perform a cell-based safety testing of the laser treatment in view of its potential application in the management of postmastectomy lymphedema. The results showed that, limited to the laser source, treatment conditions and experimental models used, laser radiation did not significantly affect the behavior of human breast adenocarcinoma cells, including their clonogenic efficiency. Although these results do not show any significant laser-induced modification of cancer cell behavior, further studies are needed to assess the possibility of safely applying NIR laser therapy for the management of postmastectomy lymphedema. PMID- 26355717 TI - A Pipeline To Enhance Ligand Virtual Screening: Integrating Molecular Dynamics and Fingerprints for Ligand and Proteins. AB - The importance of taking into account protein flexibility in drug design and virtual ligand screening (VS) has been widely debated in the literature, and molecular dynamics (MD) has been recognized as one of the most powerful tools for investigating intrinsic protein dynamics. Nevertheless, deciphering the amount of information hidden in MD simulations and recognizing a significant minimal set of states to be used in virtual screening experiments can be quite complicated. Here we present an integrated MD-FLAP (molecular dynamics-fingerprints for ligand and proteins) approach, comprising a pipeline of molecular dynamics, clustering and linear discriminant analysis, for enhancing accuracy and efficacy in VS campaigns. We first extracted a limited number of representative structures from tens of nanoseconds of MD trajectories by means of the k-medoids clustering algorithm as implemented in the BiKi Life Science Suite ( http://www.bikitech.com [accessed July 21, 2015]). Then, instead of applying arbitrary selection criteria, that is, RMSD, pharmacophore properties, or enrichment performances, we allowed the linear discriminant analysis algorithm implemented in FLAP ( http://www.moldiscovery.com [accessed July 21, 2015]) to automatically choose the best performing conformational states among medoids and X-ray structures. Retrospective virtual screenings confirmed that ensemble receptor protocols outperform single rigid receptor approaches, proved that computationally generated conformations comprise the same quantity/quality of information included in X-ray structures, and pointed to the MD-FLAP approach as a valuable tool for improving VS performances. PMID- 26355718 TI - Representation of continuous hand and arm movements in macaque areas M1, F5, and AIP: a comparative decoding study. AB - OBJECTIVE: In the last decade, multiple brain areas have been investigated with respect to their decoding capability of continuous arm or hand movements. So far, these studies have mainly focused on motor or premotor areas like M1 and F5. However, there is accumulating evidence that anterior intraparietal area (AIP) in the parietal cortex also contains information about continuous movement. APPROACH: In this study, we decoded 27 degrees of freedom representing complete hand and arm kinematics during a delayed grasping task from simultaneously recorded activity in areas M1, F5, and AIP of two macaque monkeys (Macaca mulatta). MAIN RESULTS: We found that all three areas provided decoding performances that lay significantly above chance. In particular, M1 yielded highest decoding accuracy followed by F5 and AIP. Furthermore, we provide support for the notion that AIP does not only code categorical visual features of objects to be grasped, but also contains a substantial amount of temporal kinematic information. SIGNIFICANCE: This fact could be utilized in future developments of neural interfaces restoring hand and arm movements. PMID- 26355719 TI - Percutaneous Cryoablation for Liver Cancer. AB - Based on the primary tumor site, liver cancer can be divided into two categories: (1) primary liver cancer and (2) metastatic cancer to the liver from a distant primary site. Guided cryoablation via many imaging methods induces iceball formation and tumor necrosisand is an attractive option for treating unresectable hepatocellular carcinoma (HCC) and metastatic liver cancer. There are several advantages to using cryoablation for the treatment of liver cancer: it can be performed percutaneously, intraoperatively, and laparoscopically; iceball formation can be monitored; it has little impact on nearby large blood vessels; and it induces a cryo-immunological response in situ. Clinically, primary research has shown that percutaneous cryoablation of liver cancer is relatively safe and efficient, and it can be combined with other methods, such as radiation therapy, chemotherapy, and immunology, to control disease. Although research is preliminary, cryosurgery is fast becoming an alternative treatment method for HCC or liver tumors. Here, we review the mechanisms of liver tumor cryoablation, cryoablation program selection, clinical efficiency, and complications following treatment. PMID- 26355720 TI - Isthminia panamensis, a new fossil inioid (Mammalia, Cetacea) from the Chagres Formation of Panama and the evolution of 'river dolphins' in the Americas. AB - In contrast to dominant mode of ecological transition in the evolution of marine mammals, different lineages of toothed whales (Odontoceti) have repeatedly invaded freshwater ecosystems during the Cenozoic era. The so-called 'river dolphins' are now recognized as independent lineages that converged on similar morphological specializations (e.g., longirostry). In South America, the two endemic 'river dolphin' lineages form a clade (Inioidea), with closely related fossil inioids from marine rock units in the South Pacific and North Atlantic oceans. Here we describe a new genus and species of fossil inioid, Isthminia panamensis, gen. et sp. nov. from the late Miocene of Panama. The type and only known specimen consists of a partial skull, mandibles, isolated teeth, a right scapula, and carpal elements recovered from the Pina Facies of the Chagres Formation, along the Caribbean coast of Panama. Sedimentological and associated fauna from the Pina Facies point to fully marine conditions with high planktonic productivity about 6.1-5.8 million years ago (Messinian), pre-dating the final closure of the Isthmus of Panama. Along with ecomorphological data, we propose that Isthminia was primarily a marine inhabitant, similar to modern oceanic delphinoids. Phylogenetic analysis of fossil and living inioids, including new codings for Ischyrorhynchus, an enigmatic taxon from the late Miocene of Argentina, places Isthminia as the sister taxon to Inia, in a broader clade that includes Ischyrorhynchus and Meherrinia, a North American fossil inioid. This phylogenetic hypothesis complicates the possible scenarios for the freshwater invasion of the Amazon River system by stem relatives of Inia, but it remains consistent with a broader marine ancestry for Inioidea. Based on the fossil record of this group, along with Isthminia, we propose that a marine ancestor of Inia invaded Amazonia during late Miocene eustatic sea-level highs. PMID- 26355721 TI - The effects of ankle joint strategy exercises with and without visual feedback on the dynamic balance of stroke patients. AB - [Purpose] The aim of this study was to examine the effects of visual feedback training on the balance of stroke patients performing ankle joint strategy exercises. [Subjects and Methods] In this study, 26 stroke patients were randomly and equally assigned to a visual feedback group (VFG) and a visual disuse group (VDG). They performed ankle joint strategy exercises for 30 minutes, three times per week for six weeks. The patients' balance ability was measured before and after the exercises to compare the effects of visual feedback. To assess balance ability, the limits of stability (LOS) and the distance the center of pressure (CoP) moved were measured using a BT4 portable force platform. The Berg balance scale (BBS) and the timed up and go (TUG) test were also used to assess balance before and after the exercises. [Results] Changes in LOS were significant in the anterior, posterior, left, and right directions in each group, and the interactions between the two groups were significant in the posterior, left, and right directions. The changes in TUG and BBS results between pre-test and the post-test were statistically significant in the two groups, and also between the groups. [Conclusion] Visual feedback training had a positive effect on balance when ankle joint strategy exercises were performed by stroke patients to improve balance. PMID- 26355722 TI - Antimicrobial films containing microparticles for the enhancement of long-term sustained release. AB - Coated packagings with thin films containing antimicrobial agents are an alternative technology to ensure the protection of products against microbial contaminations. Indeed, they allow lowering the antimicrobial concentration in the bulk of the product while meeting the safety requirements and the growing consumer demand for low preservative concentrations. Microencapsulation is a suitable way for controlling active agent release and providing a long-term activity. This work aims at combining both technical solutions with coatings containing antimicrobial microparticles for the achievement of long-term sustained release. Polyethylene surfaces were functionalized with microparticles of poly(methyl methacrylate) (PMMA) loaded with phenylethyl alcohol (PEA) as antimicrobial agent by the dip coating process using a polyurethane binder. The release of PEA into water from coated polyethylene surfaces and from PMMA microparticles was investigated to assess the sustained release and its mechanisms. Films with various thicknesses of 400-1000 um containing antimicrobial microparticles demonstrated unusual long-term release longer than 3 months. The diffusion of the antimicrobial agent through PMMA was the rate limiting step of the sustained release. PEA release increased as the contact area of the protruding microparticles with the external medium increased and the thickness of the film decreased. Such antimicrobial agents encapsulated inside thin coatings are promising with regards to antimicrobial preservation of products along their full shelf-life. PMID- 26355723 TI - Repeated Intravenous Treatment with Recombinant Tissue-Type Plasminogen Activator in Patients with Acute Ischemic Stroke. AB - OBJECTIVE: Increased use of systemic thrombolysis, demographic changes, and higher chances of surviving first-ever strokes all lead to an increasing number of patients with recurrent stroke. However, data on repeated thrombolysis are limited. Here, we report on the safety and clinical effects of repeated intravenous recombinant tissue-type plasminogen activator (rt-PA) treatment in a large consecutive cohort of stroke patients. METHODS: We identified all stroke patients who received repeated thrombolysis. We determined safety and 3-month clinical outcome after the first and second thrombolysis. All patients received follow-up brain imaging. Good clinical outcome was defined as a modified Rankin Scale of 0-2 or recovery to the prestroke status. RESULTS: In total, 24 patients were included (i.e. 1.5% of all stroke patients treated with rt-PA at our center who survived the first treatment; male 45.8%; median age at first event: 74.5 years). No allergic or anaphylactic reactions were recorded after the first time of treatment, but oral angioedema developed once during the second treatment. No symptomatic intracerebral hemorrhage was observed. Clinical outcome was good in 75.0% after the first, but in only 41.7% after the second treatment (p = 0.021). CONCLUSIONS: Repeated thrombolysis was not associated with a higher rate of complications. However, the clinical outcome appears to be less satisfactory than after the first treatment. PMID- 26355724 TI - Multicomponent ternary cocrystals of the sulfonamide group with pyridine-amides and lactams. AB - SMBA was selected as a bifunctional sulfa drug to design ternary cocrystals with pyridine amides and lactam coformers. Supramolecular assembly of five ternary cocrystals of p-sulfonamide benzoic acid with nicotinamide and 2-pyridone is demonstrated and reproducible heterosynthons are identified for crystal engineering. PMID- 26355726 TI - The Association Between Insomnia and Increased Future Cardiovascular Events: A Nationwide Population-Based Study. AB - OBJECTIVES: Insomnia may increase the risk of cardiovascular disease (CVD), but the reported magnitude of the associations between sleep characteristics and CVD is inconsistent. We investigated the association between insomnia and the risk of developing acute myocardial infarction (AMI) and/or stroke by using a nationwide, population-based cohort database in Taiwan. METHODS: The analyses were conducted using information from a random sample of 1 million people enrolled in the nationally representative Taiwan National Health Insurance Research Database. A total of 44,080 individuals who were 20 years or older, including 22,040 people who had diagnosis of insomnia during the study period and an age-, sex-, comorbidity-matched group of 22,040 people without insomnia, were enrolled in our study. The study end points were the occurrence of cardiovascular events including AMI or stroke during follow-up. RESULTS: During a 10-year follow-up, 302 AMI events and 1049 stroke events were identified. The insomnia group had a higher incidence of AMI (2.25 versus 1.08 per 1000 person-years) and stroke (8.01 versus 3.69 per 1000 person-years, p < .001). Cox proportional hazard regression model analysis showed that insomnia was independently associated with a higher risk of future AMI (hazard ratio [HR] = 1.68, 95% confidence interval [CI] = 1.31 2.16, p < .001), stroke (HR = 1.85, 95% CI = 1.62-2.12, p < .001), and the composite event index (HR = 1.81, 95% CI = 1.61-2.05, p < .001), after adjusting for age, sex, and comorbidities. CONCLUSIONS: Insomnia is associated with an increased risk of future cardiovascular events. PMID- 26355727 TI - Clinical and Prognostic Value of Depressive Symptoms and N-Terminal Pro-B-Type Natriuretic Peptide in Patients With Eisenmenger Syndrome. AB - OBJECTIVES: Eisenmenger syndrome (ES) is commonly associated with depressive symptoms and elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP). We investigated the predictive value of depressive symptoms and NTproBNP levels for long-term outcomes in patients with ES. METHODS: Blood was drawn to measure NT proBNP, and depressive symptoms were measured using the Korean version of the Beck Depression Inventory (BDI) in an outpatient clinic sample of 64 patients with ES (67% female; median age = 41.5 years [range, 21.0-74.8 years]). Cardiac events (hospitalization, emergency department visits, and cardiac death) were monitored during 3 years of follow-up. RESULTS: During the follow-up period, 15 (23.4%) patients experienced a cardiac event. The combination of depressive symptoms and NT-proBNP levels better predicted future cardiac events than either variable alone. Patients with NT-proBNP > 510 pg/ml and a total BDI score > 10 had a 9.6 times higher risk for cardiac events than did patients with NT-proBNP <= 510 pg/ml or total BDI score <= 10 (p < .001). CONCLUSIONS: Depressive symptoms and NT-proBNP levels are both associated with adverse clinical outcomes in ES. PMID- 26355725 TI - Prophylactic Subacute Administration of Zinc Increases CCL2, CCR2, FGF2, and IGF 1 Expression and Prevents the Long-Term Memory Loss in a Rat Model of Cerebral Hypoxia-Ischemia. AB - Prophylactic subacute administration of zinc decreases lipoperoxidation and cell death following a transient cerebral hypoxia-ischemia, thus suggesting neuroprotective and preconditioning effects. Chemokines and growth factors are also involved in the neuroprotective effect in hypoxia-ischemia. We explored whether zinc prevents the cerebral cortex-hippocampus injury through regulation of CCL2, CCR2, FGF2, and IGF-1 expression following a 10 min of common carotid artery occlusion (CCAO). Male rats were grouped as follows: (1) Zn96h, rats injected with ZnCl2 (one dose every 24 h during four days); (2) Zn96h + CCAO, rats treated with ZnCl2 before CCAO; (3) CCAO, rats with CCAO only; (4) Sham group, rats with mock CCAO; and (5) untreated rats. The cerebral cortex hippocampus was dissected at different times before and after CCAO. CCL2/CCR2, FGF2, and IGF-1 expression was assessed by RT-PCR and ELISA. Learning in Morris Water Maze was achieved by daily training during 5 days. Long-term memory was evaluated on day 7 after learning. Subacute administration of zinc increased expression of CCL2, CCR2, FGF2, and IGF-1 in the early and late phases of postreperfusion and prevented the CCAO-induced memory loss in the rat. These results might be explained by the induction of neural plasticity because of the expression of CCL2 and growth factors. PMID- 26355732 TI - Capsule Endoscopy in the Assessment of Obscure Gastrointestinal Bleeding: An Economic Analysis. AB - BACKGROUND: Small-bowel capsule endoscopy is a tool used to visualize the small bowel to identify the location of bleeds in obscure gastrointestinal bleeding (OGIB). Capsule endoscopy is currently funded in Ontario in cases where there has been a failure to identify a source of bleeding via conventional diagnostic procedures. In Ontario, capsule endoscopy is a diagnostic option for patients whose findings on esophagogastroduodenoscopy, colonoscopy, and push enteroscopy have been negative (i.e., the source of bleeding was not found). OBJECTIVES: This economic analysis aims to estimate the budget impact of different rates of capsule endoscopy use as a complement to push enteroscopy procedures in patients aged 18 years and older. DATA SOURCES: Population-based administrative databases for Ontario were used to identify patients receiving push enteroscopy and small bowel capsule endoscopy in the fiscal years 2008 to 2012. REVIEW METHODS: A systematic literature search was performed to identify economic evaluations of capsule endoscopy for the investigation of OGIB. Studies were assessed for their methodological quality and their applicability to the Ontarian setting. An original budget impact analysis was performed using data from Ontarian administrative sources and published literature. The budget impact was estimated for different levels of use of capsule endoscopy as a complement to push enteroscopy due to the uncertain clinical utility of the capsule based on current clinical evidence. The analysis was conducted from the provincial public payer perspective. RESULTS: With varying rates of capsule endoscopy use, the budgetary impact spans from savings of $510,000, when no (0%) push enteroscopy procedures are complemented with capsule endoscopy, to $2,036,000, when all (100%) push enteroscopy procedures are complemented with capsule endoscopy. A scenario where 50% of push enteroscopy procedures are complemented with capsule endoscopy (expected use based on expert opinion) would result in additional expenditure of about $763,000. LIMITATIONS: In the literature on OGIB, estimates of rebleeding rates after endoscopic procedures or spontaneous cessation rates are unreliable, with a lack of data. Rough estimates from expert consultation can provide an indication of expected additional use of capsule endoscopy; however, a wide range of capsule uses was explored. CONCLUSIONS: The budgetary impact in the first year in Ontario of capsule endoscopy use to complement push enteroscopy procedures ranges from $510,000 in savings to an additional expenditure of $2,036,000 (at 0% and 100% push enteroscopy procedures complemented, respectively). The expected scenario of 50% of push enteroscopy procedures likely to benefit from the use of capsule endoscopy, based on expert opinion, would result in additional expenditures of $763,000 in the first year. PMID- 26355734 TI - Errata: Vol. 61, No. 9. AB - In the report, "Vital Signs: Preventing Clostridium difficile Infections," published in 2012, several errors occurred in the text and in a figure title and alternate text. A Notice to Readers about this report has been published in this issue of MMWR. PMID- 26355733 TI - iRGD-conjugated DSPE-PEG2000 nanomicelles for targeted delivery of salinomycin for treatment of both liver cancer cells and cancer stem cells. AB - AIMS: To develop novel iRGD (internalizing Arg-Gly-Asp peptide)-conjugated DSPE PEG2000 nanomicelles (M-SAL-iRGD) for delivery of salinomycin to both liver cancer cells and cancer stem cells (CSCs). MATERIALS & METHODS: The characterization, antitumor activity and mechanism of action of M-SAL-iRGD were evaluated. RESULTS & CONCLUSION: M-SAL-iRGD possessed a small size of around 10 nm, and drug encapsulation efficacy higher than 90%. M-SAL-iRGD showed significantly increased cytotoxic effect toward both nontargeted M-SAL (salinomycin-loaded DSPE-PEG2000 nanomicelles) and salinomycin in both liver cancer cells and CSCs. The tissue distribution and antitumor assays in mice bearing liver cancer xenograft confirmed the superior penetration tumor efficacy and antitumor activity of M-SAL-iRGD. M-SAL-iRGD represent a potential effective nanomedicine against liver cancer. PMID- 26355736 TI - Editorial. PMID- 26355737 TI - Combinatorial hematopoietic stem cell transplantation and vaccination reduces viral pathogenesis following SHIV89.6P-challenge. AB - Development of curative approaches for HIV-1 infected patients requires novel approaches aimed at eliminating viral reservoirs and replacing potential target cells with infection-resistant immune cell populations. We have previously shown that autologous transplantation of genetically modified hematopoietic stem cells (HSCs) with lentiviral vectors encoding the mC46-fusion inhibitor results in a significant reduction in viral pathogenesis following challenge with the highly pathogenic dual tropic, SHIV89.6P strain. In this study, we used a combinatorial approach in which following engraftment of genetically modified HSCs, pigtailed macaques were vaccinated with a previously developed vaccinia-based vaccine expressing SIV-Gag, Pol. Using this dual therapy approach, lower viremia was detected in both the acute and chronic phase of disease with levels reaching near the lower limits of detection. In comparison with macaques receiving HSCT only, the combination approach resulted in a further log decrease in plasma viremia. Similar to our previous studies, positive selection of all CD4(+) T-cell subsets was observed; however, higher gene-modified CD4(+) T-cell levels were observed during the chronic phase when vaccination was included suggesting that combining vaccination with HSCT may lower the necessary threshold for achieving viremic control. PMID- 26355738 TI - Overweight and obesity in children with newly diagnosed inflammatory bowel disease. AB - PURPOSE: Determination of overweight and obesity prevalence in children with inflammatory bowel disease (IBD) at the time of diagnosis. MATERIAL AND METHODS: This was a multicenter retrospective study. The study group consisted of children with new cases of IBD diagnosed in 2005-2013 according to the Porto criteria. Hospital admission records were reviewed for demographic and clinical characteristics. BMI-for-age and gender percentile charts were used to define overweight as >=85th BMI percentile and obesity as >=95th BMI percentile. RESULTS: 675 patients were evaluated: 368 with Crohn's disease (CD) and 307 with ulcerative colitis (UC). Of these, 54.8% were boys and 45.2% were girls. There were no statistically significant differences in age, weight, height and disease activity between the CD and UC patients. The UC patients had higher BMI values than the CD patients. The prevalence of overweight and obesity was higher in the UC than the CD patients (4.89% CI95 2.76-7.93 vs. 2.45% CI95 1.12-4.59 and 8.47% CI95 5.61-12.16 vs. 1.9% CI95 0.77-3.88, respectively); the differences were statistically significant (-2.44% CI95 -5.45 to 0.49 and -6.57% CI95 -10 to -3.1, respectively). The risk of overweight/obesity was 3.5 times higher for patients with UC (OR=0.272, CI95 0.14-0.49, p=0.0004). CONCLUSIONS: The prevalence of overweight and obesity in newly diagnosed children with IBD was 8.4% and was higher in patients with UC than in patients with CD. The results of this study have shown that not only malnourished children may suffer from IBD but also children who are overweight or obese at the time of diagnosis. PMID- 26355739 TI - Computational simulation of carotid stenosis and flow dynamics based on patient ultrasound data - A new tool for risk assessment and surgical planning. AB - PURPOSE: There is nowadays extensive experimental and computational investigation on the pathophysiology of atherosclerosis, searching correlations between its focal nature and local hemodynamic environment. The goal of this work is to present a methodology for patient-specific hemodynamics study of the carotid artery bifurcation based on the use of ultrasound (US) morphological and blood flow velocity patient data. MATERIALS/METHODS: Subject-specific studies were performed for two patients, using a developed finite element code. Geometrical models were obtained from the acquisition of longitudinal and sequential cross sectional ultrasound images and boundary conditions from Doppler velocity measurements at the common carotid artery. RESULTS: There was a good agreement between ultrasound imaging data and computational simulated results. For a normal and a stenosed carotid bifurcation the velocity, wall shear stress (WSS) and WSS descriptors analysis illustrated the extremely complex hemodynamic behavior along the cardiac cycle. Different patterns were found, associated with morphology and hemodynamic patient-specific conditions. High values of time-averaged WSS (TAWSS) were found at stenosis site and for both patients TAWSS fields presented low values within areas of high oscillating shear index and relative residence time values, corresponding to recirculation zones. CONCLUSION: Simulated hemodynamic parameters were able to capture the disturbed flow conditions in a normal and a stenosed carotid artery bifurcation, which play an important role in the development of local atherosclerotic plaques. Computational simulations based on clinic US might help improving diagnostic and treatment management of carotid atherosclerosis. PMID- 26355740 TI - Characterization Method for 3D Substructure of Nuclear Cell Based on Orthogonal Phase Images. AB - A set of optical models associated with blood cells are introduced in this paper. All of these models are made up of different parts possessing symmetries. The wrapped phase images as well as the unwrapped ones from two orthogonal directions related to some of these models are obtained by simulation technique. Because the phase mutation occurs on the boundary between nucleus and cytoplasm as well as on the boundary between cytoplasm and environment medium, the equation of inflexion curve is introduced to describe the size, morphology, and substructure of the nuclear cell based on the analysis of the phase features of the model. Furthermore, a mononuclear cell model is discussed as an example to verify this method. The simulation result shows that characterization with inflexion curve based on orthogonal phase images could describe the substructure of the cells availably, which may provide a new way to identify the typical biological cells quickly without scanning. PMID- 26355741 TI - Correction: Prevalence and Molecular Characterization of Glucose-6-Phosphate Dehydrogenase Deficiency at the China-Myanmar Border. AB - [This corrects the article DOI: 10.1371/journal.pone.0134593.]. PMID- 26355742 TI - Parental Midlife Body Shape and Association with Multiple Adult Offspring Obesity Measures: North West Adelaide Health Study. AB - There is compelling evidence that parental weight is a strong determinant of offspring weight status. The study used cross-sectional self-reported and measured data from a longitudinal cohort of Australian adults (n = 2128) from Stage 3 (2008-10) of the North West Adelaide Health Study (1999-2003, baseline n = 4056) to investigate the association between midlife parental body shape and four indicators of obesity and fat distribution. The analysis used measured body mass index (BMI), waist circumference (WC), waist hip ratio (WHR) and waist height ratio (WHtR) of adult offspring, together with pictograms for recall of parental body shape. Compared to both parents being a healthy weight, offspring were more likely to be overweight or obese if both parents were an unhealthy weight at age 40 (OR 2.14, 95% CI 1.67-2.76) and further, those participants whose mother was an unhealthy weight were more likely to be overweight or obese themselves (OR 1.50, 95% CI 1.14-1.98). There were similar but lower results for those with an overweight/obese father (OR 1.44, 95% CI 1.08-1.93). The effect of one or both parents being overweight or obese tended to be stronger for daughters than for sons across BMI, WC and WHtR. BMI showed the strongest association with parental body shape (OR 2.14), followed by WC (OR 1.78), WHtR (OR 1.71) and WHR (OR 1.45). WHtR (42-45%) and BMI (35-36%) provided the highest positive predictive values for overweight/obesity from parental body shape. Parental obesity increases the risk of obesity for adult offspring, both for overall body shape and central adiposity, particularly for daughters. Pictograms could potentially be used as a screening tool in primary care settings to promote healthy weight among young adults. PMID- 26355743 TI - Effect of Flow Rate on In Vitro Aerodynamic Performance of NEXThaler((r)) in Comparison with Diskus((r)) and Turbohaler((r)) Dry Powder Inhalers. AB - BACKGROUND: European and United States Pharmacopoeia compendial procedures for assessing the in vitro emitted dose and aerodynamic size distribution of a dry powder inhaler require that 4.0 L of air at a pressure drop of 4 kPa be drawn through the inhaler. However, the product performance should be investigated using conditions more representative of what is achievable by the patient population. This work compares the delivered dose and the drug deposition profile at different flow rates (30, 40, 60, and 90 L/min) of Foster NEXThaler((r)) (beclomethasone dipropionate/formoterol fumarate), Seretide((r)) Diskus((r)) (fluticasone propionate/salmeterol xinafoate), and Symbicort((r)) Turbohaler((r)) (budesonide/formoterol fumarate). METHODS: The delivered dose uniformity was tested using a dose unit sampling apparatus (DUSA) at inhalation volumes either 2.0 or 4.0 L and flow rates 30, 40, 60, or 90 L/min. The aerodynamic assessment was carried out using a Next Generation Impactor by discharging each inhaler at 30, 40, 60, or 90 L/min for a time sufficient to obtain an air volume of 4 L. RESULTS: Foster((r)) NEXThaler((r)) and Seretide((r)) Diskus((r)) showed a consistent dose delivery for both the drugs included in the formulation, independently of the applied flow rate. Contrary, Symbicort((r)) Turbohaler((r)) showed a high decrease of the emitted dose for both budesonide and formoterol fumarate when the device was operated at airflow rate lower that 60 L/min. The aerosolizing performance of NEXThaler((r)) and Diskus((r)) was unaffected by the flow rate applied. Turbohaler((r)) proved to be the inhaler most sensitive to changes in flow rate in terms of fine particle fraction (FPF) for both components. Among the combinations tested, Foster NEXThaler((r)) was the only one capable to deliver around 50% of extra-fine particles relative to delivered dose. CONCLUSIONS: NEXThaler((r)) and Diskus((r)) were substantially unaffected by flow rate through the inhaler in terms of both delivered dose and fine particle mass. PMID- 26355744 TI - Antivenoms for Snakebite Envenoming: What Is in the Research Pipeline? PMID- 26355745 TI - Assessment of the Incremental Benefit of Computer-Aided Detection (CAD) for Interpretation of CT Colonography by Experienced and Inexperienced Readers. AB - OBJECTIVES: To quantify the incremental benefit of computer-assisted-detection (CAD) for polyps, for inexperienced readers versus experienced readers of CT colonography. METHODS: 10 inexperienced and 16 experienced radiologists interpreted 102 colonography studies unassisted and with CAD utilised in a concurrent paradigm. They indicated any polyps detected on a study sheet. Readers' interpretations were compared against a ground-truth reference standard: 46 studies were normal and 56 had at least one polyp (132 polyps in total). The primary study outcome was the difference in CAD net benefit (a combination of change in sensitivity and change in specificity with CAD, weighted towards sensitivity) for detection of patients with polyps. RESULTS: Inexperienced readers' per-patient sensitivity rose from 39.1% to 53.2% with CAD and specificity fell from 94.1% to 88.0%, both statistically significant. Experienced readers' sensitivity rose from 57.5% to 62.1% and specificity fell from 91.0% to 88.3%, both non-significant. Net benefit with CAD assistance was significant for inexperienced readers but not for experienced readers: 11.2% (95%CI 3.1% to 18.9%) versus 3.2% (95%CI -1.9% to 8.3%) respectively. CONCLUSIONS: Concurrent CAD resulted in a significant net benefit when used by inexperienced readers to identify patients with polyps by CT colonography. The net benefit was nearly four times the magnitude of that observed for experienced readers. Experienced readers did not benefit significantly from concurrent CAD. PMID- 26355746 TI - Shotgun assembly of the first mitochondrial genome of Metapenaeus (Metapenaeus ensis) with phylogenetic consideration. AB - The first complete mitochondrial genome sequence of Metapenaeus was characterized from sand shrimp Metapenaeus ensis using shotgun assembly method. The complete mitochondrial DNA sequence is a 15 944 bp circular molecule, and contains 13 protein-coding genes, 22 transfer RNA genes, two rRNA genes, and a control region. The gene arrangements are consistent with the pancrustacean ground pattern. The phylogenetic trees were divided two clades besides outgroup, which belonged to Penaeus s.l. and Metapenaeus genus. The molecular analyses provided robust evidence for the monophyly of Fenneropenaeus, but Litopenaeus is not monophyletic. PMID- 26355748 TI - Dynamic entangled framework based on an iridium-organic unit showing reversible luminescence turn-on sensing. AB - A new entangled metal-organic framework shows reversible structural dynamics and luminescence changing in response to the loss of guest H2O molecules. Furthermore, an intense and sensitive luminescence turn-on sensing was observed by the naked eye for 1 upon detection of the volatile organic solvent molecule CH3CN, accompanied by reversible structural transformation. PMID- 26355747 TI - The Role of Vertical and Horizontal Transfer in the Evolutionary Dynamics of PIF Like Transposable Elements in Triticeae. AB - PIF-like transposable elements are members of the PIF/Harbinger superfamily of DNA transposons found in the genomes of many plants, animals, and fungi. The evolution of the gene that encodes the transposase responsible for mobilizing PIF like elements has been studied in both plants and animals, but the elements' history in flowering plants remains poorly known. In this work, we describe the phylogenetic distribution and evolution of PIF-like elements in the genomes of 21 diploid species from the wheat tribe, Triticeae, and we present the first convincing evidence of horizontal transfer of PIF elements in plant genomes. A phylogenetic analysis of 240 PIF sequences based on the conserved region of the transposase domain revealed at least four main transposase lineages. Their complex evolutionary history can be best explained by a combination of vertical transmission with differential evolutionary success among lineages, and occasional horizontal transfer between phylogenetically distant Triticeae genera. In addition, we identified 127 potentially functional transposase sequences indicating possible recent activity of PIF. PMID- 26355749 TI - Characterization of an Additional Splice Acceptor Site Introduced into CYP4B1 in Hominoidae during Evolution. AB - CYP4B1 belongs to the cytochrome P450 family 4, one of the oldest P450 families whose members have been highly conserved throughout evolution. The CYP4 monooxygenases typically oxidize fatty acids to both inactive and active lipid mediators, although the endogenous ligand(s) is largely unknown. During evolution, at the transition of great apes to humanoids, the CYP4B1 protein acquired a serine instead of a proline at the canonical position 427 in the meander region. Although this alteration impairs P450 function related to the processing of naturally occurring lung toxins, a study in transgenic mice suggested that an additional serine insertion at position 207 in human CYP4B1 can rescue the enzyme stability and activity. Here, we report that the genomic insertion of a CAG triplet at the intron 5-exon 6 boundary in human CYP4B1 introduced an additional splice acceptor site in frame. During evolution, this change occurred presumably at the stage of Hominoidae and leads to two major isoforms of the CYP4B1 enzymes of humans and great apes, either with or without a serine 207 insertion (insSer207). We further demonstrated that the CYP4B1 enzyme with insSer207 is the dominant isoform (76%) in humans. Importantly, this amino acid insertion did not affect the 4-ipomeanol metabolizing activities or stabilities of the native rabbit or human CYP4B1 enzymes, when introduced as transgenes in human primary cells and cell lines. In our 3D modeling, this functional neutrality of insSer207 is compatible with its predicted location on the exterior surface of CYP4B1 in a flexible side chain. Therefore, the Ser207 insertion does not rescue the P450 functional activity of human CYP4B1 that has been lost during evolution. PMID- 26355750 TI - Relationships of wild and domesticated rices (Oryza AA genome species) based upon whole chloroplast genome sequences. AB - Rice is the most important crop in the world, acting as the staple food for over half of the world's population. The evolutionary relationships of cultivated rice and its wild relatives have remained contentious and inconclusive. Here we report on the use of whole chloroplast sequences to elucidate the evolutionary and phylogenetic relationships in the AA genome Oryza species, representing the primary gene pool of rice. This is the first study that has produced a well resolved and strongly supported phylogeny of the AA genome species. The pan tropical distribution of these rice relatives was found to be explained by long distance dispersal within the last million years. The analysis resulted in a clustering pattern that showed strong geographical differentiation. The species were defined in two primary clades with a South American/African clade with two species, O glumaepatula and O longistaminata, distinguished from all other species. The largest clade was comprised of an Australian clade including newly identified taxa and the African and Asian clades. This refined knowledge of the relationships between cultivated rice and the related wild species provides a strong foundation for more targeted use of wild genetic resources in rice improvement and efforts to ensure their conservation. PMID- 26355751 TI - Cross Platform Standardisation of an Experimental Pipeline for Use in the Identification of Dysregulated Human Circulating MiRNAs. AB - INTRODUCTION: Micro RNAs (miRNAs) are a class of highly conserved small non coding RNAs that play an important part in the post-transcriptional regulation of gene expression. A substantial number of miRNAs have been proposed as biomarkers for diseases. While reverse transcriptase Real-time PCR (RT-qPCR) is considered the gold standard for the evaluation and validation of miRNA biomarkers, small RNA sequencing is now routinely being adopted for the identification of dysregulated miRNAs. However, in many cases where putative miRNA biomarkers are identified using small RNA sequencing, they are not substantiated when RT-qPCR is used for validation. To date, there is a lack of consensus regarding optimal methodologies for miRNA detection, quantification and standardisation when different platform technologies are used. MATERIALS AND METHODS: In this study we present an experimental pipeline that takes into consideration sample collection, processing, enrichment, and the subsequent comparative analysis of circulating small ribonucleic acids using small RNA sequencing and RT-qPCR. RESULTS, DISCUSSION, CONCLUSIONS: Initially, a panel of miRNAs dysregulated in circulating blood from breast cancer patients compared to healthy women were identified using small RNA sequencing. MiR-320a was identified as the most dysregulated miRNA between the two female cohorts. Total RNA and enriched small RNA populations (<30 bp) isolated from peripheral blood from the same female cohort samples were then tested for using a miR-320a RT-qPCR assay. When total RNA was analysed with this miR-320a RT-qPCR assay, a 2.3-fold decrease in expression levels was observed between blood samples from healthy controls and breast cancer patients. However, upon enrichment for the small RNA population and subsequent analysis of miR-320a using RT-qPCR, its dysregulation in breast cancer patients was more pronounced with an 8.89-fold decrease in miR-320a expression. We propose that the experimental pipeline outlined could serve as a robust approach for the identification and validation of small RNA biomarkers for disease. PMID- 26355752 TI - Health Beliefs Related to Diabetes Mellitus Prevention among Adolescents in Saudi Arabia. AB - OBJECTIVES: The incidence of type 2 diabetes mellitus (T2DM) is growing rapidly in the Saudi population. The purpose of this study was to assess the constructs of the health belief model (HBM) as they relate to T2DM lifestyle and prevention behaviours among adolescents. METHODS: A cross-sectional study was conducted between May and October 2013 among 426 non-diabetic secondary school students from randomly selected schools in Riyadh, Saudi Arabia. An Arabic version of an adapted English language questionnaire was used to assess knowledge and attitudes related to the severity and prevention of T2DM. A preventative behaviour assessment was also conducted to assess physical activity and dietary habits. RESULTS: The majority of the students (63.4%) had at least one diabetic family member. Obesity was more frequent in males compared to females (P = 0.013). Awareness about the importance of maintaining a healthy body weight to prevent T2DM was lower in males than females (P = 0.037), although males engaged in routine exercise more often (P = 0.001). Males were less likely than females to recognise the risks for T2DM, including obesity (P = 0.030), heredity (P = 0.013) and high fat intake (P = 0.001). CONCLUSION: An alarmingly high number of Saudi students were unaware of T2DM severity and associated risk factors. Female students were more aware of the benefits of T2DM preventative lifestyle behaviours than males, although males engaged in routine exercise more often. Raising adolescents' awareness about the primary prevention strategies for T2DM should be a public health priority in Saudi Arabia. The HBM could inform further research on diabetes prevention among Saudi adolescents. PMID- 26355753 TI - Functional nicotinic acetylcholine receptor reconstitution in Au(111)-supported thiolipid monolayers. AB - The insertion and function of the muscle-type nicotinic acetylcholine receptor (nAChR) in Au(111)-supported thiolipid self-assembled monolayers have been studied by atomic force microscopy (AFM), surface plasmon resonance (SPR), and electrochemical techniques. It was possible for the first time to resolve the supramolecular arrangement of the protein spontaneously inserted in a thiolipid monolayer in an aqueous solution. Geometric supramolecular arrays of nAChRs were observed, most commonly in a triangular form compatible with three nAChR dimers of ~20 nm each. Addition of the full agonist carbamoylcholine activated and opened the nAChR ion channel, as revealed by the increase in capacitance relative to that of the nAChR-thiolipid system under basal conditions. Thus, the self assembled system appears to be a viable biomimetic model to measure ionic conductance mediated by ion-gated ion channels under different experimental conditions, with potential applications in biotechnology and pharmacology. PMID- 26355754 TI - Inpatient Use of Computer-Guided Insulin Devices Moving into the Non-Intensive Care Unit Setting. PMID- 26355755 TI - Possible Computer Model for Predicting Cardiovascular Disease in Type 2 Diabetes. PMID- 26355757 TI - Potential Insulin Underdelivery from Prefilled and Reusable Insulin Pens in Cases of Premature Needle Withdrawal: A Laboratory Evaluation. AB - BACKGROUND: Devices for the treatment of diabetes are not always used as recommended in good practice. Our aim was to evaluate potential insulin underdelivery in cases of premature needle withdrawal after injection with insulin pens, which is a commonly observed misuse, especially in young type 1 diabetes patients. MATERIALS AND METHODS: Potential insulin underdelivery was evaluated using five prefilled insulin pens (lispro Kwikpen((r)) [Eli Lilly, Indianapolis, IN], aspart Flexpen((r)) [Novo Nordisk, Bagsvaerd, Denmark], glulisine Solostar((r)) [Sanofi, Paris, France], detemir Flexpen((r)) [Novo Nordisk], and glargine Solostar((r)) [Sanofi]) and three reusable insulin pens (Humapen((r)) Luxura HD with lispro cartridge [Eli Lilly], Novopen((r)) Echo with aspart and detemir cartridge [Novo Nordisk], and JuniorSTAR((r)) with glulisine and glargine cartridge [Sanofi]) in a laboratory. For each pen and insulin, we simulated premature needle withdrawal 2 and 3 s after an insulin injection of 5 and 10 units, respectively. RESULTS: With prefilled pens, mean potential insulin underdelivery was 0.43+/-0.30 and 0.44+/-0.32 units after injection of 5 and 10 units, respectively. With reusable pens, mean potential insulin underdelivery was lower (0.29+/-0.13 and 0.29+/-0.12 units after injection of 5 and 10 units, respectively; P<0.001). The results were heterogeneous across pens, ranging from 2.6%/1.6% to 20.2%/8.6% of the selected insulin dose for prefilled/reusable pens, respectively (P<0.001). CONCLUSIONS: Potential insulin underdelivery varies across prefilled and reusable insulin pens but may represent up to one-fifth of the total injected dose. Clinicians should be aware of the potential consequences of premature needle withdrawal and should reinforce insulin injection education. PMID- 26355756 TI - Standardized Glycemic Management with a Computerized Workflow and Decision Support System for Hospitalized Patients with Type 2 Diabetes on Different Wards. AB - BACKGROUND: This study investigated the efficacy, safety, and usability of standardized glycemic management by a computerized decision support system for non-critically ill hospitalized patients with type 2 diabetes on four different wards. MATERIALS AND METHODS: In this open, noncontrolled intervention study, glycemic management of 99 patients with type 2 diabetes (62% acute admissions; 41 females; age, 67+/-11 years; hemoglobin A1c, 65+/-21 mmol/mol; body mass index, 30.4+/-6.5 kg/m(2)) on clinical wards (Cardiology, Endocrinology, Nephrology, Plastic Surgery) of a tertiary-care hospital was guided by GlucoTab((r)) (Joanneum Research GmbH [Graz, Austria] and Medical University of Graz [Graz, Austria]), a mobile decision support system providing automated workflow support and suggestions for insulin dosing to nurses and physicians. RESULTS: Adherence to insulin dosing suggestions was high (96.5% bolus, 96.7% basal). The primary outcome measure, percentage of blood glucose (BG) measurements in the range of 70 140 mg/dL, occurred in 50.2+/-22.2% of all measurements. The overall mean BG level was 154+/-35 mg/dL. BG measurements in the ranges of 60-70 mg/dL, 40-60 mg/dL, and <40 mg/dL occurred in 1.4%, 0.5%, and 0.0% of all measurements, respectively. A regression analysis showed that acute admission to the Cardiology Ward (+30 mg/dL) and preexisting home insulin therapy (+26 mg/dL) had the strongest impact on mean BG. Acute admission to other wards had minor effects (+4 mg/dL). Ninety-one percent of the healthcare professionals felt confident with GlucoTab, and 89% believed in its practicality and 80% in its ability to prevent medication errors. CONCLUSIONS: An efficacious, safe, and user-accepted implementation of GlucoTab was demonstrated. However, for optimized personalized patient care, further algorithm modifications are required. PMID- 26355758 TI - Evaluating Laboratory Performance on Point-of-Care Glucose Testing with Six Sigma Metric for 151 Institutions in China. AB - BACKGROUND: The aim of this study was to use Six Sigma(SM) (Motorola Trademark Holdings, Libertyville, IL) techniques to analyze the quality of point-of-care (POC) glucose testing measurements quantitatively and to provide suggestions for improvement. MATERIALS AND METHODS: In total, 151 laboratories in China were included in this investigation in 2014. Bias and coefficient of variation were collected from an external quality assessment and an internal quality control program, respectively, for POC glucose testing organized by the National Center for Clinical Laboratories. The sigma values and the Quality Goal Index were used to evaluate the performance of POC glucose meters. RESULTS: There were 27, 30, 57, and 37 participants in the groups using Optium XceedTM (Abbott Diabetes Care, Alameda, CA), Accu-Chek((r)) Performa (Roche, Basel, Switzerland), One Touch Ultra((r)) (Abbott), and "other" meters, respectively. The median of the absolute value of percentage difference varied among different lots and different groups. Among all the groups, the Abbott One Touch Ultra group had the smallest median of absolute value of percentage difference except for lot 201411, whereas the "other" group had the largest median in all five lots. More than 85% of participate laboratories satisfied the total allowable error (TEa) requirement in International Organization for Standardization standard 15197:2013, and 85.43% (129/151) of laboratories obtained intralaboratory coefficient of variations less than 1/3TEa. However, Six Sigma techniques suggested that 41.72% (63/151) to 65.56% (99/151) of the laboratories needed to improve their POC glucose testing performance, in either precision, trueness, or both. CONCLUSIONS: Laboratories should pay more attention on the practice of POC glucose testing and take actions to improve their performance. Only in this way can POC glucose testing really function well in clinical practice. PMID- 26355759 TI - Cyclobutane Synthesis and Fragmentation. A Cascade Route to the Lycopodium Alkaloid (-)-Huperzine A. AB - An asymmetric total synthesis of the nootropic alkaloid (-)-huperzine A was completed using a cascade sequence initiated by an intramolecular aza-Prins reaction and terminated by a stereoelectronically guided fragmentation of a cyclobutylcarbinyl cation as the key step in assembling the bicyclo[3.3.1]nonene core of the natural product. Intramolecular [2 + 2]-photocycloaddition of the crotyl ether of (S)-4-hydroxycyclohex-2-enone afforded a bicyclo[4.2.0]octanone containing an embedded tetrahydrofuran in which the cyclohexanone moiety was converted to a triisopropylsilyl enol ether and functionalized as an allylic azide. The derived primary amine was acylated with alpha-phenylselenylacrylic acid, and the resulting amide was reacted with trimethylaluminum to give a [2 + 2]-cycloadduct, which underwent retroaldol fission to produce a fused alpha phenylselenyl delta-lactam. Periodate oxidation of this lactam led directly to an alpha-pyridone, which was converted to a fused 2-methoxypyridine. Reductive cleavage of the activated "pyridylic" C-O bond in this tetracycle and elaboration of the resultant hydroxy ketone to a diketone was followed by chemoselective conversion of the methyl ketone in this structure to an endo isopropenyl group. Condensation of the remaining ketone with methyl carbamate in the presence of acid initiated the programmed cascade sequence and furnished a known synthetic precursor to huperzine A. Subsequent demethylation of the carbamate and the methoxypyridine, accompanied by in situ decarboxylation of the intermediate carbamic acid, gave (-)-huperzine A. PMID- 26355760 TI - Pharmacogenetic-guided Warfarin Dosing Algorithm in African-Americans. AB - We aim to develop warfarin dosing algorithm for African-Americans. We explored demographic, clinical, and genetic data from a previously collected cohort of 163 African-American patients with a stable warfarin dose. We explored 2 approaches to develop the algorithm: multiple linear regression and artificial neural network (ANN). The clinical significance of the 2 dosing algorithms was evaluated by calculating the percentage of patients whose predicted dose of warfarin was within 20% of the actual dose. Linear regression model and ANN model predicted the ideal dose in 52% and 48% of the patients, respectively. The mean absolute error using linear regression model was estimated to be 10.8 mg compared with 10.9 mg using ANN. Linear regression and ANN models identified several predictors of warfarin dose including age, weight, CYP2C9 genotype *1/*1, VKORC1 genotype, rs12777823 genotype, rs2108622 genotype, congestive heart failure, and amiodarone use. In conclusion, we developed a warfarin dosing algorithm for African Americans. The proposed dosing algorithm has the potential to recommend warfarin doses that are close to the appropriate doses. The use of more sophisticated ANN approach did not result in improved predictive performance of the dosing algorithm except for patients of a dose of >=49 mg/wk. PMID- 26355761 TI - Homoplantaginin Inhibits Palmitic Acid-induced Endothelial Cells Inflammation by Suppressing TLR4 and NLRP3 Inflammasome. AB - Palmitic acid (PA)-induced vascular endothelial inflammation plays a pivotal role in the occurrence and development of vascular diseases. The present study was conducted to examine the effect of homoplantaginin, a main flavonoid from a traditional Chinese medicine Salvia plebeia R. Br., on PA-treated human umbilical vein endothelial cells inflammation and the underlying molecular mechanism. Firstly, we found that homoplantaginin (0.1, 1, 10 MUM) dose-dependently reduced expression of toll-like receptor-4 evoked by PA (100 MUM). The inhibitory effect of homoplantaginin was further confirmed under lipopolysaccharide challenge. In addition, downstream adapted proteins including myeloid differentiation primary response gene 88, toll/interleukin-1 receptor-domain containing adaptor-inducing interferon-beta and tumor necrosis factors receptor associated factor-6 were successfully inhibited by homoplantaginin under PA treatment. Also, we found that homoplantaginin tightly controlled PA-induced reactive oxygen species to prevent nucleotide-binding domain-like receptor 3 (NLRP3) inflammasome activation by suppressing reactive oxygen species-sensitive thioredoxin-interacting protein, NLRP3, and caspase-1. Meanwhile, protein and mRNA levels of inflammatory mediators (interleukin-1beta, intercellular cell adhesion molecule-1, and monocyte chemotactic protein-1) were decreased by homoplantaginin. Furthermore, homoplantaginin restored PA-impaired nitric oxide generation. Taken together, these results indicated that homoplantaginin protected endothelial cells from ameliorating PA-induced endothelial inflammation via suppressing toll-like receptor-4 and NLRP3 pathways, and restoring nitric oxide generation, suggesting it may be a potential candidate for further development in the prevention and treatment of vascular diseases. PMID- 26355762 TI - Pigmented perivascular epithelioid cell tumor of the skin: first case report. AB - The authors present a first case of pigmented perivascular epithelioid cell tumor (PEComa) of the skin, which was misdiagnosed histopathologically as metastatic melanoma. PEComa are exceedingly rare neoplasms, and only a few cases have been reported in kidney, liver, and pelvis. Herein, we describe this very rare entity in the subcutaneous tissue of the flank with very similar if not identical morphology of renal clear cell carcinoma. Because of the presence of focal melanin pigmentation and strong positivity for HMB-45, the lesion was mistaken for metastatic melanoma. To the best of authors' knowledge, this is the first case of cutaneous PEComa with melanin pigmentation. Awareness about occurrence of the lesion in the subcutaneous tissue and its unique immunoprofile would be helpful to reach correct diagnosis and to distinguish this lesion from melanoma or metastatic renal clear cell carcinoma. PMID- 26355763 TI - Follicular Induction Changes Overlying a Melanocytic Nevus. PMID- 26355764 TI - Myxoid Dermatofibrosarcoma Protuberans of the Vulva: Case Report of a Rare Variant in an Unusual Location, With Unusual Morphologic and Immunohistochemical Features. AB - Dermatofibrosarcoma protuberans (DFSP) is a low-to-intermediate grade infiltrative dermal neoplasm with a predilection for the trunk and extremities. DFSP in the vulvar region is extremely rare, with fewer than 50 cases reported to date in the literature. The histologic diagnosis of this neoplasm is facilitated by the characteristic storiform pattern of spindle cells with infiltration into the subcutaneous fat in a "honeycomb" pattern. However, morphologic variants including the very rare myxoid DFSP have been recognized that pose significant diagnostic difficulties, especially when they occur at unusual sites. The authors describe a case of myxoid DFSP of the vulva in a 44-year-old woman that was initially misdiagnosed as a neurofibroma. Subsequent excision led to significant challenges in diagnosis due to lack of typical morphology and unusual immunohistochemical staining pattern. Presence of peripheral adipose tissue trapping was noted focally that led to suspicion of DFSP. The diagnosis was confirmed by the detection of the characteristic COL1A1/PDGFB fusion transcript by reverse-transcription polymerase chain reaction. This case underscores the diagnostic challenge presented by variants of DFSP presenting in unusual locations and the value of molecular confirmation of the diagnosis. PMID- 26355765 TI - Efficacy and tolerability of vildagliptin as first line treatment in patients with diabetes type 2 in an outpatient setting. AB - BACKGROUND: Inhibitors of dipeptidyl-peptidase IV are recommended as second-line therapy in type 2 diabetes (DT2), but data, as a first-line treatment in everyday clinical practice are scarce. To address this issue we conducted a 12-month, clinical study in an outpatient setting, using vildagliptin as the first-line treatment. METHODS: Ninety-one drug naive patients with DT2 started with vildagliptin monotherapy (100 mg daily) for 4 months and were scheduled to regular 4-monthly visits for 1 year. Patients received add-on treatment with metformin or metformin and glimepiride according to their glycosylated hemoglobin (HbA1c) at each study-visit. RESULTS: HbA1c was significantly decreased with vildagliptin monotherapy from 8.16 % +/- 1.60 to 7.52 % +/- 1.60, p < 0.001. Only 39 % of the patients achieved the target of HbA1c <= 7.0 % at the end of the 4th month. Mean change in HbA1c was significantly correlated with baseline HbA1c values (r = -0.51, p < 0.001). At the end of the study only 35 % of the patients remained on vildagliptin monotherapy while the rest required add-on treatment with metformin or metformin and sulfonylurea. CONCLUSIONS: Vildagliptin is well tolerated either as monotherapy or in combination but the majority of patients require add-on therapy shortly after the beginning of treatment. PMID- 26355766 TI - Modulation of Bone-Specific Tissue Regeneration by Incorporating Bone Morphogenetic Protein and Controlling the Shell Thickness of Silk Fibroin/Chitosan/Nanohydroxyapatite Core-Shell Nanofibrous Membranes. AB - The presence of both osteoconductive and osteoinductive factors is important in promoting stem cell differentiation toward the osteogenic lineage. In this study, we prepared silk fibroin/chitosan/nanohydroxyapatite/bone morphogenetic protein-2 (SF/CS/nHAP/BMP-2, SCHB2) nanofibrous membranes (NFMs) by incorporating BMP-2 in the core and SF/CS/nHAP as the shell layer of a nanofiber with two different shell thicknesses (SCHB2-thick and SCHB-thin). The physicochemical properties of SCHB2 membranes were characterized and compared with those of SF/CS and SF/CS/nHAP NFMs. When tested in release studies, the release rate of BMP-2 and the concentration of BMP-2 in the release medium were higher for SCHB2-thin NFMs because of reduced shell thickness. The BMP-2 released from the nanofiber retained its osteoinductive activity toward human-bone-marrow-derived mesenchymal stem cells (hMSCs). Compared with SF/CS and SF/CS/nHAP NFMs, the incorporation of BMP-2-promoted osteogenic differentiation of hMSCs and the SCHB-thin NFM is the best scaffold during in vitro cell culture. Gene expression analysis by real-time quantitative polymerase chain reaction detected the evolution of both early and late marker genes of bone formation. The relative mRNA expression is in accordance with the effect of BMP-2 incorporation and shell thickness, while the same was reconfirmed through the quantification of bone marker protein osteocalcin. In vivo experiments were carried out by subcutaneously implanting hMSC-seeded SCHB2-thin NFMs and acellular controls on the back sides of nude mice. Immunohistochemical and histological staining confirmed ectopic bone formation and osteogenesis of hMSCs in SCHB2-thin NFMs. In conclusion, the SCHB2 thin NFM could be suggested as a promising scaffold for bone tissue engineering. PMID- 26355767 TI - Molecular Insight in Structure and Activity of Highly Efficient, Low-Ir Ir-Ni Oxide Catalysts for Electrochemical Water Splitting (OER). AB - Mixed bimetallic oxides offer great opportunities for a systematic tuning of electrocatalytic activity and stability. Here, we demonstrate the power of this strategy using well-defined thermally prepared Ir-Ni mixed oxide thin film catalysts for the electrochemical oxygen evolution reaction (OER) under highly corrosive conditions such as in acidic proton exchange membrane (PEM) electrolyzers and photoelectrochemical cells (PEC). Variation of the Ir to Ni ratio resulted in a volcano type OER activity curve with an unprecedented 20-fold improvement in Ir mass-based activity over pure Ir oxide. In situ spectroscopic probing of metal dissolution indicated that, against common views, activity and stability are not directly anticorrelated. To uncover activity and stability controlling parameters, the Ir-Ni mixed thin oxide film catalysts were characterized by a wide array of spectroscopic, microscopic, scattering, and electrochemical techniques in conjunction with DFT theoretical computations. By means of an intuitive model for the formation of the catalytically active state of the bimetallic Ir-Ni oxide surface, we identify the coverage of reactive surface hydroxyl groups as a suitable descriptor for the OER activity and relate it to controllable synthetic parameters. Overall, our study highlights a novel, highly active oxygen evolution catalyst; moreover, it provides novel important insights into the structure and performance of bimetallic oxide OER electrocatalysts in corrosive acidic environments. PMID- 26355768 TI - Preclinical pharmacokinetics, tissue distribution and excretion studies of a novel anti-candidal agent-thiosemicarbazide derivative of isoniazid (TSC-INH) by validated UPLC-MS/MS assay. AB - A simple and sensitive UPLC-MS/MS assay was developed and validated for rapid determination of thiosemicarbazide derivative of isoniazid (TSC-INH), a potent anti-candidal agent in rat plasma, tissues, urine and feces. All biological samples were prepared by protein precipitation method using celecoxib as an internal standard (IS). Chromatographic separation was achieved on Acquity BEHTM C18 (50*2.1 mm, 1.7 MUm) column using gradient mobile phase of acetonitrile and water (containing 0.1% formic acid) at flow rate of 0.3 mL/min. The MRM transitions were monitored at m/z 305.00->135.89 for TSC-INH and m/z 380.08 >316.03 for IS in ESI negative mode. All validation parameter results were within the acceptable range described in guideline for bioanalytical method validation. The pharmacokinetic study showed that the compound TSC-INH was orally active with 66% absolute bioavailability in rats. It was rapidly absorbed with peak plasma concentration of 1985.92 ng/mL achieved within 1 h after single oral dose (10 mg/kg) administration. TSC-INH exhibited rapid distribution across the body with highest levels in liver and lungs. Penetration in brain tissues suggests that TSC INH crossed the blood brain barrier. Only 5.23% of the orally administered drug was excreted as unconverted form in urine and feces implying that TSC-INH was metabolized extensively before excretion. With the preliminary knowledge of in vivo pharmacokinetics and disposition properties, this study will be beneficial for further development of compound TSC-INH in future studies. PMID- 26355770 TI - Monitoring utilizations of amino acids and vitamins in culture media and Chinese hamster ovary cells by liquid chromatography tandem mass spectrometry. AB - Monitoring amino acids and vitamins is important for understanding human health, food nutrition and the culture of mammalian cells used to produce therapeutic proteins in biotechnology. A method including ion pairing reversed-phase liquid chromatography with tandem mass spectrometry was developed and optimized to quantify 21 amino acids and 9 water-soluble vitamins in Chinese hamster ovary (CHO) cells and culture media. By optimizing the chromatographic separation, scan time, monitoring time window, and sample preparation procedure, and using isotopically labeled (13)C, (15)N and (2)H internal standards, low limits of quantitation (<=0.054 mg/L), good precision (<10%) and good accuracy (100+/-10%) were achieved for nearly all the 30 compounds. Applying this method to CHO cell extracts, statistically significant differences in the metabolite levels were measured between two cell lines originated from the same host, indicating differences in genetic makeup or metabolic activities and nutrient supply levels in the culture media. In a fed-batch process of manufacturing scale bioreactors, two distinguished trends for changes in amino acid concentrations were identified in response to feeding. Ten essential amino acids showed a zigzag pattern with maxima at the feeding days, and 9 non-essential amino acids displayed a smoothly changing profile as they were mainly products of cellular metabolism. Five of 9 vitamins accumulated continuously during the culture period, suggesting that they were fed in access. The method serves as an effective tool for the development and optimization of mammalian cell cultures. PMID- 26355769 TI - Methods for differential and quantitative analyses of brain neurosteroid levels by LC/MS/MS with ESI-enhancing and isotope-coded derivatization. AB - The analysis of changes in the brain neurosteroid (NS) levels due to various stimuli can contribute to the elucidation of their physiological roles, and the discovery and development of new antipsychotic agents targeting neurosteroidogenesis. We developed methods for the differential and quantitative analyses of the brain levels of allopregnanolene (AP) and its precursor, pregnenolone (PREG), using liquid chromatography/electrospray ionization-tandem mass spectrometry (LC/ESI-MS/MS) combined with derivatization using 2-hydrazino-1 methylpyridine (HMP) and its isotope-coded analogue, (2)H3-HMP (d-HMP). For the differential analysis, the brain sample of an untreated rat was derivatized with HMP, while the brain sample of a treated (stressed or drug-administered) rat was derivatized with d-HMP. The two derivatives were mixed and then subjected to LC/ESI-MS/MS. The stress- and drug (clozapine and fluoxetine)-evoked increases in the brain AP and PREG levels were accurately analyzed by the developed method. It was also possible to determine the absolute concentrations of the brain steroids when a deuterium-coded moiety was introduced to the standard steroids of known amounts by the derivatization and the resulting derivatives were used as internal standards. The HMP-derivatization enabled the highly sensitive detection and the use of d-HMP significantly improved the assay precision [the intra- (n=5) and inter-assay (n=5) relative standard deviations did not exceed 13.7%] and accuracy (analytical recovery ranged from 98.7 to 106.7%). PMID- 26355771 TI - Simultaneous determination of nintedanib and its metabolite by UPLC-MS/MS in rat plasma and its application to a pharmacokinetic study. AB - To establish a rapid and sensitive ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for the determination of concentration of nintedanib and its metabolite BIBF 1202 in rat plasma. The nintedanib and its metabolite and the internal standard (diazepam) were separated on an Acquity UPLC BEH C18 chromatography column (2.1 mm*50 mm, 1.7 MUm) using gradient elution with a mobile phase of acetonitrile and 0.1% formic acid in water at a flow rate of 0.30 mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) mode to monitor the precursor to-product ion transitions of m/z540.3->113.1 for nintedanib, m/z526.3->113.0 for BIBF 1202 and m/z285.3->193.1 for diazepam (IS) using a positive electrospray ionization interface. The method was validated for 1.0-200 ng/mL for nintedanib and 0.5-100 ng/mL for BIBF 1202 using 100 MUL of plasma sample. Total time for each chromatograph was 3.0 min. The intra- and inter-day precision and accuracy of the quality control samples at low, medium, and high concentration levels exhibited relative standard deviations (RSD) <10.8% and the accuracy values ranged from -11.9% to 10.4%. The method was successfully applied to a pharmacokinetic study of nintedanib and BIBF 1202 in rats after oral administration of nintedanib. PMID- 26355772 TI - A Platelet/CMC coupled with offline UPLC-QTOF-MS/MS for screening antiplatelet activity components from aqueous extract of Danshen. AB - Platelets play crucial roles in thromboembolic and cardiovascular disease. The main platelets membrane receptors include adenosine diphosphate receptors, thrombin receptors, thromboxane prostanoid receptors and collagen receptors. In this study, a Platelet/CMC coupled with offline UPLC-QTOF-MS/MS system was built to screen antiplatelet activity components from aqueous extract of Danshen, which serve as an agent of antiplatelet aggregation in Traditional Chinese Medicine. Rosmarinic acid, lithospermic acid, salvianolic acid B, two isomers of salvianolic acid B, salvianolic acid C, salvianolic acid D and salvianolic acid H/I were identified as the potential antiplatelet activity components. Moreover, rosmarinic acid, lithospermic acid, salvianolic acid B, salvianolic acid C and danshensu were tested in platelet aggregation in vitro assay. The results suggested their retention time was closely related to the antiplatelet aggregation activities. This study provides a rapid, effective and novel method for screening the potential antiplatelet activity components from Chinese herb medicines. PMID- 26355773 TI - Coupling treatment planning with navigation system: a new technological approach in treatment of head and neck tumors by electrochemotherapy. AB - BACKGROUND: Electrochemotherapy provides highly effective local treatment for a variety of tumors. In deep-seated tumors of the head and neck, due to complex anatomy of the region or inability to cover the whole tumor with standard electrodes, the use of long single needle electrodes is mandatory. In such cases, a treatment plan provides the information on the optimal configuration of the electrodes to adequately cover the tumor with electric field, while the accurate placement of the electrodes in the surgical room in patients can remain a problem. Therefore, during electrochemotherapy of two head and neck lymph-node metastases of squamous cell carcinoma origin, a navigation system for placement of electrodes was used. PATIENT AND METHODS: Electrochemotherapy of two lymph node metastases of cutaneous squamous cell carcinoma, one in the left parotid gland and the other in the neck just behind the left mandibular angle, was performed using intravenous administration of bleomycin and long single needle electrodes. The tumors were treated according to the prepared treatment plan, and executed with the use of navigation system. RESULTS: Coupling of treatment plan with the navigation system aided to an accurate placement of the electrodes. The navigation system helped the surgeon to identify the exact location of the tumors, and helped with the positioning of the long needle electrodes during their insertion, according to treatment plan. Five electrodes were inserted for each metastasis, one centrally in the tumor and four in the periphery of the tumor. Five weeks after electrochemotherapy, computed tomography images demonstrated partial response of the first metastasis and complete response of the second one. Six weeks after electrochemotherapy, fine-needle aspiration biopsy specimen obtained from the treated lesions revealed necrosis and inflammatory cells, without any viable tumor cells. CONCLUSION: We describe a new technological approach for electrochemotherapy of deep-seated head and neck tumors, coupling of the treatment planning with navigation system for accurate placement of the single long needle electrodes into and around the tumors, according to the treatment plan. Evidence of its effectiveness on two lymph-node metastases of cutaneous squamous cell carcinoma origin in neck lymph is provided. PMID- 26355774 TI - Development of Anilino-Maytansinoid ADCs that Efficiently Release Cytotoxic Metabolites in Cancer Cells and Induce High Levels of Bystander Killing. AB - Antibody anilino maytansinoid conjugates (AaMCs) have been prepared in which a maytansinoid bearing an aniline group was linked through the aniline amine to a dipeptide, which in turn was covalently attached to a desired monoclonal antibody. Several such conjugates were prepared utilizing different dipeptides in the linkage including Gly-Gly, l-Val-l-Cit, and all four stereoisomers of the Ala Ala dipeptide. The properties of AaMCs could be altered by the choice of dipeptide in the linker. Each of the AaMCs, except the AaMC bearing a d-Ala-d-Ala peptide linker, displayed more bystander killing in vitro than maytansinoid ADCs that utilize disulfide linkers. In mouse models, the anti-CanAg AaMC bearing a d Ala-l-Ala dipeptide in the linker was shown to be more efficacious against heterogeneous HT-29 xenografts than maytansinoid ADCs that utilize disulfide linkers, while both types of the conjugates displayed similar tolerabilities. PMID- 26355776 TI - Three-dimensional computed tomography of portopulmonary venous anastomoses in patients with esophageal varices before treatment. AB - AIM: Portopulmonary venous anastomoses (PPVA) are shunts between esophageal varices and pulmonary veins. Because PPVA can cause serious complications at the time of sclerotherapy for esophageal varices, it is essential to confirm the existence of any PPVA before treatment. METHODS: The study group comprised 101 patients in whom hemodynamics were evaluated on three-dimensional computed tomography (3D-CT) before either elective or prophylactic treatment of esophageal varices at Kitasato University East Hospital from October 2007 through August 2013. The presence or absence of PPVA, laboratory test results and 3D-CT findings were retrospectively examined in these patients. RESULTS: Nine patients had PPVA, and 92 patients did not. The underlying diseases in the PPVA group were: hepatitis C liver cirrhosis in three; non-B, non-C liver cirrhosis in three; non alcoholic steatohepatitis in one; primary biliary cirrhosis in one; and autoimmune hepatitis in one. The distribution of underlying diseases did not differ between the PPVA group and the non-PPVA group. When the study variables were statistically compared between the groups, the incidence of large, coil shaped esophageal varices (grade F3) differed significantly between the groups (P = 0.001). Multivariate analyses of factors related to PPVA revealed that only the grade F3 type of esophageal varices differed significantly between the groups (P = 0.005; hazard ratio, 5.21; 95% confidence interval, 3.1-16.4). CONCLUSION: In patients with grade F3 esophageal varices, the treatment method should be selected on the basis of an accurate hemodynamic analysis using 3D-CT before therapy. PMID- 26355777 TI - A Multi-Layered Screening Method to Identify Plant Regulatory Genes. AB - We used a seven-step process to identify genes involved in glucosinolate biosynthesis and metabolism in the Chinese cabbage (Brassica rapa). We constructed an annotated data set with 34,570 unigenes from B. rapa and predicted 11,526 glucosinolate-related candidate genes using expression profiles generated across nine stages of development on a 47k-gene microarray. Using our multi layered screening method, we screened 392 transcription factors, 843 pathway genes, and 4,162 ortholog genes associated with glucosinolate-related biosynthesis. Finally, we identified five genes by comparison of the pathway network genes including the transcription-factor genes and the ortholog-ontology genes. The five genes were anchored to the chromosomes of B. rapa to characterize their genetic-map positions, and phylogenetic reconstruction with homologous genes was performed. These anchored genes were verified by reverse-transcription polymerase chain reaction. While the five genes identified by our multi-layered screen require further characterization and validation, our study demonstrates the power of multi-layered screening after initial identification of genes on microarrays. PMID- 26355778 TI - An Algorithm for Constructing Principal Geodesics in Phylogenetic Treespace. AB - Most phylogenetic analyses result in a sample of trees, but summarizing and visualizing these samples can be challenging. Consensus trees often provide limited information about a sample, and so methods such as consensus networks, clustering and multidimensional scaling have been developed and applied to tree samples. This paper describes a stochastic algorithm for constructing a principal geodesic or line through treespace which is analogous to the first principal component in standard principal components analysis. A principal geodesic summarizes the most variable features of a sample of trees, in terms of both tree topology and branch lengths, and it can be visualized as an animation of smoothly changing trees. The algorithm performs a stochastic search through parameter space for a geodesic which minimizes the sum of squared projected distances of the data points. This procedure aims to identify the globally optimal principal geodesic, though convergence to locally optimal geodesics is possible. The methodology is illustrated by constructing principal geodesics for experimental and simulated data sets, demonstrating the insight into samples of trees that can be gained and how the method improves on a previously published approach. A java package called GeoPhytter for constructing and visualizing principal geodesics is freely available from www.ncl.ac.uk/ ntmwn/geophytter. PMID- 26355775 TI - Hepatocellular Carcinoma in Non-alcoholic Fatty Liver Disease: Epidemiology, Pathogenesis, and Prevention. AB - Hepatocellular cancer (HCC) is the fifth most prevalent cancer worldwide and the third leading cause of cancer-related deaths. Non-alcoholic fatty liver disease (NAFLD), a spectrum of hepatic disorders associated with obesity and the metabolic syndrome, is a recognized risk factor for HCC. NAFLD that is advanced to cirrhosis carries the highest risk for HCC, but there is increasing concern that NAFLD-associated HCC may also occur in non-cirrhotic liver. As NAFLD is rapidly becoming the most common liver condition, it has been implicated in the worrisome trend of rising HCC incidence in a number of countries, which may offset successful measures in reducing the effect of virus-related liver cancer. Independently or in synergy with cirrhosis, NAFLD may provide a special oncogenic microenvironment through its pathogenic association with chronic nutrient excess and adipose tissue remodeling, characterized by pro-inflammatory adipokine profiles, lipotoxicity, altered hepatocellular bioenergetics, and insulin resistance. Better understanding of this complex process, and development of reliable biomarkers for HCC will be critical for early recognition and risk prediction. Moreover, correcting deranged lipid metabolism and restoring insulin sensitivity by lifestyle measures and targeted pharmacotherapy holds major promise for effective prevention of NAFLD-associated HCC. PMID- 26355779 TI - An Odd Parity Checker Prototype Using DNAzyme Finite State Machine. AB - A finite-state machine (FSM) is an abstract mathematical model of computation used to design both computer programs and sequential logic circuits. Considered as an abstract model of computation, FSM is weak; it has less computational power than some other models of computation such as the Turing machine. This paper discusses the finite-state automata based on Deoxyribonucleic Acid (DNA) and different implementations of DNA FSMs. Moreover, a comparison was made to clarify the advantages and disadvantages of each kind of presented DNA FSMS. Since it is a major goal for nanoscince, nanotechnology and super molecular chemistry is to design synthetic molecular devices that are programmable and run autonomously. Programmable means that the behavior of the device can be modified without redesigning the whole structure. Autonomous means that it runs without externally mediated change to the work cycle. In this paper we present an odd Parity Checker Prototype Using DNAzyme FSM. Our paper makes use of a known design for a DNA nanorobotic device due to Reif and Sahu for executing FSM computations using DNAzymes. The main contribution of our paper is a description of how to program that device to do a FSM computation known as odd parity checking. We describe in detail finite state automaton built on 10-23 DNAzyme, and give its procedure of design and computation. The design procedure has two major phases: designing the language potential alphabet DNA strands, and depending on the first phase to design the DNAzyme possible transitions. PMID- 26355780 TI - Distance-Based Phylogenetic Methods Around a Polytomy. AB - Distance-based phylogenetic algorithms attempt to solve the NP-hard least-squares phylogeny problem by mapping an arbitrary dissimilarity map representing biological data to a tree metric. The set of all dissimilarity maps is a Euclidean space properly containing the space of all tree metrics as a polyhedral fan. Outputs of distance-based tree reconstruction algorithms such as UPGMA and neighbor-joining are points in the maximal cones in the fan. Tree metrics with polytomies lie at the intersections of maximal cones. A phylogenetic algorithm divides the space of all dissimilarity maps into regions based upon which combinatorial tree is reconstructed by the algorithm. Comparison of phylogenetic methods can be done by comparing the geometry of these regions. We use polyhedral geometry to compare the local nature of the subdivisions induced by least-squares phylogeny, UPGMA, and neighbor-joining when the true tree has a single polytomy with exactly four neighbors. Our results suggest that in some circumstances, UPGMA and neighbor-joining poorly match least-squares phylogeny. PMID- 26355781 TI - Hierarchical Probabilistic Interaction Modeling for Multiple Gene Expression Replicates. AB - Microarray technology allows for the collection of multiple replicates of gene expression time course data for hundreds of genes at a handful of time points. Developing hypotheses about a gene transcriptional network, based on time course gene expression data is an important and very challenging problem. In many situations there are similarities which suggest a hierarchical structure between the replicates. This paper develops posterior probabilities for network features based on multiple hierarchical replications. Through Bayesian inference, in conjunction with the Metropolis-Hastings algorithm and model averaging, a hierarchical multiple replicate algorithm is applied to seven sets of simulated data and to a set of Arabidopsis thaliana gene expression data. The models of the simulated data suggest high posterior probabilities for pairs of genes which have at least moderate signal partial correlation. For the Arabidopsis model, many of the highest posterior probability edges agree with the literature. PMID- 26355782 TI - Hybrid Ant Bee Algorithm for Fuzzy Expert System Based Sample Classification. AB - Accuracy maximization and complexity minimization are the two main goals of a fuzzy expert system based microarray data classification. Our previous Genetic Swarm Algorithm (GSA) approach has improved the classification accuracy of the fuzzy expert system at the cost of their interpretability. The if-then rules produced by the GSA are lengthy and complex which is difficult for the physician to understand. To address this interpretability-accuracy tradeoff, the rule set is represented using integer numbers and the task of rule generation is treated as a combinatorial optimization task. Ant colony optimization (ACO) with local and global pheromone updations are applied to find out the fuzzy partition based on the gene expression values for generating simpler rule set. In order to address the formless and continuous expression values of a gene, this paper employs artificial bee colony (ABC) algorithm to evolve the points of membership function. Mutual Information is used for idenfication of informative genes. The performance of the proposed hybrid Ant Bee Algorithm (ABA) is evaluated using six gene expression data sets. From the simulation study, it is found that the proposed approach generated an accurate fuzzy system with highly interpretable and compact rules for all the data sets when compared with other approaches. PMID- 26355783 TI - Improved Exact Enumerative Algorithms for the Planted (l, d)-Motif Search Problem. AB - In this paper efficient exact algorithms are proposed for the planted ( l, d) motif search problem. This problem is to find all motifs of length l that are planted in each input string with at most d mismatches. The "quorum" version of this problem is also treated in this paper to find motifs planted not in all input strings but in at least q input strings. The proposed algorithms are based on the previous algorithms called qPMSPruneI and qPMS7 that traverse a search tree starting from a l-length substring of an input string. To improve these previous algorithms, several techniques are introduced, which contribute to reducing the computation time for the traversal. In computational experiments, it will be shown that the proposed algorithms outperform the previous algorithms. PMID- 26355784 TI - Indexing Graphs for Path Queries with Applications in Genome Research. AB - We propose a generic approach to replace the canonical sequence representation of genomes with graph representations, and study several applications of such extensions. We extend the Burrows-Wheeler transform (BWT) of strings to acyclic directed labeled graphs, to support path queries as an extension to substring searching. We develop, apply, and tailor this technique to a) read alignment on an extended BWT index of a graph representing pan-genome, i.e., reference genome and known variants of it; and b) split-read alignment on an extended BWT index of a splicing graph. Other possible applications include probe/primer design, alignments to assembly graphs, and alignments to phylogenetic tree of partial order graphs. We report several experiments on the feasibility and applicability of the approach. Especially on highly-polymorphic genome regions our pan-genome index is making a significant improvement in alignment accuracy. PMID- 26355785 TI - Merging Partially Labelled Trees: Hardness and a Declarative Programming Solution. AB - Intraspecific studies often make use of haplotype networks instead of gene genealogies to represent the evolution of a set of genes. Cassens et al. proposed one such network reconstruction method, based on the global maximum parsimony principle, which was later recast by the first author of the present work as the problem of finding a minimum common supergraph of a set of t partially labelled trees. Although algorithms have been proposed for solving that problem on two graphs, the complexity of the general problem on trees remains unknown. In this paper, we show that the corresponding decision problem is NP-complete for t=3. We then propose a declarative programming approach to solving the problem to optimality in practice, as well as a heuristic approach, both based on the idpsystem, and assess the performance of both methods on randomly generated data. PMID- 26355786 TI - Optimizing Spaced k-mer Neighbors for Efficient Filtration in Protein Similarity Search. AB - Large-scale comparison or similarity search of genomic DNA and protein sequence is of fundamental importance in modern molecular biology. To perform DNA and protein sequence similarity search efficiently, seeding (or filtration) method has been widely used where only sequences sharing a common pattern or "seed" are subject to detailed comparison. Therefore these methods trade search sensitivity with search speed. In this paper, we introduce a new seeding method, called spaced k-mer neighbors, which provides a better tradeoff between the sensitivity and speed in protein sequence similarity search. With the method of spaced k-mer neighbors, for each spaced k-mer, a set of spaced k-mers is selected as its neighbors. These pre-selected spaced k-mer neighbors are then used to detect hits between query sequence and database sequences. We propose an efficient heuristic algorithm for the spaced neighbor selection. Our computational experimental results demonstrate that the method of spaced k-mer neighbors can improve the overall tradeoff efficiency over existing seeding methods. PMID- 26355787 TI - Predicting Essential Proteins Based on Weighted Degree Centrality. AB - Essential proteins are vital for an organism's viability under a variety of conditions. There are many experimental and computational methods developed to identify essential proteins. Computational prediction of essential proteins based on the global protein-protein interaction (PPI) network is severely restricted because of the insufficiency of the PPI data, but fortunately the gene expression profiles help to make up the deficiency. In this work, Pearson correlation coefficient (PCC) is used to bridge the gap between PPI and gene expression data. Based on PCC and edge clustering coefficient (ECC), a new centrality measure, i.e., the weighted degree centrality (WDC), is developed to achieve the reliable prediction of essential proteins. WDC is employed to identify essential proteins in the yeast PPI and e-Coli networks in order to estimate its performance. For comparison, other prediction technologies are also performed to identify essential proteins. Some evaluation methods are used to analyze the results from various prediction approaches. The prediction results and comparative analyses are shown in the paper. Furthermore, the parameter lambda in the method WDC will be analyzed in detail and an optimal lambda value will be found. Based on the optimal lambda value, the differentiation of WDC and another prediction method PeC is discussed. The analyses prove that WDC outperforms other methods including DC, BC, CC, SC, EC, IC, NC, and PeC. At the same time, the analyses also mean that it is an effective way to predict essential proteins by means of integrating different data sources. PMID- 26355788 TI - Solving the Secondary Structure Matching Problem in Cryo-EM De Novo Modeling Using a Constrained K-Shortest Path Graph Algorithm. AB - Electron cryomicroscopy is becoming a major experimental technique in solving the structures of large molecular assemblies. More and more three-dimensional images have been obtained at the medium resolutions between 5 and 10 A. At this resolution range, major alpha-helices can be detected as cylindrical sticks and beta-sheets can be detected as plain-like regions. A critical question in de novo modeling from cryo-EM images is to determine the match between the detected secondary structures from the image and those on the protein sequence. We formulate this matching problem into a constrained graph problem and present an O(Delta(2)N(2)2(N)) algorithm to this NP-Hard problem. The algorithm incorporates the dynamic programming approach into a constrained K-shortest path algorithm. Our method, DP-TOSS, has been tested using alpha-proteins with maximum 33 helices and alpha-beta proteins up to five helices and 12 beta-strands. The correct match was ranked within the top 35 for 19 of the 20 alpha-proteins and all nine alpha beta proteins tested. The results demonstrate that DP-TOSS improves accuracy, time and memory space in deriving the topologies of the secondary structure elements for proteins with a large number of secondary structures and a complex skeleton. PMID- 26355789 TI - Systematic Approach to Computational Design of Gene Regulatory Networks with Information Processing Capabilities. AB - We present several measures that can be used in de novo computational design of biological systems with information processing capabilities. Their main purpose is to objectively evaluate the behavior and identify the biological information processing structures with the best dynamical properties. They can be used to define constraints that allow one to simplify the design of more complex biological systems. These measures can be applied to existent computational design approaches in synthetic biology, i.e., rational and automatic design approaches. We demonstrate their use on a) the computational models of several basic information processing structures implemented with gene regulatory networks and b) on a modular design of a synchronous toggle switch. PMID- 26355790 TI - Thermodynamic Post-Processing versus GC-Content Pre-Processing for DNA Codes Satisfying the Hamming Distance and Reverse-Complement Constraints. AB - Stochastic, meta-heuristic and linear construction algorithms for the design of DNA strands satisfying Hamming distance and reverse-complement constraints often use a GC-content constraint to pre-process the DNA strands. Since GC-content is a poor predictor of DNA strand hybridization strength the strands can be filtered by post-processing using thermodynamic calculations. An alternative approach is considered here, where the algorithms are modified to remove consideration of GC content and rely on post-processing alone to obtain large sets of DNA strands with satisfactory melting temperatures. The two approaches (pre-processing GC content and post-processing melting temperatures) are compared and are shown to be complementary when large DNA sets are desired. In particular, the second approach can give significant improvements when linear constructions are used. PMID- 26355791 TI - The temporal profile of retinal cell genesis in the marmoset monkey. AB - The New World marmoset monkey (Callithrix jacchus) has a relatively short gestational period compared with other primates but possesses a retina at a similar stage of maturation by birth. Previous studies have highlighted that the complex fovea of the marmoset undergoes a more rapid postnatal development in comparison with the Macaca monkey, reaching a mature stage earlier than these species. In this current study, we examined the prenatal proliferation profile of cells in the entire retina employing the thymidine analogs and also determined their phenotype by double-label immunocytochemistry using type-specific markers. Akin to other primate species, we demonstrate a centroperipheral gradient in the emergence of both neurons and Muller glia with cones, ganglion cells, and horizontal cells generated first in the fovea at fetal day (Fd)70-74 and with the last generated at the retinal edge at Fd115. Rods, bipolar cells, amacrine cells, displaced amacrine cells, and Muller glia were generated between Fd76 and Fd135 along the same gradient. Similar to foveal development, marmoset neuronal generation was rapid, only taking 51% of gestation whereas in Macaca this takes 81%. PMID- 26355792 TI - Base of Tongue Mass. Mucoepidermoid carcinoma. PMID- 26355793 TI - Rejoinder to "Reader reaction: A note on the evaluation of group testing algorithms in the presence of misclassification". PMID- 26355794 TI - Polyphenol intake is associated with low-grade inflammation, using a novel data analysis from the Moli-sani study. AB - The association of polyphenol content of human diet with low-grade inflammation is not yet fully understood. It was the objective of this study to evaluate the association of flavonoid and lignan intake with frequently used and easily applicable in clinical practice low-grade inflammation biomarkers, in a novel holistic approach. A total of 5,948 women and 5,965 men (aged >= 35 years) were analysed from the Moli-sani cohort, randomly recruited from the general population. The EPIC-FFQ was used for dietary assessment. Flavonol, flavone, flavanone, flavanol, anthocyanin, isoflavone and lignan intakes were calculated using Eurofir eBASIS and the polyphenol antioxidant content (PAC)-score was constructed to assess the total content of diet in these nutrients. CRP levels, WBC and PLT count and granulocyte to lymphocyte ratio were conceived as low-grade inflammation biomarkers. INFLA-score was constructed summarizing synergistic effects of these biomarkers. The INFLA-score was negatively associated with PAC score in different levels of adjustment, in both genders (for all beta-coef<0, P<0.05). 10 units increase in PAC-score was associated with 5-8% decrease in the likelihood of higher low-grade inflammation status (i.e. higher quartile of INFLA score) in men and women (odds ratio [ORs] 0.92 to 0.95, p<0.05). The total variation of INFLA-score that was explained by PAC-score was estimated to be 16.7% in women and 9.1% in men (%R2=16.7 and 9.1). In conclusion, polyphenol content of diet evaluated in a holistic approach was negatively associated with a score of low-grade inflammation biomarkers in a large population based study. For the first time low-grade inflammation was evaluated in a holistic way through INFLA-score and was associated with polyphenol content of diet. PMID- 26355795 TI - In situ Formation of a Monodispersed Spherical Mesoporous Nanosilica-Torlon Hollow-Fiber Composite for Carbon Dioxide Capture. AB - We describe a new template-free method for the in situ formation of a monodispersed spherical mesoporous nanosilica-Torlon hollow-fiber composite. A thin layer of Torlon hollow fiber that comprises silica nanoparticles was created by the in situ extrusion of a tetraethyl orthosilicate/N-methyl-2-pyrrolidone solution in a sheath layer and a Torlon polymer dope in a core support layer. This new method can be integrated easily into current hollow-fiber composite fabrication processes. The hollow-fiber composites were then functionalized with 3-aminopropyltrimethoxy silane (APS) and evaluated for their CO2 -capture performance. The resulting APS-functionalized mesoporous silica nanoparticles/Torlon hollow fibers exhibited a high CO2 equilibrium capacity of 1.5 and 1.9 mmol g(-1) at 35 and 60 degrees C, respectively, which is significantly higher than values for fiber sorbents without nanoparticles reported previously. PMID- 26355796 TI - Meta-analysis at middle age: a personal history. AB - The 40-year history of meta-analysis is traced from the vantage point of one of its originators. Research syntheses leading to the first examples of meta analysis are identified. Early meta-analyses of the literature on psychotherapy outcomes and school class size are recounted. The influence on the development of meta-analysis of several statisticians and psychologists is described. Finally, some directions for future development of research synthesis methods are suggested. PMID- 26355797 TI - Reflections on the origins of meta-analysis. AB - In this interview, we discuss my early uses of meta-analytic procedures, first to combine p-values and then to combine effect sizes as well. My interest in quantifying the magnitude and the statistical significance of the effect of interpersonal expectations probably grew out of the following: (1) a long-held interest in the concept of replication and (2) a series of controversies over the very existence of any effect of interpersonal expectations held, for example, by psychological experimenters, classroom teachers, and leaders of various organizations. PMID- 26355799 TI - Message from Scientific Chairpersons. PMID- 26355798 TI - Some reflections on the evolution of meta-analysis. AB - I reflect on the evolution of meta-analysis in clinical research over 35 years since I first encountered the key ideas in the late 1970s. PMID- 26355800 TI - Scientific Committee. PMID- 26355801 TI - 9th International Congress of the International Society for Hemodialysis: Global Challenges in Hemodialysis. PMID- 26355802 TI - Chromosome aberrations detected by conventional karyotyping using novel mitogens in chronic lymphocytic leukemia: Clinical and biologic correlations. AB - To clarify whether karyotype aberrations (KA) involving regions not covered by the standard fluorescence in situ hybridization (FISH) panel have independent prognostic relevance, we evaluated KA by conventional cytogenetics in a learning cohort (LC; n = 166) and a validation cohort (VC; n = 250) of untreated chronic lymphocytic leukemia (CLL) patients. In the VC, novel mitogens were used to improve metaphase generation and TP53, NOTCH1, and SF3B1 mutations were assessed. KA undetected by FISH were found in 35 and 35% of the cases in the LC and VC, respectively. In addition to FISH, KA allowed reclassification of 23 and 26% of cases in the LC and VC, respectively, into a higher cytogenetic risk group. By multivariate analysis, both in the LC and VC, KA other than isolated 13q deletion correlated with a shorter time to first treatment (TFT; P < 0.001 and 0.003, respectively), while a complex karyotype predicted a worse overall survival (OS, P = 0.015 and 0.010, respectively). In the VC, where a comprehensive biologic assessment was performed, a shorter TFT was also predicted by stage (P < 0.001), IGHV mutational status (P = 0.05), and del(17p)/TP53 mutations (P = 0.033) while stage (P = 0.023) and del(17p)/TP53 mutations (P = 0.024) independently predicted a shorter OS. FISH results did not independently impact on TFT and OS, in the LC and VC cohorts; this was also the case for NOTCH1 and SF3B1 mutations in the VC. We suggest that in CLL, conventional karyotyping with novel mitogens could be more effective than FISH for the detection of KA allowing for a more precise refinement of prognosis. PMID- 26355803 TI - Pharmacokinetic and nephroprotective benefits of using Schisandra chinensis extracts in a cyclosporine A-based immune-suppressive regime. AB - Cyclosporine A (CsA) is a powerful immunosuppressive drug. However, nephrotoxicity resulting from its long-term usage has hampered its prolonged therapeutic usage. Schisandra chinensis extracts (SCE) have previously been used in traditional Chinese medicine and more recently coadministered with Western medicine for the treatment of CsA-induced side effects in the People's Republic of China. This study aimed to investigate the possible effects of SCE on the pharmacokinetics of CsA in rats and elucidate the potential mechanisms by which it hinders the development of CsA-induced nephrotoxicity. A liquid chromatography/tandem mass spectrometry method was developed and validated for determining the effect of SCE on the pharmacokinetics of CsA. Male Sprague Dawley rats, which were administered with CsA (25 mg/kg/d) alone or in combination with SCE (54 mg/kg/d and 108 mg/kg/d) for 28 days, were used to evaluate the nephroprotective effects of SCE. Our study showed that SCE increased the mean blood concentration of CsA. Furthermore, we found that the concomitant administration of SCE alongside CsA prevented the disruption of catalase activity and reduction in creatinine, urea, renal malondialdehyde, and glutathione peroxidase levels that would have otherwise occurred in the absence of SCE administration. SCE treatment markedly suppressed the expression of 4 hydroxynonenal, Bcl-2-associated X protein, cleaved caspase 3, and autophagy related protein LC3 A/B. On the other hand, the expression of heme oxygenase-1, nuclear factor erythroid 2-related factor 2 (Nrf2), and P-glycoprotein was enhanced by the very same addition of SCE. SCE was also able to increase the systemic exposure of CsA in rats. The renoprotective effects of SCE were thought to be mediated by its antiapoptotic and antioxidant abilities, which caused the attenuation of CsA-induced autophagic cell death. All in all, these findings suggest the prospective use of SCE as an effective adjunct in a CsA-based immunosuppressive regimen. PMID- 26355804 TI - Development of electron spin echo envelope modulation spectroscopy to probe the secondary structure of recombinant membrane proteins in a lipid bilayer. AB - Membrane proteins conduct many important biological functions essential to the survival of organisms. However, due to their inherent hydrophobic nature, it is very difficult to obtain structural information on membrane-bound proteins using traditional biophysical techniques. We are developing a new approach to probe the secondary structure of membrane proteins using the pulsed EPR technique of Electron Spin Echo Envelope Modulation (ESEEM) Spectroscopy. This method has been successfully applied to model peptides made synthetically. However, in order for this ESEEM technique to be widely applicable to larger membrane protein systems with no size limitations, protein samples with deuterated residues need to be prepared via protein expression methods. For the first time, this study shows that the ESEEM approach can be used to probe the local secondary structure of a (2) H-labeled d8 -Val overexpressed membrane protein in a membrane mimetic environment. The membrane-bound human KCNE1 protein was used with a known solution NMR structure to demonstrate the applicability of this methodology. Three different alpha-helical regions of KCNE1 were probed: the extracellular domain (Val21), transmembrane domain (Val50), and cytoplasmic domain (Val95). These results indicated alpha-helical structures in all three segments, consistent with the micelle structure of KCNE1. Furthermore, KCNE1 was incorporated into a lipid bilayer and the secondary structure of the transmembrane domain (Val50) was shown to be alpha-helical in a more native-like environment. This study extends the application of this ESEEM approach to much larger membrane protein systems that are difficult to study with X-ray crystallography and/or NMR spectroscopy. PMID- 26355805 TI - Review of the cost of venous thromboembolism. AB - BACKGROUND: Venous thromboembolism (VTE) is the second most common medical complication and a cause of excess length of hospital stay. Its incidence and economic burden are expected to increase as the population ages. We reviewed the recent literature to provide updated cost estimates on VTE management. METHODS: Literature search strategies were performed in PubMed, Embase, Cochrane Collaboration, Health Economic Evaluations Database, EconLit, and International Pharmaceutical Abstracts from 2003-2014. Additional studies were identified through searching bibliographies of related publications. RESULTS: Eighteen studies were identified and are summarized in this review; of these, 13 reported data from the USA, four from Europe, and one from Canada. Three main cost estimations were identified: cost per VTE hospitalization or per VTE readmission; cost for VTE management, usually reported annually or during a specific period; and annual all-cause costs in patients with VTE, which included the treatment of complications and comorbidities. Cost estimates per VTE hospitalization were generally similar across the US studies, with a trend toward an increase over time. Cost per pulmonary embolism hospitalization increased from $5,198-$6,928 in 2000 to $8,764 in 2010. Readmission for recurrent VTE was generally more costly than the initial index event admission. Annual health plan payments for services related to VTE also increased from $10,804-$16,644 during the 1998-2004 period to an estimated average of $15,123 for a VTE event from 2008 to 2011. Lower costs for VTE hospitalizations and annualized all-cause costs were estimated in European countries and Canada. CONCLUSION: Costs for VTE treatment are considerable and increasing faster than general inflation for medical care services, with hospitalization costs being the primary cost driver. Readmissions for VTE are generally more costly than the initial VTE admission. Further studies evaluating the economic impact of new treatment options such as the non-vitamin K antagonist oral anticoagulants on VTE treatment are warranted. PMID- 26355806 TI - Body size across the life course and prostate cancer in the Health Professionals Follow-up Study. AB - Current evidence of an association between body size and prostate cancer is conflicting, possibly due to differential effects of body size across the lifespan and the heterogeneity of the disease. We therefore examined childhood and adult body size in relation to total incident prostate cancer and prognostic subtypes in a prospective cohort of 47,491 US men in the Health Professionals Follow-up Study. We assessed adult height, body mass index (BMI) in early and middle-to-late adulthood, adult waist circumference, and body shape at age 10. With follow-up from 1986 to 2010, we estimated the relative risk (RR) of prostate cancer using Cox proportional hazards models. We identified 6,183 incident cases. Tallness was associated with increased risk of advanced-stage tumors, particularly fatal disease (RR = 1.66, 95% CI 1.23-2.23, highest vs. lowest quintile, ptrend < 0.001). High BMI at age 21 was inversely associated with total prostate cancer (RR = 0.89, 95% CI 0.80-0.98, BMI >= 26 vs. 20-21.9, ptrend = 0.01) and with fatal and advanced disease. The association for late adult BMI differed by age (pinteraction < 0.001); high BMI was inversely associated with total prostate cancer (RR = 0.64, 95% CI 0.51-0.78, BMI >= 30 vs. 21-22.9, ptrend <0.001) and with non-advanced and less aggressive tumors among men <= 65 years, whereas no association was seen among men >65 years. Adult waist circumference was weakly inversely associated with less aggressive disease. Childhood obesity was unclearly related to risk. Our study confirms tall men to be at increased risk of fatal and advanced prostate cancer. The influence of adiposity varies by prognostic disease subtype and by age. The relationship between body size and prostate cancer is complex. Body size changes progressively throughout life and consequent effects on prostate cancer risk may be associated with related changes in hormonal and metabolic pathways. This large prospective study examined potential associations between the risk of various prostate cancer subtypes and multiple anthropometric measures at different ages in men. Tallness was confirmed to be associated with an elevated risk of advanced prostate cancer, particularly fatal disease. The extent to which body weight influenced risk varied according to factors such as age and disease subtype. PMID- 26355807 TI - Comparative effects of more versus less aggressive treatment with statins on the long-term outcome of patients with acute ischemic stroke. AB - BACKGROUND AND AIMS: There are no studies that compared the effects of different intensities of statin treatment on the long-term outcome of patients with recent ischemic stroke. We aimed to evaluate these effects. METHODS: We prospectively studied 436 consecutive patients who were discharged after acute ischemic stroke (39.2% males, age 78.6 +/- 6.7 years). Statin treatment was categorized in equipotent doses of atorvastatin. One year after discharge, the functional status was assessed with the modified Rankin scale (mRS). Adverse outcome was defined as mRS between 2 and 6. The occurrence of ischemic stroke, myocardial infarction and death was recorded. RESULT: Adverse outcome rates were lower in patients treated with atorvastatin 20 mg/day or more potent doses of statins than in patients treated with atorvastatin 10 mg/day (63.5, 38.2 and 48.2%, respectively; p = 0.004). In binary logistic regression analysis, independent predictors of adverse outcome were the mRS at discharge (relative risk (RR) 2.33, 95% confidence interval (CI) 1.77-3.07, p < 0.001) whereas more aggressive treatment with statins independently predicted favorable outcome (atorvastatin 20 vs. 10 mg/day, RR 0.30, 95% CI 0.11-0.87, p = 0.026; atorvastatin 40 mg/day or more potent dose of statins vs. atorvastatin 10 mg/day, RR 1.66, 95% CI 0.62-4.44, p = NS). The incidence of cardiovascular events and all-cause mortality showed a trend for being lower in patients treated with atorvastatin 40-80 mg/day or rosuvastatin 10 40 mg/day than in those treated with less potent doses of statins. CONCLUSION: More aggressive statin treatment improves the long-term functional outcome of patients with acute ischemic stroke more than less aggressive treatment. PMID- 26355808 TI - Fusion after intradural spine tumor resection in adults: A review of evidence and practices. AB - There is ample evidence supporting concomitant fusion after intradural spinal tumor resection in select pediatric patients. Unfortunately, the data are scarcer in adults. The objective of this work is to review the published literature and analyze practice patterns for stabilization and fusion after intradural tumor resection in adults. We performed a literature review via PubMed for information available regarding fusion in adults with intradural spine tumors. Additionally, we manually searched the references of selected articles to add relevant articles. Finally, we retrieved the criteria for fusion (if any) in the selected studies. A total of 639 articles were found and 35 were finally selected for analysis. Of those, three were literature reviews and 32 were retrospective case series. There were a total of 1288 patients on the series with 104 of them requiring fusion (8.1%). The median follow up of all the series was 24 months (range 1.5-180).The criteria for fusion that were common in most cases series were: previous deformity (i.e. kyphosis in the cervical spine), 3 or more levels of laminectomy, laminectomy encompassing a spinal junction, "young adults" (33 +/ 4.2 years), facetectomy >= 50% (unilateral or bilateral), persistence of deformity after 1 year of the surgery and, C2 laminectomy. There appears to be some consistent practices for fusion after intradural tumor resection in adults, but this is based on retrospective analyses of case series. Prospective or randomized trials will likely provide more evidence based support for this practice. PMID- 26355809 TI - Transient isolated ocular motor abnormality related to perilesional edema of an acute medullary microbleed: A case report and review of the literatures. AB - We report a case of transient isolated gaze-evoked nystagmus with ocular lateropulsion in a patient with an acute medullary microbleed which was detected by brain magnetic resonance imaging. Considering the correlation between the neural structures involved by the lesion and the ocular motor symptoms of this patient, we suggest that the perilesional edema of the acute medullary microbleed is responsible for this transient ocular motor abnormality. PMID- 26355810 TI - Association of early inflammatory parameters after subarachnoid hemorrhage with functional outcome: A prospective cohort study. AB - OBJECTIVE: Early brain injury after aneurysmal subarachnoid hemorrhage (aSAH) comprises a pronounced neuroinflammatory reaction. Nevertheless, its relevance for functional outcome and its role as outcome predictor remains uncertain. We evaluated the relationship of various early inflammatory parameters regarding functional outcome according to the modified Rankin Scale score (mRS) at discharge (primary objective) and six months after aSAH. PATIENTS: A total of 81 patients (63% female) with a mean age of 53.8 +/- 13.2 years were included. METHODS: At admission clinical data and various inflammatory parameters in serum and - wherever applicable - cerebrospinal fluid (CSF) of patients after aSAH were assessed. Outcome was evaluated according to dichotomized mRS at discharge and six months after aSAH (unfavorable outcome: mRS 3-6). Univariate and thereafter multivariate logistic regression analyses were performed using SAS 9.2. RESULTS: Elevated levels of interleukin 6 (IL-6) and leukemia inhibitory factor (LIF) in serum and CSF were related to unfavorable outcome at discharge (p<0.05; univariate analyses). IL-6 remains the only parameter relevant for outcome applying a multivariate model including the relevant baseline characteristics. Six months after aSAH no significant correlation was found regarding the outcome, most likely due to the high drop-out rate (27%). A pronounced rise of LIF serum and CSF levels after aSAH was observed. CONCLUSION: Higher early IL-6 serum levels after aSAH are associated with poor outcome at discharge. In addition, involvement of LIF in the early inflammatory reaction after aSAH has been demonstrated. PMID- 26355811 TI - Adsorption and desorption of DNA tuned by hydroxyl groups in graphite oxides based solid extraction material. AB - The extraction of DNA is the most crucial method used in molecular biology. Up to date silica matrices has been widely applied as solid support for selective DNA adsorption and extraction. However, since adsorption force of SiOH functional groups is much greater than that of desorption force, the DNA extraction efficiency of silica surfaces is limited. In order to increase the DNA extraction yield, a new surface with different functional groups which possess of greater desorption property is required. In this study, we proposed cellulose/graphite oxide (GO) composite as an alternative material for DNA adsorption and extraction. GO/Cellulose composite provides the major adsorption and desorption of DNA by COH, which belongs to alkyl or phenol type of OH functional group. Compared to SiOH, COH is less polarized and reactive, therefore the composite might provide a higher desorption of DNA during the elution process. The GO/cellulose composite were prepared in spherical structure by mixing urea, cellulose, NaOH, Graphite oxide and water. The concentration of GO within the composites were controlled to be 0-4.15 wt.%. The extraction yield of DNA increased with increasing weight percentage of GO. The highest yield was achieved at 4.15 wt.% GO, where the extraction efficiency was reported as 660.4 ng/MUl when applying 2M GuHCl as the binding buffer. The absorbance ratios between 260 nm and 280 nm (A260/A280) of the DNA elution was demonstrated as 1.86, indicating the extracted DNA consisted of high purity. The results proved that GO/cellulose composite provides a simple method for selective DNA extraction with high extraction efficiency of pure DNA. PMID- 26355812 TI - Piezoelectric polymers as biomaterials for tissue engineering applications. AB - Tissue engineering often rely on scaffolds for supporting cell differentiation and growth. Novel paradigms for tissue engineering include the need of active or smart scaffolds in order to properly regenerate specific tissues. In particular, as electrical and electromechanical clues are among the most relevant ones in determining tissue functionality in tissues such as muscle and bone, among others, electroactive materials and, in particular, piezoelectric ones, show strong potential for novel tissue engineering strategies, in particular taking also into account the existence of these phenomena within some specific tissues, indicating their requirement also during tissue regeneration. This referee reports on piezoelectric materials used for tissue engineering applications. The most used materials for tissue engineering strategies are reported together with the main achievements, challenges and future needs for research and actual therapies. This review provides thus a compilation of the most relevant results and strategies and a start point for novel research pathways in the most relevant and challenging open questions. PMID- 26355813 TI - Heterogeneous photo-Fenton reaction on hematite (alpha-Fe2O3){104}, {113} and {001} surface facets. AB - The exposed surface facets play an important role in determining the catalytic performance of nanostructured materials. In this study, we report the synthesis of hematite nanoparticles with three varying morphologies with exposure of well controlled {104}, {113} and {001} surfaces. The better shape control of hematite particles has provided a direct correlation between the surface facets and the photocatalytic performance. The catalytic photodegradation of MB using hematite nanoparticles reveals that the reaction follows the heterogeneous photo-Fenton process under visible light irradiation. The catalytic performance of hematite surface facets follows the order of {113} > {104} > {001}. Density functional theory (DFT) calculations were conducted to demonstrate the atomic surface structures and the corresponding charge distribution. The results indicate that the catalytic activity depends on surface atom arrangements as well as the number and the type of surface terminated hydroxyl groups bonding to underlying Fe atoms, where low valence states of Fe on {104} and {113} planes have the highest probability to be oxidized by H2O2 and the concurrently generated Fe((3+x)+) sites are more electronegative to accept electrons from activated dye molecules. The findings are of fundamental importance to understand the surface-dependence of photocatalytic properties, thus shedding new light on the catalytic application of hematite particles. PMID- 26355815 TI - Hippocampal closed-loop modeling and implications for seizure stimulation design. AB - OBJECTIVE: Traditional hippocampal modeling has focused on the series of feedforward synapses known as the trisynaptic pathway. However, feedback connections from CA1 back to the hippocampus through the entorhinal cortex (EC) actually make the hippocampus a closed-loop system. By constructing a functional closed-loop model of the hippocampus, one may learn how both physiological and epileptic oscillations emerge and design efficient neurostimulation patterns to abate such oscillations. APPROACH: Point process input-output models where estimated from recorded rodent hippocampal data to describe the nonlinear dynamical transformation from CA3 -> CA1, via the schaffer-collateral synapse, and CA1 -> CA3 via the EC. Each Volterra-like subsystem was composed of linear dynamics (principal dynamic modes) followed by static nonlinearities. The two subsystems were then wired together to produce the full closed-loop model of the hippocampus. MAIN RESULTS: Closed-loop connectivity was found to be necessary for the emergence of theta resonances as seen in recorded data, thus validating the model. The model was then used to identify frequency parameters for the design of neurostimulation patterns to abate seizures. SIGNIFICANCE: Deep-brain stimulation (DBS) is a new and promising therapy for intractable seizures. Currently, there is no efficient way to determine optimal frequency parameters for DBS, or even whether periodic or broadband stimuli are optimal. Data-based computational models have the potential to be used as a testbed for designing optimal DBS patterns for individual patients. However, in order for these models to be successful they must incorporate the complex closed-loop structure of the seizure focus. This study serves as a proof-of-concept of using such models to design efficient personalized DBS patterns for epilepsy. PMID- 26355816 TI - Health-related quality of life and health condition of community-dwelling populations with cancer, stroke, and cardiovascular disease. AB - [Purpose] The purpose of this study was to investigate health conditions and HRQoL (health-related quality of life) of community-dwelling populations with cancer, stroke, and CVD (cardiovascular disease) based on standardized data. [Subjects] The study subjects numbered 422 in total: 179 patients had cancer, 128 were stroke patients, and 115 were CVD patients. [Methods] This study used data collected during health interviews carried out as part of the sixth Korean National Health and Nutrition Examination Survey. Face-to-face health interviews were conducted by trained surveyors who visited households during 2013. The contents of the interviews included data on demographic factors, physical condition, psychological condition, and HRQoL. [Results] Stress perceptions related to health condition differed significantly across the populations of cancer, stroke, and CVD patients. The HRQoL items of mobility, self-care, usual activities, and anxiety/depression also differed significantly across these populations. [Conclusion] Healthcare teams will now be in a position to plan programs for improvement in these areas according to the features of each disease. PMID- 26355818 TI - Improve Synergy Between Health Information Exchange and Electronic Health Records to Increase Rates of Continuously Insured Patients. AB - INTRODUCTION: The Affordable Care Act increases health insurance options, yet many Americans may struggle to consistently maintain coverage. While health care providers have traditionally not been involved in providing insurance enrollment support to their patients, the ability for them to do so now exists. We propose that providers could capitalize on the expansion of electronic health records (EHRs) and the advances in health information exchanges (HIEs) to improve their patients' insurance coverage rates and continuity. EVIDENCE FOR ARGUMENT: We describe a project in which we are building strategies for linking, and thus improving synergy between, payer and EHR data. Through this effort, care teams will have access to new automated tools and increased EHR functionality designed to help them assist their patients in obtaining and maintaining health insurance coverage. SUGGESTION FOR THE FUTURE: The convergence of increasing EHR adoption, improving HIE functionality, and expanding insurance coverage options, creates new opportunities for clinics to help their patients obtain public health insurance. Harnessing this nascent ability to exchange information between payers and providers may improve synergies between HIE and EHRs, and thus support clinic based efforts to keep patients continuously insured. PMID- 26355819 TI - Effect of hydrophilic additives on the dissolution and pharmacokinetic properties of itraconazole-enteric polymer hot-melt extruded amorphous solid dispersions. AB - Hot-melt extrusion technology has been widely reported for producing amorphous solid dispersions of poorly water-soluble compounds. A number of studies revealed that enteric polymers containing ionizable groups are able to improve the physical stability and maintain drug supersaturation, thereby enhancing oral bioavailability. However, our previous studies found that itraconazole (ITZ) enteric polymer amorphous solid dispersions are hydrophobic and poorly wettable. Moreover, drug release in an acidic environment (i.e. stomach) is very limited, indicating a narrow absorption window. In the present study, we investigated the effect of hydrophilic additives on the in vitro and in vivo performance of ITZ enteric polymer amorphous solid dispersions. Incorporating Vitamin E TPGS into ITZ-HPMCAS amorphous solid dispersions significantly improved drug release in the acidic media. Surprisingly, a low concentration of Vitamin E TPGS also enhanced the degree of drug supersaturation in neutral pH media, which is unique as compared with other tested hydrophilic additives. This effect is not due to the solubilization of the surfactant. We further formulated the amorphous solid dispersions into tablet dosage forms and evaluated their performance in a bio relevant dissolution media. Our optimized formulations exhibited drastically enhanced dissolution profiles as compared with the commercial ITZ product and ITZ amorphous solid dispersion without hydrophilic additive. In vivo study showed that Vitamin E TPGS induced rapid drug absorption after oral administration. Moreover, the elimination half-life of ITZ was prolonged due to the enzyme inhibition effect of Vitamin E TPGS. PMID- 26355817 TI - Acetaminophen-induced Liver Injury: from Animal Models to Humans. AB - Drug-induced liver injury is an important clinical problem and a challenge for drug development. Whereas progress in understanding rare and unpredictable (idiosyncratic) drug hepatotoxicity is severely hampered by the lack of relevant animal models, enormous insight has been gained in the area of predictable hepatotoxins, in particular acetaminophen-induced liver injury, from a broad range of experimental models. Importantly, mechanisms of toxicity obtained with certain experimental systems, such as in vivo mouse models, primary mouse hepatocytes, and metabolically competent cell lines, are being confirmed in translational studies in patients and in primary human hepatocytes. Despite this progress, suboptimal models are still being used and experimental data can be confusing, leading to controversial conclusions. Therefore, this review attempts to discuss mechanisms of drug hepatotoxicity using the most studied drug acetaminophen as an example. We compare the various experimental models that are used to investigate mechanisms of acetaminophen hepatotoxicity, discuss controversial topics in the mechanisms, and assess how these experimental findings can be translated to the clinic. The success with acetaminophen in demonstrating the clinical relevance of experimental findings could serve as an example for the study of other drug toxicities. PMID- 26355820 TI - Length control of supramolecular polymeric nanofibers based on stacked planar platinum(II) complexes by seeded-growth. AB - The formation of high aspect ratio supramolecular polymeric nanofibers from square-planar platinum(II) complexes through Pt...Pt and pi-pi stacking interactions has been achieved with a small width (<15 nm), tunable length, and relatively narrow length distributions up to ca. 400 nm under conditions of kinetic control using small seed fibers as initiators. PMID- 26355821 TI - CHORIORETINAL ATROPHY IN ALAGILLE SYNDROME. AB - PURPOSE: To describe multimodal imaging findings in a patient with Alagille syndrome and associated chorioretinopathy. METHODS: In this case report, clinical examination and multimodal imaging, including fundus photography, spectral domain optical coherence tomography, and fundus autofluorescence (AF) and wide-field AF, are presented. RESULTS: An 18-year-old Iranian-American girl with known history of Alagille syndrome reported diminished vision in both eyes. Color photographs depicted diffuse hypopigmentation of the fundus and atrophy of the macular retinal pigment epithelium with foveal sparing. Spectral domain optical coherence tomography revealed attenuation of the retinal pigment epithelium and overlying ellipsoid band. Fundus AF imaging of the macula revealed a geographic area of decreased AF that extended to the peripapillary region and inferotemporal arcade and contained discernable ovoid areas of deep AF loss in the nasal macula. Wide field AF revealed a continuous and circumferential area of well-delineated decreased AF in the retinal periphery of both eyes. CONCLUSION: This case represents a severe manifestation of posterior and peripheral chorioretinopathy in a patient with Alagille syndrome. This is the first documentation of significant peripheral chorioretinal atrophy as assessed by wide-field AF imaging in this condition. PMID- 26355822 TI - OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY SHOWS DEEP CAPILLARY PLEXUS HYPOPERFUSION IN INCOMPLETE CENTRAL RETINAL ARTERY OCCLUSION. AB - PURPOSE: To analyze optical coherence tomography angiography images of retinal capillary perfusion in incomplete central retinal artery occlusion. METHODS: Case report of a 63-year-old male white patient with transient vision loss in the left eye related to central retinal artery occlusion, secondary to left internal carotid thrombosis. Optical coherence tomography angiography images were captured with Angiovue (Optovue, Inc., Freemont, CA). Retinal capillary bed was segmented into the superficial and deep capillary plexus. Each blood flow angiography image was associated with an en face optical coherence tomography image and an optical coherence tomography B-scan showing the level of segmentation. RESULTS: In the left eye, visual acuity was 20/20 five days after transient vision loss. Optical coherence tomography angiography showed a normal superficial capillary plexus but the deep capillary plexus was not distinguishable compared with the right eye, although the posterior pole appeared well perfused on fluorescein angiography. Retrobulbar Doppler ultrasound confirmed a reduced blood flow velocity in the left central retinal artery. CONCLUSION: In this case of incomplete and transient central retinal artery occlusion, the deep capillary plexus was poorly visible on optical coherence tomography angiography, which could be due to its elective hypoperfusion and explain the ischemic whitening of the inner nuclear layer, previously described as paramacular acute middle maculopathy. However, the reason why the deep capillary plexus is more sensitive to reduced blood flow in the central retinal artery is not fully understood. In a case of partial central retinal artery occlusion, optical coherence tomography angiography allowed showing elective poor perfusion of the retinal deep capillary plexus. PMID- 26355823 TI - Is Transient Ischemic Attack a Medical Emergency? An Evidence-Based Analysis. AB - BACKGROUND: Transient ischemic attack (TIA) is a brief episode of dysfunction in a confined area of the brain. The risk of stroke following TIA is approximately 4% within the first 2 days and 9% within the first month. Therefore, early diagnosis and treatment is critical to reduce mortality and risk of stroke in patients who have experienced a TIA. OBJECTIVES: This systematic review aimed to investigate the impact of the urgent evaluation and initiation of treatment of patients with TIA on the risk of subsequent stroke and death. DATA SOURCES: A literature search was performed for studies published from January 1, 2007, until December 21, 2012. The search was updated monthly to April 1, 2013. RESULTS: All identified studies showed that urgent assessment and initiation of treatment of TIA is an effective strategy in reducing the incidence of stroke. Among these, a large observational study found a large effect in that the risk of stroke was reduced by 80%, and a Canadian study found that providing urgent care significantly reduced the rate of stroke in high-risk patients. Another Canadian study reported a significant reduction in the rate of death among patients referred to stroke prevention clinics, compared to patients not referred to such services. One study showed that patients discharged from an emergency department with standard care had significantly higher rates of stroke and subsequent TIA in the first month, compared to those who were hospitalized. However, another study showed that for patients at low to moderate risk, rate of stroke was similar between inpatients and those managed in a TIA clinic. LIMITATIONS: Our analysis was restricted to the effect of the combined interventions. The magnitude of benefit of each individual component of the intervention cannot be determined through this review. CONCLUSIONS: The results of this systematic review have important clinical and health system implications. Urgent management of TIA patients in specialized TIA clinics rather than regular practice results in a lower rate of stroke and disability. PMID- 26355825 TI - Classifying Patients with Chronic Pelvic Pain into Levels of Biopsychosocial Dysfunction Using Latent Class Modeling of Patient Reported Outcome Measures. AB - Chronic pelvic pain affects multiple aspects of a patient's physical, social, and emotional functioning. Latent class analysis (LCA) of Patient Reported Outcome Measures Information System (PROMIS) domains has the potential to improve clinical insight into these patients' pain. Based on the 11 PROMIS domains applied to n=613 patients referred for evaluation in a chronic pelvic pain specialty center, exploratory factor analysis (EFA) was used to identify unidimensional superdomains. Latent profile analysis (LPA) was performed to identify the number of homogeneous classes present and to further define the pain classification system. The EFA combined the 11 PROMIS domains into four unidimensional superdomains of biopsychosocial dysfunction: Pain, Negative Affect, Fatigue, and Social Function. Based on multiple fit criteria, a latent class model revealed four distinct classes of CPP: No dysfunction (3.2%); Low Dysfunction (17.8%); Moderate Dysfunction (53.2%); and High Dysfunction (25.8%). This study is the first description of a novel approach to the complex disease process such as chronic pelvic pain and was validated by demographic, medical, and psychosocial variables. In addition to an essentially normal class, three classes of increasing biopsychosocial dysfunction were identified. The LCA approach has the potential for application to other complex multifactorial disease processes. PMID- 26355826 TI - Change of School in Early Adolescence and Adverse Obesity-Related Dietary Behavior: A Longitudinal Cohort Study, Victoria, Australia, 2013-2014. AB - INTRODUCTION: Environments that facilitate energy-dense, nutrient-poor diets are associated with childhood obesity. We examined the effect of a change of school environment on the prevalence of obesity and related dietary behavior in early adolescence. METHODS: Fifteen schools in Victoria, Australia, were recruited at random from the bottom 2 strata of a 5-level socioeconomic scale. In 9 schools, students in grade 6 primary school transitioned to different schools for grade 7 secondary school, whereas in 6 schools, students remained in the same school from grade 6 to grade 7. Time 1 measures were collected from students (N = 245) in grade 6 (aged 11-13 y). Time 2 data were collected from 243 (99%) of the original cohort in grade 7. Data collected were dietary recall self-reported by students via questionnaire, measured height and weight of students, and aspects of the school food environment via school staff survey. Comparative and mixed model regression analyses were conducted. RESULTS: Of 243 students, 63% (n = 152) changed schools from time 1 to time 2, with no significant difference in weight status. Students who changed schools reported an increase in purchases of after school snack food, greater sweetened beverage intake, fewer fruit-and-vegetable classroom breaks, and less encouragement for healthy eating compared with students who remained in the same school. School staff surveys showed that more primary than secondary schools had written healthy canteen policies and fewer days of canteen or food services operation. CONCLUSION: A change of school environment has negative effects on children's obesity-related dietary behavior. Consistent policy is needed across school types to support healthy eating in school environments. PMID- 26355827 TI - Disparities in Age at Diabetes Diagnosis Among Asian Americans: Implications for Early Preventive Measures. AB - We evaluated the association between Asian American ethnicity and age at diagnosis for type 2 diabetes using data from the California Health Interview Survey. Survey-weighted unadjusted and adjusted linear regressions were used to obtain mean estimates of age at diagnosis. In the adjusted regression model, ages at diagnosis were 10.5, 8.7, 8.4, and 4.2 years earlier among South Asian, Vietnamese, Filipino, and Korean populations, respectively, as compared to non Hispanic whites; no significant difference in age at diagnosis was noted for Chinese and Japanese populations. Recommendations for diabetes screening and preventive measures specific to Asian American populations are warranted. PMID- 26355828 TI - Evaluating the Impact of the Healthy Beverage Executive Order for City Agencies in Boston, Massachusetts, 2011-2013. AB - INTRODUCTION: Intake of sugar-sweetened beverages (SSBs) is associated with negative health effects. Access to healthy beverages may be promoted by policies such as the Healthy Beverage Executive Order (HBEO) established by former Boston mayor Thomas M. Menino, which directed city departments to eliminate the sale of SSBs on city property. Implementation consisted of "traffic-light signage" and educational materials at point of purchase. This study evaluates the impact of the HBEO on changes in beverage availability. METHODS: Researchers collected data on price, brand, and size of beverages for sale in spring 2011 (899 beverage slots) and for sale in spring 2013, two years after HBEO implementation (836 beverage slots) at access points (n = 31) at city agency locations in Boston. Nutrient data, including calories and sugar content, from manufacturer websites were used to determine HBEO beverage traffic-light classification category. We used paired t tests to examine change in average calories and sugar content of beverages and the proportion of beverages by traffic-light classification at access points before and after HBEO implementation. RESULTS: Average beverage sugar grams and calories at access points decreased (sugar, -13.1 g; calories, 48.6 kcal; p<.001) following the implementation of the HBEO. The average proportion of high-sugar ("red") beverages available per access point declined ( 27.8%, p<.001). Beverage prices did not change over time. City agencies were significantly more likely to sell only low-sugar beverages after the HBEO was implemented (OR = 4.88; 95% CI, 1.49-16.0). DISCUSSION: Policies such as the HBEO can promote community-wide changes that make healthier beverage options more accessible on city-owned properties. PMID- 26355829 TI - Networking to Improve Nutrition Policy Research. AB - Effective nutrition and obesity policies that improve the food environments in which Americans live, work, and play can have positive effects on the quality of human diets. The Centers for Disease Control and Prevention's (CDC's) Nutrition and Obesity Policy Research and Evaluation Network (NOPREN) conducts transdisciplinary practice-based policy research and evaluation to foster understanding of the effectiveness of nutrition policies. The articles in this special collection bring to light a set of policies that are being used across the United States. They add to the larger picture of policies that can work together over time to improve diet and health. PMID- 26355830 TI - Proximal Cerebral Hemisphere: Should We Continue to Assume Symmetry or Is It Time to Look at It Routinely? PMID- 26355831 TI - Working memory contents revive the neglected, but suppress the inhibited. AB - It is well known that attention is biased toward a stimulus matching working memory contents. However, it remains unknown whether the maintenance of information in working memory by itself is sufficient to create memory-driven attentional capture. Notably, in many previous studies showing the memory-driven attentional capture, the task settings might have explicitly or implicitly incentivized participants to strategically attend to a memory-matching stimulus. By innovating an experimental paradigm, the present study overcame this challenge and directly tested whether working memory contents capture attention in the absence of task-level attentional bias toward a memory-matching stimulus. I found that a stimulus that is usually outside the focus of attention, powerfully captured attention when it matched working memory contents, whereas a match between working memory and an inhibited stimulus suppressed attentional allocation toward the memory-matching stimulus. These findings suggest that in the absence of any task-level attentional bias toward memory-matching stimuli, attention is biased toward a memory-matching stimulus, but this memory-driven attentional capture is diminished when top-down inhibition is imposed on the stimulus. PMID- 26355832 TI - Identification of phenotypes at risk of transition from diastolic hypertension to isolated systolic hypertension. AB - Little is known about the potential progression of hypertensive patients towards isolated systolic hypertension (ISH) and about the phenotypes associated with the development of this condition. Aim of this study was to detect predictors of evolution towards ISH in patients with initial systolic-diastolic hypertension. We selected 7801 hypertensive patients free of prevalent cardiovascular (CV) diseases or severe chronic kidney disease and with at least 6-month follow-up from the Campania Salute Network. During 55+/-44 months of follow-up, incidence of ISH was 21%. Patients with ISH at the follow-up were significantly older (P<0.0001), had longer duration of hypertension, higher prevalence of diabetes and were more likely to be women (all P<0.0001). They exhibited higher baseline left ventricular mass index (LVMi), arterial stiffness (pulse pressure/stroke index), relative wall thickness (RWT) and carotid intima-media thickness (IMT; all P<0.001). Independent predictors of incident ISH were older age (odds ratio (OR)=1.14/5 years), female gender (OR=1.30), higher baseline systolic blood pressure (OR=1.03/5 mm Hg), lower diastolic blood pressure (OR=0.89/5 mm Hg), longer duration of hypertension (OR=1.08/5 months), higher LVMi (OR=1.02/5 g m( 2.7)), arterial stiffness (OR=2.01), RWT (OR=1.02), IMT (OR=1.19 mm(-1); all P<0.0001), independently of antihypertensive treatment, obesity, diabetes and fasting glucose (P>0.05). Our findings suggest that ISH is a sign of aggravation of the atherosclerotic disease already evident by the target organ damage. Great efforts should be paid to prevent this evolution and prompt aggressive therapy for arterial hypertension should be issued before the onset of target organ damage, to reduce global CV risk. PMID- 26355833 TI - The Frequency of Autoimmune Thyroid Disease in Alopecia Areata and Vitiligo Patients. AB - AIM: Many studies demonstrated that alopecia areata (AA) and vitiligo are commonly associated with autoimmune thyroid diseases. We aimed to investigate the frequency of thyroid dysfunctions and autoimmunity related with vitiligo and AA. MATERIAL AND METHODS: 200 patients, 92 AA and 108 vitiligo diagnosed, were surveyed retrospectively. The control population was in reference range and from Konya, central Anatolian region of Turkey. Thyroid function tests (free T3, free T4, and TSH) and serum thyroid autoantibody (anti-TG, anti-TPO) levels were evaluated in all patients. RESULTS: In vitiligo patients, 9 (8.3%) had elevated anti-TG levels and 16 (14.8%) had elevated anti-TPO, and in 17 patients (15.7%) TSH levels were elevated and 3 (2.8%) patients had elevated fT4 levels and 5 (4.6%) had elevated fT3 levels. Within AA patients, 2 (2.2%) had anti-TG elevation and 13 (14.1%) had anti-TPO elevation, in 7 patients (7.6%) TSH were elevated, and in 1 patient (1.1%) fT4 were elevated and 5 (5.4%) patients had elevated fT3 levels. CONCLUSION: In our study, impaired thyroid functions and thyroid autoantibodies in vitiligo and AA patients were identified at lower rates than the previous studies. According to results of this study there is no need for detailed examination in alopecia areata and vitiligo patients without clinical history. PMID- 26355834 TI - Padina arborescens Ameliorates Hyperglycemia and Dyslipidemia in C57BL/KsJ-db/db Mice, a Model of Type 2 Diabetes Mellitus. AB - Recently, there has been a growing interest in alternative therapies and in the therapeutic use of natural products for the treatment of diabetes. Therefore, in this study, we investigated the hypoglycemic and hypolipidemic effects of brown algae, Padina arborescens, in an animal model of type 2 diabetes. For 6 weeks, male C57BL/KsJ-db/db mice were administrated either control diet with no treatment or were treated with rosiglitazone (RG; 0.005%, w/w) or P. arborescens extract (PAE; 0.5%, w/w). At the end of the experimental period, the blood glucose levels, glycosylated hemoglobin levels, and plasma insulin levels were significantly lower in the RG and PAE groups compared with the control group. In addition, glucose tolerance was significantly improved in the RG and PAE groups. The homeostatic index of insulin resistance was lower in the RG and PAE groups than the diabetic control group. Also, the total cholesterol, LDL-cholesterol, triglyceride, and free fatty acid levels were lower in the PAE group than in the control group, whereas the HDL-C level was higher in the PAE group. Supplementation with PAE significantly lowered hepatic glucose-6-phosphatase and phosphoenolpyruvate carboxykinase activities, and increased glucokinase activity in the liver. Consequently, these results suggest that PAE may be beneficial in improving insulin resistance, hyperglycemia, and dyslipidemia in type 2 diabetics. PMID- 26355835 TI - The complete mitochondrial genome of Bufo raddei. AB - The complete mitochondrial genome of Bufo raddei is carried out in the present research using Illumina Hiseq 2500. The mitogenome is 17 602 bp in length and contains 13 protein-coding genes, 22 transfer RNA genes, two ribosomal RNA genes, and a D-loop region. The overall base composition of the H-strand is 29.15% for A, 26.09% for C, 15.16% for G, and 29.60% for T. The G + C content is 41.25%. Phylogenetic analyses of B. raddei and other 12 amphibian were carried out using Bayesian phylogenetic methods. The sequences of B. raddei were clustered in genus Bufo. PMID- 26355836 TI - Correction: The Role of Aerobic Fitness in Cortical Thickness and Mathematics Achievement in Preadolescent Children. AB - [This corrects the article DOI: 10.1371/journal.pone.0134115.]. PMID- 26355837 TI - Accuracy of Patient Self-Report of Stroke: A Systematic Review from the UK Biobank Stroke Outcomes Group. AB - OBJECTIVE: We performed a systematic review of the accuracy of patient self report of stroke to inform approaches to ascertaining and confirming stroke cases in large prospective studies. METHODS: We sought studies comparing patient self report against a reference standard for stroke. We extracted data on survey method(s), response rates, participant characteristics, the reference standard used, and the positive predictive value (PPV) of self-report. Where possible we also calculated sensitivity, specificity, negative predictive value (NPV), and stroke prevalence. Study-level risk of bias was assessed using the Quality Assessment of Diagnostic Studies tool (QUADAS-2). RESULTS: From >1500 identified articles, we included 17 studies. Most asked patients to report a lifetime history of stroke but a few limited recall time to <=5 years. Some included questions for transient ischaemic attack (TIA) or stroke synonyms. No study was free of risk of bias in the QUADAS-2 assessment, the most frequent causes of bias being incomplete reference standard data, absence of blinding of adjudicators to self-report status, and participant response rates (<80%). PPV of self-report ranged from 22-87% (17 studies), sensitivity from 36-98% (10 studies), specificity from 96-99.6% (10 studies), and NPV from 88.2-99.9% (10 studies). PPV increased with stroke prevalence as expected. Among six studies with available relevant data, if confirmed TIAs were considered to be true rather than false positive strokes, PPV of self-report was >75% in all but one study. It was not possible to assess the influence of recall time or of the question(s) asked on PPV or sensitivity. CONCLUSIONS: Characteristics of the study population strongly influence self-report accuracy. In population-based studies with low stroke prevalence, a large proportion of self-reported strokes may be false positives. Self-report is therefore unlikely to be helpful for identifying cases without subsequent confirmation, but may be useful for case ascertainment in combination with other data sources. PMID- 26355838 TI - Clinical Epidemiology of Buruli Ulcer from Benin (2005-2013): Effect of Time Delay to Diagnosis on Clinical Forms and Severe Phenotypes. AB - Buruli Ulcer (BU) is a neglected infectious disease caused by Mycobacterium ulcerans that is responsible for severe necrotizing cutaneous lesions that may be associated with bone involvement. Clinical presentations of BU lesions are classically classified as papules, nodules, plaques and edematous infiltration, ulcer or osteomyelitis. Within these different clinical forms, lesions can be further classified as severe forms based on focality (multiple lesions), lesions' size (>15 cm diameter) or WHO Category (WHO Category 3 lesions). There are studies reporting an association between delay in seeking medical care and the development of ulcerative forms of BU or osteomyelitis, but the effect of time delay on the emergence of lesions classified as severe has not been addressed. To address both issues, and in a cohort of laboratory-confirmed BU cases, 476 patients from a medical center in Allada, Benin, were studied. In this laboratory confirmed cohort, we validated previous observations, demonstrating that time delay is statistically related to the clinical form of BU. Indeed, for non ulcerated forms (nodule, edema, and plaque) the median time-delay was 32.5 days (IQR 30.0-67.5), while for ulcerated forms it was 60 days (IQR 20.0-120.0) (p = 0.009), and for bone lesions, 365 days (IQR 228.0-548.0). On the other hand, we show here that time-delay is not associated with the more severe phenotypes of BU, such as multi-focal lesions (median 90 days; IQR 56-217.5; p = 0.09), larger lesions (diameter >15 cm) (median 60 days; IQR 30-120; p = 0.92) or category 3 WHO classification (median 60 days; IQR 30-150; p = 0.20), when compared with unifocal (median 60 days; IQR 30-90), small lesions (diameter <=15 cm) (median 60 days; IQR 30-90), or WHO category 1+2 lesions (median 60 days; IQR 30-90), respectively. Our results demonstrate that after an initial period of progression towards ulceration or bone involvement, BU lesions become stable regarding size and focal/multi-focal progression. Therefore, in future studies on BU epidemiology, severe clinical forms should be systematically considered as distinct phenotypes of the same disease and thus subjected to specific risk factor investigation. PMID- 26355840 TI - Iridium(III) Bis-Pyridine-2-Sulfonamide Complexes as Efficient and Durable Catalysts for Homogeneous Water Oxidation. AB - A family of tetradentate bis(pyridine-2-sulfonamide) (bpsa) compounds was synthesized as a ligand platform for designing resilient and electronically tunable catalysts capable of performing water oxidation catalysis and other processes in highly oxidizing environments. These wrap-around ligands were coordinated to Ir(III) octahedrally, forming an anionic complex with chloride ions bound to the two remaining coordination sites. NMR spectroscopy documented that the more rigid ligand frameworks-[Ir(bpsa-Cy)Cl2](-) and [Ir(bpsa-Ph)Cl2](-) produced C1-symmetric complexes, while the complex with the more flexible ethylene linker in [Ir(bpsa-en)Cl2](-) displays C2 symmetry. Their electronic structure was explored with DFT calculations and cyclic voltammetry in nonaqueous environments, which unveiled highly reversible Ir(III)/Ir(IV) redox processes and more complex, irreversible reduction chemistry. Addition of water to the electrolyte revealed the ability of these complexes to catalyze the water oxidation reaction efficiently. Electrochemical quartz crystal microbalance studies confirmed that a molecular species is responsible for the observed electrocatalytic behavior and ruled out the formation of active IrOx. The electrochemical studies were complemented by work on chemically driven water oxidation, where the catalytic activity of the iridium complexes was studied upon exposure to ceric ammonium nitrate, a strong, one-electron oxidant. Variation of the catalyst concentrations helped to illuminate the kinetics of these water oxidation processes and highlighted the robustness of these systems. Stable performance for over 10 days with thousands of catalyst turnovers was observed with the C1-symmetric catalysts. Dynamic light scattering experiments ascertained that a molecular species is responsible for the catalytic activity and excluded the formation of IrOx particles. PMID- 26355839 TI - Helicobacter pylori Infection in Thailand: A Nationwide Study of the CagA Phenotype. AB - BACKGROUND: The risk to develop gastric cancer in Thailand is relatively low among Asian countries. In addition, the age-standardized incidence rate (ASR) of gastric cancer in Thailand varies with geographical distribution; the ASR in the North region is 3.5 times higher than that in the South region. We hypothesized that the prevalence of H. pylori infection and diversity of CagA phenotype contributes to the variety of gastric cancer risk in various regions of Thailand. METHODS: We conducted a nationwide survey within Thailand. We determined H. pylori infection prevalence by detecting H. pylori, using histochemical and immunohistochemical methods. The anti-CagA antibody and anti-East-Asian type CagA antibody (alpha-EAS Ab), which showed high accuracy in several East Asian countries, were used to determine CagA phenotype. RESULTS: Among 1,546 patients from four regions, including 17 provinces, the overall prevalence of H. pylori infection was 45.9% (710/1,546). Mirroring the prevalence of H. pylori infection, histological scores were the lowest in the South region. Of the 710 H. pylori positive patients, 93.2% (662) were immunoreactive with the anti-CagA antibody. CagA-negative strain prevalence in the South region was significantly higher than that in other regions (17.9%; 5/28; p < 0.05). Overall, only 77 patients (11.6%) were immunoreactive with the alpha-EAS Ab. There were no differences in the alpha EAS Ab immunoreactive rate across geographical regions. CONCLUSIONS: This is the first study using immunohistochemistry to confirm H. pylori infections across different regions in Thailand. The prevalence of East-Asian type CagA H. pylori in Thailand was low. The low incidence of gastric cancer in Thailand may be attributed to the low prevalence of precancerous lesions. The low incidence of gastric cancer in the South region might be associated with the lower prevalence of H. pylori infection, precancerous lesions, and CagA-positive H. pylori strains, compared with that in the other regions. PMID- 26355841 TI - Parallel molecular routes to cold adaptation in eight genera of New Zealand stick insects. AB - The acquisition of physiological strategies to tolerate novel thermal conditions allows organisms to exploit new environments. As a result, thermal tolerance is a key determinant of the global distribution of biodiversity, yet the constraints on its evolution are not well understood. Here we investigate parallel evolution of cold tolerance in New Zealand stick insects, an endemic radiation containing three montane-occurring species. Using a phylogeny constructed from 274 orthologous genes, we show that stick insects have independently colonized montane environments at least twice. We compare supercooling point and survival of internal ice formation among ten species from eight genera, and identify both freeze tolerance and freeze avoidance in separate montane lineages. Freeze tolerance is also verified in both lowland and montane populations of a single, geographically widespread, species. Transcriptome sequencing following cold shock identifies a set of structural cuticular genes that are both differentially regulated and under positive sequence selection in each species. However, while cuticular proteins in general are associated with cold shock across the phylogeny, the specific genes at play differ among species. Thus, while processes related to cuticular structure are consistently associated with adaptation for cold, this may not be the consequence of shared ancestral genetic constraints. PMID- 26355842 TI - Impact of Subunit Composition on the Uptake of alpha-Crystallin by Lens and Retina. AB - Misfolded protein aggregation, including cataract, cause a significant amount of blindness worldwide. alpha-Crystallin is reported to bind misfolded proteins and prevent their aggregation. We hypothesize that supplementing retina and lens with alpha-crystallin may help to delay disease onset. The purpose of this study was to determine if alphaB-crystallin subunits containing a cell penetration peptide (gC-tagged alphaB-crystallin) facilitate the uptake of wild type alphaA crystallin (WT-alphaA) in lens and retina. Recombinant human alphaB-crystallin was modified by the addition of a novel cell penetration peptide derived from the gC gene product of herpes simplex virus (gC-alphaB). Recombinant gC-alphaB and wild-type alphaA-crystallin (WT-alphaA) were purified from E. coli over expression cultures. After Alexa-labeling of WT-alphaA, these proteins were mixed at ratios of 1:2, 1:5 and 1:10, respectively, and incubated at 37 degrees C for 4 hours to allow for subunit exchange. Mixed oligomers were subsequently incubated with tissue culture cells or mouse organ cultures. Similarly, crystallin mixtures were injected into the vitreous of rat eyes. At various times after exposure, tissues were harvested and analyzed for protein uptake by confocal microscopy or flow cytometry. Chaperone-like activity assays were performed on alpha crystallins ratios showing optimal uptake using chemically-induced or heat induced substrate aggregation assays. As determined by flow cytometry, a ratio of 1:5 for gC-alphaB to WT-alphaA was found to be optimal for uptake into retinal pigmented epithelial cells (ARPE-19). Chaperone-like activity assays demonstrated that hetero-oligomeric complex of gC-alphaB to WT-alphaA (in 1:5 ratio) retained protein aggregation protection. We observed a significant increase in protein uptake when optimized (gC-alphaB to WT-alphaA (1:5 ratio)) hetero-oligomers were used in mouse lens and retinal organ cultures. Increased levels of alpha crystallin were found in lens and retina following intravitreal injection of homo and hetero-oligomers in rats. PMID- 26355843 TI - Tumor pH(e)-triggered charge-reversal and redox-responsive nanoparticles for docetaxel delivery in hepatocellular carcinoma treatment. AB - The insufficient cellular uptake of nanocarriers and their slow drug release have become major obstacles for achieving satisfactory anticancer outcomes in nano medicine therapy. Because of the slightly acidic extracellular environment (pHe~ 6.5) and a higher glutathione (GSH) concentration (approximately 10 mM) in tumor tissue/cells, we firstly designed a novel d-alpha-tocopheryl polyethylene glycol 1000-poly(beta-amino ester) block copolymer containing disulfide linkages (TPSS). TPSS nanoparticles (NPs) with pH- and redox-sensitive behaviors were developed for on-demand delivery of docetaxel (DTX) in hepatocellular carcinoma. DTX/TPSS NPs exhibited sensitive surface charge reversal from -47.6 +/- 2.5 mV to +22.5 +/ 3.2 mV when the pH decreased from 7.4 to 6.5, to simulate the pHe. Meanwhile, anabatic drug release of DTX/TPSS NPs was observed in PBS buffer (pH 6.5, 10 mM GSH). Due to the synergism between the pHe-triggered charge reversal and the redox-triggered drug release, enhanced drug uptake and anticancer efficacy were observed in HepG2 and SMMC 7721 cells treated with DTX/TPSS NPs. The positively charged NPs exhibited a stronger inhibitory effect on cell proliferation, promoted cell cycle arrest in the G2/M phase, and increased the rate of apoptosis. More importantly, based on the higher tumor accumulation of TPSS vehicles in vivo, a significant suppression of tumor growth, but without side effects, was observed when DTX/TPSS NPs were injected intravenously into HepG2 xenograft tumor-bearing mice. Collectively, these results demonstrate that the newly developed dual-functional TPSS copolymer may be utilized as a drug delivery system for anticancer therapy. PMID- 26355844 TI - Unveiling Cancer. AB - This article narrates a multifaceted educational journey undertaken by a medical student through a weekly SCRAPS (surgery, clinical disciplines, radiology, anatomy, psychiatry and laboratory sciences) clinico-pathological meeting held in the College of Medicine & Health Sciences at Sultan Qaboos University in Muscat, Oman. Through a presentation titled 'Unveiling Cancer', the multidisciplinary and interprofessional audience witnessed a simulated interaction between a medical student, a technologist peer and tutors in medicine, pathology and radiology. The presentation was based on the complexities of presentation, diagnosis and management of a patient with anaplastic large cell lymphoma, a rare type of non Hodgkin lymphoma, in the aftermath of a bone marrow transplantation. After describing the case, the student shared with the audience a spectrum of learning objectives, which included integration in the complex world of contemporary medicine, insight into the triumphs and travails of technology (immunohistochemistry) and peer collaboration, communication and mentorship. PMID- 26355845 TI - miR-1244/Myocyte Enhancer Factor 2D Regulatory Loop Contributes to the Growth of Lung Carcinoma. AB - Lung carcinoma greatly threatens human health, due to its increasing incidence in recent years and poor prognosis. However, this malignancy displays resistance against current therapeutic strategies. One of major causes leading to bad outcomes for lung cancer therapy is the lack of understanding on its tumorigenesis and progression. To explore the molecular mechanism by which lung cancer progresses, we employed multidisciplinary approaches and used lung cancer cell lines as research models. miR-1244 was underexpressed in lung carcinoma by 40.6-73.8%, which is highly associated with patients' survival. miR-1244 restoration was shown to affect the proliferation, survival, and invasion of lung cancer cells. miR-1244 suppression rendered normal lung fibroblasts with malignant phenotypes. miR-1244 overexpression can reduce the growth of lung cancer xenografts. miR-1244 was then verified to negatively regulate the expression of myocyte enhancer factor 2D (MEF2D) in lung cancer cells. MEF2D can also affect the expression of miR-1244 by directly binding to its promoter. Further study showed that MEF2D is required for the effect of miR-1244 on lung cancer and normal cells. These results suggested that there is an autoregulatory circuit consisting of miR-1244 and MEF2D, which contributes to the progression of lung cancer. Targeting this molecular loop may be a promising strategy for lung carcinoma treatment. PMID- 26355847 TI - Conversion of a Benzofuran Ester to an Amide through an Enamine Lactone Pathway: Synthesis of HCV Polymerase Inhibitor GSK852A. AB - HCV NS5B polymerase inhibitor GSK852A (1) was synthesized in only five steps from ethyl 4-fluorobenzoylacetate (3) in 46% overall yield. Key to the efficient route was the synthesis of the highly functionalized benzofuran core 15 from the beta keto ester in one pot and the efficient conversion of ester 6 to amide 19 via enamine lactone 22. Serendipitous events led to identification of the isolable enamine lactone intermediate 22. Single crystal X-ray diffraction and NMR studies supported the intramolecular hydrogen bond shown in enamine lactone 22. The hydrogen bond was considered an enabler in the proposed pathway from ester 6 to enamine lactone 22 and its rearrangement to amide 19. GSK852A (1) was obtained after reductive amination and mesylation with conditions amenable to the presence of the boronic acid moiety which was considered important for the desirable pharmacokinetics of 1. The overall yield of 46% in five steps was a significant improvement to the previous synthesis from the same beta-keto ester in 5% yield over 13 steps. PMID- 26355846 TI - Clustering of Expression Data in Chronic Lymphocytic Leukemia Reveals New Molecular Subdivisions. AB - Although the identification of inherent structure in chronic lymphocytic leukemia (CLL) gene expression data using class discovery approaches has not been extensively explored, the natural clustering of patient samples can reveal molecular subdivisions that have biological and clinical implications. To explore this, we preprocessed raw gene expression data from two published studies, combined the data to increase the statistical power, and performed unsupervised clustering analysis. The clustering analysis was replicated in 4 independent cohorts. To assess the biological significance of the resultant clusters, we evaluated their prognostic value and identified cluster-specific markers. The clustering analysis revealed two robust and stable subgroups of CLL patients in the pooled dataset. The subgroups were confirmed by different methodological approaches (non-negative matrix factorization NMF clustering and hierarchical clustering) and validated in different cohorts. The subdivisions were related with differential clinical outcomes and markers associated with the microenvironment and the MAPK and BCR signaling pathways. It was also found that the cluster markers were independent of the immunoglobulin heavy chain variable (IGVH) genes mutational status. These findings suggest that the microenvironment can influence the clinical behavior of CLL, contributing to prognostic differences. The workflow followed here provides a new perspective on differences in prognosis and highlights new markers that should be explored in this context. PMID- 26355848 TI - The Use of Kernel Density Estimation to Examine Associations between Neighborhood Destination Intensity and Walking and Physical Activity. AB - BACKGROUND: Local destinations have previously been shown to be associated with higher levels of both physical activity and walking, but little is known about how the distribution of destinations is related to activity. Kernel density estimation is a spatial analysis technique that accounts for the location of features relative to each other. Using kernel density estimation, this study sought to investigate whether individuals who live near destinations (shops and service facilities) that are more intensely distributed rather than dispersed: 1) have higher odds of being sufficiently active; 2) engage in more frequent walking for transport and recreation. METHODS: The sample consisted of 2349 residents of 50 urban areas in metropolitan Melbourne, Australia. Destinations within these areas were geocoded and kernel density estimates of destination intensity were created using kernels of 400m (meters), 800m and 1200m. Using multilevel logistic regression, the association between destination intensity (classified in quintiles Q1(least)-Q5(most)) and likelihood of: 1) being sufficiently active (compared to insufficiently active); 2) walking>=4/week (at least 4 times per week, compared to walking less), was estimated in models that were adjusted for potential confounders. RESULTS: For all kernel distances, there was a significantly greater likelihood of walking>=4/week, among respondents living in areas of greatest destinations intensity compared to areas with least destination intensity: 400m (Q4 OR 1.41 95%CI 1.02-1.96; Q5 OR 1.49 95%CI 1.06-2.09), 800m (Q4 OR 1.55, 95%CI 1.09-2.21; Q5, OR 1.71, 95%CI 1.18-2.48) and 1200m (Q4, OR 1.7, 95%CI 1.18-2.45; Q5, OR 1.86 95%CI 1.28-2.71). There was also evidence of associations between destination intensity and sufficient physical activity, however these associations were markedly attenuated when walking was included in the models. CONCLUSIONS: This study, conducted within urban Melbourne, found that those who lived in areas of greater destination intensity walked more frequently, and showed higher odds of being sufficiently physically active-an effect that was largely explained by levels of walking. The results suggest that increasing the intensity of destinations in areas where they are more dispersed; and or planning neighborhoods with greater destination intensity, may increase residents' likelihood of being sufficiently active for health. PMID- 26355849 TI - Linking Annual Prescription Volume of Antidepressants to Corresponding Web Search Query Data: A Possible Proxy for Medical Prescription Behavior? AB - Persons using the Internet to retrieve medical information generate large amounts of health-related data, which are increasingly used in modern health sciences. We analyzed the relation between annual prescription volumes (APVs) of several antidepressants with marketing approval in Germany and corresponding web search query data generated in Google to test whether web search query volume may be a proxy for medical prescription practice. We obtained APVs of several antidepressants related to corresponding prescriptions at the expense of the statutory health insurance in Germany from 2004 to 2013. Web search query data generated in Germany and related to defined search terms (active substance or brand name) were obtained with Google Trends. We calculated correlations (Person's r) between the APVs of each substance and the respective annual "search share" values; coefficients of determination (R) were computed to determine the amount of variability shared by the 2 variables. Significant and strong correlations between substance-specific APVs and corresponding annual query volumes were found for each substance during the observational interval: agomelatine (r = 0.968, R = 0.932, P = 0.01), bupropion (r = 0.962, R = 0.925, P = 0.01), citalopram (r = 0.970, R = 0.941, P = 0.01), escitalopram (r = 0.824, R = 0.682, P = 0.01), fluoxetine (r = 0.885, R = 0.783, P = 0.01), paroxetine (r = 0.801, R = 0.641, P = 0.01), and sertraline (r = 0.880, R = 0.689, P = 0.01). Although the used data did not allow to perform an analysis with a higher temporal resolution (quarters, months), our results suggest that web search query volume may be a proxy for corresponding prescription behavior. However, further studies analyzing other pharmacologic agents and prescription data that facilitate an increased temporal resolution are needed to confirm this hypothesis. PMID- 26355850 TI - Effects of Mirtazapine on Patients Undergoing Naturalistic Diabetes Treatment: A Follow-Up Study Extended From 6 to 12 Months. PMID- 26355851 TI - Determining Live Birth: An Unusual Case. AB - Twins of unknown gestational age were delivered prematurely at home, placed in a bin bag, and hidden in a drawer. They were discovered several hours later after the mother presented to a hospital with postpartum hemorrhage. Autopsy took place after postmortem computed tomographic scans and full skeletal surveys were performed. One infant was macerated, and autopsy reflected a death in utero. The other was not macerated, and internal examination showed evidence of air entry into the lungs. Histology and postmortem computed tomographic scan also suggested that there had been air entry into the lungs. PMID- 26355852 TI - Poor Man's Methadone: A Case Report of Loperamide Toxicity. AB - Loperamide, a common over-the-counter antidiarrheal drug and opioid derivative, is formulated to act upon intestinal opioid receptors. However, at high doses, loperamide crosses the blood-brain barrier and reaches central opioid receptors in the brain, leading to central opiate effects including euphoria and respiratory depression. We report the case of a young man found dead in his residence with a known history of drug abuse. At autopsy, the only significant findings were a distended bladder and bloody oral purge. Drug screening found nontoxic levels of alprazolam, fluoxetine, and marijuana metabolites. Liquid chromatography time-of-flight mass spectrometry found an unusual set of split isotope peaks consistent with chlorine. On the basis of autopsy and toxicological findings, loperamide toxicity was suspected because of its opioid properties and molecular formula containing chlorine. A sample of loperamide was analyzed by liquid chromatography time-of-flight mass spectrometry, resulting in a matching mass and retention time to the decedent's sample. Subsequently, quantitative testing detected 63 ng/mL of loperamide or more than 6 times of therapeutic peak concentration. Cause of death was determined as "toxic effects of loperamide with fluoxetine and alprazolam." Because of its opioid effects and easy accessibility, loperamide is known as "poor man's methadone" and may go undetected at medical and forensic drug screening. PMID- 26355854 TI - Effect of Blend Composition and Additives on the Morphology of PCPDTBT:PC71BM Thin Films for Organic Photovoltaics. AB - The use of solvent additives in the fabrication of bulk heterojunction polymer:fullerene solar cells allows to boost efficiencies in several low bandgap polymeric systems. It is known that solvent additives tune the nanometer scale morphology of the bulk heterojunction. The full mechanism of efficiency improvement is, however, not completely understood. In this work, we investigate the influences of blend composition and the addition of 3 vol % 1,8-octanedithiol (ODT) as solvent additive on polymer crystallization and both, vertical and lateral morphologies of poly[2,6-(4,4-bis(2-ethylhexyl)-4H-cyclopenta [2,1-b;3,4 b']dithiophene)-alt-4,7(2,1,3-benzothiadiazole)] and [6,6]-phenyl C71-butyric acid methyl ester (PCPDTBT:PC71BM) blend thin films processed from chlorobenzene based solutions. The nanoscale morphology is probed with grazing incidence small- and wide-angle X-ray scattering as well as X-ray reflectivity and complemented with UV/vis spectroscopy. In PCPDTBT:PC71BM films the use of ODT is found to lower the solubility of fullerene in the polymer matrix and to promote polymer crystallization, both vertical and lateral microphase separation with morphological coarsening, and formation of a fullerene-rich topping layer. The enhanced photovoltaic performance is explained by these findings. PMID- 26355853 TI - Hydatid Disease Involved in the Heart, Liver, and Kidney That Caused Sudden Death: Case Report. AB - Hydatid disease is a parasitic infestation caused by ingestion of eggs of echinococcal species. For Echinococcus granulosus, the definitive host is the dog, and sheeps are the usual intermediate hosts. Humans are accidental intermediate hosts, infected by ingestion of food contaminated with eggs shed by dogs or foxes. The most common organs that hydatid disease encountered are the liver and lungs. Involvement of the kidney is rare and usually accompanies the other organ involvements. Cardiac involvement of echinococcosis is also very rare. We report the case of a 31-year-old woman with a 6-year history of asthma who collapsed after strenuous activity and died despite the interventions carried out. At autopsy, cystic masses were detected in the apex of the heart, in the right kidney, and in the liver. There were no macroscopic pathologic findings in the other organs. Microscopic examination revealed the diagnosis of hydatid cyst in the heart, right kidney, and liver besides medial hypertrophy of the lung vessels. Cause of death was attributed to hydatid cyst and its complications. Patients who have symptoms akin to asthma at clinical presentation have to be further investigated for organic cardiac and pulmonary diseases such as hydatid cyst, especially in endemic countries. PMID- 26355855 TI - Enantioselective syn and anti Homocrotylation of Aldehydes: Application to the Formal Synthesis of Spongidepsin. AB - Whereas crotylboration has been a useful method for synthesis of stereochemically complex products, we have shown that homocrotylboration can be achieved with cyclopropanated crotylation reagents, and that the stereoselectivity of the reaction can be predicted by analogous models. This paper presents a full account of this work, including the first examples of asymmetric anti homocrotylation. The scope of this reaction is demonstrated with highly enantioselective homocrotylation of both aliphatic and aromatic aldehydes, as well as double diastereoselection studies. An application of the synthesis of the marine natural product spongidepsin is presented, as well as streamlined syntheses of homocrotylation reagents. PMID- 26355856 TI - Thriving Among Giants: Self-Publishing in the Digital Age. PMID- 26355859 TI - Erratum. PMID- 26355862 TI - Presymptomatic Identification of Cancers in Pregnant Women During Noninvasive Prenatal Testing. AB - IMPORTANCE: Noninvasive prenatal testing (NIPT) for fetal aneuploidy by scanning cell-free fetal DNA in maternal plasma is rapidly becoming a major prenatal genetic test. Similar to placental DNA, tumor DNA can be detected in the plasma, and analysis of cell-free tumor DNA can be used to characterize and monitor cancers. We show that plasma DNA profiling allows for presymptomatic detection of tumors in pregnant women undergoing routine NIPT. OBSERVATIONS: During NIPT in over 4000 prospective pregnancies by parallel sequencing of maternal plasma cell free DNA, 3 aberrant genome representation (GR) profiles were observed that could not be attributed to the maternal or fetal genomic constitution. A maternal cancer was suspected, and those 3 patients were referred for whole-body diffusion weighted magnetic resonance imaging, which uncovered an ovarian carcinoma, a follicular lymphoma, and a Hodgkin lymphoma, each confirmed by subsequent pathologic and genetic investigations. The copy number variations in the subsequent tumor biopsies were concordant with the NIPT plasma GR profiles. CONCLUSIONS AND RELEVANCE: We show that maternal plasma cell-free DNA sequencing for noninvasive prenatal testing also may enable accurate presymptomatic detection of maternal tumors and treatment during pregnancy. PMID- 26355863 TI - Let Them Eat Fish. PMID- 26355864 TI - Let Them Eat Fish. PMID- 26355865 TI - Pricing and Value of Cancer Drugs. PMID- 26355866 TI - Let Them Eat Fish--Reply. PMID- 26355867 TI - Pricing and Value of Cancer Drugs--Reply. PMID- 26355868 TI - Arcella peruviana sp. nov. (Amoebozoa: Arcellinida, Arcellidae), a new species from a tropical peatland in Amazonia. AB - There has only been one study on the ecology of testate amoebae from Amazonian peatlands, despite Amazonia being a biodiversity hotspot of global importance. During analysis of litter samples from Aucayacu peatland, western (Peruvian) Amazonia, we discovered a testate amoeba with a distinct morphology unlike any other species reported previously. We describe a new species, Arcella peruviana, based on its distinct morphology, compare it to morphologically similar species and provide information about its ecology. This new species is characterised by a distinct cruciform aperture (diameter ranges between 12 and 17MUm) which is slightly invaginated. The test is small (height 43-57MUm) and polygonal in cross section. Our discovery suggests the existence of an unknown diversity of testate amoebae in Amazonia. The absence of the new Arcella species in more intensively sampled regions supports the view that protists have restricted distributions. PMID- 26355869 TI - Diversity and community ecology of forest epiphyte testate amoebae from European Russia. AB - Testate amoebae are an abundant group of microorganisms which make a significant contribution to the diversity of protist life. Most of the world's potential habitats for testate amoebae have been barely studied and when such places are investigated they frequently reveal novel communities and species. Here we consider the testate amoeba communities associated with boreal forest epiphytes (mosses and lichens); an environment which we argue has been under-researched. We present a dataset of 165 samples from four regions of western Russia and analyse these data in relation to micro-habitat position and selected environmental data. The testate amoebae of epiphytes are abundant but dominated by ubiquitous species. We show that there are trends toward a lower species richness and test concentration with greater elevation on the trunk and in lichens compared to mosses. There are considerable differences in community composition between sampling regions. Of all measured environmental variables only moisture content showed a significant relationship with testate amoeba community structure. Our data highlight how little is known about testate amoeba communities of this habitat and call for greater research efforts, particularly in less-studied regions and biomes. PMID- 26355870 TI - Mitigation of impedance changes due to electroporation therapy using bursts of high-frequency bipolar pulses. AB - BACKGROUND: For electroporation-based therapies, accurate modeling of the electric field distribution within the target tissue is important for predicting the treatment volume. In response to conventional, unipolar pulses, the electrical impedance of a tissue varies as a function of the local electric field, leading to a redistribution of the field. These dynamic impedance changes, which depend on the tissue type and the applied electric field, need to be quantified a priori, making mathematical modeling complicated. Here, it is shown that the impedance changes during high-frequency, bipolar electroporation therapy are reduced, and the electric field distribution can be approximated using the analytical solution to Laplace's equation that is valid for a homogeneous medium of constant conductivity. METHODS: Two methods were used to examine the agreement between the analytical solution to Laplace's equation and the electric fields generated by 100 us unipolar pulses and bursts of 1 us bipolar pulses. First, pulses were applied to potato tuber tissue while an infrared camera was used to monitor the temperature distribution in real-time as a corollary to the electric field distribution. The analytical solution was overlaid on the thermal images for a qualitative assessment of the electric fields. Second, potato ablations were performed and the lesion size was measured along the x- and y-axes. These values were compared to the analytical solution to quantify its ability to predict treatment outcomes. To analyze the dynamic impedance changes due to electroporation at different frequencies, electrical impedance measurements (1 Hz to 1 MHz) were made before and after the treatment of potato tissue. RESULTS: For high-frequency bipolar burst treatment, the thermal images closely mirrored the constant electric field contours. The potato tissue lesions differed from the analytical solution by 39.7 +/- 1.3 % (x-axis) and 6.87 +/- 6.26 % (y-axis) for conventional unipolar pulses, and 15.46 +/- 1.37 % (x-axis) and 3.63 +/- 5.9 % (y axis) for high- frequency bipolar pulses. CONCLUSIONS: The electric field distributions due to high-frequency, bipolar electroporation pulses can be closely approximated with the homogeneous analytical solution. This paves way for modeling fields without prior characterization of non-linear tissue properties, and thereby simplifying electroporation procedures. PMID- 26355871 TI - Cation-Dependent Stabilization of Electrogenerated Naphthalene Diimide Dianions in Porous Polymer Thin Films and Their Application to Electrical Energy Storage. AB - Porous polymer networks (PPNs) are attractive materials for capacitive energy storage because they offer high surface areas for increased double-layer capacitance, open structures for rapid ion transport, and redox-active moieties that enable faradaic (pseudocapacitive) energy storage. Here we demonstrate a new attractive feature of PPNs--the ability of their reduced forms (radical anions and dianions) to interact with small radii cations through synergistic interactions arising from densely packed redox-active groups, only when prepared as thin films. When naphthalene diimides (NDIs) are incorporated into PPN films, the carbonyl groups of adjacent, electrochemically generated, NDI radical anions and dianions bind strongly to K(+), Li(+), and Mg(2+), shifting the formal potentials of NDI's second reduction by 120 and 460 mV for K(+) and Li(+)-based electrolytes, respectively. In the case of Mg(2+), NDI's two redox waves coalesce into a single two-electron process with shifts of 240 and 710 mV, for the first and second reductions, respectively, increasing the energy density by over 20 % without changing the polymer backbone. In contrast, the formal reduction potentials of NDI derivatives in solution are identical for each electrolyte, and this effect has not been reported for NDI previously. This study illustrates the profound influence of the solid-state structure of a polymer on its electrochemical response, which does not simply reflect the solution-phase redox behavior of its monomers. PMID- 26355872 TI - Two different motor systems are needed to generate human speech. AB - Vocalizations such as mews and cries in cats or crying and laughter in humans are examples of expression of emotions. These vocalizations are generated by the emotional motor system, in which the mesencephalic periaqueductal gray (PAG) plays a central role, as demonstrated by the fact that lesions in the PAG lead to complete mutism in cats, monkeys, as well as in humans. The PAG receives strong projections from higher limbic regions and from the anterior cingulate, insula, and orbitofrontal cortical areas. In turn, the PAG has strong access to the caudal medullary nucleus retroambiguus (NRA). The NRA is the only cell group that has direct access to the motoneurons involved in vocalization, i.e., the motoneuronal cell groups innervating soft palate, pharynx, and larynx as well as diaphragm, intercostal, abdominal, and pelvic floor muscles. Together they determine the intraabdominal, intrathoracic, and subglottic pressure, control of which is necessary for generating vocalization. Only humans can speak, because, via the lateral component of the volitional or somatic motor system, they are able to modulate vocalization into words and sentences. For this modulation they use their motor cortex, which, via its corticobulbar fibers, has direct access to the motoneurons innervating the muscles of face, mouth, tongue, larynx, and pharynx. In conclusion, humans generate speech by activating two motor systems. They generate vocalization by activating the prefrontal-PAG-NRA-motoneuronal pathway, and, at the same time, they modulate this vocalization into words and sentences by activating the corticobulbar fibers to the face, mouth, tongue, larynx, and pharynx motoneurons. PMID- 26355874 TI - Omitted Acknowledgment. PMID- 26355875 TI - Rejoinder to "Reader reaction: A note on the evaluation of group testing algorithms in the presence of misclassification". PMID- 26355873 TI - The Role of MicroRNA in Hepatitis C Virus Replication. AB - Hepatitis C virus (HCV) infection is a major global health problem. There is no effective vaccine and the current treatment regimen with pegylated interferon alpha and ribavirin is associated with significant adverse events. Therefore, there is an urgent need to identify new antiviral targets for HCV therapy. In recent years, a growing number of microRNAs (miRNAs) have been reported to be able to regulate HCV replication and infection by interacting with the HCV genome directly or by regulating host innate immunity to build a nonspecific antiviral state within cells. In this review, we discuss HCV virology and standard of care followed by miRNA in general, and then give a brief overview of miRNAs involved in HCV infection and discuss their potential application as a therapeutic option for the treatment of HCV infection. PMID- 26355876 TI - A meta-analytic review of the Bethesda System for Reporting Thyroid Cytopathology: Has the rate of malignancy in indeterminate lesions been underestimated? AB - BACKGROUND: The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) provides a 6-tier diagnostic framework using uniform criteria in reports of thyroid aspirates. One of the major advantages of this framework is its association with defined risks of malignancy, allowing standardized management algorithms for each diagnosis. The objective of the current meta-analysis was to demonstrate the feasibility of using TBSRTC among specimens in the atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS) and follicular neoplasm or suspicious for neoplasm (FN/SFN) categories. The authors also evaluated both the morphologic features and the risk of malignancy in the presence of Hurthle cells. METHODS: A literature search was performed of the PubMed, Scopus, and Web of Science databases for English language studies published from January 2008 to December2014. Studies were considered eligible only if they evaluated the risk of malignancy for specimens in the AUS/FLUS and/or FN/SFN categories and included surgical follow-up. RESULTS: In total, 51 articles were identified that used TBSRTC criteria and provided data for a total of 145,928 fine-needle aspiration (FNA) specimens. Of these, FNAs that had surgical follow-up were selected among the AUS/FLUS (N = 4475) and FN/SFN (N = 3202) specimens. The overall rate of malignancy was 27% for the AUS/FLUS category and 31% for the FN/SFN category. CONCLUSIONS: The AUS category was characterized by limited reported follow-up and surgical outcome. The data demonstrated that FNAs with an AUS diagnosis had a higher risk of malignancy than the risk according to published TBSRTC criteria, whereas the percentage of malignancy in FNAs with an FN/SFN diagnosis did not differ from that according to TBSRTC. Hurthle cell lesions represent a challenging category, underlying the importance of further studies to define whether they can be diagnosed in the AUS/FLUS category rather than the FN/SFN category. PMID- 26355877 TI - The influence of display modalities on proximal caries detection and treatment decision. AB - The aim of this study was to investigate the influence of digital radiographic display on caries detection and choice of treatment among undergraduate students. Forty images of extracted human teeth were acquired using a PSP digital system. The proximal surfaces were evaluated for the presence of proximal caries and choice of treatment by 36 undergraduate students, divided into three groups according to the semester they were taking. The images were evaluated in two forms of image display: laptop, and printed on acetate viewed on a lightbox. The accuracy of the different forms of image display on caries detection was evaluated by means of ROC curve analysis and its effect by mixed linear regression. Residue analysis was used to verify the adequacy of the treatment of choice for the chosen diagnosis. There was no significant effect either for the display modalities (p=0.058) or for the different undergraduate student groups (p=0.991). The Az was 0.539 for printed images and 0.516 for laptop. The decisions based on treatment of choice were consistent with the scores achieved for caries detection. Accuracy of caries detection using a laptop was comparable to accuracy using printed images. Treatment decision was not affected by image display modality. The semester of the dentistry course that undergraduate students were taking did not significantly increase the accuracy of their proximal caries detection. PMID- 26355878 TI - A retrospective analysis of reactive hyperplastic lesions of the oral cavity: study of 1149 cases diagnosed between 2000 and 2011, Chile. AB - The aim of this study was to determine the relative frequency and distribution of reactive hyperplastic lesions (RHL) of the oral mucosa at the Oral Pathology Institute of the School of Dentistry at the University of Chile. This was a retrospective study of 1149 biopsies with histopathological diagnosis of RHL, performed between 2000 and 2011. The RHL were classified in 4 groups: fibrous hyperplasia (FH), pyogenic granuloma (PG), peripheral giant-cell granuloma (PGCG) and peripheral ossifying fibroma (POF). RESULTS: the most frequent RHL was FH (71. 1%), followed by PG (21.1%), PGCG (5 %) and POF (2.9%). RHLs were more frequent in women (70.7%). The most highly affected age group was the 50- to 59 year-olds (22%). The most frequent location for RHL was maxilla (24.7%), followed by cheek (20.6%), tongue (19.4%) and jaw (18.5%). The most prevalent RHL diagnosis was FH. The most frequently affected sex was female, the most frequent age range was 50-59 years, and the most frequent location, maxilla. PMID- 26355879 TI - Patients' perception of installation, use and results of orthodontic mini implants. AB - The purpose of this study was to evaluate patient acceptance and perception of pain with regard to orthodontic mini-implants. The study was conducted on 58 individuals undergoing orthodontic treatment, who had orthodontic mini-implants placed as anchorage devices. Data were collected using a questionnaire containing 6 questions evaluating perception of pain during mini-implant placement and during use, difficulty with cleaning, unaesthetic appearance, difficulty with eating and benefits observed. Data were tabulated and analyzed using Fisher and Spearman's Correlation Coefficient tests. It was found that 94.8% of the patients reported that they would be willing to undergo treatment with mini-implants again. Of the negative aspects evaluated, the most significant was discomfort during placement, while the least significant was difficulty with eating. Patients' perception of aspects related to mini-implants was shown to be independent of the quantity of these devices placed. Although the patients evaluated some aspects of mini-implants negatively, the mean score for benefits observed was very high, indicating good patient satisfaction with treatment. PMID- 26355880 TI - Evaluation of two human dental pulp stem cell cryopreservation methods. AB - Dental pulp is a promising source of mesenchymal stem cells for use in cell therapy and regenerative medicine. Methods for storing stem cells with minimum compromise of cell viability, differentiation capacity and function should be developed for clinical and research applications. The aim of this study was to evaluate whether human dental pulp stem cells (hDPSCs) isolated and cryopreserved for 1, 7 and 30 days maintain viability and expression of specific stem cell markers. Human dental pulp stem cells were isolated from 23 healthy patients aged 18 to 31 years. Dental pulp was enzymatically dissociated, and CD105+ cells were separated using the MiltenyiTM system. The hDPSCs were cryopreserved using the Kamath and Papaccio methods. Post-cryopreservation viability was measured by flow cytometry (7AAD) and by the expression of the phenotype markers CD105+/ CD73+, CD34-/CD45-. The Papaccio method showed greater cell viability for cells that had been frozen for 30 days (59.5%) than the Kamath method (56.2%), while the Kamath method provided better results for 1 day (65.5%) and 7 days (56%). Post cryopreservation expression of the markers CD105+/CD34- was greater after 1 and 7 days with the Kamath method and CD105+/CD45- were expressed after all 3 cryopreservation times. There was greater expression of CD73+ in the hDPSCs after 1 and 7 days with the Kamath method, and after 30 days with the Papaccio method. These results suggest that hDPSCs express mesenchymal stem cell markers after cryopreservation. However, cryopreservation time may affect marker expression, probably by altering the spatialconfiguration of cell membrane proteins or by compromising cells at a certain level of differentiation. PMID- 26355881 TI - Subgingivally applied minocycline microgranules in subjects with chronic periodontitis: A randomized clinical and microbiological trial. AB - The aim of this study was to evaluate clinical and microbiological effects of subgingival minocycline microgranules when used as an adjunct to scaling and root planing in subjects with Chronic periodontitis. Twenty-six non-smoker volunteers participated in the study. Four opposite sites, clinically standardized, with bleeding on probing (BOP) and pocket depth (PD) >= 6 mm were selected. Baseline BOP, PD and Clinical attachment level (CAL) were measured and microbiological samples were collected from the study sites and analyzed using PCR. Porphyromonas gingivalis (Pg) Tannerella forsythia (Tf), Treponema denticola (Td) and Aggregatibacter actinomycetemcomitans (Aa) were detected. One side of the mouth was randomly allocated to the experimental treatment: scaling and root planing plus minocycline microgranules (Test group=T) and the other side of the mouth to scaling and root planing alone (Control group=C). At days 30 and 90, clinical and microbiological examination was repeated. After 30 days BOP was reduced to 81% in C and to 12% in T and at day 90 to 58% in C and to 8% in T (p<0.05). PD was significantly reduced in both groups (C: 4.8mm, T: 4.2mm) favoring T at days 30 and 90 (p<0.05). CAL reduction at day 30 showed no difference between groups. At day 90, CAL reduction was higher in T (p<0.05). At days 30 and 90 Pg, Tf, Td and Aa was reduced in both groups. Pg reduction was significantly greater in group T. At day 90 frequency of sites with Td decreased in T and increased in C (p<0.05). No adverse effect was observed. This study showed that minocycline microgranules adjunct to scaling and root planing resulted in grater reduction of BOP and PD, higher CAL gain, increased probability of Pg suppression and retarded recolonization of Td than root instrumentation alone. PMID- 26355882 TI - Ex vivo microleakage comparison between glass ionomers used as pit and fissure sealants. AB - The aim of this study was to evaluate in vitro the marginal microleakage of two glass ionomer materials used as pit and fissure sealants. Thirty healthy premolars extracted for orthodontic treatment were randomly assigned to two groups (n=15) and respectively sealed with two glass ionomers (Group I, Fuji VII and Group II, Fuji IX). All teeth were preserved in artificial saliva (NAF) for 10 days, thermocycled (250 cycles; 5 degrees C, 37 degrees C and 60 degrees C), isolated, and immersed in 2% alcohol gentian violet blue solution for 24 h. After washing, teeth were included in acrylic resin and sectioned longitudinally in a bucco-lingual direction with a Struers-Minitom cutting device. Samples were analyzed for leakage using an optical microscope (Olympus BX- 60M). TheWilliams and Winter semi-quantitative ranked scale was used to score dye penetration. In Group I the grades were distributed as follows: Grade 1, 1 sample and Grade 3, 14 samples (Mean 2.87 Median 3, SD 0.52). In Group II: Grade 0: 4 samples, Grade 1, 3 samples, Grade 2, 2 samples and Grade 3, 6 samples (Mean 1.67, Median 2, SD 1.29). Fisher's exact test showed statistically significant differences between materials (p=0.006). From these results, we conclude that Fuji IX had better marginal sealing than Fuji VII when used as a pit and fissure sealant. PMID- 26355883 TI - Changes in pH of irrigating solutions after contact with human root dentin. AB - The aim of this study was to analyze the in vitro behavior of the pH of different irrigating solutions, used alone or consecutively, after contact with extracted human teeth. Mandibular human premolars were selected. The middle thirds were divided into 6 parts. The specimens obtained were divided into 6 groups and treated with irrigating solutions: 1) distilled water; 2) 1% NaOCl; 3) 1% Citric Acid (CA); 4) 17% EDTA; 5) 1% CA + 1% NaOCl; 6) 17% EDTA + 1% NaOCl. Specimens were immersed in 1 mL of each solution at 37oC, those of groups 1, 2, 3 and 4, for 5 minutes, and the rest, consecutively for 2.5 minutes in each solution. Initial and final pH of the solutions were determined. Data were analyzed by the T Test, one-way analysis of variance (ANOVA) and Tukey multiple comparison Test. At 2.5 and 5 minutes there were significant differences between the initial and final pH for all solutions. The pH values decreased for distilled water and NaOCl, while they increased for CA and EDTA. In vitro, the pH of all solutions was modified after contact with root dentin at both test times (2.5 and 5 min). PMID- 26355884 TI - A laboratory assessment of bacterial leakage in MTA apical plugs exposed to phosphate-buffered saline. AB - This study evaluated the influence of the exposure of mineral trioxide aggregate (MTA) - with and without calcium chloride (CaCl2) -to phosphate-buffered saline (PBS) on apical microleakage. Sixty root segments were divided into 4 experimental groups (n=15). Apical cavities were filled with MTA with or without CaCl2, and the root canals dressed with a moistened cotton pellet or PBS: 1) MTA/cotton pellet; 2) MTA/PBS; 3) MTA+ 10%CaCl2/cotton pellet; 4) MTA+10%CaCl2/PBS. After 2 months, E. faecalis penetration was analyzed along the apical plugs. Samples were observed weekly for 70 days, and leakage was detected by turbidity of the medium in contact with the root segment. Teeth in the control groups (n=2) were either made completely impermeable or kept without an apical plug. The Kaplan-Meier method was used to analyze survival and the Logrank test was used to compare the survival curves (p<0.05). All specimens in the positive control group showed evidence of leakage within 24h, while none in the negative control group showed leakage up to 70 days. There was no statistically significant difference among the experimental groups (p=0.102). The use of PBS as intracanal dressing may improve MTA sealing ability, but cannot prevent bacterial leakage. The addition of CaCl2 to the MTA did not improve MTA sealing ability. PMID- 26355885 TI - Edentulism and dental prostheses in the elderly: impact on quality of life measured with EuroQol--visual analog scale (EQ-VAS). AB - The objective of this study was to measure the impact of edentulism and dental prostheses on quality of life (QOL) in older adults in Bogota, Colombia. Edentulism is a frequent condition in older adults and has great impact on their QOL. No epidemiological data are currently available on edentulism among older adults in Colombia. Data were obtained from the SABE-Bogota study, a cross sectional study conducted in 2012, and used to analyze the EQ-VAS (Visual Analog Scale) from the EuroQol instrument to measure the perception of quality of life (QOL) in relation to edentulism. The study included 2,000 individuals over 60 years old. The Spearman-Rho correlation was used to analyze the correlation between EQ-VAS and edentulism. Chi-Square, ANOVA and t-test were used to study the differences in EQ-VAS scores between edentulous and healthy subjects. Statistical significance was set at p<0.05. Of the 2000 respondents, 98.3% were edentulous, 73.0% reported half or more missing teeth, 76.9% used dental prostheses and 23.7% had related eating problems. Older age, lower social class and lower education were related to edentulism. Individuals with fewer teeth and dental prostheses had lower EQ-VAS scores (p<0.05) and dental prosthesis did not improve EQ-VAS scores (p=0.22). Edentulism also showed a significant negative correlation with EQ-VAS scores (rho= -0.102, p<0.01). In summary, EQ-VAS is a useful tool for measuring the perception of QOL in dental health scenarios. Edentulism significantly affects QOL in older adults and the use of dental prosthesis does not improve the perception of QOL. PMID- 26355886 TI - Influence of alginate impression materials and storage time on surface detail reproduction and dimensional accuracy of stone models. AB - This study compared the surface detail reproduction and dimensional accuracy of stone models obtained from molds prepared using different alginate impression materials (Cavex ColorChange, Hydrogum 5, or Jeltrate Plus) and with different storage times (1, 3, and 5 days) to models from molds that were filled immediately with no storage time. The molds were prepared over a matrix containing 50-MUm line, (ISO 1563 standard) under pressure with a perforated metal tray. The molds were removed 2 minutes after loss of sticky consistency and either filled immediately or stored in closed jars at 100% relative humidity and 37 degrees C for 1, 3, or 5 days. The molds were filled with dental plaster (Durone IV). Surface detail reproduction and dimensional accuracy were evaluated using optical microscopy on the 50-MUm wide line, which was 25 mm in length, according to ISO 1563 standard. The dimensional accuracy results (%) were subjected to analysis of variance. The 50-MUm wide line (ISO 1563 standard) was completely reproduced by all alginate impression materials regardless of the storage time. There was no statistically significant difference in the mean dimensional accuracy values of stone models made from molds composed of different alginate impression materials and with different storage times (p = 0.989). In conclusion, storing the mold for five days prior to filling did not change the surface detail reproduction or dimensional accuracy of the alginates examined in this study. PMID- 26355887 TI - Correlation between gingival thickness and gingival recession in humans. AB - Gingival recession is characterized by the apical migration of the gingival margin, exposing the root surface. Studies have demonstrated several etiological factors for gingival recession such as periodontitis, traumatic toothbrushing, use of oral piercing, and past orthodontic therapy, among others. It might not be possible to identify and quantify the influence of each factor, and gingival recession at some sites may be the result of the combination of these factors. Gingival recession affects individuals at all ages, with prevalence increasing as time passes. The aim of this study was to observe whether there is correlation between gingival thickness and gingival recession. Fifty-five subjects of both genders aged 18-35 years participated in the study. The volunteers were under treatment at the School of Dentistry of the Federal University of Rio Grande do Sul. Buccal gingival thickness was measured on incisors, canines and bicuspids, under anesthesia, following inclusion and exclusion criteria. Statistical analysis was performed with STATA version 10.1. The results had a Pearson Correlation Coefficient of -0.216. Linear regression had a statistically significant pvalue of 0.025. It may be concluded that there is weak negative correlation between gingival thickness and gingival recession. PMID- 26355888 TI - The concentration of il-1beta in saliva of children with oral lesions associated to histiocytosis. AB - Langerhans Cell Histiocytosis (LCH) is a disease whose etiology and pathogenesis are still unknown. It affects several organs and tissues, producing lesions of different severity. Its histopathology and clinical picture suggest the participation of cytokines in its pathogenesis. IL-1beta might have an important role in its development. The purpose of this study was to determine the concentrations of IL-1beta in saliva of pediatric patients diagnosed with LCH, with and without oral manifestations (Groups 1 and 2 respectively) compared to a Control Group (Group 3) of pediatric patients without medical antecedents or oral lesions. The saliva of twenty patients with LCH was studied and compared to a Control Group consisting of eleven pediatric patients without medical antecedents. The children with histiocytosis, aged four months to sixteen years, were referred by the Oncohaematology Service at Garrahan Hospital and Hospital de Clinicas, to the Department of Comprehensive Children's Dentistry, School of Dentistry, University of Buenos Aires (UBA). The concentrations of IL-1beta in the different groups were determined using the Enzyme Immune Assay Kit (Cayman MI, USA) and expressed in pg/ml. Results were analyzed by the Kruskall Wallis test. Significant differences between the three cohorts were found, (H = 20.36, P < 0.001). Dunn's multiple comparison analysis was performed, which showed significant differences between Groups 1 and 2, and between Groups 1 and 3 (P < 0.05). Higher values of IL-1beta were found in the patients with histiocytosis with oral manifestations (Group 1) than in patients without manifestations (Group 2) and patients in the Control Group (Group 3). PMID- 26355889 TI - An experimental model of disuse in the alveolar rat bone: A histomorphometrical study. AB - Lack of mechanical stimulation is known to cause disuse osteopenia in bones. However, experimental models for disuse osteopenia on bones other than jawbones are not applicable to jawbones. The little available information in this field has been applied to the study of overeruption of teeth lacking antagonists. However, the absence of an antagonist in the opposite jaw means that there is no stimulation by occlusion. Our hypothesis is that the lack of stimulation due to the absence of teeth causes disuse osteopenia in the interradicular bone of the antagonist teeth. Our aim was to develop a model of disuse osteopenia due to the absence of occlusal forces. We used male Wistar rats with 215-230 g body weight, divided into 2 groups: one absolute control group (C) and one experimental group in which the three right lower molars were extracted (E). The left side of the jaw in the experimental group was used as a paired control (PC). The animals were euthanized 7 days after extraction. The jaws were placed in occlusion, fastened and fixed in 10% formalin. The heads were cut in half and radiographs made of both jaws. The upper jaws were processed histologically. After decalcification, bucco-palatine oriented sections were cut at the level of the mesial root and distal roots of the first upper molars. On the radiographs, the distance from the tip of the cusp on the first upper molar to the antagonist edentulous ridge (DA) was measured. On the microphotographs, the following parameters were measured: passive eruption degree (PED), height of periodontal ligament at the level of the furcation (HPL) and interradicular bone volume (BVI). The data were compared statistically using ANOVA and Bonferroni's post-hoc test, considering p<0.05 as statistically significant. DA in experimental animals was 0.34?}0.048 mm. PED in experimental animals was significantly greater than in the control groups, both for the buccal plate and for the palatal plate. HPL showed no significant difference between groups. BVI was significantly lower in the experimental group than in the control group. The results showed that the model used produces a condition of disuse osteopenia, shown by the statistically significant reduction in interradicular bone volume. The use of this model at different experimental times will enable the evaluation of cell responses in periodontal tissues, particularly bone tissue, e.g. to compare them to known responses such as the application of orthodontic forces. PMID- 26355890 TI - Antiseptic mouthwashes: in vitro antibacterial activity. AB - Mouthwashes are used as an adjunct to tooth brushing for improving breath and preventing oral diseases. The aim of this study was to compare the in vitro Maximum Inhibitory Dilution (MID) of 3 mouthwashes with different active ingredients against mutans streptococci (MS). The products analyzed were Periogard(r), Cepacol(r) and Plax(r) Fresh Mint. Their antibacterial activity was assessed in duplicate in 96-well microtiter plates against 36 clinical isolates of MS. Each mouthwash was submitted to a serial two-fold dilution (1/2.5 to 1/5120) using double concentration of Tryptose Soy Broth with 1.0% yeast extract. The final volume in each well was 100 mL plus 5 mL of a bacterial suspension, equivalent to 107 CFU/mL. They were incubated microaerobically at 37 degrees C for 48 hours and the MIDs determined. MID was 1/320 for Periogard(r) and Cepacol(r), and 1/20 for PlaxR(r) Statistical analysis revealed that the MID of Periogard(r) MID did not differ from that of Cepacol(r) (p>0.05), and was higher than that of Plax(r) (p<0.05). In conclusion, the antiseptic mouthwashes containing chlorhexidine (Periogard(r)) and cetylpyridinium chloride (Cepacol(r)) had higher in vitroantibacterial activity (MID) against MS than the antiseptic mouthwash containing triclosan (Plax(r)), according to microbiological method employed. PMID- 26355891 TI - Association among salivary flow rate, caries risk and nutritional status in pre schoolers. AB - Modeer T. et al.(2011) claim that there is association between decreased salivary flow rate and caries in obese adolescents. The aim of this study was to determine the association among nutritional status, salivary flow rate and caries risk in preschoolers. The study comprised 60 children aged 3 to 6 years attending kindergartens in areas immediately adjacent to Buenos Aires City, Argentina. Body weight and height of the children were determined. Body mass index was calculated and the population was classified anthropometrically according to the WHO 2007 (WHO Anthro. Program). Caries risk was determined. Saliva was collected in sterile graduated widemouth containers, without stimulation and without food restrictions. Salivary flow rate (SFR) was determined. Statistical analysis was performed using Pearson's test. It was found that 56.7% (IC95%: 37.7-74.0) of anthropometrically adequate children (Ad) and 37.0% (IC95%: 20.1-57.5) of overweight and obese children (OW/Ob) had caries. The odds ratio for caries (OR=3.78; IC95%: 1.2-11.8, p=0.02) was almost 4 times higher in adequate children than in the others. SFR was 0.534 0.318 ml/min in Ad and 0.439 ?} 0.234 ml/min in OW/Ob. Pearson's test showed no correlation between SFR and nutritional status (r= 0.004592, p= 0.5977). Although the presence of caries was lower in overweight and obese children, no correlation was found between nutritional status and salivary flow rate. PMID- 26355892 TI - Ultrastructure of the surface of dental enamel with molar incisor hypomineralization (MIH) with and without acid etching. AB - The aim of the present work was to analyze the ultrastructure and mineral composition of the surface of the enamel on a molar with MIH, with and without acid etching. A permanent tooth without clinical MIH lesions (control) and a tooth with clinical diagnosis of mild and moderate MIH, with indication for extraction, were processed with and without acid etching (H3PO4 37%, 20") for observation with scanning electron microscope (SEM) ZEISS (Supra 40) and mineral composition analysis with an EDS detector (Oxford Instruments). The control enamel showed normal prismatic surface and etching pattern. The clinically healthy enamel on the tooth with MIH revealed partial loss of prismatic pattern. The mild lesion was porous with occasional cracks. The moderate lesion was more porous, with larger cracks and many scales. The mineral composition of the affected surfaces had lower Ca and P content and higher O and C. On the tooth with MIH, even on normal looking enamel, the demineralization does not correspond to an etching pattern, and exhibits exposure of crystals with rods with rounded ends and less demineralization in the inter-prismatic spaces. Acid etching increased the presence of cracks and deep pores in the adamantine structure of the enamel with lesion. In moderate lesions, the mineral composition had higher content of Ca, P and Cl. Enamel with MIH, even on clinically intact adamantine surfaces, shows severe alterations in the ultrastructure and changes in ionic composition, which affect the acid etching pattern and may interfere with adhesion. PMID- 26355893 TI - Alternate PAX3-FOXO1 oncogenic fusion in biphenotypic sinonasal sarcoma. AB - Biphenotypic sinonasal sarcoma (SNS) is a low grade spindle cell sarcoma that affects middle-aged adults, in which the PAX3-MAML3 chimeric transcription factor induces an aberrant dual myogenic and neuroectodermal phenotype. We report an alternate PAX3-FOXO1 oncogenic fusion in SNS, confirming the crucial role of PAX3 in SNS oncogenesis. The presence of PAX3-FOXO1 in SNS and alveolar rhabdomyosarcoma suggests that these two entities are genetically similar lesions arising from distinct progenitor cell pools. This finding has important implications for the molecular diagnosis of SNS and alveolar rhabdomyosarcoma, and underscores the critical contribution of the cell of origin to the phenotype induced by oncogenic transcription factor reprogramming. PMID- 26355894 TI - High glucose inhibits ClC-2 chloride channels and attenuates cell migration of rat keratinocytes. AB - BACKGROUND: Accumulating evidence has demonstrated that migration of keratinocytes is critical to wound epithelialization, and defects of this function result in chronic delayed-healing wounds in diabetes mellitus patients, and the migration has been proved to be associated with volume-activated chloride channels. The aim of the study is to investigate the effects of high glucose (HG, 25 mM) on ClC-2 chloride channels and cell migration of keratinocytes. METHODS: Newborn Sprague Dawley rats were used to isolate and culture the keratinocyte in this study. Immunofluorescence assay, real-time polymerase chain reaction, and Western blot assay were used to examine the expression of ClC-2 protein or mRNA. Scratch wound assay was used to measure the migratory ability of keratinocytes. Transwell cell migration assay was used to measure the invasion and migration of keratinocytes. Recombinant lentivirus vectors were established and transducted to keratinocytes. Whole-cell patch clamp was used to perform the electrophysiological studies. RESULTS: We found that the expression of ClC-2 was significantly inhibited when keratinocytes were exposed to a HG (25 mM) medium, accompanied by the decline of volume-activated Cl(-) current (I Cl,vol), migration potential, and phosphorylated PI3K as compared to control group. When knockdown of ClC-2 by RNAi or pretreatment with wortmannin, similar results were observed, including I Cl,vol and migration keratinocytes were inhibited. CONCLUSION: Our study proved that HG inhibited ClC-2 chloride channels and attenuated cell migration of rat keratinocytes via inhibiting PI3K signaling. PMID- 26355895 TI - Postpartum smoking relapse--a thematic synthesis of qualitative studies. AB - BACKGROUND AND AIMS: Many women quit smoking during pregnancy, but relapse after the baby is born. To understand why and identify ways of preventing this, this study reviewed the qualitative literature on women's experience of postpartum smoking relapse. METHODS: A systematic review of qualitative studies and process evaluations of trials. We undertook a thematic synthesis of published qualitative data. RESULTS: We screened 1336 papers. Twenty-two papers reporting on 16 studies were included, reporting on the views of 1031 postpartum women. Factors affecting relapse and barriers and facilitators to relapse prevention were identified around the key themes of beliefs, social influences, motivation, physiological factors and identity. Women's beliefs about smoking as a means of coping with stress and the need for social support, especially from a partner, emerged as important. Extrinsic motivation to quit during the pregnancy (for the health of the fetus) appeared to be a factor in prompting relapse after the baby was born. During the immediate postpartum period women believed that physiological changes influence cigarette cravings. The stress of caring for a newborn, sleeplessness and adjusting to a new mothering identity were also reported to be important. CONCLUSIONS: Among women who quit smoking during pregnancy, those who relapse postpartum talk commonly about no longer needing to protect the baby and the effects of stress. Partner support and a sense of changed identity are cited as factors preventing relapse. PMID- 26355897 TI - Increased risk of severe infections in cancer patients treated with vascular endothelial growth factor receptor tyrosine kinase inhibitors: a meta-analysis. AB - BACKGROUND: Vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) have been widely used in a variety of solid malignancies. Concerns have arisen regarding the risk of severe infections (>=grade 3) with use of these drugs, but the contribution of VEGFR-TKIs to infections is still unknown. METHODS: The databases of PubMed and abstracts presented at oncology conferences' proceedings were searched for relevant studies from January 2000 to December 2014. Summary incidences, Peto odds ratio (Peto OR), and 95% confidence intervals (CIs) were calculated by using either random-effects or fixed-effects models according to the heterogeneity of included studies. RESULTS: A total of 16,488 patients from 27 randomized controlled trials were included. The risk of developing severe (Peto OR 1.69, 95% CI: 1.45-1.96, P<0.001) and fatal infections (Peto OR 1.78, 95% CI: 1.13-2.81, P=0.013) was significantly increased in patients treated with VEGFR-TKIs when compared to controls. Exploratory subgroup analysis showed no effect of tumor types, phase of trials, or agent used on the Peto OR of severe infections. When stratified according to specific infectious events, the risks of high-grade febrile neutropenia, pneumonia, fever, and sepsis were increased compared with controls, with Peto ORs of 1.57 (95% CI: 1.30-1.88, P<0.001), 1.79 (95% CI: 1.29-2.49, P<0.001), 5.35 (95% CI: 1.47-19.51, P=0.011), and 3.68 (95% CI: 1.51-8.99, P=0.004), respectively. Additionally, VEGFR-TKIs significantly increased the risk of fatal sepsis (OR 3.66, 95% CI: 1.47-9.13, P=0.005) but not fatal pneumonia (OR 1.34, 95% CI: 0.80-2.25, P=0.26). CONCLUSION: The use of VEGFR-TKIs significantly increases the risk of developing severe and fatal infectious events in cancer patients. A close monitoring for any signs of infections is recommended for patients treated with VEGFR-TKIs. PMID- 26355906 TI - Toward colorectal cancer control in Africa. PMID- 26355907 TI - Surface roughness of dental implants and treatment time using six different implantoplasty procedures. AB - OBJECTIVES: To test whether or not one of six implantoplasty procedures is superior to the others rendering a minimal final implant surface roughness and a short treatment time. MATERIAL AND METHODS: Forty-two one-piece implants were embedded in epoxy resin blocks with 6-mm rough implant surface exposed. The following implantoplasty polishing sequences were applied: Brownie((r)) , Greenie((r)) sequence (BG) (diamond rotary instruments 106-, 40-, 15-MUm grit, Brownie((r)) , Greenie((r)) silicone polishers); Arkansas stone sequence (AS) (diamond 106-, 40-, 15-MUm grit, Arkansas stone torpedo-shaped bur); Short diamond sequence (SD) (diamond 106-, 40-, 4-MUm grit); Short diamond sequence with Greenie((r)) (SDG) (diamond 106-, 40-, 4-MUm grit, Greenie((r)) ); Complete diamond sequence (CD) (diamond 106-, 40-, 15-, 8-, 4-MUm grit); Complete diamond sequence with Greenie((r)) (CDG) (106-, 40-, 15-, 8-, 4-MUm grit, Greenie((r)) ). The polished neck portion served as a positive control, the untreated sandblasted and acid-etched surface as negative control. Each implant was scanned with a contact profilometer rendering Ra values and Rz values as a measure of surface roughness. The time needed to polish the implant surface for each group was recorded. Simultaneous comparisons between more than two groups were done performing Kruskal-Wallis tests. Comparisons between two groups were analysed using Wilcoxon rank-sum tests. RESULTS: Mean Ra values amounted to 0.32 +/- 0.14 MUm (BG), 0.39 +/- 0.13 MUm (AS), 0.59 +/- 0.19 MUm (SDG), 0.71 +/- 0.22 MUm (SD), 0.75 +/- 0.26 MUm (CDG), 0.98 +/- 0.30 MUm (CD), 0.10 +/- 0.01 MUm (PC) and 1.94 +/- 0.47 MUm (NC). Pairwise one-sided comparisons between the test group revealed statistically significant differences (P < 0.05). The shortest treatment time was recorded for group AS (13 +/- 2 min) and the longest for CDG (21 +/- 2 min) and BG (21 +/- 4 min). CONCLUSIONS: Considering final surface roughness and treatment duration, the use of rotary diamond burs in decreasing roughness, followed by an arkansas stone (group AS), appears to be an optimal treatment option. PMID- 26355908 TI - Genetic alterations in periprosthetic soft-tissue masses from patients with metal on-metal hip replacement. AB - Adverse soft tissue reactions in patients with metal-on-metal (MoM) hip replacement are associated with cobalt (Co) and chromium (Cr) particles released from the implant. Exposing the patients to long periods of increased metal ions concentrations resulting from the wear of these implants poses an increased risk of genotoxicity/mutagenicity. A variable proportion of patients develop periprosthetic soft-tissue masses or pseudotumors at the site of the implant. There is a concern that exposure to increased metal ions could increase the risk of cancer. In order to investigate whether the periprosthetic soft-tissue mass harbours any cancer- related genetic alterations, we studied DNA isolated from periprosthetic tissues of 20 patients with MoM hip replacement, for copy number alterations and mutations in hotspot regions of 50 cancer genes using aCGH and amplicon-based next generation sequencing. Our results showed copy number gains at 12q14.3 and 21q21.1in tumour from patient diagnosed with liposarcoma. Copy number alterations in periprosthetic tissues were seen in three other patients, one had a region of gain at 9q24.1 affecting JAK2 and INSL6, and two patients had region of gain at 6p21.1, affecting RUNX2. Mutation analysis showed V1578del mutation in NOTCH1 in two patients. The copy number alterations and mutations seen in periprosthetic soft-tissue masses are earlier reported in either haematological malignancies or in osteoblast related bone dysplasia. The presence of genetic anomalies was associated with longer in-situ time of the implant. Our findings warrant the need of similar studies in larger patient cohorts to evaluate the risk of development of neoplastic alterations in periprosthetic tissues of patients with MoM hip replacement. PMID- 26355909 TI - Multiple spinal arteriovenous fistulas: A case-based review. AB - The occurrence of multiple spinal dural arteriovenous fistulas (AVFs) is rare. The majority of cases reported are synchronous and the lesions are mainly found at different spinal levels. Metachronous AVFs have been defined as lesions that manifest in a temporal sequence after treatment of a first AVF. In this report, we present two distinct cases of multiple spinal AVFs. Also, we review the main features of the cases previously reported, with emphasis on the proposed theories for the origin of multiple AVFs. In patients with failure to improve after treatment of a spinal DAVF, a whole-spine angiographic examination is mandatory, not only to ascertain the complete closure of the treated fistula, but also to look for a possible second lesion at a different spinal level. PMID- 26355910 TI - Cerebral proliferative angiopathy with papilledema. AB - A young female presented with intermittent blurring of vision and mild to moderate headache for three months. Fundus examination revealed bilateral papilledema with secondary optic atrophy (right more than left). Computed tomography scan of brain showed a diffuse intraparenchymal vascular malformation in right parietooccipital region. Cerebral digital subtraction angiography (DSA) revealed diffuse nidus in right parietooccipital area, supplied by multiple branches of distal middle cerebral artery and anterior cerebral artery. Scattered puddling appearance of contrast was noted in diffuse nidus and there were no definite arterial feeders. DSA was consistent with the diagnosis of cerebral proliferative angiopathy (CPA). The patient was started on acetazolamide 250 mg twice a day. At six months follow up, she was asymptomatic with resolving papilledema. CPA is a rare vascular malformation, any case report that gives further insight to it will be very useful to the scientific community. Herein, we describe an unusual association of CPA with papilledema. PMID- 26355911 TI - Navigating in tissue mazes: chemoattractant interpretation in complex environments. AB - Guided cell movement is essential for development and integrity of animals and crucially involved in cellular immune responses. Leukocytes are professional migratory cells that can navigate through most types of tissues and sense a wide range of directional cues. The responses of these cells to attractants have been mainly explored in tissue culture settings. How leukocytes make directional decisions in situ, within the challenging environment of a tissue maze, is less understood. Here we review recent advances in how leukocytes sense chemical cues in complex tissue settings and make links with paradigms of directed migration in development and Dictyostelium discoideum amoebae. PMID- 26355913 TI - Sustained Improvements in Dynamic Balance and Landing Mechanics After a 6-Week Neuromuscular Training Program in College Women's Basketball Players. AB - CONTEXT: Epidemiological data demonstrate the need for lower-extremity injury prevention training. Neuromuscular-control (NMC) programs are immediately effective at minimizing lower-extremity injury risk and improving sport-related performance measures. Research investigating lasting effects after an injury prevention program is limited. OBJECTIVE: To determine whether dynamic balance, landing mechanics, and hamstring and quadriceps strength could be improved after a 6-wk NMC intervention and maintained for a season. DESIGN: Prospective case series. SETTING: Controlled laboratory. PARTICIPANTS: 11 Division I women's basketball players (age 19.40 +/- 1.35 y, height 178.05 +/- 7.52 cm, mass 72.86 +/- 10.70 kg). INTERVENTIONS: Subjects underwent testing 3 times, completing the Star Excursion Balance Test (SEBT), Landing Error Scoring System (LESS), and isometric strength testing for the hamstrings and quadriceps muscles. Pretest and posttest 1 occurred immediately before and after the intervention, respectively, and posttest 2 at the end of the competitive season, 9 mo after posttest 1. Subjects participated in eighteen 30-min plyometric and NMC-training sessions over a 6-wk period. MAIN OUTCOME MEASURES: The normalized SEBT composite score, normalized peak isometric hamstrings:quadriceps (H:Q) ratio, and the LESS total score. RESULTS: The mean composite reach significantly improved over time (F2,10 = 6.96, P = .005) where both posttest scores were significantly higher than pretest (70.41% +/- 4.08%) (posttest 1 73.48% +/- 4.19%, t10 = -3.11, P = .011) and posttest 2 (74.2% +/- 4.77%, t10 = -3.78, P = .004). LESS scores significantly improved over time (F2,10 = 6.29, P = .009). The pretest LESS score (7.30 +/- 3.40) was higher than posttest 1 (4.9 +/- 1.20, t10 = 2.71, P = .024) and posttest 2 (5.44 +/- 1.83, t10 = 2.58, P = .030). There were no statistically significant differences (P > .05) over time for the H:Q ratio when averaging both legs (F2,10 = 0.83, P = .45). CONCLUSIONS: A 6-wk NMC program improved landing mechanics and dynamic balance over a 9-mo period in women's basketball players. NMC adaptations can be retained without an in-season maintenance program. PMID- 26355914 TI - Interplay of coupling between strain and rotation in ferroelectric SrZrO3/SrTiO3 superlattices. AB - The combination of oxygen octahedral rotation and epitaxial strain provides a unique opportunity to tune the ferroelectric properties of perovskite superlattices. Here, through first-principles calculations, we demonstrate that the oxygen octahedral rotation predominates the ground state and ferroelectric properties of SrZrO3/SrTiO3 superlattices. The predicted ground state combines the ferroelectric distortion and antiferrodistortive modes simultaneously. The structure-strain phase diagrams of the superlattices are calculated with and without octahedral rotations, which elucidate the interplay of coupling between epitaxial strain and octahedral rotation. It is found that the presence of octahedral rotation not only lowers the energy but also changes the sequence of phase transition from c-r-aa to c-r, in which the coupling of rotation and strain induces an out-of-plane polarization that transforms aa-phase into r-phase. PMID- 26355912 TI - Galectins regulate the inflammatory response in airway epithelial cells exposed to microbial neuraminidase by modulating the expression of SOCS1 and RIG1. AB - Influenza patients frequently display increased susceptibility to Streptococcus pneumoniae co-infection and sepsis, the prevalent cause of mortality during influenza pandemics. However, the detailed mechanisms by which an influenza infection predisposes patients to suffer pneumococcal pneumonia are not fully understood. A murine model for influenza infection closely reflects the observations in human patients, since if the animals that have recovered from influenza A virus (IAV) sublethal infection are challenged with S. pneumoniae, they undergo a usually fatal uncontrolled cytokine response. We have previously demonstrated both in vitro and in vivo that the expression and secretion of galectin-1 (Gal1) and galectin-3 (Gal3) are modulated during IAV infection, and that the viral neuraminidase unmasks galactosyl moieties in the airway epithelia. In this study we demonstrate in vitro that the binding of secreted Gal1 and Gal3 to the epithelial cell surface modulates the expression of SOCS1 and RIG1, and activation of ERK, AKT or JAK/STAT1 signaling pathways, leading to a disregulated expression and release of pro-inflammatory cytokines. Our results suggest that the activity of the viral and pneumococcal neuraminidases on the surface of the airway epithelial cells function as a "danger signal" that leads to rapid upregulation of SOCS1 expression to prevent an uncontrolled inflammatory response. The binding of extracellular Gal1 or Gal3 to the galactosyl moieties unmasked on the surface of airway epithelial cells can either "fine-tune" or severely disregulate this process, respectively, the latter potentially leading to hypercytokinemia. PMID- 26355917 TI - Synthesis of well dispersed polymer grafted metal-organic framework nanoparticles. AB - Novel polymer grafted metal-organic framework (MOF) nanoparticles were synthesized. The formed core/shell nanoparticles exhibit outstanding water dispersity and pH sensitivity, and show their catalytic effect for the reduction reaction of 4-nitrophenol (NP) to 4-aminophenol (AP) when loaded with Pd(0) catalyst. PMID- 26355915 TI - Characterization of patients treated by rehabilitation service after establishing of an acute stroke unit in a Brazilian hospital. AB - [Purpose] The study aimed to characterize patients treated by rehabilitation section after establishment of an acute stroke unit. [Subjects and Methods] Medical consultation records of individuals with ischemic stroke were studied retrospectively, excluding individuals with hemorrhagic stroke, thrombolysis, previous Modified Rankin Scale >= 1, prior stroke, structural bone deformities, associated neurological disease, and prior cognitive deficit. The data evaluated were age, gender, etiology, localization, treatment received, ictus onset, hospitalization time, discharge date, and date of first evaluation at the rehabilitation center. The Modified Rankin Scale in 90 days after ictus was utilized to measure functional incapacity with the individuals divided into two groups, before and after acute stroke unit implementation (2010). Functional incapacity was compared between before and after acute stroke unit implementation by the Mann-Whitney test, chi(2) test and Fisher's exact test. [Results] The medical records of 170 patients were evaluated. In the group evaluated after 2010, the patients were significantly older and presented a shorter time between hospitalization and discharge, shorter time until the first evaluation in rehabilitation, and increased percentage of mild incapacity (Modified Rankin Scale = 0 to 2). [Conclusion] After acute stroke unit implementation, the patients treated in the rehabilitation section presented a shorter hospitalization time and rehabilitation delay and less functional incapacity. PMID- 26355916 TI - Identification of Purines and 7-Deazapurines as Potent and Selective Type I Inhibitors of Troponin I-Interacting Kinase (TNNI3K). AB - A series of cardiac troponin I-interacting kinase (TNNI3K) inhibitors arising from 3-((9H-purin-6-yl)amino)-N-methyl-benzenesulfonamide (1) is disclosed along with fundamental structure-function relationships that delineate the role of each element of 1 for TNNI3K recognition. An X-ray structure of 1 bound to TNNI3K confirmed its Type I binding mode and is used to rationalize the structure activity relationship and employed to design potent, selective, and orally bioavailable TNNI3K inhibitors. Identification of the 7-deazapurine heterocycle as a superior template (vs purine) and its elaboration by introduction of C4 benzenesulfonamide and C7- and C8-7-deazapurine substituents produced compounds with substantial improvements in potency (>1000-fold), general kinase selectivity (10-fold improvement), and pharmacokinetic properties (>10-fold increase in poDNAUC). Optimal members of the series have properties suitable for use in in vitro and in vivo experiments aimed at elucidating the role of TNNI3K in cardiac biology and serve as leads for developing novel heart failure medicines. PMID- 26355918 TI - [Results of comprehensive management of patients with chronic lower limb ischaemia using gene-engineering technologies of angiogenesis stimulation (Part 1)]. AB - Presented herein are the results of clinical use of gene engineering methods of stimulating angiogenesis in patients with chronic lower limb ischaemia. An open prospective controlled clinical study included a total of 160 patients with chronic lower limb ischaemia. Gene engineering technologies of angiogenesis stimulation were used both as an independent method of treatment in comprehensive conservative therapy (80 patients) and as comprehensive treatment in combination with revascularizing operations (80 patients). Part One of the article deals with the results outcomes of using the above technologies in combination combined with surgical treatment. It was shown that gene-engineering technologies of angiogenesis stimulation increase efficiency of comprehensive management of patients with lower limb chronic ischaemia of any severity. Additional use of gene-engineering methods of inducing angiogenesis does not virtually change the immediate outcomes of surgical treatment but considerably increase their efficacy in the remote postoperative period and accordingly improves the long-term results of treatment for this cohort of patients. PMID- 26355919 TI - Carotid artery disease in patients with type 2 diabetes. AB - The aim of this study is to determine the risk factors for carotid artery disease (CARD) in patients with type 2 diabetes. 340 pts with T2DM and coronary artery disease were enrolled in cross sectional study. Evaluation for CARD was done by ultrasound. Multivariant logistic regresion analysis defined as independent predictors for CARD: age of occurrence of bilateral plaques, PAD about the presence of bilateral plaques and carotid stenosis, non HDL cholesterol about the presence of carotid stenosis and stenosis of the internal carotid artery. These results can contribute in the refresment of the criteria for screening programes for CARD in the population with T2DM. PMID- 26355921 TI - [Organizational aspects of managing patients with atherosclerosis obliterans of lower-limb vessels at an ambulatory stage]. AB - The authors describe their first experience of a new approach in dispensary follow up of patients presenting with atherosclerosis obliterans of lower extremities vessels. The work was based on the municipal system of rendering outpatient medical care in the city of Kemerovo. The patients were subdivided into two groups: one group remained under supervision of the surgeon, the other one was referred to the cardiologist. The mean duration of follow up amounted to 12 +/- 1.5 months. The scope of carried out diagnostic, therapeutic and preventive procedures was assessed. The new approach to outpatient follow up, i. e., participation of the cardiologist in the therapeutic process made it possible to improve quality of medical care, also revealing positive alterations in diagnosis, treatment, and prevention of atherosclerosis obliterans of lower-limb vessels. PMID- 26355920 TI - [Pharmacological preconditioning in carotid endarterectomy]. AB - The study was aimed at examining efficacy of preoperative preparation (pharmacological preconditioning) for carotid endarterectomy in patients with chronic cerebrovascular insufficiency. For this purpose, we analysed the outcomes of surgical treatment in a total of 80 patients presenting with haemodynamically significant unilateral and bilateral lesions of carotid arteries. Of these, 40 patients were operated on immediately and a further 40 patients underwent surgery after pharmacological preconditioning with Actovegin taken at a daily dose of 1,200 mg for 1.5 months. It was demonstrated that preoperative preparation prior to surgery increases cerebral perfusion which is determined by means of single photon emission computed tomography, thus substantially improving the outcomes of surgical treatment. Statistically significant differences in cognitive function of these groups of patients were revealed 7 days and 6 months after the operation. Improvement of cognitive functions was associated with fewer symptom free postoperative cerebral ischaemic foci in various regions of the brain. A conclusion was made on a positive role of pharmacological preconditioning with Actovegin in surgical management of cerebrovascular insufficiency, first of all in relation to more complete restoration of cognitive functions. PMID- 26355922 TI - [Ways to improve diagnosis and surgical treatment for pathology of brachiocephalic arteries]. AB - Over 2010-2013 we anonymously interrogated a total of 397 therapeutists of municipal polyclinics of six regions of Russia (Chelyabinsk, Kurgan, Sverdlovsk, Orenburg, and Saratov Regions and the Republic of Bashkortostan), studying their awareness of the indications and AIM: of ultrasound examination of brachiocephalic arteries (US BCA) in patients presenting with arterial hypertension (AH) and revealing the physicians' attitude to carrying out surgical prevention of stroke in hypertensive patients. As the indications for USS BCA 35 (8.82%) of physicians reported symptoms of local cerebrovascular lesions, mentioning: "complaints of unilateral weakness in the extremities" (n=18), "complaints of speech impairments disorders" (n=2), "complaints of loss of fields of vision" (n=4), "endured TIA" (n=11). A total of 261 (65.74%) respondents considered the grounds for US BCA to be as non-specific cerebrovascular symptoms (isolated dizziness, headache, disequilibrium, syncope). 242 (60.96%) physicians with the purpose of examining asymptomatic hypertensive patients mentioned the type and character of a vascular lesion: 16 (4.03%) - "determining the intima media thickness"; (22 (5.4%) - "an atherosclerotic plaque"; 100 (25.18%) - "arterial stenoses/occlusions". 155 (39.04%) interrogated physicians failed to determine the AIM: of ultrasonic duplex scanning of major arteries of the head. 256 (64.65%) physicians answered that they do not recommend their hypertensive patients with AH to undergo surgical prevention of ischaemic stroke. The obtained findings reflect poor awareness of physicians of the primary medical care (PMC) on diagnostic criteria for cerebrovascular diseases (CVDs). The revealed problems concerning follow up of CVDs would help decide upon publication and active distribution of All-Russian guidelines for primary care physicians (therapeutists, cardiologists, neurologists, functionalinsts) on selection patients for BCA USS and angiosurgical interventions. A draft of the informational letter "Indications for BCA ultrasound examination" is attached to the article. PMID- 26355923 TI - [Endovascular treatment of traumatic arteriovenous fistulas of the vertebral artery]. AB - The authors describe herein the use of balloon-distensible stent grafts for endovascular treatment of patients presenting with traumatic arteriovenous fistulas in the first segment of the vertebral artery, exemplified by two clinical case reports. In both cases, the arteriovenous fistula formed after a stab-and-slash wound in the neck area. In order to exclude the arteriovenous aneurysm from the blood flow in the first case we performed endoprosthetic repair of the first segment of the subclavian artery with shutting off of the ostium of the vertebral artery carrying the aneurysm. In the second case, in order to remove the arteriovenous shunt we carried out performed endoprosthetic repair of the first segment of the vertebral artery. These cases show possibilities of roentgenoendovascular methods of treatment, making it possible to successfully replace technically complicated surgical interventions in traumatic arteriovenous fistulas of vertebral arteries. PMID- 26355924 TI - [Endovascular repair of an abdominal aortic aneurysm in a patient with horseshoe kidney]. AB - Presented herein is a case report concerning successful endovascular treatment of a patient with an infrarenal abdominal aortic aneurysm combined with a horseshoe kidney. The diagnosis was verified by multispiral computed tomography. The patient underwent of endovascular repair of the abdominal aorta with a stent graft AORFIX (Lombard Medical). The postoperative period turned out uneventful, with no complications. The patient was examined 3 years after the intervention. The findings of control check-up computed tomography showed no signs of either stent graft dislocation or endoleak. PMID- 26355925 TI - [Effect of pharmacotherapy on course of postoperative period after endovenous thermal ablation]. AB - The authors assessed the effect of a micronized purified flavonoid fraction (MPFF) on the course of the postoperative period after endovenous thermal ablation (EVTA). The patients of the Study Group matching by the main studied parameters to the Control Group patients were given the MPFF according to the suggested regimen for 7 days. The obtained results were analysed by means of questionnaires (CIVIQ, VCSS, VAS) and ultrasound angioscanning. The obtained findings were statistically processed by means of the program Statistica 6.0 and reliability of the results was assessed with the help of the Student t-test. Patients of the both groups showed complete stable obliteration of the target veins. No statistically significant differences of the items of the questionnaires CIVIQ and VCSS at the beginning of the study and at the last examination were revealed, differences were noted on days 2-14 after EVTA and were not statistically significant (p>0.05). Phlebotrophic therapy in the postoperative period after EVTA helps to decrease phlebitic alterations in the coagulated vein, to improve motor activity and mental psychoemotional state of the patients. PMID- 26355926 TI - [Endogenous venous thrombolysis]. AB - Widely incorporated into vascular surgery pharmacological thrombolysis in treatment for deep vain thrombosis is fraught with a series of unsolved problems requiring further consideration. In spite of aggressive nature of treatment in a series of cases pharmacological thrombolysis sometimes turns out ineffective. Along with it, the results of experimental studies suggest a possibility of accelerating resorption of thrombotic masses and inhibiting remodelling of the venous wall by means of influencing effector cells of endogenous thrombolysis. A detailed study of the mechanisms of thrombolysis would make it possible to formulate strict criteria for carrying out pharmacological thrombolysis and to increase its efficacy. PMID- 26355927 TI - [Possibilities of pharmacotherapy for chronic venous insufficiency with diosmin preparations from the position of the endothelial functional state]. AB - Despite a high level of the development of modern angiology and vascular surgery, the problem of chronic venous insufficiency (CVI) complicating the course of various venous diseases seems to have no tendency towards being solved, thus calling forth permanent search for optimization of methods of treatment and rehabilitation of patients presenting with the above-mentioned syndrome. The article presents a review of contemporary studies dedicated to the problem of correcting CVI. Special attention is paid to the endothelial state in CVI and possibilities of correcting endothelial dysfunction with the use of bioflavonoids, in particular, diosmin. Also presented herein are the results of an original experimental study dedicated to peculiarities of the endothelial functional state, endothelial dysfunction, and correction thereof on the background of the existing CVI. PMID- 26355928 TI - [Significance of endothelial protection in treatment of patients with class c6 chronic venous disease and type 2 diabetes mellitus]. AB - The authors studied efficacy of using sulodexide (Vessel Due F) in treatment of patients with clinical class C6 chronic venous disease (CVD) and type 2 diabetes mellitus (DM). The study included a total of sixty-two 18-to-75-year-old patients of both sexes suffering from class C6 CVD and type 2 DM. The patients were randomly assigned to either the Study Group (Group I) and Control Group (Group II) in the ratio of 1:1. The Study Group patients received treatment with sulodexide according to the standard regimen during 50 days. The study included taking case history, examination by a phlebologist and endocrinologist, measuring the malleolar volume, body weight, ultrasound examination of lower-limb vessels, clinical and biochemical blood analyses, coagulogram, planimetry of trophic ulcers, microbiological and cytological study. The primary end point was epithelialization of trophic ulcers after 1 month. Secondary endpoints were ulcer healing after 2 months and dynamic alterations during epithelialization. The Study Group patients as compared to the Control Group patients were found to have statistically significant improvement of the composite index of clinical assessment of VSCC severity, decrease in the malleolar volume, positive dynamics of speed velocity parameters of venous outflow and improvement of quality of life according to the SF-36 questionnaire. After 30 days, epithelialization was achieved in 11 (33.5%) cases in the Study Group and in 6 (19.4%) cases in the Control Group (p<0.05). After 60 days, epithelialization was achieved in 27 (87.1%) and 15 (48.4%) patients of the Study and Control Groups, respectively. The time to complete epithelialization in Group I and II patients amounted to 49.8 +/- 1.4 and 76.6 +/- 2.4 days, respectively (p<0.05). A conclusion was drawn that administration of sulodexide (Vessel Due F) is effective and pathogenetically substantiated in treatment of patients presenting with class C6 CVD and type 2 DM. PMID- 26355929 TI - [Carbonization in endovasal laser obliteration by radial light guide with wavelength of 1470 and 970 nm]. AB - The authors assessed the effect of carbonization and its influence on the parameters of endovasal laser obliteration (EVLO) depending on wavelength of laser radiation (970 and 1470 nm) using a light guide with radial emission. They also analysed the value of drop of radiation power of the light guide after performing EVLO and visually assessed the degree of damage of the glass tip of the radial fibre by means of ultra-close-up photography. The study comprised a total of 20 patients with varicose disease. A total of ten procedures of EVLO were performed in two modes: mode one - W-laser 1470 nm, mode two - H-laser 970 nm, using fibre with radial emission, an automatic retractor of the light guide. It was determined that the median of power loss after EVLO with W-laser amounted to 0.6 W, and that for H-laser - 3.15 W (p=0.002). Ultra-close-up photography showed pronounced damage of the glass tip of the radial light guide while using H laser and no damages while using the W-laser. It was proved that using laser radiation with wavelength of 970 nm using the light guide with radial emission leads to pronounced carbonization on the surface of the glass tip of the light guide, its damage, a decrease in radiation power and risk of mechanical destruction of the flask. Using the laser with wavelength of 1470 nm with the use of radial light guide did not result in the development of such negative effects, which increases the service life of laser fibre and makes it possible to use it for obliteration of several segments in one patient. PMID- 26355930 TI - [Peculiarities of diagnosis and surgical policy in elderly patients with pathological tortuosity of the internal carotid artery]. AB - The study was aimed at optimizing surgical treatment management of elderly patients presenting with pathological tortuosity of the internal carotid artery (ICA). We examined a total of 94 patients with unilateral haemodynamically significant tortuosity of the ICA. Depending on the age, the patients were subdivided into two groups: Group One comprising forty-six (49%) 50-to-60-year old patients and Group Two consisting of 48 (51%) patients above 60 years (from 61 to 84 years). 37% of patients had were found to have pathological tortuosity combined with haemodynamically significant ICA stenosis. In these patients linear blood velocity in the zone of the largest deformation was by 15% less than in patients with isolated tortuosity (p<0.05). All patients underwent reconstructive operations of carotid arteries with a good clinical effect. A combination of stenosis and pathological tortuosity of the ICA was treated by eversion carotid endarterectomy with lowering down and reimplantation of the artery into the previous ostium; microaneurysms present in the ICA wall were managed by resection of the artery's portion with autovenous prosthetic repair or bringing down the artery into the previous ostium. In 77% of patients above 60 years the operation was carried out under regional anaesthesia. According to the findings of duplex scanning, rectilinearity of the ICA after surgery was restored in 100% of cases, blood flow was of major type, with no turbulence registered. It was demonstrated that surgical management of elderly patients with pathological tortuosity is an effective method of prevention of ischaemic stroke. The complications rate in patients presenting with combined atherosclerotic lesions of the ICA and its pathological tortuosity, should adequate surgical policy be employed, falls within the framework of the accepted standards and does not depend on the type of ICA lesion. PMID- 26355931 TI - [Outcomes of reconstructive operations on carotid arteries in acute period of ischaemic stroke]. AB - Analysed herein are the results of surgical treatment of 55 patients who from June 2013 to August 2014 underwent a total of 56 reconstructive operations on carotid arteries during an acute period of ischaemic stroke. The operations were performed within the terms varying from 24 hours to 18 days after the onset of first symptoms of ischaemic stroke. The neurological status was assesses by the neurologist according to the NIH Stroke Severity Scale (USA) and the Modified Rankin Scale. Prior to operation neurological deficit in 18 patients corresponded to 4 points by the Rankin Scale. Carotid endarterectomy was performed in 55 patients, of these in 24 according to the eversion technique. In 10 patients eversion carotid endarterectomy was performed in combination with ICA resection. One patient was simultaneously subjected to eversion carotid endarterectomy and carotid-subclavian shunting bypass grafting. Carotid endarterectomy with autovenous-patch plasty was performed in 11 patients. Resection of the occluded internal carotid artery with plasty of the external carotid artery was carried out in 7 patients and resection of the internal carotid artery for pathological tortuosity was carried out in 2 patients. At discharge from hospital, regression of neurological symptomatology was noted in 46 (83%) patients. Nine (20%) patients showed complete restoration of neurological deficit, two (4%) patients were found to have increased manifestations of neurological deficit. In the postoperative period two patients died: one on postoperative day 24 from augmenting respiratory and cardiac failure, the other one on day 29 from augmenting renal insufficiency followed by cardiac failure. In both cases, autopsy revealed no signs of secondary impairment of cerebral circulation. Surgical interventions on carotid arteries performed at a multimodality vascular centre during the first 18 days after the development of ischaemic stroke in the majority of cases are accompanied and followed by regression of neurological deficit, being safe concerning the development of haemorrhagic transformation. PMID- 26355932 TI - [Combined treatment of complicated forms of angiodysplasias in conditions of a multimodality hospital]. AB - Presented herein is a case report dealing with successive combined treatment for arteriovenous malformation of the left part of the chest, macrofistular form complicated by necroses of the left thoracic portion with arrosive haemorrhage from the area of necrosis. The authors describe diagnosis of this disease, technical peculiarities of performing transcatheter endovascular occlusion and topical treatment of wounds, underlining difficulties of verifying the pathology concerned at the prehospital stage and prevention of complications. Particular emphasis in management of these patients is placed upon therapeutic decision making. Radical excision of tissue practically completely consisting of dilated thin-walled vessels may result in massive perfuse haemorrhage and is often impossible. Selective exclusion of feeding arteries by endovascular methods frequently leads to formation of necroses, does not differ in radical nature because of the presence of multiple arteriovenous fistulas and requires regular follow up of the patient due to a possibility of relapse. The final therapeutic decision should be made in the context of a particular patient, since there are no versatile approaches to management of the pathology concerned. PMID- 26355933 TI - [Experience with cryopreserved homografts used in aortofemoral position in infection of vascular prostheses]. AB - The authors share herein their experience in reconstructive interventions on the aortofemoral segment in infection of the implant in three 59-to-69-year-old male patients. Infection of the prosthesis was diagnosed by the clinical data, findings of MSCT angiography and duplex scanning of the infrarenal portion of the aorta and arteries of lower limbs. Pseudoaneurysms of distal anastomoses were revealed in two cases. All secondary reconstructions were performed with the use of a cryopreserved aortic bifurcation homograft in the in situ position with simultaneous removal of the infected implant. The results of inoculation from the removed implants yielded Staphylococcus aureus in two cases and Staphylococcus epidermidis in one case. One patient died 6 months later due to causes not related to the operative intervention, in the remaining two cases during one year no findings suggesting reinfection or steno-occlusive lesion of the aortofemoral segment have been revealed. PMID- 26355934 TI - [Modern approaches to surgical treatment of post-injection vascular complications in intravenous drug addicts]. AB - An ever-growing number of injection drug abusers causes great concern over specific post-injection complications involving major vessels, not uncommonly infected ones. The review is dedicated to the problem of vascular complications in drug abusers, clinical peculiarities of the nosology concerned, as well as a present-day view on diagnosis and policy of surgical treatment of infected false aneurysms in this cohort of patients. Surgical decision-making is based on a series of factors: baseline general condition of the patient, possibility of surgical care depending on the specific situation (scope and level of the infected area, phase of the course of the wound process, degree of ischaemia of the limb, choice of a plastic material), and probability of further injections of narcotic drugs. In treatment of such patients a promising trend includes endovascular and minimally invasive technologies, however assessing the remote results thereof requires accumulation of larger experience. PMID- 26355935 TI - [Use of a biological graft for subclavian-femoral bypassing in patients at operational-anaesthesiological risk]. AB - Analysed herein are the results of an experimental study performed on 30 rabbits and a clinical study of treating a total of 60 patients presenting with critical ischaemia of lower limbs on the background of bilateral atherosclerotic lesions of the aortoiliac segment and running high operational-anaesthesiological risk. The animals were subdivided into three groups: an intact group consisting of 6 animals and two study groups comprising 12 rabbits each. In the first study group onto the wall of the abdominal aorta we implanted a synthetic polytetrafluoroethylene prosthesis, the second study group animals received biological graft "Kemangioprotez" from bovine internal thoracic arteries. The biological prosthesis on day three after implantation onto the arterial wall induced 3.2 times and on day seven 1.2 times more pronounced inflammatory reaction than the polytetrafluoroethylene prosthesis. 30 days after implantation of the synthetic graft the degree of repair connective-tissue processes in the arterial wall was 1.8-fold and 70 days after was 3.3-fold more pronounced than after implantation of the biological prosthesis at the same terms. In the connective-tissue capsule around the synthetic prosthesis predominated cellular elements while around the biological prosthesis - fibrous structures predominated. The patients were subdivided into 2 groups consisting of 30 patients each. In Group One patients the shunt used was a synthetic polytetrafluoroethylene prosthesis, in Group Two being a biological graft from bovine internal thoracic arteries. All patients suffered from severe concomitant diseases in the decompensation stage and a multi-level lesion of lower-limb arteries. Revascularization of the ischaemized extremity was carried out through the system of the deep femoral artery system. The use of a biological prosthesis made it possible in the immediate postoperative period to decrease the frequency of early postoperative complications by 13.3%, that of late graft thromboses by 30%, to prolong the average term of grafts functioning 1.8-fold, to increase the physical component of health by 12.8% and the mental one by 9.1%. CONCLUSION: For femorosubclavian shunting in high-risk patients it is appropriate to use a biological graft while establishing a distal anastomosis with the deep femoral artery. PMID- 26355936 TI - [Surgical treatment of an aneurysm of the upper mesenteric artery]. AB - Presented herein is a clinical case report concerning successful surgical treatment of an aneurysm of the upper superior mesenteric artery. Diagnosis included contrast-enhanced multispiral computed tomography. Thought the middle laparotomy we exposed an aneurysm of the superior mesenteric artery measuring 3 mm in diameter. A peculiarity of the aneurysm was that it was tightly adhered to the body of the pancreas and had a "neck" with pronounced signs of infiltration, with the latter extending to the right lateral and upper wall of the aneurysm. The aneurysm was resected along its "neck" which made it possible to suture the defect without residual stenosis and with no use of a synthetic patch. The woman was discharged on day 8 postoperatively in a satisfactory condition. Based on the morphological examination of the micropreparation the following diagnosis was made: fibromuscular dysplasia, aneurysm of the superior mesenteric artery. PMID- 26355937 TI - Use of polymethylmethacrylate in treatment of arteriovenous angiodysplasia with bone lesions. AB - Arteriovenous dysplasia is rather uncommon disease, quite often leading to severe complications even in young age. Involvement of the osseous apparatus into the pathological process is frequently associated with the problem of amputation of the affected limb. Therefore, salvage of the extremity while removing arteriovenous shunt and trophic impairments is an extremely important clinical task. In the presented herein clinical case report, a female patient with arteriovenous angiodysplasia of the lower limb with the tibial bone involved into the pathological process underwent repeated stagewise embolisations, failing however to achieve complete liquidation of the arteriovenous reflux. In this connection, after removal of angiomatous tissues, requiring also excochleation of the damaged portions of the bone, in order to reinforce the axis of the tibial bone the intramedullary canal of the latter was filled with polymethylmethacrylate (PMMA). Expansion of the spectrum of auxiliary methods, besides the most frequently performed in such patients embolisations of afferent arteries and removal of angiomatous tissues would make it possible to increase radical nature of interventions with salvage of the supporting function of limbs. PMID- 26355938 TI - [Liver resection in patient with hcc and right atrium thrombosis]. AB - Presented herein is a case report concerning tumorous thrombosis of the inferior vena cava and right atrium, which is rather an uncommon but severe complication of primary hepatic cancer. The purpose of the article is to demonstrate successful surgical management of locally disseminated hepatic carcinoma complicated by tumorous thrombosis of the inferior vena cava and portal vein, as well as thrombosis of the right atrium. The patient was subjected to dextral hemihepatectomy with thrombectomy from the right portal vein, resection of the right cupola of the diaphragm, marginal resection of the lower lobe of the right lung, thrombectomy from the inferior vena cava and right atrium. The outcome of our case report, as well as literature data suggest that in case of resectability of hepatic tumour complicated by thrombosis of major vessels and even the heart, surgical intervention is justified if there is a possibility to completely remove thrombotic masses along with the primary tumour. PMID- 26355939 TI - [Endovascular treatment of spontaneous rupture of the thoracic aorta]. AB - Spontaneous rupture of the aorta is an uncommonly encountered acute surgical aortic pathology characterised by an utterly unfavourable prognosis. The article deals with a case report concerning successful endovascular treatment of spontaneous rupture of the thoracic portion of the aorta, followed by discussion of problems regarding aetiology, diagnosis, and therapeutic policy for such pathology. PMID- 26355940 TI - Neotropical echinococcosis caused by Echinococcus vogeli in a 6-year-old child: the second case report in humans in French Guiana. AB - Human polycystic echinococcosis is a parasitic infection caused by the larval stage of Echinococcus vogeli which occurs in rural areas of Central and South America. Abdominal echinococcosis caused by E. vogeli is reported for the first time in a child, a 6-year-old boy in French Guiana. The diagnosis was made by histological and molecular techniques. In tropical regions, this neglected disease must be considered even in children. PMID- 26355941 TI - Polymorphism of amyloid-like fibrils can be defined by the concentration of seeds. AB - Prions are infectious proteins where the same protein may express distinct strains. The strains are enciphered by different misfolded conformations. Strain like phenomena have also been reported in a number of other amyloid-forming proteins. One of the features of amyloid strains is the ability to self propagate, maintaining a constant set of physical properties despite being propagated under conditions different from those that allowed initial formation of the strain. Here we report a cross-seeding experiment using strains formed under different conditions. Using high concentrations of seeds results in rapid elongation and new fibrils preserve the properties of the seeding fibrils. At low seed concentrations, secondary nucleation plays the major role and new fibrils gain properties predicted by the environment rather than the structure of the seeds. Our findings could explain conformational switching between amyloid strains observed in a wide variety of in vivo and in vitro experiments. PMID- 26355942 TI - Multicenter observational study comparing sedation/analgesia protocols for laser photocoagulation treatment of retinopathy of prematurity. AB - OBJECTIVE: The aim of this study was to identify the best sedation/analgesia protocol for laser photocoagulation (PC) of retinopathy of prematurity (ROP). STUDY DESIGN: This multicenter observational study included five hospitals, each using a specific sedation/analgesia protocol: local anesthesia with oxybuprocaine hydrochloride (Group L); intravenous pentazocine (Group P); intravenous fentanyl (Group F); air, oxygen and sevoflurane (AOS) inhalation (Group I). The groups were compared for pain responses, vital signs and adverse events. RESULTS: Heart rates and systemic blood pressures were elevated by PC in Groups L and P and Groups L, P and F, respectively. Moreover, poor analgesic efficacy was recognized in Groups L, P and F. In contrast, Group I experienced hypothermia, enteral feeding intolerance and apnea more frequently. CONCLUSION: From the viewpoint of sedation/pain relief, AOS anesthesia should be the best protocol. However, considering all the various factors together, the most reasonable one can be varied based on the patient's condition and hospital. PMID- 26355944 TI - 454 Pyrosequencing-based assessment of bacterial diversity and community structure in termite guts, mounds and surrounding soils. AB - Termites constitute part of diverse and economically important termite fauna in Africa, but information on gut microbiota and their associated soil microbiome is still inadequate. In this study, we assessed and compared the bacterial diversity and community structure between termites' gut, their mounds and surrounding soil using the 454 pyrosequencing-based analysis of 16S rRNA gene sequences. A wood feeder termite (Microcerotermes sp.), three fungus-cultivating termites (Macrotermes michaelseni, Odontotermes sp. and Microtermes sp.), their associated mounds and corresponding savannah soil samples were analyzed. The pH of the gut homogenates and soil physico-chemical properties were determined. The results indicated significant difference in bacterial community composition and structure between the gut and corresponding soil samples. Soil samples (Chao1 index ranged from 1359 to 2619) had higher species richness than gut samples (Chao1 index ranged from 461 to 1527). The bacterial composition and community structure in the gut of Macrotermes michaelseni and Odontotermes sp. were almost identical but different from that of Microtermes and Microcerotermes species, which had unique community structures. The most predominant bacterial phyla in the gut were Bacteroidetes (40-58 %), Spirochaetes (10-70 %), Firmicutes (17-27 %) and Fibrobacteres (13 %) while in the soil samples were Acidobacteria (28-45 %), Actinobacteria (20-40 %) and Proteobacteria (18-24 %). Some termite gut-specific bacterial lineages belonging to the genera Dysgonomonas, Parabacteroides, Paludibacter, Tannerella, Alistipes, BCf9-17 termite group and Termite Treponema cluster were observed. The results not only demonstrated a high level of bacterial diversity in the gut and surrounding soil environments, but also presence of distinct bacterial communities that are yet to be cultivated. Therefore, combined efforts using both culture and culture-independent methods are suggested to comprehensively characterize the bacterial species and their specific roles in these environments. PMID- 26355943 TI - Stem Cell Strategies to Evaluate Idiosyncratic Drug-induced Liver Injury. AB - The host-dependent nature of idiosyncratic drug-induced liver injury (iDILI) suggests that rare genetic polymorphisms may contribute to the disease. Indeed, a few mutations in key genes have already been identified using conventional human genetics approaches. Over 50 commonly used drugs can precipitate iDILI, making this a substantial medical problem. Only recently have human induced pluripotent stem cells been used as a research tool to discover novel iDILI genes and to study the mechanisms of iDILI in vitro. Here we review the current state of stem cell use in the investigation of iDILI, with a special focus on genetics. In addition, the concerns and difficulties associated with genetics and animal model research are discussed. We then present the features of patient-specific pluripotent stem cells (which may be derived from iDILI patients themselves), and explain why these cells may be of great utility. A variety of recent approaches to produce hepatocyte-like cells from pluripotent cells and the associated advantages and limitations of such cells are discussed. Future directions for the use of stem cell science to investigate iDILI include novel ways to identify new iDILI genes, a consideration of epigenetic impacts on iDILI, and the development of new and improved strategies for the production of hepatocytes from human pluripotent cells. PMID- 26355945 TI - Isoniazid-induced polyneuropathy in a tuberculosis patient - implication for individual risk stratification with genotyping? AB - BACKGROUND: Development of polyneuropathy (PNP) under treatment for tuberculosis (TB), including isoniazid (INH), is a highly relevant adverse drug effect. The NAT2 acetylation status is a predictor of potential toxic effects of INH. The question as to whether individual risk stratification by genotyping is useful to avoid suffering of patients and to lower costs for the health care system is of considerable clinical importance. CASE PRESENTATION: After drug treatment for TB, including INH, a 23-year-old man developed severe PNP. During the treatment, laboratory results have been indicating incipient liver and renal injury. Later, molecular genetic analyses were performed and revealed a variation in the NAT2 gene and the c1/c2 genotype of the CYP2E1 gene, both described to contribute to an elevated risk for anti-tuberculostatic-induced liver damages (ATIL). CONCLUSION: The combination of metabolizer genotypes should be taken into account as a cause for toxic effects and the development of PNP. Individual genotyping, performed before medication or at least if an elevation of liver parameters is observed, may reduce the risk of severe cases of PNP by early adjustment of treatment. Our case study indicates that evaluation of individual risk stratification with systematic pharmacogenetic genotyping of metabolizer gene combinations in the context of TB treatment should be addressed in clinical studies with larger cohorts. PMID- 26355946 TI - TRANSCLERAL DRAINAGE OF SUBRETINAL FLUID, ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR, AND WIDE-FIELD IMAGING-GUIDED LASER IN COATS EXUDATIVE RETINAL DETACHMENT. AB - PURPOSE: To evaluate the safety and efficacy of combined transscleral drainage of subretinal fluid (SRF) with intravitreal bevacizumab and laser photocoagulation in the management of advanced Coats disease (Stage 3) with exudative retinal detachment. DESIGN: Retrospective interventional case series. METHODS: Retrospective case review of eight eyes in eight children with advanced Coats disease manifested as total or subtotal retinal detachment. All eyes initially underwent surgical drainage of exudative SRF followed by intravitreal injection of bevacizumab and laser photocoagulation. Patients were subsequently followed up for up to 60 months. RESULTS: In all eyes, after SRF drainage and administration of one to two intravitreal injections, SRF was completely eliminated. Patients required up to four sessions of laser photocoagulation. Retinal detachment consequently reduced with all patients showing total retinal reattachment and resolution of the subretinal exudates. At the last follow-up, no patient showed recurrent SRF and no ocular complications related to bevacizumab nor evidence of further disease progression were noted. CONCLUSION: The authors present a new therapeutic approach that allows for the first time successful treatment of advanced cases of exudative retinal detachment in Coats disease without the need for vitrectomy. Transscleral drainage of SRF accompanied by anti-vascular endothelial growth factor injection and laser photocoagulation appears to be successful in halting progression of advanced Coats disease with exudative detachment and a less invasive approach when compared with conventional management. PMID- 26355947 TI - INTRAVITREAL RANIBIZUMAB FOR CHOROIDAL NEOVASCULARIZATION IN ANGIOID STREAKS: Four-Year Follow-up. AB - PURPOSE: To analyze retrospectively the efficacy of intravitreal ranibizumab injections for the management of choroidal neovascularization in patients with angioid streaks over a long term. METHODS: In this "nonrandomized," double center, retrospective, interventional case series, a consecutive series of patients affected with choroidal neovascularization associated with angioid streaks were treated with intravitreal ranibizumab injections (0.5 mg/0.05 mL). Best-corrected visual acuity, fundus photography, optical coherence tomography, and fluorescein angiography were examined before and after treatment. The primary endpoint was the percentage of eyes with stable or improved visual acuity at the end of follow-up (loss of less than 3 Early Treatment Diabetic Retinopathy Study lines). Secondary endpoints were the percentage of eyes with stable or decreased macular thickness on optical coherence tomography (less than a 10% increase in macular thickness) and the percentage of eyes with persistent leakage on fluorescein angiography at the last observation carried forward. RESULTS: Thirty five eyes of 27 patients were treated with repeated intravitreal ranibizumab injections (mean of 9.9 +/- 7.2 injections, range 2-26) for a mean of 48.6 +/- 17.1 months (range 8-66). At the end of follow-up, best-corrected visual acuity was stabilized or improved in 22 of 35 eyes (62.9%). Macular thickness had stabilized or decreased in 16 of 35 eyes (45.7%). At the last follow-up examination, on fluorescein angiography, no further leakage was observed in 27 of 35 eyes (77.1%). CONCLUSION: In this large series of patients with choroidal neovascularization associated with angioid streaks followed for 4 years, ranibizumab injections allowed stabilization of best-corrected visual acuity in most eyes. Ranibizumab appear as an effective therapeutic option in CNV associated with angioid streaks over long time. PMID- 26355948 TI - BRIDGE ARCH-SHAPED SEROUS RETINAL DETACHMENT IN AGE-RELATED MACULAR DEGENERATION. AB - PURPOSE: To describe bridge arch-shaped serous retinal detachment (SRD) in exudative age-related macular degeneration and evaluate its functional outcomes. METHODS: In this monocentric, retrospective, noncomparative case series, patients were included. Patients with exudative age-related macular degeneration and bridge arch-shaped SRD treated with ranibizumab were included. Anatomical patterns of SRD and functional outcomes were assessed. RESULTS: Twenty-two eyes with bridge arch-shaped SRD of 22 patients with age-related macular degeneration were included. Serous retinal detachments were characterized by a steep angle at the junction between the retinal pigment epithelium and the sensory retina (mean, 53.45 +/- 12.5 degrees ), and characterized by the presence of adhesion areas between the sensory retina and a fibrous complex developed from the choroidal neovascularization. In 15 eyes, the choroidal neovascularization was classic choroidal neovascularization and a fibrotic evolution was observed. Serous retinal detachments were compartmentalized in 14 eyes, leading to a multipocket structure. Visual acuity decreased from 49.9 +/- 19.2 letters (20/100) to 40.3 +/ 18.6 letters (20/160), corresponding to a mean change of -9.6 +/- 19.4 letters. CONCLUSION: This was the first study to describe the specific morphologic features of bridge arch-shaped SRD, a previously undescribed type of SRD complicating exudative age-related macular degeneration. Patients with bridge arch-shaped SRD responded to intravitreal injections of ranibizumab, but their visual prognosis was unfavorable, compared with the literature. The presence of bridge arch-shaped SRD seemed to be a marker for the fibrotic evolution of the choroidal neovascularization. PMID- 26355949 TI - Endogenous Two-Photon Excited Fluorescence Provides Label-Free Visualization of the Inflammatory Response in the Rodent Spinal Cord. AB - Activation of CNS resident microglia and invasion of external macrophages plays a central role in spinal cord injuries and diseases. Multiphoton microscopy based on intrinsic tissue properties offers the possibility of label-free imaging and has the potential to be applied in vivo. In this work, we analyzed cellular structures displaying endogenous two-photon excited fluorescence (TPEF) in the pathologic spinal cord. It was compared qualitatively and quantitatively to Iba1 and CD68 immunohistochemical staining in two models: rat spinal cord injury and mouse encephalomyelitis. The extent of tissue damage was retrieved by coherent anti-Stokes Raman scattering (CARS) and second harmonic generation imaging. The pattern of CD68-positive cells representing postinjury activated microglia/macrophages was colocalized to the TPEF signal. Iba1-positive microglia were found in areas lacking any TPEF signal. In peripheral areas of inflammation, we found similar numbers of CD68-positive microglia/macrophages and TPEF-positive structures while the number of Iba1-positive cells was significantly higher. Therefore, we conclude that multiphoton imaging of unstained spinal cord tissue enables retrieving the extent of microglia activation by acquisition of endogenous TPEF. Future application of this technique in vivo will enable monitoring inflammatory responses of the nervous system allowing new insights into degenerative and regenerative processes. PMID- 26355950 TI - Hypogonadotropic Hypogonadism in Infants with Congenital Hypopituitarism: A Challenge to Diagnose at an Early Stage. AB - BACKGROUND: Combined pituitary hormone deficiency (CPHD) presents a wide spectrum of pituitary gland disorders. The postnatal gonadotropic surge provides a useful period to explore the gonadotropic axis for assessing the presence of congenital hypogonadotropic hypogonadism (CHH). AIM: To explore the functioning of the hypothalamic-pituitary-gonadal axis in the postnatal gonadotropic surge for an early diagnosis of CHH in newborns or infants suspected of having CPHD. SUBJECTS AND METHODS: A cohort of 27 boys under 6 months and 19 girls under 24 months of age with suspected hypopituitarism was studied. Serum concentrations of LH, FSH, testosterone, inhibin B, anti-Mullerian hormone (AMH) and estradiol were measured, and male external genitalia were characterized as normal or abnormal (micropenis, microorchidism and/or cryptorchidism). RESULTS: CPHD was confirmed in 36 out of 46 patients. Low LH and testosterone levels were found in 66% of the hypopituitary males, in significant association with the presence of abnormal external genitalia. This abnormality had a positive predictive value of 93% for CHH. No significant association was observed between serum FSH, AMH and inhibin B and the patient's external genitalia. CONCLUSION: In newborn or infant boys with CPHD, LH and testosterone concentrations measured throughout the postnatal gonadotropic surge, together with a detailed evaluation of the external genital phenotype, facilitate the diagnosis of CHH at an early stage. PMID- 26355951 TI - Epidermal Hydration Is Improved by Enhanced Ceramide Metabolism in Aged C57BL/6J Mice After Dietary Supplementation of Royal Jelly. AB - Epidermal hydration is maintained by the epidermal lipid barrier, of which ceramide (Cer) is the major constituent. We examined the dietary effect of royal jelly (RJ) on epidermal hydration in aged mice. Altered Cer metabolism was further determined by measuring epidermal levels of individual Cer, glucosylceramide (GC), and sphingomyelin (SM) species, and of Cer-metabolizing enzymes. Aged C57BL/6J mice were fed a control diet (group AGED) or diets with 1% RJ harvested from two different areas (groups AGED+RJ1:AGED + RJ2) for 16 weeks. Aged C57BL/6J mice with no dietary intervention (the control group: group C) represented the onset of aging. In group AGED, epidermal levels of hydration, Cer1/2/5/6/7, GC-A/B/C/D, SM1/2/3, and beta-glucocerebrosidase (GCase) protein, an enzyme of GC hydrolysis for Cer generation, were lower than in group C; these levels, as well as those of Cer3/4 and acidic sphingomyelinase (aSMase) protein, an enzyme of SM hydrolysis for Cer generation, were higher in group AGED + RJ1 than in group AGED. Despite increases in GC-B, SM1/2/3, and serine palmitoyltransferase2 protein, an enzyme of de novo Cer synthesis, in group AGED + RJ2 to levels higher than in group AGED, epidermal levels of hydration, Cer1-7, GC-A/C/D, GCase, and aSMase proteins were similar in these two groups. Expression of GCase and aSMase mRNAs, and of Cer synthase3 and ceramidase proteins, enzymes of de novo Cer synthesis and degradation, did not differ among groups. Dietary RJ1 improved epidermal hydration by enhancing Cer metabolism with increased levels of all Cer, GC, and SM species, and of GCase and aSMase proteins. PMID- 26355952 TI - Support of Joint Function, Range of Motion, and Physical Activity Levels by Consumption of a Water-Soluble Egg Membrane Hydrolyzate. AB - This study evaluated the effects of consumption of hydrolyzed water-soluble egg membrane (WSEM) on joint function in an otherwise healthy population experiencing chronic pain. A randomized, double-blind, placebo-controlled crossover study included two 4-week periods of placebo and WSEM consumption, separated by a 4 week washout period. Twenty-five study participants were randomized to either the "placebo-first" or "WSEM first" sequence in the crossover trial, and 22 participants completed the study requirements. Range of motion (ROM) was assessed using digital inclinometry for joints associated with vertical weight bearing from neck to knees and for shoulders. Pain at rest and when physically active was scored for the same anatomical areas using visual analog scales (VAS). Physical functioning was tracked using questionnaires with VAS. Consumption of WSEM was associated with improved ROM for neck, spine, hips, and knees, with ROM for the neck and right knee being significantly improved during WSEM consumption compared to placebo (P < .05). ROM improvement for the dominant shoulder was highly significant during WSEM consumption (P < .01). Physical activity levels were significantly higher after WSEM than after placebo consumption (P < .05). Many aspects of physical functioning as part of daily living improved. Subgroup analysis showed rapid improvement of lower back pain after 5 days of WSEM consumption compared to placebo consumption (P < .05) in subjects who participated in the study during the winter season. Daily consumption of 450 mg WSEM was associated with improved joint function, comfort during daily activities, and increased physical activity. PMID- 26355953 TI - Toxicity Assessment of Common Beans (Phaseolus vulgaris L.) Widely Consumed by Tunisian Population. AB - This research aimed at assessing the content and the functional properties of phytohemagglutinin (PHA) in different varieties of beans widely consumed in Tunisia through soaking, cooking, autoclaving, germination, and their combinations. This study was carried out on three varieties of white beans grown in different localities of Tunisia, namely Twila, Coco, and Beldia, as well as on imported and local canned beans. All bean samples underwent biochemical and immunological evaluation by employing several techniques such as indirect competitive enzyme-linked immunosorbent assay (ELISA), hemagglutinating assay, Ouchterlony double immunodiffusion, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Biochemical and immunological analyses indicated that raw dry beans contained a considerable amount of proteins and PHAs. ELISA demonstrated that soaking, either in plain water or in alkaline solution, caused an increase in the concentration of PHA. A slight increase of PHA was produced equally by germination during 4 days in all bean varieties. Cooking or autoclaving of presoaked beans resulted in a complete disappearance of PHA. ELISA test also proved that both imported and local canned beans contained fingerprints of PHA. Hemagglutination assays showed that not only cooked and autoclaved presoaked beans lacked the ability to agglutinate red blood cells but also autoclaved unsoaked beans did. In agar gel immunodiffusion using rabbit anti-PHA serum, raw, soaked, cooked unsoaked, and sprouted beans gave precipitin arc reactions, indicating that PHA existed in immunoreactive form in the tested seeds. SDS-PAGE electrophoretograms showed protein isolates of Twila and Beldia beans to have different profiles through soaking, cooking, and autoclaving processes. This work revealed that the combination of soaking and cooking/autoclaving was the best way in reducing PHA content and its activity in all bean varieties when compared with germination. PMID- 26355954 TI - Pomegranate (Punicagranatum) juice decreases lipid peroxidation, but has no effect on plasma advanced glycated end-products in adults with type 2 diabetes: a randomized double-blind clinical trial. AB - INTRODUCTION: Diabetes mellitus characterized by hyperglycemia could increase oxidative stress and formation of advanced glycated end-products (AGEs), which contribute to diabetic complications. The purpose of this study was to assess the effect of pomegranate juice (PJ) containing natural antioxidant on lipid peroxidation and plasma AGEs in patients with type 2 diabetes (T2D). MATERIALS AND METHODS: In a randomized, double-blind, placebo-controlled trial, 44 patients (age range 56+/-6.8 years), T2D were randomly assigned to one of two groups: group A (PJ, n=22) and group B (Placebo, n=22). At the baseline and the end of 12 week intervention, biochemical markers including fasting plasma glucose, insulin, oxidative stress, and AGE markers including carboxy methyl lysine (CML) and pentosidine were assayed. RESULTS: At baseline, there were no significant differences in plasma total antioxidant capacity (TAC) levels between the two groups, but malondialdehyde (MDA) decreased levels were significantly different (P<0.001). After 12 weeks of intervention, TAC increased (P<0.05) and MDA decreased (P<0.01) in the PJ group when compared with the placebo group. However, no significant differences were observed in plasma concentration of CML and pentosidine between the two groups. CONCLUSIONS: The study showed that PJ decreases lipid peroxidation. Therefore, PJ consumption may delay onset of T2D complications related to oxidative stress. PMID- 26355955 TI - Structural Evolution of Nanoscale Zero-Valent Iron (nZVI) in Anoxic Co(2+) Solution: Interactional Performance and Mechanism. AB - The structures of nanoscale zero-valent iron (nZVI) particles evolving during reactions, and the reactions are influenced by the evolved structures. To understand the removal process in detail, it is important to investigate the relationships between the reactions and structural evolution. Using high resolution-transmission electron microscopy (HR-TEM), typical evolved structures (sheet coprecipitation and cavity corrosion) of nZVI in anoxic Co(2+) solutions were revealed. The system pH (pH measured in mixture), which controls the stability of coprecipitation and the nZVI corrosion rate, were found to be the determining factors of structural evolutions. X-ray photoelectron spectroscopy (XPS) results indicated that the formation and dissolution of sheet structure impacts on the ratio of Fe(0) on the nZVI surface and the surface Co(2+) reduction. The cavity structure provides the possibility of Co migration from the surface to the bulk of nZVI, leading to continuous removal. Subacidity conditions could accelerate the evolution and improve the removal; the results of structurally controlled reactions further indicated that the removal was suspended by the sheet structure and enhanced by cavity structure. The results and discussion in this paper revealed the "structural influence" crucial for the full and dynamical understanding of nZVI reactions. PMID- 26355956 TI - Uranium(III) redox chemistry assisted by a hemilabile bis(phenolate) cyclam ligand: uranium-nitrogen multiple bond formation comprising a trans {RN?U(VI)?NR}(2+) complex. AB - A new monoiodide U(III) complex anchored on a hexadentate dianionic 1,4,8,11 tetraazacyclotetradecane-based bis(phenolate) ligand, [U(kappa(6) {((tBu2)ArO)2Me2-cyclam})I] (1), was synthesized from the reaction of [UI3(THF)4] (THF = tetrahydrofuran) and the respective potassium salt K2((tBu2)ArO)2Me2 cyclam and structurally characterized. Reactivity of 1 toward one-, two-, and four-electron oxidants was studied to explore the reductive chemistry of this new U(III) complex. Complex 1 reacts with one-electron oxidizers, such as iodine and TlBPh4, to form the seven-coordinate cationic uranium(IV) complexes [U(kappa(6) {((tBu2)ArO)2Me2-cyclam})I][X] (X = I (2-I), BPh4 (2-BPh4)). The new uranium(III) complex reacts with inorganic azides to yield the pseudohalide uranium(IV) complex [U(kappa(6)-{((tBu2)ArO)2Me2-cyclam})(N3)2] (4) and the nitride-bridged diuranium(IV/IV) complex [(kappa(4)-{((tBu2)ArO)2Me2-cyclam})(N3)U(MU N)U(kappa(5)-{((tBu2)ArO)2Me2-cyclam})] (5). Two equivalents of [U(kappa(6) {((tBu2)ArO)2Me2-cyclam})I] (1) effect the four-electron reduction of 1 equiv of PhN?NPh to form the bis(imido) complex [U(kappa(4)-{((tBu2)ArO)2Me2 cyclam})(NPh)2] (6) and the U(IV) species 2-I. Moreover, the hemilability of the hexadentate ancillary ligand ((tBu2)ArO)2Me2-cyclam(2-) allows to perform the reductive cleavage of azobenzene with an unprecedented formation of a trans bis(imido) complex. The complexes were characterized by NMR spectroscopy, and all the new uranium complexes were structurally authenticated by single-crystal X-ray diffraction. PMID- 26355957 TI - Correction: Patterns of Protein Evolution in Cytochrome c Oxidase 1 (COI) from the Class Arachnida. AB - [This corrects the article DOI: 10.1371/journal.pone.0135053.]. PMID- 26355960 TI - Shaping and patterning gold nanoparticles via micelle templated photochemistry. AB - Shaping and positioning noble metal nanostructures are essential processes that still require laborious and sophisticated techniques to fabricate functional plasmonic interfaces. The present study reports a simple photochemical approach compatible with micellar nanolithography and photolithography that enables the growth, arrangement and shaping of gold nanoparticles with tuneable plasmonic resonances on glass substrates. Ultraviolet illumination of surfaces coated with gold-loaded micelles leads to the formation of gold nanoparticles with micro/nanometric spatial resolution without requiring any photosensitizers or photoresists. Depending on the extra-micellar chemical environment and the illumination wavelength, block copolymer micelles act as reactive and light responsive templates, which enable to grow gold deformed nanoparticles (potatoids) and nanorings. Optical characterization reveals that arrays of individual potatoids and rings feature a localized plasmon resonance around 600 and 800 nm, respectively, enhanced photothermal properties and high temperature sustainability, making them ideal platforms for future developments in nanochemistry and biomolecular manipulation controlled by near-infrared-induced heat. PMID- 26355959 TI - WDR5 Expression Is Prognostic of Breast Cancer Outcome. AB - WDR5 is a core component of the human mixed lineage leukemia-2 complex, which plays central roles in ER positive tumour cells and is a major driver of androgen dependent prostate cancer cell proliferation. Given the similarities between breast and prostate cancers, we explore the potential prognostic value of WDR5 gene expression on breast cancer survival. Our findings reveal that WDR5 over expression is associated with poor breast cancer clinical outcome in three gene expression data sets and BreastMark. The eQTL analysis reveals 130 trans-eQTL SNPs whose genes mapped with statistical significance are significantly associated with patient survival. These genes together with WDR5 are enriched with "cellular development, gene expression, cell cycle" signallings. Knocking down WDR5 in MCF7 dramatically decreases cell viability, but does not alter tumour cell response to doxorubicin. Our study reveals the prognostic value of WDR5 expression in breast cancer which is under long-range regulation of genes involved in cell cycle, and anthracycline could be coupled with treatments targeting WDR5 once such a regimen is available. PMID- 26355958 TI - Neutrophil Responses to Sterile Implant Materials. AB - In vivo implantation of sterile materials and devices results in a foreign body immune response leading to fibrosis of implanted material. Neutrophils, one of the first immune cells to be recruited to implantation sites, have been suggested to contribute to the establishment of the inflammatory microenvironment that initiates the fibrotic response. However, the precise numbers and roles of neutrophils in response to implanted devices remains unclear. Using a mouse model of peritoneal microcapsule implantation, we show 30-500 fold increased neutrophil presence in the peritoneal exudates in response to implants. We demonstrate that these neutrophils secrete increased amounts of a variety of inflammatory cytokines and chemokines. Further, we observe that they participate in the foreign body response through the formation of neutrophil extracellular traps (NETs) on implant surfaces. Our results provide new insight into neutrophil function during a foreign body response to peritoneal implants which has implications for the development of biologically compatible medical devices. PMID- 26355961 TI - A Robust and Versatile Method of Combinatorial Chemical Synthesis of Gene Libraries via Hierarchical Assembly of Partially Randomized Modules. AB - A major challenge in gene library generation is to guarantee a large functional size and diversity that significantly increases the chances of selecting different functional protein variants. The use of trinucleotides mixtures for controlled randomization results in superior library diversity and offers the ability to specify the type and distribution of the amino acids at each position. Here we describe the generation of a high diversity gene library using tHisF of the hyperthermophile Thermotoga maritima as a scaffold. Combining various rational criteria with contingency, we targeted 26 selected codons of the thisF gene sequence for randomization at a controlled level. We have developed a novel method of creating full-length gene libraries by combinatorial assembly of smaller sub-libraries. Full-length libraries of high diversity can easily be assembled on demand from smaller and much less diverse sub-libraries, which circumvent the notoriously troublesome long-term archivation and repeated proliferation of high diversity ensembles of phages or plasmids. We developed a generally applicable software tool for sequence analysis of mutated gene sequences that provides efficient assistance for analysis of library diversity. Finally, practical utility of the library was demonstrated in principle by assessment of the conformational stability of library members and isolating protein variants with HisF activity from it. Our approach integrates a number of features of nucleic acids synthetic chemistry, biochemistry and molecular genetics to a coherent, flexible and robust method of combinatorial gene synthesis. PMID- 26355962 TI - AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY POSITION STATEMENT ON THE ASSOCIATION OF TESTOSTERONE AND CARDIOVASCULAR RISK. AB - This document represents the official position of the American Association of Clinical Endocrinologists and the American College of Endocrinology. Where there were no randomized controlled trials or specific U.S. FDA labeling for issues in clinical practice, the participating clinical experts utilized their judgment and experience. Every effort was made to achieve consensus among the committee members. Position statements are meant to provide guidance, but they are not to be considered prescriptive for any individual patient and cannot replace the judgment of a clinician. PMID- 26355963 TI - LOW-DOSE ACTH STIMULATION TEST: DOSE, SAMPLING TIME, AND TECHNICAL ISSUES. PMID- 26355964 TI - Follicular Dendritic Cell Sarcoma: Cytogenetics and pathological findings. AB - Follicular dendritic cell sarcoma (FDCS) is a rare neoplasm with a non-specific and insidious presentation further complicated by the difficult diagnostic and therapeutic assessment. It has a low to intermediate risk of recurrence and metastasis. Unlike other soft tissue sarcomas or histiocytic and dendritic cell neoplasms, cytogenetic studies are very limited in FDCS cases. Although no specific chromosomal marker has yet been established, complex aberrations and different ploidy types have been documented. We report the case of a 39-year-old woman with FDCS who presented to the Sultan Qaboos University Hospital in Muscat, Oman, in February 2013. Ultrastructural, immunophenotypical and histological findings are reported. In addition, karyotypic findings showed deletions of the chromosomes 1p, 3q, 6q, 7q, 8q and 11q. To the best of the authors' knowledge, these have not been reported previously in this tumour. Techniques such as spectral karyotyping may help to better characterise chromosomal abnormalities in this type of tumour. PMID- 26355965 TI - Synthesis of Enantiomerically Pure Stereomers of Rosaprostol. AB - Enantiopure stereomers of rosaprostol 1, an antiulcer drug, were synthesized from diastereomeric building blocks (-)-5a and (+)-5b. Conversion of (-)-5a into rosaprostol stereomer (-)-(1S,2R,5R)-1a was accomplished in nine steps in 18% overall yield. In this sequence, fully diastereoselective hydrogeneration of the endocyclic carbon double bond in the cyclopentenone ring was key, generating a new stereogenic center (C-2 in 1a). C-5 epimeric rosaprostol (-)-(1S,2R,5S)-1b was obtained from (-)-1a in 72% yield by a two-reaction sequence involving methylation and one-pot Mitsunobu esterification-hydrolysis. PMID- 26355967 TI - The Urgent Need for the Development of Guidelines of Care for Patients With Craniofacial Deformities. PMID- 26355966 TI - Pili-Induced Clustering of N. gonorrhoeae Bacteria. AB - Type IV pili (Tfp) are prokaryotic retractable appendages known to mediate surface attachment, motility, and subsequent clustering of cells. Tfp are the main means of motility for Neisseria gonorrhoeae, the causative agent of gonorrhea. Tfp are also involved in formation of the microcolonies, which play a crucial role in the progression of the disease. While motility of individual cells is relatively well understood, little is known about the dynamics of N. gonorrhoeae aggregation. We investigate how individual N. gonorrhoeae cells, initially uniformly dispersed on flat plastic or glass surfaces, agglomerate into spherical microcolonies within hours. We quantify the clustering process by measuring the area fraction covered by the cells, number of cell aggregates, and their average size as a function of time. We observe that the microcolonies are also able to move but their mobility rapidly vanishes as the size of the colony increases. After a certain critical size they become immobile. We propose a simple theoretical model which assumes a pili-pili interaction of cells as the main clustering mechanism. Numerical simulations of the model quantitatively reproduce the experimental data on clustering and thus suggest that the agglomeration process can be entirely explained by the Tfp-mediated interactions. In agreement with this hypothesis mutants lacking pili are not able to form colonies. Moreover, cells with deficient quorum sensing mechanism show similar aggregation as the wild-type bacteria. Therefore, our results demonstrate that pili provide an essential mechanism for colony formation, while additional chemical cues, for example quorum sensing, might be of secondary importance. PMID- 26355969 TI - Treating Parry-Romberg Syndrome Using Three-Dimensional Scanning and Printing and the Anterolateral Thigh Dermal Adipofascial Flap. AB - BACKGROUND: As three-dimensional technology becomes more ubiquitous, many plastic surgical applications have emerged. The authors investigate a three-dimensional scanning and printing system for facial soft tissue reconstruction in conjunction with an anterolateral thigh dermal adipofascial flap for the treatment of Parry Romberg syndrome. METHODS: Seven patients with facial atrophy of the zygomatic, buccal, and mandibular areas were included. Three-dimensional scanning of each patient's face in conjunction was analyzed with computer-aided design (CAD) to quantify areas of facial asymmetry. Models were then created using three dimensional printing to map areas of soft tissue deficiency. Free anterolateral thigh (ALT) dermal adipofascial flaps were designed based on the three dimensional models of soft tissue deficiency. RESULTS: All flaps survived. One case had a postoperative hematoma. Six patients had restored facial symmetry. One patient required fat injections to obtain symmetry. No patients required revision surgery of their healed flaps for contouring. CONCLUSIONS: Three-dimensional laser scanning and three-dimensional printing in combination with a free ALT dermal adipofascial flap offer surgeons a precise means to reconstruct facial contour deformities. PMID- 26355970 TI - Speech Articulatory Characteristics of Individuals With Dentofacial Deformity. AB - PURPOSE: To analyze the speech articulatory characteristics of individuals with dentofacial deformities (DFD) and assess differences compared to individuals with dentofacial balance. METHODS: Sixty individuals participated, being 30 presenting DFD (19 with class III and 11 class II skeletal malocclusion, 18 women and 12 men, age group 18-40 years) and 30 individuals from a control group matched for gender and age. The assessment of the diadochokinesis (DDK) was evaluated using the emissions /pa/, /ta/, /ka/, /pataka/, and /i/. RESULTS: The individuals with DFD produced fewer emissions per second: at syllable "ka" and sequence "pataka" for the total of individuals; syllable "pa" and sequence "pataka" for women, individuals with class II and class III malocclusion. The parameters related to the irregularity of the cycles were higher for the group with DFD than for the control, as well as emission of the syllable "pa" for the total of individuals, group of class III malocclusion and women, during production of the syllables "ta" and "ka" for all individuals and group of class III and during emission of the vowel "i" for women. CONCLUSIONS: Differences regarding speed and stability of oral and laryngeal DDK were found among individuals with DFD compared with the control group. PMID- 26355971 TI - Mapping the Mandibular Lingula in Pierre Robin Sequence: A Guide to the Inverted L Osteotomy. AB - BACKGROUND AND PURPOSE: The inverted-L osteotomy for mandibular distraction in Pierre Robin sequence (PRS) is a useful technique for avoiding injury to the tooth root and inferior alveolar nerve. Identification of the lingula is understudied and may decrease iatrogenic complications. This study aims to map the position of the lingula in the micrognathic mandible and compare the location of the lingula in relative normal mandible. METHODS: This is a retrospective cohort study of symptomatic PRS patients. Three-dimensional CT scans were reviewed and the relative lingula position described. RESULTS: The study includes 11 PRS patients and 4 controls. The average measurements were overjet 9.99 (PRS) versus 4.28 mm (control) (P = 0.001), vertical ramus height 16.05 versus 23.04 mm (P = 0.003), and width 15.16 versus 20.67 mm (P = 003); horizontal ramus length 26.58 versus 40.62 mm (P = 0.001), gonial angle 132.64 degrees versus 123.5 degrees (P = 0.018); horizontal lingula position 7.25 versus 10.75 mm (P = 0.001), vertical position 9.02 versus 11.34 mm (P = 0.026). The ratio along the x axis in PRS was 0.44 versus 0.52 in controls (P = 0.138); along the y-axis, the ratio was 0.57 versus 0.49 (P = 0.078). CONCLUSIONS: Compared to normal controls, overjet is greater, vertical ramus height and widths are lesser, horizontal ramus length is lesser, and the gonial angle is greater in PRS patients. When analyzed as proportions along the height and width of the vertical ramus, there is no statistical difference (P > 0.05) in the position of the lingula between PRS patients and normal controls. PMID- 26355972 TI - A Practical Mandibular Setback Technique With No Rigid Fixation. PMID- 26355973 TI - Comparison of Intraoperative Blood Loss and Postoperative Pain After Two Different Anterior Mandibular Osteotomies. AB - PURPOSE: The aim of this study was to compare intraoperative blood loss and postoperative pain in patients undergoing 2 different procedures for the treatment of bimaxillary protrusion with chin deficiency: anterior subapical osteotomy (ASO) of the maxilla (ASO Mx), ASO of the mandible (ASO Md), and genioplasty (Gep); and ASO Mx, bilateral parasymphyseal osteotomy (BPsO) of the mandible (BPsO Md), and Gep. MATERIALS AND METHODS: A 10-cm visual analog scale (VAS) was used to evaluate postoperative pain >2 days in 32 patients who underwent orthognathic surgery. According to osteotomy of mandible, patients were divided into 2 groups: 15 in the ASO group and 17 in the BPsO group. Patient- and operation-related factors (age, blood loss, operation time, and pre and postoperative blood parameters) were assessed, and postoperative pain using VASs were compared between both groups. RESULTS: Patient- and operation-related factors showed no significant difference in both groups. Mean operation time and blood loss were 406.67 minutes and 388.67 mL in the ASO group, and 447.35 minutes and 365 mL in the BPsO group. Mean VAS scores on the first and second postoperative days were 3 and 1.4 cm in the ASO group, and 2.82 and 1.76 cm in the BPsO group, also indicating no significant between-group differences. CONCLUSION: Intraoperative blood loss and postoperative pain control following orthognathic surgery were within acceptable parameters, with no significant differences between the ASO and BPsO procedures. PMID- 26355974 TI - The Evaluation of Relationship Between Body Mass Index and Nasal Geometry Using Objective and Subjective Methods. AB - INTRODUCTION: It is known that obesity causes obstructive sleep apnea syndrome by increasing upper airway resistance. Also, obese patients are admitted to the ear, nose, and throat clinic very often because of nasal obstruction complaint. The aim of this study is to identify the change and relation among body mass index (BMI), nasal resistance, reduction in nasal ariflow, nasal anatomy, and patients' subjective complaints. MATERIAL AND METHOD: A total of 67 patients admitted to our clinic between August 2013 and January 2014 were included in the study.The study group comprised 33 patients who had a chief complaint-nasal obstruction and the other group consisted of 34 patients who had no complaint and nasal pathology. Both the groups were checked with acoustic rhinometry (AR), active anterior rhinomanometer, nasal obstruction symptom evaluation (NOSE), and visual analog study (VAS) questionnaire. RESULTS: There is a significant statistical correlation between the body mass increase and VAS and NOSE score increase (P < 0.05). But the authors did not find any statistically significant relation between BMI and total inspiratory and expiratory MR and MF measured by anterior active rhinomanometer and left and right nasal cavity MCA, and volume measured by acoustic rhinometery (P > 0.05). CONCLUSIONS: Contrary to belief, obesity does not change the nasal resistance, airflow, and anatomy but it can cause subjective nasal complaints. PMID- 26355975 TI - Cranioplasty of Hemispherical Defects Using High Impact Methylmethacrylic Plate. AB - Decompressive craniectomy is the most common neurosurgical procedure performed in today's scenario, usually posttrauma or a cerebrovascular event. Cranioplasty is the repair of a cranial defect or deformation. In the last decade, there has been an increase in the number of cranioplasties performed because of an increase in the number of decompressive craniectomies. Although the main purpose of cranioplasty is to protect the brain and restore aesthetics, it has been proved beyond doubt that there is also an improvement in function and patient self esteem.Reconstructing the skull after a decompressive craniectomy is a challenge because of the size and contour of the defect, the projection of the brain outside in many cases, and the attendant risks of infection, hematoma, seizures, and CSF leak. In the last few decades, an enormous array of biomaterials has been used for cranioplasty, but there is no consensus on the best material. Each has its own advantages and disadvantages. Polymethylmethacrylate has been used for cranioplasty since the World War II and is still the most widely used reconstructive material. MATERIALS AND METHODS: Patients requiring reconstruction of hemispherical cranial defects were taken up for the study. An impression of the defect was taken over the skin using impression compound first and then silicone impression material. The model was trimmed to size, and an acrylic plate was made from High Impact Acrylic. Under general anesthesia, the acrylic plate was fixed to the margins of the defect using titanium plates and screws. Suction drain was placed and the wound closed with Vicryl Rapid. All patients were followed up for 2 years to note any postoperative complications and change in neurological status. There were 12 male patients and 3 female patients. Age of the patients ranged between 8 and 55 years. RESULTS: All patients were happy with the aesthetic results. There were no complications in all our patients. A few patients showed dramatic improvement in their neurological status. CONCLUSION: High Impact Acrylic is an excellent restorative material for reconstructing large sized cranial defects. PMID- 26355976 TI - Occlusal Relations in Patients With Scaphocephaly. AB - Scaphocephaly results from a premature fusion of the sagittal suture. Usually, cranial vault corrective surgery is performed during the first year of life. There is currently no scientific data regarding occlusion of scaphocephalic patients, or the potential effect of craniovault surgery on the occlusion. The aims were to describe occlusion in scaphocephalic patients and compare with a general pediatric population, and to compare the difference in occlusion of surgically versus unoperated treated scaphocephalic subgroup. A total of 91 scaphocephalic patients (71 boys aged between 2 and 11 y) seen at the Craniofacial Clinic of CHU Ste-Justine's formed the experimental group. All patients received an orthodontic assessment. Among them, 44 underwent craniovault surgery, whereas 47 remained unoperated. Thirty-eight (33 boys; 17 operated) had lateral cephalometric radiographies, some of them also had cephalometric growth follow-ups. Clinical values for dental classification and overjet indicate an increased prevalence of class II malocclusions in scaphocephalic patients. However, interestingly enough, cephalometric values indicative of skeletal class II malocclusions (ie, N-A perp HP, N-B perp HP, N-Pog perp HP, Wits, N-A-Pog) remained within normal limits. Some cephalometric values present statistically significant differences between operated and unoperated patients (ANS-PNS t2, P = 0.025; /1-FH t2, P = 0.028), but these are individual variations not related to scaphocephaly. Maxillary width of scaphocephalic children remains within normal limits. Scaphocephalic patients clinically presented more class II malocclusions compared with normal children. Radiographic values remain, however, within normal limits for both anteroposterior and transverse dimensions. Corrective craniovault surgery did not affect occlusion in these patients. PMID- 26355977 TI - A New, Single-Stage, Distraction-Mediated, Cranial Vault Expansion Technique for the Multisuture Deformity. AB - Multisuture craniosynostosis with a mild cloverleaf deformity is rare but associated with high morbidity and mortality. Conventional treatment to alleviate intracranial hypertension in a young infant involves multisuturectomy and relies on passive correction of the deformity followed by additional staged reconstruction later in infancy. Early regional craniectomy and rigid reconstruction have been described, but the cranial bone has limited stability to tolerate plate fixation and extensive dissection of the bone-dura interface may devascularize the cranial bone flap and limit its durability. The authors report an interesting technique to treat a mild form of cloverleaf skull deformity using early, nondevascularizing osteotomies followed by application of semiburied cranial distractors in multiple planes to increase intracranial volume and treat the deformity, and its attendant volumetric constriction, in a single stage. PMID- 26355968 TI - Guideline for Care of Patients With the Diagnoses of Craniosynostosis: Working Group on Craniosynostosis. PMID- 26355978 TI - A Randomized Controlled Trial of Oral Versus Intravenous Administration of a Nonnarcotic Analgesia Protocol Following Pediatric Craniosynostosis Corrections on Nausea and Vomiting Rates. AB - BACKGROUND: The authors' center uses a nonnarcotic postoperative regimen following craniosynostosis corrections. Despite opioid avoidance, the authors noted that some children still experienced nausea and vomiting following the oral administration of either acetaminophen or ibuprofen. This study sought to evaluate whether intravenous administration of these medications might reduce nausea and vomiting rates. METHODS: A total of 50 children undergoing craniosynostosis corrections were prospectively randomized to a control group given only oral ibuprofen (10 mg/kg) and acetaminophen (15 mg/kg), or a treatment group given only intravenous ketorolac (0.5 mg/kg) and acetaminophen (15 mg/kg). All patients were assessed for postoperative nausea and vomiting by a blinded research nurse. RESULTS: Twenty-eight patients randomized to the oral control group, and 22 to the intravenous treatment group. No statistically significant differences were identified between groups, including: age, weight, sex, before history of severe postoperative nausea and vomiting, or procedure. With similar anesthesia times there was significantly more vomiting episodes in the oral group (71% versus 41%). Using a multivariate logistic regression, controlling for age, weight and procedure, the odds ratio for vomiting in the oral control versus intravenous experimental groups was 3.61 (95% CI 1.11-1.76; P = 0.033), and for postoperative nausea was 14.0 (95% CI 1.40-71.69, P = 0.010). CONCLUSIONS: The authors found a significant reduction in nausea and vomiting among children randomized to receive intravenous medications. In addition, the intravenous delivery of medications has the theoretical advantage of insuring an effective full dose delivery. Based on these findings, our standard process is to preferentially manage all children following craniosynostosis corrections with intravenous nonnarcotics. PMID- 26355979 TI - Subgaleal Drain Placement Improves Surgical Outcomes After Primary Cranioplasty in Craniosynostosis Patients. AB - BACKGROUND: There is no published data addressing the use of postoperative subgaleal drains in patients undergoing primary cranioplasty for craniosynostosis. We conducted a retrospective chart review in this population of patients, comparing outcomes of those who received postoperative drains with those who did not. We hypothesize that the subgaleal drains can significantly diminish postoperative facial edema and reduce the length of hospital stay. METHODS: We conducted a retrospective chart review of all patients undergoing primary cranioplasty for craniosynostosis with subgaleal drain placement (May 2010-March 2012). A comparison group without drain placement was matched appropriately to establish a comparison of outcomes. We determined whether subgaleal drainage led to improvement in postoperative facial edema, reduced length of hospital stay, postoperative changes in hematocrit (Hct), and complication rates. RESULTS: Of the 50 patients in this cohort, 25 patients had received subgaleal drains. The mean length of stay was 2.4 versus 3.5 days for the respective drained and undrained cohorts (P = 0.03). There was no significant difference in the mean decline in Hct between drained and undrained patients, with the mean Hct drop of 4.8% versus 5.0%, respectively (P = 0.83). Postoperative seroma formation developed in 3 undrained patients (17%) versus none in the drained cohort (0%). Although subjective, drained patients were observed to achieve quicker resolution of facial swelling and earlier recovery of eye opening. CONCLUSIONS: There is clinical benefit in subgaleal drain placement as earlier resolution of postoperative facial edema and a significantly shortened length of hospital stay was found among the drained cohort. Future studies warrant prospective clinical trials to establish the safety and efficacy of using subgaleal drains in cranial remodeling procedures of craniosynostosis. PMID- 26355980 TI - Introduction of "Papazian Pusher: " A Modified-Design Knot Pusher for Surgical Repair of Cleft Palates. AB - Tying sutures is an integral aspect of any surgery and reliable instruments are essential for hassle-free procedures including craniofacial surgeries. Knot pushers have been widely known for their application in various laparoscopic, arthroscopic, and anal surgeries. The literature reveals numerous articles pertaining to knot pushers, as well as improvements on existing designs. Nevertheless, no application of knot pushers in the surgical repair of cleft palates has been described. We describe a new knot pusher "Papazian Pusher" (PP) finely designed for application in oral surgeries in general and repair of cleft palates in particular. The instrument was used satisfactorily in repair of cleft palate surgeries and no complications were encountered. The PP was found, overall, to be easy to use, and helps in performing faster, stronger, smooth, and secure knots. PMID- 26355981 TI - Location of Pterygopalatine Fossa and its Relationships to the Structures in Sellar Region. AB - PURPOSE: The aim of this study is to locate pterygopalatine fossa (PPF) and the opening of its communicating canals by accessing the relationship between PFF and the endoscopic landmarks such as the tubercular recess (TR) and middle lowest point of sellar floor (SF) as well as analyze the relation between PPF and important structures such as internal carotid artery (ICA) and optic canal (OC). MATERIALS AND METHODS: Computer topographic angiography (CTA) images of 118 PPF regions were reviewed. The measurement was on coronal, sagittal, and axial planes after multiplanar reconstruction (MPR). The location of PPF and its relationship to the sphenoid sinus, ICA, and OC were studied. The communicating canals of PPF, which were related to the transsphenoid approach, were three-dimensionally measured by the stationary structures, such as the middle lowest point of SF, the sagittal midline, and the top and bottom wall of sphenoid sinus. RESULT: The posterior part of PPF was located by the middle lowest point of SF. The anterior opening of sphenopalatine foramen (SPF), pterygoid canal (PC), palatovaginal canal (PVC), and foramina rotundum (FR) have relative stationary position, which can be located by the landmarks of sellar region during the endoscopic surgery. CONCLUSIONS: Pterygopalatine fossa is related to numerous neurovascular structures. Accurate understanding of the radiologic anatomy of PPF is beneficial for the PPF disease diagnosis, the selection of treatment plan and the prognosis evaluation. PMID- 26355982 TI - Pediatric Orbital Depth and Growth: A Radiographic Analysis. AB - BACKGROUND: Orbital reconstruction requires knowledge of orbital depth in order to prevent optic nerve injury. Numerous analyses of adult orbital dimensions have been undertaken previously in order to characterize this measurement, including skull specimen and computerized tomography studies. However, there is a paucity of information regarding the pediatric orbit. METHODS: The authors used pediatric magnetic resonance imaging (MRI) studies in order to quantify the change in orbital depth in relationship to patient age, and to develop methods to estimate and calculate orbital depth for individual pediatric patients. MRIs of the head in normal pediatric patients were reviewed retrospectively. Orbital depths were measured and correlated with age and cephalometric dimensions. In a randomly selected subgroup of patients, measurements were repeated by an independent investigator to determine interobserver reliability. RESULTS: Measurements were obtained in 72 patients ranging from 3 months to 18 years of age (mean=7.8 years). There was a significant exponential relationship between orbital depth and patient age (r=0.81, F(2,69)=143.97, P<0.001). Depth increased more rapidly in the first 6 years of life, but leveled off in the early teen years toward a horizontal asymptote of approximately 45 mm. There was also a significant relationship between orbital depth and the sum of the biparietal width plus the anterior-posterior length (r=0.72, F(2,69)=87.44, P<0.0001). There was high interobserver reliability in measurements between 2 independent investigators (r=0.79, P<0.0001). CONCLUSION: In children, orbital depth increases predictably with rising age and increasing head size. Knowledge of this growth curve and the relationship between head size and orbital depth can complement careful surgical dissection to improve safety and efficacy in pediatric orbital reconstructions. PMID- 26355983 TI - Application of a Novel Semi-Automatic Technique for Determining the Bilateral Symmetry Plane of the Facial Skeleton of Normal Adult Males. AB - The accurate assessment of symmetry in the craniofacial skeleton is important for cosmetic and reconstructive craniofacial surgery. Although there have been several published attempts to develop an accurate system for determining the correct plane of symmetry, all are inaccurate and time consuming. Here, the authors applied a novel semi-automatic method for the calculation of craniofacial symmetry, based on principal component analysis and iterative corrective point computation, to a large sample of normal adult male facial computerized tomography scans obtained clinically (n = 32). The authors hypothesized that this method would generate planes of symmetry that would result in less error when one side of the face was compared to the other than a symmetry plane generated using a plane defined by cephalometric landmarks. When a three-dimensional model of one side of the face was reflected across the semi-automatic plane of symmetry there was less error than when reflected across the cephalometric plane. The semi automatic plane was also more accurate when the locations of bilateral cephalometric landmarks (eg, frontozygomatic sutures) were compared across the face. The authors conclude that this method allows for accurate and fast measurements of craniofacial symmetry. This has important implications for studying the development of the facial skeleton, and clinical application for reconstruction. PMID- 26355984 TI - Effect of Presurgical Positioning on Skull Shape in Sagittal Suture Synostosis. AB - PURPOSE: The aim of the this study was to describe changes in head circumference (HC) and cephalic index (CI) in children with sagittal suture synostosis before surgery, by putting the child to bed in supine position lying on the back of the head. MATERIALS AND METHODS: A total of 83 patients were scheduled for minimally invasive spring-assisted correction at age 5 to 6 months. At presentation, parents were advised to place their child in bed lying on the back of their head. Preoperative evaluation involved measurement of HC and CI. Head circumference was measured at 2 time points in 33 patients and the CI at 2 time points in 19 patients. RESULTS: Head circumference (in SD) decreased from 1.69 to 1.37 and the CI increased from 66 to 69. CONCLUSION: Before surgery, positioning patients with sagittal suture synostosis on the back of the head is a feasible and effective way of changing head shape. More research is needed to evaluate the postsurgical effects on the long term. PMID- 26355985 TI - Migration of an Accidentally Swallowed Thorn to Submandibular Gland. PMID- 26355986 TI - Multiple Subungual Pyogenic Granulomas Following Levothyroxine Treatment. AB - Pyogenic granulomas are benign vascular lesions that can result from a large number of etiological factors. Drugs are one etiological factor involved in pyogenic granuloma development. In this study we present our experience of multiple pyogenic granulomas following levothyroxine administration suggesting that levothyroxine hormone replacement therapy might play an important role in the formation of pyogenic granuloma. We also reviewed the literatures regarding drug-induced pyogenic granulomas. PMID- 26355987 TI - Sinonasal Leiomyoma With Estrogen Receptor Expression. AB - Leiomyoma is an extremely rare tumor in sinonasal area. The reason for this is due to minimal amount of the smooth muscle in the area. The origin of this tumor is not clear and its etiology has not been proven in the literature. A 58-year old woman who experienced nasal obstruction and epiphora visited our clinic. A huge mass was noted in right nasal cavity originating from the lacrimal bone area. The authors conducted endoscopic sinus surgery and obtained the specimen. Immunochemistry showed leiomyoma in the nasal cavity, which expressed estrogen receptor. There was no progesterone receptor expressed. The authors describe a sinonasal leiomyoma with estrogen receptors, not ever reported in previous article. PMID- 26355988 TI - Accurate Evaluation of Cone-Beam Computed Tomography to Volumetrically Assess Bone Grafting in Alveolar Cleft Patients. AB - OBJECTIVE: The aim of this study was to investigate the accuracy of cone-beam computed tomography (CBCT) to assess the volume of bone graft in alveolar cleft patients. MATERIALS AND METHODS: Twelve patients of unilateral alveolar cleft were included in this study. All patients were taken CBCT preoperative and 1 week postoperative. The digital imaging and communications in medicine (DICOM) files were imported into Simplant software and three-dimensional (3D) reconstruction of the alveolar defect was achieved. With 3D volumetric measurements module, the volume of alveolar cleft was calculated preoperatively. During operation, the syringe compression method was adopted to calculate the actual amount of bone graft. One week postoperative, CBCT scan was performed again to measure the bone volume grafted to the defect. The volumetric ratio of the syringe compression method to preoperative CBCT assessment and the volume difference between syringe compression method and postoperative CBCT assessment were analyzed to evaluate the accuracy of CBCT measurement. RESULTS: The 3D structure of the alveolar cleft and the boundary of bone graft was clear from CBCT images. The estimated volume of alveolar cleft by preoperative CBCT scans was 1.06 +/- 0.09 cm, and the actual amount of bone graft determined by the syringe compression method was 1.51 +/- 0.12 cm. The ratio between the latter to the former was 1.43 +/- 0.07. The calculated volume of bone graft by 1-week postoperative CBCT scans was 1.53 +/- 0.11 cm, with no significant difference compared with the actual amount of bone graft (P > 0.05). CONCLUSIONS: CBCT was an accurate measurement to calculate the volume of alveolar defect and bone graft in alveolar cleft patients. Preoperative scans could aid in quantitatively determining the bone amount needed to adequately fill the bone defect, and the postoperative scans give accurate follow up evaluation after surgery. PMID- 26355989 TI - Mandibular Reconstruction for a Neglected Langerhans Cell Histiocytosis by Using Free Osteocutaneous Fibula Flap. PMID- 26355990 TI - Fully Erupted Intranasal Tooth Mimicking Benign Tumor. PMID- 26355991 TI - Dental Implant Placement in Patients With Osteoporosis. PMID- 26355992 TI - A Fluorescent, Reagentless Biosensor for ATP, Based on Malonyl-Coenzyme A Synthetase. AB - A fluorescent reagentless biosensor for ATP has been developed, based on malonyl coenzyme A synthetase from Rhodopseudomonas palustris as the protein scaffold and recognition element. Two 5-iodoacetamidotetramethylrhodamines were covalently bound to this protein to provide the readout. This adduct couples ATP binding to a 3.7-fold increase in fluorescence intensity with excitation at 553 nm and emission at 575 nm. It measures ATP concentrations with micromolar sensitivity and is highly selective for ATP relative to ADP. Its ability to monitor enzymatic ATP production or depletion was demonstrated in steady-state kinetic assays in which ATP is a product or substrate, respectively. PMID- 26355993 TI - A mixed-crystal lanthanide zeolite-like metal-organic framework as a fluorescent indicator for lysophosphatidic acid, a cancer biomarker. AB - Two lanthanide zeolite-like metal-organic frameworks (Ln-ZMOFs) with rho topology, Tb-ZMOF and Eu-ZMOF, were constructed by self-assembly of a 4-connected lanthanide molecular building block and a bipyridine-dicarboxylate ligand. Varying the Tb(3+) and Eu(3+) ratio during synthesis afforded three mixed-crystal isostructural MZMOFs with variable Eu:Tb stoichiometry. Fluorescence studies revealed that a methanol suspension of one of these mixed crystals, MZMOF-3, exhibits selective detection of lysophosphatidic acid (LPA), a biomarker for ovarian cancer and other gynecologic cancers. Linear correlation between the integrated fluorescence intensity and the concentration of LPA was observed, enabling quantitative analysis of LPA in physiologically relevant ranges (1.4 43.3 MUM). MZMOF-3 therefore has the potential to act as a self-referencing and self-calibrating fluorescent indicator for LPA. PMID- 26355994 TI - Transfer accuracy of vinyl polysiloxane trays for indirect bonding. AB - OBJECTIVE: To elicit the magnitude, directional bias, and frequency of bracket positioning errors caused by the transfer of brackets from a dental cast to the patient's dentition in a clinical setting. MATERIALS AND METHODS: A total of 136 brackets were evaluated. The brackets were placed on dental casts and scanned using cone beam computed tomography (CBCT) to capture 3-D positioning data. The brackets were then transferred to the patient's dentition with an indirect bonding method using vinyl polysiloxane (VPS) trays and later scanned using CBCT to capture the final bracket positioning on the teeth. Virtual models were constructed from the two sets of scan data and digitally superimposed utilizing best-fit, surface-based registration. Individual bracket positioning differences were quantified using customized software. One-tailed t tests were used to determine whether bracket positioning was within limits of 0.5 mm in the mesiodistal, buccolingual, and vertical dimensions, and 2 degrees for torque, tip, and rotation. RESULTS: Individual bracket positioning differences were not statistically significant, indicating, in general, final bracket positions within the selected limits. Transfer accuracy was lowest for torque (80.15%) and highest for mesiodistal and buccolingual bracket placement (both 98.53%). There was a modest directional bias toward the buccal and gingival. CONCLUSION: Indirect bonding using VPS trays transfers the planned bracket position from the dental cast to the patient's dentition with generally high positional accuracy. PMID- 26355995 TI - Dynamic Analysis of Gene Expression in Rice Superior and Inferior Grains by RNA Seq. AB - Poor grain filling of inferior grains located on lower secondary panicle branch causes great drop in rice yield and quality. Dynamic gene expression patterns between superior and inferior grains were examined from the view of the whole transcriptome by using RNA-Seq method. In total, 19,442 genes were detected during rice grain development. Genes involved in starch synthesis, grain storage and grain development were interrogated in particular in superior and inferior grains. Of the genes involved in sucrose to starch transformation process, most were expressed at lower level in inferior grains at early filling stage compared to that of superior grains. But at late filling stage, the expression of those genes was higher in inferior grains and lower in superior grains. The same trends were observed in the expression of grain storage protein genes. While, evidence that genes involved in cell cycle showed higher expression in inferior grains during whole period of grain filling indicated that cell proliferation was active till the late filling stage. In conclusion, delayed expression of most starch synthesis genes in inferior grains and low capacity of sink organ might be two important factors causing low filling rate of inferior grain at early filling stage, and shortage of carbohydrate supply was a limiting factor at late filling stage. PMID- 26355996 TI - Sensitive and quantitative probe of molecular chirality with heterodyne-detected doubly resonant sum frequency generation spectroscopy. AB - Heterodyne-detected vibrationally electronically doubly resonant chiral sum frequency generation (HD-DR chiral SFG) spectroscopy has been developed for the study of chiral molecules with chromophores. The method enables us to detect and distinguish chiral molecules with high sensitivity and to obtain information on molecular vibrations. Strong enhancement due to the electronic resonance improves the sensitivity, and heterodyne detection ensures that the signal intensity is linear to the sample concentration. Detection of HD-DR chiral SFG signal from a dilute solution of binaphthol with 20 mM concentration and tens of nanometers thickness was demonstrated. Taking advantage of the enantiomer-dependent sign and linearity of the signal to the concentration, molecular concentrations and enantiomeric excesses were accurately evaluated. HD-DR chiral SFG is expected to have widespread application in the study of molecular chirality of thin films or samples of a very small quantity. PMID- 26355997 TI - Hypertension, a Neglected Disease in Rural and Urban Areas in Moramanga, Madagascar. AB - BACKGROUND: Hypertension is one of the main risk factors of cardiovascular diseases. In Madagascar, studies on hypertension in urban and rural communities are scarce. OBJECTIVES: The aim of this study was to determine the prevalence of hypertension and identify associated risk factors in adults living in a health and demographic system in Moramanga, Madagascar. METHODS: The study included people aged 15 years old and above living in a health and demographic system in Moramanga. A household census was performed in 2012 to enumerate the population in 3 communities in Moramanga. In addition to the questionnaire used in the initial census, a standardized questionnaire and blood pressure were taken twice after 5 and 10 minutes of rest. In urban areas, heights and weights were also measured to calculate the body mass index. RESULTS: There were 3621 and 4010 participants respectively in rural and urban areas. Prevalence of hypertension in rural population was 27.0% (IC95% [25.6-28.5]) and 29.7% (IC95% [28.3-31.1]) in urban population. Among hypertensive subjects, 1.7% (17/979) and 5.3% (64/1191) were on antihypertensive treatment for at least 1 month before the survey in rural and urban population, respectively. In rural areas, increasing age (65 years and older vs 18-25 years OR = 11.81, IC95% [7.79-18.07]), giving more than 3 positive responses to the usual risks factors of hypertension (OR = 1.67, IC95% [1.14-2.42]) and singles in comparison with married people (OR = 1.61, IC95% [1.20-2.17]) were associated to hypertension in a logistic regression model. In urban areas, increasing age (65 years and older vs 18-25 years OR = 37.54, IC95% [24.81-57.92]), more than 3 positive responses to the usual risks of hypertension (OR = 3.47, IC95% [2.58-4.67]) and obesity (OR = 2.45, IC95% [1.56-3.87]) were found as risk factors. CONCLUSION: Hypertension is highly prevalent in rural areas although it is significantly less treated. As a result, a major epidemic of cardiovascular diseases is at risk in Madagascar's progressively aging society. PMID- 26356000 TI - Error in Text. PMID- 26356001 TI - Incorrect Information and Error in Figure. PMID- 26356002 TI - Combined Hamartoma of the Retina and Retinal Pigment Epithelium Leading to the Diagnosis of Neurofibromatosis Type 2. PMID- 26356003 TI - Dislocated Crystalline Lens Mimicking Metastatic Endometrial Cancer. PMID- 26356004 TI - Silicone Oil Retention Sutures for Retinal Detachment Repair Following Traumatic Aniridia, Aphakia, and Ruptured Globe. PMID- 26356005 TI - Hypometabolic Lateral Recti Due to Bilateral Cranial Nerve VI Palsy. PMID- 26356006 TI - Genetic and epigenetic contributors to FSHD. AB - Facioscapulohumeral dystrophy (FSHD) is an autosomal dominant muscle disorder characterized by distinct chromatin changes including DNA hypomethylation of the D4Z4 macrosatellite repeat array on a disease-permissive 4qA allele and aberrant expression of the D4Z4-embedded DUX4 retrogene in skeletal muscle. Insufficient epigenetic repression of the D4Z4 repeat is the result of at least two different genetic mechanisms leading to two forms of disease, FSHD1 and FSHD2. In the case of FSHD1, a contraction of the D4Z4 repeat array is disease causing whereas FSHD2 is most often caused by mutations in the structural maintenance of chromosomes hinge domain 1 (SMCHD1) gene. Recent studies indicate that a combination of genetic and epigenetic factors that act on the D4Z4 repeat array determine the probability of DUX4 expression in skeletal muscle and disease penetrance and progression. PMID- 26356007 TI - Web-based tool for visualization of electric field distribution in deep-seated body structures and planning of electroporation-based treatments. AB - BACKGROUND: Treatments based on electroporation are a new and promising approach to treating tumors, especially non-resectable ones. The success of the treatment is, however, heavily dependent on coverage of the entire tumor volume with a sufficiently high electric field. Ensuring complete coverage in the case of deep seated tumors is not trivial and can in best way be ensured by patient-specific treatment planning. The basis of the treatment planning process consists of two complex tasks: medical image segmentation, and numerical modeling and optimization. METHODS: In addition to previously developed segmentation algorithms for several tissues (human liver, hepatic vessels, bone tissue and canine brain) and the algorithms for numerical modeling and optimization of treatment parameters, we developed a web-based tool to facilitate the translation of the algorithms and their application in the clinic. The developed web-based tool automatically builds a 3D model of the target tissue from the medical images uploaded by the user and then uses this 3D model to optimize treatment parameters. The tool enables the user to validate the results of the automatic segmentation and make corrections if necessary before delivering the final treatment plan. RESULTS: Evaluation of the tool was performed by five independent experts from four different institutions. During the evaluation, we gathered data concerning user experience and measured performance times for different components of the tool. Both user reports and performance times show significant reduction in treatment-planning complexity and time-consumption from 1-2 days to a few hours. CONCLUSIONS: The presented web-based tool is intended to facilitate the treatment planning process and reduce the time needed for it. It is crucial for facilitating expansion of electroporation-based treatments in the clinic and ensuring reliable treatment for the patients. The additional value of the tool is the possibility of easy upgrade and integration of modules with new functionalities as they are developed. PMID- 26356008 TI - Structure and Binding Energy of Double-Stranded A-DNA Mini-helices: Quantum Chemical Study. AB - A-DNA is thought to play a significant biological role in gene expression due to its specific conformation and binding features. In this study, double-stranded mini-helices (dA:dT)3 and (dG:dC)3 in A-like DNA conformation were investigated. M06-2X/6-31G(d,p) method has been utilized to identify the optimal geometries and predict physicochemical parameters of these systems. The results show the ability of the corresponding mini-helices to preserve their A-like conformation under the influences of solvent, charge, and Na(+) counterions. Presented structural and energetic data offer evidence that two steps of GG/CC or AA/TT are already enough to turn the DNA helix to generate different forms by favoring specific values of roll and slide at a local level. Our calculations support the experimentally known fact that AA/TT steps prefer the B-form over the A-ones, whereas GG/CC steps may be found in either the B- or A-form. The stability of mini-helices at the level of total energy analysis, DeltaEtotal((A-B)), is discussed. PMID- 26356009 TI - Rerouting electron transfer in molecular assemblies by redox-pair matching. AB - We demonstrate how the distance over which electron transfer occurs through organic materials can be controlled and extended. Coating of conductive surfaces with nanoscale layers of redox-active metal complexes allows the electrochemical addressing of distant layers that are otherwise electrochemically silent. Our materials can pass electrons selectively in directions that are determined by positioning of layers of metal complexes and the distances between them. These electron-transfer processes can be made dominantly uni- or bidirectional. The design involves 1) a set of isostructural metal complexes with different electron affinities, 2) a scalable metal-organic spacer, and 3) a versatile assembly approach that allows systematic variation of composition, structure, and electron transfer properties. We control the electrochemical communication between interfaces by the deposition sequence and the spacer length, therefore we are able to program the bulk properties of the assemblies. PMID- 26356011 TI - Trends in U.S. Pediatric Otolaryngology Fellowship Training. AB - IMPORTANCE: Interest in pediatric otolaryngology fellowship training is growing. The workforce implications of this growing interest are unclear and understudied. OBJECTIVES: To analyze trends in pediatric otolaryngology training, determine where fellows who graduated over the past 10 years are currently practicing, and test the hypothesis that graduates from Accreditation Council for Graduate Medical Education (ACGME)-accredited programs were more likely to have academic tertiary positions with faculty appointments. DESIGN, SETTING, AND PARTICIPANTS: We conducted a web-based analysis of pediatric otolaryngology fellowship graduates. The names of all 274 applicants who were matched to pediatric otolaryngology fellowships from May 31, 2003, to May 31, 2014, were obtained from the SF Match website. Accreditation status of each program for each match year was obtained from the ACGME website. We then performed an Internet search for the current practice location of each matched applicant. Analysis was conducted from January 1, 2015, to May 1, 2015. MAIN OUTCOMES AND MEASURES: Practice setting per year of fellowship match and accreditation status of program. RESULTS: For the 2003 to the 2014 match years, there was an increase from 5 to 22 accredited pediatric otolaryngology fellowship programs overall; simultaneously, the number of yearly matched applicants increased from 14 to 35. More graduates with ACGME accreditation practice at academic settings compared with graduates without ACGME accreditation although the difference was not statistically significant (67.1% vs. 50.7%; P = .15). Graduates from accredited programs, however, were significantly more likely to practice at a hospital-based setting compared with those from nonaccredited programs (81.7% vs. 65.5%; P = .003). Fellows trained in the last 10 years are relatively well distributed across the country. CONCLUSIONS AND RELEVANCE: The number of pediatric otolaryngology fellowship applicants as well as total number of matched applicants and ACGME-accredited positions has risen in the last 10 years. It appears that a higher proportion of fellows trained in accredited programs work in academic positions in hospital-based practices. The long-term effect on the pediatric otolaryngology workforce of training more fellows in accredited fellowships remains to be seen. PMID- 26356010 TI - Disruption in dopaminergic innervation during photoreceptor degeneration. AB - Dopaminergic amacrine cells (DACs) release dopamine in response to light-driven synaptic inputs, and are critical to retinal light adaptation. Retinal degeneration (RD) compromises the light responsiveness of the retina and, subsequently, dopamine metabolism is impaired. As RD progresses, retinal neurons exhibit aberrant activity, driven by AII amacrine cells, a primary target of the retinal dopaminergic network. Surprisingly, DACs are an exception to this physiological change; DACs exhibit rhythmic activity in healthy retina, but do not burst in RD. The underlying mechanism of this divergent behavior is not known. It is also unclear whether RD leads to structural changes in DACs, impairing functional regulation of AII amacrine cells. Here we examine the anatomical details of DACs in three mouse models of human RD to determine how changes to the dopaminergic network may underlie physiological changes in RD. By using rd10, rd1, and rd1/C57 mice we were able to dissect the impacts of genetic background and the degenerative process on DAC structure in RD retina. We found that DACs density, soma size, and primary dendrite length are all significantly reduced. Using a novel adeno-associated virus-mediated technique to label AII amacrine cells in mouse retina, we observed diminished dopaminergic contacts to AII amacrine cells in RD mice. This was accompanied by changes to the components responsible for dopamine synthesis and release. Together, these data suggest that structural alterations of the retinal dopaminergic network underlie physiological changes during RD. PMID- 26356012 TI - Emerging Role of Interleukin 22 in Hepatitis B Virus Infection: a Double-edged Sword. AB - Hepatitis B virus (HBV) infection remains a worldwide health problem, and is the major cause of hepatitis, liver cirrhosis, and hepatocellular carcinoma. The innate and adaptive immune responses of the HBV-infected host contribute greatly to the development and pathogenesis of chronic HBV infection, and often affect the efficacy of anti-HBV drugs. Interleukin (IL)-22 is a newly identified cytokine that is involved in the pathogenesis of liver disease, but its role in liver inflammation in patients with HBV infection remains controversial. In this report, we summarize the production and function of IL-22 in inflammatory environments, and review the current research into IL-22 biology in HBV infection. A better understanding of the intrahepatic microenvironments that directly influence the activity of IL-22 will be important for the development of new immunotherapeutic approaches that target IL-22-producing cells or IL-22 itself. PMID- 26356013 TI - Effects of dietary n-6/n-3 polyunsaturated fatty acid ratios on the mass, and histological and ultrastructures of liver, spleen and thymus of 70-day-old Yangzhou goslings. AB - The objective of this study was to determine the effects of dietary n-6/n-3 polyunsaturated fatty acid (PUFA) ratios on the organ indexes, and histological and ultrastructures of organs including liver, spleen and thymus in 70-day-old Yangzhou goslings. One-hundred and sixty 21-day-old Yangzhou goslings were randomly divided into 4 groups and fed 4 diets varying in the n-6/n-3 PUFA ratio from 3:1 up to 12:1. After 1-week acclimation, the feeding experiment lasted for 6 weeks. At the end of the experimental period, goslings were slaughtered and the liver, spleen and thymus were weighed, and their histological and ultrastructures were examined. The results showed that the organ indices in the 3:1 group were remarkably higher than in the other three groups, whereas the mitochondrial square did not differ among four groups. The histological and ultrastructures of the liver, spleen and thymus were not affected by the diets with the lower n-6/n 3 PUFA ratios (3:1 and 6:1). However, feeding diets with the higher n-6/n-3 PUFA ratios (9:1 and 12:1), the nuclear chromatin was concentrated and marginalized; the cell membrane was contracted inwardly and disrupted; the mitochondrial membrane was damaged to some degree. In conclusion, the diet containing higher content of n-3 PUFA might improve immune capacity of goslings the animal by accelerating the growth and maintaining cellular structures of organs like liver, spleen and thymus. PMID- 26356014 TI - Partitioning Biological Networks into Highly Connected Clusters with Maximum Edge Coverage. AB - A popular clustering algorithm for biological networks which was proposed by Hartuv and Shamir identifies nonoverlapping highly connected components. We extend the approach taken by this algorithm by introducing the combinatorial optimization problem Highly Connected Deletion, which asks for removing as few edges as possible from a graph such that the resulting graph consists of highly connected components. We show that Highly Connected Deletion is NP-hard and provide a fixed-parameter algorithm and a kernelization. We propose exact and heuristic solution strategies, based on polynomial-time data reduction rules and integer linear programming with column generation. The data reduction typically identifies 75 percent of the edges that are deleted for an optimal solution; the column generation method can then optimally solve protein interaction networks with up to 6,000 vertices and 13,500 edges within five hours. Additionally, we present a new heuristic that finds more clusters than the method by Hartuv and Shamir. PMID- 26356015 TI - Measure the Semantic Similarity of GO Terms Using Aggregate Information Content. AB - The rapid development of gene ontology (GO) and huge amount of biomedical data annotated by GO terms necessitate computation of semantic similarity of GO terms and, in turn, measurement of functional similarity of genes based on their annotations. In this paper we propose a novel and efficient method to measure the semantic similarity of GO terms. The proposed method addresses the limitations in existing GO term similarity measurement techniques; it computes the semantic content of a GO term by considering the information content of all of its ancestor terms in the graph. The aggregate information content (AIC) of all ancestor terms of a GO term implicitly reflects the GO term's location in the GO graph and also represents how human beings use this GO term and all its ancestor terms to annotate genes. We show that semantic similarity of GO terms obtained by our method closely matches the human perception. Extensive experimental studies show that this novel method also outperforms all existing methods in terms of the correlation with gene expression data. We have developed web services for measuring semantic similarity of GO terms and functional similarity of genes using the proposed AIC method and other popular methods. These web services are available at http://bioinformatics.clemson.edu/G-SESAME. PMID- 26356016 TI - Effect of Incomplete Lineage Sorting On Tree-Reconciliation-Based Inference of Gene Duplication. AB - In the tree reconciliation approach to infer the duplication history of a gene family, the gene (family) tree is compared to the corresponding species tree. Incomplete lineage sorting (ILS) gives rise to stochastic variation in the topology of a gene tree and hence likely introduces false duplication events when a tree reconciliation method is used. We quantify the effect of ILS on gene duplication inference in a species tree in terms of the expected number of false duplication events inferred from reconciling a random gene tree, which occurs with a probability predicted in coalescent theory, and the species tree. We computationally examine the relationship between the effect of ILS on duplication inference in a species tree and its topological parameters. Our findings suggest that ILS may cause non-negligible bias on duplication inference, particularly on an asymmetric species tree. Hence, when gene duplication is inferred via tree reconciliation or any other approach that takes gene tree topology into account, the ILS-induced bias should be examined cautiously. PMID- 26356017 TI - Detecting Protein Complexes Based on Uncertain Graph Model. AB - Advanced biological technologies are producing large-scale protein-protein interaction (PPI) data at an ever increasing pace, which enable us to identify protein complexes from PPI networks. Pair-wise protein interactions can be modeled as a graph, where vertices represent proteins and edges represent PPIs. However most of current algorithms detect protein complexes based on deterministic graphs, whose edges are either present or absent. Neighboring information is neglected in these methods. Based on the uncertain graph model, we propose the concept of expected density to assess the density degree of a subgraph, the concept of relative degree to describe the relationship between a protein and a subgraph in a PPI network. We develop an algorithm called DCU (detecting complex based on uncertain graph model) to detect complexes from PPI networks. In our method, the expected density combined with the relative degree is used to determine whether a subgraph represents a complex with high cohesion and low coupling. We apply our method and the existing competing algorithms to two yeast PPI networks. Experimental results indicate that our method performs significantly better than the state-of-the-art methods and the proposed model can provide more insights for future study in PPI networks. PMID- 26356018 TI - Fast Entropic Profiler: An Information Theoretic Approach for the Discovery of Patterns in Genomes. AB - Information theory has been used for quite some time in the area of computational biology. In this paper we present a pattern discovery method, named Fast Entropic Profiler, that is based on a local entropy function that captures the importance of a region with respect to the whole genome. The local entropy function has been introduced by Vinga and Almeida in , here we discuss and improve the original formulation. We provide a linear time and linear space algorithm called Fast Entropic Profiler ( FastEP), as opposed to the original quadratic implementation. Moreover we propose an alternative normalization that can be also efficiently implemented. We show that FastEP is suitable for large genomes and for the discovery of patterns with unbounded length. FastEP is available at http://www.dei.unipd.it/~ciompin/main/FastEP.html. PMID- 26356019 TI - A Segmentation-Based Method to Extract Structural and Evolutionary Features for Protein Fold Recognition. AB - Protein fold recognition (PFR) is considered as an important step towards the protein structure prediction problem. Despite all the efforts that have been made so far, finding an accurate and fast computational approach to solve the PFR still remains a challenging problem for bioinformatics and computational biology. In this study, we propose the concept of segmented-based feature extraction technique to provide local evolutionary information embedded in position specific scoring matrix (PSSM) and structural information embedded in the predicted secondary structure of proteins using SPINE-X. We also employ the concept of occurrence feature to extract global discriminatory information from PSSM and SPINE-X. By applying a support vector machine (SVM) to our extracted features, we enhance the protein fold prediction accuracy for 7.4 percent over the best results reported in the literature. We also report 73.8 percent prediction accuracy for a data set consisting of proteins with less than 25 percent sequence similarity rates and 80.7 percent prediction accuracy for a data set with proteins belonging to 110 folds with less than 40 percent sequence similarity rates. We also investigate the relation between the number of folds and the number of features being used and show that the number of features should be increased to get better protein fold prediction results when the number of folds is relatively large. PMID- 26356021 TI - Mining Gene Expression Data Focusing Cancer Therapeutics: A Digest. AB - An understanding towards genetics and epigenetics is essential to cope up with the paradigm shift which is underway. Personalized medicine and gene therapy will confluence the days to come. This review highlights traditional approaches as well as current advancements in the analysis of the gene expression data from cancer perspective. Due to improvements in biometric instrumentation and automation, it has become easier to collect a lot of experimental data in molecular biology. Analysis of such data is extremely important as it leads to knowledge discovery that can be validated by experiments. Previously, the diagnosis of complex genetic diseases has conventionally been done based on the non-molecular characteristics like kind of tumor tissue, pathological characteristics, and clinical phase. The microarray data can be well accounted for high dimensional space and noise. Same were the reasons for ineffective and imprecise results. Several machine learning and data mining techniques are presently applied for identifying cancer using gene expression data. While differences in efficiency do exist, none of the well-established approaches is uniformly superior to others. The quality of algorithm is important, but is not in itself a guarantee of the quality of a specific data analysis. PMID- 26356020 TI - Outlier Analysis and Top Scoring Pair for Integrated Data Analysis and Biomarker Discovery. AB - Pathway deregulation has been identified as a key driver of carcinogenesis, with proteins in signaling pathways serving as primary targets for drug development. Deregulation can be driven by a number of molecular events, including gene mutation, epigenetic changes in gene promoters, overexpression, and gene amplifications or deletions. We demonstrate a novel approach that identifies pathways of interest by integrating outlier analysis within and across molecular data types with gene set analysis. We use the results to seed the top-scoring pair algorithm to identify robust biomarkers associated with pathway deregulation. We demonstrate this methodology on pediatric acute myeloid leukemia (AML) data. We develop a biomarker in primary AML tumors, demonstrate robustness with an independent primary tumor data set, and show that the identified biomarkers also function well in relapsed pediatric AML tumors. PMID- 26356022 TI - Aligning and Clustering Patterns to Reveal the Protein Functionality of Sequences. AB - Discovering sequence patterns with variations unveils significant functions of a protein family. Existing combinatorial methods of discovering patterns with variations are computationally expensive, and probabilistic methods require more elaborate probabilistic representation of the amino acid associations. To overcome these shortcomings, this paper presents a new computationally efficient method for representing patterns with variations in a compact representation called Aligned Pattern Cluster (AP Cluster). To tackle the runtime, our method discovers a shortened list of non-redundant statistically significant sequence associations based on our previous work. To address the representation of protein functional regions, our pattern alignment and clustering step, presented in this paper captures the conservations and variations of the aligned patterns. We further refine our solution to allow more coverage of sequences via extending the AP Clusters containing only statistically significant patterns to Weak and Conserved AP Clusters. When applied to the cytochrome c, the ubiquitin, and the triosephosphate isomerase protein families, our algorithm identifies the binding segments as well as the binding residues. When compared to other methods, ours discovers all binding sites in the AP Clusters with superior entropy and coverage. The identification of patterns with variations help biologists to avoid time-consuming simulations and experimentations. (Software available upon request). PMID- 26356023 TI - Improving the Robustness of Local Network Alignment: Design and Extensive Assessment of a Markov Clustering-Based Approach. AB - The analysis of protein behavior at the network level had been applied to elucidate the mechanisms of protein interaction that are similar in different species. Published network alignment algorithms proved to be able to recapitulate known conserved modules and protein complexes, and infer new conserved interactions confirmed by wet lab experiments. In the meantime, however, a plethora of continuously evolving protein-protein interaction (PPI) data sets have been developed, each featuring different levels of completeness and reliability. For instance, algorithms performance may vary significantly when changing the data set used in their assessment. Moreover, existing papers did not deeply investigate the robustness of alignment algorithms. For instance, some algorithms performances vary significantly when changing the data set used in their assessment. In this work, we design an extensive assessment of current algorithms discussing the robustness of the results on the basis of input networks. We also present AlignMCL, a local network alignment algorithm based on an improved model of alignment graph and Markov Clustering. AlignMCL performs better than other state-of-the-art local alignment algorithms over different updated data sets. In addition, AlignMCL features high levels of robustness, producing similar results regardless the selected data set. PMID- 26356024 TI - Ligand-K* Sequence Elimination: A Novel Algorithm for Ensemble-Based Redesign of Receptor-Ligand Binding. AB - K* is rotamerically ensemble-based approach to compute the binding constant. However, its time-consuming feature limited its application. We present a novel algorithm that not only computes the partition function efficiently, but also avoids the exponential growth of execution time by iteratively pruning the sequence space until the sequence with highest affinity is identified. PMID- 26356025 TI - Protein Function Prediction with Incomplete Annotations. AB - Automated protein function prediction is one of the grand challenges in computational biology. Multi-label learning is widely used to predict functions of proteins. Most of multi-label learning methods make prediction for unlabeled proteins under the assumption that the labeled proteins are completely annotated, i.e., without any missing functions. However, in practice, we may have a subset of the ground-truth functions for a protein, and whether the protein has other functions is unknown. To predict protein functions with incomplete annotations, we propose a Protein Function Prediction method with Weak-label Learning (ProWL) and its variant ProWL-IF. Both ProWL and ProWL-IF can replenish the missing functions of proteins. In addition, ProWL-IF makes use of the knowledge that a protein cannot have certain functions, which can further boost the performance of protein function prediction. Our experimental results on protein-protein interaction networks and gene expression benchmarks validate the effectiveness of both ProWL and ProWL-IF. PMID- 26356026 TI - Spatial Quantification of Cytosolic Ca2+ Accumulation in Nonexcitable Cells: An Analytical Study. AB - Calcium ions act as messengers in a broad range of processes such as learning, apoptosis, and muscular movement. The transient profile and the temporal accumulation of calcium signals have been suggested as the two main characteristics in which calcium cues encode messages to be forwarded to downstream pathways. We address the analytical quantification of calcium temporal accumulation in a long, thin section of a nonexcitable cell by solving a boundary value problem. In these expressions we note that the cytosolic Ca(2+) accumulation is independent of every intracellular calcium flux and depends on the Ca(2+) exchange across the membrane, cytosolic calcium diffusion, geometry of the cell, extracellular calcium perturbation, and initial concentrations. In particular, we analyse the time-integrated response of cytosolic calcium due to i) a localised initial concentration of cytosolic calcium and ii) transient extracellular perturbation of calcium. In these scenarios, we conclude that i) the range of calcium progression is confined to the vicinity of the initial concentration, thereby creating calcium microdomains; and ii) we observe a low pass filtering effect in the response driven by extracellular Ca(2+) perturbations. Additionally, we note that our methodology can be used to analyse a broader range of stimuli and scenarios. PMID- 26356027 TI - Bio-Driven Cell Region Detection in Human Embryonic Stem Cell Assay. AB - This paper proposes a bio-driven algorithm that detects cell regions automatically in the human embryonic stem cell (hESC) images obtained using a phase contrast microscope. The algorithm uses both statistical intensity distributions of foreground/hESCs and background/substrate as well as cell property for cell region detection. The intensity distributions of foreground/hESCs and background/substrate are modeled as a mixture of two Gaussians. The cell property is translated into local spatial information. The algorithm is optimized by parameters of the modeled distributions and cell regions evolve with the local cell property. The paper validates the method with various videos acquired using different microscope objectives. In comparison with the state-of-the-art methods, the proposed method is able to detect the entire cell region instead of fragmented cell regions. It also yields high marks on measures such as Jacard similarity, Dice coefficient, sensitivity and specificity. Automated detection by the proposed method has the potential to enable fast quantifiable analysis of hESCs using large data sets which are needed to understand dynamic cell behaviors. PMID- 26356028 TI - Reply to why follow-back studies should be interpreted cautiously: The case of an HPV-negative cervical lesion. PMID- 26356029 TI - Prediction of Mortality in Pulmonary Embolism Based on Left Atrial Volume Measured on CT Pulmonary Angiography. AB - BACKGROUND: Preliminary reports suggest that a small left atrium (LA) is associated with severe acute pulmonary embolism (PE). This study used data derived from volumetric analyses of computed tomographic pulmonary angiography (CTPA) to investigate whether a reduced LA volume can predict adverse outcome in a large series of patients with acute PE. METHODS: We retrospectively analyzed 756 consecutive patients who received a diagnosis of acute PE by nongated CTPA between January 2007 and December 2010. Each CTPA was investigated with volumetric analysis software that automatically provides the volumes of the LA, right atrium, right ventricle, and left ventricle. A classification tree divided the cardiac chamber volumes and ratios into categories according to mortality. Cox regression assessed the association between these categories and 30-day mortality after adjustment for age, sex, and clinical background. RESULTS: The final study group consisted of 636 patients who had successful volumetric segmentation and complete outcome data. Eighty-four patients (13.2%) died within 30 days of PE diagnosis. There was a higher mortality rate among patients with an LA volume <=62 mL compared with those with an LA volume >62 mL (19.6% vs 8.9%, respectively; HR, 2.44; P < .001), a left ventricle volume <=67 mL (16.4% vs 8.3%; HR, 1.8; P = .024) and a right atrium/LA volume ratio >1.2 (17% vs 9.4%; HR, 2.1; P = .002). A reduced LA volume was the best predictor of adverse outcome. CONCLUSIONS: Decreased LA volume is associated with higher mortality and is the first among the various cardiac compartments to predict mortality in patients with acute PE. PMID- 26356031 TI - Status of basal-supported oral therapy in Chinese type 2 diabetic patients with inadequate glycemic control on oral anti-diabetic drugs. AB - BACKGROUND: Timely initiation and titration of basal insulin added on to oral anti-diabetic drugs contribute to better glycemic control. However, implementation of basal-supported oral therapy in China is not yet clear. This nationwide, prospective, 12-week observational study was designed to explore the current status of basal-supported oral therapy in patients with type 2 diabetes in China. METHODS: Type 2 diabetic patients with inadequate glycemic control on anti-diabetic drugs who were to start basal-supported oral therapy with insulin glargine at outpatient clinics were enrolled from 134 hospitals in China. Both the decision to initiate basal insulin and insulin dose adjustment were at the physician's discretion. Fasting plasma glucose (FPG) and haemoglobin A1c were measured, and the starting dose of insulin were recorded at baseline. Self monitored fasting capillary blood glucose and the adjusting dose of insulin were collected during the study. RESULTS: A total of 11,192 out of 13,259 enrolled patients finished the 12-week study. FPG and haemoglobin A1c at basal-supported oral therapy initiation were 11.2 mmol/L and 9.4%, respectively, with insulin glargine started at 0.190 IU/kg/day. Insulin dose was increased 1.8 IU in average within 12 weeks. Fifty-nine percent of the patients achieved fasting capillary blood glucose <= 7.0 mmol/L. More patients achieved the glucose target in the group with lower baseline FPG level. Notable geographical differences of physicians' treatment habits in the current management of basal-supported oral therapy were also observed. CONCLUSIONS: A great gap between everyday clinical practice and guidelines exists in China, reflected by the delayed initiation, slow dose titration and geographical differences of basal-supported oral therapy management. A concrete guideline of basal-supported oral therapy management is needed in the clinical application. PMID- 26356030 TI - Engineering the hematopoietic stem cell niche: Frontiers in biomaterial science. AB - Hematopoietic stem cells (HSCs) play a crucial role in the generation of the body's blood and immune cells. This process takes place primarily in the bone marrow in specialized 'niche' microenvironments, which provide signals responsible for maintaining a balance between HSC quiescence, self-renewal, and lineage specification required for life-long hematopoiesis. While our understanding of these signaling mechanisms continues to improve, our ability to engineer them in vitro for the expansion of clinically relevant HSC populations is still lacking. In this review, we focus on development of biomaterials-based culture platforms for in vitro study of interactions between HSCs and their local microenvironment. The tools and techniques used for both examining HSC-niche interactions as well as applying these findings towards controlled HSC expansion or directed differentiation in 2D and 3D platforms are discussed. These novel techniques hold the potential to push the existing boundaries of HSC cultures towards high-throughput, real-time, and single-cell level biomimetic approaches that enable a more nuanced understanding of HSC regulation and function. Their application in conjunction with innovative biomaterial platforms can pave the way for engineering artificial bone marrow niches for clinical applications as well as elucidating the pathology of blood-related cancers and disorders. PMID- 26356034 TI - Prefronto-cerebellar transcranial direct current stimulation improves visuospatial memory, executive functions, and neurological soft signs in patients with euthymic bipolar disorder. AB - OBJECTIVE: The aim of the study was to improve neuropsychological functioning of euthymic patients with bipolar disorder (BD) using transcranial direct current stimulation (tDCS) applied to cerebellar and prefrontal cortices. METHODS: Twenty five BD outpatients underwent prefrontal (anodal) and cerebellar (cathodal) tDCS for 3 consecutive weeks. All participants were assessed through the Rey Complex Figure Test delay and copy and the Neurological Examination Scale at baseline and after therapy with tDCS. RESULTS: After tDCS treatment, patients showed significant improvements in visuospatial memory tasks. Patients with worse baseline cognitive performances also showed a significant improvement in executive functioning tasks. Neurological Examination Scale total score and motor coordination subscale significantly improved. CONCLUSION: Prefrontal-excitatory and cerebellar-inhibitory stimulations in euthymic BD patients may lead to better neurocognitive performances. This improvement could result from the modulation of prefronto-thalamic-cerebellar circuit activity pattern, which can be disrupted in BD. PMID- 26356032 TI - CXCR4 in breast cancer: oncogenic role and therapeutic targeting. AB - Chemokines are 8-12 kDa peptides that function as chemoattractant cytokines and are involved in cell activation, differentiation, and trafficking. Chemokines bind to specific G-protein-coupled seven-span transmembrane receptors. Chemokines play a fundamental role in the regulation of a variety of cellular, physiological, and developmental processes. Their aberrant expression can lead to a variety of human diseases including cancer. C-X-C chemokine receptor type 4 (CXCR4), also known as fusin or CD184, is an alpha-chemokine receptor specific for stromal-derived-factor-1 (SDF-1 also called CXCL12). CXCR4 belongs to the superfamily of the seven transmembrane domain heterotrimeric G protein-coupled receptors and is functionally expressed on the cell surface of various types of cancer cells. CXCR4 also plays a role in the cell proliferation and migration of these cells. Recently, CXCR4 has been reported to play an important role in cell survival, proliferation, migration, as well as metastasis of several cancers including breast cancer. This review is mainly focused on the current knowledge of the oncogenic role and potential drugs that target CXCR4 in breast cancer. Additionally, CXCR4 proangiogenic molecular mechanisms will be reviewed. Strict biunivocal binding affinity and activation of CXCR4/CXCL12 complex make CXCR4 a unique molecular target for prevention and treatment of breast cancer. PMID- 26356035 TI - Multipotent mesenchymal stromal cells promote tumor growth in distinct colorectal cancer cells by a beta1-integrin-dependent mechanism. AB - Tumor-stroma interactions play an essential role in the biology of colorectal carcinoma (CRC). Multipotent mesenchymal stromal cells (MSC) may represent a pivotal part of the stroma in CRC, but little is known about the specific interaction of MSC with CRC cells derived from tumors with different mutational background. In previous studies we observed that MSC promote the xenograft growth of the CRC cell-line DLD1. In the present study, we aimed to analyze the mechanisms of MSC-promoted tumor growth using various in vitro and in vivo experimental models and CRC cells of different mutational status. MSC specifically interacted with distinct CRC cells and supported tumor seeding in xenografts. The MSC-CRC interaction facilitated three-dimensional spheroid formation in CRC cells with dysfunctional E-cadherin system. Stable knock-downs revealed that the MSC-facilitated spheroid formation depended on beta1-integrin in CRC cells. Specifically in alpha-catenin-deficient CRC cells this beta1 integrin-dependent interaction resulted in a MSC-mediated promotion of early tumor growth in vivo. Collagen I and other extracellular matrix compounds were pivotal for the functional MSC-CRC interaction. In conclusion, our data demonstrate a differential interaction of MSC with CRC cells of different mutational background. Our study is the first to show that MSC specifically compared to normal fibroblasts impact early xenograft growth of distinct alpha catenin deficient CRC cells possibly through secretion of extracellular matrix. This mechanism could serve as a future target for therapy and metastasis prevention. PMID- 26356036 TI - Buckled Tin Oxide Nanobelt Webs as Highly Stretchable and Transparent Photosensors. AB - Stretchable and transparent inorganic semiconductors play a key role for the next generation of wearable optoelectronics. Achieving stretchability in intrinsically rigid inorganic materials is far more challenging than in polymers and metals. Here, we present a low-cost and scalable strategy to engineer inorganic semiconductors into a buckling open-mesh configuration, by which extraordinary stretchability (~160%) as well as high optical transparency (>86% at 550 nm) can be realized simultaneously in SnO2 nanofiber webs. Moreover, the mechanical stretchability of SnO2 nanowebs can be further improved along with the optical transparency by precisely controlling the nanofiber density. The as-prepared freestanding nanowebs can be laminated onto curved surfaces by conformal contact. It is demonstrated that the fully exposed SnO2 nanowebs can be used as wearable UV photodetectors, showing reliable optoelectronic performance and remarkable tolerance to repeated complex deformations with body movements. PMID- 26356037 TI - Major depressive disorder, personality disorders, and coping strategies are independent risk factors for lower quality of life in non-metastatic breast cancer patients. AB - OBJECTIVE: Our aim was to identify risk factors for lower quality of life (QOL) in non-metastatic breast cancer patients. METHODS: Our study included 120 patients from the University Hospital Centers of Tours and Poitiers. This cross sectional study was conducted 7 months after patients' breast cancer diagnosis and assessed QOL (Quality of Life Questionnaire Core 30 = QLQ-C30), socio demographic characteristics, coping strategies (Brief-COPE), physiological and biological variables (e.g., initial tumor severity and types of treatment received), the existence of major depressive disorder (Mini International Neuropsychiatric Interview), and pain severity (Questionnaire de Douleur Saint Antoine). We assessed personality disorders 3 months after diagnosis (Vragenlijst voor Kenmerken van de Persoonlijkheid questionnaire). We used multiple linear regression models to determine which factors were associated with physical, emotional, and global QOL. RESULTS: Lower physical QOL was associated with major depressive disorder, younger age, a more severe initial tumor stage, and the use of the behavioral disengagement coping. Lower emotional QOL was associated with major depressive disorder, the existence of a personality disorder, a more severe pain level, higher use of self-blame, and lower use of acceptance coping strategies. Lower global QOL was associated with major depressive disorder, the existence of a personality disorder, a more severe pain level, higher use of self blame, lower use of positive reframing coping strategies, and an absence of hormone therapy. CONCLUSIONS: Lower QOL scores were more strongly associated with variables related to the individual's premorbid psychological characteristics and the manner in which this individual copes with the cancer (e.g., depression, personality, and coping) than to cancer-related variables (e.g., treatment types and cancer severity). Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26356039 TI - Hypothalamic-pituitary-adrenal axis dysregulation and cortisol activity in obesity: A systematic review. AB - BACKGROUND: Although there is substantial evidence of differential hypothalamic pituitary-adrenal (HPA) axis activity in both generalized and abdominal obesity, consistent trends in obesity-related HPA axis perturbations have yet to be identified. OBJECTIVES: To systematically review the existing literature on HPA activity in obesity, identify possible explanations for inconsistencies in the literature, and suggest methodological improvements for future study. DATA SOURCES: Included papers used Pubmed, Google Scholar, and the University of California Library search engines with search terms body mass index (BMI), waist to-hip ratio (WHR), waist circumference, sagittal diameter, abdominal versus peripheral body fat distribution, body fat percentage, DEXA, abdominal obesity, and cortisol with terms awakening response, slope, total daily output, reactivity, feedback sensitivity, long-term output, and 11beta-HSD expression. STUDY ELIGIBILITY CRITERIA: Empirical research papers were eligible provided that they included at least one type of obesity (general or abdominal), measured at least one relevant cortisol parameter, and a priori tested for a relationship between obesity and cortisol. RESULTS: A general pattern of findings emerged where greater abdominal fat is associated with greater responsivity of the HPA axis, reflected in morning awakening and acute stress reactivity, but some studies did show underresponsiveness. When examined in adipocytes, there is a clear upregulation of cortisol output (due to greater expression of 11beta-HSD1), but in hepatic tissue this cortisol is downregulated. Overall obesity (BMI) appears to also be related to a hyperresponsive HPA axis in many but not all studies, such as when acute reactivity is examined. LIMITATIONS: The reviewed literature contains numerous inconsistencies and contradictions in research methodologies, sample characteristics, and results, which partially precluded the development of clear and reliable patterns of dysregulation in each investigated cortisol parameter. CONCLUSIONS AND IMPLICATIONS: The literature to date is inconclusive, which may well arise from differential effects of generalized obesity vs. abdominal obesity or from modulators such as sex, sex hormones, and chronic stress. While the relationship between obesity and adipocyte cortisol seems to be clear, further research is warranted to understand how adipocyte cortisol metabolism influences circulating cortisol levels and to establish consistent patterns of perturbations in adrenal cortisol activity in both generalized and abdominal obesity. PMID- 26356038 TI - High-fructose diet during periadolescent development increases depressive-like behavior and remodels the hypothalamic transcriptome in male rats. AB - Fructose consumption, which promotes insulin resistance, hypertension, and dyslipidemia, has increased by over 25% since the 1970s. In addition to metabolic dysregulation, fructose ingestion stimulates the hypothalamic-pituitary-adrenal (HPA) axis leading to elevations in glucocorticoids. Adolescents are the greatest consumers of fructose, and adolescence is a critical period for maturation of the HPA axis. Repeated consumption of high levels of fructose during adolescence has the potential to promote long-term dysregulation of the stress response. Therefore, we determined the extent to which consumption of a diet high in fructose affected behavior, serum corticosterone, and hypothalamic gene expression using a whole-transcriptomics approach. In addition, we examined the potential of a high-fructose diet to interact with exposure to chronic adolescent stress. Male Wistar rats fed the periadolescent high-fructose diet showed increased anxiety-like behavior in the elevated plus maze and depressive-like behavior in the forced swim test in adulthood, irrespective of stress history. Periadolescent fructose-fed rats also exhibited elevated basal corticosterone concentrations relative to their chow-fed peers. These behavioral and hormonal responses to the high-fructose diet did not occur in rats fed fructose during adulthood only. Finally, rats fed the high-fructose diet throughout development underwent marked hypothalamic transcript expression remodeling, with 966 genes (5.6%) significantly altered and a pronounced enrichment of significantly altered transcripts in several pathways relating to regulation of the HPA axis. Collectively, the data presented herein indicate that diet, specifically one high in fructose, has the potential to alter behavior, HPA axis function, and the hypothalamic transcriptome in male rats. PMID- 26356040 TI - Digit ratio (2D:4D) and psychopathic traits moderate the effect of exogenous testosterone on socio-cognitive processes in men. AB - Recent evidence suggests that testosterone is negatively correlated with empathic processes in both men and women. Also, administration of testosterone to young women impairs socio-cognitive performance as assessed using the "Reading the Mind in the Eyes Task", especially among those exposed to elevated testosterone concentrations prenatally. However, the extent to which testosterone plays a similar causal role in socio-cognitive abilities in men is currently unknown. Here, using a crossover, double-blind, placebo-controlled, within-subject design, we investigated the extent to which a single administration of testosterone to healthy young men (N=30) would impair socio-cognitive abilities assessed using the "Reading the Mind in the Eyes Task" (RMET). Also, we investigated whether individual differences in 2D:4D ratio and psychopathic traits would moderate the effect of testosterone on task performance. Results indicated that testosterone administration on its own did not impair RMET performance. However, variability in both 2D:4D ratio and psychopathic traits moderated the effect of testosterone on task performance. Specifically, testosterone impaired RMET performance among individuals with relatively low (i.e., masculinized) 2D:4D ratio and among individuals scoring relatively low on the interpersonal/affective facet (i.e., Factor 1) of psychopathy. Our findings highlight the importance of considering theoretically- and empirically-based individual difference factors when attempting to characterize the neuroendocrine mechanisms underlying socio cognitive processes. PMID- 26356041 TI - Diurnal salivary cortisol, glycemia and insulin resistance: The multi-ethnic study of atherosclerosis. AB - Hypercortisolism is associated with insulin resistance (IR) and diabetes mellitus (DM); however, to our knowledge prior studies have not examined the association of diurnal cortisol curve features with measures of glycemia or IR in a population-based setting. Using log-transformed salivary cortisol data on 850 ethnically diverse men and women from the Multi-Ethnic Study of Atherosclerosis, we investigated the cross-sectional association of cortisol curve features with (1) glycemia in those with and without DM and (2) IR, in non-diabetic subjects. The log-transformed salivary cortisol curve features included wake-up cortisol, cortisol awakening response (CAR), early decline slope (30min to 2h post awakening), late decline slope (2h post-awakening to bedtime), overall decline slope (0min to bedtime, excluding 30min cortisol), bedtime cortisol and total area under the curve (AUC). Overall, following multivariable adjustment, among those with diabetes mellitus (DM), early decline slope, overall decline slope, bedtime cortisol, and AUC were significantly and positively associated with a 5.4% (95% CI: 1.3, 9.7), 54.7% (95% CI: 12.4, 112.9), 4.0% (95% CI: 1.6,6.4), and 6.8% (95% CI: 3.3,10.4) higher HbA1c per 1 unit increase in log cortisol feature, respectively. Cortisol curve features were not associated with HbA1c among non diabetic participants; however, wake-up cortisol and AUC were associated with a 8.2% lower (95% CI: -13.3,-2.7) and 7.9% lower (95% CI: -14.6, -0.6) log HOMA-IR, respectively. This was attenuated by adjustment for waist circumference. Among participants with DM, cortisol curve parameters suggestive of higher hypothalamic pituitary-adrenal (HPA) axis activity and dysfunction were associated with higher HbA1c. In non-diabetic participants, greater HPA activity was paradoxically associated with lower insulin resistance. PMID- 26356043 TI - Capability of NIPAM polymer gel in recording dose from the interaction of (10)B and thermal neutron in BNCT. AB - The capability of N-isopropylacrylamide (NIPAM) polymer gel to record the dose resulting from boron neutron capture reaction in BNCT was determined. In this regard, three compositions of the gel with different concentrations of (10)B were prepared and exposed to gamma radiation and thermal neutrons. Unlike irradiation with gamma rays, the boron-loaded gels irradiated by neutron exhibited sensitivity enhancement compared with the gels without (10)B. It was also found that the neutron sensitivity of the gel increased by the increase of concentration of (10)B. It can be concluded that NIPAM gel might be suitable for the measurement of the absorbed dose enhancement due to (10)B and thermal neutron reaction in BNCT. PMID- 26356042 TI - Breadth and age-dependency of relations between cortical thickness and cognition. AB - Recent advances in neuroimaging have identified a large number of neural measures that could be involved in age-related declines in cognitive functioning. A popular method of investigating neural-cognition relations has been to determine the brain regions in which a particular neural measure is associated with the level of specific cognitive measures. Although this procedure has been informative, it ignores the strong interrelations that typically exist among the measures in each modality. An alternative approach involves investigating the number and identity of distinct dimensions within the set of neural measures and within the set of cognitive measures before examining relations between the 2 types of measures. The procedure is illustrated with data from 297 adults between 20 and 79 years of age with cortical thickness in different brain regions as the neural measures and performance on 12 cognitive tests as the cognitive measures. The results revealed that most of the relations between cortical thickness and cognition occurred at a general level corresponding to variance shared among different brain regions and among different cognitive measures. In addition, the strength of the thickness-cognition relation was substantially reduced after controlling the variation in age, which suggests that at least some of the thickness-cognition relations in age-heterogeneous samples may be attributable to the influence of age on each type of measure. PMID- 26356044 TI - Monte Carlo based calibration of an air monitoring system for gamma and beta+ radiation. AB - Marinelli beaker systems are used to monitor the activity of radioactive samples. These systems are usually calibrated with water solutions and the determination of the activity in gases requires correction coefficients accounting for the different mass-thickness of the sample. For beta+ radionuclides the different distribution of the positrons annihilation points should be also considered. In this work a Monte Carlo simulation based on Geant4 is used to compute correction coefficients for the measurement of the activity of air samples. PMID- 26356046 TI - Energy profile of nanobody-GFP complex under force. AB - Nanobodies (Nbs)-the smallest known fully functional and naturally occuring antigen-binding fragments-have attracted a lot of attention throughout the last two decades. Exploring their potential beyond the current use requires more detailed characterization of their binding forces as those cannot be directly derived from the binding affinities. Here we used atomic force microscope to measure rupture force of the Nb-green fluorescent protein (GFP) complex in various pulling geometries and derived the energy profile characterizing the interaction along the direction of the pulling force. We found that-despite identical epitopes-the Nb binds stronger (41-56 pN) to enhanced GFP than to wild type GFP (28-45 pN). Measured forces make the Nb-GFP pair a potent reference for investigating molecular forces in living systems both in and ex vivo. PMID- 26356047 TI - Molecular dynamics simulation of temperature profile in partially hydrogenated graphene and graphene with grain boundary. AB - Temperature profile in graphene, graphene with grain boundary and vacancy defects and hydrogenated graphene with different percentage of H-atoms are determined using molecular dynamics simulation. We also obtained the temperature profile in a graphene nanoribbon containing two types of grain boundaries with different misorientation angles, theta=21.8 degrees and theta=32.2 degrees . We found that a temperature gap appears in the temperature profile of a graphene nanoribbon with a grain boundary at the middle. Moreover, we found that the temperature profile in the partially hydrogenated graphene varies with the percentage of hydrogens, i.e. the C:H ratio. Our results show that a grain boundary line in the graphene sheet can change the thermal transport through the system which might be useful for controlling thermal flow in nanostructured graphene. PMID- 26356048 TI - Changes in cardiopulmonary function in normal adults after the Rockport 1 mile walking test: a preliminary study. AB - [Purpose] The purpose of this study was to investigate the changes of cardiopulmonary function in normal adults after the Rockport 1 mile walking test. [Subjects and Methods] University students (13 males and 27 females) participated in this study. Before and after the Rockport 1 mile walking test, pulmonary function, respiratory pressure, and maximal oxygen uptake were measured. [Results] Significant improvements in forced vital capacity and maximal inspiratory pressure were observed after the Rockport 1 mile walking test in males, and significant improvements in forced vital capacity, forced expiratory volume at 1 s, maximal inspiratory pressure, and maximal expiratory pressure were observed after the Rockport 1 mile walking test in females. However, the maximal oxygen uptake was not significantly different. [Conclusion] Our findings indicate that the Rockport 1 mile walking test changes cardiopulmonary function in males and females, and that it may improve cardiopulmonary function in middle-aged and older adults and provide basic data on cardiopulmonary endurance. PMID- 26356049 TI - Protein docking using an ensemble of spin labels optimized by intra-molecular paramagnetic relaxation enhancement. AB - Paramagnetic NMR is a useful technique to study proteins and protein complexes and the use of paramagnetic relaxation enhancement (PRE) for this purpose has become wide-spread. PREs are commonly generated using paramagnetic spin labels (SLs) that contain an unpaired electron in the form of a nitroxide radical, with 1-oxyl-2,2,5,5-tetramethyl-2,5-dihydropyrrol-3-ylmethyl methane thiosulfonate (MTSL) being the most popular tag. The inherent flexibility of the SL causes sampling of several conformations in solution, which can be problematic as over- or underestimation of the spatial distribution of the unpaired electron in structural calculations will lead to errors in the distance restraints. We investigated the effect of this mobility on the accuracy of protein-protein docking calculations using intermolecular PRE data by comparing MTSL and the less mobile 3-methanesulfonilthiomethyl-4-(pyridin-3-yl)-2,2,5,5-tetramethyl-2,5 dihydro-1H-pyrrol-1-yloxyl (pyMTSL) on the dynamic complex of cytochrome c and cytochrome c peroxidase. No significant differences were found between the two SLs. Docking was performed using either single or multiple conformers and either fixed or flexible SLs. It was found that mobility of the SLs is the limiting factor for obtaining accurate solutions. Optimization of SL conformer orientations using intra-molecular PRE improves the accuracy of docking. PMID- 26356050 TI - Profiling Isokinetic Strength by Leg Preference and Position in Rugby Union Athletes. AB - CONTEXT: Muscle imbalances aid in the identification of athletes at risk for lower-extremity injury. Little is known regarding the influence that leg preference or playing position may have on lower-extremity muscle strength and asymmetry. PURPOSE: To investigate lower-extremity strength profiles in rugby union athletes and compare isokinetic knee- and hip-strength variables between legs and positions. METHODS: Thirty male academy rugby union athletes, separated into forwards (n = 15) and backs (n = 15), participated in this cross-sectional analysis. Isokinetic dynamometry was used to evaluate peak torque, angle of peak torque, and strength ratios of the preferred and nonpreferred legs during seated knee extension/flexion and supine hip extension/flexion at 60 degrees /s. RESULTS: Backs were older (ES = 1.6) but smaller in stature (ES = -0.47) and body mass (ES = -1.3) than the forwards. The nonpreferred leg was weaker than the preferred leg for forwards during extension (ES = -0.37) and flexion (ES = -0.21) actions and for backs during extension (ES = -0.28) actions. Backs were weaker at the knee than forwards in the preferred leg during extension (ES = -0.50) and flexion (ES = -0.66) actions. No differences were observed in strength ratios between legs or positions. Backs produced peak torque at longer muscle lengths in both legs at the knee (ES = -0.93 to -0.94) and hip (ES = -0.84 to -1.17) than the forwards. CONCLUSIONS: In this sample of male academy rugby union athletes, the preferred leg and forwards displayed superior strength compared with the nonpreferred leg and backs. These findings highlight the importance of individualized athletic assessments to detect crucial strength differences in male rugby union athletes. PMID- 26356051 TI - A novel 3D covalent organic framework membrane grown on a porous alpha-Al2O3 substrate under solvothermal conditions. AB - A novel approach to grow a 3D COF-320 membrane on a surface-modified porous alpha Al2O3 substrate is developed. A compact and uniform COF-320 membrane with a layer thickness of ~4 MUm is obtained. This is the first reported 3D COF functional membrane fabricated successfully on a common porous alpha-Al2O3 ceramic support. The gas permeation results indicate that the gas transport behavior is mainly governed by the predicted Knudsen diffusion process due to the large nanopores of 3D COF-320. PMID- 26356052 TI - [Sliding trasheal plasty in children under extracorporeal membrane oxygenation (first experience in Russia)]. AB - AIM: To improve the results of surgical treatment of children with extended tracheal stenosis. MATERIAL AND METHODS: Since 2013 slidingtrasheal plasty under extracorporeal membrane oxygenation was performed in 4 children aged 1 year 2 months - 4.5 years with extended tracheal stenosis in Children's City Clinical Hospital No13. Patients' weight was from 10,5 to 16 kg. Extended tracheal stenosis and complete cartilag inousrings were confirmed in all patients after peoperative survey. Indications for surgery were based on medical history data, the severity of respiratory failure and survey data. Sliding trasheal plasty by different approach esunder extracorporeal membrane oxygenation was applied in all patients. RESULTS: There were no intraoperative complications. In the study group 1 patient died in remote postoperative period after discharge due to deterioration of his condition caused by upper respiratory tract infection and acute respiratory failure. In immediate postoperative period 1 patient had pronounced growth of granulation tissue in the area of anastomosis followed laser photocoagulation and prolonged intubation. The average ICU-stay was 24 days, the duration of mechanical ventilation - 11 days. Follow-up carefor patients was conducted on terms of 4-6 and 12 months after surgery. In 2 patients moderate complaints of recurrent bronchitis without signs of respiratory insufficiency during 6-8 months postoperatively were observed. In one child complaints were completely absent. PMID- 26356053 TI - [Vacuum-therapy of postoperative sternomediastinitis]. AB - AIM: To estimate the results of sternomediastinitis management using vacuum therapy compared with conventional treatment of such wounds. MATERIAL AND METHODS: We have retrospectively analyzed data for the period from January 2007 to October 2014. The study enrolled 79 patients with infectious complication after cardiac surgery. All patients underwent coronary artery bypass grafting. The first group included 40 patients who received conventional therapy. The second group enrolled 39 patients in whom vacuum-therapy was applied. Patients were comparable in main characteristics. RESULTS: Mortality rate was significantly lower in vacuum-therapy group (2.5% vs. 15%, p=0.05). Similarly duration of hospital-stay in the 2nd group was 29+/-10 days, in the 1st group - 47+/-11 days (p<0.01). Incidence of sepsis and other complications was significantly higher in group of conventional treatment. CONCLUSION: Vacuum therapy for infectious complications after cardiac surgery provided good results including decrease of hospital-stay duration and mortality rate in comparison with conventional management of wounds. PMID- 26356054 TI - [Surgical treatment of aortic arch malformations in infants under cardiopulmonary bypass]. AB - AIM: To evaluate long-term results and the causes of complications in congenital obstructive pathology of the aortic arch. MATERIAL AND METHODS: Retrospective study enrolled 62 patients aged 55 +/- 14 days who underwent aortic arch surgery under cardiopulmonary bypass. It was compared two methods of aortic archplasty: use of xenopericardial material in group 1 and Rajasinghe's autoplastic method in group 2. RESULTS: Follow-up was 42 +/- 14 months. In the long-term recoarctation occurred in 7 (13.7%) cases including 6 (18.75%) patients in group 1 and one (3.3%) patient in group 2. Residual hypertension was observed in 12 (23.5%) cases including 10 (37%) patients in group 1 and 2 (8.3%) patients in group 2. Six (50%) patients receive antihypertensive therapy, 5 (41.6%) patients who receive antihypertensive drugs have persistent increase of blood pressure without evidence of anatomic aortic obstruction. Hypertensive response to functional tests was observed in one patient. CONCLUSIONS: Aortic arch reconstruction using autoplasty is associated with lower risk of recoarctationand residual hypertension compared with xenopericardial patch application. PMID- 26356055 TI - [The results of biliary reconstructions after liver fragments transplantation]. AB - AIM: To analyze the results of repeated reconstructions of choleresis after living related liver fragments transplantation. MATERIAL AND METHODS: The study included 268 recipients (145 women and 123 men) aged 5 months - 61 years (mean age 16,11 +/- 14,62 years) who underwent liver fragments transplantation in the department of liver transplantation of cad. B.V. Petrovskiy Russian Research Surgery Center from 1997 to 2012. Biliary reconstructions were performed at different terms after transplantation in 37 patients (13.81%). Complications followed repeated reconstructions, the initial conditions for biliary anastomosis formation during transplantation, the results of biliary reconstructions after transplantation were analyzed. RESULTS: In most cases despite the prevailing complications there is a combination of various biliary complications requiring biliary reconstruction. It was found that live rfragment used for transplantation, type of primary reconstruction of choler sis, number of bile ducts orifices of graft and biliary anastomoses do not demonstrate statistically significant effect on the incidence of post-transplant biliary reconstructions (p>0.05). Poor prognosis in patients with biliary complications required biliary reconstructionsis determined by the development of graft dysfunction. Early reconstruction before development of liver transplant dysfunction is necessary condition of successful treatment. In the case of graft dysfunction liver retransplantation is unique method of treatment. PMID- 26356056 TI - [Restoration and reconstruction of extrahepatic bile ducts in high strictures using enteric autotransplant of variable diameter]. AB - AIM: To develop technique incorporating favorable aspects of gastroenterostomy in common hepatic duct anastomosis, providing bile drainage into duodenum and preventing duodenobiliary reflux. MATERIAL AND METHODS: It is presented developed operations for high strictures of extrahepatic bile ducts using enteric autotransplant of variable diameter. RESULTS: Good remote postoperative results were observed in 10 survived patients. There were no recurrence of stricture, cholangitis and normal biochemical parameters were observed. It has been proved that suggested methods may be alternative to Roux-en-Y hepaticojejunostomy. PMID- 26356057 TI - [Methods of acute pancreatitis prevention after endoscopic transpapillary interventions]. AB - AIM: To optimize preventive methods of acute postoperative pancreatitis in endoscopic transpapillary interventions. MATERIAL AND METHODS: It is performed parallel unblinded randomized investigation. The first group included 98 patients who underwent endoscopic transpapillary interventions and thoracic epidural analgesia (TEA). The second group consisted of 97 patients in whom opiate analgesic intramuscularly and indomethacin per rectum were applied. RESULTS: Study revealed that acute pancreatitis has been diagnosed significantly more seldom in patients after TEA than in the second group (OR 0.22, CI 95%, 0.06 0.83). Thus in TEA-group pancreatitis was verified in 3.1% (3 of 98 patients), in the second group - in 12.4% (12 of 97 patients). Incidence of pancreatitis decreased from 23.3% (10 of 43) to 4.3% (2 of 46) among high risk patients (OR 0.15, 95% CI 0.03-0.75). CONCLUSION: TEA is effective and justified preventive method in patients with high risk of postoperative pancreatitis. In low risk patients use of indomethacin per rectum is preferred compared with TEA due to its invasiveness. PMID- 26356058 TI - [Transanal endoscopic microsurgery]. AB - AIM: To analyze the immediate and remote results of transanal endoscopic microsurgical intervantions and its role in treatment of rectal tumors. MATERIAL AND METHODS: The results of transanal endoscopic microsurgery in 56 patients with rectal tumors were studied. Adenoma and adenocarcinoma were observed in 45 (80%) and 11 (20%) patients respectively. Mean height of tumor lower edge placement was 8.6 +/- 0.3 cm from anus, mean diameter - 3.7 +/- 0.3 cm. All patients underwent full-layer resection of rectum. RESULTS: Postoperative complications were observed in 4 (7%) patients. There were no deaths. Transanal endoscopic microsurgery is modern, adequate and effective treatment of benign and early forms of malignant rectal tumors. It is associated with lower incidence of complications and recurrence under condition of careful selection of patients. Based on obtained results we recommend surgeons to apply this technique only in case of tumor placement below 10-11 cm from anus and tumor's diameter up to 3-4 cm to minimize risk of complications and recurrences. Full-layer resection of rectum is recommended in all cases of operations for benign tumors because of there is high risk of latent malignancy. PMID- 26356059 TI - [Laparoscopic diagnosis and treatment of acute early adhesive intestinal obstruction]. AB - AIM: To estimate the role of emergency laparoscopic interventions in diagnosis and treatment of acute early adhesive intestinal obstruction. MATERIAL AND METHODS: It is presented the results of diagnostic and curative laparoscopic interventions in 58 patients with suspected acute early adhesive intestinal obstruction after abdominal surgery. Complex clinical-instrumental, non-invasive diagnosis does not always reveal this complication in early postoperative period. Diagnostic laparoscopy was the most informative method to assess state of abdominal cavity, to establish and characterize acute early adhesive intestinal obstruction, to determine following treatment and choice of surgery in all patients. RESULTS: Diagnosis of intestinal obstruction was not confirmed in 15 (25.9%) patients based laparoscopic checkup. Acute early adhesive intestinal obstruction was established in 43 (74.1%) patients. Small intestine injuries were observed in 2 (4.5%) cases during laparoscopy. Contraindications to laparoscopic treatment of obstruction were determined in 18 (41.9%) patients in whom conventional operations were performed with complications and death in 7 (38.8%) and 3 (16.6%) cases respectively. Curative laparoscopy was applied in 23 (53.4%) patients with successful resolving of intestinal obstruction and complications in 19 (82.7%) and 4 (17.4%) cases respectively. PMID- 26356060 TI - [Actovegin in treatment of critical limb ischemia]. AB - The problem of distal occlusion of the lower limbs cannot be currently considered solved due to too large number (40%) of postoperative amputations. Only surgical way of disease management seems impossible. Thus multidisciplinary approach is necessary. AIM: To determine the effectiveness of actovegin in treatment of critical ischemia of lower extremities. MATERIAL AND METHODS: The study included 60 patients (34 men, 26 women, mean age - 69.5 +/- 7.2 years) with confirmed atherosclerosis obliterans (critical limb ischemia stage III-IV with necrotic processes within the toes). Patients in the control group (n=30) received standard medical therapy including pentoxifylline (15 ml), rheopolyglukin (400.0 ml), antiplatelet agents (in some cases with dual antiplatelet therapy), low molecular weight heparins in prophylactic doses, statins. In the main group (n=30) actovegin in a daily dose of 1200 mg intravenously for 15 days, followed by 1200 mg in tablet form (2 tablets 3 times per day) for 15 days was added. Primary, 15-, 30- and 60-day pain-free walking distance and microcirculation using polarography and laser Doppler imaging were assessed in all patients. Cytological and histological studies were applied for double control of therapy's effectiveness. The reliability of the results of microcirculation investigation was achieved using an index of regional tissue perfusion. RESULTS AND DISCUSSION: Statistically significant improvement of transcutaneous oxygen tension has not been received in the control group. In the main group therapy with actovegin improved skin perfusion 35% by the 15th day and activated microcirculation 12.8% followed by increased tissue oxygenation. CONCLUSIONS: Positive effect of actovegin on the development of collateral blood flow in patients with distal occlusion of the lower limbs is convincingly proven. PMID- 26356061 TI - [Bilateral endoscopic lumbar sympathectomy for chronic limb ischemia]. PMID- 26356062 TI - [Inferior vena cava injury in endoscopic lumbar sympathectomy]. PMID- 26356063 TI - The Optimal Body Size Index with Which to Determine Iodine Dose for Hepatic Dynamic CT: A Prospective Multicenter Study. AB - PURPOSE: To identify the body size parameter that exhibits the best correlation with aortic and hepatic enhancement at hepatic dynamic computed tomography (CT) in a large patient population enrolled in a multicenter study. MATERIALS AND METHODS: This prospective study was approved by the ethics committee of each of the 31 participating institutions where 1342 patients were enrolled between April 2012 and September 2013. All patients provided either written or oral informed consent. All patients underwent hepatic dynamic CT, which included preenhanced, hepatic arterial phase (HAP), and portal venous phase (PVP) scanning, performed with the routine scanning protocol of each institution. Changes in CT number (in Hounsfield units) per gram of iodine in the aorta (eA/I) and liver (eL/I) during HAP and PVP scanning were recorded for each patient. Hierarchical multivariate linear regression analysis was performed in which the outcome variable was either eA/I or eL/I; the independent variables were age, sex, one body size parameter (height, body weight, body mass index, lean body weight [LBW], or body surface area), and liver function (aspartate aminotransferase, albumin, and total bilirubin levels). A two-level hierarchical model in which patients were level 1 and the institution was level 2 was used. RESULTS: Hierarchical multivariate linear regression analysis revealed that in the population not stratified by sex, body size was significantly correlated with eA/I and eL/I (P < .001) and that LBW exhibited the strongest correlation with eA/I and eL/I (r = -0.561 and r = 0.601, respectively). Sex-stratified analysis showed that LBW was more strongly correlated with eA/I and eL/I in women (r = -0.779 and r = -0.948, respectively) than in men (r = -0.500 and r = -0.494, respectively) or in the nonstratified total population. CONCLUSION: Among body size parameters, LBW exhibited the strongest correlation with aortic and hepatic enhancement, especially in women. PMID- 26356064 TI - CT Image Contrast of High-Z Elements: Phantom Imaging Studies and Clinical Implications. AB - PURPOSE: To quantify the computed tomographic (CT) image contrast produced by potentially useful contrast material elements in clinically relevant imaging conditions. MATERIALS AND METHODS: Equal mass concentrations (grams of active element per milliliter of solution) of seven radiodense elements, including iodine, barium, gadolinium, tantalum, ytterbium, gold, and bismuth, were formulated as compounds in aqueous solutions. The compounds were chosen such that the active element dominated the x-ray attenuation of the solution. The solutions were imaged within a modified 32-cm CT dose index phantom at 80, 100, 120, and 140 kVp at CT. To simulate larger body sizes, 0.2-, 0.5-, and 1.0-mm-thick copper filters were applied. CT image contrast was measured and corrected for measured concentrations and presence of chlorine in some compounds. RESULTS: Each element tested provided higher image contrast than iodine at some tube potential levels. Over the range of tube potentials that are clinically practical for average-sized and larger adults-that is, 100 kVp and higher-barium, gadolinium, ytterbium, and tantalum provided consistently increased image contrast compared with iodine, respectively demonstrating 39%, 56%, 34%, and 24% increases at 100 kVp; 39%, 66%, 53%, and 46% increases at 120 kVp; and 40%, 72%, 65%, and 60% increases at 140 kVp, with no added x-ray filter. CONCLUSION: The consistently high image contrast produced with 100-140 kVp by tantalum compared with bismuth and iodine at equal mass concentration suggests that tantalum could potentially be favorable for use as a clinical CT contrast agent. PMID- 26356065 TI - Specific rehabilitation exercise for the treatment of patients with chronic low back pain. AB - [Purpose] To evaluate the efficacy of our special rehabilitation method for patients with low back pain (LBP). [Subjects and Methods] All participants (n=33) received at least five individual 30-minute therapy sessions per week using the INFINITY method((r)) and six group therapy sessions per week in a gymnasium and swimming pool, each lasting 30 minutes and including the INFINITY method((r)). The treatment lasted between four to seven weeks. Plantar function using a graphic method (computer plantography), graphical quantification of postural control during static standing (posturography), and pain were measured and evaluated before and after rehabilitation therapy. The INFINITY method((r)) is a special rehabilitation method for patients with musculoskeletal problems. The method focuses on stabilization and strengthening of the trunk, dorsal and abdominal muscles, including the deep stabilization system which is closely linked with diaphragmatic breathing. It teaches the central nervous system to control muscles more precisely. [Results] Plantar functions, postural control in the upright stance and pain of LBP patients were significantly improved by 4-7 weeks of rehabilitation treatment with the INFINITY method((r)). There were significant differences in all measured dependent variables of the patients between before and after treatment. [Conclusion] Rehabilitation therapy with the INFINITY method((r)) positively influences body stabilization and pain in patients with problems of the lumbar spine. This method presents a new improved approach (with enhanced effect) to rehabilitation therapy for LBP patients. PMID- 26356066 TI - Estimation of the Ideal Lumbar Lordosis to Be Restored From Spinal Fusion Surgery: A Predictive Formula for Chinese Population. AB - STUDY DESIGN: A prospective, cross-sectional study. OBJECTIVE: To determine the independent variables associated with lumbar lordosis (LL) and to establish the predictive formula of ideal LL in Chinese population. SUMMARY OF BACKGROUND DATA: Several formulas have been established in Caucasians to estimate the ideal LL to be restored for lumbar fusion surgery. However, there is still a lack of knowledge concerning the establishment of such predictive formula in Chinese population. METHODS: A total of 296 asymptomatic Chinese adults were prospectively recruited. The relationships between LL and variables including pelvic incidence (PI), age, sex, and body mass index were investigated to determine the independent factors that could be used to establish the predictive formula. For the validation of the current formula, other 4 reported predictive formulas were included. The absolute value of the gap between the actual LL and the ideal LL yielded by these formulas was calculated and then compared between the 4 reported formulas and the current one to determine its reliability in predicting the ideal LL. RESULTS: The logistic regression analysis showed that there were significant associations of LL with PI and age (R = 0.508, P < 0.001 for PI; R = 0.088, P = 0.03 for age). The formula was, therefore, established as follows: LL = 0.508 * PI - 0.088 * Age + 28.6. When applying our formula to these subjects, the gap between the predicted ideal LL and the actual LL was averaged 3.9 +/- 2.1 degrees , which was significantly lower than that of the other 4 formulas. CONCLUSION: The calculation formula derived in this study can provide a more accurate prediction of the LL for the Chinese population, which could be used as a tool for decision making to restore the LL in lumbar corrective surgery. LEVEL OF EVIDENCE: 3. PMID- 26356067 TI - Prediction of Curve Progression in Idiopathic Scoliosis: Validation of the Sanders Skeletal Maturity Staging System. AB - STUDY DESIGN: Retrospective case series. OBJECTIVE: This study aimed to validate the Sanders Skeletal Maturity Staging System and to assess its correlation to curve progression in idiopathic scoliosis. SUMMARY OF BACKGROUND DATA: The Sanders Skeletal Maturity Staging System has been used to predict curve progression in idiopathic scoliosis. This study intended to validate that initial study with a larger sample size. METHODS: We retrospectively reviewed 1100 consecutive patients with idiopathic scoliosis between 2005 and 2011. Girls aged 8 to 14 years (<2 yr postmenarche) and boys aged 10 to 16 years who had obtained at least 1 hand and spine radiograph on the same day for evaluation of skeletal age and scoliosis curve magnitude were followed to skeletal maturity (Risser stage 5 or fully capped Risser stage 4), curve progression to 50 degrees or greater, or spinal fusion. Patients with nonidiopathic curves were excluded. RESULTS: There were 161 patients: 131 girls (12.3 +/- 1.2 yr) and 30 boys (13.9 +/- 1.1 yr). The distribution of patients within Sanders stage (SS) 1 through 7 was 7, 28, 41, 45, 7, 31, and 2 patients, respectively; modified Lenke curve types 1 to 6 were 26, 12, 63, 5, 38, and 17 patients, respectively. All patients in SS2 with initial Cobb angles of 25 degrees or greater progressed, and patients in SS1 and SS3 with initial Cobb angles of 35 degrees or greater progressed. Similarly, all patients with initial Cobb angles of 40 degrees or greater progressed except those in SS7. Conversely, none of the patients with initial Cobb angles of 15 degrees or less or those in SS5, SS6, and SS7 with initial Cobb angles of 30 degrees or less progressed. Predictive progression of 67%, 50%, 43%, 27%, and 60% was observed for subgroups SS1/30 degrees , SS2/20 degrees , SS3/30 degrees , SS4/30 degrees , and SS6/35 degrees respectively. CONCLUSION: This larger cohort shows a strong predictive correlation between SS and initial Cobb angle for probability of curve progression in idiopathic scoliosis. LEVEL OF EVIDENCE: 3. PMID- 26356068 TI - Parasol Rib Deformity in Hypotonic Neuromuscular Scoliosis: A New Radiographical Definition and a Comparison of Short-term Treatment Outcomes With VEPTR and Growing Rods. AB - STUDY DESIGN: Retrospective review of 2 multicenter national databases, Growing Spine Study Group and Chest Wall and Spine Deformity. OBJECTIVE: To derive an objective measure of parasol rib deformity from spine radiographs and to compare efficacy of rib-based (vertical expandable prosthetic titanium rib (VEPTR)) versus spine-based growing rods ("GR") instrumentation to improve parasol rib deformity and pulmonary function. SUMMARY OF BACKGROUND DATA: Children with low tone neuromuscular scoliosis often develop collapse of the rib cage ("parasol rib deformity") that may be associated with poor pulmonary function. METHODS: We compared patients with hypotonic neuromuscular scoliosis treated by VEPTR or GR with greater than 1 year follow-up. Preoperative and final spine radiographs were assessed for parasol rib collapse, spine asymmetry, and thoracic deformity. Multivariable analysis was performed on these measurements to identify the best descriptor of parasol rib deformity. Using this measurement, the ability of VEPTR versus GR to control parasol rib deformity was then compared. Assisted ventilation rating (AVR) at preoperative and final follow-up was compared between the 2 groups. RESULTS: Twenty-three patients treated with VEPTR (average age 6.7 years, average f/u = 3.3 years) were compared with 22 patients treated with GR (average age 7.7 years, average f/u = 2.9 years). The equation Parasol Score = (T6 convex hemithoracic width/T6 concave hemithoracic width) * (T6 thoracic width/T12 thoracic width) was the most accurate descriptor rib collapse (AUC = 0.927). Parasol Score was correlated with AVR. Parasol Score did not change over time for the patients treated with GR, but had a tendency to worsen for patients treated with VEPTR. AVR did not change significantly in either group. Spine deformity was better corrected using GR. CONCLUSION: Parasol rib deformity, measured on x-ray by the metric = (T6 width convex hemithorax/T6 width concave hemithorax)*(T6 thoracic width/T12 thoracic width), did not improve after treatment with VEPTR or GR. AVR did not change significantly in either group. LEVEL OF EVIDENCE: 4. PMID- 26356070 TI - Epidemiology of Hepatitis B Virus Infection in China: Current Status and Challenges. AB - The prevalence of hepatitis B is high in China. Based on the National Disease Supervision Information Management System of China, the mean reported incidence of hepatitis B was 84.3 per 100,000 in China between 2005 and 2010. There are differences in population distribution based on region and ethnic group. Here, risk factors, virological characteristics, and prophylaxis of hepatitis B in China are reviewed. Although the prevalence of HBV infection is gradually declining, there are many challenges in HBV infection control, including higher prevalence in floating population, poor compliance of antiviral therapy, and high disease burden. PMID- 26356071 TI - A process to establish nutritional guidelines to address obesity: Lessons from Mexico. AB - In 2010, the Mexican government implemented a multi-sector agreement to prevent obesity. In response, the Ministries of Health and Education launched a national school-based policy to increase physical activity, improve nutrition literacy, and regulate school food offerings through nutritional guidelines. We studied the Guidelines' negotiation and regulatory review process, including government collaboration and industry response. Within the government, conflicting positions were evident: the Ministries of Health and Education supported the Guidelines as an effective obesity-prevention strategy, while the Ministries of Economics and Agriculture viewed them as potentially damaging to the economy and job generation. The food and beverage industries opposed and delayed the process, arguing that regulation was costly, with negative impacts on jobs and revenues. The proposed Guidelines suffered revisions that lowered standards initially put forward. We documented the need to improve cross-agency cooperation to achieve effective policymaking. The 'siloed' government working style presented a barrier to efforts to resist industry's influence and strong lobbying. Our results are relevant to public health policymakers working in childhood obesity prevention. PMID- 26356072 TI - Skin Abscess due to Serratia marcescens in an Immunocompetent Patient after Receiving a Tattoo. AB - The incidence of skin infections caused by Serratia marcescens is extremely low and such infections are typically observed in immunocompromised patients. The clinical manifestations of these infections include cellulitis, abscesses, fluctuant nodules, or granulomatous lesions. Infections caused by S. marcescens are very difficult to treat due to their resistance to many antibiotics, which often leads to specific and prolonged treatment. Infections after receiving a tattoo are very rare and are caused by unhygienic conditions or the inexperience of the tattooist. In this paper we present the case of a 32-year-old male with no comorbidity, who presented an abscess caused by S. marcescens in a area that was tattooed one month earlier. The case was resolved with surgery and antimicrobial therapy that was based on the antibiogram. To our knowledge, this is the first reported case of a S. marcescens skin infection following a tattoo, in the absence of immunosuppression. PMID- 26356074 TI - Helsinki experience on nonvitamin K oral anticoagulants for treating cervical artery dissection. AB - BACKGROUND: Cervical artery dissection (CeAD) patients with or without stroke are frequently treated with either antiplatelet agents or vitamin K antagonists (VKAs), but few data are reported on the use of nonvitamin K oral anticoagulants (NOACs). METHODS: Between November 2011 and January 2014, we recorded data from patients with a stroke due to vertebral (VAD) or internal carotid artery dissection (ICAD). Patients using oral anticoagulants were included in the study and were divided into two treatment groups: patients using NOACs and those using VKAs. Excellent outcome was defined on modified Rankin Scale (mRS) <=1 at 6 months. RESULTS: Of 68 stroke patients (67% male; median age 45 [39-53]), six (8.8%; two with VAD and four with ICAD) were treated with NOACs: three with direct thrombin inhibitor dabigatran and three with direct factor Xa inhibitor rivaroxaban. National Institutes of Health Stroke Scale score at baseline was 4 (3-7) in the NOAC versus 2 (1-7) in the VKA groups. Complete recanalization at 6 months was seen in most patients in the NOAC (n = 5; 83%) and VKA (n = 34; 55%) groups. All the patients using NOACs had mRS <=1 at 6 months and none had an intracerebral hemorrhage (ICH). In the VKA group most patients (n = 48; 77%) had mRS <=1, one patient (1.7%) had an ICH and one died. CONCLUSIONS: In this small, consecutive single-center patient sample treating ischemic stroke patients with CeAD with NOACs did not bring up safety concerns and resulted in similar, good outcomes compared to patients using VKAs. PMID- 26356079 TI - Complex Quantum Network Manifolds in Dimension d > 2 are Scale-Free. AB - In quantum gravity, several approaches have been proposed until now for the quantum description of discrete geometries. These theoretical frameworks include loop quantum gravity, causal dynamical triangulations, causal sets, quantum graphity, and energetic spin networks. Most of these approaches describe discrete spaces as homogeneous network manifolds. Here we define Complex Quantum Network Manifolds (CQNM) describing the evolution of quantum network states, and constructed from growing simplicial complexes of dimension d. We show that in d = 2 CQNM are homogeneous networks while for d > 2 they are scale-free i.e. they are characterized by large inhomogeneities of degrees like most complex networks. From the self-organized evolution of CQNM quantum statistics emerge spontaneously. Here we define the generalized degrees associated with the delta faces of the d-dimensional CQNMs, and we show that the statistics of these generalized degrees can either follow Fermi-Dirac, Boltzmann or Bose-Einstein distributions depending on the dimension of the delta-faces. PMID- 26356073 TI - EMT-Inducing Molecular Factors in Gynecological Cancers. AB - Gynecologic cancers are the unregulated growth of neoplastic cells that arise in the cervix, ovaries, fallopian tubes, uterus, vagina, and vulva. Although gynecologic cancers are characterized by different signs and symptoms, studies have shown that they share common risk factors, such as smoking, obesity, age, exposure to certain chemicals, infection with human immunodeficiency virus (HIV), and infection with human papilloma virus (HPV). Despite recent advancements in the preventative, diagnostic, and therapeutic interventions for gynecologic cancers, many patients still die as a result of metastasis and recurrence. Since mounting evidence indicates that the epithelial-mesenchymal transition (EMT) process plays an essential role in metastatic relapse of cancer, understanding the molecular aberrations responsible for the EMT and its underlying signaling should be given high priority in order to reduce cancer morbidity and mortality. PMID- 26356080 TI - Correction: Design and Validation of a Periodic Leg Movement Detector. AB - [This corrects the article DOI: 10.1371/journal.pone.0114565.]. PMID- 26356081 TI - Scale-Adjusted Metrics for Predicting the Evolution of Urban Indicators and Quantifying the Performance of Cities. AB - More than a half of world population is now living in cities and this number is expected to be two-thirds by 2050. Fostered by the relevancy of a scientific characterization of cities and for the availability of an unprecedented amount of data, academics have recently immersed in this topic and one of the most striking and universal finding was the discovery of robust allometric scaling laws between several urban indicators and the population size. Despite that, most governmental reports and several academic works still ignore these nonlinearities by often analyzing the raw or the per capita value of urban indicators, a practice that actually makes the urban metrics biased towards small or large cities depending on whether we have super or sublinear allometries. By following the ideas of Bettencourt et al. [PLoS ONE 5 (2010) e13541], we account for this bias by evaluating the difference between the actual value of an urban indicator and the value expected by the allometry with the population size. We show that this scale adjusted metric provides a more appropriate/informative summary of the evolution of urban indicators and reveals patterns that do not appear in the evolution of per capita values of indicators obtained from Brazilian cities. We also show that these scale-adjusted metrics are strongly correlated with their past values by a linear correspondence and that they also display crosscorrelations among themselves. Simple linear models account for 31%-97% of the observed variance in data and correctly reproduce the average of the scale-adjusted metric when grouping the cities in above and below the allometric laws. We further employ these models to forecast future values of urban indicators and, by visualizing the predicted changes, we verify the emergence of spatial clusters characterized by regions of the Brazilian territory where we expect an increase or a decrease in the values of urban indicators. PMID- 26356082 TI - Program Code Generator for Cardiac Electrophysiology Simulation with Automatic PDE Boundary Condition Handling. AB - Clinical and experimental studies involving human hearts can have certain limitations. Methods such as computer simulations can be an important alternative or supplemental tool. Physiological simulation at the tissue or organ level typically involves the handling of partial differential equations (PDEs). Boundary conditions and distributed parameters, such as those used in pharmacokinetics simulation, add to the complexity of the PDE solution. These factors can tailor PDE solutions and their corresponding program code to specific problems. Boundary condition and parameter changes in the customized code are usually prone to errors and time-consuming. We propose a general approach for handling PDEs and boundary conditions in computational models using a replacement scheme for discretization. This study is an extension of a program generator that we introduced in a previous publication. The program generator can generate code for multi-cell simulations of cardiac electrophysiology. Improvements to the system allow it to handle simultaneous equations in the biological function model as well as implicit PDE numerical schemes. The replacement scheme involves substituting all partial differential terms with numerical solution equations. Once the model and boundary equations are discretized with the numerical solution scheme, instances of the equations are generated to undergo dependency analysis. The result of the dependency analysis is then used to generate the program code. The resulting program code are in Java or C programming language. To validate the automatic handling of boundary conditions in the program code generator, we generated simulation code using the FHN, Luo-Rudy 1, and Hund-Rudy cell models and run cell-to-cell coupling and action potential propagation simulations. One of the simulations is based on a published experiment and simulation results are compared with the experimental data. We conclude that the proposed program code generator can be used to generate code for physiological simulations and provides a tool for studying cardiac electrophysiology. PMID- 26356083 TI - Carbon Isotope Composition of Nighttime Leaf-Respired CO2 in the Agricultural Pastoral Zone of the Songnen Plain, Northeast China. AB - Variations in the carbon isotope signature of leaf dark-respired CO2 (delta13CR) within a single night is a widely observed phenomenon. However, it is unclear whether there are plant functional type differences with regard to the amplitude of the nighttime variation in delta13CR. These differences, if present, would be important for interpreting the short-term variations in the stable carbon signature of ecosystem respiration and the partitioning of carbon fluxes. To assess the plant functional type differences relating to the magnitude of the nighttime variation in delta13CR and the respiratory apparent fractionation, we measured the delta13CR, the leaf gas exchange, and the delta13C of the respiratory substrates of 22 species present in the agricultural-pastoral zone of the Songnen Plain, northeast China. The species studied were grouped into C3 and C4 plants, trees, grasses, and herbs. A significant nocturnal shift in delta13CR was detected in 20 of the studied species, with the magnitude of the shift ranging from 10/00 to 5.80/00. The magnitude of the nighttime variation in delta13CR was strongly correlated with the daytime cumulative carbon assimilation, which suggests that variation in delta13CR were influenced, to some extent, by changes in the contribution of malate decarboxylation to total respiratory CO2 flux. There were no differences in the magnitude of the nighttime variation in delta13CR between the C3 and C4 plants, as well as among the woody plants, herbs and graminoids. Leaf respired CO2 was enriched in 13C compared to biomass, soluble carbohydrates and lipids; however the magnitude of enrichment differed between 8 pm and 4 am, which were mainly caused by the changes in delta13CR. We also detected the plant functional type differences in respiratory apparent fractionation relative to biomass at 4 am, which suggests that caution should be exercised when using the delta13C of bulk leaf material as a proxy for the delta13C of leaf-respired CO2. PMID- 26356084 TI - Measuring Meiotic Crossovers via Multi-Locus Genotyping of Single Pollen Grains in Barley. AB - The detection of meiotic crossovers in crop plants currently relies on scoring DNA markers in a segregating population or cytological visualization. We investigated the feasibility of using flow-sorted haploid nuclei, Phi29 DNA polymerase-based whole-genome-amplification (WGA) and multi-locus KASP-genotyping to measure meiotic crossovers in individual barley pollen grains. To demonstrate the proof of concept, we used 24 gene-based physically mapped single nucleotide polymorphisms to genotype the WGA products of 50 single pollen nuclei. The number of crossovers per chromosome, recombination frequencies along chromosome 3H and segregation distortion were analysed and compared to a doubled haploid (DH) population of the same genotype. The number of crossovers and chromosome wide recombination frequencies show that this approach is able to produce results that resemble those obtained from other methods in a biologically meaningful way. Only the segregation distortion was found to be lower in the pollen population than in DH plants. PMID- 26356085 TI - Drug delivery and therapeutic impact of extended-release acetylsalicylic acid. AB - Current treatment guidelines recommend once-daily, low-dose acetylsalicylic acid (ASA; aspirin) for secondary prevention of cardiovascular events. However, the anti-thrombotic benefits of traditional ASA formulations may not extend over a 24 h period, especially in patients at high risk for a recurrent cardiovascular event. A next-generation, extended-release ASA formulation (ER-ASA) has been developed to provide 24-h anti-thrombotic coverage with once-daily dosing. The pharmacokinetics of ER-ASA indicates slower absorption and prolonged ASA release versus immediate-release ASA, with a favorable safety profile. ER-ASA minimizes systemic ASA absorption and provides sustained antiplatelet effects over a 24-h period. PMID- 26356086 TI - Effect of Skin-to-Skin Holding on Stress in Mothers of Late-Preterm Infants: A Randomized Controlled Trial. AB - PURPOSE: To examine the effect of skin-to-skin care (SSC) on stress perception between mothers who provided SSC to their late-preterm born infants and mothers who provided blanket holding. DESIGN AND METHODS: This was a longitudinal 2-group randomized controlled trial of 40 infant-mother dyads recruited from a level 3 neonatal intensive care unit in the upper Midwest. OUTCOME MEASURE: Maternal stress was measured using the Parental Stressor: Neonatal Intensive Care Unit (PSS: NICU) scale pre- and post-SSC intervention. Demographic and other mother and infant covariates were extracted from medical records. Physiologic stability was measured by the Stability of the Cardiorespiratory System in Preterm Infants (SCRIP) score. Study personnel used daily logs to track frequency and duration of SSC and holding sessions. RESULTS: The intervention and the control groups had similar pre- (mean +/- standard deviation, 2.34 +/- 0.86 for SSC and 2.94 +/- 0.87 for holding) and post-intervention (mean +/- standard deviation, 2.55 +/- 0.95 for SSC and 2.78 +/- 0.90 for holding) overall stress scores. Hours of SSC holding positively correlated with the change in stress scores for the entire scale (r = 0.58; P = .001), and for infant appearance (r = 0.58; P = .001) and parent role alteration (r = 0.48; P = .02) subscales. This relationship remained significant after controlling for the infant's length of stay and SCRIP score. IMPLICATIONS FOR PRACTICE: Mothers who provide SSC may experience more stress related to a more facilitated progression in the mother and infant relationship. IMPLICATIONS FOR RESEARCH: The relationship between increased stress and the number of hours of SSC holding warrants further investigation. PMID- 26356087 TI - Modulation of reactivity in the cavity of liposomes promotes the formation of peptide bonds. AB - In living cells, reactions take place in membrane-bound compartments, often in response to changes in the environment. Learning how the reactions are influenced by this compartmentalization will help us gain an optimal understanding of living organisms at the molecular level and, at the same time, will offer vital clues on the behavior of simple compartmentalized systems, such as prebiotic precursors of cells and cell-inspired artificial systems. In this work we show that a reactive building block (an activated amino acid derivative) trapped in the cavity of a liposome is protected against hydrolysis and reacts nearly quantitatively with another building block, which is membrane-permeable and free in solution, to form the dipeptide. By contrast, when the activated amino acid is found outside the liposome, hydrolysis is the prevalent reaction, showing that the cavity of the liposomes promotes the formation of peptide bonds. We attribute this result to the large lipid concentration in small compartments from the point of view of a membrane-impermeable molecule. Based on this result, we show how the outcome of the reaction can be predicted as a function of the size of the compartment. The implications of these results on the behavior of biomolecules in cell compartments, abiogenesis, and the design of artificial cell-inspired systems are considered. PMID- 26356088 TI - Tyrosine-Specific Chemical Modification with in Situ Hemin-Activated Luminol Derivatives. AB - Tyrosine-specific chemical modification was achieved using in situ hemin activated luminol derivatives. Tyrosine residues in peptide and protein were modified effectively with N-methylated luminol derivatives under oxidative conditions in the presence of hemin and H2O2. Both single and double modifications of the tyrosine residue occurred in the reaction of angiotensin II with N-methylated luminol derivative 9. Tyrosine-specific chemical modification of the model protein bovine serum albumin (BSA) revealed that the surface-exposed tyrosine residues were selectively modified with 9. We succeeded in the functionalization of several proteins using azide-conjugated compound 18 using alkyne-conjugated probes by copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) or dibenzocyclooctyne (DBCO)-mediated copper-free click chemistry. This tyrosine-specific modification was orthogonal to conventional lysine modification by N-hydroxysuccinimide (NHS) ester, and dual functionalization by fluorescence modification of tyrosine residues and PEG modification of lysine residues was achieved without affecting the modification efficiency. PMID- 26356089 TI - Solid-Phase Synthesis of Duocarmycin Analogues and the Effect of C-Terminal Substitution on Biological Activity. AB - The duocarmycins are potent antitumor agents with potential for use in the development of antibody-drug conjugates (ADCs) as well as being clinical candidates in their own right. In this article, we describe the synthesis of a duocarmycin monomer (DSA) that is suitably protected for utilization in solid phase synthesis. The synthesis was performed on a large scale, and the resulting racemic protected Fmoc-DSA subunit was separated by supercritical fluid chromatography (SFC) into the single enantiomers; its application to solid-phase synthesis methodology gave a series of monomeric and extended duocarmycin analogues with amino acid substituents. The DNA sequence selectivity was similar to that in previous reports for both the monomeric and extended compounds. Substitution at the C-terminus of duocarmycin caused a decrease in antiproliferative activity for all of the compounds studied. An extended compound containing an alanine at the C-terminus was converted to the primary amide or to an extended structure containing a terminal tertiary amine, but this had no beneficial effects on biological activity. PMID- 26356090 TI - Re: Sodium Valproate-Induced Myopathy in a Child. PMID- 26356091 TI - Treatment Outcome in Depressed Latinos Predicted by Concomitant Psychosislike Symptoms. AB - We compared treatment response (>=50 decrease in Nine-Item Patient Health Questionnaire total score) among 24 Latinos with major depressive disorder, presenting with and without specific psychosislike symptoms: A, hearing noises or house sounds, B, hearing voices calling one's name, C, seeing fleeting visions such as shadows, and D, symptoms more likely to be truly psychotic (e.g., poorly defined and short-lasting voices [other than B], fleeting paranoid ideation, or fleeting ideas of reference). 18 subjects (75%) endorsed symptoms of cluster A, 12 (50%) of cluster B, 10 (31%) of cluster C, and 12 (50%) of cluster D. Only subjects who reported symptoms from the D cluster exhibited significantly unfavorable depressive outcomes (compared to those with absence of D symptoms). The authors propose a phenomenological differentiation between benign psychosislike symptoms (clusters A-C) and the expression of the psychotic continuum (cluster D) in depressed Latinos. PMID- 26356092 TI - Cognitive and Behavioral Factors Associated With Insomnia in Inpatients With Schizophrenia and Related Psychoses. AB - This study examines cognitive and behavioral factors linked to insomnia in individuals with schizophrenia and other psychotic disorders (with and without insomnia) and healthy controls (with and without insomnia). Fifty-five psychiatric inpatients and 66 healthy controls (n = 25 with insomnia in both groups) completed the Insomnia Severity Index, Thought Control Questionnaire for Insomnia-Revised, Dysfunctional Beliefs and Attitudes about Sleep scale, Sleep Hygiene Knowledge scale, and Beliefs about Causes of Sleep Problems questionnaires. Both insomnia groups demonstrated night-time rumination, aggressive suppression as a thought control strategy, and exaggerated views regarding the health consequences of poor sleep. In addition, the psychiatric group with insomnia frequently reported the causes of insomnia to be related to their illness (rather than to their lifestyle factors) and had an incomplete understanding of good sleep habits. Psychological interventions should be more commonly pursued as a first line of treatment for insomnia in schizophrenia and psychosis, and these should be adapted to address the unique knowledge gaps and cognitive style of patients. PMID- 26356093 TI - Metal-insulator crossover in multilayered MoS2. AB - The temperature dependence of electrical transport properties was investigated for multilayered MoS2 field effect transistor devices with thicknesses of 3-22 nm. Some devices showed typical n-type semiconducting behavior, while others exhibited metal-insulator crossover (MIC) from metallic to insulating conduction at finite temperatures. The latter effect occurred near zero gate voltage or at high positive gate voltages. Analysis of Raman spectroscopy revealed the key difference that devices with MIC have a metallic 1T phase as well as a semiconducting 2H phase, whereas devices without the MIC did not have a metallic 1T phase. These results suggest that the metallic 1T phase may contribute to inducing the MIC. PMID- 26356094 TI - Critically Ill Children Have Low Vitamin D-Binding Protein, Influencing Bioavailability of Vitamin D. AB - RATIONALE: Vitamin D deficiency, often defined by total serum 25-hydroxyvitamin D (25[OH]D) <20 ng/ml, is common in critically ill patients, with associations with increased mortality and morbidity in the intensive care unit. Correction of vitamin D deficiency in critical illness has been recommended, and ongoing clinical trials are investigating the effect of repletion on patient outcome. The biologically active amount of 25(OH)D depends on the concentration and protein isoform of vitamin D-binding protein (VDBP), which is also an acute-phase reactant affected by inflammation and injury. OBJECTIVES: We performed a secondary analysis of a cohort of critically ill children in which we reported a high rate of vitamin D deficiency, to examine how VDBP level and genotype would impact vitamin D status. METHODS: We prospectively enrolled 511 children admitted to the pediatric intensive care unit over a 12-month period. MEASUREMENTS AND MAIN RESULTS: We measured serum VDBP in 479 children. We genotyped single nucleotide polymorphisms rs7041 and rs4588 in the VDBP gene (GC) to determine haplotypes GC1F, GC1S, and GC2 in 178 subjects who consented, then calculated bioavailable 25(OH)D from serum 25(OH)D, VDBP, albumin, and GC haplotype. The median serum VDBP level was 159 MUg/ml (interquartile range, 108-221), lower than has been reported in healthy children. Factors predicting lower levels in multivariate analysis included age <1 year, nonwhite race, being previously healthy, 25(OH)D <20 ng/ml and greater illness severity. In the subgroup that was genotyped, GC haplotype had the strongest association with VDBP level; carriage of one additional copy of GC1S was associated with a 37.5% higher level (95% confidence interval, 31.9-44.8; P < 0.001). Bioavailable 25(OH)D was also inversely associated with illness severity (r = -0.24, P < 0.001), and ratio to measured total 25(OH)D was variable and related to haplotype. CONCLUSIONS: Physiologic deficiency of 25(OH)D in critical illness may be more difficult to diagnose, given that lower VDBP levels increase bioavailability. Treatment studies conducted on the basis of total 25(OH)D level, without consideration of VDBP concentration and genotype, may increase the risk of falsely negative results. PMID- 26356095 TI - Mallard or chicken? Comparing the isolation of avian influenza A viruses in embryonated Mallard and chicken eggs. AB - BACKGROUND: To date, the most efficient and robust method for isolating avian influenza A viruses (IAVs) is using embryonated chicken eggs (ECEs). It is known that low-pathogenic avian IAVs undergo rapid genetic changes when introduced to poultry holdings, but the factors driving mutagenesis are not well understood. Despite this, there is limited data on the effects of the standard method of virus isolation of avian-derived viruses, that is, whether isolation in ECEs causes adaptive changes in avian IAVs. Eggs from a homologous species could potentially offer an isolation vessel less prone to induce adaptive changes. METHODS: We performed eight serial passages of two avian IAVs isolated from fecal samples of wild Mallards in both ECEs and embryonated Mallard eggs, and hemagglutination assay titers and hemagglutinin sequences were compared. RESULTS: There was no obvious difference in titers between ECEs and embryonated Mallard eggs. Sequence analyses of the isolates showed no apparent difference in the rate of introduction of amino acid substitutions in the hemagglutinin gene (three substitutions in total in embryonated Mallard eggs and two substitutions in ECEs). CONCLUSION: Embryonated Mallard eggs seem to be good isolation vessels for avian IAVs but carry some practical problems such as limited availability and short egg-laying season of Mallards. Our study finds isolation of Mallard-derived avian IAVs in ECEs non-inferior to isolation in embryonated Mallard eggs, but more research in the area may be warranted as this is a small-scale study. PMID- 26356097 TI - NMR method for accurate quantification of polysorbate 80 copolymer composition. AB - (13)C NMR spectroscopic integration employing short relaxation delays and a 30 degrees pulse width was evaluated as a quantitative tool for analyzing the components of polysorbate 80. (13)C NMR analysis revealed that commercial polysorbate 80 formulations are a complex oligomeric mixture of sorbitan polyethoxylate esters and other intermediates, such as isosorbide polyethoxylate esters and poly(ethylene glycol) (PEG) esters. This novel approach facilitates the quantification of the component ratios. In this study, the ratios of the three major oligomers in polysorbate 80 were measured and the PEG series was found to be the major component of commercial polysorbate 80. The degree of polymerization of -CH2CH2O- groups and the ratio of free to bonded -CH2CH2O- end groups, which correlate with the hydrophilic/hydrophobic nature of the polymer, were analyzed, and were suggested to be key factors for assessing the likelihood of adverse biological reactions to polysorbate 80. The (13)C NMR data suggest that the feed ratio of raw materials and reaction conditions in the production of polysorbate 80 are not well controlled. Our results demonstrate that (13)C NMR is a universal, powerful tool for polysorbate analysis. Such analysis is crucial for the synthesis of a high-quality product, and is difficult to obtain by other methods. PMID- 26356096 TI - Environmental dissemination of antibiotic resistance genes and correlation to anthropogenic contamination with antibiotics. AB - Antibiotic resistance is a growing problem which threatens modern healthcare globally. Resistance has traditionally been viewed as a clinical problem, but recently non-clinical environments have been highlighted as an important factor in the dissemination of antibiotic resistance genes (ARGs). Horizontal gene transfer (HGT) events are likely to be common in aquatic environments; integrons in particular are well suited for mediating environmental dissemination of ARGs. A growing body of evidence suggests that ARGs are ubiquitous in natural environments. Particularly, elevated levels of ARGs and integrons in aquatic environments are correlated to proximity to anthropogenic activities. The source of this increase is likely to be routine discharge of antibiotics and resistance genes, for example, via wastewater or run-off from livestock facilities and agriculture. While very high levels of antibiotic contamination are likely to select for resistant bacteria directly, the role of sub-inhibitory concentrations of antibiotics in environmental antibiotic resistance dissemination remains unclear. In vitro studies have shown that low levels of antibiotics can select for resistant mutants and also facilitate HGT, indicating the need for caution. Overall, it is becoming increasingly clear that the environment plays an important role in dissemination of antibiotic resistance; further studies are needed to elucidate key aspects of this process. Importantly, the levels of environmental antibiotic contamination at which resistant bacteria are selected for and HGT is facilitated at should be determined. This would enable better risk analyses and facilitate measures for preventing dissemination and development of antibiotic resistance in the environment. PMID- 26356098 TI - A Systematic Critical Appraisal of Clinical Practice Guidelines in Juvenile Idiopathic Arthritis Using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) Instrument. AB - OBJECTIVES: The objectives of this review are to: 1) appraise the methodological quality of clinical practice guidelines (CPGs) in juvenile idiopathic arthritis (JIA) providing pharmacological and/or non-pharmacological intervention recommendations, and 2) summarize the recommendations provided by the included CPGs and compare them where possible. METHODS: A systematic search was performed. Three trained appraisers independently evaluated the methodological quality of the CPGs using a validated and reliable instrument, the Appraisal of Guidelines in Research and Evaluation II. Six domains were considered: 1) score and purpose; 2) stakeholder involvement; 3) rigor of development; 4) clarity of presentation; 5) applicability; and 6) editorial independence. The domains consist of a total of 23 items each scored on a 7-point scale. High quality CPGs were identified if they had a domain score above 60% in rigor of development, and two other domains. RESULTS: Of the three included CPGs, the Royal Australian College of General Practitioners (RACGP) and American College of Rheumatology (ACR) CPGs were considered to be of high quality, but the German Society for Pediatric Rheumatology was of lower quality. Domains one to four had high domain scores across the guidelines (mean (standard deviation)): 72.76 (13.80); 66.67 (9.81); 64.67 (7.77); and 87.00 (9.64), respectively. Lower scores were obtained for applicability (14.00 (5.57)) and editorial independence (43.44 (7.02)). Recommendations varied across CPGs due to differences in context, target audience (general practitioners, rheumatologists, and other multidisciplinary healthcare professionals) and patients' disease presentations. Despite this variability, progression of pharmacological treatment did not conflict between CPGs. Recommendations for non-pharmacological interventions were vague and the interventions considered varied between CPGs. CONCLUSIONS: Overall, recommendations were based on a paucity of evidence and weak study designs. Further research is needed on interventions in JIA, as well as higher quality CPGs to facilitate implementation of the best evidence-based recommendations in clinical practice. PMID- 26356099 TI - Health Facility Utilisation Changes during the Introduction of Community Case Management of Malaria in South Western Uganda: An Interrupted Time Series Approach. AB - BACKGROUND: Malaria endemic countries have scaled-up community health worker (CHW) interventions, to diagnose and treat malaria in communities with limited access to public health systems. The evaluations of these programmes have centred on CHW's compliance to guidelines, but the broader changes at public health centres including utilisation and diagnoses made, has received limited attention. METHODS: This analysis was conducted during a CHW-intervention for malaria in Rukungiri District, Western Uganda. Outpatient department (OPD) visit data were collected for children under-5 attending three health centres one year before the CHW-intervention started (pre-intervention period) and for 20 months during the intervention (intervention-period). An interrupted time series analysis with segmented regression models was used to compare the trends in malaria, non malaria and overall OPD visits during the pre-intervention and intervention period. RESULTS: The introduction of a CHW-intervention suggested the frequency of diagnoses of diarrhoeal diseases, pneumonia and helminths increased, whilst the frequency of malaria diagnoses declined at health centres. In May 2010 when the intervention began, overall health centre utilisation decreased by 63% compared to the pre-intervention period and the health centres saw 32 fewer overall visits per month compared to the pre-intervention period (p<0.001). Malaria visits also declined shortly after the intervention began and there were 27 fewer visits per month during the intervention-period compared with the pre intervention period (p<0.05). The declines in overall and malaria visits were sustained for the entire intervention-period. In contrast, there were no observable changes in trends of non-malarial visits between the pre-intervention and intervention-period. CONCLUSIONS: This analysis suggests introducing a CHW intervention can reduce the number of child malaria visits and change the profile of cases presenting at health centres. The reduction in workload of health workers may allow them to spend more time with patients or undertake additional curative or preventative roles. PMID- 26356100 TI - Are fibromyalgia and failed back surgery syndromes actually "functional somatic syndromes" in terms of their symptomatological, familial and psychological characteristics? A comparative study with chronic medical illness and healthy controls. AB - OBJECTIVES: The aim of this study was to investigate whether Fibromyalgia and Failed Back Surgery Syndromes (FMS-FBSS) may be evaluated under the single heading of Functional Somatic Syndromes (FSS) with respect to their symptomatological characteristics such as intensity, frequency, age of onset, duration, painful areas, fear of pain, and pain coping styles; familial characteristics such as family history of chronic medical illness, psychopathology and pain; and psychological characteristics such as manner of dealing with pain, fear of pain, alexithymia, symptom interpretation, somatosensory amplification and depression. METHODS: The study comprised 150 individuals, separated into 3 groups; The FSS Group comprised 47 patients who were referred to the Physical Medicine and Rehabilitation Clinic at Istanbul University's Faculty of Medicine with FMS (n=35) and FBSS (n=12), the healthy control group (HC Group) comprised 47 individuals, and the chronic medical illness control group (CMIC Group) was made up of 56 individuals. Turkish versions of the Toronto Alexithymia Scale, Symptom Attribution Inventory, Somatosensory Amplification Scale and Beck Depression Inventory, along with a semi-structured form questioning general health, pain and demographics were administered to all participants. RESULTS: FMS and FBSS participants (FSS Group) did not differ as a function of the major familial, symptomatological and clinical features considered in this study. Additionally, this group significantly differed from the HC and CMIC Groups with respect to almost all these features. CONCLUSION: This study is Important Insofar as it simultaneously evaluated FMS and FBSS groups in the presence of a control group. The results suggest that FMS and FBSS, currently treated as two different diagnostic categories in general medical practice, may be evaluated under the single heading of FSS. PMID- 26356101 TI - Perceptions of pain levels among orthopedic surgery patients, their relatives, and nurses. AB - OBJECTIVES: This descriptive study investigated pain levels of orthopedic surgery patients, and how this pain is perceived by their relatives and nurses. METHODS: The study was carried out with 150 patients, 150 relatives and 50 nurses to determine pain intensity levels of orthopedic surgery patients and perceptions of this among their relatives and nurses. Intensity of pain was measured on a 0 to 10 visual analogue scale. Relatives and nurses were not allowed to see the patient's pain intensity score, and each nurse was allowed to participate in pain measurement three times. The data were analyzed by descriptive statistics, the Mann Whitney-U test, Paired Sample t-Test, Linear Regression and Spearman Correlation Analysis. RESULTS: The pain intensity scores given by nurses (t=9.136, p<0.001) were significantly lower than patients' own scores. There was no significant difference between relatives' and patients' pain scores. In the regression analysis, pain intensity scores given by relatives were approximately 40% lower than those given by patients, while nurses' scores were approximately 60% lower. CONCLUSION: Education on pain management and the physical and emotional reactions of patients to pain should be provided for nurses working in surgical clinics. Meanwhile, as those who spend most time with the patient, relatives should be informed about possible pain behaviors in the postoperative period in order to prepare them for their role in the patient's care. PMID- 26356102 TI - [Our ultrasound-guided paravertebral block experiences in thoracic surgery]. AB - OBJECTIVES: Ultrasound-guided thoracic paravertebral block (TPVB) may be employed for postoperative analgesia in thoracic surgery. In application of TPVB, single injections, multiple injections or catheter techniques may be used. In this paper we present our experiences with ultrasound-guided TPVB in thoracic surgery patients for postoperative analgesia. METHODS: Patients undergoing thoracic surgery and on whom ultrasound-guided TPVB was performed for postoperative analgesia from January 2012 to March 2013 in our clinic were analyzed retrospectively. Demographic data, block technique, complications and 1st, 6th, 12th and 24th hour VAS scores were recorded. RESULTS: A total of 18 patients had TPVB. Single injection was administered to 9 patients, multiple injections to 5, and catheters to 4. While statistically insignificant, 1st hour VAS scores were found to be greater than 3 in the single injection and catheter groups. CONCLUSION: Similarly to multiple injection and continuous TPVB administration, ultrasound-guided single injection TPVB provides effective 24-hour postoperative analgesia. PMID- 26356103 TI - [An evaluation of the psychosocial characteristics of patients admitted to a pain clinic and their relatives]. AB - OBJECTIVES: This study tested the hypothesis that as pain brings about psychosocial changes in the pain patient, it also does in those relatives dealing with and supporting the patient. In order to test the hypothesis, comparisons of psychosocial status were made among patients with chronic pain, their relatives, and a control group (individuals having no pain and no relative with a pain disorder). METHODS: The study included 270 individuals separated into 3 groups: Patients admitted to the Pain Polyclinic at Dokuz Eylul University Faculty of Medicine with chronic pain (Group CP; n=77), relatives of these patients (Group R; n=98), and individuals age- and sex-matched to the relatives as a control group (Group C; n=95). The demographic values of all individuals were recorded, and psychological evaluations performed on all participants using the SCL 90 test. RESULTS: Somatization, anxiety, depression, interindividual sensibility, psychosis, paranoia, anger and general symptom index average scores were found to be high in Group R compared to Group C. CONCLUSION: Changes in psychosocial status were observed in pain patients and their relatives when compared to the control group. The study recommends that in addition to evaluating the psychological status of pain patients in order to provide them with psychological and medical support, relatives of these patients should also be evaluated carefully and given psychological and medical support to enable necessary diagnosis and treatment. PMID- 26356104 TI - [The prevalence of low back pain in hospital staff and its relationship with chronic fatigue syndrome and occupational factors]. AB - OBJECTIVES: This study aimed to investigate the occurrence of low back pain in hospital employees during the previous year and its correlation with demographic data, occupational factors and chronic fatigue syndrome. METHODS: All participants provided information on their socio-demographic background, occupational characteristics, their experience of low back pain during the previous year, and chronic fatigue syndrome. RESULTS: The study included 365 volunteers (221 male and 144 female). The mean age was 33.1 +/- 7.2. Of the 365 participants, 218 (59.7%) had experienced low back pain in the last year. No statistically significant difference was detected in age, height, weight, level of education, smoking habits, occupation, professional working hours, shift work or levels of income between the groups with and without low back pain. Low back pain was more frequent (p<0.05) in male workers. Chronic fatigue syndrome was statistically significant in the group suffering from low back pain (p<0.05), of whom 21.5% had chronic fatigue syndrome. We detected a statistically significant relationship (p<0.05) between chronic fatigue syndrome, occupational duration and shift work. CONCLUSION: To the best of our knowledge, this is the first to show the relationship between low back pain and chronic fatigue syndrome in hospital employees. Shift work and length of time in occupation are risk factors for chronic fatigue syndrome. PMID- 26356105 TI - [Postoperative analgesic effect of acupuncture in laparoscopic cholecystectomy surgery]. AB - OBJECTIVES: In surgery clinics, postoperative pain is a common occurrence and care is needed in its treatment. One form of treatment is various acupuncture techniques. This study investigated the effect of acupuncture on postoperative analgesia in patients undergoing laparoscopic cholecystectomy. METHODS: A total of 59 patients undergoing laparoscopic cholecystectomy were included in the study; 31 comprised the acupuncture group (Group A), and 29 constituted the control group (group C). All patients underwent standard anesthesia procedures. Patient-controlled analgesia with tramadol was administered postoperatively. Patients' postoperative pain scores, results of the satisfaction questionnaire and amounts of tramadol used were recorded. Postoperative 0, 1st, 2nd, 6th, 12th and 18th hour controls were performed. RESULTS: A comparison of the groups showed Group A pain scores to be significantly lower statistically than those of Group C at all postoperative controls. There was no statistically significant difference for postoperative analgesic consumption and satisfaction level between the groups. CONCLUSION: Despite detection of a reduction in postoperative pain scores, the application of acupuncture did not cause any change in the consumption of tramadol. PMID- 26356106 TI - Spontaneous intracranial hypotension presenting with coma: a case report and literature review. AB - Spontaneous intracranial hypotension is characterized by orthostatic headache in the absence of a history of head trauma or lumbar puncture, and diagnosis is confirmed by a specific cerebrospinal fluid pressure and neuroimaging findings. It rarely presents with coma. A 62-year-old man presented with progressive cognitive decline of 2 to 4 weeks' duration. He was diagnosed with spontaneous intracranial hypotension according to cerebrospinal fluid pressure and neuroimaging findings, and treated conservatively. PMID- 26356107 TI - Is back pain a diagnostic problem in clinical practices? A rare case report. AB - Multiple thoracic disc herniations are rare, and few reports exist in the literature. Diagnosis of these herniations is often missed because of their lack of specific clinical presentation. They may be treated conservatively or surgically. We presented a 35-year-old woman with five contiguous level thoracic disc herniations. She was admitted with upper back pain. Magnetic resonance imaging showed disc herniations at levels T6-7, T7-8, T8-9, T9-10 and T10-11. All were left sided and on the same line in the sagittal plane. The patient underwent conservative treatment. This report presented an unusual case and discussed its mechanisms. PMID- 26356108 TI - [Intrathecal bupivacaine and allergic reaction]. AB - By inhibiting sodium channels, local anesthetics (LAs) prevent sodium entering the cell and inhibit cellular depolarization. Although undesired drug reactions caused by LA usage are common, real allergic reactions are rare. The objective of this study was to discuss allergic reactions developing after application of spinal anesthetic. PMID- 26356109 TI - An exceptional indication for bilateral thoracic paravertebral block performance in a pediatric patient. PMID- 26356110 TI - Combined thermo-chemo-sonic disintegration of waste activated sludge for biogas production. AB - In the present study, there was an investigation about the impact of a new combined thermo-chemo-sonic disintegration of waste activated sludge (WAS) on biodegradability. The outcome of sludge disintegration reveals that maximum Suspended Solids (SS) reduction and Chemical Oxygen Demand (COD) solubilization effectuated at a specific energy input of 5290.5kJ/kgTS, and was found to be 20%, 16.4%, 15% and 27%, 22%, and 20%, respectively for the three alkalis (NaOH, KOH, and Ca(OH)2). The conversion coefficient of the Volatile Suspended Solids (VSS) to product Soluble COD (SCOD), calculated by nonlinear regression modeling, was found to be 0.5530gSCOD/gVSS, 0.4587gSCOD/gVSS, and 0.4195gSCOD/gVSS for NaOH, KOH, and Ca(OH)2, respectively. In the biodegradability studies, the parameter evaluation provides an estimate of parameter uncertainty and correlation, and elucidates that there is no significant difference in biodegradability (0.413gCOD/gCOD, 0.367gCOD/gCOD, and 0.342gCOD/gCOD) for three alkalis (NaOH, KOH, and Ca(OH)2). PMID- 26356111 TI - Efficient alachlor degradation by the filamentous fungus Paecilomyces marquandii with simultaneous oxidative stress reduction. AB - The acceleration of alachlor degradation by Paecilomyces marquandii under controlled and optimized conditions of fungal cultivation in liquid batches was observed (by ca. 20% in comparison to the flask cultures). Acidic environment and oxygen limitation resulted in deterioration of herbicide elimination. Efficient xenobiotic degradation did not correlate with free radicals formation, but some conditions of bioreactor cultivation such as neutral pH and oxygen enriched atmosphere (pO2?30%) caused a decrease in the reactive oxygen species (ROS) accumulation in mycelia. The changes in the glutathione (GSH) and ascorbic acid (AA) levels, also in the dismutase (SOD) and catalase (CAT) activities showed active response of the tested fungus against alachlor induced oxidative stress. These results will contribute to the improvement of chloroacetanilides elimination by fungi and extend the knowledge concerning oxidative stress induction and fungal cellular defense. PMID- 26356112 TI - Endogenously enhanced biosurfactant production promotes electricity generation from microbial fuel cells. AB - Microbial fuel cell (MFC) is considered as a promising green energy source and energy-saving pollutants treatment technology as it integrates pollutant biodegradation with energy extraction. In this work, a facile approach to enhance endogenous biosurfactant production was developed to improve the electron transfer rate and power output of MFC. By overexpression of rhlA, the key gene responsible for rhamnolipids synthesis, over-production of self-synthesized rhamnolipids from Pseudomonas aeruginosa PAO1 was achieved. Strikingly, the increased rhamnolipids production by rhlA overexpression significantly promoted the extracellular electron transfer of P. aeruginosa by enhancing electron shuttle (pyocyanin) production and increasing bacteria attachment on the anode. As a result, the strain with endogenously enhanced rhamnolipids production delivered 2.5 times higher power density output than that of the parent strain. This work substantiated that the enhancement on endogenous biosurfactant production could be a promising approach for improvement on the electricity output of MFC. PMID- 26356113 TI - Enhanced biohydrogen production from sugarcane bagasse by Clostridium thermocellum supplemented with CaCO3. AB - Clostridium thermocellum ATCC 27405 was used to degrade sugarcane bagasse (SCB) directly for hydrogen production, which was significantly enhanced by supplementing medium with CaCO3. The effect of CaCO3 concentration on the hydrogen production was investigated. The hydrogen production was significantly enhanced with the CaCO3 concentration increased from 10mM to 20mM. However, with the CaCO3 concentration further increased from 20mM to 100mM, the hydrogen production didn't increase further. Under the optimal CaCO3 concentration of 20mM, the hydrogen production reached 97.83+/-5.19mmol/L from 2% sodium hydroxide pretreated SCB, a 116.72% increase over the control (45.14+/-1.03mmol/L), and the yield of hydrogen production reached 4.89mmol H2/g SCBadded. Additionally, CaCO3 promoted the biodegradation of SCB and the growth of C. thermocellum. The stimulatory effects of CaCO3 on biohydrogen production are mainly attributed to the buffering capacity of carbonate. The study provides a novel strategy to enhance biohydrogen production from lignocellulose. PMID- 26356114 TI - Effects of membrane orientation on fouling characteristics of forward osmosis membrane in concentration of microalgae culture. AB - Application of forward osmosis (FO) membrane to microalgae cultivation processes enables concentration of microalgae and nutrients with low energy consumption. To understand fouling characteristics of FO membrane in concentration of microalgae culture, we studied flux decline, flux recovery by cleaning, and foulants characteristics, in different membrane orientation of active-layer-facing-feed solution (AL-FS) and active-layer-facing-draw-solution (AL-DS) modes. Batch concentration of Chlorella vulgaris was conducted with a cellulose-triacetate FO membrane. Rapid flux decline and lower flux recovery was observed in AL-DS mode because of inner-membrane fouling including internal pore clogging, adsorption and internal concentration polarization in the support layer. A proportion of polysaccharides in extracellular polymeric substances to soluble microbial products were larger in chemical cleaning effluent than physical one in AL-DS mode, although those were not significantly different in AL-FS mode. Excitation emission matrix analysis revealed that proteins and humic-like substances were also possible irreversible foulants both in AL-DS and AL-FS modes. PMID- 26356115 TI - Development of a modified independent parallel reactions kinetic model and comparison with the distributed activation energy model for the pyrolysis of a wide variety of biomass fuels. AB - The pyrolysis of six waste biomass samples was studied and the fuels were kinetically evaluated. A modified independent parallel reactions scheme (IPR) and a distributed activation energy model (DAEM) were developed and their validity was assessed and compared by checking their accuracy of fitting the experimental results, as well as their prediction capability in different experimental conditions. The pyrolysis experiments were carried out in a thermogravimetric analyzer and a fitting procedure, based on least squares minimization, was performed simultaneously at different experimental conditions. A modification of the IPR model, considering dependence of the pre-exponential factor on heating rate, was proved to give better fit results for the same number of tuned kinetic parameters, comparing to the known IPR model and very good prediction results for stepwise experiments. Fit of calculated data to the experimental ones using the developed DAEM model was also proved to be very good. PMID- 26356116 TI - Utilization of agro-wastes to inhibit aflatoxins synthesis by Aspergillus parasiticus: A biotreatment of three cereals for safe long-term storage. AB - The growth of Aspergillus parasiticus and aflatoxins production were inhibited during storage of three important cereals (wheat, maize and rice) using leaves of neem (Azadirachta indica) and kikar (Acacia nilotica). Cereals were inoculated with mould spores and stabilized by neem and kikar leaves-powder. Test samples with moisture levels of 21% were stored at 30 degrees C for a period of 9months. Aflatoxins were quantified at different time intervals in stored cereals. Neem leaves fully inhibited all types of aflatoxins synthesis for 4months in wheat and for 2months in maize while in rice inhibited synthesis of only B2, G1 and G2 aflatoxin for 3months. Kikar leaves fully inhibited aflatoxin B2, G1 and G2 for 3months in wheat, and for 2months in maize. Among two investigated plants, neem leaves were found more effective for preventing the production of all types of aflatoxins in cereals' long-term storage. PMID- 26356117 TI - Debottlenecking product inhibition in 1,3-propanediol fermentation by In-Situ Product Recovery. AB - The present work describes the application of liquid-liquid extraction as an In Situ product recovery (ISPR) technique to overcome the problem of product inhibition in 1,3-PD fermentation. As a part of initial screening experiments, six solvents were subjected to phase separation and biocompatibility tests to find the best extractant for in-situ removal of 1,3-PD from the bioreactor. These included tributylphosphate, ethyl acetate, butyl acetate, oleyl alcohol, oleic acid and hexanol. Of these, ethyl acetate was found to be the most suitable solvent for 1,3-PD extraction. Use of the selected extractant in continuous integrated fermentation-extraction was established by batch and fed-batch extractive fermentations which demonstrated a significantly improved 1,3-PD production of 35g/L and 74.5g/L, respectively. A steady state 1,3-PD concentration of 58g/L was obtained in continuous extractive system. Continuous cultivation with in-situ cell retention and in-situ 1,3-PD removal demonstrated a 5-fold enhancement in 1,3-PD productivity over non-extractive batch. PMID- 26356118 TI - Effects of various amino acids as organic nitrogen sources on the growth and biochemical composition of Chlorella pyrenoidosa. AB - This study investigated the effects of eighteen l-amino acids on the growth and biochemical composition of Chlorella pyrenoidosa. Under the nitrate deficiency condition, ten l-amino acids were found to exert stronger stimulative effects on the algal growth than the other amino acids. After 10-day culture, addition of 0.5gL(-1) the above mentioned ten amino acids significantly increased the cellular protein contents by 441.3-110.8%, respectively, and significantly decreased the carbohydrate contents by 60.7-16.2%, respectively. Under the normal nitrate condition, the cellular biochemical composition was not significantly affected by addition of serine, leucine, proline, aspartic acid, asparagine, and glycine, whereas addition of aspartic acid and arginine increased the algal biomass by 110.2% and 62.8% compared with the control. Finally, the significance of this work in the biotechnological application of culturing C. pyrenoidosa in organic wastewater rich in amino acids was further discussed. PMID- 26356119 TI - Enhanced removal of naproxen and carbamazepine from wastewater using a novel countercurrent seepage bioreactor immobilized with Phanerochaete chrysosporium under non-sterile conditions. AB - A countercurrent seepage bioreactor immobilized with Phanerochaete chrysosporium was continuously operated under non-sterile conditions to treat a synthetic wastewater spiked with naproxen and carbamazepine (1000MUg/L each) for 165days. There were no serious bacterial contaminations occurred during the operational period. Naproxen was always removed to the undetectable level regardless of the experimental conditions, while the average removal efficiency for carbamazepine, a well-known recalcitrant pharmaceutically active compound, reached around 80%. The excellent removal performance was mainly attributed to the application of countercurrent seepage mode and the cardhouse fabric of the carriers, which provided the high efficiency in the transfer of oxygen and nutrients inside the bioreactor. From the fungal immobilization combined with the temperature adjustment, the fungal activity including the enzyme production was protected as well as the bacterial contamination inside the reactor was suppressed effectively. PMID- 26356121 TI - A Combined Experimental and Computational Study of an Aluminum Triflate/Diglyme Electrolyte. AB - The physicochemical properties of aluminum trifluoromethanesulfonate in diglyme have been investigated. The spectroscopic and electrochemical properties have been examined to determine speciation, conductivity, and electrochemical stability. Gaussian calculations provide optimized molecular geometries and offer insight into the electrochemical behavior of the solutions. The ions in solution appear to exhibit very straightforward behavior, with contact ion pairs forming at very low concentrations. In addition, the electrochemical window of the electrolyte initially decreases with increasing salt concentration to a minimum value of approximately 5.5 V around 1 M and then steadily rises to a maximum value above 8 V. PMID- 26356120 TI - Electrochemotherapy of colorectal liver metastases--an observational study of its effects on the electrocardiogram. AB - BACKGROUND: Electrochemotherapy (ECT) is a combined treatment in which high voltage electroporation (EP) pulses are used to facilitate the uptake of a chemotherapeutic drug into tumor cells, thus increasing antitumor effectiveness of the drug. The effect of ECT of deep-seated tumors located close to the heart on functioning of the heart has not been previously investigated. In this study, we investigate the effects of intra-abdominal ECT of colorectal liver metastases on functioning of the heart during the early post-operative care period. METHODS: For ECT high voltage EP pulses with amplitudes of up to 3000 V and 30 A were delivered in synchronization with electrical activity of the heart. Holter electrocardiographic (ECG) signals were obtained from 10 patients with colorectal liver metastases treated with ECT. ECG was recorded during the periods of 24 hours before and after the surgical procedure involving ECT. Four-hour long night time ECG segments from both periods exhibiting the highest level of signal stationarity were analyzed and compared. Changes in several ECG and heart rate variability (HRV) parameters were evaluated. RESULTS: No major heart rhythm changes (i.e., induction of extrasystoles, ventricular tachycardia or fibrillation) or pathological morphological changes (i.e., ST segment changes) indicating myocardial ischemia were found. However, we found several minor statistically significant but clinically irrelevant changes in HRV parameters after ECT procedures: a decrease in median values of the mean NN interval, a decrease in the low-frequency and in the normalized low-frequency component, and an increase in the normalized high-frequency component. CONCLUSIONS: Only minor effects of intra-abdominal ECT treatment on functioning of the heart were found. They were expressed as statistically significant but clinically irrelevant changes in heart rate and long-term HRV parameters and were as such not life threatening to the patients. The nature of these changes is such that they can be attributed to the known effects of the drugs given to the patients in the post operative care. Further investigation is still warranted to unambiguously resolve whether ECT with high voltage EP pulses applied in immediate vicinity of the heart is responsible for the observed effects. PMID- 26356122 TI - Expression of IL-17A, E, and F and their receptors in human prostatic cancer: Comparison with benign prostatic hyperplasia. AB - BACKGROUND: Benign prostatic hyperplasia (BPH) and prostate cancer (PCa) are the most common urological diseases in elderly men. Although studies suggest the cytokine family might be associated with BPH and PCa, there has been no systematic comparisons of expression of IL-17A, E, F and their receptors, infiltration of inflammatory cells, and changes in structural cells in PCa and BPH. METHODS: Immunohistochemistry was employed to evaluate immunoreactivity for IL-17A, E, F and their receptors IL-17RA, IL-17BR, and IL-17CR, infiltration of inflammatory cells, and changes in structural cells including endothelial cells, fibroblasts, and smooth muscle cells in prostate tissues from subjects with PCa or BPH as well as controls. RESULTS: Immunostaining showed that expression of immunoreactivity for IL-17A, IL-17RA, IL-17E, and IL-17F was significantly elevated in prostatic tissue from BPH and PCa compared with that in controls, which was accompanied by increased numbers of infiltrating inflammatory cells and CD31(+) blood vessels. Compared with BPH, PCa was characterized by reduced immunoreactivity for IL-17BR and reduced numbers of CD68(+) macrophages, fibroblasts, and smooth muscle cells, although there was a trend for these changes to correlate with disease severity in both PCa and BPH. CONCLUSION: Our data are compatible with hypothesis that IL-17A acting through IL-17RA, but not IL-17CR contribute to the pathogenesis of BPH and PCa. In contrast, IL-17E interacting with the IL-17BR might have an anti-tumor effect. PMID- 26356123 TI - Blind colour separation of H&E stained histological images by linearly transforming the colour space. AB - Blind source separation methods aim to split information into the original sources. In histology, each dye component attempts to specifically characterize different microscopic structures. In the case of the hematoxylin-eosin stain, universally used for routine examination, quantitative analysis may often require the inspection of different morphological signatures related mainly to nuclei patterns, but also to stroma distribution. Stain separation is usually a preprocessing operation that is transversal to different applications. This paper presents a novel colour separation method that finds the hematoxylin and eosin clusters by projecting the whole (r,g,b) space to a folded surface connecting the distributions of a series of [(r-b),g] planes that divide the cloud of H&E tones. The proposed method produces density maps closer to those obtained with the colour mixing matrices set by an expert, when comparing with the density maps obtained using nonnegative matrix factorization (NMF), independent component analysis (ICA) and a state-of-the-art method. The method has outperformed three baseline methods, NMF, Macenko and ICA, in about 8%, 12% and 52% for the eosin component, whereas this was about 4%, 8% and 26% for the hematoxylin component. PMID- 26356130 TI - Patterns and Predictors of Sensorineural Hearing Loss in Children With Congenital Diaphragmatic Hernia. AB - Importance: Although congenital diaphragmatic hernia (CDH) may be associated with sensorineural hearing loss (SNHL), to our knowledge, no studies have yet identified the pattern of this hearing loss or definitive independent risk factors that may place this population at higher risk. Objective: To characterize the type and degree or SNHL in CDH survivors and better characterize perinatal risk factors. Design, Setting, and Participants: This was a retrospective cohort study of CDH survivors who had a pure-tone audiogram available for review followed at a multidisciplinary clinic. Interventions: Treatment for CDH at birth. Main Outcomes and Measures: Audiograms were used to calculate pure-tone average (PTA) for the most severely affected side and classify SNHL as normal (<20 dB), mild (20-39 dB), moderate (>40-59 dB), severe (>=60 dB), or profound (>=80 dB). Clinically significant SNHL was defined as a PTA of at least 40 dB. Perinatal data evaluated included demographics, characteristics of CDH and neonatal respiratory course, peak total and direct bilirubin levels, exposure to ototoxic drugs, need for supplemental oxygen at discharge, and results of newborn hearing screen. Univariate analysis was conducted to examine the relationship between these variables and (1) any SNHL or (2) significant SNHL. Results: Fifty patients were included. Audiograms were performed at age 2.7 +/- 2.3 years (range, 0.5-10.7 years). Of the 50 patients, 28 (56%) had any SNHL and 9 of the 28 (32%) had significant SNHL (PTA >= 40 dB). Any SNHL was not significantly different (P = .42) by newborn hearing screen results: 5 of 7 children (71%) who failed the screening were classified as having any SNHL, and 20 of 40 children (50%) who passed were classified as having any SNHL. While no variables were significantly associated with any SNHL, multiple significant associations were found with significant SNHL: extracorporeal membrane oxygenation support (P = .02), nonprimary CDH repair (P = .01), prolonged ventilation (>=14 days) (P = .001), and high neonatal furosemide exposure (P = .03). Conclusions and Relevance: Sensorineural hearing loss is prevalent among children with CDH. As would be expected, significant SNHL (PTA >= 40 dB) in this cohort was associated with markers of more severe CDH with a more complicated neonatal hospital course. Overall close follow-up for hearing and speech development, including routine audiology testing, is indicated in children with CDH. PMID- 26356124 TI - Autoimmune Hepatitis: Clinical Review with Insights into the Purinergic Mechanism of Disease. AB - Autoimmune hepatitis (AIH) is an important disorder that predominantly results in inflammatory liver disease in genetically predisposed women. The clinicopathological picture is characterized by symptoms associated with both systemic inflammation and hepatic dysfunction, and with increased serum aminotransferases, elevated IgG, autoantibodies, and interface hepatitis on liver biopsy. AIH usually results in liver injury as a consequence of chronic hepatitis and cirrhosis. However, rarely, patients may present with fulminant liver failure. Early diagnosis is important in all instances because the disease can be highly responsive to immunosuppressive therapeutic options. Left untreated, the disease is associated with high morbidity and mortality. Here we provide an overview of the current state of knowledge on AIH and summarize the treatment options for this serious condition in adults. We also discuss the pathogenesis of the disease as a possible consequence of autoimmunity and the breakdown of hepatic tolerance. We focus on regulatory T cell impairments as a consequence of changes in CD39 ectonucleotidase expression and altered purinergic signaling. Further understanding of hepatic tolerance may aid in the development of specific and well-tolerated therapies for AIH. PMID- 26356131 TI - Function-Led Design of Aerogels: Self-Assembly of Alloyed PdNi Hollow Nanospheres for Efficient Electrocatalysis. AB - One plausible approach to endow aerogels with specific properties while preserving their other attributes is to fine-tune the building blocks. However, the preparation of metallic aerogels with designated properties, for example catalytically beneficial morphologies and transition-metal doping, still remains a challenge. Here, we report on the first aerogel electrocatalyst composed entirely of alloyed PdNi hollow nanospheres (HNSs) with controllable chemical composition and shell thickness. The combination of transition-metal doping, hollow building blocks, and the three-dimensional network structure make the PdNi HNS aerogels promising electrocatalysts for ethanol oxidation. The mass activity of the Pd83 Ni17 HNS aerogel is 5.6-fold higher than that of the commercial Pd/C catalyst. This work expands the exploitation of the electrocatalysis properties of aerogels through the morphology and composition control of its building blocks. PMID- 26356132 TI - Why follow-back studies should be interpreted cautiously: The case of an HPV negative cervical lesion. PMID- 26356133 TI - The state of midline closure of the abdominal wall. PMID- 26356134 TI - Brain Imaging for Staging of Patients With Clinical Stage IA Non-small Cell Lung Cancer in the National Lung Screening Trial: Adherence With Recommendations From the Choosing Wisely Campaign. AB - BACKGROUND: The Choosing Wisely recommendations from the Society of Thoracic Surgeons include avoiding brain imaging in asymptomatic patients with early-stage non-small cell lung cancer (NSCLC). We aimed to describe use of brain imaging among National Lung Screening Trial participants with stage IA NSCLC and to identify factors associated with receipt of brain imaging. METHODS: We identified patients with clinical stage IA NSCLC who received CT scans or magnetic resonance brain imaging within 60 days after diagnosis, but before definitive surgical staging. Using multivariate logistic regression, we identified variables associated with undergoing brain imaging. RESULTS: Among 643 patients with clinical stage IA NSCLC, 77 patients (12%) received at least one brain imaging study. Of seven patients (1.1%) who were upstaged to stage IV, only two underwent brain imaging and neither had documentation of brain metastasis. Brain imaging frequency by enrollment center varied from 0% to 80%. All patients who underwent brain imaging subsequently underwent surgery with curative intent, suggesting strongly that imaging revealed no evidence of intracranial metastases. In multivariate analyses, primary tumor size >20 mm (OR, 2.50; 95% CI, 1.50-4.16; P < .001) and age 65 to 69 (OR, 2.78; 95% CI, 1.38-5.57; P < .01) were independently associated with greater use of brain imaging. CONCLUSIONS: Among National Lung Screening Trial patients with stage IA NSCLC, one in eight underwent brain imaging, but none ultimately had intracranial metastases. Larger tumor size and older age were associated with greater use of brain imaging. Wide variation in use between centers suggests either lack of awareness or disagreement about this Choosing Wisely recommendation. PMID- 26356135 TI - Minimal genome: Worthwhile or worthless efforts toward being smaller? AB - Microbial cells are versatile hosts for the production of value-added products due to the well-established background knowledge, various genetic tools, and ease of manipulation. Despite those advantages, efficiency of newly incorporated synthetic pathways in microbial cells is frequently limited by innate metabolism, product toxicity, and growth-mediated genetic instability. To overcome those obstacles, a minimal genome harboring only the essential set of genes was proposed, which is a fascinating concept with potential for use as a platform strain. Here, we review the currently available artificial reduced genomes and discuss the prospects for extending use of the genome-reduced strains as programmable chasses. The genome-reduced strains generally showed comparable growth to and higher productivity than their ancestral strains. In Escherichia coli, about 300 genes are estimated as the minimal number of genes under laboratory conditions. However, recent advances revealed that there are non essential components in essential genes, suggesting that the design principle of minimal genomes should be reconstructed. Current technology is not efficient enough to reduce large amount of interspaced genomic regions or to synthesize the genome. Furthermore, construction of minimal genome frequently has failed due to lack of genomic information. Technological breakthroughs and intense systematic studies on genomes remain tasks. PMID- 26356136 TI - Synthesis and structural identification of fluorine-18 labeled parathyroid hormone. AB - Parathyroid hormone (PTH) is an 84 amino acid peptide hormone that plays a key role in bone and mineral metabolism. The biological actions of PTH are mediated via the N-terminal PTH(1-34) fragment, serving as the PTH receptor-binding sequence, and which is therefore used clinically to treat conditions of low bone mass such as osteoporosis. In this study, PTH(1-34) was conjugated with non radioactive (stable F isotope) N-succinimidyl 4-fluorobenzoate (SFB) leading to three isomeric mono-fluorobenzoated (FBz) PTH followed by Liquid chromatography Tandem mass spectrometry (LC-MS/MS) assisted structural identification. Corresponding [(18)F]SFB-labeled PTH derivatives were prepared respectively and the Lys(13) site-specific labeled [(18)F]FBz PTH was isolated by HPLC with radiochemical purity >99% and specific activity of 2.78 GBq/umol, suitable for future application with in vivo pharmacokinetic/pharmacodynamic studies of PTH, using preclinical Positron Emission Tomography Computed Tomography (PET/CT) imaging. PMID- 26356137 TI - Consecutive percutaneous valve-in-valve replacement late after Ross procedure: A novel approach in an adult with congenital heart disease. AB - The emergence of transcatheter valve technology over the last decade has made significant impact on the treatment of patients with valvular heart disease. There has been increasing experience with both native and valve-in-valve indications with promising results. We present the case of a young woman with congenital heart disease who underwent the Ross procedure for bicuspid aortic valve endocarditis with subsequent reoperation and surgical aortic valve replacement for neo-aortic root dilation who experienced worsening symptoms related to both pulmonary and aortic valve dysfunction. She was successfully treated with percutaneous pulmonary and aortic valve replacement with excellent early term technical results and marked improvement in symptoms. PMID- 26356138 TI - Psychiatric evaluations prior to stem cell transplant - a survey of National Marrow Donor Programs. PMID- 26356140 TI - Team-Based Models for End-of-Life Care: An Evidence-Based Analysis. AB - BACKGROUND: End of life refers to the period when people are living with advanced illness that will not stabilize and from which they will not recover and will eventually die. It is not limited to the period immediately before death. Multiple services are required to support people and their families during this time period. The model of care used to deliver these services can affect the quality of the care they receive. OBJECTIVES: Our objective was to determine whether an optimal team-based model of care exists for service delivery at end of life. In systematically reviewing such models, we considered their core components: team membership, services offered, modes of patient contact, and setting. DATA SOURCES: A literature search was performed on October 14, 2013, using Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid Embase, EBSCO Cumulative Index to Nursing & Allied Health Literature (CINAHL), and EBM Reviews, for studies published from January 1, 2000, to October 14, 2013. REVIEW METHODS: Abstracts were reviewed by a single reviewer and full-text articles were obtained that met the inclusion criteria. Studies were included if they evaluated a team model of care compared with usual care in an end-of-life adult population. A team was defined as having at least 2 health care disciplines represented. Studies were limited to English publications. A meta-analysis was completed to obtain pooled effect estimates where data permitted. The GRADE quality of the evidence was evaluated. RESULTS: Our literature search located 10 randomized controlled trials which, among them, evaluated the following 6 team based models of care: *hospital, direct contact *home, direct contact *home, indirect contact *comprehensive, indirect contact *comprehensive, direct contact *comprehensive, direct, and early contact Direct contact is when team members see the patient; indirect contact is when they advise another health care practitioner (e.g., a family doctor) who sees the patient. A "comprehensive" model is one that provides continuity of service across inpatient and outpatient settings, e.g., in hospital and then at home. All teams consisted of a nurse and physician at minimum, at least one of whom had a specialty in end-of-life health care. More than 50% of the teams offered services that included symptom management, psychosocial care, development of patient care plans, end-of-life care planning, and coordination of care. We found moderate-quality evidence that the use of a comprehensive direct contact model initiated up to 9 months before death improved informal caregiver satisfaction and the odds of having a home death, and decreased the odds of dying in a nursing home. We found moderate quality evidence that the use of a comprehensive, direct, and early (up to 24 months before death) contact model improved patient quality of life, symptom management, and patient satisfaction. We did not find that using a comprehensive team-based model had an impact on hospital admissions or length of stay. We found low-quality evidence that the use of a home team-based model increased the odds of having a home death. LIMITATIONS: Heterogeneity in data reporting across studies limited the ability to complete a meta-analysis on many of the outcome measures. Missing data was not managed well within the studies. CONCLUSIONS: Moderate-quality evidence shows that a comprehensive, direct-contact, team-based model of care provides the following benefits for end-of-life patients with an estimated survival of up to 9 months: it improves caregiver satisfaction and increases the odds of dying at home while decreasing the odds of dying in a nursing home. Moderate-quality evidence also shows that improvement in patient quality of life, symptom management, and patient satisfaction occur when end-of life care via this model is provided early (up to 24 months before death). However, using this model to deliver end-of-life care does not impact hospital admissions or hospital length of stay. Team membership includes at minimum a physician and nurse, with at least one having specialist training and/or experience in end-of-life care. Team services include symptom management, psychosocial care, development of patient care plans, end-of-life care planning, and coordination of care. PMID- 26356141 TI - Prevalence and association of hepatitis C virus infection with different types of lymphoma. PMID- 26356142 TI - Micheliolide overcomes KLF4-mediated cisplatin resistance in breast cancer cells by downregulating glutathione. AB - Micheliolide (MCL) is a promising novel compound with broad-spectrum anticancer activity. However, little is known regarding its action and mechanism in breast cancer. To explore the potential therapeutic application of MCL as a chemosensitivity modulator, this study investigated the effects of MCL on cisplatin sensitivity in breast cancer and the underlying mechanisms. In the 3 (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cytotoxicity assay and a xenograft tumor model, MCL enhanced the cisplatin sensitivity of the breast cancer cell line MCF-7 both in vitro and in vivo. Treatment of MCF-7 cells with low-dose cisplatin (10 uM) was sufficient to enrich the proportion of ALDH(+) cells and upregulate Kruppel-like factor 4 (KLF4) expression. The results obtained from knockdown and overexpression experiments demonstrate that KLF4 is both necessary and sufficient to induce a cisplatin resistance phenotype in breast cancer cells. Furthermore, the glutathione (GSH) content was elevated in MCF-7 cells after overexpression of KLF4. KLF4-mediated resistance to cisplatin was found to be abrogated by treatment with buthionine sulfoximine, an inhibitor of GSH synthesis. MCL induced GSH depletion and severe cell death in KLF4 overexpressing MCF-7 cells following exposure to cisplatin. Therefore, these results suggest that MCL-mediated direct depletion of GSH represents a major mechanism in reversing KLF4-induced cisplatin resistance in MCF-7 cells. PMID- 26356143 TI - Selection on bristle length has the ability to drive the evolution of male abdominal appendages in the sepsid fly Themira biloba. AB - Many exaggerated and novel traits are strongly influenced by sexual selection. Although sexual selection is a powerful evolutionary force, underlying genetic interactions can constrain evolutionary outcomes. The relative strength of selection vs. constraint has been a matter of debate for the evolution of male abdominal appendages in sepsid flies. These abdominal appendages are involved in courtship and mating, but their function has not been directly tested. We performed mate choice experiments to determine whether sexual selection acts on abdominal appendages in the sepsid Themira biloba. We tested whether appendage bristle length influenced successful insemination by surgically trimming the bristles. Females paired with males that had shortened bristles laid only unfertilized eggs, indicating that long bristles are necessary for successful insemination. We also tested whether the evolution of bristle length was constrained by phenotypic correlations with other traits. Analyses of phenotypic covariation indicated that bristle length was highly correlated with other abdominal appendage traits, but was not correlated with abdominal sternite size. Thus, abdominal appendages are not exaggerated traits like many sexual ornaments, but vary independently from body size. At the same time, strong correlations between bristle length and appendage length suggest that selection on bristle length is likely to result in a correlated increase in appendage length. Bristle length is under sexual selection in T. biloba and has the potential to evolve independently from abdomen size. PMID- 26356144 TI - Prediction of Dynamic Postural Stability During Single-Leg Jump Landings by Ankle and Knee Flexibility and Strength. AB - CONTEXT: Dynamic postural stability is important for injury prevention, but little is known about how lower-extremity musculoskeletal characteristics (range of motion [ROM] and strength) contribute to dynamic postural stability. Knowing which modifiable physical characteristics predict dynamic postural stability can help direct rehabilitation and injury-prevention programs. OBJECTIVE: To determine if trunk, hip, knee, and ankle flexibility and strength variables are significant predictors of dynamic postural stability during single-leg jump landings. DESIGN: Cross-sectional study. SETTING: Laboratory. PARTICIPANTS: 94 male soldiers (age 28.2 +/- 6.2 y, height 176.5 +/- 2.6 cm, weight 83.7 +/- 26.0 kg). INTERVENTION: None. MAIN OUTCOME MEASURES: Ankle-dorsiflexion and plantar flexion ROM were assessed with a goniometer. Trunk, hip, knee, and ankle strength were assessed with an isokinetic dynamometer or handheld dynamometer. The Dynamic Postural Stability Index (DPSI) was used to quantify postural stability. Simple linear and backward stepwise-regression analyses were used to identify which physical characteristic variables were significant predictors of DPSI. RESULTS: Simple linear-regression analysis revealed that individually, no variables were significant predictors of the DPSI. Stepwise backward-regression analysis revealed that ankle-dorsiflexion flexibility, ankle-inversion and -eversion strength, and knee-flexion and -extension strength were significant predictors of the DPSI (R2 = .19, P = .0016, adjusted R2 = .15). CONCLUSION: Ankle-dorsiflexion ROM, ankle-inversion and -eversion strength, and knee-flexion and -extension strength were identified as significant predictors of dynamic postural stability, explaining a small amount of the variance in the DPSI. PMID- 26356145 TI - A hexaphenylbenzene based AIEE active two photon probe for the detection of hydrogen sulfide with tunable self-assembly in aqueous media and application in live cell imaging. AB - Supramolecular aggregates of hexaphenylbenzene derivative exhibit aggregation induced emission enhancement and modulation of self-assembled architecture from spherical to flower-like assembly in the presence of H2S. Furthermore, probe displays higher photostability, low toxicity and bright green fluorescence in two photon microscopy (TPM) imaging for the detection of H2S in live HeLa cells. PMID- 26356146 TI - Development of professional identity during early training in oral and maxillofacial surgery: a qualitative study. AB - Development of professional identity is becoming increasingly important in medical education, and has been found to be beneficial in a surgeon's training. However, despite the complex, demanding nature of early training in oral and maxillofacial surgery (OMFS), we know of little research on how it develops during this time. We therefore used qualitative research methodology based on a grounded theory approach to investigate how trainees gain a sense of identity as they progress through their 2 undergraduate degrees. Data from in-depth, semi structured interviews with OMFS specialist trainees were transcribed and coded to allow for thematic analysis and subsequent theory construction. We propose a model of how professional identity develops in early OMFS training. Of note, professional experience gained during the second degree was found to be of great importance in the development of a strong professional identity. We look at reasons for this in terms of "cognitive space" and use the concept to discuss potential improvements to the training pathway. PMID- 26356147 TI - Scrunching: a novel escape gait in planarians. AB - The ability to escape a predator or other life-threatening situations is central to animal survival. Different species have evolved unique strategies under anatomical and environmental constraints. In this study, we describe a novel musculature-driven escape gait in planarians, 'scrunching', which is quantitatively different from other planarian gaits, such as gliding and peristalsis. We show that scrunching is a conserved gait among different flatworm species, underlying its importance as an escape mechanism. We further demonstrate that it can be induced by a variety of physical stimuli, including amputation, high temperature, electric shock and low pH. We discuss the functional basis for scrunching as the preferential gait when gliding is impaired due to a disruption of mucus production. Finally, we show that the key mechanical features of scrunching are adequately captured by a simple biomechanical model that is solely based on experimental data from traction force microscopy and tissue rheology without fit parameters. Together, our results form a complete description of this novel form of planarian locomotion. Because scrunching has distinct dynamics, this gait can serve as a robust behavioral readout for studies of motor neuron and muscular functions in planarians and in particular the restoration of these functions during regeneration. PMID- 26356148 TI - A simulation system for biomarker evolution in neurodegenerative disease. AB - We present a framework for simulating cross-sectional or longitudinal biomarker data sets from neurodegenerative disease cohorts that reflect the temporal evolution of the disease and population diversity. The simulation system provides a mechanism for evaluating the performance of data-driven models of disease progression, which bring together biomarker measurements from large cross sectional (or short term longitudinal) cohorts to recover the average population wide dynamics. We demonstrate the use of the simulation framework in two different ways. First, to evaluate the performance of the Event Based Model (EBM) for recovering biomarker abnormality orderings from cross-sectional datasets. Second, to evaluate the performance of a differential equation model (DEM) for recovering biomarker abnormality trajectories from short-term longitudinal datasets. Results highlight several important considerations when applying data driven models to sporadic disease datasets as well as key areas for future work. The system reveals several important insights into the behaviour of each model. For example, the EBM is robust to noise on the underlying biomarker trajectory parameters, under-sampling of the underlying disease time course and outliers who follow alternative event sequences. However, the EBM is sensitive to accurate estimation of the distribution of normal and abnormal biomarker measurements. In contrast, we find that the DEM is sensitive to noise on the biomarker trajectory parameters, resulting in an over estimation of the time taken for biomarker trajectories to go from normal to abnormal. This over estimate is approximately twice as long as the actual transition time of the trajectory for the expected noise level in neurodegenerative disease datasets. This simulation framework is equally applicable to a range of other models and longitudinal analysis techniques. PMID- 26356149 TI - Discriminating dysplasia: Optical tomographic texture analysis of colorectal polyps. AB - Optical projection tomography enables 3-D imaging of colorectal polyps at resolutions of 5-10 um. This paper investigates the ability of image analysis based on 3-D texture features to discriminate diagnostic levels of dysplastic change from such images, specifically, low-grade dysplasia, high-grade dysplasia and invasive cancer. We build a patch-based recognition system and evaluate both multi-class classification and ordinal regression formulations on a 90 polyp dataset. 3-D texture representations computed with a hand-crafted feature extractor, random projection, and unsupervised image filter learning are compared using a bag-of-words framework. We measure performance in terms of error rates, F measures, and ROC surfaces. Results demonstrate that randomly projected features are effective. Discrimination was improved by carefully manipulating various important aspects of the system, including class balancing, output calibration and approximation of non-linear kernels. PMID- 26356150 TI - A New Model for Estimating Peak Oxygen Uptake Based on Postexercise Measurements in Swimming. AB - PURPOSE: Assessing cardiopulmonary function during swimming is a complex and cumbersome procedure. Backward extrapolation is often used to predict peak oxygen uptake (VO2peak) during unimpeded swimming, but error can derive from a delay at the onset of VO2 recovery. The authors assessed the validity of a mathematical model based on heart rate (HR) and postexercise VO2 kinetics for the estimation of VO2peak during exercise. METHODS: 34 elite swimmers performed a maximal front crawl 200-m swim. VO2 was measured breath by breath and HR from beat-to-beat intervals. Data were time-aligned and 1-s-interpolated. Exercise VO2peak was the average of the last 20 s of exercise. Postexercise VO2 was the first 20-s average during the immediate recovery. Predicted VO2 values (pVO2) were computed using the equation: pVO2(t) = VO2(t) HRend-exercise/HR(t). Average values were calculated for different time intervals and compared with measured exercise VO2peak. RESULTS: Postexercise VO2 (0-20 s) underestimated VO2peak by 3.3% (95% CI = 9.8% underestimation to 3.2% overestimation, mean difference = -116 mL/min, SEE = 4.2%, P = .001). The best VO2peak estimates were offered by pVO2peak from 0 to 20 s (r2 = .96, mean difference = 17 mL/min, SEE = 3.8%). CONCLUSIONS: The high correlation (r2 = .86-.96) and agreement between exercise and predicted VO2 support the validity of the model, which provides accurate VO2peak estimations after a single maximal swim while avoiding the error of backward extrapolation and allowing the subject to swim completely unimpeded. PMID- 26356151 TI - The role of alkoxy radicals in the heterogeneous reaction of two structural isomers of dimethylsuccinic acid. AB - A key challenge in understanding the transformation chemistry of organic aerosols is to quantify how changes in molecular structure alter heterogeneous reaction mechanisms. Here we use two model systems to investigate how the relative locations of branched methyl groups control the heterogeneous reaction of OH with two isomers of dimethylsuccinic acid (C6H10O4). 2,2-Dimethylsuccinic acid (2,2 DMSA) and 2,3-dimethylsuccinic acid (2,3-DMSA) differ only in the location of the two branched methyl groups, thus enabling a closer inspection of how the distribution of carbon reaction sites impacts the chemical evolution of the aerosol. The heterogeneous reaction of OH with 2,3-DMSA (reactive OH uptake coefficient, gamma = 0.99 +/- 0.16) is found to be ~2 times faster than that of 2,2-DMSA (gamma = 0.41 +/- 0.07), which is attributed to the larger stability of the tertiary alkyl radical produced by the initial OH abstraction reaction. While changes in the average aerosol oxidation state (OSC) and the carbon number (NC) are similar for both isomers upon reaction, significant differences are observed in the underlying molecular distribution of reaction products. The reaction of OH with the 2,3-DMSA isomer produces two major reaction products: a product containing a new alcohol functional group (C6H10O5) formed by intermolecular hydrogen abstraction and a C5 compound formed via carbon-carbon (C-C) bond scission. Both of these reaction products are explained by the formation and subsequent reaction of a tertiary alkoxy radical. In contrast, the OH reaction with the 2,2-DMSA isomer forms four dominant reaction products, the majority of which are C5 scission products. The difference in the quantity of C-C bond scission products for these two isomers is unexpected since decomposition is assumed to be favored for the isomer with the most tertiary carbon sites (i.e. 2,3-DMSA). For both isomers, there is a much larger abundance of C6 alcohol relative to C6 ketone products, which suggests that the presence of the two branched methyl groups favors alkoxy formation from peroxy radical self reactions. These results reveal how the isomeric structure ultimately controls the overall competition between functionalization and fragmentation in these model systems. PMID- 26356152 TI - The effects of a Korean computer-based cognitive rehabilitation program on cognitive function and visual perception ability of patients with acute stroke. AB - [Purpose] The purpose of this study is to investigate the effects of a Korean computer-based cognitive rehabilitation program (CBCR) on the cognitive function and visual perception ability of patients with acute stroke. [Subjects] The subjects were 30 patients with acute stroke. [Methods] The subjects were randomly assigned to either the experimental group (EG) or the control group (CG). The EG subjects received CBCR with the CoTras program. The CG subjects received conventional cognitive rehabilitation. All subjects participated in a standard rehabilitation program according to a daily inpatient treatment schedule. In addition to standard rehabilitation, the subjects received 20 sessions (5 days a week for 4 weeks) of CBCR or conventional cognitive rehabilitation for 30 min. To compare the two groups, the Lowenstein Occupational Therapy Cognitive Assessment (LOTCA) and Motor-free Visual Perception Test-3 (MVPT-3) were performed. [Results] Both groups showed significant improvement in LOTCA and MVPT-3. Furthermore, there were significant differences in LOTCA and MVPT-3 between the two groups. [Conclusion] CBCR with CoTras may contribute toward the recovery of cognitive function and visual perception in patients with acute stroke. PMID- 26356153 TI - [Attention system functions and their relationship with self-reported health in patients with brain damage due to tumor]. AB - AIM: To compare parameters of attention in healthy people and patients with neoplasms in different regions of the cerebral cortex and to evaluate quality of life (QoL) indices with regard to impairment of different attention systems. MATERIAL AND METHODS: Twenty patients with oncological lesions of the brain (mean age 56.5+/-8.8 years) who did not undergo surgery were studied. Tumor localization was confirmed using contrast-enhanced computed tomography, the tumor type was histologically verified. A control group included 18 healthy people matched for age, sex and education level. To determine attention system functions, we developed a computed version of the Attention Network Test. Error rate and reaction time for correct responses to the target stimulus, displayed along with neutral, congruent and incongruent signals, were the indicators of the efficacy of selective processes. QoL indices were assessed using SF-36 health survey questionnaire. RESULTS AND CONCLUSION: The readiness to respond to incoming stimuli was mostly impaired in patients with brain tumors. Efficacy of executive attention, assessed as the increase in the number of errors in selection of visual stimuli, was decreased while temporary parameters of the functions of this system were not changed in patients compared to controls. The SF-36 total score was stable in patients with marked reduction in scores on the Role and Emotional Functioning scales. The most severe health impairment measured on the SF-36 scales of role/social emotional functioning and viability was recorded in patients with the lesions of frontal cortical areas compared to temporal/parietal areas. The relationship between SF-36 Health self-rating and attention systems was found. This finding puts the question of the importance of attention characteristics and QoL for survival prognosis of patients with brain tumors. PMID- 26356154 TI - [Prognostic criteria of rehabilitation of patients with ischemic stroke]. AB - AIM: To identify prognostic criteria of the restoration of movement in patients after acute disturbance of cerebral blood circulation. MATERIAL AND METHODS: Results of clinical examination of 82 patients after the acute disturbance of blood circulation in the left hemisphere were analyzed in the Center for Speech Pathology and Neurorehabilitation. The degree of hemiparesis was compared with disease history data, results of electroencephalography, ultrasound and transcranial dopplerography, computed tomography and biochemical study. RESULTS AND CONCLUSION: The volume of lesion <50 cm3 which was not located in occipital regions, the volume of lesion from 50 to 100 cm3 with the disturbance of blood circulation only in one arterial system (carotid or cerebral) and residual or moderate pathological changes in electrical activity were characteristic of favorable prognosis of rehabilitation. Poor prognosis was associated with the volume of lesion >100 cm3 with concomitant disturbance of blood circulation in two arterial systems (both carotid and cerebral), marked and moderate pathological changes in electrical activity and the occipital localization of the lesion regardless of its volume. PMID- 26356155 TI - [The anxiety-depressive spectrum disorders in patients with larynx diseases]. AB - AIM: To perform a psychopathological and clinical/psychological analysis of anxiety-depressive spectrum disorders (ADSD) in inflammatory otorhinolaryngological disease - larynx granuloma. MATERIAL AND METHODS: We examined 30 patients, aged 33-65 years, including 13 patients with post-surgical recurrence of granuloma and 17 patients diagnosed for the first time with granuloma. RESULTS AND CONCLUSION: The relationship between larynx granuloma and ADSD, predominantly of chronic type was shown. Prolonged psychotraumatic factors play a significant role in the development of ADSD. A role of anxiety in the ADSD structure as well as an importance of their diagnosis for a choice of therapeutic tactics was confirmed. Psychopharmacotherapy has led to a reduction in the frequency of granuloma relapses. The results confirmed the productivity of affective-stress model, based on the type of affectivity, in the analysis of ADSD. PMID- 26356156 TI - [Comorbidity of depressive disorders and coronary heart disease: general aspects of pathogenesis]. AB - AIM: The high level of comorbidity of coronary heart disease (CHD) and depressive disorders and general aspects of their pathogenesis is an actual problem of modern research. Authors studied the content of cholesterol, platelet serotonin, platelet aggregation, activity of pro-inflammatory markers in CHD patients with comorbid depressive disorders. MATERIAL AND METHODS: The study included 76 patients with CAD. The diagnosis of depressive disorder was set according to ICD 10, The Hamilton depression scales was used. RESULTS AND CONCLUSION: Depressive disorders in CHD patients were associated with an increase in the activity of pro inflammatory markers (IL-6 and TNF-alpha), and with high levels of low density lipoproteins. In patients with CAD and depressive disorders with high contents of platelet serotonin, the level of cholesterol was higher compared to those with low contents of serotonin. No significant differences in the functional platelet activity were identified in patients with CAD and comorbid depression compared to patients without mood disorders. PMID- 26356157 TI - [The multicenter non-interventional, prospective observational program on the study of practical use of teraligen in patients diagnosed with autonomic disorder (START2): a local Russian experience with the use of the Russian version of The Four-Dimensional Symptom Questionnaire (4DSQ). An intermediate analysis]. AB - AIM: To develop a new instrument able to identify pathological states and assess their changes during medication treatment. We aimed to study the typical practice of using alimemazine (teraligen) in patients with the diagnosis of autonomic nervous system disorder and to test the Russian version of @The Four-Dimensional Symptom Questionnaire@ (4DSQ) for measuring distress, depression, anxiety and somatization. MATERIAL AND METHODS: We examined 3053 patients (mean age 42.09 +/- 11.71 years) who received teraligen in doses gradually increasing from 5 to 15 mg per day. The observational program was carried out in over 600 outpatient clinics of the Russian Federation. The 4DSQ was administered before treatment and 4 weeks after treatment. The Clinical Global Impression (CGI) scale was used before, during (after 2 weeks) and after (4 weeks) treatment with teraligen. RESULTS AND CONCLUSION: There was a significant improvement of patient's state assessed both by physicians (CGI scale) and by patients (96 and 98%, respectively). The 4DSQ was sensitive to the parameters of response to treatment with teraligen: parameters obtained at baseline and 4 weeks after the beginning of treatment differed significantly demonstrating a significant decrease in distress, anxiety and somatization. PMID- 26356158 TI - [Dopamine receptor agonists: new forms and new possibilities in the treatment of Parkinson's disease]. AB - Main mechanisms of action of dopamine receptor agonists, efficacy of their use according to the results of earlier clinical trials and possible side-effects are discussed. The authors present their experience of prescription of rotigotine transdermal system in an open study of 30 patients with Parkinson's disease. The duration of the study was 8 weeks. There was a significant improvement of both motor and nonmotor (pain sensations, sleep, mood). The effective dose for treatment of initial stages was 4-6 mg daily and for the full-blown stage - 6-8 mg daily. The tolerability was good. PMID- 26356159 TI - [The principles of pharmacotherapy of poststroke shoulder pain]. AB - AIM: To analyze the results of examination and treatment of patients with poststroke shoulder pain. MATERIAL AND METHODS: The study included 213 patients who have had a stroke, including 16.4% patients with poststroke shoulder pain in early recovery period and 35.9% patients with poststroke shoulder pain in late recovery period. Therapeutic efficacy of amitriptyline, lidocaine (intravenously), pregabalin, tizanidine and non-steroid anti-inflammatory drugs was assessed. RESULTS AND CONCLUSION: Dysfunction of nervous system plays the main role in this pain syndrome. The efficacy of the drugs in the early/late recovery period was estimated as follows: nonsteroidal anti-inflammatory drugs - 33%/12%, amitriptyline - 24%/42%, gabapentin - 10%/13%, lidocaine - 95%/100%, tizanidine - 29%/33%. Seventy-six percent of patients were free of pain after treatment using a regimen suggested by the authors. PMID- 26356160 TI - [Zonisamid in additional treatment of pediatric partial epilepsy: a review of efficacy and safety in randomized double blind pacebo-controlled III phase study]. AB - AIM: To evaluate the efficacy and safety of zonisamid as add-on in treatment of partial epilepsy in children, aged 6 years and older, who received 1 or 2 antiepileptic drugs and its effect on their growth and development. MATERIAL AND METHODS: Children were randomized to treatment with zonisamid (n=107) or placebo (n=100). Dose was titrated beginning with 1mg/kg daily with a progressive increase to 8mg/kg. After the double-blind phase was completed, patients of the placebo group received zonisamid with the same titration rate and doses. The duration of the open phase was 45-57 weeks. The efficacy was assessed by the percentage of responders (reduction in the number of seizures by >= 50%) and patients who had not anymore seizures. The safety was evaluated by recording of side-effects, changes in laboratory parameters, neurological and somatic status and ECG. In the open phase, side-effects were recorded using the Tanner scale, bone age, behavioral scales, school records, verbal associative test. RESULTS: The percentage of responders was 50% in the zonisamid group and 31% in the placebo group, stopping of seizures was 14 and 3%, respectively. The efficacy of zonisamid remained over long time (more than one year): responders - 56,3%, stopping of seizures - 11% of patients. The total frequency of side-effects was similar in both groups (55,1 and 50%). The open phase did not reveal new adverse effects. Puberty and bone age did not change during one year of treatment. Zonisamid did not exert a negative effect on behavior and learning. Most of the patients and their parents evaluated the changes in the condition of the child as "marked improvement" or "very marked improvement". CONCLUSION: Zonisamid is an effective and well-tolerated medication as add-on in treatment of partial epilepsy in children aged 6 years and older. PMID- 26356161 TI - [An analysis of treatment of the Russian group of patients in the international observational study "Factors influencing response to botulinum toxin type A in patients with idiopathic cervical dystonia"]. AB - AIM: The analysis of the results of treatment of the Russian patient population in the frame of international, multicenter, non-interventional study of CD, the primary purpose of which was to determine the response rate to therapy with BTA at the peak of the effect: after one course of injections in settings of routine practice, as well as the results of application of modern definition for "response" to treatment with BTA. MATERIAL AND METHODS: In Russia 60 patients with idiopathic CD were included. Patients were classified as "responders" according to the following 4 criteria: effect size (improvement by >= 25% assessed by TWSTRS); effect duration: >= 12 weeks interval between the BTA injection and the day when the patient reported a decrease of clinical effect, indicating the need for repeated treatment; good tolerability of treatment (no treatment-related serious adverse events (AEs) during the study period); patient reported Clinical Global Improvement (CGI) score is +2 ("significant improvement") or +3 ("very significant improvement") at the visits 2 or 3. RESULTS AND CONCLUSION: In the Russian population, patients with a >= 25% improvement by TWSTRS scale at visit 2 (peak effect) accounted for 88.3%. Most of patients (81.6%) and physicians (81.7%) evaluated the efficacy of therapy as a "significant improvement" or "very significant improvement" by CGI. The criterion of the effect duration was achieved in 50% of cases. The BTA therapy was well tolerated (no severe AEs related to treatment) in 98.3% of patients. Overall, 40% of all patients met all the criteria for response to BTA treatment. According to the analysis of the general population, a high degree of response was observed for the effect size (73.6%), tolerability (97.5%) and patient-reported global clinical improvement (69.8%). Subjective assessment of the duration of the effect was achieved in 49.3% of patients, with 28.6% of patients considered as responders. Most patients met three of the four criteria. The proposed multifactorial definition of "response" may be of practical use for routine practice. PMID- 26356162 TI - [An assessment of cerebrolysin effect on BDNF level in patients with post stroke aphasia depending on carbohydrate metabolism disorders]. AB - AIM: We carried out an open randomized controlled study to explore the changes in the rate of speech recovery and BDNF concentrations in patients with left hemisphere stroke and carbohydrate metabolism disorders (diabetes mellitus type2 or prediabetes) who received cerebrolysin. MATERIAL AND METHODS: A study included 60 inpatients of the Center of Speech Pathology and Neurorehabilitation. Neuropsychological examination was performed at baseline and after the treatment was completed. We determined aphasia type and quantitatively assessed speech in scores which reflected the severity of speech impairment. BDNF serum concentrations were measured. RESULTS: Clinical efficacy of cerebrolysin (intravenously in dose 20 ml in 100 ml of physiological solution, 5 days a week, during 4 weeks) used in addition to standard neurorehabilitation measures in patients with post stroke aphasia of different severity was demonstrated. This treatment was most effective in patients with very marked and marked speech impairment that was confirmed by the maximal possible improvement of speech during the first course of neurorehabilitation measures, in particular in a subgroup of patients without carbohydrate metabolism disorders. A significant increase in BDNF concentrations was an additional evidence of this improvement. CONCLUSION: The use of cerebrolysin in the complex treatment of patients with post stroke aphasia of different severity improves the prognosis of their rehabilitation. PMID- 26356163 TI - [The effects of taurine on oxidative processes in brain edema]. AB - AIM: To investigate the free radical oxidation of lipids, oxidative modification of protein activity of glutathione peroxidase and glutathione reductase as well as the end product of nitric oxide - nitrite in the brain mitochondrial fraction of animals with experimentally induced cerebral edema and in treatment with taurine. MATERIAL AND METHODS: Toxic brain edema was induced in rats with intraperitoneal injection of tetra-ethyl lead (10 mg per kg of animal weight). The intensity of peroxidation was evaluated by hydroperoxide and malonic aldehyde contents. RESULTS: An analysis of the levels of oxidative modification of proteins revealed that brain edema was characterized by increased levels of oxidative modification of proteins and lipids, nitrogen oxide, reduced glutathione content and decrease in the activity of enzymes containing glutathione (glutathione peroxidase and glutathione reductase). CONCLUSION: On this basis, we suggested that drugs increasing glutathione content and activating enzymes containing glutathione, for example taurine, could be used as medications. The introduction of taurine in dose of 50 mg/kg during 5 days led to the reduction of lipid peroxidation products, normalization of oxidative modification of proteins in the mitochondrial fraction of the rats with experimental cerebral edema. PMID- 26356164 TI - [The 444G/A and -1021 C/T polymorphisms of the dopamine-beta-hydroxylase gene modulate the trajectory of alcohol dependence development]. AB - AIM: To study the influence of 444 G/A (rs 1108580) and -1021 C/T (rs 1611115) polymorphisms of the dopamine beta-hydroxylase (DBH) gene on clinical parameters of the trajectory of alcohol dependence. MATERIAL AND METHODS: Authors studied 548 male inpatients, of Slavic ethnicity, with ICD-10 diagnosis of "alcohol dependence" (F-10.2). RESULTS: The effects of DBH * 444 G/A on the rate of formation of alcohol withdrawal syndrome (AWS), and DBH *-1021C/T on the age of onset of alcohol abuse with significant role of the age of first alcohol use were identified. In 444 G/A GG carriers, the development of AWS was accelerated since the beginning of alcohol abuse compared with AA carriers (p=0.026), AG carriers occupied an intermediate position. In 22.5% of GG carriers, AWS developed within 2 years (AA: 8.11%, p=0.005; AG: 17.67%, p=0.04). According to the results of linear regression analysis, in AG carriers the alcohol abuse (p=0.037) and the AWS (p=0.049) developed earlier than in AA carriers if the first alcohol use occured at the age of about 15 years. Among -1021C/T genotype carriers who began to abuse alcohol at an early age (before 20 years), there were 23.45% patients with CC genotype and only 11.97% with a T allele (genotypes CT+TT) (p=0.03), but T carriers began to abuse alcohol earlier than others (p=0.05) if the first alcohol use occurred at the age of about 16 years. CONCLUSION: The results can be used to search for genetic markers for prognosis of alcohol dependence development. PMID- 26356165 TI - [Prediction of the changes of immunological status and psychopathological data in HIV-infected schizophrenia patients]. AB - AIM: To predict the immunological status in HIV-infected patients with schizophrenia based on a set of clinical and psychopathological characteristics of the endogenous process. MATERIAL AND METHODS: The study included 28 patients with confirmed diagnosis of schizophrenia and HIV status. Authors used psychopathological method, along with psychometric scales (PANSS), in patients with schizophrenia and an immunological method for the determination of HIV associated status and viral load. RESULTS: Affective syndromes with severe depressive symptoms, volitional impairment, high impulsivity and social features of autism can be prognostically favorable factors for the immune status of HIV infected patients with schizophrenia that obviously indicates an acute psychotic state. Negative (deficit) symptoms were prognostically unfavorable for the immune status of HIV-infected patients with schizophrenia and for psychosis course. CONCLUSION: Favorable immune status corresponds to acute psychosis whereas the forms with severe deficit are associated with immunosuppression in HIV-infected patients. PMID- 26356166 TI - [Gender and age dependent mortality from nervous diseases in Azerbaijan]. AB - AIM: To assess age- and sex-related changes in the mortality from nervous diseases at the population level. MATERIAL AND METHODS: Methods of descriptive statistics and analysis of qualitative traits were applied. We analyzed 13580 medical certificates of cause of death from nervous diseases (all classes of ICD 10). RESULTS: The mortality rate varied with age, the main trend of which was the dynamic growth. Age-specific mortality rates for men and women differed from each other: in most ages (20-24, 30-34, 45-49, 50-54, 55-59, 65-69), the likelihood of mortality was higher in men, and at the age of 5-9, 15-19, 60-64, 70 and more years in women. After the standardization of gender differences by age, the mortality risk of nervous illnesses disappeared (146.74 and 144.16 per 100 thousand for men and women, respectively). There were significant differences in the proportion of nervous diseases of all-cause mortality among the population in the groups stratified by age and sex. It is believed that situational factors is a cause of actual prevailing of gender age- and sex-related mortality risks. CONCLUSION: Gender features of age-related risk of mortality from nervous diseases are characterized by the multidirectional dynamics of likelihood of mortality and specific weight of nervous diseases among all causes of mortality. The actual gender features of age-related risk of mortality from nervous diseases are generally caused by situational factors (different age structure and unequal level of the general mortality among male and female population) which disappear after standardization. PMID- 26356167 TI - [International legal policy in the sphere of protection of the rights of people with mental disorders and Russian legislation]. AB - Protection of human rights is a matter of priority for the international and Russian legislation. The State is responsible for respect of corresponding principles. Main documents on human rights were accepted by the United Nations and then by the European Council and WHO. They were generalized to psychiatric patients as well. In the Russian Federation, the main law concerning the rights of people with mental disorders is the law "On Psychiatric Care and Guarantees of Citizens. Rights during Its Provision" (1992). The authors pointed out that some fields of its implementation are not adequately explored in comparison to international situation on the protection of rights of patients with mental disorders. PMID- 26356168 TI - [A role of stress-induced neuroendocrine disorders and tissue hypoxia in the thanatogenesis of traumatic intracranial hematomas]. AB - AIM: To study the dynamics of plasma concentration of stress hormones (ACTH and cortisol) and lactate as well as the integrative stress level indicator at neuroreanimation stage of severe cranial-brain injury. MATERIAL AND METHODS: Authors examined 34 patients with traumatic intracranial hematomas including 19 patients who died during the first two weeks after admission to the hospital and 15 patients who were discharged for outpatient treatment. To assess stress level, we used the indicator of stress level estimated as body mass x 1/3 x heart rate frequency x pulse pressure x 0,000126. Contents of blood plasma ACTH and cortisol were determined using radioimmune method, lactic acid was measured with enzyme colorimetric method. A control group included the indicators of 10 healthy people aged from 24 to 44 years. RESULTS AND CONCLUSION: In the first 24 h, the overstrain of the neuroendocrine system in response to strong stress influence of the trauma was noted in all patients. In patients with fatal outcome, an increase in cortisol in the first 24 h was excessive and lactate level was significantly higher during the observational period compared to the patients with favorable outcome. The peak of mortality was at 1-5 days when the stress level indicators, contents of ACTH, cortisol and lactate reached maximal values indicating the stress-induces overstrain of the hypothalamic- pituitary-adrenal axis and promoting the development of brain tissue hypoxia. PMID- 26356169 TI - [Clinical guidelines "Rational use of nonsteroidal anti-inflammatory drugs (NSAIDs) in clinical practice". Part II]. PMID- 26356170 TI - [Ecstatic seizures]. AB - Ecstatic seizures is a rare manifestation of epilepsy. They were described for the first time by F.M. Dostoevsky. Currently, the description of ecstatic seizures is possible to find in the scientific literature. The description of the own observation of a patient with emotional-affective seizures is presented. A role of the anterior insular cortex in the ecstatic seizures origin is discussed. The similarities between the feelings reported during ecstatic seizures and the feelings experienced under the effect of stimulant addictive drugs are described. The possible reasons of the low frequency of emotional-affective seizures are considered. PMID- 26356171 TI - [A modern concept of mixed dementia]. AB - Cognitive impairment is currently one of the most urgent problems. A number of newly registered cases of dementia in the world approaches to 7,7 millions that means that a new case of dementia arises every four seconds. According to WHO data, Western Europe is in the first place (appr. 7,0 millions of patients). In 2010, Russia was among 9 countries with the highest number of patients with dementia. Mixed dementia is characterized by the presence of one or several pathogenetic mechanisms of cognitive impairment. Its prevalence is about 45%. Neurodegenerative and vascular processes underlying dementia are mutually potentiated. An analysis of the majority of characteristics demonstrates that mixed dementia has characteristics of both Alzheimer's disease and vascular dementia. Disturbances of neurotransmitter systems are caused by cholinergic deficit. Galantamine (reminil) is the drug that has demonstrated its efficacy in the treatment of dementia of Alzheimer's type including dementia with chronic disturbances of cerebral blood circulation. PMID- 26356172 TI - Controlling release, unfolding and dissociation of membrane protein complexes in the gas phase through collisional cooling. AB - Mass spectrometry of intact membrane protein complexes requires removal of the detergent micelle by collisional activation. We demonstrate that the necessary energy can be obtained by adjusting the degree of collisional cooling in the ion source. This enables us to extend the energy regime for dissociation of membrane protein complexes. PMID- 26356173 TI - Recommendations for health-enhancing physical activities in type 2 diabetes patients. AB - [Purpose] Type 2 diabetes mellitus is a disease of civilization with epidemiological coverage. An integral component of a comprehensive process of type 2 diabetes mellitus prevention and treatment is reasonably proportioned exercise. The aim of the study was to evaluate the weekly physical activity of patients with type 2 diabetes mellitus and healthy subjects with respect to recommendations of the American College of Sports Medicine and American Diabetes Association. [Subjects] The study involved 31 patients with type 2 diabetes mellitus (treatment duration 9 +/- 0.8) and 31 healthy people. [Methods] Physical activity levels were determined by the International Physical Activity Questionnaire. A chi(2) test was applied to determine the percentage of people who met recommendations. [Results] Analysis of the obtained results demonstrated that the intensity of physical activity in patients with diabetes was moderate or low. The men in the control group met the recommendations for standard health related activities significantly more often than the patients with diabetes. In women, there was no such relationship, since most of the women were insufficiently physically active. [Conclusion] The conclusion to be drawn is that there is an urgent need to develop and implement effective programs to enhance physical activity among people at risk of diseases of civilization, including type 2 diabetes. PMID- 26356174 TI - Epigenetics in Kidney Transplantation: Current Evidence, Predictions, and Future Research Directions. AB - Epigenetic modifications are changes to the genome that occur without any alteration in DNA sequence. These changes include cytosine methylation of DNA at cytosine-phosphate diester-guanine dinucleotides, histone modifications, microRNA interactions, and chromatin remodeling complexes. Epigenetic modifications may exert their effect independently or complementary to genetic variants and have the potential to modify gene expression. These modifications are dynamic, potentially heritable, and can be induced by environmental stimuli or drugs. There is emerging evidence that epigenetics play an important role in health and disease. However, the impact of epigenetic modifications on the outcomes of kidney transplantation is currently poorly understood and deserves further exploration. Kidney transplantation is the best treatment option for end-stage renal disease, but allograft loss remains a significant challenge that leads to increased morbidity and return to dialysis. Epigenetic modifications may influence the activation, proliferation, and differentiation of the immune cells, and therefore may have a critical role in the host immune response to the allograft and its outcome. The epigenome of the donor may also impact kidney graft survival, especially those epigenetic modifications associated with early transplant stressors (e.g., cold ischemia time) and donor aging. In the present review, we discuss evidence supporting the role of epigenetic modifications in ischemia-reperfusion injury, host immune response to the graft, and graft response to injury as potential new tools for the diagnosis and prediction of graft function, and new therapeutic targets for improving outcomes of kidney transplantation. PMID- 26356175 TI - Computed Tomography Volumetry in Preoperative Living Kidney Donor Assessment for Prediction of Split Renal Function. AB - BACKGROUND: Transplant centers commonly evaluate split renal function (SRF) with Tc-99m-mercapto-acetyltriglycin (MAG3) scintigraphy in living kidney donation. Alternatively, the kidney volume can be measured based on predonation CT scans. The aim of this study was to identify the most accurate CT volumetry technique for SRF and the prediction of postdonation kidney function (PDKF). METHODS: Three CT volumetry techniques (modified ellipsoid volume [MELV], smart region of interest [ROI] volume, renal cortex volume [RCV]) were performed in 101 living kidney donors. Preoperation CT volumetric SRF was determined and compared with MAG3-SRF, postoperation donor kidney function, and graft function. RESULTS: The correlation between donors predonation total kidney volume and predonation kidney function was the highest for RCV (0.58 with creatine clearance, 0.54 with estimated glomerular filtration rate-Cockcroft-Gault). The predonation volume of the preserved kidney was (ROI, MELV, RCV) 148.0 +/- 29.1 cm, 151.2 +/- 35.4 and 93.9 +/- 25.2 (P < 0.005 MELV vs RCV and ROI vs RCV). Bland-Altman analysis showed agreement between CT volumetry SRF and MAG3-SRF (bias, 95% limits of agreement: ROI vs MAG3 0.4%, -7.7% to 8.6%; MELV vs MAG3 0.4%, -8.9% to 9.7%; RCV vs MAG3 0.8%, -9.1% to 10.7%). The correlation between predonation CT volumetric SRF of the preserved kidney and PDKF at day 3 was r = 0.85 to 0.88, between MAG3 SRF and PDKF (r = 0.84). The difference of predonation SRF between preserved and donated kidney was the lowest for ROI and RCV (median, 3% and 4%; 95th percentile, 9% and 13%). CONCLUSIONS: Overall renal cortex volumetry seems to be the most accurate technique for the evaluation of predonation SRF and allows a reliable prediction of donor's PDKF. PMID- 26356176 TI - Defective CD8 Signaling Pathways Delay Rejection in Older Recipients. AB - CD8+ T cells play a cardinal feature in response to alloantigens and are able to generate effector/memory T cells independently from CD4+ T cells. To investigate the impact of aging on CD8 T cells, we used a fully mismatched mouse skin transplant model. Our findings showed a prolonged allograft survival in older recipients associated with a significant increase of CD4+ and CD8+ CD44high CD62Llow effector/memory T cells and a reduced systemic IFNgamma production. When reconstituting young CBA Rag-1 mice that lack mature T and B cells with old CD8+ T cells expressing clonal anti-H2K T cell receptor (TCR) alloreactive for MHC I, graft survival was significantly prolonged and comparable to those receiving young CD8+ T cells. Moreover, our data showed that reduced systemic IFNgamma levels observed in old recipients had been linked to a compromised expression of the IL-2R beta subunit (CD122) by old CD8+ T cells. In addition, we observed an impaired IFNgamma production on IL-2 receptor activation. At the same time, gene profiling analysis of old CD8 T cells demonstrated reduced chemokine ligand-3 and CD40L expression that resulted in compromised CD8+ T cell/dendritic cell communication, leading to impaired migratory and phagocytic activity of CD11c cells.Collectively, our study demonstrated that aging delays allograft rejection. CD8 T cells play a critical role in this process linked to a compromised production of IFNgamma, in addition to a defective IL-2 receptor signaling machinery and a defective communication between CD8 T cells and dendritic cells. PMID- 26356177 TI - Active Education, Keeping It Personal and Making It Easy: A Potential Path to Increasing Donors. PMID- 26356178 TI - Community-Based Interventions and Individuals' Willingness to be a Deceased Organ Donor: Systematic Review and Meta-Analysis. AB - BACKGROUND: Widespread in-principle community support for organ donation does not necessarily translate to individuals becoming organ donors after death. Previous studies have identified factors that influence individuals' decisions to become organ donors, which may be effectively targeted by interventions. We aimed to describe and evaluate the effectiveness of community-based interventions to increase the willingness of individuals to be a deceased organ donor. METHODS: We systematically reviewed all randomized controlled trials (RCTs), non-RCTs (NRCTs), and before-after studies that assessed the impact of interventions on increasing the willingness to be a deceased organ donor (measured as commitment to donate and/or intention to donate). We searched MEDLINE, Embase, PsycINFO, and CINAHL, without language restriction, to December 2013 and the reference lists of the included articles. We conducted a risk of bias assessment using the Cochrane risk of bias tools and assessed confidence in the evidence using the Grading of Recommendations Assessment, Development, and Evaluation framework. RESULTS: We identified 63 studies (11 RCTs, 8 cluster-RCTs, 4 NRCTs, 8 cluster-NRCTs, 27 before-after studies) with over 170,000 participants. Overall, the quality of the evidence was low. Participants who received a broad range of community-based interventions were more likely to commit as donors (7 cluster-RCTs; 6015 participants; relative risk, 1.70; 95% confidence interval [95% CI], 1.22-2.36; I = 94%, P = 0.002), and had higher levels of willingness to donate (3 RCTs, 393 participants; standardized mean difference, 0.29; 95% CI, 0.01-0.56; I = 45%; P = 0.04) than those who did not receive the interventions, but not the intention to donate (315 participants; relative risk, 1.19; 95% CI, 0.94-1.51; P = 0.14). CONCLUSIONS: Community partnerships and active learning community-based interventions may be effective in increasing the commitment, but not intentions to donate. However, the overall risk of bias for was high, and this may have led to overestimation of the relative treatment effects of these interventions. PMID- 26356180 TI - Temperature response of methane production in liquid manures and co-digestates. AB - Intensification of livestock production makes correct estimation of methanogenesis in liquid manure increasingly important for inventories of CH4 emissions. Such inventories currently rely on fixed methane conversion factors as knowledge gaps remain with respect to detailed temperature responses of CH4 emissions from liquid manure. Here, we describe the temperature response of CH4 production in liquid cattle slurry, pig slurry, and fresh and stored co-digested slurry from a thermophilic biogas plant. Subsamples of slurry were anoxically incubated at 20 temperatures from 5-52 degrees C in a temperature gradient incubator and CH4 production was measured by gas chromatographic analysis of headspace gas after a 17-h incubation period. Methane production potentials at 5 37 degrees C were described by the Arrhenius equation (modelling efficiencies, 79.2-98.1%), and the four materials showed a consistent activation energy (Ea) which averaged 81.0kJmol(-1) (95% confidence interval, 74.9-87.1kJmol(-1)) corresponding to a temperature sensitivity (Q10) of 3.4. In contrast, the frequency factor (A) differed among the slurry materials (30.11 for As in drinking water, vegetables and rice, for Mn in drinking water, vegetables, rice and wheat, for Pb in rice and wheat indicated the potential health risk to the local population. An assessment of As and other elements of other food components should be conducted to understand the actual health hazards caused by ingestion of food in people residing in the middle Gangetic plain. PMID- 26356186 TI - Microbiote shift in the Medicago sativa rhizosphere in response to cyanotoxins extract exposure. AB - The bloom-containing water bodies may have an impact due to cyanotoxins production on other microorganisms and aquatic plants. Where such water is being used for crops irrigation, the presence of cyanotoxins may also have a toxic impact on terrestrial plants and their rhizosphere microbiota. For that purpose, PCR-based 454 pyrosequencing was applied to phylogenetically characterize the bacterial community of Medicago sativa rhizosphere in response to cyanotoxins extract. This analysis revealed a wide diversity at species level, which decreased from unplanted soil to root tissues indicating that only some populations were able to compete for nutrients and niches in this selective habitat. Gemmatimonas, Actinobacteria, Deltaproteobacteria and Opitutae mainly inhabited the bulk soil, whereas, the root-adhering soil and the root tissues were inhabited by Gammaproteobacteria and Alphaproteobacteria. The proportion of these populations fluctuated in response to cyanotoxins extract exposure. Betaproteobacteria proportion increased in the three studied compartments, whereas Gammaproteobacteria proportion decreased except in the bulk soil. This study revealed the potential toxicity of cyanotoxins extract towards Actinobacteria, Gemmatimonas, Deltaproteobacteria, and Gammaproteobacteria, however Clostridia, Opitutae and bacteria related with Betaproteobacteria, were stimulated denoting their tolerance. Altogether, these data indicate that crop irrigation using cyanotoxins containing water might alter the rhizosphere functioning. PMID- 26356187 TI - Observation of correlated spin-orbit order in a strongly anisotropic quantum wire system. AB - Quantum wires with spin-orbit coupling provide a unique opportunity to simultaneously control the coupling strength and the screened Coulomb interactions where new exotic phases of matter can be explored. Here we report on the observation of an exotic spin-orbit density wave in Pb-atomic wires on Si(557) surfaces by mapping out the evolution of the modulated spin-texture at various conditions with spin- and angle-resolved photoelectron spectroscopy. The results are independently quantified by surface transport measurements. The spin polarization, coherence length, spin dephasing rate and the associated quasiparticle gap decrease simultaneously as the screened Coulomb interaction decreases with increasing excess coverage, providing a new mechanism for generating and manipulating a spin-orbit entanglement effect via electronic interaction. Despite clear evidence of spontaneous spin-rotation symmetry breaking and modulation of spin-momentum structure as a function of excess coverage, the average spin polarization over the Brillouin zone vanishes, indicating that time-reversal symmetry is intact as theoretically predicted. PMID- 26356188 TI - Inflammatory Myofibroblastic Tumor of the Liver: A Diagnostic Challenge. AB - Inflammatory myofibroblastic tumor (IMT) is an uncommon myofibroblastic neoplasm that was formerly included within the broad category of inflammatory pseudotumor (IPT). IMT is rarely encountered in the liver. Similar to IMT of other organs, the interchangeable use of the terms IMT and IPT in liver has made the analysis of these lesions difficult. In this review, clinical and pathological features of IMT of the liver are reviewed and the differential diagnosis of IMT is discussed, with emphasis on IPT and the other entities included in this large category. IMT can mimic malignant tumors. There are no known unique diagnostic clinical, laboratory, or radiological features. The definitive diagnosis of IMT depends on careful pathological examination. The histopathological evaluation of hepatic IMT reveals that, the myxoid/vascular pattern is the most frequently observed, followed by, in decreasing frequency, fibrous histiocytoma-like pattern and hypocellular fibrous pattern. In IMT of the liver, anaplastic lymphoma kinase (ALK) expression reliably predicts the presence of an ALK gene rearrangement. The diagnosis of hepatic IMT depends on the dominant histopathological pattern, and the management of the disease is still controversial. IMT of the liver is a distinctive neoplasm of intermediate biological potential, and should be distinguished from the variety of lesions that are included under the broad category of IPT. Therefore, to avoid confusion regarding the true incidence and behavior of hepatic IMT, the term IPT should not be used interchangeably with IMT. The rarity of IMT in liver should not minimize its consideration in the differential diagnosis of liver tumors, especially in patients with tumor markers in normal range. PMID- 26356189 TI - Ultrafast Photodetection in the Quantum Wells of Single AlGaAs/GaAs-Based Nanowires. AB - We investigate the ultrafast optoelectronic properties of single Al0.3Ga0.7As/GaAs core-shell nanowires. The nanowires contain GaAs-based quantum wells. For a resonant excitation of the quantum wells, we find a picosecond photocurrent which is consistent with an ultrafast lateral expansion of the photogenerated charge carriers. This Dember-effect does not occur for an excitation of the GaAs-based core of the nanowires. Instead, the core exhibits an ultrafast displacement current and a photothermoelectric current at the metal Schottky contacts. Our results uncover the optoelectronic dynamics in semiconductor core-shell nanowires comprising quantum wells, and they demonstrate the possibility to use the low-dimensional quantum well states therein for ultrafast photoswitches and photodetectors. PMID- 26356191 TI - Overlap of Acute Cholecystitis with Gallstones and Squamous Cell Carcinoma of the Gallbladder in an Elderly Patient. AB - Introduction. The incidence of gallbladder cancer presenting with acute cholecystitis is 2.3%, squamous cell carcinoma is rarely seen, and overlap of acute cholecystitis and squamous cell carcinoma is a very rare condition in the literature. Presentation of Case. A 75-year-old woman was admitted to emergency service with a pain in the right upper quadrant, nausea, and vomiting. The patient was considered as having acute cholecystitis. During the exploration because Hartman's pouch was not dissected, it was adhered to the cystic duct and had fibrotic adhesion. It could not be understood whether this adhesion was a tumor or a fibrotic tumor and thus we performed cholecystectomy with a 1 cm resection of the choledochus. Pathological examination revealed the presence of (R0), T1 N0 M0 squamous cell carcinoma with clean resection borders and there was no in tumor five dissected lymph nodes. The patient has been followed up for about two years and no clinical problem has been observed throughout the follow up. Discussion. Acute cholecystitis with gallstones may overlap with gallbladder cancer and generally presents nonspecific symptoms. No additional imaging techniques were performed since no clinical sign except for the wall thickening was detected and no suspected malignancy such as mass was detected on USG. Squamous cell carcinoma of the gallbladder shows poor diagnosis, but since its overlap with cholecystitis presents early symptoms and thus leads to early diagnosis and effective treatment, the localization of the carcinoma is of prime importance. Conclusion. Gallbladder cancer should be kept in mind in elderly patients with acute cholecystitis. PMID- 26356190 TI - The ABCC6 Transporter as a Paradigm for Networking from an Orphan Disease to Complex Disorders. AB - The knowledge on the genetic etiology of complex disorders largely results from the study of rare monogenic disorders. Often these common and rare diseases show phenotypic overlap, though monogenic diseases generally have a more extreme symptomatology. ABCC6, the gene responsible for pseudoxanthoma elasticum, an autosomal recessive ectopic mineralization disorder, can be considered a paradigm gene with relevance that reaches far beyond this enigmatic orphan disease. Indeed, common traits such as chronic kidney disease or cardiovascular disorders have been linked to the ABCC6 gene. While during the last decade the awareness of the wide ramifications of ABCC6 has increased significantly, the gene itself and the transmembrane transporter it encodes have not unveiled all of the mysteries that surround them. To gain more insights, multiple approaches are being used including next-generation sequencing, computational methods, and various "omics" technologies. Much effort is made to place the vast amount of data that is gathered in an integrated system-biological network; the involvement of ABCC6 in common disorders provides a good view on the wide implications and potential of such a network. In this review, we summarize the network approaches used to study ABCC6 and the role of this gene in several complex diseases. PMID- 26356193 TI - Surface Modification for Superhydrophilicity and Underwater Superoleophobicity: Applications in Antifog, Underwater Self-Cleaning, and Oil-Water Separation. AB - A facile yet effective surface modification strategy for superhydrophilicity and underwater superoleophobicity was developed by silanization of zwitterionic sulfobetaine silane (SBSi) on oxidized surfaces. The coatings exhibit excellent wetting properties, as indicated by static contact angles of <5 degrees , and long-term stability under exposure to heat and UV irradiation. The SBSi-modified surfaces were employed for applications in antifog, self-cleaning, and oil-water separation. The SBSi glasses retained their optical transmittance because of the rapid formation of coalesced water thin films on surfaces in contact with water vapor and moisture. In addition, the underwater-oil contact-angle measurements verified the underwater superoleophobicity of the zwitterionic SBSi coatings. The oil spills on the SBSi coating could be readily removed in contact with water to realize the self-cleaning property. Besides, we modified stainless steel wire meshes with SBSi for oil-water separation. The optimal oil recovery rate for the oil-water mixtures reached >99.5% when using the SBSi-coated meshes with a pore size of 17 MUm. More importantly, the water flux with modified meshes achieved 6.5 * 10(7) L/m(2).h.bar, enabling gravity-driven and energy-saving separation. Consequently, we demonstrated the superhydrophilicity and underwater superoleophobicity of SBSi, offering promise in solving technological problems of interfacial fog, oil spills, and oil-water separation and thereby showing great potential in large-scale commercial applications. PMID- 26356192 TI - Coping strategies in a sample of anxiety patients: factorial analysis and associations with psychopathology. AB - BACKGROUND: The relationship between coping styles and mental disorders has received considerable attention and instruments have been developed to assess coping strategies. The measurement by means of category systems has been criticized and a functional hierarchy of action types linked to the adaptive processes is preferred. We aimed to determine which factors may exist within the Brief-COPE (Brief Coping Orientation to Problems Experienced--COPE--Inventory) in an Italian sample of patients with anxiety disorders; and if these factors correlate with the severity of psychopathology or with other characteristics. METHODS: A total sample of 148 patients was recruited. The Brief-COPE inventory, the Symptom Check List 90-Revised, the Penn State Worry Questionnaire, the Zung Anxiety Status Inventory and the Zung Self-Rating Anxiety Scale were administered. RESULTS: Factor analysis of the Brief-COPE yielded nine factors accounting for 65.48% of the variance. Patients scored higher on Searching Support, followed by Acceptance, Changing Perspective, and Problem Solving. Associations between measures of psychopathology and factors of coping strategies, mostly Searching support and Avoidance, were found. CONCLUSIONS: Data of the present study support a nine-factor structure of the Brief-COPE that includes five broad dimensions of coping. Psychopathology was mostly related to Searching support and Avoidance factors, showing that these strategies may reflect ineffective ways of coping; Problem solving and Changing perspective could be a valid approach to moderate anxiety/depression symptoms and psychopathology in general. PMID- 26356200 TI - Sequence Diversity of VP4 and VP7 Genes of Human Rotavirus Strains in Saudi Arabia. AB - Group A rotavirus is responsible for inducing severe diarrhea in young children worldwide. Rotavirus vaccines are used to control the disease in many countries. In the current study, the sequences of human rotavirus G and P types in Saudi Arabia are reported and compared to different relevant published sequences. In addition, the VP4 and VP7 genes of the G1P[8] strains are compared to different antigenic epitopes of the rotavirus vaccines. Stool samples were collected from children under 2 years suffering from severe diarrhea. Screening of the rotavirus positive samples was performed with rapid antigen detection kit. RNA was amplified from rotavirus-positive samples by reverse transcriptase polymerase chain reaction assay for both VP4 and VP7 genes. Direct sequencing of the VP4 and VP7 genes was conducted and the obtained sequences were compared to each other and to the rotavirus vaccines. Both G1P[8] G1P[4] genotypes were detected. Phylogenetic analysis revealed that the detected strains belong to G1 lineage 1 and 2, P[8] lineage 3, and to P[4] lineage 5. Multiple amino acid substitutions were detected between the Saudi RVA strains and the commonly used vaccines. The current findings emphasize the importance of the continuous surveillance of the circulating rotavirus strains, which is crucial for monitoring virus evolution and helping in predicting the protection level afforded by rotavirus vaccines. PMID- 26356194 TI - Latent virus infection upregulates CD40 expression facilitating enhanced autoimmunity in a model of multiple sclerosis. AB - Epstein-Barr virus (EBV) has been identified as a putative environmental trigger of multiple sclerosis (MS) by multiple groups working worldwide. Previously, we reported that when experimental autoimmune encephalomyelitis (EAE) was induced in mice latently infected with murine gamma-herpesvirus 68 (gammaHV-68), the murine homolog to EBV, a disease more reminiscent of MS developed. Specifically, MS-like lesions developed in the brain that included equal numbers of IFN-gamma producing CD4(+) and CD8(+) T cells and demyelination, none of which is observed in MOG induced EAE. Herein, we demonstrate that this enhanced disease was dependent on the gammaHV-68 latent life cycle and was associated with STAT1 and CD40 upregulation on uninfected dendritic cells. Importantly, we also show that, during viral latency, the frequency of regulatory T cells is reduced via a CD40 dependent mechanism and this contributes towards a strong T helper 1 response that resolves in severe EAE disease pathology. Latent gamma-herpesvirus infection established a long-lasting impact that enhances subsequent adaptive autoimmune responses. PMID- 26356201 TI - Highly Selective Cascade C-C Bond Formation via Palladium- Catalyzed Oxidative Carbonylation-Carbocyclization-Carbonylation-Alkynylation of Enallenes. AB - A highly efficient palladium-catalyzed oxidative cascade reaction of enallenes undergoing overall four C-C bond formations has been developed. The insertion cascade proceeds via carbonylation-carbocyclization-carbonylation-alkynylation involving sequential insertion of carbon monoxide, olefin, and carbon monoxide. Furthermore, different types of terminal alkynes and functionalized enallenes have been investigated and found to undergo the cascade reaction under mild reaction conditions. PMID- 26356203 TI - Synthesis and stability of cyclic alpha-hydrogen nitroxides. AB - Nitroxides (nitroxyl radicals) hold a unique place in science due to their stable radical nature. We have recently reported the first design concept providing a general solution to the problem of designing and preparing monocyclic alpha hydrogen nitroxides. The initial studies were limited to aryl derivatives. We now report a wider study showing that alkyl substituents may be employed as well. In addition, we report several additional examples of aryl substituents and reveal some of the structural limitations with regard to nitroxide stability as a function of the alpha-carbon substituent. PMID- 26356202 TI - Controlled Co-reconstitution of Multiple Membrane Proteins in Lipid Bilayer Nanodiscs Using DNA as a Scaffold. AB - Nanodiscs constitute a tool for the solubilization of membrane proteins in a lipid bilayer, thus offering a near-native membrane environment. Many membrane proteins interact with other membrane proteins; however, the co-reconstitution of multiple membrane proteins in a single nanodisc is a random process that is adversely affected by several factors, including protein aggregation. Here, we present an approach for the controlled co-reconstitution of multiple membrane proteins in a single nanodisc. The temporary attachment of designated oligonucleotides to individual membrane proteins enables the formation of stable, detergent-solubilized membrane protein complexes by base-pairing of complementary oligonucleotide sequences, thus facilitating the insertion of the membrane protein complex into nanodiscs with defined stoichiometry and composition. As a proof of principle, nanodiscs containing a heterodimeric and heterotrimeric membrane protein complex were reconstituted using a fluorescently labeled voltage gated anion channel (VDAC) as a model system. PMID- 26356204 TI - The Capacity to Manage Orthopaedic Trauma. PMID- 26356205 TI - Wrong Place, Wrong Time: Coincidental Involvement in the Gujarat Earthquake, India (2001). AB - Orthopaedic surgeons have traditionally answered the call in times of disaster. Shortly after the devastating earthquake in January 2001, in Gujarat India, that call came from a buffer zone hospital. The Gandhi Lincoln Hospital in Deesa, Gujarat was struggling with an influx of injured survivors. Five days after the initial event, 2 of the traveling American authors met up with the Director of Surgery at the hospital. The clinical load was primarily extremity injuries and wounds. The authors present their assessment of the orthopaedic response highlighting factors of success, barriers, and lessons learned. Despite their published accounts, many of these lessons were not applied to the Haiti earthquake response. PMID- 26356206 TI - Building the Capacity to Manage Orthopaedic Trauma After a Catastrophe in a Low Income Country. AB - Providing trauma care in an austere environment is very challenging, especially when the country is faced with a natural disaster. Unfortunately the combination of these elements highlights the deficiencies in managing orthopaedic trauma both in a developing country and in the face of a natural disaster, exponentially amplifying the effects of each. When considering the implementation and practice of orthopaedic trauma care in such an environment, one must consider the initial phase of program development and look further to the future in the development of a resilient program, which is sustainable. Through the use of the example of Haiti and a specific Non-Governmental Organization, we discuss the evidence for and thoughts behind developing orthopaedic trauma care program immediately after a natural disaster. This program aims to build capacity and empower a developing nation's health professionals to advance the care of orthopaedic trauma patients. We describe a model of capacity building that serves as a framework to highlight the strengths and weaknesses of low-to middle-income countries in providing orthopaedic trauma care when faced with such a challenge. PMID- 26356207 TI - Building Orthopaedic Trauma Capacity: IGOT International SMART Course. AB - Orthopaedic injuries from trauma are increasingly common in Low to Middle Income Countries secondary to the increase in road traffic. These injuries commonly contain a soft tissue component, which complicates treatment of bony injuries and increases amputation rate. Specialized care using plastic surgery techniques is required to effectively treat these injuries. Historically medical mission models have been used to provide specialists to help provide soft tissue coverage where plastic surgeons are not available. This type of care is inherently unsustainable. We present an approach where a course was designed to teach soft tissue coverage techniques to orthopaedic surgeons. The course was given annually over 5 years, serving approximately 300 participants. Data collected from participants demonstrated that they found the course useful, learned techniques that allowed them to care for patients, and disseminate the knowledge further. Participants endorsed that they had performed 594 flaps with a 93% success rate at 1 year of follow-up from the course. We find that this type of intervention has the potential to address the need for soft tissue coverage in countries where this need is present, and resources are unavailable. PMID- 26356208 TI - INternational ORthopaedic MUlticentre Study (INORMUS) in Fracture Care: Protocol for a Large Prospective Observational Study. AB - Despite the fact that orthopaedic trauma injuries represent a serious cause of mortality and morbidity worldwide, there are few data in low-middle income countries quantifying the burden of fractures and describing current treatment practices. To address this critical knowledge gap, a large multinational prospective observational study of 40,000 patients with musculoskeletal trauma in Africa, Asia, and Latin America is proposed. The International Orthopaedic Multicentre Study in Fracture Care (INORMUS) study seeks to determine the incidence of major complications (mortality, reoperation, and infection) within 30 days after a musculoskeletal injury and to determine patient, treatment, and system factors associated with these major complications in low-middle income countries. This study coincides with the World Health Organization's Global Road Traffic Safety Decade (2011-2020) and other international efforts to reduce the burden of injury on developing populations. Insight gained from the INORMUS study will not only inform the global burden of orthopaedic trauma but also drive the development of future randomized trials to evaluate simple solutions and practical interventions to decrease deaths and improve the quality of life for trauma patients worldwide. PMID- 26356209 TI - Developing Orthopaedic Trauma Capacity in Uganda: Considerations From the Uganda Sustainable Trauma Orthopaedic Program. AB - Uganda, like many low-income countries, has a tremendous volume of orthopaedic trauma injuries. The Uganda Sustainable Trauma Orthopaedic Program (USTOP) is a partnership between the University of British Columbia and Makerere University that was initiated in 2007 to reduce the consequences of neglected orthopaedic trauma in Uganda. USTOP works with local collaborators to build orthopaedic trauma capacity through clinical training, skills workshops, system support, technology development, and research. USTOP has maintained a multidisciplinary approach to training, involving colleagues in anaesthesia, nursing, rehabilitation, and sterile reprocessing. Since the program's inception, the number of trained orthopaedic surgeons practicing in Uganda has more than doubled. Many of these newly trained surgeons provide clinical care in the previously underserved regional hospitals. The program has also worked with collaborators to develop several technologies aimed at reducing the cost of providing orthopaedic care without compromising quality. As orthopaedic trauma capacity in Uganda advances, USTOP strives to continually evolve and provide relevant support to colleagues in Uganda. PMID- 26356210 TI - The American Academy of Orthopaedic Surgeons/Society of Military Orthopaedic Surgeons/Orthopaedic Trauma Associations/Pediatric Orthopaedic Association Disaster Response and Preparedness Course. AB - A disaster is a catastrophic event that disrupts normal infrastructure to such a degree that normal response mechanisms and capabilities cannot manage what is required to respond appropriately to the event. Launched after the largest urban disaster in modern history--the 2010 Haiti Earthquake--the American Academy of Orthopaedic Surgeons/Society of Military Orthopaedic Surgeons/Orthopaedic Trauma Association/Pediatric Orthopaedic Association of North America (AAOS/SOMOS/OTA/POSNA) Disaster Response Course (DRC) is designed to prepare orthopaedic surgeons for service in disaster response and humanitarian assistance efforts in both the acute phases as well as in the recovery and reconstructions phases. To date, 395 orthopaedic surgeons have completed the DRC and 286 (72.4%) have opted to become registered disaster responders. PMID- 26356211 TI - Orthopaedic Trauma Care Specialist Program for Developing Countries. AB - The dire challenges faced in Haiti, both preearthquake and postearthquake, highlight the need for developing surgical infrastructure to care for traumatic musculoskeletal injuries. The proposed Orthopaedic Trauma Care Specialist (OTCS) residency program aims to close the critical human resource gap that limits the appropriate care of musculoskeletal trauma in Haiti. The OTCS program is a proposal for a 2-year residency program that will focus primarily on the management of orthopaedic trauma. The proposed program will be a comprehensive approach for implementing affordable and sustainable strategies to improve orthopaedic trauma care. Its curriculum will be tailored to the injuries seen in Haiti, and the treatments that can be delivered within their health care system. Its long-term sustainability will be based on a "train-the-trainers" approach for developing local faculty to continue the program. This proposal outlines the OTCS framework specifically for Haiti; however, this concept is likely applicable to other low- and middle-income environments in a similar need for improved trauma and fracture care. PMID- 26356212 TI - Making Safe Surgery Affordable: Design of a Surgical Drill Cover System for Scale. AB - Many surgeons in low-resource settings do not have access to safe, affordable, or reliable surgical drilling tools. Surgeons often resort to nonsterile hardware drills because they are affordable, robust, and efficient, but they are impossible to sterilize using steam. A promising alternative is to use a Drill Cover system (a sterilizable fabric bag plus surgical chuck adapter) so that a nonsterile hardware drill can be used safely for surgical bone drilling. Our objective was to design a safe, effective, affordable Drill Cover system for scale in low-resource settings. We designed our device based on feedback from users at Mulago Hospital (Kampala, Uganda) and focused on 3 main aspects. First, the design included a sealed barrier between the surgical field and hardware drill that withstands pressurized fluid. Second, the selected hardware drill had a maximum speed of 1050 rpm to match common surgical drills and reduce risk of necrosis. Third, the fabric cover was optimized for ease of assembly while maintaining a sterile technique. Furthermore, with the Drill Cover approach, multiple Drill Covers can be provided with a single battery-powered drill in a "kit," so that the drill can be used in back-to-back surgeries without requiring immediate sterilization. The Drill Cover design presented here provides a proof of-concept for a product that can be commercialized, produced at scale, and used in low-resource settings globally to improve access to safe surgery. PMID- 26356213 TI - Simplified Negative Pressure Wound Therapy Device for Application in Low-Resource Settings. AB - Negative pressure wound therapy (NPWT) provides proven wound healing benefits and is often a desirable wound treatment methodology. Unfortunately, NPWT devices are not widely available in low-resource settings. To overcome the identified NPWT barriers, a simplified NPWT (sNPWT) system was designed and iteratively improved during field-based testing. The sNPWT technology, our device design iterations, and the design-based results of our field tests are described in this article. The sNPWT system includes a bellows hand pump, an occlusive drape, and a tube with tube connectors, connecting the drape to the pump. The most critical property of an sNPWT system is that it must be airtight. The details of the design iterations, which are needed to achieve an occlusive system, are explained. During the design process, the sNPWT system was tested during the earthquake relief in Haiti. This testing found that a liquid sealant was necessary to seal the drape to the periwound skin. A study conducted in Rwanda verified that a liquid latex sealant was safe to use, and that the tube connector must be connected to the drape with an airtight method during the manufacturing process. This work has shown that sNPWT is feasible in low-resource settings. Since the completion of the clinical testing, the design has been further evolved, and the developers are working with contract manufacturers to produce the final design and preparing for regulatory approval applications. PMID- 26356214 TI - The SIGN Nail: Factors in a Successful Device for Low-Resource Settings. AB - Surgeons in low-resource settings manage an increasing number of patients presenting with high-energy fractures. The number of surgeons and the operating time available are frequently not adequate to treat these fractures in a timely manner. A common cause of delay in treating fractures is waiting for the patient to accumulate sufficient funding to pay for the surgery, including the surgical implant. The donation of the SIGN intramedullary nail interlocking screw system obviates a major delay in timing of surgery. The SIGN intramedullary nail has been designed to be used in low-resource settings as it can be placed without fluoroscopy or electricity. The SIGN-trained surgeons are very skillful in hand reaming the canal, placing the nail, and interlocking screws without fluoroscopy. As more is learned about fracture healing, the SIGN system continues to evolve. The SIGN system is expanding to include deformity correction and soft tissue coverage. PMID- 26356216 TI - Notice of Duplicate Publication: Perceived benefits of pre-clinical simulation based training on clinical learning outcomes among Omani undergraduate nursing students. PMID- 26356215 TI - Lessons From the Boston Marathon Bombing: An Orthopaedic Perspective on Preparing for High-Volume Trauma in an Urban Academic Center. AB - The 2013 Boston Marathon bombing resulted in a mass casualty event that tested the limits of Boston-area trauma centers. The explosions, 12 seconds apart, led to the rapid influx of 124 patients with primarily lower extremity injuries in 5 different adult level 1 trauma centers. This study aimed to examine the existing hospital systems in place for disaster scenarios at the time of the event and identify areas for improvement. Preparation before the Boston Marathon bombing included coordinating the delivery of patients to area facilities and creating a framework for response at an institutional level. These simulations, coupled with the fact that the explosions occurred at a nexus of medical facilities, helped provide impactful care preventing any fatalities in patients who arrived at a Boston hospital that day. The experience at our institution led to the implementation of a more robust communication infrastructure and reinforced the value of preparatory drills. Within the Orthopaedic Surgery Department, we developed a more robust organizational hierarchy for mass casualty events and implemented a multitrauma follow-up clinic. We believe that it is the responsibility of every hospital to have systems in place to handle the rapid arrival of patients with multiple-trauma, and we hope that others can learn from our experience. PMID- 26356217 TI - Rethinking Colour Constancy. AB - Colour constancy needs to be reconsidered in light of the limits imposed by metamer mismatching. Metamer mismatching refers to the fact that two objects reflecting metameric light under one illumination may reflect non-metameric light under a second; so two objects appearing as having the same colour under one illuminant can appear as having different colours under a second. Yet since Helmholtz, object colour has generally been believed to remain relatively constant. The deviations from colour constancy registered in experiments are usually thought to be small enough that they do not contradict the notion of colour constancy. However, it is important to determine how the deviations from colour constancy relate to the limits metamer mismatching imposes on constancy. Hence, we calculated metamer mismatching's effect for the 20 Munsell papers and 8 pairs of illuminants employed in the colour constancy study by Logvinenko and Tokunaga and found it to be so extensive that the two notions-metamer mismatching and colour constancy-must be mutually exclusive. In particular, the notion of colour constancy leads to some paradoxical phenomena such as the possibility of 20 objects having the same colour under chromatic light dispersing into a hue circle of colours under neutral light. Thus, colour constancy refers to a phenomenon, which because of metamer mismatching, simply cannot exist. Moreover, it obscures the really important visual phenomenon; namely, the alteration of object colours induced by illumination change. We show that colour is not an independent, intrinsic attribute of an object, but rather an attribute of an object/light pair, and then define a concept of material colour in terms of equivalence classes of such object/light pairs. We suggest that studying the shift in material colour under a change in illuminant will be more fruitful than pursuing colour constancy's false premise that colour is an intrinsic attribute of an object. PMID- 26356219 TI - Correction: Self-Knowledge Dim-Out: Stress Impairs Metacognitive Accuracy. PMID- 26356218 TI - Increased Right Ventricular Fatty Acid Accumulation in Chronic Thromboembolic Pulmonary Hypertension. AB - RATIONALE: In right ventricular hypertrophy associated with severe pulmonary hypertension (PH), a shift of energy metabolism toward glycolysis occurs. There are few investigations regarding fatty acid metabolism in patients with PH and right ventricular hypertrophy. OBJECTIVES: To assess whether there is fatty acid accumulation in the hypertrophied right ventricle in patients with chronic thromboembolic pulmonary hypertension (CTEPH) and to determine whether this accumulation is related to hemodynamic variables obtained by right heart catheterization. METHODS: To assess fatty acid accumulation in the right ventricle, 123I-beta-methyl iodophenyl pentadecanoic acid (BMIPP) analog imaging was performed in control subjects (n=16) and patients with CTEPH (n=13) before (n=13) and after (n=8) pulmonary thromboendarterectomy. MEASUREMENTS AND MAIN RESULTS: There was increased 123I-BMIPP uptake in the right ventricle of subjects with CTEPH before pulmonary endarterectomy. Right ventricular 123I-BMIPP uptake decreased significantly after thromboendarterectomy (P=0.003) in parallel with the change of hemodynamic variables. The right ventricular BMIPP uptake was significantly correlated with the mean pulmonary artery pressure (r=0.51, P=0.0228) but not with pulmonary vascular resistance (r=0.39, P=0.0932). CONCLUSIONS: This is the first study that uses 123I-BMIPP uptake imaging to show that fatty acid accumulates in the right ventricle of patients with CTEPH and that the increased accumulation is reversible after pulmonary thromboendarterectomy. This study suggests that this imaging modality may be useful for monitoring right ventricle metabolic functions in severe PH. PMID- 26356220 TI - Biallelic and Genome Wide Association Mapping of Germanium Tolerant Loci in Rice (Oryza sativa L.). AB - Rice plants accumulate high concentrations of silicon. Silicon has been shown to be involved in plant growth, high yield, and mitigating biotic and abiotic stresses. However, it has been demonstrated that inorganic arsenic is taken up by rice through silicon transporters under anaerobic conditions, thus the ability to efficiently take up silicon may be considered either a positive or a negative trait in rice. Germanium is an analogue of silicon that produces brown lesions in shoots and leaves, and germanium toxicity has been used to identify mutants in silicon and arsenic transport. In this study, two different genetic mapping methods were performed to determine the loci involved in germanium sensitivity in rice. Genetic mapping in the biparental cross of Bala * Azucena (an F6 population) and a genome wide association (GWA) study with 350 accessions from the Rice Diversity Panel 1 were conducted using 15 MUM of germanic acid. This identified a number of germanium sensitive loci: some co-localised with previously identified quantitative trait loci (QTL) for tissue silicon or arsenic concentration, none co-localised with Lsi1 or Lsi6, while one single nucleotide polymorphism (SNP) was detected within 200 kb of Lsi2 (these are genes known to transport silicon, whose identity was discovered using germanium toxicity). However, examining candidate genes that are within the genomic region of the loci detected above reveals genes homologous to both Lsi1 and Lsi2, as well as a number of other candidate genes, which are discussed. PMID- 26356221 TI - The Unc-5 Receptor Is Directly Regulated by Tinman in the Developing Drosophila Dorsal Vessel. AB - During early heart morphogenesis cardiac cells migrate in two bilateral opposing rows, meet at the dorsal midline and fuse to form a hollow tube known as the primary heart field in vertebrates or dorsal vessel (DV) in Drosophila. Guidance receptors are thought to mediate this evolutionarily conserved process. A core of transcription factors from the NK2, GATA and T-box families are also believed to orchestrate this process in both vertebrates and invertebrates. Nevertheless, whether they accomplish their function, at least in part, through direct or indirect transcriptional regulation of guidance receptors is currently unknown. In our work, we demonstrate how Tinman (Tin), the Drosophila homolog of the Nkx 2.5 transcription factor, regulates the Unc-5 receptor during DV tube morphogenesis. We use genetics, expression analysis with single cell mRNA resolution and enhancer-reporter assays in vitro or in vivo to demonstrate that Tin is required for Unc-5 receptor expression specifically in cardioblasts. We show that Tin can bind to evolutionary conserved sites within an Unc-5 DV enhancer and that these sites are required for Tin-dependent transactivation both in vitro and in vivo. PMID- 26356223 TI - Positive enrichment of C-terminal peptides using oxazolone chemistry and biotinylation. AB - Selective capture of protein C-termini is still challenging in view of the lower reactivity of the carboxyl group relative to amino groups and difficulties in site-specifically labeling the carboxyl group on the C-terminus rather than that on the side chains of acidic amino acids. For highly efficient purification of C terminus peptides, a novel positive enrichment approach based on the oxazolone chemistry has been developed in this study. A bifunctional group reagent containing biotin and arginine was incorporated into the C-terminus of protein. Together with a streptavidin affinity strategy, the C-terminal peptides could be readily purified and analyzed by mass spectrometry (MS). Unlike the negative enrichment approach, C-terminal peptides, other than non-C-terminal peptides, were captured directly from the peptide mixture in this new method. The labeling efficiency (higher than 90%), enrichment selectivity (purifying C-terminal peptides from mixtures of non-C-terminal peptides at a 1:50 molar ratio), and ionization efficiencies in MS were dramatically improved. Moreover, the highly efficient identification of C-terminal peptides was further achieved by defining biotin as the 21st amino acid and optimizing the database search strategy. We have successfully identified 183 C-terminal peptides from Thermoanaerobacter tengcongensis using this creative method, which affords a highly selective and efficient purification approach for C-terminomics study. PMID- 26356222 TI - The Significance of the Prognostic Nutritional Index in Patients with Completely Resected Non-Small Cell Lung Cancer. AB - OBJECTIVES: Immunological parameters and nutritional status influence the outcome of patients with malignant tumors. A prognostic nutritional index, calculated using serum albumin levels and peripheral lymphocyte count, has been used to assess prognosis for various cancers. This study aimed to investigate whether this prognostic nutritional index affects overall survival and the incidence of postoperative complications in patients with completely resected non-small cell lung cancer. METHODS: We retrospectively reviewed the medical records of 409 patients with non-small cell lung cancer who underwent complete resection between 2005 and 2007 at the Aichi Cancer Center. RESULTS: The 5-year survival rates of patients with high (>=50) and low (<50) prognostic nutritional indices were 84.4% and 70.7%, respectively (p = 0.0011). Univariate analysis showed that gender, histology, pathological stage, smoking history, serum carcinoembryonic antigen levels, and prognostic nutritional index were significant prognostic factors. Multivariate analysis identified pathological stage and the prognostic nutritional index as independent prognostic factors. The frequency of postoperative complications tended to be higher in patients with a low prognostic nutritional index. CONCLUSIONS: The prognostic nutritional index is an independent prognostic factor for survival of patients with completely resected non-small cell lung cancer. PMID- 26356224 TI - [In Process Citation]. PMID- 26356225 TI - [In Process Citation]. PMID- 26356226 TI - [Social Security Needs Social Medicine: Self-image of Physicians Practicing Social Medicine in Statutory Health Insurances and Social Security Systems]. AB - OBJECTIVE: In January, 2014, the division "Social Medicine in Practice and Rehabilitation" of the German Society for Social Medicine and Prevention established a working group on the self-image of the physicians active in the field of social medicine (medical expertise and counseling). METHODS: The result of this work is the contribution presented here after consensus was achieved by specialists of social medicine from different fields and institutions (social security etc.) and in good cooperation with Prof. Dr. Gostomzyk and Prof. Dr. Robra. RESULTS: Based on the importance of an up to date social medicine for claimants and recipients of benefits on the one hand and the social security system on the other, and also on a description of the subjects, objectives and methods the following aspects are presented: . The perspective of social medicine. . Qualification in social medicine, concerning specialist training and continuing medical education. . The fields of duty of experts in social medicine. . The proceedings in social medicine. The working group identified challenges for the specialists in social medicine by a narrowed perception of social medicine by physicians in hospitals and practice, accompanied by an enlarged importance of expertise in social medicine, by the demand for more "patient orientation" and gain of transparency, and concerning the scientific foundation of social medicine. CONCLUSIONS: The working group postulates: . The perspective of social medicine should be spread more widely.. . Confidence in experts of social medicine and their independency should be strengthened.. . The not case-related consulting of the staff and executives should be expanded.. . Social medicine in practice needs support by politics and society, and especially by research and teaching.. . Good cooperation and transfer of experiences of the different branches of social security are essential for the impact of social medicine.. PMID- 26356227 TI - [Promotion of Young Scientists in Health Services Research - Evaluation of the Third Early Career Investigators Workshop in Health Services Research of the German Research Foundation (DFG)]. AB - The third Early Career Investigators Workshop in Health Services Research (NWA) of the German Research Foundation (DFG) was initiated and hosted in 2014 by the Centre for Health Services Research Cologne (ZVFK) in cooperation with the Centre for Health and Society (CHS) in Dusseldorf and the Interdisciplinary Centre for Healthcare Research (IZVF) in Witten. The aim of the NWA participation was submitting a research proposal to the DFG. Young scientists were invited to apply with a draft proposal. A total of 100 applications were received. Out of these, 20 participants (15 women and 5 men) were selected. The disciplines most frequently represented were medicine, psychology, and sociology. After a one-day preparatory workshop, the preparation and evaluation of a project proposal, a 5 day academy and finalization of the proposal, a total of 19 research proposals were submitted to the DFG, out of which 10 were approved. The funded projects will be presented in 2015 at the German Conference of Health Services Research (DKVF). PMID- 26356228 TI - [Strengthening Public and Global Health in Germany - an Appraisal of the Statement "Public Health in Germany" by the German Scientific Academies from June 16th 2015]. AB - In June 2015 the scientific academies "Leopoldina" and "acatech" and the union of the German academies of sciences and humanities published a statement on public and global health in Germany. The statement contains many valuable albeit generic and well-known recommendations. The few specific recommendations focus on centralizing research while weakening the role of universities and on the relative increase of research on public health genomics. These recommendations are not based on empirical or theoretical analyses and risk subverting successful developments of the recent past. To actually strengthen public and global health in Germany the existing institutions need to be backed up while designated funding of public and global health needs to be extended. PMID- 26356229 TI - The near-peer tutoring programme: embracing the 'doctors-to-teach' philosophy--a comparison of the effects of participation between the senior and junior near peer tutors. AB - BACKGROUND: While there is an increasing pool of literature documenting the benefits of near-peer tutoring programme, little is known about the benefits for junior and senior peer tutors. Knowledge of the peer tutors' perceived benefits at different levels of seniority will aid in the development of a near-peer tutoring programme that will better fulfil both curricula and personal aspirations of near-peer tutors. We, therefore, investigated the perceived benefits of participation in a near-peer tutoring programme for junior as well as senior near-peer tutors. METHODS: Pre- and post-participation questionnaires were distributed to near-peer tutors after their clinical skills teaching sessions with Phase I undergraduate medical students. The Peer Tutor Assessment Instrument questionnaires were distributed to the 1) students, and to the 2) near-peer tutors (junior and senior) after each teaching and learning session for self evaluation. RESULTS: The senior near-peer tutors felt that their participation in the programme had enhanced their skills (p=0.03). As a whole, the near-peer tutors were more motivated (Pre 5.32+/-0.46; Post 5.47+/-0.50; p=0.210) to participate in future teaching sessions but did not expect that having teaching experiences would make teaching as their major career path in the future (Pre 4.63+/-1.07; Post 4.54+/-0.98; p=0.701). The senior near-peer tutors were evaluated significantly higher by the students (p=0.0001). Students' evaluations of near-peer tutors on the domain of critical analysis was higher than self evaluations (p=0.003). CONCLUSIONS: Generally, the near-peer tutors perceived that they have benefited most in their skills enhancement and these near-peer tutors were scored highly by the students. However, senior near-peer tutors do not perceive that the programme has a lasting impact on their choice of career path. PMID- 26356230 TI - Temporal changes in tolerance of uncertainty among medical students: insights from an exploratory study. AB - BACKGROUND: Physicians' tolerance of uncertainty (TU) is a trait potentially associated with desirable outcomes, and emerging evidence suggests it may change over time. Past studies of TU, however, have been cross-sectional and have not measured tolerance of the different, specific types of uncertainty that physicians confront. We addressed these limitations in a longitudinal exploratory study of medical students. METHODS: At the end of medical school (Doctor of Medicine degree) Years 1 and 4, a cohort of 26 students at a US medical school completed measures assessing tolerance of different types of uncertainty: 1) complexity (uncertainty arising from features of information that make it difficult to comprehend); 2) risk (uncertainty arising from the indeterminacy of future outcomes); and 3) ambiguity (uncertainty arising from limitations in the reliability, credibility, or adequacy of information). Change in uncertainty specific TU was assessed using paired t-tests. RESULTS: Between Years 1 and 4, there was a significant decrease in tolerance of ambiguity (t=3.22, p=0.004), but no change in students' tolerance of complexity or risk. CONCLUSIONS: Tolerance of ambiguity--but not other types of uncertainty--decreases during medical school, suggesting that TU is a multidimensional, partially mutable state. Future studies should measure tolerance of different uncertainties and examine how TU might be improved. PMID- 26356231 TI - Biochemical Characterization of a Lanthanide-Dependent DNAzyme with Normal and Phosphorothioate-Modified Substrates. AB - A trivalent lanthanide (Ln(3+))-dependent RNA-cleaving DNAzyme, Ce13d, was recently isolated via in vitro selection. Ce13d is active in the presence of all Ln(3+) ions. Via introduction of a single phosphorothioate (PS) modification at the cleavage site, its activity with Ln(3+) decreases while all thiophilic metals can activate this DNAzyme. This property is unique to Ce13d and is not found in many other tested DNAzymes. This suggests the presence of a well-defined but general metal binding site. Herein, a systematic study of Ce13d with the PO substrate (using Ce(3+)) and the PS substrate (using Cd(2+)) is performed. In both the PO and PS systems, the highest activity was with ~10 MUM metal ions. Higher concentrations of Ce(3+) completely inhibit the activity, while Cd(2+) only slows the activity. A comparison of different metal ions suggests that the role of metal is to neutralize the phosphate negative charge. Both systems follow a similar pH-rate profile with a single deprotonation step, indicating similar reaction mechanisms. The activity difference between the Rp and Sp form of the PS substrate is <10-fold, which is much smaller than most known RNA-cleaving enzymes. Mutation studies identified eight highly conserved purines, among which the two adenines play mainly structural roles, while the guanines are likely to be involved in metal binding. Ce13d can serve as a model system for further understanding of DNAzyme biochemistry and bioinorganic chemistry. PMID- 26356232 TI - Reorientation of Isomeric Butanols: The Multiple Effects of Steric Bulk Arrangement on Hydrogen-Bond Dynamics. AB - Molecular dynamics simulations are used to investigate OH reorientation in the four isomeric butanols in their bulk liquid state to examine the influence of the arrangement of the steric bulk on the alcohol reorientational and hydrogen-bond (H-bond) dynamics. The results are interpreted within the extended jump model in which the OH reorientation is decomposed into contributions due to "jumps" between H-bond partners and "frame" reorientation of the intact H-bonded pair. Reorientation is fastest in iso-butanol and slowest in tert-butanol, while sec- and n-butanol have similar reorientation times. This latter result is a fortuitous cancellation between the jump and frame reorientation in the two alcohols. The extended jump model is shown to provide a quantitative description of the OH reorientation times. A detailed analysis of the jump times shows that a combination of entropic, enthalpic, and dynamical factors, including transition state recrossing effects, all play a role. A simple model based on the liquid structure is proposed to estimate the energetic and entropic contributions to the jump time. This represents the groundwork for a predictive model of OH reorientation in alcohols, but additional studies are required to better understand the frame reorientation and transition state recrossing effects. PMID- 26356233 TI - Current density imaging sequence for monitoring current distribution during delivery of electric pulses in irreversible electroporation. AB - BACKGROUND: Electroporation is gaining its importance in everyday clinical practice of cancer treatment. For its success it is extremely important that coverage of the target tissue, i.e. treated tumor, with electric field is within the specified range. Therefore, an efficient tool for the electric field monitoring in the tumor during delivery of electroporation pulses is needed. The electric field can be reconstructed by the magnetic resonance electric impedance tomography method from current density distribution data. In this study, the use of current density imaging with MRI for monitoring current density distribution during delivery of irreversible electroporation pulses was demonstrated. METHODS: Using a modified single-shot RARE sequence, where four 3000 V and 100 MUs long pulses were included at the start, current distribution between a pair of electrodes inserted in a liver tissue sample was imaged. Two repetitions of the sequence with phases of refocusing radiofrequency pulses 90 degrees apart were needed to acquire one current density image. For each sample in total 45 current density images were acquired to follow a standard protocol for irreversible electroporation where 90 electric pulses are delivered at 1 Hz. RESULTS: Acquired current density images showed that the current density in the middle of the sample increased from first to last electric pulses by 60%, i.e. from 8 kA/m2 to 13 kA/m2 and that direction of the current path did not change with repeated electric pulses significantly. CONCLUSIONS: The presented single-shot RARE-based current density imaging sequence was used successfully to image current distribution during delivery of short high-voltage electric pulses. The method has a potential to enable monitoring of tumor coverage by electric field during irreversible electroporation tissue ablation. PMID- 26356234 TI - Native and Non-Native Supergeneralist Bee Species Have Different Effects on Plant Bee Networks. AB - Supergeneralists, defined as species that interact with multiple groups of species in ecological networks, can act as important connectors of otherwise disconnected species subsets. In Brazil, there are two supergeneralist bees: the honeybee Apis mellifera, a non-native species, and Trigona spinipes, a native stingless bee. We compared the role of both species and the effect of geographic and local factors on networks by addressing three questions: 1) Do both species have similar abundance and interaction patterns (degree and strength) in plant bee networks? 2) Are both species equally influential to the network structure (nestedness, connectance, and plant and bee niche overlap)? 3) How are these species affected by geographic (altitude, temperature, precipitation) and local (natural vs. disturbed habitat) factors? We analyzed 21 plant-bee weighted interaction networks, encompassing most of the main biomes in Brazil. We found no significant difference between both species in abundance, in the number of plant species with which each bee species interacts (degree), and in the sum of their dependencies (strength). Structural equation models revealed the effect of A. mellifera and T. spinipes, respectively, on the interaction network pattern (nestedness) and in the similarity in bee's interactive partners (bee niche overlap). It is most likely that the recent invasion of A. mellifera resulted in its rapid settlement inside the core of species that retain the largest number of interactions, resulting in a strong influence on nestedness. However, the long term interaction between native T. spinipes and other bees most likely has a more direct effect on their interactive behavior. Moreover, temperature negatively affected A. mellifera bees, whereas disturbed habitats positively affected T. spinipes. Conversely, precipitation showed no effect. Being positively (T. spinipes) or indifferently (A. mellifera) affected by disturbed habitats makes these species prone to pollinate plant species in these areas, which are potentially poor in pollinators. PMID- 26356235 TI - Relationship between Serum Uric Acid Levels and Chronic Kidney Disease in a Japanese Cohort with Normal or Mildly Reduced Kidney Function. AB - BACKGROUND: Some observational studies have shown the relationships between hyperuricemia and chronic kidney disease (CKD); however, the threshold of serum uric acid (SUA) for deterioration of kidney function and the association between SUA and kidney injury by baseline kidney function remains unclear. This study aimed to clarify the relationships between SUA and reduced kidney function. METHODS: We analyzed a historical cohort of male Japanese individuals who underwent medical checkup between 1998 and 2007. Participants with baseline data and who were followed up for at least one year were included and stratified according to baseline kidney function. Kidney function was classified as normal [estimated glomerular filtration rate (eGFR) >= 90 ml/min/1.73 m2] or mildly reduced (eGFR 60-89 ml/min/1.73 m2). The outcome measured was kidney impairment defined as a decrease in eGFR to < 60 ml/min/1.73 m2. Associations between SUA and risk for outcome and eGFR slopes were assessed. RESULTS: A total of 41632 subjects with mean age 45.4 years were included. During a mean follow-up of four years, 3186 (7.6%) subjects developed kidney dysfunction. Subjects with SUA >= 6.0 mg/dL had a significantly increased risk for kidney impairment compared with subjects with SUA of 4-4.9 mg/dL. SUA threshold levels were different according to baseline kidney function; SUA >= 7.0 and >= 6.0 mg/dL for normal and mildly reduced kidney function, respectively. Approximately the same trends were observed for eGFR slopes. CONCLUSION: In the general population, hyperuricemia appears to be a risk factor for kidney impairment in males. For participants with mild kidney dysfunction, even a slight elevation of SUA can be a risk factor. PMID- 26356236 TI - Pelvic lymph node dissection for nodal oligometastatic prostate cancer detected by 68Ga-PSMA-positron emission tomography/computerized tomography. AB - BACKGROUND: The first evaluation of pelvic extended lymph node dissection (pLND) in oligometastatic prostate cancer (PCa) detected by (68)Ga-PSMA PET/CT. METHODS: Retrospective analysis of 35 PCa patients underwent (68)Ga-PSMA PET/CT affected by biochemical recurrence (BCR) after curative treatment (n = 23) or before primary therapy of high-risk PCa (n = 12). We performed pLND associated with pathologic imaging in 17 men with nodal oligometastatic PCa. RESULTS: Indicative lesions for PCa in PET/CT were detected in 91.4% (32 of 35) of patients. Nodal, bone, visceral (pulmonary), and within the prostate suspected disease were detected in 72% (23 of 32), 16% (5 of 32), 6% (2 of 32), and 47% (15 of 32) of patients, respectively. Median serum PSA in patients with pathological radiotracer uptake in recurrent and high-risk PCa patients was 2.9 ng/ml (range 0.18-30) and 19.5 ng/ml (range 6-90), respectively. The median number of removed lymph nodes with pLND in recurrent and high-risk PCa was 10 (range 4-17) and 12 (range 8-29) per patient and the median number of positive lymph nodes was 1 (range 1-2) and 3 (2-3) per patient, respectively. In total, two false positive and one false-negative lymph node were found. Diagnostic accuracies per nodal lesion in total of 213 removed nodes: sensitivity, 94%; specificity, 99%; positive predictive value (PPV), 89%, and negative predictive value (NPV), 99.5%. After pLND, 53% (9 of 17) of patients received androgen deprivation therapy and/or radiation therapy and hormonal therapy, while 47% (8 of 17) of patients remained free of any post-surgery therapy. Follow-up PSA remained less than 0.2 ng/ml in 82% (14 of 17) of patients. After pLND, immediate BCR (PSA never measured less than 0.2 ng/ml) in 18% (3 of 17) of patients was recorded. CONCLUSIONS: This represents the first study of pLND in the setting of nodal oligometastatic PCa detected by (68)Ga-PSMA PET/CT. The use of (68)Ga-PSMA PET/CT could be to improve the accuracy for the detection of nodal micrometastases. These promising findings need validation in larger studies. PMID- 26356237 TI - Removing noises caused by motion artefacts in microcirculation maps of human skin in vivo. AB - This paper presents a zero-padding and cross-correlation technique-based correlation mapping optical coherence tomography (ZPCC-cmOCT) to reconstruct microcirculation maps of human skin in vivo, which can remove the background decorrelation noise caused by motion artefacts. In conventional correlation mapping optical coherence tomography method, the correlation degree of static tissue may be lowered by the motion artefacts due to cardiac and respiratory motion, resulting in background decorrelation noise in microcirculation maps. In zero-padding and cross-correlation technique-based correlation mapping optical coherence tomography method, structural images are first obtained by performing Fourier transform on zero-padded interference fringes, and then cross-correlation based image registration is utilized to align local areas in two adjacent structural images. Finally, correlation mapping optical coherence tomography method is performed to generate microcirculation maps. Both phantom experiments and in vivo experiments were implemented and the results demonstrate that the proposed method is capable of providing microcirculation maps with the background decorrelation noise removed. PMID- 26356238 TI - Secondary Structural Elements of the HCV X-region Involved in Viral Replication. AB - BACKGROUND AND AIMS: The noncoding regions in the 3'-untranslated region (UTR) of the hepatitis C virus (HCV) genome contain secondary structures that are important for replication. The aim of this study was to identify detailed conformational elements of the X-region involved in HCV replication. METHODS: Ribonucleic acid (RNA) structural analogs X94, X12, and X12c were constructed to have identical conformation but 94%, 12%, and 0% sequence identity, respectively, to the X region of HCV genotype 2a. Effects of structural analogs on replication of HCV genotypes 1b and 2a HCV RNA were studied by quantitative reverse transcriptase polymerase chain reaction. RESULTS: In replicon BB7 cells, a constitutive replication model, HCV RNA levels decreased to 55%, 52%, 53%, and 54% after transfection with expression plasmids generating RNA structural analogs 5B-46, X-94, X-12, and X-12c, respectively (p<0.001 for all). In an HCV genotype 2a infection model, RNA analogs 5B-46, X-94, and X-12 in hepatic cells inhibited replication to 11%, 9%, and 12%, respectively. Because the X-12 analog was only 12% identical to the corresponding sequence of HCV genotype 2a, the sequence per se, or antisense effects were unlikely to be involved. CONCLUSIONS: The data suggest that conformation of secondary structures in 3'-UTR of HCV RNA genome is required for HCV replication. Stable expression of RNA analogs predicted to have identical stem-loop structures might inhibit HCV infection of hepatocytes in liver and may represent a novel approach to design anti-HCV agents. PMID- 26356239 TI - Molecular Structural Design of Conjugated Microporous Poly(Benzooxadiazole) Networks for Enhanced Photocatalytic Activity with Visible Light. AB - A simple structural design principle and band position alignment of conjugated microporous polymers for enhanced photocatalytic efficiency is presented. The valence and conduction band positions of the polymer networks can be fine-tuned by altering the substitution positions on the centered phenyl unit to match the required redox potential of the catalytic reactions under visible light. PMID- 26356240 TI - Quality of Life in Patients With Chronic Rhinosinusitis and Sleep Dysfunction Undergoing Endoscopic Sinus Surgery: A Pilot Investigation of Comorbid Obstructive Sleep Apnea. AB - IMPORTANCE: Patients with chronic rhinosinusitis (CRS) have reduced sleep quality linked to their overall well-being and disease-specific quality of life (QOL). Other primary sleep disorders also affect QOL. OBJECTIVE: To determine the impact of comorbid obstructive sleep apnea (OSA) on CRS disease-specific QOL and sleep dysfunction in patients with CRS following functional endoscopic sinus surgery. DESIGN, SETTING, AND PARTICIPANTS: Prospective multisite cohort study conducted between October 2011 and November 2014 at academic, tertiary referral centers with a population-based sample of 405 adults. INTERVENTION: Functional endoscopic sinus surgery for medically refractory symptoms of CRS. MAIN OUTCOMES AND MEASURES: Primary outcome measures consisted of preoperative and postoperative scores operationalized by the Rhinosinusitis Disability Index (RSDI) survey, the 22-item Sinonasal Outcome Test (SNOT-22), and the Pittsburgh Sleep Quality Index (PSQI). Obstructive sleep apnea was the primary, independent risk factor. RESULTS: Of 405 participants, 60 (15%) had comorbid OSA. A total of 285 (70%) participants provided preoperative and postoperative survey responses, with a mean (SD) of 13.7 (5.3) months of follow-up. Significant postoperative improvement (P < .05) was reported across all mean disease-specific QOL measures for both participants with and without comorbid OSA. Participants without OSA reported significant greater improvement in unadjusted mean (SD) RSDI global scores (-25.0 [23.3] vs. -16.5 [22.1]; P = .03), RSDI physical (-10.7 [9.2] vs. 7.3 [9.1]; P = .03) and functional (-8.4 [8.7] vs. -5.1 [7.5]; P = .03) subdomain scores, and SNOT-22 rhinologic symptom domain scores (-9.1 [7.7] vs. -5.7 [6.9]; P = .008). Participants without OSA also reported greater improvements on mean (SD) PSQI global (-1.9 [4.0] vs. -0.5 [3.7]; P = .03), sleep quality (-0.4 [0.8] vs. -0.03 [0.7]; P = .02), and sleep disturbance (-0.4 [0.7] vs. -0.1 [0.7]; P = .03) scores. The majority of these associations were found to be durable after adjustment for alternate independent cofactors using stepwise linear regression modeling. CONCLUSIONS AND RELEVANCE: Patients with CRS and comorbid OSA have poor QOL with substantial disease-specific QOL improvements following surgery. Patients who present with CRS should be assessed for primary sleep disorders and, if identified, should be treated concurrently for both CRS and OSA to improve sleep dysfunction to optimize surgical outcomes. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01332136. PMID- 26356242 TI - Use of Management Pathways or Algorithms in Children With Chronic Cough: Systematic Reviews. AB - BACKGROUND: Use of appropriate cough pathways or algorithms may reduce the morbidity of chronic cough, lead to earlier diagnosis of chronic underlying illness, and reduce unnecessary costs and medications. We undertook three systematic reviews to examine three related key questions (KQ): In children aged ?14 years with chronic cough (> 4 weeks' duration), KQ1, do cough management protocols (or algorithms) improve clinical outcomes? KQ2, should the cough management or testing algorithm differ depending on the duration and/or severity? KQ3, should the cough management or testing algorithm differ depending on the associated characteristics of the cough and clinical history? METHODS: We used the CHEST expert cough panel's protocol. Two authors screened searches and selected and extracted data. Only systematic reviews, randomized controlled trials (RCTs), and cohort studies published in English were included. RESULTS: Data were presented in Preferred Reporting Items for Systematic Reviews and Meta analyses flowcharts and summary tabulated. Nine studies were included in KQ1 (RCT = 1; cohort studies = 7) and eight in KQ3 (RCT = 2; cohort = 6), but none in KQ2. CONCLUSIONS: There is high-quality evidence that in children aged ?14 years with chronic cough (> 4 weeks' duration), the use of cough management protocols (or algorithms) improves clinical outcomes and cough management or the testing algorithm should differ depending on the associated characteristics of the cough and clinical history. It remains uncertain whether the management or testing algorithm should depend on the duration or severity of chronic cough. Pending new data, chronic cough in children should be defined as > 4 weeks' duration and children should be systematically evaluated with treatment targeted to the underlying cause irrespective of the cough severity. PMID- 26356243 TI - Cell-free protein synthesis enables high yielding synthesis of an active multicopper oxidase. AB - Multicopper oxidases (MCOs) are broadly distributed in all kingdoms of life and perform a variety of important oxidative reactions. These enzymes have potential biotechnological applications; however, the applications are impeded by low expression yields in traditional recombinant hosts, solubility issues, and poor copper cofactor assembly. As an alternative to traditional recombinant protein expression, we show the ability to use cell-free protein synthesis (CFPS) to produce complex MCO proteins with high soluble titers. Specifically, we report the production of MCOs in an Escherichia coli-based cell-free transcription translation system. Total yields as high as 1.2 mg mL(-1) were observed after a 20-h batch reaction. More than 95% of the protein was soluble and activity was obtained by simple post-CFPS addition of copper ions in the form of CuSO4 . Scale up reactions were achieved from 15 to 100 uL without a decrease in productivity and solubility. CFPS titers were higher than in vivo expression titers and more soluble, avoiding the formation of inclusion bodies. Our work extends the utility of the cell-free platform to the production of active proteins containing copper cofactors and demonstrates a simple method for producing MCOs. PMID- 26356245 TI - A physiologically based pharmacokinetic modeling approach to predict drug-drug interactions between domperidone and inhibitors of CYP3A4. AB - Domperidone is a dopamine receptor antagonist and a substrate of CYP3A4, hence there is a potential for CYP3A inhibition-based drug-drug interactions (DDI). A physiologically based pharmacokinetic model was developed to describe DDIs between domperidone and three different inhibitors of CYP3A4. Simcyp V13.1 was used to simulate human domperidone pharmacokinetics and DDIs. Inputs included domperidone chemical and physical properties (LogP, pKa, etc.), in vitro human liver microsomal data and pharmacokinetic parameters from single-dose intravenous clinical studies in healthy participants. The simulated mean maximum domperidone plasma concentration and AUC after single- and multiple-oral doses under diverse conditions were within 1.1-1.4 fold of the observed values. The simulated intestinal availability, hepatic availability and the fraction absorbed were 0.45 +/- 0.14, 0.31 +/- 0.10 and 0.89 +/- 0.11, respectively, and comparable to observed in vivo values. The simulated ratios of AUC and C(max) in the presence of ketoconazole, erythromycin or itraconazole to baseline were consistent with the observed ratios. Simulated ketoconazole, erythromycin, itraconazole and C(max,ss) and AUC(ss) were within 1.5-fold of the observed values. PMID- 26356244 TI - How to perform transcaval access and closure for transcatheter aortic valve implantation. AB - Transcaval, or caval-aortic, access is a promising approach for fully percutaneous transcatheter aortic valve implantation in patients without good conventional access options. This tutorial review provides step-by-step guidance to planning and executing the procedure, along with approaches to remedy complications. PMID- 26356247 TI - Adult weight gain and risk of prostate cancer: A dose-response meta-analysis of observational studies. AB - The association between adult weight gain and risk of prostate cancer has not been widely studied and the findings are inconsistent. Therefore, our study aimed to investigate the association between adult weight gain and risk of prostate cancer. PubMed, Embase and Web of Science databases were searched for relevant studies published before September 2014 using terms related to weight gain and prostate cancer. Summary estimates were obtained using the random-effects model. Dose-response meta-analysis, sensitivity analysis and publication bias tests were performed. Nine studies involving 497,634 participants and 22,338 cancer cases were included. For total prostate cancer, a positive relationship with adult weight gain was observed until weight gain increased to >30 kg. For low intermediate-risk prostate cancer, a positive relationship with adult weight gain was observed until weight gain increased to >15 kg. For high-risk prostate cancer, we observed a positive linear relationship with adult weight gain with a relative risk (RR) of 1.02 [95% confidence interval (CI) 1.00-1.04] for every 5 kg increase. For fatal prostate cancer, we observed a positive linear relationship with adult weight gain with an RR of 1.12 (95% CI: 1.05-1.19) for every 5-kg increase. There is evidence that adult weight gain is associated with an increased risk of high-risk and fatal prostate cancer, but only low weight gain is positively associated with low-intermediate-risk prostate cancer. PMID- 26356248 TI - An evaluation of training for lay providers in the use of Motivational Interviewing to promote academic achievement among urban youth. AB - This study examined training outcomes for lay service providers who participated in a Motivational Interviewing (MI) training program designed to help increase intrinsic motivation and academic achievement among urban low-income and minority youth. Seventeen lay academic advisors received 16 hours of training in MI. Two, two-hour booster sessions plus five, two- hour weekly group supervision sessions were conducted with lay advisors over a period of seven months. One-hundred percent of lay advisors (n =17) participated in all training, booster sessions and assessments. Seventy-one percent of lay advisors (n=12) completed all group supervision sessions and submitted tapes for review. MI training was associated with increased knowledge of MI principles among lay service providers; increased proficiency in responding to simulated clients in an MI consistent style; increased use of MI adherent behaviors in sessions with real clients and maintenance of high motivation to use MI from pretest to posttest. Although lay advisors increased their knowledge of MI, further training is required for advisors to increase competence in delivering MI. Overall, Implications for using MI in the context of school-based settings is discussed. PMID- 26356249 TI - Benzodiazepine use in COPD: empirical evidence from Norway. AB - BACKGROUND: The common comorbidities associated with COPD include, among others, anxiety, depression, and insomnia, for which the typical treatment involves the use of benzodiazepines (BZD). However, these medicines should be used with extra caution among COPD patients, since treatment with traditional BZD may compromise respiratory function. AIMS: This study investigated the use of BZD among persons suffering from COPD by analyzing three relevant indicators: 1) the sum of defined daily doses (DDD); 2) the number of prescribers involved; and 3) the number of different types of BZD used. DATA AND METHODS: The study builds on a linkage of national prescription data and patient-administrative data, which includes all Norwegian drug prescriptions to persons hospitalized with a COPD diagnosis during 2009, amounting to a total of 5,380 observations. Regression techniques were used to identify the patients and the clinical characteristics associated with BZD use. RESULTS: Of the 5,380 COPD patients treated in hospital during 2009, 3,707 (69%) were dispensed BZD during the following 12 months. Moreover, they were dispensed on average 197.08 DDD, had 1.22 prescribers, and used 0.98 types of BZD during the year. Women are more likely to use BZD for all levels of BZD use. Overnight planned care not only increases the risk of BZD use (DDD), but also the number of prescribers and the types of BZD in use. CONCLUSION: In light of the high levels of BZD prescription found in this study, especially among women, it is recommended that general practitioners, hospital specialists, and others treating COPD patients should aim to acquire a complete picture of their patients' BZD medication before more is prescribed in order to keep the use to a minimum. PMID- 26356250 TI - Molecular species delimitation methods recover most song-delimited cicada species in the European Cicadetta montana complex. AB - Molecular species delimitation is increasingly being used to discover and illuminate species level diversity, and a number of methods have been developed. Here, we compare the ability of two molecular species delimitation methods to recover song-delimited species in the Cicadetta montana cryptic species complex throughout Europe. Recent bioacoustics studies of male calling songs (premating reproductive barriers) have revealed cryptic species diversity in this complex. Maximum likelihood and Bayesian phylogenetic analyses were used to analyse the mitochondrial genes COI and COII and the nuclear genes EF1alpha and period for thirteen European Cicadetta species as well as the closely related monotypic genus Euboeana. Two molecular species delimitation methods, general mixed Yule coalescent (GMYC) and Bayesian phylogenetics and phylogeography, identified the majority of song-delimited species and were largely congruent with each other. None of the molecular delimitation methods were able to fully recover a recent radiation of four Greek species. PMID- 26356251 TI - Cell-penetrating compounds preferentially bind glycosaminoglycans over plasma membrane lipids in a charge density- and stereochemistry-dependent manner. AB - Cell-penetrating compounds (CPCs) are often conjugated to drugs and genes to facilitate cellular uptake. We hypothesize that the electrostatic interaction between the positively charged amines of the cell-penetrating compounds and the negatively charged glycosaminoglycans (GAGs) extending from cell surfaces is the initiating step in the internalization process. The interactions of generation 5 PAMAM dendrimer, Tat peptide and 25 kDa linear PEI with four different GAGs have been studied using isothermal titration calorimetry to elucidate structure function relationships that could lead to improved drug and gene delivery methods to a wide variety of cell types. Detailed thermodynamic analysis has determined that CPC-GAG binding constants range from 8.7*10(3) to 2.4*10(6)M(-1) and that affinity is dependent upon GAG charge density and stereochemistry and CPC molecular weight. The effect of GAG composition on affinity is likely due to hydrogen bonding between CPC amines and amides and GAG hydroxyl and amine groups. These results were compared to the association of CPCs with lipid vesicles of varying composition as model plasma membranes to finally clarify the relative importance of each cell surface component in initial cell recognition. CPC-lipid affinity increases with anionic lipid content, but GAG affinity is higher for all cell-penetrating compounds, confirming the role these heterogeneous polysaccharides play in cellular association and clustering. PMID- 26356252 TI - Are pregnant women safer in motor vehicle accidents? AB - OBJECTIVE: Motor vehicle accidents (MVAs) are a major incidental cause of pregnancy-associated maternal deaths in the US. The goal of this research was to evaluate the incidence, risks, and fetal and maternal outcomes of pregnant women involved in MVAs. In addition, we examined the relationship between the injury severity score (ISS) and car seat location in pregnant and non-pregnant women. METHODS: This involved a retrospective cohort study of female patients who were involved in MVAs and hospitalized between the years 2006 and 2013. Data were collected from the Israeli National Trauma Registry. Severity and outcomes of pregnant and non-pregnant women with blunt trauma were compared. RESULTS: In this study, 3794 pregnant and 3441 non-pregnant patients aged 18-40 years were analyzed. The majority of pregnant patients were drivers (n=2515, 67%) as opposed to passengers (n=1279, 33%). Pregnant patients had lower ISS than non-pregnant patients (P<0.001). Out of these pregnant patients, 38 (1%) had adverse maternal fetal pregnancy outcomes, including (1) placental abruption 0.1% and (2) miscarriage (0.2%). One pregnant patient died (0.03%) compared with 32 (0.93%) of the non-pregnant patients (P<0.0001). A significant negative correlation between gestational age and spontaneous abortion was found (P<0.009). CONCLUSIONS: The severity of injury and the mortality rate of pregnant patients involved in MVAs are significantly lower compared with non-pregnant patients. Pregnant drivers had a significantly lower severity of trauma compared with pregnant passengers. PMID- 26356253 TI - OpenGrowth: An Automated and Rational Algorithm for Finding New Protein Ligands. AB - We present a new open-source software, called OpenGrowth, which aims to create de novo ligands by connecting small organic fragments in the active site of proteins. Molecule growth is biased to produce structures that statistically resemble drugs in an input training database. Consequently, the produced molecules have superior synthetic accessibility and pharmacokinetic properties compared with randomly grown molecules. The growth process can take into account the flexibility of the target protein and can be started from a seed to mimic R group strategy or fragment-based drug discovery. Primary applications of the software on the HIV-1 protease allowed us to quickly identify new inhibitors with a predicted Kd as low as 18 nM. We also present a graphical user interface that allows a user to select easily the fragments to include in the growth process. OpenGrowth is released under the GNU GPL license and is available free of charge on the authors' website and at http://opengrowth.sourceforge.net/ . PMID- 26356254 TI - The Beneficial Effect of Parasympathetic Reactivation on Sympathetic Drive During Simulated Rugby Sevens. AB - PURPOSE: To determine whether a facilitated recovery via cold-water immersion (CWI) after simulated rugby sevens would influence parasympathetic reactivation and repeated-sprint (RS) performance across 6 matches in a 2-d tournament. METHODS: Ten male team-sport athletes completed 6 rugby sevens match simulations over 2 d with either postmatch passive recovery (PAS) or CWI in a randomized crossover design. Parasympathetic reactivation was determined via the natural logarithm of the square root of the mean of the sum of the squares of differences between adjacent R-R intervals (ln rMSSD). RS performance was calculated as time taken (s) to complete 6 * 30-m sprints within the first half of each match. RESULTS: There were large increases in postintervention ln rMSSD between CWI and PAS after all matches (ES 90% CL: +1.13; +/-0.21). Average heart rate (HR) during the RS performance task (HRAverage RS) was impaired from baseline from match 3 onward for both conditions. However, HRAverage RS was higher with CWI than with PAS (ES 90% CL: 0.58; +/-0.58). Peak HR during the RS performance task (HRPeak RS) was similarly impaired from baseline for match 3 onward during PAS and for match 4 onward with CWI. HRPeak RS was very likely higher with CWI than with PAS (ES 90% CL: +0.80; +/-0.56). No effects of match or condition were observed for RS performance, although there were moderate correlations between the changes in HRAverage RS (r 90% CL: -0.33; +/-0.14), HRPeak RS (r 90% CL: -0.38; +/-0.13), and RS performance. CONCLUSION: CWI facilitated cardiac parasympathetic reactivation after a simulated rugby sevens match. The decline in average and peak HR across matches was partially attenuated by CWI. This decline was moderately correlated with a reduction in RS performance. PMID- 26356255 TI - The effect of six weeks of sling exercise training on trunk muscular strength and endurance for clients with low back pain. AB - [Purpose] The purpose of this study was to investigate the effects of 6 weeks sling exercise training for clients with low back pain on the levels of pain, disability, muscular strength and endurance. [Subjects and Methods] Twelve chronic LBP subjects participated in this study. Subjects were randomly divided into a control group and a training group. Subjects in the training group performed sling exercise training for six weeks, and participants in the control group did not perform any exercise. [Results] Pain, disability levels and muscular strength significantly improved in the training group, but not in the control group. The left multifidus showed a significant improvement in muscular endurance, measured as the slope of the median frequency after training. [Conclusion] Six weeks of sling exercise training was effective at reducing pain intensity, and improving the disability level and trunk muscular strength of subjects with low back pain. PMID- 26356256 TI - A biomechanical model for cell polarization and intercalation during Drosophila germband extension. AB - Germband extension during Drosophila development features the merging of cells along the dorsal-ventral (DV) axis and their separation along the anterior posterior (AP) axis. This intercalation process involves planar cell polarity, anisotropic contractile forces along cell edges, and concerted cell deformation and movement. Although prior experiments have probed each of these factors separately, the connection among them remains unclear. This paper presents a chemo-mechanical model that integrates the three factors into a coherent framework. The model predicts the polarization of Rho-kinase, myosin and Bazooka downstream of an anisotropic Shroom distribution. In particular, myosin accumulates on cell edges along the DV axis, causing them to contract into a vertex. Subsequently, medial myosin in the cells anterior and posterior to the vertex helps to elongate it into a new edge parallel to the body axis. Thus, the tissue extends along the AP axis and narrows in the transverse direction through neighbor exchange. Model predictions of the polarity of the proteins and cell and tissue deformation are in good agreement with experimental observations. PMID- 26356257 TI - In the midst of the antimicrobial discovery conundrum: an overview. PMID- 26356258 TI - Translational deficiencies in antibacterial discovery and new screening paradigms. AB - An impending disaster is currently developing in the infectious disease community: the combination of rapidly emerging multidrug-resistance among clinically relevant bacterial pathogens, together with an unprecedented withdrawal from industrial dedication to this disease area, is jeopardizing human health on a societal level. For those who remain focused and dedicated to identifying solutions to this growing problem, additional challenges await when in vitro activity does not correlate with in vivo efficacy. Thus the development of more effective translational assays will greatly improve and streamline the process of identifying novel antibacterial agents that can stand the test of preclinical and clinical development. Here we describe recent examples of research that justify the need for such assays. PMID- 26356259 TI - Applications of imaging for bacterial systems biology. AB - Imaging has fueled exciting advances in bacterial cell biology, which have led to exquisite understanding of mechanisms of protein localization and cell growth in select cases. Nonetheless, it remains a challenge to connect subcellular dynamics to cellular phenotypes. In this review, I explore synergies between imaging and systems approaches to bacterial physiology. I highlight how single-cell, time lapse imaging under environmental or chemical perturbations yields insights that complement traditional observations based on population-level growth on long time scales. Next, I discuss applications of high-throughput fluorescence imaging to dissect genetic pathways and drug targets. Finally, I describe how confocal imaging is illuminating the role of spatial organization in the structure and function of bacterial communities, from biofilms to the intestinal microbiota. PMID- 26356260 TI - HULC and Linc00152 Act as Novel Biomarkers in Predicting Diagnosis of Hepatocellular Carcinoma. AB - BACKGROUND/AIMS: The alterations of long non-coding RNAs (lncRNAs) are related to multiple diseases. They can be detected in plasma as biomarkers for the diagnosis of multiple diseases. In this study, we aimed to determine the expression of circulating lncRNAs in human, which may be promising biomarkers for the diagnosis of hepatocellular carcinoma (HCC). METHODS: Eight lncRNAs were chosen as candidates on the basis of the literature to evaluate the diagnostic value and accuracy of the plasma lncRNA profiling system. The candidate lncRNAs were validated by qRT-PCR arranged in the training and validation sets. Additional double-blind testing was performed in 20 patients clinically suspected of having HCC. RESULTS: Circulating HULC and Linc00152 were significantly up-regulated in plasma samples of HCC patients during training set and validation set. Areas under the receiver operating characteristic (ROC) curves of the validated two lncRNAs signature were 0.78 and 0.85, respectively. Combination of HULC and Linc00152 possessed a moderate ability to discrimination between HCC and control with an area under ROC value of 0.87 while the combination of AFP was 0.89 with a positive correlation with tissues expression. CONCLUSIONS: Our results suggest that both plasma levels of HULC and Linc00152 achieve a fine diagnostic accuracy in diagnosing ontogenesis and metastasis of HCC and may act as novel biomarkers for HCC. PMID- 26356261 TI - Autophagy Plays a Protective Role in Advanced Glycation End Product-Induced Apoptosis in Cardiomyocytes. AB - BACKGROUND/AIMS: To investigate the effect of advanced glycation endproduct induced autophagy in rat cardiomyocytes and to identify the role of autophagy in advanced glycation end product-induced cell apoptosis. METHODS: After cultured rat cardiomyocytes were treated with advanced glycation end products (AGEs), protein expression was detected by western blotting, autophagosomes were observed by electron microscopy, the cell apoptotic rate was determined by flow cytometry, and cell variability was quantified by the MTT assay. RESULTS: After cultured cardiomyocytes were treated with AGEs, the level of autophagy-associated protein LC3-II was up-regulated and SQSTM1/p62 was down-regulated; the number of autophagosomes was increased. Compared with the control group, the apoptotic rate of cardiomyocytes increased, and the cardiomyocyte viability was decreased in the AGE-treated group. Furthermore, pretreating cells with3-MA, an autophagy inhibitor, could enhance these effects. Treatment with AGEs activated phospho ERK, phospho-JNK, and phospho-p38/MAPK but inhibited phospho-Akt and phospho mTOR. Pretreatment with an ERK inhibitor and an Akt activator could inhibit AGE induced autophagy, demonstrating that AGEs induce autophagy in cardiomyocytes through the ERK and Akt signalling pathways. CONCLUSION: AGEs can induce autophagy through the PI3K/AKT/mTOR and ERK signalling pathways and induce apoptosis through the PI3K/AKT/mTOR and p38/MAPK signalling pathways in rat cardiomyocytes. Autophagy plays a protective role in AGE-induced apoptosis in cardiomyocytes. PMID- 26356262 TI - MicroRNA-29a Promotes Pancreatic Cancer Growth by Inhibiting Tristetraprolin. AB - BACKGROUND/AIMS: The microRNA (miR) 29 family has been studied extensively for its involvement in several diseases, and aberrant expression of its members is associated with tumorigenesis and cancer progression. Here, we examined the role of miR-29a in pancreatic cancer and the involvement of tristetraprolin (TTP). METHODS: We monitored miR-29a and TTP expression in pancreatic cancer by qRT-PCR and western blotting. The effect of miR-29a on pancreatic cancer was determined through MTT assay and migration assay. The results were validated in the tumorigenesis model. RESULTS: We found that miR-29a was up regulated in pancreatic tumor tissues and cell lines and positively correlated with metastasis. Ectopic expression of miR-29a increased the expression of pro inflammatory factors and epithelial-mesenchymal transition (EMT) markers, through down regulating TTP. TTP was down regulated in tumor tissues, and its ectopic expression decreased cell viability and migration in vitro, inhibited tumor growth and the EMT phenotype in vivo, and reversed the effect of miR-29a on tumor cell proliferation and invasion in vitro and in vivo. CONCLUSION: Our results suggest that miR-29a acts as an oncogene by down regulating TTP and provide the basis for further studies exploring the potential of miR-29a and TTP as biomarkers and targets for the treatment of pancreatic cancer. PMID- 26356263 TI - Histone Demethylase JMJD2A Inhibition Attenuates Neointimal Hyperplasia in the Carotid Arteries of Balloon-Injured Diabetic Rats via Transcriptional Silencing: Inflammatory Gene Expression in Vascular Smooth Muscle Cells. AB - BACKGROUND/AIMS: Diabetic patients suffer from severe neointimal hyperplasia following angioplasty. The epigenetic abnormalities are increasingly considered to be relevant to the pathogenesis of diabetic cardiovascular complications. But the epigenetic mechanisms linking diabetes and coronary restenosis have not been fully elucidated. In this study, we explored the protective effect and underlying mechanisms of demethylases JMJD2A inhibition in balloon-injury induced neointimal formation in diabetic rats. METHODS: JMJD2A inhibition was achieved by the chemical inhibitor 2,4-pyridinedicarboxylic acid (2,4-PDCA) and small interfering RNA (siRNA). In vitro, we investigated the proliferation, migration and inflammation of rat vascular smooth muscle cells (VSMCs) in response to high glucose (HG). In vivo, diabetic rats induced using high-fat diet and low-dose streptozotocin (35mg/kg) underwent carotid artery balloon injury. Morphometric analysis was performed using hematein eosin and immumohistochemical staining. Chromatin Immunoprecipitation (ChIP) was conducted to detect modification of H3K9me3 at inflammatory genes promoters. RESULTS: The global JMJD2A was increased in HG-stimulated VSMCs and balloon-injured arteries of diabetic rats, accompanied by decreased H3K9me3. The inhibition of JMJD2A suppressed VSMCs proliferation, migration and inflammation induced by high glucose (HG) in vitro. And JMJDA2A inhibition attenuated neointimal formation in balloon-injured diabetic rats. The underlying mechanisms were relevant to the restoration of H3K9me3 levels at the promoters of MCP-1 and IL-6, and then the suppressed expression of MCP-1 and IL 6. CONCLUSION: The JMJD2A inhibition significantly attenuated neointimal formation in balloon injured diabetic rats via the suppression of VSMCs proliferation, migration, and inflammation by restoring H3K9me3. PMID- 26356264 TI - Regular Exercise Enhances the Immune Response Against Microbial Antigens Through Up-Regulation of Toll-like Receptor Signaling Pathways. AB - BACKGROUND/AIMS: Regular physical exercise can enhance resistance to many microbial infections. However, little is known about the mechanism underlying the changes in the immune system induced by regular exercise. METHODS: We recruited members of a university badminton club as the regular exercise (RE) group and healthy sedentary students as the sedentary control (SC) group. We investigated the distribution of peripheral blood mononuclear cell (PBMC) subsets and functions in the two groups. RESULTS: There were no significant differences in plasma cytokine levels between the RE and SC groups in the true resting state. However, enhanced levels of IFN-gamma, TNF-alpha, IL-6, IFN-alpha and IL-12 were secreted by PBMCs in the RE group following microbial antigen stimulation, when compared to the SC group. In contrast, the levels of TNF-alpha and IL-6 secreted by PBMC in the RE group were suppressed compared with those in SC group following non-microbial antigen stimulation (concanavalin A or alpha-galactosylceramide). Furthermore, PBMC expression of TLR2, TLR7 and MyD88 was significantly increased in the RE group in response to microbial antigen stimulation. CONCLUSION: Regular exercise enhances immune cell activation in response to pathogenic stimulation leading to enhanced cytokine production mediated via the TLR signaling pathways. PMID- 26356265 TI - Role of Na+-K+-2Cl- Cotransporter 1 in Phenylephrine-Induced Rhythmic Contraction in the Mouse Aorta: Regulation of Na+-K+-2Cl- Cotransporter 1 by Ca2+ Sparks and KCa Channels. AB - BACKGROUND/AIMS: Vasoconstrictor-induced rhythmic contraction of arteries or veins has been observed both in vivo and in vitro. Many studies have reported that gap junctions, ryanodine receptors, Na+, K+-ATPase and other factors are involved in vasoconstrictor-induced rhythmic contraction in vascular smooth muscle. However, the mechanism is still not completely understood. METHODS: We used vessel tension measurements, intracellular recordings and intracellular Cl- concentration ([Cl-]i) measurements to investigate the mechanism underlying phenylephrine (PE)-induced rhythmic contraction in the mouse aorta. RESULTS: We found that Na+-K+-2Cl- cotransporter 1 (NKCC1) inhibitor bumetanide abolished PE induced rhythmic contraction. The Cl- channel blockers DIDS and niflumic acid initially augmented the amplitude of PE-induced rhythmic contraction but later inhibited the rhythmic contraction. The large Ca2+-activated K+ channel blocker TEA and iberiotoxin increased the amplitude of PE-induced rhythmic contraction. The voltage-dependent Ca2+ channel blocker, nifedipine, and a Ca2+-free solution abolished PE-induced rhythmic contraction. The inhibitor of ryanodine receptors in the sarcoplasmic reticulum, ryanodine, inhibited PE-induced rhythmic contraction. Moreover, bumetanide hyperpolarized the membrane potential of vascular smooth muscle cells in a resting state or after PE pre-treatment. Bumetanide, niflumic acid, ryanodine, iberiotoxin, nifedipine and Ca2+-free buffer significantly suppressed the PE-induced [Cl-]i increase. CONCLUSION: These data indicate that NKCC1 is involved in the formation of PE-induced rhythmic contraction, and we also provide a method with which to indirectly observe the NKCC1 activity in isolated intact mouse thoracic aortas. PMID- 26356266 TI - Angiotensin-Converting Enzyme 2 Inhibits Apoptosis of Pulmonary Endothelial Cells During Acute Lung Injury Through Suppressing MiR-4262. AB - BACKGROUND/AIMS: Angiotensin converting enzyme 2 (ACE2) treatment suppresses the severity of acute lung injury (ALI). The effects of ACE2 in ALI have been shown to not only result from its antagonizing hydrolyzing angiotensin II (AngII), which is responsible for reduction in the vascular tension and pulmonary accumulation of inflammatory cells, but also result from a role of ACE2 in suppressing the ALI-induced apoptosis of pulmonary endothelial cells (PECs). Nevertheless, the underlying mechanisms of the role of ACE2 on PEC apoptosis are not completely understood. METHODS: Here, we used a bleomycin-induced mouse model for ALI that has been published in our previous studies. We analyzed the mRNA and protein levels of an anti-apoptotic protein Bcl-2 in the ALI-mice that have been treated w/o ACE2. We analyzed miR-4262 levels in the mouse lung in these mice. Bcl-2-targeting miRNAs were predicted using bioinformatics algorithms and a luciferase reporter assay was applied to examine the effects of miR-4262 on the Bcl-2 protein translation upon their binding to 3'-UTR of Bcl-2 mRNA. Adeno associated viruses carrying either miR-4262 mimics or antisense were injected into ALI-mice without ACE2, and their effects on the apoptosis in mouse lung cells were analyzed by Western blot. RESULTS: ACE2 inhibited the ALI-induced apoptosis of pulmonary cells in vivo partially through upregulation of Bcl-2 protein, but not Bcl-2 mRNA. ACE2 appeared to significantly suppress the upregulation of miR-4262 in mouse lung after ALI. MiR-4262 was found to target 3' UTR of Bcl-2 mRNA to inhibit its protein translation in PECs. In vivo administration of antisense of miR-4262 decreased apoptosis of pulmonary cells and severity of the ALI in mice. CONCLUSION: ACE2-induced suppression of miR-4262 partially contribute to the inhibition of the PEC apoptosis after ALI through Bcl 2. MiR-4262 may be a novel promising treatment target for ALI and ARDS. PMID- 26356267 TI - Triggering of Suicidal Erythrocyte Death by Ruxolitinib. AB - BACKGROUND/AIMS: The JAK1/JAK2 tyrosine kinase inhibitor ruxolitinib is widely used for the treatment of myeloproliferative neoplasm-associated myelofibrosis and other malignancies. Most important side effects include anemia. A common cause of anemia is accelerated suicidal death of erythrocytes or eryptosis, which is characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Mechanisms contributing to the triggering of eryptosis include oxidative stress, Ca2+ entry with increase of cytosolic Ca2+ activity ([Ca2+]i), and activation of distinct kinases, such as p38 mitogen activated protein (MAP) kinase. The present study explored whether and how ruxolitinib induces eryptosis. METHODS: Phosphatidylserine exposure at the cell surface was estimated from annexin-V binding, cell volume from forward scatter, hemolysis from hemoglobin release, [Ca2+]i from Fluo3-fluorescence, and ROS formation from DCFDA dependent fluorescence. RESULTS: A 48 hours exposure of human erythrocytes to ruxolitinib (25 uM) significantly increased the percentage of annexin-V-binding cells and significantly decreased forward scatter. Ruxolitinib did not significantly modify Fluo3-fluorescence and DCFDA fluorescence and the effect of ruxolitinib on annexin-V-binding was not significantly modified by removal of extracellular Ca2+. The effect of ruxolitinib on annexin-V-binding was, however, significantly blunted by the p38 MAP kinase inhibitor SB203580 and virtually abolished by the p38 MAP kinase inhibitor skepinone. CONCLUSION: Ruxolitinib triggers cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane, an effect in part requiring p38 MAP kinase activity. PMID- 26356268 TI - Spongionella Secondary Metabolites Regulate Store Operated Calcium Entry Modulating Mitochondrial Functioning in SH-SY5Y Neuroblastoma Cells. AB - BACKGROUND/AIMS: The effect of four secondary metabolites isolated from sponge Spongionella, gracilins H, A, L and tetrahydroaplysulphurin-1 on Calcium ion (Ca2+) fluxes were studied in SH-SY5Y neuroblastoma cells. METHODS AND RESULTS: These compounds did not modify cytosolic baseline Ca2+-levels. Nevertheless, when cytosolic Ca2+-influx through store operated calcium channels (SOC channels) was stimulated with Thapsigargin (Tg), a strong inhibition was observed in the presence of gracilin A, gracilin L and tetrahydroaplysulphurin-1. Since these compounds were able to protect mitochondria from oxidative stress, the role of this organelle in the Ca2+-influx inhibition was tested. In this sense, carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone (FCCP) and Cyclosporine A (CsA) were used. Surprisingly, both the inhibitory effect over Tg-sensitive stores and Ca2+ influx through SOC channels produced by FCCP were abolished with different potencies by Spongionella compounds in a similar way than CsA. CsA is able to avoid Mitochondrial Permeability Transition Pore (mPTP) opening. As well as CsA, Spongionella compounds reverted mPTP opening induced by FCCP. In the case of CsA the mPTP blockade is due to the direct binding to Cyclophilin D (Cyp D), a mitochondrial matrix protein. This association was also observed between gracilin L and tetrahydroaplysulphurin-1 and Cyp D. Therefore, Spongionella compounds modulate mitochondrial activity by preventing mPTP opening by binding to Cyp D. CONCLUSIONS: These effects make Spongionella compounds as new family of compounds with promising activity in human diseases where mitochondrial alterations are implicated. PMID- 26356269 TI - TGF-beta Induces Up-Regulation of Chondroitin Sulfate Synthase 1 (CHSY1) in Nucleus Pulposus Cells Through MAPK Signaling. AB - BACKGROUND/AIMS: Chondroitin sulfate synthase 1 (CHSY1) is a glycosyltransferases involved in the biosynthesis of chondroitin and dermatan sulfate glycosaminoglycan (GAG). TGF-beta can stimulate sulfated GAG production in nucleus pulposus cells; however, the underlying mechanisms are poorly understood. METHODS: CHSY1 expression was examined in rat nucleus pulposus treated with TGF beta using real-time PCR and Western blot analysis. Lentiviral knockdown was performed to determine the downstream effectors of TGF-beta and to measure the effect of c-Jun and Sp1 on TGF-beta mediated CHSY1 promoter activity and CHSY1 expression. RESULTS: TGF-beta increased CHSY1 expression and promoter activity in the nucleus pulposus partially through activation of canonical Smad signaling pathway. Knockdown of c-Jun and Sp1 decreased CHSY1 promoter activity, CHSY1 expression and sGAG accumulation induced by TGF-beta. Furthermore, we found that TGF-beta-induced expression of CHSY1 was mediated through the activation of MAPK signaling. Moreover, we showed that silencing CHSY1 decreased sGAG accumulation in nucleus pulposus cells induced by TGF-beta. CONCLUSION: Our results suggest that TGF-beta induced CHSY1 expression in the nucleus pulposus through the activation of MAPK signaling. PMID- 26356270 TI - Stimulation of Suicidal Erythrocyte Death by Garcinol. AB - BACKGROUND/AIMS: The benzophenone garcinol from dried fruit rind of Garcinia indica counteracts malignancy, an effect at least in part due to stimulation of apoptosis. The proapototic effect of garcinol is attributed in part to inhibition of histone acetyltransferases and thus modification of gene expression. Moreover, garcinol triggers mitochondrial depolarisation. Erythrocytes lack gene expression and mitochondria but are nevertheless able to enter apoptosis-like suicidal death or eryptosis, which is characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Stimulators of eryptosis include oxidative stress, energy depletion and Ca2+ entry with increase of cytosolic Ca2+ activity ([Ca2+]i). The present study explored, whether and how garcinol induces eryptosis. METHODS: To this end, phosphatidylserine exposure at the cell surface was estimated from annexin-V binding, cell volume from forward scatter, hemolysis from hemoglobin release, [Ca2+]i from Fluo3-fluorescence, ROS formation from DCFDA dependent fluorescence and cytosolic ATP levels utilizing a luciferin-luciferase-based assay. RESULTS: A 24 hours exposure of human erythrocytes to garcinol (2.5 or 5 uM) significantly increased the percentage of annexin-V-binding cells. Garcinol decreased (at 1 uM and 2.5 uM) or increased (at 5 uM) forward scatter. Garcinol (5 uM) further increased Fluo3-fluorescence, increased DCFDA fluorescence, and decreased cytosolic ATP levels. The effect of garcinol on annexin-V-binding was significantly blunted, but not abolished by removal of extracellular Ca2+. CONCLUSIONS: Garcinol triggers cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane, an effect in part due to stimulation of ROS formation, energy depletion and Ca2+ entry. PMID- 26356271 TI - Cryptotanshinone Reverses Cisplatin Resistance of Human Lung Carcinoma A549 Cells through Down-Regulating Nrf2 Pathway. AB - BACKGROUND/AIMS: To explore whether Nrf2 was associated with drug-resistance in cisplatin resistant A549 (A549/DDP) cells, and if cryptotanshinone (CTS), one of the bioactive compounds isolated from the roots of Salvia miltiorrhiza Bunge (Danshen), could enhance the sensitivity in A549/DDP cells towards cisplatin. METHODS: A549 and A549/DDP cells were subjected to various treatments, and then Sulforhodamine B (SRB) assay, flow cytometry analysis and western immunoblotting analysis were applied to determine IC50, apoptotic status and expressions of Nrf2 and its downstream genes. RESULTS: The endogenous expression levels of Nrf2 as well as its target genes including GCLC, GCLM, HO-1, NQO1 and MRP1 were much higher in A549/DDP cells than those of A549 cells and the susceptibility of A549/DDP cells to cisplatin was partially restored by silencing Nrf2. The combination of CTS and cisplatin led to cell death and apoptosis through sensitizing A549/DDP cells towards cisplatin compared with cisplatin mono treatment, however, this reversal role could be abolished by Nrf2 knockdown. Specifically, CTS obviously diminished Nrf2 expression, thus contributing to the decrease of Nrf2-target genes expression levels. Meanwhile, we also discovered that CTS triggered several other signals involving in chemoresistance such as MAPKs, Akt and STAT3 pathway. CONCLUSION: Our data indicated CTS may be developed as a potential sensitizer cooperating with anticancer drugs to combat chemoresistant carcinoma through the inhibition of the Nrf2 pathway. PMID- 26356272 TI - Branching ratios for the reactions of OH with ethanol amines used in carbon capture and the potential impact on carcinogen formation in the emission plume from a carbon capture plant. AB - The OH initiated gas-phase chemistry of several amines that are potential candidates for use in post-combustion carbon capture (PCCC) plants have been studied by laser flash photolysis with OH monitored by laser induced fluorescence. The rate coefficients for the reaction of OH with N methylethanolamine (MMEA) and N,N-dimethylethanolamine (DMEA) have been measured as a function of temperature (~300-500 K): k(OH+MMEA) = (8.51 +/- 0.65) * 10( 11)(T/298)(-(0.79+/-0.22), k(OH+DMEA) = (6.85 +/- 0.25) * 10(-11)(T/298)(-(0.44+/ 0.12). The results for DMEA lie between previous values. This is the first kinetic study of the OH + MMEA reaction. At low pressures in the presence of oxygen, OH is recycled in the DMEA reaction as has been observed for other tertiary amines. Branching ratios for OH abstraction with MEA, DMEA and MMEA are dominated by abstraction from the alphaCH2 group. Abstraction from N-H is determined to be 0.38 +/- 0.06 for MEA and 0.52 +/- 0.06 for MMEA at 298 K. The impact of these studies has been assessed by using a modified chemical box model to calculate downwind concentrations of nitramines and nitrosamine formed in the photo-oxidation of MEA. Under clear sky conditions, the simulations suggest that current safe guidelines for nitramines may be significantly exceeded with predicted MEA emission rates. PMID- 26356273 TI - [Pathological fantasies in children]. AB - AIM: To develop a clinical classification of pathological fantasies (fantasy syndrome) in children and adolescents regardless of nosological attribution. MATERIAL AND METHODS: We examined 109 patients, aged 3-16 years, using psychopathological and instrumental (EEG and MRI) methods. RESULTS AND CONCLUSION: Authors developed the clinical typology of pathological fantasies in children with different mental diseases and disorders. The following variants of fantasy syndromes were singled out: 1. fantasizing with sensorealization of mental images; 2. fantastic stories (subdivided into 5 different variants): 2.1 easily provoked fantasies with situation-conditioned content; 2.2. fantasizing with increased falsehood; 2.3. sexual allegations and self-accusations; 2.4. fantasizing about imaginary worlds; 2.5. fantasies about a fictional friend); 3. playing transformation; 4. fantasies with a predominance of specific hobbies. PMID- 26356274 TI - [Somatopsychic synergism as a variant of masked depression in children and adolescents]. AB - AIM: To analyze a variant of a combination of psychopathological (subdepressive) state with inflammatory diseases of non-specific infectious origin. MATERIAL AND METHODS: The paper was based on the study of 45 patients, aged from 12 to 19 years, examined using psychopathological and follow-up methods. A detailed somatic examination was performed as well. RESULTS AND CONCLUSION: Authors described a phenomenon of somatopsychic synergism as a variant of a combination of somatic pathology (adenoviral and coccus infections) with subclinical affective syndromes of cyclothymic and schizophrenic origin. This phenomenon is opposed to somatopsychic antagonism which is qualified as a specific form of masked subdepressive states predominantly of asthenic/dynamic structure. PMID- 26356275 TI - [Characteristics of neurological status in children with schizophrenia and schizotypal disorder]. AB - AIM: To study characteristics of neurological status in children with schizophrenia and schizotypal disorder. MATERIAL AND METHODS: A study included 80 children, aged from 5 to 10 years: 38 children were diagnosed with schizophrenia (ICD-10 F20.8xx3) and 42 with schizotypal disorder (F21). RESULTS AND CONCLUSION: Children of both groups had a wide spectrum of neurological symptoms, diffuseness of which indicated the disintegration of the multilevel system of motor analyzer. No topical between-group differences were found whereas their intensity and frequency was not correlated to either the severity or a stage (exacerbation - remission) of disease. The more marked was disease progression and severity of mental disorders, the greater was the amount and clearness of neurological disorders. There was a predominance of disorders of motor regulation and integration, various extrapyramidal disturbances. As a consequence, in absence of paresis and paralyses, there was not merely the alteration of the function per se but rather of its integrity, completeness, consistency with other mental acts that turned to be the neurologic equivalent of discordance and inconsistency of mental functions specific of schizophrenia. These neurological symptoms may be considered as topic markers of the changes in the brain and dynamics of endogenous process. Transitory and instable character of these symptoms, along with the deficits of extrapyramidal and cortical regulation outside of the process exacerbation, indicates the insufficiency of neurotransmitter mechanisms. PMID- 26356276 TI - [On the problem of psychological (psychometric) diagnosis of intelligence in children with developmental disorders]. AB - A review includes the following sections corresponded with methods of investigation and groups of patients: Wechsler test for atypical autism and schizophrenia; Psycho Educational Profile (PEP) in endogenous mental pathology, the Kaufman Test of Educational Achievement in children schizophrenia, Edinburgh Picture Test in mental dysontogenesis. The results of the studies in these fields are presented. PMID- 26356277 TI - [Arterial ischemic stroke in children with mild head trauma]. AB - AIM: To study the relationship between mild head trauma (MHT) and arterial ischemic stroke (AIS) in children. MATERIAL AND METHODS: We examined 81 patients with AIS, aged from 1 month to 15 years. The sample was stratified into two groups: patients with AIS caused by MHT (main group) and patients without MHT (comparison group). RESULTS AND CONCLUSION: Based on the results of clinical and instrumental studies, we identified the relationship between AIS and MHT. The main group was characterized by the following features: moderate severity in the acute period, stabilization within 7 days, isolated subcortical localization of ischemic lesion, no MRI-signs of steno-occlusive cerebral arteriopathy and a trend towards the risk of recurrent strokes. PMID- 26356278 TI - [Selection of a dose of the botulinum toxin A in spastic forms of cerebral palsy]. AB - AIM: To analyze the efficacy and safety of dose ranges of abobotulinum toxin A (BTA) for multilevel injections into upper and lower extremity muscles in children with spastic forms of cerebral palsy (CP). MATERIAL AND METHODS: We analyzed retrospectively multilevel BTA injections for 216 patients, aged from 2 to 17 years. Children received 1-6 repeated injections and complex physiotherapy. Patients were classified according to the GMFCS. Treatment results were evaluated with the modified Ashworth and Tardieu scales. RESULTS: Multilevel BTA injections were indicated for the most (89/8%) of the patients with spastic forms of CP, and in most of them the total dosage exceeded 30 U/kg. In the bilateral forms of CP, the total dosage (U and U/kg) was higher compared to the unilateral forms. Doses for each muscle in U/kg were similar in all CP forms. The total doses of BTA and the intervals between the repeated injections were stable for each patient. CONCLUSION: The dose ranges suggested for CP are effective and safe for the reduction of spasticity in several functional segments of upper and lower extremities in one treatment session. PMID- 26356279 TI - [Asthenia in adolescents with attention deficit disorder and their treatment]. AB - AIM: To study asthenia in adolescents with attention deficit hyperactivity disorder (ADHD) and assess the efficacy of nooclerin. MATERIAL AND METHODS: We examined 60 patients, aged from 12 to 15 years, with ADHD. A comparative analysis of ADHD demonstrated the predominance of an inattentive type (ADHD-I) and a combined type (ADHD-C). RESULTS AND CONCLUSION: Symptoms of asthenia were found in 56% of adolescents with ADHD-C and in 96.7% with ADHD-I. The high efficacy and safety of nooclerin in the treatment of ADHD was demonstrated. The improvement of mental state was achieved in 76.7% of patients with ADHD-I and in 53.3% patients with ADHD-C. PMID- 26356280 TI - [The influence of premorbid functioning on the efficacy of psychosocial therapy in adolescents with schizophrenia spectrum disorders]. AB - AIM: To explore an effect of premorbid functioning level on the efficacy of psychosocial therapy in adolescents with schizophrenia spectrum disorders in order to determine a differential approach to its performance. MATERIAL AND METHODS: A study included 53 adolescents with schizophrenia spectrum disorders at the early stage of remission achievement (PANSS scores <65). An impact of premorbid functioning was assessed with the DD-CGAS and the efficacy of psychosocial therapy with CGAS and PedsQL at baseline and after 3, 6 and 12 months. RESULTS AND CONCLUSION: We described the most relevant differences in characteristics of treatment effect (dc) between three groups with different levels of premorbid functioning. To increase the efficacy of psychosocial interventions, we suggest a differential approach of psychosocial therapy in each group. PMID- 26356281 TI - [Experience of using ketogenic diet in a patient with glucose transporter 1 deficiency syndrome (a case report)]. AB - We present the experience of using the ketogenic diet (KD) in the treatment of pharmacoresistant epilepsy in a patient with glucose transporter deficiency syndrome type I (GLUT1). We observed a nine-year-old boy with refractory epilepsy with frequent multiple myoclonic seizures due to GLUT1. The high effectiveness of KD in the treatment of GLUT1 was demonstrated. By the 10th day from the beginning of KD, a complete relief of epileptic seizures and EEG abnormalities was achieved. After 3 months, we noticed positive signs in cognitive and speech development of the child. Antiepileptic drugs were withdrawn due to the stable remission. Subsequently there was a further positive dynamics in intelligence, psycho-emotional sphere; the child began attending a special school. By this time the patient continued the diet for 1 year and 3 months. A significant improvement in the patient's condition is maintained, observation is being continued. IN CONCLUSION: the ketogenic diet seems to be a highly effective and, perhaps, exclusive method for GLUT1 treatment. PMID- 26356282 TI - [Neurotropic, anti-inflammatory and antitumor properties of hopantenic acid: a chemoinformatic analysis of its molecule]. AB - Hopantenic acid is a well-known nootropic drug similar in its chemical structure to pantothenic acid (vitamin B5). Neurotropic effects of hopantenic acid act through binding with delta- and kappa opioid receptors, modulation of acetylcholine secretion and relationship with dopamine receptors. Besides neurotropic effects, hopantenic acid may modulate the metabolism of prostaglandins, steroids and have antitumor effects. PMID- 26356283 TI - Preoperative CT-Angiography Predicts Ex Vivo Vein Length for Right Kidneys After Laparoscopic Donor Nephrectomy. AB - BACKGROUND Implantation of a kidney with a short renal vein is technically more challenging and therefore prone for technique-related complications. It remains unclear whether pre-operative computed tomography angiography (CTA), to assess vascular anatomy of the donor kidney, can be used to predict renal vein length. MATERIAL AND METHODS Right and left renal vein lengths of 100 consecutive kidney donors were measured in an oblique-coronal plane multiplanar reconstruction image of 100 consecutive kidney donors in whom ex vivo vein length was measured after recovery. In a second retrospective cohort of 100 consecutive kidney donors donating a right kidney, preoperative CTA vein length measurements were correlated to anastomosis time and early graft outcome. RESULTS Left and right renal vein lengths, measured on CTA, were 43.2 mm and 30.0 mm, respectively. No correlation was found between CTA and ex vivo measurements for the left renal vein (p=.610), whereas a significant correlation was found for the right renal vein (p=.021). In the retrospective cohort, right renal vein length was significantly correlated with the anastomosis time but not with early graft outcome. CONCLUSIONS The length of the right, but not the left, renal vein can be predicted by preoperative CTA, but this does not hold true for the left renal vein. PMID- 26356284 TI - Optical Control of Mechanical Mode-Coupling within a MoS2 Resonator in the Strong Coupling Regime. AB - Two-dimensional (2-D) materials including graphene and transition metal dichalcogenides (TMDs) are an exciting platform for ultrasensitive force and displacement detection in which the strong light-matter coupling is exploited in the optical control of nanomechanical motion. Here we report the optical excitation and displacement detection of a ~ 3 nm thick MoS2 resonator in the strong-coupling regime, which has not previously been achieved in 2-D materials. Mechanical mode frequencies can be tuned by more than 12% by optical heating, and they exhibit avoided crossings indicative of strong intermode coupling. When the membrane is optically excited at the frequency difference between vibrational modes, normal mode splitting is observed, and the intermode energy exchange rate exceeds the mode decay rate by a factor of 15. Finite element and analytical modeling quantifies the extent of mode softening necessary to control intermode energy exchange in the strong coupling regime. PMID- 26356285 TI - Respiratory Failure in an Adolescent with Primary Cardiac Sarcoma. AB - We report a case of progressive respiratory failure secondary to primary cardiac sarcoma masquerading as primary lung disease. An 18-year-old female presented to our hospital emergency department with progressive cough, dyspnea, and hemoptysis. She was treated for primary lung infection without improvement and had respiratory failure with endotracheal intubation by the third hospital day. An "intermediate" plasma brain natriuretic protein (BNP) of 216 pg/mL did not raise concerns about a heart failure diagnosis and may have delayed the correct diagnosis. Computed tomography of the chest with intravenous contrast was performed on the fifth hospital day and revealed a cardiac mass. A transthoracic echocardiogram confirmed a large left atrial mass that was obstructing mitral inflow. She was transferred to a tertiary center for emergency cardiac surgery. Primary cardiac tumors are a rare and treatable cause of heart failure in adolescent and young adult patients. Presentation can be confused with primary lung disease and must be suspected early. Plasma BNP cutoff levels used in the adult population should not be extrapolated to adolescents, as levels, both normal and abnormal, are significantly lower in this group of patients. PMID- 26356286 TI - A study on physical status and life satisfaction of workers. AB - [Purpose] This study was conducted to examine physical status and life satisfaction of workers in Korea. [Subjects] In total, 25,455 workers from eight geographical areas were evaluated from 2007 to 2008. [Methods] Physical status of the subjects was measured based on cardiopulmonary endurance, muscular strength, muscular endurance, flexibility, and explosive muscular strength, and a life satisfaction index was used to measure life satisfaction. [Results] Higher levels of cardiopulmonary endurance, muscular strength, muscular endurance, flexibility, and explosive muscular strength of workers were correlated with higher life satisfaction. [Conclusion] The result suggests it is necessary to improve life satisfaction through continuous health management of workers. PMID- 26356287 TI - The Cost of Responding to an Acinetobacter Outbreak in Critically Ill Surgical Patients. AB - BACKGROUND: Our institution had an outbreak of multi-drug-resistant Acinetobacter (MDRA) in 2011. We analyzed the costs of responding to this outbreak from the hospital's perspective. METHODS: We estimated retrospectively the excess costs associated with an MDRA outbreak response at a major academic medical center, including the costs of staffing, supplies, administrative time, deep cleaning, and environmental testing. Differences in mean costs before and during the 2011 MDRA outbreak were analyzed using the Student t-test. RESULTS: The overall excess cost incurred during the outbreak response was $371,079 in 2011 U.S. dollars. The largest contributors were the extra resources needed to staff and clean the two intensive care units (ICUs) (78%). In the general surgery ICU, the mean weekly cost of nursing during the outbreak was $13,276 more for regular hours (+15%; p < 0.01) than in the pre-outbreak period and $2,682 more for overtime hours (+86%; p = 0.02). In the trauma ICU, the cost was $20,746 more for regular hours (+24%; p < 0.01) and $3,445 more for overtime hours (+124%; p < 0.01). The costs of supplies ($13,036; +30%; p = 0.03) and gloves ($2,572; +48%; p = 0.01) also were greater during the outbreak. Administrative time, consumables, use of a surge pod, and environmental testing accounted for the remainder of the extra costs. CONCLUSIONS: Our institution incurred $371,079 in excess costs as a result of an MDRA outbreak. This figure does not include the costs related to treatment of the infections, loss of reimbursement because of hospital-acquired infection, legal services, or changes in staff morale, patient satisfaction, or hospital reputation. Strategies to prevent and control such outbreaks better have substantial value. PMID- 26356288 TI - Inter-hemispheric functional and anatomical connectivity abnormalities in traffic accident-induced PTSD: a study combining fMRI and DTI. AB - BACKGROUND: Aberrant brain functional and structural changes are considered to be one of the important mechanisms underlying post-traumatic stress disorder (PTSD). However, it remains unclear whether inter-hemispheric connection is changed. The current study aimed to identify the inter-hemispheric functional and anatomical connectivity changes in patients who consequently develop PTSD using the voxel mirrored homotopic connectivity (VMHC) analysis and diffusion tractography techniques. METHODS: Resting-state fMRI and DTI data were acquired on victims who had experienced traffic accidents within 2 days after the traumatic event. The diagnosis was made using the Clinician-Administered PTSD Scale at 1 or 6 months later. Fifteen trauma-exposed victims met the criteria for diagnosis of PTSD and 14 trauma-exposed victims who did not develop PTSD at 6 months after trauma were selected as the control group. RESULTS: Compared with the victims without PTSD, the victims with PTSD exhibited an abnormal homotopic pattern with decreased VMHC in the superior/middle frontal gyrus before diagnosis. The regions showing abnormal functional connectivity were then chosen as regions of interest for an analysis of DTI tractography. Decreased fractional anisotropy values in the genu of the corpus callosum were found in the victims with PTSD. Greater WM disruptions within 2 days predicted greater symptom severity at diagnosis. LIMITATIONS: The study was lack of comparison with controls who did not experience a traumatic event. CONCLUSION: Our results suggest that the inter hemispheric functional and structural connectivity is impaired in PTSD within 2 days, which may be the potential marker showing predisposition towards developing PTSD. PMID- 26356290 TI - Adult procedural sedation: an update. AB - PURPOSE OF REVIEW: The increasing request for procedural sedation will create in the upcoming future the need for a specific training in delivering care to patients in a continuum of sedation, whose effects and adverse events are unpredictable. The main debate in the past years has been focused on using drugs that could have few adverse effects and could be considered well tolerated when administered by a nonanaesthesiologist. Propofol remains the most used drug for procedural sedation, but given its side-effects, its administration is limited and suggested only when an anaesthesiologist is available. The main studies recently appearing in the literature are focusing on the use of alternative drugs such as dexmedetomidine, remifentanil, fospropofol, ketofol and remimazolam. The current study is an overview of the different fields of procedural sedation, describing the evidence from the published studies and some upcoming studies. RECENT FINDINGS: Propofol is still considered as the drug of choice, and a recent study on its administration in the emergency department by nonanaesthesiologists has revealed a reduced number of adverse events. Dexmedetomidine is considered, at present, the most commonly used alternative to propofol, given its greater safety in terms of haemodynamic stability and lack of respiratory depression. Remifentanil has been suggested as the 'solo' drug during procedural sedation by target-controlled infusion, but it needs a controlled environment and skilled practitioners. Fosprofol and ketofol are new alternatives, but convincing studies that could support their wider use are absent. Remimazolam is another alternative whose efficacy is still to be determined. Most of the studies in the literature are debating on the training that the 'proceduralist' should undergo to deliver sedation safely and to manage any kind of adverse effect caused by it. SUMMARY: Recent studies on procedural sedation are still debating on the use of propofol by nonanaesthesiologists and are exploring the use of other sedatives and analgesics. The main goal in the future should be to have a clear curriculum on the role of the 'sedationalist' outside the operating room. PMID- 26356289 TI - Parental and comorbid epilepsy in persons with bipolar disorder. AB - BACKGROUND: Population-based studies have demonstrated an overrepresentation of bipolar disorder (BPD) in individuals with epilepsy. However, few studies have examined the reverse association, i.e. comorbid epilepsy in individuals selected based on BPD diagnosis. No previous population-based study having examined the co occurrence of BPD and epilepsy has adjusted for parental psychopathology. Such an adjustment is motivated by population-based studies reporting an overrepresentation of various types of parental psychiatric disorders in both BPD and epilepsy. Furthermore, an association between epilepsy in first-degree relatives and BPD has previously only been examined and demonstrated in a small clinical sample. The objective of this study is to examine the associations between parental and comorbid epilepsy and BPD, adjusting for parental psychopathology. METHODS: This nested case-control study identified 1861 cases with BPD, age up to 25 years, 3643 matched controls, and their parents from Finnish national registers. Conditional logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs) and two-sided significance limits of p<0.05. RESULTS: BPD was associated with comorbid epilepsy (adjusted OR 2.53, 95% CI: 1.73-3.70) but not with parental epilepsy. Epilepsy was found in 3.33% of cases versus 1.29% of controls, 2.69% of cases' parents versus 2.53% of controls' parents. LIMITATIONS: The diagnoses were register-based, not based on standardized procedures with direct ascertainment. CONCLUSIONS: An association between BPD and comorbid epilepsy persists even after adjusting for parental psychopathology. Lack of familial clustering of BPD and epilepsy would suggest that the elevated co-occurrence of these disorders is influenced by non-genetic factors. PMID- 26356291 TI - Continuous peripheral nerve blocks in the ambulatory setting: an update of the published evidence. AB - PURPOSE OF REVIEW: To review the evidence recently published involving the use of continuous peripheral nerve blocks (cPNBs) in the ambulatory setting. RECENT FINDINGS: New evidence exists involving the risks and benefits of cPNB in ambulatory patient populations such as pediatric ambulatory and postmastectomy patients. In addition, new related equipment is now available to facilitate ambulatory cPNB. SUMMARY: Recent advancements in equipment for cPNB facilitate the usage in the ambulatory setting. Research-supported ambulatory cPNB indications have expanded to include pediatric subpopulations and major breast surgery, while further evidence mounts for its efficacy in patient populations with previously demonstrated benefits, such as foot, ankle and shoulder surgery. PMID- 26356292 TI - Orphan diseases: impact for anesthesia practice. AB - PURPOSE OF REVIEW: Orphan diseases certainly have a challenging impact on anesthesia practice. Low prevalence by definition leads to a profound lack of evidence-based medical knowledge, and anesthetists usually cannot rely on personal experience for handling this unique group of patients. Then again, more than 7000 known orphan diseases are estimated to affect 5% of the general population in total. Therefore, it is imperative to have a universally valid approach to anesthesia for orphan diseases. RECENT FINDINGS: Patients suffering from orphan diseases will be in need of anesthesia for disease-related diagnostic and therapeutic procedures as well as unrelated elective and emergency surgery and may present themselves on all levels of medical care. Instead of itemizing specifics for each disorder and procedure, we rather present a structured - checklist-like - approach to individually prepare for anesthesia and will highlight the most relevant anesthesiological problems and possible countermeasures. We will discuss a variety of sources of information to gain specific disease knowledge and procedural advice and will close this review by discussing the limitations of anesthesia for orphan diseases. SUMMARY: Thanks to fast growing resources of knowledge, well tolerated and patient-oriented anesthesia is possible in spite of the inherent challenges of orphan diseases. We invite anesthetists to adapt, modify and improve our proposed structured approach to orphan anesthesia in the context of their daily practice. PMID- 26356293 TI - Safety-II and resilience: the way ahead in patient safety in anaesthesiology. AB - PURPOSE OF REVIEW: Anaesthesiology is a specialty with a remarkable track record regarding improvements in safety. Nevertheless, modern healthcare poses increasing demands on quality and outcome: more complexity, more patients with increasing risk-factors, more regulation from society concerning quality and outcome and finally more demand of the stakeholders for efficiency. This leads us to ask the question if our traditional way of handling 'risk' and 'safety' will stand the challenges of the future? RECENT FINDINGS: Most of the success of modern anaesthesiology results from improved technology, pharmacology, training and education, improved systems, focus on human performance as well as standardization and development of guiding information. All of these aspects are crucial and have their relevance for well tolerated and modern practice. But despite all of these achievements, we must face the fact that we still cannot control complex processes by application of linear thinking (standardization). Modern risk-management concepts in other ultra-safe systems such as civil aviation or air traffic control introduced the concept of 'resilience' as well as 'safety-II' in order to deal with the challenges of increasing complex conditions. SUMMARY: We are well advised to consider adapting these modern concepts of 'resilience' and 'safety-II' thinking when we want to substantially improve patient safety in anaesthesiology. PMID- 26356294 TI - Airway management for anaesthesia in the ambulatory setting. AB - PURPOSE OF REVIEW: The number of anaesthetic procedures in the ambulatory setting is steadily increasing. During the last years, more and more patients with complex medical conditions undergo ambulatory interventions. This review will focus on airway management practices, but especially on techniques used in the ambulatory setting. It will highlight recent literature published in the focus of ambulatory anaesthesia and will discuss relevant findings of the last year. METHODS: Literature search and analysis performed independently by two reviewers. RECENT FINDINGS: Practical points to improve success of anaesthesia and to avoid complications in the ambulatory setting are provided. In addition to concepts for the (un)expected difficult airway, new supraglottic devices, and modern concepts for teleconsultation, are discussed. SUMMARY: There are several points which should be considered for ambulatory anaesthesia. Selected patient groups (e.g., obstructive sleep apnoea, obesity) may have a higher anaesthesia-related risk. To handle the more and more complex conditions in a growing number of ambulatory patients, straightforward concepts, especially for the (un)expected difficult airway, are required. PMID- 26356296 TI - Fast Generation of Sparse Random Kernel Graphs. AB - The development of kernel-based inhomogeneous random graphs has provided models that are flexible enough to capture many observed characteristics of real networks, and that are also mathematically tractable. We specify a class of inhomogeneous random graph models, called random kernel graphs, that produces sparse graphs with tunable graph properties, and we develop an efficient generation algorithm to sample random instances from this model. As real-world networks are usually large, it is essential that the run-time of generation algorithms scales better than quadratically in the number of vertices n. We show that for many practical kernels our algorithm runs in time at most ??(n(logn)2). As a practical example we show how to generate samples of power-law degree distribution graphs with tunable assortativity. PMID- 26356295 TI - Direct-acting Antiviral Agents for the Treatment of Chronic Hepatitis C Virus Infection. AB - Hepatitis C virus (HCV) is a leading cause of cirrhosis and hepatocellular carcinoma (HCC) in the US and Japan. Therefore, eradication of HCV may reduce the occurrence of HCC in HCV-infected individuals. In 2011, the use of first generation HCV NS3/4A protease inhibitors such as telaprevir and boceprevir was initiated for clinical treatment of HCV. Administration of telaprevir and boceprevir plus peginterferon and ribavirin increased rates of sustained virological response (SVR) in HCV genotype 1-infected patients. However, this treatment regimen also led to severe adverse events. Second-generation direct acting antiviral agents (DAAs) for HCV, such as simeprevir plus peg-interferon and ribavirin also resulted in higher SVR rates, with similar adverse events to other peg-interferon and ribavirin treatments. Higher SVR rates in HCV genotype 1 and 2-infected patients were achieved with 12-16 weeks of sofosbuvir plus other class DAAs with/without ribavirin and 12 weeks of sofosbuvir plus ribavirin, respectively. For "difficult-to-treat" HCV-infected patients, more therapeutic options are needed. Further studies examining the efficacy and adverse effects of such therapies will be required for the development of additional treatments. PMID- 26356297 TI - Fiat Luc: Bioluminescence Imaging Reveals In Vivo Viral Replication Dynamics. PMID- 26356298 TI - A Unique Set of the Burkholderia Collagen-Like Proteins Provides Insight into Pathogenesis, Genome Evolution and Niche Adaptation, and Infection Detection. AB - Burkholderia pseudomallei and Burkholderia mallei, classified as category B priority pathogens, are significant human and animal pathogens that are highly infectious and broad-spectrum antibiotic resistant. Currently, the pathogenicity mechanisms utilized by Burkholderia are not fully understood, and correct diagnosis of B. pseudomallei and B. mallei infection remains a challenge due to limited detection methods. Here, we provide a comprehensive analysis of a set of 13 novel Burkholderia collagen-like proteins (Bucl) that were identified among B. pseudomallei and B. mallei select agents. We infer that several Bucl proteins participate in pathogenesis based on their noncollagenous domains that are associated with the components of a type III secretion apparatus and membrane transport systems. Homology modeling of the outer membrane efflux domain of Bucl8 points to a role in multi-drug resistance. We determined that bucl genes are widespread in B. pseudomallei and B. mallei; Fischer's exact test and Cramer's V2 values indicate that the majority of bucl genes are highly associated with these pathogenic species versus nonpathogenic B. thailandensis. We designed a bucl based quantitative PCR assay which was able to detect B. pseudomallei infection in a mouse with a detection limit of 50 CFU. Finally, chromosomal mapping and phylogenetic analysis of bucl loci revealed considerable genomic plasticity and adaptation of Burkholderia spp. to host and environmental niches. In this study, we identified a large set of phylogenetically unrelated bucl genes commonly found in Burkholderia select agents, encoding predicted pathogenicity factors, detection targets, and vaccine candidates. PMID- 26356300 TI - Epidermal Micromorphology and Mesophyll Structure of Populus euphratica Heteromorphic Leaves at Different Development Stages. AB - Leaf epidermal micromorphology and mesophyll structure during the development of Populus euphratica heteromorphic leaves, including linear, lanceolate, ovate, dentate ovate, dentate rhombic, dentate broad-ovate and dentate fan-shaped leaves, were studied by using electron and light microscopy. During development of heteromorphic leaves, epidermal appendages (wax crystals and trichomes) and special cells (mucilage cells and crystal idioblasts) increased in all leaf types while chloroplast ultrastructure and stomatal characters show maximum photosynthetic activity in dentate ovate and rhombic leaves. Also, functional analysis by subordinate function values shows that the maximum adaptability to adverse stress was exhibited in the broad type of mature leaves. The 12 heteromorphic leaf types are classified into three major groups by hierarchical cluster analysis: young, developing and mature leaves. Mature leaves can effectively obtain the highest stress resistance by combining the protection of xerophytic anatomy from drought stress, regulation of water uptake in micro environment by mucilage and crystal idioblasts, and assistant defense of transpiration reduction through leaf epidermal appendages, which improves photosynthetic activity under arid desert conditions. Our data confirms that the main leaf function is differentiated during the developing process of heteromorphic leaves. PMID- 26356299 TI - Curbing Inflammation in Skin Wound Healing: A Review. AB - Wound healing is a complex regulated process that results in skin scar formation in postnatal mammals. Chronic wounds are major medical problems that can confer devastating consequences. Currently, there are no treatments to prevent scarring. In the early fetus wounds heal without scarring and the healing process is characterized by relatively less inflammation compared to adults; therefore, research aimed at reducing the inflammatory process related to wound healing might speed healing and improve the final scar appearance. PMID- 26356301 TI - Total syntheses of natural products containing spirocarbocycles. AB - The structures of natural products from a variety of sources contain spirocycles, two rings that share a common atom. The spiro motif is finding increasing inclusion in drug candidates, and as a structural component in several promising classes of chiral ligands used in asymmetric synthesis. Total syntheses of products containing all-carbon spirocycles feature several common methods of ring closure which we examine in this review. PMID- 26356303 TI - Plant Habitat-Conscious White Light Emission of Dy(3+) in Whitlockite-like Phosphates: Reduced Photosynthesis and Inhibition of Bloom Impediment. AB - It has been pointed out that agricultural crops and other natural plants may be damaged by outdoor lighting systems. Therefore, lighting that does not affect plant growth is needed. To address this problem, we have prepared a new whitlockite-like phosphate Dy-phosphor Ca8MgY1-x-yLaxDyy(PO4)7, which exhibits a yellow-white Dy(3+) luminescence that has a maximum internal quantum efficiency of 65.6% under a 387 nm excitation light for x = 0.10 and y = 0.05. The x dependence of IQE showed two maxima at x = 0.10-0.15 and 0.80-0.85, which could be due to the partial allowance of f-f forbidden transitions by local lattice distortion around the Dy(3+) ions originating from the La incorporation at near end members of Ca8MgY1-x-yLaxDyy(PO4)7. Concentration quenching occurred for x > 0.05. A white light-emitting diode (LED) was fabricated from a UV LED emitting at 385 nm and a Ca8MgY1-x-yLaxDyy(PO4)7 phosphor (Dy-WLED) for which the CIE color coordinates and correlated color temperature were CIE(0.350,0.378) and 4919 K, respectively. Plant cultivation experiments on Chlorella photosynthetic growth and blooming of the short-day plant Cosmos were carried out using the prepared Dy WLED and reference commercial LEDs. We found that the Dy-WLED substantially reduced the photosynthesis of Chlorella and inhibited bloom impediment in Cosmos. These effects originated especially from the reduction of red-near-IR emissions. Thus, we conclude that the Dy-WLED is a very promising candidate for plant habitat-conscious white LEDs for outdoor lights that can protect both natural plant habitats and crop yields. PMID- 26356302 TI - Identification of a plastidial phenylalanine exporter that influences flux distribution through the phenylalanine biosynthetic network. AB - In addition to proteins, L-phenylalanine is a versatile precursor for thousands of plant metabolites. Production of phenylalanine-derived compounds is a complex multi-compartmental process using phenylalanine synthesized predominantly in plastids as precursor. The transporter(s) exporting phenylalanine from plastids, however, remains unknown. Here, a gene encoding a Petunia hybrida plastidial cationic amino-acid transporter (PhpCAT) functioning in plastidial phenylalanine export is identified based on homology to an Escherichia coli phenylalanine transporter and co-expression with phenylalanine metabolic genes. Radiolabel transport assays show that PhpCAT exports all three aromatic amino acids. PhpCAT downregulation and overexpression result in decreased and increased levels, respectively, of phenylalanine-derived volatiles, as well as phenylalanine, tyrosine and their biosynthetic intermediates. Metabolic flux analysis reveals that flux through the plastidial phenylalanine biosynthetic pathway is reduced in PhpCAT RNAi lines, suggesting that the rate of phenylalanine export from plastids contributes to regulating flux through the aromatic amino-acid network. PMID- 26356304 TI - Rapid heterogeneous assembly of multiple magma reservoirs prior to Yellowstone supereruptions. AB - Large-volume caldera-forming eruptions of silicic magmas are an important feature of continental volcanism. The timescales and mechanisms of assembly of the magma reservoirs that feed such eruptions as well as the durations and physical conditions of upper-crustal storage remain highly debated topics in volcanology. Here we explore a comprehensive data set of isotopic (O, Hf) and chemical proxies in precisely U-Pb dated zircon crystals from all caldera-forming eruptions of Yellowstone supervolcano. Analysed zircons record rapid assembly of multiple magma reservoirs by repeated injections of isotopically heterogeneous magma batches and short pre-eruption storage times of 10(3) to 10(4) years. Decoupled oxygen-hafnium isotope systematics suggest a complex source for these magmas involving variable amounts of differentiated mantle-derived melt, Archean crust and hydrothermally altered shallow-crustal rocks. These data demonstrate that complex magma reservoirs with multiple sub-chambers are a common feature of rift- and hotspot related supervolcanoes. The short duration of reservoir assembly documents rapid crustal remelting and two to three orders of magnitude higher magma production rates beneath Yellowstone compared to continental arc volcanoes. The short pre-eruption storage times further suggest that the detection of voluminous reservoirs of eruptible magma beneath active supervolcanoes may only be possible prior to an impending eruption. PMID- 26356306 TI - Facile reversibility by design: tuning small molecule capture and activation by single component frustrated Lewis pairs. AB - A series of single component FLPs has been investigated for small molecule capture, with the finding that through tuning of both the thermodynamics of binding/activation and the degree of preorganization (i.e., DeltaS(?)) reversibility can be brought about at (or close to) room temperature. Thus, the dimethylxanthene system {(C6H4)2(O)CMe2}(PMes2)(B(C6F5)2): (i) heterolytically cleaves dihydrogen to give an equilibrium mixture of FLP and H2 activation product in solution at room temperature and (ii) reversibly captures nitrous oxide (uptake at room temperature, 1 atm; release at 323 K). PMID- 26356305 TI - Transient Receptor Potential Vanilloid 2 Regulates Myocardial Response to Exercise. AB - The myocardial response to exercise is an adaptive mechanism that permits the heart to maintain cardiac output via improved cardiac function and development of hypertrophy. There are many overlapping mechanisms via which this occurs with calcium handling being a crucial component of this process. Our laboratory has previously found that the stretch sensitive TRPV2 channels are active regulators of calcium handling and cardiac function under baseline conditions based on our observations that TRPV2-KO mice have impaired cardiac function at baseline. The focus of this study was to determine the cardiac function of TRPV2-KO mice under exercise conditions. We measured skeletal muscle at baseline in WT and TRPV2-KO mice and subjected them to various exercise protocols and measured the cardiac response using echocardiography and molecular markers. Our results demonstrate that the TRPV2-KO mouse did not tolerate forced exercise although they became increasingly exercise tolerant with voluntary exercise. This occurs as the cardiac function deteriorates further with exercise. Thus, our conclusion is that TRPV2-KO mice have impaired cardiac functional response to exercise. PMID- 26356307 TI - Amine-Oxide Hybrid Materials for CO2 Capture from Ambient Air. AB - Oxide supports functionalized with amine moieties have been used for decades as catalysts and chromatographic media. Owing to the recognized impact of atmospheric CO2 on global climate change, the study of the use of amine-oxide hybrid materials as CO2 sorbents has exploded in the past decade. While the majority of the work has concerned separation of CO2 from dilute mixtures such as flue gas from coal-fired power plants, it has been recognized by us and others that such supported amine materials are also perhaps uniquely suited to extract CO2 from ultradilute gas mixtures, such as ambient air. As unique, low temperature chemisorbents, they can operate under ambient conditions, spontaneously extracting CO2 from ambient air, while being regenerated under mild conditions using heat or the combination of heat and vacuum. This Account describes the evolution of our activities on the design of amine-functionalized silica materials for catalysis to the design, characterization, and utilization of these materials in CO2 separations. New materials developed in our laboratory, such as hyperbranched aminosilica materials, and previously known amine-oxide hybrid compositions, have been extensively studied for CO2 extraction from simulated ambient air (400 ppm of CO2). The role of amine type and structure (molecular, polymeric), support type and structure, the stability of the various compositions under simulated operating conditions, and the nature of the adsorbed CO2 have been investigated in detail. The requirements for an effective, practical air capture process have been outlined and the ability of amine-oxide hybrid materials to meet these needs has been discussed. Ultimately, the practicality of such a "direct air capture" process is predicated not only on the physicochemical properties of the sorbent, but also how the sorbent operates in a practical process that offers a scalable gas-solid contacting strategy. In this regard, the utility of low pressure drop monolith contactors is suggested to offer a practical mode of amine sorbent/air contacting for direct air capture. PMID- 26356308 TI - Identification of genes bordering breakpoints of the pericentric inversions on 2B, 4B, and 5A in bread wheat (Triticum aestivum L.). AB - Chromosome translocation is an important driving force in shaping genomes during evolution. Detailed knowledge of chromosome translocations in a given species and its close relatives should increase the efficiency and precision of chromosome engineering in crop improvement. To identify genes flanking the breakpoints of translocations and inversions as a step toward identifying breakpoints in bread wheat, we systematically analysed genes in the Brachypodium genome against wheat survey sequences and bin-mapped ESTs (expressed sequence tags) derived from the hexaploid wheat genotype 'Chinese Spring'. In addition to those well-known translocations between group 4, 5, and 7 chromosomes, this analysis identified genes flanking the three pericentric inversions on chromosomes 2B, 4B, and 5A. However, numerous chromosomal rearrangements reported in early studies could not be confirmed. The genes flanking the breakpoints reported in this study are valuable for isolating these breakpoints. PMID- 26356309 TI - AIDA-1 Moves out of the Postsynaptic Density Core under Excitatory Conditions. AB - AIDA-1 is highly enriched in postsynaptic density (PSD) fractions and is considered a major component of the PSD complex. In the present study, immunogold electron microscopy was applied to determine localization as well as the activity induced redistribution of AIDA-1 at the PSD using two antibodies that recognize two different epitopes. In cultured rat hippocampal neurons under basal conditions, immunogold label for AIDA-1 is mostly located within the dense core of the PSD, with a median distance of ~30 nm from the postsynaptic membrane. Under excitatory conditions, such as depolarization with high K+ (90 mM, 2 min) or application of NMDA (50 MUM, 2 min), AIDA-1 label density at the PSD core is reduced to 40% of controls and the median distance of label from the postsynaptic membrane increases to ~55 nm. The effect of excitatory conditions on the postsynaptic distribution of AIDA-1 is reversed within 30 minutes after returning to control conditions. The reversible removal of AIDA-1 from the PSD core under excitatory conditions is similar to the redistribution of another abundant PSD protein, SynGAP. Both SynGAP-alpha1 and AIDA-1 are known to bind PSD-95. Activity induced transient translocation of these abundant proteins from the PSD core could promote structural flexibility, vacate sites on PSD-95 for the insertion of other components and thus may create a window for synaptic modification. PMID- 26356310 TI - Low levels of hybridization between sympatric Arctic char (Salvelinus alpinus) and Dolly Varden char (Salvelinus malma) highlights their genetic distinctiveness and ecological segregation. AB - Understanding the extent of interspecific hybridization and how ecological segregation may influence hybridization requires comprehensively sampling different habitats over a range of life history stages. Arctic char (Salvelinus alpinus) and Dolly Varden (S. malma) are recently diverged salmonid fishes that come into contact in several areas of the North Pacific where they occasionally hybridize. To better quantify the degree of hybridization and ecological segregation between these taxa, we sampled over 700 fish from multiple lake (littoral and profundal) and stream sites in two large, interconnected southwestern Alaskan lakes. Individuals were genotyped at 12 microsatellite markers, and genetic admixture (Q) values generated through Bayesian-based clustering revealed hybridization levels generally lower than reported in a previous study (<0.6% to 5% of samples classified as late-generation hybrids). Dolly Varden and Arctic char tended to make different use of stream habitats with the latter apparently abandoning streams for lake habitats after 2-3 years of age. Our results support the distinct biological species status of Dolly Varden and Arctic char and suggest that ecological segregation may be an important factor limiting opportunities for hybridization and/or the ecological performance of hybrid char. PMID- 26356312 TI - Relationships Between Severity of Deformity and Impingement in Slipped Capital Femoral Epiphysis. AB - BACKGROUND: In situ pinning, a low-risk treatment for slipped capital femoral epiphysis (SCFE), leaves the slipped femoral head in place and may reduce range of motion (ROM) and cause impingement. It is unclear when a more complex surgery should be considered, because the relationships between severity, slip stability, remodeling, impingement, and ROM are unknown. RESEARCH QUESTIONS: (1) Do more severe acute SCFE deformities (no bony remodeling) result in a greater loss of flexion ROM?(2) Does the presence or location of impingement on the pelvis vary with severity of acute SCFE deformity? METHODS: We developed a 3D geometric model of acute SCFE deformity from 1 computed tomography scan of a normal adolescent hip. Ethics board approval was obtained from our institution. Bone models were created from the segmented pelvis, epiphysis, and subphyseal femur.In total, 3721 SCFE deformities were simulated by combining posterior and inferior slips in the axial and coronal planes, respectively. Southwick angles were estimated from a frog-leg lateral projection. Deformities were divided into mild (0 to 30 degrees), moderate (30 to 60 degrees), and severe (>=60 degrees) Southwick groups. Each joint was flexed in combination with internal/external rotation until contact occurred. A total of 121 ROM trials, with different degrees of internal/external rotation (0 to 90 degrees at 1.5-degree steps) were performed for each deformity. RESULTS: In total, 3355 simulated SCFE deformities (363 could not be rotated out of impingement) were analyzed.Increasing slip severity reduced flexion ROM across the range of internal/external rotation. Contact occurred for most mild deformities, and for all moderate and severe deformities in at least 1 ROM trial. Impingement was observed mainly on the anterosuperior aspect of the acetabulum. CONCLUSIONS: Increasing slip severity in acute SCFE reduced flexion and increased incidence of impingement, primarily occurring on the anterosuperior aspect of the acetabulum. The impingement patterns observed are consistent with damaged cartilage locations seen in clinical literature. CLINICAL RELEVANCE: In this experimental model, moderate and severe acute slips in SCFE lead to reduced ROM and impingement with the acetabulum. This suggests that in situ pinning may result in impingement of moderate and severe acute SCFE slips. PMID- 26356311 TI - Hotspots of Malaria Transmission in the Peruvian Amazon: Rapid Assessment through a Parasitological and Serological Survey. AB - BACKGROUND: With low and markedly seasonal malaria transmission, increasingly sensitive tools for better stratifying the risk of infection and targeting control interventions are needed. A cross-sectional survey to characterize the current malaria transmission patterns, identify hotspots, and detect recent changes using parasitological and serological measures was conducted in three sites of the Peruvian Amazon. MATERIAL AND METHODS: After full census of the study population, 651 participants were interviewed, clinically examined and had a blood sample taken for the detection of malaria parasites (microscopy and PCR) and antibodies against P. vivax (PvMSP119, PvAMA1) and P. falciparum (PfGLURP, PfAMA1) antigens by ELISA. Risk factors for malaria infection (positive PCR) and malaria exposure (seropositivity) were assessed by multivariate survey logistic regression models. Age-specific seroprevalence was analyzed using a reversible catalytic conversion model based on maximum likelihood for generating seroconversion rates (SCR, lambda). SaTScan was used to detect spatial clusters of serology-positive individuals within each site. RESULTS: The overall parasite prevalence by PCR was low, i.e. 3.9% for P. vivax and 6.7% for P. falciparum, while the seroprevalence was substantially higher, 33.6% for P. vivax and 22.0% for P. falciparum, with major differences between study sites. Age and location (site) were significantly associated with P. vivax exposure; while location, age and outdoor occupation were associated with P. falciparum exposure. P. falciparum seroprevalence curves showed a stable transmission throughout time, while for P. vivax transmission was better described by a model with two SCRs. The spatial analysis identified well-defined clusters of P. falciparum seropositive individuals in two sites, while it detected only a very small cluster of P. vivax exposure. CONCLUSION: The use of a single parasitological and serological malaria survey has proven to be an efficient and accurate method to characterize the species specific heterogeneity in malaria transmission at micro-geographical level as well as to identify recent changes in transmission. PMID- 26356313 TI - The Nature of Foot Ray Deficiency in Congenital Fibular Deficiency. AB - BACKGROUND: Absent lateral osseous structures in congenital fibular deficiency, including the distal femur and fibula, have led some authors to refer to the nature of foot ray deficiency as "lateral" as well. Others have suggested that the ray deficiency is in the central portion of the midfoot and forefoot.We sought to determine whether cuboid preservation and/or cuneiform deficiency in the feet of patients with congenital fibular deficiency implied that the ray deficiency is central rather than lateral in patients with congenital fibular deficiency. METHODS: We identified all patients with a clinical morphologic diagnosis of congenital fibular deficiency at our institution over a 15-year period. We reviewed the records and radiographs of patients who had radiographs of the feet to allow determination of the number of metatarsals, the presence or absence of a cuboid or calcaneocuboid fusion, the number of cuneiforms present (if possible), and any other osseous abnormalities of the foot. We excluded patients with 5-rayed feet, those who had not had radiographs of the feet, or whose radiographs were not adequate to allow accurate assessment of these radiographic features. We defined the characteristic "lateral (fifth) ray present" if there was a well-developed cuboid or calcaneocuboid coalition with which the lateral-most preserved metatarsal articulated. RESULTS: Twenty-six patients with 28 affected feet met radiographic criteria for inclusion in the study. All affected feet had a well-developed cuboid or calcaneocuboid coalition. The lateral-most ray of 25 patients with 26 affected feet articulated with the cuboid or calcaneocuboid coalition. One patient with bilateral fibular deficiency had bilateral partially deficient cuboids, and the lateral-most metatarsal articulated with the medial remnant of the deformed cuboids. Twenty-one of 28 feet with visible cuneiforms had 2 or 1 cuneiform. CONCLUSIONS: Although the embryology and pathogenesis of congenital fibular deficiency remain unknown, based on the radiographic features of the feet in this study, congenital fibular deficiency should not be viewed as a global "lateral lower-limb deficiency" nor the foot ray deficiency as "lateral." LEVEL OF EVIDENCE: Level IV-prognostic study. PMID- 26356314 TI - Prevalence of Discoid Meniscus During Arthroscopy for Isolated Lateral Meniscal Pathology in the Pediatric Population. AB - BACKGROUND: Meniscus tears in the young patient are becoming more prevalent. Knowledge of presenting characteristics and morphology can affect treatment decisions. The purpose of this study was to review and evaluate all the isolated lateral meniscus pathology that required arthroscopic treatment in a pediatric sports medicine practice and compare presenting characteristics between those with a discoid meniscus and those with normal meniscal morphology. METHODS: We performed a retrospective review of all isolated lateral meniscus arthroscopic procedures from 2003 to 2012 in a high-volume pediatric sports practice. Presentation, radiographs, and intraoperative findings were reviewed. The prevalence and clinical findings of a discoid meniscus in this population and among all age groups were compared with those with a meniscus tear occurring in a normal meniscus. RESULTS: Two hundred and sixty-one arthroscopies were performed for symptomatic isolated lateral menisci pathology. Of these, 75% were discoid in nature; the remainder was tears occurring in normal menisci. Ninety-six of 99 patients (97%) with lateral meniscus pathology under the age of 13 had a discoid meniscus and 66% presented with no injury. There was a transition within the population at 14 years of age, with a rise in the incidence of normal meniscal body tears. Even after this transition point, meniscal pathology incidence remained notable; 59% of isolated lateral meniscus pathology in patients between the ages of 14 and 16 years old were a discoid meniscus. Magnetic resonance imaging criteria for discoid meniscus (3 consecutive sagittal cuts or coronal mid compartment measure) were unreliable after the age of 13 years old. The ratio of complete to incomplete discoids in all age groups was 4 to 3. CONCLUSIONS: In conclusion, discoid menisci have a high prevalence in isolated lateral meniscus pathology requiring knee arthroscopy. Clinical presentation, imaging, characteristics, and treatment may be different among different age groups. In the adolescent age group (14 to 16 y old), the presentation of a discoid meniscus may not be different from a meniscus tear with normal morphology. LEVEL OF EVIDENCE: Level III-diagnostic. PMID- 26356315 TI - Determination of triacetone triperoxide with a N,N-dimethyl-p-phenylenediamine sensor on nafion using Fe3O4 magnetic nanoparticles. AB - The explosive triacetone triperoxide (TATP) can be easily manufactured from readily accessible reagents and is extremely difficult to detect, owing to the lack of UV absorbance, fluorescence, or facile ionization. The developed method is based on the acidic hydrolysis of TATP into H2O2, pH adjustment to 3.6, and the addition of magnetite nanoparticles (Fe3O4 MNPs) to the medium to produce hydroxyl radicals from H2O2, owing to the peroxidase-like activity of MNPs. The formed radicals converted the N,N-dimethyl-p-phenylenediamine (DMPD) probe to the colored DMPD(+) radical cation, the optical absorbance of which was measured at a wavelength of 554 nm. The molar absorptivity (epsilon) of the method for TATP was 21.06 * 10(3) L mol(-1) cm(-1). The colored DMPD(+) product in solution could be completely retained on a cation-exchanger Nafion membrane, constituting a colorimetric sensor for TATP and increasing the analytical sensitivity. The proposed method did not respond to a number of hand luggage items like detergent, sweetener, sugar, acetylsalicylic acid (aspirin), and paracetamol-caffeine-based analgesic drugs. On the other hand, TATP could be almost quantitatively recovered from a household detergent and sweetener that can be used as camouflage for the analyte. Neither common soil and groundwater ions (e.g., Ca(2+), Mg(2+), K(+), Cl(-), SO4(2-), and NO3(-)) at 100-fold ratios nor nitro-explosives of trinitrotoluene (TNT), hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), and pentaerythritol tetranitrate (PETN) at 10-fold amounts interfered with the proposed assay. The method was statistically validated against the standard GC/MS reference method. PMID- 26356316 TI - An empirical study of ensemble-based semi-supervised learning approaches for imbalanced splice site datasets. AB - BACKGROUND: Recent biochemical advances have led to inexpensive, time-efficient production of massive volumes of raw genomic data. Traditional machine learning approaches to genome annotation typically rely on large amounts of labeled data. The process of labeling data can be expensive, as it requires domain knowledge and expert involvement. Semi-supervised learning approaches that can make use of unlabeled data, in addition to small amounts of labeled data, can help reduce the costs associated with labeling. In this context, we focus on the problem of predicting splice sites in a genome using semi-supervised learning approaches. This is a challenging problem, due to the highly imbalanced distribution of the data, i.e., small number of splice sites as compared to the number of non-splice sites. To address this challenge, we propose to use ensembles of semi-supervised classifiers, specifically self-training and co-training classifiers. RESULTS: Our experiments on five highly imbalanced splice site datasets, with positive to negative ratios of 1-to-99, showed that the ensemble-based semi-supervised approaches represent a good choice, even when the amount of labeled data consists of less than 1% of all training data. In particular, we found that ensembles of co-training and self-training classifiers that dynamically balance the set of labeled instances during the semi-supervised iterations show improvements over the corresponding supervised ensemble baselines. CONCLUSIONS: In the presence of limited amounts of labeled data, ensemble-based semi-supervised approaches can successfully leverage the unlabeled data to enhance supervised ensembles learned from highly imbalanced data distributions. Given that such distributions are common for many biological sequence classification problems, our work can be seen as a stepping stone towards more sophisticated ensemble-based approaches to biological sequence annotation in a semi-supervised framework. PMID- 26356317 TI - A Comprehensive Analysis of the Impact of Pseudomonas aeruginosa Colonization on Prognosis in Adult Bronchiectasis. AB - RATIONALE: Eradication and suppression of Pseudomonas aeruginosa is a key priority in national guidelines for bronchiectasis and is a major focus of drug development and clinical trials. An accurate estimation of the clinical impact of P. aeruginosa in bronchiectasis is therefore essential. METHODS: Data derived from 21 observational cohort studies comparing patients with P. aeruginosa colonization with those without it were pooled by random effects meta-analysis. Data were collected for key longitudinal clinical outcomes of mortality, hospital admissions, exacerbations, and lung function decline, along with cross-sectional outcomes such as quality of life. MEASUREMENTS AND MAIN RESULTS: In the aggregate, the included studies comprised 3,683 patients. P. aeruginosa was associated with a highly significant and consistent increase in all markers of disease severity, including mortality (odds ratio [OR], 2.95; 95% confidence interval [CI], 1.98-4.40; P < 0.0001), hospital admissions (OR, 6.57; 95% CI, 3.19-13.51; P < 0.0001), and exacerbations (mean difference, 0.97/yr; 95% CI, 0.64-1.30; P < 0.0001). The patients with P. aeruginosa also had worse quality of life on the basis of their St. George's Respiratory Questionnaire results (mean difference, 18.2 points; 95% CI, 14.7-21.8; P < 0.0001). Large differences in lung function and radiological severity were also observed. The definitions of colonization were inconsistent among the studies, but the findings were robust regardless of the definition used. CONCLUSION: P. aeruginosa is associated with an approximately threefold increased risk of death and an increase in hospital admissions and exacerbations in adult bronchiectasis. PMID- 26356318 TI - Decreased Urinary Sodium-to-urinary Creatinine Ratio Identifies Sodium Depletion in Pediatric Acute Gastroenteritis. AB - In acute gastroenteritis (AG) fecal losses may cause depletion of sodium (NaD) which may not be recognized because of normal plasma Na (pNa) concentrations. We studied the incidence of this state of normonatremic sodium depletion (NNaD) and the suitability of the urinary Na/urinary creatinine ratio (uNa/uCr) for diagnosing NNaD. PATIENTS: 16 AG- and 16 healthy control children aged 0.8-15.0 years. METHODS: Prospective cross sectional pilot study. Measurements of Na, K and creatinine in plasma (p) and urine (u). Calculation of uNa/uCr Ratio, fractional excretion of Na (FENa) and uNa/uK ratio as the hitherto best known parameters of prerenal Na depletion, respectively. RESULTS: pNa concentrations were normal in 15/16 AG patients (93.8%) with only one subnormal value of 133 mmol/L, and a mean value of 137.9+/-2.3 mmol/L not different from the normal control group (139.4+/-2.2 mmol/L). Also, mean uNa concentrations and uNa/uK ratios did not differ between both groups. However, uNa/uCr ratios were below normal in 13/16 AG children (81.3%) but normal in all healthy controls with a significantly lower mean value in the AG group (12.6+/-8.8 vs. 31.2+/-8.3 mmol/mmol; p<0.0001). Similarly, 14/16 AG patients (87.5%) had a decreased FENa<0.5% with a mean FENa value significantly lower than in controls (0.36+/ 0.28% vs. 0.95+/-0.26%, p<0.0001). The good agreement between FENa and uNa/uCr results was also reflected by a high correlation coefficient of r=0.9333. CONCLUSIONS: The majority of AG patients was found to have NNaD as determined by uNa/uCr and FENa. Calculation of uNa/uCr may be useful for diagnosing NNaD in AG. PMID- 26356319 TI - Pediatric Nodular Lymphocyte-predominant Hodgkin Lymphoma: Treatment Recommendations of the GPOH-HD Study Group. AB - Nodular lymphocyte-predominant Hodgkin lymphoma (nLPHL) is a very rare disease in childhood and adolescence. In Germany, about 15 newly diagnosed patients present with this disease annually; this number comprises less than 10% of all pediatric Hodgkin lymphoma cases. Since the EuroNet-PHL-LP1 trial for early stage nLPHL patients stopped recruiting in Germany in October 2014, the GPOH-HD writing committee reviewed the literature and decided to deliver treatment recommendations for childhood and adolescent nLPHL patients. These guidelines shall be applicable to young nLPHL patients in European countries that will no longer be able to participate in nLPHL trials for young patients. Therefore, the EuroNet-PHL-nLPHL-registry will be installed to provide quality assured central review of staging and response assessment for registered patients by the Central Review Board of EuroNet-PHL in Halle/Leipzig, Germany. PMID- 26356320 TI - Kawasaki Disease Shock Syndrome (KDSS)--Presentation of 3 Children and Review of the Literature. PMID- 26356321 TI - Value of probe-based confocal laser endomicroscopy (pCLE) and dual focus narrow band imaging (dNBI) in diagnosing early squamous cell neoplasms in esophageal Lugol's voiding lesions. AB - BACKGROUND AND STUDY AIMS: Lugol's chromoendoscopy provides excellent sensitivity for the detection of early esophageal squamous cell neoplasms (ESCN), but its specificity is suboptimal. An endoscopy technique for real-time histology is required to decrease the number of unnecessary biopsies. This study aimed to compare the ESCN diagnostic capability of probed-based confocal laser endomicroscopy (pCLE) and dual focus narrow-band imaging (dNBI) in Lugol's voiding lesions. PATIENTS AND METHODS: Patients with a history of head and neck cancer without dysphagia were recruited. Lugol's voiding lesions larger than 5 mm were sequentially characterized by dNBI and pCLE by two independent operators. Finally, all lesions larger than 5 mm were biopsied followed by histological analysis, which is considered to be the gold standard in cancer diagnosis. The primary outcomes were the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and the accuracy of the two techniques. RESULTS: In total, 44 patients were enrolled with a mean age of 60 years; 80 % were male. Twenty-one Lugol's voiding lesions larger than 5 mm were detected in 12 patients. Seven lesions (33 %) from four patients were histologically diagnosed as ESCNs (four with high grade dysplasia and three with low grade dysplasia). The other 14 lesions were histologically confirmed as non-neoplastic: active esophagitis, glycogenation with inflammation, acute ulcer, inlet patch, and unremarkable changes. The sensitivity, specificity, PPV, NPV, and accuracy of pCLE vs. dNBI were 83 % vs. 85 %, 92 % vs. 62 %, 83 % vs. 54 %, 92 % vs. 89 %, and 89 % vs. 70 %, respectively (NS). CONCLUSIONS: Asymptomatic patients with a history of head and neck cancer underwent Lugol's chromoendoscopy based ESCN surveillance. Further characterization of the Lugol's voiding lesions by advanced imaging showed that both pCLE and dNBI provided good sensitivity in diagnosing ESCN, and pCLE tended to provide higher specificity, PPV, and accuracy than dNBI. Perhaps the trend of lower specificity of dNBI in this study was possibly because of the interference from Lugol's stain on the interpretation of intrapapillary capillary loops (IPCLs). Further study is required to seek a significant difference in the performance of dNBI and pCLE in a larger group of patients. PMID- 26356322 TI - Influence of He and Ar Flow Rates and NaCl Concentration on the Size Distribution of Bubbles Generated by Power Ultrasound. AB - A technique based on pulsed ultrasound and sonoluminescence emission was used to measure the size and size distribution of bubbles generated by 355 kHz power ultrasound under continuous Ar or He flow in aqueous NaCl solutions. It was observed that the bubble size strongly decreased with increasing NaCl concentration and that this decrease was much stronger than in solutions presaturated with Ar or He. This size decrease is attributed to the combination of the salting-out effect of the salt and the introduction of bubble nuclei by the continuous gas flow. Besides, the comparison of Ar and He bubbles underlines the effect of the gas diffusion coefficient on the bubble size reached. PMID- 26356323 TI - Binary Mixtures of Polycyclic Aromatic Hydrocarbons Display Nonadditive Mixture Interactions in an In Vitro Liver Cell Model. AB - Polycyclic aromatic hydrocarbons (PAHs) have been labeled contaminants of concern due to their carcinogenic potential, insufficient toxicological data, environmental ubiquity, and inconsistencies in the composition of environmental mixtures. The Environmental Protection Agency is reevaluating current methods for assessing the toxicity of PAHs, including the assumption of toxic additivity in mixtures. This study was aimed at testing mixture interactions through in vitro cell culture experimentation, and modeling the toxicity using quantitative structure-activity relationships (QSAR). Clone-9 rat liver cells were used to analyze cellular proliferation, viability, and genotoxicity of 15 PAHs in single doses and binary mixtures. Tests revealed that many mixtures have nonadditive toxicity, but display varying mixture effects depending on the mixture composition. Many mixtures displayed antagonism, similar to other published studies. QSARs were then developed using the genetic function approximation algorithm to predict toxic activity both in single PAH congeners and in binary mixtures. Effective concentrations inhibiting 50% of the cell populations were modeled, with R(2) = 0.90, 0.99, and 0.84, respectively. The QSAR mixture algorithms were then adjusted to account for the observed mixture interactions as well as the mixture composition (ratios) to assess the feasibility of QSARs for mixtures. Based on these results, toxic addition is improbable and therefore environmental PAH mixtures are likely to see nonadditive responses when complex interactions occur between components. Furthermore, QSAR may be a useful tool to help bridge these data gaps surrounding the assessment of human health risks that are associated with PAH exposures. PMID- 26356324 TI - Bioorthogonal Enzymatic Activation of Caged Compounds. AB - Engineered cytochrome P450 monooxygenase variants are reported as highly active and selective catalysts for the bioorthogonal uncaging of propargylic and benzylic ether protected substrates, including uncaging in living E. coli. observed selectivity is supported by induced-fit docking and molecular dynamics simulations. This proof-of-principle study points towards the utility of bioorthogonal enzyme/protecting group pairs for applications in the life sciences. PMID- 26356325 TI - Diabetes Mellitus Predicts Occurrence of Cirrhosis and Hepatocellular Cancer in Alcoholic Liver and Non-alcoholic Fatty Liver Diseases. AB - BACKGROUND AND AIMS: Alcohol abuse and nonalcoholic fatty liver disease (NAFLD) are common causes of liver disease. Diabetes mellitus (DM) is a common comorbidity among NAFLD patients. We performed this study with the specific aim to examine the impact of DM on progression of alcoholic liver disease (ALD) liver and NAFLD. METHODS: Medical charts of 480 patients with ALD or NAFLD (2004-2011) managed at a tertiary center were retrospectively reviewed. NAFLD was diagnosed based on exclusion of other causes of liver disease and alcohol use of <10 g/d. ALD was diagnosed based on alcohol use of >40 g/d in women or >60 g/d in men for >5 years. RESULTS: Of 480 patients (307 NAFLD), 200 diabetics differed from nondiabetics for: age (52+/-11 vs. 49+/-11 years; p=0.004); male gender (48% vs. 57%; p=0.03); metabolic syndrome (49% vs. 30%; p=0.0002); NAFLD (80% vs. 56%; p<0.0001); cirrhosis (70% vs. 59%; p=0.005); and hepatocellular carcinoma (HCC; 8% vs. 3%; p=0.009). Over a 3 year median follow-up period, diabetics relative to nondiabetics had a higher probability to develop cirrhosis (60% vs. 41%; p=0.022) and HCC (27% vs. 10%; p=0.045). There was a trend for increased development of hepatic encephalopathy in diabetics compared to nondiabetics (55% vs. 39%; p=0.053), and there was no difference between the two groups in survival or other liver disease complications. CONCLUSIONS: DM increased risk for cirrhosis and HCC among patients with ALD and NAFLD. Prospective studies with longer follow-up periods are needed to examine the impact of DM on survival and the role of aggressive HCC screening in diabetic cirrhotics. PMID- 26356326 TI - Management of Choroidal Granulomas Involving the Macula in Corticosteroid Intolerant Patients. PMID- 26356328 TI - No reflow leading to catastrophic hemodynamic collapse in a patient with severe aortic stenosis and its management. AB - We report a case of an 87-year-old female who underwent percutaneous coronary intervention (PCI) for non-ST elevation myocardial infarction while she was being worked up for transcatheter aortic valve procedure. Hemodynamic compromise occurred during the PCI, which could only be mitigated by doing a balloon aortic valvuloplasty and ImpellaTM insertion. This case report will help in preparedness for any untoward events in patients with aortic stenosis and undergoing percutaneous coronary intervention. PMID- 26356327 TI - Dual loss of the SWI/SNF complex ATPases SMARCA4/BRG1 and SMARCA2/BRM is highly sensitive and specific for small cell carcinoma of the ovary, hypercalcaemic type. AB - Small cell carcinoma of the ovary, hypercalcaemic type (SCCOHT) is a lethal and sometimes familial ovarian tumour of young women and children. We and others recently discovered that over 90% of SCCOHTs harbour inactivating mutations in the chromatin remodelling gene SMARCA4 with concomitant loss of its encoded protein SMARCA4 (BRG1), one of two mutually exclusive ATPases of the SWI/SNF chromatin remodelling complex. To determine the specificity of SMARCA4 loss for SCCOHT, we examined the expression of SMARCA4 by immunohistochemistry in more than 3000 primary gynaecological tumours. Among ovarian tumours, it was only absent in clear cell carcinoma (15 of 360, 4%). In the uterus, it was absent in endometrial stromal sarcomas (4 of 52, 8%) and high-grade endometrioid carcinomas (2 of 338, 1%). Recent studies have shown that SMARCA2 (BRM), the other mutually exclusive ATPase of the SWI/SNF complex, is necessary for survival of tumour cells lacking SMARCA4. Therefore, we examined SMARCA2 expression and discovered that all SMARCA4-negative SCCOHTs also lacked SMARCA2 protein by IHC, including the SCCOHT cell lines BIN67 and SCCOHT1. Among ovarian tumours, the SMARCA4/SMARCA2 dual loss phenotype appears completely specific for SCCOHT. SMARCA2 loss was not due to mutation but rather from an absence of mRNA expression, which was restored by treatment with the histone deacetylase inhibitor trichostatin A. Re-expression of SMARCA4 or SMARCA2 inhibited the growth of BIN67 and SCCOHT1 cell lines. Our results indicate that SMARCA4 loss, either alone or with SMARCA2, is highly sensitive and specific for SCCOHT and that restoration of either SWI/SNF ATPase can inhibit the growth of SCCOHT cell lines. PMID- 26356329 TI - Indirect photochemical transformations of acyclovir and penciclovir in aquatic environments increase ecological risk. AB - Acyclovir and penciclovir, 2 antiviral drugs, are increasingly detected in aquatic environments. The present study explores the natural photochemical transformation mechanisms and fate of these drugs, examining direct and indirect photochemical transformation under simulated sunlight irradiation. The 2 antiviral drugs are photostable under certain conditions but significantly degrade in the presence of chromophoric dissolved organic matter (DOM). The degradation rate associated with the drugs' indirect photochemical transformation scaled with chromophoric DOM concentration. Quenchers and sensitizers were used to identify indirect photochemical transformation mechanism. Results suggested that both pharmaceuticals could be transformed by reacting with (1)O2, (*)OH, and excited chromophoric DOM. The (1)O2 played an important role in indirect photochemical transformation. Furthermore, the reaction kinetics between their substructural molecules, guanine, isocytosine, and imidazole, with different reactive oxygen species were evaluated to determine which substrate functionalities were most susceptible to singlet oxygenation. Imidazole was identified as the reaction site for (1)O2, and preliminary (1)O2 oxidation mechanisms were further evaluated based on liquid chromatographic-tandem mass spectrometric results. Finally, aquatic ecotoxicity assessment of phototransformed solutions revealed that the degradation of acyclovir and penciclovir may not ultimately diminish environmental risk because of either formation of more toxic intermediates than parent pharmaceuticals or some synergistic effects existing between the intermediates. PMID- 26356330 TI - The Vital Capacity Is Vital: Epidemiology and Clinical Significance of the Restrictive Spirometry Pattern. AB - Epidemiologic research has revealed a substantial portion of the general population with abnormal spirometry results that are characterized by decreased FEV1 and FVC but a preserved FEV1/FVC ratio. This restrictive spirometry pattern (RSP) is inconsistently defined in the literature and not well addressed by current guidelines; there is an accumulating body of evidence, however, that RSP is prevalent to a similar degree as airflow obstruction. Genetic and other risk factors for RSP, such as inhalational injuries and early life exposures, continue to be actively described. Although it seems that RSP is closely associated with the metabolic syndrome, diabetes, and systemic inflammation, it is not a simple marker of obesity. RSP is associated with adverse cardiovascular outcomes, as well as mortality, and it may be an underappreciated cause of functional impairments and respiratory symptoms. Improvement in outcomes in this population will require that clinicians have an appreciation for the significance of this spirometry pattern; additional research into the clinical and radiologic phenotype of these subjects is also needed. This article provides an overview of the recent developments in our understanding of this prevalent and highly morbid spirometry pattern. PMID- 26356331 TI - Basal cell nevus syndrome: clinical and molecular review and case report. AB - Basal cell nevus syndrome (BCNS), also referred to as nevoid basal cell carcinoma syndrome or Gorlin-Goltz syndrome, was first described by Gorlin and Goltz in 1960 as an autosomal dominant disorder characterized by the early appearance of multiple basal cell carcinomas (BCCs), keratocysts of the jaw, ectopic calcifications, palmar and plantar pits, and anomalies of the ocular, skeletal, and reproductive systems. The genesis of this cancer's etiology in relation to BCNS was unclear until a few years ago when molecular analysis studies suggested a relationship between BCC and the loss-of-function mutations of the patched gene (PTCH) found on chromosome arm 9q. PTCH inhibits signaling by the membrane protein Smoothened (Smo), and this inhibition is relieved by binding sonic hedgehog (SHH) to PTCH. We describe a patient with multiple BCCs associated with x-ray anomalies of BCNS and review the basis of the SHH signaling pathway and clinical aspects of BCNS. PMID- 26356332 TI - From Function to Interaction: A New Paradigm for Accurately Predicting Protein Complexes Based on Protein-to-Protein Interaction Networks. AB - Identification of protein complexes is critical to understand complex formation and protein functions. Recent advances in high-throughput experiments have provided large data sets of protein-protein interactions (PPIs). Many approaches, based on the assumption that complexes are dense subgraphs of PPI networks (PINs in short), have been proposed to predict complexes using graph clustering methods. In this paper, we introduce a novel from-function-to-interaction paradigm for protein complex detection. As proteins perform biological functions by forming complexes, we first cluster proteins using biology process (BP) annotations from gene ontology (GO). Then, we map the resulting protein clusters onto a PPI network (PIN in short), extract connected subgraphs consisting of clustered proteins from the PPI network and expand each connected subgraph with protein nodes that have rich links to the proteins in the subgraph. Such expanded subgraphs are taken as predicted complexes. We apply the proposed method (called CPredictor) to two PPI data sets of S. cerevisiae for predicting protein complexes. Experimental results show that CPredictor outperforms the existing methods. The outstanding precision of CPredictor proves that the from-function-to interaction paradigm provides a new and effective way to computational detection of protein complexes. PMID- 26356333 TI - Beyond Fixed-Resolution Alignment-Free Measures for Mammalian Enhancers Sequence Comparison. AB - The cell-type diversity is to a large degree driven by transcription regulation, i.e., enhancers. It has been recently shown that in high-level eukaryotes enhancers rarely work alone, instead they collaborate by forming clusters of cis regulatory modules (CRMs). Even if the binding of transcription factors is sequence-specific, the identification of functionally similar enhancers is very difficult. A similarity measure to detect related regulatory sequences is crucial to understand functional correlation between two enhancers. This will allow large scale analyses, clustering and genome-wide classifications. In this paper we present Under2, a parameter-free alignment-free statistic based on variable length words. As opposed to traditional alignment-free methods, which are based on fixed-length patterns or, in other words, tied to a fixed resolution, our statistic is built upon variable-length words, and thus multiple resolutions are allowed. This will capture the great variability of lengths of CRMs. We evaluate several alignment-free statistics on simulated data and real ChIP-seq sequences. The new statistic is highly successful in discriminating functionally related enhancers and, in almost all experiments, it outperforms fixed-resolution methods. Finally, experiments on mouse enhancers show that Under2 can separate enhancers active in different tissues. AVAILABILITY: http://www.dei.unipd.it/~ciompin/main/UnderIICRMS.html. PMID- 26356334 TI - A Novel Wavelet-Based Approach for Predicting Nucleosome Positions Using DNA Structural Information. AB - Nucleosomes are basic elements of chromatin structure. The positioning of nucleosomes along a genome is very important to dictate eukaryotic DNA compaction and access. Current computational methods have focused on the analysis of nucleosome occupancy and the positioning of well-positioned nucleosomes. However, fuzzy nucleosomes require more complex configurations and are more difficult to predict their positions. We analyzed the positioning of well-positioned and fuzzy nucleosomes from a novel structural perspective, and proposed WaveNuc, a computational approach for inferring their positions based on continuous wavelet transformation. The comparative analysis demonstrates that these two kinds of nucleosomes exhibit different propeller twist structural characteristics. Well positioned nucleosomes tend to locate at sharp peaks of the propeller twist profile, whereas fuzzy nucleosomes correspond to broader peaks. The sharpness of these peaks shows that the propeller twist profile may contain nucleosome positioning information. Exploiting this knowledge, we applied WaveNuc to detect the two different kinds of peaks of the propeller twist profile along the genome. We compared the performance of our method with existing methods on real data sets. The results show that the proposed method can accurately resolve complex configurations of fuzzy nucleosomes, which leads to better performance of nucleosome positioning prediction on the whole genome. PMID- 26356335 TI - SeeSite: Characterizing Relationships between Splice Junctions and Splicing Enhancers. AB - RNA splicing is a cellular process driven by the interaction between numerous regulatory sequences and binding sites, however, such interactions have been primarily explored by laboratory methods since computational tools largely ignore the relationship between different splicing elements. Current computational methods identify either splice sites or other regulatory sequences, such as enhancers and silencers. We present a novel approach for characterizing co occurring relationships between splice site motifs and splicing enhancers. Our approach relies on an efficient algorithm for approximately solving Consensus Sequence with Outliers , an NP-complete string clustering problem. In particular, we give an algorithm for this problem that outputs near-optimal solutions in polynomial time. To our knowledge, this is the first formulation and computational attempt for detecting co-occurring sequence elements in RNA sequence data. Further, we demonstrate that SeeSite is capable of showing that certain ESEs are preferentially associated with weaker splice sites, and that there exists a co-occurrence relationship with splice site motifs. PMID- 26356336 TI - An Improved Ensemble Learning Method for Classifying High-Dimensional and Imbalanced Biomedicine Data. AB - Training classifiers on skewed data can be technically challenging tasks, especially if the data is high-dimensional simultaneously, the tasks can become more difficult. In biomedicine field, skewed data type often appears. In this study, we try to deal with this problem by combining asymmetric bagging ensemble classifier (asBagging) that has been presented in previous work and an improved random subspace (RS) generation strategy that is called feature subspace (FSS). Specifically, FSS is a novel method to promote the balance level between accuracy and diversity of base classifiers in asBagging. In view of the strong generalization capability of support vector machine (SVM), we adopt it to be base classifier. Extensive experiments on four benchmark biomedicine data sets indicate that the proposed ensemble learning method outperforms many baseline approaches in terms of Accuracy, F-measure, G-mean and AUC evaluation criterions, thus it can be regarded as an effective and efficient tool to deal with high dimensional and imbalanced biomedical data. PMID- 26356337 TI - Probabilistic Reconstruction of Ancestral Gene Orders with Insertions and Deletions. AB - Changes of gene orderings have been extensively used as a signal to reconstruct phylogenies and ancestral genomes. Inferring the gene order of an extinct species has a wide range of applications, including the potential to reveal more detailed evolutionary histories, to determine gene content and ordering, and to understand the consequences of structural changes for organismal function and species divergence. In this study, we propose a new adjacency-based method, PMAG(+) , to infer ancestral genomes under a more general model of gene evolution involving gene insertions and deletions (indels), in addition to gene rearrangements. PMAG(+) improves on our previous method PMAG by developing a new approach to infer ancestral gene contents and reducing the adjacency assembly problem to an instance of TSP. We designed a series of experiments to extensively validate PMAG(+) and compared the results with the most recent and comparable method GapAdj. According to the results, ancestral gene contents predicted by PMAG(+) coincides highly with the actual contents with error rates less than 1 percent. Under various degrees of indels, PMAG(+) consistently achieves more accurate prediction of ancestral gene orders and at the same time, produces contigs very close to the actual chromosomes. PMID- 26356338 TI - Maximum Likelihood Estimation of GEVD: Applications in Bioinformatics. AB - We propose a method, maximum likelihood estimation of generalized eigenvalue decomposition (MLGEVD) that employs a well known technique relying on the generalization of singular value decomposition (SVD). The main aim of the work is to show the tight equivalence between MLGEVD and generalized ridge regression. This relationship reveals an important mathematical property of GEVD in which the second argument act as prior information in the model. Thus we show that MLGEVD allows the incorporation of external knowledge about the quantities of interest into the estimation problem. We illustrate the importance of prior knowledge in clinical decision making/identifying differentially expressed genes with case studies for which microarray data sets with corresponding clinical/literature information are available. On all of these three case studies, MLGEVD outperformed GEVD on prediction in terms of test area under the ROC curve (test AUC). MLGEVD results in significantly improved diagnosis, prognosis and prediction of therapy response. PMID- 26356339 TI - A Simple but Powerful Heuristic Method for Accelerating k-Means Clustering of Large-Scale Data in Life Science. AB - K-means clustering has been widely used to gain insight into biological systems from large-scale life science data. To quantify the similarities among biological data sets, Pearson correlation distance and standardized Euclidean distance are used most frequently; however, optimization methods have been largely unexplored. These two distance measurements are equivalent in the sense that they yield the same k-means clustering result for identical sets of k initial centroids. Thus, an efficient algorithm used for one is applicable to the other. Several optimization methods are available for the Euclidean distance and can be used for processing the standardized Euclidean distance; however, they are not customized for this context. We instead approached the problem by studying the properties of the Pearson correlation distance, and we invented a simple but powerful heuristic method for markedly pruning unnecessary computation while retaining the final solution. Tests using real biological data sets with 50-60K vectors of dimensions 10-2001 (~400 MB in size) demonstrated marked reduction in computation time for k = 10-500 in comparison with other state-of-the-art pruning methods such as Elkan's and Hamerly's algorithms. The BoostKCP software is available at http://mlab.cb.k.u-tokyo.ac.jp/~ichikawa/boostKCP/. PMID- 26356340 TI - A High-Throughput Zebrafish Screening Method for Visual Mutants by Light-Induced Locomotor Response. AB - Normal and visually-impaired zebrafish larvae have differentiable light-induced locomotor response (LLR), which is composed of visual and non-visual components. It is recently demonstrated that differences in the acute phase of the LLR, also known as the visual motor response (VMR), can be utilized to evaluate new eye drugs. However, most of the previous studies focused on the average LLR activity of a particular genotype, which left information that could address differences in individual zebrafish development unattended. In this study, machine learning techniques were employed to distinguish not only zebrafish larvae of different genotypes, but also different batches, based on their response to light stimuli. This approach allows us to perform efficient high-throughput zebrafish screening with relatively simple preparations. Following the general machine learning framework, some discriminative features were first extracted from the behavioral data. Both unsupervised and supervised learning algorithms were implemented for the classification of zebrafish of different genotypes and batches. The accuracy of the classification in genotype was over 80 percent and could achieve up to 95 percent in some cases. The results obtained shed light on the potential of using machine learning techniques for analyzing behavioral data of zebrafish, which may enhance the reliability of high-throughput drug screening. PMID- 26356341 TI - A Novel Synthesizing Genetic Logic Circuit: Frequency Multiplier. AB - This paper presents a novel synthesizing genetic logic circuit design based on an existing synthetic genetic oscillator, which provides a function of frequency multiplier to synthesize a clock signal whose frequency is a multiple of that of the genetic oscillator. In the renowned literature, the synthetic genetic oscillator, known as a repressilator, has been successfully built in Escherichia coli to generate a periodic oscillating phenomenon through three repressive genes repress each other in a chain. On the basis of this fact, our proposed genetic frequency multiplier circuit utilizes genetic Buffers in series with a waveform shaping circuit to reshape the genetic oscillation signal into a crisp logic clock signal. By regulating different threshold levels in the Buffer, the time length of logic high/low levels in a fundamental sinusoidal wave can be engineered to pulse-width-modulated (PWM) signals with various duty cycles. Integrating some of genetic logic XOR gates and PWM signals from the output of the Buffers, a genetic frequency multiplier circuit can be created and the clock signal with the integer-fold of frequency of the genetic oscillator is generated. The synthesized signal can be used in triggering the downstream digital genetic logic circuits. Simulation results show the applicability of the proposed idea. PMID- 26356342 TI - Automatic Myonuclear Detection in Isolated Single Muscle Fibers Using Robust Ellipse Fitting and Sparse Representation. AB - Accurate and robust detection of myonuclei in isolated single muscle fibers is required to calculate myonuclear domain size. However, this task is challenging because: 1) shape and size variations of the nuclei, 2) overlapping nuclear clumps, and 3) multiple z-stack images with out-of-focus regions. In this paper, we have proposed a novel automatic detection algorithm to robustly quantify myonuclei in isolated single skeletal muscle fibers. The original z-stack images are first converted into one all-in-focus image using multi-focus image fusion. A sufficient number of ellipse fitting hypotheses are then generated from the myonuclei contour segments using heteroscedastic errors-in-variables (HEIV) regression. A set of representative training samples and a set of discriminative features are selected by a two-stage sparse model. The selected samples with representative features are utilized to train a classifier to select the best candidates. A modified inner geodesic distance based mean-shift clustering algorithm is used to produce the final nuclei detection results. The proposed method was extensively tested using 42 sets of z-stack images containing over 1,500 myonuclei. The method demonstrates excellent results that are better than current state-of-the-art approaches. PMID- 26356343 TI - Double Selection Based Semi-Supervised Clustering Ensemble for Tumor Clustering from Gene Expression Profiles. AB - Tumor clustering is one of the important techniques for tumor discovery from cancer gene expression profiles, which is useful for the diagnosis and treatment of cancer. While different algorithms have been proposed for tumor clustering, few make use of the expert's knowledge to better the performance of tumor discovery. In this paper, we first view the expert's knowledge as constraints in the process of clustering, and propose a feature selection based semi-supervised cluster ensemble framework (FS-SSCE) for tumor clustering from bio-molecular data. Compared with traditional tumor clustering approaches, the proposed framework FS-SSCE is featured by two properties: (1) The adoption of feature selection techniques to dispel the effect of noisy genes. (2) The employment of the binate constraint based K-means algorithm to take into account the effect of experts' knowledge. Then, a double selection based semi-supervised cluster ensemble framework (DS-SSCE) which not only applies the feature selection technique to perform gene selection on the gene dimension, but also selects an optimal subset of representative clustering solutions in the ensemble and improve the performance of tumor clustering using the normalized cut algorithm. DS-SSCE also introduces a confidence factor into the process of constructing the consensus matrix by considering the prior knowledge of the data set. Finally, we design a modified double selection based semi-supervised cluster ensemble framework (MDS-SSCE) which adopts multiple clustering solution selection strategies and an aggregated solution selection function to choose an optimal subset of clustering solutions. The results in the experiments on cancer gene expression profiles show that (i) FS-SSCE, DS-SSCE and MDS-SSCE are suitable for performing tumor clustering from bio-molecular data. (ii) MDS-SSCE outperforms a number of state-of-the-art tumor clustering approaches on most of the data sets. PMID- 26356344 TI - Noise Resistant Generalized Parametric Validity Index of Clustering for Gene Expression Data. AB - Validity indices have been investigated for decades. However, since there is no study of noise-resistance performance of these indices in the literature, there is no guideline for determining the best clustering in noisy data sets, especially microarray data sets. In this paper, we propose a generalized parametric validity (GPV) index which employs two tunable parameters alpha and beta to control the proportions of objects being considered to calculate the dissimilarities. The greatest advantage of the proposed GPV index is its noise resistance ability, which results from the flexibility of tuning the parameters. Several rules are set to guide the selection of parameter values. To illustrate the noise-resistance performance of the proposed index, we evaluate the GPV index for assessing five clustering algorithms in two gene expression data simulation models with different noise levels and compare the ability of determining the number of clusters with eight existing indices. We also test the GPV in three groups of real gene expression data sets. The experimental results suggest that the proposed GPV index has superior noise-resistance ability and provides fairly accurate judgements. PMID- 26356346 TI - Biomarker Signature Discovery from Mass Spectrometry Data. AB - Mass spectrometry based high throughput proteomics are used for protein analysis and clinical diagnosis. Many machine learning methods have been used to construct classifiers based on mass spectrometry data, for discrimination between cancer stages. However, the classifiers generated by machine learning such as SVM techniques typically lack biological interpretability. We present an innovative technique for automated discovery of signatures optimized to characterize various cancer stages. We validate our signature discovery algorithm on one new colorectal cancer MALDI-TOF data set, and two well-known ovarian cancer SELDI-TOF data sets. In all of these cases, our signature based classifiers performed either better or at least as well as four benchmark machine learning algorithms including SVM and KNN. Moreover, our optimized signatures automatically select smaller sets of key biomarkers than the black-boxes generated by machine learning, and are much easier to interpret. PMID- 26356345 TI - Predicting Protein Relationships to Human Pathways through a Relational Learning Approach Based on Simple Sequence Features. AB - Biological pathways are important elements of systems biology and in the past decade, an increasing number of pathway databases have been set up to document the growing understanding of complex cellular processes. Although more genome sequence data are becoming available, a large fraction of it remains functionally uncharacterized. Thus, it is important to be able to predict the mapping of poorly annotated proteins to original pathway models. RESULTS: We have developed a Relational Learning-based Extension (RLE) system to investigate pathway membership through a function prediction approach that mainly relies on combinations of simple properties attributed to each protein. RLE searches for proteins with molecular similarities to specific pathway components. Using RLE, we associated 383 uncharacterized proteins to 28 pre-defined human Reactome pathways, demonstrating relative confidence after proper evaluation. Indeed, in specific cases manual inspection of the database annotations and the related literature supported the proposed classifications. Examples of possible additional components of the Electron transport system, Telomere maintenance and Integrin cell surface interactions pathways are discussed in detail. AVAILABILITY: All the human predicted proteins in the 2009 and 2012 releases 30 and 40 of Reactome are available at http://rle.bioinfo.cnio.es. PMID- 26356347 TI - Octa-ammonium POSS-conjugated single-walled carbon nanotubes as vehicles for targeted delivery of paclitaxel. AB - BACKGROUND: Carbon nanotubes (CNTs) have unique physical and chemical properties. Furthermore, novel properties can be developed by attachment or encapsulation of functional groups. These unique properties facilitate the use of CNTs in drug delivery. We developed a new nanomedicine consisting of a nanocarrier, cell targeting molecule, and chemotherapeutic drug and assessed its efficacy in vitro. METHODS: The efficacy of a single-walled carbon nanotubes (SWCNTs)-based nanoconjugate system is assessed in the targeted delivery of paclitaxel (PTX) to cancer cells. SWCNTs were oxidized and reacted with octa-ammonium polyhedral oligomeric silsesquioxanes (octa-ammonium POSS) to render them biocompatible and water dispersable. The functionalized SWCNTs were loaded with PTX, a chemotherapeutic agent toxic to cancer cells, and Tn218 antibodies for cancer cell targeting. The nanohybrid composites were characterized with transmission electron microscopy (TEM), Fourier transform infrared (FTIR), and ultraviolet visible-near-infrared (UV-Vis-NIR). Additionally, their cytotoxic effects on Colon cancer cell (HT-29) and Breast cancer cell (MCF-7) lines were assessed in vitro. RESULTS: TEM, FTIR, and UV-Vis-NIR studies confirmed side-wall functionalization of SWCNT with COOH-groups, PTX, POSS, and antibodies. Increased cell death was observed with PTX-POSS-SWCNT, PTX-POSS-Ab-SWCNT, and free PTX compared to functionalized-SWCNT (f-SWCNT), POSS-SWCNT, and cell-only controls at 48 and 72 h time intervals in both cell lines. At all time intervals, there was no significant cell death in the POSS-SWCNT samples compared to cell-only controls. CONCLUSION: The PTX-based nanocomposites were shown to be as cytotoxic as free PTX. This important finding indicates successful release of PTX from the nanocomposites and further reiterates the potential of SWCNTs to deliver drugs directly to targeted cells and tissues. PMID- 26356348 TI - Structures of Mycobacterium tuberculosis Anthranilate Phosphoribosyltransferase Variants Reveal the Conformational Changes That Facilitate Delivery of the Substrate to the Active Site. AB - Anthranilate phosphoribosyltransferase (AnPRT) is essential for the biosynthesis of tryptophan in Mycobacterium tuberculosis (Mtb). This enzyme catalyzes the second committed step in tryptophan biosynthesis, the Mg2+-dependent reaction between 5'-phosphoribosyl-1'-pyrophosphate (PRPP) and anthranilate. The roles of residues predicted to be involved in anthranilate binding have been tested by the analysis of six Mtb-AnPRT variant proteins. Kinetic analysis showed that five of six variants were active and identified the conserved residue R193 as being crucial for both anthranilate binding and catalytic function. Crystal structures of these Mtb-AnPRT variants reveal the ability of anthranilate to bind in three sites along an extended anthranilate tunnel and expose the role of the mobile beta2-alpha6 loop in facilitating the enzyme's sequential reaction mechanism. The beta2-alpha6 loop moves sequentially between a "folded" conformation, partially occluding the anthranilate tunnel, via an "open" position to a "closed" conformation, which supports PRPP binding and allows anthranilate access via the tunnel to the active site. The return of the beta2-alpha6 loop to the "folded" conformation completes the catalytic cycle, concordantly allowing the active site to eject the product PRA and rebind anthranilate at the opening of the anthranilate tunnel for subsequent reactions. Multiple anthranilate molecules blocking the anthranilate tunnel prevent the beta2-alpha6 loop from undergoing the conformational changes required for catalysis, thus accounting for the unusual substrate inhibition of this enzyme. PMID- 26356349 TI - Mapping Local Quantum Capacitance and Charged Impurities in Graphene via Plasmonic Impedance Imaging. AB - Local quantum capacitance of graphene is imaged with plasmonics-based electrical impedance microscopy, from which the local density and polarity of charged impurities, electron and hole puddles associated with the charged impurities, and the density of the impurity states are determined. PMID- 26356350 TI - Prevalence and predictors for clinical attachment loss in adolescents in Latin America: cross-sectional study. AB - AIM: To describe the prevalence, severity and extension of clinical attachment loss (CAL) and to study the predictors in 15- to 19-year-old adolescents from high schools in the Latin America. MATERIALS AND METHODS: A cross-sectional, epidemiological study was performed. The sample included 1070 high school adolescents 15-19 years of age from Santiago de Chile (Chile), Buenos Aires, Cordoba, Mendoza (Argentina), Montevideo (Uruguay), Quito (Ecuador) and Medellin (Colombia). Calibrated examiners performed full mouth, six sites per tooth clinical examination. RESULTS: There was a response rate of 100%. The prevalence of CAL >=3 mm in >=1 site was 32.6%, probing pocket depth >=4 mm was 59.3% and bleeding on probing (BoP) >=25% was 28.6%. The logistic regression analysis adjusted for cities revealed that smoking (OR = 1.6), attending public school (OR = 2.3) and having a BoP >=25% (OR = 4.2) were positively associated with CAL >=3 mm in >= 1 site. CONCLUSION: Clinical attachment loss was prevalent in Latin America adolescents and it is associated with smoking, attendance public school and BoP. PMID- 26356351 TI - Viologen cyclophanes: redox controlled host-guest interactions. AB - Viologens can exist in three redox states varying from dicationic to neutral. This work emphasizes the control of the host-guest properties in bis-viologen cyclophanes. Two flexible cyclophanes were prepared by a cyclisation method sensitive to the odd/even number of carbons in the flexible chains linking two viologens. C5 and C7 cyclophanes were characterised by X-ray diffraction in their tetracationic state and their diradical dicationic state. In the presence of tetrathiafulvalene or methyl viologen as guests, inclusion complexes were obtained, including a mixed valence species. PMID- 26356352 TI - Platelets in cancer metastasis: To help the "villain" to do evil. AB - Cancer progress is accompanied by platelet activation and thrombotic complications. Platelets are a dangerous alliance of cancer cells, and are a close engager in multiple processes of cancer metastasis. Platelet adhesion to cancer cells forms a protective cloak that helps cancer cells to escape immune surveillance and natural killer cell-mediated cytolysis. Platelets facilitate tethering and arrest of disseminated cancer cells in the vasculature, enhance invasive potentials and thus extravasation of cancer cells. Moreover, platelets recruit monocytes and granulocytes to the sites of cancer cell arrest, and collaborate with them to establish a pro-metastatic microenvironment and metastatic niches. Platelets also secret a number of growth factors to stimulate cancer cell proliferation, release various angiogenic regulators to regulate tumor angiogenesis and subsequently promote cancer growth and progress. Albeit platelets are helping the "villain" cancer to do evil, the close engagements of platelets in cancer metastasis and progress can be used as the intervention targets for new anti-cancer therapeutic developments. Platelet-targeted anti cancer strategy may bring in novel anti-cancer treatments that can synergize the therapeutic effects of chemotherapies and surgical treatments of cancer. PMID- 26356353 TI - Spatial Resolution and Refractive Index Contrast of Resonant Photonic Crystal Surfaces for Biosensing. AB - By depositing a resolution test pattern on top of a Si3N4 photonic crystal resonant surface, we have measured the dependence of spatial resolution on refractive index contrast Deltan. Our experimental results and finite-difference time-domain (FDTD) simulations at different refractive index contrasts show that the spatial resolution of our device reduces with reduced contrast, which is an important consideration in biosensing, where the contrast may be of order 10-2. We also compare 1-D and 2-D gratings, taking into account different incidence polarizations, leading to a better understanding of the excitation and propagation of the resonant modes in these structures, as well as how this contributes to the spatial resolution. At Deltan = 0.077, we observe resolutions of 2 and 6 MUm parallel to and perpendicular to the grooves of a 1-D grating, respectively, and show that for polarized illumination of a 2-D grating, resolution remains asymmetrical. Illumination of a 2-D grating at 45 degrees results in symmetric resolution. At very low index contrast, the resolution worsens dramatically, particularly for Deltan < 0.01, where we observe a resolution exceeding 10 MUm for our device. In addition, we measure a reduction in the resonance linewidth as the index contrast becomes lower, corresponding to a longer resonant mode propagation length in the structure and contributing to the change in spatial resolution. PMID- 26356354 TI - Automixis in Artemia: solving a century-old controversy. AB - Parthenogenesis (reproduction through unfertilized eggs) encompasses a variety of reproduction modes with (automixis) or without (apomixis) meiosis. Different modes of automixis have very different genetic and evolutionary consequences but can be particularly difficult to tease apart. In this study, we propose a new method to discriminate different types of automixis from population-level genetic data. We apply this method to diploid Artemia parthenogenetica, a crustacean whose reproductive mode remains controversial despite a century of intensive cytogenetic observations. We focus on A. parthenogenetica from two western Mediterranean populations. We show that they are diploid and that markers remain heterozygous in cultures maintained up to ~36 generations in the laboratory. Moreover, parallel patterns of population-wide heterozygosity levels between the two natural populations strongly support the conclusion that diploid A. parthenogenetica reproduce by automictic parthenogenesis with central fusion and low, but nonzero recombination. This settles a century-old controversy on Artemia, and, more generally, suggests that many automictic organisms harbour steep within-chromosome gradients of heterozygosity due to a transition from clonal transmission in centromere-proximal regions to a form of inbreeding similar to self-fertilization in centromere-distal regions. Such systems therefore offer a new avenue for contrasting the genomic consequences of asexuality and inbreeding. PMID- 26356355 TI - Effect of Increased Intensity of Physiotherapy on Patient Outcomes After Stroke: An Evidence-Based Analysis. AB - BACKGROUND: After stroke, impairment of the upper and lower limb can limit patients' motor function and ability to perform activities of daily living (ADL). Physiotherapy (PT) is an established clinical practice for stroke patients, playing an important role in improving limb function. Recently, several randomized trials have evaluated the effect of higher-intensity physiotherapy (increased duration and/or frequency) on patients' functional ability. OBJECTIVES: Our objective is to investigate whether an increased intensity of PT after stroke results in better outcomes for patients. DATA SOURCES: A literature search was performed on June 7, 2013, for English-language randomized controlled trials published from January 1, 2003, to June 7, 2013. Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid Embase, EBSCO Cumulative Index to Nursing & Allied Health Literature (CINAHL), and EBM Reviews were searched. REVIEW METHODS: We reviewed the full text of articles that compared 2 or more levels of PT intensity. Outcomes of interest included motor function, ADL, and quality of life (QOL). RESULTS: High-quality evidence showed that higher intensity upper-limb PT and higher-intensity lower-limb PT both resulted in significantly greater improvements in motor function. Moderate-quality evidence showed that higher-intensity general PT did not. Moderate-quality evidence showed a significant improvement in ADL performance with higher-intensity upper-limb PT, but no improvement with higher-intensity general PT; no studies reported on ADL outcomes on lower-limb PT specifically. According to moderate-quality evidence, patient QOL did not change significantly after increased intensity of upper-limb, lower-limb, or general PT. When considering the results, one difference should be noted: Compared with the studies examining upper- and lower-limb PT, the studies examining general PT looked at a smaller increase-2 hours or less of additional therapy per week. LIMITATIONS: This analysis is limited to the earlier post stroke phase and is not equipped to comment on expected outcomes of later-stage PT. CONCLUSIONS: Overall, this analysis found support for the use of more intensive PT to improve motor function and ability to perform ADL after stroke. PMID- 26356356 TI - The prognostic value of first-trimester cystatin C levels for gestational complications. AB - AIMS: This study is designed to evaluate predictive value of first-trimester cystatin C levels for long-term pregnancy complications. METHODS: The cross sectional study population consisted of patients who admitted to outpatient clinic of a Maternity Hospital between September 2013 and December 2014. Among the 203 participants who accepted to participate in the study, 174 subjects who continued antenatal follow-up in the same clinic were included in the final analyses. Cystatin C, blood urea nitrogen, Creatinine levels and estimated glomerular filtration rates were evaluated in the first-trimester routine antenatal visit. Mode of delivery and gestational complications were noted. RESULTS: First-trimester cystatin C levels were significantly higher in cases complicated with preterm delivery and premature rupture of membrane (PROM) compared to uncomplicated ones (0.58+/-0.07 vs. 0.55+/-0.07, P=0.041, and 0.58+/ 0.07 vs. 0.55+/-0.07, P=0.036). With a cutoff value of 0.505 mg/L, sensitivity of cystatin C for preterm delivery and PROM was 91.9% and specificity was 27.7% with a negative predictive value of 92.3% and a positive predictive value of 26.6%. CONCLUSION: Detection of cystatin C levels in the first trimester of pregnancy for the prediction of preterm/PROM seems as a promising preliminary data. The relatively higher first-trimester cystatin C levels in complicated pregnancies are conspicuous. The results imply that in pregnancy cystatin C might be more than a marker for renal function. PMID- 26356357 TI - Intervention versus a conservative approach in the management of TRAP sequence: a systematic review. AB - OBJECTIVE: In the management of twin reversed arterial perfusion (TRAP) sequence, we wished to (i) determine if intervention is better than a conservative approach and (ii) assess if any of the apparent adverse prognostic indicators could guide intervention. METHODS: A systematic review was conducted between 1994 and 2014. Data extracted were inspected for heterogeneity. Overall rates and confidence intervals (CIs) for each prognostic factor were calculated. Where there were comparative data, the odds ratio (OR) was calculated. RESULTS: Twenty-six studies were included in the review. When all cases were considered, intervention either by cord occlusion or by ablation conferred a better survival rate compared with conservative management (OR=2.22, 95% CI 1.23-4.01, heterogeneity I2=37%, P=0.008). This difference was greater in the presence of one or more poor prognostic features (OR=8.58, 95% CI 1.47-49.96, heterogeneity I2=0%, P=0.02). Survival was better using ablative techniques compared to cord occlusion (OR=9.84, 95% CI 1.56-62.00, heterogeneity I2=0%, P=0.01). CONCLUSION: Intervention either by cord occlusion or by ablation confers a better survival rate compared to conservative management. This appears more compelling if there are one or more poor prognostic features. Ablative techniques are superior to cord occlusion. There were insufficient data to determine which poor prognostic features should guide management. PMID- 26356358 TI - Factors associated with participation in physical activity among adolescents in Malaysia. AB - BACKGROUND: The rising prevalence of non-communicable diseases (NCDs) has become a serious public health issue. Among the multi-factorial drivers behind NCDs are modifiable health risk factors, most notably, physical inactivity. OBJECTIVE: In response to the nearly global policy priority of encouraging regular participation in physical activity, the objective of the present study is to examine the factors that determine participation in physical activity among Malaysian adolescents. METHODS: Nationally representative data consisting of a large sample size was used. A censored regression model was developed to estimate the likelihood of participation and time spent on physical activity. RESULTS: There are significant relationships between physical activity and gender, ethnicity, self-rated academic performance, maternal education, household size and time spent on physical education. CONCLUSION: The present study provides new insights into the factors affecting physical activity participation among adolescents. Specifically, self-rated excellent academic performance, household size and physical education can increase the likelihood of being physically active. Evidence of the present study implies that policy makers should pay special attention to females, Chinese, adolescents with self-rated poor academic performance and adolescents who have low maternal education. PMID- 26356359 TI - Super-mesenteric-vein-expia-thrombosis, the clinical sequelae can be quite atrocious. AB - Superior mesenteric vein (SMV) thrombosis is a rare, potentially life-threatening complication of intra-abdominal infection. Here we present a case of massive SMV thrombosis secondary to appendicitis in a 13-year-old boy. He presented with vague abdominal pain and associated symptoms, persistently elevated serum inflammatory markers and a pyrexia of unknown origin. Sonography proved inconclusive, and a definitive diagnosis was made by abdominal contrast-enhanced computed tomography. He was treated with antibiotics and anticoagulation before interval elective laparoscopic appendectomy. The non-specific nature of the presenting symptoms makes SMV thrombosis an important differential to consider when dealing with such patients. PMID- 26356360 TI - Postnatal testosterone may be an important mediator of the association between prematurity and male neurodevelopmental disorders: a hypothesis. AB - Children born premature are at risk for neurodevelopmental disorders, including autism and schizophrenia. This piece advances the hypothesis that altered androgen exposure observed in premature infants is an important mediator of the neurodevelopmental risk in males associated with prematurity. Specifically, the alterations of normative physiologic postnatal activations of the hypothalamic pituitary-gonadal axis that occur in preterm males are hypothesized to contribute to the risk of neuropsychiatric pathology of prematurity through altered androgen mediated organizational effects on the developing brain. The physiology of testosterone and male central nervous system development in full-term births is reviewed and compared to the developmental processes of prematurity. The effects of the altered testosterone physiology observed within prematurity outside of the central nervous system are reviewed as a segue into a discussion of the effects within the nervous system, with a special focus on autism spectrum disorders and attention deficit hyperactivity disorder. The explanatory power of this model is reviewed as a supplement to the preexisting models of prematurity and neurodevelopmental risk, including infection and other perinatal central nervous system insults. The emphasis is placed on altered androgen exposure as serving as just one among many mediators of neurodevelopmental risk that may be of interest for further research and evidence-based investigation. Implications for diagnosis, management and preventative treatments conclude the piece. PMID- 26356361 TI - Evaluation of the tshr gene reveals polymorphisms associated with typical symptoms in primary congenital hypothyroidism. AB - Primary congenital hypothyroidism (PCH) has an incidence of approximately 1 in each 3000-4000 live births. In the last two decades, nearly 50 types of the distinct inactivating mutations have already been described in the coding region of the tshr gene. The aim of present study was to investigate tshr gene mutations in patients with primary congenital hypothyroidism, analyzing a sample of 106 patients that were diagnosed with PCH. Genomic DNA was isolated from peripheral blood samples, and 10 exons from the TSH receptor were automatically sequenced. Five nucleotide alterations (P52T, N187N, A459A, L645L, and D727E. N187N and D727E polymorphisms) were associated with positive medical history. In view of the clinical, biochemical and molecular heterogeneity of the etiology of the PCH, the study of polymorphisms is critical for investigating the possible associations with prevailing symptoms of this disorder. PMID- 26356362 TI - Retraction Note to the article "Up-regulation of miR-125b reverses epithelial mesenchymal transition in paclitaxel-resistant lung cancer cells. AB - No abstract available. PMID- 26356363 TI - Comparison of glenoid inclination angle using different clinical imaging modalities. AB - BACKGROUND: The beta-angle, formed by the intersection of a line on the floor of the supraspinatus fossa and glenoid fossa line, has been described as a reliable measurement tool in the clinical setting to analyze glenoid inclination on the anteroposterior (AP) view of the shoulder. The purpose of this study was to compare the accuracy of the beta-angle measurement using different imaging modalities with a validated 3-dimensional (3D) software tool. MATERIALS AND METHODS: The beta-angle was measured on AP radiographs, unformatted 2-dimensional (2D) computed tomography (CT) scan, and reformatted 2D CT scan in the scapular plane for 51 shoulders of 49 patients undergoing primary total shoulder arthroplasty. Comparison to the glenoid inclination angle calculated by the 3D software was performed. RESULTS: The beta-angle measured on reformatted CT scan was found to be the most accurate measurement method, with a mean difference of 1 degrees (standard deviation [SD], 0.5 degrees ) with respect to 3D measurement. On AP radiographs, the beta-angle was not as accurate, with a mean difference of 3 degrees (SD, 0.7 degrees ; P < .006). The beta-angle on unformatted 2D CT scan was not a reliable method to measure glenoid inclination, with a mean difference of 10 degrees (SD, 0.9 degrees ; P < .0001). CONCLUSION: The beta-angle measured with 2D CT scan formatted in the scapular plane was the most accurate method for measuring glenoid inclination. The beta-angle on the AP radiograph is less accurate and reliable. Measurement of the beta-angle on an unformatted 2D CT scan is not an acceptable method to determine glenoid inclination. PMID- 26356364 TI - Discovery, Development, and SAR of Aminothiazoles as LIMK Inhibitors with Cellular Anti-Invasive Properties. AB - As part of a program to develop a small molecule inhibitor of LIMK, a series of aminothiazole inhibitors were discovered by high throughput screening. Scaffold hopping and subsequent SAR directed development led to a series of low nanomolar inhibitors of LIMK1 and LIMK2 that also inhibited the direct biomarker p-cofilin in cells and inhibited the invasion of MDA MB-231-luc cells in a matrigel inverse invasion assay. PMID- 26356365 TI - Hearing in young adults. Part I: The effects of attitudes and beliefs toward noise, hearing loss, and hearing protector devices. AB - There is great concern regarding the development of noise-induced hearing loss (NIHL) in youth caused by high sound levels during various leisure activities. Health-orientated behavior of young adults might be linked to the beliefs and attitudes toward noise, hearing loss, and hearing protector devices (HPDs). The objective of the current study was to evaluate the effects of attitudes and beliefs toward noise, hearing loss, and HPDs on young adults' hearing status. A questionnaire and an audiological test battery were completed by 163 subjects (aged 18-30 years). The questionnaire contained the Youth Attitude to Noise Scale (YANS) and Beliefs about Hearing Protection and Hearing Loss (BAHPHL). A more positive attitude or belief represented an attitude where noise or hearing loss is seen as unproblematic and attitudes and beliefs regarding HPDs is worse. Hearing was evaluated using (high frequency) pure tone audiometry (PTA), transient evoked and distortion product otoacoustic emissions. First, mean differences in hearing between the groups with different attitudes and beliefs were evaluated using one-way analysis of variance (ANOVA). Second, a chi2 test was used to examine the usage of HPDs by the different groups with different attitudes and beliefs. Young adults with a positive attitude had significantly more deteriorated hearing and used HPDs less than the other subjects. Hearing conservation programs (HCPs) for young adults should provide information and knowledge regarding noise, hearing loss, and HPDs. Barriers wearing HPDs should especially be discussed. Further, those campaigns should focus on self experienced hearing related symptoms that might serve as triggers for attitudinal and behavioral changes. PMID- 26356366 TI - Hearing in young adults. Part II: The effects of recreational noise exposure. AB - Great concern arises from recreational noise exposure, which might lead to noise induced hearing loss in young adults. The objective of the current study was to evaluate the effects of recreational noise exposure on hearing function in young adults. A questionnaire concerning recreational noise exposures and an audiological test battery were completed by 163 subjects (aged 18-30 years). Based on the duration of exposure and self-estimated loudness of various leisure time activities, the weekly and lifetime equivalent noise exposure were calculated. Subjects were categorized in groups with low, intermediate, and high recreational noise exposure based on these values. Hearing was evaluated using audiometry, transient-evoked otoacoustic emissions (TEOAEs), and distortion product otoacoustic emissions (DPOAEs). Mean differences in hearing between groups with low, intermediate, and high recreational noise exposure were evaluated using one-way analysis of variance (ANOVA). There were no significant differences in hearing thresholds, TEOAE amplitudes, and DPOAE amplitudes between groups with low, intermediate, or high recreational noise exposure. Nevertheless, one-third of our subjects exceeded the weekly equivalent noise exposure for all activities of 75 dBA. Further, the highest equivalent sound pressure levels (SPLs) were calculated for the activities visiting nightclubs or pubs, attending concerts or festivals, and playing in a band or orchestra. Moreover, temporary tinnitus after recreational noise exposure was found in 86% of our subjects. There were no significant differences in hearing between groups with low, intermediate, and high recreational noise exposure. Nevertheless, a long-term assessment of young adults' hearing in relation to recreational noise exposure is needed. PMID- 26356367 TI - The effects of a hearing education program on recreational noise exposure, attitudes and beliefs toward noise, hearing loss, and hearing protector devices in young adults. AB - Excessive recreational noise exposure in young adults might result in noise induced hearing loss (NIHL) and tinnitus. Inducing behavioral change in young adults is one of the aims of a hearing conservation program (HCP). The goal of the current study was to evaluate the effect of a hearing education program after 6 months in young adults in relation to knowledge regarding their individual hearing status. The results of a questionnaire regarding the weekly equivalent recreational noise exposure, attitudes and beliefs toward noise, and hearing loss and hearing protector devices (HPDs) were compared between both sessions. Seventy eight young adults completed the questionnaire concerning recreational noise exposure, youth attitude to noise scale (YANS), and beliefs about hearing protection and hearing loss (BAHPHL). Their hearing status was evaluated based on admittance measures, audiometry, transient-evoked otoacoustic emissions (TEOAEs), and distortion-product otoacoustic emissions (DPOAEs). The main analysis consisted of a mixed model analysis of variance with dependent variables of either the noise exposure or the scores on (subscales of) YANS and BAHPHL. The independent variables were hearing status and session one versus session two. There was a significant decrease in recreational noise exposure and several (sub) scales of YANS and BAHPHL between both the sessions. This behavioral change resulted in a more frequent use of HPDs in 12% of the participants. However, the behavioral change was not completely related to the knowledge of young adults' individual hearing status. To prevent hearing damage in young people, investing in HCPs is necessary, apart from regulating sound levels and its compliance at various leisure-time activities. Also, the long-term effect of HCPs and their most cost-efficient repetition rates should be further investigated. PMID- 26356368 TI - DPOAE level mapping for detecting noise-induced cochlear damage from short duration music exposures. AB - Distortion product otoacoustic emission (DPOAE) level mapping provides a comprehensive picture of cochlear responses over a range of DP frequencies and f2/f1ratios. We hypothesized that individuals exposed to high-level sound would show changes detectable by DPOAE mapping, but not apparent on a standard DP-gram. Thirteen normal hearing subjects were studied before and after attending music concerts. Pure-tone audiometry (500-8,000 Hz), DP-grams (0.3-10 kHz) at 1.22 ratio, and DPOAE level maps were collected prior to, as soon as possible after, and the day after the concerts. All maps covered the range of 2,000-6,000 Hz in DP frequency and from 1.3 to -1.3 in ratio using equi-level primary tone stimuli. Changes in the pure-tone audiogram were significant (P <= 0.01) immediately after the concert at 1,000 Hz, 4,000 Hz, and 6,000 Hz. The DP-gram showed significant differences only at f2= 4,066 (P = 0.01) and f2= 4,348 (P = 0.04). The postconcert changes were readily apparent both visually and statistically (P <= 0.01) on the mean DP level maps, and remained statistically significantly different from baseline the day after noise exposure although no significant changes from baseline were seen on the DP-gram or audiogram the day after exposure. Although both the DP-gram and audiogram showed recovery by the next day, the average DPOAE level maps remained significantly different from baseline. The mapping data showed changes in the cochlea that were not detected from the DP gram obtained at a single ratio. DPOAE level mapping provides comprehensive information on subtle cochlear responses, which may offer advantages for studying and tracking noise-induced hearing loss (NIHL). PMID- 26356369 TI - Shooting history and presence of high-frequency hearing impairment in swedish hunters: A cross-sectional internet-based observational study. AB - The aim of this cross-sectional study among Swedish hunters was to examine the association between shooting history and presence of high-frequency hearing impairment (HFHI). All hunters registered with an e-mail address in the membership roster of the Swedish Hunters' Association were invited via e-mail to a secure website with a questionnaire and an Internet-based audiometry test. Associations, expressed as prevalence ratio (PR), were multivariately modelled using Poisson regression. The questionnaire was answered by 1771 hunters (age 11 91 years), and 202 of them also completed the audiometry test. Subjective severe hearing loss was reported by 195/1771 (11%), while 23/202 (11%) exhibited HFHI upon testing with Internet-based audiometry. As many as 328/1771 (19%) had never used hearing protection during hunting. In the preceding 5 years, 785/1771 (45%), had fired >6 unprotected gunshots with hunting rifle calibers. The adjusted PR of HFHI when reporting 1-6 such shots, relative to 0, was 1.5 [95% confidence interval (CI) 1.1-2.1; P = 0.02]. We could not verify any excessive HFHI prevalence among 89 hunters reporting unprotected exposure to such gunshot noise >6 times. Nor did the total number of reported rifle shots seem to matter. These findings support the notion of a wide variation in individual susceptibility to impulse noise; that significant sound energy, corresponding to unprotected noise from hunting rifle calibers, seems to be required; that susceptible individuals may sustain irreversible damage to the inner ear from just one or a few shots; and that use of hearing protection should be encouraged from the first shot with such weapons. PMID- 26356370 TI - Effects of pedagogical ideology on the perceived loudness and noise levels in preschools. AB - High activity noise levels that result in detrimental effects on speech communication have been measured in preschools. To find out if different pedagogical ideologies affect the perceived loudness and levels of noise, a questionnaire study inquiring about the experience of loudness and voice symptoms was carried out in Iceland in eight private preschools, called "Hjalli model", and in six public preschools. Noise levels were also measured in the preschools. Background variables (stress level, age, length of working career, education, smoking, and number of children per teacher) were also analyzed in order to determine how much they contributed toward voice symptoms and the experience of noisiness. Results indicate that pedagogical ideology is a significant factor for predicting noise and its consequences. Teachers in the preschool with tighter pedagogical control of discipline (the "Hjalli model") experienced lower activity noise loudness than teachers in the preschool with a more relaxed control of behavior (public preschool). Lower noise levels were also measured in the "Hjalli model" preschool and fewer "Hjalli model" teachers reported voice symptoms. Public preschool teachers experienced more stress than "Hjalli model" teachers and the stress level was, indeed, the background variable that best explained the voice symptoms and the teacher's perception of a noisy environment. Discipline, structure, and organization in the type of activity predicted the activity noise level better than the number of children in the group. Results indicate that pedagogical ideology is a significant factor for predicting self-reported noise and its consequences. PMID- 26356371 TI - Noise as an explanatory factor in work-related fatality reports. AB - Noise exposure in the workplace is a common reality in Quebec, Canada as it is elsewhere. However, the extent to which noise acts as a causal or contributive factor in industrial work-related accidents has not been studied thoroughly despite its plausibility. This article aims to describe the importance or potential importance, during investigations looking into the specific causes of each work-related fatal accident, of noise as an explanatory factor. The written information contained in the accident reports pertaining to contextual and technical elements were used. The study used multiple case qualitative content analysis. This descriptive study was based on the content analysis of the 788 reports from the Commission de la sante et de la securite du travail du Quebec [Workers' Compensation Board (WCB)] investigating the fatal work-related accidents between 1990 and 2005. The study was descriptive (number and percentages). Noise was explicitly stated as one of the explanatory factors for the fatal outcome in 2.2% (17/788) of the fatal accidents, particularly when the work involved vehicular movement or the need to communicate between workers. Noise was not typically considered a unique cause in the accident, notably because the investigators considered that the accident would have probably occurred due to other risk factors (for example, disregard of safety rules, shortcomings in work methods, and inadequate training). Noise is an important risk factor when communication is involved in work. Since noise is ubiquitous and may also interfere with vigilance and other risk factors for accidents, it may be a much more important contributing factor to accidents than is currently recognized. PMID- 26356372 TI - Otoneurological symptoms in Brazilian fishermen exposed over a long period to carbon monoxide and noise. AB - Fishing, one of the oldest productive activities, is an important sector of the Brazilian economy as well as the world economy. To evaluate the vestibular behavior in population of fishermen. It was realized as a retrospective and cross sectional study. Thirty fishermen [mean age 49.5 (+/- 8.5) years] whose age ranged from 33 years to 67 years were submitted to anamnesis, otorhinolaryngological evaluation, and vestibular examination through the electronystagmography (ENG). The most evident otoneurological symptoms were: Tinnitus (66.7%), dizziness (63.3%), and hearing loss (53.3%). The most evident clinical symptoms were: Fatigue (36.7%), anxiety (23.3%), and depression (16.7%). There were alterations in the vestibular examination of 13 (43.3%) fishermen in the caloric test. There was a prevalence of alteration in the peripheral vestibular system and there was a major frequency of the peripheral vestibular irritative syndrome (30.0%). CONCLUSION: The otoneurological complaints were frequent in the population studied that verifies the importance of allowing labyrinth examinations and the need for adopting preventive measures related to noise exposure to carbon monoxide (CO), since they can cause and/enhance various manifestations of labyrinthine vestibular impairment that can affect the quality of life of these workers. PMID- 26356373 TI - Road, rail, and air transportation noise in residential and workplace neighborhoods and blood pressure (RECORD Study). AB - Associations between road traffic noise and hypertension have been repeatedly documented, whereas associations with rail or total road, rail, and air (RRA) traffic noise have rarely been investigated. Moreover, most studies of noise in the environment have only taken into account the residential neighborhood. Finally, few studies have taken into account individual/neighborhood confounders in the relationship between noise and hypertension. We performed adjusted multilevel regression analyses using data from the 7,290 participants of the RECORD Study to investigate the associations of outdoor road, rail, air, and RRA traffic noise estimated at the place of residence, at the workplace, and in the neighborhoods around the residence and workplace with systolic blood pressure (SBP), diastolic blood pressure (DBP), and hypertension. Associations were documented between higher outdoor RRA and road traffic noise estimated at the workplace and a higher SBP [+1.36 mm of mercury, 95% confidence interval (CI): +0.12, +2.60 for 65-80 dB(A) vs 30-45 dB(A)] and DBP [+1.07 (95% CI: +0.28, +1.86)], after adjustment for individual/neighborhood confounders. These associations remained after adjustment for risk factors of hypertension. Associations were documented neither with rail traffic noise nor for hypertension. Associations between transportation noise at the workplace and blood pressure (BP) may be attributable to the higher levels of road traffic noise at the workplace than at the residence. To better understand why only noise estimated at the workplace was associated with BP, our future work will combine Global Positioning System (GPS) tracking, assessment of noise levels with sensors, and ambulatory monitoring of BP. PMID- 26356374 TI - Noise exposure and cognitive performance: A study on personnel on board Royal Norwegian Navy vessels. AB - Prior research shows that work on board vessels of the Royal Norwegian Navy (RNoN) is associated with noise exposure levels above recommended standards. Further, noise exposure has been found to impair cognitive performance in environmental, occupational, and experimental settings, although prior research in naval and maritime settings is sparse. The aim of this study was to evaluate cognitive performance after exposure to noise among personnel working on board vessels in the RNoN. Altogether 87 Navy personnel (80 men, 7 women; 31 +/- 9 years) from 24 RNoN vessels were included. Noise exposure was recorded by personal noise dosimeters at a minimum of 4 h prior to testing, and categorized into 4 groups for the analysis: <72.6 dB(A), 72.6-77.0 dB(A), 77.1-85.2 dB(A), and >85.2 dB(A). The participants performed a visual attention test based on the Posner cue-target paradigm. Multivariable general linear model (GLM) analyses were performed to analyze whether noise exposure was associated with response time (RT) when adjusting for the covariates age, alertness, workload, noise exposure in test location, sleep the night before testing, use of hearing protection device (HPD), and percentage of errors. When adjusting for covariates, RT was significantly increased among personnel exposed to >85.2 dB(A) and 77.1 85.2 dB(A) compared to personnel exposed to <72.6 dB(A). PMID- 26356375 TI - Does exposure to aircraft noise increase the mortality from cardiovascular disease in the population living in the vicinity of airports? Results of an ecological study in France. AB - The impact of aircraft noise on health is of growing concern. We investigated the relationship between this exposure and mortality from cardiovascular disease, coronary heart disease, myocardial infarction, and stroke. We performed an ecological study on 161 communes (commune being the smallest administrative unit in France) close to the following three major French airports: Paris-Charles de Gaulle, Lyon Saint-Exupery, and Toulouse-Blagnac. The mortality data were provided by the French Center on Medical Causes of Death for the period 2007 2010. Based on the data provided by the French Civil Aviation Authority, a weighted average exposure to aircraft noise (L den AEI) was computed at the commune level. A Poisson regression model with commune-specific random intercepts, adjusted for potential confounding factors including air pollution, was used to investigate the association between mortality rates and L den AEI. Positive associations were observed between L den AEI and mortality from cardiovascular disease [adjusted mortality rate ratio (MRR) per 10 dB(A) increase in L den AEI = 1.18; 95% confidence interval (CI): 1.11-1.25], coronary heart disease [MRR = 1.24 (1.12-1.36)], and myocardial infarction [MRR = 1.28 (1.11 1.46]. Stroke mortality was more weakly associated with L den AEI [MRR = 1.08 (0.97-1.21]. These significant associations were not attenuated after the adjustment for air pollution. The present ecological study supports the hypothesis of an association between aircraft noise exposure and mortality from cardiovascular disease, coronary heart disease, and myocardial infarction. However, the potential for ecological bias and the possibility that this association could be due to residual confounding cannot be excluded. PMID- 26356376 TI - Human amygdala activation by the sound produced during dental treatment: A fMRI study. AB - During dental treatments, patients may experience negative emotions associated with the procedure. This study was conducted with the aim of using functional magnetic resonance imaging (fMRI) to visualize cerebral cortical stimulation among dental patients in response to auditory stimuli produced by ultrasonic scaling and power suction equipment. Subjects (n = 7) aged 23-35 years were recruited for this study. All were right-handed and underwent clinical pure-tone audiometry testing to reveal a normal hearing threshold below 20 dB hearing level (HL). As part of the study, subjects initially underwent a dental calculus removal treatment. During the treatment, subjects were exposed to ultrasonic auditory stimuli originating from the scaling handpiece and salivary suction instruments. After dental treatment, subjects were imaged with fMRI while being exposed to recordings of the noise from the same dental instrument so that cerebral cortical stimulation in response to aversive auditory stimulation could be observed. The independent sample confirmatory t-test was used. Subjects also showed stimulation in the amygdala and prefrontal cortex, indicating that the ultrasonic auditory stimuli elicited an unpleasant response in the subjects. Patients experienced unpleasant sensations caused by contact stimuli in the treatment procedure. In addition, this study has demonstrated that aversive auditory stimuli such as sounds from the ultrasonic scaling handpiece also cause aversive emotions. This study was indicated by observed stimulation of the auditory cortex as well as the amygdala, indicating that noise from the ultrasonic scaling handpiece was perceived as an aversive auditory stimulus by the subjects. Subjects can experience unpleasant sensations caused by the sounds from the ultrasonic scaling handpiece based on their auditory stimuli. PMID- 26356377 TI - Predictive factors of occupational noise-induced hearing loss in Spanish workers: A prospective study. AB - The purpose of our study was to identify the main factors associated with objective noise-induced hearing loss (NIHL), as indicated by abnormal audiometric testing, in Spanish workers exposed to occupational noise in the construction industry. We carried out a prospective study in Tenerife, Spain, using 150 employees exposed to occupational noise and 150 age-matched controls who were not working in noisy environments. The variables analyzed included sociodemographic data, noise-related factors, types of hearing protection, self-report hearing loss, and auditory-related symptoms (e.g., tinnitus, vertigo). Workers with pathological audiograms had significantly longer noise-exposure duration (16.2 +/ 11.4 years) relative to those with normal audiograms (10.2 +/- 7.0 years; t = 3.99, P < 0.001). The vast majority of those who never used hearing protection measures had audiometric abnormalities (94.1%). Additionally, workers using at least one of the protection devices (earplugs or earmuffs) had significantly more audiometric abnormalities than those using both protection measures simultaneously (Chi square = 16.07; P < 0.001). The logistic regression analysis indicates that the use of hearing protection measures [odds ratio (OR) = 12.30, confidence interval (CI) = 4.36-13.81, P < 0.001], and noise-exposure duration (OR = 1.35, CI = 1.08-1.99, P = 0.040) are significant predictors of NIHL. This regression model correctly predicted 78.2% of individuals with pathological audiograms. The combined use of hearing protection measures, in particular earplugs and earmuffs, associates with a lower rate of audiometric abnormalities in subjects with high occupational noise exposure. The use of hearing protection measures at work and noise-exposure duration are best predictive factors of NIHL. Auditory-related symptoms and self-report hearing loss do not represent good indicators of objective NIHL. Routine monitoring of noise levels and hearing status are of great importance as part of effective hearing conservation programs. PMID- 26356378 TI - The association of noise sensitivity with music listening, training, and aptitude. AB - After intensive, long-term musical training, the auditory system of a musician is specifically tuned to perceive musical sounds. We wished to find out whether a musician's auditory system also develops increased sensitivity to any sound of everyday life, experiencing them as noise. For this purpose, an online survey, including questionnaires on noise sensitivity, musical background, and listening tests for assessing musical aptitude, was administered to 197 participants in Finland and Italy. Subjective noise sensitivity (assessed with the Weinstein's Noise Sensitivity Scale) was analyzed for associations with musicianship, musical aptitude, weekly time spent listening to music, and the importance of music in each person's life (or music importance). Subjects were divided into three groups according to their musical expertise: Nonmusicians (N = 103), amateur musicians (N = 44), and professional musicians (N = 50). The results showed that noise sensitivity did not depend on musical expertise or performance on musicality tests or the amount of active (attentive) listening to music. In contrast, it was associated with daily passive listening to music, so that individuals with higher noise sensitivity spent less time in passive (background) listening to music than those with lower sensitivity to noise. Furthermore, noise-sensitive respondents rated music as less important in their life than did individuals with lower sensitivity to noise. The results demonstrate that the special sensitivity of the auditory system derived from musical training does not lead to increased irritability from unwanted sounds. However, the disposition to tolerate contingent musical backgrounds in everyday life depends on the individual's noise sensitivity. PMID- 26356379 TI - Pure tone hearing thresholds and leisure noise: Is there a relationship? AB - This paper reports on the examination of the relationship between self-reported historical noise exposure during leisure activities and audiological indicators: Measured hearing threshold levels (HTLs) and otoacoustic emissions (OAEs). The research was conducted by a cross-sectional survey of 1,432 individuals whose ages ranged from 11 years to 35 years. Methodology included a comprehensive audiometric assessment including otoscopy, pure tone audiometry (PTA) (air- and bone-conduction), OAEs, and tympanometry. A comprehensive questionnaire gathered information on demographics, hearing health status, and participation in work, non-work, and leisure activities. Using the history of work, non-work, and leisure noise exposure, a cumulative lifetime noise exposure was estimated. No correlation was found between cumulative lifetime noise exposure and audiometric PTA or OAE parameters. PMID- 26356380 TI - Measurement of impulse peak insertion loss from two acoustic test fixtures and four hearing protector conditions with an acoustic shock tube. AB - Impulse peak insertion loss (IPIL) was studied with two acoustic test fixtures and four hearing protector conditions at the E-A-RCAL Laboratory. IPIL is the difference between the maximum estimated pressure for the open-ear condition and the maximum pressure measured when a hearing protector is placed on an acoustic test fixture (ATF). Two models of an ATF manufactured by the French-German Research Institute of Saint-Louis (ISL) were evaluated with high-level acoustic impulses created by an acoustic shock tube at levels of 134 decibels (dB), 150 dB, and 168 dB. The fixtures were identical except that the E-A-RCAL ISL fixture had ear canals that were 3 mm longer than the National Institute for Occupational Safety and Health (NIOSH) ISL fixture. Four hearing protection conditions were tested: Combat Arms earplug with the valve open, ETYPlugs (r) earplug, TacticalPro headset, and a dual-protector ETYPlugs earplug with TacticalPro earmuff. The IPILs measured for the E-A-RCAL fixture were 1.4 dB greater than the National Institute for Occupational Safety and Health (NIOSH) ISL ATF. For the E A-RCAL ISL ATF, the left ear IPIL was 2.0 dB greater than the right ear IPIL. For the NIOSH ATF, the right ear IPIL was 0.3 dB greater than the left ear IPIL. PMID- 26356381 TI - The influence of tinnitus acceptance on the quality of life and psychological distress in patients with chronic tinnitus. AB - Recent findings show the importance of acceptance in the treatment of chronic tinnitus. So far, very limited research investigating the different levels of tinnitus acceptance has been conducted. The aim of this study was to investigate the quality of life (QoL) and psychological distress in patients with chronic tinnitus who reported different levels of tinnitus acceptance. The sample consisted of outpatients taking part in a tinnitus coping group (n = 97). Correlations between tinnitus acceptance, psychological distress, and QoL were calculated. Receiver operating characteristic (ROC) curves were used to calculate a cutoff score for the German "Tinnitus Acceptance Questionnaire" (CTAQ-G) and to evaluate the screening abilities of the CTAQ-G. Independent sample t-tests were conducted to compare QoL and psychological distress in patients with low tinnitus acceptance and high tinnitus acceptance. A cutoff point for CTAQ-G of 62.5 was defined, differentiating between patients with "low-to-mild tinnitus acceptance" and "moderate-to-high tinnitus acceptance." Patients with higher levels of tinnitus acceptance reported a significantly higher QoL and lower psychological distress. Tinnitus acceptance plays an important role for patients with chronic tinnitus. Increased levels of acceptance are related to better QoL and less psychological distress. PMID- 26356382 TI - Comment on "Elucidating the relationship between noise sensitivity and personality" by Shepherd et al. PMID- 26356383 TI - Concerns with amplitude variation in calibrated audiometer systems in clinical simulations. PMID- 26356384 TI - Intrasession and Intersession Reliability of Running Mechanics During Treadmill Sprints. AB - PURPOSE: To determine the intrasession and intersession (ie, within- and between days) reliability in treadmill sprinting-performance outcomes and associated running mechanics. METHODS: After familiarization, 13 male recreational sportsmen (team- and racket-sport background) performed three 5-s sprints on an instrumented treadmill with 2 min recovery on 3 different days, 5-7 d apart. Intrasession (comparison of the 3 sprints of the first session) and intersession (comparison of the average of the 3 sprints across days) reliability of performance, kinetics, kinematics, and spring-mass variables were assessed by intraclass correlation coefficient (ICC) and coefficients of variation (CV%). RESULTS: Intrasession reliability was high (ICC > .94 and CV < 8%). Intersession reliability was good for performance indices (.83 < ICC < .89 and CV < 10%, yet with larger variability for mean velocity than for distance covered or propulsive power) and kinetic parameters (ICC > .94 and CV < 5%, yet with larger variability for mean horizontal forces than for mean vertical forces) and ranged from good to high for all kinematic (.88 < ICC < .95 and CV <= 3.5%) and spring-mass variables (.86 < ICC < .99 and CV <= 6.5%). Compared with intrasession, minimal detectable differences were on average twice larger for intersession designs, except for sprint kinetics. CONCLUSION: Instrumented treadmill sprint offers a reliable method of assessing running mechanics during single sprints either within the same session or between days. PMID- 26356385 TI - Effects of fast and slow squat exercises on the muscle activity of the paretic lower extremity in patients with chronic stroke. AB - [Purpose] The purpose of this study was to investigate the effects of the speed of squat exercises on paretic lower extremity muscle activity in patients with hemiplegia following a stroke. [Subjects and Methods] Ten stroke patients performed fast and slow squat exercises for 2 seconds and 8 seconds, respectively. The muscle activities of the paretic and non-paretic sides of the rectus femoris muscle, the biceps femoris muscle, and the tibialis anterior muscle were assessed and compared using surface electromyography. [Results] The paretic side of the rectus femoris muscle showed statistically significant differences in the fast squat exercise group, which demonstrated the highest muscle activity during the rapid return to the upright position. [Conclusion] The rectus femoris muscle showed the highest muscle activity during the return to the upright position during the fast squat exercise, which indicates that the rectus femoris muscle is highly active during the fast squat exercise. PMID- 26356386 TI - The emergence of copper(I)-based dye sensitized solar cells. AB - Since the discovery of Gratzel-type dye sensitized solar cells (DSCs) in the early 1990s, there has been an exponential growth in the number of publications dealing with their optimization and new design concepts. Conventional Gratzel DSCs use ruthenium(II) complexes as sensitizers, and the highest photon-to electrical current conversion efficiency for a ruthenium dye is ~12%. However, ruthenium is both rare and expensive, and replacement by cheaper and more sustainable metals is desirable. In this Tutorial Review, we describe strategies for assembling copper(I) complexes for use as dyes in DSCs, a research area that has been active since ~2008. We demonstrate design principles for (I) ligands to anchor the complex to a semiconductor surface and promote electron transfer from dye to semiconductor, and (II) ancillary ligands to tune the light absorption properties of the dye and facilitate electron transfer from electrolyte to dye in the DSC. We assess the progress made in terms of light-harvesting and overall photoconversion efficiencies of copper(I)-containing DSCs and highlight areas that remain ripe for development and improvement. PMID- 26356387 TI - Bioconcentration, metabolism and alterations of thyroid hormones of Tris(1,3 dichloro-2-propyl) phosphate (TDCPP) in Zebrafish. AB - Tris(1,3-dichloro-2-propyl) phosphate (TDCPP) is an organophosphate widely used as a flame retardant, and has frequently been detected in the environment and biota. The present study investigates the bioconcentration and metabolism of TDCPP in fish. Zebrafish embryos (from 2h post-fertilization) were exposed to TDCPP (0, 4, 20 and 100MUg/L) for six months. Exposure to TDCPP significantly induced phase I metabolic enzymes 7-ethoxyresorufin O-deethylase (EROD) and 7 methoxyresorufin O-demethylase (MROD) in fish. The mRNA expression of genes related to Phase I and II metabolic enzymes, such as cyp1a1, cyp1b1, cyp1c1 and ugt1ab were also significantly upregulated. Exposure to TDCPP significantly reduced plasma thyroxine (T4) and 3,5,3'-triiodothyronine (T3) levels in females. Chemicals analysis indicated significant levels of TDCPP and its metabolite, bis (1,3-dichloro-2-propyl) phosphate (BDCPP), in the liver. The present study reveals that exposure to low concentrations of TDCPP can cause bioconcentration in fish, and TDCPP can be readily metabolized in liver. PMID- 26356388 TI - Effect of enrofloxacin and chlorpyrifos on the levels of vitamins A and E in Wistar rats. AB - This study investigates the effects of enrofloxacin and chlorpyrifos, and their combination on vitamin A and E concentrations in the liver of rats. Results of this study indicated a reduction in the contents of vitamins A and E in the liver, which persisted for the entire period of the experiment. Vitamins A and E concentrations were slightly decreased (2-7%) in enrofloxacin-treated rats. In the group of rats intoxicated with chlorpyrifos, a significant decrease in the level of vitamin A was observed up to the 24th hour, and for vitamin E up to the 3rd day from the discontinuation of intoxication with the compounds under study. In the enrofloxacin-chlorpyrifos co-exposure group reduced vitamins A and E level was also noted. The greatest fall in vitamin A level was observed after 3h, while the contents of vitamin E decreased progressively up to the 3rd day. Changes in this group were less pronounced in comparison to the animals intoxicated with chlorpyrifos only. PMID- 26356389 TI - Proteomic identification of mitochondrial targets involved in andrographolide sodium bisulfite-induced nephrotoxicity in a rat model. AB - Our previous works have indicated that the mitochondrion is the primary target of nephrotoxicity induced by andrographolide sodium bisulfate (ASB), but the mechanisms of ASB-induced nephrotoxicity have remained largely unknown. In this study, proteomic analysis was used to explore the changes in the renal mitochondrial proteome in SD rats after treatment with ASB. SD rats were intraperitoneally administered with ASB (100, 600mg/kg/d) for 7 days. Renal impairment was evaluated by pathological observation. Two-dimensional gel electrophoresis (2-DE), as well as matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS), was applied for the identification of mitochondrial protein and was validated by Western blotting. Protein-protein interactions were analyzed using a Web-based bioinformatics tool (STRING, version 9.1). Rat kidneys exhibited histopathological changes after treatment with ASB, and 13 proteins were significantly changed, including ES1 protein homolog, heat shock cognate 71kDa protein, peroxiredoxin-1 (Prdx1), cytochrome C oxidase subunit 5B (COX5B), prohibitin (PHB), threonine-tRNA ligase, pyruvate dehydrogenase E1 component subunit beta (PDH-beta), voltage-dependent anion-selective channel protein 2 (VDAC2), voltage-dependent anion-selective channel protein 1 (VDAC1), adenylate kinase 2 (KAD2) and others. These data demonstrated that the expression levels of several proteins significantly changed in the mitochondria, and these proteins could be candidate biomarkers for ASB induced nephrotoxicity. PMID- 26356390 TI - Effects of acute exposure to WIFI signals (2.45GHz) on heart variability and blood pressure in Albinos rabbit. AB - Electrocardiogram and arterial pressure measurements were studied under acute exposures to WIFI (2.45GHz) during one hour in adult male rabbits. Antennas of WIFI were placed at 25cm at the right side near the heart. Acute exposure of rabbits to WIFI increased heart frequency (+22%) and arterial blood pressure (+14%). Moreover, analysis of ECG revealed that WIFI induced a combined increase of PR and QT intervals. By contrast, the same exposure failed to alter maximum amplitude and P waves. After intravenously injection of dopamine (0.50ml/kg) and epinephrine (0.50ml/kg) under acute exposure to RF we found that, WIFI alter catecholamines (dopamine, epinephrine) action on heart variability and blood pressure compared to control. These results suggest for the first time, as far as we know, that exposure to WIFI affect heart rhythm, blood pressure, and catecholamines efficacy on cardiovascular system; indicating that radiofrequency can act directly and/or indirectly on cardiovascular system. PMID- 26356391 TI - [Identification of people at the latent stage of Parkinson's disease (the PARKINLAR study): first results and an optimization of the algorithm]. AB - AIM: To work out an optimal algorithm to identify people at the latent stage of neurodegenerative process of "parkinsonian" type in the Russian population. MATERIAL AND METHODS: Authors launched a two-step study aimed at identifying people at the latent stage of Parkinson's disease (PD) in the Russian population the PARKINLAR (PARKINsonism, LAtent stage, Russia). As the first step, we formed a group of "primary risk" by the identification in neurologically healthy people of at least one of the following confirmed PD risk factors: a) the substantia nigra hyperechogenicity (ultrasound screening was performed in 193 people); b) mutations in "parkinsonian" genes (genetic screening was performed in 29 relatives of PD patients from families with LRRK2, PARK2 and GBA mutations). Thereby, 37 people comprised the "primary risk" group, of whom 23 agreed to continue further examination (44+/-10.2 years). A matched group of people without the aforementioned primary biomarkers of PD served as control. As the second step, we undertook in the prescreened groups a complex of investigations assessing the presence of secondary ("minor") biomarkers of PD: Sniffin' Sticks olfactory testing; color visual evoked potentials; analysis of goal-directed eye head-hand movements with the use of a special neuro-cybernetic system; assessment of motor and non-motor symptoms with the use of UPDRS and NMSS scales. RESULTS: When comparing the "primary risk" group with controls, maximal differences in the occurrence of symptoms were seen for goal-directed eye movements (43.5% vs. 20.0%) and color vision (39.1% vs. 26.7%). Among these individuals, we found two people with 4 secondary biomarkers and one with 3, and no such observations in controls. People with the combination of a primary biomarker with several secondary biomarkers of PD comprised a group of "high risk" in our study. CONCLUSION: Optimization of this algorithm of population screening of people predisposed to the development of PD may be done by expanding the spectrum of biomarkers and assessing their validity in a long-term prospective observational study. PMID- 26356392 TI - [A comparative hormonal and clinical analysis of thyrotoxicosis with- or without comorbid resistant depression]. AB - AIM: To compare clinical and hormonal status in thyrotoxicosis with- or without comorbid resistant depression. MATERIAL AND METHODS: We examined 100 patients with thyrotoxicosis, including 61 patients with comorbid resistant depression (RD) and 39 patients without RD. Mental status, somatic symptoms of disease and blood content of main thyroid hormones were studied. The Hamilton scale was used to measure depression and anxiety. RESULTS AND CONCLUSION: Depression developed in the structure of thyrotoxicosis increased the symptoms of hyperthyroidism. However, it did not change the general tendency of development of the main disease assessed by hormonal indicators. PMID- 26356393 TI - [An experience of using divasa in the treatment of cerebrovascular insufficiency]. AB - AIM: To evaluate the clinical efficacy and safety of divasa in the treatment of patients with cerebrovascular insufficiency. MATERIAL AND METHODS: The main group included 40 patients (mean age 56.2+/-5.7 years) with asthenic/autonomic and vestibular/ataxic disorders developed during chronic cerebrovascular disease. The severity of symptoms was measured with the Visual Analogue scale (VAS). Neuropsychological and psychoemotional status was assessed with MMSE, MFI-20, HAM A, a subjective sleep questionnaire, a scheme for detection of signs of autonomic disorders. Quality of life questionnaire (SF-36) and CGI scale were used as well. The plasma levels of fibrinogen and the von Willebrand factor were determined in all patients. The control group included 40 patients with chronic cerebrovascular insufficiency matched for age, sex and severity of neurological symptoms to the main group. RESULTS: The scores of asthenic symptoms, anxiety, sleep disorders and autonomic disorders were decreased significantly that led to the improvement of quality of life of patients. A significant decrease and normalization of the plasma levels of fibrinogen and the von Willebrand factor were identified in the patients of the main group. The drug was well-tolerated, side-effects (allergic reactions) were noted only in 5%. CONCLUSION: The positive effect of divasa on patient's condition was demonstrated. The drug may be recommended for the use in complex treatment of these patients. PMID- 26356394 TI - [Optimization of the efficacy and safety of antidepressant therapy in patients of a geriatric psychiatric unit]. AB - AIM: A comparative evaluation of the efficacy and safety of monotherapy with one of the modern antidepressants (venlafaxine, agomelatine, or fluvoxamine) and combination treatment of one of the above mentioned antidepressants with acetyl-L carnitine (ALS, carnicetine) in the geriatric psychiatric unit. MATERIAL AND METHODS: Two groups of elderly patients (aged 60-79 years) with mild or moderate depression, randomized according to a number of demographic and clinical characteristics, were treated with antidepressants in monotherapy or combined therapy (antidepressant/carnicetine) within 8 weeks. RESULTS: Combination therapy with the neurotrophic agent carnicetine proved to be more effective compared to monotherapy. At the end of treatment, the more rapid clinical response has been shown for depression, anxiety, apathy, and cognitive dysfunction. Furthermore, combination therapy provides less adverse effects. CONCLUSION: Antidepressant/carnicetine combination therapy may be recommended for treatment of depression in elderly patients. PMID- 26356395 TI - [Optimization of the treatment of anxiety disorders with selank]. AB - AIM: To compare the efficacy and tolerability of monotherapy with phenazepam to complex treatment with the peptide preparation selank and phenazepam in patients with anxiety disorders. MATERIAL AND METHODS: Authors explored the anxiolytic effect and tolerability of monotherapy with phenazepam (30 patients) and complex treatment with selank and phenazepam (40 patients) in anxiety-phobic, hypochondriac and somatoform disorders (ICD-10 items F40.2-9, F41.1-9, F45.0-2). Therapeutic effect was assessed clinically and with HDRS, CGI and Spilberger scales. Tolerability was evaluated using the UKU scale. Stroop test and verbal fluency test were used. Quality of life was assessed with the SF-36. RESULTS: The positive effect of phenazepam was achieved earlier in the optimization of treatment with selank on HDRS. The combined treatment decreased the level of undesirable side-effects of phenazepam (attention and memory impairment, asthenia, sedation, increase in sleep duration, sexual disturbances, emotional indifference and orthostatism) during the course of treatment and after the tranquilizer withdrawal. Taken together, the therapeutic efficacy and reduction of side-effects had a positive impact on the quality-of-life of the patients treated with selank as add-on to phenazepam. CONCLUSION: The results extend therapeutic possibilities of treatment of anxietyspectrum disorders with the combination of benzodiazepine tranquilizers and selank. PMID- 26356396 TI - [Ways to optimize the treatment of patients with discogenic-venous lumbosacral radiculomyeloischemia]. AB - AIM: Treatment of patients with neurological manifestations of degenerative dystrophic lesions of the spine must be integrated and optimized from the perspective of pathogenesis. Antiedematous therapy is an important moment that takes into account the development of localized swelling affected the spinal structures. We studied the efficacy of L-lysine aescinat in the treatment of patients with discogenic-venous lumbosacral radiculomyelopathy. MATERIAL AND METHODS: We analyzed the therapeutic efficacy of antitumor therapy with the drug L-lysine aescinat in 40 patients with discogenic-venous lumbosacral radiculomyelopathy in comparison with a control group of 40 patients treated with conventional therapy in a neurological hospital. The age of the patients ranged from 30 to 60 years. In total, there were 36 (45 %) women and 44 (55%) men. Herniated discs were visualized by MRI in all patients, attention was drawn to the condition of radicular veins of the cauda equina. We assessed muscle strength of lumbosacral myotomes, their trophicity and state of segmental-conductor apparatus sensitivity with the quantitative determination of the time of vibration of a tuning fork. RESULTS AND CONCLUSION: The comparison of neurological status dynamics during treatment of inpatients has shown that neurological symptoms reduce more effectively in patients treated with L - lysine aescinat (by 75% during the first 3-5 days) and in a greater number of the patients (77.5% vs 55% in the control group). The authors' experience has shown that venous micro- and macro-circulation disorders play an important role in the pathogenesis of lower lumbar disk hernia. Clinical manifestations of these disorders are segmental and conductive spinal motor disorders in myotomes and sensitivity. Quantitative determination of vibration sensitivity (tuning fork test) is pathognomonic for radiculomyeloischemia. Vein tonics and antiedemics, including L - lysine aescinat as one of the most effective drugs, exert a pathogenetic effect on spondylic and discogenic nervous system disturbances. PMID- 26356397 TI - [The neuroprotective therapy of outpatient treatment of chronic cerebral ischemia]. AB - AIM: To perform a differential analysis of the efficacy of combination therapy by the drugs with different modalities (mexidol, aescusan, halidorum) in outpatients with chronic cerebral ischemia (CCI), stages I- III. MATERIAL AND METHODS: A study included 50 patients with CCI of atherosclerotic, hypertensive and mixed genesis (stage I - 20 patients, stage II - 20, stage III - 10 patients). In addition to somatic therapy, patients received three courses of mexidol, halidorum and aescusan combination therapy during 6 weeks with a 3 month interval between the courses. The changes in subjective complaints and objective clinical manifestations were evaluated after each course. RESULTS AND CONCLUSION: The therapeutic efficacy after durable complex therapy by repeated courses of antioxidants is supported by the results of clinical and neurological examinations. Mexidol in the combination with aescusan and halidorum contributed to the improvement of cognitive, adaptive, motor functions of the patients with CCI, stages I and II. To increase treatment efficacy in patients with CCI, stage III, we recommend to use the drugs that improve cognitive functions of the patients. PMID- 26356398 TI - [Double blind placebo controlled randomized pilot clinical trial of baclofen (Baclosan(r)) for alcohol dependence]. AB - AIM: To study efficacy and safety of baclofen for treatment of alcohol dependence. MATERIAL AND METHODS: 32 patients with alcohol dependence had been randomized into one of two treatment groups (16 patients in each): patients of the 1st group were treated with baclofen (50 mg/day) for 3 months while patients of the 2nd one received identically looking placebo. All the study subjects were scheduled to come to the clinic on the weekly basis to control alcohol use and compliance with the study medications (by riboflavin marker in urine) and also - for psychiatric evaluations (severity of craving for alcohol, anxiety and depression). Alcohol use evaluated with the Time Line Follow Back technique and gamma-glutamiltranspeptidase activity in blood. To assess anxiety Spielberger state-trait inventory and Hamilton scale were used. Depression was assessed with Montgomery-Ashberg scale. To evaluate carving for alcohol used Obsessive Compulsive Drinking scale, Penn Alcohol Craving scale, and Visual Analog Scale of Craving. Overall treatment effect assessed with the Clinical Global Impression scale. The study design was double blind. RESULTS AND CONCLUSION: Baclofen did no differ significantly from placebo on either of primary or secondary outcome variables. However, primary outcome variables of retention in treatment and drinking were slightly better in the baclofen group compared to placebo, and those differences were close to the level of statistical significance. There were no differences between the groups in either rate of adverse events or liver enzymes activity which is an evidence of safety and good tolerability of baclofen in alcohol dependent patients. Further studies of baclofen for alcohol dependence in the larger sample size are needed. PMID- 26356399 TI - [The development of a pharmacologically active low-molecular mimetic of the nerve growth factor]. AB - Authors present an overview of theirs author's works on the design of low molecular mimetic of the nerve growth factor and studies of mechanisms of action and pharmacological properties of the compound. The original working hypothesis, underlying the design of the compound, posited that different neurotrophin hairpin loops could activate different signaling cascades by interaction with the receptor and so be responsible for different effects. The mimetic bis(N-succinyl L-glutamyl-L-lysine)hexametylendiamide (GK-2), that was designed on the basis of NGF loop 4 beta-turn sequence, activated TrkA and PI3K/Akt, but not MAPK/Erk. GK 2 showed neuroprotective activity in concentrations up to 10-9M against H(2)O(2) or glutamate or MPTP-induced neurotoxicity in RS12, NT22 cells and primary rat hippocampal neurons. At that, GK-2 has no differentiating activity. In in vivo experiments, GK-2 exhibited significant anti-ischemic, anti-parkinsonic effect, reversed impaired cognitive functions in models of Alzheimer's disease in doses 0.01 - 5 mg/kg intraperitoneally and 5-10 mg/kg orally, but does not induce side effects accompanying the full-length neurotrophin treatment, which are hyperalgesia and weight loss. It was shown that GK-2 was a low-toxicity compound (LD50=700 mg/kg, intraperitoneally, mice) and capable of crossing the blood-brain barrier. The agent GK-2 is promising for development as a neuroprotective agent and is currently in preclinical studies. PMID- 26356400 TI - [Effects of schizophrenic blood serum on astrocytes in human fetal brain organotypic culture: a morphometric study]. AB - AIM: To detect cytotoxic effects of blood serum (BS) from schizophrenia patients on astrocytes and neurons in the human fetal brain organotypic culture. MATERIAL AND METHODS: Authors studied the human fetal brain organotypic culture after the application of BS from 20 healthy donors and 33 untreated patients with attack like progressive schizophrenia (ICD-10: schizophrenia, paranoid type, F20.02; F20.22). The numerical density of degenerating cells was estimated by the optical dissector method in Nissl stained sections. A qualitative electron microscopic study of glial cells, neurons and neuropil as well as morphometric study of the ultrastructure of astrocytes were performed. RESULTS: Authors found no significant effect of BS from patients with schizophrenia on the numerical density of degenerating cells as compared to BS from healthy donors. The qualitative study detected ultrastructural alterations in astrocytes and microglial cells but not in neurons. The morphometric study of astrocytes demonstrated a decrease of the area of astrocytes, their nuclei (r<0.001) and cytoplasm (r<0.05), reduced number of mitochondria (r<0.05) and increase in the number and volume fraction of lypofuscin inclusions (r<0.01). CONCLUSION: The application of BS from untreated schizophrenia patients does not influence the cell survival in human fetal brain organotypic culture and the ultrastructure of neurons and neuropil but induces the hypotrophy of astrocytes and increase in the number of lypofuscin inclusions. The data suggest that astrocytes are specific target for the damage effect of BS from schizophrenia patients. PMID- 26356401 TI - [Release-active antibodies to S100 protein are able to improve the experimental allergic encephalomyelitis]. AB - AIM: To reveal the effects of release-active antibodies to S100 protein in an animal model of multiple sclerosis. MATERIAL AND METHODS: Sixty female Wistar rats, aged 12 weeks, were included in the study. The pathology was induced by subcutaneous injection of the spinal cord homogenate. Afterwards the rats received a water solution of release-active antibodies to S100 protein (2,5 ml/kg/day, tenoten) or distilled water intragastrically during 30 days. Intramuscular injections of glatiramer acetate (4 mg/kg/day, copaxone) were used as a positive control. RESULTS AND CONCLUSION: Release-active antibodies to S100 protein enhanced the latency period of the disease, reduced its peak intensity and compensated the loss of body weight of the animals. The experimental drug effect was similar to the results of copaxone injections. PMID- 26356402 TI - [Melatonin in the correction of sleep in post-stroke patients]. AB - AIM: To assess an effect of melatonin on quality of life and effectiveness of rehabilitation in patients with ischemic stroke (IS) suffered from insomnia due to sleep initiation disturbance. MATERIAL AND METHODS: Sixty post-stroke patients with insomnia were stratified into two groups matched for characteristics assessed in the study. Patients of the main group received melatonin during 21 days. In the first three days after admission and 21 days after the first examination, we administered the MMSE, the Rankin scale, FOSQ, NIHSS, EuroQol, the Epworth sleepiness scale (ESS) and used instrumental methods of examination (computed and magnetic-resonance tomography, electroencephalography, polysomnography). RESULTS: After 3 weeks, there was a reduction (p<0.05) in ESS scores in the main group compared to the control group (5.7 and 10 scores, respectively). Significant between-group differences were identified for polysomnographic parameters: latency to sleep was 17.8 min in the main group and 20.5 min in the control group (p<0.05), the number of microactivations was 15 and 18, respectively (p<0.05). There was a trend towards more rapid recovery in the main group (on average 8.4 days) compared to the control group (10.2 days), but the differences did not reach the level of statistical significance p<0.05. CONCLUSION: Melatonin reduced sleepiness (measured with the ESS), latency to sleep and number of wakings (microactivations) and was likely to promote the recovery in IS patients with insomnia due to sleep initiation disturbance. PMID- 26356403 TI - [Chronic cerebral ischemia associated with Raynaud's syndrome]. AB - Over the last years, a number of patients with chronic cerebral ischemia has been increased significantly. Compensatory possibilities of the brain and cerebral circulatory system are so great that even serious disturbances of blood circulation could not cause clinical signs of brain dysfunction for a long time. At the same time, long-term ischemia can lead to peripheral local disturbances of microcirculation that is appears to be a first signal of the problems with homeostasis. Therefore, Raynaud's syndrome may be one of the predictors of standard symptoms of chronic cerebral ischemia (CCI). This phenomenon is explicitly considered as a sign of blood circulation impairment while the pathogenetic mechanism of vascular arterial bed instability is completely ignored. Detailed study of clinical correlations of Raynaud's syndrome in CCI would help to develop a common pharmacotherapeutic approach to its treatment. PMID- 26356404 TI - [People's knowledge about dementia]. AB - Cognitive impairment is one of the most urgent problems due to the high prevalence and disability. Timely identification and early diagnosis of dementia are the most important for successful management of patients that may be possible only if patients refer for medical care. In this connection, people's knowledge about dementia is of great importance. To study people's knowledge about problems of dementia. The survey was carried out in September 2014 in 42 regions of the Russian Federation (130 survey sites) and comprised 1600 respondents. The survey has revealed that 48% of participants are afraid to have dementia, 47% are not aware of signs and symptoms of marked cognitive impairment and 54% have concerns about age-related memory impairment. A low percent of people who refer for medical care may be explained by the widespread opinion (37% of Russians) that dementia is not curable; 42% believe that there are no drugs for treatment of dementia. Only 5% of respondents would visit a doctor if their relative has dementia. The results of this survey highlighted the necessity of using special programs to improve people's knowledge about problems of dementia. PMID- 26356405 TI - Regioselective and Enantioselective Addition of Sulfur Nucleophiles to Acyclic alpha,beta,gamma,delta-Unsaturated Dienones Catalyzed by an Iron(III)-Salen Complex. AB - The first regioselective, enantioselective conjugate addition of thiols to acyclic alpha,beta,gamma,delta-unsaturated dienones at the delta carbon is described. The reaction, catalyzed by a chiral iron(III)-salen complex derived from cis-2,5-diaminobicyclo[2.2.2]octane as the scaffold, provides delta-thia alpha,beta-unsaturated ketones in high yield and enantioselectivity. The bicyclooctane scaffold of (2R,3R,5R,6R) configuration affords a delta-thia alpha,beta-unsaturated ketone of (R) configuration, indicating that the sulfur nucleophile is introduced at the si face of the gamma,delta-double bond. A model providing an explanation for this regio- and stereoselection is proposed. PMID- 26356406 TI - Unusual Presentation of Recurrent Pyogenic Bilateral Psoas Abscess Causing Bilateral Pulmonary Embolism by Iliac Vein Compression. AB - BACKGROUND: Psoas abscesses are a known cause of back pain, but they have not been reported as a cause of acute lower extremity thromboses and bilateral pulmonary emboli. We report a patient with bilateral psoas abscesses causing extensive pulmonary emboli through compression of the iliac vein. CASE REPORT: A 47-year-old man presented with bilateral leg swelling over 4 weeks. Physical examination revealed a thin male with bilateral leg swelling, extending to the thigh on his left side. He had hemoglobin of 10.5 g/dl, leukocytosis of 16 000/ml, and an elevated D-dimer. A computed tomography (CT) angiogram of his chest showed extensive bilateral pulmonary emboli and infarcts. He remained febrile with vague flank pain, prompting a CT of his abdomen and pelvis that showed large, multiloculated, septated, bilateral psoas abscesses with compression of the left femoral vein by the left psoas abscess and a thrombus distal to the occlusion. Two liters of pus was drained from the left psoas abscess by CT-guidance, and although the Gram staining showed Gram-positive cocci in clusters, cultures from the abscess and blood were negative. A repeat CT showed resolution of the abscesses, and the drain was removed. He was discharged to a nursing home to complete a course of intravenous antibiotics and anticoagulation. CONCLUSIONS: Although the infectious complications of psoas abscesses have been described in the literature, the mechanical complications of bilateral psoas abscesses are lacking. It is important to assess for complete resolution of psoas abscesses through follow-up imaging to prevent venous thromboembolic events. PMID- 26356407 TI - Effects of visibility and types of the ground surface on the muscle activities of the vastus medialis oblique and vastus lateralis. AB - [Purpose] The purpose of this study was to compare the effects of visibility and types of ground surface (stable and unstable) during the performance of squats on the muscle activities of the vastus medialis oblique (VMO) and vastus lateralis (VL). [Subjects and Methods] The subjects were 25 healthy adults in their 20s. They performed squats under four conditions: stable ground surface (SGS) with vision-allowed; unstable ground surface (UGS) with vision-allowed; SGS with vision-blocked; and UGS with vision-blocked. The different conditions were performed on different days. Surface electromyogram (EMG) values were recorded. [Results] The most significant difference in the activity of the VMO and VL was observed when the subjects performed squats on the UGS, with their vision blocked. [Conclusion] For the selective activation of the VMO, performing squats on an UGS was effective, and it was more effective when subjects' vision was blocked. PMID- 26356409 TI - Amyotrophic lateral sclerosis, channelopathies and peripheral neuropathies: current status and new perspectives. PMID- 26356408 TI - Effects of Mitochondrial Uncoupling Protein 2 Inhibition by Genipin in Human Cumulus Cells. AB - UCP2 plays a physiological role by regulating mitochondrial biogenesis, maintaining energy balance, ROS elimination, and regulating cellular autophagy in numerous tissues. But the exact roles of UCP2 in cumulus cells are still not clear. Genipin, a special UCP2 inhibitor, was added into the cultural medium to explore the roles of UCP2 in human cumulus cells. There were no significant differences in ATP and mitochondrial membrane potential levels in cumulus cells from UCP2 inhibiting groups as compared with the control. The levels of ROS and Mn-SOD were markedly elevated after UCP2 inhibited Genipin. However, the ratio of reduced GSH to GSSG significantly declined after treatment with Genipin. UCP2 inhibition by Genipin also resulted in obvious increase in the active caspase-3, which accompanied the decline of caspase-3 mRNA. The level of progesterone in culture medium declined obviously after Genipin treatment. But there was no significant difference in estradiol concentrations. This study indicated that UCP2 is expressed in human cumulus cells and plays important roles on mediate ROS production, apoptotic process, and steroidogenesis, suggesting UCP2 may be involved in regulation of follicle development and oocyte maturation and quality. PMID- 26356410 TI - Deciphering spreading mechanisms in amyotrophic lateral sclerosis: clinical evidence and potential molecular processes. AB - PURPOSE OF REVIEW: The aim of this review is to refer to recent arguments supporting the existence of specific propagation mechanisms associated with spreading of neuron injury in amyotrophic lateral sclerosis (ALS). RECENT FINDINGS: Misfolded ALS-linked protein accumulation can induce aggregation of their native equivalent isoforms through a mechanism analogous to the infectious prion proteins initiation and its propagation. SUMMARY: Although ALS is clinically heterogeneous, a shared characteristic is the focal onset and the progressive extension to all body regions. Being viewed until now as just summation of the increased number of affected neurons, dispersion is now rather considered as the result of a seeded self-propagating process. A sequential regional spreading pattern is supported by the distribution of TDP-43 aggregates in ALS autopsy cases. Electrophysiology and advanced neuroimaging methods also recently provided some evidence for propagation of lesions both in the brain and spinal cord, more longitudinal studies being still needed. Lesions are supposed to spread cell-to-cell regionally or through connected neuronal pathway. At the molecular level, the prion-like spreading is an emerging mechanism hypothesis, but other machineries such as those that are in charge of dealing with misfolded proteins and secretion of deleterious peptides may be involved in the propagation of neuron loss. Deciphering the mechanisms underlying spreading of ALS symptoms is of crucial importance to better understand this neurodegenerative disease, build new and appropriate animal models and to define novel therapeutic targets. PMID- 26356411 TI - Recent advances in familial amyloid polyneuropathy. AB - PURPOSE OF REVIEW: To highlight the advances in the knowledge of the clinical features, diagnostic techniques, clinimetrics, and therapeutics of transthyretin familial amyloid polyneuropathy. RECENT FINDINGS: Expanding knowledge of the molecular underpinnings and therapeutics of transthyretin familial amyloid polyneuropathy have provided impetus to molecular-specific phenotype characterization, natural history studies, and target-based therapeutic interventions. These interventions have underscored the need for early, accurate diagnostic instruments and sensitive diagnostic and therapeutic biomarkers. SUMMARY: Current and emerging target-based therapeutic interventions and novel diagnostic techniques may contribute to improved quality of life and survival in this disease. PMID- 26356412 TI - What can Duchenne Connect teach us about treating Duchenne muscular dystrophy? AB - PURPOSE OF REVIEW: This review aims to describe the benefits and limitations of using the Duchenne Connect patient registry to provide information particularly in regard to active treatment choices in Duchenne muscular dystrophy and their impact on disease progression. RECENT FINDINGS: Clinical trials and natural history studies are difficult for rare diseases like Duchenne muscular dystrophy. Using an online patient self-report survey model, Duchenne Connect provides relevant data that are difficult to gather in other ways. Validation of the overall dataset is supported by comparable mutational spectrum relative to other cohorts and demonstrated beneficial effect of corticosteroid use in prolonging ambulation. These types of analyses are provocative and allow multivariate analyses across the breadth of patient and physician medication and supplement practices. Because the data are self-reported and online, the barrier to participation is low and great potential exists for novel directions of further research in a highly participatory forum. SUMMARY: Patient registries for Duchenne and Becker muscular dystrophy (DBMD) are powerful tools for monitoring patient outcomes, comparing treatment options, and relating information between patients, researchers, and clinicians. Duchenne Connect is an online patient self report registry for individuals with DBMD that facilitates aggregation of treatment modalities, outcomes, and genotype data and has played a vital role in furthering DBMD research, particularly in the USA, in a highly participatory and low-cost manner. PMID- 26356415 TI - Here I Am, Despite Myself. PMID- 26356414 TI - Maternal-Fetal Hepatitis E Transmission: Is It Underestimated? AB - Hepatitis E virus (HEV) is an enterically transmitted virus; and several modes of transmission have been proposed, including blood transfusion, person to person transmission, and transplacental transmission. HEV during pregnancy is associated with an unfavorable prognosis for mothers and in severe cases can cause acute fulminate hepatitis and death. Transplacental transmission of HEV usually results in unfavorable outcomes of pregnancy, mainly fetal loss, preterm labor, and hepatic dysfunction in neonates. In this review, we will summarize the effects of HEV on maternal-fetal health in various clinical situations. PMID- 26356416 TI - Sulfur Reduction in Acid Rock Drainage Environments. AB - Microbiological suitability of acidophilic sulfur reduction for metal recovery was explored by enriching sulfur reducers from acidic sediments at low pH (from 2 to 5) with hydrogen, glycerol, methanol and acetate as electron donors at 30 degrees C. The highest levels of sulfide in the enrichments were detected at pH 3 with hydrogen and pH 4 with acetate. Cloning and sequencing of the 16S rRNA gene showed dominance of the deltaproteobacterial sulfur-reducing genus Desulfurella in all the enrichments and subsequently an acidophilic strain (TR1) was isolated. Strain TR1 grew at a broad range of pH (3-7) and temperature (20-50 degrees C) and showed good metal tolerance (Pb(2+), Zn(2+), Cu(2+), Ni(2+)), especially for Ni(2+) and Pb(2+), with maximal tolerated concentrations of 0.09 and 0.03 mM, respectively. Different sources of sulfur were tested in the enrichments, from which biosulfur showed fastest growth (doubling time of 1.9 days), followed by colloidal, chemical and sublimated sulfur (doubling times of 2.2, 2.5, and 3.6 days, respectively). Strain TR1's physiological traits make it a good candidate to cope with low pH and high metal concentration in biotechnological processes for treatment of metal-laden acidic streams at low and moderately high temperature. PMID- 26356417 TI - The Human Homolog of Drosophila Headcase Acts as a Tumor Suppressor through Its Blocking Effect on the Cell Cycle in Hepatocellular Carcinoma. AB - The molecular pathogenesis of hepatocellular carcinoma (HCC) is heterogeneous and extremely complex. Thus, for individual molecular targeted therapy, novel molecular markers are needed. The abnormal expression of the human homolog of Drosophila headcase (HECA homo) has been found in pancreatic, colorectal, and oral squamous cell carcinoma. Studies of oral squamous cell carcinoma have also demonstrated that the HECA homo protein can be negatively controlled by the Wnt pathway and transcription factor 4 (TCF4) and can slow cell division by interacting with cyclins and CDKs. However, the role of HECA in HCC has not been reported elsewhere. Here, immunohistochemical analysis revealed that the downregulation of HECA homo protein occurred in 71.0% (66/93) of HCC cases and was positively correlated with a poorly differentiated grade, high serum AFP level, liver cirrhosis and large tumor size. The expression of HECA homo was detected in five live cell lines. In vitro, the overexpression of HECA homo in HepG2, Huh-7 and MHCC-97H cells could inhibit cell proliferation and colony formation and induce G1 phase arrest. In contrast, the downregulation of HECA homo could promote cell proliferation, colony formation and the cell cycle process. However, neither the overexpression nor downregulation of HECA homo in the three cell lines could affect cell migration or invasion. Collectively, HECA homo is regularly expressed in normal live cells, and the HECA homo protein level is heterogeneously altered in HCC, but the downregulation of HECA homo is more common and positively correlated with several malignant phenotypes. The HECA homo protein can slow cell proliferation to some extent primarily through its blocking effect on the cell cycle. Hence, the HECA homo protein may act as a tumor suppressor in HCC and might be a potential molecular marker for diagnostic classification and targeted therapy in HCC. PMID- 26356418 TI - Nuclear envelope-associated endosomes deliver surface proteins to the nucleus. AB - Endocytosis directs molecular cargo along three main routes: recycling to the cell surface, transport to the Golgi apparatus or degradation in endolysosomes. Pseudomonas exotoxin A (PE) is a bacterial protein that typically traffics to the Golgi and then the endoplasmic reticulum before translocating to the cytosol. Here we show that a substantial fraction of internalized PE is also located in nuclear envelope-associated endosomes (NAE), which display limited mobility, exhibit a propensity to undergo fusion and readily discharge their contents into the nuclear envelope. Electron microscopy and protein trapping in the nucleus indicate that NAE mediate PE transfer into the nucleoplasm. RNAi screening further revealed that NAE-mediated transfer depends on the nuclear envelope proteins SUN1 and SUN2, as well as the Sec61 translocon complex. These data reveal a novel endosomal route from the cell surface to the nucleoplasm that facilitates the accumulation of extracellular and cell surface proteins in the nucleus. PMID- 26356421 TI - Comment on "Necrotizing Urethritis due to Aerococcus urinae". PMID- 26356420 TI - Perfluoroalkyl Acid Concentrations in Blood Samples Subjected to Transportation and Processing Delay. AB - BACKGROUND: In studies of perfluoroalkyl acids, the validity and comparability of measured concentrations may be affected by differences in the handling of biospecimens. We aimed to investigate whether measured plasma levels of perfluoroalkyl acids differed between blood samples subjected to delay and transportation prior to processing and samples with immediate processing and freezing. METHODS: Pregnant women recruited at Aarhus University Hospital, Denmark, (n = 88) provided paired blood samples. For each pair of samples, one was immediately processed and plasma was frozen, and the other was delayed and transported as whole blood before processing and freezing of plasma (similar to the Danish National Birth Cohort). We measured 12 perfluoroalkyl acids and present results for compounds with more than 50% of samples above the lower limit of quantification. RESULTS: For samples taken in the winter, relative differences between the paired samples ranged between -77 and +38% for individual perfluoroalkyl acids. In most cases concentrations were lower in the delayed and transported samples, e.g. the relative difference was -29% (95% confidence interval -30; -27) for perfluorooctane sulfonate. For perfluorooctanoate there was no difference between the two setups [corresponding estimate 1% (0, 3)]. Differences were negligible in the summer for all compounds. CONCLUSIONS: Transport of blood samples and processing delay, similar to conditions applied in some large, population-based studies, may affect measured perfluoroalkyl acid concentrations, mainly when outdoor temperatures are low. Attention to processing conditions is needed in studies of perfluoroalkyl acid exposure in humans. PMID- 26356419 TI - Relative Importance of Aortic Stiffness and Volume as Predictors of Treatment Induced Improvement in Left Ventricular Mass Index in Dialysis. AB - This study aimed to explore the relative contribution of aortic stiffness and volume in treatment-induced change of left ventricular mass in dialysis. Hypertension in Hemodialysis Patients Treated with Atenolol or Lisinopril trial compared the effect of lisinopril versus atenolol in reducing left ventricular mass index; 179 patients with echo measurements of aortic pulse wave velocity and left ventricular mass at baseline were included. In unadjusted analysis, overall reductions of 26.24 g/m2 (95% CI: -49.20, -3.29) and 35.67 g/m2 (95% CI: -63.70, 7.64) in left ventricular mass index were noted from baseline to 6 and 12 months respectively. Volume control emerged as an important determinant of regression of left ventricular mass index due to the following reasons: (i) additional control for change in ambulatory systolic blood pressure mitigated the reduction in left ventricular mass index in the statistical model above [6-month visit: -18.6 g/m2 (95% CI: -43.7, 6.5); 12-month visit: -22.1 g/m2 (95% CI: -52.2, 8.0)] (ii) regression of left ventricular hypertrophy was primarily due to reduction in left ventricular chamber and not wall thickness and (iii) adjustment for inferior vena cava diameter (as a proxy for volume) removed the effect of time on left ventricular mass index reduction [6-month visit: -6.6 g/m2 (95% CI: (-41.6, 28.4); 12-month visit: 0.6 g/m2 (95% CI: -39.5, 40.7)]. In contrast, aortic pulse wave velocity was neither a determinant of baseline left ventricular mass index nor predictor of its reduction. Among dialysis patients, ambulatory systolic pressure, a proxy for volume expansion, but not aortic stiffness is more important predictor of reduction in left ventricular mass index. Improving blood pressure control via adequate volume management appears as an effective strategy to improve left ventricular hypertrophy in dialysis. PMID- 26356422 TI - Synthetic deoxynojirimycin derivatives bearing a thiolated, fluorinated or unsaturated N-alkyl chain: identification of potent alpha-glucosidase and trehalase inhibitors as well as F508del-CFTR correctors. AB - The synthesis of eleven 1-deoxynojirimycin (DNJ) derivatives presenting either a monofluoro, difluoro, thiolated or unsaturated N-alkyl chain of various length is described. Exploiting the unsaturated moiety on the nitrogen, fluorine has been introduced through a HF/SbF5 superacid catalysed hydrofluorination and thiol-ene click chemistry allowed introduction of sulfur. The synthetic derivatives have been tested for their ability to inhibit glycosidases and correct F508del-CFTR. Two of the unsaturated iminosugars exhibited potency similar to Miglustat as F508del-CFTR correctors. The thioalkyl iminosugars as well as the corresponding alkyl iminosugars demonstrated low micromolar alpha-glucosidases and trehalases inhibition. Introduction of fluorine abolished F508del-CFTR correction and trehalase inhibition. PMID- 26356423 TI - Health policy - more ideology than rationality? PMID- 26356424 TI - An indispensable tool. PMID- 26356425 TI - [Re: Where the sun never shines]. PMID- 26356426 TI - [The editor replies]. PMID- 26356427 TI - [Re: How do we compare quality of health care?]. PMID- 26356428 TI - [M. Asplin & E. Fagermoen reply]. PMID- 26356429 TI - [Re: How do we compare quality of health care?]. PMID- 26356430 TI - [Re: How do we compare quality of health care?]. PMID- 26356431 TI - [Re: How do we compare quality of health care?]. PMID- 26356432 TI - [Re: E-cigarettes--harmful or beneficial?]. PMID- 26356433 TI - [T. Sanner & T.K. Grimsrud reply]. PMID- 26356436 TI - [Re: E-cigarettes--harmful or beneficial?]. PMID- 26356437 TI - [Re: Our international colleagues]. PMID- 26356438 TI - [S. Shaygani replies]. PMID- 26356439 TI - [Re: Typical growth pattern in malignant pleural mesothelioma]. PMID- 26356444 TI - [Re: Markov modeling]. PMID- 26356445 TI - [E. Nord replies]. PMID- 26356448 TI - [Varying access to pediatric radiological expertise]. PMID- 26356449 TI - Giardia outbreak in Bergen 2004 - what was the source of infection? PMID- 26356450 TI - Criteria-based diagnostics generate excessive and incorrect diagnoses. PMID- 26356451 TI - [The practice consultant scheme at a crossroads]. PMID- 26356454 TI - Treatment for psychogenic non-epileptic seizures. AB - The main differential diagnosis of epilepsy among young adults is psychogenic non epileptic seizures. Such seizures may manifest themselves in very different ways and usually have complex root causes. Optimal treatment of persons experiencing seizures of this type requires close cooperation between the neurologist and the psychiatrist. PMID- 26356455 TI - [Black skin blisters and Enterobacter in the blood]. PMID- 26356456 TI - [ An infant with acute flaccid pareses]. PMID- 26356457 TI - [A woman in her 60s with itching arms]. PMID- 26356458 TI - Why the p-value is significant. PMID- 26356459 TI - [What can we say about causality?]. PMID- 26356460 TI - [A clinician and a bayesian]. PMID- 26356461 TI - [Medicine and market]. PMID- 26356462 TI - Overweight or obese - you are not your condition. PMID- 26356463 TI - E. Hem responds. PMID- 26356467 TI - [Physicians' alcohol habits are changing]. PMID- 26356474 TI - Ultrathin Wrinkled N-Doped Carbon Nanotubes for Noble-Metal Loading and Oxygen Reduction Reaction. AB - We describe the fabrication of ultrathin wrinkled N-doped carbon nanotubes by an in situ solid-state method. The positions of Co catalyst were first labeled by good-dispersion and highly loaded Au and Pt, indicating the most of Co are unsealed. The resultant unique nanoarchitecture, which exhibits the features of carbon nanotube and graphene with a combined effect of 1D and 2D carbon-based nanostructures, exhibited a superior ORR activity to carbon nanotubes and graphene. Moreover, the novel catalysts showed a better durability and higher tolerance to methanol crossover and poisoning effects than those of Pt/C. PMID- 26356476 TI - Dull Brains, Mountaineers, and Mosso: Hypoxic Words from on High. AB - Dull and hypoxic brains have been a frequent subject in the medical and mountaineering literature. Deterioration of cognitive and other neurological function occurs at high altitude, with or without high altitude cerebral edema. This historical essay explores a 2014 first-ever English translation of cerebral blood flow studies by nineteenth century physiologist Angelo Mosso. Some of the medical history and physiology of brain function is discussed, but much of the style focuses on quotations from the writings of mountaineers and mountaineering physicians to provide color commentary about dull brains at high altitude. PMID- 26356475 TI - Network Modeling Reveals Cross Talk of MAP Kinases during Adaptation to Caspofungin Stress in Aspergillus fumigatus. AB - Mitogen activated protein kinases (MAPKs) are highly conserved in eukaryotic organisms. In pathogenic fungi, their activities were assigned to different physiological functions including drug adaptation and resistance. Aspergillus fumigatus is a human pathogenic fungus, which causes life-threatening invasive infections. Therapeutic options against invasive mycoses are still limited. One of the clinically used drugs is caspofungin, which specifically targets the fungal cell wall biosynthesis. A systems biology approach, based on comprehensive transcriptome data sets and mathematical modeling, was employed to infer a regulatory network and identify key interactions during adaptation to caspofungin stress in A. fumigatus. Mathematical modeling and experimental validations confirmed an intimate cross talk occurring between the cell wall-integrity and the high osmolarity-glycerol signaling pathways. Specifically, increased concentrations of caspofungin promoted activation of these signalings. Moreover, caspofungin affected the intracellular transport, which caused an additional osmotic stress that is independent of glucan inhibition. High concentrations of caspofungin reduced this osmotic stress, and thus decreased its toxic activity. Our results demonstrated that MAPK signaling pathways play a key role during caspofungin adaptation and are contributing to the paradoxical effect exerted by this drug. PMID- 26356477 TI - What Are Physicians' Reasons for Not Referring People with Life-Limiting Illnesses to Specialist Palliative Care Services? A Nationwide Survey. AB - BACKGROUND: Many people who might benefit from specialist palliative care services are not using them. AIM: We examined the use of these services and the reasons for not using them in a population in potential need of palliative care. METHODS: We conducted a population-based survey regarding end-of-life care among physicians certifying a large representative sample (n = 6188) of deaths in Flanders, Belgium. RESULTS: Palliative care services were not used in 79% of cases of people with organ failure, 64% of dementia and 44% of cancer. The most frequently indicated reasons were that 1) existing care already sufficiently addressed palliative and supportive needs (56%), 2) palliative care was not deemed meaningful (26%) and 3) there was insufficient time to initiate palliative care (24%). The reasons differed according to patient characteristics: in people with dementia the consideration of palliative care as not meaningful was more likely to be a reason for not using it; in older people their care needs already being sufficiently addressed was more likely to be a reason. For those patients who were referred the timing of referral varied from a median of six days before death (organ failure) to 16 days (cancer). CONCLUSIONS: Specialist palliative care is not initiated in almost half of the people for whom it could be beneficial, most frequently because physicians deem regular caregivers to be sufficiently skilled in addressing palliative care needs. This would imply that the safeguarding of palliative care skills in this regular 'general' care is an essential health policy priority. PMID- 26356478 TI - Does Changing Vertical Disparity Induce Horizontal Head Movement? AB - Theoretically, one can estimate the direction of an object that is relative to the head using vertical disparity if the distance from the head to the object is known. However, several reports describe vertical disparity as having little or no effect on the perception of visual direction. It has been suggested, however, that the visual processes involved in action are different from those involved in perception, and the effect of visual disparity on action has not been investigated in previous studies. This study investigated the influence of vertical disparity on the stability of head direction as a motor response to visual information. We presented a stimulus consisting of horizontal lines with vertical size-disparity oscillation, and examined whether the stimulus affected the subject's head movement. The results showed that the head movement in the condition of vertical size-disparity oscillation was not significantly different from that in the condition of no disparity oscillation. Our results suggest that, despite theoretical validity, vertical disparity is not used for controlling head movement. PMID- 26356479 TI - Discrimination of grasshopper (Orthoptera: Acrididae) diet and niche overlap using next-generation sequencing of gut contents. AB - Species of grasshopper have been divided into three diet classifications based on mandible morphology: forbivorous (specialist on forbs), graminivorous (specialist on grasses), and mixed feeding (broad-scale generalists). For example, Melanoplus bivittatus and Dissosteira carolina are presumed to be broad-scale generalists, Chortophaga viridifasciata is a specialist on grasses, and Melanoplus femurrubrum is a specialist on forbs. These classifications, however, have not been verified in the wild. Multiple specimens of these four species were collected, and diet analysis was performed using DNA metabarcoding of the gut contents. The rbcLa gene region was amplified and sequenced using Illumina MiSeq sequencing. Levins' measure and the Shannon-Wiener measure of niche breadth were calculated using family-level identifications and Morisita's measure of niche overlap was calculated using operational taxonomic units (OTUs). Gut contents confirm both D. carolina and M. bivittatus as generalists and C. viridifasciata as a specialist on grasses. For M. femurrubrum, a high niche breadth was observed and species of grasses were identified in the gut as well as forbs. Niche overlap values did not follow predicted patterns, however, the low values suggest low competition between these species. PMID- 26356481 TI - Effects of Continuous and Interval Training on Running Economy, Maximal Aerobic Speed and Gait Kinematics in Recreational Runners. AB - The purpose of this study was to evaluate the effects on running economy (RE), V[Combining Dot Above]O2max, maximal aerobic speed (MAS), and gait kinematics (step length [SL] and frequency, flight and contact time [CT]) in recreational athletes, with 2 different training methods, Interval and Continuous (CON). Eleven participants were randomly distributed in an interval training group (INT; n = 6) or CON training group (CON; n = 5). Interval training and CON performed 2 different training programs (95-110% and 70-75% of MAS, respectively), which consisted of 3 sessions per week during 6 weeks with the same external workload (%MAS * duration). An incremental test to exhaustion was performed to obtain V[Combining Dot Above]O2max, MAS, RE, and gait variables (high speed camera) before and after the training intervention. There was a significant improvement (p <= 0.05) in RE at 60 and 90% of MAS by the CON group; without changes in gait. The INT group significantly increased MAS and higher stride length at 80, 90, and 100% of MAS and lower CT at 100% of MAS. As expected, training adaptations are highly specific to the overload applied with CON producing improvements in RE at lower percentage of MAS whereas INT produces improvements in MAS. The significantly increased stride length and decreased CT for the INT group are an important outcome of favorable changes in running gait. PMID- 26356480 TI - Quantification of histone modifications by parallel-reaction monitoring: a method validation. AB - Abnormal epigenetic reprogramming is one of the major causes leading to irregular gene expression and regulatory pathway perturbations, in the cells, resulting in unhealthy cell development or diseases. Accurate measurements of these changes of epigenetic modifications, especially the complex histone modifications, are very important, and the methods for these measurements are not trivial. By following our previous introduction of PRM to targeting histone modifications (Tang, H.; Fang, H.; Yin, E.; Brasier, A. R.; Sowers, L. C.; Zhang, K. Multiplexed parallel reaction monitoring targeting histone modifications on the QExactive mass spectrometer. Anal. Chem. 2014, 86 (11), 5526-34), herein we validated this method by varying the protein/trypsin ratios via serial dilutions. Our data demonstrated that PRM with SILAC histones as the internal standards allowed reproducible measurements of histone H3/H4 acetylation and methylation in the samples whose histone contents differ at least one-order of magnitude. The method was further validated by histones isolated from histone H3 K36 trimethyltransferase SETD2 knockout mouse embryonic fibroblasts (MEF) cells. Furthermore, histone acetylation and methylation in human neural stem cells (hNSC) treated with ascorbic acid phosphate (AAP) were measured by this method, revealing that H3 K36 trimethylation was significantly down-regulated by 6 days of treatment with vitamin C. PMID- 26356482 TI - Efficacy of a Ventilatory Training Mask to Improve Anaerobic and Aerobic Capacity in Reserve Officers' Training Corps Cadets. AB - The purpose of this study was to examine the efficacy of a ventilatory training mask to improve anaerobic and aerobic fitness in reserve officers' training corps (ROTC) cadets. Seventeen ROTC cadets from a Midwest university completed pre- and postassessments consisting of anthropometry, a 30-second Wingate Anaerobic Test (WAnT), and a maximal aerobic capacity test (V[Combining Dot Above]O2max). A 6 week intervention training period was used during which time participants completed their mandatory physical training (PT) sessions. Participants were randomly assigned to either the experimental group (MASK; n = 9) or the control group (CON; n = 8). The ventilatory training masks were adjusted to simulate an altitude of 2,750 m. There was no significant effect (p <= 0.05) between groups on fatigue index, anaerobic capacity, peak power, V[Combining Dot Above]O2max, or time to exhaustion. These results suggest that the use of the ventilatory training mask during mandatory PT did not elicit superior aerobic or anaerobic adaptations in ROTC cadets. Therefore, it is recommended that more established simulated altitude training methods be used when incorporating intermittent hypoxic training. PMID- 26356483 TI - Pyruvate Dehydrogenase Activity Is Decreased in the Peripheral Blood Mononuclear Cells of Patients with Sepsis. A Prospective Observational Trial. AB - RATIONALE: Rodent studies have shown that pyruvate dehydrogenase (PDH) levels are low in sepsis. This may cause cells to shift to anaerobic metabolism, resulting in increased lactate production. Alterations in PDH during sepsis have never been studied in humans. OBJECTIVES: The objective of this pilot study was to measure PDH activity and quantity in patients with severe sepsis. METHODS: We conducted a pilot case-control study at a single urban tertiary care center. We compared PDH activity and quantity between patients with severe sepsis admitted to the intensive care unit and healthy control subjects. PDH activity and quantity were measured in isolated peripheral blood mononuclear cells. We measured PDH activity and quantity in control subjects at baseline and in patients with sepsis at 0 (baseline), 24, 48, and 72 hours. MEASUREMENTS AND MAIN RESULTS: We enrolled 56 patients with sepsis and 20 control subjects with at least one blood sample being drawn from each patient. PDH activity and quantity in the sepsis group were significantly lower than the control group (P < 0.001). In multivariable linear regression adjusting for age, race, sex, and assay plate, the difference remained significant. Patients with sepsis who died had significantly lower PDH activity compared with those who survived (P = 0.03). CONCLUSIONS: PDH activity and quantity is decreased in peripheral blood mononuclear cells of humans with severe sepsis when compared with healthy control subjects, and may be associated with mortality. Whether decreased PDH activity plays a role in lactate metabolism or whether pharmacologic modification of PDH activity may improve outcomes remains unknown. PMID- 26356484 TI - Rational Control of Polyketide Extender Units by Structure-Based Engineering of a Crotonyl-CoA Carboxylase/Reductase in Antimycin Biosynthesis. AB - Bioengineering of natural product biosynthesis is a powerful approach to expand the structural diversity of bioactive molecules. However, in polyketide biosynthesis, the modification of polyketide extender units, which form the carbon skeletons, has remained challenging. Herein, we report the rational control of polyketide extender units by the structure-based engineering of a crotonyl-CoA carboxylase/reductase (CCR), in the biosynthesis of antimycin. Site directed mutagenesis of the CCR enzyme AntE, guided by the crystal structure solved at 1.5 A resolution, expanded its substrate scope to afford indolylmethylmalonyl-CoA by the V350G mutation. The mutant A182L selectively catalyzed carboxylation over the regular reduction. Furthermore, the combinatorial biosynthesis of heterocycle- and substituted arene-bearing antimycins was achieved by an engineered Streptomyces strain bearing AntE(V350G). These findings deepen our understanding of the molecular mechanisms of the CCRs, which will serve as versatile biocatalysts for the manipulation of building blocks, and set the stage for the rational design of polyketide biosynthesis. PMID- 26356485 TI - Evaluating a common semi-mechanistic mathematical model of gene-regulatory networks. AB - Modeling and simulation of gene-regulatory networks (GRNs) has become an important aspect of modern systems biology investigations into mechanisms underlying gene regulation. A key challenge in this area is the automated inference (reverse-engineering) of dynamic, mechanistic GRN models from gene expression time-course data. Common mathematical formalisms for representing such models capture two aspects simultaneously within a single parameter: (1) Whether or not a gene is regulated, and if so, the type of regulator (activator or repressor), and (2) the strength of influence of the regulator (if any) on the target or effector gene. To accommodate both roles, "generous" boundaries or limits for possible values of this parameter are commonly allowed in the reverse engineering process. This approach has several important drawbacks. First, in the absence of good guidelines, there is no consensus on what limits are reasonable. Second, because the limits may vary greatly among different reverse-engineering experiments, the concrete values obtained for the models may differ considerably, and thus it is difficult to compare models. Third, if high values are chosen as limits, the search space of the model inference process becomes very large, adding unnecessary computational load to the already complex reverse-engineering process. In this study, we demonstrate that restricting the limits to the [-1, +1] interval is sufficient to represent the essential features of GRN systems and offers a reduction of the search space without loss of quality in the resulting models. To show this, we have carried out reverse-engineering studies on data generated from artificial and experimentally determined from real GRN systems. PMID- 26356486 TI - Hypoxia Potentiates LPS-Mediated Cytotoxicity of BV2 Microglial Cells In Vitro by Synergistic Effects on Glial Cytokine and Nitric Oxide System. AB - BACKGROUND: Microglial activation due to a variety of stimuli induces secretion of neurotoxic substances including inflammatory cytokines and nitric oxide (NO). Clinical studies indicate a cross-link between inflammatory and hypoxia-regulated pathways suggesting that bacterial infections markedly sensitize the immature brain to hypoxic injury. METHODS: The impact of inflammation and hypoxia on interleukin (IL)-1beta, IL-6, tumor necrosis factor alpha (TNF-alpha), and NO secretion and microglia-induced cytotoxicity was investigated exposing BV2 cells to lipopolysaccharides (LPS) and hypoxia (1% O2). Cytotoxicity, NO, and cytokine release was quantified by MTS and Griess assays and by enzyme-linked immunosorbent assays, respectively. RESULTS: LPS exposure of BV2 cells induced a significant, persistent production of NO, IL-1beta, IL-6, and TNF-alpha. Even after LPS removal, ongoing NO and cytokine secretion was observed. Hypoxia mediated exclusively a significant, short-term IL-1beta increase, but enhanced LPS-induced cytokine and NO secretion significantly. In addition, LPS-induced supernatants exhibited a stronger cytotoxic effect in glial and neuronal cells than LPS exposition (p < 0.001). Hypoxia potentiated LPS-induced cytotoxicity. CONCLUSION: Present data prove that LPS-induced soluble factors rather than LPS exposure mediate microglial toxicity under conditions of hypoxia in vitro. Apart from potential protective effects of the hypoxia-inducible transcription factor (HIF)-1alpha system, activation of proinflammatory pathways may markedly sensitize microglial cells to promote hypoxia-induced injuries of the developing brain. PMID- 26356487 TI - Inflammatory Characteristics of Monocytes from Pediatric Patients with Tuberous Sclerosis. AB - OBJECTIVE: Therapeutic options for the tuberous sclerosis complex (TSC) syndrome showed varying outcomes. Malfunctional tsc1/tsc2 genes leave mTOR uninhibited, a positive downstream modulator of the innate proinflammatory immune system, which has not yet been described in pediatric patients with TSC. METHODS: Using polymerase chain reaction (PCR) gene expression levels of monocytes after cultivation with lipopolysaccharide (LPS) or with LPS + mTOR inhibitor rapamycin, patients with TSC (n = 16) were compared with healthy subjects (n = 20). RESULTS: Compared with monocytes from healthy controls, LPS showed a more prominent gene expression pattern in patients with TSC (CCL24, CXCL10, IL-6, IL-10, and IL-1B). Proinflammatory reactions against LPS were modulated by rapamycin. With LPS + rapamycin monocytes from patients with TSC showed gene expression patterns different from healthy subjects. Furthermore, developmental differences were discernible in patients with TSC, compared with gene expression levels for patients 0 to 5 years to those 6 to 11 years of age, the latter with marked expression of IL-6 IL-1A, IL-1B, RIPK2, but also IL-10. CONCLUSION: The effects of LPS, even more of LPS with rapamycin on monocytes from patients with TSC suggested that inflammatory processes are distinct from those in healthy subjects. Furthermore, reaction to rapamycin indicates age-related gene expression levels. Our findings offer a model to decipher the unknown and varying gene expression pattern induced by rapamycin. PMID- 26356488 TI - High pressure jet injection of viscous solutions for endoscopic submucosal dissection (ESD): first clinical experience. AB - BACKGROUND: Long lasting elevation is a key factor during endoscopic submucosal dissection (ESD) and can be obtained by water jet injection of saline solution or by viscous macromolecular solutions. In a previous animal study, we assessed the Nestis Enki II system to combine jet injection and viscous solutions. In the present work, we used this combination in humans in different sites of the digestive tract. METHODS: We retrospectively report all of the consecutive ESD procedures performed with jet injection of viscous solutions in four centers. Information was collected about the lesion, the procedure, the histological result, and the outcomes for the patient. RESULTS: In total, 45 resections were completed by six operators: five experts and one beginner with only one previous experience in human ESD. Lesions were located in the esophagus (10), the stomach (11), the duodenum (1), the colon (1) and the rectum (22). Average maximal lesion diameter was 4.8 cm (SD 2.4, range 2 - 11 cm), average lesion surface area was 19.8 cm(2) (SD 17.7, range 2.2 - 72 cm(2)), and average duration of procedure was 79.9 min (SD 50.3 min, range 19 - 225 min). ESD could be conducted while the endoscope was retroflexed at its maximum in 26 cases. Four adverse events were observed: two diminutive perforations and two delayed bleeding occurrences treated conservatively. The R0 resection rate was 91.1 %. The catheter was obstructed in six occurrences of bleeding. CONCLUSION: Endoscopic submucosal dissection using high pressure injection of viscous macromolecular solutions is safe and effective in different parts of the digestive tract. It does not impede working with the endoscope in the maximal retroflexed position. PMID- 26356489 TI - Ultrasonographic and pathologic study of schwannoma in a Goldfish (Carassius auratus). AB - An adult Goldfish (Carassius auratus) developed an exophitic, multinodular, mass in the dorsal region involving the fin. The clinical and pathologic approach included ultrasonography, cytology, histopathology, immunohistochemistry, and ultrastructural evaluation. B-mode and color Doppler ultrasonographic findings showed an oval, well-defined mass with slightly inhomogeneous parenchymatous echotexture associated with an intense intralesional vascularization. Cytology and histology revealed neoplastic pleomorphic spindle cells arranged in a storiform pattern or in palisades typical of Antoni A pattern schwannoma. Moderate anisocytosis and anisokaryosis and occasional binucleation were also present. The neoplastic tissue deeply infiltrated the skeletal muscle of the dorsal region. Immunohistochemistry showed a diffuse cytoplasmic immunoreactivity of neoplastic cells to S100 protein and proliferating cell nuclear antigen (PCNA); glial fibrillary acidic protein was negative. The PCNA proliferation rate was 23.5% (calculated as the mean of 10 fields). Ultrastructurally, neoplastic cells were juxtaposed with parallel nuclei forming the typical palisade pattern and sharing cytoplasmic and nuclear features with human schwannoma. This is the first cytologic description supplied with echographic investigation of a malignant schwannoma in a fish species. PMID- 26356490 TI - Dynamic Properties of Glass-Formers Governed by the Frequency Dispersion of the Structural alpha-Relaxation: Examples from Prilocaine. AB - General and fundamental properties of glass-formers of various chemical bonding and physical structures have been found in the recent past. These important findings should be key to gain basic understanding of the dynamics at all time scales leading to glass transition. However, the entirety of these general properties has not been found in a single glass-former. For others to appreciate the importance of these properties, they need to collect the supporting experimental data from different glass-formers scattered over many publications. This hurdle may account for the current lack of universal recognition of the importance of these general properties by the research community. In this paper we present experimental studies of the dynamic processes over a broad range of time scales of a single glass-former, prilocaine. Practically the entire collection of fundamental properties has been found in this system. The advance should heighten the awareness of the importance of these properties in anyone's effort to solve the glass transition problem. PMID- 26356491 TI - Modified contrast microinjection technique to facilitate chronic total occlusion recanalization. AB - OBJECTIVES: To assess the efficacy and safety of the modified contrast microinjection technique to facilitate chronic total occlusion recanalization. BACKGROUND: The success rate of chronic total occlusion percutaneous coronary intervention (CTO-PCI) does not exceed 90% even in the most experienced centres. We have previously demonstrated that a large volume of contrast injected into the subintimal space can facilitate recanalization but is limited by a risk of serious complication. The aim of this study was to assess the application, efficacy and safety of a modified contrast microinjection technique that utilizes the injection of a much smaller volume of contrast in CTO-PCI. METHODS: A retrospective analysis of patients in whom the modified microinjection technique was utilised in patients undergoing CTO-PCI at five tertiary centres was conducted. RESULTS: Of 1,192 patients who underwent CTO-PCI, the microinjection technique was used in 59 patients (4.7%). The majority of CTOs treated were in the right coronary artery (79.7%), were of high complexity and 35.6% of lesions had a least one previously failed PCI attempt. The modified microinjection technique was used for more than one indication in 7 (11.9%) of patients. The success rate was 81.4%. There were no procedural complications related to the use of the reported modified microinjection. CONCLUSION: Initial experience with the modified microinjection demonstrates that it can be performed safely, is reproducible, and is broadly applicable. Whilst not required for all CTO procedures it can be a helpful adjunctive tool to increase the likelihood of success especially in complex, or refractory cases, without compromising the safety of the procedure. (c) 2015 Wiley Periodicals, Inc. PMID- 26356492 TI - The Importance of Corneal Endothelial Cell Survival After Endothelial Keratoplasty. PMID- 26356493 TI - Inferior vena cava reconstruction for leiomyosarcoma of Zone I-III requiring complete hepatectomy and bilateral nephrectomy with autotransplantation. AB - The inferior vena cava (IVC) is the most common site of leiomyosarcomas arising from a vascular origin. Leiomyosarcomas of the IVC are categorized by anatomical location. Zone I refers to the infrarenal portion of the IVC, Zone II from the hepatic veins to the renal veins, and Zone III from the right atrium to the hepatic veins. This is a rare presentation of a Zone I-III leiomyosarcoma. Fifty two-years-old female with a medical history significant only for HTN was admitted to the hospital with bilateral lower extremity edema and dyspnea. Two-dimensional echo demonstrated a right atrial thrombus, extending into the IVC. On subsequent CT and MRI, a 15 cm mass was noted that began in the right atrium and extended into the IVC, with continuation below the renal veins to above the level of the confluence of the common iliac veins. The patient underwent a complete resection of the mass, replacement of the IVC with Dacron graft, total hepatectomy and bilateral nephrectomy, with liver and kidney autotransplantation. Pathology was consistent with a high grade spindle cell sarcoma of vena cava origin. Patient was readmitted approximately 4 weeks postoperatively to begin adjuvant chemotherapy. This case represents a zone I-III IVC leiomyosarcoma treated with surgical R0 resection. This included a hepatectomy, bilateral nephrectomy, and hepatic and left renal autotransplantation. These complex tumors should be treated with surgical resection, and require a multidisciplinary approach. PMID- 26356494 TI - Treatment of Lyme neuroborreliosis with plasmapheresis. AB - Lyme disease is a rare tick-borne multisystemic infection caused by Borrelia burgdorferi. Different neurological conditions were reported in the disease. In this article, we present a 15-year-old patient hospitalized with ataxia who was diagnosed with Lyme neuroborreliosis. Intravenous immunoglobulin and ceftriaxone treatment was applied to the patient for 4 weeks. However, ataxia did not recover, upper and lower muscle weakness developed, and deep tendon reflexes diminished during follow-up. The patient was diagnosed with Guillain-Barre syndrome arising from B. burgdorferi. Second dose of intravenous immunoglobulin treatment was started for 5 days but the patient didn't recover. Therefore administration of plasmapheresis was decided. All symptoms relieved following the plasmapheresis. The effect of plasmapheresis in pediatric neuroborreliosis has not been documented before. This study highlights that plasmapheresis could be a useful alternative for pediatric neuroborreliosis cases. J. Clin. Apheresis 31:476-478, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26356495 TI - Prevalence of orofacial dysfunction in cerebral palsy and its association with gross motor function and manual ability. AB - AIM: To investigate the prevalence of orofacial dysfunction (OFD) and explore factors associated with OFD in young individuals with cerebral palsy (CP). METHOD: We conducted a cross-sectional study on a population with CP in a Swedish county (132 individuals, mean age 14y 2mo [SD 4y 5mo], range 5-22y) using the Nordic Orofacial Test - Screening (NOT-S), Gross Motor Function Classification System (GMFCS), and Manual Ability Classification System (MACS). The NOT-S interview was completed by 129 individuals (76 males, 53 females) of whom 52 (30 males, 22 females) also agreed to complete the NOT-S examination. RESULTS: OFD occurred in at least one NOT-S domain in about 80% of the individuals and was present in all subdiagnoses, GMFCS levels, and MACS levels. Prevalence of OFD increased with increasing levels of GMFCS and MACS from level I=55% to level V=100%. Within the 12 NOT-S domains, the prevalence of OFD varied between 19% and 69%, wherein seven of them were at least 40%: 'Drooling', 'Nose breathing', 'Chewing and swallowing', 'Face at rest', 'Oral motor function', 'Speech', and 'Facial expression' (in ascending order). INTERPRETATION: OFD is common in CP. The use of OFD screening in health service planning would assist detection of areas in need of further evaluation. PMID- 26356498 TI - Peripherally Silylated Porphyrins. AB - Silylation of peripherally lithiated porphyrins with silyl electrophiles has realized the first synthesis of a series of directly silyl-substituted porphyrins. The meso-silyl group underwent facile protodesilylation, whereas the beta-silyl group was entirely compatible with standard work-up and purification on silica gel. The meso-silyl group caused larger substituent effects to the porphyrin compared with the beta-silyl group. Silylation of beta-lithiated porphyrins with 1,2-dichlorodisilane furnished beta-to-beta disilane-bridged porphyrin dimers. A doubly beta-to-beta disilane-bridged Ni(II)-porphyrin dimer was also synthesized from a beta,beta-dilithiated Ni(II)-porphyrin and characterized by X-ray crystallographic analysis to take a steplike structure favorable for interporphyrinic interaction. Denickelation of beta-silylporphyrins was achieved upon treatment with a 4-tolylmagnesium bromide to yield the corresponding freebase porphyrins. PMID- 26356499 TI - Divergent Gold(I)-Catalyzed Skeletal Rearrangements of 1,7-Enynes. AB - The gold(I) complex catalyzed cycloisomerization and skeletal rearrangement of 1,n-enynes (n=5-7) is a powerful methodology for the efficient synthesis of complex molecular architectures. In contrast to 1,6-enynes, readily accessible homologous 1,7-enynes are largely unexplored in such transformations. Here, the divergent skeletal rearrangement of all-carbon 1,7-enynes by catalysis with a cationic gold(I) complex is reported. Depending on electronic and steric factors, differently substituted 1,7-enynes react via different carbocations formed from a common gold carbene intermediate to yield on the one hand novel exocyclic allenes and on the other hand tricyclic hexahydro-anthracenes through a novel dehydrogenative Diels-Alder reaction. PMID- 26356503 TI - Forecasting Bifurcations from Large Perturbation Recoveries in Feedback Ecosystems. AB - Forecasting bifurcations such as critical transitions is an active research area of relevance to the management and preservation of ecological systems. In particular, anticipating the distance to critical transitions remains a challenge, together with predicting the state of the system after these transitions are breached. In this work, a new model-less method is presented that addresses both these issues based on monitoring recoveries from large perturbations. The approach uses data from recoveries of the system from at least two separate parameter values before the critical point, to predict both the bifurcation and the post-bifurcation dynamics. The proposed method is demonstrated, and its performance evaluated under different levels of measurement noise, with two ecological models that have been used extensively in previous studies of tipping points and alternative steady states. The first one considers the dynamics of vegetation under grazing; the second, those of macrophyte and phytoplankton in shallow lakes. Applications of the method to more complex situations are discussed together with the kinds of empirical data needed for its implementation. PMID- 26356502 TI - Model-Based Quantification of the Systemic Interplay between Glucose and Fatty Acids in the Postprandial State. AB - In metabolic diseases such as Type 2 Diabetes and Non-Alcoholic Fatty Liver Disease, the systemic regulation of postprandial metabolite concentrations is disturbed. To understand this dysregulation, a quantitative and temporal understanding of systemic postprandial metabolite handling is needed. Of particular interest is the intertwined regulation of glucose and non-esterified fatty acids (NEFA), due to the association between disturbed NEFA metabolism and insulin resistance. However, postprandial glucose metabolism is characterized by a dynamic interplay of simultaneously responding regulatory mechanisms, which have proven difficult to measure directly. Therefore, we propose a mathematical modelling approach to untangle the systemic interplay between glucose and NEFA in the postprandial period. The developed model integrates data of both the perturbation of glucose metabolism by NEFA as measured under clamp conditions, and postprandial time-series of glucose, insulin, and NEFA. The model can describe independent data not used for fitting, and perturbations of NEFA metabolism result in an increased insulin, but not glucose, response, demonstrating that glucose homeostasis is maintained. Finally, the model is used to show that NEFA may mediate up to 30-45% of the postprandial increase in insulin-dependent glucose uptake at two hours after a glucose meal. In conclusion, the presented model can quantify the systemic interactions of glucose and NEFA in the postprandial state, and may therefore provide a new method to evaluate the disturbance of this interplay in metabolic disease. PMID- 26356504 TI - Can Text Messages Increase Empathy and Prosocial Behavior? The Development and Initial Validation of Text to Connect. AB - To what extent can simple mental exercises cause shifts in empathic habits? Can we use mobile technology to make people more empathic? It may depend on how empathy is measured. Scholars have identified a number of different facets and correlates of empathy. This study is among the first to take a comprehensive, multidimensional approach to empathy to determine how empathy training could affect these different facets and correlates. In doing so, we can learn more about empathy and its multifaceted nature. Participants (N = 90) were randomly assigned to receive either an empathy-building text message program (Text to Connect) or one of two control conditions (active versus passive). Respondents completed measures of dispositional empathy (i.e. self-perceptions of being an empathic person), affective empathy (i.e. motivations to help, immediate feelings of empathic concern), and prosocial behavior (i.e. self-reports and observer reports) at baseline, and then again after the 14 day intervention period. We found that empathy-building messages increased affective indicators of empathy and prosocial behaviors, but actually decreased self-perceptions of empathy, relative to control messages. Although the brief text messaging intervention did not consistently impact empathy-related personality traits, it holds promise for the use of mobile technology for changing empathic motivations and behaviors. PMID- 26356505 TI - Polyphosphate as a metabolic fuel in Metazoa: A foundational breakthrough invention for biomedical applications. AB - In animals, energy-rich molecules like ATP are generated in the intracellular compartment from metabolites, e.g. glucose, taken up by the cells. Recent results revealed that inorganic polyphosphates (polyP) can provide an extracellular system for energy transport and delivery. These polymers of multiple phosphate units, linked by high-energy phosphoanhydride bonds, use blood platelets as transport vehicles to reach their target cells. In this review it is outlined how polyP affects cell metabolism. It is discussed that polyP influences cell activity in a dual way: (i) as a metabolic fuel transferring metabolic energy through the extracellular space; and (ii) as a signaling molecule that amplifies energy/ATP production in mitochondria. Several metabolic pathways are triggered by polyP, among them biomineralization/hydroxyapatite formation onto bone cells. The accumulation of polyP in the platelets allows long-distance transport of the polymer in the extracellular space. The discovery of polyP as metabolic fuel and signaling molecule initiated the development of novel techniques for encapsulation of polyP into nanoparticles. They facilitate cellular uptake of the polymer by receptor-mediated endocytosis and allow the development of novel strategies for therapy of metabolic diseases associated with deviations in energy metabolism or mitochondrial dysfunctions. PMID- 26356506 TI - Repeated Witnessing of Conspecifics in Pain: Effects on Emotional Contagion. AB - Witnessing of conspecifics in pain has been shown to elicit socially triggered freezing in rodents. It is unknown how robust this response is to repeated exposure to a cage-mate experiencing painful stimulation. To address this question, shock-experienced Observer rats repeatedly witnessed familiar Demonstrators receive painful footshocks (six sessions). Results confirm that Observers freeze during the first testing session. The occurrence of this behaviour however gradually diminished as the experimental sessions progressed, reaching minimal freezing levels by the end of the experiments. In contrast, the appearance and continuous increase in the frequency of yawning, a behavior that was inhibited by metyrapone (i.e,. a glucocorticoid synthesis blocker), might represent an alternative coping strategy, suggesting that the observer's reduced freezing does not necessarily indicate a disappearance in the affective response to the Demonstrator's distress. PMID- 26356507 TI - Appendiceal Goblet Cell Carcinoids: Management Considerations from a Reference Peritoneal Tumour Service Centre and ENETS Centre of Excellence. AB - BACKGROUND: Appendix goblet cell carcinoids are known to share histological features of adenocarcinoma and neuroendocrine tumours. Due to their low incidence, quality evidence is lacking for the management of these patients. METHODS: We performed a single-centre retrospective study of patients with a confirmed diagnosis of appendiceal goblet cell carcinoid (GCC; 1996-2014). Patients were divided into curative intent (CI) and palliative intent (PI) cohorts. Our primary end point was overall survival (OS). RESULTS: Seventy-four patients were eligible; 76% were treated with CI [surgery only (36%), cytoreductive surgery (CRS) and hyperthermic intra-peritoneal chemotherapy (HIPEC; 36%), adjuvant chemotherapy (20%) and a combination of CRS and HIPEC followed by adjuvant chemotherapy (9%)], and 23% had advanced-stage disease amenable to palliative treatment (chemotherapy or supportive care) only. Completion right hemicolectomy, performed in 64% of the CI cohort, did not impact on the relapse rate or disease-free survival. FOLFOX chemotherapy was used in both the adjuvant and palliative settings; safety was as expected, and we observed a high rate (60%) of disease control in the palliative cohort. The estimated median OS (all patients), disease-free survival (CI patients) and progression-free survival (PI patients) were 52.1 (95% CI 29.4-90.3), 75.9 (26.6 not reached) and 5.3 (0.6-5.7) months, respectively. Age and stage were independent factors associated with OS in the multivariable analysis. Tang classification showed a trend for impact on OS. No benefit from specific adjuvant approach was identified; however, selection bias for treatment approach was observed. CONCLUSION: Prospective trials are needed to define optimal approaches in GCC. All GCC patients should be managed by specialized centres due to their esoteric behaviour; we provide management considerations based on our experience and conclusions. PMID- 26356508 TI - Recalibration of the HAS-BLED Score: Should Hemorrhagic Stroke Account for One or Two Points? AB - After a hemorrhagic stroke, it is uncertain whether this event scores one point (either for stroke or bleeding) or two points (one point each for stroke and bleeding) on the bleeding risk score termed HAS-BLED (hypertension, abnormal renal/liver function [one or two points], stroke, bleeding history or predisposition, labile international normalized ratio [INR], elderly [> 65 years], drugs/alcohol concomitantly [one or two points]). We investigated the value of a recalibration of the HAS-BLED score to account for two points from a hemorrhagic stroke. Data were analyzed from the Danish nationwide cohort of patients with incident atrial fibrillation (AF) from January 1999 to December 2013. The primary outcome in this observational study was major bleeding. The original and the recalibrated HAS-BLED scores were assessed, and the event rates of major bleeding were calculated. The predictive accuracy of major bleeding was compared by using C-statistics, the net reclassification index (NRI), and integrated discrimination improvement (IDI). An event rate for major bleeding of 4.3 per 100 person-years was recorded in the 210,299 patients with AF. The C statistics for the two scores were modest: 0.613 (95% CI, 0.607-0.619) for the original score and 0.616 (95% CI, 0.610-0.622) for the recalibrated score. The NRI was 10.0% (95% CI, 7.6-12.4). The relative IDI was 23.6% (95% CI, 15.7-31.5), reflecting that the recalibrated HAS-BLED score more accurately predicted bleeding events. Recalibration of the "S" component in the HAS-BLED score (counting two points for a hemorrhagic stroke) resulted in an increase in the C statistics, NRI, and IDI. This approach could potentially aid physicians in more accurate assessments of bleeding risk in patients with AF. PMID- 26356509 TI - Autosomal Translocation Patient Who Experienced Premature Menopause: A Case Report. AB - Premature ovarian failure (POF) is a condition in which the ovarian functions of hormone production and oocyte development become impaired before the typical age for menopause. POF and early menopause are present in a broad spectrum of gonad dysgenesis, from a complete cessation of ovarian function to an intermittent follicle maturation failure. Actually POF has been identified as a genetic entity (especially chromosome X), but data on genetic factors of premature menopause are limited. Until now, several cases revealed that inactivation of X chromosomes has an effect on ages of premature menopause and females with balanced or unbalanced X-autosome translocations can have several reproductive problems. On the other hand, there have been a few data that was caused by autosome-autosome translocation can lead. Therefore we report a relevant case of POF with translocation between chromosomes 1 and 4. She had her first menstrual period at the age of 12, and after 7 years she stopped menstruation. Chromosomal analysis showed 46, XX, t (1;4) (p22.3;q31.3). While evaluating this rare case, we could review various causes (especially genetic factors) of POF. To remind clinicians about this disease, we report a case of POF caused by autosome-autosome translocation with a literature review. PMID- 26356510 TI - [Surgical treatment of cerebral vascular diseases]. AB - Theoretical and practical aspects of the complex treatment of brain and spinal vascular diseases using microsurgical, endovascular and radiosurgical methods are considered. Authors present the data demonstrating that, due to the implementation of the program of development of vascular centers in the Russian Federation, considerable progress was made in the treatment of cerebral aneurisms and hemorrhagic stroke. In author's opinion, wide introduction of surgical methods in the treatment of occlusive lesions of the blood vessels supplying the brain is needed. PMID- 26356511 TI - [Variants of changes in the psychopathological phenomenology of the long-term remission in stable patients with attack-like progressive form of schizophrenia: a longitudinal study]. AB - AIM: An analysis of literature data on schizophrenia shows the change of interest from acute psychosis to phenomenology of remission. The separate objects of research become the impact of symptoms, observed in remission, on everyday life of patients and factors, which influence rapidity and comprehension of reintegration of patients into society. Authors aimed to describe the changes in psychopathological phenomenology and personality functioning during long-term (no less than three years) remission in patients with schizophrenia treated with atypical antipsychotics. MATERIAL AND METHODS: One hundred and thirty stable patients with schizophrenia underwent regular clinical examination during no less than three years. All patients were constantly medicated with atypical antipsychotics. RESULTS: Long-term observation of patients with the similar diagnosis and phase of disease, similar treatment and good treatment response (at least without psychotic exacerbation during the observation period) and tolerability revealed difference in changes of psychopathological phenomenology and personality functioning, which could be grouped into four distinct variants. The description of specificity of each variant is presented. A role of the initial level of personality functioning and its changes during observation period were analyzed. A new concept is introduced in order to name the ability of patients to use rationally recourses, delivered by treatment. The connection of this concept with the level of personality functioning was demonstrated. The hypothesis of mechanisms which underlie the four variants is offered. CONCLUSION: Long-term observation of the changes in the psychopathological phenomenology in the period of disease reveals the variants of the development of remission. The fluctuation of adaptive and regressive phases is registered. More objective factors, which impact on prognosis, are elucidated. PMID- 26356512 TI - [Mental disorders and new opportunities to identify suicide risk in children and adolescents with disabiliting diseases]. AB - AIM: To study mental health of children and adolescents with disabiliting diseases and comorbid mental disorders and to develop an instrument for assessment suicide risk. MATERIAL AND METHODS: The structure of mental disorders in 800 students of correctional schools with disabilities, who have disabiliting diseases (somatoneurological, musculoskeletal, sensory impairment, intellectual disorders), was studied. RESULTS AND CONCLUSION: The prevalence of mental disorders was 83.5%. The highest prevalence was observed for developmental disorders, mental retardation and disorders due to damage or brain dysfunction. High levels of anxiety were found in 33%. There were difficulties in the diagnosis of emotional disorders and signs of suicidal behavior in adolescents with disabiliting diseases and comorbid disorders of psychological development. To detect the signs of suicidal behavior, authors have developed a clinical questionnaire for assessment of suicide risk in people of this category. The results of the screening are presented. PMID- 26356513 TI - [Statokinetic characteristics of vestibular dysfunction in patients with vascular compression of the cochleo-vestibular nerve]. AB - AIM: To study the state of statokinetic stability in patients with recurrent vestibular dysfunction caused by the vascular compression of the cochlea vestibular nerve. MATERIAL AND METHODS: Authors examined 30 patients with recurrent vestibular dysfunction in which neuroimaging studies revealed the vessel adjacent to the cochlea-vestibular nerve. Statokinetic stability evaluation was selected as a neurophysiological indicator of the cochlea vestibular nerve hyperactivity syndrome. RESULTS AND CONCLUSION: The correlation of the statokinetic stability indicators with the functional tests used and the side of the vascular compression of the cochlea-vestibular nerve has demonstrated high sensitivity of the statokinetic function to the turning of the head to the side of the neurovascular interaction with the decrease in stability in 17 (77.3%), as well as the minor in 15 (68.2%) and marked in 7 (31,8%) cases worsening of the statokinetic function during optokinetic stimulation (p<0.05). High diagnostic value of computer stabilometry with biological feedback in the objectification of the vestibulovegetative syndrome and detection of latent vestibular dysfunction in the patients with proven vascular compression of the cochlea-vestibular nerve has been shown. PMID- 26356514 TI - [Clinical syndromes of neurotransmitter system dysfunction in severe brain injury]. AB - AIM: To explore neurotransmitter system dysfunctions involved in maintaining of consciousness and motor functions in patients with severe traumatic brain injury (TBI) and to assess their severity and predictive value. MATERIAL AND METHODS: Authors examined 100 patients (34 women and 66 men), aged 32.0 +/- 13.0 years, with severe TBI. Eighty-eight patients (31 women and 57 men) were studied in the acute stage (1-15 days, mean 5.8 +/- 3.7 days) and 70 patients (24 women and 46 men) in the subacute stage (18-70 days, mean 30.4 +/- 12.7 days). Inclusion criteria were: severe TBI with depression of consciousness (<= 7 scores on the Glasgow Coma Scale), admission to the hospital in acute and subacute stages. Outcome of TBI was evaluated using the Glasgow Outcome Scale. RESULTS AND CONCLUSION: The following clinical syndromes of neurotransmitter system dysfunction were singled out: excess or insufficiency of glutamate, cholinergic deficit, excess or insufficiency of dopamine. Their transformation during disease was identified. Predictive value of neurotransmitter dysfunctions for TBI is emphasized. PMID- 26356515 TI - [Remote consequences of the long-term uncontrollable consumption of anxiolytics and hypnotics in elderly: a problem of drug dependence]. AB - AIM: To identify main clinical/psychopathological characteristics of aged psychiatric inpatients who regularly used anxiolytic and hypnotic benzodiazepines without control from the physician. MATERIAL AND METHODS: Authors examined 56 women over 50 years hospitalized due to a psychiatric disorder. Before admission, they regularly used benzodiazepines without a prescription for more than 2 months. The patients were studied during 4 weeks in the hospital. To assess the severity and dynamics of their condition, we administered psychopathological analysis and common psychometric scales as well as our own version of the scale for benzodiazepine dependence. RESULTS AND CONCLUSION: The diagnosis of drug dependence was based on the three criteria: symptoms of pathological dependence of benzodiazepine, benzodiazepine withdrawal syndrome with severe somatic/autonomic symptoms and exacerbation of dependence, increase in tolerability to benzodiazepine anxiolytics and hypnotics; 64.3% of the patients met these criteria. An analysis of risk factors for this disease in elderly demonstrated the higher risk in patients aged <= 60 years and in those who used diazepam. The risk was higher in patients who preferred phenazepam. PMID- 26356516 TI - [Eating disorders in psychiatric patients during treatment with second generation antipsychotics]. AB - AIM: To identify the frequency and characteristics of eating disorders in patients with schizophrenia treated with second generation antipsychotics. MATERIAL AND METHODS: A sample included 56 patients (48 women and 8 men, mean age 28 +/- 4.5 years) with schizophrenia and schizoaffective disorder. Patients received risperidone, quetiapine and olanzapine. The study employed clinical anamnestic, endocrinological methods and assessment of eating behavior with DEBQ (The Dutch Eating Behavior Questionnaire). All of the patients had extra Body mass or obesity: extra Body mass of the 1st grade was found in 18 patients (BMI<30 kg/m2) and obesity grade 2-3 in 38 patients (BMI>30 kg/m2). RESULTS AND CONCLUSION: Authors identified different types of eating disorders: external, restrictive and emotiogenic as well as the relationship of their prevalence and severity with sex, drug, presence and grade of obesity. Based on these RESULTS: we developed recommendations for management of patients treated with second generation antipsychotics. PMID- 26356517 TI - [New possibilities to increase the results of posttraumatic nerve regeneration with sympathectomy]. AB - AIM: To study the influence of sympathectomy on nerve regeneration in human extremities. MATERIAL AND METHODS: Autoneuroplasty was performed in 86 patients with posttraumatic defects of median and ulnar nerves: in 42 cases in combination with sympathectomy (thoracoscopic clipping of Th3-4 sympathetic ganglions) and in 44 cases without sympathectomy. Computer thermography, laser Doppler flowmetry with spectral wavelet-analysis of blood flow oscillations, ultrasonography of nerve trunks and stimulation electroneuromyography were used. RESULTS AND CONCLUSION: Induced sympathectomy was for the first time shown to have a positive activating influence on the restoration of innervation and tissue trophics in the course of posttraumatic nerve regeneration. The combination of autoneuroplasty with induced sympathectomy contributes to a more complete restoration of motor and sensory nerve fibers, helps to normalize the blood flow in the microvascular bed and thermal topography of the damaged segment of the extremity and support the trophotropic direction of tissue control including the previously denervated area. PMID- 26356518 TI - [Characteristics of ischemic stroke according to hospital register data: a role of neuroreparative therapy]. AB - AIM: To study characteristics of the acute stage of ischemic stroke (IS) basing on the data of a hospital register of the Perm Regional vascular center and to assess the efficacy and safety of the drug cellex in patients with IS. MATERIAL AND METHODS: Authors have analyzed the group of 128 patients with MRI-confirmed acute ischemic lesion. The subgroup of 40 patients, which beside the basic therapy received cellex in dose of 0.1 mg during 10 days, was randomized. RESULTS: The following data were analyzed: gender and age, prevalence of risk factors, primary prevention, time before admission, clinical presentations, results of instrumental diagnostic methods, pathogenic structure of stroke, use of intravenous thrombolysis, regimens of secondary prevention, functional outcome and its predictors. CONCLUSION: The group of patients was characterized by the high prevalence of risk factors, insufficient primary prevention, prolonged time before the admission, low rate of thrombolysis use and significant prevalence of large artery disease associated with stroke. The main independent predictors of low mobility level at discharge were severe neurological deficit on admission, cognitive impairment and age. Patients treated with cellex were characterized by the lower level of neurologic deficit, higher mobility and better global cognitive status in comparison with controls. PMID- 26356519 TI - [Facial pain]. AB - Diagnosis and treatment of facial pain is a problem for physicians of different specialties (neurologists, dentists, surgeons, oculists, otolaryngologists and psychiatrists). A classification of this pathology is far from ideal and an interdisciplinary comprehensive approach is needed. Current approaches to etiotropic, symptomatic and pathogenetic treatment of patients with most frequent variants of orofacial pain are presented. PMID- 26356520 TI - [The study of the efficacy of Botulinum toxin type A in patients with poststroke upper-limb spasticity ULIS-II: an analysis of Russian patients]. AB - AIM: To assess the efficacy of Botulinum toxin type A (BoNT-A) injections in routine practice. MATERIAL AND METHODS: An international, post-marketing, multi center, observational, prospective, longitudinal study included patients >=18 years with poststroke upper-limb spasticity in whom a decision to inject BoNT-A had already been made, and who had no previous treatment with BoNT-A or BoNT-B within the last 12 weeks. The responder rate was assessed by the patient-centered goal attainment scaling (GAS). RESULTS AND CONCLUSION: The study included 7 Russian research centers (41 patients). Sixteen patients (39%) received BoNT-A injections prior to entering the study. During the treatment, 29 patients (70.7%) received dysport injections; 2 (4.9%) botox injections, 8 (19.5%) xeomin injections and 2 (4.9%) other BoNT-A agents. The primary treatment goals were successfully attained in 87.8%, secondary treatment goals in 88.3%. An improvement in passive function as primary goal and as secondary goal were achieved in 100%, in the range of movement in 94.9%, pain reduction in 82.4%, improvement in active function of the upper limb in 76.5%, reduction in involuntary movements (associated reactions) in 83.3% of cases. Investigators' global assessment of benefits revealed that 97.6% of patients showed positive effects from BoNT-A injections. Pateitnts' assessment of global benefits was slightly lower - 90,2% of patients reported positive treatment effects When assessed by patients, the rate of global benefits was 90.2%. Botulinum-toxin therapy is an effective treatment option. In the vast majority of patients, it allows both for reduction in muscle tone and functional benefits that could improve quality of life of the patients. PMID- 26356521 TI - [Clinical and electroencephalographic characteristics of specific language impairment in children and an evaluation of the efficacy of cerebrolysin]. AB - To study different forms of specific language impairment in children and to evaluate the efficacy of cerebrolysin in clinical and electroencephalographic aspects. MATERIAL AND METHODS: Authors examined 60 children, aged 5-7 years, with a specific language impairment (SLI). RESULTS AND CONCLUSION: The study showed the significantly higher severity of speech disorders, a higher degree of asthenia and dyspraxia/dysgnosia in a group of children with a disorder of receptive language (SLI-R) compared to children with a disorder of expressive speech (SLI-E). A comparative analysis of the EEG power spectra showed large values of slow theta-band EEG in children with SLI compared with healthy children. Children with SLI-R were characterized by the increase in theta rhythm power in the occipital region compared with children with SLI-E. The high efficacy of cerebrolysin in the treatment of this disease (an improvement was obtained in 73.3% of cases) was demonstrated, with the best effect in children with SLI-E (80.0% of cases). PMID- 26356522 TI - [Parameters of electroneuromyography of lower extremities and densitometry in osteochondrosis of lumbar spine]. AB - AIM: To study the density of bone tissue and parameters of electroneuromyography (ENMG) in patients with osteochondrosis of lumbar spine. MATERIAL AND METHODS: Authors examined 67 patients, mean age 41 years, diagnosed with unilateral lumbar ischialgia syndrome. RESULTS AND CONCLUSION: The changes in the density of bone tissue (osteopenia and osteoporosis) and marked disturbances of neuromuscular apparatus function were found in 79% of the patients. This finding suggests the relationship between the ENMG and densitometry parameters. PMID- 26356523 TI - [Violation of cerebral hemodynamics in the cardiac dysfunction caused by chronic heart failure]. AB - OBJECTEVE: To study changes of cerebral haemo dynamics at the progressing kardialny dysfunction caused by chronic heart failure. MATERIAL AND METHODS: Authors executed all researches on male Wistar rats. Used methods: echocardiography and ultrasound Doppler study of the brain vessels is performed using US-apparatus Mindray M5, using linear sensor 10 MHz (Mindray, China); magnetic resonance imaging of brain and heart of experimental animals with chronic heart failure. Applied functional tests. RESULTS: In the early stage of cardiac decompensation does not change the blood flow in the carotid and basilar arteries, but seizure readiness (SR) of the animals increased. Preservation of reactivity to hypercapnic and compression tests, suggests that the increase in SR is not associated with circulatory disorders in the brain. Exacerbation of heart failure (HF) leads to severe decompensation, including a decrease in blood flow in the carotid and basilar arteries. Metabolic cascade of autoregulation in these animals areaktiven and myogenic greatly reduced. In this case revealed a progressive increase in the SR. CONCLUSION: Inefficiency of the heart at different stages of HF is not the same effect on the reserves of the autoregulation of cerebral hemodynamics, which affects the formation and aggravation of SR. Moreover, its rise in various stages of decompensation is not always caused by cerebral ischemia. PMID- 26356524 TI - [Characteristics of the regulation of neurotrophic mechanisms in ischemic stroke]. AB - AIM: To explore the endogenous and pharmacological activation of neurotrophic mechanisms in a model of brain ischemic lesion in rats. MATERIAL AND METHODS: The study was performed on 170 male albino rats (195-205 g). The model of ischemic stroke was accomplished by the electrocoagulation of the proximal segment of the left middle cerebral artery and simultaneous permanent ligation of the left common carotid artery. RESULTS AND CONCLUSION: The evaluation of NSE, NO, VEGF, NGF levels in the brain cytoplasmic lysate and plasma showed the delayed activation of neurotrophic mechanisms in astrocytes accompanied by a decrease in delayed alteration of neurons. The use of cytoflavin in the treatment of stroke was accompanied by the earlier and more intense activation of neurotrophic mechanisms in astrocytes, delayed activation of neurotrophic mechanisms in endothelial cells, which promoted neuroprotection in acute ischemic stroke. PMID- 26356525 TI - [Conservative and surgical treatment of patients with resistant epilepsy]. AB - AIM: To optimize drug treatment in early (6 months) and late (up to 3 years) stages of postoperative period and to study its efficacy. MATERIAL AND METHODS: There were selected 72 patients with resistant epilepsy and epileptic encephalopathy symptoms from 467 patients operated for epilepsy. RESULTS: By the end of a 3-year follow-up observation, we found the reduction in seizure frequency and seizure control in 66.3% of patients; regression of EEG paroxysmal activity in 56.8% and reduction in mental disorder symptoms (anxiety and depression) in 12.7%. CONCLUSION: The data obtained substantiate the necessity to optimize antiepileptic and pathogenetic drug treatment of patients with resistant epilepsy and encephalopathy symptoms during the 3-year postoperative period. PMID- 26356526 TI - [Genetic aspects of migraine]. AB - Migraine is a common disease characterized by severe headache with nausea, vomiting and hypersensitivity to sounds, light, smell. Neurological symptoms during aura period develop in 25% of patients. Genes responsible for migraine development have been identified. The mutations in familial hemiplegic migraine are better investigated. The serotonin system plays a key role in the migraine pathogenesis. It was described the syndrome of migraine-like headache occurring due impaired serotonin metabolism in patients with celiac disease. Celiac disease is a chronic polysyndrome disease, enteropathy. Arteriopathies associated with migraine are cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (syndrome CADASIL), retinal vasculopathy with cerebral leukodystrophy (RVCL), hereditary systemic angiopathy (HSA), mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS). PMID- 26356527 TI - [Oxidative stress and Parkinson's disease: mechanisms and perspectives of treatment]. PMID- 26356528 TI - [Depression in alcohol addicted patients]. AB - In this review, authors considered characteristics of depression and alcohol addiction. Depressive disorders comorbid to alcoholism are heterogeneous in their nature and structure and can be observed during alcohol withdrawal syndrome and in remission. Antidepressants, and first of all selective serotonin reuptake inhibitors (SSRIs), along with the specific anti-relapse drugs (disulfiram, acamprosate and naltrexone), are the drugs of choice in treatment of alcohol addiction. Efficient combinations of pharmacotherapy and psychotherapy can improve outcomes of both comorbid disorders. PMID- 26356529 TI - [Intellectual and emotional characteristics of some European nations in relation to the stages of their historical development]. AB - Intellectual and emotional characteristics of some European nations in the aspect of their historical development are illustrated by the example of representatives of British and Italian culture. Behavior, mentality and other speech-related functions are analyzed. PMID- 26356530 TI - Insulin and mTOR Pathway Regulate HDAC3-Mediated Deacetylation and Activation of PGK1. AB - Phosphoglycerate kinase 1 (PGK1) catalyzes the reversible transfer of a phosphoryl group from 1, 3-bisphosphoglycerate (1, 3-BPG) to ADP, producing 3 phosphoglycerate (3-PG) and ATP. PGK1 plays a key role in coordinating glycolytic energy production with one-carbon metabolism, serine biosynthesis, and cellular redox regulation. Here, we report that PGK1 is acetylated at lysine 220 (K220), which inhibits PGK1 activity by disrupting the binding with its substrate, ADP. We have identified KAT9 and HDAC3 as the potential acetyltransferase and deacetylase, respectively, for PGK1. Insulin promotes K220 deacetylation to stimulate PGK1 activity. We show that the PI3K/AKT/mTOR pathway regulates HDAC3 S424 phosphorylation, which promotes HDAC3-PGK1 interaction and PGK1 K220 deacetylation. Our study uncovers a previously unknown mechanism for the insulin and mTOR pathway in regulation of glycolytic ATP production and cellular redox potential via HDAC3-mediated PGK1 deacetylation. PMID- 26356531 TI - Parting ways: parasite release in nature leads to sex-specific evolution of defence. AB - We evaluated the extent to which males and females evolve along similar or different trajectories in response to the same environmental shift. Specifically, we used replicate experimental introductions in nature to consider how release from a key parasite (Gyrodactylus) generates similar or different defence evolution in male vs. female guppies (Poecilia reticulata). After 4-8 generations of evolution, guppies were collected from the ancestral (parasite still present) and derived (parasite now absent) populations and bred for two generations in the laboratory to control for nongenetic effects. These F2 guppies were then individually infected with Gyrodactylus, and infection dynamics were monitored on each fish. We found that parasite release in nature led to sex-specific evolutionary responses: males did not show much evolution of resistance, whereas females showed the evolution of increased resistance. Given that male guppies in the ancestral population had greater resistance to Gyrodactylus than did females, evolution in the derived populations led to reduction of sexual dimorphism in resistance. We argue that previous selection for high resistance in males constrained (relative to females) further evolution of the trait. We advocate more experiments considering sex-specific evolutionary responses to environmental change. PMID- 26356533 TI - Efficient charge-transport in hybrid lead iodide perovskite solar cells. AB - Recently, highly efficient solar cells based on organic-inorganic perovskites have been intensively studied for developing fabricating methods and device structures. To improve the performance of perovskite film devices, delicate control of charge transfer material interconnectivity is required. Here, controlling the mesoporous TiO2 structure improves their charge collection and injection rate, and allows substantial enhancement of the corresponding device performance. We found that increasing the TiCl4 processing time deteriorates the device performance by introducing a large amount of excessively large perovskite particles, surface roughness and charge recombination. Proper TiCl4 processing dramatically improves the charge transport within the electron transfer layer, explaining the efficient performance of meso-superstructured solar cells. PMID- 26356534 TI - Erratum: Primary Biliary Cirrhosis and Primary Sclerosing Cholangitis: a Review Featuring a Women's Health Perspective: The JCTH staff. PMID- 26356535 TI - Glutamine Assimilation and Feedback Regulation of L-acetyl-N-glutamate Kinase Activity in Chlorella variabilis NC64A Results in Changes in Arginine Pools. AB - Glutamine is a metabolite of central importance in nitrogen metabolism of microorganisms and plants. The Chlorella PII signaling protein controls, in a glutamine-dependent manner, the key enzyme of the ornithine/arginine biosynthesis pathway, N-acetyl-L-glutamate kinase (NAGK) that leads to arginine formation. We provide evidence that glutamine promotes effective growth of C. variabilis strain NC64A. The present study shows that externally supplied glutamine directly influences the internal pool of arginine in NC64A. Glutamine synthetase (GS) catalyzes the ATP-dependent conversion of glutamate and ammonium to glutamine. The results of this study demonstrate that glutamine acts as a negative effector of GS activity. These data emphasize the importance of glutamine-dependent coupling of metabolism and signaling as components of an efficient pathway allowing the maintenance of metabolic homeostasis and sustaining growth of Chlorella. PMID- 26356536 TI - Identifying the causal mechanisms of the quiet eye. AB - Scientists who have examined the gaze strategies employed by athletes have determined that longer quiet eye (QE) durations (QED) are characteristic of skilled compared to less-skilled performers. However, the cognitive mechanisms of the QE and, specifically, how the QED affects performance are not yet fully understood. We review research that has examined the functional mechanism underlying QE and discuss the neural networks that may be involved. We also highlight the limitations surrounding QE measurement and its definition and propose future research directions to address these shortcomings. Investigations into the behavioural and neural mechanisms of QE will aid the understanding of the perceptual and cognitive processes underlying expert performance and the factors that change as expertise develops. PMID- 26356532 TI - Discovery of Molecular Therapeutics for Glaucoma: Challenges, Successes, and Promising Directions. AB - Glaucoma, a heterogeneous ocular disorder affecting ~60 million people worldwide, is characterized by painless neurodegeneration of retinal ganglion cells (RGCs), resulting in irreversible vision loss. Available therapies, which decrease the common causal risk factor of elevated intraocular pressure, delay, but cannot prevent, RGC death and blindness. Notably, it is changes in the anterior segment of the eye, particularly in the drainage of aqueous humor fluid, which are believed to bring about changes in pressure. Thus, it is primarily this region whose properties are manipulated in current and emerging therapies for glaucoma. Here, we focus on the challenges associated with developing treatments, review the available experimental methods to evaluate the therapeutic potential of new drugs, describe the development and evaluation of emerging Rho-kinase inhibitors and adenosine receptor ligands that offer the potential to improve aqueous humor outflow and protect RGCs simultaneously, and present new targets and approaches on the horizon. PMID- 26356537 TI - Terrestrial Trophic Transfer of Bulk and Nanoparticle La2O3 Does Not Depend on Particle Size. AB - The bioaccumulation and trophic transfer of bulk and nanoparticle (NP) La2O3 from soil through a terrestrial food chain was determined. To investigate the impact of growth conditions, lettuce (Lactuca sativa) was grown in 350 or 1200 g of bulk/NP amended soil. Leaf tissues were fed to crickets (Acheta domesticus) or darkling beetles (Tenebrionoidea); select crickets were fed to mantises. In the small pot (350 g), La2O3 exposure reduced plant biomass by 23-30% and La tissue content did not differ with particle size. In the large pot (1200 g), biomass was unaffected by exposure and La content in the tissues were significantly greater with bulk particle treatment. Darkling beetles exposed to bulk and NP La2O3 contaminated lettuce contained La at 0.18 and 0.08 mg/kg; respectively (significantly different, P < 0.05). Crickets fed bulk or NP La2O3-exposed lettuce contained 0.53 and 0.33 mg/kg, respectively (significantly different, P < 0.05) with 48 h of depuration. After 7 d of depuration, La content did not differ with particle size, indicating that 48 h may be insufficient to void the digestive system. Mantises that consumed crickets from bulk and NP-exposed treatments contained La at 0.05-0.060 mg/kg (statistically equivalent). These results demonstrate that although La does trophically transfer, biomagnification does not occur and NP levels are equivalent or less than the bulk metal. PMID- 26356538 TI - Netgram: Visualizing Communities in Evolving Networks. AB - Real-world complex networks are dynamic in nature and change over time. The change is usually observed in the interactions within the network over time. Complex networks exhibit community like structures. A key feature of the dynamics of complex networks is the evolution of communities over time. Several methods have been proposed to detect and track the evolution of these groups over time. However, there is no generic tool which visualizes all the aspects of group evolution in dynamic networks including birth, death, splitting, merging, expansion, shrinkage and continuation of groups. In this paper, we propose Netgram: a tool for visualizing evolution of communities in time-evolving graphs. Netgram maintains evolution of communities over 2 consecutive time-stamps in tables which are used to create a query database using the sql outer-join operation. It uses a line-based visualization technique which adheres to certain design principles and aesthetic guidelines. Netgram uses a greedy solution to order the initial community information provided by the evolutionary clustering technique such that we have fewer line cross-overs in the visualization. This makes it easier to track the progress of individual communities in time evolving graphs. Netgram is a generic toolkit which can be used with any evolutionary community detection algorithm as illustrated in our experiments. We use Netgram for visualization of topic evolution in the NIPS conference over a period of 11 years and observe the emergence and merging of several disciplines in the field of information processing systems. PMID- 26356540 TI - Modified Balloon Protection Technique for Preoperative Embolization of Feeder Arteries from Internal Carotid Artery Branches to Skull-Base Tumor: Technical Note. AB - OBJECTIVE: To improve bleeding management during brain tumor surgery, feeder arteries supplying the tumor are often embolized presurgically. However, access to feeder arteries can be limited, and embolization of feeders from internal carotid artery (ICA) branches often causes complications. We evaluated the PercuSurge GuardWire (Medtronic, Minneapolis, Minnesota, United States) system (PGWS) with aspiration catheter as a modification of the embolization technique used to block tumor-supplying branches of the ICA. METHODS: Two skull-base tumors were treated with preoperative embolization. One was a meningioma; the other was a hemangiopericytoma. In each case, the microcatheter could not be threaded into the ICA feeder arteries. Therefore, particulate embolic material was injected near the ICA branch while maintaining ICA balloon protection by the PGWS at the orifice of the ophthalmic artery. After embolization, we removed the remaining embolic material in the ICA using an aspiration catheter. In both cases, there were no postembolization complications and no high-intensity areas in the diffusion-weighted magnetic resonance image, and the tumorectomy proceeded as scheduled. CONCLUSION: This modified technique may be a promising alternative for reducing embolic complications and improving the success rate, although case accumulation is needed to confirm this result. PMID- 26356541 TI - Effect of surface coating on the biocompatibility and in vivo MRI detection of iron oxide nanoparticles after intrapulmonary administration. AB - Superparamagnetic iron oxide nanoparticles (SPIONs) have attracted special attention as novel nanoprobes capable of improving both the therapy and diagnosis of lung diseases. For safe prospective clinical applications, their biocompatibility has to be assessed after intrapulmonary administration. This study was therefore conducted to understand the biological impact of SPIONs and their further surface-functionalization with polyethylene glycol (PEG) having either negative (i.e. carboxyl) or positive (i.e. amine) terminal in a 1-month longitudinal study following acute and sub-acute exposures. Noninvasive free breathing MR imaging protocols were first optimized to validate SPIONs detection in the lung and investigate possible subsequent systemic translocation to abdominal organs. Pulmonary Magnetic Resonance Imaging (MRI) allowed successful in vivo detection of SPIONs in the lung using ultra-short echo time sequence. Following high-dose lung administration, MR imaging performed on abdominal organs detected transient accumulation of SPIONs in the liver. Iron quantification using Inductive coupled plasma - Mass mass spectroscopy (ICP-MS) confirmed MRI readouts. Oxidative stress induction and genotoxicity were then conducted to evaluate the biocompatibility of SPIONs with their different formulations in a mouse model. A significant increase in lipid peroxidation was observed in both acute and sub-acute sets and found to regress in a time-dependent manner. PEG functionalized SPIONs revealed a lower effect with no difference between both terminal modifications. Genotoxicity assessments revealed an increase in DNA damage and gene expression of CCL-17 and IL-10 biomarkers following SPIONs administration, which was significantly higher than surface-modified nanoparticles and decreased in a time-dependent manner. However, SPIONs with carboxyl terminal showed a slightly prominent effect compared to amine modification. PMID- 26356539 TI - Human Mesenchymal Stem Cells Retain Multilineage Differentiation Capacity Including Neural Marker Expression after Extended In Vitro Expansion. AB - The suitability of human mesenchymal stem cells (hMSCs) in regenerative medicine relies on retention of their proliferative expansion potential in conjunction with the ability to differentiate toward multiple lineages. Successful utilisation of these cells in clinical applications linked to tissue regeneration requires consideration of biomarker expression, time in culture and donor age, as well as their ability to differentiate towards mesenchymal (bone, cartilage, fat) or non-mesenchymal (e.g., neural) lineages. To identify potential therapeutic suitability we examined hMSCs after extended expansion including morphological changes, potency (stemness) and multilineage potential. Commercially available hMSC populations were expanded in vitro for > 20 passages, equating to > 60 days and > 50 population doublings. Distinct growth phases (A-C) were observed during serial passaging and cells were characterised for stemness and lineage markers at representative stages (Phase A: P+5, approximately 13 days in culture; Phase B: P+7, approximately 20 days in culture; and Phase C: P+13, approximately 43 days in culture). Cell surface markers, stem cell markers and lineage-specific markers were characterised by FACS, ICC and Q-PCR revealing MSCs maintained their multilineage potential, including neural lineages throughout expansion. Co expression of multiple lineage markers along with continued CD45 expression in MSCs did not affect completion of osteogenic and adipogenic specification or the formation of neurospheres. Improved standardised isolation and characterisation of MSCs may facilitate the identification of biomarkers to improve therapeutic efficacy to ensure increased reproducibility and routine production of MSCs for therapeutic applications including neural repair. PMID- 26356542 TI - The effects of exercise using PNF in patients with a supraspinatus muscle tear. AB - [Purpose] The aim of this study was to examine the effects of proprioceptive neuromuscular facilitation techniques and simple exercise on subjective pain reduction and blood flow velocity in supraspinatus tear patients and to evaluate muscle recovery. [Subjects and Methods] The 20 subjects of this study were diagnosed with supraspinatus tears by MRI. The subjects have performed PNF techniques and Simple exercise for 12 weeks. [Results] After 12 weeks of proprioceptive neuromuscular facilitation techniques and simple exercise, the blood flow velocity, Visual Analogue Scale, and disabilities of the arm, shoulder, and hand score showed statistically significant difference. Also, the difference between the proprioceptive neuromuscular facilitation techniques and simple exercise was statistically significant. [Conclusion] In conclusion, 12 weeks of proprioceptive neuromuscular facilitation treatment and simple exercise therapy had no effect on pain reduction in patients with supraspinatus tear, but in terms of functionality, the proprioceptive neuromuscular facilitation treatment was effective. PMID- 26356543 TI - Morphologic clues and utility of fluorescence in situ hybridization for the diagnosis of nevoid melanoma. AB - BACKGROUND: Nevoid melanomas include melanomas with a low power silhouette similar to melanocytic nevi. However, at higher power magnification, nevoid melanoma may have severe nuclear atypia and dermal mitoses. METHODS: We performed a clinical, pathological and molecular study on a series of 58 examples of nevoid melanoma, excluding cases with spitzoid morphology. RESULTS: We identified distinct morphologic patterns: 'classic' nevoid melanoma, superficial spreading melanomas with nevoid invasive melanoma, lentigo maligna with nevoid invasive melanoma and deep penetrating nevus-like nevoid melanoma. Fluorescence in situ hybridization (FISH) was positive in 74% of cases. Copy number gains in 8q24 were common in amelanotic nevoid melanoma. The median follow-up was 28 months (range 140). At last follow-up, 37 patients had no evidence of disease, 3 were alive with metastases and 6 died from metastatic melanoma. Of these six patients who died, four had a sentinel lymph node biopsy (SLNB) performed, which was negative in all four. CONCLUSIONS: We describe distinct clues to the diagnosis of nevoid melanoma including occult intraepidermal atypia, and expansile nesting resulting in asymmetric silhouette or dermal papillae expansion. We also describe that nevoid melanoma have infrequent SLNB involvement in aggressive cases, and have frequent 8q24 gains rather than 9p21 deletions. Our results suggest that nevoid melanoma are distinct from spitzoid melanomas and should be distinguished. PMID- 26356544 TI - Activation of the gluteus medius according to load during horizontal hip abduction in a one-leg stance. AB - [Purpose] This study researched the influences of different loads on muscle activity of the posterior fibers of the gluteus medius in a one-leg standing position. [Subjects] Twenty-four healthy adult men participated in this study. [Methods] All participants performed the one-leg standing position under four conditions: the standard no-load condition, in which the non-weight-bearing leg was lifted and kept parallel to the back and then pelvic or lumbar rotation was performed without thorax rotation, and the 0 kg, 1 kg, and 3 kg load conditions, in which horizontal shoulder abduction was performed with a load of 0 kg, 1 kg, or 3 kg added to the hand. The electromyographic activity of the posterior fibers of the gluteus medius was measured using a wireless surface electromyography under all conditions. The electromyographic activity of each muscle under the four conditions during the one-leg stance was analyzed using one-way analysis of variance. [Results] The electromyographic activity of the posterior fiber of the gluteus medius was significantly increased under the 3 kg load condition compared with the no-load, 0 kg load, and 1 kg load conditions. [Conclusion] These findings indicated that muscle activation is affected by increases in load in the one-leg standing position. The load on the upper extremity influences the muscle activity of the contralateral lower extremity. PMID- 26356545 TI - Patient Characteristics, Safety, and Tolerability with Telaprevir Treatment for HCV in the Clinic: a Retrospective, Multicenter Study. AB - BACKGROUND AND AIMS: There is a paucity of information regarding similarities and differences between patients from the phase 3 studies of telaprevir and those receiving telaprevir in clinical practice. METHODS: This retrospective chart review evaluated baseline characteristics and follow-up safety and tolerability data for patients with hepatitis C virus (HCV) infection treated with telaprevir and peginterferon alfa and ribavirin (PR) in clinical practice. RESULTS: In total, 338 charts from patients at four academic and three community US treatment centers who received telaprevir and PR and had at least 12 weeks of follow-up data were included; 62% were from academic centers and 38% were from community centers. Of the 338 patients, 269 completed 12 weeks of telaprevir and PR; 32 discontinued due to adverse events. Mean age was 55 years; patients were predominantly white (79.3%) males (58.9%) with genotype 1a HCV infection (61.8%); 35.5% were reported to have cirrhosis at baseline; and 55.3% previously received PR. Hypertension and depression were the most common comorbidities. Patient characteristics outside the per-protocol minimum criteria used in the phase 3 studies of telaprevir were, e.g., hemoglobin, 9.2%; albumin, 5.3%; platelets, 11.5%; and neutrophil count, 5.6%. Adverse events occurred in 329/338 (97.3%) patients, with anemia, fatigue, nausea, and rash being the most common. Of 38 hospitalizations, 26 were deemed related to telaprevir and PR. Three patients died due to pneumonia, septic shock, and hepatorenal syndrome (n=1 each). CONCLUSIONS: These findings complement those reported from rigorous, randomized controlled studies with telaprevir-based treatment and provide a general assessment of similarities and/or differences between patients from the phase 3 studies of telaprevir and those treated with telaprevir in clinical practice. PMID- 26356546 TI - Violet Fox: A Clinical View of Vertebral Fractures. AB - Had Violet's abdominal MR not been performed, or its findings not appreciated, the cause of her clinical event might never have been known because our current concept of osteoporotic vertebral fracture (VF) is substantially predicated on a change in either vertebral height or shape on lateral or sagittal spine imaging. The intention of this commentary is to stimulate a multidisciplinary conversation of osteoporotic VFs from an integrated clinical, physiological, and imaging perspective. For research and epidemiological purposes, osteoporotic VFs have been defined as a reduction in anterior, middle, or posterior vertebral height although the required minimum height reduction (e.g., 15% or 20%) varies among definition schemes. We further classify osteoporotic VFs to be "clinical" when they are accompanied by back pain and "morphometric" when they are not, and we have generally accepted the assertion that most of the osteoporotic VFs are painless, that is, morphometric. This dichotomous VF definition scheme has been the foundation of osteoporosis epidemiology and the primary endpoint in most pivotal osteoporosis pharmaceutical trials. Although, having served the osteoporosis community well, our clinical experience, refined by recent insights into vertebral anatomy and spinal biomechanics, advances in vertebral imaging, and 2 decades of vertebral augmentation suggest that the spectrum of osteoporotic VFs is more complicated than this scheme suggests. PMID- 26356548 TI - Improvement of Repeated-Sprint Ability and Horizontal-Jumping Performance in Elite Young Basketball Players With Low-Volume Repeated-Maximal-Power Training. AB - PURPOSE: To examine the effects of a low-volume repeated-power-ability (RPA) training program on repeated-sprint and change-of- direction (COD) ability and functional jumping performance. METHODS: Twenty-two male elite young basketball players (age 16.2 +/- 1.2 y, height 190.0 +/- 10.0 cm, body mass 82.9 +/- 10.1 kg) were randomly assigned either to an RPA-training group (n = 11) or a control group (n = 11). RPA training consisted of leg-press exercise, twice a week for 6 wk, of 1 or 2 blocks of 5 sets * 5 repetitions with 20 s of passive recovery between sets and 3 min between blocks with the load that maximized power output. Before and after training, performance was assessed by a repeated-sprint-ability (RSA) test, a repeated-COD-ability test, a hop for distance, and a drop jump followed by tests of a double unilateral hop with the right and left legs. RESULTS: Within-group and between-groups differences showed substantial improvements in slowest (RSAs) and mean time (RSAm) on RSA; best, slowest and mean time on repeated-COD ability; and unilateral right and left hop in the RPA group in comparison with control. While best time on RSA showed no improvement in any group, there was a large relationship (r = .68, 90% CI .43;.84) between the relative decrement in RSAm and RSAs, suggesting better sprint maintenance with RPA training. The relative improvements in best and mean repeated-COD ability were very largely correlated (r = .89, 90% CI .77;.94). CONCLUSIONS: Six weeks of lowvolume (4-14 min/wk) RPA training improved several physical-fitness tests in basketball players. PMID- 26356547 TI - Update on Alcohol and Viral Hepatitis. AB - Alcohol consumption is often associated with viral hepatitis. Although alcohol is known to worsen viral liver disease, the interactions between alcohol and viral hepatitis are not fully understood. Molecular alterations in the liver due to alcohol and viral hepatitis include effects on viral replication, increased oxidative stress, cytotoxicity, and a weakened immune response. Clinically, alcohol enhances disease progression and favors induction of primitive liver neoplasm. The use of new antivirals for hepatitis C and well-established drugs for hepatitis B will determine how viral hepatitis can be controlled in a large percentage of these patients. However, alcohol-related liver disease continues to represent a barrier for access to antivirals, and it remains an unresolved health issue. PMID- 26356549 TI - Measurement of Opening and Closing Angles of Aortic Valve Prostheses In Vivo Using Dual-Source Computed Tomography: Comparison with Those of Manufacturers' in 10 Different Types. AB - OBJECTIVE: The aims of this study were to compare opening and closing angles of normally functioning mechanical aortic valves measured on dual-source computed tomography (CT) with the manufacturers' values and to compare CT-measured opening angles according to valve function. MATERIALS AND METHODS: A total of 140 patients with 10 different types of mechanical aortic valves, who underwent dual source cardiac CT, were included. Opening and closing angles were measured on CT images. Agreement between angles in normally functioning valves and the manufacturer values was assessed using the interclass coefficient and the Bland Altman method. CT-measured opening angles were compared between normal functioning valves and suspected dysfunctioning valves. RESULTS: The CT-measured opening angles of normally functioning valves and manufacturers' values showed excellent agreement for seven valve types (intraclass coefficient [ICC], 0.977; 95% confidence interval [CI], 0.962-0.987). The mean differences in opening angles between the CT measurements and the manufacturers' values were 1.2 degrees in seven types of valves, 11.0 degrees in On-X valves, and 15.5 degrees in ATS valves. The manufacturers' closing angles and those measured by CT showed excellent agreement for all valve types (ICC, 0.953; 95% CI, 0.920-0.972). Among valves with suspected dysfunction, those with limitation of motion (LOM) and an increased pressure gradient (PG) had smaller opening angles than those with LOM only (p < 0.05). CONCLUSION: Dual-source cardiac CT accurately measures opening and closing angles in most types of mechanical aortic valves, compared with the manufacturers' values. Opening angles on CT differ according to the type of valve dysfunction and a decreased opening angle may suggest an elevated PG. PMID- 26356550 TI - A gain-of-function mutation in Msl10 triggers cell death and wound-induced hyperaccumulation of jasmonic acid in Arabidopsis. AB - Jasmonates (JAs) are rapidly induced after wounding and act as key regulators for wound induced signaling pathway. However, what perceives the wound signal and how that triggers JA biosynthesis remains poorly understood. To identify components involved in Arabidopsis wound and JA signaling pathway, we screened for mutants with abnormal expression of a luciferase reporter, which is under the control of a wound-responsive promoter of an ethylene response factor (ERF) transcription factor gene, RAP2.6 (Related to APetala 2.6). The rea1 (RAP2.6 expresser in shoot apex) mutant constitutively expressed the RAP2.6-LUC reporter gene in young leaves. Along with the typical JA phenotypes including shorter petioles, loss of apical dominance, accumulation of anthocyanin pigments and constitutive expression of JA response gene, rea1 plants also displayed cell death and accumulated high levels of JA in response to wounding. The phenotype of rea1 mutant is caused by a gain-of-function mutation in the C-terminus of a mechanosensitive ion channel MscS-like 10 (MSL10). MSL10 is localized in the plasma membrane and is expressed predominantly in root tip, shoot apex and vascular tissues. These results suggest that MSL10 is involved in the wound triggered early signal transduction pathway and possibly in regulating the positive feedback synthesis of JA. PMID- 26356551 TI - The role of PET and PET-CT scanning in assessing response to neoadjuvant therapy in esophageal carcinoma. AB - BACKGROUND: The response to neoadjuvant (radio-)chemotherapy for esophageal carcinoma is often assessed with the aid of positron-emission tomography (PET), either alone or in combination with computed tomography (PET-CT). In this review, we discuss the diagnostic validity and clinical benefit of these imaging techniques. METHODS: We systematically searched the Medline, Embase, and Cochrane Library databases for randomized controlled trials (RCTs) and controlled clinical trials (CCTs) comparing PET-CT with conventional techniques such as endosonography and CT. We then determined the diagnostic validity of these methods on the basis of information from published systematic reviews, updated with further information from more recent primary studies. RESULTS: We did not find any RCTs that addressed the question of the patient-relevant benefit of PET CT. We found 20 studies of diagnostic methods, carried out on a total of 854 patients, of whom 82.2% were male. These studies had a high potential for bias. In two of them, PET-CT was directly compared with endosonography or CT. Estimates of sensitivity and specificity varied widely across studies. 54% of all patients (median value across studies) had no histopathological response to therapy at the end of treatment. Taking a reduction of the standard uptake value (SUV) by at least 35% as a threshold criterion, we found that the median negative predictive value of PET across all studies was 86.5. CONCLUSION: There is no robust evidence for a patient-relevant benefit of PET and PET-CT in patients with esophageal carcinoma. PET could potentially be used to distinguish treatment responders from non-responders after the first cycle of treatment. RCTs with patient-relevant endpoints will be needed in order to determine whether this is useful. PMID- 26356553 TI - The preserve of primary care physicians. PMID- 26356552 TI - The prevalence of celiac disease in children and adolescents in Germany. AB - BACKGROUND: Untreated celiac disease is associated with increased morbidity and mortality. Until now, no up-to-date figures have been available on the prevalence of celiac disease among children and adolescents in Germany, or on the percentage of undiagnosed cases. METHODS: To estimate the prevalence of celiac disease, serum samples obtained from 2003 to 2006 from participants in the German Health Interview and Examination Survey for Children and Adolescents (KiGGS) were studied for celiac disease-specific autoantibodies and total IgA. RESULTS: Of the 12 741 study participants aged 1 to 17 years (6546 boys, 6195 girls), 9 (0.07%) had a reported history of celiac disease. An elevated concentration of serum autoantibodies to tissue transglutaminase was found in 91 children with a normal IgA concentration and in 7 with IgA deficiency. The prevalence of undiagnosed celiac disease, based on positive autoantibody findings, was 0.8% (95% confidence interval 0.6-1.0%), and the overall prevalence of the disease was 0.9%. Seropositive children and adolescents had lower ferritin and red blood cell folate concentrations than seronegative ones; they also tended to be shorter and to weigh less as reflected by age- and sex-standardized z-scores. CONCLUSION: The 0.9% prevalence of celiac disease in Germany, as determined from a combination of serological findings and clinical histories, is similar to reported prevalences elsewhere in Europe and North America. Pediatricians, primary care physicians, internists, and other specialists should be aware of the broad spectrum of clinical manifestations of this disease. Children who have symptoms suggestive of celiac disease or belong to a group at risk for it should be tested for antibodies against tissue transglutaminase, as should symptomatic adults after the exclusion of other possible causes. It is not yet clear whether asymptomatic adults from high-risk groups should be tested. PMID- 26356554 TI - Occupational preventive measures. PMID- 26356555 TI - Diagnosis is difficult. PMID- 26356556 TI - In reply. PMID- 26356557 TI - Validated questionnaire should be used. PMID- 26356558 TI - Lack of physical activity. PMID- 26356559 TI - In reply. PMID- 26356560 TI - The investigation and treatment of female pelvic floor dysfunction. AB - BACKGROUND: 25% of all women report involuntary loss of urine, and 7% may require treatment. METHODS: This review is based on a selection of pertinent literature, including guidelines and Cochrane reviews. RESULTS: The assessment of pelvic floor dysfunction in women begins with a basic evaluation that is followed by special diagnostic tests if indicated. The physician taking the clinical history should inquire about the patient's behavior, personality, social and other stressors, and eating and drinking habits, as well as any mental disorders that may be present, including anxiety disorders, depression, somatization disorders, and disorders of adaptation. Conservative treatment consists mainly of lifestyle changes, physiotherapy, and medication. Stress incontinence is most commonly treated with pelvic floor exercises, with a documented success rate of 56.1% vs. 6% without such treatment (relative risk 8.38, 95% confidence interval 3.67 19.07). If incontinence persists, surgery may be indicated ( implantation of suburethral tension-free slings, or colposuspension). Feedback and biofeedback training can be used to treat an overactive bladder. If these techniques and drug therapy are unsuccessful, botulinum toxin injections can be considered. CONCLUSION: Well-validated treatments for pelvic floor dysfunction are available. Psychosomatic factors must be taken into account and can have a major effect on treatment outcomes. PMID- 26356561 TI - Yoga and Emotion Regulation in High School Students: A Randomized Controlled Trial. AB - Middle adolescents (15-17 years old) are prone to increased risk taking and emotional instability. Emotion dysregulation contributes to a variety of psychosocial difficulties in this population. A discipline such as yoga offered during school may increase emotion regulation, but research in this area is lacking. This study was designed to evaluate the impact of a yoga intervention on the emotion regulation of high school students as compared to physical education (PE). In addition, the potential mediating effects of mindful attention, self compassion, and body awareness on the relationship between yoga and emotion regulation were examined. High school students were randomized to participate in a 16-week yoga intervention (n = 19) or regular PE (n = 18). Pre-post data analyses revealed that emotion regulation increased significantly in the yoga group as compared to the PE group (F (1,32) = 7.50, p = .01, and eta(2) = .19). No significant relationship was discovered between the changes in emotion regulation and the proposed mediating variables. Preliminary results suggest that yoga increases emotion regulation capacities of middle adolescents and provides benefits beyond that of PE alone. PMID- 26356562 TI - RICTOR involvement in the PI3K/AKT pathway regulation in melanocytes and melanoma. AB - Several studies have highlighted the importance of the PI3K pathway in melanocytes and its frequent over-activation in melanoma. However, little is known about regulation of the PI3K pathway in melanocytic cells. We showed that normal human melanocytes are less sensitive to selective PI3K or mTOR inhibitors than to dual PI3K/mTOR inhibitors. The resistance to PI3K inhibitor was due to a rapid AKT reactivation limiting the inhibitor effect on proliferation. Reactivation of AKT was linked to a feedback mechanism involving the mTORC2 complex and in particular its scaffold protein RICTOR. RICTOR overexpression in melanocytes disrupted the negative feedback, activated the AKT pathway and stimulated clonogenicity highlighting the importance of this feedback to restrict melanocyte proliferation. We found that the RICTOR locus is frequently amplified and overexpressed in melanoma and that RICTOR over-expression in NRAS-transformed melanocytes stimulates their clonogenicity, demonstrating that RICTOR amplification can cooperate with NRAS mutation to stimulate melanoma proliferation. These results show that RICTOR plays a central role in PI3K pathway negative feedback in melanocytes and that its deregulation could be involved in melanoma development. PMID- 26356565 TI - Quelling an innate response to dsRNA. PMID- 26356564 TI - Novel Axl-driven signaling pathway and molecular signature characterize high grade ovarian cancer patients with poor clinical outcome. AB - High-grade epithelial ovarian cancer (HGEOC) is a clinically diverse and molecularly heterogeneous disease comprising subtypes with distinct biological features and outcomes. The receptor tyrosine kinases, expressed by EOC cells, and their ligands, present in the microenvironment, activate signaling pathways, which promote EOC cells dissemination. Herein, we established a molecular link between the presence of Gas6 ligand in the ascites of HGEOCs, the expression and activation of its receptor Axl in ovarian cancer cell lines and biopsies, and the progression of these tumors. We demonstrated that Gas6/Axl signalling converges on the integrin beta3 pathway in the presence of the adaptor protein p130Cas, thus inducing tumor cell adhesion to the extracellular matrix and invasion. Accordingly, Axl and p130Cas were significantly co-expressed in HGEOC samples. Clinically, we identified an Axl-associated signature of 62 genes able to portray the HGEOCs with the shortest overall survival. These data biologically characterize a group of HGEOCs and could help guide a more effective therapeutic approach to be taken for these patients. PMID- 26356563 TI - Global phosphotyrosine survey in triple-negative breast cancer reveals activation of multiple tyrosine kinase signaling pathways. AB - Breast cancer is the most prevalent cancer in women worldwide. About 15-20% of all breast cancers are triple negative breast cancer (TNBC) and are often highly aggressive when compared to other subtypes of breast cancers. To better characterize the biology that underlies the TNBC phenotype, we profiled the phosphotyrosine proteome of a panel of twenty-six TNBC cell lines using quantitative high resolution Fourier transform mass spectrometry. A heterogeneous pattern of tyrosine kinase activation was observed based on 1,789 tyrosine phosphorylated peptides identified from 969 proteins. One of the tyrosine kinases, AXL, was found to be activated in a majority of aggressive TNBC cell lines and was accompanied by a higher level of AXL expression. High levels of AXL expression are correlated with a significant decrease in patient survival. Treatment of cells bearing activated AXL with a humanized AXL antibody inhibited cell proliferation and migration in vitro, and tumor growth in mice. Overall, our global phosphoproteomic analysis provided new insights into the heterogeneity in the activation status of tyrosine kinase pathways in TNBCs. Our approach presents an effective means of identifying important novel biomarkers and targets for therapy such as AXL in TNBC. PMID- 26356566 TI - The cerebral cavernous malformations proteins. PMID- 26356567 TI - New tricks for KDEL receptors. PMID- 26356568 TI - Priming persistence of HCV. PMID- 26356569 TI - VDR and gemini ligands. PMID- 26356570 TI - Deconvoluting AMPK dynamics. PMID- 26356571 TI - Tension across adherens junctions: when less is more. PMID- 26356572 TI - Protective CD8+ T cell memory without help. PMID- 26356573 TI - PTX3 orchestrates tissue repair. PMID- 26356574 TI - Scattering particles increase absorbance of dyes--a model study with relevance for sunscreens. AB - Sunscreens used for the protection of human skin against the harmful effects of solar radiation contain UV absorbers as key ingredients, which are either dissolved in one of the phases of the preparation or, when insoluble, suspended as particles. Although the UV protective effect of particulate UV filters, inorganic and organic, is mainly due to absorption, they scatter UV and visible light. The scattering can have an additional attenuating effect on the incoming radiation by increasing the pathlength of the photons, especially when soluble filters are also present. This is investigated with model systems of dyes and absorbing and non-absorbing particles. The presence of particles causes an increase of the dye absorbance without changing dye concentration or cuvette thickness. It is possible to relate this amplification of dye absorbance to the turbidity of the system. Plots are constructed which allow for a given particle type the representation of all data on one single curve, though measured at different turbidity and cuvette thickness. With that, extrapolations to practical applications of sunscreens are possible. PMID- 26356575 TI - Kinetic and Mechanistic Assessment of Alkanol/Alkanal Decarbonylation and Deoxygenation Pathways on Metal Catalysts. AB - This study combines theory and experiment to determine the kinetically relevant steps and site requirements for deoxygenation of alkanols and alkanals. These reactants deoxygenate predominantly via decarbonylation (C-C cleavage) instead of C-O hydrogenolysis on Ir, Pt, and Ru, leading to strong inhibition effects by chemisorbed CO (CO*). C-C cleavage occurs via unsaturated species formed in sequential quasi-equilibrated dehydrogenation steps, which replace C-H with C metal bonds, resulting in strong inhibition by H2, also observed in alkane hydrogenolysis. C-C cleavage occurs in oxygenates only at locations vicinal to the C?O group in RCCO* intermediates, because such adjacency weakens C-C bonds, which also leads to much lower activation enthalpies for oxygenates than hydrocarbons. C-O hydrogenolysis rates are independent of H2 pressure and limited by H*-assisted C-O cleavage in RCHOH* intermediates on surfaces with significant coverages of CO* formed in decarbonylation events. The ratio of C-O hydrogenolysis to decarbonylation rates increased almost 100-fold as the Ir cluster size increased from 0.7 to 7 nm; these trends reflect C-O hydrogenolysis reactions favored on terrace sites, while C-C hydrogenolysis prefers sites with lower coordination, because of the relative size of their transition states and the crowded nature of CO*-covered surfaces. C-O hydrogenolysis becomes the preferred deoxygenation route on Cu-based catalysts, thus avoiding CO inhibition effects. The relative rates of C-O and C-C cleavage on these metals depend on their relative ability to bind C atoms, because C-C cleavage transitions states require an additional M-C attachment. PMID- 26356576 TI - Effects of Steroid Hormones on Sex Differences in Cerebral Perfusion. AB - Sex differences in the brain appear to play an important role in the prevalence and progression of various neuropsychiatric disorders, but to date little is known about the cerebral mechanisms underlying these differences. One widely reported finding is that women demonstrate higher cerebral perfusion than men, but the underlying cause of this difference in perfusion is not known. This study investigated the putative role of steroid hormones such as oestradiol, testosterone, and dehydroepiandrosterone sulphate (DHEAS) as underlying factors influencing cerebral perfusion. We acquired arterial spin labelling perfusion images of 36 healthy adult subjects (16 men, 20 women). Analyses on average whole brain perfusion levels included a multiple regression analysis to test for the relative impact of each hormone on the global perfusion. Additionally, voxel based analyses were performed to investigate the sex difference in regional perfusion as well as the correlations between local perfusion and serum oestradiol, testosterone, and DHEAS concentrations. Our results replicated the known sex difference in perfusion, with women showing significantly higher global and regional perfusion. For the global perfusion, DHEAS was the only significant predictor amongst the steroid hormones, showing a strong negative correlation with cerebral perfusion. The voxel-based analyses revealed modest sex-dependent correlations between local perfusion and testosterone, in addition to a strong modulatory effect of DHEAS in cortical, subcortical, and cerebellar regions. We conclude that DHEAS in particular may play an important role as an underlying factor driving the difference in cerebral perfusion between men and women. PMID- 26356578 TI - Meeting Report: Plant Science Student Conference (PSSC) 2015--Young researchers in green biotechnology. PMID- 26356577 TI - Sleep Related Breathing Disorders and Inflammation - The Missing Link? A Cohort Study Evaluating the Interaction of Inflammation and Sleep Related Breathing Disorders and Effects of Treatment. AB - INTRODUCTION: Sleep related breathing disorders (SRBD) are associated with both obesity and systemic inflammation. While the relationship between obesity and SRBD is established, the causality between inflammation and SRBD remains unclear. In this study we investigated the relation between SRBD and C-reactive protein (CRP) as a parameter of inflammation and the influence of SRBD treatment on CRP with additional regard to changes in metabolic and cardiovascular parameters. METHODS: Polysomnography (PSG) and laboratory data of patients diagnosed with SRBD over a period of 5 years were prospectively collected in a database and retrospectively analysed regarding the association of SRBD (according to apnoea hypopnoea- index (AHI), duration of events and extent of desaturation) to CRP, blood pressure, cholesterol, fasting plasma glucose, HbA1c, quality of life measured via a visual analogue scale (VAS 0-100%), and the effects of SRBD therapy on these parameters. RESULTS: 716 patients were included in the study, 171 with mild SRBD (AHI >=5 to <15/h), 209 with moderate SRBD (AHI 15 to <30/h), 336 with severe SRBD (AHI >=30/h). Results according to severity of SRBD. Severe SRBD was significantly associated with elevated levels of CRP (3.7 [1.8-7.0] mg/l, vs. moderate (p = 0.001), and mild SRBD (p<0.001), and higher prevalence of hypertension as compared to moderate and mild SRBD (p<0.001, respectively). Results in highly successful treatment. If SRBD treatment was highly successful (AHI <5/h), CRP and quality of life improved significantly (p = 0.001 and p = 0.002), as did blood pressure (p<0.001 for systolic and diastolic values), although BMI increased (p<0.001). Results in partially successful treatment. If success was defined as reduction of AHI of >=50%, CRP also decreased (p<0.001), as did blood pressure (p<0.001). Again, BMI increased (p<0.001). CONCLUSION: This is the first study to show an association of SRBD and CRP independently of BMI in a large cohort. The SRBD therapy-induced CRP decrease was not associated with BMI changes or metabolic changes but rather with the magnitude of AHI improvement. PMID- 26356579 TI - Population genetic structure and colonization history of short ninespine sticklebacks (Pungitius kaibarae). AB - The contemporary distribution and genetic structure of a freshwater fish provide insight into its historical geodispersal and geographical isolation following Quaternary climate changes. The short ninespine stickleback, Pungitius kaibarae, is a small gasterosteid fish occurring in freshwater systems on the Korean Peninsula and in southeast Russia. On the Korean Peninsula, P. kaibarae populations are distributed in three geographically separated regions: the NE (northeast coast), SE (southeast coast), and a limited area in the ND (Nakdong River). In this study, we used mitochondrial loci and microsatellites to investigate the evolutionary history of P. kaibarae populations by assessing their pattern of genetic structure. Our analyses revealed a marked level of divergence among three regional populations, suggesting a long history of isolation following colonization, although ND individuals showed relatively higher genetic affinity to populations from SE than those from NE. The populations from NE showed a great degree of interpopulation differentiation, whereas populations from SE exhibited only weak genetic structuring. Upon robust phylogenetic analysis, P. kaibarae formed a monophyletic group with Russian P. sinensis and P. tymensis with strong node confidence values, indicating that P. kaibarae populations on the Korean Peninsula originated from the southward migration of its ancestral lineage around the middle Pleistocene. PMID- 26356580 TI - Agreement between 2D and 3D radiographic outcome assessment one year after periapical surgery. AB - AIM: To compare 2D with 3D radiography in assessing the treatment outcome 1 year after periapical surgery. METHODOLOGY: In this prospective study, periapical radiographs (PA) and cone beam computed tomography (CBCT) were performed 1 year after periapical surgery. Three calibrated observers independently evaluated the radiographs for the presence and type of periapical radiolucencies. Ratings in PA were compared to those in bucco-lingual and mesio-distal CBCT images (coronal and sagittal planes), and the ratings of the latter two were also compared between each other. Further, maximum size diameters of radiolucencies were measured on CBCT scans, and the calculated means were correlated with the types of radiolucency. Statistical analysis was completed using Friedman rank sum tests, the Wilcoxon signed rank test and the Pearson correlation coefficient. RESULTS: A total of 61 roots in 54 patients were eligible for the final assessment. On average, the intra-observer ratings were identical in 59.6% when comparing PA and CBCT (kappa 0.112 to 0.192). A very high intra-observer agreement (93.4%) was noted when comparing bucco-lingual and mesio-distal CBCT ratings (kappa 0.797 to 1). Interobserver agreement was higher for PA (68.8%) than for CBCT (bucco lingual 45.9%, mesio-distal 47.5%), but without reaching significant differences. The calculated mean size of persistent radiolucencies in CBCT scans correlated well with the assigned types of radiolucency. CONCLUSION: CBCT images showed in nearly a third of the evaluated cases a worse situation than PA. There is a need to define criteria to assess the 'radiographic healing' in CBCT following periapical surgery. PMID- 26356581 TI - Alkaloids in Erythrina by UPLC-ESI-MS and In Vivo Hypotensive Potential of Extractive Preparations. AB - Erythrina species are used in popular medicine as sedative, anxiolytic, anti inflammatory, and antihypertensive. In this work, we investigated the chemical composition of extracts obtained from leaves of E. falcata and E. crista-galli. The hypotensive potential of E. falcata and the mechanism of action were also studied. The extracts were obtained by maceration and infusion. The total content of phenolic compounds and flavonoids was estimated by spectrophotometric methods. The chemical constituents were studied performing a chromatographic analysis by UPLC-ESI-MS. For in vivo protocols, blood pressure and heart rate were measured by the invasive hemodynamic monitoring method. Different concentrations of extracts and drugs such as L-NAME, losartan, hexamethonium, and propranolol were administrated i.v. The results of total phenolic contents for E. falcata and E. crista-galli were 1.3193-1.4989 mgGAE/mL for maceration and 0.8771-0.9506 mgGAE/mL for infusion. In total flavonoids, the content was 7.7829-8.1976 mg RE/g for maceration and 9.3471-10.4765 RE mg/g for infusion. The chemical composition was based on alkaloids, suggesting the presence of erythristemine, 11beta methoxyglucoerysodine, erysothiopine, 11beta-hydroxyerysodine-glucose, and 11 hydroxyerysotinone-rhamnoside. A potent dose-dependent hypotensive effect was observed for E. falcata, which may be related to the route of beta-adrenergic receptors. PMID- 26356582 TI - Enantioselective Steglich Rearrangement of Oxindole Derivatives by Easily Accessible Chiral N,N-4-(Dimethylamino)pyridine Derivatives. AB - Chiral N,N-4-(dimethylamino)pyridine (DMAP) derivatives, which can be readily prepared by the Ugi multicomponent reaction in a one-pot manner, have been efficiently applied to the enantioselective Steglich rearrangement of oxindole derivatives to give the desired products bearing a quaternary carbon center in high yield (>98% yield) and with high enantioselectivity (up to 99:1 er). PMID- 26356583 TI - Processing of false belief passages during natural story comprehension: An fMRI study. AB - The neural correlates of theory of mind (ToM) are typically studied using paradigms which require participants to draw explicit, task-related inferences (e.g., in the false belief task). In a natural setup, such as listening to stories, false belief mentalizing occurs incidentally as part of narrative processing. In our experiment, participants listened to auditorily presented stories with false belief passages (implicit false belief processing) and immediately after each story answered comprehension questions (explicit false belief processing), while neural responses were measured with functional magnetic resonance imaging (fMRI). All stories included (among other situations) one false belief condition and one closely matched control condition. For the implicit ToM processing, we modeled the hemodynamic response during the false belief passages in the story and compared it to the hemodynamic response during the closely matched control passages. For implicit mentalizing, we found activation in typical ToM processing regions, that is the angular gyrus (AG), superior medial frontal gyrus (SmFG), precuneus (PCUN), middle temporal gyrus (MTG) as well as in the inferior frontal gyrus (IFG) billaterally. For explicit ToM, we only found AG activation. The conjunction analysis highlighted the left AG and MTG as well as the bilateral IFG as overlapping ToM processing regions for both implicit and explicit modes. Implicit ToM processing during listening to false belief passages, recruits the left SmFG and billateral PCUN in addition to the "mentalizing network" known form explicit processing tasks. PMID- 26356584 TI - [Obstructive colitis following the ingestion of laxatives during bowel preparation for colonoscopy: a report of two cases]. AB - The first case of obstructive colitis (OC) was observed in a 71-year-old man who presented to our hospital complaining of frank blood in the stool. After receiving a laxative for bowel preparation, he complained of lower abdominal pain. Colonoscopy revealed a circumferential tumor at the rectosigmoid junction. Diffuse erythema with erosion and ulceration was observed 5cm proximal to the tumor. The second case of OC was observed in a 73-year-old man. He was admitted to our hospital for endoscopic resection of a colonic polyp. After receiving a laxative for bowel preparation, he complained of lower abdominal pain. Colonoscopy revealed that the rectum was filled with feces. Diffuse erythema with ulceration was observed in the part beyond the feces. In both cases, although the cause of the obstruction differed, the obstructing lesions were located at the rectum, and the OC appeared to be induced by laxative ingestion. PMID- 26356585 TI - Understanding a Value Chain in Health Care. AB - As the US health care system transitions toward a value-based system, providers and health care organizations will have to closely scrutinize their current processes of care. To do this, a value chain analysis can be performed to ensure that only the most efficient steps are followed in patient care. Ultimately this will produce a higher quality or equal quality product for less cost by eliminating wasteful steps along the way. PMID- 26356586 TI - Priority role of epinephrine in anaphylaxis further underscored--the impact on biphasic anaphylaxis. PMID- 26356587 TI - A new approach to epinephrine deficiency and fatal food anaphylaxis. PMID- 26356588 TI - Role of mast cells in trauma and neuroinflammation in allergy immunology. PMID- 26356589 TI - Allergen of the Month--Western Red Cedar. PMID- 26356591 TI - Glaucoma Surgery and Anticoagulant Therapy. PMID- 26356590 TI - Association of CD44 Gene Polymorphism with Survival of NSCLC and Risk of Bone Metastasis. AB - BACKGROUND: Previous studies have reported CD44 expression played an important role in the development and progression of tumor. The aim of study was to investigate whether single nucleotide polymorphisms (SNPs) of CD44 gene were associated with risk of non-small cell lung cancer (NSCLC), survival and occurrence rate of bone metastasis in patients with NSCLC. MATERIAL AND METHODS: A total of 234 patients with NSCLC between 2003 and 2010 were enrolled in this study and 468 healthy persons were used as controls. Two polymorphisms, rs13347 and rs187115, in the CD44 gene were genotyped using DNA from blood lymphocytes. For statistical analysis we used the chi-square test, Fisher's exact test, Kaplan Meier method, and log-rank test. RESULTS: CD44 gene rs13347 polymorphism was not associated with NSCLC risk. For rs187115, the association with NSCLC risk was observed (P<0.001). Allele G carriers had significantly higher occurrence rates of bone metastasis (OR=0.4, 95%CI: 0.20-0.64, P<0.001) and more advanced tumor stage (OR=2.6, 95%CI: 1.50-4.45, P=0.001) compared to carriers of allele A. The survival rates for patients with AA genotype were significantly higher than for patients with the AG+GG genotypes (P<0.001). In multivariate analysis of survival in NSCLC patients, significant predictors were CD44 gene (AG+GG) (RR=0.48, 95%CI: 0.34-0.68, P<0.001), tumor stage (RR=0.45, 95%CI: 0. 0.31-0.65, P<0.001), and bone metastasis (RR=1.52, 95%CI: 1.05-2.21, P=0.027). CONCLUSIONS: CD44 gene rs187115 polymorphism is a potential predictive marker of survival in NSCLC patients, and is significantly correlated with bone metastasis and tumor stage. PMID- 26356592 TI - Interfacial Tension Effect on Cell Partition in Aqueous Two-Phase Systems. AB - Aqueous two-phase systems (ATPS) provide a mild environment for the partition and separation of cells. We report a combined experimental and theoretical study on the effect of interfacial tension of polymeric ATPS on the partitioning of cells between two phases and their interface. Two-phase systems are generated using polyethylene glycol and dextran of specific properties as phase-forming polymers and culture media as the solvent component. Ultralow interfacial tensions of the solutions are precisely measured using an axisymmetric drop shape analysis method. Partition experiments show that two-phase systems with an interfacial tension of 30 MUJ/m(2) result in distribution of majority of cells to the bottom dextran phase. An increase in the interfacial tension results in a distribution of cells toward the interface. An independent cancer cell spheroid formation assay confirms these observations: a drop of the dextran phase containing cancer cells is dispensed into the immersion polyethylene glycol phase to form a cell containing drop. Only at very small interfacial tensions do cells remain within the drop to aggregate into a spheroid. We perform a thermodynamic modeling of cell partition to determine variations of free energy associated with displacement of cells in ATPS with respect to the ultralow interfacial tensions. This modeling corroborates with the experimental results and demonstrates that at the smallest interfacial tension of 30 MUJ/m(2), the free energy is a minimum with cells in the bottom phase. Increasing the interfacial tension shifts the minimum energy and partition of cells toward the interfacial region of the two aqueous phases. Examining differences in the partition behavior and minimum free energy modeling of A431.H9 cancer cells and mouse embryonic stem cells shows that the surface properties of cells further modulate partition in ATPS. This combined approach provides a fundamental understanding of interfacial tension role on cell partition in ATPS and a framework for future studies. PMID- 26356594 TI - Molecular Endotyping of Pulmonary Fibrosis. AB - Idiopathic pulmonary fibrosis (IPF) is a devastating and incurable progressive fibrotic lung condition associated with a significant disease burden. In recent years there has been an exponential increase in the number of preclinical and clinical studies performed in IPF. IPF is defined according to rigid diagnostic criteria; hence, a significant subset of patients with unclassifiable disease has been excluded from these studies. The traditional diagnostic classification of all progressive fibrotic lung diseases uses specific clinical, radiological, and histopathological features to define each condition. However, the considerable heterogeneity within each form of pulmonary fibrosis has raised the possibility of distinct pathophysiological mechanisms culminating in a common phenotype. Thus, the classification of fibrotic lung diseases according to the driving molecular mechanisms rather than specific user-defined histopathological and radiological features could improve several aspects of clinical care. Discoveries from basic science research have defined multiple complex molecular pathways involved in the pathogenesis of pulmonary fibrosis that may provide markers for the molecular endotyping of this disease. In addition, these molecular pathways have revealed potential therapeutic targets. Reclassifying progressive fibrotic lung diseases according to molecular endotypes may allow for more accurate assessment of prognosis and individualized treatment. Furthermore, recent developments that have been applied to a narrow group of patients with IPF may be applicable to those with other progressive fibrotic lung diseases. This review presents the latest developments from translational research in this area and explains how molecular endotyping could revolutionize the diagnosis, stratification, and treatment of pulmonary fibrosis. PMID- 26356595 TI - Mortality outcomes in patients receiving direct oral anticoagulants: a systematic review and meta-analysis of randomized controlled trials. AB - BACKGROUND: Direct oral anticoagulants (DOACs) are widely used as an alternative for warfarin. However, the impact of DOACs on mortality outcomes compared with warfarin remains unclear. OBJECTIVE: To estimate the mortality outcomes in patients treated with DOACs vs. warfarin (or another vitamin K antagonist). METHODS: MEDLINE, EMBASE and CENTRAL databases (inception to September 2014), conference abstracts and www.clinicaltrials.gov, were searched, without language restriction. Studies were selected if there were phase III, randomized trials comparing DOACs with warfarin in patients with non-valvular atrial fibrillation or venous thromboembolism. RESULTS: Thirteen randomized controlled trials involving 102 707 adult patients were included in the analysis. The case-fatality rate of major bleeding was 7.57% (95% CI, 6.53-8.68; I(2) = 0%) in patients taking DOACs and 11.04% (95% CI, 9.16-13.07; I(2) = 33.3%) in patients taking warfarin. The rate of fatal bleeding in adult patients receiving DOACs was 0.16 per 100 patient-years (95% CI, 0.12-0.20; I(2) = 36.5%). When compared with warfarin, DOACs were associated with significant reductions in fatal bleeding (RR, 0.53; 95% CI, 0.43-0.64; I(2) = 0%), cardiovascular mortality (RR, 0.88; 95% CI, 0.82-0.94; I(2) = 0%) and all-cause mortality (RR, 0.91; 95% CI, 0.87-0.96; I(2) = 0%). CONCLUSIONS: The use of DOACs compared with warfarin is associated with a lower rate of fatal bleeding, case-fatality rate of major bleeding, cardiovascular mortality and all-cause mortality. PMID- 26356596 TI - Optimization of Experimental Parameters to Explore Small-Ligand/Aptamer Interactions through Use of (1) H NMR Spectroscopy and Molecular Modeling. AB - Aptamers constitute an emerging class of molecules designed and selected to recognize any given target that ranges from small compounds to large biomolecules, and even cells. However, the underlying physicochemical principles that govern the ligand-binding process still have to be clarified. A major issue when dealing with short oligonucleotides is their intrinsic flexibility that renders their active conformation highly sensitive to experimental conditions. To overcome this problem and determine the best experimental parameters, an approach based on the design-of-experiments methodology has been developed. Here, the focus is on DNA aptamers that possess high specificity and affinity for small molecules, L-tyrosinamide, and adenosine monophosphate. Factors such as buffer, pH value, ionic strength, Mg(2+) -ion concentration, and ligand/aptamer ratio have been considered to find the optimal experimental conditions. It was then possible to gain new insight into the conformational features of the two ligands by using ligand-observed NMR spectroscopic techniques and molecular mechanics. PMID- 26356597 TI - Towards biological plausibility of electronic noses: A spiking neural network based approach for tea odour classification. AB - The paper presents a novel encoding scheme for neuronal code generation for odour recognition using an electronic nose (EN). This scheme is based on channel encoding using multiple Gaussian receptive fields superimposed over the temporal EN responses. The encoded data is further applied to a spiking neural network (SNN) for pattern classification. Two forms of SNN, a back-propagation based SpikeProp and a dynamic evolving SNN are used to learn the encoded responses. The effects of information encoding on the performance of SNNs have been investigated. Statistical tests have been performed to determine the contribution of the SNN and the encoding scheme to overall odour discrimination. The approach has been implemented in odour classification of orthodox black tea (Kangra Himachal Pradesh Region) thereby demonstrating a biomimetic approach for EN data analysis. PMID- 26356598 TI - Reinforcement learning solution for HJB equation arising in constrained optimal control problem. AB - The constrained optimal control problem depends on the solution of the complicated Hamilton-Jacobi-Bellman equation (HJBE). In this paper, a data-based off-policy reinforcement learning (RL) method is proposed, which learns the solution of the HJBE and the optimal control policy from real system data. One important feature of the off-policy RL is that its policy evaluation can be realized with data generated by other behavior policies, not necessarily the target policy, which solves the insufficient exploration problem. The convergence of the off-policy RL is proved by demonstrating its equivalence to the successive approximation approach. Its implementation procedure is based on the actor-critic neural networks structure, where the function approximation is conducted with linearly independent basis functions. Subsequently, the convergence of the implementation procedure with function approximation is also proved. Finally, its effectiveness is verified through computer simulations. PMID- 26356599 TI - Neural networks with non-uniform embedding and explicit validation phase to assess Granger causality. AB - A challenging problem when studying a dynamical system is to find the interdependencies among its individual components. Several algorithms have been proposed to detect directed dynamical influences between time series. Two of the most used approaches are a model-free one (transfer entropy) and a model-based one (Granger causality). Several pitfalls are related to the presence or absence of assumptions in modeling the relevant features of the data. We tried to overcome those pitfalls using a neural network approach in which a model is built without any a priori assumptions. In this sense this method can be seen as a bridge between model-free and model-based approaches. The experiments performed will show that the method presented in this work can detect the correct dynamical information flows occurring in a system of time series. Additionally we adopt a non-uniform embedding framework according to which only the past states that actually help the prediction are entered into the model, improving the prediction and avoiding the risk of overfitting. This method also leads to a further improvement with respect to traditional Granger causality approaches when redundant variables (i.e. variables sharing the same information about the future of the system) are involved. Neural networks are also able to recognize dynamics in data sets completely different from the ones used during the training phase. PMID- 26356600 TI - Transient cold agglutinins associated with Mycoplasma cynos pneumonia in a dog. AB - This report details a case of reversible cold agglutinins in a dog with Mycoplasma cynos pneumonia. An 11-month-old female spayed Rhodesian Ridgeback was presented for lethargy and cough. Thoracic radiographs revealed an alveolar pattern present bilaterally in the cranioventral lung lobes. Septic neutrophilic inflammation with suspected Mycoplasma sp. organisms was noted on cytologic examination of a trans-tracheal wash, and the dog was treated empirically with IV ampicillin/sulbactam and enrofloxacin pending culture results. Red blood cell agglutination was noted unexpectedly on several blood film reviews during hospitalization; however, the dog never developed clinical or laboratory evidence of hemolysis. Cold agglutinins were demonstrated based on the results of a saline dilution and cold agglutinin test that showed agglutination at 4 degrees C but not at room temperature (21 degrees C) or 37 degrees C. Based on a positive culture for M cynos, the dog was treated for 8 weeks with oral enrofloxacin. After clinical and radiographic resolution of the pneumonia, repeated saline dilution and cold agglutinin tests of peripheral blood were negative at all temperatures. Reversible, asymptomatic cold agglutinins are common in human patients with mycoplasma pneumonia, but this is the first reported case in a dog. PMID- 26356601 TI - A Novel Method for Endoscopic Closure of Bladder Perforations During NOTES: Initial Experience from Animal Studies. AB - OBJECTIVES: Translumenal access site closure remains a major challenge in natural orifice translumenal endoscopic surgery (NOTES((r)); American Society for Gastrointestinal Endoscopy [Oak Brook, IL] and Society of American Gastrointestinal and Endoscopic Surgeons [Los Angeles, CA]). We assessed the feasibility and safety of using reserved threads to close the bladder perforation during NOTES and analyzed this novel technique in a live porcine model. MATERIALS AND METHODS: Five female pigs were used in this study. With the animal under general anesthesia, a self-made trocar was inserted into the bladder. Under ureteroscopic guidance, the anterior bladder wall was punctured by a needle into the abdominal wall, and two reserved lines were placed. The bladder perforation was closed with the reserved lines. Procedure time and effectiveness of the closure were recorded and evaluated. RESULTS: We completed a total of 5 cases of animal experiments. The first case failed because the weight and size of the animal were too large. The remaining 4 cases were successful. The procedure times were 45, 30, 25, and 25 minutes, respectively. The perforations were closed completely. CONCLUSIONS: The novel method of using reserved thread to close the bladder perforation was safe and effective. Further large-scale survival studies are needed to prove its clinical potential. PMID- 26356602 TI - A single-center United States experience with bleeding Dieulafoy lesions of the small bowel: diagnosis and treatment with single-balloon enteroscopy. AB - INTRODUCTION: A Dieulafoy lesion (DL) of the small bowel can cause severe gastrointestinal bleeding, and presents a difficult clinical setting for endoscopists. Limited data exists on the therapeutic yield of treating DLs of the small bowel using single-balloon enteroscopy (SBE). METHODS: Data were collected from Tampa General Hospital a 1 018-bed teaching hospital affiliated with University of South Florida in Tampa, Florida. Patients were selected from a database of patients that underwent SBE from January 2010 - August 2013. RESULTS: Eight patients were found to have DL an incidence of 2.6 % of 309 SBE performed for obscure gastrointestinal bleeding. 7/8 were identified in the jejunum, with one found in the duodenum. The mean age of patients with DL was 71.5 years old. 6/8 patients were on some form of anticoagulant/antiplatelet agent. The primary modality of therapy employed was electrocautery, multipolar electrocoagulation in seven patients and APC (argon plasma coagulation) in one patient. In three patients, electrocoagulation was unsuccessful and hemostasis was achieved with clip placement. Three patients required repeat SBE with one found to have rebleeding from a failed clip with hemostasis achieved upon reapplication of one clip. CONCLUSION: In our United States' experience, SBE offers a reasonable therapeutic approach to treat DL of the small bowel with low rates of rebleeding, no adverse events, and no patient requiring surgery. PMID- 26356603 TI - Genome-wide association links candidate genes to resistance to Plum Pox Virus in apricot (Prunus armeniaca). AB - In fruit tree species, many important traits have been characterized genetically by using single-family descent mapping in progenies segregating for the traits. However, most mapped loci have not been sufficiently resolved to the individual genes due to insufficient progeny sizes for high resolution mapping and the previous lack of whole-genome sequence resources of the study species. To address this problem for Plum Pox Virus (PPV) candidate resistance gene identification in Prunus species, we implemented a genome-wide association (GWA) approach in apricot. This study exploited the broad genetic diversity of the apricot (Prunus armeniaca) germplasm containing resistance to PPV, next-generation sequence-based genotyping, and the high-quality peach (Prunus persica) genome reference sequence for single nucleotide polymorphism (SNP) identification. The results of this GWA study validated previously reported PPV resistance quantitative trait loci (QTL) intervals, highlighted other potential resistance loci, and resolved each to a limited set of candidate genes for further study. This work substantiates the association genetics approach for resolution of QTL to candidate genes in apricot and suggests that this approach could simplify identification of other candidate genes for other marked trait intervals in this germplasm. PMID- 26356604 TI - Mental Health Services and Public Safety: Substance Abuse Outpatient Visits Were Associated with Reduced Crime Rates in a Swedish Cohort. AB - Substance abuse is related to offending and substance abuse treatment has been associated with reductions in criminal behavior. This cohort study aimed to explore the relationship between participation in substance abuse interventions and general criminal recidivism among offenders with a combination of mental health problems and substance use problems. In total, 150 Swedish offenders with self-reported mental health and substance use problems were followed for approximately three years with regard to participation in substance abuse interventions and criminal recidivism. Participants with at least three planned visits to specialized outpatient substance abuse clinics had a substantially reduced risk of reoffending as compared to those with fewer than three such visits (HR = 0.47, 95% CI 0.29-0.77). For those with at least three planned visits, general criminal recidivism was reduced by 75% during periods of participation in outpatient visits, as compared to periods of non-participation (HR = 0.25, 95% CI 0.11-0.60). For offenders with mental health problems and substance use problems, outpatient substance abuse interventions could be regarded as important from a clinical risk management perspective, and be encouraged. PMID- 26356606 TI - Smoking, Methylation at AHRR, and Recidivism Risk in a Community Correction Sample of Individuals at High Risk for Recidivism. AB - Individuals supervised by community correction programs have a high rate of tobacco use and high frequency of tobacco dependence. As compared with supervisees without tobacco dependence, probationers and parolees with tobacco dependence were more likely to abuse other substances and report poorer health. In this sample of 374 predominantly felon and repeat offenders, at high risk for recidivism, over 95% of subjects smoked or used other tobacco products, 87% were actively smoking at the time of interview, and 70% met criteria for lifetime tobacco dependence. Seventy-four percent had DNA demethylation, defined as methylation less than 83%, at the aryl hydrocarbon receptor repressor (AHRR) residue interrogated by cg0557592 at the time of interview. Seventy-eight percent exhibited four-year recidivism. Demethylation was associated with four-year recidivism in women, but not men. These findings suggest that methylation at cg05575921 serves as a semi-quantitative measure of both recent use and lifetime burden, that community correction populations continue to smoke at high risk, that measurement of methylation may add to the identification of female offenders at risk for recidivism, and that treatments to assist in cessation efforts are desperately needed. PMID- 26356605 TI - Increased COUP-TFII expression in adult hearts induces mitochondrial dysfunction resulting in heart failure. AB - Mitochondrial dysfunction and metabolic remodelling are pivotal in the development of cardiomyopathy. Here, we show that myocardial COUP-TFII overexpression causes heart failure in mice, suggesting a causal effect of elevated COUP-TFII levels on development of dilated cardiomyopathy. COUP-TFII represses genes critical for mitochondrial electron transport chain enzyme activity, oxidative stress detoxification and mitochondrial dynamics, resulting in increased levels of reactive oxygen species and lower rates of oxygen consumption in mitochondria. COUP-TFII also suppresses the metabolic regulator PGC-1 network and decreases the expression of key glucose and lipid utilization genes, leading to a reduction in both glucose and oleate oxidation in the hearts. These data suggest that COUP-TFII affects mitochondrial function, impairs metabolic remodelling and has a key role in dilated cardiomyopathy. Last, COUP TFII haploinsufficiency attenuates the progression of cardiac dilation and improves survival in a calcineurin transgenic mouse model, indicating that COUP TFII may serve as a therapeutic target for the treatment of dilated cardiomyopathy. PMID- 26356607 TI - Sclerosing Sromal Tumor of the Ovary in Postmenopausal Women: A Report of Two Cases. AB - Sclerosing stromal tumor (SST) was first delineated as a distinct ovarian sex cord stromal tumor in 1973 by Chalvardjian and Scully. It is a benign neoplasm, distinguished from other ovarian stromal tumors by the production of collagen and a pseudolobular pattern, and it tends to occur in the second and third decades of life in diagnosed patients. We discovered two rare cases of SST in post menopausal women which are the topic of this report. These case studies are accompanied by a brief review of the literature. PMID- 26356608 TI - [Schizophrenia or a group of endogenous diseases? The past and the present]. AB - A critical analysis of the main concepts of schizophrenia (from the Kraepelin paradigm to the current studies attempted to "destruct" schizophrenia as nosologically independent disease) is presented. In author's opinion, the elimination of schizophrenia may lead to negative consequences as in aspect of clinical practice (the diagnosis of schizophrenia provides information about disease course, clinical and social outcomes) as well as in aspect of denial of autochthonous (endogenous) origin of mental disorders that fall under this definition. Based on the current level of knowledge, manifestation of these disorders can't be well explained by the adverse effects of situational, psychogenic or somatogenic factors. The restriction of the definition of schizophrenia ("process" schizophrenia) should be brought about by the elimination of a group of schizophrenia spectrum disorders (schizotypal disorder, schizoaffective disorder, delusional psychosis). PMID- 26356609 TI - [Gluten migraine]. AB - OBJECTIVE: to study the prevalence of migraine among patients with celiac disease (CD) and clinical features of "gluten migraine" syndrome and to assess the efficacy of gluten diet in its treatment. MATERIAL AND METHODS: Authors examined 200 CD patients (main group) and 100 patients with reflux esophagitis and without CD (control group). All patients fulfilled the headache diary during three months before the diagnosis of migraine was made and six months during gluten diet. RESULTS AND CONCLUSION: CD group had migraine syndrome four times more often than the control group (48.5%; p<0.001). In CD group migraine attacks were 2.5 times more frequent than in the control group (r=0.004), but the duration of the attacks was less long, 8 hours in average. The migraine attacks measured by the Visual Analog Scale were less intensive, 55% in average, and had a later onset. The attacks were more frequent in CD patients who were older than 50 years old (r<0.05). The attacks disappeared in 25% of patients with migraine syndrome who were on the gluten diet and the reduction in the intensity and/or frequency of attacks was observed in 38% of patients. We revealed the clear association between migraine syndrome and CD and the high efficacy of gluten diet in the treatment of migraine symptoms. PMID- 26356610 TI - [The clinical picture of nonsyndromic craniosynostosis in children]. AB - OBJECTIVE: to study clinical presentations of nonsyndromic craniosynostosis (NCS) in children. MATERIAL AND METHODS: Authors analyzed 56 cases of different forms of NCS. To verify the diagnosis, all children underwent computed tomography with 3D cranial reconstruction. RESULTS AND CONCLUSION: The distribution of diagnoses was as follows: scaphocephaly - 28 (50%) patients, trigonocephaly - 21 (38%), different forms of plagiocephaly - 7 (12%). On admission to the hospital, 25 (43%) patients were diagnosed with perinatal CNS damage, 10 (18%) were born premature, 33 (59%) had neurological deviations. The clinical picture of NCS was polymorphic that might explain an increase in the number of children with late diagnosed craniosynostosis. The early diagnosis of NCS which is the basis for using less invasive surgical methods is particularly important for prognosis. PMID- 26356611 TI - [The influence of hysterical symptoms on the comorbid mental disorders]. AB - OBJECTIVE: to investigate the influence of conversion-dissociative (hysterical) disorder on comorbid mental disorders. MATERIAL AND METHODS: Authors examined 154 inpatients with conversion-dissociative disorder with comorbid mental pathology. RESULTS AND CONCLUSION: Conversion-dissociative hysterical symptoms mask or mimic main clinical manifestations of comorbid mental disorders and facilitate its exacerbations and deterioration. PMID- 26356612 TI - [Augmented antipsychotic therapy with pantogam active in patients with schizophrenia]. AB - OBJECTIVE: to study the efficacy of the GABA-ergic drug pantogam active (D-, L gopantenic acid) in patients with schizophrenia treated with typical neuroleptics and to assess the rate of treatment response and tolerability of the drug. MATERIAL AND METHODS: A sample consisted of 70 patients with schizophrenia stratified into main (n=35) and control (n=35) groups. All patients received one of typical antipsychotics (haloperidol, zuclopenthixol, promazine or perphenazine). Patients of the main group received in addition pantogam active in dose of 1200-1800 mg daily. The maximum allowed dose of 1800 mg daily was used in 62.9% of the patients. RESULTS AND CONCLUSION: The long-term combined therapy with the addition of D-, L-gopantenic acid (pantogam activ) allowed to achieve clinical improvement earlier (on 8th week in the main group versus 16th week in the control group). The frequency and severity of secondary negative symptoms associated with antipsychotic therapy were decreased as well. The high efficacy and tolerability of the combined therapy allow to improve quality of life in patients with schizophrenia and their compliance to treatment as well as to reduce costs of medical care. PMID- 26356613 TI - [EEG spectral characteristics in resistant depression patients on transcranial magnetic stimulation treatment]. AB - OBJECTIVE: to examine the EEG spectral characteristics during TMS in resistant depression therapy. MATERIAL AND METHODS: The sample consisted of 32 depressive patients diagnosed with recurrent depressive disorder or bipolar affective disorder. TMS, as well as EEG, were conducted during the previous inefficient thymoanaleptic therapy with reduced doses. TMS was performed in the left prefrontal cortex. Treatment course consisted of 15 procedures with 100% threshold intensity. During a single procedure, the patient received 20 cycles of stimulation pulses with the frequency of 15 Hz, duration of 20 seconds and interval of 60 seconds between single cycles. EEG was recorded with the use of the "NEURO-KM" apparatus (Russia) with band pass from 0.5 to 45 Hz and time constant of 0.3 sec before and after the course of TMS. Spectroscopic analysis of EEG was conducted using the Fast Furies Transformation analysis with average of no less than 30 periods for 2 seconds with subsequent mapping with the use of the "BRAINSYS" system (Russia). RESULTS AND CONCLUSION: After conducting TMS, EEG changes were generalized and included the reconstruction of all frequencies of the electrical brain activity. However, the major changes were seen in alpha rhythm spectrums: its index increased in all cortical areas, mostly in the occipital cortex, thereby forming the alpha-rhythm focus in these areas. PMID- 26356614 TI - [Neurological disturbances in post-surgical patients with breast cancer]. AB - OBJECTIVE: to explore the sensory disturbances in the arm on the side of operation compared to the opposite upper extremity and evaluate quality of life in patients with breast cancer with postmastectomy syndrome. MATERIAL AND METHODS: Authors examined 110 women during one year including 64 (58.2%) with intact intercostal and shoulder nerves (group 1) and 46 (41.8%) with the nerves removed due to the progression of cancer or anatomical characteristics (group 2). We studied sensory disturbances and assessed quality of life with SF-36 questionnaire. RESULTS AND CONCLUSION: In group 1, there were less women with hyperesthesia, and quality of life level was higher compared to group 2. In group 2, the signs of hyperesthesia were more marked that may be related with the damage and/or compression of these nerves during the axillary lymphadenectomy. Preservation of intercostal and shoulder nerves during the axillary lymphadenectomy in patients with breast cancer can reduce sensory disturbances and improve quality of life of the patients. PMID- 26356615 TI - [Clinical and morphologic efficacy of a complex antioxidant and energy correction therapy of different duration in brain infarction: results of a multicenter randomized trial]. AB - AIM: To compare clinical and morphological results of treatment of ischemic stroke in three groups of patients which differed by the forms and duration of an antioxidant therapy. MATERIAL AND METHODS: A randomized clinical trial was performed in 8 vascular centers of the Russian Federation in 2010-2014. It included 373 patients with ischemic stroke in the carotid territory. Patients were randomized into 3 groups to receive different regimens of antioxidant therapy as an adjunct to standard therapy: control group (ascorbic acid; 132 patients); cytoflavin (20 ml per day for 10 days; 133 patients); cytoflavin (the dose was decreased to 10 ml per day from 11th to 20th day) (108 patients). Patient's condition was assessed in 1, 10 and 21 day by a complex of clinical, laboratory and instrumental methods. RESULTS AND CONCLUSION: The analysis of CT in 1th and 21th day revealed a significant 1,5-1,7- fold decrease in the cerebral ischemic lesion in both groups treated with cytoflavin with no significant morphologic changes in the ascorbic acid group. The percentage of patients with ischemic lesion, increased during days 1-21, was 2-fold higher in the ascorbic acid group compared to cytoflavin groups. Morphologic changes were correlated with clinical variables and outcome. In patients with >=14 points on NIH scale on admission, prolonged 20 day cytoflavin therapy was associated with a more prominent improvement of neurologic, functional and cognitive status compared to 10-day cytoflavin infusion. No differences in clinical variables were observed in patients with mild symptoms (<14 points on NIH scale on admission) receiving cytoflavin for 10 and 20 days. PMID- 26356616 TI - [Comparison of different doses of escitalopram in the prevention of dementia in patients with depression and moderate cognitive dysfunction associated with chronic brain ischemia]. AB - OBJECTIVE: to compare different doses of escitalopram (cipralex) in the prevention of dementia in patients with depression and moderate cognitive dysfunction associated with chronic brain ischemia. MATERIAL AND METHODS: Two groups of patients, aged 65-78 years, with chronic brain ischemia and mild or moderate depression with moderate cognitive dysfunction were treated with different doses of escitalopram: 30 patients received 5 mg daily during all treatment period; 42 patients - 5 mg daily during the first week and 10 mg from the second week of treatment. The treatment lasted for 6 months; the period of observation was 8 months. RESULTS AND CONCLUSION: The efficacy of escitalopram is demonstrated not only for the treatment of depression associated with cognitive dysfunction in patients with chronic brain ischemia but for decrease of the risk of dementia in long-term period. PMID- 26356617 TI - [Clinical and instrumental diagnosis of concomitant venous dysfunction of the brain and extremities]. AB - OBJECTIVE: to compare the frequency, preferential localization, severity of disturbances of venous circulation in the brain and limbs. MATERIAL AND METHODS: Authors examined 140 people during 2009-2014: 20 apparently healthy people without clinical manifestations of extra-intracerebral venous insufficiency; 70 patients with clinical and instrumental signs of venous encephalopathy; 50 patients with varicose disease. History and clinical status were studied for all patients. In addition to physical methods, dynamic teletermography and triplex study of head, neck and extremity vessels were used. RESULTS AND CONCLUSION: -A higher, than previously estimated, frequency of concomitant venous dysfunction of the brain and other locations was identified. It has been shown that venous insufficiency is a systemic pathology that affects venous circulation of the brain and extremities. PMID- 26356618 TI - [Biomarkers in children with traumatic brain injury]. AB - OBJECTIVE: to study the content of biomarkers of diagnostic and prognostic value in the assessment of traumatic brain injury (TBI) severity in children. MATERIAL AND METHODS: Authors determined the levels of glial protein S100B, neuronspecific enolase (NSE), autoantibodies (aAb) to glutamate receptors and natural autoantibodies (nAb) to S100B and brain-derived neurotrophic factor (BDNF) in serum/plasma of children with different outcomes of TBI. All parameters were analyzed in the 1-3rd, 7-8th, 14-15th and 20-23rd days after TBI, and, in some cases of severe brain injury and long stay patients in hospital, in 11-12 months after TBI. The severity and outcome of TBI were assessed according the Glasgow coma scale (GCS) and the Glasgow outcome scale (GOS), respectively. RESULTS AND CONCLUSION: The content of NSE and S100B increased immediately after TBI regardless of TBI severity, but in cases with favorable outcome it dropped to a normal level in the first 3 days. The maximum levels of S100B protein and NSE were observed in children with fatal TBI, and higher values were observed throughout the post-traumatic period. The low levels of aAb to NR2-subtype of glutamate receptors that were similar to controls and the high level of nAb to S100B in the first days after severe TBI indicate the failure of compensatory adaptive immunological mechanisms and the high permeability of the brain-blood barrier, which were poor prognostic signs for children with severe TBI. Mild and severe TBI with full recovery were accompanied by higher values of VDNF in the 1st day followed by a decline to the 3rd day. The level of BDNF in the 1st day of TBI was the lowest and subsequently continued to decline in patients with severe TBI with fatal outcome. PMID- 26356619 TI - [The relationship between neuroendocrine dysfunction and free-radical oxidation in old age alcoholism]. AB - OBJECTIVE: to study the relationship between dysfunction of the hypothalamic pituitary-adrenal (HPA) axis and free-radical oxidation in old age alcoholism. MATERIAL AND METHODS: Authors examined 46 men and women, aged 60-80 years, with alcoholism. Contents of cortisol, lipid peroxidation products and the level of an oxidatively modified protein were measured. RESULTS AND CONCLUSION: A decrease in blood cortisol content and correlations between its level and activity of free radical oxidation were identified. The severity of neuroendocrine dysfunction in old patients was sex-related. It has been suggested that the impairment of HPA system activity may be a cause of oxidative stress and development of alcoholism. PMID- 26356620 TI - [Incidence of alcoholic psychoses, mortality from alcoholic poisonings and diseases of the liver and in Russia]. AB - Authors studied the influence of availability of beer on mortality from alcoholic poisonings, diseases of a liver and incidence of alcoholic psychoses in Russia during 1995-2011. Time series analysis was performed using the method of ARIMA. There were no significant associations between the availability of beer and levels of mortality and morbidity. PMID- 26356621 TI - [Intravenous immunoglobulin in treatment of autoimmune neurological diseases in children]. AB - Though the mechanisms of action of intravenous immunoglobulins (IVIG) are not completely understood, these drugs are widely used in treatment of autoimmune diseases. In this review, we have analyzed the literature on the use of IVIG in the treatment of autoimmune diseases of the nervous system in children and discuss the management of patients basing on the recommendation of the European Federation of Neurological Societies. The efficacy of IVIG in children has been shown as first line treatment in Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy, dermatomyositis as a second-line drug in the combination with prednisolone or immunosuppressors in patients refractory to treatment with corticosteroids and cytostatics, myasthenic crisis in myasthenia gravis, exacerbations and short-term treatment of severe forms, non-responsiveness to acetylcholinesterase inhibitors, multiple sclerosis as second or third line of treatment in patients with relapsing-remitting course with intolerance to standard immunomodulatory therapy, acute multiple encephalomyelitis with no response to the treatment with high doses of corticosteroids, paraneoplastic syndromes, pharmacoresistant epilepsy and autoimmune encephalitis. Because the right choice of the drug plays a key role, in particular, in children, that determines the efficacy and safety of the treatment, we present the main approaches to the choice of the drug and schemes of treatment of autoimmune diseases of the nervous system in children. PMID- 26356622 TI - [N-acetylaspartate is a biomarker of psychiatric and neurological disorders]. AB - N-acetylaspartate (NAA) is an amino acid abundant in the brain and claimed the role of a biomarker of neuropsychiatric disorders. The basic ways of NAA concentration measurement in the brain are magnetic resonance spectroscopy (MRS), magnetic resonance imaging (MRI) and chromatography. The review examined the relationship between NAA concentrations in different parts of the brain and biological liquids and neuropsychiatric disorders. PMID- 26356623 TI - [Cortexin. Molecular mechanisms and targets of neuroprotective activity]. AB - Neurotrophic drug cortexin, a lyophilized extraction of animal cortex, comprises neuropeptides, amino acids and trace elements. The nucleoprotein complexes of the cerebral cortex can also retain elements of chromatin with DNA fragments. All of these components of cortexin have a specific range of "targets" for the specific correction of the molecular and cellular processes at various stages of the pathological process. A modern concept of neurosignaling considers the associated processes - from the synaptic level to the epigenetic patterns of neuron nucleus, in which an important place belongs to corrective peptide molecules. Peptide components of cortexin derived from the animal brain, which interact with cellular and molecular "targets", provide a new view on mechanisms of neuroprotection. PMID- 26356624 TI - [From the conception of "oxidizing stress" to the conception of "cell signaling modulation"]. AB - We discuss the current conception of "oxidizing stress" which covers a wide group of various interrelated phenomena including higher production of reactive oxygen species (ROS) and oxidative damage of cellular molecular components. Currently the term of oxidizing stress is used for the description of pro-oxidant and antioxidant imbalance, with the prevalence of the former, that results in the damage of biological molecules and cellular structures. However ROS do not play a single role in oxidative metabolism. There are also active nitrogen forms, reactive forms of carbon, chlorine and sulphur. These highly reactive molecules are involved in many reactions and play a great role in the regulation of different metabolic processes in the body. These reactions underlie such pathological processes as heart ischemia, atherosclerosis, cerebral ischemia and different types of inflammation. An effect of highly reactive molecules on the destruction of biologically important molecular in different stressful conditions is determined by the reactions they are involved in. But the balance of oxidizers and antioxidants should not be considered as a unified system because main cellular redox systems are not in the redox equilibrium. In this view, a search for an optimal oxidizer that impacts on the modulation of cellular signal pathways related with ROS development is the most effective way in the development of antioxidant therapy. PMID- 26356625 TI - Portuguese Family Physicians' Awareness of Diagnostic and Laboratory Test Costs: A Cross-Sectional Study. AB - BACKGROUND: Physicians' ability to make cost-effective decisions has been shown to be affected by their knowledge of health care costs. This study assessed whether Portuguese family physicians are aware of the costs of the most frequently prescribed diagnostic and laboratory tests. METHODS: A cross-sectional study was conducted in a representative sample of Portuguese family physicians, using computer-assisted telephone interviews for data collection. A Likert scale was used to assess physician's level of agreement with four statements about health care costs. Family physicians were also asked to estimate the costs of diagnostic and laboratory tests. Each physician's cost estimate was compared with the true cost and the absolute error was calculated. RESULTS: One-quarter (24%; 95% confidence interval: 23%-25%) of all cost estimates were accurate to within 25% of the true cost, with 55% (95% IC: 53-56) overestimating and 21% (95% IC: 20 22) underestimating the true actual cost. The majority (76%) of family physicians thought they did not have or were uncertain as to whether they had adequate knowledge of diagnostic and laboratory test costs, and only 7% reported receiving adequate education. The majority of the family physicians (82%) said that they had adequate access to information about the diagnostic and laboratory test costs. Thirty-three percent thought that costs did not influence their decision to order tests, while 27% were uncertain. CONCLUSIONS: Portuguese family physicians have limited awareness of diagnostic and laboratory test costs, and our results demonstrate a need for improved education in this area. Further research should focus on identifying whether interventions in cost knowledge actually change ordering behavior, in identifying optimal methods to disseminate cost information, and on improving the cost-effectiveness of care. PMID- 26356626 TI - Sex-Specific Effects of Progesterone on Early Outcome of Intracerebral Hemorrhage. AB - BACKGROUND: Preclinical evidence suggests that progesterone improves recovery after intracerebral hemorrhage (ICH); however, gonadal hormones have sex-specific effects. Therefore, an experimental model of ICH was used to assess recovery after progesterone administration in male and female rats. METHODS: ICH was induced in male and female Wistar rats via stereotactic intrastriatal injection of clostridial collagenase (0.5 U). Animals were randomized to receive vehicle or 8 mg/kg progesterone intraperitoneally at 2 h, then subcutaneously at 5, 24, 48, and 72 h after injury. Outcomes included relevant physiology during the first 3 h, hemorrhage and edema evolution over the first 24 h, proinflammatory transcription factor and cytokine regulation at 24 h, rotarod latency and neuroseverity score over the first 7 days, and microglial activation/macrophage recruitment at 7 days after injury. RESULTS: Rotarod latency (p = 0.001) and neuroseverity score (p = 0.01) were improved in progesterone-treated males, but worsened in progesterone-treated females (p = 0.028 and p = 0.008, respectively). Progesterone decreased cerebral edema (p = 0.04), microglial activation/macrophage recruitment (p < 0.001), and proinflammatory transcription factor phosphorylated nuclear factor-x03BA;B p65 expression (p = 0.0038) in males but not females, independent of tumor necrosis factor-alpha, interleukin-6, and toll-like receptor-4 expression. Cerebral perfusion was increased in progesterone treated males at 4 h (p = 0.043) but not 24 h after injury. Hemorrhage volume, arterial blood gases, glucose, and systolic blood pressure were not affected. CONCLUSIONS: Progesterone administration improved early neurobehavioral recovery and decreased secondary neuroinflammation after ICH in male rats. Paradoxically, progesterone worsened neurobehavioral recovery and did not modify neuroinflammation in female rats. Future work should isolate mechanisms of sex specific progesterone effects after ICH. PMID- 26356627 TI - Silver(I)-Catalyzed N-Trifluoroethylation of Anilines and O-Trifluoroethylation of Amides with 2,2,2-Trifluorodiazoethane. AB - A straightforward N-trifluoroethylation of anilines has been developed based on silver-catalyzed N-H insertions with 2,2,2-trifluorodiazoethane (CF3CHN2). Mechanistically, the reaction is proposed to involve migratory insertion of a silver carbene as the key step. In contrast, when amides are employed as the substrates under similar reaction conditions, O-trifluoroethylation occurs to afford trifluoroethyl imidates. PMID- 26356628 TI - Phenacyl Ethyl Carbazolium as a Long Wavelength Photoinitiator for Free Radical Polymerization. AB - A new phenacyl-type photoinitiator based on ethyl carbazole as a long wavelength photo-initiator is developed for free radical polymerization. Phenacyl ethyl carbazolium hexafluoroantimonate (PECH) photoinitiator is synthesized in a two step, one-pot manner by quaternizing ethyl carbazole with phenacyl bromide and subsequent ion exchange reaction with potassium hexafluoroantimonate. Under irradiation, PECH tends to undergo homolytic bond cleavage bringing about initiating free radicals. However, as evidenced by cyclic voltammetry and real time photobleaching studies, formation of initiating cationic species is highly unlikely as the photochemically formed charged carbazole units tend to couple. PMID- 26356630 TI - Structural neighboring property for identifying protein-protein binding sites. AB - BACKGROUND: The protein-protein interaction plays a key role in the control of many biological functions, such as drug design and functional analysis. Determination of binding sites is widely applied in molecular biology research. Therefore, many efficient methods have been developed for identifying binding sites. In this paper, we calculate structural neighboring property through Voronoi diagram. Using 6,438 complexes, we study local biases of structural neighboring property on interface. RESULTS: We propose a novel statistical method to extract interacting residues, and interacting patches can be clustered as predicted interface residues. In addition, structural neighboring property can be adopted to construct a new energy function, for evaluating docking solutions. It includes new statistical property as well as existing energy items. Comparing to existing methods, our approach improves overall F(nat) value by at least 3%. On Benchmark v4.0, our method has average I(rmsd) value of 3.31A and overall F(nat) value of 63%, which improves upon I(rmsd) of 3.89 A and F(nat) of 49% for ZRANK, and I(rmsd) of 3.99A and F(nat) of 46% for ClusPro. On the CAPRI targets, our method has average I(rmsd) value of 3.46 A and overall F(nat) value of 45%, which improves upon I(rmsd) of 4.18 A and F(nat) of 40% for ZRANK, and I(rmsd) of 5.12 A and F(nat) of 32% for ClusPro. CONCLUSIONS: Experiments show that our method achieves better results than some state-of-the-art methods for identifying protein-protein binding sites, with the prediction quality improved in terms of CAPRI evaluation criteria. PMID- 26356632 TI - How to Turn On an Ancient Metabolic Enzyme? Add Insulin and Deacetylate. PMID- 26356631 TI - Protein-polymer conjugation-moving beyond PEGylation. AB - In this review, we summarize-from a materials science perspective-the current state of the field of polymer conjugates of peptide and protein drugs, with a focus on polymers that have been developed as alternatives to the current gold standard, poly(ethylene glycol) (PEG). PEGylation, or the covalent conjugation of PEG to biological therapeutics to improve their therapeutic efficacy by increasing their circulation half-lives and stability, has been the gold standard in the pharmaceutical industry for several decades. After years of research and development, the limitations of PEG, specifically its non-degradability and immunogenicity have become increasingly apparent. While PEG is still currently the best polymer available with the longest clinical track record, extensive research is underway to develop alternative materials in an effort to address these limitations of PEG. Many of these alternative materials have shown promise, though most of them are still in an early stage of development and their in vivo distribution, mechanism of degradation, route of elimination and immunogenicity have not been investigated to a similar extent as for PEG. Thus, further in-depth in vivo testing is essential to validate whether any of the alternative materials discussed in this review qualify as a replacement for PEG. PMID- 26356633 TI - Validation of the Italian version of the Compensatory Eating and Behaviors in Response to Alcohol Consumption Scale (CEBRACS). AB - The aim of the study was to evaluate, in a representative sample of high school students, the psychometric characteristics of the Italian version of the CEBRACS scale (Rahal et al., 2011), a questionnaire investigating compensatory eating behaviors correlated with alcohol consumption. These behaviors are adopted to make up for calories consumed through the drinking of alcohol and/or to enhance the intoxicative effects of alcohol. Study participants were selected from an initial sample of 965 students. Out of the 965 youths originally recruited, 640 (376 males and 264 females) reported drinking alcohol over the previous 3 months, and were considered eligible for the purpose of the study. The following questionnaires were administered: CEBRACS, Alcohol Use Disorders Identification Test (AUDIT) (Saunders, 1993), and the Eating Disorder Inventory-3 (EDI-3) (Garner, 2004). Test/retest reproducibility was evaluated on a subgroup of 189 youths. The factorial structure, internal consistency, test-retest reliability and concurrent validity of CEBRACS were evaluated. Factor analysis of inter-item correlation indicated 5 factors as being better suited to describe data, with an estimated 68.85% variance: "Alcohol Effect, "Laxative Use", "Dietary Restraint and Exercise", "Diuretic Use", "Restriction and Vomiting". A high degree of reproducibility and homogeneity (ICC = 0.806; Cronbach's Alpha = 0.886) of the scale was detected. A significant correlation was revealed between CEBRACS, the three eating disorder risk scales comprised in EDI-3 and scores and clinical risk yielded by AUDIT. The overall reliability and validity of the CEBRACS scale was confirmed in an extensive sample of Italian students, highlighting a satisfactory construct validity, good internal consistency and good degree of reproducibility. In view of the relevance of the problem, associated with serious health risks, a more widespread investigation of the phenomenon should be conducted using evaluation tools of proven validity and reliability on both representative samples of the general population and clinical samples. PMID- 26356635 TI - Impact of the Multi-Gene ThyroSeq Next-Generation Sequencing Assay on Cancer Diagnosis in Thyroid Nodules with Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance Cytology. AB - BACKGROUND: Fine-needle aspiration (FNA) cytology is a common approach to evaluate thyroid nodules. It offers definitive diagnosis of a benign or malignant nodule in the majority of cases. However, 10-25% of nodules yield one of three indeterminate cytologic diagnoses, leading to suboptimal management of these patients. Atypia of undetermined significance/follicular lesion of undermined significance (AUS/FLUS) is a common indeterminate diagnosis, with the cancer risk ranging from 6% to 48%. This study assessed whether a multi-gene next-generation sequencing (NGS) assay can offer significant improvement in diagnosis in AUS/FLUS nodules. METHODS: From May 2014 to March 2015, 465 consecutive FNA samples with the cytologic diagnosis of AUS/FLUS underwent prospective molecular testing using the ThyroSeq v2.1 panel. The panel included 14 genes analyzed for point mutations and 42 types of gene fusions occurring in thyroid cancer. In addition, eight genes were assessed for expression in order to evaluate the cell composition of FNA samples. Ninety-eight (21%) of these nodules had definitive surgical (n = 96) or nonsurgical (n = 2) follow-up and were used to determine the assay performance. RESULTS: Among 465 AUS/FLUS nodules, three were found to be composed of parathyroid cells and 462 of thyroid follicular cells. Of the latter, 31 (6.7%) were positive for mutations. The most frequently mutated genes were NRAS and HRAS, and overall point mutations in seven different genes and five types of gene fusions were identified in these nodules. Among 98 nodules with known outcome, histologic analysis revealed 22 (22.5%) cancers. ThyroSeq v2.1 was able to classify 20/22 cancers correctly, showing a sensitivity of 90.9% [confidence interval (CI) 78.8-100], specificity of 92.1% [CI 86.0-98.2], positive predictive value of 76.9% [CI 60.7-93.1], and negative predictive value of 97.2% [CI 78.8 100], with an overall accuracy of 91.8% [CI 86.4-97.3]. CONCLUSIONS: The results of the study demonstrate that the ThyroSeq v2.1 multi-gene NGS panel of molecular markers provides both high sensitivity and high specificity for cancer detection in thyroid nodules with AUS/FLUS cytology, which should allow improved management for these patients. PMID- 26356634 TI - Drug Induced Liver Injury: Review with a Focus on Genetic Factors, Tissue Diagnosis, and Treatment Options. AB - Drug-induced liver injury (DILI) is a rare but potentially life threatening adverse drug reaction. DILI may mimic any morphologic characteristic of acute or chronic liver disease, and the histopathologic features of DILI may be indistinguishable from those of other causes of liver injury, such as acute viral hepatitis. In this review article, we provide an update on causative agents, clinical features, pathogenesis, diagnosis modalities, and outcomes of DILI. In addition, we review results of recently reported genetic studies and updates on pharmacological and invasive treatments. PMID- 26356636 TI - Novel Strategy for Tracking the Microbial Degradation of Azo Dyes with Different Polarities in Living Cells. AB - Direct visualization evidence is important for understanding the microbial degradation mechanisms. To track the microbial degradation pathways of azo dyes with different polar characterizations, sensors based on the fluorescence resonance energy transfer (FRET) from 1,8-naphthalimide to azo dyes were synthesized, in which the quenched fluorescence will recover when the azo bond was cleaved. In living cells, the sensor-tracking experiment showed that the low polarity and hydrophobic azo dye can be taken up into the cells and reduced inside the cells, whereas the high polarity and hydrophilic azo dye can be reduced only outside the cells because of the selective permeability of the cell membranes. These results indicated that there were two different bacterial degradation pathways available for different polarity azo dyes. To our knowledge, no fluorescent sensor has yet been designed for illuminating the microbial degradation mechanisms of organic pollutants with different characteristics. PMID- 26356637 TI - A Professional Journey Through Life. AB - In response to the request to write about those changes that have occurred in my professional outlook and practice that have come with age, I have recounted some of the experiences I have had that seem to have contributed to these changes. There are a couple of important themes that have run through my professional experiences as a therapist, supervisor, teacher, and researcher. One of the themes has to do with my psychotherapy orientation. The other involves the tension that I have experienced between research and practice. I begin by discussing each of these, and then go on to highlight some of the more general lessons learned over the years, including coming to be more myself as a therapist, developing a broader perspective on life, being more clinically integrative, and learning to be accepting of what therapy can and cannot do. PMID- 26356638 TI - Chronic Compression of the Dorsal Root Ganglion Enhances Mechanically Evoked Pain Behavior and the Activity of Cutaneous Nociceptors in Mice. AB - Radicular pain in humans is usually caused by intraforaminal stenosis and other diseases affecting the spinal nerve, root, or dorsal root ganglion (DRG). Previous studies discovered that a chronic compression of the DRG (CCD) induced mechanical allodynia in rats and mice, with enhanced excitability of DRG neurons. We investigated whether CCD altered the pain-like behavior and also the responses of cutaneous nociceptors with unmyelinated axons (C-fibers) to a normally aversive punctate mechanical stimulus delivered to the hairy skin of the hind limb of the mouse. The incidence of a foot shaking evoked by indentation of the dorsum of foot with an aversive von Frey filament (tip diameter 200 MUm, bending force 20 mN) was significantly higher in the foot ipsilateral to the CCD surgery as compared to the contralateral side on post-operative days 2 to 8. Mechanically evoked action potentials were electrophysiologically recorded from the L3 DRG, in vivo, from cell bodies visually identified as expressing a transgenically labeled fluorescent marker (neurons expressing either the receptor MrgprA3 or MrgprD). After CCD, 26.7% of MrgprA3+ and 32.1% MrgprD+ neurons exhibited spontaneous activity (SA), while none of the unoperated control neurons had SA. MrgprA3+ and MrgprD+ neurons in the compressed DRG exhibited, in comparison with neurons from unoperated control mice, an increased response to the punctate mechanical stimuli for each force applied (6, 20, 40, and 80 mN). We conclude that CCD produced both a behavioral hyperalgesia and an enhanced response of cutaneous C-nociceptors to aversive punctate mechanical stimuli. PMID- 26356640 TI - The ratio of change in muscle thickness between superficial and deep cervical flexor muscles during the craniocervical flexion test and a suggestion regarding clinical treatment of patients with musculoskeletal neck pain. AB - [Purpose] The purpose of this study was to identify the imbalance of muscle recruitment in cervical flexor muscles during the craniocervical flexion test by using ultrasonography and to propose the optimal level of pressure in clinical craniocervical flexion exercise for people with neck pain. [Subjects and Methods] A total of 18 students (9 males and 9 females) with neck pain at D University in Gyeongsangbuk-do, South Korea, participated in this study. The change in muscle thickness in superficial and deep cervical flexor muscles during the craniocervical flexion test was measured using ultrasonography. The ratio of muscle thickness changes between superficial and deep muscles during the test were obtained to interpret the imbalance of muscle recruitment in cervical flexor muscles. [Results] The muscle thickness ratio of the sternocleidomastoid muscle/deep cervical flexor muscles according to the incremental pressure showed significant differences between 22 mmHg and 24 mmHg, between 24 mmHg and 28 mmHg, between 24 mmHg and 30 mmHg, and between 26 mmHg and 28 mmHg. [Conclusion] Ultrasonography can be applied for examination of cervical flexor muscles in clinical environment, and practical suggestion for intervention exercise of craniocervical flexors can be expected on the pressure level between 24 mmHg and 26 mmHg enabling the smallest activation of the sternocleidomastoid muscle. PMID- 26356639 TI - Comparing Effects of Biologic Agents in Treating Patients with Rheumatoid Arthritis: A Multiple Treatment Comparison Regression Analysis. AB - Rheumatoid arthritis patients have been treated with disease modifying anti rheumatic drugs (DMARDs) and the newer biologic drugs. We sought to compare and rank the biologics with respect to efficacy. We performed a literature search identifying 54 publications encompassing 9 biologics. We conducted a multiple treatment comparison regression analysis letting the number experiencing a 50% improvement on the ACR score be dependent upon dose level and disease duration for assessing the comparable relative effect between biologics and placebo or DMARD. The analysis embraced all treatment and comparator arms over all publications. Hence, all measured effects of any biologic agent contributed to the comparison of all biologic agents relative to each other either given alone or combined with DMARD. We found the drug effect to be dependent on dose level, but not on disease duration, and the impact of a high versus low dose level was the same for all drugs (higher doses indicated a higher frequency of ACR50 scores). The ranking of the drugs when given without DMARD was certolizumab (ranked highest), etanercept, tocilizumab/ abatacept and adalimumab. The ranking of the drugs when given with DMARD was certolizumab (ranked highest), tocilizumab, anakinra/rituximab, golimumab/ infliximab/ abatacept, adalimumab/ etanercept [corrected]. Still, all drugs were effective. All biologic agents were effective compared to placebo, with certolizumab the most effective and adalimumab (without DMARD treatment) and adalimumab/ etanercept (combined with DMARD treatment) the least effective. The drugs were in general more effective, except for etanercept, when given together with DMARDs. PMID- 26356641 TI - The roles and clinical significance of microRNAs in cervical cancer. AB - Cervical carcinogenesis induced by persistent human papillomavirus (HPV) infection represents a stepwise progression from precursors to invasive cervical cancer. Accumulated evidence has shown aberrant expression of microRNAs (miRNAs) in cervical cancer tissues and cells. Further studies reveal that miRNAs play key roles in the initiation and progression of cervical cancer, via specific signaling pathways, including E6-p53, E7-pRb, phosphoinositide-3 kinase (PI3K) Akt, Notch, Wnt/beta-catenin, and Hedgehog pathways. Some studies demonstrate that miRNAs might serve as biomarkers or therapeutic targets, presenting a potential prospect in clinical practice. All results provide new insights into the function of miRNAs and the pathogenesis of cervical cancer induced by viral oncoproteins. New approaches for miRNA-based prevention and management for cervical cancer will be developed in the future. PMID- 26356642 TI - Parallelized patient-specific quality assurance for high-dose-rate image-guided brachytherapy in an integrated computed tomography-on-rails brachytherapy suite. AB - PURPOSE: To describe a parallelized patient-specific quality assurance (QA) program designed to ensure safety and quality in image-guided high-dose-rate brachytherapy in an integrated computed tomography (CT)-on-rails brachytherapy suite. MATERIALS AND METHODS: A patient-specific QA program has been modified for the image-guided brachytherapy (IGBT) program in an integrated CT-on-rails brachytherapy suite. In the modification of the QA procedures of Task Group-59, the additional patient-specific QA procedures are included to improve rapid IGBT workflow with applicator placement, imaging, planning, treatment, and applicator removal taking place in one room. RESULTS: The IGBT workflow is partitioned into two groups of tasks that can be performed in parallel by two or more staff members. One of the unique components of our implemented workflow is that groups work together to perform QA steps in parallel and in series during treatment planning and contouring. Coordinating efforts in this systematic way enable rapid and safe brachytherapy treatment while incorporating 3-dimensional anatomic variations between treatment days. CONCLUSIONS: Implementation of these patient specific QA procedures in an integrated CT-on-rails brachytherapy suite ensures confidence that a rapid workflow IGBT program can be implemented without sacrificing patient safety or quality and deliver highly-conformal dose to target volumes. These patient-specific QA components may be adapted to other IGBT environments that seek to provide rapid workflow while ensuring quality. PMID- 26356643 TI - Investigation of effect of leg support elevation timing on the horizontal force acting on the buttocks in a reclining wheelchair. AB - [Purpose] The purpose of this study was to investigate the effect of the timing of leg support elevation on the horizontal force acting on the buttocks in a reclining wheelchair. [Subjects and Methods] The participants were 17 healthy men. Two experimental conditions were tested: the leg-down and leg-up conditions. The back support was reclined at increasing angles, from the initial upright position (IUP), proceeding to the fully reclined position (FRP), and returned to the upright position (RUP). The posterior inclination phase was from IUP to FRP, and the returning inclination phase was from FRP to RUP. [Results] The horizontal force under the leg-up condition was significantly higher than that under the leg down condition in all positions of back support. [Conclusion] The leg supports should be positioned downward before reclining the back support of a wheelchair. PMID- 26356644 TI - Relationship Between Physical Qualities and Minutes Played in International Women's Rugby Sevens. AB - PURPOSE: To investigate the physical qualities that differentiate playing minutes in international-level women's rugby sevens players. METHODS: Twenty-four national-level female rugby sevens players underwent measurements of anthropometry, acceleration, speed, lower- and upper-body strength, lower-body power, and aerobic fitness. Playing minutes in international competition were used to differentiate players into 2 groups, a high- or low-playing-minutes group. Playing minutes were related to team selection, which was determined by the coaching staff. Playing minutes were therefore used to differentiate performance levels. RESULTS: Players in the high-playing-minutes group (>=70 min) were older (mean +/- SD 24.3 +/- 3.1 vs 21.2 +/- 4.3 y, P = .05, effect size [ES] = 0.77 +/- 0.66, 90% confidence limit) and had greater experience in a national training-center environment (2.4 +/- 0.8 vs 1.7 +/- 0.9 y, P = .03, ES = 0.83 +/- 0.65), faster 1600-m time (374.5 +/- 20.4 vs 393.5 +/- 29.8 s, P = .09, ES = 0.70 +/- 0.68), and greater 1-repetition-maximum upper-body strength (bench press 68.4 +/- 6.3 vs 62.2 +/- 8.1 kg, P = .07, ES = 0.80 +/- 0.70, and neutral-grip pull-up 84.0 +/- 8.2 vs 79.1 +/- 5.4 kg, P = .12, ES = 0.68 +/- 0.72) than athletes who played fewer minutes. Age (rs = .59 +/- ~.28), training experience (rs = .57 +/- ~.29), bench press (r = .44 +/- ~.36), and 1600-m time (r = -.43 +/ ~.34) were significantly associated with playing minutes. Neutral-grip pull-up and bench press contributed significantly to a discriminant analysis. The average squared canonical correlation was .46. The discriminant analysis predicted 7 of 9 and 6 of 10 high- and low-playing-minutes athletes, respectively. CONCLUSIONS: Age, training experience, upper-body strength, and aerobic fitness differentiated athlete playing minutes in international women's rugby sevens. PMID- 26356645 TI - An Update on Treatment of Drug-Induced Liver Injury. AB - Drug-induced liver injury (DILI) has been linked to more than 1,000 medications and remains the most common cause of acute liver failure in the United States. Here, we review the most current literature regarding treatment and make recommendations for the management of this relatively common disease. Since treatment of DILI remains largely elusive, recent studies have attempted to define new management strategies for these difficult patients. Early diagnosis and withdrawal of the suspected medication is the mainstay of treatment of DILI. For acetaminophen and Amanita mushroom poisoning, there are specific therapies in use. Finally, there are other possible management modalities for DILI, including corticosteroids and ursodeoxycholic acid. PMID- 26356646 TI - Bioconcentration, metabolism and half-life time of the human therapeutic drug diltiazem in rainbow trout Oncorhynchus mykiss. AB - Diltiazem is a human therapeutic drug and a member of the group of calcium channel blockers having widespread use in the treatment of angina pectoris and hypertension. The objective of the present study was to assess the bioconcentration, metabolism, and half-life time of diltiazem in rainbow trout Oncorhynchus mykiss. Juvenile trout were exposed for 21 and 42 days to three nominal concentrations of diltiazem: 0.03 ug L(-1) (environmentally relevant concentration), 3 ug L(-1), and 30 ug L(-1) (sub-lethal concentrations). The bioconcentration factor (BCF) of diltiazem was relatively low (0.5-194) in analysed tissues, following the order kidney > liver > muscle > blood plasma. The half-life of diltiazem in liver, kidney, and muscle was 1.5 h, 6.2 h, and 49 h, respectively. The rate of metabolism for diltiazem in liver, kidney, muscle, and blood plasma was estimated to be 85 +/- 9%, 64 +/- 14%, 46 +/- 6%, and 41 +/- 8%, respectively. Eight diltiazem metabolites were detected. The presence of desmethyl diltiazem (M1), desacetyl diltiazem (M2), and desacetyl desmethyl diltiazem (M3) suggests that rainbow trout metabolize diltiazem mainly via desmethylation and desacetylation, similar to mammals. In addition, diltiazem undergoes hydroxylation in fish. At environmentally relevant concentrations, diltiazem and its metabolites were identified in liver and kidney, indicating the potential for uptake and metabolism in non-target organisms in the aquatic environment. PMID- 26356647 TI - Treatment of Hepatitis C Virus Infection in Children Less than 12 Years of Age in Developing Countries. AB - The treatment of hepatitis c virus (HCV) infection in children is difficult as few options are available. The standard therapy is combination pegylated interferon (PEG-IFN) alpha-2a or 2b and ribavirin, and the duration of therapy depends on HCV genotype. New oral drug therapies available for adults have still not been approved for treatment in children. Here, we review the causes of HCV infection in children, the therapeutic options for children, and the side effects of these treatments. The problems faced by physicians managing HCV infection in children less than 12 years of age in a developing country are also discussed. PMID- 26356648 TI - Practice Variation in Single-Ventricle Patients Undergoing Elective Cardiac Catheterization: A Report from the Congenital Cardiac Catheterization Project on Outcomes (C3PO). AB - OBJECTIVE: The objective of this study was to investigate variation in practice surrounding elective cardiac catheterization in patients with single-ventricle (SV) congenital heart disease. DESIGN: Patient and procedural characteristics and outcomes during SV catheterization were collected prospectively from eight centers using a web-based registry (Congenital Cardiac Catheterization Project on Outcomes). We attempted to identify a population of elective procedures by limiting the cohort in case type and timing. Cases were then stratified by stage of SV palliation (pre-bidirectional cavopulmonary anastomosis [pre-BCPA], pre Fontan and post-Fontan) and limited by age. Subcohort analysis was performed by mode of airway management (assisted vs. spontaneous ventilation). Institutional variation was assessed. RESULTS: Between 2/2007 and 6/2010, 1459 (10.1%) of 14 467 cases in the registry met the inclusion and exclusion criteria, including 326 pre-BCPA, 571 pre-Fontan and 562 post-Fontan procedures. Median patient age was 0.4 (interquartile range 0.3, 0.5), 2.6 (1.0, 3.4) and 9.6 (5.2, 15.4) years and weight was 5.6 (4.8, 6.4), 12.2 (10.5, 14), and 26.3 (16.6, 51.8) kg in the pre BCPA, pre-Fontan and post-Fontan cohorts, respectively. Cases were more commonly diagnostic in the pre-BCPA cohort (57%) whereas they were more commonly interventional in the pre-Fontan (69%) and post-Fontan (77%) cohorts. At least one adverse event (AE) occurred in 210 cases (14.4%) overall, including 20% of pre-BCPA, 11% of pre-Fontan and 14% of post-Fontan catheterizations. Mode of airway management was associated with statistically significant, but clinically small differences in hemodynamic measures in the pre- and post-Fontan cohorts, but not in the pre-BCPA group. Considerable practice variation exists across centers with variability in airway management, AE rate, case type, interventions performed and fluoroscopy time, in all SV cohorts. CONCLUSIONS: Elective catheterization in SV patients, frequently performed with intervention, is common among US congenital cardiac centers. However, important variation in practice exists during these procedures in SV patients, at all stages of palliation. PMID- 26356649 TI - Deltoid Ligament and Tibiofibular Syndesmosis Injury in Chronic Lateral Ankle Instability: Magnetic Resonance Imaging Evaluation at 3T and Comparison with Arthroscopy. AB - OBJECTIVE: To evaluate the prevalence of deltoid ligament and distal tibiofibular syndesmosis injury on 3T magnetic resonance imaging (MRI) in patients with chronic lateral ankle instability (CLAI). MATERIALS AND METHODS: Fifty patients (mean age, 35 years) who had undergone preoperative 3T MRI and surgical treatment for CLAI were enrolled. The prevalence of deltoid ligament and syndesmosis injury were assessed. The complexity of lateral collateral ligament complex (LCLC) injury was correlated with prevalence of deltoid or syndesmosis injuries. The diagnostic accuracy of ankle ligament imaging at 3T MRI was analyzed using arthroscopy as a reference standard. RESULTS: On MRI, deltoid ligament injury was identified in 18 (36%) patients as follows: superficial ligament alone, 9 (50%); deep ligament alone 2 (11%); and both ligaments 7 (39%). Syndesmosis abnormality was found in 21 (42%) patients as follows: anterior inferior tibiofibular ligament (AITFL) alone, 19 (90%); and AITFL and interosseous ligament, 2 (10%). There was no correlation between LCLC injury complexity and the prevalence of an accompanying deltoid or syndesmosis injury on both MRI and arthroscopic findings. MRI sensitivity and specificity for detection of deltoid ligament injury were 84% and 93.5%, and those for detection of syndesmosis injury were 91% and 100%, respectively. CONCLUSION: Deltoid ligament or syndesmosis injuries were common in patients undergoing surgery for CLAI, regardless of the LCLC injury complexity. 3T MRI is helpful for the detection of all types of ankle ligament injury. Therefore, careful interpretation of pre-operative MRI is essential. PMID- 26356651 TI - Client Centeredness and Health Reform: Key Issues for Occupational Therapy. AB - Health reform promotes the delivery of patient-centered care. Occupational therapy's rich history of client-centered theory and practice provides an opportunity for the profession to participate in the evolving discussion about how best to provide care that is truly patient centered. However, the growing emphasis on patient-centered care also poses challenges to occupational therapy's perspectives on client-centered care. We compare the conceptualizations of client centered and patient-centered care and describe the current state of measurement of client-centered and patient-centered care. We then discuss implications for occupational therapy's research agenda, practice, and education within the context of patient-centered care, and propose next steps for the profession. PMID- 26356652 TI - Occupational Therapy: Meeting the Needs of Families of People With Autism Spectrum Disorder. AB - Occupational therapy has much to offer to families of people with autism spectrum disorder (ASD). However, people outside the profession may be unaware of occupational therapy's breadth and scope. It is our responsibility and our duty to express the full range of occupational therapy services through research, clinical practice, advocacy, and consumer education. This special issue of the American Journal of Occupational Therapy, with its focus on autism, embarks on this endeavor by highlighting research and theoretical articles that address the various aspects of occupational therapy practice that can help to fully meet the needs of people with ASD and their families. PMID- 26356653 TI - Effectiveness of Interventions to Improve Social Participation, Play, Leisure, and Restricted and Repetitive Behaviors in People With Autism Spectrum Disorder: A Systematic Review. AB - People with autism spectrum disorder (ASD) commonly experience difficulties with social participation, play, and leisure along with restricted and repetitive behaviors that can interfere with occupational performance. The objective of this systematic review was to evaluate current evidence for interventions within the occupational therapy scope of practice that address these difficulties. Strong evidence was found that social skills groups, the Picture Exchange Communication System, joint attention interventions, and parent-mediated strategies can improve social participation. The findings were less conclusive for interventions to improve play and leisure performance and to decrease restricted and repetitive behaviors, but several strategies showed promise with moderately strong supporting evidence. Occupational therapists should be guided by evidence when considering interventions to improve social participation, play, leisure, and restricted and repetitive behaviors in people with ASD. Additional research using more robust scientific methods is needed for many of the currently available strategies. PMID- 26356655 TI - Effectiveness of Ayres Sensory Integration(r) and Sensory-Based Interventions for People With Autism Spectrum Disorder: A Systematic Review. AB - This systematic review examines the literature published from January 2006 through April 2013 related to the effectiveness of Ayres Sensory Integration(r) (ASI) and sensory-based interventions (SBIs) within the scope of occupational therapy for people with autism spectrum disorder to improve performance in daily life activities and occupations. Of the 368 abstracts screened, 23 met the inclusion criteria and were reviewed. Moderate evidence was found to support the use of ASI. The results for sensory-based methods were mixed. Recommendations include performing higher level studies with larger samples, using the Fidelity Measure in studies of ASI, and using carefully operationalized definitions and systematic methods in examination of SBIs. PMID- 26356654 TI - Effectiveness of Work, Activities of Daily Living, Education, and Sleep Interventions for People With Autism Spectrum Disorder: A Systematic Review. AB - OBJECTIVE: To examine interventions addressing work, activities of daily living (ADLs), instrumental activities of daily living (IADLs), education, and sleep for people with autism spectrum disorder. METHOD: A total of 23 studies were identified, and 9 work-, 11 ADL/IADL-, and 3 education-related interventions were examined. No sleep studies were identified. RESULTS: Use of mobile and tablet technologies for vocational skills was supported. Support for ADL/IADL intervention is variable, with indications that Cognitive Orientation to Occupational Performance, sensory integration, and contextual interventions may increase occupational performance. Preliminary evidence suggests that daily yoga and brief exercise may improve classroom performance and behavior; group physical activities may assist with school readiness variables. Evidence for using technologies for IADLs was limited, as was evidence determining effective interventions for feeding and eating issues. CONCLUSIONS: Studies investigating interventions related to sleep are lacking. More studies are needed in all areas, presenting opportunities for the expansion of science-driven occupational therapy practice and research for people with ASD. PMID- 26356656 TI - Effectiveness of Interventions for Children With Autism Spectrum Disorder and Their Parents: A Systematic Review of Family Outcomes. AB - This systematic review examined the literature published from January 2006 to April 2013 related to the effectiveness of occupational therapy interventions for children with autism spectrum disorder (ASD) and their parents to improve parental stress and self-efficacy, coping, and resilience and family participation in daily life and routines. From the 4,457 abstracts, 34 articles were selected that matched the inclusion criteria. The results were mixed and somewhat inconclusive because this body of literature is in its infancy. Studies of children with ASD do not routinely measure parental and family outcomes. Recommendations include an emphasis on family measures other than parental stress and a greater focus on measures of parental and family functioning in all future studies of pediatric interventions to more fully understand the impact of interventions in a wider context. PMID- 26356657 TI - Linking Sensory Factors to Participation: Establishing Intervention Goals With Parents for Children With Autism Spectrum Disorder. AB - Parents often focus on independence in activities of daily living and social participation when setting goals for their children with autism spectrum disorders. Occupational therapy practitioners use clinical reasoning to translate these goals to define occupation-based outcomes. This article describes an exploratory analysis of 160 parent-identified goals for children with autism. We identified sensory integrative factors hypothesized to influence each goal and then categorized the goals using the Occupational Therapy Practice Framework: Domain and Process and the International Classification of Functioning, Disability and Health (ICF). Most goals were at the ICF participation and activity levels. Activities of daily living were the most common area of occupation identified, followed by social participation and play. Sensory reactivity and somatopraxis were the most frequently occurring sensory integrative factors. The value of addressing parent goals using a systematic reasoning process to identify factors affecting participation and the importance of measuring participation outcomes are discussed. PMID- 26356658 TI - Caregiving Experiences of Latino Families With Children With Autism Spectrum Disorder. AB - OBJECTIVE: Prior research has documented caregiving difficulties in families of children with autism spectrum disorder (ASD). However, Latino families may encounter unique challenges. The purpose of this study was to understand the caregiving experiences of Latino families with children with ASD, including daily activities, coping strategies, and service utilization. METHOD: Fifteen Latino parents of children with ASD were interviewed. The interviews were transcribed for analysis to identify themes of experiences unique to this population. RESULTS: Latino families of children with ASD encounter many similar issues as non-Latino families but also unique issues that affect service utilization. Four themes were identified: dealing with the diagnosis, dealing with stigma and isolation from family and community, understanding the role of mothers in changing family routines, and utilizing services. CONCLUSION: To meet the unique needs of Latino families, services need to be provided in culturally sensitive context that address children's needs within family units. PMID- 26356659 TI - Resilience in Daily Occupations of Indonesian Mothers of Children With Autism Spectrum Disorder. AB - This qualitative study investigated how resilience functions in the context of daily occupations for mothers of children with autism spectrum disorder (ASD). Fourteen mothers of children with ASD participated in two focus groups that were used to elicit stories of the mothers' resilience in daily occupations. A constant comparative method was used for data analysis. A model of resilience in daily occupations of mothers of children with ASD was developed consisting of four categories: (1) creating and re-creating accepting conditions, (2) finding solutions, (3) striving for balance among daily occupations, and (4) thinking about the child's future. Sources of resilience were found to reside in both the mothers themselves and their social environments. Occupational therapy practitioners can use these findings in developing supportive approaches aimed at mothers, family members, and other people in the lives of children with ASD. PMID- 26356660 TI - Content Analysis of Qualitative Research on Children and Youth With Autism, 1993 2011: Considerations for Occupational Therapy Services. AB - OBJECTIVE: Through a content analysis of qualitative research published 1993 2011, we sought to determine how qualitative research can inform clinical reasoning among occupational therapy practitioners to support evidence-based, occupation-focused services for children and youth with autism and their families. METHOD: A qualitative literature search of journals inside and outside occupational therapy, including international journals, yielded 125 articles. We reviewed 110 articles that met inclusion criteria, 79 of which were coded by four occupational therapists with experience working with families with a child or youth with autism. RESULTS: Nineteen content codes were initially derived. Three themes were identified: (1) service challenges for the family, (2) day-to-day experience of autism, and (3) reframing family. CONCLUSION: This content analysis illustrates how qualitative research may help occupational therapy practitioners make comprehensive, occupation-based intervention decisions by considering the lived experience of children and youth with autism and their families. PMID- 26356661 TI - Sensory Pattern Contributions to Developmental Performance in Children With Autism Spectrum Disorder. AB - Sensory processing differences in preschool-age children with autism spectrum disorder (ASD) affect their engagement in everyday activities, thereby influencing opportunities to practice and develop skills such as social communication and adaptive behavior. The purpose of this study was to investigate the extent to which specific sensory processing patterns relate to aspects of development (i.e., adaptive behavior, expressive and receptive language, fine and gross motor skills, social behavior) in a sample of preschool-age children with ASD (N=400). A retrospective chart review was used to gather clinical data. Results suggest that sensory processing patterns differentially affect children's developmental skills and adaptive behavior. Certain sensory processing patterns predicted children's development of language, motor, and adaptive skills. These findings have clear implications for occupational therapy practice with young children with ASD. Practitioners should consider how sensory processing in ASD both supports and limits children's ability to engage in social communication and learning opportunities. PMID- 26356662 TI - Developmental Dyspraxia and the Play Skills of Children With Autism. AB - OBJECTIVE: This study sought to investigate the impact of developmental dyspraxia on the play skills of children with autism spectrum disorder (ASD). METHOD: The praxis abilities of 32 children with ASD (mean age=7.5 yr) were assessed using two subtests of the Sensory Integration and Praxis Tests and the Planning and Ideas domain of the Sensory Processing Measure Home Form. Play and leisure skills were measured with the Vineland Adaptive Behavior Scales, Second Edition. Utilizing correlation coefficients, we investigated the relationship between developmental dyspraxia and the play skills of children with ASD. RESULTS: Children with ASD demonstrated definite dysfunction in imitative praxis abilities, the generation of ideas, and participation in age-appropriate play and leisure activities. CONCLUSION: Praxis problems in children with ASD greatly affect their successful participation in play and leisure activities. PMID- 26356663 TI - Retrospective Analysis of Motor Development in Infants at High and Low Risk for Autism Spectrum Disorder. AB - OBJECTIVE: To measure upper-extremity and gross motor skill development in infants with and without risk factors for autism spectrum disorder (ASD). METHOD: Data were coded retrospectively from 39 infants who participated in longitudinal structured early developmental assessments. Twenty-five infants were at high risk for ASD, and the remaining 14 infants were classified as low risk. Upper extremity and motor skill development were coded at ages 2, 4, and 6 mo. Five infants went on to receive an ASD diagnosis at age 2-4 yr. RESULTS: Infants at high risk for ASD demonstrated fewer midline behaviors with the upper extremities and delayed motor skill development than the low-risk group. Differences in motor skills were most apparent at age 4 mo. CONCLUSION: Early monitoring for motor delay in infants at high risk for ASD is warranted. Midline control and play with the upper extremities and overall motor skill development are possible assessment and therapeutic targets. PMID- 26356664 TI - In-Home Occupational Performance Evaluation for Providing Assistance (I-HOPE Assist): An Assessment for Informal Caregivers. AB - Home modification interventions have the potential to provide support to informal caregivers; however, the impact of these interventions on caregivers is understudied, and adequate assessments are lacking. This study describes the development and preliminary psychometric properties of a performance-based assessment that identifies environmental barriers to performance of daily caregiving activities. An existing assessment of person-environment fit was modified using key informant interviews and was administered to 31 informal caregivers. The In-Home Occupational Performance Evaluation for Providing Assistance demonstrated reliability across raters, good internal consistency for all subscales, and convergent validity with existing measures. This assessment has the potential to guide home modification interventions and measure the impact on informal caregiving in the home. PMID- 26356665 TI - Activity Pacing Self-Management in Chronic Fatigue Syndrome: A Randomized Controlled Trial. AB - OBJECTIVE: To evaluate the effectiveness of an activity pacing self-management (APSM) intervention in improving performance of daily life activities in women with chronic fatigue syndrome (CFS). METHOD: A total of 33 women with CFS (age 41.1+/-11.2 yr) were randomly allocated to APSM (experimental group; n=16) or relaxation (control group; n=17). Main outcome measures included the Canadian Occupational Performance Measure (COPM; primary) and Checklist Individual Strength (CIS). RESULTS: COPM scores changed significantly over time in both groups (p=.03). The change in Satisfaction scores showed a significant difference in favor only of APSM (effect size=0.74 [0.11, 1.4]). CIS scores decreased significantly in the experimental group only (p<.01). CONCLUSION: APSM was found to be feasible and effective in optimizing participation in desired daily life activities in women with CFS. Replication in a larger sample with long-term follow-up is required. PMID- 26356666 TI - Autonomy and Housing Accessibility Among Powered Mobility Device Users. AB - OBJECTIVE: To describe environmental barriers, accessibility problems, and powered mobility device (PMD) users' autonomy indoors and outdoors; to determine the home environmental barriers that generated the most housing accessibility problems indoors, at entrances, and in the close exterior surroundings; and to examine personal factors and environmental components and their association with indoor and outdoor autonomy. METHOD: This cross-sectional study was based on data collected from a sample of 48 PMD users with a spinal cord injury (SCI) using the Impact of Participation and Autonomy and the Housing Enabler instruments. Descriptive statistics and logistic regression were used. RESULTS: More years living with SCI predicted less restriction in autonomy indoors, whereas more functional limitations and accessibility problems related to entrance doors predicted more restriction in autonomy outdoors. CONCLUSION: To enable optimized PMD use, practitioners must pay attention to the relationship between client autonomy and housing accessibility problems. PMID- 26356667 TI - Contribution of Qualitative Research to Evidence in Practice for People With Autism Spectrum Disorder. AB - Appraising the best available evidence substantiating and informing occupational therapy practice is a commonly expressed obligation for the profession (American Occupational Therapy Association [AOTA], 2007). In this article we argue for the full inclusion of qualitative research, on parity with quantitative research, as a source for evidence of relevant and effective occupational therapy practice, review the limitations of quantitative research, and outline the distinctive contributions of qualitative studies to the practice of occupational therapy for people with autism spectrum disorder (ASD). In addition, we describe the role of qualitative studies in the fulfillment of the Centennial Vision (AOTA, 2007) and recommend three action steps for the profession. PMID- 26356668 TI - Occupational Therapy Interventions for Adults With Stroke. AB - Evidence Connection articles provide a clinical application of systematic reviews developed in conjunction with the American Occupational Therapy Association's (AOTA's) Evidence-Based Practice project. The clinical condition discussed in this inaugural Evidence Connection article is adults with stroke. Findings from the systematic reviews on this topic were published in the January/February 2015 issue of the American Journal of Occupational Therapy and in AOTA's Occupational Therapy Practice Guidelines for Adults With Stroke (Wolf & Nilsen, 2015). Each article in this series will summarize the evidence from the published reviews on a given topic and presents an application of the evidence to a related clinical case. Evidence Connection articles illustrate how the research evidence from the reviews can be used to inform and guide clinical decision making. PMID- 26356670 TI - By inhibiting Ras/Raf/ERK and MMP-9, knockdown of EpCAM inhibits breast cancer cell growth and metastasis. AB - Epithelial cell adhesion molecule (EpCAM) is a type I transmembrane protein that is expressed in the majority of normal epithelial tissues and is overexpressed in most epithelial cancers including breast cancer, where it plays an important role in cancer progression. However, the mechanism by which EpCAM promotes the progression of breast cancer is not understood. In this study, we found that EpCAM expression was increased in tumor tissue from breast cancer patients compared to healthy patients. Overexpression of EpCAM in breast cancer cells enhanced tumor cell growth in vitro and increased invasiveness, whereas small interfering RNA-mediated silencing of EpCAM (si-EpCAM) had the opposite effect. EpCAM knockdown led to decreased phosphorylation of Raf and ERK, suppression of malignant behavior of breast cancer cells, and inhibition of the Ras/Raf/ERK signaling pathway. Furthermore, si-EpCAM-mediated invasion and metastasis of breast carcinoma cells required the downregulation of matrix metalloproteinase-9 (MMP-9) through inhibition of this signaling pathway. In conclusion, our data show that knockdown of EpCAM can inhibition breast cancer cell growth and metastasis via inhibition of the Ras/Raf/ERK signaling pathway and MMP-9. PMID- 26356671 TI - Disulfiram anti-cancer efficacy without copper overload is enhanced by extracellular H2O2 generation: antagonism by tetrathiomolybdate. AB - HIGHLIGHTS: BACKGROUND: Cu/Zn superoxide dismutases (SODs) like the extracellular SOD3 and cytoplasmic SOD1 regulate cell proliferation by generating hydrogen peroxide (H2O2). This pro-oxidant inactivates essential cysteine residues in protein tyrosine phosphatases (PTP) helping receptor tyrosine kinase activation by growth factor signaling, and further promoting downstream MEK/ERK linked cell proliferation. Disulfiram (DSF), currently in clinical cancer trials is activated by copper chelation, being potentially capable of diminishing the copper dependent activation of MEK1/2 and SOD1/SOD3 and promoting reactive oxygen species (ROS) toxicity. However, copper (Cu) overload may occur when co administered with DSF, resulting in toxicity and mutagenicity against normal tissue, through generation of the hydroxyl radical (*OH) by the Fenton reaction. PURPOSE: To investigate: a) whether sub-toxic DSF efficacy can be increased without Cu overload against human melanoma cells with unequal BRAF(V600E) mutant status and Her2-overexpressing SKBR3 breast cancer cells, by increasing H2O2 from exogenous SOD; b) to compare the anti-tumor efficacy of DSF with that of another clinically used copper chelator, tetrathiomolybdate (TTM). RESULTS: a) without copper supplementation, exogenous SOD potentiated sub-toxic DSF toxicity antagonized by sub-toxic TTM or by the anti-oxidant N-acetylcysteine; b) exogenous glucose oxidase, another H2O2 generator resembled exogenous SOD in potentiating sub-toxic DSF. CONCLUSIONS: potentiation of sub-lethal DSF toxicity by extracellular H2O2 against the human tumor cell lines investigated, only requires basal Cu and increased ROS production, being unrelated to non-specific or TTM copper chelator sequestration. SIGNIFICANCE: These findings emphasize the relevance of extracellular H2O2 as a novel mechanism to improve disulfiram anticancer effects minimizing copper toxicity. PMID- 26356672 TI - Role of the short isoform of the progesterone receptor in breast cancer cell invasiveness at estrogen and progesterone levels in the pre- and post-menopausal ranges. AB - Overexpression of the progesterone receptor (PR) isoform A (PR-A) is a negative prognosticator for estrogen receptor (ER)-positive breast cancer but in vitro studies have implicated PR-B in progestin-induced invasiveness. As estrogen is known to suppress invasiveness and tumor progression and as the in vitro studies were conducted in models that either lacked ER or excluded estrogen, we examined the role of PR isoforms in the context of estrogen signaling. Estrogen (< 0.01nM) strongly suppressed invasiveness in various ER+ model cell lines. At low (< 1nM) concentrations, progestins completely abrogated inhibition of invasiveness by estrogen. It was only in a higher (5 nM - 50 nM) concentration range that progestins induced invasiveness in the absence of estrogen. The ability of low dose progestins to rescue invasiveness from estrogen regulation was exclusively mediated by PR-A, whereas PR-B mediated the estrogen-independent component of progestin-induced invasiveness. Overexpression of PR-A lowered the progestin concentration needed to completely rescue invasiveness. Among estrogen-regulated genes, progestin/PR-A counter-regulated a distinctive subset, including breast tumor progression genes (e.g., HES1, PRKCH, ELF5, TM4SF1), leading to invasiveness. In this manner, at relatively low hormone concentrations (corresponding to follicular stage and post-menopausal breast tissue or plasma levels), progesterone influences breast cancer cell invasiveness by rescuing it from estrogen regulation via PR-A, whereas at higher concentrations the hormone also induces invasiveness independent of estrogen signaling, through PR-B. The findings point to a direct functional link between PR-A and progression of luminal breast cancer in the context of the entire range of pre- and post menopausal plasma and breast tissue hormone levels. PMID- 26356673 TI - Aberrant reduction of telomere repetitive sequences in plasma cell-free DNA for early breast cancer detection. AB - Excessive telomere shortening is observed in breast cancer lesions when compared to adjacent non-cancerous tissues, suggesting that telomere length may represent a key biomarker for early cancer detection. Because tumor-derived, cell-free DNA (cfDNA) is often released from cancer cells and circulates in the bloodstream, we hypothesized that breast cancer development is associated with changes in the amount of telomeric cfDNA that can be detected in the plasma. To test this hypothesis, we devised a novel, highly sensitive and specific quantitative PCR (qPCR) assay, termed telomeric cfDNA qPCR, to quantify plasma telomeric cfDNA levels. Indeed, the internal reference primers of our design correctly reflected input cfDNA amount (R(2) = 0.910, P = 7.82 * 10(-52)), implying accuracy of this assay. We found that plasma telomeric cfDNA levels decreased with age in healthy individuals (n = 42, R(2) = 0.094, P = 0.048), suggesting that cfDNA is likely derived from somatic cells in which telomere length shortens with increasing age. Our results also showed a significant decrease in telomeric cfDNA level from breast cancer patients with no prior treatment (n = 47), compared to control individuals (n = 42) (P = 4.06 * 10(-8)). The sensitivity and specificity for the telomeric cfDNA qPCR assay was 91.49% and 76.19%, respectively. Furthermore, the telomeric cfDNA level distinguished even the Ductal Carcinoma In Situ (DCIS) group (n = 7) from the healthy group (n = 42) (P = 1.51 * 10(-3)). Taken together, decreasing plasma telomeric cfDNA levels could be an informative genetic biomarker for early breast cancer detection. PMID- 26356675 TI - Sucrose-Formulated Recombinant Factor VIII Dosing Flexibility in Prophylaxis Regimens: Experience from Postmarketing Surveillance Studies. AB - Objectives. Prophylaxis regimens for severe hemophilia A allowing more flexible dosing while maintaining efficacy may improve adherence and decrease the cost of prophylaxis. Here, we compared the clinical effectiveness of once- or twice weekly versus >=3-times-weekly prophylaxis with sucrose-formulated recombinant factor VIII (rFVIII-FS) in a "real-world" practice setting. Methods. Data from 3 postmarketing studies were pooled. Patients with severe hemophilia A receiving >=1 prophylaxis infusion/wk of rFVIII-FS for >=80% of a prophylaxis observation period (>=5 months) were included. Patients were categorized based on physician assigned treatment regimens of 1-2 prophylaxis injections/wk (n = 63) or >=3 prophylaxis injections/wk (n = 76). Descriptive statistics were determined for annualized bleeding rates (ABRs). Results. Median (quartile 1; quartile 3) ABR for all bleeds was 2.0 (0; 4.0) in the 1-2 prophylaxis injections/wk group and 3.9 (1.5; 9.3) in the >=3 prophylaxis injections/wk group. Median ABRs for joint, spontaneous, and trauma-related bleeds were numerically lower with 1-2 prophylaxis injections/wk. As an estimate of prophylaxis success, 63% (>=3 prophylaxis injections/wk) to 84% of patients (1-2 prophylaxis injections/wk) had <=4 annualized joint bleeds. Conclusions. Dosing flexibility and successful prophylaxis with rFVIII-FS were demonstrated. Very good bleeding control was achieved with both once-twice-weekly and >=3-times-weekly prophylaxis dosing regimens. PMID- 26356674 TI - The search for cis-regulatory driver mutations in cancer genomes. AB - With the advent of high-throughput and relatively inexpensive whole-genome sequencing technology, the focus of cancer research has begun to shift toward analyses of somatic mutations in non-coding cis-regulatory elements of the cancer genome. Cis-regulatory elements play an important role in gene regulation, with mutations in these elements potentially resulting in changes to the expression of linked genes. The recent discoveries of recurrent TERT promoter mutations in melanoma, and recurrent mutations that create a super-enhancer regulating TAL1 expression in T-cell acute lymphoblastic leukaemia (T-ALL), have sparked significant interest in the search for other somatic cis-regulatory mutations driving cancer development. In this review, we look more closely at the TERT promoter and TAL1 enhancer alterations and use these examples to ask whether other cis-regulatory mutations may play a role in cancer susceptibility. In doing so, we make observations from the data emerging from recent research in this field, and describe the experimental and analytical approaches which could be adopted in the hope of better uncovering the true functional significance of somatic cis-regulatory mutations in cancer. PMID- 26356676 TI - Use of a three-dimensional humanized liver model for the study of viral gene vectors. AB - Reconstituted three-dimensional (3D) liver models obtained by engrafting hepatic cells into an extracellular matrix (ECM) are valuable tools to study tissue regeneration, drug action and toxicology ex vivo. The aim of the present study was to establish a system for the functional investigation of a viral vector in a 3D liver model composed of human HepG2 cells on a rat ECM. An adeno-associated viral (AAV) vector expressing the Emerald green fluorescent protein (EmGFP) and a short hairpin RNA (shRNA) directed against human cyclophilin b (hCycB) was injected into the portal vein of 3D liver models. Application of the vector did not exert toxic effects, as shown by analysis of metabolic parameters. Six days after transduction, fluorescence microscopy analysis of EmGFP production revealed widespread distribution of the AAV vectors. After optimization of the recellularization and transduction conditions, averages of 55 and 90 internalized vector genomes per cell in two replicates of the liver model were achieved, as determined by quantitative PCR analysis. Functionality of the AAV vector was confirmed by efficient shRNA-mediated knockdown of hCycB by 70-90%. Our study provides a proof-of-concept that a recellularized biological ECM provides a valuable model to study viral vectors ex vivo. PMID- 26356677 TI - Toward a Deuterium Feather Isoscape for Sub-Saharan Africa: Progress, Challenges and the Path Ahead. AB - A key challenge to the application of continent-wide feather isoscapes for geographic assignment of migrant birds is the lack of ground-truthed samples. This is especially true for long-distance Palearctic-Afrotropical migrants. We used spatially-explicit information on the delta2H composition of archived feathers from Green-backed/Grey-backed Camaroptera, to create a feather delta2H isoscape for sub-Saharan Africa. We sampled from 34 out of 41 sub-Saharan countries, totaling 205 sampling localities. Feather samples were obtained from museum collections (n = 224, from 1950 to 2014) for delta2H assay. Region, altitude, annual rainfall and seasonal patterns in precipitation were revealed as relevant explanatory variables for spatial patterns in feather delta2H. Predicted feather delta2H values ranged from -4.0 0/00 to -63.3 0/00, with higher values observed in the Great Rift Valley and South Africa, and lower values in central Africa. Our feather isoscape differed from that modelled previously using a precipitation delta2H isoscape and an assumed feather-to-precipitation calibration, but the relatively low model goodness fit (F10,213 = 5.98, p<0.001, R2 = 0.18) suggests that other, non-controlled variables might be driving observed geographic patterns in feather delta2H values. Additional ground truthing studies are therefore recommended to improve the accuracy of the African feather delta2H isoscape. PMID- 26356678 TI - Development of a high affinity Affibody-derived protein against amyloid beta peptide for future Alzheimer's disease therapy. PMID- 26356679 TI - In Vitro Ion Chelating, Antioxidative Mechanism of Extracts from Fruits and Barks of Tetrapleura tetraptera and Their Protective Effects against Fenton Mediated Toxicity of Metal Ions on Liver Homogenates. AB - The aim of the present study was to investigate the antioxidant activity and protective potential of T. tetraptera extracts against ion toxicity. The antioxidant activity of the extracts was investigated spectrophotometrically against several radicals (1,1-diphenyl-2-picrylhydrazyl (DPPH(*)), 2,2'-azino bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS(*)), hydroxyl radical (HO(*)), and nitric oxide (NO(*))), followed by the ferric reducing power, total phenols, flavonoid, and flavonol contents. The effects of the extracts on catalase (CAT), superoxide dismutase (SOD), and peroxidase activities were also determined using the standard methods as well as the polyphenol profile using HPLC. The results showed that the hydroethanolic extract of T. tetraptera (CFH) has the lowest IC50 value with the DPPH, ABTS, OH, and NO radicals. The same extract also exhibited the significantly higher level of total phenols (37.24 +/- 2.00 CAE/g dried extract); flavonoids (11.36 +/- 1.88 QE/g dried extract); and flavonols contents (3.95 +/- 0.39 QE/g dried extract). The HPLC profile of T. tetraptera revealed that eugenol (958.81 +/- 00 mg/g DW), quercetin (353.78 +/- 00 mg/g DW), and rutin (210.54 +/- 00 mg/g DW) were higher in the fruit than the bark extracts. In conclusion, extracts from T. tetraptera may act as a protector against oxidative mediated ion toxicity. PMID- 26356680 TI - A Highly Stereoselective and Scalable Synthesis of L-allo-Enduracididine. AB - A highly stereoselective and scalable synthesis of L-allo-enduracididine from hydroxyproline derivative is described. Pyrrolidine oxidation and reductive ring opening are the key steps in the synthesis. Compared to previously reported approaches, the current route affords l-allo-enduracididine in 10 steps from 3 in 31% overall yield with >50:1 diastereoselectivity. PMID- 26356681 TI - Effects of host plant on life-history traits in the polyphagous spider mite Tetranychus urticae. AB - Studying antagonistic coevolution between host plants and herbivores is particularly relevant for polyphagous species that can experience a great diversity of host plants with a large range of defenses. Here, we performed experimental evolution with the polyphagous spider mite Tetranychus urticae to detect how mites can exploit host plants. We thus compared on a same host the performance of replicated populations from an ancestral one reared for hundreds of generations on cucumber plants that were shifted to either tomato or cucumber plants. We controlled for maternal effects by rearing females from all replicated populations on either tomato or cucumber leaves, crossing this factor with the host plant in a factorial design. About 24 generations after the host shift and for all individual mites, we measured the following fitness components on tomato leaf fragments: survival at all stages, acceptance of the host plant by juvenile and adult mites, longevity, and female fecundity. The host plant on which mite populations had evolved did not affect the performance of the mites, but only affected their sex ratio. Females that lived on tomato plants for circa 24 generations produced a higher proportion of daughters than did females that lived on cucumber plants. In contrast, maternal effects influenced juvenile survival, acceptance of the host plant by adult mites and female fecundity. Independently of the host plant species on which their population had evolved, females reared on the tomato maternal environment produced offspring that survived better on tomato as juveniles, but accepted less this host plant as adults and had a lower fecundity than did females reared on the cucumber maternal environment. We also found that temporal blocks affected mite dispersal and both female longevity and fecundity. Taken together, our results show that the host plant species can affect critical parameters of population dynamics, and most importantly that maternal and environmental conditions can facilitate colonization and exploitation of a novel host in the polyphagous T. urticae, by affecting dispersal behavior (host acceptance) and female fecundity. PMID- 26356682 TI - Developmental evaluation of atypical auditory sampling in dyslexia: Functional and structural evidence. AB - Whether phonological deficits in developmental dyslexia are associated with impaired neural sampling of auditory information at either syllabic- or phonemic rates is still under debate. In addition, whereas neuroanatomical alterations in auditory regions have been documented in dyslexic readers, whether and how these structural anomalies are linked to auditory sampling and reading deficits remains poorly understood. In this study, we measured auditory neural synchronization at different frequencies corresponding to relevant phonological spectral components of speech in children and adults with and without dyslexia, using magnetoencephalography. Furthermore, structural MRI was used to estimate cortical thickness of the auditory cortex of participants. Dyslexics showed atypical brain synchronization at both syllabic (slow) and phonemic (fast) rates. Interestingly, while a left hemispheric asymmetry in cortical thickness was functionally related to a stronger left hemispheric lateralization of neural synchronization to stimuli presented at the phonemic rate in skilled readers, the same anatomical index in dyslexics was related to a stronger right hemispheric dominance for neural synchronization to syllabic-rate auditory stimuli. These data suggest that the acoustic sampling deficit in development dyslexia might be linked to an atypical specialization of the auditory cortex to both low and high frequency amplitude modulations. PMID- 26356683 TI - Experimental and Theoretical Study of the Kinetics of the OH + Propionaldehyde Reaction between 277 and 375 K at Low Pressure. AB - Measurements of the rate constant for the reaction of OH radicals with propionaldehyde as a function of temperature were performed using low-pressure discharge-flow tube techniques coupled with laser-induced fluorescence detection of OH radicals. The measured room-temperature rate constant of (1.51 +/- 0.22) * 10(-11) cm(3) molecules(-1) s(-1) at 4 Torr was generally lower but in reasonable agreement with previous absolute and relative rate studies at higher pressures. Measurements as a function of temperature resulted in an Arrhenius expression of (2.3 +/- 0.4) * 10(-11) exp[(-110 +/- 50)/T] cm(3) molecules(-1) s(-1) between 277 and 375 K at 4 Torr. The observed temperature dependence at low pressure is in contrast to previous measurements of a negative temperature dependence at higher pressures. Ab initio calculations of the potential energy surface for this reaction suggest that the primary reaction pathway involves the formation of a hydrogen-bonded prereactive complex, which could account for the difference in the observed temperature dependence at lower and higher pressures. PMID- 26356684 TI - Outward Rectification of Voltage-Gated K+ Channels Evolved at Least Twice in Life History. AB - Voltage-gated potassium (K+) channels are present in all living systems. Despite high structural similarities in the transmembrane domains (TMD), this K+ channel type segregates into at least two main functional categories-hyperpolarization activated, inward-rectifying (Kin) and depolarization-activated, outward rectifying (Kout) channels. Voltage-gated K+ channels sense the membrane voltage via a voltage-sensing domain that is connected to the conduction pathway of the channel. It has been shown that the voltage-sensing mechanism is the same in Kin and Kout channels, but its performance results in opposite pore conformations. It is not known how the different coupling of voltage-sensor and pore is implemented. Here, we studied sequence and structural data of voltage-gated K+ channels from animals and plants with emphasis on the property of opposite rectification. We identified structural hotspots that alone allow already the distinction between Kin and Kout channels. Among them is a loop between TMD S5 and the pore that is very short in animal Kout, longer in plant and animal Kin and the longest in plant Kout channels. In combination with further structural and phylogenetic analyses this finding suggests that outward-rectification evolved twice and independently in the animal and plant kingdom. PMID- 26356685 TI - Preoperative Proton Beam Therapy for Thymoma: A Case Report. AB - We performed preoperative proton beam therapy for locally advanced thymoma and subsequently achieved complete resection. The patient was 31-year old woman, in whom chest computed tomography revealed a huge mass at the left anterior mediastinum. We diagnosed locally advanced type B3 thymoma. Because of the potential for complications to the lung and heart, definitive photon radiation therapy would have been difficult to administer. Therefore, we performed proton beam therapy, which could be administered within dose limitations. After proton beam therapy, the huge tumor had remarkably decreased in size. We were thereby able to achieve complete resection. As of 24 months after surgery, the patient has not developed any severe adverse events associated with proton beam therapy. Our experience suggests that preoperative proton beam therapy may be an effective modality for reducing tumor size, facilitating complete resection, and preventing toxicity of radiation therapy. PMID- 26356686 TI - Multidisciplinary Treatment Approach for Prosthetic Vascular Graft Infection in the Thoracic Aortic Area. AB - Prosthetic vascular graft infection in the thoracic aortic area is a rare but serious complication. Adequate management of the complication is essential to increase the chance of success of open surgery. While surgical site infection is suggested as the root cause of the complication, it is also related to decreased host tolerance, especially as found in elderly patients. The handling of prosthetic vascular graft infection has been widely discussed to date. This paper mainly provides a summary of literature reports published within the past 5 years to discuss issues related to multidisciplinary treatment approaches, including surgical site infection, timing of onset, diagnostic methods, causative pathogens, auxiliary diagnostic methods, antibiotic treatment, anti-infective structures of vascular prostheses, surgical treatment, treatment strategy against infectious aortic aneurysms, future surgical treatment, postoperative systemic therapy, and antimicrobial stewardship. A thorough understanding of these issues will enable us to prevent prosthetic vascular graft infection in the thoracic aortic area as far as possible. In the event of its occurrence, the early introduction of appropriate treatment is expected to cure the disease without worsening of the underlying pathological condition. PMID- 26356687 TI - Replication and Meta-Analysis of Common Gene Mutations in TTF1 and TTF2 with Papillary Thyroid Cancer. AB - Papillary thyroid cancer (PTC), one of the most common malignant thyroid tumors, exits widely in the thyroid of adolescents. Thyroid transcription factor 1 (TTF1) and 2 (TTF2) were thyroid-specific transcription factors, and regulated expression of the thyroid-specific genes. Hence, the aim of the present study was to evaluate the correlation between gene variants of TTF1 and TTF2 and the risk of PTC in Chinese population.Two tagging single-nucleotide polymorphisms (tSNPs) on TTF1 and TTF2 were selected and genotyped by matrix-assisted laser desorption/ionization time-of-flight (MALDITOF) mass spectrometry in a hospital based case-control study of 297 PTC patients and 594 healthy controls. Furthermore, a meta-analysis of the association between TTF1 and TTF2 and PTC risk was also performed.We found that the rs944289 on the TTF1 was significantly associated with increased PTC risk (TT vs CC, OR = 1.53, 95% CI = 1.05-2.24; CT + TT vs TT, OR = 1.34, 95% CI = 1.00-1.79; T vs C, OR = 1.27, 95% CI = 1.04-1.55). Similarly, the rs965513 on the TTF2 can also elevate the risk of PTC significantly (GA vs GG, OR = 1.67, 95% CI = 1.07-2.59; AA+GA vs AA, OR = 1.37, 95% CI = 1.09-1.82; A vs G, OR = 1.29, 95% CI = 1.05-1.59). Furthermore, results of stratified analysis revealed that the risk effects of rs944289 and rs965513 were more overpowering in the subgroups of patients with MNG, as well as subjects without metastasis. Results of meta-analysis from the previous study and our new data indicated that variants of rs944289 and rs965513 might be the genetic susceptible factors both in Asians and Caucasians.We get the conclusion that mutations of TTF1 and TTF2 are significantly associated with an increasing risk of PTC in Chinese. However, more detailed investigations and further large-scale studies on genetic functions to provide more conclusive and accurate evidence are required in the future. PMID- 26356688 TI - Clinical Features and Outcomes of Pasteurella multocida Infection. AB - Pasteurella multocida, a zoonotic infectious organism, has most often been described in patients after an animal bite. Here, we characterize the clinical features and outcomes of P multocida infection in a large cohort of patients according to the presence or absence of an animal bite.We retrospectively searched MUSC's laboratory information system for all patients with positive P multocida cultures from 2000 to 2014. Extensive data were abstracted, including clinical and outcome data. The Charlson comorbidity index (CCI) was used to assess comorbidities among patients.We identified 44 patients with P multocida infections, including 25 with an animal bite. The average age was 64 years and the majority of patients were women (N = 30). There was no difference in age and sex distribution among those with and without a bite (P = 0.38 and 0.75, respectively). A CCI >=1 was significantly associated with the absence of a bite (P = 0.006). Patients presenting without a bite were more frequently bacteremic (37% vs 4%, respectively, P = 0.001), and were hospitalized more often (84% vs 44%, respectively, P = 0.012). Of the 8 patients who required intensive care unit (ICU)-based care, 7 were non-bite-related. There were 4 deaths, all occurring in patients not bitten.P multocida infections not associated with an animal bite were often associated with bacteremia, severe comorbidity(ies), immune incompetent states, the need for ICU management, and were associated with substantial mortality. PMID- 26356689 TI - Enhanced Recovery After Surgery: Which Components, If Any, Impact on The Systemic Inflammatory Response Following Colorectal Surgery?: A Systematic Review. AB - Enhanced Recovery or Fast Track Recovery after Surgery protocols (ERAS) have significantly changed perioperative care following colorectal surgery and are promoted as reducing the stress response to surgery.The present systematic review aimed to examine the impact on the magnitude of the systemic inflammatory response (SIR) for each ERAS component following colorectal surgery using objective markers such as C-reactive protein (CRP) and interleukin-6 (IL-6).A literature search was performed of the US National Library of Medicine (MEDLINE), EMBASE, PubMed, and the Cochrane Database of Systematic Reviews using appropriate keywords and subject headings to February 2015.Included studies had to assess the impact of the selected ERAS component on the SIR using either CRP or IL 6.Nineteen studies, including 1898 patients, were included. Fourteen studies (1246 patients) examined the impact of laparoscopic surgery on the postoperative markers of SIR. Ten of these studies (1040 patients) reported that laparoscopic surgery reduced postoperative CRP. One study (53 patients) reported reduced postoperative CRP using opioid-minimising analgesia. One study (142 patients) reported no change in postoperative CRP following preoperative carbohydrate loading. Two studies (108 patients) reported conflicting results with respect to the impact of goal-directed fluid therapy on postoperative IL-6. No studies examined the effect of other ERAS components, including mechanical bowel preparation, antibiotic prophylaxis, thromboprophylaxis, and avoidance of nasogastric tubes and peritoneal drains on markers of the postoperative SIR following colorectal surgery.The present systematic review shows that, with the exception of laparoscopic surgery, objective evidence of the effect of individual components of ERAS protocols in reducing the stress response following colorectal surgery is limited. PMID- 26356690 TI - Acute Splenic Infarction at an Academic General Hospital Over 10 Years: Presentation, Etiology, and Outcome. AB - Few case series provide a current, comprehensive, and detailed description of splenic infarction (SI), an uncommon condition.Retrospective chart review complemented by imaging evaluation and patient follow-up.All adult patients with a confirmed diagnosis of acute SI discharged over 10 years from a single academic center were studied. A systematic literature review was done to compile a complete list of SI etiologies.SI was found in 32 patients, 0.016% of admissions. Ages ranged from 18 to 86 (median 64) years. Cardiogenic emboli were the predominant etiology (20/32, 62.5%) and atrial fibrillation was frequent. Other patients had autoimmune disease (12.5%), associated infection (12.5%), or hematological malignancy (6%). Nine of the patients (28%) had been previously healthy or with no recognized morbidity predisposing to SI. In 5 of 9 hitherto silent antiphospholipid syndrome or mitral valve disease had been identified. Two remained cryptogenic. Most patients presented with abdominal pain (84%), often felt in the left upper quadrant or epigastrium. Associated symptoms, leukocytosis or increased serum lactate dehydrogenase occurred inconsistently (~25% each). Chest X-ray showed suggestive Lt. supra-diaphragmatic findings in 22%. Thus, the typical predisposing factors and/or clinical presentation should suggest SI to the clinician and be followed by early imaging by computed tomography (CT), highly useful also in atypical presentations. Complications were rare and patients were discharged after 6.5 days (median) on anticoagulant treatment. The systematic literature review revealed an extensive list of conditions underlying SI. In some, SI may be the first and presenting manifestation.SI is a rare event but should be considered in predisposed patients or those with any combination of suggestive clinical features, especially abdominal pain CT evaluation is diagnostic and the outcome is good. PMID- 26356691 TI - Asthma and Risk of Prostate Cancer: A Population-Based Case-Cohort Study in Taiwan. AB - Several epidemiologic studies in Western countries have examined the association between asthma and prostate cancer risk, but the results have been inconclusive. We investigated this association in a large, nationwide, population-based case cohort study. Using the Taiwan National Health Insurance Research Database from 1997 to 2008, we collected data from 12,372 men, including 4124 with asthma and 8248 age-, residence-, and insurance premium-matched control subjects, who were never diagnosed with asthma. Competing risk-adjusted Cox proportional hazards regression was used to calculate the hazard ratios (HRs) and 95% confidence interval (CI) for determining the association between prostate cancer and asthma. During a mean follow-up of 5.05 years (standard deviation, 2.10), there were 74 cases of prostate cancer. The incidence of prostate cancer was 163.0/100,000 person-years (95% CI: 113.0-228.0) in the asthma patients. Asthma was significantly associated with prostate cancer (HR: 2.36; 95% CI: 1.22-4.57; P = 0.011) after adjusting for age, residential area, insurance premium, hypertriglyceridemia, hypertension, diabetes mellitus, chronic obstructive pulmonary disease, duration of hospitalization, and mortality. In the subgroup analysis, independent risk factors for prostate cancer among men with asthma were age (HR: 1.09; 95% CI: 1.05-1.21; P < 0.001) and hypertension (HR: 2.75; 95% CI: 1.24-7.80; P = 0.047). The results of our study suggest that men with asthma have an increased risk of prostate cancer. PMID- 26356692 TI - Overestimated Oncologic Significance of Lymph Node Metastasis in G1 Nonfunctioning Neuroendocrine Tumor in the Left Side of the Pancreas. AB - Recent studies have expounded on the oncologic significance of lymph node metastasis in nonfunctioning (NF) neuroendocrine tumors (NETs) of the pancreas and suggest regional lymph node dissection for treating pancreatic NET. We tested this recommendation in NF pancreatic NET-G1, as these tumors are generally small and suitable for function-preserving minimally invasive pancreatectomy.From January 2005 to December 2014, medical records of patients who underwent pancreatectomy for pathologically confirmed NF NET-G1 of the left side of the pancreas were retrospectively reviewed. Oncologic outcomes were compared between limited pancreatectomy and distal pancreatosplenectomy.Thirty-five patients (14 males and 21 females) with a mean age of 55.9 +/- 11.4 years were enrolled in this study. Six patients (17.1%) underwent distal pancreatosplenectomy. Limited pancreatectomies comprised 15 spleen-preserving distal pancreatectomies (42.8%), 10 enucleations (28.6%), and 4 central pancreatectomies (11.4%). Lymph node metastasis was not found in 6 patients who underwent distal pancreatectomy with a splenectomy; meanwhile, the others were regarded as pNx since no lymph node retrieval was attempted during the limited pancreatectomy. Overall disease-free survival was 36.5 months (95% confidence interval [CI]: 25.9-47.1) and no tumor related mortality was noted. Minimally invasive pancreatectomy (P = 0.557) and limited pancreatectomy (P = 0.758) showed no adverse impact in treating NF NET-G1 of the left side of the pancreas.The oncologic significance of lymph node metastasis is overestimated in NF NET-G1 of the left side of the pancreas. Routine conventional distal pancreatosplenectomy to retrieve regional lymph nodes may be too excessive in treating NF NET-G1 of the distal pancreas. PMID- 26356693 TI - The Evaluation of Daily Life Activities after Application of an Osseointegrated Prosthesis Fixation in a Bilateral Transfemoral Amputee: A Case Study. AB - Individuals with a transfemoral amputation (TFA) may experience limitations in daily life due to reduced mobility and prosthesis-related problems. An osseointegrated prosthesis fixation (OPF) procedure in amputees might contribute to a solution for patients with short stumps or socket-related problems. To date, no study has specifically described the application of an OPF procedure in individuals with a TFA. This study evaluated the level of daily life activities of a 21-year old service member with a bilateral TFA and cerebral trauma. Due to a short stump length and coordination problems, an OPF procedure was deemed the most suitable option.The result of this procedure and the rehabilitation program showed an increased mobility and satisfaction as obtained by the assessment of life habits questionnaire (LIFE-H) and lower extremity functional scale. The participant was able to walk short distances and the Genium knee provided a stance position. Stair ambulation is impossible because of inadequate muscle capacity.In this specific case we conclude that the quality of life improved through the use of an OPF. However, OPF might not be the appropriate device for every individual with TFA, due to varying bone compositions, co-morbidities, and limited clinical experience and unknown long-term effects. PMID- 26356694 TI - Metabolic Syndrome-Associated Risk Factors and High-Sensitivity C-Reactive Protein Independently Predict Arterial stiffness in 9903 Subjects With and Without Chronic Kidney Disease. AB - Metabolic syndrome (MS), high-sensitivity C-reactive protein (hs-CRP), and chronic kidney disease (CKD) are related to cardiovascular diseases. Although MS is common in CKD subjects, the contribution of MS-associated risk factors and hs CRP to arterial stiffness in CKD has not been well studied.In this cross sectional cohort study, we enrolled 9903 subjects who underwent brachial-ankle pulse wave velocity (baPWV) measurements from our database of Health Care Center. CKD was defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m. Comparing those grouped with and without CKD, multivariate linear regression analyses were used.Overall, baPWV was found to have an inverse relationship with eGFR (P for trend <0.001), which increased progressively with the presence of CKD, increasing number of MS-associated risk factors and hs-CRP (P for trend <0.001). In the non-CKD group, age, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting glucose, triglyceride, high-density lipoprotein cholesterol, and hs-CRP independently predicted baPWV, whereas in CKD, eGFR, age, gender, body mass index, SBP, DBP, and fasting glucose remained predictors.The number of MS-associated risk factors and hs-CRP remains a determinant of arterial stiffness in both CKD and non-CKD groups. The decline of renal function contributes to arterial stiffness only in CKD but not in non-CKD. Our findings suggest that for CKD subjects, renal function, BP, and glycemic control are potential targets for further interventional studies of arterial stiffness. PMID- 26356695 TI - Myocardial Noncompaction Presenting With Myocardial Bridge: A Case Report. AB - Myocardial noncompaction, namly isolated noncompaction of the left ventricular myocardium (NVM), is a rare congenital disease. It can be either seen in the absence of other cardiac anomalies, or associated with other congenital cardiac defects, mostly stenotic lesions of the left ventricular outflow tract. A myocardial bridge (MB) is thought being associated with coronary heart disease, such as coronary spasm, arrhythmia, and so on. The significance of MB in association with other congenital cardiac conditions is unknown.We report a novel case who was presented NVM and MB. A 34-year-old man complained of chest prickling-like pain and dizzy for 1 year. His blood pressure was 110/70 mm Hg. Echocardiograph revealed increased trabeculations below the level of papillary muscle of left ventricle (LV); deep intertrabecular recesses in the endocardial wall of LV particularly in apex free wall; and LV ejection fraction of 57%. A coronary computerized tomography scan showed that part, 38.9 cm, of left descending artery tunnel was surrounding by cardiac muscles rather than resting on top of the myocardium.The therapeutics interventions included lifestyle cares, agents of anti-ischemia and improvement myocardial cell metabolism. The patient was followed up for 2.6 years, and his general condition was stable.This case indicates that NVM can be developed with MB, and the complete diagnosis of NVM and MB should be made by different image studies. PMID- 26356696 TI - Prognostic and Clinicopathological Value of Survivin in Diffuse Large B-cell Lymphoma: A Meta-Analysis. AB - Up to date, survivin, a well-known inhibitor of apoptosis, has attracted considerable attention as a potential biomarker and therapeutic target in diffuse large B-cell lymphoma (DLBCL). Nevertheless, there still remains no consensus on heterogeneous results. Herein, a meta-analysis was performed to clarify a convincing significance of survivin status on prognosis and clinicopathology of DLBCL patients.Eligible studies were identified by searching Medline, Embase, Scopus, CNKI, and Wanfang databases (last updated on November 30, 2014). Pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Heterogeneity and sensitivity were also analyzed. Moreover, Begg, Egger test, and funnel plots were applied to evaluate the publication bias.We finally included 17 eligible studies with the total number of 1352 patients in the meta-analysis. The pooled results showed that positive survivin expression in DLBCL was associated with inferior overall survival (OS) (HR: 1.880, 95% CI: 1.550-2.270) in patients. Moreover, a significant association was revealed between survivin expression and advanced clinical stage (III + IV) (OR: 0.611, 95% CI: 0.452-0.827), higher International Prognosis Index (IPI) score (Score 3-5) (OR: 0.559; 95% CI: 0.410-0.761), elevated serum lactic dehydrogenase (LDH) (OR: 0.607, 95% CI: 0.444-0.831), presence of bone marrow involvement (OR: 2.127, 95% CI: 1.154-3.921) together with reduced complete remission (CR) rate (OR: 0.478, 95% CI: 0.345-0.662).The results suggest that survivin could be a useful prognostic biomarker, and a promising target for DLBCL therapeutic intervention. Considering limited HR data adjusted for standard prognostic variables could be retrieved, future high-quality studies will be needed in evaluating the independent prognostic value of survivin expression in DLBCL. PMID- 26356697 TI - Nodal Basin Recurrence After Sentinel Lymph Node Biopsy for Melanoma: A Retrospective Multicenter Study in 2653 Patients. AB - The objective of this study was to analyze different types of nodal basin recurrence after sentinel lymph node biopsy (SLNB) for melanoma. PATIENTS AND METHODS: Kaplan-Meier estimates and the Cox proportional hazards model were used to study 2653 patients from 3 German melanoma centers retrospectively.The estimated 5-year negative predictive value of SLNB was 96.4%. The estimated false negative (FN) rates after 1, 2, 3, 5, and 10 years were 2.5%, 4.6%, 6.4%, 8.7%, and 12.6%, respectively. Independent factors associated with false negativity were older age, fewer SLNs excised, and head or neck location of the primary tumor. Compared with SLN-positive patients, the FNs had a significantly lower survival. In SLN-positive patients undergoing completion lymphadenectomy (CLND), the 5-year nodal basin recurrence rate was 18.3%. The recurrence rates for axilla, groin, and neck were 17.2%, 15.5%, and 44.1%, respectively. Significant factors predicting local relapse after CLND were older age, head, or neck location of the primary tumor, ulceration, deeper penetration of the metastasis into the SLN, tumor-positive CLND, and >2 lymph node metastases. All kinds of nodal relapse were associated with a higher prevalence of in-transit metastases.The FN rate after SLNB steadily increases over the observation period and should, therefore, be estimated by the Kaplan-Meier method. False-negativity is associated with fewer SLNs excised. The beneficial effect of CLND on nodal basin disease control varies considerably across different risk groups. This should be kept in mind about SLN-positive patients when individual decisions on prophylactic CLND are taken. PMID- 26356698 TI - The Effect of Exercise Training on Diastolic and Systolic Function After Acute Myocardial Infarction: A Randomized Study. AB - After acute myocardial infarction (AMI), diastolic dysfunction is frequent and an important determinant of adverse outcome. However, few interventions have proven to be effective in improving diastolic function. We aimed to determine the effect of exercise training on diastolic and systolic function after AMI.One month after AMI, 188 patients were prospectively randomized (1:1) to an 8-week supervised program of endurance and resistance exercise training (n = 86; 55.9 +/- 10.8 years) versus standard of care (n = 89; 55.4 +/- 10.3 years). All patients were submitted to detailed echocardiography and cardiopulmonary exercise test, at baseline and immediately after the study. Diastolic function was evaluated by the determination of tissue-Doppler derived early diastolic velocities (E' velocity at the septal and lateral sides of mitral annulus) and by the E/E' (ratio between the E wave velocity from mitral inflow and the E' velocity) as recommended in the consensus document for diastolic function assessment.At the end of the study, there was no significant change in E' septal velocity or E/E' septal ratio in the exercise group. We observed a small, although nonsignificant, improvement in E' lateral (mean change 0.1 +/- 2.0 cm/s; P = 0.40) and E/E' lateral ratio (mean change of -0.3 +/- 2.5; P = 0.24), while patients in the control group had a nonsignificant reduction in E' lateral (mean change -0.4 +/- 1.9 cm/s; P = 0.09) and an increase in E/E' lateral ratio (mean change + 0.3 +/- 3.3; P = 0.34). No relevant changes occurred in other diastolic parameters. The exercise-training program also did not improve systolic function (either tissue Doppler systolic velocities or ejection fraction).Exercise capacity improved only in the exercise training group, with an increase of 1.6 mL/kg/min in pVO2 (P = 0.001) and of 1.9 mL/kg/min in VO2 at anaerobic threshold (P < 0.001).After AMI, an 8-week endurance plus resistance exercise-training program did not significantly improve diastolic or systolic function, although it was associated with an improvement in exercise capacity parameters. PMID- 26356699 TI - The Efficacy and Safety of Chemotherapy in Patients With Nonsmall Cell Lung Cancer and Interstitial Lung Disease: A PRISMA-Compliant Bayesian Meta-Analysis and Systematic Review. AB - Chemotherapy plays a critical and venturous role against the co-morbidity of nonsmall cell lung cancer and interstitial lung disease (NSCLC-ILD).We performed a Bayesian meta-analysis and systematic review to evaluate the safety and efficacy of the chemotherapy in NSCLC-ILD patients.EMBASE, PubMed, the Cochrane Central Register of Controlled Trials, and clinicaltrials.gov (up to January 2015).We included all study designs except case reports, all studies with NSCLC ILD patients and all the possible chemotherapy regimens.Quality was assessed by a components approach. We derived summary estimates using Bayesian method through WinBUGS (version 1.4.3, MRC Biostatistics Unit, Cambridge, UK).Seven studies involving 251 patients with NSCLC-ILD were included in the meta-analysis. The treatment response (complete remission, 0; [partial remission, 39.1%; 95% credible interval [CrI], 32.6-45.7]; [stable disease, 36%; 95% CrI, 29.6-42.2]; [PD, 15.4%; 95% CrI, 11.3-19.8]; [nonevaluable, 6.4%; 95% CrI, 2.7-10.1]; [overall response rate, 41.3%; 95% CrI, 35.3-47.4]; [disease control rate, 77.7%; 95% CrI, 72.2-82.7]) were comparable to that of patients with NSCLC alone; the survival outcomes (median overall survival, median progression-free survival, and 1-year survival rate) were slightly worse, especially the lower 1-year survival rate. Platinum-based doublets as first-line chemotherapy may be related to higher incidence of acute exacerbation-ILD in first line chemotherapy (AE, 8.47%; 95% CrI, 5.04-12.6).The data selection bias and small patient number make the meta analysis of treatment response and conclusions generated from these data inaccurate.The present meta-analysis suggests that chemotherapy might be an effective therapy for patients with NSCLC-ILD, but it might be associated with higher incidence of acute exacerbation. PMID- 26356701 TI - Anesthesia-Related and Perioperative Cardiac Arrest in Low- and High-Income Countries: A Systematic Review With Meta-Regression and Proportional Meta Analysis. AB - The anesthesia-related cardiac arrest (CA) rate is a quality indicator to improve patient safety in the perioperative period. A systematic review with meta analysis of the worldwide literature related to anesthesia-related CA rate has not yet been performed.This study aimed to analyze global data on anesthesia related and perioperative CA rates according to country's Human Development Index (HDI) and by time. In addition, we compared the anesthesia-related and perioperative CA rates in low- and high-income countries in 2 time periods.A systematic review was performed using electronic databases to identify studies in which patients underwent anesthesia with anesthesia-related and/or perioperative CA rates. Meta-regression and proportional meta-analysis were performed with 95% confidence intervals (CIs) to evaluate global data on anesthesia-related and perioperative CA rates according to country's HDI and by time, and to compare the anesthesia-related and perioperative CA rates by country's HDI status (low HDI vs high HDI) and by time period (pre-1990s vs 1990s-2010s), respectively.Fifty-three studies from 21 countries assessing 11.9 million anesthetic administrations were included. Meta-regression showed that anesthesia-related (slope: -3.5729; 95% CI: -6.6306 to -0.5152; P = 0.024) and perioperative (slope: -2.4071; 95% CI: -4.0482 to -0.7659; P = 0.005) CA rates decreased with increasing HDI, but not with time. Meta-analysis showed per 10,000 anesthetics that anesthesia-related and perioperative CA rates declined in high HDI (2.3 [95% CI: 1.2-3.7] before the 1990s to 0.7 [95% CI: 0.5-1.0] in the 1990s-2010s, P < 0.001; and 8.1 [95% CI: 5.1-11.9] before the 1990s to 6.2 [95% CI: 5.1-7.4] in the 1990s-2010s, P < 0.001, respectively). In low-HDI countries, anesthesia-related CA rates did not alter significantly (9.2 [95% CI: 2.0-21.7] before the 1990s to 4.5 [95% CI: 2.4 7.2] in the 1990s-2010s, P = 0.14), whereas perioperative CA rates increased significantly (16.4 [95% CI: 1.5-47.1] before the 1990s to 19.9 [95% CI: 10.9 31.7] in the 1990s-2010s, P = 0.03).Both anesthesia-related and perioperative CA rates decrease with increasing HDI but not with time. There is a clear and consistent reduction in anesthesia-related and perioperative CA rates in high-HDI countries, but an increase in perioperative CA rates without significant alteration in the anesthesia-related CA rates in low-HDI countries comparing the 2 time periods. PMID- 26356700 TI - Performance of Positron Emission Tomography and Positron Emission Tomography/Computed Tomography Using Fluorine-18-Fluorodeoxyglucose for the Diagnosis, Staging, and Recurrence Assessment of Bone Sarcoma: A Systematic Review and Meta-Analysis. AB - To investigate the performance of fluorine-18-fluorodeoxyglucose (F-FDG) positron emission tomography (PET) and PET/computed tomography (CT) in the diagnosis, staging, restaging, and recurrence surveillance of bone sarcoma by systematically reviewing and meta-analyzing the published literature.To retrieve eligible studies, we searched the MEDLINE, Embase, and the Cochrane Central library databases using combinations of following Keywords: "positron emission tomography" or "PET," and "bone tumor" or "bone sarcoma" or "sarcoma." Bibliographies from relevant articles were also screened manually. Data were extracted and the pooled sensitivity, specificity, and diagnostic odds ratio (DOR), on an examination-based or lesion-based level, were calculated to appraise the diagnostic accuracy of F-FDG PET and PET/CT. All statistical analyses were performed using Meta-Disc 1.4.Forty-two trials were eligible. The pooled sensitivity and specificity of PET/CT to differentiate primary bone sarcomas from benign lesions were 96% (95% confidence interval [CI], 93-98) and 79% (95% CI, 63 90), respectively. For detecting recurrence, the pooled results on an examination based level were sensitivity 92% (95% CI, 85-97), specificity 93% (95% CI, 88 96), positive likelihood ratio (PLR) 10.26 (95% CI, 5.99-17.60), and negative likelihood ratio (NLR) 0.11 (95% CI, 0.05-0.22). For detecting distant metastasis, the pooled results on a lesion-based level were sensitivity 90% (95% CI, 86-93), specificity 85% (95% CI, 81-87), PLR 5.16 (95% CI, 2.37-11.25), and NLR 0.15 (95% CI, 0.11-0.20). The accuracies of PET/CT for detecting local recurrence, lung metastasis, and bone metastasis were satisfactory. Pooled outcome estimates of F-FDG PET were less complete compared with those of PET/CT.F FDG PET and PET/CT showed a high sensitivity for diagnosing primary bone sarcoma. Moreover, PET/CT demonstrated excellent accuracy for the staging, restaging, and recurrence surveillance of bone sarcoma. However, to avoid misdiagnosis, pathological examination or long-term follow-up should be carried out for F-FDG avid lesions in patients with suspected bone sarcoma. PMID- 26356702 TI - Type 1 Diabetes and Increased Risk of Subsequent Asthma: A Nationwide Population Based Cohort Study. AB - The association between type 1 diabetes mellitus (T1DM) and asthma remains controversial and has led to new interest in these 2 disorders. The purpose of this study was to examine the associations among young people with T1DM and asthma and offer a clinical demonstration of the balance between Th1 and Th2 responses.We conducted a retrospective cohort study by using data from the National Health Insurance (NHI) system of Taiwan. The cohort consisted of 3545 T1DM cases and 14,180 controls established during the 1998 to 2011 period. Of the 3545 T1DM patients, 55.1% were girls and 26.5% were in the age group <8 years.The overall incidence of asthma was 47% higher in the T1DM cohort than in the control cohort (6.49 vs 4.42 per 1000 person-y), with an adjusted hazard ratio (HR) of 1.34 (95% confidence interval [CI] = 1.11-1.62). Moreover, T1DM patients who visited the emergency room (ER) more than twice for diabetes had a higher adjusted HR of 17.4 (95% CI = 12.9-23.6) of developing asthma. The adjusted HR of asthma was 38.6 (95% CI = 28.5-52.2) in T1DM patients who had been hospitalized more than twice for diabetes.We observed a significantly higher incidence of asthma in young patients with T1DM than in the general population. Among young people of T1DM with more ER visits or frequent hospitalization because of diabetes mellitus were associated with risk of asthma, may indicate that poor glycemic control significantly contributes to asthma risk. PMID- 26356703 TI - Osteochondritis Dissecans Involving the Trochlear Groove Treated With Retrograde Drilling: A Case Report. AB - Osteochondritis dissecans (OCD) occurs frequently in the humeral capitellum of the upper extremity, whereas OCD involving the trochlear groove (trochlear groove OCD) is rarely reported. A standard treatment for trochlear groove OCD has therefore not been determined, although several methods have been tried.The case of a 14-year-old male gymnast with bilateral trochlear groove OCD is presented. Retrograde drilling from the lateral condyle of the humerus was applied for the OCD lesion of the left elbow, since it was larger in size than that in the right elbow and was symptomatic. Conversely, since the right lesion was small and asymptomatic, it was managed conservatively.After treatment, consolidation of the OCD lesions was observed in both elbows. However, the time to healing was shorter in the left elbow treated surgically than in the right elbow managed conservatively.In conclusion, retrograde drilling is a very simple and minimally invasive treatment. This case suggests that retrograde drilling for trochlear groove OCD may be a useful procedure that may accelerate the healing process for OCD lesions. PMID- 26356704 TI - Diagnosis of Testicular Adrenal Rest Tumors on Ultrasound: A Retrospective Study of 15 Cases Report. AB - The aim of this study was to evaluate the imaging features of testicular adrenal rest tumors (TARTs) on baseline ultrasound (BUS).The imaging features of 30 TART lesions pathologically or clinically confirmed in 15 patients who had undergone BUS were evaluated, and the sonographic characteristics of the lesions were analyzed.All 15 cases were bilateral and located near the testicular mediastinum. Approximately 56.7% (17/30) of the TART lesions exhibited homogeneous hypoechogenicity, 36.7% (11/30) of the lesions exhibited heterogeneous hypoechogenicity, and 6.6% (2/30) of the lesions exhibited heterogeneous isoechogenicity. In addition, 76.7% (23/30) of the lesions exhibited a rich blood supply, whereas 23.3% (7/30) of the lesions exhibited a scarce blood supply.The sonographic characteristics of the TARTs were bilateral growth, location adjacent to the testicular mediastinum, hypoechogenicity, and rich blood supply, which may play important roles in early clinical diagnosis. PMID- 26356705 TI - Modified IDSA/ATS Minor Criteria for Severe Community-Acquired Pneumonia Best Predicted Mortality. AB - It is not clear whether the IDSA/ATS minor criteria for severe community-acquired pneumonia (CAP) could be simplified or even be modified to orchestrate improvements in predicting mortality.A retrospective cohort study of 1230 CAP patients was performed to simplify and to modify the scoring system by excluding 4 noncontributory or infrequent variables (leukopenia, hypothermia, hypotension, and thrombocytopenia) and by excluding these variables and then adding age >=65 years, respectively. The simplification and modification were tested against a prospective 2-center validation cohort of 1409 adults with CAP.The increasing numbers of IDSA/ATS, simplified, and modified minor criteria present in the retrospective cohort were positively associated with the mortality, showing significant increased odds ratios for mortality of 2.711, 4.095, and 3.755, respectively. The validation cohort confirmed a similar pattern. The sensitivity, specificity, positive predictive value, and Youden index of modified minor criteria for mortality prediction were the best pattern in the retrospective cohort. High values of corresponding indices were confirmed in the validation cohort. The highest accuracy of the modified version for predicting mortality in the retrospective cohort was illustrated by the highest area under the receiver operating characteristic curve of 0.925 (descending order: modified, simplified, and IDSA/ATS minor criteria). The validation cohort confirmed a similar paradigm.The IDSA/ATS minor criteria could be simplified to 5 variables and then be modified to orchestrate improvements in predicting mortality in CAP patients. The modified version best predicted mortality. These were more suitable for clinic and emergency department. PMID- 26356706 TI - Poor Self-Rated Health Influences Hospital Service Use in Hospitalized Inpatients With Chronic Conditions in Taiwan. AB - Our aim was to investigate the association between self-rated health (SRH) and use of hospital services (ie, medical outpatient department, emergency department, and general ward. admissions). Cross-sectional study data were collected from 230 consecutive patients admitted to medical departments of a 2000 bed academic medical center in Taiwan using standardized operating procedures for data collection of SRH (ie, a single-item question inquiring overall perceived health status), medical disorders, depressive symptoms, and combined service utilization over a 1-year period (ie, number of visits to outpatient department, number of visits to emergency department, and number of hospitalizations). Electronic medical records were retrieved, with self-reported external medical visits added to in-hospital frequencies of service use to provide better estimation of health service utilization. Fifty-two percent of study patients rated their health as poor or very poor. Poor SRH was associated with more visits to medical outpatient department, emergency department, and hospital admission. Multivariate logistic regression demonstrated an independent association between poor SRH and services utilization after adjustment for age, gender, hypertension, diabetes, metastatic cancer, number of chronic illness, life-threatening event, life-time suicidal ideation, and depression. SRH may be a useful research tool to model medical service use for inpatients with chronic conditions. PMID- 26356707 TI - Post-Traumatic Torticollis Due to Odontoid Fracture in a Patient With Diffuse Idiopathic Skeletal Hyperostosis: A Case Report. AB - Descriptive case report.To report a rare case of post-traumatic torticollis by odontoid fracture in a patient with diffuse idiopathic skeletal hyperostosis (DISH).Cervical fractures in DISH can result from minor trauma, and a delay in presentation often prevents their timely diagnosis. Cervical fractures in patients with spinal DISH usually occur in extension injuries, and almost always occur in the lower cervical spine. Reports of odontoid fractures with torticollis in patients with spinal DISH are rare.A 73-year-old man with DISH presented with severe neck pain and a cervical deformity presenting as torticollis without neurological deficits. He gave a history of a fall while riding a bicycle at a low speed 3 months ago. X-ray showed torticollis in the right side, and computed tomography (CT) showed a type-II odontoid fracture and subluxation at the C1-2 level.We performed a staged treatment because this patient had severe neck pain associated with a chronic course. Initially, the fracture dislocation was reduced under general anesthesia and was stabilized with a halo vest. We then performed posterior occipitocervical in situ fusion after confirming the correction of the cervical deformity by CT. The patient showed significant amelioration of neck symptoms postoperatively, and bony fusion was achieved 1 year after surgery.For post-traumatic torticollis due to an odontoid fracture, plain CT is useful for diagnosis and posterior occipitocervical in situ fusion following correction and immobilization with a halo vest is a safe and an effective treatment. PMID- 26356709 TI - Epigenetic Modifications in the Biology of Nonalcoholic Fatty Liver Disease: The Role of DNA Hydroxymethylation and TET Proteins. AB - The 5-Hydroxymethylcytosine (5-hmC) is an epigenetic modification whose role in the pathogenesis of metabolic-related complex diseases remains unexplored; 5-hmC appears to be prevalent in the mitochondrial genome. The Ten-Eleven-Translocation (TET) family of proteins is responsible for catalyzing the conversion of 5 methylcytosine to 5-hmC. We hypothesized that epigenetic editing by 5-hmC might be a novel mechanism through which nonalcoholic fatty liver disease (NAFLD) associated molecular traits could be explained.Hence, we performed an observational study to explore global levels of 5-hmC in fresh liver samples of patients with NAFLD and controls (n = 90) using an enzyme-linked-immunosorbent serologic assay and immunohistochemistry. We also screened for genetic variation in TET 1-3 loci by next generation sequencing to explore its contribution to the disease biology. The study was conducted in 2 stages (discovery and replication) and included 476 participants.We observed that the amount of 5-hmC in the liver of both NAFLD patients and controls was relatively low (up to 0.1%); a significant association was found with liver mitochondrial DNA copy number (R = 0.50, P = 0.000382) and PPARGC1A-mRNA levels (R = -0.57, P = 0.04).We did not observe any significant difference in the 5-hmC nuclear immunostaining score between NAFLD patients and controls; nevertheless, we found that patients with NAFLD (0.4 +/- 0.5) had significantly lower nonnuclear-5-hmC staining compared with controls (1.8 +/- 0.8), means +/- standard deviation, P = 0.028. The missense p.Ile1123Met variant (TET1-rs3998860) was significantly associated with serum levels of caspase-generated CK-18 fragment-cell death biomarker in the discovery and replication stage, and the disease severity (odds ratio: 1.47, 95% confidence interval: 1.10-1.97; P = 0.005). The p.Ile1762Val substitution (TET2 rs2454206) was associated with liver PPARGC1A-methylation and transcriptional levels, and Type 2 diabetes.Our results suggest that 5-hmC might be involved in the pathogenesis of NAFLD by regulating liver mitochondrial biogenesis and PPARGC1A expression. Genetic diversity at TET loci suggests an "epigenetic" regulation of programmed liver-cell death and a TET-mediated fine-tuning of the liver PPARGC1A-transcriptional program. PMID- 26356710 TI - Different Risk of Common Gastrointestinal Disease Between Groups Undergoing Hemodialysis or Peritoneal Dialysis or With Non-End Stage Renal Disease: A Nationwide Population-Based Cohort Study. AB - Peritoneal dialysis (PD) is one type of renal replacement therapy, but potential peritoneal damage and gastrointestinal (GI) tract adverse effects during long term exposure to bio-incompatible dialysate remain a concern. Although GI disease frequently occurs in dialysis patients, whether the risk of GI diseases differs among PD and hemodialysis (HD) or non-uremic groups is still uncertain.In this retrospective cohort study, data were obtained from the National Health Insurance Research Database, which includes almost all dialysis patients in Taiwan. Between 2000 and 2009, a total of 1791 PD and 8955 HD incident patients were enrolled and matched for age and sex or for propensity score. In addition, a comparison cohort of 8955 non-uremic patients was also selected. Individuals were monitored for the occurrence of common GI diseases until 2010, and data were analyzed using several different models.Generally speaking, the results showed that the risk of gastroesophageal reflux, intestinal obstruction or adhesions, and abdominal hernia was significantly higher in the PD group, whereas the risk of peptic ulcer disease and lower GI diverticula and bleeding was significantly greater in the HD group. Meanwhile, the risk of mesenteric ischemia, liver cirrhosis, and acute pancreatitis was higher in dialysis patients, but was not significantly different between the PD and HD groups; moreover, the risk of appendicitis in the PD group appeared to be lower than that in the HD group.In conclusion, dialysis patients have a higher risk of most common GI diseases, and PD and HD modalities are associated with different GI diseases. PMID- 26356708 TI - Competing Risk Analysis for Evaluation of Dalteparin Versus Unfractionated Heparin for Venous Thromboembolism in Medical-Surgical Critically Ill Patients. AB - Failure to recognize the presence of competing risk or to account for it may result in misleading conclusions. We aimed to perform a competing risk analysis to assess the efficacy of the low molecular weight heparin dalteparin versus unfractionated heparin (UFH) in venous thromboembolism (VTE) in medical-surgical critically ill patients, taking death as a competing risk.This was a secondary analysis of a prospective randomized study of the Prophylaxis for Thromboembolism in Critical Care Trial (PROTECT) database. A total of 3746 medical-surgical critically ill patients from 67 intensive care units (ICUs) in 6 countries receiving either subcutaneous UFH 5000 IU twice daily (n = 1873) or dalteparin 5000 IU once daily plus once-daily placebo (n = 1873) were included for analysis.A total of 205 incident proximal leg deep vein thromboses (PLDVT) were reported during follow-up, among which 96 were in the dalteparin group and 109 were in the UFH group. No significant treatment effect of dalteparin on PLDVT compared with UFH was observed in either the competing risk analysis or standard survival analysis (also known as cause-specific analysis) using multivariable models adjusted for APACHE II score, history of VTE, need for vasopressors, and end-stage renal disease: sub-hazard ratio (SHR) = 0.92, 95% confidence interval (CI): 0.70-1.21, P-value = 0.56 for the competing risk analysis; hazard ratio (HR) = 0.92, 95% CI: 0.68-1.23, P-value = 0.57 for cause-specific analysis. Dalteparin was associated with a significant reduction in risk of pulmonary embolism (PE): SHR = 0.54, 95% CI: 0.31-0.94, P-value = 0.02 for the competing risk analysis; HR = 0.51, 95% CI: 0.30-0.88, P-value = 0.01 for the cause specific analysis. Two additional sensitivity analyses using the treatment variable as a time-dependent covariate and using as-treated and per-protocol approaches demonstrated similar findings.This competing risk analysis yields no significant treatment effect on PLDVT but a superior effect of dalteparin on PE compared with UFH in medical-surgical critically ill patients. The findings from the competing risk method are in accordance with results from the cause-specific analysis.clinicaltrials.gov Identifier: NCT00182143. PMID- 26356711 TI - Combined Lacrimal Passage Probing and Tobramycin/Dexamethasone Ophthalmic Ointment Infiltration: A Minimally Invasive Surgical Procedure for Incomplete Nasolacrimal Duct Obstruction. AB - The optimal treatment strategy for an incomplete nasolacrimal duct obstruction (INDO) is still being debated. The aim of this study is to evaluate the treatment results of combined lacrimal passage probing and tobramycin/dexamethasone ophthalmic ointment infiltration (PIO, Probing and Injection) for INDO.In this retrospective, noncomparative case series, 397 consecutive adult patients with INDO treated at Shanghai Eye, Ear, Nose and Throat Hospital were enrolled. Records of the patients were reviewed. With the help of a modified 23-gauge lacrimal cannula, the PIO surgery was performed for the INDO-identified patients. The main outcome measures were resolution of tearing and complications. The relationship between successful outcome and clinical characteristics was analyzed.The surgery was performed successfully in all of the enrolled cases. No intraoperative complications were found in the procedure. The average follow-up time was 7.9 months. Three hundred patients (75.6%) experienced complete resolution of their symptoms after the surgery. Ninety-seven patients (24.4%) showed a partial improvement (1.8%), no improvement (18.4%), or a worsening of symptoms (4.3%). Of the 97 surgical-failure patients, 90 required silicone intubation or external dacryocystorhinostomy, and 94% were finally resolved. The most common postoperative complications were mild nasal bleeding in 41 patients, drug residues in 12 patients (6 developed the complete obstruction), and a slit punctum in 8 patients. Multivariate logistic regression analysis revealed that unilateral eye onset, not having a discharge at baseline, and not having postoperative drug residues were significant factors determining successful outcome.The PIO surgery is an effective, safe, timesaving, easy-to-perform, and minimally invasive technique for treating INDO. PMID- 26356712 TI - Metachronous Primary Adenocarcinoma of Lung During Adjuvant Imatinib Mesylate Therapy for Gastrointestinal Stromal Tumor of Stomach: A Case Report. AB - Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor in gastrointestinal tracts; however, the synchronous or metachronous coexistence of GIST with additional primary malignancy is not common.Here, we present an unusual case of gastric GIST with metachronous primary lung adenocarcinoma diagnosed during his adjuvant treatment with oral receptor tyrosine kinase inhibitor imatinib mesylate (400 mg daily). After 6-month use of imatinib, the patient suffered from dry cough and dyspnea. Subsequent lung biopsy demonstrated adenocarcinoma with diffuse interstitial changes.Our research emphasizes the possibility of an additional primary tumor with GIST, and reminds the clinicians to strengthen the surveillance of the additional cancer during the follow-up of GIST patients. PMID- 26356713 TI - A Large-Scale Study Indicates Increase in the Risk of Epilepsy in Patients With Different Risk Factors, Including Rheumatoid Arthritis. AB - Peripheral neuropathy and inflammatory reactions of the central nervous system may accompany rheumatoid arthritis (RA). Inflammatory processes play a critical role in epilepsy. Therefore, we conducted this study to determine the risk of epilepsy in patients with RA.The RA cohort comprised patients ages 20 years and older who were newly diagnosed with RA between 2000 and 2011, with data obtained from the Registry of Catastrophic Illnesses Patient Database. Patients without RA were frequency matched with an RA cohort at a 1:1 ratio according to age, sex, and year of RA diagnosis.The overall crude hazard ratio (HR) for epilepsy was 1.27-fold higher in the RA cohort compared with that in the controls. After adjustment for age, sex, comorbidities, and medications, the patients with RA were associated with an increased risk of epilepsy compared with those without RA (adjusted HR [aHR] = 1.52, 95% confidence interval [CI] = 1.12-2.07). Compared with the RA patients with <= 560 days of nonsteroidal anti-inflammatory drug (NSAID) use, the RA patients with 1181 to 2145 and >2145 days of NSAID use had a significantly lower risk of epilepsy (aHR = 0.35, 95% CI = 0.24-0.52 and aHR = 0.15, 95% CI = 0.09-0.24, respectively).This study provides compelling evidence of an increased risk of epilepsy in patients with RA. The period of NSAID treatment is negatively associated with the risk of epilepsy in RA patients. PMID- 26356714 TI - Prognostic Value of the Modified Glasgow Prognostic Score in Patients Undergoing Radical Surgery for Hepatocellular Carcinoma. AB - There is increasing and consistent evidence concerning the association of systemic inflammation and poor outcome in patients with hepatocellular carcinoma (HCC). The aim of this study was to identify a superior inflammation-based prognostic scoring system for patients with HCC undergoing hepatectomy.We analyzed two independent cohorts of a total of 723 patients with HCC who underwent radical surgery between 2010 and 2012. The prognostic value of the inflammation scores, including the Glasgow Prognostic Score (GPS), modified GPS (mGPS), neutrophil-to-lymphocyte ratio, platelet lymphocyte ratio, prognostic index, and prognostic nutritional index, as well as the Barcelona Clinic Liver Cancer and Cancer of the Liver Italian Program staging systems was analyzed in a test cohort of 367 patients and validated in a validation cohort of 356 patients.A high score with the mGPS was associated with large tumor size, vascular invasion, and advanced clinical stage. Multivariate analysis showed that the mGPS was independently associated with overall survival and disease-free survival, and had a higher area under the curve value in comparison with other inflammation-based scores.The results of this study demonstrated that the mGPS is an independent marker of poor prognosis in patients with resectable HCC and is superior to other inflammation-based scores. PMID- 26356715 TI - Antihypertensive Drug Use and New-Onset Diabetes in Female Patients with Coronary Artery Disease: A Population-based Longitudinal Cohort Study. AB - Antihypertensives have been linked to new-onset diabetes (NOD) and different classes of antihypertensives may alter the risk for the development of NOD; however, the effect of different antihypertensives on the development of NOD in women with hypertension and coronary artery disease (CAD) has not been well studied. The purpose of this study is to investigate the association between usage of different antihypertensive drugs and the development of NOD in female patients with hypertension and CAD.Data in this retrospective cohort study were obtained from claim forms submitted to the Taiwan Bureau of National Health Insurance in central Taiwan during the period 2006-2011. We estimated the odds ratios (OR) to approximate the relative risk of NOD development associated with antihypertensive drug use.Of the 20,108 female patients with CAD at baseline, 2288 patients developed NOD during the 6-year follow-up. Subjects treated with angiotensin-converting enzyme (ACE) inhibitors (OR, 0.92; 95% confidence interval [CI], 0.84-1.00), angiotensin receptor blockers (OR, 0.92; 95% CI, 0.82-0.99), and alpha-blockers (OR, 0.88; 95% CI, 0.79-0.98) in the adjusted analyses had greater reductions of the risk than among nonusers. Patients who took diuretics (OR, 1.10; 95% CI, 1.01-1.20), beta-blockers (OR, 1.12; 95% CI, 1.04-1.21), and calcium channel blockers (OR, 1.10; 95% CI, 1.02-1.18) were at high risk of developing NOD than nonusers. Vasodilators were not associated with risk of NOD.We conclude that women with hypertension who take ACE inhibitors, angiotensin receptor blockers, and alpha-blockers are at lower risk of NOD and that use of diuretics, beta-blockers, and calcium channel blockers was associated with a significantly increased risk of developing NOD during the 6-year follow-up. PMID- 26356716 TI - Irritable Bowel Syndrome Increases the Risk of Epilepsy: A Population-Based Study. AB - An abnormal interaction in the brain-gut axis is regarded as the cause of irritable bowel syndrome (IBS). We attempted to determine the association between IBS and subsequent development of epilepsy.A total of 32,122 patients diagnosed with IBS between 2000 and 2011 were identified from the Longitudinal Health Insurance Database as the study cohort, and 63,295 controls were randomly selected from the insurants without IBS and frequency-matched according to age, sex, and index year as the comparison cohort. Both cohorts were followed up until the end of 2011 to measure the incidence of epilepsy. We analyzed the risks of epilepsy using Cox proportional hazards regression models.The IBS patients had greater cumulative incidence of epilepsy than the cohort without IBS (log-rank test, P < 0.001 and 2.54 versus 1.86 per 1000 person-years). The IBS cohort had a higher risk of epilepsy after adjusting for age, sex, diabetes, hypertension, stroke, coronary artery disease, head injury, depression, systemic lupus erythematosus, brain tumor, and antidepressants usage (adjusted hazard ratio [aHR]: 1.30, 95% confidence interval [CI]: 1.17-1.45). Stratified by the presence of other risk factors, the relative risk was also greater for patients with (aHR: 1.25, 95% CI: 1.10-1.41) or without other risk factors (aHR: 1.68, 95% CI: 1.35 2.10) in the IBS cohort than for those in the non-IBS cohort. The age-specific relative risk of epilepsy in the IBS cohort was greater than that in the non-IBS cohort for both 35 to 49 age group and 50 to 64 age group (age <= 34, aHR:1.31, 95% CI: 0.93-1.85; age 35-49, aHR: 1.43, 95% CI: 1.12-1.83; age 50-64, aHR: 1.56, 95% CI: 1.27-1.91). However, there was no difference between patients > 65 years with IBS and those without IBS (aHR: 1.11, 95% CI: 0.94-1.31).This population based cohort study revealed that IBS increases the risk of developing epilepsy. However, IBS may be less influential than other risk factors. Further study is necessary to clarify whether IBS is a risk factor or an epiphenomenon for epilepsy development. PMID- 26356717 TI - Subacute Pain as a Predictor of Long-Term Pain Following Orthopedic Surgery: An Australian Prospective 12 Month Observational Cohort Study. AB - The aim of this study was to document the level of pain and functionality in the 12 months following orthopedic surgery and identify if high pain levels following discharge were associated with pain persisting at 12 months.An observational prospective cohort study was undertaken, following 87 patients (mean age 62.4 years [18-92]; 47.1% male) who required orthopedic surgery at the Royal Hobart Hospital, Australia. Following an initial survey, patients were telephoned at 10 days, 6 weeks, 3 months, and 12 months after discharge.Postdischarge pain levels were high with 97.4% of patients suffering pain at 10 days, 81.2% at 6 weeks and 79.5% at 3 months. Pain affected the ability to undertake activities of daily living (ADLs) for 32.7% and 20.0% of patients at 10 days and 6 weeks, respectively. Twelve months after discharge, 65.5% of patients reported pain persisting at the surgical site, with 29.9% of all patients suffering moderate severe incidental pain; and nearly one quarter of patients reported pain affected their sleep or ADLs. Average pain levels rated as moderate-severe at 10 days (P = 0.01) and 6 weeks (P = 0.02) and pain of neuropathic origin at 3 months (30.2% vs 10.3% P = 0.03) and 12 months (30.4% vs 4.9% P = 0.01) were associated with persistent pain at 12 months.Pain in the period following discharge from hospital is significant and undermanaged. Previous studies has shown that that acute pain, particularly in the first 48 hours following surgery is a predictor for long-term pain after surgery. This study adds to the current literature by showing that pain in the subacute period, following discharge from hospital is also associated with the pain persisting at 12 months. These findings have important implications for improving quality of life as well as potentially preventing persistent pain with increased follow-up and more intensive management of post-discharge pain. PMID- 26356718 TI - The Diagnostic Value of Superb Microvascular Imaging (SMI) in Detecting Blood Flow Signals of Breast Lesions: A Preliminary Study Comparing SMI to Color Doppler Flow Imaging. AB - The correlation between color Doppler flow imaging (CDFI) and Superb Microvascular Imaging (SMI) for detecting blood flow in breast lesions was investigated, as was the diagnostic value of SMI in differentiating benign from malignant breast lesions.These lesions were evaluated using both CDFI and SMI according to Adler's method. Pathologic examination showed 57 malignant lesions and 66 benign lesions. The number of blood vessels in a single mass was detected by 2 techniques (SMI and CDFI), and the difference between the 2 values (SMI CDFI) was calculated. The optimal threshold for the diagnosis of malignant neoplasms and the diagnostic performances of SMI, CDFI, and SMI-CDFI were calculated.For the total lesions and malignant lesions alone, the difference between SMI and CDFI for detecting blood flow was significant (P < 0.01), but the difference was not significant for benign lesions (P = 0.15). The area under the receiver operating characteristic curve was 0.73 (95% confidence interval [CI]: 0.64-0.82) for CDFI; 0.81 (95% CI: 0.74-0.89) for SMI; and 0.89 (95% CI: 0.82 0.95) for SMI-CDFI. Furthermore, the modality of "SMI-CDFI" showed the best diagnostic performance.SMI provides further microvessel information in breast lesions. The diagnostic modality of "SMI-CDFI" can improve the diagnostic performance of ultrasound in the differentiation between benign and malignant masses. PMID- 26356719 TI - Adipokine CTRP-5 as a Potential Novel Inflammatory Biomarker in Chronic Obstructive Pulmonary Disease. AB - Local and systemic inflammation often present in chronic obstructive pulmonary disease (COPD). Adipokines are secretory protein mediators by adipose tissue, which have been found to involve in inflammatory responses in many chronic inflammatory diseases. Therefore, we performed this preliminary clinical study to investigate the possible association between 2 adipokines, C1q/tumor necrosis factor-related protein-3 and -5 (CTRP-3 and CTRP-5), with lung function and other markers of inflammation in COPD. Serum CTRP-3 and CTRP-5 levels were measured in 73 COPD patients and 54 health controls, together with lung function and levels of adiponectin, CRP, TNF-alpha, and MPO in both groups. Pearson's partial correlation was used to analyze the correlations between CTRPs and other serum markers or lung function. Serum CTRP-5 was significantly elevated in COPD patients (0.41 +/- 0.35 versus 0.29 +/- 0.28 MUg/ml, P = 0.01) and correlated inversely with FEV1/FVC ratio in all patients (r = -0.31, P = 0.001). In COPD patients, CTRP-5 was also correlated negatively with FEV1% predicted (r = -0.464, P < 0.001) and had a positive association with CRP levels (r = 0.262, P = 0.04). However, serum CTRP-3 levels were not correlated with measures of lung function or systemic inflammation. In conclusion, circulating CTRP-5 was associated with the severity of airflow obstruction and systemic inflammation in patients with COPD, which suggests that it may be used as a potential novel inflammatory biomarker in COPD. Further studies should be performed to clarify the exact role of CTRP-5 on the pathogenesis and outcomes of COPD. PMID- 26356720 TI - Association of Migraine and Sleep-Related Breathing Disorder: A Population-Based Cohort Study. AB - In this nationwide population-based cohort study, we aimed to evaluate the effects of sleep-related breathing disorders (SBD) on migraine development.Patients ages 20 years or more and diagnosed with SBD between 2000 and 2009 were evaluated as the SBD cohort (n = 3411), and compared with comparison cohort (n = 13,644). The adjusted hazard ratio (aHR) for developing migraine was calculated in both cohorts by multivariate Cox proportional hazards model.The cumulative incidence of migraine was significantly higher in the SBD cohort than in the comparison cohort. In the SBD cohort, the overall aHR for developing migraine was 2.43 (95% confidence interval [CI] = 1.72-3.44). The risk of developing migraine was higher in men (aHR 2.71) than in women (aHR 2.29) with SBD. When stratifying by age, we observed increased incidence of migraine in patients ages 20 to 44 years and 45 to 64 years, with a higher aHR of 2.51 (95% CI = 1.47-4.30) and 2.68 (95% CI = 1.63-4.43), respectively. The risk of developing migraine in the patients with SBD with or without comorbidity exhibited nonsignificant differences. After stratifying by the use of hypnotics, the aHR for developing migraine was 2.39 in the patients with hypnotics use and 3.58 in the patients without hypnotics use.Our findings indicate increased risk of developing migraine in adults, but not elderly ones, with SBD. PMID- 26356721 TI - Meta-Analyses of Manganese Superoxide Dismutase Activity, Gene Ala-9Val Polymorphism, and the Risk of Schizophrenia. AB - Schizophrenia is a complex and disabling psychiatric disorder, and tardive dyskinesia (TD) is a severe adverse drug effect occurring in 20% to 40% of schizophrenic patients chronically treated with typical neuroleptics. Previous studies suggested that the manganese superoxide dismutase (MnSOD) activity was associated with the development of schizophrenia. Ala-9Val polymorphism, a functional polymorphism of MnSOD gene, has been reported to be related to the risk of schizophrenia and TD. However, these studies did not lead to consistent results. We performed meta-analyses aiming to assess the association between MnSOD activity and schizophrenia, as well as the association of MnSOD Ala-9Val polymorphism with schizophrenia and TD in schizophrenic patients.We search for the literature on MnSOD and schizophrenia in English or Chinese published up to May 1, 2015 on PubMed, EMBASE, the Cochrane Databases, Chinese National Knowledge Infrastructure, China Biology Medical and Wanfang databases. Two investigators independently reviewed retrieved literature and evaluated eligibility. Discrepancy was resolved by consensus with a third reviewer. Data were pooled using fixed-effect or random-effect models. The standardized mean difference (SMD) and 95% confidence interval (CI) were calculated for the MnSOD activity. Pooled odds ratio (OR) and 95% CI were calculated for Ala-9Val genotype and allele frequencies.There were 6, 6, and 10 studies entering 3 parts of meta analyses, respectively. The MnSOD activity of patients was significantly lower than that of controls (SMD = -0.94; 95% CI: -1.76, -0.12; P = 0.025). No significant associations of Ala-9Val genotypes (OR = 1.14; 95% CI: 0.97, 1.33; P = 0.109) and alleles (OR = 1.06; 95% CI: 0.94, 1.20; P = 0.361) with the risk of schizophrenia were observed. We also did not reveal significant associations of the genotypes (OR = 0.82; 95% CI: 0.66, 1.02; P = 0.075) and alleles (OR = 0.90; 95% CI: 0.76, 1.06; P = 0.215) with the risk of TD in schizophrenia.The decreased MnSOD activity may be associated with the risk of chronic schizophrenia in Chinese population, while MnSOD Ala-9Val polymorphism may not play a significant role in the development of schizophrenia and TD. Longitudinal studies with larger sample sizes and different ethnicities are needed to confirm the association of the MnSOD Ala-9Val variants with schizophrenia and TD. PMID- 26356722 TI - Late HIV Diagnosis: Proposed Common Definitions and Associations With Short-Term Mortality. AB - The aim of this study was to present a definition of late presentation according to different time periods between initial diagnosis of human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS) diagnosis which would reliably identify individuals with high risk of mortality within 1 year of diagnosis, and could be used as a suggested common definition.Data of individuals diagnosed from 1994 to February 2012 in Wuhan, China were extracted retrospectively from the national HIV surveillance system. Four time periods (1, 3, 6, and 12 months) combined with the European consensus definition of advanced HIV disease (AHD) were compared. The predictive ability of each definition for identifying an individual who died within 1 year after HIV diagnosis was assessed.A total of 980 patients were included, of whom 289 (29.49%), 324 (33.06%), 353 (36.02%), and 387 (39.49%) were defined as AHD according to the definition of a CD4 count <200 cells/MUL or AIDS-defining event (ADE) within 1, 3, 6, and 12 months of HIV diagnosis, respectively. One hundred twenty-seven (12.96%) patients died within 1 year of diagnosis. The highest Youden's index and largest area under the curve were presented in time period within 3 months. Time period within 1 month presented the highest consistency rate, positive likelihood ratio, and kappa value. Longer time periods increased the sensitivity but decreased the specificity.Given the European consensus definitions and the current results, we suggested that AHD could be defined as "a first-reported CD4 count <200 cells/MUL or an ADE within 1 month after HIV diagnosis." "Late presentation" could be defined as "a first-reported CD4 count <350 cells/MUL or an ADE within 1 month after HIV diagnosis." PMID- 26356723 TI - Vision Loss by Central Retinal Vein Occlusion After Kaatsu Training: A Case Report. AB - Kaatsu training is an exercise method involving the application of pressure to the target muscle, and is being increasingly used in rehabilitation programs for heart disease patients in some hospitals. This method restricts blood flow to the muscles during exercise, and the resultant hypoxia effectively causes muscle hypertrophy and strengthening. However, no medical guidelines or risk factors for its use have been established.We report a case involving a 45-year-old man who suffered from 2 episodes of central retinal vein occlusion (CRVO), both occurring on the day following a Kaatsu training session.As a characteristic of the CRVO and its subsequent complications, the affected eye lost vision despite treatment. The patient had a history of hypertension and diabetes, and thus was at an increased risk of CRVO. Kaatsu training, which changes the heart rate and serum growth hormone levels, may have triggered the onset of CRVO.This case highlights that underlying medical conditions such as hypertension, diabetes, and the consequent inflammation, could be risk factors for vascular side effects resulting from Kaatsu training. Further studies are required before the medical and recreational use of Kaatsu training become widespread. PMID- 26356724 TI - Presentation and Management Outcomes of Corneal and Scleral Perforations in Geriatric Nursing Home Residents. AB - We compared the clinical presentation and treatment outcomes of corneal and scleral perforations in geriatric nursing home residents, geriatric community residents, and non-geriatric population. The medical records of patients who were treated for corneal and scleral perforations at the Prince of Wales Hospital, Hong Kong between January 1, 2004 and May 1, 2013, were reviewed retrospectively. Of 144 cases, 53 (37%) occurred in the geriatric population, of which 16 (11%) lived in nursing homes, and 37 (26%) were community residents. There were 91 (63%) patients in the non-geriatric group. The mean age of the patients in nursing home geriatric group was 86.5 years (87.5% females). The most common etiology of perforation was trauma. Rupture due to fall was more common in geriatric patients (P < 0.001) whereas laceration due to penetrating eye injury was more common in non-geriatric patients (P < 0.001). There were more cases of infection leading to spontaneous perforation in geriatric nursing home group compared to the other groups (P = 0.001). In the geriatric nursing home group, visual acuity at presentation (P < 0.001) and postoperative visual acuity (P = 0.012) was worse compared to the other groups. Our study showed that corneal and scleral perforations in the geriatric nursing home residents carry a poor visual prognosis. The causes and anatomical outcomes of such events in geriatric age group differ from those in the general population. In our study, geriatric patients residing in nursing homes had worse baseline as well as posttreatment visual acuity, compared to community residents. PMID- 26356725 TI - Parental Attitudes and Factors Associated With Varicella Vaccination in Preschool and Schoolchildren in Hong Kong: A Cross-Sectional Study. AB - This study investigates parental attitudes and factors associated with varicella vaccination among preschool and schoolchildren prior to introduction of the vaccine into Hong Kong's universal Childhood Immunization Program.Fourteen kindergartens and 5 primary schools in Hong Kong were randomly selected in 2013. Parents of the students were invited to answer the self-administered questionnaires. Acquired information included demographic characteristics and socioeconomic statuses of families, children's history of chickenpox infection and vaccination, and reasons for getting children vaccinated. Logistic regression was applied to examine the factors associated with vaccination.From the 3484 completed questionnaires, the calculated rates of varicella infection and vaccination were 20.7% and 69.0%, respectively. Barriers to vaccination included parental uncertainties about vaccine effectiveness, lack of recommendation from the government, and concerns on adverse effects. Overall, 71.8%, 69.0%, and 45.7% of the parents rated family doctors, specialists, and the government, respectively, as very important motivators of vaccination. Higher parental educational level and family income, better perceived knowledge of varicella and chance of infection, discussion with a family doctor, and positive health belief towards vaccination were associated with vaccination (all P < 0.05).The rate of vaccination in Hong Kong was higher than that of some other countries that also did not include the vaccine in their routine immunization programs. More positive parental attitudes, higher socioeconomic status, and discussion with a family doctor are associated with greater vaccination rates. The important roles that health professionals and the government play in promoting varicella vaccination were emphasized. PMID- 26356726 TI - Epidemiology and Medication Utilization Pattern of Aortic Dissection in Taiwan: A Population-Based Study. AB - Acute aortic dissection (AD) is a catastrophic condition associated with a high rate of mortality. However, current epidemiological information regarding AD remains sparse. The objective of the present study was to investigate the current epidemiological profile and medication utilization patterns associated with aortic dissection in Taiwan.In this population-based study, we identified cases of AD diagnosed during 2005 to 2012 in the complete Taiwan National Health Insurance (NHI) Research Database. Patients with AD were identified using the International Classification of Disease, Ninth Revision (ICD-9) code 441.0, and surgical interventions were defined using NHI procedure codes.A total of 9092 individuals with a mean age of 64.4 +/- 15.1 years were identified. The cases were divided into 3 groups: Group A included 2340 patients (25.74%) treated surgically for type A AD; Group B included 1144 patients (12.58%) treated surgically for type B AD, and Group C included 5608 patients (61.68%) with any type of AD treated with medical therapy only. The average annual incidence of AD was 5.6 per 100,000 persons, and the average prevalence was 19.9 per 100,000 persons. Hypertension was the most common risk factor, followed by coronary artery disease and chronic obstructive pulmonary disease. Within 1 year of AD diagnosis, 92% of patients were taking antihypertensive medication. Calcium channel blockers were the most frequently prescribed antihypertensive medication for long-term observation in Taiwan.The annual trends revealed statistically significant increases in the numbers and percentages of prevalence, incidence, and mortality. Changes in patients' drug utilization in patterns were observed after AD diagnosis. Our study provides a local profile that supports further in depth analyses in AD-affected populations. PMID- 26356727 TI - The Prognostic Effect of Statin Use on Urologic Cancers: An Updated Meta-Analysis of 35 Observational Studies. AB - Recent studies suggest that statin may benefit cancer prognosis, especially through its radiosensitization effect. But controversy exists in other studies. Hence, we performed a meta-analysis of results from 35 studies to evaluate the effect of statin use on urologic cancers.We conducted computerized search from PubMed, Embase, and ISI Web of Knowledge through May 2015, screened the retrieved references, and collected and evaluated relevant information. We extracted and synthesized corresponding hazard ratios (HR) and confidence interval (CI) by using Review Manager 5.3 and STATA 13. This review was registered at PROSPERO with registration No. CRD42015020171.We selected total 35 retrospective studies and conducted a meta-analysis of results from these studies. The pooled results suggested no benefit of statin use to bladder cancer and renal cell carcinoma, except overall survival [HR = 0.81, 95% CI: 0.69-0.96]. However, significant improvement of prostate cancer prognosis including overall survival [HR = 0.82, 95% CI: 0.70-0.97] and cancer-specific survival [HR = 0.70, 95% CI: 0.59-0.83] was indicated, but not including tumor progression [HR = 0.84, 95% CI: 0.62 1.14]. Statin use improved biochemical recurrence of prostate cancer in radiotherapy patients [HR = 0.68, 95% CI: 0.54-0.85] but not in radical prostatectomy patients [HR = 0.97, 95% CI: 0.82-1.15].Current evidence suggests no benefit of statin use to bladder cancer and renal cell carcinoma, except in overall survival. While statin use benefited prostate cancer patients in overall survival, cancer-specific survival but not in tumor progression; it also improved biochemical recurrence in radiotherapy patients but not in radical patients. To verify these results, randomized controlled trials are necessary. PMID- 26356728 TI - Usefulness of Glycemic Gap to Predict ICU Mortality in Critically Ill Patients With Diabetes. AB - Stress-induced hyperglycemia (SIH) has been independently associated with an increased risk of mortality in critically ill patients without diabetes. However, it is also necessary to consider preexisting hyperglycemia when investigating the relationship between SIH and mortality in patients with diabetes. We therefore assessed whether the gap between admission glucose and A1C-derived average glucose (ADAG) levels could be a predictor of mortality in critically ill patients with diabetes.We retrospectively reviewed the Acute Physiology and Chronic Health Evaluation II (APACHE-II) scores and clinical outcomes of patients with diabetes admitted to our medical intensive care unit (ICU) between 2011 and 2014. The glycosylated hemoglobin (HbA1c) levels were converted to the ADAG by the equation, ADAG = [(28.7 * HbA1c) - 46.7]. We also used receiver operating characteristic (ROC) curves to determine the optimal cut-off value for the glycemic gap when predicting ICU mortality and used the net reclassification improvement (NRI) to measure the improvement in prediction performance gained by adding the glycemic gap to the APACHE-II score.We enrolled 518 patients, of which 87 (17.0%) died during their ICU stay. Nonsurvivors had significantly higher APACHE-II scores and glycemic gaps than survivors (P < 0.001). Critically ill patients with diabetes and a glycemic gap >=80 mg/dL had significantly higher ICU mortality and adverse outcomes than those with a glycemic gap <80 mg/dL (P < 0.001). Incorporation of the glycemic gap into the APACHE-II score increased the discriminative performance for predicting ICU mortality by increasing the area under the ROC curve from 0.755 to 0.794 (NRI = 13.6%, P = 0.0013).The glycemic gap can be used to assess the severity and prognosis of critically ill patients with diabetes. The addition of the glycemic gap to the APACHE-II score significantly improved its ability to predict ICU mortality. PMID- 26356729 TI - Influences of Preparedness Knowledge and Beliefs on Household Disaster Preparedness. AB - In response to concern about strengthening the nation's ability to protect its population and way of life (i.e., security) and ability to adapt and recover from emergencies (i.e., resilience), the President of the United States issued Presidential Policy Directive 8: National Preparedness (PPD-8) (1). Signed on March 30, 2011, PPD-8 is a directive for the U.S. Department of Homeland Security to coordinate a comprehensive campaign across government, private and nonprofit sectors, and individuals to build and sustain national preparedness. Despite efforts by the Federal Emergency Management Agency (FEMA) and other organizations to educate U.S. residents on becoming prepared, growth in specific preparedness behaviors, including actions taken in advance of a disaster to be better prepared to respond to and recover, has been limited (2). In 2012, only 52% of U.S. residents surveyed by FEMA reported having supplies for a disaster (2), a decline from 57% who reported having such supplies in 2009 (3). It is believed that knowledge influences behavior, and that attitudes and beliefs, which are correlated with knowledge, might also influence behavior (4). To determine the association between knowledge and beliefs and household preparedness, CDC analyzed baseline data from Ready CDC, a personal disaster preparedness intervention piloted among Atlanta- and Morgantown-based CDC staff members during 2013-2015. Compared with persons with basic preparedness knowledge, persons with advanced knowledge were more likely to have assembled an emergency kit (44% versus 17%), developed a written household disaster plan (9% versus 4%), and received county emergency alert notifications (63% versus 41%). Similarly, differences in household preparedness behaviors were correlated with beliefs about preparedness. Persons identified as having strong beliefs in the effectiveness of disaster preparedness engaged in preparedness behaviors at levels 7%-30% higher than those with weaker preparedness beliefs. Understanding the influences of knowledge and beliefs on household disaster preparedness might provide an opportunity to inform messages promoting household preparedness. PMID- 26356730 TI - Eye Bank Association of America Medical Standards Regarding Ebola Policy. PMID- 26356731 TI - Risk and Protective Factors for Small Intestine Neuroendocrine Tumors: A Prospective Case-Control Study. AB - BACKGROUND: The incidence of small intestine neuroendocrine tumors (SI-NETs) is increasing, but few studies have investigated risk factors for their occurrence, suggesting that family history (FH) of any cancer, smoking and previous cholecystectomy are associated with an increased risk. Such studies investigated small series or examined cancer registries without direct interviews. AIM: We therefore aimed at clarifying risk and protective factors for the occurrence of sporadic SI-NETs. SUBJECTS AND METHODS: We performed a multicenter case-control study. Patients with a histologic diagnosis of SI-NETs were prospectively evaluated, excluding familial syndromes. Controls with non-neoplastic/non-chronic disorders seen at gastrointestinal outpatients clinics were matched for sex and age (4:1). All subjects were directly interviewed by means of a specific questionnaire on potential risk and protective factors. Cases and controls were compared by Fisher's test or Student's t test for categorical or continuous variables. Explanatory variables were analyzed by simple logistic regression analysis. A multiple logistic regression analysis was performed with an Enter model; p < 0.05 was considered significant. RESULTS: 215 SI-NET patients and 860 controls were enrolled. FH of colorectal cancer (CRC) (8.8 vs. 5.0%) and breast cancer (10.2 vs. 4.8%), heavy smoking (24.7 vs. 14.8%) and drinking >21 alcohol units per week (7.4 vs. 3.8%) were all significantly more frequent in SI-NET patients than in controls. Multivariate analysis showed that FH of CRC (OR 2.23, 95% CI 1.29-3.84, p = 0.003), FH of breast cancer (OR 2.05, 95% CI 1.13-3.69, p = 0.01) and smoking (OR 1.47, 95% CI 1.07-2.03, p = 0.01) and in particular heavy smoking (OR 1.94, 95% CI 1.29-3.84, p = 0.0008) were associated with an increased risk for carcinoid occurrence, while use of aspirin can be considered a protective factor (OR 0.20, 95% CI 0.06-0.65, p = 0.008). CONCLUSION: FH of colorectal and breast cancer as well as smoking seem to be risk factors for the development of SI-NETs, while use of aspirin might be a protective factor. These factors partially overlap with those associated with CRC, but are different from those previously associated with pancreatic neuroendocrine tumors. These findings may suggest that the mechanisms of carcinogenesis for endocrine cells in different sites can be specific and similar to those of their exocrine counterparts. PMID- 26356732 TI - Ten Simple Rules for a Computational Biologist's Laboratory Notebook. PMID- 26356733 TI - A Metagenomic Investigation of the Duodenal Microbiota Reveals Links with Obesity. AB - BACKGROUND: Few studies have tested the small intestine microbiota in humans, where most nutrient digestion and absorption occur. Here, our objective was to examine the duodenal microbiota between obese and normal volunteers using metagenomic techniques. METHODOLOGY/PRINCIPAL FINDINGS: We tested duodenal samples from five obese and five normal volunteers using 16S rDNA V6 pyrosequencing and Illumina MiSeq deep sequencing. The predominant phyla of the duodenal microbiota were Firmicutes and Actinobacteria, whereas Bacteroidetes were absent. Obese individuals had a significant increase in anaerobic genera (p < 0.001) and a higher abundance of genes encoding Acyl-CoA dehydrogenase (p = 0.0018) compared to the control group. Obese individuals also had a reduced abundance of genes encoding sucrose phosphorylase (p = 0.015) and 1,4-alpha glucan branching enzyme (p = 0.05). Normal weight people had significantly increased FabK (p = 0.027), and the glycerophospholipid metabolism pathway revealed the presence of phospholipase A1 only in the control group (p = 0.05). CONCLUSIONS/SIGNIFICANCE: The duodenal microbiota of obese individuals exhibit alterations in the fatty acid and sucrose breakdown pathways, probably induced by diet imbalance. PMID- 26356734 TI - Gene Expression and MicroRNA Expression Analysis in Small Arteries of Spontaneously Hypertensive Rats. Evidence for ER Stress. AB - Small arteries are known to develop functional and structural alterations in hypertension. However, the mechanisms of this remodeling are not fully understood. We hypothesized that altered gene expression is associated with the development of hypertension in mesenteric arteries of spontaneously hypertensive rats (SHR). Three sublines of SHR and normotensive Wistar Kyoto rats (WKY) were studied at 6 weeks and 5 months of age. MiRNA and mRNA microarray experiments were performed and analyzed with bioinformatical tools, including Ingenuity Pathway Analysis (IPA). Principal component analysis showed a clear separation in both miRNA and mRNA expression levels between both ages studied, demonstrating strong age-related changes in expression. At the miRNA level, IPA identified differences between SHR and WKY related to metabolic diseases, cellular growth, and proliferation. The mRNAs differentially expressed between SHR and WKY were related to metabolism, cellular movement and proliferation. The most strongly upregulated gene (9.2-fold) was thrombospondin 4 (Thbs4), a protein involved in the endoplasmic reticulum (ER) stress response that activates transcription factor 6alpha (ATF6alpha). ATF6alpha downstream targets were also differentially expressed in SHR vs. WKY. Differential expression of THBS4, the cleaved form of ATF6alpha, and two of its targets were further confirmed at the protein level by western blot. In summary, these data revealed a number of genes (n = 202) and miRNAs (n = 3) in mesenteric arteries of SHR that had not been related to hypertension previously. The most prominent of these, Thbs4, is related to vascular ER stress that is associated with hypertension. PMID- 26356735 TI - Methods in HPV Surveillance: Experiences from a Population-Based Study of HPV Infection among Women in the San Juan Metropolitan Area of Puerto Rico. AB - This article describes the methodology of the first population-based study of human papillomavirus (HPV) infection among women aged 16-64 years residing in the San Juan Metropolitan Area of Puerto Rico (PR). The sample was identified through a complex sampling design of households. The sampling frame was selected in four stages, using census tracts maps from the Census Bureau. Women completed a face to-face interview and a computer-assisted self-interview using the Audio CASI system, for the collection of demographic, clinical, and lifestyle variables, and sampling acceptability. Anal, cervical, and oral specimens were collected through self-collection methods for HPV DNA testing using a modified pool of MY09/MY11 consensus HPV L1 and human beta-globin amplification primers. Anthropometric measurements were taken using the Third National Health and Nutrition Examination Survey methodology. Blood samples were collected to create a bio-repository for future HPV-related studies. Fifty census tract blocks were randomly selected. We recruited 566 women, with a response rate of 83.4%. Response rates did not vary by age-group (p>0.05); although they varied by socioeconomic (SES) census block stratums (p<0.05), response rates were good (>75%) in all SES strata. All participants agreed to respond to the surveys and provide the requested anogenital and oral samples. Overall, more than 98% understood and more than 50% felt comfortable with the cervical, anal, and oral self-collection methods used. This article documents the feasibility of performing population-based studies for HPV surveillance in women in PR. PMID- 26356737 TI - Knowledge of Case Workers and Correctional Officers towards HIV and HCV Infections: Opportunity for Public Health Education in the Correctional System. AB - OBJECTIVE: Given the heavy burden of hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections in correctional facilities, we examined knowledge about these infections among case workers and correctional officers in penal institutions in Puerto Rico. METHODS: We used data from a cross-sectional study of state prisons, commissioned by the Puerto Rico Department of Correction and Rehabilitation, to assess knowledge about HCV and HIV (10 items each) among 256 case workers and correctional officers from 18 penal institutions selected in the prison system. Total scores for each scale ranged from 0 to 10 points, with higher scores reflecting more knowledge. RESULTS: Of 256 participants, 64.8% were males, 39.6% were aged 30-39 years, and 70.3% were case workers. The percentage of correct responses for knowledge items ranged from 8.5% to 97.0% for HCV infection and from 38.7% to 99.6% for HIV infection. The vast majority (>96%) of participants knew that injection drug users should be tested for HCV infection and that sharing of needle injection equipment and multiple sex partners increase the risk of HIV infection. However, misconceptions about routes of transmission for these viral infections were found, with larger gaps in knowledge for HCV infection. Mean knowledge scores for HCV and HIV infections were 4.20+/-0.17 and 6.95+/-0.22, respectively, being significantly (p<0.05) higher for case workers. CONCLUSION: The findings about HCV and HIV knowledge in an important segment of the correctional system staff support the urgent need for increasing educational opportunities for correctional staff. PMID- 26356736 TI - Prevalence and Correlates of Penile HPV Infection in a Clinic-Based Sample of Hispanic Males. AB - OBJECTIVE: The aim of this manuscript is to describe the prevalence, genotypic distribution of penile HPV infection and the behavioral risk factors associated with penile HPV infection (any HPV type, high-oncogenic-risk [HR] types, low oncogenic-risk [LR] types, and of multiple HPV types) in a group of sexually active males who went to an STI clinic in San Juan, Puerto Rico. METHODS: After providing informed consent, the participants, underwent a detailed behavioral interview and a clinical examination. Frequency distributions and descriptive statistics were used to characterize the study samples. Prevalence estimates and 95% confidence intervals (CI) were calculated for any type of HPV, HR types, LR types, or multiple types. Logistic regression analyses was performed to determine factors associated with each of the HPV types. RESULTS: Two hundred and six participants were enrolled in this study. The mean age of the participants was 37.8+/-13.1 years. Close to 80% of the sample were infected with at least one HPV type; 73.5% were infected with one or more LR-HPV types; 32.4%, with one or more HR-HPV types; and 46.0%, with multiple HPV types. The most prevalent HR types were HPV-35, -31, and -16; the most prevalent LR types were HPV 6/11, and -84. After adjusting for age, having a high number of lifetime female sexual partners was highly associated with having multiple types of HPV infection (estimated OR=2.86; 95% CI=1.41, 5.80). CONCLUSION: HPV infection is common among sexually active males frequenting this STI clinic. HPV types not covered by the current quadrivalent HPV vaccine were identified. Multiple HPV types in the penis are significantly related to the lifetime number of female sexual partners. The high prevalence of HPV at this particular STI clinic evidences that males need to be targeted in primary care settings if the available vaccine is to be effectively promoted. In addition, opportunities for secondary prevention of HPV in STI settings are recommended, because of the burden of anal and penile cancer documented in the island. PMID- 26356738 TI - Are the University Hospitals in Puerto Rico following Current Guidelines for Cervical Cancer Screening? AB - OBJECTIVE: Cervical cancer is the fifth most common cancer among women in Puerto Rico (PR). Information about which obstetricians and gynecologists in PR are following current cervical cytology guidelines is not available. Our two objectives were to determine whether current guidelines for abnormal cervical cytology management were being followed adequately by OB-GYN residents and faculty at 3 university hospitals and, in addition, to evaluate the knowledge of the current guidelines that is possessed by these individuals. METHODS: A retrospective medical record review (records from January 2009 through December 2010) of patients with abnormal cervical cytology results (n=166) to evaluate the management they were given and a cross-sectional survey of OB-GYN residents (n=34) and faculty (n=46) to evaluate their knowledge of cervical cytology guidelines were both performed. RESULTS: One hundred and sixty-six medical records were reviewed. The level of management for 45% of the patients was found to have been optimal."Thirty-three percent were lost to follow-up. Eleven percent of the patients were managed sub optimally and the management of 12% of the patients was considered to have been poor. The survey showed that the faculty were less updated with regard to current guidelines for the management of cervical cytology than were the residents. Study limitations were the lack of electronic medical records in the hospital--which makes access to patient information more difficult--and the low response rate of the faculty. CONCLUSION: OB-GYN physicians and residents were not consistent with their management, according to current guidelines, of cervical cytological abnormalities. The high risk nature of the patients and their poor adherence to treatment (loss to follow up) may have been the cause of this inconsistency. Meetings aimed at addressing the lack of compliance by local OB-GYN physicians with the guidelines for cervical cancer screening have been Better screening strategies are also needed if we are to improve patient compliance in our population. PMID- 26356739 TI - Late HIV Testing in a Cohort of HIV-Infected Patients in Puerto Rico. AB - OBJECTIVE: Late HIV testing (LT), defined as receiving an AIDS diagnosis within a year of one's first positive HIV test, is associated with higher HIV transmission, lower HAART effectiveness, and worse outcomes. Latinos represent 36% of LT in the US, yet research concerning LT among HIV cases in Puerto Rico is scarce. METHODS: Multivariable logistic regression analysis was used to identify factors associated with LT, and a Cochran-Armitage test was used to determine LT trends in an HIV-infected cohort followed at a clinic in Puerto Rico specialized in the management and treatment of HIV. RESULTS: From 2000 to 2011, 47% of eligible patients were late testers, with lower median CD4 counts (54 vs. 420 cells/mm3) and higher median HIV viral load counts (253,680 vs. 23,700 copies/mL) than non-LT patients. LT prevalence decreased significantly, from 47% in 2000 to 37% in 2011. In a mutually adjusted logistic regression model, males, older age at enrollment and past history of IDU significantly increased LT odds, whereas having a history of amphetamine use decreased LT odds. When the data were stratified by mode of transmission, it became apparent that only the category men who have sex with men (MSM) saw a significant reduction in the proportion of LT, falling from 67% in 2000 to 33% in 2011. CONCLUSION: These results suggest a gap in early HIV detection in Puerto Rico, a gap that decreased only among MSM. An evaluation of the manner in which current HIV-testing guidelines are implemented on the island is needed. PMID- 26356740 TI - Left Ventricular Function Parameters in a Hispanic Population: Comparison of Planar & Tomographic Radionuclide Ventriculography (MUGA). AB - OBJECTIVE: Left ventricular (LV) function parameters have major diagnostic and prognostic importance in heart disease. Measurement of ventricular function with tomographic (SPECT) radionuclide ventriculography (MUGA) decreases camera time, improves contrast resolution, accuracy of interpretation and the overall reliability of the study as compared to planar MUGA. The relationship between these techniques is well established particularly with LV ejection fraction (LVEF), while there is limited data comparing the diastolic function parameters. Our goal was to validate the LV function parameters in our Hispanic population. METHODS: Studies from 44 patients, available from 2009-2010, were retrospectively evaluated. RESULTS: LVEF showed a good correlation between the techniques (r=0.94) with an average difference of 3.8%. In terms of categorizing the results as normal or abnormal, this remained unchanged in 95% of the cases (p=0.035). For the peak filling rate, there was a moderate correlation between the techniques (r=0.71), whereas the diagnosis remained unchanged in 89% of cases (p=0.0004). Time to peak filling values only demonstrated a weak correlation (r=0.22). Nevertheless, the diagnosis remained the same in 68% of the cases (p=0.089). CONCLUSION: Systolic function results in our study were well below the 7-10% difference reported in the literature. Only a weak to moderate correlation was observed with the diastolic function parameters. Comparison with echocardiogram (not available) may be of benefit to evaluate which of these techniques results in more accurate diastolic function parameters. PMID- 26356741 TI - Experience with Percutaneous Transcatheter Closure of Interatrial Communications at the Cardiovascular Center of Puerto Rico and the Caribbean. AB - OBJECTIVE: The annual rate of percutaneous transcatheter closure of atrial septal defects (ASDs) and patent foramen ovales (PFO) has markedly increased in the United States over the past decade. This technique has been used at the Cardiovascular Center for Puerto Rico and the Caribbean since 2005. We report on the clinical characteristics and the immediate and short-term follow-up of adult patients who underwent this procedure at this center from 2008 to 2012. METHODS: One hundred and two consecutive medical records of adult Hispanic patients who underwent this procedure at our center from 2008 to 2012 were identified. A retrospective analysis of the clinical characteristics and the immediate and short-term clinical and echocardiographic follow-up of those patients was performed. RESULTS: The study population comprised 70 women and 32 men, with a mean age of 51 years (age range: 19 to 80 years). Of those, 43 (42%) underwent ASD closure and 60 (59%), closure of a PFO. A 99% procedural success rate was achieved. There were only 3 procedural complications, including the failure of the initial implantation of 1 device, which required the endovascular removal of that device and the implantation of another, a hematoma at the vascular access site, and 1 brief episode of atrial fibrillation. CONCLUSION: Based on our review of the available records, we were able to determine that the percutaneous transcatheter closure of interatrial communications proved to be, at our institution, a safe procedure with a high success rate and a low incidence of in hospital complications. To our knowledge, this is the first report on the utilization of this interventional procedure in Puerto Rico. PMID- 26356742 TI - Impact of Day of the Week and Time of Arrival on Ischemic Stroke Management. AB - OBJECTIVE: The purpose of this study was to evaluate the association between measures of patient arrival day (weekday or weekend day), day part (nighttime vs. daytime) and hour (regular hours vs. off hours) at the stroke unit of the Emergency Department of the Puerto Rico Medical Center and the following time-to treatment measures: door-to-CT-scan, door-to-needle, and stroke-onset-to treatment. METHODS: In this retrospective study, the data of 54 patients was obtained from the stroke unit of the Puerto Rico Medical Center through the Get With The Guidelines- Stroke Registry. Inclusion criteria were as follows: having an ischemic stroke within the period covering from August 2008 through February 2010 and being at least 18 years old. Associations between patient arrival time and timeliness of interventions were assessed using t-tests/Mann-Whitney tests and chi-square tests/Fisher's exact tests, as appropriate. RESULTS: The majority of the patients (74%) were men. The mean and standard deviation of age was 67+/ 14 years. The median of times for door-to-CT-scan and onset to treatment were 15 minutes (interquartile range=15) and 2.7 hours (interquartile range=0.6), respectively. The mean and standard deviation for door-to-needle time was 77+/-18 minutes. No differences were found for any of the variables in terms of arrival date, day part or hour (p>0.05). The median time for door-to-CT- scan was shorter for patients receiving intravenous tissue plasminogen activator treatment than it was for those not receiving such treatment (12 minutes vs. 20 minutes; p=0.02). CONCLUSION: The timeliness of the stroke management interventions did not differ significantly in terms of arrival day, day part, or hour. PMID- 26356743 TI - A Case of Fenofibrate-Induced Immune Thrombocytopenia: First Report. AB - Fenofibrate is widely prescribed as a hypolipidemic drug and is well tolerated by most patients. We present the case of a 40-year-old woman who developed severe immune thrombocytopenia while on fenofibrate treatment. Clinical features included spontaneous bruising on the feet and hands, a purpuric rash, and menorrhagia. All the laboratory results were normal except for the finding of isolated thrombocytopenia. The subsequent evolution was favorable after fenofibrate removal and with the administration of immunoglobulin G (IgG) plus corticosteroids. Drug-induced thrombocytopenia is briefly reviewed, and a possible mechanism responsible for causing this side effect of fenofibrate is suggested. This is the first reported case of fenofibrate-induced immune thrombocytopenia. PMID- 26356744 TI - Does Interaction between the Motor and Regulatory Domains of the Myosin Head Occur during ATPase Cycle? Evidence from Thermal Unfolding Studies on Myosin Subfragment 1. AB - Myosin head (myosin subfragment 1, S1) consists of two major structural domains, the motor (or catalytic) domain and the regulatory domain. Functioning of the myosin head as a molecular motor is believed to involve a rotation of the regulatory domain (lever arm) relative to the motor domain during the ATPase cycle. According to predictions, this rotation can be accompanied by an interaction between the motor domain and the C-terminus of the essential light chain (ELC) associated with the regulatory domain. To check this assumption, we applied differential scanning calorimetry (DSC) combined with temperature dependences of fluorescence to study changes in thermal unfolding and the domain structure of S1, which occur upon formation of the ternary complexes S1-ADP-AlF4- and S1-ADP-BeFx that mimic S1 ATPase intermediate states S1**-ADP-Pi and S1*-ATP, respectively. To identify the thermal transitions on the DSC profiles (i.e. to assign them to the structural domains of S1), we compared the DSC data with temperature-induced changes in fluorescence of either tryptophan residues, located only in the motor domain, or recombinant ELC mutants (light chain 1 isoform), which were first fluorescently labeled at different positions in their C-terminal half and then introduced into the S1 regulatory domain. We show that formation of the ternary complexes S1-ADP-AlF4- and S1-ADP-BeFx significantly stabilizes not only the motor domain, but also the regulatory domain of the S1 molecule implying interdomain interaction via ELC. This is consistent with the previously proposed concepts and also adds some new interesting details to the molecular mechanism of the myosin ATPase cycle. PMID- 26356745 TI - Evolution of a Novel Antiviral Immune-Signaling Interaction by Partial-Gene Duplication. AB - The RIG-like receptors (RLRs) are related proteins that identify viral RNA in the cytoplasm and activate cellular immune responses, primarily through direct protein-protein interactions with the signal transducer, IPS1. Although it has been well established that the RLRs, RIG-I and MDA5, activate IPS1 through binding between the twin caspase activation and recruitment domains (CARDs) on the RLR and a homologous CARD on IPS1, it is less clear which specific RLR CARD(s) are required for this interaction, and almost nothing is known about how the RLR-IPS1 interaction evolved. In contrast to what has been observed in the presence of immune-modulating K63-linked polyubiquitin, here we show that-in the absence of ubiquitin-it is the first CARD domain of human RIG-I and MDA5 (CARD1) that binds directly to IPS1 CARD, and not the second (CARD2). Although the RLRs originated in the earliest animals, both the IPS1 gene and the twin-CARD domain architecture of RIG-I and MDA5 arose much later in the deuterostome lineage, probably through a series of tandem partial-gene duplication events facilitated by tight clustering of RLRs and IPS1 in the ancestral deuterostome genome. Functional differentiation of RIG-I CARD1 and CARD2 appears to have occurred early during this proliferation of RLR and related CARDs, potentially driven by adaptive coevolution between RIG-I CARD domains and IPS1 CARD. However, functional differentiation of MDA5 CARD1 and CARD2 occurred later. These results fit a general model in which duplications of protein-protein interaction domains into novel gene contexts could facilitate the expansion of signaling networks and suggest a potentially important role for functionally-linked gene clusters in generating novel immune-signaling pathways. PMID- 26356746 TI - Tetramic Acids and Pyridone Alkaloids from the Endolichenic Fungus Tolypocladium cylindrosporum. AB - Three new tetramic acid derivatives, tolypocladenols A1, A2, and B (1-3), a new pyridone alkaloid, tolypyridone A (4), and a new coumarin derivative, 3,8 dihydroxy-4-(4-hydroxyphenyl)-6-methylcoumarin (5), together with four known compounds (6-9) were isolated from the endolichenic fungus Tolypocladium cylindrosporum, which inhabits the lichen Lethariella zahlbruckneri. Structures of these compounds were determined by comprehensive analysis of spectroscopic data and single-crystal X-ray diffraction determination. Bioassay of the isolated compounds found that pyridoxatin (7) was cytotoxic to human cancer cells by induction of G0/G1 cell cycle arrest and apoptosis. PMID- 26356747 TI - Identifying Septal Support Reconstructions for Saddle Nose Deformity: The Cakmak Algorithm. AB - IMPORTANCE: The saddle nose deformity is one of the most challenging problems in nasal surgery with a less predictable and reproducible result than other nasal procedures. The main feature of this deformity is loss of septal support with both functional and aesthetic implications. Most reports on saddle nose have focused on aesthetic improvement and neglected the reestablishment of septal support to improve airway. OBJECTIVES: To explain how the Cakmak algorithm, an algorithm that describes various fixation techniques and grafts in different types of saddle nose deformities, aids in identifying saddle nose reconstructions that restore supportive nasal framework and provide the aesthetic improvements typically associated with procedures to correct saddle nose deformities. DESIGN, SETTING, AND PARTICIPANTS: This algorithm presents septal support reconstruction of patients with saddle nose deformity based on the experience of the senior author in 206 patients with saddle nose deformity. Preoperative examination, intraoperative assessment, reconstruction techniques, graft materials, and patient evaluation of aesthetic success were documented, and 4 different types of saddle nose deformities were defined. MAIN OUTCOMES AND MEASURES: The Cakmak algorithm classifies varying degrees of saddle nose deformity from type 0 to type 4 and helps identify the most appropriate surgical procedure to restore the supportive nasal framework and aesthetic dorsum. RESULTS: Among the 206 patients, 110 women and 96 men, mean (range) age was 39.7 years (15-68 years), and mean (range) of follow-up was 32 months (6-148 months). All but 12 patients had a history of previous nasal surgeries. Application of the Cakmak algorithm resulted in 36 patients categorized with type 0 saddle nose deformities; 79, type 1; 50, type 2; 20, type 3a; 7, type 3b; and 14, type 4. Postoperative photographs showed improvement of deformities, and patient surveys revealed aesthetic improvement in 201 patients and improvement in nasal breathing in 195 patients. Three patients developed postoperative infection and 21 patients underwent revision septal surgery. CONCLUSIONS AND RELEVANCE: The goal of saddle nose reconstruction should be not only to restore an aesthetic dorsum but also to restore the supportive nasal framework. The surgeon should provide more projected and strengthened septal support before augmentation of saddle nose deformity to improve breathing and achieve a stable long-term result. The Cakmak algorithm is a mechanism that helps surgeons identify the most effective way to maximize septal support and aesthetic appeal. LEVEL OF EVIDENCE: 4. PMID- 26356748 TI - Comparison of Early Surgical Experience and Visual Outcomes of DSAEK and DMEK. AB - PURPOSE: To compare the outcomes of 2 different endothelial keratoplasty (EK) techniques [Descemet stripping automated endothelial keratoplasty (DSAEK) and Descemet membrane endothelial keratoplasty (DMEK)] sequentially learned by a corneal fellow. METHODS: This is a retrospective comparative audit of all patients undergoing EK by 1 surgeon (M.G.) during fellowship. Surgical and functional success of both procedures were compared. Surgical success was evaluated by comparing short-term complications, and functional success by comparing visual outcomes in patients with Fuchs endothelial dystrophy (FED). RESULTS: Twenty-six patients were included in the review (DSAEK 12 and DMEK 14). Phacoemulsification was combined with EK in 14 patients (DSAEK 6 and DMEK 8). The average follow-up duration was 3.5 months. Partial detachment requiring rebubbling was slightly more common in the DMEK group (DSAEK 1 and DMEK 5); total detachment requiring repositioning was less in the DMEK group (DSAEK 2 and DMEK 1). Only 1 patient experienced primary graft failure due to complicated graft insertion, and this patient underwent DMEK. Functional analysis included 14 patients with FED (DSAEK 7 patients, preoperative 6/18, postoperative 6/12; DMEK 7 patients, preoperative 6/12, postoperative 6/6). Average visual improvement was greater in the DMEK group (3.3 lines) than in the DSAEK group (1.3 lines; P = 0.047). In DMEK patients, the average postoperative endothelial cell count was 1612 cells per square centimeter. CONCLUSIONS: Contrary to common expectation, there were similar rates of surgical success while learning DMEK and DSAEK. Visual improvement in patients with FED undergoing DMEK was significantly better at this early point of comparison. PMID- 26356749 TI - Retrospective Analysis Comparing the Preoperative and Postoperative "Q" Values for 2 Different Lasers in Refractive Surgery. AB - PURPOSE: To compare the presurgical and postsurgical corneal asphericity, or "Q value," between VISX Wavefront-guided treatment and Allegretto Wave Wavefront optimized treatment in photorefractive keratectomy for the correction of myopia. METHODS: This is a retrospective database analysis performed at the Joint Warfighter Refractive Surgery Center, Lackland Air Force Base, TX. All data were accessed through the Institutional Review Board-approved Joint Warfighter Refractive Surgery Center database. Fifty-one patient records (102 eyes) were reviewed to determine the change in the Q value after photorefractive keratectomy for the correction of myopia. RESULTS: The average change in the Q value per diopter of treatment sphere over the entire study population was 0.12 (+/-0.04) for Allegretto and 0.14 (+/-0.04) for VISX (P = 0.004). There was no statistical difference among the preoperative and postoperative best-corrected visual acuities (BCVAs), low-contrast BCVA (BCVA 5%), or quality of vision complaints between both platforms. CONCLUSIONS: Low to moderate myopic correction with the Allegretto laser was associated with a smaller change in the Q value per diopter of treatment and therefore more closely maintained the original prolate shape of the cornea when compared with VISX. No difference in the postoperative visual outcome between both groups was detected. PMID- 26356750 TI - Sequential Intracorneal Ring Segment Implantation and Corneal Transepithelial Collagen Cross-Linking in Keratoconus. AB - PURPOSE: To assess the clinical outcomes after sequential surgical implantation of intracorneal ring segments and transepithelial corneal collagen cross-linking (TE-CXL) in keratoconic eyes. METHODS: In this consecutive randomized study, 40 eyes of 29 patients with progressive mild to moderate keratoconus were included and were randomly divided into two groups. Group 1 included 20 eyes that underwent Keraring implantation, and group 2 included 20 eyes that underwent Keraring insertion followed by TE-CXL 1 month later. In both groups, channel creation was performed manually. Visual, refractive, and topographic outcomes were measured preoperatively and 1, 3, and 6 months postoperatively. RESULTS: There was statistically significant improvement in both groups regarding uncorrected distance visual acuity (P < 0.001) and corrected distance visual acuity (P < 0.001), with a significant reduction in the refractive error and keratometric values (P < 0.001). There was no statistically significant difference between both groups regarding changes in uncorrected distance visual acuity, corrected distance visual acuity, and refractive error (P > 0.05). However, group 2 revealed a more statistically significant reduction in spherical refraction after 3 months (P = 0.04) and highly significant improvement after 6 months (P = 0.004). CONCLUSIONS: Intracorneal ring segment implantation is an effective procedure for visual and refractive improvement in keratoconic eyes. The addition of TE-CXL to the procedure compensates for residual superficial irregularities, disrupts the progression of the disease, and provides greater improvements in spherical values. The process is simply a deep stretch with superficial lamellar stiffness. PMID- 26356751 TI - Screening for Keratoconus With New Dynamic Biomechanical In Vivo Scheimpflug Analyses. AB - PURPOSE: To improve keratoconus (KC) screening with new in vivo biomechanical Scheimpflug analyses. METHODS: After adjusting for intraocular pressure and corneal thickness, predefined static and new dynamic Scheimpflug curve analyses [Pentacam HR and Corvis ST (CST); Oculus] of 87 normal eyes, 27 subclinical KC eyes, 42 suspected KC, and 65 manifest KC eyes were reviewed retrospectively. A t test (for a normal distribution), Wilcoxon matched-pairs test (if not normally distributed), and receiver operating characteristics were used to test for statistically significant differences between these groups. In addition, new dynamic curve analyses were performed to analyze corneal dynamics throughout the entire response to the CST air puff impulse. RESULTS: Comparing normal and KC suspect eyes, the parameters A1 length, A2 length, radius of the inward-bended cornea, and deflection length at the highest concavity revealed statistically significant differences. In addition, the newly calculated "applanation length level" and "deflection length level" demonstrated consistently increasing differences with increasing statistical significance between normal eyes and those with advancing KC stages. However, when comparing normal and subclinical KC eyes, none of the analyzed parameters demonstrated statistically significant differences. CONCLUSIONS: In vivo biomechanical analyses (CST) at their current state only marginally improve KC screening protocols. Newly generated parameters such as the applanation length level and deflection length level might further improve early KC screening. PMID- 26356752 TI - Accelerated (18 mW/cm2) Corneal Collagen Cross-Linking for Progressive Keratoconus. AB - PURPOSE: The aim of this study was to determine the efficacy of accelerated riboflavin-ultraviolet A-induced corneal collagen cross-linking (CXL) (irradiance of 18 mW/cm2 for 5 minutes). METHODS: In this study, we retrospectively reviewed the charts and anterior segment data of patients after accelerated CXL. Visual, topographic, pachymetry, and densitometry data were extracted and analyzed before surgery and at follow-up (minimum 12 months) after treatment. RESULTS: A total of 28 eyes of 20 patients (mean age, 28.1 +/- 8.1 years) were included in this study. The mean follow-up time was 21.7 +/- 7.2 months (range, 12-34 months). No statistically significant changes were found in the mean corrected distance visual acuity, corneal astigmatism, Kmean, Kflat, Ksteep, corneal pachymetry (at the apex and at the thinnest point), and corneal densitometry at follow-up. A significant reduction of Kmax, index of surface variance, index of vertical asymmetry, and Km of the posterior corneal surface (Km(B)) was observed (Kmax: P = 0.018; index of surface variance: P = 0.016; index of vertical asymmetry: P = 0.038; Km(B): P = 0.008). No complications were reported during the postoperative follow-up period in this study. CONCLUSIONS: Based on a mean follow-up time of 21.7 months, accelerated CXL (18 mW/cm; 5 minutes) is effective in stopping the progression of keratoconus without raising any safety concerns. Improvement in Kmax and stabilization of corrected distance visual acuity were noted after treatment. However, prospective studies with longer follow-up using different accelerated CXL settings are needed to validate these findings. PMID- 26356753 TI - "Copy and Fix": A New Technique of Harvesting Freehand and Horseshoe Tectonic Grafts. AB - PURPOSE: To describe a new technique for harvesting freehand and horseshoe tectonic corneal grafts. METHODS: A retrospective, noncomparative interventional case series of 3 eyes from 2 patients was included. The area to be excised from the host was marked with a marking pen. Using the principle of the light table from architecture, the donor corneoscleral rim was placed over the marked area with an ophthalmic viscoelastic device in the interface to provide a coupling medium. The donor was then marked, tracing the exact shape of the tectonic graft with a 0.2-mm overlap ("copy"). This was harvested after mounting on an artificial anterior chamber and sutured in place with 10-0 nylon ("fix") to provide an exact copy of the eccentric or horseshoe shape of the tectonic graft. One eye had a full-thickness freehand tectonic corneal graft for perforated microbial keratitis too large to glue. Two eyes from the same patient had anterior lamellar horseshoe tectonic grafts for Terrien marginal degeneration. RESULTS: None of the grafts required any modification in their dimensions after harvesting. All grafts were easy to perform and tectonically stable postoperatively. A significant visual improvement was observed in all cases. CONCLUSIONS: The "copy and fix" technique is a simple and effective new technique that consistently and accurately maps and harvests freehand and horseshoe tectonic corneal grafts. PMID- 26356754 TI - Topical Valganciclovir for the Treatment of Hypertensive Anterior Uveitis. AB - PURPOSE: To report the use of topical valganciclovir for the treatment of hypertensive anterior uveitis associated with clinical signs of cytomegalovirus (CMV) iritis. METHODS: A case report and review of the literature. RESULTS: A 37 year-old man was referred with a unilateral hypertensive anterior uveitis with keratic precipitates suggestive of CMV as the causative agent. After institution of oral valganciclovir and topical corticosteroids, the patient's ocular inflammation resolved and intraocular pressure normalized. Therapy was eventually changed from oral valganciclovir to ophthalmic 1% valganciclovir ointment, which was able to effectively control ocular inflammation and allow the patient to discontinue topical corticosteroids and antihypertensive medications. Topical application of valganciclovir did not result in clinically evident ocular surface toxicity. CONCLUSIONS: 1% valganciclovir ointment may prove to be an effective treatment of hypertensive anterior uveitis associated with clinical signs of CMV iritis. PMID- 26356755 TI - Serologic Markers Are Associated With Ocular Staining Score in Primary Sjogren Syndrome. AB - PURPOSE: To investigate the relationship between serologic markers and dry eye severity in subjects with primary Sjogren syndrome (SS). METHODS: This study evaluated 64 patients diagnosed with primary SS according to the 2012 Sjogren's International Collaborative Clinical Alliance (SICCA) classification criteria. Serum anti-Ro/SSA, anti-La/SSB, rheumatoid factor (RF), and antinuclear antibody (ANA) levels, Ocular Surface Disease Index (OSDI), Schirmer I test values, tear film breakup time, and SICCA ocular staining score (OSS) were determined. RESULTS: The conjunctival staining scores were 3.3 +/- 1.9, 3.6 +/- 2.0, 3.4 +/- 1.9, and 3.5 +/- 1.9 in the positive anti-Ro (>=25 EU), positive anti-La (>=25 EU), positive RF (>=20 IU/mL), and positive ANA (>=1:320) group, respectively. Subjects with positive anti-Ro, anti-La, RF, or ANA had significantly higher conjunctival staining scores compared with those with negative levels (P < 0.05). The total OSS in the positive ANA group was 5.5 +/- 3.0, which was significantly higher than the total OSS (3.4 +/- 2.1) in the negative ANA group (P = 0.005). Serum RF and ANA levels had strong correlations with conjunctival staining scores and the total OSS but not with corneal staining scores (r = 0.53, P < 0.001 and r = 0.382, P = 0.002). Other ocular parameters (OSDI, Schirmer I test values, and tear film breakup time) did not differ by the serologic marker level. Interestingly, the OSDI was positively correlated with the corneal staining score and total OSS (r = 0.646, P < 0.001 and r = 0.476, P < 0.001). CONCLUSIONS: Serum RF and ANA levels are associated with conjunctival staining scores and the total OSS according to the SICCA OSS in primary SS. PMID- 26356756 TI - Postoperative Graft Thickness Obtained With Single-Pass Microkeratome-Assisted Ultrathin Descemet Stripping Automated Endothelial Keratoplasty. AB - PURPOSE: To evaluate the results of microkeratome-assisted ultrathin Descemet stripping automated endothelial keratoplasty (UT-DSAEK) using a nomogram developed for the single-pass technique. METHODS: A retrospective study of eyes operated between September 2014 and March 2015 at Villa Serena-Villa Igea Private Hospitals (Forli, Italy) by a single surgeon (M.B.). Study eyes underwent UT DSAEK performed using a linear microkeratome-assisted lamellar dissection with disposable heads of different sizes (Moria ALTK system; Moria SA) chosen according to a pachymetry-based nomogram developed at our department. The main outcome measure was the graft thickness as assessed by means of anterior segment optical coherence tomography, measured between 1 and 3 months postoperatively. RESULTS: Forty-two eyes were included in this study. Mean follow-up time was 5.0 +/- 1.8 months (range 1.2-6.9 months). No perforation or other complication occurred during graft preparation. Mean postoperative central thickness of donor grafts was 63 +/- 29 MUm. Thickness ranged between 23 and 177 MUm, and the second thickest graft measured 116 MUm. By 3 months postoperatively, 41/42 (97%) of the grafts were of thickness <=130 MUm and 38/42 (90%) of the grafts were of central thickness <=100 MUm. The mean nasal-to-temporal absolute thickness difference at the graft's central 3-mm zone was 5 +/- 7 MUm at the last available measurement. CONCLUSIONS: The nomogram developed at our institution allowed reliable single pass microkeratome-assisted dissection of donor tissue, creating consistently thin and symmetric grafts without loss of tissue. The results obtained compare favorably with those reported in the past for double-pass microkeratome-assisted dissection of UT-DSAEK. PMID- 26356760 TI - Connectivity mapping using a combined gene signature from multiple colorectal cancer datasets identified candidate drugs including existing chemotherapies. AB - BACKGROUND: While the discovery of new drugs is a complex, lengthy and costly process, identifying new uses for existing drugs is a cost-effective approach to therapeutic discovery. Connectivity mapping integrates gene expression profiling with advanced algorithms to connect genes, diseases and small molecule compounds and has been applied in a large number of studies to identify potential drugs, particularly to facilitate drug repurposing. Colorectal cancer (CRC) is a commonly diagnosed cancer with high mortality rates, presenting a worldwide health problem. With the advancement of high throughput omics technologies, a number of large scale gene expression profiling studies have been conducted on CRCs, providing multiple datasets in gene expression data repositories. In this work, we systematically apply gene expression connectivity mapping to multiple CRC datasets to identify candidate therapeutics to this disease. RESULTS: We developed a robust method to compile a combined gene signature for colorectal cancer across multiple datasets. Connectivity mapping analysis with this signature of 148 genes identified 10 candidate compounds, including irinotecan and etoposide, which are chemotherapy drugs currently used to treat CRCs. These results indicate that we have discovered high quality connections between the CRC disease state and the candidate compounds, and that the gene signature we created may be used as a potential therapeutic target in treating the disease. The method we proposed is highly effective in generating quality gene signature through multiple datasets; the publication of the combined CRC gene signature and the list of candidate compounds from this work will benefit both cancer and systems biology research communities for further development and investigations. PMID- 26356761 TI - Icaritin inhibits the invasion and epithelial-to-mesenchymal transition of glioblastoma cells by targeting EMMPRIN via PTEN/AKt/HIF-1alpha signalling. AB - Icaritin, a hydrolytic product of icariin from the Epimedium genus, exerts anti tumour effects on a variety of tumour cell types, mainly by inhibiting cell proliferation and inducing apoptosis. However, little is known about the role of icaritin in cancer invasion and epithelial-to-mesenchymal transition (EMT). In the present study, the glioblastoma (GBM) cell line U87MG was used as a model to investigate the effects of icaritin on the invasion and EMT of cancer cells. The results showed that icaritin significantly inhibited the invasion and EMT of GBM cells by targeting extracellular matrix metalloproteinase (EMMPRIN). Furthermore, the findings strongly indicate that the modulatory effect of icaritin on EMMPRIN is mediated via the PTEN/Akt/HIF-1alpha signalling pathway. The data provide the first experimental evidence of the inhibitory effect of icaritin on cancer cell invasion and EMT, thus highlighting the potential of icaritin to be employed as a promising anti-cancer agent in the treatment of GBM. PMID- 26356762 TI - Microwave-accelerated bioassay technique for rapid and quantitative detection of biological and environmental samples. AB - Quantitative detection of molecules of interest from biological and environmental samples in a rapid manner, particularly with a relevant concentration range, is imperative to the timely assessment of human diseases and environmental issues. In this work, we employed the microwave-accelerated bioassay (MAB) technique, which is based on the combined use of circular bioassay platforms and microwave heating, for rapid and quantitative detection of Glial Fibrillary Acidic Protein (GFAP) and Shiga like toxin (STX 1). The proof-of-principle use of the MAB technique with the circular bioassay platforms for the rapid detection of GFAP in buffer based on colorimetric and fluorescence readouts was demonstrated with a 900W kitchen microwave. We also employed the MAB technique with a new microwave system (called the iCrystal system) for the detection of GFAP from mice with brain injuries and STX 1 from a city water stream. Control bioassays included the commercially available gold standard bioassay kits run at room temperature. Our results show that the lower limit of detection (LLOD) of the colorimetric and fluorescence based bioassays for GFAP was decreased by ~1000 times using the MAB technique and our circular bioassay platforms as compared to the commercially available bioassay kits. The overall bioassay time for GFAP and STX 1 was reduced from 4h using commercially available bioassay kits to 10min using the MAB technique. PMID- 26356763 TI - Smartphone based visual and quantitative assays on upconversional paper sensor. AB - The integration of smartphone with paper sensors recently has been gain increasing attentions because of the achievement of quantitative and rapid analysis. However, smartphone based upconversional paper sensors have been restricted by the lack of effective methods to acquire luminescence signals on test paper. Herein, by the virtue of 3D printing technology, we exploited an auxiliary reusable device, which orderly assembled a 980nm mini-laser, optical filter and mini-cavity together, for digitally imaging the luminescence variations on test paper and quantitative analyzing pesticide thiram by smartphone. In detail, copper ions decorated NaYF4:Yb/Tm upconversion nanoparticles were fixed onto filter paper to form test paper, and the blue luminescence on it would be quenched after additions of thiram through luminescence resonance energy transfer mechanism. These variations could be monitored by the smartphone camera, and then the blue channel intensities of obtained colored images were calculated to quantify amounts of thiram through a self-written Android program installed on the smartphone, offering a reliable and accurate detection limit of 0.1MUM for the system. This work provides an initial demonstration of integrating upconversion nanosensors with smartphone digital imaging for point-of-care analysis on a paper-based platform. PMID- 26356764 TI - Development of mercury (II) ion biosensors based on mercury-specific oligonucleotide probes. AB - Mercury (II) ion (Hg(2+)) contamination can be accumulated along the food chain and cause serious threat to the public health. Plenty of research effort thus has been devoted to the development of fast, sensitive and selective biosensors for monitoring Hg(2+). Thymine was demonstrated to specifically combine with Hg(2+) and form a thymine-Hg(2+)-thymine (T-Hg(2+)-T) structure, with binding constant even higher than T-A Watson-Crick pair in DNA duplex. Recently, various novel Hg(2+) biosensors have been developed based on T-rich Mercury-Specific Oligonucleotide (MSO) probes, and exhibited advanced selectivity and excellent sensitivity for Hg(2+) detection. In this review, we explained recent development of MSO-based Hg(2+) biosensors mainly in 3 groups: fluorescent biosensors, colorimetric biosensors and electrochemical biosensors. PMID- 26356765 TI - Human dilated ascending aorta: Mechanical characterization via uniaxial tensile tests. AB - Aneurysms of the ascending aorta (AsAA), i.e., a progressive and localized dilatation of the first part of the aorta, represent a severe life-threatening condition, often occurring with no symptom. AsAA formation is associated with a degeneration of the aortic wall tissue, which leads to changes in the tissue mechanical properties, and in particular to increased wall stress and/or decreased wall ultimate strength. Nowadays, the decision to surgically operate is usually based on the AsAA diameter, although such a criterion is not always predictive. The present study focuses on the mechanical characterization of the AsAA tissues. Specimens were cut from portions of dilated ascending aorta excised from 46 patients through open-heart surgery. Peak strain, peak stress, and maximum elastic modulus (i.e., tissue stiffness) were measured from uniaxial stress-strain curves. Such (ultimate) mechanical properties were collected for different regions of the aortic wall (anterior and posterior) as well as for different specimen orientations (circumferential and longitudinal). Relationships of ultimate mechanical properties with patient age and sex were also investigated. The obtained results highlighted a significant anisotropy of the AsAA tissue (as also observed for healthy aortic tissues), with higher value of strength and stiffness in the circumferential than in the longitudinal direction. Higher strength and stiffness were also found in the posterior region with respect to the anterior one for the circumferential orientation, whereas an opposite result was found for the longitudinal orientation. A decreasing trend of ultimate mechanical properties with aging was also highlighted. Finally, a significant difference in the strength between male and female was observed only in the circumferential direction. PMID- 26356767 TI - Editorial: LGBTQ families in the 21st Century. PMID- 26356766 TI - Monoterpene biosynthesis potential of plant subcellular compartments. AB - Subcellular monoterpene biosynthesis capacity based on local geranyl diphosphate (GDP) availability or locally boosted GDP production was determined for plastids, cytosol and mitochondria. A geraniol synthase (GES) was targeted to plastids, cytosol, or mitochondria. Transient expression in Nicotiana benthamiana indicated local GDP availability for each compartment but resulted in different product levels. A GDP synthase from Picea abies (PaGDPS1) was shown to boost GDP production. PaGDPS1 was also targeted to plastids, cytosol or mitochondria and PaGDPS1 and GES were coexpressed in all possible combinations. Geraniol and geraniol-derived products were analyzed by GC-MS and LC-MS, respectively. GES product levels were highest for plastid-targeted GES, followed by mitochondrial- and then cytosolic-targeted GES. For each compartment local boosting of GDP biosynthesis increased GES product levels. GDP exchange between compartments is not equal: while no GDP is exchanged from the cytosol to the plastids, 100% of GDP in mitochondria can be exchanged to plastids, while only 7% of GDP from plastids is available for mitochondria. This suggests a direct exchange mechanism for GDP between plastids and mitochondria. Cytosolic PaGDPS1 competes with plastidial GES activity, suggesting an effective drain of isopentenyl diphosphate from the plastids to the cytosol. PMID- 26356768 TI - Expanding the Therapy Paradigm with Queer Couples: A Relational Intersectional Lens. AB - North American and global cultures in general-and the field of Couple and Family Therapy in particular-have made significant strides toward recognizing and validating LGBTQ identities and relationships. However, clinical assessment and conceptualization of queer couples still lack the complexity needed to encompass the issues involved in treatment. Existing literature provides clinicians a basic understanding of queer couples and the dynamics that make them unique from nonqueer couples. However, much of this knowledge has been normed on White middle class couples and has rarely included couples with transgender or bisexual members. This article invites clinicians and researchers to apply a feminist model of intersectionality to understand queer couples. Our proposed intersectional lens considers multiple axes of identity and power and their interrelationships (Crenshaw, 1989, 1991). We argue that intersectionality is important for understanding all identities, whether privileged or marginalized (Falicov, 2003). This application of the concept of intersectionality is unique in its relational focus, emphasizing how partners' complex individual identities overlap with and intersect with one another. Additionally, this lens considers how the therapists' and clients' multidimensional identities intersect. Three case studies are presented to illustrate application of the intersectional lens. In each case, exploring the partners' multiple social locations, their influences on one another, and the therapist's intersections of identity all proved critical to the direction of therapy. PMID- 26356769 TI - Response to Letter to the Editor on COI for American Thyroid Association Statement on Surgical Application of Molecular Profiling for Thyroid Nodules. PMID- 26356770 TI - The influence of unstable modified wall squat exercises on the posture of female university students. AB - [Purpose] The purpose of this study was to examine the effect of unstable modified wall squat exercises on the posture of female university students. [Subjects] The subjects of this study were 30 female university students who were equally and randomly allocated to an unstable modified wall squat exercises group the experimental group and a stable modified wall squat exercises group the control group. [Methods] Both groups performed their respective exercises for 30 minutes three times per week over a six-week period. Using BackMapper, trunk inclination, trunk imbalance, pelvic position, pelvic torsion, pelvic rotation, and position of the scapulae were evaluated. [Results] The unstable modified wall squat exercises group obtained significant results for trunk inclination, trunk imbalance, pelvic position, pelvic torsion, position of the scapulae, while the stable modified wall squat exercises group obtained significant results for trunk imbalance and pelvic position. [Conclusion] Unstable modified wall squat exercises may be applied as a method to correct the posture of average adults. PMID- 26356771 TI - A Comparison of the Danish and the South Korean Health Care System. PMID- 26356772 TI - Celebrating the 75th anniversary of the American Journal of Psychoanalysis. PMID- 26356773 TI - Some psychoanalytic reflections on the concept of dignity. AB - After reviewing the pertinent philosophical and psychoanalytic writings on the concept of dignity, this paper proposes three categories of dignity. Conceptualized as phenomenological clusters, heuristic viewpoints, and levels of abstraction, these include (i) metaphysical dignity which extends the concept of dignity beyond the human species to all that exists in this world, (ii) existential dignity which applies to human beings alone and rests upon their inherent capacity for moral transcendence, and (iii) characterological dignity which applies more to some human beings than others since they possess a certain set of personality traits that are developmentally derived. The paper discusses the pros and cons of each category and acknowledges the limitations of such classification. It also discusses the multiple ways in which these concepts impact upon clinical work and concludes with some remarks on the relationship of dignity to choice, narcissism, and suicide. PMID- 26356774 TI - The Holocaust after 70 years: Holocaust survivors in the United States(.). AB - Over 70 years, there have been different narratives of the Holocaust survivors coming to the United States. Survivors' stories begin with an event of major historical significance. Difficulties in conceptualizing historical trauma, along with common distortions and myths about Holocaust survivors and their children are examined. This article proposes that it is impossible to discuss the consequences of extreme suffering without consideration of historical meaning and social context with which they are entwined. The evolution of the social representation of the Holocaust and the contradictions in clinical attributions to survivors and their children with consideration of the future is described. Attributions to survivors and their children with consideration of the future is described. PMID- 26356775 TI - Seeing double, being double: longing, belonging, recognition, and evasion in psychodynamic work with immigrants. AB - Psychically immigrants live double lives, simultaneously dwelling in the world they have left and the world in which they live, and into which most try to fit to avoid the alienating experience of being "other". Doubleness is not a conscious act, but it is a preconscious counterpoint to just about every social interaction. I argue that successful psychodynamic treatment allows immigrants to take the doubleness for granted, in effect seeing double and being double. In this way they come to effortlessly privilege one self-state over the other. The recognition and acceptance of competing self-states proves transformative in any treatment, but never more so than in working with immigrants who contend with several culturally competing selves in their daily lives and seek one relationship in which they can all be seen and heard. I describe treating an immigrant who, when I began to work with her, excelled at seeing double, but being double posed a terrifying dilemma. At least two self-states were engaged in a tug of war; she feared that the winner would take all. PMID- 26356776 TI - Giving birth in exile: motherhood as reterritorialization. AB - This paper explores the effects of exile on the subjectivity of pregnant migrant women through the lens of the processes of deterritorialization and reterritorialization. Having escaped the gaze of the parental superego, the subject's encounter with sexuality becomes possible. However, in addition to the emancipatory aspects of migration, we observe particular somatic-psychical effects on reproductive ability. These "exile" pregnancies are generally experienced as difficult and painful, laying bare a symptomatology that is as much psychical as somatic, and which highlights the cost of a desire for independence. In this context, where perinatal risks must be evaluated and treated through an interdisciplinary approach, a clinical accompaniment proves to be indispensable for the maternity to progress smoothly on foreign soil. PMID- 26356777 TI - Arieti and Bowlby: convergence and direct influence. AB - Arieti was a great specialist of schizophrenia and Bowlby was the initiator of attachment theory. Working independently on the two sides of the Atlantic, they converged on a range of topics, such as evolutionary theory, mourning, trauma, violence, and therapy as art and science. Later, Bowlby exerted a direct influence on Arieti, which Arieti acknowledged in his Love Can Be Found. Finally, the two authors cooperated in the second edition of the American Handbook of Psychiatry. PMID- 26356786 TI - Ultrafast Photoinduced Charge Separation in Wide-Band-Capturing Self-Assembled Supramolecular Bis(donor styryl)BODIPY-Fullerene Conjugates. AB - A new series of self-assembled supramolecular donor-acceptor conjugates capable of wide-band capture, and exhibiting photoinduced charge separation have been designed, synthesized and characterized using various techniques as artificial photosynthetic mimics. The donor host systems comprise of a 4,4-difluoro-4-bora 3a,4a-diaza-s-indacene (BODIPY) containing a crown ether entity at the meso position and two styryl entities on the pyrrole rings. The styryl end groups also carried additional donor (triphenylamine or phenothiazine) entities. The acceptor host system was a fulleropyrrolidine comprised of an ethylammonium cation. Owing to the presence of extended conjugation and multiple chromophore entities, the BODIPY host revealed absorbance and emission well into the near-IR region covering the 300-850 nm spectral range. The donor-acceptor conjugates formed by crown ether-alkyl ammonium cation binding of the host-guest system was characterized by optical absorbance and emission, computational, and electrochemical techniques. Experimentally determined binding constants were in the range of 1-2*10(5) M(-1) . An energy-level diagram to visualize different photochemical events was established using redox, computational, absorbance, and emission data. Spectral evidence for the occurrence of photoinduced charge separation in these conjugates was established from femtosecond transient absorption studies. The measured rates indicated ultrafast charge separation and relatively slow charge recombination revealing their usefulness in light-energy harvesting and optoelectronic device applications. The bis(donor styryl)BODIPY derived conjugates populated their triplet excited states during charge recombination. PMID- 26356787 TI - Theoretical study of the infrared frequencies of crystalline methyl acetate under interstellar medium conditions. AB - Identification of methyl acetate in the interstellar medium (ISM) and its spectroscopic studies have prompted us to investigate the structure of crystalline methyl acetate using numerical calculations. Here, we present a theoretical study of the structure of crystalline methyl acetate and its isotopologues and compare the calculated infrared (IR) spectra with the available experimental data. The optimized structure and vibrational properties were calculated using SIESTA software at 0 K. In the optimization process, the Perdew Burke-Ernzerhof functional and conjugate gradient methods were used with double zeta polarization basis functions. After optimization of the periodic structure, the vibrational frequencies and normal modes were calculated within the harmonic approximation. Using the calculated results, we refine the mode assignments of experimental work on crystalline methyl acetate and determine the low frequency modes (below 650 cm(-1)). To investigate the accuracy of the pseudopotential and confirm the IR frequencies, we performed molecular calculations using a periodic model of methyl acetate and its isotopologues using SIESTA and compared them with results obtained from Gaussian 09 (all electron method) calculations. Finally, we assigned the vibrational modes of crystalline CD3-COO-CH3 and CH3-COO-CD3, for which experimental data are not available in the crystalline phase under ISM conditions. For all of the calculation methods, the IR vibrational modes of molecular and crystalline methyl acetate and its isotopologues were in good agreement with the available experimental data and predict the unavailable values. PMID- 26356785 TI - Prophylaxis against Recurrence in Liver Transplantation Patients with Hepatitis B Virus: What is New? AB - Hepatitis B virus (HBV) causes an endemic infection that affects nearly 2 billion patients worldwide. It is one of the leading causes of liver cirrhosis, hepatocellular carcinoma (HCC), and liver transplantation (LT). Recurrence of HBV infection after LT is due to specific HBV-host genome interactions. Although hepatitis B immunoglobulin treatment constituted the backbone of HBV recurrence, use of the nucleoside and nucleotide analogs (especially the ones with a higher genetic barrier to resistance), either alone or in combination, offer us new and powerful options in overcoming this serious issue. PMID- 26356788 TI - Micelle enhanced and native spectrofluorimetric methods for determination of sertindole using sodium dodecyl sulfate as sensitizing agent. AB - Two stability indicating spectrofluorimetric methods were developed and validated for the determination of sertindole (SER) in the presence of its acid and oxidative degradates at lambda(ex) 257 nm and lambda(em) 335 nm. Method A was based on measuring the native fluorescence of SER using isopropanol as solvent. Method B was based on the enhancement of native fluorescence of SER quenched in aqueous media by using micellar microenvironment created by sodium dodecyl sulfate (SDS) anionic micelles using Britton Robinson Buffer (BRB) pH3.29 as solvent. Different factors affecting fluorescence intensity; both native and enhanced, were carefully studied to reach the optimum conditions of measurements. The proposed spectrofluorimetric methods were validated in accordance with ICH guidelines and were successfully applied for the determination of SER in bulk powder and pharmaceutical preparation with high sensitivity and stability indicating power. They were also statistically compared to the manufacturer methods with no significant difference in performance. PMID- 26356789 TI - Interstitial branch formation within the red nucleus by deep cerebellar nuclei derived commissural axons during target recognition. AB - Target recognition by developing axons is one of the fundamental steps for establishing the proper pattern of neuronal connectivity during development. However, knowledge of the mechanisms that underlie this critical event is still limited. In this study, to examine how commissural axons in vertebrates recognize their targets after crossing the midline, we analyzed in detail the behavior of postcrossing commissural axons derived from the deep cerebellar nuclei (DCN) in the developing mouse cerebellum. For this, we employed a cell-type-specific genetic labeling approach to selectively visualize DCN axons during the time when these axons project to the red nucleus (RN), one of the well-characterized targets of DCN axons. We found that, when DCN axons initially entered the RN at its caudal end, these axons continued to grow rostrally through the RN without showing noticeable morphological signs of axon branching. Interestingly, after a delay, DCN axons started forming interstitial branches from the portion of the axon shaft selectively within the RN. Because commissural axons acquire responsiveness to several guidance cues when they cross the midline, we further addressed whether midline crossing is a prerequisite for subsequent targeting by using a Robo3 knockdown strategy. We found that DCN axons were still capable of forming interstitial branches within the RN even in the absence of midline crossing. These results therefore suggest that the mechanism of RN recognition by DCN axons involves a delayed interstitial branching, and that these axons possess an intrinsic ability to respond to the target-derived cues irrespective of midline crossing. PMID- 26356790 TI - Relative Age Effect in Young Swiss Alpine Skiers From 2004 to 2011. AB - PURPOSE: To verify whether relative age effects (RAEs) occur among young male and female Swiss Alpine skiers of different age groups and performance levels. In addition, the efficacy of normalizing performance in physical tests to height and body mass to attenuate RAEs eventually present was tested. METHODS: The Swiss Ski Power Test consists of anthropometric measures and physical tests for coordination and speed, endurance, and strength and has been used since 2004 to evaluate 11- to 19-y-old Swiss competitive Alpine skiers. The authors analyzed the distribution of 6996 tests performed by 1438 male and 1031 female Alpine skiers between 2004 and 2011 according to the athletes' respective relative age quartiles. Differences in anthropometric measures and performance in physical tests according to quartile were assessed, and the possibility of attenuating eventual RAEs on performance by normalization of results to height and body mass was tested. RESULTS: RAEs were found among all female and male age groups, with no differences between age groups. While performance level did not affect RAE for male skiers, it influenced RAE among female skiers. RAEs also influenced results in all physical tests except upper-limb strength. Normalization of results to body mass attenuated most RAEs identified. CONCLUSION: Small RAEs are present among young Swiss competitive Alpine skiers and should be taken into account in training and selection settings to prevent the waste of possible future talents. When ranking junior athletes according to their performance in physical tests, normalization of results to body mass decreases the bias caused by RAEs. PMID- 26356791 TI - Cytologic appearance of a meningioma recurring over 4 years after initial diagnosis. PMID- 26356792 TI - Diagnosis and Management of Alcoholic Liver Disease. AB - Alcohol is a leading cause of liver disease and is associated with significant morbidity and mortality. Several factors, including the amount and duration of alcohol consumption, affect the development and progression of alcoholic liver disease (ALD). ALD represents a spectrum of liver pathology ranging from fatty change to fibrosis to cirrhosis. Early diagnosis of ALD is important to encourage alcohol abstinence, minimize the progression of liver fibrosis, and manage cirrhosis-related complications including hepatocellular carcinoma. A number of questionnaires and laboratory tests are available to screen for alcohol intake. Liver biopsy remains the gold-standard diagnostic tool for ALD, but noninvasive accurate alternatives, including a number of biochemical tests as well as liver stiffness measurement, are increasingly being utilized in the evaluation of patients with suspected ALD. The management of ALD depends largely on complete abstinence from alcohol. Supportive care should focus on treating alcohol withdrawal and providing enteral nutrition while managing the complications of liver failure. Alcoholic hepatitis (AH) is a devastating acute form of ALD that requires early recognition and specialized tertiary medical care. Assessment of AH severity using defined scoring systems is important to allocate resources and initiate appropriate therapy. Corticosteroids or pentoxifylline are commonly used in treating AH but provide a limited survival benefit. Liver transplantation represents the ultimate therapy for patients with alcoholic cirrhosis, with most transplant centers mandating a 6 month period of abstinence from alcohol before listing. Early liver transplantation is also emerging as a therapeutic measure in specifically selected patients with severe AH. A number of novel targeted therapies for ALD are currently being evaluated in clinical trials. PMID- 26356793 TI - Choline Derivate-Modified Doxorubicin Loaded Micelle for Glioma Therapy. AB - Ligand-mediated polymeric micelles have enormous potential for improving the efficacy of glioma therapy. Linear-dendritic drug-polymer conjugates composed of doxorubicin (DOX) and polyethylene glycol (PEG) were synthesized with or without modification of choline derivate (CD). The resulting MeO-PEG-DOX8 and CD-PEG-DOX8 could self-assemble into polymeric micelles with a nanosized diameter around 30 nm and a high drug loading content up to 40.6 and 32.3%, respectively. The optimized formulation 20% CD-PEG-DOX8 micelles had superior cellular uptake and antitumor activity against MeO-PEG-DOX8 micelles. The subcellular distribution using confocal study revealed that 20% CD-PEG-DOX8 micelles preferentially accumulated in the mitochondria. Pharmacokinetic study showed area under the plasma concentration-time curve (AUC0-t) and Cmax for 20% CD-PEG-DOX8 micelles and DOX solution were 1336.58 +/- 179.43 mg/L.h, 96.35 +/- 3.32 mg/L and 1.40 +/- 0.19 mg/L.h, 1.15 +/- 0.25 mg/L, respectively. Biodistribution study showed the DOX concentration of 20% CD-PEG-DOX8 micelles treated group at 48 h was 2.37-fold higher than that of MeO-PEG-DOX8 micelles treated group at 48 h and was 24 fold higher than that of DOX solution treated group at 24 h. CD-PEG-DOX8 micelles (20%) were well tolerated with reduced cardiotoxicity, as evaluated in the body weight change and HE staining studies, while they induced most significant antitumor activity with longest media survival time in an orthotopic mouse model of U87-luci glioblastoma model as displayed in the bioluminescence imaging and survival curve studies. Our findings consequently indicated that 20% CD-PEG-DOX8 micelles are promising drug delivery system for glioma chemotherapy. PMID- 26356795 TI - Atypical Unilateral Posterior Reversible Encephalopathy Syndrome Mimicking a Middle Cerebral Artery Infarction. AB - Posterior reversible encephalopathy syndrome (PRES) is usually a reversible clinical and radiological entity associated with typical features on brain MR or CT imaging. However, the not-so-uncommon atypical radiological presentations of the condition are also present and they may go unrecognised as they are confused with other conditions. Here, we report a very rare case of atypical, unilateral PRES in a 49-year-old uremic, post-transplant female patient who presented with seizures. Initial MRI showed high-grade occlusion of the left middle cerebral artery (MCA) and lesions suggestive of subacute infarction in the ipsilateral frontotemporoparietal lobe. Patient symptoms had resolved a day after the onset without any specific treatment but early follow-up CT findings suggested hemorrhagic transformation. Follow-up MRI performed 2 years later showed complete disappearence of the lesions and persisting MCA occlusion. PMID- 26356794 TI - Interaction Between the Neglected Tropical Disease Human Schistosomiasis and HCV Infection in Egypt: a Puzzling Relationship. AB - Egypt has the highest prevalence of chronic hepatitis C virus (HCV) infection and seropositivity worldwide, and it has been proposed that this enhanced susceptibility to HCV is related to coinfection with schistosomiasis. Although currently, there are no studies regarding the actual prevalence of both human schistosomiasis and schistosomiasis/HCV coinfection evidences strongly support that eliminating human schistosomiasis from Egypt is necessary to reduce both HCV prevalence and liver pathology. The present review highlights the significant impact of the neglected tropical disease human schistosomiasis on both susceptibility of Egyptians to HCV coinfection, severity of the resulting liver pathology, and poor response to antiviral therapy. The immune evasion mechanisms exerted by the HCV-NS3/4A protease domain, and the possible impact of immune evasion mechanisms exerted by proteases of larval, worm and egg stages of the parasite Schistosoma on human susceptibility to HCV infection are discussed. In addition, schistosome immune evasion mechanisms may include immunosuppression that in turn prevents clearance of HCV viremia and leads to relapsing HCV infection and severe liver pathology. I propose the generation of a replicon system from the most prevailing genotype (HCV-4a) in Egypt and establishing its replication on hepatoplastoma or immune cells in presence of bilharzial antigens. Finally, the use of a humanized small animal model that can acquire both HCV and S. mansoni infections will be important to further understand in real time the impact of coinfection on both the immune system and liver pathology. PMID- 26356796 TI - Detection of hypermutated human papillomavirus type 16 genome by Next-Generation Sequencing. AB - Human papillomavirus type 16 (HPV16) is a major cause of cervical cancer. We previously demonstrated that C-to-T and G-to-A hypermutations accumulated in the HPV16 genome by APOBEC3 expression in vitro. To investigate in vivo characteristics of hypermutation, differential DNA denaturation-PCR (3D-PCR) was performed using three clinical specimens obtained from HPV16-positive cervical dysplasia, and detected hypermutation from two out of three specimens. One sample accumulating hypermutations in both E2 and the long control region (LCR) was further subjected to Next-Generation Sequencing, revealing that hypermutations spread across the LCR and all early genes. Notably, hypermutation was more frequently observed in the LCR, which contains a viral replication origin and the early promoter. APOBEC3 expressed abundantly in an HPV16-positive cervix, suggesting that single-stranded DNA exposed during viral replication and transcription may be efficient targets for deamination. The results further strengthen a role of APOBEC3 in introducing HPV16 hypermutation in vivo. PMID- 26356798 TI - An Atomic-Scale View of CO and H2 Oxidation on a Pt/Fe3 O4 Model Catalyst. AB - Metal-support interactions are frequently invoked to explain the enhanced catalytic activity of metal nanoparticles dispersed over reducible metal oxide supports, yet the atomic-scale mechanisms are rarely known. In this report, scanning tunneling microscopy was used to study a Pt1-6/Fe3O4 model catalyst exposed to CO, H2, O2, and mixtures thereof at 550 K. CO extracts lattice oxygen atoms at the cluster perimeter to form CO2, creating large holes in the metal oxide surface. H2 and O2 dissociate on the metal clusters and spill over onto the support. The former creates surface hydroxy groups, which react with the support, ultimately leading to the desorption of water, while oxygen atoms react with Fe from the bulk to create new Fe3O4(001) islands. The presence of the Pt is crucial because it catalyzes reactions that already occur on the bare iron oxide surface, but only at higher temperatures. PMID- 26356797 TI - BK virus capsid antibodies are associated with protection against subsequent development of PML in HIV-infected patients. AB - Progressive multifocal leukoencephalopathy (PML) is caused by JC polyomavirus (JCPyV). Because a reciprocal relationship has been described between antibody levels to JCPyV and BK polyomavirus (BKPyV), we performed a nested case control study with pre-diagnostic serum samples from HIV infected subjects to examine the relationship between BKPyV capsid antibodies and the risk of PML. Serum samples collected 0.5-2 years before PML diagnosis from 25 cases (66 samples) and 80 matched controls (204 samples) were tested in ELISA for JCPyV, BKPyV type 1 and type 4 capsid antibodies. High levels of BKPyV 1 and 4 antibodies were associated with a lower risk of PML (BKPyV 1 OR, 0.56, 95% CI, 0.35-0.89; BKPyV 4 OR, 0.40, 95% CI, 0.24-0.0.67). Our study demonstrates that antibodies to BKPyV capsids are an immunological marker of protection against development of PML. Further studies are needed to define the mechanism. PMID- 26356799 TI - Update on Common Childhood Endocrine Disorders. PMID- 26356800 TI - Depletion, melting and reentrant solidification in mixtures of soft and hard colloids. AB - We present extensive experimental and theoretical investigations on the structure, phase behavior, dynamics and rheology of model soft-hard colloidal mixtures realized with large, multiarm star polymers as the soft component and smaller, compact stars as the hard one. The number and length of the arms in star polymers control their softness, whereas the size ratio, the overall density and the composition are additional parameters varied for the mixtures. A coarse grained theoretical strategy is employed to predict the structure of the systems as well as their ergodicity properties on the basis of mode coupling theory, for comparison with rheological measurements on the samples. We discovered that dynamically arrested star-polymer solutions recover their ergodicity upon addition of colloidal additives. At the same time the system displays demixing instability, and the binodal of the latter meets the glass line in a way that leads, upon addition of a sufficient amount of colloidal particles, to an arrested phase separation and reentrant solidification. We present evidence for a subsequent solid-to-solid transition well within the region of arrested phase separation, attributed to a hard-sphere-mixture type of glass, due to osmotic shrinkage of the stars at high colloidal particle concentrations. We systematically investigated the interplay of star functionality and size ratio with glass melting and demixing, and rationalized our findings by the depletion of the big stars due to the smaller colloids. This new depletion potential in which, contrary to the classic colloid-polymer case, the hard component depletes the soft one, has unique and novel characteristics and allows the calculation of phase diagrams for such mixtures. This work covers a broad range of soft-hard colloidal mixture compositions in which the soft component exceeds the hard one in size and provides general guidelines for controlling the properties of such complex mixtures. PMID- 26356802 TI - A prospective randomized study of the difference in diagnostic yield between endoscopic ultrasound-guided fine-needle aspiration (EUSFNA) needles with and without a side port in pancreatic masses. AB - BACKGROUND AND STUDY AIMS: Two 22G needles with similar designs, apart from the absence (A) or presence of a side port (B), are available for endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA). The side port was designed to increase diagnostic yield but this advantage was unproven. This study evaluated the difference in diagnostic yield between both needles in pancreatic masses. PATIENTS AND METHODS: This was a prospective multicenter randomized cross over study. Patients with pancreatic masses were randomized to one needle for the first two passes, followed by the other for the next two passes. A pathologist blinded to the needle assessed each puncture for cellularity and morphology. The diagnostic yield between both needles was compared. RESULTS: In total, 30 patients were recruited (mean lesion size: 3.5 cm, range: 1.2 - 6.3). Comparison of cellularity adequacy: first pass: A vs. B: 26/30 vs. 24/30 (P = 0.488): 2nd pass: A vs. B: 25/30 vs. 26/30 (P = 0.718). Comparison of diagnostic accuracy: first pass: A vs. B: 22/30 vs. 23/30 (P = 0.766); after two passes: A vs. B: 26/30 vs. 26/30 (P = 1.0). When all four passes were assessed, adequate cellularity was obtained in 29/30 and the correct diagnosis was obtained in 28/30 patients. There were no procedural complications. CONCLUSIONS: There was no significant difference in diagnostic yield between EUSFNA needles with or without a side port for pancreatic masses. STUDY REGISTRATION: NCT02092519. PMID- 26356801 TI - Association between colorectal polyps and hypertension treatment. AB - OBJECTIVE: Patients who take drugs regularly are increasing, not least due to metabolic and orthopedic diseases. In the present study we aimed to investigate the association between the use of drugs, such as non-steroidal anti-inflammatory drugs (NSAIDs) and low-dose aspirin, and colorectal polyps diagnosed based on colonoscopic findings. METHODS: In total, 1318 consecutive patients who underwent total colonoscopy for the first time were cross-sectionally analyzed. Personal data including comorbidities and all medications were obtained by a questionnaire. Their blood pressure, body weight and waist circumference were measured just before the colonoscopic examination. RESULTS: Colorectal polyps were found in 577 (43.8%) patients, with a prevalence of 57.6% (296/514) in patients receiving antihypertensive treatment and 35.0% (281/804) in patients not undergoing such treatment. A multivariate analysis showed that age, waist circumference, alcohol consumption, smoking and the use of antihypertensive drugs were independent risk factors for colorectal polyps. In a secondary multivariate analysis incorporating the parameters of measured blood pressure and medication status, the number of antihypertensive drugs was strongly associated with the risk of colorectal polyps, whereas blood pressure showed no significant association. CONCLUSIONS: The use of antihypertensive drug may be a risk factor for colorectal polyps. Furthermore, this risk increases with the intensive use of antihypertensive drugs. PMID- 26356803 TI - New Vaccines for the World's Poorest People. AB - The 2000 Millennium Development Goals helped stimulate the development of life saving childhood vaccines for pneumococcal and rotavirus infections while greatly expanding coverage of existing vaccines. However, there remains an urgent need to develop new vaccines for HIV/AIDS, malaria, and tuberculosis, as well as for respiratory syncytial virus and those chronic and debilitating (mostly parasitic) infections known as neglected tropical diseases (NTDs). The NTDs represent the most common diseases of people living in extreme poverty and are the subject of this review. The development of NTD vaccines, including those for hookworm infection, schistosomiasis, leishmaniasis, and Chagas disease, is being led by nonprofit product development partnerships (PDPs) working in consortia of academic and industrial partners, including vaccine manufacturers in developing countries. NTD vaccines face unique challenges with respect to their product development and manufacture, as well as their preclinical and clinical testing. We emphasize global efforts to accelerate the development of NTD vaccines and some of the hurdles to ensuring their availability to the world's poorest people. PMID- 26356804 TI - Biomechanical benefits of anterior offsetting of humeral head component in posteriorly unstable total shoulder arthroplasty: A cadaveric study. AB - Restoration of joint stability during total shoulder arthroplasty can be challenging in the face of severe glenoid retroversion. A novel technique of humeral head component anterior-offsetting has been proposed to address posterior instability. We evaluated the biomechanical benefits of this technique in cadaveric specimens. Total shoulder arthroplasty was performed in 14 cadaveric shoulders from 7 donors. Complementary shoulders were assigned to either 10 degrees or 20 degrees glenoid retroversion, with retroversion created by eccentric reaming. Two humeral head component offset positions were tested in each specimen: The anatomic (posterior) and anterior (reverse). With loads applied to the rotator cuff and deltoid, joint contact pressures and the force and energy required for posterior humeral head translation were measured. The force and energy required to displace the humeral head posteriorly increased significantly with the anterior offset position compared to the anatomic offset position. The joint contact pressures were significantly shifted anteriorly, and the joint contact area significantly increased with the anterior offset position. Anterior offsetting of the humeral head component increased the resistance to posterior humeral head translation, shifted joint contact pressures anteriorly, and increased joint contact area, thus, potentially increasing the joint stability in total shoulder arthroplasty with simulated glenoid retroversion. PMID- 26356806 TI - Does body satisfaction influence self-esteem in adolescents' daily lives? An experience sampling study. AB - This study examined, within the context of the Contingencies of Self-Worth model, state-based associations between self-esteem and body satisfaction using the experience sampling method. One hundred and forty-four adolescent girls (mean age = 14.28 years) completed up to 6 assessments per day for one week using Palm Digital Assistants, in addition to baseline measures of trait body satisfaction and self-esteem. Results showed considerable variation in both state-based constructs within days, and evidence of effects of body satisfaction on self esteem, but not vice versa. Although these state-based associations were small in size and weakened as the time lag between assessments increased for the sample as a whole, individual differences in the magnitude of these effects were observed and predicted by trait self-esteem and body satisfaction. Collectively, these findings offer support for key tenets of the Contingencies of Self-Worth model. PMID- 26356805 TI - TORC1 controls G1-S cell cycle transition in yeast via Mpk1 and the greatwall kinase pathway. AB - The target of rapamycin complex 1 (TORC1) pathway couples nutrient, energy and hormonal signals with eukaryotic cell growth and division. In yeast, TORC1 coordinates growth with G1-S cell cycle progression, also coined as START, by favouring the expression of G1 cyclins that activate cyclin-dependent protein kinases (CDKs) and by destabilizing the CDK inhibitor Sic1. Following TORC1 downregulation by rapamycin treatment or nutrient limitation, clearance of G1 cyclins and C-terminal phosphorylation of Sic1 by unknown protein kinases are both required for Sic1 to escape ubiquitin-dependent proteolysis prompted by its flagging via the SCF(Cdc4) (Skp1/Cul1/F-box protein) ubiquitin ligase complex. Here we show that the stabilizing phosphorylation event within the C-terminus of Sic1 requires stimulation of the mitogen-activated protein kinase, Mpk1, and inhibition of the Cdc55 protein phosphatase 2A (PP2A(Cdc55)) by greatwall kinase activated endosulfines. Thus, Mpk1 and the greatwall kinase pathway serve TORC1 to coordinate the phosphorylation status of Sic1 and consequently START with nutrient availability. PMID- 26356807 TI - Social cognition, psychopathological symptoms, and family functioning in a sample of inpatient adolescents using variable-centered and person-centered approaches. AB - The process of diagnosis and treatment planning for adolescents requires clinicians to integrate information about various domains of functioning especially: clinical signs and symptoms, social cognition and family functioning. In the current study we applied an integrative analytic approach to mirror case conceptualization by clinicians. Our analyses were performed on the data gathered from the 328 inpatient adolescents. We used a broad range of measures of social cognitive constructs, family functioning and parent-and self-reported psychopathology. Using a combination of variable-based (PCA) and person-centered (LCA) analyses we determined class membership of adolescents based on variation in social cognition, psychopathology, and family functioning. We identified five latent classes: two internalizing groups, two externalizing groups and a severe psychopathology group. Patterns of general hyperfunctioning (characterized by hypermentalizing and hypervigilance to emotional stimuli) and hypofunctioning (manifested in undermentalizing and under-reactivity to emotional stimuli), can be observed in these groups. PMID- 26356809 TI - Effects of foot position of the nonparetic side during sit-to-stand training on postural balance in patients with stroke. AB - [Purpose] We aimed to investigate postural balance after sit-to-stand (STS) training with different nonparetic foot positions in stroke patients. [Subjects] Thirty-six subjects who experienced a stroke (21 males, 15 females) participated and were divided into the symmetric foot position (SYMM), asymmetric foot position (ASYM), and step foot (STEP) groups. [Methods] Each group performed repetitive sit-to-stand training 5 times a week for 6 weeks. The timed up-and-go test (TUG), functional reach test (FRT), and F-mat system correcting the anterior/posterior (A-P) and medial/lateral (M-L) distance of the center of pressure (COP) were used to measure the static and dynamic postural balance pre- and postintervention. ANCOVA was used to analyze differences among groups, and preintervention variables were used as covariates. [Results] The TUG, FRT, and A P and M-L distance of the COP in the ASYM and STEP groups were significantly decreased after intervention compared with the SYMM group. All parameters in the STEP group were lower than those in the ASYM group, without a significant difference. [Conclusion] The asymmetric foot position during STS is a good intervention to improve the static and dynamic postural balance in stroke patients. Especially, using a step to change the foot position is effective in improving STS performance. PMID- 26356808 TI - PROSPER partnership delivery system: Effects on adolescent conduct problem behavior outcomes through 6.5 years past baseline. AB - We report long-term effects of the PROSPER delivery system for universal evidence based preventive interventions on adolescent conduct problem behaviors (CPBs). A cluster randomized trial included 28 school districts assigned to PROSPER or a control condition. Community-based teams in PROSPER condition school districts selected evidence-based interventions-a family-focused intervention in sixth grade and a school-based intervention the next year; follow-up assessments were conducted through 12th grade. CPBs were measured with 12 self-report items derived from the National Youth Survey. Intervention-control differences were tested via a multi-level Zero-Inflated Poisson (ZIP) model. Differences were significant from 9th through 12th grades; Relative Reduction Rates were between 10.1% and 14.5%. The intervention group was delayed in reaching a 10th grade reference level of CPBs by 10.7 months. Moderation analyses indicated stronger effects for early substance initiators. Findings suggest that the PROSPER delivery system has the potential to reduce CPBs in general populations. PMID- 26356810 TI - Pokemon siRNA Delivery Mediated by RGD-Modified HBV Core Protein Suppressed the Growth of Hepatocellular Carcinoma. AB - Hepatocellular carcinoma (HCC) is a deadly human malignant tumor that is among the most common cancers in the world, especially in Asia. Hepatitis B virus (HBV) infection has been well established as a high risk factor for hepatic malignance. Studies have shown that Pokemon is a master oncogene for HCC growth, suggesting it as an ideal therapeutic target. However, efficient delivery system is still lacking for Pokemon targeting treatment. In this study, we used core proteins of HBV, which is modified with RGD peptides, to construct a biomimetic vector for the delivery of Pokemon siRNAs (namely, RGD-HBc-Pokemon siRNA). Quantitative PCR and Western blot assays revealed that RGD-HBc-Pokemon siRNA possessed the highest efficiency of Pokemon suppression in HCC cells. In vitro experiments further indicated that RGD-HBc-Pokemon-siRNA exerted a higher tumor suppressor activity on HCC cell lines, evidenced by reduced proliferation and attenuated invasiveness, than Pokemon-siRNA or RGD-HBc alone. Finally, animal studies demonstrated that RGD-HBc-Pokemon siRNA suppressed the growth of HCC xenografts in mice by a greater extent than Pokemon-siRNA or RGD-HBc alone. Based on the above results, Pokemon siRNA delivery mediated by RGD-modified HBV core protein was shown to be an effective strategy of HCC gene therapy. PMID- 26356811 TI - Near-Infrared Transcranial Radiation for Major Depressive Disorder: Proof of Concept Study. AB - Transcranial near-infrared radiation (NIR) is an innovative treatment for major depressive disorder (MDD), but clinical evidence for its efficacy is limited. Our objective was to investigate the tolerability and efficacy of NIR in patients with MDD. We conducted a proof of concept, prospective, double-blind, randomized study of 6 sessions of NIR versus sham treatment for patients with MDD, using a crossover design. Four patients with MDD with mean age 47 +/- 14 (SD) years (1 woman and 3 men) were exposed to irradiance of 700 mW/cm(2) and a fluence of 84 J/cm(2) for a total NIR energy of 2.40 kJ delivered per session for 6 sessions. Baseline mean HAM-D17 scores decreased from 19.8 +/- 4.4 (SD) to 13 +/- 5.35 (SD) after treatment (t = 7.905; df = 3; P = 0.004). Patients tolerated the treatment well without any serious adverse events. These findings confirm and extend the preliminary data on NIR as a novel intervention for patients with MDD, but further clinical trials are needed to better understand the efficacy of this new treatment. This trial is registered with ClinicalTrials.gov NCT01538199. PMID- 26356812 TI - Dissolved Organic Nitrogen Inputs from Wastewater Treatment Plant Effluents Increase Responses of Planktonic Metabolic Rates to Warming. AB - Increased anthropogenic pressures on coastal marine ecosystems in the last century are threatening their biodiversity and functioning. Global warming and increases in nutrient loadings are two major stressors affecting these systems. Global warming is expected to increase both atmospheric and water temperatures and increase precipitation and terrestrial runoff, further increasing organic matter and nutrient inputs to coastal areas. Dissolved organic nitrogen (DON) concentrations frequently exceed those of dissolved inorganic nitrogen in aquatic systems. Many components of the DON pool have been shown to supply nitrogen nutrition to phytoplankton and bacteria. Predictions of how global warming and eutrophication will affect metabolic rates and dissolved oxygen dynamics in the future are needed to elucidate their impacts on biodiversity and ecosystem functioning. Here, we experimentally determine the effects of simultaneous DON additions and warming on planktonic community metabolism in the Baltic Sea, the largest coastal area suffering from eutrophication-driven hypoxia. Both bacterioplankton community composition and metabolic rates changed in relation to temperature. DON additions from wastewater treatment plant effluents significantly increased the activation energies for community respiration and gross primary production. Activation energies for community respiration were higher than those for gross primary production. Results support the prediction that warming of the Baltic Sea will enhance planktonic respiration rates faster than it will for planktonic primary production. Higher increases in respiration rates than in production may lead to the depletion of the oxygen pool, further aggravating hypoxia in the Baltic Sea. PMID- 26356813 TI - Triple-layer dissection of the lung adenocarcinoma transcriptome: regulation at the gene, transcript, and exon levels. AB - Lung adenocarcinoma is one of the most deadly human diseases. However, the molecular mechanisms underlying this disease, particularly RNA splicing, have remained underexplored. Here, we report a triple-level (gene-, transcript-, and exon-level) analysis of lung adenocarcinoma transcriptomes from 77 paired tumor and normal tissues, as well as an analysis pipeline to overcome genetic variability for accurate differentiation between tumor and normal tissues. We report three major results. First, more than 5,000 differentially expressed transcripts/exonic regions occur repeatedly in lung adenocarcinoma patients. These transcripts/exonic regions are enriched in nicotine metabolism and ribosomal functions in addition to the pathways enriched for differentially expressed genes (cell cycle, extracellular matrix receptor interaction, and axon guidance). Second, classification models based on rationally selected transcripts or exonic regions can reach accuracies of 0.93 to 1.00 in differentiating tumor from normal tissues. Of the 28 selected exonic regions, 26 regions correspond to alternative exons located in such regulators as tumor suppressor (GDF10), signal receptor (LYVE1), vascular-specific regulator (RASIP1), ubiquitination mediator (RNF5), and transcriptional repressor (TRIM27). Third, classification systems based on 13 to 14 differentially expressed genes yield accuracies near 100%. Genes selected by both detection methods include C16orf59, DAP3, ETV4, GABARAPL1, PPAR, RADIL, RSPO1, SERTM1, SRPK1, ST6GALNAC6, and TNXB. Our findings imply a multilayered lung adenocarcinoma regulome in which transcript-/exon-level regulation may be dissociated from gene-level regulation. Our described method may be used to identify potentially important genes/transcripts/exonic regions for the tumorigenesis of lung adenocarcinoma and to construct accurate tumor vs. normal classification systems for this disease. PMID- 26356814 TI - V-ATPase: a master effector of E2F1-mediated lysosomal trafficking, mTORC1 activation and autophagy. AB - In addition to being a master regulator of cell cycle progression, E2F1 regulates other associated biological processes, including growth and malignancy. Here, we uncover a regulatory network linking E2F1 to lysosomal trafficking and mTORC1 signaling that involves v-ATPase regulation. By immunofluorescence and time-lapse microscopy we found that E2F1 induces the movement of lysosomes to the cell periphery, and that this process is essential for E2F1-induced mTORC1 activation and repression of autophagy. Gain- and loss-of-function experiments reveal that E2F1 regulates v-ATPase activity and inhibition of v-ATPase activity repressed E2F1-induced lysosomal trafficking and mTORC1 activation. Immunoprecipitation experiments demonstrate that E2F1 induces the recruitment of v-ATPase to lysosomal RagB GTPase, suggesting that E2F1 regulates v-ATPase activity by enhancing the association of V0 and V1 v-ATPase complex. Analysis of v-ATPase subunit expression identified B subunit of V0 complex, ATP6V0B, as a transcriptional target of E2F1. Importantly, ATP6V0B ectopic-expression increased v-ATPase and mTORC1 activity, consistent with ATP6V0B being responsible for mediating the effects of E2F1 on both responses. Our findings on lysosomal trafficking, mTORC1 activation and autophagy suppression suggest that pharmacological intervention at the level of v-ATPase may be an efficacious avenue for the treatment of metastatic processes in tumors overexpressing E2F1. PMID- 26356815 TI - HOXA13 is a potential GBM diagnostic marker and promotes glioma invasion by activating the Wnt and TGF-beta pathways. AB - Homeobox (HOX) genes, including HOXA13, are involved in human cancer. We found that HOXA13 expression was associated with glioma grade and prognosis. Bioinformatics analysis revealed that most of the HOXA13-associated genes were enriched in cancer-related signaling pathways and mainly involved in the regulation of transcription. We transfected four glioma cell lines with Lenti-si HOXA13. HOXA13 increased cell proliferation and invasion and inhibited apoptosis. HOXA13 decreased beta-catenin, phospho-smad2, and phospho-smad3 in the nucleus and increased phospho-beta-catenin in the cytoplasm. Furthermore, downregulation of HOXA13 in orthotopic tumors decreased tumor growth. We suggest that HOXA13 promotes glioma progression in part via Wnt- and TGF-beta-induced EMT and is a potential diagnostic biomarker for glioblastoma and an independent prognostic factor in high-grade glioma. PMID- 26356816 TI - C-kit signaling promotes proliferation and invasion of colorectal mucinous adenocarcinoma in a murine model. AB - It was reported that the receptor tyrosine kinase (RTK) family often highly expressed in several mucinous carcinomas. In the present study, we established a murine model of colorectal mucinous adenocardinoma (CRMAC) by treating C57 mice [both wild type (WT) and loss-of-function c-kit mutant type (Wads-/-)] with AOM+DSS for 37 weeks and found that c-kit, a member of RTK family, clearly enhanced the tumor cell proliferation by decreasing p53 and increasing cyclin D1 through AKT pathway. Significantly, c-kit strongly promoted tumor cell invasiveness by increasing ETV4, which induced MMP7 expression and epithelial mesenchymal transition (EMT) via ERK pathway. In vitro up- or down-regulating c kit activation in human colorectal cancer HCT-116 cells further consolidated these results. In conclusion, our data suggested that the c-kit signaling obviously promoted proliferation and invasion of CRMAC. Therefore, targeting the c-kit signaling and its downstream molecules might provide the potential strategies for treatment of patients suffering from CRMAC in the future. PMID- 26356817 TI - An epigenetic auto-feedback loop regulates TGF-beta type II receptor expression and function in NSCLC. AB - The downregulation of transforming growth factor-beta (TGF-beta) type II receptor (TbetaRII) expression and function plays a pivotal role in the loss of the TGF beta-induced tumor suppressor function that contributes to lung cancer progression. The aberrant expression of miRNAs has been shown to be involved in the regulation of oncogenes and tumor suppressor genes. Our current study involving miRNA microarray, northern blot and QRT-PCR analysis shows an inverse correlation between miR-20a and TbetaRII expression in non-small cell lung cancer (NSCLC) tissues and cell lines. Stable expression of miR-20a downregulates TbetaRII in lung epithelial cells which results in an inhibition of TGF-beta signaling and attenuation of TGF-beta-induced cell growth suppression and apoptosis. Stable knock down of miR-20a increases TbetaRII expression and inhibits tumorigenicity of lung cancer cells in vivo. Oncogene c-Myc promotes miR 20a expression by activating its promoter leading to downregulation of TbetaRII expression and TGF-beta signaling. MiR-145, which is upregulated by TGF-beta, inhibits miR-20a expression by targeting c-Myc and upregulates TbetaRII expression. These correlations among miRNAs and cellular proteins are supported by TCGA public database using NSCLC specimens. These results suggest a novel mechanism for the loss of TbetaRII expression and TGF-beta-induced tumor suppressor functions in lung cancer through a complex auto-feedback loop TGF beta/miR-145/c-Myc/miR-20a/TbetaRII. PMID- 26356818 TI - RET mutation p.S891A in a Chinese family with familial medullary thyroid carcinoma and associated cutaneous amyloidosis binding OSMR variant p.G513D. AB - There are no reports on the relationship between familial medullary thyroid carcinoma (FMTC) associated with cutaneous amyloidosis (CA) and RET or OSMR/IL31RA gene mutations. In this study, we investigated a Chinese family with FMTC/CA and found a recurrent RET c.2671T>G (p.S891A) mutation in six of 17 family members. Three of the six p.S891A mutation carriers presented with medullary thyroid carcinoma (MTC). Of them, three (two with and one without MTC) were diagnosed as having combined lichen/macular biphasic CA. We also identified a novel RET variant, c.1573C>T (p.R525W) in five members. Of them, three carriers had no evidence of thyroid/skin or basal serum/stimulated calcitonin abnormalities. In vitro cell proliferation assay indicated that oncogenic activity of RET p.S891A was slightly enhanced by p.R525W, whereas p.R525W alone had no effect on cell proliferation. Meanwhile, we identified a novel OSMR variant, c.1538G>A (p.G513D) in seven members. We noticed that three OSMR p.G513D carriers presenting with CA also had the RET p.S891A mutation. Our investigation indicated that the RET p.S891A mutation combined with OSMR p.G513D may underlie a novel phenotype manifesting as FMTC and CA. PMID- 26356819 TI - Stathmin 1 inhibition amplifies ruxolitinib-induced apoptosis in JAK2V617F cells. AB - The JAK/STAT pathway is constitutively activated in myeloproliferative neoplasms and can be inhibited by ruxolitinib, a selective JAK1/2 inhibitor. The JAK2(V617F) mutation leads to constitutive STAT3 phosphorylation and potentially leads to inhibition of Stathmin 1 activity via STAT3. In support of this hypothesis, we found that, in HEL JAK2(V617F) cells, ruxolitinib treatment decreased STAT3 and Stathmin 1 association, induced Stathmin 1 activation and microtubule instability. Silencing of Stathmin 1 significantly reduced cell proliferation and clonal growth, and increased apoptosis induced by ruxolitinib. Stathmin 1 silencing also prevented ruxolitinib-induced microtubule instability. To phenocopy the effect of Stathmin 1 inhibition, cells were treated with paclitaxel, a microtubule-stabilizing drug, in association or not with ruxolitinib; combined treatment significantly increased apoptosis, when compared to monotherapy. Notably, Stathmin 1 mRNA levels were highly expressed in CD34(+) cells from primary myelofibrosis patients. We then proposed that an undesired effect of ruxolitinib treatment may constitute Stathmin 1 activation and microtubule instability in JAK2(V617F) cells. Induction of microtubule stability, through Stathmin 1 silencing or paclitaxel treatment, combined with ruxolitinib could be an effective strategy for promoting apoptosis in JAK2(V617F) cells. PMID- 26356820 TI - Bax-PGAM5L-Drp1 complex is required for intrinsic apoptosis execution. AB - Intrinsic apoptosis eliminates cells with damaged DNA and cells with dysregulated expression of oncogene. PGAM5, a member of the phosphoglycerate mutase family, has two splicing variants: PGAM5L (the long form) and PGAM5S (the short form). It has been well established that PGAM5 is at the convergent point of multiple necrosis pathways. However, the role of PGAM5 in intrinsic apoptosis is still controversial. Here we report that the PGAM5L, but not PGAM5S is a prerequisite for the activation of Bax and dephosphorylation of Drp1 in arenobufagin and staurosporine induced intrinsic apoptosis. Knockdown of PGAM5L inhibits the translocation of Bax to the mitochondria and reduces mitochondrial fission. The interaction between PGAM5L and Drp1 was observed in both arenobufagin and staurosporine treated HCT116 cells, but not in HCT116 Bax(-/-) cells. Bax transfection rescues the formation of the triplex in both arenobufagin and staurosporine stimulated HCT116 Bax(-/-) cells. Arenobufagin shows remarkable anti-cancer effects both in orthotropic and heterotropic CRC models and demonstrates less toxic effects as compared with that of cisplatin. Bax-PGAM5L Drp1 complex is detected in arenobufagin and staurosporine treated CRC cells in vitro and in arenobufagin and cisplatin treated tumor in vivo as well. In summary, our results demonstrate that Bax-PGAM5L-Drp1 complex is required for intrinsic apoptosis execution. PMID- 26356821 TI - Dehydroandrographolide, an iNOS inhibitor, extracted from Andrographis paniculata (Burm.f.) Nees, induces autophagy in human oral cancer cells. AB - Autophagy, which is constitutively executed at the basal level in all cells, promotes cellular homeostasis by regulating the turnover of organelles and proteins. Andrographolide and dehydroandrographolide (DA) are the two principle components of Andrographis paniculata (Burm.f.) Nees. and are the main contributors to its therapeutic properties. However, the pharmacological activities of dehydroandrographolide (DA) remain unclear. In this study, DA induces oral cancer cell death by activating autophagy. Treatment with autophagy inhibitors inhibited DA-induced human oral cancer cell death. In addition, DA increased LC3-II expression and reduced p53 expression in a time- and concentration-dependent manner. Furthermore, DA induced autophagy and decreased cell viability through modulation of p53 expression. DA-induced autophagy was triggered by an activation of JNK1/2 and an inhibition of Akt and p38. In conclusion, this study demonstrated that DA induced autophagy in human oral cancer cells by modulating p53 expression, activating JNK1/2, and inhibiting Akt and p38. Finally, an administration of DA effectively suppressed the tumor formation in the oral carcinoma xenograft model in vivo. This is the first study to reveal the novel function of DA in activating autophagy, suggesting that DA could serve as a new and potential chemopreventive agent for treating human oral cancer. PMID- 26356823 TI - The relative contributions of disease label and disease prognosis to Alzheimer's stigma: A vignette-based experiment. AB - BACKGROUND: The classification of Alzheimer's disease is undergoing a significant transformation. Researchers have created the category of "preclinical Alzheimer's," characterized by biomarker pathology rather than observable symptoms. Diagnosis and treatment at this stage could allow preventing Alzheimer's cognitive decline. While many commentators have worried that persons given a preclinical Alzheimer's label will be subject to stigma, little research exists to inform whether the stigma attached to the label of clinical Alzheimer's will extend to a preclinical disorder that has the label of "Alzheimer's" but lacks the symptoms or expected prognosis of the clinical form. RESEARCH QUESTIONS: The present study sought to correct this gap by examining the foundations of stigma directed at Alzheimer's. It asked: do people form stigmatizing reactions to the label "Alzheimer's disease" itself or to the condition's observable impairments? How does the condition's prognosis modify these reactions? METHODS: Data were collected through a web-based experiment with N = 789 adult members of the U.S. general population (median age = 49, interquartile range, 32-60, range = 18-90). Participants were randomized through a 3 * 3 design to read one of 9 vignettes depicting signs and symptoms of mild stage dementia that varied the disease label ("Alzheimer's" vs. "traumatic brain injury" vs. no label) and prognosis (improve vs. static vs. worsen symptoms). Four stigma outcomes were assessed: discrimination, negative cognitive attributions, negative emotions, and social distance. RESULTS: The study found that the Alzheimer's disease label was generally not associated with more stigmatizing reactions. In contrast, expecting the symptoms to get worse, regardless of which disease label those symptoms received, resulted in higher levels of perceived structural discrimination, higher pity, and greater social distance. CONCLUSION: These findings suggest that stigma surrounding pre-clinical Alzheimer's categories will depend highly on the expected prognosis attached to the label. They also highlight the need for models of Alzheimer's-directed stigma that incorporate attributions about the condition's mutability. PMID- 26356822 TI - Small molecule inhibition of the CHFR-PARP1 interaction as novel approach to overcome intrinsic taxane resistance in cancer. AB - The mitotic checkpoint protein CHFR has emerged as a major mediator of taxane resistance in cancer. Here we show that CHFR's PAR-binding zinc finger domain (PBZ) mediates a protein interaction with poly-ADP ribosylated PARP1 leading to stabilization of CHFR. Disruption of the CHFR-PARP1 interaction through either PARP1 shRNA-mediated knockdown or overexpression of a PBZ domain peptide induces loss of CHFR protein expression. In an attempt to exploit this observation therapeutically, and to develop compounds with synthetic lethality in combination with taxanes, we performed a high-throughput computational screen of 5,256,508 chemical structures against the published crystal structure of the CHFR PBZ domain to identify candidate small molecule CHFR protein-protein interaction inhibitors. The 10 compounds with the best docking scores (< -9.7) were used for further in vitro testing. One lead compound in particular, termed 'A3', completely disrupted the protein-protein interaction between CHFR and PARP1, resulting in the inhibition of mitotic checkpoint function, and led to therapeutic synergy with docetaxel in cell viability and colony formation assays. In mouse xenografts, i.p. administration of 'A3' led to a significant reduction in nuclear CHFR protein expression with a maximal effect 4 hours after administration, confirming relevant pharmacodynamics following the peak of 'A3' plasma concentration in vivo. Furthermore, combination of A3 and taxane led to significant reduction of implanted tumor size without increase in hematological, hepatic or renal toxicity. These findings provide a proof-of-principle that small molecule inhibition of CHFR PBZ domain interaction is a novel potential therapeutic approach to increase the efficacy of taxane-based chemotherapy in cancer. PMID- 26356824 TI - Evaluative language in physiotherapy practice: How does it contribute to the therapeutic relationship? AB - In physiotherapy, the therapeutic relationship--in which a therapist and patient work together to achieve treatment goals--is increasingly seen as the foundation of patient care. How the therapeutic relationship is established and enacted, however, is not well understood. One way to better understand the nature of the relationship is to examine how therapists and patients evaluate and inform each other about the patient's physical capacity, sensation, and emotions. As the patient and therapist's talk is the primary means to realise and exchange such evaluations, our focus is on evaluative language used by the therapist and patient in their interactions. The aim of this paper is to examine the language and function of evaluation in physiotherapy consultations. The study is a discourse analytic one using Appraisal Theory. In Appraisal Theory, language resources that speakers use to construe evaluations such as emotions, judgments of behaviour and aesthetics are expressed as a system. The sub-systems are Affect (expressing emotion), Judgment (assessing behaviour) and Appreciation (evaluating processes and objects). The data are a convenience sample of 18 consultations from two cultural and therapeutic settings: primary healthcare (Sweden, Australia); and hospital rehabilitation (Australia). The findings show that both patient and therapist utilise all sub-systems of Appraisal; however, use of the sub-systems by the therapist and patient differs functionally. Judgment and Appreciation play a central role in therapists' co-construction of patients' physical history and presenting problem. In contrast, patient Affect evaluations, mainly to do with emotions about loss of capacity and pain, are generally not followed up by the therapist. The findings suggest that while patients engage with the therapeutic relationship from a clinical and interpersonal perspective, therapists are more narrowly focused on their own clinical tasks. The study findings have implications for understandings of the therapeutic relationship in physiotherapy and can inform teaching. PMID- 26356825 TI - Democracy and self-rated health across 67 countries: A multilevel analysis. AB - Existing research has found a positive association between countries' level of democratic governance and the health of their populations, although that research is limited by the use of data from small numbers of high-income countries or aggregate data that do not assess individual-level health outcomes. We extend prior research by using multilevel World Health Survey (2002-2004) data on 313,554 individuals in 67 countries, and find that the positive association between democratic governance and self-rated health persists after adjusting for both individual- and country-level confounders. However, the mechanisms linking democracy and self-rated health remain unclear. Individual-level measures of socioeconomic status, and country-level measures of economic inequality and investments in public health and education, do not significantly mediate the association between democratic governance and self-rated health. The persistent association between democratic governance and health suggests that the political organization of societies may be an important upstream determinant of population health. PMID- 26356826 TI - Patient dissatisfaction in China: What matters. AB - Patient satisfaction is a focal concern of health-care delivery and an expected outcome of medical care. Recently, the violent conflict between doctors and patients in China has intensified. Patient dissatisfaction has been recognized as an important concern and an urgent issue in the reform of China's health care. The objectives of this study are to investigate the determinants of patient dissatisfaction attributed to patient, hospital, and health-care market characteristics, as well as to explore the major determinants in the context of China. Data from 2007 to 2010 Urban Resident Basic Medical Insurance Survey (URBMIS) are used in this study. A total of 13,336 patients are selected conditional on health-care utilization. Analysis of satisfaction is based on outpatient utilization (last 2 weeks' reference, 6393 individuals) and inpatient utilization (last 1-year reference, 6943 individuals). Satisfaction was measured as ordinal variables (scales 1-5). Ordinary least squares (OLS) regression and an ordered probit model are applied to investigate the determinants. Blinder-Oaxaca decomposition is further employed to detect the proportion each predictor's contribution. The results indicate that patients' gender, education, and insurance status are significantly related to patient satisfaction. Higher-level hospitals are found to negatively correlate with patient satisfaction. Lower competition in providers' market and a higher market share of private hospitals are found to positively correlate with patient dissatisfaction. Meanwhile, the survey indicates that "medical charges too expensive" is chiefly responsible for patient dissatisfaction. Our study provides empirical evidence on the determinants of patient dissatisfaction in China. In particular, the results indicate that establishing a high competition among various providers in the health-care market will act as a "double-edged sword," with great policy implications. PMID- 26356827 TI - Food insecurity, chronic illness, and gentrification in the San Francisco Bay Area: An example of structural violence in United States public policy. AB - Food insecurity continues to be a major challenge in the United States, affecting 49 million individuals. Quantitative studies show that food insecurity has serious negative health impacts among individuals suffering from chronic illnesses, including people living with HIV/AIDS (PLHIV). Formulating effective interventions and policies to combat these health effects requires an in-depth understanding of the lived experience and structural drivers of food insecurity. Few studies, however, have elucidated these phenomena among people living with chronic illnesses in resource-rich settings, including in the United States. Here we sought to explore the experiences and structural determinants of food insecurity among a group of low-income PLHIV in the San Francisco Bay Area. Thirty-four semi-structured in-depth interviews were conducted with low-income PLHIV receiving food assistance from a local non-profit in San Francisco and Alameda County, California, between April and June 2014. Interview transcripts were coded and analysed according to content analysis methods following an inductive-deductive approach. The lived experience of food insecurity among participants included periods of insufficient quantity of food and resultant hunger, as well as long-term struggles with quality of food that led to concerns about the poor health effects of a cheap diet. Participants also reported procuring food using personally and socially unacceptable strategies, including long-term dependence on friends, family, and charity; stealing food; exchanging sex for food; and selling controlled substances. Food insecurity often arose from the need to pay high rents exacerbated by gentrification while receiving limited disability income--a situation resulting in large part from the convergence of long-standing urban policies amenable to gentrification and an outdated disability policy that constrains financial viability. The experiences of food insecurity described by participants in this study can be understood as a form of structural violence, motivating the need for structural interventions at the policy level that extend beyond food-specific solutions. PMID- 26356828 TI - Detailed Morphological Changes of Foveoschisis in Patient with X-Linked Retinoschisis Detected by SD-OCT and Adaptive Optics Fundus Camera. AB - Purpose. To report the morphological and functional changes associated with a regression of foveoschisis in a patient with X-linked retinoschisis (XLRS). Methods. A 42-year-old man with XLRS underwent genetic analysis and detailed ophthalmic examinations. Functional assessments included best-corrected visual acuity (BCVA), full-field electroretinograms (ERGs), and multifocal ERGs (mfERGs). Morphological assessments included fundus photography, spectral-domain optical coherence tomography (SD-OCT), and adaptive optics (AO) fundus imaging. After the baseline clinical data were obtained, topical dorzolamide was applied to the patient. The patient was followed for 24 months. Results. A reported RS1 gene mutation was found (P203L) in the patient. At the baseline, his decimal BCVA was 0.15 in the right and 0.3 in the left eye. Fundus photographs showed bilateral spoke wheel-appearing maculopathy. SD-OCT confirmed the foveoschisis in the left eye. The AO images of the left eye showed spoke wheel retinal folds, and the folds were thinner than those in fundus photographs. During the follow-up period, the foveal thickness in the SD-OCT images and the number of retinal folds in the AO images were reduced. Conclusions. We have presented the detailed morphological changes of foveoschisis in a patient with XLRS detected by SD-OCT and AO fundus camera. However, the findings do not indicate whether the changes were influenced by topical dorzolamide or the natural history. PMID- 26356829 TI - Correction to Synthesis of Acyl Alkenylindium Reagents and Their Application in the Synthesis of (Z)-alpha,beta-Unsaturated Ketones via Palladium-Catalyzed Cross Coupling Reaction. PMID- 26356830 TI - The negative effects of chronic exposure to isoflurane on spermatogenesis via breaking the hypothalamus-pituitary-gonadal equilibrium. AB - This study aims to investigate the negative effects of chronic exposure to isoflurane on spermatogenesis and explore the underlying mechanisms. Sixty male rats were randomly allocated to two groups: control group, receiving no treatment, and anesthesia group, administrated exposure to isoflurane (2 ppm) for 25 consecutive days (1 h/day). The negative effects of chronic exposure to isoflurane were evaluated by analyzing the median eminence GnRH content, the relevant hormone levels, some sperm parameters and the mRNA expressions for some reproduction-related genes. Isoflurane significantly decreased the GnRH content and the serum gonadotrophin levels compared with the control group (p<0.01). Meanwhile, the mRNA expressions of GnRH in hypothalamus, GnRH receptor, luteinizing hormone (LH)-beta and follicle-stimulating hormone (FSH)-beta in pituitary, and LH receptor and FSH receptor in testes were also significantly inhibited (p<0.01). Furthermore, the mRNA expressions of androgen receptor (AR), kisspeptin encoded gene (Kiss-1) and its receptor (GPR54) in hypothalamus were significantly diminished by isoflurane (p<0.01). The results indicated that chronic exposure to isoflurane diminished the synthesis and secretion of GnRH by inhibiting the androgen-AR-Kisspeptin-GPR54 pathway and breaking the hypothalamic pituitary-gonadal equilibrium, and therefore it could inhibit spermatogenesis. PMID- 26356831 TI - The effects of forest conversion to oil palm on ground-foraging ant communities depend on beta diversity and sampling grain. AB - Beta diversity - the variation in species composition among spatially discrete communities - and sampling grain - the size of samples being compared - may alter our perspectives of diversity within and between landscapes before and after agricultural conversion. Such assumptions are usually based on point comparisons, which do not accurately capture actual differences in total diversity. Beta diversity is often not rigorously examined. We investigated the beta diversity of ground-foraging ant communities in fragmented oil palm and forest landscapes in Sabah, Malaysia, using diversity metrics transformed from Hill number equivalents to remove dependences on alpha diversity. We compared the beta diversities of oil palm and forest, across three hierarchically nested sampling grains. We found that oil palm and forest communities had a greater percentage of total shared species when larger samples were compared. Across all grains and disregarding relative abundances, there was higher beta diversity of all species among forest communities. However, there were higher beta diversities of common and very abundant (dominant) species in oil palm as compared to forests. Differences in beta diversities between oil palm and forest were greatest at the largest sampling grain. Larger sampling grains in oil palm may generate bigger species pools, increasing the probability of shared species with forest samples. Greater beta diversity of all species in forest may be attributed to rare species. Oil palm communities may be more heterogeneous in common and dominant species because of variable community assembly events. Rare and also common species are better captured at larger grains, boosting differences in beta diversity between larger samples of forest and oil palm communities. Although agricultural landscapes support a lower total diversity than natural forests, diversity especially of abundant species is still important for maintaining ecosystem stability. Diversity in agricultural landscapes may be greater than expected when beta diversity is accounted for at large spatial scales. PMID- 26356832 TI - Hand Hygiene Compliance in an Emergency Department: The Effect of Crowding. AB - OBJECTIVES: Emergency department (ED) crowding results from the need to see high volumes of patients of variable acuity within a limited physical space. ED crowding has been associated with poor patient outcomes and increased mortality. The authors evaluated whether ED crowding is also associated with reduced hand hygiene compliance among health care workers. METHODS: A trained observer measured hand hygiene compliance using standardized definitions for 22 months in the 40-bed ED of a 475-bed academic hospital in Toronto, Ontario, Canada. ED crowding measures, including mean daily patient volumes, time to initial physician assessment, and daily nursing hours, were obtained from hospital administrative and human resource databases. Known predictors of hand hygiene compliance, including the indication for hand hygiene and the health care workers' professions, were also measured. Hand hygiene data, measured during 20 minute observation sessions, were linked to aggregate daily results for each crowding metric. Crowding metrics and known predictors of hand hygiene compliance were then included in a multivariate model if associated with hand hygiene compliance at a p-value of <0.20. RESULTS: Hand hygiene compliance was 29% (325 of 1,116 opportunities). Alcohol-based hand rinse was used 66% of the time. Nurses accounted for 68% of hand hygiene opportunities and physicians for 18%, with the remaining 14% attributed to nonphysician, nonnurse health care workers. The most common indications for hand hygiene were hand hygiene prior to (35%) and hand hygiene following (52%) contact with the patient or his or her environment. In multivariate analysis, time to physician assessment > 1.5 hours was associated with lower compliance (odds ratio [OR] = 0.67, 95% confidence interval [CI] = 0.51 to 0.89). Additionally, compliance was lower for nonnurse, nonphysician health care workers (OR = 0.51, 95% CI = 0.33 to 0.79) and higher for hand hygiene performed after contact with the patients or his/her environment, compared to hand hygiene performed before contact with the patient or his/her environment (OR = 2.0, 95% CI = 1.5 to 2.7). Daily patient volumes and nursing hours were not associated with hand hygiene compliance. CONCLUSIONS: ED hand hygiene compliance was low. Increased time to physician assessment was associated with reduced compliance, suggesting an association between crowding and compliance. Strategies that minimize ED crowding may improve ED hand hygiene compliance. PMID- 26356833 TI - Thermochemistry of the Reaction of SF6 with Gas-Phase Hydrated Electrons: A Benchmark for Nanocalorimetry. AB - The reaction of sulfur hexafluoride with gas-phase hydrated electrons (H2O)n(-), n ~ 60-130, is investigated at temperatures T = 140-300 K by Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry. SF6 reacts with a temperature independent rate of 3.0 +/- 1.0 * 10(-10) cm(3) s(-1) via exclusive formation of the hydrated F(-) anion and the SF5(*) radical, which evaporates from the cluster. Nanocalorimetry yields a reaction enthalpy of DeltaHR,298K = 234 +/- 24 kJ mol(-1). Combined with literature thermochemical data from bulk aqueous solution, these result in an F5S-F bond dissociation enthalpy of DeltaH298K = 455 +/- 24 kJ mol(-1), in excellent agreement with all high-level quantum chemical calculations in the literature. A combination with gas-phase literature thermochemistry also yields an experimental value for the electron affinity of SF5(*), EA(SF5(*)) = 4.27 +/- 0.25 eV. PMID- 26356834 TI - Temporal trends in clinical characteristics, management and prognosis of patients with symptomatic heart failure in Japan -- report from the CHART Studies. AB - BACKGROUND: Temporal trends in clinical characteristics, management and prognosis of patients with symptomatic heart failure (HF) remain to be elucidated in Japan. METHODS AND RESULTS: From the Chronic Heart Failure Analysis and Registry in the Tohoku District-1 (CHART-1; 2000-2005, n=1,278) and CHART-2 (2006-present, n=10,219) Studies, we enrolled 1,006 and 3,676 consecutive symptomatic stage C/D HF patients, respectively. As compared with the patients in the CHART-1 Study, those in the CHART-2 Study had similar age and sex prevalence, and were characterized by lower brain natriuretic peptide, higher prevalence of preserved left ventricular ejection fraction (LVEF) and higher prevalence of hypertension, diabetes mellitus and ischemic heart disease (IHD), particularly IHD with LVEF >=50%. From CHART-1 to CHART-2, use of renin-angiotensin system inhibitors, beta blockers and aldosterone antagonists was significantly increased, while that of loop diuretics and digitalis was decreased. Three-year incidences of all-cause death (24 vs. 15%; adjusted hazard ratio [adjHR], 0.73; P<0.001), cardiovascular death (17 vs. 7%; adjHR, 0.38; P<0.001) and hospitalization for HF (30 vs. 17%; adjHR, 0.51; P<0.001) were all significantly decreased from CHART-1 to CHART-2. In the CHART-2 Study, use of beta-blockers was associated with improved prognosis in patients with LVEF <50%, while that of statins was associated with improved prognosis in those with LVEF >=50%. CONCLUSIONS: Along with implementation of evidence-based medications, the prognosis of HF patients has been improved in Japan. ( TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT00418041) PMID- 26356835 TI - Incremental benefit of coronary artery calcium score above traditional risk factors for all-cause mortality in asymptomatic Korean adults. AB - BACKGROUND: Coronary artery calcium score (CACS) is a well-recognized marker for subclinical coronary atherosclerosis, particularly in asymptomatic populations. To date, however, the added prognostic benefit of CACS compared with traditional risk factors in an Asian population remains unknown. This study therefore investigated the benefit of CACS over traditional risk factors for all-cause mortality in a large multicenter registry of asymptomatic Korean adults. METHODS AND RESULTS: A total of 34,386 individuals were retrospectively enrolled to participate in a general health examination. The Framingham 10-year risk score (FRS) was calculated according to the traditional risk stratification algorithm and CACS was calculated in log(CACS+1) for continuous data and categorized as 0, 1-100, 101-400 and >400. During a median follow-up of 4.9 years (IQR, 3.0-7.1), there were 303 all-cause deaths (0.9%). Following adjustment, CACS was independently associated with all-cause death (hazard ratio, 1.10; 95% confidence interval (CI): 1.05-1.17; P<0.001). Notably, CACS added further prognostic value above and beyond FRS (likelihood ratio, chi(2)=75.42, P<0.001; continuous net reclassification improvement=0.40, 95% CI: 0.29-0.51, P<=0.001; improving C statistic from 0.64, 95% CI: 0.61-0.67 to 0.68, 95% CI: 0.64-0.71; ?C=0.04, 95% CI: 0.01-0.06, P=0.002). CONCLUSIONS: In an asymptomatic Korean population, CACS improved prediction of all-cause mortality over and above that of a conventional risk tool. PMID- 26356836 TI - Increased variability of the coupling interval of premature ventricular contractions as a predictor of cardiac mortality in patients with left ventricular dysfunction. AB - BACKGROUND: The characteristics and prognostic value of the variability of premature ventricular contraction (PVC) coupling intervals (CIs) for cardiac mortality are not yet decisive. METHODS AND RESULTS: In 133 consecutive patients (58+/-14 years old, 53 women) who had left ventricular dysfunction (LVD: ejection fraction <50%) and frequent PVCs (>=10/h) who underwent 24-h ambulatory electrocardiography (AECG) recording and (123)I-metaiodobenzylguanidine myocardial single-photon emission computed tomography simultaneously, the heart rate turbulence onset, slope, and T-wave alternans were analyzed from the 24-h AECG. The CI of the PVCs (MEANNV), standard deviation of the CI of the PVCs (SDNV) as an index of the variability of the PVC CI, and their ratio to the preceding N-N intervals (SDNV/SDNN) were calculated from constructed Poincare plots using the annotated 24-h AECG QRS data. The primary endpoint was cardiac mortality. The mean follow-up period was 63 months. Among 133 patients, 114 survived (group 1) and 19 (14%, group 2) died during the follow-up. The MEANNVand SDNVwere higher in group 2 (539+/-104 vs. 599+/-114 ms, P=0.021; 64+/-34 vs. 83+/ 37 ms, P=0.022, respectively). The SDNV, PVC count, and delayed heart/mediastinum ratio remained as significant predictors of cardiac mortality in the binary logistic regression analysis. CONCLUSIONS: These results suggest that the SDNVcould be another adjunctive parameter for predicting cardiac mortality in LVD. PMID- 26356837 TI - G Protein-Coupled Estrogen Receptor 1 Mediates Acute Estrogen-Induced Cardioprotection via MEK/ERK/GSK-3beta Pathway after Ischemia/Reperfusion. AB - Three types of estrogen receptors (ER) exist in the heart, Esr1, Esr2 and the G protein-coupled estrogen receptor 1, Gper1. However, their relative importance in mediating estrogen protective action is unknown. We found that, in the male mouse ventricle, Gper1 transcripts are three- and seventeen-fold more abundant than Esr1 and Esr2 mRNAs, respectively. Analysis of the three ER knockouts (Esr1-/-, Esr2-/- and Gper1-/-) showed that only the Gper1-/- hearts lost their ability to be protected by 40 nM estrogen as measured by heart function, infarct size and mitochondrial Ca2+ overload, an index of mitochondrial permeability transition pore (mPTP) activity. Analysis of Akt, ERK1/2 and GSK-3beta salvage kinases uncovered Akt and ERK1/2 transient activation by estrogen whose phosphorylation increased during the first 5 min of non-ischemic perfusion. All these increase in phosphorylation effects were abrogated in Gper1-/-. Inhibition of MEK1/2/ERK1/2 (1 MUM U0126) and PI-3K/Akt (10 MUM LY294002) signaling showed that the MEK1/2/ERK1/2 pathway via GSK-3beta exclusively was responsible for cardioprotection as an addition of U0126 prevented estrogen-induced GSK-3beta increased phosphorylation, resistance to mitochondrial Ca2+-overload, functional recovery and protection against infarction. Further, inhibiting PKC translocation (1 MUM chelerythrin-chloride) abolished estrogen-induced cardioprotection. These data indicate that estrogen-Gper1 acute coupling plays a key role in cardioprotection against ischemia/reperfusion injury in male mouse via a cascade involving PKC translocation, ERK1/2/GSK-3beta phosphorylation leading to the inhibition of the mPTP opening. PMID- 26356838 TI - CDC Grand Rounds: Addressing Preparedness Challenges for Children in Public Health Emergencies. AB - Recent public health emergencies including Hurricane Katrina (2005), the influenza H1N1 pandemic (2009), and the Ebola virus disease outbreak in West Africa (2014-2015) have demonstrated the importance of multiple-level emergency planning and response. An effective response requires integrating coordinated contributions from community-based health care providers, regional health care coalitions, state and local health departments, and federal agency initiatives. This is especially important when planning for the needs of children, who make up 23% of the U.S. population (1) and have unique needs that require unique planning strategies. PMID- 26356839 TI - Glaucoma Surgery and Anticoagulant Therapy--Reply. PMID- 26356840 TI - Lime Juice and Vinegar Injections as a Cheap and Natural Alternative to Control COTS Outbreaks. AB - Outbreaks of the corallivorous crown-of-thorns seastar Acanthaster planci (COTS) represent one of the greatest disturbances to coral reef ecosystems in the Indo Pacific, affecting not only coral reefs but also the coastal communities which rely on their resources. While injection approaches are increasingly used in an attempt to control COTS densities, most of them display severe drawbacks including logistical challenges, high residual environmental impacts or low cost effectiveness. We tested a new alternative control method based upon acidic injections of cheap, 100% natural products. We investigated the lethal doses, intra- and inter-specific disease transmission and immune responses of COTS when injected with fresh lime juice (extracted from local Citrus arantifolia) and white spirit vinegar. High COTS mortality was achieved with small volumes: 10-20 ml per seastar induced death in 89%/97% of injected specimens after an average 34.3 h/29.8 h for lime juice and vinegar respectively. Highest efficiency was reached for both solutions with double shots of (2 * 10 ml) in two different areas on the body: 100% mortality occurred within 12-24 h, which is similar or faster compared with other current injection methods. Multiple immune measures suggested that death was very likely caused by pH stress from the acidic solutions rather than a bacterial infection. Contagion to either conspecifics or a variety of other reef species was not observed, even at COTS densities 15 times higher than the highest naturally reported. 10 to 20 l lime juice/vinegar could kill up to a thousand COTS at a cost of less than 0.05 USD per specimen; no permits or special handling procedures are required. We conclude that injections of lime juice and vinegar offer great advantages when compared to current best practises and constitute a cheap and natural option for all reefs affected by COTS. PMID- 26356841 TI - Alcohol Use and Gamma-Glutamyltransferase Using a Mendelian Randomization Design in the Guangzhou Biobank Cohort Study. AB - BACKGROUND: Observational studies and small intervention studies suggest alcohol raises gamma-glutamyltransferase (GGT). We used Mendelian randomization to assess the causal effect of alcohol use on GGT in older Chinese people. METHODS: An instrumental variable (IV) analysis in 2,321 men and 2,757 women aged 50+ years from phase 3 of the Guangzhou Biobank Cohort Study with ALDH2 (rs671) genotyped, alcohol use and GGT available was used to assess the causal effect of alcohol use on GGT. Rs671 was used as an IV and F-statistics was used to test for weak instrument hypothesis. An F-statistic of >=10 indicates the IV is not weak. RESULTS: In men, the F-statistic for rs671 on alcohol use was 70. Using IV analysis alcohol use increased GGT by 10.60 U/L per alcohol unit (10 gram ethanol) per day (95% confidence interval (CI) 6.58 to 14.62). The estimate was lower in observational multivariate regression: 3.48 U/L GGT per alcohol unit per day (95% CI 2.84 to 4.11) adjusted for age, education, physical activity and smoking. In women, rs671 was not associated with alcohol or GGT and the F statistic was 7 precluding IV analysis. CONCLUSION: In Mendelian randomization, we found confirmative evidence that alcohol use increases GGT among Southern Chinese men. Moreover, we found that the ALDH2 variant rs671 was not associated with GGT among Southern Chinese women who generally consume very low levels of alcohol. Taken together our findings strongly suggest that alcohol increases GGT, although we cannot rule out the possibility that other unknown factors may cause a different relation between alcohol and GGT in other populations. PMID- 26356843 TI - Unexpected Cardiac Masses. PMID- 26356842 TI - Meta-Analysis of the Detection of Plant Pigment Concentrations Using Hyperspectral Remotely Sensed Data. AB - Passive optical hyperspectral remote sensing of plant pigments offers potential for understanding plant ecophysiological processes across a range of spatial scales. Following a number of decades of research in this field, this paper undertakes a systematic meta-analysis of 85 articles to determine whether passive optical hyperspectral remote sensing techniques are sufficiently well developed to quantify individual plant pigments, which operational solutions are available for wider plant science and the areas which now require greater focus. The findings indicate that predictive relationships are strong for all pigments at the leaf scale but these decrease and become more variable across pigment types at the canopy and landscape scales. At leaf scale it is clear that specific sets of optimal wavelengths can be recommended for operational methodologies: total chlorophyll and chlorophyll a quantification is based on reflectance in the green (550-560nm) and red edge (680-750nm) regions; chlorophyll b on the red, (630 660nm), red edge (670-710nm) and the near-infrared (800-810nm); carotenoids on the 500-580nm region; and anthocyanins on the green (550-560nm), red edge (700 710nm) and near-infrared (780-790nm). For total chlorophyll the optimal wavelengths are valid across canopy and landscape scales and there is some evidence that the same applies for chlorophyll a. PMID- 26356844 TI - Smaller Cigarette Pack as a Commitment to Smoke Less? Insights from Behavioral Economics. AB - Cigarettes are commonly sold in packs of 20 units and therefore little is known about the potential impact of pack size on consumption. Using insights from behavioral economics, we suggest that cigarette packs smaller than the standard size may help some smokers cut back and/or quit, consistent with their long-term goals. Results from an online hypothetical purchase experiment conducted in a sample of US smokers reveal that over a third of smokers are willing to pay a price premium to purchase in smaller quantities. Further, a desire to quit smoking and high self-control is associated with preference for a smaller pack. While we provide some preliminary evidence that smaller packs may be beneficial to certain types of smokers, further research should be conducted to assess whether the smaller pack size should be considered in the arsenal of tobacco control policies to help current smokers quit (JEL: I18; I12; D12). PMID- 26356845 TI - Differential Effects of Conservational Management on SOC Accumulation in the Grasslands of China. AB - Conservational management practices in grasslands have been considered one of the efficient options to enhance the soil organic carbon (SOC) accumulation. However, the SOC changes after the conservational management practices vary significantly under different grassland vegetation types and the environmental conditions. At present, it is not clear how the SOC accumulation changes along the soil profile if conservational management practice was adopted. In this study, we collected 663 paired observational data of SOC changes with and without conservational management practices in grasslands of China from 176 published literatures that has both the surface (0-20 cm) and subsurface (to 40 cm depth) SOC measurements. The differences of SOC density (SOCD) between pre-management and post-management in the vertical soil layers were analyzed in order to establish a quantitative relationship of the SOC changes between the subsurface and the surface. The results revealed that in all grasslands, conservational management practices benefits the SOC accumulation by enhancing 0.43-1.14 Mg C ha-1 yr-1. But the SOC increment weakened downwards along the soil profile. While the surface SOC was enhanced by 17% after conservational management, the subsurface SOC was enhanced by only 7%. The SOC accumulation was closely correlated with restoration duration, pre-management SOCD and the environmental factors and differed greatly among different grasslands and the practices adopted. The alpine and mountain grassland showed a higher annual SOC increment than the temperate grassland with the annual rate of 1.62 and 0.72 Mg C ha-1 yr-1, respectively. The SOC increment caused by the artificial plantation and the grazing exclusion conservational management was more than 2-fold that of the cropland abandonment and the extensive utilization. With the quantitative relationship of the SOC changes between soil layers, we provide a methodological option to estimate SOC changes to layers deeper than the recommendation of IPCC when only the surface layer SOC increment is available. PMID- 26356846 TI - One-cm Versus 2-cm Excision Margins for Patients With Intermediate Thickness Melanoma: A Matched-Pair Analysis. AB - BACKGROUND: Optimum excision margins used in the removal of intermediate thickness melanomas remain unclear. OBJECTIVE: This study's aim was to compare the clinical outcomes of 1-cm margins with 2-cm margins in patients with a tumor thickness of 1.1- to 4.0-mm. MATERIALS AND METHODS: This was a retrospective study, which was based on a matched-pairs design. Equal patient cohorts were constructed in terms of gender, age, Breslow thickness, and the anatomic location of the primary lesion. There were 80 patients whom underwent an excision with a 1 cm margin and 80 patients with a 2-cm margin. Follow-up data were analyzed by the Kaplan-Meier method and a Cox regression model. RESULTS: After a median follow-up time of 41 months, there were no differences in relapse-free survival or melanoma specific survival between study groups. The wound was closed directly in 62 patients (78%) in the 1-cm group and in 36 patients (45%) in the 2-cm group (p < .001). CONCLUSION: A 1-cm excision margin may be sufficient in melanomas of 1.1 to 2.0 mm in Breslow thickness based on these findings of low recurrence. With thicker tumors (2.1-4.0 mm), this recommendation cannot be given due to inherent study limitations. PMID- 26356847 TI - Avoiding and Treating Blindness From Fillers: A Review of the World Literature. AB - BACKGROUND: As the popularity of soft tissue fillers increases, so do the reports of adverse events. The most serious complications are vascular in nature and include blindness. OBJECTIVE: To review the cases of blindness after filler injection, to highlight key aspects of the vascular anatomy, and to discuss prevention and management strategies. METHODS: A literature review was performed to identify all the cases of vision changes from filler in the world literature. RESULTS: Ninety-eight cases of vision changes from filler were identified. The sites that were high risk for complications were the glabella (38.8%), nasal region (25.5%), nasolabial fold (13.3%), and forehead (12.2%). Autologous fat (47.9%) was the most common filler type to cause this complication, followed by hyaluronic acid (23.5%). The most common symptoms were immediate vision loss and pain. Most cases of vision loss did not recover. Central nervous system complications were seen in 23.5% of the cases. No treatments were found to be consistently successful in treating blindness. CONCLUSION: Although the risk of blindness from fillers is rare, it is critical for injecting physicians to have a firm knowledge of the vascular anatomy and to understand key prevention and management strategies. PMID- 26356848 TI - Treatment Algorithm and Clinical Outcome of Venous Malformations of the Limbs. AB - BACKGROUND: Venous malformations of the limbs are congenital low-flow vascular anomalies. A treatment is reasonable if they are symptomatic or if a progressive lesion may affect functional structures. OBJECTIVE: The purpose of this work is the presentation of clinical results after treatment of venous malformations of the limbs according to the standard algorithm used at the University Hospital of Tuebingen, Germany. PATIENTS AND METHODS: Between January 2008 and June 2015, patients with venous malformations of the limbs were subjected to either percutaneous sclerotherapy or surgical excision according to this treatment algorithm. Remaining symptoms such as pain level and disturbing appearance before and after treatment as well as overall satisfaction was assessed the earliest 3 months after last treatment. RESULTS: Thirty-nine patients with venous malformations of the limbs were subjected to either 1 or more percutaneous sclerotherapies (n = 19) or surgical excision (n = 21). There were no serious complications that needed surgical revision. There was a statistically significant reduction in the pain level and disturbing appearance after both sclerotherapy and surgical excision (p < .05) in 30 cases in total. The overall treatment satisfaction was rated 7.9/10 and 8.8/10 after sclerotherapy and surgical excision, respectively. CONCLUSION: A low complication rate with a high patient satisfaction could be achieved after this treatment algorithm for venous malformations of the limbs. PMID- 26356849 TI - Upstaging From Melanoma in Situ to Invasive Melanoma on the Head and Neck After Complete Surgical Resection. AB - BACKGROUND: Melanoma in situ (MIS) diagnosed from a subtotal biopsy may be upstaged to invasive melanoma after resection. The frequency of this phenomenon is markedly variable. OBJECTIVE: To quantify the rate of upstaging MIS on the head and neck after resection at this institution, characterize the location of the invasive component relative to the clinically evident lesion, and determine the rate of upstaging with time. MATERIALS AND METHODS: The authors retrospectively reviewed clinical records of adult patients with a preoperative diagnosis of MIS on the head and neck from January 1994 to August 2012. Patient and tumor characteristics were recorded. RESULTS: In total, 624 patients met the inclusion criteria and 24 (4%) were upstaged after resection. Four patients had invasive disease beyond the clinically evident lesion. The annual percentage of upstaged lesions seemed to show an increasing trend with time. CONCLUSION: Upstaging of MIS on the head and neck occurs at a relatively low rate that may be increasing with time. Invasive components of lentigo maligna melanoma may exist beyond the clinically evident margins. Histological examination of the maximal amount of the surgical specimen is paramount for optimal staging and treatment of MIS. PMID- 26356850 TI - Kidney segmentation in CT sequences using SKFCM and improved GrowCut algorithm. AB - BACKGROUND: Organ segmentation is an important step in computer-aided diagnosis and pathology detection. Accurate kidney segmentation in abdominal computed tomography (CT) sequences is an essential and crucial task for surgical planning and navigation in kidney tumor ablation. However, kidney segmentation in CT is a substantially challenging work because the intensity values of kidney parenchyma are similar to those of adjacent structures. RESULTS: In this paper, a coarse-to fine method was applied to segment kidney from CT images, which consists two stages including rough segmentation and refined segmentation. The rough segmentation is based on a kernel fuzzy C-means algorithm with spatial information (SKFCM) algorithm and the refined segmentation is implemented with improved GrowCut (IGC) algorithm. The SKFCM algorithm introduces a kernel function and spatial constraint into fuzzy c-means clustering (FCM) algorithm. The IGC algorithm makes good use of the continuity of CT sequences in space which can automatically generate the seed labels and improve the efficiency of segmentation. The experimental results performed on the whole dataset of abdominal CT images have shown that the proposed method is accurate and efficient. The method provides a sensitivity of 95.46% with specificity of 99.82% and performs better than other related methods. CONCLUSIONS: Our method achieves high accuracy in kidney segmentation and considerably reduces the time and labor required for contour delineation. In addition, the method can be expanded to 3D segmentation directly without modification. PMID- 26356851 TI - Overexpression of miR-18a negatively regulates myocyte enhancer factor 2D to increase the permeability of the blood-tumor barrier via Kruppel-like factor 4 mediated downregulation of zonula occluden-1, claudin-5, and occludin. AB - miR-18a represses angiogenesis and tumor evasion by weakening vascular endothelial growth factor and transforming growth factor-beta signaling to prolong the survival of glioma patients, although it is thought to be an oncogene. This study investigates the potential effects of miR-18a on the permeability of the blood-tumor barrier (BTB) and its possible molecular mechanisms. An in vitro BTB model was successfully established. The endogenous expression of miR-18a in glioma vascular endothelial cells (GECs) was significantly lower than that in normal vascular ECs, and the overexpression of miR-18a significantly increased the permeability of the BTB as well as downregulating the mRNA and protein expressions of tight junction-related proteins zonula occluden-1 (ZO-1), claudin-5, and occludin in GECs. Dual luciferase reporter assays revealed that miR-18a bound to the 3'-untranslated region (3'UTR) of myocyte enhancer factor 2D (MEF2D). The overexpression of both miR-18a and MEF2D with the 3'UTR significantly weakened the effect caused by miR 18a of decreasing the mRNA and protein expressions of ZO-1, claudin-5 and occludin and of increasing the permeability of the BTB. Chromatin immunoprecipitation showed that MEF2D could directly bind to KLF4 promoter. This study shows that miR-18a targets and negatively regulates MEF2D, which further regulates tight junction-related proteins ZO-1, claudin-5, and occludin through transactivation of KLF4 and, finally, changes the permeability of the BTB. MiR 18a should garner growing attention because it might serve as a potential target in opening the BTB and providing a new strategy for the treatment of gliomas. PMID- 26356852 TI - Network-Based Drug-Target Interaction Prediction with Probabilistic Soft Logic. AB - Drug-target interaction studies are important because they can predict drugs' unexpected therapeutic or adverse side effects. In silico predictions of potential interactions are valuable and can focus effort on in vitro experiments. We propose a prediction framework that represents the problem using a bipartite graph of drug-target interactions augmented with drug-drug and target-target similarity measures and makes predictions using probabilistic soft logic (PSL). Using probabilistic rules in PSL, we predict interactions with models based on triad and tetrad structures. We apply (blocking) techniques that make link prediction in PSL more efficient for drug-target interaction prediction. We then perform extensive experimental studies to highlight different aspects of the model and the domain, first comparing the models with different structures and then measuring the effect of the proposed blocking on the prediction performance and efficiency. We demonstrate the importance of rule weight learning in the proposed PSL model and then show that PSL can effectively make use of a variety of similarity measures. We perform an experiment to validate the importance of collective inference and using multiple similarity measures for accurate predictions in contrast to non-collective and single similarity assumptions. Finally, we illustrate that our PSL model achieves state-of-the-art performance with simple, interpretable rules and evaluate our novel predictions using online data sets. PMID- 26356853 TI - Reliable Radiation Hybrid Maps: An Efficient Scalable Clustering-Based Approach. AB - The process of mapping markers from radiation hybrid mapping (RHM) experiments is equivalent to the traveling salesman problem and, thereby, has combinatorial complexity. As an additional problem, experiments typically result in some unreliable markers that reduce the overall quality of the map. We propose a clustering approach for addressing both problems efficiently by eliminating unreliable markers without the need for mapping the complete set of markers. Traditional approaches for eliminating markers use resampling of the full data set, which has an even higher computational complexity than the original mapping problem. In contrast, the proposed approach uses a divide-and-conquer strategy to construct framework maps based on clusters that exclude unreliable markers. Clusters are ordered using parallel processing and are then combined to form the complete map. We present three algorithms that explore the trade-off between the number of markers included in the map and placement accuracy. Using an RHM data set of the human genome, we compare the framework maps from our proposed approaches with published physical maps and with the results of using the Carthagene tool. Overall, our approaches have a very low computational complexity and produce solid framework maps with good chromosome coverage and high agreement with the physical map marker order. PMID- 26356854 TI - LateBiclustering: Efficient Heuristic Algorithm for Time-Lagged Bicluster Identification. AB - Identifying patterns in temporal data is key to uncover meaningful relationships in diverse domains, from stock trading to social interactions. Also of great interest are clinical and biological applications, namely monitoring patient response to treatment or characterizing activity at the molecular level. In biology, researchers seek to gain insight into gene functions and dynamics of biological processes, as well as potential perturbations of these leading to disease, through the study of patterns emerging from gene expression time series. Clustering can group genes exhibiting similar expression profiles, but focuses on global patterns denoting rather broad, unspecific responses. Biclustering reveals local patterns, which more naturally capture the intricate collaboration between biological players, particularly under a temporal setting. Despite the general biclustering formulation being NP-hard, considering specific properties of time series has led to efficient solutions for the discovery of temporally aligned patterns. Notably, the identification of biclusters with time-lagged patterns, suggestive of transcriptional cascades, remains a challenge due to the combinatorial explosion of delayed occurrences. Herein, we propose LateBiclustering, a sensible heuristic algorithm enabling a polynomial rather than exponential time solution for the problem. We show that it identifies meaningful time-lagged biclusters relevant to the response of Saccharomyces cerevisiae to heat stress. PMID- 26356855 TI - Discovery of Spatially Cohesive Itemsets in Three-Dimensional Protein Structures. AB - In this paper we present a cohesive structural itemset miner aiming to discover interesting patterns in a set of data objects within a multidimensional spatial structure by combining the cohesion and the support of the pattern. We propose two ways to build the itemset miner, VertexOne and VertexAll, in an attempt to find a balance between accuracy and run-times. The experiments show that VertexOne performs better, and finds almost the same itemsets as VertexAll in a much shorter time. The usefulness of the method is demonstrated by applying it to find interesting patterns of amino acids in spatial proximity within a set of proteins based on their atomic coordinates in the protein molecular structure. Several patterns found by the cohesive structural itemset miner contain amino acids that frequently co-occur in the spatial structure, even if they are distant in the primary protein sequence and only brought together by protein folding. Further various indications were found that some of the discovered patterns seem to represent common underlying support structures within the proteins. PMID- 26356856 TI - A Genomic Analysis Pipeline and Its Application to Pediatric Cancers. AB - We present a cancer genomic analysis pipeline which takes as input sequencing reads for both germline and tumor genomes and outputs filtered lists of all genetic mutations in the form of short ranked list of the most affected genes in the tumor, using either the Complete Genomics or Illumina platforms. A novel reporting and ranking system has been developed that makes use of publicly available datasets and literature specific to each patient, including new methods for using publicly available expression data in the absence of proper control data. Previously implicated small and large variations (including gene fusions) are reported in addition to probable driver mutations. Relationships between cancer and the sequenced tumor genome are highlighted using a network-based approach that integrates known and predicted protein-protein, protein-TF, and protein-drug interaction data. By using an integrative approach, effects of genetic variations on gene expression are used to provide further evidence of driver mutations. This pipeline has been developed with the aim to be used in assisting in the analysis of pediatric tumors, as an unbiased and automated method for interpreting sequencing results along with identifying potentially therapeutic drugs and their targets. We present results that agree with previous literature and highlight specific findings in a few patients. PMID- 26356857 TI - Accelerating the Next Generation Long Read Mapping with the FPGA-Based System. AB - To compare the newly determined sequences against the subject sequences stored in the databases is a critical job in the bioinformatics. Fortunately, recent survey reports that the state-of-the-art aligners are already fast enough to handle the ultra amount of short sequence reads in the reasonable time. However, for aligning the long sequence reads (>400 bp) generated by the next generation sequencing (NGS) technology, it is still quite inefficient with present aligners. Furthermore, the challenge becomes more and more serious as the lengths and the amounts of the sequence reads are both keeping increasing with the improvement of the sequencing technology. Thus, it is extremely urgent for the researchers to enhance the performance of the long read alignment. In this paper, we propose a novel FPGA-based system to improve the efficiency of the long read mapping. Compared to the state-of-the-art long read aligner BWA-SW, our accelerating platform could achieve a high performance with almost the same sensitivity. Experiments demonstrate that, for reads with lengths ranging from 512 up to 4,096 base pairs, the described system obtains a 10x -48x speedup for the bottleneck of the software. As to the whole mapping procedure, the FPGA-based platform could achieve a 1.8x -3:3x speedup versus the BWA-SW aligner, reducing the alignment cycles from weeks to days. PMID- 26356858 TI - acc-Motif: Accelerated Network Motif Detection. AB - Network motif algorithms have been a topic of research mainly after the 2002 seminal paper from Milo et al. [1], which provided motifs as a way to uncover the basic building blocks of most networks. Motifs have been mainly applied in Bioinformatics, regarding gene regulation networks. Motif detection is based on induced subgraph counting. This paper proposes an algorithm to count subgraphs of size k + 2 based on the set of induced subgraphs of size k. The general technique was applied to detect 3, 4 and 5-sized motifs in directed graphs. Such algorithms have time complexity O(a(G)m), O(m(2)) and O(nm(2)), respectively, where a(G) is the arboricity of G(V, E). The computational experiments in public data sets show that the proposed technique was one order of magnitude faster than Kavosh and FANMOD. When compared to NetMODE, acc-Motif had a slightly improved performance. PMID- 26356859 TI - Building Specific Signals from Frequency Chaos Game and Revealing Periodicities Using a Smoothed Fourier Analysis. AB - Investigating the roles and functions of DNA within genomes is becoming a primary focus of genomic research. Thus, the research works are moving towards cooperation between different scientific disciplines which aims at facilitating the interpretation of genetic information. In order to characterize the DNA of living organisms, signal processing tools appear to be very suitable for such study. However, a DNA sequence must be converted into a numerical sequence before processing; which defines the concept of DNA coding. In line with this, we propose a new one dimensional model based on the chaos game representation theory called Frequency Chaos Game Signal: FCGS. Then, we perform a Smoothed Fourier Transform to enhance hidden periodicities in the C.elegans DNA sequences. Through this study, we demonstrate the performance of our coding approach in highlighting characteristic periodicities. Indeed, several periodicities are shown to be involved in the 1D spectra and the 2D spectrograms of FCGSs. To investigate further about the contribution of our method in the enhancement of characteristic spectral attributes, a comparison with a range of binary indicators is established. PMID- 26356860 TI - Extended Graph-Based Models for Enhanced Similarity Search in Cavbase. AB - To calculate similarities between molecular structures, measures based on the maximum common subgraph are frequently applied. For the comparison of protein binding sites, these measures are not fully appropriate since graphs representing binding sites on a detailed atomic level tend to get very large. In combination with an NP-hard problem, a large graph leads to a computationally demanding task. Therefore, for the comparison of binding sites, a less detailed coarse graph model is used building upon so-called pseudocenters. Consistently, a loss of structural data is caused since many atoms are discarded and no information about the shape of the binding site is considered. This is usually resolved by performing subsequent calculations based on additional information. These steps are usually quite expensive, making the whole approach very slow. The main drawback of a graph-based model solely based on pseudocenters, however, is the loss of information about the shape of the protein surface. In this study, we propose a novel and efficient modeling formalism that does not increase the size of the graph model compared to the original approach, but leads to graphs containing considerably more information assigned to the nodes. More specifically, additional descriptors considering surface characteristics are extracted from the local surface and attributed to the pseudocenters stored in Cavbase. These properties are evaluated as additional node labels, which lead to a gain of information and allow for much faster but still very accurate comparisons between different structures. PMID- 26356861 TI - Genome-Wide Protein Function Prediction through Multi-Instance Multi-Label Learning. AB - Automated annotation of protein function is challenging. As the number of sequenced genomes rapidly grows, the vast majority of proteins can only be annotated computationally. Nature often brings several domains together to form multi-domain and multi-functional proteins with a vast number of possibilities, and each domain may fulfill its own function independently or in a concerted manner with its neighbors. Thus, it is evident that the protein function prediction problem is naturally and inherently Multi-Instance Multi-Label (MIML) learning tasks. Based on the state-of-the-art MIML algorithm MIMLNN, we propose a novel ensemble MIML learning framework EnMIMLNN and design three algorithms for this task by combining the advantage of three kinds of Hausdorff distance metrics. Experiments on seven real-world organisms covering the biological three domain system, i.e., archaea, bacteria, and eukaryote, show that the EnMIMLNN algorithms are superior to most state-of-the-art MIML and Multi-Label learning algorithms. PMID- 26356862 TI - iNJclust: Iterative Neighbor-Joining Tree Clustering Framework for Inferring Population Structure. AB - Understanding genetic differences among populations is one of the most important issues in population genetics. Genetic variations, e.g., single nucleotide polymorphisms, are used to characterize commonality and difference of individuals from various populations. This paper presents an efficient graph-based clustering framework which operates iteratively on the Neighbor-Joining (NJ) tree called the iNJclust algorithm. The framework uses well-known genetic measurements, namely the allele-sharing distance, the neighbor-joining tree, and the fixation index. The behavior of the fixation index is utilized in the algorithm's stopping criterion. The algorithm provides an estimated number of populations, individual assignments, and relationships between populations as outputs. The clustering result is reported in the form of a binary tree, whose terminal nodes represent the final inferred populations and the tree structure preserves the genetic relationships among them. The clustering performance and the robustness of the proposed algorithm are tested extensively using simulated and real data sets from bovine, sheep, and human populations. The result indicates that the number of populations within each data set is reasonably estimated, the individual assignment is robust, and the structure of the inferred population tree corresponds to the intrinsic relationships among populations within the data. PMID- 26356863 TI - Mining Conditional Phosphorylation Motifs. AB - Phosphorylation motifs represent position-specific amino acid patterns around the phosphorylation sites in the set of phosphopeptides. Several algorithms have been proposed to uncover phosphorylation motifs, whereas the problem of efficiently discovering a set of significant motifs with sufficiently high coverage and non redundancy still remains unsolved. Here we present a novel notion called conditional phosphorylation motifs. Through this new concept, the motifs whose over-expressiveness mainly benefits from its constituting parts can be filtered out effectively. To discover conditional phosphorylation motifs, we propose an algorithm called C-Motif for a non-redundant identification of significant phosphorylation motifs. C-Motif is implemented under the Apriori framework, and it tests the statistical significance together with the frequency of candidate motifs in a single stage. Experiments demonstrate that C-Motif outperforms some current algorithms such as MMFPh and Motif-All in terms of coverage and non redundancy of the results and efficiency of the execution. The source code of C Motif is available at: https://sourceforge. net/projects/cmotif/. PMID- 26356864 TI - Perfect Phylogeny Problems with Missing Values. AB - The perfect phylogeny problem is of central importance to both evolutionary biology and population genetics. Missing values are a common occurrence in both sequence and genotype data, but they make the problem of finding a perfect phylogeny NPhard even for binary characters. We introduce new and efficient perfect phylogeny algorithms for broad classes of binary and multistate data with missing values. Specifically, we address binary missing data consistent with the rich data hypothesis (RDH) introduced by Halperin and Karp and give an efficient algorithm for enumerating phylogenies. This algorithm is useful for computing the probability of data with missing values under the coalescent model. In addition, we use the partition intersection (PI) graph and chordal graph theory to generalize the RDH to multi-state characters with missing values. For a bounded number of states, we provide a fixed parameter tractable algorithm for the perfect phylogeny problem with missing data. Utilizing the PI graph, we are able to show that under multiple biologically motivated models for character data, our generalized RDH holds with high probability, and we evaluate our results with extensive empirical analysis. PMID- 26356865 TI - Similarity Measures for Comparing Biclusterings. AB - The comparison of ordinary partitions of a set of objects is well established in the clustering literature, which comprehends several studies on the analysis of the properties of similarity measures for comparing partitions. However, similarity measures for clusterings are not readily applicable to biclusterings, since each bicluster is a tuple of two sets (of rows and columns), whereas a cluster is only a single set (of rows). Some biclustering similarity measures have been defined as minor contributions in papers which primarily report on proposals and evaluation of biclustering algorithms or comparative analyses of biclustering algorithms. The consequence is that some desirable properties of such measures have been overlooked in the literature. We review 14 biclustering similarity measures. We define eight desirable properties of a biclustering measure, discuss their importance, and prove which properties each of the reviewed measures has. We show examples drawn and inspired from important studies in which several biclustering measures convey misleading evaluations due to the absence of one or more of the discussed properties. We also advocate the use of a more general comparison approach that is based on the idea of transforming the original problem of comparing biclusterings into an equivalent problem of comparing clustering partitions with overlapping clusters. PMID- 26356866 TI - Study of the Paired Change Points in Bacterial Genes. AB - It is known that nucleotide sequences are not totally homogeneous and this heterogeneity could not be due to random fluctuations only. Such heterogeneity poses a problem of making sequence segmentation into a set of homogeneous parts divided by the points called "change points". In this work we investigated a special case of change points-paired change points (PCP). We used a well-known property of coding sequences-triplet periodicity (TP). The sequences that we are especially interested in consist of three successive parts: the first and the last parts have similar TP while the middle part has different TP type. We aimed to find the genes with PCP and provide explanation for this phenomenon. We developed a mathematical method for the PCP detection based on the new measure of similarity between TP matrices. We investigated 66,936 bacterial genes from 17 bacterial genomes and revealed 2,700 genes with PCP and 6,459 genes with single change point (SCP). We developed a mathematical approach to visualize the PCP cases. We suppose that PCP could be associated with double fusion or insertion events. The results of investigating the sequences with artificial insertions/fusions and distribution of TP inside the genome support the idea that the real number of genes formed by insertion/ fusion events could be 5-7 times greater than the number of genes revealed in the present work. PMID- 26356867 TI - Synchronization of Boolean Networks with Different Update Schemes. AB - In this paper, the synchronizations of Boolean networks with different update schemes (synchronized Boolean networks and asynchronous Boolean networks) are investigated. All nodes in Boolean network are represented in terms of semi tensor product. First, we give the concept of inner synchronization and observe that all nodes in a Boolean network are synchronized with each other. Second, we investigate the outer synchronization between a driving Boolean network and a corresponding response Boolean network. We provide not only the concept of traditional complete synchronization, but also the anti-synchronization and get the anti-synchronization in simulation. Third, we extend the outer synchronization to asynchronous Boolean network and get the complete synchronization between an asynchronous Boolean network and a response Boolean network. Consequently, theorems for synchronization of Boolean networks and asynchronous Boolean networks are derived. Examples are provided to show the correctness of our theorems. PMID- 26356868 TI - RNA-Seq Analysis Pipeline Based on Oshell Environment. AB - Advances in transcriptome sequencing (RNA-Seq) have revolutionized the way to characterize and quantify transcripts. The breakthroughs in RNA-Seq technologies give rise to the ever-increasing volumes of data, making data processing the bottleneck of transcriptome research. It becomes crucial to develop an efficient analysis pipeline to automate RNA-Seq data analysis. Based on Oshell environment, we present here an ultra-fast and powerful RNA-Seq analysis pipeline for quality control, sequence alignment, variation detection, expression quantification and junction discovery. The pipeline runs on both Linux and Windows operating systems, with either stand-alone or cluster computing environment. Parallel computing is also supported for improved processing speed. Oshell is free for non commercial use at http://omicsoft.com/oshell. PMID- 26356869 TI - Examining the cause of high inbreeding depression: analysis of whole-genome sequence data in 28 selfed progeny of Eucalyptus grandis. AB - The genome-wide heterozygosity at 9590 genes, all heterozygous in a single Eucalyptus grandis parent tree, was examined in a group of 28 S1 offspring. Heterozygosity ranged from 52-79%, averaging 65.5%, much higher than the 50% expected under random segregation, supporting the occurrence of strong (47%) selection against homozygosity. The expected pattern of heterozygosity from theoretical calculations and simulations for recessive detrimentals (pseudo overdominance) and intrinsic heterozygote advantage was examined and compared with that observed. The observed patterns are consistent with at least several detrimental loci with large effects on both parental chromosomes of the 11 pairs. It is likely that 100 or more genes, many with substantial effects on viability, are contributing to this inbreeding depression. Although our genome-wide analysis of nearly 10 000 genes strongly suggested that pseudo-overdominance was responsible for the observed high inbreeding depression, heterozygote advantage could not be excluded. Finding inconvertible evidence of the cause of inbreeding depression still presents a difficult challenge. This study is the first theoretical examination of the genomic effect of inbreeding in a forest tree and provides an approach to analyze these data to determine the extent and cause of inbreeding depression across other plant genomes. PMID- 26356870 TI - Groundwater Modeling with MODFLOW as a Web Application. PMID- 26356871 TI - Considerations Left behind Middle East Respiratory Syndrome Coronavirus (MERS CoV) Outbreaks in Republic of Korea. PMID- 26356872 TI - Mesenchymal Bone Marrow-derived Stem Cells Transplantation in Patients with HCV Related Liver Cirrhosis. AB - BACKGROUND AND AIMS: To evaluate the effect of intraparenchymal transplantation of mesenchymal bone marrow-derived stem cells (BMSCs) in patients with hepatitis C virus (HCV)-related liver cirrhosis (LC). METHODS: Mononuclear cells were isolated from patient bone marrow and were passaged several times in vitro in order to reach the required volume. Attributes of the BMSCs were evaluated by the presence of the surface markers CD105+, CD90+, and CD73+. Cells from each passage were evaluated for sterility, and they were transplanted intraparenchymally into liver tissue. Clinical and laboratory data were evaluated and morphological studies of liver biopsy were performed prior to and 6 months after transplantation. RESULTS: On clinical evaluation, the general state of these patients was improved at 1 month following transplantation of BMSCs. At 1 and 6 months post-transplantation, jaundice was absent in four (67%) patients. After 6 months, functional hepatic indices were improved, i.e. decrease of ALT and AST activity and bilirubin level. However, these decreases were not statistically different (P>0.05). Expression of CD34 and alpha-SMA in liver biopsy samples were decreased at 6 months after transplantation, consistent with structural improvements in mitochondria and nuclear compartments. CONCLUSIONS: Intraparenchymal transplantation of autologous BMSCs improved the functional condition of the liver, stimulated reparative processes in hepatocytes, and decreased extracellular matrix protein (EMP) count in hepatic tissues of patients with LC. It was well tolerated and was not associated with any complications both during and after BMSC transplantation. PMID- 26356873 TI - tBuLi-Mediated One-Pot Direct Highly Selective Cross-Coupling of Two Distinct Aryl Bromides. AB - A Pd-catalyzed direct cross-coupling of two distinct aryl bromides mediated by tBuLi is described. The use of [Pd-PEPPSI-IPr] or [Pd-PEPPSI-IPent] as catalyst allows for the efficient one-pot synthesis of unsymmetrical biaryls at room temperature. The key for this selective cross-coupling is the use of an ortho substituted bromide that undergoes lithium-halogen exchange preferentially. PMID- 26356874 TI - Knowledge Generation Model for Visual Analytics. AB - Visual analytics enables us to analyze huge information spaces in order to support complex decision making and data exploration. Humans play a central role in generating knowledge from the snippets of evidence emerging from visual data analysis. Although prior research provides frameworks that generalize this process, their scope is often narrowly focused so they do not encompass different perspectives at different levels. This paper proposes a knowledge generation model for visual analytics that ties together these diverse frameworks, yet retains previously developed models (e.g., KDD process) to describe individual segments of the overall visual analytic processes. To test its utility, a real world visual analytics system is compared against the model, demonstrating that the knowledge generation process model provides a useful guideline when developing and evaluating such systems. The model is used to effectively compare different data analysis systems. Furthermore, the model provides a common language and description of visual analytic processes, which can be used for communication between researchers. At the end, our model reflects areas of research that future researchers can embark on. PMID- 26356875 TI - INFUSE: Interactive Feature Selection for Predictive Modeling of High Dimensional Data. AB - Predictive modeling techniques are increasingly being used by data scientists to understand the probability of predicted outcomes. However, for data that is high dimensional, a critical step in predictive modeling is determining which features should be included in the models. Feature selection algorithms are often used to remove non-informative features from models. However, there are many different classes of feature selection algorithms. Deciding which one to use is problematic as the algorithmic output is often not amenable to user interpretation. This limits the ability for users to utilize their domain expertise during the modeling process. To improve on this limitation, we developed INFUSE, a novel visual analytics system designed to help analysts understand how predictive features are being ranked across feature selection algorithms, cross-validation folds, and classifiers. We demonstrate how our system can lead to important insights in a case study involving clinical researchers predicting patient outcomes from electronic medical records. PMID- 26356876 TI - Transforming Scagnostics to Reveal Hidden Features. AB - Scagnostics (Scatterplot Diagnostics) were developed by Wilkinson et al. based on an idea of Paul and John Tukey, in order to discern meaningful patterns in large collections of scatterplots. The Tukeys' original idea was intended to overcome the impediments involved in examining large scatterplot matrices (multiplicity of plots and lack of detail). Wilkinson's implementation enabled for the first time scagnostics computations on many points as well as many plots. Unfortunately, scagnostics are sensitive to scale transformations. We illustrate the extent of this sensitivity and show how it is possible to pair statistical transformations with scagnostics to enable discovery of hidden structures in data that are not discernible in untransformed visualizations. PMID- 26356877 TI - Supporting Communication and Coordination in Collaborative Sensemaking. AB - When people work together to analyze a data set, they need to organize their findings, hypotheses, and evidence, share that information with their collaborators, and coordinate activities amongst team members. Sharing externalizations (recorded information such as notes) could increase awareness and assist with team communication and coordination. However, we currently know little about how to provide tool support for this sort of sharing. We explore how linked common work (LCW) can be employed within a 'collaborative thinking space', to facilitate synchronous collaborative sensemaking activities in Visual Analytics (VA). Collaborative thinking spaces provide an environment for analysts to record, organize, share and connect externalizations. Our tool, CLIP, extends earlier thinking spaces by integrating LCW features that reveal relationships between collaborators' findings. We conducted a user study comparing CLIP to a baseline version without LCW. Results demonstrated that LCW significantly improved analytic outcomes at a collaborative intelligence task. Groups using CLIP were also able to more effectively coordinate their work, and held more discussion of their findings and hypotheses. LCW enabled them to maintain awareness of each other's activities and findings and link those findings to their own work, preventing disruptive oral awareness notifications. PMID- 26356878 TI - Opening the Black Box: Strategies for Increased User Involvement in Existing Algorithm Implementations. AB - An increasing number of interactive visualization tools stress the integration with computational software like MATLAB and R to access a variety of proven algorithms. In many cases, however, the algorithms are used as black boxes that run to completion in isolation which contradicts the needs of interactive data exploration. This paper structures, formalizes, and discusses possibilities to enable user involvement in ongoing computations. Based on a structured characterization of needs regarding intermediate feedback and control, the main contribution is a formalization and comparison of strategies for achieving user involvement for algorithms with different characteristics. In the context of integration, we describe considerations for implementing these strategies either as part of the visualization tool or as part of the algorithm, and we identify requirements and guidelines for the design of algorithmic APIs. To assess the practical applicability, we provide a survey of frequently used algorithm implementations within R regarding the fulfillment of these guidelines. While echoing previous calls for analysis modules which support data exploration more directly, we conclude that a range of pragmatic options for enabling user involvement in ongoing computations exists on both the visualization and algorithm side and should be used. PMID- 26356879 TI - Progressive Visual Analytics: User-Driven Visual Exploration of In-Progress Analytics. AB - As datasets grow and analytic algorithms become more complex, the typical workflow of analysts launching an analytic, waiting for it to complete, inspecting the results, and then re-Iaunching the computation with adjusted parameters is not realistic for many real-world tasks. This paper presents an alternative workflow, progressive visual analytics, which enables an analyst to inspect partial results of an algorithm as they become available and interact with the algorithm to prioritize subspaces of interest. Progressive visual analytics depends on adapting analytical algorithms to produce meaningful partial results and enable analyst intervention without sacrificing computational speed. The paradigm also depends on adapting information visualization techniques to incorporate the constantly refining results without overwhelming analysts and provide interactions to support an analyst directing the analytic. The contributions of this paper include: a description of the progressive visual analytics paradigm; design goals for both the algorithms and visualizations in progressive visual analytics systems; an example progressive visual analytics system (Progressive Insights) for analyzing common patterns in a collection of event sequences; and an evaluation of Progressive Insights and the progressive visual analytics paradigm by clinical researchers analyzing electronic medical records. PMID- 26356880 TI - Finding Waldo: Learning about Users from their Interactions. AB - Visual analytics is inherently a collaboration between human and computer. However, in current visual analytics systems, the computer has limited means of knowing about its users and their analysis processes. While existing research has shown that a user's interactions with a system reflect a large amount of the user's reasoning process, there has been limited advancement in developing automated, real-time techniques that mine interactions to learn about the user. In this paper, we demonstrate that we can accurately predict a user's task performance and infer some user personality traits by using machine learning techniques to analyze interaction data. Specifically, we conduct an experiment in which participants perform a visual search task, and apply well-known machine learning algorithms to three encodings of the users' interaction data. We achieve, depending on algorithm and encoding, between 62% and 83% accuracy at predicting whether each user will be fast or slow at completing the task. Beyond predicting performance, we demonstrate that using the same techniques, we can infer aspects of the user's personality factors, including locus of control, extraversion, and neuroticism. Further analyses show that strong results can be attained with limited observation time: in one case 95% of the final accuracy is gained after a quarter of the average task completion time. Overall, our findings show that interactions can provide information to the computer about its human collaborator, and establish a foundation for realizing mixed-initiative visual analytics systems. PMID- 26356881 TI - Interactive Visual Analysis of Image-Centric Cohort Study Data. AB - Epidemiological population studies impose information about a set of subjects (a cohort) to characterize disease-specific risk factors. Cohort studies comprise heterogenous variables describing the medical condition as well as demographic and lifestyle factors and, more recently, medical image data. We propose an Interactive Visual Analysis (IVA) approach that enables epidemiologists to rapidly investigate the entire data pool for hypothesis validation and generation. We incorporate image data, which involves shape-based object detection and the derivation of attributes describing the object shape. The concurrent investigation of image-based and non-image data is realized in a web based multiple coordinated view system, comprising standard views from information visualization and epidemiological data representations such as pivot tables. The views are equipped with brushing facilities and augmented by 3D shape renderings of the segmented objects, e.g., each bar in a histogram is overlaid with a mean shape of the associated subgroup of the cohort. We integrate an overview visualization, clustering of variables and object shape for data-driven subgroup definition and statistical key figures for measuring the association between variables. We demonstrate the IVA approach by validating and generating hypotheses related to lower back pain as part of a qualitative evaluation. PMID- 26356882 TI - Visual Abstraction and Exploration of Multi-class Scatterplots. AB - Scatterplots are widely used to visualize scatter dataset for exploring outliers, clusters, local trends, and correlations. Depicting multi-class scattered points within a single scatterplot view, however, may suffer from heavy overdraw, making it inefficient for data analysis. This paper presents a new visual abstraction scheme that employs a hierarchical multi-class sampling technique to show a feature-preserving simplification. To enhance the density contrast, the colors of multiple classes are optimized by taking the multi-class point distributions into account. We design a visual exploration system that supports visual inspection and quantitative analysis from different perspectives. We have applied our system to several challenging datasets, and the results demonstrate the efficiency of our approach. PMID- 26356883 TI - Cupid: Cluster-Based Exploration of Geometry Generators with Parallel Coordinates and Radial Trees. AB - Geometry generators are commonly used in video games and evaluation systems for computer vision to create geometric shapes such as terrains, vegetation or airplanes. The parameters of the generator are often sampled automatically which can lead to many similar or unwanted geometric shapes. In this paper, we propose a novel visual exploration approach that combines the abstract parameter space of the geometry generator with the resulting 3D shapes in a composite visualization. Similar geometric shapes are first grouped using hierarchical clustering and then nested within an illustrative parallel coordinates visualization. This helps the user to study the sensitivity of the generator with respect to its parameter space and to identify invalid parameter settings. Starting from a compact overview representation, the user can iteratively drill-down into local shape differences by clicking on the respective clusters. Additionally, a linked radial tree gives an overview of the cluster hierarchy and enables the user to manually split or merge clusters. We evaluate our approach by exploring the parameter space of a cup generator and provide feedback from domain experts. PMID- 26356884 TI - Visual Methods for Analyzing Probabilistic Classification Data. AB - Multi-class classifiers often compute scores for the classification samples describing probabilities to belong to different classes. In order to improve the performance of such classifiers, machine learning experts need to analyze classification results for a large number of labeled samples to find possible reasons for incorrect classification. Confusion matrices are widely used for this purpose. However, they provide no information about classification scores and features computed for the samples. We propose a set of integrated visual methods for analyzing the performance of probabilistic classifiers. Our methods provide insight into different aspects of the classification results for a large number of samples. One visualization emphasizes at which probabilities these samples were classified and how these probabilities correlate with classification error in terms of false positives and false negatives. Another view emphasizes the features of these samples and ranks them by their separation power between selected true and false classifications. We demonstrate the insight gained using our technique in a benchmarking classification dataset, and show how it enables improving classification performance by interactively defining and evaluating post-classification rules. PMID- 26356885 TI - A Five-Level Design Framework for Bicluster Visualizations. AB - Analysts often need to explore and identify coordinated relationships (e.g., four people who visited the same five cities on the same set of days) within some large datasets for sensemaking. Biclusters provide a potential solution to ease this process, because each computed bicluster bundles individual relationships into coordinated sets. By understanding such computed, structural, relations within biclusters, analysts can leverage their domain knowledge and intuition to determine the importance and relevance of the extracted relationships for making hypotheses. However, due to the lack of systematic design guidelines, it is still a challenge to design effective and usable visualizations of biclusters to enhance their perceptibility and interactivity for exploring coordinated relationships. In this paper, we present a five-level design framework for bicluster visualizations, with a survey of the state-of-the-art design considerations and applications that are related or that can be applied to bicluster visualizations. We summarize pros and cons of these design options to support user tasks at each of the five-level relationships. Finally, we discuss future research challenges for bicluster visualizations and their incorporation into visual analytics tools. PMID- 26356886 TI - VarifocalReader--In-Depth Visual Analysis of Large Text Documents. AB - Interactive visualization provides valuable support for exploring, analyzing, and understanding textual documents. Certain tasks, however, require that insights derived from visual abstractions are verified by a human expert perusing the source text. So far, this problem is typically solved by offering overview-detail techniques, which present different views with different levels of abstractions. This often leads to problems with visual continuity. Focus-context techniques, on the other hand, succeed in accentuating interesting subsections of large text documents but are normally not suited for integrating visual abstractions. With VarifocalReader we present a technique that helps to solve some of these approaches' problems by combining characteristics from both. In particular, our method simplifies working with large and potentially complex text documents by simultaneously offering abstract representations of varying detail, based on the inherent structure of the document, and access to the text itself. In addition, VarifocalReader supports intra-document exploration through advanced navigation concepts and facilitates visual analysis tasks. The approach enables users to apply machine learning techniques and search mechanisms as well as to assess and adapt these techniques. This helps to extract entities, concepts and other artifacts from texts. In combination with the automatic generation of intermediate text levels through topic segmentation for thematic orientation, users can test hypotheses or develop interesting new research questions. To illustrate the advantages of our approach, we provide usage examples from literature studies. PMID- 26356887 TI - LoyalTracker: Visualizing Loyalty Dynamics in Search Engines. AB - The huge amount of user log data collected by search engine providers creates new opportunities to understand user loyalty and defection behavior at an unprecedented scale. However, this also poses a great challenge to analyze the behavior and glean insights into the complex, large data. In this paper, we introduce LoyalTracker, a visual analytics system to track user loyalty and switching behavior towards multiple search engines from the vast amount of user log data. We propose a new interactive visualization technique (flow view) based on a flow metaphor, which conveys a proper visual summary of the dynamics of user loyalty of thousands of users over time. Two other visualization techniques, a density map and a word cloud, are integrated to enable analysts to gain further insights into the patterns identified by the flow view. Case studies and the interview with domain experts are conducted to demonstrate the usefulness of our technique in understanding user loyalty and switching behavior in search engines. PMID- 26356888 TI - VAET: A Visual Analytics Approach for E-Transactions Time-Series. AB - Previous studies on E-transaction time-series have mainly focused on finding temporal trends of transaction behavior. Interesting transactions that are time stamped and situation-relevant may easily be obscured in a large amount of information. This paper proposes a visual analytics system, Visual Analysis of E transaction Time-Series (VAET), that allows the analysts to interactively explore large transaction datasets for insights about time-varying transactions. With a set of analyst-determined training samples, VAET automatically estimates the saliency of each transaction in a large time-series using a probabilistic decision tree learner. It provides an effective time-of-saliency (TOS) map where the analysts can explore a large number of transactions at different time granularities. Interesting transactions are further encoded with KnotLines, a compact visual representation that captures both the temporal variations and the contextual connection of transactions. The analysts can thus explore, select, and investigate knotlines of interest. A case study and user study with a real E transactions dataset (26 million records) demonstrate the effectiveness of VAET. PMID- 26356889 TI - EvoRiver: Visual Analysis of Topic Coopetition on Social Media. AB - Cooperation and competition (jointly called "coopetition") are two modes of interactions among a set of concurrent topics on social media. How do topics cooperate or compete with each other to gain public attention? Which topics tend to cooperate or compete with one another? Who plays the key role in coopetition related interactions? We answer these intricate questions by proposing a visual analytics system that facilitates the in-depth analysis of topic coopetition on social media. We model the complex interactions among topics as a combination of carry-over, coopetition recruitment, and coopetition distraction effects. This model provides a close functional approximation of the coopetition process by depicting how different groups of influential users (i.e., "topic leaders") affect coopetition. We also design EvoRiver, a time-based visualization, that allows users to explore coopetition-related interactions and to detect dynamically evolving patterns, as well as their major causes. We test our model and demonstrate the usefulness of our system based on two Twitter data sets (social topics data and business topics data). PMID- 26356890 TI - OpinionFlow: Visual Analysis of Opinion Diffusion on Social Media. AB - It is important for many different applications such as government and business intelligence to analyze and explore the diffusion of public opinions on social media. However, the rapid propagation and great diversity of public opinions on social media pose great challenges to effective analysis of opinion diffusion. In this paper, we introduce a visual analysis system called OpinionFlow to empower analysts to detect opinion propagation patterns and glean insights. Inspired by the information diffusion model and the theory of selective exposure, we develop an opinion diffusion model to approximate opinion propagation among Twitter users. Accordingly, we design an opinion flow visualization that combines a Sankey graph with a tailored density map in one view to visually convey diffusion of opinions among many users. A stacked tree is used to allow analysts to select topics of interest at different levels. The stacked tree is synchronized with the opinion flow visualization to help users examine and compare diffusion patterns across topics. Experiments and case studies on Twitter data demonstrate the effectiveness and usability of OpinionFlow. PMID- 26356891 TI - #FluxFlow: Visual Analysis of Anomalous Information Spreading on Social Media. AB - We present FluxFlow, an interactive visual analysis system for revealing and analyzing anomalous information spreading in social media. Everyday, millions of messages are created, commented, and shared by people on social media websites, such as Twitter and Facebook. This provides valuable data for researchers and practitioners in many application domains, such as marketing, to inform decision making. Distilling valuable social signals from the huge crowd's messages, however, is challenging, due to the heterogeneous and dynamic crowd behaviors. The challenge is rooted in data analysts' capability of discerning the anomalous information behaviors, such as the spreading of rumors or misinformation, from the rest that are more conventional patterns, such as popular topics and newsworthy events, in a timely fashion. FluxFlow incorporates advanced machine learning algorithms to detect anomalies, and offers a set of novel visualization designs for presenting the detected threads for deeper analysis. We evaluated FluxFlow with real datasets containing the Twitter feeds captured during significant events such as Hurricane Sandy. Through quantitative measurements of the algorithmic performance and qualitative interviews with domain experts, the results show that the back-end anomaly detection model is effective in identifying anomalous retweeting threads, and its front-end interactive visualizations are intuitive and useful for analysts to discover insights in data and comprehend the underlying analytical model. PMID- 26356892 TI - DecisionFlow: Visual Analytics for High-Dimensional Temporal Event Sequence Data. AB - Temporal event sequence data is increasingly commonplace, with applications ranging from electronic medical records to financial transactions to social media activity. Previously developed techniques have focused on low-dimensional datasets (e.g., with less than 20 distinct event types). Real-world datasets are often far more complex. This paper describes DecisionFlow, a visual analysis technique designed to support the analysis of high-dimensional temporal event sequence data (e.g., thousands of event types). DecisionFlow combines a scalable and dynamic temporal event data structure with interactive multi-view visualizations and ad hoc statistical analytics. We provide a detailed review of our methods, and present the results from a 12-person user study. The study results demonstrate that DecisionFlow enables the quick and accurate completion of a range of sequence analysis tasks for datasets containing thousands of event types and millions of individual events. PMID- 26356893 TI - Footprints: A Visual Search Tool that Supports Discovery and Coverage Tracking. AB - Searching a large document collection to learn about a broad subject involves the iterative process of figuring out what to ask, filtering the results, identifying useful documents, and deciding when one has covered enough material to stop searching. We are calling this activity "discoverage," discovery of relevant material and tracking coverage of that material. We built a visual analytic tool called Footprints that uses multiple coordinated visualizations to help users navigate through the discoverage process. To support discovery, Footprints displays topics extracted from documents that provide an overview of the search space and are used to construct searches visuospatially. Footprints allows users to triage their search results by assigning a status to each document (To Read, Read, Useful), and those status markings are shown on interactive histograms depicting the user's coverage through the documents across dates, sources, and topics. Coverage histograms help users notice biases in their search and fill any gaps in their analytic process. To create Footprints, we used a highly iterative, user-centered approach in which we conducted many evaluations during both the design and implementation stages and continually modified the design in response to feedback. PMID- 26356894 TI - Visual Analytics for Complex Engineering Systems: Hybrid Visual Steering of Simulation Ensembles. AB - In this paper we propose a novel approach to hybrid visual steering of simulation ensembles. A simulation ensemble is a collection of simulation runs of the same simulation model using different sets of control parameters. Complex engineering systems have very large parameter spaces so a naive sampling can result in prohibitively large simulation ensembles. Interactive steering of simulation ensembles provides the means to select relevant points in a multi-dimensional parameter space (design of experiment). Interactive steering efficiently reduces the number of simulation runs needed by coupling simulation and visualization and allowing a user to request new simulations on the fly. As system complexity grows, a pure interactive solution is not always sufficient. The new approach of hybrid steering combines interactive visual steering with automatic optimization. Hybrid steering allows a domain expert to interactively (in a visualization) select data points in an iterative manner, approximate the values in a continuous region of the simulation space (by regression) and automatically find the "best" points in this continuous region based on the specified constraints and objectives (by optimization). We argue that with the full spectrum of optimization options, the steering process can be improved substantially. We describe an integrated system consisting of a simulation, a visualization, and an optimization component. We also describe typical tasks and propose an interactive analysis workflow for complex engineering systems. We demonstrate our approach on a case study from automotive industry, the optimization of a hydraulic circuit in a high pressure common rail Diesel injection system. PMID- 26356895 TI - Visual Exploration of Sparse Traffic Trajectory Data. AB - In this paper, we present a visual analysis system to explore sparse traffic trajectory data recorded by transportation cells. Such data contains the movements of nearly all moving vehicles on the major roads of a city. Therefore it is very suitable for macro-traffic analysis. However, the vehicle movements are recorded only when they pass through the cells. The exact tracks between two consecutive cells are unknown. To deal with such uncertainties, we first design a local animation, showing the vehicle movements only in the vicinity of cells. Besides, we ignore the micro-behaviors of individual vehicles, and focus on the macro-traffic patterns. We apply existing trajectory aggregation techniques to the dataset, studying cell status pattern and inter-cell flow pattern. Beyond that, we propose to study the correlation between these two patterns with dynamic graph visualization techniques. It allows us to check how traffic congestion on one cell is correlated with traffic flows on neighbouring links, and with route selection in its neighbourhood. Case studies show the effectiveness of our system. PMID- 26356896 TI - DIA2: Web-based Cyberinfrastructure for Visual Analysis of Funding Portfolios. AB - We present a design study of the Deep Insights Anywhere, Anytime (DIA2) platform, a web-based visual analytics system that allows program managers and academic staff at the U.S. National Science Foundation to search, view, and analyze their research funding portfolio. The goal of this system is to facilitate users' understanding of both past and currently active research awards in order to make more informed decisions of their future funding. This user group is characterized by high domain expertise yet not necessarily high literacy in visualization and visual analytics-they are essentially casual experts-and thus require careful visual and information design, including adhering to user experience standards, providing a self-instructive interface, and progressively refining visualizations to minimize complexity. We discuss the challenges of designing a system for casual experts and highlight how we addressed this issue by modeling the organizational structure and workflows of the NSF within our system. We discuss each stage of the design process, starting with formative interviews, prototypes, and finally live deployments and evaluation with stakeholders. PMID- 26356897 TI - Visualizing Mobility of Public Transportation System. AB - Public transportation systems (PTSs) play an important role in modern cities, providing shared/massive transportation services that are essential for the general public. However, due to their increasing complexity, designing effective methods to visualize and explore PTS is highly challenging. Most existing techniques employ network visualization methods and focus on showing the network topology across stops while ignoring various mobility-related factors such as riding time, transfer time, waiting time, and round-the-clock patterns. This work aims to visualize and explore passenger mobility in a PTS with a family of analytical tasks based on inputs from transportation researchers. After exploring different design alternatives, we come up with an integrated solution with three visualization modules: isochrone map view for geographical information, isotime flow map view for effective temporal information comparison and manipulation, and OD-pair journey view for detailed visual analysis of mobility factors along routes between specific origin-destination pairs. The isotime flow map linearizes a flow map into a parallel isoline representation, maximizing the visualization of mobility information along the horizontal time axis while presenting clear and smooth pathways from origin to destinations. Moreover, we devise several interactive visual query methods for users to easily explore the dynamics of PTS mobility over space and time. Lastly, we also construct a PTS mobility model from millions of real passenger trajectories, and evaluate our visualization techniques with assorted case studies with the transportation researchers. PMID- 26356898 TI - Visual Analysis of Public Utility Service Problems in a Metropolis. AB - Issues about city utility services reported by citizens can provide unprecedented insights into the various aspects of such services. Analysis of these issues can improve living quality through evidence-based decision making. However, these issues are complex, because of the involvement of spatial and temporal components, in addition to having multi-dimensional and multivariate natures. Consequently, exploring utility service problems and creating visual representations are difficult. To analyze these issues, we propose a visual analytics process based on the main tasks of utility service management. We also propose an aggregate method that transforms numerous issues into legible events and provide visualizations for events. In addition, we provide a set of tools and interaction techniques to explore such issues. Our approach enables administrators to make more informed decisions. PMID- 26356900 TI - Proactive Spatiotemporal Resource Allocation and Predictive Visual Analytics for Community Policing and Law Enforcement. AB - In this paper, we present a visual analytics approach that provides decision makers with a proactive and predictive environment in order to assist them in making effective resource allocation and deployment decisions. The challenges involved with such predictive analytics processes include end-users' understanding, and the application of the underlying statistical algorithms at the right spatiotemporal granularity levels so that good prediction estimates can be established. In our approach, we provide analysts with a suite of natural scale templates and methods that enable them to focus and drill down to appropriate geospatial and temporal resolution levels. Our forecasting technique is based on the Seasonal Trend decomposition based on Loess (STL) method, which we apply in a spatiotemporal visual analytics context to provide analysts with predicted levels of future activity. We also present a novel kernel density estimation technique we have developed, in which the prediction process is influenced by the spatial correlation of recent incidents at nearby locations. We demonstrate our techniques by applying our methodology to Criminal, Traffic and Civil (CTC) incident datasets. PMID- 26356899 TI - VASA: Interactive Computational Steering of Large Asynchronous Simulation Pipelines for Societal Infrastructure. AB - We present VASA, a visual analytics platform consisting of a desktop application, a component model, and a suite of distributed simulation components for modeling the impact of societal threats such as weather, food contamination, and traffic on critical infrastructure such as supply chains, road networks, and power grids. Each component encapsulates a high-fidelity simulation model that together form an asynchronous simulation pipeline: a system of systems of individual simulations with a common data and parameter exchange format. At the heart of VASA is the Workbench, a visual analytics application providing three distinct features: (1) low-fidelity approximations of the distributed simulation components using local simulation proxies to enable analysts to interactively configure a simulation run; (2) computational steering mechanisms to manage the execution of individual simulation components; and (3) spatiotemporal and interactive methods to explore the combined results of a simulation run. We showcase the utility of the platform using examples involving supply chains during a hurricane as well as food contamination in a fast food restaurant chain. PMID- 26356901 TI - Run Watchers: Automatic Simulation-Based Decision Support in Flood Management. AB - In this paper, we introduce a simulation-based approach to design protection plans for flood events. Existing solutions require a lot of computation time for an exhaustive search, or demand for a time-consuming expert supervision and steering. We present a faster alternative based on the automated control of multiple parallel simulation runs. Run Watchers are dedicated system components authorized to monitor simulation runs, terminate them, and start new runs originating from existing ones according to domain-specific rules. This approach allows for a more efficient traversal of the search space and overall performance improvements due to a re-use of simulated states and early termination of failed runs. In the course of search, Run Watchers generate large and complex decision trees. We visualize the entire set of decisions made by Run Watchers using interactive, clustered timelines. In addition, we present visualizations to explain the resulting response plans. Run Watchers automatically generate storyboards to convey plan details and to justify the underlying decisions, including those which leave particular buildings unprotected. We evaluate our solution with domain experts. PMID- 26356902 TI - ConTour: Data-Driven Exploration of Multi-Relational Datasets for Drug Discovery. AB - Large scale data analysis is nowadays a crucial part of drug discovery. Biologists and chemists need to quickly explore and evaluate potentially effective yet safe compounds based on many datasets that are in relationship with each other. However, there is a lack of tools that support them in these processes. To remedy this, we developed ConTour, an interactive visual analytics technique that enables the exploration of these complex, multi-relational datasets. At its core ConTour lists all items of each dataset in a column. Relationships between the columns are revealed through interaction: selecting one or multiple items in one column highlights and re-sorts the items in other columns. Filters based on relationships enable drilling down into the large data space. To identify interesting items in the first place, ConTour employs advanced sorting strategies, including strategies based on connectivity strength and uniqueness, as well as sorting based on item attributes. ConTour also introduces interactive nesting of columns, a powerful method to show the related items of a child column for each item in the parent column. Within the columns, ConTour shows rich attribute data about the items as well as information about the connection strengths to other datasets. Finally, ConTour provides a number of detail views, which can show items from multiple datasets and their associated data at the same time. We demonstrate the utility of our system in case studies conducted with a team of chemical biologists, who investigate the effects of chemical compounds on cells and need to understand the underlying mechanisms. PMID- 26356903 TI - Visual Analytics for Comparison of Ocean Model Output with Reference Data: Detecting and Analyzing Geophysical Processes Using Clustering Ensembles. AB - Researchers assess the quality of an ocean model by comparing its output to that of a previous model version or to observations. One objective of the comparison is to detect and to analyze differences and similarities between both data sets regarding geophysical processes, such as particular ocean currents. This task involves the analysis of thousands or hundreds of thousands of geographically referenced temporal profiles in the data. To cope with the amount of data, modelers combine aggregation of temporal profiles to single statistical values with visual comparison. Although this strategy is based on experience and a well grounded body of expert knowledge, our discussions with domain experts have shown that it has two limitations: (1) using a single statistical measure results in a rather limited scope of the comparison and in significant loss of information, and (2) the decisions modelers have to make in the process may lead to important aspects being overlooked. In this article, we propose a Visual Analytics approach that broadens the scope of the analysis, reduces subjectivity, and facilitates comparison of the two data sets. It comprises three steps: First, it allows modelers to consider many aspects of the temporal behavior of geophysical processes by conducting multiple clusterings of the temporal profiles in each data set. Modelers can choose different features describing the temporal behavior of relevant processes, clustering algorithms, and parameterizations. Second, our approach consolidates the clusterings of one data set into a single clustering via a clustering ensembles approach. The consolidated clustering presents an overview of the geospatial distribution of temporal behavior in a data set. Third, a visual interface allows modelers to compare the two consolidated clusterings. It enables them to detect clusters of temporal profiles that represent geophysical processes and to analyze differences and similarities between two data sets. This work is the result of a close collaboration with ocean modelers. They employed our concept to find aspects of improvement in a new version of the Ocean Model for Circulation and Tides (OMCT). PMID- 26356904 TI - Genotet: An Interactive Web-based Visual Exploration Framework to Support Validation of Gene Regulatory Networks. AB - Elucidation of transcriptional regulatory networks (TRNs) is a fundamental goal in biology, and one of the most important components of TRNs are transcription factors (TFs), proteins that specifically bind to gene promoter and enhancer regions to alter target gene expression patterns. Advances in genomic technologies as well as advances in computational biology have led to multiple large regulatory network models (directed networks) each with a large corpus of supporting data and gene-annotation. There are multiple possible biological motivations for exploring large regulatory network models, including: validating TF-target gene relationships, figuring out co-regulation patterns, and exploring the coordination of cell processes in response to changes in cell state or environment. Here we focus on queries aimed at validating regulatory network models, and on coordinating visualization of primary data and directed weighted gene regulatory networks. The large size of both the network models and the primary data can make such coordinated queries cumbersome with existing tools and, in particular, inhibits the sharing of results between collaborators. In this work, we develop and demonstrate a web-based framework for coordinating visualization and exploration of expression data (RNA-seq, microarray), network models and gene-binding data (ChIP-seq). Using specialized data structures and multiple coordinated views, we design an efficient querying model to support interactive analysis of the data. Finally, we show the effectiveness of our framework through case studies for the mouse immune system (a dataset focused on a subset of key cellular functions) and a model bacteria (a small genome with high data-completeness). PMID- 26356905 TI - The Spinel Explorer--Interactive Visual Analysis of Spinel Group Minerals. AB - Geologists usually deal with rocks that are up to several thousand million years old. They try to reconstruct the tectonic settings where these rocks were formed and the history of events that affected them through the geological time. The spinel group minerals provide useful information regarding the geological environment in which the host rocks were formed. They constitute excellent indicators of geological environments (tectonic settings) and are of invaluable help in the search for mineral deposits of economic interest. The current workflow requires the scientists to work with different applications to analyze spine data. They do use specific diagrams, but these are usually not interactive. The current workflow hinders domain experts to fully exploit the potentials of tediously and expensively collected data. In this paper, we introduce the Spinel Explorer-an interactive visual analysis application for spinel group minerals. The design of the Spinel Explorer and of the newly introduced interactions is a result of a careful study of geologists' tasks. The Spinel Explorer includes most of the diagrams commonly used for analyzing spinel group minerals, including 2D binary plots, ternary plots, and 3D Spinel prism plots. Besides specific plots, conventional information visualization views are also integrated in the Spinel Explorer. All views are interactive and linked. The Spinel Explorer supports conventional statistics commonly used in spinel minerals exploration. The statistics views and different data derivation techniques are fully integrated in the system. Besides the Spinel Explorer as newly proposed interactive exploration system, we also describe the identified analysis tasks, and propose a new workflow. We evaluate the Spinel Explorer using real-life data from two locations in Argentina: the Frontal Cordillera in Central Andes and Patagonia. We describe the new findings of the geologists which would have been much more difficult to achieve using the current workflow only. Very positive feedback from geologists confirms the usefulness of the Spinel Explorer. PMID- 26356906 TI - Visual Reconciliation of Alternative Similarity Spaces in Climate Modeling. AB - Visual data analysis often requires grouping of data objects based on their similarity. In many application domains researchers use algorithms and techniques like clustering and multidimensional scaling to extract groupings from data. While extracting these groups using a single similarity criteria is relatively straightforward, comparing alternative criteria poses additional challenges. In this paper we define visual reconciliation as the problem of reconciling multiple alternative similarity spaces through visualization and interaction. We derive this problem from our work on model comparison in climate science where climate modelers are faced with the challenge of making sense of alternative ways to describe their models: one through the output they generate, another through the large set of properties that describe them. Ideally, they want to understand whether groups of models with similar spatio-temporal behaviors share similar sets of criteria or, conversely, whether similar criteria lead to similar behaviors. We propose a visual analytics solution based on linked views, that addresses this problem by allowing the user to dynamically create, modify and observe the interaction among groupings, thereby making the potential explanations apparent. We present case studies that demonstrate the usefulness of our technique in the area of climate science. PMID- 26356907 TI - Learning Perceptual Kernels for Visualization Design. AB - Visualization design can benefit from careful consideration of perception, as different assignments of visual encoding variables such as color, shape and size affect how viewers interpret data. In this work, we introduce perceptual kernels: distance matrices derived from aggregate perceptual judgments. Perceptual kernels represent perceptual differences between and within visual variables in a reusable form that is directly applicable to visualization evaluation and automated design. We report results from crowd-sourced experiments to estimate kernels for color, shape, size and combinations thereof. We analyze kernels estimated using five different judgment types--including Likert ratings among pairs, ordinal triplet comparisons, and manual spatial arrangement--and compare them to existing perceptual models. We derive recommendations for collecting perceptual similarities, and then demonstrate how the resulting kernels can be applied to automate visualization design decisions. PMID- 26356908 TI - Ranking Visualizations of Correlation Using Weber's Law. AB - Despite years of research yielding systems and guidelines to aid visualization design, practitioners still face the challenge of identifying the best visualization for a given dataset and task. One promising approach to circumvent this problem is to leverage perceptual laws to quantitatively evaluate the effectiveness of a visualization design. Following previously established methodologies, we conduct a large scale (n=1687) crowdsourced experiment to investigate whether the perception of correlation in nine commonly used visualizations can be modeled using Weber's law. The results of this experiment contribute to our understanding of information visualization by establishing that: (1) for all tested visualizations, the precision of correlation judgment could be modeled by Weber's law, (2) correlation judgment precision showed striking variation between negatively and positively correlated data, and (3) Weber models provide a concise means to quantify, compare, and rank the perceptual precision afforded by a visualization. PMID- 26356909 TI - The relation between visualization size, grouping, and user performance. AB - In this paper we make the following contributions: (1) we describe how the grouping, quantity, and size of visual marks affects search time based on the results from two experiments; (2) we report how search performance relates to self-reported difficulty in finding the target for different display types; and (3) we present design guidelines based on our findings to facilitate the design of effective visualizations. Both Experiment 1 and 2 asked participants to search for a unique target in colored visualizations to test how the grouping, quantity, and size of marks affects user performance. In Experiment 1, the target square was embedded in a grid of squares and in Experiment 2 the target was a point in a scatterplot. Search performance was faster when colors were spatially grouped than when they were randomly arranged. The quantity of marks had little effect on search time for grouped displays ("pop-out"), but increasing the quantity of marks slowed reaction time for random displays. Regardless of color layout (grouped vs. random), response times were slowest for the smallest mark size and decreased as mark size increased to a point, after which response times plateaued. In addition to these two experiments we also include potential application areas, as well as results from a small case study where we report preliminary findings that size may affect how users infer how visualizations should be used. We conclude with a list of design guidelines that focus on how to best create visualizations based on grouping, quantity, and size of visual marks. PMID- 26356910 TI - A Principled Way of Assessing Visualization Literacy. AB - We describe a method for assessing the visualization literacy (VL) of a user. Assessing how well people understand visualizations has great value for research (e. g., to avoid confounds), for design (e. g., to best determine the capabilities of an audience), for teaching (e. g., to assess the level of new students), and for recruiting (e. g., to assess the level of interviewees). This paper proposes a method for assessing VL based on Item Response Theory. It describes the design and evaluation of two VL tests for line graphs, and presents the extension of the method to bar charts and scatterplots. Finally, it discusses the reimplementation of these tests for fast, effective, and scalable web-based use. PMID- 26356911 TI - Reinforcing Visual Grouping Cues to Communicate Complex Informational Structure. AB - In his book Multimedia Learning [7], Richard Mayer asserts that viewers learn best from imagery that provides them with cues to help them organize new information into the correct knowledge structures. Designers have long been exploiting the Gestalt laws of visual grouping to deliver viewers those cues using visual hierarchy, often communicating structures much more complex than the simple organizations studied in psychological research. Unfortunately, designers are largely practical in their work, and have not paused to build a complex theory of structural communication. If we are to build a tool to help novices create effective and well structured visuals, we need a better understanding of how to create them. Our work takes a first step toward addressing this lack, studying how five of the many grouping cues (proximity, color similarity, common region, connectivity, and alignment) can be effectively combined to communicate structured text and imagery from real world examples. To measure the effectiveness of this structural communication, we applied a digital version of card sorting, a method widely used in anthropology and cognitive science to extract cognitive structures. We then used tree edit distance to measure the difference between perceived and communicated structures. Our most significant findings are: 1) with careful design, complex structure can be communicated clearly; 2) communicating complex structure is best done with multiple reinforcing grouping cues; 3) common region (use of containers such as boxes) is particularly effective at communicating structure; and 4) alignment is a weak structural communicator. PMID- 26356912 TI - UpSet: Visualization of Intersecting Sets. AB - Understanding relationships between sets is an important analysis task that has received widespread attention in the visualization community. The major challenge in this context is the combinatorial explosion of the number of set intersections if the number of sets exceeds a trivial threshold. In this paper we introduce UpSet, a novel visualization technique for the quantitative analysis of sets, their intersections, and aggregates of intersections. UpSet is focused on creating task-driven aggregates, communicating the size and properties of aggregates and intersections, and a duality between the visualization of the elements in a dataset and their set membership. UpSet visualizes set intersections in a matrix layout and introduces aggregates based on groupings and queries. The matrix layout enables the effective representation of associated data, such as the number of elements in the aggregates and intersections, as well as additional summary statistics derived from subset or element attributes. Sorting according to various measures enables a task-driven analysis of relevant intersections and aggregates. The elements represented in the sets and their associated attributes are visualized in a separate view. Queries based on containment in specific intersections, aggregates or driven by attribute filters are propagated between both views. We also introduce several advanced visual encodings and interaction methods to overcome the problems of varying scales and to address scalability. UpSet is web-based and open source. We demonstrate its general utility in multiple use cases from various domains. PMID- 26356914 TI - DimpVis: Exploring Time-varying Information Visualizations by Direct Manipulation. AB - We introduce a new direct manipulation technique, DimpVis, for interacting with visual items in information visualizations to enable exploration of the time dimension. DimpVis is guided by visual hint paths which indicate how a selected data item changes through the time dimension in a visualization. Temporal navigation is controlled by manipulating any data item along its hint path. All other items are updated to reflect the new time. We demonstrate how the DimpVis technique can be designed to directly manipulate position, colour, and size in familiar visualizations such as bar charts and scatter plots, as a means for temporal navigation. We present results from a comparative evaluation, showing that the DimpVis technique was subjectively preferred and quantitatively competitive with the traditional time slider, and significantly faster than small multiples for a variety of tasks. PMID- 26356913 TI - OnSet: A Visualization Technique for Large-scale Binary Set Data. AB - Visualizing sets to reveal relationships between constituent elements is a complex representational problem. Recent research presents several automated placement and grouping techniques to highlight connections between set elements. However, these techniques do not scale well for sets with cardinality greater than one hundred elements. We present OnSet, an interactive, scalable visualization technique for representing large-scale binary set data. The visualization technique defines a single, combined domain of elements for all sets, and models each set by the elements that it both contains and does not contain. OnSet employs direct manipulation interaction and visual highlighting to support easy identification of commonalities and differences as well as membership patterns across different sets of elements. We present case studies to illustrate how the technique can be successfully applied across different domains such as bio-chemical metabolomics and task and event scheduling. PMID- 26356915 TI - Axis Calibration for Improving Data Attribute Estimation in Star Coordinates Plots. AB - Star coordinates is a well-known multivariate visualization method that produces linear dimensionality reduction mappings through a set of radial axes defined by vectors in an observable space. One of its main drawbacks concerns the difficulty to recover attributes of data samples accurately, which typically lie in the [0], [1] interval, given the locations of the low-dimensional embeddings and the vectors. In this paper we show that centering the data can considerably increase attribute estimation accuracy, where data values can be read off approximately by projecting embedded points onto calibrated (i.e., labeled) axes, similarly to classical statistical biplots. In addition, this idea can be coupled with a recently developed orthonormalization process on the axis vectors that prevents unnecessary distortions. We demonstrate that the combination of both approaches not only enhances the estimates, but also provides more faithful representations of the data. PMID- 26356916 TI - Domino: Extracting, Comparing, and Manipulating Subsets Across Multiple Tabular Datasets. AB - Answering questions about complex issues often requires analysts to take into account information contained in multiple interconnected datasets. A common strategy in analyzing and visualizing large and heterogeneous data is dividing it into meaningful subsets. Interesting subsets can then be selected and the associated data and the relationships between the subsets visualized. However, neither the extraction and manipulation nor the comparison of subsets is well supported by state-of-the-art techniques. In this paper we present Domino, a novel multiform visualization technique for effectively representing subsets and the relationships between them. By providing comprehensive tools to arrange, combine, and extract subsets, Domino allows users to create both common visualization techniques and advanced visualizations tailored to specific use cases. In addition to the novel technique, we present an implementation that enables analysts to manage the wide range of options that our approach offers. Innovative interactive features such as placeholders and live previews support rapid creation of complex analysis setups. We introduce the technique and the implementation using a simple example and demonstrate scalability and effectiveness in a use case from the field of cancer genomics. PMID- 26356917 TI - Attribute Signatures: Dynamic Visual Summaries for Analyzing Multivariate Geographical Data. AB - The visual analysis of geographically referenced datasets with a large number of attributes is challenging due to the fact that the characteristics of the attributes are highly dependent upon the locations at which they are focussed, and the scale and time at which they are measured. Specialized interactive visual methods are required to help analysts in understanding the characteristics of the attributes when these multiple aspects are considered concurrently. Here, we develop attribute signatures-interactively crafted graphics that show the geographic variability of statistics of attributes through which the extent of dependency between the attributes and geography can be visually explored. We compute a number of statistical measures, which can also account for variations in time and scale, and use them as a basis for our visualizations. We then employ different graphical configurations to show and compare both continuous and discrete variation of location and scale. Our methods allow variation in multiple statistical summaries of multiple attributes to be considered concurrently and geographically, as evidenced by examples in which the census geography of London and the wider UK are explored. PMID- 26356918 TI - Origin-Destination Flow Data Smoothing and Mapping. AB - This paper presents a new approach to flow mapping that extracts inherent patterns from massive geographic mobility data and constructs effective visual representations of the data for the understanding of complex flow trends. This approach involves a new method for origin-destination flow density estimation and a new method for flow map generalization, which together can remove spurious data variance, normalize flows with control population, and detect high-level patterns that are not discernable with existing approaches. The approach achieves three main objectives in addressing the challenges for analyzing and mapping massive flow data. First, it removes the effect of size differences among spatial units via kernel-based density estimation, which produces a measurement of flow volume between each pair of origin and destination. Second, it extracts major flow patterns in massive flow data through a new flow sampling method, which filters out duplicate information in the smoothed flows. Third, it enables effective flow mapping and allows intuitive perception of flow patterns among origins and destinations without bundling or altering flow paths. The approach can work with both point-based flow data (such as taxi trips with GPS locations) and area-based flow data (such as county-to-county migration). Moreover, the approach can be used to detect and compare flow patterns at different scales or in relatively sparse flow datasets, such as migration for each age group. We evaluate and demonstrate the new approach with case studies of U.S. migration data and experiments with synthetic data. PMID- 26356919 TI - Stenomaps: Shorthand for shapes. AB - We address some of the challenges in representing spatial data with a novel form of geometric abstraction-the stenomap. The stenomap comprises a series of smoothly curving linear glyphs that each represent both the boundary and the area of a polygon. We present an efficient algorithm to automatically generate these open, C1-continuous splines from a set of input polygons. Feature points of the input polygons are detected using the medial axis to maintain important shape properties. We use dynamic programming to compute a planar non-intersecting spline representing each polygon's base shape. The results are stylised glyphs whose appearance may be parameterised and that offer new possibilities in the 'cartographic design space'. We compare our glyphs with existing forms of geometric schematisation and discuss their relative merits and shortcomings. We describe several use cases including the depiction of uncertain model data in the form of hurricane track forecasting; minimal ink thematic mapping; and the depiction of continuous statistical data. PMID- 26356920 TI - Nmap: A Novel Neighborhood Preservation Space-filling Algorithm. AB - Space-filling techniques seek to use as much as possible the visual space to represent a dataset, splitting it into regions that represent the data elements. Amongst those techniques, Treemaps have received wide attention due to its simplicity, reduced visual complexity, and compact use of the available space. Several different Treemap algorithms have been proposed, however the core idea is the same, to divide the visual space into rectangles with areas proportional to some data attribute or weight. Although pleasant layouts can be effectively produced by the existing techniques, most of them do not take into account relationships that might exist between different data elements when partitioning the visual space. This violates the distance-similarity metaphor, that is, close rectangles do not necessarily represent similar data elements. In this paper, we propose a novel approach, called Neighborhood Treemap (Nmap), that seeks to solve this limitation by employing a slice and scale strategy where the visual space is successively bisected on the horizontal or vertical directions and the bisections are scaled until one rectangle is defined per data element. Compared to the current techniques with the same similarity preservation goal, our approach presents the best results while being two to three orders of magnitude faster. The usefulness of Nmap is shown by two applications involving the organization of document collections and the construction of cartograms illustrating its effectiveness on different scenarios. PMID- 26356921 TI - Tree Colors: Color Schemes for Tree-Structured Data. AB - We present a method to map tree structures to colors from the Hue-Chroma Luminance color model, which is known for its well balanced perceptual properties. The Tree Colors method can be tuned with several parameters, whose effect on the resulting color schemes is discussed in detail. We provide a free and open source implementation with sensible parameter defaults. Categorical data are very common in statistical graphics, and often these categories form a classification tree. We evaluate applying Tree Colors to tree structured data with a survey on a large group of users from a national statistical institute. Our user study suggests that Tree Colors are useful, not only for improving node link diagrams, but also for unveiling tree structure in non-hierarchical visualizations. PMID- 26356922 TI - Revisiting Bertin Matrices: New Interactions for Crafting Tabular Visualizations. AB - We present Bertifier, a web app for rapidly creating tabular visualizations from spreadsheets. Bertifier draws from Jacques Bertin's matrix analysis method, whose goal was to "simplify without destroying" by encoding cell values visually and grouping similar rows and columns. Although there were several attempts to bring this method to computers, no implementation exists today that is both exhaustive and accessible to a large audience. Bertifier remains faithful to Bertin's method while leveraging the power of today's interactive computers. Tables are formatted and manipulated through crossets, a new interaction technique for rapidly applying operations on rows and columns. We also introduce visual reordering, a semi-interactive reordering approach that lets users apply and tune automatic reordering algorithms in a WYSIWYG manner. Sessions with eight users from different backgrounds suggest that Bertifier has the potential to bring Bertin's method to a wider audience of both technical and non-technical users, and empower them with data analysis and communication tools that were so far only accessible to a handful of specialists. PMID- 26356923 TI - iVisDesigner: Expressive Interactive Design of Information Visualizations. AB - We present the design, implementation and evaluation of iVisDesigner, a web-based system that enables users to design information visualizations for complex datasets interactively, without the need for textual programming. Our system achieves high interactive expressiveness through conceptual modularity, covering a broad information visualization design space. iVisDesigner supports the interactive design of interactive visualizations, such as provisioning for responsive graph layouts and different types of brushing and linking interactions. We present the system design and implementation, exemplify it through a variety of illustrative visualization designs and discuss its limitations. A performance analysis and an informal user study are presented to evaluate the system. PMID- 26356924 TI - Constructing Visual Representations: Investigating the Use of Tangible Tokens. AB - The accessibility of infovis authoring tools to a wide audience has been identified as a major research challenge. A key task in the authoring process is the development of visual mappings. While the infovis community has long been deeply interested in finding effective visual mappings, comparatively little attention has been placed on how people construct visual mappings. In this paper, we present the results of a study designed to shed light on how people transform data into visual representations. We asked people to create, update and explain their own information visualizations using only tangible building blocks. We learned that all participants, most of whom had little experience in visualization authoring, were readily able to create and talk about their own visualizations. Based on our observations, we discuss participants' actions during the development of their visual representations and during their analytic activities. We conclude by suggesting implications for tool design to enable broader support for infovis authoring. PMID- 26356925 TI - PanoramicData: Data Analysis through Pen & Touch. AB - Interactively exploring multidimensional datasets requires frequent switching among a range of distinct but inter-related tasks (e.g., producing different visuals based on different column sets, calculating new variables, and observing the interactions between sets of data). Existing approaches either target specific different problem domains (e.g., data-transformation or data presentation) or expose only limited aspects of the general exploratory process; in either case, users are forced to adopt coping strategies (e.g., arranging windows or using undo as a mechanism for comparison instead of using side-by-side displays) to compensate for the lack of an integrated suite of exploratory tools. PanoramicData (PD) addresses these problems by unifying a comprehensive set of tools for visual data exploration into a hybrid pen and touch system designed to exploit the visualization advantages of large interactive displays. PD goes beyond just familiar visualizations by including direct UI support for data transformation and aggregation, filtering and brushing. Leveraging an unbounded whiteboard metaphor, users can combine these tools like building blocks to create detailed interactive visual display networks in which each visualization can act as a filter for others. Further, by operating directly on relational-databases, PD provides an approachable visual language that exposes a broad set of the expressive power of SQL including functionally complete logic filtering, computation of aggregates and natural table joins. To understand the implications of this novel approach, we conducted a formative user study with both data and visualization experts. The results indicated that the system provided a fluid and natural user experience for probing multi-dimensional data and was able to cover the full range of queries that the users wanted to pose. PMID- 26356926 TI - The Effects of Interactive Latency on Exploratory Visual Analysis. AB - To support effective exploration, it is often stated that interactive visualizations should provide rapid response times. However, the effects of interactive latency on the process and outcomes of exploratory visual analysis have not been systematically studied. We present an experiment measuring user behavior and knowledge discovery with interactive visualizations under varying latency conditions. We observe that an additional delay of 500 ms incurs significant costs, decreasing user activity and data set coverage. Analyzing verbal data from think-aloud protocols, we find that increased latency reduces the rate at which users make observations, draw generalizations and generate hypotheses. Moreover, we note interaction effects in which initial exposure to higher latencies leads to subsequently reduced performance in a low-latency setting. Overall, increased latency causes users to shift exploration strategy, in turn affecting performance. We discuss how these results can inform the design of interactive analysis tools. PMID- 26356927 TI - Visualizing Statistical Mix Effects and Simpson's Paradox. AB - We discuss how "mix effects" can surprise users of visualizations and potentially lead them to incorrect conclusions. This statistical issue (also known as "omitted variable bias" or, in extreme cases, as "Simpson's paradox") is widespread and can affect any visualization in which the quantity of interest is an aggregated value such as a weighted sum or average. Our first contribution is to document how mix effects can be a serious issue for visualizations, and we analyze how mix effects can cause problems in a variety of popular visualization techniques, from bar charts to treemaps. Our second contribution is a new technique, the "comet chart," that is meant to ameliorate some of these issues. PMID- 26356928 TI - Error Bars Considered Harmful: Exploring Alternate Encodings for Mean and Error. AB - When making an inference or comparison with uncertain, noisy, or incomplete data, measurement error and confidence intervals can be as important for judgment as the actual mean values of different groups. These often misunderstood statistical quantities are frequently represented by bar charts with error bars. This paper investigates drawbacks with this standard encoding, and considers a set of alternatives designed to more effectively communicate the implications of mean and error data to a general audience, drawing from lessons learned from the use of visual statistics in the information visualization community. We present a series of crowd-sourced experiments that confirm that the encoding of mean and error significantly changes how viewers make decisions about uncertain data. Careful consideration of design tradeoffs in the visual presentation of data results in human reasoning that is more consistently aligned with statistical inferences. We suggest the use of gradient plots (which use transparency to encode uncertainty) and violin plots (which use width) as better alternatives for inferential tasks than bar charts with error bars. PMID- 26356929 TI - Four Experiments on the Perception of Bar Charts. AB - Bar charts are one of the most common visualization types. In a classic graphical perception paper, Cleveland & McGill studied how different bar chart designs impact the accuracy with which viewers can complete simple perceptual tasks. They found that people perform substantially worse on stacked bar charts than on aligned bar charts, and that comparisons between adjacent bars are more accurate than between widely separated bars. However, the study did not explore why these differences occur. In this paper, we describe a series of follow-up experiments to further explore and explain their results. While our results generally confirm Cleveland & McGill's ranking of various bar chart configurations, we provide additional insight into the bar chart reading task and the sources of participants' errors. We use our results to propose new hypotheses on the perception of bar charts. PMID- 26356930 TI - Visual Parameter Space Analysis: A Conceptual Framework. AB - Various case studies in different application domains have shown the great potential of visual parameter space analysis to support validating and using simulation models. In order to guide and systematize research endeavors in this area, we provide a conceptual framework for visual parameter space analysis problems. The framework is based on our own experience and a structured analysis of the visualization literature. It contains three major components: (1) a data flow model that helps to abstractly describe visual parameter space analysis problems independent of their application domain; (2) a set of four navigation strategies of how parameter space analysis can be supported by visualization tools; and (3) a characterization of six analysis tasks. Based on our framework, we analyze and classify the current body of literature, and identify three open research gaps in visual parameter space analysis. The framework and its discussion are meant to support visualization designers and researchers in characterizing parameter space analysis problems and to guide their design and evaluation processes. PMID- 26356931 TI - Moving beyond sequential design: Reflections on a rich multi-channel approach to data visualization. AB - We reflect on a four-year engagement with transport authorities and others involving a large dataset describing the use of a public bicycle-sharing scheme. We describe the role visualization of these data played in fostering engagement with policy makers, transport operators, the transport research community, the museum and gallery sector and the general public. We identify each of these as 'channels'--evolving relationships between producers and consumers of visualization--where traditional roles of the visualization expert and domain expert are blurred. In each case, we identify the different design decisions that were required to support each of these channels and the role played by the visualization process. Using chauffeured interaction with a flexible visual analytics system we demonstrate how insight was gained by policy makers into gendered spatio-temporal cycle behaviors, how this led to further insight into workplace commuting activity, group cycling behavior and explanations for street navigation choice. We demonstrate how this supported, and was supported by, the seemingly unrelated development of narrative-driven visualization via TEDx, of the creation and the setting of an art installation and the curating of digital and physical artefacts. We assert that existing models of visualization design, of tool/technique development and of insight generation do not adequately capture the richness of parallel engagement via these multiple channels of communication. We argue that developing multiple channels in parallel opens up opportunities for visualization design and analysis by building trust and authority and supporting creativity. This rich, non-sequential approach to visualization design is likely to foster serendipity, deepen insight and increase impact. PMID- 26356932 TI - An Algebraic Process for Visualization Design. AB - We present a model of visualization design based on algebraic considerations of the visualization process. The model helps characterize visual encodings, guide their design, evaluate their effectiveness, and highlight their shortcomings. The model has three components: the underlying mathematical structure of the data or object being visualized, the concrete representation of the data in a computer, and (to the extent possible) a mathematical description of how humans perceive the visualization. Because we believe the value of our model lies in its practical application, we propose three general principles for good visualization design. We work through a collection of examples where our model helps explain the known properties of existing visualizations methods, both good and not-so good, as well as suggesting some novel methods. We describe how to use the model alongside experimental user studies, since it can help frame experiment outcomes in an actionable manner. Exploring the implications and applications of our model and its design principles should provide many directions for future visualization research. PMID- 26356933 TI - Design Activity Framework for Visualization Design. AB - An important aspect in visualization design is the connection between what a designer does and the decisions the designer makes. Existing design process models, however, do not explicitly link back to models for visualization design decisions. We bridge this gap by introducing the design activity framework, a process model that explicitly connects to the nested model, a well-known visualization design decision model. The framework includes four overlapping activities that characterize the design process, with each activity explicating outcomes related to the nested model. Additionally, we describe and characterize a list of exemplar methods and how they overlap among these activities. The design activity framework is the result of reflective discussions from a collaboration on a visualization redesign project, the details of which we describe to ground the framework in a real-world design process. Lastly, from this redesign project we provide several research outcomes in the domain of cybersecurity, including an extended data abstraction and rich opportunities for future visualization research. PMID- 26356934 TI - Activity Sculptures: Exploring the Impact of Physical Visualizations on Running Activity. AB - Data sculptures are a promising type of visualizations in which data is given a physical form. In the past, they have mostly been used for artistic, communicative or educational purposes, and designers of data sculptures argue that in such situations, physical visualizations can be more enriching than pixel based visualizations. We present the design of Activity Sculptures: data sculptures of running activity. In a three-week field study we investigated the impact of the sculptures on 14 participants' running activity, the personal and social behaviors generated by the sculptures, as well as participants' experiences when receiving these individual physical tokens generated from the specific data of their runs. The physical rewards generated curiosity and personal experimentation but also social dynamics such as discussion on runs or envy/competition. We argue that such passive (or calm) visualizations can complement nudging and other mechanisms of persuasion with a more playful and reflective look at ones' activity. PMID- 26356935 TI - The Persuasive Power of Data Visualization. AB - Data visualization has been used extensively to inform users. However, little research has been done to examine the effects of data visualization in influencing users or in making a message more persuasive. In this study, we present experimental research to fill this gap and present an evidence-based analysis of persuasive visualization. We built on persuasion research from psychology and user interfaces literature in order to explore the persuasive effects of visualization. In this experimental study we define the circumstances under which data visualization can make a message more persuasive, propose hypotheses, and perform quantitative and qualitative analyses on studies conducted to test these hypotheses. We compare visual treatments with data presented through barcharts and linecharts on the one hand, treatments with data presented through tables on the other, and then evaluate their persuasiveness. The findings represent a first step in exploring the effectiveness of persuasive visualization. PMID- 26356936 TI - Comparative Eye Tracking Study on Node-Link Visualizations of Trajectories. AB - We present the results of an eye tracking study that compares different visualization methods for long, dense, complex, and piecewise linear spatial trajectories. Typical sources of such data are from temporally discrete measurements of the positions of moving objects, for example, recorded GPS tracks of animals in movement ecology. In the repeated-measures within-subjects user study, four variants of node-link visualization techniques are compared, with the following representations of directed links: standard arrow, tapered, equidistant arrows, and equidistant comets. In addition, we investigate the effect of rendering order for the halo visualization of those links as well as the usefulness of node splatting. All combinations of link visualization techniques are tested for different trajectory density levels. We used three types of tasks: tracing of paths, identification of longest links, and estimation of the density of trajectory clusters. Results are presented in the form of the statistical evaluation of task completion time, task solution accuracy, and two eye tracking metrics. These objective results are complemented by a summary of subjective feedback from the participants. The main result of our study is that tapered links perform very well. However, we discuss that equidistant comets and equidistant arrows are a good option to perceive direction information independent of zoom-level of the display. PMID- 26356937 TI - Node, Node-Link, and Node-Link-Group Diagrams: An Evaluation. AB - Effectively showing the relationships between objects in a dataset is one of the main tasks in information visualization. Typically there is a well-defined notion of distance between pairs of objects, and traditional approaches such as principal component analysis or multi-dimensional scaling are used to place the objects as points in 2D space, so that similar objects are close to each other. In another typical setting, the dataset is visualized as a network graph, where related nodes are connected by links. More recently, datasets are also visualized as maps, where in addition to nodes and links, there is an explicit representation of groups and clusters. We consider these three Techniques, characterized by a progressive increase of the amount of encoded information: node diagrams, node-link diagrams and node-link-group diagrams. We assess these three types of diagrams with a controlled experiment that covers nine different tasks falling broadly in three categories: node-based tasks, network-based tasks and group-based tasks. Our findings indicate that adding links, or links and group representations, does not negatively impact performance (time and accuracy) of node-based tasks. Similarly, adding group representations does not negatively impact the performance of network-based tasks. Node-link-group diagrams outperform the others on group-based tasks. These conclusions contradict results in other studies, in similar but subtly different settings. Taken together, however, such results can have significant implications for the design of standard and domain snecific visualizations tools. PMID- 26356938 TI - The Not-so-Staggering Effect of Staggered Animated Transitions on Visual Tracking. AB - Interactive visual applications often rely on animation to transition from one display state to another. There are multiple animation techniques to choose from, and it is not always clear which should produce the best visual correspondences between display elements. One major factor is whether the animation relies on staggering-an incremental delay in start times across the moving elements. It has been suggested that staggering may reduce occlusion, while also reducing display complexity and producing less overwhelming animations, though no empirical evidence has demonstrated these advantages. Work in perceptual psychology does show that reducing occlusion, and reducing inter-object proximity (crowding) more generally, improves performance in multiple object tracking. We ran simulations confirming that staggering can in some cases reduce crowding in animated transitions involving dot clouds (as found in, e.g., animated 2D scatterplots). We empirically evaluated the effect of two staggering techniques on tracking tasks, focusing on cases that should most favour staggering. We found that introducing staggering has a negligible, or even negative, impact on multiple object tracking performance. The potential benefits of staggering may be outweighed by strong costs: a loss of common-motion grouping information about which objects travel in similar paths, and less predictability about when any specific object would begin to move. Staggering may be beneficial in some conditions, but they have yet to be demonstrated. The present results are a significant step toward a better understanding of animation pacing, and provide direction for further research. PMID- 26356939 TI - The Influence of Contour on Similarity Perception of Star Glyphs. AB - We conducted three experiments to investigate the effects of contours on the detection of data similarity with star glyph variations. A star glyph is a small, compact, data graphic that represents a multi-dimensional data point. Star glyphs are often used in small-multiple settings, to represent data points in tables, on maps, or as overlays on other types of data graphics. In these settings, an important task is the visual comparison of the data points encoded in the star glyph, for example to find other similar data points or outliers. We hypothesized that for data comparisons, the overall shape of a star glyph--enhanced through contour lines--would aid the viewer in making accurate similarity judgments. To test this hypothesis, we conducted three experiments. In our first experiment, we explored how the use of contours influenced how visualization experts and trained novices chose glyphs with similar data values. Our results showed that glyphs without contours make the detection of data similarity easier. Given these results, we conducted a second study to understand intuitive notions of similarity. Star glyphs without contours most intuitively supported the detection of data similarity. In a third experiment, we tested the effect of star glyph reference structures (i.e., tickmarks and gridlines) on the detection of similarity. Surprisingly, our results show that adding reference structures does improve the correctness of similarity judgments for star glyphs with contours, but not for the standard star glyph. As a result of these experiments, we conclude that the simple star glyph without contours performs best under several criteria, reinforcing its practice and popularity in the literature. Contours seem to enhance the detection of other types of similarity, e. g., shape similarity and are distracting when data similarity has to be judged. Based on these findings we provide design considerations regarding the use of contours and reference structures on star glyphs. PMID- 26356940 TI - Order of Magnitude Markers: An Empirical Study on Large Magnitude Number Detection. AB - In this paper we introduce Order of Magnitude Markers (OOMMs) as a new technique for number representation. The motivation for this work is that many data sets require the depiction and comparison of numbers that have varying orders of magnitude. Existing techniques for representation use bar charts, plots and colour on linear or logarithmic scales. These all suffer from related problems. There is a limit to the dynamic range available for plotting numbers, and so the required dynamic range of the plot can exceed that of the depiction method. When that occurs, resolving, comparing and relating values across the display becomes problematical or even impossible for the user. With this in mind, we present an empirical study in which we compare logarithmic, linear, scale-stack bars and our new markers for 11 different stimuli grouped into 4 different tasks across all 8 marker types. PMID- 26356941 TI - Overview: The Design, Adoption, and Analysis of a Visual Document Mining Tool for Investigative Journalists. AB - For an investigative journalist, a large collection of documents obtained from a Freedom of Information Act request or a leak is both a blessing and a curse: such material may contain multiple newsworthy stories, but it can be difficult and time consuming to find relevant documents. Standard text search is useful, but even if the search target is known it may not be possible to formulate an effective query. In addition, summarization is an important non-search task. We present Overview, an application for the systematic analysis of large document collections based on document clustering, visualization, and tagging. This work contributes to the small set of design studies which evaluate a visualization system "in the wild", and we report on six case studies where Overview was voluntarily used by self-initiated journalists to produce published stories. We find that the frequently-used language of "exploring" a document collection is both too vague and too narrow to capture how journalists actually used our application. Our iterative process, including multiple rounds of deployment and observations of real world usage, led to a much more specific characterization of tasks. We analyze and justify the visual encoding and interaction techniques used in Overview's design with respect to our final task abstractions, and propose generalizable lessons for visualization design methodology. PMID- 26356942 TI - How Hierarchical Topics Evolve in Large Text Corpora. AB - Using a sequence of topic trees to organize documents is a popular way to represent hierarchical and evolving topics in text corpora. However, following evolving topics in the context of topic trees remains difficult for users. To address this issue, we present an interactive visual text analysis approach to allow users to progressively explore and analyze the complex evolutionary patterns of hierarchical topics. The key idea behind our approach is to exploit a tree cut to approximate each tree and allow users to interactively modify the tree cuts based on their interests. In particular, we propose an incremental evolutionary tree cut algorithm with the goal of balancing 1) the fitness of each tree cut and the smoothness between adjacent tree cuts; 2) the historical and new information related to user interests. A time-based visualization is designed to illustrate the evolving topics over time. To preserve the mental map, we develop a stable layout algorithm. As a result, our approach can quickly guide users to progressively gain profound insights into evolving hierarchical topics. We evaluate the effectiveness of the proposed method on Amazon's Mechanical Turk and real-world news data. The results show that users are able to successfully analyze evolving topics in text data. PMID- 26356943 TI - Exploring the Placement and Design of Word-Scale Visualizations. AB - We present an exploration and a design space that characterize the usage and placement of word-scale visualizations within text documents. Word-scale visualizations are a more general version of sparklines--small, word-sized data graphics that allow meta-information to be visually presented in-line with document text. In accordance with Edward Tufte's definition, sparklines are traditionally placed directly before or after words in the text. We describe alternative placements that permit a wider range of word-scale graphics and more flexible integration with text layouts. These alternative placements include positioning visualizations between lines, within additional vertical and horizontal space in the document, and as interactive overlays on top of the text. Each strategy changes the dimensions of the space available to display the visualizations, as well as the degree to which the text must be adjusted or reflowed to accommodate them. We provide an illustrated design space of placement options for word-scale visualizations and identify six important variables that control the placement of the graphics and the level of disruption of the source text. We also contribute a quantitative analysis that highlights the effect of different placements on readability and text disruption. Finally, we use this analysis to propose guidelines to support the design and placement of word-scale visualizations. PMID- 26356944 TI - Effects of Presentation Mode and Pace Control on Performance in Image Classification. AB - A common task in visualization is to quickly find interesting items in large sets. When appropriate metadata is missing, automatic queries are impossible and users have to inspect all elements visually. We compared two fundamentally different, but obvious display modes for this task and investigated the difference with respect to effectiveness, efficiency, and satisfaction. The static mode is based on the page metaphor and presents successive pages with a static grid of items. The moving mode is based on the conveyor belt metaphor and lets a grid of items slide though the screen in a continuous flow. In our evaluation, we applied both modes to the common task of browsing images. We performed two experiments where 18 participants had to search for certain target images in a large image collection. The number of shown images per second (pace) was predefined in the first experiment, and under user control in the second one. We conclude that at a fixed pace, the mode has no significant impact on the recall. The perceived pace is generally slower for moving mode, which causes users to systematically choose for a faster real pace than in static mode at the cost of recall, keeping the average number of target images found per second equal for both modes. PMID- 26356945 TI - Multivariate Network Exploration and Presentation: From Detail to Overview via Selections and Aggregations. AB - Network data is ubiquitous; e-mail traffic between persons, telecommunication, transport and financial networks are some examples. Often these networks are large and multivariate, besides the topological structure of the network, multivariate data on the nodes and links is available. Currently, exploration and analysis methods are focused on a single aspect; the network topology or the multivariate data. In addition, tools and techniques are highly domain specific and require expert knowledge. We focus on the non-expert user and propose a novel solution for multivariate network exploration and analysis that tightly couples structural and multivariate analysis. In short, we go from Detail to Overview via Selections and Aggregations (DOSA): users are enabled to gain insights through the creation of selections of interest (manually or automatically), and producing high-level, infographic-style overviews simultaneously. Finally, we present example explorations on real-world datasets that demonstrate the effectiveness of our method for the exploration and understanding of multivariate networks where presentation of findings comes for free. PMID- 26356946 TI - GLO-STIX: Graph-Level Operations for Specifying Techniques and Interactive eXploration. AB - The field of graph visualization has produced a wealth of visualization techniques for accomplishing a variety of analysis tasks. Therefore analysts often rely on a suite of different techniques, and visual graph analysis application builders strive to provide this breadth of techniques. To provide a holistic model for specifying network visualization techniques (as opposed to considering each technique in isolation) we present the Graph-Level Operations (GLO) model. We describe a method for identifying GLOs and apply it to identify five classes of GLOs, which can be flexibly combined to re-create six canonical graph visualization techniques. We discuss advantages of the GLO model, including potentially discovering new, effective network visualization techniques and easing the engineering challenges of building multi-technique graph visualization applications. Finally, we implement the GLOs that we identified into the GLO-STIX prototype system that enables an analyst to interactively explore a graph by applying GLOs. PMID- 26356947 TI - LiveGantt: Interactively Visualizing a Large Manufacturing Schedule. AB - In this paper, we introduce LiveGantt as a novel interactive schedule visualization tool that helps users explore highly-concurrent large schedules from various perspectives. Although a Gantt chart is the most common approach to illustrate schedules, currently available Gantt chart visualization tools suffer from limited scalability and lack of interactions. LiveGantt is built with newly designed algorithms and interactions to improve conventional charts with better scalability, explorability, and reschedulability. It employs resource reordering and task aggregation to display the schedules in a scalable way. LiveGantt provides four coordinated views and filtering techniques to help users explore and interact with the schedules in more flexible ways. In addition, LiveGantt is equipped with an efficient rescheduler to allow users to instantaneously modify their schedules based on their scheduling experience in the fields. To assess the usefulness of the application of LiveGantt, we conducted a case study on manufacturing schedule data with four industrial engineering researchers. Participants not only grasped an overview of a schedule but also explored the schedule from multiple perspectives to make enhancements. PMID- 26356948 TI - TenniVis: Visualization for Tennis Match Analysis. AB - Existing research efforts into tennis visualization have primarily focused on using ball and player tracking data to enhance professional tennis broadcasts and to aid coaches in helping their students. Gathering and analyzing this data typically requires the use of an array of synchronized cameras, which are expensive for non-professional tennis matches. In this paper, we propose TenniVis, a novel tennis match visualization system that relies entirely on data that can be easily collected, such as score, point outcomes, point lengths, service information, and match videos that can be captured by one consumer-level camera. It provides two new visualizations to allow tennis coaches and players to quickly gain insights into match performance. It also provides rich interactions to support ad hoc hypothesis development and testing. We first demonstrate the usefulness of the system by analyzing the 2007 Australian Open men's singles final. We then validate its usability by two pilot user studies where two college tennis coaches analyzed the matches of their own players. The results indicate that useful insights can quickly be discovered and ad hoc hypotheses based on these insights can conveniently be tested through linked match videos. PMID- 26356949 TI - Combing the Communication Hairball: Visualizing Parallel Execution Traces using Logical Time. AB - With the continuous rise in complexity of modern supercomputers, optimizing the performance of large-scale parallel programs is becoming increasingly challenging. Simultaneously, the growth in scale magnifies the impact of even minor inefficiencies--potentially millions of compute hours and megawatts in power consumption can be wasted on avoidable mistakes or sub-optimal algorithms. This makes performance analysis and optimization critical elements in the software development process. One of the most common forms of performance analysis is to study execution traces, which record a history of per-process events and interprocess messages in a parallel application. Trace visualizations allow users to browse this event history and search for insights into the observed performance behavior. However, current visualizations are difficult to understand even for small process counts and do not scale gracefully beyond a few hundred processes. Organizing events in time leads to a virtually unintelligible conglomerate of interleaved events and moderately high process counts overtax even the largest display. As an alternative, we present a new trace visualization approach based on transforming the event history into logical time inferred directly from happened-before relationships. This emphasizes the code's structural behavior, which is much more familiar to the application developer. The original timing data, or other information, is then encoded through color, leading to a more intuitive visualization. Furthermore, we use the discrete nature of logical timelines to cluster processes according to their local behavior leading to a scalable visualization of even long traces on large process counts. We demonstrate our system using two case studies on large-scale parallel codes. PMID- 26356950 TI - MovExp: A Versatile Visualization Tool for Human-Computer Interaction Studies with 3D Performance and Biomechanical Data. AB - In Human-Computer Interaction (HCI), experts seek to evaluate and compare the performance and ergonomics of user interfaces. Recently, a novel cost-efficient method for estimating physical ergonomics and performance has been introduced to HCI. It is based on optical motion capture and biomechanical simulation. It provides a rich source for analyzing human movements summarized in a multidimensional data set. Existing visualization tools do not sufficiently support the HCI experts in analyzing this data. We identified two shortcomings. First, appropriate visual encodings are missing particularly for the biomechanical aspects of the data. Second, the physical setup of the user interface cannot be incorporated explicitly into existing tools. We present MovExp, a versatile visualization tool that supports the evaluation of user interfaces. In particular, it can be easily adapted by the HCI experts to include the physical setup that is being evaluated, and visualize the data on top of it. Furthermore, it provides a variety of visual encodings to communicate muscular loads, movement directions, and other specifics of HCI studies that employ motion capture and biomechanical simulation. In this design study, we follow a problem driven research approach. Based on a formalization of the visualization needs and the data structure, we formulate technical requirements for the visualization tool and present novel solutions to the analysis needs of the HCI experts. We show the utility of our tool with four case studies from the daily work of our HCI experts. PMID- 26356951 TI - NeuroLines: A Subway Map Metaphor for Visualizing Nanoscale Neuronal Connectivity. AB - We present NeuroLines, a novel visualization technique designed for scalable detailed analysis of neuronal connectivity at the nanoscale level. The topology of 3D brain tissue data is abstracted into a multi-scale, relative distance preserving subway map visualization that allows domain scientists to conduct an interactive analysis of neurons and their connectivity. Nanoscale connectomics aims at reverse-engineering the wiring of the brain. Reconstructing and analyzing the detailed connectivity of neurons and neurites (axons, dendrites) will be crucial for understanding the brain and its development and diseases. However, the enormous scale and complexity of nanoscale neuronal connectivity pose big challenges to existing visualization techniques in terms of scalability. NeuroLines offers a scalable visualization framework that can interactively render thousands of neurites, and that supports the detailed analysis of neuronal structures and their connectivity. We describe and analyze the design of NeuroLines based on two real-world use-cases of our collaborators in developmental neuroscience, and investigate its scalability to large-scale neuronal connectivity data. PMID- 26356952 TI - Predicate-Based Focus-and-Context Visualization for 3D Ultrasound. AB - Direct volume visualization techniques offer powerful insight into volumetric medical images and are part of the clinical routine for many applications. Up to now, however, their use is mostly limited to tomographic imaging modalities such as CT or MRI. With very few exceptions, such as fetal ultrasound, classic volume rendering using one-dimensional intensity-based transfer functions fails to yield satisfying results in case of ultrasound volumes. This is particularly due its gradient-like nature, a high amount of noise and speckle, and the fact that individual tissue types are rather characterized by a similar texture than by similar intensity values. Therefore, clinicians still prefer to look at 2D slices extracted from the ultrasound volume. In this work, we present an entirely novel approach to the classification and compositing stage of the volume rendering pipeline, specifically designed for use with ultrasonic images. We introduce point predicates as a generic formulation for integrating the evaluation of not only low-level information like local intensity or gradient, but also of high level information, such as non-local image features or even anatomical models. Thus, we can successfully filter clinically relevant from non-relevant information. In order to effectively reduce the potentially high dimensionality of the predicate configuration space, we propose the predicate histogram as an intuitive user interface. This is augmented by a scribble technique to provide a comfortable metaphor for selecting predicates of interest. Assigning importance factors to the predicates allows for focus-and-context visualization that ensures to always show important (focus) regions of the data while maintaining as much context information as possible. Our method naturally integrates into standard ray casting algorithms and yields superior results in comparison to traditional methods in terms of visualizing a specific target anatomy in ultrasound volumes. PMID- 26356953 TI - ViSlang: A System for Interpreted Domain-Specific Languages for Scientific Visualization. AB - Researchers from many domains use scientific visualization in their daily practice. Existing implementations of algorithms usually come with a graphical user interface (high-level interface), or as software library or source code (low level interface). In this paper we present a system that integrates domain specific languages (DSLs) and facilitates the creation of new DSLs. DSLs provide an effective interface for domain scientists avoiding the difficulties involved with low-level interfaces and at the same time offering more flexibility than high-level interfaces. We describe the design and implementation of ViSlang, an interpreted language specifically tailored for scientific visualization. A major contribution of our design is the extensibility of the ViSlang language. Novel DSLs that are tailored to the problems of the domain can be created and integrated into ViSlang. We show that our approach can be added to existing user interfaces to increase the flexibility for expert users on demand, but at the same time does not interfere with the user experience of novice users. To demonstrate the flexibility of our approach we present new DSLs for volume processing, querying and visualization. We report the implementation effort for new DSLs and compare our approach with Matlab and Python implementations in terms of run-time performance. PMID- 26356954 TI - Interactive Progressive Visualization with Space-Time Error Control. AB - We present a novel scheme for progressive rendering in interactive visualization. Static settings with respect to a certain image quality or frame rate are inherently incapable of delivering both high frame rates for rapid changes and high image quality for detailed investigation. Our novel technique flexibly adapts by steering the visualization process in three major degrees of freedom: when to terminate the refinement of a frame in the background and start a new one, when to display a frame currently computed, and how much resources to consume. We base these decisions on the correlation of the errors due to insufficient sampling and response delay, which we estimate separately using fast yet expressive heuristics. To automate the configuration of the steering behavior, we employ offline video quality analysis. We provide an efficient implementation of our scheme for the application of volume raycasting, featuring integrated GPU-accelerated image reconstruction and error estimation. Our implementation performs an integral handling of the changes due to camera transforms, transfer function adaptations, as well as the progression of the data to in time. Finally, the overall technique is evaluated with an expert study. PMID- 26356955 TI - Vivaldi: A Domain-Specific Language for Volume Processing and Visualization on Distributed Heterogeneous Systems. AB - As the size of image data from microscopes and telescopes increases, the need for high-throughput processing and visualization of large volumetric data has become more pressing. At the same time, many-core processors and GPU accelerators are commonplace, making high-performance distributed heterogeneous computing systems affordable. However, effectively utilizing GPU clusters is difficult for novice programmers, and even experienced programmers often fail to fully leverage the computing power of new parallel architectures due to their steep learning curve and programming complexity. In this paper, we propose Vivaldi, a new domain specific language for volume processing and visualization on distributed heterogeneous computing systems. Vivaldi's Python-like grammar and parallel processing abstractions provide flexible programming tools for non-experts to easily write high-performance parallel computing code. Vivaldi provides commonly used functions and numerical operators for customized visualization and high throughput image processing applications. We demonstrate the performance and usability of Vivaldi on several examples ranging from volume rendering to image segmentation. PMID- 26356956 TI - Multiscale Symmetry Detection in Scalar Fields by Clustering Contours. AB - The complexity in visualizing volumetric data often limits the scope of direct exploration of scalar fields. Isocontour extraction is a popular method for exploring scalar fields because of its simplicity in presenting features in the data. In this paper, we present a novel representation of contours with the aim of studying the similarity relationship between the contours. The representation maps contours to points in a high-dimensional transformation-invariant descriptor space. We leverage the power of this representation to design a clustering based algorithm for detecting symmetric regions in a scalar field. Symmetry detection is a challenging problem because it demands both segmentation of the data and identification of transformation invariant segments. While the former task can be addressed using topological analysis of scalar fields, the latter requires geometry based solutions. Our approach combines the two by utilizing the contour tree for segmenting the data and the descriptor space for determining transformation invariance. We discuss two applications, query driven exploration and asymmetry visualization, that demonstrate the effectiveness of the approach. PMID- 26356957 TI - Low-Pass Filtered Volumetric Shadows. AB - We present a novel and efficient method to compute volumetric soft shadows for interactive direct volume visualization to improve the perception of spatial depth. By direct control of the softness of volumetric shadows, disturbing visual patterns due to hard shadows can be avoided and users can adapt the illumination to their personal and application-specific requirements. We compute the shadowing of a point in the data set by employing spatial filtering of the optical depth over a finite area patch pointing toward each light source. Conceptually, the area patch spans a volumetric region that is sampled with shadow rays; afterward, the resulting optical depth values are convolved with a low-pass filter on the patch. In the numerical computation, however, to avoid expensive shadow ray marching, we show how to align and set up summed area tables for both directional and point light sources. Once computed, the summed area tables enable efficient evaluation of soft shadows for each point in constant time without shadow ray marching and the softness of the shadows can be controlled interactively. We integrated our method in a GPU-based volume renderer with ray casting from the camera, which offers interactive control of the transfer function, light source positions, and viewpoint, for both static and time-dependent data sets. Our results demonstrate the benefit of soft shadows for visualization to achieve user controlled illumination with many-point lighting setups for improved perception combined with high rendering speed. PMID- 26356958 TI - Boundary Aware Reconstruction of Scalar Fields. AB - In visualization, the combined role of data reconstruction and its classification plays a crucial role. In this paper we propose a novel approach that improves classification of different materials and their boundaries by combining information from the classifiers at the reconstruction stage. Our approach estimates the targeted materials' local support before performing multiple material-specific reconstructions that prevent much of the misclassification traditionally associated with transitional regions and transfer function (TF) design. With respect to previously published methods our approach offers a number of improvements and advantages. For one, it does not rely on TFs acting on derivative expressions, therefore it is less sensitive to noisy data and the classification of a single material does not depend on specialized TF widgets or specifying regions in a multidimensional TF. Additionally, improved classification is attained without increasing TF dimensionality, which promotes scalability to multivariate data. These aspects are also key in maintaining low interaction complexity. The results are simple-to-achieve visualizations that better comply with the user's understanding of discrete features within the studied object. PMID- 26356959 TI - Attractive Flicker--Guiding Attention in Dynamic Narrative Visualizations. AB - Focus+context techniques provide visual guidance in visualizations by giving strong visual prominence to elements of interest while the context is suppressed. However, finding a visual feature to enhance for the focus to pop out from its context in a large dynamic scene, while leading to minimal visual deformation and subjective disturbance, is challenging. This paper proposes Attractive Flicker, a novel technique for visual guidance in dynamic narrative visualizations. We first show that flicker is a strong visual attractor in the entire visual field, without distorting, suppressing, or adding any scene elements. The novel aspect of our Attractive Flicker technique is that it consists of two signal stages: The first "orientation stage" is a short but intensive flicker stimulus to attract the attention to elements of interest. Subsequently, the intensive flicker is reduced to a minimally disturbing luminance oscillation ("engagement stage") as visual support to keep track of the focus elements. To find a good trade-off between attraction effectiveness and subjective annoyance caused by flicker, we conducted two perceptual studies to find suitable signal parameters. We showcase Attractive Flicker with the parameters obtained from the perceptual statistics in a study of molecular interactions. With Attractive Flicker, users were able to easily follow the narrative of the visualization on a large display, while the flickering of focus elements was not disturbing when observing the context. PMID- 26356960 TI - Design and Evaluation of Interactive Proofreading Tools for Connectomics. AB - Proofreading refers to the manual correction of automatic segmentations of image data. In connectomics, electron microscopy data is acquired at nanometer-scale resolution and results in very large image volumes of brain tissue that require fully automatic segmentation algorithms to identify cell boundaries. However, these algorithms require hundreds of corrections per cubic micron of tissue. Even though this task is time consuming, it is fairly easy for humans to perform corrections through splitting, merging, and adjusting segments during proofreading. In this paper we present the design and implementation of Mojo, a fully-featured single-user desktop application for proofreading, and Dojo, a multi-user web-based application for collaborative proofreading. We evaluate the accuracy and speed of Mojo, Dojo, and Raveler, a proofreading tool from Janelia Farm, through a quantitative user study. We designed a between-subjects experiment and asked non-experts to proofread neurons in a publicly available connectomics dataset. Our results show a significant improvement of corrections using web-based Dojo, when given the same amount of time. In addition, all participants using Dojo reported better usability. We discuss our findings and provide an analysis of requirements for designing visual proofreading software. PMID- 26356961 TI - Characterizing Molecular Interactions in Chemical Systems. AB - Interactions between atoms have a major influence on the chemical properties of molecular systems. While covalent interactions impose the structural integrity of molecules, noncovalent interactions govern more subtle phenomena such as protein folding, bonding or self assembly. The understanding of these types of interactions is necessary for the interpretation of many biological processes and chemical design tasks. While traditionally the electron density is analyzed to interpret the quantum chemistry of a molecular system, noncovalent interactions are characterized by low electron densities and only slight variations of them- challenging their extraction and characterization. Recently, the signed electron density and the reduced gradient, two scalar fields derived from the electron density, have drawn much attention in quantum chemistry since they enable a qualitative visualization of these interactions even in complex molecular systems and experimental measurements. In this work, we present the first combinatorial algorithm for the automated extraction and characterization of covalent and noncovalent interactions in molecular systems. The proposed algorithm is based on a joint topological analysis of the signed electron density and the reduced gradient. Combining the connectivity information of the critical points of these two scalar fields enables to visualize, enumerate, classify and investigate molecular interactions in a robust manner. Experiments on a variety of molecular systems, from simple dimers to proteins or DNA, demonstrate the ability of our technique to robustly extract these interactions and to reveal their structural relations to the atoms and bonds forming the molecules. For simple systems, our analysis corroborates the observations made by the chemists while it provides new visual and quantitative insights on chemical interactions for larger molecular systems. PMID- 26356962 TI - Ligand Excluded Surface: A New Type of Molecular Surface. AB - The most popular molecular surface in molecular visualization is the solvent excluded surface (SES). It provides information about the accessibility of a biomolecule for a solvent molecule that is geometrically approximated by a sphere. During a period of almost four decades, the SES has served for many purposes - including visualization, analysis of molecular interactions and the study of cavities in molecular structures. However, if one is interested in the surface that is accessible to a molecule whose shape differs significantly from a sphere, a different concept is necessary. To address this problem, we generalize the definition of the SES by replacing the probe sphere with the full geometry of the ligand defined by the arrangement of its van der Waals spheres. We call the new surface ligand excluded surface (LES) and present an efficient, grid-based algorithm for its computation. Furthermore, we show that this algorithm can also be used to compute molecular cavities that could host the ligand molecule. We provide a detailed description of its implementation on CPU and GPU. Furthermore, we present a performance and convergence analysis and compare the LES for several molecules, using as ligands either water or small organic molecules. PMID- 26356963 TI - ADR--Anatomy-Driven Reformation. AB - Dedicated visualization methods are among the most important tools of modern computer-aided medical applications. Reformation methods such as Multiplanar Reformation or Curved Planar Reformation have evolved as useful tools that facilitate diagnostic and therapeutic work. In this paper, we present a novel approach that can be seen as a generalization of Multiplanar Reformation to curved surfaces. The main concept is to generate reformatted medical volumes driven by the individual anatomical geometry of a specific patient. This process generates flat views of anatomical structures that facilitate many tasks such as diagnosis, navigation and annotation. Our reformation framework is based on a non linear as-rigid-as-possible volumetric deformation scheme that uses generic triangular surface meshes as input. To manage inevitable distortions during reformation, we introduce importance maps which allow controlling the error distribution and improving the overall visual quality in areas of elevated interest. Our method seamlessly integrates with well-established concepts such as the slice-based inspection of medical datasets and we believe it can improve the overall efficiency of many medical workflows. To demonstrate this, we additionally present an integrated visualization system and discuss several use cases that substantiate its benefits. PMID- 26356964 TI - Combined Visualization of Wall Thickness and Wall Shear Stress for the Evaluation of Aneurysms. AB - For an individual rupture risk assessment of aneurysms, the aneurysm's wall morphology and hemodynamics provide valuable information. Hemodynamic information is usually extracted via computational fluid dynamic (CFD) simulation on a previously extracted 3D aneurysm surface mesh or directly measured with 4D phase contrast magnetic resonance imaging. In contrast, a noninvasive imaging technique that depicts the aneurysm wall in vivo is still not available. Our approach comprises an experiment, where intravascular ultrasound (IVUS) is employed to probe a dissected saccular aneurysm phantom, which we modeled from a porcine kidney artery. Then, we extracted a 3D surface mesh to gain the vessel wall thickness and hemodynamic information from a CFD simulation. Building on this, we developed a framework that depicts the inner and outer aneurysm wall with dedicated information about local thickness via distance ribbons. For both walls, a shading is adapted such that the inner wall as well as its distance to the outer wall is always perceivable. The exploration of the wall is further improved by combining it with hemodynamic information from the CFD simulation. Hence, the visual analysis comprises a brushing and linking concept for individual highlighting of pathologic areas. Also, a surface clustering is integrated to provide an automatic division of different aneurysm parts combined with a risk score depending on wall thickness and hemodynamic information. In general, our approach can be employed for vessel visualization purposes where an inner and outer wall has to be adequately represented. PMID- 26356965 TI - Visualization of Brain Microstructure Through Spherical Harmonics Illumination of High Fidelity Spatio-Angular Fields. AB - Diffusion kurtosis imaging (DKI) is gaining rapid adoption in the medical imaging community due to its ability to measure the non-Gaussian property of water diffusion in biological tissues. Compared to traditional diffusion tensor imaging (DTI), DKI can provide additional details about the underlying microstructural characteristics of the neural tissues. It has shown promising results in studies on changes in gray matter and mild traumatic brain injury where DTI is often found to be inadequate. The DKI dataset, which has high-fidelity spatio-angular fields, is difficult to visualize. Glyph-based visualization techniques are commonly used for visualization of DTI datasets; however, due to the rapid changes in orientation, lighting, and occlusion, visually analyzing the much more higher fidelity DKI data is a challenge. In this paper, we provide a systematic way to manage, analyze, and visualize high-fidelity spatio-angular fields from DKI datasets, by using spherical harmonics lighting functions to facilitate insights into the brain microstructure. PMID- 26356966 TI - A Robust Parity Test for Extracting Parallel Vectors in 3D. AB - Parallel vectors (PV), the loci where two vector fields are parallel, are commonly used to represent curvilinear features in 3D for data visualization. Methods for extracting PV usually operate on a 3D grid and start with detecting seed points on a cell face. We propose, to the best of our knowledge, the first provably correct test that determines the parity of the number of PV points on a cell face. The test only needs to sample along the face boundary and works for any choice of the two vector fields. A discretization of the test is described, validated, and compared with existing tests that are also based on boundary sampling. The test can guide PV-extraction algorithms to ensure closed curves wherever the input fields are continuous, which we exemplify in extracting ridges and valleys of scalar functions. PMID- 26356967 TI - Vortex Cores of Inertial Particles. AB - The cores of massless, swirling particle motion are an indicator for vortex-like behavior in vector fields and to this end, a number of coreline extractors have been proposed in the literature. Though, many practical applications go beyond the study of the vector field. Instead, engineers seek to understand the behavior of inertial particles moving therein, for instance in sediment transport, helicopter brownout and pulverized coal combustion. In this paper, we present two strategies for the extraction of the corelines that inertial particles swirl around, which depend on particle density, particle diameter, fluid viscosity and gravity. The first is to deduce the local swirling behavior from the autonomous inertial motion ODE, which eventually reduces to a parallel vectors operation. For the second strategy, we use a particle density estimation to locate inertial attractors. With this, we are able to extract the cores of swirling inertial particle motion for both steady and unsteady 3D vector fields. We demonstrate our techniques in a number of benchmark data sets, and elaborate on the relation to traditional massless corelines. PMID- 26356968 TI - FLDA: Latent Dirichlet Allocation Based Unsteady Flow Analysis. AB - In this paper, we present a novel feature extraction approach called FLDA for unsteady flow fields based on Latent Dirichlet allocation (LDA) model. Analogous to topic modeling in text analysis, in our approach, pathlines and features in a given flow field are defined as documents and words respectively. Flow topics are then extracted based on Latent Dirichlet allocation. Different from other feature extraction methods, our approach clusters pathlines with probabilistic assignment, and aggregates features to meaningful topics at the same time. We build a prototype system to support exploration of unsteady flow field with our proposed LDA-based method. Interactive techniques are also developed to explore the extracted topics and to gain insight from the data. We conduct case studies to demonstrate the effectiveness of our proposed approach. PMID- 26356970 TI - Trajectory-Based Flow Feature Tracking in Joint Particle/Volume Datasets. AB - Studying the dynamic evolution of time-varying volumetric data is essential in countless scientific endeavors. The ability to isolate and track features of interest allows domain scientists to better manage large complex datasets both in terms of visual understanding and computational efficiency. This work presents a new trajectory-based feature tracking technique for use in joint particle/volume datasets. While traditional feature tracking approaches generally require a high temporal resolution, this method utilizes the indexed trajectories of corresponding Lagrangian particle data to efficiently track features over large jumps in time. Such a technique is especially useful for situations where the volume dataset is either temporally sparse or too large to efficiently track a feature through all intermediate timesteps. In addition, this paper presents a few other applications of this approach, such as the ability to efficiently track the internal properties of volumetric features using variables from the particle data. We demonstrate the effectiveness of this technique using real world combustion and atmospheric datasets and compare it to existing tracking methods to justify its advantages and accuracy. PMID- 26356969 TI - Advection-Based Sparse Data Management for Visualizing Unsteady Flow. AB - When computing integral curves and integral surfaces for large-scale unsteady flow fields, a major bottleneck is the widening gap between data access demands and the available bandwidth (both I/O and in-memory). In this work, we explore a novel advection-based scheme to manage flow field data for both efficiency and scalability. The key is to first partition flow field into blocklets (e.g. cells or very fine-grained blocks of cells), and then (pre)fetch and manage blocklets on-demand using a parallel key-value store. The benefits are (1) greatly increasing the scale of local-range analysis (e.g. source-destination queries, streak surface generation) that can fit within any given limit of hardware resources; (2) improving memory and I/O bandwidth-efficiencies as well as the scalability of naive task-parallel particle advection. We demonstrate our method using a prototype system that works on workstation and also in supercomputing environments. Results show significantly reduced I/O overhead compared to accessing raw flow data, and also high scalability on a supercomputer for a variety of applications. PMID- 26356971 TI - Visualizing 2-dimensional Manifolds with Curve Handles in 4D. AB - In this paper, we present a mathematical visualization paradigm for exploring curves embedded in 3D and surfaces in 4D mathematical world. The basic problem is that, 3D figures of 4D mathematical entities often twist, turn, and fold back on themselves, leaving important properties behind the surface sheets. We propose an interactive system to visualize the topological features of the original 4D surface by slicing its 3D figure into a series of feature diagram. A novel 4D visualization interface is designed to allow users to control 4D topological shapes via the collection of diagram handles using the established curve manipulation mechanism. Our system can support rich mathematical interaction of 4D mathematical objects which is very difficult with any existing approach. We further demonstrate the effectiveness of the proposed visualization tool using various experimental results and cases studies. PMID- 26356972 TI - Fast and Memory-Efficient Topological Denoising of 2D and 3D Scalar Fields. AB - Data acquisition, numerical inaccuracies, and sampling often introduce noise in measurements and simulations. Removing this noise is often necessary for efficient analysis and visualization of this data, yet many denoising techniques change the minima and maxima of a scalar field. For example, the extrema can appear or disappear, spatially move, and change their value. This can lead to wrong interpretations of the data, e.g., when the maximum temperature over an area is falsely reported being a few degrees cooler because the denoising method is unaware of these features. Recently, a topological denoising technique based on a global energy optimization was proposed, which allows the topology controlled denoising of 2D scalar fields. While this method preserves the minima and maxima, it is constrained by the size of the data. We extend this work to large 2D data and medium-sized 3D data by introducing a novel domain decomposition approach. It allows processing small patches of the domain independently while still avoiding the introduction of new critical points. Furthermore, we propose an iterative refinement of the solution, which decreases the optimization energy compared to the previous approach and therefore gives smoother results that are closer to the input. We illustrate our technique on synthetic and real-world 2D and 3D data sets that highlight potential applications. PMID- 26356973 TI - Conforming Morse-Smale Complexes. AB - Morse-Smale (MS) complexes have been gaining popularity as a tool for feature driven data analysis and visualization. However, the quality of their geometric embedding and the sole dependence on the input scalar field data can limit their applicability when expressing application-dependent features. In this paper we introduce a new combinatorial technique to compute an MS complex that conforms to both an input scalar field and an additional, prior segmentation of the domain. The segmentation constrains the MS complex computation guaranteeing that boundaries in the segmentation are captured as separatrices of the MS complex. We demonstrate the utility and versatility of our approach with two applications. First, we use streamline integration to determine numerically computed basins/mountains and use the resulting segmentation as an input to our algorithm. This strategy enables the incorporation of prior flow path knowledge, effectively resulting in an MS complex that is as geometrically accurate as the employed numerical integration. Our second use case is motivated by the observation that often the data itself does not explicitly contain features known to be present by a domain expert. We introduce edit operations for MS complexes so that a user can directly modify their features while maintaining all the advantages of a robust topology-based representation. PMID- 26356974 TI - Escape Maps. AB - We present a technique to visualize the streamline-based mapping between the boundary of a simply-connected subregion of arbitrary 3D vector fields. While the streamlines are seeded on one part of the boundary, the remaining part serves as escape border. Hence, the seeding part of the boundary represents a map of streamline behavior, indicating if streamlines reach the escape border or not. Since the resulting maps typically exhibit a very fine and complex structure and are thus not amenable to direct sampling, our approach instead aims at topologically consistent extraction of their boundary. We show that isocline surfaces of the projected vector field provide a robust basis for stream-surface based extraction of these boundaries. The utility of our technique is demonstrated in the context of transport processes using vector field data from different domains. PMID- 26356975 TI - Visualization of Regular Maps: The Chase Continues. AB - A regular map is a symmetric tiling of a closed surface, in the sense that all faces, vertices, and edges are topologically indistinguishable. Platonic solids are prime examples, but also for surfaces with higher genus such regular maps exist. We present a new method to visualize regular maps. Space models are produced by matching regular maps with target shapes in the hyperbolic plane. The approach is an extension of our earlier work. Here a wider variety of target shapes is considered, obtained by duplicating spherical and toroidal regular maps, merging triangles, punching holes, and gluing the edges. The method produces about 45 new examples, including the genus 7 Hurwitz surface. PMID- 26356976 TI - City Forensics: Using Visual Elements to Predict Non-Visual City Attributes. AB - We present a method for automatically identifying and validating predictive relationships between the visual appearance of a city and its non-visual attributes (e.g. crime statistics, housing prices, population density etc.). Given a set of street-level images and (location, city-attribute-value) pairs of measurements, we first identify visual elements in the images that are discriminative of the attribute. We then train a predictor by learning a set of weights over these elements using non-linear Support Vector Regression. To perform these operations efficiently, we implement a scalable distributed processing framework that speeds up the main computational bottleneck (extracting visual elements) by an order of magnitude. This speedup allows us to investigate a variety of city attributes across 6 different American cities. We find that indeed there is a predictive relationship between visual elements and a number of city attributes including violent crime rates, theft rates, housing prices, population density, tree presence, graffiti presence, and the perception of danger. We also test human performance for predicting theft based on street-level images and show that our predictor outperforms this baseline with 33% higher accuracy on average. Finally, we present three prototype applications that use our system to (1) define the visual boundary of city neighborhoods, (2) generate walking directions that avoid or seek out exposure to city attributes, and (3) validate user-specified visual elements for prediction. PMID- 26356977 TI - Using Topological Analysis to Support Event-Guided Exploration in Urban Data. AB - The explosion in the volume of data about urban environments has opened up opportunities to inform both policy and administration and thereby help governments improve the lives of their citizens, increase the efficiency of public services, and reduce the environmental harms of development. However, cities are complex systems and exploring the data they generate is challenging. The interaction between the various components in a city creates complex dynamics where interesting facts occur at multiple scales, requiring users to inspect a large number of data slices over time and space. Manual exploration of these slices is ineffective, time consuming, and in many cases impractical. In this paper, we propose a technique that supports event-guided exploration of large, spatio-temporal urban data. We model the data as time-varying scalar functions and use computational topology to automatically identify events in different data slices. To handle a potentially large number of events, we develop an algorithm to group and index them, thus allowing users to interactively explore and query event patterns on the fly. A visual exploration interface helps guide users towards data slices that display interesting events and trends. We demonstrate the effectiveness of our technique on two different data sets from New York City (NYC): data about taxi trips and subway service. We also report on the feedback we received from analysts at different NYC agencies. PMID- 26356978 TI - Trend-Centric Motion Visualization: Designing and Applying a New Strategy for Analyzing Scientific Motion Collections. AB - In biomechanics studies, researchers collect, via experiments or simulations, datasets with hundreds or thousands of trials, each describing the same type of motion (e.g., a neck flexion-extension exercise) but under different conditions (e.g., different patients, different disease states, pre- and post-treatment). Analyzing similarities and differences across all of the trials in these collections is a major challenge. Visualizing a single trial at a time does not work, and the typical alternative of juxtaposing multiple trials in a single visual display leads to complex, difficult-to-interpret visualizations. We address this problem via a new strategy that organizes the analysis around motion trends rather than trials. This new strategy matches the cognitive approach that scientists would like to take when analyzing motion collections. We introduce several technical innovations making trend-centric motion visualization possible. First, an algorithm detects a motion collection's trends via time-dependent clustering. Second, a 2D graphical technique visualizes how trials leave and join trends. Third, a 3D graphical technique, using a median 3D motion plus a visual variance indicator, visualizes the biomechanics of the set of trials within each trend. These innovations are combined to create an interactive exploratory visualization tool, which we designed through an iterative process in collaboration with both domain scientists and a traditionally-trained graphic designer. We report on insights generated during this design process and demonstrate the tool's effectiveness via a validation study with synthetic data and feedback from expert musculoskeletal biomechanics researchers who used the tool to analyze the effects of disc degeneration on human spinal kinematics. PMID- 26356979 TI - Curve Boxplot: Generalization of Boxplot for Ensembles of Curves. AB - In simulation science, computational scientists often study the behavior of their simulations by repeated solutions with variations in parameters and/or boundary values or initial conditions. Through such simulation ensembles, one can try to understand or quantify the variability or uncertainty in a solution as a function of the various inputs or model assumptions. In response to a growing interest in simulation ensembles, the visualization community has developed a suite of methods for allowing users to observe and understand the properties of these ensembles in an efficient and effective manner. An important aspect of visualizing simulations is the analysis of derived features, often represented as points, surfaces, or curves. In this paper, we present a novel, nonparametric method for summarizing ensembles of 2D and 3D curves. We propose an extension of a method from descriptive statistics, data depth, to curves. We also demonstrate a set of rendering and visualization strategies for showing rank statistics of an ensemble of curves, which is a generalization of traditional whisker plots or boxplots to multidimensional curves. Results are presented for applications in neuroimaging, hurricane forecasting and fluid dynamics. PMID- 26356980 TI - Volume-Preserving Mapping and Registration for Collective Data Visualization. AB - In order to visualize and analyze complex collective data, complicated geometric structure of each data is desired to be mapped onto a canonical domain to enable map-based visual exploration. This paper proposes a novel volume-preserving mapping and registration method which facilitates effective collective data visualization. Given two 3-manifolds with the same topology, there exists a mapping between them to preserve each local volume element. Starting from an initial mapping, a volume restoring diffeomorphic flow is constructed as a compressible flow based on the volume forms at the manifold. Such a flow yields equality of each local volume element between the original manifold and the target at its final state. Furthermore, the salient features can be used to register the manifold to a reference template by an incompressible flow guided by a divergence-free vector field within the manifold. The process can retain the equality of local volume elements while registering the manifold to a template at the same time. An efficient and practical algorithm is also presented to generate a volume-preserving mapping and a salient feature registration on discrete 3D volumes which are represented with tetrahedral meshes embedded in 3D space. This method can be applied to comparative analysis and visualization of volumetric medical imaging data across subjects. We demonstrate an example application in multimodal neuroimaging data analysis and collective data visualization. PMID- 26356981 TI - Fixed-Rate Compressed Floating-Point Arrays. AB - Current compression schemes for floating-point data commonly take fixed-precision values and compress them to a variable-length bit stream, complicating memory management and random access. We present a fixed-rate, near-lossless compression scheme that maps small blocks of 4(d) values in d dimensions to a fixed, user specified number of bits per block, thereby allowing read and write random access to compressed floating-point data at block granularity. Our approach is inspired by fixed-rate texture compression methods widely adopted in graphics hardware, but has been tailored to the high dynamic range and precision demands of scientific applications. Our compressor is based on a new, lifted, orthogonal block transform and embedded coding, allowing each per-block bit stream to be truncated at any point if desired, thus facilitating bit rate selection using a single compression scheme. To avoid compression or decompression upon every data access, we employ a software write-back cache of uncompressed blocks. Our compressor has been designed with computational simplicity and speed in mind to allow for the possibility of a hardware implementation, and uses only a small number of fixed-point arithmetic operations per compressed value. We demonstrate the viability and benefits of lossy compression in several applications, including visualization, quantitative data analysis, and numerical simulation. PMID- 26356982 TI - Decomposition and Simplification of Multivariate Data using Pareto Sets. AB - Topological and structural analysis of multivariate data is aimed at improving the understanding and usage of such data through identification of intrinsic features and structural relationships among multiple variables. We present two novel methods for simplifying so-called Pareto sets that describe such structural relationships. Such simplification is a precondition for meaningful visualization of structurally rich or noisy data. As a framework for simplification operations, we introduce a decomposition of the data domain into regions of equivalent structural behavior and the reachability graph that describes global connectivity of Pareto extrema. Simplification is then performed as a sequence of edge collapses in this graph; to determine a suitable sequence of such operations, we describe and utilize a comparison measure that reflects the changes to the data that each operation represents. We demonstrate and evaluate our methods on synthetic and real-world examples. PMID- 26356983 TI - Multi-Charts for Comparative 3D Ensemble Visualization. AB - A comparative visualization of multiple volume data sets is challenging due to the inherent occlusion effects, yet it is important to effectively reveal uncertainties, correlations and reliable trends in 3D ensemble fields. In this paper we present bidirectional linking of multi-charts and volume visualization as a means to analyze visually 3D scalar ensemble fields at the data level. Multi charts are an extension of conventional bar and line charts: They linearize the 3D data points along a space-filling curve and draw them as multiple charts in the same plot area. The bar charts encode statistical information on ensemble members, such as histograms and probability densities, and line charts are overlayed to allow comparing members against the ensemble. Alternative linearizations based on histogram similarities or ensemble variation allow clustering of spatial locations depending on data distribution. Multi-charts organize the data at multiple scales to quickly provide overviews and enable users to select regions exhibiting interesting behavior interactively. They are further put into a spatial context by allowing the user to brush or query value intervals and specific distributions, and to simultaneously visualize the corresponding spatial points via volume rendering. By providing a picking mechanism in 3D and instantly highlighting the corresponding data points in the chart, the user can go back and forth between the abstract and the 3D view to focus the analysis. PMID- 26356984 TI - Stent Maps--Comparative Visualization for the Prediction of Adverse Events of Transcatheter Aortic Valve Implantations. AB - Transcatheter aortic valve implantation (TAVI) is a minimally-invasive method for the treatment of aortic valve stenosis in patients with high surgical risk. Despite the success of TAVI, side effects such as paravalvular leakages can occur postoperatively. The goal of this project is to quantitatively analyze the co occurrence of this complication and several potential risk factors such as stent shape after implantation, implantation height, amount and distribution of calcifications, and contact forces between stent and surrounding structure. In this paper, we present a two-dimensional visualization (stent maps), which allows (1) to comprehensively display all these aspects from CT data and mechanical simulation results and (2) to compare different datasets to identify patterns that are typical for adverse effects. The area of a stent map represents the surface area of the implanted stent - virtually straightened and uncoiled. Several properties of interest, like radial forces or stent compression, are displayed in this stent map in a heatmap-like fashion. Important anatomical landmarks and calcifications are plotted to show their spatial relation to the stent and possible correlations with the color-coded parameters. To provide comparability, the maps of different patient datasets are spatially adjusted according to a corresponding anatomical landmark. Also, stent maps summarizing the characteristics of different populations (e.g. with or without side effects) can be generated. Up to this point several interesting patterns have been observed with our technique, which remained hidden when examining the raw CT data or 3D visualizations of the same data. One example are obvious radial force maxima between the right and non-coronary valve leaflet occurring mainly in cases without leakages. These observations confirm the usefulness of our approach and give starting points for new hypotheses and further analyses. Because of its reduced dimensionality, the stent map data is an appropriate input for statistical group evaluation and machine learning methods. PMID- 26356985 TI - Management of varicella-zoster virus primary infection during pregnancy: A national survey of practice. AB - BACKGROUND: Varicella (VZV) infection in pregnancy can result in serious outcomes: maternal pneumoniae irrespective of the term of pregnancy, and lead to congenital varicella syndrome before 18 weeks of gestation and neonatal varicella. There are between 350 and 500 cases a year in France. Until now, there have been no scientific obstetrical guidelines for clinical practice in France for VZV infection during pregnancy. OBJECTIVES: To evaluate health care providers' knowledge and practices concerning varicella infection during pregnancy in France. STUDY DESIGN: An anonymous survey on VZV infection was sent by e-mail to gynecologists-obstetricians and midwives. We evaluated their knowledge and practices concerning VZV transmission, maternal varicella, congenital varicella syndrome, neonatal varicella and prevention. RESULTS: The survey was completed by 271 professionals: gynecologists (161/271; 60%) and midwives (110/271; 40%). Among 20 items, 5 were multiple choice questions. 29 correct answers were expected. Scores ranged from 6/29 to 28/29 (mean score: 17.44/29). CONCLUSIONS: The consequences of VZV primary infection in pregnancy are poorly known. We reveal a diversity of management among practitioners in our study population, not always in accordance with the international scientific literature or with the guidelines of other countries. Health care providers should update their knowledge of varicella infection during pregnancy. The publication of national guidelines could help to achieve this objective. PMID- 26356986 TI - Emergence of Norovirus GII.4 variants in acute gastroenteritis outbreaks in South Korea between 2006 and 2013. AB - BACKGROUND: New emerging strains of noroviruses (NoVs) often increase acute gastroenteritis (AGE) outbreaks worldwide. OBJECTIVE: We analyzed the epidemiological features and genotypic patterns of NoVs in AGE outbreaks. STUDY DESIGN: To elucidate the public health impact of NoVs during AGE outbreaks in South Korea, a molecular and epidemiological investigation was performed with 318 AGE outbreaks reported from the Gyeonggi province of South Korea during the period from 2006 to 2013. RESULTS: NoVs were associated with 102 (32.1%) of the AGE outbreaks. Epidemiological data revealed that the majority of NoV outbreaks were in the student group (47.1%), and the majority of AGE patients were identified in schools (68.8%). NoV genogroup (G) II strains were associated with 94 (92.2%) of the NoV outbreaks, and GII.4 strains were predominantly associated with 57.6% (n=49) of NoV GII outbreaks. Four GII.4 variants (2006b, 2007, 2009 and 2012 variants) emerged and showed different contributions to NoV outbreak activity. The 2006b variant was predominantly associated with NoV outbreaks during the early years of the study period, and was subsequently displaced by the New Orleans 2009 variant, and most recently by the Sydney 2012 variant. In addition, the GII.2, GII.14, and GII.17 strains have recently been often associated with NoV AGE outbreaks. CONCLUSIONS: The emergence of new NoV GII.4 variants significantly affected the NoV outbreak activity in South Korea during the period from 2006 to 2013. The surveillance for new emerging strains affecting NoV outbreak activity should be intensified to develop an adequate policy to prevent further NoV outbreaks. PMID- 26356987 TI - Hepatitis B viral load in dried blood spots: A validation study in Zambia. AB - BACKGROUND: Access to hepatitis B viral load (VL) testing is poor in sub-Saharan Africa (SSA) due to economic and logistical reasons. OBJECTIVES: To demonstrate the feasibility of testing dried blood spots (DBS) for hepatitis B virus (HBV) VL in a laboratory in Lusaka, Zambia, and to compare HBV VLs between DBS and plasma samples. STUDY DESIGN: Paired plasma and DBS samples from HIV-HBV co-infected Zambian adults were analyzed for HBV VL using the COBAS AmpliPrep/COBAS TaqMan HBV test (Version 2.0) and for HBV genotype by direct sequencing. We used Bland Altman analysis to compare VLs between sample types and by genotype. Logistic regression analysis was conducted to assess the probability of an undetectable DBS result by plasma VL. RESULTS: Among 68 participants, median age was 34 years, 61.8% were men, and median plasma HBV VL was 3.98logIU/ml (interquartile range, 2.04-5.95). Among sequenced viruses, 28 were genotype A1 and 27 were genotype E. Bland-Altman plots suggested strong agreement between DBS and plasma VLs. DBS VLs were on average 1.59logIU/ml lower than plasma with 95% limits of agreement of 2.40 to -0.83log IU/ml. At a plasma VL >=2,000IU/ml, the probability of an undetectable DBS result was 1.8% (95% CI: 0.5-6.6). At plasma VL >=20,000IU/ml this probability reduced to 0.2% (95% CI: 0.03-1.7). CONCLUSIONS: In a Zambian laboratory, we observed strong agreement between DBS and plasma VLs and high sensitivity in DBS at plasma VL >=2,000IU/ml. As HBV treatment expands, DBS could increase access to HBV VL testing and care in SSA settings. PMID- 26356989 TI - Quantifying Wheelchair Basketball Match Load: A Comparison of Heart-Rate and Perceived-Exertion Methods. AB - PURPOSE: To describe the objective and subjective match load (ML) of wheelchair basketball (WB) and determine the relationship between session heart-rate (HR) based ML and rating-of-perceived-exertion (RPE) -based ML methods. METHODS: HR based measurements of ML included Edwards ML and Stagno training impulses (TRIMPMOD), while RPE-based ML measurements included respiratory (sRPEres) and muscular (sRPEmus). Data were collected from 10 WB players during a whole competitive season. RESULTS: Edwards ML and TRIMPMOD averaged across 16 matches were 255.3 +/- 66.3 and 167.9 +/- 67.1 AU, respectively. In contrast, sRPEres ML and sRPEmus ML were found to be higher (521.9 +/- 188.7 and 536.9 +/- 185.8 AU, respectively). Moderate correlations (r = .629-.648, P < .001) between Edwards ML and RPE-based ML methods were found. Moreover, similar significant correlations were also shown between the TRIMPMOD and RPE-based ML methods (r = .627-.668, P < .001). That said, only >=40% of variance in HR-based ML was explained by RPE based ML, which could be explained by the heterogeneity of physical-impairment type. CONCLUSION: RPE-based ML methods could be used as an indicator of global internal ML in highly trained WB players. PMID- 26356990 TI - Variants of early-onset restrictive eating disturbances in middle childhood. AB - OBJECTIVE: This study sought to determine the factor structure of the newly developed self-report screening questionnaire Eating Disturbances in Youth Questionnaire (EDY-Q) as well as to report the distribution of variants of early onset restrictive eating disturbances characteristic of avoidant/restrictive food intake disorder (ARFID) in a middle childhood population sample. METHOD: Using the EDY-Q, a total of 1,444 children aged 8-13 years were screened in elementary schools in Switzerland via self-report. The factor analysis of the 12 items covering ARFID related symptoms was performed using a principal component analysis (PCA). RESULTS: The PCA showed a four factor solution, with clear allocation to the scales covering three variants of early-onset restrictive eating disturbances and weight problems. Inadequate overall food intake was reported by 19.3% of the children, a limited accepted amount of food by 26.1%, and food avoidance based on a specific underlying fear by 5.0%. DISCUSSION: The postulated factor structure of the EDY-Q was confirmed, further supporting the existence of distinct variants of early-onset restrictive eating disturbances. Avoidant/restrictive eating behavior seems to be a common experience in middle childhood, but results have to be confirmed using validated interviews. PMID- 26356988 TI - Dynamic expression of transcription factor Brn3b during mouse cranial nerve development. AB - During development, transcription factor combinatorial codes define a large variety of morphologically and physiologically distinct neurons. Such a combinatorial code has been proposed for the differentiation of projection neurons of the somatic and visceral components of cranial nerves. It is possible that individual neuronal cell types are not specified by unique transcription factors but rather emerge through the intersection of their expression domains. Brn3a, Brn3b, and Brn3c, in combination with each other and/or transcription factors of other families, can define subgroups of retinal ganglion cells (RGC), spiral and vestibular ganglia, inner ear and vestibular hair cell neurons in the vestibuloacoustic system, and groups of somatosensory neurons in the dorsal root ganglia. The present study investigates the expression and potential role of the Brn3b transcription factor in cranial nerves and associated nuclei of the brainstem. We report the dynamic expression of Brn3b in the somatosensory component of cranial nerves II, V, VII, and VIII and visceromotor nuclei of nerves VII, IX, and X as well as other brainstem nuclei during different stages of development into adult stage. We find that genetically identified Brn3b(KO) RGC axons show correct but delayed pathfinding during the early stages of embryonic development. However, loss of Brn3b does not affect the anatomy of the other cranial nerves normally expressing this transcription factor. PMID- 26356991 TI - Copper Accumulates in Hemosiderins in Livers of Patients with Iron Overload Syndromes. AB - In biology, redox reactions are essential and sometimes harmful, and therefore, iron metabolism is tightly regulated by cuproproteins. Since the state of copper in iron overload syndromes remains unclear, we investigated whether copper metabolism is altered in these syndromes. Eleven patients with iron overload syndromes participated in this study. The clinical diagnoses were aceruloplasminemia (n=2), hemochromatosis (n=5), ferroportin disease (n=2), and receiving excess intravenous iron supplementation (n=2). Liver specimens were analyzed using a light microscope and transmission electron microscope equipped with an X-ray analyzer. In addition to a large amount of iron associated with oxygen and phosphorus, the iron-rich hemosiderins of hepatocytes and Kupffer cells contained small amounts of copper and sulfur, regardless of disease etiology. Two-dimensional imaging clearly showed that cuproproteins were distributed homogenously with iron complexes within hemosiderins. Copper stasis was unlikely in noncirrhotic patients. The enhanced induction of cuproproteins by excess iron may contribute to copper accumulation in hemosiderins. In conclusion, we have demonstrated that copper accumulates in hemosiderins in iron overload conditions, perhaps due to alterations in copper metabolism. PMID- 26356992 TI - Use of Triple Microcatheters for Endovascular Treatment of Wide-Necked Intracranial Aneurysms: A Single Center Experience. AB - OBJECTIVE: The dual microcatheter technique is common practice for coil embolization of a wide-necked aneurysm, due to safety and efficacy. However, technical limitations of some complex configurations may necessitate additional microcatheters to bolster coil stability, compact the coil, or for protection. Described herein is a triple microcatheter technique for endovascular management of wide-necked intracranial aneurysms. MATERIALS AND METHODS: Data accruing prospectively between January 2006 and October 2014 on simultaneously executed triple microcatheter coil embolization procedures done in 38 saccular aneurysms were reviewed. Clinical and morphological outcomes were assessed, with emphasis on technical aspects of treatment. RESULTS: The triple microcatheter technique was successfully applied to all 38 saccular aneurysms, involving the posterior communicating artery (n = 13), the middle cerebral artery (n = 10), the basilar tip (n = 7), the anterior cerebral artery (n = 5), and the internal carotid artery (n = 3). Stent protection was added in four patients and balloon remodeling in one. Dual microcatheters (n = 24) were usually deployed to deliver the coil within sacs of aneurysms, with the additional microcatheter used for protection. Otherwise, triple microcatheters were deployed for coil delivery (n = 11) or coils were delivered via a single microcatheter, with dual microcatheters deployed for protection (n = 3). Successful occlusion of aneurysms was achieved in 89.5% of cases, with no procedure-related morbidity or mortality. Stable occlusion was maintained in 72.2% (26/36) of the aneurysms at the final follow-up (mean interval, 30.2 +/- 22.7 months). CONCLUSION: The outcomes of this limited study suggest that the triple microcatheter technique may be an effective and safe therapeutic option for wide-necked aneurysms, using technical strategies tailored to complex angio-anatomic configurations. PMID- 26356993 TI - Adapting SWAT hillslope erosion model to predict sediment concentrations and yields in large Basins. AB - The Soil and Water Assessment Tool (SWAT) is used worldwide for water quality assessment and planning. This paper aimed to assess and adapt SWAT hillslope sediment yield model (Modified Universal Soil Loss Equation, MUSLE) for applications in large basins, i.e. when spatial data is coarse and model units are large; and to develop a robust sediment calibration method for large regions. The Upper Danube Basin (132,000km(2)) was used as case study representative of large European Basins. The MUSLE was modified to reduce sensitivity of sediment yields to the Hydrologic Response Unit (HRU) size, and to identify appropriate algorithms for estimating hillslope length (L) and slope-length factor (LS). HRUs gross erosion was broadly calibrated against plot data and soil erosion map estimates. Next, mean annual SWAT suspended sediment concentrations (SSC, mg/L) were calibrated and validated against SSC data at 55 gauging stations (622 station-years). SWAT annual specific sediment yields in subbasin reaches (RSSY, t/km(2)/year) were compared to yields measured at 33 gauging stations (87station years). The best SWAT configuration combined a MUSLE equation modified by the introduction of a threshold area of 0.01km(2) where L and LS were estimated with flow accumulation algorithms. For this configuration, the SSC residual interquartile was less than +/-15mg/L both for the calibration (1995-2004) and the validation (2005-2009) periods. The mean SSC percent bias for 1995-2009 was 24%. RSSY residual interquartile was within +/-10t/km(2)/year, with a mean RSSY percent bias of 12%. Residuals showed no bias with respect to drainage area, slope, or spatial distribution. The use of multiple data types at multiple sites enabled robust simulation of sediment concentrations and yields of the region. The MUSLE modifications are recommended for use in large basins. Based on SWAT simulations, we present a sediment budget for the Upper Danube Basin. PMID- 26356994 TI - In situ evaluation of wastewater discharges and the bioavailability of contaminants to marine biota. AB - Marine sediment quality of wastewater discharges areas was determined by using in situ caged clams Ruditapes philippinarum taking into account the seasonality. Clams were caged in sediment directly affected by wastewater discharges at four sites (P1, P2, P3, P4) at the Bay of Cadiz (SW, Spain), and one reference site (P6). Exposure to contaminated sediments was confirmed by measurement of metals and As, PAH, pharmaceutical products and surfactants (SAS) in bottom sediments. Biological effects were determined by following biomarkers of exposure (activities of 7-ethoxyresorufin O-deethylase - EROD, dibenzylfluorescein dealkylase - DBF, glutathione S-transferase - GST, glutathione peroxidase - GPX, glutathione reductase - GR and acetylcholinesterase - AChE), effects (lysosomal membrane stability - LMS, DNA damage and lipid peroxidation - LPO), energy status (total lipids - TLP and mitochondrial electron transport - MET), and involved in the mode of action of pharmaceutical products (monoamine oxidase activity - MAO, alkali-labile phosphates - ALP levels and cyclooxygenase activity - COX). In winter, urban effluents were detoxified by phase I biotransformation (CYP3A-like activity), phase II (GST), and the activation of antioxidant defence enzymes (GR). Urban effluents lead to the detoxification metabolism (CYP1A-like), oxidative effects (LPO and DNA damage), neurotoxicity (AChE) and neuroendocrine disruption (COX and ALP levels) involved in inflammation (P1 and P2) and changes in reproduction as spawning delay (P3 and P4) in clams exposed in summer. Adverse effects on biota exposed to sediment directly affected by wastewater discharges depend on the chemical contamination level and also on the reproductive cycle according to seasonality. PMID- 26356996 TI - Cisplatin and Paclitaxel Alter the Expression Pattern of miR-143/145 and miR 183/96/182 Clusters in T24 Bladder Cancer Cells. AB - Although cisplatin-based chemotherapy is considered to be the treatment of choice for metastatic bladder cancer, its efficacy and tolerability has proven to be limited. MicroRNAs are small noncoding RNAs, whose genes are frequently organized in clusters. These molecules constitute posttranscriptional regulators of mRNA expression and are claimed to be deregulated in cancer. miR-143/145 and miR 183/96/182 clusters have been extensively studied in bladder cancer cells. Herein, we tried to add up to this knowledge by assessing the expression levels of the five mature microRNAs derived from the aforementioned clusters in T24 bladder cancer cells exposed to either cisplatin or paclitaxel. For both compounds, the viability of treated T24 cells was estimated via the MTT colorimetric assay and the Trypan Blue exclusion method, while a fraction of the cells was left to recover. The expression levels of all mature microRNAs were finally quantified both in treated and in recovered cells by performing real-time PCR. According to our data, cisplatin and paclitaxel strongly decreased T24 cells' viability, showing in parallel the ability to significantly down-regulate miR-143 levels, and up-regulate the expression levels of miR-145, miR-183, miR 96, and miR-182, which, in their total, demonstrated case-specific variations after recovery period. PMID- 26356997 TI - Work-related respiratory symptoms in Champagne vineyard workers. AB - BACKGROUND: Vineyard workers (VW) are exposed to various respiratory allergens. The aims of the study were to determine the prevalence of work related respiratory symptoms (WRS) in Champagne VW in France and to analyze the relationships between symptoms, occupational exposure and sensitization profile. METHODS: VW of Reims area were prospectively recruited between 2007 and 2010. Demographic and occupational characteristics were recorded. Respiratory symptoms were scored for each month of the past year. Results of respiratory functional tests and skin prick tests for common respiratory allergens, grape moulds and vine pollen were recorded. RESULTS: 307 subjects were included. The prevalence of WRS was 11%. Compared to subjects with symptoms unrelated to work, subjects with WRS were more frequently sensitized to gramineae (34% vs 18%, p = 0.05), described ocular itching (74% vs 37%, p < 0.001) and seasonal symptoms (88% vs 69%, p = 0.03) mainly during lifting and trellising (57% vs 17%, p < 0.001). CONCLUSION: WRS are frequent in Champagne WV and are associated with a sensitization to gramineae and with activities performed close to vine in late spring. PMID- 26356998 TI - Pre-co-seasonal Allergen Immunotherapy in Parietaria allergic patients. AB - BACKGROUND: Even though the Parietaria pollen season may be rather long, many physicians think that Parietaria pollen is a perennial allergen present along the whole year. In fact, many doctors prefer to prescribe allergen immunotherapy (AIT) in Parietaria allergic patients, using continuous courses. On the other hand, physicians usually prescribe pre-co-seasonal AIT course for other pollen allergies. OBJECTIVE: This study aimed at investigating whether a single pre-co seasonal AIT course could be effective in Parietaria allergic patients. METHODS: Globally, 59 subjects (31 males, mean age 35.9 years) were retrospectively evaluated. All were treated with SLIT as a pre-co-seasonal course: 33 with Parietaria extract and 26 with birch extract. Patients' perception of symptom severity and medication use was assessed by visual analogue scale, comparing the previous pollen season and the present. RESULTS: The Parietaria 2012 pollen season started from the 60(th) day and ended at the 205(th) day of 2012. A single pre-co-seasonal SLIT course was able to significantly (p < 0.0001) reduce symptom severity and medication use. CONCLUSION: This preliminary study demonstrates that Parietaria pollen season in Genoa lasted about six months and a single pre-co seasonal SLIT Parietaria course could be sufficient to reduce symptom severity and medication use. PMID- 26356999 TI - Different allergenicity of pollen extracts of three Mediterranean cypress species accounted for cytological observations. AB - BACKGROUND: Cypresses play an important role in the urban landscape of the Mediterranean region, releasing a huge amount of allergenic airborne pollen which causes a specific pollinosis in exposed people. OBJECTIVE: The aim of this work is to evaluate, in vivo and in vitro, the potential allergenicity of Cupressus macrocarpa pollen, and to compare it with the allergenicity observed for C. arizonica and C. sempervirens. METHODS: Pollen extracts of the three species were prepared, to determine their protein profile through SDS PAGE analysis and to evaluate their allergenic potential through EAST inhibition assays and SPT. Pollen grain composition was evaluated using a cytochemical approach with optical microscopy. RESULTS: SDS PAGE, EAST inhibition and SPT indicated the higher allergenic potential of C. arizonica compared to C. sempervirens and C. macrocarpa. No significant differences in allergenic potential were found between the latter two species. Cytochemical observations reveal higher beta-glucans and protein content in the intine of C. arizonica during hydration. CONCLUSION: The higher protein content found in C. arizonica pollen grains extract may be due to higher enzyme activity leading to the movement of beta-glucans and pectins from the intine to the partially developed pollen cell wall during hydration. This could explain the higher potential allergenicity of C.arizonica in respect to C. macrocarpa and C. sempervirens. PMID- 26357000 TI - IL-31 and IL-33 circulating levels in allergic contact dermatitis. AB - Enhanced IL-31 expression in skin biopsies is present in allergic contact dermatitis (ACD). IL-33 expression is induced in keratinocytes and in skin of ACD patients. This overexpression is present in both allergic and irritant conditions. The aim of this work was to test the systemic involvement of IL-31 and IL-33 in ACD. IL-31 levels were significantly higher in patients than in controls. IL-33 serum levels, on the contrary, were similar in patients and controls. This work shows a possible systemic involvement of IL-31 and the absence of a systemic involvement of IL-33 in ACD. IL-31 levels do not seem related to the allergen involved, and did not change on the strength of the allergen involved. More likely, IL-31 levels are related to the itch. IL-33, instead, is secreted from damaged or inflamed tissue and might function as an early warning system at the site of skin damage. In the future, IL-31 could be a possible therapeutic target of all pruritic skin diseases resistant to conventional therapies. PMID- 26357001 TI - Delayed Anaphylaxis to the flu vaccine unrelated to known non-viral components. AB - On February 4, 2010 the CDC's Advisory Committee on Immunization Practices voted for universal flu vaccination to expand protection against the flu throughout the United States. In addition to this administration expansion, six new influenza vaccines have been introduced into the market possibly introducing new allergenic potentials. We report two cases of delayed anaphylaxis to the flu vaccine. PMID- 26357002 TI - Alpha-gal anaphylaxis: the first case report in Italy. AB - We report the case of a 55-year-old man who went into anaphylactic shock six hours after eating a meal containing meat. He reported having had several tick bites in months before the reaction. The serum specific IgE showed strong positivity to alpha-gal. This is clearly alpha-gal anaphylaxis with delayed onset after meat ingestion caused by tick bite, confirmed by alpha-gal IgE positivity. PMID- 26357003 TI - What could be the role of molecular-based allergy diagnostics in detecting the risk of developing allergic sensitization to furry animals? AB - Although this highly refined diagnostic approach has been used in several fields of allergy diagnosis, we noticed the scarcity of data on the role of CDR in detecting current sensitization to the allergens of common pets (cat / dog) and, especially, its potential usefulness in predicting the risk of sensitization to other furry animals. Reported data suggest that cross-reacting mechanisms might play an important role in a significant proportion of allergic sensitizations to furry animals (common pets and unusual / exotic mammals) especially in the absence of any possible direct / indirect contact. In this context an evaluation of specific IgE by using the micro-array technique ImmunoCAP ISAC (Thermofisher Scientific - Immuno-Diagnostics, Sweden) for lipocalins (Can f 1, Can f 2, Equ c 1, Fel d 4, Mus m 1) and albumins (Bos d 6, Can f 3, Equ c 3, Fel d 2) might be very useful to evaluate the possibility of cross-reactions between the allergens of different animals. In fact, allergic sensitization without animal exposure is a relevant risk for patients, because they are not aware about the possibility that even severe respiratory symptoms may develop after an occasional animal contact. This aspect should be taken into account by susceptible individuals before acquiring new pets, after removal of common pets or beginning a contact for working / leisure activity with a common as well as uncommon animal. PMID- 26357004 TI - Is Shift Work Associated with Lipid Disturbances and Increased Insulin Resistance? AB - OBJECTIVE: Shift work is associated with higher risk of metabolic disturbances and cardiovascular diseases. There are contradictory reports on the effect of shift work on lipid parameters in the literature. No studies have investigated any possible association between shift work and the ratio of serum triglyceride to high density lipoprotein cholesterol (TG/HDL-C ratio). This ratio can be used as a predictor for insulin resistance. The main aim of the present cross sectional study was to investigate the association between shift work and serum TG/HDL-C ratio, TG level, and HDL-C level. METHODS: One hundred and forty adult Jordanian employees were recruited. Demographic data, lifestyle habits, clinical parameters, and working patterns data were documented through a well-structured questionnaire. Serum TG and HDL-C levels were measured after at least 9 hours fasting using enzymatic assay procedure. RESULTS: Compared with daytime workers (58 subjects), shift workers (82 subjects) displayed higher TG/HDL-C ratio (r = 0.217, P = 0.013), higher serum TG levels (r = 0.220, P = 0.012), and lower HDL-C levels (r = -0.200, P = 0.016). Among shift workers, 30.5% were found to have a TG/HDL-C ratio >3.5 compared with 8.6% of daytime workers (P = 0.002). CONCLUSION: In the present study, shift work was shown to be associated with higher TG/HDL-C ratio, higher serum TG, and lower HDL-C levels. These findings might indicate that shift work is associated with increased insulin resistance and consequently higher risk of metabolic syndrome and cardiovascular diseases. PMID- 26357005 TI - ETV/Pea3 family transcription factor-encoding genes are overexpressed in CIC mutant oligodendrogliomas. AB - Oligodendrogliomas with combined loss of chromosome arms 1p and 19q are known to be particularly sensitive to chemotherapy, and the CIC gene located on 19q is known to be mutated in over 50% of the 1p/19q codeleted oligodendrogliomas. However, the role of CIC in the oligodendroglioma pathogenesis is not known. Exome sequencing of 11 oligodendroglial tumors identified 9 tumors with combined loss of 1p and 19q. Somatic mutations were found in the CIC and FUBP1 genes. Recurrent somatic mutations were also identified in the Notch signaling pathway genes NOTCH1 and MAML3, the chromatin modifying gene ARID1A and in KRAS. Comparison of the transcriptome profiles of CIC-mutant and CIC-wild type oligodendrogliomas from the study cohort as well as 65 1p/19q codeleted oligodendrogliomas from the TCGA cohort identified genes encoding the ETV transcription factor family to be significantly upregulated in the CIC-mutant tumors. Upregulation of a number of negative regulators of the receptor tyrosine kinase signaling pathway like Sprouty and SPRED family members in the CIC-mutant oligodendrogliomas is likely due to the constitutive activation of the pathway resulting from inactive CIC protein. Higher expression of the oncogenic ETV transcription factors in the CIC-mutant oligodendrogliomas may make these tumors more aggressive than the CIC-wild type tumors. PMID- 26357006 TI - Stent-in-stent, a safe and effective technique to remove fully embedded esophageal metal stents: case series and literature review. AB - BACKGROUND: Endoscopic stenting is a widely used method for managing esophageal anastomotic leaks and perforations. Self-expanding metal stents (SEMSs) have proved effective in sealing these defects, with a lower rate of displacement than that of self-expanding plastic stents (SEPSs) as a result of tissue proliferation and granulation tissue ingrowth at the uncovered portion of the stent, which anchor the prosthesis to the esophageal wall. Removal of a fully embedded stent is challenging because of the risk of bleeding and tears. MATERIALS AND METHODS: Temporary placement of a new stent within the first stent (stent-in-stent technique) may facilitate the mobilization and safe removal of both stents by inducing pressure ischemia of the granulation tissue. We report our own experience with the stent-in-stent technique in five consecutive patients in whom a partially covered Ultraflex stent had previously been implanted and compare our results with those in the current literature. RESULTS: The first SEMSs remained in place for a median of 40 days (range 18 - 68) without displacement. Placement of the new stent was technically successful in all patients. All stents were left in place for a median of 9 days. The overall stent-in-stent success rate was 100 % for the removal of embedded stents. No serious adverse events related to the procedure occurred. CONCLUSION: The procedure was safe, well tolerated, and effective. The use of a partially covered Ultraflex stent of the same size as the old stent for a limited time (<= 6 days) was consistently successful. PMID- 26357007 TI - Preparation and biomedical applications of programmable and multifunctional DNA nanoflowers. AB - We describe a comprehensive protocol for the preparation of multifunctional DNA nanostructures termed nanoflowers (NFs), which are self-assembled from long DNA building blocks generated via rolling-circle replication (RCR) of a designed template. NF assembly is driven by liquid crystallization and dense packaging of building blocks, which eliminates the need for conventional Watson-Crick base pairing. As a result of dense DNA packaging, NFs are resistant to nuclease degradation, denaturation or dissociation at extremely low concentrations. By manually changing the template sequence, many different functional moieties including aptamers, bioimaging agents and drug-loading sites could be easily integrated into NF particles, making NFs ideal candidates for a variety of applications in biomedicine. In this protocol, the preparation of multifunctional DNA NFs with highly tunable sizes is described for applications in cell targeting, intracellular imaging and drug delivery. Preparation and characterization of functional DNA NFs takes ~5 d; the following biomedical applications take ~10 d. PMID- 26357008 TI - Studying tumor growth in Drosophila using the tissue allograft method. AB - This protocol describes a method to allograft Drosophila larval tissue into adult fly hosts that can be used to assay the tumorigenic potential of mutant tissues. The tissue of interest is dissected, loaded into a fine glass needle and implanted into a host. Upon implantation, nontransformed tissues do not overgrow beyond their normal size, but malignant tumors grow without limit, are invasive and kill the host. By using this method, Drosophila malignant tumors can be transplanted repeatedly, for years, and therefore they can be aged beyond the short life span of flies. Because several hosts can be implanted using different pieces from a single tumor, the method also allows the tumor mass to be increased to facilitate further studies that may require large amounts of tissue (i.e., genomics, proteomics and so on). This method also provides an operational definition of hyperplastic, benign and malignant growth. The injection procedure itself requires only ~1 d. Tumor development can then be monitored until the death of the implanted hosts. PMID- 26357009 TI - Whole-mount immunolocalization to study female meiosis in Arabidopsis. AB - Here we describe a whole-mount immunolocalization protocol to follow the subcellular localization of proteins during female meiosis in Arabidopsis thaliana, a model species that is used to study sexual reproduction in flowering plants. By using confocal microscopy, the procedure allows one to follow megasporogenesis at all stages before differentiation of the functional megaspore. This in particular includes stages that occur during prophase I, such as the installation of the axial and central elements of the synaptonemal complex along the meiotic chromosomes. In contrast to procedures that require microtome sectioning or enzymatic isolation and smearing to separate female meiocytes from neighboring cells, this 3-day protocol preserves the constitution of the developing primordium and incorporates the architecture of the ovule to provide a temporal and spatial context to meiotic divisions. This opens up the possibility to systematically compare the dynamics of protein localization during female and male meiosis. Steps describe tissue collection and fixation, preparation of slides and polyacrylamide embedding, tissue permeabilization, antibody incubation, propidium iodide staining, and finally image acquisition by confocal microscopy. The procedure adds an essential technique to the toolkit of plant meiotic analysis, and it represents a framework for technical adaptations that could soon allow the analysis of plant reproductive alternatives to sexual reproduction. PMID- 26357011 TI - Ultrasonographic diaphragm thickness correlates with compound muscle action potential amplitude and forced vital capacity. AB - INTRODUCTION: Noninvasive evaluation of respiratory function in patients with various neuromuscular disorders is important for predicting life expectancy. METHODS: We performed B-mode ultrasonography (USG) and nerve conduction studies in 37 patients (16 had amyotrophic lateral sclerosis; 11, myopathy; and 10, neuropathy) and 10 controls. USG of the diaphragm was performed in the supine position using a linear probe over the intercostal space at the anterior axillary line. Diaphragm muscle thickness was measured at end-expiration. The amplitude of diaphragm compound muscle action potentials (CMAP) was obtained by phrenic nerve stimulation with a surface electrode. Respiratory function was measured with standard pulmonary function tests including forced vital capacity (FVC). RESULTS: Diaphragm thickness was significantly correlated with FVC (r = 0.74) and CMAP amplitude (r = 0.53). CONCLUSIONS: Diaphragm USG is useful for objective evaluation of pulmonary function in neuromuscular disorders without requiring undue patient effort or cooperation. PMID- 26357010 TI - Delivery of Adeno-Associated Virus Gene Therapy by Intravascular Limb Infusion Methods. AB - Recombinant adeno-associated virus (rAAV) can be delivered to the skeletal muscle of the limb (pelvic or thoracic) by means of regional intravascular delivery. This review summarizes the evolution of this technique to deliver rAAV either via the arterial blood supply or via the peripheral venous circulation. The focus of this review is on applications in large animal models, including preclinical studies. Based on this overview of past research, we aim to inform the design of preclinical and clinical studies. PMID- 26357012 TI - Effect of aflatoxin B1 on IgA+ cell number and immunoglobulin mRNA expression in the intestine of broilers. AB - Aflatoxin B1 (AFB1) is the most toxic group of mycotoxins produced by two species of the Aspergillus, common contaminants of food and animal feed. The purpose of our study was to determine the effect of AFB1 on the number of IgA(+) cell and immunoglobulin mRNA expression in the intestine of broilers. One hundred and fifty six one-day-old healthy Cobb broilers were randomly divided into the control group (the dosage of 0 mg/kg AFB1) and AFB1 group (the dosage of 0.6 mg/kg AFB1) with three replicates per group and 26 birds per replicate for 21 days, respectively. After necropsy at 7, 14 and 21 days of age, duodenum, jejunum and ileum samples were taken for analyzing IgA(+) cell by immunohistochemistry and IgA, pIgR, IgM and IgG mRNA expression by qRT-PCR. IgA(+) cells were mainly distributed in the lamina propria of small intestinal mucosa in both groups at 14 and 21 days of age. A significant decrease in the number of IgA(+) cells in the duodenum, jejunum and ileum was revealed in the AFB1 group compared with that of the control group. The expression levels of IgA, pIgR, IgM and IgG mRNA in the intestinal mucosa were lower in the AFB1 group than those in the control group at 14 and 21 days of age. Our data demonstrated that the dosage of 0.6 mg/kg AFB1 in broiler diet reduced the number of IgA(+) cell and the expression of IgA, pIgR, IgM and IgG mRNA in the small intestine. PMID- 26357013 TI - In Reply... Credat Emptor. PMID- 26357014 TI - Hormonal, Physiological, and Physical Performance During Simulated Kickboxing Combat: Differences Between Winners and Losers. AB - The aim of the current study was to investigate the hormonal, physiological, and physical responses of simulated kickboxing competition and evaluate if there was a difference between winners and losers. Twenty athletes of regional and national level participated in the study (mean +/- SD age 21.3 +/- 2.7 y, height 170.0 +/- 5.0 cm). Hormone (cortisol, testosterone, growth hormone), blood lactate [La], and glucose concentrations, as well as upper-body Wingate test and countermovement-jump (CMJ) performances, were measured before and after combats. Heart rate (HR) was measured throughout rounds 1, 2, and 3 and rating of perceived exertion (RPE) was taken after each round. All combats were recorded and analyzed to determine the length of different activity phases (high intensity, low-intensity, and referee pause) and the frequency of techniques. Hormones, glucose, [La], HR, and RPE increased (all P < .001) precombat to postcombat, while a decrease was observed for CMJ, Wingate test performance, body mass (all P < .001), and time of high-intensity activities (P = .005). There was no difference between winners and losers for hormonal, physiological, and physical variables (P > .05). However, winners executed more jab cross, total punches, roundhouse kicks, total kicks, and total attacking techniques (all P < .042) than losers. Kickboxing is an intermittent physically demanding sport that induces changes in the stress-related hormones soliciting the anaerobic lactic system. Training should be oriented to enhance kickboxers' anaerobic lactic fitness and their ability to strike at a sufficient rate. Further investigation is needed to identify possible differences in tactical and mental abilities that offer some insight into what makes winners winners. PMID- 26357015 TI - A balance of positive and negative regulators determines the pace of the segmentation clock. AB - Somitogenesis is regulated by a molecular oscillator that drives dynamic gene expression within the pre-somitic mesoderm. Previous mathematical models of the somitogenesis clock that invoke the mechanism of delayed negative feedback predict that its oscillation period depends on the sum of delays inherent to negative-feedback loops and inhibitor half-lives. We develop a mathematical model that explores the possibility that positive feedback also plays a role in determining the period of clock oscillations. The model predicts that increasing the half-life of the positive regulator, Notch intracellular domain (NICD), can lead to elevated NICD levels and an increase in the oscillation period. To test this hypothesis, we investigate a phenotype induced by various small molecule inhibitors in which the clock is slowed. We observe elevated levels and a prolonged half-life of NICD. Reducing NICD production rescues these effects. These data provide the first indication that tight control of the turnover of positive as well as negative regulators of the clock determines its periodicity. PMID- 26357017 TI - An Approach to Supporting Incremental Visual Data Classification. AB - Automatic data classification is a computationally intensive task that presents variable precision and is considerably sensitive to the classifier configuration and to data representation, particularly for evolving data sets. Some of these issues can best be handled by methods that support users' control over the classification steps. In this paper, we propose a visual data classification methodology that supports users in tasks related to categorization such as training set selection; model creation, application and verification; and classifier tuning. The approach is then well suited for incremental classification, present in many applications with evolving data sets. Data set visualization is accomplished by means of point placement strategies, and we exemplify the method through multidimensional projections and Neighbor Joining trees. The same methodology can be employed by a user who wishes to create his or her own ground truth (or perspective) from a previously unlabeled data set. We validate the methodology through its application to categorization scenarios of image and text data sets, involving the creation, application, verification, and adjustment of classification models. PMID- 26357018 TI - An Energy-Driven Motion Planning Method for Two Distant Postures. AB - In this paper, we present a local motion planning algorithm for character animation. We focus on motion planning between two distant postures where linear interpolation leads to penetrations. Our framework has two stages. The motion planning problem is first solved as a Boundary Value Problem (BVP) on an energy graph which encodes penetrations, motion smoothness and user control. Having established a mapping from the configuration space to the energy graph, a fast and robust local motion planning algorithm is introduced to solve the BVP to generate motions that could only previously be computed by global planning methods. In the second stage, a projection of the solution motion onto a constraint manifold is proposed for more user control. Our method can be integrated into current keyframing techniques. It also has potential applications in motion planning problems in robotics. PMID- 26357019 TI - Automated Aesthetic Analysis of Photographic Images. AB - We present a perceptually calibrated system for automatic aesthetic evaluation of photographic images. Our work builds upon the concepts of no-reference image quality assessment, with the main difference being our focus on rating image aesthetic attributes rather than detecting image distortions. In contrast to the recent attempts on the highly subjective aesthetic judgment problems such as binary aesthetic classification and the prediction of an image's overall aesthetics rating, our method aims on providing a reliable objective basis of comparison between aesthetic properties of different photographs. To that end our system computes perceptually calibrated ratings for a set of fundamental and meaningful aesthetic attributes, that together form an "aesthetic signature" of an image. We show that aesthetic signatures can still be used to improve upon the current state-of-the-art in automatic aesthetic judgment, but also enable interesting new photo editing applications such as automated aesthetic analysis, HDR tone mapping evaluation, and providing aesthetic feedback during multi-scale contrast manipulation. PMID- 26357016 TI - The GARP complex is required for cellular sphingolipid homeostasis. AB - Sphingolipids are abundant membrane components and important signaling molecules in eukaryotic cells. Their levels and localization are tightly regulated. However, the mechanisms underlying this regulation remain largely unknown. In this study, we identify the Golgi-associated retrograde protein (GARP) complex, which functions in endosome-to-Golgi retrograde vesicular transport, as a critical player in sphingolipid homeostasis. GARP deficiency leads to accumulation of sphingolipid synthesis intermediates, changes in sterol distribution, and lysosomal dysfunction. A GARP complex mutation analogous to a VPS53 allele causing progressive cerebello-cerebral atrophy type 2 (PCCA2) in humans exhibits similar, albeit weaker, phenotypes in yeast, providing mechanistic insights into disease pathogenesis. Inhibition of the first step of de novo sphingolipid synthesis is sufficient to mitigate many of the phenotypes of GARP-deficient yeast or mammalian cells. Together, these data show that GARP is essential for cellular sphingolipid homeostasis and suggest a therapeutic strategy for the treatment of PCCA2. PMID- 26357020 TI - Bi-Normal Filtering for Mesh Denoising. AB - Most mesh denoising techniques utilize only either the facet normal field or the vertex normal field of a mesh surface. The two normal fields, though contain some redundant geometry information of the same model, can provide additional information that the other field lacks. Thus, considering only one normal field is likely to overlook some geometric features. In this paper, we take advantage of the piecewise consistent property of the two normal fields and propose an effective framework in which they are filtered and integrated using a novel method to guide the denoising process. Our key observation is that, decomposing the inconsistent field at challenging regions into multiple piecewise consistent fields makes the two fields complementary to each other and produces better results. Our approach consists of three steps: vertex classification, bi-normal filtering, and vertex position update. The classification step allows us to filter the two fields on a piecewise smooth surface rather than a surface that is smooth everywhere. Based on the piecewise consistence of the two normal fields, we filtered them using a piecewise smooth region clustering strategy. To benefit from the bi-normal filtering, we design a quadratic optimization algorithm for vertex position update. Experimental results on synthetic and real data show that our algorithm achieves higher quality results than current approaches on surfaces with multifarious geometric features and irregular surface sampling. PMID- 26357021 TI - Geometrically Consistent Stereoscopic Image Editing Using Patch-Based Synthesis. AB - This paper presents a patch-based synthesis framework for stereoscopic image editing. The core of the proposed method builds upon a patch-based optimization framework with two key contributions: First, we introduce a depth-dependent patch pair similarity measure for distinguishing and better utilizing image contents with different depth structures. Second, a joint patch-pair search is proposed for properly handling the correlation between two views. The proposed method successfully overcomes two main challenges of editing stereoscopic 3D media: (1) maintaining the depth interpretation, and (2) providing controllability of the scene depth. The method offers patch-based solutions to a wide variety of stereoscopic image editing problems, including depth-guided texture synthesis, stereoscopic NPR, paint by depth, content adaptation, and 2D to 3D conversion. Several challenging cases are demonstrated to show the effectiveness of the proposed method. The results of user studies also show that the proposed method produces stereoscopic images with good stereoscopics and visual quality. PMID- 26357022 TI - Interpolation-Based Pathline Tracing in Particle-Based Flow Visualization. AB - Particle tracing in time-varying flow fields is traditionally performed by numerical integration of the underlying vector field. This procedure can become computationally expensive, especially in scattered, particle-based flow fields, which complicate interpolation due to the lack of an explicit neighborhood structure. If such a particle-based flow field allows for the identification of consecutive particle positions, an alternative approach to particle tracing can be employed: we substitute repeated numerical integration of vector data by geometric interpolation in the highly dynamic particle system as defined by the particle-based simulation. To allow for efficient and accurate location and interpolation of changing particle neighborhoods, we develop a modified k-d tree representation that is capable of creating a dynamic partitioning of even highly compressible data sets with strongly varying particle densities. With this representation we are able to efficiently perform pathline computation by identifying, tracking, and updating an enclosing, dynamic particle neighborhood as particles move overtime. We investigate and evaluate the complexity, accuracy, and robustness of this interpolation-based alternative approach to trajectory generation in compressible and incompressible particle systems generated by simulation techniques such as Smoothed Particle Hydrodynamics (SPH). PMID- 26357023 TI - Perception-Based Evaluation of Projection Methods for Multidimensional Data Visualization. AB - Similarity-based layouts generated by multidimensional projections or other dimension reduction techniques are commonly used to visualize high-dimensional data. Many projection techniques have been recently proposed addressing different objectives and application domains. Nonetheless, very little is known about the effectiveness of the generated layouts from a user's perspective, how distinct layouts from the same data compare regarding the typical visualization tasks they support, or how domain-specific issues affect the outcome of the techniques. Learning more about projection usage is an important step towards both consolidating their role in high-dimensional data analysis and taking informed decisions when choosing techniques. This work provides a contribution towards this goal. We describe the results of an investigation on the performance of layouts generated by projection techniques as perceived by their users. We conducted a controlled user study to test against the following hypotheses: (1) projection performance is task-dependent; (2) certain projections perform better on certain types of tasks; (3) projection performance depends on the nature of the data; and (4) subjects prefer projections with good segregation capability. We generated layouts of high-dimensional data with five techniques representative of different projection approaches. As application domains we investigated image and document data. We identified eight typical tasks, three of them related to segregation capability of the projection, three related to projection precision, and two related to incurred visual cluttering. Answers to questions were compared for correctness against 'ground truth' computed directly from the data. We also looked at subject confidence and task completion times. Statistical analysis of the collected data resulted in Hypotheses 1 and 3 being confirmed, Hypothesis 2 being confirmed partially and Hypotheses 4 could not be confirmed. We discuss our findings in comparison with some numerical measures of projection layout quality. Our results offer interesting insight on the use of projection layouts in data visualization tasks and provide a departing point for further systematic investigations. PMID- 26357024 TI - Planar Hexagonal Meshing for Architecture. AB - Mesh surfaces with planar hexagonal faces, what we refer to as PH meshes, offer an elegant way of paneling freeform architectural surfaces due to their node simplicity (i.e., valence-3 nodes) and naturally appealing layout. We investigate PH meshes to understand how the shape, size, and pattern of PH faces are constrained by surface geometry. This understanding enables us to develop an effective method for paneling freeform architectural surfaces with PH meshes. Our method first constructs an ideal triangulation of a given smooth surface, guided by surface geometry. We show that such an ideal triangulation leads to a Dupin regular PH mesh via tangent duality on the surface. We have developed several novel and effective techniques for improving undesirable mesh layouts caused by singular behaviors of surface curvature. We compute support structures associated with PH meshes, including exact vertex offsets and approximate edge offsets, as demanded in panel manufacturing. The efficacy of our method is validated by a number of architectural examples. PMID- 26357025 TI - SimpliFly: A Methodology for Simplification and Thematic Enhancement of Trajectories. AB - Movement data sets collected using today's advanced tracking devices consist of complex trajectories in terms of length, shape, and number of recorded positions. Multiple additional attributes characterizing the movement and its environment are often also included making the level of complexity even higher. Simplification of trajectories can improve the visibility of relevant information by reducing less relevant details while maintaining important movement patterns. We propose a systematic stepwise methodology for simplifying and thematically enhancing trajectories in order to support their visual analysis. The methodology is applied iteratively and is composed of: (a) a simplification step applied to reduce the morphological complexity of the trajectories, (b) a thematic enhancement step which aims at accentuating patterns of movement, and (c) the representation and interactive exploration of the results in order to make interpretations of the findings and further refinement to the simplification and enhancement process. We illustrate our methodology through an analysis example of two different types of tracks, aircraft and pedestrian movement. PMID- 26357026 TI - The Impact of Interactivity on Comprehending 2D and 3D Visualizations of Movement Data. AB - GPS, RFID, and other technologies have made it increasingly common to track the positions of people and objects over time as they move through two-dimensional spaces. Visualizing such spatio-temporal movement data is challenging because each person or object involves three variables (two spatial variables as a function of the time variable), and simply plotting the data on a 2D geographic map can result in overplotting and occlusion that hides details. This also makes it difficult to understand correlations between space and time. Software such as GeoTime can display such data with a three-dimensional visualization, where the 3rd dimension is used for time. This allows for the disambiguation of spatially overlapping trajectories, and in theory, should make the data clearer. However, previous experimental comparisons of 2D and 3D visualizations have so far found little advantage in 3D visualizations, possibly due to the increased complexity of navigating and understanding a 3D view. We present a new controlled experimental comparison of 2D and 3D visualizations, involving commonly performed tasks that have not been tested before, and find advantages in 3D visualizations for more complex tasks. In particular, we tease out the effects of various basic interactions and find that the 2D view relies significantly on "scrubbing" the timeline, whereas the 3D view relies mainly on 3D camera navigation. Our work helps to improve understanding of 2D and 3D visualizations of spatio-temporal data, particularly with respect to interactivity. PMID- 26357027 TI - Errata to "Tree Colors: Color Schemes for Tree-Structured Data". AB - Various revisions were made to the paper, "Tree colors: Color schemes for tree structured data," M. Tennekes and E. de Jonge, IEEE Trans. Vis. Comput. Graphics, vol. 20, no. 12, pp. 2072-2081, Dec. 2014. PMID- 26357028 TI - Exploring Brushlet Based 3D Textures in Transfer Function Specification for Direct Volume Rendering of Abdominal Organs. AB - Intuitive and differentiating domains for transfer function (TF) specification for direct volume rendering is an important research area for producing informative and useful 3D images. One of the emerging branches of this research is the texture based transfer functions. Although several studies in two, three, and four dimensional image processing show the importance of using texture information, these studies generally focus on segmentation. However, TFs can also be built effectively using appropriate texture information. To accomplish this, methods should be developed to collect wide variety of shape, orientation, and texture of biological tissues and organs. In this study, volumetric data (i.e., domain of a TF) is enhanced using brushlet expansion, which represents both low and high frequency textured structures at different quadrants in transform domain. Three methods (i.e., expert based manual, atlas and machine learning based automatic) are proposed for selection of the quadrants. Non-linear manipulation of the complex brushlet coefficients is also used prior to the tiling of selected quadrants and reconstruction of the volume. Applications to abdominal data sets acquired with CT, MR, and PET show that the proposed volume enhancement effectively improves the quality of 3D rendering using well-known TF specification techniques. PMID- 26357029 TI - Image-Based Reverse Engineering and Visual Prototyping of Woven Cloth. AB - Realistic visualization of cloth has many applications in computer graphics. An ongoing research problem is how to best represent and capture cloth models, specifically when considering computer aided design of cloth. Previous methods produce highly realistic images, however, they are either difficult to edit or require the measurement of large databases to capture all variations of a cloth sample. We propose a pipeline to reverse engineer cloth and estimate a parametrized cloth model from a single image. We introduce a geometric yarn model, integrating state-of-the-art textile research. We present an automatic analysis approach to estimate yarn paths, yarn widths, their variation and a weave pattern. Several examples demonstrate that we are able to model the appearance of the original cloth sample. Properties derived from the input image give a physically plausible basis that is fully editable using a few intuitive parameters. PMID- 26357030 TI - MegaMol--A Prototyping Framework for Particle-Based Visualization. AB - Visualization applications nowadays not only face increasingly larger datasets, but have to solve increasingly complex research questions. They often require more than a single algorithm and consequently a software solution will exceed the possibilities of simple research prototypes. Well-established systems intended for such complex visual analysis purposes have usually been designed for classical, mesh-based graphics approaches. For particle-based data, however, existing visualization frameworks are too generic - e.g. lacking possibilities for consistent low-level GPU optimization for high-performance graphics - and at the same time are too limited - e.g. by enforcing the use of structures suboptimal for some computations. Thus, we developed the system softwareMegaMol for visualization research on particle-based data. On the one hand, flexible data structures and functional module design allow for easy adaption to changing research questions, e.g. studying vapors in thermodynamics, solid material in physics, or complex functional macromolecules like proteins in biochemistry. Therefore, MegaMol is designed as a development framework. On the other hand, common functionality for data handling and advanced rendering implementations are available and beneficial for all applications. We present several case studies of work implemented using our system as well as a comparison to other freely available or open source systems. PMID- 26357031 TI - Munin: A Peer-to-Peer Middleware for Ubiquitous Analytics and Visualization Spaces. AB - We present Munin, a software framework for building ubiquitous analytics environments consisting of multiple input and output surfaces, such as tabletop displays, wall-mounted displays, and mobile devices. Munin utilizes a service based model where each device provides one or more dynamically loaded services for input, display, or computation. Using a peer-to-peer model for communication, it leverages IP multicast to replicate the shared state among the peers. Input is handled through a shared event channel that lets input and output devices be fully decoupled. It also provides a data-driven scene graph to delegate rendering to peers, thus creating a robust, fault-tolerant, decentralized system. In this paper, we describe Munin's general design and architecture, provide several examples of how we are using the framework for ubiquitous analytics and visualization, and present a case study on building a Munin assembly for multidimensional visualization. We also present performance results and anecdotal user feedback for the framework that suggests that combining a service-oriented, data-driven model with middleware support for data sharing and event handling eases the design and execution of high performance distributed visualizations. PMID- 26357032 TI - Parallel Style-Aware Image Cloning for Artworks. AB - We present style-aware image cloning, a novel image editing approach for artworks, which allows users to seamlessly insert any photorealistic or artificial objects into an artwork to create a new image that shares the same artistic style with the original artwork. To this end, a real-time image transfer algorithm is developed to stylize the cloned object according to a distance metric based on the artistic styles and semantic information. Several interactive functions, such as layering, shadowing, semantic labeling, and direction field editing, are provided to enhance the harmonization of the composite image. Extensive experimental results demonstrate the effectiveness of our method. PMID- 26357033 TI - Position-Dependent Importance Sampling of Light Field Luminaires. AB - The possibility to use real world light sources (aka luminaires) for synthesizing images greatly contributes to their physical realism. Among existing models, the ones based on light fields are attractive due to their ability to represent faithfully the near-field and due to their possibility of being directly acquired. In this paper, we introduce a dynamic sampling strategy for complex light field luminaires with the corresponding unbiased estimator. The sampling strategy is adapted, for each 3D scene position and each frame, by restricting the sampling domain dynamically and by balancing the number of samples between the different components of the representation. This is achieved efficiently by simple position-dependent affine transformations and restrictions of Cumulative Distributive Functions that ensure that every generated sample conveys energy and contributes to the final result. Therefore, our approach only requires a low number of samples to achieve almost converged results. We demonstrate the efficiency of our approach on modern hardware by introducing a GPU-based implementation. Combined with a fast shadow algorithm, our solution exhibits interactive frame rates for direct lighting for large measured luminaires. PMID- 26357034 TI - Progressive 3D Reconstruction of Planar-Faced Manifold Objects with DRF-Based Line Drawing Decomposition. AB - This paper presents an approach for reconstructing polyhedral objects from single view line drawings. Our approach separates a complex line drawing representing a manifold object into a series of simpler line drawings, based on the degree of reconstruction freedom (DRF). We then progressively reconstruct a complete 3D model from these simpler line drawings. Our experiments show that our decomposition algorithm is able to handle complex drawings which are challenging for the state of the art. The advantages of the presented progressive 3D reconstruction method over the existing reconstruction methods in terms of both robustness and efficiency are also demonstrated. PMID- 26357035 TI - Smooth Rotation Enhanced As-Rigid-As-Possible Mesh Animation. AB - In recent years, the As-Rigid-As-Possible (ARAP) shape deformation and shape interpolation techniques gained popularity, and the ARAP energy was successfully used in other applications as well. We improve the ARAP animation technique in two aspects. First, we introduce a new ARAP-type energy, named SR-ARAP, which has a consistent discretization for surfaces (triangle meshes). The quality of our new surface deformation scheme competes with the quality of the volumetric ARAP deformation (for tetrahedral meshes). Second, we propose a new ARAP shape interpolation method that is superior to prior art also based on the ARAP energy. This method is compatible with our new SR-ARAP energy, as well as with the ARAP volume energy. PMID- 26357036 TI - Space-Time Transfinite Interpolation of Volumetric Material Properties. AB - The paper presents a novel technique based on extension of a general mathematical method of transfinite interpolation to solve an actual problem in the context of a heterogeneous volume modelling area. It deals with time-dependent changes to the volumetric material properties (material density, colour, and others) as a transformation of the volumetric material distributions in space-time accompanying geometric shape transformations such as metamorphosis. The main idea is to represent the geometry of both objects by scalar fields with distance properties, to establish in a higher-dimensional space a time gap during which the geometric transformation takes place, and to use these scalar fields to apply the new space-time transfinite interpolation to volumetric material attributes within this time gap. The proposed solution is analytical in its nature, does not require heavy numerical computations and can be used in real-time applications. Applications of this technique also include texturing and displacement mapping of time-variant surfaces, and parametric design of volumetric microstructures. PMID- 26357037 TI - Visual Correlation Analysis of Numerical and Categorical Data on the Correlation Map. AB - Correlation analysis can reveal the complex relationships that often exist among the variables in multivariate data. However, as the number of variables grows, it can be difficult to gain a good understanding of the correlation landscape and important intricate relationships might be missed. We previously introduced a technique that arranged the variables into a 2D layout, encoding their pairwise correlations. We then used this layout as a network for the interactive ordering of axes in parallel coordinate displays. Our current work expresses the layout as a correlation map and employs it for visual correlation analysis. In contrast to matrix displays where correlations are indicated at intersections of rows and columns, our map conveys correlations by spatial proximity which is more direct and more focused on the variables in play. We make the following new contributions, some unique to our map: (1) we devise mechanisms that handle both categorical and numerical variables within a unified framework, (2) we achieve scalability for large numbers of variables via a multi-scale semantic zooming approach, (3) we provide interactive techniques for exploring the impact of value bracketing on correlations, and (4) we visualize data relations within the sub spaces spanned by correlated variables by projecting the data into a corresponding tessellation of the map. PMID- 26357038 TI - An Integrated Approach to Anti-Cancer Drug Sensitivity Prediction. AB - A framework for design of personalized cancer therapy requires the ability to predict the sensitivity of a tumor to anticancer drugs. The predictive modeling of tumor sensitivity to anti-cancer drugs has primarily focused on generating functions that map gene expressions and genetic mutation profiles to drug sensitivity. In this paper, we present a new approach for drug sensitivity prediction and combination therapy design based on integrated functional and genomic characterizations. The modeling approach when applied to data from the Cancer Cell Line Encyclopedia shows a significant gain in prediction accuracy as compared to elastic net and random forest techniques based on genomic characterizations. Utilizing a Mouse Embryonal Rhabdomyosarcoma cell culture and a drug screen of 60 targeted drugs, we show that predictive modeling based on functional data alone can also produce high accuracy predictions. The framework also allows us to generate personalized tumor proliferation circuits to gain further insights on the individualized biological pathway. PMID- 26357039 TI - Logistic Principal Component Analysis for Rare Variants in Gene-Environment Interaction Analysis. AB - The characteristics of low minor allele frequency (MAF) and weak individual effects make genome-wide association studies (GWAS) for rare variant single nucleotide polymorphisms (SNPs) more difficult when using conventional statistical methods. By aggregating the rare variant effects belonging to the same gene, collapsing is the most common way to enhance the detection of rare variant effects for association analyses with a given trait. In this paper, we propose a novel framework of MAF-based logistic principal component analysis (MLPCA) to derive aggregated statistics by explicitly modeling the correlation between rare variant SNP data, which is categorical. The derived aggregated statistics by MLPCA can then be tested as a surrogate variable in regression models to detect the gene-environment interaction from rare variants. In addition, MLPCA searches for the optimal linear combination from the best subset of rare variants according to MAF that has the maximum association with the given trait. We compared the power of our MLPCA-based methods with four existing collapsing methods in gene-environment interaction association analysis using both our simulation data set and Genetic Analysis Workshop 17 (GAW17) data. Our experimental results have demonstrated that MLPCA on two forms of genotype data representations achieves higher statistical power than those existing methods and can be further improved by introducing the appropriate sparsity penalty. The performance improvement by our MLPCA-based methods result from the derived aggregated statistics by explicitly modeling categorical SNP data and searching for the maximum associated subset of SNPs for collapsing, which helps better capture the combined effect from individual rare variants and the interaction with environmental factors. PMID- 26357040 TI - Network-Based Methods to Identify Highly Discriminating Subsets of Biomarkers. AB - Complex diseases such as various types of cancer and diabetes are conjectured to be triggered and influenced by a combination of genetic and environmental factors. To integrate potential effects from interplay among underlying candidate factors, we propose a new network-based framework to identify effective biomarkers by searching for groups of synergistic risk factors with high predictive power to disease outcome. An interaction network is constructed with node weights representing individual predictive power of candidate factors and edge weights capturing pairwise synergistic interactions among factors. We then formulate this network-based biomarker identification problem as a novel graph optimization model to search for multiple cliques with maximum overall weight, which we denote as the Maximum Weighted Multiple Clique Problem (MWMCP). To achieve optimal or near optimal solutions, both an analytical algorithm based on column generation method and a fast heuristic for large-scale networks have been derived. Our algorithms for MWMCP have been implemented to analyze two biomedical data sets: a Type 1 Diabetes (T1D) data set from the Diabetes Prevention Trial Type 1 (DPT-1) study, and a breast cancer genomics data set for metastasis prognosis. The results demonstrate that our network-based methods can identify important biomarkers with better prediction accuracy compared to the conventional feature selection that only considers individual effects. PMID- 26357041 TI - BM-SNP: A Bayesian Model for SNP Calling Using High Throughput Sequencing Data. AB - A single-nucleotide polymorphism (SNP) is a sole base change in the DNA sequence and is the most common polymorphism. Detection and annotation of SNPs are among the central topics in biomedical research as SNPs are believed to play important roles on the manifestation of phenotypic events, such as disease susceptibility. To take full advantage of the next-generation sequencing (NGS) technology, we propose a Bayesian approach, BM-SNP, to identify SNPs based on the posterior inference using NGS data. In particular, BM-SNP computes the posterior probability of nucleotide variation at each covered genomic position using the contents and frequency of the mapped short reads. The position with a high posterior probability of nucleotide variation is flagged as a potential SNP. We apply BM-SNP to two cell-line NGS data, and the results show a high ratio of overlap ( >95 percent) with the dbSNP database. Compared with MAQ, BM-SNP identifies more SNPs that are in dbSNP, with higher quality. The SNPs that are called only by BM-SNP but not in dbSNP may serve as new discoveries. The proposed BM-SNP method integrates information from multiple aspects of NGS data, and therefore achieves high detection power. BM-SNP is fast, capable of processing whole genome data at 20-fold average coverage in a short amount of time. PMID- 26357042 TI - Unfold High-Dimensional Clouds for Exhaustive Gating of Flow Cytometry Data. AB - Flow cytometry is able to measure the expressions of multiple proteins simultaneously at the single-cell level. A flow cytometry experiment on one biological sample provides measurements of several protein markers on or inside a large number of individual cells in that sample. Analysis of such data often aims to identify subpopulations of cells with distinct phenotypes. Currently, the most widely used analytical approach in the flow cytometry community is manual gating on a sequence of nested biaxial plots, which is highly subjective, labor intensive, and not exhaustive. To address those issues, a number of methods have been developed to automate the gating analysis by clustering algorithms. However, completely removing the subjectivity can be quite challenging. This paper describes an alternative approach. Instead of automating the analysis, we develop novel visualizations to facilitate manual gating. The proposed method views single-cell data of one biological sample as a high-dimensional point cloud of cells, derives the skeleton of the cloud, and unfolds the skeleton to generate 2D visualizations. We demonstrate the utility of the proposed visualization using real data, and provide quantitative comparison to visualizations generated from principal component analysis and multidimensional scaling. PMID- 26357043 TI - A Basic Protein Comparative Three-Dimensional Modeling Methodological Workflow Theory and Practice. AB - When working with proteins and studying its properties, it is crucial to have access to the three-dimensional structure of the molecule. If experimentally solved structures are not available, comparative modeling techniques can be used to generate useful protein models to subsidize structure-based research projects. In recent years, with Bioinformatics becoming the basis for the study of protein structures, there is a crescent need for the exposure of details about the algorithms behind the softwares and servers, as well as a need for protocols to guide in silico predictive experiments. In this article, we explore different steps of the comparative modeling technique, such as template identification, sequence alignment, generation of candidate structures and quality assessment, its peculiarities and theoretical description. We then present a practical step by-step workflow, to support the Biologist on the in silico generation of protein structures. Finally, we explore further steps on comparative modeling, presenting perspectives to the study of protein structures through Bioinformatics. We trust that this is a thorough guide for beginners that wish to work on the comparative modeling of proteins. PMID- 26357044 TI - A Parameter Estimation Method for Biological Systems modelled by ODE/DDE Models Using Spline Approximation and Differential Evolution Algorithm. AB - The inverse problem of identifying unknown parameters of known structure dynamical biological systems, which are modelled by ordinary differential equations or delay differential equations, from experimental data is treated in this paper. A two stage approach is adopted: first, combine spline theory and Nonlinear Programming (NLP), the parameter estimation problem is formulated as an optimization problem with only algebraic constraints; then, a new differential evolution (DE) algorithm is proposed to find a feasible solution. The approach is designed to handle problem of realistic size with noisy observation data. Three cases are studied to evaluate the performance of the proposed algorithm: two are based on benchmark models with priori-determined structure and parameters; the other one is a particular biological system with unknown model structure. In the last case, only a set of observation data available and in this case a nominal model is adopted for the identification. All the test systems were successfully identified by using a reasonable amount of experimental data within an acceptable computation time. Experimental evaluation reveals that the proposed method is capable of fast estimation on the unknown parameters with good precision. PMID- 26357045 TI - An Efficient and Very Accurate Method for Calculating Steady-State Sensitivities in Metabolic Reaction Systems. AB - Stability and sensitivity analyses of biological systems require the ad hocwriting of computer code, which is highly dependent on the particular model and burdensome for large systems. We propose a very accurate strategy to overcome this challenge. Its core concept is the conversion of the model into the format of biochemical systems theory (BST), which greatly facilitates the computation of sensitivities. First, the steady state of interest is determined by integrating the model equations toward the steady state and then using a Newton-Raphson method to fine-tune the result. The second step of conversion into the BST format requires several instances of numerical differentiation. The accuracy of this task is ensured by the use of a complex-variable Taylor scheme for all differentiation steps. The proposed strategy is implemented in a new software program, COSMOS, which automates the stability and sensitivity analysis of essentially arbitrary ODE models in a quick, yet highly accurate manner. The methods underlying the process are theoretically analyzed and illustrated with four representative examples: a simple metabolic reaction model; a model of aspartate-derived amino acid biosynthesis; a TCA-cycle model; and a modified TCA cycle model. COSMOS has been deposited to https://github.com/BioprocessdesignLab/COSMOS. PMID- 26357046 TI - Classifying Protein Sequences Using Regularized Multi-Task Learning. AB - Classification problems in which several learning tasks are organized hierarchically pose a special challenge because the hierarchical structure of the problems needs to be considered. Multi-task learning (MTL) provides a framework for dealing with such interrelated learning tasks. When two different hierarchical sources organize similar information, in principle, this combined knowledge can be exploited to further improve classification performance. We have studied this problem in the context of protein structure classification by integrating the learning process for two hierarchical protein structure classification database, SCOP and CATH. Our goal is to accurately predict whether a given protein belongs to a particular class in these hierarchies using only the amino acid sequences. We have utilized the recent developments in multi-task learning to solve the interrelated classification problems. We have also evaluated how the various relationships between tasks affect the classification performance. Our evaluations show that learning schemes in which both the classification databases are used outperform the schemes which utilize only one of them. PMID- 26357047 TI - Computing Elementary Flux Modes Involving a Set of Target Reactions. AB - Elementary flux mode (EM) computation is an important tool in the constraint based analysis of genome-scale metabolic networks. Due to the combinatorial complexity of these networks, as well as the advances in the level of detail to which they can be reconstructed, an exhaustive enumeration of all EMs is often not practical. Therefore, in recent years interest has shifted towards searching EMs with specific properties. We present a novel method that allows computing EMs containing a given set of target reactions. This generalizes previous algorithms where the set of target reactions consists of a single reaction. In the one reaction case, our method compares favorably to the previous approaches. In addition, we present several applications of our algorithm for computing EMs containing two target reactions in genome-scale metabolic networks. A software tool implementing the algorithms described in this paper is available at https://sourceforge.net/projects/caefm. PMID- 26357048 TI - Detection of Replication Origin Sites in Herpesvirus Genomes by Clustering and Scoring of Palindromes with Quadratic Entropy Measures. AB - Replication in herpesvirus genomes is a major concern of public health as they multiply rapidly during the lytic phase of infection that cause maximum damage to the host cells. Earlier research has established that sites of replication origin are dominated by high concentration of rare palindrome sequences of DNA. Computational methods are devised based on scoring to determine the concentration of palindromes. In this paper, we propose both extraction and localization of rare palindromes in an automated manner. Discrete Cosine Transform (DCT-II), a widely recognized image compression algorithm is utilized here to extract palindromic sequences based on their reverse complimentary symmetry property of existence. We formulate a novel approach to localize the rare palindrome clusters by devising a Minimum Quadratic Entropy (MQE) measure based on the Renyi's Quadratic Entropy (RQE) function. Experimental results over a large number of herpesvirus genomes show that the RQE based scoring of rare palindromes have higher order of sensitivity, and lesser false alarm in detecting concentration of rare palindromes and thereby sites of replication origin. PMID- 26357049 TI - Determining Semantically Related Significant Genes. AB - GO relation embodies some aspects of existence dependency. If GO term xis existence-dependent on GO term y, the presence of y implies the presence of x. Therefore, the genes annotated with the function of the GO term y are usually functionally and semantically related to the genes annotated with the function of the GO term x. A large number of gene set enrichment analysis methods have been developed in recent years for analyzing gene sets enrichment. However, most of these methods overlook the structural dependencies between GO terms in GO graph by not considering the concept of existence dependency. We propose in this paper a biological search engine called RSGSearch that identifies enriched sets of genes annotated with different functions using the concept of existence dependency. We observe that GO term xcannot be existence-dependent on GO term y, if x- and y- have the same specificity (biological characteristics). After encoding into a numeric format the contributions of GO terms annotating target genes to the semantics of their lowest common ancestors (LCAs), RSGSearch uses microarray experiment to identify the most significant LCA that annotates the result genes. We evaluated RSGSearch experimentally and compared it with five gene set enrichment systems. Results showed marked improvement. PMID- 26357050 TI - GECC: Gene Expression Based Ensemble Classification of Colon Samples. AB - Gene expression deviates from its normal composition in case a patient has cancer. This variation can be used as an effective tool to find cancer. In this study, we propose a novel gene expressions based colon classification scheme (GECC) that exploits the variations in gene expressions for classifying colon gene samples into normal and malignant classes. Novelty of GECC is in two complementary ways. First, to cater overwhelmingly larger size of gene based data sets, various feature extraction strategies, like, chi-square, F-Score, principal component analysis (PCA) and minimum redundancy and maximum relevancy (mRMR) have been employed, which select discriminative genes amongst a set of genes. Second, a majority voting based ensemble of support vector machine (SVM) has been proposed to classify the given gene based samples. Previously, individual SVM models have been used for colon classification, however, their performance is limited. In this research study, we propose an SVM-ensemble based new approach for gene based classification of colon, wherein the individual SVM models are constructed through the learning of different SVM kernels, like, linear, polynomial, radial basis function (RBF), and sigmoid. The predicted results of individual models are combined through majority voting. In this way, the combined decision space becomes more discriminative. The proposed technique has been tested on four colon, and several other binary-class gene expression data sets, and improved performance has been achieved compared to previously reported gene based colon cancer detection techniques. The computational time required for the training and testing of 208 * 5,851 data set has been 591.01 and 0.019 s, respectively. PMID- 26357051 TI - Gene Selection Using Locality Sensitive Laplacian Score. AB - Gene selection based on microarray data, is highly important for classifying tumors accurately. Existing gene selection schemes are mainly based on ranking statistics. From manifold learning standpoint, local geometrical structure is more essential to characterize features compared with global information. In this study, we propose a supervised gene selection method called locality sensitive Laplacian score (LSLS), which incorporates discriminative information into local geometrical structure, by minimizing local within-class information and maximizing local between-class information simultaneously. In addition, variance information is considered in our algorithm framework. Eventually, to find more superior gene subsets, which is significant for biomarker discovery, a two-stage feature selection method that combines the LSLS and wrapper method (sequential forward selection or sequential backward selection) is presented. Experimental results of six publicly available gene expression profile data sets demonstrate the effectiveness of the proposed approach compared with a number of state-of-the art gene selection methods. PMID- 26357052 TI - Identification of Functionally Related Enzymes by Learning-to-Rank Methods. AB - Enzyme sequences and structures are routinely used in the biological sciences as queries to search for functionally related enzymes in online databases. To this end, one usually departs from some notion of similarity, comparing two enzymes by looking for correspondences in their sequences, structures or surfaces. For a given query, the search operation results in a ranking of the enzymes in the database, from very similar to dissimilar enzymes, while information about the biological function of annotated database enzymes is ignored. In this work, we show that rankings of that kind can be substantially improved by applying kernel based learning algorithms. This approach enables the detection of statistical dependencies between similarities of the active cleft and the biological function of annotated enzymes. This is in contrast to search-based approaches, which do not take annotated training data into account. Similarity measures based on the active cleft are known to outperform sequence-based or structure-based measures under certain conditions. We consider the Enzyme Commission (EC) classification hierarchy for obtaining annotated enzymes during the training phase. The results of a set of sizeable experiments indicate a consistent and significant improvement for a set of similarity measures that exploit information about small cavities in the surface of enzymes. PMID- 26357053 TI - Identifying Non-Redundant Gene Markers from Microarray Data: A Multiobjective Variable Length PSO-Based Approach. AB - Identifying relevant genes which are responsible for various types of cancer is an important problem. In this context, important genes refer to the marker genes which change their expression level in correlation with the risk or progression of a disease, or with the susceptibility of the disease to a given treatment. Gene expression profiling by microarray technology has been successfully applied to classification and diagnostic prediction of cancers. However, extracting these marker genes from a huge set of genes contained by the microarray data set is a major problem. Most of the existing methods for identifying marker genes find a set of genes which may be redundant in nature. Motivated by this, a multiobjective optimization method has been proposed which can find a small set of non-redundant disease related genes providing high sensitivity and specificity simultaneously. In this article, the optimization problem has been modeled as a multiobjective one which is based on the framework of variable length particle swarm optimization. Using some real-life data sets, the performance of the proposed algorithm has been compared with that of other state-of-the-art techniques. PMID- 26357054 TI - Maximizing Protein Translation Rate in the Ribosome Flow Model: The Homogeneous Case. AB - Gene translation is the process in which intracellular macro-molecules, called ribosomes, decode genetic information in the mRNA chain into the corresponding proteins. Gene translation includes several steps. During the elongation step, ribosomes move along the mRNA in a sequential manner and link amino-acids together in the corresponding order to produce the proteins. The homogeneous ribosome flow model (HRFM) is a deterministic computational model for translation elongation under the assumption of constant elongation rates along the mRNA chain. The HRFM is described by a set of n first-order nonlinear ordinary differential equations, where n represents the number of sites along the mRNA chain. The HRFM also includes two positive parameters: ribosomal initiation rate and the (constant) elongation rate. In this paper, we show that the steady-state translation rate in the HRFM is a concave function of its parameters. This means that the problem of determining the parameter values that maximize the translation rate is relatively simple. Our results may contribute to a better understanding of the mechanisms and evolution of translation-elongation. We demonstrate this by using the theoretical results to estimate the initiation rate in M. musculus embryonic stem cell. The underlying assumption is that evolution optimized the translation mechanism. For the infinite-dimensional HRFM, we derive a closed-form solution to the problem of determining the initiation and transition rates that maximize the protein translation rate. We show that these expressions provide good approximations for the optimal values in the n dimensional HRFM already for relatively small values of n. These results may have applications for synthetic biology where an important problem is to re-engineer genomic systems in order to maximize the protein production rate. PMID- 26357055 TI - Molecular Modeling and Evaluation of Novel Dibenzopyrrole Derivatives as Telomerase Inhibitors and Potential Drug for Cancer Therapy. AB - During previous years, many studies on synthesis, as well as on anti-tumor, anti inflammatory and anti-bacterial activities of the pyrazole derivatives have been described. Certain pyrazole derivatives exhibit important pharmacological activities and have proved to be useful template in drug research. Considering importance of pyrazole template, in current work the series of novel inhibitors were designed by replacing central ring of acridine with pyrazole ring. These heterocyclic compounds were proposed as a new potential base for telomerase inhibitors. Obtained dibenzopyrrole structure was used as a novel scaffold structure and extension of inhibitors was done by different functional groups. Docking of newly designed compounds in the telomerase active site (telomerase catalytic subunit TERT) was carried out. All dibenzopyrrole derivatives were evaluated by three docking programs: CDOCKER, Ligandfit docking (Scoring Functions) and AutoDock. Compound C_9g, C_9k and C_9l performed best in comparison to all designed inhibitors during the docking in all methods and in interaction analysis. Introduction of pyrazole and extension of dibenzopyrrole in compounds confirm that such compound may act as potential telomerase inhibitors. PMID- 26357056 TI - Nonparametric Tikhonov Regularized NMF and Its Application in Cancer Clustering. AB - The Tikhonov regularized nonnegative matrix factorization (TNMF) is an NMF objective function that enforces smoothness on the computed solutions, and has been successfully applied to many problem domains including text mining, spectral data analysis, and cancer clustering. There is, however, an issue that is still insufficiently addressed in the development of TNMF algorithms, i.e., how to develop mechanisms that can learn the regularization parameters directly from the data sets. The common approach is to use fixed values based on a priori knowledge about the problem domains. However, from the linear inverse problems study it is known that the quality of the solutions of the Tikhonov regularized least square problems depends heavily on the choosing of appropriate regularization parameters. Since least squares are the building blocks of the NMF, it can be expected that similar situation also applies to the NMF. In this paper, we propose two formulas to automatically learn the regularization parameters from the data set based on the L-curve approach. We also develop a convergent algorithm for the TNMF based on the additive update rules. Finally, we demonstrate the use of the proposed algorithm in cancer clustering tasks. PMID- 26357057 TI - On Representing Protein Folding Patterns Using Non-Linear Parametric Curves. AB - Proteins fold into complex three-dimensional shapes. Simplified representations of their shapes are central to rationalise, compare, classify, and interpret protein structures. Traditional methods to abstract protein folding patterns rely on representing their standard secondary structural elements (helices and strands of sheet) using line segments. This results in ignoring a significant proportion of structural information. The motivation of this research is to derive mathematically rigorous and biologically meaningful abstractions of protein folding patterns that maximize the economy of structural description and minimize the loss of structural information. We report on a novel method to describe a protein as a non-overlapping set of parametric three dimensional curves of varying length and complexity. Our approach to this problem is supported by information theory and uses the statistical framework of minimum message length (MML) inference. We demonstrate the effectiveness of our non-linear abstraction to support efficient and effective comparison of protein folding patterns on a large scale. PMID- 26357058 TI - On the Number of Ranked Species Trees Producing Anomalous Ranked Gene Trees. AB - Analysis of probability distributions conditional on species trees has demonstrated the existence of anomalous ranked gene trees (ARGTs), ranked gene trees that are more probable than the ranked gene tree that accords with the ranked species tree. Here, to improve the characterization of ARGTs, we study enumerative and probabilistic properties of two classes of ranked labeled species trees, focusing on the presence or avoidance of certain subtree patterns associated with the production of ARGTs. We provide exact enumerations and asymptotic estimates for cardinalities of these sets of trees, showing that as the number of species increases without bound, the fraction of all ranked labeled species trees that are ARGT-producing approaches 1. This result extends beyond earlier existence results to provide a probabilistic claim about the frequency of ARGTs. PMID- 26357060 TI - ILP/SMT-Based Method for Design of Boolean Networks Based on Singleton Attractors. AB - Attractors in gene regulatory networks represent cell types or states of cells. In system biology and synthetic biology, it is important to generate gene regulatory networks with desired attractors. In this paper, we focus on a singleton attractor, which is also called a fixed point. Using a Boolean network (BN) model, we consider the problem of finding Boolean functions such that the system has desired singleton attractors and has no undesired singleton attractors. To solve this problem, we propose a matrix-based representation of BNs. Using this representation, the problem of finding Boolean functions can be rewritten as an Integer Linear Programming (ILP) problem and a Satisfiability Modulo Theories (SMT) problem. Furthermore, the effectiveness of the proposed method is shown by a numerical example on a WNT5A network, which is related to melanoma. The proposed method provides us a basic method for design of gene regulatory networks. PMID- 26357059 TI - Shifting-and-Scaling Correlation Based Biclustering Algorithm. AB - The existence of various types of correlations among the expressions of a group of biologically significant genes poses challenges in developing effective methods of gene expression data analysis. The initial focus of computational biologists was to work with only absolute and shifting correlations. However, researchers have found that the ability to handle shifting-and-scaling correlation enables them to extract more biologically relevant and interesting patterns from gene microarray data. In this paper, we introduce an effective shifting-and-scaling correlation measure named Shifting and Scaling Similarity (SSSim), which can detect highly correlated gene pairs in any gene expression data. We also introduce a technique named Intensive Correlation Search (ICS) biclustering algorithm, which uses SSSim to extract biologically significant biclusters from a gene expression data set. The technique performs satisfactorily with a number of benchmarked gene expression data sets when evaluated in terms of functional categories in Gene Ontology database. PMID- 26357061 TI - Improving Detection of Driver Genes: Power-Law Null Model of Copy Number Variation in Cancer. AB - In this paper, we study Copy Number Variation (CNV) data. The underlying process generating CNV segments is generally assumed to be memory-less, giving rise to an exponential distribution of segment lengths. In this paper, we provide evidence from cancer patient data, which suggests that this generative model is too simplistic, and that segment lengths follow a power-law distribution instead. We conjecture a simple preferential attachment generative model that provides the basis for the observed power-law distribution. We then show how an existing statistical method for detecting cancer driver genes can be improved by incorporating the power-law distribution in the null model. PMID- 26357062 TI - Organized Modularity in the Interactome: Evidence from the Analysis of Dynamic Organization in the Cell Cycle. AB - The organization of global protein interaction networks (PINs) has been extensively studied and heatedly debated. We revisited this issue in the context of the analysis of dynamic organization of a PIN in the yeast cell cycle. Statistically significant bimodality was observed when analyzing the distribution of the differences in expression peak between periodically expressed partners. A close look at their behavior revealed that date and party hubs derived from this analysis have some distinct features. There are no significant differences between them in terms of protein essentiality, expression correlation and semantic similarity derived from gene ontology (GO) biological process hierarchy. However, date hubs exhibit significantly greater values than party hubs in terms of semantic similarity derived from both GO molecular function and cellular component hierarchies. Relating to three-dimensional structures, we found that both single- and multi-interface proteins could become date hubs coordinating multiple functions performed at different times while party hubs are mainly multi interface proteins. Furthermore, we constructed and analyzed a PPI network specific to the human cell cycle and highlighted that the dynamic organization in human interactome is far more complex than the dichotomy of hubs observed in the yeast cell cycle. PMID- 26357063 TI - 2.5D Cartoon Hair Modeling and Manipulation. AB - This paper addresses a challenging single-view modeling and animation problem with cartoon images. Our goal is to model the hairs in a given cartoon image with consistent layering and occlusion, so that we can produce various visual effects from just a single image. We propose a novel 2.5D modeling approach to deal with this problem. Given an input image, we first segment the hairs of the cartoon character into regions of hair strands. Then, we apply our novel layering metric, which is derived from the Gestalt psychology, to automatically optimize the depth ordering among the hair strands. After that, we employ our hair completion method to fill the occluded part of each hair strand, and create a 2.5D model of the cartoon hair. By using this model, we can produce various visual effects, e.g., we develop a simplified fluid simulation model to produce wind blowing animations with the 2.5D hairs. To further demonstrate the applicability and versatility of our method, we compare our results with real cartoon hair animations, and also apply our model to produce a wide variety of hair manipulation effects, including hair editing and hair braiding. PMID- 26357064 TI - A Level-Set Method for Skinning Animated Particle Data. AB - In this paper, we present a straightforward, easy to implement method for particle skinning-generating surfaces from animated particle data. We cast the problem in terms of constrained optimization and solve the optimization using a level-set approach. The optimization seeks to minimize the thin-plate energy of the surface, while staying between surfaces defined by the union of spheres centered at the particles. Our approach skins each frame independently while preserving the temporal coherence of the underlying particle animation. Thus, it is well-suited for environments where particle skinning is treated as a post process, with each frame generated in parallel. Moreover, our approach is integrated with the OpenVDB library and the underlying partial differential equation is amenable to implicit time integration. We demonstrate our method on data generated by a variety of fluid simulation techniques and simple particle systems. PMID- 26357065 TI - Bas-Relief Generation and Shape Editing through Gradient-Based Mesh Deformation. AB - In this paper, we introduce a novel approach to bas-relief generation and shape editing that uses gradient-based mesh deformation as the theoretical foundation. Our approach differs from image-based methods in that it operates directly on the triangular mesh, and ensures that the mesh topology remains unchanged during geometric processing. By implicitly deforming the input mesh through gradient manipulation, our approach is applicable to both plane surface bas-relief generation and curved surface bas-relief generation. We propose a series of gradient-based algorithms, such as height field deformation, high slope optimization, fine detail preservation, curved surface flattening and relief mapping. Additionally, we present two types of shape editing tools that allow the user to interactively modify the bas-relief to exhibit a desired shape. Experimental results indicate that the proposed approach is effective in producing plausible and impressive bas-reliefs. PMID- 26357066 TI - Comparing Color and Leader Line Highlighting Strategies in Coordinated View Geovisualizations. AB - In most coordinated view geovisualization tools, a transient visual effect is used to highlight observations across views when brushed with a mouse or other input device. Most current geovisualization and information visualization systems use colored outlines or fills to highlight observations, but there remain a wide range of alternative visual strategies that can also be implemented and compared to color highlighting to evaluate user performance. This paper describes the results of an experiment designed to compare user performance with two highlighting methods; color and leader lines. Our study methodology uses eye tracking to capture participant eye fixations while they answer questions that require attention to highlighted observations in multiple views. Our results show that participants extract information as efficiently from coordinated view displays that use leader line highlighting to link information as they do from those that use a specific color to highlight items. We also found no significant differences when changing the color of the highlighting effect from red to black. We conclude that leader lines show significant potential for use as an alternative highlighting method in coordinated multiple view visualizations, allowing color to be reserved for representing thematic attributes of data. PMID- 26357067 TI - Distributed Seams for Gigapixel Panoramas. AB - Gigapixel panoramas are an increasingly popular digital image application. They are often created as a mosaic of many smaller images. The mosaic acquisition can take many hours causing the individual images to differ in exposure and lighting conditions. A blending operation is often necessary to give the appearance of a seamless image. The blending quality depends on the magnitude of discontinuity along the image boundaries. Often, new boundaries, or seams, are first computed that minimize this transition. Current techniques based on multi-labeling Graph Cuts are too slow and memory intensive for gigapixel sized panoramas. In this paper, we present a parallel, out-of-core seam computing technique that is fast, has small memory footprint, and is capable of running efficiently on different types of parallel systems. Its maximum memory usage is configurable, in the form of a cache, which can improve performance by reducing redundant disk I/O and computations. It shows near-perfect scaling on symmetric multiprocessing systems and good scaling on clusters and distributed shared memory systems. Our technique improves the time required to compute seams for gigapixel imagery from many hours (or even days) to just a few minutes, while still producing boundaries with energy that is on-par with Graph Cuts. PMID- 26357068 TI - Dual-Matrix Sampling for Scalable Translucent Material Rendering. AB - This paper introduces a scalable algorithm for rendering translucent materials with complex lighting. We represent the light transport with a diffusion approximation by a dual-matrix representation with the Light-to-Surface and Surface-to-Camera matrices. By exploiting the structures within the matrices, the proposed method can locate surface samples with little contribution by using only subsampled matrices and avoid wasting computation on these samples. The decoupled estimation of irradiance and diffuse BSSRDFs also allows us to have a tight error bound, making the adaptive diffusion approximation more efficient and accurate. Experiments show that our method outperforms previous methods for translucent material rendering, especially in large scenes with massive translucent surfaces shaded by complex illumination. PMID- 26357069 TI - Foldover-Free Mesh Warping for Constrained Texture Mapping. AB - Mapping texture onto 3D meshes with positional constraints is a popular technique that can effectively enhance the visual realism of geometric models. Such a process usually requires constructing a valid mesh embedding satisfying a set of positional constraints, which is known to be a challenging problem. This paper presents a novel algorithm for computing a foldover-free piecewise linear mapping with exact positional constraints. The algorithm begins with an unconstrained planar embedding, followed by iterative constrained mesh transformations. At the heart of the algorithm are radial basis function (RBF)-based warping and the longest edge bisection (LEB)-based refinement. A delicate integration of the RBF based warping and the LEB-based refinement provides a provably-foldover-free, smooth constrained mesh warping, which can handle a large number of constraints and output a visually pleasing mapping result without extra smoothing optimization. The experiments demonstrate the effectiveness of the proposed algorithm. PMID- 26357070 TI - HART: A Hybrid Architecture for Ray Tracing Animated Scenes. AB - We present a hybrid architecture, inspired by asynchronous BVH construction [1], for ray tracing animated scenes. Our hybrid architecture utilizes heterogeneous hardware resources: dedicated ray-tracing hardware for BVH updates and ray traversal and a CPU for BVH reconstruction. We also present a traversal scheme using a primitive's axis-aligned bounding box (PrimAABB). This scheme reduces ray primitive intersection tests by reusing existing BVH traversal units and the primAABB data for tree updates; it enables the use of shallow trees to reduce tree build times, tree sizes, and bus bandwidth requirements. Furthermore, we present a cache scheme that exploits consecutive memory access by reusing data in an L1 cache block. We perform cycle-accurate simulations to verify our architecture, and the simulation results indicate that the proposed architecture can achieve real-time Whitted ray tracing animated scenes at 1,920 * 1,200 resolution. This result comes from our high-performance hardware architecture and minimized resource requirements for tree updates. PMID- 26357071 TI - VectorLens: Angular Selection of Curves within 2D Dense Visualizations. AB - We investigate the selection of curves within a 2D visualization by specifying their angle or slope. Such angular selection has applications in parallel coordinates, time series visualizations, spatio-temporal movement data, etc. Our interaction technique specifies a region of interest in the visualization (with a position and diameter), a direction, and an angular tolerance, all with a single drag. We experimentally compared this angular selection technique with other techniques for selecting curves, and found that angular selection resulted in a higher number of trials that were successful on the first attempt and fewer incorrectly selected curves, and was also subjectively preferred by participants. We then present the design of a popup lens widget, called the VectorLens, that allows for easy angular selection and also allows the user to perform additional filtering operations based on type of curve. Multiple VectorLens widgets can also be instantiated to combine the results of their filtering operations with boolean operators. PMID- 26357072 TI - A Topologically-Informed Hyperstreamline Seeding Method for Alignment Tensor Fields. AB - A topologically-informed hyperstreamline seeding method is presented for visualization of alignment tensor fields. The method is inspired by and applied to visualization of nematic liquid crystal (LC) orientation dynamics simulations. The method distributes hyperstreamlines along domain boundaries and edges of a nearest-neighbor graph whose vertices are degenerate regions of the alignment tensor field, which correspond to orientational defects in a nematic LC domain. This is accomplished without iteration while conforming to a user-specified spacing between hyperstreamlines and avoids possible failure modes associated with hyperstreamline integration in the vicinity of degeneracies in alignment (orientational defects). It is shown that the presented seeding method enables automated hyperstreamline-based visualization of a broad range of alignment tensor fields which enhances the ability of researchers to interpret these fields and provides an alternative to using glyph-based techniques. PMID- 26357073 TI - Personal Visualization and Personal Visual Analytics. AB - Data surrounds each and every one of us in our daily lives, ranging from exercise logs, to archives of our interactions with others on social media, to online resources pertaining to our hobbies. There is enormous potential for us to use these data to understand ourselves better and make positive changes in our lives. Visualization (Vis) and visual analytics (VA) offer substantial opportunities to help individuals gain insights about themselves, their communities and their interests; however, designing tools to support data analysis in non-professional life brings a unique set of research and design challenges. We investigate the requirements and research directions required to take full advantage of Vis and VA in a personal context. We develop a taxonomy of design dimensions to provide a coherent vocabulary for discussing personal visualization and personal visual analytics. By identifying and exploring clusters in the design space, we discuss challenges and share perspectives on future research. This work brings together research that was previously scattered across disciplines. Our goal is to call research attention to this space and engage researchers to explore the enabling techniques and technology that will support people to better understand data relevant to their personal lives, interests, and needs. PMID- 26357074 TI - MRFy: Remote Homology Detection for Beta-Structural Proteins Using Markov Random Fields and Stochastic Search. AB - We introduce MRFy, a tool for protein remote homology detection that captures beta-strand dependencies in the Markov random field. Over a set of 11 SCOP beta structural superfamilies, MRFy shows a 14 percent improvement in mean Area Under the Curve for the motif recognition problem as compared to HMMER, 25 percent improvement as compared to RAPTOR, 14 percent improvement as compared to HHPred, and a 18 percent improvement as compared to CNFPred and RaptorX. MRFy was implemented in the Haskell functional programming language, and parallelizes well on multi-core systems. MRFy is available, as source code as well as an executable, from http://mrfy.cs.tufts.edu/. PMID- 26357075 TI - RLIMS-P 2.0: A Generalizable Rule-Based Information Extraction System for Literature Mining of Protein Phosphorylation Information. AB - We introduce RLIMS-P version 2.0, an enhanced rule-based information extraction (IE) system for mining kinase, substrate, and phosphorylation site information from scientific literature. Consisting of natural language processing and IE modules, the system has integrated several new features, including the capability of processing full-text articles and generalizability towards different post translational modifications (PTMs). To evaluate the system, sets of abstracts and full-text articles, containing a variety of textual expressions, were annotated. On the abstract corpus, the system achieved F-scores of 0.91, 0.92, and 0.95 for kinases, substrates, and sites, respectively. The corresponding scores on the full-text corpus were 0.88, 0.91, and 0.92. It was additionally evaluated on the corpus of the 2013 BioNLP-ST GE task, and achieved an F-score of 0.87 for the phosphorylation core task, improving upon the results previously reported on the corpus. Full-scale processing of all abstracts in MEDLINE and all articles in PubMed Central Open Access Subset has demonstrated scalability for mining rich information in literature, enabling its adoption for biocuration and for knowledge discovery. The new system is generalizable and it will be adapted to tackle other major PTM types. RLIMS-P 2.0 online system is available online (http://proteininformationresource.org/rlimsp/) and the developed corpora are available from iProLINK (http://proteininformationresource.org/iprolink/). PMID- 26357077 TI - Global Network Alignment in the Context of Aging. AB - Analogous to sequence alignment, network alignment (NA) can be used to transfer biological knowledge across species between conserved network regions. NA faces two algorithmic challenges: 1) Which cost function to use to capture "similarities" between nodes in different networks? 2) Which alignment strategy to use to rapidly identify "high-scoring" alignments from all possible alignments? We "break down" existing state-of-the-art methods that use both different cost functions and different alignment strategies to evaluate each combination of their cost functions and alignment strategies. We find that a combination of the cost function of one method and the alignment strategy of another method beats the existing methods. Hence, we propose this combination as a novel superior NA method. Then, since human aging is hard to study experimentally due to long lifespan, we use NA to transfer aging-related knowledge from well annotated model species to poorly annotated human. By doing so, we produce novel human aging-related knowledge, which complements currently available knowledge about aging that has been obtained mainly by sequence alignment. We demonstrate significant similarity between topological and functional properties of our novel predictions and those of known aging-related genes. We are the first to use NA to learn more about aging. PMID- 26357076 TI - Phenotype-Dependent Coexpression Gene Clusters: Application to Normal and Premature Ageing. AB - Hutchinson Gilford progeria syndrome (HGPS) is a rare genetic disease with symptoms of aging at a very early age. Its molecular basis is not entirely clear, although profound gene expression changes have been reported, and there are some known and other presumed overlaps with normal aging process. Identification of genes with agingor HGPS-associated expression changes is thus an important problem. However, standard regression approaches are currently unsuitable for this task due to limited sample sizes, thus motivating development of alternative approaches. Here, we report a novel iterative multiple regression approach that leverages co-expressed gene clusters to identify gene clusters whose expression co-varies with age and/or HGPS. We have applied our approach to novel RNA-seq profiles in fibroblast cell cultures at three different cellular ages, both from HGPS patients and normal samples. After establishing the robustness of our approach, we perform a comparative investigation of biological processes underlying normal aging and HGPS. Our results recapitulate previously known processes underlying aging as well as suggest numerous unique processes underlying aging and HGPS. The approach could also be useful in detecting phenotype-dependent co-expression gene clusters in other contexts with limited sample sizes. PMID- 26357078 TI - Reachability Analysis in Probabilistic Biological Networks. AB - Extra-cellular molecules trigger a response inside the cell by initiating a signal at special membrane receptors (i.e., sources), which is then transmitted to reporters (i.e., targets) through various chains of interactions among proteins. Understanding whether such a signal can reach from membrane receptors to reporters is essential in studying the cell response to extra-cellular events. This problem is drastically complicated due to the unreliability of the interaction data. In this paper, we develop a novel method, called PReach (Probabilistic Reachability), that precisely computes the probability that a signal can reach from a given collection of receptors to a given collection of reporters when the underlying signaling network is uncertain. This is a very difficult computational problem with no known polynomial-time solution. PReach represents each uncertain interaction as a bi-variate polynomial. It transforms the reachability problem to a polynomial multiplication problem. We introduce novel polynomial collapsing operators that associate polynomial terms with possible paths between sources and targets as well as the cuts that separate sources from targets. These operators significantly shrink the number of polynomial terms and thus the running time. PReach has much better time complexity than the recent solutions for this problem. Our experimental results on real data sets demonstrate that this improvement leads to orders of magnitude of reduction in the running time over the most recent methods. Availability: All the data sets used, the software implemented and the alignments found in this paper are available at http://bioinformatics.cise.ufl.edu/PReach/. PMID- 26357079 TI - GLProbs: Aligning Multiple Sequences Adaptively. AB - This paper introduces a simple and effective approach to improve the accuracy of multiple sequence alignment. We use a natural measure to estimate the similarity of the input sequences, and based on this measure, we align the input sequences differently. For example, for inputs with high similarity, we consider the whole sequences and align them globally, while for those with moderately low similarity, we may ignore the flank regions and align them locally. To test the effectiveness of this approach, we have implemented a multiple sequence alignment tool called GLProbs and compared its performance with about one dozen leading alignment tools on three benchmark alignment databases, and GLProbs's alignments have the best scores in almost all testings. We have also evaluated the practicability of the alignments of GLProbs by applying the tool to three biological applications, namely phylogenetic trees construction, protein secondary structure prediction and the detection of high risk members for cervical cancer in the HPV-E6 family, and the results are very encouraging. PMID- 26357080 TI - Prediction and Informative Risk Factor Selection of Bone Diseases. AB - With the booming of healthcare industry and the overwhelming amount of electronic health records (EHRs) shared by healthcare institutions and practitioners, we take advantage of EHR data to develop an effective disease risk management model that not only models the progression of the disease, but also predicts the risk of the disease for early disease control or prevention. Existing models for answering these questions usually fall into two categories: the expert knowledge based model or the handcrafted feature set based model. To fully utilize the whole EHR data, we will build a framework to construct an integrated representation of features from all available risk factors in the EHR data and use these integrated features to effectively predict osteoporosis and bone fractures. We will also develop a framework for informative risk factor selection of bone diseases. A pair of models for two contrast cohorts (e.g., diseased patients versus non-diseased patients) will be established to discriminate their characteristics and find the most informative risk factors. Several empirical results on a real bone disease data set show that the proposed framework can successfully predict bone diseases and select informative risk factors that are beneficial and useful to guide clinical decisions. PMID- 26357081 TI - Capturing Uncertainty by Modeling Local Transposon Insertion Frequencies Improves Discrimination of Essential Genes. AB - Transposon mutagenesis experiments enable the identification of essential genes in bacteria. Deep-sequencing of mutant libraries provides a large amount of high resolution data on essentiality. Statistical methods developed to analyze this data have traditionally assumed that the probability of observing a transposon insertion is the same across the genome. This assumption, however, is inconsistent with the observed insertion frequencies from transposon mutant libraries of M. tuberculosis. We propose a modified Binomial model of essentiality that can characterize the insertion probability of individual genes in which we allow local variation in the background insertion frequency in different non-essential regions of the genome. Using the Metropolis-Hastings algorithm, samples of the posterior insertion probabilities were obtained for each gene, and the probability of each gene being essential is estimated. We compared our predictions to those of previous methods and show that, by taking into consideration local insertion frequencies, our method is capable of making more conservative predictions that better match what is experimentally known about essential and non-essential genes. PMID- 26357082 TI - A Hierarchical Clustering Method of Selecting Kernel SNP to Unify Informative SNP and Tag SNP. AB - Various strategies can be used to select representative single nucleotide polymorphisms (SNPs) from a large number of SNPs, such as tag SNP for haplotype coverage and informative SNP for haplotype reconstruction, respectively. Representative SNPs are not only instrumental in reducing the cost of genotyping, but also serve an important function in narrowing the combinatorial space in epistasis analysis. The capacity of kernel SNPs to unify informative SNP and tag SNP is explored, and inconsistencies are minimized in further studies. The correlation between multiple SNPs is formalized using multi-information measures. In extending the correlation, a distance formula for measuring the similarity between clusters is first designed to conduct hierarchical clustering. Hierarchical clustering consists of both information gain and haplotype diversity, so that the proposed approach can achieve unification. The kernel SNPs are then selected from every cluster through the top rank or backward elimination scheme. Using these kernel SNPs, extensive experimental comparisons are conducted between informative SNPs on haplotype reconstruction accuracy and tag SNPs on haplotype coverage. Results indicate that the kernel SNP can practically unify informative SNP and tag SNP and is therefore adaptable to various applications. PMID- 26357083 TI - A Maximum A Posteriori Probability and Time-Varying Approach for Inferring Gene Regulatory Networks from Time Course Gene Microarray Data. AB - Unlike most conventional techniques with static model assumption, this paper aims to estimate the time-varying model parameters and identify significant genes involved at different timepoints from time course gene microarray data. We first formulate the parameter identification problem as a new maximum a posteriori probability estimation problem so that prior information can be incorporated as regularization terms to reduce the large estimation variance of the high dimensional estimation problem. Under this framework, sparsity and temporal consistency of the model parameters are imposed using L1-regularization and novel continuity constraints, respectively. The resulting problem is solved using the L BFGS method with the initial guess obtained from the partial least squares method. A novel forward validation measure is also proposed for the selection of regularization parameters, based on both forward and current prediction errors. The proposed method is evaluated using a synthetic benchmark testing data and a publicly available yeast Saccharomyces cerevisiae cell cycle microarray data. For the latter particularly, a number of significant genes identified at different timepoints are found to be biological significant according to previous findings in biological experiments. These suggest that the proposed approach may serve as a valuable tool for inferring time-varying gene regulatory networks in biological studies. PMID- 26357084 TI - An Algorithm for Motif Discovery with Iteration on Lengths of Motifs. AB - Analysis of DNA sequence motifs is becoming increasingly important in the study of gene regulation, and the identification of motif in DNA sequences is a complex problem in computational biology. Motif discovery has attracted the attention of more and more researchers, and varieties of algorithms have been proposed. Most existing motif discovery algorithms fix the motif's length as one of the input parameters. In this paper, a novel method is proposed to identify the optimal length of the motif and the optimal motif with that length, through an iteration process on increasing length numbers. For each fixed length, a modified genetic algorithm (GA) is used for finding the optimal motif with that length. Three operators are used in the modified GA: Mutation that is similar to the one used in usual GA but is modified to avoid local optimum in our case, and Addition and Deletion that are proposed by us for the problem. A criterion is given for singling out the optimal length in the increasing motif's lengths. We call this method AMDILM (an algorithm for motif discovery with iteration on lengths of motifs). The experiments on simulated data and real biological data show that AMDILM can accurately identify the optimal motif length. Meanwhile, the optimal motifs discovered by AMDILM are consistent with the real ones and are similar with the motifs obtained by the three well-known methods: Gibbs Sampler, MEME and Weeder. PMID- 26357085 TI - Discovering Binding Cores in Protein-DNA Binding Using Association Rule Mining with Statistical Measures. AB - Understanding binding cores is of fundamental importance in deciphering Protein DNA (TF-TFBS) binding and for the deep understanding of gene regulation. Traditionally, binding cores are identified in resolved high-resolution 3D structures. However, it is expensive, labor-intensive and time-consuming to obtain these structures. Hence, it is promising to discover binding cores computationally on a large scale. Previous studies successfully applied association rule mining to discover binding cores from TF-TFBS binding sequence data only. Despite the successful results, there are limitations such as the use of tight support and confidence thresholds, the distortion by statistical bias in counting pattern occurrences, and the lack of a unified scheme to rank TF-TFBS associated patterns. In this study, we proposed an association rule mining algorithm incorporating statistical measures and ranking to address these limitations. Experimental results demonstrated that, even when the threshold on support was lowered to one-tenth of the value used in previous studies, a satisfactory verification ratio was consistently observed under different confidence levels. Moreover, we proposed a novel ranking scheme for TF-TFBS associated patterns based on p-values and co-support values. By comparing with other discovery approaches, the effectiveness of our algorithm was demonstrated. Eighty-four binding cores with PDB support are uniquely identified. PMID- 26357086 TI - Gene Tree Diameter for Deep Coalescence. AB - The deep coalescence cost accounts for discord caused by deep coalescence between a gene tree and a species tree. It is a major concern that the diameter of a gene tree (the tree's maximum deep coalescence cost across all species trees) depends on its topology, which can largely obfuscate phylogenetic studies. While this bias can be compensated by normalizing the deep coalescence cost using diameters, obtaining them efficiently has been posed as an open problem by Than and Rosenberg. Here, we resolve this problem by describing a linear time algorithm to compute the diameter of a gene tree. In addition, we provide a complete classification of the species trees yielding this diameter to guide phylogenetic analyses. PMID- 26357087 TI - Heterogeneous Cloud Framework for Big Data Genome Sequencing. AB - The next generation genome sequencing problem with short (long) reads is an emerging field in numerous scientific and big data research domains. However, data sizes and ease of access for scientific researchers are growing and most current methodologies rely on one acceleration approach and so cannot meet the requirements imposed by explosive data scales and complexities. In this paper, we propose a novel FPGA-based acceleration solution with MapReduce framework on multiple hardware accelerators. The combination of hardware acceleration and MapReduce execution flow could greatly accelerate the task of aligning short length reads to a known reference genome. To evaluate the performance and other metrics, we conducted a theoretical speedup analysis on a MapReduce programming platform, which demonstrates that our proposed architecture have efficient potential to improve the speedup for large scale genome sequencing applications. Also, as a practical study, we have built a hardware prototype on the real Xilinx FPGA chip. Significant metrics on speedup, sensitivity, mapping quality, error rate, and hardware cost are evaluated, respectively. Experimental results demonstrate that the proposed platform could efficiently accelerate the next generation sequencing problem with satisfactory accuracy and acceptable hardware cost. PMID- 26357088 TI - Identification of Protein Complexes Using Weighted PageRank-Nibble Algorithm and Core-Attachment Structure. AB - Protein complexes play a significant role in understanding the underlying mechanism of most cellular functions. Recently, many researchers have explored computational methods to identify protein complexes from protein-protein interaction (PPI) networks. One group of researchers focus on detecting local dense subgraphs which correspond to protein complexes by considering local neighbors. The drawback of this kind of approach is that the global information of the networks is ignored. Some methods such as Markov Clustering algorithm (MCL), PageRank-Nibble are proposed to find protein complexes based on random walk technique which can exploit the global structure of networks. However, these methods ignore the inherent core-attachment structure of protein complexes and treat adjacent node equally. In this paper, we design a weighted PageRank-Nibble algorithm which assigns each adjacent node with different probability, and propose a novel method named WPNCA to detect protein complex from PPI networks by using weighted PageRank-Nibble algorithm and core-attachment structure. Firstly, WPNCA partitions the PPI networks into multiple dense clusters by using weighted PageRank-Nibble algorithm. Then the cores of these clusters are detected and the rest of proteins in the clusters will be selected as attachments to form the final predicted protein complexes. The experiments on yeast data show that WPNCA outperforms the existing methods in terms of both accuracy and p-value. The software for WPNCA is available at "http://netlab.csu.edu.cn/bioinfomatics/weipeng/WPNCA/download.html". PMID- 26357089 TI - Identifying Affinity Classes of Inorganic Materials Binding Sequences via a Graph Based Model. AB - Rapid advances in bionanotechnology have recently generated growing interest in identifying peptides that bind to inorganic materials and classifying them based on their inorganic material affinities. However, there are some distinct characteristics of inorganic materials binding sequence data that limit the performance of many widely-used classification methods when applied to this problem. In this paper, we propose a novel framework to predict the affinity classes of peptide sequences with respect to an associated inorganic material. We first generate a large set of simulated peptide sequences based on an amino acid transition matrix tailored for the specific inorganic material. Then the probability of test sequences belonging to a specific affinity class is calculated by minimizing an objective function. In addition, the objective function is minimized through iterative propagation of probability estimates among sequences and sequence clusters. Results of computational experiments on two real inorganic material binding sequence data sets show that the proposed framework is highly effective for identifying the affinity classes of inorganic material binding sequences. Moreover, the experiments on the structural classification of proteins (SCOP) data set shows that the proposed framework is general and can be applied to traditional protein sequences. PMID- 26357090 TI - Parallel Implementation of MAFFT on CUDA-Enabled Graphics Hardware. AB - Multiple sequence alignment (MSA) constitutes an extremely powerful tool for many biological applications including phylogenetic tree estimation, secondary structure prediction, and critical residue identification. However, aligning large biological sequences with popular tools such as MAFFT requires long runtimes on sequential architectures. Due to the ever increasing sizes of sequence databases, there is increasing demand to accelerate this task. In this paper, we demonstrate how graphic processing units (GPUs), powered by the compute unified device architecture (CUDA), can be used as an efficient computational platform to accelerate the MAFFT algorithm. To fully exploit the GPU's capabilities for accelerating MAFFT, we have optimized the sequence data organization to eliminate the bandwidth bottleneck of memory access, designed a memory allocation and reuse strategy to make full use of limited memory of GPUs, proposed a new modified-run-length encoding (MRLE) scheme to reduce memory consumption, and used high-performance shared memory to speed up I/O operations. Our implementation tested in three NVIDIA GPUs achieves speedup up to 11.28 on a Tesla K20m GPU compared to the sequential MAFFT 7.015. PMID- 26357091 TI - Predicting Protein Function Using Multiple Kernels. AB - High-throughput experimental techniques provide a wide variety of heterogeneous proteomic data sources. To exploit the information spread across multiple sources for protein function prediction, these data sources are transformed into kernels and then integrated into a composite kernel. Several methods first optimize the weights on these kernels to produce a composite kernel, and then train a classifier on the composite kernel. As such, these approaches result in an optimal composite kernel, but not necessarily in an optimal classifier. On the other hand, some approaches optimize the loss of binary classifiers and learn weights for the different kernels iteratively. For multi-class or multi-label data, these methods have to solve the problem of optimizing weights on these kernels for each of the labels, which are computationally expensive and ignore the correlation among labels. In this paper, we propose a method called Predicting Protein Function using Multiple Kernels (ProMK). ProMK iteratively optimizes the phases of learning optimal weights and reduces the empirical loss of multi-label classifier for each of the labels simultaneously. ProMK can integrate kernels selectively and downgrade the weights on noisy kernels. We investigate the performance of ProMK on several publicly available protein function prediction benchmarks and synthetic datasets. We show that the proposed approach performs better than previously proposed protein function prediction approaches that integrate multiple data sources and multi-label multiple kernel learning methods. The codes of our proposed method are available at https://sites.google.com/site/guoxian85/promk. PMID- 26357092 TI - Tractable Cases of (*,2)-Bounded Parsimony Haplotyping. AB - Parsimony haplotyping is the problem of finding a set of haplotypes of minimum cardinality that explains a given set of genotypes, where a genotype is explained by two haplotypes if it can be obtained as a combination of the two. This problem is NP-complete in the general case, but polynomially solvable for (k, l)-bounded instances for certain k and l. Here, k denotes the maximum number of ambiguous sites in any genotype, and l is the maximum number of genotypes that are ambiguous at the same site. Only the complexity of the (*, 2)-bounded problem is still unknown, where * denotes no restriction. It has been proved that (*, 2) bounded instances have compatibility graphs that can be constructed from cliques and circuits by pasting along an edge. In this paper, we give a constructive proof of the fact that (*, 2)-bounded instances are polynomially solvable if the compatibility graph is constructed by pasting cliques, trees and circuits along a bounded number of edges. We obtain this proof by solving a slightly generalized problem on circuits, trees and cliques respectively, and arguing that all possible combinations of optimal solutions for these graphs that are pasted along a bounded number of edges can be enumerated efficiently. PMID- 26357093 TI - WAVE: Interactive Wave-based Sound Propagation for Virtual Environments. AB - We present an interactive wave-based sound propagation system that generates accurate, realistic sound in virtual environments for dynamic (moving) sources and listeners. We propose a novel algorithm to accurately solve the wave equation for dynamic sources and listeners using a combination of precomputation techniques and GPU-based runtime evaluation. Our system can handle large environments typically used in VR applications, compute spatial sound corresponding to listener's motion (including head tracking) and handle both omnidirectional and directional sources, all at interactive rates. As compared to prior wave-based techniques applied to large scenes with moving sources, we observe significant improvement in runtime memory. The overall sound-propagation and rendering system has been integrated with the Half-Life 2 game engine, Oculus Rift head-mounted display, and the Xbox game controller to enable users to experience high-quality acoustic effects (e.g., amplification, diffraction low passing, high-order scattering) and spatial audio, based on their interactions in the VR application. We provide the results of preliminary user evaluations, conducted to study the impact of wave-based acoustic effects and spatial audio on users' navigation performance in virtual environments. PMID- 26357094 TI - Fast Physically Accurate Rendering of Multimodal Signatures of Distributed Fracture in Heterogeneous Materials. AB - This paper proposes a fast, physically accurate method for synthesizing multimodal, acoustic and haptic, signatures of distributed fracture in quasi brittle heterogeneous materials, such as wood, granular media, or other fiber composites. Fracture processes in these materials are challenging to simulate with existing methods, due to the prevalence of large numbers of disordered, quasi-random spatial degrees of freedom, representing the complex physical state of a sample over the geometric volume of interest. Here, I develop an algorithm for simulating such processes, building on a class of statistical lattice models of fracture that have been widely investigated in the physics literature. This algorithm is enabled through a recently published mathematical construction based on the inverse transform method of random number sampling. It yields a purely time domain stochastic jump process representing stress fluctuations in the medium. The latter can be readily extended by a mean field approximation that captures the averaged constitutive (stress-strain) behavior of the material. Numerical simulations and interactive examples demonstrate the ability of these algorithms to generate physically plausible acoustic and haptic signatures of fracture in complex, natural materials interactively at audio sampling rates. PMID- 26357095 TI - Aggregate Constraints for Virtual Manipulation with Soft Fingers. AB - Interactive dexterous manipulation of virtual objects remains a complex challenge that requires both appropriate hand models and accurate physically-based simulation of interactions. In this paper, we propose an approach based on novel aggregate constraints for simulating dexterous grasping using soft fingers. Our approach aims at improving the computation of contact mechanics when many contact points are involved, by aggregating the multiple contact constraints into a minimal set of constraints. We also introduce a method for non-uniform pressure distribution over the contact surface, to adapt the response when touching sharp edges. We use the Coulomb-Contensou friction model to efficiently simulate tangential and torsional friction. We show through different use cases that our aggregate constraint formulation is well-suited for simulating interactively dexterous manipulation of virtual objects through soft fingers, and efficiently reduces the computation time of constraint solving. PMID- 26357096 TI - Extended Depth-of-Field Projector by Fast Focal Sweep Projection. AB - A simple and cost-efficient method for extending a projector's depth-of-field (DOF) is proposed. By leveraging liquid lens technology, we can periodically modulate the focal length of a projector at a frequency that is higher than the critical flicker fusion (CFF) frequency. Fast periodic focal length modulation results in forward and backward sweeping of focusing distance. Fast focal sweep projection makes the point spread function (PSF) of each projected pixel integrated over a sweep period (IPSF; integrated PSF) nearly invariant to the distance from the projector to the projection surface as long as it is positioned within sweep range. This modulation is not perceivable by human observers. Once we compensate projection images for the IPSF, the projected results can be focused at any point within the range. Consequently, the proposed method requires only a single offline PSF measurement; thus, it is an open-loop process. We have proved the approximate invariance of the projector's IPSF both numerically and experimentally. Through experiments using a prototype system, we have confirmed that the image quality of the proposed method is superior to that of normal projection with fixed focal length. In addition, we demonstrate that a structured light pattern projection technique using the proposed method can measure the shape of an object with large depth variances more accurately than normal projection techniques. PMID- 26357097 TI - Light-Field Correction for Spatial Calibration of Optical See-Through Head Mounted Displays. AB - A critical requirement for AR applications with Optical See-Through Head-Mounted Displays (OST-HMD) is to project 3D information correctly into the current viewpoint of the user - more particularly, according to the user's eye position. Recently-proposed interaction-free calibration methods [16], [17] automatically estimate this projection by tracking the user's eye position, thereby freeing users from tedious manual calibrations. However, the method is still prone to contain systematic calibration errors. Such errors stem from eye-/HMD-related factors and are not represented in the conventional eye-HMD model used for HMD calibration. This paper investigates one of these factors - the fact that optical elements of OST-HMDs distort incoming world-light rays before they reach the eye, just as corrective glasses do. Any OST-HMD requires an optical element to display a virtual screen. Each such optical element has different distortions. Since users see a distorted world through the element, ignoring this distortion degenerates the projection quality. We propose a light-field correction method, based on a machine learning technique, which compensates the world-scene distortion caused by OST-HMD optics. We demonstrate that our method reduces the systematic error and significantly increases the calibration accuracy of the interaction-free calibration. PMID- 26357098 TI - Corneal-Imaging Calibration for Optical See-Through Head-Mounted Displays. AB - In recent years optical see-through head-mounted displays (OST-HMDs) have moved from conceptual research to a market of mass-produced devices with new models and applications being released continuously. It remains challenging to deploy augmented reality (AR) applications that require consistent spatial visualization. Examples include maintenance, training and medical tasks, as the view of the attached scene camera is shifted from the user's view. A calibration step can compute the relationship between the HMD-screen and the user's eye to align the digital content. However, this alignment is only viable as long as the display does not move, an assumption that rarely holds for an extended period of time. As a consequence, continuous recalibration is necessary. Manual calibration methods are tedious and rarely support practical applications. Existing automated methods do not account for user-specific parameters and are error prone. We propose the combination of a pre-calibrated display with a per-frame estimation of the user's cornea position to estimate the individual eye center and continuously recalibrate the system. With this, we also obtain the gaze direction, which allows for instantaneous uncalibrated eye gaze tracking, without the need for additional hardware and complex illumination. Contrary to existing methods, we use simple image processing and do not rely on iris tracking, which is typically noisy and can be ambiguous. Evaluation with simulated and real data shows that our approach achieves a more accurate and stable eye pose estimation, which results in an improved and practical calibration with a largely improved distribution of projection error. PMID- 26357099 TI - Subjective Evaluation of a Semi-Automatic Optical See-Through Head-Mounted Display Calibration Technique. AB - With the growing availability of optical see-through (OST) head-mounted displays (HMDs) there is a present need for robust, uncomplicated, and automatic calibration methods suited for non-expert users. This work presents the results of a user study which both objectively and subjectively examines registration accuracy produced by three OST HMD calibration methods: (1) SPAAM, (2) Degraded SPAAM, and (3) Recycled INDICA, a recently developed semi-automatic calibration method. Accuracy metrics used for evaluation include subject provided quality values and error between perceived and absolute registration coordinates. Our results show all three calibration methods produce very accurate registration in the horizontal direction but caused subjects to perceive the distance of virtual objects to be closer than intended. Surprisingly, the semi-automatic calibration method produced more accurate registration vertically and in perceived object distance overall. User assessed quality values were also the highest for Recycled INDICA, particularly when objects were shown at distance. The results of this study confirm that Recycled INDICA is capable of producing equal or superior on screen registration compared to common OST HMD calibration methods. We also identify a potential hazard in using reprojection error as a quantitative analysis technique to predict registration accuracy. We conclude with discussing the further need for examining INDICA calibration in binocular HMD systems, and the present possibility for creation of a closed-loop continuous calibration method for OST Augmented Reality. PMID- 26357100 TI - 3D Finger CAPE: Clicking Action and Position Estimation under Self-Occlusions in Egocentric Viewpoint. AB - In this paper we present a novel framework for simultaneous detection of click action and estimation of occluded fingertip positions from egocentric viewed single-depth image sequences. For the detection and estimation, a novel probabilistic inference based on knowledge priors of clicking motion and clicked position is presented. Based on the detection and estimation results, we were able to achieve a fine resolution level of a bare hand-based interaction with virtual objects in egocentric viewpoint. Our contributions include: (i) a rotation and translation invariant finger clicking action and position estimation using the combination of 2D image-based fingertip detection with 3D hand posture estimation in egocentric viewpoint. (ii) a novel spatio-temporal random forest, which performs the detection and estimation efficiently in a single framework. We also present (iii) a selection process utilizing the proposed clicking action detection and position estimation in an arm reachable AR/VR space, which does not require any additional device. Experimental results show that the proposed method delivers promising performance under frequent self-occlusions in the process of selecting objects in AR/VR space whilst wearing an egocentric-depth camera attached HMD. PMID- 26357101 TI - Teaming Up with Virtual Humans: How Other People Change Our Perceptions of and Behavior with Virtual Teammates. AB - In this paper we present a study exploring whether the physical presence of another human changes how people perceive and behave with virtual teammates. We conducted a study (n = 69) in which nurses worked with a simulated health care team to prepare a patient for surgery. The agency of participants' teammates was varied between conditions; participants either worked with a virtual surgeon and a virtual anesthesiologist, a human confederate playing a surgeon and a virtual anesthesiologist, or a virtual surgeon and a human confederate playing an anesthesiologist. While participants perceived the human confederates to have more social presence (p <; 0.01), participants did not preferentially agree with their human team members. We also observed an interaction effect between agency and behavioral realism. Participants experienced less social presence from the virtual anesthesiologist, whose behavior was less in line with participants' expectations, when a human surgeon was present. PMID- 26357102 TI - Going Through, Going Around: A Study on Individual Avoidance of Groups. AB - When avoiding a group, a walker has two possibilities: either he goes through it or around it. Going through very dense groups or around huge ones would not seem natural and could break any sense of presence in a virtual environment. This paper aims to enable crowd simulators to handle such situations correctly. To this end, we need to understand how real humans decide to go through or around groups. As a first hypothesis, we apply the Principle of Minimum Energy (PME) on different group sizes and density. According to this principle, a walker should go around small and dense groups whereas he should go through large and sparse groups. Such principle has already been used for crowd simulation; the novelty here is to apply it to decide on a global avoidance strategy instead of local adaptations only. Our study quantifies decision thresholds. However, PME leaves some inconclusive situations for which the two solutions paths have similar energetic costs. In a second part, we propose an experiment to corroborate PME decisions thresholds with real observations. As controlling the factors of an experiment with many people is extremely hard, we propose to use Virtual Reality as a new method to observe human behavior. This work represents the first crowd simulation algorithm component directly designed from a VR-based study. We also consider the role of secondary factors in inconclusive situations. We show the influence of the group appearance and direction of relative motion in the decision process. Finally, we draw some guidelines to integrate our conclusions to existing crowd simulators and show an example of such integration. We evaluate the achieved improvements. PMID- 26357103 TI - Assessing Knowledge Retention of an Immersive Serious Game vs. a Traditional Education Method in Aviation Safety. AB - Thanks to the increasing availability of consumer head-mounted displays, educational applications of immersive VR could now reach to the general public, especially if they include gaming elements (immersive serious games). Safety education of citizens could be a particularly promising domain for immersive serious games, because people tend not to pay attention to and benefit from current safety materials. In this paper, we propose an HMD-based immersive game for educating passengers about aviation safety that allows players to experience a serious aircraft emergency with the goal of surviving it. We compare the proposed approach to a traditional aviation safety education method (the safety card) used by airlines. Unlike most studies of VR for safety knowledge acquisition, we do not focus only on assessing learning immediately after the experience but we extend our attention to knowledge retention over a longer time span. This is a fundamental requirement, because people need to retain safety procedures in order to apply them when faced with danger. A knowledge test administered before, immediately after and one week after the experimental condition showed that the immersive serious game was superior to the safety card. Moreover, subjective as well as physiological measurements employed in the study showed that the immersive serious game was more engaging and fear-arousing than the safety card, a factor that can contribute to explain the obtained superior retention, as we discuss in the paper. PMID- 26357104 TI - Cognitive Resource Demands of Redirected Walking. AB - Redirected walking allows users to walk through a large-scale immersive virtual environment (IVE) while physically remaining in a reasonably small workspace. Therefore, manipulations are applied to virtual camera motions so that the user's self-motion in the virtual world differs from movements in the real world. Previous work found that the human perceptual system tolerates a certain amount of inconsistency between proprioceptive, vestibular and visual sensation in IVEs, and even compensates for slight discrepancies with recalibrated motor commands. Experiments showed that users are not able to detect an inconsistency if their physical path is bent with a radius of at least 22 meters during virtual straightforward movements. If redirected walking is applied in a smaller workspace, manipulations become noticeable, but users are still able to move through a potentially infinitely large virtual world by walking. For this semi natural form of locomotion, the question arises if such manipulations impose cognitive demands on the user, which may compete with other tasks in IVEs for finite cognitive resources. In this article we present an experiment in which we analyze the mutual influence between redirected walking and verbal as well as spatial working memory tasks using a dual-tasking method. The results show an influence of redirected walking on verbal as well as spatial working memory tasks, and we also found an effect of cognitive tasks on walking behavior. We discuss the implications and provide guidelines for using redirected walking in virtual reality laboratories. PMID- 26357105 TI - Subliminal Reorientation and Repositioning in Immersive Virtual Environments using Saccadic Suppression. AB - Virtual reality strives to provide a user with an experience of a simulated world that feels as natural as the real world. Yet, to induce this feeling, sometimes it becomes necessary for technical reasons to deviate from a one-to-one correspondence between the real and the virtual world, and to reorient or reposition the user's viewpoint. Ideally, users should not notice the change of the viewpoint to avoid breaks in perceptual continuity. Saccades, the fast eye movements that we make in order to switch gaze from one object to another, produce a visual discontinuity on the retina, but this is not perceived because the visual system suppresses perception during saccades. As a consequence, our perception fails to detect rotations of the visual scene during saccades. We investigated whether saccadic suppression of image displacement (SSID) can be used in an immersive virtual environment (VE) to unconsciously rotate and translate the observer's viewpoint. To do this, the scene changes have to be precisely time-locked to the saccade onset. We used electrooculography (EOG) for eye movement tracking and assessed the performance of two modified eye movement classification algorithms for the challenging task of online saccade detection that is fast enough for SSID. We investigated the sensitivity of participants to translations (forward/backward) and rotations (in the transverse plane) during trans-saccadic scene changes. We found that participants were unable to detect approximately +/-0.5m translations along the line of gaze and +/-5 degrees rotations in the transverse plane during saccades with an amplitude of 15 degrees . If the user stands still, our approach exploiting SSID thus provides the means to unconsciously change the user's virtual position and/or orientation. For future research and applications, exploiting SSID has the potential to improve existing redirected walking and change blindness techniques for unlimited navigation through arbitrarily-sized VEs by real walking. PMID- 26357106 TI - Generalized Topological Simplification of Scalar Fields on Surfaces. AB - We present a combinatorial algorithm for the general topological simplification of scalar fields on surfaces. Given a scalar field f, our algorithm generates a simplified field g that provably admits only critical points from a constrained subset of the singularities of f, while guaranteeing a small distance ||f - g||infinity for data-fitting purpose. In contrast to previous algorithms, our approach is oblivious to the strategy used for selecting features of interest and allows critical points to be removed arbitrarily. When topological persistence is used to select the features of interest, our algorithm produces a standard epsilon-simplification. Our approach is based on a new iterative algorithm for the constrained reconstruction of sub- and sur-level sets. Extensive experiments show that the number of iterations required for our algorithm to converge is rarely greater than 2 and never greater than 5, yielding O(n log(n)) practical time performances. The algorithm handles triangulated surfaces with or without boundary and is robust to the presence of multi-saddles in the input. It is simple to implement, fast in practice and more general than previous techniques. Practically, our approach allows a user to arbitrarily simplify the topology of an input function and robustly generate the corresponding simplified function. An appealing application area of our algorithm is in scalar field design since it enables, without any threshold parameter, the robust pruning of topological noise as selected by the user. This is needed for example to get rid of inaccuracies introduced by numerical solvers, thereby providing topological guarantees needed for certified geometry processing. Experiments show this ability to eliminate numerical noise as well as validate the time efficiency and accuracy of our algorithm. We provide a lightweight C++ implementation as supplemental material that can be used for topological cleaning on surface meshes. PMID- 26357107 TI - Computing Morse-Smale Complexes with Accurate Geometry. AB - Topological techniques have proven highly successful in analyzing and visualizing scientific data. As a result, significant efforts have been made to compute structures like the Morse-Smale complex as robustly and efficiently as possible. However, the resulting algorithms, while topologically consistent, often produce incorrect connectivity as well as poor geometry. These problems may compromise or even invalidate any subsequent analysis. Moreover, such techniques may fail to improve even when the resolution of the domain mesh is increased, thus producing potentially incorrect results even for highly resolved functions. To address these problems we introduce two new algorithms: (i) a randomized algorithm to compute the discrete gradient of a scalar field that converges under refinement; and (ii) a deterministic variant which directly computes accurate geometry and thus correct connectivity of the MS complex. The first algorithm converges in the sense that on average it produces the correct result and its standard deviation approaches zero with increasing mesh resolution. The second algorithm uses two ordered traversals of the function to integrate the probabilities of the first to extract correct (near optimal) geometry and connectivity. We present an extensive empirical study using both synthetic and real-world data and demonstrates the advantages of our algorithms in comparison with several popular approaches. PMID- 26357108 TI - Visualization of Temporal Similarity in Field Data. AB - This paper presents a visualization approach for detecting and exploring similarity in the temporal variation of field data. We provide an interactive technique for extracting correlations from similarity matrices which capture temporal similarity of univariate functions. We make use of the concept to extract periodic and quasiperiodic behavior at single (spatial) points as well as similarity between different locations within a field and also between different data sets. The obtained correlations are utilized for visual exploration of both temporal and spatial relationships in terms of temporal similarity. Our entire pipeline offers visual interaction and inspection, allowing for the flexibility that in particular time-dependent data analysis techniques require. We demonstrate the utility and versatility of our approach by applying our implementation to data from both simulation and measurement. PMID- 26357109 TI - Visualizing Nuclear Scission through a Multifield Extension of Topological Analysis. AB - In nuclear science, density functional theory (DFT) is a powerful tool to model the complex interactions within the atomic nucleus, and is the primary theoretical approach used by physicists seeking a better understanding of fission. However DFT simulations result in complex multivariate datasets in which it is difficult to locate the crucial 'scission' point at which one nucleus fragments into two, and to identify the precursors to scission. The Joint Contour Net (JCN) has recently been proposed as a new data structure for the topological analysis of multivariate scalar fields, analogous to the contour tree for univariate fields. This paper reports the analysis of DFT simulations using the JCN, the first application of the JCN technique to real data. It makes three contributions to visualization: (i) a set of practical methods for visualizing the JCN, (ii) new insight into the detection of nuclear scission, and (iii) an analysis of aesthetic criteria to drive further work on representing the JCN. PMID- 26357110 TI - Augmented Topological Descriptors of Pore Networks for Material Science. AB - One potential solution to reduce the concentration of carbon dioxide in the atmosphere is the geologic storage of captured CO2 in underground rock formations, also known as carbon sequestration. There is ongoing research to guarantee that this process is both efficient and safe. We describe tools that provide measurements of media porosity, and permeability estimates, including visualization of pore structures. Existing standard algorithms make limited use of geometric information in calculating permeability of complex microstructures. This quantity is important for the analysis of biomineralization, a subsurface process that can affect physical properties of porous media. This paper introduces geometric and topological descriptors that enhance the estimation of material permeability. Our analysis framework includes the processing of experimental data, segmentation, and feature extraction and making novel use of multiscale topological analysis to quantify maximum flow through porous networks. We illustrate our results using synchrotron-based X-ray computed microtomography of glass beads during biomineralization. We also benchmark the proposed algorithms using simulated data sets modeling jammed packed bead beds of a monodispersive material. PMID- 26357111 TI - KnotPad: Visualizing and Exploring Knot Theory with Fluid Reidemeister Moves. AB - We present KnotPad, an interactive paper-like system for visualizing and exploring mathematical knots; we exploit topological drawing and math-aware deformation methods in particular to enable and enrich our interactions with knot diagrams. Whereas most previous efforts typically employ physically based modeling to simulate the 3D dynamics of knots and ropes, our tool offers a Reidemeister move based interactive environment that is much closer to the topological problems being solved in knot theory, yet without interfering with the traditional advantages of paper-based analysis and manipulation of knot diagrams. Drawing knot diagrams with many crossings and producing their equivalent is quite challenging and error-prone. KnotPad can restrict user manipulations to the three types of Reidemeister moves, resulting in a more fluid yet mathematically correct user experience with knots. For our principal test case of mathematical knots, KnotPad permits us to draw and edit their diagrams empowered by a family of interactive techniques. Furthermore, we exploit supplementary interface elements to enrich the user experiences. For example, KnotPad allows one to pull and drag on knot diagrams to produce mathematically valid moves. Navigation enhancements in KnotPad provide still further improvement: by remembering and displaying the sequence of valid moves applied during the entire interaction, KnotPad allows a much cleaner exploratory interface for the user to analyze and study knot equivalence. All these methods combine to reveal the complex spatial relationships of knot diagrams with a mathematically true and rich user experience. PMID- 26357112 TI - Visualization of Electrostatic Dipoles in Molecular Dynamics of Metal Oxides. AB - Metal oxides are important for many technical applications. For example alumina (aluminum oxide) is the most commonly-used ceramic in microelectronic devices thanks to its excellent properties. Experimental studies of these materials are increasingly supplemented with computer simulations. Molecular dynamics (MD) simulations can reproduce the material behavior very well and are now reaching time scales relevant for interesting processes like crack propagation. In this work we focus on the visualization of induced electric dipole moments on oxygen atoms in crack propagation simulations. The straightforward visualization using glyphs for the individual atoms, simple shapes like spheres or arrows, is insufficient for providing information about the data set as a whole. As our contribution we show for the first time that fractional anisotropy values computed from the local neighborhood of individual atoms of MD simulation data depict important information about relevant properties of the field of induced electric dipole moments. Iso surfaces in the field of fractional anisotropy as well as adjustments of the glyph representation allow the user to identify regions of correlated orientation. We present novel and relevant findings for the application domain resulting from these visualizations, like the influence of mechanical forces on the electrostatic properties. PMID- 26357113 TI - Cumulative Heat Diffusion Using Volume Gradient Operator for Volume Analysis. AB - We introduce a simple, yet powerful method called the Cumulative Heat Diffusion for shape-based volume analysis, while drastically reducing the computational cost compared to conventional heat diffusion. Unlike the conventional heat diffusion process, where the diffusion is carried out by considering each node separately as the source, we simultaneously consider all the voxels as sources and carry out the diffusion, hence the term cumulative heat diffusion. In addition, we introduce a new operator that is used in the evaluation of cumulative heat diffusion called the Volume Gradient Operator (VGO). VGO is a combination of the LBO and a data-driven operator which is a function of the half gradient. The half gradient is the absolute value of the difference between the voxel intensities. The VGO by its definition captures the local shape information and is used to assign the initial heat values. Furthermore, VGO is also used as the weighting parameter for the heat diffusion process. We demonstrate that our approach can robustly extract shape-based features and thus forms the basis for an improved classification and exploration of features based on shape. PMID- 26357114 TI - A Novel Approach to Visualizing Dark Matter Simulations. AB - In the last decades cosmological N-body dark matter simulations have enabled ab initio studies of the formation of structure in the Universe. Gravity amplified small density fluctuations generated shortly after the Big Bang, leading to the formation of galaxies in the cosmic web. These calculations have led to a growing demand for methods to analyze time-dependent particle based simulations. Rendering methods for such N-body simulation data usually employ some kind of splatting approach via point based rendering primitives and approximate the spatial distributions of physical quantities using kernel interpolation techniques, common in SPH (Smoothed Particle Hydrodynamics)-codes. This paper proposes three GPU-assisted rendering approaches, based on a new, more accurate method to compute the physical densities of dark matter simulation data. It uses full phase-space information to generate a tetrahedral tessellation of the computational domain, with mesh vertices defined by the simulation's dark matter particle positions. Over time the mesh is deformed by gravitational forces, causing the tetrahedral cells to warp and overlap. The new methods are well suited to visualize the cosmic web. In particular they preserve caustics, regions of high density that emerge, when several streams of dark matter particles share the same location in space, indicating the formation of structures like sheets, filaments and halos. We demonstrate the superior image quality of the new approaches in a comparison with three standard rendering techniques for N-body simulation data. PMID- 26357116 TI - Evaluation of Fast-Forward Video Visualization. AB - We evaluate and compare video visualization techniques based on fast-forward. A controlled laboratory user study (n = 24) was conducted to determine the trade off between support of object identification and motion perception, two properties that have to be considered when choosing a particular fast-forward visualization. We compare four different visualizations: two representing the state-of-the-art and two new variants of visualization introduced in this paper. The two state-of-the-art methods we consider are frame-skipping and temporal blending of successive frames. Our object trail visualization leverages a combination of frame-skipping and temporal blending, whereas predictive trajectory visualization supports motion perception by augmenting the video frames with an arrow that indicates the future object trajectory. Our hypothesis was that each of the state-of-the-art methods satisfies just one of the goals: support of object identification or motion perception. Thus, they represent both ends of the visualization design. The key findings of the evaluation are that object trail visualization supports object identification, whereas predictive trajectory visualization is most useful for motion perception. However, frame skipping surprisingly exhibits reasonable performance for both tasks. Furthermore, we evaluate the subjective performance of three different playback speed visualizations for adaptive fast-forward, a subdomain of video fast forward. PMID- 26357115 TI - Visual Data Analysis as an Integral Part of Environmental Management. AB - The U.S. Department of Energy's (DOE) Office of Environmental Management (DOE/EM) currently supports an effort to understand and predict the fate of nuclear contaminants and their transport in natural and engineered systems. Geologists, hydrologists, physicists and computer scientists are working together to create models of existing nuclear waste sites, to simulate their behavior and to extrapolate it into the future. We use visualization as an integral part in each step of this process. In the first step, visualization is used to verify model setup and to estimate critical parameters. High-performance computing simulations of contaminant transport produces massive amounts of data, which is then analyzed using visualization software specifically designed for parallel processing of large amounts of structured and unstructured data. Finally, simulation results are validated by comparing simulation results to measured current and historical field data. We describe in this article how visual analysis is used as an integral part of the decision-making process in the planning of ongoing and future treatment options for the contaminated nuclear waste sites. Lessons learned from visually analyzing our large-scale simulation runs will also have an impact on deciding on treatment measures for other contaminated sites. PMID- 26357117 TI - Human Computation in Visualization: Using Purpose Driven Games for Robust Evaluation of Visualization Algorithms. AB - Due to the inherent characteristics of the visualization process, most of the problems in this field have strong ties with human cognition and perception. This makes the human brain and sensory system the only truly appropriate evaluation platform for evaluating and fine-tuning a new visualization method or paradigm. However, getting humans to volunteer for these purposes has always been a significant obstacle, and thus this phase of the development process has traditionally formed a bottleneck, slowing down progress in visualization research. We propose to take advantage of the newly emerging field of Human Computation (HC) to overcome these challenges. HC promotes the idea that rather than considering humans as users of the computational system, they can be made part of a hybrid computational loop consisting of traditional computation resources and the human brain and sensory system. This approach is particularly successful in cases where part of the computational problem is considered intractable using known computer algorithms but is trivial to common sense human knowledge. In this paper, we focus on HC from the perspective of solving visualization problems and also outline a framework by which humans can be easily seduced to volunteer their HC resources. We introduce a purpose-driven game titled "Disguise" which serves as a prototypical example for how the evaluation of visualization algorithms can be mapped into a fun and addicting activity, allowing this task to be accomplished in an extensive yet cost effective way. Finally, we sketch out a framework that transcends from the pure evaluation of existing visualization methods to the design of a new one. PMID- 26357118 TI - Evaluation of Multivariate Visualization on a Multivariate Task. AB - Multivariate visualization techniques have attracted great interest as the dimensionality of data sets grows. One premise of such techniques is that simultaneous visual representation of multiple variables will enable the data analyst to detect patterns amongst multiple variables. Such insights could lead to development of new techniques for rigorous (numerical) analysis of complex relationships hidden within the data. Two natural questions arise from this premise: Which multivariate visualization techniques are the most effective for high-dimensional data sets? How does the analysis task change this utility ranking? We present a user study with a new task to answer the first question. We provide some insights to the second question based on the results of our study and results available in the literature. Our task led to significant differences in error, response time, and subjective workload ratings amongst four visualization techniques. We implemented three integrated techniques (Data-driven Spots, Oriented Slivers, and Attribute Blocks), as well as a baseline case of separate grayscale images. The baseline case fared poorly on all three measures, whereas Datadriven Spots yielded the best accuracy and was among the best in response time. These results differ from comparisons of similar techniques with other tasks, and we review all the techniques, tasks, and results (from our work and previous work) to understand the reasons for this discrepancy. PMID- 26357119 TI - A Data-Driven Approach to Hue-Preserving Color-Blending. AB - Color mapping and semitransparent layering play an important role in many visualization scenarios, such as information visualization and volume rendering. The combination of color and transparency is still dominated by standard alpha compositing using the Porter-Duff over operator which can result in false colors with deceiving impact on the visualization. Other more advanced methods have also been proposed, but the problem is still far from being solved. Here we present an alternative to these existing methods specifically devised to avoid false colors and preserve visual depth ordering. Our approach is data driven and follows the recently formulated knowledge-assisted visualization (KAV) paradigm. Preference data, that have been gathered in web-based user surveys, are used to train a support-vector machine model for automatically predicting an optimized hue preserving blending. We have applied the resulting model to both volume rendering and a specific information visualization technique, illustrative parallel coordinate plots. Comparative renderings show a significant improvement over previous approaches in the sense that false colors are completely removed and important properties such as depth ordering and blending vividness are better preserved. Due to the generality of the defined data-driven blending operator, it can be easily integrated also into other visualization frameworks. PMID- 26357120 TI - Effects of Stereo and Screen Size on the Legibility of Three-Dimensional Streamtube Visualization. AB - We report the impact of display characteristics (stereo and size) on task performance in diffusion magnetic resonance imaging (DMRI) in a user study with 12 participants. The hypotheses were that (1) adding stereo and increasing display size would improve task accuracy and reduce completion time, and (2) the greater the complexity of a spatial task, the greater the benefits of an improved display. Thus we expected to see greater performance gains when detailed visual reasoning was required. Participants used dense streamtube visualizations to perform five representative tasks: (1) determine the higher average fractional anisotropy (FA) values between two regions, (2) find the endpoints of fiber tracts, (3) name a bundle, (4) mark a brain lesion, and (5) judge if tracts belong to the same bundle. Contrary to our hypotheses, we found the task completion time was not improved by the use of the larger display and that performance accuracy was hurt rather than helped by the introduction of stereo in our study with dense DMRI data. Bigger was not always better. Thus cautious should be taken when selecting displays for scientific visualization applications. We explored the results further using the body-scale unit and subjective size and stereo experiences. PMID- 26357121 TI - Analysis of Streamline Separation at Infinity Using Time-Discrete Markov Chains. AB - Existing methods for analyzing separation of streamlines are often restricted to a finite time or a local area. In our paper we introduce a new method that complements them by allowing an infinite-time-evaluation of steady planar vector fields. Our algorithm unifies combinatorial and probabilistic methods and introduces the concept of separation in time-discrete Markov-Chains. We compute particle distributions instead of the streamlines of single particles. We encode the flow into a map and then into a transition matrix for each time direction. Finally, we compare the results of our grid-independent algorithm to the popular Finite-Time-Lyapunov-Exponents and discuss the discrepancies. PMID- 26357122 TI - Derived Metric Tensors for Flow Surface Visualization. AB - Integral flow surfaces constitute a widely used flow visualization tool due to their capability to convey important flow information such as fluid transport, mixing, and domain segmentation. Current flow surface rendering techniques limit their expressiveness, however, by focusing virtually exclusively on displacement visualization, visually neglecting the more complex notion of deformation such as shearing and stretching that is central to the field of continuum mechanics. To incorporate this information into the flow surface visualization and analysis process, we derive a metric tensor field that encodes local surface deformations as induced by the velocity gradient of the underlying flow field. We demonstrate how properties of the resulting metric tensor field are capable of enhancing present surface visualization and generation methods and develop novel surface querying, sampling, and visualization techniques. The provided results show how this step towards unifying classic flow visualization and more advanced concepts from continuum mechanics enables more detailed and improved flow analysis. PMID- 26357123 TI - Lagrangian Coherent Structures for Design Analysis of Revolving Doors. AB - Room air flow and air exchange are important aspects for the design of energy efficient buildings. As a result, simulations are increasingly used prior to construction to achieve an energy-efficient design. We present a visual analysis of air flow generated at building entrances, which uses a combination of revolving doors and air curtains. The resulting flow pattern is challenging because of two interacting flow patterns: On the one hand, the revolving door acts as a pump, on the other hand, the air curtain creates a layer of uniformly moving warm air between the interior of the building and the revolving door. Lagrangian coherent structures (LCS), which by definition are flow barriers, are the method of choice for visualizing the separation and recirculation behavior of warm and cold air flow. The extraction of LCS is based on the finite-time Lyapunov exponent (FTLE) and makes use of a ridge definition which is consistent with the concept of weak LCS. Both FTLE computation and ridge extraction are done in a robust and efficient way by making use of the fast Fourier transform for computing scale-space derivatives. PMID- 26357124 TI - Turbulence Visualization at the Terascale on Desktop PCs. AB - Despite the ongoing efforts in turbulence research, the universal properties of the turbulence small-scale structure and the relationships between small- and large-scale turbulent motions are not yet fully understood. The visually guided exploration of turbulence features, including the interactive selection and simultaneous visualization of multiple features, can further progress our understanding of turbulence. Accomplishing this task for flow fields in which the full turbulence spectrum is well resolved is challenging on desktop computers. This is due to the extreme resolution of such fields, requiring memory and bandwidth capacities going beyond what is currently available. To overcome these limitations, we present a GPU system for feature-based turbulence visualization that works on a compressed flow field representation. We use a wavelet-based compression scheme including run-length and entropy encoding, which can be decoded on the GPU and embedded into brick-based volume ray-casting. This enables a drastic reduction of the data to be streamed from disk to GPU memory. Our system derives turbulence properties directly from the velocity gradient tensor, and it either renders these properties in turn or generates and renders scalar feature volumes. The quality and efficiency of the system is demonstrated in the visualization of two unsteady turbulence simulations, each comprising a spatio temporal resolution of 10244. On a desktop computer, the system can visualize each time step in 5 seconds, and it achieves about three times this rate for the visualization of a scalar feature volume. PMID- 26357125 TI - Automatic Detection and Visualization of Qualitative Hemodynamic Characteristics in Cerebral Aneurysms. AB - Cerebral aneurysms are a pathological vessel dilatation that bear a high risk of rupture. For the understanding and evaluation of the risk of rupture, the analysis of hemodynamic information plays an important role. Besides quantitative hemodynamic information, also qualitative flow characteristics, e.g., the inflow jet and impingement zone are correlated with the risk of rupture. However, the assessment of these two characteristics is currently based on an interactive visual investigation of the flow field, obtained by computational fluid dynamics (CFD) or blood flow measurements. We present an automatic and robust detection as well as an expressive visualization of these characteristics. The detection can be used to support a comparison, e.g., of simulation results reflecting different treatment options. Our approach utilizes local streamline properties to formalize the inflow jet and impingement zone. We extract a characteristic seeding curve on the ostium, on which an inflow jet boundary contour is constructed. Based on this boundary contour we identify the impingement zone. Furthermore, we present several visualization techniques to depict both characteristics expressively. Thereby, we consider accuracy and robustness of the extracted characteristics, minimal visual clutter and occlusions. An evaluation with six domain experts confirms that our approach detects both hemodynamic characteristics reasonably. PMID- 26357126 TI - Visualization of Astronomical Nebulae via Distributed Multi-GPU Compressed Sensing Tomography. AB - The 3D visualization of astronomical nebulae is a challenging problem since only a single 2D projection is observable from our fixed vantage point on Earth. We attempt to generate plausible and realistic looking volumetric visualizations via a tomographic approach that exploits the spherical or axial symmetry prevalent in some relevant types of nebulae. Different types of symmetry can be implemented by using different randomized distributions of virtual cameras. Our approach is based on an iterative compressed sensing reconstruction algorithm that we extend with support for position-dependent volumetric regularization and linear equality constraints. We present a distributed multi-GPU implementation that is capable of reconstructing high-resolution datasets from arbitrary projections. Its robustness and scalability are demonstrated for astronomical imagery from the Hubble Space Telescope. The resulting volumetric data is visualized using direct volume rendering. Compared to previous approaches, our method preserves a much higher amount of detail and visual variety in the 3D visualization, especially for objects with only approximate symmetry. PMID- 26357127 TI - Visualization of Flow Behavior in Earth Mantle Convection. AB - A fundamental characteristic of fluid flow is that it causes mixing: introduce a dye into a flow, and it will disperse. Mixing can be used as a method to visualize and characterize flow. Because mixing is a process that occurs over time, it is a 4D problem that presents a challenge for computation, visualization, and analysis. Motivated by a mixing problem in geophysics, we introduce a combination of methods to analyze, transform, and finally visualize mixing in simulations of convection in a self-gravitating 3D spherical shell representing convection in the Earth's mantle. Geophysicists use tools such as the finite element model CitcomS to simulate convection, and introduce massless, passive tracers to model mixing. The output of geophysical flow simulation is hard to analyze for domain experts because of overall data size and complexity. In addition, information overload and occlusion are problems when visualizing a whole-earth model. To address the large size of the data, we rearrange the simulation data using intelligent indexing for fast file access and efficient caching. To address information overload and interpret mixing, we compute tracer concentration statistics, which are used to characterize mixing in mantle convection models. Our visualization uses a specially tailored version of Direct Volume Rendering. The most important adjustment is the use of constant opacity. Because of this special area of application, i. e. the rendering of a spherical shell, many computations for volume rendering can be optimized. These optimizations are essential to a smooth animation of the time-dependent simulation data. Our results show how our system can be used to quickly assess the simulation output and test hypotheses regarding Earth's mantle convection. The integrated processing pipeline helps geoscientists to focus on their main task of analyzing mantle homogenization. PMID- 26357128 TI - Interactive Retro-Deformation of Terrain for Reconstructing 3D Fault Displacements. AB - Planetary topography is the result of complex interactions between geological processes, of which faulting is a prominent component. Surface-rupturing earthquakes cut and move landforms which develop across active faults, producing characteristic surface displacements across the fault. Geometric models of faults and their associated surface displacements are commonly applied to reconstruct these offsets to enable interpretation of the observed topography. However, current 2D techniques are limited in their capability to convey both the three dimensional kinematics of faulting and the incremental sequence of events required by a given reconstruction. Here we present a real-time system for interactive retro-deformation of faulted topography to enable reconstruction of fault displacement within a high-resolution (sub 1m/pixel) 3D terrain visualization. We employ geometry shaders on the GPU to intersect the surface mesh with fault-segments interactively specified by the user and transform the resulting surface blocks in realtime according to a kinematic model of fault motion. Our method facilitates a human-in-the-loop approach to reconstruction of fault displacements by providing instant visual feedback while exploring the parameter space. Thus, scientists can evaluate the validity of traditional point to-point reconstructions by visually examining a smooth interpolation of the displacement in 3D. We show the efficacy of our approach by using it to reconstruct segments of the San Andreas fault, California as well as a graben structure in the Noctis Labyrinthus region on Mars. PMID- 26357129 TI - A Visual Analysis Concept for the Validation of Geoscientific Simulation Models. AB - Geoscientific modeling and simulation helps to improve our understanding of the complex Earth system. During the modeling process, validation of the geoscientific model is an essential step. In validation, it is determined whether the model output shows sufficient agreement with observation data. Measures for this agreement are called goodness of fit. In the geosciences, analyzing the goodness of fit is challenging due to its manifold dependencies: 1) The goodness of fit depends on the model parameterization, whose precise values are not known. 2) The goodness of fit varies in space and time due to the spatio-temporal dimension of geoscientific models. 3) The significance of the goodness of fit is affected by resolution and preciseness of available observational data. 4) The correlation between goodness of fit and underlying modeled and observed values is ambiguous. In this paper, we introduce a visual analysis concept that targets these challenges in the validation of geoscientific models - specifically focusing on applications where observation data is sparse, unevenly distributed in space and time, and imprecise, which hinders a rigorous analytical approach. Our concept, developed in close cooperation with Earth system modelers, addresses the four challenges by four tailored visualization components. The tight linking of these components supports a twofold interactive drill-down in model parameter space and in the set of data samples, which facilitates the exploration of the numerous dependencies of the goodness of fit. We exemplify our visualization concept for geoscientific modeling of glacial isostatic adjustments in the last 100,000 years, validated against sea levels indicators - a prominent example for sparse and imprecise observation data. An initial use case and feedback from Earth system modelers indicate that our visualization concept is a valuable complement to the range of validation methods. PMID- 26357130 TI - SeiVis: An Interactive Visual Subsurface Modeling Application. AB - The most important resources to fulfill today's energy demands are fossil fuels, such as oil and natural gas. When exploiting hydrocarbon reservoirs, a detailed and credible model of the subsurface structures is crucial in order to minimize economic and ecological risks. Creating such a model is an inverse problem: reconstructing structures from measured reflection seismics. The major challenge here is twofold: First, the structures in highly ambiguous seismic data are interpreted in the time domain. Second, a velocity model has to be built from this interpretation to match the model to depth measurements from wells. If it is not possible to obtain a match at all positions, the interpretation has to be updated, going back to the first step. This results in a lengthy back and forth between the different steps, or in an unphysical velocity model in many cases. This paper presents a novel, integrated approach to interactively creating subsurface models from reflection seismics. It integrates the interpretation of the seismic data using an interactive horizon extraction technique based on piecewise global optimization with velocity modeling. Computing and visualizing the effects of changes to the interpretation and velocity model on the depth converted model on the fly enables an integrated feedback loop that enables a completely new connection of the seismic data in time domain and well data in depth domain. Using a novel joint time/depth visualization, depicting side-by side views of the original and the resulting depth-converted data, domain experts can directly fit their interpretation in time domain to spatial ground truth data. We have conducted a domain expert evaluation, which illustrates that the presented workflow enables the creation of exact subsurface models much more rapidly than previous approaches. PMID- 26357131 TI - WYSIWYP: What You See Is What You Pick. AB - Scientists, engineers and physicians are used to analyze 3D data with slice-based visualizations. Radiologists for example are trained to read slices of medical imaging data. Despite the numerous examples of sophisticated 3D rendering techniques, domain experts, who still prefer slice-based visualization do not consider these to be very useful. Since 3D renderings have the advantage of providing an overview at a glance, while 2D depictions better serve detailed analyses, it is of general interest to better combine these methods. Recently there have been attempts to bridge this gap between 2D and 3D renderings. These attempts include specialized techniques for volume picking in medical imaging data that result in repositioning slices. In this paper, we present a new volume picking technique called WYSIWYP ("what you see is what you pick") that, in contrast to previous work, does not require pre-segmented data or metadata and thus is more generally applicable. The positions picked by our method are solely based on the data itself, the transfer function, and the way the volumetric rendering is perceived by the user. To demonstrate the utility of the proposed method, we apply it to automated positioning of slices in volumetric scalar fields from various application areas. Finally, we present results of a user study in which 3D locations selected by users are compared to those resulting from WYSIWYP. The user study confirms our claim that the resulting positions correlate well with those perceived by the user. PMID- 26357132 TI - Efficient Structure-Aware Selection Techniques for 3D Point Cloud Visualizations with 2DOF Input. AB - Data selection is a fundamental task in visualization because it serves as a pre requisite to many follow-up interactions. Efficient spatial selection in 3D point cloud datasets consisting of thousands or millions of particles can be particularly challenging. We present two new techniques, TeddySelection and CloudLasso, that support the selection of subsets in large particle 3D datasets in an interactive and visually intuitive manner. Specifically, we describe how to spatially select a subset of a 3D particle cloud by simply encircling the target particles on screen using either the mouse or direct-touch input. Based on the drawn lasso, our techniques automatically determine a bounding selection surface around the encircled particles based on their density. This kind of selection technique can be applied to particle datasets in several application domains. TeddySelection and CloudLasso reduce, and in some cases even eliminate, the need for complex multi-step selection processes involving Boolean operations. This was confirmed in a formal, controlled user study in which we compared the more flexible CloudLasso technique to the standard cylinder-based selection technique. This study showed that the former is consistently more efficient than the latter in several cases the CloudLasso selection time was half that of the corresponding cylinder-based selection. PMID- 26357133 TI - Sketching Uncertainty into Simulations. AB - In a variety of application areas, the use of simulation steering in decision making is limited at best. Research focusing on this problem suggests that most user interfaces are too complex for the end user. Our goal is to let users create and investigate multiple, alternative scenarios without the need for special simulation expertise. To simplify the specification of parameters, we move from a traditional manipulation of numbers to a sketch-based input approach. Users steer both numeric parameters and parameters with a spatial correspondence by sketching a change onto the rendering. Special visualizations provide immediate visual feedback on how the sketches are transformed into boundary conditions of the simulation models. Since uncertainty with respect to many intertwined parameters plays an important role in planning, we also allow the user to intuitively setup complete value ranges, which are then automatically transformed into ensemble simulations. The interface and the underlying system were developed in collaboration with experts in the field of flood management. The real-world data they have provided has allowed us to construct scenarios used to evaluate the system. These were presented to a variety of flood response personnel, and their feedback is discussed in detail in the paper. The interface was found to be intuitive and relevant, although a certain amount of training might be necessary. PMID- 26357134 TI - A Perceptual-Statistics Shading Model. AB - The process of surface perception is complex and based on several influencing factors, e.g., shading, silhouettes, occluding contours, and top down cognition. The accuracy of surface perception can be measured and the influencing factors can be modified in order to decrease the error in perception. This paper presents a novel concept of how a perceptual evaluation of a visualization technique can contribute to its redesign with the aim of improving the match between the distal and the proximal stimulus. During analysis of data from previous perceptual studies, we observed that the slant of 3D surfaces visualized on 2D screens is systematically underestimated. The visible trends in the error allowed us to create a statistical model of the perceived surface slant. Based on this statistical model we obtained from user experiments, we derived a new shading model that uses adjusted surface normals and aims to reduce the error in slant perception. The result is a shape-enhancement of visualization which is driven by an experimentally-founded statistical model. To assess the efficiency of the statistical shading model, we repeated the evaluation experiment and confirmed that the error in perception was decreased. Results of both user experiments are publicly-available datasets. PMID- 26357135 TI - Visual Steering and Verification of Mass Spectrometry Data Factorization in Air Quality Research. AB - The study of aerosol composition for air quality research involves the analysis of high-dimensional single particle mass spectrometry data. We describe, apply, and evaluate a novel interactive visual framework for dimensionality reduction of such data. Our framework is based on non-negative matrix factorization with specifically defined regularization terms that aid in resolving mass spectrum ambiguity. Thereby, visualization assumes a key role in providing insight into and allowing to actively control a heretofore elusive data processing step, and thus enabling rapid analysis meaningful to domain scientists. In extending existing black box schemes, we explore design choices for visualizing, interacting with, and steering the factorization process to produce physically meaningful results. A domain-expert evaluation of our system performed by the air quality research experts involved in this effort has shown that our method and prototype admits the finding of unambiguous and physically correct lower dimensional basis transformations of mass spectrometry data at significantly increased speed and a higher degree of ease. PMID- 26357136 TI - Interactive Volume Exploration of Petascale Microscopy Data Streams Using a Visualization-Driven Virtual Memory Approach. AB - This paper presents the first volume visualization system that scales to petascale volumes imaged as a continuous stream of high-resolution electron microscopy images. Our architecture scales to dense, anisotropic petascale volumes because it: (1) decouples construction of the 3D multi-resolution representation required for visualization from data acquisition, and (2) decouples sample access time during ray-casting from the size of the multi resolution hierarchy. Our system is designed around a scalable multi-resolution virtual memory architecture that handles missing data naturally, does not pre compute any 3D multi-resolution representation such as an octree, and can accept a constant stream of 2D image tiles from the microscopes. A novelty of our system design is that it is visualization-driven: we restrict most computations to the visible volume data. Leveraging the virtual memory architecture, missing data are detected during volume ray-casting as cache misses, which are propagated backwards for on-demand out-of-core processing. 3D blocks of volume data are only constructed from 2D microscope image tiles when they have actually been accessed during ray-casting. We extensively evaluate our system design choices with respect to scalability and performance, compare to previous best-of-breed systems, and illustrate the effectiveness of our system for real microscopy data from neuroscience. PMID- 26357137 TI - An Adaptive Prediction-Based Approach to Lossless Compression of Floating-Point Volume Data. AB - In this work, we address the problem of lossless compression of scientific and medical floating-point volume data. We propose two prediction-based compression methods that share a common framework, which consists of a switched prediction scheme wherein the best predictor out of a preset group of linear predictors is selected. Such a scheme is able to adapt to different datasets as well as to varying statistics within the data. The first method, called APE (Adaptive Polynomial Encoder), uses a family of structured interpolating polynomials for prediction, while the second method, which we refer to as ACE (Adaptive Combined Encoder), combines predictors from previous work with the polynomial predictors to yield a more flexible, powerful encoder that is able to effectively decorrelate a wide range of data. In addition, in order to facilitate efficient visualization of compressed data, our scheme provides an option to partition floating-point values in such a way as to provide a progressive representation. We compare our two compressors to existing state-of-the-art lossless floating point compressors for scientific data, with our data suite including both computer simulations and observational measurements. The results demonstrate that our polynomial predictor, APE, is comparable to previous approaches in terms of speed but achieves better compression rates on average. ACE, our combined predictor, while somewhat slower, is able to achieve the best compression rate on all datasets, with significantly better rates on most of the datasets. PMID- 26357138 TI - On the Interpolation of Data with Normally Distributed Uncertainty for Visualization. AB - In many fields of science or engineering, we are confronted with uncertain data. For that reason, the visualization of uncertainty received a lot of attention, especially in recent years. In the majority of cases, Gaussian distributions are used to describe uncertain behavior, because they are able to model many phenomena encountered in science. Therefore, in most applications uncertain data is (or is assumed to be) Gaussian distributed. If such uncertain data is given on fixed positions, the question of interpolation arises for many visualization approaches. In this paper, we analyze the effects of the usual linear interpolation schemes for visualization of Gaussian distributed data. In addition, we demonstrate that methods known in geostatistics and machine learning have favorable properties for visualization purposes in this case. PMID- 26357139 TI - Coherency-Based Curve Compression for High-Order Finite Element Model Visualization. AB - Finite element (FE) models are frequently used in engineering and life sciences within time-consuming simulations. In contrast with the regular grid structure facilitated by volumetric data sets, as used in medicine or geosciences, FE models are defined over a non-uniform grid. Elements can have curved faces and their interior can be defined through high-order basis functions, which pose additional challenges when visualizing these models. During ray-casting, the uniformly distributed sample points along each viewing ray must be transformed into the material space defined within each element. The computational complexity of this transformation makes a straightforward approach inadequate for interactive data exploration. In this paper, we introduce a novel coherency-based method which supports the interactive exploration of FE models by decoupling the expensive world-to-material space transformation from the rendering stage, thereby allowing it to be performed within a precomputation stage. Therefore, our approach computes view-independent proxy rays in material space, which are clustered to facilitate data reduction. During rendering, these proxy rays are accessed, and it becomes possible to visually analyze high-order FE models at interactive frame rates, even when they are time-varying or consist of multiple modalities. Within this paper, we provide the necessary background about the FE data, describe our decoupling method, and introduce our interactive rendering algorithm. Furthermore, we provide visual results and analyze the error introduced by the presented approach. PMID- 26357140 TI - ElVis: A System for the Accurate and Interactive Visualization of High-Order Finite Element Solutions. AB - This paper presents the Element Visualizer (ElVis), a new, open-source scientific visualization system for use with high-order finite element solutions to PDEs in three dimensions. This system is designed to minimize visualization errors of these types of fields by querying the underlying finite element basis functions (e.g., high-order polynomials) directly, leading to pixel-exact representations of solutions and geometry. The system interacts with simulation data through runtime plugins, which only require users to implement a handful of operations fundamental to finite element solvers. The data in turn can be visualized through the use of cut surfaces, contours, isosurfaces, and volume rendering. These visualization algorithms are implemented using NVIDIA's OptiX GPU-based ray tracing engine, which provides accelerated ray traversal of the high-order geometry, and CUDA, which allows for effective parallel evaluation of the visualization algorithms. The direct interface between ElVis and the underlying data differentiates it from existing visualization tools. Current tools assume the underlying data is composed of linear primitives; high-order data must be interpolated with linear functions as a result. In this work, examples drawn from aerodynamic simulations-high-order discontinuous Galerkin finite element solutions of aerodynamic flows in particular-will demonstrate the superiority of ElVis' pixel-exact approach when compared with traditional linear-interpolation methods. Such methods can introduce a number of inaccuracies in the resulting visualization, making it unclear if visual artifacts are genuine to the solution data or if these artifacts are the result of interpolation errors. Linear methods additionally cannot properly visualize curved geometries (elements or boundaries) which can greatly inhibit developers' debugging efforts. As we will show, pixel exact visualization exhibits none of these issues, removing the visualization scheme as a source of uncertainty for engineers using ElVis. PMID- 26357141 TI - Fuzzy Volume Rendering. AB - In order to assess the reliability of volume rendering, it is necessary to consider the uncertainty associated with the volume data and how it is propagated through the volume rendering algorithm, as well as the contribution to uncertainty from the rendering algorithm itself. In this work, we show how to apply concepts from the field of reliable computing in order to build a framework for management of uncertainty in volume rendering, with the result being a self validating computational model to compute a posteriori uncertainty bounds. We begin by adopting a coherent, unifying possibility-based representation of uncertainty that is able to capture the various forms of uncertainty that appear in visualization, including variability, imprecision, and fuzziness. Next, we extend the concept of the fuzzy transform in order to derive rules for accumulation and propagation of uncertainty. This representation and propagation of uncertainty together constitute an automated framework for management of uncertainty in visualization, which we then apply to volume rendering. The result, which we call fuzzy volume rendering, is an uncertainty-aware rendering algorithm able to produce more complete depictions of the volume data, thereby allowing more reliable conclusions and informed decisions. Finally, we compare approaches for self-validated computation in volume rendering, demonstrating that our chosen method has the ability to handle complex uncertainty while maintaining efficiency. PMID- 26357142 TI - Automatic Tuning of Spatially Varying Transfer Functions for Blood Vessel Visualization. AB - Computed Tomography Angiography (CTA) is commonly used in clinical routine for diagnosing vascular diseases. The procedure involves the injection of a contrast agent into the blood stream to increase the contrast between the blood vessels and the surrounding tissue in the image data. CTA is often visualized with Direct Volume Rendering (DVR) where the enhanced image contrast is important for the construction of Transfer Functions (TFs). For increased efficiency, clinical routine heavily relies on preset TFs to simplify the creation of such visualizations for a physician. In practice, however, TF presets often do not yield optimal images due to variations in mixture concentration of contrast agent in the blood stream. In this paper we propose an automatic, optimization-based method that shifts TF presets to account for general deviations and local variations of the intensity of contrast enhanced blood vessels. Some of the advantages of this method are the following. It computationally automates large parts of a process that is currently performed manually. It performs the TF shift locally and can thus optimize larger portions of the image than is possible with manual interaction. The method is based on a well known vesselness descriptor in the definition of the optimization criterion. The performance of the method is illustrated by clinically relevant CT angiography datasets displaying both improved structural overviews of vessel trees and improved adaption to local variations of contrast concentration. PMID- 26357143 TI - Hierarchical Exploration of Volumes Using Multilevel Segmentation of the Intensity-Gradient Histograms. AB - Visual exploration of volumetric datasets to discover the embedded features and spatial structures is a challenging and tedious task. In this paper we present a semi-automatic approach to this problem that works by visually segmenting the intensity-gradient 2D histogram of a volumetric dataset into an exploration hierarchy. Our approach mimics user exploration behavior by analyzing the histogram with the normalized-cut multilevel segmentation technique. Unlike previous work in this area, our technique segments the histogram into a reasonable set of intuitive components that are mutually exclusive and collectively exhaustive. We use information-theoretic measures of the volumetric data segments to guide the exploration. This provides a data-driven coarse-to fine hierarchy for a user to interactively navigate the volume in a meaningful manner. PMID- 26357144 TI - Historygrams: Enabling Interactive Global Illumination in Direct Volume Rendering using Photon Mapping. AB - In this paper, we enable interactive volumetric global illumination by extending photon mapping techniques to handle interactive transfer function (TF) and material editing in the context of volume rendering. We propose novel algorithms and data structures for finding and evaluating parts of a scene affected by these parameter changes, and thus support efficient updates of the photon map. In direct volume rendering (DVR) the ability to explore volume data using parameter changes, such as editable TFs, is of key importance. Advanced global illumination techniques are in most cases computationally too expensive, as they prevent the desired interactivity. Our technique decreases the amount of computation caused by parameter changes, by introducing Historygrams which allow us to efficiently reuse previously computed photon media interactions. Along the viewing rays, we utilize properties of the light transport equations to subdivide a view-ray into segments and independently update them when invalid. Unlike segments of a view ray, photon scattering events within the volumetric medium needs to be sequentially updated. Using our Historygram approach, we can identify the first invalid photon interaction caused by a property change, and thus reuse all valid photon interactions. Combining these two novel concepts, supports interactive editing of parameters when using volumetric photon mapping in the context of DVR. As a consequence, we can handle arbitrarily shaped and positioned light sources, arbitrary phase functions, bidirectional reflectance distribution functions and multiple scattering which has previously not been possible in interactive DVR. PMID- 26357145 TI - Structure-Aware Lighting Design for Volume Visualization. AB - Lighting design is a complex, but fundamental, problem in many fields. In volume visualization, direct volume rendering generates an informative image without external lighting, as each voxel itself emits radiance. However, external lighting further improves the shape and detail perception of features, and it also determines the effectiveness of the communication of feature information. The human visual system is highly effective in extracting structural information from images, and to assist it further, this paper presents an approach to structure-aware automatic lighting design by measuring the structural changes between the images with and without external lighting. Given a transfer function and a viewpoint, the optimal lighting parameters are those that provide the greatest enhancement to structural information - the shape and detail information of features are conveyed most clearly by the optimal lighting parameters. Besides lighting goodness, the proposed metric can also be used to evaluate lighting similarity and stability between two sets of lighting parameters. Lighting similarity can be used to optimize the selection of multiple light sources so that different light sources can reveal distinct structural information. Our experiments with several volume data sets demonstrate the effectiveness of the structure-aware lighting design approach. It is well suited to use by novices as it requires little technical understanding of the rendering parameters associated with direct volume rendering. PMID- 26357146 TI - Multivariate Data Analysis Using Persistence-Based Filtering and Topological Signatures. AB - The extraction of significant structures in arbitrary high-dimensional data sets is a challenging task. Moreover, classifying data points as noise in order to reduce a data set bears special relevance for many application domains. Standard methods such as clustering serve to reduce problem complexity by providing the user with classes of similar entities. However, they usually do not highlight relations between different entities and require a stopping criterion, e.g. the number of clusters to be detected. In this paper, we present a visualization pipeline based on recent advancements in algebraic topology. More precisely, we employ methods from persistent homology that enable topological data analysis on high-dimensional data sets. Our pipeline inherently copes with noisy data and data sets of arbitrary dimensions. It extracts central structures of a data set in a hierarchical manner by using a persistence-based filtering algorithm that is theoretically well-founded. We furthermore introduce persistence rings, a novel visualization technique for a class of topological features-the persistence intervals-of large data sets. Persistence rings provide a unique topological signature of a data set, which helps in recognizing similarities. In addition, we provide interactive visualization techniques that assist the user in evaluating the parameter space of our method in order to extract relevant structures. We describe and evaluate our analysis pipeline by means of two very distinct classes of data sets: First, a class of synthetic data sets containing topological objects is employed to highlight the interaction capabilities of our method. Second, in order to affirm the utility of our technique, we analyse a class of high-dimensional real-world data sets arising from current research in cultural heritage. PMID- 26357147 TI - Surface-Based Structure Analysis and Visualization for Multifield Time-Varying Datasets. AB - This paper introduces a new feature analysis and visualization method for multifield datasets. Our approach applies a surface-centric model to characterize salient features and form an effective, schematic representation of the data. We propose a simple, geometrically motivated, multifield feature definition. This definition relies on an iterative algorithm that applies existing theory of skeleton derivation to fuse the structures from the constitutive fields into a coherent data description, while addressing noise and spurious details. This paper also presents a new method for non-rigid surface registration between the surfaces of consecutive time steps. This matching is used in conjunction with clustering to discover the interaction patterns between the different fields and their evolution over time. We document the unified visual analysis achieved by our method in the context of several multifield problems from large-scale time varying simulations. PMID- 26357148 TI - How Capacity Limits of Attention Influence Information Visualization Effectiveness. AB - In this paper, we explore how the capacity limits of attention influence the effectiveness of information visualizations. We conducted a series of experiments to test how visual feature type (color vs. motion), layout, and variety of visual elements impacted user performance. The experiments tested users' abilities to (1) determine if a specified target is on the screen, (2) detect an odd-ball, deviant target, different from the other visible objects, and (3) gain a qualitative overview by judging the number of unique categories on the screen. Our results show that the severe capacity limits of attention strongly modulate the effectiveness of information visualizations, particularly the ability to detect unexpected information. Keeping in mind these capacity limits, we conclude with a set of design guidelines which depend on a visualization's intended use. PMID- 26357149 TI - Different Strokes for Different Folks: Visual Presentation Design between Disciplines. AB - We present an ethnographic study of design differences in visual presentations between academic disciplines. Characterizing design conventions between users and data domains is an important step in developing hypotheses, tools, and design guidelines for information visualization. In this paper, disciplines are compared at a coarse scale between four groups of fields: social, natural, and formal sciences; and the humanities. Two commonplace presentation types were analyzed: electronic slideshows and whiteboard "chalk talks". We found design differences in slideshows using two methods - coding and comparing manually-selected features, like charts and diagrams, and an image-based analysis using PCA called eigenslides. In whiteboard talks with controlled topics, we observed design behaviors, including using representations and formalisms from a participant's own discipline, that suggest authors might benefit from novel assistive tools for designing presentations. Based on these findings, we discuss opportunities for visualization ethnography and human-centered authoring tools for visual information. PMID- 26357150 TI - Does an Eye Tracker Tell the Truth about Visualizations?: Findings while Investigating Visualizations for Decision Making. AB - For information visualization researchers, eye tracking has been a useful tool to investigate research participants' underlying cognitive processes by tracking their eye movements while they interact with visual techniques. We used an eye tracker to better understand why participants with a variant of a tabular visualization called 'SimulSort' outperformed ones with a conventional table and typical one-column sorting feature (i.e., Typical Sorting). The collected eye tracking data certainly shed light on the detailed cognitive processes of the participants; SimulSort helped with decision-making tasks by promoting efficient browsing behavior and compensatory decision-making strategies. However, more interestingly, we also found unexpected eye-tracking patterns with SimulSort. We investigated the cause of the unexpected patterns through a crowdsourcing-based study (i.e., Experiment 2), which elicited an important limitation of the eye tracking method: incapability of capturing peripheral vision. This particular result would be a caveat for other visualization researchers who plan to use an eye tracker in their studies. In addition, the method to use a testing stimulus (i.e., influential column) in Experiment 2 to verify the existence of such limitations would be useful for researchers who would like to verify their eye tracking results. PMID- 26357151 TI - Design Study Methodology: Reflections from the Trenches and the Stacks. AB - Design studies are an increasingly popular form of problem-driven visualization research, yet there is little guidance available about how to do them effectively. In this paper we reflect on our combined experience of conducting twenty-one design studies, as well as reading and reviewing many more, and on an extensive literature review of other field work methods and methodologies. Based on this foundation we provide definitions, propose a methodological framework, and provide practical guidance for conducting design studies. We define a design study as a project in which visualization researchers analyze a specific real world problem faced by domain experts, design a visualization system that supports solving this problem, validate the design, and reflect about lessons learned in order to refine visualization design guidelines. We characterize two axes - a task clarity axis from fuzzy to crisp and an information location axis from the domain expert's head to the computer - and use these axes to reason about design study contributions, their suitability, and uniqueness from other approaches. The proposed methodological framework consists of 9 stages: learn, winnow, cast, discover, design, implement, deploy, reflect, and write. For each stage we provide practical guidance and outline potential pitfalls. We also conducted an extensive literature survey of related methodological approaches that involve a significant amount of qualitative field work, and compare design study methodology to that of ethnography, grounded theory, and action research. PMID- 26357152 TI - Graphical Tests for Power Comparison of Competing Designs. AB - Lineups have been established as tools for visual testing similar to standard statistical inference tests, allowing us to evaluate the validity of graphical findings in an objective manner. In simulation studies lineups have been shown as being efficient: the power of visual tests is comparable to classical tests while being much less stringent in terms of distributional assumptions made. This makes lineups versatile, yet powerful, tools in situations where conditions for regular statistical tests are not or cannot be met. In this paper we introduce lineups as a tool for evaluating the power of competing graphical designs. We highlight some of the theoretical properties and then show results from two studies evaluating competing designs: both studies are designed to go to the limits of our perceptual abilities to highlight differences between designs. We use both accuracy and speed of evaluation as measures of a successful design. The first study compares the choice of coordinate system: polar versus cartesian coordinates. The results show strong support in favor of cartesian coordinates in finding fast and accurate answers to spotting patterns. The second study is aimed at finding shift differences between distributions. Both studies are motivated by data problems that we have recently encountered, and explore using simulated data to evaluate the plot designs under controlled conditions. Amazon Mechanical Turk (MTurk) is used to conduct the studies. The lineups provide an effective mechanism for objectively evaluating plot designs. PMID- 26357153 TI - A User Study on Curved Edges in Graph Visualization. AB - Recently there has been increasing research interest in displaying graphs with curved edges to produce more readable visualizations. While there are several automatic techniques, little has been done to evaluate their effectiveness empirically. In this paper we present two experiments studying the impact of edge curvature on graph readability. The goal is to understand the advantages and disadvantages of using curved edges for common graph tasks compared to straight line segments, which are the conventional choice for showing edges in node-link diagrams. We included several edge variations: straight edges, edges with different curvature levels, and mixed straight and curved edges. During the experiments, participants were asked to complete network tasks including determination of connectivity, shortest path, node degree, and common neighbors. We also asked the participants to provide subjective ratings of the aesthetics of different edge types. The results show significant performance differences between the straight and curved edges and clear distinctions between variations of curved edges. PMID- 26357154 TI - Compressed Adjacency Matrices: Untangling Gene Regulatory Networks. AB - We present a novel technique-Compressed Adjacency Matrices-for visualizing gene regulatory networks. These directed networks have strong structural characteristics: out-degrees with a scale-free distribution, in-degrees bound by a low maximum, and few and small cycles. Standard visualization techniques, such as node-link diagrams and adjacency matrices, are impeded by these network characteristics. The scale-free distribution of out-degrees causes a high number of intersecting edges in node-link diagrams. Adjacency matrices become space inefficient due to the low in-degrees and the resulting sparse network. Compressed adjacency matrices, however, exploit these structural characteristics. By cutting open and rearranging an adjacency matrix, we achieve a compact and neatly-arranged visualization. Compressed adjacency matrices allow for easy detection of subnetworks with a specific structure, so-called motifs, which provide important knowledge about gene regulatory networks to domain experts. We summarize motifs commonly referred to in the literature, and relate them to network analysis tasks common to the visualization domain. We show that a user can easily find the important motifs in compressed adjacency matrices, and that this is hard in standard adjacency matrix and node-link diagrams. We also demonstrate that interaction techniques for standard adjacency matrices can be used for our compressed variant. These techniques include rearrangement clustering, highlighting, and filtering. PMID- 26357155 TI - Visualizing Network Traffic to Understand the Performance of Massively Parallel Simulations. AB - The performance of massively parallel applications is often heavily impacted by the cost of communication among compute nodes. However, determining how to best use the network is a formidable task, made challenging by the ever increasing size and complexity of modern supercomputers. This paper applies visualization techniques to aid parallel application developers in understanding the network activity by enabling a detailed exploration of the flow of packets through the hardware interconnect. In order to visualize this large and complex data, we employ two linked views of the hardware network. The first is a 2D view, that represents the network structure as one of several simplified planar projections. This view is designed to allow a user to easily identify trends and patterns in the network traffic. The second is a 3D view that augments the 2D view by preserving the physical network topology and providing a context that is familiar to the application developers. Using the massively parallel multi-physics code pF3D as a case study, we demonstrate that our tool provides valuable insight that we use to explain and optimize pF3D's performance on an IBM Blue Gene/P system. PMID- 26357156 TI - Memorability of Visual Features in Network Diagrams. AB - We investigate the cognitive impact of various layout features-symmetry, alignment, collinearity, axis alignment and orthogonality - on the recall of network diagrams (graphs). This provides insight into how people internalize these diagrams and what features should or shouldn't be utilised when designing static and interactive network-based visualisations. Participants were asked to study, remember, and draw a series of small network diagrams, each drawn to emphasise a particular visual feature. The visual features were based on existing theories of perception, and the task enabled visual processing at the visceral level only. Our results strongly support the importance of visual features such as symmetry, collinearity and orthogonality, while not showing any significant impact for node-alignment or parallel edges. PMID- 26357157 TI - Interactive Level-of-Detail Rendering of Large Graphs. AB - We propose a technique that allows straight-line graph drawings to be rendered interactively with adjustable level of detail. The approach consists of a novel combination of edge cumulation with density-based node aggregation and is designed to exploit common graphics hardware for speed. It operates directly on graph data and does not require precomputed hierarchies or meshes. As proof of concept, we present an implementation that scales to graphs with millions of nodes and edges, and discuss several example applications. PMID- 26357158 TI - Visual Semiotics & Uncertainty Visualization: An Empirical Study. AB - This paper presents two linked empirical studies focused on uncertainty visualization. The experiments are framed from two conceptual perspectives. First, a typology of uncertainty is used to delineate kinds of uncertainty matched with space, time, and attribute components of data. Second, concepts from visual semiotics are applied to characterize the kind of visual signification that is appropriate for representing those different categories of uncertainty. This framework guided the two experiments reported here. The first addresses representation intuitiveness, considering both visual variables and iconicity of representation. The second addresses relative performance of the most intuitive abstract and iconic representations of uncertainty on a map reading task. Combined results suggest initial guidelines for representing uncertainty and discussion focuses on practical applicability of results. PMID- 26357159 TI - Comparing Clusterings Using Bertin's Idea. AB - Classifying a set of objects into clusters can be done in numerous ways, producing different results. They can be visually compared using contingency tables, mosaicplots, fluctuation diagrams, tableplots, (modified) parallel coordinates plots, Parallel Sets plots or circos diagrams. Unfortunately the interpretability of all these graphical displays decreases rapidly with the numbers of categories and clusterings. In his famous book A Semiology of Graphics Bertin writes "the discovery of an ordered concept appears as the ultimate point in logical simplification since it permits reducing to a single instant the assimilation of series which previously required many instants of study". Or in more everyday language, if you use good orderings you can see results immediately that with other orderings might take a lot of effort. This is also related to the idea of effect ordering, that data should be organised to reflect the effect you want to observe. This paper presents an efficient algorithm based on Bertin's idea and concepts related to Kendall's t, which finds informative joint orders for two or more nominal classification variables. We also show how these orderings improve the various displays and how groups of corresponding categories can be detected using a top-down partitioning algorithm. Different clusterings based on data on the environmental performance of cars sold in Germany are used for illustration. All presented methods are available in the R package extracat which is used to compute the optimized orderings for the example dataset. PMID- 26357160 TI - Perception of Visual Variables on Tiled Wall-Sized Displays for Information Visualization Applications. AB - We present the results of two user studies on the perception of visual variables on tiled high-resolution wall-sized displays. We contribute an understanding of, and indicators predicting how, large variations in viewing distances and viewing angles affect the accurate perception of angles, areas, and lengths. Our work, thus, helps visualization researchers with design considerations on how to create effective visualizations for these spaces. The first study showed that perception accuracy was impacted most when viewers were close to the wall but differently for each variable (Angle, Area, Length). Our second study examined the effect of perception when participants could move freely compared to when they had a static viewpoint. We found that a far but static viewpoint was as accurate but less time consuming than one that included free motion. Based on our findings, we recommend encouraging viewers to stand further back from the display when conducting perception estimation tasks. If tasks need to be conducted close to the wall display, important information should be placed directly in front of the viewer or above, and viewers should be provided with an estimation of the distortion effects predicted by our work-or encouraged to physically navigate the wall in specific ways to reduce judgement error. PMID- 26357161 TI - Visualizing Flow of Uncertainty through Analytical Processes. AB - Uncertainty can arise in any stage of a visual analytics process, especially in data-intensive applications with a sequence of data transformations. Additionally, throughout the process of multidimensional, multivariate data analysis, uncertainty due to data transformation and integration may split, merge, increase, or decrease. This dynamic characteristic along with other features of uncertainty pose a great challenge to effective uncertainty-aware visualization. This paper presents a new framework for modeling uncertainty and characterizing the evolution of the uncertainty information through analytical processes. Based on the framework, we have designed a visual metaphor called uncertainty flow to visually and intuitively summarize how uncertainty information propagates over the whole analysis pipeline. Our system allows analysts to interact with and analyze the uncertainty information at different levels of detail. Three experiments were conducted to demonstrate the effectiveness and intuitiveness of our design. PMID- 26357162 TI - Assessing the Effect of Visualizations on Bayesian Reasoning through Crowdsourcing. AB - People have difficulty understanding statistical information and are unaware of their wrong judgments, particularly in Bayesian reasoning. Psychology studies suggest that the way Bayesian problems are represented can impact comprehension, but few visual designs have been evaluated and only populations with a specific background have been involved. In this study, a textual and six visual representations for three classic problems were compared using a diverse subject pool through crowdsourcing. Visualizations included area-proportional Euler diagrams, glyph representations, and hybrid diagrams combining both. Our study failed to replicate previous findings in that subjects' accuracy was remarkably lower and visualizations exhibited no measurable benefit. A second experiment confirmed that simply adding a visualization to a textual Bayesian problem is of little help, even when the text refers to the visualization, but suggests that visualizations are more effective when the text is given without numerical values. We discuss our findings and the need for more such experiments to be carried out on heterogeneous populations of non-experts. PMID- 26357163 TI - Organizing Search Results with a Reference Map. AB - We propose a method to highlight query hits in hierarchically clustered collections of interrelated items such as digital libraries or knowledge bases. The method is based on the idea that organizing search results similarly to their arrangement on a fixed reference map facilitates orientation and assessment by preserving a user's mental map. Here, the reference map is built from an MDS layout of the items in a Voronoi treemap representing their hierarchical clustering, and we use techniques from dynamic graph layout to align query results with the map. The approach is illustrated on an archive of newspaper articles. PMID- 26357164 TI - Spatial Text Visualization Using Automatic Typographic Maps. AB - We present a method for automatically building typographic maps that merge text and spatial data into a visual representation where text alone forms the graphical features. We further show how to use this approach to visualize spatial data such as traffic density, crime rate, or demographic data. The technique accepts a vector representation of a geographic map and spatializes the textual labels in the space onto polylines and polygons based on user-defined visual attributes and constraints. Our sample implementation runs as a Web service, spatializing shape files from the OpenStreetMap project into typographic maps for any region. PMID- 26357165 TI - Stacking-Based Visualization of Trajectory Attribute Data. AB - Visualizing trajectory attribute data is challenging because it involves showing the trajectories in their spatio-temporal context as well as the attribute values associated with the individual points of trajectories. Previous work on trajectory visualization addresses selected aspects of this problem, but not all of them. We present a novel approach to visualizing trajectory attribute data. Our solution covers space, time, and attribute values. Based on an analysis of relevant visualization tasks, we designed the visualization solution around the principle of stacking trajectory bands. The core of our approach is a hybrid 2D/3D display. A 2D map serves as a reference for the spatial context, and the trajectories are visualized as stacked 3D trajectory bands along which attribute values are encoded by color. Time is integrated through appropriate ordering of bands and through a dynamic query mechanism that feeds temporally aggregated information to a circular time display. An additional 2D time graph shows temporal information in full detail by stacking 2D trajectory bands. Our solution is equipped with analytical and interactive mechanisms for selecting and ordering of trajectories, and adjusting the color mapping, as well as coordinated highlighting and dedicated 3D navigation. We demonstrate the usefulness of our novel visualization by three examples related to radiation surveillance, traffic analysis, and maritime navigation. User feedback obtained in a small experiment indicates that our hybrid 2D/3D solution can be operated quite well. PMID- 26357166 TI - Adaptive Composite Map Projections. AB - All major web mapping services use the web Mercator projection. This is a poor choice for maps of the entire globe or areas of the size of continents or larger countries because the Mercator projection shows medium and higher latitudes with extreme areal distortion and provides an erroneous impression of distances and relative areas. The web Mercator projection is also not able to show the entire globe, as polar latitudes cannot be mapped. When selecting an alternative projection for information visualization, rivaling factors have to be taken into account, such as map scale, the geographic area shown, the map's height-to-width ratio, and the type of cartographic visualization. It is impossible for a single map projection to meet the requirements for all these factors. The proposed composite map projection combines several projections that are recommended in cartographic literature and seamlessly morphs map space as the user changes map scale or the geographic region displayed. The composite projection adapts the map's geometry to scale, to the map's height-to-width ratio, and to the central latitude of the displayed area by replacing projections and adjusting their parameters. The composite projection shows the entire globe including poles; it portrays continents or larger countries with less distortion (optionally without areal distortion); and it can morph to the web Mercator projection for maps showing small regions. PMID- 26357167 TI - Algorithms for Labeling Focus Regions. AB - In this paper, we investigate the problem of labeling point sites in focus regions of maps or diagrams. This problem occurs, for example, when the user of a mapping service wants to see the names of restaurants or other POIs in a crowded downtown area but keep the overview over a larger area. Our approach is to place the labels at the boundary of the focus region and connect each site with its label by a linear connection, which is called a leader. In this way, we move labels from the focus region to the less valuable context region surrounding it. In order to make the leader layout well readable, we present algorithms that rule out crossings between leaders and optimize other characteristics such as total leader length and distance between labels. This yields a new variant of the boundary labeling problem, which has been studied in the literature. Other than in traditional boundary labeling, where leaders are usually schematized polylines, we focus on leaders that are either straight-line segments or Bezier curves. Further, we present algorithms that, given the sites, find a position of the focus region that optimizes the above characteristics. We also consider a variant of the problem where we have more sites than space for labels. In this situation, we assume that the sites are prioritized by the user. Alternatively, we take a new facility-location perspective which yields a clustering of the sites. We label one representative of each cluster. If the user wishes, we apply our approach to the sites within a cluster, giving details on demand. PMID- 26357168 TI - Capturing the Design Space of Sequential Space-Filling Layouts. AB - We characterize the design space of the algorithms that sequentially tile a rectangular area with smaller, fixed-surface, rectangles. This space consist of five independent dimensions: Order, Size, Score, Recurse and Phrase. Each of these dimensions describe a particular aspect of such layout tasks. This class of layouts is interesting, because, beyond encompassing simple grids, tables and trees, it also includes all kinds of treemaps involving the placement of rectangles. For instance, Slice and dice, Squarified, Strip and Pivot layouts are various points in this five dimensional space. Many classic statistics visualizations, such as 100% stacked bar charts, mosaic plots and dimensional stacking, are also instances of this class. A few new and potentially interesting points in this space are introduced, such as spiral treemaps and variations on the strip layout. The core algorithm is implemented as a JavaScript prototype that can be used as a layout component in a variety of InfoViz toolkits. PMID- 26357169 TI - Taxonomy-Based Glyph Design—with a Case Study on Visualizing Workflows of Biological Experiments. AB - Glyph-based visualization can offer elegant and concise presentation of multivariate information while enhancing speed and ease in visual search experienced by users. As with icon designs, glyphs are usually created based on the designers' experience and intuition, often in a spontaneous manner. Such a process does not scale well with the requirements of applications where a large number of concepts are to be encoded using glyphs. To alleviate such limitations, we propose a new systematic process for glyph design by exploring the parallel between the hierarchy of concept categorization and the ordering of discriminative capacity of visual channels. We examine the feasibility of this approach in an application where there is a pressing need for an efficient and effective means to visualize workflows of biological experiments. By processing thousands of workflow records in a public archive of biological experiments, we demonstrate that a cost-effective glyph design can be obtained by following a process of formulating a taxonomy with the aid of computation, identifying visual channels hierarchically, and defining application-specific abstraction and metaphors. PMID- 26357170 TI - An Empirical Model of Slope Ratio Comparisons. AB - Comparing slopes is a fundamental graph reading task and the aspect ratio chosen for a plot influences how easy these comparisons are to make. According to Banking to 45 degrees , a classic design guideline first proposed and studied by Cleveland et al., aspect ratios that center slopes around 45 degrees minimize errors in visual judgments of slope ratios. This paper revisits this earlier work. Through exploratory pilot studies that expand Cleveland et al.'s experimental design, we develop an empirical model of slope ratio estimation that fits more extreme slope ratio judgments and two common slope ratio estimation strategies. We then run two experiments to validate our model. In the first, we show that our model fits more generally than the one proposed by Cleveland et al. and we find that, in general, slope ratio errors are not minimized around 45 degrees . In the second experiment, we explore a novel hypothesis raised by our model: that visible baselines can substantially mitigate errors made in slope judgments. We conclude with an application of our model to aspect ratio selection. PMID- 26357171 TI - Representative Factor Generation for the Interactive Visual Analysis of High Dimensional Data. AB - Datasets with a large number of dimensions per data item (hundreds or more) are challenging both for computational and visual analysis. Moreover, these dimensions have different characteristics and relations that result in sub-groups and/or hierarchies over the set of dimensions. Such structures lead to heterogeneity within the dimensions. Although the consideration of these structures is crucial for the analysis, most of the available analysis methods discard the heterogeneous relations among the dimensions. In this paper, we introduce the construction and utilization of representative factors for the interactive visual analysis of structures in high-dimensional datasets. First, we present a selection of methods to investigate the sub-groups in the dimension set and associate representative factors with those groups of dimensions. Second, we introduce how these factors are included in the interactive visual analysis cycle together with the original dimensions. We then provide the steps of an analytical procedure that iteratively analyzes the datasets through the use of representative factors. We discuss how our methods improve the reliability and interpretability of the analysis process by enabling more informed selections of computational tools. Finally, we demonstrate our techniques on the analysis of brain imaging study results that are performed over a large group of subjects. PMID- 26357172 TI - Graphical Overlays: Using Layered Elements to Aid Chart Reading. AB - Reading a visualization can involve a number of tasks such as extracting, comparing or aggregating numerical values. Yet, most of the charts that are published in newspapers, reports, books, and on the Web only support a subset of these tasks. In this paper we introduce graphical overlays-visual elements that are layered onto charts to facilitate a larger set of chart reading tasks. These overlays directly support the lower-level perceptual and cognitive processes that viewers must perform to read a chart. We identify five main types of overlays that support these processes; the overlays can provide (1) reference structures such as gridlines, (2) highlights such as outlines around important marks, (3) redundant encodings such as numerical data labels, (4) summary statistics such as the mean or max and (5) annotations such as descriptive text for context. We then present an automated system that applies user-chosen graphical overlays to existing chart bitmaps. Our approach is based on the insight that generating most of these graphical overlays only requires knowing the properties of the visual marks and axes that encode the data, but does not require access to the underlying data values. Thus, our system analyzes the chart bitmap to extract only the properties necessary to generate the desired overlay. We also discuss techniques for generating interactive overlays that provide additional controls to viewers. We demonstrate several examples of each overlay type for bar, pie and line charts. PMID- 26357173 TI - Facilitating Discourse Analysis with Interactive Visualization. AB - A discourse parser is a natural language processing system which can represent the organization of a document based on a rhetorical structure tree-one of the key data structures enabling applications such as text summarization, question answering and dialogue generation. Computational linguistics researchers currently rely on manually exploring and comparing the discourse structures to get intuitions for improving parsing algorithms. In this paper, we present DAViewer, an interactive visualization system for assisting computational linguistics researchers to explore, compare, evaluate and annotate the results of discourse parsers. An iterative user-centered design process with domain experts was conducted in the development of DAViewer. We report the results of an informal formative study of the system to better understand how the proposed visualization and interaction techniques are used in the real research environment. PMID- 26357174 TI - Whisper: Tracing the Spatiotemporal Process of Information Diffusion in Real Time. AB - When and where is an idea dispersed? Social media, like Twitter, has been increasingly used for exchanging information, opinions and emotions about events that are happening across the world. Here we propose a novel visualization design, "Whisper", for tracing the process of information diffusion in social media in real time. Our design highlights three major characteristics of diffusion processes in social media: the temporal trend, social-spatial extent, and community response of a topic of interest. Such social, spatiotemporal processes are conveyed based on a sunflower metaphor whose seeds are often dispersed far away. In Whisper, we summarize the collective responses of communities on a given topic based on how tweets were retweeted by groups of users, through representing the sentiments extracted from the tweets, and tracing the pathways of retweets on a spatial hierarchical layout. We use an efficient flux line-drawing algorithm to trace multiple pathways so the temporal and spatial patterns can be identified even for a bursty event. A focused diffusion series highlights key roles such as opinion leaders in the diffusion process. We demonstrate how our design facilitates the understanding of when and where a piece of information is dispersed and what are the social responses of the crowd, for large-scale events including political campaigns and natural disasters. Initial feedback from domain experts suggests promising use for today's information consumption and dispersion in the wild. PMID- 26357175 TI - Exploring Flow, Factors, and Outcomes of Temporal Event Sequences with the Outflow Visualization. AB - Event sequence data is common in many domains, ranging from electronic medical records (EMRs) to sports events. Moreover, such sequences often result in measurable outcomes (e.g., life or death, win or loss). Collections of event sequences can be aggregated together to form event progression pathways. These pathways can then be connected with outcomes to model how alternative chains of events may lead to different results. This paper describes the Outflow visualization technique, designed to (1) aggregate multiple event sequences, (2) display the aggregate pathways through different event states with timing and cardinality, (3) summarize the pathways' corresponding outcomes, and (4) allow users to explore external factors that correlate with specific pathway state transitions. Results from a user study with twelve participants show that users were able to learn how to use Outflow easily with limited training and perform a range of tasks both accurately and rapidly. PMID- 26357176 TI - RankExplorer: Visualization of Ranking Changes in Large Time Series Data. AB - For many applications involving time series data, people are often interested in the changes of item values over time as well as their ranking changes. For example, people search many words via search engines like Google and Bing every day. Analysts are interested in both the absolute searching number for each word as well as their relative rankings. Both sets of statistics may change over time. For very large time series data with thousands of items, how to visually present ranking changes is an interesting challenge. In this paper, we propose RankExplorer, a novel visualization method based on ThemeRiver to reveal the ranking changes. Our method consists of four major components: 1) a segmentation method which partitions a large set of time series curves into a manageable number of ranking categories; 2) an extended ThemeRiver view with embedded color bars and changing glyphs to show the evolution of aggregation values related to each ranking category over time as well as the content changes in each ranking category; 3) a trend curve to show the degree of ranking changes over time; 4) rich user interactions to support interactive exploration of ranking changes. We have applied our method to some real time series data and the case studies demonstrate that our method can reveal the underlying patterns related to ranking changes which might otherwise be obscured in traditional visualizations. PMID- 26357177 TI - Design Considerations for Optimizing Storyline Visualizations. AB - Storyline visualization is a technique used to depict the temporal dynamics of social interactions. This visualization technique was first introduced as a hand drawn illustration in XKCD's "Movie Narrative Charts" [21]. If properly constructed, the visualization can convey both global trends and local interactions in the data. However, previous methods for automating storyline visualizations are overly simple, failing to achieve some of the essential principles practiced by professional illustrators. This paper presents a set of design considerations for generating aesthetically pleasing and legible storyline visualizations. Our layout algorithm is based on evolutionary computation, allowing us to effectively incorporate multiple objective functions. We show that the resulting visualizations have significantly improved aesthetics and legibility compared to existing techniques. PMID- 26357178 TI - Beyond Mouse and Keyboard: Expanding Design Considerations for Information Visualization Interactions. AB - The importance of interaction to Information Visualization (InfoVis) and, in particular, of the interplay between interactivity and cognition is widely recognized [12, 15, 32, 55, 70]. This interplay, combined with the demands from increasingly large and complex datasets, is driving the increased significance of interaction in InfoVis. In parallel, there have been rapid advances in many facets of interaction technologies. However, InfoVis interactions have yet to take full advantage of these new possibilities in interaction technologies, as they largely still employ the traditional desktop, mouse, and keyboard setup of WIMP (Windows, Icons, Menus, and a Pointer) interfaces. In this paper, we reflect more broadly about the role of more "natural" interactions for InfoVis and provide opportunities for future research. We discuss and relate general HCI interaction models to existing InfoVis interaction classifications by looking at interactions from a novel angle, taking into account the entire spectrum of interactions. Our discussion of InfoVis-specific interaction design considerations helps us identify a series of underexplored attributes of interaction that can lead to new, more "natural," interaction techniques for InfoVis. PMID- 26357179 TI - Intelligent Graph Layout Using Many Users' Input. AB - In this paper, we propose a new strategy for graph drawing utilizing layouts of many sub-graphs supplied by a large group of people in a crowd sourcing manner. We developed an algorithm based on Laplacian constrained distance embedding to merge subgraphs submitted by different users, while attempting to maintain the topological information of the individual input layouts. To facilitate collection of layouts from many people, a light-weight interactive system has been designed to enable convenient dynamic viewing, modification and traversing between layouts. Compared with other existing graph layout algorithms, our approach can achieve more aesthetic and meaningful layouts with high user preference. PMID- 26357180 TI - PivotPaths: Strolling through Faceted Information Spaces. AB - We present PivotPaths, an interactive visualization for exploring faceted information resources. During both work and leisure, we increasingly interact with information spaces that contain multiple facets and relations, such as authors, keywords, and citations of academic publications, or actors and genres of movies. To navigate these interlinked resources today, one typically selects items from facet lists resulting in abrupt changes from one subset of data to another. While filtering is useful to retrieve results matching specific criteria, it can be difficult to see how facets and items relate and to comprehend the effect of filter operations. In contrast, the PivotPaths interface exposes faceted relations as visual paths in arrangements that invite the viewer to 'take a stroll' through an information space. PivotPaths supports pivot operations as lightweight interaction techniques that trigger gradual transitions between views. We designed the interface to allow for casual traversal of large collections in an aesthetically pleasing manner that encourages exploration and serendipitous discoveries. This paper shares the findings from our iterative design-and-evaluation process that included semi-structured interviews and a two week deployment of PivotPaths applied to a large database of academic publications. PMID- 26357181 TI - Interaction Support for Visual Comparison Inspired by Natural Behavior. AB - Visual comparison is an intrinsic part of interactive data exploration and analysis. The literature provides a large body of existing solutions that help users accomplish comparison tasks. These solutions are mostly of visual nature and custom-made for specific data. We ask the question if a more general support is possible by focusing on the interaction aspect of comparison tasks. As an answer to this question, we propose a novel interaction concept that is inspired by real-world behavior of people comparing information printed on paper. In line with real-world interaction, our approach supports users (1) in interactively specifying pieces of graphical information to be compared, (2) in flexibly arranging these pieces on the screen, and (3) in performing the actual comparison of side-by-side and overlapping arrangements of the graphical information. Complementary visual cues and add-ons further assist users in carrying out comparison tasks. Our concept and the integrated interaction techniques are generally applicable and can be coupled with different visualization techniques. We implemented an interactive prototype and conducted a qualitative user study to assess the concept's usefulness in the context of three different visualization techniques. The obtained feedback indicates that our interaction techniques mimic the natural behavior quite well, can be learned quickly, and are easy to apply to visual comparison tasks. PMID- 26357182 TI - RelEx: Visualization for Actively Changing Overlay Network Specifications. AB - We present a network visualization design study focused on supporting automotive engineers who need to specify and optimize traffic patterns for in-car communication networks. The task and data abstractions that we derived support actively making changes to an overlay network, where logical communication specifications must be mapped to an underlying physical network. These abstractions are very different from the dominant use case in visual network analysis, namely identifying clusters and central nodes, that stems from the domain of social network analysis. Our visualization tool RelEx was created and iteratively refined through a full user-centered design process that included a full problem characterization phase before tool design began, paper prototyping, iterative refinement in close collaboration with expert users for formative evaluation, deployment in the field with real analysts using their own data, usability testing with non-expert users, and summative evaluation at the end of the deployment. In the summative post-deployment study, which entailed domain experts using the tool over several weeks in their daily practice, we documented many examples where the use of RelEx simplified or sped up their work compared to previous practices. PMID- 26357183 TI - Evaluating the Effect of Style in Information Visualization. AB - This paper reports on a between-subject, comparative online study of three information visualization demonstrators that each displayed the same dataset by way of an identical scatterplot technique, yet were different in style in terms of visual and interactive embellishment. We validated stylistic adherence and integrity through a separate experiment in which a small cohort of participants assigned our three demonstrators to predefined groups of stylistic examples, after which they described the styles with their own words. From the online study, we discovered significant differences in how participants execute specific interaction operations, and the types of insights that followed from them. However, in spite of significant differences in apparent usability, enjoyability and usefulness between the style demonstrators, no variation was found on the self-reported depth, expert-rated depth, confidence or difficulty of the resulting insights. Three different methods of insight analysis have been applied, revealing how style impacts the creation of insights, ranging from higher-level pattern seeking to a more reflective and interpretative engagement with content, which is what underlies the patterns. As this study only forms the first step in determining how the impact of style in information visualization could be best evaluated, we propose several guidelines and tips on how to gather, compare and categorize insights through an online evaluation study, particularly in terms of analyzing the concise, yet wide variety of insights and observations in a trustworthy and reproducable manner. PMID- 26357184 TI - Sketchy Rendering for Information Visualization. AB - We present and evaluate a framework for constructing sketchy style information visualizations that mimic data graphics drawn by hand. We provide an alternative renderer for the Processing graphics environment that redefines core drawing primitives including line, polygon and ellipse rendering. These primitives allow higher-level graphical features such as bar charts, line charts, treemaps and node-link diagrams to be drawn in a sketchy style with a specified degree of sketchiness. The framework is designed to be easily integrated into existing visualization implementations with minimal programming modification or design effort. We show examples of use for statistical graphics, conveying spatial imprecision and for enhancing aesthetic and narrative qualities of visualization. We evaluate user perception of sketchiness of areal features through a series of stimulus-response tests in order to assess users' ability to place sketchiness on a ratio scale, and to estimate area. Results suggest relative area judgment is compromised by sketchy rendering and that its influence is dependent on the shape being rendered. They show that degree of sketchiness may be judged on an ordinal scale but that its judgement varies strongly between individuals. We evaluate higher-level impacts of sketchiness through user testing of scenarios that encourage user engagement with data visualization and willingness to critique visualization design. Results suggest that where a visualization is clearly sketchy, engagement may be increased and that attitudes to participating in visualization annotation are more positive. The results of our work have implications for effective information visualization design that go beyond the traditional role of sketching as a tool for prototyping or its use for an indication of general uncertainty. PMID- 26357185 TI - An Empirical Study on Using Visual Embellishments in Visualization. AB - In written and spoken communications, figures of speech (e.g., metaphors and synecdoche) are often used as an aid to help convey abstract or less tangible concepts. However, the benefits of using rhetorical illustrations or embellishments in visualization have so far been inconclusive. In this work, we report an empirical study to evaluate hypotheses that visual embellishments may aid memorization, visual search and concept comprehension. One major departure from related experiments in the literature is that we make use of a dual-task methodology in our experiment. This design offers an abstraction of typical situations where viewers do not have their full attention focused on visualization (e.g., in meetings and lectures). The secondary task introduces "divided attention", and makes the effects of visual embellishments more observable. In addition, it also serves as additional masking in memory-based trials. The results of this study show that visual embellishments can help participants better remember the information depicted in visualization. On the other hand, visual embellishments can have a negative impact on the speed of visual search. The results show a complex pattern as to the benefits of visual embellishments in helping participants grasp key concepts from visualization. PMID- 26357186 TI - Evaluating Sketchiness as a Visual Variable for the Depiction of Qualitative Uncertainty. AB - We report on results of a series of user studies on the perception of four visual variables that are commonly used in the literature to depict uncertainty. To the best of our knowledge, we provide the first formal evaluation of the use of these variables to facilitate an easier reading of uncertainty in visualizations that rely on line graphical primitives. In addition to blur, dashing and grayscale, we investigate the use of 'sketchiness' as a visual variable because it conveys visual impreciseness that may be associated with data quality. Inspired by work in non-photorealistic rendering and by the features of hand-drawn lines, we generate line trajectories that resemble hand-drawn strokes of various levels of proficiency-ranging from child to adult strokes-where the amount of perturbations in the line corresponds to the level of uncertainty in the data. Our results show that sketchiness is a viable alternative for the visualization of uncertainty in lines and is as intuitive as blur; although people subjectively prefer dashing style over blur, grayscale and sketchiness. We discuss advantages and limitations of each technique and conclude with design considerations on how to deploy these visual variables to effectively depict various levels of uncertainty for line marks. PMID- 26357187 TI - Understanding Pen and Touch Interaction for Data Exploration on Interactive Whiteboards. AB - Current interfaces for common information visualizations such as bar graphs, line graphs, and scatterplots usually make use of the WIMP (Windows, Icons, Menus and a Pointer) interface paradigm with its frequently discussed problems of multiple levels of indirection via cascading menus, dialog boxes, and control panels. Recent advances in interface capabilities such as the availability of pen and touch interaction challenge us to re-think this and investigate more direct access to both the visualizations and the data they portray. We conducted a Wizard of Oz study to explore applying pen and touch interaction to the creation of information visualization interfaces on interactive whiteboards without implementing a plethora of recognizers. Our wizard acted as a robust and flexible pen and touch recognizer, giving participants maximum freedom in how they interacted with the system. Based on our qualitative analysis of the interactions our participants used, we discuss our insights about pen and touch interactions in the context of learnability and the interplay between pen and touch gestures. We conclude with suggestions for designing pen and touch enabled interactive visualization interfaces. PMID- 26357188 TI - The DeepTree Exhibit: Visualizing the Tree of Life to Facilitate Informal Learning. AB - In this paper, we present the DeepTree exhibit, a multi-user, multi-touch interactive visualization of the Tree of Life. We developed DeepTree to facilitate collaborative learning of evolutionary concepts. We will describe an iterative process in which a team of computer scientists, learning scientists, biologists, and museum curators worked together throughout design, development, and evaluation. We present the importance of designing the interactions and the visualization hand-in-hand in order to facilitate active learning. The outcome of this process is a fractal-based tree layout that reduces visual complexity while being able to capture all life on earth; a custom rendering and navigation engine that prioritizes visual appeal and smooth fly-through; and a multi-user interface that encourages collaborative exploration while offering guided discovery. We present an evaluation showing that the large dataset encouraged free exploration, triggers emotional responses, and facilitates visitor engagement and informal learning. PMID- 26357189 TI - Living Liquid: Design and Evaluation of an Exploratory Visualization Tool for Museum Visitors. AB - Interactive visualizations can allow science museum visitors to explore new worlds by seeing and interacting with scientific data. However, designing interactive visualizations for informal learning environments, such as museums, presents several challenges. First, visualizations must engage visitors on a personal level. Second, visitors often lack the background to interpret visualizations of scientific data. Third, visitors have very limited time at individual exhibits in museums. This paper examines these design considerations through the iterative development and evaluation of an interactive exhibit as a visualization tool that gives museumgoers access to scientific data generated and used by researchers. The exhibit prototype, Living Liquid, encourages visitors to ask and answer their own questions while exploring the time-varying global distribution of simulated marine microbes using a touchscreen interface. Iterative development proceeded through three rounds of formative evaluations using think-aloud protocols and interviews, each round informing a key visualization design decision: (1) what to visualize to initiate inquiry, (2) how to link data at the microscopic scale to global patterns, and (3) how to include additional data that allows visitors to pursue their own questions. Data from visitor evaluations suggests that, when designing visualizations for public audiences, one should (1) avoid distracting visitors from data that they should explore, (2) incorporate background information into the visualization, (3) favor understandability over scientific accuracy, and (4) layer data accessibility to structure inquiry. Lessons learned from this case study add to our growing understanding of how to use visualizations to actively engage learners with scientific data. PMID- 26357190 TI - Visualizing Student Histories Using Clustering and Composition. AB - While intuitive time-series visualizations exist for common datasets, student course history data is difficult to represent using traditional visualization techniques due its concurrent nature. A visual composition process is developed and applied to reveal trends across various groupings. By working closely with educators, analytic strategies and techniques are developed to leverage the visualization composition to reveal unknown trends in the data. Furthermore, clustering algorithms are developed to group common course-grade histories for further analysis. Lastly, variations of the composition process are implemented to reveal subtle differences in the underlying data. These analytic tools and techniques enabled educators to confirm expected trends and to discover new ones. PMID- 26357191 TI - SnapShot: Visualization to Propel Ice Hockey Analytics. AB - Sports analysts live in a world of dynamic games flattened into tables of numbers, divorced from the rinks, pitches, and courts where they were generated. Currently, these professional analysts use R, Stata, SAS, and other statistical software packages for uncovering insights from game data. Quantitative sports consultants seek a competitive advantage both for their clients and for themselves as analytics becomes increasingly valued by teams, clubs, and squads. In order for the information visualization community to support the members of this blossoming industry, it must recognize where and how visualization can enhance the existing analytical workflow. In this paper, we identify three primary stages of today's sports analyst's routine where visualization can be beneficially integrated: 1) exploring a dataspace; 2) sharing hypotheses with internal colleagues; and 3) communicating findings to stakeholders.Working closely with professional ice hockey analysts, we designed and built SnapShot, a system to integrate visualization into the hockey intelligence gathering process. SnapShot employs a variety of information visualization techniques to display shot data, yet given the importance of a specific hockey statistic, shot length, we introduce a technique, the radial heat map. Through a user study, we received encouraging feedback from several professional analysts, both independent consultants and professional team personnel. PMID- 26357192 TI - Scatter/Gather Clustering: Flexibly Incorporating User Feedback to Steer Clustering Results. AB - Significant effort has been devoted to designing clustering algorithms that are responsive to user feedback or that incorporate prior domain knowledge in the form of constraints. However, users desire more expressive forms of interaction to influence clustering outcomes. In our experiences working with diverse application scientists, we have identified an interaction style scatter/gather clustering that helps users iteratively restructure clustering results to meet their expectations. As the names indicate, scatter and gather are dual primitives that describe whether clusters in a current segmentation should be broken up further or, alternatively, brought back together. By combining scatter and gather operations in a single step, we support very expressive dynamic restructurings of data. Scatter/gather clustering is implemented using a nonlinear optimization framework that achieves both locality of clusters and satisfaction of user supplied constraints. We illustrate the use of our scatter/gather clustering approach in a visual analytic application to study baffle shapes in the bat biosonar (ears and nose) system. We demonstrate how domain experts are adept at supplying scatter/gather constraints, and how our framework incorporates these constraints effectively without requiring numerous instance-level constraints. PMID- 26357193 TI - Visual Classifier Training for Text Document Retrieval. AB - Performing exhaustive searches over a large number of text documents can be tedious, since it is very hard to formulate search queries or define filter criteria that capture an analyst's information need adequately. Classification through machine learning has the potential to improve search and filter tasks encompassing either complex or very specific information needs, individually. Unfortunately, analysts who are knowledgeable in their field are typically not machine learning specialists. Most classification methods, however, require a certain expertise regarding their parametrization to achieve good results. Supervised machine learning algorithms, in contrast, rely on labeled data, which can be provided by analysts. However, the effort for labeling can be very high, which shifts the problem from composing complex queries or defining accurate filters to another laborious task, in addition to the need for judging the trained classifier's quality. We therefore compare three approaches for interactive classifier training in a user study. All of the approaches are potential candidates for the integration into a larger retrieval system. They incorporate active learning to various degrees in order to reduce the labeling effort as well as to increase effectiveness. Two of them encompass interactive visualization for letting users explore the status of the classifier in context of the labeled documents, as well as for judging the quality of the classifier in iterative feedback loops. We see our work as a step towards introducing user controlled classification methods in addition to text search and filtering for increasing recall in analytics scenarios involving large corpora. PMID- 26357194 TI - Reinventing the Contingency Wheel: Scalable Visual Analytics of Large Categorical Data. AB - Contingency tables summarize the relations between categorical variables and arise in both scientific and business domains. Asymmetrically large two-way contingency tables pose a problem for common visualization methods. The Contingency Wheel has been recently proposed as an interactive visual method to explore and analyze such tables. However, the scalability and readability of this method are limited when dealing with large and dense tables. In this paper we present Contingency Wheel++, new visual analytics methods that overcome these major shortcomings: (1) regarding automated methods, a measure of association based on Pearson's residuals alleviates the bias of the raw residuals originally used, (2) regarding visualization methods, a frequency-based abstraction of the visual elements eliminates overlapping and makes analyzing both positive and negative associations possible, and (3) regarding the interactive exploration environment, a multi-level overview+detail interface enables exploring individual data items that are aggregated in the visualization or in the table using coordinated views. We illustrate the applicability of these new methods with a use case and show how they enable discovering and analyzing nontrivial patterns and associations in large categorical data. PMID- 26357195 TI - An Affordance-Based Framework for Human Computation and Human-Computer Collaboration. AB - Visual Analytics is "the science of analytical reasoning facilitated by visual interactive interfaces". The goal of this field is to develop tools and methodologies for approaching problems whose size and complexity render them intractable without the close coupling of both human and machine analysis. Researchers have explored this coupling in many venues: VAST, Vis, InfoVis, CHI, KDD, IUI, and more. While there have been myriad promising examples of human computer collaboration, there exists no common language for comparing systems or describing the benefits afforded by designing for such collaboration. We argue that this area would benefit significantly from consensus about the design attributes that define and distinguish existing techniques. In this work, we have reviewed 1,271 papers from many of the top-ranking conferences in visual analytics, human-computer interaction, and visualization. From these, we have identified 49 papers that are representative of the study of human-computer collaborative problem-solving, and provide a thorough overview of the current state-of-the-art. Our analysis has uncovered key patterns of design hinging on human and machine-intelligence affordances, and also indicates unexplored avenues in the study of this area. The results of this analysis provide a common framework for understanding these seemingly disparate branches of inquiry, which we hope will motivate future work in the field. PMID- 26357196 TI - Examining the Use of a Visual Analytics System for Sensemaking Tasks: Case Studies with Domain Experts. AB - While the formal evaluation of systems in visual analytics is still relatively uncommon, particularly rare are case studies of prolonged system use by domain analysts working with their own data. Conducting case studies can be challenging, but it can be a particularly effective way to examine whether visual analytics systems are truly helping expert users to accomplish their goals. We studied the use of a visual analytics system for sensemaking tasks on documents by six analysts from a variety of domains. We describe their application of the system along with the benefits, issues, and problems that we uncovered. Findings from the studies identify features that visual analytics systems should emphasize as well as missing capabilities that should be addressed. These findings inform design implications for future systems. PMID- 26357197 TI - Semantic Interaction for Sensemaking: Inferring Analytical Reasoning for Model Steering. AB - Visual analytic tools aim to support the cognitively demanding task of sensemaking. Their success often depends on the ability to leverage capabilities of mathematical models, visualization, and human intuition through flexible, usable, and expressive interactions. Spatially clustering data is one effective metaphor for users to explore similarity and relationships between information, adjusting the weighting of dimensions or characteristics of the dataset to observe the change in the spatial layout. Semantic interaction is an approach to user interaction in such spatializations that couples these parametric modifications of the clustering model with users' analytic operations on the data (e.g., direct document movement in the spatialization, highlighting text, search, etc.). In this paper, we present results of a user study exploring the ability of semantic interaction in a visual analytic prototype, ForceSPIRE, to support sensemaking. We found that semantic interaction captures the analytical reasoning of the user through keyword weighting, and aids the user in co-creating a spatialization based on the user's reasoning and intuition. PMID- 26357198 TI - Visual Analytics Methodology for Eye Movement Studies. AB - Eye movement analysis is gaining popularity as a tool for evaluation of visual displays and interfaces. However, the existing methods and tools for analyzing eye movements and scanpaths are limited in terms of the tasks they can support and effectiveness for large data and data with high variation. We have performed an extensive empirical evaluation of a broad range of visual analytics methods used in analysis of geographic movement data. The methods have been tested for the applicability to eye tracking data and the capability to extract useful knowledge about users' viewing behaviors. This allowed us to select the suitable methods and match them to possible analysis tasks they can support. The paper describes how the methods work in application to eye tracking data and provides guidelines for method selection depending on the analysis tasks. PMID- 26357199 TI - A Visual Analytics Approach to Multiscale Exploration of Environmental Time Series. AB - We present a Visual Analytics approach that addresses the detection of interesting patterns in numerical time series, specifically from environmental sciences. Crucial for the detection of interesting temporal patterns are the time scale and the starting points one is looking at. Our approach makes no assumption about time scale and starting position of temporal patterns and consists of three main steps: an algorithm to compute statistical values for all possible time scales and starting positions of intervals, visual identification of potentially interesting patterns in a matrix visualization, and interactive exploration of detected patterns. We demonstrate the utility of this approach in two scientific scenarios and explain how it allowed scientists to gain new insight into the dynamics of environmental systems. PMID- 26357200 TI - The User Puzzle—Explaining the Interaction with Visual Analytics Systems. AB - Visual analytics emphasizes the interplay between visualization, analytical procedures performed by computers and human perceptual and cognitive activities. Human reasoning is an important element in this context. There are several theories in psychology and HCI explaining open-ended and exploratory reasoning. Five of these theories (sensemaking theories, gestalt theories, distributed cognition, graph comprehension theories and skill-rule-knowledge models) are described in this paper. We discuss their relevance for visual analytics. In order to do this more systematically, we developed a schema of categories relevant for visual analytics research and evaluation. All these theories have strengths but also weaknesses in explaining interaction with visual analytics systems. A possibility to overcome the weaknesses would be to combine two or more of these theories. PMID- 26357201 TI - Enterprise Data Analysis and Visualization: An Interview Study. AB - Organizations rely on data analysts to model customer engagement, streamline operations, improve production, inform business decisions, and combat fraud. Though numerous analysis and visualization tools have been built to improve the scale and efficiency at which analysts can work, there has been little research on how analysis takes place within the social and organizational context of companies. To better understand the enterprise analysts' ecosystem, we conducted semi-structured interviews with 35 data analysts from 25 organizations across a variety of sectors, including healthcare, retail, marketing and finance. Based on our interview data, we characterize the process of industrial data analysis and document how organizational features of an enterprise impact it. We describe recurring pain points, outstanding challenges, and barriers to adoption for visual analytic tools. Finally, we discuss design implications and opportunities for visual analysis research. PMID- 26357204 TI - Real-Time 3D Tracking and Reconstruction on Mobile Phones. AB - We present a novel framework for jointly tracking a camera in 3D and reconstructing the 3D model of an observed object. Due to the region based approach, our formulation can handle untextured objects, partial occlusions, motion blur, dynamic backgrounds and imperfect lighting. Our formulation also allows for a very efficient implementation which achieves real-time performance on a mobile phone, by running the pose estimation and the shape optimisation in parallel. We use a level set based pose estimation but completely avoid the, typically required, explicit computation of a global distance. This leads to tracking rates of more than 100 Hz on a desktop PC and 30 Hz on a mobile phone. Further, we incorporate additional orientation information from the phone's inertial sensor which helps us resolve the tracking ambiguities inherent to region based formulations. The reconstruction step first probabilistically integrates 2D image statistics from selected keyframes into a 3D volume, and then imposes coherency and compactness using a total variational regularisation term. The global optimum of the overall energy function is found using a continuous max flow algorithm and we show that, similar to tracking, the integration of per voxel posteriors instead of likelihoods improves the precision and accuracy of the reconstruction. PMID- 26357205 TI - Real-Time RGB-D Camera Relocalization via Randomized Ferns for Keyframe Encoding. AB - Recovery from tracking failure is essential in any simultaneous localization and tracking system. In this context, we explore an efficient keyframe-based relocalization method based on frame encoding using randomized ferns. The method enables automatic discovery of keyframes through online harvesting in tracking mode, and fast retrieval of pose candidates in the case when tracking is lost. Frame encoding is achieved by applying simple binary feature tests which are stored in the nodes of an ensemble of randomized ferns. The concatenation of small block codes generated by each fern yields a global compact representation of camera frames. Based on those representations we define the frame dissimilarity as the block-wise hamming distance (BlockHD). Dissimilarities between an incoming query frame and a large set of keyframes can be efficiently evaluated by simply traversing the nodes of the ferns and counting image co occurrences in corresponding code tables. In tracking mode, those dissimilarities decide whether a frame/pose pair is considered as a novel keyframe. For tracking recovery, poses of the most similar keyframes are retrieved and used for reinitialization of the tracking algorithm. The integration of our relocalization method into a hand-held KinectFusion system allows seamless continuation of mapping even when tracking is frequently lost. PMID- 26357206 TI - Impact of Soft Tissue Heterogeneity on Augmented Reality for Liver Surgery. AB - This paper presents a method for real-time augmented reality of internal liver structures during minimally invasive hepatic surgery. Vessels and tumors computed from pre-operative CT scans can be overlaid onto the laparoscopic view for surgery guidance. Compared to current methods, our method is able to locate the in-depth positions of the tumors based on partial three-dimensional liver tissue motion using a real-time biomechanical model. This model permits to properly handle the motion of internal structures even in the case of anisotropic or heterogeneous tissues, as it is the case for the liver and many anatomical structures. Experimentations conducted on phantom liver permits to measure the accuracy of the augmentation while real-time augmentation on in vivo human liver during real surgery shows the benefits of such an approach for minimally invasive surgery. PMID- 26357207 TI - Using Augmented Reality to Elicit Pretend Play for Children with Autism. AB - Children with autism spectrum condition (ASC) suffer from deficits or developmental delays in symbolic thinking. In particular, they are often found lacking in pretend play during early childhood. Researchers believe that they encounter difficulty in generating and maintaining mental representation of pretense coupled with the immediate reality. We have developed an interactive system that explores the potential of Augmented Reality (AR) technology to visually conceptualize the representation of pretense within an open-ended play environment. Results from an empirical study involving children with ASC aged 4 to 7 demonstrated a significant improvement of pretend play in terms of frequency, duration and relevance using the AR system in comparison to a non computer-assisted situation. We investigated individual differences, skill transfer, system usability and limitations of the proposed AR system. We discuss design guidelines for future AR systems for children with ASC and other pervasive developmental disorders. PMID- 26357208 TI - Augmented Reality Binoculars. AB - In this paper we present an augmented reality binocular system to allow long range high precision augmentation of live telescopic imagery with aerial and terrain based synthetic objects, vehicles, people and effects. The inserted objects must appear stable in the display and must not jitter and drift as the user pans around and examines the scene with the binoculars. The design of the system is based on using two different cameras with wide field of view and narrow field of view lenses enclosed in a binocular shaped shell. Using the wide field of view gives us context and enables us to recover the 3D location and orientation of the binoculars much more robustly, whereas the narrow field of view is used for the actual augmentation as well as to increase precision in tracking. We present our navigation algorithm that uses the two cameras in combination with an inertial measurement unit and global positioning system in an extended Kalman filter and provides jitter free, robust and real-time pose estimation for precise augmentation. We have demonstrated successful use of our system as part of information sharing example as well as a live simulated training system for observer training, in which fixed and rotary wing aircrafts, ground vehicles, and weapon effects are combined with real world scenes. PMID- 26357209 TI - 1.5D Egocentric Dynamic Network Visualization. AB - Dynamic network visualization has been a challenging research topic due to the visual and computational complexity introduced by the extra time dimension. Existing solutions are usually good for overview and presentation tasks, but not for the interactive analysis of a large dynamic network. We introduce in this paper a new approach which considers only the dynamic network central to a focus node, also known as the egocentric dynamic network. Our major contribution is a novel 1.5D visualization design which greatly reduces the visual complexity of the dynamic network without sacrificing the topological and temporal context central to the focus node. In our design, the egocentric dynamic network is presented in a single static view, supporting rich analysis through user interactions on both time and network. We propose a general framework for the 1.5D visualization approach, including the data processing pipeline, the visualization algorithm design, and customized interaction methods. Finally, we demonstrate the effectiveness of our approach on egocentric dynamic network analysis tasks, through case studies and a controlled user experiment comparing with three baseline dynamic network visualization methods. PMID- 26357210 TI - Effect of Text Outline and Contrast Polarity on AR Text Readability in Industrial Lighting. AB - Text readability with augmented reality head-worn displays is critical and at present time, there are no standard guidelines to follow. The readability depends mainly on background lighting, display technology (i.e., OST: optical see-through or VST: video see-through), and text style (e.g., plain text, outline or billboard). In this work, we addressed the readability limits for industrial activities. We experimented the effects of two background illuminances levels (1,000 lx for very fine basic industrial tasks and 4,000 lx for fine machining), two commercially available head-worn display technologies, variable outline widths and contrast polarity of text. We analyzed the performance of 12 subjects by collecting about 3,400 measurements using a specific test application and followed by qualitative interviews. With high illuminances, VST performed better than OST, regardless of contrast polarity and outline width. We found that negative contrast polarity is preferable with VST, and that just a minimum outline (1 px) around black text is optimal. On the contrary, positive contrast polarity should be used with OST and outline is not effective. Therefore, we evaluated the usage limits of the OST by sampling its contrast sensitivity function. PMID- 26357211 TI - On Linear Spaces of Polyhedral Meshes. AB - Polyhedral meshes (PM)-meshes having planar faces-have enjoyed a rise in popularity in recent years due to their importance in architectural and industrial design. However, they are also notoriously difficult to generate and manipulate. Previous methods start with a smooth surface and then apply elaborate meshing schemes to create polyhedral meshes approximating the surface. In this paper, we describe a reverse approach: given the topology of a mesh, we explore the space of possible planar meshes having that topology. Our approach is based on a complete characterization of the maximal linear spaces of polyhedral meshes contained in the curved manifold of polyhedral meshes with a given topology. We show that these linear spaces can be described as nullspaces of differential operators, much like harmonic functions are nullspaces of the Laplacian operator. An analysis of this operator provides tools for global and local design of a polyhedral mesh, which fully expose the geometric possibilities and limitations of the given topology. PMID- 26357212 TI - Temporal Video Filtering and Exposure Control for Perceptual Motion Blur. AB - We propose the computation of a perceptual motion blur in videos. Our technique takes the predicted eye motion into account when watching the video. Compared to traditional motion blur recorded by a video camera our approach results in a perceptual blur that is closer to reality. This postprocess can also be used to simulate different shutter effects or for other artistic purposes. It handles real and artificial video input, is easy to compute and has a low additional cost for rendered content. We illustrate its advantages in a user study using eye tracking. PMID- 26357213 TI - ThemeDelta: Dynamic Segmentations over Temporal Topic Models. AB - We present ThemeDelta, a visual analytics system for extracting and visualizing temporal trends, clustering, and reorganization in time-indexed textual datasets. ThemeDelta is supported by a dynamic temporal segmentation algorithm that integrates with topic modeling algorithms to identify change points where significant shifts in topics occur. This algorithm detects not only the clustering and associations of keywords in a time period, but also their convergence into topics (groups of keywords) that may later diverge into new groups. The visual representation of ThemeDelta uses sinuous, variable-width lines to show this evolution on a timeline, utilizing color for categories, and line width for keyword strength. We demonstrate how interaction with ThemeDelta helps capture the rise and fall of topics by analyzing archives of historical newspapers, of U.S. presidential campaign speeches, and of social messages collected through iNeighbors, a web-based social website. ThemeDelta is evaluated using a qualitative expert user study involving three researchers from rhetoric and history using the historical newspapers corpus. PMID- 26357214 TI - Predicting Microbial Interactions Using Vector Autoregressive Model with Graph Regularization. AB - Microbial interactions play important roles on the structure and function of complex microbial communities. With the rapid accumulation of high-throughput metagenomic or 16S rRNA sequencing data, it is possible to infer complex microbial interactions. Co-occurrence patterns of microbial species among multiple samples are often utilized to infer interactions. There are few methods to consider the temporally interacting patterns among microbial species. In this paper, we present a Graph-regularized Vector Autoregressive (GVAR) model to infer causal relationships among microbial entities. The new model has advantage comparing to the original vector autoregressive (VAR) model. Specifically, GVAR can incorporate similarity information for microbial interaction inference--i.e., GVAR assumed that if two species are similar in the previous stage, they tend to have similar influence on the other species in the next stage. We apply the model on a time series dataset of human gut microbiome which was treated with repeated antibiotics. The experimental results indicate that the new approach has better performance than several other VAR-based models and demonstrate its capability of extracting relevant microbial interactions. PMID- 26357215 TI - Predicting the Pro-Longevity or Anti-Longevity Effect of Model Organism Genes with New Hierarchical Feature Selection Methods. AB - Ageing is a highly complex biological process that is still poorly understood. With the growing amount of ageing-related data available on the web, in particular concerning the genetics of ageing, it is timely to apply data mining methods to that data, in order to try to discover novel patterns that may assist ageing research. In this work, we introduce new hierarchical feature selection methods for the classification task of data mining and apply them to ageing related data from four model organisms: Caenorhabditis elegans (worm), Saccharomyces cerevisiae (yeast), Drosophila melanogaster (fly), and Mus musculus (mouse). The main novel aspect of the proposed feature selection methods is that they exploit hierarchical relationships in the set of features (Gene Ontology terms) in order to improve the predictive accuracy of the Naive Bayes and 1 Nearest Neighbour (1-NN) classifiers, which are used to classify model organisms' genes into pro-longevity or anti-longevity genes. The results show that our hierarchical feature selection methods, when used together with Naive Bayes and 1 NN classifiers, obtain higher predictive accuracy than the standard (without feature selection) Naive Bayes and 1-NN classifiers, respectively. We also discuss the biological relevance of a number of Gene Ontology terms very frequently selected by our algorithms in our datasets. PMID- 26357216 TI - UDoNC: An Algorithm for Identifying Essential Proteins Based on Protein Domains and Protein-Protein Interaction Networks. AB - Prediction of essential proteins which are crucial to an organism's survival is important for disease analysis and drug design, as well as the understanding of cellular life. The majority of prediction methods infer the possibility of proteins to be essential by using the network topology. However, these methods are limited to the completeness of available protein-protein interaction (PPI) data and depend on the network accuracy. To overcome these limitations, some computational methods have been proposed. However, seldom of them solve this problem by taking consideration of protein domains. In this work, we first analyze the correlation between the essentiality of proteins and their domain features based on data of 13 species. We find that the proteins containing more protein domain types which rarely occur in other proteins tend to be essential. Accordingly, we propose a new prediction method, named UDoNC, by combining the domain features of proteins with their topological properties in PPI network. In UDoNC, the essentiality of proteins is decided by the number and the frequency of their protein domain types, as well as the essentiality of their adjacent edges measured by edge clustering coefficient. The experimental results on S. cerevisiae data show that UDoNC outperforms other existing methods in terms of area under the curve (AUC). Additionally, UDoNC can also perform well in predicting essential proteins on data of E. coli. PMID- 26357217 TI - ENISI SDE: A New Web-Based Tool for Modeling Stochastic Processes. AB - Modeling and simulations approaches have been widely used in computational biology, mathematics, bioinformatics and engineering to represent complex existing knowledge and to effectively generate novel hypotheses. While deterministic modeling strategies are widely used in computational biology, stochastic modeling techniques are not as popular due to a lack of user-friendly tools. This paper presents ENISI SDE, a novel web-based modeling tool with stochastic differential equations. ENISI SDE provides user-friendly web user interfaces to facilitate adoption by immunologists and computational biologists. This work provides three major contributions: (1) discussion of SDE as a generic approach for stochastic modeling in computational biology; (2) development of ENISI SDE, a web-based user-friendly SDE modeling tool that highly resembles regular ODE-based modeling; (3) applying ENISI SDE modeling tool through a use case for studying stochastic sources of cell heterogeneity in the context of CD4+ T cell differentiation. The CD4+ T cell differential ODE model has been published [8] and can be downloaded from biomodels.net. The case study reproduces a biological phenomenon that is not captured by the previously published ODE model and shows the effectiveness of SDE as a stochastic modeling approach in biology in general and immunology in particular and the power of ENISI SDE. PMID- 26357218 TI - An Integrated Approach to Sequence-Independent Local Alignment of Protein Binding Sites. AB - Accurate alignment of protein-protein binding sites can aid in protein docking studies and constructing templates for predicting structure of protein complexes, along with in-depth understanding of evolutionary and functional relationships. However, over the past three decades, structural alignment algorithms have focused predominantly on global alignments with little effort on the alignment of local interfaces. In this paper, we introduce the PBSalign (Protein-protein Binding Site alignment) method, which integrates techniques in graph theory, 3D localized shape analysis, geometric scoring, and utilization of physicochemical and geometrical properties. Computational results demonstrate that PBSalign is capable of identifying similar homologous and analogous binding sites accurately and performing alignments with better geometric match measures than existing protein-protein interface comparison tools. The proportion of better alignment quality generated by PBSalign is 46, 56, and 70 percent more than iAlign as judged by the average match index (MI), similarity index (SI), and structural alignment score (SAS), respectively. PBSalign provides the life science community an efficient and accurate solution to binding-site alignment while striking the balance between topological details and computational complexity. PMID- 26357219 TI - P-Finder: Reconstruction of Signaling Networks from Protein-Protein Interactions and GO Annotations. AB - Because most complex genetic diseases are caused by defects of cell signaling, illuminating a signaling cascade is essential for understanding their mechanisms. We present three novel computational algorithms to reconstruct signaling networks between a starting protein and an ending protein using genome-wide protein protein interaction (PPI) networks and gene ontology (GO) annotation data. A signaling network is represented as a directed acyclic graph in a merged form of multiple linear pathways. An advanced semantic similarity metric is applied for weighting PPIs as the preprocessing of all three methods. The first algorithm repeatedly extends the list of nodes based on path frequency towards an ending protein. The second algorithm repeatedly appends edges based on the occurrence of network motifs which indicate the link patterns more frequently appearing in a PPI network than in a random graph. The last algorithm uses the information propagation technique which iteratively updates edge orientations based on the path strength and merges the selected directed edges. Our experimental results demonstrate that the proposed algorithms achieve higher accuracy than previous methods when they are tested on well-studied pathways of S. cerevisiae. Furthermore, we introduce an interactive web application tool, called P-Finder, to visualize reconstructed signaling networks. PMID- 26357220 TI - A New Semantic Functional Similarity over Gene Ontology. AB - Identifying functionally similar or closely related genes and gene products has significant impacts on biological and clinical studies as well as drug discovery. In this paper, we propose an effective and practically useful method measuring both gene and gene product similarity by integrating the topology of gene ontology, known functional domains and their functional annotations. The proposed method is comprehensively evaluated through statistical analysis of the similarities derived from sequence, structure and phylogenetic profiles, and clustering analysis of disease genes clusters. Our results show that the proposed method clearly outperforms other conventional methods. Furthermore, literature analysis also reveals that the proposed method is both statistically and biologically promising for identifying functionally similar genes or gene products. In particular, we demonstrate that the proposed functional similarity metric is capable of discoverying new disease related genes or gene products. PMID- 26357221 TI - A Comparative Assessment of Predictive Accuracies of Conventional and Machine Learning Scoring Functions for Protein-Ligand Binding Affinity Prediction. AB - Accurately predicting the binding affinities of large diverse sets of protein ligand complexes efficiently is a key challenge in computational biomolecular science, with applications in drug discovery, chemical biology, and structural biology. Since a scoring function (SF) is used to score, rank, and identify potential drug leads, the fidelity with which it predicts the affinity of a ligand candidate for a protein's binding site has a significant bearing on the accuracy of virtual screening. Despite intense efforts in developing conventional SFs, which are either force-field based, knowledge-based, or empirical, their limited predictive accuracy has been a major roadblock toward cost-effective drug discovery. Therefore, in this work, we explore a range of novel SFs employing different machine-learning (ML) approaches in conjunction with a variety of physicochemical and geometrical features characterizing protein-ligand complexes. We assess the scoring accuracies of these new ML SFs as well as those of conventional SFs in the context of the 2007 and 2010 PDBbind benchmark datasets on both diverse and protein-family-specific test sets. We also investigate the influence of the size of the training dataset and the type and number of features used on scoring accuracy. We find that the best performing ML SF has a Pearson correlation coefficient of 0.806 between predicted and measured binding affinities compared to 0.644 achieved by a state-of-the-art conventional SF. We also find that ML SFs benefit more than their conventional counterparts from increases in the number of features and the size of training dataset. In addition, they perform better on novel proteins that they were never trained on before. PMID- 26357222 TI - A Fractal Dimension and Wavelet Transform Based Method for Protein Sequence Similarity Analysis. AB - One of the key tasks related to proteins is the similarity comparison of protein sequences in the area of bioinformatics and molecular biology, which helps the prediction and classification of protein structure and function. It is a significant and open issue to find similar proteins from a large scale of protein database efficiently. This paper presents a new distance based protein similarity analysis using a new encoding method of protein sequence which is based on fractal dimension. The protein sequences are first represented into the 1 dimensional feature vectors by their biochemical quantities. A series of Hybrid method involving discrete Wavelet transform, Fractal dimension calculation (HWF) with sliding window are then applied to form the feature vector. At last, through the similarity calculation, we can obtain the distance matrix, by which, the phylogenic tree can be constructed. We apply this approach by analyzing the ND5 (NADH dehydrogenase subunit 5) protein cluster data set. The experimental results show that the proposed model is more accurate than the existing ones such as Su's model, Zhang's model, Yao's model and MEGA software, and it is consistent with some known biological facts. PMID- 26357223 TI - A Property-Driven Methodology for Formal Analysis of Synthetic Biology Systems. AB - This paper proposes a formal methodology to analyse bio-systems, in particular synthetic biology systems. An integrative analysis perspective combining different model checking approaches based on different property categories is provided. The methodology is applied to the synthetic pulse generator system and several verification experiments are carried out to demonstrate the use of our approach to formally analyse various aspects of synthetic biology systems. PMID- 26357224 TI - A Topology Potential-Based Method for Identifying Essential Proteins from PPI Networks. AB - Essential proteins are indispensable for cellular life. It is of great significance to identify essential proteins that can help us understand the minimal requirements for cellular life and is also very important for drug design. However, identification of essential proteins based on experimental approaches are typically time-consuming and expensive. With the development of high-throughput technology in the post-genomic era, more and more protein-protein interaction data can be obtained, which make it possible to study essential proteins from the network level. There have been a series of computational approaches proposed for predicting essential proteins based on network topologies. Most of these topology based essential protein discovery methods were to use network centralities. In this paper, we investigate the essential proteins' topological characters from a completely new perspective. To our knowledge it is the first time that topology potential is used to identify essential proteins from a protein-protein interaction (PPI) network. The basic idea is that each protein in the network can be viewed as a material particle which creates a potential field around itself and the interaction of all proteins forms a topological field over the network. By defining and computing the value of each protein's topology potential, we can obtain a more precise ranking which reflects the importance of proteins from the PPI network. The experimental results show that topology potential-based methods TP and TP-NC outperform traditional topology measures: degree centrality (DC), betweenness centrality (BC), closeness centrality (CC), subgraph centrality (SC), eigenvector centrality (EC), information centrality (IC), and network centrality (NC) for predicting essential proteins. In addition, these centrality measures are improved on their performance for identifying essential proteins in biological network when controlled by topology potential. PMID- 26357225 TI - An Efficient Exact Algorithm for the Motif Stem Search Problem over Large Alphabets. AB - In recent years, there has been an increasing interest in planted (l, d) motif search (PMS) with applications to discovering significant segments in biological sequences. However, there has been little discussion about PMS over large alphabets. This paper focuses on motif stem search (MSS), which is recently introduced to search motifs on large-alphabet inputs. A motif stem is an l-length string with some wildcards. The goal of the MSS problem is to find a set of stems that represents a superset of all (l , d) motifs present in the input sequences, and the superset is expected to be as small as possible. The three main contributions of this paper are as follows: (1) We build motif stem representation more precisely by using regular expressions. (2) We give a method for generating all possible motif stems without redundant wildcards. (3) We propose an efficient exact algorithm, called StemFinder, for solving the MSS problem. Compared with the previous MSS algorithms, StemFinder runs much faster and reports fewer stems which represent a smaller superset of all (l, d) motifs. StemFinder is freely available at http://sites.google.com/site/feqond/stemfinder. PMID- 26357226 TI - An Improved Integral Inequality to Stability Analysis of Genetic Regulatory Networks With Interval Time-Varying Delays. AB - This paper focuses on stability analysis for a class of genetic regulatory networks with interval time-varying delays. An improved integral inequality concerning on double-integral items is first established. Then, we use the improved integral inequality to deal with the resultant double-integral items in the derivative of the involved Lyapunov-Krasovskii functional. As a result, a delay-range-dependent and delay-rate-dependent asymptotical stability criterion is established for genetic regulatory networks with differential time-varying delays. Furthermore, it is theoretically proven that the stability criterion proposed here is less conservative than the corresponding one in [Neurocomputing, 2012, 93: 19-26]. Based on the obtained result, another stability criterion is given under the case that the information of the derivatives of delays is unknown. Finally, the effectiveness of the approach proposed in this paper is illustrated by a pair of numerical examples which give the comparisons of stability criteria proposed in this paper and some literature. PMID- 26357227 TI - Burial Level Change Defines a High Energetic Relevance for Protein Binding Interfaces. AB - Protein-protein interfaces defined through atomic contact or solvent accessibility change are widely adopted in structural biology studies. But, these definitions cannot precisely capture energetically important regions at protein interfaces. The burial depth of an atom in a protein is related to the atom's energy. This work investigates how closely the change in burial level of an atom/residue upon complexation is related to the binding. Burial level change is different from burial level itself. An atom deeply buried in a monomer with a high burial level may not change its burial level after an interaction and it may have little burial level change. We hypothesize that an interface is a region of residues all undergoing burial level changes after interaction. By this definition, an interface can be decomposed into an onion-like structure according to the burial level change extent. We found that our defined interfaces cover energetically important residues more precisely, and that the binding free energy of an interface is distributed progressively from the outermost layer to the core. These observations are used to predict binding hot spots. Our approach's F measure performance on a benchmark dataset of alanine mutagenesis residues is much superior or similar to those by complicated energy modeling or machine learning approaches. PMID- 26357228 TI - Data Requirement for Phylogenetic Inference from Multiple Loci: A New Distance Method. AB - We consider the problem of estimating the evolutionary history of a set of species (phylogeny or species tree) from several genes. It is known that the evolutionary history of individual genes (gene trees) might be topologically distinct from each other and from the underlying species tree, possibly confounding phylogenetic analysis. A further complication in practice is that one has to estimate gene trees from molecular sequences of finite length. We provide the first full data-requirement analysis of a species tree reconstruction method that takes into account estimation errors at the gene level. Under that criterion, we also devise a novel reconstruction algorithm that provably improves over all previous methods in a regime of interest. PMID- 26357229 TI - Gene Selection Integrated with Biological Knowledge for Plant Stress Response Using Neighborhood System and Rough Set Theory. AB - Mining knowledge from gene expression data is a hot research topic and direction of bioinformatics. Gene selection and sample classification are significant research trends, due to the large amount of genes and small size of samples in gene expression data. Rough set theory has been successfully applied to gene selection, as it can select attributes without redundancy. To improve the interpretability of the selected genes, some researchers introduced biological knowledge. In this paper, we first employ neighborhood system to deal directly with the new information table formed by integrating gene expression data with biological knowledge, which can simultaneously present the information in multiple perspectives and do not weaken the information of individual gene for selection and classification. Then, we give a novel framework for gene selection and propose a significant gene selection method based on this framework by employing reduction algorithm in rough set theory. The proposed method is applied to the analysis of plant stress response. Experimental results on three data sets show that the proposed method is effective, as it can select significant gene subsets without redundancy and achieve high classification accuracy. Biological analysis for the results shows that the interpretability is well. PMID- 26357230 TI - GPUDePiCt: A Parallel Implementation of a Clustering Algorithm for Computing Degenerate Primers on Graphics Processing Units. AB - In order to make multiple copies of a target sequence in the laboratory, the technique of Polymerase Chain Reaction (PCR) requires the design of "primers", which are short fragments of nucleotides complementary to the flanking regions of the target sequence. If the same primer is to amplify multiple closely related target sequences, then it is necessary to make the primers "degenerate", which would allow it to hybridize to target sequences with a limited amount of variability that may have been caused by mutations. However, the PCR technique can only allow a limited amount of degeneracy, and therefore the design of degenerate primers requires the identification of reasonably well-conserved regions in the input sequences. We take an existing algorithm for designing degenerate primers that is based on clustering and parallelize it in a web accessible software package GPUDePiCt, using a shared memory model and the computing power of Graphics Processing Units (GPUs). We test our implementation on large sets of aligned sequences from the human genome and show a multi-fold speedup for clustering using our hybrid GPU/CPU implementation over a pure CPU approach for these sequences, which consist of more than 7,500 nucleotides. We also demonstrate that this speedup is consistent over larger numbers and longer lengths of aligned sequences. PMID- 26357231 TI - Identification of Protein Complexes from Tandem Affinity Purification/Mass Spectrometry Data via Biased Random Walk. AB - Systematic identification of protein complexes from protein-protein interaction networks (PPIs) is an important application of data mining in life science. Over the past decades, various new clustering techniques have been developed based on modelling PPIs as binary relations. Non-binary information of co-complex relations (prey/bait) in PPIs data derived from tandem affinity purification/mass spectrometry (TAP-MS) experiments has been unfairly disregarded. In this paper, we propose a Biased Random Walk based algorithm for detecting protein complexes from TAP-MS data, resulting in the random walk with restarting baits (RWRB). RWRB is developed based on Random walk with restart. The main contribution of RWRB is the incorporation of co-complex relations in TAP-MS PPI networks into the clustering process, by implementing a new restarting strategy during the process of random walk. Through experimentation on un-weighted and weighted TAP-MS data sets, we validated biological significance of our results by mapping them to manually curated complexes. Results showed that, by incorporating non-binary, co membership information, significant improvement has been achieved in terms of both statistical measurements and biological relevance. Better accuracy demonstrates that the proposed method outperformed several state-of-the-art clustering algorithms for the detection of protein complexes in TAP-MS data. PMID- 26357232 TI - Identifying Driver Nodes in the Human Signaling Network Using Structural Controllability Analysis. AB - Cell signaling governs the basic cellular activities and coordinates the actions in cell. Abnormal regulations in cell signaling processing are responsible for many human diseases, such as diabetes and cancers. With the accumulation of massive data related to human cell signaling, it is feasible to obtain a human signaling network. Some studies have shown that interesting biological phenomenon and drug-targets could be discovered by applying structural controllability analysis to biological networks. In this work, we apply structural controllability to a human signaling network and detect driver nodes, providing a systematic analysis of the role of different proteins in controlling the human signaling network. We find that the proteins in the upstream of the signaling information flow and the low in-degree proteins play a crucial role in controlling the human signaling network. Interestingly, inputting different control signals on the regulators of the cancer-associated genes could cost less than controlling the cancer-associated genes directly in order to control the whole human signaling network in the sense that less drive nodes are needed. This research provides a fresh perspective for controlling the human cell signaling system. PMID- 26357233 TI - Improving Integration Effectiveness of ID Mapping Based Biological Record Linkage. AB - Traditionally, biological objects such as genes, proteins, and pathways are represented by a convenient identifier, or ID, which is then used to cross reference, link and describe objects in biological databases. Relationships among the objects are often established using non-trivial and computationally complex ID mapping systems or converters, and are stored in authoritative databases such as UniGene, GeneCards, PIR and BioMart. Despite best efforts, such mappings are largely incomplete and riddled with false negatives. Consequently, data integration using record linkage that relies on these mappings produces poor quality of data, inadvertently leading to erroneous conclusions. In this paper, we discuss this largely ignored dimension of data integration, examine how the ubiquitous use of identifiers in biological databases is a significant barrier to knowledge fusion using distributed computational pipelines, and propose two algorithms for ad hoc and restriction free ID mapping of arbitrary types using online resources. We also propose two declarative statements for ID conversion and data integration based on ID mapping on-the-fly. PMID- 26357235 TI - More Efficient Virtual Shadow Maps for Many Lights. AB - Recently, several algorithms have been introduced that enable real-time performance for many lights in applications such as games. In this paper, we explore the use of hardware-supported virtual cube-map shadows to efficiently implement high-quality shadows from hundreds of light sources in real time and within a bounded memory footprint. In addition, we explore the utility of ray tracing for shadows from many lights and present a hybrid algorithm combining ray tracing with cube maps to exploit their respective strengths. Our solution supports real-time performance with hundreds of lights in fully dynamic high detail scenes. PMID- 26357234 TI - Multiple Break-Points Detection in Array CGH Data via the Cross-Entropy Method. AB - Array comparative genome hybridization (aCGH) is a widely used methodology to detect copy number variations of a genome in high resolution. Knowing the number of break-points and their corresponding locations in genomic sequences serves different biological needs. Primarily, it helps to identify disease-causing genes that have functional importance in characterizing genome wide diseases. For human autosomes the normal copy number is two, whereas at the sites of oncogenes it increases (gain of DNA) and at the tumour suppressor genes it decreases (loss of DNA). The majority of the current detection methods are deterministic in their set-up and use dynamic programming or different smoothing techniques to obtain the estimates of copy number variations. These approaches limit the search space of the problem due to different assumptions considered in the methods and do not represent the true nature of the uncertainty associated with the unknown break points in genomic sequences. We propose the Cross-Entropy method, which is a model-based stochastic optimization technique as an exact search method, to estimate both the number and locations of the break-points in aCGH data. We model the continuous scale log-ratio data obtained by the aCGH technique as a multiple break-point problem. The proposed methodology is compared with well established publicly available methods using both artificially generated data and real data. Results show that the proposed procedure is an effective way of estimating number and especially the locations of break-points with high level of precision. Availability: The methods described in this article are implemented in the new R package breakpoint and it is available from the Comprehensive R Archive Network at http://CRAN.R-project.org/package=breakpoint. PMID- 26357236 TI - A Distributed Memory Hierarchy and Data Management for Interactive Scene Navigation and Modification on Tiled Display Walls. AB - Simultaneous modification and navigation of massive 3D models are difficult because repeated data edits affect the data layout and coherency on a secondary storage, which in turn affect the interactive out-of-core rendering performance. In this paper, we propose a novel approach for distributed data management for simultaneous interactive navigation and modification of massive 3D data using the readily available infrastructure of a tiled display. Tiled multi-displays, projection or LCD panel based, driven by a PC cluster, can be viewed as a cluster of storage-compute-display (SCD) nodes. Given a cluster of SCD node infrastructure, we first propose a distributed memory hierarchy for interactive rendering applications. Second, in order to further reduce the latency in such applications, we propose a new data partitioning approach for distributed storage among the SCD nodes that reduces the variance in the data load across the SCD nodes. Our data distribution method takes in a data set of any size, and reorganizes it into smaller partitions, and stores it across the multiple SCD nodes. These nodes store, manage, and coordinate data with other SCD nodes to simultaneously achieve interactive navigation and modification. Specifically, the data is not duplicated across these distributed secondary storage devices. In addition, coherency in data access, due to screen-space adjacency of adjacent displays in the tile, as well as object space adjacency of the data sets, is well leveraged in the design of the data management technique. Empirical evaluation on two large data sets, with different data density distribution, demonstrates that the proposed data management approach achieves superior performance over alternative state-of-the-art methods. PMID- 26357237 TI - An Efficient Framework for Generating Storyline Visualizations from Streaming Data. AB - This paper presents a novel framework for applying storyline visualizations to streaming data. The framework includes three components: a new data management scheme for processing and storing the incoming data, a layout construction algorithm specifically designed for incrementally generating storylines from streaming data, and a layout refinement algorithm for improving the legibility of the visualization. By dividing the layout computation to two separate components, one for constructing and another for refining, our framework effectively provides the users with the ability to follow and reason dynamic data. The evaluation studies of our storyline visualization framework demonstrate its efficacy to present streaming data as well as its superior performance over existing methods in terms of both computational efficiency and visual clarity. PMID- 26357238 TI - Fast Edge-Aware Processing via First Order Proximal Approximation. AB - We present a new framework for fast edge-aware processing of images and videos. The proposed smoothing method is based on an optimization formulation with a non convex sparse regularization for a better smoothing behavior near strong edges. We develop mathematical tools based on first order approximation of proximal operators to accelerate the proposed method while maintaining high-quality smoothing. The first order approximation is used to estimate a solution of the proximal form in a half-quadratic solver, and also to derive a warm-start solution that can be calculated quickly when the image is loaded by the user. We extend the method to large-scale processing by estimating the smoothing operation with independent 1D convolution operations. This approach linearly scales to the size of the image and can fully take advantage of parallel processing. The method supports full color filtering and turns out to be temporally coherent for fast video processing. We demonstrate the performance of the proposed method on various applications including image smoothing, detail manipulation, HDR tone mapping, fast edge simplification and video edge-aware processing. PMID- 26357239 TI - Query2Question: Translating Visualization Interaction into Natural Language. AB - Richly interactive visualization tools are increasingly popular for data exploration and analysis in a wide variety of domains. Existing systems and techniques for recording provenance of interaction focus either on comprehensive automated recording of low-level interaction events or on idiosyncratic manual transcription of high-level analysis activities. In this paper, we present the architecture and translation design of a query-to-question (Q2Q) system that automatically records user interactions and presents them semantically using natural language (written English). Q2Q takes advantage of domain knowledge and uses natural language generation (NLG) techniques to translate and transcribe a progression of interactive visualization states into a visual log of styled text that complements and effectively extends the functionality of visualization tools. We present Q2Q as a means to support a cross-examination process in which questions rather than interactions are the focus of analytic reasoning and action. We describe the architecture and implementation of the Q2Q system, discuss key design factors and variations that effect question generation, and present several visualizations that incorporate Q2Q for analysis in a variety of knowledge domains. PMID- 26357240 TI - Virtual Training: Learning Transfer of Assembly Tasks. AB - In training assembly workers in a factory, there are often barriers such as cost and lost productivity due to shutdown. The use of virtual reality (VR) training has the potential to reduce these costs. This research compares virtual bimanual haptic training versus traditional physical training and the effectiveness for learning transfer. In a mixed experimental design, participants were assigned to either virtual or physical training and trained by assembling a wooden burr puzzle as many times as possible during a twenty minute time period. After training, participants were tested using the physical puzzle and were retested again after two weeks. All participants were trained using brightly colored puzzle pieces. To examine the effect of color, testing involved the assembly of colored physical parts and natural wood colored physical pieces. Spatial ability as measured using a mental rotation test, was shown to correlate with the number of assemblies they were able to complete in the training. While physical training outperformed virtual training, after two weeks the virtually trained participants actually improved their test assembly times. The results suggest that the color of the puzzle pieces helped the virtually trained participants in remembering the assembly process. PMID- 26357241 TI - A Modular Framework for Digital Painting. AB - While there has been tremendous research in the simulation of natural media painting, little academic work has been written to understand how all these contributions interrelate and to use this knowledge to direct future work. In this paper, we survey the set of interesting artistic tools to categorize their effects and motivate a modular framework for digital painting that can reproduce those effects in a loosely coupled way. We use this framework as a lens through which we survey the literature and classify the achievements of previous efforts. We examine our own contributions in the field in more detail, discussing how the framework motivated those results and how it impacted our accomplishments. Finally, we discuss the open challenges that remain for the research community, and how the framework can help to make contributions towards those challenges. PMID- 26357242 TI - Effects of Field of View and Visual Complexity on Virtual Reality Training Effectiveness for a Visual Scanning Task. AB - Virtual reality training systems are commonly used in a variety of domains, and it is important to understand how the realism of a training simulation influences training effectiveness. We conducted a controlled experiment to test the effects of display and scenario properties on training effectiveness for a visual scanning task in a simulated urban environment. The experiment varied the levels of field of view and visual complexity during a training phase and then evaluated scanning performance with the simulator's highest levels of fidelity and scene complexity. To assess scanning performance, we measured target detection and adherence to a prescribed strategy. The results show that both field of view and visual complexity significantly affected target detection during training; higher field of view led to better performance and higher visual complexity worsened performance. Additionally, adherence to the prescribed visual scanning strategy during assessment was best when the level of visual complexity during training matched that of the assessment conditions, providing evidence that similar visual complexity was important for learning the technique. The results also demonstrate that task performance during training was not always a sufficient measure of mastery of an instructed technique. That is, if learning a prescribed strategy or skill is the goal of a training exercise, performance in a simulation may not be an appropriate indicator of effectiveness outside of training-evaluation in a more realistic setting may be necessary. PMID- 26357244 TI - Fast Wavefront Propagation (FWP) for Computing Exact Geodesic Distances on Meshes. AB - Computing geodesic distances on triangle meshes is a fundamental problem in computational geometry and computer graphics. To date, two notable classes of algorithms, the Mitchell-Mount-Papadimitriou (MMP) algorithm and the Chen-Han (CH) algorithm, have been proposed. Although these algorithms can compute exact geodesic distances if numerical computation is exact, they are computationally expensive, which diminishes their usefulness for large-scale models and/or time critical applications. In this paper, we propose the fast wavefront propagation (FWP) framework for improving the performance of both the MMP and CH algorithms. Unlike the original algorithms that propagate only a single window (a data structure locally encodes geodesic information) at each iteration, our method organizes windows with a bucket data structure so that it can process a large number of windows simultaneously without compromising wavefront quality. Thanks to its macro nature, the FWP method is less sensitive to mesh triangulation than the MMP and CH algorithms. We evaluate our FWP-based MMP and CH algorithms on a wide range of large-scale real-world models. Computational results show that our method can improve the speed by a factor of 3-10. PMID- 26357243 TI - Exploration of the Brain's White Matter Structure through Visual Abstraction and Multi-Scale Local Fiber Tract Contraction. AB - We present a visualization technique for brain fiber tracts from DTI data that provides insight into the structure of white matter through visual abstraction. We achieve this abstraction by analyzing the local similarity of tract segment directions at different scales using a stepwise increase of the search range. Next, locally similar tract segments are moved toward each other in an iterative process, resulting in a local contraction of tracts perpendicular to the local tract direction at a given scale. This not only leads to the abstraction of the global structure of the white matter as represented by the tracts, but also creates volumetric voids. This increase of empty space decreases the mutual occlusion of tracts and, consequently, results in a better understanding of the brain's three-dimensional fiber tract structure. Our implementation supports an interactive and continuous transition between the original and the abstracted representations via various scale levels of similarity. We also support the selection of groups of tracts, which are highlighted and rendered with the abstracted visualization as context. PMID- 26357245 TI - High-Quality Depth Estimation Using an Exemplar 3D Model for Stereo Conversion. AB - High-quality depth painting for each object in a scene is a challenging task in 2D to 3D stereo conversion. One way to accurately estimate the varying depth within the object in an image is to utilize existing 3D models. Automatic pose estimation approaches based on 2D-3D feature correspondences have been proposed to obtain depth from a given 3D model. However, when the 3D model is not identical to the target object, previous methods often produce erroneous depth in the vicinity of the silhouette of the object. This paper introduces a novel 3D model-based depth estimation method that effectively produces high-quality depth information for rigid objects in a stereo conversion workflow. Given an exemplar 3D model and user correspondences, our method generates detailed depth of an object by optimizing the initial depth obtained by the application of structural fitting and silhouette matching in the image domain. The final depth is accurate up to the given 3D model, while consistent with the image. Our method was applied to various image sequences containing objects with different appearances and varying poses. The experiments show that our method can generate plausible depth information that can be utilized for high-quality 2D to 3D stereo conversion. PMID- 26357246 TI - Human Motion Capture Data Tailored Transform Coding. AB - Human motion capture (mocap) is a widely used technique for digitalizing human movements. With growing usage, compressing mocap data has received increasing attention, since compact data size enables efficient storage and transmission. Our analysis shows that mocap data have some unique characteristics that distinguish themselves from images and videos. Therefore, directly borrowing image or video compression techniques, such as discrete cosine transform, does not work well. In this paper, we propose a novel mocap-tailored transform coding algorithm that takes advantage of these features. Our algorithm segments the input mocap sequences into clips, which are represented in 2D matrices. Then it computes a set of data-dependent orthogonal bases to transform the matrices to frequency domain, in which the transform coefficients have significantly less dependency. Finally, the compression is obtained by entropy coding of the quantized coefficients and the bases. Our method has low computational cost and can be easily extended to compress mocap databases. It also requires neither training nor complicated parameter setting. Experimental results demonstrate that the proposed scheme significantly outperforms state-of-the-art algorithms in terms of compression performance and speed. PMID- 26357247 TI - SI-Cut: Structural Inconsistency Analysis for Image Foreground Extraction. AB - This paper presents a novel approach for extracting foreground objects from an image. Existing methods involve separating the foreground and background mainly according to their color distributions and neighbor similarities. This paper proposes using a more discriminative strategy, structural inconsistency analysis, in which the localities of color and texture are considered. Given an indicated rectangle, the proposed system iteratively maximizes the consensus regions between the original image and predicted structures from the known background. The object contour can then be extracted according to inconsistency in the predicted background and foreground structures. The proposed method includes an efficient image completion technique for structural prediction. The results of experiments showed that the extraction accuracy of the proposed method is higher than that of related methods for structural scenes, and is also comparable to that of related methods for less structural situations. PMID- 26357248 TI - Variational Mesh Denoising Using Total Variation and Piecewise Constant Function Space. AB - Mesh surface denoising is a fundamental problem in geometry processing. The main challenge is to remove noise while preserving sharp features (such as edges and corners) and preventing generating false edges. We propose in this paper to combine total variation (TV) and piecewise constant function space for variational mesh denoising. We first give definitions of piecewise constant function spaces and associated operators. A variational mesh denoising method will then be presented by combining TV and piecewise constant function space. It is proved that, the solution of the variational problem (the key part of the method) is in some sense continuously dependent on its parameter, indicating that the solution is robust to small perturbations of this parameter. To solve the variational problem, we propose an efficient iterative algorithm (with an additional algorithmic parameter) based on variable splitting and augmented Lagrangian method, each step of which has closed form solution. Our denoising method is discussed and compared to several typical existing methods in various aspects. Experimental results show that our method outperforms all the compared methods for both CAD and non-CAD meshes at reasonable costs. It can preserve different levels of features well, and prevent generating false edges in most cases, even with the parameters evaluated by our estimation formulae. PMID- 26357249 TI - Optimization Integrator for Large Time Steps. AB - Practical time steps in today's state-of-the-art simulators typically rely on Newton's method to solve large systems of nonlinear equations. In practice, this works well for small time steps but is unreliable at large time steps at or near the frame rate, particularly for difficult or stiff simulations. We show that recasting backward Euler as a minimization problem allows Newton's method to be stabilized by standard optimization techniques with some novel improvements of our own. The resulting solver is capable of solving even the toughest simulations at the [Formula: see text] frame rate and beyond. We show how simple collisions can be incorporated directly into the solver through constrained minimization without sacrificing efficiency. We also present novel penalty collision formulations for self collisions and collisions against scripted bodies designed for the unique demands of this solver. Finally, we show that these techniques improve the behavior of Material Point Method (MPM) simulations by recasting it as an optimization problem. PMID- 26357250 TI - View-Dependent Adaptive Cloth Simulation with Buckling Compensation. AB - This paper describes a method for view-dependent cloth simulation using dynamically adaptive mesh refinement and coarsening. Given a prescribed camera motion, the method adjusts the criteria controlling refinement to account for visibility and apparent size in the camera's view. Objectionable dynamic artifacts are avoided by anticipative refinement and smoothed coarsening, while locking in extremely coarsened regions is inhibited by modifying the material model to compensate for unresolved sub-element buckling. This approach preserves the appearance of detailed cloth throughout the animation while avoiding the wasted effort of simulating details that would not be discernible to the viewer. The computational savings realized by this method increase as scene complexity grows. The approach produces a 2* speed-up for a single character and more than 4* for a small group as compared to view-independent adaptive simulations, and respectively 5* and 9* speed-ups as compared to non-adaptive simulations. PMID- 26357251 TI - Scalable Parallel Distance Field Construction for Large-Scale Applications. AB - Computing distance fields is fundamental to many scientific and engineering applications. Distance fields can be used to direct analysis and reduce data. In this paper, we present a highly scalable method for computing 3D distance fields on massively parallel distributed-memory machines. A new distributed spatial data structure, named parallel distance tree, is introduced to manage the level sets of data and facilitate surface tracking over time, resulting in significantly reduced computation and communication costs for calculating the distance to the surface of interest from any spatial locations. Our method supports several data types and distance metrics from real-world applications. We demonstrate its efficiency and scalability on state-of-the-art supercomputers using both large scale volume datasets and surface models. We also demonstrate in-situ distance field computation on dynamic turbulent flame surfaces for a petascale combustion simulation. Our work greatly extends the usability of distance fields for demanding applications. PMID- 26357252 TI - k(+)-buffer: An Efficient, Memory-Friendly and Dynamic k-buffer Framework. AB - Depth-sorted fragment determination is fundamental for a host of image-based techniques which simulates complex rendering effects. It is also a challenging task in terms of time and space required when rasterizing scenes with high depth complexity. When low graphics memory requirements are of utmost importance, k buffer can objectively be considered as the most preferred framework which advantageously ensures the correct depth order on a subset of all generated fragments. Although various alternatives have been introduced to partially or completely alleviate the noticeable quality artifacts produced by the initial k buffer algorithm in the expense of memory increase or performance downgrade, appropriate tools to automatically and dynamically compute the most suitable value of k are still missing. To this end, we introduce k(+)-buffer, a fast framework that accurately simulates the behavior of k-buffer in a single rendering pass. Two memory-bounded data structures: (i) the max-array and (ii) the max-heap are developed on the GPU to concurrently maintain the k-foremost fragments per pixel by exploring pixel synchronization and fragment culling. Memory-friendly strategies are further introduced to dynamically (a) lessen the wasteful memory allocation of individual pixels with low depth complexity frequencies, (b) minimize the allocated size of k-buffer according to different application goals and hardware limitations via a straightforward depth histogram analysis and (c) manage local GPU cache with a fixed-memory depth-sorting mechanism. Finally, an extensive experimental evaluation is provided demonstrating the advantages of our work over all prior k-buffer variants in terms of memory usage, performance cost and image quality. PMID- 26357253 TI - Exploring Curved Schematization of Territorial Outlines. AB - Hand-drawn schematized maps traditionally make extensive use of curves. However, there are few automated approaches for curved schematization; most previous work focuses on straight lines. We present a new algorithm for area-preserving curved schematization of territorial outlines. Our algorithm converts a simple polygon into a schematic crossing-free representation using circular arcs. We use two basic operations to iteratively replace consecutive arcs until the desired complexity is reached. Our results are not restricted to arcs ending at input vertices. The method can be steered towards different degrees of "curviness": we can encourage or discourage the use of arcs with a large central angle via a single parameter. Our method creates visually pleasing results even for very low output complexities. To evaluate the effectiveness of our design choices, we present a geometric evaluation of the resulting schematizations. Besides the geometric qualities of our algorithm, we also investigate the potential of curved schematization as a concept. We conducted an online user study investigating the effectiveness of curved schematizations compared to straight-line schematizations. While the visual complexity of curved shapes was judged higher than that of straight-line shapes, users generally preferred curved schematizations. We observed that curves significantly improved the ability of users to match schematized shapes of moderate complexity to their unschematized equivalents. PMID- 26357254 TI - Semantic Enrichment of Movement Behavior with Foursquare--A Visual Analytics Approach. AB - In recent years, many approaches have been developed that efficiently and effectively visualize movement data, e.g., by providing suitable aggregation strategies to reduce visual clutter. Analysts can use them to identify distinct movement patterns, such as trajectories with similar direction, form, length, and speed. However, less effort has been spent on finding the semantics behind movements, i.e. why somebody or something is moving. This can be of great value for different applications, such as product usage and consumer analysis, to better understand urban dynamics, and to improve situational awareness. Unfortunately, semantic information often gets lost when data is recorded. Thus, we suggest to enrich trajectory data with POI information using social media services and show how semantic insights can be gained. Furthermore, we show how to handle semantic uncertainties in time and space, which result from noisy, unprecise, and missing data, by introducing a POI decision model in combination with highly interactive visualizations. Finally, we evaluate our approach with two case studies on a large electric scooter data set and test our model on data with known ground truth. PMID- 26357255 TI - Moment Invariants for 2D Flow Fields via Normalization in Detail. AB - The analysis of 2D flow data is often guided by the search for characteristic structures with semantic meaning. One way to approach this question is to identify structures of interest by a human observer, with the goal of finding similar structures in the same or other datasets. The major challenges related to this task are to specify the notion of similarity and define respective pattern descriptors. While the descriptors should be invariant to certain transformations, such as rotation and scaling, they should provide a similarity measure with respect to other transformations, such as deformations. In this paper, we propose to use moment invariants as pattern descriptors for flow fields. Moment invariants are one of the most popular techniques for the description of objects in the field of image recognition. They have recently also been applied to identify 2D vector patterns limited to the directional properties of flow fields. Moreover, we discuss which transformations should be considered for the application to flow analysis. In contrast to previous work, we follow the intuitive approach of moment normalization, which results in a complete and independent set of translation, rotation, and scaling invariant flow field descriptors. They also allow to distinguish flow features with different velocity profiles. We apply the moment invariants in a pattern recognition algorithm to a real world dataset and show that the theoretical results can be extended to discrete functions in a robust way. PMID- 26357256 TI - Robustness-Based Simplification of 2D Steady and Unsteady Vector Fields. AB - Vector field simplification aims to reduce the complexity of the flow by removing features in order of their relevance and importance, to reveal prominent behavior and obtain a compact representation for interpretation. Most existing simplification techniques based on the topological skeleton successively remove pairs of critical points connected by separatrices, using distance or area-based relevance measures. These methods rely on the stable extraction of the topological skeleton, which can be difficult due to instability in numerical integration, especially when processing highly rotational flows. In this paper, we propose a novel simplification scheme derived from the recently introduced topological notion of robustness which enables the pruning of sets of critical points according to a quantitative measure of their stability, that is, the minimum amount of vector field perturbation required to remove them. This leads to a hierarchical simplification scheme that encodes flow magnitude in its perturbation metric. Our novel simplification algorithm is based on degree theory and has minimal boundary restrictions. Finally, we provide an implementation under the piecewise-linear setting and apply it to both synthetic and real-world datasets. We show local and complete hierarchical simplifications for steady as well as unsteady vector fields. PMID- 26357257 TI - All-Frequency Direct Illumination with Vectorized Visibility. AB - Many existing pre-computed radiance transfer (PRT) approaches for all-frequency lighting store the information of a 3D object in the pre-vertex manner. To preserve the fidelity of high frequency effects, the 3D object must be tessellated densely. Otherwise, rendering artifacts due to interpolation may appear. This paper presents an all-frequency lighting algorithm for direct illumination based on a new visibility representation which approximates a visibility function using a sequence of 3D vectors. The algorithm is able to construct the visibility function of an on-screen pixel on-the-fly. Hence even though the 3D object is not tessellated densely, the rendering artifacts can be suppressed greatly. Besides, a summed area table based rendering algorithm, which is able to handle the integration over a non-axis aligned polygon, is developed. Using our approach, we can rotate lighting environment, change view point, and adjust the shininess of the 3D object in a real-time manner. Experimental results show that our approach can render plausible all-frequency lighting effects for direct illumination in real-time, especially for specular shadows, which are difficult for other methods to obtain. PMID- 26357258 TI - Disambiguating Stereoscopic Transparency Using a Thaumatrope Approach. AB - Volume rendering is a popular visualization technique for scientific computing and medical imaging. By assigning proper transparency, it allows us to see more information inside the volume. However, because volume rendering projects complex 3D structures into the 2D domain, the resultant visualization often suffers from ambiguity and its spatial relationship could be difficult to recognize correctly, especially when the scene or setting is highly transparent. Stereoscopic displays are not the rescue to the problem even though they add an additional dimension which seems helpful for resolving the ambiguity. This paper proposes a thaumatrope method to enhance 3D understanding with stereoscopic transparency for volume rendering. Our method first generates an additional cue with less spatial ambiguity by using a high opacity setting. To avoid cluttering the actual content, we only select its prominent feature for displaying. By alternating the actual content and the selected feature quickly, the viewer only perceives a whole volume while its spatial understanding has been enhanced. A user study was performed to compare the proposed method with the original stereoscopic volume rendering and the static combination of the actual content and the selected feature using a 3D display. Results show that the proposed thaumatrope approach provides better spatial understanding than compared approaches. PMID- 26357259 TI - Evaluating Texture Compression Masking Effects Using Objective Image Quality Assessment Metrics. AB - Texture compression is widely used in real-time rendering to reduce storage and bandwidth requirements. Recent research in compression algorithms has explored both reduced fixed bit rate and variable bit rate algorithms. The results are evaluated at the individual texture level using mean square error, peak signal-to noise ratio, or visual image inspection. We argue this is the wrong evaluation approach. Compression artifacts in individual textures are likely visually masked in final rendered images and this masking is not accounted for when evaluating individual textures. This masking comes from both geometric mapping of textures onto models and the effects of combining different textures on the same model such as diffuse, gloss, and bump maps. We evaluate final rendered images using rigorous perceptual error metrics. Our method samples the space of viewpoints in a scene, renders the scene from each viewpoint using variations of compressed textures, and then compares each to a ground truth using uncompressed textures from the same viewpoint. We show that masking has a significant effect on final rendered image quality, masking effects and perceptual sensitivity to masking varies by the type of texture, graphics hardware compression algorithms are too conservative, and reduced bit rates are possible while maintaining final rendered image quality. PMID- 26357260 TI - Glyph-Based Video Visualization for Semen Analysis. AB - The existing efforts in computer assisted semen analysis have been focused on high speed imaging and automated image analysis of sperm motility. This results in a large amount of data, and it is extremely challenging for both clinical scientists and researchers to interpret, compare and correlate the multidimensional and time-varying measurements captured from video data. In this work, we use glyphs to encode a collection of numerical measurements taken at a regular interval and to summarize spatio-temporal motion characteristics using static visual representations. The design of the glyphs addresses the needs for (a) encoding some 20 variables using separable visual channels, (b) supporting scientific observation of the interrelationships between different measurements and comparison between different sperm cells and their flagella, and (c) facilitating the learning of the encoding scheme by making use of appropriate visual abstractions and metaphors. As a case study, we focus this work on video visualization for computer-aided semen analysis, which has a broad impact on both biological sciences and medical healthcare. We demonstrate that glyph-based visualization can serve as a means of external memorization of video data as well as an overview of a large set of spatiotemporal measurements. It enables domain scientists to make scientific observation in a cost-effective manner by reducing the burden of viewing videos repeatedly, while providing them with a new visual representation for conveying semen statistics. PMID- 26357261 TI - Sorting Linear Genomes with Rearrangements and Indels. AB - Rearrangements are mutations that can change the organization of a genome, but not its content. Examples are inversions of DNA segments, translocations of chromosome ends, fusions and fissions of chromosomes. All mentioned rearrangements can be represented by the generic Double Cut and Join (DCJ) operation. However, the DCJ operation also allows circular chromosomes to be created at intermediate steps, even if the compared genomes are linear. In this case it is more plausible to consider a restriction in which the reincorporation of a circular chromosome has to be done immediately after its creation. We call these two consecutive operations an ER composition. It has been shown that an ER composition mimics either an internal block interchange (when two segments in the same chromosome exchange their positions), or an internal transposition (the special case of a block interchange when the two segments are adjacent). The DCJ distance of two genomes is the same, regardless of this restriction, and can be computed in linear time. For comparing two genomes with unequal contents, in addition to rearrangements we have to allow insertions and deletions of DNA segments-named indels. It is already known that the distance in the model combining DCJ and indel operations can be exactly computed. Again, for linear genomes it would be more plausible to adopt a restricted version with ER compositions. This model was studied recently by da Silva et al. (BMC Bioinformatics 13, Suppl. 19, S14, 2012), but only an upper bound for the restricted DCJ-indel distance was provided. Here we first solve an open problem posed in that paper and present a very simple proof showing that the distance, which can be computed in linear time, is the same for both the unrestricted and the restricted DCJ-indel models. We then give a simpler algorithm for computing an optimal restricted DCJ-indel sorting scenario in O(n log n) time. We also relate the DCJ-indel distance to the restricted DCJ-substitution distance, which instead of indels considers a more powerful operation that allows the substitution of a DNA segment by another DNA segment. We show that the DCJ-indel distance is a 2-approximation for the restricted DCJ-substitution distance. PMID- 26357262 TI - Product Grammars for Alignment and Folding. AB - We develop a theory of algebraic operations over linear and context-free grammars that makes it possible to combine simple "atomic" grammars operating on single sequences into complex, multi-dimensional grammars. We demonstrate the utility of this framework by constructing the search spaces of complex alignment problems on multiple input sequences explicitly as algebraic expressions of very simple one dimensional grammars. In particular, we provide a fully worked frameshift-aware, semiglobal DNA-protein alignment algorithm whose grammar is composed of products of small, atomic grammars. The compiler accompanying our theory makes it easy to experiment with the combination of multiple grammars and different operations. Composite grammars can be written out in L(A)T(E)X for documentation and as a guide to implementation of dynamic programming algorithms. An embedding in Haskell as a domain-specific language makes the theory directly accessible to writing and using grammar products without the detour of an external compiler. Software and supplemental files available here: http://www.bioinf. uni leipzig.de/Software/gramprod/. PMID- 26357263 TI - Multiple 3D RNA Structure Superposition Using Neighbor Joining. AB - Recent advances in RNA research and the steady growth of available RNA structures call for bioinformatics methods for handling and analyzing RNA structural data. Recently, we introduced SETTER-a fast and accurate method for RNA pairwise structure alignment. In this paper, we describe MultiSETTER, SETTER extension for multiple RNA structure alignment. MultiSETTER combines SETTER's decomposition of RNA structures into non-overlapping structural subunits with the multiple sequence alignment algorithm ClustalW adapted for the structure alignment. The accuracy of MultiSETTER was assessed by the automatic classification of RNA structures and its comparison to SCOR annotations. In addition, MultiSETTER classification was also compared to multiple sequence alignment-based and secondary structure alignment-based classifications provided by LocARNA and RNADistance tools, respectively. MultiSETTER precompiled Windows libraries, as well as the C++ source code, are freely available from http://siret.cz/multisetter. PMID- 26357264 TI - Improving Retrieval Efficacy of Homology Searches Using the False Discovery Rate. AB - Over the past few decades, discovery based on sequence homology has become a widely accepted practice. Consequently, comparative accuracy of retrieval algorithms (e.g., BLAST) has been rigorously studied for improvement. Unlike most components of retrieval algorithms, the E-value threshold criterion has yet to be thoroughly investigated. An investigation of the threshold is important as it exclusively dictates which sequences are declared relevant and irrelevant. In this paper, we introduce the false discovery rate (FDR) statistic as a replacement for the uniform threshold criterion in order to improve efficacy in retrieval systems. Using NCBI's BLAST and PSI-BLAST software packages, we demonstrate the applicability of such a replacement in both non-iterative (BLASTFDR) and iterative (PSI-BLAST(FDR)) homology searches. For each application, we performed an evaluation of retrieval efficacy with five different multiple testing methods on a large training database. For each algorithm, we choose the best performing method, Benjamini-Hochberg, as the default statistic. As measured by the threshold average precision, BLAST(FDR) yielded 14.1 percent better retrieval performance than BLAST on a large (5,161 queries) test database and PSI-BLAST(FDR) attained 11.8 percent better retrieval performance than PSI BLAST. The C++ source code specific to BLAST(FDR) and PSI-BLAST(FDR) and instructions are available at http://www.cs.mtsu.edu/~hcarroll/blast_fdr/. PMID- 26357265 TI - A Bayesian Framework for Combining Protein and Network Topology Information for Predicting Protein-Protein Interactions. AB - Computational methods for predicting protein-protein interactions are important tools that can complement high-throughput technologies and guide biologists in designing new laboratory experiments. The proteins and the interactions between them can be described by a network which is characterized by several topological properties. Information about proteins and interactions between them, in combination with knowledge about topological properties of the network, can be used for developing computational methods that can accurately predict unknown protein-protein interactions. This paper presents a supervised learning framework based on Bayesian inference for combining two types of information: i) network topology information, and ii) information related to proteins and the interactions between them. The motivation of our model is that by combining these two types of information one can achieve a better accuracy in predicting protein protein interactions, than by using models constructed from these two types of information independently. PMID- 26357266 TI - A Machine Learning Approach for Accurate Annotation of Noncoding RNAs. AB - Searching genomes to locate noncoding RNA genes with known secondary structure is an important problem in bioinformatics. In general, the secondary structure of a searched noncoding RNA is defined with a structure model constructed from the structural alignment of a set of sequences from its family. Computing the optimal alignment between a sequence and a structure model is the core part of an algorithm that can search genomes for noncoding RNAs. In practice, a single structure model may not be sufficient to capture all crucial features important for a noncoding RNA family. In this paper, we develop a novel machine learning approach that can efficiently search genomes for noncoding RNAs with high accuracy. During the search procedure, a sequence segment in the searched genome sequence is processed and a feature vector is extracted to represent it. Based on the feature vector, a classifier is used to determine whether the sequence segment is the searched ncRNA or not. Our testing results show that this approach is able to efficiently capture crucial features of a noncoding RNA family. Compared with existing search tools, it significantly improves the accuracy of genome annotation. PMID- 26357267 TI - A Partial Least Squares Based Procedure for Upstream Sequence Classification in Prokaryotes. AB - The upstream region of coding genes is important for several reasons, for instance locating transcription factor, binding sites, and start site initiation in genomic DNA. Motivated by a recently conducted study, where multivariate approach was successfully applied to coding sequence modeling, we have introduced a partial least squares (PLS) based procedure for the classification of true upstream prokaryotic sequence from background upstream sequence. The upstream sequences of conserved coding genes over genomes were considered in analysis, where conserved coding genes were found by using pan-genomics concept for each considered prokaryotic species. PLS uses position specific scoring matrix (PSSM) to study the characteristics of upstream region. Results obtained by PLS based method were compared with Gini importance of random forest (RF) and support vector machine (SVM), which is much used method for sequence classification. The upstream sequence classification performance was evaluated by using cross validation, and suggested approach identifies prokaryotic upstream region significantly better to RF (p-value < 0.01) and SVM (p-value < 0.01). Further, the proposed method also produced results that concurred with known biological characteristics of the upstream region. PMID- 26357268 TI - An Accurate de novo Algorithm for Glycan Topology Determination from Mass Spectra. AB - Determining the glycan topology automatically from mass spectra represents a great challenge. Existing methods fall into approximate and exact ones. The former including greedy and heuristic ones can reduce the computational complexity, but suffer from information lost in the procedure of glycan interpretation. The latter including dynamic programming and exhaustive enumeration are much slower than the former. In the past years, nearly all emerging methods adopted a tree structure to represent a glycan. They share such problems as repetitive peak counting in reconstructing a candidate structure. Besides, tree-based glycan representation methods often have to give different computational formulas for binary and ternary glycans. We propose a new directed acyclic graph structure for glycan representation. Based on it, this work develops a de novo algorithm to accurately reconstruct the tree structure iteratively from mass spectra with logical constraints and some known biosynthesis rules, by a single computational formula. The experiments on multiple complex glycans extracted from human serum show that the proposed algorithm can achieve higher accuracy to determine a glycan topology than prior methods without increasing computational burden. PMID- 26357269 TI - Colored Noise Induced Bistable Switch in the Genetic Toggle Switch Systems. AB - Noise can induce various dynamical behaviors in nonlinear systems. White noise perturbed systems have been extensively investigated during the last decades. In gene networks, experimentally observed extrinsic noise is colored. As an attempt, we investigate the genetic toggle switch systems perturbed by colored extrinsic noise and with kinetic parameters. Compared with white noise perturbed systems, we show there also exists optimal colored noise strength to induce the best stochastic switch behaviors in the single toggle switch, and the best synchronized switching in the networked systems, which demonstrate that noise induced optimal switch behaviors are widely in existence. Moreover, under a wide range of system parameter regions, we find there exist wider ranges of white and colored noises strengths to induce good switch and synchronization behaviors, respectively; therefore, white noise is beneficial for switch and colored noise is beneficial for population synchronization. Our observations are very robust to extrinsic stimulus strength, cell density, and diffusion rate. Finally, based on the Waddington's epigenetic landscape and the Wiener-Khintchine theorem, physical mechanisms underlying the observations are interpreted. Our investigations can provide guidelines for experimental design, and have potential clinical implications in gene therapy and synthetic biology. PMID- 26357270 TI - COSPEDTree: COuplet Supertree by Equivalence Partitioning of Taxa Set and DAG Formation. AB - From a set of phylogenetic trees with overlapping taxa set, a supertree exhibits evolutionary relationships among all input taxa. The key is to resolve the contradictory relationships with respect to input trees, between individual taxa subsets. Formulation of this NP hard problem employs either local search heuristics to reduce tree search space, or resolves the conflicts with respect to fixed or varying size subtree level decompositions. Different approximation techniques produce supertrees with considerable performance variations. Moreover, the majority of the algorithms involve high computational complexity, thus not suitable for use on large biological data sets. Current study presents COSPEDTree, a novel method for supertree construction. The technique resolves source tree conflicts by analyzing couplet (taxa pair) relationships for each source trees. Subsequently, individual taxa pairs are resolved with a single relation. To prioritize the consensus relations among individual taxa pairs for resolving them, greedy scoring is employed to assign higher score values for the consensus relations among a taxa pair. Selected set of relations resolving individual taxa pairs is subsequently used to construct a directed acyclic graph (DAG). Vertices of DAG represents a taxa subset inferred from the same speciation event. Thus, COSPEDTree can generate non-binary supertrees as well. Depth first traversal on this DAG yields final supertree. According to the performance metrics on branch dissimilarities (such as FP, FN and RF), COSPEDTree produces mostly conservative, well resolved supertrees. Specifically, RF metrics are mostly lower compared to the reference approaches, and FP values are lower apart from only strictly conservative (or veto) approaches. COSPEDTree has worst case time and space complexities of cubic and quadratic order, respectively, better or comparable to the reference approaches. Such high performance and low computational costs enable COSPEDTree to be applied on large scale biological data sets. PMID- 26357271 TI - DAPD: A Knowledgebase for Diabetes Associated Proteins. AB - Recent advancements in genomics and proteomics provide a solid foundation for understanding the pathogenesis of diabetes. Proteomics of diabetes associated pathways help to identify the most potent target for the management of diabetes. The relevant datasets are scattered in various prominent sources which takes much time to select the therapeutic target for the clinical management of diabetes. However, additional information about target proteins is needed for validation. This lacuna may be resolved by linking diabetes associated genes, pathways and proteins and it will provide a strong base for the treatment and planning management strategies of diabetes. Thus, a web source "Diabetes Associated Proteins Database (DAPD)" has been developed to link the diabetes associated genes, pathways and proteins using PHP, MySQL. The current version of DAPD has been built with proteins associated with different types of diabetes. In addition, DAPD has been linked to external sources to gain the access to more participatory proteins and their pathway network. DAPD will reduce the time and it is expected to pave the way for the discovery of novel anti-diabetic leads using computational drug designing for diabetes management. DAPD is open accessed via following url www.mkarthikeyan.bioinfoau.org/dapd. PMID- 26357272 TI - Disulfide Connectivity Prediction Based on Modelled Protein 3D Structural Information and Random Forest Regression. AB - Disulfide connectivity is an important protein structural characteristic. Accurately predicting disulfide connectivity solely from protein sequence helps to improve the intrinsic understanding of protein structure and function, especially in the post-genome era where large volume of sequenced proteins without being functional annotated is quickly accumulated. In this study, a new feature extracted from the predicted protein 3D structural information is proposed and integrated with traditional features to form discriminative features. Based on the extracted features, a random forest regression model is performed to predict protein disulfide connectivity. We compare the proposed method with popular existing predictors by performing both cross-validation and independent validation tests on benchmark datasets. The experimental results demonstrate the superiority of the proposed method over existing predictors. We believe the superiority of the proposed method benefits from both the good discriminative capability of the newly developed features and the powerful modelling capability of the random forest. The web server implementation, called TargetDisulfide, and the benchmark datasets are freely available at: http://csbio.njust.edu.cn/bioinf/TargetDisulfide for academic use. PMID- 26357273 TI - Evolutionary Model Selection and Parameter Estimation for Protein-Protein Interaction Network Based on Differential Evolution Algorithm. AB - Revealing the underlying evolutionary mechanism plays an important role in understanding protein interaction networks in the cell. While many evolutionary models have been proposed, the problem about applying these models to real network data, especially for differentiating which model can better describe evolutionary process for the observed network remains a challenge. The traditional way is to use a model with presumed parameters to generate a network, and then evaluate the fitness by summary statistics, which however cannot capture the complete network structures information and estimate parameter distribution. In this work, we developed a novel method based on Approximate Bayesian Computation and modified Differential Evolution algorithm (ABC-DEP) that is capable of conducting model selection and parameter estimation simultaneously and detecting the underlying evolutionary mechanisms for PPI networks more accurately. We tested our method for its power in differentiating models and estimating parameters on simulated data and found significant improvement in performance benchmark, as compared with a previous method. We further applied our method to real data of protein interaction networks in human and yeast. Our results show duplication attachment model as the predominant evolutionary mechanism for human PPI networks and Scale-Free model as the predominant mechanism for yeast PPI networks. PMID- 26357274 TI - Extraction of Individual Filaments from 2D Confocal Microscopy Images of Flat Cells. AB - A crucial step in understanding the architecture of cells and tissues from microscopy images, and consequently explain important biological events such as wound healing and cancer metastases, is the complete extraction and enumeration of individual filaments from the cellular cytoskeletal network. Current efforts at quantitative estimation of filament length distribution, architecture and orientation from microscopy images are predominantly limited to visual estimation and indirect experimental inference. Here we demonstrate the application of a new algorithm to reliably estimate centerlines of biological filament bundles and extract individual filaments from the centerlines by systematically disambiguating filament intersections. We utilize a filament enhancement step followed by reverse diffusion based filament localization and an integer programming based set combination to systematically extract accurate filaments automatically from microscopy images. Experiments on simulated and real confocal microscope images of flat cells (2D images) show efficacy of the new method. PMID- 26357275 TI - Finding All Longest Common Segments in Protein Structures Efficiently. AB - The Local/Global Alignment (Zemla, 2003), or LGA, is a popular method for the comparison of protein structures. One of the two components of LGA requires us to compute the longest common contiguous segments between two protein structures. That is, given two structures A = (a1, ... ,a(n)) and B = (b1, ... ,b(n)) where a(k), b(k) ? R(3), we are to find, among all the segments f = (a(i), ... ,a(j)) and g = (b(i), ... ,b(j)) that fulfill a certain criterion regarding their similarity, those of the maximum length. We consider the following criteria: (1) the root mean squared deviation (RMSD) between f and g is to be within a given t ? R; (2) f and g can be superposed such that for each k, i <= k <= j, ||a(k) - b(k)|| <= t for a given t ? R. We give an algorithm of O(n log n + nl) time complexity when the first requirement applies, where l is the maximum length of the segments fulfilling the criterion. We show an FPTAS which, for any epsilon ? R, finds a segment of length at least l, but of RMSD up to (1 + epsilon)t, in O(n log n + n/epsilon) time. We propose an FPTAS which for any given epsilon ? R, finds all the segments f and g of the maximum length which can be superposed such that for each k, i <= k <= j, ||a(k) - b(k)|| <= (1 + epsilon)t, thus fulfilling the second requirement approximately. The algorithm has a time complexity of O(n log(2) n/epsilon(5)) when consecutive points in A are separated by the same distance (which is the case with protein structures). These worst-case runtime complexities are verified using C++ implementations of the algorithms, which we have made available at http://alcs.sourceforge.net/. PMID- 26357276 TI - Finding Patterns in Protein Sequences by Using a Hybrid Multiobjective Teaching Learning Based Optimization Algorithm. AB - Proteins are molecules that form the mass of living beings. These proteins exist in dissociated forms like amino-acids and carry out various biological functions, in fact, almost all body reactions occur with the participation of proteins. This is one of the reasons why the analysis of proteins has become a major issue in biology. In a more concrete way, the identification of conserved patterns in a set of related protein sequences can provide relevant biological information about these protein functions. In this paper, we present a novel algorithm based on teaching learning based optimization (TLBO) combined with a local search function specialized to predict common patterns in sets of protein sequences. This population-based evolutionary algorithm defines a group of individuals (solutions) that enhance their knowledge (quality) by means of different learning stages. Thus, if we correctly adapt it to the biological context of the mentioned problem, we can get an acceptable set of quality solutions. To evaluate the performance of the proposed technique, we have used six instances composed of different related protein sequences obtained from the PROSITE database. As we will see, the designed approach makes good predictions and improves the quality of the solutions found by other well-known biological tools. PMID- 26357277 TI - Functional Impact of Autophagy-Related Genes on the Homeostasis and Dynamics of Pancreatic Cancer Cell Lines. AB - Pancreatic cancer is a highly aggressive and chemotherapy-resistant malignant neoplasm. In basal condition, it is characterized by elevated autophagy activity, which is required for tumor growth and that correlates with treatment failure. We analyzed the expression of autophagy related genes in different pancreatic cancer cell lines. A correlation-based network analysis evidenced the sociality and topological roles of the autophagy-related genes after serum starvation. Structural and functional tests identified a core set of autophagy related genes, suggesting different scenarios of autophagic responses to starvation, which may be responsible for the clinical variations associated with pancreatic cancer pathogenesis. PMID- 26357278 TI - Identification of Genomic Aberrations in Cancer Subclones from Heterogeneous Tumor Samples. AB - Tumor samples are usually heterogeneous, containing admixture of more than one kind of tumor subclones. Studies of genomic aberrations from heterogeneous tumor data are hindered by the mixed signal of tumor subclone cells. Most of the existing algorithms cannot distinguish contributions of different subclones from the measured single nucleotide polymorphism (SNP) array signals, which may cause erroneous estimation of genomic aberrations. Here, we have introduced a computational method, Cancer Heterogeneity Analysis from SNP-array Experiments (CHASE), to automatically detect subclone proportions and genomic aberrations from heterogeneous tumor samples. Our method is based on HMM, and incorporates EM algorithm to build a statistical model for modeling mixed signal of multiple tumor subclones. We tested the proposed approach on simulated datasets and two real datasets, and the results show that the proposed method can efficiently estimate tumor subclone proportions and recovery the genomic aberrations. PMID- 26357279 TI - Parameterized BLOSUM Matrices for Protein Alignment. AB - Protein alignment is a basic step for many molecular biology researches. The BLOSUM matrices, especially BLOSUM62, are the de facto standard matrices for protein alignments. However, after widely utilization of the matrices for 15 years, programming errors were surprisingly found in the initial version of source codes for their generation. And amazingly, after bug correction, the "intended" BLOSUM62 matrix performs consistently worse than the "miscalculated" one. In this paper, we find linear relationships among the eigenvalues of the matrices and propose an algorithm to find optimal unified eigenvectors. With them, we can parameterize matrix BLOSUMx for any given variable x that could change continuously. We compare the effectiveness of our parameterized isentropic matrix with BLOSUM62. Furthermore, an iterative alignment and matrix selection process is proposed to adaptively find the best parameter and globally align two sequences. Experiments are conducted on aligning 13,667 families of Pfam database and on clustering MHC II protein sequences, whose improved accuracy demonstrates the effectiveness of our proposed method. PMID- 26357280 TI - Searching High-Order SNP Combinations for Complex Diseases Based on Energy Distribution Difference. AB - Single nucleotide polymorphisms, a dominant type of genetic variants, have been used successfully to identify defective genes causing human single gene diseases. However, most common human diseases are complex diseases and caused by gene-gene and gene-environment interactions. Many SNP-SNP interaction analysis methods have been introduced but they are not powerful enough to discover interactions more than three SNPs. The paper proposes a novel method that analyzes all SNPs simultaneously. Different from existing methods, the method regards an individual's genotype data on a list of SNPs as a point with a unit of energy in a multi-dimensional space, and tries to find a new coordinate system where the energy distribution difference between cases and controls reaches the maximum. The method will find different multiple SNPs combinatorial patterns between cases and controls based on the new coordinate system. The experiment on simulated data shows that the method is efficient. The tests on the real data of age-related macular degeneration (AMD) disease show that it can find out more significant multi-SNP combinatorial patterns than existing methods. PMID- 26357281 TI - Supervised Variational Relevance Learning, An Analytic Geometric Feature Selection with Applications to Omic Datasets. AB - We introduce Supervised Variational Relevance Learning (Suvrel), a variational method to determine metric tensors to define distance based similarity in pattern classification, inspired in relevance learning. The variational method is applied to a cost function that penalizes large intraclass distances and favors small interclass distances. We find analytically the metric tensor that minimizes the cost function. Preprocessing the patterns by doing linear transformations using the metric tensor yields a dataset which can be more efficiently classified. We test our methods using publicly available datasets, for some standard classifiers. Among these datasets, two were tested by the MAQC-II project and, even without the use of further preprocessing, our results improve on their performance. PMID- 26357282 TI - Systematic Biological Filter Design with a Desired I/O Filtering Response Based on Promoter-RBS Libraries. AB - In this study, robust biological filters with an external control to match a desired input/output (I/O) filtering response are engineered based on the well characterized promoter-RBS libraries and a cascade gene circuit topology. In the field of synthetic biology, the biological filter system serves as a powerful detector or sensor to sense different molecular signals and produces a specific output response only if the concentration of the input molecular signal is higher or lower than a specified threshold. The proposed systematic design method of robust biological filters is summarized into three steps. Firstly, several well characterized promoter-RBS libraries are established for biological filter design by identifying and collecting the quantitative and qualitative characteristics of their promoter-RBS components via nonlinear parameter estimation method. Then, the topology of synthetic biological filter is decomposed into three cascade gene regulatory modules, and an appropriate promoter-RBS library is selected for each module to achieve the desired I/O specification of a biological filter. Finally, based on the proposed systematic method, a robust externally tunable biological filter is engineered by searching the promoter-RBS component libraries and a control inducer concentration library to achieve the optimal reference match for the specified I/O filtering response. PMID- 26357283 TI - Bridging Theory with Practice: An Exploratory Study of Visualization Use and Design for Climate Model Comparison. AB - Evaluation methodologies in visualization have mostly focused on how well the tools and techniques cater to the analytical needs of the user. While this is important in determining the effectiveness of the tools and advancing the state of-the-art in visualization research, a key area that has mostly been overlooked is how well established visualization theories and principles are instantiated in practice. This is especially relevant when domain experts, and not visualization researchers, design visualizations for analysis of their data or for broader dissemination of scientific knowledge. There is very little research on exploring the synergistic capabilities of cross-domain collaboration between domain experts and visualization researchers. To fill this gap, in this paper we describe the results of an exploratory study of climate data visualizations conducted in tight collaboration with a pool of climate scientists. The study analyzes a large set of static climate data visualizations for identifying their shortcomings in terms of visualization design. The outcome of the study is a classification scheme that categorizes the design problems in the form of a descriptive taxonomy. The taxonomy is a first attempt for systematically categorizing the types, causes, and consequences of design problems in visualizations created by domain experts. We demonstrate the use of the taxonomy for a number of purposes, such as, improving the existing climate data visualizations, reflecting on the impact of the problems for enabling domain experts in designing better visualizations, and also learning about the gaps and opportunities for future visualization research. We demonstrate the applicability of our taxonomy through a number of examples and discuss the lessons learnt and implications of our findings. PMID- 26357284 TI - Guided Adaptive Image Smoothing via Directional Anisotropic Structure Measurement. AB - Image smoothing prefers a good metric to identify dominant structures from textures adaptive of intensity contrast. In this paper, we drop on a novel directional anisotropic structure measurement (DASM) toward adaptive image smoothing. With observations on psychological perception regarding anisotropy, non-periodicity and local directionality, DASM can well characterize structures and textures independent on their contrast scales. By using such measurement as constraint, we design a guided adaptive image smoothing scheme by improving extrema localization and envelopes construction in a structure-aware manner. Our approach can well suppresses the staircase-like artifacts and blur of structures that appear in previous methods, which better suits structure-preserving image smoothing task. The algorithm is performed on a space-filling curve as the reduced domain, so it is very fast and much easy to implement in practice. We make comprehensive comparisons with previous state-of-the-art methods for a variety of applications. Experimental results demonstrate the merit using our DASM as metric to identify structures, and the effectiveness and efficiency of our adaptive image smoothing approach to produce commendable results. PMID- 26357285 TI - Learning Visualizations by Analogy: Promoting Visual Literacy through Visualization Morphing. AB - We propose the concept of teaching (and learning) unfamiliar visualizations by analogy, that is, demonstrating an unfamiliar visualization method by linking it to another more familiar one, where the in-betweens are designed to bridge the gap of these two visualizations and explain the difference in a gradual manner. As opposed to a textual description, our morphing explains an unfamiliar visualization through purely visual means. We demonstrate our idea by ways of four visualization pair examples: data table and parallel coordinates, scatterplot matrix and hyperbox, linear chart and spiral chart, and hierarchical pie chart and treemap. The analogy is commutative i.e. any member of the pair can be the unfamiliar visualization. A series of studies showed that this new paradigm can be an effective teaching tool. The participants could understand the unfamiliar visualization methods in all of the four pairs either fully or at least significantly better after they observed or interacted with the transitions from the familiar counterpart. The four examples suggest how helpful visualization pairings be identified and they will hopefully inspire other visualization morphings and associated transition strategies to be identified. PMID- 26357286 TI - Parallel Structured Mesh Generation with Disparity Maps by GPU Implementation. AB - The goal of structured mesh is to generate a compressed representation of the 3D surface, where near objects are provided with more details than objects far from the camera, according to the disparity map. The solution is based on the Kohonens Self-Organizing Map algorithm for the benefits of its ability to generate a topological map according to a probability distribution and its potential to be a natural massive parallel algorithm. The disparity map, which stands for a density distribution that reflects the proximity of objects to the camera, is partitioned into an appropriate number of cell units, in such a way that each cell is associated to a processing unit and responsible of a certain area of the plane. The advantage of the proposed model is that it is decentralized and based on data decomposition. The required processing units and memory are with linearly increasing relationship to the problem size. Experimental results show that our GPU implementation is able to provide near real-time performance with small size disparity maps and the running time increases in a linear way with a very weak increasing coefficient. The proposed method is suitable to deal with large scale problems in a massively parallel way. PMID- 26357287 TI - Regularization Based Iterative Point Match Weighting for Accurate Rigid Transformation Estimation. AB - Feature extraction and matching (FEM) for 3D shapes finds numerous applications in computer graphics and vision for object modeling, retrieval, morphing, and recognition. However, unavoidable incorrect matches lead to inaccurate estimation of the transformation relating different datasets. Inspired by AdaBoost, this paper proposes a novel iterative re-weighting method to tackle the challenging problem of evaluating point matches established by typical FEM methods. Weights are used to indicate the degree of belief that each point match is correct. Our method has three key steps: (i) estimation of the underlying transformation using weighted least squares, (ii) penalty parameter estimation via minimization of the weighted variance of the matching errors, and (iii) weight re-estimation taking into account both matching errors and information learnt in previous iterations. A comparative study, based on real shapes captured by two laser scanners, shows that the proposed method outperforms four other state-of-the-art methods in terms of evaluating point matches between overlapping shapes established by two typical FEM methods, resulting in more accurate estimates of the underlying transformation. This improved transformation can be used to better initialize the iterative closest point algorithm and its variants, making 3D shape registration more likely to succeed. PMID- 26357288 TI - Uncertainty-Aware Multidimensional Ensemble Data Visualization and Exploration. AB - This paper presents an efficient visualization and exploration approach for modeling and characterizing the relationships and uncertainties in the context of a multidimensional ensemble dataset. Its core is a novel dissimilarity-preserving projection technique that characterizes not only the relationships among the mean values of the ensemble data objects but also the relationships among the distributions of ensemble members. This uncertainty-aware projection scheme leads to an improved understanding of the intrinsic structure in an ensemble dataset. The analysis of the ensemble dataset is further augmented by a suite of visual encoding and exploration tools. Experimental results on both artificial and real world datasets demonstrate the effectiveness of our approach. PMID- 26357289 TI - VisDock: A Toolkit for Cross-Cutting Interactions in Visualization. AB - Standard user applications provide a range of cross-cutting interaction techniques that are common to virtually all such tools: selection, filtering, navigation, layer management, and cut-and-paste. We present VisDock, a JavaScript mixin library that provides a core set of these cross-cutting interaction techniques for visualization, including selection (lasso, paths, shape selection, etc), layer management (visibility, transparency, set operations, etc), navigation (pan, zoom, overview, magnifying lenses, etc), and annotation (point based, region-based, data-space based, etc). To showcase the utility of the library, we have released it as Open Source and integrated it with a large number of existing web-based visualizations. Furthermore, we have evaluated VisDock using qualitative studies with both developers utilizing the toolkit to build new web-based visualizations, as well as with end-users utilizing it to explore movie ratings data. Results from these studies highlight the usability and effectiveness of the toolkit from both developer and end-user perspectives. PMID- 26357290 TI - Assessing the Ability of a VR-Based Assembly Task Simulation to Evaluate Physical Risk Factors. AB - Nowadays the process of workstation design tends to include assessment steps in a virtual environment (VE) to evaluate the ergonomic features. These approaches are cost-effective and convenient since working directly on the digital mock-up in a VE is preferable to constructing a real physical mock-up in a real environment (RE). This study aimed at understanding the ability of a VR-based assembly tasks simulator to evaluate physical risk factors in ergonomics. Sixteen subjects performed simplified assembly tasks in RE and VE. Motion of the upper body and five muscle electromyographic activities were recorded to compute normalized and averaged objective indicators of discomfort, that is, rapid upper limb assessment score, averaged muscle activations, and total task time. Rated perceived exertion (RPE) and a questionnaire were used as subjective indicators of discomfort. The timing regime and complexity of the assembly tasks were investigated as within subject factors. The results revealed significant differences between measured indicators in RE and VE. While objective measures indicated lower activity and exposure in VE, the subjects experienced more discomfort than in RE. Fairly good correlation levels were found between RE and VE for six of the objective indicators. This study clearly demonstrates that ergonomic studies of assembly tasks using VR are still challenging. Indeed, objective and subjective measurements of discomfort that are usually used in ergonomics to minimize the risks of work-related musculoskeletal disorders development exhibit opposite trends in RE and VE. Nevertheless, the high level of correlation found during this study indicates that the VR-based simulator can be used for such assessments. PMID- 26357291 TI - Bas-Relief Modeling from Normal Images with Intuitive Styles. AB - Traditional 3D model-based bas-relief modeling methods are often limited to model dependent and monotonic relief styles. This paper presents a novel method for digital bas-relief modeling with intuitive style control. Given a composite normal image, the problem discussed in this paper involves generating a discontinuity-free depth field with high compression of depth data while preserving or even enhancing fine details. In our framework, several layers of normal images are composed into a single normal image. The original normal image on each layer is usually generated from 3D models or through other techniques as described in this paper. The bas-relief style is controlled by choosing a parameter and setting a targeted height for them. Bas-relief modeling and stylization are achieved simultaneously by solving a sparse linear system. Different from previous work, our method can be used to freely design bas-reliefs in normal image space instead of in object space, which makes it possible to use any popular image editing tools for bas-relief modeling. Experiments with a wide range of 3D models and scenes show that our method can effectively generate digital bas-reliefs. PMID- 26357292 TI - Blood Flow Clustering and Applications in Virtual Stenting of Intracranial Aneurysms. AB - Understanding the hemodynamics of blood flow in vascular pathologies such as intracranial aneurysms is essential for both their diagnosis and treatment. Computational fluid dynamics (CFD) simulations of blood flow based on patient individual data are performed to better understand aneurysm initiation and progression and more recently, for predicting treatment success. In virtual stenting, a flow-diverting mesh tube (stent) is modeled inside the reconstructed vasculature and integrated in the simulation. We focus on steady-state simulation and the resulting complex multiparameter data. The blood flow pattern captured therein is assumed to be related to the success of stenting. It is often visualized by a dense and cluttered set of streamlines.We present a fully automatic approach for reducing visual clutter and exposing characteristic flow structures by clustering streamlines and computing cluster representatives. While individual clustering techniques have been applied before to streamlines in 3D flow fields, we contribute a general quantitative and a domain-specific qualitative evaluation of three state-of-the-art techniques. We show that clustering based on streamline geometry as well as on domain-specific streamline attributes contributes to comparing and evaluating different virtual stenting strategies. With our work, we aim at supporting CFD engineers and interventional neuroradiologists. PMID- 26357293 TI - Chess Evolution Visualization. AB - We present a chess visualization to convey the changes in a game over successive generations. It contains a score chart, an evolution graph and a chess board, such that users can understand a game from global to local viewpoints. Unlike current graphical chess tools, which focus only on highlighting pieces that are under attack and require sequential investigation, our visualization shows potential outcomes after a piece is moved and indicates how much tactical advantage the player can have over the opponent. Users can first glance at the score chart to roughly obtain the growth and decline of advantages from both sides, and then examine the position relations and the piece placements, to know how the pieces are controlled and how the strategy works. To achieve this visualization, we compute the decision tree using artificial intelligence to analyze a game, in which each node represents a chess position and each edge connects two positions that are one-move different. We then merge nodes representing the same chess position, and shorten branches where nodes on them contain only two neighbors, in order to achieve readability. During the graph rendering, the nodes containing events such as draws, effective checks and checkmates, are highlighted because they show how a game is ended. As a result, our visualization helps players understand a chess game so that they can efficiently learn strategies and tactics. The presented results, evaluations, and the conducted user studies demonstrate the feasibility of our visualization design. PMID- 26357294 TI - Exact and Adaptive Signed Distance Fields Computation for Rigid and Deformable Models on GPUs. AB - Most techniques for real-time construction of a signed distance field, whether on a CPU or GPU, involve approximate distances. We use a GPU to build an exact adaptive distance field, constructed from an octree by using the Morton code. We use rectangle-swept spheres to construct a bounding volume hierarchy (BVH) around a triangulated model. To speed up BVH construction, we can use a multi-BVH structure to improve the workload balance between GPU processors. An upper bound on distance to the model provided by the octree itself allows us to reduce the number of BVHs involved in determining the distances from the centers of octree nodes at successively lower levels, prior to an exact distance query involving the remaining BVHs. Distance fields can be constructed 35-64 times as fast as a serial CPU implementation of a similar algorithm, allowing us to simulate a piece of fabric interacting with the Stanford Bunny at 20 frames per second. PMID- 26357295 TI - GazeVis: Interactive 3D Gaze Visualization for Contiguous Cross-Sectional Medical Images. AB - Gaze visualization has been used to understand the results from gaze tracking studies in a wide range of fields. In the medical field, diagnoses of medical images have been studied with gaze tracking technology to understand how radiologists read medical images. While prior work were mainly based on diagnosis with a single image, recent work focused on diagnosis with consecutive cross sectional medical images acquired from preoperative computed tomography (CT) or magnetic resonance imaging (MRI). In the diagnosis, radiologists scroll through a stack of images to get a 3D cognition of organs and lesions. Thus, it is important to understand radiologists' gaze patterns three dimensionally across such contiguous cross-sectional images. However, little has been done to visualize more complicated gaze patterns from the contiguous cross-sectional medical images. To address this problem, we present an interactive 3D gaze visualization tool, GazeVis, where InfoVis and SciVis techniques are harmonized to show the abstract gaze data along with a realistic 3D rendering of the visual stimuli (i.e., organs and lesions). We present case studies with 12 radiologists who use GazeVis to investigate gaze patterns of their colleagues with different levels of expertise, providing empirical evidences about the competence of our gaze visualization system. PMID- 26357296 TI - GraphDiaries: Animated Transitions andTemporal Navigation for Dynamic Networks. AB - Identifying, tracking and understanding changes in dynamic networks are complex and cognitively demanding tasks. We present GraphDiaries, a visual interface designed to improve support for these tasks in any node-link based graph visualization system. GraphDiaries relies on animated transitions that highlight changes in the network between time steps, thus helping users identify and understand those changes. To better understand the tasks related to the exploration of dynamic networks, we first introduce a task taxonomy, that informs the design of GraphDiaries, presented afterwards. We then report on a user study, based on representative tasks identified through the taxonomy, and that compares GraphDiaries to existing techniques for temporal navigation in dynamic networks, showing that it outperforms them in terms of both task time and errors for several of these tasks. PMID- 26357297 TI - Hierarchical and Controlled Advancement for Continuous Collision Detection of Rigid and Articulated Models. AB - We present fast CCD algorithm for general rigid and articulated models based on conservative advancement. We have implemented the CCD algorithm with two different acceleration techniques which can handle rigid models, and have extended one of them to articulated models. The resulting algorithms take a few milliseconds for rigid models with tens of thousands of triangles, and a few milliseconds for articulated models with tens of links. We show that the performance of our algorithms is much faster than existing CCD algorithms for polygon-soup models and it is also comparable to competing CCD algorithms that are limited to manifold models. PMID- 26357298 TI - Importance-Driven Accessory Lights Design for Enhancing Local Shapes. AB - We introduce a semi-automatic lighting design method that deploys per-voxel accessory lights (fill and detail lights) to enhance local shapes, as well as to increase the perceptibility and visual saliency of an object. Our approach allows the user to manually design arbitrary lights in a scene for creating the desired feeling of emotion. The user designed lights are used as key lights and our approach automatically configures per-voxel accessory lights that preserve the user designed feeling of emotion. Per-voxel fill lights brighten the shadows and thus increase the perceptibility and visual saliency. Per-voxel detail lights enhance the visual cues for the local shape perception. Moreover, the revealed local shapes are controlled by the user employing an importance distribution. Similarly, the perceptibility and visual saliency are also controlled based on an importance distribution. Our perceptual measurement guarantees that the revealed local shapes are independent of the key lights. In addition, our method provides two control parameters, which adjust the fill and detail lights, to provide the user with additional flexibility in designing the expected lighting effect. The major contributions of this paper are the idea of using the importance distribution to control local shapes, the per-voxel accessory lights and the perceptual measurement. PMID- 26357299 TI - Improving the Efficiency of Viewpoint Composition. AB - In this paper, we concentrate on the problem of finding the viewpoint that best satisfies a set of visual composition properties, often referred to as Virtual Camera or Viewpoint Composition. Previous approaches in the literature, which are based on general optimization solvers, are limited in their practical applicability because of unsuitable computation times and limited experimental analysis. To bring performances much closer to the needs of interactive applications, we introduce novel ways to define visual properties, evaluate their satisfaction, and initialize the search for optimal viewpoints, and test them in several problems under various time budgets, quantifying also, for the first time in the domain, the importance of tuning the parameters that control the behavior of the solving process. While our solver, as others in the literature, is based on Particle Swarm Optimization, our contributions could be applied to any stochastic search process that solves through many viewpoint evaluations, such as the genetic algorithms employed by other papers in the literature. The complete source code of our approach, together with the scenes and problems we have employed, can be downloaded from https://bitbucket.org/rranon/smart-viewpoint computation-lib. PMID- 26357300 TI - Stroscope: Multi-Scale Visualization of Irregularly Measured Time-Series Data. AB - For irregularly measured time-series data, the measurement frequency or interval is as crucial information as measurements are. A well-known time-series visualization such as the line graph is good at showing an overall temporal pattern of change; however, it is not so effective in revealing the measurement frequency/interval while likely giving illusory confidence in values between measurements. In contrast, the bar graph is more effective in showing the frequency/interval, but less effective in showing an overall pattern than the line graph. We integrate the line graph and bar graph in a unified visualization model, called a ripple graph, to take the benefits of both of them with enhanced graphical integrity. Based on the ripple graph, we implemented an interactive time-series data visualization tool, called Stroscope, which facilitates multi scale visualizations by providing users with a graphical widget to interactively control the integrated visualization model. We evaluated the visualization model (i.e., the ripple graph) through a controlled user study and Stroscope through long-term case studies with neurologists exploring large blood pressure measurement data of stroke patients. Results from our evaluations demonstrate that the ripple graph outperforms existing time-series visualizations, and that Stroscope has the efficacy and potential as an effective visual analysis tool for (irregularly) measured time-series data. PMID- 26357301 TI - Model Estimation and Selection towards Unconstrained Real-Time Tracking and Mapping. AB - We present an approach and prototype implementation to initialization-free real time tracking and mapping that supports any type of camera motion in 3D environments, that is, parallax-inducing as well as rotation-only motions. Our approach effectively behaves like a keyframe-based Simultaneous Localization and Mapping system or a panorama tracking and mapping system, depending on the camera movement. It seamlessly switches between the two modes and is thus able to track and map through arbitrary sequences of parallax-inducing and rotation-only camera movements. The system integrates both model-based and model-free tracking, automatically choosing between the two depending on the situation, and subsequently uses the "Geometric Robust Information Criterion" to decide whether the current camera motion can best be represented as a parallax-inducing motion or a rotation-only motion. It continues to collect and map data after tracking failure by creating separate tracks which are later merged if they are found to overlap. This is in contrast to most existing tracking and mapping systems, which suspend tracking and mapping and thus discard valuable data until relocalization with respect to the initial map is successful. We tested our prototype implementation on a variety of video sequences, successfully tracking through different camera motions and fully automatically building combinations of panoramas and 3D structure. PMID- 26357302 TI - Kinectrack: 3D Pose Estimation Using a Projected Dense Dot Pattern. AB - Kinectrack is a novel approach to six-DoF tracking that provides agile real-time pose estimation using only commodity hardware. The dot pattern emitter and IR camera components of the standard Kinect device are separated to allow the emitter to roam freely relative to a fixed camera. The six-DoF pose of the emitter component is recovered by matching the dense dot pattern observed by the camera to a pre-captured reference image. A novel matching technique is introduced to obtain the dense dot pattern correspondences efficiently in wide- and adaptive-baseline scenarios that requires only a small subset of the full dense dot pattern to fall within the field of view of the fixed camera. An auto calibration process is proposed in order to obtain the intrinsic parameters of the fixed camera and the internal dot pattern reference image of the emitter. The system simultaneously recovers the six-DoF pose of the emitter device and the piecewise planar 3D scene structure. Kinectrack provides a low-cost method for tracking an object without any on-board computation, with small size and only simple electronics. This paper extends the original ISMAR 2012 submission, including a demonstration of robust pose tracking for AR and examples of matching in planar and non-planar scenes. PMID- 26357303 TI - Learning Optimized Local Difference Binaries for Scalable Augmented Reality on Mobile Devices. AB - The efficiency, robustness and distinctiveness of a feature descriptor are critical to the user experience and scalability of a mobile augmented reality (AR) system. However, existing descriptors are either too computationally expensive to achieve real-time performance on a mobile device such as a smartphone or tablet, or not sufficiently robust and distinctive to identify correct matches from a large database. As a result, current mobile AR systems still only have limited capabilities, which greatly restrict their deployment in practice. In this paper, we propose a highly efficient, robust and distinctive binary descriptor, called Learning-based Local Difference Binary (LLDB). LLDB directly computes a binary string for an image patch using simple intensity and gradient difference tests on pairwise grid cells within the patch. To select an optimized set of grid cell pairs, we densely sample grid cells from an image patch and then leverage a modified AdaBoost algorithm to automatically extract a small set of critical ones with the goal of maximizing the Hamming distance between mismatches while minimizing it between matches. Experimental results demonstrate that LLDB is extremely fast to compute and to match against a large database due to its high robustness and distinctiveness. Compared to the state-of the-art binary descriptors, primarily designed for speed, LLDB has similar efficiency for descriptor construction, while achieving a greater accuracy and faster matching speed when matching over a large database with 2.3M descriptors on mobile devices. PMID- 26357304 TI - High-Quality Real-Time Video Inpaintingwith PixMix. AB - While image inpainting has recently become widely available in image manipulation tools, existing approaches to video inpainting typically do not even achieve interactive frame rates yet as they are highly computationally expensive. Further, they either apply severe restrictions on the movement of the camera or do not provide a high-quality coherent video stream. In this paper we will present our approach to high-quality real-time capable image and video inpainting. Our PixMix approach even allows for the manipulation of live video streams, providing the basis for real Diminished Reality (DR) applications. We will show how our approach generates coherent video streams dealing with quite heterogeneous background environments and non-trivial camera movements, even applying constraints in real-time. PMID- 26357305 TI - Effects of Approximate Filtering on the Appearance of Bidirectional Texture Functions. AB - The BTF data structure was a breakthrough for appearance modeling in computer graphics. More research is needed though to make BTFs practical in rendering applications. We present the first systematic study of the effects of Approximate filtering on the appearance of BTFs, by exploring the spatial, angular and temporal domains over a varied set of stimuli. We perform our initial experiments on simple geometry and lighting, and verify our observations on more complex settings. We consider multi-dimensional filtering versus conventional mipmapping, and find that multi-dimensional filtering produces superior results. We examine the tradeoff between under- and oversampling, and find that different filtering strategies can be applied in each domain, while maintaining visual equivalence with respect to a ground truth. For example, we find that preserving contrast is more important in static than dynamic images, indicating greater levels of spatial filtering are possible for animations. We find that filtering can be performed more aggressively in the angular domain than in the spatial. Additionally, we find that high-level visual descriptors of the BTF are linked to the perceptual performance of pre-filtered approximations. In turn, some of these high-level descriptors correlate with low level statistics of the BTF. We show six different practical applications of applying our findings to improving filtering, rendering and compression strategies. PMID- 26357306 TI - Exploring the Spectrum of Dynamic Scheduling Algorithms for Scalable Distributed MemoryRay Tracing. AB - This paper extends and evaluates a family of dynamic ray scheduling algorithms that can be performed in-situ on large distributed memory parallel computers. The key idea is to consider both ray state and data accesses when scheduling ray computations. We compare three instances of this family of algorithms against two traditional statically scheduled schemes. We show that our dynamic scheduling approach can render data sets that are larger than aggregate system memory and that cannot be rendered by existing statically scheduled ray tracers. For smaller problems that fit in aggregate memory but are larger than typical shared memory, our dynamic approach is competitive with the best static scheduling algorithm. PMID- 26357307 TI - Importance Driven Environment Map Sampling. AB - In this paper we present an efficient method for supporting image based lighting (IBL) for bidirectional methods. This improves both sampling of the environment, and the detection and sampling of important regions of the scene, such as windows and doors. These parts of the scene often have a small area proportional to that of the entire scene, so paths which pass through them are generated with a low probability. The method proposed in this paper improves sampling efficiency, by taking into account view importance, and modifies the lighting distribution to use light transport information from the camera. This method automatically constructs a sampling distribution in locations which are relevant to the camera position, thereby improving sampling of light paths. This approach can be applied to several bidirectional rendering methods, and results are shown for bidirectional path tracing, metropolis light transport and progressive photon mapping. When compared to other methods, efficiency results demonstrate speed ups of orders of magnitude. PMID- 26357309 TI - The Perception of Visual UncertaintyRepresentation by Non-Experts. AB - We tested how non-experts judge point probability for seven different visual representations of uncertainty, using a case from an unfamiliar domain. Participants (n = 140) rated the probability that the boundary between two earth layers passed through a given point, for seven different visualizations of the positional uncertainty of the boundary. For all types of visualizations, most observers appear to construct an internal model of the uncertainty distribution that closely resembles a normal distribution. However, the visual form of the uncertainty range (i.e., the visualization type) affects this internal model and the internal model relates to participants' numeracy. We conclude that perceived certainty is affected by its visual representation. In a follow-up experiment we found no indications that the absence (or presence) of a prominent center line in the visualization affects the internal model. We discuss if and how our results inform which visual representation is most suitable for representing uncertainty and make suggestions for future work. PMID- 26357308 TI - Surface Meshing with Curvature Convergence. AB - Surface meshing plays a fundamental role in graphics and visualization. Many geometric processing tasks involve solving geometric PDEs on meshes. The numerical stability, convergence rates and approximation errors are largely determined by the mesh qualities. In practice, Delaunay refinement algorithms offer satisfactory solutions to high quality mesh generations. The theoretical proofs for volume based and surface based Delaunay refinement algorithms have been established, but those for conformal parameterization based ones remain wide open. This work focuses on the curvature measure convergence for the conformal parameterization based Delaunay refinement algorithms. Given a metric surface, the proposed approach triangulates its conformal uniformization domain by the planar Delaunay refinement algorithms, and produces a high quality mesh. We give explicit estimates for the Hausdorff distance, the normal deviation, and the differences in curvature measures between the surface and the mesh. In contrast to the conventional results based on volumetric Delaunay refinement, our stronger estimates are independent of the mesh structure and directly guarantee the convergence of curvature measures. Meanwhile, our result on Gaussian curvature measure is intrinsic to the Riemannian metric and independent of the embedding. In practice, our meshing algorithm is much easier to implement and much more efficient. The experimental results verified our theoretical results and demonstrated the efficiency of the meshing algorithm. PMID- 26357310 TI - Toward Evaluating the Usefulness of GlobalIllumination for Novices in Lighting Design Tasks. AB - Thanks to its ability to improve the realism of computer-generated imagery, the use of global illumination has recently become widespread among digital lighting artists. It remains unclear, though, what impact it has on the lighting design workflows, especially for novice users. In this paper we present a user study which investigates the use of global illumination, large area lights, and non physical fill lights in lighting design tasks, where 26 novice subjects design lighting with these tools. The collected data suggest that global illumination is not significantly harder to control for novice users that direct illumination, and when given the possibility, most users opt to use it in their designs. The use of global illumination together with large area lights leads to simpler lighting setups with fewer non-physical fill lights. Interestingly, global illumination does not supersede fill lights: users still include them into their globally illuminated lighting setups. We believe that our results will find use in the development of lighting design tools for non-expert users. PMID- 26357311 TI - Divide and Conquer Approach to Contact Map Overlap Problem Using 2D-Pattern Mining of Protein Contact Networks. AB - A novel approach to Contact Map Overlap (CMO) problem is proposed using the two dimensional clusters present in the contact maps. Each protein is represented as a set of the non-trivial clusters of contacts extracted from its contact map. The approach involves finding matching regions between the two contact maps using approximate 2D-pattern matching algorithm and dynamic programming technique. These matched pairs of small contact maps are submitted in parallel to a fast heuristic CMO algorithm. The approach facilitates parallelization at this level since all the pairs of contact maps can be submitted to the algorithm in parallel. Then, a merge algorithm is used in order to obtain the overall alignment. As a proof of concept, MSVNS, a heuristic CMO algorithm is used for global as well as local alignment. The divide and conquer approach is evaluated for two benchmark data sets that of Skolnick and Ding et al. It is interesting to note that along with achieving saving of time, better overlap is also obtained for certain protein folds. PMID- 26357312 TI - Biclustering with Flexible Plaid Models to Unravel Interactions between Biological Processes. AB - Genes can participate in multiple biological processes at a time and thus their expression can be seen as a composition of the contributions from the active processes. Biclustering under a plaid assumption allows the modeling of interactions between transcriptional modules or biclusters (subsets of genes with coherence across subsets of conditions) by assuming an additive composition of contributions in their overlapping areas. Despite the biological interest of plaid models, few biclustering algorithms consider plaid effects and, when they do, they place restrictions on the allowed types and structures of biclusters, and suffer from robustness problems by seizing exact additive matchings. We propose BiP (Biclustering using Plaid models), a biclustering algorithm with relaxations to allow expression levels to change in overlapping areas according to biologically meaningful assumptions (weighted and noise-tolerant composition of contributions). BiP can be used over existing biclustering solutions (seizing their benefits) as it is able to recover excluded areas due to unaccounted plaid effects and detect noisy areas non-explained by a plaid assumption, thus producing an explanatory model of overlapping transcriptional activity. Experiments on synthetic data support BiP's efficiency and effectiveness. The learned models from expression data unravel meaningful and non-trivial functional interactions between biological processes associated with putative regulatory modules. PMID- 26357313 TI - Unsupervised Structure Detection in Biomedical Data. AB - A major challenge in computational biology is to find simple representations of high-dimensional data that best reveal the underlying structure. In this work, we present an intuitive and easy-to-implement method based on ranked neighborhood comparisons that detects structure in unsupervised data. The method is based on ordering objects in terms of similarity and on the mutual overlap of nearest neighbors. This basic framework was originally introduced in the field of social network analysis to detect actor communities. We demonstrate that the same ideas can successfully be applied to biomedical data sets in order to reveal complex underlying structure. The algorithm is very efficient and works on distance data directly without requiring a vectorial embedding of data. Comprehensive experiments demonstrate the validity of this approach. Comparisons with state-of the-art clustering methods show that the presented method outperforms hierarchical methods as well as density based clustering methods and model-based clustering. A further advantage of the method is that it simultaneously provides a visualization of the data. Especially in biomedical applications, the visualization of data can be used as a first pre-processing step when analyzing real world data sets to get an intuition of the underlying data structure. We apply this model to synthetic data as well as to various biomedical data sets which demonstrate the high quality and usefulness of the inferred structure. PMID- 26357315 TI - An O(m log m)-Time Algorithm for Detecting Superbubbles. AB - In genome assembly graphs, motifs such as tips, bubbles, and cross links are studied in order to find sequencing errors and to understand the nature of the genome. Superbubble, a complex generalization of bubbles, was recently proposed as an important subgraph class for analyzing assembly graphs. At present, a quadratic time algorithm is known. This paper gives an O(m log m)-time algorithm to solve this problem for a graph with m edges. PMID- 26357314 TI - Randomized Subspace Learning for Proline Cis-Trans Isomerization Prediction. AB - Proline residues are common source of kinetic complications during folding. The X Pro peptide bond is the only peptide bond for which the stability of the cis and trans conformations is comparable. The cis-trans isomerization (CTI) of X-Pro peptide bonds is a widely recognized rate-limiting factor, which can not only induces additional slow phases in protein folding but also modifies the millisecond and sub-millisecond dynamics of the protein. An accurate computational prediction of proline CTI is of great importance for the understanding of protein folding, splicing, cell signaling, and transmembrane active transport in both the human body and animals. In our earlier work, we successfully developed a biophysically motivated proline CTI predictor utilizing a novel tree-based consensus model with a powerful metalearning technique and achieved 86.58 percent Q2 accuracy and 0.74 Mcc, which is a better result than the results (70-73 percent Q2 accuracies) reported in the literature on the well referenced benchmark dataset. In this paper, we describe experiments with novel randomized subspace learning and bootstrap seeding techniques as an extension to our earlier work, the consensus models as well as entropy-based learning methods, to obtain better accuracy through a precise and robust learning scheme for proline CTI prediction. PMID- 26357316 TI - An Efficient Search Algorithm for Finding Genomic-Range Overlaps Based on the Maximum Range Length. AB - Efficient search algorithms for finding genomic-range overlaps are essential for various bioinformatics applications. A majority of fast algorithms for searching the overlaps between a query range (e.g., a genomic variant) and a set of N reference ranges (e.g., exons) has time complexity of O(k + logN), where kdenotes a term related to the length and location of the reference ranges. Here, we present a simple but efficient algorithm that reduces k, based on the maximum reference range length. Specifically, for a given query range and the maximum reference range length, the proposed method divides the reference range set into three subsets: always, potentially, and never overlapping. Therefore, search effort can be reduced by excluding never overlapping subset. We demonstrate that the running time of the proposed algorithm is proportional to potentially overlapping subset size, that is proportional to the maximum reference range length if all the other conditions are the same. Moreover, an implementation of our algorithm was 13.8 to 30.0 percent faster than one of the fastest range search methods available when tested on various genomic-range data sets. The proposed algorithm has been incorporated into a disease-linked variant prioritization pipeline for WGS (http://gnome.tchlab.org) and its implementation is available at http://ml.ssu.ac.kr/gSearch. PMID- 26357317 TI - Curatable Named-Entity Recognition Using Semantic Relations. AB - Named-entity recognition (NER) plays an important role in the development of biomedical databases. However, the existing NER tools produce multifarious named entities which may result in both curatable and non-curatable markers. To facilitate biocuration with a straightforward approach, classifying curatable named-entities is helpful with regard to accelerating the biocuration workflow. Co-occurrence Interaction Nexus with Named-entity Recognition (CoINNER) is a web based tool that allows users to identify genes, chemicals, diseases, and action term mentions in the Comparative Toxicogenomic Database (CTD). To further discover interactions, CoINNER uses multiple advanced algorithms to recognize the mentions in the BioCreative IV CTD Track. CoINNER is developed based on a prototype system that annotated gene, chemical, and disease mentions in PubMed abstracts at BioCreative 2012 Track I (literature triage). We extended our previous system in developing CoINNER. The pre-tagging results of CoINNER were developed based on the state-of-the-art named entity recognition tools in BioCreative III. Next, a method based on conditional random fields (CRFs) is proposed to predict chemical and disease mentions in the articles. Finally, action term mentions were collected by latent Dirichlet allocation (LDA). At the BioCreative IV CTD Track, the best F-measures reached for gene/protein, chemical/drug and disease NER were 54 percent while CoINNER achieved a 61.5 percent F-measure. System URL: http://ikmbio.csie.ncku.edu.tw/coinner/ introduction.htm. PMID- 26357318 TI - ResSeq: Enhancing Short-Read Sequencing Alignment By Rescuing Error-Containing Reads. AB - Next-generation short-read sequencing is widely utilized in genomic studies. Biological applications require an alignment step to map sequencing reads to the reference genome, before acquiring expected genomic information. This requirement makes alignment accuracy a key factor for effective biological interpretation. Normally, when accounting for measurement errors and single nucleotide polymorphisms, short read mappings with a few mismatches are generally considered acceptable. However, to further improve the efficiency of short-read sequencing alignment, we propose a method to retrieve additional reliably aligned reads (reads with more than a pre-defined number of mismatches), using a Bayesian-based approach. In this method, we first retrieve the sequence context around the mismatched nucleotides within the already aligned reads; these loci contain the genomic features where sequencing errors occur. Then, using the derived pattern, we evaluate the remaining (typically discarded) reads with more than the allowed number of mismatches, and calculate a score that represents the probability that a specific alignment is correct. This strategy allows the extraction of more reliably aligned reads, therefore improving alignment sensitivity. IMPLEMENTATION: The source code of our tool, ResSeq, can be downloaded from: https://github.com/hrbeubiocenter/Resseq. PMID- 26357320 TI - Heterogeneous Compression of Large Collections of Evolutionary Trees. AB - Compressing heterogeneous collections of trees is an open problem in computational phylogenetics. In a heterogeneous tree collection, each tree can contain a unique set of taxa. An ideal compression method would allow for the efficient archival of large tree collections and enable scientists to identify common evolutionary relationships over disparate analyses. In this paper, we extend TreeZip to compress heterogeneous collections of trees. TreeZip is the most efficient algorithm for compressing homogeneous tree collections. To the best of our knowledge, no other domain-based compression algorithm exists for large heterogeneous tree collections or enable their rapid analysis. Our experimental results indicate that TreeZip averages 89.03 percent (72.69 percent) space savings on unweighted (weighted) collections of trees when the level of heterogeneity in a collection is moderate. The organization of the TRZ file allows for efficient computations over heterogeneous data. For example, consensus trees can be computed in mere seconds. Lastly, combining the TreeZip compressed (TRZ) file with general-purpose compression yields average space savings of 97.34 percent (81.43 percent) on unweighted (weighted) collections of trees. Our results lead us to believe that TreeZip will prove invaluable in the efficient archival of tree collections, and enables scientists to develop novel methods for relating heterogeneous collections of trees. PMID- 26357319 TI - MMBIRFinder: A Tool to Detect Microhomology-Mediated Break-Induced Replication. AB - The introduction of next-generation sequencing technologies has radically changed the way we view structural genetic events. Microhomology-mediated break-induced replication (MMBIR) is just one of the many mechanisms that can cause genomic destabilization that may lead to cancer. Although the mechanism for MMBIR remains unclear, it has been shown that MMBIR is typically associated with template switching events. Currently, to our knowledge, there is no existing bioinformatics tool to detect these template-switching events. We have developed MMBIRFinder, a method that detects template-switching events associated with MMBIR from whole-genome sequenced data. MMBIRFinder uses a half-read alignment approach to identify potential regions of interest. Clustering of these potential regions helps narrow the search space to regions with strong evidence. Subsequent local alignments identify the template-switching events with single-nucleotide accuracy. Using simulated data, MMBIRFinder identified 83 percent of the MMBIR regions within a five nucleotide tolerance. Using real data, MMBIRFinder identified 16 MMBIR regions on a normal breast tissue data sample and 51 MMBIR regions on a triple-negative breast cancer tumor sample resulting in detection of 37 novel template-switching events. Finally, we identified template-switching events residing in the promoter region of seven genes that have been implicated in breast cancer. PMID- 26357321 TI - ClusterViz: A Cytoscape APP for Cluster Analysis of Biological Network. AB - Cluster analysis of biological networks is one of the most important approaches for identifying functional modules and predicting protein functions. Furthermore, visualization of clustering results is crucial to uncover the structure of biological networks. In this paper, ClusterViz, an APP of Cytoscape 3 for cluster analysis and visualization, has been developed. In order to reduce complexity and enable extendibility for ClusterViz, we designed the architecture of ClusterViz based on the framework of Open Services Gateway Initiative. According to the architecture, the implementation of ClusterViz is partitioned into three modules including interface of ClusterViz, clustering algorithms and visualization and export. ClusterViz fascinates the comparison of the results of different algorithms to do further related analysis. Three commonly used clustering algorithms, FAG-EC, EAGLE and MCODE, are included in the current version. Due to adopting the abstract interface of algorithms in module of the clustering algorithms, more clustering algorithms can be included for the future use. To illustrate usability of ClusterViz, we provided three examples with detailed steps from the important scientific articles, which show that our tool has helped several research teams do their research work on the mechanism of the biological networks. PMID- 26357322 TI - Building Transcriptional Association Networks in Cytoscape with RegNetC. AB - The Regression Network plugin for Cytoscape (RegNetC) implements the RegNet algorithm for the inference of transcriptional association network from gene expression profiles. This algorithm is a model tree-based method to detect the relationship between each gene and the remaining genes simultaneously instead of analyzing individually each pair of genes as correlation-based methods do. Model trees are a very useful technique to estimate the gene expression value by regression models and favours localized similarities over more global similarity, which is one of the major drawbacks of correlation-based methods. Here, we present an integrated software suite, named RegNetC, as a Cytoscape plugin that can operate on its own as well. RegNetC facilitates, according to user-defined parameters, the resulted transcriptional gene association network in .sif format for visualization, analysis and interoperates with other Cytoscape plugins, which can be exported for publication figures. In addition to the network, the RegNetC plugin also provides the quantitative relationships between genes expression values of those genes involved in the inferred network, i.e., those defined by the regression models. PMID- 26357323 TI - iPFPi: A System for Improving Protein Function Prediction through Cumulative Iterations. AB - We propose a classifier system called iPFPi that predicts the functions of un annotated proteins. iPFPi assigns an un-annotated protein P the functions of GO annotation terms that are semantically similar to P. An un-annotated protein P and a GO annotation term T are represented by their characteristics. The characteristics of P are GO terms found within the abstracts of biomedical literature associated with P. The characteristics of Tare GO terms found within the abstracts of biomedical literature associated with the proteins annotated with the function of T. Let F and F/ be the important (dominant) sets of characteristic terms representing T and P, respectively. iPFPi would annotate P with the function of T, if F and F/ are semantically similar. We constructed a novel semantic similarity measure that takes into consideration several factors, such as the dominance degree of each characteristic term t in set F based on its score, which is a value that reflects the dominance status of t relative to other characteristic terms, using pairwise beats and looses procedure. Every time a protein P is annotated with the function of T, iPFPi updates and optimizes the current scores of the characteristic terms for T based on the weights of the characteristic terms for P. Set F will be updated accordingly. Thus, the accuracy of predicting the function of T as the function of subsequent proteins improves. This prediction accuracy keeps improving over time iteratively through the cumulative weights of the characteristic terms representing proteins that are successively annotated with the function of T. We evaluated the quality of iPFPi by comparing it experimentally with two recent protein function prediction systems. Results showed marked improvement. PMID- 26357324 TI - Software Suite for Gene and Protein Annotation Prediction and Similarity Search. AB - In the computational biology community, machine learning algorithms are key instruments for many applications, including the prediction of gene-functions based upon the available biomolecular annotations. Additionally, they may also be employed to compute similarity between genes or proteins. Here, we describe and discuss a software suite we developed to implement and make publicly available some of such prediction methods and a computational technique based upon Latent Semantic Indexing (LSI), which leverages both inferred and available annotations to search for semantically similar genes. The suite consists of three components. BioAnnotationPredictor is a computational software module to predict new gene functions based upon Singular Value Decomposition of available annotations. SimilBio is a Web module that leverages annotations available or predicted by BioAnnotationPredictor to discover similarities between genes via LSI. The suite includes also SemSim, a new Web service built upon these modules to allow accessing them programmatically. We integrated SemSim in the Bio Search Computing framework (http://www.bioinformatics.deib. polimi.it/bio-seco/seco/), where users can exploit the Search Computing technology to run multi-topic complex queries on multiple integrated Web services. Accordingly, researchers may obtain ranked answers involving the computation of the functional similarity between genes in support of biomedical knowledge discovery. PMID- 26357325 TI - Rapid Assessment of Adverse Drug Reactions by Statistical Solution of Gene Association Network. AB - Adverse drug reaction (ADR) is a common clinical problem, sometimes accompanying with high risk of mortality and morbidity. It is also one of the major factors that lead to failure in new drug development. Unfortunately, most of current experimental and computational methods are unable to evaluate clinical safety of drug candidates in early drug discovery stage due to the very limited knowledge of molecular mechanisms underlying ADRs. Therefore, in this study, we proposed a novel na?ive Bayesian model for rapid assessment of clinical ADRs with frequency estimation. This model was constructed on a gene-ADR association network, which covered 611 US FDA approved drugs, 14,251 genes, and 1,254 distinct ADR terms. An average detection rate of 99.86 and 99.73 percent were achieved eventually in identification of known ADRs in internal test data set and external case analyses respectively. Moreover, a comparative analysis between the estimated frequencies of ADRs and their observed frequencies was undertaken. It is observed that these two frequencies have the similar distribution trend. These results suggest that the naive Bayesian model based on gene-ADR association network can serve as an efficient and economic tool in rapid ADRs assessment. PMID- 26357326 TI - Quantitative Measurement of Split of the Second Heart Sound (S2). AB - This study proposes a quantitative measurement of split of the second heart sound (S2) based on nonstationary signal decomposition to deal with overlaps and energy modeling of the subcomponents of S2. The second heart sound includes aortic (A2) and pulmonic (P2) closure sounds. However, the split detection is obscured due to A2-P2 overlap and low energy of P2. To identify such split, HVD method is used to decompose the S2 into a number of components while preserving the phase information. Further, A2s and P2s are localized using smoothed pseudo Wigner Ville distribution followed by reassignment method. Finally, the split is calculated by taking the differences between the means of time indices of A2s and P2s. Experiments on total 33 clips of S2 signals are performed for evaluation of the method. The mean +/- standard deviation of the split is 34.7 +/- 4.6 ms. The method measures the split efficiently, even when A2-P2 overlap is <= 20 ms and the normalized peak temporal ratio of P2 to A2 is low (>= 0.22). This proposed method thus, demonstrates its robustness by defining split detectability (SDT), the split detection aptness through detecting P2s, by measuring up to 96 percent. Such findings reveal the effectiveness of the method as competent against the other baselines, especially for A2-P2 overlaps and low energy P2. PMID- 26357327 TI - An Optimized LMMSE Based Method for 3D MRI Denoising. AB - Post-acquisition denoising of magnetic resonance (MR) images is an important step to improve any quantitative measurement of the acquired data. In this paper, assuming a Rician noise model, a new filtering method based on the linear minimum mean square error (LMMSE) estimation is introduced, which employs the self similarity property of the MR data to restore the noise-less signal. This method takes into account the structural characteristics of images and the Bayesian mean square error (Bmse) of the estimator to address the denoising problem. In general, a twofold data processing approach is developed; first, the noisy MR data is processed using a patch-based L(2)-norm similarity measure to provide the primary set of samples required for the estimation process. Afterwards, the Bmse of the estimator is derived as the optimization function to analyze the pre selected samples and minimize the error between the estimated and the underlying signal. Compared to the LMMSE method and also its recently proposed SNR-adapted realization (SNLMMSE), the optimized way of choosing the samples together with the automatic adjustment of the filtering parameters lead to a more robust estimation performance with our approach. Experimental results show the competitive performance of the proposed method in comparison with related state of-the-art methods. PMID- 26357328 TI - RBioCloud: A Light-Weight Framework for Bioconductor and R-based Jobs on the Cloud. AB - Large-scale ad hoc analytics of genomic data is popular using the R-programming language supported by over 700 software packages provided by Bioconductor. More recently, analytical jobs are benefitting from on-demand computing and storage, their scalability and their low maintenance cost, all of which are offered by the cloud. While biologists and bioinformaticists can take an analytical job and execute it on their personal workstations, it remains challenging to seamlessly execute the job on the cloud infrastructure without extensive knowledge of the cloud dashboard. How analytical jobs can not only with minimum effort be executed on the cloud, but also how both the resources and data required by the job can be managed is explored in this paper. An open-source light-weight framework for executing R-scripts using Bioconductor packages, referred to as 'RBioCloud', is designed and developed. RBioCloud offers a set of simple command-line tools for managing the cloud resources, the data and the execution of the job. Three biological test cases validate the feasibility of RBioCloud. The framework is available from http://www.rbiocloud.com. PMID- 26357329 TI - A New Method for Detecting Protein Complexes based on the Three Node Cliques. AB - The identification of protein complexes in protein-protein interaction (PPI) networks is fundamental for understanding biological processes and cellular molecular mechanisms. Many graph computational algorithms have been proposed to identify protein complexes from PPI networks by detecting densely connected groups of proteins. These algorithms assess the density of subgraphs through evaluation of the sum of individual edges or nodes; thus, incomplete and inaccurate measures may miss meaningful biological protein complexes with functional significance. In this study, we propose a novel method for assessing the compactness of local subnetworks by measuring the number of three node cliques. The present method detects each optimal cluster by growing a seed and maximizing the compactness function. To demonstrate the efficacy of the new proposed method, we evaluate its performance using five PPI networks on three reference sets of yeast protein complexes with five different measurements and compare the performance of the proposed method with four state-of-the-art methods. The results show that the protein complexes generated by the proposed method are of better quality than those generated by four classic methods. Therefore, the new proposed method is effective and useful for detecting protein complexes in PPI networks. PMID- 26357330 TI - Adaptive Fuzzy Consensus Clustering Framework for Clustering Analysis of Cancer Data. AB - Performing clustering analysis is one of the important research topics in cancer discovery using gene expression profiles, which is crucial in facilitating the successful diagnosis and treatment of cancer. While there are quite a number of research works which perform tumor clustering, few of them considers how to incorporate fuzzy theory together with an optimization process into a consensus clustering framework to improve the performance of clustering analysis. In this paper, we first propose a random double clustering based cluster ensemble framework (RDCCE) to perform tumor clustering based on gene expression data. Specifically, RDCCE generates a set of representative features using a randomly selected clustering algorithm in the ensemble, and then assigns samples to their corresponding clusters based on the grouping results. In addition, we also introduce the random double clustering based fuzzy cluster ensemble framework (RDCFCE), which is designed to improve the performance of RDCCE by integrating the newly proposed fuzzy extension model into the ensemble framework. RDCFCE adopts the normalized cut algorithm as the consensus function to summarize the fuzzy matrices generated by the fuzzy extension models, partition the consensus matrix, and obtain the final result. Finally, adaptive RDCFCE (A-RDCFCE) is proposed to optimize RDCFCE and improve the performance of RDCFCE further by adopting a self-evolutionary process (SEPP) for the parameter set. Experiments on real cancer gene expression profiles indicate that RDCFCE and A-RDCFCE works well on these data sets, and outperform most of the state-of-the-art tumor clustering algorithms. PMID- 26357331 TI - An Integrated Framework for Functional Annotation of Protein Structural Domains. AB - Structural domains are evolutionary and functional units of proteins and play a critical role in comparative and functional genomics. Computational assignment of domain function with high reliability is essential for understanding whole protein functions. However, functional annotations are conventionally assigned onto full-length proteins rather than associating specific functions to the individual structural domains. In this article, we present Structural Domain Annotation (SDA), a novel computational approach to predict functions for SCOP structural domains. The SDA method integrates heterogeneous information sources, including structure alignment based protein-SCOP mapping features, InterPro2GO mapping information, PSSM Profiles, and sequence neighborhood features, with a Bayesian network. By large-scale annotating Gene Ontology terms to SCOP domains with SDA, we obtained a database of SCOP domain to Gene Ontology mappings, which contains ~162,000 out of the approximately 166,900 domains in SCOPe 2.03 (>97 percent) and their predicted Gene Ontology functions. We have benchmarked SDA using a single-domain protein dataset and an independent dataset from different species. Comparative studies show that SDA significantly outperforms the existing function prediction methods for structural domains in terms of coverage and maximum F-measure. PMID- 26357332 TI - Bayesian Normalization Model for Label-Free Quantitative Analysis by LC-MS. AB - We introduce a new method for normalization of data acquired by liquid chromatography coupled with mass spectrometry (LC-MS) in label-free differential expression analysis. Normalization of LC-MS data is desired prior to subsequent statistical analysis to adjust variabilities in ion intensities that are not caused by biological differences but experimental bias. There are different sources of bias including variabilities during sample collection and sample storage, poor experimental design, noise, etc. In addition, instrument variability in experiments involving a large number of LC-MS runs leads to a significant drift in intensity measurements. Although various methods have been proposed for normalization of LC-MS data, there is no universally applicable approach. In this paper, we propose a Bayesian normalization model (BNM) that utilizes scan-level information from LC-MS data. Specifically, the proposed method uses peak shapes to model the scan-level data acquired from extracted ion chromatograms (EIC) with parameters considered as a linear mixed effects model. We extended the model into BNM with drift (BNMD) to compensate for the variability in intensity measurements due to long LC-MS runs. We evaluated the performance of our method using synthetic and experimental data. In comparison with several existing methods, the proposed BNM and BNMD yielded significant improvement. PMID- 26357333 TI - Integrative Data Analysis of Multi-Platform Cancer Data with a Multimodal Deep Learning Approach. AB - Identification of cancer subtypes plays an important role in revealing useful insights into disease pathogenesis and advancing personalized therapy. The recent development of high-throughput sequencing technologies has enabled the rapid collection of multi-platform genomic data (e.g., gene expression, miRNA expression, and DNA methylation) for the same set of tumor samples. Although numerous integrative clustering approaches have been developed to analyze cancer data, few of them are particularly designed to exploit both deep intrinsic statistical properties of each input modality and complex cross-modality correlations among multi-platform input data. In this paper, we propose a new machine learning model, called multimodal deep belief network (DBN), to cluster cancer patients from multi-platform observation data. In our integrative clustering framework, relationships among inherent features of each single modality are first encoded into multiple layers of hidden variables, and then a joint latent model is employed to fuse common features derived from multiple input modalities. A practical learning algorithm, called contrastive divergence (CD), is applied to infer the parameters of our multimodal DBN model in an unsupervised manner. Tests on two available cancer datasets show that our integrative data analysis approach can effectively extract a unified representation of latent features to capture both intra- and cross-modality correlations, and identify meaningful disease subtypes from multi-platform cancer data. In addition, our approach can identify key genes and miRNAs that may play distinct roles in the pathogenesis of different cancer subtypes. Among those key miRNAs, we found that the expression level of miR-29a is highly correlated with survival time in ovarian cancer patients. These results indicate that our multimodal DBN based data analysis approach may have practical applications in cancer pathogenesis studies and provide useful guidelines for personalized cancer therapy. PMID- 26357334 TI - Optimal Experimental Design for Gene Regulatory Networks in the Presence of Uncertainty. AB - Of major interest to translational genomics is the intervention in gene regulatory networks (GRNs) to affect cell behavior; in particular, to alter pathological phenotypes. Owing to the complexity of GRNs, accurate network inference is practically challenging and GRN models often contain considerable amounts of uncertainty. Considering the cost and time required for conducting biological experiments, it is desirable to have a systematic method for prioritizing potential experiments so that an experiment can be chosen to optimally reduce network uncertainty. Moreover, from a translational perspective it is crucial that GRN uncertainty be quantified and reduced in a manner that pertains to the operational cost that it induces, such as the cost of network intervention. In this work, we utilize the concept of mean objective cost of uncertainty (MOCU) to propose a novel framework for optimal experimental design. In the proposed framework, potential experiments are prioritized based on the MOCU expected to remain after conducting the experiment. Based on this prioritization, one can select an optimal experiment with the largest potential to reduce the pertinent uncertainty present in the current network model. We demonstrate the effectiveness of the proposed method via extensive simulations based on synthetic and real gene regulatory networks. PMID- 26357335 TI - Statistical Detection of Intrinsically Multivariate Predictive Genes. AB - Canalizing genes possess broad regulatory power over a wide swath of regulatory processes. On the other hand, it has been hypothesized that the phenomenon of intrinsically multivariate prediction (IMP) is associated with canalization. However, applications have relied on user-selectable thresholds on the IMP score to decide on the presence of IMP. A methodology is developed here that avoids arbitrary thresholds, by providing a statistical test for the IMP score. In addition, the proposed procedure allows the incorporation of prior knowledge if available, which can alleviate the problem of loss of power due to small sample sizes. The issue of multiplicity of tests is addressed by family-wise error rate (FWER) and false discovery rate (FDR) controlling approaches. The proposed methodology is demonstrated by experiments using synthetic and real gene expression data from studies on melanoma and ionizing radiation (IR) responsive genes. The results with the real data identified DUSP1 and p53, two well-known canalizing genes associated with melanoma and IR response, respectively, as the genes with a clear majority of IMP predictor pairs. This validates the potential of the proposed methodology as a tool for discovery of canalizing genes from binary gene-expression data. The procedure is made available through an R package. PMID- 26357336 TI - RPCA-Based Tumor Classification Using Gene Expression Data. AB - Microarray techniques have been used to delineate cancer groups or to identify candidate genes for cancer prognosis. As such problems can be viewed as classification ones, various classification methods have been applied to analyze or interpret gene expression data. In this paper, we propose a novel method based on robust principal component analysis (RPCA) to classify tumor samples of gene expression data. Firstly, RPCA is utilized to highlight the characteristic genes associated with a special biological process. Then, RPCA and RPCA+LDA (robust principal component analysis and linear discriminant analysis) are used to identify the features. Finally, support vector machine (SVM) is applied to classify the tumor samples of gene expression data based on the identified features. Experiments on seven data sets demonstrate that our methods are effective and feasible for tumor classification. PMID- 26357337 TI - Automatic Analysis of Facial Affect: A Survey of Registration, Representation, and Recognition. AB - Automatic affect analysis has attracted great interest in various contexts including the recognition of action units and basic or non-basic emotions. In spite of major efforts, there are several open questions on what the important cues to interpret facial expressions are and how to encode them. In this paper, we review the progress across a range of affect recognition applications to shed light on these fundamental questions. We analyse the state-of-the-art solutions by decomposing their pipelines into fundamental components, namely face registration, representation, dimensionality reduction and recognition. We discuss the role of these components and highlight the models and new trends that are followed in their design. Moreover, we provide a comprehensive analysis of facial representations by uncovering their advantages and limitations; we elaborate on the type of information they encode and discuss how they deal with the key challenges of illumination variations, registration errors, head-pose variations, occlusions, and identity bias. This survey allows us to identify open issues and to define future directions for designing real-world affect recognition systems. PMID- 26357338 TI - Beyond the Sum of Parts: Voting with Groups of Dependent Entities. AB - The high complexity of multi-scale, category-level object detection in cluttered scenes is efficiently handled by Hough voting methods. However, the main shortcoming of the approach is that mutually dependent local observations are independently casting their votes for intrinsically global object properties such as object scale. Object hypotheses are then assumed to be a mere sum of their part votes. Popular representation schemes are, however, based on a dense sampling of semi-local image features, which are consequently mutually dependent. We take advantage of part dependencies and incorporate them into probabilistic Hough voting by deriving an objective function that connects three intimately related problems: i) grouping mutually dependent parts, ii) solving the correspondence problem conjointly for dependent parts, and iii) finding concerted object hypotheses using extended groups rather than based on local observations alone. Early commitments are avoided by not restricting parts to only a single vote for a locally best correspondence and we learn a weighting of parts during training to reflect their differing relevance for an object. Experiments successfully demonstrate the benefit of incorporating part dependencies through grouping into Hough voting. The joint optimization of groupings, correspondences, and votes not only improves the detection accuracy over standard Hough voting and a sliding window baseline, but it also reduces the computational complexity by significantly decreasing the number of candidate hypotheses. PMID- 26357339 TI - Demographic Estimation from Face Images: Human vs. Machine Performance. AB - Demographic estimation entails automatic estimation of age, gender and race of a person from his face image, which has many potential applications ranging from forensics to social media. Automatic demographic estimation, particularly age estimation, remains a challenging problem because persons belonging to the same demographic group can be vastly different in their facial appearances due to intrinsic and extrinsic factors. In this paper, we present a generic framework for automatic demographic (age, gender and race) estimation. Given a face image, we first extract demographic informative features via a boosting algorithm, and then employ a hierarchical approach consisting of between-group classification, and within-group regression. Quality assessment is also developed to identify low quality face images that are difficult to obtain reliable demographic estimates. Experimental results on a diverse set of face image databases, FG-NET (1K images), FERET (3K images), MORPH II (75K images), PCSO (100K images), and a subset of LFW (4K images), show that the proposed approach has superior performance compared to the state of the art. Finally, we use crowdsourcing to study the human perception ability of estimating demographics from face images. A side-by-side comparison of the demographic estimates from crowdsourced data and the proposed algorithm provides a number of insights into this challenging problem. PMID- 26357340 TI - Directed Connected Operators: Asymmetric Hierarchies for Image Filtering and Segmentation. AB - Connected operators provide well-established solutions for digital image processing, typically in conjunction with hierarchical schemes. In graph-based frameworks, such operators basically rely on symmetric adjacency relations between pixels. In this article, we introduce a notion of directed connected operators for hierarchical image processing, by also considering non-symmetric adjacency relations. The induced image representation models are no longer partition hierarchies (i.e., trees), but directed acyclic graphs that generalize standard morphological tree structures such as component trees, binary partition trees or hierarchical watersheds. We describe how to efficiently build and handle these richer data structures, and we illustrate the versatility of the proposed framework in image filtering and image segmentation. PMID- 26357341 TI - Free-Form Region Description with Second-Order Pooling. AB - Semantic segmentation and object detection are nowadays dominated by methods operating on regions obtained as a result of a bottom-up grouping process (segmentation) but use feature extractors developed for recognition on fixed-form (e.g. rectangular) patches, with full images as a special case. This is most likely suboptimal. In this paper we focus on feature extraction and description over free-form regions and study the relationship with their fixed-form counterparts. Our main contributions are novel pooling techniques that capture the second-order statistics of local descriptors inside such free-form regions. We introduce second-order generalizations of average and max-pooling that together with appropriate non-linearities, derived from the mathematical structure of their embedding space, lead to state-of-the-art recognition performance in semantic segmentation experiments without any type of local feature coding. In contrast, we show that codebook-based local feature coding is more important when feature extraction is constrained to operate over regions that include both foreground and large portions of the background, as typical in image classification settings, whereas for high-accuracy localization setups, second-order pooling over free-form regions produces results superior to those of the winning systems in the contemporary semantic segmentation challenges, with models that are much faster in both training and testing. PMID- 26357342 TI - Learning 3D Object Templates by Quantizing Geometry and Appearance Spaces. AB - While 3D object-centered shape-based models are appealing in comparison with 2D viewer-centered appearance-based models for their lower model complexities and potentially better view generalizabilities, the learning and inference of 3D models has been much less studied in the recent literature due to two factors: i) the enormous complexities of 3D shapes in geometric space; and ii) the gap between 3D shapes and their appearances in images. This paper aims at tackling the two problems by studying an And-Or Tree (AoT) representation that consists of two parts: i) a geometry-AoT quantizing the geometry space, i.e. the possible compositions of 3D volumetric parts and 2D surfaces within the volumes; and ii) an appearance-AoT quantizing the appearance space, i.e. the appearance variations of those shapes in different views. In this AoT, an And-node decomposes an entity into constituent parts, and an Or-node represents alternative ways of decompositions. Thus it can express a combinatorial number of geometry and appearance configurations through small dictionaries of 3D shape primitives and 2D image primitives. In the quantized space, the problem of learning a 3D object template is transformed to a structure search problem which can be efficiently solved in a dynamic programming algorithm by maximizing the information gain. We focus on learning 3D car templates from the AoT and collect a new car dataset featuring more diverse views. The learned car templates integrate both the shape based model and the appearance-based model to combine the benefits of both. In experiments, we show three aspects: 1) the AoT is more efficient than the frequently used octree method in space representation; 2) the learned 3D car template matches the state-of-the art performances on car detection and pose estimation in a public multi-view car dataset; and 3) in our new dataset, the learned 3D template solves the joint task of simultaneous object detection, pose/view estimation, and part localization. It can generalize over unseen views and performs better than the version 5 of the DPM model in terms of object detection and semantic part localization. PMID- 26357343 TI - Relative Hidden Markov Models for Video-Based Evaluation of Motion Skills in Surgical Training. AB - A proper temporal model is essential to analysis tasks involving sequential data. In computer-assisted surgical training, which is the focus of this study, obtaining accurate temporal models is a key step towards automated skill-rating. Conventional learning approaches can have only limited success in this domain due to insufficient amount of data with accurate labels. We propose a novel formulation termed Relative Hidden Markov Model and develop algorithms for obtaining a solution under this formulation. The method requires only relative ranking between input pairs, which are readily available from training sessions in the target application, hence alleviating the requirement on data labeling. The proposed algorithm learns a model from the training data so that the attribute under consideration is linked to the likelihood of the input, hence supporting comparing new sequences. For evaluation, synthetic data are first used to assess the performance of the approach, and then we experiment with real videos from a widely-adopted surgical training platform. Experimental results suggest that the proposed approach provides a promising solution to video-based motion skill evaluation. To further illustrate the potential of generalizing the method to other applications of temporal analysis, we also report experiments on using our model on speech-based emotion recognition. PMID- 26357344 TI - Robust High Dynamic Range Imaging by Rank Minimization. AB - This paper introduces a new high dynamic range (HDR) imaging algorithm which utilizes rank minimization. Assuming a camera responses linearly to scene radiance, the input low dynamic range (LDR) images captured with different exposure time exhibit a linear dependency and form a rank-1 matrix when stacking intensity of each corresponding pixel together. In practice, misalignments caused by camera motion, presences of moving objects, saturations and image noise break the rank-1 structure of the LDR images. To address these problems, we present a rank minimization algorithm which simultaneously aligns LDR images and detects outliers for robust HDR generation. We evaluate the performances of our algorithm systematically using synthetic examples and qualitatively compare our results with results from the state-of-the-art HDR algorithms using challenging real world examples. PMID- 26357345 TI - Structuring Lecture Videos by Automatic Projection Screen Localization and Analysis. AB - We present a fully automatic system for extracting the semantic structure of a typical academic presentation video, which captures the whole presentation stage with abundant camera motions such as panning, tilting, and zooming. Our system automatically detects and tracks both the projection screen and the presenter whenever they are visible in the video. By analyzing the image content of the tracked screen region, our system is able to detect slide progressions and extract a high-quality, non-occluded, geometrically-compensated image for each slide, resulting in a list of representative images that reconstruct the main presentation structure. Afterwards, our system recognizes text content and extracts keywords from the slides, which can be used for keyword-based video retrieval and browsing. Experimental results show that our system is able to generate more stable and accurate screen localization results than commonly-used object tracking methods. Our system also extracts more accurate presentation structures than general video summarization methods, for this specific type of video. PMID- 26357346 TI - The Inverted Multi-Index. AB - A new data structure for efficient similarity search in very large datasets of high-dimensional vectors is introduced. This structure called the inverted multi index generalizes the inverted index idea by replacing the standard quantization within inverted indices with product quantization. For very similar retrieval complexity and pre-processing time, inverted multi-indices achieve a much denser subdivision of the search space compared to inverted indices, while retaining their memory efficiency. Our experiments with large datasets of SIFT and GIST vectors demonstrate that because of the denser subdivision, inverted multi indices are able to return much shorter candidate lists with higher recall. Augmented with a suitable reranking procedure, multi-indices were able to significantly improve the speed of approximate nearest neighbor search on the dataset of 1 billion SIFT vectors compared to the best previously published systems, while achieving better recall and incurring only few percent of memory overhead. PMID- 26357347 TI - The Potential Energy of an Autoencoder. AB - Autoencoders are popular feature learning models, that are conceptually simple, easy to train and allow for efficient inference. Recent work has shown how certain autoencoders can be associated with an energy landscape, akin to negative log-probability in a probabilistic model, which measures how well the autoencoder can represent regions in the input space. The energy landscape has been commonly inferred heuristically, by using a training criterion that relates the autoencoder to a probabilistic model such as a Restricted Boltzmann Machine (RBM). In this paper we show how most common autoencoders are naturally associated with an energy function, independent of the training procedure, and that the energy landscape can be inferred analytically by integrating the reconstruction function of the autoencoder. For autoencoders with sigmoid hidden units, the energy function is identical to the free energy of an RBM, which helps shed light onto the relationship between these two types of model. We also show that the autoencoder energy function allows us to explain common regularization procedures, such as contractive training, from the perspective of dynamical systems. As a practical application of the energy function, a generative classifier based on class-specific autoencoders is presented. PMID- 26357348 TI - What Can Pictures Tell Us About Web Pages? Improving Document Search Using Images. AB - Traditional Web search engines do not use the images in the HTML pages to find relevant documents for a given query. Instead, they typically operate by computing a measure of agreement between the keywords provided by the user and only the text portion of each page. In this paper we study whether the content of the pictures appearing in a Web page can be used to enrich the semantic description of an HTML document and consequently boost the performance of a keyword-based search engine. We present a Web-scalable system that exploits a pure text-based search engine to find an initial set of candidate documents for a given query. Then, the candidate set is reranked using visual information extracted from the images contained in the pages. The resulting system retains the computational efficiency of traditional text-based search engines with only a small additional storage cost needed to encode the visual information. We test our approach on one of the TREC Million Query Track benchmarks where we show that the exploitation of visual content yields improvement in accuracies for two distinct text-based search engines, including the system with the best reported performance on this benchmark. We further validate our approach by collecting document relevance judgements on our search results using Amazon Mechanical Turk. The results of this experiment confirm the improvement in accuracy produced by our image-based reranker over a pure text-based system. PMID- 26357349 TI - Why Does Mutual-Information Work for Image Registration? A Deterministic Explanation. AB - This paper proposes a deterministic explanation for mutual-information-based image registration (MI registration). The explanation is that MI registration works because it aligns certain image partitions. This notion of aligning partitions is new, and is shown to be related to Schur- and quasi-convexity. The partition-alignment theory of this paper goes beyond explaining mutual- information. It suggests other objective functions for registering images. Some of these newer objective functions are not entropy-based. Simulations with noisy images show that the newer objective functions work well for registration, lending support to the theory. The theory proposed in this paper opens a number of directions for further research in image registration. These directions are also discussed. PMID- 26357350 TI - A Very Simple Safe-Bayesian Random Forest. AB - Random forests works by averaging several predictions of de-correlated trees. We show a conceptually radical approach to generate a random forest: random sampling of many trees from a prior distribution, and subsequently performing a weighted ensemble of predictive probabilities. Our approach uses priors that allow sampling of decision trees even before looking at the data, and a power likelihood that explores the space spanned by combination of decision trees. While each tree performs Bayesian inference to compute its predictions, our aggregation procedure uses the power likelihood rather than the likelihood and is therefore strictly speaking not Bayesian. Nonetheless, we refer to it as a Bayesian random forest but with a built-in safety. The safeness comes as it has good predictive performance even if the underlying probabilistic model is wrong. We demonstrate empirically that our Safe-Bayesian random forest outperforms MCMC or SMC based Bayesian decision trees in term of speed and accuracy, and achieves competitive performance to entropy or Gini optimised random forest, yet is very simple to construct. PMID- 26357351 TI - Efficient and Robust Specular Highlight Removal. AB - A robust and effective specular highlight removal method is proposed in this paper. It is based on a key observation--the maximum fraction of the diffuse colour component in diffuse local patches in colour images changes smoothly. The specular pixels can thus be treated as noise in this case. This property allows the specular highlights to be removed in an image denoising fashion: an edge preserving low-pass filter (e.g., the bilateral filter) can be used to smooth the maximum fraction of the colour components of the original image to remove the noise contributed by the specular pixels. Recent developments in fast bilateral filtering techniques enable the proposed method to run over 200* faster than state-of-the-art techniques on a standard CPU and differentiates it from previous work. PMID- 26357352 TI - From Pixels to Response Maps: Discriminative Image Filtering for Face Alignment in the Wild. AB - We propose a face alignment framework that relies on the texture model generated by the responses of discriminatively trained part-based filters. Unlike standard texture models built from pixel intensities or responses generated by generic filters (e.g. Gabor), our framework has two important advantages. First, by virtue of discriminative training, invariance to external variations (like identity, pose, illumination and expression) is achieved. Second, we show that the responses generated by discriminatively trained filters (or patch-experts) are sparse and can be modeled using a very small number of parameters. As a result, the optimization methods based on the proposed texture model can better cope with unseen variations. We illustrate this point by formulating both part based and holistic approaches for generic face alignment and show that our framework outperforms the state-of-the-art on multiple "wild" databases. The code and dataset annotations are available for research purposes from http://ibug.doc.ic.ac.uk/resources. PMID- 26357353 TI - WYSIWYG Stereo Paintingwith Usability Enhancements. AB - Despite increasing popularity of stereo capture and display systems, creating stereo artwork remains a challenge. This paper presents a stereo painting system, which enables effective from-scratch creation of high-quality stereo artwork. A key concept of our system is a stereo layer, which is composed of two RGBAd (RGBA + depth) buffers. Stereo layers alleviate the need for fully formed representational 3D geometry required by most existing 3D painting systems, and allow for simple, essential depth specification. RGBAd buffers also provide scalability for complex scenes by minimizing the dependency of stereo painting updates on the scene complexity. For interaction with stereo layers, we present stereo paint and stereo depth brushes, which manipulate the photometric (RGBA) and depth buffers of a stereo layer, respectively. In our system, painting and depth manipulation operations can be performed in arbitrary order with real-time visual feedback, providing a flexible WYSIWYG workflow for stereo painting. Our data structures allow for easy interoperability with existing image and geometry data, enabling a number of applications beyond from-scratch art creation, such as stereo conversion of monoscopic artwork and mixed-media art. Comments from artists and experimental results demonstrate that our system effectively aides in the creation of compelling stereo paintings. PMID- 26357354 TI - Interactive Mesostructures withVolumetric Collisions. AB - This paper presents a technique for interactively colliding with and deforming mesostructures at a per-texel level. It is compatible with a broad range of existing mesostructure rendering techniques including both safe and unsafe ray height field intersection algorithms. This technique is able to replace traditional 3D geometrical deformations (vertex-based) with 2D image space operations (pixel-based) that are parallelized on a GPU without CPU-GPU data shuffling and integrates well with existing physics engines. Additionally, surface and material properties may be specified at a per-texel level enabling a mesostructure to possess varying attributes intrinsic to its surface and collision behavior. Furthermore, this approach may replace traditional decals with image-based operations that naturally accumulate deformations without inserting any new geometry. This technique provides a simple and efficient way to make almost every surface in a virtual world responsive to user actions and events. It requires no preprocessing time and storage requirements of one additional texture or less. The algorithm uses existing inverse displacement map algorithms as well as existing physics engines and can be easily incorporated into new or existing game pipelines. PMID- 26357355 TI - Property and Lighting Manipulations for Static Volume Stylization Using a Painting Metaphor. AB - Although volumetric phenomena are important for realistic rendering and can even be a crucial component in the image, the artistic control of the volume's appearance is challenging. Appropriate tools to edit volume properties are missing, which can make it necessary to use simulation results directly. Alternatively, high-level modifications that are rarely intuitive, e.g., the tweaking of noise function parameters, can be utilized. Our work introduces a solution to stylize single-scattering volumetric effects in static volumes. Hereby, an artistic and intuitive control of emission, scattering and extinction becomes possible, while ensuring a smooth and coherent appearance when changing the viewpoint. Our method is based on tomographic reconstruction, which we link to the volumetric rendering equation. It analyzes a number of target views provided by the artist and adapts the volume properties to match the appearance for the given perspectives. Additionally, we describe how we can optimize for the environmental lighting to match a desired scene appearance, while keeping volume properties constant. Finally, both techniques can be combined. We demonstrate several use cases of our approach and illustrate its effectiveness. PMID- 26357356 TI - Filtering Non-Linear Transfer Functions on Surfaces. AB - Applying non-linear transfer functions and look-up tables to procedural functions (such as noise), surface attributes, or even surface geometry are common strategies used to enhance visual detail. Their simplicity and ability to mimic a wide range of realistic appearances have led to their adoption in many rendering problems. As with any textured or geometric detail, proper filtering is needed to reduce aliasing when viewed across a range of distances, but accurate and efficient transfer function filtering remains an open problem for several reasons: transfer functions are complex and non-linear, especially when mapped through procedural noise and/or geometry-dependent functions, and the effects of perspective and masking further complicate the filtering over a pixel's footprint. We accurately solve this problem by computing and sampling from specialized filtering distributions on the fly, yielding very fast performance. We investigate the case where the transfer function to filter is a color map applied to (macroscale) surface textures (like noise), as well as color maps applied according to (microscale) geometric details. We introduce a novel representation of a (potentially modulated) color map's distribution over pixel footprints using Gaussian statistics and, in the more complex case of high resolution color mapped microsurface details, our filtering is view- and light dependent, and capable of correctly handling masking and occlusion effects. Our approach can be generalized to filter other physical-based rendering quantities. We propose an application to shading with irradiance environment maps over large terrains. Our framework is also compatible with the case of transfer functions used to warp surface geometry, as long as the transformations can be represented with Gaussian statistics, leading to proper view- and light-dependent filtering results. Our results match ground truth and our solution is well suited to real time applications, requires only a few lines of shader code (provided in supplemental material, which can be found on the Computer Society Digital Library at http://doi.ieeecomputersociety.org/10.1109/TVCG.2013.102), is high performance, and has a negligible memory footprint. PMID- 26357357 TI - Translucent Radiosity: Efficiently Combining Diffuse Inter-Reflection and Subsurface Scattering. AB - It is hard to efficiently model the light transport in scenes with translucent objects for interactive applications. The inter-reflection between objects and their environments and the subsurface scattering through the materials intertwine to produce visual effects like color bleeding, light glows, and soft shading. Monte-Carlo based approaches have demonstrated impressive results but are computationally expensive, and faster approaches model either only inter reflection or only subsurface scattering. In this paper, we present a simple analytic model that combines diffuse inter-reflection and isotropic subsurface scattering. Our approach extends the classical work in radiosity by including a subsurface scattering matrix that operates in conjunction with the traditional form factor matrix. This subsurface scattering matrix can be constructed using analytic, measurement-based or simulation-based models and can capture both homogeneous and heterogeneous translucencies. Using a fast iterative solution to radiosity, we demonstrate scene relighting and dynamically varying object translucencies at near interactive rates. PMID- 26357358 TI - Hybrid Long-Range Collision Avoidance for Crowd Simulation. AB - Local collision avoidance algorithms in crowd simulation often ignore agents beyond a neighborhood of a certain size. This cutoff can result in sharp changes in trajectory when large groups of agents enter or exit these neighborhoods. In this work, we exploit the insight that exact collision avoidance is not necessary between agents at such large distances, and propose a novel algorithm for extending existing collision avoidance algorithms to perform approximate, long range collision avoidance. Our formulation performs long-range collision avoidance for distant agent groups to efficiently compute trajectories that are smoother than those obtained with state-of-the-art techniques and at faster rates. Comparison to real-world data demonstrates that crowds simulated with our algorithm exhibit an improved speed sensitivity to density similar to human crowds. Another issue often sidestepped in existing work is that discrete and continuum collision avoidance algorithms have different regions of applicability. For example, low-density crowds cannot be modeled as a continuum, while high density crowds can be expensive to model using discrete methods. We formulate a hybrid technique for crowd simulation which can accurately and efficiently simulate crowds at any density with seamless transitions between continuum and discrete representations. Our approach blends results from continuum and discrete algorithms, based on local density and velocity variance. In addition to being robust across a variety of group scenarios, it is also highly efficient, running at interactive rates for thousands of agents on portable systems. PMID- 26357359 TI - ADAPT: The Agent Development and Prototyping Testbed. AB - We present ADAPT, a flexible platform for designing and authoring functional, purposeful human characters in a rich virtual environment. Our framework incorporates character animation, navigation, and behavior with modular interchangeable components to produce narrative scenes. The animation system provides locomotion, reaching, gaze tracking, gesturing, sitting, and reactions to external physical forces, and can easily be extended with more functionality due to a decoupled, modular structure. The navigation component allows characters to maneuver through a complex environment with predictive steering for dynamic obstacle avoidance. Finally, our behavior framework allows a user to fully leverage a character's animation and navigation capabilities when authoring both individual decision-making and complex interactions between actors using a centralized, event-driven model. PMID- 26357360 TI - Large-Scale Overlays and Trends: Visually Mining, Panning and Zooming the Observable Universe. AB - We introduce a web-based computing infrastructure to assist the visual integration, mining and interactive navigation of large-scale astronomy observations. Following an analysis of the application domain, we design a client server architecture to fetch distributed image data and to partition local data into a spatial index structure that allows prefix-matching of spatial objects. In conjunction with hardware-accelerated pixel-based overlays and an online cross registration pipeline, this approach allows the fetching, displaying, panning and zooming of gigabit panoramas of the sky in real time. To further facilitate the integration and mining of spatial and non-spatial data, we introduce interactive trend images-compact visual representations for identifying outlier objects and for studying trends within large collections of spatial objects of a given class. In a demonstration, images from three sky surveys (SDSS, FIRST and simulated LSST results) are cross-registered and integrated as overlays, allowing cross-spectrum analysis of astronomy observations. Trend images are interactively generated from catalog data and used to visually mine astronomy observations of similar type. The front-end of the infrastructure uses the web technologies WebGL and HTML5 to enable cross-platform, web-based functionality. Our approach attains interactive rendering framerates; its power and flexibility enables it to serve the needs of the astronomy community. Evaluation on three case studies, as well as feedback from domain experts emphasize the benefits of this visual approach to the observational astronomy field; and its potential benefits to large scale geospatial visualization in general. PMID- 26357361 TI - Shape Deformation via Interior RBF. AB - We present a new framework for real-time shape deformation with local shape preservation and volume control. Given a 3D object, in any form, one would like to manipulate the object using convenient handles, so that the resulting shape is a natural variation of the given object. It is also important that the deformation is controlled, thereby enabling localized changes that do not influence nearby branches. For example, given a horse model, a movement of one of its hooves should not affect the other hooves. Another goal is the minimization of local shape distortion throughout the object. The first ingredient of our method is the use of interior radial basis functions (IRBF), where the functions are radial with respect to interior distances within the object. The second important ingredient is the reduction of local distortions by minimizing the distortion of a set of spheres placed within the object. Our method achieves the goals of convenient shape manipulation and local influence property, and improves the latest state-of-the-art cage-based methods by replacing the cage with the more flexible IRBF centers. The latter enables extra flexibility and fully automated construction, as well as simpler formulation. We also suggest the IRBF interpolation method that can extend any surface mapping to the whole subspace in a shape-aware manner. PMID- 26357362 TI - Structured Mechanical Collage. AB - We present a method to build 3D structured mechanical collages consisting of numerous elements from the database given artist-designed proxy models. The construction is guided by some graphic design principles, namely unity, variety and contrast. Our results are visually more pleasing than previous works as confirmed by a user study. PMID- 26357363 TI - Dynamic Network Visualization withExtended Massive Sequence Views. AB - Networks are present in many fields such as finance, sociology, and transportation. Often these networks are dynamic: they have a structural as well as a temporal aspect. In addition to relations occurring over time, node information is frequently present such as hierarchical structure or time-series data. We present a technique that extends the Massive Sequence View ( msv) for the analysis of temporal and structural aspects of dynamic networks. Using features in the data as well as Gestalt principles in the visualization such as closure, proximity, and similarity, we developed node reordering strategies for the msv to make these features stand out that optionally take the hierarchical node structure into account. This enables users to find temporal properties such as trends, counter trends, periodicity, temporal shifts, and anomalies in the network as well as structural properties such as communities and stars. We introduce the circular msv that further reduces visual clutter. In addition, the (circular) msv is extended to also convey time-series data associated with the nodes. This enables users to analyze complex correlations between edge occurrence and node attribute changes. We show the effectiveness of the reordering methods on both synthetic and a rich real-world dynamic network data set. PMID- 26357364 TI - Joint Contour Nets. AB - Contour Trees and Reeb Graphs are firmly embedded in scientific visualization for analysing univariate (scalar) fields. We generalize this analysis to multivariate fields with a data structure called the Joint Contour Net that quantizes the variation of multiple variables simultaneously. We report the first algorithm for constructing the Joint Contour Net, and demonstrate some of the properties that make it practically useful for visualisation, including accelerating computation by exploiting a relationship with rasterisation in the range of the function. PMID- 26357365 TI - Ovis: A Framework for Visual Analysis of Ocean Forecast Ensembles. AB - We present a novel integrated visualization system that enables interactive visual analysis of ensemble simulations of the sea surface height that is used in ocean forecasting. The position of eddies can be derived directly from the sea surface height and our visualization approach enables their interactive exploration and analysis.The behavior of eddies is important in different application settings of which we present two in this paper. First, we show an application for interactive planning of placement as well as operation of off shore structures using real-world ensemble simulation data of the Gulf of Mexico. Off-shore structures, such as those used for oil exploration, are vulnerable to hazards caused by eddies, and the oil and gas industry relies on ocean forecasts for efficient operations. We enable analysis of the spatial domain, as well as the temporal evolution, for planning the placement and operation of structures.Eddies are also important for marine life. They transport water over large distances and with it also heat and other physical properties as well as biological organisms. In the second application we present the usefulness of our tool, which could be used for planning the paths of autonomous underwater vehicles, so called gliders, for marine scientists to study simulation data of the largely unexplored Red Sea. PMID- 26357366 TI - A Graph-Based Interface for Visual Analytics of 3D Streamlines and Pathlines. AB - Visual exploration of large and complex 3D steady and unsteady flow fields is critically important in many areas of science and engineering. In this paper, we introduce FlowGraph, a novel compound graph representation that organizes field line clusters and spatiotemporal regions hierarchically for occlusion-free and controllable visual exploration. It works with any seeding strategy as long as the domain is well covered and important flow features are captured. By transforming a flow field to a graph representation, we enable observation and exploration of the relationships among field line clusters, spatiotemporal regions and their interconnection in the transformed space. FlowGraph not only provides a visual mapping that abstracts field line clusters and spatiotemporal regions in various levels of detail, but also serves as a navigation tool that guides flow field exploration and understanding. Through brushing and linking in conjunction with the standard field line view, we demonstrate the effectiveness of FlowGraph with several visual exploration and comparison tasks that cannot be well accomplished using the field line view alone. We also perform an empirical expert evaluation to confirm the usefulness of this graph-based technique. PMID- 26357367 TI - Bundled Visualization of DynamicGraph and Trail Data. AB - Depicting change captured by dynamic graphs and temporal paths, or trails, is hard. We present two techniques for simplified visualization of such data sets using edge bundles. The first technique uses an efficient image-based bundling method to create smoothly changing bundles from streaming graphs. The second technique adds edge-correspondence data atop of any static bundling algorithm, and is best suited for graph sequences. We show how these techniques can produce simplified visualizations of streaming and sequence graphs. Next, we show how several temporal attributes can be added atop of our dynamic graphs. We illustrate our techniques with data sets from aircraft monitoring, software engineering, and eye-tracking of static and dynamic scenes. PMID- 26357368 TI - A Survey of Software Frameworks for Cluster-Based Large High-Resolution Displays. AB - Large high-resolution displays (LHRD) enable visualization of extremely large scale data sets with high resolution, large physical size, scalable rendering performance, advanced interaction methods, and collaboration. Despite the advantages, applications for LHRD can be developed only by a select group of researchers and programmers, since its software implementation requires design and development paradigms different from typical desktop environments. It is critical for developers to understand and take advantage of appropriate software tools and methods for developing their LHRD applications. In this paper, we present a survey of the state-of-the-art software frameworks and applications for cluster-based LHRD, highlighting a three-aspect taxonomy. This survey can aid LHRD application and framework developers in choosing more suitable development techniques and software environments for new LHRD applications, and guide LHRD researchers to open needs in LHRD software frameworks. PMID- 26357369 TI - Cone Tracing for Furry Object Rendering. AB - We present a cone-based ray tracing algorithm for high-quality rendering of furry objects with reflection, refraction and defocus effects. By aggregating many sampling rays in a pixel as a single cone, we significantly reduce the high supersampling rate required by the thin geometry of fur fibers. To reduce the cost of intersecting fur fibers with cones, we construct a bounding volume hierarchy for the fiber geometry to find the fibers potentially intersecting with cones, and use a set of connected ribbons to approximate the projections of these fibers on the image plane. The computational cost of compositing and filtering transparent samples within each cone is effectively reduced by approximating away in-cone variations of shading, opacity and occlusion. The result is a highly efficient ray tracing algorithm for furry objects which is able to render images of quality comparable to those generated by alternative methods, while significantly reducing the rendering time. We demonstrate the rendering quality and performance of our algorithm using several examples and a user study. PMID- 26357370 TI - Frame Field Singularity Correction for Automatic Hexahedralization. AB - We present an automatic hexahedralization tool, based on a systematic treatment that removes some of the singularities that would lead to degenerate volumetric parameterization. Such singularities could be abundant in automatically generated frame fields guiding the interior and boundary layouts of the hexahedra in an all hexahedral mesh. We first give the mathematical definitions of the inadmissible singularities prevalent in frame fields, including newly introduced surface singularity types. We then give a practical framework for adjusting singularity graphs by automatically modifying the rotational transition of frames between charts (cells of a tetrahedral mesh for the volume) to resolve the issues detected in the internal and boundary singularity graph. After applying an additional re-smoothing of the frame field with the modified transition conditions, we cut the volume into a topologically trivial domain, with the original topology encoded by the self-intersections of the boundary of the domain, and solve a mixed integer problem on this domain for a global parameterization. Finally, a properly connected hexahedral mesh is constructed from the integer isosurfaces of (u,v,w) in the parameterization. We demonstrate the applicability of the method on complex shapes, and discuss its limitations. PMID- 26357371 TI - Learning Layouts for Single-Page Graphic Designs. AB - This paper presents an approach for automatically creating graphic design layouts using a new energy-based model derived from design principles. The model includes several new algorithms for analyzing graphic designs, including the prediction of perceived importance, alignment detection, and hierarchical segmentation. Given the model, we use optimization to synthesize new layouts for a variety of single page graphic designs. Model parameters are learned with Nonlinear Inverse Optimization (NIO) from a small number of example layouts. To demonstrate our approach, we show results for applications including generating design layouts in various styles, retargeting designs to new sizes, and improving existing designs. We also compare our automatic results with designs created using crowdsourcing and show that our approach performs slightly better than novice designers. PMID- 26357372 TI - Data-Driven Synthetic Modeling of Trees. AB - In this paper, we develop a data-driven technique to model trees from a single laser scan. A multi-layer representation of the tree structure is proposed to guide the modeling process. In this process, a marching cylinder algorithm is first developed to construct visible branches from the laser scan data. Three levels of crown feature points are then extracted from the scan data to synthesize three layers of non-visible branches. Based on the hierarchical particle flow technique, the branch synthesis method has the advantage of producing visually convincing tree models that are consistent with scan data. User intervention is extremely limited. The robustness of this technique has been validated on both conifer and broadleaf trees. PMID- 26357373 TI - Direct Isosurface Ray Casting of NURBS-Based Isogeometric Analysis. AB - In NURBS-based isogeometric analysis, the basis functions of a 3D model's geometric description also form the basis for the solution space of variational formulations of partial differential equations. In order to visualize the results of a NURBS-based isogeometric analysis, we developed a novel GPU-based multi-pass isosurface visualization technique which performs directly on an equivalent rational Bezier representation without the need for discretization or approximation. Our approach utilizes rasterization to generate a list of intervals along the ray that each potentially contain boundary or isosurface intersections. Depth-sorting this list for each ray allows us to proceed in front to-back order and enables early ray termination. We detect multiple intersections of a ray with the higher-order surface of the model using a sampling-based root isolation method. The model's surfaces and the isosurfaces always appear smooth, independent of the zoom level due to our pixel-precise processing scheme. Our adaptive sampling strategy minimizes costs for point evaluations and intersection computations. The implementation shows that the proposed approach interactively visualizes volume meshes containing hundreds of thousands of Bezier elements on current graphics hardware. A comparison to a GPU-based ray casting implementation using spatial data structures indicates that our approach generally performs significantly faster while being more accurate. PMID- 26357374 TI - Drawing Road Networks with Mental Maps. AB - Tourist and destination maps are thematic maps designed to represent specific themes in maps. The road network topologies in these maps are generally more important than the geometric accuracy of roads. A road network warping method is proposed to facilitate map generation and improve theme representation in maps. The basic idea is deforming a road network to meet a user-specified mental map while an optimization process is performed to propagate distortions originating from road network warping. To generate a map, the proposed method includes algorithms for estimating road significance and for deforming a road network according to various geometric and aesthetic constraints. The proposed method can produce an iconic mark of a theme from a road network and meet a user-specified mental map. Therefore, the resulting map can serve as a tourist or destination map that not only provides visual aids for route planning and navigation tasks, but also visually emphasizes the presentation of a theme in a map for the purpose of advertising. In the experiments, the demonstrations of map generations show that our method enables map generation systems to generate deformed tourist and destination maps efficiently. PMID- 26357375 TI - Efficient Structure-Aware Image Smoothingby Local Extrema on Space-Filling Curve. AB - This paper presents a novel image smoothing approach using a space-filling curve as the reduced domain to perform separation of edges and details. This structure aware smoothing effect is achieved by modulating local extrema after empirical mode decomposition; it is highly effective and efficient since it is implemented on a one-dimensional curve instead of a two-dimensional image grid. To overcome edge staircase-like artifacts caused by a neighborhood deficiency in domain reduction, we next use a joint contrast-based filter to consolidate edge structures in image smoothing. The adoption of dimensional reduction makes our smoothing approach distinct for two reasons. First, overall structure-awareness is improved as more extrema are exploited to locate the salient edges and details. Second, envelope computation for local extrema is made much fast by using explicit interpolants on the curve. Moreover, our approach is simple and very easy to implement in practice. Experimental results demonstrate the merit of our approach, which outperforms previous state-of-the-art methods, for a variety of image processing tasks. PMID- 26357376 TI - Implicit Multibody Penalty-BasedDistributed Contact. AB - The penalty method is a simple and popular approach to resolving contact in computer graphics and robotics. Penalty-based contact, however, suffers from stability problems due to the highly variable and unpredictable net stiffness, and this is particularly pronounced in simulations with time-varying distributed geometrically complex contact. We employ semi-implicit integration, exact analytical contact gradients, symbolic Gaussian elimination and a SVD solver to simulate stable penalty-based frictional contact with large, time-varying contact areas, involving many rigid objects and articulated rigid objects in complex conforming contact and self-contact. We also derive implicit proportional derivative control forces for real-time control of articulated structures with loops. We present challenging contact scenarios such as screwing a hexbolt into a hole, bowls stacked in perfectly conforming configurations, and manipulating many objects using actively controlled articulated mechanisms in real time. PMID- 26357377 TI - Large-Scale Point-Cloud Visualization through Localized Textured Surface Reconstruction. AB - In this paper, we introduce a novel scene representation for the visualization of large-scale point clouds accompanied by a set of high-resolution photographs. Many real-world applications deal with very densely sampled point-cloud data, which are augmented with photographs that often reveal lighting variations and inaccuracies in registration. Consequently, the high-quality representation of the captured data, i.e., both point clouds and photographs together, is a challenging and time-consuming task. We propose a two-phase approach, in which the first (preprocessing) phase generates multiple overlapping surface patches and handles the problem of seamless texture generation locally for each patch. The second phase stitches these patches at render-time to produce a high-quality visualization of the data. As a result of the proposed localization of the global texturing problem, our algorithm is more than an order of magnitude faster than equivalent mesh-based texturing techniques. Furthermore, since our preprocessing phase requires only a minor fraction of the whole data set at once, we provide maximum flexibility when dealing with growing data sets. PMID- 26357378 TI - Making Graphical Information Visible in Real Shadows on Interactive Tabletops. AB - We introduce a shadow-based interface for interactive tabletops. The proposed interface allows a user to browse graphical information by casting the shadow of his/her body, such as a hand, on a tabletop surface. Central to our technique is a new optical design that utilizes polarization in addition to the additive nature of light so that the desired graphical information is displayed only in a shadow area on a tabletop surface. In other words, our technique conceals the graphical information on surfaces other than the shadow area, such as the surface of the occluder and non-shadow areas on the tabletop surface. We combine the proposed shadow-based interface with a multi-touch detection technique to realize a novel interaction technique for interactive tabletops. We implemented a prototype system and conducted proof-of-concept experiments along with a quantitative evaluation to assess the feasibility of the proposed optical design. Finally, we showed implemented application systems of the proposed shadow-based interface. PMID- 26357379 TI - Object Movements Synopsis via Part Assembling and Stitching. AB - Video synopsis aims at removing video's less important information, while preserving its key content for fast browsing, retrieving, or efficient storing. Previous video synopsis methods, including frame-based and object-based approaches that remove valueless whole frames or combine objects from time shots, cannot handle videos with redundancies existing in the movements of video object. In this paper, we present a novel part-based object movements synopsis method, which can effectively compress the redundant information of a moving video object and represent the synopsized object seamlessly. Our method works by part-based assembling and stitching. The object movement sequence is first divided into several part movement sequences. Then, we optimally assemble moving parts from different part sequences together to produce an initial synopsis result. The optimal assembling is formulated as a part movement assignment problem on a Markov Random Field (MRF), which guarantees the most important moving parts are selected while preserving both the spatial compatibility between assembled parts and the chronological order of parts. Finally, we present a non-linear spatiotemporal optimization formulation to stitch the assembled parts seamlessly, and achieve the final compact video object synopsis. The experiments on a variety of input video objects have demonstrated the effectiveness of the presented synopsis method. PMID- 26357380 TI - Second-Order Feed-Forward Renderingfor Specular and Glossy Reflections. AB - The feed-forward pipeline based on projection followed by rasterization handles the rays that leave the eye efficiently: these first-order rays are modeled with a simple camera that projects geometry to screen. Second-order rays however, as, for example, those resulting from specular reflections, are challenging for the feed-forward approach. We propose an extension of the feed-forward pipeline to handle second-order rays resulting from specular and glossy reflections. The coherence of second-order rays is leveraged through clustering, the geometry reflected by a cluster is approximated with a depth image, and the color samples captured by the second-order rays of a cluster are computed by intersection with the depth image. We achieve quality specular and glossy reflections at interactive rates in fully dynamic scenes. PMID- 26357381 TI - Volume Rendering of Curvilinear-Grid Data Using Low-Dimensional Deformation Textures. AB - In this paper, we present a high quality and interactive method for volume rendering curvilinear-grid data sets. This method is based on a two-stage parallel transformation of the sample position into intermediate computational space then into texture space through the use of multiple 1 and 2D deformation textures using hardware acceleration. In this manner, it is possible to render many curvilinear-grid volume data sets at high quality and with a low memory footprint, while taking advantage of modern graphic hardware's tri-linear filtering for the data itself. We also extend our method to handle volume shading. Additionally, we present a comprehensive study and comparisons with previous works, we show improvements both in quality and performance using our technique on multiple curvilinear data sets. PMID- 26357382 TI - Diverse Motions and Character Shapes for Simulated Skills. AB - We present an optimization framework that produces a diverse range of motions for physics-based characters for tasks such as jumps, flips, and walks. This stands in contrast to the more common use of optimization to produce a single optimal motion. The solutions can be optimized to achieve motion diversity or diversity in the proportions of the simulated characters. As input, the method takes a character model, a parameterized controller for a successful motion instance, a set of constraints that should be preserved, and a pairwise distance metric. An offline optimization then produces a highly diverse set of motion styles or, alternatively, motions that are adapted to a diverse range of character shapes. We demonstrate results for a variety of 2D and 3D physics-based motions, showing that the approach can generate compelling new variations of simulated skills. PMID- 26357383 TI - Control of Rotational Dynamics for Ground and Aerial Behavior. AB - This paper proposes a physics-based framework to control rolling, flipping and other behaviors with significant rotational components. The proposed technique is a general approach for guiding coordinated action that can be layered over existing control architectures through the purposeful regulation of specific whole-body features. Namely, we apply control for rotation through the specification and execution of specific desired 'rotation indices' for whole-body orientation, angular velocity and angular momentum control and highlight the use of the angular excursion as a means for whole-body rotation control. We account for the stylistic components of behaviors through reference posture control. The novelty of the described work includes control over behaviors with considerable rotational components, both on the ground and in the air as well as a number of characteristics useful for general control, such as flight planning with inertia modeling, compliant posture tracking, and contact control planning. PMID- 26357384 TI - Geodesic Binding for Degenerate Character Geometry Using Sparse Voxelization. AB - We propose a fully automatic method for specifying influence weights for closed form skinning methods, such as linear blend or dual quaternion skinning. Our method is designed to work with production meshes that may contain non-manifold geometry, be non-watertight, have intersecting triangles, or be comprised of multiple connected components. Starting from a character rest pose mesh and skeleton hierarchy, we first voxelize the input geometry. The resulting sparse voxelization is then used to calculate binding weights, based on the geodesic distance between each voxel lying on a skeleton "bone" and all non-exterior voxels. This yields smooth weights at interactive rates, without time-constants, iteration parameters, or costly optimization at bind or pose time. By decoupling weight assignment from distance computation we make it possible to modify weights interactively, at pose time, without additional pre-processing or computation. This allows artists to assess impact of weight selection in the context in which they are used. PMID- 26357385 TI - Data-Driven Simulation of Detailed Surface Deformations for Surgery Training Simulators. AB - Data-driven methods have received increasing attention in recent years in order to meet real-time requirements in computationally intensive tasks. In our current work we examine the application of such approaches in soft-tissue simulation. The core idea is to split deformations into a coarse approximation and a differential part that contains the details. We employ the data-driven stamping approach to enrich a fast simulation surface with details that have been extracted from a set of example deformations obtained in offline computations. In this paper we detail our technique, and suggest further extensions over our previous work. First, we propose an improved method for correlating the current coarse approximation to the examples in the database. The new correlation metric combines Euclidean distances with cosine similarity. It allows for better example discrimination, resulting in a well-conditioned linear system. This also enables us to use a non negative least squares solver that leads to a better regression and guarantees positive stamp blending weights. Second, we suggest a frequency-space stamp compression scheme that saves memory and, in most instances, is faster, since many operations can be done in the compressed space. Third, cutting is included by employing a physically-inspired influence map that allows for proper handling of material discontinuities that were not present in the original examples. We thoroughly evaluate our method and demonstrate its practical application in a surgical simulator prototype. PMID- 26357386 TI - Exploring Flow Fields Using Space-Filling Analysis of Streamlines. AB - Large scale scientific simulations frequently use streamline based techniques to visualize flow fields. As the shape of a streamline is often related to some underlying property of the field, it is important to identify streamlines (or their parts) with unique geometric features. In this paper, we introduce a metric, called the box counting ratio, which measures the geometric complexity of streamlines by measuring their space-filling capacity at different scales. We propose a novel interactive visualization framework which utilizes this metric to extract, organize and visualize features of varying density and complexity hidden in large numbers of streamlines. The proposed framework extracts complex regions of varying density from the streamlines, and organizes and presents them on an interactive 2D information space, allowing user selection and visualization of streamlines. We also extend this framework to support exploration using an ensemble of measures including box counting ratio. Our framework allows the user to easily visualize and interact with features otherwise hidden in large vector field data. We strengthen our claims with case studies using combustion and climate simulation data sets. PMID- 26357387 TI - Large-Scale Liquid Simulation on Adaptive Hexahedral Grids. AB - Regular grids are attractive for numerical fluid simulations because they give rise to efficient computational kernels. However, for simulating high resolution effects in complicated domains they are only of limited suitability due to memory constraints. In this paper we present a method for liquid simulation on an adaptive octree grid using a hexahedral finite element discretization, which reduces memory requirements by coarsening the elements in the interior of the liquid body. To impose free surface boundary conditions with second order accuracy, we incorporate a particular class of Nitsche methods enforcing the Dirichlet boundary conditions for the pressure in a variational sense. We then show how to construct a multigrid hierarchy from the adaptive octree grid, so that a time efficient geometric multigrid solver can be used. To improve solver convergence, we propose a special treatment of liquid boundaries via composite finite elements at coarser scales. We demonstrate the effectiveness of our method for liquid simulations that would require hundreds of millions of simulation elements in a non-adaptive regime. PMID- 26357388 TI - Low-Resolution Remeshing Using the Localized Restricted Voronoi Diagram. AB - A big problem in triangular remeshing is to generate meshes when the triangle size approaches the feature size in the mesh. The main obstacle for Centroidal Voronoi Tessellation (CVT)-based remeshing is to compute a suitable Voronoi diagram. In this paper, we introduce the localized restricted Voronoi diagram (LRVD) on mesh surfaces. The LRVD is an extension of the restricted Voronoi diagram (RVD), but it addresses the problem that the RVD can contain Voronoi regions that consist of multiple disjoint surface patches. Our definition ensures that each Voronoi cell in the LRVD is a single connected region. We show that the LRVD is a useful extension to improve several existing mesh-processing techniques, most importantly surface remeshing with a low number of vertices. While the LRVD and RVD are identical in most simple configurations, the LRVD is essential when sampling a mesh with a small number of points and for sampling surface areas that are in close proximity to other surface areas, e.g., nearby sheets. To compute the LRVD, we combine local discrete clustering with a global exact computation. PMID- 26357389 TI - On View Consistency in Multi-Server Distributed Virtual Environments. AB - A distributed virtual environment (DVE) is a shared virtual environment (VE) that allows remote users to interact with each other through networks. DVEs are becoming very popular due to some prominent applications, such as online games and virtual worlds. To support a large number of users, a multi-server DVE architecture may be adopted, with each server managing a subset of users. However, there are two critical problems with this architecture: view inconsistency caused by delays and server overloading caused by uneven distribution of users. While the first problem affects users' perception of the VE and causes user disputes, the second problem affects the system response time. In this paper, we first show that the view inconsistency problem and the load balancing problem are conflicting objectives. We then propose an efficient joint optimization framework to address both problems. Our results show that the proposed method can improve the view inconsistency problem significantly, which is important to the interactivity of DVE applications. PMID- 26357390 TI - Overestimation and Underestimation Biases in Photon Mapping with Non-Constant Kernels. AB - This paper presents an analysis of the overestimation bias in common used filtering kernels in the context of photon mapping density estimation. We use the joint distribution of order statistics to calculate the expected value of the estimators of irradiance, and show that the estimator provided by the cone filter is not consistent unless the slope is one (yielding the triangular kernel), and that the Epanechnikov and Silverman kernels are consistent. The Gaussian filter has two different estimation biases: the original normalization constant alpha underestimates radiance by 46.9 percent, and the use of the kth nearest photon reduces this underestimation slightly. We also show that a new normalization constant for the Gaussian filter together with discarding the contribution of the kth nearest photon in the Gaussian and cone filter estimators produces new, consistent estimators. The specialized differential filter also benefits from the new estimate. PMID- 26357391 TI - Towards Photo Watercolorization with Artistic Verisimilitude. AB - We present a novel artistic-verisimilitude driven system for watercolor rendering of images and photos. Our system achieves realistic simulation of a set of important characteristics of watercolor paintings that have not been well implemented before. Specifically, we designed several image filters to achieve: 1) watercolor-specified color transferring; 2) saliency-based level-of-detail drawing; 3) hand tremor effect due to human neural noise; and 4) an artistically controlled wet-in-wet effect in the border regions of different wet pigments. A user study indicates that our method can produce watercolor results of artistic verisimilitude better than previous filter-based or physical-based methods. Furthermore, our algorithm is efficient and can easily be parallelized, making it suitable for interactive image watercolorization. PMID- 26357392 TI - Zometool Rationalization of Freeform Surfaces. AB - An ever broader availability of freeform designs together with an increasing demand for product customization has lead to a rising interest in efficient physical realization of such designs, the trend toward personal fabrication. Not only large-scale architectural applications are (becoming increasingly) popular but also different consumer-level rapid-prototyping applications, including toy and 3D puzzle creation. In this work we present a method for do-it-yourself reproduction of freeform designs without the typical limitation of state-of-the art approaches requiring manufacturing custom parts using semi-professional laser cutters or 3D printers. Our idea is based on a popular mathematical modeling system (Zometool) commonly used for modeling higher dimensional polyhedra and symmetric structures such as molecules and crystal lattices. The proposed method extends the scope of Zometool modeling to freeform, disk-topology surfaces. While being an efficient construction system on the one hand (consisting only of a single node type and nine different edge types), this inherent discreteness of the Zometool system, on the other hand gives rise to a hard approximation problem. We base our method on a marching front approach, where elements are not added in a greedy sense, but rather whole regions on the front are filled optimally, using a set of problem specific heuristics to keep complexity under control. PMID- 26357393 TI - Automatic Classification of the Vestibulo-Ocular Reflex Nystagmus: Integration of Data Clustering and System Identification. AB - The vestibulo-ocular reflex (VOR) plays an important role in our daily activities by enabling us to fixate on objects during head movements. Modeling and identification of the VOR improves our insight into the system behavior and improves diagnosis of various disorders. However, the switching nature of eye movements (nystagmus), including the VOR, makes dynamic analysis challenging. The first step in such analysis is to segment data into its subsystem responses (here slow and fast segment intervals). Misclassification of segments results in biased analysis of the system of interest. Here, we develop a novel three-step algorithm to classify the VOR data into slow and fast intervals automatically. The proposed algorithm is initialized using a K-means clustering method. The initial classification is then refined using system identification approaches and prediction error statistics. The performance of the algorithm is evaluated on simulated and experimental data. It is shown that the new algorithm performance is much improved over the previous methods, in terms of higher specificity. PMID- 26357394 TI - Objective Assessment of Upper-Limb Mobility for Poststroke Rehabilitation. AB - The assessment of the limb mobility of stroke patients is an essential part of poststroke rehabilitation. Conventionally, the assessment is manually performed by clinicians using chart-based ordinal scales, which can be subjective and inefficient. By introducing quantitative evaluation measures, the sensitivity and efficiency of the assessment process can be significantly improved. In this paper, a novel single-index-based assessment approach for quantitative upper-limb mobility evaluation has been proposed for poststroke rehabilitation. Instead of the traditional human-observation-based measures, the proposed assessment system utilizes the kinematic information automatically collected during a regular rehabilitation training exercise using a wearable inertial measurement unit. By calculating a single index, the system can efficiently generate objective and consistent quantitative results that can reflect the stroke patient's upper-limb mobility. In order to verify and validate the proposed assessment system, experiments have been conducted using 145 motion samples collected from 21 stroke patients (12 males, nine females, mean age 58.7+/-19.3) and eight healthy participants. The results have suggested that the proposed assessment index can not only differentiate the levels of limb function impairment clearly (p < 0.001, two-tailed Welch's t-test), but also strongly correlate with the Brunnstrom stages of recovery (r = 0.86, p < 0.001). The assessment index is also proven to have great potential in automatic Brunnstrom stage classification application with an 82.1% classification accuracy, while using a K-nearest-neighbor classifier. PMID- 26357396 TI - Nested Graph Cut for Automatic Segmentation of High-Frequency Ultrasound Images of the Mouse Embryo. AB - We propose a fully automatic segmentation method called nested graph cut to segment images (2D or 3D) that contain multiple objects with a nested structure. Compared to other graph-cut-based methods developed for multiple regions, our method can work well for nested objects without requiring manual selection of initial seeds, even if different objects have similar intensity distributions and some object boundaries are missing. Promising results were obtained for separating the brain ventricles, the head, and the uterus region in the mouse embryo head images obtained using high-frequency ultrasound imaging. The proposed method achieved mean Dice similarity coefficients of 0.87 +/-0.04 and 0.89 +/ 0.06 for segmenting BVs and the head, respectively, compared to manual segmentation results by experts on 40 3D images over five gestation stages. PMID- 26357395 TI - Design and In Vivo Test of a Batteryless and Fully Wireless Implantable Asynchronous Pacing System. AB - : Goal: The aim of this study is to develop a novel fully wireless and batteryless technology for cardiac pacing. METHODS: This technology uses radio frequency (RF) energy to power the implanted electrode in the heart. An implantable electrode antenna was designed for 1.2 GHz; then, it was tested in vitro and, subsequently, integrated with the rectifier and pacing circuit to make a complete electrode. The prototype implanted electrode was tested in vivo in an ovine subject, implanting it on the epicardial surface of the left ventricle. The RF energy, however, was transmitted to the implanted electrode using a horn antenna positioned 25 cm above the thorax of the sheep. RESULTS: It was demonstrated that a small implanted electrode can capture and harvest enough safe recommended RF energy to achieve pacing. Electrocardiogram signals were recorded during the experiments, which demonstrated asynchronous pacing achieved at three different rates. CONCLUSION: These results show that the proposed method has a great potential to be used for stimulating the heart and provides pacing, without requiring any leads or batteries. It hence has the advantage of potentially lasting indefinitely and may never require replacement during the life of the patient. SIGNIFICANCE: The proposed method brings forward transformational possibilities in wireless cardiac pacing, and also in powering up the implantable devices. PMID- 26357397 TI - Extremal Regions Detection Guided by Maxima of Gradient Magnitude. AB - A problem of computer vision applications is to detect regions of interest under different imaging conditions. The state-of-the-art maximally stable extremal regions (MSERs) detects affine covariant regions by applying all possible thresholds on the input image, and through three main steps including: (1) making a component tree of extremal regions' evolution; (2) obtaining region stability criterion; and (3) cleaning up. The MSER performs very well, but, it does not consider any information about the boundaries of the regions, which are important for detecting repeatable extremal regions. We have shown in this paper that employing prior information about boundaries of regions results in a novel region detector algorithm that not only outperforms MSER, but avoids the MSER's rather complicated steps of enumeration and the cleaning up. To employ the information about the region boundaries, we introduce maxima of gradient magnitudes (MGMs) which are shown to be points that are mostly around the boundaries of the regions. Having found the MGMs, the method obtains a global criterion for each level of the input image which is used to find extremum levels (ELs). The found ELs are then used to detect extremal regions. The proposed algorithm which is called extremal regions of extremum levels (EREL) has been tested on the public benchmark data set of Mikolajczyk. The obtained experimental results show that the inclusion of region boundaries through MGMs, results in a detector that detects regions with high repeatability scores and is more robust against noise compared with MSER. PMID- 26357398 TI - SensePath: Understanding the Sensemaking Process Through Analytic Provenance. AB - Sensemaking is described as the process of comprehension, finding meaning and gaining insight from information, producing new knowledge and informing further action. Understanding the sensemaking process allows building effective visual analytics tools to make sense of large and complex datasets. Currently, it is often a manual and time-consuming undertaking to comprehend this: researchers collect observation data, transcribe screen capture videos and think-aloud recordings, identify recurring patterns, and eventually abstract the sensemaking process into a general model. In this paper, we propose a general approach to facilitate such a qualitative analysis process, and introduce a prototype, SensePath, to demonstrate the application of this approach with a focus on browser-based online sensemaking. The approach is based on a study of a number of qualitative research sessions including observations of users performing sensemaking tasks and post hoc analyses to uncover their sensemaking processes. Based on the study results and a follow-up participatory design session with HCI researchers, we decided to focus on the transcription and coding stages of thematic analysis. SensePath automatically captures user's sensemaking actions, i.e., analytic provenance, and provides multi-linked views to support their further analysis. A number of other requirements elicited from the design session are also implemented in SensePath, such as easy integration with existing qualitative analysis workflow and non-intrusive for participants. The tool was used by an experienced HCI researcher to analyze two sensemaking sessions. The researcher found the tool intuitive and considerably reduced analysis time, allowing better understanding of the sensemaking process. PMID- 26357399 TI - InterAxis: Steering Scatterplot Axes via Observation-Level Interaction. AB - Scatterplots are effective visualization techniques for multidimensional data that use two (or three) axes to visualize data items as a point at its corresponding x and y Cartesian coordinates. Typically, each axis is bound to a single data attribute. Interactive exploration occurs by changing the data attributes bound to each of these axes. In the case of using scatterplots to visualize the outputs of dimension reduction techniques, the x and y axes are combinations of the true, high-dimensional data. For these spatializations, the axes present usability challenges in terms of interpretability and interactivity. That is, understanding the axes and interacting with them to make adjustments can be challenging. In this paper, we present InterAxis, a visual analytics technique to properly interpret, define, and change an axis in a user-driven manner. Users are given the ability to define and modify axes by dragging data items to either side of the x or y axes. from which the system computes a linear combination of data attributes and binds it to the axis. Further, users can directly tune the positive and negative contribution to these complex axes by using the visualization of data attributes that correspond to each axis. We describe the details of our technique and demonstrate the intended usage through two scenarios. PMID- 26357400 TI - Enhancing Light Fields through Ray-Space Stitching. AB - Light fields (LFs) have been shown to enable photorealistic visualization of complex scenes. In practice, however, an LF tends to have a relatively small angular range or spatial resolution, which limits the scope of virtual navigation. In this paper, we show how seamless virtual navigation can be enhanced by stitching multiple LFs. Our technique consists of two key components: LF registration and LF stitching. To register LFs, we use what we call the ray space motion matrix (RSMM) to establish pairwise ray-ray correspondences. Using Plucker coordinates, we show that the RSMM is a 5 *6 matrix, which reduces to a 5 *5 matrix under pure translation and/or in-plane rotation. The final LF stitching is done using multi-resolution, high-dimensional graph-cut in order to account for possible scene motion, imperfect RSMM estimation, and/or undersampling. We show how our technique allows us to create LFs with various enhanced features: extended horizontal and/or vertical field-of-view, larger synthetic aperture and defocus blur, and larger parallax. PMID- 26357401 TI - Analysis of Gait Rhythm Fluctuations for Neurodegenerative Diseases by Phase Synchronization and Conditional Entropy. AB - Previous studies have revealed that gait rhythm fluctuations convey important information, which is useful for understanding certain types of neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS), Huntington's disease (HD) and Parkinson's disease (PD). However, previous investigations only focused on the locomotor patterns of each individual foot rather than the relations between both feet. Therefore, in our study, phase synchronization (the index rho) and conditional entropy (Hc) were applied to the five types of time series pairs of gait rhythms (stride time, swing time, stance time, % swing time and % stance time). The results revealed that compared with the patients with ALS, HD and PD, gait rhythms of normal subjects have the strongest phase synchronization property and minimum conditional entropy value. In addition, the indices rho and Hc cannot only significantly differentiate among the four groups of subjects (ALS, HD, PD and control) but also have the ability to discriminate between any two of these subject groups. Finally, three representative classifiers were utilized in order to evaluate the possible capabilities of the indices rho and Hc to distinguish the patients with neurodegenerative diseases from the healthy subjects, and achieved maximum area under the curve (AUC) values of 0.959, 0.928 and 0.824 for HD, PD and ALS detection, respectively. In summary, our study provides insight into the relational analysis between gait rhythms measured from both feet, and suggests that it should be considered seriously in the future studies investigating the impact of neurodegenerative disease and potential therapeutic intervention. PMID- 26357402 TI - Gait Analysis From a Single Ear-Worn Sensor: Reliability and Clinical Evaluation for Orthopaedic Patients. AB - Objective assessment of detailed gait patterns after orthopaedic surgery is important for post-surgical follow-up and rehabilitation. The purpose of this paper is to assess the use of a single ear-worn sensor for clinical gait analysis. A reliability measure is devised for indicating the confidence level of the estimated gait events, allowing it to be used in free-walking environments and for facilitating clinical assessment of orthopaedic patients after surgery. Patient groups prior to or following anterior cruciate ligament (ACL) reconstruction and knee replacement were recruited to assess the proposed method. The ability of the sensor for detailed longitudinal analysis is demonstrated with a group of patients after lower limb reconstruction by considering parameters such as temporal and force-related gait asymmetry derived from gait events. The results suggest that the ear-worn sensor can be used for objective gait assessments of orthopaedic patients without the requirement and expense of an elaborate laboratory setup for gait analysis. It significantly simplifies the monitoring protocol and opens the possibilities for home-based remote patient assessment. PMID- 26357403 TI - A Dimensionally Reduced Clustering Methodology for Heterogeneous Occupational Medicine Data Mining. AB - Clustering is a set of techniques of the statistical learning aimed at finding structures of heterogeneous partitions grouping homogenous data called clusters. There are several fields in which clustering was successfully applied, such as medicine, biology, finance, economics, etc. In this paper, we introduce the notion of clustering in multifactorial data analysis problems. A case study is conducted for an occupational medicine problem with the purpose of analyzing patterns in a population of 813 individuals. To reduce the data set dimensionality, we base our approach on the Principal Component Analysis (PCA), which is the statistical tool most commonly used in factorial analysis. However, the problems in nature, especially in medicine, are often based on heterogeneous type qualitative-quantitative measurements, whereas PCA only processes quantitative ones. Besides, qualitative data are originally unobservable quantitative responses that are usually binary-coded. Hence, we propose a new set of strategies allowing to simultaneously handle quantitative and qualitative data. The principle of this approach is to perform a projection of the qualitative variables on the subspaces spanned by quantitative ones. Subsequently, an optimal model is allocated to the resulting PCA-regressed subspaces. PMID- 26357404 TI - Extracting Biomedical Event with Dual Decomposition Integrating Word Embeddings. AB - Extracting biomedical event from literatures has attracted much attention recently. By now, most of the state-of-the-art systems have been based on pipelines which suffer from cascading errors, and the words encoded by one-hot are unable to represent the semantic information. Joint inference with dual decomposition and novel word embeddings are adopted to address the two problems, respectively, in this work. Word embeddings are learnt from large scale unlabeled texts and integrated as an unsupervised feature into other rich features based on dependency parse graphs to detect triggers and arguments. The proposed system consists of four components: trigger detector, argument detector, jointly inference with dual decomposition, and rule-based semantic post-processing, and outperforms the state-of-the-art systems. On the development set of BioNLP'09, the F-score is 59.77 percent on the primary task, which is 0.96 percent higher than the best system. On the test set of BioNLP'11, the F-score is 56.09 and 0.89 percent higher than the best published result that do not adopt additional techniques. On the test set of BioNLP'13, the F-score reaches 53.19 percent which is 2.22 percent higher than the best result. PMID- 26357405 TI - CMOS Image Sensor and System for Imaging Hemodynamic Changes in Response to Deep Brain Stimulation. AB - Deep brain stimulation (DBS) is a therapeutic intervention used for a variety of neurological and psychiatric disorders, but its mechanism of action is not well understood. It is known that DBS modulates neural activity which changes metabolic demands and thus the cerebral circulation state. However, it is unclear whether there are correlations between electrophysiological, hemodynamic and behavioral changes and whether they have any implications for clinical benefits. In order to investigate these questions, we present a miniaturized system for spectroscopic imaging of brain hemodynamics. The system consists of a 144 *144, [Formula: see text] pixel pitch, high-sensitivity, analog-output CMOS imager fabricated in a standard 0.35 MUm CMOS process, along with a miniaturized imaging system comprising illumination, focusing, analog-to-digital conversion and MUSD card based data storage. This enables stand alone operation without a computer, nor electrical or fiberoptic tethers. To achieve high sensitivity, the pixel uses a capacitive transimpedance amplifier (CTIA). The nMOS transistors are in the pixel while pMOS transistors are column-parallel, resulting in a fill factor (FF) of 26%. Running at 60 fps and exposed to 470 nm light, the CMOS imager has a minimum detectable intensity of 2.3 nW/cm(2) , a maximum signal-to-noise ratio (SNR) of 49 dB at 2.45 MUW/cm(2) leading to a dynamic range (DR) of 61 dB while consuming 167 MUA from a 3.3 V supply. In anesthetized rats, the system was able to detect temporal, spatial and spectral hemodynamic changes in response to DBS. PMID- 26357406 TI - Designing Conservation Relations in Layered Synthetic Biomolecular Networks. AB - In Synthetic Biology, biomolecular networks are designed and constructed to perform specified tasks. Design strategies for these networks tend to center on tuning the parameters of mathematical models to achieve a specified behavior, and implementing these parameters experimentally. This design strategy often assumes a fixed network structure that defines the possible behaviors, which may be too restrictive for our purposes. This paper investigates the extent to which the state space of a synthetic network can also be designed and shaped by parametric tuning. We exploit timescale separation to implement new, nonlinear, tunable conservation relations that hold for all times beyond a fast transient. We demonstrate an application of this design strategy by flexibly constraining the possible behaviors of a gene regulatory network through the design of fast protein interactions. PMID- 26357407 TI - The Effect of Trial-by-Trial Adaptation on Conflicts in Haptic Shared Control for Free-Air Teleoperation Tasks. AB - Haptic shared control can improve execution of teleoperation and driving tasks. However, shared control designs may suffer from conflicts between individual human operators and constant haptic assistance when their desired trajectories differ, leading to momentarily increased forces, discomfort, or even deteriorated performance. This study investigates ways to reduce conflicts between individual human operators and a haptic shared controller by modifying supported trajectories. Subjects (n=12) performed a repetitive movement task in an abstract environment with varying spatio-temporal constraints, both during manual control and while supported by haptic shared control. Four types of haptic shared control were compared, combining two design properties: the initial supported trajectory (either the centerline of the environment or an individualized trajectory based on manual control trials), and trial-by-trial adaptation of guidance towards previously performed trajectories (either present or absent). Trial-by-trial adaptation of guidance reduced conflicts compared to non-adaptive guidance, whether the initial trajectory was individualized or not. Without trial-by-trial adaptation, individualized trajectories also reduced conflicts, but not completely: when guided, operators adapt their preferred trajectories. In conclusion, trial-by-trial adaptation is the most promising approach to mitigate conflicts during repetitive motion tasks. PMID- 26357408 TI - Neurodynamics-Based Robust Pole Assignment for High-Order Descriptor Systems. AB - In this paper, a neurodynamic optimization approach is proposed for synthesizing high-order descriptor linear systems with state feedback control via robust pole assignment. With a new robustness measure serving as the objective function, the robust eigenstructure assignment problem is formulated as a pseudoconvex optimization problem. A neurodynamic optimization approach is applied and shown to be capable of maximizing the robust stability margin for high-order singular systems with guaranteed optimality and exact pole assignment. Two numerical examples and vehicle vibration control application are discussed to substantiate the efficacy of the proposed approach. PMID- 26357410 TI - Similarity Constraints-Based Structured Output Regression Machine: An Approach to Image Super-Resolution. AB - For regression-based single-image super-resolution (SR) problem, the key is to establish a mapping relation between high-resolution (HR) and low-resolution (LR) image patches for obtaining a visually pleasing quality image. Most existing approaches typically solve it by dividing the model into several single-output regression problems, which obviously ignores the circumstance that a pixel within an HR patch affects other spatially adjacent pixels during the training process, and thus tends to generate serious ringing artifacts in resultant HR image as well as increase computational burden. To alleviate these problems, we propose to use structured output regression machine (SORM) to simultaneously model the inherent spatial relations between the HR and LR patches, which is propitious to preserve sharp edges. In addition, to further improve the quality of reconstructed HR images, a nonlocal (NL) self-similarity prior in natural images is introduced to formulate as a regularization term to further enhance the SORM based SR results. To offer a computation-effective SORM method, we use a relative small nonsupport vector samples to establish the accurate regression model and an accelerating algorithm for NL self-similarity calculation. Extensive SR experiments on various images indicate that the proposed method can achieve more promising performance than the other state-of-the-art SR methods in terms of both visual quality and computational cost. PMID- 26357409 TI - Multiple Representations-Based Face Sketch-Photo Synthesis. AB - Face sketch-photo synthesis plays an important role in law enforcement and digital entertainment. Most of the existing methods only use pixel intensities as the feature. Since face images can be described using features from multiple aspects, this paper presents a novel multiple representations-based face sketch photo-synthesis method that adaptively combines multiple representations to represent an image patch. In particular, it combines multiple features from face images processed using multiple filters and deploys Markov networks to exploit the interacting relationships between the neighboring image patches. The proposed framework could be solved using an alternating optimization strategy and it normally converges in only five outer iterations in the experiments. Our experimental results on the Chinese University of Hong Kong (CUHK) face sketch database, celebrity photos, CUHK Face Sketch FERET Database, IIIT-D Viewed Sketch Database, and forensic sketches demonstrate the effectiveness of our method for face sketch-photo synthesis. In addition, cross-database and database-dependent style-synthesis evaluations demonstrate the generalizability of this novel method and suggest promising solutions for face identification in forensic science. PMID- 26357411 TI - Adaptive Actor-Critic Design-Based Integral Sliding-Mode Control for Partially Unknown Nonlinear Systems With Input Disturbances. AB - This paper is concerned with the problem of integral sliding-mode control for a class of nonlinear systems with input disturbances and unknown nonlinear terms through the adaptive actor-critic (AC) control method. The main objective is to design a sliding-mode control methodology based on the adaptive dynamic programming (ADP) method, so that the closed-loop system with time-varying disturbances is stable and the nearly optimal performance of the sliding-mode dynamics can be guaranteed. In the first step, a neural network (NN)-based observer and a disturbance observer are designed to approximate the unknown nonlinear terms and estimate the input disturbances, respectively. Based on the NN approximations and disturbance estimations, the discontinuous part of the sliding-mode control is constructed to eliminate the effect of the disturbances and attain the expected equivalent sliding-mode dynamics. Then, the ADP method with AC structure is presented to learn the optimal control for the sliding-mode dynamics online. Reconstructed tuning laws are developed to guarantee the stability of the sliding-mode dynamics and the convergence of the weights of critic and actor NNs. Finally, the simulation results are presented to illustrate the effectiveness of the proposed method. PMID- 26357412 TI - Convergence Rate for Discrete-Time Multiagent Systems With Time-Varying Delays and General Coupling Coefficients. AB - Multiagent systems (MASs) are ubiquitous in our real world. There is an increasing attention focusing on the consensus (or synchronization) problem of MASs over the past decade. Although there are numerous results reported on the convergence of a discrete-time MAS based on the infinite products of matrices, few results are on the convergence rate. Because of the switching topology, the traditional eigenvalue analysis and the Lyapunov function methods are both invalid for the convergence rate analysis of an MAS with a switching topology. Therefore, the estimation of the convergence rate for a discrete-time MAS with time-varying delays remains a difficult problem. To overcome the essential difficulty of switching topology, this paper aims at developing a contractive-set approach to analyze the convergence rate of a discrete-time MAS in the presence of time-varying delays and generalized coupling coefficients. Using the proposed approach, we obtain an upper bound of the convergence rate under the condition of joint connectivity. In particular, the proposed method neither requires the nonnegative property of the coupling coefficients nor the basic assumption of a uniform lower bound for all positive coupling coefficients, which have been widely applied in the existing works on this topic. As an application of the main results, we will show that the classical Vicsek model with time delays can realize synchronization if the initial topology is connected. PMID- 26357413 TI - Body-Sensor-Network-Based Spasticity Detection. AB - Spasticity is a common disorder of the skeletal muscle with a high incidence in industrialised countries. A quantitative measure of spasticity using body-worn sensors is important in order to assess rehabilitative motor training and to adjust the rehabilitative therapy accordingly. We present a new approach to spasticity detection using the Integrated Posture and Activity Network by Medit Aachen body sensor network (BSN). For this, a new electromyography (EMG) sensor node was developed and employed in human locomotion. Following an analysis of the clinical gait data of patients with unilateral cerebral palsy, a novel algorithm was developed based on the idea to detect coactivation of antagonistic muscle groups as observed in the exaggerated stretch reflex with associated joint rigidity. The algorithm applies a cross-correlation function to the EMG signals of two antagonistically working muscles and subsequent weighting using a Blackman window. The result is a coactivation index which is also weighted by the signal equivalent energy to exclude positive detection of inactive muscles. Our experimental study indicates good performance in the detection of coactive muscles associated with spasticity from clinical data as well as measurements from a BSN in qualitative comparison with the Modified Ashworth Scale as classified by clinical experts. Possible applications of the new algorithm include (but are not limited to) use in robotic sensorimotor therapy to reduce the effect of spasticity. PMID- 26357414 TI - A Distributed Computing Framework for Real-Time Detection of Stress and of Its Propagation in a Team. AB - Stress is one of the key factor that impacts the quality of our daily life: From the productivity and efficiency in the production processes to the ability of (civilian and military) individuals in making rational decisions. Also, stress can propagate from one individual to other working in a close proximity or toward a common goal, e.g., in a military operation or workforce. Real-time assessment of the stress of individuals alone is, however, not sufficient, as understanding its source and direction in which it propagates in a group of people is equally if not more-important. A continuous near real-time in situ personal stress monitoring system to quantify level of stress of individuals and its direction of propagation in a team is envisioned. However, stress monitoring of an individual via his/her mobile device may not always be possible for extended periods of time due to limited battery capacity of these devices. To overcome this challenge a novel distributed mobile computing framework is proposed to organize the resources in the vicinity and form a mobile device cloud that enables offloading of computation tasks in stress detection algorithm from resource constrained devices (low residual battery, limited CPU cycles) to resource rich devices. Our framework also supports computing parallelization and workflows, defining how the data and tasks divided/assigned among the entities of the framework are designed. The direction of propagation and magnitude of influence of stress in a group of individuals are studied by applying real-time, in situ analysis of Granger Causality. Tangible benefits (in terms of energy expenditure and execution time) of the proposed framework in comparison to a centralized framework are presented via thorough simulations and real experiments. PMID- 26357415 TI - If the Worst Happens: Five Strategies for Developing and Leveraging Information Technology-Enabled Disaster Response in Healthcare. AB - Natural disasters, such as hurricanes, tornadoes, cyclones, earthquakes, volcanic eruptions, wildfires, and floods, have a profound impact on healthcare by limiting healthcare providers' ability to effectively provide patient care in the affected areas and respond to myriad healthcare needs of the affected population. The situation can potentially be exacerbated if healthcare providers do not have effective mechanisms in place for disaster response. The response to Hurricane Katrina, a Category 3 hurricane that made landfall in August 2005 and affected several states in the southwestern U.S., was a vivid example of how the lack of effective planning and responsiveness can affect healthcare services. In this paper, based on an extensive case study, which included a rigorous examination of the Veterans Health Administration's information technology (IT) infrastructure and its response to Hurricane Katrina, we present five strategies that healthcare organizations can undertake to develop and leverage IT-enabled disaster response. These include the development of: 1) an integrated IT architecture; 2) a universal data repository; 3) web-based disaster communication and coordination; 4) an IT-enabled disaster support system; and 5) standardized and integrated IT enabled disaster response processes. We discuss how these strategies can help healthcare providers manage continuity and offer quality healthcare during natural disasters. PMID- 26357416 TI - An FDES-Based Shared Control Method for Asynchronous Brain-Actuated Robot. AB - The asynchronous brain-computer interface (BCI) offers more natural human-machine interaction. However, it is still considered insufficient to control rapid and complex sequences of movements for a robot without any advanced control method. This paper proposes a new shared controller based on the supervisory theory of fuzzy discrete event system (FDES) for brain-actuated robot control. The developed supervisory theory allows the more reliable control mode to play a dominant role in the robot control which is beneficial to reduce misoperation and improve the robustness of the system. The experimental procedures consist of real time direct manual control and BCI control tests from ten volunteers. Both tests have shown that the proposed method significantly improves the performance and robustness of the robotic control. In an online BCI experiment, eight of the participants successfully controlled the robot to circumnavigate obstacles and reached the target with a three mental states asynchronous BCI while the other two participants failed in all the BCI control sessions. Furthermore, the FDES based shared control method also helps to reduce the workload. It can be stated that the asynchronous BCI, in combination with FDES-based shared controller, is feasible for the real-time and robust control of robotics. PMID- 26357417 TI - Classifying Discriminative Features for Blur Detection. AB - Blur detection in a single image is challenging especially when the blur is spatially-varying. Developing discriminative blur features is an open problem. In this paper, we propose a new kernel-specific feature vector consisting of the information of a blur kernel and the information of an image patch. Specifically, the kernel specific-feature is composed of the multiplication of the variance of filtered kernel and the variance of filtered patch gradients. The feature origins from a blur-classification theorem and its discrimination can also be intuitively explained. To make the kernel-specific features useful for real applications, we build a pool of kernels consisting of motion-blur kernels, defocus-blur (out-of focus) kernels, and their combinations. By extracting such features followed by the classifiers, the proposed algorithm outperforms the state-of-the-art blur detection method. Experimental results on public databases demonstrate the effectiveness of the proposed method. PMID- 26357418 TI - Particle Swarm Optimization With Interswarm Interactive Learning Strategy. AB - The learning strategy in the canonical particle swarm optimization (PSO) algorithm is often blamed for being the primary reason for loss of diversity. Population diversity maintenance is crucial for preventing particles from being stuck into local optima. In this paper, we present an improved PSO algorithm with an interswarm interactive learning strategy (IILPSO) by overcoming the drawbacks of the canonical PSO algorithm's learning strategy. IILPSO is inspired by the phenomenon in human society that the interactive learning behavior takes place among different groups. Particles in IILPSO are divided into two swarms. The interswarm interactive learning (IIL) behavior is triggered when the best particle's fitness value of both the swarms does not improve for a certain number of iterations. According to the best particle's fitness value of each swarm, the softmax method and roulette method are used to determine the roles of the two swarms as the learning swarm and the learned swarm. In addition, the velocity mutation operator and global best vibration strategy are used to improve the algorithm's global search capability. The IIL strategy is applied to PSO with global star and local ring structures, which are termed as IILPSO-G and IILPSO-L algorithm, respectively. Numerical experiments are conducted to compare the proposed algorithms with eight popular PSO variants. From the experimental results, IILPSO demonstrates the good performance in terms of solution accuracy, convergence speed, and reliability. Finally, the variations of the population diversity in the entire search process provide an explanation why IILPSO performs effectively. PMID- 26357419 TI - Effect of Increased Water Intake on Urinary DNA Adduct Levels and Mutagenicity in Smokers: A Randomized Study. AB - The association between fluid intake and bladder cancer risk remains controversial. Very little is known about to which extent the amount of water intake influences the action of excreting toxics upon the urinary system. This proof of concept trial investigates the effect of water intake on mutagenesis in smokers, a high risk population for bladder cancer. METHODS: Monocentric randomized controlled trial. Inclusion Criteria. Male subjects aged 2045-45 y/o, smokers, and small drinkers (24-hour urinary volume <1 L and osmolality >700 mOsmol/kg). OUTCOMES: 4-ABP DNA adducts formation in exfoliated bladder cells in 24-hour urine collection and urinary mutagenicity in 24-hour urine. TEST GROUP: Subjects consumed 1.5 L daily of the study product (EVIAN) on top of their usual water intake for 50 days. CONTROL GROUP: Subjects continued their usual lifestyle habits. RESULTS: 65 subjects were randomized. Mean age was 30 y/o and mean cigarettes per day were 20. A slight decrease in adducts formation was observed between baseline and last visit but no statistically significant difference was demonstrated between the groups. Urinary mutagenicity significantly decreased. The study shows that increasing water intake decreases urinary mutagenicity. It is not confirmed by urinary adducts formation. Further research would be necessary. PMID- 26357420 TI - Analysis of combat sports players' injuries according to playing style for sports physiotherapy research. AB - [Purpose] This study describes the characteristics of injuries in strike and non strike combat sports, and the results are intended for use in the area of sports physiotherapy research. [Subjects and Methods] The study was conducted on 159 athletes involved in a variety of combat sports. The participants included elite college players of the following sports: judo (47), ssireum (19), wrestling (13), kendo (30), boxing (16), and taekwondo (34). Of the participants, 133 were male and 26 were female. In the case of ssireum and boxing, all of the athletes were male. [Results] In the case of the combat sports, the types of injury and injured regions differed according to playing style. Dislocation and injuries to the neck, shoulders, and elbows were more frequent in the non-strike sports, while injuries to the wrists and hands were more frequent in the strike sports. There was a high incidence of sprains, strains, bruises, and injuries to the lower limbs in both groups. [Conclusion] We suggest that the characteristics of injuries in combat sports differ according to playing style, and our study will therefore provide physical therapists and researchers with information that can be used to prevent injury. PMID- 26357421 TI - The effects of energy expenditure rate on work productivity performance at different levels of production standard time. AB - [Purpose] The purpose of this study was to investigate the effects of energy expenditure rate on work productivity performance at different levels of production standard time. [Subjects and Methods] Twenty industrial workers performed repetitive tasks at three different levels of production standard time, normal, hard, and very hard. Work productivity and energy expenditure rate were recorded during the experimental tasks. [Results] The work productivity target was not attainable for the hard and very hard production standard times. This was attributed to the energy expenditure rate, which increased as the level of production standard time became harder. The percentage change in energy expenditure rate for the very hard level (32.5%) relative to the normal level was twice that of the hard level (15.5%), indicating a higher risk of work-related musculoskeletal disorders for the harder production standard time. The energy expenditure rate for the very hard production standard time (1.36 kcal/min) was found to exceed the maximum energy expenditure rate recommended for light repetitive tasks involving both arms (1.2 kcal/min). [Conclusion] The present study shows that working with an energy expenditure rate that is either equal to or above the maximum energy expenditure rate of the tasks results in decreased work productivity performance due to the onset of physical fatigue and a higher risks of work-related musculoskeletal disorders. PMID- 26357422 TI - Effects of proprioceptive circuit exercise on knee joint pain and muscle function in patients with knee osteoarthritis. AB - [Purpose] This study applied proprioceptive circuit exercise to patients with degenerative knee osteoarthritis and examined its effects on knee joint muscle function and the level of pain. [Subjects] In this study, 14 patients with knee osteoarthritis in two groups, a proprioceptive circuit exercise group (n = 7) and control group (n = 7), were examined. [Methods] IsoMed 2000 (D&R Ferstl GmbH, Hemau, Germany) was used to assess knee joint muscle function, and a Visual Analog Scale was used to measure pain level. [Results] In the proprioceptive circuit exercise group, knee joint muscle function and pain levels improved significantly, whereas in the control group, no significant improvement was observed. [Conclusion] A proprioceptive circuit exercise may be an effective way to strengthen knee joint muscle function and reduce pain in patients with knee osteoarthritis. PMID- 26357423 TI - Therapeutic effects of reaching with forward bending of trunk on postural stability, dynamic balance, and gait in individuals with chronic hemiparetic stroke. AB - [Purpose] The objective of this study was to perform forward bending of the trunk and reaching training in chronic stroke patients and to investigate subsequent changes in trunk control, dynamic balance, and gait. [Subject] Twenty-three chronic stroke patients were randomly divided into two groups, with 10 patients in the forward bending of the trunk and reaching group and 13 patients in the control group. [Methods] Both groups underwent 30 minutes of rehabilitation therapy, five days a week, for four weeks. The forward bending of the trunk and reaching group additionally performed forward bending of the trunk and reaching training five times a week for four weeks, which involved four sets of pressing buttons 35 times, for a total of 140 button presses per session. The subjects were tested before and after training using the Trunk Impairment Scale, Berg Balance Scale, Timed Up and Go Test, Six-Minute Walking Test, and 10-Meter Walking Test. Trunk control, dynamic balance, and walking ability were compared between the two groups. [Result] The results of the study showed that the results of the Trunk Impairment Scale, Berg Balance Scale, Timed Up and Go Test, Six Minute Walking Test improved significantly in the FBR group, while there were no significant differences in the control group. [Conclusion] This study results suggest that forward bending of the trunk and reaching training can be an effective exercise method for chronic stroke patients. PMID- 26357424 TI - Effects of Nordic walking on physical functions and depression in frail people aged 70 years and above. AB - [Purpose] This study investigated the effects of Nordic walking on physical functions and depression in frail people aged 70 years and above. [Subjects] Twenty frail elderly individuals >=70 years old were assigned to either a Nordic walking group (n=8) or general exercise group (n=10). [Methods] The duration of intervention was equal in both groups (3 sessions/week for 12 weeks, 60 min/session). Physical function (balance, upper extremity strength, lower extremity strength, weakness) and depression were examined before and after the interventions. [Results] With the exception of upper extremity muscle strength, lower extremity strength, weakness, balance, and depression after Nordic walking demonstrated statistically significant improvement. However, in the general exercise group, only balance demonstrated a statistically significant improvement after the intervention. There were significant differences in the changes in lower extremity muscle strength, weakness and depression between the groups. [Conclusion] In conclusion, Nordic walking was more effective than general exercise. Therefore, we suggest that Nordic walking may be an attractive option for significant functional improvement in frail people over 70 years old. PMID- 26357425 TI - Effect of dual tasks on balance ability in stroke patients. AB - [Purpose] The purpose of this study was to determine the effects of training using dual tasks on balance ability in stroke patients. [Subjects] Forty stroke patients were divided into a dual-task training group (N = 20) and a single task training group (N = 20) randomly. [Methods] The subjects in the single-task traing group stood in a comfortable position, faced a therapist, then threw a Swiss ball back and forth. They then performed balance training in which they raised and lowered their ankles while facing forward or moved objects from one table to another. The DTG performed dual tasks, which involved performing a task on an unstable surface using a balance pad. Both groups received training 30 min per day, five times per week, for eight weeks. [Results] The DTG showed significant increases in weight distribution rate, anterior limit of stability, posterior limit of stability, and BBS scores compared with the STG. [Conclusion] According to the results of this study, dual-task training and single-task training were effective in improving balance in stroke patients, dual task training is more effective for increasing balance ability. PMID- 26357426 TI - Effects of the active release technique on pain and range of motion of patients with chronic neck pain. AB - [Purpose] To compare the influences of the active release technique (ART) and joint mobilization (JM) on the visual analog scale (VAS) pain score, pressure pain threshold (PPT), and neck range of motion (ROM) of patients with chronic neck pain. [Subjects] Twenty-four individuals with chronic neck pain were randomly and equally assigned to 3 groups: an ART group, a joint mobilization (JM) group, and a control group. Before and after the intervention, the degree of pain, PPT, and ROM of the neck were measured using a VAS, algometer, and goniometer, respectively. [Results] The ART group and JM group demonstrated significant changes in VAS and ROM between pre and post-intervention, while no significant change was observed in the control group. Significant differences in the PPT of all muscles were found in the ART group, while significant differences in all muscles other than the trapezius were found in the JM group. No significant difference in PPT was observed in any muscle of the control group. The posthoc test indicated no statistically significant difference between the ART and JM group, but the differences of variation in VAS, PPT, and ROM were greater in the ART group than in the JM and control groups. [Conclusion] ART for the treatment of chronic neck pain may be beneficial for neck pain and movement. PMID- 26357427 TI - Quantitative comparison of transient elastography (TE), shear wave elastography (SWE) and liver biopsy results of patients with chronic liver disease. AB - [Purpose] The purpose of this study was to carry out a comparitive analysis of hepatic fibrosis results of the liver hardness of patients with chronic liver disease as measured by elastography (TE), shear wave elastography (SWE), and liver biopsy. [Subjects and Methods] This study was a retrospective analysis of 304 patients who underwent SWE and TE before and after liver biopsy, taken from among patients who had been checked for liver fibrosis by liver biopsy between August 2013 and August 2014. We used receiver operating characteristic (ROC) curve to prove the diagnostic significance of liver stiffness, and then analyzed the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of SWE and TE, as well as the kappa index through cross-analysis of SWE, TE, and liver biopsy. [Results] For liver hardness, the sensitivity of SWE was 84.39%, the specificity of SWE was 97.92%, the accuracy of SWE was 87.33%, the positive predictive value of SWE was 99.32%, and the negative predictive value of SWE was 63.51%. The sensitivity of TE was 94.80%, the specificity of TE was 77.08%, the accuracy of TE was 90.95%, the positive predictive value of TE was 93.97%, and the negative predictive value of TE was 80.43%. [Conclusion] It is our opinion that SWE and TE are non-invasive methods that are more effective than the invasive methods used for diagnosing liver hardness. Invasive methods cover only a section of liver tissue, and are more likely to cause side effects during biopsy. PMID- 26357428 TI - The effect of gait training with shoe inserts on the improvement of pain and gait in sacroiliac joint patients. AB - [Purpose] The purpose of the current research was to identify how gait training with shoe inserts affects the pain and gait of sacroiliac joint dysfunction patients. [Subjects and Methods] Thirty subjects were randomly selected and assigned to be either the experimental group (gait training with shoe insert group) or control group. Each group consisted of 15 patients. Pain was measured by Visual Analogue Scale, and foot pressure in a standing position and during gait was measured with a Gateview AFA-50 system (Alpus, Seoul, Republic of Korea). A paired sample t-test was used to compare the pain and gait of the sacroiliac joint before and after the intervention. Correlation between pain and walking after gait training with shoe inserts was examined by Pearson test. The level of significance was set at alpha=0.05. [Results] It was found that application of the intervention to the experimental group resulted in a significant decrease in sacroiliac joint pain. It was also found that there was a significant correlation between Visual Analogue Scale score and dynamic asymmetric index (r= 0.796) and that there was a negative correlation between Visual Analogue Scale score and forefoot/rear foot peak pressure ratio (r= 0.728). [Conclusion] The results of our analysis lead us to conclude that the intervention with shoe inserts had a significant influence on the pain and gait of sacroiliac joint patients. PMID- 26357429 TI - The effects of Nordic and general walking on depression disorder patients' depression, sleep, and body composition. AB - [Purpose] This study examined Nordic walking as an exercise intervention for the elderly with depression. [Subjects] Twenty-four patients who were diagnosed with depression were randomly selected and divided into two groups, an experimental group which performed Nordic walking, and a control group, which performed normal walking. [Methods] Both groups practiced their respective walking exercise for 50 minutes per day, three times a week for eight weeks. To compare the effects of the intervention, psychological factors using the Beck depression inventory and sleep quality was assessed using the Korean version Pittsburgh sleep quality index. Skeletal muscle mass, fat free mass, body mass index, body fat percentage, and basal metabolism were estimated three times by a body composition analyzer, before the intervention, four weeks after the intervention, and eight weeks after the intervention. [Results] There was a significant difference in depression with a main effect of time in both groups. There was also a significant difference in sleep in over time and interaction. The differences over time between the two groups were significant for depression, sleep, and skeletal muscle mass. [Conclusion] The results suggests that Nordic walking has a positive effect on depression and sleeping disorders of the elderly, suggesting that Nordic walking based exercise programs should be developed for the elderly who suffer from depression or a sleeping disorder. PMID- 26357430 TI - The effects of gait with use of smartphone on repositioning error and curvature of the lumbar spine. AB - [Purpose] This study evaluated the effect of smartphone use on lumbar spine repositioning error and lumbar curvature while walking on a treadmill. [Subjects] A total of 20 healthy individuals (18 males and 2 females) volunteered for this study. [Methods] The subjects walked for 20 min on a treadmill while using a smartphone. To determine the effect of smartphone use, lumbar repositioning error was measured using an electronic goniometer while lumbar curvature was assessed using a Spinal Mouse before and immediately after treadmill use. Differences in the lumbar repositioning error and lumbar curvature data between the pre- and post-walking were compared using the paired t-test. [Results] The lumbar spine repositioning error was significantly greater post-walking compared with pre walking (6.70+/-2.91 degrees vs. 3.02+/-1.79 degrees ). There was no significant difference in lumbar curvature between pre- and post-walking (14.24+/-3.18 degrees vs. 13.94+/-3.12 degrees ). [Conclusion] These findings indicate that the lumbar repositioning error increased immediately after walking while using a smartphone, but that the lumbar curvature was unchanged. PMID- 26357431 TI - Upper extremity muscle tone and response of tidal volume during manually assisted breathing for patients requiring prolonged mechanical ventilation. AB - [Purpose] The aim of the present study was to examine, in patients requiring prolonged mechanical ventilation, if the response of tidal volume during manually assisted breathing is dependent upon both upper extremity muscle tone and the pressure intensity of manually assisted breathing. [Subjects] We recruited 13 patients on prolonged mechanical ventilation, and assessed their upper extremity muscle tone using the modified Ashworth scale (MAS). The subjects were assigned to either the low MAS group (MAS<=2, n=7) or the high MAS group (MAS>=3, n=6). [Methods] The manually assisted breathing technique was applied at a pressure of 2 kgf and 4 kgf. A split-plot ANOVA was performed to compare the tidal volume of each pressure during manually assisted breathing between the low and the high MAS groups. [Results] Statistical analysis showed there were main effects of the upper extremity muscle tone and the pressure intensity of the manually assisted breathing technique. There was no interaction between these factors. [Conclusion] Our findings reveal that the tidal volume during the manually assisted breathing technique for patients with prolonged mechanical ventilation depends upon the patient's upper extremity muscle tone and the pressure intensity. PMID- 26357432 TI - Effects of socks which improved foot sensation on velocity and stride length of elderly subjects crossing obstacles. AB - [Purpose] We developed socks which improve foot sensation and investigated their effect on the velocity and stride length of elderly women crossing obstacles. [Subjects] Ten community-dwelling, elderly women who could walk independently were recruited. [Methods] We measured velocity and stride length using the GAITRite system while the participants crossed obstacles under three conditions: barefoot, wearing ordinary socks, and wearing the socks which improve foot sensation. [Results] Velocity and stride length in bare feet and when wearing the sense-improving socks increased significantly compared to their values when wearing standard socks. Velocity and stride length did not differ between the bare foot and improved sock conditions. [Conclusion] Wearing socks helps protect the foot, but can decrease foot sensory input. Therefore, the socks which improve foot sensation were useful for preventing falls and protecting the feet of the elderly women while they crossed obstacles. PMID- 26357433 TI - Patients' preoperative perspectives concerning the decision to undergo total knee arthroplasty and comparison of their clinical assessments. AB - [Purpose] The aims of our study were, 1. to assess pain, limitation of movement ability, and functionality in osteoarthritis patients scheduled to undergo total knee arthroplasty, 2. to determine if pain (Group 1) or function loss (Group 2) has a greater influence on the decision of patients to have surgery, and 3. to compare results between Group 1 and Group 2. [Subject and Methods] Fifty-five osteoarthritis patients classified as grades 3 and 4 according to the Kellgren Lawrence system of classification were evaluated for preoperative pain intensity with the Visual Analogue Scale, knee flexion/extension range of movement with a clinical goniometer, and function with the Western Ontario and McMaster Universities Osteoarthritis Index. Patients were examined to reveal their reasons regarding the decision to undergo total knee arthroplasty (pain or function loss). [Results] The Visual Analog Scale scores at rest and during activity were 5.62 and 7.42, the knee flexion range of movement and extension limitation were 93.17 degrees and -7.04 degrees , and the Western Ontario and McMaster Universities Osteoarthritis Index value was 82.09. Regarding the decision to undergo surgery, 47.3% (n=26) of the knees were in Group 1, and 52.7% were in Group 2; the two groups were not significantly different. There were also no significant differences between the groups in Visual Analog Scale score during activity, the Western Ontario and McMaster Universities Osteoarthritis Index value, and knee flexion range of movement and extension limitation. The only statistically significant difference was found in the Visual Analog Scale score at rest in Group 1, which was significantly higher than that in Group 2. [Conclusion] Our results showed that osteoarthritis patients decided to undergo surgery only if all of the parameters were impaired significantly. Both pain and function loss have a similar impact on a patient's decision to undergo surgery. We observed no significant difference in clinical and self-reported outcomes between patients who decided to undergo surgery due to pain or function loss. PMID- 26357434 TI - Impact of task-oriented training on hand function and activities of daily living after stroke. AB - Purpose] We examined the improvement of hand function and activities of daily living in stroke patients after carrying out task-oriented training. [Subjects] Thirty-two patients who had been diagnosed with stroke and underwent rehabilitation therapy participated in the task-oriented training. [Methods] The participants carried out task-oriented training for 30 min per day for 4 weeks. Their hand function and activities of daily living were evaluated before and after the training. [Results] The task-oriented training had a significant impact in terms of improving hand function and activities of daily living. [Conclusion] According to the results of this study, task-oriented training resulted in improved hand function and activities of daily living in stroke patients. PMID- 26357435 TI - Relationships between menopausal syndrome and sleeping of middle-aged women. AB - [Purpose] This study aimed to examine the correlation between menopausal syndrome and sleep state of middle-aged women, and to examine the factors influencing menopausal syndrome. [Subjects] The subjects included 59 middle-aged women in Seoul, South Korea. [Methods] A cross-sectional design was adopted. The measurement tools were a general characteristics form, Menopause Symptom Index (MENSI), and sleep state scale. [Results] There was a significantly negative correlation between menopausal syndrome and sleep state of middle-aged women. The analyses showed that the prediction model was significant. The value of the adjusted R(2) was 0.279, which corresponds to an explanatory power of 27.9%. The factor found to have the most influence on menopausal syndrome of middle-aged women was sleep state, followed by sexual life satisfaction, and health status. [Conclusion] Nursing intervention programs for alleviating menopausal syndrome of middle-aged women are essential in order to improve sleep state, sexual life satisfaction, and health status. The findings from this study will contribute to help them for controlling and relieving the menopausal syndrome of middle-aged women. PMID- 26357436 TI - Complications after video-assisted thoracic surgery in patients with pulmonary nontuberculous mycobacterial lung disease who underwent preoperative pulmonary rehabilitation. AB - [Purpose] Video-assisted thoracic surgery and preoperative pulmonary rehabilitation are effective in preventing postoperative complications in patients with cardiopulmonary disease. The present study aims to elucidate the presence of postoperative pneumonia and atelectasis in patients with nontuberculous mycobacterial lung disease who underwent lung resection with video assisted thoracic surgery and preoperative pulmonary rehabilitation. [Subjects and Methods] Nineteen patients with nontuberculous mycobacterial lung disease who had undergone lung resection with video-assisted thoracic surgery and preoperative pulmonary rehabilitation were enrolled in this study. The presence of postoperative pneumonia and atelectasis was evaluated, and preoperative and postoperative pulmonary functions were compared. [Results] Postoperative pneumonia and postoperative atelectasis were not observed. Decreases of pulmonary function were 5.9% (standard deviation, 8.5) in forced vital capacity (percent predicted) and 9.6% (standard deviation, 11.1) in forced expiratory volume in 1 s (percent predicted). [Conclusion] The present study indicates that the combination of lung resection with video-assisted thoracic surgery and preoperative pulmonary rehabilitation in patients with nontuberculous mycobacterial lung disease may be effective in preventing postoperative complications. PMID- 26357437 TI - Predictive factors of hypertonia in the upper extremity of chronic stroke survivors. AB - [Purpose] Muscle tone is known to predict the motor function of the upper extremity within 12 months after onset in stroke survivors. The aim of this study was to investigate whether motor function of the upper extremity can predict the risk of hypertonia in chronic stroke survivors, and to analyze the correlation between the two variables to determine the predictive validity. [Subjects and Methods] Forty-three chronic stroke survivors were assessed using the Modified Ashworth Scale (MAS) for elbow flexor tone, the Fugl-Meyer assessment of the upper extremity (FM-UE), and the Action Research Arm Test (ARAT) for upper extremity motor recovery and function. [Results] Elbow flexor tone (MAS>=1(+)) increased by 0.246 compared with the baseline muscle tone even at month 12 and appeared to negatively affect the motor function of the upper extremity. The cutoff value for predicting muscle tone (MAS>=1(+)) was 24 for FM-UE and 15.5 for ARAT. FM-UE had the biggest impact on elbow flexor tone (MAS>=1(+)), and the risk of elbow flexor hypertonia (MAS>=1(+)) increased 0.764-fold for a cutoff value of FM-UE<=24 compared with a cutoff value of FM-UE>24. [Conclusion] The results show that the most important variable for predicting muscle tone of the elbow flexor in stroke survivors is the FM assessment of the upper extremity. PMID- 26357438 TI - Effect of exercise on the expression of nerve growth factor in the spinal cord of rats with induced osteoarthritis. AB - [Purpose] We examined the impact of exercise on the expression pattern of nerve growth factor in the spinal cord of rats with induced osteoarthritis of the knee joint. [Subjects and Methods] To produce monosodium iodoacetate-induced arthritis, rats were administered 3 mg/50 uL monosodium iodoacetate through the interarticular space of the right knee. The animals were randomly divided into four groups: rats sacrificed 3 weeks after 0.9% saline solution injection (shame group, n = 10), rats sacrificed 3 weeks after monosodium iodoacetate injection (control group, n = 10), rats with 4 weeks rest from 3 weeks after monosodium iodoacetate injection (no exercise group, n = 10), and rats with 4 weeks treadmill training from 3 weeks after monosodium iodoacetate injection (exercise group, n = 10). Serial coronal sections of the lumbar spine were cut and processed for immunohistochemistry. [Results] The expression of nerve growth factor was significantly increased in the EG compared with the SG, CG, and NEG. [Conclusion] Increased nerve growth factor expression in the spinal cord due to exercise-induced stimulation can be effective in treating chronic pain. Such treatment will contribute not only to improving the joint function of patients with chronic pain but also their quality of life. PMID- 26357439 TI - Changes in postural control between 13- and 19-year-old soccer players: is there a need for a specific therapy? AB - [Purpose] To investigate how increased training participation time and intensity affect postural control in young soccer players. [Subjects and Methods] Variability and mean velocity of sway were compared in U14 and U20 players during two-legged and one-legged quiet stances on a force plate with the player's eyes open or closed. [Results] U20 players performed much better with vision, and eyes closure considerably deteriorated their performance. The increased reliance on vision in the older group most likely resulted from the longer exposure of the U20 players to strenuous exercise, overload, and cumulative residual effects of earlier contusions. [Conclusion] These specific postural deficits in apparently healthy soccer players were found only because of objective and sensitive posturographic tests. The results of this study suggest that such tests should be regularly performed to increase the efficiency and precision of motor control evaluation in athletes. The corresponding results may help therapists mitigate the indiscernible yet detrimental changes in postural control that predispose soccer players to injury and negatively affect their performance. PMID- 26357440 TI - Analgesic effect of extracorporeal shock wave therapy versus ultrasound therapy in chronic tennis elbow. AB - [Purpose] This study compared the analgesic effects of extracorporeal shock wave therapy with those of ultrasound therapy in patients with chronic tennis elbow. [Subjects] Fifty patients with tennis elbow were randomized to receive extracorporeal shock wave therapy or ultrasound therapy. [Methods] The extracorporeal shock wave therapy group received 5 treatments once per week. Meanwhile, the ultrasound group received 10 treatments 3 times per week. Pain was assessed using the visual analogue scale during grip strength evaluation, palpation of the lateral epicondyle, Thomsen test, and chair test. Resting pain was also recorded. The scores were recorded and compared within and between groups pre-treatment, immediately post-treatment, and 3 months post-treatment. [Results] Intra- and intergroup comparisons immediately and 3 months post treatment showed extracorporeal shock wave therapy decreased pain to a significantly greater extent than ultrasound therapy. [Conclusion] Extracorporeal shock wave therapy can significantly reduce pain in patients with chronic tennis elbow. PMID- 26357441 TI - Cardiopulmonary effects of traditional Thai dance on menopausal women: a randomized controlled trial. AB - [Purpose] This study evaluated the effects of Thai dance on cardiopulmonary factors in menopausal women. [Subjects] Sixty-six menopausal women aged 40 years or more. [Methods] Subjects were randomly assigned to either the Thai dance or control group. The Thai dance group performed a traditional Thai dancing exercise program for 60 minutes, 3 times per week for 6 weeks. The control group received general health guidance. The 6-minutewalk test, peak expiratory flow, forced vital capacity, forced expiratory volume in one second, maximal voluntary ventilation, and chest expansion were assessed at baseline and at the end of the study. [Results] Sixty-six menopausal women were eligible. At the end of the study, all variables were significantly better in the Thai dance group than the control group. Moreover, all variables improved significantly compared to baseline in the Thai dance group but not in the control group. For example, the mean 6-minutewalk test result in Thai dance group at the end of the study was 285.4 m, which was significantly higher than that at baseline (254.8 m) and the control group at baseline (247.0 m). [Conclusion] A 6-week Thai dance program improves cardiorespiratory endurance in menopausal women. PMID- 26357442 TI - Effect of various hand position widths on scapular stabilizing muscles during the push-up plus exercise in healthy people. AB - [Purpose] The purpose of this study was to determine the effect of various hand position widths during the push-up plus (PUP) exercise on the activity of the scapular stabilizing muscles and other upper-extremity muscles involved in the exercise. [Subjects and Methods] Nine healthy men participated in our study. The PUP exercise was performed on a stable surface in seven different hand positions, namely shoulder width (SW), and narrower SW (NSW) and wider SW (WSW) at 10%, 20%, and 30%. Surface electromyography was used to measure the muscle activities and muscle ratio of the upper trapezius (UT), middle trapezius, lower trapezius (LT), serratus anterior (SA), pectoralis major, deltoid anterior, latissimus dorsi (LD), and triceps muscles. [Results] The SA and LD muscle activities significantly decreased in the 30% NSW and 20% WSW hand positions, respectively. The UT/LT muscle ratio significantly increased in the 30% WSW hand position. [Conclusion] The results of this study suggest that during the PUP exercise, the SW hand position should be used. In the 30% NSW hand position, the SA muscle activity decreased, and the UT/ LT ratio increased in the 30% WSW hand position. PMID- 26357443 TI - Effects of a novel walking training program with postural correction and visual feedback on walking function in patients with post-stroke hemiparesis. AB - [Purpose] This study aimed to elucidate the effects of a novel walking training program with postural correction and visual feedback on walking function in patients with post-stroke hemiparesis. [Subjects] Sixteen subjects were randomly allocated to either the experimental group (EG) or the control group (CG), with eight subjects in each. [Methods] EG and CG subjects performed a 30-min treadmill walking training exercise twice daily for 2 weeks. EG subjects also underwent postural correction using elastic bands and received visual feedback during walking. The 10-m walk test was performed, and gait parameters were measured using a gait analysis system. [Results] All parameters showed significant main effects for the group factor and time-by-group interactions. Significant main effects for the time factor were found in the stride length and stance phase ratios. [Conclusion] The novel walking training program with postural correction and visual feedback may improve walking function in patients with post-stroke hemiparesis. PMID- 26357444 TI - Mediating effect of self-control in relation to depression, stress, and activities of daily living in community residents with stroke. AB - [Purpose] This study aimed to determine whether self-control mediates the relation between depression, stress, and activities of daily living in community residents with stroke. [Subjects and Methods] This study is a secondary analysis of data from 108 community-dwelling stroke patients in Korea. Data were collected through self-reporting questionnaires, including the Korean version of the Center for Epidemiological Studies Depression Scale, Korean version of the Brief Encounter Psychosocial Instrument, and the modified Barthel index. The path model was tested to investigate causal relations between variables, obtain maximum likelihood estimates of model parameters, and provide goodness-of-fit indices. [Results] The proposed path model showed good fit to the data. Depression and stress have a significant direct effect on self-control and a significant indirect effect on activities of daily living through self-control. Depression and stress accounted for 28.0% of the variance in self-control. Depression, stress, and self-control accounted for 8.4% of the variance in explaining activities of daily living. [Conclusion] The level of self-control is an important indicator of activities of daily living in stroke patients. We suggest that interventions such as enhancement of confidence in one's self-control ability could be effective in improving the physical activity of stroke patients with depressive mood and stress. PMID- 26357445 TI - Relationship between activity limitations and participation restriction in school aged children with cerebral palsy. AB - [Purpose] This study investigated the relationship between activity limitation and participation restriction in school-aged children with cerebral palsy. [Subjects and Methods] Data were collected from 109 children with cerebral palsy aged 6-12 years. Activity limitations were assessed by using functional classification systems including the Korean-Gross Motor Function Classification System, the Korean-Manual Ability Classification System, and the Korean Communication Function Classification System. Participation restriction was measured using the Korean-Frequency of Participation Questionnaire. Physical or occupational therapists and parents collected the data. [Results] All levels of the functional classification systems were significantly negatively correlated with Korean-Frequency of Participation Questionnaire ratings (r= -0.382 to 0.477). The Korean-Frequency of Participation Questionnaire ratings differed significantly with respect to the functional classification systems; in particular, the differences in the ratings of levels I and V were significant. The Korean-Communication Function Classification System and Korean-Gross Motor Function Classification System were significant predictors of participation, explaining 26.5% of the variance. [Conclusion] Intervention programs are required to promote communication skills and gross motor ability in order to improve the participation of children with cerebral palsy. PMID- 26357446 TI - Comparison of the T10 and L4 paraspinal muscle activities over time during continuous computer work. AB - [Purpose] This study compared the T10 and L4 paraspinal muscle activities over time during continuous computer work. [Subjects] Ten male workers participated in this study. [Methods] The T10 and L4 paraspinal muscle activities were measured using a surface EMG system after 0, 20, 40, and 80 minutes of continuous computer work. [Results] The T10 and L4 paraspinal muscle activities after 20 and 40 minutes were increased significantly compared with the initial values, while they were decreased significantly after 80 minutes compared with the initial readings. [Conclusion] This study suggests that workers using computers for short periods would benefit from back muscle stretching exercises due to increased tension in these muscles. For longer computer work, strengthening exercises would be more effective than stretching due to decreased back muscle activation. PMID- 26357447 TI - Impact of decline-board squat exercises and knee joint angles on the muscle activity of the lower limbs. AB - [Purpose] This study aims to investigate how squat exercises on a decline board and how the knee joint angles affect the muscle activity of the lower limbs. [Subjects] The subjects were 26 normal adults. [Methods] A Tumble Forms wedge device was used as the decline board, and the knee joint angles were measured with a goniometer. To examine the muscle activity of the biceps femoris, rectus femoris, gastrocnemius lateralis, and tibialis anterior of the lower limbs, a comparison analysis with electromyography was conducted. [Results] The muscle activity of the biceps femoris, rectus femoris, gastrocnemius lateralis, and tibialis anterior increased with increased knee joint angles, both for squat exercises on the decline board and on a flat floor. When the knee joint angle was 45 degrees , 60 degrees , and 90 degrees , the muscle activity of the rectus femoris was significantly higher and that of the tibialis anterior was significantly lower during squat exercises on the decline board than on the flat floor. When the knee joint angle was 90 degrees , the muscle activity of the gastrocnemius lateralis was significantly lower. [Conclusion] Squat exercises on a decline board are an effective intervention to increase the muscle activity of the rectus femoris with increased knee joint angles. PMID- 26357448 TI - Repetitive sit-to-stand training with the step-foot position on the non-paretic side, and its effects on the balance and foot pressure of chronic stroke subjects. AB - [Purpose] This study aimed to improve the asymmetrical weight-bearing ratio by applying repetitive sit-to-stand training methods that feature a step-foot position to the paretic-side foot of hemiplegic patients; it sought also to provide the information needed to apply weight-bearing and balance training to hemiplegic patients. [Subjects and Methods] The subjects were divided into two groups: a spontaneous group and a step group. They all performed repetitive sit to-stand training five times per week for a total of six weeks. The Biodex Balance System, TUG, and 5XSST were used to measure the static and dynamic standing balance of each patient. A foot mat system was used to measure foot pressure. [Results] In the balance measurements, differences in the Overall index, Ant-post index, Med-lat index, Fall risk index, TUG, and 5XSST after training was significantly different between the two study groups. In evaluating foot pressure measurements, we found that the COP (Ant-post), Peak pressure: hind foot, and Contact area: hind foot measurements significantly differed between the groups after the training. [Conclusion] Repetitive sit-to-stand training that involves positioning the non-paretic leg upward can be considered a significant form of training that improves the symmetric posture adjustment and balance of hemiplegic patients following a stroke. PMID- 26357449 TI - Effect of ski simulator training on kinematic and muscle activation of the lower extremities. AB - [Purpose] This study aimed to verify the effectiveness of an augmented reality based ski simulator through analyzing the changes in movement patterns as well as the engagement of major muscles of the lower body. [Subjects] Seven subjects participated in the study. All were national team-level athletes studying at "K" Sports University in Korea who exhibited comparable performance levels and had no record of injuries in the preceding 6 months (Age 23.4 +/- 3.8 years; Height 172.6 +/- 12.1 cm; Weight 72.3 +/- 16.2 kg; Experience 12.3 +/- 4.8 years). [Methods] A reality-based ski simulator developed by a Korean manufacturer was used for the study. Three digital video cameras and a wireless electromyography system were used to perform 3-dimensional motion analysis and measure muscle activation level. [Results] Left hip angulation was found to increase as the frequency of the turns increased. Electromyography data revealed that the activation level of the quadriceps group's extension muscles and the biceps femoris group's flexing muscles had a crossing pattern. [Conclusion] Sustained training using an augmented reality-based ski simulator resulted in movements that extended the lower body joints, which is thought to contribute to increasing muscle fatigue. PMID- 26357450 TI - Effects of bridge exercise performed on an unstable surface on lumbar stabilizing muscles according to the knee angle. AB - [Purpose] This study aimed to determine the effects of bridge exercise performed on an unstable surface on lumbar stabilizing muscles according to the knee angle. [Subjects] Fifteen healthy adult men were selected for this study. [Methods] The study subjects performed the bridge exercise on an unstable surface and a stable surface, with the knees at different angles (45 degrees , 90 degrees , and 120 degrees ). An aero-step device was used as the unstable surface, and the flat ground was used as the stable surface. External oblique, internal oblique, and rectus abdominis muscle activities were assessed and compared using electromyography. [Results] The study results demonstrated that performing the bridge exercise on an unstable surface with a knee angle of 120 degrees led to a greater increase in the external oblique, internal oblique, and rectus abdominis muscle activities than when performed on a stable surface. [Conclusion] The bridge exercise with the knees at a 120 degrees angle was found to be an effective intervention for increasing the external oblique, internal oblique, and rectus abdominis muscle activities. PMID- 26357451 TI - The improvement effect of limited mental practice in individuals with poststroke hemiparesis: the influence of mental imagery and mental concentration. AB - [Purpose] This study examined whether limited mental practice improves the motor performance of poststroke individuals with hemiparesis. [Subjects] Twenty-three participants with poststroke hemiparesis (40-82 years of age) participated in this study. [Methods] The subjects were divided into four groups with respect to a dart-throwing task: the no-practice, physical practice only, mental practice only, and mental and physical practice groups. The groups were compared in terms of gains in motor performance, mental imagery vividness, and level of concentration during mental practice. [Results] No statistically significant difference was found for gains in motor performance among groups, and there was no correlation between imagery vividness and motor performance gains. However, a correlation was found between gains in motor performance and mental concentration during mental practice. [Conclusion] The results suggested that limited mental practice for individuals with poststroke hemiparesis may not improve motor performance. However, a higher degree of concentration during mental practice may improve motor performance. PMID- 26357452 TI - Efficacy of tendon and nerve gliding exercises for carpal tunnel syndrome: a systematic review of randomized controlled trials. AB - [Purpose] The purpose of this study was to assess the quality of evidence for the efficacy of tendon and nerve gliding exercises in the management of carpal tunnel syndrome. [Subjects and Methods] Four electronic databases were searched to identify randomized controlled trials on the efficacy of tendon and nerve gliding exercises for carpal tunnel syndrome. Quality assessment was conducted using the Cochrane risk of bias tool. [Results] Four trials were identified and included in the review. The results of critical appraisal of quality ranged between low and moderate risk of bias. The available data could only be included as a narrative description. Symptom severity decreased and functional status improved with combined treatment, involving a tendon or nerve gliding exercise group plus conventional treatments, compared with the use of conventional treatments alone. [Conclusion] Evidence from 4 randomized controlled trials suggests that tendon and nerve gliding exercises, when combined with conventional treatments, may have a favorable effect in patients with carpal tunnel syndrome. However, further randomized controlled trials designed to assess the effect of tendon and nerve gliding exercises alone are required to investigate the hypothesis that such exercises alleviate carpal tunnel syndrome, and to confirm and further elucidate the efficacy of standardized physical exercise programs in patients with carpal tunnel syndrome. PMID- 26357453 TI - Locality sensitivity discriminant analysis-based feature ranking of human emotion actions recognition. AB - [Purpose] Computational intelligence similar to pattern recognition is frequently confronted with high-dimensional data. Therefore, the reduction of the dimensionality is critical to make the manifold features amenable. Procedures that are analytically or computationally manageable in smaller amounts of data and low-dimensional space can become important to produce a better classification performance. [Methods] Thus, we proposed two stage reduction techniques. Feature selection-based ranking using information gain (IG) and Chi-square (Chisq) are used to identify the best ranking of the features selected for emotion classification in different actions including knocking, throwing, and lifting. Then, feature reduction-based locality sensitivity discriminant analysis (LSDA) and principal component analysis (PCA) are used to transform the selected feature to low-dimensional space. Two-stage feature selection-reduction methods such as IG-PCA, IG-LSDA, Chisq-PCA, and Chisq-LSDA are proposed. [Results] The result confirms that applying feature ranking combined with a dimensional-reduction method increases the performance of the classifiers. [Conclusion] The dimension reduction was performed using LSDA by denoting the features of the highest importance determined using IG and Chisq to not only improve the effectiveness but also reduce the computational time. PMID- 26357454 TI - Effect of the dual-wall pushup plus exercise in patients with scapular dyskinesis with a winged or tipped scapula. AB - [Purpose] This study was performed to evaluate the clinical effect of the dual wall pushup plus exercise in patients with scapular dyskinesis with a winged or tipped scapula. [Subject] A 32-year-old man with scapular dyskinesis participated in this study. [Methods] The subject performed the dual-wall pushup plus for 2 months, 4 days a week, for an average of 2 hours each day. The scapular dyskinesis test, linear distance of the acromion, acromion angle, and inferior scapular distance were evaluated before and after the exercise program. [Results] After 2 months of dual-wall pushup plus exercises, the scapular dyskinesis test was negative, the linear distance of the acromion decreased, the acromion angle increased, and the inferior scapular distance decreased compared with the initial measurements. [Conclusion] The dual-wall pushup plus exercise is an effective intervention in patients with scapular dyskinesis with a winged or tipped scapula. PMID- 26357455 TI - Muscle tone changes in the lower limbs of stroke patients induced by trunk stabilization exercises. AB - bstract. [Purpose] The purpose of this study was to identify the effects of trunk stabilization exercises on the spasticity of the lower limbs in stroke patients. [Subject] The subject of this study was a 38-year-old male patient who experienced a spontaneous intracranial hemorrhage, and had motor paralysis symptoms and spasticity on the left side. [Methods] The Hmax/Mmax ratio was measured before and after the trunk stabilization exercises, by using proprioceptive neuromuscular facilitation techniques. [Results] The Hmax/Mmax ratio changed from 37% to 20%. [Conclusion] Trunk stabilization exercises help control the muscle tone in stroke patients. PMID- 26357456 TI - Effect of thoracic movement-mediated training on back pain and trunk range of motion in a patient with lower back pain. AB - [Purpose] We explored the effect of thoracic movement-mediated training (TMMT) on back pain and trunk range of motion (ROM) in a lower back pain (LBP) patient with lumbar flexion rotation syndrome. [Subject] A 55-year-old male LBP patient with lumbar flexion rotation syndrome. [Methods] The subject underwent TMMT, consisting of two thoracic stretching exercises and three thoracic muscle strengthening exercises, supervised by a physical therapist. [Results] After training, trunk ROM increased and the visual analog scale (VAS) score of back pain decreased. [Conclusion] Therapists should consider substituting thoracic spine movements for lumbar spine movements to prevent excessive lumbar movement and pain in LBP patients with lumbar flexion rotation syndrome. PMID- 26357458 TI - A pilot study to determine if intraocular lens choice at the time of cataract surgery has an impact on patient-reported driving habits. AB - PURPOSE: To determine if intraocular lens (IOL) choice at the time of cataract surgery affects driving habits. MATERIALS AND METHODS: Pseudophakes who were 28 35 months postbilateral cataract surgery with one of two contemporary one-piece hydrophobic acrylic IOLs (SN60WF or ZCB00) were asked to complete the Driving Habits Questionnaire, a validated instrument for determining self-reported driving status, frequency, and difficulty. To determine if there were any differences in driving habits between the two groups, t-tests and chi (2) tests were used. RESULTS: Of 90 respondents, 72 (40 SN60WF and 32 ZCB00) were still active drivers. The SN60WF-implanted subjects were less likely to drive at the same speed or faster than the general flow of traffic, less likely to rate their quality of driving as average/above average, less likely to have traveled beyond their immediate neighborhood, less likely to drive at night, more likely to have moderate-to-severe difficulty driving at night, and more likely to have self reported road traffic accidents. The differences did not reach statistical significance. CONCLUSION: Changes in patients' driving habits 2-3 years after cataract surgery may be associated with the type of IOL implanted. A larger study, powered to demonstrate statistical significance, is needed to verify the trends identified in this pilot study and discover possible contributing factors. PMID- 26357457 TI - Basic Characteristics of Adults with Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Adenopathy Syndrome in Comparison with the Typical Pediatric Expression of Disease. AB - Autoinflammatory diseases are caused by inflammasome dysregulation leading to overproduction of proinflammatory cytokines and a pathological delay in the inflammation switching off. The progress of cellular biology has partially clarified pathogenic mechanisms behind monogenic autoinflammatory diseases, whereas little is known about the polygenic ones. Although the genetic susceptibility of periodic fever, aphthous stomatitis, pharyngitis, and adenopathy (PFAPA) syndrome is still obscure, the presence of overlapping symptoms with monogenic periodic fevers, the recurrence in family members, the important role played by dysregulated interleukin- (IL-) 1beta secretion during flares, the overexpression of inflammasome-associated genes during attacks, and, last but not least, the therapeutic efficacy of IL-1beta blockade strongly indicate a potential genetic involvement in its pathogenesis, probably linked with environmental factors. PFAPA syndrome has a typical inception in the pediatric age, but a delayed onset during adulthood has been described as well. Treatments required as well as effectiveness of tonsillectomy remain controversial, even if the disease seems to have a self-limited course mostly in children. The purpose of this review is to provide an overview of this complex polygenic/multifactorial autoinflammatory disorder in which the innate immune system undoubtedly plays a basic role. PMID- 26357459 TI - Long-term outcomes of limbal relaxing incisions during cataract surgery: aberrometric analysis. AB - PURPOSE: To compare the final changes in corneal wavefront aberration by limbal relaxing incisions (LRIs) after cataract surgery. METHODS: This prospective cumulative interventional nonrandomized case study included cataract and astigmatic patients undergoing LRIs and phaco with intraocular lens implantation. LRIs were planned using Donnenfeld nomogram. The root mean square of corneal wave aberration for total Z(n,i)(1<=n<=8), astigmatism Z(2,+/-1), coma Z(3-5-7,+/-1), trefoil Z(3-5-7,+/-2), spherical Z(4-6-8,0), and higher-order aberration (HOA) Z(3<=n<=8) was examined before and 3 years after surgery (optical path difference Scan II [OPD-Scan II)]. Uncorrected distance visual acuity and best-corrected distance visual acuity (CDVA) for distance, keratometric cylinder, and variations in average corneal power were also analyzed. RESULTS: Sixty-four eyes of 48 patients were included in the study. Age ranged from 42 to 92 years (70.6+/-8.4 years). After LRIs, uncorrected distance visual acuity and best-corrected distance visual acuity improved statistically (P<0.01). The keratometric cylinder value decreased by 40.1%, but analysis of KP90 and KP135 polar values did not show any decrease that could be statistically confirmed (P=0.22 and P=0.24). No significant changes were detected in root mean square of total (P=0.61) and HOAs (P=0.13) aberrations. LRIs did not induce alteration in central corneal power confirming a 1:1 coupling ratio. CONCLUSION: LRIs determined a nonsignificant alteration of corneal HOA. Therefore, LRIs can be still considered a qualitatively viable mean in those cases where toric intraocular lenses are contraindicated or not available. Yet, the authors raise the question of nonpersonalized nomograms, as in the present study, LRIs did not reach the preset target cylinder. PMID- 26357460 TI - Asthenopia in schoolchildren. AB - OBJECTIVE: To assess asthenopia prevalence and associated factors in schoolchildren aged 6-16. METHODS: This was a cross-sectional study of all children attending the first to eighth grades at two public schools in the urban region of a medium-sized town in Southern Brazil between April and December 2012. A questionnaire on socioeconomic and cultural matters was answered by parents, while the children answered a questionnaire on asthenopia-related symptoms. The children underwent a complete visual function examination, including measurement of visual acuity, refraction test, cover test, stereopsis, heterophoria assessment, near point of convergence, and accommodative convergence/accommodation ratio. RESULTS: Asthenopia prevalence was 24.7% in a total sample of 964 children. Visual acuity of 20/25 or better in both eyes was found in 92.8% of the children. The stereopsis test was normal in 99.4% of them, and some kind of strabismus was found in 3.5%. About 37.8% had astigmatism, 71.6% had mild hyperopia, 13.6% had moderate hyperopia, and 6.1% were myopic. Near point of convergence was abnormal in 14.0% of the children, and the accommodative convergence/accommodation ratio was found to be altered in 17.1% of them. CONCLUSION: Children and adolescents have expressive prevalence of asthenopia. The prevalence of visual function alterations does not differ from the general population, and, therefore, they are not prerequisites. It is very important that its mechanisms and risk factors be better defined. Health professionals need to be on the lookout for complaints of visual fatigue because of its potential to influence learning and school performance. PMID- 26357461 TI - Efficacy of a preservative-free formulation of fixed-combination bimatoprost and timolol (Ganfort PF) in treatment-naive patients vs previously treated patients. AB - PURPOSE: To evaluate, using subgroup analysis, the effect of treatment status on the intraocular pressure (IOP)-lowering efficacy of a preservative-free formulation of fixed-combination bimatoprost 0.03%/timolol 0.5% (FCBT PF). METHODS: A primary, multicenter, randomized, double-masked, 12-week study compared the efficacy and safety of FCBT PF with preserved FCBT (Ganfort((r))) in 561 patients diagnosed with glaucoma or ocular hypertension. For this analysis, eligible patients were treatment-naive or had inadequate IOP lowering and underwent a washout of previous treatment. IOP (8 am, 10 am, and 4 pm) was measured at baseline and weeks 2, 6, and 12. Subgroup analysis of the FCBT PF arm assessed changes in average eye IOP from baseline in treatment-naive vs previously treated patients. To evaluate the effect of treatment status at baseline (treatment-naive vs previously treated) on IOP reduction in the FCBT PF treatment group, an analysis of covariance model was used with treatment status and investigator as fixed effects, and baseline average eye IOP, age, glaucoma diagnosis, and baseline average eye corneal thickness as covariates. P-values and the 95% confidence intervals were determined using the model. RESULTS: In the FCBT PF arm, IOP mean changes from baseline ranged from -8.7 mmHg to -9.8 mmHg in treatment-naive patients (N=50), compared with -7.3 mmHg to -8.5 mmHg in previously treated patients (N=228). Baseline IOP, age, glaucoma diagnosis, and corneal thickness significantly affected IOP reduction in the FCBT PF group. Adjusting for these covariates, FCBT PF had a greater IOP-lowering effect (0.8 1.7 mmHg) in treatment-naive patients than previously treated patients, which was statistically significant (P<=0.05) at seven of nine time points. CONCLUSION: In this subgroup analysis, FCBT PF reduced IOP more effectively in treatment-naive than in previously treated patients possibly due, in part, to altered responsiveness or tachyphylaxis that has been associated with prior ocular hypotensive agent treatment. PMID- 26357462 TI - Insight into the mechanism of polyphenols on the activity of HMGR by molecular docking. AB - Statins are hypolipidemic drugs that are effective in the treatment of hypercholesterolemia by attenuating cholesterol synthesis in the liver via competitive inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. Recently, dietary changes associated with drug therapy have garnered attention as novel drugs to mitigate or ameliorate hypercholesterolemia. The present study was undertaken to observe different dietary polyphenols that can bind to the active site of HMGR and inhibit it. Results from the 12 dietary polyphenols tested reveal that polyphenols can bind to HMGR and block the binding of nicotinamide adenine dinucleotide phosphate (NADP(+)). We observed that the rigidity of phenolic rings prevents the polyphenols from docking to the enzyme activity site. The presence of an ester linkage between the phenolic rings in (-) epigallocatechin-3-gallate (EGCG) and the alkyl chain in curcumin allows them to orient in the active site of the HMGR and bind to the catalytic residues. EGCG and curcumin showed binding to the active site residues with a low GRID score, which may be a potential inhibitor of HMGR. Kaempferol showed binding to HMG-CoA, but with low binding affinity. These observations provide a rationale for the consistent hypolipidemic effect of EGCG and curcumin, which has been previously reported in several epidemiological and animal studies. Therefore, this study substantiates the mechanism of polyphenols on the activity of HMGR by molecular docking and provides the impetus for drug design involving further structure function relationship studies. PMID- 26357463 TI - Lipopolysaccharide-induced caveolin-1 phosphorylation-dependent increase in transcellular permeability precedes the increase in paracellular permeability. AB - BACKGROUND: Lipopolysaccharide (LPS) was shown to induce an increase in caveolin 1 (Cav-1) expression in endothelial cells; however, the mechanisms regarding this response and the consequences on caveolae-mediated transcellular transport have not been completely investigated. This study aims to investigate the role of LPS induced Cav-1 phosphorylation in pulmonary microvascular permeability in pulmonary microvascular endothelial cells (PMVECs). METHODS: Rat PMVECs were isolated, cultured, and identified. Endocytosis experiments were employed to stain the nuclei by DAPI, and images were obtained with a fluorescence microscope. Permeability of endothelial cultures was measured to analyze the barrier function of endothelial monolayer. Western blot assay was used to examine the expression of Cav-1, pCav-1, triton-insoluble Cav-1, and triton-soluble Cav-1 protein. RESULTS: The LPS treatment induced phosphorylation of Cav-1, but did not alter the total Cav-1 level till 60 min in both rat and human PMVECs. LPS treatment also increased the triton-insoluble Cav-1 level, which peaked 15 min after LPS treatment in both rat and human PMVECs. LPS treatment increases the intercellular cell adhesion molecule-1 expression. Src inhibitors, including PP2, PP1, Saracatinib, and Quercetin, partially inhibited LPS-induced phosphorylation of Cav-1. In addition, both PP2 and caveolae disruptor MbetaCD inhibited LPS induced increase of triton-insoluble Cav-1. LPS induces permeability by activating interleukin-8 and vascular endothelial growth factor and targeting other adhesion markers, such as ZO-1 and occludin. LPS treatment also significantly increased the endocytosis of albumin, which could be blocked by PP2 or MbetaCD. Furthermore, LPS treatment for 15 min significantly elevated Evans Blue-labeled BSA transport in advance of a decrease in transendothelial electrical resistance of PMVEC monolayer at this time point. After LPS treatment for 30 min, transendothelial electrical resistance decreased significantly. Moreover, PP2 and MbetaCD blocked LPS-induced increase in Evans Blue-labeled BSA level. CONCLUSION: Our study demonstrates that LPS-induced Cav-1 phosphorylation may lead to the increase of transcellular permeability prior to the increase of paracellular permeability in a Src-dependent manner. Thus, LPS-induced Cav-1 phosphorylation may be a therapeutic target for the treatment of inflammatory lung disease associated with elevated microvascular permeability. PMID- 26357464 TI - Role of chymase in the local renin-angiotensin system in keloids: inhibition of chymase may be an effective therapeutic approach to treat keloids. AB - BACKGROUND: Histologically, keloids contain excess fibroblasts and an overabundance of dermal collagen. Recently, it was reported that chymase induced a profibrotic response via transforming growth factor-beta1 (TGF-beta1)/Smad activation in keloid fibroblasts (KFs). However, the role of chymase in the local renin-angiotensin system (RAS) in keloids has not been elucidated. This study aims to determine whether chymase plays an important role in the local RAS in keloids. METHODS: We compared the expression and activity of chymase in keloids and normal skin tissues using Western blotting and radioimmunoassay, and studied the expression of TGF-beta1, interleukin-1beta, collagen I, hydroxyproline, and angiotensin II in KFs after chymase and inhibitors' treatment. RESULTS: The results revealed an increased activity of chymase in keloid tissues, and that chymase enhanced the expression of angiotensin II, collagen I, TGF-beta1, and interleukin-1beta in KFs. Blockade of the chymase pathway involved in the local RAS lowered the expression of these signaling factors. CONCLUSION: This research suggests that inhibition of chymase might be an effective therapeutic approach to improve the clinical treatment of keloids. PMID- 26357465 TI - A current review of folate receptor alpha as a potential tumor target in non small-cell lung cancer. AB - Lung cancer remains the leading common cause of cancer-related death, with non small-cell lung cancer (NSCLC) accounting for 80% of all cases. To date, platinum based doublet chemotherapy is the cornerstone of first-line therapy. However, these agents have limited use in patients who have relapsed and have metastatic disease. Therefore, novel strategies are required to improve the clinical outcome. Folate receptor alpha (FRA) is overexpressed in the majority of NSCLC, particularly in lung adenocarcinomas. FRA is largely absent from normal tissue, making it an attractive therapeutic target. In this review, we discuss FRA expression in NSCLC, conjugated FRA agents, monoclonal antibody, and FRA-specific T-cell-based therapeutic strategies aiming to improve the cure rate of FRA expressing NSCLC. PMID- 26357466 TI - Bu-Shen-Ning-Xin Decoction ameliorated the osteoporotic phenotype of ovariectomized mice without affecting the serum estrogen concentration or uterus. AB - INTRODUCTION: Bu-Shen-Ning-Xin Decoction (BSNXD), a traditional Chinese medicinal composition, has been used as a remedy for postmenopausal osteoporosis, but its effects on bone metabolism and the uterus have not been reported. PURPOSE: We aimed to determine the respective effects of BSNXD on the bones and the uterus of ovariectomized (OVX) mice to evaluate the efficacy and safety of this herbal formula. MATERIALS AND METHODS: Postmenopausal osteoporosis animal models that were generated by ovariectomy were treated with BSNXD. Dual-energy X-ray absorptiometry was performed to analyze the bone mineral density, and histomorphometric analysis was performed to measure the parameters related to bone metabolism. Calcein labeling was performed to detect bone formation. The uteruses from the mice were weighed, and the histomorphometry was analyzed. Drug derived serum was prepared to assess the 17-beta-estradiol concentration via enzyme immunoassay. RESULTS: BSNXD administration ameliorated the osteoporotic phenotype of OVX mice, as evidenced by an increase in the bone mineral density and bone volume; these effects could not be abolished by the administration of the aromatase inhibitor letrozole. Moreover, BSNXD had no effect on the serum estrogen concentration or uterus. CONCLUSION: These results suggest that BSNXD has ameliorating effects on bone loss due to estrogen deprivation without affecting the peripheral blood estrogen concentration or the uterus in OVX mice. PMID- 26357467 TI - Pharmacokinetics, pharmacodynamics, and tolerability of LC350189, a novel xanthine oxidase inhibitor, in healthy subjects. AB - INTRODUCTION: LC350189 is a novel selective xanthine oxidase inhibitor under clinical development for the management of hyperuricemia in gout patients. The aim of this study was to evaluate the pharmacokinetics, pharmacodynamics, and tolerability of the drug in healthy subjects. METHODS: A dose-block randomized, double-blind, active and placebo-controlled, single- and multiple-dosing study was conducted. A single ascending dose (SAD) study (10-600 mg) and a multiple ascending dose (MAD) study with once-daily doses (100-800 mg) for 7 days were conducted. Serial samples of blood and urine for pharmacokinetics/pharmacodynamics analysis were collected, and tolerability and adverse events were assessed throughout the study. RESULTS: Sixty-seven and 58 subjects were enrolled in the SAD and MAD studies, respectively. The mean Cmax and AUClast values increased with increasing doses, and exposure to LC350189 was dose proportional. The 24-hour mean serum uric acid (Cmean,24) decreased by 8.7% 31.7% (day 1) and 53.5%-91.2% (day 7) from baseline in the SAD and MAD studies, respectively, and the percentage decrease in Cmean,24 increased with higher doses. CONCLUSION: LC350189 was well tolerated in the dose range of 10-800 mg. It lowered the serum and urine uric acid levels substantially in this dose range; the extent of the decrease in the serum uric acid level in the 200 mg dose group was similar or higher compared to that of febuxostat 80 mg group in the MAD study. It is expected that LC350189 could be safely administered once daily to patients with hyperuricemia or gout, leading to a sufficient decrease in uric acid levels. PMID- 26357468 TI - The effect of medical illness related depression on frailty in elderly subjects with heart failure. PMID- 26357469 TI - Case finding for COPD in primary care: a qualitative study of the views of health professionals. AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is common but largely underdiagnosed. Case-finding initiatives have been evaluated in primary care, but few studies have explored the views of service providers on implementing them in practice. AIM: To explore the views of primary health care providers on case finding for COPD. METHODS: A total of 20 semi-structured interviews were conducted from March 2014 to September 2014 among general practitioners, nurses, and managers from practices participating in a large COPD case-finding trial based in primary care in the West Midlands, UK. Participants' views were sought to explore perceived benefits, harms, barriers, and facilitators to implementing COPD case finding in practice. Interviews were transcribed and analyzed using the framework method. RESULTS: Participants felt that case finding improves patient care but also acknowledged potential harms to providers (increase in workload) and to patients (overdiagnosis). Insufficient resources, poor knowledge of COPD, and limited access to diagnostic services were viewed as barriers to diagnosis, while provision of community respiratory services, including COPD specialist nurses, and support from secondary care were thought to be facilitators. Participants also expressed a need for more education on COPD for both patients and clinicians. CONCLUSION: Care providers believe that early detection of COPD improves patient care but also has accompanying harms. Barriers to diagnosing COPD, such as insufficient expertise in primary care and limited access to diagnostic services in the community, should be explored and addressed. The knowledge and attitudes of the public about COPD and its symptoms should also be investigated to inform future education and awareness-raising strategies. PMID- 26357470 TI - C-reactive protein levels in stable COPD patients: a case-control study. AB - BACKGROUND: Previous studies have documented that C-reactive protein (CRP) levels are increased in stable COPD patients. However, most studies have also shown that higher CRP levels are observed in patients with comorbidities like diabetes mellitus and cardiovascular disease. We aimed to investigate if CRP levels are increased in stable COPD patients, and if there is an association between CRP levels and pulmonary function tests and clinical characteristics. METHODS: We conducted a case-control study in a tertiary care, university-affiliated hospital. COPD patients and controls were matched for sex and age in a 2:1 matching ratio. We included only those patients who had quit smoking. CRP levels were determined and pulmonary function tests were performed in both the groups. RESULTS: A total of 60 COPD patients and 30 controls were included in the analysis. The study subjects had a mean age of 64.8+/-8.5 years in COPD group and 64.3+/-9.2 years in control group (P=0.214). The median of CRP levels was 3.17 mg/L (interquartile range [IQR]: 1.73-5.99 mg/L) in COPD group and 2.13 mg/L (IQR: 1.18-7.69 mg/L) in control group (P=0.370). There were 34 (56.7%) patients in COPD group and 14 (46.7%) patients in control group with CRP levels greater than 3 mg/dL (P=0.382). Using bivariate correlations, we found significant positive correlations in COPD patients between body mass index (BMI) and CRP (r=0.3, P=0.045), and between CRP and forced vital capacity (FVC, % of predicted) (r=-0.3; P=0.023). In a multivariate model, female sex and FVC (% of predicted) were associated with a CRP value greater than 3 mg/dL in the COPD group. CONCLUSION: The levels of CRP in the stable COPD patients were not significantly different when compared to those in the control subjects. Female sex and FVC (% predicted) were associated with CRP levels greater than 3 mg/dL in the COPD group. PMID- 26357471 TI - Core-shell nanostructured hybrid composites for volatile organic compound detection. AB - We report a high-performance chemiresistive sensor for detection of volatile organic compound (VOC) vapors based on core-shell hybridized nanostructures of Fe3O4 magnetic nanoparticles (MNPs) and poly(3,4-ethylenedioxythiophene) (PEDOT) conducting polymers. The MNPs were prepared using microwave-assisted synthesis in the presence of polymerized ionic liquids (PILs), which were used as a linker to couple the MNP and PEDOT. The resulting PEDOT-PIL-modified Fe3O4 hybrids were then explored as a sensing channel material for a chemiresistive sensor to detect VOC vapors. The PEDOT-PIL-modified Fe3O4 sensor exhibited a tunable response, with high sensitivity (down to a concentration of 1 ppm) and low noise level, to VOCs; these VOCs include acetone vapor, which is present in the exhaled breath of potential lung cancer patients. The present sensor, based on the hybrid nanostructured sensing materials, exhibited a 38.8% higher sensitivity and an 11% lower noise level than its PEDOT-PIL-only counterpart. This approach of embedding MNPs in conducting polymers could lead to the development of new electronic noses, which have significant potential for the use in the early diagnosis of lung cancer via the detection of VOC biomarkers. PMID- 26357472 TI - Silica nanoparticle-based dual imaging colloidal hybrids: cancer cell imaging and biodistribution. AB - In this study, fluorescent dye-conjugated magnetic resonance (MR) imaging agents were investigated in T mode. Gadolinium-conjugated silica nanoparticles were successfully synthesized for both MR imaging and fluorescence diagnostics. Polyamine and polycarboxyl functional groups were modified chemically on the surface of the silica nanoparticles for efficient conjugation of gadolinium ions. The derived gadolinium-conjugated silica nanoparticles were investigated by zeta potential analysis, transmission electron microscopy, inductively coupled plasma mass spectrometry, and energy dispersive x-ray spectroscopy. MR equipment was used to investigate their use as contrast-enhancing agents in T1 mode under a 9.4 T magnetic field. In addition, we tracked the distribution of the gadolinium conjugated nanoparticles in both lung cancer cells and organs in mice. PMID- 26357473 TI - Enzyme-responsive doxorubicin release from dendrimer nanoparticles for anticancer drug delivery. AB - BACKGROUND: Since cancer cells are normally over-expressed cathepsin B, we synthesized dendrimer-methoxy poly(ethylene glycol) (MPEG)-doxorubicin (DOX) conjugates using a cathepsin B-cleavable peptide for anticancer drug targeting. METHODS: Gly-Phe-Leu-Gly peptide was conjugated with the carboxylic acid end groups of a dendrimer, which was then conjugated with MPEG amine and doxorubicin by aid of carbodiimide chemistry (abbreviated as DendGDP). Dendrimer-MPEG-DOX conjugates without Gly-Phe-Leu-Gly peptide linkage was also synthesized for comparison (DendDP). Nanoparticles were then prepared using a dialysis procedure. RESULTS: The synthesized DendGDP was confirmed with (1)H nuclear magnetic resonance spectroscopy. The DendDP and DendGDP nanoparticles had a small particle size of less than 200 nm and had a spherical morphology. DendGDP had cathepsin B sensitive drug release properties while DendDP did not show cathepsin B sensitivity. Further, DendGDP had improved anticancer activity when compared with doxorubicin or DendDP in an in vivo CT26 tumor xenograft model, ie, the volume of the CT26 tumor xenograft was significantly inhibited when compared with xenografts treated with doxorubicin or DendDP nanoparticles. The DendGDP nanoparticles were found to be relatively concentrated in the tumor tissue and revealed stronger fluorescence intensity than at other body sites while doxorubicin and DendDP nanoparticles showed strong fluorescence intensity in the various organs, indicating that DendGDP has cathepsin B sensitivity. CONCLUSION: DendGDP is sensitive to cathepsin B in tumor cells and can be used as a cathepsin B-responsive drug targeting strategy. We suggest that DendGDP is a promising vehicle for cancer cell targeting. PMID- 26357475 TI - A validation of wrist actigraphy against polysomnography in patients with schizophrenia or bipolar disorder. AB - PURPOSE: Sleep disturbances are frequent in patients with schizophrenia or bipolar disorder. Actigraphy has been established as a generally reliable method to examine these disturbances across varying time spans, but the validity against polysomnography (PSG) is not well investigated for this population. We validated wrist-worn actigraphy against PSG in a population of chronic, medicated patients with schizophrenia or bipolar disorder. PATIENTS AND METHODS: From a clinical trial, we derived data from 37 patients with schizophrenia and five patients with bipolar disorder who were examined with one-night PSG and concomitant actigraphy. The following sleep variables were compared between the two methods: total sleep time, sleep efficiency, sleep latency, number of awakenings, and time awake after sleep onset. The degree of consistency between the two methods was evaluated using the intra-class correlation coefficient and Bland-Altman plots. Subgroup analyses included splitting the analyses according to sex, diagnosis, and duration of wakefulness after sleep onset. PSG was considered the gold standard. RESULTS: The intraclass correlation coefficient was high for total sleep time, moderate for the number of awakenings, and low or zero for the other examined sleep variables. These findings were reproduced in the subgroup analyses that compared men and women, as well as patients with bipolar versus schizophrenia spectrum disorders. When excluding patients with extensive periods of wakefulness after the initial sleep period (wake after sleep onset > 100 minutes), the reliability of the actigraphy-derived sleep variables markedly improved. CONCLUSION: Actigraphy reliably measures the total sleep time in this specific patient population. For patients without extensive periods of wakefulness after sleep onset, actigraphy might provide a useful measure of sleep efficiency, sleep latency, and number of awakenings. PMID- 26357474 TI - Apoptosis and necrosis induced by novel realgar quantum dots in human endometrial cancer cells via endoplasmic reticulum stress signaling pathway. AB - Realgar (AS4S4) has been used in traditional medicines for malignancy, but the poor water solubility is still a major hindrance to its clinical use. Realgar quantum dots (RQDs) were therefore synthesized with improved water solubility and bioavailability. Human endometrial cancer JEC cells were exposed to various concentrations of RQDs to evaluate their anticancer effects and to explore mechanisms by the MTT assay, transmission electron microscopy (TEM), flow cytometry, real-time reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot analysis. Results revealed that the highest photoluminescence quantum yield of the prepared RQDs was up to approximately 70%, with the average size of 5.48 nm. RQDs induced antipro-liferative activity against JEC cells in a concentration-dependent manner. In light microscopy and TEM examinations, RQDs induced vacuolization and endoplasmic reticulum (ER) dilation in JEC cells in a concentration-dependent manner. ER stress by RQDs were further confirmed by increased expression of GADD153 and GRP78 at both mRNA and protein levels. ER stress further led to JEC cell apoptosis and necrosis, as evidenced by flow cytometry and mitochondrial membrane potential detection. Our findings demonstrated that the newly synthesized RQDs were effective against human endometrial cancer cells. The underlying mechanism appears to be, at least partly, due to ER stress leading to apoptotic cell death and necrosis. PMID- 26357476 TI - Value of F-wave studies on the electrodiagnosis of carpal tunnel syndrome. AB - BACKGROUND: F waves are late electrophysiological responses to antidromic activation of motor neurons and are used to evaluate the conduction along the whole length of peripheral nerves. We aimed to determine the diagnostic efficacies of minimum median nerve F-wave latency (FWL) and median-to-ulnar nerve F-wave latency difference (FWLD) on carpal tunnel syndrome (CTS). MATERIALS AND METHODS: The electrophysiological studies consisted of sensory and motor nerve conduction and F-wave studies of the median and ulnar nerves. The best cut-off points of minimum median nerve FWL and FWLD for the diagnosis of CTS were detected for the whole study group and for different height subgroups (Group 1: 150-159 cm, Group 2: 160-169 cm, and Group 3: over 170 cm). The diagnostic efficacies of minimum median nerve FWL and FWLD were calculated for the whole CTS group and for the mild CTS group, separately. RESULTS: The best cut-off point of minimum median nerve FWL on the diagnosis of CTS was determined as 24.60 ms for the whole group. It was 23.90 ms for Group 1, 24.80 ms for Group 2, and 28.40 ms for Group 3. The usage of these stratified cut-off points yielded a higher total diagnostic efficacy rate than single cut-off point usage (79.9% vs 69%, respectively; P=0.02). The best cut-off point of FWLD on the diagnosis of CTS was 0.80 ms for the whole group. It was 0.55 ms for Group 1, 0.30 ms for Group 2, and 0.85 ms for Group 3. Both the single cutoff point usage and the stratified chart usage for FWLD had equal diagnostic efficacy (85.1%). In the mild CTS group, diagnostic efficacy was 55.5% for minimum median nerve FWL and 78.8% for FWLD (P=0.0001). CONCLUSION: Median-to-ulnar nerve FWLD yields a higher diagnostic efficacy than minimum median nerve FWL on the diagnosis of CTS. However, the sensitivities of both parameters are not satisfactory for the extremities with mild CTS, which compose the main group having diagnostic challenge. PMID- 26357477 TI - Tracheobronchial foreign bodies in children - a retrospective study of 2,000 cases in Northwestern China. AB - The aim of this study is to report our experience in the diagnosis and treatment of tracheobronchial foreign bodies (TFBs). We retrospectively reviewed medical records of 2,000 TFB patients (1,260 males and 740 females) who were treated between January 2010 and December 2013. Chest radiography and computed tomography were performed to diagnose TFBs. The location and type of foreign bodies (FBs), anesthesia methods, and treatment outcomes and complications were analyzed. Overall, 72.5% of our patients with TFB were aged between 1 years and 3 years. Plant-based FBs are the most common FB type, accounting for 91.5%. Almost 52.1% of the FBs were encountered in the right bronchus. The coincidence rate for computed tomography-based three-dimensional reconstruction was significantly greater than that for chest X-ray examination (98.7% vs 82.0%, P<0.01). Under general anesthesia, the FBs were removed by rigid bronchoscopy. Neither anesthesia complication nor intraoperative hypoxemia occurred. There were seven deaths from acute obstructive asphyxia and eight from residual FB-induced chronic asphyxia and respiration-circulation failure. In conclusion, early diagnosis and prompt treatment of TFBs with rigid bronchoscopy under general anesthesia is effective in reducing complications and mortality in affected children. PMID- 26357478 TI - National consumption of opioid and nonopioid analgesics in Croatia: 2007-2013. AB - BACKGROUND: The increased consumption of analgesics has been documented worldwide during the last 2 decades. The aim of the study was to examine the trends in opioid and nonopioid analgesic consumption in Croatia between 2007 and 2013. METHODS: Data on opioid consumption were extracted from the database of the national authority. All opioid and nonopioid analgesics were included in the analysis. Data were presented as defined daily doses per 1,000 inhabitants per day. Adequacy of opioid consumption was calculated using adequacy of consumption measure. RESULTS: During the examined 7-year period, the total consumption and total cost of all analgesics in Croatia showed continuous increase. In the M01A group (anti-inflammatory and antirheumatic products, nonsteroids), ibuprofen had an exponential increasing trend, and in 2011, it overtook diclofenac consumption. Ibuprofen and diclofenac had the highest consumption also in the M02A group of topical products for joint and muscular pain. Tramadol was by far the most consumed type of opioids (N02A group) and paracetamol in the group of other analgesics and antipyretics (N02B). The adequacy of consumption measure value was 0.19, indicating that Croatia is a country with a low opioid consumption. CONCLUSION: Between 2007 and 2013, both consumption of analgesics and their cost in Croatia had an increasing trend. Comparisons with data from other countries, based on the published literature, indicate that analgesic consumption in Croatia is still relatively low. Calculation of the adequacy of opioid consumption indicated that Croatia is a country with low opioid consumption. Further studies are necessary for establishing whether current analgesic consumption in Croatia corresponds to patient needs. PMID- 26357479 TI - Cancer risk in patients aged 30 years and above with type 2 diabetes receiving antidiabetic monotherapy: a cohort study using metformin as the comparator. AB - INTRODUCTION: Accumulating evidence suggests that metformin reduces incident cancer development. Few cohort studies have evaluated the risk of subsequent cancer development in diabetic cohorts receiving antidiabetic monotherapy. We conducted a population-based study in patients with new-onset type 2 diabetes treated with antidiabetic monotherapy. METHODS: We identified a cohort of patients with type 2 diabetics aged >=30 years receiving hypoglycemic monotherapy (n=7,325) from the 1998-2007 Longitudinal Health Insurance Dataset. Patients were grouped according to the antidiabetic therapy they received into metformin (n=2,223), sulfonylurea (n=3,965), glitazone (n=53), meglitinide (n=128), acarbose (n=150), and insulin (n=806) groups. Patients with preexisting cancer were excluded. All patients were followed up until cancer development, dropout, death, or until December 31, 2008. Cox's model was used to estimate multivariable hazard ratios (HRs) adjusted for age, sex, Charlson comorbidity index, smoking related comorbidities, alcohol use disorders, morbid obesity, pancreatitis, hypertension, monthly income, and urbanization level. The log-rank test was used to compare cumulative cancer incidence. Two-sided P-values <0.05 were required to reject the null hypothesis. RESULTS: The overall median follow-up duration was 2.5 years (interquartile range, 3.6 years). Totally, 367 and 124 cancers developed in the sulfonylurea and metformin groups, respectively, representing an adjusted HR of 1.36 (95% confidence interval [CI], 1.11-1.67; P<0.005). No significant differences were observed between other groups. Increased adjusted HRs were observed for colorectal cancer (adjusted HR, 1.94; 95% CI, 1.15-3.27; P<0.05) and lung cancer (adjusted HR, 1.76; 95% CI, 1.00-3.07; P<0.05). CONCLUSION: Metformin monotherapy may be associated with a reduction in the risk for cancer development compared with sulfonylurea monotherapy. Moreover, the use of an average defined daily dose of >0.25 of metformin when compared to lower dose will contribute to a reduction of 80% risk. PMID- 26357480 TI - Comparison of bioavailability of krill oil versus fish oil and health effect. AB - BACKGROUND: The aim of this review is to summarize the effects of krill oil (KO) or fish oil (FO) on eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) incorporation in plasma phospholipids or membrane of red blood cells (RBCs) as shown in human and animal studies. Furthermore, we discuss the findings in relation to the possible different health effects, focusing on lipids, inflammatory markers, cardiovascular disease risk, and biological functions of these two sources of long-chain n-3 polyunsaturated fatty acids (PUFAs). METHODS: A literature search was conducted in PubMed in January 2015. In total, 113 articles were identified, but based on selection criteria, 14 original papers were included in the review. RESULTS: Studies on bioavailability of EPA and DHA from KO and FO in humans and animals are limited and the interpretation is difficult, as different amounts of EPA and DHA have been used, duration of intervention differs, and different study groups have been included. Two human studies--one postprandial study and one intervention study--used the same amount of EPA and DHA from KO or FO, and they both showed that the bioavailability of EPA and DHA from KO seems to be higher than that from FO. Limited effects of KO and FO on lipids and inflammatory markers in human and animal studies were reported. Gene expression data from animal studies showed that FO upregulated the cholesterol synthesis pathway, which was the opposite of the effect mediated by KO. KO also regulated far more metabolic pathways than FO, which may indicate different biological effects of KO and FO. CONCLUSION: There seems to be a difference in bioavailability of EPA and DHA after intake of KO and FO, but more studies are needed before a firm conclusion can be made. It is also necessary to document the beneficial health effects of KO with more human studies and to elucidate if these effects differ from those after regular fish and FO intake. PMID- 26357482 TI - The prognosis factor of adjuvant radiation therapy after surgery in uterine sarcomas. AB - OBJECTIVE: This retrospective study evaluated the role of adjuvant radiotherapy (AR) after surgery in patients with uterine sarcoma and analyzed the prognostic factors of local-regional failure-free survival (LRFFS) and overall survival (OS). PATIENTS AND METHODS: A study of a total of 182 patients with uterine sarcoma was conducted between June 1994 and October 2014. Adjuvant radiotherapy was defined as postoperative external beam radiation to the pelvis (30-50 Gray/10 25 fractions at five fractions/week). The primary end point was LRFFS, and the secondary end point was OS. Kaplan-Meier curves were compared using the log-rank test. Cox regression analyses were used to determine prognosticators for LRFFS and OS. RESULTS: The median follow-up time of all patients was 75 months, with a 5-year LRFFS of 62.1%. The 2-year and 5-year LRFFS rates were longer for those who received AR than for those who did not receive AR (83.4% vs 70.3%; 78% vs 55.3%; P=0.013). The 5-year OS of all patients was 56.2%, and no significant differences were observed in the 2-year and 5-year OS rates between these two groups (82.7% vs 71.4%; 64.1% vs 51.7%; P=0.067). Importantly, in patients with leiomyosarcoma, the 2-year and 5-year LRFFS and OS rates were longer for those who received AR than for those who did not receive AR (P=0.04 and P=0.02 for the 2-year and 5-year LRFFS, respectively). CONCLUSION: Patients with uterine sarcoma who were treated with AR after surgery demonstrated an improved LRFFS compared with those who were treated with surgery alone, especially those patients with leiomyosarcoma. Therefore, the role of personalized adjuvant radiation for patients with uterine sarcoma still requires further discussion. PMID- 26357481 TI - LDL electronegativity index: a potential novel index for predicting cardiovascular disease. AB - High cardiovascular risk conditions are frequently associated with altered plasma lipoprotein profile, such as elevated low-density lipoprotein (LDL) and LDL cholesterol and decreased high-density lipoprotein. There is, however, accumulating evidence that specific subclasses of LDL may play an important role in cardiovascular disease development, and their relative concentration can be regarded as a more relevant risk factor. LDL particles undergo multiple modifications in plasma that can lead to the increase of their negative charge. The resulting electronegative LDL [LDL(-)] subfraction has been demonstrated to be especially atherogenic, and became a subject of numerous recent studies. In this review, we discuss the physicochemical properties of LDL(-), methods of its detection, atherogenic activity, and relevance of the LDL electronegativity index as a potential independent predictor of cardiovascular risk. PMID- 26357483 TI - Mesenchymal stem cell therapy for osteoarthritis: current perspectives. AB - Osteoarthritis (OA) is a painful chronic condition with a significant impact on quality of life. The societal burden imposed by OA is increasing in parallel with the aging population; however, no therapies have demonstrated efficacy in preventing the progression of this degenerative joint disease. Current mainstays of therapy include activity modification, conservative pain management strategies, weight loss, and if necessary, replacement of the affected joint. Mesenchymal stem cells (MSCs) are a multipotent endogenous population of progenitors capable of differentiation to musculoskeletal tissues. MSCs have a well-documented immunomodulatory role, managing the inflammatory response primarily through paracrine signaling. Given these properties, MSCs have been proposed as a potential regenerative cell therapy source for patients with OA. Research efforts are focused on determining the ideal source for derivation, as MSCs are native to several tissues. Furthermore, optimizing the mode of delivery remains a challenge both for appropriate localization of MSCs and for directed guidance toward stemming the local inflammatory process and initiating a regenerative response. Scaffolds and matrices with growth factor adjuvants may prove critical in this effort. The purpose of this review is to summarize the current state of MSC-based therapeutics for OA and discuss potential barriers that must be overcome for successful implementation of cell-based therapy as a routine treatment strategy in orthopedics. PMID- 26357485 TI - Evaluation of the relationship between the pelvic floor muscles and insulin resistance. AB - PURPOSE: The aim of this study was to evaluate the pelvic floor muscles (PFMs) in women with insulin resistance (IR) using surface electromyography and to associate the results with insulin levels. PATIENTS AND METHODS: Through an analytical, cross-sectional study, 86 women were evaluated and divided into two groups: a control group (n=35) and an IR group (n=51). Data were collected through detailed history-taking, physical examination, and biochemical analysis. Fasting insulin levels were used for diagnosing IR. Electromyography of the PFMs was used for analyzing the tone and maximal voluntary contraction (MVC). The measures of central tendency and linear regression models were used. RESULTS: The average age was 25.3+/-4.5 years in the IR group and 27.2+/-4.4 years in the control group. The mean weight was 75.6+/-17.6 kg and 51.8+/-4.9 kg in the IR and control groups, respectively. Fasting insulin levels were 19.7+/-6.6 uIU/mL in the IR group and 5.4+/-1.8 uIU/mL in the control group (P<0.010). There were significant differences between the groups with regard to PFM tone (IR: 13.4+/ 3.4 uV; control: 25.1+/-3.3 uV; P<0.001) and MVC (IR: 47.6+/-4.5 uV; control: 64.3+/-5.0 uV; P<0.001). Multiple linear regression analysis using the insulin levels as dependent variable showed a significant association for MVC (P=0.047), weight (P=0.017), and waist circumference (P=0.000). CONCLUSION: Compared with the control group, the IR group showed lower electromyographic activity of the PFMs, and there was an association between insulin levels and electromyographic activity. PMID- 26357484 TI - Modeling human influenza infection in the laboratory. AB - Influenza is the leading cause of death from an infectious cause. Because of its clinical importance, many investigators use animal models to understand the biologic mechanisms of influenza A virus replication, the immune response to the virus, and the efficacy of novel therapies. This review will focus on the biosafety, biosecurity, and ethical concerns that must be considered in pursuing influenza research, in addition to focusing on the two animal models - mice and ferrets - most frequently used by researchers as models of human influenza infection. PMID- 26357486 TI - Letter to the editor: "Concern regarding quantification of urinary nephrin by a commercially available ELISA". PMID- 26357488 TI - Corrigendum. PMID- 26357487 TI - Reply to "Letter to the editor: 'Concern regarding quantification of urinary nephrin by commercially available ELISA'". PMID- 26357489 TI - Pathological response rate in hormone-positive breast cancer patients treated with neoadjuvant FEC and triweekly docetaxel: a case series. AB - We recently reported that neoadjuvant 5-FU, epirubicin, and cyclophosphamide (FEC) followed by weekly paclitaxel and/or trastuzumab induced a high pathological complete response (pCR) rate in hormone-negative patients. The present study examined the therapeutic efficacy of neoadjuvant FEC followed by triweekly docetaxel and/or trastuzumab in the treatment of hormone-positive patients. Between February 2012 and December 2013, 16 hormone-positive patients with local breast cancer (luminal A type: six patients; luminal B type: two patients; luminal HER2 type: eight patients) were included in the study. The histological type of the primary cancer was invasive ductal carcinoma in all patients. The cancer stages in the 16 women who received this regimen were stage I in five (31.3%), IIA in four (25.0%), IIB in five (31.3%), IIIB in one (6.3%), and IIIC in one (6.3%). Regarding clinical TNM classification, five patients were T1N0M0, one was T1N1M0, three were T2N0M0, five were T2N1M0, one was T3N2M0, and one was T4N0M0. The pCR was evaluated using resected tissue after neoadjuvant chemotherapy according to the evaluation criteria of the Japanese Breast Cancer Society. Patients were classified into pathologic responders (grade 2: 50.0% of all patients: 2/6 of luminal A type; 6/8 of Luminal HER2 type) and nonresponders (grades 0 and 1: 50.0% of all patients: 4/6 of luminal A type; 2/2 of luminal B type; 2/8 of luminal HER2 type) according to the grade of the tumor. The pCR rate was 0%. Hematologic and nonhematologic toxicity was reversible and manageable. This study demonstrated that neoadjuvant FEC followed by triweekly docetaxel and/or trastuzumab did induce a high pathologic response in luminal HER2 type, but not in luminal A and B types, and did not induce a high pCR rate in the hormone-positive patients. PMID- 26357490 TI - Smoking and renal function in people living with human immunodeficiency virus: a Danish nationwide cohort study. AB - INTRODUCTION: Smoking is a main risk factor for morbidity and mortality in people living with human immunodeficiency virus (PLHIV), but its potential association with renal impairment remains to be established. METHODS: We did a nationwide population-based cohort study in Danish PLHIV to evaluate the association between smoking status and 1) overall renal function and risk of chronic kidney disease (CKD), 2) risk of any renal replacement therapy (aRRT), and 3) mortality following aRRT. We calculated estimated creatinine clearance using the Cockcroft Gault equation (CG-CrCl), and evaluated renal function graphically. We calculated cumulative incidence of CKD (defined as two consecutive CG-CrCls of <=60 mL/min, >=3 months apart) and aRRT and used Cox regression models to calculate incidence rate ratios (IRRs) for risk of CKD, aRRT, and mortality rate ratios (MRRs) following aRRT. RESULTS: From the Danish HIV Cohort Study, we identified 1,475 never smokers, 768 previous smokers, and 2,272 current smokers. During study period, we observed no association of smoking status with overall renal function. Previous and current smoking was not associated with increased risk of CKD (adjusted IRR: 1.1, 95% confidence interval [CI]: 0.7-1.7; adjusted IRR: 1.3, 95% CI: 0.9-1.8) or aRRT (adjusted IRR: 0.8, 95% CI: 0.4-1.7; adjusted IRR: 0.9, 95% CI: 0.5-1.7). Mortality following aRRT was high in PLHIV and increased in smokers vs never smokers (adjusted MRR: 3.8, 95% CI: 1.3-11.2). CONCLUSION: In Danish PLHIV, we observed no strong association between smoking status and renal function, risk of CKD, or risk of aRRT, but mortality was increased in smokers following aRRT. PMID- 26357492 TI - Differences in Regional Glucose Metabolism of the Brain Measured with F-18-FDG PET in Patients with Essential Tremor According to Their Response to Beta Blockers. AB - OBJECTIVE: In this study, there was an investigation as to whether there is a functional difference in essential tremor (ET), according to responses to beta blockers, by evaluating regional changes in cerebral glucose metabolism. MATERIALS AND METHODS: Seventeen male patients with ET were recruited and categorized into two groups: 8 that responded to medical therapy (group A); and 9 that did not respond to medical therapy (group B). Eleven age-sex matched healthy control male subjects were also included in this study. All subjects underwent F 18 fluorodeoxyglucose (FDG)-PET, and evaluated for their severity of tremor symptoms, which were measured as a score on the Fahn-Tolosa-Marin tremor rating scale (FTM). The FDG-PET images were analyzed using a statistical parametric mapping program. RESULTS: The mean FTM score 6 months after the initiation of propranolol therapy was significantly lower in group A (18.13 > 8.13), compared with group B (14.67 = 14.67). The glucose metabolism in group A in the left basal ganglia was seen to be decreased, compared with group B. The ET showed a more significantly decreased glucose metabolism in both the fronto-temporo-occipital lobes, precuneus of right parietal lobe, and both cerebellums compared with the healthy controls. CONCLUSION: Essential tremor is caused by electrophysiological disturbances within the cortical-cerebellar networks and degenerative process of the cerebellum. Furthermore, ET may have different pathophysiologies in terms of the origin of disease according to the response to first-line therapy. PMID- 26357491 TI - Nuclear Molecular Imaging for Vulnerable Atherosclerotic Plaques. AB - Atherosclerosis is an inflammatory disease as well as a lipid disorder. Atherosclerotic plaque formed in vessel walls may cause ischemia, and the rupture of vulnerable plaque may result in fatal events, like myocardial infarction or stroke. Because morphological imaging has limitations in diagnosing vulnerable plaque, molecular imaging has been developed, in particular, the use of nuclear imaging probes. Molecular imaging targets various aspects of vulnerable plaque, such as inflammatory cell accumulation, endothelial activation, proteolysis, neoangiogenesis, hypoxia, apoptosis, and calcification. Many preclinical and clinical studies have been conducted with various imaging probes and some of them have exhibited promising results. Despite some limitations in imaging technology, molecular imaging is expected to be used both in the research and clinical fields as imaging instruments become more advanced. PMID- 26357493 TI - Prognostic Significance of a Complete Response on Breast MRI in Patients Who Received Neoadjuvant Chemotherapy According to the Molecular Subtype. AB - OBJECTIVE: To evaluate the relationship between response categories assessed by magnetic resonance imaging (MRI) or pathology and survival outcomes, and to determine whether there are prognostic differences among molecular subtypes. MATERIALS AND METHODS: We evaluated 174 patients with biopsy-confirmed invasive breast cancer who had undergone MRI before and after neoadjuvant chemotherapy, but before surgery. Pathology findings were classified as a pathologic complete response (pCR) or a non-pCR, and MRI findings were designated as a radiologic CR (rCR) or a non-rCR. We evaluated overall and subtype-specific associations between clinicopathological factors including the assessment categories and recurrence, using the Cox proportional hazards model. RESULTS: There were 41 recurrences (9 locoregional and 32 distant recurrences). There were statistically significant differences in recurrence outcomes between patients who achieved a radiologic or a pCR and patients who did not achieve a radiologic or a pCR (recurrence hazard ratio, 11.02; p = 0.018 and recurrence hazard ratio, 3.93; p = 0.022, respectively). Kaplan-Meier curves for recurrence-free survival showed that triple-negative breast cancer was the only subtype that showed significantly better outcomes in patients who achieved a CR compared to patients who did not achieve a CR by both radiologic and pathologic assessments (p = 0.004 and 0.001, respectively). A multivariate analysis found that patients who achieved a rCR and a pCR did not display significantly different recurrence outcomes (recurrence hazard ratio, 2.02; p = 0.505 and recurrence hazard ratio, 1.12; p = 0.869, respectively). CONCLUSION: Outcomes of patients who achieved a rCR were similar to those of patients who achieved a pCR. To evaluate survival difference according to molecular subtypes, a larger study is needed. PMID- 26357494 TI - Breast Microcalcifications: Diagnostic Outcomes According to Image-Guided Biopsy Method. AB - OBJECTIVE: To evaluate the diagnostic outcomes of ultrasonography-guided core needle biopsy (US-CNB), US-guided vacuum-assisted biopsy (US-VAB), and stereotactic-guided vacuum-assisted biopsy (S-VAB) for diagnosing suspicious breast microcalcification. MATERIALS AND METHODS: We retrospectively reviewed 336 cases of suspicious breast microcalcification in patients who subsequently underwent image-guided biopsy. US-CNB was performed for US-visible microcalcifications associated with a mass (n = 28), US-VAB for US-visible microcalcifications without an associated mass (n = 59), and S-VAB for mammogram only visible lesions (n = 249). Mammographic findings, biopsy failure rate, false negative rate, and underestimation rate were analyzed. Histological diagnoses and the Breast Imaging Reporting and Data System (BI-RADS) categories were reported. RESULTS: Biopsy failure rates for US-CNB, US-VAB, and S-VAB were 7.1% (2/28), 0% (0/59), and 2.8% (7/249), respectively. Three false-negative cases were detected for US-CNB and two for S-VAB. The rates of biopsy-diagnosed ductal carcinoma in situ that were upgraded to invasive cancer at surgery were 41.7% (5/12), 12.9% (4/31), and 8.6% (3/35) for US-CNB, US-VAB, and S-VAB, respectively. Sonographically visible lesions were more likely to be malignant (66.2% [51/77] vs. 23.2% [46/198]; p < 0.001) or of higher BI-RADS category (61.0% [47/77] vs. 22.2% [44/198]; p < 0.001) than sonographically invisible lesions. CONCLUSION: Ultrasonography-guided vacuum-assisted biopsy is more accurate than US-CNB when suspicious microcalcifications are detected on US. Calcifications with malignant pathology are significantly more visible on US than benign lesions. PMID- 26357495 TI - Sonography of Invasive Apocrine Carcinoma of the Breast in Five Cases. AB - OBJECTIVE: To evaluate the sonographic features of invasive apocrine carcinoma (IAC) of the breast. MATERIALS AND METHODS: This study included five pathologically proven cases of IAC, and their sonographic features were retrospectively analyzed according to the Breast Imaging Reporting and Data System (BI-RADS) lexicon. RESULTS: All five lesions involved the left breast and were seen as irregularly shaped masses. All lesions, except one, had a parallel orientation to the chest wall. All five lesions showed noncircumscribed margins and heterogeneous echotexture; however, they showed various posterior features. One lesion had edema as an associated feature. Sonographic assessments were classified as BI-RADS category 4 in all five cases. CONCLUSION: Invasive apocrine carcinoma sonographic findings are difficult to differentiate from those of invasive ductal carcinoma of no special type. PMID- 26357496 TI - Myocardial Contrast Defect Associated with Thrombotic Coronary Occlusion: Pre Autopsy Diagnosis of a Cardiac Death with Post-Mortem CT Angiography. AB - We report the case of a female who died of suspected acute myocardial infarction. Post-mortem CT angiography (PMCTA) was performed with intravascular contrast infusion before the standard autopsy, and it successfully demonstrated the complete thrombotic occlusion of a coronary artery and also a corresponding perfusion defect on myocardium. We herein describe the PMCTA findings of a cardiac death with special emphasis on the potential benefits of this novel CT technique in forensic practice. PMID- 26357497 TI - Dynamic Contrast-Enhanced MRI Using a Macromolecular MR Contrast Agent (P792): Evaluation of Antivascular Drug Effect in a Rabbit VX2 Liver Tumor Model. AB - OBJECTIVE: To evaluate the utility of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) using macromolecular contrast agent (P792) for assessment of vascular disrupting drug effect in rabbit VX2 liver tumor models. MATERIALS AND METHODS: This study was approved by our Institutional Animal Care and Use Committee. DCE-MRI was performed with 3-T scanner in 13 VX2 liver tumor bearing rabbits, before, 4 hours after, and 24 hours after administration of vascular disrupting agent (VDA), using gadomelitol (P792, n = 7) or low molecular weight contrast agent (gadoterate meglumine [Gd-DOTA], n = 6). P792 was injected at a of dose 0.05 mmol/kg, while that of Gd-DOTA was 0.2 mmol/kg. DCE-MRI parameters including volume transfer coefficient (K(trans)) and initial area under the gadolinium concentration-time curve until 60 seconds (iAUC) of tumors were compared between the 2 groups at each time point. DCE-MRI parameters were correlated with tumor histopathology. Reproducibility in measurement of DCE-MRI parameters and image quality of source MR were compared between groups. RESULTS: P792 group showed a more prominent decrease in K(trans) and iAUC at 4 hours and 24 hours, as compared to the Gd-DOTA group. Changes in DCE-MRI parameters showed a weak correlation with histologic parameters (necrotic fraction and microvessel density) in both groups. Reproducibility of DCE-MRI parameters and overall image quality was not significantly better in the P792 group, as compared to the Gd DOTA group. CONCLUSION: Dynamic contrast-enhanced magnetic resonance imaging using a macromolecular contrast agent shows changes of hepatic perfusion more clearly after administration of the VDA. Gadolinium was required at smaller doses than a low molecular contrast agent. PMID- 26357498 TI - T2-Weighted Liver MRI Using the MultiVane Technique at 3T: Comparison with Conventional T2-Weighted MRI. AB - OBJECTIVE: To assess the value of applying MultiVane to liver T2-weighted imaging (T2WI) compared with conventional T2WIs with emphasis on detection of focal liver lesions. MATERIALS AND METHODS: Seventy-eight patients (43 men and 35 women) with 86 hepatic lesions and 20 pancreatico-biliary diseases underwent MRI including T2WIs acquired using breath-hold (BH), respiratory-triggered (RT), and MultiVane technique at 3T. Two reviewers evaluated each T2WI with respect to artefacts, organ sharpness, and conspicuity of intrahepatic vessels, hilar duct, and main lesion using five-point scales, and made pairwise comparisons between T2WI sequences for these categories. Diagnostic accuracy (Az) and sensitivity for hepatic lesion detection were evaluated using alternative free-response receiver operating characteristic analysis. RESULTS: MultiVane T2WI was significantly better than BH-T2WI or RT-T2WI for organ sharpness and conspicuity of intrahepatic vessels and main lesion in both separate reviews and pairwise comparisons (p < 0.001). With regard to motion artefacts, MultiVane T2WI or BH T2WI was better than RT-T2WI (p < 0.001). Conspicuity of hilar duct was better with BH-T2WI than with MultiVane T2WI (p = 0.030) or RT-T2WI (p < 0.001). For detection of 86 hepatic lesions, sensitivity (mean, 97.7%) of MultiVane T2WI was significantly higher than that of BH-T2WI (mean, 89.5%) (p = 0.008) or RT-T2WI (mean, 84.9%) (p = 0.001). CONCLUSION: Applying the MultiVane technique to T2WI of the liver is a promising approach to improving image quality that results in increased detection of focal liver lesions compared with conventional T2WI. PMID- 26357499 TI - Feasibility Study of Radiation Dose Reduction in Adult Female Pelvic CT Scan with Low Tube-Voltage and Adaptive Statistical Iterative Reconstruction. AB - OBJECTIVE: To evaluate image quality of female pelvic computed tomography (CT) scans reconstructed with the adaptive statistical iterative reconstruction (ASIR) technique combined with low tube-voltage and to explore the feasibility of its clinical application. MATERIALS AND METHODS: Ninety-four patients were divided into two groups. The study group used 100 kVp, and images were reconstructed with 30%, 50%, 70%, and 90% ASIR. The control group used 120 kVp, and images were reconstructed with 30% ASIR. The noise index was 15 for the study group and 11 for the control group. The CT values and noise levels of different tissues were measured. The contrast to noise ratio (CNR) was calculated. A subjective evaluation was carried out by two experienced radiologists. The CT dose index volume (CTDIvol) was recorded. RESULTS: A 44.7% reduction in CTDIvol was observed in the study group (8.18 +/- 3.58 mGy) compared with that in the control group (14.78 +/- 6.15 mGy). No significant differences were observed in the tissue noise levels and CNR values between the 70% ASIR group and the control group (p = 0.068-1.000). The subjective scores indicated that visibility of small structures, diagnostic confidence, and the overall image quality score in the 70% ASIR group was the best, and were similar to those in the control group (1.87 vs. 1.79, 1.26 vs. 1.28, and 4.53 vs. 4.57; p = 0.122-0.585). No significant difference in diagnostic accuracy was detected between the study group and the control group (42/47 vs. 43/47, p = 1.000). CONCLUSION: Low tube-voltage combined with automatic tube current modulation and 70% ASIR allowed the low CT radiation dose to be reduced by 44.7% without losing image quality on female pelvic scan. PMID- 26357500 TI - Immunoglobulin G4-Related Kidney Disease: A Comprehensive Pictorial Review of the Imaging Spectrum, Mimickers, and Clinicopathological Characteristics. AB - Immunoglobulin G4 (IgG4)-related kidney disease (IgG4-KD) has recently been demonstrated to be an important part of IgG4-related sclerosing disease (IgG4 SD). However, since IgG4-KD is still relatively unfamiliar to radiologists and physicians as compared to IgG4-SD involving other organs, it could, therefore, be easily missed. In this article, we present a comprehensive pictorial review of IgG4-KD with regards to the imaging spectrum, mimickers, and clinicopathologic characteristics, based on our clinical experience with 48 patients during the past 13 years, as well as a literature review. Awareness of the broad imaging spectrum of IgG4-KD and differential diagnosis from its mimickers will thus facilitate its early diagnosis and treatment. PMID- 26357501 TI - Does Establishing a Safety Margin Reduce Local Recurrence in Subsegmental Transarterial Chemoembolization for Small Nodular Hepatocellular Carcinomas? AB - OBJECTIVE: To test the hypothesis that a safety margin may affect local tumor recurrence (LTR) in subsegmental chemoembolization. MATERIALS AND METHODS: In 101 patients with 128 hepatocellular carcinoma (HCC) nodules (1-3 cm in size and <= 3 in number), cone-beam CT-assisted subsegmental lipiodol chemoembolization was performed. Immediately thereafter, a non-contrast thin-section CT image was obtained to evaluate the presence or absence of intra-tumoral lipiodol uptake defect and safety margin. The effect of lipiodol uptake defect and safety margin on LTR was evaluated. Univariate and multivariate analyses were performed to indentify determinant factors of LTR. RESULTS: Of the 128 HCC nodules in 101 patients, 49 (38.3%) nodules in 40 patients showed LTR during follow-up period (median, 34.1 months). Cumulative 1- and 2-year LTR rates of nodules with lipiodol uptake defect (n = 27) and those without defect (n = 101) were 58.1% vs. 10.1% and 72.1% vs. 19.5%, respectively (p < 0.001). Among the 101 nodules without a defect, the 1- and 2-year cumulative LTR rates for nodules with complete safety margin (n = 52) and those with incomplete safety margin (n = 49) were 9.8% vs. 12.8% and 18.9% vs. 19.0% (p = 0.912). In multivariate analyses, ascites (p = 0.035), indistinct tumor margin on cone-beam CT (p = 0.039), heterogeneous lipiodol uptake (p = 0.023), and intra-tumoral lipiodol uptake defect (p < 0.001) were determinant factors of higher LTR. CONCLUSION: In lipiodol chemoembolization, the safety margin in completely lipiodolized nodule without defect will not affect LTR in small nodular HCCs. PMID- 26357502 TI - Complications of Portal Vein Embolization: Evaluation on Cross-Sectional Imaging. AB - Portal vein embolization (PVE) is known as an effective and safe preoperative procedure that increases the future liver remnant (FLR) in patients with insufficient FLR. However, some possible major complications can lead to non resectability or delayed elective surgery that results in increased morbidity and mortality. Although the majority of these complications are rare, knowledge of the radiologic findings of post-procedural complications facilitate an accurate diagnosis and ensure prompt management. We accordingly reviewed the CT findings of the complications of PVE. PMID- 26357503 TI - Comparison of Multi-Echo Dixon Methods with Volume Interpolated Breath-Hold Gradient Echo Magnetic Resonance Imaging in Fat-Signal Fraction Quantification of Paravertebral Muscle. AB - OBJECTIVE: To assess whether multi-echo Dixon magnetic resonance (MR) imaging with simultaneous T2* estimation and correction yields more accurate fat-signal fraction (FF) measurement of the lumbar paravertebral muscles, in comparison with non-T2*-corrected two-echo Dixon or T2*-corrected three-echo Dixon, using the FF measurements from single-voxel MR spectroscopy as the reference standard. MATERIALS AND METHODS: Sixty patients with low back pain underwent MR imaging with a 1.5T scanner. FF mapping images automatically obtained using T2*-corrected Dixon technique with two (non-T2*-corrected), three, and six echoes, were compared with images from single-voxel MR spectroscopy at the paravertebral muscles on levels L4 through L5. FFs were measured directly by two radiologists, who independently drew the region of interest on the mapping images from the three sequences. RESULTS: A total of 117 spectroscopic measurements were performed either bilaterally (57 of 60 subjects) or unilaterally (3 of 60 subjects). The mean spectroscopic FF was 14.3 +/- 11.7% (range, 1.9-63.7%). Interobserver agreement was excellent between the two radiologists. Lin's concordance correlation between the spectroscopic findings and all the imaging based FFs were statistically significant (p < 0.001). FFs obtained from the T2* corrected six-echo Dixon sequences showed a significantly better concordance with the spectroscopic data, with its concordance correlation coefficient being 0.99 and 0.98 (p < 0.001), as compared with two- or three-echo methods. CONCLUSION: T2*-corrected six-echo Dixon sequence would be a better option than two- or three echo methods for noninvasive quantification of lumbar muscle fat quantification. PMID- 26357504 TI - Spinal Dural Arteriovenous Fistula: Imaging Features and Its Mimics. AB - Spinal dural arteriovenous fistula (SDAVF) is the most common spinal vascular malformation, however it is still rare and underdiagnosed. Magnetic resonance imaging findings such as spinal cord edema and dilated and tortuous perimedullary veins play a pivotal role in the confirmation of the diagnosis. However, spinal angiography remains the gold standard in the diagnosis of SDAVF. Classic angiographic findings of SDAVF are early filling of radicular veins, delayed venous return, and an extensive network of dilated perimedullary venous plexus. A series of angiograms of SDAVF at different locations along the spinal column, and mimics of serpentine perimedullary venous plexus on MR images, are demonstrated. Thorough knowledge of SDAVF aids correct diagnosis and prevents irreversible complications. PMID- 26357505 TI - Adaptive Statistical Iterative Reconstruction-Applied Ultra-Low-Dose CT with Radiography-Comparable Radiation Dose: Usefulness for Lung Nodule Detection. AB - OBJECTIVE: To assess the performance of adaptive statistical iterative reconstruction (ASIR)-applied ultra-low-dose CT (ULDCT) in detecting small lung nodules. MATERIALS AND METHODS: Thirty patients underwent both ULDCT and standard dose CT (SCT). After determining the reference standard nodules, five observers, blinded to the reference standard reading results, independently evaluated SCT and both subsets of ASIR- and filtered back projection (FBP)-driven ULDCT images. Data assessed by observers were compared statistically. RESULTS: Converted effective doses in SCT and ULDCT were 2.81 +/- 0.92 and 0.17 +/- 0.02 mSv, respectively. A total of 114 lung nodules were detected on SCT as a standard reference. There was no statistically significant difference in sensitivity between ASIR-driven ULDCT and SCT for three out of the five observers (p = 0.678, 0.735, < 0.01, 0.038, and < 0.868 for observers 1, 2, 3, 4, and 5, respectively). The sensitivity of FBP-driven ULDCT was significantly lower than that of ASIR driven ULDCT in three out of the five observers (p < 0.01 for three observers, and p = 0.064 and 0.146 for two observers). In jackknife alternative free response receiver operating characteristic analysis, the mean values of figure-of merit (FOM) for FBP, ASIR-driven ULDCT, and SCT were 0.682, 0.772, and 0.821, respectively, and there were no significant differences in FOM values between ASIR-driven ULDCT and SCT (p = 0.11), but the FOM value of FBP-driven ULDCT was significantly lower than that of ASIR-driven ULDCT and SCT (p = 0.01 and 0.00). CONCLUSION: Adaptive statistical iterative reconstruction-driven ULDCT delivering a radiation dose of only 0.17 mSv offers acceptable sensitivity in nodule detection compared with SCT and has better performance than FBP-driven ULDCT. PMID- 26357506 TI - CT Characteristics of Pleural Plaques Related to Occupational or Environmental Asbestos Exposure from South Korean Asbestos Mines. AB - OBJECTIVE: This study evaluated the CT characteristics of pleural plaques in asbestos-exposed individuals and compared occupational versus environmental exposure groups. MATERIALS AND METHODS: This study enrolled 181 subjects with occupational exposure and 98 with environmental exposure from chrysotile asbestos mines, who had pleural plaques confirmed by a chest CT. The CT scans were analyzed for morphological characteristics, the number and distribution of pleural plaques and combined pulmonary fibrosis. Furthermore, the CT findings were compared between the occupational and environmental exposure groups. RESULTS: Concerning the 279 subjects, the pleural plaques were single in 2.2% and unilateral in 3.6%, and showed variable widths (range, 1-20 mm; mean, 5.4 +/- 2.7 mm) and lengths (5-310 mm; 72.6 +/- 54.8 mm). The chest wall was the most commonly involved (98.6%), with an upper predominance on the ventral side (upper, 77.8% vs. lower, 55.9%, p < 0.001) and a lower predominance on the dorsal side (upper, 74.9% vs. lower, 91.8%, p = 0.02). Diaphragmatic involvement (78.1%) showed a right-side predominance (right, 73.8% vs. left, 55.6%, p < 0.001), whereas mediastinal plaques (42.7%) were more frequent on the left (right, 17.6% vs. left, 39.4%, p < 0.001). The extent and maximum length of plaques, and presence and severity of combined asbestosis, were significantly higher in the occupational exposure group (p < 0.05). CONCLUSION: Pleural plaques in asbestos exposed individuals are variable in number and size; and show a predominant distribution in the upper ventral and lower dorsal chest walls, right diaphragm, and left mediastinum. Asbestos mine workers have a higher extent of plaques and pulmonary fibrosis versus environmentally exposed individuals. PMID- 26357507 TI - Primary Pulmonary Low-Grade Angiosarcoma Characterized by Mismatch between 18F FDG PET and Dynamic Contrast-Enhanced CT. AB - We report a rare case of primary pulmonary low-grade angiosarcoma on dynamic contrast-enhanced CT and (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT imaging. A 38-year-old, asymptomatic woman was hospitalized because of an abnormality on chest radiography. A dynamic contrast-enhanced chest CT showed a 1.2 cm-sized irregular-margined nodule with strong and persistent enhancement in the right lower lobe. The lesion had low metabolic activity on an (18)F-FDG PET/CT scan. The patient underwent a wedge resection for the lesion, and pathology revealed a primary pulmonary low-grade angiosarcoma. PMID- 26357508 TI - RE: Efficacy of Cervical Interlaminar Epidural Steroid Injections. PMID- 26357510 TI - A Chaotic Particle Swarm Optimization-Based Heuristic for Market-Oriented Task Level Scheduling in Cloud Workflow Systems. AB - Cloud workflow system is a kind of platform service based on cloud computing. It facilitates the automation of workflow applications. Between cloud workflow system and its counterparts, market-oriented business model is one of the most prominent factors. The optimization of task-level scheduling in cloud workflow system is a hot topic. As the scheduling is a NP problem, Ant Colony Optimization (ACO) and Particle Swarm Optimization (PSO) have been proposed to optimize the cost. However, they have the characteristic of premature convergence in optimization process and therefore cannot effectively reduce the cost. To solve these problems, Chaotic Particle Swarm Optimization (CPSO) algorithm with chaotic sequence and adaptive inertia weight factor is applied to present the task-level scheduling. Chaotic sequence with high randomness improves the diversity of solutions, and its regularity assures a good global convergence. Adaptive inertia weight factor depends on the estimate value of cost. It makes the scheduling avoid premature convergence by properly balancing between global and local exploration. The experimental simulation shows that the cost obtained by our scheduling is always lower than the other two representative counterparts. PMID- 26357509 TI - The role of C1q in recognition of apoptotic epithelial cells and inflammatory cytokine production by phagocytes during Helicobacter pylori infection. AB - BACKGROUND: Gastric epithelial cells (GECs) undergo apoptosis during H. pylori infection and phagocytes within the mucosa engulf these cells. The recognition and clearance of apoptotic cells is a multifactorial process, enhanced by the presence of various bridging molecules and opsonins which are abundant in serum. However, it is not clear how recognition or clearance may differ in the context of H. pylori infection induced apoptosis. In addition, efferocytosis of sterile apoptotic cells is known to confer anti-inflammatory properties in the engulfing phagocyte, however it is unknown if this is maintained when phagocytes encounter H. pylori-infected cells. Thus, the ability of macrophages to bind and engulf gastric epithelial cells rendered apoptotic by H. pylori infection and the association of these interactions to the modulation of phagocyte inflammatory responses was investigated in the absence and presence of serum with a particular focus on the role of serum protein C1q. METHODS: Control (uninfected) or H. pylori-infected AGS cells were co-cultured with THP-1 macrophages in the presence or absence of serum or serum free conditions + C1q protein (40-80 MUg/mL). Binding of AGS cells to THP-1 macrophages was assessed by microscopy and cytokine (IL-6 and TNF-alpha) release from LPS stimulated THP-1 macrophages was quantified by ELISA. RESULTS: We show that macrophages bound preferentially to cells undergoing apoptosis subsequent to infection with H. pylori. Binding of apoptotic AGS to THP-1 macrophages was significantly inhibited when studied in the absence of serum and reconstitution of serum-free medium with purified human C1q restored binding of macrophages to apoptotic cells. Co-culture of sterile apoptotic and H. pylori-infected AGS cells both attenuated LPS-stimulated cytokine production by THP-1 macrophages. Further, direct treatment of THP-1 macrophages with C1q attenuated LPS stimulated TNF-alpha production. CONCLUSIONS: These studies suggest that C1q opsonizes GECs rendered apoptotic by H. pylori. No differences existed in the ability of infected or sterile apoptotic cells to attenuate macrophage cytokine production, however, there may be a direct role for C1q in modulating macrophage inflammatory cytokine production to infectious stimuli. PMID- 26357511 TI - High Intensity Focused Ultrasound versus Brachytherapy for the Treatment of Localized Prostate Cancer: A Matched-Pair Analysis. AB - Purpose. To evaluate postoperative morbidity and long term oncologic and functional outcomes of high intensity focused ultrasound (HIFU) compared to brachytherapy for the treatment of localized prostate cancer. Material and Methods. Patients treated by brachytherapy were matched 1 : 1 with patients who underwent HIFU. Differences in postoperative complications across the two groups were assessed using Wilcoxon's rank-sum or chi (2) test. Kaplan-Meier curves, log rank tests, and Cox regression models were constructed to assess differences in survival rates between the two groups. Results. Brachytherapy was significantly associated with lower voiding LUTS and less frequent acute urinary retention (p < 0.05). Median oncologic follow-up was 83 months (13-123 months) in the HIFU cohort and 44 months (13-89 months) in the brachytherapy cohort. Median time to achieve PSA nadir was statistically shorter in the HIFU. Biochemical recurrence free survival rate was significantly higher in the brachytherapy cohort compared to HIFU cohort (68.5% versus 53%, p < 0.05). No statistically significant difference in metastasis-free, cancer specific, and overall survivals was observed between the two groups. Conclusion. HIFU and brachytherapy are safe with no significant difference in cancer specific survival on long term oncologic follow-up. Nonetheless, a randomized controlled trial is needed to confirm these results. PMID- 26357512 TI - Side Effects of Chloroquine and Primaquine and Symptom Reduction in Malaria Endemic Area (Mancio Lima, Acre, Brazil). AB - Side effects of antimalarial drug can overlap with malaria symptoms. We evaluated 50 patients with vivax malaria in Mancio Lima, Acre, treated with chloroquine and primaquine. Patients were evaluated for the presence of 21 symptoms before and after treatment and for reported side effects of these drugs after treatment was started. The most frequent symptoms before medication were headache, fever, chills, sweating, arthralgia, back pain, and weakness, which were present in between 40% and 76% of respondents. The treatment reduced the occurrence of these symptoms and reduced the lack of appetite, but gastrointestinal symptoms and choluria increased in frequency. There were no reports of pale stools before medication, but 12% reported the occurrence of this symptom after treatment started. Other symptoms such as blurred vision (54%), pruritus (22%), paresthesia (6%), insomnia (46%), and "stings" into the skin (22%) were reported after chloroquine was taken. The antimalarial drugs used to treat P. vivax malaria reduce much of the systemic and algic symptoms but cause mainly gastrointestinal side effects that may lead to lack of adherence to drug treatment. It is important to guide the patient for the appearance and the transience of such side effects in order to avoid abandoning treatment. PMID- 26357513 TI - Neuroprotective Effects of Alpha-Mangostin on MPP(+)-Induced Apoptotic Cell Death in Neuroblastoma SH-SY5Y Cells. AB - In vitro studies have shown that extracts from mangosteen (Garcinia mangostana Linn.) act as antioxidants and cytoprotective agents against oxidative damage. The protective effect of alpha-mangostin, the major xanthone found in the pericarp of the mangosteen, in cellular models of Parkinson's disease (PD), has not been investigated. This study aims to investigate whether alpha-mangostin could protect SH-SY5Y neuroblastoma cells from MPP(+)-induced apoptosis. The effects of alpha-mangostin on MPP(+)-induced cell death were evaluated with a cell viability assay, staining for nuclear DNA morphology, flow cytometry for apoptotic cells and reactive oxygen species (ROS) production, quantitative real time PCR for the expression of p53, Bax, and Bcl-2, and western blot analysis for cleaved caspase-3. Concomitant treatment with alpha-mangostin attenuated the effect of MPP(+) on cell viability and apoptotic cell death. Alpha-mangostin reduced ROS formation induced by MPP(+). Bax/Bcl-2 expression ratio and expression of p53 were significantly lower in cells cocultured with alpha mangostin and MPP(+). The cotreated cells showed a significant decrease in activated caspase-3 compared with MPP(+) treatment alone. Our data suggest that cytoprotection of alpha-mangostin against MPP(+)-induced apoptosis may be associated with the reduction of ROS production, modulating the balance of pro- and antiapoptotic genes, and suppression of caspase-3 activation. PMID- 26357514 TI - The Relationship between Serum Ferritin and Insulin Resistance in Different Glucose Metabolism in Nonobese Han Adults. AB - The exact mechanism through which elevated serum ferritin promotes the development of type 2 diabetes is unknown. This study showed that ferritin concentration in impaired glucose regulation and newly diagnosed diabetes mellitus subjects of nonobesity already significantly increased when compared with normal glucose tolerant subjects of nonobesity. Elevated serum ferritin levels are associated with insulin resistance and may be not associated with the decline of insulin beta cells in different status of glucose tolerance in nonobese Han adults. PMID- 26357516 TI - Corrigendum to "Characterization of Zebrafish von Willebrand Factor Reveals Conservation of Domain Structure, Multimerization, and Intracellular Storage". AB - [This corrects the article DOI: 10.1155/2012/214209.]. PMID- 26357515 TI - Plasmablastic Lymphoma: A Review of Current Knowledge and Future Directions. AB - Plasmablastic lymphoma (PBL) is an aggressive subtype of non-Hodgkin's lymphoma (NHL), which frequently arises in the oral cavity of human immunodeficiency virus (HIV) infected patients. PBL shows diffuse proliferation of large neoplastic cells resembling B-immunoblasts/plasmablasts, or with plasmacytic features and an immunophenotype of plasma cells. PBL remains a diagnostic challenge due to its peculiar morphology and an immunohistochemical profile similar to plasma cell myeloma (PCM). PBL is also a therapeutic challenge with a clinical course characterized by a high rate of relapse and death. There is no standard chemotherapy protocol for treatment of PBL. Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP-like regimens have been the backbone while more intensive regimens such as cyclophosphamide, vincristine, doxorubicin, high-dose methotrexate/ifosfamide, etoposide, high-dose cytarabine (CODOX M/IVAC), or dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-EPOCH) are possible options. Recently, a few studies have reported the potential value of the proteasome inhibitor bortezomib and thalidomide in PBL patients. The introduction of genes encoding artificial receptors called chimeric antigen receptors (CARs) and CAR-modified T cells targeted to the B cell-specific CD19 antigen have demonstrated promising results in multiple early clinical trials. The aim of this paper is to review the recent advances in epidemiology; pathophysiology; clinical, pathologic, and molecular characteristics; therapy; and outcome in patients with PBL. PMID- 26357517 TI - Dynamic Support Culture of Murine Skeletal Muscle-Derived Stem Cells Improves Their Cardiogenic Potential In Vitro. AB - Ischemic heart disease is the main cause of death in western countries and its burden is increasing worldwide. It typically involves irreversible degeneration and loss of myocardial tissue leading to poor prognosis and fatal outcome. Autologous cells with the potential to regenerate damaged heart tissue would be an ideal source for cell therapeutic approaches. Here, we compared different methods of conditional culture for increasing the yield and cardiogenic potential of murine skeletal muscle-derived stem cells. A subpopulation of nonadherent cells was isolated from skeletal muscle by preplating and applying cell culture conditions differing in support of cluster formation. In contrast to static culture conditions, dynamic culture with or without previous hanging drop preculture led to significantly increased cluster diameters and the expression of cardiac specific markers on the protein and mRNA level. Whole-cell patch-clamp studies revealed similarities to pacemaker action potentials and responsiveness to cardiac specific pharmacological stimuli. This data indicates that skeletal muscle-derived stem cells are capable of adopting enhanced cardiac muscle cell like properties by applying specific culture conditions. Choosing this route for the establishment of a sustainable, autologous source of cells for cardiac therapies holds the potential of being clinically more acceptable than transgenic manipulation of cells. PMID- 26357518 TI - Omega-3 Fatty Acids Supplementation in Children to Prevent Asthma: Is It Worthy? A Systematic Review and Meta-Analysis. AB - Asthma is one of the most common respiratory diseases affecting all age groups. The world is now trying to identify some dietary factors which can play a preventive role. We performed this systematic review and meta-analysis of RCTs to assess the effect of intake of polyunsaturated fatty acid (PUFA) in infancy and/or childhood on incidence of asthma or wheezing episodes. We searched MEDLINE, EBSCO, Trip, and Google Scholar up to January 31, 2015. All RCTs where infants or children who were given omega-3 fatty acid supplementation and which reported incidence of asthma and/or wheezing episodes as dichotomous outcomes were included in this review. Random effects model was used for pooling the risk estimates. Total five articles were included. Most of them were from Australia. On meta-analysis, the pooled estimate of odds ratios by random effects model showed no significant change in incidence of asthma after supplementation of omega-3 FA in infancy or childhood (OR 0.974; CI 0.646, 1.469; p = 0.900). We concluded that a multicentric RCT is required to assess the effect of omega-3 FA supplementation exclusively to infants or children to predict the best time of omega-3 FA supplementation to prevent asthmatic or wheezing episodes later in life. PMID- 26357519 TI - Chemical Composition and Vasorelaxant and Antispasmodic Effects of Essential Oil from Rosa indica L. Petals. AB - Rosa indica L. belongs to the family Rosaceae and is locally known as gulaab. It has different traditional uses in cardiovascular and gastrointestinal disorders but there is no scientific data available in this regard. Therefore, the basic aim of this study was to explore the chemical composition and gastrointestinal and cardiovascular effects of the essential oil obtained from R. indica. The chemical composition of the essential oil was investigated using gas chromatography-mass spectrometry (GC-MS) technique. The cardiovascular and gastrointestinal effects were investigated using electrophysiological measurements. The GC-MS analysis of the essential oil showed various chemical components including acetic acid, mercaptohexyl ester, butanoic acid, 2-methyl-5 oxo-1-cyclopentene-1-yl ester, artemiseole, methyl santonilate, isosteviol, caryophyllene oxide, pentyl phenyl acetate, dihydromyrcene, 1,5-octadecadien, octadecanoic acid, ethyl ester, palmitic acid (2-phenyl-1,3-dioxolan-4-yl methyl ester), santolina epoxide, and 9-farnesene. The electrophysiological measurements revealed that essential oil was more potent against K(+) (80 mM) than phenylephrine precontractions using isolated rabbit aorta preparations. In isolated rabbit jejunum preparations, it showed more potency against high K(+) induced contractions than spontaneous contractions. Considering these evidences, it can be concluded that R. indica essential oil may work as a complementary and alternative medicine in gastrointestinal and cardiovascular diseases. PMID- 26357520 TI - In Vivo Delivery of Tinospora cordifolia Root Extract Preventing Radiation Induced Dystrophies in Mice Ovaries. AB - Unconscious and unplanned radiation exposures are a severe threat to gonads particularly ovaries. The present study aims at finding radioprotective effect of Tinospora cordifolia (Willd.) Miers root extract (TCRE) in ovaries. Swiss albino mice were divided into four groups: Group 1 served as "normal" and is administered double distilled water and Group 2 is given TCRE with optimum dosage selected as 75 mg/mice. Group 3 serving the purpose of "irradiated control" were exposed to 2.5 Gy gamma radiation. Group 4 (experimental) were administered optimum dosage of TCRE with prior exposure to 2.5 Gy gamma radiation. Follicle cell counts were scored at autopsy intervals of 24 hrs, 3 days, 7 days, 15 days, and 30 days after gamma irradiation. To understand the mechanism of radioprotection, lipid peroxidation (LPO) and glutathione (GSH) levels were also measured in all groups. TCRE supplementation rendered significant protection to ovaries by restoring follicle counts; it also reduced LPO levels and increased GSH levels in ovaries. It implies that TCRE administration protects ovaries against radiation exposure. PMID- 26357521 TI - Antiangiogenic Effect of Ethanol Extract of Vigna angularis via Inhibition of Phosphorylation of VEGFR2, Erk, and Akt. AB - Though dietary azuki bean (Vigna angularis) seed containing antioxidant proanthocyanidins was known to have multibiological activities including antioxidant, hypotensive, anti-inflammatory, and immunomodulatory activities, the antiangiogenic activity of ethanol extract of Vigna angularis (EVA) was never reported so far. In the present study, the antiangiogenic mechanism of EVA was examined in human umbilical vein endothelial cells (HUVECs). EVA showed weak cytotoxicity in HUVECs, while it significantly suppressed the VEGF induced proliferation of HUVECs. Consistently, wound healing assay revealed that EVA inhibited the VEGF induced migration of HUVECs. Also, EVA abrogated the VEGF induced tube formation of HUVECs in a concentration dependent fashion. Furthermore, Matrigel plug assay showed that EVA significantly reduced the hemoglobin level of Matrigel plug in mice compared to untreated control. Of note, EVA effectively attenuated the phosphorylation of VEGFR2, Erk, and Akt in VEGF treated HUVECs. Overall, our findings suggest that EVA inhibits angiogenesis in VEGF-treated HUVECs via inhibition of phosphorylation of VEGFR2, ERK, and Akt. PMID- 26357522 TI - Ozone Therapy in the Management of Persistent Radiation-Induced Rectal Bleeding in Prostate Cancer Patients. AB - Introduction. Persistent radiation-induced proctitis and rectal bleeding are debilitating complications with limited therapeutic options. We present our experience with ozone therapy in the management of such refractory rectal bleeding. Methods. Patients (n = 12) previously irradiated for prostate cancer with persistent or severe rectal bleeding without response to conventional treatment were enrolled to receive ozone therapy via rectal insufflations and/or topical application of ozonized-oil. Ten (83%) patients had Grade 3 or Grade 4 toxicity. Median follow-up after ozone therapy was 104 months (range: 52-119). Results. Following ozone therapy, the median grade of toxicity improved from 3 to 1 (p < 0.001) and the number of endoscopy treatments from 37 to 4 (p = 0.032). Hemoglobin levels changed from 11.1 (7-14) g/dL to 13 (10-15) g/dL, before and after ozone therapy, respectively (p = 0.008). Ozone therapy was well tolerated and no adverse effects were noted, except soft and temporary flatulence for some hours after each session. Conclusions. Ozone therapy was effective in radiation induced rectal bleeding in prostate cancer patients without serious adverse events. It proved useful in the management of rectal bleeding and merits further evaluation. PMID- 26357523 TI - Corrigendum to "Ethanol Extract from Ampelopsis sinica Root Exerts Anti-Hepatitis B Virus Activity via Inhibition of p53 Pathway In Vitro". AB - [This corrects the article DOI: 10.1093/ecam/neq011.]. PMID- 26357524 TI - Understanding Fibroblasts in Order to Comprehend the Osteopathic Treatment of the Fascia. AB - The osteopathic treatment of the fascia involves several techniques, each aimed at allowing the various layers of the connective system to slide over each other, improving the responses of the afferents in case of dysfunction. However, before becoming acquainted with a method, one must be aware of the structure and function of the tissue that needs treating, in order to not only better understand the manual approach, but also make a more conscious choice of the therapeutic technique to employ, in order to adjust the treatment to the specific needs of the patient. This paper examines the current literature regarding the function and structure of the fascial system and its foundation, that is, the fibroblasts. These connective cells have many properties, including the ability to contract and to communicate with one another. They play a key role in the transmission of the tension produced by the muscles and in the management of the interstitial fluids. They are a source of nociceptive and proprioceptive information as well, which is useful for proper functioning of the body system. Therefore, the fibroblasts are an invaluable instrument, essential to the understanding of the therapeutic effects of osteopathic treatment. Scientific research should make greater efforts to better understand their functioning and relationships. PMID- 26357525 TI - Lectin from green speckled lentil seeds (Lens culinaris) triggered apoptosis in nasopharyngeal carcinoma cell lines. AB - BACKGROUND: The green speckled lentil seed (Lens culinaris) lectin (GSLL) exhibits hemagglutinating activity, and possesses some properties distinct from those of other lentil lectins (e.g., molecular size, biological activities) that deserve further investigation. This study aims to investigate the basic properties (e.g., molecular size, amino acid sequence, sugar specificity) and biological activities (e.g., antiproliferative activity) of GSLL. METHODS: GSLL was purified by successive fractionation on SP-Sepharose, Affi-gel blue gel, Mono Q, and Superdex 75. The biochemical properties of GSLL were investigated by SDS PAGE, mass spectrometry, N-terminal amino acid sequencing, and sugar inhibition tests. For the biological activities, purified lyophilized GSLL was sterilized, adjusted to concentrations from 1 to 0 mg/mL (by twofold serial dilution) in Dulbecco's modified Eagle's medium with fetal bovine serum, and examined by using the MTT assay, flow cytometry, and western blotting after treatment of nasopharyngeal carcinoma CNE1 and CNE2 cell lines with the lectin. RESULTS: GSLL appeared as a 21-kDa band in non-reducing SDS-PAGE. It was composed of two subunits with molecular sizes of 17 and ~4 kDa. It exhibited specificity in binding to glucose and mannose, as well as glucosides and mannosides. Mass spectrometry and N-terminal amino acid sequencing revealed similarity of GSLL to L. culinaris lectin (LcL), especially higher coverage of the beta-chain of LcL. A 48-h treatment with GSLL exerted antiproliferative effects on nasopharyngeal carcinoma CNE1 and CNE2 cell lines with significant inhibition at 0.125 mg/mL (P < 0.001) and 1 mg/mL (P = 0.004), respectively, and these effects were attenuated in the presence of glucose and mannose. GSLL induced apoptosis in nasopharyngeal carcinoma CNE1 cells, with detectable phosphatidylserine externalization, mitochondrial depolarization, and cell cycle arrest. Western blot analysis suggested that GSLL triggered the extrinsic apoptotic pathway involving caspase 3, 8, and 9 in CNE1 cells. CONCLUSION: GSLL possessed some different properties from LcL (e.g., lower pI), and increased caspase 3, 8, and 9 activity in CNE1 cells. PMID- 26357526 TI - A new insole measurement system to detect bending and torsional moments at the human foot during footwear condition: a technical report. AB - BACKGROUND: Stress occurring at the feet while wearing footwear is often determined using pressure measurement systems. However, other forms of stress, such as bending, torsional and shear loadings, cannot be detected in shoes during day-to-day activities. Nevertheless, the detection of these types of stresses would be helpful for understanding the mechanical aspects of various kinds of hard and soft tissue injuries. Therefore, we describe the development of a new measuring device that allows the reliable determination of bending and torsional load at the foot in shoes. METHODS: The system consists of a measuring insole and an analogue device with Bluetooth interface. The specific shape of the insole base layer, the positions of the strain gauges, and the interconnections between them have all been selected in such a way so as to isolate bending and torsional moment detections in the medial and lateral metatarsal region. The system was calibrated using a classical two-point test procedure. A single case study was executed to evaluate the new device for practical use. This application consisted of one subject wearing neutral shoes walking on a treadmill. RESULTS: The calibration results (coefficients of determination R(2) > 0.999) show that bending and torsional load can be reliably detected using the measurement system presented. In the single case study, alternating bending and torsional load can be detected during walking, and the shape of the detected bending moments can be confirmed by the measurements of Arndt et al. (J Biomech 35:621-8, 2002). CONCLUSIONS: Despite some limitations, the presented device allows for the reliable determination of bending and torsional stresses at the foot in shoes. PMID- 26357527 TI - Musical patterns for comparative epigenomics. AB - Scientific data has been transformed into music in order to raise awareness in the non-scientific community. While the general public is nowadays familiar with the genetic code, there is still a lack of knowledge regarding epigenetic regulation. By making use of the binary nature of the methylome, we here describe a method that transforms methylation patterns into music. The resulting musical pieces show decent complexity and allow the audible recognition between music and underlying methylation state. This approach might therefore facilitate the recognition of complex methylation patterns and increase awareness for epigenetic regulation in the general public. PMID- 26357528 TI - Patient Care Planning Discussions for Patients at the End of Life: An Evidence Based Analysis. AB - BACKGROUND: Ontario spends about 9% of its health budget on care for people at the end of life (EoL), most of whom die from chronic, prolonged conditions. For many people, patient care planning discussions (PCPDs) can improve the quality and reduce the cost of care. OBJECTIVES: This evidence-based analysis aimed to examine the effectiveness of PCPDs in achieving better patient-centred outcomes for people at the EoL. DATA SOURCES: A systematic literature search was conducted in MEDLINE, Embase, CINAHL, and EBM Reviews to identify relevant literature published between January 1, 2004, and October 9, 2013. REVIEW METHODS: Peer reviewed reports from randomized controlled trials (RCTs) and observational studies were examined. Outcomes included quality of life (QoL), satisfaction, concordance, advance care planning (ACP), and health care use. Quality of evidence was assessed using GRADE. RESULTS: While the effects of PCPDs on QoL are unclear, single-provider PCPDs were associated with family members being very satisfied with EoL care (odds ratio [OR]: 5.17 [95% CI: 1.52, 17.58]), improved concordance between patients' and families' wishes (OR: 4.32, P < 0.001), fewer episodes of hospital care (mean difference [MD]: -0.21, P = 0.04), spending fewer days in hospital (MD: -1.8, P = 0.03), and receiving hospice care (OR: 5.17 [95% CI: 2.03, 13.17]). Team-based PCPDs were associated with greater patient satisfaction (standardized mean difference [SMD]: 0.39 [95% CI: 0.17, 0.60]) and fewer outpatient visits (MD: -5.20 [95% CI: -9.70, -0.70]). Overall, PCPDs were associated with more ACP and more optimal health care use. LIMITATIONS: Most of the RCTs were unblinded, intervention was measured or described inadequately in some studies, and the term "usual care" was often undefined. CONCLUSIONS: Patients at the EoL and their families benefited from PCPDs. Furthermore, PCPDs occurring earlier in the course of illness were associated with better outcomes than those occurring later. PMID- 26357529 TI - Capsule Endoscopy in the Assessment of Obscure Gastrointestinal Bleeding: An Evidence-Based Analysis. AB - BACKGROUND: Obscure gastrointestinal bleeding (OGIB) is defined as persistent or recurrent bleeding associated with negative findings on upper and lower gastrointestinal (GI) endoscopic evaluations. The diagnosis and management of patients with OGIB is particularly challenging because of the length and complex loops of the small intestine. Capsule endoscopy (CE) is 1 diagnostic modality that is used to determine the etiology of bleeding. OBJECTIVES: The objective of this analysis was to review the diagnostic accuracy, safety, and impact on health outcomes of CE in patients with OGIB in comparison with other diagnostic modalities. DATA SOURCES: A literature search was performed using Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid Embase, the Wiley Cochrane Library, and the Centre for Reviews and Dissemination database, for studies published between 2007 and 2013. REVIEW METHODS: Data on diagnostic accuracy, safety, and impact on health outcomes were abstracted from included studies. Quality of evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation (GRADE). RESULTS: The search yielded 1,189 citations, and 24 studies were included. Eight studies reported diagnostic accuracy comparing CE with other diagnostic modalities. Capsule endoscopy has a higher sensitivity and lower specificity than magnetic resonance enteroclysis, computed tomography, and push enteroscopy. Capsule endoscopy has a good safety profile with few adverse events, although comparative safety data with other diagnostic modalities are limited. Capsule endoscopy is associated with no difference in patient health-related outcomes such as rebleeding or follow-up treatment compared with push enteroscopy, small-bowel follow-through, and angiography. LIMITATIONS: There was significant heterogeneity in estimates of diagnostic accuracy, which prohibited a statistical summary of findings. The analysis was also limited by the fact that there is no established reference standard to which the diagnostic accuracy of CE can be compared. CONCLUSIONS: There is very-low-quality evidence that CE has a higher sensitivity but a lower specificity than other diagnostic modalities. Capsule endoscopy has few adverse events, with capsule retention being the most serious complication. Capsule endoscopy is perceived by patients as less painful and less burdensome compared with other modalities. There is low-quality evidence that patients who undergo CE have similar rates of rebleeding, further therapeutic interventions, and hospitalization compared with other diagnostic modalities. PMID- 26357532 TI - Deoxyinosine repair in nuclear extracts of human cells. AB - BACKGROUND: Deamination of adenine can occur spontaneously under physiological conditions generating the highly mutagenic lesion, hypoxanthine. This process is enhanced by ROS from exposure of DNA to ionizing radiation, UV light, nitrous acid, or heat. Hypoxanthine in DNA can pair with cytosine which results in A:T to G:C transition mutations after DNA replication. In Escherichia coli, deoxyinosine (hypoxanthine deoxyribonucleotide, dI) is removed through an alternative excision repair pathway initiated by endonuclease V. However, the correction of dI in mammalian cells appears more complex and was not fully understood. RESULTS: All four possible dI-containing heteroduplex DNAs, including A-I, C-I, G-I, and T-I were introduced to repair reactions containing extracts from human cells. The repair reaction requires magnesium, dNTPs, and ATP as cofactors. We found G-I was the best substrate followed by T-I, A-I and C-I, respectively. Moreover, judging from the repair requirements and sensitivity to specific polymerase inhibitors, there were overlapping repair activities in processing of dI in DNA. Indeed, a hereditable non-polyposis colorectal cancer cell line (HCT116) demonstrated lower dI repair activity that was partially attributed to lack of mismatch repair. CONCLUSIONS: A plasmid-based convenient and non-radioisotopic method was created to study dI repair in human cells. Mutagenic dI lesions processed in vitro can be scored by restriction enzyme cleavage to evaluate the repair. The repair assay described in this study provides a good platform for further investigation of human repair pathways involved in dI processing and their biological significance in mutation prevention. PMID- 26357531 TI - Magnetic Resonance-Guided High-Intensity Focused Ultrasound (MRgHIFU) for Treatment of Symptomatic Uterine Fibroids: An Economic Analysis. AB - BACKGROUND: Uterine fibroids, or leiomyomas, are the most common benign tumours in women of childbearing age. Some women experience symptoms (e.g., heavy bleeding) that require aggressive forms of treatment such as uterine artery embolization (UAE), myomectomy, magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU), and even hysterectomy. It is important to note that hysterectomy is not appropriate for women who desire future childbearing. OBJECTIVES: The objective of this analysis was to evaluate the cost-effectiveness and budgetary impact of implementing MRgHIFU as a treatment option for symptomatic uterine fibroids in premenopausal women for whom drugs have been ineffective. REVIEW METHODS: We performed an original cost-effectiveness analysis to assess the long-term costs and effects of MRgHIFU compared with hysterectomy, myomectomy, and UAE as a strategy for treating symptomatic uterine fibroids in premenopausal women aged 40 to 51 years. We explored a number of scenarios, e.g., comparing MRgHIFU with uterine-preserving procedures only, considering MRgHIFU eligible patients only, and eliminating UAE as a treatment option. In addition, we performed a one-year budget impact analysis, using data from Ontario administrative sources. Four scenarios were explored in the budgetary impact analysis: *MRgHIFU funded at 2 centres *MRgHIFU funded at 2 centres and replacing only uterine-preserving procedures *MRgHIFU funded at 6 centres *MRgHIFU funded at 6 centres and replacing only uterine-preserving procedures Analyses were conducted from the Ontario public payer perspective. RESULTS: The base case determined that the uterine artery embolization (UAE) treatment strategy was the cost-effective option at commonly accepted willingness-to-pay values. Compared with hysterectomy, UAE was calculated as having an incremental cost-effectiveness ratio (ICER) of $46,480 per quality-adjusted life-year (QALY) gained. The MRgHIFU strategy was extendedly dominated by a combination of UAE and hysterectomy, and myomectomy was strictly dominated by MRgHIFU and UAE. In the scenario where only MRgHIFU-eligible patients were considered, MRgHIFU was the cost-effective option for a willingness-to-pay threshold of $50,000. In the scenario where only MRgHIFU eligible patients were considered and where UAE was eliminated as a treatment option (due to its low historic utilization in Ontario), MRgHIFU was cost effective with an incremental cost of $39,250 per additional QALY. The budgetary impact of funding MRgHIFU for treatment of symptomatic uterine fibroids was estimated at $1.38 million in savings when funded to replace all types of procedures at 2 centres, and $1.14 million when funded to replace only uterine preserving procedures at 2 centres. The potential savings increase to $4.15 million when MRgHIFU is funded at 6 centres to treat all women eligible for the procedure. Potential savings at 6 centres decrease slightly, to $3.42 million, when MRgHIFU is funded to replace uterine-preserving procedures only. CONCLUSIONS: Our findings suggest that MRgHIFU may be a cost-effective strategy at commonly accepted willingness-to-pay thresholds, after examining the uncertainty in model parameters and several likely scenarios. In terms of budget impact, the implementation of MRgHIFU could potentially result in one-year savings of $1.38 million and $4.15 million in the scenarios where MRgHIFU is implemented in 2 or 6 centres, respectively. From a patient perspective, it is important to consider that MRgHIFU is the least invasive of all fibroid treatment options for women who have not responded to pharmaceuticals; it is the only one that is completely noninvasive. Also important, from a societal point of view, is the potential benefit from faster recovery times. Despite these benefits, implementation of MRgHIFU beyond the 2 centres which currently offer the treatment faces logistical challenges (for example, competing demands for use of existing equipment), as well as financial challenges, with hospitals needing to fundraise to purchase new equipment. PMID- 26357533 TI - Naturally occurring variation in tadpole morphology and performance linked to predator regime. AB - Divergent natural selection drives a considerable amount of the phenotypic and genetic variation observed in natural populations. For example, variation in the predator community can generate conflicting selection on behavioral, life history, morphological, and performance traits. Differences in predator regime can subsequently increase phenotypic and genetic variations in the population and result in the evolution of reproductive barriers (ecological speciation) or phenotypic plasticity. We evaluated morphology and swimming performance in field collected Bronze Frog larvae (Lithobates clamitans) in ponds dominated by predatory fish and those dominated by invertebrate predators. Based on previous experimental findings, we hypothesized that tadpoles from fish-dominated ponds would have small bodies, long tails, and large tail muscles and that these features would facilitate fast-start speed. We also expected to see increased tail fin depth (i.e., the tail-lure morphology) in tadpoles from invertebrate dominated ponds. Our results support our expectations with respect to morphology in affecting swimming performance of tadpoles in fish-dominated ponds. Furthermore, it is likely that divergent natural selection is playing a role in the diversification on morphology and locomotor performance in this system. PMID- 26357530 TI - Magnetic Resonance-Guided High-Intensity Focused Ultrasound (MRgHIFU) Treatment of Symptomatic Uterine Fibroids: An Evidence-Based Analysis. AB - BACKGROUND: Magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU) is a noninvasive uterine-preserving treatment alternative to hysterectomy for women with symptomatic uterine leiomyomas (fibroids). Uterine fibroids commonly occur, have a broad impact on women's health and lifestyle, continue to be the main indication for hysterectomy, and represent a costly public health burden. OBJECTIVES: The objectives of the analysis were to evaluate patients' eligibility for MRgHIFU treatment of symptomatic uterine fibroids and the technical success, safety, effectiveness, and durability of this treatment. The review also compared the safety and effectiveness of MRgHIFU with other minimally invasive uterine preserving treatments and surgeries for uterine fibroids. METHODS: A literature search was performed on March 27, 2014, using Ovid MEDLINE, Ovid MEDLINE In Process and Other Non-Indexed Citations, Ovid EMBASE, EBSCO Cumulative Index to Nursing & Allied Health Literature (CINAHL), and EBM Reviews, for studies published from January 1, 2000, to March 27, 2014. RESULTS: The evidence review identified 2 systematic reviews, 2 RCTs, 45 cohort study reports, and 19 case reports involving HIFU treatment of symptomatic uterine fibroids. Eligibility for MRgHIFU treatment was variable, ranging from 14% to 74%. In clinical cohort studies involving 1,594 patients, 26 major complications (1.6%) were reported. MRgHIFU resulted in statistically and clinically significant reductions in fibroid-related symptoms in studies conducted in 10 countries, although few involved follow-up longer than 1 year. Retreatment rates following MRgHIFU were higher in early clinical studies involving regulated restrictions in the extent of fibroid ablation than in later reports involving near-complete ablation. Emergent interventions, however, were rare. Although a desire for fertility was an exclusion criteria for treatment, spontaneous term pregnancies did occur following HIFU. There were no randomized trials comparing MRgHIFU and other guidance methods, other minimally invasive treatments, or surgeries for symptomatic uterine fibroids. Limitations with MRgHIFU included restricted eligibility, requirement for a dedicated MR device to guide the treatment, lengthy procedure time, and loss of MR opportunity time. CONCLUSIONS: For women failing medical therapy and seeking alternatives to hysterectomy for symptomatic uterine fibroids, MRgHIFU provides a safe and effective, noninvasive, uterine preserving treatment from which they rapidly recover. The treatment advantages of MRgHIFU are potentially offset by restrictive eligibility, lengthy procedure time, and dependence on availability of an MR device. The lack of comparative evidence between MRgHIFU and other, more established uterine-preserving treatments limits informed decision making among treatment options. PMID- 26357534 TI - Hybridization in closely related Rhododendron species: half of all species differentiating markers experience serious transmission ratio distortion. AB - An increasing number of studies of hybridization in recent years have revealed that complete reproductive isolation between species is frequently not finalized in more or less closely related organisms. Most of these species do, however, seem to retain their phenotypical characteristics despite the implication of gene flow, highlighting the remaining gap in our knowledge of how much of an organism's genome is permeable to gene flow, and which factors promote or prevent hybridization. We used AFLP markers to investigate the genetic composition of three populations involving two interfertile Rhododendron species: two sympatric populations, of which only one contained hybrids, and a further hybrid-dominated population. No fixed differences between the species were found, and only 5.8% of the markers showed some degree of species differentiation. Additionally, 45.5% of highly species-differentiating markers experienced significant transmission distortion in the hybrids, which was most pronounced in F1 hybrids, suggesting that factors conveying incompatibilities are still segregating within the species. Furthermore, the two hybrid populations showed stark contrasting composition of hybrids; one was an asymmetrically backcrossing hybrid swarm, while in the other, backcrosses were absent, thus preventing gene flow. PMID- 26357535 TI - Sperm storage and spermatozoa interaction with epithelial cells in oviduct of Chinese soft-shelled turtle, Pelodiscus sinensis. AB - Spermatozoa are known to be stored within the female genital tract after mating in various species to optimize timing of reproductive events such as copulation, fertilization, and ovulation. The mechanism supporting long-term sperm storage is still unclear in turtles. The aim of this study was to investigate the interaction between the spermatozoa and oviduct in Chinese soft-shelled turtle by light and electron microscopy to reveal the potential cytological mechanism of long-term sperm storage. Spermatozoa were stored in isthmus, uterine, and vagina of the oviduct throughout the year, indicating long-term sperm storage in vivo. Sperm heads were always embedded among the cilia and even intercalated into the apical hollowness of the ciliated cells in the oviduct mucosal epithelium. The stored spermatozoa could also gather in the gland conduit. There was no lysosome distribution around the hollowness of the ciliated cell, suggesting that the ciliated cells of the oviduct can support the spermatozoa instead of phagocytosing them in the oviduct. Immune cells were sparse in the epithelium and lamina propria of oviduct, although few were found inside the blood vessel of mucosa, which may be an indication of immune tolerance during sperm storage in the oviduct of the soft-shelled turtle. These characteristics developed in the turtle benefited spermatozoa survival for a long time as extraneous cells in the oviduct of this species. These findings would help to improve the understanding of reproductive regularity and develop strategies of species conservation in the turtle. The Chinese soft-shelled turtle may be a potential model for uncovering the mechanism behind the sperm storage phenomenon. PMID- 26357536 TI - Single nucleotide polymorphism-based dispersal estimates using noninvasive sampling. AB - Quantifying dispersal within wild populations is an important but challenging task. Here we present a method to estimate contemporary, individual-based dispersal distance from noninvasively collected samples using a specialized panel of 96 SNPs (single nucleotide polymorphisms). One main issue in conducting dispersal studies is the requirement for a high sampling resolution at a geographic scale appropriate for capturing the majority of dispersal events. In this study, fecal samples of brown bear (Ursus arctos) were collected by volunteer citizens, resulting in a high sampling resolution spanning over 45,000 km(2) in Gavleborg and Dalarna counties in Sweden. SNP genotypes were obtained for unique individuals sampled (n = 433) and subsequently used to reconstruct pedigrees. A Mantel test for isolation by distance suggests that the sampling scale was appropriate for females but not for males, which are known to disperse long distances. Euclidean distance was estimated between mother and offspring pairs identified through the reconstructed pedigrees. The mean dispersal distance was 12.9 km (SE 3.2) and 33.8 km (SE 6.8) for females and males, respectively. These results were significantly different (Wilcoxon's rank-sum test: P-value = 0.02) and are in agreement with the previously identified pattern of male-biased dispersal. Our results illustrate the potential of using a combination of noninvasively collected samples at high resolution and specialized SNPs for pedigree-based dispersal models. PMID- 26357537 TI - The effect of hydroperiod and predation on the diversity of temporary pond zooplankton communities. AB - In temporary pond ecosystems, it is hypothesized that the two dominant structuring forces on zooplankton communities are predation and demographic constraints due to wetland drying. Both of these forces are deterministic processes that act most strongly at opposing ends of a hydroperiod gradient. Our objective was to test how these two processes affect alpha- and beta-diversity of zooplankton communities derived from a diverse temporary pond system. We hypothesized that decreased hydroperiod length and the presence of salamander larvae as predators would decrease beta-diversity and that intermediate hydroperiod communities would have the greatest species richness. Our 1-year mesocosm experiment (n = 36) consisted of two predation treatments (present/absent) and three hydroperiod treatments (short/medium/long) fully crossed, seeded from the resting egg bank of multiple temporary ponds. In total, we collected 37 species of microcrustacean zooplankton from our mesocosms. A reduction in hydroperiod length resulted in lower alpha-diversity, with short hydroperiod treatments affected most strongly. Endpoint community dissimilarity (beta-diversity) was greatest in the medium-hydroperiod treatment with regard to species presence/absence, but was greatest in the long-hydroperiod treatment when abundances were included. Predation by salamander larvae led to reduced beta diversity with respect to species presence/absence, but not among abundant species, and had no effect on alpha-diversity. Our results suggest that environmental changes that reduce hydroperiod length would result in reduced alpha-diversity; however, intermediate hydroperiod length appear to enhance beta diversity within a group of wetlands. PMID- 26357538 TI - Spatial structuring of the population genetics of a European subterranean termite species. AB - In population genetics studies, detecting and quantifying the distribution of genetic variation can help elucidate ecological and evolutionary processes. In social insects, the distribution of population-level genetic variability is generally linked to colony-level genetic structure. It is thus especially crucial to conduct complementary analyses on such organisms to examine how spatial and social constraints interact to shape patterns of intraspecific diversity. In this study, we sequenced the mitochondrial COII gene for 52 colonies of the subterranean termite Reticulitermes grassei (Isoptera: Rhinotermitidae), sampled from a population in southwestern France. Three haplotypes were detected, one of which was found exclusively in the southern part of the study area (near the Pyrenees). After genotyping 6 microsatellite loci for 512 individual termites, we detected a significant degree of isolation by distance among individuals over the entire range; however, the cline of genetic differentiation was not continuous, suggesting the existence of differentiated populations. A spatial principal component analysis based on allele frequency data revealed significant spatial autocorrelation among genotypes: the northern and southern groups were strongly differentiated. This finding was corroborated by clustering analyses; depending on the randomized data set, two or three clusters, exhibiting significant degrees of differentiation, were identified. An examination of colony breeding systems showed that colonies containing related neotenic reproductives were prevalent, suggesting that inbreeding may contribute to the high level of homozygosity observed and thus enhance genetic contrasts among colonies. We discuss the effect of evolutionary and environmental factors as well as reproductive and dispersal modes on population genetic structure. PMID- 26357539 TI - Toxicity and utilization of chemical weapons: does toxicity and venom utilization contribute to the formation of species communities? AB - Toxicity and the utilization of venom are essential features in the ecology of many animal species and have been hypothesized to be important factors contributing to the assembly of communities through competitive interactions. Ants of the genus Monomorium utilize a variety of venom compositions, which have been reported to give them a competitive advantage. Here, we investigate two pairs of Monomorium species, which differ in the structural compositions of their venom and their co-occurrence patterns with the invasive Argentine ant. We looked at the effects of Monomorium venom toxicity, venom utilization, and aggressive physical interactions on Monomorium and Argentine ant survival rates during arena trials. The venom toxicity of the two species co-occurring with the invasive Argentine ants was found to be significantly higher than the toxicity of the two species which do not. There was no correlation between venom toxicity and Monomorium survival; however, three of the four Monomorium species displayed significant variability in their venom usage which was associated with the number of Argentine ant workers encountered during trials. Average Monomorium mortality varied significantly between species, and in Monomorium smithii and Monomorium antipodum, aggressive interactions with Argentine ants had a significant negative effect on their mortality. Our study demonstrates that different factors and strategies can contribute to the ability of a species to withstand the pressure of a dominant invader at high abundance, and venom chemistry appears to be only one of several strategies utilized. PMID- 26357540 TI - Morphological divergence between three Arctic charr morphs - the significance of the deep-water environment. AB - Morphological divergence was evident among three sympatric morphs of Arctic charr (Salvelinus alpinus (L.)) that are ecologically diverged along the shallow-, deep water resource axis in a subarctic postglacial lake (Norway). The two deep-water (profundal) spawning morphs, a benthivore (PB-morph) and a piscivore (PP-morph), have evolved under identical abiotic conditions with constant low light and temperature levels in their deep-water habitat, and were morphologically most similar. However, they differed in important head traits (e.g., eye and mouth size) related to their different diet specializations. The small-sized PB-morph had a paedomorphic appearance with a blunt head shape, large eyes, and a deep body shape adapted to their profundal lifestyle feeding on submerged benthos from soft, deep-water sediments. The PP-morph had a robust head, large mouth with numerous teeth, and an elongated body shape strongly related to their piscivorous behavior. The littoral spawning omnivore morph (LO-morph) predominantly utilizes the shallow benthic-pelagic habitat and food resources. Compared to the deep water morphs, the LO-morph had smaller head relative to body size. The LO-morph exhibited traits typical for both shallow-water benthic feeding (e.g., large body depths and small eyes) and planktivorous feeding in the pelagic habitat (e.g., streamlined body shape and small mouth). The development of morphological differences within the same deep-water habitat for the PB- and PP-morphs highlights the potential of biotic factors and ecological interactions to promote further divergence in the evolution of polymorphism in a tentative incipient speciation process. The diversity of deep-water charr in this study represents a novelty in the Arctic charr polymorphism as a truly deep-water piscivore morph has to our knowledge not been described elsewhere. PMID- 26357541 TI - Tetracycline-exposed Drosophila melanogaster males produce fewer offspring but a relative excess of sons. AB - A large diversity of species possesses endosymbionts; these endosymbionts can exhibit mutualistic, parasitic, and commensal relationships with their hosts. Previous work has consistently revealed that depleting endosymbiont titer with antibiotic treatment can significantly alter host fitness and function, particularly with respect to reproductive phenotypes. Although these findings are often interpreted as resulting from the breakdown of highly coevolved symbioses, it is possible that antibiotic treatment itself rather than endosymbiont removal contributes to the observed perturbations in reproductive phenotypes. Here, we investigate the effect of tetracycline treatment on sex ratio and male reproductive fitness using Drosophila melanogaster as a model system. Our results indicate that tetracycline-treated males produce a relative excess of sons. We also find that tetracycline treatment reduces the number of progeny produced by treated males but not treated females. These findings are independent of the effects of tetracycline on Wolbachia titer and implicate the antibiotic itself as mediating these changes. It is yet unclear whether the sex ratio shift and reduction in male reproductive fitness are direct or indirect consequences of tetracycline exposure, and more work is needed to determine the molecular mechanisms by which these disturbances in reproductive phenotypes arise. Our data highlight the importance of considering the potentially confounding effects of antibiotic treatment when investigating the effects of endosymbiont depletion on host phenotypes. PMID- 26357542 TI - The use and abuse of genetic marker-based estimates of relatedness and inbreeding. AB - Genetic marker-based estimators remain a popular tool for measuring relatedness (r xy ) and inbreeding (F) coefficients at both the population and individual level. The performance of these estimators fluctuates with the number and variability of markers available, and the relatedness composition and demographic history of a population. Several methods are available to evaluate the reliability of the estimates of r xy and F, some of which are implemented in the program COANCESTRY. I used the simulation module in COANCESTRY since assess the performance of marker-based estimators of r xy and F in a species with very low genetic diversity, New Zealand's little spotted kiwi (Apteryx owenii). I also conducted a review of published papers that have used COANCESTRY as its release to assess whether and how the reliability of the estimates of r xy and F produced by genetic markers are being measured and reported in published studies. My simulation results show that even when the correlation between true (simulated) and estimated r xy or F is relatively high (Pearson's r = 0.66-0.72 and 0.81 0.85, respectively) the imprecision of the estimates renders them highly unreliable on an individual basis. The literature review demonstrates that the majority of studies do not report the reliability of marker-based estimates of r xy and F. There is currently no standard practice for selecting the best estimator for a given data set or reporting an estimator's performance. This could lead to experimental results being interpreted out of context and render the robustness of conclusions based on measures of r xy and F debatable. PMID- 26357543 TI - Postmating reproductive barriers contribute to the incipient sexual isolation of the United States and Caribbean Drosophila melanogaster. AB - The nascent stages of speciation start with the emergence of sexual isolation. Understanding the influence of reproductive barriers in this evolutionary process is an ongoing effort. We present a study of Drosophila melanogaster admixed populations from the southeast United States and the Caribbean islands known to be a secondary contact zone of European- and African-derived populations undergoing incipient sexual isolation. The existence of premating reproductive barriers has been previously established, but these types of barriers are not the only source shaping sexual isolation. To assess the influence of postmating barriers, we investigated putative postmating barriers of female remating and egg laying behavior, as well as hatchability of eggs laid and female longevity after mating. In the central region of our putative hybrid zone of American and Caribbean populations, we observed lower hatchability of eggs laid accompanied by increased resistance to harm after mating to less-related males. These results illustrate that postmating reproductive barriers act alongside premating barriers and genetic admixture such as hybrid incompatibilities and influence early phases of sexual isolation. PMID- 26357544 TI - Adaptive plasticity and niche expansion in an invasive thistle. AB - Phenotypic differentiation in size and fecundity between native and invasive populations of a species has been suggested as a causal driver of invasion in plants. Local adaptation to novel environmental conditions through a micro evolutionary response to natural selection may lead to phenotypic differentiation and fitness advantages in the invaded range. Local adaptation may occur along a stress tolerance trade-off, favoring individuals that, in benign conditions, shift resource allocation from stress tolerance to increased vigor and fecundity and, therefore, invasiveness. Alternately, the typically disturbed invaded range may select for a plastic, generalist strategy, making phenotypic plasticity the main driver of invasion success. To distinguish between these hypotheses, we performed a field common garden and tested for genetically based phenotypic differentiation, resource allocation shifts in response to water limitation, and local adaptation to the environmental gradient which describes the source locations for native and invasive populations of diffuse knapweed (Centaurea diffusa). Plants were grown in an experimental field in France (naturalized range) under water addition and limitation conditions. After accounting for phenotypic variation arising from environmental differences among collection locations, we found evidence of genetic variation between the invasive and native populations for most morphological and life-history traits under study. Invasive C. diffusa populations produced larger, later maturing, and therefore potentially fitter individuals than native populations. Evidence for local adaptation along a resource allocation trade-off for water limitation tolerance is equivocal. However, native populations do show evidence of local adaptation to an environmental gradient, a relationship which is typically not observed in the invaded range. Broader analysis of the climatic niche inhabited by the species in both ranges suggests that the physiological tolerances of C. diffusa may have expanded in the invaded range. This observation could be due to selection for plastic, "general-purpose" genotypes with broad environmental tolerances. PMID- 26357546 TI - Outcomes following repair of anomalous coronary artery from the pulmonary artery in infants: results from a procedure-based national database. AB - BACKGROUND: Anomalous coronary artery from the pulmonary artery (ACAPA) is a very rare congenital anomaly that often occurs during infancy. Patients can present in a critical condition. METHODS: We analysed procedure-related data from a national audit database for the period 2000-2013. RESULTS: A total of 120 patients <1 year had repair of isolated ACAPA using a coronary transfer or the tunnel (Takeuchi) operation. Seven patients (6.8%) required a mitral valve procedure at index and eight patients (7.8%) had a mitral valve repair/replacement during follow-up, including mitral reoperations. Follow-up data (>30 days) were available in 102 patients and the mean follow-up time was 4.7 years. The 30-day overall mortality was 1.9%, higher for neonates (16.7% vs 1%, p=0.1) and after postoperative extracorporeal membrane oxygenation (ECMO) (20% vs 1%, p=0.09). At 10 years the survival estimate is 95.1%, freedom from coronary and mitral reintervention being 95.9% and 91.2%, respectively. Use of postoperative ECMO was a risk factor for long-term mortality (p<0.001). Risk factors for coronary reintervention were age under 30 days (p=0.06) and the need for postoperative ECMO (p=0.02). Age under 30 days (p=0.002) was a risk factor for mitral reintervention. CONCLUSIONS: To our knowledge this is the largest series to date. These preliminary national results show that early outcomes are good and medium-term attrition acceptable. Poor outcomes are correlated with early presentation, also with the need for postoperative circulatory support. PMID- 26357547 TI - Dramatic resolution of vitreous hemorrhage after an intravitreal injection of dobesilate. AB - Vitreous hemorrhages are important clinical manifestations of proliferative diabetic retinopathy. Non-cleared vitreous hemorrhages could lead to hemosiderosis bulbi and glaucoma. Here, we describe the case of a type 2 diabetic patient presenting anterior segment and vitreous hemorrhages that resolved three days after treatment with a single intravitreal injection of dobesilate. PMID- 26357548 TI - Diagnostic Factors of Odontogenic Cysts in Iranian Population: A Retrospective Study Over the Past Two Decades. AB - BACKGROUND: Early diagnosis of odontogenic cysts due to their silent progression is always a challenging problem for clinicians. OBJECTIVES: The current study aimed to evaluate the frequency of odontogenic cysts and related factors in a selected Iranian population. PATIENTS AND METHODS: The current cross-sectional study was conducted on 312 patients' recorded data in Taleghani Hospital, Tehran, Iran, from April 1993 to December 2013. All related data were extracted from the records and categorized in tables. The correlation between the variables was analyzed by either chi-square or multinominal logistic regression tests. The P values < 0.05 were considered significant. RESULTS: Evaluation of 312 patients' records (185 males and 127 females) with the mean age of 27.6 showed that Odontogenic Keratocyst (OKC) was the most common odontogenic cyst of all followed by the dentigerous cyst as the second most common lesion. Most of the patients were in the second or third decades of their lives, although there was no statistically significant age distribution. The finding of the current study showed that calcifying odontogenic cyst (COC) occurrence was significantly related to the history of trauma. Enucleation and curettage of the odontogenic cysts were the most common treatment plans of all. CONCLUSIONS: The current study showed that clinicians should consider the many factors associated with the occurrence of odontogenic cysts. PMID- 26357549 TI - Preventing the Future Pandemic of Diabetes Mellitus in Oman. PMID- 26357551 TI - A Call for More Diploma Nurses to Attain a Baccalaureate Degree: Advancing the nursing profession in Oman. AB - The healthcare needs of the Omani population are evolving, particularly with regards to changes in disease complexity, advances in technology and the enhanced delivery of healthcare services. Nurses now need to adapt to a fundamental shift in the provision of patient-centred care. In line with lifelong learning goals, registered nurses in Oman at the diploma level should seek to obtain a more advanced qualification, for instance a Bachelor of Science in Nursing, to ensure they possess the requisite skills and knowledge to keep abreast of new developments in healthcare management. Challenges involved in this transition and suggestions to overcome these potential obstacles are discussed in this article in order to inform nursing education stakeholders. Recommendations to ensure the success of bridging programmes are also suggested. PMID- 26357550 TI - The Role of Inflammatory Mediators in the Pathogenesis of Alzheimer's Disease. AB - Alzheimer's disease (AD), a neurodegenerative disorder associated with advanced age, is the most common cause of dementia globally. AD is characterised by cognitive dysfunction, deposition of amyloid plaques, neurofibrillary tangles and neuro-inflammation. Inflammation of the brain is a key pathological hallmark of AD. Thus, clinical and immunopathological evidence of AD could be potentially supported by inflammatory mediators, including cytokines, chemokines, the complement system, acute phase proteins and oxidative mediators. In particular, oxidative mediators may actively contribute to the progression of AD and on-going inflammation in the brain. This review provides an overview of the functions and activities of inflammatory mediators in AD. An improved understanding of inflammatory processes and their role in AD is needed to improve therapeutic research aims in the field of AD and similar diseases. PMID- 26357552 TI - Skeletal Muscle Metastasis from Renal Cell Carcinoma: 21 cases and review of the literature. AB - OBJECTIVES: This study aimed to raise radiologists' awareness of skeletal muscle metastases (SMM) in renal cell carcinoma (RCC) cases and to clarify their imaging appearance. METHODS: A retrospective analysis was undertaken of 21 patients between 44-75 years old with 72 SMM treated from January 1990 to May 2009 at the MD Anderson Cancer Center in Houston, Texas, USA. Additionally, 37 patients with 44 SMM from a literature review were analysed. RESULTS: Among the 21 patients, the majority of SMM were asymptomatic and detected via computed tomography (CT). Mean metastasis size was 18.3 mm and the most common site was the trunk muscles (83.3%). The interval between discovery of the primary tumour and metastasis detection ranged up to 234 months. Peripheral enhancement (47.1%) was the most common post-contrast CT pattern and non-contrasted CT lesions were often isodense. Magnetic resonance imaging (MRI) characteristics were varied. Five lesions with available T1-weighted pre-contrast images were hyperintense to the surrounding muscle. Other organ metastases were present in 20 patients. Of the 44 SMM reported in the literature, the majority were symptomatic. Average metastasis size was 53.4 mm and only 20.5% of SMM were in trunk muscles. The average interval between tumour discovery and metastasis detection was 101 months. Other organ metastases were recorded in 17 out of 29 patients. CONCLUSION: SMM should always be considered in patients with RCC, even well after primary treatment. SMM from RCC may be invisible on CT without intravenous contrast; contrast-enhanced studies are therefore recommended. SMM are often hyperintense to the surrounding muscle on T1-weighted MRI scans. PMID- 26357553 TI - Gallium-67 Scintigraphy in the Era of Positron Emission Tomography and Computed Tomography: Tertiary centre experience. AB - OBJECTIVES: Although (18)F-fluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT) has largely replaced the use of gallium-67 ((67)Ga) scintigraphy in the evaluation and follow-up of lymphoma patients, (67)Ga scans are still of value, particularly in countries where no PET/CT service is available. The current study presents the experience of a tertiary care centre using (67)Ga scintigraphy for the evaluation of lymphomas and infections. METHODS: A retrospective review was conducted of all (67)Ga scans performed between 2007 and 2011 at the Royal Hospital in Muscat, Oman. Images and reports of (67)Ga scans were compared to clinical and radiological follow-up data including CT and PET/CT scans and biopsies when available. RESULTS: A total of 74 patients were referred for (67)Ga scintigraphy during this period with 12 patients excluded due to lack of follow-up data, resulting in 62 patients. Among these patients, 90 (67)Ga scans were performed, including 59 for lymphoma, 29 for infection and two for sarcoidosis assessment. Of the infection assessment scans, 22 were performed to assess pyrexia of unknown origin and seven for follow-up after known infections. Sensitivity and specificity were found to be 80% and 88%, respectively, for the lymphoma assessment scans. For the infection assessment scans, sensitivity and specificity were reported to be 80% and 100%, respectively. CONCLUSION: Results from this study were consistent with other reported rates of (67)Ga scan sensitivity and specificity in the evaluation of lymphomas and infections. This indicates that (67)Ga scintigraphy is a useful tool for these types of evaluations when PET/CT services are not available. PMID- 26357554 TI - Correlation between Carotid Artery Intima-Media Thickness and Luminal Diameter with Body Mass Index and Other Cardiovascular Risk Factors in Adults. AB - OBJECTIVES: This study aimed to examine the correlation between carotid artery intima-media thickness (IMT) and luminal diameter (LD) with body mass index (BMI) and other cardiovascular risk factors. METHODS: This observational cross sectional study took place between June 2013 and March 2014 in the Radiology Department of Rizgary Teaching Hospital in Erbil, Iraq. Non-randomly selected subjects >=20 years old (n = 140) were divided into BMI groups and evaluated for the following cardiovascular risk factors: gender, age, hypertension (HTN), diabetes (DM), smoking, alcohol consumption, blood pressure, serum total cholesterol and triglyceride (TG) levels. IMT and LD of the extracranial carotid arteries were measured by B-mode ultrasonography. RESULTS: The mean IMT was 0.8 +/- 0.3 mm, ranging from a total mean of 0.7 mm in the normal BMI group to 1.0 mm in the extremely obese group. A significant correlation was found between IMT and BMI (P = 0.04), but not between BMI and LD (P = 0.3). No significant difference in mean IMT or LD was seen between genders. Significant correlations were found between IMT and age, HTN, DM, high serum cholesterol and TG levels (P <0.001). An increase of one BMI unit caused a 0.009 mm increase in IMT and an increase of one year in age caused a 0.011 mm increase in IMT. CONCLUSION: Age, obesity, HTN, DM, high serum cholesterol and TG levels were found to have an impact on carotid IMT, which is a strong marker for the early development of atherosclerosis. PMID- 26357555 TI - Changing Survival Rate of Infants Born Before 26 Gestational Weeks: Single-centre study. AB - OBJECTIVES: This study aimed to evaluate the changing survival rate and morbidities among infants born before 26 gestational weeks at the Sultan Qaboos University Hospital (SQUH) in Muscat, Oman. METHODS: This retrospective study assessed the mortality and morbidities of all premature infants born alive at 23 26 gestational weeks at SQUH between June 2006 and May 2013. Infants referred to SQUH within 72 hours of birth during this period were also included. Electronic records were reviewed for gestational age, gender, birth weight, maternal age, mode and place of delivery, antenatal steroid administration, morbidity and outcome. The survival rate was calculated and findings were then compared with those of a previous study conducted in the same hospital from 1991 to 1998. Rates of major morbidities were also calculated. RESULTS: A total of 81 infants between 23-26 gestational weeks were admitted to the neonatal unit during the study period. Of these, 58.0% were male and 42.0% were female. Median gestational age was 25 weeks and mean birth weight was 770 +/- 150 g. Of the 81 infants, 49 survived. The overall survival rate was 60.5% compared to 41% reported in the previous study. Respiratory distress syndrome (100.0%), retinopathy of prematurity (51.9%), bronchopulmonary dysplasia (34.6%), intraventricular haemorrhage (30.9%) and patent ductus arteriosus (28.4%) were the most common morbidities. CONCLUSION: The overall survival rate of infants between 23-26 gestational weeks during the study period had significantly improved in comparison to that found at the same hospital from 1991 to 1998. There is a need for the long-term neurodevelopmental follow-up of premature infants. PMID- 26357556 TI - Social Networking Addiction among Health Sciences Students in Oman. AB - OBJECTIVES: Addiction to social networking sites (SNSs) is an international issue with numerous methods of measurement. The impact of such addictions among health science students is of particular concern. This study aimed to measure SNS addiction rates among health sciences students at Sultan Qaboos University (SQU) in Muscat, Oman. METHODS: In April 2014, an anonymous English-language six-item electronic self-reporting survey based on the Bergen Facebook Addiction Scale was administered to a non-random cohort of 141 medical and laboratory science students at SQU. The survey was used to measure usage of three SNSs: Facebook (Facebook Inc., Menlo Park, California, USA), YouTube (YouTube, San Bruno, California, USA) and Twitter (Twitter Inc., San Francisco, California, USA). Two sets of criteria were used to calculate addiction rates (a score of 3 on at least four survey items or a score of 3 on all six items). Work-related SNS usage was also measured. RESULTS: A total of 81 students completed the survey (response rate: 57.4%). Of the three SNSs, YouTube was most commonly used (100%), followed by Facebook (91.4%) and Twitter (70.4%). Usage and addiction rates varied significantly across the three SNSs. Addiction rates to Facebook, YouTube and Twitter, respectively, varied according to the criteria used (14.2%, 47.2% and 33.3% versus 6.3%, 13.8% and 12.8%). However, addiction rates decreased when work related activity was taken into account. CONCLUSION: Rates of SNS addiction among this cohort indicate a need for intervention. Additionally, the results suggest that addiction to individual SNSs should be measured and that work-related activities should be taken into account during measurement. PMID- 26357557 TI - Rigid Spine Syndrome among Children in Oman. AB - OBJECTIVES: Rigidity of the spine is common in adults but is rarely observed in children. The aim of this study was to report on rigid spine syndrome (RSS) among children in Oman. METHODS: Data on children diagnosed with RSS were collected consecutively at presentation between 1996 and 2014 at the Sultan Qaboos University Hospital (SQUH) in Muscat, Oman. A diagnosis of RSS was based on the patient's history, clinical examination, biochemical investigations, electrophysiological findings, neuro-imaging and muscle biopsy. Atrophy of the paraspinal muscles, particularly the erector spinae, was the diagnostic feature; this was noted using magnetic resonance imaging of the spine. Children with disease onset in the paraspinal muscles were labelled as having primary RSS or rigid spinal muscular dystrophy. Secondary RSS was classified as RSS due to the late involvement of other muscle diseases. RESULTS: Over the 18-year period, 12 children were included in the study, with a male-to-female ratio of 9:3. A total of 10 children were found to have primary RSS or rigid spinal muscular dystrophy syndrome while two had secondary RSS. Onset of the disease ranged from birth to 18 months of age. A family history was noted, with two siblings from one family and three siblings from another (n = 5). On examination, children with primary RSS had typical features of severe spine rigidity at onset, with the rest of the neurological examination being normal. CONCLUSION: RSS is a rare disease with only 12 reported cases found at SQUH during the study period. Cases of primary RSS should be differentiated from the secondary type. PMID- 26357558 TI - Shigellosis Outbreak in Al Batinah South Governorate, Oman: Case-control study. AB - OBJECTIVES: An outbreak of acute gastroenteritis due to Shigella flexneri occurred in August 2012 in the catchment area of the Wadi Sahtan Health Center in Rustaq, Al Batinah South Governorate, Oman. The aim of this study was to discover possible causes of this outbreak in the villages of Fassa, Rogh and Amk and to measure the risk of exposure among cases and controls. METHODS: A case-control study was conducted in September 2012 in Fassa, Rogh and Amk. All households in the three villages were interviewed. Case and control households were compared to determine possible exposure avenues, including place of residence, source of drinking water, hand hygiene levels and practices related to drinking water, food preparation and environmental sanitation. RESULTS: Residing in Fassa (P <0.0001; odds ratio [OR] = 4.86, 95% confidence interval [CI] = 2.22-10.63) and average hand hygiene practices (P = 0.008; OR = 13.97, 95% CI = 1.58-123.36) were associated with an increased risk of contracting shigellosis. No significant differences were found with regards to the other exposure avenues. CONCLUSION: This was the first study conducted in Oman regarding an outbreak of shigellosis in a community setting. The only variables that significantly impacted the risk of acute gastroenteritis were residing in Fassa and average hand hygiene practices. The source of the outbreak could not be identified. However, septic tank sanitation and water and food consumption practices were not satisfactory in the studied villages. These need to be addressed to prevent similar outbreaks of acute gastroenteritis in this region in the future. PMID- 26357559 TI - Risky Driving Behaviours among Medical Students in Erbil, Iraq. AB - OBJECTIVES: This study aimed to assess risky driving behaviours among medical students in Erbil, Iraq, and to explore the relationship between risky driving behaviours and perceptions of risky driving. METHODS: This self-administered questionnaire-based survey was conducted from January to May 2014 among a random sample of 400 medical students at Hawler Medical University in Erbil. The questionnaire was designed to assess the frequency of engagement in 21 risky driving behaviours, the perceived risk of each behaviour and the preference for each behaviour as ranked on a 5-point scale. RESULTS: A total of 386 students responded to the survey (response rate: 96.5%). Of these, 211 reported that they currently drove a vehicle (54.7%). Drivers most frequently engaged in the following behaviours: playing loud music (35.9%), speeding (30.4%), allowing front seat passengers to not wear seat belts (27.9%) and using mobile phones (27.7%). Least frequent driving behaviours included not stopping at a red light (3.9%), driving while sleepy (4.4%), driving after a mild to moderate intake of alcohol (4.5%) and drunk driving (6.4%). Mean risky driving behaviour scores were significantly higher among males (P <0.001) and those who owned a car (P = 0.002). The mean risk perception score was higher among >20-year-olds (P = 0.028). There was a significant positive relationship between the preference for risky behaviours and risky driving behaviours (beta = 0.44; P <0.001). CONCLUSION: Medical students in Erbil reported high frequencies of several serious risky driving behaviours. The preference for risky behaviours was found to be an important predictor of risky driving behaviours among medical students in Erbil. PMID- 26357560 TI - De Novo Duplication of 7p21.1p22.2 in a Child with Autism Spectrum Disorder and Craniofacial Dysmorphism. AB - The duplication of the short arm of chromosome 7 as de novo is extremely rare. The phenotype spectrum varies depending on the region of duplication. We report a case of de novo duplication of chromosomal region 7p21.1p22.2 in a three-year-old male child with autism who presented to the Sultan Qaboos University Hospital in Muscat, Oman, in January 2012. The patient was diagnosed with craniofacial dysmorphism, global developmental delay, hypotonia and bilateral cryptorchidism. The duplication was detected by conventional G-banded karyotype analysis/fluorescence in situ hybridisation and confirmed by array comparative genomic hybridisation. To the best of the authors' knowledge, this is the first report of chromosomal region 7p21.1 involvement in an autistic patient showing features of a 7p duplication phenotype. Identifying genes in the duplicated region using molecular techniques is recommended to promote characterisation of the phenotype and associated condition. It may also reveal the possible role of these genes in autism spectrum disorder. PMID- 26357561 TI - Localised Skin Hyperpigmentation as a Presenting Symptom of Vitamin B12 Deficiency Complicating Chronic Atrophic Gastritis. AB - Vitamin B12 deficiency is common in developing countries and should be suspected in patients with unexplained anaemia or neurological symptoms. Dermatological manifestations associated with this deficiency include skin hyper- or hypopigmentation, angular stomatitis and hair changes. We report a case of a 28 year-old man who presented to the Sultan Qaboos University Hospital in Muscat, Oman, in November 2013 with localised hyperpigmentation of the palmar and dorsal aspects of both hands of two months' duration. Other symptoms included numbness of the hands, anorexia, weight loss, dizziness, fatigability and a sore mouth and tongue. There was no evidence of hypocortisolaemia and a literature search revealed a possible B12 deficiency. The patient had low serum B12 levels and megaloblastic anaemia. An intrinsic factor antibody test was negative. A gastric biopsy revealed chronic gastritis. After B12 supplementation, the patient's symptoms resolved. Family physicians should familiarise themselves with atypical presentations of B12 deficiency. Many symptoms of this deficiency are reversible if detected and treated early. PMID- 26357562 TI - Posterior Reversible Encephalopathy Syndrome in Two Omani Children with Underlying Renal Diseases. AB - Posterior reversible encephalopathy syndrome (PRES) is a neurological condition with a combination of clinical and radiological features. Clinical symptoms include headaches, confusion, seizures, disturbed vision or an altered level of consciousness. Classic magnetic resonance imaging (MRI) findings indicate subcortical and cortical oedema, affecting mainly the posterior cerebral region. We report two paediatric cases of PRES with underlying renal diseases presenting at the Sultan Qaboos University Hospital in Muscat, Oman, in April 2010 and August 2011. The first case was an 11-year-old girl diagnosed with systemic lupus erythematosus and the second was a six-and-a-half-year-old boy on peritoneal dialysis due to multi-drug-resistant nephrotic syndrome. Both patients were hypertensive and treated with blood pressure control medications. No residual neurological dysfunction was noted in the patients at a one-year follow-up and at discharge, respectively. The role of hypertension in paediatric PRES cases, among other important risk factors, is emphasised. Additionally, MRI is an important diagnostic and prognostic tool. Prompt diagnosis and aggressive management is fundamental to preventing permanent neurological damage. PMID- 26357563 TI - Ruptured Rudimentary Horn Pregnancy Diagnosed by Preoperative Magnetic Resonance Imaging Resulting in Fetal Salvage. AB - Pregnancy in a rudimentary horn is very rare. The rupture of the horn during pregnancy is an obstetric emergency which can be life-threatening for both the mother and fetus. Preoperative diagnosis of such pregnancies can be challenging and they are usually diagnosed intraoperatively. We report a unique case of a 31 year-old multiparous woman who presented to the Sultan Qaboos University Hospital in Muscat, Oman, in January 2013 at 32 gestational weeks with abdominal pain. Ultrasonography was inconclusive. A rudimentary horn pregnancy was subsequently diagnosed via magnetic resonance imaging (MRI). An emergency laparotomy revealed haemoperitoneum and a ruptured rudimentary horn pregnancy. A live baby with an Apgar score of 2 at one minute and 7 at five minutes was delivered. The rudimentary horn with the placenta in situ was excised and a left salpingo oophorectomy was performed. The postoperative period was uneventful. The authors recommend MRI as an excellent diagnostic modality to confirm rudimentary horn pregnancies and to expedite appropriate management. PMID- 26357565 TI - Anterior Inferior Cerebellar Artery Loop-Induced Paroxysmal Otalgia in a Child. PMID- 26357564 TI - Botryoid Rhabdomyosarcoma of the Cervix: Case report with review of the literature. AB - Botryoid rhabdomyosarcoma is an aggressive malignancy that arises from embryonal rhabdomyoblasts. It is commonly seen in the genital tract of female infants and young children. Due to the young age of affected patients, this malignancy poses a management challenge as the preservation of hormonal, sexual and reproductive function is essential. There is currently no consensus regarding management. However, treatment strategies for these tumours have evolved from radical exenterative surgeries to more conservative management options. We report a case of botryoid rhabdomyosarcoma in an adolescent girl presenting to Kasturba Hospital, in Manipal, India, in August 2007 with botryoid rhabdomyosarcoma of the cervix. She was treated with surgery and adjuvant chemotherapy. The patient remained healthy until eight months after the surgery. After acquiring a varicella zoster virus infection, she died due to septic shock and multiple organ failure. Awareness of such an uncommon lesion and its clinical implications is important to avoid misdiagnosis. PMID- 26357566 TI - Congenital Lingual Melanotic Macule: Rare entity in infants. PMID- 26357567 TI - Re: Sodium Valproate-Induced Myopathy in a Child. PMID- 26357568 TI - Efficacy of Once Daily Darunavir/Ritonavir in PI-Naive, NNRTI-Experienced Patients in the ODIN Trial. AB - Background. An exploratory subanalysis of the ODIN trial was performed to evaluate the efficacy of darunavir/ritonavir (DRV/r) 800/100 mg OD versus 600/100 mg BID in patients who were NNRTI-experienced but PI-naive. Methods. ODIN was a phase III, 48-week study comparing DRV/r OD versus BID in 590 treatment experienced patients with no DRV resistance-associated mutations (RAMs) at screening. Patients received DRV/r 800/100 mg OD or DRV/r 600/100 mg BID plus >=2 NRTIs. Of the 590 patients randomized, 272 (46%) were NNRTI-experienced but PI naive. Results. Overall, 272 patients received DRV/r OD (n = 135) or BID (n = 137) plus >=2 optimised NRTIs. The mean age was 39 years; 35% were female; 27% were Black, 24% Caucasian, 26% Oriental/Asian, and 23% other races; 17% were recruited in South Africa; and 48% had non-B HIV-1 subtypes. Mean baseline plasma HIV-1 RNA load was 4.10 log10? copies/mL; median CD4 cell count was 258 cells/MUL. At week 48, 111/135 (82%) of DRV/r OD and 109/137 (80%) of DRV/r BID patients achieved an HIV-1 RNA load <50 copies/mL. No patient developed primary PI RAMs. Conclusion. DRV/r 800/100 mg OD in combination with >=2 optimised NRTIs led to virological suppression <50 copies/mL in 82% of NNRTI-experienced, PI naive patients by week 48. PMID- 26357569 TI - Increasing Understanding in Children of Depressed Parents: Predictors and Moderators of Intervention Response. AB - We evaluated predictors and moderators of differential response to two family based depression prevention programs for families with a depressed parent: a clinician-facilitated intervention and a lecture group intervention. Individual and family level variables were examined using regression analyses with generalized estimating equations. For the outcome of child understanding of depression, parental changes in child-related behaviors and attitudes predicted greater child understanding (p < 0.001). For the parent outcome of behavior and attitude change, across intervention conditions, younger parent age (p < 0.05), female parent gender (p < 0.01), more chronic and severe parental depression history (p < 0.05), lower SES (p < 0.05), and single-parent status (p < 0.05) were associated with better outcomes across conditions. Effect sizes were moderate, ranging from 0.4 to 0.7 SD. Family and marital functioning were not found to be predictors of any outcomes. When both parents were depressed at baseline, there was no difference in the clinician- versus lecture-based approach, and when only the father was depressed, families reported more changes with the clinician condition than with the lecture condition (p < 0.05). Findings from this study can help identify intervention strategies that are appropriate for different types of at-risk individuals and families. PMID- 26357570 TI - Retrograde Intrarenal Surgery in Patients Who Previously Underwent Open Renal Stone Surgery. AB - Purpose. To ascertain whether retrograde intrarenal surgery (RIRS) is as effective in patients treated previously with open renal stone surgery (ORSS) on the same kidney as in patients with no previous ORSS. Methods. There were 32 patients with renal stones who had previous ORSS and were treated with RIRS in the study group (Group 1). A total of 38 patients with renal stones who had no previous ORSS and were treated with RIRS were selected as the control group (Group 2). Recorded data regarding preoperative characteristics of the patients, stone properties, surgical parameters, outcomes, SFRs (no fragments or small fragments <4 mm), and complications between groups were compared. Results. Mean age, mean BMI, mean hospital stay, and mean operative time were not statistically different between groups. Mean stone size (10.1 +/- 5.6 versus 10.3 +/- 4.2; p = 0.551) and mean stone burden (25.4 +/- 14.7 versus 23.5 +/- 9.9; p = 0.504) were also similar between groups. After the second procedures, SFRs were 100% and 95% in groups 1 and 2, respectively (p = 0.496). No major perioperative complications were seen. Conclusion. RIRS can be safely and effectively performed with acceptable complication rates in patients treated previously with ORSS as in patients with no previous ORSS. PMID- 26357571 TI - Role of Health Literacy in Self-Reported Musculoskeletal Disorders. AB - Self-report of musculoskeletal conditions is often used to estimate population prevalence and to determine disease burden and influence policy. However, self report of certain musculoskeletal conditions is frequently inaccurate, suggesting inadequate communication to the patient of their diagnosis. The aim of this study is to determine the association between functional health literacy (FHL) and self reported musculoskeletal conditions in a representative population survey. FHL was measured using Newest Vital Sign in 2824 randomly selected adults. Participants also self-reported medically diagnosed arthritis, gout, and osteoporosis. Multiple logistic regression was adjusted for age and sex. The prevalence of self-reported arthritis, gout, and osteoporosis was 25.2%, 4.9%, and 5.6%, respectively. The prevalence of those at risk for inadequate FHL was 24.0% and high likelihood of inadequate FHL was 21.0%. However, over 50% of respondents with arthritis or gout had at risk/inadequate FHL, increasing to 70% of those self-reporting osteoporosis. After adjustment for age and sex, respondents in the arthritis subgroup of "don't know" and self-reported osteoporosis were significantly more likely to have inadequate FHL than the general population. This study indicates a substantial burden of low health literacy amongst people with musculoskeletal disease. This has implications for provider-patient communication, individual healthcare, population estimates of musculoskeletal disease, and impact of public health messages. PMID- 26357572 TI - Systems Medicine: The Application of Systems Biology Approaches for Modern Medical Research and Drug Development. AB - The exponential development of highly advanced scientific and medical research technologies throughout the past 30 years has arrived to the point where the high number of characterized molecular agents related to pathogenesis cannot be readily integrated or processed by conventional analytical approaches. Indeed, the realization that several moieties are signatures of disease has partly led to the increment of complex diseases being characterized. Scientists and clinicians can now investigate and analyse any individual dysregulations occurring within the genomic, transcriptomic, miRnomic, proteomic, and metabolomic levels thanks to currently available advanced technologies. However, there are drawbacks within this scientific brave new age in that only isolated molecular levels are individually investigated for their influence in affecting any particular health condition. Since their conception in 1992, systems biology/medicine focuses mainly on the perturbations of overall pathway kinetics for the consequent onset and/or deterioration of the investigated condition/s. Systems medicine approaches can therefore be employed for shedding light in multiple research scenarios, ultimately leading to the practical result of uncovering novel dynamic interaction networks that are critical for influencing the course of medical conditions. Consequently, systems medicine also serves to identify clinically important molecular targets for diagnostic and therapeutic measures against such a condition. PMID- 26357573 TI - Electrostatic Interactions between Complement Regulator CD46(SCR1-2) and Adenovirus Ad11/Ad21 Fiber Protein Knob. AB - Adenoviruses bind to a variety of human cells to cause infection. Both the B2 adenovirus 11 and B1 adenovirus 21 use protein knobs to bind to complement regulator CD46(SCR1-2) in order to gain entry into host cells. In each complex, the two proteins are highly negatively charged but bind to each other at an interface with oppositely charged surface patches. We computationally generated single-alanine mutants of charged residues in the complexes CD46(SCR1-2)-Ad11k and CD46(SCR1-2)-Ad21k. We used electrostatic clustering and Poisson-Boltzmann free energy calculations to propose a hypothesis on the role of electrostatics in association. Our results delineate specific interfacial electrostatic interactions that are critical for association in both CD46(SCR1-2)-Ad11k and CD46(SCR1-2)-Ad21k. These results will serve as a predictive tool in the selection of mutants with desired binding affinity in experimental mutagenesis studies. This study will also serve as a foundation for the design of inhibitors to treat adenovirus infections. PMID- 26357574 TI - The Canadian Cardiac Rehabilitation Registry: Inaugural Report on the Status of Cardiac Rehabilitation in Canada. AB - Introduction. There are over 200 Cardiovascular Rehabilitation (CR) programs in Canada, providing services to more than 50,000 new patients annually. The objective of this study was to describe the impact of CR in Canada. Methods. A retrospective analysis of Canadian CR Registry data is presented. There were 12 programs participating, with 4546 CR participants. Results. The average wait time between patient referral and CR admission was 68 +/- 64 days. Participants were 66.3 +/- 11.5 years old, 71% male, and 82% White. The three leading referral events were coronary artery bypass graft surgery, percutaneous coronary intervention, and acute coronary syndrome. At discharge, data were available for ~90% of participants. Significant improvements in blood pressure (systolic pre-CR 123.5 +/- 17.0, post-CR 121.5 +/- 15.8 mmHg; p < .001), lipids, adiposity, and exercise capacity (peak METs pre-CR 6.5 +/- 2.8, post-CR 7.2 +/- 3.1; p < .001) were observed. However, target attainment for some risk factors was suboptimal. Conclusions. This report provides the first snapshot of the beneficial effects of CR in Canada. Not all patients are equally represented in these programs, however, leaving room for more referral of diverse patients. Greater attainment of risk reduction targets should be pursued. PMID- 26357575 TI - Thioredoxin 1 in Prostate Tissue Is Associated with Gleason Score, Erythrocyte Antioxidant Enzyme Activity, and Dietary Antioxidants. AB - Background. Prostate cancer is the most common noncutaneous cancer and second leading cause of cancer-related mortality in men in the US. Growing evidence suggests that oxidative stress is involved in prostate cancer. Methods. In this study, thioredoxin 1 (Trx 1), an enzyme and subcellular indicator of redox status, was measured in prostate biopsy tissue from 55 men from the North Carolina-Louisiana Prostate Cancer Project. A pathologist blindly scored levels of Trx 1. The association between Trx 1 and the Gleason score, erythrocyte antioxidant enzyme activity, and dietary antioxidant intake was determined using Fisher's exact test. Results. Trx 1 levels in benign prostate tissue in men with incident prostate cancer were positively associated with the Gleason score (P = 0.01) and inversely associated with dietary antioxidant intake (P = 0.03). In prostate cancer tissue, Trx 1 levels were associated with erythrocyte glutathione peroxidase activity (P = 0.01). No association was found for other erythrocyte enzymes. Greater Gleason score of malignant tissue corresponds to a greater difference in Trx 1 levels between malignant and benign tissue (P = 0.04). Conclusion. These results suggest that the redox status of prostate tissue is associated with prostate cancer grade and both endogenous and exogenous antioxidants. PMID- 26357576 TI - Soft Tissue Reconstruction with Free Gingival Graft Technique following Excision of a Fibroma. AB - Background. Oral fibromas are benign, asymptomatic, smooth surfaced, firm structured tumoral lesions that originate from gingival connective tissue or periodontal ligament. Histologically, they are nodular masses characterized by a dense connective tissue, surrounded by stratified squamous epithelium. Case Report. This case report includes the clinical, radiographical, and histological findings and periodontal treatment of a 38-year-old female patient having painless swelling on the gingiva. Intraoral examination revealed a fibrotic, sessile, smooth surfaced gingival overgrowth interdentally between the teeth #13 and #14. Radiographical findings were normal. Initial periodontal treatment (IPT) was applied including oral hygiene instructions, scaling, and root planing. Following IPT, the lesion (0.7 * 0.6 * 0.4 cm) was excised and examined histopathologically. Subsequently, flap operation was performed to have an access to alveolar bone. Surgical site was reconstructed with free gingival graft obtained from hard palate. Hematoxylin-eosin stained sections revealed a nodular mass composed by dense collagen fibers in lamina propria covered by a stratified squamous epithelium, which were consistent with fibroma. Gingival healing was uneventful and without any recurrence during the 12-month follow-up. Conclusions. In order to achieve optimal functional and aesthetical outcomes, free gingival graft can be used for the reconstruction of the wound site after the excision of the fibroma. PMID- 26357577 TI - Scombrotoxinism: Protracted Illness following Misdiagnosis in the Emergency Department. AB - Background. Scombrotoxinism is an acute toxin-induced illness caused primarily by bacterial synthesis of histamine in decomposed fish. Case Report. Immediately after taking 2-3 bites of cooked salmon, a clerical worker developed oral burning, urticaria, and asthma. In the emergency department, she was diagnosed with "allergies"; scombrotoxinism was never considered. She then developed wide ranging symptoms (e.g., chronic fatigue, asthma, anxiety, multiple chemical sensitivity, and paresthesiae) and saw many specialists (in pulmonology, otorhinolaryngology, allergy, toxicology, neurology, psychology, and immunology). During the next 500+ days, she had extensive testing (allergy screens, brain MRI, electroencephalogram, electromyogram, nerve conduction velocity, heavy metal screen, and blood chemistry) with essentially normal results. She filed a workers' compensation claim since this injury occurred following a business meal. She was evaluated by a Qualified Medical Evaluator (GL) on day 504, who diagnosed scombrotoxinism. Comment. Scombrotoxinism should be considered in all patients presenting to the emergency department with "oral burning" or allergy symptoms following "fish consumption." Initial attention to such history would have led to a correct diagnosis and averted this patient's extended illness. Specialist referrals and tests should be ordered only if clinically indicated and not for diagnostic fishing expedition. Meticulous history is crucial in resolving clinical dilemmas. PMID- 26357578 TI - Ulcerating Ileocolitis in Severe Amatoxin Poisoning. AB - Amatoxin poisoning is still associated with a great potential for complications and a high mortality. While the occurrence of acute gastroenteritis within the first 24 hours after amatoxin ingestion is well described, only very few descriptions of late gastrointestinal complications of amatoxin poisoning exist worldwide. We present the case of a 57-year-old female patient with severe amatoxin poisoning causing fulminant but reversible hepatic failure that on day 8 after mushroom ingestion developed severe abdominal pain and watery diarrhea. Ulcerating ileocolitis was identified by computed tomography identifying a thickening of the bowel wall of the entire ileum and biopsies taken from the ileum and large bowel revealing distinct ileitis and proximally accentuated colitis. The absence of discernible alternative etiologies such as infectious agents makes a causal relationship between the ulcerating ileocolitis and the amatoxin poisoning likely. Diarrhea and varying abdominal pain persisted over several weeks and clinical follow-up after six months showed a completely symptom free patient. The case presented highlights the importance to consider the possibility of rare complications of Amanita intoxication in order to be able to respond to them early and adequately. PMID- 26357579 TI - Cepacia Syndrome in a Non-Cystic Fibrosis Patient. AB - Burkholderia (formerly Pseudomonas) cepacia complex is a known serious threat to patients with cystic fibrosis, in whom it has the potential to cause the fatal combination of necrotizing pneumonia, worsening respiratory failure, and bacteremia, known as Cepacia syndrome. The potential for this pathogen to infect non-cystic fibrosis patients is limited and its epidemiology is poorly understood. Previously reported cases of severe Burkholderia cepacia complex lung infection in immunocompetent hosts include pneumonia, bronchiectasis, pyopneumothorax, and cavitary lesions. We present a case of a 64-year-old man with Streptococcus pneumoniae community-acquired pneumonia whose hospital course was complicated by developing cavitary lung lesions, bacteremia, and acute respiratory distress syndrome. Repeated tracheal aspirate and blood cultures grew Burkholderia cepacia. Our case appears to be the first report of Cepacia syndrome in a patient without cystic fibrosis. This report raises concern regarding the potential severity of pulmonary Burkholderia cepacia complex infection and the need to broaden clinicians' suspicion for Cepacia syndrome. A framework to help diagnose and treat infected non-cystic fibrosis individuals may be useful. PMID- 26357580 TI - Silent Spontaneous Uterine Rupture at 36 Weeks of Gestation. AB - Introduction. Silent spontaneous rupture of the uterus before term, with extrusion of an intact amniotic sac and delivery of a healthy neonate, with no maternal or neonatal morbidity or mortality is very rare. Very few cases have been reported in literature. Case Presentation. We report a case of silent spontaneous uterine rupture, found during a scheduled repeat cesarean section at 36 weeks of gestation. Patient had history of two prior classical cesarean sections. She underwent cesarean section, with delivery of a healthy male infant. She had a good postoperative recovery and was discharged on postoperative day 3. Conclusion. Silent spontaneous rupture of the uterus before term with extrusion of an intact amniotic sac is rare. A high index of suspicion and good imaging during pregnancy are important in making this diagnosis. PMID- 26357581 TI - Percutaneous Endoscopic Discectomy via Transforaminal Route for Discal Cyst. AB - Background. Discal cyst has been identified as a rare cause of low back pain and radiating leg pain. The pathogenesis and management of this condition are still debated. The largest number of reported cases had undergone microsurgery while very few cases have been treated with percutaneous endoscopic discectomy (PED). Methods. An 18-year-old boy complained of low back pain radiating to right leg after a minor road traffic accident. Diagnosis of a discal cyst at L4-L5 level was made based on magnetic resonance imaging (MRI). Despite conservative management for 6 months, the low back pain and radiating leg pain persisted so surgical treatment by PED was performed under local anesthesia. As the patient was a very active baseball player, his physician recommended a minimally invasive procedure to avoid damage to the back muscles. Results. The patient's low back pain and leg pain disappeared immediately after surgery and he made a rapid recovery. He resumed mild exercise and sports practice 4 weeks after surgery. Complete regression of the cystic lesion was demonstrated on the 2-month postoperative MRI. Conclusion. A minimal invasive procedure like PED can be an effective surgical treatment for discal cyst, especially in active individuals who play sports. PMID- 26357582 TI - Acute Popliteal Artery Occlusion after Revision Total Knee Arthroplasty. AB - Acute arterial occlusions are a rare complication of total knee arthroplasty (TKA). However, in revision TKA, the risk of such complications is higher and these complications can lead to amputation if not adequately treated. We describe a case of acute popliteal artery occlusion 4 hours after second revision TKA in a patient with a history of several surgical procedures because of periprosthetic infection at a previous hospital. Revascularization was achieved via bypass grafting and amputation was narrowly avoided despite time lag after symptom onset to revascularization. In this case, it was possible that the arterial disease that accompanied the vascular endothelium injury such as pseudoaneurysm had existed since the previous surgery at another hospital and was destroyed by the surgical procedure, which led to the formation of thrombosis and arterial occlusion. Preoperative evaluation of the arterial condition should be considered to avoid acute arterial occlusive disease, especially in patients who had several previous surgical procedures. PMID- 26357583 TI - Changes to Intermediary Metabolites in Sporadic and LRRK2 Parkinson's Disease Demonstrated by Proton Magnetic Resonance Spectroscopy. AB - Background. Parkinson's disease (PD) remains a clinical diagnosis and biomarkers are needed to detect the disease as early as possible. Genetically determined PD provides an opportunity for studying metabolic differences in connection with disease development. Objectives. To study the levels of intermediary metabolites in cerebrospinal fluid (CSF) from patients with PD, either of sporadic type or in carriers of the LRRK2 p.G2019S mutation. Methods. Results from patients with sporadic PD or LRRK2-PD were compared with asymptomatic LRRK2 mutation carriers and healthy control individuals. CSF was analysed by proton MR spectroscopy ((1)H MRS) giving reliable results for 16 intermediary metabolites. Partial least squares discriminant analysis (PLS-DA) was applied to study group differences. Results. PLS-DA distinguished PD patients from healthy individuals based on the metabolites identified in CSF, with 2-hydroxybutyrate, glutamine, and dimethyl sulphone largely contributing to the separations. Conclusion. Speculatively, all three metabolites could alter concentration in response to metabolic changes connected with neurodegeneration; glutamine as a means of removing excess nitrogen from brain, dimethyl sulphone as an anti-inflammatory agent, and 2 hydroxybutyrate in connection with altered glutathione metabolism. Potentially, (1)H-MRS is a promising tool for identifying novel biomarkers for PD. PMID- 26357584 TI - Parkinson's Disease Prevalence and Proximity to Agricultural Cultivated Fields. AB - The risk for developing Parkinson's disease (PD) is a combination of multiple environmental and genetic factors. The Negev (Southern Israel) contains approximately 252.5 km(2) of agricultural cultivated fields (ACF). We aimed to estimate the prevalence and incidence of PD and to examine possible geographical clustering and associations with agricultural exposures. We screened all "Clalit" Health Services members in the Negev (70% of the population) between the years 2000 and 2012. Individual demographic, clinical, and medication prescription data were available. We used a refined medication tracer algorithm to identify PD patients. We used mixed Poisson models to calculate the smoothed standardized incidence rates (SIRs) for each locality. We identified ACF and calculate the size and distance of the fields from each locality. We identified 3,792 cases of PD. SIRs were higher than expected in Jewish rural localities (median SIR [95% CI]: 1.41 [1.28; 1.53] in 2001-2004, 1.62 [1.48; 1.76] in 2005-2008, and 1.57 [1.44; 1.80] in 2009-2012). Highest SIR was observed in localities located in proximity to large ACF (SIR 1.54, 95% CI 1.32; 1.79). In conclusion, in this population based study we found that PD SIRs were higher than expected in rural localities. Furthermore, it appears that proximity to ACF and the field size contribute to PD risk. PMID- 26357585 TI - Inflammation and depression: combined use of selective serotonin reuptake inhibitors and NSAIDs or paracetamol and psychiatric outcomes. AB - BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) and paracetamol have been shown to yield the potential of adjunctive antidepressant treatment effects to selective serotonin reuptake inhibitors (SSRIs); however, when investigating treatment effects of concomitant use, simultaneous evaluation of potential adverse events is important. The objective was thus to investigate treatment effectiveness and safety aspects of concomitant SSRI use with NSAIDs or paracetamol. METHODS: Within a 25% random sample of the Danish population, we identified all incident SSRI users between 1997 and 2006 (N = 123,351). Effectiveness and safety measures were compared between periods of SSRI use only and periods of combined SSRI and NSAID or paracetamol use by applying Cox regression. RESULTS: Among 123,351 SSRI users (follow-up: 53,697.8 person-years), 21,666 (17.5%) used NSAIDs and 10,232 (8.3%) paracetamol concomitantly. Concomitant NSAID use increased the risk of any psychiatric contact [Hazard rate ratio (95%-confidence interval): 1.22 (1.07; 1.38)] and with depression [1.31 (1.11; 1.55)]. Low-dose acetylsalicylic acid reduced the risk of psychiatric contact in general [0.74 (0.56; 0.98)] and with depression [0.71 (0.50; 1.01)]. Ibuprofen reduced the risk of psychiatric contacts [0.76 (0.60; 0.98)]. Concerning safety, paracetamol was associated with increased mortality [3.18 (2.83; 3.58)], especially cardiovascular [2.51 (1.93; 3.28)]. Diclofenac [1.77 (1.22; 2.55)] and the selective COX-2 inhibitors [1.75 (1.21; 2.53)] increased mortality risks. CONCLUSIONS: Concomitant use of SSRIs and NSAIDs occurred frequently, and effectiveness and safety outcomes varied across individual NSAIDs. Especially low-dose acetylsalicylic acid may represent an adjunctive antidepressant treatment option. The increased mortality risk of concomitant use of paracetamol needs further investigation. PMID- 26357586 TI - Lipopolysaccharide potentiates hyperthermia-induced seizures. AB - BACKGROUND: Prolonged febrile seizures (FS) have both acute and long-lasting effects on the developing brain. Because FS are often associated with peripheral infection, we aimed to develop a preclinical model of FS that simulates fever and immune activation in order to facilitate the implementation of targeted therapy after prolonged FS in young children. METHODS: The innate immune activator lipopolysaccharide (LPS) was administered to postnatal day 14 rat (200 MUg/kg) and mouse (100 MUg/kg) pups 2-2.5 h prior to hyperthermic seizures (HT) induced by hair dryer or heat lamp. To determine whether simulation of infection enhances neuronal excitability, latency to seizure onset, threshold temperature and total number of seizures were quantified. Behavioral seizures were correlated with electroencephalographic changes in rat pups. Seizure-induced proinflammatory cytokine production was assessed in blood samples at various time points after HT. Seizure-induced microglia activation in the hippocampus was quantified using Cx3cr1(GFP/+) mice. RESULTS: Lipopolysaccharide priming increased susceptibility of rats and mice to hyperthemic seizures and enhanced seizure-induced proinflammatory cytokine production and microglial activation. CONCLUSIONS: Peripheral inflammation appears to work synergistically with hyperthermia to potentiate seizures and to exacerbate seizure-induced immune responses. By simulating fever, a regulated increase in body temperature from an immune challenge, we developed a more clinically relevant animal model of prolonged FS. PMID- 26357587 TI - Blood pressure differences between patients with lacunar and nonlacunar infarcts. AB - BACKGROUND: Elevated blood pressure is frequently seen in acute stroke, and patients with lacunar and nonlacunar infarcts may have different underlying mechanisms for increase in blood pressure. The impact of hypertension as a risk factor may also vary. The aims of the present study were to investigate blood pressure in patients presenting with lacunar syndromes but with different anatomical subtypes of stroke, to explore the impact of subtype on blood pressure, and to identify stroke-related factors associated with hypertension. METHODS: Consecutive patients presenting with an acute lacunar syndrome were enrolled. Patients were classified into a lacunar or nonlacunar group based on radiological verified infarcts. Blood pressure was measured. Between-group differences were analyzed by chi2-test, t-test, and Mann-Whitney U test, as appropriate. We performed linear regression to analyze the association between blood pressure and lacunar infarct, and multiple linear regression to adjust for other covariates. RESULTS: One hundred thirteen patients were included. Seventy five percent had lacunar and 25% nonlacunar infarcts. There was no significant difference in clinical severity between the two groups. In the linear regression model, we found a significant association between blood pressure and lacunar infarct. No other factor was significantly associated with blood pressure in the two groups. CONCLUSIONS: Lacunar infarcts may be independently associated with higher blood pressure compared to nonlacunar infarcts with the same clinical severity. Blood pressure differences between different subtypes of stroke may not be related to clinical severity but to the underlying cause of stroke. PMID- 26357589 TI - Erythropoietin produced by genetic-modified NIH/3T3 fibroblasts enhances the survival of degenerating neurons. AB - BACKGROUND: Erythropoietin (EPO) has potent neuroprotective effects. The short term delivery of high-dose EPO seemed to improve patients' neuromuscular functions; however, excessive EPO resulted in systematically high hematocrit and thrombotic risk. In our study, we established a cellular material for future in vivo studies of neurodegenerative diseases based on EPO provided regionally at a nontoxic level. METHODS: A mouse EPO cDNA was subcloned into the pCMS-EGFP vector and transfected into NIH/3T3 fibroblasts to design a biological provider that can regionally release EPO for the treatment of neurological diseases. After G418 selection, a stable EPO-overexpressing cell line, EPO-3T3-EGFP, was established. To further confirm the neuroprotective abilities of secreted EPO from EPO-3T3 EGFP cells, a cell model of neurodegeneration, PC12-INT-EGFP, was applied. RESULTS: The expression level of EPO was highly elevated in EPO-3T3-EGFP cells, and an abundant amount of EPO secreted from EPO-3T3-EGFP cells was detected in the extracellular milieu. After supplementation with conditioned medium prepared from EPO-3T3-EGFP cells, the survival rate of PC12-INT-EGFP cells was significantly enhanced. Surprisingly, a fraction of aggregated cytoskeletal EGFP tagged alpha-internexin in PC12-INT-EGFP cells was disaggregated and transported into neurites dynamically. The immunocytochemical distribution of IF proteins, including NF-M, phosphorylated-NF-M, and the alpha-INT-EGFP fusion protein, were less aggregated in the perikaryal region and transported into neurites after the EPO treatment. CONCLUSION: The established EPO-overexpressing NIH/3T3 cell line, EPO-3T3-EGFP, may provide a material for future studies of cell-based therapies for neurodegenerative diseases via the secretion of EPO on a short-term, high dose, regional basis. PMID- 26357588 TI - Downregulation of Gabra4 expression during alcohol withdrawal is mediated by specific microRNAs in cultured mouse cortical neurons. AB - BACKGROUND: Alcohol abuse and dependence are a serious public health problem. A large number of alcohol-regulated genes, (ARGs) are known to be influenced by alcohol use and withdrawal (AW), and recent evidence suggests that neuroadaptation to alcohol may be due in part to epigenetic changes in the expression of ARGs. Gabra4, which encodes the alpha4 subunit of GABAA receptors (GABAARs), is one of a number of ARGs that show remarkable plasticity in response to alcohol, being rapidly upregulated by acute alcohol exposure. This study addressed the effects of AW on changes in the expression of Gabra4 and related genes that encode other subunits of GABAARs, and the potential regulation of Gabra4 by microRNAs. METHODS: We studied gene and microRNAs expression, using RT PCR and microRNA microarray in cultured cortical neurons treated with alcohol, which was then removed in order to simulate AW in vitro. We also used microRNA mimics or inhibitors, and a promoter-reporter construct carrying the 3'UTR of Gabra4. RESULTS: Eleven hours after removal of alcohol, Gabra4 was downregulated, with a modest increase in the expression of Gabrg2, but no change in the expression of Gabra1, Gabrd, or Gabrb2. microRNA profiling in neurons undergoing AW revealed upregulation in the expression of miR-155, miR-186, miR-24, and miR 375 after 8 h of AW. Transfection with molecular mimics of miR-186, miR-24, or miR-375 also downregulated Gabra4 expression, whereas transfection with the corresponding inhibitors of these microRNAs normalized Gabra4 expression in AW neurons to the level measured in control neurons. Promoter-reporter experiments supported the idea that miR-155, miR-186, miR-24, miR-27b, or miR-375 bind to the 3'UTR of Gabra4 and thereby inhibit protein production. CONCLUSIONS: Our data suggest that AW decreases Gabra4 expression, and that this may be mediated in part by the induction of specific microRNAs in cortical neurons during AW. PMID- 26357590 TI - Blunted responses to reward in remitted post-traumatic stress disorder. AB - BACKGROUND: Recent evidence suggests blunted responses to rewarding stimuli in patients with post-traumatic stress disorder (PTSD). However, it is not clear whether these alterations in reward processing normalize in remitted PTSD patients. METHODS: We tested behavioral and physiological responses to monetary reward in a spatial memory task in 13 accident survivors with remitted PTSD, 14 accident survivors who never had PTSD, and 16 nontrauma-exposed subjects. All accident survivors were recruited from two samples of severely physically injured patients, who had participated in previous prospective studies on the incidence of PTSD after accidental injury approximately 10 years ago. Reaction time, accuracy, skin conductance responses, and self-reported mood were assessed during the task. RESULTS: Accident survivors who never had PTSD and nontrauma exposed controls reported significantly higher positive mood in the reinforced versus nonreinforced condition (P < 0.045 and P < 0.001, respectively), while there was no effect of reinforcement in remitted PTSD subjects. CONCLUSIONS: Our findings suggest an alteration of the reward system in remitted PTSD. Further research is needed to investigate whether altered reward processing is a residual characteristic in PTSD after remission of symptoms or, alternatively, a preexisting risk factor for the development of PTSD after a traumatic event. PMID- 26357591 TI - Delayed posthypoxic leukoencephalopathy: a case series and review of the literature. AB - BACKGROUND: Delayed posthypoxic leukoencephalopathy (DPHL) is a rare and underrecognized entity where patients manifest a neurological relapse after initial recovery from an acute hypoxic episode. We sought to describe the magnetic resonance imaging (MRI) findings in a group of patients with DPHL and review the available literature. METHODS: Retrospective case series including patients who presented with neurological and/or psychiatric symptoms after recovery from an acute hypoxic episode. The history and clinical presentation were reviewed from the electronic medical records. MRI scans were evaluated from the picture archiving and communication system. We performed a comprehensive review of the English medical literature for prior published cases of DPHL and describe the key imaging findings that have been reported related to this condition. RESULTS: A total of five patients were identified, including four patients with respiratory failure due to drug overdoses from benzodiazepines, opioids, and/or barbiturates, and one patient who presented after cardiopulmonary arrest due to pulmonary embolism. All patients showed diffuse, extensive, and confluent white matter signal abnormalities including prominent restricted diffusion, extending to the subcortical white matter and respecting the U-fibers. There was no gyral edema or contrast enhancement. In one case histopathology was available, which highlighted patchy subcortical myelin loss with sparing of U fibers and demonstrated prominent macrophage/microglial inflammation with extensive axonal damage. Of the other four patients, two were at their neurological baselines and two had persistent neurological deficits at the time of discharge. CONCLUSIONS: The described constellation of MRI findings is highly suggestive of DPHL in the appropriate clinical setting. PMID- 26357593 TI - Adaptation of the Critical Care Family Need Inventory to the Turkish population and its psychometric properties. AB - In the complex environment of intensive care units, needs of patients' relatives might be seen as the lowest priority. On the other hand, because of their patients' critical and often uncertain conditions, stress levels of relatives are quite high. This study aims to adapt the Critical Care Family Need Inventory, which assesses the needs of patients' relatives, for use with the Turkish speaking population and to assess psychometric properties of the resulting inventory. The study was conducted in a state hospital with the participation of 191 critical care patient relatives. Content validity was assessed by expert opinions, and construct validity was examined by exploratory factor analysis (EFA). Cronbach's alpha coefficient was used to determine internal consistency. The translated inventory has a content validity ratio higher than the minimum acceptable level. Its construct validity was established by the EFA. Cronbach's alpha coefficient for the entire scale was 0.93 and higher than 0.80 for subscales, thus demonstrating the translated version's reliability. The Turkish adaptation appropriately reflects all dimensions of needs in the original CCFNI, and its psychometric properties were acceptable. The revised tool could be useful for helping critical care healthcare workers provide services in a holistic approach and for policymakers to improve quality of service. PMID- 26357594 TI - Perilipin-related protein regulates lipid metabolism in C. elegans. AB - Perilipins are lipid droplet surface proteins that contribute to fat metabolism by controlling the access of lipids to lipolytic enzymes. Perilipins have been identified in organisms as diverse as metazoa, fungi, and amoebas but strikingly not in nematodes. Here we identify the protein encoded by the W01A8.1 gene in Caenorhabditis elegans as the closest homologue and likely orthologue of metazoan perilipin. We demonstrate that nematode W01A8.1 is a cytoplasmic protein residing on lipid droplets similarly as human perilipins 1 and 2. Downregulation or elimination of W01A8.1 affects the appearance of lipid droplets resulting in the formation of large lipid droplets localized around the dividing nucleus during the early zygotic divisions. Visualization of lipid containing structures by CARS microscopy in vivo showed that lipid-containing structures become gradually enlarged during oogenesis and relocate during the first zygotic division around the dividing nucleus. In mutant embryos, the lipid containing structures show defective intracellular distribution in subsequent embryonic divisions and become gradually smaller during further development. In contrast to embryos, lipid containing structures in enterocytes and in epidermal cells of adult animals are smaller in mutants than in wild type animals. Our results demonstrate the existence of a perilipin-related regulation of fat metabolism in nematodes and provide new possibilities for functional studies of lipid metabolism. PMID- 26357595 TI - Large-scale assessment of olfactory preferences and learning in Drosophila melanogaster: behavioral and genetic components. AB - In the Evolve and Resequence method (E&R), experimental evolution and genomics are combined to investigate evolutionary dynamics and the genotype-phenotype link. As other genomic approaches, this methods requires many replicates with large population sizes, which imposes severe restrictions on the analysis of behavioral phenotypes. Aiming to use E&R for investigating the evolution of behavior in Drosophila, we have developed a simple and effective method to assess spontaneous olfactory preferences and learning in large samples of fruit flies using a T-maze. We tested this procedure on (a) a large wild-caught population and (b) 11 isofemale lines of Drosophila melanogaster. Compared to previous methods, this procedure reduces the environmental noise and allows for the analysis of large population samples. Consistent with previous results, we show that flies have a preference for orange vs. apple odor. With our procedure wild derived flies exhibit olfactory learning in the absence of previous laboratory selection. Furthermore, we find genetic differences in the olfactory learning with relatively high heritability. We propose this large-scale method as an effective tool for E&R and genome-wide association studies on olfactory preferences and learning. PMID- 26357596 TI - A retrospective study on the outcomes of cataract surgery in an Eastern Regional Health Authority hospital of Trinidad and Tobago. AB - Background. Worldwide, cataract is a major cause of blindness. The paper aims to evaluate factors associated with borderline and poor outcomes of cataract surgery at an Eastern Regional Health Authority (ERHA) hospital in Trinidad and Tobago. Materials and Methods. A hospital-based, retrospective study was done on 401 patients who had undergone cataract surgery (unilateral and bilateral) at an ERHA Hospital between March 2009 and September 2014. Data was collected on variables concerning demographic, medical history, surgical history, ocular findings and visual acuity (VA). The outcome variable of interest was Snellen's post-operative (presenting) VA which was transformed into a dichotomous variable with borderline and poor outcomes as one and good outcomes as the other. Data were analysed using univariate and multivariate logistic regression analyses. Results. Good outcome (presenting VA 6/18 or better) was seen in 350 (67%) eyes. The fitted model consisted of ocular co-morbidity (OR =2.133; 95% CI [1.346-3.380]), hypertension (OR = 0.520; 95% CI [0.381-0.928]), surgical procedure (OR = 1.56; 95% CI [1.004 2.425]), good preoperative VA (OR = 0.388, 95% CI [0.211-0.714]), borderline preoperative VA (OR = 0.485; 95% CI = [0.278-0.843]) and year of first visit to clinic (OR = 2.243; 95% CI [1.215-4.141]). Conclusion. There is a need for community-based outreach to increase awareness of eye health and diseases. It is recommended that the general population is encouraged to take responsibility for personal management. The facilities at the Hospital should also be enhanced. PMID- 26357597 TI - Assessing uncertainty in sighting records: an example of the Barbary lion. AB - As species become rare and approach extinction, purported sightings can be controversial, especially when scarce management resources are at stake. We consider the probability that each individual sighting of a series is valid. Obtaining these probabilities requires a strict framework to ensure that they are as accurately representative as possible. We used a process, which has proven to provide accurate estimates from a group of experts, to obtain probabilities for the validation of 32 sightings of the Barbary lion. We consider the scenario where experts are simply asked whether a sighting was valid, as well as asking them to score the sighting based on distinguishablity, observer competence, and verifiability. We find that asking experts to provide scores for these three aspects resulted in each sighting being considered more individually, meaning that this new questioning method provides very different estimated probabilities that a sighting is valid, which greatly affects the outcome from an extinction model. We consider linear opinion pooling and logarithm opinion pooling to combine the three scores, and also to combine opinions on each sighting. We find the two methods produce similar outcomes, allowing the user to focus on chosen features of each method, such as satisfying the marginalisation property or being externally Bayesian. PMID- 26357598 TI - Production of medium-chain volatile flavour esters in Pichia pastoris whole-cell biocatalysts with extracellular expression of Saccharomyces cerevisiae acyl CoA:ethanol O-acyltransferase Eht1 or Eeb1. AB - Medium-chain volatile flavour esters are important molecules since they have extensive applications in food, fragrance, cosmetic, paint and coating industries, which determine different characteristics of aroma or taste in commercial products. Biosynthesis of these compounds by alcoholysis is catalyzed by acyl-CoA:ethanol O-acyltransferases Eht1 or Eeb1 in Saccharomyces cerevisiae. In this study, these two yeast enzymes were selected to explore their preparations as the form of whole cell biocatalysts for the production of volatile flavour esters. Here, the novel whole cell biocatalysts Pichia pastoris yeasts with functional extracellular expression of Eht1 or Eeb1 were constructed. Flavour production was established through an integrated process with coupled enzyme formation and ester biosynthesis in the recombinant yeasts in one pot, leading to the formation of volatile C6-C14 methyl and ethyl esters from wort medium. Interestingly, there is no significant difference between P. pastoris EHT1 and P. pastoris-EEB1 in substrate preference during flavour biosynthesis, indicating a similar role of Eht1 and Eeb1 in P. pastoris cells, in contradiction with previous findings in S. cerevisiae to some extent. Consequently the study not only provides a greater understanding of these two enzymes in a heterogeneous host, but also demonstrated the positive effect of the recombinant Eht1 and Eeb1 in ester formation by P. pastoris live cells, potentially paving the way towards achieving efficient production of volatile flavour by an integrated biocatalytic system composed of recombinant enzyme production and flavour biosynthesis. PMID- 26357599 TI - Magneto-structural coupling in [Formula: see text]. AB - [Formula: see text] compound is well Known to show the frustration of the spin structure. At 12 K, [Formula: see text] distorts to break symmetry of the degenerated frustrated spin states by the spin-Peierls-like phase transition, accompanying with the antiferromagnetic ordering. On the other hand, [Formula: see text] undergoes a Jahn-Teller phase transition at a temperature of 310 K, differing from the low temperature ferrimagnetic transition temperature [Formula: see text] of about 60 K. It is also reported that [Formula: see text] shows another magnetic phase transition at about 30 K. These two phase transitions accompanying with the lattice change can be understood by the magneto-elastic interactions. Two interactions, the Jahn-Teller interaction and the spin-Peierls like interaction are co-exist in [Formula: see text] system. In this report the [Formula: see text] compounds with x = 0.8, 0.6 and 1 are investigated by the X ray diffraction measurements. From these measurements the crystal structures are determined. The full width at half maximum and integrated intensity give the fruitful information for magnetic elastic interactions. PMID- 26357600 TI - Nation related participation and performance trends in 'Norseman Xtreme Triathlon' from 2006 to 2014. AB - We investigated the nation related participation and performance trends in triathletes competing in 'Norseman Xtreme Triathlon' between 2006 and 2014 using mixed models, one-way analysis of variance and multi-variate regression analyses. A total of 1594 athletes (139 women and 1455 men) originating from 34 different countries finished the race. Most of the athletes originated from Norway, Germany, Great Britain, Sweden, USA and France. In the mixed model analysis considering all finishers (n = 1594), with calendar year, sex and country as independent and overall race time as dependent variable, calendar year (p < 0.0001), sex (p < 0.0001), country (p < 0.0001) and the interaction sex * calendar year (p = 0.012) were significant. In the model where overall race time was separated in the three disciplines, we found interactions such as country * discipline (p < 0.0001), year * discipline (p < 0.0001), sex * discipline (p < 0.0001), calendar year * sex (p = 0.044), calendar year * sex * discipline (p = 0.031). Overall race time decreased every year, above all in the year 2012. Women were slower than men, but women reduced this gender gap year after year and above all in the year 2007 (p = 0.001). Athletes from Norway and Germany were faster than those from Great Britain and other countries. Split times of the discipline decreased throughout the years. In particular, the discipline having more impact on overall race time was cycling. Most of the podiums were achieved by Norwegian women and men. For women, the fastest split and transition times were achieved by Norwegian women with exception of the run where German women were faster. Norwegian men were the fastest in split and transition times although French athletes were the fastest in swimming. Across years, the annual three fastest Norwegian women improved in cycling, running, overall race time and transition times but not Norwegian and German men. British men, however, improved running split times and transition times. To summarize, most of the finishers in 'Norseman Xtreme Triathlon' originated from Norway and the fastest race times were achieved by Norwegian women and men. Norwegian women improved race times across years but not Norwegian men. PMID- 26357601 TI - Depression screening and advisory service provided by community pharmacist for depressive students in university. AB - BACKGROUND: Depressive symptom among adolescent is prevalent but advisory service for this symptom is limited, particularly in university. OBJECTIVES: (1) To identify depressive students in health science faculties, (2) To evaluate the consequence of depression advisory service by community pharmacist, compared between a group counseling and an individual one. METHODS: A two-phase study was designed-a cross-sectional study followed by an experimental study. Health science students were screened by CES-D questionnaire. The prevalence and predictors of depressed mood were determined. Depressive students were then invited to the experimental study. Participants were assigned into 2 groups, by stratified random sampling, and followed up for 16 weeks. Group 1 received a group counselling, group 2 received an individual counselling from a trained pharmacist. Outcomes measured were the CES-D score and quality of life. RESULTS: The prevalence of depressed mood students was 13.7 % (195/1421). Students in year 2nd and year 3rd, nursing and medicine students, and GPA were strongly associated with the CES-D score (P < 0.05). Sixty-eight depressive students were assigned into the experiment. The CES-D scores of both groups were significantly reduced from the baseline (P < 0.001). The post-test score of group 2 was lower than group 1 (17.7 +/- 4.5 vs 20.1 +/- 4.6, P = 0.038). At week 16, both counselling types significantly increased mean score of physical health (P < 0.001) whereas score of mental health was increased significantly only by the individual counselling, from 37.9 +/- 9.9 to 43.1 +/- 8.4 (P = 0.036). CONCLUSIONS: Depressive symptom among health science students is considerably high. Year of study, faculty and GPA are significant predictors of this disorder. Trained community pharmacists can effectively screen and provide advisory service. Individual counseling is more effective than using group advice. PMID- 26357603 TI - The Discovery and Development of Boceprevir: A Novel, First-generation Inhibitor of the Hepatitis C Virus NS3/4A Serine Protease. AB - An estimated 2-3% of the world's population is infected with hepatitis C virus (HCV), making it a major global health problem. Consequently, over the past 15 years, there has been a concerted effort to understand the pathophysiology of HCV infection and the molecular virology of replication, and to utilize this knowledge for the development of more effective treatments. The virally encoded non-structural serine protease (NS3) is required to process the HCV polyprotein and release the individual proteins that form the viral RNA replication machinery. Given its critical role in the replication of HCV, the NS3 protease has been recognized as a potential drug target for the development of selective HCV therapies. In this review, we describe the key scientific discoveries that led to the approval of boceprevir, a first-generation, selective, small molecule inhibitor of the NS3 protease. We highlight the early studies that reported the crystal structure of the NS3 protease, its role in the processing of the HCV polyprotein, and the structural requirements critical for substrate cleavage. We also consider the novel attributes of the NS3 protease-binding pocket that challenged development of small molecule inhibitors, and the studies that ultimately yielded milligram quantities of this enzyme in a soluble, tractable form suitable for inhibitor screening programs. Finally, we describe the discovery of boceprevir, from the early chemistry studies, through the development of high-throughput assays, to the phase III clinical development program that ultimately provided the basis for approval of this drug. This latest phase in the development of boceprevir represents the culmination of a major global effort to understand the pathophysiology of HCV and develop small molecule inhibitors for the NS3 protease. PMID- 26357602 TI - Update on the Development of Anti-Viral Agents Against Hepatitis C. AB - Hepatitis C virus (HCV) infects nearly 170 million people worldwide and causes chronic hepatitis, cirrhosis, and hepatocellular carcinoma. The search for a drug regimen that maximizes efficacy and minimizes side effects is quickly evolving. This review will discuss a wide range of drug targets currently in all phases of development for the treatment of HCV. Direct data from agents in phase III/IV clinical trials will be presented, along with reported side-effect profiles. The mechanism of action of all treatments and resistance issues are highlighted. Special attention is given to available trial data supporting interferon-free treatment regimens. HCV has become an increasingly important public health concern, and it is important for physicians to stay up to date on the rapidly growing novel therapeutic options. PMID- 26357604 TI - Advances in Nucleotide Antiviral Development from Scientific Discovery to Clinical Applications: Tenofovir Disoproxil Fumarate for Hepatitis B. AB - Exploration of naturally occurring chemical structures for medicinal uses has received significant interest in drug discovery and development research in the past few decades. None have had more success or products of greater clinical efficacy than synthetic analogs of nucleosides and nucleotides, especially as antiviral drugs. Nucleos(t)ide antivirals are synthetic analogs of the natural building blocks of DNA or RNA. This review focuses on the developmental path of tenofovir disoproxil fumarate (TDF), a prodrug of a nucleotide analog and its clinical applications as a first-line antiviral for chronic hepatitis B (CHB). Tenofovir is a potent antiviral compound, but has poor oral availability. The disoproxil fumarate (DF) prodrug moiety greatly enhances intestinal absorption allowing it to become an oral medication. Tenofovir is activated intracellularly, and the incorporation into HBV DNA prevents further elongation thus terminating replication. In patients with CHB, TDF has demonstrated broad, potent and sustained virologic response. Maintenance of viral suppression for up to 5 years resulted in regression of fibrosis and cirrhosis. No tenofovir-resistant HBV variants have been detected in patients after long-term use. The efficacy and safety profiles reported from cohort studies of clinical practices were consistent with those observed in registration trials. Continuous development includes a new oral prodrug, tenofovir alafenamide fumarate (TAF), which has enhanced delivery of tenofovir to target cells compared to TDF. PMID- 26357605 TI - Polymorphism Near the Interleukin-28B Gene and Anti-Hepatitis C Viral Response. AB - In a recent genome-wide association study, single nucleotide polymorphisms (SNPs) located near the interleukin-28B gene (IL28B), which encodes type III interferon (IFN) lambda3, were shown to be strongly associated with a viral response to pegylated IFNalpha (PEG-IFNalpha) and ribavirin (RBV) combination therapy and spontaneous viral clearance in patients chronically and acutely infected with hepatitis C virus (HCV), respectively. The global distribution of allele frequencies shows a remarkable pattern, in which a favorable allele is nearly fixed in East Asia, has an intermediate frequency in Europe, and is least frequent in Africa. Although the underlying mechanisms responsible for viral responses associated with IL28B SNPs have not been completely elucidated, IFN stimulated gene expression in patients with unfavorable IL28B genotypes tends to be high at baseline and is insufficiently induced by exogenous IFN administration, resulting in poor treatment outcomes. Clinically, triple therapy with PEG-IFNalpha/RBV together with direct-acting antiviral agents (DAAs) is currently used to treat chronic hepatitis C as a first-line therapy. Although the predictive power of IL28B status may be attenuated, the IL28B genotype will remain relevant to the outcomes of DAA therapy when used in combination with PEG IFNalpha as a backbone. Even with the introduction of IFN-free therapies with a new class of highly effective DAAs, IL28B SNPs are still useful predictors of treatment outcomes and can be used to individualize treatment strategies to maximize cost-effectiveness and identify patients at risk of being refractory to treatment. This review summarizes the current understanding of the clinical significance and role of IL28B in HCV infection and response to therapy. PMID- 26357606 TI - Genome-Wide Association Study Reveals Host Genetic Factors for Liver Diseases. AB - A number of disease-associated genetic markers for common liver diseases have been identified using genome-wide association studies (GWASs). The GWAS strategy is based on genome-wide single-nucleotide polymorphism typing technologies, which are now commercially available, accompanied by statistical methods to identify host genetic factors that are associated with target diseases or complex genetic traits. One of the most striking features of the GWAS strategy is the ability to identify unexpected disease-associated genetic markers across the entire human genome. Here, we describe the technological aspects of the GWAS strategy with examples from actual GWAS reports related to hepatitis research, including drug response for patients with chronic hepatitis C, susceptibility to primary biliary cirrhosis, and hepatitis-B-related hepatocellular carcinoma. PMID- 26357607 TI - The Discovery and Development of a Potent Antiviral Drug, Entecavir, for the Treatment of Chronic Hepatitis B. AB - Since the first approval of interferon for the treatment of chronic hepatitis B virus (HBV) infection in 1992, six additional antivirals have been developed: pegylated interferon-alfa2a, and the oral antivirals lamivudine, adefovir, telbivudine, entecavir and tenofovir. The availability of animal models for HBV infection and hepatocyte cell culture led to the discovery and development of oral antivirals targeted at HBV polymerase and reverse transcriptase, which inhibit viral replication. The discovery and development of entecavir, the first oral anti-HBV drug with both potent antiviral activity and a high genetic barrier to resistance, took more than 10 years before it was first approved in the USA. Since then, multiple real-life studies have provided data consistent with the findings of the registration trials and the long-term rollover study in terms of efficacy, resistance, and safety. Data from the long-term follow-up of patients enrolled in the registration studies showed that treatment with entecavir can lead to significant improvements in liver histopathology, and recent cohort studies have demonstrated that treatment with entecavir may reduce disease progression and the development of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B. In addition, real-life studies suggest that entecavir may reduce HCC recurrence and increase survival rates in patients with HBV related HCC post-surgical resection. PMID- 26357608 TI - Drug- and Herb-Induced Liver Injury in Clinical and Translational Hepatology: Causality Assessment Methods, Quo Vadis? AB - Drug-induced liver injury (DILI) and herb-induced liver injury (HILI) are typical diseases of clinical and translational hepatology. Their diagnosis is complex and requires an experienced clinician to translate basic science into clinical judgment and identify a valid causality algorithm. To prospectively assess causality starting on the day DILI or HILI is suspected, the best approach for physicians is to use the Council for International Organizations of Medical Sciences (CIOMS) scale in its original or preferably its updated version. The CIOMS scale is validated, liver-specific, structured, and quantitative, providing final causality grades based on scores of specific items for individual patients. These items include latency period, decline in liver values after treatment cessation, risk factors, co-medication, alternative diagnoses, hepatotoxicity track record of the suspected product, and unintentional re-exposure. Provided causality is established as probable or highly probable, data of the CIOMS scale with all individual items, a short clinical report, and complete raw data should be transmitted to the regulatory agencies, manufacturers, expert panels, and possibly to the scientific community for further refinement of the causality evaluation in a setting of retrospective expert opinion. Good-quality case data combined with thorough CIOMS-based assessment as a standardized approach should avert subsequent necessity for other complex causality assessment methods that may have inter-rater problems because of poor-quality data. In the future, the CIOMS scale will continue to be the preferred tool to assess causality of DILI and HILI cases and should be used consistently, both prospectively by physicians, and retrospectively for subsequent expert opinion if needed. For comparability and international harmonization, all parties assessing causality in DILI and HILI cases should attempt this standardized approach using the updated CIOMS scale. PMID- 26357609 TI - Hepatic Sarcoidosis. AB - Sarcoidosis is a multisystem disease characterized by the presence of non caseating granulomas in affected organs. Pulmonary involvement is the most common site of disease activity. However, hepatic involvement is also common in sarcoidosis, occurring in up to 70% of patients. Most patients with liver involvement are asymptomatic. Therefore, the majority of cases are discovered incidentally, frequently by the finding of elevated liver enzymes. Pain in the right upper quadrant of the abdomen, fatigue, pruritus, and jaundice may be associated with liver involvement. Portal hypertension and cirrhosis are complications linked to long-standing hepatic sarcoidosis. Liver biopsy is usually required to confirm the diagnosis. It is important to differentiate hepatic sarcoidosis from other autoimmune and granulomatous liver diseases. Not all cases of hepatic sarcoidosis require treatment. For symptomatic patients, the first line treatment includes corticosteroids or ursodeoxycholic acid. Various immunosuppressant agents can be used as second line agents. Rarely, severe cases require liver transplantation. PMID- 26357610 TI - Peginterferon Lambda-1a, a New Therapeutic for Hepatitis C Infection, from Bench to Clinic. AB - Chronic infection with hepatitis C virus (HCV) is estimated to affect approximately 3% of the world's population and cause 350,000 deaths each year. For a number of years, the standard of care has been combination therapy with recombinant alfa interferons-originally as native proteins but more recently as polyethyleneglycol-modified derivatives-and ribavirin, with the recent addition of an NS3 protease inhibitor for HCV genotype 1. However, therapeutic alfa interferons are associated with a significant burden of treatment-limiting adverse events, including musculoskeletal and influenza-like symptoms, hematologic cytopenias, autoimmune disease, fatigue, and other neurologic events. In 2003, a team at ZymoGenetics (now a fully owned subsidiary of Bristol-Myers Squibb) and a second, independent group simultaneously identified a new class of interferons-the type III lambda interferons-with near-identical activity to the type I alfa interferons in hepatocytes but with an unrelated and less ubiquitous receptor. Subsequent evaluation of the type III interferon system demonstrated antiviral activity against HCV in vitro with limited activity in peripheral blood mononuclear cells and other nonhepatocyte cell types, supporting its development as a potentially better-tolerated therapy for viral hepatitis. Peginterferon lambda-1a (Lambda) is an investigational type III therapeutic agent originally developed at ZymoGenetics that is currently in Phase 3 studies for the treatment of HCV. In this review, we describe the selection of the Lambda molecule and its preclinical and early clinical development, and how the resulting data have helped to establish the differentiated safety profile for Lambda-with fewer influenza-like and musculoskeletal symptoms and less hematologic toxicity than the alfa interferons-that was seen in later studies. PMID- 26357611 TI - Environmental Exposures and Hepatocellular Carcinoma. AB - Infection with hepatitis B and/or hepatitis C virus is a well-established risk factor for the development of hepatocellular carcinoma (HCC). However, it is now clear that certain occupational, environmental, and lifestyle factors also play a role in cancer development. Among these factors are smoking, alcohol consumption, workplace exposure to vinyl chloride, and exposure to polycylic aromatic hydrocarbons and aflatoxins. There is also evidence that several other chemical and infectious agents have a role in inducing HCC in humans. Epidemiologic studies and the use of biomarkers have provided essential data to demonstrate the importance of some of these factors in human risk, while animal studies have suggested that other chemicals may also play a role. Although immunization against hepatitis B virus infection remains the primary method of preventing HCC in regions of the world where this virus is a primary etiologic agent, there is currently no vaccine for hepatitis C virus. Thus, limiting exposure to other known risk factors remains an important mechanism in preventing HCC. PMID- 26357612 TI - Liver Diseases and Autoimmunity. PMID- 26357613 TI - Autochthonous Hepatitis E Virus Infection in Europe: A Matter of Concern for Public Health? AB - Human hepatitis E virus (HHEV) is the proposed name for a diverse group of RNA viruses from the family Hepeviridae that cause acute hepatitis among humans. Waterborne strains are regularly imported into Europe by international travelers, and virus transmission of zoonotic strains via contaminated aliments is involved in autochthonous cases. Therefore, in Europe, hepatitis E displays a unique dual character, having features of both imported and autochthonous infections. Environmental involvement of waterborne and zoonotic diseases puts alimentary safety at risk. In addition, it may lead to serious health problems derived from persistent infection among patients with immune impairment due to organ transplant, cancer, or human immunodeficiency virus infection. Although the European health authorities know at present that HHEV represents a problem worthy of consideration, the actual incidence of the disease in Europe is unknown, and attempts to ascertain the prevalence of the infection is hampered by unresolved technical issues. In order to determine the burden of hepatitis E in Europe, the World Health Organization Regional Office and the European Centre for Disease Prevention and Control should pay specific attention to hepatitis E, and research efforts in the continent should be transnational and collaborative. Development of a specific European network for hepatitis E would help to achieve these goals. PMID- 26357614 TI - Proteome Analyses of Hepatocellular Carcinoma. AB - Proteomics has evolved into a powerful and widely used bioanalytical technique in the study of cancer, especially hepatocellular carcinoma (HCC). In this review, we provide an up to date overview of feasible proteome-analytical techniques for clinical questions. In addition, we present a broad summary of proteomic studies of HCC utilizing various technical approaches for the analysis of samples derived from diverse sources like HCC cell lines, animal models, human tissue and body fluids. PMID- 26357615 TI - Molecular Determinants of Prognosis in Hepatocellular Carcinoma. AB - Hepatocellular carcinoma is one of the leading causes of death by cancer worldwide. Prognosis of hepatocellular carcinoma is determined by characteristics of the tumor and the surrounding cirrhotic liver. Several molecular signatures reflecting tumor biology and derived from tumor analyses predict early tumor recurrence and survival. In contrast, molecular signatures from cirrhotic non tumor samples are enriched in immunity/inflammation related genes and could predict late tumor recurrence. Moreover, combination of clinical, pathological, and molecular features may refine prognosis prediction in these patients. Finally, molecular signatures from both tumor and non-tumor tissues will be helpful in the future to guide treatments in different clinical settings. PMID- 26357616 TI - Immune Components of Liver Damage Associated with Connective Tissue Diseases. AB - Autoimmune connective tissue diseases are associated with liver abnormalities and often have overlapping pathological and clinical manifestations. As a result, they can present great clinical challenges and evoke questions about diagnostic criteria for liver diseases. Moreover, discriminating between liver involvement as a manifestation of connective tissue disease and primary liver disease can be challenging since they share a similar immunological mechanism. Most patients with connective tissue diseases exhibit liver test abnormalities that likely result from coexisting, primary liver diseases, such as fatty liver disease, viral hepatitis, primary biliary cirrhosis, autoimmune hepatitis, and drug related liver toxicity. Liver damage can be progressive, leading to cirrhosis, complications of portal hypertension, and liver-related death, and, therefore, must be accurately identified. In this review, we highlight the challenges facing the diagnosis of liver damage associated with connective tissue disease and identify immune mechanisms involved in liver damage associated with connective tissue diseases. PMID- 26357617 TI - A Review of the Challenges Associated with the Diagnosis and Therapy of Primary Sclerosing Cholangitis. AB - Primary sclerosing cholangitis (PSC) is a chronic and progressive cholestatic liver disease that often leads to the development of cirrhosis. Complications of PSC include pruritus, fatigue, vitamin deficiencies, metabolic bone disease, dominant biliary strictures, gallstones, and hepatobiliary malignancies, most commonly cholangiocarcinoma (CCA). Despite the presumed autoimmune etiology of PSC, a clear benefit from immunosuppressive agents has not yet been established, and their use is limited by their side effects. Endoscopy is required in evaluation of biliary strictures in PSC to rule out the possibility of CCA. Liver transplantation is currently the only life-extending therapy for patients with end-stage disease. However, disease recurrence can be a source of morbidity and mortality as transplanted patients survive longer. Further studies are needed to develop an optimal therapeutic strategy for patients with PSC to decrease the incidence of complications of the disease, to decrease the need for transplantation, and to extend life expectancy. PMID- 26357618 TI - Ascitic Fluid Analysis in the Differential Diagnosis of Ascites: Focus on Cirrhotic Ascites. AB - Ascites is the pathologic accumulation of fluid within the peritoneal cavity. Because many diseases can cause ascites, in particular cirrhosis, samples of ascitic fluid are commonly analyzed in order to develop a differential diagnosis. The concept of transudate versus exudate, as determined by total protein measurements, is outdated and the use of serum-ascites albumin gradient as an indicator of portal hypertension is more accurate. Lactate dehydrogenase (LDH), vascular endothelial growth factor (VEGF), and other tumor markers can be helpful in distinguishing between malignant and benign conditions. Glucose and adenosine deaminase levels may support a diagnosis of tuberculous disease, and amylase level may indicate a diagnosis of pancreatitis. Given the specificity and sensitivity of laboratory results, accurate diagnosis should be based on both laboratory data and clinical judgment. PMID- 26357619 TI - Traditional Chinese Medicine Induced Liver Injury. AB - Traditional Chinese Medicine (TCM) is popular around the world and encompasses many different practices with particular emphasis on herbal TCM. Using the PubMed database, a literature search was undertaken to assess the extent herbal TCM products exert rare hepatotoxicity. Analysis of reported cases revealed numerous specified herbal TCM products with potential hepatotoxicity. Among these were An Shu Ling, Bai Fang, Bai Xian Pi, Ban Tu Wan, Bo He, Bo Ye Qing Niu Dan, Bofu Tsu Sho San, Boh Gol Zhee, Cang Er Zi, Chai Hu, Chaso, Chi R Yun, Chuan Lian Zi, Ci Wu Jia, Da Chai Hu Tang, Da Huang, Du Huo, Gan Cao, Ge Gen, Ho Shou Wu, Hu Bohe You, Hu Zhang, Huang Qin, Huang Yao Zi, Hwang Geun Cho, Ji Gu Cao, Ji Ji, Ji Xue Cao, Jiguja, Jin Bu Huan, Jue Ming Zi, Kamishoyosan, Kudzu, Lei Gong Teng, Long Dan Xie Gan Tang, Lu Cha, Ma Huang, Mao Guo Tian Jie Cai, Onshido, Polygonum multiflorum, Qian Li Guang, Ren Shen, Sairei To, Shan Chi, Shen Min, Shi Can, Shi Liu Pi, Shou Wu Pian, Tian Hua Fen, White flood, Wu Bei Zi, Xi Shu, Xiao Chai Hu Tang, Yin Chen Hao, Zexie, Zhen Chu Cao, and various unclassified Chinese herbal mixtures. Causality was firmly established for a number of herbal TCM products by a positive reexposure test result, the liver specific scale of CIOMS (Council for International Organizations of Medical Sciences), or both. Otherwise, the quality of case data was mixed, especially regarding analysis of the herb ingredients because of adulteration with synthetic drugs, contamination with heavy metals, and misidentification. In addition, non-herbal TCM elements derived from Agaricus blazei, Agkistrodon, Antelope, Bombyx, Carp, Fish gallbladder, Phellinus, Scolopendra, Scorpio, and Zaocys are also known or potential hepatotoxins. For some patients, the clinical course was severe, with risks for acute liver failure, liver transplantation requirement, and lethality. In conclusion, the use of few herbal TCM products may rarely be associated with hepatotoxicity in some susceptible individuals, necessitating a stringent pretreatment evaluation of the risk/benefit ratio, based on results of multicenter, randomized, double-blind, placebo-controlled clinical trials. PMID- 26357620 TI - Hepatotoxicity Secondary to Chemotherapy. AB - The difficult problem faced by multiple generation of practicing physicians is determining the cause of abnormal liver function tests in cancer patients on chemotherapy. Hepatotoxicity from chemotherapy occurs frequently from an unpredictable or idiosyncratic reaction. Despite remarkable advances in our understanding of the mechanisms of action, pharmacodynamics, and interrelationships between the liver and chemotherapy, the underlying etiology of hepatic toxicity for various agents remains unexplained. Here, we present a concise review of the broad differential diagnosis for abnormal liver function tests (LFTs) in oncology patients. PMID- 26357621 TI - Pathology of Alcoholic Liver Disease. AB - Alcohol-attributable burden on global health is increasing, and the relationship between population alcohol consumption and liver-related deaths is strong. Longstanding scientific and clinical work has led to a relatively thorough, if not complete, understanding of the effects of alcohol consumption on the liver. Pathologic features of alcoholic liver disease (ALD) are recognized by pathologists and used to assist clinicians in diagnosing and determining severity of disease in patients suspected of ALD. In this review, we discuss the pathologic manifestations of ALD and provide salient points on their pathophysiology. In addition, the benefits and indications of liver biopsy and important differential diagnoses, including features distinguishing these entities, are reviewed. PMID- 26357622 TI - Clinical Application of Transient Elastography in the Diagnosis of Liver Fibrosis: an Expert Panel Review and Opinion. AB - Liver fibrosis evaluation is pivotal for treatment decisions and prognosis assessment in patients with chronic liver disease. Liver transient elastography (TE) is a newly developed non-invasive technique for diagnosis of liver fibrosis. It can assess the state of liver fibrosis by liver stiffness measurements, and offers better performance for the diagnosis of liver cirrhosis than serum biological markers. It has now been approved for clinical use in China. The aim of this review is to provide a guide for clinicians to apply this technique appropriately. The recommendations are made under the auspices of China Foundation for Hepatitis Prevention and Control, and have been prepared by a panel experts, who have reviewed and summarized the clinical studies on TE in order to develop these recommendations. PMID- 26357623 TI - Management of Hepatitis C Before and After Liver Transplantation in the Era of Rapidly Evolving Therapeutic Advances. AB - Management of hepatitis C (HCV) in liver transplantation (LT) population presents unique challenges. Suboptimal graft survival in HCV+ LT recipients is attributable to universal HCV recurrence following LT. Although eradication of HCV prior to LT is ideal for the prevention of HCV recurrence it is often limited by adverse events, particularly in patients with advanced cirrhosis. Antiviral therapy in LT candidates needs careful monitoring, and prophylaxis with HCV antibodies is ineffective. Early antiviral therapy after LT has been investigated, but no clear benefit has been demonstrated. Protocol liver biopsy is generally recommended in HCV+ LT recipients, and antiviral therapy can be considered in those with severe/progressive HCV recurrence. Sustained virological response (SVR) can be achieved in approximately 30% of LT recipients with pegylated interferon/ribavirin (PEG-IFN/RBV) with survival benefit, but adverse effects are common. Favorable patient characteristics for response to therapy include non-1 genotype, previously untreated, low baseline HCV-RNA, and donor IL28B genotype CC. Direct acting antiviral (DAA)-based triple therapy is associated with higher rates of SVR, but with similar or slightly higher rates of side effects, and immunosuppressive regimens need to be closely monitored and adjusted during the treatment period. Notably, the safety and efficacy of HCV treatment are very likely to improve with newer generation DAA. The benefit of immunosuppressive strategy on the natural history HCV recurrence has not been well elucidated. Based upon available evidence, cyclosporine A (CSA), mycophenolate mofetil (MMF), and sirolimus appear to have a neutral or small beneficial impact on HCV recurrence. Donor interleukin 28 B (IL28B) polymorphisms appear to impact the course and treatment outcomes in recurrent HCV. Retransplantation should be considered for patients with reasonable survival probability. PMID- 26357624 TI - MicroRNAs in Drug-induced Liver Injury. AB - Drug-induced liver injury (DILI) is a leading cause of acute liver failure, and a major reason for the recall of marketed drugs. Detection of potential liver injury is a challenge for clinical management and preclinical drug safety studies, as well as a great obstacle to the development of new, effective and safe drugs. Currently, serum levels of alanine and aspartate aminotransferases are the gold standard for evaluating liver injury. However, these levels are assessed by nonspecific, insensitive, and non-predictive tests, and often result in false-positive results. Therefore, there is an urgent need for better DILI biomarkers to guide risk assessment and patient management. The discovery of microRNAs (miRNAs) as a new class of gene expression regulators has triggered an explosion of research, particularly on the measurement of miRNAs in various body fluids as biomarkers for many human diseases. The properties of miRNA-based biomarkers, such as tissue specificity and high stability and sensitivity, suggest they could be used as novel, minimally invasive and stable DILI biomarkers. In the current review, we summarize recent progress concerning the role of miRNAs in diagnosing and monitoring both clinical and preclinical DILI, and discuss the main advantages and challenges of miRNAs as novel DILI biomarkers. PMID- 26357625 TI - Hepatocellular Carcinoma and Liver Transplantation: State of the Art. AB - Hepatocellular carcinoma (HCC) is an aggressive tumor that often occurs in chronic liver disease and cirrhosis. The incidence of HCC is growing worldwide. With respect to any other available treatment for liver cancer, liver transplantation (LT) has the highest potential to cure. LT allows for removal at once of both the tumor ("seed") and the damaged-hepatic tissue ("soil") where cancerogenesis and chronic liver disorders have progressed together. The Milan criteria (MC) have been applied worldwide to select patients with HCC for LT, yielding a 4-year survival rate of 75%. These criteria represent the benchmark for patient selection and are the basis for comparison with any other suggested criteria. However, MC are often considered to be too restrictive, and recent data show that between 25% and 50% of patients with HCC are currently transplanted beyond conventional indications. Consequently, any unrestricted expansion of selection criteria will increase the need for donor organs, lengthen waiting periods, increase drop-out rates, and impair outcomes on intention-to-treat analysis. Management of HCC recurrence after LT is challenging. There are a few reports available regarding the safety and efficacy of sorafenib for HCC recurrence after LT, but the data are heterogeneous. A multi-center prospective randomized controlled trial comparing placebo with sorafenib is advised. Alternatively, a meta-analysis of patient survival with sorafenib for HCC recurrence after LT could be helpful to characterize the therapeutic benefit and safety of sorafenib. Here, we review the use of LT for HCC, with particular emphasis on the selection criteria for transplantation in patients with HCC and management of HCC recurrence after LT. PMID- 26357627 TI - Hepatobiliary Schistosomiasis. AB - Schistosomiasis is an ancient parasitic disease that has afflicted Egyptians since the time of the pharaohs. The disease is caused by lodged schistosome eggs in the host liver, evoking an immune response and leading in some patients to the development of hepatic granuloma and fibrosis. Here, we review the epidemiology, immunopathogenesis, and clinical profile of schistosomiasis. This information may aid in the development of more efficacious treatments and improved disease prognosis. PMID- 26357626 TI - The Molecular and Structural Basis of HBV-resistance to Nucleos(t)ide Analogs. AB - Infection with hepatitis B virus (HBV) is a worldwide health problem. Chronic hepatitis B can lead to fibrosis, liver cirrhosis, and hepatocellular carcinoma (HCC). Management of the latter two conditions often requires liver transplantation. Treatment with conventional interferon or pegylated interferon alpha can clear the virus, but the rates are very low. The likelihood, however, of viral resistance to interferon is minimal. The main problems with this therapy are the frequency and severity of side effects. In contrast, nucleos(t)ide analogs (NAs) have significantly lower side effects, but require long term treatment as sustained virological response rates are extremely low. However, long term treatment with NAs increases the risk for the development of anti-viral drug resistance. Only by understanding the molecular basis of resistance and using agents with multiple sites of action can drugs be designed to optimally prevent the occurrence of HBV antiviral resistance. PMID- 26357628 TI - Clinical Advances in Fibrosis Progression of Chronic Hepatitis B and C. AB - Chronic liver diseases, such as chronic hepatitis B (CHB) and chronic hepatitis C (CHC), are characterized by the presence of liver fibrosis, which may ultimately lead to cirrhosis. The progression of fibrosis is associated with various factors. Here, we review recent advances in the study of factors related to the progression rate of CHB- and CHC-induced fibrosis. Identification of these factors and establishment of a scoring system for cirrhosis risk are particularly important for predicting cirrhosis development, planning individualized treatment, and preventing fibrosis progression. PMID- 26357629 TI - Thrombosis Associated with Viral Hepatitis. AB - Viral hepatitis may promote the development of venous thromboembolism (VTE) and, more specifically, portal vein thrombosis (PVT). In this narrative review, we summarize the clinical data and discuss the possible pathogenetic roles of cytomegalovirus (CMV), Epstein-Barr virus (EBV), and hepatitis A, B, and C viruses (HAV, HBV, HCV) in the occurrence of VTE. CMV is the first qualified candidate to enter the list of VTE minor risk factors, and in the rare case of fulminant infection, both EBV and CMV, like any severe infection or inflammatory disease, increase risk for thrombosis. In chronic hepatitis B and C, it remains controversial whether antiphospholipid antibodies are important for thrombotic complications or merely an epiphenomenon. Retinal vein occlusion described in chronic hepatitis C is usually attributed to the treatment with interferon. Eltrombopag, used for HCV-related thrombocytopenia, has been associated with increased thrombotic risk. The imbalance between procoagulant and anticoagulant factors associated with chronic liver disease may have clinical implications. This may help to explain why these patients are not protected from clinical events such as VTE, PVT, and the progression of liver fibrosis. PMID- 26357632 TI - Sofosbuvir, a Significant Paradigm Change in HCV Treatment. AB - Nucleotide compounds like sofosbuvir, acyclovir, and tenofovir have proven to be amongst the most potent orally available antiviral treatments. These drugs exhibit high efficacy and a wide therapeutic index, with demonstrated utility in a number of chronic viral infections. The approval of SovaldiTM, brand name for sofosbuvir, by the U.S. Food and Drug Administration heralded improvements in chronic hepatitis C virus (HCV) treatment. Sofosbuvir was originally discovered by Pharmasset Corporation and named PSI-7977. It was subsequently acquired and advanced through phase 3 development by Gilead Sciences, Inc. In Sofosbuvir both a unique pharmacology and a high specificity for the HCV ribonucleic acid polymerase are present in a molecule that is well tolerated and highly efficacious. Phase 2 and 3 clinical trials have consistently demonstrated durable and high rates of sustained virologic response (SVR), curing patients in excess of 80% in all genotypes and >90% in treatment-naive subjects being administered combination therapy with other agents. Harvoni((r)) is the combination of sofosbuvir and the NS5A inhibitor ledipasvir in a fixed-dose oral tablet, and it has demonstrated high SVR rates in patients infected with HCV genotype 1, without the need for exogenous interferon and/or ribavirin. Here, we discuss the discovery, development, pharmacologic characterization, and results from the phase 3 trials of sofosbuvir. Hepatitis C is a chronic disease, for which most patients have been undiagnosed, are unwilling to start treatment, or are ineligible for treatment because of the high toxicity and low efficacy of interferon and ribavirin-based therapy. Clinical studies with sofosbuvir have demonstrated significant improvement over the prior standard of care, thus ushering in a new paradigm of HCV treatment and an update of treatment guidelines. PMID- 26357631 TI - Acute Hepatic Porphyria. AB - The porphyrias comprise a set of diseases, each representing an individual defect in one of the eight enzymes mediating the pathway of heme synthesis. The diseases are genetically distinct but have in common the overproduction of heme precursors. In the case of the acute (neurologic) porphyrias, the cause of symptoms appears to be overproduction of a neurotoxic precursor. For the cutaneous porphyrias, it is photosensitizing porphyrins. Some types have both acute and cutaneous manifestations. The clinical presentation of acute porphyria consists of abdominal pain, nausea, and occasionally seizures. Only a small minority of those who carry a mutation for acute porphyria have pain attacks. The triggers for an acute attack encompass certain medications and severely decreased caloric intake. The propensity of females to acute attacks has been linked to internal changes in ovarian physiology. Symptoms are accompanied by large increases in delta-aminolevulinic acid and porphobilinogen in plasma and urine. Treatment of an acute attack centers initially on pain relief and elimination of inducing factors such as medications; glucose is administered to reverse the fasting state. The only specific treatment is administration of intravenous hemin. An important goal of treatment is preventing progression of the symptoms to a neurological crisis. Patients who progress despite hemin administration have undergone liver transplantation with complete resolution of symptoms. A current issue is the unavailability of a rapid test for urine porphobilinogen in the urgent-care setting. PMID- 26357630 TI - Primary Biliary Cirrhosis and Primary Sclerosing Cholangitis: a Review Featuring a Women's Health Perspective. AB - Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are two major types of chronic cholestatic liver disease. Each disorder has distinguishing features and variable progression, but both may ultimately result in cirrhosis and hepatic failure. The following offers a review of PBC and PSC, beginning with a general overview of disease etiology, pathogenesis, diagnosis, clinical features, natural course, and treatment. In addition to commonly associated manifestations of fatigue, pruritus, and fat-soluble vitamin deficiency, select disease-related topics pertaining to women's health are discussed including metabolic bone disease, hyperlipidemia and cardiovascular risk, and pregnancy-related issues influencing maternal disease course and birth outcomes. This comprehensive review of PBC and PSC highlights some unique clinical considerations in the care of female patients with cholestatic liver disease. PMID- 26357633 TI - Chronic Hepatitis C Infection in Children: Current Treatment and New Therapies. AB - Viral hepatitis C is responsible for a large burden of disease worldwide. Treatment of hepatitis C infection is currently undergoing a revolution with the development of new direct acting antivirals that offer higher cure rates and fewer side effects than other medications currently available. Treatment options for children, although well-defined and evidence-based, are limited relative to adults as there are few trials regarding the use of these newly developed agents in children. With so much optimism in the development of novel therapeutic options for hepatitis C, it is timely to review and summarize the current standard of care treatment and indications for treatment of chronic hepatitis C in children. We provide here an overview of recent drug developments and their potential for use in children. PMID- 26357634 TI - Update on Autoimmune Hepatitis. AB - Autoimmune hepatitis (AIH), a liver disorder affecting both children and adults, is characterized by inflammatory liver histology, elevated transaminase levels, circulating nonorganspecific autoantibodies, and increased levels of immunoglobulin G, in the absence of a known etiology. Two types of AIH are recognized according to seropositivity: smooth muscle antibody and/or antinuclear antibody define AIH type 1 and antibodies to liver-kidney microsome type 1 and/or liver cytosol type 1 define AIH type 2. AIH type 1 affects both adults and children, while AIH type 2 is mainly a paediatric disease, though it does occasionally affects young adults. AIH should be considered during the diagnostic workup of any patient with increased liver enzyme levels. AIH is exquisitely responsive to immunosuppressive treatment with prednisolone with or without azathioprine, with symptom free long-term survival for the majority of patients. For those who do not respond to standard treatment, or who are difficult-to treat, mycophenolate mofetil and, in the absence of a response, calcineurin inhibitors should be tried in addition to steroids. The pathogenesis of AIH is not fully understood, although there is mounting evidence that genetic susceptibility, molecular mimicry and impaired immunoregulatory networks contribute to the initiation and perpetuation of the autoimmune attack. Liver damage is thought to be mediated primarily by CD4 T-cells, although recent studies support the involvement of diverse populations, including Th17 cells. A deeper understanding of the pathogenesis of AIH is likely to contribute to the development of novel treatments, such as the adoptive transfer of autologous expanded antigenspecific regulatory T-cells, which ultimately aim at restoring tolerance to liver-derived antigens. PMID- 26357635 TI - Animal Models for Fibrotic Liver Diseases: What We Have, What We Need, and What Is under Development. AB - Liver fibrosis is part of the wound-healing response to liver damage of various origins and represents a major health problem. Although our understanding of the pathogenesis of liver fibrosis has grown considerably over the last 20 years, effective antifibrotic therapies are still lacking. The use of animal models is crucial for determining mechanisms underlying initiation, progression, and resolution of fibrosis and for developing novel therapies. To date, no animal model can recapitulate all the hepatic and extra-hepatic features of liver disease. In this review, we will discuss the current rodent models of liver injuries. We will then focus on the available ways to target specifically particular compounds of fibrogenesis and on the new models of liver diseases like the humanized liver mouse model. PMID- 26357636 TI - An Update to Hepatobiliary Stents. AB - Endoscopic stent placement is a common primary management therapy for benign and malignant biliary strictures. However, continuous use of stents is limited by occlusion and migration. Stent technology has evolved significantly over the past two decades to reduce these problems. The purpose of this article is to review current guidelines in managing malignant and benign biliary obstructions, current endoscopic techniques for stent placement, and emerging stent technology. What began as a simple plastic stent technology has evolved significantly to include uncovered, partially covered, and fully covered self-expanding metal stents (SEMS) as well as magnetic, bioabsorbable, drug-eluting, and antireflux stents.(1). PMID- 26357637 TI - Nonalcoholic Fatty Liver Disease: Dyslipidemia, Risk for Cardiovascular Complications, and Treatment Strategy. AB - Studies have shown that nonalcoholic fatty liver disease (NAFLD) is strongly associated with several metabolic disorders and diseases, such as obesity, type 2 diabetes mellitus, and dyslipidemia. In NAFLD, dyslipidemia is manifested as increased serum triglyceride and low-density lipoprotein cholesterol levels and decreased high-density lipoprotein cholesterol levels, all of which are key risk factors for cardiovascular disease (CVD). CVD is a leading cause of mortality in NAFLD patients. Thus, implementation of an aggressive therapeutic strategy for dyslipidemia with hypolipidemic agents may mitigate the risk for CVD among NAFLD patients. Here, we provide a current review of literature regarding NAFLD, with particular emphasis on dyslipidemia and available treatment options. PMID- 26357638 TI - Liver Injury from Herbal, Dietary, and Weight Loss Supplements: a Review. AB - Herbal and dietary supplement usage has increased steadily over the past several years in the United States. Among the non-bodybuilding herbal and dietary supplements, weight loss supplements were among the most common type of HDS implicated in liver injury. While drug induced liver injury is rare, its consequences are significant and on the rise. The purpose of this review is to highlight case reports of weight loss products such as Hydroxycut and OxyElite Pro as one form of HDS that have hepatotoxic potential and to characterize its clinical effects as well as pattern of liver injury. We also propose future strategies in the identification and study of potentially hepatotoxic compounds in an effort to outline a diagnostic approach for identifying any drug induced liver injury. PMID- 26357639 TI - Dermatologic Extrahepatic Manifestations of Hepatitis C. AB - Hepatitis C virus (HCV) affects millions of people worldwide, and an estimated 3.2 million people in the United States. HCV is a hepatotropic and lymphotropic virus that causes not only liver disease, but also a significant number of extrahepatic manifestations (EHMs). Up to 74% of patients affected by HCV will have HCV-related EHMs of some severity in their lifetime. The EHMs vary from simple cutaneous palpable purpura to complex lymphoproliferative disorders, including lymphomas and immune-complex deposit diseases causing local and/or systemic complications. Mixed cryoglobulinemia (MC) is manifested by multiple systemic organ involvement, mainly skin, kidney, peripheral nerves, and salivary glands, and less frequently causes widespread vasculitis and malignant lymphoma. MC affects up to 3% of HCV-infected patients with cryoglobulinemia of clinical significance, i.e. >6%. Severe disease requires immunosuppressive or plasma exchange therapy. HCV prevalence in the United States in patients with porphyria cutanea tarda (PCT) was reported to be 66%, much higher than that in general population. Therefore, all patients with PCT should be screened for HCV. The skin rash of PCT varies from large blisters to small vesicles and/or milia on the hands. Skin manifestations due to PCT usually respond to anti-HCV treatment together with reducing skin sun exposure, avoiding triggers, having routine phlebotomy (especially for people with chronic iron overload states), and using chloroquine. Lichen planus (LP), which typically affects both the skin and oral mucosa is a chronic inflammatory disease of squamous cell origin affecting about 1% of the worldwide population. The prevalence of HCV in patients with LP varies based on geographic location. We review here the basic pathophysiology, clinical features, and management of dermatologic manifestations of HCV. PMID- 26357640 TI - Hepatitis C Associated B-cell Non-Hodgkin Lymphoma: Clinical Features and the Role of Antiviral Therapy. AB - The link between chronic hepatitis C virus (HCV) infection and a subset of B-cell non-Hodgkin lymphomas (B-NHL) is strongly supported by epidemiological studies. Evidence demonstrating complete regression of lymphoma after antiviral treatments suggests possible chronic antigenic stimulation for the origin of B-NHL and provides evidence for a virus-mediated lymphomagenesis. B-NHL is a heterogeneous group of lymphomas with varied clinical presentation and may be indolent or aggressive. The optimal management of HCV related B-NHL is not clear. Antiviral treatment may be sufficient for low-grade lymphomas, but chemotherapy is necessary in patients with high grade lymphomas. Interferon (IFN)-based antiviral treatment regimens for HCV infection are limited by poor tolerance and suboptimal antiviral response. Recently approved novel direct acting antiviral (DAA) drugs are highly effective and safe. This has opened a new era for the treatment of HCV related B-NHL alone or in conjunction with chemotherapy. Treatment of HCV associated B-NHL should be performed in an interdisciplinary approach in close consultation with hematologist and hepatologist. In this review, we summarize data regarding clinical features and epidemiology of B-NHL and discuss novel therapeutic approaches, including DAAs, that may prove to be effective in the treatment of HCV associated lymphomas. PMID- 26357641 TI - Management of Hepatitis C Post-liver Transplantation: a Comprehensive Review. AB - Infection with hepatitis C virus (HCV) is a common cause of chronic liver disease, and HCV-related cirrhosis and hepatocellular carcinoma are the leading causes for liver transplantation in the Western world. Recurrent infection of the transplanted liver allograft is universal in patients with detectable HCV viremia at the time of transplant and can cause a spectrum of disease, ranging from asymptomatic chronic infection to an aggressive fibrosing cholestatic hepatitis. Recurrent HCV is more aggressive in the post-transplant population and is a leading cause of allograft loss, morbidity, and mortality. Historically, treatment of recurrent HCV has been limited by low rates of treatment success and high side effect profiles. Over the past few years, promising new therapies have emerged for the treatment of HCV that have high rates of sustained virological response without the need for interferon based regimens. In addition to being highly effective, these treatments have higher rates of adherence and a lower side effect profile. The purpose of this review is to summarize current therapies in recurrent HCV infection, to review the recent advances in therapy, and to highlight areas of ongoing research. PMID- 26357643 TI - The Recent Review of the Genitourinary Syndrome of Menopause. AB - The genitourinary syndrome of menopause (GSM) is a new term that describes various menopausal symptoms and signs including not only genital symptoms (dryness, burning, and irritation), and sexual symptoms (lack of lubrication, discomfort or pain, and impaired function, but also urinary symptoms (urgency, dysuria, and recurrent urinary tract infections). The terms vulvovaginal atrophy and atrophic vaginitis, which were generally used until recently, had a limitation because they did not cover the full spectrum of symptoms and did not imply that the symptoms are related to a decreased estrogen level in menopause. Since the GSM may have a profound negative impact on the quality of life of postmenopausal women, women should be made aware of these problems and treated with an appropriate effective therapy. Thus, in this review we introduce new terminology and discuss the importance of comprehension of GSM and the necessity of active treatment of this syndrome in postmenopausal women. PMID- 26357644 TI - G-protein Coupled Estrogen Receptor (GPER/GPR30) and Women's Health. AB - Estrogen - the female sexual hormone playing the most important role - plays a physiologically significant role, not only regulating in cell signals with second messenger but also being active in regulating transcription. Estrogen receptor (ER) which is a protein accepting estrogen not only play the role of a transcription factor combining with other genes to regulate their activity like other nuclear receptors but also performs external activities, combining with DNA, etc. G-protein coupled ER (GPER) that has been recently discovered exists as 7-membrane and has non-genomic (rapid) signaling. These functions, however, are not extensively addressed. This paper discusses the roles of GPER and its physiological mechanism. PMID- 26357642 TI - MicroRNAs as Important Players in Host-hepatitis B Virus Interactions. AB - Hepatitis B virus (HBV) infection, a major public health problem, causes acute and chronic hepatitis that is often complicated by liver cirrhosis and hepatocellular carcinoma. The pathogenic mechanisms of HBV-related liver disease are not well understood, and the current licensed therapies are not effective in permanently clearing virus from the circulation. In recent years, the role of micro-ribonucleic acids (miRNAs) in HBV infection has attracted great interest. Cellular miRNAs can influence HBV replication directly by binding to HBV transcripts and indirectly by targeting cellular factors relevant to the HBV life cycle. They are also involved in the regulation of cellular genes and signaling pathways that have critical roles in HBV pathogenesis. HBV infection, in turn, can trigger changes in cellular miRNA expression that are associated with distinctive miRNA expression profiles depending on the phase of liver disease. These alterations in miRNA expression have been linked to disease progression and hepatocarcinogenesis. We provide here an up to date review regarding the field of miRNAs and HBV interplay and highlight the potential utility of miRNAs as diagnostic biomarkers and therapeutic targets for the management of HBV-related liver disease. PMID- 26357645 TI - Factors Associated with Mammographic Density in Postmenopausal Women. AB - OBJECTIVES: Breast density increases the risk of breast cancer, but also in the interpretation of mammography is also important. This study examine the risk factors affecting breast density in postmenopausal women. METHODS: Between January 2013 and January 2014, 215 patients admitted to The Clinics of Gynecology and Obstetrics with complaints of menopause were taken. According to the results of mammography, Group I (non-dense, n = 175) and Group II (dense, n = 40) were created. The informations of the caseswere analyzed retrospectively. RESULTS: In Group I, body mass index (BMI), number of pregnancies, parity were significantly higher than group II (P < 0.05). In group II, the withdrawal period of menstruation and progesterone levels were significantly higher (P < 0.05). In logistic regression analysis, BMI for dense breasts and number of pregnancies were found to be an independent risk factor (P < 0.05). CONCLUSION: Increased BMI, pregnancy and parity, result of reduction in density , but longer duration of menopause and increased progesterone cause an increase in density. BMI and the number of pregnancy was found to be independent risk factors for reducing breast density. PMID- 26357646 TI - Expression of Vitamin D Receptor in Seminal Vesicles of Cholesterol Formula Mice. AB - OBJECTIVES: Genomic function of vitamin D receptor (VDR) indicates spermatogenesis that is important for in male reproductive organ authors evaluated the VDR expression in seminal vesicles with high cholesterol (HC) formula diet rat, because there is no report about relationship or difference in VDR in seminal vesicles between HC and control. METHODS: Male C57BL/6 mice aged 5 weeks were raised for 13 weeks. After one week of adaptation-period, they were fed different diet on normal AIN-93G diet, or HC diet containing 2% cholesterol for 12 weeks. The antibodies used were rabbit anti-VDR primary polyclonal. RESULTS: There was no significant difference in VDR reactivity in seminal vesicles, body weight of rat and weight of seminal vesicles between HC group and normal control group. CONCLUSION: Our data give the no difference in expression of VDR of seminal vesicles rat between HC formula diet and normal AIN-93G diet. But we confirmed the VDR expression in seminal vesicles. PMID- 26357647 TI - Effect of Glucagon-like Peptide-1 on the Differentiation of Adipose-derived Stem Cells into Osteoblasts and Adipocytes. AB - OBJECTIVES: Glucagon-like peptide-1 (GLP-1) is an intestinally secreted hormone and it plays an important role in the regulation of glucose homeostasis. However, the possible role of GLP-1 in the differentiation of adipose-derived stem cells (ADSCs) remains unknown. Therefore this study investigated the effect of GLP-1 on the differentiation of ADSCs into osteoblasts and adipocytes. METHODS: ADSCs were isolated from human adipose tissues of the abdomens, cultured and characterized by flow cytometry and multi-lineage potential assay. ADSCs were induced in osteogenic and adipogenic media treated with two different doses (10 and 100 nM) of GLP-1, and then the effect of GLP-1 on differentiation of ADSCs into osteoblast and adipocyte was examined. The signaling pathway involved in these processes was also examined. RESULTS: Isolated human ADSCs expressed mesenchymal stem cell (MSC) specific markers as well as GLP-1 receptor (GLP-1R) proteins. They also showed multiple-lineage potential of MSC. GLP-1 was upregulated the activity and mRNA expression of osteoblast-specific marker, alkaline phosphatase and the mineralization of calcium. In contrast, GLP-1 significantly suppressed the expression of adipocyte-specific markers, peroxisome proliferator-activated receptor gamma (PPAR-gamma), lipoprotein lipase (LPL) and adipocyte protein 2 (AP2). This decreased expression of adipocyte specific markers caused by GLP-1 was significantly reversed by the treatment of extracellular signal-regulated kinase (ERK) inhibitor, PD98059 (P < 0.05). CONCLUSION: This result demonstrates that GLP-1 stimulates osteoblast differentiation in ADSCs, whereas it inhibits adipocyte differentiation. The ERK signaling pathway seems to be involved in these differentiation processes mediated by GLP-1. PMID- 26357648 TI - Effects of Hormone Therapy on Serum Lipid Levels in Postmenopausal Korean Women. AB - OBJECTIVES: This study was conducted to examine the effects of hormone therapy on serum lipid levels in postmenopausal Korean women. METHODS: This retrospective cohort study included 154 healthy postmenopausal Korean women. Seventy-nine women took oral estrogen (conjugated equine estrogen 0.625 mg/day or equivalent), and 75 applied estrogen transdermally using 0.1% 17beta-estradiol gel. Micronized progesterone (MP) was added to 40 women of oral group and 49 women in transdermal group. Serum levels of triglyceride, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and lipoprotein (a) were measured before, 3 and 6 month after hormone therapy. RESULTS: At baseline, mean body mass index (BMI) were lower (22.76 vs. 23.74 kg/m(2)) and proportion of family history of cardiovascular disease (CVD) (61 vs. 39%) were higher in oral group. In oral group, LDL-C and lipoprotein(a) levels decreased, and triglyceride and HDL-C levels increased significantly after 3 and 6 months. There was no significant change in lipoprotein levels compared to the baseline in transdermal group. There were also no differences with additional MP. Changing pattern of HDL-C during 6 months was significantly different by the route of estrogen administration. CONCLUSION: Oral estrogen therapy might be more beneficial than transdermal estrogen in terms of lipid in postmenopausal Korean women. The estrogen effects are not influenced by adding MP. PMID- 26357649 TI - Preimplantation Exposure to Bisphenol A and Triclosan May Lead to Implantation Failure in Humans. AB - Endocrine disrupting chemicals (EDCs) are chemicals that have the capacity to interfere with normal endocrine systems. Two EDCs, bisphenol A (BPA) and triclosan (TCS), are mass-produced and widespread. They both have estrogenic properties and similar chemical structures and pharmacokinetic features and have been detected in human fluids and tissues. Clinical evidence has suggested a positive association between BPA exposure and implantation failure in IVF patients. Studies in mouse models have suggested that preimplantation exposure to BPA and TCS can lead to implantation failure. This paper reviews the relationship between preimplantation exposure to BPA and TCS and implantation failure and discusses the remaining problems and possible solutions. PMID- 26357650 TI - Decorin-Mediated Inhibition of Human Trophoblast Cells Proliferation, Migration, and Invasion and Promotion of Apoptosis In Vitro. AB - Preeclampsia (PE) is a unique complication of pregnancy, the pathogenesis of which has been generally accepted to be associated with the dysfunctions of extravillous trophoblast (EVT) including proliferation, apoptosis, and migration and invasion. Decorin (DCN) has been proved to be a decidua-derived TGF-binding proteoglycan, which negatively regulates proliferation, migration, and invasiveness of human extravillous trophoblast cells. In this study, we identified a higher expression level of decorin in severe PE placentas by both real-time reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). And an inhibitory effect of decorin on proliferation, migration, and invasion and an enhanced effect on apoptosis in trophoblast cells HTR-8/SVneo and JEG-3 were validated in vitro. Also the modulations of decorin on trophoblast cells' metastasis and invasion functions were detected through regulating the matrix metalloproteinases (MMP2 and MMP9). Thus, we suggested that the contribution of decorin to the modulation of trophoblast cells might have implications for the pathogenesis of preeclampsia. PMID- 26357651 TI - Antimicrobial Effects and Resistant Regulation of Magnolol and Honokiol on Methicillin-Resistant Staphylococcus aureus. AB - The antimicrobial killing activity toward methicillin-resistant Staphylococcus aureus (MRSA) has been a serious emerging global issue. In a continuing search for compounds with antibacterial activity against several microorganisms including S. aureus and MRSA, an n-hexane extract of Magnolia officinalis was found to contain magnolol. This compound exhibited potent activity against S. aureus, standard methicillin-susceptible S. aureus (MSSA), and MRSA as well as clinical MRSA isolates. When combined with oxacillin, the antibacterial activities of magnolol and honokiol against the MRSA strain were increased compared to single treatment without antibiotics at 10 ug/mL and 25 ug/mL, respectively. These activities of magnolol and honokiol were dose dependent. Also, magnolol showed synergistic effects with oxacillin against 13 clinical isolates of MRSA. It was determined that magnolol and honokiol had a synergistic effect with oxacillin against MRSA strain. Furthermore, the magnolol inhibited the expression of the resistant genes, mecA, mecI, femA, and femB, in mRNA. We concluded that the antibacterial activity of magnolol against MRSA strain is more related to the mecI's pathway and components of the cell wall than mecR1. Therefore, the results obtained in this study suggest that the combination of magnolol and antibiotics could lead to the development of new combination antibiotics against MRSA infection. PMID- 26357653 TI - MiR-183 Regulates ITGB1P Expression and Promotes Invasion of Endometrial Stromal Cells. AB - We applied in the previous study miRNA microarray screening analysis to identify several differentially expressed miRNAs, including miR-183 in normal, eutopic, and ectopic endometrium. Knockdown of miR-183 expression induced the invasiveness and inhibition of apoptosis in endometrial stromal cells. The current study aims to identify the miR-183 targets with relevance to cell functions in endometrial stromal cells, to verify the interaction of miR-183 with its target genes, and to confirm the role of miR-183 in the process of endometriosis. Using microarray analysis, we identified 27 differentially expressed genes (19 were upregulated and 8 downregulated), from which we selected 4 downregulated genes (ITGB1, AMIGO2, VAV3, and PSEN2) based on GO databases for functional analysis and significant pathway analysis. Western blotting analyses showed that integrin beta1 (ITGB1), but not AMIGO2, was affected by miR-183 overexpression, whereas no protein expression of VAV3 and PSEN2 was detected. Luciferase reporter assay verified that ITGB1 is a target gene of miR-183. Moreover, we found that ITGB1 is overexpressed in the endometrium of endometriosis patients. Furthermore, overexpression of ITGB1 rescued the repressive effects of miR-183 on the invasiveness of endometrial stromal cells. These findings, together with the fact that ITGB1 is a critical factor for cell adhesion and invasiveness, suggest that miR-183 may be involved in the development of endometriosis by regulating ITGB1 in endometrial stromal cells. PMID- 26357652 TI - Positive mRNA Translational Control in Germ Cells by Initiation Factor Selectivity. AB - Ultimately, the production of new proteins in undetermined cells pushes them to new fates. Other proteins hold a stem cell in a mode of self-renewal. In germ cells, these decision-making proteins are produced largely from translational control of preexisting mRNAs. To date, all of the regulation has been attributed to RNA binding proteins (RBPs) that repress mRNAs in many models of germ cell development (Drosophila, mouse, C. elegans, and Xenopus). In this review, we focus on the selective, positive function of translation initiation factors eIF4E and eIF4G, which recruit mRNAs to ribosomes upon derepression. Evidence now shows that the two events are not separate but rather are coordinated through composite complexes of repressors and germ cell isoforms of eIF4 factors. Strikingly, the initiation factor isoforms are themselves mRNA selective. The mRNP complexes of translation factors and RBPs are built on specific populations of mRNAs to prime them for subsequent translation initiation. Simple rearrangement of the partners causes a dormant mRNP to become synthetically active in germ cells when and where they are required to support gametogenesis. PMID- 26357654 TI - Analysis of the Influence of Hormone Replacement Therapy on Osteocalcin Gene Expression in Postmenopausal Women. AB - BACKGROUND: Osteocalcin (OC) contributes to the process of bone mineralization. Present study was designed to investigate the changes in OC gene expression of postmenopausal women treated with hormone replacement therapy (HRT). Study was also designed to evaluate OC gene expression in cells which are not part of connective tissue. MATERIAL AND METHODS: Research was carried out on 30 postmenopausal women not treated and 30 treated with HRT. Examination of OC gene expression was conducted on peripheral blood lymphocytes (PBL) and buccal epithelial lining (BEL). Densitometry was conducted on femur and mandible. RESULTS: Tests revealed OC gene expression in BEL and PBL. BMD was higher in groups treated with HRT. Assessment of correlation between the OC gene expression in BEL and BMD of mandible revealed significant positive relation. CONCLUSIONS: OC gene expression can be stated BEL and PBL. Analysis of correlation between OC gene expression in oral cavity and mandible BMD showed significant correlation between local OC expression and local bone metabolism. The relation between OC gene expression and bone metabolism is complex and further research is needed to clear all of the uncertainties. PMID- 26357655 TI - Prognostic Significance of mTOR and PTEN in Patients with Esophageal Squamous Cell Carcinoma. AB - The prognostic value of mTOR in ESCC is much controversial; this study aimed to determine the prognostic importance of mTOR and PTEN in patients with ESCC. A total of 148 consecutive patients who underwent esophagectomy from 2010 to 2012 were included in this study, tested by western bolt and immunohistochemistry for mTOR and PTEN expression. Correlation coefficient was calculated using Pearson's correlation test. The 3-year overall survival (OS) and disease-free survival (DFS) were calculated in relation to the two markers. 94 (63.5%) of 148 were mTOR high expression, and PTEN high expression was detected in 46 (31.1%) of the 148 patients with ESCC. The Pearson correlation coefficient revealed a significant negative correlation in two proteins (correlation coefficient = -0.189, P < 0.005). The 3-year OS and DFS time in the mTOR-high group was 23.9 and 18.4 months, respectively, and the time in the mTOR-low group was 33.9 months and 31.4 months, respectively. The difference of survival rate between the two groups remained statistically significant. mTOR-low or PTEN-high patients had better 3 year rates of OS and DFS than mTOR-high or PTEN-low group (P < 0.001 by the log rank test). This study also found that mTOR was an independence prognostic factor by multivariate analysis. PMID- 26357656 TI - The Effect of MGCD0103 on CYP450 Isoforms Activity of Rats by Cocktail Method. AB - MGCD0103, an isotype-selective histone deacetylase inhibitor (HDACi), has been clinically evaluated for the treatment of hematologic malignancies and advanced solid tumors, alone and in combination with standard-of-care agents. In order to investigate the effects of MGCD0103 on the metabolic capacity of cytochrome P450 (CYP) enzymes, a cocktail method was employed to evaluate the activities of human CYP2B1, CYP1A2, CYP2C11, CYP2D6, CYP3A4, and CYP2C9. The rats were randomly divided into MGCD0103 group (Low, Medium, and High) and control group. The MGCD0103 group rats were given 20, 40, and 80 mg/kg (Low, Medium, and High) MGCD0103 by continuous intragastric administration for 7 days. Six probe drugs, bupropion, phenacetin, tolbutamide, metoprolol, testosterone, and omeprazole, were given to rats through intragastric administration, and the plasma concentrations were determined by UPLC-MS/MS. Statistical pharmacokinetics difference for tolbutamide in rats were observed by comparing MGCD0103 group with control group. Continuous 7-day intragastric administration of MGCD0103 slightly induces the activities of CYP2C11 of rats. PMID- 26357658 TI - The Application of Fluorescence Optical Imaging in Systemic Sclerosis. AB - OBJECTIVE: The aim of this study was to visualize soft tissue inflammation using FOI on patients with Systemic Sclerosis (SSc) characterized by SSc-related Raynaud's phenomenon and to detect the therapeutic response to treatment with iloprost or alprostadil. METHODS: Twenty-one patients with SSc and Raynaud's phenomenon and twenty-six healthy controls were prospectively included. The SSc patients were intravenously treated with iloprost or alprostadil over seven days. FOI was performed at baseline and after seven days using an intravenous application of indocyanine green (ICG). The hands were divided into nineteen segments per hand. All segments were quantitatively evaluated to determine changes in ICG. RESULTS: The sensitivity and specificity of FOI in the detection of ICG enhancement in patients with SSc were 95% versus 96%. At baseline, 31.5% hand segments showed ICG enhancement. After seven days of either iloprost or alprostadil therapy a significant reduction in the ICG was observed which ranged from 40.9% to 24.7%. CONCLUSION: The study demonstrates that the FOI technique is able to visualize soft-tissue inflammation with both high sensitivity and specificity. The anti-inflammatory therapeutic effects of iloprost were slightly stronger than alprostadil. FOI offers promising benefits in the diagnosis and therapy of patients with SSc-associated Raynaud's phenomenon. PMID- 26357657 TI - BRCA1 185delAG Mutation Enhances Interleukin-1beta Expression in Ovarian Surface Epithelial Cells. AB - Familial history remains the strongest risk factor for developing ovarian cancer (OC) and is associated with germline BRCA1 mutations, such as the 185delAG founder mutation. We sought to determine whether normal human ovarian surface epithelial (OSE) cells expressing the BRCA1 185delAG mutant, BRAT, could promote an inflammatory phenotype by investigating its impact on expression of the proinflammatory cytokine, Interleukin-1beta (IL-1beta). Cultured OSE cells with and without BRAT were analyzed for differential target gene expression by real time PCR, western blot, ELISA, luciferase reporter, and siRNA assays. We found that BRAT cells expressed increased cellular and secreted levels of active IL 1beta. BRAT-expressing OSE cells exhibited 3-fold enhanced IL-1beta mRNA expression, transcriptionally regulated, in part, through CREB sites within the ( 1800) to (-900) region of its promoter. In addition to transcriptional regulation, BRAT-mediated IL-1beta expression appears dualistic through enhanced inflammasome-mediated caspase-1 cleavage and activation of IL-1beta. Further investigation is warranted to elucidate the molecular mechanism(s) of BRAT mediated IL-1beta expression since increased IL-1beta expression may represent an early step contributing to OC. PMID- 26357659 TI - The Content of the 14 Metals in Cancellous and Cortical Bone of the Hip Joint Affected by Osteoarthritis. AB - The aim of the study was to determine the content of particular elements Ca, Mg, P, Na, K, Zn, Cu, Fe, Mo, Cr, Ni, Ba, Sr, and Pb in the proximal femur bone tissue (cancellous and cortical bone) of 96 patients undergoing total hip replacement for osteoarthritis using ICP-AES and FAAS analytical techniques. The interdependencies among these elements and their correlations depended on factors including age, gender, place of residence, tobacco consumption, alcohol consumption, exposure to environmental pollution, physical activity, and type of degenerative change which were examined by statistical and chemometric methods. The factors that exerted the greatest influence on the elements in the femoral head and neck were tobacco smoking (higher Cr and Ni content in smokers), alcohol consumption (higher concentrations of Ni, Cu in people who consume alcohol), and gender (higher Cu, Zn, and Ni concentrations in men). The factors influencing Pb accumulation in bone tissue were tobacco, alcohol, gender, and age. In primary and secondary osteoarthritis of the hip, the content and interactions of elements are different (mainly those of Fe and Pb). There were no significant differences in the concentrations of elements in the femoral head and neck that could be attributed to residence or physical activity. PMID- 26357660 TI - Effect of the Common Fat Mass and Obesity Associated Gene Variants on Obesity in Pakistani Population: A Case-Control Study. AB - BACKGROUND/OBJECTIVE: Obesity has become a global epidemic due to an increase in the number of obese individuals worldwide. There is little research in the field of obesity genetics in Pakistan. The aim of the current study was to analyze the association of common variants in Fat Mass and Obesity associated (FTO) gene with obesity in Pakistan, to find out the effect of the selected SNPs on anthropometric and biochemical traits, and to observe whether these variants act synergistically. METHODS: Samples from 631 subjects were taken after informed consent and were used for serum parameters and genetic analysis. Lipid profile was determined, tetra-ARMS PCR was used for genotyping, and allele/genotype frequencies and genescore were calculated. RESULTS: All FTO variants were associated with obesity, and some biochemical and anthropometric measures and had higher minor allele frequencies than those reported for Asian populations previously. The risk allele of each single nucleotide polymorphism resulted in an increase in BMI in a quantitative manner. CONCLUSION: Common forms of obesity are due to a combined net effect of many variants presented in same or different genes. The more the number of risk alleles present, the higher the risk and severity of obesity resulting from an increase in BMI. PMID- 26357661 TI - Paracrine Regulation of Steroidogenesis in Theca Cells by Granulosa Cells Derived from Mouse Preantral Follicles. AB - Interaction partners of follicular cells play a significant role in steroidogenesis, follicular formation, and development. Androgen secreted by theca cells (TCs) can initiate follicle development and ovulation and provide precursor materials for estrogen synthesis. Therefore, studies on ovarian microenvironment will not only lead to better understanding of the steroidogenesis but also have clinical significance for ovarian endocrine abnormalities such as hyperandrogenism in polycystic ovary syndrome (PCOS). This study applied the Transwell coculture model to investigate if the interaction between granulosa and theca cells may affect androgen production in theca cells. Concentrations of testosterone and androstenedione in the spent medium were measured by radioimmunoassay and enzyme linked immunosorbent assay, respectively. The results show that the coculture with granulosa cells (GCs) increases steroidogenesis in TCs. In addition, testosterone and androstenedione productions in response to LH stimulation were also increased in the coculture model. Significantly increased mRNA expressions of steroidogenic enzymes (Star, Cyp11a1, Cyp17a1, and Hsd3b2) were observed in the cocultured TCs. Thus, GCs were capable of promoting steroidogenesis and LH responsiveness in TCs. This study provided a basis for further exploration of ovarian endocrine mechanism and pathologies. PMID- 26357662 TI - Evaluation of Antileishmanial Activity of Albaha Medicinal Plants against Leishmania amazonensis. AB - Sixteen methanolic extracts obtained from thirteen plant species, selected either from ethnobotanical or chemotaxonomical data, were screened for their antileishmanial activity against Leishmania amazonensis. The cytotoxic activity against normal peritoneal macrophages from normal BALB/c mice was also determined. Eight extracts had IC50 values ranging from <12.5 to 37.8 ug/mL against promastigotes. Achillea biebersteinii flower, Euphorbia helioscopia, and Solanum incanum leaf extracts showed antileishmanial activities with IC50 between <12.5-26.9 ug/mL and acceptable selectivity indices of 8-5. The other leishmanicidal plant extracts, with IC50 ranging from 18.0 to 29.5 ug/mL, exhibited low selectivity indices. PMID- 26357663 TI - Increased Oxidation as an Additional Mechanism Underlying Reduced Clot Permeability and Impaired Fibrinolysis in Type 2 Diabetes. AB - AIMS: We sought to investigate whether enhanced oxidation contributes to unfavorable fibrin clot properties in patients with diabetes. METHODS: We assessed plasma fibrin clot permeation (K s , a measure of the pore size in fibrin networks) and clot lysis time induced by recombinant tissue plasminogen activator (CLT) in 163 consecutive type 2 diabetic patients (92 men and 71 women) aged 65 +/- 8.8 years with a mean glycated hemoglobin (HbA1c) of 6.8%. We also measured oxidative stress markers, including nitrotyrosine, the soluble form of receptor for advanced glycation end products (sRAGE), 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha ), oxidized low-density lipoprotein (oxLDL), and advanced glycation end products (AGE). RESULTS: There were inverse correlations between K s and nitrotyrosine, sRAGE, 8-iso-PGF2alpha , and oxLDL. CLT showed a positive correlation with oxLDL and nitrotyrosine but not with other oxidation markers. All these associations remained significant for K s after adjustment for fibrinogen, disease duration, and HbA1c (all P < 0.05), while oxLDL was the only independent predictor of CLT. CONCLUSIONS: Our study shows that enhanced oxidative stress adversely affects plasma fibrin clot properties in type 2 diabetic patients, regardless of disease duration and glycemia control. PMID- 26357665 TI - A Digital Architecture for a Network-Based Learning Health System: Integrating Chronic Care Management, Quality Improvement, and Research. AB - INTRODUCTION: We collaborated with the ImproveCareNow Network to create a proof of-concept architecture for a network-based Learning Health System. This collaboration involved transitioning an existing registry to one that is linked to the electronic health record (EHR), enabling a "data in once" strategy. We sought to automate a series of reports that support care improvement while also demonstrating the use of observational registry data for comparative effectiveness research. DESCRIPTION OF ARCHITECTURE: We worked with three leading EHR vendors to create EHR-based data collection forms. We automated many of ImproveCareNow's analytic reports and developed an application for storing protected health information and tracking patient consent. Finally, we deployed a cohort identification tool to support feasibility studies and hypothesis generation. There is ongoing uptake of the system. To date, 31 centers have adopted the EHR-based forms and 21 centers are uploading data to the registry. Usage of the automated reports remains high and investigators have used the cohort identification tools to respond to several clinical trial requests. SUGGESTIONS FOR FUTURE USE: The current process for creating EHR-based data collection forms requires groups to work individually with each vendor. A vendor agnostic model would allow for more rapid uptake. We believe that interfacing network-based registries with the EHR would allow them to serve as a source of decision support. Additional standards are needed in order for this vision to be achieved, however. CONCLUSIONS: We have successfully implemented a proof-of concept Learning Health System while providing a foundation on which others can build. We have also highlighted opportunities where sponsors could help accelerate progress. PMID- 26357664 TI - Psoriasis and Diabetes: A Multicenter Study in 222078 Type 2 Diabetes Patients Reveals High Levels of Depression. AB - OBJECTIVE: This study aimed to investigate the association between psoriasis and disease outcome in type 2 diabetes (T2D). METHODS: 222078 T2D patients (>=10 years old) from the prospective, multicenter diabetes patient registry were analyzed. Specific search items were used to identify psoriasis patients. Multiple regression models were fitted and adjusted for demographic confounder. RESULTS: 232 T2D patients had comorbid psoriasis. After adjusting psoriasis patients revealed a higher BMI (31.8 [31.0; 32.6] versus 30.6 [30.5; 30.6] kg/m2, p = 0.004) and HbA1c (64.8 [62.1; 67.6] versus 59.0 [58.9; 59.1] mmol/mol, p < 0.0001). Insulin was used more frequently (62.3 [55.7; 68.5] versus 50.9 [50.7; 51.1] %, p = 0.001), only OAD/GLP-1 was similar, and nonpharmacological treatment was less common (13.3 [9.5; 18.3] versus 21.9 [21.7; 22.1] %, p = 0.002). Severe hypoglycemia (0.31 [0.238; 0.399] versus 0.06 [0.057; 0.060] events per patient year, p < 0.0001), hypertension (86.1 [81.1; 90.0] versus 68.0 [67.8; 68.2] %, p < 0.0001), and thyroid disease (14.0 [10.1; 19.2] versus 4.6 [4.5; 4.7] %, p < 0.0001) were more prevalent. Depression occurred more often (10.5 [7.1; 15.2] versus 2.8 [2.7; 2.8] %, p < 0.0001). CONCLUSIONS: Clinical diabetes characteristics in psoriasis T2D patients were clearly worse compared to patients without psoriasis. Comorbid conditions and depression were more prevalent, and more intensive diabetes therapy was required. PMID- 26357667 TI - Analysis of Hybrid Buffering and Retransmission in OBS Networks. AB - Burst contention is a major problem in the Optical Burst Switching (OBS) networks. Due to inadequate contention resolution techniques, the burst loss is prominent in OBS. In order to resolve contention fiber delay lines, wavelength converters, deflection routing, burst segmentation, and retransmission are used. Each one has its own limitations. In this paper, a new hybrid scheme is proposed which combines buffering and retransmission, which increases the mean number of bursts processed in the system. In this hybrid method, retransmission with controllable arrival and uncontrollable arrival is analyzed. Normally all the bursts reach the first hop and few of them go for second hop to reach destination. After all the bursts reach the destination the server may go for maintenance activity or wait for the arrival of next burst. We model it as a batch arrival single server retrial queue with buffer. Numerical results are analyzed to show the mean number of bursts processed in the system with uncontrollable arrival and controllable arrivals. PMID- 26357666 TI - Population-Based Surveillance of Neisseria meningitidis Antimicrobial Resistance in the United States. AB - Background. Antimicrobial treatment and chemoprophylaxis of patients and their close contacts is critical to reduce the morbidity and mortality and prevent secondary cases of meningococcal disease. Through the 1990's, the prevalence of antimicrobial resistance to commonly used antimicrobials among Neisseria meningitidis was low in the United States. Susceptibility testing was performed to ascertain whether the proportions of isolates with reduced susceptibility to antimicrobials commonly used for N meningitidis have increased since 2004 in the United States. Methods. Antimicrobial susceptibility testing was performed by broth microdilution on 466 isolates of N meningitidis collected in 2004, 2008, 2010, and 2011 from an active, population-based surveillance system for susceptibility to ceftriaxone, ciprofloxacin, penicillin G, rifampin, and azithromycin. The molecular mechanism of reduced susceptibility was investigated for isolates with intermediate or resistant phenotypes. Results. All isolates were susceptible to ceftriaxone and azithromycin, 10.3% were penicillin G intermediate (range, 8% in 2008-16.7% in 2010), and <1% were ciprofloxacin, rifampin, or penicillin G resistant. Of the penicillin G intermediate or resistant isolates, 63% contained mutations in the penA gene associated with reduced susceptibility to penicillin G. All ciprofloxacin-resistant isolates contained mutations in the gyrA gene associated with reduced susceptibility. Conclusions. Resistance of N meningitidis to antimicrobials used for empirical treatment of meningitis in the United States has not been detected, and resistance to penicillin G and chemoprophylaxis agents remains uncommon. Therapeutic agent recommendations remain valid. Although periodic surveillance is warranted to monitor trends in susceptibility, routine clinical testing may be of little use. PMID- 26357668 TI - A Dynamic Intrusion Detection System Based on Multivariate Hotelling's T2 Statistics Approach for Network Environments. AB - The ever expanding communication requirements in today's world demand extensive and efficient network systems with equally efficient and reliable security features integrated for safe, confident, and secured communication and data transfer. Providing effective security protocols for any network environment, therefore, assumes paramount importance. Attempts are made continuously for designing more efficient and dynamic network intrusion detection models. In this work, an approach based on Hotelling's T(2) method, a multivariate statistical analysis technique, has been employed for intrusion detection, especially in network environments. Components such as preprocessing, multivariate statistical analysis, and attack detection have been incorporated in developing the multivariate Hotelling's T(2) statistical model and necessary profiles have been generated based on the T-square distance metrics. With a threshold range obtained using the central limit theorem, observed traffic profiles have been classified either as normal or attack types. Performance of the model, as evaluated through validation and testing using KDD Cup'99 dataset, has shown very high detection rates for all classes with low false alarm rates. Accuracy of the model presented in this work, in comparison with the existing models, has been found to be much better. PMID- 26357669 TI - Audit of Orthopaedic Surgical Documentation. AB - Introduction. The Royal College of Surgeons in England published guidelines in 2008 outlining the information that should be documented at each surgery. St. James's Hospital uses a standard operation sheet for all surgical procedures and these were examined to assess documentation standards. Objectives. To retrospectively audit the hand written orthopaedic operative notes according to established guidelines. Methods. A total of 63 operation notes over seven months were audited in terms of date and time of surgery, surgeon, procedure, elective or emergency indication, operative diagnosis, incision details, signature, closure details, tourniquet time, postop instructions, complications, prosthesis, and serial numbers. Results. A consultant performed 71.4% of procedures; however, 85.7% of the operative notes were written by the registrar. The date and time of surgery, name of surgeon, procedure name, and signature were documented in all cases. The operative diagnosis and postoperative instructions were frequently not documented in the designated location. Incision details were included in 81.7% and prosthesis details in only 30% while the tourniquet time was not documented in any. Conclusion. Completion and documentation of operative procedures were excellent in some areas; improvement is needed in documenting tourniquet time, prosthesis and incision details, and the location of operative diagnosis and postoperative instructions. PMID- 26357670 TI - The short-term and long-term outcomes of the endoscopic resection for the superficial pharyngeal squamous cell carcinoma. AB - BACKGROUND AND STUDY AIMS: Early detection of superficial pharyngeal squamous cell carcinoma (SPSCC) using narrow-band imaging as well as the increasing use of ER for gastrointestinal cancers may increase the number of ER for SPSCC. The aims of this study were to clarify the feasibility of ER for SPSCC and its long-term outcomes. PATIENTS AND METHODS: In total, 84 patients with 115 lesions were treated by endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) between March 2004 and August 2012. We retrospectively assessed the en bloc and R0 resection rates, complications, lymph node metastasis (LNM), local recurrence, metachronous pharyngeal and esophageal SCC, 5-year overall and cause specific survival rates. RESULTS: Higher proportions of en bloc and R0 resection were achieved with ESD compared to EMR (en bloc 100 % vs. 60 %, P < 0.001; R0 59 % vs. 26 %, P < 0.005). There were no significant complications in both groups. None of the patients died from primary SPSCC during the median follow-up of 34 months (range, 3 - 115). LNM occurred in three patients and local recurrence was detected in seven patients (8.3 %) with eight lesions. Tumor thickness over 1000 MUm (P < 0.005) and positive or inconclusive horizontal margins (P < 0.05) were significant risk factors for LNM and local recurrence, respectively. Twelve patients died because of co-existing clinical conditions. The 5-year overall and cause-specific survival rates were 80.7 % and 100 %, respectively. CONCLUSIONS: ER for SPSCC is a feasible treatment with promising results. Tumor thickness over 1000 MUm is a significant risk factor for LNM and positive or inconclusive horizontal margin is a risk factor for local recurrence. PMID- 26357671 TI - Feasibility of salvage endoscopic resection for patients with locoregional failure after definitive radiotherapy for pharyngeal cancer. AB - BACKGROUND AND STUDY AIMS: Local failure after radiation therapy for pharyngeal squamous cell carcinoma (PSCC) is problematic. The safety of endoscopic resection for lesions within the radiation therapy (RT) field has not been assessed. We evaluated salvage endoscopic resection in patients with locoregional failure after definitive radiotherapy for PSCC. PATIENTS AND METHODS: We retrospectively evaluated the clinical outcomes and long-term survival of 16 patients initially treated with more than 60 Gy of radiation for PSCC. These patients later presented with 19 superficial metachronous or recurrent PSCC lesions within the radiation field and were treated with salvage endoscopic resection. RESULTS: Local recurrence developed at the primary site in 3 patients after a complete response to RT. The other 13 had multiple metachronous squamous cell carcinomas within the original RT field. Major complications associated with salvage endoscopic resection included aspiration pneumonia in 1 patient and a requirement for temporary tracheostomy in 3 patients. During a median follow-up period of 37 months (range, 2 - 72 months), 13 patients had no recurrence, 2 patients developed local recurrence, and 1 patient developed lymph node metastases. At present, 5 of the 16 patients have died: 2 of PSCC progression, 1 of esophageal squamous cell carcinoma, and the remaining 2 of unknown causes. The 3-year survival rate was 68.6 %. CONCLUSIONS: Endoscopic resection is a potentially curative salvage treatment option for patients with superficial locoregional failure after definitive radiotherapy for PSCC. PMID- 26357672 TI - Evaluation of anesthesia management, feasibility and efficacy of peroral endoscopic myotomy (POEM) for achalasia performed in the endoscopy unit. AB - INTRODUCTION: Data on anesthesia management and outcomes associated with peroral endoscopic myotomy (POEM) performed exclusively in the endoscopy unit are limited. In this prospective study, we evaluated the safety of anesthesia management, and the feasibility and efficacy of POEM performed exclusively in the endoscopy unit. METHODS: A single-center prospective study of consecutive patients with achalasia treated with POEM in an endoscopy unit was performed. Safety of anesthesia management and POEM were determined by procedure-related adverse events. Feasibility was assessed by completion rate. Short-term efficacy was established by clinical success (Eckardt score <= 3) and by comparing Eckardt and dysphagia scores before and after POEM. RESULTS: Patients (n = 52) underwent POEM under general anesthesia with endotracheal intubation and positive pressure ventilation. Aspiration was prevented by keeping patients on a clear liquid diet before the procedure without requiring a prior esophagogastroduodenoscopy for esophageal content clearance. POEM completion rate was 96 % (50/52 patients). There was no post-POEM bleeding. Postprocedure leak was observed in one patient (3 %). Four patients (7.7 %) experienced mucosal injury, three of them were treated uneventfully endoscopically and one required laparoscopic repair. Clinical success was achieved in 88 % of patients. There was a significant decrease in the mean Eckardt score (8.1 to 1.4) and dysphagia score (2.4 to 0.4) (P < 0.0001) at the one month follow up after POEM. CONCLUSION: Anesthesia management of POEM is safe in the endoscopy unit and aspiration can be prevented without requiring prior esophagogastroduodenoscopy for esophageal content clearance. Overall, POEM performed by a gastroenterologist in the endoscopy unit was feasible and effective for the treatment of achalasia. PMID- 26357673 TI - Combined EUS and EBUS are complementary methods in lung cancer staging: Do not forget the esophagus. PMID- 26357674 TI - Endosonography for mediastinal disease: esophageal ultrasound vs. endobronchial ultrasound. AB - BACKGROUND AND STUDY AIMS: One can approach mediastinal pathology via esophageal ultrasound (EUS) and/or endobronchial ultrasound (EBUS). It has been suggested that EUS is better tolerated by patients. If so, EUS might be the procedure of choice when suspect lesions are accessible via EUS. We studied procedural characteristics of EUS with fine needle aspiration (EUS-FNA) and EBUS with transbronchial needle aspiration (EBUS-TBNA) to see how they differed. PATIENTS AND METHODS: Retrospective review of consecutive EBUS and EUS procedures performed on patients over nine months. One hundred fifty-five procedures were analyzed (61 EUS, 73 EBUS, 21 EUS + EBUS). For EUS, EBUS, and EUS + EBUS, 1.4, 2.0 and 2.5 sites (mean) were sampled, respectively. EUS required approximately one-half of the time of EBUS or the combined procedures; 13.1 vs. 24.1 and 26.9 min, respectively (P < 0.0001 for EUS vs. both EBUS and EUS + EBUS). Sedation dosing was statistically lower for EUS and not significantly different between EBUS and the combined approach. EUS also involved lower oxygen requirements and shorter time to discharge. Because fewer mean sites were sampled with EUS than with EBUS or the combined procedure, we performed analysis restricted to procedures that involved sampling of <= 2 sites to determine whether approach related differences in procedure characteristics were preserved. There were 56 such EUS procedures and 52 such EBUS procedures. EUS remained significantly faster and required less patient sedation. CONCLUSIONS: EUS involved statistically significant economies of time and sedation. This has implications with respect to safety and productivity. When applicable, EUS is the procedure of choice. PMID- 26357675 TI - Endoscopic submucosal dissection for early gastric cancer without interruption of warfarin and aspirin. AB - Many guidelines for the management of antithrombotic therapy in endoscopic procedures state that warfarin should be replaced by heparin in high risk endoscopic procedures. However, heparin bridging therapy is costly, requires a long hospital stay, and is indicated as a risk factor for bleeding after endoscopic submucosal dissection (ESD). It is not yet clear whether it is better to perform gastric ESD on continuous warfarin therapy or heparin bridging therapy. We report the case of a 65-year-old Japanese man who had been diagnosed with early gastric cancer. He had a past medical history of metallic valve replacement for mitral valve regurgitation, coronary artery disease with bare metal stent, and coronary artery bypass graft. Warfarin and low dose aspirin had been used to prevent thromboembolic events in the metallic mitral valve and coronary artery stent. We performed gastric ESD safely on continuous warfarin and low dose aspirin without any complications. PMID- 26357676 TI - Endoscopic atrophic classification before and after H. pylori eradication is closely associated with histological atrophy and intestinal metaplasia. AB - BACKGROUND AND STUDY AIMS: The relationship between endoscopic atrophy classification (EAC) and histological gastric atrophy and intestinal metaplasia (IM) was examined before and after Helicobacter pylori (H. pylori) eradication in order to evaluate the usefulness of EAC for detecting the risk of gastric cancer following eradication. PATIENTS AND METHODS: A total of 230 patients (137 males, 93 females; mean age: 58.0 +/- 11.8 y) with successful eradication were enrolled. EAC score was defined as follows: C0(none): 0, C1: 1, C2: 2, C3: 3, O1: 4, O2: 5, and O3(severe): 6. Histological atrophy and IM score (0 to 3) from the antrum and the corpus were evaluated with updated Sydney system for histological atrophy and IM. RESULTS: The mean EAC scores were 3.46 before eradication and 3.20 after eradication (P = 0.026). The mean atrophy scores before and after eradication were 1.45 and 0.92 at the antrum (P < 0.001) and 0.50 and 0.07 at the corpus (P < 0.001), respectively. The mean IM scores before and after eradication were 0.55 and 0.47 at the antrum (P = 0.154), and 0.09 and 0.05 at the corpus (P = 0.096), respectively. The histological atrophy scores showed significant improvement after eradication, while IM showed no significant change. The Mantel-Haenszel test for trend indicated there was a significant correlation between EAC and histological atrophy and IM, except antral atrophy after eradication. CONCLUSIONS: EAC exhibited a significant correlation between histological atrophy and IM, and represents a noninvasive classification method. EAC may be beneficial in evaluating the risk of gastric cancer after H. pylori eradication. PMID- 26357677 TI - Lipid is absorbed in the stomach by epithelial neoplasms (adenomas and early cancers): a novel functional endoscopy technique. AB - BACKGROUND AND STUDY AIMS: The authors have successfully demonstrated that the white opaque substance (WOS) identified in gastric epithelial neoplasms is an accumulation of minute lipid droplets on the epithelial neoplasm. It is not known whether the lipid droplets originate from externally ingested lipids (typically foods). The purpose of this study was to investigate whether the oral ingestion of foods containing emulsified fats increases the density of the WOS in epithelial neoplasms. PATIENTS AND METHODS: We examined 92 gastric epithelial neoplastic lesions in 89 patients. The patients were given emulsified fatty foods before the procedure, and magnifying endoscopy with narrow-band imaging (M-NBI) was used to image the lesions. An increase in WOS density after the ingestion of emulsified fatty foods was defined as a positive fat-loading test result. The patients were divided into the following groups: control group, no emulsified fat administered; group 1, fatty food administered 16 hours prior; group 3, fatty food administered both 16 and 4 hours prior. The proportion of positive fat loading test results was determined in all groups. RESULTS: The rates of positive fat-loading test results were as follows: control group, 9 %; group 1, 26 %; group 2, 52 %; group 3, 78 %. The increase in the rates of positive fat-loading test results in groups 2 and 3 relative to the rate in the control group was statistically significant (chi-squared test). CONCLUSIONS: This study demonstrated for the first time that the ingestion of external lipids causes lipid droplets to aggregate in situ on the gastric epithelial neoplasm. These results can be used to develop a novel functional endoscopy technique that harnesses the lipid absorption capacity of neoplasms. PMID- 26357678 TI - Diagnosis of bile duct cancer by bile cytology: usefulness of post-brushing biliary lavage fluid. AB - BACKGROUND: Pathologic evidence of biliary diseases can be obtained from cytology in addition to endoscopic retrograde cholangiopancreatography (ERCP); however, the diagnostic effectiveness is not satisfactory. STUDY AIM: This retrospective, single-center study evaluated the efficacy of various sampling methods for the cytologic diagnosis of bile duct cancer. PATIENTS AND METHODS: Biliary samples included bile that was simply aspirated, brush smear, brush-rinsed saline, and post-brushing biliary lavage fluid. A set of samples was compared for cytologic efficacy in 76 patients with surgically proven bile duct cancer and in 50 patients with benign biliary stricture. RESULTS: The cytologic sensitivity for diagnosing biliary cancer was 34 % with aspirated bile, 32 % with brush smear, 43 % with brush-rinsed saline, and 70 % with post-brushing biliary lavage fluid, in contrast to the null false-positive result in the benign cases. The sensitivity of cytology was significantly higher with post-brushing lavage fluid than with the other three sampling methods (P < 0.0001), and post-brushing lavage fluid improved the cumulative sensitivity by 24 % (P = 0.002). The sensitivity of biliary cytology was also associated with the amount of aspirated bile (P = 0.01) and with the aspiration site (P = 0.03). The rate of cancer positivity in a cytology set differed according to the tumor macroscopic type (85 % in the protruding type vs. 40 % in the flat type; P = 0.003), and according to the size of the cancer (87 % for tumors >= 50 mm vs. 66 % for tumors < 50 mm; P = 0.02). CONCLUSIONS: Post-brushing biliary lavage fluid cytology provides superior diagnostic efficacy, and its addition to ERCP procedures is recommended for obtaining cytologic evidence of bile duct cancer. PMID- 26357680 TI - Real-life conditions of use of sodium phosphate tablets for colon cleansing before colonoscopy. AB - BACKGROUND AND STUDY AIMS: The purpose of this study was to describe the real life conditions of use, efficacy, safety, and acceptability of sodium phosphate (NaP) tablets for colon cleansing in routine medical practice in France. PATIENTS AND METHODS: A total of 996 patients undergoing bowel preparation were enrolled by 108 gastroenterologists in this observational, longitudinal, prospective, multicenter study. The conditions of use of NaP tablets were assessed with a composite endpoint, which included six criteria for patient compliance with the recommended administration scheme and a criterion for the absence of contraindications to NaP use. RESULTS: Adequate use of NaP was reported for 75.1 % of the patients. The main reasons for misuse were a smaller fluid intake than expected with a dose of 4 tablets and noncompliance with age-related contraindications. The quality of cleansing was satisfactory: the Boston Bowel Preparation Scale (BBPS) total score was 7 or higher in 75.4 % of the patients. Gastroscopy associated with colonoscopy in 38.9 % of the patients revealed gastric lesions, which were considered as possibly related to the use of NaP tablets in 10.3 % of them. Vomiting occurred in 9.8 % of the patients, and 0.6 % discontinued bowel preparation after an adverse event. No electrolyte disorders or renal impairment was reported, even if not systematically sought. The acceptability of the NaP tablets was high, particularly among patients who previously had undergone other methods of bowel preparation. CONCLUSIONS: Despite being defined according to strict criteria, adequate use of NaP tablets was observed in a high percentage of patients. The quality of colon cleansing and the safety and acceptability of NaP tablets were satisfactory and consistent with data from randomized clinical studies. PMID- 26357679 TI - Efficacy and implications of a 48-h cutoff for video capsule endoscopy application in overt obscure gastrointestinal bleeding. AB - BACKGROUND AND STUDY AIMS: Early video capsule endoscopy (VCE) may provide a high diagnostic yield and improve clinical outcomes in patients with overt obscure gastrointestinal bleeding (OGIB); however, there is no practical recommendation for the ideal timing of VCE application in overt OGIB. Therefore, this study investigated the diagnostic yield and efficacy of VCE to assess overt OGIB with respect to the timing of application. PATIENTS AND METHODS: We retrospectively enrolled patients who had undergone VCE for overt OGIB between April 2004 and February 2014 at a tertiary referral academic center. We included hemodynamically stable patients who underwent VCE for overt OGIB after negative bidirectional endoscopy. We analyzed the diagnostic yield of VCE, therapeutic intervention rate, and length of hospital stay. RESULTS: A total of 94 patients underwent VCE to assess overt OGIB. The diagnostic yields in the groups that underwent VCE < 48 h and > 48 h from the last overt OGIB were 66.7 % and 40.6 %, respectively (P = 0.019). Therapeutic intervention was performed in 26.7 % and 9.4 % of patients in the < 48-h and > 48-h groups, respectively (P = 0.028). The mean lengths of hospital stay in the < 48-h and > 48-h groups were 5 days (95 % confidence interval [CI], 4.8 - 7.7) and 7 days (95 %CI, 6.9 - 10.1), respectively (P = 0.039). CONCLUSIONS: Performing VCE within 2 days from the last overt OGIB results in a higher diagnostic yield, higher therapeutic intervention rate, and shorter hospital stay. Therefore, VCE application with a 48-h cutoff could improve the outcome of patients with overt OGIB. PMID- 26357681 TI - Prospective evaluation of the proportion of sessile serrated adenoma/polyps in endoscopically diagnosed colorectal polyps with hyperplastic features. AB - BACKGROUND AND STUDY AIMS: Sessile serrated adenoma/polyps (SSA/Ps) are considered precursors of colorectal cancers with microsatellite instability. However, it is still difficult to differentiate SSA/Ps from hyperplastic polyps endoscopically; therefore, the prevalence of SSA/Ps remains uncertain in clinical practice. This study aimed to clarify the proportion of SSA/Ps in endoscopically diagnosed colorectal polyps with hyperplastic features (E-HPs). PATIENTS AND METHODS: Patients aged >= 40 years undergoing colonoscopy for standard clinical indications at our center were prospectively enrolled between June 2013 and May 2014. During colonoscopy, 0.05 % indigo carmine dye was sprayed throughout the colorectum to highlight lesions. All detected lesions were diagnosed by high definition magnifying narrow-band imaging and were resected endoscopically or surgically, apart from rectosigmoid E-HPs <= 5 mm. The number of rectosigmoid E HPs <= 5 mm was recorded, and some were resected for use as tissue samples. RESULTS: A total of 343 patients (male: 42.9 %; mean age: 61.5 years) were included. Among 3838 E-HPs (distal: 96.4 %) detected in 294 patients, 792 were resected and analyzed. All of 21 SSA/Ps identified in 17 patients were included in E-HPs, and the overall proportion of SSA/Ps in E-HPs was 2.7 %. However, this proportion increased with the size of E-HPs (<= 5 mm: 0.7 %; 6 - 9 mm: 29.0 %; >= 10 mm: 70 %) and was higher in the proximal colon than in the distal colorectum (10.9 % vs. 0.9 %). In addition, no SSA/P was found in the rectum, and no SSA/P had cytological dysplasia. CONCLUSIONS: The overall proportion of SSA/Ps in E-HPs was 2.7 %, although this proportion was higher in the proximal colon and increased with the size of E-HPs. SSA/Ps were common in routine colonoscopy, with a prevalence of at least 5.0 %. STUDY REGISTRATION: UMIN000010832. PMID- 26357682 TI - Preoperative classification of submucosal fibrosis in colorectal laterally spreading tumors by endoscopic ultrasonography. AB - BACKGROUND AND STUDY AIMS: Although endoscopic submucosal dissection (ESD) is an established therapy for colon neoplasms including laterally spreading tumors (LSTs), its application to advanced fibrotic lesions is very difficult owing to the thin walls of the large intestine. We examined the ability of preoperative endoscopic ultrasonography (EUS) to predict lesion fibrosis in patients undergoing colorectal ESD. PATIENTS AND METHODS: From 2009 to 2013, 58 LSTs were evaluated retrospectively with EUS and treated using colorectal ESD. The degree of submucosal fibrosis was determined during ESD and classified as F0 (no fibrosis), F1 (mild fibrosis), or F2 (severe fibrosis). RESULTS: The sensitivity and specificity of fibrosis prediction by preoperative EUS of all cases were 77.8 % and 57.1 %, respectively. However, there was a high accuracy (97.2 %, 35/36) for only the 36 LSTs with clear and visible images. In one case, EUS diagnosed no fibrosis but significant fibrosis was found during ESD, the result of colon cancer invasion into the submucosa. CONCLUSIONS: Preoperative EUS before colorectal ESD successfully predicted the degree of fibrosis in a number of cases. PMID- 26357683 TI - Opioid use among same-day surgery patients: Prevalence, management and outcomes. AB - OBJECTIVES: To determine whether the prevalence of opioid use among patients requiring elective same-day admission (SDA) surgery is greater than the 2.5% prevalence found in the general population. Secondary objectives were to assess compliance with expert recommendations on acute pain management in opioid tolerant patients and to examine clinical outcomes. METHODS: A retrospective review of 812 systematically sampled adult SDA surgical cases between April 1, 2008 and March 31, 2009 was conducted. RESULTS: Among 798 eligible patients, 148 (18.5% [95% CI 15.9% to 21.2%]) were prescribed opioids, with 4.4% prescribed long-acting opioids (95% CI 3.0% to 5.8%). Use of opioids was most prevalent among orthopedic and neurosurgery patients. Among the 35 patients on long-acting opioids who had a high likelihood of being tolerant, anesthesiologists correctly identified 33, but only 13 (37%) took their usual opioid preoperatively while 22 (63%) had opioids continued postoperatively. Acetaminophen, nonsteroidal anti inflammatory drugs and pregabalin were ordered preoperatively in 18 (51%), 15 (43%) and 18 (51%) cases, respectively, while ketamine was used in 15 (43%) patients intraoperatively. Acetaminophen, nonsteroidal anti-inflammatory drugs and pregabalin were ordered postoperatively in 31 (89%), 15 (43%) and 17 (49%) of the cases, respectively. No differences in length of stay, readmissions and emergency room visits were found between opioid-tolerant and opioid-naive patients. CONCLUSION: Opioid use is more common in SDA surgical patients than in the general population and is most prevalent within orthopedic and neurosurgery patients. Uptake of expert opinion on the management of acute pain in the opioid tolerant patient population is lacking. PMID- 26357685 TI - Teddy and I get a check up: A pilot educational intervention teaching children coping strategies for managing procedure-related pain and fear. PMID- 26357684 TI - Analysis of radiofrequency lesions in egg whites in vitro produced by application of the Tew electrode for different temperatures and times. AB - BACKGROUND: Understanding the size and shape of radiofrequency lesions is important to reduce side effects when applied to patients. OBJECTIVES: To investigate the radiofrequency lesions produced by the application of the Tew electrode for different temperatures and times. METHODS: The white from a fresh hen's egg was placed in a rectangular glass container and warmed to 37 degrees C. After immersion of the Tew electrode in the egg white, radiofrequency lesions were produced at 65 degrees C, 70 degrees C, 75 degrees C, 80 degrees C, 85 degrees C and 90 degrees C. For each temperature, photographs were taken at 10 s, 20 s, 30 s, 40 s, 50 s, 60 s, 70 s, 80 s, 90 s, 100 s, 110 s and 120 s. The size of the lesion was measured at each temperature and time. A mixed model was used to analyze the data. RESULTS: The size of the lesion increased with increasing temperature and time. There were statistically significant differences in the size of the internal radius between the 65 degrees C and 70 degrees C groups and the 70 degrees C and 75 degrees C groups, as well as in the 70 degrees C and 75 degrees C groups in the size of the external radius and the 60 degrees C to 80 degrees C groups in the size of the distal radius. The maximum lesion size was produced at 90 degrees C and 120 s, and was 1.06+/-0.16 mm in internal radius, 0.37+/-0.15 mm in external radius, 0.39+/-0.04 mm in distal radius. CONCLUSION: The Tew electrode produces lesions following the contour of the tip, and the internal radius is larger than the external and distal radius. The best combination of temperature and time for lesioning using the Tew electrode is 80 degrees C, for 60 s to 90 s. PMID- 26357687 TI - Pain catastrophizing correlates with early mild traumatic brain injury outcome. PMID- 26357689 TI - Physicians' attitudes toward clinical pain management and education: Survey from a Middle Eastern country. PMID- 26357688 TI - The influence of medical evidence moderators on pain rating agreement between inpatients and nurses. PMID- 26357686 TI - Spinal antinociceptive action of amiloride and its interaction with tizanidine in the rat formalin test. AB - BACKGROUND: Amiloride has been reported to produce a wide variety of actions, thereby affecting several ionic channels and a multitude of receptors and enzymes. Intrathecal alpha2-adrenergic receptor agonists produce pronounced analgesia, and amiloride modulates alpha2-adrenergic receptor agonist binding and function, acting via the allosteric site on the alpha2A-adrenergic receptor. OBJECTIVES: To investigate the antinociceptive interaction of intrathecal amiloride and the alpha2-adrenoceptor agonist tizanidine using a rat formalin test. METHODS: Sprague-Dawley rats were chronically implanted with lumbar intrathecal catheters and were tested for paw flinching using formalin injection. Biphasic painful behaviour was recorded. Amiloride, tizanidine or an amiloride tizanidine mixture was administered 10 min before formalin injection. To characterize any interactions, isobolographic analysis was performed. The effects of a pretreatment using intrathecally administered yohimbine was also tested. RESULTS: Intrathecally administered amiloride (12.5 MUg to 100 MUg) and tizanidine (0.5 MUg to 5 MUg), given separately, produced a significant dose related suppression of the biphasic responses in the formalin test. Isobolographic analysis revealed that the combination of intrathecal amiloride and tizanidine synergistically reduced phase I and II activities. Intrathecally administered yohimbine antagonized or attenuated the antinociceptive effect of amiloride, tizanidine and the amiloride-tizanidine mixture. Intrathecally administered amiloride synergistically interacts with tizanidine to reduce the nociceptive response in the formalin test, most likely by activating alpha2 adrenoceptors in the spinal cord. CONCLUSIONS: Although intrathecal tizanidine produced pronounced analgesia, antinociceptive doses of intrathecal tizanidine also produced several side effects, including bradycardia and sedation. Amiloride produced antinociceptive action against the thermal nociceptive test without side effects in rats. PMID- 26357690 TI - A Standardized Approach for the Early Restorative Phase After Esthetic Crown Lengthening Surgery. AB - The aim of the present case series article was to provide a standardized approach for the early restorative phase after a crown-lengthening surgical procedure. Different advantages can be ascribed to this approach: the clinician can prepare a definitive prosthetic finishing line in the supragingival location; the early postsurgical temporization allows the conditioning of soft tissues, especially the interdental papillae, during their maximum growing phase; and the clinician can choose the time for the definitive prosthetic rehabilitation in a patient specific manner according to the individual potential and duration of the soft tissue rebound. In this study, this standardized approach was applied to the treatment of two esthetic cases requiring crown-lengthening procedures. PMID- 26357691 TI - Vertical Ridge Augmentation and Soft Tissue Reconstruction of the Anterior Atrophic Maxillae: A Case Series. AB - Severe vertical ridge deficiency in the anterior maxilla represents one of the most challenging clinical scenarios in the bone regeneration arena. As such, a combination of vertical bone augmentation using various biomaterials and soft tissue manipulation is needed to obtain successful outcomes. The present case series describes a novel approach to overcome vertical deficiencies in the anterior atrophied maxillae by using a mixture of autologous and anorganic bovine bone. Soft tissue manipulation including, but not limited to, free soft tissue graft was used to overcome the drawbacks of vertical bone augmentation (eg, loss of vestibular depth and keratinized mucosa). By combining soft and hard tissue grafts, optimum esthetic and long-term implant prosthesis stability can be achieved and sustained. PMID- 26357692 TI - Peri-implantitis Treatment with a Regenerative Approach: Clinical Outcomes on Reentry. AB - This case series presents clinical outcomes on reentry using regenerative submerged and nonsubmerged approaches in peri-implant defects; pre- and posttreatment assessments of nine implants in six patients are presented. A mean bone fill value of 91.3% with a 4.88-mm mean bone gain was obtained. Neither approach led to additional bone loss or required additional bone augmentation procedures. Strict methods of implant surface decontamination and detoxification were used on all patients, regardless of implant surface characteristics. The regenerative procedure was effective in the treatment of moderate to advanced peri-implantitis lesions without compromising the previous fixed implant supported prostheses. These preliminary results are reasonably encouraging in that all cases showed bone gains. Nevertheless, caution must be exercised when determining reosseointegration, because it is not possible to ascertain it in clinical practice. PMID- 26357693 TI - Root Coverage of Multiple Miller Class I and II Recession Defects Using Acellular Dermal Matrix and Tunneling Technique in Maxilla and Mandible: A 1-Year Report. AB - The objective of the present report was to study the influence of the location (maxilla versus mandible) and class (Miller classification) of gingival recessions on the total root coverage achievement using the tunnel procedure with acellular dermal matrix in adjacent single-root teeth. Twenty-four patients with 93 recessions were treated and evaluated 1 year postsurgery. Results showed 100% of root covered in 67.9% of the maxillary recessions and 52.5% in the mandible (P = .676). In cases of partial root coverage, the initial recession diminished from 4.41 mm (SD: 1.12) to 0.82 mm (SD: 0.24) in the maxilla and from 3.78 mm (SD: 1.08) to 0.78 mm (SD: 0.30) in the mandible. Root coverage of 100% was observed in 74.07% of Miller Class I recessions in comparison with 43.59% of Class II recessions (P = .003). PMID- 26357694 TI - Reentry After Combined Surgical Resective and Regenerative Therapy of Advanced Peri-implantitis: A Retrospective Analysis of Five Cases. AB - This retrospective analysis of five reentry cases reports on the clinical defect healing after combined surgical resective/regenerative therapy of advanced peri implantitis. A second surgery was necessary because of a clinical need for additional treatment procedures at the respective implant sites after healing periods of 8 months to 6.5 years. All patients underwent the same standardized procedure including access flap surgery, implantoplasty at bucally and supracrestally (> 1 mm) exposed implant parts, surface decontamination, and augmentation of the intrabony (Class I) components using a natural bone mineral and a native collagen membrane. Clinical defect resolution (DR) of the Class I component was evaluated. In two patients, clinical and radiographic signs suggested a reinfection (ie, case 3-mesial aspect; case 5-mesial and distal aspects). Mean DR values +/- standard deviation were 59.4% +/- 47.59% (95% confidence interval [CI], 0.31%-118.49%). When infected aspects were excluded, resulting values were 85.76% +/- 4.86% (95% CI, 78.02%-93.50%). The presented surgical procedure was associated with a clinically important DR in advanced peri implantitis defects. PMID- 26357695 TI - Critical Evaluation of Complete Root Coverage as a Successful Endpoint of Treatment for Gingival Recessions. AB - Two differing evaluation criteria for complete root coverage (CRC) were used to compare incidence of CRC after root coverage procedures. Clinical records of 363 patients (386 single recessions) treated between 1984 and 2012 were screened. CRC was assessed 1 year after surgery using two separate evaluation criteria: CRC1, in which the gingival margin was at or above the cementoenamel junction (CEJ), measured using a periodontal probe directly on patients by a single examiner; and CRC2, in which the gingival margin was above the CEJ, rendering it completely invisible based on a visual assessment of high-magnification digitalized images by two calibrated examiners. Descriptive and inferential statistics were performed. The k statistic was also calculated to test the agreement between the two examiners. Four treatment groups were identified: free gingival graft (FGG; n = 116), coronally advanced flap (CAF; n = 107), CAF + connective tissue graft (CTG; n = 131) and guided tissue regeneration (GTR; n = 32). The overall difference between the proportion of CRC1 and CRC2 was statistically significant (P < .0001), as were the intragroup differences for FGG (P = .0002), CAF (P = .0009), and CTG (P = .0002). Treatment of gingival recessions should only be deemed completely successful when root coverage is associated with a gingival margin and a crevice probing depth that is coronal to the CEJ. When root coverage is regarded as complete with gingival margin located at the level of CEJ, it does not represent complete treatment success. PMID- 26357696 TI - Influence of Periodontal Biotype on Root Surface Exposure During Orthodontic Treatment: A Preliminary Study. AB - The aim of this study was to investigate the role of periodontal biotype in the development of gingival recession in patients who have undergone orthodontic treatment. A total of 60 mandibular incisors were analyzed. The qualitative assessment of periodontal biotype was performed with the use of a new biotype probe. A strong correlation was found between thin biotype and proinclination in terms of recession depth and keratinized tissue width. Patients with thin periodontal biotype are more prone to gingival margin instability, irrespective of the type of orthodontic movements. Thin periodontal biotype and proinclination orthodontic movement were related to loss of keratinized tissue width. PMID- 26357697 TI - Evaluation of Dental Implants Placed in Preserved and Nonpreserved Postextraction Ridges: A 12-Month Postloading Study. AB - Forty-eight single dental implants were inserted 4 months after tooth extraction following ridge preservation (RP; n = 24) or spontaneous healing (EXT; n = 24). During surgery, 1 (7%) of 24 implants in the RP group and 14 (58%) of 24 in the EXT group required additional bone grafting, and the implant stability quotient value was similar in the two groups. The survival rate of the implants in both groups was 100% at the 1-year follow-up. The success rate was 95.83% in the RP group and 91.66% in the EXT group. No statistically significant differences in the marginal bone level were detected between the two groups. Similar outcomes of implants inserted in preserved or spontaneously healed ridges can be anticipated, but the use of an RP procedure reduces the need for further bone augmentation. PMID- 26357698 TI - Eleven-Year Retrospective Survival Study of 275 Veneered Lithium Disilicate Single Crowns. AB - The aim of the present clinical retrospective study was to evaluate the long-term survival and clinical performance of veneered lithium disilicate single restorations in anterior and posterior areas after up to 11 years. Following a rigid protocol, 275 lithium disilicate single crowns (35 IPS Empress II and 240 e.max Press) were cemented over 11 years, in 106 patients, using an adhesive technique; of these 106 were anterior (38.5%) and 169 posterior (61.5%) teeth. Teeth receiving endodontic therapy and composite reconstruction (50%) and teeth with preexisting metalceramic crowns, called prosthetic retreatments (PR; 65%), were included as well. Of the 106 patients enrolled in the study, 25 (23.5%) were diagnosed with bruxism habits, and 7 of these patients (6.6% of all patients) received full-mouth single lithium disilicate restorations (FMR). The exclusion criteria for this retrospective clinical study were: monolithic lithium disilicate crowns, teeth with cast post and cores, implant-supported all-ceramic crowns, active periodontitis, and/or poor oral hygiene. Clinical reevaluation was performed by the clinicians who prepared and luted them during maintenance appointments between January 2012 and October 2013. Number of restoration failures and characteristics of failures were recorded. Marginal adaptation and marginal discoloration were evaluated based on the Cvar-Ryge criteria. The overall cumulative survival rate was 98.2%. The failures recorded were the result of either mechanical failure or debonding. Five crowns failed mechanically-three because of chipping and two because of core fracture-and were replaced. None of the failed crowns was associated with the bruxers with FMR. A total of 15 crowns debonded (5.5% of all crowns); however, 11 belonged to the same patient who had endodontically treated and reconstructed abutments. In this retrospective clinical evaluation of up to 132 months, veneered lithium disilicate single crowns had a low failure rate. PMID- 26357699 TI - Implant Site Development by Horizontal Tooth Movement to an Esthetic Area: A Case Report. AB - This case report describes the treatment of a woman who lost a central incisor. The socket developed severe tissue defects. She rejected hard and soft tissue management and the use of biomaterials. The lateral incisor was moved mesially with orthodontic treatment. The tissue defects were filled with the alveolar bone of the moved tooth and adequate bone volume was generated behind it. An implant was placed in the space that was generated without any tissue augmentation. The moved tooth had sound periodontal tissue and was restored without preparation. The horizontal tooth movement enabled an esthetic outcome with minimal intervention. PMID- 26357700 TI - Palatal Augmentation Technique: A Predictable Method to Increase the Palatal Connective Tissue at Donor Sites- A Consecutive Case Series. AB - The palatal masticatory mucosa between the canine and first molar is the main source of connective tissue graft (CTG) for use in periodontal plastic surgery. The purpose of this study was to evaluate the palatal augmentation technique (PAT) to increase the palatal connective tissue donor area using a collagen sponge inserted between the palatal flap and bone. The 26 patients enrolled in this study were referred for root coverage and ridge augmentation procedures. All patients lacked adequate donor palatal tissue thickness. The PAT uses a full thickness flap and insertion of a sterile lyophilized bovine collagen sponge between the flap and bone. The palatal thickness was clinically assessed before and after collagen sponge insertion. A manual probe was inserted in the mucosal surface perpendicular to the long axis of each tooth approximately 6 mm from the gingival margin. Probing depth (PD) and recession (REC) were also recorded. Treatment with PAT resulted in a statistically significant increase in the palatal thickness. The overall mean increase was from 2.03 mm before surgery to 3.57 mm after surgery, with no major alterations in PD and REC. Healing proceeded uneventfully and occurred by primary intention. PAT appeared to be a predictable procedure to create connective tissue donor graft in deficient areas and had uneventful postoperative healing. PMID- 26357701 TI - Immediate Implant Placement and Loading of Single Implants in the Esthetic Zone: Clinical Outcome and Esthetic Evaluation in a Japanese Population. AB - This study evaluated the clinical outcomes of immediately loaded maxillary anterior single implants placed in fresh extraction sockets. A patient cohort that was treated 1.5 years earlier was recalled, and 18 patients (6 men, 12 women) with 21 implants were included. Clinical photographs and periapical radiographs were taken at follow-up and baseline to determine the bone loss and change in esthetics. No marginal bone loss was detected at follow-up (mean bone level +/- standard deviation = 0.32 +/- 0.82 mm). Immediate implant placement and loading resulted in predictable clinical and esthetic outcomes, with soft and hard tissue levels remaining stable over time. PMID- 26357702 TI - Immediately Loaded Intraorally Welded Complete-Arch Maxillary Provisional Prosthesis. AB - Guided implant surgery is not completely accurate when using computer-designed stereolithographic surgical guides. Complications are frequently reported when combining computer-guided flapless surgery with an immediately loaded prefabricated prosthesis. Achieving passive fit of a prefabricated prosthesis on the inserted implants the same day of the surgery can be difficult. The aim of this report is to show a new treatment approach to immediately loaded implants inserted with computer-guided surgery using an intraoral welded full-arch provisional prosthesis. PMID- 26357703 TI - Microvessel Density Evaluation of the Effect of Enamel Matrix Derivative on Soft Tissue After Implant Placement: A Preliminary Study. AB - Enamel matrix derivative (EMD) is commonly used in periodontal therapy and has been used successfully for periodontal regeneration. In addition, this material has a possible angiogenic effect that has been associated with enhanced wound healing. The aim of this study was to evaluate the effect of EMD on microvessel density (angiogenesis) on the soft tissues surrounding newly placed implants after 14 days. Five patients were selected, each requiring at least one implant on each side of the maxilla, in a split-mouth experimental design. The implants were placed in a two-stage procedure. Each side was then randomized as test or control. On the test side, 0.1 mL of EMD was topically applied to the soft tissues surrounding the implants, while the control side did not receive any treatment. Second-stage surgery was performed after 14 days. A 6-mm punch biopsy was performed for each implant, with the samples subsequently prepared for histology and immunohistochemistry. Quantitative vascularization analysis was performed, which involved counting three areas or "hotspots" containing vessels strongly positive for CD34 and CD105, a pan-endothelial and new vessel marker, respectively. There was no significant difference between test and control groups when evaluating the formation of new blood vessels. The total number of blood vessels, however, was significantly higher in the group treated with EMD (test group). Within the limits of the present study, it can be concluded that topical application of EMD on the soft tissues surrounding newly placed implants resulted in an increased number of blood vessels at 14 days, suggesting that EMD may play a beneficial role in this aspect of wound healing. PMID- 26357704 TI - Effects of Dentin Surface Treatments on Hypersensitivity to Bond Strength of Restorations: An In Vitro Study. AB - This study evaluated the effects of desensitizing treatments on the shear bond strength (SBS) of adhesive resin cement (Rely X U100) applied to dentin. Human molars (n = 120) with exposed dentin were divided into 12 groups. In the experimental groups, dentin surfaces were treated with (1) an erbium:yttrium- aluminium-garnet (Er:YAG) laser, (2) a neodymium:yttrium-aluminium-garnet (Nd:YAG) laser, (3) glutaraldehyde (Gluma)-, (4) fluoride (Aqua Prep-F)-, and (5) oxalate (BisBlock)-containing desensitizing agents, (6) Gluma preceding the Er:YAG laser, (7) Aqua Prep-F preceding the Er:YAG laser, (8) BisBlock preceding the Er:YAG laser, (9) Gluma preceding the Nd:YAG laser, (10) Aqua Prep-F preceding the Nd:YAG laser, (11) and BisBlock preceding the Nd:YAG laser, in groups EL, NL, G, F, O, EL-G, EL-F, EL-O, NL-G , NL-F, and NL-O, respectively. Then, lithium disilicate ceramics were cemented to the treated surfaces. Subsequently, an SBS test was performed and the data were statistically analyzed (alpha = .001). The results suggested that the combined treatment of Gluma preceding Er:YAG laser increased the bond strength of ceramic to the dentin surface using a self-adhesive resin cement. PMID- 26357705 TI - Surgical Site Assessment for Soft Tissue Management in Ridge Augmentation Procedures. AB - The success of bone augmentation is usually dependent on primary wound closure. This review provides a literature-based system to assess the predictability of achieving primary wound closure. Seven pertinent factors that determine the risk for wound exposure were identified: (1) the width of keratinized mucosa, (2) flap thickness, (3) flap tension, (4) vestibular depth, (5) type and (6) size of the bony defect, and (7) materials used. Clinical cases are used to demonstrate evaluation of these factors. This evaluation system may aid clinicians in differentiating cases with various risks of wound exposure and making decisions on flap modifications and the most appropriate surgical designs. PMID- 26357706 TI - Obtaining complementary polypeptide sequence information from a single precursor ion packet via sequential ion mobility-resolved electron transfer and vibrational activation. AB - Tandem mass spectrometry (MS/MS) is now well-known as a powerful tool for characterizing the primary structures of peptides and proteins; however, in many cases the use of but a single dissociation method provides only a partial view of the amino acid sequences and post-translational modification patterns of polypeptides. While the application of multiple fragmentation methods can be more informative, this introduces the burden of acquiring multiple MS/MS spectra per analyte, thus reducing the effective duty cycle of such methods. In this work, initial proof-of-concept is provided for a method designed to overcome these barriers. This method relies on the complementary fragmentation information that can be provided by performing collision-induced dissociation (CID) and electron transfer dissociation (ETD) in concert, while also taking advantage of an ion mobility (IM) dimension to temporally resolve the occurrence of CID and ETD when applied to a single accumulated packet of precursor ions. In this way, the significant proportion of the precursor ion population that remains unreacted in ETD experiments is subjected to CID rather than being fruitlessly discarded. In addition, the two distinct fragmentation spectra can be extracted from their corresponding IM domains to render readily interpretable individual fragmentation spectra. This scheme was demonstrated for several polypeptides ranging from 1.3 to 8.6 kDa in molecular weight. In each case, IM-resolved CID and ETD events resulted in b/y and c/z ions, respectively, which each covered both unique and overlapping sequence information. These findings demonstrate that the combination of CID and ETD can be achieved with greater utilization of the available ion population and little or no loss of duty cycle. PMID- 26357707 TI - Curcumisome nanovesicles generated by self-assembly of curcumin amphiphiles toward cancer theranostics. AB - Curcumin (CCM) is an important molecule for achieving cancer theranostics because CCM is a naturally-occurring biocompatible material that exhibits both anticancer activity and strong fluorescence property that can be used for bio-imaging. However, CCM has never been utilized in clinical trials due to its extremely low water solubility, its rapid hydrolysis in aqueous conditions at neutral pH, and its low cellular uptake into cancer cells. Taking advantage of the strong hydrophobicity, pi-conjugated frameworks, and ketone and enol groups that generate hydrogen bonds in CCM, we herein fabricated novel CCM-based biodegradable nanovesicles, which we termed as "curcumisome", through the self assembly of amphiphilic CCM-poly(ethylene glycol) conjugates in aqueous media to develop multifunctional nanobiomaterials for use in cancer theranostics. A high CCM loading content in the curcumisomes was achieved, and the curcumisomes showed high water dispersibility with improved hydrolysis resistance. Importantly, the curcumisomes were effectively internalized into cancer cells and exhibited strong fluorescence for a long period, which is favorable for cancer cell imaging, although only a small amount of the curcumisomes penetrated into normal cells and showed very weak fluorescence. Moreover, curcumisomes effectively induced apoptosis of cancer cells. Thus, curcumisomes may act as multifunctional nanobiomaterials for the development of CCM-based cancer theranostics. PMID- 26357708 TI - Retracted: Performance differences between male and female marines on standardized physical fitness tests and combat proxy tasks: identifying the gap. PMID- 26357710 TI - Findings of research misconduct. PMID- 26357709 TI - Findings of research misconduct. PMID- 26357711 TI - Big data, big stories and the stones in our shoes--how neglecting the foundation can trip us up. PMID- 26357712 TI - Diagnostic Use of Endoscopic Retrograde Cholangiopancreatectography for Pancreatic Duct Injury in Trauma Patients. AB - BACKGROUND: Trauma patients diagnosed with pancreatic duct injury (PDI) have a high complication rate and prolonged hospital stay. The role of endoscopic retrograde cholangiopancreatography (ERCP) in the diagnosis of PDI remains unclear. During the last decade, our trauma unit incorporated ERCP into the management protocol for suspected PDI cases. OBJECTIVES: To determine whether ERCP is a sensitive tool to detect PDI. METHODS: This retrospective trauma patient series study assessed the diagnostic yield of ERCP in trauma cases with suspected PDI on computed tomography (CT) or intraoperatively. Between 1 January 2004 and 31 December 2011, 13 patients admitted to our medical center underwent ERCP for suspected PDI. Patient demographics, mechanism of injury, Injury Severity Score (ISS), time from injury to ERCP, and ERCP-related complications were documented and assessed. RESULTS: Of the 13 patients included in the analysis, 8 stable patients with suspected PDI on CT had no leak from the main pancreatic duct on ERCP. Two of them underwent surgery for suspected pancreatic transection. ERCP confirmed a main pancreatic duct leak in three patients. Two patients underwent ERCP for suspected PDI after "damage control" surgery. No leak from the pancreatic ducts was diagnosed. No pancreas-related complications or ERCP-related complications were observed. CONCLUSIONS: ERCP is a sensitive and relatively safe tool for the diagnosis of PDI, and its use might prevent unnecessary surgical interventions in selected trauma cases. PMID- 26357713 TI - Interferon Gamma Release Assay-Guided Latent Tuberculosis Prophylaxis in Israel. AB - BACKGROUND: Determining the accuracy of interferon gamma-release assays (IGRAs) is difficult due to the lack of a gold standard test for diagnosing latent tuberculosis (LTB). OBJECTIVES: To analyze the guidelines used for interpreting IGRAs in determining prophylactic treatment management for latent tuberculosis (LTB) in Israel. METHODS: We analyzed the retrospective data of 367 subjects who were referred to our laboratory during the period 2007-2011 for QuantiFERON Test Gold In Tube (QFT-GIT) tests because of suspected LTB. Demographics and clinical data were retrieved from a questionnaire at enrollment, and 166/367 (45%) were further interviewed by phone in order to complete follow-up information on prophylactic TB treatment. RESULTS: The majority of subjects (116/166, 69.9%, P (P < 0.0001) were spared prophylactic treatment subsequent to QFT-GIT testing. Subjects with negative QFT-GIT and positive tuberculin skin test (TST) results who were BCG-vaccinated had the lowest treatment rates (6/68, 8.8%, P < 0.0001). Most BCG-vaccinated subjects with positive TST and negative QFT-GIT test results received treatment with anti-tumor necrosis factor-alpha (TNFalpha) (17/19, 89.5%, P = 0.004). We found more negative QFT-GIT test results in subjects who were receiving anti-TNFalpha or steroid and other immunosuppressive treatment prior to testing (11/11, 100%, P = 0.029; 22/26, 84.6%, P = 0.06; 15/17, 88%, P = 0.06, respectively). CONCLUSIONS: Deciding on LTB prophylactic treatment in Israel is highly influenced by QFT-GIT test results. QFT-GIT findings contribute to clinical decisions, but their interpretation must also consider the patient's medical history and clinical characteristics. PMID- 26357714 TI - Use of Automated Breast Volumetric Sonography as a Second-Look Tool for Findings in Breast Magnetic Resonance Imaging. AB - Breast magnetic resonance imaging (MRI) has an important role in the detection and diagnosis of breast cancer. Suspicious findings on MRI are further evaluated with ultrasound. This case series illustrates the use of automated breast volumetric ultrasound (ABVS) as a tool for second-look ultrasound (SLUS) following MRI. Seven women underwent breast MRI with findings necessitating SLUS. ABVS was used for second look and all MRI lesions were detected. Four cancers, one fibroadenoma and two benign lesions, were diagnosed. This case series shows that ABVS can be used as a tool for SLUS following MRI and in some cases is superior to hand-held ultrasound. PMID- 26357715 TI - Toxicity of Treatment for Anal Carcinoma: 2D versus 3D Planning. AB - BACKGROUND: Anal cancer is a relatively uncommon disease, accounting for only 4% of cancers of the lower gastrointestinal tract. OBJECTIVES: To summarize a single center experience in the treatment of anal carcinoma using various radiation techniques. METHODS: We conducted a retrospective chart review of consecutive patients who were treated for anal cancer between the years 2002 and 2011. The data extracted included demographics, type of radiation technique, treatment associated acute toxicity, and patterns of failure and survival. For statistical analysis purposes, the patients were divided into two groups according to radiotherapy technique: 2D (group A) and 3D (group B). RESULTS: A total of 42 patients--25 (59.5%) females and 17 males (40.5%)--underwent definitive chemo radiation treatment (CRT) for anal cancer. Group A comprised 26 patients and group B 14 patients. Toxicity did not differ significantly between the groups; only in grade 1-2 skin toxicity which was more common in group B. There were significant differences in the unplanned interruptions in treatment, in both the number of patients who needed a treatment break and the number of days needed (more in group A). There were no differences in treatment response and patterns of failure between these two techniques, or in overall survival between the two groups. CONCLUSIONS: Our study results are consistent with reported large randomized trials, indicating that current treatments for anal carcinomas are associated with high grade acute toxicity that may result in significant treatment interruptions. The 2D technique was associated with significantly more treatment interruptions but did not differ from 3D with regard to treatment efficacy. PMID- 26357716 TI - Mycetoma of the Foot Caused by Madurella Mycetomatis in Immigrants from Sudan. AB - BACKGROUND: Mycetoma is a chronic and destructive infection caused by either fungus or bacteria. Mycetoma has a characteristic clinical presentation of a triad of tumor-like swelling, draining sinuses, and macroscopic grains. Mycetoma infection is extremely rare in Israel; however, in view of the recent immigration from mycetoma-hyperendemic regions of Africa to Israel, physicians in Israel may encounter this infection. OBJECTIVES: To present two cases of mycetoma caused by Madurella mycatomatis in immigrants from endemic regions in Sudan treated at our hospital, and review the current literature. CONCLUSIONS: Health care professionals in Israel should suspect mycetoma in patients from endemic countries who present with tumor-like swelling especially in the lower extremity. Health care workers should be able to recognize mycetoma and provide the optimal treatment before the lesion progresses to an advanced and disabling disease. PMID- 26357717 TI - Implementation of a Policy Change: Replacement of Nebulizers by Spacers for the Treatment of Asthma in Children. AB - BACKGROUND: Treatment using inhaled bronchodilators for asthma with a metered dose inhaler attached to a spacer device (MDI+S) was shown to be as efficient as nebulizers. Nevertheless, nebulizers remain the treatment of choice in most hospitals. OBJECTIVES: To implement a policy change to improve asthma treatment in pediatric wards and the pediatric emergency department. METHODS: The study was performed in the emergency department and pediatric wards of a university medical center. The study group comprised all children admitted with a diagnosis of asthma necessitating treatment. The medical and nursing staff of both the pediatric emergency department and the pediatric wards was trained how to use metered dose inhalers attached to spacers on a regular basis in asthmatic pediatric patients. At a preset date nebulizers were replaced by spacers and their use was monitored by the supervising physician. Salbutamol was administered by a metered dose inhaler (100 MUg/puff) attached to a spacer device. The number of puffs was determined by severity of disease according to GINA recommendations. After 2 years the outcome and cost analysis were examined. RESULTS: During 3 years since the initial policy change 92.5%, patients were treated with spacers throughout their hospital stay (emergency department and pediatric ward). Costs were reduced by an estimated 63%. CONCLUSIONS: In view of its many advantages, replacing nebulizers by MDI+S for the treatment of acute asthma.is, feasible, if performed in collaboration with the staff, hospital authority and patients. PMID- 26357718 TI - Hyperglycemia in Diabetic Patients in General Medicine Wards: No independent correlation with In- and Out-Of-Hospital Mortality. AB - BACKGROUND: Admission glucose levels correlate with clinical outcome in patients with type 2 diabetes mellitus (T2DM) hospitalized in general medicine wards. OBJECTIVE: To investigate whether in-hospital hyperglycemia alone, and after adjustment for age, gender and lipidemia, correlates with in- and out-of-hospital mortality. METHODS: Capillary glucose, serum lipids and diagnoses at discharge among patients with T2DM hospitalized in the general medical wards of our hospital were documented. Correlation with in- and out-of-hospital mortality was determined through uni- and multivariate analyses. RESULTS: Of the 4607 patients included in the study 22% died while hospitalized. From a median of five capillary glucose tests obtained per patient, average capillary glucose level was significantly lower in those who survived than in those who died (174 +/- 64 vs. 180 +/- 65 mg/dl, P = 0.005). Overall, blood cholesterol was higher in those who survived than in those who died (P < 0.001). Multivariate analysis, however, including age, gender, lipidemia and glycemia, showed that only age and male gender correlated with mortality. CONCLUSIONS: Hyperglycemia was associated with increased in- and out-of-hospital mortality on univariate analysis. However, it was not an independent risk factor when corrected for age, gender and hyperlipidemia. PMID- 26357719 TI - Lobectomy for Non-Small Cell Lung Cancer after Coronary Artery Bypass Grafting Surgery. AB - BACKGROUND: The efficacy of video-assisted thoracoscopic surgery lobectomy in patients with previous coronary artery bypass grafting (CABG) surgery is controversial. OBJECTIVES: To investigate whether skeletonized left internal mammary artery (LIMA) mobilization contributes to the development of severe adhesions, which will affect what type of lung surgery (open or closed procedure) will be required in the future. METHODS: Eight patients (mean age 73.9 years) with previous CABG surgery using a LIMA to left anterior descending (LAD) graft underwent left-sided lobectomy for operable non-small cell lung carcinoma. RESULTS: The lobectomy by thoracotomy rate was 62.5% (5 patients), generally in patients with tumors in the left upper lobe or in patients post-neoadjuvant chemotherapy, while the video-assisted thoracic surgery lobectomy rate was 37.5% (3 patients). Mean hospital stay was 8.3 days. There was no mortality or major morbidity, apart from six minor complications in four patients (50%) (air leak, atrial fibrillation, atelectasis, pneumonia). CONCLUSIONS: Patients with operable non-small cell lung carcinoma following CABG surgery who need left upper lobe resection do not benefit from the video-assisted thoracoscopic surgery technique due to significant adhesions between the LIMA to LAD graft and the lung. The method of preserving a small portion of the lung on the LIMA to LAD graft may help during left upper lobe resections. Adhesions in the left pleural space after LIMA mobilization appear to minimally affect left lower lobe video-assisted thoracoscopic surgery. PMID- 26357720 TI - Influence of Demography and Personality on Patient Choice of Treatment in Symptomatic Benign Prostate Hyperplasia. AB - Background: Benign prostate hyperplasia (BPH) is a common age-dependent urological condition that can adversely affect quality of life if the patient's treatment choice is inap- propriate. OBJECTIVES: To examine whether patients' demography and personality affect their decision regarding the type of treatment: namely, conservative or surgical. METHODS: A total of 105 BPH patients treated during the period 2005-2008 were retrospectively categorized into three groups according to treatment received: (i) medication only (n = 056), (ii) combined treatment (the initial medication treatment was switched to surgical treatment) (n = 32), and (iii) surgery only (n = 17). A prerequisite for inclusion in the study was use of BPH medication for at least half a year before the study (groups 1 and 2). These groups completed the International Prostate Symptom Score (IPSS) questionnaire at the start of BPH medical treatment (IPSS 1) and at the start of the trial (IPSS 2), and the staff calculated the difference (IPSS 1-IPSS 2 = Delta IPSS = DIPSS). All three groups provided demographic data (age, country of origin, education) and completed tri-dimensional personality questionnaires (TPQ) to measure three independent "temperament" personality dimensions to evaluate how different individuals feel or behave: novel seeking (NS), harm avoidance (HA), and reward dependence (RD). Data were analyzed using chi-square, t-test, one-way ANOVA and logistic regression. RESULTS: The choice of BPH treatment differed according to demographic variables and the RD dimension. CONCLUSIONS: Our study suggests that symptomatic BPH treatment is influenced less by the patient's personality and more by his life circumstances. Israeli-born patients were more conservative, Russian-born patients were ambivalent, and other foreign-born patients predominantly preferred surgical treatment. We assume that personality has a more decisive effect on patients with malignant disease and they accept the medical advice more easily. PMID- 26357721 TI - Assessment of Israeli Physicians' Knowledge, Experience and Attitudes towards Medical Cannabis: A Pilot Study. AB - BACKGROUND: Cannabis has been used throughout history for different purposes but was outlawed in the United States in 1937; many countries followed suit. Although recently reintroduced as a medical treatment in several countries, the use of cannabis in Israel is permitted for some medical purposes but is still controversial, eliciting heated public and professional debate. The few published studies on physicians' attitudes to medical cannabis found them to be generally unsupportive. OBJECTIVES: To examine, for the first time, the experience, knowledge and attitudes of Israeli physicians towards medical cannabis (MC). METHODS: A 32 item questionnaire reflected physicians' demographics, knowledge of and experience with MC and their attitudes to this treatment. RESULTS: Seventy two physicians participated in this study. Physicians generally agreed that MC treatment could be helpful for chronic and for terminally ill patients (n = 61, 79.2%). Oncologists and pain specialists did not agree unanimously that MC can undermine mental health, whereas other physicians did (P < 0.001, df = 4). Physicians who recommended MC in the past (once or more) agreed, more than physicians who did not, with the statement "MC treatment in Israel is accessible to patients who need it" (P < 0.05, df = 2). CONCLUSIONS: In contrast to other studies we found partial acceptance of MC as a therapeutic agent. Further in depth studies are needed to address regulatory and educational needs. PMID- 26357722 TI - Madura Foot or Philoctetes Foot? PMID- 26357723 TI - Air Pollution and Respiratory Morbidity in Israel: A Review of Accumulated Empiric Evidence. AB - Studies of the respiratory effects of air pollution in Israel published in peer reviewed journals have been infrequent. Most empiric evidence relates to the association between air pollution and childhood asthma; other air pollution effects on other illnesses are less thoroughly studied. Our evaluation provides a possible explanation for the quite contradictory results demonstrated in the various studies. Actual effect estimates appear to differ considerably, ranging from no air pollution effect to a reasonably strong association detected between PM10 and asthma. We attribute these discrepancies to different research methodologies and different types of data used in various studies. PMID- 26357724 TI - Food-Dependent Exercise-Induced Urticaria/Angioedema Caused by Lipid Transfer Protein in Two Children. PMID- 26357725 TI - Endovascular Treatment of Tonsillar Artery Pseudoaneurysm Causing Recurrent Hemorrhages after Tonsillectomy. PMID- 26357726 TI - Efficacy of Rituximab in Refractory Cold Agglutinin Hemolytic Anemia in a Patient with Ataxia-Telangiectasia. PMID- 26357727 TI - Intramyocardial Hemorrhage in a Young Adult. PMID- 26357728 TI - Mosaic Trisomy 14 in a Newborn with Multiple Malformations: When Chromosomal Microarray is a Clue to Diagnosis. PMID- 26357729 TI - Ring out the old, ring in the new. PMID- 26357730 TI - SELF ESTEEM AMONG 14-15 YEAR OLD GIRLS ON THE DECLINE. PMID- 26357731 TI - Association between increased LARC use and reduction in abortion. PMID- 26357732 TI - Midwife-led care 'safest' for low-risk second pregnancies. PMID- 26357733 TI - Health visitors 'not yet feeling benefit' of increased numbers. PMID- 26357734 TI - MyNHS to let patients compare care in England. PMID- 26357735 TI - Fatherhood Institute: supporting fathers to play their part. PMID- 26357736 TI - Maternal mental health. PMID- 26357737 TI - Getting published in COMMUNITY PRACTITIONER. PMID- 26357738 TI - School Nurse 121 Campaign. PMID- 26357739 TI - Health visitors' perceptions of barriers to health and wellbeing in European migrant families. AB - Since 2004 the population of European migrant workers and their families living in the UK has increased. In 2012 a small qualitative pilot study was conducted involving interviews with eight health visiting professionals working in a Merseyside borough in the north west of England. Health visitors were asked about their perceptions of barriers to health and wellbeing faced by European migrant families and common challenges experienced in practice. Interviews were analysed thematically and interpreted using a constructivist approach. Multiple perceptions emerged regarding migrant families'barriers to health and wellbeing; housing; language; and health service access, knowledge and attitudes. Health visitors provided confirmation of their important role within the public health agenda, identifying vulnerability and challenging inequalities particularly among minority ethnic and lower socio-economic groups. This study highlights areas for future consideration by public health and other agencies, particularly wider determinants of health and barriers in accessing health, public and community services. However, further quantitative and qualitative research is needed to investigate the needs, inequalities, service use and barriers to health and wellbeing experienced by European migrants. PMID- 26357740 TI - The positive impact of structured surfing courses on the wellbeing of vulnerable young people. AB - Involvement in positive leisure activities is a key way for young people to develop resilience and social and emotional skills. This paper outlines the evaluation of a six-week surfing intervention, the Wave Project, which aimed to boost wellbeing and confidence among 84 young people aged eight to 18, all of whom faced mental health issues or social exclusion. The intervention resulted in a significant and sustained increase in wellbeing. One year later, 70% of clients regularly attend a surf club and many have become trained as session volunteers. Parents and referrers noticed an increase in positive attitude and better communication, as well as improved self-management and behaviour at both home and school It is concluded that the Wave Project provides a demonstrable and cost effective way to deliver mental health care, mentoring and social integration of young people. Further service evaluation of accessibility and long-term outcomes is also recommended. PMID- 26357741 TI - Gypsies and Travellers: their history, culture and traditions. AB - Gypsies and Travellers living in Britain today are culturally diverse and made up of differing groups. The aim of this paper is to describe the different groups and sub-groups, and look at similarities and differences between these groups while highlighting the discrimination and prejudice experienced by the Travelling community as a whole. Although there is no one culture common to all these groups, they share an ancient tradition of 'nomadism' and an oral tradition of passing on knowledge. Gypsies and Irish Travellers are recognised as ethnic minorities under the Equality Act 2010 and it is estimated that there are between 200,000 and 300,000 living in the UK. This paper offers an account of how a specialist health visitor working in the south Gloucestershire area has attempted to reduce prejudice and discrimination experienced by Gypsies and Travellers by raising awareness of their cultural issues. It will also focus on how to ensure services take into account the needs of Gypsies and Travellers. PMID- 26357742 TI - Creating change in perinatal mental health. PMID- 26357743 TI - A health visiting sabbatical in South Sudan. PMID- 26357744 TI - Recognising meningitis in children. PMID- 26357745 TI - Support Health IT! PMID- 26357746 TI - Revving up for ICD-10 amid wheel-spinning. Just how are the coding enactment delays affecting revenue cycle? PMID- 26357747 TI - Should healthcare IT shoot for the cloud? PMID- 26357748 TI - Improve your organizational awareness. PMID- 26357749 TI - Embrace technology, get paid. Three factors impacting patient financial engagement and your bottom line. PMID- 26357750 TI - More doctors are feeling like robots. Ironically, technology can make it better. PMID- 26357751 TI - For this small practice, managing from the cloud is key. PMID- 26357752 TI - Data leads the way to solving patient throughput problems. an interview with Bill Griffith, MBA, CSSBB, CQA. PMID- 26357753 TI - Is middleware the right medicine? Doubt forms over HIEs and HL7, while real interoperability battles impact the OR. PMID- 26357754 TI - How to simplify practice management on the revenue cycle side. PMID- 26357755 TI - Bleeding green. PMID- 26357757 TI - Tight reins on IT purchases require awareness. Practice management involves more than EHR, EMR expertise. PMID- 26357756 TI - Horizon-scanning around HIPAA, HITECH. How far will they protect healthcare data from insiders, outsiders? PMID- 26357758 TI - Next-gen barcoding advances quality of care. Barcodes can protect the lives of patients from everyday errors. PMID- 26357759 TI - Get 'smart' about workstations. AB - The days of accessing patient health records via a clipboard and keeping drugs stored under simple lock and key are unceremoniously coming to a close. As healthcare IT paves the way toward a future run on data and interoperable systems, "smart" workstations are popping up in practices all over the world, streamlining workflow and creating a safer environment for clinician and patient alike. Health Management Technology talks with two of the leading manufacturers of automated systems and mobile workstations to discuss how they are changing the way providers and patients experience healthcare services. PMID- 26357760 TI - Don't let "visual hackers" invade your privacy. PMID- 26357761 TI - Integrate and automate RCM. How revenue cycle best practices helped one health system improve its financial performance. PMID- 26357762 TI - Improve patient revenue with analytics. PMID- 26357763 TI - Consider these four analytic integrations at the point of care for population health. PMID- 26357764 TI - Is communication population health's major pain point? PMID- 26357765 TI - ICD-10 preparations are not one size fits all. PMID- 26357766 TI - Achieving the Quadruple Aim. The Triple Aim is great, but there's something it leaves out. PMID- 26357767 TI - Cool Hand Juke. PMID- 26357768 TI - EHRs: Utility vs. futility. PMID- 26357769 TI - Virtualzation takes IT to the cloud. PMID- 26357770 TI - The only way to control BYOD is to embrace it. PMID- 26357771 TI - Bring your own device or bring your own disruption? How to handle the mulitude of challenges. PMID- 26357772 TI - Delivering proof of care at the point of care. How electronic visit verification can benefit clinicians, home health workers and patients. PMID- 26357773 TI - How self-service check-in works in the real world. Baptist Health CFO Katrina Belt gives the in- sider scoop on kiosk adoption and use by staff and patients. PMID- 26357774 TI - Looking in the ICD-10 rearview mirror. Did you take the right path? PMID- 26357775 TI - On-again, off-again may work for romance, but not Dr. Meeta Pancholi for ICD-10. A podiatrist comments on the effects of ICD-10 delays and testing. PMID- 26357776 TI - Data security in healthcare: Do you really know your vendors? PMID- 26357777 TI - How red flags, policies and technology can catch medical identity theft. PMID- 26357778 TI - Healthcare organizations lack tools for cyber situational awareness and threat assessment. PMID- 26357779 TI - You can't Band-Aid disaster preparedness. PMID- 26357780 TI - 10 key attributes of sustainability. PMID- 26357781 TI - The Rx for better care: Undistracted doctors. Assistive technologies hold the key.. PMID- 26357782 TI - Time Out. PMID- 26357783 TI - In Memorian. Remembrances of Maddie. PMID- 26357784 TI - Understanding Off-Label Use and Reference Blood Flows in Modern Membrane Oxygenators. AB - This editorial will address two issues that are still a source of global controversy and confusion in present day perfusion practice. Membrane oxygenators are designed and tested to a set of stringent flow standards prior to their release from every manufacturer. But how well do we know the iatrogenic consequences of pushing these devices beyond their maximum rated limits? In addition, how well do we know the meaning of the term 'AAMI Reference Flow' as it relates to the Manufacturers Maximum Rated Flow? PMID- 26357786 TI - Contemporary Oxygenator Design Relative to Hemolysis. AB - Hemolysis is a well-known phenomenon during cardiovascular surgery and generally attributed to cardiopulmonary bypass, particularly when using high-resistant oxygenators. This study aimed at investigating whether transoxygenator pressure drop can be considered an independent factor of hemolysis. Additionally, intraoxygenator blood distribution and shear stress were assessed. A low resistant (LR, n = 3), a moderate-resistant (MR, n = 3), and a high-resistant (HR, n = 3) clinically used membrane oxygenator were tested in vitro using a roller pump and freshly drawn heparinized porcine blood. Flow rates were set to 2 and 4 L/min and maximum flow compliant to the oxygenator type for 1 hour each. As a control, the oxygenator was excluded from the system. Blood samples were taken every 30 minutes for plasma-free hemoglobin assay and transoxygenator pressure was measured inline. Intraoxygenator blood distribution was assessed using an ultrasound dilution technique. Despite the relatively broad spectrum of pressure drop and resultant transoxygenator pressure drops (LR: 14-41 mmHg, MR: 29-115 mmHg, HR: 77-284 mmHg, respectively), no significant association (R2 = .074, p = .22) was found with the normalized index of hemolysis. The shear stress of each oxygenator at maximum flow rate amounted to 3.0 N/m2 (LR), 5.7 N/m2 (MR), and 8.4 N/m2 (HR), respectively. Analysis of blood flow distribution curves (kurtosis and skewness) revealed intraoxygenator blood flow distribution to become more homogeneous when blood flow rates increased. Contemporary oxygenators were shown not to be a predominant factor for red blood cell damage. PMID- 26357787 TI - Hemolysis-Associated Nitric Oxide Dysregulation during Extracorporeal Membrane Oxygenation. AB - Acute intravascular hemolysis during extracorporeal membrane oxygenation (ECMO) leads to increased levels of cell-free hemoglobin (FHb). Our aim was to investigate whether FHb levels are associated with nitric oxide (NO) consumption and clinical outcomes. A prospective observational study was performed involving pediatric patients on ECMO. Blood samples were collected before, during, and after the ECMO run, and plasma was evaluated for FHb, oxyhemoglobin, and NO consumption. Clinical data were collected including baseline patient characteristics, indications for ECMO, circuit changes, and mortality. Correlations between laboratory measures and associations between laboratory measures and clinical observations were evaluated. Twenty-three patients (11 male, 17 neonates) were enrolled with a median weight of 3.1 kg (interquartile range, 2.8-14.0 kg) and median ECMO run of 12 days (interquartile range, 5-19 day). There was a significant increase in FHb over time on ECMO (p = .007), and significant correlations were present between NO consumption and both FHb (r = .41, p = .01) and oxyhemoglobin levels (r = .98, p < .0001). Patients on ECMO for sepsis (n = 6) had lower average levels of oxyhemoglobin (mean [standard deviation {SD}] 14.5 [4.4] versus 19.0 [5.0] MUM, p = .07) and NO consumption (mean [SD] 15.8 [4.1] versus 19.8 [3.7] MUM, p = .04) during ECMO than patients with other indications. In the 3 days leading up to a circuit change, there were increases in mean total cell-free hemoglobin levels (24%/day, p = .08), oxyhemoglobin (37%/day, p = .005), and NO consumption (40%/day, p = .006) (n = 5). There were no significant associations identified between peak or average plasma measures of hemolysis and type of ECMO (venovenous versus venoarterial) or mortality. For children on ECMO, we observed a strong correlation between increased levels of plasma FHb and elevations in oxyhemoglobin and NO consumption; however, these changes were not associated with increased mortality. Increased hemolysis before circuit changes may be both a marker and a contributor to circuit failure. PMID- 26357785 TI - Attenuating the Systemic Inflammatory Response to Adult Cardiopulmonary Bypass: A Critical Review of the Evidence Base. AB - A wide range of pharmacological, surgical, and mechanical pump approaches have been studied to attenuate the systemic inflammatory response to cardiopulmonary bypass, yet no systematically based review exists to cover the scope of anti inflammatory interventions deployed. We therefore conducted an evidence-based review to capture "self-identified" anti-inflammatory interventions among adult cardiopulmonary bypass procedures. To be included, trials had to measure at least one inflammatory mediator and one clinical outcome, specified in the "Outcomes 2010" consensus statement. Ninety-eight papers satisfied inclusion criteria and formed the basis of the review. The review identified 33 different interventions and approaches to attenuate the systemic inflammatory response. However, only a minority of papers (35 of 98 [35.7%]) demonstrated any clinical improvement to one or more of the predefined outcome measures (most frequently myocardial protection or length of intensive care unit stay). No single intervention was supported by strong level A evidence (multiple randomized controlled trials [RCTs] or meta-analysis) for clinical benefit. Interventions at level A evidence included off-pump surgery, minimized circuits, biocompatible circuit coatings, leukocyte filtration, complement C5 inhibition, preoperative aspirin, and corticosteroid prophylaxis. Interventions at level B evidence (single RCT) for minimizing inflammation included nitric oxide donors, C1 esterase inhibition, neutrophil elastase inhibition, propofol, propionyl-L-carnitine, and intensive insulin therapy. A secondary analysis revealed that suppression of at least one inflammatory marker was necessary but not sufficient to confer clinical benefit. The most effective interventions were those that targeted multiple inflammatory pathways. These observations are consistent with a "multiple hit" hypothesis, whereby clinically effective suppression of the systemic inflammatory response requires hitting multiple inflammatory targets simultaneously. Further research is warranted to evaluate if combinations of interventions that target multiple inflammatory pathways are capable of synergistically reducing inflammation and improving outcomes after cardiopulmonary bypass. PMID- 26357788 TI - Effect of New Heparin Potency on Activated Clotting Time during Pediatric Cardiac Surgery: A Retrospective Chart Review. AB - In 2009, the U.S Food and Drug Administration (FDA) announced a two-phase change in unfractionated heparin to reduce contamination and create a new potency reference. The FDA announced the change would bring about a 10% decrease in potency from the old heparin (OH) to new heparin (NH). The purpose of this article is to compare heparin in pediatric patients undergoing cardiac surgery before and after the FDA changes. After Institutional Review Board approval, a retrospective chart review was conducted with pediatric patients (n = 266) undergoing cardiac surgery. All patients received a heparin loading dose of 400 IU/kg and data collected included patient demographics, baseline activated clotting time (ACT), ACT after initial heparin dose, and heparin dose-response. These data were then further broken down into age blocks consisting of neonates (< 1 month), 1-12 months, 1-5 years old, and older than 5 years old. In 17.3% of cases in the NH group, the ACT after the initial heparin dose did not reach the critical value of 400 seconds necessary for initiation of cardiopulmonary bypass (CPB). This is significantly higher than the 8.9% of cases in the OH group (p < .05). There was an overall trend among age groups that the NH was less potent than OH. However, only the 1-5 years of age group showed significance at p < .05. Given the median ACTs 591 seconds for OH and 484 seconds for NH, the calculated percentage difference was 18.1%. The results from this retrospective pediatric chart review indicate that the change in heparin potency greatly deviates from the 10% change reported by the FDA. In conclusion, NH has a trend of lower potency and frequent monitoring is necessary to maintain a safe level of anticoagulation during CPB. PMID- 26357789 TI - Air Transmission Comparison of the Affinity Fusion Oxygenator with an Integrated Arterial Filter to the Affinity NT Oxygenator with a Separate Arterial Filter. AB - Arterial filters used in the extracorporeal circuit (ECC) have been shown to minimize cerebral injury by capturing particulate matter and microbubbles. We clinically use the Affinity NT oxygenator with an Affinity arterial filter attached ("Affinity system"). The new Affinity Fusion oxygenator ("Fusion") incorporates integrated arterial filtering. Our aim was to determine if the Fusion oxygenator was as safe as the Affinity system in terms of relative microbubble transmission of introduced air. A recirculating in vitro circuit primed with blood was used to compare the Fusion with the Affinity system. Microbubbles were detected using a GAMPT BC100 Doppler in the oxygenator-arterial filter outflow line. Measurements were taken 1 minute before and 3 minutes after bolusing 30 mL air proximal to the venous reservoir while altering pump flow rates (3 L/min; 5 L/min). Both the Fusion and Affinity system transmitted microbubbles during air injection. Microbubble volume transmitted at 5 L/min pump flow was significantly greater than at 3 L/min in both systems. The Fusion tended to transmit fewer bubbles, less bubble volume, and smaller sized bubbles than the Affinity system. Under the parameters of this in vitro study, the Affinity Fusion oxygenator with an integrated arterial filter is as safe as the Affinity NT oxygenator with a separate arterial filter in terms of microbubble transmission. However, more research is needed to confirm this study's findings and generalizability to the clinical environment. As both oxygenator-arterial filter systems transmitted microbubbles during air introduction, it is important to develop strategies to minimize microbubble entry into the ECC. PMID- 26357790 TI - Sequential Blood Filtration for Extracorporeal Circulation: Initial Results from a Proof-of-Concept Prototype. AB - Micropore filters are used during extracorporeal circulation to prevent gaseous and solid particles from entering the patient's systemic circulation. Although these devices improve patient safety, limitations in current designs have prompted the development of a new concept in micropore filtration. A prototype of the new design was made using 40-MUm filter screens and compared against four commercially available filters for performance in pressure loss and gross air handling. Pre- and postfilter bubble counts for 5- and 10-mL bolus injections in an ex vivo test circuit were recorded using a Doppler ultrasound bubble counter. Statistical analysis of results for bubble volume reduction between test filters was performed with one-way repeated-measures analysis of variance using Bonferroni post hoc tests. Changes in filter performance with changes in microbubble load were also assessed with dependent t tests using the 5- and 10-mL bolus injections as the paired sample for each filter. Significance was set at p < .05. All filters in the test group were comparable in pressure loss performance, showing a range of 26-33 mmHg at a flow rate of 6 L/min. In gross air-handling studies, the prototype showed improved bubble volume reduction, reaching statistical significance with three of the four commercial filters. All test filters showed decreased performance in bubble volume reduction when the microbubble load was increased. Findings from this research support the underpinning theories of a sequential arterial-line filter design and suggest that improvements in microbubble filtration may be possible using this technique. PMID- 26357791 TI - Cardiopulmonary Bypass in a Patient with Factor XII Deficiency. AB - The performance of cardiopulmonary bypass (CPB) in the factor XII-deficient patient is challenging in that the normal method for monitoring anticoagulation is ineffective as a result of an impaired contact activation system. We report the case of a factor XII-deficient patient who underwent surgical revascularization on CPB. His factor XII level was replenished with fresh-frozen plasma immediately before surgery. This management strategy lowered the baseline activated clotting time (ACT) to near normal, providing a meaningful ACT value for CPB. Factor XII is also a key component in the fibrinolytic system and its deficiency is associated with increased thrombosis. Because the factor XII level quickly returns to baseline postoperatively, perioperative care must include strategies to avoid postoperative thromboembolic events. PMID- 26357792 TI - Factor XII Deficiency and Cardiopulmonary Bypass. AB - Factor XII deficiency is a laboratory finding in patients who normally do not present with bleeding tendencies. This deficiency is important in the patient undergoing cardiopulmonary bypass because activated clotting times are not helpful in determining proper levels of heparin anticoagulation and its reversal. We present a case of a patient with factor XII deficiency that had coronary artery bypass grafting and cardiopulmonary bypass using heparin for anticoagulation. Cardiopulmonary bypass was successfully carried out by monitoring heparin concentration ensuring adequate heparinization during the procedure. Results from activated clotting time, heparin dose-response, and heparin protamine titration are given. Heparin anticoagulation in patients with factor XII deficiency can be safely carried out with heparin concentration monitoring. PMID- 26357793 TI - An Evaluation Trial of The National Perfusion Registry. AB - The International Consortium for Evidence-Based Perfusion (ICEBP) is a collaborative group whose mission is to improve, continuously, the delivery of care and outcomes for patients undergoing cardiac surgery. To achieve this end, the ICEBP supports the development of perfusion registries to evaluate clinical practices and has established evidence-based guidelines for perfusion. The Japanese Society of Extra-Corporeal Technology in Medicine (JaSECT) developed a perfusion registry to examine variation in perfusion practice in Japan. A pilot study was designed to determine the rate and accuracy of data extraction from patients' medical records and perfusion practice records and the subsequent entry of data into the registry form. We designed an input matching test using medical records and perfusion records from a sample of patients. Five institutions participated in data. extraction and entry from 10 randomly selected case records. Perfusionists entered data in the registry form in accordance with the instruction manual prepared by the JaSECT guideline committee. The time taken to input every case in the registry was measured. An interview-based survey was carried out across institutions after the completion of the pilot. The time required for data entry stabilized after approximately five cases to a rate that was 40% of the first case entry time. Data entered into the registry by perfusionists for multiple-choice items were accurate 65% of the time and accurate 25% of the time for numerical data. The interview-based survey identified a total of 38 opportunities for improvement in the input form and 58 recommended changes for the instruction manual. The accuracy of data may be improved by developing a method allowing the objective detection of deficient data when present in the perfusion case record by developing automatic data acquisition from the automatic perfusion recording system currently in use, and by changing as many numerical value input items as possible to multiple-choice items. PMID- 26357794 TI - Using Zero Balance Ultrafiltration with Dialysate as a Replacement Fluid for Hyperkalemia during Cardiopulmonary Bypass. AB - Avoiding or managing hyperkalemia during cardiac surgery, especially in a patient with chronic renal insufficiency, can be challenging. Hyperkalemic cardioplegia solution is usually administered to achieve and maintain an electrical arrest of the heart. This solution eventually mixes in with the systemic circulation, contributing to elevated systemic potassium levels. Administration of packed red blood cells, hemolysis, tissue damage, and acidosis are also common causes of hyperkalemia. Current strategies to avoid or manage hyperkalemia include minimizing the volume of cardioplegia administered, shifting potassium from the extracellular into the intracellular space (by the administration of sodium bicarbonate when the pH is low and/or dextrose-insulin when effects relatively independent of serum pH are desired), using zero-balanced ultrafiltration (Z-BUF) with normal saline as the replacement fluid (to remove potassium from the body rather than simply shift the electrolyte across cellular membranes), and, occasionally, hemodialysis (1). We report the application of Z-BUF using an electrolyte-balanced, low potassium dialysate solution rather than isotonic saline to avoid a high chloride load and the potential for hyperchloremic acidosis to successfully treat hyperkalemia while on cardiopulmonary bypass. PMID- 26357795 TI - An Unusual Case of Cannula Obstruction Resulting from Venous Thromboembolism. AB - Cerebral strokes of unknown origin frequently present with a patent foramen ovale (PFO), a common atrial septal defect occurring in approximately 25% of the adult population. Deep vein thrombosis (DVT) or pulmonary embolism (PE) in the presence of a PFO can produce paradoxical systemic embolization subsequent to an increase in pulmonary pressure, permitting entry of thrombi into the arterial circulation. Diagnosis of an impending paradoxical embolism (IPDE) involves the detection of DVT or PE in the presence of an abnormal communication between left and right circulations and may include a right-to-left shunt. Treatment includes oral anticoagulation, antiplatelet agents, thrombolysis, transcatheter closure of the defect, or surgical embolectomy and PFO closure. As a result of risks of intracranial hemorrhage with fibrinolysis, pulmonary embolectomy using cardiopulmonary bypass (CPB) and deep hypothermia is a primary treatment with a surgical mortality rate at approximately 5%. Despite optimal management, IPDE is associated with a mortality rate of 18%. Prompt diagnosis and treatment is critical in avoiding systemic thromboembolization and strokes in these patients. We report a case of superior vena cava cannula obstruction resulting from a paradoxical embolus traversing a PFO during surgery. Warning signs and management during CPB are discussed. PMID- 26357796 TI - Impact of Device Standards on Perfusion Practice. PMID- 26357797 TI - A 2013 Survey on Pressure Monitoring in Adult Cardiopulmonary Bypass Circuits: Modes and Applications. AB - Pressure data acquired from multiple sites of extracorporeal circuits can be an important parameter to monitor for the safe conduct of cardiopulmonary bypass (CPB). Although previous surveys demonstrate that CPB circuit pressure monitoring is widely used, there are very little data cataloging specific applications of this practice. Therefore, the purpose of this study is to survey the perfusion community to catalog 1) primary CPB circuit site pressure monitoring locations; 2) type of manometers used; 3) pressure monitoring interface and servoregulation with pump console; and 4) the rationale and documentation associated with pressure monitoring during CPB. In June 2013, a validated 27-question online survey was sent directly through an e-mail link to the chief perfusionists in the northeast United States. Completed surveys were received from 75 of 117 surveys deployed yielding a 64% response rate. Arterial line pressure monitoring during CPB is reported by 99% with six distinct circuit site locations identified. Cardioplegia system pressure was monitored by 95% of the centers. For vacuum assisted venous drainage (VAVD) users, the venous pressure was measured by 72% of the responding centers. Arterial line pressure servoregulation of the arterial pump was indicated by 61% of respondents and 75% of centers record arterial line pressure in their perfusion record. Most centers (77%) report the use of a transducer that is integrated into the pump console providing a digital pressure display, whereas 20% combine an aneroid gauge manometer with the integrated digital transducer. This study demonstrates that the practice of arterial line pressure monitoring during CPB is nearly universal. However, the selection of the pressure monitoring site on the circuit, modes of monitoring pressure, and their applications are highly variable across the perfusion community. PMID- 26357798 TI - Influence of Two Colloidal Extracorporeal Primes on Coagulation of Cardiac Surgical Patients: A Prospectively Randomized Open-Label Pilot Trial. AB - The search for the ideal priming fluid continues as more evidence is discovered about side effects of volume expanders. With the availability of modern, balanced hydroxyethyl starch (HES) solutions with less side effects than former HES solutions, we considered to replace our gelatin- (modified gelatin) based extracorporeal circuit prime for a HES (130/.42) prime. Therefore, we studied the influence of two colloidal priming fluids on postoperative coagulation in patients undergoing cardiac surgery. The primary endpoint was to compare clot formation time between the HES group and the gelatin group with rotational thromboelastometry (ROTEM). Additionally we compared colloid osmotic pressure and fluid balance of both groups. Forty patients, undergoing elective first time coronary artery bypass grafting or single-valve surgery, were included in this prospectively randomized open-label pilot study. Laboratory data and ROTEM data were collected and analyzed for differences between the two groups. ROTEM data show significantly more prolongation in Extem clot formation time and significant more decrease in Extem alpha in the HES group. Fibtem maximum clot firmness was significantly smaller in the HES group; this was consistent with fibrinogen concentration measurement, which decreased more in the HES group than in the gelatin group and recovered more over time in the gelatin group. We found no significant difference in colloid. osmotic pressure between the groups. In this trial, HES (130/.42) impairs coagulation significantly more compared with gelatin. These differences in influence on coagulation did not lead to a difference in blood loss or fluid balance, so clinical relevance could not be proven. PMID- 26357799 TI - Interdisciplinary Simulation Using the Cardiopulmonary Bypass Simulator (CPBS)? AB - Interdisciplinary education offerings between students of cardiovascular science and nurse anesthesia are uncommon despite the collaborative nature of these disciplines. The dual purpose of this article is to describe a method for interdisciplinary simulation and to report survey responses provided by participants. An interdisciplinary simulation session using concurrent use of the cardiopulmonary bypass simulator and the emergency care simulator is described. Interdisciplinary perceptions before and after the event were surveyed using the revised Interdisciplinary Education Perception Scale. Statistically significant differences between baseline and final survey responses were observed in the total score and within the areas of competency and perception of cooperation. Emerging simulation technologies and novel combinations of existing devices can facilitate meaningful interdisciplinary educational opportunities for health science students. PMID- 26357800 TI - The Need to Develop Standardized Protocols for the Timing of Extracorporeal Membrane Oxygenation Initiation among Adult Patients in Cardiac Arrest: A Case Study. AB - The duration of time between cardiac arrest, cardiopulmonary resuscitation (CPR), and initiation of extracorporeal membrane oxygenation (ECMO) among refractory patients is correlated with mortality. The duration of conventional CPR (CCPR) beyond which ECMO support should not be offered due to poor outcomes is not established. This case study describes a patient with heart failure with recurrent episodes of ventricular tachycardia who had a witnessed cardiac arrest in a coronary care unit. The patient received approximately 45 minutes of CCPR. Venoarterial ECMO was then initiated for extracorporeal CPR (ECPR) support. The total recorded ischemic time between CCPR and ECPR was 60 minutes. Despite aggressive medical therapy, ECMO support was discontinued 48 hours later following absence of electroencephalographic activity and no evidence of cardiac function ultimately leading to the patient's death. This case study illustrates the possibility that prolonged ischemia resulting from duration of CCPR and time to initiate ECPR may contribute to adverse clinical outcomes. Systems of care that might reduce delays in ECMO initiation and improve patient outcomes are discussed including: 1) development of standardized protocols to allow for rapid initiation of ECMO support; 2) systematic evaluation of parameters such as biomarkers that might identify patients at risk for cardiac arrest in settings where ECMO is readily available; and 3) assessment of patient criteria to define subsets of individuals among whom late institution of ECMO, an expensive and labor-intensive mode of circulatory support, might be futile. PMID- 26357801 TI - Successful Management of Thrombosis of the Proximal Aorta after Implantation with a Biventricular Assist Device. AB - Continuous-flow ventricular assist devices (CVADs) are associated with a significant complication profile that includes thrombosis of the ascending aorta and aortic valve, thromboembolism, and stroke. Despite an increasing number of reports of thromboembolic complications related to CVADs, there is little in the literature to guide their management. This report describes successful management strategies used during two cases of thrombosis of the ascending aorta during biventricular CentriMag (Levitronix LLC, Waltham, MA) support, including using pre-existing cannulas to initiate cardiopulmonary bypass. PMID- 26357802 TI - Failure of Intraoperative Red Cell Salvage: A Patient with Sickle Cell Disease and HELLP (Hemolysis, Elevated Liver enzymes and Low Platelets) Syndrome. AB - Cell salvage is a process whereby the bloodshed from the operative field is collected and returned to the patient. It can be especially useful when allogeneic red blood cell (RBC) units are not readily available such as when the recipient has multiple alloantibodies. We report on the anesthesia and transfusion strategies for managing a pregnant patient with sickle cell disease (SCD) with HELLP (Hemolysis, Elevated Liver enzymes and Low Platelets) syndrome. A pregnant patient with twins at 30 weeks of gestation was admitted in an SCD crisis. She subsequently developed HELLP syndrome and required urgent cesarean delivery; however, she had multiple RBC antibodies complicating the immediate provision of cross-matched RBC units. Cell salvage was used to capture the blood shed during her procedure while the blood bank was searching for compatible RBCs units. Despite multiple interventions designed to optimize the cell salvage procedure for the unique challenges of a patient with SCD, the salvaged RBCs hemolyzed and could not be reinfused. Cell salvage in an obstetric patient with SCD in an acute crisis and super-imposed HELLP was unable to recover intact and useable RBCs. Further studies into methods of optimizing the procedure for use in this context are warranted. Close communication between the clinical teams treating the patient and the transfusion service is required so that the RBC transfusion requirements can be anticipated; this is especially important when the patient has multiple antibodies. PMID- 26357803 TI - Use of del Nido Cardioplegia for Adult Cardiac Surgery at the Cleveland Clinic: Perfusion Implications. AB - Cardiac arrest by cardioplegia provides a reproducible and safe method to induce and maintain electromechanical cardiac quiescence. Techniques of intraoperative myocardial protection are constantly evolving. For the past three decades, modified Buckberg cardioplegia solution has been used for adult cardiac surgery at the Cleveland Clinic. This formulation serves as the crystalloid component, which is delivered 4:1 with oxygenated patient's blood to crystalloid. Meanwhile, our use of the del Nido cardioplegia solution in adult patients, heretofore primarily used in pediatric cardiac surgical centers, has been increasing over the past several years. Single-dose, cold blood del Nido cardioplegia can be delivered antegrade if the duration of the operation will be limited and if there is no significant coronary artery disease or aortic insufficiency that would limit the distribution of cardioplegia. The addition of del Nido cardioplegia to our cardioplegia armamentarium allows us to customize our myocardial protection strategies for different surgical needs. This article aims to provide information on technical aspects of del Nido cardioplegia in adult cardiac surgery and its use at the Cleveland Clinic in the adult surgical population. PMID- 26357805 TI - Response to Letter "A Single Entry Level into the Perfusion Profession is Not the Solution" by Colligan and Patel. PMID- 26357804 TI - A Single Entry Level into the Perfusion Profession is Not the Solution. PMID- 26357806 TI - President's Perspective. PMID- 26357807 TI - CAT OF THE MONTH. Preemptive Nonsteroidal Anti-inflammatory Drugs Increases the Success Rate of Inferior Alveolar Nerve Blocks in Mandibular Posterior Teeth with Symptomatic Irreversible Pulpitis UT CAT #2807. PMID- 26357808 TI - Oral and Maxillofacial Pathology. Case of the Month. Primary Syphilis. PMID- 26357809 TI - Texas First Dental Home: A Snapshot after Five Years. AB - BACKGROUND: Early caries is still the most prevalent disease of childhood. Its incidence continues to be high, despite recent progress in the amount of untreated caries. The disease is more prevalent in low socio-economic and minority groups. To address this issue, in 2008 Texas implemented the First Dental Home Program for Medicaid children from 6 to 35 months old. The program consists in providing up to 10 preventive and oral health education visits to children very early in life. A specific dental visit code and a bundled payment of $94 were offered to insure adequate dental provider participation. Little is known about the program results to date. This paper evaluates program development at 5 years. METHODS: Two data sets on first dental home patients and providers were obtained from the Texas Department of Health Services. The data cover a 5 year period (3rd quarter of 2008 to end of 2nd quarter 2013). Program participants were geocoded and their distribution was compared to dental underserved areas. Program uptake over time and the relationship between provider and patient locations were also evaluated. RESULTS: The program covered 440,191 children between September 1st, 2011 and February 28th, 2013. All but two counties in Texas had at least one patient enrolled in the program. As expected, program uptake was higher in highly populated and economically disadvantaged counties. Forty-five percent of Texas licensed dentists participated in the program. The number of dental providers certified to provide first dental home services was highly correlated with the number of patients enrolled in the program (r = 0.893). The number of children participating in the program was between 20.4% and 23%. 29.7% of the first dental home patients had only one visit while only 17.1% had five or more visits. The number of patients and the number of visits per patient peaked at the end of 2011 and flatten thereafter. CONCLUSION: Many children benefited from the program since its rollout. However, despite considerable financial resources and dental provider participation, the uptake of the first dental home program by Medicaid beneficiaries could be improved. Moreover, those who participate do not always take full advantage of the program. Without adequate participation, the desired outcomes of the program may not materialize. Additional efforts to catalyze program development and on going evaluation may be needed. PMID- 26357810 TI - Collaborative Practice--Paving the Path to Success. PMID- 26357811 TI - Autonomy and Agency. PMID- 26357812 TI - Dentistry for the Ages: Part II. PMID- 26357813 TI - The Seattle Care Pathway: Defining Dental Care for Older Adults. AB - It is well-recognized that the demographic shift in the population will result in a larger proportion of older adults and those adults will live longer than ever before. There is, therefore, a need to ensure dental services recognize this transition and plan for the management of older adults in primary care dental practices. This article describes the evidence for, and the details of, the Seattle Care Pathway to ensure older adults receive optimum dental care. PMID- 26357814 TI - Root Caries in Older Adults. AB - Older adults are retaining an increasing number of natural teeth, and nearly half of all individuals aged 75 and older have experienced root caries. Root caries is a major cause of tooth loss in older adults, and tooth loss is the most significant negative impact on oral health-related quality of life for the elderly. The need for improved preventive efforts and treatment strategies for this population is acute. PMID- 26357815 TI - Aging Periodontium, Aging Patient: Current Concepts. AB - A functioning natural dentition is essential to maintaining overall health in the elderly patient. While age-related alterations in periodontal tissues and the immune system may make an elderly patient more susceptible to periodontal breakdown, age itself is not a major risk factor for periodontal diseases. Rather, individual age-associated factors such as systemic diseases, medications and changes in behavior, motor function and cognitive function should be considered for each elderly patient when making treatment decisions. PMID- 26357816 TI - Apple Tree Dental: An Innovative Oral Health Solution. AB - The Surgeon General's Report on Oral Health called attention to the "silent epidemic" of dental disease. Older adults and other vulnerable people continue to suffer disproportionately from dental disease and inadequate access to care. As a society and as dental professionals, we face multiple challenges to care for our aging patients, parents and grandparents. Apple Tree Dental's community collaborative practice model illustrates a sustainable, patient-centered approach to overcoming barriers to care across the lifespan. PMID- 26357817 TI - Accounting Controls Can Prevent Dishonest Behavior. PMID- 26357818 TI - Marketing and Advertising Rules. PMID- 26357819 TI - Aging Gracefully (and Other Indignities). PMID- 26357820 TI - From Path to Clover.... Life Lessons on my Holistic Journey. PMID- 26357821 TI - Presence along the Journey: Caring for Cancer Patients at End-of-Life. PMID- 26357822 TI - The Village is Here: A Community Approach to Cancer Care. PMID- 26357823 TI - Nursing Knowledge & Integrative Therapies in the Oncology Setting. PMID- 26357824 TI - Integrative & Holistic Oncology Nursing. PMID- 26357825 TI - Yoga and Nursing in Cancer Care. PMID- 26357826 TI - SHENG ZHEN GONG: A Heart-Centered Meditation Practice to Promote Wellness for Oncology Caregivers. PMID- 26357827 TI - STEMIs and Other Sources of Chest Pain. It looks like another MI for this heart patient--but what's different?. PMID- 26357828 TI - Do You Work for a Dysfunctional EMS Agency? Leadership may be the problem, but here's what you can do about it. PMID- 26357829 TI - Heads-Up CPR: Can It Improve Outcomes? A new twist on an old method has some top docs excited. PMID- 26357830 TI - CASE STUDY: COMBATIVE CARDIAC PATIENT. What do you do when a patient regains consciousness during mechanical CPR?. PMID- 26357831 TI - CASE STUDY: ACUTE ISOLATED POSTERIOR STEMI. The ST depression of cardiac ischemia doesn't localize to a particular myocardial territory. PMID- 26357832 TI - Resuscitation on the Fireground: Prevention, Recognition and Response. PMID- 26357833 TI - How to Build Better Systems of Care. PMID- 26357834 TI - Providers Selection & Training for MIH-CP Programs. PMID- 26357835 TI - Selective Service. You're not doing the public a favor by answering its calls for help. PMID- 26357837 TI - Indium(III) Chloride-Catalyzed Isocyanide Insertion Reaction to Construct Complex Spirooxindole. AB - An unusual multiple isocyanide insertion reaction with methyleneindolinone using indium(III) chloride as the catalyst has been disclosed. This strategy allows for the rapid construction of structurally complex spirooxindole in an efficient manner. The present protocol features mild conditions, atom economy, and broad substrate scope. PMID- 26357836 TI - Spinal anaesthesia at low and moderately high altitudes: a comparison of anaesthetic parameters and hemodynamic changes. AB - BACKGROUND: Hypoxemia caused high altitude leads to an increase and variability in CSF volume. The purpose of this prospective study was to detect the differences, if any, between moderately highlanders and lowlanders in terms of anaesthetic parameters under neuroaxial anaesthesia. METHODS: Consecutive patients living at moderately high altitude (Erzurum, 1890 m above the sea level) and sea level (Sakarya, 31 m above the sea level) scheduled for elective lower extremity surgery with spinal anaesthesia were enrolled in this study (n = 70, for each group). Same anaesthesia protocol was applied for all patients. Spinal anaesthesia was provided with hyperbaric bupivacaine 0.5 %, 9 mg (1.8 mL) in all patients. Anaesthetic characteristics and hemodynamic parameters of patients were recorded. The findings obtained in two different altitudes were compared using appropriate statistical tests. If data was not normally distributed, comparisons were determined using the Mann-Whitney U-test. Comparisons were determined using the Independent T test when data was normally distributed and Fisher's exact test was used to compare the percentage values. RESULTS: Duration of the block procedure (minutes) was significantly shorter at the sea level (14.34 +/- 0.88) than at moderate altitude (20.38 +/- 1.46) (P < 0.001). Motor block duration (minutes) was higher at the sea level compared to the moderate altitude (310.2 +/ 104.2, 200.4 +/- 103.2; respectively; P < 0.05). Also, the sensory block time (minutes) was higher at the sea level compared to moderate altitude (200.2 +/- 50. minutes vs. 155.2 +/- 60.7 min; respectively; P < 0.05). Moderate altitude group had significantly higher MABP values at baseline, during surgery and at postoperative 1(st) and 2nd hours than in the sea level group (P < 0.05, for all). Moderately high altitude group had lower heart rate values at baseline, during surgery and postoperative 1(st) and 2(nd) hours compared with the sea level group (P < 0.05). PDPH was seen more frequently (7.14 vs. 2.85 %; P < 0.05) at moderate altitude. CONCLUSIONS: Hemodynamic variations and more anaesthetic requirements following the spinal anaesthesia may be observed at moderately high altitudes compared to the sea level. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12614000749606 . PMID- 26357838 TI - The distribution of jhp0940, jhp0945, jhp0947, jhp0949 and jhp0951 genes of Helicobacter pylori in China. AB - BACKGROUND: The plasticity region of Helicobacter pylori (H. pylori) is a large chromosomal segment containing strain-specific genes. The prevalence of the plasticity region genes of the H. pylori strains in China remains unknown. The aim of this study was to examine the status of these genes and to assess the relationship between the genes and the diseases caused by H. pylori infection. METHODS: A total of 141 strains were isolated from patients with chronic active gastritis (CAG), peptic ulcer disease (PUD) and gastric carcinoma (GC). The prevalence of jhp0940, jhp0945, jhp0947, jhp0949 and jhp0951 was determined using PCR, and the results were analyzed using the chi-squared test. RESULTS: The prevalence rates of jhp0940, jhp0945, jhp0947, jhp0949 and jhp0951 in the H. pylori strains were 42.55, 51.06, 20.57, 56.03 and 63.12%, respectively. The prevalence rates of jhp0940 were similar in the isolates from the CAG, PUD and GC patients, and there was no association between the jhp0940 status and any of the diseases. In contrast, the prevalence rates of jhp0945, jhp0947, jhp0949 and jhp0951 were significantly higher in the PUD and GC isolates than in the CAG isolates (p < 0.01). A univariate analysis showed that jhp0945, jhp0947, jhp0949 and jhp0951 increased the risk of PUD, while only jhp0951 was significantly associated with PUD in the multivariate analysis (p = 0.0149). The jhp0945 positive isolates were significantly associated with an increased risk for GC (p = 0.0097). CONCLUSION: The plasticity region genes are widely distributed in Chinese patients, and a high prevalence of these genes occurs in more serious diseases. Therefore, jhp0951 status is an independent factor associated with the development of PUD, and jhp0945 may predict the future development of GC in patients with CAG and is considered to be the best candidate disease marker for H. pylori-related diseases. PMID- 26357839 TI - Carbonic anhydrase IX inhibition is an effective strategy for osteosarcoma treatment. AB - OBJECTIVE: Hypoxia-inducible factor 1, a regulator of CA IX activity, is often overexpressed in human osteosarcoma (OS) but not in normal tissues, and its expression levels correlate with prognosis. In this study, we investigated the therapeutic potential of newly synthesized CA IX sulfonamide inhibitors in OS. METHODS: CA IX expression was evaluated in OS cell lines and bone marrow stromal cells (BMSC). After treatment with CA IX inhibitors, cell proliferation, apoptosis, cell cycle, extracellular and cytosolic pH changes were evaluated both in vitro and in mouse OS xenografts. RESULTS: CA IX expression levels were significantly higher in OS than in BMSC. Accordingly, CA IX inhibitor 3 induced remarkable cytotoxicity on OS cells without affecting BMSC proliferation. This activity was increased under hypoxia, and was mediated by cell cycle arrest and by the modulation of cytosolic and extracellular pH. In vivo, CA IX inhibitor 3 reduced tumor growth by inducing significant necrosis. CONCLUSIONS: Our results provide a strong rationale for the clinical use of the newly synthesized CA IX inhibitor 3 in human OS. PMID- 26357840 TI - CRISPRing into the woods. AB - The CRISPR/Cas9 technology is a welcome breakthrough for genome editing, owing to its precision, efficiency, versatility and ease of adoption. We recently reported the first application of CRISPR/Cas9 for biallelic mutations in stably transformed Populus, extending the species range of this powerful technology to woody perennials. An underappreciated obstacle in genome editing of outcrossing species is the frequent occurrence of sequence polymorphisms that can render CRISPR/Cas9 unproductive. We discuss experimental evidence as well as genome-wide computational analysis to demonstrate the sensitivity of CRISPR/Cas9 to allelic heterozygosity, and highlight tools and strategies that can help deal with such sequence polymorphisms. With its specificity, CRISPR/Cas9 offers a less equivocal means than previous approaches for discerning functional redundancy of paralogous genes that are prevalent in plant genomes. Continuing improvements of the CRISPR/Cas9 system for multiplex genome engineering should facilitate these efforts. The paradigm shift brought about by CRISPR/Cas9 promises to accelerate not only basic research but also applied crop improvement progress. PMID- 26357841 TI - Pseudoperipheral palsy: a case of subcortical infarction imitating peripheral neuropathy. AB - BACKGROUND: Vascular damage in the central hand knob area can mimic peripheral motor nerve deficits. CASE PRESENTATION: We describe the case of a woman presenting with apparent peripheral neuropathy. Brain magnetic resonance imaging and computed tomography angiography revealed an infarct in the precentral hand knob area, with significant stenosis in the right proximal middle cerebral artery trunk. Subsequent 3-Tesla magnetic resonance imaging of the brain suggested cerebral angiitis. The patient experienced improved hand function following combined glucocorticoid and cyclophosphamide treatment. CONCLUSION: Vascular damage in the hand knob area should be considered when evaluating peripheral motor nerve deficits in the presence of normal nerve conduction velocities. The diagnosis of cerebral angiitis remains a major challenge for clinicians. PMID- 26357843 TI - Resistance of Rice Varieties to the Stored-Product Insect, Sitophilus zeamais (Coleoptera: Curculionidae). AB - Four common Portuguese rice varieties--Thaibonnet, Gladio, Albatros, and Eurosis- were tested for their relative susceptibility to Sitophilus zeamais Motschulsky, a common pest of stored rice in Portugal and in tropical countries. Physical (moisture content, hardness, length, and width) and chemical (by attenuated total reflection-Fourier transform infrared spectroscopy) properties of rice kernels were measured. Insect bioassays measured median developmental time, Dobie's index of susceptibility, percentage of damaged grains and weight loss, and progeny developed. This was done for paddy, brown rice, and polished rice for each variety. There were small, but significant, differences in insect resistance among the varieties. However, it was different for paddy and polished rice. In paddy, these differences were correlated with hull damage, and Eurosis was the most susceptible variety. In polished rice, resistance was correlated with hardness, and Thaibonnet was the most susceptible variety. In general, paddy rice was more resistant to insect attack, followed by polished rice and then brown rice. Paddy kernels selected with undamaged hull were completely resistant to attack. Implications for IPM and breeding for resistant varieties are discussed. PMID- 26357844 TI - Comparative Life Histories of Greenbugs and Sugarcane Aphids (Hemiptera: Aphididae) Coinfesting Susceptible and Resistant Sorghums. AB - Host-plant resistance has been a fundamental component of aphid management in cereal crops. Over decades, various sources of resistance to greenbug, Schizaphis graminum (Rondani), were bred into cultivars of sorghum, Sorghum bicolor (L.) Moench, to counter recurring virulent greenbug biotypes. The recent invasion of sugarcane aphid, Melanaphis sacchari (Zehntner), raised questions about plant mediated interactions between the two aphids and the possibility of using greenbug antibiosis against sugarcane aphid. The present work was undertaken to characterize the impact of PI 550610 resistance to 'biotype I' greenbug, expressed in seed parental line KS 116B, on aphid life histories and to observe plant-mediated interactions between aphid species in its presence and absence. At 23 degrees C, sugarcane aphid nymphs matured 1.5 d faster than greenbug nymphs on susceptible hybrid P8500, but at similar rates on the resistant line, which delayed maturity by 1-1.5 d in both species and increased juvenile mortality by three- to fourfold. Sugarcane aphid reproductive rate was double that of greenbug on susceptible sorghum (4.45 vs. 2.30 nymphs per female per day), but not significantly different on the resistant one (3.09 vs. 2.27). Thus, PI 550610 expresses antibiosis, not tolerance, to these aphids. Coinfestation of P8500 had a positive effect on greenbug intrinsic rate of increase (rm), which changed to negative on KS 116B, whereas the rm of sugarcane aphid was unaffected by coinfestation with greenbug on either cultivar. The results indicate that KS 116B will be useful for producing sugarcane aphid-resistant hybrids, and that PI 550610 antibiosis changes the sugarcane aphid-greenbug interspecific relationship from commensalism to amensalism. PMID- 26357842 TI - Effect of treatment with a JAK2-selective inhibitor, fedratinib, on bone marrow fibrosis in patients with myelofibrosis. AB - BACKGROUND: Progressive bone marrow fibrosis (BMF) is a cardinal feature of many myeloproliferative neoplasms (MPNs) and there is a documented association between the severity of BMF and overall prognosis. We conducted an exploratory analysis of sequential BMF data from two phase I studies of long-term treatment with the Janus kinase 2 (JAK2) inhibitor fedratinib in patients with myelofibrosis. METHODS: Bone marrow samples were obtained at baseline and after every six cycles (24 weeks) of daily fedratinib treatment. Fibrosis was centrally assessed by three independent haematopathologists, who were blinded to the patients' data, and graded according to European Consensus Myelofibrosis Grading Criteria. The analysis population comprised patients with a baseline BMF grade >=1, and at least one post-baseline BMF grade assessment. Changes in BMF grade compared with baseline were classified as improvement (>=1 grade reduction), stabilisation (no change in any baseline BMF grade <3) or worsening (>=1 grade increase). RESULTS: Twenty-one patients were included in the analysis. A total of 153 bone marrow samples were analysed. Improvement or stabilisation of BMF from baseline was recorded in 15 of 18 (83%) evaluable patients at cycle 6 and in four of nine (44%) evaluable patients at cycle 30. Two patients achieved resolution of their BMF (grade = 0) by cycle 12. CONCLUSIONS: This exploratory analysis indicates that improvement or even resolution of BMF may be achievable with JAK2 inhibitor therapy in some patients with MPNs and myelofibrosis. PMID- 26357845 TI - Larvicidal Effects of Four Citrus Peel Essential Oils Against the Arbovirus Vector Aedes albopictus (Diptera: Culicidae). AB - In this study, we evaluated the larvicidal activity of four citrus essential oils (EOs; sweet orange, mandarin, bergamot, and lemon) against the arbovirus vector Aedes albopictus (Skuse) (Diptera: Culicidae) under laboratory conditions. Through gas chromatography-mass spectrometry (GC-MS) analyses, we found that in sweet orange, mandarin, and lemon EOs, limonene was the most abundant compound, whereas linalyl acetate was the most abundant in the bergamot EO. All tested EOs showed a marked larvicidal activity, in particular sweet orange, lemon, and bergamot that killed all treated larvae. After 24 h of exposure, the LC50 values of the tested citrus EOs ranged from 145.27 (lemon EO) to 318.07 mg liter(-1) (mandarin EO), while LC(95) ranged from 295.13 to 832.44 mg liter(-1). After 48 h of exposure, the estimated LC(50) values decreased to values ranging from 117.29 to 209.38 mg liter(-1), while LC(95) ranged from 231.85 to 537.36 mg liter(-1). The results obtained from these evaluations, together with the large availability at reasonable costs of citrus EOs, are promising for the potential development of a new botanical mosquitocide. PMID- 26357846 TI - Survival of Corn Earworm (Lepidoptera: Noctuidae) on Bt Maize and Cross Pollinated Refuge Ears From Seed Blends. AB - Refuge is mandated in the United States where genetically modified maize (Zea mays L.) expressing insecticidal proteins derived from Bacillus thuringiensis Berliner (Bt) are cultivated. Currently, refuge is deployed in different ways including blocks, field strips, or seed blends containing Bt and non-Bt maize. Seed blends provide practical advantages for refuge implementation. However, concerns related to the movement of insect larvae, potential differential survival of heterozygous resistant larvae, reduction in insect production, and cross-pollination of ears resulting in sublethal selection, have delayed seed blend use for Lepidoptera in the southern United States, where maize plantings are used as refuge for Helicoverpa zea (Boddie). In this study, we evaluated the relative survival of H. zea in Bt events and in seed blends compared with pure stand refuge and the relative survival of H. zea on the individual components of the pyramid 1507xMON810xMIR162. The results showed variation on the production of H. zea in refuge plants from seed blends compared with pure stand refuge plants. The relative survival of H. zea on the events 1507, MON810, MIR162, and 1507xMON810xMIR162 ranked similarly across the three locations tested. These results can be used in computer simulation modeling efforts to evaluate the feasibility of seed blends as a refuge deployment strategy with the pyramid 1507xMON810xMIR162. Because the reduction on survival of H. zea due to blending was variable, a sensitivity analysis that includes all possible scenarios of reduction in survival should be considered. PMID- 26357847 TI - Quality of prenatal care questionnaire: psychometric testing in an Australia population. AB - BACKGROUND: The quality of antenatal care is recognized as critical to the effectiveness of care in optimizing maternal and child health outcomes. However, research has been hindered by the lack of a theoretically-grounded and psychometrically sound instrument to assess the quality of antenatal care. In response to this need, the 46-item Quality of Prenatal Care Questionnaire (QPCQ) was developed and tested in a Canadian context. The objective of this study was to validate the QPCQ and to establish its internal consistency reliability in an Australian population. METHODS: Study participants were recruited from two public maternity services in two Australian states: Monash Health, Victoria and Wollongong Hospital, New South Wales. Women were eligible to participate if they had given birth to a single live infant, were 18 years or older, had at least three antenatal visits during the pregnancy, and could speak, read and write English. Study questionnaires were completed in hospital. A confirmatory factor analysis (CFA) was conducted. Construct validity, including convergent validity, was further assessed against existing questionnaires: the Patient Expectations and Satisfaction with Prenatal Care (PESPC) and the Prenatal Interpersonal Processes of Care (PIPC). Internal consistency reliability of the QPCQ and each of its six subscales was assessed using Cronbach's alpha. RESULTS: Two hundred and ninety-nine women participated in the study. CFA verified and confirmed the six factors (subscales) of the QPCQ. A hypothesis-testing approach and an assessment of convergent validity further supported construct validity of the instrument. The QPCQ had acceptable internal consistency reliability (Cronbach's alpha = 0.97), as did each of the six factors (Cronbach's alpha = 0.74 to 0.95). CONCLUSIONS: The QPCQ is a valid and reliable self-report measure of antenatal care quality. This instrument fills a scientific gap and can be used in research to examine relationships between the quality of antenatal care and outcomes of interest, and to examine variations in antenatal care quality. It also will be useful in quality assurance and improvement initiatives. PMID- 26357848 TI - Three-dimensional X-ray microcomputed tomography of carbonates and biofilm on operated cathode in single chamber microbial fuel cell. AB - Power output limitation is one of the main concerns that need to be addressed for full-scale applications of the microbial fuel cell technology. Fouling and biofilm growth on the cathode of single chamber microbial fuel cells (SCMFC) affects their performance in long-term operation with wastewater. In this study, the authors report the power output and cathode polarization curves of a membraneless SCMFC, fed with raw primary wastewater and sodium acetate for over 6 months. At the end of the experiment, the whole cathode surface is analyzed through X-ray microcomputed tomography (microCT), scanning electron microscopy, and energy-dispersive X-ray spectroscopy (EDX) to characterize the fouling layer and the biofilm. EDX shows the distribution of Ca, Na, K, P, S, and other elements on the two faces of the cathode. Na-carbonates and Ca-carbonates are predominant on the air (outer) side and the water (inner) side, respectively. The three-dimensional reconstruction by X-ray microCT shows biofilm spots unevenly distributed above the Ca-carbonate layer on the inner (water) side of the cathode. These results indicate that carbonates layer, rather than biofilm, might lower the oxygen reduction reaction rate at the cathode during long-term SCMFC operation. PMID- 26357849 TI - The tumor area occupied by Tbet+ cells in deeply invading cervical cancer predicts clinical outcome. AB - BACKGROUND: Deep invasion of the normal surrounding tissue by primary cervical cancers is a prognostic parameter for postoperative radiotherapy and relatively worse survival. However, patients with tumor-specific immunity in the blood at the time of surgery displayed a much better disease free survival. Here we analyzed if this was due to a more tumor-rejecting immune population in the tumor. METHODS: Tumor sections from a group of 58 patients with deep normal tissue-invading cervical tumors were stained for the presence of immune cells (CD45), IFNgamma-producing cells (Tbet) and regulatory T cells (Foxp3) by immunohistochemistry. The slides were scanned and both the tumor area and the infiltration of the differently stained immune cells were objectively quantified using computer software. RESULTS: We found that an increased percentage of tumor occupied by CD45+ cells was strongly associated with an enhanced tumor infiltration by Tbet+ cells and Foxp3+ cells. Furthermore, the area occupied by CD45+ immune cells, Tbet+ cells but not Foxp3+ cells within the tumor were, in addition to the lymph node status of patients, associated with a longer disease free survival and disease specific survival. Moreover, interaction analyses between these immune parameters and lymph node status indicated an independent prognostic effect of tumor infiltrating Tbet+ cells. This was confirmed in a multivariate Cox analysis. CONCLUSIONS: The area occupied by a preferentially type I oriented CD45+ cell infiltrate forms an independent prognostic factor for recurrence-free and disease-specific survival on top of the patient's lymph node status. PMID- 26357850 TI - Are Th17 cells and their cytokines a therapeutic target in Guillain-Barre syndrome? AB - INTRODUCTION: Guillain-Barre syndrome (GBS) is an immune-mediated inflammatory disorder of the peripheral nervous system (PNS). Experimental autoimmune neuritis (EAN) is a useful animal model for studying GBS. Currently, GBS remains a life threatening disorder and more effective therapeutic strategies are in urgent need. AREAS COVERED: Accumulating evidence has revealed that T helper (Th) 17 cells and their cytokines are pathogenic in GBS/EAN. Drugs attenuated clinical signs of GBS/EAN, in part, by decreasing Th17 cells or IL-17A. Th17 cells and their cytokines might be potential therapeutic targets. Approaches targeting Th17 cells or their cytokines are in development in treating Th17 cells-involved disorders. In this review, we summarize the up-to-date knowledge on roles of Th17 cells and their cytokines in GBS/EAN, as well potential approaches targeting Th17 cells and their cytokines as clinical applications. EXPERT OPINION: As Th17 cells produce different sets of pro-inflammatory cytokines and Th17-related cytokines are not exclusively produced by Th17 cells, targeting Th17 cell development may be superior to blocking a single Th17 cytokine to treat Th17 cells-involved disorders. Considering the essential role of retinoic acid-related orphan receptor gammaT (RORgammaT) and IL-23 in Th17 cell development, RORgammaT inhibitors or IL-23 antagonists may provide better clinical efficacy in treating GBS/EAN. PMID- 26357851 TI - Light signaling induces anthocyanin biosynthesis via AN3 mediated COP1 expression. AB - Light signaling plays a pivotal role in controlling plant morphogenesis, metabolism, growth and development. The central process of light signaling pathway is to build the link between light signals and the expression of genes involved. Although studies focused on light signaling toward metabolism have been documented well in the past several decades, most regulation networks of light signaling in a specific metabolic production largely remained unknown. Anthocyanin accumulation in plant tissues depends on the availability of light signals, but only little is known about the potential regulation network underlying light signal controls anthocyanin biosynthesis. Here, we briefly review the recent progress on the light-triggered anthocyanin biosynthesis via ANGUSTIFOLIA3 (AN3) and CONSTITUTIVE PHOTOMORPHOGENIC1 (COP1) network in Arabidopsis. PMID- 26357852 TI - Effects of cytochalasin congeners, microtubule-directed agents, and doxorubicin alone or in combination against human ovarian carcinoma cell lines in vitro. AB - BACKGROUND: Although the actin cytoskeleton is vital for carcinogenesis and subsequent pathology, no microfilament-directed agent has been approved for cancer chemotherapy. One of the most studied classes of microfilament-directed agents has been the cytochalasins, mycotoxins known to disrupt the formation of actin polymers. In the present study, we sought to determine the effects of cytochalasin congeners toward human drug sensitive and multidrug resistant cell lines. METHODS: SKOV3 human ovarian carcinoma and several multidrug resistant derivatives were tested for sensitivity against a panel of nine cytochalasin congeners, as well as three clinically approved chemotherapeutic agents (doxorubicin, paclitaxel, and vinblastine). In addition, verapamil, a calcium ion channel blocker known to reverse P-glycoprotein (P-gp) mediated drug resistance, was used in combination with multiple cytochalasin congeners to determine whether drug sensitivity could be increased. RESULTS: While multidrug resistant SKVLB1 had increased drug tolerance (was more resistant) to most cytochalasin congeners in comparison to drug sensitive SKOV3, the level of resistance was 10 to 1000 fold less for the cytochalasins than for any of the clinically approved agents. While cytochalasins did not appear to alter the expression of ATP binding cassette (ABC) transporters, several cytochalasins appeared to inhibit the activity of ABC transporter-mediated efflux of rhodamine 123 (Rh123), suggesting that these congeners do have affinity for drug efflux pumps. Cytochalasins also appeared to significantly decrease the F/G-actin ratio in both drug sensitive and drug resistant cells, indicative of marked microfilament inhibition. The cytotoxicity of most cytochalasin congeners could be increased with the addition of verapamil, and the drug sensitivity of resistant SKVLB1 to the clinically approved antineoplastic agents could be increased with the addition of cytochalasins. As assessed by isobolographic analysis and Chou-Talalay statistics, cytochalasin B and 21,22-dihydrocytochalasin B (DiHCB) demonstrated notable synergy with doxorubicin and paclitaxel, warranting further investigation in a tumor-bearing mammalian model. CONCLUSION: Cytochalasins appear to inhibit the activity of P-gp and potentially other ABC transporters, and may have novel activity against multidrug resistant neoplastic cells that overexpress drug efflux proteins. PMID- 26357853 TI - Optimal cutoff value of basal anti-mullerian hormone in iranian infertile women for prediction of ovarian hyper-stimulation syndrome and poor response to stimulation. AB - AIM: We intended to establish the threshold of Anti-Mullerian Hormone (AMH) for detection of Ovarian Hyper-Stimulation Syndrome (OHSS) and poor response to treatment in Iranian infertile women. METHODS: Pre-stimulation menstrual cycle day-3 hormonal indices including basal AMH values were measured in 105 infertile women aged 32.5 +/- 4.3 years. Patients underwent long GnRH agonist Controlled Ovarian Hyperstimulation (COH) in a referral infertility center (Tehran, Iran). The gonadotropin dose was determined based on the age and basal serum Follicular Stimulating Hormone (FSH) level. The IVF/ICSI cycles were followed and the clinical and sonographic data were recorded. RESULTS: Sixteen cases developed OHSS. The prevalence of PCOS was higher in subjects with OHSS [62.5 % (38.8-86.2) vs. 17 % (9.2-24.9)]. The patients with OHSS had higher ovarian follicular count [23.7 (3.2) vs. 9.1 (0.5); p < 0.05], collected oocytes [13.5 (1.9) vs. 6.9 (0.5); p < 0.05] and AMH level [7.9 (0.7) vs. 3.6 (0.3); p < 0.05]. Basal AMH level and oocyte yields (but not age, BMI, and PCOS) correlated with occurrence of OHSS; and only the AMH levels were associated with poor ovarian response (oocytes yield <= 4). The optimal cutoff value for the prediction of OHSS was 6.95 ng/ml (area under the receiver operating characteristics curve: 0.86; CI: 0.78-0.95; sensitivity: 75 %; specificity: 84 %; odds ratio for occurrence of OHSS: 9 and p < 0.001). The optimal cut point to discriminate poor response (oocytes <=4) was 1.65 ng/ml ( AUC : 0.8; CI: 0.69-0.91; sensitivity: 89 % specificity : 71 %; and OR = 23.8 and P value <0.001). CONCLUSIONS: Iranian women with basal AMH level > 6.95 ng/ml are at high risk of developing OHSS and those with AMH level < 1.65 ng/ml are poor responders. PMID- 26357854 TI - The potential of Beclin 1 as a therapeutic target for the treatment of breast cancer. AB - INTRODUCTION: Beclin 1 plays a crucial role in autophagy via the Beclin 1 interactome, and is involved in various biological processes such as protein sorting, chemokinesis, and cell death. Via these biologic functions, Beclin 1 contributes to both tumor suppression and tumor progression. AREAS COVERED: Beclin 1 plays a key biologic function on cell homeostasis and affects tumorigenesis. In this review, detailing up-to-date knowledge on the tumorigenic role of Beclin 1, its implication in breast cancer, and its utility as a breast cancer-specific drug target is discussed. EXPERT OPINION: Because Beclin 1 is expressed in breast cancer cells, Beclin 1 could be a unique, effective drug target for the prevention and treatment of breast cancer. However, the expression of Beclin 1 varies according to cancer molecular subtypes, and Beclin 1 is involved in both breast cancer suppression and tumor progression; therefore, the decision of using a Beclin 1 inducer or inhibitor should be made based on breast cancer stage and subtype. PMID- 26357855 TI - RNAi-mediated gene silencing of WsSGTL1 in W.somnifera affects growth and glycosylation pattern. AB - Sterol glycosyltransferases (SGTs) belong to family 1 of glycosyltransferases (GTs) and are enzymes responsible for synthesis of sterol-glucosides (SGs) in many organisms. WsSGTL1 is a SGT of Withania somnifera that has been found associated with plasma membranes. However its biological function in W.somnifera is largely unknown. In the present study, we have demonstrated through RNAi silencing of WsSGTL1 gene that it performs glycosylation of withanolides and sterols resulting in glycowithanolides and glycosylated sterols respectively, and affects the growth and development of transgenic W.somnifera. For this, RNAi construct (pFGC1008-WsSGTL1) was made and genetic transformation was done by Agrobacterium tumefaciens. HPLC analysis depicts the reduction of withanoside V (the glycowithanolide of W.somnifera) and a large increase of withanolides (majorly withaferin A) content. Also, a significant decrease in level of glycosylated sterols has been observed. Hence, the obtained data provides an insight into the biological function of WsSGTL1 gene in W.somnifera. PMID- 26357856 TI - [A short history of infectious diseases since the fifties of the last century and the importance of vaccination]. AB - Vaccination in the Czech lands has a long history; it begun during the Austro Hungarian Empire in 1803 by vaccination against smallpox, and in the late 19th century by vaccination against rabies. In the second half of the 20th century, the basic vaccination included also other vaccines. Thanks to paediatricians, vaccination coverage of children was so high that in addition to the immunity of individuals the collective immunity was also significant. The incidence of infectious diseases has dropped significantly. Today the population, both medical and lay, almost does not know the classic childrens infectious diseases or their risk of complications. This creates a feeling in recent years that vaccination is unnecessary and that it is a source of complication and, therefore, better not to vaccinate. However, diseases, except for smallpox, have not disappeared, and for the susceptible unvaccinated individuals they represent a great risk. There are now occurring at atypical age groups where their diagnosis is even not considered. Therefore, it is important to return to the course of disease as well as to the potentially serious complications in unvaccinated people. PMID- 26357857 TI - [New options for therapeutic revascularization in lower extremity limb ischemia linked to the diabetic foot syndrome by autologous stem cell transplantation]. AB - Type 2 diabetes incidence is growing worldwide. It is in up to 50% cases linked with diabetic foot syndrome. This is associated with peripheral neuropathy and peripheral artery disease which increases risk of defects with impaired healing. Resulting high number of amputations has major influence on the quality of life and constitutes serious clinical issue. In recent years numerous clinical studies have shown positive effect of new treatment modality using regenerative potential of the autologous stem cells transplantation. This review tries to summarize existing results of therapeutic revascularization using stem cell and to outline mechanism of their action. PMID- 26357858 TI - [IgA Nephropathy. Facts, uncertainties, and potential causal therapy approaches]. AB - IgA nephropathy is currently the most frequently investigated glomerulonephritis. The disease is defined by the presence of dominant or co-dominant deposits of IgA1 in the glomerular mesangium. Circulating immune complexes are most likely the source of the deposited IgA1. However, it is also possible that the aggregates of structurally altered IgA1 or enhanced binding to IgA receptors expressed on mesangial cells lead to deposition. The cause of the formation of immune complexes responsible for IgA nephropathy lies in the incomplete O-linked oligosaccharide side chains, which, due to the deficiency of corresponding glycosyltransferases, lack terminal galactose residues leading to the exposure of N-acetylgalactosamine. Naturally occurring antibodies of the IgG or IgA1 isotype bind to this sugar antigen. In the clinical course, we differentiate between the early stage usually characterized by hematuria, and a variable late stage characterized either by a clinical remission, by persistence of hematuria, or by increasing proteinuria and blood pressure and decreasing renal function in one third of the patients. In the early stage, it is difficult to predict the prognosis of IgA nephropathy, either on the basis of clinical presentation and morphological findings, or according to the level of galactose-deficient IgA1 in the circulation. The reliable criteria of serious prognosis emerge only in the later stages of the disease and include proteinuria, hypertension, and histologically apparent tubular atrophy and interstitial sclerosis. The dominant trend in the treatment of IgA nephropathy is the emphasis on administration of ACE inhibitors/sartans, which are introduced into the treatment at the time of microalbuminuria. If proteinuria does not decrease below 1 g/24 h, treatment with prednisone is justifiable. New findings concerning the molecular/cellular mechanism involved in the pathogenesis of IgA nephropathy suggest the possible therapeutical interference with the generation of nephritogenic immune complexes by a selective blocking of the IgA1 molecules with altered glycan structures using monovalent reagents. PMID- 26357859 TI - [Gastric lavage after peroral intoxication--controversial views]. AB - Gastric lavage after ingestion of excessive amounts of a drug/poison--yes or no? If yes, at what time intervals from ingestion? On one side stand some authors who emphasize the complications, contraindications, and low yield of this procedure. These authors recommended that gastric lavage should be performed only within 30 60 minutes after ingestion of toxic doses of a drug/poison. Later lavage usually has no clinical benefit. On the other side stand some other authors who recommend gastric lavage in patients as late as 6 hours after intoxication. In some cases, when the ingested substance slows gastric emptying, they even recommend lavage until 24 hours after intoxication. Based on our experience, it is necessary to support strongly the second group of the authors and recommend the extension of the time interval when to perform gastric lavage in intoxication. PMID- 26357860 TI - [Health effects of ambient ultrafine particles--the project UFIREG]. AB - BACKGROUND: The project "Ultrafine particles--an evidence based contribution to the development of regional and European environmental and health policy" (UFIREG) started in July 2011 and ended in December 2014. It was implemented through the Central Europe Programme and co-financed by the European Regional Development Fund. Five cities in four Central European countries participated in the study: Augsburg (Germany), Chernivtsi (Ukraine), Dresden (Germany), Ljubljana (Slovenia) and Prague (Czech Republic). The aim of the UFIREG project was to improve the knowledge base on possible health effects of ambient ultrafine particles (UFP) and to raise overall awareness of environmental and health care authorities and the population. METHODS: Epidemiological studies in the frame of the UFIREG project have assessed the short-term effects of UFP on human mortality and morbidity, especially in relation to cardiovascular and respiratory diseases. Official statistics were used to determine the association between air pollution concentration and daily (cause-specific: respiratory and cardiovascular) hospital admissions and mortality. Associations of UFP levels and health effects were analysed for each city by use of Poisson regression models adjusting for a number of confounding factors. RESULTS: Results on morbidity and mortality effects of UFP were heterogeneous across the five European cities investigated. Overall, an increase in respiratory hospital admissions and mortality could be detected for increases in UFP concentrations. Results on cardiovascular health were less conclusive. CONCLUSION: Further multi-centre studies such as UFIREG are needed preferably investigating several years in order to produce powerful results. PMID- 26357861 TI - [Analysis of serum levels of Dickkopf-1 (DKK-1) in monoclonal gammopathy of undetermined significance and multiple myeloma]. AB - BACKGROUND: Several recent studies aim at the detection of biological parameters that enable more precise diagnostics and stratification of monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM). The objective of our study was to assess the potential contribution of serum levels of Dickkopf-1 (DKK-1) in MGUS and MM from the point of more specific differentiation of both conditions, and the relationship of DKK-1 to selected laboratory parameters, individual forms and clinical stages of both conditions. METHODS AND RESULTS: The analyzed cohort consisted of 46 individuals with MGUS and 152 patients with MM at the time of diagnosis. For the assessment of serum levels of DKK-1 we used ELISA method. We assessed also serum levels of free light chains (FLC) kappa and lambda using the Freelite system, and beta2-microglobulin (beta2-M) using the Immulite 1000 method. For statistical estimation we used: Pearson chi2-test, U-test according to Mann-Whitney and Kruskal-Wallis test. Our analysis revealed that there was no significant difference between the levels of DKK-1 in MGUS risk groups (0-3) and between the states with different FLC concentration including the kappa/lambda index of monoclonality. In MM there was a significant relationship of DKK-1 to the level of hemoglobin (p<0.008) but not to the levels of FLC, creatinine or beta2-microglobulin. Within the Durie-Salmon staging system, there were significant differences of DKK-1 between the stages I vs. III (p=0.001) and I vs. II+III (p=0.002). In the International Staging System (ISS) there were significant differences only between stages 1 vs. 2+3 (p=0.045). Although there was no overall significant difference of DKK-1 levels between MGUS and MM, there was a difference between MGUS vs stage III (p=0.001) and II+III (p=0.001) according to Durie-Salmon, and also MGUS vs. stage 2 (p=0.005) and vs. stages 2+3 (p=0,012) according to ISS. There were no significant differences in DKK-1 between MGUS and initial/asymptomatic form of MM (stage I). CONCLUSION: Although there was a significant difference of serum levels of DKK-1 between MGUS and initial/asymptomatic stage of MM when compared to advanced stage MM, and in patients with different Hb levels, we do not find the evaluation of serum levels of DKK-1 useful for routine discrimination of MGUS and MM, and for the specification of temporary stratification systems. PMID- 26357862 TI - [The story of Appendix]. AB - Acute appendicitis is the most frequent acute abdominal emergency. Appendicitis may have been recorded by Aretaeus the Cappadocean in 30 AD. A description of the appendix was provided by the anatomist Berengario de Carpi in 1521. The first appendicectomy was performed by Claudius Amyand in 1735. Turning point in the story of appendix was public lecture of pathologist-physician Reginald Fitz in 1886. Fitz used the term "appendicitis". The area of maximal tenderness with appendicitis was immortalised by Charles McBurney. In the story of appendicitis many names figure, for example Niels Thorkild Rovsing, Jacob Moritz Blumberg, Otto Lanz, Frederic Treves and other. Kurt Semm introduced laparoscopic appendicectomy in 1988. PMID- 26357863 TI - [Gout and its manifestations, description and treatment in ancient times]. AB - Gout is a very old disease, which exists for thousands of years. The first descriptions interpreted as the symptoms of gout can be found already in the Egyptian medical papyri dating to the 3rd mill. BC. In the Ancient world, many physicians dealt with the causes, diagnostics and the treatments of gout, such as Hippocrates of Cos, Diocles of Carystus or Claudios Galenos. A personified gout (as the goddess Podagra) is also to be found in the Ancient mythology and culture. Several human remnants of the people suffering from gout are preserved from the Antiquity as well. PMID- 26357865 TI - A simple method for the addition of rotenone in Arabidopsis thaliana leaves. AB - A simple and reproducible method for the treatment of Arabidopsis thaliana leaves with rotenone is presented. Rosette leaves were incubated with rotenone and Triton X-100 for at least 15 h. Treated leaves showed increased expression of COX19 and BCS1a, 2 genes known to be induced in Arabidopsis cell cultures after rotenone treatment. Moreover, rotenone/Triton X-100 incubated leaves presented an inhibition of oxygen uptake. The simplicity of the procedure shows this methodology is useful for studying the effect of the addition of rotenone to a photosynthetic tissue in situ. PMID- 26357864 TI - Effects of low-dose clonidine on cardiovascular and autonomic variables in adolescents with chronic fatigue: a randomized controlled trial. AB - BACKGROUND: Chronic Fatigue Syndrome (CFS) is a common and disabling condition in adolescence with few treatment options. A central feature of CFS is orthostatic intolerance and abnormal autonomic cardiovascular control characterized by sympathetic predominance. We hypothesized that symptoms as well as the underlying pathophysiology might improve by treatment with the alpha2A-adrenoceptor agonist clonidine. METHODS: A total of 176 adolescent CFS patients (12-18 years) were assessed for eligibility at a single referral center recruiting nation-wide. Patients were randomized 1:1 by a computer system and started treatment with clonidine capsules (25 MUg or 50 MUg twice daily, respectively, for body weight below/above 35 kg) or placebo capsules for 9 weeks. Double-blinding was provided. Data were collected from March 2010 until October 2012 as part of The Norwegian Study of Chronic Fatigue Syndrome in Adolescents: Pathophysiology and Intervention Trial (NorCAPITAL). Effect of clonidine intervention was assessed by general linear models in intention-to-treat analyses, including baseline values as covariates in the model. RESULTS: A total of 120 patients (clonidine group n = 60, placebo group n = 60) were enrolled and started treatment. There were 14 drop outs (5 in the clonidine group, 9 in the placebo group) during the intervention period. At 8 weeks, the clonidine group had lower plasma norepinephrine (difference = 205 pmol/L, p = 0.05) and urine norepinephrine/creatinine ratio (difference = 3.9 nmol/mmol, p = 0.002). During supine rest, the clonidine group had higher heart rate variability in the low-frequency range (LF-HRV, absolute units) (ratio = 1.4, p = 0.007) as well as higher standard deviation of all RR intervals (SDNN) (difference = 12.0 ms, p = 0.05); during 20 degrees head-up tilt there were no statistical differences in any cardiovascular variable. Symptoms of orthostatic intolerance did not change during the intervention period. CONCLUSIONS: Low-dose clonidine reduces catecholamine levels in adolescent CFS, but the effects on autonomic cardiovascular control are sparse. Clonidine does not improve symptoms of orthostatic intolerance. TRIAL REGISTRATION: Clinical Trials ID: NCT01040429, date of registration 12/28/2009. PMID- 26357866 TI - Potential effects of vildagliptin on biomarkers associated with prothrombosis in diabetes mellitus. AB - OBJECTIVE: Diabetes mellitus (DM) is one of the risks linked with susceptibility of thrombosis. We tried to inspect the effect of a novel oral antidiabetic agent, vildagliptin, in preventing prothrombosis associated with DM. RESEARCH DESIGN AND METHODS: DM was produced by a dose of streptozotocin (STZ) or in albino wistar rats. Rats were treated orally with pioglitazone, standard treatment and vildagliptin alone and in combination for 3 weeks. Finally, the varied levels of coagulation biomarkers, including activated partial thromboplastin time (aPTT), prothrombin time (PT) and fibrinogen and inflammatory parameters, nitric oxide (NO), C-reactive protein (CRP) and TNF-alpha and lipid profile were estimated along with platelet count and total leukocyte count (TLC). In vitro fibrinolytic activity of both the drugs was also determined. RESULTS: Vildagliptin significantly reduced cholesterol, triglycerides, TLC, CRP and TNF-alpha and increased aPTT and NO levels in STZ diabetic rats. However, pioglitazone was more successful in reducing fibrinogen and platelet count. Nevertheless, combination of the drugs was also effective than pioglitazone or vildagliptin alone in improvising hypercoagulation and inflammatory biomarkers. CONCLUSION: It is evident from the present study that vildagliptin has an influence on the biomarkers linked to the progression of thrombosis and may delay thrombogenesis linked to DM. Hence, vildagliptin alone and in combination might prove as an encouraging therapy for DM-linked thrombosis marked by inflammation and hypercoagulation. PMID- 26357868 TI - Emil Kraepelin: Icon and Reality. AB - In the last third of the 20th century, the German psychiatrist Emil Kraepelin (1856-1926) became an icon of postpsychoanalytic medical-model psychiatry in the United States. His name became synonymous with a proto-biological, antipsychological, brain-based, and hard-nosed nosologic approach to psychiatry. This article argues that this contemporary image of Kraepelin fails to appreciate the historical contexts in which he worked and misrepresents his own understanding of his clinical practice and research. A careful rereading and contextualization of his inaugural lecture on becoming chair of psychiatry at the University of Tartu (known at the time as the University of Dorpat) in 1886 and of the numerous editions of his famous textbook reveals that Kraepelin was, compared with our current view of him, 1) far more psychologically inclined and stimulated by the exciting early developments of scientific psychology, 2) considerably less brain-centric, and 3) nosologically more skeptical and less doctrinaire. Instead of a quest for a single "true" diagnostic system, his nosological agenda was expressly pragmatic and tentative: he sought to sharpen boundaries for didactic reasons and to develop diagnoses that served critical clinical needs, such as the prediction of illness course. The historical Kraepelin, who struggled with how to interrelate brain and mind-based approaches to psychiatric illness, and who appreciated the strengths and limitations of his clinically based nosology, still has quite a bit to teach modern psychiatry and can be a more generative forefather than the icon created by the neo Kraepelinians. PMID- 26357867 TI - Characterization of Puerto Rican West Nile Virus isolates in mice. AB - BACKGROUND: West Nile virus (WNV) is a neurotropic arbovirus that was first isolated in 1937 in the West Nile District of Uganda. The virus emerged in New York in 1999 and is now endemic in North America (2007). The first virus isolates from Puerto Rico were obtained in 2007 from a chicken (PR20wh) and a mosquito pool (PR423). Our study further characterized these viral isolates using in vitro plaque morphology assays and in vivo using a Balb/c mice pathogenesis model. METHODS AND RESULTS: In the in vitro experiments, PR WNV isolates produced significantly smaller plaques in Vero cells compared to the New York 1999 strain (NY99). For the in vivo experiments, PR WNV isolates were propagated in mammalian (Vero) and insect (C6/36) cell lines and then inoculated in Balb/c mice. When WNV was propagated in Vero cells, we observed a trend towards significance in the survival rate with PR20wh compared to NY99 (log rank, p = 0.092). Regardless of whether the viral isolates were propagated in Vero or C6/36 cells, we found a significantly greater survival in mice infected with PR20wh strain, when compared to NY99 (log rank, p = 0.04), while no statistical difference was detected between PR423 and NY99 (p = 0.84). The average survival time (AST) in mice was significantly lower in C6/36-derived PR423 when compared to C6/36-derived NY99 (t test, p = 0.013), and Vero-derived PR423 (t-test, p < 0.001). Eight days post infection in mice the viral load in brain tissue for Vero-derived PR423 was significantly higher when compared to NY99 and PR20wh. CONCLUSIONS: These results suggest that the PR WNV isolate, PR20wh, is a less pathogenic strain in mice than NY99. Moreover, we found that PR423 is a pathogenic isolate that causes faster mortality than NY99, when propagated in C6/36. PMID- 26357869 TI - Conservation of the Ustilago maydis effector See1 in related smuts. AB - Ustilago maydis is a biotrophic fungus that induces formation of tumors in maize (Zea mays L). In a recent study we identified See1 (Seedling efficient effector 1) as an U. maydis organ-specific effector required for tumor formation in leaves. See1 is required for U. maydis induced reactivation of plant DNA synthesis during leaf tumor progression. The protein is secreted from biotrophic hyphae and localizes to the cytoplasm and nucleus of plant cell. See1 interacts with maize SGT1, a cell cycle and immune regulator, interfering with its MAPK triggered phosphorylation. Here, we present new data on the conservation of See1 in other closely related smuts and experimental data on the functionality of See1 ortholog in Ustilago hordei, the causal agent of barley covered smut disease. PMID- 26357870 TI - A population-based case-control study on statin exposure and risk of acute diverticular disease. AB - OBJECTIVE: A reduced risk of perforated diverticular disease among individuals with current statin exposure has been reported. The aim of the present study was to investigate whether statins reduce the risk of acute diverticular disease. MATERIAL AND METHODS: A nation-wide population-based case-control study was performed, including 13,127 cases hospitalised during 2006-2010 with a first-time diagnosis of colonic diverticular disease, and 128,442 control subjects (matched for sex, age, county of residence and calendar year). Emergency surgery, assumed to be a proxy for complicated diverticulitis, was performed on 906 of the cases during the index admission, with 8818 matched controls. Statin exposure was classified as "current" or "former" if a statin prescription was last dispensed <= 125 days or >125 days before index date, respectively. The association between statin exposure and acute diverticular disease was investigated by conditional logistic regression, including models adjusting for country of birth, educational level, marital status, comorbidities, nonsteroidal anti-inflammatory drug/steroid exposure and healthcare utilisation. RESULTS: A total of 1959 cases (14.9%) and 16,456 controls (12.8%) were current statin users (crude OR 1.23 [95% CI 1.17 1.30]; fully adjusted OR 1.00 [0.94-1.06]). One hundred and thirty-two of the cases subjected to surgery (14.6%), and 1441 of the corresponding controls (16.3%) were current statin users (crude OR 0.89 [95% CI 0.73-1.08]; fully adjusted OR 0.70 [0.55-0.89]). CONCLUSIONS: The results do not indicate that statins affect the development of symptomatic diverticular disease in general. However, current statin use was associated with a reduced risk of emergency surgery for diverticular disease. PMID- 26357871 TI - Operative management of cryptorchidism: guidelines and reality--a 10-year observational analysis of 3587 cases. AB - BACKGROUND: Undescended testis (UDT) is the most common disorder in pediatric surgery and one of the most important risk factors for malignancy and subfertility. In 2009 local guidelines were modified and now recommend treatment to be completed by the age of 1. Aim of this study was to analyze age distribution at the time of orchidopexy, whether the procedure is performed according to guideline recommendations and to assess primary care pediatricians' attitude regarding their treatment approach. METHODS: We retrospectively analyzed 3587 patients with UDT regarding age at orchidopexy between 2003 and 2012 in 13 German hospitals. Furthermore, we conducted an anonymized nation-wide survey among primary care pediatricians regarding their attitude toward management of UDT. RESULTS: Before modification of the guideline 78% (n = 1245) of the boys with UDT were not operated according to guideline recommendations. After the modification that number rose to 95% (n = 1472). 42% of the orchidopexies were performed on patients aged 4 to 17 years. 46% of the primary care pediatricians were not aware of this discrepancy and 38% would only initiate operative management after the first year of life. In hospitals with pediatric surgery departments significantly more patients received orchidopexy in their first year of life (p < .001). CONCLUSION: The guideline for UDT in Germany has not yet been implemented sufficiently. Timing of orchidopexy must be optimized in order to improve long-term prognosis. Both primary care providers and parents should be educated regarding the advantages of early orchidopexy in UDT. Prospective studies are needed to elucidate the high rate of late orchidopexies. PMID- 26357872 TI - Defense Mechanisms of Pregnant Mothers Predict Attachment Security, Social Emotional Competence, and Behavior Problems in Their Toddlers. AB - OBJECTIVE: For at-risk (single parent, low income, low support) mothers, healthy adaptation and the ability to manage stress have clear implications for parenting and the social-emotional well-being of their young offspring. The purpose of this longitudinal study was to examine associations between defense mechanisms in pregnant women and their toddlers' attachment security, social-emotional, and behavioral adjustment. METHOD: Participants were 84 pregnant women during their last trimester of pregnancy, recruited from community agencies primarily serving low-income families. Women were followed prospectively from pregnancy through 2 years after birth and completed several multimethod assessments during that period. Observations of mother-child interactions were also coded after the postnatal visits. RESULTS: Multiple regression analyses revealed that mothers' defense mechanisms were significantly associated with several toddler outcomes. Mature, healthy defenses were significantly associated with greater toddler attachment security and social-emotional competence and fewer behavior problems, and less mature defenses (disavowal in particular) were associated with lower levels of attachment security and social-emotional competence. Associations remained significant, or were only slightly attenuated, after controlling for demographic variables and partner abuse during pregnancy. CONCLUSIONS: The study findings suggest that defensive functioning in parents preparing for and parenting toddlers influences the parent-child attachment relationship and social emotional adjustment in the earliest years of life. Possible mechanisms for these associations may include parental attunement and mentalization, as well as specific caregiving behavior toward the child. Defensive functioning during times of increased stress (such as the prenatal to postnatal period) may be especially important for understanding parental influences on the child. PMID- 26357873 TI - Inter-organ defense networking: Leaf whitefly sucking elicits plant immunity to crown gall disease caused by Agrobacterium tumefaciens. AB - Plants have elaborate defensive machinery to protect against numerous pathogens and insects. Plant hormones function as modulators of defensive mechanisms to maintain plant resistance to natural enemies. Our recent study suggests that salicylic acid (SA) is the primary phytohormone regulating plant responses to Agrobacterium tumefaciens infection. Tobacco (Nicotiana benthamiana Domin.) immune responses against Agrobacterium-mediated crown gall disease were activated by exposure to the sucking insect whitefly, which stimulated SA biosynthesis in aerial tissues; in turn, SA synthesized in aboveground tissues systemically modulated SA secretion in root tissues. Further investigation revealed that endogenous SA biosynthesis negatively modulated Agrobacterium-mediated plant genetic transformation. Our study provides novel evidence that activation of the SA-signaling pathway mediated by a sucking insect infestation has a pivotal role in subsequently attenuating Agrobacterium infection. These results demonstrate new insights into interspecies cross-talking among insects, plants, and soil bacteria. PMID- 26357874 TI - Impact of portal hemodynamics on Doppler ultrasonography for predicting decompensation and long-term outcomes in patients with cirrhosis. AB - OBJECTIVE: Significance of portal hemodynamics for non-invasive marker of cirrhosis remains unclear. The aim was to determine the value of portal hemodynamics on Doppler ultrasound for predicting decompensation and prognosis in cirrhosis. METHODS: This retrospective study comprised 236 cirrhotic patients (132 males, 104 females; age 63.7 +/- 11.3 years; 110 compensated, 126 decompensated). Clinical data, including Doppler findings, were analyzed with respect to decompensation and prognosis. The median follow-up period was 33.2 months (0.1-95.4). RESULTS: Fifty-three patients developed clinical decompensation, 13 patients received liver transplantation, and 71 died. Higher model for end-stage liver disease score (p < 0.001) at baseline was the significant factor for the presence of decompensation. Higher alanine transaminase (p = 0.020), lower albumin (p = 0.002) and lower mean velocity in the portal trunk (p = 0.038) were significant factors for developing decompensation (best cut-off value: Alanine transaminase > 31 IU/L, albumin < 3.6 g/dL, and portal trunk < 12.8 cm/s). The cumulative incidence of decompensation was higher in patients with portal trunk < 12.8 cm/s (22.5% at 1 year, 71.2% at 5 years) than those without (6.9% at 1 year, 35.4% at 5 years; p < 0.001). The significant prognostic factors were hepatocellular carcinoma (p = 0.036) and lower albumin (p = 0.008) for compensated patients, and reversed portal flow (p = 0.028), overt ascites (p < 0.001), and higher bilirubin (p < 0.001) for decompensated patients. CONCLUSION: Portal hemodynamics offer a non-invasive marker for decompensation and prognosis of cirrhosis, suggesting a future direction for practical management. PMID- 26357875 TI - Sleeve lobectomy by video-assisted thoracic surgery versus thoracotomy for non small cell lung cancer. AB - BACKGROUND: Both video-assisted thoracic surgery (VATS) and thoracotomy are used for sleeve lobectomy for patients with non-small cell lung cancer (NSCLC). This retrospective study aimed to assess the safety and efficacy of VATS sleeve lobectomy for NSCLC patients. METHODS: Between May 2009 and May 2013, 51 sleeve lobectomies (10 by VATS and 41 by thoracotomy) were performed for patients with NSCLC. Operative characteristics and postoperative course were compared between two groups. RESULTS: Patient demographics were similar between the two groups. Thoracotomy patients had larger tumors compared with VATS patients (p = 0.02). VATS patients had a longer operating time (p < 0.001) but a shorter length of postoperative hospital stay (p = 0.009). The two groups did not differ in pathologic stage, histologic results, blood loss, ICU stay, amount of chest drainage, duration of chest drainage, numbers and distributions of dissected lymph nodes and the occurrence of complications. There were no perioperative deaths in the VATS group, whereas there was one death (2.4 %) in the thoracotomy group. There were no conversions to thoracotomy in the VATS group. The overall median survival between the two groups was similar (3.2 years VATS versus 3.2 years thoracotomy, log-rank p = 0.58). CONCLUSIONS: VATS sleeve lobectomy for the treatment of NSCLC is technically feasible and safe and is associated with comparable complication rates and survival compared with thoracotomy approach, but it deserves further investigation in large series. PMID- 26357876 TI - Inflammation: depression fans the flames and feasts on the heat. AB - Depression and inflammation fuel one another. Inflammation plays a key role in depression's pathogenesis for a subset of depressed individuals; depression also primes larger cytokine responses to stressors and pathogens that do not appear to habituate. Accordingly, treatment decisions may be informed by attention to questions of how (pathways) and for whom (predispositions) these links exist, which are the focus of this article. When combined with predisposing factors (moderators such as childhood adversity and obesity), stressors and pathogens can lead to exaggerated or prolonged inflammatory responses. The resulting sickness behaviors (e.g., pain, disturbed sleep), depressive symptoms, and negative health behaviors (e.g., poor diet, a sedentary lifestyle) may act as mediating pathways that lead to further, unrestrained inflammation and depression. Depression, childhood adversity, stressors, and diet can all influence the gut microbiome and promote intestinal permeability, another pathway to enhanced inflammatory responses. Larger, more frequent, or more prolonged inflammatory responses could have negative mental and physical health consequences. In clinical practice, inflammation provides a guide to potential targets for symptom management by signaling responsiveness to certain therapeutic strategies. For example, a theme across research with cytokine antagonists, omega-3 fatty acids, celecoxib, and exercise is that anti-inflammatory interventions have a substantially greater impact on mood in individuals with heightened inflammation. Thus, when inflammation and depression co-occur, treating them in tandem may enhance recovery and reduce the risk of recurrence. The bidirectional links between depression, inflammation, and disease suggest that effective depression treatments could have a far-reaching impact on mood, inflammation, and health. PMID- 26357877 TI - Species-specific cell mobility of bacteria-feeding myxamoebae in plasmodial slime molds. AB - On decaying wood or litter in forests, plasmodial slime molds (myxomycetes) represent a large fraction of eukaryotic protists that feed on bacteria. In his seminal book Experimental Physiology of Plants (1865), Julius Sachs referred to the multinucleate plasmodium of myxomycetes, which were considered at that time as primitive plants (or fungi). Today it is well established that myxomycetes are members of the Amoebozoa (Protista). In this study we compare the mobility of myxamoebae of 3 European species, Lycogala epidendrum (order Liceales), Tubulifera arachnoidea, and Trichia decipiens (order Trichiales). Using agar plates, on which 3 separate bacterial species were cultivated as prey organisms (Methylobacterium mesophilicum, Escherichia coli, Agrobacterium tumefaciens), we document large differences in cell motility between the myxomycetes investigated. In addition, we show that the 3 species of myxamoebae can be distinguished based on their average cell size. These data shed light on the mode of co-occurrence via differential substrate utilization in these members of the Amoebozoa. PMID- 26357878 TI - Factors associated with inpatient readmission among managed care enrollees with COPD. AB - OBJECTIVE: To assess factors associated with inpatient readmission among a US managed care population with chronic obstructive pulmonary disease (COPD). BACKGROUND: COPD is often accompanied by intermittent acute exacerbations, which may result in hospitalizations. These exacerbations are often associated with an increased frequency of subsequent exacerbations, which may lead to inpatient readmissions. METHODS: We assessed US managed care claims data for enrollees>=40 years old with an inpatient admission with a primary diagnosis of COPD (ICD-9-CM codes 491.xx, 492.xx or 496.xx) between 1 January 2010 and 31 December 2013 (discharge date of first observed inpatient admission defined the "index date"). Patients were required to be continuously enrolled for >=12 months before the index date. Two non-mutually exclusive cohorts were analyzed: (1) patients with >=30 days of post-index date continuous enrollment (to evaluate 30-day readmission) and (2) patients with >=90 days of post-index date continuous enrollment (to evaluate 90-day readmission). Logistic regression evaluated the association between patient characteristics and risk of 30- and 90-day COPD related and all-cause readmission. RESULTS: After applying selection criteria, 140,981 patients had >=30 days of enrollment post-index date, and 123,545 patients had >=90 days of enrollment post-index date. Within 30 days, nearly 20% of patients had an all-cause readmission and 7% had a COPD-related readmission. Within 90 days, 28% had an all-cause readmission and 12% had a COPD-related readmission. Logistic regression indicated that longer length of stay, older age, greater comorbidity burden, specific comorbidities and COPD complexity were associated with significantly greater odds of COPD-related 30- and 90-day readmission. Results for all-cause readmission were generally similar. CONCLUSIONS: Many of the factors associated with inpatient readmission documented here can be ascertained at discharge and may be used to inform discharge plans, with the end goal of improving patient outcomes, including reducing the risk of readmission. PMID- 26357879 TI - Socio-demographic, environmental and caring risk factors for childhood drowning deaths in Bangladesh. AB - BACKGROUND: Drowning contributes to incapacity and early death in many countries. In low- and middle-income countries, children are the most susceptible to fatalities. Over 50 % of the global drowning deaths occur among children aged under 15 years old with children aged between 1 and 4 years of age being most at risk. In Bangladesh, drowning rates are 10 to 20 times more than those in other developing countries. The object of this study is to determine the socio demographic, environmental and caring hazard issues for child drowning in Bangladesh. METHODS: A case-control study was conducted, with data collected from the Bangladesh Health and Injury Survey (BHIS) to identify the social-demographic and environmental factors associated with childhood drowning. The participants represented 171,366 households from seven divisions of Bangladesh-Dhaka, Rajshahi, Chittagong, Barisal, Sylhet, Khulna and Rangpur. The survey was conducted between January and December of 2003. A total of 141 children drowning were identified in the year preceding the survey. Data were analysed using descriptive statistics and logistic regression analysis. The odds ratios with 95% CI intervals were estimated for various associated factors for child drowning deaths. RESULTS: In Bangladesh, in 2003, the incidence of drowning deaths was 104.8 per 100,000 among those aged less than 5 years; 168.7 per 100,000 in rural areas; male 32.4 per 100,000; 112.7 per 100,000 between 10:00 a.m. and 2:00 p.m.; and cannot swim 134.9 per 100,000. The socio-demographic danger factors for child drowning deaths were: being male (OR = 1.45, 95% CI = 1.34-1.78), aged less than 5 years (OR = 2.89, 95% CI = 1.89-3.11), urban areas (OR = 0.67, 95% CI = 0.67 1.87), and mother being illiterate (OR = 1.69, 95% CI = 1.01-2.81). Significant environmental and caring factors included mother/caregiver not being the accompanying person (OR = 25.4, 95% CI = 14.4-45.3) and children cannot swim (OR = 4.5, 95% CI = 1.25-19.4). CONCLUSION: Drowning is the single largest reason for the mortality of children aged less than five years. There is a need to educate Bangladeshi parents and encourage behavioural change concerning supervision. The Government should use mass media to raise awareness about drowning among the community with a focus on rural areas. Policies should focus on increasing supervision by mothers/care persons, swimming skills, and should target illiterate mothers. Therefore, there is an immediate need for the Bangladeshi Government to address the problem of drowning. PMID- 26357880 TI - Dietary polyphenols and chromatin remodeling. AB - Polyphenols are the most abundant phytochemicals in fruits, vegetables, and plant derived beverages. Recent findings suggest that polyphenols display the ability to reverse adverse epigenetic regulation involved in pathological conditions, such as obesity, metabolic disorder, cardiovascular and neurodegenerative diseases, and various forms of cancer. Epigenetics, defined as heritable changes to the transcriptome, independent from those occurring in the genome, includes DNA methylation, histone modifications, and posttranscriptional gene regulation by noncoding RNAs. Sinergistically and cooperatively, these processes regulate gene expression by changing chromatin organization and DNA accessibility. Such induced epigenetic changes can be inherited during cell division, resulting in permanent maintenance of the acquired phenotype, but they may also occur throughout an individual life-course and may ultimately influence phenotypic outcomes (health and disease risk). In the last decade, a number of studies have shown that nutrients can affect metabolic traits by altering the structure of chromatin and directly regulate both transcription and translational processes. In this context, dietary polyphenol-targeted epigenetics becomes an attractive approach for disease prevention and intervention. Here, we will review how polyphenols, including flavonoids, curcuminoids, and stilbenes, modulate the establishment and maintenance of key epigenetic marks, thereby influencing gene expression and, hence, disease risk and health. PMID- 26357881 TI - Exacerbations, health services utilization, and costs in commercially-insured COPD patients treated with nebulized long-acting beta2-agonists. AB - OBJECTIVE: This retrospective cohort study compared exacerbations, health services utilization, and costs among chronic obstructive pulmonary disease (COPD) patients who received nebulized arformoterol or nebulized formoterol therapy. METHODS: Using PharMetrics Plus health plan claims, 417 nebulized long acting beta2-agonist (LABA) users meeting the study inclusion criteria were identified: had >=2 fills of nebulized arformoterol or nebulized formoterol from January 1, 2009, to December 31, 2011, adhered to using their index drug >=60% of the days during 1 year post-index, were >=35 years old and continuously enrolled 180 days pre- and 1 year post-index, and did not use a nebulized LABA or have an asthma diagnosis during the pre-index period. Descriptive and multivariate analyses were performed. RESULTS: A total of 274 nebulized arformoterol users and 143 nebulized formoterol users were identified with comparable demographic characteristics. However, significant differences were observed between the two groups in some clinical characteristics at index including comorbidities and use of antibiotics. At 1 year post-index, a lower proportion of nebulized arformoterol users had >=1 exacerbation compared to nebulized formoterol users (70.4% vs 80.4%; p = 0.028). Among patients with >=1 hospital admission, COPD related costs per inpatient stay were significantly lower for nebulized arformoterol users than nebulized formoterol users (median = $9542 vs $14,025; p = 0.009). After controlling for confounders, nebulized arformoterol users had 19% marginally lower risk of exacerbations than nebulized formoterol users (hazard ratio = 0.81, 95% confidence interval = 0.64-1.03; p < 0.084) and 14.4% marginally lower COPD-related total costs at 1 year post-index (p = 0.062), primarily related to fewer hospital readmissions (7.6% vs 12.2%) and lower average costs per readmission stay (median = $7392 vs $18 081; p = 0.006). CONCLUSIONS: This study suggests that the choice of nebulized LABA may influence COPD-related exacerbation occurrence and costs. Future studies with larger and more closely matched nebulized arformoterol and nebulized formoterol users are needed to confirm these findings. PMID- 26357882 TI - Food and feed chemical contaminants in the European Union: Regulatory, scientific, and technical issues concerning chemical contaminants occurrence, risk assessment, and risk management in the European Union. AB - A priority of the European Union is the control of risks possibly associated with chemical contaminants in food and undesirable substances in feed. Following an initial chapter describing the main contaminants detected in food and undesirable substances in feed in the EU, their main sources and the factors which affect their occurrence, the present review focuses on the "continous call for data" procedure that is a very effective system in place at EFSA to make possible the exposure assessment of specific contaminants and undesirable substances. Risk assessment of contaminants in food atances in feed is carried currently in the European Union by the CONTAM Panel of EFSA according to well defined methodologies and in collaboration with competent international organizations and with Member States. PMID- 26357883 TI - Acetyl-CoA synthetase is activated as part of the PDH-bypass in the oleaginous green alga Chlorella desiccata. AB - In a recent study, it has been shown that biosynthesis of triacylglycerol (TAG) in the oleaginous green alga Chlorella desiccata is preceded by a large increase in acetyl-coenzyme A (Ac-CoA) levels and by upregulation of plastidic pyruvate dehydrogenase (ptPDH). It was proposed that the capacity to accumulate high TAG critically depends on enhanced production of Ac-CoA. In this study, two alternative Ac-CoA producers-plastidic Ac-CoA synthase (ptACS) and ATP citrate lyase (ACL)-are shown to be upregulated prior to TAG accumulation under nitrogen deprivation in the oleaginous species C. desiccata, but not in the moderate TAG accumulators Dunaliella tertiolecta and Chlamydomonas reinhardtii. Measurements of endogenous acetate production and of radiolabelled acetate incorporation into lipids are consistent with the upregulation of ptACS, but suggest that its contribution to the overall TAG biosynthesis is negligible. Induction of ACS and production of endogenous acetate are correlated with activation of alcohol dehydrogenase, suggesting that the upregulation of ptACS is associated with activation of PDH-bypass in C. desiccata. It is proposed that activation of the PDH-bypass in C. desiccata is needed to enable a high rate of lipid biosynthesis under nitrogen deprivation by controlling the level of pyruvate reaching ptPHD and/or mtPDH. This may be an important parameter for massive TAG accumulation in microalgae. PMID- 26357884 TI - Identification, evolution, and expression partitioning of miRNAs in allopolyploid Brassica napus. AB - The recently published genome of Brassica napus offers for the first time the opportunity to gain insights into the genomic organization and the evolution of miRNAs in oilseed rape. In this study, 12 small RNA libraries from two B. napus cultivars (Tapidor and Ningyou7) and their four double-haploid lines were sequenced, employing the newly sequenced B. napus genome, together with genomes of its progenitors Brassica rapa and Brassica oleracea. A total of 645 miRNAs including 280 conserved and 365 novel miRNAs were identified. Comparative analysis revealed a high level of genomic conservation of MIRNAs (75.9%) between the subgenomes of B. napus and its two progenitors' genomes, and MIRNA lost/gain events (133) occurred in B. napus after its speciation. Furthermore, significant partitioning of miRNA expressions between the two subgenomes in B. napus was detected. The data of degradome sequencing, miRNA-mediated cleavage, and expression analyses support specific interactions between miRNAs and their targets in the modulation of diverse physiological processes in roots and leaves, as well as in biosynthesis of, for example, glucosinolates and lipids in oilseed rape. These data provide a first genome-wide view on the origin, evolution, and genomic organization of B. napus MIRNAs. PMID- 26357885 TI - A small indel mutation in an anthocyanin transporter causes variegated colouration of peach flowers. AB - The ornamental peach cultivar 'Hongbaihuatao (HBH)' can simultaneously bear pink, red, and variegated flowers on a single tree. Anthocyanin content in pink flowers is extremely low, being only 10% that of a red flower. Surprisingly, the expression of anthocyanin structural and potential regulatory genes in white flowers was not significantly lower than that in both pink and red flowers. However, proteomic analysis revealed a GST encoded by a gene-regulator involved in anthocyanin transport (Riant)-which is expressed in the red flower, but almost undetectable in the variegated flower. The Riant gene contains an insertion deletion (indel) polymorphism in exon 3. In white flowers, the Riant gene is interrupted by a 2-bp insertion in the last exon, which causes a frameshift and a premature stop codon. In contrast, both pink and red flowers that arise from bud sports are heterozygous for the Riant locus, with one functional allele due to the 2-bp deletion or a novel 1-bp insertion. Southern blot analysis indicated that the Riant gene occurs in a single copy in the peach genome and it is not interrupted by a transposon. The function of the Riant gene was confirmed by its ectopic expression in the Arabidopsis tt19 mutant, where it complements the anthocyanin phenotype, but not the proanthocyanidin pigmentation in seed coat. Collectively,these results indicate that a small indel mutation in the Riant gene, which is not the result of a transposon insertion or excision, causes variegated colouration of peach flowers. PMID- 26357886 TI - Development, validation, and application of a method for the GC-MS analysis of fipronil and three of its degradation products in samples of water, soil, and sediment. AB - A method for the identification and quantification of pesticide residues in water, soil, and sediment samples has been developed, validated, and applied for the analysis of real samples. The specificity was determined by the retention time and the confirmation and quantification of analyte ions. Linearity was demonstrated over the concentration range of 20 to 120 ug L(-1), and the correlation coefficients varied between 0.979 and 0.996, depending on the analytes. The recovery rates for all analytes in the studied matrix were between 86% and 112%. The intermediate precision and repeatability were determined at three concentration levels (40, 80, and 120 ug L(-1)), with the relative standard deviation for the intermediate precision between 1% and 5.3% and the repeatability varying between 2% and 13.4% for individual analytes. The limits of detection and quantification for fipronil, fipronil sulfide, fipronil-sulfone, and fipronil-desulfinyl were 6.2, 3.0, 6.6, and 4.0 ng L(-1) and 20.4, 9.0, 21.6, and 13.0 ng L(-1), respectively. The method developed was used in water, soil, and sediment samples containing 2.1 mg L(-1) and 1.2% and 5.3% of carbon, respectively. The recovery of pesticides in the environmental matrices varied from 88.26 to 109.63% for the lowest fortification level (40 and 100 ug kg(-1)), from 91.17 to 110.18% for the intermediate level (80 and 200 ug kg(-1)), and from 89.09 to 109.82% for the highest fortification level (120 and 300 ug kg(-1)). The relative standard deviation for the recovery of pesticides was under 15%. PMID- 26357887 TI - Multiresidue determination of pesticides in tea by gas chromatography-tandem mass spectrometry. AB - An efficient and reliable GC-MS/MS method for the multiresidue determination of pesticides in tea was developed by modifying the Japanese official multiresidue method. Sample preparation was carefully optimized for the efficient removal of coextracted matrix components. The optimal sample preparation procedure involved swelling of the sample in water; extraction with acetonitrile; removal of water by salting-out; and sequential cleanup by ODS, graphitized carbon black/primary secondary amine (GCB/PSA) and silica gel cartridges prior to GC-MS/MS analysis. The recoveries of 162 pesticides from fortified (at 0.01 mg kg(-1)) green tea, oolong tea, black tea and matcha (powdered green tea) were mostly (95-98% of the tested pesticides) within the range of 70-120%, with relative standard deviations of <20%. Poor recovery of triazole pesticides was considered to be due to low recovery from the silica gel cartridges. The test solutions obtained by the modified method contained relatively small amounts of pigments, caffeine and other matrix components and were cleaner than those obtained by the original Japanese official multiresidue method. No interfering peaks were observed in the blank chromatograms, indicating the high selectivity of the modified method. The overall results suggest that the developed method is suitable for the quantitative analysis of GC-amenable pesticide residues in tea. PMID- 26357889 TI - Contribution to the food products' analysis: A research and evaluation on the hemolytic effect of some pesticides used in Lebanon. AB - Pesticides are a real concern for the society as their use has become critical, leading sometimes to their accumulation as residues in fruits and vegetables. After examining the pesticides sold in Northern Lebanon, this study is focused on the analysis and identification of pesticides residues in fruits and vegetables that are harvested in this region and treated with the locally sold pesticides. Results show: first, (i) a use of Zineb by the name of another pesticide Micronized Sulfur to avoid prosecution; (ii) a significant presence of Metalaxyl in lemons and oranges; (iii) a significant presence of Trifluralin in strawberries; and (iv) a significant presence of Zineb in lemons and tomatoes. Second, with the use of hemolytic tests on human blood results show: (i) a critical concentration and a significant hemolytic effect of some pesticides used in Lebanon; and (ii) an absence of hemolytic effect in the collected fractions of the different analyzed fruit extracts containing pesticides. Finally, this work is the first step for pesticides' analysis in vegetables and fruits in Lebanon, initiating a wider analytical study in order to control and examine the use of pesticides which, according to our results, could have an adverse effect on human health over a long term. PMID- 26357888 TI - Adsorption of simazine on zeolite H-Y and sol-gel technique manufactured porous silica: A comparative study in model and natural waters. AB - In this work, we studied the removal of simazine from both a model and well water by adsorption on two different adsorbents: zeolite H-Y and a porous silica made in the laboratory by using the sol-gel technique. The pH dependence of the adsorption process and the isotherms and pseudo-isotherms of adsorption were studied. Moreover, an iterative process of simazine removal from both the model and well water, which allowed us to bring the residual simazine concentration below the maximum concentration (0.05 mg L(-1)) of agrochemicals in wastewater to be released in surface waters or in sink allowed by Italian laws, was proposed. The results obtained were very interesting and the conclusions drawn from them partly differed from what could reasonably be expected. PMID- 26357890 TI - Effects of temperature, pH and NaCl content on in vitro putrescine and cadaverine production through the growth of Serratia marcescens CCM 303. AB - The aim of this study was to evaluate the combined effect of temperature (10, 20 and 37 degrees C), pH (4, 5, 6, 7 and 8), and NaCl content (0, 1, 3, 4, 5 and 6% w/v) on the growth and putrescine and cadaverine production of Serratia marcescens CCM 303 under model conditions. The decarboxylase activity of S. marcescens was monitored in broth after cultivation. The cultivation medium was enriched with selected amino acids (ornithine, arginine and lysine; 0.2% w/v each) serving as precursors of biogenic amines. Levels of putrescine and cadaverine in broth were analysed by high-performance liquid chromatography after pre-column derivatisation with o-phthalaldehyde reagent. S. marcescens produced higher amounts of putrescine (up to 2096.8 mg L(-1)) compared to cadaverine content (up to 343.3 mg L(-1)) in all cultivation media. The highest putrescine and cadaverine concentrations were reached during cultivation at 10-20 degrees C, pH 5-7 and NaCl content 1-3% w/v. On the other hand, the highest BAs production of individual cell (recalculated based on a cell; so called "yield factor") was observed at 10 degrees C, pH 4 and salt concentration 3-5% w/v as a response to environmental stress. PMID- 26357891 TI - Physiological effects of tetracycline antibiotic pollutants on non-target aquatic Microcystis aeruginosa. AB - This study aimed to evaluate the aquatic toxicity of three typical tetracycline antibiotics, including tetracycline, oxytetracycline, and chlortetracycline, on the cyanobacterium Microcystis aeruginosa. The cell density, chlorophyll a content, protein content, and enzymatic antioxidant activities were determined. The results showed that the cell growth was significantly inhibited by the three compounds at a low concentration. The chlorophyll a and protein content decreased significantly after exposure to 0.05 mg L(-1) of each compound for 9 d. When exposed to 0.2-1 mg L(-1) of tetracycline, the superoxide dismutase (SOD) activity increased, but peroxidase (POD) and catalase (CAT) activities decreased. In contrast, when exposed to oxytetracycline and chlortetracycline at different concentrations ranging from 0.2 to 1 mg L(-1) and from 0.01 to 0.05 mg L(-1), the SOD activity decreased, but the POD and CAT activities increased. These findings indicate that tetracycline antibiotics influence cell growth and protein synthesis, and they also induce oxidative stress in M. aeruginosa at environmentally similar concentrations. Thus, this study may provide further insights into the toxic effects of tetracycline antibiotics and the controlled use of antibiotics. PMID- 26357892 TI - The application of HPLC ESI MS in the investigation of the flavonoids and flavonoid glycosides of a Caribbean Lamiaceae plant with potential for bioaccumulation. AB - As part of an exchange technology program between the government of Barbados and Environment Canada, methanolic and aqueous extracts from the flavonoid-rich Lamiaceae family were characterized using negative-ion electrospray mass spectrometry. The species investigated is part of the Caribbean Pharmacopoeia, and is used for a variety of health issues, including colds, flu, diabetes, and hypertension. The extracts were investigated for structural elucidation of phenolics, identification of chemical taxonomic profile, and evidence of bio accumulator potential. The methanolic and aqueous leaf extracts of Plectranthus amboinicus yielded rosmarinic acid, ladanein, cirsimaritin, and other methoxylated flavonoids. This genus also shows a tendency to form conjugates with monosaccharides, including glucose, galactose, and rhamnose. The aqueous extract yielded four isomeric rhamnosides. The formation of conjugates by Plectranthus amboinicus is thus evidence of high bioaccumulator significance. PMID- 26357893 TI - Studies on the drug resistance profile of Enterococcus faecium distributed from poultry retailers to hospitals. AB - The multidrug resistant Enterococcus faecium (MEF) strains originating from farm animals are proliferating at a substantial pace to impact downstream food chains and could reach hospitals. This study was conducted to elucidate the drug susceptibility profile of MEF strains collected from poultry products in Ann Arbor, MI area and clinical settings from Michigan State Lab and Moffitt Cancer Center (MCC) in Florida. Presumptive positive Enterococcus isolates at species level were identified by Matrix Assisted Laser Desorption/Ionization Time-of Flight (MALDI-TOF) analysis. The antibiotic susceptibility profile for both poultry and clinical strains was determined by the Thermo Scientific's Sensititre conform to the National Committee for Clinical Laboratory Standards (NCCLS) and validated via quantitative real-time PCR (qPCR) methods. Out of 50 poultry samples (Turkey: n = 30; Chicken: n = 20), 36 samples were positive for Enterococcus species from which 20.83% were identified as E. faecium. All the E. faecium isolates were multidrug resistant and displayed resistance to the last alternative drug, quinupristin/dalfopristin (QD) used to treat vancomycin resistant E. faecium (VRE) in hospitals. Results indicate the presence of MEF strains in food animals and clinical settings that are also resistant to QD. PMID- 26357894 TI - Human exposure to heavy metals and possible public health risks via consumption of wild edible mushrooms from Slovak Paradise National Park, Slovakia. AB - The contamination level of 92 samples (12 species) of wild edible mushrooms and underlying substrates with heavy metals (Cd, Cu, Hg, Pb and Zn) in the Slovak Paradise National Park that borders with a region of historical mining and processing of polymetallic ores, were determined. The collected samples were analyzed using of atomic absorption spectrophotometry. The metals were determined separately in hymenophore (H) and rest of fruit bodies (RFB). Bioaccumulation factor as well as ratio of metal content in H and RFB were calculated. Cadmium and lead contents in hymenophore exceeded statutory limits of the EU (Cd: 0.5 mg/kg dry weight (dw), Pb: 1.0 mg/kg dw) for edible mushrooms in 96% and 83% of the samples, respectively. The risk from the consumption of the collected mushroom species was calculated based on the provisionally tolerable weekly intake (PTWI) values, and the highest health risk arising with consumption of particularly Macrolepiota procera, Marasmius oreades and Russula vesca from the observed area was demonstrated. It was shown that average weekly consumption of tested mushrooms species results the threat of exceeding of PTWI limits in the case of cadmium values (by 164%, 86% and 4% of PTWI for M. oreades, R. vesca and R. puellaris, respectively) and of mercury (by 96% of PTWI for M. procera) but not lead. PMID- 26357895 TI - Specialty pharmaceuticals and the quest for better outcomes. AB - Over the past decade, the healthcare system has seen significant growth in the number of products, pathways, and modes of treatment administration for a number of costly conditions. Many of these products are biologic agents, classified as specialty pharmaceuticals, and are distributed through specialty pharmacies. The increasing use of these expensive medications and their growing costs raise the simple question, can payers and purchasers afford to keep doing business as usual? In addition, confusion exists as to what "outcomes" are relevant for these conditions treated using specialty medications. Available information on outcomes, treatments, and pathways from multiple sources can overload clinicians and the treatment team, making it difficult to select - and receive reimbursement for - the most appropriate regimens. This article offers an approach to understanding some of the unique challenges posed in evaluating the value of specialty pharmaceuticals. PMID- 26357896 TI - Nebulised hypertonic saline (3%) among children with mild to moderately severe bronchiolitis--a double blind randomized controlled trial. AB - BACKGROUND: To Assess the efficacy of nebulised hypertonic saline (HS) (3%) among children with mild to moderately severe bronchiolitis. METHODS: Infants aged 6 weeks to 24 months, with a first episode of wheezing and Clinical Severity scores (Arch Dis Child 67:289-93, 1992) between 1 and 8, were enrolled over 4 months duration. Those with severe disease, co-morbidities, prior wheezing, recent bronchodilator and steroid use were excluded. Patients were randomized in a double-blind fashion, to receive two doses of nebulized 3% HS (Group 1) or 0.9% normal saline (Group 2) with 1.5 mg of L-Epineprine, delivered 30 min apart. Parents were contacted at 24 h and 7 days. The principal outcome measure was the mean change in clinical severity score at the end of 2 h of observation. RESULTS: A total of 100 infants (mean age 9.6 months, range 2-23 months; 61 % males) were enrolled. Patients in both groups had mild to moderately severe disease at presentation. On an intention-to-treat basis, the infants in the HS group had a significant reduction (3.57 +/- 1.41) in the mean clinical severity score compared to those in the NS group (2.26 +/- 1.15); [p < 0.001; CI: 0.78-1.82]. More children in the HS group (n = 35/50; 70.0%) were eligible for ER/OPD discharge at the end of 2 h than those in the NS group (n = 15/50; 30%; p < 0.001), and less likely to need a hospital re-visit (n = 5/50; 10.0%) in the next 24 h as compared to the NS group (n = 15/50, 30.0%; p < 0.001). The treatment was well tolerated, with no adverse effects. CONCLUSIONS: Nebulized 3% HS is effective, safe and superior to normal saline for outpatient management of infants with mild to moderately severe viral bronchiolitis in improving Clinical Severity Scores, facilitating early Out-Patient Department discharge and preventing hospital re-visits and admissions in the 24 h of presentation. TRIAL REGISTRATION: Clinicaltrials.gov NCTID012766821. Registered on January 12, 2011. PMID- 26357897 TI - Microflora of processed cheese and the factors affecting it. AB - The basic raw materials for the production of processed cheese are natural cheese which is treated by heat with the addition of emulsifying salts. From a point of view of the melting temperatures used (and the pH-value of the product), the course of processed cheese production can be considered "pasteurisation of cheese." During the melting process, the majority of vegetative forms of microorganisms, including bacteria of the family Enterobacteriaceae, are inactivated. The melting temperatures are not sufficient to kill the endospores, which survive the process but are often weakened. From a microbiological point of view, the biggest contamination problem of processed cheese is caused by gram positive spore-forming rod-shaped bacteria of the genera Bacillus, Geobacillus, and Clostridium. Other factors affecting the shelf-life and quality of processed cheese are mainly the microbiological quality of the raw materials used, strict hygienic conditions during the manufacturing process as well as the type of packaging materials and storage conditions. The quality of processed cheese is not only dependent on the ingredients used but also on other parameters such as the value of water activity of the processed cheese, its pH-value, the presence of salts and emulsifying salts and the amount of fat in the product. PMID- 26357898 TI - The accuracy of presepsin (sCD14-ST) for the diagnosis of sepsis in adults: a meta-analysis. AB - INTRODUCTION: The early diagnosis of sepsis remains a challenge. Recently, soluble cluster of differentiation 14 subtype (sCD14-ST), also known as presepsin, has been identified as a potential biomarker of sepsis. We performed a meta-analysis to assess the diagnostic accuracy of presepsin for sepsis in patients with systemic inflammation. METHODS: We systematically searched the PubMed, Embase, Web of Knowledge and Cochrane databases. Studies were included if they assessed the diagnostic accuracy of presepsin for sepsis in adult patients with systemic inflammatory response syndrome (SIRS). Furthermore, a 2 * 2 contingency table was constructed based on these results. Two authors independently judged the studies and extracted the data. The diagnostic accuracy of presepsin in sepsis was calculated using a bivariate meta-analysis model. The Q-test and I (2) index were used to test the heterogeneity. RESULTS: Eight studies involving a total of 1,815 patients were included in the present study. The pooled sensitivity, specificity, diagnostic odds ratio, positive likelihood ratio and negative likelihood ratio were 0.86 (95% CI: 0.79-0.91), 0.78 (95% CI: 0.68-0.85), 22 (95% CI: 10-48), 3.8 (95% CI: 2.6-5.7), and 0.18 (95% CI: 0.11 0.28), respectively. The area under the summary receiver operator characteristic curve was 0.89 (95% CI: 0.86-0.92). Meta-regression analysis revealed that consecutive patient selection, sample size and setting significantly accounted for the heterogeneity of sensitivity. CONCLUSIONS: Our findings suggest that presepsin exhibits very good diagnostic accuracy (AUC=0.89) for the diagnosis for sepsis. Nevertheless, an overall assessment of all the clinical indexes for sepsis diagnosis and continual re-evaluation of presepsin during the course of the disease are needed. PMID- 26357900 TI - The Healthy Effects of Strawberry Polyphenols: Which Strategy behind Antioxidant Capacity? AB - Current evidence indicates that the consumption of strawberries, a natural source of a wide range of nutritive and bioactive compounds, is associated with the prevention and improvement of chronic-degenerative diseases. Studies involving cells and animals provide evidence on the anti-inflammatory, anticarcinogenic and antiproliferative activity of the strawberry. Epidemiological and clinical studies demonstrate that its acute consumption increases plasma antioxidant capacity, improves circulating inflammatory markers and ameliorates postprandial glycemic response. At the same time, a protracted intake reduces chronic inflammation and improves plasma lipid profile, supporting cardiovascular health, especially in individuals with increased risk for metabolic syndrome. To explain these beneficial effects, much attention has been paid in the past to the antioxidant properties of strawberry polyphenols. However, recent research has shown that their biological and functional activities are related not only to the antioxidant capacity but also to the modulation of many cellular pathways involved in metabolism, survival, proliferation, and antioxidant defenses. The aim of this review is to update and discuss the molecular and cellular mechanisms proposed in recent studies to elucidate the healthy effects of strawberry polyphenols against the most common chronic diseases, such as cancer, cardiovascular diseases, metabolic syndrome, and inflammation. PMID- 26357899 TI - HDAC5-mTORC1 Interaction in Differential Regulation of Ghrelin and Nucleobindin 2 (NUCB2)/Nesfatin-1. AB - Sodium valporate (VPA), a broad-spectrum inhibitor of histone deacetylases (HDACs), increased ghrelin whereas decreased nesfatin-1 in mice fed normal chow diet or high-fat diet. Alterations in ghrelin and nucleobindin 2/nesfatin-1 were mediated by HDAC5 but not HDAC4. Activation of mTORC1 significantly attenuated the effect of VPA on ghrelin and nesfatin-1 levels. HDAC5 coimmunoprecipitated with raptor. Inhibition of HDAC5 by VPA, trichostatin A, or siHDAC5 markedly increased acetylation of raptor Lys840 and subsequent phosphorylation of raptor Ser792, resulting in suppression of mTORC1 signaling. A raptor mutant lacking the Lys840 acetylation site showed a decrement in phosphorylation of raptor Ser792 and subsequent increase in mTORC1 signaling. These alterations were associated with reciprocal changes in ghrelin and nucleobindin 2/nesfatin-1 expression. These findings reveal HDAC5-mTORC1 signaling as a novel mechanism in the differential regulation of gastric ghrelin and nesfatin-1. PMID- 26357901 TI - Erratum. AB - Journal of Heredity, Volume 105, Issue 6 . The issue should start on page 835. The publisher regrets this error. The online version of this issue has been corrected. PMID- 26357903 TI - The effect of positive affect on conflict resolution: Modulated by approach motivational intensity. AB - The motivational dimensional model of affect proposes that the influence of positive affect on cognitive processing is modulated by approach-motivational intensity. The present research extended this model by examining the influence of positive affect varying in approach-motivational intensity on conflict resolution the ability to resolve interference from task-irrelevant distractors in order to focus on the target. The global-local task (Experiment 1) and letter-Flanker task (Experiment 2) were used to measure conflict resolution. Additionally, the 4:2 mapping design that assigns two kinds of task-relevant stimuli to one response key and two more to another response key was used in these two tasks to dissociate stimulus and response conflict. Results showed that positive affect varying in approach motivation had opposite influences on conflict resolution. The opposite influences are primarily reflected in low approach-motivated positive affect impairing, while high approach-motivated positive affect facilitating the resolution of response conflict. Conversely, the stimulus conflict was slightly influenced. These findings highlight the utility of distinguishing stimulus and response conflict in future research. PMID- 26357902 TI - Psychostimulant prescribing trends in a paediatric population in Ireland: a national cohort study. AB - BACKGROUND: Psychotropic paediatric prescribing trends are increasing internationally. The aim of this study is to examine the prevalence and secular trends in psychotropic prescribing in Irish children and adolescents between 2002 and 2011. METHODS: Data was obtained from the Irish General Medical Services (GMS) scheme pharmacy claims database from the Health Service Executive Primary Care Reimbursement Services (HSE-PCRS). Prescribing rates per 1000 eligible population and associated 95% confidence intervals (CIs) were calculated across years (2002-2011), age groups (0-4, 5-11, 12-15 years) and gender. Rates of concomitant prescriptions for psycholeptics and antidepressants were also examined. The total expenditure costs were calculated and expressed as a percentage of the cost of all prescriptions for this age group (<= 15 years). RESULTS: In 2002, 3.77/1000 GMS population (95% CI: 3.53-4.01) received at least one psychostimulant prescription and this rate increased to 8.63/1000 GMS population (95% CI: 8.34-8.92) in 2011. Methylphenidate was the most frequently prescribed psychostimulant. For both males and females the prevalence of medication use was highest among the 12-15 year old group. On average, a psycholeptic medication was prescribed to 8% of all psychostimulant users and an antidepressant was concomitantly prescribed on average to 2%. Total expenditure rose from ?89,254 in 2002 to ?1,532,016 in 2011. CONCLUSIONS: The rate and cost of psychostimulant prescribing among GMS children and adolescents in Ireland increased significantly between 2002 and 2011. Further research is necessary to assess the safety, efficacy and economic impact of concomitant psychotropic prescribing in this population. PMID- 26357904 TI - Use of encapsulated bacteriophages to enhance farm to fork food safety. AB - Bacteriophages have been successfully applied to control the growth of pathogens in foods and to reduce the colonization and shedding of pathogens by food animals. They are set to play a dominant role in food safety in the future. However, many food-processing operations and the microenvironments in food animals' guts inactivate phages and reduce their infectivity. Encapsulation technologies have been used successfully to protect phages against extreme environments, and have been shown to preserve their activity and enable their release in targeted environments. A number of encapsulation technologies have shown potential for use with bacteriophages. This review discusses the current state of knowledge about the use of encapsulation technologies with bacteriophages to control pathogens in foods and food animals. PMID- 26357905 TI - MAGIC maize: a new resource for plant genetics. AB - A multiparent advanced-generation intercross population of maize has been developed to help plant geneticists identify sequence variants affecting important agricultural traits. PMID- 26357906 TI - An improved spatial span test of visuospatial memory. AB - In the widely used Corsi Block Test and Wechsler Spatial Span Tests, participants must reproduce sequences of blocks in the order touched by the examiner until two trials are missed at the same sequence length. The examiner records either the maximum number of blocks correctly reported or the total number of correct lists. Here, we describe a computerized spatial span test (C-SST) that uses psychophysical procedures to quantify visuospatial mean span (MnS) with sub-digit precision. Results from 187 participants ranging in age from 18 to 82 years showed that accuracy declined gradually with list length around the MnS (by ~30% per item). Simulation studies revealed high variance and biases in CBT and Wechsler measures, and demonstrated that the C-SST provided the most accurate estimate of true span (i.e., the sequence length producing 50% correct). MnS declined more rapidly with age than mean digit span (MnDS) measured in the same participants. Response times correlated with both MnS and MnDS scores. Error analysis showed that omission and transposition errors predominated, with weaker primacy and recency effects in spatial span than digit span testing. The C-SST improves the precision of spatial span testing and reveals significant differences between visuospatial and verbal working memory. PMID- 26357907 TI - Advantages and disadvantages for receiving Internet-based HIV/AIDS interventions at home or at community-based organizations. AB - Within recent years, public health interventions have become technology based to reflect the digital age we currently live in and appeal to the public in innovative and novel ways. The Internet breaks down boundaries distance imposes and increases our ability to reach and connect with people. Internet-based interventions have the potential to expand access to effective behavioral interventions (EBIs). The US National HIV/AIDS Strategy states that people living with HIV should have access to EBIs such as healthy relationships (HR) to help them develop safe sex and disclosure skills. However, access to HR is limited across the country, especially for people in remote or rural areas. Internet based healthy relationships video groups (HR-VG) delivered at home or community based organizations (CBOs) can possibly expand access. This study assesses the preferences of women living with HIV (WLH) for participation in HR-VG among 21 WLH who participated in a randomized control trial (RCT) testing HR-VG and completed open-ended semi-structured telephone interviews. Transcripts were thematically analyzed to determine advantages and disadvantages of home or CBO delivery of HR-VG. Themes relating to convenience, technology access, privacy, distractions, HIV serostatus disclosure, and social opportunities were identified as advantages or disadvantages to participating in HR-VG at each location. Overall, privacy was the most salient concern of accessing HR-VG at home or at a CBO. Considering the concerns expressed by WLH, further studies are needed to assess how an Internet-based intervention delivered at home for WLH can maintain privacy while being cost effective. PMID- 26357908 TI - Erratum to: The clinical and cost effectiveness of group art therapy for people with non-psychotic mental health disorders: a systematic review and cost effectiveness analysis. PMID- 26357909 TI - Escape From Monoclonal Antibody Neutralization Affects Henipavirus Fitness In Vitro and In Vivo. AB - Henipaviruses are zoonotic viruses that can cause severe and acute respiratory diseases and encephalitis in humans. To date, no vaccine or treatments are approved for human use. The presence of neutralizing antibodies is a strong correlate of protection against lethal disease in animals. However, since RNA viruses are prone to high mutation rates, the possibility that these viruses will escape neutralization remains a potential concern. In the present study, we generated neutralization-escape mutants, using 6 different monoclonal antibodies, and studied the effect of these neutralization-escape mutations on in vitro and in vivo fitness. These data provide a mechanism for overcoming neutralization escape by use of cocktails of cross-neutralizing monoclonal antibodies that recognize residues within the glycoprotein that are important for virus replication and virulence. PMID- 26357910 TI - The complete chloroplast genome sequence of Hibiscus syriacus. AB - The complete chloroplast genome sequence of Hibiscus syriacus L. is presented in this study. The genome is composed of 161 019 bp in length, with a typical circular structure containing a pair of inverted repeats of 25 745 bp of length separated by a large single-copy region and a small single-copy region of 89 698 bp and 19 831 bp of length, respectively. The overall GC content is 36.8%. One hundred and fourteen genes were annotated, including 81 protein-coding genes, 4 ribosomal RNA genes and 29 transfer RNA genes. PMID- 26357911 TI - Brain activation underlying threat detection to targets of different races. AB - The current study examined blood oxygen level-dependent signal underlying racial differences in threat detection. During functional magnetic resonance imaging, participants determined whether pictures of Black or White individuals held weapons. They were instructed to make shoot responses when the picture showed armed individuals but don't shoot responses to unarmed individuals, with the cost of not shooting armed individuals being greater than that of shooting unarmed individuals. Participants were faster to shoot armed Blacks than Whites, but faster in making don't shoot responses to unarmed Whites than Blacks. Brain activity differed to armed versus unarmed targets depending on target race, suggesting different mechanisms underlying threat versus safety decisions. Anterior cingulate cortex was preferentially engaged for unarmed Whites than Blacks. Parietal and visual cortical regions exhibited greater activity for armed Blacks than Whites. Seed-based functional connectivity of the amygdala revealed greater coherence with parietal and visual cortices for armed Blacks than Whites. Furthermore, greater implicit Black-danger associations were associated with increased amygdala activation to armed Blacks, compared to armed Whites. Our results suggest that different neural mechanisms may underlie racial differences in responses to armed versus unarmed targets. PMID- 26357912 TI - Lifelong antiretroviral therapy or HIV cure: The benefits for the individual patient. AB - There are an estimated 35 million people living with human immunodeficiency virus (HIV) globally, 19 million of whom are unaware of their HIV status and, in the absence of antiretroviral therapy (ART), will have a shortened life expectancy. Although ART remains the "gold standard" for treatment of HIV infection, the requirement for lifelong treatment poses multiple challenges for the patient. These include stigma, an untenable pill burden, side effects, and the threat of viral resistance in the case of non-compliance. This review evaluates the challenges of accessing, delivering, and sustaining ART for people living with HIV and will discuss the case for pursuing a goal of HIV cure, the potential benefits of such a cure for the individual patient, and the current potential candidates for such a cure. PMID- 26357914 TI - Complete mitochondrial genomes of the white-browed piculet (Sasia ochracea, Picidae) and pale-billed woodpecker (Campephilus guatemalensis, Picidae). AB - The mitochondrial genome of the white-browed piculet Sasia ochracea (Piciformes, Picidae) and the pale-billed woodpecker Campephilus guatemalensis (Piciformes, Picidae) were sequenced using a mixed strategy of Sanger and next-generation sequencing methods. The size of the circular mitochondrial genomes were 16 908 and 16 856 bp, respectively, and include 13 protein-coding genes, 22 transfer tRNAs, 2 ribosomal RNAs, a control region and a reduced pseudo control region. The functional control region was located between the tRNAThr and tRNAPro, as found in the two other Piciformes for which complete mtDNA data are available. The length of the pseudo-control region in the white-browed piculet (103 bp) and pale-billed woodpecker (87 bp) is similar to the size of that region in Dryocopus pileatus (60 bp) and much shorter that the length of this region in Pteroglossus azara (1493 bp), suggesting that size reduction occurred before the last common ancestor of the piculets and woodpeckers. PMID- 26357915 TI - Assessing the criminal capacity of children: a challenge to the capacity of mental health professionals. AB - With increasing numbers of juveniles accused of serious crimes international concern is growing around the procedural consequences for affected individuals within the context of the law and criminal justice. Issues of culpability in children and adolescents are often raised, with much deliberation and insufficient agreement among legal and child development experts. Exactly when and to what extent juveniles can be held responsible for their action is a matter requiring careful consideration to avoid substantial erring in either direction. Although some international guiding standards and principles have been established, these are rather broad and unable to provide specific prescriptions. In addition, the assessment of criminal capacity in juveniles is a complex task, and one that is not wholly without reliability and validity problems. As in the case of South Africa and a few other countries, mental health specialists are often tasked with conducting developmental assessments to provide courts with expert evidence regarding criminal capacity. This paper examines the concept of criminal capacity in the context of the theory, controversies and challenges that affect this area of psychological focus. PMID- 26357913 TI - Genetic properties of the MAGIC maize population: a new platform for high definition QTL mapping in Zea mays. AB - BACKGROUND: Maize (Zea mays) is a globally produced crop with broad genetic and phenotypic variation. New tools that improve our understanding of the genetic basis of quantitative traits are needed to guide predictive crop breeding. We have produced the first balanced multi-parental population in maize, a tool that provides high diversity and dense recombination events to allow routine quantitative trait loci (QTL) mapping in maize. RESULTS: We produced 1,636 MAGIC maize recombinant inbred lines derived from eight genetically diverse founder lines. The characterization of 529 MAGIC maize lines shows that the population is a balanced, evenly differentiated mosaic of the eight founders, with mapping power and resolution strengthened by high minor allele frequencies and a fast decay of linkage disequilibrium. We show how MAGIC maize may find strong candidate genes by incorporating genome sequencing and transcriptomics data. We discuss three QTL for grain yield and three for flowering time, reporting candidate genes. Power simulations show that subsets of MAGIC maize might achieve high-power and high-definition QTL mapping. CONCLUSIONS: We demonstrate MAGIC maize's value in identifying the genetic bases of complex traits of agronomic relevance. The design of MAGIC maize allows the accumulation of sequencing and transcriptomics layers to guide the identification of candidate genes for a number of maize traits at different developmental stages. The characterization of the full MAGIC maize population will lead to higher power and definition in QTL mapping, and lay the basis for improved understanding of maize phenotypes, heterosis included. MAGIC maize is available to researchers. PMID- 26357916 TI - Clinical correlates of first episode early onset psychosis in KwaZulu-Natal, South Africa. AB - BACKGROUND: The study of first episode early onset psychosis can yield many clues to understanding the early development of psychosis and guide interventions to decrease psychosis risk and improve outcome. The aim of the study was to investigate the socio-demographic profile and clinical correlates in early onset psychosis. METHOD: Forty-five adolescents with first episode early onset psychosis were assessed by a clinical interview, socio-demographic questionnaire, the Positive and Negative Syndrome Scale (PANSS), Symptom Onset in Schizophrenia (SOS) score, the World Health Organization Alcohol, Smoking and Substance Involvement Screening Test (WHO ASSIST) questionnaire for substance misuse and a urine cannabis level. RESULTS: The mean age of the respondents was 15.9 years (SD 1.8, range 10-18 years). Thirty-one (69%) were male. There was a poor recognition of the prodromal period in 22 (49%) patients and caregivers. The mean duration of untreated psychosis (DUP) was 27.2 weeks (SD 56.7). There was a negative correlation between DUP and age of onset (p<0.05). Mean age at onset of psychosis (males 15.7 years, SD 2.2, and females 15.3 years, SD 2.6) and mean age of presentation (males 16.0 years, SD 1.8, and females 15.5 years, SD 1.7) was slightly younger in the females than males, but not statistically significant. A total of 25 (56%) adolescents reported lifetime cannabis use and 24 (96%) were male. CONCLUSION: Symptoms of the prodromal period were poorly recognised. The mean DUP suggests a significant delay in treatment and younger children had a longer DUP. The gender differences in presentation (marginal) and substance use (highly significant) suggests that there may be different environmental risk factors for males and females in early onset psychosis or that early onset psychosis is more genetically homogenous and less dependent on environmental triggers. PMID- 26357917 TI - Psychiatric services for preschoolers: an emerging need. AB - OBJECTIVE: To describe clinical presentation and service requirements for those under six years of age referred to a specialised child and adolescent psychiatry unit. METHOD: This study used a retrospective review of preschoolers, six years and younger, assessed at a child, family and adolescent psychiatric unit (January 2006 to 31 December 2010). Data analysis established predominant diagnoses (prevalence percentages) and correlations and associations (diagnoses and a range of clinical variables - Fischer's exact test and chi-square test). RESULTS: The sample comprised 149 subjects. Males predominated (77.2%; N = 115). Mean age of presentation was 54 months (SD=12.59). Children were referred predominantly by health professionals (36.9%; N = 55) and schools (20.8%; N = 31). Attention deficit hyperactivity disorder (ADHD) was the most common diagnosis (52.8%; N = 70), and was not over-represented amongst boys. Girls mostly presented with anxiety disorders (44.1%; 15/34) and reactive attachment disorder (RAD) (35.3%; 12/34), and boys mostly with pervasive developmental disorders (PDD) (26%; 30/115). Psychometric testing was frequent (68.5%; N = 102). Pharmacological intervention was common (46.3%; N = 69). The defaulting rate after initial assessment was high (42.1%; 48/114). CONCLUSION: The study demonstrates the existence of psychiatric illness in this sample, highlighting service needs. Vulnerability of this age group and limited sub-specialist resources emphasise the need for the development of community services leading to early recognition and intervention. PMID- 26357918 TI - Hazardous, harmful and dependent drinking in hostel-dwelling students at the University of the Free State, Bloemfontein: a cross-sectional study. AB - OBJECTIVE: This study was conducted to determine the prevalence of hazardous, harmful and dependent drinking among hostel-dwelling students on the main campus of the University of the Free State (UFS), and the influence of sex and academic year on the habit. METHOD: A quarter of all hostel-dwelling students of UFS were selected by systematic random sampling. Willing participants completed a questionnaire comprising a demographic section and the Alcohol Use Disorders Identification Test (AUDIT). RESULTS: Of the 339 participants with total AUDIT scores, 15.6% exhibited hazardous drinking, 4.1% harmful drinking and 5.6% alcohol dependence. Male students had a statistically significant higher prevalence (32.8%) of hazardous, harmful or dependent drinking than female students (18.9%). Women, however, are biologically more vulnerable to the ill effects of alcohol due to altered pharmacokinetics and pharmacodynamics of alcohol. In addition, intoxicated women suffer more biological and social risks. When the cut-off point for hazardous drinking was adapted to account for the increased biological vulnerability of women, the difference between female and male participants was no longer significant. First year male students were less likely to engage in unsafe drinking than senior students. Female students in the alcohol dependent category showed an increasing trend over advancing academic year. CONCLUSIONS: Follow-up studies are needed to confirm whether a significant difference in hazardous drinking of first year male students compared to seniors reflects the influence of university policy or merely precedes drinking acculturation. PMID- 26357919 TI - Examining empathy and its association with aggression in young Western Cape children. AB - OBJECTIVE: In a context of disturbing rates of violent crime, this pilot study initiated examination of the association between empathy and aggressive behaviour in young Western Cape children. Establishing which empathy measures are appropriate for our context was a primary concern. METHOD: To capture various aspects of empathy in young children we adopted a multi-method approach. We examined empathy scores in 65 lower middle socio-economic status (SES) English speaking Grade 1 pupils (6.0-8.0 years old) and their association with aggressive externalising behaviour. RESULTS: Parent report measures of callous-unemotional traits and aggression performed well, however, the Griffith Empathy Measure, a well-established parent report scale, proved problematic. Empathy scores, particularly those for callous-unemotional traits, were associated with aggression. We also found several associations between aspects of empathy, consistent with the international literature. Cognitive empathy, as measured by first-order false belief reasoning, was not well established, suggesting that other more complex social cognitive tasks were inappropriate for this age group in our context. CONCLUSION: The association between empathy and aggression warrants further investigation in this context. Appropriate measures for the South African context must be utilised. PMID- 26357920 TI - "They laugh when I sing": perceived effects of caregiver social support on child wellbeing among South African caregivers of children. AB - OBJECTIVE: Social support provided to caregivers of children has been shown to be protective for caregiver health, parenting and child psychosocial outcomes. However, little work in Southern Africa provides insight on the relationship between caregiver social support and child wellbeing. This report discusses exploratory qualitative findings from a larger mixed methods study, on caregivers' perceptions of the pathways through which received support affects their children's lives. METHODS: In-depth semi-structured interviews were conducted with 24 adult primary caregivers of children (aged 10-17 years) living in an HIV-endemic resource-constrained urban South African community. Thematic analysis of the data was supported by NVivo. RESULTS: Caregivers perceived the social support they received to positively affect their children's health and behaviour, both directly and through a positive influence on their (the caregivers') mental health, parenting and decision making. Information, advice and encouragement emerged as key types of support explaining perceived effects. CONCLUSION: Future research should continue to explore pathways explaining the relationship between caregiver social support and child psychosocial wellbeing with similar populations, and quantitatively investigate direct and indirect effects of potential mediating factors. Findings speak both to the importance of psychosocial support for parenting interventions and the potential to strengthen child-focused interventions through the broader family social network. PMID- 26357923 TI - Heat protection behaviour in the UK: results of an online survey after the 2013 heatwave. AB - BACKGROUND: The Heatwave Plan for England provides guidance for personal and home protection measures during heatwaves. Although studies in the USA, Australia and Europe have surveyed heat-related behaviours during heatwaves, few have been conducted in the UK. This study assesses personal and housing (at-home) behaviour and housing characteristics of the UK population during the 2013 heatwave. METHODS: This paper analyses data from 1497 respondents of an online survey on heat protection measures and behaviour. Participants were asked questions about their behaviour during the 2013 heatwave, the characteristics of their current housing as well as about any negative health outcomes experienced due to the hot weather. We used multinomial logit regression to analyse personal and home heat protection behaviour and logistic regression to analyse characteristics of participants' current home (installed air conditioner, curtains etc.). We stratified the outcomes by age, sex, ethnicity, income, education and regional location. RESULTS: In 2013, for all heat-related illness (except tiredness), a higher proportion of those in the younger age groups reported symptoms compared with those in the older age groups. Women, higher income groups and those with higher education levels were found to be more likely to report always/often taking personal heat protective measures. The elderly were less likely to take some personal and home protective measures but were more likely to live in insulated homes and open windows at night to keep their home cool. CONCLUSION: Our study has found a high level of awareness of the actions to take during heatwaves in the UK, and has identified important demographic indicators of sections of the UK population that might benefit from additional or more targeted information. The health agencies should attempt to provide better information about heatwaves to those vulnerable (elderly, those at risk living in London, low income earners) or identify any barriers that might be preventing them from undertaking protective behaviour. PMID- 26357924 TI - The complete mitochondrial genomes of the Galapagos iguanas, Amblyrhynchus cristatus and Conolophus subcristatus. AB - The Galapagos iguanas are among the oldest vertebrate lineages on the Galapagos archipelago, and the evolutionary history of this clade is of great interest to biologists. We describe here the complete mitochondrial genomes of the marine iguana, Amblyrhynchus cristatus (Genbank accession number: KT277937) and the land iguana Conolophus subcristatus (Genbank accession number: KT277936). The genomes contain 13 protein-coding genes, 22 transfer RNAs, and two ribosomal RNAs genes, as well as a control region (CR). Both species have an identical gene order, which matches that of Iguana iguana. The CR of both Galapagos iguanas features similar tandem repeats units, which are absent in I. iguana. We present a phylogeny of the Iguanidae based on complete mitochondrial genomes, which confirms the sister-group relationship of Galapagos iguanas. These new mitochondrial genomes constitute an important data source for future exploration of the phylogenetic relationships and evolutionary history of the Galapagos iguanas. PMID- 26357926 TI - Biomechanical analysis of the snatch technique in junior elite female weightlifters. AB - The strength and technical competence of junior female lifters play a decisive role not only for their current but also adulthood performance. The objective of this study was to investigate the three-dimensional kinematics of the snatch technique in junior female weightlifters. Ten elite junior female weightlifters participated in the study. Two cameras operating at 50 fields per second were used to record the lifts. The heaviest successful lifts were selected for the kinematic analysis. The kinematical data were obtained using a motion analysis system. The duration of the first pull was significantly longer than that of the other phases (P < 0.05). Maximum extension angle and velocity of the lower limb joints were significantly greater in the second pull (P < 0.05). The greatest extension angle was found in the knee joint during the first pull, while the greatest extension angle was observed in the hip joint during the second pull (P < 0.05). Maximum extension velocity of the knee and hip joints was significantly greater than that of the ankle in both phases (P < 0.05). In addition, the vertical velocity of the barbell and the absolute and relative power outputs was significantly higher in the second pull than in the first pull (P < 0.05). In the snatch lifting of junior female weightlifters, the angular kinematics of lower limb joints, the linear kinematics and trajectory of the barbell and other energy characteristics are similar to and consistent with the values reported in literature for adult female weightlifters. PMID- 26357927 TI - Women's position and attitudes towards female genital mutilation in Egypt: A secondary analysis of the Egypt demographic and health surveys, 1995-2014. AB - BACKGROUND: Female genital mutilation (FGM) is still widespread in Egyptian society. It is strongly entrenched in local tradition and culture and has a strong link to the position of women. To eradicate the practice a major attitudinal change is a required for which an improvement in the social position of women is a prerequisite. This study examines the relationship between Egyptian women's social positions and their attitudes towards FGM, and investigates whether the spread of anti-FGM attitudes is related to the observed improvements in the position of women over time. METHODS: Changes in attitudes towards FGM are tracked using data from the Egypt Demographic and Health Surveys from 1995 to 2014. Multilevel logistic regressions are used to estimate 1) the effects of indicators of a woman's social position on her attitude towards FGM, and 2) whether these effects change over time. RESULTS: Literate, better educated and employed women are more likely to oppose FGM. Initially growing opposition to FGM was related to the expansion of women's education, but lately opposition to FGM also seems to have spread to other segments of Egyptian society. CONCLUSIONS: The improvement of women's social position has certainly contributed to the spread of anti-FGM attitudes in Egyptian society. Better educated and less traditional women were at the heart of this change, and formed the basis from where anti-FGM sentiment has spread over wider segments of Egyptian society. PMID- 26357925 TI - Correlation analysis of the transcriptome of growing leaves with mature leaf parameters in a maize RIL population. AB - BACKGROUND: To sustain the global requirements for food and renewable resources, unraveling the molecular networks underlying plant growth is becoming pivotal. Although several approaches to identify genes and networks involved in final organ size have been proven successful, our understanding remains fragmentary. RESULTS: Here, we assessed variation in 103 lines of the Zea mays B73xH99 RIL population for a set of final leaf size and whole shoot traits at the seedling stage, complemented with measurements capturing growth dynamics, and cellular measurements. Most traits correlated well with the size of the division zone, implying that the molecular basis of final leaf size is already defined in dividing cells of growing leaves. Therefore, we searched for association between the transcriptional variation in dividing cells of the growing leaf and final leaf size and seedling biomass, allowing us to identify genes and processes correlated with the specific traits. A number of these genes have a known function in leaf development. Additionally, we illustrated that two independent mechanisms contribute to final leaf size, maximal growth rate and the duration of growth. CONCLUSIONS: Untangling complex traits such as leaf size by applying in depth phenotyping allows us to define the relative contributions of the components and their mutual associations, facilitating dissection of the biological processes and regulatory networks underneath. PMID- 26357929 TI - Risk of selection bias in randomised trials. AB - BACKGROUND: Selection bias occurs when recruiters selectively enrol patients into the trial based on what the next treatment allocation is likely to be. This can occur even if appropriate allocation concealment is used if recruiters can guess the next treatment assignment with some degree of accuracy. This typically occurs in unblinded trials when restricted randomisation is implemented to force the number of patients in each arm or within each centre to be the same. Several methods to reduce the risk of selection bias have been suggested; however, it is unclear how often these techniques are used in practice. METHODS: We performed a review of published trials which were not blinded to assess whether they utilised methods for reducing the risk of selection bias. We assessed the following techniques: (a) blinding of recruiters; (b) use of simple randomisation; (c) avoidance of stratification by site when restricted randomisation is used; (d) avoidance of permuted blocks if stratification by site is used; and (e) incorporation of prognostic covariates into the randomisation procedure when restricted randomisation is used. We included parallel group, individually randomised phase III trials published in four general medical journals (BMJ, Journal of the American Medical Association, The Lancet, and New England Journal of Medicine) in 2010. RESULTS: We identified 152 eligible trials. Most trials (98%) provided no information on whether recruiters were blind to previous treatment allocations. Only 3% of trials used simple randomisation; 63% used some form of restricted randomisation, and 35% did not state the method of randomisation. Overall, 44% of trials were stratified by site of recruitment; 27% were not, and 29% did not report this information. Most trials that did stratify by site of recruitment used permuted blocks (58%), and only 15% reported using random block sizes. Many trials that used restricted randomisation also included prognostic covariates in the randomisation procedure (56%). CONCLUSIONS: The risk of selection bias could not be ascertained for most trials due to poor reporting. Many trials which did provide details on the randomisation procedure were at risk of selection bias due to a poorly chosen randomisation methods. Techniques to reduce the risk of selection bias should be more widely implemented. PMID- 26357928 TI - A comparison of CPAP and CPAPFLEX in the treatment of obstructive sleep apnea in World Trade Center responders: study protocol for a randomized controlled trial. AB - BACKGROUND: Following the World Trade Center disaster, a large number of individuals involved in rescue and recovery activity were exposed to significant amounts of dust, and reported symptoms of chronic nasal and sinus inflammation. An unusually high prevalence of obstructive sleep apnea (OSA) has also been observed in this World Trade Center Responder population. This project aims to examine the relationship between nasal pathology and OSA. Our hypothesis is that increased nasal resistance due to nasal inflammation predisposes to OSA in this population. Continuous Positive Airway Pressure (CPAP) is the standard therapy for OSA but despite its efficacy has poor adherence. Subjects with high nasal resistance may have greater difficulty in tolerating this therapy than those who do not have high nasal resistance. Reduction of excess expiratory positive pressure by the modality known as Cflex(TM) during Continuous Positive Airway Pressure therapy (CPAP(Flex)) has been suggested to improve comfort without compromising efficacy. We will compare CPAP to CPAP(Flex) in subjects with OSA. STUDY DESIGN: Subjects with new onset habitual snoring will be screened for OSA using home sleep studies and rhinomanometry will be used to determine nasal resistance. In 400 subjects with OSA we will perform a randomized double blind cross-over study comparing CPAP to CPAP(flex), and relate nasal resistance to adherence to CPAP therapy. DISCUSSION: This is the first multicenter trial designed to test the hypothesis that adherence to CPAP therapy relates to nasal resistance and CPAP(Flex) will improve adherence to CPAP in those subjects with high nasal resistance. We anticipate the following results from this trial: 1. Increased nasal resistance is associated with decreased adherence to CPAP therapy. 2. Use of CPAP(Flex) improves adherence with CPAP therapy in subjects with high nasal resistance, but not in those with low nasal resistance. 3. The benefit of CPAP(Flex) on adherence is greatest when offered at CPAP therapy initiation rather than as a "rescue" therapy in subjects with high nasal resistance. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01753999, Date: 12 December 2012. PMID- 26357922 TI - The Mammalian Blood-Testis Barrier: Its Biology and Regulation. AB - Spermatogenesis is the cellular process by which spermatogonia develop into mature spermatids within seminiferous tubules, the functional unit of the mammalian testis, under the structural and nutritional support of Sertoli cells and the precise regulation of endocrine factors. As germ cells develop, they traverse the seminiferous epithelium, a process that involves restructuring of Sertoli-germ cell junctions, as well as Sertoli-Sertoli cell junctions at the blood-testis barrier. The blood-testis barrier, one of the tightest tissue barriers in the mammalian body, divides the seminiferous epithelium into 2 compartments, basal and adluminal. The blood-testis barrier is different from most other tissue barriers in that it is not only comprised of tight junctions. Instead, tight junctions coexist and cofunction with ectoplasmic specializations, desmosomes, and gap junctions to create a unique microenvironment for the completion of meiosis and the subsequent development of spermatids into spermatozoa via spermiogenesis. Studies from the past decade or so have identified the key structural, scaffolding, and signaling proteins of the blood testis barrier. More recent studies have defined the regulatory mechanisms that underlie blood-testis barrier function. We review here the biology and regulation of the mammalian blood-testis barrier and highlight research areas that should be expanded in future studies. PMID- 26357930 TI - Hearing impairment after childhood bacterial meningitis dependent on etiology in Luanda, Angola. AB - OBJECTIVE: Childhood bacterial meningitis (BM) damages hearing, but the potential of different agents to cause impairment in developing countries is poorly understood. We compared the extent of hearing impairment in BM caused by Haemophilus influenzae type b (Hib), Streptococcus pneumoniae or Neisseria meningitidis among children aged 2 months to 13 years in Luanda, Angola. METHODS: Hearing of 685 ears of 351 (78%) survivors among 723 enrolled patients was tested by brainstem-evoked response audiometry on day 7 of hospitalization. The causative agent was sought by cerebrospinal fluid culture, PCR or the latex agglutination test. RESULTS: Altogether, 45 (12%) of the survivors were deaf (threshold >80 dB), and 20 (6%) had a threshold of 80 dB. The incidence of any kind of hearing loss, with >=60 dB, was 34% with Hib, 30% with S. pneumoniae, 19% with N. meningitidis and 33% with other bacteria. Examining all ears combined and using the >=60 dB threshold, the agents showed dissimilar harm (P=0.005), Hib being the most frequent and N. meningitidis the most infrequent cause. Compared to other agents, S. pneumoniae more often caused deafness (P=0.025) and hearing impairment at >=60 dB (P=0.017) in infants, whereas this level of hearing loss in older survivors was most commonly caused by Hib (P=0.031). CONCLUSIONS: BM among children in Angola is often followed by hearing impairment, but the risk depends on the agent. S. pneumoniae is a major problem among infants, whereas Hib is mainly a risk beyond 12 months. N. meningitidis impairs hearing less frequently. PMID- 26357931 TI - Risk factors for surgical site infection and delayed wound healing after orthopedic surgery in rheumatoid arthritis patients. AB - OBJECTIVE: To investigate the prevalence and the risk factors of surgical-site infection (SSI) and delayed wound healing (DWH) in patients with rheumatoid arthritis (RA) underwent orthopedic surgery. METHODS: We reviewed the records of 1036 elective orthopedic procedures undertaken in RA patients. Risk factors for SSI and DWH were assessed by logistic regression analysis using age, body mass index, disease duration, pre-operative laboratory data, surgical procedure, corticosteroid use, co-morbidity, and use of conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) and biological DMARDs (bDMARDs) as variables. RESULTS: SSI and DWH were identified in 19 cases and 15 cases, respectively. One case of SSI and three cases of DWH were recorded among 196 procedures in patients using bDMARDs. Foot and ankle surgery was associated with an increased risk of SSI (odds ratio (OR), 3.167; 95% confidence interval (CI), 1.256-7.986; p = 0.015). Total knee arthroplasty (TKA; OR, 4.044; 95% CI, 1.436 11.389; p = 0.008) and disease duration (OR, 1.004; 95% CI, 1.000-1.007; p = 0.029) were associated with an increased risk of DWH. CONCLUSIONS: Our results indicated foot and ankle surgery, and TKA and disease duration as risk factors for SSI and DWH, respectively. bDMARDs was not associated with an increased risk of SSI and DWH. PMID- 26357932 TI - Management of post-dural puncture headache in late pregnancy before the onset of labour. PMID- 26357933 TI - Changes in pleth variability index and detection of hypotension during spinal anaesthesia for caesarean section. PMID- 26357934 TI - Postural change from lateral to supine is an important mechanism enhancing cephalic spread after injection of intrathecal 0.5% plain bupivacaine for cesarean section. AB - BACKGROUND: Spinal anesthesia is widely used for cesarean section, but the factors that affect the spread of the block in pregnant patients are still not fully explained. This study was designed to investigate the effect of postural changes on sensory block level. METHODS: Thirty patients scheduled for elective cesarean section under combined spinal-epidural anesthesia were randomly allocated into three groups. After intrathecal injection of 0.5% plain bupivacaine 7.5mg, patients in group S were immediately placed in the supine position with left tilt, patients in group L5 were kept lateral for 5 min and then turned to the supine position with left tilt, and patients in group L10 were kept lateral for 10 min and then turned to the supine position with left tilt. RESULTS: At 5 min, median cephalad level of sensory block was lower in groups L5 and L10 compared with group S (corrected P<0.001); at 10 min, median cephalad sensory block level was lower in group L10 compared with group S (corrected P<0.001) and group L5 (corrected P<0.001), and lower in group L5 compared with group S (corrected P=0.033); at 15 min, median cephalad level of sensory block was lower in group L10 compared with group S (corrected P=0.003) and group L5 (corrected P=0.015). CONCLUSIONS: In our population, using 0.5% plain bupivacaine 7.5mg, postural change from the lateral position to the supine position is an important mechanism enhancing cephalic spread of spinal anesthesia during late pregnancy. PMID- 26357935 TI - Influence of structural anisotropy on mesogenity of Eu(III) adducts and optical properties of vitrified films formed on their base. AB - A new series of europium adducts with the general formula Eu(CPDk3-CnH2n+1)3Phen, where CPDk3-CnH2n+1 denotes beta-diketones and Phen is 1,10-phenanthroline, was synthesized. The obtained mesogenic complexes were heated to the temperatures of the isotropic liquid state and then cooled. The complexes having short CH3 and C2H5 substituents crystallized upon cooling, and the complexes with longer substituents from C3H7 to C6H13 underwent a glass transition with the formation of optically transparent amorphous films. Inside the series the complexes with C7H15 and C8H17 substituents exhibited a unusual smectic C mesomorphism for lanthanidomesogens. On the basis of quantum-chemical simulations and the results of small-angle X-ray scattering the dependence between the anisotropy of Eu(III) complexes with various ligand environments and their supramolecular organization was found. The synthesized Eu(III) complexes in the solid state show intense red photoluminescence upon irradiation by ultraviolet light (lambdamax - 337 nm). PMID- 26357936 TI - Zwitterionic Nanofibers of Super-Glue for Transparent and Biocompatible Multi Purpose Coatings. AB - Here we show that macrozwitterions of poly(ethyl 2-cyanoacrylate), commonly called Super Glue, can easily assemble into long and well defined fibers by electrospinning. The resulting fibrous networks are thermally treated on glass in order to create transparent coatings whose superficial morphology recalls the organization of the initial electrospun mats. These textured coatings are characterized by low liquid adhesion and anti-staining performance. Furthermore, the low friction coefficient and excellent scratch resistance make them attractive as solid lubricants. The inherent texture of the coatings positively affects their biocompatibility. In fact, they are able to promote the proliferation and differentiation of myoblast stem cells. Optically-transparent and biocompatible coatings that simultaneously possess characteristics of low water contact angle hysteresis, low friction and mechanical robustness can find application in a wide range of technological sectors, from the construction and automotive industries to electronic and biomedical devices. PMID- 26357937 TI - [Management of deep-vein thrombosis: A 2015 update]. AB - Deep vein thrombosis (DVT) is a frequent and multifactor disease, with two major complications, post thrombotic syndrome and pulmonary embolism. Both transient (surgery, plaster immobilization, bed rest/hospitalization) and chronic/persistent (age, cancer, clinical or biological thrombophilia...) risk factors modulate treatment duration. Diagnostic management relies on clinical evaluations, probability followed by laboratory tests or imaging. So far, compression ultrasound is the diagnostic test of choice to make a positive diagnosis of DVT. Anticoagulants at therapeutic dose for at least 3 months constitute the cornerstones of proximal (i.e. involving popliteal or more proximal veins) DVT therapeutic management. The arrival of new oral anticoagulants should optimize ambulatory management of DVT. PMID- 26357938 TI - [Femoral artery pseudoaneurysms encountered in orthopedics and traumatology]. AB - BACKGROUND AND PURPOSE: Most published articles regarding orthopedic- and trauma related femoral artery pseudoaneurysms (FAPs) are case reports in English. Reported cases are often associated with a literature review but actually provide little robust data. We wanted to summarize the current knowledge on diagnostic and therapeutic features of these FAPs. METHODS: A new case of superficial FAP is described followed by a review of the literature. A bibliographic search was performed online (PubMed, ScinceDirect) from 1964 to 2015 using the descriptors "traumatic femoral pseudoaneurysm, orthopedic surgery, osteochondroma". RESULTS: A total of 64 cases of FAPs was analyzed. There were 50 men with an average age of 40.72+/-26.45 years old. The most common clinical presentation was painful swelling (34%). Arteriography was the commonest radiological investigation used (63%). The main etiologies were orthopedic injuries (47%), surgery of the upper thigh (30%) and femoral osteochondromas (23%). Arterial injuries included superficial femoral (47%) and profunda femoris artery (50%). The treatment was open surgery (56%) or endovascular repair (36%). Deep femoral artery and its branches were embolized (47%) or ligated (38%). Endovascular stenting was performed in 30% of posttraumatic FAPs. All FAPs relating to osteochondromas were repaired surgically. Postoperative courses were uneventful in 95% of patients. CONCLUSION: Endovascular embolization is preferred in management of postsurgical FAPs which have usually involved the deep femoral artery. Endovascular stenting graft may be proposed for posttraumatic FAPs, for which the superficial femoral trunk is the most often involved vessel. Surgical repair should be performed when endovascular stenting graft is not feasible. Surgical repair is mandatory for all FAPs secondary to traumatic exostoses. PMID- 26357939 TI - Mechanosensitive activation of CFTR by increased cell volume and hydrostatic pressure but not shear stress. AB - The cystic fibrosis transmembrane conductance regulator (CFTR) is a Cl(-) channel that is essential for electrolyte and fluid homeostasis. Preliminary evidence indicates that CFTR is a mechanosensitive channel. In lung epithelia, CFTR is exposed to different mechanical forces such as shear stress (Ss) and membrane distention. The present study questioned whether Ss and/or stretch influence CFTR activity (wild type, ?F508, G551D). Human CFTR (hCFTR) was heterologously expressed in Xenopus oocytes and the response to the mechanical stimulus and forskolin/IBMX (FI) was measured by two-electrode voltage-clamp experiments. Ss had no influence on hCFTR activity. Injection of an intracellular analogous solution to increase cell volume alone did not affect hCFTR activity. However, hCFTR activity was augmented by injection after pre-stimulation with FI. The response to injection was similar in channels carrying the common mutations ?F508 and G551D compared to wild type hCFTR. Stretch-induced CFTR activation was further assessed in Ussing chamber measurements using Xenopus lung preparations. Under control conditions increased hydrostatic pressure (HP) decreased the measured ion current including activation of a Cl(-) secretion that was unmasked by the CFTR inhibitor GlyH-101. These data demonstrate activation of CFTR in vitro and in a native pulmonary epithelium in response to mechanical stress. Mechanosensitive regulation of CFTR is highly relevant for pulmonary physiology that relies on ion transport processes facilitated by pulmonary epithelial cells. PMID- 26357940 TI - Safety, tolerability and pharmacokinetics of AFN-1252 administered as immediate release tablets in healthy subjects. AB - AIMS: AFN-1252 is a novel inhibitor of FabI, an essential enzyme in Staphylococcus spp. This study was undertaken to assess the safety, tolerability and pharmacokinetic properties of AFN-1252, following oral administration in an ascending dose trial. MATERIALS & METHODS: This was a double-blind, randomized, placebo-controlled, two-part study. In Part I, single doses (QD) of 100, 200, 300, or 400 mg AFN-1252 were administered. In Part II, subjects received 200, 400, 600, or 800 mg (total daily dose) where 100, 200 and 400-mg doses were given twice in one day. RESULTS: AFN-1252 was well-absorbed with Cmax at 3-4 h when given once per day and 2.5-9 h when dosed twice in a single dosing day. T1/2 ranged from 8 to 11 h. Total and peak exposures of AFN-1252 increased nonlinearly. Adverse events were primarily mild and resolved promptly. CONCLUSIONS: Oral doses of AFN-1252 were safe and well tolerated. AFN-1252 has the potential for once or twice-a-day dosing for treatment of staphylococcal infections. PMID- 26357941 TI - Metal nanodot arrays fabricated via seed-mediated electroless plating with block copolymer thin film scaffolding. AB - We present an alternative approach to fabricating hexagonally arranged nanodot arrays of various metals by seed-mediated electroless plating with a cylinder forming block copolymer thin film, PEO-b-PMA(Az), as a scaffold. Metal ions were selectively incorporated into PEO cylinders, followed by their reduction to metal and the etching of the scaffold to obtain highly ordered seed arrays of Au, Pd, and Pt. Nanodot arrays of the target metals (Au, Ag, and Ni) were selectively grown on the seed with their highly ordered arrangement by electroless plating. We studied the fabrication processes' suitability for control of the nanodot array size, as well as the plasmonic properties thereof. PMID- 26357942 TI - The use of bisphosphonates in women: when to use and when to stop. AB - INTRODUCTION: Bisphosphonates (BPs) are the most commonly used drugs in osteoporosis. AREAS COVERED: This review focuses on the criteria for identifying patients who should be treated with BPs and also the rational for the duration of treatment. EXPERT OPINION: BPs remain the mainstay for the treatment of osteoporosis. For their low cost, the treatment threshold is related exclusively to the ratio between expected benefits and the risk of side effects. This is the case of patients with prior fragility fracture or with low bone density and the presence of other relevant risk factors. The treatment should continue for 3 - 5 years or until fracture risk is no longer high. Afterward a treatment holiday should be considered on the light of the increasing risk of side effects but its duration is still controversial. The duration of this treatment holiday depends on the drug used. Discontinuation of risedronate and ibandronate is associated with the quick loss of the acquired benefits and with these two BPs discontinuation should not exceed 6 months. Alendronate and zoledronate are characterized by a persistent effect after discontinuing treatment and this would allow a more prolonged drug holiday. PMID- 26357943 TI - Using mobile technology to deliver a cognitive behaviour therapy-informed intervention in early psychosis (Actissist): study protocol for a randomised controlled trial. AB - BACKGROUND: Cognitive behaviour therapy (CBT) is recommended for the treatment of psychosis; however, only a small proportion of service users have access to this intervention. Smartphone technology using software applications (apps) could increase access to psychological approaches for psychosis. This paper reports the protocol development for a clinical trial of smartphone-based CBT. METHODS/DESIGN: We present a study protocol that describes a single-blind randomised controlled trial comparing a cognitive behaviour therapy-informed software application (Actissist) plus Treatment As Usual (TAU) with a symptom monitoring software application (ClinTouch) plus TAU in early psychosis. The study consists of a 12-week intervention period. We aim to recruit and randomly assign 36 participants registered with early intervention services (EIS) across the North West of England, UK in a 2:1 ratio to each arm of the trial. Our primary objective is to determine whether in people with early psychosis the Actissist app is feasible to deliver and acceptable to use. Secondary aims are to determine whether Actissist impacts on predictors of first episode psychosis (FEP) relapse and enhances user empowerment, functioning and quality of life. Assessments will take place at baseline, 12 weeks (post-treatment) and 22-weeks (10 weeks post-treatment) by assessors blind to treatment condition. The trial will report on the feasibility and acceptability of Actissist and compare outcomes between the randomised arms. The study also incorporates semi-structured interviews about the experience of participating in the Actissist trial that will be qualitatively analysed to inform future developments of the Actissist protocol and app. DISCUSSION: To our knowledge, this is the first controlled trial to test the feasibility, acceptability, uptake, attrition and potential efficacy of a CBT informed smartphone app for early psychosis. Mobile applications designed to deliver a psychologically-informed intervention offer new possibilities to extend the reach of traditional mental health service delivery across a range of serious mental health problems and provide choice about available care. TRIAL REGISTRATION: ISRCTN34966555. Date of first registration: 12 June 2014. PMID- 26357944 TI - Efficacy and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in patients with moderate-to-severe plaque psoriasis over 52 weeks: a phase III, randomized controlled trial (ESTEEM 2). AB - BACKGROUND: Apremilast, an oral phosphodiesterase 4 inhibitor, regulates immune responses associated with psoriasis. OBJECTIVES: ESTEEM 2 evaluated the efficacy and safety of apremilast 30 mg twice daily for moderate-to-severe plaque psoriasis. METHODS: This phase III, double-blind, placebo-controlled trial randomized adults to apremilast or placebo (2 : 1). At week 16, placebo patients switched to apremilast. At week 32, apremilast patients achieving >= 50% reduction in Psoriasis Area and Severity Index (PASI 50) were rerandomized (1 : 1) to continue apremilast or receive placebo. Upon loss of 50% of PASI improvement obtained at week 32, patients rerandomized to placebo resumed apremilast. RESULTS: The modified intention-to-treat population (full analysis set) included 137 placebo and 274 apremilast patients. At week 16, significantly more apremilast patients achieved PASI 75 (28.8%), PASI 50 (55.5%) and static Physician's Global Assessment score of 0 or 1 (20.4%) vs. placebo (5.8%, 19.7%, 4.4%, respectively; P < 0.001). Most patients rerandomized to apremilast at week 32 had a PASI 50 response at week 52 (80%). Patients treated with apremilast showed significant improvements in quality of life (as assessed by the Dermatology Life Quality Index) and pruritus at week 16 compared with placebo (P < 0.001). The exposure-adjusted incidence of adverse events did not increase with continued apremilast treatment for up to 52 weeks. The most common adverse events were nausea, diarrhoea, nasopharyngitis and upper respiratory tract infection. CONCLUSIONS: Apremilast was effective in the treatment of moderate-to-severe plaque psoriasis over 52 weeks. PMID- 26357945 TI - Rapid Control of T3 Thyrotoxicosis in Patients with Metastatic Follicular Thyroid Cancer Treated with Lenvatinib. PMID- 26357946 TI - The Canadian Management of Bovine Spongiform Encephalopathy in Historical and Scientific Perspective, 1990-2014. AB - On February 11, 2015, the Canadian Food Inspection Agency announced that a cow born and raised in Alberta had tested positive for bovine spongiform encephalopathy (BSE), commonly known as mad cow disease. BSE is a prion disease of cattle that, when transmitted to humans, produces a fatal neurodegenerative disease known as variant Creutzfeldt-Jakob disease. We believe that this latest case of BSE in Canadian cattle suggests the timeliness of a review of the management of BSE in Canada from a historically and scientifically informed perspective. In this article, we ask: how did the Canadian management of BSE between 1990 and 2014 engage with the contemporary understanding of BSE's human health implications? We propose that Canadian policies largely ignored the implicit medical nature of BSE, treating it as a purely agricultural and veterinary issue. In this way, policies to protect Canadians were often delayed and incomplete, in a manner disturbingly reminiscent of Britain's failed management of BSE. Despite assurances to the contrary, it is premature to conclude that BSE (and with it the risk of variant Creutzfeldt-Jakob disease) is a thing of Canada's past: BSE remains very much an issue in Canada's present. PMID- 26357947 TI - Tumor Microenvironment Versus Cancer Stem Cells in Cholangiocarcinoma: Synergistic Effects? AB - Cholangiocarcinoma (CCAs) may be defined as tumors that derived from the biliary tree with the differentiation in the biliary epithelial cells. This tumor is malignant, extremely aggressive with a poor prognosis. It can be treated surgically and its pathogenesis is poorly understood. The tumor microenvironment (TME) is a very important factor in the regulation of tumor angiogenesis, invasion, and metastasis. Besides cancer stem cells (CSCs) can modulate tumor growth, stroma formation, and migratory capability. The initial stage of tumorigenesis is characterized by genetic mutations and epigenetic alterations due to intrinsic factors which lead to the generation of oncogenes thus inducing tumorigenesis. CSCs may result from precancerous stem cells, cell de differentiation, normal stem cells, or an epithelial-mesenchymal transition (EMT). CSCs have been found in the cancer niche, and EMT may occur early within the tumor microenvironment. Previous studies have demonstrated evidence of cholangiocarcinoma stem cells (CD133, CD24, EpCAM, CD44, and others) and the presence of these markers has been associated with malignant potential. The interaction between TME and cholangiocarcinoma stem cells via signaling mediators may create an environment that accommodates tumor growth, yielding resistance to cytotoxic insults (chemotherarapeutic). While progress has been made in the understanding of the mechanisms, the interactions in the tumorigenic process still remain a major challenge. Our review, addresses recent concepts of TME-CSCs interaction and will emphasize the importance of early detection with the use of novel diagnostic mechanisms such as CCA-CSC biomarkers and the importance of tumor stroma to define new treatments. J. Cell. Physiol. 231: 768-776, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26357948 TI - Overcoming language barriers in healthcare: A protocol for investigating safe and effective communication when patients or clinicians use a second language. AB - BACKGROUND: Miscommunication in the healthcare sector can be life-threatening. The rising number of migrant patients and foreign-trained staff means that communication errors between a healthcare practitioner and patient when one or both are speaking a second language are increasingly likely. However, there is limited research that addresses this issue systematically. This protocol outlines a hospital-based study examining interactions between healthcare practitioners and their patients who either share or do not share a first language. Of particular interest are the nature and efficacy of communication in language discordant conversations, and the degree to which risk is communicated. Our aim is to understand language barriers and miscommunication that may occur in healthcare settings between patients and healthcare practitioners, especially where at least one of the speakers is using a second (weaker) language. METHODS/DESIGN: Eighty individual interactions between patients and practitioners who speak either English or Chinese (Mandarin or Cantonese) as their first language will be video recorded in a range of in- and out-patient departments at three hospitals in the Metro South area of Brisbane, Australia. All participants will complete a language background questionnaire. Patients will also complete a short survey rating the effectiveness of the interaction. Recordings will be transcribed and submitted to both quantitative and qualitative analyses to determine elements of the language used that might be particularly problematic and the extent to which language concordance and discordance impacts on the quality of the patient-practitioner consultation. DISCUSSION: Understanding the role that language plays in creating barriers to healthcare is critical for healthcare systems that are experiencing an increasing range of culturally and linguistically diverse populations both amongst patients and practitioners. The data resulting from this study will inform policy and practical solutions for communication training, provide an agenda for future research, and extend theory in health communication. PMID- 26357949 TI - The Epidemiology of Anaphylaxis. AB - Anaphylaxis is a dramatic expression of systemic allergy. The lifetime prevalence of anaphylaxis is currently estimated at 0.05-2 % in the USA and ~3 % in Europe. Several population-specific studies have noted a rise in the incidence, particularly in the hospitalizations and ER visits due to anaphylaxis. The variable signs and symptoms that constitute the diagnostic criteria for anaphylaxis, the differences in diagnostic algorithms, and the limitations in the current coding systems have made summarizing epidemiologic data and comparing study results challenging. Nevertheless, across all studies, the most common triggers continue to be medications, food, and venom. Various risk factors for more severe reactions generally include older age, history of asthma, and having more comorbid diseases. Interesting seasonal, geographic, and latitude differences have been observed in anaphylaxis prevalence and incidence rates, suggesting a possible role of vitamin D and sun exposure in modifying anaphylaxis risk. While the incidence and prevalence of anaphylaxis appear to be increasing in certain populations, the overall fatality rate remains relatively low. PMID- 26357950 TI - Possible participation of IgG4 in the activation of complement in IgG4-related disease with hypocomplementemia. AB - OBJECTIVE: To investigate which IgG subclasses contribute to the activation of the complement pathway in IgG4-related disease (IgG4RD) patients with hypocomplementemia. METHODS: Sera of IgG4RD patients were analyzed for the binding ability of IgG subclasses to complement component 1q (C1q). Polyethylene glycol (PEG) precipitates containing immune complexes (ICs) in sera of IgG4RD patients were analyzed for IgG subclass composition by Western blotting. PEG precipitates containing ICs (PEG-ICs) in sera of patients were also analyzed for their ability to consume complement in normal human serum (NHS) using a total complement hemolytic (CH50) assay and a commercial kit to measure the complement capacity of all three individual complement pathways. RESULTS: The C1q binding assay revealed high serum levels of C1q-binding IgG4 in IgG4RD patients with hypocomplementemia. ICs in PEG precipitates were formed with IgG4 in IgG4RD patients, regardless of the presence or absence of hypocomplementemia. We observed a marked reduction of CH50 and reduced complement activity in the classical complement pathway as well as the mannan-binding lectin complement pathway in NHS incubated with PEG-IC isolated from IgG4RD patients with hypocomplementemia. CONCLUSION: Our results suggest that IgG4 may participate in the activation of complement in IgG4RD patients with hypocomplementemia. PMID- 26357951 TI - Cerebral Area Differential Redox Response of Neonatal Rats to Selenite-Induced Oxidative Stress and to Concurrent Administration of Highbush Blueberry Leaf Polyphenols. AB - Our goal was to delineate the mechanisms of selenite-induced oxidative stress in neonatal rats and investigate the potential of blueberry leaf polyphenols to counteract the induced stress. Vaccinium corymbosum leaf decoction (BLD) was analyzed by UPLC-MS and LC-DAD, along with its in vitro antioxidant activity (DPPH radical scavenging, FRAP, ferrous chelation). Newborn suckling Wistar rats were randomly divided into three groups: 'Se' and 'SeBLD' received 20 MUmol Na2SeO3/kg BW subcutaneously (PN day 10); 'SeBLD' received 100 mg dry BLD/kg BW intraperitoneally (PN11 and 12) and Group 'C' received normal saline. Betaiochemical analysis revealed tissue-specific effects of selenite. Brain as a whole was more resistant to selenite toxicity in comparison to liver; midbrain and cerebellum were in general not affected, but cortex was moderately disturbed. Liver lipid peroxidation, GSH, SOD, CAT, GPx were significantly affected, whereas proteolytic activity was not. BLD, which is rich in chlorogenic acid and flavonols (especially quercetin derivatives), exerted significant antioxidant protective effects in all regions. In conclusion, we provide for the first time an insight to the neonatal rat cerebral and liver redox response against a toxic selenite dose and blueberry leaf polyphenols. PMID- 26357952 TI - Effect of price changes in little cigars and cigarettes on little cigar sales: USA, Q4 2011-Q4 2013. AB - INTRODUCTION: Little cigars are comparable to cigarettes in terms of shape, size, filters and packaging. Disproportionate tobacco excise taxes, which directly affect purchase price, may lead consumers to substitute cigarettes with less expensive little cigars. This study estimated the effects of little cigar and cigarette prices on little cigar sales. METHODS: Sales data from a customised retail scanner database were used to model a log-log equation to infer own-price and cross-price elasticity of demand for little cigars relative to little cigar and cigarette prices, respectively, from quarter 4 of 2011 to quarter 4 of 2013. Data were available for convenience stores (C-stores) (n=29 states); food, drug and mass merchandisers (FDMs) (n=44 states); and C-stores and FDMs combined (n=27 states). The dependent variable was per capita little cigar pack sales, and key independent variables were the price index for little cigars and cigarettes. RESULTS: A 10% increase in little cigar price was associated with a 25% (p<0.01) decrease in little cigar sales in C-stores alone, and a 31.7% (p<0.01) decrease in C-stores and FDMs combined. A 10% increase in cigarette price was associated with a 21.5% (p<0.05) increase in little cigar sales in C-stores, and a 27.3% (p<0.01) increase in C-stores and FDMs combined. CONCLUSIONS: Our results suggest that US cigarette smokers are avoiding the high cost of cigarettes by switching to lower priced little cigars. Increasing and equalising prices among comparable products, like cigarettes and little cigars, may motivate cost-conscious smokers to quit. PMID- 26357953 TI - [Lymph node and distant metastases of thyroid gland cancer. Metastases in the thyroid glands]. AB - The different biological features of the various major entities of thyroid cancer, e.g. papillary, follicular, poorly differentiated, anaplastic and medullary, depend to a large extent on their different metastatic spread. Papillary thyroid cancer (PTC) has a propensity for cervical lymphatic spread that occurs in 20-50 % of patients whereas distant metastasis occurs in < 5 % of cases. Cervical lymphadenopathy may be the first symptom particularly of (micro) PTC. In contrast follicular thyroid cancer (FTC) has a marked propensity for vascular but not lymphatic invasion and 10-20 % of FTC develop distant metastases. At the time of diagnosis approximately one third of medullary thyroid cancer (MTC) cases show lymph node metastases, in 10-15 % distant metastases and 25 % develop metastases during the course of the disease. Poorly differentiated (PDTC) and anaplastic thyroid cancer (ATC) spread via both lymphatic and vascular invasion. Thus distant metastases are relatively uncommon in DTC and when they occur, long-term stable disease is the typical clinical course. The major sites of distant metastases are the lungs and bone. Metastases to the brain, breasts, liver, kidneys, muscle and skin are relatively rare or even rare. The thyroid gland itself can be a site of metastases from a variety of other tumors. In autopsy series of patients with disseminated cancer disease, metastases to the thyroid gland were found in up to 10 % of cases. Metastases from other primary tumors to the thyroid gland have been reported in 1.4-3 % of patients who have surgery for suspected cancer of the thyroid gland. The most common primary cancers that metastasize to the thyroid gland are renal cell (48.1 %), colorectal (10.4 %), lung (8.3 %) and breast cancer (7.8 %) and surprisingly often sarcomas (4.0 %). PMID- 26357954 TI - Ultrastructural and immunocytochemical characterization of ameloblast-enamel adhesion at maturation stage in amelogenesis in Macaca fuscata tooth germ. AB - Maturation-stage ameloblasts are firmly bound to the tooth enamel by a basal lamina-like structure. The mechanism underlying this adhesion, however, remains to be fully clarified. The goal of this study was to investigate the mechanism underlying adhesion between the basal lamina-like structure and the enamel in monkey tooth germ. High-resolution immunogold labeling was performed to localize amelotin and laminin 332 at the interface between ameloblasts and tooth enamel. Minute, electron-dense strands were observed on the enamel side of the lamina densa, extending into the degrading enamel matrix to produce a well-developed fibrous layer (lamina fibroreticularis). In un-demineralized tissue sections, mineral crystals smaller than those in the bulk of the enamel were observed adhering to these strands where they protruded into the surface enamel. Immunogold particles reactive for amelotin were preferentially localized on these strands in the fibrous layer. On the other hand, those for laminin 332 were localized solely in the lamina densa; none were observed in the fibrous layer. These results suggest that the fibrous layer of the basal lamina-like structure is partly composed of amelotin molecules, and that these molecules facilitate ameloblast-enamel adhesion by promoting mineralization of the fibrous layer during the maturation stage of amelogenesis. PMID- 26357955 TI - A novel cell-stiffness-fingerprinting analysis by scanning atomic force microscopy: comparison of fibroblasts and diverse cancer cell lines. AB - Differing stimuli affect cell stiffness while cancer metastasis is associated with reduced cell stiffness. Cell stiffness determined by atomic force microscopy has been limited by measurement over nuclei to avoid spurious substratum effects in thin cytoplasmic domains, and we sought to develop a more complete approach including cytoplasmic areas. Ninety MUm square fields were recorded from ten separate sites of cultured human dermal fibroblasts (HDF) and three sites each for melanoma (MM39, WM175, and MeIRMu), osteosarcoma (SAOS-2 and U2OS), and ovarian carcinoma (COLO316 and PEO4) cell lines, each site providing 1024 measurements as 32 * 32 square grids. Stiffness recorded below 0.8 MUm height was occasionally influenced by substratum, so only stiffness recorded above 0.8 MUm was analysed, but all sites were included for height and volume analysis. COLO316 had the lowest cell height and volume, followed by HDF (p < 0.0001) and then PEO4, SAOS-2, MeIRMu, WM175, U2OS, and MM39. HDF were more stiff than all other cells (p < 0.0001), while in descending order of stiffness were PEO4, COLO316, WM175, SAOS-2, U2OS, MM39, and MeIRMu (p < 0.02). Stiffness fingerprints comprised scattergrams of stiffness values plotted against the height at which each stiffness value was recorded and appeared unique for each cell type studied, although in most cases the overall form of fingerprints was similar, with maximum stiffness at low height measurements and a second lower peak occurring at high height levels. We suggest that our stiffness-fingerprint analytical method provides a more nuanced description than previously reported and will facilitate study of the stiffness response to cell stimulation. PMID- 26357956 TI - Thermoelectric performance enhancement of calcium cobaltite through barium grain boundary segregation. AB - We report the dramatic increase of the Seebeck coefficient S and thermoelectric performance of calcium cobaltite Ca3Co4O9+delta ceramics through non stoichiometric addition of minute amount of Ba. The nominal chemistry of polycrystal pellets are Ca3BaxCo4O9+delta (x = 0, 0.01, 0.05, and 0.1). At 323 K, S of Ca3Co4O9+delta is 135 MUV K(-1), whereas S of Ba incorporated Ca3Ba0.05Co4O9+delta is 162.5 MUV.K(-1), which is the highest S value near room temperature regime reported for calcium cobaltite. The increase of S for Ca3Ba0.05Co4O9+delta sample is accompanied by the decrease of the electrical resistivity rho, resulting in high power factor S(2)/rho of 843 MUW.m(-1) K(-2) at 1007 K. Moreover, the thermal conductivities kappa of Ca3BaxCo4O9+delta decrease with the increase of the Ba addition. The figure-of-merit ZT for Ca3Ba0.05Co4O9+delta reaches 0.52 at 1073 K and a factor of 2.5 increment in comparison with undoped Ca3Co4O9+delta. Nanostructure examinations show that the added Ba segregated at the Ca3Co4O9+delta grain boundaries, while the Ca3Co4O9+delta grain interior is free of Ba. Performance enhancement is attributed to the carrier filtering effect caused by the Ba segregation. In addition, Ba segregation promotes the better crystal alignment and the development of crystal texture. PMID- 26357957 TI - Influenza B viruses: not to be discounted. AB - In contrast to influenza A viruses, which have been investigated extensively, influenza B viruses have attracted relatively little attention. However, influenza B viruses are an important cause of morbidity and mortality in the human population and full understanding of their biological and epidemiological properties is imperative to better control this important pathogen. However, some of its characteristics are still elusive and warrant investigation. Here, we review evolution, epidemiology, pathogenesis and immunity and identify gaps in our knowledge of influenza B viruses. The divergence of two antigenically distinct influenza B viruses is highlighted. The co-circulation of viruses of these two lineages necessitated the development of quadrivalent influenza vaccines, which is discussed in addition to possibilities to develop universal vaccination strategies. PMID- 26357958 TI - Socio-cultural and behavioural factors constraining latrine adoption in rural coastal Odisha: an exploratory qualitative study. AB - BACKGROUND: Open defecation is widely practiced in India. To improve sanitation and promote better health, the Government of India (GOI) has instituted large scale sanitation programmes supporting construction of public and institutional toilets and extending financial subsidies for poor families in rural areas for building individual household latrines. Nevertheless, many household latrines in rural India, built with government subsidies and the facilitation and support of non-government organizations (NGO), remain unused. Literature on social, cultural and behavioural aspects that constrain latrine adoption and use in rural India is limited. This paper examines defecation patterns of different groups of people in rural areas of Odisha state in India to identify causes and determinants of latrine non-use, with a special focus on government-subsidized latrine owners, and shortcomings in household sanitation infrastructure built with government subsidies. METHODS: An exploratory study using qualitative methods was conducted in rural communities in Odisha state. Methods used were focus group discussions (FGDs), and observations of latrines and interviews with their owners. FGDs were held with frontline NGO sanitation program staff, and with community members, separately by caste, gender, latrine type, and age group. Data were analysed using a thematic framework and approach. RESULTS: Government subsidized latrines were mostly found unfinished. Many counted as complete per government standards for disbursement of financial subsidies to contracted NGOs were not accepted by their owners and termed as 'incomplete'. These latrines lacked a roof, door, adequate walls and any provision for water supply in or near the cabin, whereas rural people had elaborate processes of cleansing with water post defecation, making presence of a nearby water source important. Habits, socialising, sanitation rituals and daily routines varying with caste, gender, marital status, age and lifestyle, also hindered the adoption of latrines. Interest in constructing latrines was observed among male heads for their female members especially a newlywed daughter-in-law, reflecting concerns for their privacy, security, and convenience. This paper elaborates on these different factors. CONCLUSIONS: Findings show that providing infrastructure does not ensure use when there are significant and culturally engrained behavioural barriers to using latrines. Future sanitation programmes in rural India need to focus on understanding and addressing these behavioural barriers. PMID- 26357959 TI - Effective Electrochemistry of Human Sulfite Oxidase Immobilized on Quantum-Dots Modified Indium Tin Oxide Electrode. AB - The bioelectrocatalytic sulfite oxidation by human sulfite oxidase (hSO) on indium tin oxide (ITO) is reported, which is facilitated by functionalizing of the electrode surface with polyethylenimine (PEI)-entrapped CdS nanoparticles and enzyme. hSO was assembled onto the electrode with a high surface loading of electroactive enzyme. In the presence of sulfite but without additional mediators, a high bioelectrocatalytic current was generated. Reference experiments with only PEI showed direct electron transfer and catalytic activity of hSO, but these were less pronounced. The application of the polyelectrolyte entrapped quantum dots (QDs) on ITO electrodes provides a compatible surface for enzyme binding with promotion of electron transfer. Variations of the buffer solution conditions, e.g., ionic strength, pH, viscosity, and the effect of oxygen, were studied in order to understand intramolecular and heterogeneous electron transfer from hSO to the electrode. The results are consistent with a model derived for the enzyme by using flash photolysis in solution and spectroelectrochemistry and molecular dynamic simulations of hSO on monolayer modified gold electrodes. Moreover, for the first time a photoelectrochemical electrode involving immobilized hSO is demonstrated where photoexcitation of the CdS/hSO-modified electrode lead to an enhanced generation of bioelectrocatalytic currents upon sulfite addition. Oxidation starts already at the redox potential of the electron transfer domain of hSO and is greatly increased by application of a small overpotential to the CdS/hSO-modified ITO. PMID- 26357960 TI - The role of gene-environment interactions in the development of food allergy. AB - The rates of IgE-mediated food allergy have increased globally, particularly in developed countries. The rising incidence is occurring more rapidly than changes to the genome sequence would allow, suggesting that environmental exposures that alter the immune response play an important role. Genetic factors may also be used to predict an increased predisposition to these environmental risk factors, giving rise to the concept of gene-environment interactions, whereby differential risk of environmental exposures is mediated through the genome. Increasing evidence also suggests a role for epigenetic mechanisms, which are sensitive to environmental exposures, in the development of food allergy. This paper discusses the current state of knowledge regarding the environmental and genetic risk factors for food allergy and how environmental exposures may interact with immune genes to modify disease risk or outcome. PMID- 26357961 TI - One-pot synthesis of crosslinked amphiphilic polycarbonates as stable but reduction-sensitive carriers for doxorubicin delivery. AB - In this paper, we first synthesized a novel disulfide-coupled bis-(cyclic carbonate) (TDCSS) monomer. After ring-opening co-polymerization (ROP) of TDCSS and trimethylene carbonate (TMC) initiated by mono-methoxyl poly(ethylene glycol), the crosslinked reduction-sensitive copolymer PEG-P(TMC-co-TDCSS) was obtained via a facile one-step procedure for efficient delivery of doxorubicin (DOX) into cancer cells. To serve as controls, PEG-P(TMC-co-TDCCC), which has an analogous structure without disulfide bond, and a linear polymer PEG-PTMC were also prepared. The copolymers could self-assemble to form nano-sized micelles in an aqueous solution. As compared to PEG-PTMC, crosslinked PEG-P(TMC-co-TDCSS) and PEG-P(TMC-co-TDCCC) showed lower CMC values and thus induced a much better micelle-forming ability. In vitro release studies revealed that the drug release behavior of DOX-loaded PEG-P(TMC-co-TDCSS) micelles, which could be accelerated in the presence of 10 mM dithiothreitol (DTT), showed a similar trend in the absence of DTT compared to DOX-loaded PEG-P(TMC-co-TDCCC) micelles. Furthermore, confocal laser scanning microscopy (CLSM) indicated that DOX-loaded PEG-P(TMC-co TDCSS) micelles were efficiently internalized into HeLa cells, releasing DOX into the cytoplasm after which the drug finally entered the nuclei, while MTT assays also demonstrated potent cytotoxic activity against HeLa cells. DOX was mainly located in the cytoplasm for reduction-insensitive PEG-P(TMC-co-TDCCC) and PEG PTMC controls. PMID- 26357962 TI - Validation of a Simple Thyroid Cancer Dosimetry Model Based on the Fractional Whole-Body Retention at 48 Hours Post-Administration of (131)I. AB - BACKGROUND: Standard dosimetric methods to determine the maximum tolerated activity (MTA) of (131)I for the treatment of metastatic, well-differentiated thyroid cancer (DTC) are time-consuming and require complex analysis. As a result, reliable, accurate, and simplified methods are desirable. The objective of this study was to evaluate the validity of a simple regression dosimetry model. METHOD: Previously, the authors reported a bi-exponential model for estimating the MTA of (131)I for the treatment of metastatic DTC based on a limit of 2 Gy to the blood. This model uses the patient's body surface area (BSA) along with the fractional whole-body retention (WBR) at 48 hours following oral administration of a diagnostic dosage of (131)I. A bi-exponential regression model was developed between the MTA normalized to the patient's BSA and the percent retention value at the 48-hour time point (R): MTA (GBq)/BSA (m(2)) = (13.91 . e(-0.0387R) + 42.33 . e(-0.8522R)). In this study, the same model was applied to a different set of adult patients referred for dosimetry and possible (131)I treatment of DTC under conditions of thyroid hormone withdrawal or recombinant human thyrotropin (rhTSH) stimulation. All patients (n = 170; 96 female) referred to the authors' clinic for dosimetry and possible (131)I treatment for metastatic DTC during the collection period were included in this study, apart from those undergoing renal dialysis. The MTA predicted (MTAp) using the model described above was compared to the measured MTA (MTAm), with statistical analysis performed using ProStat v4.5. RESULTS: In this group, the MTAm ranged from 2.3 to 41.1 GBq. The linear correlation between the MTAp and MTAm was excellent (r = 0.96), with an average deviation of only +/- 1.2%. However, to avoid overdosing a patient on the basis of the MTAp, a weighting factor (<1.0) should be applied (e.g., using a value of 0.7 would result in only one patient receiving a prescribed activity of (131)I that exceeded the MTAm [<3%]). CONCLUSIONS: The % 48-hour WBR as determined by the bi-exponential function noted herein with reasonable restrictions has been validated as a reliable simplified dosimetry model. PMID- 26357965 TI - Anti-C1q antibody in patients with lupus nephritic flare: 18-month follow-up and a nested case-control study. AB - OBJECTIVES: A prospective cohort was conducted to investigate the association of anti-C1q antibody and lupus/lupus nephritis (LN) flare. METHODS: Sixty-nine consecutive patients with systemic lupus erythematosus were enrolled and followed up for 18 months. Anti-C1q was recorded at the first visit and at the time of flare. For patients with flare, age and sex matched SLE patients were considered as the control group (nested case-control study). The predictability of anti-C1q and other laboratory indices for LN flare during the 18-month follow-up was calculated. RESULTS: Fourteen out of sixty-nine (20%) had lupus flare. Fourteen patients were chosen as controls. Nine cases and three controls had positive anti C1q at the first visit (p = 0.0001). Twenty-six (38%) and 43 (62%) patients had positive and negative anti-C1q antibody at the first visit, respectively, of whom 9 (34.5%) and 3 (7%) patients developed LN flare in the next 18 months (p = 0.003). Anti-C1q and 24-hour urine protein were found as the main predictors of LN flare. The positive and negative predictive values of anti-C1q for LN flare were 35% and 93%, respectively. Predictive values of positive anti-C1q/low C3 together were 60% and 96%, respectively. CONCLUSION: The combination of positive anti-C1q/low C3 had the highest reasonable predictive values for LN flare. PMID- 26357964 TI - Macitentan inhibits the transforming growth factor-beta profibrotic action, blocking the signaling mediated by the ETR/TbetaRI complex in systemic sclerosis dermal fibroblasts. AB - INTRODUCTION: Systemic sclerosis (SSc) is a complex and not fully understood autoimmune disease associated with fibrosis of multiple organs. The main effector cells, the myofibroblasts, are collagen-producing cells derived from the activation of resting fibroblasts. This process is regulated by a complex repertoire of profibrotic cytokines, and among them transforming growth factor beta (TGF-beta) and endothelin-1 (ET-1) play a major role. In this paper we show that TGF-beta and ET-1 receptors co-operate in myofibroblast activation, and macitentan, an ET-1 receptor antagonist binding ET-1 receptors, might interfere with both TGF-beta and ET-1 pathways, preventing myofibroblast differentiation. METHODS: Fibroblasts isolated from healthy controls and SSc patients were treated with TGF-beta and ET-1 and successively analyzed for alpha smooth muscle actin (alpha-SMA) and collagen (Col1A1) expression and for the Sma and Mad Related (SMAD) phosphorylation. We further tested the ability of macitentan to interfere with these process. Furthermore, we silenced ET-1 and endothelin-1 receptor A expression and evaluated the formation of an ET-1/TGF-beta receptor complex by immunoprecitation assay. RESULTS: We showed myofibroblast activation in SSc fibroblasts assessing the expression of alpha-SMA and Col1A1, after stimulation with TGF-beta and ET-1. Macitentan interfered with both ET-1- and TGF-beta induced fibroblast activation. To explain this unexpected inhibitory effect of macitentan on TGF-beta activity, we silenced ET-1 expression on SSc fibroblasts and co-immunoprecipitated these two receptors, showing the formation of an ET 1/TGF-beta receptor complex. CONCLUSIONS: During SSc, ET-1 produced by activated endothelia contributes to myofibroblast activation using TGF-beta machinery via an ET-1/TGF-beta receptor complex. Macitentan interferes with the profibrotic action of TGF-beta, blocking the ET-1 receptor portion of the ET-1/TGF-beta receptor complex. PMID- 26357966 TI - Simultaneous Determination of Perfluorinated Compounds in Edible Oil by Gel Permeation Chromatography Combined with Dispersive Solid-Phase Extraction and Liquid Chromatography-Tandem Mass Spectrometry. AB - A simple analytical method was developed for the simultaneous analysis of 18 perfluorinated compounds (PFCs) in edible oil. The target compounds were extracted by acetonitrile, purified by gel permeation chromatography (GPC) and dispersive solid-phase extraction (DSPE) using graphitized carbon black (GCB) and octadecyl (C18), and analyzed by liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ES-MS/MS) in negative ion mode. Recovery studies were performed at three fortification levels. The average recoveries of all target PFCs ranged from 60 to 129%, with an acceptable relative standard deviation (RSD) (1-20%, n = 3). The method detection limits (MDLs) ranged from 0.004 to 0.4 MUg/kg, which was significantly improved compared with the existing liquid-liquid extraction and cleanup method. The method was successfully applied for the analysis of all target PFCs in edible oil samples collected from markets in Beijing, China, and the results revealed that C6-C10 perfluorocarboxylic acid (PFCAs) and C7 perfluorosulfonic acid PFSAs were the major PFCs detected in oil samples. PMID- 26357967 TI - Should Governments engage health insurance intermediaries? A comparison of benefits with and without insurance intermediary in a large tax funded community health insurance scheme in the Indian state of Andhra Pradesh. AB - BACKGROUND: A peculiar phenomenon of engaging insurance intermediaries for government funded health insurance schemes for the poor, not usually found globally, is gaining ground in India. Rajiv Aarogyasri Scheme launched in the Indian state of Andhra Pradesh, is first largest tax funded community health insurance scheme in the country covering more than 20 million poor families. Aarogyasri Health Care Trust (trust), the scheme administrator, transfers funds to hospitals through two routes one, directly and the other through an insurance intermediary. The objective of this paper is to find out if engaging an insurance intermediary has any effect on cost efficiency of the insurance scheme. METHODS: We used payment data of RAS for the period 2007-12, to find out the influence of insurance intermediary on the two variables, benefit cost ratio defined as benefit payment divided by premium payment, and claim denial ratio defined as benefit payment divided by treatment cost. Relationship between scheme expenditure and number of beds empanelled under the scheme is examined. OLS regression is used to perform all analyses. RESULTS: We found that adding an additional layer of insurance intermediary between the trust and hospitals reduced the benefit cost ratio under the scheme by 12.2% (p-value = 0.06). Every addition of 100 beds under the scheme increases the scheme payments by US$ 0.75 million (p-value < 0.001). The gap in claim denial ratio between insurance and trust modes narrowed down from 2.84% in government hospitals to 0.41% in private hospitals (p-value < 0.001). CONCLUSIONS: The scheme is a classic case of Roemer's principle in operation. Introduction of insurance intermediary has the twin effects of reduction in benefit payments to beneficiaries, and chocking fund flow to government hospitals. The idea of engaging insurance intermediary should be abandoned. PMID- 26357968 TI - Steps ahead in the treatment of advanced colorectal cancer: past, current and possible future scenarios. PMID- 26357969 TI - Hybrid Hairy Janus Particles Decorated with Metallic Nanoparticles for Catalytic Applications. AB - We report for the first time on the design of an advanced hairy hybrid Janus-type catalyst, which is comprised of an inorganic silica core covered with two distinct polymeric shells (hydrophilic and hydrophobic) on its opposite sides, while the catalytic species (in our case silver or gold nanoparticles) are immobilized directly into the hydrophilic stimuli-responsive polymer shell. The primary 200 nm large Janus particles with poly(acrylic acid) serving as the hydrophilic and polystyrene as the hydrophobic polymer were synthesized through a Pickering emulsion and a combination of "grafting from"/"grafting to" approaches. The incorporation of silver and gold nanoparticles within the hydrophilic polymer shell was achieved by infiltrating the respective metal ions into the polymer matrix, and nanoparticles were formed upon the addition of a reducing agent (triethylamine). Plasmon absorptions typical for silver and gold nanostructures were observed on the functionalized Janus particles using UV-vis spectroscopy. The respective systems were investigated by TEM and cryo-TEM revealing that the incorporated nanoparticles are selectively localized on the poly(acrylic acid) side of the Janus particles. The efficiency of the catalyst as well as the accessibility of the incorporated nanoparticles was tested on the reduction of Methylene Blue, Eosin Y, and 4-nitrophenol as convenient benchmark systems. Ultimately, the hairy Janus particles with immobilized Ag or Au nanoparticles efficiently catalyzed the respective reactions by applying extremely low amounts of catalyst. Finally, we demonstrated several advantages of the use of JPs with immobilized metallic nanoparticles, which are (i) JPs stabilize the emulsions, (ii) the emulsion can be destabilized by utilizing responsive properties of the JPs, and (iii) JPs can easily be recovered after reaction and reused again. PMID- 26357971 TI - Spin configuration in isolated FeCoCu nanowires modulated in diameter. AB - Cylindrical Fe28Co67Cu5 nanowires modulated in diameter between 22 and 35 nm are synthesized by electroplating into the nanopores of alumina membranes. High sensitivity MFM imaging (with a detection noise of 1 MUN m(-1)) reveals the presence of single-domain structures in remanence with strong contrast at the ends of the nanowires, as well as at the transition regions where the diameter is modulated. Micromagnetic simulations suggest that curling of the magnetization takes place at these transition sites, extending over 10-20 nm and giving rise to stray fields measurable with our MFM. An additional weaker contrast is imaged, which is interpreted to arise from inhomogeneities in the nanowire diameter. PMID- 26357970 TI - Unsolved challenges in diuretic therapy for acute heart failure: a focus on diuretic response. AB - Loop diuretics represent the mainstay of management of patients hospitalized for heart failure (HF). Diuretic resistance is commonly encountered in clinical practice, but limited evidence-based approaches are available to address it. Recent clinical investigations have proposed common definitions of diuretic response: a change in body weight, net fluid loss or total urinary output to 40 mg of furosemide dose equivalents. Poor diuretic response is characterized by features of advanced HF and atherosclerosis and is independently associated with poor in-hospital and post-discharge outcomes. A number of adjunctive or combination decongestion therapies are available to overcome diuretic resistance, but high-quality prospective data supporting these approaches are lacking. Once a definition has been standardized and accepted, diuretic response may represent an important inclusion criteria and end point in upcoming clinical trials in hospitalized HF to help define an optimal, tailored approach to this challenging clinical entity. PMID- 26357963 TI - Clinical and inflammatory characteristics of the European U-BIOPRED adult severe asthma cohort. AB - U-BIOPRED is a European Union consortium of 20 academic institutions, 11 pharmaceutical companies and six patient organisations with the objective of improving the understanding of asthma disease mechanisms using a systems biology approach.This cross-sectional assessment of adults with severe asthma, mild/moderate asthma and healthy controls from 11 European countries consisted of analyses of patient-reported outcomes, lung function, blood and airway inflammatory measurements.Patients with severe asthma (nonsmokers, n=311; smokers/ex-smokers, n=110) had more symptoms and exacerbations compared to patients with mild/moderate disease (n=88) (2.5 exacerbations versus 0.4 in the preceding 12 months; p<0.001), with worse quality of life, and higher levels of anxiety and depression. They also had a higher incidence of nasal polyps and gastro-oesophageal reflux with lower lung function. Sputum eosinophil count was higher in severe asthma compared to mild/moderate asthma (median count 2.99% versus 1.05%; p=0.004) despite treatment with higher doses of inhaled and/or oral corticosteroids.Consistent with other severe asthma cohorts, U-BIOPRED is characterised by poor symptom control, increased comorbidity and airway inflammation, despite high levels of treatment. It is well suited to identify asthma phenotypes using the array of "omic" datasets that are at the core of this systems medicine approach. PMID- 26357972 TI - Surgical approach to primary tumors of the chest wall in children and adolescents: 30 years of mono-institutional experience. AB - AIMS AND BACKGROUND: Chest wall reconstruction after surgical resection for malignancies in children is a challenge for surgeons because of growth-related complications. The aim of this study is to analyze the surgical treatment and outcomes of 30 pediatric and adolescent patients treated at Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, over a 30-year period. METHODS: Pediatric patients undergoing chest wall resection were retrospectively reviewed and selected for malignant primary tumor. Endpoints were survival, recurrences, and long-term results. We also reported the use of the innovative rib-like technique in 2 young patients. RESULTS: Twenty-one patients were male. Median age was 13.7 years. Eleven patients (37%) presented with a chest wall mass. Twenty six (87%) had Ewing sarcoma family tumors. Twenty-eight (94%) received neoadjuvant chemotherapy after histologic diagnosis. One rib was resected in 13 cases; 2 or 3 contiguous ribs in 8 cases. No postoperative mortality was observed and the complication rate was 40%. Overall survival was 85.2% (95% confidence interval [CI] 65.2%-94.2%) at 5 and 10 years. Relapse occurred in 7 patients. The 5-year disease-free survival rate was 82% (95% CI 62%-92%). CONCLUSIONS: Long term survival is achievable for chest wall tumors in a high-volume referral center where a multimodal treatment should be set to reach the best result. As advances in medical treatment have increased survival, surgical techniques must ensure a lasting functional result. When refining the reconstruction techniques, such as the rib-like approach, it is necessary to expand the options of curative surgery for young patients. PMID- 26357973 TI - A targeted approach to genetic counseling in breast cancer patients: the experience of an Italian local project. AB - AIMS AND BACKGROUND: Patients with hereditary breast cancer (BC) may benefit from genetic counseling and testing for detection of causative mutations, definition of therapeutic and preventive strategies, and identification of at-risk relatives. Italy has few oncogenetic centers and genetic evaluation of all patients with BC is not feasible. Moreover, lack of uniformity in the selection of patients generates inappropriate referral to the geneticist. We designed a model that may represent a reproducible way to select patients at risk for hereditary BC, with the aims of rationalizing access to genetic centers and improving clinical management and surveillance. METHODS: The genetic unit of a Cancer Center and the Departments of Oncology from 2 public Hospitals in Milan were involved in the project. After training sessions at the genetic unit, operators from the 2 hospitals evaluated all patients with BC attending a first oncologic visit, through a specific interview. Patients considered at risk of hereditary BC attended counseling at the genetic unit. RESULTS: Of 419 patients, 61 (14.5%) were eligible for genetic counseling after the interview. Of these, 46 (10.9%) strictly met testing criteria. Overall, 52 (12.4%) patients underwent genetic counseling and 47 were tested for BRCA1/BRCA2 mutation. After genetic test results, the available options for treatment/surveillance were discussed by a multidisciplinary team, according to the level of genetic risk. CONCLUSIONS: It is possible to improve the process of referring patients with suspected hereditary BC for genetic risk assessment. The application of clinical screening reduced the genetics unit's workload and enabled optimization of time and resources. PMID- 26357974 TI - The natural compound gambogic acid radiosensitizes nasopharyngeal carcinoma cells under hypoxic conditions. AB - AIMS: Hypoxia is an important factor that causes decreased local disease control as well as increased distant metastases and resistance to radiotherapy in patients with advanced nasopharyngeal carcinoma (NPC). Gambogic acid (GA), the major active ingredient of gamboge, exerts antitumor effects in vitro and in vivo. However, the molecular mechanism by which GA inhibits tumor radioresistance remains unclear. The present study aimed to investigate the radiosensitizing effects of GA on NPC and explore the underlying mechanisms. MATERIALS AND METHODS: CNE-1 and CNE-2 cells exposed to hypoxia and radiation were treated with GA at different concentrations. CCK-8 assay, clonogenic assay, and flow cytometry were performed to analyze cell proliferation, colony formation, apoptosis, and cell cycle. The expression levels of hypoxia-inducible factor-1alpha (HIF 1alpha), Bcl-2, Bax, caspase-3, cyclin B1/p-cdc2 and gamma-H2AX were assessed using Western blot and/or immunofluorescence analysis. RESULTS: Results of the CCK-8 assay, clonogenic assay, and flow cytometry showed that treatment of NPC cells with growth-suppressive concentrations of GA resulted in G2/M phase arrest and apoptosis. Western blot analysis demonstrated that GA-induced cell cycle arrest and apoptosis in CNE-2 cells was associated with upregulated expression of caspase-3 and Bax and downregulated expression of Bcl-2 and cyclin B1/p-cdc2 in hypoxia. Treatment with GA markedly decreased the expression of HIF-1alpha under hypoxic conditions. CONCLUSIONS: The results of this study suggest that GA efficiently radiosensitizes NPC cells and the effect may be significant in hypoxic conditions. PMID- 26357975 TI - Mammographic findings after reshaping with autoprosthesis in women undergoing contralateral breast reconstruction and mastectomy. AB - AIMS AND BACKGROUND: Breast reduction and mastopexy combined with inferior dermo lipo-glandular flap (autoprosthesis) gives good breast shape, long-term projection, and upper pole fullness. We assess the impact on breast oncologic surveillance compared to other techniques. METHODS: A total of 105 patients who underwent mastectomy and reconstruction were divided into 3 groups of 35 patients each: groups 1 and 2 include patients with contralateral breast symmetrization performed with and without autoprosthesis technique, respectively. Group 3 is a control group without contralateral breast reshaping. On mammography, edema, skin thickening, architectural distortion, and calcifications were recorded, as well as further diagnostic examinations, biopsies, and surgical treatments required. RESULTS: Statistically significant differences (p<0.001) in the first follow-up mammography between groups 1 and 2 were stromal edema (6% vs 51%) and architectural distortion (74% vs 63%). The latest findings meant architectural distortion also have significant difference (p<0.001) in the last mammography (79% vs 66%). Microcalcification has statistically significant difference (p<0.001) in the latest postsurgical mammography, increased in group 1. Skin thickening had a similar course in either group. Mammography follow-up was not impaired in most cases notwithstanding the parenchyma distortion as compared with mammography after breast-conserving surgery. Four core biopsies were performed in both groups: 3 new breast cancers and 1 benign epithelial hyperplasia were found. CONCLUSIONS: No difficulties were found impairing mammographic evaluation in patients treated with autoprosthesis as compared to other techniques. PMID- 26357976 TI - A cross-sectional survey on wounds in horses in New Zealand. AB - AIM: To determine the frequency and type of skin wounds encountered by New Zealand veterinarians in their equine patients, the duration and estimated costs of treatment as well as the expected outcomes for these wounds. METHODS: An online survey was sent to all veterinarians registered with the New Zealand Equine Veterinary Association. The survey comprised questions on the location and experience of respondents, the number of wound-related cases in relation to the total equine caseload, the type and anatomical location of wounds treated, the frequency, duration and costs of treatments, the outcome of wound treatment and an estimate of the most common causes of death or euthanasia in their equine patients. RESULTS: The survey response rate was 110/262 (41.9%). The median number of equine cases seen by respondents was 20 (interquartile range (IQR) 6 60) per month; of these, five (IQR 2-10) were wound related. Wounds ranked third after lameness and respiratory disease for the relative frequency with which respondents encountered them. Of 102 respondents 59 (58%) reported that their clients frequently treated wounds incurred by their horse without consulting a veterinarian. Wounds on the distal limb, whether involving only the skin or also deeper structures, were reported by 86/101 (85%) respondents as the most frequently encountered. Wounds in this location also incurred the longest treatment period and were the most prone to develop complications. Finally, wounds ranked second, after colic, as the most common cause of death/euthanasia in the veterinary respondents' equine patients. CONCLUSIONS: The data obtained via the survey indicate that skin wounds, particularly on the distal limb, are a common occurrence in horses in New Zealand and, when they involve structures underlying the skin, are costly and time-consuming to manage and may lead to decreased performance, retirement or euthanasia. Consequently, we recommend that more effort be devoted to the education of equine veterinarians and owners, and that appropriate research funds be allocated to help improve patient outcomes. PMID- 26357977 TI - Increasing Carotenoid Bioaccessibility from Yellow Peppers Using Excipient Emulsions: Impact of Lipid Type and Thermal Processing. AB - Many phytochemicals from fruits and vegetables exert biological activities that may be beneficial to human health, but these benefits are not fully realized because of their poor oral bioavailability. The objective of this research was to establish the potential of excipient emulsions to increase carotenoid bioaccessibility from raw and cooked yellow peppers using a gastrointestinal model that included oral, gastric, and intestine phases. The influence of oil type (medium chain triglycerides, MCT; long chain triglycerides, LCT; and, indigestible orange oil, OO) on microstructural changes, particle properties, lipid digestibility, and carotenoid bioaccessibility was investigated. Oil type had a major impact, with carotenoid bioaccessibility decreasing in the following order: LCT > MCT > OO > control (no oil). Conversely, thermal treatment (raw versus boiled) had little influence on carotenoid bioaccessibility. These results will facilitate the rational design of excipient emulsions that boost the bioavailability of phytochemicals in fruits and vegetables. PMID- 26357979 TI - Worldly wise: The challenges for global professionals. PMID- 26357978 TI - Health literacy in an urban elderly East-German population - results from the population-based CARLA study. AB - BACKGROUND: Health literacy (HL) has gained increasing attention in public health research. However, until now research was mainly focused on clinical settings rather than on the general population. Due its relation to social determinants and health outcomes, HL is of special interest in epidemiological studies. The aim of the present study was therefore to describe HL among an elderly general high-risk population, to analyze the potential contributing factors of HL, and to analyze the impact of HL on health-related outcomes. METHODS: We used data from the CARLA Study, which is a prospective population-based cohort study of the elderly general population of the city of Halle (Saale) in Eastern Germany. The short version of the HLS-EU Questionnaire (HLS-EU-Q16) was administered with 1,107 subjects aged between 55 and 91 year old. A HL score ranging from 0 to 50 points was computed and classified according to the recommendation of the HLS-EU project. Socio-economic as well as health-related variables were determined during the standardized interview and clinical examination. We calculated linear as well as logistic regression models in order to analyze the association between HL and health-related outcomes as well as potential influencing factors of HL. RESULTS: Overall, the HL score was 36.9 (SD 6.9). Among all subjects, 4 % showed inadequate HL, 23 % problematic HL, 50 % sufficient HL, and 23 % excellent HL. HL was positively associated with educational level, net household income, and self perceived social position. Further, we found an increase of HL with age (beta = 0.10; 95 % CL 0.05; 0.15) and a lower HL score among women compared with men (Diff = -1.4; 95 % CL -2.2; -0.6). An inverse association was observed between HL and diabetes among both sexes (OR 0.93; 95 % CL 0.93; 0.98), between HL and myocardial infarction among women, and between HL and stroke among men. CONCLUSIONS: In this elderly general Eastern German population, we found higher HL score values compared with previous studies using the same questionnaire. HL was associated with socio-economic status. Furthermore, this cross-sectional study could show associations between HL and different health-related outcomes even after adjustment for educational level. However, further research is needed in order to evaluate the impact of HL on health-related outcomes using longitudinal data derived from the general population. PMID- 26357981 TI - Metastatic gastric cancer in the last two decades: goals achieved and future promises. PMID- 26357982 TI - A Perylene Diimide Crystal with High Capacity and Stable Cyclability for Na-Ion Batteries. AB - Organic Na-host materials have are now actively pursued as an attractive alternative to conventional transition-metal compounds for development of sustainable sodium ion batteries; however, most of the organic compounds reported so far suffer from their low reversible capacity and poor cyclability. Here, we report a simple perylene diimide, 3,4,9,10-perylene-bis(dicarboximide) (PTCDI), which demonstrates remarkable electrochemical performances as an organic cathode for Na-ion batteries. With the high density of redox-active carbonyl groups in a stable pi-conjugated structure, the PTCDI molecule can undergo a two-electron redox reaction with reversible insertion/extraction of 2 Na(+) ions per molecular unit, demonstrating a high capacity of 140 mAh g(-1), a strong rate performance with a reversible capacity of 103 mAh g(-1) at 600 mA g(-1) (5 C,1 C = 120 mA g( 1)) and a long-term cyclability with 90% capacity retention over 300 cycles. Because this PTCDI material is commercially available and nontoxic, it may serve as a new alternative cathode for Na-ion battery applications. PMID- 26357983 TI - Ebstein anomaly review: what's now, what's next? AB - Ebstein anomaly accounts for 1% of all congenital heart disease. It is a right ventricular myopathy with failure of tricuspid valve delamination and highly variable tricuspid valve morphology that usually results in severe regurgitation. It is the only congenital heart lesion that has a range of clinical presentations, from the severely symptomatic neonate to an asymptomatic adult. Neonatal operation has high operative mortality, whereas operation performed beyond infancy and into adulthood has low operative mortality. Late survival and quality of life for hospital survivors are excellent for the majority of patients in all age brackets. Atrial tachyarrhythmias are the most common late complication. There have been more techniques of tricuspid repair reported in the literature than any other congenital or acquired cardiac lesion. This is largely due to the infinite anatomic variability encountered with this anomaly. The cone reconstruction of Ebstein anomaly can achieve near anatomic restoration of the tricuspid valve anatomy. Early and intermediate results with these repairs are promising. Reduced right ventricular function continues to be a challenge for some patients, as is the need for reoperation for recurrent tricuspid regurgitation. The purpose of this article is to outline the current standard of care for diagnosis and treatment of Ebstein anomaly and describe innovative strategies to address poor right ventricular function and associated right-sided heart failure. PMID- 26357984 TI - Electrical properties of ZnO single nanowires. AB - We have investigated the electrical resistance R(T) of ZnO nanowires of ~ 400 nm diameter as a function of temperature, between 30 K and 300 K, and frequency in the range 40 Hz to 30 MHz. The measurements were done on the as-prepared and after low-energy proton implantation at room temperature. The temperature dependence of the resistance of the wire, before proton implantation, can be well described by two processes in parallel. One process is the fluctuation induced tunneling conductance (FITC) and the other the usual thermally activated process. The existence of a tunneling conductance was also observed in the current-voltage ([Formula: see text]) results, and can be well described by the FITC model. Impedance spectroscopy measurements in the as-prepared state and at room temperature, indicate and support the idea of two contributions of these two transport processes in the nanowires. Electron backscatter diffraction confirms the existence of different crystalline regions. After the implantation of H(+) a third thermally activated process is found that can be explained by taking into account the impurity band splitting due to proton implantation. PMID- 26357985 TI - Telemedicine: are we advancing the science? PMID- 26357986 TI - Trends in the psychopharmacological treatment of bipolar disorder: a nationwide register-based study. AB - OBJECTIVE: In bipolar disorder, treatment with antidepressants without concomitant use of mood stabilisers (antidepressant monotherapy) is associated with development of mania and rapid cycling and is therefore not recommended. The present study aimed to investigate the psychopharmacological treatment patterns in bipolar disorder over time, with a focus on antidepressant monotherapy. METHODS: Cohort study with annual cross-sectional assessment of the use of psychotropic medications between 1995 and 2012 for all Danish residents aged 10 years or older with a diagnosis of bipolar disorder registered in the Danish Psychiatric Central Research Register. Users of a given psychotropic medication were defined as individuals having filled at least one prescription for that particular medication in the year of interest. RESULTS: We identified 20 618 individuals with bipolar disorder. The proportion of patients with bipolar disorder using antidepressants, atypical antipsychotics and anticonvulsants increased over the study period, while the proportion of patients using lithium, typical antipsychotics and benzodiazepines/sedatives decreased. The proportion of patients treated with antidepressant monotherapy decreased from 20.5% in 1997 to 12.1% in 2012, and among antidepressant users, the proportion in monotherapy decreased from 47.7% to 23.9%, primarily driven by a decrease in the use of tricyclic antidepressants. CONCLUSION: The results show an increase in the proportion of patients with bipolar disorder being treated with antidepressants in the period from 1997 to 2012. However, in accordance with international treatment guidelines, the extent of antidepressant monotherapy decreased during the same period. PMID- 26357987 TI - Medication reviews are useful, but the model needs to be changed: Perspectives of Aboriginal Health Service health professionals on Home Medicines Reviews. AB - BACKGROUND: The Australian Home Medicines Review (HMR) program consists of a pharmacist reviewing a patient's medicines at his or her home and reporting findings to the patient's general practitioner (GP) to assist optimisation of medicine management. Previous research has shown that the complex HMR program rules impede access to the HMR program by Aboriginal and Torres Strait Islander clients. This study explores the attitudes and perceptions of health professional employees working within Aboriginal Health Services (AHSs) towards the HMR program. The goal was to identify how the HMR program might better address the needs of Aboriginal and Torres Strait Islander people. METHODS: Thirty-one semi structured interviews were conducted with health professionals at 11 diverse AHSs. Fourteen Aboriginal Health Workers (AHWs), five nurses, one manager and 11 GPs were interviewed. Interviews were recorded, de-identified and transcribed verbatim. Transcripts were coded and analysed for themes that recurred throughout the interviews. RESULTS: This study identified a number of barriers to provision of HMRs specific to Aboriginal and Torres Strait Islander clients. These included paternalistic attitudes of health professionals to clients, heightened protection of the GP-client relationship, lack of AHS-pharmacist relationships, need for more culturally responsive pharmacists and the lack of recognition of the AHS's role in implementation of culturally effective HMRs. Changes to the HMR model, which make it more effective and culturally appropriate for Aboriginal and Torres Strait Islander people, were recommended. Improved relationships between GPs and pharmacists, between pharmacists and AHSs, and between pharmacists and Aboriginal and Torres Strait Islander clients were identified as key to increasing HMRs for Aboriginal and Torres Strait Islander people. CONCLUSIONS: Aboriginal Health Services are well-placed to be the promoters, organisers, facilitators and implementers of health programs, such as HMR, for Aboriginal and Torres Strait Islander clients. Embedding a pharmacist within an AHS addresses many of the barriers to HMRs. It ensures pharmacists are culturally mentored and that they build strong relationships with health professionals and clients. The HMR program rules need to be changed significantly if medication review is to be an effective tool for improving medication safety and adherence for Aboriginal and Torres Strait Islander people. PMID- 26357989 TI - Metabolism of (Z)-(1R,3R)-Profluthrin in Rats. AB - When [benzyl-alpha-(14)C]-labeled (Z)-(1R,3R)-profluthrin (2,3,5,6-tetrafluoro-4 methylbenzyl (Z)-(1R,3R)-2,2-dimethyl-3-(prop-1-enyl) cyclopropanecarboxylate, a newly developed pyrethroid) was administered orally to rats at 1 mg/kg, around 70% was absorbed, metabolized, and mainly excreted into urine within 48 h. Radioactivity in plasma reached Cmax at 6-8 h, and decreased (half-life; 37-52 h). A similar tendency was observed also in tissues. Absorption rate was slightly lower at high dose, while kinetics and distribution did not change. Eight metabolites were detected in urine and one in feces. Most of the (14)C in feces was unabsorbed (Z)-(1R,3R)-profluthrin. The main metabolic reactions were ester cleavage, hydroxylation of the methyl group on the C4-position of the benzene ring, and its glucuronidation or oxidation to carboxylic acid. Oxidation of the geminal dimethyl on the cyclopropane-C2 to carboxylic acid, oxidation followed by hydration of the propenyl double bond, and omega-oxidation to carboxylic acid and mercapturic acid conjugation of the benzyl alcohol were observed as minor reactions. PMID- 26357990 TI - Associations of diabetes mellitus with orthopaedic infections. AB - BACKGROUND: Clinical experience suggests that a high proportion of orthopaedic infections occur in persons with diabetes. METHODS: We reviewed several databases of adult patients hospitalized for orthopaedic infections at Geneva University Hospitals from 2004 to 2014 and retrieved 2740 episodes of infection. RESULTS: Overall, diabetes was noted in the medical record for 659 (24%) of these cases. The patients with, compared with those without, diabetes had more than five times more foot infections (274/659 [42%] vs 155/2081 [7%]; p < 0.01) and a significantly higher serum C-reactive protein level at admission (median 96 vs 70 mg/L; p < 0.01). Diabetic patients were older (median 67 vs 52 years; p < 0.01), more often male (471 [71%] vs 1398 [67%]; p = 0.04), and had more frequent polymicrobial infections (219 [37%] vs 353 [19%]; p < 0.01), including more gram negative non-fermenting rods (90 [15%] vs 168 [9%]; p < 0.01). Excluding foot infections from these analyses did not change the statistically significant differences. Diabetes was present in 17% of all infected orthopaedic patients without foot involvement. In Geneva canton, the overall prevalence of diabetes is estimated at 5.1%, while we have found that the prevalence is 13% in our hospitalized adults. CONCLUSIONS: Diabetes is present in 24% of all adult patients hospitalized for surgery for an orthopaedic infection, a prevalence that is several times higher than for the general population and twice as high as that for the population of hospitalized patients. Compared with non-diabetics, patients with diabetes have significantly more infections that are polymicrobial, including gram-negative non-fermenting rods. PMID- 26357991 TI - Creating a whole institution approach to in-service training in sexual and reproductive health in Uganda. AB - BACKGROUND: Uganda has one of the world's highest fertility rates, and high unmet need for family planning, even when clients have contact with health facilities. Misconceptions about contraceptive side effects and inadequate training for healthcare workers contribute to this. AIM: To develop and evaluate in-service training for family planning, across a whole institution. DESIGN: Course evaluation. Impact on services. METHODS: Following a needs assessment, two courses were developed, adapting WHO's Training Resource Package for Family Planning. All staff were offered level 1 training (five 1 h sessions). The 30 h level 2 course aimed to train clinical staff to certificate level; assessed by written exam, consultation skills and presentations. Quantitative evaluation assessed changes in pre-course and post-course knowledge and confidence scores. Participant feedback was analysed thematically. RESULTS: Of the hospital's 76 clinical staff, 44 attended some training. Of these, 21 attended and 19 completed level 2. Mean knowledge scores increased from 15.9 (SD 4.5) to 20.8 (SD 3.1)/26 (95% CI 4.9 (2.5-7.2)). Confidence rose from 8.1 (SD 1.5) to 9.5 (SD 0.5) (95% CI 1.4 (0.7-2.2)). Nine were accredited to fit intrauterine devices and implants, and three just implants. Screening for unmet need is being introduced and outreach work aims to overcome barriers to adoption of family planning. CONCLUSIONS: Brief in-service training improves health workers' knowledge and skills, corrects misconceptions and increases the priority given to family planning. When aligned to local need and the culture of the institution, training can prompt moves to address unmet need for family planning. PMID- 26357992 TI - The past, present and future of fertility preservation in cancer patients. AB - Fertility preservation strategies have been developed for men and women whose fertility is compromised for medical reasons, especially in case of cancer therapy. At present, many reliable options for preserving fertility are available. However, a part of these fertility preservation methods, despite being promising, are still considered experimental. Nevertheless, there are still situations where no methods can be offered. Remarkable scientific progress is currently underway to improve available techniques and to develop new technologies to solve problems with current fertility strategies. These new options may drastically change reproductive options for young patients facing germ cell loss and hence sterility. Therefore, oncofertility counseling by a specialist is recommended for all young cancer patients having to undergo treatment that may reduce fertility potential. PMID- 26357993 TI - Bacterial Cellulose Supported Gold Nanoparticles with Excellent Catalytic Properties. AB - Amidoxime surface functionalized bacterial cellulose (AOBC) has been successfully prepared by a simple two-step method without obviously changing the morphology of bacterial cellulose. AOBC has been used as the reducing agent and carrier for the synthesis of gold nanoparticles (AuNPs) that distributed homogeneously on bacterial cellulose surface. Higher content in amidoxime groups in AOBC is beneficial for the synthesis of AuNPs with smaller and more uniform size. The AuNPs/AOBC nanohybrids have excellent catalytic activity for reduction of 4 nitrophenol (4-NP) by using NaBH4. It was found that catalytic activity of AuNPs/AOBC first increases with increasing NaBH4 concentration and temperature, and then leveled off at NaBH4 concentration above 238 mM and temperature above 50 degrees C. Moreover, AuNPs with smaller size have higher catalytic activity. The highest apparent turnover frequency of AuNPs/AOBC is 1190 h(-1). The high catalytic activity is due to the high affinity of 4-NP with AuNPs/AOBC and the reduced product 4-aminophenol has good solubility in water in the presence of AuNPs/AOBC. The catalytic stability of the AuNPs/AOBC was estimated by filling a fluid column contained AuNPs/AOBC and used for continuously catalysis of the reduction of 4-NP by using NaBH4. The column works well without detection of 4-NP in the eluent after running for more than two months, and it is still running. This work provides an excellent catalyst based on bacterial cellulose stabilized AuNPs and has promising applications in industry. PMID- 26357994 TI - ZnO quantum dots-decorated ZnO nanowires for the enhancement of antibacterial and photocatalytic performances. AB - We demonstrate highly antibacterial activities for killing off Staphylococcus aureus and Escherichia coli using ZnO nanowires decorated with ZnO quantum dots (so-called ZnO QDs/NWs) under visible-light irradiation and dark conditions. The average size of the ZnO QDs is in the range of 3-5 nm; these were uniformly dispersed on the ZnO nanowires' surface to form the ZnO QDs/NWs. A significant blue-shift effect was observed using photoluminescence (PL) spectra. The size of the ZnO QDs is strongly dependent on the material's synthesis time. The ZnO QDs/NWs exhibited an excellent photocatalytic activity under visible-light irradiation. The ZnO QDs' active sites (i.e. the O-H bond and Zn(2+)) accelerate the photogenerated-carrier migration from the QDs to the NWs. As a consequence, the electrons reacted with the dissolved oxygen to form oxygen ions and produced hydroperoxyl radicals to enhance photocatalytic activity. The antibacterial activities (as indicated by R-factor-inhibiting activity) of the ZnO QDs/NWs for killing off Staphylococcus aureus and Escherichia coli is around 4.9 and 5.5 under visible-light irradiation and dark conditions, respectively. The hydroxyl radicals served as an efficient oxidized agent for decomposing the organic dye and microorganism species. The antibacterial activities of the ZnO QDs/NWs in the dark may be attributed to the Zn(2+) ions that were released from the ZnO QDs and infused into the microbial solution against the growth of bacteria thus disrupting the microorganism. The highly antibacterial and photocatalytic activity of the ZnO QDs/NWs can be well implanted on a screen window, thus offering a promising solution to inhibit the spread of germs under visible-light and dark conditions. PMID- 26357995 TI - Transcriptome-wide analysis of chromium-stress responsive microRNAs to explore miRNA-mediated regulatory networks in radish (Raphanus sativus L.). AB - MicroRNAs (miRNAs) are small noncoding RNAs that play pivotal roles in plant growth, development and stress response. Chromium (Cr) is one of common environmental contaminants possessing potential health hazards to living organisms. To date, little is known about the regulatory roles of miRNAs in response to Cr stress in radish. To systematically identify Cr-responsive miRNAs and their targets in radish, two sRNA libraries derived from Cr-free (CK) and Cr treated (Cr200) roots were constructed. With Solexa sequencing, 81 known and 72 novel miRNAs were identified, from which 54 known and 16 novel miRNAs were significantly differentially expressed under Cr stress. Several target genes for Cr-responsive miRNAs encode different transcription factor (TF) families, including SPLs, MYBs, ERFs and bZIPs, might regulate corresponding HM-related transcriptional processes in plants. Notably, a few key responsive enzymes or proteins, including HMA, YSL1 and ABC transporter protein were involved in Cr uptake and homeostasis process. Furthermore, the expression patterns of some Cr responsive miRNAs and their targets were validated by RT-qPCR. This study represents the first characterization of Cr-responsive miRNAs and their targets in radish. The outcomes of this study could provide novel insights into miRNA mediated regulatory mechanisms underlying plant response to Cr stress in root vegetable crops. PMID- 26357996 TI - Effects of repeated asenapine in a battery of tests for anxiety-like behaviours in mice. AB - OBJECTIVE: A number of atypical antipsychotic drugs were demonstrated to have anxiolytic effects in patients and in animal models. These effects were mostly suggested to be the consequence of the drugs' affinity to the serotonin system and its receptors. Asenapine is a relatively new atypical antipsychotic that is prescribed for schizophrenia and for bipolar mania. Asenapine has a broad pharmacological profile with significant effects on serotonergic receptors, hence it is reasonable to expect that asenapine may have some anxiolytic effects. The present study was therefore designed to examine possible effects of asenapine on anxiety-like behaviour of mice. METHOD: Male ICR mice were repeatedly treated with 0.1 or 0.3 mg/kg injections of asenapine and then tested in a battery of behavioural tests related to anxiety including the open-field test, elevated plus maze (EPM), defensive marble burying and hyponeophagia tests. In an adjunct experiment, we tested the effects of acute diazepam in the same test battery. RESULTS: The results show that diazepam reduced anxiety-like behaviour in the EPM, the defensive marble burying test and the hyponeophagia test but not in the open field. Asenapine has anxiolytic-like effects in the EPM and the defensive marble burying tests but had no effects in the open-field or the hyponeophagia tests. Asenapine had no effects on locomotor activity. CONCLUSION: The results suggest that asenapine may have anxiolytic-like properties and recommends that clinical trials examining such effects should be performed. PMID- 26357997 TI - 2-Furoylglycine as a Candidate Biomarker of Coffee Consumption. AB - Specific and sensitive food biomarkers are necessary to support dietary intake assessment and link nutritional habits to potential impact on human health. A multistep nutritional intervention study was conducted to suggest novel biomarkers for coffee consumption. (1)H NMR metabolic profiling combined with multivariate data analysis resolved 2-furoylglycine (2-FG) as a novel putative biomarker for coffee consumption. We relatively quantified 2-FG in the urine of coffee drinkers and investigated its origin, metabolism, and excretion kinetics. When searching for its potential precursors, we found different furan derivatives in coffee products, which are known to get metabolized to 2-FG. Maximal urinary excretion of 2-FG occurred 2 h after consumption (p = 0.0002) and returned to baseline after 24 h (p = 0.74). The biomarker was not excreted after consumption of coffee substitutes such as tea and chicory coffee and might therefore be a promising acute biomarker for the detection of coffee consumption in human urine. PMID- 26357999 TI - Bevacizumab in recurrent glioblastoma: open issues. AB - Recurrent glioblastoma represents a challenge in neuro-oncology since the prognosis is poor and current therapeutic options are limited. Bevacizumab has demonstrated activity in this setting in various clinical trials and has been approved by US FDA for the treatment of recurrent glioblastoma. Nevertheless, many issues still exist. In this article, we summarized the principal subjects of controversies that surround bevacizumab and its use in the treatment of recurrent glioblastoma. PMID- 26357998 TI - Infections on the rise: Raoultella spp., clinical and microbiological findings from a retrospective study, 2010-2014. AB - We performed a retrospective analysis of clinical and laboratory data over 5 years in a tertiary centre to assess clinical and microbiological characteristics of patients with Raoultella spp. infection. Raoultella spp. were deemed responsible for clinical infections in 57 patients (R. planticola, n = 32 and R. ornithinolytica, n = 25). The most prevalent diagnoses for R. planticola were cystitis (50%; n = 16) followed by bacteraemia and pneumonia (9.4%; n = 3); for R. ornithinolytica, cystitis (36%; n = 9) followed by pneumonia (24%; n = 6). Immunodeficiency was present in 18 patients (56.3%) with R. planticola and in 16 patients (64%) with R. ornithinolytica infection. Of these, 55.6% and 37.5% had diabetes and 27.8% and 18.% were solid organ transplant recipients, respectively. All isolates were sensitive to third-generation cephalosporins, fluoroquinolones and aminoglycosides. Mortality of infections with R. planticola (n = 5; 15.6%) was higher than for R. ornithinolytica (n = 2; 8.0%), but the difference was not statistically significant. PMID- 26358000 TI - Highly Sensitive and Selective Sensor Chips with Graphene-Oxide Linking Layer. AB - The development of sensing interfaces can significantly improve the performance of biological sensors. Graphene oxide provides a remarkable immobilization platform for surface plasmon resonance (SPR) biosensors due to its excellent optical and biochemical properties. Here, we describe a novel sensor chip for SPR biosensors based on graphene-oxide linking layers. The biosensing assay model was based on a graphene oxide film containing streptavidin. The proposed sensor chip has three times higher sensitivity than the carboxymethylated dextran surface of a commercial sensor chip. Moreover, the demonstrated sensor chips are bioselective with more than 25 times reduced binding for nonspecific interaction and can be used multiple times. We consider the results presented here of importance for any future applications of highly sensitive SPR biosensing. PMID- 26358002 TI - Chronic Exposure of Female Mice to an Environmental Level of Perfluorooctane Sulfonate Suppresses Estrogen Synthesis Through Reduced Histone H3K14 Acetylation of the StAR Promoter Leading to Deficits in Follicular Development and Ovulation. AB - Perfluorooctane sulfonate (PFOS) at a high dose of 10 mg/kg has been reported to affect the neuroendocrine system and exert toxic effects in rodents. The present study examined the influence of chronic exposure to a low-dose of PFOS (0.1 mg/kg/day) on female reproductive endocrine and function. Herein, we show that adult female mice exposed to PFOS by gavage for 4 months (PFOS-mice) exhibited a prolongation of diestrus without signs of toxic effects. The numbers of mature follicles and corpora luteum were significantly reduced in PFOS-mice with increase of atresic follicles. The levels of serum estrogen (E2) and progesterone at proestrus and diestrus were reduced in PFOS-mice. In comparison with controls, PFOS-mice showed a significant decrease in the levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH), and gonadotrophin-releasing hormone, the number of kisspeptin neurons and the level of kiss1 mRNA in anteroventral periventricular nucleus at proestrus but not at diestrus, which could be corrected with the normalization to E2. PFOS-mice did not generate an LH-surge at proestrus, which could be rescued by the application of E2 or kisspeptin-10. Notably, the level of ovarian steroidogenic acute regulatory (StAR) mRNA was decreased in PFOS-mice with the reduction of histone H3K14 acetylation in StAR promoter relative to control mice, whereas the P450scc expression and histone H3K14 acetylation showed no difference between the groups. The present study provides evidence that the chronic exposure to the low-dose of PFOS through selectively reducing histone acetylation of StAR suppresses the biosynthesis of E2 to impair the follicular development and ovulation. PMID- 26358001 TI - Reference Standardization for Mass Spectrometry and High-resolution Metabolomics Applications to Exposome Research. AB - The exposome is the cumulative measure of environmental influences and associated biological responses throughout the lifespan, including exposures from the environment, diet, behavior, and endogenous processes. A major challenge for exposome research lies in the development of robust and affordable analytic procedures to measure the broad range of exposures and associated biologic impacts occurring over a lifetime. Biomonitoring is an established approach to evaluate internal body burden of environmental exposures, but use of biomonitoring for exposome research is often limited by the high costs associated with quantification of individual chemicals. High-resolution metabolomics (HRM) uses ultra-high resolution mass spectrometry with minimal sample preparation to support high-throughput relative quantification of thousands of environmental, dietary, and microbial chemicals. HRM also measures metabolites in most endogenous metabolic pathways, thereby providing simultaneous measurement of biologic responses to environmental exposures. The present research examined quantification strategies to enhance the usefulness of HRM data for cumulative exposome research. The results provide a simple reference standardization protocol in which individual chemical concentrations in unknown samples are estimated by comparison to a concurrently analyzed, pooled reference sample with known chemical concentrations. The approach was tested using blinded analyses of amino acids in human samples and was found to be comparable to independent laboratory results based on surrogate standardization or internal standardization. Quantification was reproducible over a 13-month period and extrapolated to thousands of chemicals. The results show that reference standardization protocol provides an effective strategy that will enhance data collection for cumulative exposome research. In principle, the approach can be extended to other types of mass spectrometry and other analytical methods. PMID- 26358003 TI - High Throughput Measurement of Ca++ Dynamics in Human Stem Cell-Derived Cardiomyocytes by Kinetic Image Cytometery: A Cardiac Risk Assessment Characterization Using a Large Panel of Cardioactive and Inactive Compounds. AB - Human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) are emerging as a powerful in vitro model for cardiac safety assessment which may allow for better identification of compounds with poor arrhythmogenic liability profiles early in the drug discovery process. Here, we describe our examination of the Kinetic Image Cytometer (KIC) system's ability to predict adverse compound effects using hiPS-CMs and a library of 53 compounds, the majority of which are known to be cardioactive compounds, and several negative controls. The KIC provides a high throughput method for analyzing intracellular calcium transients. In the cardiomyocyte, intracellular calcium transients integrate the electrochemical signals of the action potential (AP) with the molecular signaling pathways regulating contraction. Drug-induced alterations in the shape and duration of AP result in changes to the shape and duration of the intracellular calcium transient. By examining calcium transient dynamics in hiPS-CMs, KIC can be used as a phenotypic screen to assess compound effects across multiple ion channel types (MITs), detecting MITs, calcium handling and signaling effects. The results of this blinded study indicate that using hiPS-CMs, KIC is able to accurately detect drug-induced changes in Ca(2+) transient dynamics (ie, duration and beat rate) and therefore, may be useful in predicting drug-induced arrhythmogenic liabilities in early de-risking within the drug discovery phase. PMID- 26358005 TI - Assessment of antiretroviral treatment (ART) care service provision in Tigray Region health centers, North Ethiopia. AB - BACKGROUND: Client satisfaction is a vital component and main concern intertwined with strategic decisions in service provisions. To improve efficiency of services, eliciting the opinion of users about the available services and identifying factors associated with dissatisfaction is very critical. Thus, the main objective of this study was to assess the perceived levels of clients' satisfaction with health services at ART clinic level in health centres of Tigray Region in Ethiopia. METHODS: Cross sectional study was conducted from May to June 2013 in Tigray Region ART clinics. A total of 714 ART care user were included in the study using both purposive and probability sampling technique. Data was collected by using structured questionnaire and the collected data was analysed using Statistical Package for the Social Sciences (SPSS) version 16.0. Crude and Adjusted logistic regression analyses were carried out to identify the associated factors underlying perceived levels of clients' overall satisfaction. Finally, the results were presented with table as well as odds ratio (OR) and 95% confidence interval (CI). RESULTS: A total of 714 study participants were enrolled in this study. An overall satisfaction level of 89.6% was reported by ART care service users. Higher scores of satisfaction of services provisions were reported for courtesy and respect (95.80%) followed by privacy (93.28%). On the other hand, respondents' dissatisfaction was rated 35.32% for toilet cleanliness followed by 26.19% for availability of additional drugs. As for overall satisfaction and associated factors, adjusted logistic regression analyses showed that marital status [AOR = 2.01 (95% CI: 1.11, 3.60)], educational status [AOR = 3.13 (95% CI: 1.15, 8.53)], travel distance to reach health centre [AOR = 3.59 (95% CI: 1.23, 10.50)], toilet cleanliness [AOR = 2.22 (95% CI :1.62, 6.32)], and ART drug availability [AOR = 2.60 (95% CI :1.18, 6.52)] were found to have influence on overall ART service satisfaction status. CONCLUSIONS: This study revealed high level of client satisfaction rate and were associated with preventable and modifiable factors such as marital status, educational status, travel distance to reach health centre, toilet cleanliness and ART drug availability. Therefore, countermeasures such as increasing access to ART service, availing clean toilet and ART drugs may further increase client satisfaction level in the region. PMID- 26358004 TI - Computational analysis of the regulation of Ca(2+) dynamics in rat ventricular myocytes. AB - Force-frequency relationships of isolated cardiac myocytes show complex behaviors that are thought to be specific to both the species and the conditions associated with the experimental preparation. Ca(2+) signaling plays an important role in shaping the force-frequency relationship, and understanding the properties of the force-frequency relationship in vivo requires an understanding of Ca(2+) dynamics under physiologically relevant conditions. Ca(2+) signaling is itself a complicated process that is best understood on a quantitative level via biophysically based computational simulation. Although a large number of models are available in the literature, the models are often a conglomeration of components parameterized to data of incompatible species and/or experimental conditions. In addition, few models account for modulation of Ca(2+) dynamics via beta-adrenergic and calmodulin-dependent protein kinase II (CaMKII) signaling pathways even though they are hypothesized to play an important regulatory role in vivo. Both protein-kinase-A and CaMKII are known to phosphorylate a variety of targets known to be involved in Ca(2+) signaling, but the effects of these pathways on the frequency- and inotrope-dependence of Ca(2+) dynamics are not currently well understood. In order to better understand Ca(2+) dynamics under physiological conditions relevant to rat, a previous computational model is adapted and re-parameterized to a self-consistent dataset obtained under physiological temperature and pacing frequency and updated to include beta adrenergic and CaMKII regulatory pathways. The necessity of specific effector mechanisms of these pathways in capturing inotrope- and frequency-dependence of the data is tested by attempting to fit the data while including and/or excluding those effector components. We find that: (1) beta-adrenergic-mediated phosphorylation of the L-type calcium channel (LCC) (and not of phospholamban (PLB)) is sufficient to explain the inotrope-dependence; and (2) that CaMKII mediated regulation of neither the LCC nor of PLB is required to explain the frequency-dependence of the data. PMID- 26358006 TI - From IgE to clinical trials of allergic rhinitis. AB - The current scientific research is continuously aiming at identifying new therapeutic targets with the purpose of modifying the immune response to allergens. The evolution in immunological methods has led to the identification of immunoglobulin E (IgE) as both a diagnostic biomarker and potential therapeutic target in allergic diseases, such as allergic rhinitis. Allergen immunotherapy has been used for more than 100 years to treat allergic diseases and it is today considered the only disease-modifying treatment capable of inducing a long-lasting immunological and clinical tolerance toward the causal allergen. During the past 20 years, major advances have been made in understanding the molecular and cellular mechanisms of allergen tolerance in humans. Moreover, there has been considerable progress in allergen extract modifications and additions to standard extracts. The recognition that IgE plays a pivotal role in basic regulatory mechanisms of allergic inflammation has recently stimulated research into the therapeutic potential of directly targeting this antibody. Omalizumab, the most advanced humanized anti-IgE monoclonal antibody, is currently approved for the treatment of uncontrolled allergic asthma and chronic spontaneous urticaria. Interesting results also arise from studies in which omalizumab was administered in patients with allergic rhinitis. The aim of this review is to provide an update on current findings on immunological and clinical effects of allergen immunotherapy and anti-IgE therapy, which have been shown to have synergistic modes of action for the treatment of allergic rhinitis. PMID- 26358008 TI - Pseudoaneurysm and aorto-bronchial fistula following balloon dilation of recoarctation. AB - This case report documents the successful surgical repair of an aorto-bronchial fistula and a giant aortic pseudoaneurysm at the proximal anastomosis of a dacron interposition tube graft that was balloon dilated for recurrent coarctation. Balloon dilation for recoarctation of a dacron interposition tube graft may lead to serious complications. PMID- 26358007 TI - Screening for recombinants of Crambe abyssynica after transformation by the pMF1 marker-free vector based on chemical selection and meristematic regeneration. AB - The T-DNA region of pMF1 vector of marker-free system developed by Wageningen UR, has Recombinase R-LBD gene fusion and nptII and codA gene fusion between two recombination sites. After transformation applying dexamethasone (DEX) can activate the recombinase to remove the T-DNA fragment between recombination sites. The recombinant ought to be selected on 5-fluorocytocine (5-FC) because of codA converting 5-FC into 5-fluorouracil the toxic. A PMF1 vector was transformed into hexaploid species Crambe abyssinica. Two independent transformants were chosen for DEX-induced recombination and later 5-FC selection. In contrast to earlier pMF1 experiments, the strategy of stepwise selection based on meristematic regeneration was engaged. After a long period of 5-FC selection, recombinants were obtained successfully, but most of the survivors were wildtype and non-recombinant. The results revealed when applying the PMF1 marker-free system on C. abyssinica, 1) Increasing in the DEX concentration did not correspondingly enhance the success of recombination; 2) both of the DEX-induced recombination and 5-FC negative selection were apparently insufficient which was leading to the extremely high frequency in chimerism occurring for recombinant and non-recombinant cells in tissues; 3) the strategy of stepwise selection based on meristem tissue regeneration was crucial for successfully isolating the recombinant germplasm from the chimera. PMID- 26358009 TI - Oxidative Reactivities of 2-Furylquinolines: Ubiquitous Scaffolds in Common High Throughput Screening Libraries. AB - High-throughput screening (HTS) was employed to discover APOBEC3G inhibitors, and multiple 2-furylquinolines (e.g., 1) were found. Dose-response assays with 1 from the HTS sample, as well as commercial material, yielded similar confirmatory results. Interestingly, freshly synthesized and DMSO-solubilized 1 was inactive. Repeated screening of the DMSO aliquot of synthesized 1 revealed increasing APOBEC3G inhibitory activity with age, suggesting that 1 decomposes into an active inhibitor. Laboratory aging of 1 followed by analysis revealed that 1 undergoes oxidative decomposition in air, resulting from a [4 + 2] cycloaddition between the furan of 1 and (1)O2. The resulting endoperoxide then undergoes additional transformations, highlighted by Baeyer-Villager rearrangements, to deliver lactam, carboxylic acid, and aldehyde products. The endoperoxide also undergoes hydrolytic opening followed by further transformations to a bis-enone. Eight structurally related analogues from HTS libraries were similarly reactive. This study constitutes a cautionary tale to validate 2-furylquinolines for structure and stability prior to chemical optimization campaigns. PMID- 26358010 TI - Enamel erosion and mechanical tooth wear in medieval Icelanders. AB - OBJECTIVES: The Icelandic Sagas are an important source of information on the way of life and diet habits in Iceland and possibly other Nordic countries 1000 years ago. Archaeological human skull material worldwide has revealed extensive tooth wear, with the main cause believed to be coarse diet. From a graveyard near volcano Hekla, 66 skeletons dated from before 1104 were excavated. The purpose of this study was to determine the main causes of tooth wear in Icelanders 1000 years ago. MATERIALS AND METHODS: Forty-nine skulls were available for research. Two methods were used to evaluate tooth wear and seven for age estimation. An attempt was made to determine the main causes of tooth wear in the light of likely diet and beverage consumption according to a computer search on food and drink customs described in the Icelandic Sagas. RESULTS: Tooth wear was extensive in all groups, increasing with age. The highest score was on first molars, with no difference between sexes. It had all the similarities seen in wear from coarse diet. In some instances it had similar characteristics to those seen in erosion in modern Icelanders consuming excessive amounts of soft drinks. According to the Sagas, acidic whey was a daily drink and used for preservation of food in Iceland until recently. CONCLUSIONS: Since acidic whey has considerably high dental erosive potential, it is postulated that consumption of acidic drinks and food, in addition to a coarse and rough diet, played a significant role in the dental wear of ancient Icelanders. PMID- 26358011 TI - General practice clinicians' perspectives on involving and supporting children and adult perpetrators in families experiencing domestic violence and abuse. AB - BACKGROUND: Government and professional guidance encourages general practice clinicians to identify and refer children who experience domestic violence and abuse (DVA) but there is scant understanding of how general practice clinicians currently work with DVA in families. OBJECTIVES: The study explored general practice clinicians' practice with children and their parents experiencing DVA and reflected on the findings in the light of current research and policy guidelines. METHODS: Semi-structured interviews with 54 clinicians (42 GPs and 12 practice nurses/nurse practitioners) were conducted across six sites in England. Data were analysed using current literature and emerging themes. Data presented here concern clinicians' perspectives on engaging with family members when a parent discloses that she is experiencing DVA. RESULTS: When a parent disclosed DVA, clinicians were more likely to consider talking to abusive fathers than talking to children about the abuse. Perspectives varied according to whether consultation opportunities arose, risks, consent and confidentiality. Perceptions of 'patienthood', relationships and competence shaped clinicians' engagement. Perpetrators were seen as competent informers and active service users, with potential for accepting advice and support. Clinicians were more hesitant in talking with children. Where this was considered, children tended to be seen as passive informants, only two GPs described direct and ongoing consultations with children and providing them with access to support. CONCLUSION: Clinicians appear more inclined to engage directly with abusive fathers than children experiencing DVA. Clinician skills and confidence to talk directly with children experiencing DVA, in child sensitive ways, should be developed through appropriate training. PMID- 26358012 TI - Robot-assisted radical prostatectomy in prostate cancer. AB - Since its introduction in the year 2000, robot-assisted radical prostatectomy (RARP) rapidly diffused, and nowadays roughly 70% of all the radical prostatectomies in the USA are performed using this approach. Interestingly, the broad dissemination of RARP occurred in the absence of comprehensive data coming from prospective randomized trials supporting the superiority of RARP versus the conventional open RP (ORP). Only observations originating from retrospective institutional or large population-based cohorts exist with respect to the comparative effectiveness of the two surgical techniques. What we have learned is that, given an adequate learning curve, RARP leads to better perioperative and long-term functional outcomes compared with ORP, without any compromise to cancer control outcomes. That being said, the substantially higher costs associated with the use of robotics cannot be ignored. PMID- 26358013 TI - Asthma in the older adult: presentation, considerations and clinical management. AB - Asthma affects older adults to the same extent as children and adolescents. However, one is led to imagine that asthma prevalence decreases with aging and becomes a rare entity in the elderly. From a clinical perspective, this misconception has nontrivial consequences in that the recognition of the disease is delayed and the treatment postponed. The overall management of asthma in the elderly population is also complicated by specific features that the disease develops in the most advanced ages, and by the difficulties that the physician encounters when approaching the older asthmatic subjects. The current review article aims at describing the specific clinical presentations of asthma in the elderly and highlights the gaps and pitfalls in the diagnostic and therapeutic approaches. Relevant issues with regard to the clinical management of asthma in the elderly are also discussed. PMID- 26358015 TI - Strategic Interventions in the Management of Gestational Diabetes to Reduce Type 2 Diabetes Mellitus in Women in Malaysia. AB - No abstract available. PMID- 26358016 TI - A review of teenage pregnancy research in Malaysia. AB - OBJECTIVE: To summarise the published research on teenage pregnancy in Malaysia, discuss the impact of the findings on clinical practice, and identify gaps in teenage pregnancy research in Malaysia. METHODS: There were 31 articles related to teen pregnancy found after searching a database dedicated to indexing all original clinical research data published in Malaysia from year 2000 to 2014. Twenty-seven articles (including reports from the National Obstetrics Registry) were selected and reviewed on the basis of clinical relevance and future research implications. This literature review has been divided into eight sections: epidemiology, age at first marriage, adolescent fertility rate, unmarried childbearing, risk factors, maternal risks and neonatal outcome, future plan after delivery, and contraceptive use. RESULTS: More than 19,000 births to teenage mothers were recorded each year between 2009 and 2011. Adolescent fertility rates were recorded at 6 births per 1000 women ages 15-19 years in 2013. Many of these births were from unwed pregnancies, which accounted for 1.99% of total deliveries. A majority of young mothers were willing to take care of their baby, although some of them planned to put their baby up for adoption. Risk factors for teenage pregnancy were found to be similar to those published in studies worldwide. CONCLUSION: More research is needed to better understand the issue of teen pregnancy. For the best results, collaborative studies among nationwide hospitals and institutions should be the way forward. PMID- 26358014 TI - PIK3CA mutation analysis in Chinese patients with surgically resected cervical cancer. AB - The aim of this study was to evaluate the clinicopathological and prognostic relevance of PIK3CA mutations in Chinese patients with surgically resected cervical cancer. PIK3CA mutations were screened in 771 cervical cancer specimens using reverse transcription polymerase chain reaction and Sanger sequencing. In total, 13.6% (105 of 771) of patients harbored non-synonymous PIK3CA mutations. Patients harboring PIK3CA mutations were older than patients with wild-type PIK3CA (mean age: 50.7 years vs. 47.0 years, P < 0.01). PIK3CA mutations were more commonly observed in postmenopausal patients than in premenopausal patients (19.6% vs. 10.2%, P < 0.01). PIK3CA mutations were more common in squamous cell carcinomas than in non-squamous cell tumors (15.3% vs 7.3%, of P < 0.01). The 3 year relapse-free survival was 90.2% for PIK3CA mutant patients and 80.9% for PIK3CA wild-type patients (P = 0.03). PIK3CA mutation was confirmed as an independent predictor for better treatment outcome in the multivariate analyses (HR = 0.54, 95% CI: 0.29-0.99, P = 0.048). PIK3CA mutations were significantly associated with less distant metastases (mutant-type: 8/105, wild-type: 98/666, p = 0.048). Thus, patients with mutant PIK3CA had distinct characteristics in age, menopausal status, and histological subtype and have better treatment outcome and less distant metastasis after surgery-based multimodal therapy. PMID- 26358017 TI - Clinical Characteristic of Vertigo in Children. AB - INTRODUCTION: Maternal mortality and morbidity from eclampsia continues to be seen around the globe. Local Key Performance Index on recurrence of eclamptic fits did not meet targets, thus this raised the issue whether the care provided adhered to the standard management for eclampsia. METHODS: This clinical audit was conducted to assess and improve the quality of the service being offered to patient, particularly in managing eclampsia cases. It was conducted according to the audit cycle. It begins with the development of 12 standardized criteria for eclampsia management. First audit was conducted by retrospectively reviewing eclampsia cases from year 2008 till 2012. Strategies for changes were formulated and implemented following the results of the first audit. Second audit was conducted six months after the changes. RESULTS: The overall incidence rate of eclampsia was 9.17 per 10,000 deliveries. A first seizure occurred during the antepartum period in 52.9% of cases (n=27), intrapartum in 24% (n=11) and postpartum in 21% of cases (n=13). Suboptimal care was mainly on delay of activation of Red Alert system and no treatment for uncontrolled blood pressure. Several strategies were implemented, mainly on improving working knowledge of the staffs and reengineering hospital Red Alert system. Positive achievements observed during the second audit, shown by a reduction in the number of patients with recurrence eclamptic fits and perinatal mortality rate. CONCLUSION: Conducting an audit is essential to evaluate local performance against the standardized criteria. Improvement can be achieved with inexpensive solutions and attainable within a short period of time. PMID- 26358018 TI - Cervical Ripening Balloon for Induction of Labour in High Risk Pregnancies. AB - BACKGROUND: The Cervical Ripening Balloon (CRB) is a novel mechanical method for induction of labour (IOL), reducing the risks of hyperstimulation associated with pharmacological methods. However, there remains a paucity of literature on its application in high risk mothers, who have an elevated risk of uterine rupture, namely those with previous scars and grandmultiparity. METHODOLOGY: A retrospective study on IOL using the CRB in women with previous caesarean section or grandmultiparity between January 2014 and March 2015. All cases were identified from the Sarawak General Hospital CRB request registry. Individual admission notes were traced and data extracted using a standardised proforma. RESULTS: The overall success rate of vaginal delivery after IOL was 50%, although this increases to about two-thirds when sub analysis was performed in women with previous tested scars and the unscarred, grandmultiparous woman. There was a significant change in Bishop score prior to insertion and after removal of the CRB. The Bishop score increased by a score of 3.2 (95% CI 2.8-3.6), which was statistically significant (p<0.01) and occurred across both subgroups, not limited to the grandmultipara. There were no cases of hyperstimulation but one case of intrapartum fever and scar dehiscence each (1.4%). Notably, there were two cases of change in lie/presentation after CRB insertion. CONCLUSION: CRB adds to the obstetricians' armamentarium and appears to provide a reasonable alternative for the IOL in women at high risk of uterine rupture. Rates of hyperstimulation, maternal infection and scar dehiscence are low and hence appeals to the user. PMID- 26358019 TI - Reduction of intubation rate during newborn resuscitation after transition from self-inflating bag to T-piece resuscitator. AB - INTRODUCTION: T-piece resuscitator (TPR) has many advantages compared to self inflating bag (SIB). Early Continuous Positive Airway Pressure (CPAP) during newborn resuscitation (NR) with TPR at delivery can reduce intubation rate. METHODS: We speculated that the intubation rate at delivery room was high because SIB had always been used during NR and this can be improved with TPR. Intubation rate of newborn <24 hours of life was deemed high if >50%. An audit was carried out in June 2010 to verify this problem using a check sheet. RESULTS: 25 neonates without major congenital anomalies who required NR with SIB at delivery were included. Intubation rate of babies <24 hours of life when SIB was used was 68%. Post-intervention audit (August to November 2010) on 25 newborns showed that the intubation rate within 24 hours dropped to 8% when TPR was used. Proportion of intubated babies reduced from 48.3% (2008-2009) to 35.1% (2011-2012), odds ratio 0.58 (95% CI 0.49-0.68). Proportion of neonates on CPAP increased from 63.5% (2008-2009) to 81.0% (2011-2012), odds ratio 2.44 (95% CI 2.03-2.93). Mean ventilation days fell to below 4 days after 2010. Since then, all delivery standbys were accompanied by TPR and it was used for all NR regardless of settings. There was decline in intubation rate secondary to early provision of CPAP with TPR during NR. Mean ventilation days, mortality and length of NICU stay were reduced. CONCLUSION: This practice should be adopted by all hospitals in the country to achieve Millennium Development Goal 4 (2/3 decline of under 5 mortality rate) by 2015. PMID- 26358020 TI - Eosinophilic gastroenteritis: Clinical profiles and treatment outcomes, a retrospective study of 18 adult patients in a Singapore Tertiary Hospital. AB - BACKGROUND: Eosinophilic gastroenteritis (EG) can mimic symptoms of common gastrointestinal (GI) disorders but responds well to appropriate treatment. Accurate diagnosis is central to effective management. Data on EG in Southeast Asia is lacking. We aim to describe the clinical profiles and treatment outcomes of adult patients with EG in a Singapore Tertiary Hospital. MATERIALS AND METHODS: This retrospective study involved archival search of patients with GI biopsies that showed eosinophilic infiltration from January 2004 to December 2012. Patients' clinical data from computerised hospital records and clinical notes was reviewed. Diagnostic criteria for EG included presence of GI symptoms with more than 30 eosinophils/high power field on GI biopsies. Patients with secondary causes for eosinophilia were excluded. RESULTS: Eighteen patients with EG were identified (mean age 52 years; male/female: 11/7). Fifteen patients (83%) had peripheral blood eosinophilia. Seven patients (39%) had atopic conditions. Most common symptoms were diarrhoea and abdominal pain. Small intestine was the most common site involved. Endoscopic finding was non-specific. Ten patients were treated with corticosteroids (nine prednisolone, one budesonide): eight patients (89%) responded clinically to prednisolone but four patients (50%) relapsed following tapering-off of prednisolone and required maintenance dose. One patient each responded to diet elimination and montelukast respectively. Half of the remaining six patients who were treated with proton-pump inhibitors, antispasmodic or antidiarrheal agents still remained symptomatic. CONCLUSION: Prednisolone is an effective treatment though relapses are common. Small intestine is most commonly involved. EG should be considered in the evaluation of unexplained chronic recurrent GI symptoms. PMID- 26358021 TI - Accuracy of ultrasound versus computed tomography urogram in detecting urinary tract calculi. AB - AIM: To determine the (i) sensitivity and specificity of ultrasound (USG) in the detection of urinary tract calculi, (ii) size of renal calculi detected on USG, and (iii) size of renal calculi not seen on USG but detected on computed tomography urogram (CTU). METHODS: A total of 201 patients' USG and CTU were compared retrospectively for the presence of calculi. Sensitivity, specificity, accuracy, positive predictive value and negative predictive value of USG were calculated with CTU as the gold standard. RESULTS: From the 201 sets of data collected, 59 calculi were detected on both USG and CTU. The sensitivity and specificity of renal calculi detection on USG were 53% and 85% respectively. The mean size of the renal calculus detected on USG was 7.6 mm +/- 4.1 mm and the mean size of the renal calculus not visualised on USG but detected on CTU was 4 mm +/- 2.4 mm. The sensitivity and specificity of ureteric calculi detection on USG were 12% and 97% respectively. The sensitivity and specificity of urinary bladder calculi detection on USG were 20% and 100% respectively. CONCLUSION: This study showed that the accuracy of US in detecting renal, ureteric and urinary bladder calculi were 67%, 80% and 98% respectively. PMID- 26358022 TI - Validation of the Malay version of the Amsterdam Preoperative Anxiety and Information Scale (APAIS). AB - BACKGROUND: Preoperative anxiety is a significant problem worldwide that may affect patients' surgical outcome. By using a simple and reliable tool such as the Amsterdam Preoperative Anxiety and Information Scale (APAIS), anaesthesiologists would be able to assess preoperative anxiety adequately and accurately. OBJECTIVE: The purpose of this study was to develop and validate the Malay version of APAIS (Malay-APAIS), and assess the factors associated with higher anxiety scores. METHODS: The authors performed forward and backward translation of APAIS into Malay and then tested on 200 patients in the anaesthetic clinic of University Malaya Medical Centre. Psychometric analysis was performed with factor analysis, internal consistency and correlation with Spielberger's State-Trait Anxiety Inventory (STAI-state). RESULTS: A good correlation was shown with STAI-state (r = 0.59). Anxiety and need for information both emerged with high internal consistency (Cronbach's alpha 0.93 and 0.90 respectively). Female gender, surgery with a higher risk and need for information were found to be associated with higher anxiety scores. On the other hand, previous experience with surgery had lower need for information. CONCLUSION: The Malay-APAIS is a valid and reliable tool for the assessment of patients' preoperative anxiety and their need for information. By understanding and measuring patient's concerns objectively, the perioperative management will improve to a much higher standard of care. PMID- 26358023 TI - Severe hypertriglyceridemia in a nondiabetic treated with low dose insulin infusion. AB - We report a case of a 54-year-old man with severe HTG which did not respond to conventional anti lipid therapies. He was treated with intravenous insulin and concurrent dextrose infusions which led to a dramatic reduction in serum triglyceride levels. PMID- 26358024 TI - Patients that benefit from buprenorphine-naloxone on medically assisted treatment for opioid dependence in Malaysia. AB - INTRODUCTION: Opioid dependence is recorded as the most common drug of abuse in Malaysia. Currently, the preferred substitution therapy for most Government treatment centres is methadone used as substitution therapy for opioid dependence. There are, however patients who may benefit from being on the combined buprenorphine-naloxone formulation as substitution therapy instead. We discuss six cases of opioid dependence of varied backgrounds that were treated with buprenorphinenaloxone therapy and their outcomes. DISCUSSION: All of the reported patients improved after the induction of buprenorphine- naloxone. Two of the cases highlighted the transfer of patients on methadone to buprenorphine naloxone due to the adverse effect and interactions of methadone with other medications. During the transfer there were no major adverse reactions noted, and patients were safely able to continue with the maintenance therapy of buprenorphine- naloxone. CONCLUSION: Buprenorphine-naloxone is a safe and effective drug substitution therapy for opioid dependence. It has fewer interactions with other medications, and has similar efficacy to methadone. Being a partial agonist, it has a less sedating effect making patients more functional. PMID- 26358025 TI - Radiologically occult hepatocellular carcinoma in a cirrhotic liver presenting with bilateral adrenal metastases. AB - Although it is common to have extra-hepatic metastasis of hepatocellular carcinoma (HCC) at the time of presentation, it is extremely rare to have extra hepatic metastatic HCC without a detectable primary in the liver. We report a unique case in which a patient presented with bilateral large adrenal masses which were subsequently proven to be metastases from HCC. However, there was no tumour seen in the liver on imaging. PMID- 26358026 TI - Isolated fallopian tube torsion in prepubertal females. AB - Isolated fallopian tube torsion is an uncommon diagnosis. It is particularly rare in the paediatric and post-menopausal age groups. It lacks pathognomonic symptoms, signs and imaging findings, yet each of these diagnostic steps plays a crucial role in early diagnosis. We describe two cases of isolated fallopian tube torsion in prepubertal females. PMID- 26358027 TI - Enlarged parietal foramina presenting as scalp swelling in an infant. AB - "Enlarged parietal foramina" is a congenital malformation with autosomal dominant inheritance. The condition is usually self-limiting and doesn't require any treatment. However, it may also be associated with encephalocele, vascular anomalies or may be a part of syndrome. We present a case of enlarged parietal foramina in a child and discuss its imaging findings and the associated intracranial vascular malformations. PMID- 26358028 TI - Purple urine bag syndrome: Case report from a nursing home resident with a false alarm of urosepsis. AB - Purple urine bag syndrome (PUBS), as the name implies produces purplish discoloration of the urine. It is commonly observed among elderly women with constipation, and individuals with long term catheter in the setting of urinary tract infection (UTI). From the literature research, there were no publications on PUBS in Malaysia; however we believe that it is underreported. We present a unique case of this rare condition occurring in a 68-year-old man, a nursing home resident on long term urinary catheter. The urine cleared after hydration, antibiotic therapy and replacement of the catheter. PMID- 26358029 TI - Medical student stress: an elective course as a possibility of help. AB - BACKGROUND: The frequently observed stress of medical students worldwide leads them to have psychic suffering often leading to illness. Minor psychic disorders such as anxiety, depression and burnout, have a higher prevalence in these students than in the rest of random population. Different initiatives were tried to minimize the deleterious effects of the medical course and this article aims at showing the repercussions of a elective course that and was proposed as a possibility to help the students. METHODS: A qualitative case study took place in a public Brazilian university as an elective discipline offered to medical students in 2013, offering coping strategies for professional stress. The data was collected through a semi-structured individual questionnaire that was anonymous, and given to students on the last day of the course, with 18 Likert scale questions about personal and behavioural changes observed after taking the course. Objective questions were asked about their perception of stress at the beginning and at the end of the course: the use of the coping strategies taught and the perception of the utility of the content. In addition, one open-ended question was asked about the meaning of the discipline to the students. The quantitative data was analysed with descriptive simple statistics and the qualitative with the support of the WebQDA software. The research project was approved by the ethics committee of the institution. RESULTS: The results showed that the course contributed positively to the students' academic life: 67% reported less symptoms of stress at the end of the course; 76% adopted new coping strategies; and 90% considered that this learning activity was useful for identifying stressors and sharing them with colleagues. CONCLUSIONS: The elective course produced benefits to the students, representing theoretical-practical learning and an opportunity for reflection and self-knowledge, which caused psychological, behavioural and lifestyle changes. It is recommended that further studies on this theme should be conducted. PMID- 26358030 TI - Older Women Fleeing Violence and Abuse in Canada: Bringing Together Separate Spheres of Practice. AB - Supporting older women fleeing violence is challenging work that demands knowledge of both elder abuse and violence against women. Yet, these two communities of practice operate largely as separate spheres. Efforts to better collaborate services and develop alternative approaches for supporting older women fleeing violence are needed. PMID- 26358031 TI - The effect of high medical expenses on household income in South Korea: a longitudinal study using propensity score matching. AB - BACKGROUND: Almost 97% of the Korean population is covered by National Health Insurance and are entitled to receive the same level of insurance benefits, regardless of how much each enrollee contributes to the system. However, the percentage of out-of-pocket payments is still high. This study examines whether the incurrence of high medical expenses affects household income. METHODS: We use the Korea Welfare Panel and select 4,962 households to measure repeatedly over 5 years. Using propensity score matching, we set households with medical expenses of three times the annual average as "occurrence households" while "non occurrence households" are those below the cut-off but with all other factors, such as income, held constant. We analyze whether the income of occurrence households differs significantly from the comparison group using a linear mixed effect model. RESULTS: After the occurrence of high medical expenditure, occurrence households (n = 825) had US$ 1,737 less income than non-occurrence households. In addition, the income of households (n = 200) that incurred high medical costs repeatedly for 2 years was US$ 3,598 lower than the non-occurrence group. CONCLUSIONS: Although it is important for the government to focus on medical assistance for households that have medical expense burdens, it needs to consider providing income indemnity insurance to protect them. PMID- 26358032 TI - Live 3D image overlay for arterial duct closure with Amplatzer Duct Occluder II additional size. AB - Despite several reports describing echocardiography for the guidance of ductal closure, two-dimensional angiography remains the mainstay imaging tool; three dimensional rotational angiography has the potential to overcome some of the drawbacks of standard angiography, and reconstructed image overlay provides reliable guidance for device placement. We describe arterial duct closure solely from venous approach guided by live three-dimensional image overlay. PMID- 26358033 TI - Effect of Diffusion on Resonance Energy Transfer Rate Distributions: Implications for Distance Measurements. AB - Intrinsically disordered protein regions and many other biopolymers lack the three-dimensional structure that could be determined by X-ray crystallography or NMR, which encourages the application of alternative experimental methods. Time resolved resonance energy transfer data are often used to measure distances between two fluorophores attached to a flexible biopolymer. This is complicated by the rotational and translational diffusion of the fluorophores and by nonmonoexponential donor decay in the absence of the acceptor. Equation I(DA)(t) = I(D)(t).F(t) is derived here, which is applicable regardless of whether I(D)(t) is monoexponential. I(D)(t) and I(DA)(t) are the delta-excitation donor emission decays in the absence and in the presence of the acceptor; F(t) contains information about energy transfer, donor-acceptor distance distribution, and diffusion dynamics. It is shown that in the absence of rotational and translational diffusion, F(t) is a continuous distribution of exponentials, whereas in the presence of rotational and translational diffusion, F(t) is a sum of discrete exponentials. For each case it is shown how F(t) is related to the distance distribution. Experimental data obtained with a flexible tetradecapeptide in aqueous solution clearly demonstrate that F(t) is a sum of discrete exponential terms. A partial differential equation describing resonance energy transfer in the presence of both rotational and translational diffusion of the donor and acceptor tethered to the ends of a semiflexible chain is solved in this work using a combination of analytical and numerical methods; the solution is used to fit time-resolved emission of the donor, which makes it possible to determine the model parameters: contour length, persistence length, and the end to-end translational diffusion coefficient. PMID- 26358034 TI - EALab (Eye Activity Lab): a MATLAB Toolbox for Variable Extraction, Multivariate Analysis and Classification of Eye-Movement Data. AB - Recent advances in the reliability of the eye-tracking methodology as well as the increasing availability of affordable non-intrusive technology have opened the door to new research opportunities in a variety of areas and applications. This has raised increasing interest within disciplines such as medicine, business and education for analysing human perceptual and psychological processes based on eye tracking data. However, most of the currently available software requires programming skills and focuses on the analysis of a limited set of eye-movement measures (e.g., saccades and fixations), thus excluding other measures of interest to the classification of a determined state or condition. This paper describes 'EALab', a MATLAB toolbox aimed at easing the extraction, multivariate analysis and classification stages of eye-activity data collected from commercial and independent eye trackers. The processing implemented in this toolbox enables to evaluate variables extracted from a wide range of measures including saccades, fixations, blinks, pupil diameter and glissades. Using EALab does not require any programming and the analysis can be performed through a user-friendly graphical user interface (GUI) consisting of three processing modules: 1) eye-activity measure extraction interface, 2) variable selection and analysis interface, and 3) classification interface. PMID- 26358035 TI - Trigger tool versus verbal inventory to detect surgical complications. AB - PURPOSE: Traditionally, registering complications after surgery is based on voluntary reporting or incident reports. These methods may fail to detect the total number of complications. A trigger tool was developed to detect complications in hospitalized surgical patients. In this diagnostic study, we compared its sensitivity and specificity with the verbal inventory by surgical staff and residents. METHODS: A set of 31 potential triggers was chosen based on a systematic review and availability in hospital databases. The trigger tool was developed using multivariable regression and Receiver Operating Characteristic (ROC) analyses. A reference standard consisted of 300 patients, 150 with and 150 without complications. Sensitivity and specificity of the trigger tool and verbal inventory were determined. RESULTS: The final trigger tool consisted of nine triggers. Sensitivities of the trigger tool and verbal inventory were 70.7 vs. 78.7%, respectively, while specificities were 70.0 vs. 100.0%, respectively. Sensitivity values to detect major complications were 97.2 vs. 80.6%, respectively. CONCLUSIONS: The proposed customized trigger tool for a university hospital to detect surgical patients with complications appeared as accurate as a verbal inventory and even more accurate to detect major complications. PMID- 26358036 TI - The hydrodynamic basis of the vacuum cleaner effect in continuous-flow PCNL instruments: an empiric approach and mathematical model. AB - PURPOSE: Passive removal of stone fragments in the irrigation stream is one of the characteristics in continuous-flow PCNL instruments. So far the physical principle of this so-called vacuum cleaner effect has not been fully understood yet. The aim of the study was to empirically prove the existence of the vacuum cleaner effect and to develop a physical hypothesis and generate a mathematical model for this phenomenon. METHODS: In an empiric approach, common low-pressure PCNL instruments and conventional PCNL sheaths were tested using an in vitro model. Flow characteristics were visualized by coloring of irrigation fluid. Influence of irrigation pressure, sheath diameter, sheath design, nephroscope design and position of the nephroscope was assessed. Experiments were digitally recorded for further slow-motion analysis to deduce a physical model. RESULTS: In each tested nephroscope design, we could observe the vacuum cleaner effect. Increase in irrigation pressure and reduction in cross section of sheath sustained the effect. Slow-motion analysis of colored flow revealed a synergism of two effects causing suction and transportation of the stone. For the first time, our model showed a flow reversal in the sheath as an integral part of the origin of the stone transportation during vacuum cleaner effect. The application of Bernoulli's equation provided the explanation of these effects and confirmed our experimental results. CONCLUSIONS: We widen the understanding of PCNL with a conclusive physical model, which explains fluid mechanics of the vacuum cleaner effect. PMID- 26358037 TI - Understanding the discriminant factors that influence the adoption and use of clinical communities of practice: the ECOPIH case. AB - BACKGROUND: The aim of the study presented in this article is to analyse the discriminant factors that have an influence on the use of communities of practice by primary and specialist healthcare professionals (physicians and nurses) for information sharing. Obtaining evidence from an ex-ante analysis to determine what factors explain healthcare professionals' clinical community of practice use allows aspects of its use to be identified. METHODS: A theoretical model based on a modified technology acceptance model was used as the analysis tool, and a discriminant analysis was performed. An ad-hoc questionnaire was designed and sent to a study population of 357 professionals from the Badalona-Sant Adria de Besos Primary Care Service in Catalonia, Spain, which includes nine primary care centres and three specialist care centres. The study sample was formed by the 166 healthcare professionals who responded. RESULTS: The results revealed three main drivers for engagement in a CoP: First, for the whole sample, perceived usefulness for reducing costs associated with clinical practice was the factor with the greatest discriminant power that distinguished between users and non users, followed by perceived usefulness for improving clinical practice quality, and lastly habitual social media website and application use. Turning to the two sub-samples of healthcare professions (physicians and nurses, respectively), we saw that the usefulness stemming from community of practice use changed. There were differences in the levels of motivation of healthcare professionals with regards to their engagement with CoP. While perceived usefulness for reducing costs associated with clinical practice was the main factor for the physicians, perceived usefulness of the Web 2.0 platform use for communication for improving clinical practice quality and perceived ease of use were the main factors for the nurses. CONCLUSIONS: In the context of communities of practice, the perception of usefulness of Web 2.0 platform use for communication is determined by organisational, technological and social factors. Specifically, the position that professionals have within the healthcare structure and particularly the closer healthcare professionals' activity is to patients and their professional experience of using social networks and ICTs are crucial to explaining the use of such platforms. Public policies promoting Web 2.0 platform use for communication should therefore go beyond the purely technological dimension and consider other professional and social determinants. PMID- 26358038 TI - Ginsenoside Rd Improves Learning and Memory Ability in APP Transgenic Mice. AB - Alzheimer's disease (AD) is a complicated neurodegenerative disease which causes memory loss and dementia. Many researchers have revealed the vital roles of beta amyloid proteins (Abeta) in the proceeds of AD. Abeta deposition in AD patients' brains might function as immune stimulus, and inflammation is believed to play an important role in AD pathologically. We experimentally used amyloid beta-protein precursor (APP) transgenic (Tg) mice in this study to further clarify the neuroprotective effects of ginsenoside Rd on AD and its possible mechanisms. It was found that Rd could improve learning and memory ability in APP Tg mice, probably through inhibiting the transcription activity of NFkappaB. With the activation of the NFkappaB pathway being suppressed, the reduction of pro inflammatory cytokines and the generation of protective factors had been increased ultimately. In conclusion, Rd had a neuroprotective effect on APP Tg mice, and it can be used as an alternative drug therapy in AD patients for their memory dysfunction. PMID- 26358039 TI - Low-Dose Endothelial Monocyte-Activating Polypeptide-II Induces Blood-Tumor Barrier Opening Via the cAMP/PKA/Rac1 Pathway. AB - Previous studies have demonstrated that low-dose endothelial monocyte-activating polypeptide-II (EMAP-II) induces blood-tumor barrier (BTB) hyperpermeability via both paracellular and transcellular pathways. In a recent study, we revealed that cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)-dependent signaling pathway is involved in EMAP-II-induced BTB hyperpermeability. This study further investigated the exact mechanisms through which the cAMP/PKA-dependent signaling pathway affects EMAP-II-induced BTB hyperpermeability. In an in vitro BTB model, low-dose EMAP-II (0.05 nM) induced a significant decrease in Rac1 activity in rat brain microvascular endothelial cells (RBMECs). Pretreatment with forskolin to elevate intracellular cAMP concentration completely blocked EMAP-II-induced inactivation of Rac1. Besides, pretreatment with 6Bnz-cAMP to activate PKA partially attenuated EMAP-II-induced Rac1 inactivation. Moreover, 6Bnz-cAMP pretreatment significantly diminished EMAP-II-induced changes in BTB permeability, myosin light chain (MLC) phosphorylation, expression and distribution of ZO-1, and actin cytoskeleton arrangement in RBMECs. These effects of 6Bnz-cAMP were completely blocked in the presence of NSC-23766 (the specific inhibitor of Rac1). In conclusion, this study demonstrates that low-dose EMAP-II induces BTB hyperpermeability via the cAMP/PKA/Rac1 signaling pathway. PMID- 26358040 TI - Prasiolin, a new UV-sunscreen compound in the terrestrial green macroalga Prasiola calophylla (Carmichael ex Greville) Kutzing (Trebouxiophyceae, Chlorophyta). AB - MAIN CONCLUSION: We introduced a novel combination of chromatographic techniques for the purification and analysis of a new UV-sunscreen mycosporine-like amino acid (MAA) in the terrestrial green alga Prasiola calophylla. Prasiola calophylla (Carmichael ex Greville) Kutzing (Trebouxiophyceae, Chlorophyta) is a typical member of terrestrial algal communities in temperate Europe, where it regularly experiences various stress conditions including strong diurnal and seasonal fluctuations in ultraviolet radiation (UVR). As a photoprotective mechanism Prasiola species and other related Trebouxiophycean taxa synthesize a mycosporine like amino acid (MAA) as natural sunscreen whose chemical structure was unknown so far. In the present study a new methodological approach is described for the isolation, purification and structural elucidation of this novel sunscreen in P. calophylla. The new compound exhibits an absorption maximum at 324 nm (in the short ultraviolet-A), a molecular weight of 333 and a molecular extinction coefficient of 12.393 M(-1) cm(-1), and could be identified as N-[5,6 hydroxy 5(hydroxymethyl)-2-methoxy-3-oxo-1-cycohexen-1-yl] glutamic acid using one- and two-dimensional (1)H and (13)C-NMR spectroscopy. As trivial name for this novel MAA we suggest 'prasiolin'. The ecologically essential function of prasiolin for UVR-protection in terrestrial algae of the Trebouxiophyceae is discussed. PMID- 26358041 TI - Rapid and step-wise eye growth in molting diving beetle larvae. AB - However complex a visual system is, the size (and growth rate) of all its components-lens, retina and nervous system-must be precisely tuned to each other for the system to be functional. As organisms grow, their eyes must be able to achieve and maintain emmetropia, a state in which photoreceptors receive sharp images of objects that are at infinity. While there has been ample research into how vertebrates coordinate eyes growth, this has never been addressed in arthropods with camera eyes, which tend to grow dramatically and typically in a step-wise manner with each molt (ecdysis). Here, we used histological and optical methods to measure how the larval eyes of Sunburst Diving Beetles (Thermonectus marmoratus, Coleoptera, Dytiscidae) grow, and how well optical and morphological parameters match, during the dramatic growth that occurs between two consecutive larval stages. We find that the eye tubes of the principal eyes of T. marmoratus grow substantially around molt, with the vitreous-like crystalline cone contributing the most to the overall growth. Lenses also reform relatively quickly, undergoing a period of dysfunction and then regaining the ability to project sharp images onto the retina around 8 h post-molt. PMID- 26358042 TI - Abolition of mitochondrial substrate-level phosphorylation by itaconic acid produced by LPS-induced Irg1 expression in cells of murine macrophage lineage. AB - Itaconate is a nonamino organic acid exhibiting antimicrobial effects. It has been recently identified in cells of macrophage lineage as a product of an enzyme encoded by immunoresponsive gene 1 (Irg1), acting on the citric acid cycle intermediate cis-aconitate. In mitochondria, itaconate can be converted by succinate-coenzyme A (CoA) ligase to itaconyl-CoA at the expense of ATP (or GTP), and is also a weak competitive inhibitor of complex II. Here, we investigated specific bioenergetic effects of increased itaconate production mediated by LPS induced stimulation of Irg1 in murine bone marrow-derived macrophages (BMDM) and RAW-264.7 cells. In rotenone-treated macrophage cells, stimulation by LPS led to impairment in substrate-level phosphorylation (SLP) of in situ mitochondria, deduced by a reversal in the directionality of the adenine nucleotide translocase operation. In RAW-264.7 cells, the LPS-induced impairment in SLP was reversed by short-interfering RNA(siRNA)-but not scrambled siRNA-treatment directed against Irg1. LPS dose-dependently inhibited oxygen consumption rates (61-91%) and elevated glycolysis rates (>21%) in BMDM but not RAW-264.7 cells, studied under various metabolic conditions. In isolated mouse liver mitochondria treated with rotenone, itaconate dose-dependently (0.5-2 mM) reversed the operation of adenine nucleotide translocase, implying impairment in SLP, an effect that was partially mimicked by malonate. However, malonate yielded greater ADP-induced depolarizations (3-19%) than itaconate. We postulate that itaconate abolishes SLP due to 1) a "CoA trap" in the form of itaconyl-CoA that negatively affects the upstream supply of succinyl-CoA from the alpha-ketoglutarate dehydrogenase complex; 2) depletion of ATP (or GTP), which are required for the thioesterification by succinate-CoA ligase; and 3) inhibition of complex II leading to a buildup of succinate which shifts succinate-CoA ligase equilibrium toward ATP (or GTP) utilization. Our results support the notion that Irg1 expressing cells of macrophage lineage lose the capacity of mitochondrial SLP for producing itaconate during mounting of an immune defense. PMID- 26358043 TI - Virus tolerance and recovery from viral induced-symptoms in plants are associated with transcriptome reprograming. AB - Plant recovery from viral infection is characterized by initial severe systemic symptoms which progressively decrease, leading to reduced symptoms or symptomless leaves at the apices. A key feature to plant recovery from invading nucleic acids such as viruses is the degree of the host's initial basal immunity response. We review current links between RNA silencing, recovery and tolerance, and present a model in which, in addition to regulation of resistance (R) and other defence related genes by RNA silencing, viral infections incite perturbations of the host physiological state that trigger reprogramming of host responses to by-pass severe symptom development, leading to partial or complete recovery. Recovery, in particular in perennial hosts, may trigger tolerance or virus accommodation. We discuss evidence suggesting that plant viruses can avoid total clearance but persistently replicate at low levels, thereby modulating the host transcriptome response which minimizes fitness cost and triggers recovery from viral-symptoms. In some cases a susceptible host may fail to recover from initial viral systemic symptoms, yet, accommodates the persistent virus throughout the life span, a phenomenon herein referred to as non-recovery accommodation, which differs from tolerance in that there is no distinct recovery phase, and differs from susceptibility in that the host is not killed. Recent advances in plant recovery from virus-induced symptoms involving host transcriptome reprogramming are discussed. PMID- 26358045 TI - Association between organizational climate and perceptions and use of an innovation in Swedish primary health care: a prospective study of an implementation. AB - BACKGROUND: There is a need for new knowledge regarding determinants of a successful implementation of new methods in health care. The role of a receptive context for change to support effective diffusion has been underlined, and could be studied by assessing the organizational climate. The aim of this study was to assess the association between organizational climate when a computer-based lifestyle intervention tool (CLT) was introduced in primary health care (PHC) and the implementation outcome in terms of how the tool was perceived and used after 2 years. METHODS: The CLT was offered to 32 PHC units in Sweden, of which 22 units agreed to participate in the study. Before the introduction of the CLT, the creative climate at each participating unit was assessed. After 24 months, a follow-up questionnaire was distributed to the staff to assess how the CLT was perceived and how it was used. A question on the perceived need for the CLT was also included. RESULTS: The units were divided into three groups according to the creative climate: high, medium and low. The main finding was that the units identified as having a positive creative climate demonstrated more frequent use and more positive perceptions regarding the new tool than those with the least positive creative climate. More positive perceptions were seen at both individual and unit levels. CONCLUSIONS: According to the results from this study there is an association between organizational climate at baseline and implementation outcome after 2 years when a tool for lifestyle intervention is introduced in PHC in Sweden. Further studies are needed before measurement of organizational climate at baseline can be recommended in order to predict implementation outcome. PMID- 26358046 TI - Erratum to: Pick of the Year 2014. PMID- 26358044 TI - Molecular dissection of a rice microtubule-associated RING finger protein and its potential role in salt tolerance in Arabidopsis. AB - Although a number of RING E3 ligases in plants have been demonstrated to play key roles in a wide range of abiotic stresses, relatively few studies have detailed how RING E3 ligases exert their cellular actions. We describe Oryza sativa RING finger protein with microtubule-targeting domain 1 (OsRMT1), a functional RING E3 ligase that is likely involved in a salt tolerance mechanism. Functional characterization revealed that OsRMT1 undergoes homodimer formation and subsequently autoubiquitination-mediated protein degradation under normal conditions. By contrast, OsRMT1 is predominantly found in the nucleus and microtubules and its degradation is inhibited under salt stress. Domain dissection of OsRMT1 indicates that the N-terminal domain is required for microtubule targeting. Bimolecular fluorescence complementation analysis and degradation assay revealed that OsRMT1-interacted proteins localized in various organelles were degraded via the ubiquitin (Ub)/26S proteasome-dependent pathway. Interestingly, when OsRMT1 and its target proteins were co-expressed in N. benthamiana leaves, the protein-protein interactions appeared to take place mainly in the microtubules. Overexpression of OsRMT1 in Arabidopsis resulted in increased tolerance to salt stress. Our findings suggest that the abundance of microtubule-associated OsRMT1 is strictly regulated, and OsRMT1 may play a relevant role in salt stress response by modulating levels of its target proteins. PMID- 26358047 TI - An interview with Julie Vose: where is oncology heading? AB - Julie M Vose speaks to Gemma Westcott, Commissioning Editor: Julie M Vose, is the Neumann M and Mildred E Harris Professor and Chief in the Division of Oncology/Hematology at the University of Nebraska Medical Center in Omaha (NE, USA). She received her medical degree, completed her residency in Internal Medicine, served as Chief Resident and completed a Fellowship in Hematology/Oncology at the University of Nebraska Medical Center. She also completed a sabbatical at Stanford University (CA, USA) and an MBA in Health Administration through the University of Colorado Business School (CO, USA). She has focused her career on translational research for improvement in the therapy of non-Hodgkin's lymphoma (NHL) and Hodgkin lymphoma by developing a focused translational research program, evaluating novel therapies such as radiolabeled monoclonal antibodies, idiotype vaccine therapies, pathway-directed agents and stem cell transplantation. She has been recognized for her NHL research on a national and international level through research awards and invited lectureships worldwide. In addition, her funding record and publications in NHL therapy and transplantation research have added substantially to the research and knowledge base for the therapy of lymphoma. She is currently the 2015-2016 President of the American Society of Clinical Oncology. PMID- 26358048 TI - Root-soil air gap and resistance to water flow at the soil-root interface of Robinia pseudoacacia. AB - During periods of water deficit, growing roots may shrink, retaining only partial contact with the soil. In this study, known mathematical models were used to calculate the root-soil air gap and water flow resistance at the soil-root interface, respectively, of Robinia pseudoacacia L. under different water conditions. Using a digital camera, the root-soil air gap of R. pseudoacacia was investigated in a root growth chamber; this root-soil air gap and the model inferred water flow resistance at the soil-root interface were compared with predictions based on a separate outdoor experiment. The results indicated progressively greater root shrinkage and loss of root-soil contact with decreasing soil water potential. The average widths of the root-soil air gap for R. pseudoacacia in open fields and in the root growth chamber were 0.24 and 0.39 mm, respectively. The resistance to water flow at the soil-root interface in both environments increased with decreasing soil water potential. Stepwise regression analysis demonstrated that soil water potential and soil temperature were the best predictors of variation in the root-soil air gap. A combination of soil water potential, soil temperature, root-air water potential difference and soil root water potential difference best predicted the resistance to water flow at the soil-root interface. PMID- 26358049 TI - Nitrogen and phosphorus additions alter nutrient dynamics but not resorption efficiencies of Chinese fir leaves and twigs differing in age. AB - It is unclear how or even if phosphorus (P) input alters the influence of nitrogen (N) deposition in a forest. In theory, nutrients in leaves and twigs differing in age may show different responses to elevated nutrient input. To test this possibility, we selected Chinese fir (Cunninghamia lanceolata) for a series of N and P addition experiments using treatments of +N1 - P (50 kg N ha(-1) year( 1)), +N2 - P (100 kg N ha(-1) year(-1)), -N + P (50 kg P ha(-1) year(-1)), +N1 + P, +N2 + P and -N - P (without N and P addition). Soil samples were analyzed for mineral N and available P concentrations. Leaves and twigs in summer and their litters in winter were classified as and sorted into young and old components to measure N and P concentrations. Soil mineral N and available P increased with N and P additions, respectively. Nitrogen addition increased leaf and twig N concentrations in the second year, but not in the first year; P addition increased leaf and twig P concentrations in both years and enhanced young but not old leaf and twig N accumulations. Nitrogen and P resorption proficiencies in litters increased in response to N and P additions, but N and P resorption efficiencies were not significantly altered. Nitrogen resorption efficiency was generally higher in leaves than in twigs and in young vs old leaves and twigs. Phosphorus resorption efficiency showed a minimal variation from 26.6 to 47.0%. Therefore, P input intensified leaf and twig N enrichment with N addition, leaf and twig nutrients were both gradually resorbed with aging, and organ and age effects depended on the extent of nutrient limitation. PMID- 26358050 TI - Trees harvesting the clouds: fog nets threatened by climate change. PMID- 26358051 TI - Carbon isotope composition of latex does not reflect temporal variations of photosynthetic carbon isotope discrimination in rubber trees (Hevea brasiliensis). AB - Latex, the cytoplasm of laticiferous cells localized in the inner bark of rubber trees (Hevea brasiliensis Mull. Arg.), is collected by tapping the bark. Following tapping, latex flows out of the trunk and is regenerated, whereas in untapped trees, there is no natural exudation. It is still unknown whether the carbohydrates used for latex regeneration in tapped trees is coming from recent photosynthates or from stored carbohydrates, and in the former case, it is expected that latex carbon isotope composition of tapped trees will vary seasonally, whereas latex isotope composition of untapped trees will be more stable. Temporal variations of carbon isotope composition of trunk latex (delta(13)C-L), leaf soluble compounds (delta(13)C-S) and bulk leaf material (delta(13)C-B) collected from tapped and untapped 20-year-old trees were compared. A marked difference in delta(13)C-L was observed between tapped and untapped trees whatever the season. Trunk latex from tapped trees was more depleted (1.60/00 on average) with more variable delta(13)C values than those of untapped trees. delta(13)C-L was higher and more stable across seasons than delta(13)C-S and delta(13)C-B, with a maximum seasonal difference of 0.70/00 for tapped trees and 0.30/00 for untapped trees. delta(13)C-B was lower in tapped than in untapped trees, increasing from August (middle of the rainy season) to April (end of the dry season). Differences in delta(13)C-L and delta(13)C-B between tapped and untapped trees indicated that tapping affects the metabolism of both laticiferous cells and leaves. The lack of correlation between delta(13)C L and delta(13)C-S suggests that recent photosynthates are mixed in the large pool of stored carbohydrates that are involved in latex regeneration after tapping. PMID- 26358052 TI - Improved memory for error feedback. AB - Surprising feedback in a general knowledge test leads to an improvement in memory for both the surface features and the content of the feedback (Psychon Bull Rev 16:88-92, 2009). Based on the idea that in cognitive tasks, error is surprising (the orienting account, Cognition 111:275-279, 2009), we tested whether error feedback would be better remembered than correct feedback. Colored words were presented as feedback signals in a flanker task, where the color indicated the accuracy. Subsequently, these words were again presented during a recognition task (Experiment 1) or a lexical decision task (Experiments 2 and 3). In all experiments, memory was improved for words seen as error feedback. These results are compared to the attentional boost effect (J Exp Psychol Learn Mem Cogn 39:1223-12231, 2013) and related to the orienting account for post-error slowing (Cognition 111:275-279, 2009). PMID- 26358053 TI - Sex differences in chronometric mental rotation with human bodies. AB - The present experiment investigated sex differences across stimulus types in a chronometric mental rotation task. The working hypothesis was that human bodies as stimuli would reduce the magnitude of sex differences compared to cubes as stimuli, from the embodied cognition perspective. One hundred and twenty participants, 60 men and 60 women solved chronometric mental rotation items with Shepard-Metzler cube figures, head-cubes, and human bodies, all designed so that they were similar in shape. Two figures of a given stimulus type were presented on the screen and participants had to judge if both items were mirrored or non mirrored. Results showed better mental rotation performance with human bodies than with other types of stimuli for both sexes, although the effect of stimulus type was more pronounced in men than in women. Furthermore, regardless of stimulus type, men were more accurate than women. Altogether, the results suggest that sex differences are not reduced when human bodies are used as stimuli in a chronometric task. Implications for accounts of sex differences in mental rotations are discussed. PMID- 26358054 TI - Attentional biases in ruminators and worriers. AB - This study aims to investigate whether attentional biases typically associated with depression and anxiety already exist on a sub-clinical level. A transdiagnostic characteristic, both affective disorders have in common at a sub clinical level, is persistent negative thinking (PNT), called rumination in depression and worrying in anxiety disorders. We investigated the association between these two types of PNT and attentional biases, using two different versions of the exogenous cueing tasks (ECT) in two different experiments. In Experiment 1, the cues of the ECT were negative and positive personality traits. This allowed us to investigate whether high-ruminators (N = 29), analogous to depressed patients, have difficulties to disengage attention from negative personality traits, as compared to low-ruminators (N = 40). In Experiment 2, the cues of the ECT were negative words related to themes participants frequently worry about versus positive words. This was done to investigate whether high worriers (N = 26), analogous to anxious persons, have a strong tendency to automatically direct attention toward worry-related information, as compared to low-worriers (N = 27). The results of Experiment 1 showed that high-ruminators have difficulties to disengage their attention from negative personality traits. The results of Experiment 2 indicated that there were no attentional biases for high-worriers. These results show that the attentional bias typically associated with depression is already present at a sub-clinical level, whereas this seems not to be the case for the attentional bias typically associated with anxiety. PMID- 26358055 TI - Predicting inpatient hospital payments in the United States: a retrospective analysis. AB - BACKGROUND: The Affordable Care Act (ACA) has increased rates of public and private health insurance in the United States. Increasing coverage could raise hospital revenue and reduce the need to shift costs to insured patients. The consequences of ACA on hospital revenues could be examined if payments were known for most hospitals in the United States. Actual payment data are considered confidential, however, and only charges are widely available. Payment-to-charge ratios (PCRs), which convert hospital charges to an estimated payment, have been estimated for hospitals in 10 states. Here we evaluated whether PCRs can be predicted for hospitals in states that do not provide detailed financial data. METHODS: We predicted PCRs for 5 payer categories for over 1,000 community hospitals in 10 states as a function of state, market, hospital, and patient characteristics. Data sources included the Healthcare Cost and Utilization Project (HCUP) State Inpatient Databases, HCUP Hospital Market Structure file, Medicare Provider of Service file, and state information from several sources. We performed out-of-sample prediction to determine the magnitude of prediction errors by payer category. RESULTS: Many individual, hospital, and state factors were significant predictors of PCRs. Root mean squared error of prediction ranged from 32 to over 100 % of the mean and varied considerably by which states were included or predicted. The cost-to-charge ratio (CCR) was highly correlated with PCRs for Medicare, Medicaid, and private insurance but not for self-pay or other insurance categories. CONCLUSIONS: Inpatient payments can be estimated with modest accuracy for community hospital stays funded by Medicare, Medicaid, and private insurance. They improve upon CCRs by allowing separate estimation by payer type. PCRs are currently the only approach to estimating fee-for-service payments for privately insured stays, which represent a sizable proportion of stays for individuals under age 65. Additional research is needed to improve the predictive accuracy of the models for all payers. PMID- 26358056 TI - Visceral leishmaniasis in relapsed and overtreated multiple myeloma in the era of high dose and "novel agent" therapy. PMID- 26358057 TI - Increase in myeloid-derived suppressor cells (MDSCs) associated with minimal residual disease (MRD) detection in adult acute myeloid leukemia. AB - Myeloid-derived suppressor cells (MDSCs) are thought to help provide a cellular microenvironments in many solid tumors, in which transformed cells proliferate, acquire new mutations, and evade host immunosurveillance. In the present study, we found that MDSCs (CD33 + CD11b + HLA-DR(low/neg)) in bone marrow were significantly increased in adult acute myeloid leukemia (AML) patients. MDSCs levels in newly diagnosed AML patients correlated well with extramedullary infiltration and plasma D-dimer levels. Remission rates in the MDSCs > 1500 group and MDSCs < 1500 group were 72.73 and 81.25 %, respectively. No significant differences were found between the two groups. MDSC levels in the complete remission group were significantly decreased after chemotherapy, while in the partial remission and non-remission groups, there were no significant differences. The level of MDSCs in the high minimal residual disease (MRD) group was significantly higher than that in the middle and low MRD groups. High levels of Wilms' Tumor-1 (WT-1) protein were strongly correlated with higher bone marrow MDSC levels. In conclusion, we report here a population of immunosuppressive monocytes in the bone marrow of patients with AML characterized by the CD33(high)CD11b + HLA-DR(low/neg) phenotype. These cells appear to impact the clinical course and prognosis of AML. This data may provide potentially important targets for novel therapies. PMID- 26358058 TI - Hepatic nodular lymphoid lesion with increased IgG4-positive plasma cells associated with primary biliary cirrhosis: a report of two cases. AB - The nodular lymphoid lesion of the liver known as reactive lymphoid hyperplasia or pseudolymphoma is rare and its pathogenesis is unknown. We report two cases of nodular lymphoid lesions of the liver with numerous IgG4-positive plasma cells in patients with primary biliary cirrhosis. Histologically, in both cases, the lesion showed a dense lymphoplasmacytic infiltrate with lymphoid follicles and granulomas. Fibrous tissue was scarce and without a storiform pattern. Obliterative phlebitis was not identified. The IgG4+ plasma cell counts were 82 and 76 per high power field, with an IgG4/IgG ratio of 75 and 64 %, respectively, which qualifies the lesions according to the diagnostic criteria for IgG4-related disease as " probable histological feature of IgG4-related disease ". There were no rearrangements of immunoglobulin heavy-chain genes and plasma cells had a polytypic pattern of kappa and lambda light-chain expression. The non-tumor liver showed primary biliary cirrhosis with destructive cholangitis without IgG4 plasma cells. In both cases, IgG4-related disease was not found in other organs neither at the time of diagnosis nor 3 years later. Serum IgG4 levels normalized after local ablation of the lesions. It seems unlikely that these lesions are a manifestation of IgG4-related disease. However, because the pathogenesis of both nodular lymphoid lesions and IgG4-related disease remains unclear, further studies are needed to elucidate a potential link between nodular lymphoid lesions of the liver and an increased number of IgG4 plasma cells. More definite conclusions will be possible when the pathogenesis of IgG4-related disease has been clarified. PMID- 26358061 TI - Murder of Sehzade Mustafa as an ordinary but very painful event in terms of the Ottoman history. PMID- 26358062 TI - Maternal health care use among married women in Hossaina, Ethiopia. AB - BACKGROUND: Pregnancy and child birth are natural process of continuity of life. For many it is a normal process, for some it puts life at risk impending complications. Provision of skilled care for all women before, during, and after childbirth is a key in saving women's life and ensuring delivery of healthy baby. Maternal health service drop-out through the course of pregnancy is widely claimed, yet by how much it is dropped is not known. The main aim of this study was to identify the use of maternal health service over the course of pregnancy and child birth in a comprehensive manner. METHODS: A community based cross sectional quantitative study on 623 women supported by qualitative inquiry was conducted Hossaian town, South Ethiopia during January 1-31, 2014. A structured questionnaire was used to generate the quantitative data and 4 Focus Group Discussions (FGD) were carried out to support the finding. Multiple logistic regression was used to control the effect of confounding. Odds ratios with 95% CI used to display the result of analysis. Data generated from the FGD was analyzed using thematic analysis. RESULTS: The study revealed that 87.6% of women attended at least one antenatal care (ANC). Among 546 women who attended ANC, 61.3% of the women made their first visit during second and third trimester of pregnancy and 49% had less than four antenatal visits. The study also revealed that 62.6% of deliveries were assisted by skilled attendants and 51.4% of the women received at least one postnatal check-up. Parity, pregnancy intention and awareness on danger signs of pregnancy during pregnancy were significantly associated (p < 0.05) with ANC usage. Skilled delivery attendance was significantly associated with some socio-demographic, economic and obstetric factors. Average family monthly income, awareness on obstetric danger signs of pregnancy during recent pregnancy, and frequency of ANC were positive predictors of Postnatal Care (PNC) utilization. CONCLUSIONS: Though use of maternal health care services is relatively higher, however, it is not adequate. Engaging women in their own reproductive health affairs, strengthening maternal health care, increasing community awareness about obstetric danger signs during pregnancy and child birth, and telling the benefit of family planning should be major targets for intervention. PMID- 26358063 TI - Comparison of interactive voice response (IVR) with paper administration of instruments to assess functional status, sexual function, and quality of life in elderly men. AB - PURPOSE: Patient-reported outcome (PRO) measures are essential for assessing subjective patient experiences. Interactive voice response (IVR) data collection provides advantages for clinical trial design by standardizing and centralizing the assessment. Prior to adoption of IVR as a mode of PRO administration in the Testosterone Trials (TTrials), we compared IVR to paper versions of the instruments to be used. METHODS: IVR versions of the FACIT-Fatigue scale and Psychosexual Daily Questionnaire, Question 4, were developed. In one pilot study, IVR versions of these scales were compared to paper versions in 25 men >= 65 years at each of two clinical sites. In another study, IVR versions of the SF-36 Vitality Scale (SF-36), Positive and Negative Affect Scale, and Patient Health Questionnaire were evaluated in comparison with previously validated paper versions in 25 men at two clinical sites. Both paper and IVR versions of each instrument were administered in counterbalanced order, and test-retest reliability was evaluated by repeated administration of the test. Bland-Altman plots were used to assess the degree of agreement. Test-retest correlations for each measure were also determined. RESULTS: Satisfactory agreement was observed between IVR and paper versions of each study measure. Specifically, linear and highly positive associations were observed consistently across the study for IVR and paper versions of all study measures. These ranged from r = 0.91-0.99. Test retest reliability for all measures was acceptable or better (r = 0.70-0.90). CONCLUSIONS: The IVR versions of TTrials endpoints in these two studies performed consistently well in comparison with paper versions. PMID- 26358064 TI - A new internet-based tool for reporting and analysing patient-reported outcomes and the feasibility of repeated data collection from patients with myeloproliferative neoplasms. AB - PURPOSE: An Internet-based tool for reporting and analysing patient-reported outcomes (PROs) has been developed. The tool enables merging PROs with blood test results and allows for computation of treatment responses. Data may be visualized by graphical analysis and may be exported for downstream statistical processing. The aim of this study was to investigate, whether patients with myeloproliferative neoplasms (MPNs) were willing and able to use the tool and fill out questionnaires regularly. METHODS: Participants were recruited from the outpatient clinic at the Department of Haematology, Roskilde University Hospital, Denmark. Validated questionnaires that were used were European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, Myeloproliferative Neoplasm Symptom Assessment Form, Brief Fatigue Inventory and Short Form 36 Health Survey. Questionnaires were filled out >= 6 months online or on paper according to participant preference. Regularity of questionnaire submission was investigated, and participant acceptance was evaluated by focus group interviews. RESULTS: Of 135 invited patients, 118 (87 %) accepted participation. One hundred and seven participants (91 %) preferred to use the Internet-based tool. Of the 118 enrolled participants, 104 (88 %) submitted PROs regularly >= 6 months. The focus-group interviews revealed that the Internet based tool was well accepted. CONCLUSION: The Internet-based approach and regular collection of PROs are well accepted with a high participation rate, persistency and adherence in a population of MPN patients. The plasticity of the platform allows for adaptation to patients with other medical conditions. PMID- 26358065 TI - High cell density cultivation of the chemolithoautotrophic bacterium Nitrosomonas europaea. AB - Nitrosomonas europaea is a chemolithoautotrophic nitrifier, a gram-negative bacterium that can obtain all energy required for growth from the oxidation of ammonia to nitrite, and this may be beneficial for various biotechnological and environmental applications. However, compared to other bacteria, growth of ammonia oxidizing bacteria is very slow. A prerequisite to produce high cell density N. europaea cultures is to minimize the concentrations of inhibitory metabolic by-products. During growth on ammonia nitrite accumulates, as a consequence, N. europaea cannot grow to high cell concentrations under conventional batch conditions. Here, we show that single-vessel dialysis membrane bioreactors can be used to obtain substantially increased N. europaea biomasses and substantially reduced nitrite levels in media initially containing high amounts of the substrate. Dialysis membrane bioreactor fermentations were run in batch as well as in continuous mode. Growth was monitored with cell concentration determinations, by assessing dry cell mass and by monitoring ammonium consumption as well as nitrite formation. In addition, metabolic activity was probed with in vivo acridine orange staining. Under continuous substrate feed, the maximal cell concentration (2.79 * 10(12)/L) and maximal dry cell mass (0.895 g/L) achieved more than doubled the highest values reported for N. europaea cultivations to date. PMID- 26358060 TI - Mesenchymal tumours of the mediastinum--part II. AB - This is the second part of a two-part review on soft tissue tumours which may be encountered in the mediastinum. This review is based on the 2013 WHO classification of soft tissue tumours and the 2015 WHO classification of tumours of the lung, pleura, thymus and heart and provides an updated overview of mesenchymal tumours that have been reported in the mediastinum. PMID- 26358059 TI - Mesenchymal tumours of the mediastinum--part I. AB - The mediastinum is an anatomically defined space in which organs and major blood vessels reside with surrounding soft tissue elements. The thymus is an important organ in the mediastinum, and many of the masses encountered in the mediastinum are related to this organ. Most neoplasms diagnosed in the mediastinum are epithelial tumours (thymomas and thymic carcinomas), lymphomas or germ cell tumours. In contrast, soft tissue tumours of the mediastinum are rare. In 1963, Pachter and Lattes systematically reviewed soft tissue pathology of the mediastinum, covering the hitherto described [2, 226, 227] In this review, based on the 2013 WHO classification of soft tissue tumours and the 2015 WHO classification of tumours of the lung, pleura, thymus and heart, we provide an updated overview of mesenchymal tumours that may be encountered in the mediastinum. PMID- 26358066 TI - Yeasts associated with an abandoned mining area in Pernek and their tolerance to different chemical elements. AB - Four plants, Cirsium arvense (creeping thistle), Equisetum arvense (field horsetail), Oxalis acetosella (wood sorrel) and Phragmites australis (common reed), which grew in an abandoned Sb-mining area in Pernek (Male Karpaty Mts., Slovakia), were investigated for the yeast species. Yeasts were isolated from both the leaves of the plants and the soil adjacent to the plants. In total, 65 yeast cultures, belonging to 11 ascomycetous and 5 basidiomycetous yeast species, were isolated. The species most frequently isolated from both the soil and leaf samples were Trichosporon porosum, Galactomyces candidus and Candida solani, whereas Aureobasidium pullulans, Candida tsuchiyae and Sporidiobolus metaroseus were isolated exclusively from the plant leaves. All the yeast species isolated were tested for their tolerance to two heavy metals (Cd, Zn) and three metalloids (As, Sb and Si). The yeasts isolated from both the leaves and soils exhibited a high tolerance level to both As and Sb, present in elevated concentrations at the locality. Among the yeast species tested, Cryptococcus musci, a close relative to Cryptococcus humicola, was the species most tolerant to all the chemical elements tested, with the exception of Si. It grew in the presence of 200 mmol/L Zn, 200 mmol/L Cd, 60 mmol/L As and 50 mmol/L Sb, and therefore, it can be considered as a multi-tolerant species. Some of the yeast species were tolerant to the individual chemical elements. The yeast-like species Trichosporon laibachii exhibited the highest tolerance to Si of all yeasts tested, and Cryptococcus flavescens and Lindnera saturnus showed the same tolerance as Cryptococcus musci to Zn and As, respectively. The majority of the yeasts showed a notably low tolerance to Cd (not exceeded 0.5 mmol/L), which was present in small amounts in the soil. However, Candida solani, isolated from the soil, exhibited a higher tolerance to Cd (20 mmol/L) than to As (2 mmol/L). PMID- 26358068 TI - Young age of onset colorectal cancers. AB - BACKGROUND: Colorectal cancer is typically a condition of older patients with only 10 % diagnosed under the age of 50 years. Often, diagnosis is delayed, but certain factors such as inherited syndromes, inflammatory bowel disease, or a family history of colorectal cancer should heighten the clinician's awareness. This study of young colorectal cancers describes the incidence of potential contributory factors that warrant early investigations and their effect on survival outcomes. METHODS: A single-institution colorectal cancer database was queried for patients diagnosed with colorectal cancer under the age of 50. Medical records were reviewed, and patients were grouped into familial, inflammatory bowel disease-related, or sporadic cancers. Sporadic cancers without existing family history were further evaluated for genetic and molecular changes including mutations in the oncogenes KRAS and BRAF, microsatellite instability, and methylator phenotype. RESULTS: One hundred thirty-five patients under the age of 50 with colorectal cancer diagnosed between 1994 and 2004 were identified. Slightly under half, (44.4 %) were women. Mean age at surgery was 42.1 +/- 6.7 years. Nineteen patients (14 %) had a hereditary colorectal cancer syndrome (11 hereditary non-polyposis colorectal cancer (HNPCC), 8 familial adenomatous polyposis (FAP)), and 19 (14 %) had inflammatory bowel disease (14 ulcerative colitis, 5 Crohn's). Three patients had other cancers (brain, breast, and endometrial) and 20 % of patients had a family history of colorectal cancer outside of a defined syndrome. Overall, age-standardized 5-year survival was 66.8 % (stage I 100 %, stage II 76.5 %, stage III 63.0 %, and stage IV 0 %). Patients with genetic predisposition and inflammatory bowel disease had better 5-year survival when compared to the sporadic group (p = 0.025). Molecular profiles were available for 71 of the 77 sporadic cancers. All 71 tumors were microsatellite stable, and none had CpG island methylator phenotype. Twenty-three (32.4 %) were KRAS mutant. CONCLUSION: In our cohort, a family history of colorectal cancer, known hereditary colorectal cancer syndrome, and inflammatory bowel disease account for nearly half of all cases of young colorectal cancer. Prompt investigation of symptoms is essential in patients with Sporadic early-onset colorectal cancers, which appear to arise through the classical adenoma-to carcinoma sequence. PMID- 26358067 TI - Fermented infant formulas without live bacteria: a systematic review. AB - Fermented formulas, i.e., those fermented with lactic acid-producing bacteria during the production process and not containing significant amounts of viable bacteria in the final product, are widely available in many countries. Our aim was to systematically review published evidence related to the safety and health effects of the administration of fermented infant formulas compared with standard infant formulas. The Cochrane Library, MEDLINE, and EMBASE databases and major pediatric conference proceedings were searched. Five randomized controlled trials (RCTs) involving 1326 infants met the inclusion criteria. Compared with standard formula, the use of fermented formula resulted in a similar weight gain and length gain during the study period. Data from one RCT, albeit large, suggest the effectiveness of fermented formula in preventing and treating acute diarrhea. Fermented formula has the potential to reduce some, albeit not well-defined, digestive symptoms. Current evidence does not support the use of fermented formula for preventing cow's milk allergy. CONCLUSION: Limited available evidence suggests that the use of fermented infant formula, compared with the use of standard infant formula, does not offer clear additional benefits, although some benefit on gastrointestinal symptoms cannot be excluded. What is known * Fermented formulas, i.e., those fermented with lactic acid-producing bacteria during the production process and not containing significant amounts of viable bacteria in the final product, are widely available in many countries. What is new * Limited evidence available suggests that the use of fermented infant formula, compared with the use of standard infant formula, does not offer clear additional benefits, although some benefit on gastrointestinal symptoms cannot be excluded. At the same time, no negative health effects have been documented. PMID- 26358069 TI - Synopsis of the species of the genus Sphaeromyxa Thelohan, 1892 (Myxosporea: Bivalvulida: Variisporina: Sphaeromyxidae). AB - Sphaeromyxa spp. are parasites of marine fishes, infecting the gall-bladders or bile ducts. The spores of these species possess characteristic ribbon-like polar filaments, a unique character among myxozoans. This unique character is also a synapomorphy consistent with estimates of phylogeny for this group which forms a lineage distinct from other myxozoans. There are 49 nominal species of Sphaeromyxa Thelohan, 1892 for which a synopsis is provided, reporting spore dimensions, spore shape, locality, and host species. A line drawing is also provided for each species. PMID- 26358070 TI - Three new species of Myxobolus Butschli, 1882 (Myxozoa: Myxobolidae) infecting the common nase Chondrostoma nasus (L.) in the River Danube. AB - The common nase Chondrostoma nasus (L.) is a frequent cyprinid fish in the River Danube. In a survey on its infection with myxosporeans, eight different Myxobolus spp. spore types were found in the gills, swim bladder, fins and intestinal wall. Of these, spore types representing three species were studied in detail by morphological and molecular methods. Based on the differences in 18S rDNA sequences, two new species of Myxobolus Butschli, 1882 from the gills and one from the swim bladder are described: M. arrabonensis n. sp., M. szentendrensis n. sp. and M. paksensis n. sp. The new species resembled M. muelleri Butschli, 1882, M. intimus Zaika, 1965 and M. cycloides Gurley, 1893, all parasitic in leuciscine cyprinids, in spore size and location in the host, but exhibited differences in partial 18S rDNA sequences as follows: M. arrabonensis - M. muelleri (1.4%), M. szentendrensis - M. intimus (2.8%), M. paksensis - M. cycloides (2.4%). Based on the significant differences in rDNA sequences, the three forms are considered to represent new, hitherto undescribed species in spite of their morphological similarities to some Myxobolus spp. forming spores in identical locations in genetically closely related cyprinids of the subfamily Leuciscinae. PMID- 26358071 TI - Nematodes of Heligmonellidae (Strongylida) of Pogonomys championi Flannery and Pogonomys sylvestris Thomas (Rodentia: Muridae) from Papua New Guinea with descriptions of five new species. AB - Eight species of heligmonellid nematodes including five new species and a putative new species were identified from the digestive tracts of 12 Pogonomys championi Flannery and 27 P. sylvestris Thomas (Murinae: Hydromyini) from Papua Indonesia. Hasanuddinia pogonomyos Smales, 2014 had been previously described from P. loriae Thomas and P. macrourus (Milne-Edwards) and Odilia mackerrasae (Mawson, 1961) from several endemic rodent species. Bunomystrongylus ilami n. sp. can be distinguished from its congeners by the number of rounded ridges in the synlophe; Hasanuddinia hasegawai n. sp. by the number of ridges, three ventral being hypertrophied, in the synlophe; Montistrongylus kaindiensis n. sp. by the number of ridges in the synlophe and the length of the spicules; Odilia helgeni n. sp. in the characters of the synlophe ridges; Odilia whittingtoni n. sp. in the characters of the synlophe ridges and the length of the spicules. Species richness of the nematode assemblage of P. sylvestris, nine species and a juvenile heligmonellid, was comparable to those of P. loriae and P. macrourus but that of P. championi, five species, was considered depauperate. Species composition showed both commonalities between the host species as well as distinctive features. Three of five species in the assemblage were unique to P. championi and five of nine species to P. sylvestris. PMID- 26358072 TI - Meteterakis saotomensis n. sp. (Nematoda: Heterakidae) from Schistometopum thomense (Bocage) (Gymnophiona: Dermophiidae) on Sao Tome Island. AB - Meteterakis saotomensis n. sp. is described from Schistometopum thomense (Bocage), a gymnophionan endemic to the oceanic island of Sao Tome in the Gulf of Guinea. The specimens were assigned to Meteterakis Karve, 1930, based on the possession of a head with three rounded lips, not set-off from the body, the absence of interlabia and cordons, females with a long vagina and males with a preanal sucker, surrounded by a cuticularised rim and caudal alae that are supported by fleshy papillae. The new species is characterised by: body length 4.2-4.5 mm (males) and 5.1-6.4 mm (females); total length of oesophagus, including pharyngeal portion and oesophageal bulb, 820-856 um (males) and 898 1,070 um (females); length of pharynx 57-58 um (males) and 65-68 um (females); spicules equal, 410-521 um long, with tessellated ornamentation throughout their length and alae, and with bevelled tip; gubernaculum or 'gubernacular mass' absent; tail length 164-176 um (males) and 214-239 um (females), with elongated tip; vulva at 2.3-2.8 mm from anterior end, with anterior lip forming small flap. This is the second species of Meteterakis reported from gymnophionan hosts and the first from the Afrotropical region. Selected comparative morphological data for Meteterakis spp. are presented, and data on host range and geographic distribution are updated. The name M. striaturus Oshmarin & Demshin, 1972 is corrected to M. striatura to reflect the female gender of the genus name. PMID- 26358073 TI - Porrocaecum parvum n. sp. and P. reticulatum (Linstow, 1899) (Nematoda: Ascaridoidea) from birds in China. AB - Porrocaecum parvum n. sp. is described from the grey-faced buzzard Butastur indicus (Gmelin) (Accipitriformes: Accipitridae) in China. The new species differs from its congeners in having well-developed cervical alae, small interlabia and very short intestinal caecum (0.34 mm long, representing 11.9% of oesophageal length) and in the number and arrangement of the caudal papillae (29 pairs in total, arranged as follows: 21 pairs precloacal, single double pair paracloacal and seven pairs postcloacal) and in the morphology of the male tail. In addition, Porrocaecum reticulatum (Linstow, 1899), collected from the purple heron Ardea purpurea L., the grey heron A. cinerea L. and the little egret Egretta garzetta (L.) (Pelecaniformes: Ardeidae) in China, was also studied using light and, for the first time, scanning electron microscopy. Previously unreported and erroneous morphological features of taxonomic significance are revealed, including the presence of narrow cervical alae, single pair of small, submedial pores and single, short medial ditch on each lip, interlabia with very pointed anterior prolongation, single medio-ventral precloacal papilla on anterior cloacal lip and double paracloacal papillae slightly posterior to cloaca. PMID- 26358074 TI - A new species of Anchistrotos Brian, 1906 (Copepoda: Cyclopoida: Taeniacanthidae) from the filamentous shrimpgoby Myersina filifer (Valenciennes) (Perciformes: Gobiidae) in Korean waters. AB - A new species of Anchistrotos Brian, 1906 (Copepoda: Cyclopoida: Taeniacanthidae), parasitic in the branchial cavities of the filamentous shrimpgoby Myersina filifer (Valenciennes) (Perciformes: Gobiidae) from Korea is described. The new species is most closely related to A. tangi Venmathi Maran, Moon & Adday, 2014, but differs from it by the following combination of characters in the adult female: the U-shaped rostrum, the distal margin of the anal somite lacks patches of spinules, the proximal segment of the maxilliped is without seta, and the maxilliped claw is armed with long and small naked setae. This is the tenth species of the genus and a key is provided to distinguish all nominal species. PMID- 26358075 TI - Dollfusiella qeshmiensis n. sp. (Cestoda: Trypanorhyncha) from the cowtail stingray Pastinachus sephen (Forsskal) in the Persian Gulf, with a key to the species of Dollfusiella Campbell & Beveridge, 1994. AB - A new species of the genus Dollfusiella Campbell & Beveridge, 1994 is described from Pastinachus sephen (Forsskal) in the Persian Gulf. Dollfusiella qeshmiensis n. sp. is allocated to the genus Dollfusiella based on the possession of two bothria, prebulbar organs, a heteroacanthous typical armature with tightly spaced rows of hollow hooks, a basal swelling and a characteristic basal armature without prominent macrohooks. The presence of an enlarged external seminal vesicle in Dollfusiella qeshmiensis n. sp. distinguishes this species from D. michiae (Southwell, 1929), D. bareldsi (Beveridge, 1990), D. owensi (Beveridge, 1990), D. geraschmidti (Dollfus, 1974), D. angustiformis Schaeffner & Beveridge, 2013, D. hemispinosa Schaeffner & Beveridge, 2013, D. spinosa Schaeffner & Beveridge, 2013 and D. taminii Menoret & Ivanov, 2014. The new species is distinguished from the remaining species within the genus by a combination of the following morphological features: the number of testes per segment, the number of testis columns and the number of homeomorphous hooks per half spiral row in the metabasal region. In the most recent taxonomic key to the species of Dollfusiella, the presence or absence of enlarged, microscopically visible spinitriches on the scolex was used as the first distinguishing character dividing the congeners into two groups. Since the existence of visible microtriches on the scolex peduncle of D. vooremi (Sao Clemente & Gomes, 1989), a species so far grouped among the species lacking visible microtriches on the scolex, has been recently demonstrated, and given the fact that the presence of microscopically visible microtriches on the scolex is variable in some eutetrarhynchid species, a new key to the species of Dollfusiella is provided in which the spinitriches have been given less priority. PMID- 26358076 TI - Characterisation of Isospora lusitanensis n. sp. (Apicomplexa: Eimeriidae) from the Eurasian blackbird Turdus merula Linnaeus (Passeriformes: Turdidae) in mainland Portugal. AB - A new coccidian species (Protozoa: Apicomplexa: Eimeriidae) is described from a specimen of the Eurasian blackbird Turdus merula Linnaeus held for rehabilitation and reintroduction into the wild in a centre for research and recovery of wild animals in Quinta de Marim, Olhao, Portugal. Isospora lusitanensis n. sp. has subspherical to ovoidal oocysts, measuring on average 26.4 * 23.4 MUm, with smooth, bi-layered wall c.1.1 MUm thick. Micropyle and oocyst residuum are absent, but a polar granule is present. Sporocysts are ellipsoidal, measuring on average 16.0 * 10.9 um. Stieda body is knob-like and sub-Stieda body is prominent and rounded. Sporocyst residuum is composed of scattered spherules. Sporozoites are vermiform, with one refractile body and a nucleus. The morphological and morphometric data for the new species were compared with those for species parasitising birds of the Muscicapidae, Turdidae, Timaliidae, Troglodytidae and Cinclidae, which are considered phylogenetically close. The original histograms of Isospora turdi Schwalbach, 1959 were redrawn for comparison with I. lusitanensis n. sp. and a linear regression of width against length of the oocysts is presented for characterisation. This is the first isosporoid coccidian described from T. merula in mainland Portugal. PMID- 26358077 TI - ZLL/AGO10 maintains shoot meristem stem cells during Arabidopsis embryogenesis by down-regulating ARF2-mediated auxin response. AB - BACKGROUND: The shoot meristem gives rise to new organs throughout a plant's life by the activity of pluripotent stem cells in the meristem center. Organ initiation at the periphery of the shoot meristem is triggered by the accumulation of the phytohormone auxin at the initiation site. Loss-of-function mutants of the ZWILLE/ARGONAUTE10/PINHEAD (ZLL/AGO10/PNH) gene terminate shoot meristem stem cells late in embryogenesis and can form a leaf or a leaf-like structure instead, indicating that AGO10 activity is required to maintain shoot meristem stem cells undifferentiated. RESULTS: Here, we addressed whether stem cell maintenance by AGO10 involves regulation of auxin. We found that in zll-1 mutants, auxin accumulation and expression of the response reporter DR5:GFP are elevated, and transcription of the Auxin Response Factor 2 (ARF2) gene is upregulated. Downregulation of ARF2 significantly restores stem cells in zll-1 mutants, whereas increased expression of ARF2 enhances differentiation of stem cells in zll-1 mutants. We further found that upregulation of the AGO10 effector gene REVOLUTA restores ARF2 expression and stem cell maintenance in zll-1 embryos. CONCLUSIONS: Our results indicate that maintenance of shoot meristem stem cells by AGO10 involves negative regulation of auxin signaling and, via REV mediated downregulation of ARF2 expression, auxin response. PMID- 26358079 TI - [Workplace health promotion among elderly employees in Germany. Results in the IAB establishment panel 2011]. AB - AIM: The aim of the secondary analysis is the exploration of the prevalence and determinants of workplace health promotion among elderly employees. MATERIAL AND METHODS: The Institute for Employment Research (IAB) establishment panel is an annual representative survey of employers. In 2011 a total of 13,378 establishments with at least 1 elderly employee (50 + years) participated in personal interviews. RESULTS: In 2011, 4 % of the establishments in Eastern and Western Germany included measures for workplace health promotion among employees aged 50 years and older, which were often associated with personnel measures among the elderly. The prevalence of workplace health promotion varies considerably among the sectors of industry and the Federal States and substantially increases with the size of the establishment. Establishments with a works council are disproportionally highly committed to workplace health promotion among the elderly employees. CONCLUSION: There is a large development potential for a better integration of workplace health promotion among elderly employees in personnel and enterprise strategies. PMID- 26358078 TI - Aldehyde Dehydragenase 1 and Nodal as Significant Prognostic Markers in Colorectal Cancer. AB - This study aimed to analyze prognostic significance of aldehyde dehydragenase 1 (ALDH1) and Nodal expression in patients with colorectal cancer. ALDH1 and Nodal expressions were observed based on the immunohistochemistry staining from 108 colorectal cancer patients. Scores were given to the staining intensity and percentage of positive cells, and sum of two scores for each case was used to define the groups of ALDH1 and Nodal. We also investigated the protein and mRNA levels of ALDH1 and Nodal by Western blot and qRT-PCR assays. The results were analyzed with the clinicopathologic parameters of these patients. The results indicated that expressions of ALDH1 and Nodal were significantly correlated with the differentiation degree, metastasis, number of tumor positive lymph nodes and AJCC stage. ALDH1 was inclined to express more in the worse differentiated degrees, lymph node metastasis, and worse AJCC stage of colorectal cancer patients. And the expression of Nodal was inversely compared with ALDH1.While the expression of ALDH1 was inversely correlated with the Nodal (r = -0.709, P < 0.01). PMID- 26358080 TI - Effect of teriparatide on repair of femoral metaphyseal defect in ovariectomized rats. AB - OBJECTIVE: This study aimed to investigate the effect exerted by teriparatide on the repair of femoral metaphyseal defect in ovariectomized rats. METHOD: Female Sprague-Dawley rats were ovariectomized and after 3 months a critically sized defect of 3 mm in diameter-a through-hole bone defect-was drilled into each distal femur of the ovariectomized rats. The rats were injected with teriparatide (30 MUg/kg) parathyroid hormone (PTH) in the peritoneum three times per week. After 4 and 8 weeks the animals were killed and the blood and bilateral femora were harvested for biochemical analysis, histopathological observation, and micro computed tomography (CT) examination. RESULTS: The PTH group and control group were compared 4 and 8 weeks after surgery. PTH increased bone formation in the defect area. Moreover, PTH showed the strongest effects on bone volume per total volume, trabecular number, trabecular thickness, trabecular separation, and total fluorescence-marked new bone area. Additionally, the PTH treatment group showed inhibited serum concentrations of C-terminal telopeptide of type I collagen and enhanced expression of calcium, phosphorus, and bone alkaline phosphatase. CONCLUSION: Our findings suggest a positive effect of PTH on defect healing in ovariectomized rats. PMID- 26358081 TI - Norepinephrine induced epithelial-mesenchymal transition in HT-29 and A549 cells in vitro. AB - PURPOSE: Norepinephrine (NE) has been implicated in epithelial-mesenchymal transition (EMT) of cancer cells. However, the underlying mechanism is poorly understood. The goal of this study was to explore the effect of NE on cancer cell EMT and to investigate the potential mechanism. METHODS: HT-29 and A549 cells were treated with NE, beta-adrenergic receptor (beta-AR) antagonist (propranolol) or inhibitor of transforming growth factor-beta (TGF-beta) receptor type I kinase (Ly2157299). Morphology of cells was observed with optical and electron microscope and immunofluorescence staining. Cellular migration and invasion were tested with transwell migration assay and Matrigel invasion assay, respectively. TGF-beta1 and cyclic adenosine monophosphate (cAMP) were quantified. EMT markers and signaling pathway were measured by RT-PCR and western blot. RESULTS: NE stimulated TGF-beta1 secretion and intracellular cAMP synthesis, induced morphological alterations in HT-29 and A549 cells, and enhanced their ability of migration and invasion. EMT markers induction was observed in NE-treated cancer cells. The effect of NE could be inhibited by propranolol or Ly2157299. beta AR/TGF-beta1 signaling/p-Smad3/Snail and beta-AR/TGF-beta1 signaling/HIF 1alpha/Snail were two signaling pathways. CONCLUSION: These findings demonstrated that TGF-beta1 signaling pathway was a significant factor of NE-induced cancer cells EMT. The data also suggested that psychological stress might be a risk factor which enhances the ability of migration or invasion of cancer cells. PMID- 26358082 TI - Induction of ROS generation and NF-kappaB activation in MARC-145 cells by a novel porcine reproductive and respiratory syndrome virus in Southwest of China isolate. AB - BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) is the cause of an economically important swine disease that has devastated the swine industry since the late 1980s. The aim of the present study was to investigate the interaction between reactive oxygen species (ROS) and NF-kappaB by PRRSV infection. RESULTS: We isolated the local strain of PRRSV from southwest China, designated YN-2011, then sequenced and analyzed the genome. YN-2011 was then used to evaluate the interaction of ROS and NF-kappaB. In PRRSV infected MARC-145 cells, there was a time-dependent increase in ROS and Maleic Dialdehyde (MDA). Accordingly, NF-kappaB activation was also increased as PRRSV infection progressed. Degradation of IkappaB mRNA was detected late in PRRSV infection, and overexpression of the dominant negative form of IkappaBalpha significantly suppressed NF-kappaB induced by PRRSV. CONCLUSIONS: The results indicate that the generation of ROS is involved in PRRSV replication and this progression is associated with the alteration in NF-kappaB activity induced by ROS. These results should extend our better understanding the interaction between PRRSV and host MARC-145 cells. PMID- 26358083 TI - Rubidium-82 uptake in metastases from neuroendocrine tumors: No flow response to adenosine. PMID- 26358084 TI - Assessment of left ventricular mechanical dyssynchrony in coronary artery disease. PMID- 26358085 TI - Differential risk reclassification improvement by exercise testing and myocardial perfusion imaging in patients with suspected and known coronary artery disease. AB - OBJECTIVE: The objective of this study is to compare the incremental prognostic and net risk reclassification value of exercise testing alone vs exercise myocardial perfusion imaging (MPI) for estimating the risk of death in patients with suspected and known coronary artery disease (CAD). METHODS: 6702 patients with suspected CAD and 2008 with known CAD had treadmill exercise MPI and were followed for 2.5 +/- 0.9 years for the occurrence of all-cause death. The estimation of risk of death and net reclassification improvement (NRI) were examined in three models. Model 1: clinical variables; Model 2: model 1+Duke Treadmill Score; and Model 3: model 2+ MPI variables. Risk estimates were categorized as <1%, 1-3%, and >3% risk of death per year. RESULTS: In patients with suspected CAD, the global Chi-square for predicting risk of death increased significantly for Model 2 compared to Model 1 (74.78 vs 63.86 to (P = .001). However, adding MPI variables in Model 3 did not further improve predictive value (Chi-square 79.38, P = .10). In patients with suspected CAD risk, reclassification improved significantly in Model 2 over Model 1 (NRI = 0.12, 95% CI 0.02 to 0.22, P = .019), but not in Model 3 (NRI = 0.0009, 95% CI -0.072 to 0.070; P = .98). In contrast, in patients with known CAD Model 2 did not yield significant improvements for predicting risk and risk reclassification compared to Model 1. However, global Chi-square of Model 3 was significantly higher than that of Model 2 (30.03 vs 6.56, P < .0001) with associated significant reclassification improvement (NRI = 0.26 95% CI 0.067 to 0.46. P = .0084). CONCLUSION: Risk reclassification by diagnostic testing is importantly influenced by baseline characteristics of patient cohorts. In patients with suspected CAD, NRI is predominately achieved by exercise variables, whereas in patients with known CAD, greatest NRI is obtained by MPI variables. PMID- 26358087 TI - Combination therapy with bortezomib, continuous low-dose cyclophosphamide and dexamethasone followed by one year of maintenance treatment for relapsed multiple myeloma patients. AB - Combination therapy for longer periods but at low dose might be an effective and tolerable manner to treat patients with relapsed multiple myeloma (MM). We used bortezomib, dexamethasone and low-dose oral cyclophosphamide as an induction regimen, followed by 1 year of maintenance consisting of bortezomib and cyclophosphamide. Relapsed MM patients were treated with six cycles of bortezomib twice weekly, cyclophosphamide 50 mg daily and dexamethasone. Maintenance therapy was given for 1 year. Primary endpoints were toxicity during re-induction and maintenance therapy. Secondary endpoints were response to treatment and progression-free (PFS) and overall survival (OS). This study included 59 patients. Myelosuppression and neuropathy were the most common side effects. Median follow-up was 27.1 (0.46-54.4) months with an overall response of 71%, and a very good partial response or more of 33%. During maintenance, improved responsiveness was observed in 19% of the patients. The median PFS was 18.4 months (range 0.13-43.5) and the median OS was 28.1 months (range 0.13-54.4). In conclusion, our study demonstrates that treatment with bortezomib, dexamethasone and low-dose cyclophosphamide is an effective and manageable regimen. Adding 1 year of maintenance was feasible, with limited side effects and an increased response rate. PMID- 26358086 TI - Experimental study of the protective effects of SYVN1 against diabetic retinopathy. AB - Genetic factors play an important role in the pathogenesis of diabetic retinopathy (DR). While many studies have focused on genes that increase susceptibility to DR, herein, we aimed to explore genes that confer DR resistance. Previously, we identified Hmg CoA reductase degradation protein 1 (SYVN1) as a putative DR protective gene via gene expression analysis. Transgenic mice overexpressing SYVN1 and wild-type (WT) mice with streptozotocin-induced diabetes were used in this experiment. Retinal damage and vascular leakage were investigated 6 months after induction of diabetes by histopathological and retinal cell apoptosis analyses and by retinal perfusion of fluorescein isothiocyanate-conjugated dextran. Compared with diabetic WT mice, diabetic SYVN1 mice had significantly more cells and reduced apoptosis in the retinal ganglion layer. Retinal vascular leakage was significantly lower in diabetic SYVN1 mice than in diabetic WT mice. The expression levels of endoplasmic reticulum (ER) stress-related, pro-inflammatory, and pro-angiogenic genes were also analyzed. Lower expression levels were observed in diabetic SYVN1 mice than in WT controls, suggesting that SYVN1 may play an important role in inhibiting ER stress, chronic inflammation, and vascular overgrowth associated with DR. Thus, these results strongly supported our hypothesis that SYVN1 confers DR resistance. PMID- 26358088 TI - Testing the dimensional structure of DSM-5 posttraumatic stress disorder symptoms in a nonclinical trauma-exposed adolescent sample. AB - BACKGROUND: The current study investigated the underlying dimensionality of DSM-5 posttraumatic stress disorder (PTSD) symptoms in a trauma-exposed Chinese adolescent sample using a confirmatory factor analytic (CFA) alternative model approach. METHODS: The sample consisted of 559 students (242 females and 314 males) ranging in age from 12 to 18 years (M = 15.8, SD = 1.3). Participants completed the PTSD Checklist for DSM-5, the Major Depression Disorder and Panic Disorder subscales of the Revised Children's Anxiety and Depression Scale, and the Aggressive Behavior subscale of the Youth Self-Report. RESULTS: Confirmatory factor analytic results indicated that a seven-factor model comprised of intrusion, avoidance, negative affect, anhedonia, externalizing behavior, anxious arousal, and dysphoric arousal factors emerged as the best-fitting model. Further analyses showed that the external measures of psychopathological variables including major depressive disorder, panic disorder, and aggressive behavior were differentially associated with the resultant factors. CONCLUSIONS: These findings support and extend previous findings for the newly refined seven-factor hybrid model, and carry clinical and research implications for trauma-related psychopathology. PMID- 26358089 TI - Education for Professional Chaplains: Should Certification Competencies Shape Curriculum? AB - The growing importance of professional chaplains in patient-centered care has raised questions about education for professional chaplaincy. One recommendation is that the curricula of Clinical Pastoral Education (CPE) residency programs make use of the chaplaincy certification competencies. To determine the adoption of this recommendation, we surveyed CPE supervisors from 26 recently re accredited, stipended CPE residency programs. We found the curricula of 38% of these programs had substantive engagement with the certification competencies, 38% only introduced students to the competences, and 23% of the programs made no mention of them. The majority of the supervisors (59%) felt engagement with the competencies should be required while 15% were opposed to such a requirement. Greater engagement with chaplaincy certification competencies is one of several approaches to improvements in chaplaincy education that should be considered to ensure that chaplains have the training needed to function effectively in a complex and changing healthcare environment. PMID- 26358092 TI - The impact of digital DNA counting technologies on noninvasive prenatal testing. AB - The discovery of cell-free DNA molecules in maternal plasma has opened up numerous opportunities for noninvasive prenatal testing. The advent of new digital counting technologies, including digital polymerase chain reaction and massive parallel sequencing, has provided the opportunity to quantify the cell free DNA molecules in maternal plasma in an unprecedentedly precise manner. Powered by these technologies, prenatal testing of different kinds of hereditary conditions, ranging from monogenic diseases to chromosome aneuploidies, has been shown to be possible through the analysis of maternal plasma DNA. Discussed here are the principles of the approaches used in the noninvasive testing of different fetal conditions, with an emphasis on the impact that different digital DNA counting strategies have made on the development of these tests. PMID- 26358093 TI - Hydrated Ions: From Individual Ions to Ion Pairs to Ion Clusters. AB - The structure of hydrated ions plays a central role in chemical and biological sciences. In the present paper, five ions, namely, Na(+), K(+), Mg(2+), Ca(2+) and Cl(-), are examined using molecular dynamics simulations. In addition to hydrated individual ions and ion pairs identified previously, hydrated ion clusters containing 3, 4, 5, or more ions are identified in the present paper. The dependence of hydration numbers and mole fractions of individual ions, ion pairs, and larger ion clusters on the electrolyte concentration is determined. As the electrolyte concentration increases, the mole fraction of hydrated individual ions decreases, and the mole fraction of hydrated larger ion clusters increases. The results also reveal that the hydrogen bonding numbers of the H2O molecules of the first hydration shells of individual ions, ion pairs, and larger ion clusters are insensitive to the electrolyte concentration, but sensitive to the nature and conformation of ions. PMID- 26358094 TI - Middle Latency Auditory Evoked Potential (MLAEP) in Workers with and without Tinnitus who are Exposed to Occupational Noise. AB - BACKGROUND: Tinnitus is an important occupational health concern, but few studies have focused on the central auditory pathways of workers with a history of occupational noise exposure. Thus, we analyzed the central auditory pathways of workers with a history of occupational noise exposure who had normal hearing threshold, and compared middle latency auditory evoked potential in those with and without noise-induced tinnitus. MATERIAL AND METHODS: Sixty individuals (30 with and 30 without tinnitus) underwent the following procedures: anamnesis, immittance measures, pure-tone air conduction thresholds at all frequencies between 0.25-8 kHz, and middle latency auditory evoked potentials. RESULTS: Quantitative analysis of latencies and amplitudes of middle latency auditory evoked potential showed no significant differences between the groups with and without tinnitus. In the qualitative analysis, we found that both groups showed increased middle latency auditory evoked potential latencies. The study group had more alterations of the "both" type regarding the Na-Pa amplitude, while the control group had more "electrode effect" alterations, but these alterations were not significantly different when compared to controls. CONCLUSIONS: Individuals with normal hearing with or without tinnitus who are exposed to occupational noise have altered middle latency auditory evoked potential, suggesting impairment of the auditory pathways in cortical and subcortical regions. Although differences did not reach significance, individuals with tinnitus seemed to have more abnormalities in components of the middle latency auditory evoked potential when compared to individuals without tinnitus, suggesting alterations in the generation and transmission of neuroelectrical impulses along the auditory pathway. PMID- 26358095 TI - Vitamin D receptor FokI, BsmI, and TaqI polymorphisms and susceptibility to rheumatoid arthritis : A meta-analysis. AB - OBJECTIVE: The aim of this study was to explore whether vitamin D receptor (VDR) polymorphisms are associated with susceptibility to rheumatoid arthritis (RA). METHODS: Meta-analyses were conducted on the associations between the VDR FokI, BsmI, and TaqI polymorphisms and RA. RESULTS: A total of seven studies were considered in the meta-analysis, involving a total of 923 patients and 912 controls. Meta-analysis of the VDR FokI polymorphism showed no association between RA and the F allele in the entire studied cohort (odds ratio, OR = 1.1740, 95 % confidence interval, CI = 0.994-1.387, p = 0.059). However, stratification by ethnicity revealed a significant association between the F allele and RA in Europeans (OR = 1.402, 95 % CI = 1.126-1.746, p = 0.003). Furthermore, an association was found between RA and the VDR FokI polymorphism using both the dominant model and homozygote contrast. Meta-analysis revealed no association between RA and the VDR BsmI B and TaqI T polymorphisms in Europeans (OR for the B allele = 1.065, 95 % CI = 0.911-1.245, p = 0.427; OR for the T allele = 1.065, 95 % CI = 0.834-1.361, p = 0.613). CONCLUSION: This meta-analysis suggests that the VDR FokI polymorphism is associated with susceptibility to RA in European populations. PMID- 26358097 TI - Retrieval of an intra-cardiac embolised very long wire via transhepatic access from a war victim child. AB - We present the case report of a war victim child with severe burn scars, orthopnoea, and dyspnoea due to diffuse pulmonary thromboembolism. During ICU stay, a central venous catheter's 45-mm wire embolised into the heart. The embolised wire was successfully removed via transhepatic access through the creation of an artificial simple snare. PMID- 26358096 TI - Comparison of inherently essential genes of Porphyromonas gingivalis identified in two transposon-sequencing libraries. AB - Porphyromonas gingivalis is a Gram-negative anaerobe and keystone periodontal pathogen. A mariner transposon insertion mutant library has recently been used to define 463 genes as putatively essential for the in vitro growth of P. gingivalis ATCC 33277 in planktonic culture (Library 1). We have independently generated a transposon insertion mutant library (Library 2) for the same P. gingivalis strain and herein compare genes that are putatively essential for in vitro growth in complex media, as defined by both libraries. In all, 281 genes (61%) identified by Library 1 were common to Library 2. Many of these common genes are involved in fundamentally important metabolic pathways, notably pyrimidine cycling as well as lipopolysaccharide, peptidoglycan, pantothenate and coenzyme A biosynthesis, and nicotinate and nicotinamide metabolism. Also in common are genes encoding heat shock protein homologues, sigma factors, enzymes with proteolytic activity, and the majority of sec-related protein export genes. In addition to facilitating a better understanding of critical physiological processes, transposon-sequencing technology has the potential to identify novel strategies for the control of P. gingivalis infections. Those genes defined as essential by two independently generated TnSeq mutant libraries are likely to represent particularly attractive therapeutic targets. PMID- 26358098 TI - Emergence of novel subtypes of Cryptosporidium parvum in calves in Poland. AB - The aim of the study was to identify the Cryptosporidium parvum subtypes circulating in Polish cattle and their distribution in relation to the age and health status of tested animals. In total, 779 fecal samples were obtained from young cattle originating from 237 farms. C. parvum strains were identified at the 18 small-subunit ribosomal RNA (SSU rRNA), COWP, and LIB13 loci and were subsequently analyzed by sequencing at the 60-kDa glycoprotein (GP60) locus for subtype determination. The presence of 71 C. parvum strains belonging to IIa, IId, or IIl subtype families was shown. The strains from the IIa allele family prevailed with IIaA17G1R1, IIaA17G2R1, and IIaA15G2R1 subtypes occurring frequently. Two novel subtypes IIaA10G1R1 and IIlA19R3 were detected for the first time in a bovine host. The highest C. parvum prevalence (22.5 %, confidence interval (CI) = 2.5 %) was observed among the youngest animals up to 2 weeks of age, followed by the prevalence among those aged 2 to 4 weeks (6.6 %, CI = 2.6 %) and then among older cattle (4.9 %, CI = 2.1). The occurrence of diarrhea in animals was associated with the presence of the IIaA16G1R1b subtype, while infections caused by IIaA15G2R1 strains were more likely to be asymptomatic. The geographical distribution of subtypes revealed that strains from the IIa subtype family were detected all over the country frequently compared to the IId and IIl subtypes, the sporadic appearances of which confirmed their endemic occurrence. Subtype analysis revealed the presence of zoonotic strains indicating cattle as a reservoir for human cryptosporidiosis. PMID- 26358099 TI - Effect of anti-hyperlipidemia drugs on the alpha-tocopherol concentration and their potential for murine malaria infection. AB - The current preventions of malaria are protection against mosquito bites and taking chemoprophylactic anti-malarial drugs. However, drug therapies are usually associated with adverse events and emergency of drug-resistant malaria parasites. Previous study showed that host plasma alpha-tocopherol deficiency enhanced resistance against malaria infection in mice. Here, we report a new prevention strategy against malaria by using anti-hyperlipidemia drugs, ezetimibe, berberine, cholestyramine, and probucol to modify the host plasma alpha tocopherol concentration. The drugs were mixed with diet and fed to C57BL/6J mice for 2 weeks. Although all drugs reduced plasma alpha-tocopherol concentration after 2 weeks of feeding, probucol-treated mice showed 90 % reduction and it was the lowest alpha-tocopherol concentration among the four drugs. Ezetimibe, berberine, and combination of ezetimibe and berberine pretreatment for 2 weeks were not effective against infection of Plasmodium yoelii XL17, a lethal strain, for survival and parasitemia in mice. Two-week pretreatment and 1-week treatment after infection of cholestyramine had also no effect on malaria infection. Survival rates of cholestyramine, ezetimibe, and/or berberine treated mice were 0 22 %. However, probucol caused significant decrease in parasitemia and increased in mice survival following 2-week pretreatment and 1-week treatment after infection. All control mice died while all probucol treated mice survived during the course of infection. Thus, probucol which reduced plasma alpha-tocopherol concentration was effective in enhancing the host to resist malaria infection in mice. Our finding indicates that plasma alpha-tocopherol reducing drugs like probucol might be a candidate for beneficial prevention strategy for travelers from malaria-free area. PMID- 26358101 TI - Prevalence of Haemoproteus spp. (Apicomplexa: Haemoproteidae) in tortoises in Brazil and its molecular phylogeny. AB - Captive terrestrial tortoises of the species Chelonoidis carbonaria (n = 17) and Chelonoidis denticulata (n = 37) in the state of Minas Gerais, southeastern Brazil, were examined for hematozoans by using a combination of microscopic and molecular methods. Microscopic examination revealed young intra-erythrocytic forms in blood smears from both species of tortoises. The results of PCR, sequencing, and phylogenetic analysis indicated that these parasites belonged to the Haemoproteus spp., whose observed prevalence was 17.6 % in C. carbonaria and 13.5 % in C. denticulata. Phylogenetic analysis indicated that these sequences formed a clade that was grouped with other sequences of Haemoproteus spp. parasites in birds, separate from the clade formed by Haemoproteus spp. of reptiles. This study expands the information regarding the occurrence and distribution of hemosporidia in turtles and is the first study of blood parasites in C. carbonaria. PMID- 26358100 TI - DNA barcoding and molecular evolution of mosquito vectors of medical and veterinary importance. AB - Mosquitoes (Diptera: Culicidae) are a key threat for millions of people worldwide, since they act as vectors for devastating pathogens and parasites. The standard method of utilisation of morphological characters becomes challenging due to various factors such as phenotypical variations. We explored the complementary approach of CO1 gene-based identification, analysing ten species of mosquito vectors belonging to three genera, Aedes, Culex and Anopheles from India. Analysed nucleotide sequences were found without pseudo genes and indels; they match with high similarity in nucleotide Basic Local Alignment Search Tool (BLASTn) search. The partial CO1 sequence of Anopheles niligricus was the first time record submitted to National Center for Biotechnology Information (NCBI). Mean intra- and interspecies divergence was found to be 1.30 and 3.83 %, respectively. The congeneric divergence was three times higher than the conspecifics. Deep intraspecific divergence was noted in three of the species, and the reason could be explained more accurately in the future by improving the sample size across different locations. The transitional and transversional substitutions were tested individually. Ts and Tv substitutions in all the 1st, 2nd and 3rd codons were estimated to be (0.44, 99.51), (40.35, 59.66) and (59.16, 40.84), respectively. Saturation of the sequences was resolved, since both the Ts and Tv exhibited a linear relationship suggesting that the sequences were not saturated. NJ and ML tree analysis showed that the individuals of the same species clustered together based on the CO1 sequence similarity, regardless of their collection site and geographic location. Overall, this study adds basic knowledge to molecular evolution of mosquito vectors of medical and veterinary importance and may be useful to improve biotechnological tools employed in Culicidae control programmes. PMID- 26358102 TI - Higher prevalence and levels of Nosema ceranae than Nosema apis infections in Canadian honey bee colonies. AB - This study was conducted to determine the prevalence and infection levels of the microsporidia fungi Nosema apis and/or Nosema ceranae in honey bee colonies of two Canadian provinces. Three surveys were conducted in the springs of 2008, 2010 and 2012 and PCR identification of Nosema species were performed in samples from 169 and 181 Ontario colonies and from 76 Alberta colonies that tested positive to Nosema spp. Infection levels of positive colonies were determined by microscopy and analyzed by Nosema spp. Results showed that N. ceranae was the dominant species in all three surveys (prevalence range of 41-91 vs. 4-34 % for N. apis), whereas mixed infections were less frequent than single infections (5-25 %). Infection levels of colonies parasitized by N. ceranae were three to five times higher than those of colonies parasitized by N. apis in the three surveys whereas mixed infections showed the highest spore counts. This is the first field study demonstrating significantly higher infection levels in colonies parasitized with either N. ceranae only or with both, N. ceranae and N. apis, than in colonies parasitized with N. apis only. Taken together, these results suggest that N. ceranae may be more virulent and better adapted than N. apis in cold climates such as Canadian environments. PMID- 26358103 TI - Improving the effectiveness of three essential oils against Aedes aegypti (Linn.) and Anopheles dirus (Peyton and Harrison). AB - Repellency of essential oil extracted from Curcuma longa, Eucalyptus globulus, and Citrus aurantium at various concentrations (5, 10, 15, 20, and 25 %) with and without 5 % vanillin was evaluated against female mosquitoes: Aedes aegypti and Anopheles dirus. The comparisons were made with a commercial chemical repellent (N,N-diethyl-3-methylbenzamide (DEET) 25 % w/w; KOR YOR 15) by arm in cage method. It was found that the essential oils with 5 % vanillin gave the longest lasting period against two mosquitoes as follows: Curcuma longa gave 150 min for Ae. aegypti, 480 min for An. dirus; Eucalyptus globulus gave 144 min for Ae. aegypti, 390 min for An. dirus; and Citrus aurantium gave 120 min for Ae. aegypti, 360 min for An. dirus. The 25 % Curcuma longa essential oil exhibited the best efficiency as equal as a commercial repellent (480 min against An. dirus). Vanillin can extend the period of time in protection against the two mosquitoes. This study indicates the potential uses of the essential oils (Curcuma longa, Eucalyptus globulus, and Citrus aurantium) with vanillin as natural mosquito repellents. PMID- 26358104 TI - The development and implementation of a method using blue mussels (Mytilus spp.) as biosentinels of Cryptosporidium spp. and Toxoplasma gondii contamination in marine aquatic environments. AB - Surveillance monitoring for microbial water quality typically involves collecting single discrete grab samples for analyzing only one contaminant. While informative, current approaches suffer from poor recoveries and only provide a limited snapshot of the microbial contaminants only at the time of collection. To overcome these limitations, bivalves have been proposed as effective biosentinels of water quality particularly for their ability to efficiently concentrate and retain microbial contaminants for long periods of time. In this study, we examined the use of indigenous blue mussels (Mytilus spp.) as biosentinels to monitor for the presence of Toxoplasma gondii and Cryptosporidium water. An efficient method to extract oocyst DNA from various mussel tissues followed by PCR-based detection of these pathogens was developed, which resulted in the detection down to 10 oocysts. This method was then used to conduct a small survey in Point Lobos and Morro Bay, California to determine prevalence T. gondii and Cryptosporidium. Results revealed that mussels from Morro Bay were contaminated with T. gondii (33 %), while mussels from Point Lobos were contaminated with T. gondii (54 %) and Cryptosporidium (26.9 %) oocysts. Phylogenetic analysis using the SSU rRNA gene identified two novel Cryptosporidium parvum-like genotypes. Overall, this study demonstrated the application of using native California Mytilus spp. as biosentinels for pathogen contamination along the central California shorelines. More importantly, T. gondii and Cryptosporidium were found at higher prevalence rates in Morro Bay and in Point Lobos, an area not previously reported to be contaminated with these pathogens. PMID- 26358105 TI - A comparison of four light traps for collecting Culicoides biting midges. AB - Epidemiological analyses of vector-associated diseases such as bluetongue (BT), African horse sickness, or epizootic hemorrhagic disease require substantiated data on the species diversity and activity patterns of vector species. To this end, Spain and Italy implemented extensive Culicoides biting midge monitoring programs since 2000, as several other countries did after the arrival of BT in northern Europe in 2006. The seasonal occurrence, spatial distribution, and abundance of Culicoides species, as the major results of such monitoring programs, are used as parameters for assessing the risk of virus introduction and transmission in a given area. However, the quality of entomological monitoring results fundamentally depends on the collection techniques. In this publication, we describe a Latin Square design trial carried out in Germany under field conditions in 2009/2010 to compare the efficacy of four commonly used light baited/suction traps in collecting Culicoides. A total of 2651 Culicoides were caught over 18 nights. In both years, the Onderstepoort and BG-Sentinel traps caught significantly more Culicoides than the Rieb and the CDC trap. Most specimens were caught by the Onderstepoort trap (1246, i.e., 76 % in 2009 and 819, i.e., 82 % in 2010). Most were classified as midges of the Culicoides obsoletus group. PMID- 26358106 TI - The Bottleneck in Genetic Testing. PMID- 26358107 TI - Unveiling the Mechanism of Coronary Metabolic Vasodilation: Voltage-Gated Potassium Channels and Hydrogen Peroxide. PMID- 26358108 TI - A New Pathway for Sympathetic Cardioprotection in Heart Failure. PMID- 26358109 TI - Cell-Based Gene Therapy in Pulmonary Arterial Hypertension: Journeys in Translational Medicine. PMID- 26358110 TI - Joseph C. Wu: Envisioning Personalized Medicine and Clinical Trials in a Dish. PMID- 26358112 TI - Notice of Retraction. PMID- 26358111 TI - Recent Developments in Heart Failure. PMID- 26358113 TI - Transgenic animals and genetic engineering techniques. Nantes, France, 2-3 July, 2015. PMID- 26358114 TI - Genome instability model of metastatic neuroblastoma tumorigenesis by a dictionary learning algorithm. AB - BACKGROUND: Metastatic neuroblastoma (NB) occurs in pediatric patients as stage 4S or stage 4 and it is characterized by heterogeneous clinical behavior associated with diverse genotypes. Tumors of stage 4 contain several structural copy number aberrations (CNAs) rarely found in stage 4S. To date, the NB tumorigenesis is not still elucidated, although it is evident that genomic instability plays a critical role in the genesis of the tumor. Here we propose a mathematical approach to decipher genomic data and we provide a new model of NB metastatic tumorigenesis. METHOD: We elucidate NB tumorigenesis using Enhanced Fused Lasso Latent Feature Model (E-FLLat) modeling the array comparative chromosome hybridization (aCGH) data of 190 metastatic NBs (63 stage 4S and 127 stage 4). This model for aCGH segmentation, based on the minimization of functional dictionary learning (DL), combines several penalties tailored to the specificities of aCGH data. In DL, the original signal is approximated by a linear weighted combination of atoms: the elements of the learned dictionary. RESULTS: The hierarchical structures for stage 4S shows at the first level of the oncogenetic tree several whole chromosome gains except to the unbalanced gains of 17q, 2p and 2q. Conversely, the high CNA complexity found in stage 4 tumors, requires two different trees. Both stage 4 oncogenetic trees are marked diverged, up to five sublevels and the 17q gain is the most common event at the first level (2/3 nodes). Moreover the 11q deletion, one of the major unfavorable marker of disease progression, occurs before 3p loss indicating that critical chromosome aberrations appear at early stages of tumorigenesis. Finally, we also observed a significant (p = 0.025) association between patient age and chromosome loss in stage 4 cases. CONCLUSION: These results led us to propose a genome instability progressive model in which NB cells initiate with a DNA synthesis uncoupled from cell division, that leads to stage 4S tumors, primarily characterized by numerical aberrations, or stage 4 tumors with high levels of genome instability resulting in complex chromosome rearrangements associated with high tumor aggressiveness and rapid disease progression. PMID- 26358115 TI - Is there an association between invasive lobular carcinoma of the breast and a family history of gastric cancer? AB - CDH1 gene mutations have been found to be associated with diffuse type gastric cancer and invasive lobular carcinoma (ILC) of the breast. To the best of our knowledge, this is the only study relating a family history of gastric cancer to ILC of the breast. We conducted a retrospective study comparing the family history of malignancies in patients with invasive ductal carcinoma (IDC) of the breast and ILC treated in our Medical Center. The comparison was evaluated in both types of breast cancer groups, dividing the patients into two age groups, <50 and >=50 years. One thousand one hundred and sixty-seven patients with IDC and ILC entered the study. A family history of malignancies was reported in 21.6 % of patients with IDC as opposed to 37.8 % of patients with ILC (P < 0.001). A history of gastric cancer was reported in 7.2 % in the ILC group as compared to 2.3 % in the IDC group, P < 0.008. A family history of breast cancer was more common in the ILC group as opposed to the IDC group, 18 versus 8.1 % respectively, P = 0.002 and persisted in both age groups. We conclude that a family history of malignancies in first degree relatives is more common in patients with ILC than IDC and that there is a significant association between a family history of gastric cancer and ILC. PMID- 26358116 TI - Disease profiles of detainees in the Canton of Vaud in Switzerland: gender and age differences in substance abuse, mental health and chronic health conditions. AB - BACKGROUND: Literature on the disease profile of prisoners that differentiates by age and gender remains sparse. This study aimed to describe the health of correctional inmates in terms of substance abuse problems and mental and somatic health conditions, and compare it by gender and age. METHODS: This study examined cross-sectional data from the Canton of Vaud in Switzerland on the health conditions of detainees who were in prison on January 1, 2011 or entered prison in 2011. Health conditions validated by physician examination were reported using the International Classification of Diseases (ICD) version 10. The analyses were descriptive by groups of prisoners: the entire sample (All), Men, Older adults and Women. RESULTS: A total of 1,664 individuals were included in the analysis. Men comprised 91.5 % of the sample and had a mean age of 33 years. The other 8.5 % were women and had an average age of 39. Older adults (i.e., age 50 and older) represented 7 % of the total sample. Overall, 80 % of inmates were non-Swiss citizens, but the proportion of Swiss prisoners was higher among the older adults (51 %) and women (29 %). Overall, 41 % of inmates self-reported substance abuse problems. Of those, 27 % were being treated by psychiatrists for behavioral disorders related to substance abuse. Chronic infectious diseases were found in 9 % of the prison population. In addition, 27 % of detainees suffered from serious mental health conditions. Gender and age had an influence on the disease profile of this sample: compared to the entire prison population, the older inmates were less likely to misuse illegal drugs and to suffer from communicable infections but exhibited more problems with alcohol and a higher burden of chronic health conditions. Female prisoners were more disposed to mental health problems (including drug abuse) and infectious diseases. In terms of chronic diseases, women suffered from the same conditions as men, but the diseases were more prevalent in women. CONCLUSION: It is important to understand the different disease profiles of prisoners by gender and age, as it helps identify the needs of different groups and tailor age-and gender-specific interventions. PMID- 26358117 TI - Antricoccus suffuscus gen. nov., sp. nov., isolated from a natural cave. AB - A novel actinobacterium, designated strain C4-31T, was isolated from soil collected from a cave. Cells were aerobic, Gram-reaction-positive, oxidase negative, catalase-positive and non-motile cocci. Comparison of 16S rRNA gene sequences showed that the organism occupied a distinct phylogenetic position within the suborder Frankineae, with sequence similarity values of less than 93.2 % to members of this suborder. The diagnostic diamino acid in the cell-wall peptidoglycan was meso-diaminopimelic acid. The major menaquinone was MK-9(H4). The polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol, phosphatidylinositol mannoside, an unknown aminophospholipid and an unknown phospholipid. The major fatty acids were iso-C16 : 0, C17 : 1omega6c and C16 : 0. The G+C content of the DNA was 62.8 mol%. On the basis of morphological and chemotaxonomic data as well as phylogenetic evidence, strain C4-31T ( = KCTC 39556T = DSM 100065T) is considered to represent the type strain of a novel species of a new genus in the suborder Frankineae, for which the name Antricoccus suffuscus gen. nov., sp. nov. is proposed. PMID- 26358118 TI - Enhancing the evaluation of pathogen transmission risk in a hospital by merging hand-hygiene compliance and contact data: a proof-of-concept study. AB - BACKGROUND: Hand-hygiene compliance and contacts of health-care workers largely determine the potential paths of pathogen transmission in hospital wards. We explored how the combination of data collected by two automated infrastructures based on wearable sensors and recording (1) use of hydro-alcoholic solution and (2) contacts of health-care workers provide an enhanced view of the risk of transmission events in the ward. METHODS: We perform a proof-of-concept observational study. Detailed data on contact patterns and hand-hygiene compliance of health-care workers were collected by wearable sensors over 12 days in an infectious disease unit of a hospital in Marseilles, France. RESULTS: 10,837 contact events among 10 doctors, 4 nurses, 4 nurses' aids and 4 housekeeping staff were recorded during the study. Most contacts took place among medical doctors. Aggregate contact durations were highly heterogeneous and the resulting contact network was highly structured. 510 visits of health-care workers to patients' rooms were recorded, with a low rate of hand-hygiene compliance. Both data sets were used to construct histories and statistics of contacts informed by the use of hydro-alcoholic solution, or lack thereof, of the involved health-care workers. CONCLUSIONS: Hand-hygiene compliance data strongly enrich the information concerning contacts among health-care workers, by assigning a 'safe' or 'at-risk' value to each contact. The global contact network can thus be divided into 'at-risk' and 'safe' contact networks. The combined data could be of high relevance for outbreak investigation and to inform data-driven models of nosocomial disease spread. PMID- 26358119 TI - Herbaspirillum sp. strain GW103 alleviates salt stress in Brassica rapa L. ssp. pekinensis. AB - Mutual interactions between plant and rhizosphere bacteria facilitate plant growth and reduce risks of biotic and abiotic stresses. The present study demonstrates alleviation of salt stress in Brassica rapa L. ssp. perkinensis (Chinese cabbage) by Herbaspirillum sp. strain GW103 isolated from rhizosphere soil of Phragmites australis. The strain was capable of producing plant beneficial factors, such as auxin, siderophore, and 1-aminocylopropane-1 carboxylic acid deaminase. Treatment of strain GW103 on Chinese cabbage under salt stress increased K(+)/Na(+) ratio in roots generating balance in the ratio of ion homeostasis and consequently contributed to the increase of biomass. In addition, root colonization potential of the strain was observed by green fluorescent protein (GFP)-tagging approach. These results strongly suggest the beneficial impact of strain GW103 by inducing the alleviation of salt stress and development of stress tolerance in Chinese cabbage via plant-microbe interaction. PMID- 26358120 TI - Preoperative Regular Diet of 900 kcal/day vs Balanced Energy High-Protein Formula vs Immunonutrition Formula: Effect on Preoperative Weight Loss and Postoperative Pain, Complications and Analytical Acute Phase Reactants After Laparoscopic Sleeve Gastrectomy. AB - BACKGROUND: Between 2 and 8 weeks before surgery, most bariatric surgery groups establish strict dietary treatments with a total caloric intake of less than 1,000 kcal/day in order to maximize weight loss during this period of time. METHODS: A prospective randomized clinical trial of all the patients undergoing laparoscopic sleeve gastrectomy (LSG) was performed. Patients were randomly assigned into 3 groups: those patients receiving a preoperative regular diet of 900 kcal/day (group 1), those receiving a preoperative balanced energy high protein formula (group 2) and those receiving preoperative Immunonutrition (group 3). Preoperative weight loss, postoperative pain, complications and analytical acute phase reactants were investigated. RESULTS: Sixty patients were included in the study, 20 in each group. Preoperative excess weight loss was 7.7 % in group 1, 12.3 % in group 2 and 15.3 % in group 3 (p = 0.014). Median postoperative pain was 3.5 in group 1, 3 in group 2 and 2 in group 3 (p = 0.048). C-reactive protein determined 24 h after surgery was significantly lower in group 3 than in the other groups. AST and ALT values were significantly lower in group 3 than in the other groups, without significant differences between groups 1 and 2. CONCLUSIONS: Preoperative diet with Immunonutrition formulas during 2 weeks achieves a greater preoperative weight loss, lower postoperative pain and lower values of CRP and liver enzymes than high-protein formulas or regular diet, all of them with similar caloric intake. PMID- 26358122 TI - Modification of unilateral otolith responses following spaceflight. AB - The aim of the study was to resolve the issue of spaceflight-induced, adaptive modification of the otolith system by measuring unilateral otolith responses in a pre- versus post-flight design. The study represents the first comprehensive approach to examining unilateral otolith function following space flight. Ten astronauts participated in unilateral otolith function tests three times preflight and up to four times after Shuttle flights from landing day through the subsequent 10 days. During unilateral centrifugation, utricular function was examined by the perceptual changes reflected by the subjective visual vertical (SVV) and the otolith-mediated ocular counter-roll, designated as utriculo-ocular response (UOR). Unilateral saccular reflexes were recorded by measurement of collic vestibular evoked myogenic potentials (cVEMP). The findings demonstrate a general increase in interlabyrinth asymmetry of otolith responses on landing day relative to preflight baseline, with subsequent reversal in asymmetry within 2-3 days. Recovery to baseline levels was achieved within 10 days. This fluctuation in asymmetry was consistent for the utricle tests (SVV and UOR) while apparently stronger for SVV. A similar asymmetry was observed during cVEMP testing. In addition, the results provide initial evidence of a dominant labyrinth. The findings require reconsideration of the otolith asymmetry hypothesis; in general, on landing day, the response from one labyrinth was equivalent to preflight values, while the other showed considerable discrepancy. The finding that one otolith response can return to one-g level within hours after re-entry while the other takes considerably longer demonstrates the importance of considering the otolith response as a result of both peripheral and associated central neural processing. PMID- 26358123 TI - Observing functional actions affects semantic processing of tools: evidence of a motor-to-semantic priming. AB - Recent evidence shows that activation of motor information can favor identification of related tools, thus suggesting a strict link between motor and conceptual knowledge in cognitive representation of tools. However, the involvement of motor information in further semantic processing has not been elucidated. In three experiments, we aimed to ascertain whether motor information provided by observation of actions could affect processing of conceptual knowledge about tools. In Experiment 1, healthy participants judged whether pairs of tools evoking different functional handgrips had the same function. In Experiment 2 participants judged whether tools were paired with appropriate recipients. Finally, in Experiment 3 we again required functional judgments as in Experiment 1, but also included in the set of stimuli pairs of objects having different function and similar functional handgrips. In all experiments, pictures displaying either functional grasping (aimed to use tools) or structural grasping (just aimed to move tools independently from their use) were presented before each stimulus pair. The results demonstrated that, in comparison with structural grasping, observing functional grasping facilitates judgments about tools' function when objects did not imply the same functional manipulation (Experiment 1), whereas worsened such judgments when objects shared functional grasp (Experiment 3). Instead, action observation did not affect judgments concerning tool-recipient associations (Experiment 2). Our findings support a task-dependent influence of motor information on high-order conceptual tasks and provide further insights into how motor and conceptual processing about tools can interact. PMID- 26358124 TI - Contralateral conditioning to the soleus H-reflex as a function of age and physical activity. AB - Coordination between ipsilateral and contralateral muscles of the lower limbs has a critical role in movement control. However, the roles that aging and physical activity have in maintaining bilateral coordination are understudied. The aim of this study was to examine the roles of physical activity and age on pathways between the soleus and tibialis anterior muscles. Fourteen young and 14 older subjects (7 active, 7 sedentary) participated. A Hoffmann (H)-reflex was elicited in the ipsilateral soleus following a conditioning stimulus to the contralateral common peroneal nerve at differing intervals (25-300 ms). Significant H-reflex facilitation from the control value was observed for the sedentary group at the 50-ms (28.7 %), 75-ms (24.5 %), and 150-ms (34.0 %) intervals when compared with the physically active group. There were also significant differences between the young and older groups. Results demonstrated differences in soleus H-reflex excitability as a result of contralateral conditioning and highlighted the influence of age and physical activity in maintaining these neural pathways. PMID- 26358125 TI - Attention is required for the perceptual integration of action object pairs. AB - Previous studies have demonstrated that functionally related objects are perceptually grouped during visual identification if they are depicted as if interacting with each other (Green and Hummel in J Exp Psychol Hum Percept Perform 32(5):1107-1119, 2006). However, it is unclear whether this integration requires attention or occurs pre-attentively. Here, we used a divided-attention task with variable attentional load to address this question. Participants matched a word label to a target object that was immediately preceded by a briefly presented, task-irrelevant tool that was either functionally related or unrelated to the word label (e.g., axe | "log" or hammer | "log"). The tool was either positioned to interact with the target object or faced away from it. The amount of attention available to process the tool was manipulated by asking participants to make a concurrent perceptual discrimination of varying difficulty on a surrounding frame stimulus. The previously demonstrated advantage for the related-and-interacting condition was replicated under conditions of no or low attentional load. This benefit disappeared under high competing attentional load, indicating that attention is required to integrate functionally related objects together into a single perceptual unit. PMID- 26358126 TI - How does visuospatial attention modulate motor preparation during gait initiation? AB - Gait initiation is an automatized motor program that is preceded by anticipatory postural adjustments (APAs). These adjustments create the propulsive forces required to reach the steady-state gait at the end of the first step and can be studied by the displacement of the centre of pressure. The objective of this study was to demonstrate that APAs can be modulated by visuospatial attentional processes prior to motor execution. An adaptation of the Posner paradigm was used to assess attention during step initiation. Twelve healthy subjects performed a gait initiation task under three conditions: a no-cue condition (the control experiment), a double-cue condition (alerting attention) and a single-cue condition (orienting attention). The kinetic and kinematic parameters of the APAs and step initiation were recorded. The time to step initiation was significantly shorter in the alerting condition than in the control condition. This effect was associated with the earlier occurrence of APAs. Orienting condition also had an effect and was associated with the modulation of APA errors (defined as a contralateral shift of the CoP on the cue side before corrective shifting to the target side). Behavioural measurements (such as postural preparation of step initiation) may reflect the interaction between attention and locomotion. Our results show that the different components of attention each have a specific influence on step initiation parameters. PMID- 26358127 TI - Rubber hand presentation modulates visuotactile interference effect especially in persons with high autistic traits. AB - Persons with high autistic traits showed diverse reactions as to their multisensory integration, whereas neurotypical persons adequately integrate visual and tactile information. Successive visual stimuli sometimes interfere ordering of successive tactile stimuli. Presentation of a hand-shaped object would affect the interference. Besides, its associations with autistic traits have not been reported. Here, we investigated the effect of a rubber hand presentation on interferences to tactile temporal order judgment by successive visual stimuli. We also investigated whether individual differences associated with autistic traits. A rubber hand was placed palm down in front of the participant in one condition, while in other conditions, it was inverted or was not presented. Participants were required to judge the temporal order of tactile stimuli presented to the index finger and ring finger of their unseen right hand, and needed to ignore the visual stimuli placed on the corresponding fingers of the rubber hand. When incongruent visual stimuli were delivered along with presentation of the rubber hand, the participant's judgment was notably reversed. In contrast, the degree of reversals significantly decreased when the rubber hand was not presented or presented in an inverted direction. Additionally, we found that participants with high autistic traits tended to show large reversal with the rubber hand presentation, while they showed small reversal when the rubber hand was inverted. Our results suggest that rubber hand corresponding to one's own hand facilitates visuotactile interference. Furthermore, autistic traits may affect the integration of visuotactile inputs when the rubber hand is presented. PMID- 26358128 TI - Optokinetic circular vection: a test of visual-vestibular conflict models of vection nascensy. AB - The propensity to experience circular vection (the illusory perception of self turning evoked by a rotating scene, CV) as reflected by its onset latency exhibits considerable interindividual variation. Models of CV nascensy have linked this delay to the time it takes the visual-vestibular conflict to disappear. One line of these "conflict models" (Zacharias and Young in Exp Brain Res 41:159-171, 1981) predicts that, across individuals, CV latency (CVL) correlates positively with the vestibular time constant (TC) and negatively with the vestibular motion detection threshold (vTHR). A second type of models (Mergner et al. in Arch Ital Biol 138:139-166, 2000) predicts only an increase in CVL with TC. We here examine which of these predictions can be experimentally substantiated. Also, we ask whether the relative weight W O of the optokinetic contribution to the perception of real self-turning could also be a factor influencing CVL. We conducted 5 experiments in 29 subjects measuring: (1) CVL, (2) the TCs of velocity perception and of accompanying nystagmus during rotation in darkness and (3) likewise for displacement perception, (4) vTHR, and (5) W O as revealed by discordant visual-vestibular stimulation. CVL correlated with the nystagmus TC recorded during velocity estimation but with none of the other vestibular TCs nor with vTHR. Confirming earlier findings, CVL shortened with rising scene velocity. Finally, CVL correlated inversely with W O: the larger an individual's optokinetic weight, the shorter was his CVL. Taken together, our data favour the second type of models which invoke an antagonism between CV inhibition by the optokinetic-vestibular conflict and disinhibition by optokinetic stimulation. Idiosyncratic factors appear to strongly modulate the balance between inhibition and disinhibition, thus increasing CVL variability and obscuring the expected relation between CVL and TC. PMID- 26358129 TI - Discontinuing Pneumocystis jirovecii Pneumonia Prophylaxis in HIV-Infected Patients With a CD4 Cell Count <200 cells/mm3. AB - OBJECTIVE: To review the evidence for discontinuing primary and secondary Pneumocystis jirovecii pneumonia (PJP) prophylaxis in HIV-infected patients with a CD4 count <200 cells/mm(3). DATA SOURCES: We conducted a literature search in MEDLINE, EMBASE, Cochrane Library, Google Scholar, and the International Aids Society Library (up to August 2015) using the following key search terms: Pneumocystis jirovecii, pneumonia, human immunodeficiency virus, primary prophylaxis, secondary prophylaxis, and discontinuation. STUDY SELECTION AND DATA EXTRACTION: All English-language studies that evaluated discontinuation of primary and/or secondary PJP prophylaxis in HIV-infected patients with CD4 count <200 cells/mm(3) were included. DATA SYNTHESIS: Five studies were identified, which varied in design, sample size, outcomes, and duration of follow-up. Three studies examined discontinuation of primary and secondary PJP prophylaxis; 1 study evaluated discontinuing primary PJP prophylaxis; and 1 study evaluated stopping secondary PJP prophylaxis. Two out of the 5 studies pooled data for all opportunistic infections. Overall, there was a low incidence of PJP among HIV infected patients who discontinued primary PJP prophylaxis and were well controlled on antiretroviral therapy (ART). CONCLUSIONS: Discontinuation of primary PJP prophylaxis appears to be safe in patients on combination ART with a suppressed HIV viral load and a CD4 count >100 cells/mm(3). Additional data are needed to support the safety of discontinuing secondary PJP prophylaxis. Decisions to discontinue PJP prophylaxis in patients with a CD4 count <200 cells/mm(3) should be done on an individual patient basis, taking into consideration clinical factors, including ongoing adherence to ART. PMID- 26358131 TI - Chronic tubo-ovarian abscess complicated by hepatic portal venous gas. AB - 44-year-old female with massive chronic tubo-ovarian abscess complicated by hepatic portal venous gas (HPVG). She presented to the emergency department of our hospital with a diffusely tender abdomen and 2 weeks history of frequent non bloody loose stools. She had a relevant past medical history of poorly controlled type 1 diabetes mellitus and hypertension. Abdominal computerized tomography revealed massive right abdomino-pelvic mass measuring 17.6 * 12.1 * 20 cm and diffuse HPVG. Patient underwent exploratory laparotomy, salpingo-oophorectomy, peritoneal lavage with antibiotics and treatment for septic shock. No similar case known to us has been reported in the literature previously. PMID- 26358130 TI - Post-transcriptional Mechanisms Contribute Little to Phenotypic Variation in Snake Venoms. AB - Protein expression is a major link in the genotype-phenotype relationship, and processes affecting protein abundances, such as rates of transcription and translation, could contribute to phenotypic evolution if they generate heritable variation. Recent work has suggested that mRNA abundances do not accurately predict final protein abundances, which would imply that post-transcriptional regulatory processes contribute significantly to phenotypes. Post-transcriptional processes also appear to buffer changes in transcriptional patterns as species diverge, suggesting that the transcriptional changes have little or no effect on the phenotypes undergoing study. We tested for concordance between mRNA and protein expression levels in snake venoms by means of mRNA-seq and quantitative mass spectrometry for 11 snakes representing 10 species, six genera, and three families. In contrast to most previous work, we found high correlations between venom gland transcriptomes and venom proteomes for 10 of our 11 comparisons. We tested for protein-level buffering of transcriptional changes during species divergence by comparing the difference between transcript abundance and protein abundance for three pairs of species and one intraspecific pair. We found no evidence for buffering during divergence of our three species pairs but did find evidence for protein-level buffering for our single intraspecific comparison, suggesting that buffering, if present, was a transient phenomenon in venom divergence. Our results demonstrated that post-transcriptional mechanisms did not contribute significantly to phenotypic evolution in venoms and suggest a more prominent and direct role for cis-regulatory evolution in phenotypic variation, particularly for snake venoms. PMID- 26358132 TI - Collaborative science in the next-generation sequencing era: a viewpoint on how to combine exome sequencing data across sites to identify novel disease susceptibility genes. AB - The purpose of this article is to inform readers about technical challenges that we encountered when assembling exome sequencing data from the 'Simplifying Complex Exomes' (SIMPLEXO) consortium-whose mandate is the discovery of novel genes predisposing to breast and ovarian cancers. Our motivation is to share these obstacles-and our solutions to them-as a means of communicating important technical details that should be discussed early in projects involving massively parallel sequencing. PMID- 26358133 TI - Synoptic operative reports for spinal cord injury patients as a tool for data quality. AB - The advent of synoptic operative reports has revolutionized how clinical data are captured at the time of care. In this article, an electronic synoptic operative report for spinal cord injury was implemented using interoperable standards, HL7 and Systematized Nomenclature of Medicine-Clinical Terms. Subjects (N = 10) recruited for a pilot study completed recruitment and feedback questionnaires, and produced both an electronic synoptic operative report for spinal cord injury report and a dictated narrative operative report for an actual patient case. Results indicated heterogeneity by subjects in access and use of electronic sources of patient data. Feedback questionnaire results confirmed that subjects were comfortable using both methods for data entry of operative reports, and that some were unable to find the diagnosis terms they needed in electronic synoptic operative report for spinal cord injury. Data quality improved. Electronic synoptic operative report for spinal cord injury reports were more complete (95.26%) than dictated (80%) for all subjects. An accuracy assessment, which considered usability for secondary data use, was conducted and the electronic synoptic operative report for spinal cord injury was demonstrated to improve accuracy. PMID- 26358134 TI - Low rates of breast feeding in India require national action, says report. PMID- 26358135 TI - Role of JNK and NF-kappaB in mediating the effect of combretastatin A-4 and brimamin on endothelial and carcinoma cells. AB - PURPOSE: The 4,5-diarylimidazole brimamin is an analog of the natural vascular disrupting agent combretastatin A-4 (CA-4) with improved water solubility, tolerance by animals and efficacy in multidrug-resistant tumors. Here, we aimed at identifying the major mechanisms underlying the in vitro and in vivo actions of brimamin on endothelial and carcinoma cells, including vascularization. METHODS: The contribution of specific signaling kinases to the effects of brimamin on cytoskeleton organization and the viability and differentiation of endothelial cells was assessed by MTT and tube formation assays in the presence or absence of specific kinase inhibitors. Changes in DNA affinity and expression of NF-kappaB in endothelial and carcinoma-derived cells and their solid tumors (xenografts) treated with brimamin were ascertained by electrophoretic mobility shift assays and Western blotting. The anti-vascular effect of brimamin in solid tumors was verified by CD31 immunostaining. RESULTS: We found that brimamin can inhibit tubulin polymerization and cause a reorganization of F-actin in Ea.hy926 endothelial cells. Its inhibitory effect on tube formation was found to depend on functional Rho kinase and JNK. JNK inhibition was found to suppress the induction of endothelial cell apoptosis by brimamin. In CA-4-refractory human BxPC-3 pancreas carcinoma-derived and triple-negative MDA-MB-231 breast carcinoma derived cells brimamin was found to inhibit growth and to induce apoptosis at low nanomolar concentrations by blocking NF-kappaB activation in a dose-dependent manner. Brimamin was also found to reduce the in vivo growth rate and vascularization of MDA-MB-231 xenografts in mice. Residual tumor cells of these treated xenografts showed a relatively low expression of the p65 subunit of NF kappaB. CONCLUSIONS: Our data indicate that cellular JNK and Rho kinase activities are crucial for the cytotoxic and cytoskeleton reorganizing effects of brimamin on endothelial cells. In addition, we found that in resistant carcinoma cells and xenografts brimamin can induce down-regulation of anti-apoptotic NF kappaB expression and signaling. Its chemical properties and efficacy against clinically relevant cancer entities make brimamin a promising candidate vascular disrupting agent. PMID- 26358136 TI - Completeness of the circle of Willis and risk of ischemic stroke in patients without cerebrovascular disease. AB - INTRODUCTION: We investigated circle of Willis (CoW) completeness in relation to the risk of future ischemic stroke in patients without prior cerebrovascular disease. METHODS: We included 976 patients with atherosclerotic disease, but no previous TIA/stroke, from the Second Manifestations of ARTerial disease (SMART) study. All patients underwent MR angiography of the CoW. Cox regression was used to determine whether anterior CoW completeness (anterior communicating artery or A1 segments) and posterior CoW completeness (posterior communicating arteries or P1 segments) were related to future stroke, and whether CoW completeness influenced the relation between internal carotid artery (ICA) stenosis/occlusion and future stroke. RESULTS: Thirty patients (3.1 %) had ischemic stroke after 9.2 +/- 3.0 years of follow-up. Twenty-four patients (80 %) had anterior circulation stroke. An incomplete anterior CoW was related to future anterior circulation stroke (HR 2.8 (95 % CI 1.3-6.3); p = 0.01), whereas a one-sided and two-sided incomplete posterior CoW were not (HR 2.2 (95 % CI 0.7-7.1; p = 0.19) and 1.9 (95 % CI 0.6-5.9; p = 0.29), respectively). In stratified analyses, patients with an incomplete anterior CoW had the highest risk of future anterior circulation stroke when they also had a one-sided (HR 7.0 (95 % CI 1.3-38.2; p = 0.02)) or two-sided incomplete posterior CoW (HR 5.4 (95 % CI 1.0-27.8; p = 0.04). CoW completeness did not change the relation between asymptomatic ICA stenosis/occlusion and future ischemic stroke (p = 0.68). CONCLUSIONS: An incomplete anterior CoW combined with an incomplete posterior CoW is related to future anterior circulation stroke. CoW completeness has no large effect on the relation between asymptomatic ICA stenosis/occlusion and future stroke. PMID- 26358137 TI - Adult vertebrate behavioural aquatic toxicology: Reliability and validity. AB - Current advances in the ability to assay adult aquatic vertebrate behaviour are potentially very useful to aquatic toxicologists wishing to characterise the effects of pollutants on behaviour, cognition or neurodevelopment. This review considers two specific challenges faced by researchers wishing to exploit these technologies: maximising reliability and validity. It will suggest two behavioural procedures, with the potential for automation and high-throughput implementation, which can be used to measure social cohesion and anxiety, two areas of interest in behavioural aquatic toxicology. In addition, the review will make recommendations about how these procedures (and others) could be carried out to maximise reliability and validity. PMID- 26358138 TI - Antifibrotic mechanism of deferoxamine in concanavalin A induced-liver fibrosis: Impact on interferon therapy. AB - Iron-overload is a well-known factor of hepatotoxicity and liver fibrosis, which found to be a common finding among hepatitis C virus patients and related to interferon resistance. We aimed to elucidate the potential antifibrotic effect of deferoxamine; the main iron chelator, and its additional usefulness to interferon based therapy in concanavalin A-induced immunological model of liver fibrosis. Rats were treated with deferoxamine and/or pegylated interferon-alpha for 6 weeks. Hepatotoxicity indices, oxidative stress, inflammatory and liver fibrosis markers were assessed. Concanavalin A induced a significant increase in hepatotoxicity indices and lipid peroxidation accompanied with a significant depletion of total antioxidant capacity, glutathione level and superoxide dismutase activity. Besides, it increased CD4(+) T-cells content and the downstream inflammatory cascades, including NF-kappaB, TNF-alpha, iNOS, COX-2, IL 6 and IFN-gamma. Furthermore, alpha-SMA, TGF-beta1 and hydroxyproline were increased markedly, which confirmed by histopathology. Treatment with either deferoxamine or pegylated interferon-alpha alone reduced liver fibrosis markers significantly and improved liver histology. However, some of the hepatotoxicity indices and oxidative stress markers did not improve upon pegylated interferon alpha treatment alone, besides the remarkable increase in IL-6. Combination therapy of deferoxamine with pegylated interferon-alpha further improved all previous markers, ameliorated IL-6 elevation, as well as increased hepcidin expression. In conclusion, our study provides evidences for the potent antifibrotic effects of deferoxamine and the underlying mechanisms that involved attenuating oxidative stress and subsequent inflammatory cascade, as well as the production of profibrogenic factors. Addition of deferoxamine to interferon regimen for HCV patients may offer a promising adjuvant modality to enhance therapeutic response. PMID- 26358139 TI - Current biomarkers for diagnosing of prostate cancer. AB - Prostate cancer (PCa) is mostly detected by prostate-specific antigen (PSA) as one of the most widely used tumor markers. But PSA is limited with its low specificity. The prostate health index (phi) can improve specificity over percent free and total PSA and correlates with aggressive cancer. The urinary PCA3 also shows its utility to detect PCa but its correlation with aggressiveness and the low sensitivity at high values are limitations. While the detection of alterations of the androgen-regulated TMPRSS2 and ETS transcription factor genes in tissue of ~50% of all PCa patients was one research milestone, the urinary assay should only be used in combination with PCA3. Both US FDA-approved markers phi and PCA3 perform equally. PMID- 26358141 TI - B-MIC: An Ultrafast Three-Level Parallel Sequence Aligner Using MIC. AB - Sequence alignment is the central process for sequence analysis, where mapping raw sequencing data to reference genome. The large amount of data generated by NGS is far beyond the process capabilities of existing alignment tools. Consequently, sequence alignment becomes the bottleneck of sequence analysis. Intensive computing power is required to address this challenge. Intel recently announced the MIC coprocessor, which can provide massive computing power. The Tianhe-2 is the world's fastest supercomputer now equipped with three MIC coprocessors each compute node. A key feature of sequence alignment is that different reads are independent. Considering this property, we proposed a MIC oriented three-level parallelization strategy to speed up BWA, a widely used sequence alignment tool, and developed our ultrafast parallel sequence aligner: B MIC. B-MIC contains three levels of parallelization: firstly, parallelization of data IO and reads alignment by a three-stage parallel pipeline; secondly, parallelization enabled by MIC coprocessor technology; thirdly, inter-node parallelization implemented by MPI. In this paper, we demonstrate that B-MIC outperforms BWA by a combination of those techniques using Inspur NF5280M server and the Tianhe-2 supercomputer. To the best of our knowledge, B-MIC is the first sequence alignment tool to run on Intel MIC and it can achieve more than fivefold speedup over the original BWA while maintaining the alignment precision. PMID- 26358140 TI - CCL3 and CCL4 are biomarkers for B cell receptor pathway activation and prognostic serum markers in diffuse large B cell lymphoma. AB - B cell receptor (BCR) signalling is an important pathway in diffuse large B cell lymphoma (DLBCL). In response to BCR triggering, normal and malignant B cells secrete the chemokines CCL3 and CCL4 to attract accessory cells to the tissue microenvironment. We measured CCL3 and CCL4 serum concentrations in 102 patients with newly diagnosed DLBCL by enzyme-linked immunosorbent assay, investigated their prognostic impact and validated our findings in an independent cohort of 51 patient samples. We also tested CCL3 and CCL4 secretion by DLBCL cells, and the influence of BTK inhibitors on the secretion of these chemokines. High CCL3 (>=40 pg/ml) serum concentrations correlated with higher international prognostic index, lactate dehydrogenase and beta2 microglobulin, as did CCL4 (>=180 pg/ml) with advanced Ann Arbor stages. High CCL3 levels correlated with significantly shorter progression-free and overall survival. The in vitro studies demonstrated that activated B cell-like, but not germinal centre B cell-like DLBCL cells, secrete high levels of CCL3 and CCL4 after BCR triggering, which was exquisitely sensitive to BCR pathway inhibition. These findings support CCL3 and CCL4 protein concentrations as biomarkers for BCR pathway activation and prognosis in DLBCL. PMID- 26358142 TI - Dressings and securement devices for central venous catheters (CVC). AB - BACKGROUND: Central venous catheters (CVCs) play a vital role in the management of acute and chronic illness. Dressings and securement devices must ensure CVCs do not dislodge or fall out, provide a barrier protection from microbial colonisation and infection, and be comfortable for the patient. There is a large range of dressing and securement products available for clinicians to use. OBJECTIVES: To compare the available dressing and securement devices for CVCs, in terms of catheter-related bloodstream infection (BSI), catheter colonisation, entry- and exit-site infection, skin colonisation, skin irritation, failed catheter securement, dressing condition and mortality. SEARCH METHODS: In June 2015 we searched: The Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL); The Database of Abstracts of Reviews of Effects (DARE); NHS Economic Evaluation Database (NHSEED); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; EBSCO CINAHL; six clinical trial registries and reference lists of identified trials. There were no restrictions based on language or date of publication or study setting. SELECTION CRITERIA: We included randomised controlled trials that evaluated the effects of dressing and securement devices for CVCs. All types of CVCs were included, i.e. short- and long-term CVCs, tunnelled and non-tunnelled, port-a-caths, haemodialysis catheters, and peripherally-inserted central catheters (PICCs). DATA COLLECTION AND ANALYSIS: We used standard Cochrane Collaboration methods including independent review of titles and abstracts for relevance, data extraction, and risk of bias assessment of the included studies by two review authors. Results are expressed using risk ratio (RR) for categorical data with 95% confidence intervals (CIs). For outcomes best presented as a rate-per-time-period, rate ratios and standard errors have been used. We performed multiple treatment meta-analyses to rank the effectiveness of each intervention for each outcome. MAIN RESULTS: We included 22 studies involving 7436 participants comparing nine different types of securement device or dressing. All included studies were at unclear or high risk of performance bias due to the different appearances of the dressings and securement devices. The extent of blinding of outcome assessment was unclear in most studies. The quality of evidence varied between different comparisons and outcomes. We mainly downgraded the quality of evidence for imprecision, indirectness, risk of bias and inconsistency.It is unclear whether there is a difference in the rate of catheter-related BSI between securement with gauze and tape and standard polyurethane (SPU) (RR 0.64, 95% CI 0.26 to 1.63, low quality evidence), or between chlorhexidine gluconate-impregnated (CGI) dressings and SPU (RR 0.65, 95% CI 0.40 to 1.05, moderate quality evidence). There is high quality evidence that medication-impregnated dressings reduce the incidence of catheter-related BSI relative to all other dressing types (RR 0.60, 95% CI 0.39 to 0.93).There is moderate quality evidence that CGI dressings reduce the frequency of catheter related BSI per 1000 patient days compared with SPU dressings (RR 0.51, 95% CI 0.33 to 0.78).There is moderate quality evidence that catheter tip colonisation is reduced with CGI dressings compared with SPU dressings (RR 0.58, 95% CI 0.47 to 0.73), but the relative effects of gauze and tape and SPU are unclear (RR 0.95, 95% CI 0.51 to 1.77, very low quality evidence). It is unclear if there is a difference in rates of skin irritation or damage when CGI dressings are compared with SPU dressings (moderate quality evidence) (RR 11.17, 95% CI 0.84 to 149.48).A multiple treatment meta-analysis found sutureless securement devices as likely to be the most effective at reducing the incidence of catheter-related BSI (low quality evidence), with CGI dressings ranked second (low quality evidence). AUTHORS' CONCLUSIONS: Medication-impregnated dressing products reduce the incidence of catheter-related BSI relative to all other dressing types. There is some evidence that CGI dressings, relative to SPU dressings, reduce catheter related BSI for the outcomes of frequency of infection per 1000 patient days, risk of catheter tip colonisation and possibly risk of catheter-related BSI. A multiple treatment meta-analysis found that sutureless securement devices are likely to be the most effective at reducing catheter-related BSI though this is low quality evidence. Most studies were conducted in intensive care unit (ICU) settings. More, high quality research is needed regarding the relative effects of dressing and securement products for CVCs. Future research may adjust the estimates of effect for the products included in this review and is needed to assess the effectiveness of new products. PMID- 26358143 TI - Near-infrared dual-emission quantum dots-gold nanoclusters nanohybrid via co template synthesis for ratiometric fluorescent detection and bioimaging of ascorbic acid in vitro and in vivo. AB - Near-infrared (NIR) quantum dots (QDs) have emerged as an attractive bioimaging toolkit for exploring biological events because they can provide deep imaging penetration and low fluorescence background. However, the quantitation process of such NIR QDs generally relies on single-emission intensity change, which is susceptible to a variety of environmental factors. Herein, for the first time, we proposed a protein-directed co-template strategy to synthesize a NIR-based, dual emission fluorescent nanohybrid (DEFN) constructed from far-red gold nanoclusters and NIR PbS QDs (AuNCs-PbS-QDs). The convenient protein-directed co-template synthesis avoids the tedious chemical coupling and modification required in conventional preparation approaches of DEFNs. Additionally, the dual-emission signals of AuNCs-PbS-QDs exhibit two well-resolved emission peaks (640 and 813 nm) separated by 173 nm, which can eliminate environmental interferences by the built-in correction of ratiometric signal, resulting in a more favorable system for bioimaging and biosensing. Next, the target-responsive capability of this NIR based DEFN to ascorbic acid (AA) was discovered, enabling the proposed DEFN to ratiometrically detect AA with a linear range of 3-40 MUM and a detection limit of 1.5 MUM. This DEFN sensor possesses high selectivity, rapid response, and excellent photostability. Moreover, the feasibility of this NIR nanosensor has been fully proved by the ratiometric detection of AA for fruit internal quality assessment, in vitro cellular imaging, and in vivo imaging in nude mice. PMID- 26358144 TI - An evaluation of dilute acid and ammonia fiber explosion pretreatment for cellulosic ethanol production. AB - The challenge associated with cellulosic ethanol production is maximizing sugar yield at low cost. Current research is being focused to develop a pretreatment method to overcome biomass recalcitrance in an efficient way. This review is focused on two major pretreatments: dilute acid (DA) and ammonia fiber explosion (AFEX) pretreatment of corn stover and how these pretreatment cause morphological and chemical changes to corn stover in order to overcome the biomass recalcitrance. This review highlights the key differences of these two pretreatments based on compositional analysis, cellulose and its crystallinity, morphological changes, structural changes to lignin, enzymatic reactivity and enzyme adsorption onto pretreated solids and finally cellulosic ethanol production from the hydrolysate of DA and AFEX treated corn stover. Each stage of the process, AFEX pretreated corn stover was superior to DA treated corn stover. PMID- 26358145 TI - Total ankle replacement or ankle fusion in painful advanced hemophilic arthropathy of the ankle. AB - In advanced painful hemophilic arthropathy of the ankle, the last resort is surgical treatment (ankle arthrodesis [AA] or total ankle replacement [TAR]). There is a controversy in the literature on which of the two procedures is more appropriate. A review of the literature was performed to clarify such a controversy. The first search engine was MedLine (keywords: total ankle replacement, ankle arthrodesis). Seventy articles were found in MedLine. Of these, only 16 were selected and reviewed because they were strictly focused on the topic of this article. The second search engine was the Cochrane Library, where only nine systematic reviews were found on the role of TAR and AA in non hemophilia patients. TAR and AA provide pain relief and patient satisfaction in hemophilia patients in the short term. The available non-hemophilia literature is insufficient to conclude which treatment is superior. My current view is that AA may be preferable in most hemophilia patients. PMID- 26358146 TI - Predictive validity of endpoints used in electrophysiological modelling of migraine in the trigeminovascular system. AB - The trigeminovascular system has a pivotal role in the pathomechanism of migraine. The aim of the present study was to further develop existing models of migraine making them more suitable for testing the effects of compounds with presumed antimigraine activity in anaesthetised rats. Simultaneous recording of ongoing activity of spontaneously active neurons in the trigeminocervical complex as well as their discharges evoked by electrical stimulation of the dura mater via activation of A- and C-sensory fibres were carried out. Effects of sumatriptan, propranolol and topiramate were evaluated prior to and after application of a mixture containing inflammatory mediators on the dura. Propranolol (10 mg/kg s.c) and topiramate (30 mg/kg s.c.) resulted in a tendency to decrease the level of both spontaneous and evoked activity, while sumatriptan (1 mg/kg s.c.) did not exhibit any effect on recorded parameters. Application of an inflammatory soup to the dura mater boosted up spontaneous activity, which could be significantly attenuated by propranolol and topiramate but not by sumatriptan. In addition, all compounds prevented the delayed increase of spontaneous firing. In contrast to the ongoing activity, evoked responses were not augmented by inflammatory mediators. Nevertheless, inhibitory effect of propranolol and topiramate was evident when considering A- or C-fibre responses. Findings do not support the view that electrically evoked responses are useful for the measurement of trigeminal sensitization. It is proposed however, that inhibition of enhanced firing (immediate and/or delayed) evoked by inflammatory mediators as an endpoint have higher predictive validity regarding the clinical effectiveness of compounds. PMID- 26358147 TI - Development of theta rhythm in hippocampal formation slices perfused with 5-HT1A antagonist, (S)WAY 100135. AB - Numerous studies have revealed that median raphe nuclei stimulation induces desynchronization of hippocampal field activity in vivo. Some findings provide evidence for tonic regulation of the theta oscillation of the septo-hippocampal system via the serotonergic system. To date the involvement of serotonergic transmission in theta rhythm generation in hippocampal slices has never been investigated. Thus the aim of the present study was to test whether HPC in vitro preparation is capable of producing theta in the presence of compounds modulating the activity of 5-HT1A receptors. To achieve this a series of experiments designed to determine the effect of different concentrations of the 5-HT1A receptor antagonist (S)WAY 100135 on HPC field activity was carried out. The dominant field potential pattern recorded within HPC slices was epileptiform activity, with a maximum frequency ranging from 0.19 +/- 0.06 Hz to 0.69 +/- 0.10 Hz. In addition, after the bath application of (S)WAY 100135 in concentrations 3 and 10 uM rhythmic epochs in the theta frequency range were also noted. The highest probability of theta rhythm production was observed after the bath perfusion with a solution of (S) WAY 100135 at a concentration of 10 MUM. These theta rhythm epochs were characterized by a higher-than-average amplitude compared to carbachol-induced theta epochs and shorter time duration, with no apparent differences in the average frequency and duration of intervals between theta epochs. These results obtained herein of in vitro studies provide direct evidence for the involvement of serotonergic receptors in the depression of oscillatory activity in the HPC theta band. PMID- 26358148 TI - Importance of the central nucleus of the amygdala on sodium intake caused by deactivation of lateral parabrachial nucleus. AB - The lateral parabrachial nucleus (LPBN) and the central nucleus of the amygdala (CeA) are important central areas for the control of sodium appetite. In the present study, we investigated the importance of the facilitatory mechanisms of the CeA on NaCl and water intake produced by the deactivation of LPBN inhibitory mechanisms. Male Holtzman rats (n=7-14) with stainless steel cannulas implanted bilaterally in the CeA and LPBN were used. Bilateral injections of moxonidine (alpha2-adrenoceptor/imidazoline agonist, 0.5 nmol/0.2 MUl) into the LPBN increased furosemide+captopril-induced 0.3M NaCl (29.7 +/- 7.2, vs. vehicle: 4.4 +/- 1.6 ml/2h) and water intake (26.4 +/- 6.7, vs. vehicle: 8.2 +/- 1.6 ml/2h). The GABAA agonist muscimol (0.25 nmol/0.2 MUl) injected bilaterally into the CeA abolished the effects of moxonidine into the LPBN on 0.3M NaCl (2.8 +/- 1.6 ml/2h) and water intake (3.3 +/- 2.3 ml/2h). Euhydrated rats treated with muscimol (0.5 nmol/0.2 MUl) into the LPBN also ingested 0.3M NaCl (19.1 +/- 6.4 ml/4h) and water (8.8 +/- 3.2 ml/4h). Muscimol (0.5 nmol/0.2 MUl) into the CeA also abolished 0.3M NaCl (0.1 +/- 0.04 ml/4h) and water intake (0.1 +/- 0.02 ml/4h) in euhydrated treated with muscimol into the LPBN. The present results show that neuronal deactivation of the CeA abolishes NaCl intake produced by the blockade of LPBN inhibitory mechanisms, suggesting an interaction between facilitatory mechanisms of the CeA and inhibitory mechanisms of the LPBN in the control of NaCl intake. PMID- 26358149 TI - Hemispheric specificity for proprioception: Postural control of standing following right or left hemisphere damage during ankle tendon vibration. AB - Right brain damage (RBD) following stroke often causes significant postural instability. In standing (without vision), patients with RBD are more unstable than those with left brain damage (LBD). We hypothesised that this postural instability would relate to the cortical integration of proprioceptive afferents. The aim of this study was to use tendon vibration to investigate whether these changes were specific to the paretic or non-paretic limbs. 14 LBD, 12 RBD patients and 20 healthy subjects were included. Displacement of the Centre of Pressure (CoP) was recorded during quiet standing, then during 3 vibration conditions (80 Hz - 20s): paretic limb, non-paretic limb (left and right limbs for control subjects) and bilateral. Vibration was applied separately to the peroneal and Achilles tendons. Mean antero-posterior position of the CoP, variability and velocity were calculated before (4s), during and after (24s) vibration. For all parameters, the strongest perturbation was during Achilles vibrations. The Achilles non-paretic condition induced a larger backward displacement than the Achilles paretic condition. This condition caused specific behaviour on the velocity: the LBD group was perturbed at the onset of the vibrations, but gradually recovered their stability; the RBD group was significantly perturbed thereafter. After bilateral Achilles vibration, RBD patients required the most time to restore initial posture. The reduction in use of information from the paretic limb may be a central strategy to deal with risk of-fall situations such as during Achilles vibration. The postural behaviour is profoundly altered by lesions of the right hemisphere when proprioception is perturbed. PMID- 26358150 TI - Effects of central gastrin-releasing peptide on glucose metabolism. AB - Gastrin-releasing peptide (GRP) mediated signals in the central nervous system (CNS) influence many functions associated with energy metabolism. The purpose of the present study was to investigate the central effect of GRP on glucose metabolism in the male rat. Intracerebroventricular (icv) administration of GRP caused an immediate hyperglycaemia which was sustained till the end of the infusion. The rise in plasma glucose levels was accompanied by an increase in endogenous glucose production (EGP), as well as increases in plasma glucagon and insulin concentrations. Furthermore, no differences in plasma corticosterone levels were noted between control and GRP treated rats. These results demonstrate that central GRP increases plasma glucose levels, probably by stimulating pancreatic glucagon release and concomitantly or subsequently endogenous glucose production. PMID- 26358151 TI - L-Carnitine inhibits eryptosis induced by uremic serum and the related mechanisms. AB - OBJECTIVE: To investigate whether L-carnitine (LC) inhibits eryptosis induced by uremic serum and the related mechanism. METHODS: One percent erythrocyte suspension was cultured by three kinds of mediums in vitro, which was included in the control group (Group C, phosphate buffered saline [PBS]), the uremic serum group (Group U, 30% uremic serum + 70% PBS) and the LC group (Group L, 30% uremic serum + 70% PBS + 200 umol/L LC), respectively. Erythrocytes were collected at 24 and 48 h, respectively. Phosphatidylserine (PS) was estimated from Annexin-V binding and reactive oxygen species (ROS) by flow cytometry, glutathione (GSH) was estimated from Enzyme linked immunosorbent assays (ELISA) by Microplate reader. RESULTS: Eryptosis in Group C increased as the incubating time extended (3.43 +/- 0.37 at 24 h, 4.21 +/- 0.44 at 48 h). Eryptosis increased in Group U compared with Group C (6.5 1 +/- 0.71 at 24 h, p < 0.01; 8.55 +/- 0.76 at 48 h, p < 0.01), while decreased in Group L compared with Group U (5.80 +/- 0.69 at 24 h, p < 0.05; 7.87 +/- 0.76 at 48 h, p < 0.05). Meanwhile, ROS of erythrocytes increased in Group U compared with Group C (33.12 +/- 1.61 versus 14.83 +/- 2.22 at 24 h, p < 0.01; 42.06 +/- 1.81 versus 20.94 +/- 1.78 at 48 h, p < 0.01), and GSH decreased in Group U compared with Group C (25.66 +/- 0.32 versus 31.27 +/- 0.38 at 24 h, p < 0.01; 8.53 +/- 0.59 versus 17.29 +/- 0.54 at 48 h, p < 0.01). ROS of erythrocytes decreased in Group L compared with Group C (26.29 +/- 1.69 at 24 h, p < 0.01; 36.21 +/- 2.00 at 48 h, p < 0.01). GSH increased in Group L compared with Group U (27.54 +/- 0.60 at 24 h, p < 0.01; 15.18 +/- 0.42 at 48 h, p < 0.01). CONCLUSIONS: LC inhibits eryptosis induced by uremic serum, which possibly relates to oxidative stress in part. PMID- 26358152 TI - Hypertrophic and antihypertrophic microRNA levels in peripheral blood mononuclear cells and their relationship to left ventricular hypertrophy in patients with essential hypertension. AB - MicroRNAs regulate several aspects of physiological and pathologic cardiac hypertrophy, and they represent promising therapeutic targets in cardiovascular disease. We assessed the expression levels of the microRNAs miR-1, miR-133a, miR 26b, miR-208b, miR-499, and miR-21, in 102 patients with essential hypertension and 30 healthy individuals. All patients underwent two-dimensional echocardiography. MicroRNA expression levels in peripheral blood mononuclear cells were quantified by real-time reverse transcription polymerase chain reaction. Hypertensive patients showed significantly lower miR-133a (5.06 +/- 0.50 vs. 13.20 +/- 2.15, P < .001) and miR-26b (6.76 +/- 0.53 vs. 9.36 +/- 1.40, P = .037) and higher miR-1 (25.99 +/- 3.07 vs. 12.28 +/- 2.06, P = .019), miR 208b (22.29 +/- 2.96 vs. 8.73 +/- 1.59, P = .016), miR-499 (10.06 +/- 1.05 vs. 5.70 +/- 0.91, P = .033), and miR-21 (2.75 +/- 0.15 vs. 1.82 +/- 0.20, P = .002) expression levels compared with healthy controls. In hypertensive patients, we observed significant negative correlations of miR-1 (r = -0.374, P < .001) and miR-133a (r = -0.431, P < .001) and significant positive correlations of miR-26b (r = 0.302, P = .002), miR-208b (r = 0.426, P < .001), miR-499 (r = 0.433, P < .001) and miR-21 (r = 0.498, P < .001) expression levels with left ventricular mass index. Our data reveal that miR-1, miR-133a, miR-26b, miR-208b, miR-499, and miR-21 show distinct expression profiles in hypertensive patients relative to healthy individuals and they are associated with clinical indices of left ventricular hypertrophy in hypertensive patients. Thus, they may be related to heart hypertrophy in hypertensive patients and are possibly candidate therapeutic targets in hypertensive heart disease. PMID- 26358153 TI - Corrigendum. AB - In the Foreword by Sandro Barni, titled "Eribulin in 'field practice': an overview of the Italian experience", which appeared in the August 2015 issue of Future Oncology 11(15s), 1-2 (2015), the following sentence was incorrectly presented as: "Casanova et al. [7] in their manuscript comment on the management of a triple-negative patient who maintained eribulin treatment for a total of nine cycles." The correct sentence is: "Casanova et al. [7] in their manuscript comment on the management of a HER2+ patient who maintained eribulin treatment for a total of nine cycles." The authors and editors would like to sincerely apologize for any inconvenience or confusion this may have caused our readers. PMID- 26358155 TI - Calreticulin mutations and their importance in splanchnic vein thrombosis. PMID- 26358154 TI - Novel p53 target genes secreted by the liver are involved in non-cell-autonomous regulation. AB - The tumor-suppressor p53 is a transcription factor that prevents cancer development and is involved in regulation of various physiological processes. This is mediated both by induction of cell cycle arrest and apoptosis and by controlling the expression of a plethora of target genes, including secreted proteins. It has been demonstrated that p53 may exert its effect in non-cell autonomous manner by modulating the expression of genes that encode for secreted factors. In this study, we utilized our microarray data to identify and characterize novel p53 target genes expressed in human liver cells and associated with steroid hormones processing and transfer. We identified the steroid hormones binding factors, sex hormone-binding globulin (SHBG), corticosteroid-binding globulin (CBG) and cytochrome P450 family 21 subfamily A polypeptide 2, as novel p53 target genes. Their expression and secretion was increased following p53 activation in various hepatic cells. We observed that p53 wild-type mice exhibited higher levels of CBG compared with their p53 null counterparts. We demonstrated that the induction of the steroid hormones binding factors can be mediated by binding to specific p53 responsive elements within their promoters. In addition, utilizing conditioned medium experiments we have shown that p53 dependent induction of SHBG secretion from liver cells enhances apoptosis of breast cancer cells. Moreover, depletion of SHBG abolished the induction of breast cancer cells death. The newly identified p53 target genes suggest a novel non-cell-autonomous tumor-suppressive regulation mediated by p53 that is central for maintaining organism homeostasis. PMID- 26358156 TI - The influence of mixed salts on the capacity of HIC adsorbers: A predictive correlation to the surface tension and the aggregation temperature. AB - Hydrophobic interaction chromatography (HIC) is one of the most frequently used purification methods in downstream processing of biopharmaceuticals. During HIC, salts are the governing additives contributing to binding strength, binding capacity, and protein solubility in the liquid phase. A relatively recent approach to increase the dynamic binding capacity (DBC) of HIC adsorbers is the use of salt mixtures. By mixing chaotropic with kosmotropic salts, the DBC can strongly be influenced. For salt mixtures with a higher proportion of chaotropic than kosmotropic salt, higher DBCs were achieved compared with single salt approaches. By measuring the surface tensions of the protein salt solutions, the cavity theory-proposed by Melander and Horvath-that higher surface tensions lead to higher DBCs, was found to be invalid for salt mixtures. Aggregation temperatures of lysozyme in the salt mixtures, as a degree of hydrophobic forces, were correlated to the DBCs. Measuring the aggregation temperatures has proven to be a fast analytical methodology to estimate the hydrophobic interactions and thus can be used as a measure for an increase or decrease in the DBCs. (c) 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:346-354, 2016. PMID- 26358157 TI - Data integrity of the Pediatric Cardiac Critical Care Consortium (PC4) clinical registry. AB - BACKGROUND: Clinical databases in congenital and paediatric cardiac care provide a foundation for quality improvement, research, policy evaluations and public reporting. Structured audits verifying data integrity allow database users to be confident in these endeavours. We report on the initial audit of the Pediatric Cardiac Critical Care Consortium (PC4) clinical registry. Materials and methods Participants reviewed the entire registry to determine key fields for audit, and defined major and minor discrepancies for the audited variables. In-person audits at the eight initial participating centres were conducted during a 12-month period. The data coordinating centre randomly selected intensive care encounters for review at each site. The audit consisted of source data verification and blinded chart abstraction, comparing findings by the auditors with those entered in the database. We also assessed completeness and timeliness of case submission. Quantitative evaluation of completeness, accuracy, and timeliness of case submission is reported. RESULTS: We audited 434 encounters and 29,476 data fields. The aggregate overall accuracy was 99.1%, and the major discrepancy rate was 0.62%. Across hospitals, the overall accuracy ranged from 96.3 to 99.5%, and the major discrepancy rate ranged from 0.3 to 0.9%; seven of the eight hospitals submitted >90% of cases within 1 month of hospital discharge. There was no evidence for selective case omission. CONCLUSIONS: Based on a rigorous audit process, data submitted to the PC4 clinical registry appear complete, accurate, and timely. The collaborative will maintain ongoing efforts to verify the integrity of the data to promote science that advances quality improvement efforts. PMID- 26358158 TI - Exercise therapy for fatigue in multiple sclerosis. AB - BACKGROUND: Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system affecting an estimated 1.3 million people worldwide. It is characterised by a variety of disabling symptoms of which excessive fatigue is the most frequent. Fatigue is often reported as the most invalidating symptom in people with MS. Various mechanisms directly and indirectly related to the disease and physical inactivity have been proposed to contribute to the degree of fatigue. Exercise therapy can induce physiological and psychological changes that may counter these mechanisms and reduce fatigue in MS. OBJECTIVES: To determine the effectiveness and safety of exercise therapy compared to a no-exercise control condition or another intervention on fatigue, measured with self-reported questionnaires, of people with MS. SEARCH METHODS: We searched the Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System Group Trials Specialised Register, which, among other sources, contains trials from: the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 10), MEDLINE (from 1966 to October 2014), EMBASE (from 1974 to October 2014), CINAHL (from 1981 to October 2014), LILACS (from 1982 to October 2014), PEDro (from 1999 to October 2014), and Clinical trials registries (October 2014). Two review authors independently screened the reference lists of identified trials and related reviews. SELECTION CRITERIA: We included randomized controlled trials (RCTs) evaluating the efficacy of exercise therapy compared to no exercise therapy or other interventions for adults with MS that included subjective fatigue as an outcome. In these trials, fatigue should have been measured using questionnaires that primarily assessed fatigue or sub-scales of questionnaires that measured fatigue or sub-scales of questionnaires not primarily designed for the assessment of fatigue but explicitly used as such. DATA COLLECTION AND ANALYSIS: Two review authors independently selected the articles, extracted data, and determined methodological quality of the included trials. Methodological quality was determined by means of the Cochrane 'risk of bias' tool and the PEDro scale. The combined body of evidence was summarised using the GRADE approach. The results were aggregated using meta-analysis for those trials that provided sufficient data to do so. MAIN RESULTS: Forty-five trials, studying 69 exercise interventions, were eligible for this review, including 2250 people with MS. The prescribed exercise interventions were categorised as endurance training (23 interventions), muscle power training (nine interventions), task-oriented training (five interventions), mixed training (15 interventions), or 'other' (e.g. yoga; 17 interventions). Thirty-six included trials (1603 participants) provided sufficient data on the outcome of fatigue for meta-analysis. In general, exercise interventions were studied in mostly participants with the relapsing remitting MS phenotype, and with an Expanded Disability Status Scale less than 6.0. Based on 26 trials that used a non-exercise control, we found a significant effect on fatigue in favour of exercise therapy (standardized mean difference (SMD) -0.53, 95% confidence interval (CI) -0.73 to -0.33; P value < 0.01). However, there was significant heterogeneity between trials (I(2) > 58%). The mean methodological quality, as well as the combined body of evidence, was moderate. When considering the different types of exercise therapy, we found a significant effect on fatigue in favour of exercise therapy compared to no exercise for endurance training (SMDfixed effect -0.43, 95% CI -0.69 to -0.17; P value < 0.01), mixed training (SMDrandom effect -0.73, 95% CI -1.23 to -0.23; P value < 0.01), and 'other' training (SMDfixed effect -0.54, 95% CI -0.79 to 0.29; P value < 0.01). Across all studies, one fall was reported. Given the number of MS relapses reported for the exercise condition (N = 25) and non exercise control condition (N = 26), exercise does not seem to be associated with a significant risk of a MS relapse. However, in general, MS relapses were defined and reported poorly. AUTHORS' CONCLUSIONS: Exercise therapy can be prescribed in people with MS without harm. Exercise therapy, and particularly endurance, mixed, or 'other' training, may reduce self reported fatigue. However, there are still some important methodological issues to overcome. Unfortunately, most trials did not explicitly include people who experienced fatigue, did not target the therapy on fatigue specifically, and did not use a validated measure of fatigue as the primary measurement of outcome. PMID- 26358159 TI - Discovery of (phenoxy-2-hydroxypropyl)piperidines as a novel class of voltage gated sodium channel 1.7 inhibitors. AB - A novel class of NaV1.7 inhibitors has been identified by high-throughput screening followed by structure activity relationship studies. Among this series of compounds, piperidine 9o showed potent human and mouse NaV1.7 inhibitory activities with fair subtype selectivity over NaV1.5. Compound 9o successfully demonstrated analgesic efficacy in mice comparable to that of the currently used drug, mexiletine, but with an expanded central nervous system safety margin. PMID- 26358160 TI - In vivo click reaction between Tc-99m-labeled azadibenzocyclooctyne-MAMA and 2 nitroimidazole-azide for tumor hypoxia targeting. AB - The bioactivity of nitroimidazole in Tc-99m-labeled 2-nitroimidazole, a traditional solid tumor hypoxia-imaging agent for single photon emission computed tomography (SPECT), is reduced by the presence of large ligand and metallic radionuclide, exhibiting lower tumor-to-nontumor ratios. In an effort to solve this general problem, a pretargeting strategy based on click chemistry (strain promoted cyclooctyne-azide cycloaddition) was applied. The functional click synthons were synthesized as pretargeting components: an azide group linked to 2 nitroimidazole (2NIM-Az) serves for tumor hypoxia-targeting and azadibenzocyclooctyne conjugated with monoamine monoamide dithiol ligand (AM) functions as radiolabeling and binding group to azides in vivo. 2NIM-triazole MAMA was obtained from in vitro click reaction with a reaction rate constant of 0.98M(-1)s(-1). AM and 2NIM-triazole-MAMA were radiolabeled with Tc-99m. The hypoxia-pretargeting biodistribution was studied in Kunming mice bearing S180 tumor; (99m)Tc-AM and (99m)Tc-triazole-2NIM were used as blank control and conventional control. Compared to the control groups, the pretargeting experiment exhibits the best radio-uptake and retention in tumor, with higher tumor-to muscle and tumor-to-blood ratios (up to 8.55 and 1.44 at 8h post-(99m)Tc-complex injection, respectively). To some extent, the pretargeting strategy protects the bioactivity of nitroimidazole and therefore provides an innovative approach for the development of tumor hypoxia-SPECT imaging agents. PMID- 26358161 TI - Preface. PMID- 26358162 TI - Neutrophil elastase inhibitors for the treatment of (cardio)pulmonary diseases: Into clinical testing with pre-adaptive pharmacophores. AB - Alpha-1 antitrypsin deficiency is linked with an increased risk of suffering from lung emphysema. This discovery from the 1960s led to the development of the protease-antiprotease (im)balance hypothesis: Overshooting protease concentrations, especially high levels of elastase were deemed to have an destructive effect on lung tissue. Consequently, it was postulated that efficient elastase inhibitors could alleviate the situation in patients. However, despite intensive drug discovery efforts, even five decades later, no neutrophil elastase inhibitors are available for a disease-modifying treatment of (cardio)pulmonary diseases such as chronic obstructive pulmonary disease. Here, we critically review the attempts to develop effective human neutrophil elastase inhibitors while strongly focussing on recent developments. On purpose and with perspective distortion we focus on recent developments. One aim of this review is to classify the known HNE inhibitors into several generations, according to their binding modes. In general, there seem to be three major challenges in the development of suitable elastase inhibitors: (1) assuring sufficient potency, (2) securing selectivity, and (3) achieving metabolic stability especially under pathophysiological conditions. Impressive achievements have been made since 2001 with the identification of potent nonreactive, reversible small molecule inhibitors. The most modern inhibitors bind HNE via an induced fit with a frozen bioactive conformation that leads to a significant boost in potency, selectivity, and stability ('pre-adaptive pharmacophores'). These 5th generation inhibitors might succeed in re-establishing the protease-antiprotease balance in patients for the first time. PMID- 26358163 TI - Reduction of postprandial blood glucose in healthy subjects by buns and flatbreads incorporated with fenugreek seed powder. AB - PURPOSE: This study aimed to determine whether fenugreek seed powder could reduce the glycemic response and glycemic index (GI) when added to buns and flatbreads. METHODS: In a randomised, controlled crossover trial, ten healthy human subjects (five men, five women) were given 50 g glucose (reference food, twice); buns (0 and 10 % fenugreek seed powder); and flatbreads (0 and 10 % fenugreek seed powder) on six different occasions. Finger prick capillary blood samples were collected at 0, 15, 30, 45, 60, 90 and 120 min after the start of the meal. The palatability of the test meals was scored using Likert scales. RESULTS: The incremental areas under the glucose curve value of buns and flatbreads with 10 % fenugreek (138 +/- 17 mmol * min/L; 121 +/- 16 mmol * min/L) were significantly lower than those of 0 % fenugreek bun and flatbreads (227 +/- 15 mmol * min/L; 174 +/- 14 mmol * min/L, P = <0.01). Adding 10 % fenugreek seed powder reduced the GI of buns from 82 +/- 5 to 51 +/- 7 (P < 0.01) and to the GI of flatbread from 63 +/- 4 to 43 +/- 5 (P < 0.01). CONCLUSIONS: These results suggest that replacing 10 % of refined wheat flour with fenugreek seed powder significantly reduces the glycemic response and the GI of buns and flatbreads. Thus, fenugreek powder may be a useful functional ingredient to reduce postprandial glycemia. PMID- 26358164 TI - High-fat diet induces cardiomyocyte apoptosis via the inhibition of autophagy. AB - PURPOSE: Excessive fat intake induces obesity and causes cardiac injury. Intracellular degradation process involving destruction of long-lived proteins and organelles maintains homeostasis for cells under stress. The purpose of this study was to explore the relation of high-fat diet (HFD)-induced cardiac injury and intracellular degradation process with regard to autophagy and ER stress. METHODS AND RESULTS: HFD feeding for 24 weeks induced hyperglycemia, hyperlipidemia, and cardiac hypertrophy in adult male C57BL/6 mice. In the heart, PARP cleavage, an indicator of apoptosis, levels of LC3-II and p62, indicators of autophagy, and CHOP, indicator of ER stress, were increased. A palmitate-treated cardiomyoblast (H9C2) cell culture was examined to explore how HFD induced myocardial injury. Excessive palmitate (400 MUM) treatment induced apoptosis and increased the number of autophagosomes and acid vacuoles of H9C2 cells. Besides, it elevated the expression of LC3-II, p62, and PARP cleavage. Induction of autophagy by rapamycin ameliorated palmitate-induced apoptosis, while inhibition of autophagy by 3-methyladenine or LC3 siRNA exacerbated palmitate-induced apoptosis. Palmitate treatment also induced CHOP expression which is associated with ER stress. CONCLUSION: HFD can cause cardiac injury by induction of apoptosis which is associated with autophagy dysregulation and ER stress. In addition, autophagy deficiency augments cardiac apoptosis, suggesting that autophagy serves as a pro-survival role in lipotoxic condition. PMID- 26358165 TI - The content of docosahexaenoic acid in the maternal diet differentially affects the immune response in lactating dams and suckled offspring. AB - PURPOSE: The objective of this study was to determine the effect of feeding a maternal diet supplemented with docosahexaenoic acid (DHA) while also containing adequate amounts of arachidonic acid on immune system development and function in suckled offspring and lactating rats. METHODS: Sprague-Dawley dams were randomized to one of the two nutritionally adequate experimental diets 24-48 h prior to parturition: control diet (N = 12, 0 % DHA) or high DHA diet (N = 8, 0.9 % DHA of total fatty acids). Diets were fed throughout the lactating/suckling period (21 days), and then, dams and pups were terminated, and immune cell phenotypes and cytokine production by mitogen- or ovalbumin-stimulated splenocytes were measured. RESULTS: Feeding dams a high DHA diet resulted in a higher proportion of 18:3n-3, 22:5n-3 and 22:6n-3 found in pup's stomach content (breast milk; P < 0.01). Feeding the high DHA diet had no impact on growth parameters or the ex vivo cytokine production by mitogen-stimulated splenocytes in both dams and pups. There was a higher proportion of OX12+CD80+ cells and a lower production of TGF-beta by splenocytes after ovalbumin stimulation in pups from dams fed the DHA diet (both P < 0.05) while maintaining a similar IL-2 production. LPS-stimulated splenocytes from dams fed the high DHA diet produced more TNF-alpha versus control diet (P < 0.05). CONCLUSIONS: Overall, our results suggest that DHA supplementation in the maternal diet does not change the immune response to mitogens but positively affects the activation of B cells as well as the response to a potential food antigen upon challenge in suckled offspring. PMID- 26358166 TI - Nut-enriched bread is an effective and acceptable vehicle to improve regular nut consumption. AB - PURPOSE: Consuming 30 g of nuts/day is recommended to reduce chronic disease. However, nut consumption appears far from ideal among several populations. A potential strategy to increase consumption is to add nuts to a staple, for example, bread. Whether the health benefits and acceptability of nuts persist in this form is currently unknown. Thus, we examined the effects of consuming three nut-enriched breads on postprandial glycaemia, satiety, gastrointestinal tolerance, dietary intakes, and acceptance. METHODS: In this controlled, crossover study, 32 participants were randomly allocated to receive one of four breads for 8 days each. Three breads contained either 30 g of finely sliced hazelnuts, 30 g semi-defatted hazelnut flour, or 15 g of each (amounts per 120 g bread) and were compared with a control nut-free bread. Blood glucose response was measured over 120 min, along with ratings of gastrointestinal discomfort. Appetite ratings and diet diaries were completed during each treatment period. RESULTS: Area under the blood glucose curve was significantly lower for the nut breads compared to the control bread (all P < 0.001), with no significant differences between the nut breads (all P >= 0.130). There were no significant differences in satiety (all P >= 0.135) or gastrointestinal symptoms (all P >= 0.102) between the breads. Acceptance was highest for the finely sliced hazelnut bread. Furthermore, consuming hazelnut-enriched bread improved diet quality, increasing monounsaturated fat, vitamin E, and dietary fibre intakes. CONCLUSION: Bread appears to be an effective and acceptable vehicle for increasing nut consumption, resulting in improved postprandial glycaemia and diet profiles. Long term studies are now required. PMID- 26358167 TI - Serogroup A meningococcal conjugate vaccines in Africa. AB - Serogroup A meningococcal epidemics have been a recurrent public health problem, especially in resource-poor countries of Africa. Recently, the administration in mass vaccination campaigns of a single dose of the monovalent meningococcal conjugate vaccine, MenAfriVac, to the 1-29 year-old population of sub-Saharan Africa has prevented epidemics of meningitis caused by serogroup A Neisseria meningitidis. This strategy has also been shown to provide herd protection of the non-vaccinated population. Development of meningococcal conjugate vaccines covering other serogroups and enhanced use of the pneumococcal and Haemophilus influenzae type b conjugate vaccines must be pursued to fully control bacterial meningitis in sub-Saharan Africa. PMID- 26358168 TI - Lipidomics: Novel insight into the biochemical mechanism of lipid metabolism and dysregulation-associated disease. AB - The application of lipidomics, after genomics, proteomics and metabolomics, offered largely opportunities to illuminate the entire spectrum of lipidome based on a quantitative or semi-quantitative level in a biological system. When combined with advances in proteomics and metabolomics high-throughput platforms, lipidomics provided the opportunity for analyzing the unique roles of specific lipids in complex cellular processes. Abnormal lipid metabolism was demonstrated to be greatly implicated in many human lifestyle-related diseases. In this review, we focused on lipidomic applications in brain injury disease, cancer, metabolic disease, cardiovascular disease, respiratory disease and infectious disease to discover disease biomarkers and illustrate biochemical metabolic pathways. We also discussed the analytical techniques, future perspectives and potential problems of lipidomic applications. The application of lipidomics in disease biomarker discovery provides the opportunity for gaining novel insights into biochemical mechanism. PMID- 26358169 TI - NFAT inhibitor tributylhexadecylphosphoniumbromide, ameliorates high fructose induced insulin resistance and nephropathy. AB - High fructose diet (HFrD)-induced insulin resistance (IR) has been reported to be associated with an increase in albuminuria, glomerular hypertrophy and inflammation in kidney. However, the molecular mechanisms associated with high fructose-induced IR and renal dysfunction are still unclear. In the present study, we have investigated the role of nuclear factor of activated T-cell (NFAT) and its inhibitor, Tributylhexadecylphosphoniumbromide (THPB) in high fructose induced IR and renal injury. NFAT inhibition by THPB treatment significantly improved HFrD-induced insulin resistance. Treatment with THPB markedly reduced high fructose diet-induced protein expression of NFATc4, PTEN and also alleviated expression of inflammatory markers in kidneys of HFrD rats. Further, THPB treatment not only improved acute ANG II responses but also repressed the processes of renal fibrosis, ECM accumulation, foot process effacement and renal apoptosis in HFrD rats. Taken together, we for the first time provide evidence that HFrD -induced insulin resistance and renal injury is associated with dysregulated NFATc4/PTEN signalling and THPB prevents this dysregulation through inhibition of NFATc4. Thus, targeting NFATc4 can be a novel therapeutic approach for preventing HFrD induced- IR and renal injury. PMID- 26358170 TI - In vitro exposure of Penicillium mycotoxins with or without a modified yeast cell wall extract (mYCW) on bovine macrophages (BoMacs). AB - Penicillium mycotoxins (PMs) are contaminants that are frequently found in grain or crop-based silage for animal feed. Previously, we have characterized the potential immunotoxicity of the following PMs: citrinin (CIT), ochratoxin A (OTA), patulin (PAT), mycophenolic acid (MPA), and penicillic acid (PA) by using a bovine macrophage cell line (BoMacs). In the present study, cell proliferation was used as a bioassay endpoint to evaluate the efficacy of a modified yeast cell wall extract (mYCW), for preventing PM toxicity under various in vitro conditions such as the following: pH (3, 5, 7), incubation time (1, 2, 4, 6 h), percentage of mYCW (0.05, 0.1, 0.2, 0.5, 1.0 %), and PM concentration. mYCW was most effective in preventing the toxicity of 12.88 and 25.8 MUM OTA at pH 3.0 (p < 0.0001), regardless of incubation time (p < 0.0001) and the percentage of mYCW (p < 0.0001). An incubation time of 6 h (p < 0.05) or 0.5 and 1.0 % mYCW (p < 0.0001) significantly improved the efficacy of mYCW for preventing CIT toxicity. In contrast, 0.5 and 1.0 % of mYCW appeared to exacerbate the PAT toxicity (p < 0. 0001). This effect on PAT toxicity was constantly observed with higher PAT concentrations, and it reached significance at a concentration of 0.70 MUM (p < 0.0001). mYCW had no effect on PA toxicity. These results suggest that mYCW may reduce OTA toxicity and, to some extent, CIT toxicity at pH 3.0. Although PAT toxicity was increased by mYCW treatment, PAT is readily degraded during heat treatment and may therefore be dealt with using other preventative measures. PMID- 26358171 TI - Role of Endothelin-1 in a Syndrome of Myelofibrosis and Osteosclerosis. AB - CONTEXT: Primary myelofibrosis is one of the chronic myeloproliferative disorders characterized by bone marrow fibrosis associated with extramedullary hematopoiesis and osteosclerosis. Endothelin-1 (ET1) is a potent vasoconstrictor that is also a key mediator of osteoblastic bone metastases by stimulating osteoblast proliferation and new bone formation. CASE DESCRIPTION: We report laboratory, radiographic, bone densitometry, and bone histology data of a patient presenting with newly diagnosed, biopsy-proven myelofibrosis and osteosclerosis. We were able to demonstrate abundant ET1 signaling in the bones of our patient. CONCLUSIONS: We believe that ET1 is responsible for the osteosclerosis that develops with advanced myelofibrosis and suggest that ET1 signaling may play a role in other osteosclerotic settings as well. PMID- 26358174 TI - Corrigendum. PMID- 26358172 TI - Bone Density After Teriparatide Discontinuation in Premenopausal Idiopathic Osteoporosis. AB - CONTEXT: Without antiresorptive therapy, postmenopausal women lose bone mass after teriparatide (TPTD) discontinuation; estrogen treatment prevents bone loss in this setting. It is not known whether premenopausal women with regular menses lose bone mass after teriparatide discontinuation. OBJECTIVE: This study aimed to test the hypothesis that normally menstruating premenopausal women with idiopathic osteoporosis (IOP) will maintain teriparatide-associated bone mineral density (BMD) gains after medication cessation. DESIGN: Twenty-one premenopausal IOP women previously enrolled in an open-label pilot study of teriparatide (20 mcg for 18-24 mo), had substantial BMD increases at the lumbar spine (LS; 10.8 +/ 8.3%), total hip (TH; 6.2 +/- 5.6%), and femoral neck (7.6 +/- 3.4%). For this study, BMD was remeasured 2.0 +/- 0.6 years after teriparatide cessation. PARTICIPANTS: Fifteen women, who had gained 11.1 +/- 7.2% at LS and 6.1 +/- 6.5% at TH and were premenopausal at teriparatide completion, were followed without antiresorptive treatment. RESULTS: Two years after completing teriparatide, BMD declined by 4.8 +/- 4.3% (P = .0007) at the LS. In contrast, BMD remained stable at the femoral neck (-1.5 +/- 4.2%) and TH (-1.1 +/- 3.7%). Those who sustained LS bone loss >3% (-7.3 +/- 2.9%; n = 10), did not differ from those with stable LS BMD (0.1 +/- 1.1%; n=5) with regard to baseline body mass index, BMD at any site, or duration of followup, but were significantly older at re-evaluation (46 +/- 3 vs 38 +/- 7; P = .046), had larger increases in LS BMD during teriparatide treatment and higher cancellous bone remodeling on transiliac biopsy at baseline and completion of teriparatide treatment. Serum bone turnover markers did not differ at baseline or teriparatide completion, but tended to be higher at the re evaluation timepoint in those with post-teriparatide bone loss. CONCLUSIONS: These findings lead us to conclude that premenopausal women with IOP, particularly those over 40, may require antiresorptive treatment to prevent bone loss after teriparatide. PMID- 26358173 TI - Testosterone in women--the clinical significance. AB - Testosterone is an essential hormone for women, with physiological actions mediated directly or via aromatisation to oestradiol throughout the body. Despite the crucial role of testosterone and the high circulating concentrations of this hormone relative to oestradiol in women, studies of its action and the effects of testosterone deficiency and replacement in women are scarce. The primary indication for the prescription of testosterone for women is loss of sexual desire, which causes affected women substantial concern. That no formulation has been approved for this purpose has not impeded the widespread use of testosterone by women--either off-label or as compounded therapy. Observational studies indicate that testosterone has favourable cardiovascular effects measured by surrogate outcomes; however, associations between endogenous testosterone and the risk of cardiovascular disease and total mortality, particularly in older women, are yet to be established. Adverse cardiovascular effects have not been seen in studies of transdermal testosterone therapy in women. Clinical trials suggest that exogenous testosterone enhances cognitive performance and improves musculoskeletal health in postmenopausal women. Unmet needs include the availability of approved testosterone formulations for women and studies to elucidate the contribution of testosterone to cardiovascular, cognitive, and musculoskeletal health and the risk of cancer. PMID- 26358175 TI - Olfactory pathway in Xibalbanus tulumensis: remipedian hemiellipsoid body as homologue of hexapod mushroom body. AB - The Remipedia have been proposed to be the crustacean sister group of the Hexapoda. These blind cave animals heavily rely on their chemical sense and are thus rewarding subjects for the analysis of olfactory pathways. The evolution of these pathways as a character for arthropod phylogeny has recently received increasing attention. Here, we investigate the situation in Xibalbanus tulumensis by focal dye injections and immunolabelling of the catalytic subunit of the cAMP dependent protein kinase (DC0), an enzyme particularly enriched in insect mushroom bodies. DC0 labelling of the hemiellipsoid body suggests its subdivision into a cap-like and a core neuropil. Immunofluorescence of the enzyme glutamic acid decarboxylase (GAD), which synthesizes gamma-aminobutyric acid (GABA), has revealed a cluster of GABAergic interneurons in the hemiellipsoid body, reminiscent of the characteristic feedback neurons of the mushroom body. Thus, the hemiellipsoid body of Xibalbanus shares many of the characteristics of insect mushroom bodies. Nevertheless, the general neuroanatomy of the olfactory pathway in the Remipedia strongly corresponds to the malacostracan ground pattern. Given that the Remipedia are probably the sister group of the Hexapoda, the phylogenetic appearance of the typical neuropilar compartments in the insect mushroom body has to be assigned to the origins of the Hexapoda. PMID- 26358177 TI - Early Nonparental Care and Social Behavior in Elementary School: Support for a Social Group Adaptation Hypothesis. AB - This study examined the contribution of nonparental child-care services received during the preschool years to the development of social behavior between kindergarten and the end of elementary school with a birth cohort from Quebec, Canada (N = 1,544). Mothers reported on the use of child-care services, while elementary school teachers rated children's shyness, social withdrawal, prosociality, opposition, and aggression. Children who received nonparental child care services were less shy, less socially withdrawn, more oppositional, and more aggressive at school entry (age 6 years). However, these differences disappeared during elementary school as children who received exclusive parental care caught up with those who received nonparental care services. This "catch-up" effect from the perspective of children's adaptation to the social group is discussed. PMID- 26358178 TI - Structural Insight into Cell Wall Architecture of Micanthus sinensis cv. using Correlative Microscopy Approaches. AB - Structural organization of the plant cell wall is a key parameter for understanding anisotropic plant growth and mechanical behavior. Four imaging platforms were used to investigate the cell wall architecture of Miscanthus sinensis cv. internode tissue. Using transmission electron microscopy with potassium permanganate, we found a great degree of inhomogeneity in the layering structure (4-9 layers) of the sclerenchymatic fiber (Sf). However, the xylem vessel showed a single layer. Atomic force microscopy images revealed that the cellulose microfibrils (Mfs) deposited in the primary wall of the protoxylem vessel (Pxv) were disordered, while the secondary wall was composed of Mfs oriented in parallel in the cross and longitudinal section. Furthermore, Raman spectroscopy images indicated no variation in the Mf orientation of Pxv and the Mfs in Pxv were oriented more perpendicular to the cell axis than that of Sfs. Based on the integrated results, we have proposed an architectural model of Pxv composed of two layers: an outermost primary wall composed of a meshwork of Mfs and inner secondary wall containing parallel Mfs. This proposed model will support future ultrastructural analysis of plant cell walls in heterogeneous tissues, an area of increasing scientific interest particularly for liquid biofuel processing. PMID- 26358176 TI - A 2015 update on predictive molecular pathology and its role in targeted cancer therapy: a review focussing on clinical relevance. AB - In April 2013 our group published a review on predictive molecular pathology in this journal. Although only 2 years have passed many new facts and stimulating developments have happened in diagnostic molecular pathology rendering it worthwhile to present an up-date on this topic. A major technical improvement is certainly given by the introduction of next-generation sequencing (NGS; amplicon, whole exome, whole genome) and its application to formalin-fixed paraffin embedded (FFPE) tissue in routine diagnostics. Based on this 'revolution' the analyses of numerous genetic alterations in parallel has become a routine approach opening the chance to characterize patients' malignant tumors much more deeply without increasing turn-around time and costs. In the near future this will open new strategies to apply 'off-label' targeted therapies, e.g. for rare tumors, otherwise resistant tumors etc. The clinically relevant genetic aberrations described in this review include mutation analyses of RAS (KRAS and NRAS), BRAF and PI3K in colorectal cancer, KIT or PDGFR alpha as well as BRAF, NRAS and KIT in malignant melanoma. Moreover, we present several recent advances in the molecular characterization of malignant lymphoma. Beside the well-known mutations in NSCLC (EGFR, ALK) a number of chromosomal aberrations (KRAS, ROS1, MET) have become relevant. Only very recently has the clinical need for analysis of BRCA1/2 come up and proven as a true challenge for routine diagnostics because of the genes' special structure and hot-spot-free mutational distribution. The genetic alterations are discussed in connection with their increasingly important role in companion diagnostics to apply targeted drugs as efficient as possible. As another aspect of the increasing number of druggable mutations, we discuss the challenges personalized therapies pose for the design of clinical studies to prove optimal efficacy particularly with respect to combination therapies of multiple targeted drugs and conventional chemotherapy. Such combinations would lead to an extremely high complexity that would hardly be manageable by applying conventional study designs for approval, e.g. by the FDA or EMA. Up-coming challenges such as the application of methylation assays and proteomic analyses on FFPE tissue will also be discussed briefly to open the door towards the ultimate goal of reading a patients' tissue as 'deeply' as possible. Although it is yet to be shown, which levels of biological information are most informative for predictive pathology, an integrated molecular characterization of tumors will likely offer the most comprehensive view for individualized therapy approaches. To optimize cancer treatment we need to understand tumor biology in much more detail on morphological, genetic, proteomic as well as epigenetic grounds. Finally, the complex challenges on the level of drug design, molecular diagnostics, and clinical trials make necessary a close collaboration among academic institutions, regulatory authorities and pharmaceutical companies. PMID- 26358179 TI - Tachyphylaxis to local anaesthetics. What is the clinical evidence? A systematic review. AB - BACKGROUND: Tachyphylaxis or acute tolerance to local anaesthetics has been reported, but the prevalence in clinical analgesia is obscure, and the mechanisms behind this phenomenon remain unclear. We sought to examine the clinical significance of tachyphylaxis from the available literature. METHODS: We performed a systematic review of the literature utilising the databases PubMed and Embase employing the search terms [Tachyphylaxis AND Local Anaesthetics AND Human] AND [Tolerance AND Local Anaesthetics AND Human]. RESULTS: A total of 66 records were identified. Thirty-four articles were assessed in full text for eligibility. Twenty studies were considered relevant for qualitative analyses, but only six studies were randomised controlled trials. Because of the heterogeneity of the randomised controlled trials, it was not possible to conduct a meta-analysis. CONCLUSION: Studies documenting tachyphylaxis with clinical use of local anaesthetics are surprisingly scarce, and the mechanisms behind it remain unclear. PMID- 26358180 TI - Preparation of Dental Resins Resistant to Enzymatic and Hydrolytic Degradation in Oral Environments. AB - The short average service life of traditional dental composite restorative materials and increasing occurrence of secondary caries adjacent to composite restorations and sealants are necessitating the development of new, longer lasting compositions. Novel monomers and their polymers, reinforcing fillers, and adhesive components are needed. The goal of this research is to develop resin systems for use in restorations, sealants, and other dental services that are superior in properties and endurance to currently used bisphenol A glycidyl dimethacrylate/triethylene glycol dimethacrylate (Bis-GMA/TEGDMA) and urethane dimethacrylate products. Ether-based monomers and their polymers that were not susceptible to enzymatic or hydrolytic degradation were prepared and characterized. They showed no degradation under hydrolytic and enzymatic challenges, whereas the hydrolysis of ester links weakened contemporary resins within 16 days under these challenges. The success of the ether-based materials is promising in making durable systems that are subjected to long-term biochemical and hydrolytic challenges in oral environments. PMID- 26358181 TI - Breast cancer and immunology: biomarker and therapeutic developments. AB - While breast cancer has not historically been considered an immunogenic cancer, recent data demonstrating the powerful anti-cancer effects of immune checkpoints in many cancers, including breast cancer, has reinvigorated the field. Although the responses are generally low with single agents, some patients experience disease control for a long period of time. Selecting appropriate patients for immunotherapy is an important area of research, and many biomarkers are under investigation. Although immunotherapies are still in their early stages of development, learning how to use them in combination with other agents that can alter antigen presentation or other immune elements will be crucial. This review aims to summarize efforts in immune-related biomarker and drug development, particularly as it pertains to breast cancer. PMID- 26358182 TI - TOPAZ1, a germ cell specific factor, is essential for male meiotic progression. AB - Topaz1 (Testis and Ovary-specific PAZ domain gene 1) is a germ cell specific gene highly conserved in vertebrates. The putative protein TOPAZ1 contains a PAZ domain, specifically found in PIWI, Argonaute and Zwille proteins. Consequently, Topaz1 is supposed to have a role during gametogenesis and may be involved in the piRNA pathway and contribute to silencing of transposable elements and maintenance of genome integrity. Here we report Topaz1 inactivation in mouse. Female fertility was not affected, but male sterility appeared exclusively in homozygous mutants in accordance with the high expression of Topaz1 in male germ cells. Pachytene Topaz1--deficient spermatocytes progress through meiosis without either derepression of retrotransposons or MSCI dysfunction, but become arrested before the post-meiotic round spermatid stage with extensive apoptosis. Consequently, an absence of spermatids and spermatozoa was observed in Topaz1(-/ ) testis. Histological analysis also revealed that disturbances of spermatogenesis take place between post natal days 15 and 20, during the first wave of male meiosis and before the generation of haploid germ cells. Transcriptomic analysis at these two stages showed that TOPAZ1 influences the expression of one hundred transcripts, most of which are up-regulated in mutant testis at post natal day 20. Our results also showed that 10% of these transcripts are long non-coding RNA. This suggests that a highly regulated balance of lncRNAs seems to be essential during spermatogenesis for induction of appropriate male gamete production. PMID- 26358183 TI - Antimicrobial susceptibility and the in vitro postantibiotic effects of vancomycin and ciprofloxacin against Bacillus cereus isolates. AB - BACKGROUND: Vancomycin and ciprofloxacin were often used in the therapy of infections associated with Bacillus cereus. METHODS: Four B. cereus food and clinical isolates were chosen for determination of time-kill curves and postantibiotic effects (PAE) of ciprofloxacin and vancomycin. RESULTS: According to the minimum inhibition concentration (MIC), breakpoints defined by CLSI for Staphylococcus spp. were all four strains intermediate for vancomycin (MIC = 4 MUg/ml) and sensitive to ciprofloxacin (MIC = 0.2 MUg/ml) except the strain Bc63 resistant to the last antimicrobial (MIC = 1.6 MUg/ml). The lowest CFU values of tested strains were reached after 3-5 hours of exposure to 4 * MIC of vancomycin, and after 6-7 hours exposure to 10 * MIC of ciprofloxacin. The maximum reduction of the CFU in the presence of vancomycin and ciprofloxacin was about 2.46 log10 and 2.48 log10, respectively. The average duration of the PAE of vancomycin and ciprofloxacin was 0.94 and 1.60 hours, respectively. The statistically significant differences between PAEs induced with 3 * MIC, 4 * MIC and 8 * MIC of vancomycin were observed (P < 0.05). Both antibiotics did not affect the sporulation of tested bacterial strains. CONCLUSIONS: The differences in PAE duration were strain and antimicrobial dependent. PMID- 26358184 TI - Corrigendum. PMID- 26358186 TI - Cutting in on a secretase pas de deux. AB - Two proteolytic enzymes, beta- and gamma-secretases, work together to produce the amyloid beta-peptide of Alzheimer's disease. New evidence suggests that these proteases directly interact and compounds that disrupt this interaction reduce amyloid beta-peptide levels without directly blocking either enzyme's solo activity. PMID- 26358185 TI - Acute inflammation stimulates a regenerative response in the neonatal mouse heart. AB - Cardiac injury in neonatal 1-day-old mice stimulates a regenerative response characterized by reactive cardiomyocyte proliferation, which is distinguished from the fibrotic repair process in adults. Acute inflammation occurs immediately after heart injury and has generally been believed to exert a negative effect on heart regeneration by promoting scar formation in adults; however, little is known about the role of acute inflammation in the cardiac regenerative response in neonatal mice. Here, we show that acute inflammation induced cardiomyocyte proliferation after apical intramyocardial microinjection of immunogenic zymosan A particles into the neonatal mouse heart. We also found that cardiac injury induced regenerative response was suspended after immunosuppression in neonatal mice, and that cardiomyocytes could not be reactivated to proliferate after neonatal heart injury in the absence of interleukin-6 (IL-6). Furthermore, cardiomyocyte-specific deletion of signal transducer and activator of transcription 3 (STAT3), the major downstream effector of IL-6 signaling, decreased reactive cardiomyocyte proliferation after apical resection. Our results indicate that acute inflammation stimulates the regenerative response in neonatal mouse heart, and suggest that modulation of inflammatory signals might have important implications in cardiac regenerative medicine. PMID- 26358187 TI - mTORC1 maintains metabolic balance. AB - Anticancer therapeutics aimed at the inhibition of mTORC1 activity shift metabolism to favor the degradation of extracellular proteins. Recently Thompson and colleagues demonstrated a novel regulatory mechanism whereby mTORC1 plays a distinct role as a key regulator of metabolism depending on the environmental nutrient status. PMID- 26358188 TI - Pathway mining-based integration of critical enzyme parts for de novo biosynthesis of steviolglycosides sweetener in Escherichia coli. PMID- 26358189 TI - G protein-coupled receptor 183 facilitates endothelial-to-hematopoietic transition via Notch1 inhibition. AB - In vertebrates, embryonic hematopoietic stem and progenitor cells (HSPCs) are derived from a subset of endothelial cells, the hemogenic endothelium (HE), through the endothelial-to-hematopoietic transition (EHT). Notch signaling is essential for HSPC development during embryogenesis across vertebrates. However, whether and how it regulates EHT remains unclear. Here, we show that G protein coupled receptor 183 (Gpr183) signaling serves as an indispensable switch for HSPC emergence by repressing Notch signaling before the onset of EHT. Inhibition of Gpr183 significantly upregulates Notch signaling and abolishes HSPC emergence. Upon activation by its ligand 7alpha-25-OHC, Gpr183 recruits beta-arrestin1 and the E3 ligase Nedd4 to degrade Notch1 in specified HE cells and then facilitates the subsequent EHT. Importantly, 7alpha-25-OHC stimulation promotes HSPC emergence in vivo and in vitro, providing an attractive strategy for enhancing the in vitro generation of functional HSPCs. PMID- 26358190 TI - Siglec1 suppresses antiviral innate immune response by inducing TBK1 degradation via the ubiquitin ligase TRIM27. AB - Type I interferon (IFN) production plays pivotal roles in host antiviral innate immune responses, but an excessive production of type I IFN leads to the development of immunopathological conditions. Investigations on the regulatory mechanisms underlying host type I IFN production are currently of great interest. Here, we found that the expression of lectin family member Siglec1 was upregulated by viral infection in macrophages, which was dependent on the IFN/JAK/STAT1 signaling pathway. Siglec1 was found to negatively regulate viral infection-triggered type I IFN production. Mechanistically, Siglec1 associates with DAP12 to recruit and activate the scaffolding function of SHP2; SHP2 then recruits E3 ubiquitin ligase TRIM27, which induces TBK1 degradation via K48 linked ubiquitination at Lys251 and Lys372. Therefore, viral infection-induced upregulation of Siglec1 feedback loop inhibits type I IFN production and suppresses antiviral innate immune responses. Our study outlines a novel mechanism of negative regulation of type I IFN production, which may help virus to escape immune elimination. PMID- 26358191 TI - Brain region-dependent differential expression of alpha-synuclein. AB - alpha-Synuclein, the major constituent of Lewy bodies (LBs), is normally expressed in presynapses and is involved in synaptic function. Abnormal intracellular aggregation of alpha-synuclein is observed as LBs and Lewy neurites in neurodegenerative disorders, such as Parkinson's disease (PD) or dementia with Lewy bodies. Accumulated evidence suggests that abundant intracellular expression of alpha-synuclein is one of the risk factors for pathological aggregation. Recently, we reported differential expression patterns of alpha-synuclein between excitatory and inhibitory hippocampal neurons. Here we further investigated the precise expression profile in the adult mouse brain with special reference to vulnerable regions along the progression of idiopathic PD. The results show that alpha-synuclein was highly expressed in the neuronal cell bodies of some early PD affected brain regions, such as the olfactory bulb, dorsal motor nucleus of the vagus, and substantia nigra pars compacta. Synaptic expression of alpha-synuclein was mostly accompanied by expression of vesicular glutamate transporter-1, an excitatory presynaptic marker. In contrast, expression of alpha-synuclein in the GABAergic inhibitory synapses was different among brain regions. alpha-Synuclein was clearly expressed in inhibitory synapses in the external plexiform layer of the olfactory bulb, globus pallidus, and substantia nigra pars reticulata, but not in the cerebral cortex, subthalamic nucleus, or thalamus. These results suggest that some neurons in early PD-affected human brain regions express high levels of perikaryal alpha-synuclein, as happens in the mouse brain. Additionally, synaptic profiles expressing alpha-synuclein are different in various brain regions. PMID- 26358193 TI - Altered metabolism of LDL in the arterial wall precedes atherosclerosis regression. AB - RATIONALE: Plasma cholesterol lowering is beneficial in patients with atherosclerosis. However, it is unknown how it affects entry and degradation of low-density lipoprotein (LDL) particles in the lesioned arterial wall. OBJECTIVE: We studied the effect of lipid-lowering therapy on LDL permeability and degradation of LDL particles in atherosclerotic aortas of mice by measuring the accumulation of iodinated LDL particles in the arterial wall. METHODS AND RESULTS: Cholesterol-fed, LDL receptor-deficient mice were treated with either an anti-Apob antisense oligonucleotide or a mismatch control antisense oligonucleotide once a week for 1 or 4 weeks before injection with preparations of iodinated LDL particles. The anti-Apob antisense oligonucleotide reduced plasma cholesterol by ~90%. The aortic LDL permeability and degradation rates of newly entered LDL particles were reduced by ~50% and ~85% already after 1 week of treatment despite an unchanged pool size of aortic iodinated LDL particles. In contrast, the size, foam cell content, and aortic pool size of iodinated LDL particles of aortic atherosclerotic plaques were not reduced until after 4 weeks of treatment with the anti-Apob antisense oligonucleotide. CONCLUSIONS: Improved endothelial barrier function toward the entry of plasma LDL particles and diminished aortic degradation of the newly entered LDL particles precede plaque regression. PMID- 26358192 TI - The Gut Microbiome Contributes to a Substantial Proportion of the Variation in Blood Lipids. AB - RATIONALE: Evidence suggests that the gut microbiome is involved in the development of cardiovascular disease, with the host-microbe interaction regulating immune and metabolic pathways. However, there was no firm evidence for associations between microbiota and metabolic risk factors for cardiovascular disease from large-scale studies in humans. In particular, there was no strong evidence for association between cardiovascular disease and aberrant blood lipid levels. OBJECTIVES: To identify intestinal bacteria taxa, whose proportions correlate with body mass index and lipid levels, and to determine whether lipid variance can be explained by microbiota relative to age, sex, and host genetics. METHODS AND RESULTS: We studied 893 subjects from the Life-Lines-DEEP population cohort. After correcting for age and sex, we identified 34 bacterial taxa associated with body mass index and blood lipids; most are novel associations. Cross-validation analysis revealed that microbiota explain 4.5% of the variance in body mass index, 6% in triglycerides, and 4% in high-density lipoproteins, independent of age, sex, and genetic risk factors. A novel risk model, including the gut microbiome explained <= 25.9% of high-density lipoprotein variance, significantly outperforming the risk model without microbiome. Strikingly, the microbiome had little effect on low-density lipoproteins or total cholesterol. CONCLUSIONS: Our studies suggest that the gut microbiome may play an important role in the variation in body mass index and blood lipid levels, independent of age, sex, and host genetics. Our findings support the potential of therapies altering the gut microbiome to control body mass, triglycerides, and high-density lipoproteins. PMID- 26358194 TI - Association of Neuroprotective Effect of Di-O-Demethylcurcumin on Abeta25-35 Induced Neurotoxicity with Suppression of NF-kappaB and Activation of Nrf2. AB - Amyloid-beta peptides (Abeta), a major component of senile plaques, play an important role in the development and progression of Alzheimer's disease. Several lines of evidence have demonstrated that Abeta-induced neuronal death is mediated by oxidative stress. The present study aimed to evaluate the potential involvement of di-O-demethylcurcumin, an analog of curcuminoid, on Abeta-induced neurotoxicity in culture neuroblastoma cells (SK-N-SH cells) through the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway and the suppression of nuclear factor-kappaB (NF-kappaB) signaling pathway and their downstream targets. The results showed that pretreatment with di-O-demethylcurcumin elevated cell viability and decreased the level of reactive oxygen species. Moreover, treatment with di-O-demethylcurcumin promoted the translocation of Nrf2 protein from the cytoplasm to the nucleus, increased the expression of Nrf2-ARE pathway-related downstream proteins including heme oxygenase (HO-1), NAD(P)H:quinone oxidoreductase 1 and glutamate-cysteine ligase catalytic subunit, and increased the activity of superoxide dismutase enzymes. On the other hand, di-O-demethylcurcumin suppressed the degradation of IkappaBalpha, translocation of the p65 subunit of NF-kappaB from cytoplasm to nucleus and thereby, attenuated the expression of inducible nitric oxide synthase protein and nitric oxide production. Taken together, these results suggest that neuroinflammatory effect of di-O-demethylcurcumin might potentially be due to inhibit NF-kappaB and activate Nrf2 signaling pathways induced by Abeta25-35. PMID- 26358195 TI - Trophic versus structural effects of a marine foundation species, giant kelp (Macrocystis pyrifera). AB - Foundation species create milieus in which ecosystems evolve, altering species abundances and distribution often to a dramatic degree. Although much descriptive work supports their importance, there remains little definitive information on the mechanisms by which foundation species alter their environment. These mechanisms fall into two basic categories: provision of food or other materials, and modification of the physical environment. Here, we manipulated the abundance of a marine foundation species, the giant kelp Macrocystis pyrifera, in 40 * 40-m plots at Mohawk Reef off Santa Barbara, California and found that its biomass had a strong positive effect on the abundance of bottom-dwelling sessile invertebrates. We examined the carbon (C) stable isotope values of seven species of sessile invertebrates in the treatment plots to test the hypothesis that this positive effect resulted from a nutritional supplement of small suspended particles of kelp detritus, as many studies have posited. We found no evidence from stable isotope analyses to support the hypothesis that kelp detritus is an important food source for sessile suspension-feeding invertebrates. The isotope composition of invertebrates varied with species and season, but was not affected by kelp biomass, with the exception of two species: the tunicate Styela montereyensis, which exhibited a slight enrichment in C stable isotope composition with increasing kelp biomass, and the hydroid Aglaophenia sp., which showed the opposite effect. These results suggest that modification of the physical habitat, rather than nutritional subsidy by kelp detritus, likely accounts for increased abundance of sessile invertebrates within giant kelp forests. PMID- 26358196 TI - Three-Dimensional Microstructure Reconstruction and Finite Element Simulation of Gas Pores in the High-Pressure Die-Casting AZ91 Mg Alloy. AB - High-pressure die-casting (HPDC) AZ91 tensile specimens were used to investigate characteristics of gas pores and their effects on mechanical properties of HPDC AZ91 magnesium (Mg) alloy. Combining the stereoscopic morphology of gas pores obtained from a three-dimensional (3D) reconstruction technique with the experimental data from uniaxial tensile testing, we worked on finite element simulation to find the relationship between gas pores and the mechanical properties of HPDC AZ91 Mg alloy. Results indicate that the 2D metallography images have one-sidedness. Moreover, gas pores >100 um in the center region have a remarkable negative influence on the ultimate tensile strength (UTS) and elongation. With an increase in the size of large gas pores in the center region, the UTS and elongation of the material decreases. In addition, the distribution of gas pores in the specimens and the areal fraction of gas pores >100 um on cross sections can also affect the UTS and elongation to some extent. PMID- 26358197 TI - Prognostic factors for glioblastoma patients--a clinical population-based study. AB - OBJECTIVES: To address in a retrospective and population-based study prognostic factors for survival time after diagnosis and surgery for glioblastoma multiforme (GBM). MATERIAL AND METHODS: During the study period, 430 patients were identified at the multidisciplinary team conferences as newly diagnosed GBM, 201 of these were considered not to benefit from surgery, and thus, a total of 229 consecutive adult patients with GBM were operated between January 2004 and December 2008 at Sahlgrenska University Hospital and were retrospectively analyzed. Potential predictors of survival were statistically analyzed using Poisson regression models. RESULTS: Median survival was 0.73 years. Multivariable analysis showed the following factors to positively influence survival: younger age at surgery, secondary tumor genesis, unifocal tumor location (vs multifocal), resection (vs biopsy only), radiotherapy, and combination of radiotherapy and chemotherapy. CONCLUSION: This population-based study supports the importance of surgery instead of biopsy only, followed by radiotherapy and chemotherapy, a finding which has also been stated in earlier non-population-based reports. However, it is obvious that the solution is not just surgical radicality followed by optimal oncological treatment. It is of great importance to seek further subclassifications, biomarkers, and new treatment modalities to make a significant change in survival for individuals. PMID- 26358198 TI - Oil Recovery from Water under Environmentally Relevant Conditions Using Magnetic Nanoparticles. AB - Large oil spills and oily wastewater discharges from ships and industrial activities can have serious impacts on the environment with potentially major economic impacts. Current oil remediation techniques are inefficient and may have deleterious environmental consequences. However, nanotechnology offers a new route to potentially remediate oil pollution. In this study, a cheap and facile hydrothermal method was developed to synthesize polyvinylpyrrolidone-coated magnetite nanoparticles to separate a reference MC252 oil from oil-water mixture under environmentally relevant conditions. Fluorescence and Proton nuclear magnetic resonance spectroscopy results showed near 100% oil removal from oil water mixture in the ultrapure water under optimum condition. Based on gas chromatography-mass spectrometry data, approximately 100% of lower molecular mass alkanes (C9-C21) were removed within 10 min of magnetic separation and by increasing the separation time to 40 min, greater than 67% of C22-25 alkanes were removed. Moreover, nanoparticles removed near 100% oil from synthetic seawater solutions in the presence and absence of fulvic acid showing excellent oil removal capacity of the nanoparticles under different conditions. Results show that these nanoparticles can be utilized to remove oil over a short time with a high removal efficiency under environmentally relevant conditions. PMID- 26358199 TI - Outcomes of extended transforaminal lumbar interbody fusion for lumbar spondylosis. AB - This study aims to assess the results of extended transforaminal lumbar interbody fusion (TLIF) for a two surgeon, single institution series. In total, extended TLIF with bilateral decompression was performed in 57 patients. Pain, American Spinal Injury Association scores, patient demographics, body mass index (BMI), perioperative indices and radiographic measurements were recorded and analysed. The surgeries were performed between February 2011 and January 2014 on 38 women and 19 men. The mean patient age was 62.86 years, and the mean BMI was 30.31 kg/m(2). In 49 patients, spondylolisthesis was the primary indication. The mean intraoperative time was 284.65 min, and this decreased as the series progressed. The median length of stay was 5 days (range: 2-9). The surgical complication rate was 19.3%. Two patients died from cardiopulmonary complications. Single level TLIF was performed in 78.9% of the cohort, with L4/5 the most commonly fused level. Significant pain reduction was achieved from a mean (+/- standard deviation) preoperative visual analogue scale (VAS) of 8.28 +/- 1.39 to 1.50 +/- 1.05 at 12 months postoperatively. No patients deteriorated neurologically. Spondylolisthesis was significantly corrected from a preoperative mean of 6.82 mm to 2.80 mm postoperatively. Although there is a learning curve associated with the procedure, extended TLIF with bilateral facet joint removal and decompression appeared to be a safe and effective alternative to other fusion techniques, and our results were comparable to other published case series. The stabilisation and correction of spinal deformity reduces pain, aids neurologic recovery and improves quality of life. PMID- 26358200 TI - Incidence and risk of delayed surgical site infection following instrumented lumbar spine fusion. AB - We reviewed a retrospective case series of patients with delayed infections after spinal fusion, and surveyed medical experts in Canada and the USA regarding their use of prophylactic antibiotics for patients undergoing invasive procedures following spine surgery. Infections after spinal fusion are a relatively common complication, which typically occur early in the postoperative period. Infections which occur more than 3months from the index procedure are rare and are often caused by atypical pathogens. The proportion of infections that required debridement and occurred 6 months after the index procedure was 4.3% (7/162). Over 85% of these infections were polymicrobial, with one third of those containing methicillin-resistant Staphylococcus aureus. The most common operative indications were either trauma or tumour, and most patients with a delayed infection had a distant chronic infection. The majority of spine experts do not routinely recommend prophylactic antibiotics for invasive procedures after spine fusion. In the multivariate analysis, experts were more likely to recommend antibiotics for patients undergoing a non-dental procedure, those who were diabetic, and those who were greater than 1year out from their procedure. In summary, the delayed presentation of infection after instrumented spinal fusion is a rare but serious complication. However, due to its infrequency, routine prophylaxis to prevent haematogenous seeding is likely unnecessary. PMID- 26358201 TI - Giant, calcified colloid cyst of the lateral ventricle. AB - We report a patient with a giant, calcified colloid cyst in the left lateral ventricle. Colloid cysts are slow growing, benign lesions, commonly originating in the roof of the anterior third ventricle near the foramen of Monro. Many colloid cysts are small lesions which are either discovered incidentally or cause headache, visual changes, memory deficits, and/or syncope. Giant colloid cysts are rare. A 40-year-old man presented with a month long history of worsening headaches and was found to have a multiloculated 5 cm intraventricular mass with an anterior hyperdensity, suggestive of calcification, arising within the lateral ventricles. He underwent an interhemispheric transcallosal approach for resection of the mass. The pathology was consistent with a giant colloid cyst with calcification in the anterior cyst wall. Giant, calcified mass is a rare presentation of colloid cyst. Although rare, this diagnosis remains an important consideration in the differential diagnosis of any calcified, cystic intraventricular mass. PMID- 26358202 TI - Impact of GLP-1 receptor agonists on blood pressure, heart rate and hypertension among patients with type 2 diabetes: A systematic review and network meta analysis. AB - AIMS: To evaluate current evidence of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on blood pressure, heart rate, and hypertension in patients with type 2 diabetes. METHODS: Medline, Embase, the Cochrane library, and the website www.clinicaltrials.gov were searched on April 5th, 2014. Randomized-controlled trials with available data were included if they compared GLP-1RAs with placebo and traditional antidiabetic drugs in patients with type 2 diabetes with duration >= 12 weeks. Weighted mean difference for blood pressure and heart rate, odds ratio (OR) for hypertension were calculated by random-effect model. Network meta analysis was performed to supplement direct comparisons. RESULTS: Sixty trials with 14 treatments were included. Compared with placebo, insulin, and sulfonylureas, GLP-1RAs decreased systolic blood pressure with range from -1.84 mmHg (95% CI: -3.48 to -0.20) to -4.60 mmHg (95% CI: -7.18 to -2.03). Compared with placebo, a reduction in diastolic blood pressure was detected significantly only for exenatide-10 MUg-twice-daily (-1.08 mmHg, 95% CI: -1.78 to -0.33). Exenatide (2 mg once weekly), liraglutide 1.2 mg once daily), and liraglutide (1.8 mg once daily) increased heart rate by 3.35 (95% CI: 1.23-5.50), 2.06 (95% CI: 0.43, 3.74), and 2.35 (95% CI: 0.94-3.76) beats/min versus placebo. This effect was evident compared with active control (range: 2.22-3.62). No significant association between incident hypertension and GLP-1RAs was detected, except for the association between exenatide-10 MUg-twice-daily and sulfonylureas (OR, 0.40, 95% CI: 0.16, 0.82). CONCLUSIONS: GLP-1RAs were associated with modest reduction on blood pressure, a slight increase in heart rate, yet no significant association with hypertension. Further investigation to explore mechanisms is warranted. PMID- 26358203 TI - Prescribing patterns for upper respiratory tract infections: a prescription review of primary care practice in Kedah, Malaysia, and the implications. AB - INTRODUCTION AND AIMS: It is necessary to ascertain current prescribing of antibiotics for upper respiratory tract infections (URTIs) to address potential overuse. A retrospective analysis was conducted of all prescriptions for URTIs among 10 public primary healthcare centers in Kedah, Malaysia, from 1 January to 31 March 2014. RESULTS: A total of 123,524 prescriptions were screened and analyzed. Of these, 7129 prescriptions were for URTI, with 31.8% (n = 2269) containing antibiotics. Macrolides were the most commonly prescribed antibiotic, constituting 61% (n = 1403) of total antibiotics prescribed. There was a statistically significant association between different prescribers and diagnoses (p = 0.001) and a weak positive trend suggesting family medicine specialists are more competent in antibiotic prescribing, followed by medical officers and assistant medical officers (tau = 0.122). CONCLUSIONS: Prescribing practices of some prescribers were inconsistent with current guidelines encouraging resistance development. National antimicrobial stewardship programs and further educational initiatives are ongoing in Malaysia to improve antibiotic use. PMID- 26358204 TI - Future therapeutic targets for the treatment and prevention of cholesterol gallstones. AB - The formation of cholesterol gallstones involves very complex imbalances, such as alterations in the secretion of biliary lipids (which involves the ABCG5, ABCG8, ABCB4 and ABCB11 transporters), biochemical and immunological reactions in the gallbladder that produce biliary sludge (mucins), physicochemical changes in the structure of cholesterol (crystallization), alterations in gallbladder motility, changes in the intestinal absorption of cholesterol (ABCG5/8 transporters and Niemann-Pick C1L1 protein) and alterations in small intestine motility. Some of these proteins have been studied at the clinical and experimental levels, but more research is required. In this review, we discuss the results of studies on some molecules involved in the pathophysiology of gallstones that may be future therapeutic targets to prevent the development of this disease, and possible sites for treatment based mainly on the absorption of intestinal cholesterol (Niemann-Pick C1L1 and ABCG5/8 proteins). PMID- 26358205 TI - Statin-mediated inhibition of cholesterol synthesis induces cytoprotective autophagy in human leukemic cells. AB - Statins exhibit anti-leukemic properties due to suppression of the mevalonate pathway by the inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase, and subsequent depletion of cholesterol, farnesylpyrophosphate, and geranylgeranylpyrophosphate. We investigated the role of autophagy, a controlled intracellular self-digestion, in the anti-leukemic action of statins. Treatment with low concentrations (<=6 uM) of statins, cholesterol depletion, and specific inhibition of cholesterol synthesis and protein farnesylation or geranylgeranylation, all inhibited proliferation of leukemic cell lines and primary leukemic cells without inducing overt cell death. Statins and agents that selectively reduce intracellular cholesterol levels, but not the inhibition of protein farnesylation or geranylgeranylation, induced autophagy in leukemic cells. The observed autophagic response was associated with the reduction of phosphorylated Akt levels in the lipid rafts, accompanied by a decrease in the activation of the main autophagy suppressor mammalian target of rapamycin (mTOR) and its substrate ribosomal p70S6 kinase (p70S6K). No significant autophagy induction and downregulation of mTOR/p70S6K activation were observed in normal leukocytes. Autophagy suppression by bafilomycin A1 or RNA interference-mediated knockdown of beclin-1 and microtubule-associated protein 1 light chain 3B induced apoptotic death in statin-treated leukemic cells, an effect attenuated by the addition of mevalonate or squalene, but not farnesylpyrophosphate or geranylgeranylpyrophosphate. Therefore, while the inhibition of cholesterol synthesis, protein farnesylation, and geranylgeranylation all contributed to anti leukemic effects of statins, the inhibition of cholesterol synthesis was solely responsible for the induction of cytoprotective autophagy. These data indicate that combined treatment with statins and autophagy inhibitors might be potentially useful in anti-leukemic therapy. PMID- 26358206 TI - Influence of nitrogen form on the phytoextraction of cadmium by a newly discovered hyperaccumulator Carpobrotus rossii. AB - Using hyperaccumulator plants is an important method to remove heavy metals from contaminated land. Carpobrotus rossii, a newly found Cd hyperaccumulator, has shown potential to remediate Cd-contaminated soils. This study examined the effect of nitrogen forms on Cd phytoextraction by C. rossii. The plants were grown for 78 days in an acid soil spiked with 20 mg Cd kg(-1) and supplied with (NH4)2SO4, Ca(NO3)2, urea, and chicken manure as nitrogen (N) fertilizers. Nitrification inhibitor dicyandiamide (DCD) was applied to maintain the ammonium (NH4(+)) form. Nitrogen fertilization increased shoot biomass but decreased root biomass with the highest shoot biomass occurring in the manure treatment. Compared to the no-N control, urea application did not affect shoot Cd concentration, but increased Cd content by 17% due to shoot biomass increase. Chicken manure significantly decreased CaCl2-extractable Cd in soil, and the Cd concentration and total Cd uptake in the plant. Rhizosphere pH was the highest in the manure treatment and the lowest in the NH4(+) treatments. The manure and nitrate (NO3(-)) treatments tended to have higher rhizosphere pH than their respective bulk soil pH, whereas the opposite was observed for urea and NH4(+) treatments. Furthermore, the concentrations of extractable Cd in soil and Cd in the plant correlated negatively with rhizosphere pH. The study concludes that urea significantly enhanced the Cd phytoaccumulation by C. rossii while chicken manure decreased Cd availability in soil and thus the phytoextraction efficiency. PMID- 26358207 TI - Role of xylo-oligosaccharides in protection against salinity-induced adversities in Chinese cabbage. AB - Soil salinity is a stringent abiotic constraint limiting crop growth and productivity. The present study was carried out to appraise the role of xylo oligosaccharides (XOSs) in improving the salinity tolerance of Chinese cabbage. Salinity stress (0.5% NaCl solution) and four levels (0, 40, 80, 120 mg L(-1)) of XOSs were imposed on 20-day-old plants cultured under controlled conditions. Salinity stress decreased the aboveground fresh biomass, photosynthesis, transpiration rate, stomatal conductance, internal CO2 concentration, water use efficiency, and chlorophyll contents but increased the stomatal limitation value of Chinese cabbage compared with control. Such physiological interferences, disturbances in plant water relations, and visually noticeable growth reductions in Chinese cabbage were significantly alleviated by the addition of XOSs under salinity stress. Under salinity stress, application of XOSs significantly enhanced the activities of enzymatic (superoxide dismutase, peroxidase, catalase) and non-enzymatic (ascorbate, carotene) antioxidants and reduced the malondialdehyde content in the leaves of Chinese cabbage. The XOS-applied plants under salinity stress also recorded higher soluble sugars, proline, and soluble protein content in their leaves. Exposure of salinity stress increased the ratio of Na(+)/K(+), Na(+)/Ca(2+), and Na(+)/Mg(2+) in shoot as well as root of Chinese cabbage, however, XOS application significantly reduced these ratios particularly in shoot. Lower levels of XOSs (40 or 80 mg L(-1)) were more effective for most of the studied attributes. The greater salinity tolerance and better growth in these treatments were related with enhanced antioxidative defense system, reduced lipid peroxidation, increased osmolyte accumulation, and maintenance of ionic balance. PMID- 26358208 TI - Subacute static magnetic field exposure in rat induces a pseudoanemia status with increase in MCT4 and Glut4 proteins in glycolytic muscle. AB - The purpose of this study was to investigate the effect of subacute exposure to static magnetic fields (SMF) on hematological and muscle biochemical parameters in rats. Male Wistar rats, daily exposed to SMF, were exposed to SMF (128 mT, 1 h/day) during 15 consecutive days. SMF-exposed rats showed a significant decrease in red blood cell (RBC) count, hemoglobin (Hb), and hematocrit (Ht) values compared to sham-exposed rats (p < 0.05). Concomitant decreases of plasma iron level against increase in transferrin amount were also observed after SMF exposure (p < 0.0.05). In postprandial condition, SMF-exposed rats presented higher plasma lactate (p < 0.01). Additionally, SMF exposure increased monocarboxylate transporters (MCT4) and glucose transporter 4 (Glut4)'s contents only in glycolytic muscle (p < 0.05). SMF exposure induced alteration of hematological parameters; importantly, we noticed a pseudoanemia status, which seems to affect tissue oxygen delivery. Additionally, SMF exposure seems to favor the extrusion of lactate from the cell to the blood compartment. Given that, these arguments advocate for an adaptive response to a hypoxia status following SMF exposure. PMID- 26358209 TI - Application of the GREAT-ER model for environmental risk assessment of nonylphenol and nonylphenol ethoxylates in China. AB - The environmental risk presented by "down-the-drain" chemicals to receiving rivers in large urban areas has received increasing attention in recent years. Geo-referenced Regional Environmental Assessment Tool for European Rivers (GREAT ER) is a typical river catchment model that has been specifically developed for the risk assessment of these chemicals and applied in many European rivers. By utilizing the new version of the model, GREAT-ER 3.0, which is the first completely open source software for worldwide application, this study represents the first attempt to conduct an application of GREAT-ER in the Wenyu River of China. Aquatic exposure simulation and an environmental risk assessment of nonylphenol (NP) and its environmental precursor nonylphenol ethoxylates (NPEOs) were conducted effectively by GREAT-ER model, since NP is one of typical endocrine disrupting chemicals (EDCs) and its environmental precursor NPEOs as a "down-the-drain" chemical are extensively used in China. In the result, the predicted environmental concentrations (PECs) of NP and NPEOs in the water of Wenyu River were 538 and 4320 ng/L, respectively, at the regional scale, and 1210 and 8990 ng/L, respectively, at the local scale. From the results profile of the RCR, the combination of high emissions from large STPs with insufficient dilution of the river caused the high RCR. The PECs of NP in the sediment were in the range of 216.8-8218.3 ng/g (dry weight), which was consistent with the available monitoring data. The study showed the worldwide applicability and reliability of GREAT-ER as a river catchment model for the risk assessment of these chemicals and also revealed the general environmental risks presented by NP and NPEOs in the Wenyu River catchment in Beijing due to the extensive use of these chemicals. The results suggest that specific control or treatment measures are probably warranted for these chemicals to reduce their discharge in major cities. PMID- 26358210 TI - Healing the wounds in the landscape-reclaiming gravel roads in conservation areas. AB - Reclaiming abandoned and unmaintained roads, built originally for forestry and mineral extraction, is an important part of ecological restoration, because the roads running through natural habitats cause fragmentation. The roads can be reclaimed in a passive way by blocking access to the road, but successful seedling recruitment may require additional management due to the physical constraints present at the road. We established a full factorial study to compare the effects of three road reclaiming measures, namely ripping, creation of safe sites by adding mulch and pine seed addition, on soil processes, recovery of understorey vegetation and seedling recruitment in three conservation areas in eastern Finland. We surveyed soil organic matter, frequency and cover of plant functional types, litter and mineral soil, and number of tree seedlings. The soil organic matter was, on average, 1.3-fold in the 50-cm-deep ripping treatment relative to unripped and 20-cm-deep ripping treatments. The germination and survival of deciduous seedlings and grass establishment were promoted by adding mulch. The addition of pine seeds counteracted the seed limitation and enhanced the regeneration of trees. The treatment combination consisting of ripping, adding mulch and pine seed addition enhanced the vegetation succession and tree seedling recruitment most: the cover of grasses, herbs and ericaceous dwarf shrubs was 1.3-7.6-fold and the number of coniferous tree seedlings was 3.4-7.1 fold relative to the other treatment combinations. Differences between short-term (1-3 years) and longer-term (6 years) results indicate the need for a sufficient observation period in road reclamation studies. PMID- 26358211 TI - Thermal mineralization behavior of PFOA, PFHxA, and PFOS during reactivation of granular activated carbon (GAC) in nitrogen atmosphere. AB - Waste disposal site is one of the important sinks of chemicals. A significant amount of perfluoroalkyl and polyfluoroalkyl substances (PFASs) such as perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), and perfluorohexanoic acid (PFHxA) have been brought into it. Because of their aqueous solubility, PFASs are released to landfill effluent waters, from which PFASs are efficiently collected by adsorption technique using granular activated carbon (GAC). The exhausted GAC is reactivated by heating processes. The mineralization of PFASs during the reactivation process was studied. Being thermally treated in N2 atmosphere, the recovery rate of mineralized fluorine and PFC homologues including short-chained perfluorocarboxylic acids was determined. If the reagent form of PFOA, PFHxA, and PFOS were treated at 700 degrees C, the recovery of mineralized fluorine was less than 30, 46, and 72 %, respectively. The rate increased to 51, 74, and 70 %, if PFASs were adsorbed onto GAC in advance; moreover, addition of excess sodium hydroxide (NaOH) improved the recovery to 74, 91, and 90 %. Residual PFAS homologue was less than 1 % of the original amount. Steamed condition did not affect destruction. The significant role of GAC was to suppress volatile release of PFASs from thermal ambient, whereas NaOH enhanced destruction and retained mineralized fluorine on the GAC surface. Comparing the recovery of mineralized fluorine, the degradability of PFOS was considered to be higher than PFOA and PFHxA. Whole mass balance missing 9~26 % of initial amount suggested formation of some volatile organofluoro compounds beyond analytical coverage. PMID- 26358212 TI - Tracking the monthly changes of dissolved organic matter composition in a newly constructed reservoir and its tributaries during the initial impounding period. AB - Understanding the roles of inland reservoirs becomes increasingly important with respect to global carbon cycling as well as water resource management due to the unprecedented demand for construction in recent decades. In this study, the dissolved organic matter (DOM) quantity and quality in a newly constructed dam reservoir and its tributaries were monitored monthly during the initial impounding period (July to November 2014) using a size exclusion chromatography (SEC) with online organic carbon detector (OCD). The highest values were observed in the month of August with the highest precipitation for the bulk dissolved organic carbon (DOC), specific UV absorbance (SUVA), and most of the assigned size fractions (except for biopolymers) in the tributaries, indicating that allochthonous sources of DOM were dominant in the feeding stream waters of the reservoir. The bulk DOC and high molecular weight humic substance fraction (~1 kDa) were generally co-varied with the monthly precipitation in the tributaries, while building blocks (350-500 Da), and low molecular weight (LMW) acids and neutrals showed different trends. In a dam site, the smaller molecular fractions became more abundant during the dry season (September to November), presumably due to the in-reservoir processes such as photo- and bio-degradation. Our results also revealed that storms mobilized a large amount of highly aromatic soil derived DOM to the reservoir. A depth profile at the dam site showed the water is well mixed up to a depth of ~20 m. The SEC-OCD data coupled with non-metric multidimensional scaling provided a clear visualization of the spatiotemporal variations in DOM composition, which shed new light on the DOM composition formed in a newly constructed dam reservoir and also on the strategies for future water treatment options. PMID- 26358214 TI - The impact of mariculture on nutrient dynamics and identification of the nitrate sources in coastal waters. AB - Reclamation along coastal zones is a method that has been used to relieve the problems of strained resources and land. Aquaculture, as one of the major man made activities in reclamation areas, has an environmental impact on coastal waters. The effluents from aquaculture ponds are known to enrich the levels of nutrients such as nitrogen and phosphate. The goals of the present study are to evaluate the environmental impact of mariculture on coastal waters in the east coast of Laizhou Bay, China, and to identify the nitrate sources. Monitoring the concentrations of dissolved nitrogen and phosphate was used to assess their impact on the water quality of coastal waters. A dual isotope (delta(15)N-NO3(-) and delta(18)O-NO3(-)) approach was used to identify the nitrate sources. Higher dissolved nitrogen concentrations (NH4(+) and NO3(-)) than PO4(3-) concentrations associated with enriched delta(15)N-NO3(-) values were observed in the drainage channels, sea cucumber ponds, and groundwater, which indicated that aquaculture activity has more influence on nitrogen nutrients than on phosphate nutrients. In this coastal area with seawater intrusion, nitrogen released from sea cucumber ponds accumulated in nearshore water and migrated in the offshore direction in groundwater currents. This behavior results in nitrogen enrichment in groundwater within the hinterland. Isotopic data indicate that mixing of multiple nitrate sources exists in groundwater, and nitrogen from mariculture is the main source. PMID- 26358213 TI - Biomarkers of PAH exposure and hematologic effects in subjects exposed to combustion emission during residential (and professional) cooking practices in Pakistan. AB - The aim of this study was to evaluate and compare the exposure of household women and professional male workers to combustion emission in the indoor and semi outdoor environments, respectively, by using biochemical parameters and the biomarkers of exposure to polycyclic aromatic hydrocarbon (PAH). Female (WR n = 60) and male "cooks" (WC n = 60) exposed to the combustion emission of fuel wood and coal in rural/suburban areas of Pakistan were recruited in this study and compared to non-exposed female (CF) and male (CM) groups (n = 32 and 34, respectively). Urinary biomarkers of PAH exposure including 1-hyroxypyrene (1 OHPyr), alpha-naphthol, and beta-naphthol were analyzed together with the biomarkers of effect, including the serum c-reactive proteins (CRP), white blood cells (WBCs), hemoglobin (Hb), red blood cells (RBC), and platelet (PLT) count. In addition, blood superoxide dismutase (SOD) and urinary level of 8 hydroxydeoxyguanosine (8-OHdG) were evaluated to determine the oxidative stress and DNA damage, respectively. A questionnaire was used to document demographic-, health-, and exposure-related information. The results showed that urinary beta naphthol was almost 44% higher in WR subjects than WC (median 7.69 vs. 3.39 MUmol/mol-Cr, respectively; p = 0.01) and respective controls (CF). Higher urinary 8-OHdG were observed in WR (71.1 ng/mg-Cr) than WC (56.37 ng/mg-Cr) (p < 0.001), and lower life status and higher degree of headache were observed in WR than WC. In WCs, however, a low Hb and high WBC (8.29 * 10(3) MUL(-1), ranging between 6.1 and 10.6 * 10(3) MUL(-1)) were observed in comparison with CM. The study shows that WC subjects used larger amount of fuel and were subjected to prolonged exposure. It was concluded that the role of ventilation is fundamental and WR were more exposed to PAHs despite the fact that WC spent more time in cooking (due to occupational requirement) than WR. PMID- 26358215 TI - Pb pollution in soils from a trap shooting range and the phytoremediation ability of Agrostis capillaris L. AB - Pb pollution caused by shooting sport activities is a serious environmental problem that has increased considerably in recent decades. The aims of this study were firstly to analyze Pb pollution in soils from a trap shooting range abandoned in 1999, secondly to study the effectiveness of different extractants [CaCl2, DTPA, NH4OAc, low molecular weight organic acids (LMWOA), and bidistilled water (BDW)] in order to determine Pb bioavailability in these soils, and finally to evaluate the phytoremediation ability of spontaneous vegetation (Agrostis capillaris L.). To this end, 13 soils from an old trap shooting range (Galicia, NW Spain) were studied. It was found that Pb levels in the soils were higher than 100 mg kg(-1), exceeding the generic reference levels, and three of these samples even exceeded the USEPA threshold level (400 mg kg(-1)). In general, the reagent that best represents Pb bioavailability and has the greatest extraction efficiency was CaCl2, followed by DTPA, NH4OAc, LMWOA, and BDW. A. capillaris Pb contents ranged between 9.82 and 1107.42 mg kg(-1) (root) and between 6.43 and 135.23 mg kg(-1) (shoot). Pb accumulation in roots, as well as the presence of secondary mineral phases of metallic Pb in the adjacent soil, showed the phytostabilization properties of A. capillaris. PMID- 26358216 TI - Influence of natural zeolite and nitrification inhibitor on organics degradation and nitrogen transformation during sludge composting. AB - Sludge composting is one of the most widely used treatments for sewage sludge resource utilization. Natural zeolite and nitrification inhibitor (NI) are widely used during composting and land application for nitrogen conservation, respectively. Three composting reactors (A--the control, B--natural zeolite addition, and C--3,4-dimethylpyrazole phosphate (DMPP) addition) were established to investigate the influence of NI and natural zeolite addition on organics degradation and nitrogen transformation during sludge composting conducted at the lab scale. The results showed that, in comparison with the control, natural zeolite addition accelerated organics degradation and the maturity of sludge compost was higher, while the DMPP addition slowed down the degradation of organic matters. Meanwhile, the nitrogen transformation functional genes including those responses for nitrification (amoA and nxrA) and denitrification (narG, nirS, nirK, and nosZ) were quantified through quantitative PCR (qPCR) to investigate the effects of natural zeolites and DMPP addition on nitrogen transformation. Although no significant difference in the abundance of nitrogen transformation functional genes was observed between treatments, addition of both natural zeolite and DMPP increases the final total nitrogen content by 48.6% and 23.1%, respectively. The ability of natural zeolite for nitrogen conservation was due to the absorption of NH3 by compost, and nitrogen conservation by DMPP was achieved by the source reduction of denitrification. Besides, it was assumed that the addition of natural zeolite and DMPP may affect the activity of these genes instead of the abundance. PMID- 26358217 TI - Oxidative damage induced by copper in mouse primary hepatocytes by single-cell analysis. AB - Copper can disturb the intracellular redox balance, induce oxidative stress, and subsequently cause irreversible damage, leading to a variety of diseases. In the present study, mouse primary hepatocytes were chosen to elucidate the in vitro oxidative damage of short-term copper exposure (10-200 MUM) by single-cell analysis. We evaluated the toxicity of copper by reactive oxygen species (ROS), glutathione (GSH), and oxidative DNA damage at the single-cell level. Oxidative damage induced by copper was verified by the morphological changes, persistent elevations of excessive ROS and malondialdehyde (MDA), a decrease in GSH level, and the oxidative DNA damage. Furthermore, the average ROS generation, GSH consumption, and the indicators in DNA damage did not significantly change at relatively low concentrations (10 or 50 MUM), but we can find the alterations of parameters in some single cells clearly. Emphasis on the analysis of single cells is conducive to gain a better understanding on the toxicity of copper. This study will also complement studies on the environmental risk assessment of copper pollution. PMID- 26358218 TI - Mutations affecting domain V of the 23S rRNA gene in Helicobacter pylori from Cairo, Egypt. AB - BACKGROUND: Clarithromycin is a main component of the recommended first-line triple therapy for Helicobacter pylori in Egypt. We aimed in our study to investigate the prevalence of clarithromycin-resistant H. pylori strains due to the point mutations at domain V of the H. pylori 23S rRNA among the Egyptian population using the polymerase chain reaction/restricted fragment length polymorphism (PCR/RFLP) assay. METHODS: Gastric biopsies obtained from 100 dyspeptic patients who consecutively attended at Cairo University Hospital during the period from January to November 2013 were subjected to PCR/RFLP in order to detect the point mutations at domain V of the H. pylori 23S rRNA associated with clarithromycin resistance. The PCR amplicon of the 23S H. pylori rRNA is restricted with MboII for detection of A2142G mutation and with BsaI for A2143G mutation. RESULTS: The prevalence of H. pylori infection among 100 patients was 70%; clarithromycin resistance was detected in 39/70 (57.7%) of positive H. pylori isolates. Occurrence of 23S rRNA A2142G mutations resulted in two DNA fragments (418 and 350 bp) by PCR-RFLP; on the other hand, no A2143G mutations were detected. CONCLUSIONS: The high prevalence of clarithromycin resistance (57.7%) caused by A2142G mutations at domain V of the H. pylori 23S rRNA may mandate changing of the standard clarithromycin-containing triple therapy. The PCR/RFLP assay was a rapid and accurate method for molecular detection of H. pylori infection in addition to determination of different nucleotide mutations causing clarithromycin resistance. PMID- 26358220 TI - Histamine released from epidermal keratinocytes plays a role in alpha-melanocyte stimulating hormone-induced itching in mice. AB - Sunburn, wound repair, and chronic renal failure with hemodialysis are usually accompanied by both pigmentation and itching. Proopiomelanocortin-derived alpha melanocyte-stimulating hormone (alpha-MSH) is produced in response to external stimuli, such as UV irradiation, and is involved in cutaneous pigmentation. However, it is unclear whether alpha-MSH is also involved in the itching. We therefore investigated whether alpha-MSH elicited itch-related responses in mice. We found that an intradermal injection of alpha-MSH induced hind-paw scratching, an itch-related response, in mice. The alpha-MSH-induced scratching was inhibited by the MU-opioid receptor antagonist naltrexone and the H1 histamine receptor antagonist terfenadine. In mast cell-deficient mice, alpha-MSH also elicited scratching, which was inhibited by terfenadine. The immunoreactivity for l histidine decarboxylase, a key enzyme required for the production of histamine, histamine, and the melanocortin 1 and 5 receptors were shown in not only mast cells but also keratinocytes in murine skin. In addition to the expression of l histidine decarboxylase and melanocortin 1 and 5 receptors, the mouse keratinocyte cell lines (Pam212) also showed immunoreactivity for l-histidine decarboxylase, histamine, and melanocortin 1 and 5 receptors. The application of alpha-MSH induced the release of histamine from Pam212 cells. These findings indicate that alpha-MSH may play an important role in the itching associated with pigmented cutaneous lesions and that the histamine released from keratinocytes is involved in this alpha-MSH-induced itching. PMID- 26358219 TI - Mesenchymal deficiency of Notch1 attenuates bleomycin-induced pulmonary fibrosis. AB - Notch signaling pathway is involved in the regulation of cell fate, differentiation, proliferation, and apoptosis in development and disease. Previous studies suggest the importance of Notch1 in myofibroblast differentiation in lung alveogenesis and fibrosis. However, direct in vivo evidence of Notch1-mediated myofibroblast differentiation is lacking. In this study, we examined the effects of conditional mesenchymal-specific deletion of Notch1 on pulmonary fibrosis. Crossing of mice bearing the floxed Notch1 gene with alpha2(I) collagen enhancer-Cre-ER(T)-bearing mice successfully generated progeny with a conditional knockout (CKO) of Notch1 in collagen I-expressing (mesenchymal) cells on treatment with tamoxifen (Notch1 CKO). Because Notch signaling is known to be activated in the bleomycin model of pulmonary fibrosis, control and Notch1 CKO mice were analyzed for their responses to bleomycin treatment. The results showed significant attenuation of pulmonary fibrosis in CKO relative to control mice, as examined by collagen deposition, myofibroblast differentiation, and histopathology. However, there were no significant differences in inflammatory or immune cell influx between bleomycin-treated CKO and control mouse lungs. Analysis of isolated lung fibroblasts confirmed absence of Notch1 expression in cells from CKO mice, which contained fewer myofibroblasts and significantly diminished collagen I expression relative to those from control mice. These findings revealed an essential role for Notch1-mediated myofibroblast differentiation in the pathogenesis of pulmonary fibrosis. PMID- 26358221 TI - TNF-alpha-induced p38MAPK activation regulates TRPA1 and TRPV4 activity in odontoblast-like cells. AB - The transient receptor potential (TRP) channels are unique cellular sensors that are widely expressed in many neuronal and nonneuronal cells. Among the TRP family members, TRPA1 and TRPV4 are emerging as candidate mechanosensitive channels that play a pivotal role in inflammatory pain and mechanical hyperalgesia. Odontoblasts are nonneuronal cells that possess many of the features of mechanosensitive cells and mediate important defense and sensory functions. However, the effect of inflammation on the activity of the odontoblast's mechanosensitive channels remains unknown. By using immunohistochemistry and calcium microfluorimetry, we showed that odontoblast-like cells express TRPA1 and TRPV4 and that these channels were activated by hypotonicity-induced membrane stretch. Short treatment of odontoblast-like cells with tumor necrosis factor (TNF)-alpha enhanced TRPA1 and TRPV4 responses to their chemical agonists and membrane stretch. This enhanced channel activity was accompanied by phospho-p38 mitogen-activated protein kinase (MAPK) expression. Treatment of cells with the p38 inhibitor SB202190 reduced TNF-alpha effects, suggesting modulation of channel activity via p38 MAPK. In addition, TNF-alpha treatment also resulted in an up-regulation of TRPA1 expression but down-regulation of TRPV4. Unlike TRPV4, enhanced TRPA1 expression was also evident in dental pulp of carious compared with noncarious teeth. SB202190 treatment significantly reduced TNF-alpha-induced TRPA1 expression, suggesting a role for p38 MAPK signaling in modulating both the transcriptional and non-transcriptional regulation of TRP channels in odontoblasts. PMID- 26358222 TI - Vaccination with Klebsiella pneumoniae-derived extracellular vesicles protects against bacteria-induced lethality via both humoral and cellular immunity. AB - The emergence of multidrug-resistant Klebsiella pneumoniae highlights the need to develop preventive measures to ameliorate Klebsiella infections. Bacteria-derived extracellular vesicles (EVs) are spherical nanometer-sized proteolipids enriched with outer membrane proteins. Gram-negative bacteria-derived EVs have gained interest for use as nonliving complex vaccines. In the present study, we evaluated whether K. pneumoniae-derived EVs confer protection against bacteria induced lethality. K. pneumoniae-derived EVs isolated from in vitro bacterial culture supernatants induced innate immunity, including the upregulation of co stimulatory molecule expression and proinflammatory mediator production. EV vaccination via the intraperitoneal route elicited EV-reactive antibodies and interferon-gamma-producing T-cell responses. Three vaccinations with the EVs prevented bacteria-induced lethality. As verified by sera and splenocytes adoptive transfer, the protective effect of EV vaccination was dependent on both humoral and cellular immunity. Taken together, these findings suggest that K. pneumoniae-derived EVs are a novel vaccine candidate against K. pneumoniae infections. PMID- 26358224 TI - Measuring oxygen uptake in fishes with bimodal respiration. AB - Respirometry is a robust method for measurement of oxygen uptake as a proxy for metabolic rate in fishes, and how species with bimodal respiration might meet their demands from water v. air has interested researchers for over a century. The challenges of measuring oxygen uptake from both water and air, preferably simultaneously, have been addressed in a variety of ways, which are briefly reviewed. These methods are not well-suited for the long-term measurements necessary to be certain of obtaining undisturbed patterns of respiratory partitioning, for example, to estimate traits such as standard metabolic rate. Such measurements require automated intermittent-closed respirometry that, for bimodal fishes, has only recently been developed. This paper describes two approaches in enough detail to be replicated by the interested researcher. These methods are for static respirometry. Measuring oxygen uptake by bimodal fishes during exercise poses specific challenges, which are described to aid the reader in designing experiments. The respiratory physiology and behaviour of air breathing fishes is very complex and can easily be influenced by experimental conditions, and some general considerations are listed to facilitate the design of experiments. Air breathing is believed to have evolved in response to aquatic hypoxia and, probably, associated hypercapnia. The review ends by considering what realistic hypercapnia is, how hypercapnic tropical waters can become and how this might influence bimodal animals' gas exchange. PMID- 26358223 TI - A comprehensive investigation on the distribution of circulating follicular T helper cells and B cell subsets in primary Sjogren's syndrome and systemic lupus erythematosus. AB - Follicular T helper (Tfh) cells have a crucial role in regulating immune responses within secondary lymphoid follicles by directing B cell differentiation towards memory B cells and plasma cells. Because abnormal humoral responses are key features in both primary Sjogren's syndrome (pSS) and systemic lupus erythematosus (SLE), the aim of this study was to profile the pathological connection between peripheral Tfh cells and B cells in the two diseases. Twenty five pSS patients, 25 SLE patients and 21 healthy controls were enrolled into the study. We determined the ratio of circulating Tfh-like cells, their interleukin (IL)-21 production and different B cell subsets by flow cytometry. We observed higher percentages of naive B cells in both diseases, while non-switched and switched memory B cells showed decreased frequencies. The proportions of double negative B cells and plasmablasts were elevated in SLE and decreased in pSS. The percentages of transitional B cells and mature-naive B cells were higher in SLE. Patients with more severe disease course had an elevated ratio of TFH-like cells and increased IL-21 production. Moreover, expansion of Tfh-like cells correlated positively with parameters related to antibody secretion, including serum immunoglobulin (Ig)G, immune complexes (ICs) and autoantibodies. Correlation analysis between Tfh-like cells and certain B cell subsets revealed possible defects during B cell selection. In conclusion, our observations on the profound expansion of circulating Tfh-like cells and their IL-21 production, along with the characteristic aberrant peripheral B cell distribution in both pSS and SLE, indicate the prominent role of Tfh cell in the regulation of B cell selection. PMID- 26358225 TI - Factor analysis for genetic evaluation of linear type traits in dual-purpose autochthonous breeds. AB - Factor analysis was applied to individual type traits (TT) scored in primiparous cows belonging to two dual purpose Italian breeds, Rendena (REN; 20 individual type traits evaluated on 11 399 first parity cows), and Aosta Red Pied (ARP; 22 individual type traits evaluated on 36 168 primiparous cows). Six common latent factors (F1 to F6; eigenvalues ?1) which explained 63% (REN) and 58% (ARP) of the total variance were obtained. F1 included TT mainly related to muscularity, and F2 to body size. The F3 and F4 accounted for udder size and conformation, respectively. F5 included rear legs and feet. Biological significance for F6 was not readily obtained. Moderate to low heritability were estimated through REML single-trait analysis from factor scores (from 0.22 to 0.52 in REN, and from 0.08 to 0.37 in ARP). The greatest heritability values were estimated for body size and muscularity (0.52 and 0.37 for body size; and 0.40 and 0.32 for muscularity in REN and ARP, respectively). As expected, rank correlations, obtained considering estimated breeding values derived from best linear unbiased prediction analysis on the individual TT and factor score, showed similar coefficients to those observed in the factor analysis following loading of TT within each latent factor. These results suggest the possibility to implement the factor analysis in the morphological evaluation, simplifying the information given by the type traits into new variables useful for the genetic improvement of dual purpose cattle. PMID- 26358226 TI - Cardioprotective function of mitochondrial-targeted and transcriptionally inactive STAT3 against ischemia and reperfusion injury. AB - Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that contributes a crucial role in protection against ischemia (ISC) reperfusion (REP) injury by driving expression of anti-apoptotic and anti-oxidant genes. STAT3 is also present in the mitochondria, where it modulates the activity of the electron transport chain (ETC) and the permeability transition pore. Transgenic mice that overexpress a mitochondrial-targeted, transcriptionally inactive STAT3 in cardiomyocytes (MLS-STAT3E mice) exhibit a persistent, partial blockade of electron transfer through complex I that uniquely did not lead to tissue dysfunction at baseline, yet increased mitochondrial ischemic tolerance. The direct contribution of non-transcriptional, mitochondria-localized STAT3 to protection during ISC-REP remains to be established. We hypothesized that the enhanced mitochondrial tolerance to ischemia present in MLS-STAT3E mice would decrease cardiac injury during ISC-REP. In the isolated buffer-perfused heart model, MLS-STAT3E hearts exhibit a decreased infarct size compared to non transgenic littermate hearts. Contractile recovery, expressed as a percent of LV developed pressure before ISC, is improved in MLS-STAT3E mice. Mitochondria isolated at the end of 60 min. of REP from MLS-STAT3E hearts show attenuated ROS release. The partial and persistent blockade of complex I present in MLS-STAT3E mice decreases cardiac injury during REP, in part via a persistent decrease in ROS production and attenuation of mitochondrial permeability transition pore opening at the onset of REP. In vivo, MLS-STAT3E hearts exhibit substantially higher postoperative survival rate and a substantial decrease in myocardial infarct size. STAT3 mediates cardioprotection not only via canonical action as a transcription factor, but also as a modulator of ETC activity directly in the mitochondria. PMID- 26358227 TI - Improvement of dyskinesias with L-dopa infusion in advanced Parkinson's disease. AB - OBJECTIVES: We wanted to investigate whether continuous intrajejunal levodopa carbidopa intestinal gel (LCIG) therapy has an antidyskinetic effect in patients with Parkinson's disease (PD) and troublesome dyskinesias. We also sought to examine the effect of LCIG therapy on motor function and health-related quality of life (HRQoL). MATERIALS AND METHODS: This open-label pilot study used a single group pre-post design with follow-up at 6 months. Nine patients with PD who reported to spend at least 3 h per day in on with troublesome dyskinesia were included. The patients were examined at baseline using clinical and self assessment measures and then switched from peroral/transdermal pharmacotherapy to LCIG therapy. Data collection was repeated 6 months after the pharmaceutical intervention. Nonparametric statistical methods were used for data analyses. RESULTS: The mean time spent in on with troublesome dyskinesia per day after 6 months of LCIG therapy decreased by 47% (P < 0.05). This observation was paralleled by a 112% increase in mean time spent in on without troublesome dyskinesia (P < 0.01). Patient self-assessment of dyskinesia intensity on the visual analog scale displayed a 90% reduction of mean dyskinesia intensity (P < 0.01) and patients also exhibited less dyskinesia during standardized levodopa tests. Furthermore, we noted improvements in motor function and HRQoL. CONCLUSIONS: In this pilot study, we found indications that LCIG therapy has a substantial antidyskinetic effect and could be an alternative also for PD patients with dyskinesias as a major symptom. However, further studies with blinded evaluation and larger numbers of patients are warranted to confirm the findings. PMID- 26358228 TI - How to Be a Pioneer: A One-Sided View. PMID- 26358229 TI - Characteristics of Cerebrovascular Injury in the Hyperacute Phase After Induced Severe Subarachnoid Hemorrhage. AB - Although there have been several investigations regarding acute brain injury after subarachnoid hemorrhage (SAH), the pathological conditions of severe SAH are unclear. In this study, we pursued the characteristics of cerebrovascular injury in the hyperacute phase after experimentally induced severe SAH. Twenty three male Sprague-Dawley rats were subjected to sham or SAH operation using the endovascular perforation method and were evaluated for brain edema, blood-brain barrier (BBB) permeability, and arterial endothelial cell injury at 5 min after SAH (experiment 1). Next, animals were examined for functional and morphological changes of cerebral artery for 30 min after an acetazolamide injection administered 5 min after SAH (experiment 2). In experiment 1, while cerebral blood flow (CBF) was reduced, brain edema was not observed in SAH-operated rats. BBB permeability detected by immunoglobulin G extravasation was observed in the optic tract and was accompanied by the upregulation of phosphorylated extracellular signal-regulated kinase (ERK)-positive astrocytes. In addition, the number of phosphorylated ERK-positive endothelial cell in the distal middle cerebral artery (MCA) was significantly increased by SAH. In experiment 2, CBF in non-lethal SAH rats was reduced, and no response to acetazolamide was detected. Conversely, CBF in lethal SAH increased due to acetazolamide, although the value of CBF was low. Furthermore, there was significant narrowing of the MCA in SAH operated rats. The findings suggest that the optic tract and the cerebral artery are the most vulnerable areas regarding cerebrovascular injury in a hyperacute phase after severe SAH and that they are associated with fatal outcomes. PMID- 26358230 TI - Pharmaceutical compositions for antihypertensive treatments: a patent review. AB - INTRODUCTION: New drug formulations against hypertension have a vital role in the quality of human life, as this risk factor for cardiovascular disease can be life threatening. A modern life style characterized by less exercise, smoking, drinking and poor diet has increased the risk of developing hypertension, the so called silent killer, in civilized communities and thus an urgent defense is needed against this enemy. AREAS COVERED: In this review, the authors provide extensive information on pharmaceutical formulations containing anti-hypertensive drugs, as well as on general and specific patents. Thus, readers can understand the advances and new trends in the field. EXPERT OPINION: A considerable effort has been made to provide new and improved formulations, comprising anti hypertensive drugs with new excipients, appropriate particle size, containing alkaline salts or included in cyclodextrins in an attempt to avoid known existing problems. New types of formulations are expected to emerge in the near future that will allow for more effective and spatiotemporally controlled drug delivery, which will be better tolerated by the patients and will provide better pharmaceutical treatment. Such an example is the new cocktail formulations that contain more than one active component, act synergistically and therefore have optimized pharmacological benefits. Formulations using multitarget antihypertensive drugs are also expected to be commercially available in the near future. PMID- 26358231 TI - Urinary tract infection in infants: the significance of low bacterial count. AB - BACKGROUND: In national guidelines for urinary tract infection (UTI) in children, different cut-off levels for defining bacteriuria are used. In this study, the relationship between bacterial count in infant UTI and inflammatory parameters, frequency of vesicoureteral reflux (VUR), kidney damage, and recurrent UTI was analyzed. METHODS: We conducted a population-based retrospective study of 430 infants age <1 year with symptomatic UTI diagnosed by suprapubic aspiration. Clinical and laboratory parameters, findings on voiding cystourethrography and (99m)technetium dimercapto-succinic acid scintigraphy, and frequency of recurrence were related to bacterial count at the index UTI. RESULTS: Eighty three (19%) infants had bacterial counts <100,000 colony-forming units (CFU)/ml and 347 (81%) had >=100,000 CFU/ml. There was similar frequency of VUR (19% in both groups), kidney damage (17 and 23%, p = 0.33) and recurrent UTI (6 and 12%, p = 0.17) in the low and high bacterial group. Non-E. coli species were more prevalent (19 versus 6%, p = 0.0006) and mean C-reactive protein was lower (50 vs. 79 mg/l, p <0.0001) in the low bacteria group. CONCLUSIONS: UTI with low bacterial count is common and of importance since it may be associated with VUR and renal damage. Non-E. coli species and low inflammatory response were more prevalent in UTI with low bacterial count. PMID- 26358232 TI - A fractal analysis of the spatial distribution of tumoral mast cells in lymph nodes and bone marrow. AB - The spatial distribution of mast cells inside the tumor stroma has been little investigated. In this study, we have evaluated tumor mast cells distribution through the analysis of the morphological features of the spatial patterns generated by these cells, including size, shape, and architecture of the cell pattern. We have compared diffuse large B cells lymphoma (DLBCL) and systemic mastocytosis in two different anatomical localizations (lymph nodes for DLBCL and, respectively, bone marrow for mastocytosis). Results have indicated that, despite the high difference in size exhibited by the mast cells patterns in the two conditions, the spatial relationship between the mast cells forming the aggregates resulted similar, characterized by a significant tendency of the mast cells to self-organize in clusters. PMID- 26358233 TI - PEP-1-SIRT2 causes dedifferentiation and COX-2 expression via the MAPK pathways in rabbit articular chondrocytes. AB - SIRT2 is a member of the mammalian sirtuin protein family, primarily found in the cytoplasm. It regulates numerous cellular processes including aging, DNA repair, cell cycle, and survival under stress conditions. However, the biological function and mechanism of the SIRT2 protein was not well understood in normal cells such as primary chondrocytes. In this study, we examined the effects of SIRT2 on differentiation and inflammation in rabbit articular chondrocytes by using a cell-permeative PEP-1-SIRT2 protein. Our results indicate that PEP-1 SIRT2-induced a loss of type II collagen and decreased sulfate proteoglycan levels in a dose- and time-dependent manner, as examined by Western blotting, alcian blue staining, and immunohistochemistry. Furthermore, PEP-1-SIRT2 caused an inflammatory response by inducing the expression of cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2). In addition, after treatment with PEP-1-SIRT2, phosphorylation of both p38 and ERK was observed. Inhibition of ERK with PD98059 (PD) suppressed PEP-1-SIRT2-induced dedifferentiation and COX-2 expression. Reduction in PEP-1-SIRT2-induced inflammatory response was observed upon inhibition of p38 by SB203580 (SB). The same pattern was demonstrated in PEP-1 SIRT2-induced dedifferentiation and inflammatory response during culture with serial passages. During expansion to four passages, levels of type II collagen decreased, whereas levels of COX-2 and SIRT2 increased and activated ERK and p38. Furthermore, PEP-1-SIRT2 enhances dedifferentiation through the ERK pathway and inflammatory response through the ERK and p38 pathways in rabbit chondrocytes in vitro. These findings suggest that PEP-1-SIRT2 induces dedifferentiation via the ERK pathway and inflammation through the p38 and ERK pathways in rabbit articular chondrocytes. PMID- 26358234 TI - Response to: 'Comment on The Eye Phone Study: reliability and accuracy of assessing Snellen visual acuity using smartphone technology'. PMID- 26358235 TI - A novel eye drop application monitor to assess patient compliance with a prescribed regimen: a pilot study. AB - PURPOSE: To assess the ability of a novel imaging device to allow physicians to personalize therapeutic regimens based on objective patient drop administration data. METHODS: A novel imaging system was used to record video of the drop technique of subjects in clinic (n=25) or at home (n=17) for 1 week. Video assessment by a reading center was compared with patient reporting and their prescribed regimen with respect to how many drops were applied and how many landed in the eye. RESULTS: Reading center assessment of both drops dispensed and drops landing in the eye was significantly different from the prescribed regimen in the clinic (Pd=0.005, Pi<0.001, respectively) and at-home arms (Pd=0.003, Pi<0.001, respectively). CONCLUSIONS: This imaging system is a powerful tool to help physicians tailor patient therapy more accurately, to help researchers evaluate new drop therapies with objective rather than subjective data, and to potentially facilitate better patient training for improved drug delivery. PMID- 26358236 TI - Comment on 'The Eye Phone Study: reliability and accuracy of assessing Snellen visual acuity using smartphone technology'. PMID- 26358237 TI - Comparison of circulating lipid profiles between fasting humans and three animal species used in preclinical studies: mice, rats and rabbits. AB - BACKGROUND: Circulating lipid metabolites are associated with many physiological and biological processes in the body, and therefore could be used as biomarkers for evaluating drug efficacy and safety in preclinical studies. However, differences in circulating lipid profiles among humans and animals often used in preclinical studies have not been fully investigated. METHODS: We performed lipidomic analysis to obtain circulating lipid profiles of fasted humans (Caucasian, n = 15) and three animal species used in preclinical studies (mice [BALB/c, n = 5], rats [Sprague-Dawley, n = 5], and rabbits [New Zealand White, n = 5]) by using liquid chromatography-mass spectrometry. RESULTS: Our data showed marked differences in lipid profiles among humans and these animal species. Furthermore, we observed that the levels of many lipid metabolites, such as poly unsaturated fatty acid-containing cholesteryl esters, ether-type phosphoglycerolipids, and sulfatides, were significantly different (p < 0.05) by more than 10-fold in these animals (depending on the animal species) from humans. CONCLUSION: Our data could be useful while extrapolating the data on the biomarker candidates identified in preclinical studies into clinical studies. PMID- 26358238 TI - Physiology, production and action of progesterone. AB - INTRODUCTION: The aim of this article is to review the physiology of progesterone and focus on its physiological actions on tissues such as endometrium, uterus, mammary gland, cardiovascular system, central nervous system and bones. In the last decades, the interest of researchers has focused on the role of progesterone in genomic and non-genomic receptor mechanisms. MATERIALS AND METHODS: We searched PubMed up to December 2014 for publications on progesterone/steroidogenesis. RESULTS AND CONCLUSIONS: A better understanding of the biological genomic and non-genomic receptor mechanisms could enable us in the near future to obtain a more comprehensive knowledge of the safety and efficacy of this agent during hormone replacement therapy (natural progesterone), in vitro fertilization (water-soluble subcutaneous progesterone), in traumatic brain injury, Alzheimer's disease and diabetic neuropathy, even though further clinical studies are needed to prove its usefulness. PMID- 26358239 TI - Success and failure assessing gonad maturity in sequentially hermaphroditic fishes: comparisons between macroscopic and microscopic methods. AB - For two protogynous hermaphrodite fish species, the performance of visual gonad analysis techniques was evaluated to determine when the use of macroscopic methods was sufficient and when microscopic techniques were necessary. Simple macroscopic gonad analysis was found to be a powerful tool for distinguishing sex and whether or not females were spawning capable or ripe for black sea bass Centropristis striata (n = 1443) and red porgy Pagrus pagrus (n = 980), often producing results that were in close agreement with more complex and expensive microscopic techniques. Estimates of key reproductive variables, such as size dependent sex-change ogives, spawning season duration, spawning fraction and batch number, were also very similar or equal between methods. Apparent seasonal spawning activity was also predicted similarly by each method and the patterns were highly correlated with seasonal patterns in gonado-somatic indices. In contrast, distinguishing between immature females and those that were mature, but inactive, proved difficult when using macroscopic methods and, in these cases, predictions often differed from those produced microscopically. In turn, maturity ogives differed significantly between methods for C. striata (maturity ogives could not be generated for P. pagrus as nearly all fish encountered were mature). Agreement rates among male phases were also very low. Macroscopic methods were able to identify signs of sex transition in very advanced specimens, but early signs were only evident microscopically. While much more detail is visible microscopically, here several population-scale parameters important for fisheries management were estimated equally well with the unaided eye for C. striata and P. pagrus. For comprehensive, fishery-independent surveys and long-term research programmes in particular, determining when microscopic techniques are and are not necessary can greatly improve efficiency and reduce costs without compromising data quality. PMID- 26358240 TI - Risk factors affecting child cognitive development: a summary of nutrition, environment, and maternal-child interaction indicators for sub-Saharan Africa. AB - An estimated 200 million children worldwide fail to meet their development potential due to poverty, poor health and unstimulating environments. Missing developmental milestones has lasting effects on adult human capital. Africa has a large burden of risk factors for poor child development. The objective of this paper is to identify scope for improvement at the country level in three domains- nutrition, environment, and mother-child interactions. We used nationally representative data from large-scale surveys, data repositories and country reports from 2000 to 2014. Overall, there was heterogeneity in performance across domains, suggesting that each country faces distinct challenges in addressing risk factors for poor child development. Data were lacking for many indicators, especially in the mother-child interaction domain. There is a clear need to improve routine collection of high-quality, country-level indicators relevant to child development to assess risk and track progress. PMID- 26358241 TI - Separation of Doppler radar-based respiratory signatures. AB - Respiration detection using microwave Doppler radar has attracted significant interest primarily due to its unobtrusive form of measurement. With less preparation in comparison with attaching physical sensors on the body or wearing special clothing, Doppler radar for respiration detection and monitoring is particularly useful for long-term monitoring applications such as sleep studies (i.e. sleep apnoea, SIDS). However, motion artefacts and interference from multiple sources limit the widespread use and the scope of potential applications of this technique. Utilising the recent advances in independent component analysis (ICA) and multiple antenna configuration schemes, this work investigates the feasibility of decomposing respiratory signatures into each subject from the Doppler-based measurements. Experimental results demonstrated that FastICA is capable of separating two distinct respiratory signatures from two subjects adjacent to each other even in the presence of apnoea. In each test scenario, the separated respiratory patterns correlate closely to the reference respiration strap readings. The effectiveness of FastICA in dealing with the mixed Doppler radar respiration signals confirms its applicability in healthcare applications, especially in long-term home-based monitoring as it usually involves at least two people in the same environment (i.e. two people sleeping next to each other). Further, the use of FastICA to separate involuntary movements such as the arm swing from the respiratory signatures of a single subject was explored in a multiple antenna environment. The separated respiratory signal indeed demonstrated a high correlation with the measurements made by a respiratory strap used currently in clinical settings. PMID- 26358242 TI - Characterization of high capacitance electrodes for the application of direct current electrical nerve block. AB - Direct current (DC) can briefly produce a reversible nerve conduction block in acute experiments. However, irreversible reactions at the electrode-tissue interface have prevented its use in both acute and chronic settings. A high capacitance material (platinum black) using a charge-balanced waveform was evaluated to determine whether brief DC block (13 s) could be achieved repeatedly (>100 cycles) without causing acute irreversible reduction in nerve conduction. Electrochemical techniques were used to characterize the electrodes to determine appropriate waveform parameters. In vivo experiments on DC motor conduction block of the rat sciatic nerve were performed to characterize the acute neural response to this novel nerve block system. Complete nerve motor conduction block of the rat sciatic nerve was possible in all experiments, with the block threshold ranging from -0.15 to -3.0 mA. DC pulses were applied for 100 cycles with no nerve conduction reduction in four of the six platinum black electrodes tested. However, two of the six electrodes exhibited irreversible conduction degradation despite charge delivery that was within the initial Q (capacitance) value of the electrode. Degradation of material properties occurred in all experiments, pointing to a possible cause of the reduction in nerve conduction in some platinum black experiments . PMID- 26358243 TI - Effects of reconstructed magnetic field from sparse noisy boundary measurements on localization of active neural source. AB - Localization of active neural source (ANS) from measurements on head surface is vital in magnetoencephalography. As neuron-generated magnetic fields are extremely weak, significant uncertainties caused by stochastic measurement interference complicate its localization. This paper presents a novel computational method based on reconstructed magnetic field from sparse noisy measurements for enhanced ANS localization by suppressing effects of unrelated noise. In this approach, the magnetic flux density (MFD) in the nearby current free space outside the head is reconstructed from measurements through formulating the infinite series solution of the Laplace's equation, where boundary condition (BC) integrals over the entire measurements provide "smooth" reconstructed MFD with the decrease in unrelated noise. Using a gradient-based method, reconstructed MFDs with good fidelity are selected for enhanced ANS localization. The reconstruction model, spatial interpolation of BC, parametric equivalent current dipole-based inverse estimation algorithm using reconstruction, and gradient-based selection are detailed and validated. The influences of various source depths and measurement signal-to-noise ratio levels on the estimated ANS location are analyzed numerically and compared with a traditional method (where measurements are directly used), and it was demonstrated that gradient-selected high-fidelity reconstructed data can effectively improve the accuracy of ANS localization. PMID- 26358244 TI - Kinematics of passive flexion following balanced and overstuffed fixed bearing unicondylar knee arthroplasty. AB - INTRODUCTION: Progression of osteoarthritis in the unreplaced compartment following unicondylar knee arthroplasty (UKA) may be hastened if kinematics is disturbed following UKA implantation. The purpose of this study was to analyze tibiofemoral kinematics of the balanced and overstuffed UKA in comparison with the native knee during passive flexion since this is a common clinical assessment. METHODS: Ten cadaveric knees were mounted to robotic manipulator and underwent passive flexion from 0 to 90 degrees . The kinematic pathway was recorded in the native knee and in the balanced, fixed bearing UKA. The medial UKA was implanted using a measured resection technique. Additionally, a one millimeter thicker tibial insert was installed to simulate the effects of overstuffing. Tibial kinematics in relation to the femur was recorded. RESULTS: Following UKA the tibia was externally rotated, and in valgus relative to the native knee near extension. In flexion, installing the UKA caused the knee to be translated medially and anteriorly. The tibia was translated distally through the entire range of flexion after UKA. Compared to the balanced UKA, overstuffing further increased valgus at full extension and distal translation of the tibia from full extension to 45 degrees flexion. CONCLUSIONS: UKA implantation altered tibiofemoral kinematics in all planes. Differences were small; nevertheless, they may affect tibiofemoral loading patterns. CLINICAL RELEVANCE: Alterations in tibiofemoral kinematics following UKA might have implications for prosthesis failure and progression of osteoarthritis in the remaining compartment. Overstuffing should be avoided as it further increased valgus and did not improve the remaining kinematics. PMID- 26358245 TI - Mapping the governance of human resources for health in Serbia. AB - This article maps the current governance of human resources for health (HRH) in relation to universal health coverage in Serbia since the health sector reforms in 2003. The study adapts the Global Health Workforce Alliance/World Health Organization four-dimensional framework of HRH in the context of governance for universal health coverage. A set of proxies was established for the availability, accessibility, acceptability and quality of HRH. Analysis of official HRH documentation from relevant institutions and reports were used to construct a governance profile of HRH for Serbia from the introduction of the reform in 2003 up to 2013. The results show that all Serbian districts (except Sremski) surpass the availability threshold of 59.4 skilled midwives, nurses and physicians per 10,000 inhabitants. District accessibility of health workforce greatly differed from the national average with variances from +26% to -34%. Analysis of national averages and patient load of general practitioners showed variances among districts by +/- 21%, whilst hospital discharges per 100 inhabitants deviated between +52% and -45%. Pre-service and in-service education of health workforce is regulated and accredited. However, through its efforts to respond to population health needs Serbia lacks a single coordinating entity to take overall responsibility for effective and coordinated HRH planning, management and development within the broader landscape of health strategy development. PMID- 26358246 TI - Enumerating the preventive youth health care workforce: Size, composition and regional variation in the Netherlands. AB - The progress in workforce planning in preventive youth health care (YHC) is hampered by a lack of data on the current workforce. This study aimed to enumerate the Dutch YHC workforce. To understand regional variations in workforce capacity we compared these with the workforce capacity and the number of children and indicators of YHC need per region. A national survey was conducted using online questionnaires based on WHO essential public health operations among all YHC workers. Respondents (n=3220) were recruited through organisations involved in YHC (participation: 88%). The YHC workforce is multi-disciplinary, 62% had >10 years working experience within YHC and only small regional variations in composition existed. The number of children per YHC professional varied between regions (range 688-1007). All essential public health operations were provided and could be clustered in an operational or policy profile. The operational profile prevailed in all regions. Regional differences in the number of children per YHC professional were unrelated to the indicators of YHC need. The essential public health operations provided by the YHC workforce and the regional variations in children per YHC professional were not in line with indicators of YHC needs, indicating room for improvement of YHC workforce planning. The methodology applied in this study is probably relevant for use in other countries. PMID- 26358248 TI - Testicular Cancer Awareness and Knowledge: Is It the Same? Exploratory Study in a Mixed-Gender Population. AB - Testicular cancer (TC) is among the most common malignancies in the young male. Awareness plays an important role, because delay in diagnosis affects outcome. Testicular self-examination (TSE) is controversial, but recent evidence shows some cost benefits in performing this exam versus a late-stage diagnosis. The aims of this study are to determine and compare awareness for TC and TSE in males and females with the actual knowledge to this disease in an academic population. An exploratory study using an online questionnaire about TC and TSE was performed in a public university. Answers were collected and submitted to statistical analysis. A total of 815 participants-507 males (62.2 %) and 308 females (37.7 %) answered the survey. The participants that responded that they were aware of TC were 399/507 (78.7 %) males and 275/308 (89.3 %) females. About half (48.9 %) of male and 42.2 % of female respondents did not answered correctly to most common symptom, and only 15 % of males and 25 % of females answered to the question on age at diagnosis. Both gender subjects rated TSE as very important, and the majority of females were motivated to advise male partners or friends to perform TSE. This study reported a good awareness on TC and TSE, but comparing to the correct knowledge about this disease, results are disappointing. The actual knowledge about TC is low and comparable in men and women. Women revealed a better understanding of this disease and importance of TSE, suggesting that they can assume an important role in promoting health behaviors in men. PMID- 26358247 TI - Frontotemporal dementia caused by CHMP2B mutation is characterised by neuronal lysosomal storage pathology. AB - Mutations in the charged multivesicular body protein 2B (CHMP2B) cause frontotemporal dementia (FTD). We report that mice which express FTD-causative mutant CHMP2B at physiological levels develop a novel lysosomal storage pathology characterised by large neuronal autofluorescent aggregates. The aggregates are an early and progressive pathology that occur at 3 months of age and increase in both size and number over time. These autofluorescent aggregates are not observed in mice expressing wild-type CHMP2B, or in non-transgenic controls, indicating that they are a specific pathology caused by mutant CHMP2B. Ultrastructural analysis and immuno- gold labelling confirmed that they are derived from the endolysosomal system. Consistent with these findings, CHMP2B mutation patient brains contain morphologically similar autofluorescent aggregates. These aggregates occur significantly more frequently in human CHMP2B mutation brain than in neurodegenerative disease or age-matched control brains. These data suggest that lysosomal storage pathology is the major neuronal pathology in FTD caused by CHMP2B mutation. Recent evidence suggests that two other genes associated with FTD, GRN and TMEM106B are important for lysosomal function. Our identification of lysosomal storage pathology in FTD caused by CHMP2B mutation now provides evidence that endolysosomal dysfunction is a major degenerative pathway in FTD. PMID- 26358249 TI - [In Process Citation]. PMID- 26358250 TI - Human resources for primary health care in sub-Saharan Africa: progress or stagnation? AB - BACKGROUND: The World Health Organization defines a "critical shortage" of health workers as being fewer than 2.28 health workers per 1000 population and failing to attain 80% coverage for deliveries by skilled birth attendants. We aimed to quantify the number of health workers in five African countries and the proportion of these currently working in primary health care facilities, to compare this to estimates of numbers needed and to assess how the situation has changed in recent years. METHODS: This study is a review of published and unpublished "grey" literature on human resources for health in five disparate countries: Mali, Sudan, Uganda, Botswana and South Africa. RESULTS: Health worker density has increased steadily since 2000 in South Africa and Botswana which already meet WHO targets but has not significantly increased since 2004 in Sudan, Mali and Uganda which have a critical shortage of health workers. In all five countries, a minority of doctors, nurses and midwives are working in primary health care, and shortages of qualified staff are greatest in rural areas. In Uganda, shortages are greater in primary health care settings than at higher levels. In Mali, few community health centres have a midwife or a doctor. Even South Africa has a shortage of doctors in primary health care in poorer districts. Although most countries recognize village health workers, traditional healers and traditional birth attendants, there are insufficient data on their numbers. CONCLUSION: There is an "inverse primary health care law" in the countries studied: staffing is inversely related to poverty and level of need, and health worker density is not increasing in the lowest income countries. Unless there is money to recruit and retain staff in these areas, training programmes will not improve health worker density because the trained staff will simply leave to work elsewhere. Information systems need to be improved in a way that informs policy on the health workforce. It may be possible to use existing resources more cost-effectively by involving skilled staff to supervise and support lower level health care workers who currently provide the front line of primary health care in most of Africa. PMID- 26358251 TI - Pretreatment anemia and survival in nasopharyngeal carcinoma. AB - Due to the low incidence of pretreatment anemia in nasopharyngeal carcinoma (NPC), the true prognostic impact of pretreatment anemia may be underestimated before. We retrospectively analyzed the association of pretreatment anemia with disease-specific survival (DSS), distant-metastasis-free survival (DMFS), and locoregional-relapse-free survival (LRFS) by Cox regression in a cohort of 5830 patients, stratifying by midtreatment anemia, smoking, body mass index (BMI), etc. Pretreatment anemia was significantly associated with adverse DSS (hazard ratio (HR) = 2.15, 95 % confidence interval (CI) 1.62-2.85, P < 0.001) and DMFS (HR = 1.53, 95 % CI 1.08-2.17, P = 0.018), comparing to patients with normal hemoglobin, after adjusting for covariates. Moreover, the association with DSS remained unchanged regardless of smoking status and clinical stage, whereas it was limited in the subgroups of above 45 years, male sex, and BMI <25 kg/m(2). With restriction to midtreatment anemic patients, pretreatment anemia was still strongly correlated with inferior DSS and DMFS. This study, in the largest reported cohort, is the first to show the adverse prognostic impact of pretreatment anemia on DSS and DMFS in NPC. PMID- 26358252 TI - Association of genetic polymorphisms of interleukins with gastric cancer and precancerous gastric lesions in a high-risk Chinese population. AB - Helicobacter pylori (H. pylori) infection and cytokine-mediated inflammatory responses play important roles in gastric cancer (GC) pathogenesis. To investigate an association between genetic polymorphisms in interleukin (IL) 1beta, IL-4R, IL-8, IL-10, IL-16, IL-18RAP, IL-22, and IL-32 and risks of GC and its precursors, a population-based study was conducted in Linqu County. Genotypes were determined by Sequenom MassARRAY platform in 132 GC cases and 1198 subjects with gastric lesions. The H. pylori status was determined by (13)C-urea breath test ((13)C-UBT) or enzyme-linked immunosorbent assay (ELISA). Among 11 candidate single nucleotide polymorphisms (SNPs), subjects carrying IL-18RAP rs917997 AA genotype were associated with risk of GC [adjusted odds ratio (OR) = 1.83, 95 % confidence interval (CI) 1.14-2.92] or chronic atrophic gastritis (CAG; OR = 1.55, 95 % CI 1.07-2.24). The risk of GC was also increased in subjects carrying IL-32 rs2015620 A allele (AA + AT; OR = 1.92, 95 % CI 1.09-3.39). Moreover, elevated risks of CAG (OR = 2.64, 95 % CI 1.89-3.69), intestinal metaplasia (IM; OR = 5.58, 95 % CI 3.86-8.05), and dysplasia (DYS; OR = 1.64, 95 % CI 1.18-2.26) were observed in subjects with IL-22 rs1179251 CC genotype. Stratified analysis indicated that risks of GC and its precursors were elevated in subjects with IL 32 rs2015620 A allele (AA + AT) or IL-22 rs1179251 CC genotype and H. pylori infection, and significant interactions between these two SNPs and H. pylori infection were found. These findings suggested that IL-18RAP rs917997, IL-32 rs2015620, IL-22 rs1179251, and interactions between these polymorphisms and H. pylori infection were associated with risks of gastric lesions. Genetic polymorphisms of interleukins may play crucial roles in H. pylori-induced gastric carcinogenesis. PMID- 26358253 TI - BMP pathway suppression is an early event in inflammation-driven colon neoplasmatogenesis of uPA-deficient mice. AB - The suppression of the bone morphogenetic protein (BMP) signaling pathway has been recently shown to promote adenoma-to-carcinoma transition in sporadic colon cancer. However, its role in the evolution of early preneoplastic changes to neoplasia remains elusive. In the present study, we aimed to investigate the gene expression levels of multiple extracellular BMP family constituents, including BMP ligands/receptors and inhibitors, during the early stages of inflammation associated colon carcinogenesis. For that, we used the recently developed urokinase-type plasminogen activator (uPA)-deficient mouse model of colonic polypoidogenesis, in which adenomatous polyps arise several months after the induction of dextran sodium sulfate (DSS) colitis. In DSS-treated wild-type mice, the preneoplastic lesions which did not eventually evolve to adenomas resided in a colitic microenvironment characterized by a balanced upregulation of both BMP ligands, i.e., Bmp4/7 and BMP inhibitors, such as chordin, noggin, and gremlin-1. In the uPA-deficient tumor-promoting inflammatory microenvironment, however, there was a clear evidence for BMP pathway suppression. By contrast to DSS treated wild-type controls, the inflammation-associated Bmp4 upregulation was abolished, and the BMP signaling suppression was further enhanced by a particularly high increase of gremlin-1 expression. These findings propose that BMP pathway suppression in colon cancer could be associated with very early stages of the preneoplasia-to-neoplasia sequence of events. PMID- 26358254 TI - MicroRNA-related single-nucleotide polymorphism of XPO5 is strongly correlated with the prognosis and chemotherapy response in advanced non-small-cell lung cancer patients. AB - This study was performed to investigate if the microRNA-related single-nucleotide polymorphisms (miR-SNPs) of XPO5 gene predicted the prognosis and pathological features of advanced non-small-cell lung cancer patients receiving chemotherapy. A total of 131 advanced non-small-cell lung cancer (NSCLC) patients were recruited. MicroRNA (miRNA) binding site prediction software was adopted for the prediction and screening of SNPs in XPO5 and miRNA binding regions. Polymerase chain reaction (PCR) amplification was further performed. Time-dependent survival free curves were constructed using the Kaplan-Meier technique. Univariate and the multivariate survival analyses were conducted for confirmation of prognostic factor for advanced NSCLC patients receiving chemotherapy. There were no significant differences of SNP distribution frequencies between groups, without statistical significance (P > 0.05). Included clinical pathological features and chemotherapy regimens showed no apparent statistical significance in influencing the curative effect of chemotherapy in advanced NSCLC patients (all P > 0.05). While the objective response rate (ORR) in patients who carried AA and AC genotype was 35.48 and 51.22 %, respectively, with statistically significant difference (P < 0.05). Univariate survival analysis indicated that patients who carried AA genotype showed a significantly lower 5-year survival rate to those who carried AC genotype (P < 0.05). And, considering pathological features, statistical significance was found in patients with different pathological types, lymph node metastasis, differentiation degree, T staging, and pathological staging (all P < 0.05). Multivariate analysis results indicated that the SNP sites of rs11077 might be an independent prognostic factor of advanced NSCLC patients receiving chemotherapy (risk ratio [RR] = 0.346; 95 % confidence interval [95 % CI] = 0.174-0.685, P = 0.002). Other clinical features were all considered to have no apparent effect in influencing the prognostic outcomes of advanced NSCLC patients receiving chemotherapy except lymph node metastasis (P < 0.05). miR-SNP rs11077 of XPO5 may be independently connected with the prognosis and chemotherapy response of advanced NSCLC patients, and patients with AC genotype have relatively improved prognostic outcomes and better curative effect of chemotherapy than those with AA allele of XPO5. Further, lymph node metastasis may be also involved in influencing the prognosis of advanced NSCLC patients. PMID- 26358255 TI - Secreted protein acidic and rich in cysteine enhances the chemosensitivity of pancreatic cancer cells to gemcitabine. AB - It has been previously shown that the simultaneous exposure of colon cancer cells MIP to irinotecan and secreted protein acidic and rich in cysteine (SPARC) enhances anticancer activity. However, whether there is same effect of SPARC in pancreatic cancer remains largely unknown. Therefore in this study, we aimed to investigate the role of SPARC played in the sensitivity of pancreatic cancer to gemcitabine. We first treated MIAPaCa2 and MIAPaCa2/SPARC69 cells with different concentrations of gemcitabine (2, 5, 10, and 20 MUM) for 24, 48, and 72 h and selected the appropriated concentration for further study. Then we analyzed cell viability, cell cycle, and apoptosis and the levels of apoptosis-related proteins by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, fluorescence activated cell sorting and Western blot were used, respectively. In this study, we found that gemcitabine inhibited the proliferation of pancreatic cancer cells in a time- and dose-dependent manner. Overexpression of SPARC increased the inhibiting effect of gemcitabine on pancreatic cancer cells. The colony size of MIAPaCa2/SPARC69 was much smaller than that of MIAPaCa2/V. There was a G0/G1 arrest with significant increase of apoptosis after gemcitabine treatment in MIAPaCa2/SPARC69 cells. Furthermore, our results demonstrated that overexpression of SPARC markedly increased the levels of pro-apoptotic proteins in gemcitabine treated pancreatic cancer cells. The SPARC can enhance the chemosensitivity of pancreatic cancer cells to gemcitabine via regulating the expression of apoptosis related proteins. These results have shown that the SPARC/ gemcitabine combination treatment may be a potentially useful therapeutic option for individuals diagnosed with pancreatic cancer. PMID- 26358256 TI - Effect of transporter and DNA repair gene polymorphisms to lung cancer chemotherapy toxicity. AB - Lung cancer is the first leading cause of cancer deaths. Chemotherapy toxicity is one of factors that limited the efficacy of platinum-based chemotherapy in lung cancer patients. Transporters and DNA repair genes play critical roles in occurrence of platinum-based chemotherapy toxicity. To investigate the relationships between transporter and DNA repair gene polymorphisms and platinum based chemotherapy toxicity in lung cancer patients, we selected 60 polymorphisms in 14 transporters and DNA repair genes. The polymorphisms were genotyped in 317 lung cancer patients by Sequenom MassARRAY. Logistic regression was performed to estimate the association of toxicity outcome with the polymorphisms by PLINK. Our results showed that polymorphisms of SLC2A1 (rs3738514, rs4658, rs841844) were significantly related to overall toxicity. XRCC5 (rs1051685, rs6941) and AQP2 (10875989, rs3759125) polymorphisms were associated with hematologic toxicity. AQP2 polymorphisms (rs461872, rs7305534) were correlated with gastrointestinal toxicity. In conclusion, genotypes of these genes may be used to predict the platinum-based chemotherapy toxicity in lung cancer patients. PMID- 26358257 TI - Radiological and clinical assessment of the distraction achieved with remotely expandable growing rods in early onset scoliosis. AB - PURPOSES: Magnetically controlled growing rods (MCGR) allow controlled distraction of the immature spine for the treatment of early onset scoliosis. This study's primary aim was to determine the disparity between 'true' (TD) and 'intended' (ID) distraction. The secondary aim was to assess truncal growth and development during sequential lengthening. METHODS: Twenty-one patients with a maximum follow up of 37 months were included in the study. Patients in the study underwent three monthly distractions. The amount of TD was determined by measuring the expansion gap on dedicated fluoroscopic images of the actuator. The total TD to date was compared to the ID measurement reported on the external adjustment device (EAD). Weight, sitting and standing heights were recorded at each distraction. RESULTS: The average number of three monthly distractions was 8. The true to intended distraction ratio was calculated as 0.33. Patients who had undergone previous surgery gained less distraction with a ratio of 0.30 compared to patients undergoing MCGR as a primary procedure with a ratio of 0.35. Weight, sitting and standing heights increased in all patients by an average of 3.1 kg, 2.3 and 5.2 cm per year. The Cobb angle following surgical correction was maintained in 19 of 21 patients at the latest follow-up. CONCLUSIONS: The TI ratio of 0.33 suggests that for every unit of distraction registered on the EAD approximately 33 % of true distraction occurs in vivo. Increases in sitting and standing heights were observed in all patients in the study. PMID- 26358258 TI - Erratum to: Parsing Physiological Functions of Erythropoietin One Domain at a Time. PMID- 26358259 TI - Characteristics and Outcomes of Patients With Severe Bioprosthetic Aortic Valve Stenosis Undergoing Redo Surgical Aortic Valve Replacement. AB - BACKGROUND: With improved event-free survival of patients undergoing primary bioprosthetic aortic valve replacement (AVR), reoperation to relieve severe prosthetic aortic stenosis (PAS) is increasing. We sought to (1) identify of the characteristics of patients with severe bioprosthetic PAS undergoing redo AVR, and (2) assess the outcomes of these patients, along with factors associated with adverse outcomes. METHODS AND RESULTS: We studied 276 patients with severe bioprosthetic PAS (64+/-16 years, 58% men) who underwent redo-AVR between 2000 and 2012 (excluding mechanical PAS, severe other valve disease, and transcatheter AVR). Society of Thoracic Surgeons score was calculated. Severe PAS was defined as AV area <0.8 cm(2), mean AV gradient >=40 mm Hg, or dimensionless index <0.25. A composite outcome of death and congestive heart failure admission was recorded. Mean Society of Thoracic Surgeons score and mean AV gradients were 8+/-8 and 53+/ 17 mm Hg, whereas 28% had >II+ aortic regurgitation. Only 39% had an isolated redo AVR, the rest were combination surgeries (coronary bypass and/or aortic surgeries). At 4.2+/-3 years, 64 (23%) patients met the composite end point (48 deaths and 19 congestive heart failure admissions, 2.5% 30-day deaths). On multivariable Cox survival analysis, higher Society of Thoracic Surgeons score (hazard ratio, 1.35), higher grades of aortic regurgitation (hazard ratio, 1.29), and higher right ventricular systolic pressure (hazard ratio, 1.3) were associated with worse longer-term outcomes (all P<0.01). CONCLUSIONS: At an experienced center, in patients with severe bioprosthetic PAS undergoing redo AVR, the majority undergo combination surgeries but have excellent outcomes. PMID- 26358260 TI - Targeting Interleukin-1beta Reduces Leukocyte Production After Acute Myocardial Infarction. AB - BACKGROUND: Myocardial infarction (MI) is an ischemic wound that recruits millions of leukocytes. MI-associated blood leukocytosis correlates inversely with patient survival, yet the signals driving heightened leukocyte production after MI remain incompletely understood. METHODS AND RESULTS: With the use of parabiosis surgery, this study shows that soluble danger signals, among them interleukin-1beta, increase bone marrow hematopoietic stem cell proliferation after MI. Data obtained in bone marrow reconstitution experiments reveal that interleukin-1beta enhances hematopoietic stem cell proliferation by both direct actions on hematopoietic cells and through modulation of the bone marrow's hematopoietic microenvironment. An antibody that neutralizes interleukin-1beta suppresses these effects. Anti-interleukin-1beta treatment dampens the post-MI increase in hematopoietic stem cell proliferation. Consequently, decreased leukocyte numbers in the blood and infarct reduce inflammation and diminish post MI heart failure in ApoE(-/-) mice with atherosclerosis. CONCLUSIONS: The presented insight into post-MI bone marrow activation identifies a mechanistic target for muting inflammation in the ischemically damaged heart. PMID- 26358262 TI - Moving beyond cardio-centricity in heart failure risk stratification. PMID- 26358261 TI - Depression and human immunodeficiency virus infection are risk factors for incident heart failure among veterans: Veterans Aging Cohort Study. AB - BACKGROUND: Both HIV and depression are associated with increased heart failure (HF) risk. Depression, a common comorbidity, may further increase the risk of HF among adults with HIV infection (HIV+). We assessed the association between HIV, depression, and incident HF. METHODS AND RESULTS: Veterans Aging Cohort Study (VACS) participants free from cardiovascular disease at baseline (n=81 427: 26 908 HIV+, 54 519 without HIV [HIV-]) were categorized into 4 groups: HIV- without major depressive disorder (MDD) [reference], HIV- with MDD, HIV+ without MDD, and HIV+ with MDD. International Classification of Diseases, Ninth Revision codes from medical records were used to determine MDD and the primary outcome, HF. After 5.8 years of follow-up, HF rates per 1000 person-years were highest among HIV+ participants with MDD (9.32; 95% confidence interval [CI], 8.20-10.6). In Cox proportional hazards models, HIV+ participants with MDD had a significantly higher risk of HF (adjusted hazard ratio, 1.68; 95% CI, 1.45-1.95) compared with HIV- participants without MDD. MDD was associated with HF in separate fully adjusted models for HIV- and HIV+ participants (adjusted hazard ratio, 1.21; 95% CI, 1.06-1.37; and adjusted hazard ratio, 1.29; 95% CI, 1.11-1.51, respectively). Among those with MDD, baseline antidepressant use was associated with lower risk of incident HF events (adjusted hazard ratio, 0.76; 95% CI, 0.58-0.99). CONCLUSIONS: Our study is the first to suggest that MDD is an independent risk factor for HF in HIV+ adults. These results reinforce the importance of identifying and managing MDD among HIV+ patients. Future studies must clarify mechanisms linking HIV, MDD, antidepressants, and HF and identify interventions to reduce HF morbidity and mortality in those with both HIV and MDD. PMID- 26358263 TI - Drug safety of systemic treatments for psoriasis: results from The German Psoriasis Registry PsoBest. AB - The German Psoriasis Registry PsoBest was conducted in 2008 in order to investigate the long-term outcomes and safety of systemic treatments for moderate to-severe psoriasis. Safety analysis of antipsoriatic drugs with special focus on serious adverse events (SAE) for infections, malignancies and major cardiac events (MACE) was done. Nationwide non-interventional patient treatment registry conducted in 251 active dermatology centers. Until June 2012, n = 2444 patients [40 % female; mean age 47.3 (SD 14.1) years; mean duration of disease 18.2 (SD 14.7) years] were recruited, including n = 1791 patients (3842 patient years) with conventional systemic drugs and n = 908 (3442 patient years) with biological drugs. Mean PASI (Psoriasis Area and Severity Index) at inclusion was 14.7, mean DLQI (Dermatology Life Quality Index) 11.1, mean BMI (Body Mass Index) 28.2. The overall rate of SAE per 100 patient years were 1.3 (SD 0.9) per 100 patient years in conventional systemic and 1.5 (SD 1.2) in biologics (p > 0.5, no significant difference). The rates per 100 patient years for single severe adverse events were as follows (systemic/biologics): serious infections, 0.33/0.65 [CI (confidence interval) 0.13-0.54/0.35-0.98]; MACE, 0.56/0.77 (CI 0.29-0.97/0.41 1.31); malignancies (except non-melanoma skin cancer), 0.46/0.49 (CI 0.22 0.84/0.21-0.97). There were no significant differences between single drugs in any of the safety parameters. The conventional systemic and biologic drugs for psoriasis show satisfying safety under routine psoriasis care in Germany with respect to infections, MACE and malignancies. PMID- 26358265 TI - Novel porcine reproductive and respiratory syndrome virus strains in the United States with deletions in untranslated regions. AB - Porcine reproductive and respiratory syndrome (PRRS) still causes major problems for the swine industry worldwide. Here, we report the detection and genomic characterization of two novel PRRS virus (PRRSV) strains from the United States with deletions in untranslated regions (UTRs). The OH155-2015 strain has two single-nucleotide deletions in the 5' UTR, whereas the OH28372-2013 strain has a 13-nt deletion in the 3' UTR. In addition, OH155-2015 and OH28372-2013 have a unique deletion and mutations in the NSP2 and N gene, respectively. Our study highlights the importance of continued monitoring of PRRSV using whole-genome sequencing. PMID- 26358264 TI - Cross-protection of Lactococcus lactis-displayed HA2 subunit against homologous and heterologous influenza A viruses in mice. AB - Current influenza vaccines provide strain-specific protection against homologous subtypes and need to be updated annually. Therefore, it is essential to develop a universal vaccine that would induce broadly cross-protective immunity against homologous and heterologous influenza A viruses. The highly conserved HA2 subunit is a promising candidate for developing a universal influenza vaccine. Here, we hypothesized that the HA2 subunit could be displayed on the surface of Lactococcus lactis (L. lactis), using Spax as an anchor protein (L. lactis/pNZ8008-Spax-HA2) and that L. lactis/pNZ8008-Spax-HA2 would have immunogenicity by oral administration without the use of adjuvant in the mouse model. To address this hypothesis, we show that oral vaccination of mice with L. lactis/pNZ8008-Spax-HA2 elicited significant humoral and mucosal immune responses. Importantly, L. lactis/pNZ8008-Spax-HA2 provided 100% protection against homologous H5N1 or heterologous H1N1 virus challenge. These results suggest that an HA2 subunit presented on the surface of L. lactis is an effective universal vaccine candidate against influenza A viruses in the poultry industry and in humans. PMID- 26358267 TI - Letter to the Editor regarding "Reducing neck incision length during thyroid surgery does not improve satisfaction in patients" by Kim et al. PMID- 26358266 TI - Association of Erythropoietin Dose and Route of Administration with Clinical Outcomes for Patients on Hemodialysis in the United States. AB - BACKGROUND AND OBJECTIVES: Recombinant human erythropoietin (epoetin) is used routinely to increase blood hemoglobin levels in patients with ESRD and anemia. Although lower doses of epoetin are required to achieve equivalent hemoglobin responses when administered subcutaneously rather than intravenously, standard practice has been to administer epoetin to patients on hemodialysis intravenously. Randomized trials of alternative epoetin treatment regimens in patients with kidney failure have shown that risks of cardiovascular complications and death are related to the dose levels of epoetin used. Therefore, given the dose-sparing advantages of subcutaneous epoetin administration, the possibility that treatment of patients on hemodialysis with subcutaneous epoetin might be associated with more favorable outcomes compared with intravenous treatment was investigated. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A retrospective cohort study of 62,710 adult patients on hemodialysis treated with either intravenous or subcutaneous epoetin-alpha and enrolled in the Centers for Medicare and Medicaid Services ESRD Clinical Performance Measures Project from 1997 to 2005 was carried out. Risks of death and/or hospitalization for cardiovascular complications (adverse composite event outcomes) during 2 years of follow-up were determined in relationship to epoetin dose and route of administration (intravenous versus subcutaneous) by multivariate Cox proportional hazard modeling adjusted for demographics and clinical parameters. RESULTS: Epoetin doses used to achieve equivalent hemoglobin responses in study patients were, on average, 25% higher when epoetin was administered intravenously rather than subcutaneously (as expected). Moreover, adverse composite event outcomes were found to be significantly more likely to occur during follow-up for patients on hemodialysis managed with intravenous rather than subcutaneous epoetin (adjusted hazard ratio for adverse events within 1 year [intravenous versus subcutaneous] was 1.11 [95% confidence interval, 1.04 to 1.18]). CONCLUSIONS: This study finds that treatment of patients on hemodialysis with subcutaneous epoetin is associated with more favorable clinical outcomes than those associated with intravenous epoetin treatment. PMID- 26358268 TI - Vasoactive intestinal peptide reduces the inflammatory profile in mice infected with Trypanosoma cruzi. AB - Vasoactive intestinal peptide (VIP) has gained great prominence because of its therapeutic potential, which is ascribed to its ability to regulate innate immunity, inhibit antigen-specific Th1 cell responses, and generate T regulatory cells. Additionally, VIP may act as a natural antimicrobial peptide, killing bacteria, fungi, and infective forms of Trypanosoma brucei. Despite the possible relevance of VIP during the course of Chagas disease, studies regarding this in human and experimental Trypanosoma cruzi infections remain poorly characterized. In this work, we evaluated the effects of VIP on systemic and cardiac immune responses during experimental acute infection. C57BL/6 mice were infected with 5000 trypomastigotes of the VL-10 strain of T. cruzi and treated with intraperitoneal VIP injection every other day for one month. After 30 days, we observed no reduction in parasitemia levels. However, we observed a reduction in serum levels of IFN-gamma and IL-2 and an increase in that of IL-4. These data suggest that VIP treatment modified immune responses to favor the Th2 response, which had no impact on parasitemia levels although the serum level of IFN-gamma was reduced. However, this change in immune balance reduced heart damage, as noted by the smaller cardiac volume and the moderate inflammatory infiltrate observed in VIP-treated mice. Our results indicate that VIP treatment reduced the inflammatory response at the cardiac site of mice that were experimentally infected with T. cruzi. These data suggest a protective role for VIP in the heart of infected mice. PMID- 26358269 TI - Comparison of concentration methods for rapid detection of hookworm ova in wastewater matrices using quantitative PCR. AB - Hookworm infection contributes around 700 million infections worldwide especially in developing nations due to increased use of wastewater for crop production. The effective recovery of hookworm ova from wastewater matrices is difficult due to their low concentrations and heterogeneous distribution. In this study, we compared the recovery rates of (i) four rapid hookworm ova concentration methods from municipal wastewater, and (ii) two concentration methods from sludge samples. Ancylostoma caninum ova were used as surrogate for human hookworm (Ancylostoma duodenale and Necator americanus). Known concentration of A. caninum hookworm ova were seeded into wastewater (treated and raw) and sludge samples collected from two wastewater treatment plants (WWTPs) in Brisbane and Perth, Australia. The A. caninum ova were concentrated from treated and raw wastewater samples using centrifugation (Method A), hollow fiber ultrafiltration (HFUF) (Method B), filtration (Method C) and flotation (Method D) methods. For sludge samples, flotation (Method E) and direct DNA extraction (Method F) methods were used. Among the four methods tested, filtration (Method C) method was able to recover higher concentrations of A. caninum ova consistently from treated wastewater (39-50%) and raw wastewater (7.1-12%) samples collected from both WWTPs. The remaining methods (Methods A, B and D) yielded variable recovery rate ranging from 0.2 to 40% for treated and raw wastewater samples. The recovery rates for sludge samples were poor (0.02-4.7), although, Method F (direct DNA extraction) provided 1-2 orders of magnitude higher recovery rate than Method E (flotation). Based on our results it can be concluded that the recovery rates of hookworm ova from wastewater matrices, especially sludge samples, can be poor and highly variable. Therefore, choice of concentration method is vital for the sensitive detection of hookworm ova in wastewater matrices. PMID- 26358270 TI - The complete mitochondrial genomes of five Eimeria species infecting domestic rabbits. AB - Rabbit coccidiosis caused by members of the genus Eimeria can cause enormous economic impact worldwide, but the genetics, epidemiology and biology of these parasites remain poorly understood. In the present study, we sequenced and annotated the complete mitochondrial (mt) genomes of five Eimeria species that commonly infect the domestic rabbits. The complete mt genomes of Eimeria intestinalis, Eimeria flavescens, Eimeria media, Eimeria vejdovskyi and Eimeria irresidua were 6261bp, 6258bp, 6168bp, 6254bp, 6259bp in length, respectively. All of the mt genomes consist of 3 genes for proteins (cytb, cox1, and cox3), 14 gene fragments for the large subunit (LSU) rRNA and 11 gene fragments for the small subunit (SSU) rRNA, but no transfer RNA (tRNA) genes. The gene order of the mt genomes is similar to that of Plasmodium, but distinct from Haemosporida and Theileria. Phylogenetic analyses based on full nucleotide sequences using Bayesian analysis revealed that the monophyly of the Eimeria of rabbits was strongly statistically supported with a Bayesian posterior probabilities. These data provide novel mtDNA markers for studying the population genetics and molecular epidemiology of the Eimeria species, and should have implications for the molecular diagnosis, prevention and control of coccidiosis in rabbits. PMID- 26358271 TI - Juglone induces cell death of Acanthamoeba through increased production of reactive oxygen species. AB - Juglone (5-hydroxy-1,4-naphthoquinone) is a major chemical constituent of Juglans mandshruica Maxim. Recent studies have demonstrated that juglone exhibits anti cancer, anti-bacterial, anti-viral, and anti-parasitic properties. However, its effect against Acanthamoeba has not been defined yet. The aim of this study was to investigate the effect of juglone on Acanthamoeba. We demonstrate that juglone significantly inhibits the growth of Acanthamoeba castellanii at 3-5 MUM concentrations. Juglone increased the production of reactive oxygen species (ROS) and caused cell death of A. castellanii. Inhibition of ROS by antioxidant N acetyl-l-cysteine (NAC) restored the cell viability. Furthermore, our results show that juglone increased the uptake of mitochondrial specific dye. Collectively, these results indicate that ROS played a significant role in the juglone-induced cell death of Acanthamoeba. PMID- 26358272 TI - Response to the letter to the editor entitled "Forty-two-month outcome of intravitreal bevacizumab in myopic choroidal neovascularization". PMID- 26358274 TI - Surgical methods for tubal pregnancy - effects on ovarian response to controlled stimulation during IVF. AB - INTRODUCTION: Tubal pregnancy is often treated by surgery: salpingotomy or salpingectomy. Concern has been raised regarding the risk of compromising the vascular and nervous supply to the ovary, following salpingectomy. The aim of this study was to investigate whether the ovarian response to controlled ovarian stimulation for in vitro fertilization (IVF) is reduced after salpingectomy in comparison with salpingotomy, among women undergoing IVF subsequent to surgical treatment of tubal pregnancy. MATERIAL AND METHODS: This retrospective cohort study included 153 women who had undergone IVF after surgery for ectopic tubal pregnancy. Women treated by either salpingectomy or salpingotomy constituted the two groups. Potential confounders (age, body mass index, smoking, stimulation dosage of gonadotrophin and reason for IVF) were included in multivariable regression analyses. The primary outcome was number of retrieved oocytes. The secondary outcomes were clinical pregnancy and live birth rates. RESULTS: A total of 118 women had undergone unilateral salpingectomy and 35 women had undergone unilateral salpingotomy. The mean number of oocytes at aspiration in the subsequent IVF cycle was 11.8 (salpingectomy group) and 11.7 (salpingotomy group). A linear regression analysis showed no effect of treatment type on aspirated oocytes [beta = -0.11, 95% confidence interval -2.27, 2.04 (p = 0.92)]. Adjustment for potential confounders did not alter the result. CONCLUSION: Among women undergoing IVF after surgery for tubal pregnancy, the ovarian response was not influenced by the surgical method. Our results do not support the theory that salpingectomy, compared with salpingotomy, impairs ovarian reserve measured as number of oocytes retrieved during subsequent IVF treatment. PMID- 26358273 TI - S100A4 gene silencing in oxygen-induced ischemic retinopathy inhibits retinal neovascularization via down-regulation of CREB expression. AB - PURPOSE: To investigate the possible role of S100A4 in retinal neovascularization (RNV), as well as the underlying mechanism, in a mouse model of oxygen-induced retinopathy (OIR). METHODS: Retinas used in the experiments were obtained from a mouse model of OIR with and without treatment by intravitreal injection of adnoviral-S100A4-RNAi or adenoviral-green fluorescent protein at postnatal day 12 (P12). At P17, the efficacy of adenoviral gene transfer was assessed with fluorescence microscopy. RNV was evaluated by whole-mount immunofluorescent staining of the mouse retina with Griffonia simplicifolia isolectin B4 conjugated to Alexa Fluor 594 and quantified by counting the number of pre-retinal neovascular cells. Protein and mRNA expression levels of S100A4, cyclic AMP (cAMP) response element-binding protein (CREB), B-cell lymphoma 2 (Bcl-2), and caspase-3 were determined using Western blot analysis and real-time PCR. RESULTS: Retinal S100A4 levels were positively correlated with the progression of RNV. In the intravitreal Ad-S100A4-RNAi transfer mice, both S100A4 protein and mRNA expression levels in the retina were significantly decreased at P17. Ad-S100A4 RNAi transfer was clearly demonstrated by the green fluorescent protein (GFP) in many layers of the retina, including the ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), and outer nuclear layer (ONL), 3 days after intravitreal injection. Whole-mount immunofluorescent staining of the retina and quantification of the pre-retinal neovascular cells demonstrated that RNV was significantly ameliorated. At the same time, the expression of CREB and Bcl-2 were significantly decreased at the transcriptional and translational levels in the OIR-S100A4 group, whereas caspase 3 expression was increased. CONCLUSIONS: Our results indicated that RNV was ameliorated by Ad-S100A4-RNAi transfer in a mouse model of OIR through mediation of the anti-apoptotic effect of Bcl-2 by reducing the expression of CREB, and that S100A4 may be a novel therapeutic target for ocular neovascularization diseases. PMID- 26358275 TI - Monitoring of Levamisole Concentration in Serum of Traffic Participants after Cocaine Consumption. AB - This study highlights the problem of levamisole-adulterated cocaine in context of active traffic participation. For the purposes of levamisole concentration monitoring in human serum, an analytical method based on LC-MS/MS and solid-phase extraction was applied. A Luna 5 MUm C18 (2) 100 A, 150 mm * 2 mm column and a mobile phase consisting of A (H2 O/methanol = 95/5, v/v) and B (H2 O/methanol = 3/97, v/v), both with 10 mM ammonium acetate and with 0.1% acetic acid (pH = 3.2), were used. The validation experiments demonstrated that the method applied was appropriate for levamisole quantification in human serum. For 23% of levamisole-positive samples, the concentrations exceeded 20 ng/mL. Therefore, the interaction of this drug with cocaine has to be considered as important for active traffic participation. As a consequence, monitoring of levamisole concentration in human serum is recommended, as long as it is used as cocaine adulterant. PMID- 26358276 TI - Liver Transplantation to the Active Smoker: Transplant Provider Opinions and How They Have Changed : Transplantation in Smokers: A Survey. AB - Awareness of smoking complications in liver transplantation patients is increasing. No study in the past 15 years has addressed attitudes toward offering transplantation to smokers. Our aim was to determine smoking policies nationwide. We conducted a survey of liver transplantation centers. The seven-question survey was sent to medical and surgical directors of liver transplantation. Results were analyzed in R 3.1.1 using two-tailed t testing and ANOVA. Fifty one of 110 centers (46 %) responded. Volume transplanted annually ranged from 10 to 190. Most respondents acknowledged a policy on smoking (38/51, 75 %). Most centers with policies required cessation (32/38, 84 %). All other centers did encourage attempts at cessation (19/19, 100 %). Whether smoking cessation was required differed by region (p = 0.02). Southern programs more commonly required smoking cessation (87.5 vs. 38.4 %, p < 0.001). The highest rates of smoking cessation were noted in the Southwest (90.0 %) and the lowest in the Northeast (26.2 %). There was a trend toward requiring cessation in larger-volume centers. Most respondents had a tobacco policy and tended to require abstinence; however, ultimately centers were divided on requiring cessation. Regional differences were noted, with the South more commonly requiring cessation. Our results indicate lack of consensus among transplantation centers regarding access of smokers to liver transplantation. PMID- 26358277 TI - Starting a High-Quality Pancreatic Surgery Program at a Community Hospital. AB - BACKGROUND: Most literature suggests that pancreatic resections should be done by high-volume surgeons at high-volume hospitals to optimize patient outcomes. However, patient preference and insurance requirements may restrict hospital location. After careful planning, a high-volume pancreatic surgeon started performing pancreatectomies at a community hospital. METHODS: Sixty pancreatectomies were performed at an academic medical center and 28 at a 144-bed community, non-teaching hospital. Sixty-day outcomes were recorded. RESULTS: There were no statistically significant differences between the academic medical center and community hospital with regard to the median age of the patients (66 vs. 61 years), the gender distribution (57 vs. 64 % female), or the median BMI (28 vs. 26 kg/m(2)). There was a significant difference in the American Society of Anesthesiologists class distribution between the academic medical center and community hospital (1; 0 vs. 4 %, 2; 7 vs. 21 %, 3; 88 vs. 75 %, 4; 5 vs. 0 %, p = 0.006). The median length of stay (LOS) for 17 pancreaticoduodenectomy/total pancreatectomy patients at the community hospital was significantly less than for 39 patients at the academic medical center (5 vs. 7 days, p = 0.006). Eleven distal pancreatectomy/splenectomy patients at the community hospital tended to have a shorter median LOS than 21 patients at the academic medical center (4 vs. 5 days, p = 0.25). Accordion >= 3 complications (7 vs. 27 %) and readmissions (11 vs. 22 %) tended to be lower at the community hospital than the academic medical center. Greater than 80 % of patients with adenocarcinoma at both hospital settings who were recommended to receive adjuvant therapy started their treatment within 60 days of surgery. CONCLUSIONS: With appropriate planning and careful patient selection, high-quality pancreatic surgery can be performed at a community hospital by a high-volume pancreatic surgeon. PMID- 26358278 TI - Is It Reasonable to Treat Early Gastric Cancer with Mucosal Infiltration and Well Differentiation by Endoscopic Submucosal Resection? AB - BACKGROUND: While limited endoscopic submucosal dissection (ESD) is increasingly applied in the treatment of early gastric cancer, preoperative prediction of lymph node metastasis is very critical for determining treatment strategies preoperatively. Thus, the aim of this study was to accurately assess the prevalence and pattern of lymph node metastasis in early gastric cancer patients and to identify the best candidates for ESD. METHODS: From September 2008 to December 2013, a total of 539 patients with early gastric cancer were retrospectively analyzed in the present study. Of them, 503 patients underwent radical gastrectomy and 36 patients underwent ESD. The clinicopathological features were collected and correlations with lymph node metastasis were analyzed. The survival rates of patients were also analyzed. RESULTS: Lymph node metastasis was observed in 80 of 503 patients (15.9 %). Among these, the rate for mucosal cancer was 8.3 %, and 20.1 % for submucosal cancer. By univariate analysis, risk factors for lymph node metastasis were growth pattern, tumor size, pathological type, depth of invasion, lymphatic-vascular invasion, and neural invasion. By multivariate analysis, risk factors for lymph node metastasis were tumor size, pathological type, depth of invasion, and lymphatic-vascular invasion. The incidence of lymph node metastasis was 0 % in the well differentiated mucosal cancers, irrespective of tumor size. For the well differentiated mucosal cancers, the overall survival rates were comparable between patients underwent gastrectomy with lymph node dissection and patients underwent ESD (100 vs 100 %). CONCLUSIONS: The most important factors for predicting lymph node metastasis in early gastric cancer are tumor size, pathological type, depth of invasion, and lymphatic-vascular invasion. Well differentiated mucosal gastric cancers could be candidates for ESD. PMID- 26358279 TI - Kinase hinge binding scaffolds and their hydrogen bond patterns. AB - Protein kinases constitute a major class of intracellular signaling molecules, and describe some of the most prominent drug targets. Kinase inhibitors commonly employ small chemical scaffolds that form hydrogen bonds with the kinase hinge residues connecting the N- and C-terminal lobes of the catalytic domain. In general the satisfied hydrogen bonds are required for potent inhibition, therefore constituting a conserved feature in the majority of inhibitor-kinase interactions. From systematically analyzing the kinase scaffolds extracted from Pfizer crystal structure database (CSDb) we recognize that large number of kinase inhibitors of diverse chemical structures are derived from a relatively small number of common scaffolds. Depending on specific substitution patterns, scaffolds may demonstrate versatile binding capacities to interact with kinase hinge. Afforded by thousands of ligand-protein binary complexes, the hinge hydrogen bond patterns were analyzed with a focus on their three-dimensional configurations. Most of the compounds engage H6 NH for hinge recognition. Dual hydrogen bonds are commonly observed with additional recruitment of H4 CO upstream and/or H6 CO downstream. Triple hydrogen bonds accounts for small number of binary complexes. An unusual hydrogen bond with a non-canonical H5 conformation is observed, requiring a peptide bond flip by a glycine residue at the H6 position. Additional hydrogen bonds to kinase hinge do not necessarily correlate with an increase in potency; conversely they appear to compromise kinase selectivity. Such learnings could enhance the prospect of successful therapy design. PMID- 26358280 TI - Novel inhibitors targeting PPM1D phosphatase potently suppress cancer cell proliferation. AB - Protein phosphatase magnesium-dependent 1delta (PPM1D, Wip1) is a p53 inducible serine/threonine phosphatase. PPM1D is a promising target protein in cancer therapy since overexpression, missense mutations, truncating mutations, and gene amplification of PPM1D are reported in many tumors, including breast cancer and neuroblastoma. Herein, we report that a specific inhibitor, SL-176 that can be readily synthesized in 10 steps, significantly inhibits proliferation of a breast cancer cell line overexpressing PPM1D and induces G2/M arrest and apoptosis. SL 176 decreases PPM1D enzyme activity potently and specifically in vitro. These results demonstrate that SL-176 could be a useful lead compound in the development of effective anti-cancer agents. PMID- 26358281 TI - Isolation and anticancer, anthelminthic, and antiviral (HIV) activity of acylphloroglucinols, and regioselective synthesis of empetrifranzinans from Hypericum roeperianum. AB - From the ethno-medicinally used leaves of Hypericum roeperianum we isolated a new tricyclic acylphloroglucinol (1), a new tetracyclic acylphloroglucinol (2), and a new prenylated bicyclic acylphloroglucinol (3) together with four known prenylated (4-7) and three known tetracyclic acylphloroglucinol derivatives (8 10). Structure elucidation was based on UV, IR, [alpha]D(25), 1D- and 2D-NMR experiments. Furthermore, empetrifranzinans A (8) and C (9) were synthesized regioselectively in only two steps. The isolated compounds were evaluated for their cytotoxicity against PC-3 and HT-29 cancer cell lines as well as antibacterial and anthelmintic activities. They were also tested in cell-based assays for cytotoxicity against MT-4 cells and for anti-HIV activity in infected MT-4 cells. Significant anthelmintic activity against Caenorhabditis elegans was exhibited by compound 7 (3-geranyl-1-(2'-methylbutanoyl)-phloroglucinol), which might provide a new lead. PMID- 26358282 TI - A real-time classification algorithm for EEG-based BCI driven by self-induced emotions. AB - BACKGROUND AND OBJECTIVE: The aim of this paper is to provide an efficient, parametric, general, and completely automatic real time classification method of electroencephalography (EEG) signals obtained from self-induced emotions. The particular characteristics of the considered low-amplitude signals (a self induced emotion produces a signal whose amplitude is about 15% of a really experienced emotion) require exploring and adapting strategies like the Wavelet Transform, the Principal Component Analysis (PCA) and the Support Vector Machine (SVM) for signal processing, analysis and classification. Moreover, the method is thought to be used in a multi-emotions based Brain Computer Interface (BCI) and, for this reason, an ad hoc shrewdness is assumed. METHOD: The peculiarity of the brain activation requires ad-hoc signal processing by wavelet decomposition, and the definition of a set of features for signal characterization in order to discriminate different self-induced emotions. The proposed method is a two stages algorithm, completely parameterized, aiming at a multi-class classification and may be considered in the framework of machine learning. The first stage, the calibration, is off-line and is devoted at the signal processing, the determination of the features and at the training of a classifier. The second stage, the real-time one, is the test on new data. The PCA theory is applied to avoid redundancy in the set of features whereas the classification of the selected features, and therefore of the signals, is obtained by the SVM. RESULTS: Some experimental tests have been conducted on EEG signals proposing a binary BCI, based on the self-induced disgust produced by remembering an unpleasant odor. Since in literature it has been shown that this emotion mainly involves the right hemisphere and in particular the T8 channel, the classification procedure is tested by using just T8, though the average accuracy is calculated and reported also for the whole set of the measured channels. CONCLUSIONS: The obtained classification results are encouraging with percentage of success that is, in the average for the whole set of the examined subjects, above 90%. An ongoing work is the application of the proposed procedure to map a large set of emotions with EEG and to establish the EEG headset with the minimal number of channels to allow the recognition of a significant range of emotions both in the field of affective computing and in the development of auxiliary communication tools for subjects affected by severe disabilities. PMID- 26358283 TI - Chronic Kidney Disease: A Place for Primary Care and Nephrology to Meet. PMID- 26358284 TI - Ethical Questions in Medical Electronic Adherence Monitoring. AB - Electronic adherence monitors (EAMs) record and report an array of health behaviors, ranging from taking daily medications to wearing medical devices. EAMs are utilized in research worldwide and are being investigated for clinical use. However, there is also growing popular concern about the extent to which electronic devices may be used to monitor individuals, including allegations in the media that EAMs represent a move towards "Big Brother" in medicine. Here, we highlight the unique benefits as well as the potential ethical challenges that electronic adherence monitoring generates. These challenges surround autonomy, privacy and confidentiality, trust, and ancillary care obligations. We describe key questions within each of these domains that warrant further investigation, and present potential solutions to many of the concerns raised. PMID- 26358285 TI - Incidence of Fractures in Patients With Type 2 Diabetes in the SAVOR-TIMI 53 Trial. AB - OBJECTIVE: Patients with type 2 diabetes have an increased risk of bone fractures, the predisposing factors for which are unknown. Treatment with thiazolidinediones (TZDs) further increases the incidence of osteoporotic fractures. In the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus-Thrombolysis in Myocardial Infarction 53 (SAVOR TIMI 53) trial, fractures were considered an adverse event of special interest, and information regarding fractures was collected. RESEARCH DESIGN AND METHODS: We compared the incidence of fractures among the 8,280 patients who were assigned to treatment with saxagliptin with that in the 8,212 patients who were assigned to placebo. We further analyzed the participants' baseline characteristics and fracture risk. RESULTS: During a median follow-up of 2.1 years, 241 patients (2.9%) in the saxagliptin group and 240 (2.9%) in the placebo group experienced a fracture (hazard ratio [HR] 1.00 [95% CI 0.83-1.19]). Event rates for fractures were the same in both treatment arms: 14.7 per 1,000 patient-years in the entire population and 14.0 in the on-treatment population (first event only). Fracture risk was similar in patients treated with saxagliptin or placebo across different subgroups defined by race, cardiovascular risk, and renal function. A multivariable Cox regression analysis showed that risk of fracture was associated with female sex (P < 0.0001), longer diabetes duration (P < 0.0001), older age (P = 0.002), major hypoglycemic events (P = 0.01), noncompliance with study drug (P = 0.01), and treatment with TZDs (P = 0.03). CONCLUSIONS: In a large population of older patients with type 2 diabetes, treatment with saxagliptin was not associated with an increased risk of fractures. The association between longer diabetes duration and increased risk of bone fracture is an intriguing finding. PMID- 26358286 TI - Duration and Degree of Weight Gain and Incident Diabetes in Younger Versus Middle Aged Black and White Adults: ARIC, CARDIA, and the Framingham Heart Study. AB - OBJECTIVE: To determine whether duration and degree of weight gain are differentially associated with diabetes risk in younger versus middle-aged black and white adults. RESEARCH DESIGN AND METHODS: We combined data from three cohort studies: Atherosclerosis Risk in Communities (ARIC), Coronary Artery Risk Development in Young Adults (CARDIA), and the Framingham Heart Study. A total of 17,404 participants (56% women; 21% black) were stratified by baseline age (younger: >=30 and <45 years; middle-aged: >=45 and <60 years) and examined for incident diabetes (median follow-up 9 years). Duration and degree of gain in BMI were calculated as "BMI-years" above one's baseline BMI. RESULTS: Diabetes incidence per 1,000 person-years in the younger and middle-aged groups was 7.2 (95% CI 5.7, 8.7) and 24.4 (22.0, 26.8) in blacks, respectively, and 3.4 (2.8, 4.0) and 10.5 (9.9, 11.2) in whites, respectively. After adjusting for sex, baseline BMI and other cardiometabolic factors, and age and race interaction terms, gains in BMI-years were associated with higher risk of diabetes in the younger compared with middle-aged groups: hazard ratios for 1-unit increase in log BMI-years in younger versus middle-aged blacks were 1.18 (P = 0.02) and 1.02 (P = 0.39), respectively (P for interaction by age-group = 0.047), and in whites were 1.35 (P < 0.001) and 1.11 (P < 0.001), respectively (P for interaction by age-group = 0.008). CONCLUSIONS: Although middle-aged adults have higher rates of diabetes, younger adults are at greater relative risk of developing diabetes for a given level of duration and degree of weight gain. PMID- 26358287 TI - Pharmacokinetics and Pharmacodynamics of NPH Insulin in Type 1 Diabetes: The Importance of Appropriate Resuspension Before Subcutaneous Injection. AB - OBJECTIVE: Crystalline NPH insulin comes in a two-phase solution with either a solvent or a rapid-acting insulin (in premixed formulations) and needs adequate mixing for complete resuspension before injection. The aim of this study was to establish pharmacokinetics (PK) and pharmacodynamics (PD) after injection of appropriately resuspended versus nonresuspended NPH insulin. RESEARCH DESIGN AND METHODS: PK and PD were assessed after subcutaneous injection of NPH insulin 0.35 units/kg at steady state by pen either resuspended (R+, tipping of insulin pen 20 times) or nonresuspended (pen maintained in fixed position either horizontally [R horizontal] or vertically with tip up [R- up] or tip down [R- down]). Eleven subjects with type 1 diabetes (age 31.5 +/- 12 years, diabetes duration 17.5 +/- 7.7 years, BMI 22.9 +/- 1.5 kg/m2, A1C 7.2 +/- 0.4% [55.2 +/- 4.4 mmol/mol]) were studied (euglycemic clamp) with a randomized crossover design. RESULTS: Compared with resuspended NPH insulin (R+), nonresuspended NPH insulin resulted in profound PK/PD differences with either reduced (R- horizontal and R- up) or increased (R- down) plasma insulin concentrations [FIRI_AUC(0-end of study) (free immunoreactive insulin area under the concentration-time curve between 0 and end of study)] and PD activity [glucose infusion rate (GIR)_AUC(0-end of study)] (all P < 0.05). Duration of NPH insulin action was shorter in R- up (9.4 +/- 1.7 h) but longer in R- down (15.4 +/- 2.3 h) compared with R+ (11.8 +/- 2.6 h) (P < 0.05). Within-subject variability (percent coefficient of variation) among studies was as high as 23% for PK [FIRI_AUC(0-end of study)] and 62% for PD [GIR_AUC(0-end of study)]. CONCLUSIONS: Compared with resuspended NPH insulin, lack of resuspension profoundly alters PK/PD and may importantly contribute to day-to-day glycemic variability of type 1 diabetes. PMID- 26358288 TI - A Phase 2, Randomized, Dose-Finding Study of the Novel Once-Weekly Human GLP-1 Analog, Semaglutide, Compared With Placebo and Open-Label Liraglutide in Patients With Type 2 Diabetes. AB - OBJECTIVE: To investigate the dose-response relationship of semaglutide versus placebo and open-label liraglutide in terms of glycemic control in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: This was a 12-week, randomized, double-blind phase 2 trial. Patients (n = 415) were randomized to receive a subcutaneous injection of semaglutide once weekly without dose escalation (0.1 0.8 mg) or with dose escalation (E) (0.4 mg steps to 0.8 or 1.6 mg E over 1-2 weeks), open-label liraglutide once daily (1.2 or 1.8 mg), or placebo. The primary end point was change in HbA1c level from baseline. Secondary end points included change in body weight, safety, and tolerability. RESULTS: Semaglutide dose-dependently reduced the level of HbA1c from baseline (8.1 +/- 0.8%) to week 12 by up to -1.7%, and body weight by up to -4.8 kg (1.6 mg E, P < 0.001 vs. placebo). Up to 81% of patients achieved an HbA1c level of <7%. HbA1c level and weight reductions with semaglutide 1.6 mg E were greater than those with liraglutide 1.2 and 1.8 mg (based on unadjusted CIs), but adverse events (AEs) and withdrawals occurred more frequently. The incidence of nausea, vomiting, and withdrawal due to gastrointestinal AEs increased with the semaglutide dose; most events were mild to moderate, transient, and ameliorated by dose escalation. There were no major episodes of hypoglycemia and few cases of injection site reactions. CONCLUSIONS: After 12 weeks, semaglutide dose-dependently reduced HbA1c level and weight in patients with type 2 diabetes. No unexpected safety or tolerability concerns were identified; gastrointestinal AEs typical of glucagon like peptide 1 receptor agonists were mitigated by dose escalation. On this basis, weekly semaglutide doses of 0.5 and 1.0 mg with a 4-week dose escalation were selected for phase 3. PMID- 26358289 TI - Immunohistochemical and radiological characterization of wound healing in porcine liver after radiofrequency ablation. AB - BACKGROUND: Radiofrequency ablation (RFA) is a minimal invasive therapeutic option for patients with hepatocellular carcinoma or liver metastases. We investigated RFA-induced cellular changes in the liver of pigs. MATERIAL AND METHODS: Healthy pigs (n=18) were sacrificed between day 0 and 3 months after RFA. The wound healing process was evaluated by computed tomography (CT), chromotrope anilinblue (CAB) staining of large-scale and standard tissue sections. Immunohistochemistry (IHC) for heat shock protein 70, Caspase-3, Ki67, Reelin, Vinculin, Vimentin and alpha-SMA was perfomed. RESULTS: One day after RFA, CAB staining showed cell damage and massive hyperaemia. All IHC markers were predominantly expressed at the outer borders of the lesion, except Reelin, which was mainly detected in untreated liver regions. By staining for Hsp70, the heat stress during RFA was monitored, which was most distinct 1-2 days after RFA. CT revealed decreased lesion size after one week. Development of a Vimentin and alpha-SMA positive fibrotic capsule was observed. CONCLUSION: In the early phase signs of cell damage, apoptosis and proliferation are dominant. Reduced expression of Reelin suggests a minor role of hepatic stellate cells in the RFA zone. After one week myofibroblasts become prominent and contribute to the development of the fibrotic capsule. This elucidates the pathophysiology of RFA and could contribute to the future optimization of RFA procedures. PMID- 26358291 TI - Structure-directed construction of a high-performance version of the enzyme FabG from the photosynthetic microorganism Synechocystis sp. PCC 6803. AB - PhaB (acetoacetyl-CoA reductase) catalyzes the reduction of acetoacetyl-CoA to (R)-3-hydroxybutyryl-CoA in polyhydroxybutyrate (PHB) synthesis and FabG (3 ketoacyl-acyl-carrier-protein reductase) catalyzes the beta-ketoacyl-ACP to yield (R)-3-hydroxyacyl-ACP in fatty acid biosynthesis. Both of them have been classified into the same group EC 1.1.1. PhaB is limited with substrate specificities, while FabG was considered as a potential PhaB due to broad substrate selectivity despite of low activity. Here, X-ray crystal structures of FabG and PhaB from the photosynthetic microorganism Synechocystis sp. PCC 6803 were resolved. Based on them, a high-performance FabG on acyl-CoA directed by structural evolution was constructed that may serve as a critical enzyme to partition carbon flow from fatty acid synthesis to PHA. PMID- 26358290 TI - Shared Ligands Between Organic Anion Transporters (OAT1 and OAT6) and Odorant Receptors. AB - The multispecific organic anion drug transporters OAT6 (SLC22A20) and OAT1 (SLC22A6) are expressed in nasal epithelial cells and both can bind odorants. Sequence analysis of OAT6 revealed an evolutionarily conserved 79-amino acid (AA) fragment present not only in OAT6 but also in other SLC22 transporters, such as the organic anion transporter (OAT), organic carnitine transporter (OCTN), and organic cation transporter (OCT) subfamilies. A similar fragment is also conserved in some odorant receptors (ORs) in both humans and rodents. This fragment is located in regions believed to be important for ligand/substrate preference and recognition in both classes of proteins, raising the possibility that it may be part of a potential common ligand/substrate recognition site in certain ORs and SLC22 transporters. In silico screening of an odorant database containing known OR ligands with a pharmacophore hypothesis (generated from a set of odorants known to bind OAT6 and/or OAT1), followed by in vitro uptake assays in transfected cells, identified OR ligands capable of inhibiting OAT6- and/or OAT1-mediated transport, albeit with different affinities. The conservation of the AA fragments between these two different classes of proteins, together with their coexpression in olfactory as well as other tissues, suggests the possibility that ORs and SLC22 transporters function in concert, and raises the question as to whether these transporters function in remote sensing and signaling and/or as transceptors. PMID- 26358292 TI - Misfolded opsin mutants display elevated beta-sheet structure. AB - Mutations in rhodopsin can cause misfolding and aggregation of the receptor, which leads to retinitis pigmentosa, a progressive retinal degenerative disease. The structure adopted by misfolded opsin mutants and the associated cell toxicity is poorly understood. Forster resonance energy transfer (FRET) and Fourier transform infrared (FTIR) microspectroscopy were utilized to probe within cells the structures formed by G188R and P23H opsins, which are misfolding mutants that cause autosomal dominant retinitis pigmentosa. Both mutants formed aggregates in the endoplasmic reticulum and exhibited altered secondary structure with elevated beta-sheet and reduced alpha-helical content. The newly formed beta-sheet structure may facilitate the aggregation of misfolded opsin mutants. The effects observed for the mutants were unrelated to retention of opsin molecules in the endoplasmic reticulum itself. PMID- 26358294 TI - Dissection and engineering of the Escherichia coli formate hydrogenlyase complex. AB - The Escherichia coli formate hydrogenlyase (FHL) complex is produced under fermentative conditions and couples formate oxidation to hydrogen production. In this work, the architecture of FHL has been probed by analysing affinity-tagged complexes from various genetic backgrounds. In a successful attempt to stabilize the complex, a strain encoding a fusion between FdhF and HycB has been engineered and characterised. Finally, site-directed mutagenesis of the hycG gene was performed, which is predicted to encode a hydrogenase subunit important for regulating sensitivity to oxygen. This work helps to define the core components of FHL and provides solutions to improving the stability of the enzyme. PMID- 26358293 TI - PKA-mediated phosphorylation of Dexras1 suppresses iron trafficking by inhibiting S-nitrosylation. AB - Dexras1 is a small GTPase and plays a central role in neuronal iron trafficking. We have shown that stimulation of glutamate receptors activates neuronal nitric oxide synthase, leading to S-nitrosylation of Dexras1 and a physiological increase in iron uptake. Here we report that Dexras1 is phosphorylated by protein kinase A (PKA) on serine 253, leading to a suppression of iron influx. These effects were directly associated with the levels of S-nitrosylated Dexras1, whereby PKA activation reduced Dexras1 S-nitrosylation in a dose dependent manner. Moreover, we found that adiponectin modulates Dexras1 via PKA. Hence these findings suggest the involvement of the PKA pathway in modulating glutamate mediated ROS in neurons, and hint to a functional crosstalk between S nitrosylation and phosphorylation. PMID- 26358295 TI - COX assembly factor ccdc56 regulates mitochondrial morphology by affecting mitochondrial recruitment of Drp1. AB - Mitochondria are dynamic organelles that alter their morphology in response to cellular signaling and differentiation through balanced fusion and fission. In this study, we found that the mitochondrial inner membrane ATPase ATAD3A interacted with ccdc56/MITRAC12/COA3, a subunit of the cytochrome oxidase (COX) assembly complex. Overproduction of ccdc56 in HeLa cells resulted in fragmented mitochondrial morphology, while mitochondria were highly elongated in ccdc56 repressed cells by the defective recruitment of the fission factor Drp1. We also found that mild and chronic inhibition of COX led to mitochondrial elongation, as seen in ccdc56-repressed cells. These results indicate that ccdc56 positively regulates mitochondrial fission via regulation of COX activity and the mitochondrial recruitment of Drp1, and thus, suggest a novel relationship between COX assembly and mitochondrial morphology. PMID- 26358296 TI - Magnetic Particle Imaging tracks the long-term fate of in vivo neural cell implants with high image contrast. AB - We demonstrate that Magnetic Particle Imaging (MPI) enables monitoring of cellular grafts with high contrast, sensitivity, and quantitativeness. MPI directly detects the intense magnetization of iron-oxide tracers using low frequency magnetic fields. MPI is safe, noninvasive and offers superb sensitivity, with great promise for clinical translation and quantitative single cell tracking. Here we report the first MPI cell tracking study, showing 200-cell detection in vitro and in vivo monitoring of human neural graft clearance over 87 days in rat brain. PMID- 26358297 TI - Genome-wide analysis of DNA methylation in pigs using reduced representation bisulfite sequencing. AB - DNA methylation plays a major role in the epigenetic regulation of gene expression. Although a few DNA methylation profiling studies of porcine genome which is one of the important biomedical models for human diseases have been reported, the available data are still limited. We tried to study methylation patterns of diverse pig tissues as a study of the International Swine Methylome Consortium to generate the swine reference methylome map to extensively evaluate the methylation profile of the pig genome at a single base resolution. We generated and analysed the DNA methylome profiles of five different tissues and a cell line originated from pig. On average, 39.85 and 62.1% of cytosine and guanine dinucleotides (CpGs) of CpG islands and 2 kb upstream of transcription start sites were covered, respectively. We detected a low rate (an average of 1.67%) of non-CpG methylation in the six samples except for the neocortex (2.3%). The observed global CpG methylation patterns of pigs indicated high similarity to other mammals including humans. The percentage of CpG methylation associated with gene features was similar among the tissues but not for a 3D4/2 cell line. Our results provide essential information for future studies of the porcine epigenome. PMID- 26358299 TI - Evaluation of intrathecal baclofen delivery system malfunction by computed tomography scan. AB - AIM: To describe the computed tomography (CT) findings encountered when catheter patency is questionable. The role of CT in directing treatment is evaluated. METHOD: Records of children with intrathecal baclofen pump management were reviewed. Only patients with CT evaluation who had revision pump/catheter surgery were included. RESULTS: From 295 patients, 27 had CT contrast study; in three of them, baclofen could not be aspirated and the procedure was stopped, eight had normal scan and did not need surgery and 16 patients were reported. Four patients had normal CT (free contrast formed a perfect crescent shape), and had surgery because the pump battery was close to expiration. Five patients had inadequate fluid pooling (fluid was seen without a crescent shape). Five patients had fluid leak (fluid was seen around the pump or in the lumbar canal below catheter entrance level or outside the canal in the lumbar region). Two patients had catheter occlusion (fluid loculation around the catheter tip with no free flow). INTERPRETATION: CT contrast study is safe and effective for locating defects in intrathecal baclofen delivery system. When catheter patency is questionable, CT plays an important role in directing the next step of management. PMID- 26358298 TI - Complete genome and gene expression analyses of Asaia bogorensis reveal unique responses to culture with mammalian cells as a potential opportunistic human pathogen. AB - Asaia bogorensis, a member of acetic acid bacteria (AAB), is an aerobic bacterium isolated from flowers and fruits, as well as an opportunistic pathogen that causes human peritonitis and bacteraemia. Here, we determined the complete genomic sequence of the As. bogorensis type strain NBRC 16594, and conducted comparative analyses of gene expression under different conditions of co-culture with mammalian cells and standard AAB culture. The genome of As. bogorensis contained 2,758 protein-coding genes within a circular chromosome of 3,198,265 bp. There were two complete operons encoding cytochrome bo3-type ubiquinol terminal oxidases: cyoABCD-1 and cyoABCD-2. The cyoABCD-1 operon was phylogenetically common to AAB genomes, whereas the cyoABCD-2 operon belonged to a lineage distinctive from the cyoABCD-1 operon. Interestingly, cyoABCD-1 was less expressed under co-culture conditions than under the AAB culture conditions, whereas the converse was true for cyoABCD-2. Asaia bogorensis shared pathogenesis related genes with another pathogenic AAB, Granulibacter bethesdensis, including a gene coding pathogen-specific large bacterial adhesin and additional genes for the inhibition of oxidation and antibiotic resistance. Expression alteration of the respiratory chain and unique hypothetical genes may be key traits that enable the bacterium to survive under the co-culture conditions. PMID- 26358300 TI - Services for people at high risk improve outcomes in patients with first episode psychosis. AB - OBJECTIVE: About one-third of patients referred to services for people at high risk for psychosis may have already developed a first episode of psychosis (FEP). We compared clinical outcomes in FEP patients who presented to either high risk or conventional mental health services. METHOD: Retrospective study comparing duration of hospital admission, referral-to-diagnosis time, need for compulsory hospital admission and frequency of admission in patients with FEP who initially presented to a high-risk service (n = 164) to patients with FEP who initially presented to conventional mental health services (n = 2779). Regression models were performed, controlling for several confounders. RESULTS: FEP patients who had presented to a high-risk service spent 17 fewer days in hospital [95% CI: 33.7 to (-0.3)], had a shorter referral-to-diagnosis time [B coefficient -74.5 days, 95% CI: -101.9 to -(47.1)], a lower frequency of admission [IRR: 0.49 (95% CI: 0.39-0.61)] and a lower likelihood of compulsory admission [OR: 0.52 (95% CI: 0.34-0.81)] in the 24 months following referral, as compared to FEP patients who were first diagnosed at conventional services. CONCLUSION: Services for people at high risk for psychosis are associated with better clinical outcomes in patients who are already psychotic. PMID- 26358301 TI - Oral soft tissue infections: causes, therapeutic approaches and microbiological spectrum with focus on antibiotic treatment. AB - INTRODUCTION: Intraoral soft tissue infections (OSTI) are a common problem in dentistry and oral surgery. These abscesses are mostly exacerbated dental infections (OIDC), and some emerge as postoperative infections (POI) after tooth extraction (OITR) or apicoectomy (OIRR). The main aim of this study was to compare OIDC with POI, especially looking at the bacteria involved. An additional question was, therefore, if different antibiotic treatments should be used with OSTI of differing aetiologies. The impact of third molars on OSTI was evaluated and also the rates of POI after removal of third molars were specified. MATERIAL AND METHODS: Patient data was collected from the patients' medical records and the results were statistically evaluated with SPSS (SPSS version 21.0; SPSS, IBM; Chicago, IL, USA). The inclusion criterion was the outpatient treatment of a patient with an exacerbated oral infection; the exclusion criteria were an early stage of infiltration without abscess formation; and a need for inpatient treatment. RESULTS: Periapical exacerbated infections, especially in the molar region were the commonest cause of OIDC. In the OITR group, mandibular tooth removal was the commonest factor (p=0.016). Remarkably, retained lower wisdom teeth led to significant number of cases in the OITR group (p=0.022). CONCLUSIONS: In our study we could not define differences between the causal bacteria found in patients with OIDC and POI. Due to resistance rates we conclude that amoxicillin combined with clavulanic acid seems to be the antibiotic standard for exacerbated intraoral infections independent of their aetiology. PMID- 26358302 TI - Contemporary Management of Lower Extremity Venous Ulceration. Introduction. PMID- 26358304 TI - Pathogenesis of venous ulcer. AB - The underlying pathophysiology of venous ulceration is venous hypertension, which initiates a complex cascade of cellular humeral events that are then magnified by genetic factors. Hemodynamic abnormalities are features of primary and secondary chronic venous diseases that lead to disease progression. Through a sequence of events, some patients develop venous leg ulcers, if the process is not interrupted. The exact science of the pathophysiology of the progression of chronic venous disease to venous leg ulcers is still in its infancy, but the framework for future study has been established. PMID- 26358303 TI - Venous ulcers of the lower extremity: Definition, epidemiology, and economic and social burdens. AB - Venous ulcer is a common vascular condition affecting 1% of the population, and a prevalence that increases with age. Venous ulcer is defined by the American Venous Forum as "a full-thickness defect of skin, most frequently in the ankle region, that fails to heal spontaneously and is sustained by chronic venous disease, based on venous duplex ultrasound testing." The economic and social burden of this condition is significant to both the affected individual and the health care system. The recurrent nature of venous ulcers underscore the need for treatment of the underlying pathophysiology, that is, ambulatory venous hypertension produced by venous valve reflux alone or in conjunction with venous obstruction. PMID- 26358305 TI - Investigation of venous ulcers. AB - The evaluation of patients with venous ulceration primarily includes noninvasive methods to elucidate the distribution and extent of pathology. Duplex ultrasound is the first line of investigation, as it provides assessment of both reflux and obstruction conditions. In patients with iliofemoral pathology, axial imaging with computed tomography scan or magnetic resonance imaging should be performed. If the treatment of iliofemoral vein obstruction is warranted, then invasive assessment using venography and/or intravascular ultrasound should be used to guide the interventional procedure. Venous valve reflux can be identified and accurately characterized by duplex ultrasound, whereas the ultrasound assessment of functional abnormality associated with obstruction is less reliable. In patients with ulceration, the evaluation for and treatment of proximal venous obstruction has resulted in improved ulcer healing. PMID- 26358306 TI - Medical management of venous ulcers. AB - Venous disease is the most common cause of chronic leg ulceration and represents an advanced clinical manifestation of venous insufficiency. Due to their frequency and chronicity, venous ulcers have a high socioeconomic impact, with treatment costs accounting for 1% of the health care budget in Western countries. The evaluation of patients with venous ulcers should include a thorough medical history for prior deep venous thrombosis, assessment for an hypercoagulable state, and a physical examination. Use of the CEAP (clinical, etiology, anatomy, pathophysiology) Classification System and the revised Venous Clinical Severity Scoring System is strongly recommended to characterize disease severity and assess response to treatment. This venous condition requires lifestyle modification, with affected individuals performing daily intervals of leg elevation to control edema; use of elastic compression garments; and moderate physical activity, such as walking wearing below-knee elastic stockings. Meticulous skin care, treatment of dermatitis, and prompt treatment of cellulitis are important aspects of medical management. The pharmacology of chronic venous insufficiency and venous ulcers include essentially two medications: pentoxifylline and phlebotropic agents. The micronized purified flavonoid fraction is an effective adjunct to compression therapy in patients with large, chronic ulceration. PMID- 26358307 TI - Treatment of superficial venous incompetence. AB - Superficial venous incompetence is a common lower limb vascular condition, with venous ulceration representing the most severe sequela of the disease. The treatment of superficial venous incompetence can aid in ulcer healing, and a variety of modalities are available. Successful treatment requires attention to appropriate patient selection and procedural technique. PMID- 26358308 TI - Deep venous reconstructive surgery. AB - Surgical correction of deep venous reflux is a valuable adjunct in treatment of selected patient with lower limb venous ulcer. Deep venous obstruction and superficial reflux is must be corrected first. Sustained venous ulcer healing and reduced ambulatory venous hypertension can be achieved in patients with both primary and secondary deep venous insufficiency. When direct valve repair is possible, valvuloplasty is the best option, but when this is not feasible, other techniques can be used, including femoral vein transposition into the great saphenous vein, vein valve transplant, neovalve construction, or nonautologous artificial venous valve. PMID- 26358309 TI - Treatment of iliac-caval outflow obstruction. AB - The importance of the obstructive component in chronic venous disease (CVD) with ulceration has been emphasized recently for a venous condition that has primarily focused on the reflux component. Modern imaging techniques, particularly intravascular ultrasound, have shown the frequency of the obstructive element in both post-thrombotic and nonthrombotic disease. The emergence of iliac vein stent angioplasty and its good results in the treatment of large vein and other diverse CVD subsets has strengthened the role of obstruction. Lower-limb symptom diminution after iliac vein stenting in patients with concomitant reflux has been surprising, and has prompted a better understanding of CVD pathology. The technique of venous stenting differs from arterial in both technique and purpose. Mere restoration of forward flow is not sufficient; adequate decompression of the peripheral veins with reduction in ambulatory venous hypertension must be achieved. This requires implantation of large-diameter stents approximating normal anatomy. Stent recanalization of chronic total occlusions of the iliac caval segments-even long occlusions involving the entire inferior vena cava (IVC) can be successfully carried out, supplanting prior difficult open techniques, and this approach is applicable to patients with thrombosed IVC filters. Iliocaval stent angioplasty is safe, with low mortality and morbidity (<1%), and a cumulative patency ranging from 90% to 100% and 74% to 89% for nonthrombotic and post-thrombotic disease, respectively, at 3 to 5 years. Clinical relief of pain ranged from 86% to 94% and relief for swelling ranged from 66% to 89%; and 58% to 89% of venous ulcers healed. Procedural success in recanalization of chronic total occlusion lesions ranged from 83% to 95%, but long-term patency of stents in recanalized chronic total occlusion lesions is 10% to 20% lower than for stenotic lesions. Initial stent treatment does not preclude later open correction of obstruction or reflux in case of stent failure. These features, combined with the minimally invasive nature of the stent technique, have opened this avenue of treatment to a larger portion of the symptomatic CVD population. PMID- 26358310 TI - Algorithm-based approach to management of venous leg ulceration. AB - Management of venous ulceration has evolved tremendously during the last 2 decades. There has been considerable progress in our understanding of the pathophysiology, hemodynamics, venous imaging, and therapeutic options for venous ulcers, including endovenous ablation, iliac vein stenting, and vein-valve repair techniques. Details of these procedures are described in this issue of Seminars. With so many permutations and combinations of venous disease, including superficial and deep vein abnormalities, that produce venous ulceration, as well as a plethora of diagnostic and therapeutic tools at our disposal, it is important to have an algorithm for venous ulcer management. Also important is knowledge about risk factors that can influence poor outcomes, despite interventions for venous ulcers. In the end, authors also discuss the gray areas of venous ulcer management, which do not have common consensus and that treatment could be individualized based on patient needs. PMID- 26358311 TI - Paternal duplication of the 11p15 centromeric imprinting control region is associated with increased expression of CDKN1C in a child with Russell-Silver syndrome. PMID- 26358312 TI - Different mutation profiles and clinical characteristics among Hispanic patients with non-small cell lung cancer could explain the "Hispanic paradox". AB - OBJECTIVE: Sixteen percent of US population is Hispanic, mostly Mexican. Recently, two independent American reports demonstrated a higher overall survival (OS) in Hispanic populations compared with non-Hispanic-white populations (NHW) with non-small-cell lung cancer (NSCLC), even when most Hispanic patients are diagnosed at advanced disease stages and have lower income status. We analyzed the clinical, pathological, and molecular characteristics as well as outcomes in a cohort of NSCLC Hispanic patients from the National Cancer Institute of Mexico that could explain this "Hispanic Paradox". MATERIAL AND METHODS: A cohort of 1260 consecutive NSCLC patients treated at the National Cancer Institute of Mexico from 2007 to 2014 was analyzed. Their clinical-pathological characteristics, the presence of EGFR and KRAS mutations and the prognosis were evaluated. RESULTS: Patients presented with disease stages II, IIIa, IIIb and IV at rates of 0.6, 4.8, 18.4 and 76.3%, respectively. NSCLC was associated with smoking in only 56.5% of the patients (76.7% of male vs. 33.0% of female patients). Wood smoke exposure (WSE) was associated with 37.2% of the cases (27.3% in men vs. 48.8% in women). The frequency of EGFR mutations was 27.0% (18.5% in males vs. 36.9% in females, p<0.001) and the frequency for KRAS mutations was 10.5% (10.3% men vs. 10.1% in women p=0.939). The median OS for all patients was 23.0 [95% CI 19.4-26.2], whereas for patients at stage IV, it was 18.5 months [95% CI 15.2-21.8]. The independent factors associated with the OS were the ECOG, disease stage, EGFR and KRAS mutation status. CONCLUSION: The high frequency of EGFR mutations and low frequency of KRAS mutations in Hispanic populations and different prevalence in lung cancer-related-developing risk factors compared with Caucasian populations, such as the lower frequency of smoking exposure and higher WSE, particularly in women, might explain the prognosis differences between foreign-born-Hispanics, US-born-Hispanics and NHWs. PMID- 26358313 TI - The patient's perspective on stereotactic body radiation therapy (SBRT) vs. surgery for treatment of early stage non-small cell lung cancer (NSCLC). AB - OBJECTIVES: We investigated the patient's perspective on SBRT for treatment of stage I NSCLC and compared the patient's perspective of SBRT to that of surgery. MATERIALS AND METHODS: IRB approval was obtained to contact patients who had received SBRT for stage I NSCLCs. Patients were asked questions inquiring into their knowledge of SBRT and how their SBRT experience compared to their original expectations. Patients who had undergone prior surgery for a previously diagnosed stage I NSCLC were asked questions comparing their experience between SBRT and surgery. Frequencies of these reported measures were calculated and analysis was done using Fisher's exact test. RESULTS: 102 patients were contacted with 91 (89%) participating. Among all patients, prior to their radiation oncology consultation, 56% had no knowledge of SBRT and 58% believed SBRT to be as effective as resection. After consultation, 98.9% did not believe they were getting an inferior treatment with SBRT. 92.3% of patients reported less side effects, 59.3% reported SBRT to be more convenient and 87.9% reported SBRT to be less anxiety provoking than compared to their original expectations. Among patients with prior lung surgery (N=39), compared to surgery, 100% reported an easier recovery, less treatment related anxiety and less caregiver strain with SBRT. Overall, 79.5% were more satisfied with SBRT than surgery and 89.7% would have rather had SBRT than surgery as it was performed for their prior NSCLC. CONCLUSION: Actual experiences with SBRT are overwhelmingly superior compared to patient expectations. Patients with prior lung surgery reported significantly more satisfaction with SBRT. PMID- 26358314 TI - Assessment of a Microsoft Kinect-based 3D scanning system for taking body segment girth measurements: a comparison to ISAK and ISO standards. AB - Use of anthropometric data to infer sporting performance is increasing in popularity, particularly within elite sport programmes. Measurement typically follows standards set by the International Society for the Advancement of Kinanthropometry (ISAK). However, such techniques are time consuming, which reduces their practicality. Schranz et al. recently suggested 3D body scanners could replace current measurement techniques; however, current systems are costly. Recent interest in natural user interaction has led to a range of low cost depth cameras capable of producing 3D body scans, from which anthropometrics can be calculated. A scanning system comprising 4 depth cameras was used to scan 4 cylinders, representative of the body segments. Girth measurements were calculated from the 3D scans and compared to gold standard measurements. Requirements of a Level 1 ISAK practitioner were met in all 4 cylinders, and ISO standards for scan-derived girth measurements were met in the 2 larger cylinders only. A fixed measurement bias was identified that could be corrected with a simple offset factor. Further work is required to determine comparable performance across a wider range of measurements performed upon living participants. Nevertheless, findings of the study suggest such a system offers many advantages over current techniques, having a range of potential applications. PMID- 26358316 TI - Tiotropium - what role in asthma? AB - Tiotropium solution for inhalation (Spiriva Respimat - Boehringer Ingelheim) is the first long-acting muscarinic antagonist to be marketed in the UK for the management of asthma. It is licensed as add-on maintenance bronchodilator treatment in adults with asthma who are using an inhaled corticosteroid (>=800MUg budesonide/day or equivalent) and a long-acting beta2 agonist, and who have had one or more severe exacerbations in the previous year. This corresponds to use at step 4 of both the British asthma guideline and the Global Initiative for Asthma (GINA) strategy for the treatment of asthma in adults. Here we consider the evidence for tiotropium in the management of asthma and whether it offers any advantages over existing therapeutic options at step 4. PMID- 26358315 TI - Molecular characterization and quantification of the follicle-stimulating hormone receptor in turbot (Scophthalmus maximus). AB - Molecular cloning, characterization, and functional analysis of follicle stimulating hormone receptor (FSHR) in female turbot (Scophthalmus maximus) were evaluated. Results showed that the full-length FSHR cDNA was 3824 bp long and contained a 2202 bp open reading frame that encoded a mature protein of 733 amino acids (aa) and a signal peptide of 18 aa. Multiple sequence analyses showed that turbot FSHR has high homology with the corresponding genes of other teleosts and significant homology with that of Hippoglossus hippoglossus. Turbot FSHR has the typical structural architecture of glycoprotein hormone receptors consisting of a large N-terminal extracellular domain, seven transmembrane domains and short C terminal intracellular domain. FSHR mRNA was found to be abundant in the ovaries, but deficient in eyes, intestine, brain, muscle, gills, spleen, stomach, heart and kidney. Furthermore, FSHR mRNA was found to increase gradually from pre vitellogenesis to migratory nucleus stages, with the highest values observed during the late vitellogenesis stage of the reproductive cycle. However, FSHR mRNA was found to decrease dramatically during the atresia stage. Meanwhile, functional analysis with HEK293T cells continual expressing FSHR demonstrated that FSHR was specifically stimulated by ovine FSH, but not ovine LH. These results indicate that turbot FSHR is mainly involved in the stimulation of vitellogenesis, regulation of oocyte maturation as well as promotion of ovarian development via specific ligand binding. These findings open doors to further investigation of physiological functions of FSHR, which will be valuable for fish reproduction and broodstock management. PMID- 26358317 TI - ? Apremilast for psoriasis and psoriatic arthritis. AB - ? Apremilast (Otezla - Celgene Europe Ltd.) is a novel orally administered immunomodulatory medicine licensed for the treatment of plaque psoriasis and psoriatic arthritis. The company suggests that it has demonstrated proven and durable efficacy in both conditions and has a favourable safety profile with no requirement for drug-specific pre-screening or ongoing laboratory monitoring. Here we review the evidence on the safety and efficacy of apremilast in the management of psoriasis and psoriatic arthritis. PMID- 26358318 TI - A secondary analysis to determine variations of dental arch measurements with age and gender among Ugandans. AB - BACKGROUND: Dental arch dimensions are useful in dental practice and in forensic odontology. Local data is essential because ethnic differences exist in dental arch dimensions. In the Ugandan population no studies had been done on dental arch dimensions. The objective of the current study was to determine the variations in dental arch dimensions with age and gender in a sample of dental casts from the Ugandan population. METHOD: This was a secondary analysis of dental casts previously prepared using mandibular and maxillary arch impressions of 220 children (85 boys and 135 girls) aged 12-17 years recruited from schools in Kampala, Uganda. Dental arch dimensions for the maxilla and mandibular casts were taken using a digital vernier calliper. The data was analysed using the means based independent samples t test to obtain the descriptive statistics with regression analysis being used to obtain the regression coefficients and constants using STATA 12. RESULTS: The overall maxillary dimensions were significantly smaller in females than males by 1.50 mm (95% CI -2.91 to -0.09, P = 0.04), controlling for age group. The overall dimensions of the mandible were also smaller in younger participants, though this was not statistically significant. CONCLUSION: From this study we observed significant differences in arch dimensions between males and females that are of forensic value for this population. There is need for more study of the differences in arch dimensions with age using a larger and more age diverse study population. PMID- 26358320 TI - GAS2-Calpain2 axis contributes to the growth of leukemic cells. AB - Growth arrest specific 2 (GAS2) modulates cell cycle, apoptosis, and Calpain activity. GAS2-Calpain2 axis is required for the growth of BCR-ABL(+) hematopoietic cells and chronic myeloid leukemia cells. However, the expression of GAS2 in acute leukemia patients remains unclear and what role GAS2-Calpain2 axis plays in these leukemic cells is not known yet. In this study, GAS2 was found to have significantly higher expression in 16 various leukemic cell lines than in control cells. Using THP-1 cells (from acute myeloid leukemia patient, AML) and Jurkat cells (from acute lymphoid leukemia patient, ALL) as models, we found that GAS2 silence led to elevated Calpain activity, decreased cellular growth, and inhibition of colony-forming cell (CFC) production; and these effects could be rescued by GAS2 re-expression. Moreover, GAS2 silence prevented tumor formation of THP-1 cells in nude mice. In both THP-1 and Jurkat cells, GAS2 interacted with Calpain2 rather than Calpain1. The dominant negative form of GAS2 (GAS2DN, GAS2Delta171-313) had similar effects on leukemic cells through the activation of Calpain. Importantly, Calpain2 silence abolished the proliferation inhibition induced by GAS2 targeting. We also found that GAS2 was aberrantly expressed and Calpain activity was decreased in clinical isolates from acute leukemia patients. Taken together, our results demonstrated the deregulation of GAS2 in both AML and ALL and the requirement of GAS2-Calpain2 axis for the growth of leukemic cells, which will help to understand the molecular pathogenesis of hematological malignancies and possibly to develop novel approaches to treat these deadly diseases. PMID- 26358319 TI - Glycosaminoglycan derivatives: promising candidates for the design of functional biomaterials. AB - Numerous biological processes (tissue formation, remodelling and healing) are strongly influenced by the cellular microenvironment. Glycosaminoglycans (GAGs) are important components of the native extracellular matrix (ECM) able to interact with biological mediator proteins. They can be chemically functionalized and thereby modified in their interaction profiles. Thus, they are promising candidates for functional biomaterials to control healing processes in particular in health-compromised patients. Biophysical studies show that the interaction profiles between mediator proteins and GAGs are strongly influenced by (i) sulphation degree, (ii) sulphation pattern, and (iii) composition and structure of the carbohydrate backbone. Hyaluronan derivatives demonstrate a higher binding strength in their interaction with biological mediators than chondroitin sulphate for a comparable sulphation degree. Furthermore sulphated GAG derivatives alter the interaction profile of mediator proteins with their cell receptors or solute native interaction partners. These results are in line with biological effects on cells relevant for wound healing processes. This is valid for solute GAGs as well as those incorporated in collagen-based artificial ECM (aECMs). Prominent effects are (i) anti-inflammatory, immunomodulatory properties towards macrophages/dendritic cells, (ii) enhanced osteogenic differentiation of human mesenchymal stromal cells, (iii) altered differentiation of fibroblasts to myofibroblasts, (iv) reduced osteoclast activity and (v) improved osseointegration of dental implants in minipigs. The findings of our consortium Transregio 67 contribute to an improved understanding of structure-function relationships of GAG derivatives in their interaction with mediator proteins and cells. This will enable the design of bioinspired, functional biomaterials to selectively control and promote bone and skin regeneration. PMID- 26358321 TI - Antitumor activity of fucoidan against diffuse large B cell lymphoma in vitro and in vivo. AB - Fucoidan is one of the major sulfated polysaccharides isolated from brown seaweeds. In this study, we determined the anti-cancer activity of fucoidan on diffuse large B cell lymphoma (DLBCL) cells both in vitro and in vivo. Fucoidan inhibited the growth of DLBCL cells in a dose- and time-dependent manner, and fucoidan treatment provoked G0/G1 cell cycle arrest, which was accompanied by p21 up-regulation and cyclin D1, Cdk4, and Cdk6 down-regulation. Fucoidan also induced caspase-dependent cell apoptosis in DLBCL cell lines and primary DLBCL cell. In addition, fucoidan treatment caused the loss of mitochondrial membrane potential and the release of cytochrome c and apoptosis-inducing factor from the mitochondria into the cytosol. Fucoidan also potentiated the activities of carfilzomib in killing DLBCL cells. Oral administration of fucoidan effectively inhibited tumor growth in xenograft mouse models. Our findings reveal the novel function of fucoidan as an anti-DLBCL agent, which can be used in the clinical treatment of DLBCL. PMID- 26358322 TI - [Augmentation with antibiotic-impregnated spacers in sepsis revision surgery]. AB - BACKGROUND: The development of antibiotic-impregnated polymethyl methacrylate (PMMA) spacers is based on clinical experience and the use of antibiotic-loaded PMMA beads in septic bone surgery as well as antibiotic-loaded bone cement in arthroplasty beginning in the 1970s. MATERIAL AND METHODS: In the meantime hand formed and prefabricated spacers are implanted in cases of sepsis to achieve high local antibiotic concentrations and bactericidal effects to eradicate the infection. Preformed spacers with gentamicin are commercially available and furthermore, clindamycin-loaded PMMA bone cement can also be used. In principle, all thermostable antibiotics can be mixed with PMMA cement. SIGNIFICANCE: Spacers permit bridging of bone defects originating from trauma or septic bone segment resection. After joint resection spacers allow a certain degree of articulation and inhibit shortening of the extremity which has a positive effect on the soft tissue covering and its perfusion. CONCLUSION: The functional outcome after secondary arthroplasty is better if a spacer has been implanted compared to long term immobilization without spacers. Nevertheless, spacers can also cause serious complications, such as dislocations and fractures. Antibiotic-loaded spacers have therefore widened the therapeutic options in sepsis surgery. PMID- 26358323 TI - [Biomechanical aspects of vertebral augmentation]. AB - BACKGROUND: With increasing age, bone mass decreases and the structure of the cancellous bone in the vertebral body changes. Especially in osteoporotic patients, but also with metastases in the vertebral body, this leads to decreased strength and, thus, to an increased risk of vertebral fractures. It is expected that this problem will increase significantly because of demographic developments. To treat or to prevent such vertebral fractures, different augmentation techniques have been developed. They can mainly be divided into vertebroplasty or kyphoplasty procedures. PURPOSE: The goal of this paper is to summarize biomechanical aspects of these augmentations procedures and to present some alternative methods. MATERIALS AND METHODS: With vertebroplasty, the loss of bone mass is balanced by injecting bone cement which improves the failure strength of the affected vertebral body. With kyphoplasty, cavities are created and these are filled with bone cement. RESULTS: Disadvantages of vertebroplasty are uncontrollable cement extrusion and increased fracture risk in the adjacent vertebral bodies. With balloon kyphoplasty, the adjacent cancellous bone is compacted during dilation and, thus, does not allow good integration with the remaining trabeculae. In addition, this method is associated with an increased risk of fracture in the adjacent vertebrae. To counter these disadvantages, a number of new types of cement and alternative augmentation methods are being developed, with which the vertebral body may be filled or distracted. CONCLUSION: The efficacy of these new methods should be tested in appropriate experimental biomechanical studies before they are used in patients. PMID- 26358324 TI - Anomalous origin of the right coronary artery from the pulmonary artery: surgical re-implantation into the aorta. AB - Anomalous origin of the right coronary artery from the pulmonary artery is rare (only 200 cases have been reported in total), potentially life-threatening and with an uncertain prognosis. Patient characteristics are only available in half the reported cases. Easy to miss, anomalous origin of the right coronary artery from the pulmonary artery (ARCAPA) is usually diagnosed in association with concomitant cardiac anomalies. Techniques for its correction are rarely discussed, but the restoration of a two-coronary system is optimal. We report details of the surgical repair of ARCAPA in a 17-year-old man to highlight important anatomical features. PMID- 26358325 TI - The pocket-creation method of ESD for gastric neoplasms. PMID- 26358326 TI - Septotomy: an adjunct endoscopic treatment for post-sleeve gastrectomy fistulas. PMID- 26358327 TI - Argon plasma coagulation: a less-expensive alternative to the "stent-in-stent" technique for removal of embedded partially covered esophageal stents. PMID- 26358328 TI - Underwater peroral endoscopic myotomy. PMID- 26358329 TI - Limited applicability of chromoendoscopy-guided confocal laser endomicroscopy as daily-practice surveillance strategy in Crohn's disease. AB - BACKGROUND AND AIMS: Patients with longstanding ulcerative colitis have an increased risk for developing colorectal cancer (CRC). Although the risk for ulcerative colitis is well-established, for Crohn's disease data are contradictory. This study aimed to determine the number of patients with Crohn's disease with dysplasia who are undergoing surveillance and to assess the diagnostic accuracy of chromoendoscopy (CE) combined with integrated confocal laser endomicroscopy (iCLE) for differentiating dysplastic versus nondysplastic lesions. METHODS: Patients with longstanding Crohn's colitis undergoing surveillance colonoscopy were included in this multicenter, prospective, cohort study. Surveillance was performed with CE, and lesions were assessed with iCLE for differentiation. All lesions were removed and sent for pathology as the reference standard. RESULTS: Between 2010 and 2014, a total of 61 patients with Crohn's colitis were included in 5 centers. Seventy-two lesions, of which 7 were dysplastic, were detected in 6 patients (dysplasia detection rate 9.8%); none included high-grade dysplasia or cancer. Combined CE with iCLE for differentiating neoplastic from nonneoplastic lesions had accuracy of 86.7% (95% confidence interval [CI], 78.1-95.3), sensitivity of 42.9% (95% CI, 11.8-79.8), and specificity of 92.4% (95% CI, 80.9-97.6). For CE alone, this was 80.3% (95% CI, 70.7-89.9), 28.6% (95% CI, 5.1-69.7), and 86.4% (95% CI, 80.9-97.6). The study terminated early because of frequent failure of the endoscopic equipment. CONCLUSIONS: This study shows a low incidence of dysplastic lesions found during surveillance colonoscopy in patients with longstanding extensive Crohn's colitis. The accuracy of both CE alone and CE in combination with iCLE was relatively good, although the sensitivity for both was poor. Because of frequent equipment failure, iCLE has limited applicability in daily practice as a surveillance strategy. PMID- 26358330 TI - EUS-guided portal injection chemotherapy for treatment of hepatic metastases: feasibility in the acute porcine model. AB - BACKGROUND AND AIMS: Direct injection of chemotherapy into the portal vein for treatment of liver metastases may increase hepatic tissue levels while decreasing systemic levels and toxicities. We aimed to evaluate EUS-guided portal injection chemotherapy (EPIC) by using drug-eluting microbeads or nanoparticles and compare it with systemic injection. METHODS: We conducted a comparative feasibility trial in the acute porcine model (24 anesthetized pigs). Pigs were treated with irinotecan, doxorubicin, or albumin-bound paclitaxel nanoparticles (n = 8/group). Within each group, pigs were treated with EPIC or a systemic intravenous injection of drug and saline solution into the portal vein (n = 4/treatment). Irinotecan or doxorubicin were loaded onto microbeads for EPIC treatment only. We examined drug levels in tissue (1 hour) and plasma (15 minutes). RESULTS: EUS guided access and injection was successful in all animals. EPIC with irinotecan loaded microbeads showed nearly double the hepatic concentration compared with systemic injection (6242 vs 3692 ng/g) and almost half the systemic levels. EPIC with doxorubicin-loaded microbeads showed a 5-fold increase in hepatic levels (35,450 vs 6930 ng/g) and a 30-fold decrease in cardiac levels (153 vs 4805 ng/g) compared with systemic administration (P < .05 for both). EPIC with albumin-bound paclitaxel nanoparticles increased hepatic concentrations by 60% and decreased systemic levels by 24% to 32%. CONCLUSIONS: EPIC holds promise as a new treatment for hepatic metastases. PMID- 26358331 TI - A prospective randomized comparative study of cold forceps polypectomy by using narrow-band imaging endoscopy versus cold snare polypectomy in patients with diminutive colorectal polyps. AB - BACKGROUND AND AIMS: A previous study reported that cold snare polypectomy (CSP) was superior to cold forceps polypectomy (CFP) for the removal of diminutive colorectal polyps (DCPs) (<=5 mm) when the techniques were assessed for completeness of resection. However, completeness is expected to be greater with CFP when strict investigation of the remnant polyp is performed. The aim of this study was to assess the efficacy of CFP with narrow-band imaging (NBI) evaluation of polypectomy sites for removal of DCPs, compared with CSP. METHODS: This was a randomized, controlled, noninferiority trial at a tertiary-care referral hospital. Of the 380 patients screened, 146 patients with 231 DCPs were enrolled. CFP was used to resect DCPs until no remnant polyp was visible by NBI endoscopy. The primary noninferiority endpoint was histologic eradication of polyps, with a noninferiority margin of -10%. RESULTS: A size of >3 mm was seen in 129 polyps (55.8%). The overall rates of histologic eradication were 90.5% in the CFP group and 93.0% in the CSP group (difference, 2.5%; 95% confidence interval [CI], -9.67 to 4.62). However, when confined to the polyps >3 mm, the histologic eradication rate was 86.8% and 93.4% (95% CI, -17.2 to 3.6), respectively. Polyp size, histology, location, and time taken for polypectomy did not differ between the groups. The failure rate of tissue retrieval was higher in the CSP than in the CFP group (7.8% vs 0.0%, respectively; P =.001). CONCLUSIONS: In this study, >90% of all DCPs were completely resected by using CFP with NBI evaluation of polypectomy sites, showing noninferiority compared with CSP. However, in polyps measuring >3 mm, CFP failed to show noninferiority versus CSP. CFP appears to be the proper method for resection of DCPs 1 to 3 mm in size if no remnant polyp is visible by NBI endoscopy, but CFP is likely to be insufficient for larger polyps. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT02201147.). PMID- 26358332 TI - Evaluation of patients' knowledge on warfarin in outpatient pharmacy of a tertiary care cardiac center. AB - BACKGROUND: Warfarin is widely used for the prevention and treatment of cardiac, thromboembolic and hypercoagulable diseases. Since warfarin is a narrow therapeutic index medicine, it requires close monitoring when used in the outpatient setting and on long term basis. Warfarin has been found to be associated with a number of complications especially bleeding. Patients' knowledge on warfarin can improve anticoagulation control with decrease in adverse drug reaction and other associated complications. The objective was to assess knowledge level of warfarin therapy among its users and to provide adequate education and counseling to the patients. METHODS: In the present cross sectional study, 34 patients on warfarin were interviewed. Patients' knowledge on warfarin was assessed using a validated Anticoagulation Knowledge Assessment (AKA) questionnaire comprising 29 questions. Each correct answer scored 3.45 points whereas an incorrect answer scored zero point. Patient who answered at least 21 questions correctly or scored (21 * 3.45 = 72.4%) was considered to have adequate level of knowledge or have obtained a passing score. Association between independent variables and AKA score was assessed using Pearson Chi square test or Fisher's exact test for categorical variables. Patients were counseled regarding proper warfarin use by the researcher pharmacists at the end of each data collection schedule. RESULTS: Of the 34 patients, only 5.8% (n = 2) achieved a passing score whereas 94.1% (n = 32) failed to achieve the passing score. 67.6% of the patients (n = 23) achieved a score below 50%. More than 50% of the patients incorrectly answered 15 questions in the questionnaire. None of the patients scored 100%. No significant association was found between age, gender of patients and total warfarin score. A significant association (p < 0.05) was found between duration of warfarin therapy and total warfarin score. CONCLUSIONS: Warfarin knowledge was poor among the patients. Hence, regular counseling with timely assessment of their understanding was felt necessary. PMID- 26358333 TI - Molecular dynamics simulations on PGLa using NMR orientational constraints. AB - NMR data obtained by solid state NMR from anisotropic samples are used as orientational constraints in molecular dynamics simulations for determining the structure and dynamics of the PGLa peptide within a membrane environment. For the simulation the recently developed molecular dynamics with orientational constraints technique (MDOC) is used. This method introduces orientation dependent pseudo-forces into the COSMOS-NMR force field. Acting during a molecular dynamics simulation these forces drive molecular rotations, re orientations and folding in such a way that the motional time-averages of the tensorial NMR properties are consistent with the experimentally measured NMR parameters. This MDOC strategy does not depend on the initial choice of atomic coordinates, and is in principle suitable for any flexible and mobile kind of molecule; and it is of course possible to account for flexible parts of peptides or their side-chains. MDOC has been applied to the antimicrobial peptide PGLa and a related dimer model. With these simulations it was possible to reproduce most NMR parameters within the experimental error bounds. The alignment, conformation and order parameters of the membrane-bound molecule and its dimer were directly derived with MDOC from the NMR data. Furthermore, this new approach yielded for the first time the distribution of segmental orientations with respect to the membrane and the order parameter tensors of the dimer systems. It was demonstrated the deuterium splittings measured at the peptide to lipid ratio of 1/50 are consistent with a membrane spanning orientation of the peptide. PMID- 26358334 TI - Accelerated one-step generation of full-color holographic videos using a color tunable novel-look-up-table method for holographic three-dimensional television broadcasting. AB - A color-tunable novel-look-up-table (CT-NLUT) for fast one-step calculation of full-color computer-generated holograms is proposed. The proposed method is composed of four principal fringe patterns (PFPs) such as a baseline, a depth compensating and two color-compensating PFPs. CGH patterns for one color are calculated by combined use of baseline-PFP and depth-compensating-PFP and from them, those for two other colors are generated by being multiplied by the corresponding color-compensating-PFPs. color-compensating-PFPs compensate for differences in the wavelength between two colors based on their unique achromatic thin-lens properties, enabling transformation of one-color CGH pattern into those for other colors. This color-conversion property of the proposed method enables simultaneous generation of full color-CGH patterns, resulting in a significant reduction of the full color-CGH calculation time. Experimental results with test scenario show that the full color-CGH calculation time of the proposed CT-NLUT has been reduced by 45.10%, compared to the conventional NLUT. It has been further reduced by 96.01% when a data compression algorithm, called temporal redundancy-based NLUT, was used together, which means 25-fold reduction of its full color-CGH calculation time. Successful computational and optical reconstructions of full color-CGH patterns confirm the feasibility of the proposed method. PMID- 26358335 TI - Phospholipase A2-dependent release of inflammatory cytokines by superantigen stimulated nasal polyps of patients with chronic rhinosinusitis. AB - BACKGROUND: Chronic rhinosinusitis (CRS) is an inflammatory/allergic disease with unclear pathophysiology, but it has been linked to an imbalance in the production of eicosanoids, which are metabolites of arachidonic acid, and results from phospholipids hydrolysis by phospholipase A2 (PLA2). As of yet, the role of PLA2 in CRS has hardly been studied, except for a report that group II PLA2 expression is elevated in interleukin (IL) 1beta or tumor necrosis factor alpha-stimulated CRS nasal tissues with and without polyps. The PLA2 families include extracellular (secretory) and intracellular isoforms, which are involved in the regulation of inflammatory processes in different ways. Here we comprehensively investigated the expression of PLA2s, particularly those reported to be involved in respiratory disorders, in superantigen (SAE)-stimulated nasal polyps from patients with CRS with polyps, and determined their role in inflammatory cytokine production by inhibition of PLA2 expression. METHODS: The release of IL-5, IL-13, IL-17, and interferon gamma by nasal polyps dispersed cells (NPDC) was determined concomitantly with PLA2 messenger RNA expression, under SAE stimulation, with or without dexamethasone, as a regulator of PLA2 expression. RESULTS: Stimulation of NPDCs by SAE-induced cytokine secretion with enhanced expression of several secretory PLA2 and Ca(2+)-independent PLA2, while suppressing cytosolic PLA2 expression. All these were reverted to the level of unstimulated NPDCs on treatment with dexamethasone. CONCLUSION: This study further supports the key role of secretory PLA2 in the pathophysiology of respiratory disorders and presents secretory PLA2 inhibition as a therapeutic strategy for the treatment of CRS and airway pathologies in general. PMID- 26358336 TI - Efficacy evaluation of a pollen blocker cream against dust-mite allergy: A multicenter, randomized, double-blind, placebo-controlled crossover trial. AB - OBJECTIVE: To further evaluate the efficacy and safety of a pollen blocker cream against dust-mite allergy. METHODS: A multicenter, randomized, double-blind, placebo-controlled, crossover trial was conducted in a Chinese population. Patients diagnosed with perennial allergic rhinitis, sensitive to dust-mite allergy including Dermatophagoides farinae and Dermatophagoides pteronyssinus were randomly allocated to receive a pollen blocker cream or placebo, which was applied and spread evenly to the lower internal nose region three times daily for a total of 30 days. The primary outcome measurements for efficacy were total nasal symptom score (TNSS) and individual nasal symptom score (iNSS). Adverse events were also monitored. RESULTS: After application of a pollen blocker, the mean TNSS decreased from 23.1 to 13.8, the decrease of the pollen blocker group (9.3) was highly significant compared with the placebo group (5.2; p < 0.001). Similarly, the decreases in iNSSs (rhinorrhea, congestion, sneezing, and itching) between the pollen blocker group and the placebo group were also significant (p < 0.05). In addition, in adults, the pollen blocker led to a remarkably significant decrease in TNSS (9.5) compared with placebo (5.4; p < 0.001); in children, the pollen blocker led to a significant decrease in TNSS (8.6) compared with placebo (4.8; p < 0.05). No statistical difference was found in the incidence of adverse events between the two groups (p > 0.05), and no severe systematic reactions were observed. CONCLUSION: Pollen Blocker is a safe and effective alternative to the drugs for treatment of AR, especially for Chinese people allergic to dust-mite allergy. PMID- 26358337 TI - Radiofrequency turbinoplasty for nonallergic rhinitis in geriatric patients. AB - BACKGROUND AND OBJECTIVE: Radiofrequency (RF) turbinoplasty may be effective in treating nonallergic rhinitis in elderly patients. The present study evaluated the efficacy of nasal turbinate surgery with RF for the treatment of nonallergic rhinitis in elderly patients refractory to medical therapy. METHODS: A total of 35 consecutive patients older than 65 years of age (mean subject age, 75.5 +/- 9.6 [standard deviation] years) with nonallergic rhinitis refractory to medical therapy who underwent RF turbinate surgery were enrolled in this study. The efficacy of RF turbinoplasty in treating nonallergic rhinitis in elderly patients was evaluated by using rhinoscopy and a visual analog scale score of nasal symptoms. RESULTS: The response rate of primary RF turbinate surgery for nonallergic rhinitis refractory to medical therapy was 68.6%. Postoperative symptom scores for rhinorrhea and nasal obstruction were significantly improved. Persistent crust formation developed in seven patients (20.0%). No patient experienced major complications (e.g., septal hematoma, abscess, septal perforation), but partial bone necrosis was observed in one patient. CONCLUSION: RF turbinoplasty appeared to be effective for treating some nonallergic rhinitis symptoms in elderly patients, including rhinorrhea and nasal obstruction. These preliminary results are encouraging and warrant further investigation. PMID- 26358338 TI - Cross-culturally modified University of Pennsylvania Smell Identification Test for a Turkish population. AB - BACKGROUND: The University of Pennsylvania Smell Identification Test (UPSIT) is a well-developed and popular olfactory test, which has been validated in various populations. However, there was only one study in a Turkish population, and this study indicated that the North American version of the UPSIT was not enough to evaluate the olfactory functions of Turkish population. So, we developed a cross cultural adaptation of the UPSIT, the UPSIT-Turkish (UPSIT-T). Thus, the goal of this study was to investigate the applicability of the UPSIT-T in healthy Turkish subjects. MATERIAL AND METHODS: The study included 51 healthy individuals who reported having normal olfactory function. The participants were administered the North American version of the UPSIT firstly, and then, after a day UPSIT-T was applied to the participants. The results of two smell tests were compared, and the applicability of UPSIT-T was evaluated. RESULTS: The mean (standard deviation) value for correctly identified odors was 27.2 +/- 5.7 (range, 14-38) with the UPSIT application, whereas the mean (standard deviation) value for correctly identified odors was 35.9 +/- 3.1 for UPSIT-T. There was a statistically significant increase in the scores of the participants when UPSIT-T was performed (p < 0.001). The identification rates of 10 test odorants were <80% for our study group, and 2 of 10 were <70% for the UPSIT-T. CONCLUSION: The UPSIT T modification is an adequate olfactory test for clinical use in a Turkish population. PMID- 26358339 TI - Case definitions for chronic rhinosinusitis in administrative data: A systematic review. AB - BACKGROUND: The use of administrative data for pharmacoepidemiologic research on chronic rhinosinusitis (CRS) has become increasingly popular. Although large sample sizes and ease of accessibility have made electronic health data an attractive data option, the risk of inaccurate cohort identification can lead to biased outcomes. OBJECTIVES: The objectives of this systematic review were to (1) report current case definitions for CRS used in administrative data base research, and (2) define the various administrative data bases used for CRS research. METHODS: Medical literature data bases were searched from the date of their inception to February 1, 2015. Included studies were publications that obtained CRS-specific data from a health records data base. Studies were excluded if they evaluated a non-CRS cohort, failed to use or report an international classification of disease (ICD) code in the case definition, or published in a non-peer-reviewed journal. RESULTS: Of the 27 studies that met inclusion criteria, 8 different CRS case definitions were identified and 13 administrative data bases were evaluated. Of the 8 different CRS case definitions identified, only one was validated. The most commonly used CRS case definition was the ICD-9 473.x code alone. CONCLUSION: To optimize the accuracy of pharmacoepidemiologic research for CRS that used administrative data, it is important to apply appropriate case definitions for CRS. Various nonvalidated CRS case definitions are currently being used in administrative data base research. There is a need to develop a generalizable and validated ICD-based CRS case definition to increase the accuracy of future pharmacoepidemiologic research. PMID- 26358340 TI - Editorial: Inflammatory and allergic diseases of the upper airways. PMID- 26358341 TI - Expression profiles of prostaglandin E2 receptor subtypes in aspirin tolerant adult Chinese with chronic rhinosinusitis. AB - BACKGROUND: Several studies have indicated that prostaglandin E2 and E-prostanoid (EP) receptors play a role in the pathogenesis of chronic rhinosinusitis (CRS) in white populations. However, until now there was no report about EP receptor expression and its role in the pathophysiology of CRS in Chinese patients. OBJECTIVE: To investigate the expression profiles of EP receptors, including EP1, EP2, EP3, and EP4 receptors in different Chinese patients with CRS with aspirin tolerance. METHODS: Nasal biopsy specimens were obtained from 12 controls, 12 patients with CRS without nasal polyps (CRSsNP), 12 with eosinophilic CRS with nasal polyps (CRSwNP), and 16 with noneosinophilic CRSwNP. Histopathologic characteristics were observed under a light microscope. Immunostaining was used to examine tissue localization of EP receptors. Messenger RNA and protein expression of EP receptors were examined by means of quantitative RT-polymerase chain reaction and Western blot, respectively. RESULTS: Different types of CRS presented different histopathologic hallmarks. EP receptors were expressed mainly on epithelium, glands, and infiltrating inflammatory cells in nasal tissue. In controls, patients with CRSsNP, and those with noneosinophilic CRSwNP, EP4 mRNA levels were higher than EP1, EP2, and EP3 receptors. EP2 was downexpressed, and EP1 was upexpressed in patients with eosinophilic CRSwNP. When comparing EP receptor expression among different groups, Messenger RNA and protein of EP1 receptor were significantly enhanced in eosinophilic CRSwNP, but EP2, EP3, and EP4 receptors did not show significant differences. CONCLUSION: EP receptor expressions present different features in healthy subjects and patients with CRS. The upregulated EP1 receptor in eosinophilic CRSwNP might be associated with excessive infiltrations of eosinophils and other inflammatory cells. The accurate role of the four EP receptors in the pathogenesis of different CRS remains to be further explored. PMID- 26358342 TI - Serum indolamine 2,3 dioxygenase as a marker in the evaluation of allergic rhinitis. AB - BACKGROUND: Allergic rhinitis occurs on exposure to a known allergen and is correlated with a positive skin test and physical examination results. Tryptophan is a substrate of many important proteins, e.g., indolamine 2,3 dioxygenase (IDO). IDO, an immunomodulator, is a metabolic enzyme induced by immune activation. It has a significant role in allergic reactions. T-helper 2 cell is proposed to affect the expression of IDO. AIM: To evaluate IDO levels in patients with allergic rhinitis compared with controls and its relationship to the severity of allergic rhinitis. METHODS: This case-control study included 20 patients who were atopic and with allergic rhinitis who attended the allergy clinic of Ain Shams University Hospitals. Twenty age- and sex-matched patients who were not atopic were included as controls. An allergic rhinitis diagnosis was made according to the Allergic Rhinitis and its Impact on Asthma document. Complete history taking, physical examination, skin-prick test, complete blood cell count, erythrocyte sedimentation rate, total serum immunoglobulin E (IgE), IDO concentration, and nasal smear for eosinophils were done for the patients. RESULTS: There was a significant increase in IDO levels in allergic rhinitis in comparison with subjects without allergy (p < 0.001). IDO was positively correlated with total IgE levels (p < 0.037). There was an insignificant relationship among IDO levels and age, sex, duration of the disease, severity score, nasal and blood eosinophilia, and number of positive allergens. CONCLUSION: IDO plays an important role in patients with atopic symptomatic allergic rhinitis, especially with increased levels of IgE. There is no relationship between IDO levels and severity of disease. PMID- 26358343 TI - Secretion rates of human nasal submucosal glands from patients with chronic rhinosinusitis or cystic fibrosis. AB - BACKGROUND: A majority of patients with cystic fibrosis (CF) have chronic rhinosinusitis (CRS) and/or nasal polyps, both of which may be secondary to reduced fluid secretion from nasal submucosal glands. OBJECTIVE: To determine whether decreased fluid secretion from nasal submucosal glands also occurs in patients without CF and with CRS. METHODS: Inferior turbinates of the nasal cavity were harvested from controls, subjects with CRS, and subjects with CF (n = 5-7 per group). The secretion rates of the nasal submucosal glands of the three groups in response to carbachol and forskolin were measured by using time lapse digital imaging of mucus bubbles from single glands as they formed on the mucosal surface under oil. RESULTS: Carbachol-stimulated secretion rates were the following: controls, 1670 +/- 381 pl.min(-1).gland(-1); CRS, 965 +/- 440 pl.min( 1).gland(-1); and CF, 933 +/- 588 pl.min(-1).gland(-1) (p = 0.23, Kruskal-Wallis test). Forskolin-stimulated secretion rates were the following: controls, 229 +/- 14 pl.min(-1).gland(-1); CRS, 154 +/- 48 pl.min(-1).gland(-1); and CF, 22 +/- 15 pl.min(-1).gland(-1) (p = 0.008, Kruskal-Wallis test). The ratio of the average secretion rate induced by forskolin to that induced by carbachol was 13.7% in the controls, and 15.9% in CRS and 2.3% in CF groups. CONCLUSION: The only significant difference in this small study was decreased forskolin-stimulated secretion in subjects with CF relative to the other subjects. However, there was a trend toward reduced carbachol-stimulated secretion rates in subjects with CRS and with and without CF relative to controls. Additional studies are needed to determine if nasal submucosal gland hyposecretion occurs in CRS either as a contributor to or as a consequence of CRS pathogenesis. PMID- 26358344 TI - Oral corticosteroids in the management of chronic rhinosinusitis with and without nasal polyps: Risks and benefits. AB - BACKGROUND: Oral steroids are synthetic mimics of adrenal cortex hormones and are considered a staple in the management of chronic rhinosinusitis due to their anti inflammatory effects. Despite their common use, many providers are not familiar with the potential risks of the drugs. METHODS: Literature review. RESULTS: An overview of the existing data on the risks of oral steroids is presented as well as a review of the malpractice lawsuits with regard to oral steroid use and a discussion of the data that support the use of oral steroids in patients with chronic rhinosinusitis with and those without nasal polyps. CONCLUSION: It is essential for providers to be aware of the potential complications of a medication, the medical jurisprudence of the drugs, and the data that support their use. PMID- 26358345 TI - Clinical efficacy of nasal steroids on nonallergic rhinitis and the associated inflammatory cell phenotypes. AB - BACKGROUND: Although good response to nasal steroid therapy has been documented in allergic rhinitis (AR), the efficacy of this treatment in non-AR, and the associated inflammatory cell phenotypes has not been fully investigated. OBJECTIVE: To compare the response to steroids in non-AR versus AR and to assess the impact of inflammatory cell phenotypes on non-AR treatment outcomes. METHODS: A total of 149 patients with rhinitis were divided into non-AR and AR groups by using the allergy skin-prick test. Based on nasal cytology, the non-AR group was further divided into inflammatory non-AR (INAR) and noninflammatory non-AR (NINAR) groups, and the INAR groups were further subdivided into four phenotypes according to inflammatory cell type: non-AR with eosinophils (NARES), non-AR with mast cells (NARMA), non-AR with neutrophils (NARNE), and NARES and mast cells (NARESMA). All the patients were treated over 28 days with 220 MUg of nasal triamcinolone acetonide once daily. Nasal symptom score, peak inspiratory flow index, and nasal mucociliary clearance time (NMCCT) were used to evaluate treatment outcomes. RESULTS: The initial screening found 67 patients with non-AR and 82 patients with AR. At 28 days after nasal steroid treatment, all nasal symptom score, peak inspiratory flow indexes, and NMCCTs were significantly improved within each group; however, the non-AR group recorded significantly lower levels of improvement in blocked nose, rhinorrhea, sneezing, nasal itching, peak flows, and NMCCTs than the AR group. The NINAR group overall indicated lower levels of improvement than the INAR group. Among the INAR subgroups, the NARESMA, NARES, and NARMA phenotypes had similar outcome improvements, all better than the NARNE phenotype. CONCLUSION: Although both patients with non-AR and those with AR had good steroid response, the patients with non-AR had less improvement than the patients with AR. Patients with NINAR had the worst treatment outcome among the non-AR phenotypes. PMID- 26358346 TI - Quantitative sinonasal symptom assessment in an unselected pediatric population with cystic fibrosis. AB - INTRODUCTION: The aim of this study was to establish baseline sinonasal quality of life scores in an unselected pediatric population with cystic fibrosis (CF) and to test the correlation of those scores with various clinical outcome measurements. METHODS: A total of 50 consecutive children, ages 2-12 years, seen routinely in a large CF clinic were evaluated by using the Sinus and Nasal Quality of Life Survey (SN-5) tool at the time of their visit. At this time, the parent or guardian of the child was also questioned about recent episodes of sinusitis, antibiotic prescriptions for sinusitis, recent hospitalizations, and days missed from school or recreational activities due to sinonasal symptoms. CF genotype, pulmonary function, recent sinus surgeries, and computed tomography scores were established by thorough chart review. RESULTS: The average SN-5 score of this group was lower than published averages in children with baseline, preoperative, or postoperative chronic sinusitis, and demonstrated significant correlations with a visual analog scale, recent episodes of sinusitis, antibiotic prescriptions for sinusitis, and the number of days missed from school or recreational activities due to sinonasal symptoms, with a nonsignificant trend observed with previous sinus surgery. No correlations were seen with CF genotype, pulmonary function, or hospitalization days. Computed tomography results were overwhelmingly abnormal, and Lund-MacKay scores did not correlate with SN-5 scores or clinical outcome measurements. CONCLUSIONS: The SN-5 tool provides a quick, safe, and reliable qualitative metric for monitoring sinonasal symptoms in young children with CF. PMID- 26358347 TI - Skin testing versus in vitro testing in the evaluation of aeroallergy: The great debate. AB - When one examines reviews regarding diagnostic allergy testing, it generally is noted that the advantage of skin testing is that it uses testing to an end organ, is less expensive, is more sensitive, and provides immediate results, which are easily visualized by the patient. In the case of in vitro testing, it is thought to be more helpful for patients with dermographia or widespread dermatitis, is not affected by H1 or H2 antagonists, and is thought to be safer than skin testing. This may not be entirely correct because studies actually demonstrated phlebotomy to be associated with more morbidity than skin-prick testing. Other concerns regarding both tests include allergen quality, the need from proficiency testing, and the fact that these tests should be used for corroborating a diagnosis as opposed to a screening test for allergy. PMID- 26358348 TI - Objective assessment of olfaction after transsphenoidal pituitary surgery. AB - BACKGROUND: Transnasal endoscopic pituitary surgery has proven to be a safe and effective method for removing pituitary tumors. Direct and angled endoscopy at the site of dissection provides excellent visualization without external incisions. However, olfactory loss has been documented after surgical approaches to the pituitary and is accompanied by a significant detriment to quality of life. STUDY DESIGN: A prospective cohort study. METHODS: Subjects 19 years and older who were undergoing transnasal endoscopic pituitary surgery were recruited for this study. The University of Pennsylvania Smell Identification Test (UPSIT) was administered preoperatively and then at 3-4 months. Data regarding demographics, reconstructive technique, and complications were recorded. The patients had skull-base reconstruction with a Medpore implant or a vascularized nasoseptal flap. RESULTS AND DISCUSSION: A total of 33 subjects were recruited, with 18 completing the study. The mean (SEM) age was 58.2 +/- 2.4 years, with 12 females and 6 males. The majority of patients (89%) had nonfunctioning macroadenomas, and six individuals had reconstruction by using a vascularized nasoseptal flap. Matched mean (SEM) preoperative and postoperative UPSIT scores for this cohort were not significantly different (31.3 +/- 0.4 versus 30.5 +/- 0.5, respectively; p = 0.54). In addition, there was no significant difference between the mean preoperative and postoperative UPSIT scores of the patients who had nasoseptal flaps (29.4 +/- 1.1 vs. 28.6 +/- 1.3 respectively; p = 0.87). CONCLUSIONS: In the current study, pre- and postoperative UPSIT scores were not significantly different in patients who underwent endoscopic transnasal pituitary surgery. The use of a nasoseptal flap also did not adversely affect postoperative UPSIT scores. PMID- 26358349 TI - Is sex an independent prognostic factor in esthesioneuroblastoma? AB - OBJECTIVE: To determine if sex independently affects presentation and disease specific survival (DSS) in patients with esthesioneuroblastoma (ENB). STUDY DESIGN: A case-control study from the Surveillance Epidemiology and End Results (SEER) data base. METHODS: The assessment identified 611 patients in the SEER data base who were diagnosed with ENB from 1988 to 2010. Data on race, ethnicity, age at diagnosis, sex, histologic grade, radiation treatment status, and surgical treatment status of patients with ENB from 1988 to 2010 were extracted. By using tumor extension data, the modified Kadish stage of each case was determined. The modified Kadish system was able to successfully classify 547 of 611 tumors from 1988 to 2010. Histologic grade, modified Kadish stage and DSS of male patients was compared with the DSS of female patients. RESULTS: Demographic data showed that male patients presented with a significantly higher grade (p < 0.05) and a trend toward a higher stage (p = 0.08). With unmatched data, male patients had significantly worse DSS than female patients (p < 0.05). After case-matching, the difference between the DSS for male versus female patients was no longer significant. CONCLUSIONS: Male patients with ENB seemed to have significantly worse DSS at 10 years than female patients. This disparity seems to be due to higher grade and stage in male patients at presentation. After accounting for these two factors, the prognosis of male patients was not found to be significantly different from that of female patients. PMID- 26358350 TI - The effect of vibrissae on subjective and objective measures of nasal obstruction. AB - BACKGROUND: Nasal congestion and/or obstruction represents a prevalent and extensively studied problem. No published research exists that describes the impact of nasal hair (vibrissae) on nasal obstruction. OBJECTIVE: To assess the impact of nasal vibrissae on subjective and objective measurements of nasal obstruction. METHODS: In this prospective study, 30 healthy participants without nasal symptoms were assessed for baseline vibrissae density and were treated with a topical decongestant. The subjects were then asked to subjectively assess nasal breathing by using four questions from the Nasal Obstruction Symptom Evaluation instrument before undergoing rhinomanometry. Nasal vibrissae were then trimmed, and the participants repeated the subjective and objective assessments. Pre- and postintervention outcomes, including symptom scores, nasal airflow, and resistance, were compared by using statistical analysis. RESULTS: Statistically significant improvement was noted in subjects' nasal airway specific symptom scores and in objective measurements of their nasal airway. Patients with moderate or many vibrissae at baseline were noted to have greater likelihood of improvement in subjective and objective obstruction assessments than patients rated with few. CONCLUSION: In these 30 subjects, statistically significant improvement occurred in both subjective and objective assessments of nasal obstruction, particularly in patients with greater density of vibrissae. These findings support further study of the potential benefit of the reduction of vibrissae density in some patients with nasal obstruction. PMID- 26358351 TI - Impact of day of week on outcomes of endoscopic sinus surgery for chronic rhinosinusitis. AB - BACKGROUND: Outcomes for some surgical procedures are discrepantly affected by the day of the week when surgery is performed. It remains unknown whether this finding is applicable to endoscopic sinus surgery (ESS). METHODS: A retrospective analysis of a cohort from a prospective observational study of patients undergoing ESS for chronic rhinosinusitis. Primary outcome measures included major postoperative complications (epistaxis that required physician intervention, orbital injury, and cerebrospinal fluid leak) as well as Sinonasal Outcomes Test 22 (SNOT-22) and Chronic Sinusitis Survey (CSS) quality-of-life symptom scores at 3 months, 1 year, and 2 years. Associations between the day of the week when ESS was performed and outcome measures were performed when controlling for patients' clinical and demographic characteristics. RESULTS: The study population consisted of 544 patients with a 30-day major postoperative complications rate of 1.2%. There was no predilection for ESS complications by the day of the week. In comparison with ESS on a Monday, improvement in the SNOT 22 score was no different than with ESS performed on Tuesday (p = 0.800 at 3 months, p = 0.149 at 12 months, p = 0.123 at 24 months), Wednesday (p = 0.533 at 3 months, p = 0.708 at 12 months, p = 0.107 at 24 months), and Thursday (p = 0.965 at 3 months, p = 0.959 at 12 months, p = 0.501 at 24 months). No surgeries were performed on Friday. Similar results were found for improvement in CSS scores. CONCLUSION: The day of the week on which ESS was performed did not impact surgical outcomes. These results provided novel insights, which may be useful for preoperative discussions with patients and scheduling of ESS. PMID- 26358352 TI - Two- versus four-handed techniques for endonasal resection of orbital apex tumors. AB - BACKGROUND: Open versus endonasal resection of orbital apex (OA) tumors is generally based on tumor size, location, and pathology. For endonasal resection, two- and four-handed techniques have been reported, but whether one technique is more optimal based on these tumor features has not been evaluated. OBJECTIVE: To determine whether two- versus four-handed techniques result in better outcomes after endoscopic resection of OA tumors, and whether either technique is better suited for intra- versus extraconal location and for benign versus malignant pathology. METHODS: A retrospective review of all expanded endonasal approaches for OA tumors was performed at a single institution from 2009 to 2013. A PubMed database search was also performed to review series published on endonasal OA tumor resection. Across all the cases reviewed, the following data were recorded: two- versus four-handed techniques, intra- versus extraconal tumor location, and benign versus malignant pathology. The relationship between these variables and resection extent was analyzed by the Fisher exact test. Postoperative visual status and complications were also reviewed. RESULTS: Ten cases from the institution and 94 cases from 17 publications were reviewed. Both two- and four handed techniques were used to resect extra- and intraconal OA tumors, for both benign and malignant pathology. Four-handed techniques included a purely endonasal approach and a combined endonasal-orbital approach. On univariate analysis, the strongest predictor of complete resection was benign pathology (p = 0.005). No significant difference was found between the extent of resection and a two- versus a four-handed technique. Visual status was improved or unchanged in 94% of cases, and other complications were rare. CONCLUSION: Benign tumors that involve the medial extraconal and posterior inferomedial intraconal OA can be treated by either two- or four-handed endonasal techniques. Selecting two- versus four-handed techniques and endonasal versus endonasal-orbital four-handed techniques depends mainly on surgeons' experience. Endonasal approaches for malignant OA tumors are less likely to result in complete resection. PMID- 26358353 TI - Attitudes on and usage of balloon catheter technology in rhinology: A survey of the American Rhinologic Society. AB - INTRODUCTION: Use of balloon catheter dilation in the management of paranasal sinus diseases, including chronic rhinosinusitis (CRS) and recurrent acute rhinosinusitis, remains controversial. In an effort to gain some clarity about its evolving role, we surveyed members of the American Rhinologic Society (ARS). METHOD: Online survey. RESULTS: ARS Members were sent an invitation by e-mail to participate in an online, anonymous 23-item survey. A total of 231 participants completed the survey, for an overall response rate of 25%. Balloon catheter technology (BCT) played no role in the practices of one-third of all the respondents. Of those who did use BCT, more than 50% performed only 1-4 cases per month on average. This did not differ significantly with practice type (p = 0.2988). The overall use of BCT differed between types of practices with those in private practice reporting greater use of the technology for maxillary and sphenoid sinuses (p = 0.0003 and p = 0.0073, respectively). Participants in private practice appeared significantly more impressed with the results of BCT when compared with those in academia (p = 0.0005) and also thought that patients were more satisfied (p = 0.0002). Opinions toward the strength of available evidence also differed significantly between the two groups (p = 0.0007). Thirty two respondents had experienced a complication with BCT, although the majority of these did not require any intervention. CONCLUSIONS: ARS members surveyed used BCT infrequently in their practices. Attitudes on the role of this technology in CRS management differed between academic and private practitioners, but, despite this, the volume of reported BCT use was the same. Surgeons are more accepting of the technology now compared with 5 years ago, and many of them believe that their use of BCT will increase in the future. PMID- 26358354 TI - Quantification of maxillary sinus accessibility via a middle meatal antrostomy. AB - OBJECTIVE: To quantify maxillary sinus volume and mucosal surface area (SA) that is accessible endoscopically via a middle meatal antrostomy and to explore the financial implications of using multiple disposable instruments for this procedure. METHODS: Eight cadaver maxillary sinuses configured with image guidance software were evaluated. In each sinus, a standard middle meatal antrostomy was created, through which curved microdebriders of 15, 40, 70, and 120 degrees were placed. The SA and volume of the region accessible by each microdebrider tip was calculated. RESULTS: Mean maxillary sinus volume was 16.5 +/- 2.5 cm(3) and mean SA was 31.0 +/- 2.3 cm(2). The 15, 40, 70 and 120 degrees microdebriders accessed an average of 10, 25, 41, and 66%, respectively, of the SA, and of 2, 9, 17, and 36%, respectively, of the volume. There was a trend toward improved accessibility of the superior half versus the inferior half of the maxillary sinus. When instruments of different degrees were combined to maximize accessibility, 81% of the SA of the sinus could be accessed. CONCLUSIONS: Microdebriders with increasing curvatures allowed for greater access of the maxillary sinus mucosa through an middle meatal antrostomy. No single microdebrider curvature or combination of curvatures reached the entirety of the maxillary sinus wall. Knowledge about the area of reach for these blades can lead to lower per procedure costs. PMID- 26358355 TI - Outside-In Frontal Drill-Out: How I Do It. AB - BACKGROUND: The Draf 3 frontal sinusotomy, or modified Lothrop procedure has been used to treat recalcitrant rhinosinusitis, frontal sinus mucocoeles or to provide access for cerebrospinal fluid leaks, frontoethmoid fractures, frontal sinus tumors and skull base tumors. OBJECTIVE: To describe authors approach to the "Outside-In Frontal Drill-Out". METHODS: Descriptive. RESULTS: The "Outside-In" frontal drill-out is an approach that emphasizes the early identification of the first olfactory neuron, maximization of bone removal, and preservation of the posterior table mucosa. CONCLUSION: The advantages of this approach are it provides unobstructed view and identifies anatomic limits early, bone removal is fast and efficient; it is safe, and it is a robust technique based upon fixed anatomic landmarks. PMID- 26358356 TI - Otolaryngology: Medical Treatment of Traumatic Anosmia. PMID- 26358357 TI - Childhood maltreatment, pubertal development, HPA axis functioning, and psychosocial outcomes: An integrative biopsychosocial model. AB - The timing and pace of pubertal development has been associated with psychosocial functioning, with pubertal variables represented both as predictors (e.g., earlier puberty linked with poor outcomes) and as sequelae (e.g., early stress linked with earlier puberty). However, the literature has largely not tested mediational models or prospective mechanisms of associations between puberty and psychosocial variables. In a longitudinal study including 454 youth followed over four timepoints (mean ages 10-18), structural equation modeling tested a hypothesized path from childhood maltreatment to cortisol (Time 1) to pubertal stage (Time 2), and psychosocial outcomes (Times 3 and 4). There was not support for the full hypothesized pathway in either gender. However, for boys, maltreatment was associated with attenuated cortisol, and more pubertal change predicted subsequent delinquency. For girls, cortisol predicted more pubertal change which then predicted substance use. This study demonstrates links between HPA axis function, pubertal development, and risky outcomes. PMID- 26358360 TI - [Business intelligence in radiology. Challenges and opportunities]. AB - Due to economic pressures and need for higher transparency, a ubiquitous availability of administrative information is needed. Therefore radiology managers should consider implementing business intelligence (BI) solutions. BI is defined as a systemic approach to support decision-making in business administration. It is an important part of the overall strategy of an organization. Implementation and operation is initially associated with costs and for a successful launch important prerequisites must be fulfilled. First, a suitable product must be selected, followed by the technical and organizational implementation. After consideration of the type of data to be collected and a system of key performance indicators must be established. BI replaces classic retrospective business reporting with multidimensional and multifactorial analyses, real-time monitoring, and predictive analyses. The benefits of BI include the rapid availability of important information and the depth of possible data analysis. The simple and intuitive use of modern BI applications by the users themselves (!) combined with a continuous availability of information is the key to success. Professional BI will be an important part of management in radiology in the future. PMID- 26358361 TI - [Vertebroplasty--state of the art]. AB - BACKGROUND: Percutaneous vertebroplasty (PVP) using PMMA (polymethyl methacrylate) was first described in 1987 by Gallibert and Deramond for the treatment of vertebral body instability in patients with aggressive forms of vertebral hemangioma. Other types of painful osteolytic bone lesions, such as osteoporotic vertebral fractures and vertebral metastasis are in the meantime more commonly treated using this method. METHODICAL INNOVATIONS: Within the last few years, this technique has become widely accepted and it is proposed for osteolytic bone lesions in areas that are more difficult to approach surgically, e.g., the pelvis and sacrum. EFFICACY: Rapid pain relief and resulting stability have conferred an important role upon osteoplasty especially in palliative tumor treatment for patients with shortened expected life spans. In addition, combined treatment of painful osteolytic metastases with image-guided thermoablation and percutaneous cement injection has been shown to be a safe palliative modality in the therapy of nonresectable tumors. PMID- 26358359 TI - CARD14 alterations in Tunisian patients with psoriasis and further characterization in European cohorts. AB - BACKGROUND: Rare highly penetrant gain-of-function mutations in caspase recruitment domain family, member 14 (CARD14) can lead to psoriasis, a chronic inflammatory disease of the skin and other organs. OBJECTIVES: To investigate the contribution of rare CARD14 variants to psoriasis in the Tunisian population and to expand knowledge of CARD14 variants in the European population. METHODS: CARD14 coding exons were resequenced in patients with psoriasis and controls from Tunisia and Europe, including 16 European cases with generalized pustular psoriasis (GPP). Novel variants were evaluated for their effect on nuclear factor (NF)-kappaB signalling. RESULTS: Rare variants in CARD14 were significantly enriched in Tunisian cases compared with controls. Three were collectively found in 5% of Tunisian cases, and all affected the N-terminal region of the protein harbouring its caspase recruitment domain or coiled-coil domain. These variants were c.349G>A (p.Gly117Ser), c.205C>T (p.Arg69Trp) and c.589G>A (p.Glu197Lys). c.589G>A (p.Glu197Lys) led to upregulation of NF-kappaB activity in a similar manner to that of previously described psoriasis-associated mutations. p.Arg69Trp led to sevenfold downregulation of NF-kappaB activity. One Tunisian case harboured a c.1356+5G>A splice alteration that is predicted to lead to loss of exon 9, which encodes part of the coiled-coil domain. No cases of GPP harboured an interleukin-36RN mutation, but one of 16 cases of GPP with a family history of psoriasis vulgaris harboured a c.1805C>T (p.Ser602Leu) mutation in CARD14. CONCLUSIONS: These observations provide further insights into the genetic basis of psoriasis in the Tunisian population and provide functional information on novel CARD14 variants seen in cases from Tunisia and other populations. PMID- 26358358 TI - Effect of Fructose on Established Lipid Targets: A Systematic Review and Meta Analysis of Controlled Feeding Trials. AB - BACKGROUND: Debate over the role of fructose in mediating cardiovascular risk remains active. To update the evidence on the effect of fructose on established therapeutic lipid targets for cardiovascular disease (low-density lipoprotein cholesterol [LDL]-C, apolipoprotein B, non-high-density lipoprotein cholesterol [HDL-C]), and metabolic syndrome (triglycerides and HDL-C), we conducted a systematic review and meta-analysis of controlled feeding trials. METHODS AND RESULTS: MEDLINE, EMBASE, CINHAL, and the Cochrane Library were searched through July 7, 2015 for controlled feeding trials with follow-up >=7 days, which investigated the effect of oral fructose compared to a control carbohydrate on lipids (LDL-C, apolipoprotein B, non-HDL-C, triglycerides, and HDL-C) in participants of all health backgrounds. Two independent reviewers extracted relevant data. Data were pooled using random effects models and expressed as mean difference with 95% CI. Interstudy heterogeneity was assessed (Cochran Q statistic) and quantified (I(2) statistic). Eligibility criteria were met by 51 isocaloric trials (n=943), in which fructose was provided in isocaloric exchange for other carbohydrates, and 8 hypercaloric trials (n=125), in which fructose supplemented control diets with excess calories compared to the control diets alone without the excess calories. Fructose had no effect on LDL-C, non-HDL-C, apolipoprotein B, triglycerides, or HDL-C in isocaloric trials. However, in hypercaloric trials, fructose increased apolipoprotein B (n=2 trials; mean difference = 0.18 mmol/L; 95% CI: 0.05, 0.30; P=0.005) and triglycerides (n=8 trials; mean difference = 0.26 mmol/L; 95% CI: 0.11, 0.41; P<0.001). The study is limited by small sample sizes, limited follow-up, and low quality scores of the included trials. CONCLUSIONS: Pooled analyses showed that fructose only had an adverse effect on established lipid targets when added to existing diets so as to provide excess calories (+21% to 35% energy). When isocalorically exchanged for other carbohydrates, fructose had no adverse effects on blood lipids. More trials that are larger, longer, and higher quality are required. CLINICAL TRIALS REGISTRATION: URL: https://www.clinicaltrials.gov/. Unique Identifier: NCT01363791. PMID- 26358362 TI - Oncoplastic reduction mammoplasty for breast cancer in women with macromastia: Oncological long-term outcomes. AB - OBJECTIVE: To evaluate the long-term results of tumorectomy and concomitant bilateral oncoplastic reduction mammoplasty (ORM) for early stage breast cancer patients with macromastia in terms of local disease control and long-term oncological results. PATIENTS AND METHOD: Data of 82 patients with macromastia undergoing ORM for breast cancer between 1996 and 2011 were retrospectively examined and evaluated with regard to oncological results. RESULTS: The median age was 50 years. The median follow-up was 121 months (range 28-212 months). The median breast volume was 1402 cm3 and the median weight of excised breast material was 679 g. The median surgical margin was 16 mm. Ten-year local recurrence rate was 8.7%. The 10-year overall survival rate was 82.2% and the disease-free survival rate was 73.2%. Early and late complication rates were 12.2% and 14.6%, respectively. CONCLUSIONS: From the standpoint of local disease control and long-term observation, ORM can be considered a very safe and acceptable treatment for early stage breast cancer in women with macromastia. PMID- 26358363 TI - Xq21.31-q21.32 duplication underlies intellectual disability in a large family with five affected males. AB - X-linked intellectual disability is the most common form of neurological disorder in male and accounts for 5-10% of incidence in the population. Copy number variants (CNVs) have been studied extensively to identify genomic regions responsible for neurological disorders. Array CGH and SNP genotyping have identified several CNVs on X-chromosome in patients with X-linked intellectual disability. We genotyped 2.5 million SNPs in 10 individuals of a 4 generation family segregating X-linked intellectual disability using Illumina Infinium BeadChip assay. Whole genome genotyping data analysis identified a single duplication of 3.95 Mb on X-chromosome in all five affected male individuals. This CNV is inherited from a healthy mother. All five affected individuals manifest moderate to severe intellectual disability, seizures and behavioral abnormalities. X-chromosome inactivation analysis showed that X-chromosome of the mother with duplication is completely inactivated which has also been found in daughters. PMID- 26358365 TI - The delicate balance of macrophages in colorectal cancer; their role in tumour development and therapeutic potential. AB - Most tumours are heavily infiltrated by immune cells. This has been correlated with either a good or a bad patient prognosis, depending on the (sub) type of immune cells. Macrophages represent one of the most prominent leukocyte populations in the majority of tumours. Functions of macrophages range from cytotoxicity, to stimulation of tumour growth by secretion of cytokines, growth and angiogenic factors, or suppressing immune responses. In most tumours macrophages are described as cells with immune suppressing, and wound healing properties, which aids tumour development. Yet, increasing evidence shows that macrophages are potent inhibitors of tumour growth in colorectal cancer. Macrophages in this respect show high plasticity. The presence of high macrophage numbers in the tumour may therefore become advantageous, if cells can be reprogrammed from tumour promoting macrophages into potent effector cells. Enhancing cytotoxic properties of macrophages by microbial products, pro inflammatory cytokines or monoclonal antibody therapy are promising possibilities, and are currently tested in clinical trials. PMID- 26358366 TI - Glucocorticoid dexamethasone down-regulates basal and vitamin D3 induced cathelicidin expression in human monocytes and bronchial epithelial cell line. AB - Glucocorticoids (GCs) have been extensively used as the mainstream treatment for chronic inflammatory disorders. The persistent use of steroids in the past decades and the association with secondary infections warrants for detailed investigation into their effects on the innate immune system and the therapeutic outcome. In this study, we analyse the effect of GCs on antimicrobial polypeptide (AMP) expression. We hypothesize that GC related side effects, including secondary infections are a result of compromised innate immune responses. Here, we show that treatment with dexamethasone (Dex) inhibits basal mRNA expression of the following AMPs; human cathelicidin, human beta defensin 1, lysozyme and secretory leukocyte peptidase 1 in the THP-1 monocytic cell-line (THP-1 monocytes). Furthermore, pre-treatment with Dex inhibits vitamin D3 induced cathelicidin expression in THP-1 monocytes, primary monocytes and in the human bronchial epithelial cell line BCi NS 1.1. We also demonstrate that treatment with the glucocorticoid receptor (GR) inhibitor RU486 counteracts Dex mediated down-regulation of basal and vitamin D3 induced cathelicidin expression in THP-1 monocytes. Moreover, we confirmed the anti-inflammatory effect of Dex. Pre treatment with Dex inhibits dsRNA mimic poly IC induction of the inflammatory chemokine IP10 (CXCL10) and cytokine IL1B mRNA expression in THP-1 monocytes. These results suggest that GCs inhibit innate immune responses, in addition to exerting beneficial anti-inflammatory effects. PMID- 26358364 TI - Menopausal hormone therapy and sleep-disordered breathing: evidence for a healthy user bias. AB - PURPOSE: Observational studies suggest that menopausal hormone therapy protects against sleep-disordered breathing, but such findings may be biased by a "healthy user effect." When the Women's Health Initiative Study reported in 2002 that estrogen-progestin therapy increases heart disease risk, many women discontinued hormone therapy. We investigate healthy user bias in the association of hormone therapy with sleep-disordered breathing in the Sleep in Midlife Women Study. METHODS: A total of 228 women aged 38 to 62 years were recruited from the Wisconsin Sleep Cohort Study. They underwent polysomnography to measure apnea hypopnea index, at home semiannually from 1997 to 2006, and in the sleep laboratory every four years (n = 1828 studies). Hormone therapy was recorded monthly. Linear models with empirical standard errors regressed logarithm of apnea-hypopnea index on hormone use with a pre- or post-July 2002 interaction, adjusting for menopause and age. RESULTS: The association of hormone therapy and sleep-disordered breathing was heterogeneous (P < .01); apnea-hypopnea index among users was 15% lower in the early period (95% confidence interval, -27% to 1%), but similar to nonusers in the late. CONCLUSIONS: Hormone therapy was negatively associated with sleep-disordered breathing only until the Women's Health Initiative results were publicized. Hormone therapy may have been a marker for healthfulness in the early period, creating a spurious association with sleep disordered breathing. PMID- 26358367 TI - Hyperinsulinemia shifted energy supply from glucose to ketone bodies in early nonalcoholic steatohepatitis from high-fat high-sucrose diet induced Bama minipigs. AB - The minipig can serve as a good pharmacological model for human subjects. However, the long-term pathogenesis of high-calorie diet-induced metabolic syndromes, including NASH, has not been well described in minipigs. We examined the development of metabolic syndromes in Bama minipigs that were fed a high-fat, high-sucrose diet (HFHSD) for 23 months, by using histology and serum biochemistry and by profiling the gene expression patterns in the livers of HFHSD pigs compared to controls. The pathology findings revealed microvesicular steatosis, iron overload, arachidonic acid synthesis, lipid peroxidation, reduced antioxidant capacity, increased cellular damage, and inflammation in the liver. RNA-seq analysis revealed that 164 genes were differentially expressed between the livers of the HFHSD and control groups. The pathogenesis of early-stage NASH was characterized by hyperinsulinemia and by de novo synthesis of fatty acids and nascent triglycerides, which were deposited as lipid droplets in hepatocytes. Hyperinsulinemia shifted the energy supply from glucose to ketone bodies, and the high ketone body concentration induced the overexpression of cytochrome P450 2E1 (CYP2E1). The iron overload, CYP2E1 and alcohol dehydrogenase 4 overexpression promoted reactive oxygen species (ROS) production, which resulted in arachidonic and linoleic acid peroxidation and, in turn, led to malondialdehyde production and a cellular response to ROS-mediated DNA damage. PMID- 26358368 TI - Synergistic effects of diet and exercise on hippocampal function in chronically stressed mice. AB - Severe chronic stress can have a profoundly negative impact on the brain, affecting plasticity, neurogenesis, memory and mood. On the other hand, there are factors that upregulate neurogenesis, which include dietary antioxidants and physical activity. These factors are associated with biochemical processes that are also altered in age-related cognitive decline and dementia, such as neurotrophin expression, oxidative stress and inflammation. We exposed mice to an unpredictable series of stressors or left them undisturbed (controls). Subsets of stressed and control mice were concurrently given (1) no additional treatment, (2) a complex dietary supplement (CDS) designed to ameliorate inflammation, oxidative stress, mitochondrial dysfunction, insulin resistance and membrane integrity, (3) a running wheel in each of their home cages that permitted them to exercise, or (4) both the CDS and the running wheel for exercise. Four weeks of unpredictable stress reduced the animals' preference for saccharin, increased their adrenal weights and abolished the exercise-induced upregulation of neurogenesis that was observed in non-stressed animals. Unexpectedly, stress did not reduce hippocampal size, brain-derived neurotrophic factor (BDNF), or neurogenesis. The combination of dietary supplementation and exercise had multiple beneficial effects, as reflected in the number of doublecortin (DCX) positive immature neurons in the dentate gyrus (DG), the sectional area of the DG and hippocampal CA1, as well as increased hippocampal BDNF messenger ribonucleic acid (mRNA) and serum vascular endothelial growth factor (VEGF) levels. In contrast, these benefits were not observed in chronically stressed animals exposed to either dietary supplementation or exercise alone. These findings could have important clinical implications for those suffering from chronic stress related disorders such as major depression. PMID- 26358369 TI - Targeting Bacterial Cell Wall Peptidoglycan Synthesis by Inhibition of Glycosyltransferase Activity. AB - Synthesis of bacterial cell wall peptidoglycan requires glycosyltransferase enzymes that transfer the disaccharide-peptide from lipid II onto the growing glycan chain. The polymerization of the glycan chain precedes cross-linking by penicillin-binding proteins and is essential for growth for key bacterial pathogens. As such, bacterial cell wall glycosyltransferases are an attractive target for antibiotic drug discovery. However, significant challenges to the development of inhibitors for these targets include the development of suitable assays and chemical matter that is suited to the nature of the binding site. We developed glycosyltransferase enzymatic activity and binding assays using the natural products moenomycin and vancomycin as model inhibitors. In addition, we designed a library of disaccharide compounds based on the minimum moenomycin fragment with peptidoglycan glycosyltransferase inhibitory activity and based on a more drug-like and synthetically versatile disaccharide building block. A subset of these disaccharide compounds bound and inhibited the glycosyltransferase enzymes, and these compounds could serve as chemical entry points for antibiotic development. PMID- 26358370 TI - Removal of Phosphorus by Hemodialysis. AB - The control of serum phosphorus by dialysis is made difficult by the fact that intradialytic blood levels tend to be low, and because phosphorus is removed almost exclusively from the plasma during its passage through the dialyzer. The most practical way to increase phosphorus removal is to extend dialysis time, although attention to dialysis efficiency (surface area, advanced membrane, and higher blood and dialysate flow rates) also plays a role. Benefits of hemodiafiltration in helping control serum phosphorus have been claimed, but not found in all studies. Because serum phosphorus levels tend to plateau during the later parts of a dialysis session, extending weekly dialysis time is of greater benefit for phosphorus removal than for urea removal. Increasing dialysis frequency also probably has a small benefit. It appears that 18-30 hours of dialysis per week are required to obviate the need for phosphorus binders. Several promising models of phosphorus kinetics are under development. These may help predict the change in treatment on serum phosphorus levels, but their ability to do so has not yet been critically assessed. PMID- 26358371 TI - Superficial desmoid tumors: MRI and ultrasound imaging characteristics. AB - OBJECTIVES: To describe the imaging characteristics of superficial desmoid tumors using magnetic resonance imaging (MRI) and high-resolution sonography (HRUS). METHODS: We retrospectively examined 18 patients (12 females and 6 males) with histologically proven superficial desmoids. Fourteen patients received MRI examinations, while 12 patients were examined with HRUS. The lesions were assessed with regard to location, muscular fascia involvement, and spread into the subcutaneous fatty tissue septa, adjacent muscle, and bone. In addition, size, shape, signal intensity/echogenicity relative to muscle, amount of collagen components, Doppler vascularity on HRUS and the degree of contrast enhancement in MRI were evaluated. RESULTS: Altogether there were 20 subcutaneous lesions: six involved the chest wall and the breasts, five the hip, four each the shoulder and the flank, and one the abdominal wall. All but three lesions showed a stellar type configuration with multiple irregular sun-burst-like extensions along the fascial planes and septa of the subcutaneous fat tissue. The extensions spread away from the main tumor focus, and in nine lesions, these extensions reached the cutis. The remaining three lesions had a spindle shape and also presented extensions along the fascial planes. Another imaging feature in all lesions was the presence of variable amounts of collagen components, with typical low signal on MRI and/or fibrillar hyperechoic appearance in HRUS. CONCLUSION: The distinctive imaging features of collagen components associated with sun-burst like extensions in our sample of superficial desmoids are valuable diagnostic clues in the challenging non-invasive differential diagnosis of these tumors. PMID- 26358372 TI - A retrospective analysis of computed tomography findings in patients with pulmonary complications after allogeneic hematopoietic stem cell transplantation. AB - OBJECTIVE: The purpose of this study was to review the high-resolution computed tomography (CT) findings in patients with pulmonary complications after allogeneic hematopoietic stem cell transplantation (HSCT), and to evaluate the relationship between CT findings and clinical outcomes. PATIENTS AND METHODS: We collected the clinical data in 96 consecutive patients who underwent CT scan for pulmonary complications after allogeneic HSCT and analyzed the relationships among these clinical characteristics, CT findings and clinical responses. Radiologists who were blinded to clinical information evaluated the CT findings. RESULTS: In multivariate analyses, the presence of chronic graft-versus-host disease (GVHD) and non-segmental multiple consolidations were significantly associated with a poor response to antimicrobial therapies, and the disease risk was significantly associated with a poor corticosteroid response. In addition, the existence of cavity formation and pleural effusion were significantly associated with a fatal prognosis. Twenty-five patients underwent bronchoscopic examination and 4 of them also underwent transbronchial lung biopsy (TBLB), but diagnostic information was not obtained in 15 patients. There was no significant association between specific CT findings and the diagnosis based on bronchoscopic examination. CONCLUSIONS: No specific CT finding was identified as a predictor for either an antimicrobial response or for a corticosteroid response in this study. The presence of cavity formation and pleural effusion may predict a poor prognosis. PMID- 26358374 TI - The mechanism of excited-state proton transfer in 1-naphthol-piperidine clusters. AB - The geometries of 1-naphthol-(piperidine)n (1-NpOH-(Pip)n) (n = 0-3) clusters have been calculated by using density functional theory (DFT) and time-dependent density functional theory (TD-DFT) methods to investigate excited-state proton transfer (ESPT) in the low-lying singlet excited states, La and Lb. For the n = 1 cluster, no PT structure was found in Lb and La as well as the ground state, S0. For n = 2, optically accessible Lb from S0 shows the PT structure. We therefore concluded that the threshold size of ESPT is n = 2, which is consistent with previous experimental results. ESPT in 1-NpOH-(Pip)n is simply triggered by optical excitation to Lb. It is essentially different from the 1-NpOH-(NH3)n cluster in which an internal conversion process is required to promote ESPT. From the calculated structures, the importance of the solvation of the pi-ring is strongly suggested rather than the proton affinity in ESPT. PMID- 26358373 TI - Combinatorial treatment using targeted MEK and SRC inhibitors synergistically abrogates tumor cell growth and induces mesenchymal-epithelial transition in non small-cell lung carcinoma. AB - Oncogenesis in non-small cell lung cancer (NSCLC) is regulated by a complex signal transduction network. Single-agent targeted therapy fails frequently due to treatment insensitivity and acquired resistance. In this study, we demonstrate that co-inhibition of the MAPK and SRC pathways using a PD0325901 and Saracatinib kinase inhibitor combination can abrogate tumor growth in NSCLC. PD0325901/Saracatinib at 0.25:1 combination was screened against a panel of 28 NSCLC cell lines and 68% of cell lines were found to be sensitive (IC50 < 2 MUM) to this combination. In Snail1 positive NSCLC lines, the drug combination complementarily enhanced mesenchymal-epithelial transition (MET), increasing both E-cadherin and Plakoglobin expression, and reducing Snail1, FAK and PXN expression. In addition, the drug combination abrogated cell migration and matrigel invasion. The co-inhibition of MAPK and SRC induced strong G1/G0 cell cycle arrest in the NSCLC lines, inhibited anchorage independent growth and delayed tumor growth in H460 and H358 mouse xenografts. These data provide rationale for further investigating the combination of MAPK and SRC pathway inhibitors in advanced stage NSCLC. PMID- 26358375 TI - Erythrocytapheresis versus phlebotomy in the maintenance treatment of HFE hemochromatosis patients: results from a randomized crossover trial. AB - BACKGROUND: Phlebotomy is standard maintenance treatment of patients with hereditary hemochromatosis (HH). Erythrocytapheresis, which selectively removes red blood cells, provides a new, potentially more effective treatment option. Our aim was to evaluate the effectiveness of erythrocytapheresis over phlebotomy for maintenance therapy in patients with HH. STUDY DESIGN AND METHODS: We conducted a two-treatment-arms, randomized, crossover clinical trial, involving 46 patients, treated for 1 year with either erythrocytapheresis or phlebotomy to keep the ferritin level at not more than 50 ug/L. After 1 year, patients were switched to the other treatment modality. Primary endpoint was the number of treatment procedures per treatment year. Secondary endpoints were intertreatment intervals, several aspects of health-related quality of life, costs, and patient discomfort as well as preference for one of both treatments. RESULTS: The mean number of required treatment procedures per treatment year was significantly higher using phlebotomy versus erythrocytapheresis (3.3 vs. 1.9; mean difference, 1.4; 95% confidence interval, 1.1-1.7). The median intertreatment time was 2.3 times longer for erythrocytapheresis. There was no significant difference in overall health assessed by SF-36 and EQ-5D, respectively, between both treatments arms. The number of self-reported swollen joints was significantly higher during phlebotomy treatment. The mean treatment costs of one treatment year were 235? for phlebotomy versus 511? for erythrocytapheresis. Eighty percent of patients preferred erythrocytapheresis as treatment method. CONCLUSION: Erythrocytapheresis significantly reduced the number of treatment procedures per treatment year, although the mean treatment costs per year are higher in our health care system. It is the preferred treatment for the majority of patients. PMID- 26358377 TI - Royal Society of Chemistry Awards 2015. PMID- 26358376 TI - Alcohol use in the Pacific region: Results from the STEPwise approach to surveillance, Global School-Based Student Health Survey and Youth Risk Behavior Surveillance System. AB - INTRODUCTION AND AIMS: Alcohol use is a leading risk factor for disease and injury in Pacific Island countries and territories (PICT). This paper examines drinking patterns across 20 PICTs. DESIGN AND METHODS: We synthesised published data from the STEPwise approach to surveillance or similar surveys for adults 25 64 years, and from the Global School-Based Student Health surveys and Youth Risk Behavior Surveillance System (YRBSS) for youth. We examined current and heavy drinking, and for adults also frequency of consumption. Using YRBSS, we studied trends in youth alcohol use in US-affiliated PICTs between 2001 and 2013. RESULTS: Alcohol consumption in adults and youth varied considerably across PICTs. In eight PICT populations, over 60% of male adults were current drinkers. Male adults consumed alcohol more frequently and engaged in heavy drinking more than female adults. Similar gender differences occurred in current and heavy drinking among youth. Across 10 PICTs, current drinking prevalence in males 13-15 years ranged from 10% to over 40%. Declines in alcohol use among grade 9-12 students were observed in YRBSS, although the magnitude differed by island and sex. DISCUSSION AND CONCLUSIONS: Alcohol consumption varies widely between PICTs. There are marked gender differences in use and abstention. There is scope in PICTs for implementation of best practice strategies to reduce alcohol-related harm. These need to be gender responsive and cognisant of concerning patterns of youth drinking. Strengthening surveillance of alcohol use and its consequences is vital to inform and monitor the impact of national and regional policies. [Kessaram T, McKenzie J, Girin N, Roth A, Vivili P, Williams G, Hoy D. Alcohol use in the Pacific region: Results from the STEPwise approach to surveillance, Global School-Based Student Health Survey and Youth Risk Behavior Surveillance System. Drug Alcohol Rev 2016;35:412-423]. PMID- 26358378 TI - Pathways and trajectories linking housing instability and poor health among low income women experiencing intimate partner violence (IPV): Toward a conceptual framework. AB - We used grounded theory to understand pathways and trajectories to housing instability (HI) and poor health among low-income women with experiences of intimate partner violence (IPV). We conducted in-depth interviews during 2010-11 with forty-one women (ages 18-45 years) living in Ontario, Canada. All women reported depressive symptoms in combination with other health problems. In addition to the direct pathway of IPV to poor health, thematic analysis revealed an indirect multi-tiered pathway with complex trajectories among IPV, HI, and poor health. These trajectories included material HI (homelessness, high mobility, evictions, problems paying rent, hiding, and landlord discrimination), psychological HI (feeling unsafe, low self-esteem, and poor control), and social trajectories (financial problems, loss of employment, income, or social networks, and leaving school). These trajectories elevated stress and decreased self-care (unhealthy behaviors, substance abuse, and reduced medical compliance) and exacerbated poor health already compromised by IPV. Depending on her specific context, each woman experienced these pathways and trajectories differently. Moreover, the women's experiences differed across three time periods: before, immediately after, and long after leaving an abusive relationship. Finally, we found that for these women, achieving stable housing was crucial for stabilizing their health. PMID- 26358379 TI - Everything Is Connected. PMID- 26358380 TI - Star Trek Publishing. PMID- 26358383 TI - Collagen Turnover in Wound Repair--A Macrophage Connection. AB - In this issue, Rohani et al. (2015) report on the role of macrophage-derived stromelysin-2 (matrix metalloproteinase (MMP)-10) in promoting the turnover of extracellular matrix (ECM) during cutaneous wound repair. They provide evidence that MMP-10 specifically enhances collagenolytic activity of murine MMP-13 produced by M2-like macrophages. These results emphasize the important role of macrophage-derived MMP-10 in regulating tissue remodeling and scar formation during wound healing. PMID- 26358384 TI - Playing Polo-Like Kinase in NRAS-Mutant Melanoma. AB - NRAS-mutant melanomas are extremely aggressive and highly resistant to currently available therapeutic modalities. Hence, new targets and therapeutic strategies for NRAS-driven melanomas are needed. As blocking NRAS directly has not been possible thus far, targeting downstream NRAS effectors, such as MAPK/ERK kinase (MEK), is being evaluated as an alternative therapeutic approach. However, blocking this pathway alone has limited efficacy. In this issue, Posch et al. report on a combination approach co-targeting polo-like kinase 1 and MEK in NRAS mutant melanomas. This combination triggers a dual blockade of the cell cycle machinery, leading to apoptosis, and providing a new strategy to treat NRAS mutant melanoma. PMID- 26358385 TI - The Broad Stroke of Hsp90 Inhibitors: Painting over the RAF Inhibitor Paradox. AB - The novel Hsp90 inhibitor XL888 is undergoing clinical investigation for use in conjunction with the rapidly accelerated fibrosarcoma (RAF) kinase inhibitor vemurafenib to treat unresectable melanoma. The addition of XL888 to current regimens may serve an additional purpose by blocking the RAF inhibitor paradox. Such activity could reduce adverse events in patients and provide a biomarker for the successful inhibition of Hsp90 target proteins. PMID- 26358386 TI - Superior Suppressive Capacity of Skin Tregs Compared with Lung Tregs in a Model of Epicutaneous Priming. AB - We have previously shown that T helper type 2 (Th2)-polarized airway inflammation can facilitate priming to new antigens in the lungs, which we called "collateral priming". To investigate whether allergic skin inflammation can also facilitate priming toward new antigens, we developed an allergic skin inflammation model based on an allergic lung inflammation model. Mice were sensitized intraperitoneally toward the primary antigen, ovalbumin. Challenge was subsequently performed intranasally or epicutaneously with ovalbumin and a secondary antigen, keyhole limpet hemocyanin (KLH). Re-challenge consisted of local application of either antigen alone. Analysis of KLH-specific antibody responses, KLH-specific cytokines, and local inflammation demonstrated tolerance induction toward the secondary antigen in the skin, whereas in the lung priming had occurred. Flow-cytometric analysis revealed increased numbers of regulatory T cells (Tregs), increased cytotoxic T lymphocyte antigen-4 (CTLA-4) expression, and an enhanced suppressive capacity of Tregs from skin-draining lymph nodes when compared with Tregs from the lung-draining lymph nodes. Furthermore, depletion of Tregs resulted in restoration of collateral priming in the skin. These results demonstrate crucial local differences between the Treg function in the skin and lung to repetitive antigen exposure, which can decisively influence the immune response toward new antigens. PMID- 26358388 TI - Cells to Surgery Quiz: October 2015. PMID- 26358387 TI - Acellular Hydrogels for Regenerative Burn Wound Healing: Translation from a Porcine Model. AB - Currently available skin grafts and skin substitutes for healing following third degree burn injuries are fraught with complications, often resulting in long-term physical and psychological sequelae. Synthetic treatment that can promote wound healing in a regenerative manner would provide an off-the-shelf, non-immunogenic strategy to improve clinical care of severe burn wounds. Here, we demonstrate the vulnerary efficacy and accelerated healing mechanism of a dextran-based hydrogel in a third-degree porcine burn model. The model was optimized to allow examination of the hydrogel treatment for clinical translation and its regenerative response mechanisms. Hydrogel treatment accelerated third-degree burn wound healing by rapid wound closure, improved re-epithelialization, enhanced extracellular matrix remodeling, and greater nerve reinnervation, compared with the dressing-treated group. These effects appear to be mediated through the ability of the hydrogel to facilitate a rapid but brief initial inflammatory response that coherently stimulates neovascularization within the granulation tissue during the first week of treatment, followed by an efficient vascular regression to promote a regenerative healing process. Our results suggest that the dextran-based hydrogels may substantially improve healing quality and reduce skin grafting incidents and thus pave the way for clinical studies to improve the care of severe burn injury patients. PMID- 26358389 TI - October 2015 Snapshot Dx Quiz: Linking Science to Patient Care. PMID- 26358390 TI - Microarray Techniques to Analyze Copy-Number Alterations in Genomic DNA: Array Comparative Genomic Hybridization and Single-Nucleotide Polymorphism Array. PMID- 26358391 TI - The complete chloroplast genome sequence of an important medicinal plant Cynanchum wilfordii (Maxim.) Hemsl. (Apocynaceae). AB - Cynanchum wilfordii (Maxim.) Hemsl. is a traditional medicinal herb belonging to the Asclepiadoideae subfamily, whose dried roots have been used as traditional medicine in Asia. The complete chloroplast genome of C. wilfordii was generated by de novo assembly using the small amount of whole genome sequencing data. The chloroplast genome of C. wilfordii was 161 241 bp long, composed of large single copy region (91 995 bp), small single copy region (19 930 bp) and a pair of inverted repeat regions (24 658 bp). The overall GC contents of the chloroplast genome was 37.8%. A total of 114 genes were annotated, which included 80 protein coding genes, 30 tRNA genes and 4 rRNA genes. Phylogenetic analysis with the reported chloroplast genomes revealed that C. wilfordii is most closely related to Asclepias nivea (Caribbean milkweed) and Asclepias syriaca (common milkweed) within the Asclepiadoideae subfamily. PMID- 26358392 TI - Oligothiophene/graphene supramolecular ensembles managing light induced processes: preparation, characterization, and femtosecond transient absorption studies leading to charge-separation. AB - Advances in organic synthetic chemistry combined with the exceptional electronic properties of carbon allotropes, particularly graphene, is the basis used to design and fabricate novel electron donor-acceptor ensembles with desired properties for technological applications. Thiophene-based materials, which are mainly thiophene-containing polymers, are known for their notable electronic properties. In this frame moving from polymer to oligomer forms, new fundamental information would help for a better understanding of their electrochemical and photophysical properties. Furthermore, a successful combination of their electronic properties with those of graphene is a challenging goal. In this study, two oligothiophene compounds, which consist of three and nine thiophene rings and are abbreviated 3T and 9T, respectively, were synthesized and noncovalently associated with liquid phase exfoliated few-layered graphene sheets (abbreviated eG), thus forming donor-acceptor 3T/eG and 9T/eG nanoensembes. Markedly, intra-ensemble electronic interactions between the two components in the ground and excited states were evaluated with the aid of UV-Vis and photoluminescence spectroscopy. Furthermore, redox assays revealed the one electron oxidation of 3T accompanied by one-electron reduction due to eG in 3T/eG, whereas there were two reversible one-electron oxidations of 9T accompanied by one-electron reduction of eG9T/eG. The electrochemical band gap for the 3T/eG and 9T/eG ensembles were calculated and verified, in which the negative free-energy change for the charge-separated state of 3T/eG and 9T/eGvia the singlet excited state of 3T and 9T, respectively, were thermodynamically favorable. Finally, the results of transient pump-probe spectroscopy studies at the femtosecond time scale were supportive of charge transfer type interactions in the 3T/eG and 9T/eG ensembles. The estimated rates for intra-ensemble charge separation were found to be 9.52 * 10(9) s(-1) and 2.2 * 10(11) s(-1), respectively, for 3T/eG and 9T/eG in THF, which reveal moderate to ultrafast photoinduced events in the oligothiophene/graphene supramolecular ensembles. PMID- 26358394 TI - Macrophages: Controlling innate immune memory. PMID- 26358395 TI - Inflammation: TET2: the terminator. PMID- 26358396 TI - Regulatory T Cells: Distinct role in tissue repair. PMID- 26358393 TI - Emerging cytokine networks in colorectal cancer. AB - Cytokine networks are crucial aspects of tumour immunology, particularly for colorectal cancer (CRC), in which inflammation and antitumour immunity are key determinants of disease progression. In this Review, we highlight new insights into the functions of well-known cytokines in CRC, describe recently discovered roles for a growing number of novel players, and emphasize the complexity and therapeutic implications of the cytokine milieu. We also discuss how cancer mutations and epigenetic adaptations influence the oncogenic potential of cytokines, a relatively unexplored area that could yield crucial insights into tumour immunology and facilitate the effective application of cytokine-modulatory therapies for CRC. PMID- 26358397 TI - Factors Influencing Selection of Active Surveillance for Localized Prostate Cancer. AB - OBJECTIVE: To determine how well demographic and clinical factors predict the initiation of Active Surveillance (AS). METHODS: AS has been suggested as a way to reduce overtreatment of men who have prostate cancer; however, factors associated with the decision to choose AS are poorly quantified. Using the Michigan Urological Surgery Improvement Collaborative registry, we identified 2977 men with prostate cancer who made treatment decisions from January 1, 2012, through December 31, 2013. We used chi-square and Wilcoxon tests to examine the association between factors and initiation of AS. Logistic regression models were fit for D'Amico risk categories. Measures of model discrimination and calibration were estimated, including area under the curve (AUC) and Brier score (BS). RESULTS: Patient age, Gleason score, clinical T-stage, urology practice, and tumor volume (greatest percent of a core involved with cancer and proportion of positive cores) were associated with the decision to choose AS in the intermediate-risk cohort (AUC = 0.875, BS = 0.07) and the complete cohort (AUC = 0.89, BS = 0.10). Patient age, urology practice, and tumor volume were significant in the low-risk cohort (AUC = 0.71, BS = 0.22). The addition of urology practice increased AUC in the low-risk cohort from 0.71 to 0.76 and reduced BS from 0.22 to 0.21. CONCLUSION: The urology practice at which a patient is seen is an important predictor for whether patients will initiate AS. Predictions were least accurate for low-risk patients, suggesting that factors such as patient preference play a role in treatment decisions. PMID- 26358398 TI - ODAM inhibits RhoA-dependent invasion in breast cancer. AB - Odontogenic ameloblast-associated protein (ODAM) contributes to cell adhesion. In human cancer, ODAM is down-regulated, and the overexpression of ODAM results in a favourable prognosis; however, the molecular mechanisms underlying ODAM-mediated inhibition of cancer invasion and metastasis remain unclear. Here, we identify a critical role for ODAM in inducing cancer cell adhesion. ODAM induced RhoA activity and the expression of downstream factors, including Rho-associated kinase (ROCK). ODAM-mediated RhoA signalling resulted in actin filament rearrangement by activating PTEN and inhibiting the phosphorylation of AKT. When ODAM is overexpressed in MCF7 breast cancer cells and AGS gastric cancer cells that activate RhoA at high levels, it decreases motility, increases adhesion and inhibits the metastasis of MCF7 cells. Conversely, depletion of ODAM in cancer cells inhibits Rho GTPase activation, resulting in increased cancer migration and invasion. These results suggest that ODAM expression in cells maintains their adhesion, resulting in the prevention of their metastasis via the regulation of RhoA signalling in breast cancer cells. SIGNIFICANCE Breast cancer represents the first most frequent cancer, and the ratio of mortality is high in women. Of utmost importance for reducing risk by breast cancer are their anti-invasion mechanisms, particularly in the non-invasive cancer cells because metastasis is the principal cause of death among cancer patients. ODAM induced RhoA activity. ODAM-mediated RhoA signalling resulted in actin filament rearrangement, increased cell adhesion and inhibited the migration/invasion of MCF7 cells. These results suggest that ODAM expression maintains their adhesion, resulting in the prevention of their metastasis via the regulation of RhoA signalling in breast cancer cells. PMID- 26358399 TI - Differences in larval nutritional requirements and female oviposition preference reflect the order of fruit colonization of Zaprionus indianus and Drosophila simulans. AB - Species coexist using the same nutritional resource by partitioning it either in space or time, but few studies explore how species-specific nutritional requirements allow partitioning. Zaprionus indianus and Drosophila simulans co exist in figs by invading the fruit at different stages; Z. indianus colonizes ripe figs, whereas D. simulans oviposits in decaying fruit. Larvae feed on yeast growing on the fruit, which serves as their primary protein source. Because yeast populations increase as fruit decays, we find that ripe fruit has lower protein content than rotting fruit. Therefore, we hypothesized that Z. indianus and D. simulans larvae differ in their dietary requirements for protein. We used nutritional geometry to assess the effects of protein and carbohydrate concentration in the larval diet on life history characters in both species. Survival, development time, and ovariole number respond differently to the composition of the larval diet, with Z. indianus generally performing better across a wider range of protein concentrations. Correspondingly, we found that Z. indianus females preferred to lay eggs on low protein foods, while D. simulans females chose higher protein foods for oviposition when competing with Z. indianus. We propose the different nutritional requirements and oviposition preference of these two species allows them to temporally partition their habitat. PMID- 26358400 TI - The genetic basis for mating-induced sex differences in starvation resistance in Drosophila melanogaster. AB - Multiple genetic and environmental factors interact to influence starvation resistance, which is an important determinant of fitness in many organisms, including Drosophila melanogaster. Recent studies have revealed that mating can alter starvation resistance in female D. melanogaster, but little is known about the behavioral and physiological mechanisms underlying such mating-mediated changes in starvation resistance. In the present study, we first investigated whether the effect of mating on starvation resistance is sex-specific in D. melanogaster. As indicated by a significant sex*mating status interaction, mating increased starvation resistance in females but not in males. In female D. melanogaster, post-mating increase in starvation resistance was mainly attributed to increases in food intake and in the level of lipid storage relative to lean body weight. We then performed quantitative genetic analysis to estimate the proportion of the total phenotypic variance attributable to genetic differences (i.e., heritability) for starvation resistance in mated male and female D. melanogaster. The narrow-sense heritability (h(2)) of starvation resistance was 0.235 and 0.155 for males and females, respectively. Mated females were more resistant to starvation than males in all genotypes, but the degree of such sexual dimorphism varied substantially among genotypes, as indicated by a significant sex*genotype interaction for starvation resistance. Cross-sex genetic correlation was greater than 0 but less than l for starvation resistance, implying that the genetic architecture of this trait was partially shared between the two sexes. For both sexes, starvation resistance was positively correlated with longevity and lipid storage at genetic level. The present study suggests that sex differences in starvation resistance depend on mating status and have a genetic basis in D. melanogaster. PMID- 26358401 TI - Emotional responses to the experience of cancer 'alarm' symptoms. AB - OBJECTIVE: To qualitatively explore associations between emotional responses to experience of cancer 'alarm' symptoms and help-seeking in a community sample of adults. METHOD: Interviewees (n = 62) were recruited from a community sample (n = 2042) of adults aged >=50 years, who had completed a health survey that included a list of cancer alarm symptoms. Participants who had reported an alarm symptom both at baseline and 3-month follow-up (n = 271), and who had consented to contact (n = 215), constituted the pool for invitations to interview. RESULTS: Over a third of participants (37%) described an emotional response to their symptom experience. In all these cases, there was evidence of awareness of the risk of cancer. Emotional responses were usually either classified as mild ('worry') or severe ('fear'). Worry was often described in the context of a desire to seek medical help, either to rule out cancer or to minimise patient delay. In contrast, the 'fear' group described associations with death, the perceived incurability of cancer, and the consequence of a cancer diagnosis. Where the emotional reaction was fear, medical contact was seen as something to be avoided either because it had no value or because it was preferable not to be told a diagnosis. CONCLUSION: In this community sample, worry about the possibility of cancer was associated with help-seeking, either for reassurance or as part of a 'sensible' strategy to deal with the risk. In contrast, fear was associated with avoiding help-seeking or even thinking about cancer, which could lead to prolonged help-seeking intervals. PMID- 26358402 TI - Amelioration of the Fitness Costs of Antibiotic Resistance Due To Reduced Outer Membrane Permeability by Upregulation of Alternative Porins. AB - The fitness cost of antibiotic resistance is a key parameter in determining the evolutionary success of resistant bacteria. Studies of the effect of antibiotic resistance on bacterial fitness are heavily biased toward target alterations. Here we investigated how the costs in the form of a severely impaired growth rate associated with resistance due to absence of two major outer membrane porins can be genetically compensated. We performed an evolution experiment with 16 lineages of a double mutant of Escherichia coli with the ompCF genes deleted, and reduced fitness and increased resistance to different classes of antibiotics, including the carbapenems ertapenem and meropenem. After serial passage for only 250 generations, the relative growth rate increased from 0.85 to 0.99 (susceptible wild type set to 1.0). Compensation of the costs followed two different adaptive pathways where upregulation of expression of alternative porins bypassed the need for functional OmpCF porins. The first compensatory mechanism involved mutations in the phoR and pstS genes, causing constitutive high-level expression of the PhoE porin. The second mechanism involved mutations in the hfq and chiX genes that disrupted Hfq-dependent small RNA regulation, causing overexpression of the ChiP porin. Although susceptibility was restored in compensated mutants with PhoE overexpression, evolved mutants with high ChiP expression maintained the resistance phenotype. Our findings may explain why porin composition is often altered in resistant clinical isolates and provide new insights into how bypass mechanisms may allow genetic adaptation to a common multidrug resistance mechanism. PMID- 26358403 TI - A single-point mutation enhances dual functionality of a scorpion toxin. AB - Scorpion venom represents a tremendous, hitherto partially explored peptide library that has been proven to be useful not only for understanding ion channels but also for drug design. MeuTXKalpha3 is a functionally unknown scorpion toxin like peptide. Here we describe new transcripts of this gene arising from alternative polyadenylation and its biological function as well as a mutant with a single-point substitution at site 30. Native-like MeuTXKalpha3 and its mutant were produced in Escherichia coli and their toxic function against Drosophila Shaker K(+) channel and its mammalian counterparts (rKv1.1-rKv1.3) were assayed by two-electrode voltage clamp technique. The results show that MeuTXKalpha3 is a weak toxin with a wide-spectrum of activity on both Drosophila and mammalian K(+) channels. The substitution of a proline at site 30 by an asparagine, an evolutionarily conserved functional residue in the scorpion alpha-KTx family, led to an increased activity on rKv1.2 and rKv1.3 but a decreased activity on the Shaker channel without changing the potency on rKv1.1, suggesting a key role of this site in species selectivity of scorpion toxins. MeuTXKalpha3 was also active on a variety of bacteria with lethal concentrations ranging from 4.66 to 52.01MUM and the mutant even had stronger activity on some of these bacterial species. To the best of our knowledge, this is the first report on a bi-functional short chain peptide in the lesser Asian scorpion venom. Further extensive mutations of MeuTXKalpha3 at site 30 could help improve its K(+) channel-blocking and antibacterial functions. PMID- 26358404 TI - Deleterious Germline BLM Mutations and the Risk for Early-onset Colorectal Cancer. AB - Bloom syndrome is an autosomal recessive disorder characterized by chromosomal instability and increased cancer risk, caused by biallelic mutations in the RECQL helicase gene BLM. Previous studies have led to conflicting conclusions as to whether carriers of heterozygous BLM mutations have an increased risk to develop colorectal cancer (CRC). We recently identified two carriers of a pathogenic BLM mutation in a cohort of 55 early-onset CRC patients (<=45 years of age), suggesting an overrepresentation compared to the normal population. Here, we performed targeted sequencing using molecular inversion probes to screen an additional cohort of 185 CRC patients (<=50 years of age) and 532 population matched controls for deleterious BLM mutations. In total, we identified three additional CRC patients (1.6%) and one control individual (0.2%) that carried a known pathogenic BLM mutation, suggesting that these mutations are enriched in early-onset CRC patients (P = 0.05516). A comparison with local and publically available databases from individuals without suspicion for hereditary cancer confirmed this enrichment (P = 0.003534). Analysis of family members of the five BLM mutation carriers with CRC suggests an incomplete penetrance for CRC development. Therefore, these data indicate that carriers of deleterious BLM mutations are at increased risk to develop CRC, albeit with a moderate-to-low penetrance. PMID- 26358405 TI - Efficient refolding of the bifunctional therapeutic fusion protein VAS-TRAIL by a triple agent solution. AB - VAS-TRAIL is a bifunctional fusion protein that combines anti-angiogenic activity with tumor-selective apoptotic activity for enhanced anti-tumor efficacy. VAS TRAIL is expressed as inclusion body in Escherichia coli, but protein refolding is difficult to achieve and results in low yields of bioactive protein. In this study, we describe an efficient method for VAS-TRAIL refolding. The solubilization of aggregated VAS-TRAIL was achieved by a triple agent solution, which consists of an alkaline solution (pH 11.5) containing 0.4M l-arginine and 2M urea. The solubilized protein showed high purity and preserved secondary structure according to fluorescence properties. VAS-TRAIL refolding was performed through stepwise dialysis and resulted in more than 50% recovery of the soluble protein. The function of l-arginine was additive with alkaline pH, as shown by the significant improvement in refolding yield (~30%) by l-arginine-containing solubilization solutions compared with alkaline solubilization solutions without l-arginine. The refolded VAS-TRAIL also showed beta-sheet structures and the propensity for oligomerization. Bioassays showed that the refolded fusion protein exhibited the expected activities, including its apoptotic activities toward tumor and endothelial cells, which proposed its promising therapeutic potential. PMID- 26358406 TI - Immunity, tolerance and autoimmunity in the liver: A comprehensive review. AB - The hepatic immune system is constantly exposed to a massive load of harmless dietary and commensal antigens, to which it must remain tolerant. Immune tolerance in the liver is mediated by a number of specialized antigen-presenting cells, including dendritic cells, Kupffer cells, liver sinusoidal endothelial cells and hepatic stellate cells. These cells are capable of presenting antigens to T cells leading to T cell apoptosis, anergy, or differentiation into regulatory T cells. However, the hepatic immune system must also be able to respond to pathogens and tumours and therefore must be equipped with mechanisms to override immune tolerance. The liver is a site of accumulation of a number of innate lymphocyte populations, including natural killer cells, CD56(+) T cells, natural killer T cells, gammadelta T cells, and mucosal-associated invariant T cells. Innate lymphocytes recognize conserved metabolites derived from microorganisms and host cells and respond by killing target cells or promoting the differentiation and/or activation of other cells of the immune system. Innate lymphocytes can promote the maturation of antigen-presenting cells from their precursors and thereby contribute to the generation of immunogenic T cell responses. These cells may be responsible for overriding hepatic immune tolerance to autoantigens, resulting in the induction and maintenance of autoreactive T cells that mediate liver injury causing autoimmune liver disease. Some innate lymphocyte populations can also directly mediate liver injury by killing hepatocytes or bile duct cells in murine models of hepatitis, whilst other populations may protect against liver disease. It is likely that innate lymphocyte populations can promote or protect against autoimmune liver disease in humans and that these cells can be targeted therapeutically. Here I review the cellular mechanisms by which hepatic antigen-presenting cells and innate lymphocytes control the balance between immunity, tolerance and autoimmunity in the liver. PMID- 26358407 TI - Pathways linking drug use and labour market trajectories: the role of catastrophic events. AB - People affected by substance use disorders often experience sub-optimal employment outcomes. The role of drug use in processes that produce and entrench labour market precarity among people who inject drugs (PWID) have not, however, been fully described. We recruited 22 PWID from ongoing prospective cohort studies in Vancouver, Canada, with whom we conducted semi-structured retrospective interviews and then employed a thematic analysis that drew on concepts from life course theory to explore the mechanisms and pathways linking drug use and labour market trajectories. The participants' narratives identified processes corresponding to causation, whereby suboptimal employment outcomes led to harmful drug use; direct selection, where impairment, health complications or drug-seeking activities selected individuals out of employment; and indirect selection, where external factors, such as catastrophic events, marked the initiation or intensification of substance use concurrent with sudden changes in capacities for employment. Catastrophic events linking negative transitions in both drug use and labour market trajectories were of primary importance, demarcating critical initiation and transitional events in individual risk trajectories. These results challenge conventional assumptions about the primacy of drug use in determining employment outcomes among PWID and suggest the importance of multidimensional support to mitigate the initiation, accumulation and entrenchment of labour market and drug-related disadvantage. PMID- 26358408 TI - Micronucleus scoring: a potential adjunct for diagnosis of endometrial adenocarcinoma on cervical samples. AB - Micronucleus (MN) is an additional, small nucleus formed due to failure of incorporation of a fragment or the whole chromosome into the main daughter nuclei during cell division. MN scoring is a useful indicator of exposure to genotoxic agents and of malignancy. This study was conducted to know whether the MN score was significantly different in cervical cytology smears of patients with endometrial carcinoma, atypical and benign cells. Three groups of cervical smears were taken up for MN scoring: Group 'A' included benign endometrial cells, Group 'B', atypical glandular cells - endometrial and Group 'C', endometrial adenocarcinoma. Post hoc analysis of variance test was used to determine significant differences between the three groups. There were 30 cases in Group 'A', 31 cases in Group 'B' and 39 cases in Group 'C'. The mean MN score was 0.67 +/- 0.711 in Group A, 1.74 +/- 0.930 in Group B and 4.10 +/- 2.500 in Group C. MN scores were significantly different between all three groups (p < 0.05). The MN score is significantly higher in cervical smears of patients with endometrial carcinoma; as compared to smears showing atypical and benign cells and that this finding may be useful for further research. PMID- 26358409 TI - Migration of encephalitogenic CD8 T cells into the central nervous system is dependent on the alpha4beta1-integrin. AB - Although CD8 T cells are key players in neuroinflammation, little is known about their trafficking cues into the central nervous system (CNS). We used a murine model of CNS autoimmunity to define the molecules involved in cytotoxic CD8 T cell migration into the CNS. Using a panel of mAbs, we here show that the alpha4beta1-integrin is essential for CD8 T-cell interaction with CNS endothelium. We also investigated which alpha4beta1-integrin ligands expressed by endothelial cells are implicated. The blockade of VCAM-1 did not protect against autoimmune encephalomyelitis, and only partly decreased the CD8(+) T-cell infiltration into the CNS. In addition, inhibition of junctional adhesion molecule-B expressed by CNS endothelial cells also decreases CD8 T-cell infiltration. CD8 T cells may use additional and possibly unidentified adhesion molecules to gain access to the CNS. PMID- 26358410 TI - An integrated model of social environment and social context for pediatric rehabilitation. AB - This article considers the conceptualization and operationalization of "social environment" and "social context" with implications for research and practice with children and youth with impairments. We first discuss social environment and social context as constructs important for understanding interaction between external environmental qualities and the individual's experience. The article considers existing conceptualizations within psychological and sociological bodies of literature, research using these concepts, current developmental theories and issues in the understanding of environment and participation within rehabilitation science. We then describe a model that integrates a person-focused perspective with an environment-focused perspective and that outlines the mechanisms through which children/youth and social environment interact and transact. Finally, we consider the implications of the proposed model for research and clinical practice. This conceptual model directs researchers and practitioners toward interventions that will address the mechanisms of child environment interaction and that will build capacity within both children and their social environments, including families, peers groups and communities. Health is created and lived by people within the settings of their everyday life; where they learn, work, play, and love [p.2]. IMPLICATIONS FOR REHABILITATION: Understanding how social environment and personal factors interact over time to affect the development of children/youth can influence the design of services for children and youth with impairments. The model described integrates the individual-focused and environment-focused perspectives and outlines the mechanisms of the ongoing reciprocal interaction between children/youth and their social environments: provision of opportunities, resources and supports and contextual processes of choice, active engagement and collaboration. Addressing these mechanisms could contribute to creating healthier environments in which all children, including children with impairments, have experiences that lead to positive developmental benefits. PMID- 26358411 TI - Reproducibility of Buccal Gingival Profile Using a Custom Pick-Up Impression Technique: A 2-Year Prospective Multicenter Study. AB - PURPOSE: The aim of this study was to transfer the provisional restoration emergence profile to the final implant-supported restoration and to buccal gingival margin (BGM) stability after 2 years of function. MATERIALS AND METHODS: A total of 33 patients were recruited for treatment of single gaps by means of 33 implant-supported restorations. Fixed provisional crowns were screwed to the fixture and adjusted until the complete peri-implant soft tissue maturation was achieved. After 12 weeks, a second fixture impression was taken by means of a pick-up customization technique in order to transfer the clinical aspect of the peri-implant soft tissues to the master cast. A definitive restoration was delivered. A standardized method from digital photographs was used to assess the gingival margin modification (BGM) from the provisional (P) to the definitive prosthesis installation at baseline (D0), and after 1 (D1) and 2 years (D2) of function. Also, marginal bone loss (MBL) was calculated after 1 (D1) and 2 years (D2) of definitive restoration function. RESULTS: The BGM index at the time of the final restoration installation (D0) was 0.12 +/- 0.33 mm if compared with the BGM position of the provisional restoration (P); it was of 0.12 +/- 0.46 mm after 1-year of follow-up (D1) and of 0.31 +/- 0.21 after 2 years of function (D2). No significant difference was calculated between measurements in different follow-up visits (p > 0.05). No significant MBL was measured between the baseline (D0) and the 1-year follow-up (p = 0.816) with a mean MBL value of 0.2 +/- 0.1 mm. Similar result was calculated after 2 years (p = 0.684) with a mean MBL value of 0.3 +/- 0.2. CONCLUSION: A modified impression pick-up may be helpful to reproduce the gingival margin position from the provisional to the definitive restoration. Moreover, the gingival zenith position during the follow-up period seemed to be stable. CLINICAL SIGNIFICANCE: The modification of the standard impression pick up technique may contribute to reproducing a natural emergence profile of esthetic implant prosthetic restorations (from the provisional to the definitive restoration.) With this technique, implant soft tissues stability around CAD-CAM (computer aided design-computer aided manufacturing) abutments can be easily obtained, and the customized abutment shape may better support the scalloped peri implant soft tissues architecture, especially in anterior areas. PMID- 26358412 TI - Clinical and immunological findings in 104 cases of paraneoplastic pemphigus. AB - BACKGROUND: Although there are many reports of sporadic patients with paraneoplastic pemphigus (PNP), only a few systematic studies on large cohorts of patients with PNP have been reported. OBJECTIVES: To analyse the clinical and immunological findings in a large cohort of patients with PNP. METHODS: This retrospective study consisted of 104 patients with PNP. Clinical and histopathological manifestations, associated neoplasms, complicating diseases, prognosis and results of immunofluorescence, immunoblotting and enzyme-linked immunosorbent assays (ELISAs) were analysed. RESULTS: The clinical and histopathological findings in this study were generally similar to those in previous reports. The most common associated neoplasms included malignant lymphomas, malignant solid tumours and Castleman disease, in that order, while 12 patients had no detectable tumours. Novel ELISAs for desmocollins (Dscs) showed that 19 (18.6%), 42 (41.2%) and 62 (60.8%) of 102 patients with PNP showed antibodies to Dsc1, Dsc2 and Dsc3, respectively. Thirty-two (60%) of 53 patients had antibodies to alpha-2-macroglobulin-like protein 1 (A2ML1). We found statistically significant correlations between positive desmoglein 3 reactivity and genital lesions, and between positive desmoglein 3 reactivity and bronchiolitis obliterans. CONCLUSIONS: We consider that antibodies to Dscs and A2ML1 are useful for the diagnosis of PNP. PMID- 26358413 TI - Cardiac auscultation via simulation: a survey of the approach of UK medical schools. AB - BACKGROUND: A decline in clinical skills of medical students and junior doctors is well documented. We aim to determine how the 32 UK medical schools utilise simulated heart sounds to develop medical students' cardiac auscultation skills. METHODS: Representatives of all 32 UK medical schools were contacted with a survey questionnaire. Data analysis was carried out using SPSS. Continuous variables e.g. teaching group size were described using median and interquartile range (IQR). RESULTS: 27 Medical schools use a form of simulated heart sounds as a teaching method (2 representatives were unsure, 3 did not respond). This teaching is mandatory in 17 schools. Simulation-based teaching tends to be offered during 3rd year of medical training [median = 3rd year, interquartile range (IQR) 2-3]. Seven medical schools offered simulation teaching more than once. The median number of students in each session was 7.5 [IQR = 5.5-9.5]. One medical school reported that they were unsure how best to implement the heart sound simulation into the medical undergraduate curriculum. CONCLUSION: The results of our survey of all the UK medical schools suggest that heart sound simulation are used mainly as an introduction to heart murmurs rather than a tool for repetitive practice, complementing clinical experience. Most medical schools do not measure the impact of such teaching on clinical examination. PMID- 26358414 TI - Does the Value Circle Exist Within Persons or Only Across Persons? AB - This study tests whether the Schwartz (1992) value circle exists within individuals, not only across individuals, thereby providing evidence for the within-person rationale underlying the value circle. We analyze responses from five samples (a representative sample in Britain, a general population sample in the United States, and university students in Britain and Iran) varying in value measures of the Schwartz value theory (SVS, PVQ40, PVQ21). An unfolding model is used to map each person's value profile into a two-dimensional space representing both persons and values. In all samples, clear value circles were found, with values ordered around the circle largely according to the theory. The model also represents most individuals well. The value circle exists within individuals, providing strong support for the underlying within-person rationale for the Schwartz (1992) value theory. The unfolding analysis allows identifying which persons fit the model less well and in which way, identifying how meaningful subgroups differ in their value profiles, and testing whether meaningful subgroups have different value structures. The model opens up many new possibilities for research linking values to other variables. PMID- 26358415 TI - Molecular Genetic Analysis of Glucan Branching Enzymes from Plants and Bacteria in Arabidopsis Reveals Marked Differences in Their Functions and Capacity to Mediate Starch Granule Formation. AB - The major component of starch is the branched glucan amylopectin, the branching pattern of which is one of the key factors determining its ability to form semicrystalline starch granules. Here, we investigated the functions of different branching enzyme (BE) types by expressing proteins from maize (Zea mays BE2a), potato (Solanum tuberosum BE1), and Escherichia coli (glycogen BE [EcGLGB]) in Arabidopsis (Arabidopsis thaliana) mutant plants that are deficient in their endogenous BEs and therefore, cannot make starch. The expression of each of these three BE types restored starch biosynthesis to differing degrees. Full complementation was achieved using the class II BE ZmBE2a, which is most similar to the two endogenous Arabidopsis isoforms. Expression of the class I BE from potato, StBE1, resulted in partial complementation and high amylose starch. Expression of the glycogen BE EcGLGB restored only minimal amounts of starch production, which had unusual chain length distribution, branch point distribution, and granule morphology. Nevertheless, each type of BE together with the starch synthases and debranching enyzmes were able to create crystallization competent amylopectin polymers. These data add to the knowledge of how the properties of the BE influence the final composition of starch and fine structure of amylopectin. PMID- 26358416 TI - Class XI Myosins Move Specific Organelles in Pollen Tubes and Are Required for Normal Fertility and Pollen Tube Growth in Arabidopsis. AB - Pollen tube growth is an essential aspect of plant reproduction because it is the mechanism through which nonmotile sperm cells are delivered to ovules, thus allowing fertilization to occur. A pollen tube is a single cell that only grows at the tip, and this tip growth has been shown to depend on actin filaments. It is generally assumed that myosin-driven movements along these actin filaments are required to sustain the high growth rates of pollen tubes. We tested this conjecture by examining seed set, pollen fitness, and pollen tube growth for knockout mutants of five of the six myosin XI genes expressed in pollen of Arabidopsis (Arabidopsis thaliana). Single mutants had little or no reduction in overall fertility, whereas double mutants of highly similar pollen myosins had greater defects in pollen tube growth. In particular, myo11c1 myo11c2 pollen tubes grew more slowly than wild-type pollen tubes, which resulted in reduced fitness compared with the wild type and a drastic reduction in seed set. Golgi stack and peroxisome movements were also significantly reduced, and actin filaments were less organized in myo11c1 myo11c2 pollen tubes. Interestingly, the movement of yellow fluorescent protein-RabA4d-labeled vesicles and their accumulation at pollen tube tips were not affected in the myo11c1 myo11c2 double mutant, demonstrating functional specialization among myosin isoforms. We conclude that class XI myosins are required for organelle motility, actin organization, and optimal growth of pollen tubes. PMID- 26358417 TI - Exocyst-Positive Organelles and Autophagosomes Are Distinct Organelles in Plants. AB - Autophagosomes are organelles that deliver cytosolic proteins for degradation in the vacuole of the cell. In contrast, exocyst-positive organelles (EXPO) deliver cytosolic proteins to the cell surface and therefore represent a form of unconventional protein secretion. Because both structures have two boundary membranes, it has been suggested that they may have been falsely treated as separate entities. Using suspension culture cells and root tissue cells of transgenic Arabidopsis (Arabidopsis thaliana) plants expressing either the EXPO marker Arabidopsis Exo70E2-GFP or the autophagosome marker yellow fluorescent protein (YFP)-autophagy-related gene 8e/f (ATG8e/f), and using specific antibodies against Exo70E2 and ATG8, we have now established that, in normally growing cells, EXPO and autophagosomes are distinct from one another. However, when cells/roots are subjected to autophagy induction, EXPO as well as autophagosomes fuse with the vacuole. In the presence of concanamycin A, the punctate fluorescent signals from both organelles inside the vacuole remain visible for hours and overlap to a significant degree. Tonoplast staining with FM4-64/YFP-Rab7-like GTPase/YFP-vesicle-associated membrane protein711 confirmed the internalization of tonoplast membrane concomitant with the sequestration of EXPO and autophagosomes. This suggests that EXPO and autophagosomes may be related to one another; however, whereas induction of autophagy led to an increase in the amount of ATG8 recruited to membranes, Exo70E2 did not respond in a similar manner. PMID- 26358419 TI - Confirmation of autosomal recessive inheritance of COL2A1 mutations in spondyloepiphyseal dysplasia congenita: Lessons for genetic counseling. PMID- 26358420 TI - Targeting oncogenic BRAF and aberrant MAPK activation in the treatment of cutaneous melanoma. AB - BRAF and MEK inhibitors, alone or in combination, are highly active in the 40% of patients with BRAF mutant metastatic melanoma. Despite this activity resistance often develops in patients treated with these agents. This review summarises the biology of the mitogen activated protein kinase (MAPK) pathway, with particular reference to the effects of BRAF and MEK inhibitors in BRAF mutant melanoma. The clinical and molecular predictors of response and mechanisms of resistance are discussed in detail along with the biological rationale and evidence for future treatment strategies in both MAPK inhibitor naive and resistant BRAF mutant melanoma. PMID- 26358418 TI - A Kelch Domain-Containing F-Box Coding Gene Negatively Regulates Flavonoid Accumulation in Muskmelon. AB - The flavonoids are phenylpropanoid-derived metabolites that are ubiquitous in plants, playing many roles in growth and development. Recently, we observed that fruit rinds of yellow casaba muskmelons (Cucumis melo 'Inodorous Group') accumulate naringenin chalcone, a yellow flavonoid pigment. With RNA-sequencing analysis of bulked segregants representing the tails of a population segregating for naringenin chalcone accumulation followed by fine mapping and genetic transformation, we identified a Kelch domain-containing F-box protein coding (CmKFB) gene that, when expressed, negatively regulates naringenin chalcone accumulation. Additional metabolite analysis indicated that downstream flavonoids are accumulated together with naringenin chalcone, whereas CmKFB expression diverts the biochemical flux toward coumarins and general phenylpropanoids. These results show that CmKFB functions as a posttranscriptional regulator that diverts flavonoid metabolic flux. PMID- 26358421 TI - Critical review about MDM2 in cancer: Possible role in malignant mesothelioma and implications for treatment. AB - The tumor suppressor p53 regulates genes involved in DNA repair, metabolism, cell cycle arrest, apoptosis and senescence. p53 is mutated in about 50% of the human cancers, while in tumors with wild-type p53 gene, the protein function may be lost because of overexpression of Murine Double Minute 2 (MDM2). MDM2 targets p53 for ubiquitylation and proteasomal degradation. p53 reactivation through MDM2 inhibitors seems to be a promising strategy to sensitize p53 wild-type cancer cells to apoptosis. Moreover, additional p53-independent molecular functions of MDM2, such as neoangiogenesis promotion, have been suggested. Thus, MDM2 might be a target for anticancer treatment because of its antiapoptotic and proangiogenetic role. Malignant pleural mesothelioma (MPM) is an aggressive asbestos-related tumor where wild-type p53 might be present. The present review gives a complete landscape about the role of MDM2 in cancer pathogenesis, prognosis and treatment, with particular focus on Malignant Pleural Mesothelioma. PMID- 26358422 TI - Special issues in fertility preservation for gynecologic malignancies. AB - Gynecologic malignancies account for 1,09 million new cancer cases worldwide consisting of about 12% of tumors affecting female population. About 10% of all female cancer survivors are younger than 40 years of age. Since cancers affecting female genital organs are usually treated by radical surgery, chemotherapy or chemoradiation approaches that induce permanent damage of reproductive functions, the development of strategies for fertility preservation represent one of the most important goals for gynecologic oncology. In this scenario, the newly defined oncofertility discipline acquires increasing interest, offering patients maximal chances to make an adequate decision about future fertility, based on their oncologic diagnosis and prognosis. However, the majority of physicians do not pay particular attention to these issues, even if impressive progresses have been made in this field in the last decades. Possibly, it is due to the lack of strong evidences from clinical trials without an adequate number of cases to establish safety and efficacy of these procedures. In this review we will discuss the most recently debated options for fertility preservation in gynecologic oncology, highlighting issues and controversies related to oncofertility. PMID- 26358424 TI - Bioethics. Introduction. PMID- 26358425 TI - A Parent's Journey: Incorporating Principles of Palliative Care into Practice for Children with Chronic Neurologic Diseases. AB - Rather than in conflict or in competition with the curative model of care, pediatric palliative care is a complementary and transdisciplinary approach used to optimize medical care for children with complex medical conditions. It provides care to the whole child, including physical, mental, and spiritual dimensions, in addition to support for the family. Through the voice of a parent, the following case-based discussion demonstrates how the fundamentals of palliative care medicine, when instituted early in the course of disease, can assist parents and families with shared medical decision making, ultimately improving the quality of life for children with life-limiting illnesses. Pediatric neurologists, as subspecialists who provide medical care for children with chronic and complex conditions, should consider invoking the principles of palliative care early in the course of a disease process, either through applying general facets or, if available, through consultation with a specialty palliative care service. PMID- 26358426 TI - Identifying the Unique Aspects of Adolescent and Young Adult Palliative Care: A Case Study to Propel Programmatic Changes in Pediatric Hospitals. AB - Using a case study, in this article we seek to highlight how the distinct developmental needs of adolescent and young adult patients facing a life threatening condition require a different approach to patient care by pediatric health care workers. The case underscores pitfalls in using a pediatric construct of care in areas of pain management, social stressors, and advanced care planning, and suggests programs to implement for improvement, including partnership with psychiatry, substance abuse, and palliative care specialists. PMID- 26358423 TI - Concentration of isoprene in artificial and thylakoid membranes. AB - Isoprene emission protects plants from a variety of abiotic stresses. It has been hypothesized to do so by partitioning into cellular membranes, particularly the thylakoid membrane. At sufficiently high concentrations, this partitioning may alter the physical properties of membranes. As much as several per cent of carbon taken up in photosynthesis is re-emitted as isoprene but the concentration of isoprene in the thylakoid membrane of rapidly emitting plants has seldom been considered. In this study, the intramembrane concentration of isoprene in phosphatidylcholine liposomes equilibrated to a physiologically relevant gas phase concentration of 20 MUL L(-1) isoprene was less than predicted by ab initio calculations based on the octanol-water partitioning coefficient of isoprene while the concentration in thylakoid membranes was more. However, the concentration in both systems was roughly two orders of magnitude lower than previously assumed. High concentrations of isoprene (2000 MUL L(-1) gas phase) failed to alter the viscosity of phosphatidylcholine liposomes as measured with perylene, a molecular probe of membrane structure. These results strongly suggest that the physiological concentration of isoprene within the leaves of highly emitting plants is too low to affect the dynamics of thylakoid membrane acyl lipids. It is speculated that isoprene may bind to and modulate the dynamics of thylakoid embedded proteins. PMID- 26358427 TI - Cognitive Enhancement: Treating or Cheating? AB - In this article I provide an overview of the moral and medical questions surrounding the use of cognitive enhancers. This discussion will be framed in light of 4 key considerations: (1) is there a difference between therapy and enhancement? (2) How safe are these interventions? (3) Is the use of nootropics cheating? (4) Would enhancers create a further divide of social inequality where only the very wealthy have access to them? PMID- 26358428 TI - Ethical Challenges in Early-Phase Pediatric Research for Life-Limiting Illness. AB - Research with children is necessary to assure more effective treatments and potential cures of childhood illnesses. Ethical conduct of research requires minimizing the inherent risks of research, especially when it involves vulnerable populations such as children. Duchenne muscular dystrophy (DMD) is a progressive and fatal disease with no Food and Drug Administration-approved treatment. Clinical trials investigating so-called gene therapies are viewed by many in the DMD community with great promise. The goal of research is to secure generalizable knowledge and not directly benefit patients, yet many parents of boys with DMD hope, and even expect, that their sons will derive medical benefit by participating in early-phase "gene therapy" trials, raising concern for the therapeutic misconception. Physician-investigators must assist patient-subjects to distinguish realistic from unrealistic hope while maintaining reasonable expectations. In this article, I examine the therapeutic misconception and related concepts as framed within the context of "gene therapy" for DMD. PMID- 26358429 TI - Ethical Issues in Neuroprognostication after Severe Pediatric Brain Injury. AB - Neurologic outcome prediction, or neuroprognostication, after severe brain injury in children is a challenging task and has many ethical dimensions. Neurologists and intensivists are frequently asked by families to predict functional recovery after brain injury to help guide medical decision making despite limited outcome data. Using two clinical cases of children with severe brain injury from different mechanisms: hypoxic-ischemic injury secondary to cardiac arrest and traumatic brain injury, this article first addresses the importance of making a correct diagnosis in a child with a disorder of consciousness and then discusses some of the clinical challenges with deducing an accurate and timely outcome prediction. We further explore the ethical obligations of physicians when supporting parental decision making. We highlight the need to focus on how to elicit family values for a brain injured child, how to manage prognostic uncertainty, and how to effectively communicate with families in these challenging situations. We offer guidance for physicians when they have diverging views from families on aggressiveness of care or feel pressured to prognosticate with in a "window of opportunity" for limiting or withdrawing life sustaining therapies. We conclude with a discussion of the potential influence of emerging technologies, specifically advanced functional neuroimaging, on neurologic outcome prediction after severe brain injury. PMID- 26358430 TI - The Philosophical Basis of Bioethics. AB - In this article, I consider in what sense bioethics is philosophical. Philosophy includes both analysis and synthesis. Analysis focuses on central concepts in a domain, for example, informed consent, death, medical futility, and health. It is argued that analysis should avoid oversimplification. The synthesis or synoptic dimension prompts people to explain how their views have logical assumptions and implications. In addition to the conceptual elements are the evaluative and empirical dimensions. Among its functions, philosophy can be a form of prophylaxis--helping people avoid some commonly accepted questionable theories. Generally, recent philosophy has steered away from algorithms and deductivist approaches to ethical justification. In bioethics, philosophy works in partnership with a range of other disciplines, including pediatrics and neurology. PMID- 26358431 TI - Health Care Rationing in a Just Society: The Clinical Effectiveness Model. AB - Representing 18% of gross domestic product, and projected to increase to 20% by 2022, health care costs in the United States are an unsustainable expense. The clinical effectiveness model of cost containment is an ethical and self sustaining paradigm that can assist bending the health care-cost curve. As envisioned by Buyx et al, clinically effective care is aimed at making the practice of medicine more explicitly evidence based with the goals of improving clinical success, efficiency, and value. I provide a vision for applying the clinical effectiveness model to the American health care system. I illustrate its use with 2 examples from the practice of child neurology: DOC-band (helmet therapy) for the treatment of positional plagiocephaly-relatively inexpensive but ineffective, and adrenocorticotropic hormone for the treatment of infantile spasms-expensive but effective. PMID- 26358432 TI - Spectral-domain optical coherence tomography appearance of preretinal granulomas in toxoplasma posterior uveitis with arterial occlusion. PMID- 26358433 TI - [Unilateral congenital cataract with persistence of Cloquet's canal]. PMID- 26358434 TI - [Pseudo-Coats diagnosed in 58-year-old woman]. PMID- 26358435 TI - [Epidemiological, clinical and therapeutic features of pediatric ocular injuries in an eye emergency unit in Ile-de-France]. AB - INTRODUCTION: Ocular and orbital trauma is a leading cause of acquired monocular blindness in childhood. These injuries differ from those in adults in some aspects of the management and prognosis, notably the risk of amblyopia. The goal of this study was to analyze the epidemiological, clinical and therapeutic features of ocular trauma in children who consulted in an eye emergency department in Ile-de-France. PATIENTS AND METHODS: This was a descriptive, prospective and longitudinal study. Over a period of 6 months, we included children aged 15 years old or less, who consulted during calls for ocular trauma. Each child received an ophthalmologic examination as complete as his or her condition and cooperation permitted. Mechanical injuries of the eyeball and chemical ocular burns were distributed respectively according to the Birmingham Eye Trauma Terminology and Dua's classification. The visual prognosis was defined as the best corrected visual acuity of the affected eye, measured at the conclusion of treatment. RESULTS: Among 586 children who consulted during the study period, 265 suffered from ocular trauma (45.22%). The male:female ratio was 1.6:1. The main places of occurrence of the injuries were home (64.15%) and school (18.11%). Injuries from finger nail scratch were the most frequent (12.45%). One hundred and fifty-seven patients consulted within 6 hours (59.19%). The cornea was the predominant site of the injury (44.40%). Mechanical injuries of the eyeball accounted for 75% of cases. The incidence of ocular chemical burns was 6.41%. Eyelid and orbital injuries were observed in 22.26% and 2.26% of cases respectively. Surgical treatment was required in 6.79% of cases. The incidence of hospitalization was 3.02% with a mean length of stay of 3 days. Four children developed sequelae, including 2 corneal scars and 2 cataracts. No case of blindness was recorded. DISCUSSION: The high frequency of traumatic ocular and orbital pathology in our study may be due to its sudden and accidental onset, leading parents to seek emergency care. Most injuries occurred at home and at school, which reflects the presence in these places of potential hazards, often unrealized or neglected. The low frequency of open-globe injury may be related to the ubiquitous recruitment. Indeed, in studies including only severe trauma, this rate may reach 73.4%. This clinical presentation is associated with a poor prognosis because of the risk of infection and sequelae causing decreased visual acuity and amblyopia. Few children were hospitalized. This could be explained by the predominance of mild to moderate trauma. CONCLUSION: Ocular trauma accounts for nearly half of pediatric conditions encountered in the eye emergency unit. Adequate emergency care improves the visual prognosis. PMID- 26358436 TI - Ocular perforation post-blepharoplasty. PMID- 26358437 TI - [The parameter "relative survival": Analysis of regional cancer registry data for prostate cancer]. AB - BACKGROUND: There is a lack of comparability of relative survival rates due to differences in regional mortality. OBJECTIVE: How should relative survival be calculated to be able to compare regional cancer mortality? MATERIALS AND METHODS: Calculation of relative survival rates of prostate cancer patients from a regional cancer registry using diagnosis year and stage, based on differential mortality tables. RESULTS: Calculation of relative survival for all prostate cancer patients shows a very slight excess mortality after 5 years compared to a matched general population. Introduction of new imaging techniques and PSA screening led to a change in the distribution of diagnosed stages. Differentiation by stage is therefore essential. Thus, patients with UICC stage I, II, and III have a very low excess mortality, while patients with a UICC stage IV have a significantly higher excess mortality; however, it is very surprising that the excess mortality of patients without specification of the UICC stage is similarly unfavorable as in the case of patients with UICC stage IV. CONCLUSION: If data from a regional cancer registry are used, adequate mortality tables from the catchment area of the registry should be used as a reference due to regional mortality differences. Thus, progress in patient survival can be more precisely mapped. With respect to prostate cancer patients, differential consideration by stage is also necessary because improved early detection methods has led to a change in the stage distribution and, thus, survival. PMID- 26358438 TI - [Melanosis of the urinary bladder]. AB - Melanosis of the bladder is rare. Only 10 cases have been described in the literature. We present the case of an 80-year-old woman with neurogenic lower urinary tract dysfunction due to spinal paralysis. During the diagnostic work-up which included cystoscopy, black spots in the bladder wall were observed. Histopathological evaluation revealed a benign suburothelial melanosis. Thus, with cystoscopic suspicion of a malignancy (melanoma), a biopsy is mandatory and regular cystoscopic follow-up is recommended. PMID- 26358439 TI - Micromonospora fluostatini sp. nov., isolated from marine sediment. AB - The novel actinomycete strain PWB-003T, which produced fluostatins B and C antibiotics, was isolated from nearshore sediment collected from Panwa Cape, Phuket Province, Thailand. Data from the present polyphasic study indicated that strain PWB-003T represented a member of the genus Micromonospora. It produced single spores on substrate mycelia and contained meso-diaminopimelic acid in the cell-wall peptidoglycan. Whole-cell hydrolysate contained ribose, xylose, arabinose, mannose and glucose. The predominant menaquinone was MK-10 (H4). Cellular fatty acids comprised C18 : 1omega9c, iso-C16 : 0, anteiso-C17 : 0, iso C15 : 0 and iso-C17 : 0. On the basis of 16S rRNA gene sequence similarity analysis, the novel strain was closely related to Micromonospora eburnea LK2-10T (99.38 %), Micromonospora chaiyaphumensis MC5-1T (99.16 %), Micromonospora yangpuensis FXJ6.011T (98.97 %), Micromonospora echinaurantiaca DSM 43904T (98.97 %), Micromonospora pallida DSM 43817T (98.97 %), Micromonospora sagamiensis DSM 43912T and Micromonospora auratinigra JCM 12357T (both 98.97 %). The G+C content of the DNA was 74.5 mol%. DNA-DNA relatedness values among strain PWB-003T and related type strains ranged from 11.3 +/- 1.3 to 38.8 +/- 1.1 %. On the basis of these observations, strain PWB-003T could be distinguished from its closely related type strains and is considered to represent a novel species of the genus Micromonospora, for which the name Micromonospora fluostatini sp. nov. (type strain PWB-003T = JCM 30529T = PCU 341T = TISTR 2345T) is proposed. PMID- 26358440 TI - Government inaction over social injustice is failing children, says Marmot. PMID- 26358441 TI - BCVA welcomes roll out of badger cull to Dorset. PMID- 26358442 TI - New qualification for OVs involved in Cymorth TB in Wales. PMID- 26358443 TI - Undertakings accepted in disciplinary case. PMID- 26358444 TI - Raising awareness of sustainable management of liver fluke in sheep. PMID- 26358445 TI - 2001 FMD outbreak remembered. PMID- 26358446 TI - New chairman for greyhound charity. PMID- 26358447 TI - Guidelines on epilepsy. PMID- 26358448 TI - Spanish honour for UK graduate. PMID- 26358449 TI - Veterinary medicines: product update. PMID- 26358450 TI - Vets and aquaculture: an evolving relationship. PMID- 26358452 TI - Correction. PMID- 26358451 TI - Bovine tuberculosis: how likely is a skin test reactor to be uninfected? PMID- 26358453 TI - Developing primary health care. PMID- 26358454 TI - Hepatic lipodystrophy of Galloway calves. PMID- 26358455 TI - Evidence-based medicine. PMID- 26358456 TI - Professional notabilia. PMID- 26358462 TI - Studying veterinary medicine in Warsaw. PMID- 26358463 TI - Ten-minute chat. PMID- 26358464 TI - Genetic incorporation of recycled unnatural amino acids. AB - The genetic incorporation of unnatural amino acids (UAAs) into proteins has been a useful tool for protein engineering. However, most UAAs are expensive, and the method requires a high concentration of UAAs, which has been a drawback of the technology, especially for large-scale applications. To address this problem, a method to recycle cultured UAAs was developed. The method is based on recycling a culture medium containing the UAA, in which some of essential nutrients were resupplemented after each culture cycle, and induction of protein expression was controlled with glucose. Under optimal conditions, five UAAs were recycled for up to seven rounds of expression without a decrease in expression level, cell density, or incorporation fidelity. This method can generally be applied to other UAAs; therefore, it is useful for reducing the cost of UAAs for genetic incorporation and helpful for expanding the use of the technology to industrial applications. PMID- 26358465 TI - Early motherhood: a qualitative study exploring the experiences of African Australian teenage mothers in greater Melbourne, Australia. AB - BACKGROUND: Motherhood is a significant and important aspect of life for many women around the globe. For women in communities where motherhood is highly desired, motherhood is considered crucial to the woman's identity. Teenage motherhood, occurring at a critical developmental stage of teenagers' lives, has been identified as having adverse social and health consequences. This research aimed to solicit the lived experiences of African Australian young refugee women who have experienced early motherhood in Australia. METHODS: This qualitative research used in-depth interviews. The research methods and analysis were informed by intersectionality theory, phenomenology and a cultural competency framework. Sixteen African born refugee young women who had experienced teenage pregnancy and early motherhood in Greater Melbourne, Australia took part in this research. Interviews were audio recorded, transcribed and data analysed using thematic content analysis. Ethics approval for this research was granted by Victoria University Human Research Ethics committee. RESULTS: Motherhood brings increased responsibilities, social recognition, and a sense of purpose for young mothers. Despite the positive aspects of motherhood, participants faced challenges that affected their lives. Most often, the challenges included coping with increased responsibilities following the birth of the baby, managing the competing demands of schooling, work and taking care of a baby in a site of settlement. The young mothers indicated they received good support from their mothers, siblings and close friends, but rarely from the father of their baby and the wider community. Participants felt that teenage mothers are frowned upon by their wider ethnic communities, which left them with feelings of shame and embarrassment, despite the personal perceived benefits of achieving motherhood. CONCLUSIONS: We propose that service providers and policy makers support the role of the young mothers' own mother, sisters, their grandmothers and aunts following early motherhood. Such support from significant females will help facilitate young mothers' re-engagement with education, work and other aspects of life. For young migrant mothers, this is particularly important in order to facilitate settlement in a new country and reduce the risk of subsequent mistimed pregnancies. Service providers need to expand their knowledge and awareness of the specific needs of refugee teen mothers living in 'new settings'. PMID- 26358466 TI - Examining patient comprehension of emergency department discharge instructions: Who says they understand when they do not? AB - Patient comprehension of emergency department (ED) discharge instructions is important for ensuring that patients understand their diagnosis, recommendations for treatment, appropriate follow-up, and reasons to return. However, many patients may not fully understand their instructions. Furthermore, some patients may state they understand their instructions even when they do not. We surveyed 75 patients on their perception of their understanding of their ED discharge instructions, and asked them specific questions about the instructions. We also performed a chart review, and examined patients' answers for correlation with the written instructions and medical chart. We then performed a statistical analysis evaluating which patients claimed understanding but who were found to have poor understanding on chart review. Overall, there was no significant correlation between patient self-reported understanding and physician evaluation of their understanding (rho = 0.221, p = 0.08). However, among female patients and patients with less than 4 years of college, there was significant positive correlation between self-report and physician evaluation of comprehension (rho = 0.326, p = 0.04 and rho = 0.344, p = 0.04, respectively), whereas there was no correlation for male patients and those with more than 16 years of education (rho = 0.008, p = 0.9, rho = -0.041, p = 0.84, respectively). Patients' perception of their understanding may not be accurate, especially among men, and those with greater than college education. Identifying which patients say they understand their discharge instructions, but may actually have poor comprehension could help focus future interventions on improving comprehension. PMID- 26358467 TI - Hyponatremia: a challenge for internists. PMID- 26358468 TI - A lectin-based diagnostic system using circulating antibodies to detect cervical intraepithelial neoplasia and cervical cancer. AB - In the present study, we developed serological strategies using immunoglobulin fractions obtained by protein A chromatography to screen for cervical cancer and cervical intraepithelial neoplasia I (CIN I). The reactivities of the immunoglobulins purified from sera of women with normal cytology, CIN I and cervical cancer were compared in enzyme-linked immunosorbent assays (ELISA) and enzyme-linked lectin assays (ELLAs). To capture the immunoglobulins, ELISAs and ELLAs were performed in protein A immobilized microplates. The reactivity of immunoglobulin in ELISA was in the increasing order normal cytology, CIN I and cervical cancer, while that in ELLAs for detecting fucosylation was in the decreasing order normal cytology, CIN I and cervical cancer. It was confirmed that women with CIN I were distinguishable from women with normal cytology or women with cervical cancer in the ELISA or the ELLA for detecting fucosylation with considerable sensitivity and specificity. Women with cervical cancer were also distinguishable from women with normal cytology with high sensitivity (ELISA: 97%, ELLA: 87%) and specificity (ELISA: 69%, ELLA: 72%). Moreover, the logistic regression model of the ELISA and the ELLA discriminated cervical cancer from normal cytology with 93% sensitivity and 93% specificity. These results indicate that the ELISAs and the ELLAs have great potential as strategies for primary screening of cervical cancer and CIN. It is expected that the ELISA and the ELLA can provide new insights to understand systemic changes of serum immunoglobulins during cervical cancer progression. PMID- 26358469 TI - The Prognostic Value of Soluble Intercellular Adhesion Molecule 1 Plasma Level in Children With Acute Lung Injury. AB - OBJECTIVE: The objective of this study was to evaluate the prognostic significance of soluble intercellular adhesion molecule 1 (sICAM-1) measurement in plasma for the prediction of outcome of acute lung injury (ALI) in children that may allow early recognition of critical cases. METHODS: The study was performed as a prospective, controlled cohort study involving 40 children with ALI and 30 healthy children. The plasma level of sICAM-1 was measured at days 1 and 3 of development of ALI for the patient group and measured only once for the control group. C-Reactive protein was measured in both groups on day 1 only. RESULTS: There was significant increase in sICAM-1 in the patient group than in the control group ( P = .001*). The mortality rate reached 55% in children with ALI. The ceased group had significantly higher plasma sICAM-1 levels both at days 1 and 3 than the survived group ( P < .001*), and there was positive correlation between plasma sICAM-1 level and both duration of mechanical ventilation and the death rate, but more significant correlation was observed with plasma sICAM-1 levels at day 3 than day 1. CONCLUSION: Plasma sICAM-1 level served as a good predictor biomarker for both mechanical ventilation duration and the mortality risk in children with ALI. PMID- 26358470 TI - Relative judgment in facial identity perception as revealed by sequential effects. AB - Existing models of facial identity perception often assume that information conveyed by facial stimuli provides the sole basis for identity judgments, largely ignoring the involvement of contextual effects. Capitalizing on sequential effects, the present study investigates whether facial identity is judged relative to a context shaped by stimuli presented in previous trials. When categorizing a sequence of facial identities, our results demonstrated that participants' categorization of current faces varied according to the local sequential context provided by the immediately preceding faces and, to some extent, by the preceding stimuli presented two trials prior to the current trial. Moreover, this variation depended on the relative distance between the preceding and current faces. Notably, the nature of these identity-based sequential effects was qualitatively different between male and female participants. Female participants tended to respond to the current faces with the same category label as on the preceding faces. However, male participants responded with the same label only when the relative distance was small, but responded with a different label when the relative distance was increasingly large. The present study demonstrates that relative information between the preceding and current faces may be used as evidence to inform a judgment. However, this process is multifaceted rather than unitary and depends in part on participant gender. PMID- 26358471 TI - Visibility of speech articulation enhances auditory phonetic convergence. AB - Talkers automatically imitate aspects of perceived speech, a phenomenon known as phonetic convergence. Talkers have previously been found to converge to auditory and visual speech information. Furthermore, talkers converge more to the speech of a conversational partner who is seen and heard, relative to one who is just heard (Dias & Rosenblum Perception, 40, 1457-1466, 2011). A question raised by this finding is what visual information facilitates the enhancement effect. In the following experiments, we investigated the possible contributions of visible speech articulation to visual enhancement of phonetic convergence within the noninteractive context of a shadowing task. In Experiment 1, we examined the influence of the visibility of a talker on phonetic convergence when shadowing auditory speech either in the clear or in low-level auditory noise. The results suggest that visual speech can compensate for convergence that is reduced by auditory noise masking. Experiment 2 further established the visibility of articulatory mouth movements as being important to the visual enhancement of phonetic convergence. Furthermore, the word frequency and phonological neighborhood density characteristics of the words shadowed were found to significantly predict phonetic convergence in both experiments. Consistent with previous findings (e.g., Goldinger Psychological Review, 105, 251-279, 1998), phonetic convergence was greater when shadowing low-frequency words. Convergence was also found to be greater for low-density words, contrasting with previous predictions of the effect of phonological neighborhood density on auditory phonetic convergence (e.g., Pardo, Jordan, Mallari, Scanlon, & Lewandowski Journal of Memory and Language, 69, 183-195, 2013). Implications of the results for a gestural account of phonetic convergence are discussed. PMID- 26358472 TI - Transposition Complex with Aortic Arch Obstruction: Outcomes of One-Stage Repair Over 10 Years. AB - The surgical management of transposition complex with aortic arch obstruction remains technically demanding due to anatomic complexity. Even in the recent surgical era, there are centers that address this anomaly with a staged strategy. This report presents our experiences with a one-stage repair of transposition complexes with aortic arch obstructions more than the last 10 years. Since 2003, 19 patients with a transposition of the great arteries (TGA, 2 patients) or a double outlet of the right ventricle (DORV, 17 patients) and aortic arch obstruction have undergone one-stage repair of their anomalies. The mean age was 6.7 +/- 2.3 days, and the mean body weight was 3.4 +/- 0.3 kg. The 2 patients with TGA exhibited coarctation of the aorta. The 17 patients with DORV all exhibited the Taussig-Bing type. The great artery relationships were anteroposterior in 4 patients (21.1%). The coronary artery anatomies were usual (1LCx; 2R) in 8 patients (42.1%). There were 2 early deaths (10.5%). Seven patients (36.8%) required percutaneous interventions. One patient required re operation for pulmonary valvar stenosis and left pulmonary artery patch angioplasty. The overall survival was 84.2%. The freedom from mortality was 83.5% at 5 years, and the freedom from intervention was 54.4% at 5 years. The one-stage repair of transposition complexes with aortic arch obstructions resulted in an acceptable survival rate and a relatively high incidence of postoperative catheter interventions. Postoperative catheter interventions are highly effective. Transposition complexes combined with aortic arch obstructions can be managed by one-stage repair with good early and midterm results. PMID- 26358473 TI - Impact of Variability in Echocardiographic Interpretation on Assessment of Adequacy of Repair Following Congenital Heart Surgery: A Pilot Study. AB - Technical Performance Score (TPS) is based largely on the presence and magnitude of residual lesions on postoperative echocardiograms; this score correlates with outcomes following repair of congenital heart defects. We evaluated reader variability for echocardiographic components of TPS for complete repair of tetralogy of Fallot (TOF) and arterial switch operation (ASO) in two centers and measured its effect on TPS. Postoperative echocardiograms were evaluated in 67 children (39 TOF and 28 ASO). Two readers (one per center) interpreted each echocardiogram. Reader variability in image quality assessments and measurements was compared using weighted kappa (kappa), percent agreement, and intra-class correlation. TPS class (1 optimal-no residua, 2 adequate-minor residua, 3 inadequate-major residua) was assigned for each echocardiographic review by an independent investigator. The effect of reader interpretation variability on TPS classification was measured. There was strong agreement for TPS between the two readers (kappa = 0.88). The readers were concordant for TPS classes for 57 children (85%) and discordant for classes 2 (minor residua) versus 3 (major residua) in six (9%). Coronary arteries and branch pulmonary arteries were frequently suboptimally visualized. Although inter-reader agreement for TPS was strong, inter-reader variation in echocardiographic interpretations had a small, but important effect on TPS for TOF and ASO, particularly for the distinction between minor and major residua. Further studies of generalizability and reproducibility of TPS and refinement of scoring modules may be needed before it can be used as a tool to assess pediatric cardiac surgical performance and outcomes. PMID- 26358474 TI - Impact of p53 Status on Radiosensitization of Tumor Cells by MET Inhibition Associated Checkpoint Abrogation. AB - Signaling via the MET receptor tyrosine kinase has been implicated in crosstalk with cellular responses to DNA damage. Our group previously demonstrated that MET inhibition in tumor cells with deregulated MET activity results in radiosensitization via downregulation of the ATR-CHK1-CDC25 pathway, a major signaling cascade responsible for intra-S and G2-M cell-cycle arrest following DNA damage. Here we aimed at studying the potential therapeutic application of ionizing radiation in combination with a MET inhibitor, EMD-1214063, in p53 deficient cancer cells that harbor impaired G1-S checkpoint regulation upon DNA damage. We hypothesized that upon MET inhibition, p53-deficient cells would bypass both G1-S and G2-M checkpoints, promoting premature mitotic entry with substantial DNA lesions and cell death in a greater extent than p53-proficient cells. Our data suggest that p53-deficient cells are more susceptible to EMD 1214063 and combined treatment with irradiation than wild-type p53 lines as inferred from elevated gammaH2AX expression and increased cytotoxicity. Furthermore, cell-cycle distribution profiling indicates constantly lower G1 and higher G2-M population as well as higher expression of a mitotic marker p-histone H3 following the dual treatment in p53 knockdown isogenic variant, compared with the parental counterpart. IMPLICATIONS: The concept of MET inhibition-mediated radiosensitization enhanced by p53 deficiency is of high clinical relevance, as p53 is frequently mutated in numerous types of human cancer. The current data point for a therapeutic advantage for an approach combining MET targeting along with DNA-damaging agents for MET-positive/p53-negative tumors. PMID- 26358477 TI - Ischaemic stroke after ST-elevation myocardial infarction. PMID- 26358475 TI - Mycobacterium saopaulense sp. nov., a rapidly growing mycobacterium closely related to members of the Mycobacterium chelonae--Mycobacterium abscessus group. AB - Five isolates of non-pigmented, rapidly growing mycobacteria were isolated from three patients and,in an earlier study, from zebrafish. Phenotypic and molecular tests confirmed that these isolates belong to the Mycobacterium chelonae Mycobacterium abscessus group, but they could not be confidently assigned to any known species of this group. Phenotypic analysis and biochemical tests were not helpful for distinguishing these isolates from other members of the M. chelonae M.abscessus group. The isolates presented higher drug resistance in comparison with other members of the group, showing susceptibility only to clarithromycin. The five isolates showed a unique PCR restriction analysis pattern of the hsp65 gene, 100 % similarity in 16S rRNA gene and hsp65 sequences and 1-2 nt differences in rpoB and internal transcribed spacer (ITS) sequences.Phylogenetic analysis of a concatenated dataset including 16S rRNA gene, hsp65, and rpoB sequences from type strains of more closely related species placed the five isolates together, as a distinct lineage from previously described species, suggesting a sister relationship to a group consisting of M. chelonae, Mycobacterium salmoniphilum, Mycobacterium franklinii and Mycobacterium immunogenum. DNA-DNA hybridization values .70 % confirmed that the five isolates belong to the same species, while values ,70 % between one of the isolates and the type strains of M. chelonae and M. abscessus confirmed that the isolates belong to a distinct species. The polyphasic characterization of these isolates, supported by DNA-DNA hybridization results,demonstrated that they share characteristics with M. chelonae-M. abscessus members, butconstitute a different species, for which the name Mycobacterium saopaulense sp. nov. is proposed. The type strain is EPM10906T (5CCUG 66554T5LMG 28586T5INCQS 0733T). PMID- 26358478 TI - Newly identified RNAs of raspberry leaf blotch virus encoding a related group of proteins. AB - Members of the genus Emaravirus, including Raspberry leaf blotch virus (RLBV), are enveloped plant viruses with segmented genomes of negative-strand RNA, although the complete genome complement for any of these viruses is not yet clear. Currently, wheat mosaic virus has the largest emaravirus genome comprising eight RNAs. Previously, we identified five genomic RNAs for RLBV; here, we identify a further three RNAs (RNA6-8). RNA6-8 encode proteins that have clear homologies to one another, but not to any other emaravirus proteins. The proteins self-interacted in yeast two-hybrid and bimolecular fluorescence complementation (BiFC) experiments, and the P8 protein interacted with the virus nucleocapsid protein (P3) using BiFC. Expression of two of the proteins (P6 and P7) using potato virus X led to an increase in virus titre and symptom severity, suggesting that these proteins may play a role in RLBV pathogenicity; however, using two different tests, RNA silencing suppression activity was not detected for any of the RLBV proteins encoded by RNA2-8. PMID- 26358479 TI - Temperature Prediction Model for Bone Drilling Based on Density Distribution and In Vivo Experiments for Minimally Invasive Robotic Cochlear Implantation. AB - Surgical robots have been proposed ex vivo to drill precise holes in the temporal bone for minimally invasive cochlear implantation. The main risk of the procedure is damage of the facial nerve due to mechanical interaction or due to temperature elevation during the drilling process. To evaluate the thermal risk of the drilling process, a simplified model is proposed which aims to enable an assessment of risk posed to the facial nerve for a given set of constant process parameters for different mastoid bone densities. The model uses the bone density distribution along the drilling trajectory in the mastoid bone to calculate a time dependent heat production function at the tip of the drill bit. Using a time dependent moving point source Green's function, the heat equation can be solved at a certain point in space so that the resulting temperatures can be calculated over time. The model was calibrated and initially verified with in vivo temperature data. The data was collected in minimally invasive robotic drilling of 12 holes in four different sheep. The sheep were anesthetized and the temperature elevations were measured with a thermocouple which was inserted in a previously drilled hole next to the planned drilling trajectory. Bone density distributions were extracted from pre-operative CT data by averaging Hounsfield values over the drill bit diameter. Post-operative [Formula: see text]CT data was used to verify the drilling accuracy of the trajectories. The comparison of measured and calculated temperatures shows a very good match for both heating and cooling phases. The average prediction error of the maximum temperature was less than 0.7 degrees C and the average root mean square error was approximately 0.5 degrees C. To analyze potential thermal damage, the model was used to calculate temperature profiles and cumulative equivalent minutes at 43 degrees C at a minimal distance to the facial nerve. For the selected drilling parameters, temperature elevation profiles and cumulative equivalent minutes suggest that thermal elevation of this minimally invasive cochlear implantation surgery may pose a risk to the facial nerve, especially in sclerotic or high density mastoid bones. Optimized drilling parameters need to be evaluated and the model could be used for future risk evaluation. PMID- 26358476 TI - Short-term heat pre-treatment modulates the release of HMGB1 and pro-inflammatory cytokines in hPDL cells following mechanical loading and affects monocyte behavior. AB - OBJECTIVE: Heat shock proteins (HSP) act as cell-protective molecules that are upregulated upon thermal insult, hypoxia, and ischemia. Such ischemic conditions can be found during tissue remodeling associated with orthodontic tooth movement or trauma when compression forces lead to cell necrosis and subsequent clearance of cellular debris by immune competent cells. Host immune overreaction can result in undesired side effects such as tooth root resorption. Here, we analyzed whether heat pre-treatment would affect the initially catabolic host immune response induced by mechanical loading of human periodontal ligament (hPDL) cells, which represent major constituents of the tooth supporting apparatus involved in the regulation of periodontal remodeling. MATERIALS AND METHODS: Fifth passage hPDL cells were exposed to an elevated temperature of 43 degrees for 1 h prior to mechanical loading. Cell morphology, high mobility group box protein 1 (HMGB1), interleukin (IL)-6, and IL-8 expression were analyzed microscopically and by ELISA. The physiological relevance for monocyte behavior was tested in monocyte adhesion and osteoclast differentiation assays. RESULTS: Short-term heat pre-treatment did not show any visible effect on hPDL cell morphology, but resulted in a significant downregulation of pro-inflammatory cytokines when being additionally loaded mechanically. Supernatants of heat exposed hPDL cell cultures demonstrated a reduced impact on monocyte adhesion and osteoclastic differentiation. CONCLUSIONS: Heat pre-treatment of hPDL cells induces cell-protective mechanisms towards mechanical stress and favors the reduction of cell stress associated effects on monocyte/macrophage physiology. CLINICAL RELEVANCE: These data present the induction of heat shock proteins as a promising treatment option to limit undesired side effects of periodontal remodeling. PMID- 26358480 TI - Continuously Adjustable, Molecular-Sieving "Gate" on 5A Zeolite for Distinguishing Small Organic Molecules by Size. AB - Zeolites/molecular sieves with uniform, molecular-sized pores are important for many adsorption-based separation processes. Pore size gaps, however, exist in the current zeolite family. This leads to a great challenge of separating molecules with size differences at ~0.01 nm level. Here, we report a novel concept, pore misalignment, to form a continuously adjustable, molecular-sieving "gate" at the 5A zeolite pore entrance without sacrificing the internal capacity. Misalignment of the micropores of the alumina coating with the 5A zeolite pores was related with and facilely adjusted by the coating thickness. For the first time, organic molecules with sub-0.01 nm size differences were effectively distinguished via appropriate misalignment. This novel concept may have great potential to fill the pore size gaps of the zeolite family and realize size-selective adsorption separation. PMID- 26358481 TI - The genepi Artemisia species. Ethnopharmacology, cultivation, phytochemistry, and bioactivity. AB - Wormwoods (Artemisia species) from the genepi group are, along with Edelweiss, iconic plants of the Alpine region and true symbols of inaccessibility because of their rarity and their habitat, largely limited to moraines of glaciers and rock crevices. Infusions and liqueurs prepared from genepis have always enjoyed a panacea status in folk medicine, especially as thermogenic agents and remedies for fatigue, dyspepsia, and airway infections. In the wake of the successful cultivation of white genepi (Artemisia umbelliformis Lam.) and the expansion of its supply chain, modern studies have evidenced the occurrence of unique constituents, whose chemistry, biological profile, and sensory properties are reviewed along with the ethnopharmacology, botany, cultivation and conservation strategies of their plant sources. PMID- 26358482 TI - Synthesis and biological activity of polyprenols. AB - The polyprenols and their derivatives are highlighted in this study. These lipid linear polymers of isoprenoid residues are widespread in nature from bacteria to human cells. This review primarily presents the synthesis and biological activities of polyprenyl derivatives. Attention is focused on the synthesis and biological activity of dolichols, polyprenyl ester derivatives and polyprenyl amines. Other polyprenyl derivatives, such as oxides of polyprenols, aromatic polyprenols, polyprenyl bromide and polyprenyl sulphates, are mentioned. It is noted that polyprenyl phosphates and polyprenyl-linked glycosylation have better antibacterial, gene therapy and immunomodulating performance, whereas polyprenyl amines have better for antibacterial and antithrombotic activity. Dolichols, polyprenyl acetic esters, polyprenyl phosphates and polyprenyl-linked glycosylation have pharmacological anti-tumour effects. Finally, the postulated prospect of polyprenols and their derivatives are discussed. Further in vivo studies on the above derivatives are needed. The compatibility of polyprenols and their derivatives with other drugs should be studied, and new preparations of polyprenyl derivatives, such as hydrogel glue and release-controlled drugs, are suggested for future research and development. PMID- 26358483 TI - [Vortioxetine: a new antidepressant to treat depressive episodes]. AB - Vortioxetine is a new antidepressant, which mechanism of action is multimodal, targeting the 5-HT1A, 5-HT1B, 5-HT1D, 5-HT3, 5-HT7 receptors and the serotonin transporter (5-HTT). Its efficacy and safety were assessed in fourteen studies including more than 3700 patients with a major depressive episode and treated with vortioxetine. In short-term studies (8 weeks), vortioxetine is more efficacious than placebo in decreasing depressive symptoms as measured by the MADRS total score, response rate (vortioxetine: 53.2% vs placebo: 35.2%) and remission rate (vortioxetine: 29.2% vs placebo: 19.3%). In a long-term study (52 weeks), vortioxetine is also superior to placebo in preventing relapses and recurrences. Moreover, in second line treatment, after failure of a first line selective serotonin reuptake inhibitor (SSRI) or serotonin norepinephrin reuptake inhibitor (SNRI), vortioxetine is superior to agomelatine in improving depressive symptoms and achieving response and remission. Furthermore, the positive effects of vortioxetine on improvement of cognitive symptoms of major depressive episodes are particularly well established in several clinical trials. The tolerability profile of vortioxetine is favourable. The recommended daily posology of vortioxetine is 10mg/d. Vortioxetine is a new antidepressant drug with a multimodal mechanism of action, well-documented efficacy and safety profiles. PMID- 26358484 TI - [Sequential prescriptions: Arguments for a change of therapeutic patterns in treatment resistant depressions]. AB - Among the therapeutic strategies in treatment of resistant depression, the use of sequential prescriptions is discussed here. A number of observations, initially quite isolated and few controlled studies, some large-scale, have been reported, which showed a definite therapeutic effect of certain requirements in sequential treatment of depression. The Sequenced Treatment Alternatives to Relieve Depression Study (STAR*D) is up to now the largest clinical trial exploring treatment strategies in non psychotic resistant depression in real-life conditions with an algorithm of sequential decision. The main conclusions of this study are the following: after two unsuccessful attempts, the chance of remission decreases considerably. A 12-months follow-up showed that the higher the use of the processing steps were high, the more common the relapses were during this period. The pharmacological differences between psychotropic did not cause clinically significant difference. The positive effect of lithium in combination with antidepressants has been known since the work of De Montigny. Antidepressants allow readjustment of physiological sequence involving different monoaminergic systems together. Studies with tricyclic antidepressant-thyroid hormone T3: in depression, decreased norepinephrine at the synaptic receptors believed to cause hypersensitivity of these receptors. Thyroid hormones modulate the activity of adrenergic receptors. There would be a balance of activity between alpha and beta-adrenergic receptors, depending on the bioavailability of thyroid hormones. ECT may in some cases promote pharmacological response in case of previous resistance, or be effective in preventing relapse. Cognitive therapy and antidepressant medications likely have an effect on different types of depression. We can consider the interest of cognitive therapy in a sequential pattern after effective treatment with an antidepressant effect for treatment of residual symptoms, preventing relapses and recurrences, in antidepressant maintenance. These data support the interest of therapeutic strategies based on evolutionary criteria. Sequential models inspired by statistical methods may incorporate the effects of a future treatment by measuring the current one. PMID- 26358485 TI - [Schooling of patients exhibiting Autism Spectrum Disorders without mental retardation]. AB - INTRODUCTION: Autism Spectrum Disorders belong to Pervasive Development Disorders. Although access to education is recommended by the French National High Authority for Health (HAS), the practice remains limited and the reasons for the low education rate of these children have still not been sufficiently explored in the literature. OBJECTIVE: The main objective of this study was to analyze the links between Autism Spectrum Disorder without mental retardation, psychiatric comorbidity and education. The secondary objective was to analyze the cognitive and contextual factors that could limit educational inclusion. METHOD: Eighty-three autistic patients (3-18years old; 73 males and 10 females) with childhood autism, atypical autism or Asperger's syndrome (criteria from the International Classification of Diseases-10) without mental retardation and in education were assessed at the Alpine Centre for Early Diagnosis of Autism. The sample included 45 subjects with childhood autism, 12 subjects with atypical autism and 26 subjects with Asperger's syndrome. The diagnosis was based on the Autism Diagnostic Interview Revised (ADI-R), in accordance with the recommendations of the HAS, the Autism Diagnostic Observation Schedule (ADOS) and the Wechsler Intelligence Scale for Children, 4th edition (WISC-IV). RESULTS: Our results showed that childhood autism and atypical autism were mainly found in nursery and primary school, whereas Asperger's syndrome was mainly found in secondary school (Chi(2)=18.23; df=6; P<.006). Individuals with childhood autism and atypical autism were more likely to receive the support of a special educational assistant (Chi(2)=15.61; df=2; P<.000) and underwent a higher number of consultations and treatment episodes than those with Asperger's syndrome (Chi(2)=27.83; df=14; P<.015). The cognitive profiles obtained with the WISC-IV also differed: the Verbal Comprehension Index (VCI) and Working Memory Index (WMI) were higher for Asperger's syndrome than for childhood autism and atypical autism (respectively, F=23.11, P<.000; df=2; partial eta(2)=.576 and F=8.06, P<.001; df=2; partial eta(2)=.357). Linear regression showed that the VCI and Processing Speed Index (PSI) were inversely correlated to the number of hours spent with a special educational assistant: the lower these indexes, the greater the amount of time spent with a special educational assistant. No link was found between psychiatric comorbidity, type of psychological and psychiatric treatment, and education. DISCUSSION: The use of special educational assistants seems to be linked to the diagnosis of Autism Spectrum Disorders and neuropsychological functioning, as assessed by WISC-IV, along a continuum that ranges from childhood autism (more needs and deficits) to atypical autism to Asperger's syndrome. The Verbal Comprehension Index (VCI) and the Processing Speed Index (PSI) could be used to evaluate the number of hours of support needed by children and to better target the deficits and specific needs of children without mental retardation who are in education. A study on a larger scale could help to more closely address the question of the cognitive abilities of children with Autism Spectrum Disorder without mental retardation, so as to better help them in their education. PMID- 26358486 TI - Is the Seizure an Unnecessary Component of Electroconvulsive Therapy? A Startling Possibility. PMID- 26358487 TI - The Use of Stimulation Field Models for Deep Brain Stimulation Programming. PMID- 26358488 TI - Recurrence of Migraine With Aura After a 24-year Free Period Following rTMS Treatment for Fibromyalgia Pain. PMID- 26358489 TI - Deep Brain Stimulation in a Dopaminergic Non-responsive Patient With Parkinson's Disease: Case Report and Systematic Review. PMID- 26358490 TI - Anesthesia for Electroconvulsive Therapy--Time for a Review? PMID- 26358491 TI - A Cross Species Approach to Understanding DBS Modulation of Fear. PMID- 26358492 TI - Trigeminal Nerve Stimulation (TNS) for Major Depressive Disorder in Pregnancy: A Case Study. PMID- 26358494 TI - Visual agnosia. AB - Visual agnosia is defined as an impairment of object recognition, in the absence of visual acuity or cognitive dysfunction that would explain this impairment. This condition is caused by lesions in the visual association cortex, sparing primary visual cortex. There are 2 main pathways that process visual information: the ventral stream, tasked with object recognition, and the dorsal stream, in charge of locating objects in space. Visual agnosia can therefore be divided into 2 major groups depending on which of the two streams is damaged. The aim of this article is to conduct a narrative review of the various visual agnosia syndromes, including recent developments in a number of these syndromes. PMID- 26358493 TI - Interaction of dendritic cells and T lymphocytes for the therapeutic effect of Dangguiliuhuang decoction to autoimmune diabetes. AB - In traditional Chinese medicine (TCM), Dangguiliuhuang decoction (DGLHD) is an effective treatment of autoimmune diabetes. Here, we studied potential anti diabetic mechanisms of DGLHD in a non-obese diabetic (NOD) mouse model. In vitro, DGLHD and individual active ingredients enhanced glucose uptake in HepG2 cells, inhibited T lymphocyte proliferation, and suppressed dendritic cells (DCs) function. In vivo, DGLHD significantly inhibited insulitis, delayed the onset and development of diabetes, promoted insulin secretion and sensitivity, and balanced partially normalized Th1 and Th2 cytokines in NOD mice. In addition, DGLHD increased alpha1-antitrypsin (AAT-1), Bcl-2, and CyclinD1, and decreased Bax levels in pancreas, spleen, thymus, DCs, and a NIT-1 cell line, all consistent with protecting and repairing islet beta cell. More detailed studies indicated that DGLHD regulated the maturation and function of DCs, decreased the percentage of merocytic dendritic cells (mcDCs) subset, and increased programmed death ligand-1 (PD-L1) expression in DCs. DGLHD also impeded T lymphocyte proliferation and promoted regulatory T cells (T(regs)) differentiation in vivo. A JAK2-STAT3 dependent pathway was involved in the suppression by DGLHD of interactions between DCs and T lymphocyte. The experiments implicated five active ingredients in specific anti-diabetic actions of DGLHD. The results demonstrated the reasonable composition of the formula. PMID- 26358495 TI - Preservation of within-compound associations after blocked preexposure to two compound flavors. AB - Three experiments investigated the extinction of the within-compound A<->X association established when two compound flavors, AX and BX, are preexposed in blocks (i.e., AX, AX, AX, ... BX, BX, BX). In Experiment 1, a group of rats received preexposure to a block of AX trials followed by a second block of BX trials (AX-BX), while a second group received blocked preexposure to the same stimuli in the opposite order (BX-AX). Subsequently, flavor A was paired with lithium chloride. This conditioning resulted in a similar reduction of consumption of flavor X in both groups. In Experiment 2 four groups of rats received blocked preexposure to AX-BX, AX-B, A-BX, or A-X. After aversive conditioning of X, consumption of A and B was significantly lower for the groups which received these flavors paired with X than for the groups for which these flavors were presented isolated. In Experiment 3 a group of rats was preexposed to a block of SaltX presentations followed by a block of BX presentations (SaltX BX), and a second group received blocked preexposure to (BX-SaltX). After subsequent sodium depletion, consumption of X was high and similar for the SaltX BX and for the BX-SaltX groups. These results indicate that the within-compound association established in the first block of a blocked preexposure is not extinguished when the preexposure phase is concluded. PMID- 26358497 TI - Secondary Amyloid Deposition in Discoid Lupus Erythematosus. PMID- 26358498 TI - Intradermal Lipoblastoma-Like Tumor of the Lip in an Adult Woman. PMID- 26358499 TI - Mast cells and scarring alopecia: Is there a clear pathophysiological relationship? PMID- 26358496 TI - Loose excitation-secretion coupling in astrocytes. AB - Astrocytes play an important housekeeping role in the central nervous system. Additionally, as secretory cells, they actively participate in cell-to-cell communication, which can be mediated by membrane-bound vesicles. The gliosignaling molecules stored in these vesicles are discharged into the extracellular space after the vesicle membrane fuses with the plasma membrane. This process is termed exocytosis, regulated by SNARE proteins, and triggered by elevations in cytosolic calcium levels, which are necessary and sufficient for exocytosis in astrocytes. For astrocytic exocytosis, calcium is sourced from the intracellular endoplasmic reticulum store, although its entry from the extracellular space contributes to cytosolic calcium dynamics in astrocytes. Here, we discuss calcium management in astrocytic exocytosis and the properties of the membrane-bound vesicles that store gliosignaling molecules, including the vesicle fusion machinery and kinetics of vesicle content discharge. In astrocytes, the delay between the increase in cytosolic calcium activity and the discharge of secretions from the vesicular lumen is orders of magnitude longer than that in neurons. This relatively loose excitation-secretion coupling is likely tailored to the participation of astrocytes in modulating neural network processing. PMID- 26358500 TI - Granulomatous Variant of Pigmented Purpura. PMID- 26358501 TI - Novel WT1 Missense Mutations in Han Chinese Women with Premature Ovarian Failure. AB - Premature ovarian failure (POF) is a heterogeneous disease. Though dozens of candidate genes have been identified for the genetic etiology of POF, it is largely unexplained in majority of patients. Recently, Wt1(+/R394W) mice was found to present POF-like phenotype, which indicates that WT1 might be a plausible candidate gene for non-syndromic POF. The coding region of WT1 gene was screened in 384 patients with POF and 6 novel variations were identified, including two missense mutations (p. Pro126Ser in exon1 and p. Arg370His in exon7) and four intronic variants (c.647-27C > T, c.647-13G > C, c.647-13G > A in intron1 and c.950 + 14T > C in intron 4). In vitro experiments showed that both mutant p. Pro126Ser and p. Arg370His repressed the expression of Amh and Cdh1, and induced the expression of Fshr and Cyp19 in mRNA level (P < 0.05). The expression changes of AMH, FSHR, CYP19 and CDH1 were confirmed by western blot. These genes (AMH, FSHR, CYP19 and CDH1) are required for granular cells (GCs) proliferation, differentiation and oocyte-GCs interaction. The novel mutant p. P126S and p. R370H in the WT1 gene potentially impaired GCs differentiation and oocyte-GCs interaction, which might result in loss of follicles prematurely. Therefore, WT1 is a plausible causal gene for POF. PMID- 26358503 TI - De novo sequencing transcriptome of endemic Gentiana straminea (Gentianaceae) to identify genes involved in the biosynthesis of active ingredients. AB - Gentiana straminea is a popular Tibetan medicine that has been used for thousands of years in China to treat various diseases and conditions. Although it has multiple pharmaceutical purposes and important economic plant resource in China, transcriptome and molecular base still known limited. In flowering season, samples were collected from different tissues, using the NGS Illumina. Solexa platform, about 58.85 million sequencing reads were generated and assembled de novo, yielding 78,764 high quality unigenes with an average length of 1090bp. Gene Ontology (GO), KEGG pathway mapping showed that 49,033 of these were identified as putative homologs of annotated sequences in the protein databases. Among them, candidate genes associated with iridoid, flavonoid and anthocyanin were identified. Further the key enzymes involved to iridoid and flavonoid synthesis pathway were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) on different tissues, the flower and root had the higher expression than leaves. In addition, 7591 SSR markers were identified from the unigenes of the G. straminea transcriptome. The foundation of G. straminea provided the important resource for facilitating to study molecular and functional genomics of it and related this species on the Qinghai-Tibet Plateau. PMID- 26358504 TI - Cardiac myosin-binding protein C (MYBPC3) in cardiac pathophysiology. AB - More than 350 individual MYPBC3 mutations have been identified in patients with inherited hypertrophic cardiomyopathy (HCM), thus representing 40-50% of all HCM mutations, making it the most frequently mutated gene in HCM. HCM is considered a disease of the sarcomere and is characterized by left ventricular hypertrophy, myocyte disarray and diastolic dysfunction. MYBPC3 encodes for the thick filament associated protein cardiac myosin-binding protein C (cMyBP-C), a signaling node in cardiac myocytes that contributes to the maintenance of sarcomeric structure and regulation of contraction and relaxation. This review aims to provide a succinct overview of how mutations in MYBPC3 are considered to affect the physiological function of cMyBP-C, thus causing the deleterious consequences observed inHCM patients. Importantly, recent advances to causally treat HCM by repairing MYBPC3 mutations by gene therapy are discussed here, providing a promising alternative to heart transplantation for patients with a fatal form of neonatal cardiomyopathy due to bi-allelic truncating MYBPC3 mutations. PMID- 26358506 TI - Sensory approaches in mental health: A scoping review. AB - BACKGROUND/AIM: Sensory approaches in mental health are designed to assist consumers to regulate physiological and emotional arousal. They have been highlighted as non-invasive, self-directed and empowering interventions that may support recovery-oriented and trauma-informed mental health practice and may assist in efforts to reduce the use of seclusion and restraint. Over recent years, there has been a substantial increase in research in this area. However, there has not yet been any attempt to map and summarise this literature. METHOD: A five-stage scoping review was conducted. Four databases were searched for literature evaluating sensory interventions implemented in mental health settings. RESULTS: A total of 17 studies were included in the final review. A range of sensory approaches was evaluated and a range of outcomes measured. In general, consumers reported reductions in distress associated with engaging in sensory interventions. Results in terms of reduction of seclusion and restraint were mixed, with some studies reporting a decrease, others reporting no change and one reporting an increase. Methodological limitations in the studies reviewed mean that results should be interpreted with caution. CONCLUSIONS: Although there is emerging evidence for the usefulness of sensory approaches in supporting consumers' self-management of distress, there is less evidence for sensory approaches supporting reductions in seclusion and restraint when used in isolation. More research is necessary, but sensory approaches do appear safe and effective. Services wishing to reduce seclusion and restraint should implement sensory approaches in conjunction with other strategies to achieve this important outcome. PMID- 26358505 TI - CCL2 is transcriptionally controlled by the lysosomal protease cathepsin S in a CD74-dependent manner. AB - Cathepsins S (CatS) has been implicated in numerous tumourigenic processes and here we document for the first time its involvement in CCL2 regulation within the tumour microenvironment. Analysis of syngeneic tumours highlighted reduced infiltrating macrophages in CatS depleted tumours. Interrogation of tumours and serum revealed genetic ablation of CatS leads to the depletion of several pro inflammatory chemokines, most notably, CCL2. This observation was validated in vitro, where shRNA depletion of CatS resulted in reduced CCL2 expression. This regulation is transcriptionally mediated, as evident from RT-PCR analysis and CCL2 promoter studies. We revealed that CatS regulation of CCL2 is modulated through CD74 (also known as the invariant chain), a known substrate of CatS and a mediator of NFkB activity. Furthermore, CatS and CCL2 show a strong clinical correlation in brain, breast and colon tumours. In summary, these results highlight a novel mechanism by which CatS controls CCL2, which may present a useful pharmacodynamic marker for CatS inhibition. PMID- 26358502 TI - HSP90AB1: Helping the good and the bad. PMID- 26358507 TI - Brugia malayi cystatin therapeutically ameliorates dextran sulfate sodium-induced colitis in mice. AB - OBJECTIVE: Helminth immunomodulation in the host has been shown to have therapeutic implications in inflammatory bowel diseases. In this study we aimed to evaluate the therapeutic effect of Brugia malayi recombinant cystatin (rBmCys) in a dose-dependent manner on dextran sulfate sodium (DSS)-induced colitis in mice. METHODS: The anti-inflammatory activity of rBmCys on mice peritoneal exudate cells was initially analyzed in vitro. BALB/c mice were fed with 5% DSS for 7 days to induce colitis. The colitis mice were treated intraperitoneally with rBmCys (10, 25 or 50 ug for the three different groups of mice) on days 1, 3 and 5 of the DSS administration. Disease severity was assessed by the disease activity index (DAI) and macroscopic and histopathological scores of colon and myeloperoxidase activity in colonic mucosa. Cytokine profiles were measured in sera and cultured splenocytes of treated mice followed by stimulation with rBmCys. RESULTS: rBmCys showed anti-inflammatory activity in vitro. Treatment of DSS-induced colitis with rBmCys in mice ameliorated the overall disease severity as reflected by a significant reduction in weight loss, the DAI, mucosal edema, colon damage and myeloperoxidase activity of the colonic mucosa. While the mRNA expressions of IFN-gamma, TNF-alpha, interleukin (IL)-5, IL-6 and IL-17 were downregulated, IL-10 expression was upregulated in the splenocytes of colitis mice treated with rBmCys. The amelioration of DSS-induced colitis occurred in a dose-dependent manner. CONCLUSION: The results of this study indicate an anti inflammatory potential of rBmCys and provide evidence for using this protein as a promising therapeutic agent in ulcerative colitis. PMID- 26358508 TI - Arabidopsis TAF1 is an MRE11-interacting protein required for resistance to genotoxic stress and viability of the male gametophyte. AB - Repair of DNA double-strand breaks (DSBs) by recombination pathways is essential for plant growth and fertility. The recombination endonuclease MRE11 plays important roles in sensing and repair of DNA DSBs. Here we demonstrate protein interaction between Arabidopsis MRE11 and the histone acetyltransferase TAF1, a TATA-binding protein Associated Factor (TAF) of the RNA polymerase II transcription initiation factor complex TFIID. Arabidopsis has two TAF1 homologues termed TAF1 and TAF1b and mutant taf1b lines are viable and fertile. In contrast, taf1 null mutations are lethal, demonstrating that TAF1 is an essential gene. Heterozygous taf1+/- plants display abnormal segregation of the mutant allele resulting from defects in pollen tube development, indicating that TAF1 is important for gamete viability. Characterization of an allelic series of taf1 lines revealed that hypomorphic mutants are viable but display developmental defects and reduced plant fertility. Hypersensitivity of taf1 mutants lacking the C-terminal bromodomain to X-rays and mitomycin C, but not to other forms of abiotic stress, established a specific role for TAF1 in plant DNA repair processes. Collectively these studies reveal a function for TAF1 in plant resistance to genotoxic stress, providing further insight into the molecular mechanisms of the DNA damage response in plants. PMID- 26358509 TI - Prevalence and Clinical Determinants of Left Atrial Appendage Thrombus in Patients With Atrial Fibrillation Before Pulmonary Vein Isolation. AB - The CHADS2 score is considered a reliable predictor of stroke/thromboembolism risk in patients with atrial fibrillation (AF). However, thromboembolism can occasionally occur even in patients with AF with low CHADS2 score (CHADS2 score = 0 or 1). To investigate the incidence and predictors of left atrial appendage (LAA) thrombus (LAAT) formation in patients with AF, we studied consecutive 543 Japanese patients with AF who underwent transesophageal echocardiography before pulmonary vein isolation from 2008 to 2012. All patients were treated with anticoagulation therapy with warfarin, and their clinical and echocardiographic characteristics were evaluated. LAATs were observed in 35 (6.4%) of 543 patients, and the prevalence was clearly correlated with the patient's CHADS2 scores. Of 338 patients with low CHADS2 score, LAATs were observed in 7 patients (2.1%). By multivariate analysis, increased left atrial volume (>=50 ml), decreased ejection fraction (<56%), and increased brain natriuretic peptide level (>75 pg/ml) were significantly associated with increased prevalence of LAATs, even in patients with low CHADS2 score. Accordingly, we proposed a new scoring system to predict LAAT (left atrial volume >=50 ml: score 2; ejection fraction <56%: score 1; brain natriuretic peptide >75 pg/ml: score 1). Patients with a score >=2 have a greater risk of LAAT, whereas all patients with score <=1 have no LAATs. Our scoring system is useful for evaluation of the risk of LAAT in patients with AF even with low CHADS2 score. PMID- 26358510 TI - Comparative Effectiveness of Ranolazine Versus Traditional Therapies in Chronic Stable Angina Pectoris and Concomitant Diabetes Mellitus and Impact on Health Care Resource Utilization and Cardiac Interventions. AB - Comparative studies evaluating traditional versus newer antianginal (AA) medications in chronic stable angina pectoris (CSA) on cardiovascular (CV) outcomes and utilization are limited, particularly in patients with diabetes mellitus (DM). Claims data (2008 to 2012) were analyzed using a commercial database. Patients with CSA receiving a beta blocker (BB), calcium channel blocker (CCB), long-acting nitrate (LAN), or ranolazine were identified and followed for 12 months after a change in AA therapy. Patients on traditional AA medications were required to have concurrent sublingual nitroglycerin. Therapy change was defined as adding or switching to another traditional AA medication or ranolazine to identify patients whose angina was inadequately controlled with previous therapy. Four groups were identified (BB, CCB, LAN, or ranolazine users) and matched on relevant characteristics. A DM subset was identified. Logistic regression compared revascularization at 30, 60, 90, 180, and 360 days. Negative binomial regression compared all-cause, CV-, and DM-related (in the DM cohort) health care utilization. A total of 8,008 patients were identified with 2,002 patients in each matched group. Majority were men (mean age 66 years). A subset of 3,724 patients with DM (BB, n = 933; CCB, n = 940; LAN, n = 937; and ranolazine, n = 914) resulted from this cohort. Compared to ranolazine in the overall cohort, traditional AA medication exhibited greater odds for revascularization and higher rates in all-cause outpatient, emergency room visits, inpatient length of stay, and CV-related emergency room visits. In the DM cohort, ranolazine demonstrated similar benefits over traditional AA medication. In conclusion, ranolazine use in patients with inadequately controlled chronic angina is associated with less revascularization and all-cause and CV-related health care utilization compared to traditional AA medication. PMID- 26358511 TI - Surgical Outcomes and Postoperative Prognosis Beyond 10 Years for Double Chambered Right Ventricle. AB - Double-chambered right ventricle (DCRV) is a rare condition. Stenosis of DCRV is progressive, and early surgical intervention is recommended for patients whose symptoms and/or pressure overload of right ventricular (RV) inflow are progressive. However, there are few data regarding the postoperative course of DCRV, and the surgical indications for asymptomatic patients remain to be determined. We retrospectively investigated 38 consecutive patients who were diagnosed with DCRV and underwent surgical intervention from 1981 to 2009. Moreover, we identified 29 patients in whom long-term follow-up transthoracic echocardiographic data were available and investigated the postoperative recurrence of DCRV by evaluating the systolic pressure of RV inflow before, immediately, and in the long term after surgical intervention. The mean follow-up period was 11.0 +/- 8.8 years. There were no deaths and no surgical reinterventions during the long-term follow-up period. Among 29 patients with long-term follow-up echocardiographic data, there was no recurrence of DCRV. In these patients, the systolic pressure of RV inflow by echocardiography before, immediately, and long-term after surgical intervention was 80 +/- 26, 30 +/- 11, and 25 +/- 6 mm Hg, respectively. In conclusion, the surgical outcomes and postoperative prognosis beyond 10 years of DCRV are favorable, and neither recurrence of DCRV nor fatal arrhythmias develop during the long-term follow-up period. PMID- 26358512 TI - Clinical and Echocardiographic Features of Mitral Annular Calcium in Patients Aged <=50 Years. AB - Data regarding characteristics of young patients with mitral annular calcification (MAC) and its associations with other cardiovascular risk factors are scarce. Hence, we sought to characterize patients aged <50 years with MAC and to examine whether in these patients, MAC is also associated with cardiovascular risk factors. Consecutive patients who underwent an echocardiographic study were prospectively entered into a database. The database included clinical, laboratory, and echocardiographic parameters. The present study included 56 patients aged <50 years with a diagnosis of MAC. The mean age was 44.2 +/- 6.9 years with a male-to-female ratio of 2.5:1. The prevalence of cardiovascular risk factors (30 patients [53%] hypertension, 17 patients [30%] diabetes mellitus, 24 patients [43%] dyslipidemia, 22 patients [39%] smoking) and established cardiovascular disease (22 patients [39%] coronary artery disease, 11 patients [19%] previous stroke) was substantially higher than expected for this age group. Twenty-nine patients (52%) had chronic kidney disease. Of these, 18 patients (62%) had end-stage kidney disease and 7 patients (24%) underwent renal transplantation. Fourteen patients (25%) and 3 patients (5%) had moderate or severe mitral regurgitation and mitral stenosis, respectively. Aortic valve disease was present in 37 patients (66%). Moderate or severe left ventricular dysfunction and left ventricular hypertrophy were identified in 9 patients (16%) and 31 patients (56%), respectively. In conclusion, the detection of MAC in a young patient should be regarded as a marker of atherosclerotic disease, chronic kidney disease, and aortic valve disease. PMID- 26358513 TI - Endofin, a novel BMP-SMAD regulator of the iron-regulatory hormone, hepcidin. AB - BMP-SMAD signalling plays a crucial role in numerous biological processes including embryonic development and iron homeostasis. Dysregulation of the iron regulatory hormone hepcidin is associated with many clinical iron-related disorders. We hypothesised that molecules which mediate BMP-SMAD signalling play important roles in the regulation of iron homeostasis and variants in these proteins may be potential genetic modifiers of iron-related diseases. We examined the role of endofin, a SMAD anchor, and show that knockdown of endofin in liver cells inhibits basal and BMP-induced hepcidin expression along with other BMP regulated genes, ID1 and SMAD7. We show for the first time, the in situ interaction of endofin with SMAD proteins and significantly reduced SMAD phosphorylation with endofin knockdown, suggesting that endofin modulates hepcidin through BMP-SMAD signalling. Characterisation of naturally occurring SNPs show that mutations in the conserved FYVE domain result in mislocalisation of endofin, potentially affecting downstream signalling and modulating hepcidin expression. In conclusion, we have identified a hitherto unrecognised link, endofin, between the BMP-SMAD signalling pathway, and the regulation of hepcidin expression and iron homeostasis. This study further defines the molecular network involved in iron regulation and provides potential targets for the treatment of iron-related disorders. PMID- 26358514 TI - A forward-striking technique for reducing fracture gaps during intramedullary nailing: A technical note with clinical results. AB - INTRODUCTION: A residual postoperative fracture gap between major bone fragments following intramedullary nailing of long-bone fractures is recognised as one of the major risk factors for delayed union and non-union. The most common method for reducing a fracture gap after nail insertion is through application of the backstroke technique. We introduce forward-striking as a new and simple technique that can be used to reduce fracture gaps during cephalomedullary or intramedullary nailing. PATIENTS AND METHODS: The forward-striking technique was used in 20 patients with subtrochanteric or femoral shaft fractures and three patients with tibial shaft fractures who underwent cephalomedullary or intramedullary nailing at two university teaching hospitals between February 2013 and March 2014. RESULTS: Bone union was achieved in all cases, with a mean time of 5.7 months (range, 3-9 months). No major complications, including, non-union, implant failure, or infection, were encountered during the follow-up period. CONCLUSION: A forward-striking technique is simple, convenient, and highly efficient in terms of reducing fracture gaps during cephalomedullary or intramedullary nailing. The advantage of this technique is that it carries no risk of deforming the proximal interlocking screw, prevents excessive protrusion of the nail, and enables the lag screw to be placed into the optimal lag screw position relative to the femoral head at the time of cephalomedullary nailing. The forward-striking technique is particularly useful if no compression screw system is available. PMID- 26358515 TI - Combat related vascular injuries: Dutch experiences from a role 2 MTF in Afghanistan. AB - BACKGROUND: In a combat environment, major vascular trauma endures as the leading cause of death. The Dutch role 2 Medical Treatment Facility (MTF), provided supportive care during the mission in Uruzgan, Afghanistan. Aim of this study was to conduct detailed analysis of the admitted major haemorrhages (vascular injuries) and to compare our findings with NATO coalition partners. METHODS: Retrospective, descriptive study. Participants eligible for this study came from the role 2 MTF admission database, where they fitted the criteria 'Major haemorrhage (class 2 haemorrhage or more according to the ATLS((r)) classification) between 2006 and 2010'. Results were contrasted with studies from coalition partners. RESULTS: The query revealed 194 casualties sustaining 208 central (60% abdominal, 40% thoracic/neck), and 99 extremity major haemorrhages leading to 1.6 major haemorrhages per casualty. Survival was significantly better (p<0.05) in the peripheral vascular injuries cohort (96% versus 72%). Primary amputation was needed in 73/84 of lower, and in 8/15 of upper extremity major haemorrhages. Vascular repair or vascular Damage Control Surgery techniques (e.g. shunting) were used in 19/84 cases in the lower, and 7/15 in the upper extremity cohort, with a success rate of 69.2 percent. Amputation rates of coalition partners, using different inclusion and exclusion criteria, ranged from 5 to 60 percent. CONCLUSIONS: Only in a few cases genuine peripheral vascular surgery was needed (<1%). This limited number of reconstructions does not demonstrate the need for extensive skills in all areas of vascular surgery. Achieved success rate until discharge was almost 70%. Vascular damage control surgery seems effective as initial limb saving skill in a role 2 MTF. The difference in usage of definitions concerning vascular injuries in current literature warrants further assessment. For optimal analysis there is need for detailed (NATO wide) registration with uniform definitions for vascular injuries. LEVEL OF EVIDENCE: Level IV--Epidemiologic study. PMID- 26358516 TI - Establishing a definitive airway in the trauma patient by novice intubators: A randomised crossover simulation study. AB - BACKGROUND: Establishing a definitive airway, defined as a tube placed in the trachea with cuff inflated below the vocal cords, is standard of care in pre hospital airway management of the trauma patient. However, in this setting, and using manual in-line stabilisation of the neck, success rate of intubation by inexperience providers is suboptimal. The use of supraglottic airway devices that allow blind tracheal intubation has been suggested as an alternative method by the Advanced Trauma Life Support (ATLS) programme of the American College of Surgeons. We aimed to compare intubation with the standard intubation technique (direct laryngoscopy [DL]) with blind intubation through an intubating-laryngeal mask airway (I-LMA) during manual in-line stabilisation of the neck. MATERIALS AND METHODS: A randomised, crossover manikin study was performed with 29 emergency medical technicians undergoing training for paramedic status. Outcome measures were success rate in one intubation attempt, duration of intubation, and assessment of ease-of-use. RESULTS: Study subjects had a higher success rate of tracheal intubation with I-LMA than with DL (27/29 vs. 18/29, p<0.025), and I-LMA was assessed as easier to use (4 vs. 3, p<0.0001). Longer duration of intubation was found with I-LMA compared to DL (54.2 vs. 42.8s, p<0.002). Success rate of correct placement of I-LMA within the airway was 28/29 (96.5%). Time to achieve correct placement of I-LMA within the airway was shorter than duration of tracheal intubation with DL (26.9 vs. 42.8s, p<0.0001). CONCLUSIONS: Novice intubators had a higher success rate of intubation with I-LMA than with DL, but duration of intubation was longer with I-LMA. Time to achieve correct placement of I-LMA within the airway was shorter than duration of tracheal intubation with DL. Findings of this simulation study suggest that in the presence of manual in line stabilisation of the neck, I-LMA-guided intubation is the preferred technique for novice intubators. PMID- 26358517 TI - Thoracic Trauma Severity score on admission allows to determine the risk of delayed ARDS in trauma patients with pulmonary contusion. AB - BACKGROUND: Pulmonary contusion is a major risk factor of acute respiratory distress syndrome (ARDS) in trauma patients. As this complication may appear after a free interval of 24-48 h, detection of patients at risk is essential. The main objective of this study was to assess the performance of the Thoracic Trauma Severity (TTS) score upon admission in predicting delayed ARDS in blunt trauma patients with pulmonary contusion. METHODS: All blunt thoracic trauma patients admitted consecutively to our trauma centre between January 2005 and December 2009 were retrospectively included if they presented a pulmonary contusion on the admission chest computed tomography scan. Main outcome measure was the presence of moderate or severe ARDS (PaO2/FiO2 ratio<=200) for 48 h or more. The global ability of the TTS score to predict ARDS was studied by ROC curves with a threshold analysis using a grey zone approach. RESULTS: Of 329 patients studied (75% men, mean age 36.9 years [SD 17.8 years], mean Injury Severity Score 21.7 [SD 16.0]), 82 (25%) presented with ARDS (mean lowest PaO2/FiO2 ratio of 131 [SD 34]). The area under the ROC curves for the TTS score in predicting ARDS was 0.82 (95% CI 0.78-0.86) in the overall population. TTS scores between 8 and 12 belonged to the inconclusive grey zone. A TTS score of 13-25 was found to be independent risk factors of ARDS (OR 25.8 [95% CI 6.7-99.6] P<0.001). CONCLUSIONS: An extreme TTS score on admission accurately predicts the occurrence of delayed ARDS in blunt thoracic trauma patients affected by pulmonary contusion. This simple score could guide early decision making and management for a non-negligible proportion of this specific population. PMID- 26358518 TI - Optimization of the CULTEX((r)) radial flow system for in vitro investigation of lung damaging agents. AB - Exposure of the respiratory tract to airborne particles is gaining more and more importance due to the ubiquitous application of these particles in the field of industry, pharmacy and in daily life. Remarkably, the toxic properties and the underlying pathomechanisms with regard to inhalable substances have been insufficiently investigated so far. Thus, the EU Chemicals Regulation demands toxicological data (including the identification of potential inhalation hazards) for all chemicals placed on the market until 2018 (REACH). This requires extensive, technically complex and expensive inhalation toxicology studies that are usually generated in animal experiments. However, the legislation demands the consideration of the "3Rs" principle. Thus, in vitro-based test systems for the assessment of pulmonary toxicity are required. One promising approach to assess acute pulmonary toxicity of airborne particles is the CULTEX((r)) RFS methodology that allows exposure of human lung epithelial cells at the air-liquid interface mimicking the alveolar situation. A prevalidation study showed the general applicability of this method. However, the clean air exposure group, which served as unexposed controls, exhibited some variations with regard to cell viability compared to the incubator control group. The aim of this study was therefore the identification of the possible causes and the improvement of methodological aspects. Several parameters including the general workflow, adjustment of airflow parameters, and cleaning procedures were investigated and adapted. Finally, our results showed the successful optimization of the CULTEX((r)) RFS methodology for clean air exposure of A549 cells. However, although viability data in incubator controls and clean air exposures were equal, a distinct difference in cell morphology was observed that required further optimization. Additional experiments identified that open-wall cell culture inserts with a 2-fold pore density were found to be superior compared to the standard inserts and thus the deciding factor for the improvement of cell morphology. The presented findings are an important step in providing the CULTEX((r)) RFS methodology as a promising alternative method to current in vivo testing in inhalation toxicology. PMID- 26358519 TI - Hexachlorobenzene promotes angiogenesis in vivo, in a breast cancer model and neovasculogenesis in vitro, in the human microvascular endothelial cell line HMEC 1. AB - Exposure to environmental pollutants may alter proangiogenic ability and promotes tumor growth. Hexachlorobenzene (HCB) is an organochlorine pesticide found in maternal milk and in lipid foods, and a weak ligand of the aryl hydrocarbon receptor (AhR). HCB induces migration and invasion in human breast cancer cells, as well as tumor growth and metastasis in vivo. In this study, we examined HCB action on angiogenesis in mammary carcinogenesis. HCB stimulates angiogenesis and increases vascular endothelial growth factor (VEGF) expression in a xenograft model with the human breast cancer cell line MDA-MB-231. Human microvascular endothelial cells HMEC-1 exposed to HCB (0.005, 0.05, 0.5 and 5MUM) showed an increase in cyclooxygenase-2 (COX-2) and VEGF protein expression involving AhR. In addition, we found that HCB enhances VEGF-Receptor 2 (VEGFR2) expression, and activates its downstream pathways p38 and ERK1/2. HCB induces cell migration and neovasculogenesis in a dose-dependent manner. Cells pretreatment with AhR, COX-2 and VEGFR2 selective inhibitors, suppressed these effects. In conclusion, our results show that HCB promotes angiogenesis in vivo and in vitro. HCB-induced cell migration and tubulogenesis are mediated by AhR, COX-2 and VEGFR2 in HMEC-1. These findings may help to understand the association among HCB exposure, angiogenesis and mammary carcinogenesis. PMID- 26358520 TI - Biomarkers in the early diagnosis of sepsis: the quest continues. PMID- 26358521 TI - Graft-versus-host disease after orthotopic liver transplantation: multivariate analysis of risk factors. AB - Graft-versus-host disease (GVHD) is a rare, fatal complication following orthotopic liver transplantation (OLT). To date, several risk factors have been proposed, but reports on these factors have been inconclusive. This is a retrospective, case-control study of prospectively collected data from 2775 OLTs performed at our institution. Eight cases of GVHD after OLT were diagnosed on the basis of the patient's clinical characteristics, and the findings were confirmed with skin and colonic biopsies. Each case was matched to three controls based on the diagnosis of liver disease, recipient's age, and blood group. Univariate and multivariate analyses were performed to identify risk factors associated with the development of GVHD after OLT. The univariate and multivariate analyses identified two main risk factors associated with development of GVHD in OLT recipients, a difference between recipient and donor age of >20 yr, and any human leukocyte antigen class I matches. Taking these two risk factors into consideration while matching prospective donors and recipients may reduce further incidence of GVHD in OLT patients. However, further studies are recommended to validate these findings. PMID- 26358522 TI - Molecular authentication and quantitative analysis of Sarcandra glabra and adulterated chloranthus products using SNP markers. AB - BACKGROUND: Sarcandra glabra (Thunb.) Nakai is one of the most popular and valuable plant species in the oriental medicinal herb market. Chloranthus (Chloranthaceae) species are the most widely used adulterants, but they are known to have hepatotoxicity effects and different medicinal values. OBJECTIVE: The aim of this study is to develop a robust and accurate DNA marker for the qualitative and quantitative analyses of their products. MATERIALS AND METHODS: Four single nucleotide polymorphism (SNP) sites specific to Sarcandra glabra, Chloranthus spicatus, Chloranthus serratus and Chloranthus henryi were exploited from the trnL-F region in chloroplast DNA, which have a higher copy number in the products than the nuclear DNA. Based on the SNP sites, specific primers were designed to identify the products of Sarcandra glabra, Chloranthus spicatus, Chloranthus serratus and Chloranthus henryi in mixed solutions via multiplexed PCR. The primers were also used to quantitatively analyse the ratio of chloroplast DNA in the mixed products using real-time PCR. RESULTS: The established multiplexed-PCR and real-time PCR methods were determined to be effective for the authentication and relative quantitative assessments of the products of Sarcandra glabra, its adulterants, and their mixtures. CONCLUSION: We therefore present an effective method for monitoring the quality of these products. PMID- 26358523 TI - Integrative proteomic and gene expression analysis identify potential biomarkers for adjuvant trastuzumab resistance: analysis from the Fin-her phase III randomized trial. AB - Trastuzumab is a remarkably effective therapy for patients with human epidermal growth factor receptor 2 (HER2)--positive breast cancer (BC). However, not all women with high levels of HER2 benefit from trastuzumab. By integrating mRNA and protein expression data from Reverse-Phase Protein Array Analysis (RPPA) in HER2 positive BC, we developed gene expression metagenes that reflect pathway activation levels. Next we assessed the ability of these metagenes to predict resistance to adjuvant trastuzumab using gene expression data from two independent datasets.10 metagenes passed external validation (false discovery rate [fdr] < 0.05) and showed biological relevance with their pathway of origin. These metagenes were further screened for their association with trastuzumab resistance. An association with trastuzumab resistance was observed and validated only for the AnnexinA1 metagene (ANXA1). In the randomised phase III Fin-her study, tumours with low levels of the ANXA1 metagene showed a benefit from trastuzumab (multivariate: hazard ratio [HR] for distant recurrence = 0.16[95%CI 0.05-0.5]; p = 0.002; fdr = 0.03), while high expression levels of the ANXA1 metagene were associated with a lack of benefit to trastuzmab (HR = 1.29[95%CI 0.55-3.02]; p = 0.56). The association of ANXA1 with trastuzumab resistance was successfully validated in an independent series of subjects who had received trastuzumab with chemotherapy (Log Rank; p = 0.01).In conclusion, in HER2 positive BC, some proteins are associated with distinct gene expression profiles. Our findings identify the ANXA1metagene as a novel biomarker for trastuzumab resistance. PMID- 26358524 TI - Cycloartenyl Ferulate Inhibits Paraquat-Induced Apoptosis in HK-2 Cells With the Involvement of ABCC1. AB - Nephrotoxicity induced by chemicals such as paraquat (PQ) is a common clinical phenomenon; therefore, searching for drugs with renal protective effect is of a great practical significance. Our previous investigation found that cycloartenyl ferulate (CF) can antagonize the cytotoxic effect of PQ, and recent studies also revealed a variety of bioactivities of CF. However, specific molecular mechanisms underlying the protective effect of CF have not been explored yet. HPLC detection of PQ content indicated that CF reduced PQ accumulation in HK-2 cells and thereby improved cell survival. Western blot results showed that both PQ and CF did not affect the expression of ABCB1; however, while PQ suppressed the expression of ABCC1, CF upregulated ABCC1 expression and thereby reversed the inhibitory effect of PQ on ABCC1 expression. Meanwhile, HK-2 cells did not express ABCG2. When the expression of ABCC1 was knocked down with siRNA, the inhibitory effect of CF on intracellular PQ accumulation was blocked. Further flow cytometric analysis showed that while PQ significantly induced the appearance of sub-G1 apoptotic peak in cells, CF evidently inhibited apoptosis. TUNEL-DAPI double-staining also detected that PQ significantly induced the occurrence of DNA fragmentation in cells, whereas CF effectively inhibited the effect of PQ. Further results showed that ABCC1 siRNA effectively abolished the protective effect of CF on PQ-induced apoptosis. Taken together, these data demonstrated that in HK-2 cells, CF could antagonize PQ-induced toxicity with the involvement of regulatiion of ABCC1 protein expression, which provides a new strategy for treatments of nephrotoxicity. PMID- 26358525 TI - Occupational therapy practice in acute physical hospital settings: Evidence from a scoping review. AB - BACKGROUND/AIM: Increased accountability and growing fiscal limitations in global health care continue to challenge how occupational therapy practices are undertaken. Little is known about how these changes affect current practice in acute hospital settings. This article reviews the relevant literature to further understanding of occupational therapy practice in acute physical hospital settings. METHOD: A scoping review of five electronic databases was completed using the keywords Occupational therapy, acute hospital settings/acute physical hospital settings, acute care setting/acute care hospital setting, general medicine/general medical wards, occupational therapy service provision/teaching hospitals/tertiary care hospitals. Criteria were applied to determine suitability for inclusion and the articles were analysed to uncover key themes. RESULTS: In total 34 publications were included in the review. Analysis of the publications revealed four themes: (1) Comparisons between the practice of novice and experienced occupational therapists in acute care (2) Occupational therapists and the discharge planning process (3) Role of occupation in the acute care setting and (4) Personal skills needed and organisation factors affecting acute care practice. CONCLUSION: The current literature has highlighted the challenges occupational therapists face in practicing within an acute setting. Findings from this review enhance understanding of how occupational therapy department managers and educators can best support staff that practise in acute hospital settings. PMID- 26358526 TI - Circulating tumor cells and cholangiocarcinoma. PMID- 26358528 TI - Optimal nonlinear information processing capacity in delay-based reservoir computers. AB - Reservoir computing is a recently introduced brain-inspired machine learning paradigm capable of excellent performances in the processing of empirical data. We focus in a particular kind of time-delay based reservoir computers that have been physically implemented using optical and electronic systems and have shown unprecedented data processing rates. Reservoir computing is well-known for the ease of the associated training scheme but also for the problematic sensitivity of its performance to architecture parameters. This article addresses the reservoir design problem, which remains the biggest challenge in the applicability of this information processing scheme. More specifically, we use the information available regarding the optimal reservoir working regimes to construct a functional link between the reservoir parameters and its performance. This function is used to explore various properties of the device and to choose the optimal reservoir architecture, thus replacing the tedious and time consuming parameter scannings used so far in the literature. PMID- 26358527 TI - Colorectal cancer screening of immigrants to Italy. Figures from the 2013 National Survey. AB - BACKGROUND: Colorectal cancer screening programmes in Italy invite 50-69-year-old residents for a faecal immunochemical test every two years, regardless of their citizenship. METHODS: The 2013 National Survey on Italian colorectal cancer screening programmes compared immigrants born in low- or middle-income countries with subjects who were born in Italy, by collecting aggregated data on compliance, faecal immunochemical test results, compliance with colonoscopy, detected lesions and stage at diagnosis separately for Italians and immigrants. RESULTS: Overall, 85 screening programmes invited 3,292,451 subjects, of whom 192,629 had been born abroad (5.9%). Compliance with invitation was lower in immigrants (34.3% vs. 51.3% in Italians), with p<0.001. Compliance was higher in females, regardless of the country of birth, in the youngest age group of immigrants but in the oldest of Italians. Immigrants showed a borderline excess of standardised faecal immunochemical test positivity rate at first screening (5.4% vs. 5.1% in Italians, p=0.05) and a significant excess at repeat screenings (4.8% vs. 4.4%, p=0.002). The detection rates for carcinoma and advanced adenomas were lower in immigrants than in Italians at first screening (respectively 1.340/00 vs. 1.620/00 and 8.410/00 vs. 9.250/00) - although the differences were not statistically significant - but not at repeat screening (respectively 1.060/00 vs. 0.980/00 and 6.900/00 vs. 6.790/00). CONCLUSIONS: Migrants showed a lower compliance with screening than Italians. The prevalence of neoplasia was lower at first screening and similar to the Italians' at repeat screenings. PMID- 26358529 TI - Depth-resolved rhodopsin molecular contrast imaging for functional assessment of photoreceptors. AB - Rhodopsin, the light-sensing molecule in the outer segments of rod photoreceptors, is responsible for converting light into neuronal signals in a process known as phototransduction. Rhodopsin is thus a functional biomarker for rod photoreceptors. Here we report a novel technology based on visible-light optical coherence tomography (VIS-OCT) for in vivo molecular imaging of rhodopsin. The depth resolution of OCT allows the visualization of the location where the change of optical absorption occurs and provides a potentially accurate assessment of rhodopsin content by segmentation of the image at the location. Rhodopsin OCT can be used to quantitatively image rhodopsin distribution and thus assess the distribution of functional rod photoreceptors in the retina. Rhodopsin OCT can bring significant impact into ophthalmic clinics by providing a tool for the diagnosis and severity assessment of a variety of retinal conditions. PMID- 26358530 TI - A microRNA allele that emerged prior to apple domestication may underlie fruit size evolution. AB - The molecular genetic mechanisms underlying fruit size remain poorly understood in perennial crops, despite size being an important agronomic trait. Here we show that the expression level of a microRNA gene (miRNA172) influences fruit size in apple. A transposon insertional allele of miRNA172 showing reduced expression associates with large fruit in an apple breeding population, whereas over expression of miRNA172 in transgenic apple significantly reduces fruit size. The transposon insertional allele was found to be co-located with a major fruit size quantitative trait locus, fixed in cultivated apples and their wild progenitor species with relatively large fruit. This finding supports the view that the selection for large size in apple fruit was initiated prior to apple domestication, likely by large mammals, before being subsequently strengthened by humans, and also helps to explain why signatures of genetic bottlenecks and selective sweeps are normally weaker in perennial crops than in annual crops. PMID- 26358531 TI - An optimized proportional-derivative controller for the human upper extremity with gravity. AB - When Functional Electrical Stimulation (FES) is used to restore movement in subjects with spinal cord injury (SCI), muscle stimulation patterns should be selected to generate accurate and efficient movements. Ideally, the controller for such a neuroprosthesis will have the simplest architecture possible, to facilitate translation into a clinical setting. In this study, we used the simulated annealing algorithm to optimize two proportional-derivative (PD) feedback controller gain sets for a 3-dimensional arm model that includes musculoskeletal dynamics and has 5 degrees of freedom and 22 muscles, performing goal-oriented reaching movements. Controller gains were optimized by minimizing a weighted sum of position errors, orientation errors, and muscle activations. After optimization, gain performance was evaluated on the basis of accuracy and efficiency of reaching movements, along with three other benchmark gain sets not optimized for our system, on a large set of dynamic reaching movements for which the controllers had not been optimized, to test ability to generalize. Robustness in the presence of weakened muscles was also tested. The two optimized gain sets were found to have very similar performance to each other on all metrics, and to exhibit significantly better accuracy, compared with the three standard gain sets. All gain sets investigated used physiologically acceptable amounts of muscular activation. It was concluded that optimization can yield significant improvements in controller performance while still maintaining muscular efficiency, and that optimization should be considered as a strategy for future neuroprosthesis controller design. PMID- 26358532 TI - [Use of physical restraint in geriatric nursing homes in the metropolitan area of Monterrey, Mexico]. PMID- 26358533 TI - Motivational interviewing to improve self-care for patients with chronic heart failure: MITI-HF randomized controlled trial. AB - OBJECTIVE: The purpose of this study was to test the efficacy of a tailored motivational interviewing (MI) intervention versus usual care for improving HF self-care behaviors, physical HF symptoms and quality of life. METHODS: This is a single-center, randomized controlled trial. Participants were enrolled in the hospital. Immediately after discharge, those in the intervention group received a single home visit and 3-4 follow-up phone calls by a nurse over 90 days. RESULTS: A total of 67 participants completed the study (mean age 62+/-12.8 years), of which 54% were African American, 30% were female, 84% had class III/IV symptoms, and 63% were educated at a high school level or less. There were no differences between the groups in self-care maintenance, self-care confidence, physical HF symptoms, or quality of life at 90 days. CONCLUSION: Patients who received the MI intervention had significant and clinically meaningful improvements in HF self care maintenance over 90 days that exceeded that of usual care. PRACTICE IMPLICATIONS: These data support the use of a nurse-led MI intervention for improving HF self-care. Identifying methods to improve HF self-care may lead to improved clinical outcomes. PMID- 26358534 TI - Increasing collective efficacy for physical activity: Design and rationale of Moms UNITE for Health. AB - BACKGROUND: Mothers are a population that engages in low levels of physical activity due to unique barriers to physical activity. As such, there is a need to develop and implement physical activity interventions for mothers that can be delivered in community settings. The objective of this article is to describe the Moms UNITE (Using Networks to Increase Togetherness and Efficacy) for Health walking intervention. This intervention, based on social cognitive theory, is designed to compare a collective efficacy enhanced intervention to a standard intervention for increasing physical activity and secondary outcomes. METHODS: In this 6-week, randomized controlled trial, mothers will be assigned to either the standard or intervention (collective efficacy) group. Both groups will receive the same walking intervention and an evidence-based health education program. Strategies and messages focusing on building collective efficacy will be used in the intervention group. Data will be collected at baseline, post-intervention, and follow-up (after a 3 month no-intervention period) using a mixed methods approach. RESULTS: Quantitative data will include anthropometric measurements, objective physical activity, and questionnaires assessing self- and collective efficacy. Post-intervention focus groups and weekly process evaluation surveys will describe participants' experiences within the program. CONCLUSIONS: This paper will serve as a theoretical framework for researchers and public health practitioners to develop and implement community-based walking programs for mothers. PMID- 26358535 TI - Fe en Accion/Faith in Action: Design and implementation of a church-based randomized trial to promote physical activity and cancer screening among churchgoing Latinas. AB - OBJECTIVES: To describe both conditions of a two-group randomized trial, one that promotes physical activity and one that promotes cancer screening, among churchgoing Latinas. The trial involves promotoras (community health workers) targeting multiple levels of the Ecological Model. This trial builds on formative and pilot research findings. DESIGN: Sixteen churches were randomly assigned to either the physical activity intervention or cancer screening comparison condition (approximately 27 women per church). In both conditions, promotoras from each church intervened at the individual- (e.g., beliefs), interpersonal- (e.g., social support), and environmental- (e.g., park features and access to health care) levels to affect change on target behaviors. MEASUREMENTS: The study's primary outcome is min/wk of moderate-to-vigorous physical activity (MVPA) at baseline and 12 and 24 months following implementation of intervention activities. We enrolled 436 Latinas (aged 18-65 years) who engaged in less than 250 min/wk of MVPA at baseline as assessed by accelerometer, attended church at least four times per month, lived near their church, and did not have a health condition that could prevent them from participating in physical activity. Participants were asked to complete measures assessing physical activity and cancer screening as well as their correlates at 12- and 24-months. SUMMARY: Findings from the current study will address gaps in research by showing the long term effectiveness of multi-level faith-based interventions promoting physical activity and cancer screening among Latino communities. PMID- 26358537 TI - Heart-lung vs. double-lung transplantation for idiopathic pulmonary arterial hypertension. AB - Patients with idiopathic pulmonary arterial hypertension (IPAH) have improved survival after heart-lung transplantation (HLT) and double-lung transplantation (DLT). However, the optimal procedure for patients with IPAH undergoing transplantation remains unclear. We hypothesized that critically ill IPAH patients, defined by admission to the intensive care units (ICU), would demonstrate improved survival with HLT vs. DLT. All adult IPAH patients (>18 yr) in the Scientific Registry of Transplant Recipients (SRTR) database, who underwent either HLT or DLT between 1987 and 2012, were included. Baseline characteristics, survival, and adjusted survival were compared between the HLT and DLT groups. Similar analyses were performed for the subgroups as defined by the recipients' hospitalization status. A total of 928 IPAH patients (667 DLT, 261 HLT) were included in this analysis. The HLT recipients were younger, more likely to be admitted to the ICU, and have had their transplant in previous eras. Overall, the adjusted survivals after HLT or DLT were similar. For recipients who were hospitalized in the ICU, DLT was associated with worse outcomes (HR 1.827; 95% CI 1.018-3.279). In IPAH patients, the overall survival after HLT or DLT is comparable. HLT may provide improved outcomes in critically ill IPAH patients admitted to the ICU at time of transplantation. PMID- 26358536 TI - Design of the FRESH study: A randomized controlled trial of a parent-only and parent-child family-based treatment for childhood obesity. AB - Approximately 1 out of 3 children in the United States is overweight or obese. Family-based treatment (FBT) is considered the gold-standard treatment for childhood obesity, but FBT is both staff and cost intensive. Therefore, we developed the FRESH (Family, Responsibility, Education, Support, & Health) study to evaluate the effectiveness of intervening with parents, without child involvement, to facilitate and improve the child's weight status. Targeting parents directly in the treatment of childhood obesity could be a promising approach that is developmentally appropriate for grade-school age children, highly scalable, and may be more cost effective to administer. The current paper describes the FRESH study which was designed to compare the effectiveness of parent-based therapy for pediatric obesity (PBT) to a parent and child (FBT) program for childhood obesity. We assessed weight, diet, physical activity, and parenting, as well as cost-effectiveness, at baseline, post-treatment, and at 6- and 18-month follow-ups. Currently, all participants have been recruited and completed assessment visits, and the initial stages of data analysis are underway. Ultimately, by evaluating a PBT model, we hope to optimize available child obesity treatments and improve their translation into clinical settings. PMID- 26358538 TI - The complete mitochondrial genome of Protomelas annectens (Regan, 1922) (Perciformes: Cichlidae). AB - In this study, the complete mitogenome sequence of Protomelas annectens Regan 1922 has been sequenced by next-generation sequencing method. The assembled mitogenome consisting of 16 583 bp, includes 13 protein-coding genes, 22 transfer RNAs, 2 ribosomal RNAs genes and 1 control region. The overall base composition of P. annectens is 27.41% for A, 30.07% for C, 15.88% for G, 26.64% for T and shows 94% identity to threadfin cichlid, Petrochromis trewavasae. These data will provide useful molecular information for phylogenetic relationships within the family Cichlidae species. PMID- 26358539 TI - EGFR gene methylation is not involved in Royalactin controlled phenotypic polymorphism in honey bees. AB - The 2011 highly publicised Nature paper by Kamakura on honeybee phenotypic dimorphism, (also using Drosophila as an experimental surrogate), claims that a single protein in royal jelly, Royalactin, essentially acts as a master "on-off" switch in development via the epidermal growth factor receptor (AmEGFR), to seal the fate of queen or worker. One mechanism proposed in that study as important for the action of Royalactin is differential amegfr methylation in alternate organismal outcomes. According to the author differential methylation of amegfr was experimentally confirmed and shown in a supportive figure. Here we have conducted an extensive analysis of the honeybee egfr locus and show that this gene is never methylated. We discuss several lines of evidence casting serious doubts on the amegfr methylation result in the 2011 paper and consider possible origins of the author's statement. In a broader context, we discuss the implication of our findings for contrasting context-dependent regulation of EGFR in three insect species, Apis mellifera, D. melanogaster and the carpenter ant, Camponotus floridanus, and argue that more adequate methylation data scrutiny measures are needed to avoid unwarranted conclusions. PMID- 26358540 TI - Antibacterial effect of doxycycline-coated dental abutment surfaces. AB - Biofilm formation on dental abutment may lead to peri-implant mucositis and subsequent peri-implantitis. These cases are clinically treated with antibiotics such as doxycycline (Doxy). Here we used an electrochemical method of cathodic polarization to coat Doxy onto the outer surface of a dental abutment material. The Doxy-coated surface showed a burst release in phosphate-buffered saline during the first 24 h. However, a significant amount of Doxy remained on the surface for at least 2 weeks especially on a 5 mA-3 h sample with a higher Doxy amount, suggesting both an initial and a long-term bacteriostatic potential of the coated surface. Surface chemistry was analyzed by x-ray photoelectron spectroscopy and secondary ion mass spectrometry. Surface topography was evaluated by field emission scanning electron microscopy and blue-light profilometry. Longer polarization time from 1 h to 5 h and higher current density from 1 to 15 mA cm(-2) resulted in a higher amount of Doxy on the surface. The surface was covered by a layer of Doxy less than 100 nm without significant changes in surface topography. The antibacterial property of the Doxy-coated surface was analyzed by biofilm and planktonic growth assays using Staphylococcus epidermidis. Doxy-coated samples reduced both biofilm accumulation and planktonic growth in broth culture, and also inhibited bacterial growth on agar plates. The antibacterial effect was stronger for samples of 5 mA-3 h coated with a higher amount of Doxy compared to that of 1 mA-1 h. Accordingly, an abutment surface coated with Doxy has potential for preventing bacterial colonization when exposed to the oral cavity. Doxy-coating could be a viable way to control peri-implant mucositis and prevent its progression into peri-implantitis. PMID- 26358541 TI - Epigenetic Alterations Associated with War Trauma and Childhood Maltreatment. AB - Survivors of war trauma or childhood maltreatment are at increased risk for trauma-spectrum disorders such as post-traumatic stress disorder (PTSD). In addition, traumatic stress has been associated with alterations in the neuroendocrine and the immune system, enhancing the risk for physical diseases. Traumatic experiences might even affect psychological as well as biological parameters in the next generation, i.e. traumatic stress might have transgenerational effects. This article outlines how epigenetic processes, which represent a pivotal biological mechanism for dynamic adaptation to environmental challenges, might contribute to the explanation of the long-lasting and transgenerational effects of trauma. In particular, epigenetic alterations in genes regulating the hypothalamus-pituitary-adrenal axis as well as the immune system have been observed in survivors of childhood and adult trauma. These changes could result in enduring alterations of the stress response as well as the physical health risk. Furthermore, the effects of parental trauma could be transmitted to the next generation by parental distress and the pre- and postnatal environment, as well as by epigenetic marks transmitted via the germline. While epigenetic research has a high potential of advancing our understanding of the consequences of trauma, the findings have to be interpreted with caution, as epigenetics only represent one piece of a complex puzzle of interacting biological and environmental factors. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26358542 TI - A clinical and molecular review of inverted papilloma of the urinary tract: how to handle? AB - Inverted papilloma (IP) of the urinary tract is classified by the World Health Organisation as a non-invasive urothelial tumour with normal to minimal cytological atypia of the neoplastic cells. During the 1980s, it came under suspicion of having a premalignant or malignant potential and of being concurrent with urothelial cell carcinoma (UCC). This quandary has been proven difficult to solve, due to the fact that IP is very rare and literature mostly consists of case reports with varying levels of information, making strong meta-analyses problematic. New immunohistochemical techniques and genetic approaches are more frequently being used in the attempt to achieve better classifications, prognosis and treatment of lesions hereunder IP. This review will, in our awareness, be the first to combine the knowledge from retrospective studies with these new approaches for determining a possible premalignant potential and concurrency with UCC and subsequently outline a recommendation for follow-up. PMID- 26358543 TI - Erratum to: A Systematic Review of HIV and STI Behavior Change Interventions for Female Sex Workers in the United States. PMID- 26358544 TI - HIV Prevalence Among People Who Inject Drugs in Greater Kuala Lumpur Recruited Using Respondent-Driven Sampling. AB - The HIV epidemic in Malaysia is concentrated among people who inject drugs (PWID). Accurate estimates of HIV prevalence are critical for developing appropriate treatment and prevention interventions for PWID in Malaysia. In 2010, 461 PWID were recruited using respondent-driven sampling in Greater Kuala Lumpur, Malaysia. Participants completed rapid HIV testing and behavioral assessments. Estimates of HIV prevalence were computed for each of the three recruitment sites and the overall sample. HIV prevalence was 15.8 % (95 % CI 12.5-19.2 %) overall but varied widely by location: 37.0 % (28.6-45.4 %) in Kampung Baru, 10.3 % (5.0 15.6 %) in Kajang, and 6.3 % (3.0-9.5 %) in Shah Alam. Recruitment extended to locations far from initial interview sites but was concentrated around discrete geographic regions. We document the high prevalence of HIV among PWID in Greater Kuala Lumpur. Sustained support for community surveillance and HIV prevention interventions is needed to stem the HIV epidemic among PWID in Malaysia. PMID- 26358545 TI - Electronic effects on the substitution reactions of benzhydrols and fluorenyl alcohols. Determination of mechanism and effects of antiaromaticity. AB - A range of substituted benzhydrols and fluorenols were prepared and subjected to acid catalysed methanolysis. Analysis of the rates of each of these processes showed correlation with Hammett sigma(+) parameters as is consistent with the significant build-up of positive charge adjacent to the ring. In combination with the similarity of the electronic susceptibility of the processes, these data suggest that both reactions proceed through a unimolecular rate-determining step. This shows that the effect of fusion of the phenyl systems (and hence potentially introducing an antiaromatic carbocation intermediate) is only to slow the rate of reaction rather than change the mechanism of the process. PMID- 26358546 TI - Deagglomeration of multi-walled carbon nanotubes via an organic modifier: structure and mechanism. AB - We have investigated the agglomeration behaviour of two types of multi-walled carbon nanotubes (MWNTs; N-MWNTs and D-MWNTs), which have different chemical functionalities, average diameter, varying extent of agglomeration and agglomerations. The properties were altered by varying the agglomerated structure. The strength of the MWNT agglomerates was estimated via nanoindentation. The work done to indent D-MWNT agglomerates (3910.3 * 10(-8) erg) was higher than for N-MWNTs agglomerates (2316.4 * 10(-8) erg). An organic modifier, the Li salt of 6-aminohexanoic acid (Li-AHA), was used to deagglomerate the MWNTs in an aqueous medium. The stability of the aqueous dispersion of Li-AHA modified MWNTs was analyzed by UV-vis spectroscopy and zeta potential measurements. An increase in Li-AHA concentration increased the dispersion of MWNTs in the aqueous medium. Furthermore, the mechanism of dispersion of the two types of MWNTs in the aqueous medium in the presence of Li-AHA was determined based on the electrostatic charge repulsion between the negatively charged species. A fluorescence-activated cell sorting technique was used to assess the debundling of MWNT agglomerates in the aqueous medium. We examined the morphology property relationship in Li-AHA-modified MWNTs. PMID- 26358547 TI - Intravitreal steroid and anti-vascular endothelial growth agents for the management of retinal vein occlusion: evidence from randomized trials. AB - INTRODUCTION: Retinal vein occlusion (RVO) is a common retinal vascular disorder, affecting visual acuity and quality of life. Macular edema (ME) and retinal ischemia are the main causes for visual impairment in RVO. Although several modalities have been evaluated for the treatment of ME secondary to RVO in clinical trials, various questions need to be clarified when translating clinical trials into real-world practice. AREAS COVERED: Intravitreal steroids and anti VEGF agents are now widely used for the treatment of ME due to RVO. Herein, evidence from randomized controlled trials regarding the use of steroids and anti VEGF agents in ME related to RVO are presented. In addition, an approach regarding the optimal treatment regimen, the most suitable time for initiating treatment and monitoring patients, as well as the potential role of ischemia in the response to treatment and the impact of treatment on the natural course of the disease was made. EXPERT OPINION: A comprehensive presentation of randomized clinical trials evaluating intravitreal steroids and anti-VEGF treatment for RVO indicates that both are effective and safe. However, the comparative effectiveness of the various anti-VEGF agents, the most suitable dosing regimen and the effect of these agents on retinal ischemia remains unclear. PMID- 26358548 TI - High-density SNP assay development for genetic analysis in maritime pine (Pinus pinaster). AB - Maritime pine provides essential ecosystem services in the south-western Mediterranean basin, where it covers around 4 million ha. Its scattered distribution over a range of environmental conditions makes it an ideal forest tree species for studies of local adaptation and evolutionary responses to climatic change. Highly multiplexed single nucleotide polymorphism (SNP) genotyping arrays are increasingly used to study genetic variation in living organisms and for practical applications in plant and animal breeding and genetic resource conservation. We developed a 9k Illumina Infinium SNP array and genotyped maritime pine trees from (i) a three-generation inbred (F2) pedigree, (ii) the French breeding population and (iii) natural populations from Portugal and the French Atlantic coast. A large proportion of the exploitable SNPs (2052/8410, i.e. 24.4%) segregated in the mapping population and could be mapped, providing the densest ever gene-based linkage map for this species. Based on 5016 SNPs, natural and breeding populations from the French gene pool exhibited similar level of genetic diversity. Population genetics and structure analyses based on 3981 SNP markers common to the Portuguese and French gene pools revealed high levels of differentiation, leading to the identification of a set of highly differentiated SNPs that could be used for seed provenance certification. Finally, we discuss how the validated SNPs could facilitate the identification of ecologically and economically relevant genes in this species, improving our understanding of the demography and selective forces shaping its natural genetic diversity, and providing support for new breeding strategies. PMID- 26358549 TI - Primary prophylaxis of variceal bleeding in children and the role of MesoRex Bypass: Summary of the Baveno VI Pediatric Satellite Symposium. AB - Approaches to the management of portal hypertension and variceal hemorrhage in pediatrics remain controversial, in large part because they are not well informed by rigorous clinical studies. Fundamental biological and clinical differences preclude automatic application of approaches used for adults to children. On April 11-12, 2015, experts in the field convened at the first Baveno Pediatric Satellite Meeting to discuss and explore current available evidence regarding indications for MesoRex bypass (MRB) in extrahepatic portal vein obstruction and the role of primary prophylaxis of variceal hemorrhage in children. Consensus was reached regarding MRB. The vast majority of children with extrahepatic portal vein obstruction will experience complications that can be prevented by successful MRB surgery. Therefore, children with extrahepatic portal vein obstruction should be offered MRB for primary and secondary prophylaxis of variceal bleeding and other complications, if appropriate surgical expertise is available, if preoperative and intraoperative evaluation demonstrates favorable anatomy, and if appropriate multidisciplinary care is available for postoperative evaluation and management of shunt thrombosis or stenosis. In contrast, consensus was not achieved regarding primary prophylaxis of varices. Although variceal hemorrhage is a concerning complication of portal hypertension in children, the first bleed appears to be only rarely fatal and the associated morbidity has not been well characterized. CONCLUSION: There are few pediatric data to indicate the efficacy and safety of pharmacologic or endoscopic therapies as primary prophylaxis or that prevention of a sentinel variceal bleed will ultimately improve survival; therefore, no recommendation for primary prophylaxis with endoscopic variceal ligation, sclerotherapy, or nonspecific beta-blockade in children was proposed. PMID- 26358550 TI - Synthesis, characterization, release kinetics and toxicity profile of drug-loaded starch nanoparticles. AB - The current research work focuses on the medical application of the cost effective cross-linked starch nanoparticles, for the transdermal delivery using Diclofenac sodium (DS) as a model drug. The prepared DS-cross-linked starch nanoparticles were synthesized using nanoprecipitation technique at different concentrations of sodium tripolyphosphate (STPP) in the presence of Tween 80 as a surfactant. The resultant cross-linked starch nanoparticles loaded with DS were characterized using world-class facilities such as TEM, DLS, FT-IR, XRD, and DSc. The efficiency of DS loading was also evaluated via entrapment efficiency as well as in vitro release and histopathological study on rat skin. The optimum nanoparticles formulation selected by the JMP((r)) software was the formula that composed of 5% maize starch, 57.7mg DS and 0.5% STPP and 0.4% Tween 80, with particle diameter of about 21.04nm, polydispersity index of 0.2 and zeta potential of -35.3mV. It is also worth noting that this selected formula shows an average entrapment efficiency of 95.01 and sustained DS release up to 6h. The histophathological studies using the best formula on rat skin advocate the use of designed transdermal DS loaded cross-linked starch nanoparticles as it is safe and non-irritant to rat skin. The overall results indicate that, the starch nanoparticles could be considered as a good carrier for DS drug regarding the enhancement in its controlled release and successful permeation, thus, offering a promising nanoparticulate system for the transdermal delivery non-steroidal anti inflammatory drug (NSAID). PMID- 26358551 TI - Sodium dodecyl sulphate (SDS) induced changes in propensity and kinetics of alpha lactalbumin fibrillation. AB - Understanding surfactants induced changes on protein folding, aggregation, and fibrillation has a lot of implications in their laboratory and industrial applications. The effect of an anionic surfactant, sodium dodecyl sulphate (SDS), on fibrillation of an acidic protein alpha-lactalbumin (alpha-LA) at neutral pH condition was investigated. SDS at lower concentrations increased the lag time by nearly two-fold whereas the fibril elongation rate was not significantly altered. At the concentrations above 0.2mM, SDS lengthened the lag time by many-fold (~60), but fibril elongation was accelerated by 3-6 fold. At the concentrations above 2mM, SDS inhibited alpha-LA fibrillation and led it to the formation of amorphous aggregates. These results were compared with the effect of SDS on the fibrillation of lysozyme, a basic protein. Though fibril inhibition was observed on both the proteins at the micellar concentrations of SDS, there were differences in the effect on lag time and elongation rate at the lower concentrations of SDS. This suggests that the inhibition of protein fibrillation by SDS-micelles might be a common mechanism irrespective of the surface charges on protein. PMID- 26358552 TI - Effect of layer-by-layer polyelectrolyte method on encapsulation of vanillin. AB - The objective of this work was to microencapsulate vanillin by multilayer emulsion followed by spray drying, aiming to protect it and control its release. An electrostatic layer-by-layer deposition method was used to create the multilayered interfacial membranes around microcapsules with different compositions: (i) one-layer (soy protein isolate); (ii) two-layer (soy protein isolate - OSA starch); (iii) three-layer (soy protein isolate - OSA starch - Chitosan). The morphology of the microcapsules was analyzed by scanning electronic microscopy. The hygroscopicity, solubility, particle size, encapsulation efficiency, Fourier transform infrared spectroscopy and release into water (37 degrees C and 80 degrees C) were also examined. FTIR confirmed the interaction between the wall materials. All microcapsules were not very water soluble or hygroscopic while three-layer microcapsules compared to one and two layer microcapsules have lower moisture content and predominantly shriveled surfaces. The results indicated it was possible to encapsulate vanillin with the techniques employed and that these protected the vanillin even at 80 degrees C. The reduced solubility and low release rates indicated the enormous potential of the vehicle developed in controlling the release of the vanillin into the food and pharmaceuticals. PMID- 26358553 TI - Preparation of cobalt nanoparticles from polymorphic bacterial templates: A novel platform for biocatalysis. AB - Nanoparticles have gathered significant research attention as materials for enzyme immobilization due to their advantageous properties such as low diffusion rates, ease of manipulation, and large surface areas. Here, polymorphic cobalt nanoparticles of varied sizes and shapes were prepared using Micrococcus lylae, Bacillus subtilis, Escherichia coli, Paracoccus sp., and Haloarcula vallismortis as bacterial templates. Furthermore, nine lipases/carboxylesterases were successfully immobilized on these cobalt nanoparticles. Especially, immobilized forms of Est-Y29, LmH, and Sm23 were characterized in more detail for potential industrial applications. Immobilization of enzymes onto cobalt oxide nanoparticles prepared from polymorphic bacterial templates may have potential for efficient hydrolysis on an industrial-scale, with several advantages such as high retention of enzymatic activity, increased stability, and strong reusability. PMID- 26358554 TI - Biocatalytic role of potato starch synthase III for alpha-glucan biosynthesis in Synechocystis sp. PCC6803 mutants. AB - A potato starch synthase III (PSSIII) was expressed in the Synechocystis mutants deficient in either glycogen synthase I (M1) or II (M2) to replenish alpha-(1,4) linkage synthesizing activity, resulting in new mutants, PM1 and PM2, respectively. These mutants were applied to study the role of exogenous plant starch synthase for starch/glycogen biosynthesis mechanism established in the cyanobacteria. The remaining glycogen synthase genes in PM1 and PM2 were further disrupted to make the mutants PM12 and PM21 which contained PSSIII as the sole glycogen/starch synthase. Among wild type and mutants, there were no significant differences in the amount of alpha-glucan produced. All the mutants harboring active PSSIII produced alpha-glucans with relatively much shorter and less longer alpha-1,4 chains than wild-type glycogen, which was exactly in accordance with the increase in glycogen branching enzyme activity. In fact, alpha-glucan structure of PM1 was very similar to those of PM12 and PM21, and PM2 had more intermediate chains than M2. This result suggests PSSIII may have distributive elongation property during alpha-glucan synthesis. In conclusion, the Synechocystis as an expression model system of plant enzymes can be applied to determine the role of starch synthesizing enzymes and their association during alpha-glucan synthesis. PMID- 26358555 TI - Histopathological and combinatorial effects of the metalloprotease InhA1 and Cry proteins of Bacillus thuringiensis against Spodoptera littoralis. AB - The zinc metalloprotease (InhA) of Bacillus thuringiensis specifically hydrolyzes cecropins and attacins, two antibacterial peptides in the immune hemolymph of insects, leading to a high resistance of the bacteria to the humoral defense system of its host. In the present study, the inhA gene of B. thuringiensis strain BUPM28 was cloned and the nucleotide sequence analysis revealed that it was identical to that of B. thuringiensis 8010. The expressed InhA1 protein in Escherichia coli showed toxicity to neonate Spodoptera littoralis larvae with a LC50 of 2.07+/-0.72MUg/cm(2). Study of the effect of combining Cry proteins with InhA1 showed that one improves the toxicity of the other one against S. littoralis. Investigation of the histopathological effect of this metalloprotease showed an extensive damage of S. littoralis epithelium tissue. These results provide an insight to the use of InhA as supplement to Cry toxins to improve the efficacy of B. thuringiensis formulations and to overcome possible resistance problems. PMID- 26358556 TI - Magnetoresistance in the Spin-Orbit Kondo State of Elemental Bismuth. AB - Materials with strong spin-orbit coupling, which competes with other particle particle interactions and external perturbations, offer a promising route to explore novel phases of quantum matter. Using LDA + DMFT we reveal the complex interplay between local, multi-orbital Coulomb and spin-orbit interaction in elemental bismuth. Our theory quantifies the role played by collective dynamical fluctuations in the spin-orbit Kondo state. The correlated electronic structure we derive is promising in the sense that it leads to results that might explain why moderate magnetic fields can generate Dirac valleys and directional-selective magnetoresistance responses within spin-orbit Kondo metals. PMID- 26358557 TI - Updating stored memory requires adult hippocampal neurogenesis. AB - Adult hippocampal neurogenesis appears to influence hippocampal functions, such as memory formation for example. While adult hippocampal neurogenesis is known to be involved in hippocampal-dependent learning and consolidation processes, the role of such immature neurons in memory reconsolidation, a process involved in the modification of stored memories, remains unclear. Here, using a novel fast X ray ablation protocol to deplete neurogenic cells, we have found that adult hippocampal neurogenesis is required to update object recognition stored memory more than to reinforce it. Indeed, we show that immature neurons were selectively recruited to hippocampal circuits during the updating of stored information. Thus, our data demonstrate a new role for neurogenesis in cognitive processes, adult hippocampal neurogenesis being required for the updating of stored OR memories. These findings suggest that manipulating adult neurogenesis may have a therapeutic application in conditions associated with traumatic stored memory, for example. PMID- 26358558 TI - Phosphorylation of CONSTANS and its COP1-dependent degradation during photoperiodic flowering of Arabidopsis. AB - Seasonal flowering involves responses to changes in day length. In Arabidopsis thaliana, the CONSTANS (CO) transcription factor promotes flowering in the long days of spring and summer. Late flowering in short days is due to instability of CO, which is efficiently ubiquitinated in the dark by the CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1) E3 ligase complex. Here we show that CO is also phosphorylated. Phosphorylated and unphosphorylated forms are detected throughout the diurnal cycle but their ratio varies, with the relative abundance of the phosphorylated form being higher in the light and lower in the dark. These changes in relative abundance require COP1, because in the cop1 mutant the phosphorylated form is always more abundant. Inactivation of the PHYTOCHROME A (PHYA), CRYPTOCHROME 1 (CRY1) and CRYPTOCHROME 2 (CRY2) photoreceptors in the phyA cry1 cry2 triple mutant most strongly reduces the amount of the phosphorylated form so that unphosphorylated CO is more abundant. This effect is caused by increased COP1 activity, as it is overcome by introduction of the cop1 mutation in the cop1 phyA cry1 cry2 quadruple mutant. Degradation of CO is also triggered in red light, and as in darkness this increases the relative abundance of unphosphorylated CO. Finally, a fusion protein containing truncated CO protein including only the carboxy-terminal region was phosphorylated in transgenic plants, locating at least one site of phosphorylation in this region. We propose that CO phosphorylation contributes to the photoperiodic flowering response by enhancing the rate of CO turnover via activity of the COP1 ubiquitin ligase. PMID- 26358559 TI - Tentative clinical diagnosis of Lujan-Fryns syndrome--A conglomeration of different genetic entities? AB - The clinical diagnosis of Lujan-Fryns syndrome (LFS) comprises X-linked intellectual disability (XLID) with marfanoid habitus, distinct combination of minor facial anomalies and nasal speech. However the definition of syndrome was significantly broadened since the original report and implies ID with marfanoid habitus. Mutations of three genes (MED12, UPF3B, and ZDHHC9) have been reported in "broadly defined" LFS. We examined these genes in 28 individuals with a tentative clinical diagnosis of LFS but we did not identify any causative mutation. By molecular karyotyping we detected other disorders, i.e., Phelan McDermid syndrome and 16p11.2 microduplication, each in one patient. One affected individual was carrier of a different recurrent duplication on 16p11.2 that has been reported several times to the DECIPHER and ISCA databases in individuals with autism, intellectual disability (ID), and developmental delay. It may represent a new duplication syndrome. We also identified previously unreported de novo duplication on chromosome 12p13.31 which we considered to be disease causing. X-exome sequencing of four individuals revealed private or non-recurrent mutations in NKAP and LAS1L in one patient each. While LFS is defined as a form of XLID, there seem to be various conditions that have rather similar phenotypes. Therefore, the combination of ID and marfanoid habitus in a male patient is not sufficient for the diagnosis of LFS. We suggest that the diagnosis of LFS in patients with ID and marfanoid habitus should be made only in presence of specific facial features, nasal speech and obvious X-linked segregation of the disorder or an unambiguously pathogenic mutation in the MED12. PMID- 26358561 TI - Negative chromatography purification of hepatitis B virus-like particles using poly(oligo(ethylene glycol) methacrylate) grafted cationic adsorbent. AB - Poly(oligo(ethylene glycol) methacrylate) (POEGMA), an inert polymer was grafted onto an anion exchange adsorbent for the exclusion of relatively larger hepatitis B virus-like particles (HB-VLPs) from the anion exchange ligand (Q) and at the same time this process allowed the selective adsorption of smaller size Escherichia coli host cell proteins (HCPs). The chain lengths of the POEGMA grafted were modulated by varying the amount of monomers used in the polymer grafting. The purification factor and yield of the HB-VLPs obtained from the flow through of negative chromatography were 2.3 and 66.0+/-3.1%, respectively, when shorter chain length of POEGMA (SQ) was grafted. Adsorbent grafted with longer chain of POEGMA (LQ) excluded some HCPs that are larger in size together with the HB-VLPs, reducing the purity of the recovered HB-VLPs. Further heat-treatment of the flow-through pool from SQ followed by centrifugation increased the purity of heat stable HB-VLPs to 87.5+/-1.1%. Heat-treatment of the flow through sample resulted in thermal denaturation and aggregation of HCPs, while the heat stable HB-VLPs still remained intact as observed under a transmission electron microscope. The performance of the negative chromatography together with heat treatment in the purification of HB-VLPs is far better than the reported bind-and elute techniques. PMID- 26358560 TI - Respiration and substrate transport rates as well as reactive oxygen species production distinguish mitochondria from brain and liver. AB - BACKGROUND: Aberrant mitochondrial function, including excessive reactive oxygen species (ROS) production, has been implicated in the pathogenesis of human diseases. The use of mitochondrial inhibitors to ascertain the sites in the electron transport chain (ETC) resulting in altered ROS production can be an important tool. However, the response of mouse mitochondria to ETC inhibitors has not been thoroughly assessed. Here we set out to characterize the differences in phenotypic response to ETC inhibitors between the more energetically demanding brain mitochondria and less energetically demanding liver mitochondria in commonly utilized C57BL/6J mice. RESULTS: We show that in contrast to brain mitochondria, inhibiting distally within complex I or within complex III does not increase liver mitochondrial ROS production supported by complex I substrates, and liver mitochondrial ROS production supported by complex II substrates occurred primarily independent of membrane potential. Complex I, II, and III enzymatic activities and membrane potential were equivalent between liver and brain and responded to ETC. inhibitors similarly. Brain mitochondria exhibited an approximately two-fold increase in complex I and II supported respiration compared with liver mitochondria while exhibiting similar responses to inhibitors. Elevated NADH transport and heightened complex II-III coupled activity accounted for increased complex I and II supported respiration, respectively in brain mitochondria. CONCLUSIONS: We conclude that important mechanistic differences exist between mouse liver and brain mitochondria and that mouse mitochondria exhibit phenotypic differences compared with mitochondria from other species. PMID- 26358562 TI - Comparison of electron and chemical ionization modes for the quantification of thiols and oxidative compounds in white wines by gas chromatography-tandem mass spectrometry. AB - A rapid, sensitive method for assaying volatile impact compounds in white wine was developed using gas chromatography-tandem mass spectrometry (GC-MS/MS) technology, with a triple quadrupole analyzer operating in chemical ionization and electron impact mode. This GC-MS/MS method made it possible to assay volatile thiols (3SH: 3-sulfanylhexanol, formerly 3MH; 3SHA: 3-sulfanylhexyl acetate, formerly 3MHA; 4MSP: 4-methyl-4-sulfanylpentan-2-one, formerly 4MMP; BM: benzenemethanethiol; E2SA: ethyl 2-sulfanylacetate; and 2FM: 2-furanmethanethiol) and odoriferous oxidation markers (Sotolon: 4,5-dimethyl-3-hydroxy-2(5)H furanone, methional, and phenylacetaldehyde) simultaneously in dry white wines, comparing electron impact (EI) and chemical ionization (CI) modes. More molecular ions were produced by CI than protonated molecules, despite the greater fragmentation caused by EI. So, even using the best reactant gas giving the highest signal for thiols, EI was the best ionization mode, with the lowest detection limits. For all compounds of interest, the limits of quantification (LOQ) obtained were well below their detection thresholds (ranging from 0.5 to 8.5ng/L for volatile thiols and 65-260ng/L for oxidation markers). Recovery rates ranged from 86% to 111%, reproducibility (in terms of relative standard deviation; RSD) was below 18% in all cases, with correlation coefficients above 0.991 for all analytes. The method was successfully applied to the analysis of compounds of interest in Sauvignon Blanc wines from a single estate and ten different vintages. PMID- 26358563 TI - Separation of calcium-48 isotope by crown ether chromatography using ethanol/hydrochloric acid mixed solvent. AB - Benzo-18-crown-6 ether resin embedded in porous silica beads was synthesized and used as the packing material for chromatographic separation of (48)Ca isotope. The aim of the present work is to develop efficient isotope enrichment process for double beta decay nuclide (48)Ca. To this end, ethanol/HCl mixed solvent was selected as the medium for the chromatographic separation. Adsorption of calcium on the resin was studied at different HCl concentrations and different ethanol mixing ratios in batch-wise experiments. A very interesting phenomenon was observed; Ca adsorption is controlled not by the overall HCl concentration of the mixed solvent, but by the initial concentration of added HCl solution. Calcium break-through chromatography experiments were conducted by using 75v/v% ethanol/25v/v% 8M HCl mixed solvent at different flow rates. The isotope separation coefficient between (48)Ca and (40)Ca was determined as 3.8*10(-3), which is larger than that of pure HCl solution system. Discussion is extended to the chromatographic HETP, height equivalent to a theoretical plate. PMID- 26358564 TI - [A sebaceous cyst infection by Actinomyces europaeus]. PMID- 26358565 TI - Acupuncture and postpartum pyogenic sacroiliitis: a case report. AB - INTRODUCTION: Pyogenic sacroiliitis, a rare form of septic arthritis, occurs in patients following trauma, intravenous drug use, genitourinary infections and pregnancy. Here we report a rare case where both acupuncture and pregnancy served as predisposing risk factors to the development of this infection. CASE PRESENTATION: A 33-year-old white woman received several sessions of acupuncture treatment during her gestation at the site of her sacroiliac joint for sciatica; she developed biopsy-confirmed sacroiliitis with methicillin-sensitive Staphylococcus aureus during the immediate postpartum period. The diagnosis, medical management and treatment course are described. CONCLUSIONS: Low back and pelvic pain are common conditions during pregnancy and postpartum. Acupuncture is a common modality of medication-free treatment used by many patients. Recognition of the potential complications of such therapies can lead to early diagnosis, accurate treatment, decreased morbidity and increased chances for a successful outcome. PMID- 26358566 TI - Therapeutic exercise for prevention, treatment and rehabilitation of musculoskeletal pain and function. PMID- 26358567 TI - Investigation of Pseudomonas aeruginosa quorum-sensing signaling system for identifying multiple inhibitors using molecular docking and structural analysis methodology. AB - Pseudomonas aeruginosa is an opportunistic human pathogen and a common Gram negative bacterium in hospital-acquired infections. It causes death in many burn victims, cystic-fibrosis and neutropenic-cancer patients. It is known that P. aeruginosa biofilm maturation and production of cell-associated and extracellular virulence factors such as pyocyanin, elastase and rhamnolipids are under the control of a quorum-sensing (QS) system. Among several proteins involved in the Pseudomonas QS mechanism, LasR and PqsE play an important role in its cascade signaling system. They can cause increases in QS factors, biofilm maturation, and the production of virulence factors. Therefore, inhibition of these proteins can reduce the pathogenicity of P. aeruginosa. According to the structure of corresponding auto-inducers bound to these proteins, in silico calculations were performed with some non-steroidal anti-inflammatory drugs (NSAIDs) to estimate possible interactions and find the co-inhibitors of LasR and PqsE. The results showed that oxicams (Piroxicam and Meloxicam) can interact well with active sites of both proteins with the Ki of 119.43 nM and 4.0 MUM for Meloxicam and 201.39 nM and 4.88 MUM against LasR and PqsE, respectively. These findings suggested that Piroxicam and Meloxicam can be used as potential inhibitors for control of the P. aeruginosa QS signaling system and biofilm formation, and may be used in the design of multiple inhibitors. PMID- 26358568 TI - Percutaneous management of pulmonary metastases arising from colorectal cancer; a systematic review. AB - BACKGROUND: Radiofrequency ablation (RFA) is a well-established treatment modality for colorectal hepatic metastases, the success of which has prompted its use to treat other lesions such as colorectal pulmonary metastases (CRPM). Our aim was to perform a systematic review of the evidence and to assess the safety and effectiveness of ablative techniques in the management of CRPM. METHOD: A literature search was performed using PubMed, Embase, Cochrane Library, CINAHL and Google scholar databases to identify studies, which analysed ablative techniques and their effectiveness in the management of CRPM. The primary outcome measures were overall survival, local recurrence rates and disease free survival. Secondary outcome measures were complication (major/minor), chest drain insertion rates and follow up duration. RESULTS: Eight studies were included in the review with a total of 903 patients and all of which used RFA for ablation. Mortality from ablation was <1% with overall survival ranging from 31 to 67 months. 1, 3 and 5 year survival ranges of 84-95%, 35-72% and 20-54% respectively. Local progression following ablation ranged from 9 to 21%. Major complication rates were noted in 0.5%-8% of patients with minor complications ranging between 7% and 33%. 23% of patients required chest drain insertion post procedure. CONCLUSION: s: RFA is a safe and effective technique for the management of CRPM. However, in the absence of large randomised controlled trials it is unclear where RFA should sit in the treatment algorithm for patients with CRPM. PMID- 26358571 TI - Continuing Excellence at the Heart of Cardiology: European Society of Cardiology publishing in 2015. PMID- 26358569 TI - Exercise intervention in people with cancer undergoing adjuvant cancer treatment following surgery: A systematic review. AB - BACKGROUND: Remaining physically active during and after cancer treatment is known to improve associated adverse effects, improve overall survival and reduce the probability of relapse. This systematic review addresses the question: is an exercise training programme beneficial in people with cancer undergoing adjuvant cancer treatment following surgery. METHODS: A systematic database search of Embase, Ovid, Medline without Revisions, SPORTDiscus, Web of Science, Cochrane Library and ClinicalTrials.gov for any randomised controlled trials (RCT) or non RCT addressing the effect of an exercise training programme in those having adjuvant cancer treatment following surgery was conducted. RESULTS: The database search yielded 6489 candidate abstracts of which 94 references included the required terms. A total of 17 articles were included in this review. Exercise training is safe and feasible in the adjuvant setting and furthermore may improve measures of physical fitness and health related quality of life (HRQoL). CONCLUSION: This is the first systematic review on exercise training interventions in people with cancer undergoing adjuvant cancer treatment following surgery. Due to the lack of adequately powered RCTs in this area, it remains unclear whether exercise training in this context improves clinical outcomes other physical fitness and HRQoL. It remains unclear what is the optimal timing of initiation of an exercise programme and what are the best combinations of elements within an exercise training programme to optimise training efficacy. Furthermore, it is unclear if initiating such exercise programmes at cancer diagnosis may have a long-lasting effect on physically activity throughout the subsequent life course. PMID- 26358570 TI - Tricuspid regurgitation diagnosis and treatment. AB - Tricuspid regurgitation (TR) is the most common lesion of the tricuspid valve (TV). Mild TR is common and usually is benign. However, moderate or severe TR can lead to irreversible myocardial damage and adverse outcomes. Despite these findings, few patients with significant TR undergo surgery. The treatment of functional (secondary) TR in particular remains controversial because of high rates of residual or recurrent TR and poor outcomes following surgical intervention. Traditional teaching that functional TR resolves on its own if the underlying disease is successfully treated has proven to be incorrect. This review aims to clarify management of TR by describing the anatomy, pathophysiology, diagnosis, and treatment of TR, including the eventual possibility of percutaneous TV therapy. PMID- 26358572 TI - Leaflet migration in an aortic bileaflet mechanical prosthesis. PMID- 26358573 TI - Pseudoaneurysm following transradial coronary angiogram. PMID- 26358574 TI - The CHA2DS2-VASc score for stroke risk stratification in patients with atrial fibrillation: a brief history. PMID- 26358575 TI - Current status of cell therapy for non-ischaemic cardiomyopathy: a brief overview. PMID- 26358576 TI - A rare case of ascending aortic stenosis. PMID- 26358577 TI - Growth, biofilm formation, antifungal susceptibility and oxidative stress resistance of Candida glabrata are affected by different glucose concentrations. AB - Glucose is an important fuel source to support many living organisms. Its importance in the physiological fitness and pathogenicity of Candida glabrata, an emerging human fungal pathogen has not been extensively studied. The present study aimed to investigate the effects of glucose on the growth, biofilm formation, antifungal susceptibility and oxidative stress resistance of C. glabrata. In addition, its effect on the expression of a putative high affinity glucose sensor gene, SNF3 was also investigated. Glucose concentrations were found to exert effects on the physiological responses of C. glabrata. The growth rate of the species correlated positively to the amount of glucose. In addition, low glucose environments were found to induce C. glabrata to form biofilm and resist amphotericin B. Conversely, high glucose environments promoted oxidative stress resistance of C. glabrata. The expression of CgSNF3 was found to be significantly up-regulated in low glucose environments. The expression of SNF3 gene in clinical isolates was found to be higher compared to ATCC laboratory strains in low glucose concentrations, which may explain the better survivability of clinical isolates in the low glucose environment. These observations demonstrated the impact of glucose in directing the physiology and virulence fitness of C. glabrata through the possible modulation by SNF3 as a glucose sensor, which in turn aids the species to adapt, survive and thrive in hostile host environment. PMID- 26358578 TI - Sarcopenia and failure to rescue following liver transplantation. AB - INTRODUCTION: Sarcopenic liver transplant recipients have higher rates of mortality, but mechanisms underlying these rates remain unclear. Failure to rescue (FTR) has been shown to be a primary driver of mortality following major general and vascular surgery. We hypothesized that FTR is common in sarcopenic liver transplant recipients. METHODS: We retrospectively reviewed 348 liver transplant recipients with perioperative CT scans. Analytic morphomic techniques were used to assess trunk muscle size via total psoas area (TPA). One-yr major complication and FTR rates were calculated across TPA tertiles. RESULTS: The one yr complication rate was 77% and the FTR rate was 19%. Multivariate regression showed TPA as a significant predictor of FTR (OR = 0.27 per 1000 mm(2) increase in TPA, p < 0.001). Compared to patients in the largest muscle tertile, patients in the smallest tertile had 1.4-fold higher adjusted complication rates (91% vs. 66%) and 2.8-fold higher adjusted FTR rates (22% vs. 8%). DISCUSSION: These results suggest that mortality in sarcopenic liver transplant recipients may be strongly related to FTR. Efforts aimed at early recognition and management of complications may decrease postoperative mortality. Additionally, this work highlights the need for expanded multicenter collaborations aimed at collection and analysis of postoperative complications in liver transplant recipients. PMID- 26358579 TI - Complete mitochondrial genome of Drosophila albomicans. AB - Drosophila albomicans has been widely used as an important animal model for chromosome evolution. In this study, the mitochondrial genome sequence of this species is determined and described for the first time. The mitochondrial genome (15 849 bp) encompasses two rRNA, 22 tRNA, and 13 protein-coding genes. Genome content and structure are similar to those reported from other Drosophila mitochondrial genomes. Phylogeny analysis indicates that D. albomicans have a closer genetic relationship with Drosophil aincompta and Drosophil alittoralis. This mitochondrial genome is potentially important for studying molecular evolution and conservation genetics in Drosophila genus. PMID- 26358580 TI - Particle dynamics and deposition in true-scale pulmonary acinar models. AB - Particle transport phenomena in the deep alveolated airways of the lungs (i.e. pulmonary acinus) govern deposition outcomes following inhalation of hazardous or pharmaceutical aerosols. Yet, there is still a dearth of experimental tools for resolving acinar particle dynamics and validating numerical simulations. Here, we present a true-scale experimental model of acinar structures consisting of bifurcating alveolated ducts that capture breathing-like wall motion and ensuing respiratory acinar flows. We study experimentally captured trajectories of inhaled polydispersed smoke particles (0.2 to 1 MUm in diameter), demonstrating how intrinsic particle motion, i.e. gravity and diffusion, is crucial in determining dispersion and deposition of aerosols through a streamline crossing mechanism, a phenomenon paramount during flow reversal and locally within alveolar cavities. A simple conceptual framework is constructed for predicting the fate of inhaled particles near an alveolus by identifying capture and escape zones and considering how streamline crossing may shift particles between them. In addition, we examine the effect of particle size on detailed deposition patterns of monodispersed microspheres between 0.1-2 MUm. Our experiments underline local modifications in the deposition patterns due to gravity for particles >=0.5 MUm compared to smaller particles, and show good agreement with corresponding numerical simulations. PMID- 26358581 TI - Erratum to: Physical activity attenuates the mid-adolescent peak in insulin resistance but by late adolescence the effect is lost: a longitudinal study with annual measures from 9-16 years (EarlyBird 66). PMID- 26358582 TI - Pre-pregnancy dietary patterns and risk of gestational diabetes mellitus: results from an Australian population-based prospective cohort study. AB - AIMS/HYPOTHESIS: We examined the associations between pre-pregnancy dietary patterns and the incidence of gestational diabetes mellitus (GDM) in a population based cohort study of women of reproductive age. METHODS: The Australian Longitudinal Study on Women's Health included 3,853 women without pre-existing diabetes who were followed-up between 2003 and 2012. Pre-pregnancy dietary patterns were derived using factor analysis based on 101 food items from a validated food frequency questionnaire. GDM was self-reported and validated in a subsample. Multivariable regression models with generalised estimating equations were used to estimate RR and 95% CI. RESULTS: During 9 years follow-up, 292 GDM cases (4.4%) were documented in 6,626 pregnancies. No associations were found for the 'Fruit and low-fat dairy' and 'Cooked vegetables' patterns. The 'Meats, snacks and sweets' pattern was associated with higher GDM risk after adjustment for socioeconomic, reproductive and lifestyle factors (RR [95% CI] per SD increase in score: 1.38 [1.02, 1.86]). Further adjustment for BMI attenuated the results (1.35 [0.98, 1.81]). In stratified analysis, the 'Meats, snacks and sweets' pattern was associated with significantly higher GDM risk in parous and obese women, and in women with lower educational qualifications. The 'Mediterranean-style' pattern was associated with lower GDM risk in the fully adjusted model (0.85 [0.76, 0.98]). CONCLUSIONS/INTERPRETATION: These findings support general dietary recommendations for women of reproductive age to consume a diet rich in vegetables, whole grains, nuts and fish, and low in red and processed meats and snacks. Further prospective studies are needed to confirm these findings. PMID- 26358583 TI - Sensory neuropathy hampers nociception-mediated bone marrow stem cell release in mice and patients with diabetes. AB - AIMS/HYPOTHESIS: Upon tissue injury, peripheral sensory neurons release nociceptive factors (e.g. substance P [SP]), which exert local and systemic actions including the recruitment of bone marrow (BM)-derived haematopoietic stem and progenitor cells (HSPCs) endowed with paracrine pro-angiogenic properties. We herein explore whether diabetic neuropathy interferes with these phenomena. METHODS: We first investigated the presence of sensory neuropathy in the BM of patients with type 2 diabetes by immunohistochemistry and morphometry analyses of nerve size and density and assessment of SP release by ELISA. We next analysed the association of sensory neuropathy with altered HSPC release under ischaemia or following direct stimulation with granulocyte colony-stimulating factor (G CSF). BM and circulating HSPCs expressing the neurokinin 1 receptor (NK1R), which is the main SP receptor, were measured by flow cytometry. We finally assessed whether an altered modulation of SP secretion interferes with the mobilisation and homing of NK1R-HSPCs in a mouse model of type 2 diabetes after limb ischaemia (LI). RESULTS: Nociceptive fibres were reduced in the BM of patients and mice with type 2 diabetes. Patients with neuropathy showed a remarkable reduction in NK1R-HSPC mobilisation under ischaemia or upon G-CSF stimulation. Following LI, diabetic mice manifested an altered SP gradient between BM, peripheral blood and limb muscles, accompanied by a depressed recruitment of NK1R-HSPCs to the ischaemic site. CONCLUSIONS/INTERPRETATION: Sensory neuropathy translates into defective liberation and homing of reparative HSPCs. Nociceptors may represent a new target for treatment of diabetic complications. PMID- 26358584 TI - The influence of type 1 diabetes on pancreatic weight. AB - AIMS/HYPOTHESIS: Previous studies of pancreases obtained at autopsy or by radiography note reduced pancreas weight (PW) and size, respectively, in type 1 diabetes; this finding is widely considered to be the result of chronic insulinopenia. This literature is, however, limited with respect to the influence of age, sex, anthropometric factors and disease duration on these observations. Moreover, data are sparse for young children, a group of particular interest for type 1 diabetes. We hypothesised that the pancreas-to-body weight ratio would normalise confounding inter-subject factors, thereby permitting better characterisation of PW in type 1 diabetes. METHODS: Transplant-grade pancreases were recovered from 216 organ donors with type 1 diabetes (n = 90), type 2 diabetes (n = 40) and no diabetes (n = 86). Whole-organ and head, body and tail weights were determined. The relative PW (RPW; PW [g] / body weight [kg]) was calculated and tested for normalisation of potential differences due to age, sex and BMI. RESULTS: PW significantly correlated with body weight in control donors (R (2) = 0.76, p < 0.001) while RPW (1.03 +/- 0.36, mean +/- SD) did not significantly differ across ages (0-58 years). Donors with type 1 diabetes (0.57 +/- 0.18, p < 0.001), but not those with type 2 diabetes (0.93 +/- 0.30), had significantly lower RPW. The relative weights of each pancreatic region from donors with type 1 diabetes were significantly smaller than those of regions from control donors and donors with type 2 diabetes (p < 0.001). Perhaps most interestingly, the RPW was not significantly associated with duration of type 1 diabetes or type 2 diabetes. CONCLUSIONS/INTERPRETATION: RPW allows for comparisons across a wide range of donor ages by eliminating confounding variables. These data validate an interesting feature of the type 1 diabetes pancreas and underscore the need for additional studies to identify the mechanistic basis for this finding, including those beyond the chronic loss of endogenous insulin secretion. PMID- 26358585 TI - The effects of injectable calcium silicate-based composites with the Chinese herb on an osteogenic accelerator in vitro. AB - We aimed to investigate the physicochemical and biological effects of calcium silicate (CS)-based cements together with the Chinese medicine Xu Duan (XD) after seeding with human adipose-derived stem cells (hADSCs). Here, we fabricated CS based substrates with different ratios of XD (0%, 5% and 10%) as bioactive and biodegradable biocomposites, subsequent to examining their respective effectiveness for bone repair. The setting time, the injectability, the mechanical properties measured by diametral tensile strength (DTS), the in vitro degradation determined by changes in the weight loss of the composites, the characteristic formation of bone-like apatite, and cell growth as well as osteogenesis protein and bone mineralization were comprehensively evaluated before and after immersion in simulated body fluid (SBF), respectively. At the end of testing, with regard to physicochemical effects, the CS-based substrate mixed with the 10% XD group showed significantly sound mechanical properties, an applicable setting time and injectability and the formation of a dense bone-like apatite layer. In terms of biological effects, the CS-based substrate with the 10% XD group showed a significant development of osteogenic activities with sound cell proliferation and higher alkaline phosphatase (ALP) activity, as well as indicating osteogenic differentiation, greater osteocalcin (OC) protein secretion and clearly calcified tissue mineralization. The present drug-release strategy with CS-based cements may pave the way for future alternative bone repair therapy. PMID- 26358586 TI - Consensus Sequence of 27 African Horse Sickness Virus Genomes from Viruses Collected over a 76-Year Period (1933 to 2009). AB - We announce the complete consensus genome sequence of 27 African horse sickness viruses, representing all nine African horse sickness virus (AHSV) serotypes from historical and recent isolates collected over a 76-year period (1933 to 2009). The data set includes the sequence of the virulent Office International des Epizooties AHSV reference strains which are not adapted to cell culture. PMID- 26358587 TI - Genome Sequences of Klebsiella variicola Isolates from Dairy Animals with Bovine Mastitis from Newfoundland, Canada. AB - Klebsiella variicola was recently reported as an emerging and/or previously misidentified species associated with opportunistic infections in humans. Here, we report the draft genome sequences of K. variicola isolates from two animals with clinical mastitis from a dairy farm in Newfoundland, Canada. PMID- 26358588 TI - Draft Genome Sequence of a Bordetella pertussis Strain with the Virulence Associated Allelic Variant ptxP3, Isolated in Italy. AB - Despite a universal immunization program, pertussis has persisted and resurged, and is of particular concern for infants in terms of morbidity and mortality. Here, we report the genome sequence of a Bordetella pertussis strain with the virulence-associated allelic variant ptxP3, isolated from a 45-day-old infant. PMID- 26358589 TI - Genome Sequences of Two Strains of Salmonella enterica Serovar Enteritidis Isolated from Shell Eggs. AB - This report presents the complete genome sequences of two Salmonella enterica serovar Enteritidis strains bearing the pulsed-field gel electrophoresis profile JEGX01.0004, which were isolated from the internal contents of eggs. PMID- 26358590 TI - Draft Genome Sequences of Dickeya sp. Isolates B16 (NIB Z 2098) and S1 (NIB Z 2099) Causing Soft Rot of Phalaenopsis Orchids. AB - The genus Dickeya contains bacteria causing soft rot of economically important crops and ornamental plants. Here, we report the draft genome sequences of two Dickeya sp. isolates from rotted leaves of Phalaenopsis orchids. PMID- 26358591 TI - Complete Genome Sequence of Human Respiratory Syncytial Virus from Shanghai, China. AB - We report here the complete genome sequence of human respiratory syncytial virus isolated from an outpatient child with fever and respiratory symptoms in Shanghai, China, in 2014. Phylogenetic analysis showed that the full-length respiratory syncytial virus (RSV) genome sequence belongs to human RSV (HRSV) group A. PMID- 26358592 TI - Draft Genome Sequences of Three Chromobacterium subtsugae Isolates from Wild and Cultivated Cranberry Bogs in Southeastern Massachusetts. AB - Chromobacterium subtsugae was isolated from cranberry bogs in Massachusetts. While it is unknown what environmental role these bacteria play in bog soils, they hold potential as biological control agents against the larvae of insect pests. Potential virulence genes were identified, including the violacein synthesis pathway, siderophores, and several chitinases. PMID- 26358593 TI - Complete Genome Sequence of the Clinical Strain Acinetobacter baumannii R2090 Carrying the Chromosomally Encoded Metallo-beta-Lactamase Gene blaNDM-1. AB - Acinetobacter baumannii is an emerging human pathogen causing nosocomial and community-acquired infections. Here, we present the complete genome sequence of the clinical A. baumannii strain R2090 carrying the metallo-beta-lactamase gene blaNDM-1 in its chromosome within the transposon Tn125. PMID- 26358594 TI - Complete Genome Sequences of Lineage IV Peste des Petits Ruminants Viruses from the Indian Subcontinent. AB - The complete genome sequences of two virulent lineage IV peste des petits ruminants viruses (PPRVs) isolated from clinically infected goats in the Indian subcontinent are reported here. This is the first report of a complete genome sequence of a virulent PPRV isolate from India in recent decades. PMID- 26358595 TI - Genome Sequences of Two Multidrug-Resistant Acinetobacter baumannii Clinical Strains Isolated from Southern India. AB - Acinetobacter baumannii is an emerging nosocomial pathogen causing infections worldwide. In this study, we determined the genome sequences of two multidrug resistant A. baumannii clinical strains isolated from a hospital in southern India. Genome analyses indicate that both the strains harbor numerous horizontally transferred genetic elements and antibiotic resistance cassettes. PMID- 26358596 TI - Complete Genome Sequence and Methylome of Staphylococcus schleiferi, an Important Cause of Skin and Ear Infections in Veterinary Medicine. AB - Staphylococcus schleiferi, a Gram-positive and coagulase-variable organism, is an opportunistic human pathogen and a major cause of skin and soft tissue infections in dogs. Here, we report the first S. schleiferi genome sequence and methylome from four canine clinical isolates. PMID- 26358597 TI - Complete Genome Sequence of the Type Strain Corynebacterium mustelae DSM 45274, Isolated from Various Tissues of a Male Ferret with Lethal Sepsis. AB - The complete genome of Corynebacterium mustelae DSM 45274 comprises 3,474,226 bp and 3,188 genes. Prominent niche and virulence factors are SpaBCA- and SpaDEF type pili with similarity to pilus proteins of Corynebacterium resistens and Corynebacterium urealyticum and an immunomodulatory EndoS-like endoglycosidase probably catalyzing the removal of distinct glycans from IgG antibodies. PMID- 26358598 TI - Whole-Genome Sequences of Two Rare Human Group C Rotavirus Strains Isolated from Two Cases of Acute Gastroenteritis. AB - This is a report of the complete genomic sequences of two rare group C rotavirus strains RVC/SZ94/CHN/2011 and RVC/SZ272/CHN/2011, isolated from two cases of acute gastroenteritis in Shenzhen, southern China, in 2011. These two strains display a close genetic relationship to 2007 Chinese strain YNR001 and 2008 Japanese strain BK0830. PMID- 26358599 TI - Draft Genome Sequences of Klebsiella variicola Plant Isolates. AB - Three endophytic Klebsiella variicola isolates-T29A, 3, and 6A2, obtained from sugar cane stem, maize shoots, and banana leaves, respectively-were used for whole-genome sequencing. Here, we report the draft genome sequences of circular chromosomes and plasmids. The genomes contain plant colonization and cellulases genes. This study will help toward understanding the genomic basis of K. variicola interaction with plant hosts. PMID- 26358600 TI - Draft Genome Sequence of Three Antibiotic-Resistant Leuconostoc mesenteroides Strains of Dairy Origin. AB - Leuconostoc mesenteroides is a lactic acid bacterium (LAB) commonly associated with fermented foods. Here, we report the genome sequence of three selected dairy strains, showing atypical antibiotic resistances (AR). Genome analysis provided a better understanding of the genetic bases of AR in Leuconostoc and its potential transferability among foodborne bacteria. PMID- 26358601 TI - Genome Sequence of Streptomyces caatingaensis CMAA 1322, a New Abiotic Stress Tolerant Actinomycete Isolated from Dried Lake Bed Sediment in the Brazilian Caatinga Biome. AB - The genome sequence of the first Streptomyces species isolated from the Brazilian Caatinga is reported here. Genes related to environmental stress tolerance were prevalent and included many secondary metabolic gene clusters. PMID- 26358602 TI - Genome Sequence of Pantoea ananatis Strain CFH 7-1, Which Is Associated with a Vector-Borne Cotton Fruit Disease. AB - Pantoea ananatis is a bacterium with versatile niches that vary from pathogenic to beneficial. We present the genome of strain CFH 7-1, which was recovered from a diseased greenhouse cotton boll previously caged with a field-collected cotton fleahopper (Pseudatomoscelis seriatus). These data will assist in deciphering the infection process. PMID- 26358603 TI - Draft Genome Sequence of Kerstersia gyiorum CG1, Isolated from a Leg Ulcer. AB - We report the first draft genome sequence of Kerstersia gyiorum from a leg ulcer of a patient with diabetes and osteomyelitis. The 3.94-Mb genome assembly included 3,428 annotated coding sequences with an N50 of 223,310 bp and a plasmid encoding a type IV secretion system gene and two antitoxin genes. PMID- 26358604 TI - Draft Genome Sequence of Type Strain Lysinibacillus xylanilyticus DSM 23493T. AB - Lysinibacillus xylanilyticus DSM 23493(T) is a Gram-positive, spore-forming bacterium. Here, we report the 5.22-Mb genome sequence of Lysinibacillus xylanilyticus DSM 23493(T), which will accelerate the application of degrading xylan and provide useful information for genomic taxonomy and phylogenomics of Bacillus-like bacteria. PMID- 26358605 TI - Draft Genome Sequence of Salmonella enterica subsp. enterica Serovar Napoli Strain SN310, Cause of a Multischool Outbreak in Milan, Italy, in 2014. AB - We report the draft genome sequence of Salmonella enterica subsp. enterica serovar Napoli strain SN310, isolated from a stool sample of an affected pupil during a multischool outbreak in 2014 in Milan, Italy. This represents the first reported draft genome sequence of the emerging serovar Napoli. PMID- 26358606 TI - Draft Genome Sequence of the Beer Spoilage Bacterium Megasphaera cerevisiae Strain PAT 1T. AB - The genus Megasphaera harbors important spoilage organisms that cause beer spoilage by producing off flavors, undesirable aroma, and turbidity. Megasphaera cerevisiae is mainly found in nonpasteurized low-alcohol beer. In this study, we report the draft genome of the type strain of the genus, M. cerevisiae strain PAT 1(T). PMID- 26358607 TI - Closed Genome Sequence of Octadecabacter temperatus SB1, the First Mesophilic Species of the Genus Octadecabacter. AB - The Gram-negative alphaproteobacterium Octadecabacter temperatus SB1 (DSM 26878) belongs to the marine Roseobacter clade. The genome of this strain is the smallest closed genome of the Roseobacter clade. O. temperatus SB1 is the first described nonpolar mesophilic isolate of the genus Octadecabacter and the type strain of the species. PMID- 26358608 TI - Complete Genome Sequences of Three Neisseria gonorrhoeae Laboratory Reference Strains, Determined Using PacBio Single-Molecule Real-Time Technology. AB - Neisseria gonorrhoeae, the etiological agent that causes the sexually transmitted infection gonorrhea, is a significant public health concern due to the emergence of antimicrobial resistance. We report the complete genome sequences of three reference isolates with varied antimicrobial susceptibility that will aid in elucidating the genetic mechanisms that confer resistance. PMID- 26358610 TI - Complete Genome Sequence of Papaya Ringspot Virus Isolated from Genetically Modified Papaya in Hainan Island, China. AB - The complete genome sequence (10,326 nucleotides) of a papaya ringspot virus isolate infecting genetically modified papaya in Hainan Island of China was determined through reverse transcription (RT)-PCR. The virus shares 92% nucleotide sequence identity with the isolate that is unable to infect PRSV resistant transgenic papaya. PMID- 26358609 TI - Draft Genome Sequence of a vanA-Type Vancomycin-Resistant Reference Strain, Enterococcus faecium ATCC 51559. AB - Vancomycin-resistant Enterococcus faecium has emerged as a multidrug-resistant pathogen in hospital settings. Here, we present the draft genome sequence of a high-level vancomycin-resistant strain, E. faecium ATCC 51559, which is employed as a standard laboratory vanA genotype-positive control strain for clinical and laboratory studies. PMID- 26358611 TI - Developments in Genetic and Epigenetic Data Protection in Behavioral and Mental Health Spaces. AB - The legal system has been preparing for an explosion of epigenetic issues in public health, environmental regulation and litigation. So far, this explosion has been muted, and for now epigenetic data protection merely seems to be "enjoying" the same technological and legal challenges experienced by other clinical and research data. However, three areas of development suggest where epigenetic data protection may prove problematic. This article examines these three issues, noting the rapid expansion of research based on EMR-sourced clinical data, the large number of data protection models that can apply to genetic data (including point-of-use prohibitions on discrimination and confidentiality), and the increasing and controversial dangers of deidentified information being reidentified. PMID- 26358612 TI - Unexpected divergence and lack of divergence revealed in continental Asian Cyornis flycatchers (Aves: Muscicapidae). AB - The flycatcher genus Cyornis (Aves: Muscicapidae) comprises 25 species with Oriental distributions. Their relationships are poorly known. We analyzed the phylogenetic relationships of 70 individuals from 12 species and several subspecies of Cyornis based on three mitochondrial genes and five nuclear introns, with special focus on Chinese and Vietnamese populations of the monotypic C. hainanus and polytypic C. rubeculoides. We found no support for inclusion of C. concretus in Cyornis. Deep divergences were observed among different subspecies of C. banyumas and C. rubeculoides. C. rubeculoides glaucicomans was also shown to have a highly distinctive song, and we propose that it is treated as a distinctive Chinese endemic species, C. glaucicomans. In contrast, the south Vietnamese C. rubeculoides klossi, which has a disjunct distribution from the other subspecies of C. rubeculoides, along with a recently discovered population in Guangdong Province (China) with several plumage features reminiscent of C. r. klossi, were indistinguishable in all loci analyzed from the phenotypically markedly different C. hainanus. More research is needed to elucidate the reasons for this unexpected pattern. PMID- 26358613 TI - Influence of mutation and recombination on HIV-1 in vitro fitness recovery. AB - The understanding of the evolutionary processes underlying HIV-1 fitness recovery is fundamental for HIV-1 pathogenesis, antiretroviral treatment and vaccine design. It is known that HIV-1 can present very high mutation and recombination rates, however the specific contribution of these evolutionary forces in the "in vitro" viral fitness recovery has not been simultaneously quantified. To this aim, we analyzed substitution, recombination and molecular adaptation rates in a variety of HIV-1 biological clones derived from a viral isolate after severe population bottlenecks and a number of large population cell culture passages. These clones presented an overall but uneven fitness gain, mean of 3-fold, respect to the initial passage values. We found a significant relationship between the fitness increase and the appearance and fixation of mutations. In addition, these fixed mutations presented molecular signatures of positive selection through the accumulation of non-synonymous substitutions. Interestingly, viral recombination correlated with fitness recovery in most of studied viral quasispecies. The genetic diversity generated by these evolutionary processes was positively correlated with the viral fitness. We conclude that HIV 1 fitness recovery can be derived from the genetic heterogeneity generated through both mutation and recombination, and under diversifying molecular adaptation. The findings also suggest nonrandom evolutionary pathways for in vitro fitness recovery. PMID- 26358614 TI - A codon model of nucleotide substitution with selection on synonymous codon usage. AB - The quality of phylogenetic inference made from protein-coding genes depends, in part, on the realism with which the codon substitution process is modeled. Here we propose a new mechanistic model that combines the standard M0 substitution model of Yang (1997) with a simplified model from Gilchrist (2007) that includes selection on synonymous substitutions as a function of codon-specific nonsense error rates. We tested the newly proposed model by applying it to 104 protein coding genes in brewer's yeast, and compared the fit of the new model to the standard M0 model and to the mutation-selection model of Yang and Nielsen (2008) using the AIC. Our new model provided significantly better fit in approximately 85% of the cases considered for the basic M0 model and in approximately 25% of the cases for the M0 model with estimated codon frequencies, but only in a few cases when the mutation-selection model was considered. However, our model includes a parameter that can be interpreted as a measure of the rate of protein production, and the estimates of this parameter were highly correlated with an independent measure of protein production for the yeast genes considered here. Finally, we found that in some cases the new model led to the preference of a different phylogeny for a subset of the genes considered, indicating that substitution model choice may have an impact on the estimated phylogeny. PMID- 26358615 TI - Detection of artificially induced vertical root fractures of different widths by cone beam computed tomography in vitro and in vivo. AB - AIMS: To compare the diagnostic accuracy of cone beam computed tomography (CBCT) for the detection of artificially induced vertical root fractures (VRFs) of different widths in vitro and in vivo. METHODOLOGY: Vertical root fractures were induced in 25 extracted nonendodontically treated single-rooted human teeth (maxillary first premolars, maxillary canines and mandibular incisors). Twenty teeth without VRFs served as a control group. CBCT scanning (3D Accuitomo 170) was performed in vitro and in vivo. For the in vivo scanning, teeth were autoclaved, embedded into bite plates, placed in sterile plastic bags and then inserted into the mouths of volunteers. Teeth with VRFs were sectioned into axial slices and examined using a stereomicroscope to measure the widths of the VRFs. Five observers assessed the presence of VRFs using axial CBCT. Values for sensitivity, specificity, accuracy and interexaminer agreement were calculated. RESULTS: The accuracy, specificity and sensitivity of CBCT were significantly higher in vitro than in vivo for VRFs with widths 50-150 MUm (P < 0.05). The sensitivity and accuracy of CBCT were significantly higher for the detection of VRFs with widths greater than 150 MUm in vivo and in vitro (P < 0.05). The accuracy of CBCT in vivo was 0.29 and 0.8 for fracture widths ranging from 50 to 150 MUm and wider than 150 MUm, respectively. No significant differences in CBCT specificity were found between VRF widths both in vitro and in vivo. The interexaminer reliability of the raters revealed a kappa value of 0.72, demonstrating substantial agreement. CONCLUSION: The detectability of VRFs by CBCT in vitro and in vivo was dependent upon fracture width. The accuracy of CBCT in detecting VRFs of 50-300 MUm width in vivo was significantly lower compared to the in vitro accuracy. PMID- 26358616 TI - Thermally activated surface oxygen defects at the perimeter of Au/TiO2: a DFT+U study. AB - Density functional theory calculations were performed to examine the formation of oxygen atom vacancies on three model surfaces namely, clean anatase TiO2(001) and, Au3 and Au10 clusters supported on anatase TiO2(001). On the Au/TiO2 systems, three different types of lattice oxygen atoms can be identified: the Ti O-Au bridge, the Ti-O-Ti bridge in the perimeter of the Au cluster and the Ti-O Ti bridge away from the Au cluster, the oxygen atoms on the clean surface. The variation in DeltaG degrees with temperature for surface O vacancy formation was calculated for these three situations using total-energy, vibrational structure and optimized geometries of the material surfaces and the O2 molecule. The calculations reveal that the O defect formation on the clean anatase TiO2(001) surface seems very difficult due to the large positive value of DeltaG degrees (290 kJ mol(-1)) from 0 to 650 K. However, the presence of the Au cluster on the TiO2 surface changes the surface chemistry of the TiO2 significantly. We observed that the trend in DeltaG degrees variation for the vacancy formation from the Ti O-Au bridge is the same as on Au3/TiO2 and Au10/TiO2 systems, almost constant with large positive values of DeltaG degrees around 250 and 350 kJ mol(-1), respectively. The DeltaG degrees for the perimeter defect formation (Ti-O-Ti bridge in the perimeter of the Au cluster) is smaller for Aun/TiO2 systems than the clean TiO2 surface, however, the vacancy formation is possible only for the Au10/TiO2 system (close to 506 K). Finally, extended calculations for other oxygen atoms on the Au10/TiO2 model reveal that the trend in DeltaG degrees variation is similar for all the interface or perimeter O atoms around the Au cluster with marginal differences in the numerical value of DeltaG degrees . Since, the surface O atoms are activated only in the presence of a particular sized Au, we propose that a Au catalyzed Mars-van Krevelen mechanism could be a possible reaction mechanism for CO oxidation on Au/TiO2 catalysts at slightly elevated temperatures. PMID- 26358617 TI - Quantitative structure-activity relationship: promising advances in drug discovery platforms. AB - INTRODUCTION: Quantitative structure-activity relationship (QSAR) modeling is one of the most popular computer-aided tools employed in medicinal chemistry for drug discovery and lead optimization. It is especially powerful in the absence of 3D structures of specific drug targets. QSAR methods have been shown to draw public attention since they were first introduced. AREAS COVERED: In this review, the authors provide a brief discussion of the basic principles of QSAR, model development and model validation. They also highlight the current applications of QSAR in different fields, particularly in virtual screening, rational drug design and multi-target QSAR. Finally, in view of recent controversies, the authors detail the challenges faced by QSAR modeling and the relevant solutions. The aim of this review is to show how QSAR modeling can be applied in novel drug discovery, design and lead optimization. EXPERT OPINION: QSAR should intentionally be used as a powerful tool for fragment-based drug design platforms in the field of drug discovery and design. Although there have been an increasing number of experimentally determined protein structures in recent years, a great number of protein structures cannot be easily obtained (i.e., membrane transport proteins and G-protein coupled receptors). Fragment-based drug discovery, such as QSAR, could be applied further and have a significant role in dealing with these problems. Moreover, along with the development of computer software and hardware, it is believed that QSAR will be increasingly important. PMID- 26358619 TI - From silicosis to silica hazards: An experiment in medicine, history, and the social sciences. PMID- 26358618 TI - Optimization of next-generation sequencing transcriptome annotation for species lacking sequenced genomes. AB - Next-generation sequencing methods, such as RNA-seq, have permitted the exploration of gene expression in a range of organisms which have been studied in ecological contexts but lack a sequenced genome. However, the efficacy and accuracy of RNA-seq annotation methods using reference genomes from related species have yet to be robustly characterized. Here we conduct a comprehensive power analysis employing RNA-seq data from Drosophila melanogaster in conjunction with 11 additional genomes from related Drosophila species to compare annotation methods and quantify the impact of evolutionary divergence between transcriptome and the reference genome. Our analyses demonstrate that, regardless of the level of sequence divergence, direct genome mapping (DGM), where transcript short reads are aligned directly to the reference genome, significantly outperforms the widely used de novo and guided assembly-based methods in both the quantity and accuracy of gene detection. Our analysis also reveals that DGM recovers a more representative profile of Gene Ontology functional categories, which are often used to interpret emergent patterns in genomewide expression analyses. Lastly, analysis of available primate RNA-seq data demonstrates the applicability of our observations across diverse taxa. Our quantification of annotation accuracy and reduced gene detection associated with sequence divergence thus provides empirically derived guidelines for the design of future gene expression studies in species without sequenced genomes. PMID- 26358620 TI - The feasibility of quantitative MRI of perivascular spaces at 7T. AB - BACKGROUND: Dilated brain perivascular spaces (PVSs) are found to be associated with many conditions, including aging, dementia, and Alzheimer's disease (AD). Conventionally, PVS assessment is mainly based on subjective observations of the number, size and shape of PVSs in MR images collected at clinical field strengths (<=3T). This study tests the feasibility of imaging and quantifying brain PVS with an ultra-high 7T whole-body MRI scanner. NEW METHOD: 3D high resolution T2 weighted brain images from healthy subjects (n=3) and AD patients (n=5) were acquired on a 7T whole-body MRI scanner. To automatically segment the small hyperintensive fluid-filling PVS structures, we also developed a quantitative program based on algorithms for spatial gradient, component connectivity, edge detection, k-means clustering, etc., producing quantitative results of white matter PVS volume densities. RESULTS: The 3D maps of automatically segmented PVS show an apparent increase in PVS density in AD patients compared to age-matched healthy controls due to the PVS dilation (8.0+/-2.1 v/v% in AD vs. 4.9+/-1.3 v/v% in controls, p<0.05). COMPARISON WITH EXISTING METHOD: We demonstrated that 7T provides sufficient SNR and resolution for quantitatively measuring PVSs in deep white matter that is challenging with clinical MRI systems (<=3T). Compared to the conventional visual counting and rating for the PVS assessment, the quantitation method we developed is automatic and objective. CONCLUSIONS: Quantitative PVS MRI at 7T may serve as a non-invasive and endogenous imaging biomarker for diseases with PVS dilation. PMID- 26358621 TI - Comparative Proteomic Insights into the Lactate Responses of Halophilic Salinicoccus roseus W12. AB - Extremophiles use adaptive mechanisms to survive in extreme environments, which is of great importance for several biotechnological applications. A halophilic strain, Salinicoccus roseus W12, was isolated from salt lake in Inner Mongolia, China in this study. The ability of the strain to survive under high sodium conditions (including 20% sodium lactate or 25% sodium chloride, [w/v]) made it an ideal host to screen for key factors related to sodium lactate resistance. The proteomic responses to lactate were studied using W12 cells cultivated with or without lactate stress. A total of 1,656 protein spots in sodium lactate-treated culture and 1,843 spots in NaCl-treated culture were detected by 2-dimensional gel electrophoresis, and 32 of 120 significantly altered protein spots (fold change > 2, p < 0.05) were identified by matrix-assisted laser-desorption ionization time-of-flight mass spectrometry. Among 21 successfully identified spots, 19 proteins were upregulated and 2 were downregulated. The identified proteins are mainly involved in metabolism, cellular processes and signaling, and information storage and processing. Transcription studies confirmed that most of the encoding genes were upregulated after the cells were exposed to lactate in 10 min. Cross-protecting and energy metabolism-related proteins played an important role in lactate tolerance for S. roseus W12. PMID- 26358622 TI - Expression of Shewanella frigidimarina fatty acid metabolic genes in E. coli by CRISPR/cas9-coupled lambda Red recombineering. AB - OBJECTIVE: To construct a clustered, regularly interspaced, short palindromic repeats (CRISPR)/cas9 system and use this system to obtain a recombinant Escherichia coli strain possessing the fatty acid metabolism genes from a lipid rich marine bacterium. RESULTS: The fatty acid regulatory transcription factor (fadR), delta9 (Delta(9) desaturase) and acetyl-CoA carboxylase (acc) genes were cloned from Shewanella frigidimarina. The fatty acid regulatory transcription factor (fadD) and phosphoenolpyruvate carboxylase inactivated strains were used to construct the fadR/delta9 and acc knock-in strains, which are both markerless and "scar"-less, and identified the change in fatty acid composition in the recombinant strains. There was no change in fatty acid composition between the wild-type strain and recombinant strains. All strains had 11:0, 12:0, 13:0, 14:0, 15:0, 16:0, 17:1, 17:0 and 18:0 fatty acids, with 16:0 and 18:0 fatty acids being dominant. The total lipid content of each recombinant strain was higher than the wild-type strain, with a maximum of 13.1 %, nearly 5.3 % higher than wild-type strain. CONCLUSION: The CRISPR/cas9 system, in conjunction with lambda-Red recombinases, can rapidly and efficiently edit the E. coli genome. The CRISPR/cas9 recombineering machinery can be modified to select biotechnologically relevant bacteria other than E. coli. PMID- 26358623 TI - Control of plasmonic nanoantennas by reversible metal-insulator transition. AB - We demonstrate dynamic reversible switching of VO2 insulator-to-metal transition (IMT) locally on the scale of 15 nm or less and control of nanoantennas, observed for the first time in the near-field. Using polarization-selective near-field imaging techniques, we simultaneously monitor the IMT in VO2 and the change of plasmons on gold infrared nanoantennas. Structured nanodomains of the metallic VO2 locally and reversibly transform infrared plasmonic dipole nanoantennas to monopole nanoantennas. Fundamentally, the IMT in VO2 can be triggered on femtosecond timescale to allow ultrafast nanoscale control of optical phenomena. These unique features open up promising novel applications in active nanophotonics. PMID- 26358625 TI - Effect of corticosteroids on cardiac function in growth-restricted fetuses. AB - OBJECTIVE: To determine the acute effects of corticosteroids on the cardiovascular system in growth-restricted fetuses. METHODS: This was a prospective cohort study conducted at a tertiary hospital between January 2011 and October 2013. Fetal cardiovascular function in fetuses with intrauterine growth restriction (IUGR) was assessed immediately before and 24 h after the first dose of betamethasone, administered in routine management of IUGR. Fetal arterial and venous Dopplers were assessed. Fetal cardiac function was evaluated by tissue Doppler echocardiography, with the assessment of both left and right ventricular function by calculating myocardial performance index (MPI') and E':A' ratios. Values were compared before and after exposure. RESULTS: Seventeen patients were included at a mean gestational age of 34 + 1 (range, 29 + 1 to 37 + 4) weeks. Fifteen fetuses were below the 5(th) percentile and two were below the 10(th) percentile for estimated fetal weight and abdominal circumference and all had no interval growth during a 2-week period. There was a decrease in right MPI' (from 0.56 to 0.47; P = 0.007) after corticosteroid exposure but no change in left MPI' (from 0.49 to 0.48). Right MPI' was higher than left MPI' before exposure (0.56 vs 0.49, respectively; P = 0.001), but not after exposure (P = 0.55). There was no change in left or right ventricular E':A' ratios and no difference was detected in umbilical artery, middle cerebral artery or ductus venosus pulsatility index following administration of corticosteroids. CONCLUSIONS: Corticosteroids altered right-sided, but not left-sided, tissue Doppler MPI' in IUGR fetuses, with no detectable change in arterial or venous Doppler pulsatility indices. Before exposure, the mean right MPI' was higher than the left. However, after exposure, there was no difference, suggesting that corticosteroids may reverse the negative effect of IUGR on fetal heart function. Large prospective studies with a larger sample size are needed to confirm this finding. Copyright (c) 2015 ISUOG. Published by John Wiley & Sons Ltd. PMID- 26358626 TI - Jens Andreasen 80 years young. PMID- 26358624 TI - Cytokinin-induced promotion of root meristem size in the fern Azolla supports a shoot-like origin of euphyllophyte roots. AB - The phytohormones cytokinin and auxin orchestrate the root meristem development in angiosperms by determining embryonic bipolarity. Ferns, having the most basal euphyllophyte root, form neither bipolar embryos nor permanent embryonic primary roots but rather an adventitious root system. This raises the questions of how auxin and cytokinin govern fern root system architecture and whether this can tell us something about the origin of that root. Using Azolla filiculoides, we characterized the influence of IAA and zeatin on adventitious fern root meristems and vasculature by Nomarski microscopy. Simultaneously, RNAseq analyses, yielding 36,091 contigs, were used to uncover how the phytohormones affect root tip gene expression. We show that auxin restricts Azolla root meristem development, while cytokinin promotes it; it is the opposite effect of what is observed in Arabidopsis. Global gene expression profiling uncovered 145 genes significantly regulated by cytokinin or auxin, including cell wall modulators, cell division regulators and lateral root formation coordinators. Our data illuminate both evolution and development of fern roots. Promotion of meristem size through cytokinin supports the idea that root meristems of euphyllophytes evolved from shoot meristems. The foundation of these roots was laid in a postembryonically branching shoot system. PMID- 26358627 TI - Comment on 'Temperamental and socioeconomic factors associated with traumatic dental injuries among children aged 0-17 years in the Swedish BITA study'. PMID- 26358628 TI - Reply from the Authors. PMID- 26358629 TI - Impact of the presence of noise on RR interval-based atrial fibrillation detection. AB - Atrial fibrillation (AF) is the most common cardiac arrhythmia, but is currently under-diagnosed since it can be asymptomatic. Early detection of AF could be highly beneficial for the prevention of stroke, which is one major risk associated with AF, with a five fold increase. mHealth applications have been recently proposed for early screening of paroxysmal AF. Several automatic AF detections have been suggested, and they are mostly based on features extracted from the RR interval time-series, since this is more robust to ambulatory noise than p-wave based algorithms. The RR interval features highlight the irregularity and unpredictability of the rhythm due to the chaotic electrical conduction through the AV node. Such approach has proved to be accurate on openly available databases. However, current techniques are limited by their assumption of almost perfect R peak detection, and RR time-series features are usually estimated from manual annotations. Analysis of the huge amount of data an mHealth application may create has to be automated, robust to noise, and should incorporate a confidence index based on an estimation of the signal quality. In this study, we present an in depth analysis of the performance of AF detection algorithms as a function of noise and QRS detection performance. We show a linear decrease of AF detection accuracy with respect to the SNR. Finally, we will demonstrate how the use of an automatic signal quality index can ensure a given level of performance in AF detection, more than 95% AF detection accuracy by analyzing segments with a median SQI over 0.8. PMID- 26358630 TI - Finessing incivility: The professional socialisation experiences of student nurses' first clinical placement, a grounded theory. AB - BACKGROUND: Clinical practice is where student nurses are socialised into a professional role and acquire the distinct behaviour, attitudes and values of the nursing profession. Getting it right at the outset can maximise the development of a professional identity and the transmission of robust value systems. OBJECTIVES: To explore the impact of the first clinical placement on the professional socialisation of adult undergraduate student nurses in the United Kingdom. DESIGN: Data of a longitudinal qualitative nature were collected and analysed using grounded theory. SETTINGS: First year student nurses in hospital ward placements comprising a rural District General Hospital and a large inner city Hospital kept daily unstructured diaries for six weeks. PARTICIPANTS: A total of 26 undergraduate adult student nurses were purposefully sampled between 2008 and 2010 before undertaking their initial clinical placement. METHODS: Data collection and analysis used grounded theory and the key question asked of the diarists 'tell me what it is like to be a first year nurse on a first placement' was theoretically adjusted during constant comparison and as the theory emerged. Ethical approval and consent was obtained. RESULTS: The theory of finessing incivility comprises a conceptual framework depicting how student nurses deal with professional incivility during their initial clinical placement and sustain a student identity. Being disillusioned with their role as worker rather than learner yields a sense of 'status dislocation'. Despite needing professional benevolence, they remain altruistic and seek recompense from significant others to negotiate for learning opportunities and relocate their student status. CONCLUSIONS: Despite the stressful transition into clinical practice rather than 'fit in', the student nurses want to belong as learners. His or her own resilience to learn nursing and be a professional student maintains their resolve, their altruism and strengthens their existing values to be benevolent towards an indifferent profession. This behaviour ultimately mirrors the social nature of the practice community. PMID- 26358631 TI - Factors affecting nursing students' incivility: As perceived by students and faculty staff. AB - BACKGROUNDS: Students' incivility in institutions of higher education is a serious issue that faces educators in performing their teaching duties. The negative impacts associated with uncivil classroom behaviors have been found to contribute to the disruption of the learning process and the classroom learning environment, and the deterioration of the faculty-student relationship. OBJECTIVES: This study assays the incivility level among nursing students, investigates factors affecting student nurses' incivility, and explores the relationship between students' uncivil behavior and factors affecting its occurrence based on the perceptions of students and faculty staff. A descriptive comparative research design included all nursing students (n=186) and faculty staff (n=66) in the Faculty of Nursing, Port Said University. A structured questionnaire was used to collect the data. RESULTS: The results of the study reflected that less than two thirds of students (60.2%) reported irresponsible behaviors, more than half (55.9%) expressed that they behave inappropriately, and 47.8% of them believed that they behave aggressively. The highest percentage of students (55.4%) recorded a high level of uncivil behavior, while faculty staff recorded a lower level regarding aggressive uncivil student behaviors. Both faculty staff and students agreed that a high level of incivility is affected by the studied factors, including issues related to environmental and study climate, faculty policies, political atmosphere, and faculty staff. CONCLUSION: Uncivil students' behavior interferes with academic achievement and leads to a declined curve of ethics for nursing students, who are to be considered a symbol of ethics when dealing with their patients. Based on the study results, activated implementation of faculty policies on uncivil behaviors is recommended. Also, there is an obvious need to train faculty staff members to deal with uncivil and bullying students. PMID- 26358632 TI - Nurse teacher candidates learned to use social media during the international teacher training course. AB - The purpose of this study was to describe the nurse teacher candidates' learning outcomes and experiences in social media during the international nurse teacher training course, Empowering learning environments in nursing education, Intensive Program (EleneIP). The pre-post research design was used. The data was collected before and after the course, with the questionnaire consisting of structured and open questions. Altogether, 24 nurse teacher candidates from four different European countries participated in the course and this study. The results showed that the knowledge of using social media applications increased during the course from 5.2 (range 1-9) to 8.1 (range 4-10), and their skills increased from 4.5 (range 1-8) to 7.6 (range 4-10).The main topics learnt during the course were divided in two categories: subjects of the course and teaching and learning methods. The students' experiences concerning the EleneIP course were positive in both categories. The international group created during EleneIP course also allowed the students to achieve another important aim, learning from a collaborative group the importance and possibilities of different learning environments, considering the cultural and social characteristics of each country participating in it. PMID- 26358633 TI - Response to Napolioni, V., MacMurray, J. Infectious diseases, IL6 174G>C polymorphism, and human development. Brain Behav. Immun. (2015), http://dx.doi.org/10.1016/j.bbi.2015.08.016. PMID- 26358634 TI - Femoral Neck Anteversion and Lesser Trochanteric Retroversion in Patients With Ischiofemoral Impingement: A Case-Control Magnetic Resonance Imaging Study. AB - PURPOSE: To assess the relationship between the femoral neck version (FNV) and lesser trochanteric version (LTV) in symptomatic patients with ischiofemoral impingement (IFI) as compared with asymptomatic hips. METHODS: The FNV and LTV of patients with symptomatic IFI who underwent magnetic resonance imaging assessment including a standardized femoral version study protocol were compared with those of patients with asymptomatic hips in this retrospective, observational study. Patients with isolated intra-articular pathology, prior hip fracture, and lesser trochanter deformity were excluded. The FNV, LTV, ischiofemoral space, and quadratus femoris space were evaluated on axial magnetic resonance imaging, as well as the angle between the LTV and the FNV. Independent t-tests were used to determine differences between groups. RESULTS: Data from 11 out 15 symptomatic patients and 250 out of 320 asymptomatic patients were analyzed. The mean ischiofemoral space (11.9 v 22.9 mm; P < .001; 95% confidence interval [CI], 6.9 to 15.2) and mean quadratus femoris space (7.2 mm v 14.9 mm; P < .001; 95% CI, 5.4 to 8.6) were significantly smaller in symptomatic patients versus asymptomatic patients. There was no difference in mean LTV between groups (-23.6 degrees v -24.2 degrees ; P = .8; 95% CI, -7.5 to 6.4), however, the mean FNV (21.7 degrees v 14.1 degrees ; P = .02; 95% CI, -14.2 to -1.1) and the angle between the FNV and LTV on average (45.4 degrees v 38.3 degrees ; P = .01; 95% CI, -12.9 to -1.3) were higher in symptomatic than in asymptomatic patients, with statistical significance. CONCLUSIONS: The femoral mean neck anteversion and the mean angle between the FNV and LTV are significantly higher in patients with symptomatic IFI. The mean LTV is not increased in patients with symptomatic ischiofemoral impingement as compared with those patients with asymptomatic hips. LEVEL OF EVIDENCE: Level III, diagnostic study. PMID- 26358637 TI - Plasma citrulline after small bowel transplantation: effect of time from transplantation, acute cellular rejection, and renal failure. AB - BACKGROUND: Plasma citrulline concentration (CIT) depends on its synthesis by enterocytes and its catabolism by renal tubules. To evaluate CIT applicability as a marker of acute cellular rejection (ACR) after intestinal transplantation (ITx), CIT was investigated according to time from ITx, episodes of ACR, and creatinine clearance (CrCl). METHODS: Twenty-four adult ITx recipients were prospectively studied. The results were compared with those of 19 healthy controls (HCs) and of 29 patients with chronic renal failure (CRF). RESULTS: In ITx recipients, CIT was lower than in HCs during the first two postoperative weeks; it then progressively increased and reached the range observed in HCs, approximately between the 31st and the 45th postoperative day. A positive association with postoperative days (R = 0.63; p < 0.0001) and a negative association with CrCl (R = -0.57; p < 0.0001) were observed. CIT was higher in patients with CRF than in HCs (p < 0.0001). CIT sensitivity and specificity in detecting ACR after the 45th postoperative day were 38% and 83%, using CIT threshold observed in HCs, and 69% and 77%, respectively, using CIT threshold adjusted for CRF degree. CONCLUSIONS: Adjusting CIT threshold for CRF degree almost doubled the sensitivity of CIT as a non-invasive marker of ACR in ITx recipients. PMID- 26358635 TI - Venom-gland transcriptome and venom proteome of the Malaysian king cobra (Ophiophagus hannah). AB - BACKGROUND: The king cobra (Ophiophagus hannah) is widely distributed throughout many parts of Asia. This study aims to investigate the complexity of Malaysian Ophiophagus hannah (MOh) venom for a better understanding of king cobra venom variation and its envenoming pathophysiology. The venom gland transcriptome was investigated using the Illumina HiSeqTM platform, while the venom proteome was profiled by 1D-SDS-PAGE-nano-ESI-LCMS/MS. RESULTS: Transcriptomic results reveal high redundancy of toxin transcripts (3357.36 FPKM/transcript) despite small cluster numbers, implying gene duplication and diversification within restricted protein families. Among the 23 toxin families identified, three-finger toxins (3FTxs) and snake-venom metalloproteases (SVMPs) have the most diverse isoforms. These 2 toxin families are also the most abundantly transcribed, followed in descending order by phospholipases A2 (PLA2s), cysteine-rich secretory proteins (CRISPs), Kunitz-type inhibitors (KUNs), and L-amino acid oxidases (LAAOs). Seventeen toxin families exhibited low mRNA expression, including hyaluronidase, DPP-IV and 5'-nucleotidase that were not previously reported in the venom-gland transcriptome of a Balinese O. hannah. On the other hand, the MOh proteome includes 3FTxs, the most abundantly expressed proteins in the venom (43 % toxin sbundance). Within this toxin family, there are 6 long-chain, 5 short-chain and 2 non-conventional 3FTx. Neurotoxins comprise the major 3FTxs in the MOh venom, consistent with rapid neuromuscular paralysis reported in systemic envenoming. The presence of toxic enzymes such as LAAOs, SVMPs and PLA2 would explain tissue inflammation and necrotising destruction in local envenoming. Dissimilarities in the subtypes and sequences between the neurotoxins of MOh and Naja kaouthia (monocled cobra) are in agreement with the poor cross-neutralization activity of N. kaouthia antivenom used against MOh venom. Besides, the presence of cobra venom factor, nerve growth factors, phosphodiesterase, 5'-nucleotidase, and DPP IV in the venom proteome suggests its probable hypotensive action in subduing prey. CONCLUSION: This study reports the diversity and abundance of toxins in the venom of the Malaysian king cobra (MOh). The results correlate with the pathophysiological actions of MOh venom, and dispute the use of Naja cobra antivenoms to treat MOh envenomation. The findings also provide a deeper insight into venom variations due to geography, which is crucial for the development of a useful pan-regional antivenom. PMID- 26358638 TI - Extensive rhabdomyosarcomatous differentiation in recurrent low-grade urothelial carcinoma of the bladder after transurethral resection: a case report. AB - INTRODUCTION: Sarcomatoid carcinoma of the urinary bladder is a rare bidirectional malignant neoplasm with epithelial and mesenchymal differentiation. The epithelial component is mainly high-grade urothelial carcinoma, and the mesenchymal component includes rhabdomyosarcoma. However, proper differential diagnosis of adult rhabdomyosarcomatous tumors of the bladder can be a challenge. Moreover, low-grade urothelial carcinoma as the epithelial component of sarcomatoid carcinoma has not been reported. CASE PRESENTATION: A 64-year-old Asian man with a history of transurethral resection of low-grade urothelial carcinoma of the bladder visited our department with complaints of frequent urination and macroscopic hematuria. Computed tomography and magnetic resonance imaging demonstrated a large mass located in the anterior wall of the bladder. Pathological diagnosis of transurethral biopsy was low-grade, non-invasive papillary urothelial carcinoma, and tumor tissue was removed by total cystectomy. Immunohistochemical studies and fluorescence in situ hybridization assay of the resected neoplastic tissue revealed extensive rhabdomyosarcomatous differentiation causing the formation of a large pedunculated polyp with a papillary appearance of recurrent low-grade urothelial carcinoma. No evidence of recurrence was detected during 2 years of follow-up without further treatment. CONCLUSIONS: Urothelial carcinoma of the urinary bladder with extensive rhabdomyosarcomatous differentiation is rare, but it should be considered in the differential diagnosis even when urothelial carcinoma coexisting with a rhabdomyosarcomatous component is low-grade and non-invasive. PMID- 26358636 TI - In vitro evaluation of adhesion/proliferation of human gingival fibroblasts on demineralized root surfaces by toluidine blue O in antimicrobial photodynamic therapy. AB - BACKGROUND: Antimicrobial photodynamic therapy (aPDT) in Dentistry has important effects as bacterial destruction in areas with periodontal disease. Some dyes applied in aPDT could present low pH and, consequently, result in tooth demineralization. This study evaluated demineralization produced by aPDT with toluidine blue O (TBO) at low pH and analyzed adhesion/proliferation of human gingival fibroblasts (HGF). METHODS: In the 1st phase, bovine enamel and root dentin fragments received 2 treatments: PDT4 group (TBO-100 MUg/ml-pH 4-60s) plus laser (660 nm, 45 J/cm(2), 1.08 J, 30 mW, 30 s, spot 0.024 cm(2), 1.25 W/cm(2), sweeping, non-contact) and CA group (citric acid plus tetracycline-pH 1-180 s). Surface hardness loss and tooth wear were statistically analyzed (Student's t test, ANOVA/Tukey, p<0.05). In the 2nd phase, human dentin fragments were divided in C (control group-scaling and root planing), PDT4 and CA. HGF (10(4), 5th passage) were cultured on these fragments for 24, 48 and 72 h and counted in scanning electron microscopy photographs. Number of HGF was analyzed using repeated-measures ANOVA and Tukey (p<0.05). RESULTS: Percentage of surface hardness loss was similar in dentin for PDT4 (71.5%) and CA (76.1%) (p>0.05) and higher in enamel for CA (68.0%) compared to PDT4 (34.1%) (p<0.05). In respect to wear, no difference was found between PDT4 (dentin: 12.58 MUm, enamel: 12.19 MUm respectively) and CA (dentin: 11.74 MUm and enamel: 11.03 MUm) (p>0.05). Number of HGF was higher after 72 h in CA group (2.66, p<0.05) compared to PDT4 (2.2) and C (1.33). CONCLUSION: PDT4 is not as aggressive as CA for enamel. However, dentin demineralized promoted by PDT4 does not stimulate HGF adhesion and proliferation as CA. PMID- 26358639 TI - Sequencing of complete mitochondrial genome of brown algal Saccharina sp. ye-F. AB - The complete sequence (37 657 bp) of the mitochondrial DNA (mtDNA) of the Saccharina sp. ye-F was determined using Illumina sequencing data (Illumina Inc., San Diego, CA). The genome contains 38 protein-coding genes (PCG), three ribosomal RNA (rRNA), and 25 transfer RNA (tRNA) genes that are typical of Saccharina mtDNA. A phylogenetic analysis based on the mitochondrial genomes of brown algae indicated that Saccharina sp. ye-F and Saccharina longissima, Saccharina japonica are the most closely related species, which strongly supports their close phylogenetic affinity. PMID- 26358641 TI - Urethral reconstruction with a 3D porous bacterial cellulose scaffold seeded with lingual keratinocytes in a rabbit model. AB - The goal of this study was to evaluate the effects of urethral reconstruction with a three-dimensional (3D) porous bacterial cellulose (BC) scaffold seeded with lingual keratinocytes in a rabbit model. A novel 3D porous BC scaffold was prepared by gelatin sponge interfering in the BC fermentation process. Rabbit lingual keratinocytes were isolated, expanded, and seeded onto 3D porous BC. BC alone (group 1, N = 10), 3D porous BC alone (group 2, N = 10), and 3D porous BC seeded with lingual keratinocytes (group 3, N = 10) were used to repair rabbit ventral urethral defects (2.0 * 0.8 cm). Scanning electron microscopy revealed that BC consisted of a compact laminate while 3D porous BC was composed of a porous sheet buttressed by a dense outer layer. The average pore diameter and porosity of the 3D porous BC were 4.23 +/- 1.14 MUm and 67.00 +/- 6.80%, respectively. At 3 months postoperatively, macroscopic examinations and retrograde urethrograms of urethras revealed that all urethras maintained wide calibers in group 3. Strictures were found in all rabbits in groups 1 and 2. Histologically, at 1 month postoperatively, intact epithelium occurred in group 3, and discontinued epithelium was found in groups 1 and 2. However, groups 2 and 3 exhibited similar epithelial regeneration, which was superior to that of group 1 at 3 months (p < 0.05). Comparisons of smooth muscle content and endothelia density among the three groups revealed a significant increase at each time point (p < 0.05). Our results demonstrated that 3D porous BC seeded with lingual keratinocytes enhanced urethral tissue regeneration. 3D porous BC could potentially be used as an optimized scaffold for urethral reconstruction. PMID- 26358640 TI - One, two or three? Probing the stoichiometry of membrane proteins by single molecule localization microscopy. AB - Probing the oligomeric state of abundant molecules, such as membrane proteins in intact cells, is essential, but has not been straightforward. We address this challenge with a simple counting strategy that is capable of reporting the oligomeric state of dense, membrane-bound protein complexes. It is based on single-molecule localization microscopy to super-resolve protein structures in intact cells and basic quantitative evaluation. We validate our method with membrane-bound monomeric CD86 and dimeric cytotoxic T-lymphocyte-associated protein as model proteins and confirm their oligomeric states. We further detect oligomerization of CD80 and vesicular stomatitis virus glycoprotein and propose coexistence of monomers and dimers for CD80 and trimeric assembly of the viral protein at the cell membrane. This approach should prove valuable for researchers striving for reliable molecular counting in cells. PMID- 26358643 TI - Ethical Issues Raised by Epigenetic Testing for Alcohol, Tobacco, and Cannabis. AB - Epigenetic testing is one of the most significant new technologies to provide insight into the behavioral and environmental factors that influence the development and reconfiguration of the human genetic code. This technology allows us to identify structural changes in the genome that occur due to exposure to a wide variety of substances including alcohol, tobacco, and cannabis. The information gained can be used to promote health but it also raises a variety of ethical, legal, and social issues. As society progresses in understanding the epigenetic mechanisms of substance use and addiction, there is an opportunity to use these use this knowledge to enable medical, behavioral, and environmental interventions to alleviate the burden of addiction. This article describes the ethical issues associated with use of epigenetic testing for alcohol, tobacco, and cannabis and the implications of this technology. A further review of the scientific basis for the relevance of epigenetics is found in the accompanying article by Philibert and Erwin in this issue. PMID- 26358642 TI - Impact of male partner's awareness and support for contraceptives on female intent to use contraceptives in southeast Nigeria. AB - BACKGROUND: Despite the growing body of evidence on use of modern contraceptives among women in sub-Saharan African countries, little is known about the broader context in which female decision-making concerning contraceptive use occurs, particularly the role of their male partners' awareness and support of modern contraceptives. METHODS: We conducted a cross-sectional survey of 2468 pregnant women and their male partners enrolled in the Healthy Beginning Initiative (HBI), an intervention to increase HIV testing among pregnant women in Enugu, southeast Nigeria. The aims of this study were to determine: 1) male partners' awareness of, and support for, female contraceptive methods, and 2) influence of male partners' contraceptive awareness and support on pregnant women's expressed desire to use contraception. We used logistic regression models to examine the association between male partners' awareness and support of modern contraceptives on their spouses' desire to use contraceptives. RESULTS: Men's awareness of, and support for, use of modern contraceptives were significantly associated with their female partners' desire to use contraception. A majority of the men who were aware of modern contraceptives (66.5 %) and those who supported their spouses' use of contraception (72.5 %) had partners who expressed a desire to use contraception. Men who were aware of female contraception were 3 times more likely to have spouses who desired to use contraception (AOR = 3.17, 95 % C.I: 2.70-3.75). In addition, men who showed support for their spouses' use of contraception were over 5 times more likely to have spouses who indicated a desire to use contraception (AOR = 5.76, 95 % C.I: 4.82-6.88). Living in a household of 5 or more people (AOR = 1.45, 95 % C.I: 1.23-1.72) and residing in an urban area (AOR = 0.81, 95 % C.I: 0.67-0.97) were also significantly associated with women's expressed desire to use modern contraception. CONCLUSION: Men's awareness of, and support for, use of modern contraceptives were markedly associated with their spouses' desire to use contraception. This underscores the need for men's involvement in programs that seek to address women's uptake of contraception in low and middle income countries. PMID- 26358644 TI - Prenatal stress and early life febrile convulsions compromise hippocampal genes MeCP2/REST function in mid-adolescent life of Sprague-Dawley rats. AB - Early life neuronal insults exacerbate the development of febrile seizures and can result in epigenetic changes in the hippocampus. The MeCP2 and REST genes play a pivotal role in cognition as both contribute to neuronal function. In this study, cognitive function and expression of the MeCP2 and REST genes in the hippocampus were investigated in four groups of Sprague Dawley rats offspring viz. (1) Normally reared treated with saline (NSS). (2) Prenatally stressed treated with saline (SS). (3) Normally reared with febrile seizures (NSFS). (4) Prenatally stressed with febrile seizures (SFS). Pregnant dams were subjected to 1h of restraint stress for 7days starting on gestational day 14. Following birth, a once-off exposure to saline injections or febrile seizure induction was conducted on postnatal day (PND) 14. Behavioural tests were conducted using the Morris-Water maze on PND 21 and 30. Our results showed a febrile seizure effect on learning and memory in the non-stressed animals. However, febrile seizures did not exacerbate learning deficits in the prenatally stressed animals. Gene analysis found a down-regulation in MeCP2 gene expression and an up-regulation of the REST gene in prenatally stressed animals. Exposure to febrile seizure resulted in down-regulation of both MeCP2 and REST gene expression in the non stressed animals, but febrile seizures did not exacerbate the stress effect on gene expression. This suggests that exposure to prenatal stress (SS) and febrile seizures (NSFS) may impair cognitive behavioural function. However, in the NSFS animals, there seems to be an attempt to counteract the effects of febrile seizures with time. PMID- 26358645 TI - Comparing the Toxicity of Water-Soluble Fractions of Biodiesel, Diesel and 5% Biodiesel/Diesel Blend on Oreochromis niloticus Using Histological Biomarkers. AB - This study estimated end compared the potential toxic effects of the water soluble fractions (WSF) of biodiesel (B100), diesel and the commercial biodiesel (B5) on Oreochromis niloticus. After a 24 h-exposition to WSF-0% (control) and WSF-serial concentrations of 4.6%, 10%, 22%, 46% and 100%, samples of gill and liver of the exposed fishes were fixed in Bouin's solution, processed, stained using hematoxylin/eosin and analyzed by light-microscopy. WSF-hydrocarbons and methanol contents, analyzed by gas chromatography, were checked against the occurrence of abnormal histopathological alterations. These were not found in the control and WSF-4.6% exposed fishes, while exposures to or above 10%-WSF resulted in histopathological alterations whose severity increased in a dose-dependent manner, being higher in fishes exposed to WSF-diesel, or WSF-B5 when compared to biodiesel. These results, which were corroborated by the chemical analyses, highlighted the histological technique as an appropriate diagnostic tool that can be used for the preservation of water bodies' quality. PMID- 26358646 TI - Interspecific and Spatial Comparisons of Perfluorinated Compounds in Bighead and Silver Carp in the Illinois River, Illinois, USA. AB - We examined perfluoroalkyl compounds (PFC) in bighead (BHCP; Hypophthalmichthys nobilis) and silver (SVCP; H. molitrix) carp from the Illinois River, Illinois, USA. Summed PFC concentrations in whole fish did not differ by species or river reach. Perfluorooctanesulfonate (PFOS) concentrations were much greater in whole fish (16.4 ng/g) than in fillets (3.4 ng/g). PFOS concentrations represented 35% 51% of total measured PFC concentrations in whole fish, and in fillets were weakly associated with carcass mass (R2=0.17, p=0.01) and % carcass lipid (R2=0.16, p=0.01). No such relationship was observed in whole fish. The relationship between concentrations of individual PFC congeners in whole fish and carcass mass or % lipid content varied by species. Our study demonstrated that filter-feeders such as BHCP and SVCP can accumulate measureable concentrations of PFC and these results are important for understanding the fate of these compounds in large river systems. PMID- 26358648 TI - Relationships Between Potentiation Effects After Ballistic Half-Squats and Bilateral Symmetry. AB - The purposes of this study were to examine the effect of ballistic concentric only half-squats (COHS) on subsequent squat-jump (SJ) performances at various rest intervals and to examine the relationships between changes in SJ performance and bilateral symmetry at peak performance. Thirteen resistance-trained men performed an SJ immediately and every minute up to 10 min on dual force plates after 2 ballistic COHS repetitions at 90% of their 1-repetition-maximum COHS. SJ peak force, peak power, net impulse, and rate of force development (RFD) were compared using a series of 1-way repeated-measures ANOVAs. The percent change in performance at which peak performance occurred for each variable was correlated with the symmetry index scores at the corresponding time point using Pearson correlation coefficients. Statistical differences in peak power (P = .031) existed between rest intervals; however, no statistically significant pairwise comparisons were present (P > .05). No statistical differences in peak force (P = .201), net impulse (P = .064), and RFD (P = .477) were present between rest intervals. The relationships between changes in SJ performance and bilateral symmetry after the rest interval that produced the greatest performance for peak force (r = .300, P = .319), peak power (r = -.041, P = .894), net impulse (r = .028, P = .927), and RFD (r = -.434, P = .138) were not statistically significant. Ballistic COHS may enhance SJ performance; however, the changes in performance were not related to bilateral symmetry. PMID- 26358647 TI - Pregnancy-induced changes in the pharmacokinetics of caffeine and its metabolites. AB - This study sought to assess the pharmacokinetic (PK) changes of caffeine and its CYP1A2 metabolites across the 3 trimesters of pregnancy. A prospective, multicenter PK study was conducted among 59 pregnant women (93.2% white) who were studied once during a trimester. One beverage with 30-95 mg caffeine was consumed, and a blood/urine sample was collected within 1 hour postingestion. Concentrations of caffeine and its primary metabolites were quantified from serum and urine by LC-MS/MS. There was a significant increase in dose-normalized caffeine serum and urine concentrations between the first and third trimesters (P < .05 and P < .01, respectively). Normalized theophylline concentrations also increased significantly in the third trimester in serum (P < .001) and in urine (P < .05). The caffeine urine/serum concentration ratio also increased in the last trimester (P < .05). No significant difference was found in normalized paraxanthine or theobromine concentrations. This study identified decreased caffeine metabolism and an increase in the active metabolite theophylline concentrations during pregnancy, especially in the third trimester, revealing evidence of the large role that pregnancy plays in influencing caffeine metabolism. PMID- 26358649 TI - Colloidal spirals in nematic liquid crystals. AB - One of the central experimental efforts in nematic colloids research aims to explore how the interplay between the geometry of particles along with the accompanying nematic director deformations and defects around them can provide a means of guiding particle self-assembly and controlling the structure of particle induced defects. In this work, we design, fabricate, and disperse low-symmetry colloidal particles with shapes of spirals, double spirals, and triple spirals in a nematic fluid. These spiral-shaped particles, which are controlled by varying their surface functionalization to provide tangential or perpendicular boundary conditions of the nematic molecular alignment, are found inducing director distortions and defect configurations with non-chiral or chiral symmetry. Colloidal particles also exhibit both stable and metastable multiple orientational states in the nematic host, with a large number of director configurations featuring both singular and solitonic nonsingular topological defects accompanying them, which can result in unusual forms of colloidal self assembly. Our findings directly demonstrate how the symmetry of particle generated director configurations can be further lowered, or not, as compared to the low point group symmetry of solid micro-inclusions, depending on the nature of induced defects while satisfying topological constraints. We show that achiral colloidal particles can cause chiral symmetry breaking of elastic distortions, which is driven by complex three-dimensional winding of induced topological line defects and solitons. PMID- 26358650 TI - Aluminum chain in Li2Al3H8(-) as suggested by photoelectron spectroscopy and ab initio calculations. AB - Group 13 elements are very rarely observed to catenate into linear chains and experimental observation of such species is challenging. Herein we report unique results obtained via combined photoelectron spectroscopy and ab initio studies of the Li2Al3H8(-) cluster that confirm the formation of an Al chain surrounded by hydrogen atoms in a very particular manner. Comprehensive searches for the most stable structure of the Li2Al3H8(-) cluster have shown that the global minimum isomer I possesses a geometric structure, which resembles the structure of propane, similar to the experimentally known Zintl-phase Cs10H[Ga3H8]3 compound featuring the propane-like [Ga3H8](3-) polyanions. Theoretical simulations of the photoelectron spectrum have demonstrated the presence of only one isomer (isomer I) in the molecular beam. Chemical bonding analysis of the Li2Al3H8(-) cluster has revealed two classical Al-Al sigma bonds constituting the propane-like kernel. PMID- 26358651 TI - Shape-designed frustration by local polymorphism in a near-equilibrium colloidal glass. AB - We show that hard, convex, lithographic, prismatic kite platelets, each having three 72 degrees vertices and one 144 degrees vertex, preferentially form a disordered and arrested 2D glass when concentrated quasi-statically in a monolayer while experiencing thermal Brownian fluctuations. By contrast with 2D systems of other hard convex shapes, such as squares, rhombs, and pentagons, which readily form crystals at high densities, 72 degrees kites retain a liquid like disordered structure that becomes frozen-in as their long-time translational and rotational diffusion become highly bounded, yielding a 2D colloidal glass. This robust glass-forming propensity arises from competition between highly diverse few-particle local polymorphic configurations (LPCs) that have incommensurate features and symmetries. Thus, entropy maximization is consistent with the preservation of highly diverse LPCs en route to the arrested glass. PMID- 26358652 TI - Breeding signatures of rice improvement revealed by a genomic variation map from a large germplasm collection. AB - Intensive rice breeding over the past 50 y has dramatically increased productivity especially in the indica subspecies, but our knowledge of the genomic changes associated with such improvement has been limited. In this study, we analyzed low-coverage sequencing data of 1,479 rice accessions from 73 countries, including landraces and modern cultivars. We identified two major subpopulations, indica I (IndI) and indica II (IndII), in the indica subspecies, which corresponded to the two putative heterotic groups resulting from independent breeding efforts. We detected 200 regions spanning 7.8% of the rice genome that had been differentially selected between IndI and IndII, and thus referred to as breeding signatures. These regions included large numbers of known functional genes and loci associated with important agronomic traits revealed by genome-wide association studies. Grain yield was positively correlated with the number of breeding signatures in a variety, suggesting that the number of breeding signatures in a line may be useful for predicting agronomic potential and the selected loci may provide targets for rice improvement. PMID- 26358653 TI - Reply to Lawson et al.: A synergistic approach to mental health research. PMID- 26358654 TI - A more precise look at context in autism. PMID- 26358656 TI - Intracellular delivery of nanocarriers and targeting to subcellular organelles. AB - INTRODUCTION: Recent trends in drug delivery indicate a steady increase in the use of targeted therapeutics to enhance the specific delivery of biologically active payloads to diseased tissues while avoiding their off-target effects. However, in most cases, the distribution of therapeutics inside cells and their targeting to intracellular targets still presents a formidable challenge. The main barrier to intracellular delivery is the translocation of therapeutic molecules across the cell membrane, and ultimately through the membrane of their intracellular target organelles. Another prerequisite for an efficient intracellular localization of active molecules is their escape from the endocytic pathway. AREAS COVERED: Pharmaceutical nanocarriers have demonstrated substantial advantages for the delivery of therapeutics and offer elegant platforms for intracellular delivery. They can be engineered with both intracellular and organelle-specific targeting moieties to deliver encapsulated or conjugated cargoes to specific sub-cellular targets. In this review, we discuss important aspects of intracellular drug targeting and delivery with a focus on nanocarriers modified with various ligands to specifically target intracellular organelles. EXPERT OPINION: Intracellular delivery affords selective localization of molecules to their target site, thus maximizing their efficacy and safety. The advent of novel nanocarriers and targeting ligands as well as exploration of alternate routes for the intracellular delivery and targeting has prompted extensive research, and promises an exciting future for this field. PMID- 26358655 TI - Extra-hepatic manifestations associated with hepatitis E virus infection: a comprehensive review of the literature. AB - BACKGROUND AND AIMS: Hepatitis E virus (HEV) infection is a significant public health problem that afflicts almost 20 million individuals annually and causes acute liver injury in 3.5 million, with approximately 56 000 deaths. As with other viral hepatitides, extra-hepatic manifestations could represent an important aspect of this infection. The spectrum of these manifestations is still emerging. Acute pancreatitis and neurological, musculoskeletal, hematological, renal, and other immune-mediated manifestations have been described. The aim of this article is to comprehensively review the published literature of extra hepatic manifestations associated with HEV infection. DATA SOURCES: We searched the PubMed database using the MeSH term "hepatitis E" and each of the extra hepatic manifestations associated with HEV infection. No language or date restrictions were set in these searches. Searches retrieving articles with non-A, non-B hepatitis were excluded. Additional articles were identified through the reference lists of included articles. RESULTS: Several extra-hepatic manifestations associated with HEV infection have been published. The temporal association between some extra-hepatic manifestations and HEV infection and the exclusion of other possible etiologies suggests that HEV infection could have caused some of them. According to the available data, HEV infection appears to be strongly associated with acute pancreatitis, neurological disorders (with primarily dominant peripheral nerve involvement, most commonly manifested as Guillain-Barre syndrome, followed by neuralgic amyotrophy), hematological diseases (hemolytic anemia due to glucose phosphate dehydrogenase deficiency, and severe thrombocytopenia), glomerulonephritis, and mixed cryoglobulinemia. More data are needed to clarify whether an association exists with musculoskeletal or other immune-mediated manifestations. CONCLUSIONS: HEV infection should be considered in patients with acute pancreatitis, Guillain-Barre syndrome, neuralgic amyotrophy, hemolytic anemia due to glucose phosphate dehydrogenase deficiency, severe thrombocytopenia, glomerulonephritis, and mixed cryoglobulinemia. Alternatively, signs and symptoms of these conditions should be sought in patients with acute or chronic HEV infection. More data are needed to confirm the role of HEV in other extra-hepatic disorders. PMID- 26358657 TI - Nicotinamide phosphoribosyltransferase (NAMPT/PBEF/visfatin) is a tumoural cytokine released from melanoma. AB - High plasma levels of nicotinamide phosphoribosyltransferase (NAMPT), traditionally considered an intracellular enzyme with a key role in NAD synthesis, have been reported in several oncological, inflammatory and metabolic diseases. We now show that eNAMPT can be actively released by melanoma cells in vitro. We analysed the mechanisms of its release, and we found both classical and non-classical pathway involvement. eNAMPT released by melanoma cells, in our hands, has paracrine and autocrine effects: it activates MAPK, AKT and NF-kappaB pathways and increases colony formation in anchorage-independent conditions. eNAMPT also induces M1 polarization in human monocytes. Last, we demonstrate, for the first time in any cancer type, that eNAMPT levels in plasma of tumour-bearing mice increase and that this increase can be reconducted to the tumour itself. This provides an important cue on previous observations that eNAMPT is increased in patients with cancer. Moreover, silencing NAMPT in melanoma cells leads to a reduction in the tumour growth rate. Our findings extend the basis to consider eNAMPT as a cytokine involved in tumour progression. PMID- 26358658 TI - Trends of occupational fatalities involving machines, United States, 1992-2010. AB - BACKGROUND: This paper describes trends of occupational machine-related fatalities from 1992-2010. We examine temporal patterns by worker demographics, machine types (e.g., stationary, mobile), and industries. METHODS: We analyzed fatalities from Census of Fatal Occupational Injuries data provided by the Bureau of Labor Statistics to the National Institute for Occupational Safety and Health. We used injury source to identify machine-related incidents and Poisson regression to assess trends over the 19-year period. RESULTS: There was an average annual decrease of 2.8% in overall machine-related fatality rates from 1992 through 2010. Mobile machine-related fatality rates decreased an average of 2.6% annually and stationary machine-related rates decreased an average of 3.5% annually. Groups that continued to be at high risk included older workers; self employed; and workers in agriculture/forestry/fishing, construction, and mining. CONCLUSION: Addressing dangers posed by tractors, excavators, and other mobile machines needs to continue. High-risk worker groups should receive targeted information on machine safety. PMID- 26358660 TI - Accumulation of organic C components in soil and aggregates. AB - To explore soil organic carbon (SOC) accumulation mechanisms, the dynamics of C functional groups and macroaggregation were studied synchronously through aggregate fractionation and (13)C NMR spectroscopy in sandy loam soil following an 18-year application of compost and fertilizer in China. Compared with no fertilizer control, both compost and fertilizer improved SOC content, while the application of compost increased macroaggregation. Fertilizer application mainly increased the levels of recalcitrant organic C components characterized by methoxyl/N-alkyl C and alkyl C, whereas compost application mainly promoted the accumulation of methoxyl/N-alkyl C, phenolic C, carboxyl C, O-alkyl C and di-O alkyl C in bulk soil. The preferential accumulation of organic C functional groups in aggregates depended on aggregate size rather than nutrient amendments. These groups were characterized by phenolic C and di-O-alkyl C in the silt + clay fraction, carboxyl C in microaggregates and phenolic C, carboxyl C and methoxyl/N alkyl C in macroaggregates. Thus, the differences in accumulated organic C components in compost- and fertilizer-amended soils were primarily attributable to macroaggregation. The accumulation of methoxyl/N-alkyl C in microaggregates effectively promoted macroaggregation. Our results suggest that organic amendment rich in methoxyl/N-alkyl C effectively improved SOC content and accelerated macroaggregation in the test soil. PMID- 26358659 TI - Alpha-tocopherol quinine ameliorates spatial memory deficits by reducing beta amyloid oligomers, neuroinflammation and oxidative stress in transgenic mice with Alzheimer's disease. AB - The pathologies of Alzheimer's disease (AD) is associated with soluble beta amyloid (Abeta) oligomers, neuroinflammation and oxidative stress. Decreasing the levels of Abeta oligomer, glial activation and oxidative stress are potential therapeutic approaches for AD treatment. We previously found alpha-tocopherol quinine (alpha-TQ) inhibited Abeta aggregation and cytotoxicity, decreased the release of inflammatory cytokines and reactive oxygen species (ROS) in vitro. However, whether alpha-TQ ameliorates memory deficits and other neuropathologies in mice or patients with AD remains unknown. In this study, we reported that orally administered alpha-TQ ameliorated memory impairment in APPswe/PS1dE9 transgenic mice, decreased oxidative stress and the levels of Abeta oligomer in the brains of mice, prevented the production of inducible nitric oxide synthase and inflammatory mediators, such as interleukin-6 and interleukin-1beta, and inhibited microglial activation by inhibiting NF-kappaB signaling pathway. These findings suggest that alpha-TQ has potential therapeutic value for AD treatment. PMID- 26358662 TI - Effects of riboflavin and amotosalen photoactivation systems for pathogen inactivation of fresh-frozen plasma on fibrin clot structure. AB - BACKGROUND: Fresh-frozen plasma (FFP) transfusion carries a risk of viral transmission from donor to recipient. Riboflavin (Mirasol) and amotosalen (Intercept) are two pathogen inactivation (PI) methods that may enhance the safety of FFP for transfusion. Our study investigated the effects of Mirasol and Intercept treatment on fibrin formation and clot structure. STUDY DESIGN AND METHODS: FFP underwent either Mirasol or Intercept treatment, and aliquots were taken before addition of the compound, before illumination (after addition of compound only), and after treatment (addition of compound plus illumination). All samples underwent turbidimetric analysis, lysis analysis, assessment of clot permeation, and analysis by laser scanning confocal microscopy. RESULTS: After treatment, there was a decrease in optical density of the fibrin network for Mirasol and Intercept, lag time to fibrin formation was prolonged for Mirasol and lysis time for Intercept, clot permeability was significantly decreased, and clot density was increased for both. CONCLUSIONS: Our study shows that plasma treated with Mirasol and Intercept produces denser clots consisting of thinner fibers and warrants further studies to evaluate the clinical significance of these structural changes in fibrin clot formation. PMID- 26358661 TI - Pointing and pantomime in wild apes? Female bonobos use referential and iconic gestures to request genito-genital rubbing. AB - Referential and iconic gesturing provide a means to flexibly and intentionally share information about specific entities, locations, or goals. The extent to which nonhuman primates use such gestures is therefore of special interest for understanding the evolution of human language. Here, we describe novel observations of wild female bonobos (Pan paniscus) using referential and potentially iconic gestures to initiate genito-genital (GG) rubbing, which serves important functions in reducing social tension and facilitating cooperation. We collected data from a habituated community of bonobos at Luikotale, DRC, and analysed n = 138 independent gesture bouts made by n = 11 females. Gestures were coded in real time or from video. In addition to meeting the criteria for intentionality, in form and function these gestures resemble pointing and pantomime-two hallmarks of human communication-in the ways in which they indicated the relevant body part or action involved in the goal of GG rubbing. Moreover, the gestures led to GG rubbing in 83.3% of gesture bouts, which in turn increased tolerance in feeding contexts between the participants. We discuss how biologically relevant contexts in which individuals are motivated to cooperate may facilitate the emergence of language precursors to enhance communication in wild apes. PMID- 26358663 TI - Correlation between Doppler flow patterns in growth-restricted fetuses and neonatal circulation. AB - OBJECTIVES: To investigate whether prenatal Doppler parameters in growth restricted fetuses are correlated with neonatal circulatory changes. METHODS: In 43 cases of suspected fetal growth restriction (FGR), serial Doppler measurements of umbilical artery (UA) and middle cerebral artery (MCA) pulsatility index (PI) were performed. The last measurement, closest to delivery (< 1 week before birth), was used for analysis. Neonatal circulation was assessed for 2 h/day on Days 1-5, 8 and 15 by near-infrared spectroscopy (NIRS) of the cerebral, renal and splanchnic regions. We calculated fractional tissue oxygen extraction (FTOE) as: (arterial oxygen saturation - NIRS value)/arterial oxygen saturation. The following ratios were calculated: cerebroplacental ratio (CPR; MCA-PI/UA-PI), cerebrorenal ratio (CRR; cerebral/renal FTOE) and cerebrosplanchnic ratio (CSR; cerebral/splanchnic FTOE). Spearman's rank correlation coefficient (rho) was calculated between prenatal Doppler parameters and neonatal NIRS variables. These analyses were carried out for the entire group, and separately for cases of early FGR (delivered < 34 weeks) and late FGR (>= 34 weeks). RESULTS: Fetal Doppler parameters correlated with neonatal NIRS variables on Days 1-3: UA-PI correlated with renal FTOE (Day 1: rho = 0.454, P < 0.01) and CRR (Day 1: rho = -0.517, P < 0.001). MCA-PI correlated with cerebral FTOE on Day 2 (rho = 0.469, P < 0.01), approached statistical significance on Day 3 but was not correlated on Day 1. CPR correlated with CRR (Day 1: rho = 0.474, P < 0.01). Most associations lost their statistical significance when early and late FGR subgroups were considered separately. CONCLUSION: Low MCA-PI and low CPR, indicating brain sparing before birth, are associated with low CRR after birth, indicating relatively greater blood flow to the cerebrum than to the renal region. Based on the results of this study, it could be speculated that if brain sparing is present in the fetal circulation, it persists during the first 3 days after birth. Copyright (c) 2015 ISUOG. Published by John Wiley & Sons Ltd. PMID- 26358664 TI - The use of pulse oximetry in evaluation of pulp vitality in immature permanent teeth. AB - BACKGROUND AND AIM: The current methods of pulp vitality assessment, either electric or thermal, are of limited use in children. Recently, traumatized and immature teeth may not respond to such methods and because such methods require subjective responses, it may not provide accurate results particularly in children. Pulse oximetry, an atraumatic approach, is used to measure oxygen saturation in vascular system. The aim of this study was to investigate the use of pulse oximetry to evaluate pulp vitality status in immature permanent teeth. METHODS AND MATERIALS: The study was conducted on 329 maxillary central and lateral incisors in children. The negative control group consisted of 10 root filled teeth. Systemic oxygen saturation was first measured on the thumb of the individual using a custom-made sensor. Oxygen saturation values of the teeth were then evaluated. The correlation between oxygen saturation measurement obtained from finger and tooth, and the correlation between oxygen saturation values and stage of root development were analyzed. A further comparison was made between the teeth with open and closed apex. RESULTS: Mean oxygen values recorded in the patient's finger were 97.17%, and mean oxygen values in the maxillary central and lateral incisors were 86.77% and 83/92%, respectively. There was no significant correlation between blood oxygen levels in the finger and in the teeth. (P > 0.05) There was a significant negative correlation between the stage of root development and the blood oxygen levels in the patients' teeth. (P < 0.05) Mean oxygen values in the teeth with open apex were significantly higher than the teeth with closed apex. (P < 0.001). CONCLUSION: Vital teeth provided consistent oxygen saturation readings, and non-vital teeth recorded no oxygen saturation values. During tooth development, the oxygen saturation values decreased. These findings confirm that the pulse oximetry is capable of detecting the pulpal blood flow and oxygen saturation. PMID- 26358665 TI - Observation versus prophylactic Ladd procedure for asymptomatic intestinal rotational abnormalities in heterotaxy syndrome: A systematic review. AB - BACKGROUND: The management of intestinal rotational abnormalities (IRA) in heterotaxy syndrome (HS) remains inconsistent. Because of the high incidence of malrotation in HS, screening of asymptomatic patients is standard of care in some institutions. The Ladd procedure is the treatment for malrotation, and has been reported to have high complication rates in HS patients. METHODS: We performed a systematic review of publications describing IRA in pediatric HS patients from January 1993 to present. The incidence of volvulus on surgical exploration was determined. Perioperative and long-term outcomes were analyzed to determine complication and mortality rates. RESULTS: Eleven retrospective studies describing 649 HS patients were identified. Of all patients with HS, 27% (176/649) underwent Ladd procedure. Only 1.2% (8/649) of HS patients included had volvulus. Postoperative complications occurred in 25 patients (14%), including a 10% incidence of small bowel obstruction. Perioperative and overall mortality rates after Ladd procedure were 3% and 21%, respectively. Six studies described mesenteric width, reporting 43% to have narrow mesentery. CONCLUSION: The Ladd procedure is not without significant morbidity and mortality in heterotaxy patients. Further prospective studies should investigate predictors of mesenteric width to spare the unnecessary morbidity of surgery in patients who are at low risk for volvulus. PMID- 26358666 TI - Moderate efficiency of clinicians' predictions decreased for blurred clinical conditions and benefits from the use of BRASS index. A longitudinal study on geriatric patients' outcomes. AB - OBJECTIVES: Accurate prognosis is an essential aspect of good clinical practice and efficient health services, particularly for chronic and disabling diseases, as in geriatric populations. This study aims to examine the accuracy of clinical prognostic predictions and to devise prediction models combining clinical variables and clinicians' prognosis for a geriatric patient sample. STUDY DESIGN AND SETTING: In a sample of 329 consecutive older patients admitted to 10 geriatric units, we evaluated the accuracy of clinicians' prognosis regarding three outcomes at discharge: global functioning, length of stay (LoS) in hospital, and destination at discharge (DD). A comprehensive set of sociodemographic, clinical, and treatment-related information were also collected. RESULTS: Moderate predictive performance was found for all three outcomes: area under receiver operating characteristic curve of 0.79 and 0.78 for functioning and LoS, respectively, and moderate concordance, Cohen's K = 0.45, between predicted and observed DD. Predictive models found the Blaylock Risk Assessment Screening Score together with clinicians' judgment relevant to improve predictions for all outcomes (absolute improvement in adjusted and pseudo-R(2) up to 19%). CONCLUSION: Although the clinicians' estimates were important factors in predicting global functioning, LoS, and DD, more research is needed regarding both methodological aspects and clinical measurements, to improve prognostic clinical indices. PMID- 26358667 TI - [Spontaneous bacterial peritonitis in patients with cirrhosis]. AB - Spontaneous bacterial peritonitis (SBP) is a severe complication occurring in patients with cirrhosis, and is associated with high mortality. Liver transplantation should be considered after a first episode of SBP. Gram-negative bacilli are the major cause of SBP, however there is an increasing trend of Gram positive cocci related SBP. Management includes empirical antibiotic treatment and albumin infusion. The choice of antibiotics depends on the site of acquisition (community-acquired vs nosocomial or health-care associated infection) and local resistance profile, due to the emergence of drug-resistant bacteria. Secondary prophylaxis is recommended after resolution of SBP and reduces recurrence and mortality. Primary prophylaxis in patients with low protein ascites (<15 g/L) should be restricted to patients with severe cirrhosis awaiting for liver transplantation. PMID- 26358668 TI - [Treatment of the acute diverticulitis: A systematic review]. AB - Acute diverticulitis is a common disease with increasing incidence. In most of cases, diagnosis is made at an uncomplicated stage offering a curative attempt under medical treatment and use of antibiotics. There is a risk of diverticulitis recurrence. Uncomplicated diverticulitis is opposed to complicated forms (perforation, abscess or fistula). Recent insights in the pathophysiology of diverticulitis, the natural history, and treatments have permitted to identify new treatment strategies. For example, the use of antibiotics tends to decrease; surgery is now less invasive, percutaneous drainage is preferred, peritoneal lavage is encouraged. Treatments of the diverticulitis are constantly evolving. In this review, we remind the pathophysiology and natural history, and summarize new recommendations for the medical and surgical treatment of acute diverticulitis. PMID- 26358669 TI - [From chronic disease to multimorbidity: Which impact on organization of health care]. AB - Healthcare systems are concerned with the growing prevalence of chronic diseases. Single disease approach, based on the Chronic Care Model, is known to improve specific indicators for the targeted disease. However, the co-existence of several chronic disease, or multimorbidity, within a same patient is the most frequent situation. The fragmentation of care, as consequence of the single disease approach, has negative impact on the patient and healthcare professionals. A person centred approach is a method addressing the combination of health issues of each patient. The coordination and synthesis role is key to ensure continuity of care for the patient within a network of healthcare professionals from several settings of care. This function is the main characteristic of an organized first level of care. PMID- 26358670 TI - [Media coverage of suicide: From the epidemiological observations to prevention avenues]. AB - Media coverage of suicide can result in increased morbi-mortality suicidal rates, due to an imitation process in those who are particularly vulnerable. This phenomenon is known as "Werther effect". Werther effect's magnitude depends on several qualitative and quantitative characteristics of the media coverage, in a dose-effect relationship. An extensive (in terms of audience and history repetition) and salient coverage (glorification of suicide, description of the suicidal method, etc.) increases the risk of contagion. Celebrities' suicide is particularly at risk of Werther effect. Media may also have a preventive role with respect to suicide. Indeed, according to "Papageno effect", journalists could, under certain conditions, help preventing suicide when reporting suicide stories. Two main theories in the field of social psychology have been proposed to account for Werther and Papageno effects: social learning theory and differential identification. Identification of Werther and Papageno effects uncovers new responsibilities and potentialities for the journalists in terms of public health. Their description provides a basis for promising targeted prevention actions. PMID- 26358672 TI - [Bariatric surgery, stomas and other digestive tract reductions: Insufficient data and recommendations to adapt medicines regimens in therapeutic practice]. AB - Surgery modifying digestive tract may alter drugs pharmacokinetics. To maintain concentrations of active substance in their therapeutic ranges, a dosage adjustment or change of drug may be necessary. This is particularly important when no pharmacological or pharmacodynamic parameter reflecting the medication effectiveness is easily measurable. Our objective was to gather the information and documentary tools that can guide prescription in these patients with rearranged digestive tract. We searched information on the documentary portals of French agencies, on gray literature, on MEDLINE and in the summaries product characteristics. No information was found on the website of French agencies, sparse data were identified in gray literature. Some document are discordant, most are imprecise. One hundred and ten studies or case reports referenced on MEDLINE describe 79 medications pharmacokinetics after gastrointestinal surgery. Four are not available in France. Six literature reviews were found. Four summaries of product characteristics provided information related to drug absorption. No documentary tool adapted to clinical routine exists. This unsatisfactory situation is a barrier to optimal patients care. Information is available. It is however necessary to gather under an ergonomic shape adapted to clinical routine, bringing the surgery type, pharmacokinetic changes induced and what to do about the dose adjustment. PMID- 26358671 TI - [Treatment of chronic hepatitis B virus infection and hepatocellular carcinoma prevention]. AB - Chronic hepatitis B virus (HBV) infection is a major public health problem. It concerns more than 240 million people over the world. Natural HBV history leads to hepatocellular carcinoma (HCC), developed on cirrhotic liver and/or by direct viral cacinogenesis. HCC incidence is estimated between 0,2 and 1% per year. The risk of HCC development showed a positive correlation with the level of HBV DNA in the sera. This virosuppression, obtained with interferon or analogs, can reduce the incidence of HCC development during chronic HBV infection. In case of HCC curative surgery, sustained virological response showed a protective effect on recurrence development. Guidelines suggest to treat every cirrhotic or highly replicative patients, and to screen every six months chronic HBs antigen carrier to prevent HCC development. PMID- 26358673 TI - [Treatment of osteolytic sequelae due to tuberculous spondylitis: About a case]. PMID- 26358674 TI - [Post-therapeutics features of hepatocellular carcinoma treated by stereotactic body radiation therapy]. PMID- 26358675 TI - [Factors modulating ageing and longevity: Linear or more complex relationships?]. AB - It is often accepted that various factors modulate ageing and longevity in a linear way, a higher/lower level of the factor delaying ageing and/or increasing longevity. However, many examples (e.g. the effects of diet restriction or antioxidants and of telomere attrition) show that this view can be wrong. For instance, mild stress has often positive effects on ageing and longevity, and severe stress opposite effects. The dose-response relationship is thus not linear but has an inverted U-shape. Therefore, in many cases, the concept of factors modulating ageing and longevity in a linear way should be rejected, and this has consequences for physicians' guidance. PMID- 26358676 TI - [Liver biopsy: A cause of little described complication]. PMID- 26358677 TI - [Occurrence of myelitis in a limited systemic scleroderma]. PMID- 26358678 TI - [Hyperemesis gravidarum: A review]. AB - Vomiting of pregnancy is a physiological symptom of the first trimester and is a frequent reason for consultation as well as hospitalization in the severe forms (hyperemesis gravidarum), which complicate 0.3 to 4% of the pregnancies and represent the first cause of hospitalization in the first trimester. Hyperemesis gravidarum may be responsible for a loss of weight with dehydration and/or hypokalemia. The use of scores such as PUQE-modified or NVPQOL may allow an objective and accurate assessment of symptoms and impairment of quality of life. Organic disease should be always eliminated and hospitalization may be necessary to effectively treat vomiting and correct any electrolyte disorders. PMID- 26358679 TI - Genome and Comparative Transcriptomics of African Wild Rice Oryza longistaminata Provide Insights into Molecular Mechanism of Rhizomatousness and Self Incompatibility. PMID- 26358680 TI - Disruption of the Sugar Transporters AtSWEET11 and AtSWEET12 Affects Vascular Development and Freezing Tolerance in Arabidopsis. PMID- 26358681 TI - Impact of different immunosuppressive regimens on the health-related quality of life following orthotopic liver transplantation. AB - BACKGROUND: The influence of immunosuppression on the recipients' quality of life (QoL) is of major importance after OLT and has not yet been evaluated. METHODS: The impact of different immunosuppression regimens after OLT was evaluated in 275 patients using the Short Form 36 (SF-36) survey. The following immunosuppressive strategies were compared: (a) CNI, (b) mTOR inhibitors, and (c) mTOR combined with CNI. All regimens were prescribed alone (mono) or in combination (+) with prednisolone and/or mycophenolate mofetil (MMF). RESULTS: Highest scores were evident in patients in the mTOR+ group. There were significantly higher values for general health perceptions (GH, p = 0.049), vitality (VIT, p = 0.020), and physical component summary (PCS, p = 0.041) when compared to CNImono and for GH (p = 0.042) and VIT (p = 0.043), when compared to mTORmono. Early conversion to mTOR inhibitors (two months after OLT), with a statistically significant improvement for the dimension role-emotional (RE, p = 0.027). DISCUSSION: mTOR inhibitor-based regimens appear to have beneficial effects on QoL after OLT, especially after an early conversion. PMID- 26358682 TI - The complete chloroplast genome of Eleutherococcus gracilistylus (W.W.Sm.) S.Y.Hu (Araliaceae). AB - Eleutherococcus gracilistylus is a plant species that is close to E. senticosus, a famous medicinal plant called Siberian ginseng. The complete chloroplast genome sequence of the E. gracilistylus was determined by de novo assembly using whole genome next generation sequences. The chloroplast genome of E. gracilistylus was 156 770 bp long and showed distinct four partite structures such as a large single copy region of 86 729 bp, a small single copy region of 18 175 bp, and a pair of inverted repeat regions of 25 933 bp. The overall GC contents of the genome sequence were 36.8%. The chloroplast genome of E. gracilistylus contains 79 protein-coding sequences, 30 tRNA genes, and four rRNA genes. The phylogenetic analysis with the reported chloroplast genomes confirmed close taxonomical relationship of E. gracilistylus with E. senticosus. PMID- 26358683 TI - Layer-by-layer films assembled from natural polymers for sustained release of neurotrophin. AB - Cortical neural prostheses (CNPs) hold great promise for paralyzed patients by recording neural signals from the brain and translating them into movement commands. However, these electrodes normally fail to record neural signals weeks to months after implantation due to inflammation and neuronal loss around the implanted neural electrodes. Sustained local delivery of neurotrophins from biocompatible coatings on CNPs can potentially promote neuron survival and attract the nearby neurons to migrate toward the electrodes to increase neuron density at the electrode/brain interface, which is important for maintaining the recording quality and long-term performance of the implanted CNPs. However, sustained release of neurotrophins from biocompatible ultrathin coatings is very difficult to achieve. In this study, we investigated the potential of several biocompatible natural polyanions including heparin, dextran sulfate, and gelatin to form layer-by-layer (LbL) assembly with positively charged neurotrophin nerve growth factor (NGF) and its model protein lysozyme, and whether sustained release of NGF and lysozyme can be achieved from the nanoscale thin LbL coatings. We found that gelatin, which is less negatively charged than heparin and dextran sulfate, showed the highest efficacy in loading proteins into the LbL films because other interactions in addition to electrostatic interactions were involved in LbL assembly. Sustained release of NGF and lysozymes for approximately 2 weeks was achieved from the gelatin-based LbL coatings. Released NGF maintained the bioactivity to stimulate neurite outgrowth from PC12 cells. Gelatin is generally recognized as safe by the FDA. Thus, the biocompatible LbL coating developed in this study is highly promising to be used for implanted CNPs to improve their long-term performance in human patients. PMID- 26358684 TI - Epigenetics and Child Psychiatry: Ethical and Legal Issues. AB - Epigenetics has the potential to revolutionize diagnosis and treatment in psychiatry, especially child psychiatry, as it may offer the opportunity for early detection and prevention, as well as development of new treatments. As with the previous introduction of genetic research in psychiatry, there is also the problem of unrealistic expectations and new legal and ethical problems. This article reviews the potential contributions and problems of epigenetic research in child psychiatry. Previous legal and ethical issues in genetic research serve as a guide to those in epigenetic research. Recommendations for safeguards and guidelines on the use of epigenetics with children and adolescents are outlined based on the identified issues. PMID- 26358686 TI - Anti-IgE for chronic urticaria - are children little adults after all? PMID- 26358687 TI - A farewell to Isil Barlan. PMID- 26358690 TI - Effect of renal impairment on the pharmacokinetics, pharmacodynamics, and safety of apixaban. AB - This open-label study evaluated apixaban pharmacokinetics, pharmacodynamics, and safety in subjects with mild, moderate, or severe renal impairment and in healthy subjects following a single 10-mg oral dose. The primary analysis determined the relationship between apixaban AUCinfinity and 24-hour creatinine clearance (CLcr ) as a measure of renal function. The relationships between 24-hour CLcr and iohexol clearance, estimated CLcr (Cockcroft-Gault equation), and estimated glomerular filtration rate (modification of diet in renal disease [MDRD] equation) were also assessed. Secondary objectives included assessment of safety and tolerability as well as international normalized ratio (INR) and anti-factor Xa activity as pharmacodynamic endpoints. The regression analysis showed that decreasing renal function resulted in modestly increased apixaban exposure (AUCinfinity increased by 44% in severe impairment with a 24-hour CLcr of 15 mL/min, compared with subjects with normal renal function), but it did not affect Cmax or the direct relationship between apixaban plasma concentration and anti factor Xa activity or INR. The assessment of renal function measured by iohexol clearance, Cockcroft-Gault, and MDRD was consistent with that determined by 24 hour CLcr . Apixaban was well tolerated in this study. These results suggest that dose adjustment of apixaban is not required on the basis of renal function alone. PMID- 26358689 TI - In vivo hepatogenic capacity and therapeutic potential of stem cells from human exfoliated deciduous teeth in liver fibrosis in mice. AB - INTRODUCTION: Liver transplantation is a gold standard treatment for intractable liver diseases. Because of the shortage of donor organs, alternative therapies have been required. Due to their potential to differentiate into a variety of mature cells, stem cells are considered feasible cell sources for liver regeneration. Stem cells from human exfoliated deciduous teeth (SHED) exhibit hepatogenic capability in vitro. In this study, we investigated their in vivo capabilities of homing and hepatocyte differentiation and therapeutic efficacy for liver disorders in carbon tetrachloride (CCl4)-induced liver fibrosis model mice. METHODS: We transplanted SHED into CCl4-induced liver fibrosis model mice through the spleen, and analyzed the in vivo homing and therapeutic effects by optical, biochemical, histological, immunological and molecular biological assays. We then sorted human leukocyte antigen-ABC (HLA-ABC)-positive cells from primary CCl4-damaged recipient livers, and analyzed their fusogenicity and hepatic characteristics by flow cytometric, genomic DNA, hepatocyte-specific gene assays. Furthermore, we examined the treatment effects of HLA-positive cells to a hepatic dysfunction by a secondary transplantation into CCl4-treated mice. RESULTS: Transplanted SHED homed to recipient livers, and expressed HLA-ABC, human hepatocyte specific antigen hepatocyte paraffin 1 and human albumin. SHED transplantation markedly recovered liver dysfunction and led to anti-fibrotic and anti-inflammatory effects in the recipient livers. SHED-derived HLA-ABC-positive cells that were sorted from the primary recipient liver tissues with CCl4 damage did not fuse with the host mouse liver cells. Sorted HLA-positive cells not only expressed human hepatocyte-specific genes including albumin, cytochrome P450 1A1, fumarylacetoacetase, tyrosine aminotransferase, uridine 5'-diphospho glucuronosyltransferase, transferrin and transthyretin, but also secreted human albumin, urea and blood urea nitrogen. Furthermore, SHED-derived HLA-ABC-positive cells were secondary transplanted into CCl4-treated mice. The donor cells homed into secondary recipient livers, and expressed hepatocyte paraffin 1 and human albumin, as well as HLA-ABC. The secondary transplantation recovered a liver dysfunction in secondary recipients. CONCLUSIONS: This study indicates that transplanted SHED improve hepatic dysfunction and directly transform into hepatocytes without cell fusion in CCl4-treated mice, suggesting that SHED may provide a feasible cell source for liver regeneration. PMID- 26358691 TI - Phase separation and self-assembly in a fluid of Mickey Mouse particles. AB - Recent developments in the synthesis of colloidal particles allow for control over shape and inter-particle interaction. One example, among others, is the so called "Mickey Mouse" (MM) particle for which the self-assembly properties have been previously studied yielding a stable cluster phase together with elongated, tube-like structures. Here, we investigate under which conditions a fluid of Mickey Mouse particles can yield phase separation and how the self-assembly behaviour affects the gas-liquid coexistence. We vary the distance between the repulsive and the attractive lobes (bond length), and the interaction range, and follow the evolution of the gas-liquid (GL) coexistence curve. We find that upon increasing the bond length distance the binodal line shifts to lower temperatures, and that the interaction range controls the transition between phase separation and self-assembly of clusters. Upon further reduction of the interaction range and temperature, the clusters assume an increasingly ordered tube-like shape, ultimately matching the one previously reported in literature. These results are of interest when designing particle shape and particle-particle interaction for self-assembly processes. PMID- 26358692 TI - T1 and T2 mapping for early diagnosis of dilated non-ischaemic cardiomyopathy in middle-aged patients and differentiation from normal physiological adaptation. AB - AIMS: The differential diagnosis of patients with early non-ischaemic dilated cardiomyopathy (DCM) and those with physiological adaptation to exercise ('athlete's heart') may be difficult as many of the morphological adaptations are shared in the two conditions. Increased physical fitness is becoming more common in later adulthood, a group in whom there may be even more diagnostic difficulty. We hypothesized that tissue characterization using cardiovascular magnetic resonance (CMR) T1 and T2 mapping would be able to differentiate between patients with left ventricular (LV) dilatation due to early DCM and exercisers. METHODS AND RESULTS: Fifty-eight middle-aged males [21 healthy controls, 21 males with a history of aerobic exercise and LV ejection fraction (LVEF) 45-55%, and 16 patients with DCM and LVEF 45-55%] underwent a CMR protocol including T1 and T2 mapping and calculation of extracellular volume (ECV) using a 1.5 T MRI scanner. Native T1, ECV, and T2 relaxation times were significantly increased in DCM patients compared with controls (native T1 1017 +/- 42 vs. 952 +/- 31 ms, P < 0.001; ECV 31.2 +/- 4.1 vs. 26.2 +/- 2.9%, P = 0.003; T2 55.9 +/- 4.4 vs. 52.9 +/ 3.3 ms, P = 0.05) and exercisers (native T1 957 +/- 32 ms, P < 0.001; ECV 26.3 +/- 3.6%, P = 0.004; T2 52.8 +/- 3.2 ms, P = 0.042). Using multivariable logistic regression, native T1 gave the best differentiation between exercisers and sedentary patients with early DCM (area under the curve 0.91). CONCLUSION: T1 and T2 mapping are potentially useful tools for differentiating between athlete's heart and patients with early DCM, and could be used whenever differentiation between these two phenotypes is inconclusive using standard imaging techniques. PMID- 26358693 TI - Reproducibility of functional aortic analysis using magnetic resonance imaging: the MESA. AB - AIMS: To assess the test-retest, intra- and inter-reader reliability of thoracic aorta measurements by magnetic resonance imaging (MRI). METHODS AND RESULTS: Twenty-five participants underwent aortic MRI twice over 13 +/- 7 days. All aortic variables from baseline and repeat MR were analysed using a semi-automated method by the ARTFUN software. To assess the inter-study reproducibility of aortic variables, we calculated intraclass correlation coefficient (ICC) for individual aortic measurements. Intra- and inter-observer variability was also assessed using the baseline MR data. Mean ascending aortic strain had moderate inter-study reproducibility (11.53 +/- 6.44 vs. 10.55 +/- 6.64, P = 0.443, ICC = 0.53, P < 0.01). Mean descending aortic strain and arch pulse wave velocity (PWV) had good inter-study reproducibility (descending aortic strain: 8.65 +/- 5.30 vs. 8.35 +/- 5.26, P = 0.706, ICC = 0.74, P < 0.001; PWV: 9.92 +/- 4.18 vs. 9.94 +/- 4.55, P = 0.968, ICC = 0.77, P < 0.001, respectively). All aortic variables had excellent intra- and inter-observer reproducibility (intra-: ICC range, 0.87 0.99, inter-: ICC range, 0.56-0.99, respectively). CONCLUSION: Inter-study reproducibility of all aortic variables was acceptable. Intra- and inter-observer reproducibility of all aortic variables was excellent. MRI can provide a repeatable method of measuring aortic structural and functional parameters. PMID- 26358694 TI - Differential incremental value of ultrasound carotid intima-media thickness, carotid plaque, and cardiac calcium to predict angiographic coronary artery disease across Framingham risk score strata in the APRES multicentre study. AB - AIMS: According to recent data, more accurate selection of patients undergoing coronary angiography for suspected coronary artery disease (CAD) is needed. From the Active PREvention Study multicentre prospective study, we further analyse whether carotid intima-media thickness (cIMT), carotid plaques (cPL), and echocardiographic cardiac calcium score (eCS) have incremental discriminatory and reclassification predictive value for CAD over clinical risk score in subjects undergoing coronary angiography, specifically depending on their low, intermediate, or high class of clinical risk. METHODS AND RESULTS: In eight centres, 445 subjects without history of prior CAD but with chest pain of recent onset and/or a positive/inconclusive stress test for ischaemia prospectively underwent clinically indicated elective coronary angiography after cardiac and carotid ultrasound assessments with measurements of cIMT, cPL, and eCS. The study population was divided into subjects at low (10%), intermediate (10-20%), and high (>20%) Framingham risk score (FRS). Ultrasound parameters were tested for their incremental value to predict CAD over FRS, in each pre-test risk category. No significant difference could be appreciated between the discrimination value of FRS and Diagnostic Imaging for Coronary Artery Disease score for the presence of CAD. eCS or cPL demonstrated significant incremental prediction over FRS, consistently in the three FRS categories (P < 0.01); this applied to both discrimination and reclassification, with the exception of high-risk subjects, in whom cPL was apparently not incremental over FRS, and eCS was only of borderline significance for better discrimination. CONCLUSIONS: Ultrasound eCS and cPL assessments were significant predictors of angiographic CAD in patients without prior CAD but with signs or symptoms suspect for CAD, independently and incrementally to FRS, across all pre-test risk probability strata, although in high-risk subjects, only eCS maintained an incremental value. The use of cIMT was not significantly incrementally useful in any FRS risk category. PMID- 26358695 TI - Differences in the prognostic relevance of myocardial ischaemia and scar by cardiac magnetic resonance in patients with and without diabetes mellitus. AB - AIMS: To evaluate the prognostic significance of myocardial ischaemia and scar in patients with and without diabetes mellitus (DM) who undergo dobutamine stress cardiac magnetic resonance (DCMR) and late gadolinium enhancement (LGE) imaging for known and suspected coronary artery diseases (CADs). METHODS AND RESULTS: A total of 1969 consecutive patients [age 63 +/- 12 years, 29% female, left ventricular ejection fraction = 59 +/- 12%] referred for a cardiac magnetic resonance (CMR) examination including DCMR and LGE with the suspicion of CAD or progression of CAD in three tertiary cardiac centres were analysed. Cardiac death and nonfatal myocardial infarction (MI) were registered as hard cardiac events. Patients with a revascularization procedure within the first 3 months after CMR were censored at the time of 'early' revascularization. Patients were followed for 3.2 +/- 1.5 years (median 2.9, interquartile range 2-4.3 years). In total, 90 (4.6%) cardiac deaths and MI were registered. Among them, 328 patients (16.6%) had diabetes. The proportion of dobutamine-induced wall motion abnormalities (DWMA) and LGE was higher in patients with DM when compared with those without DM (27 vs. 19% and 53.6 vs. 41.2%, respectively, P < 0.001 for both for proportions). Both DWMA and LGE were independent predictors of cardiac death and MI in patients without DM (HR for DWMA 8, CI 4.5-14.3, HR for LGE 2.1, CI 1.1 4.1) and with DM (HR for DWMA 8.6, CI 3.5-21, HR for LGE 4.5, CI 1.5-13.1). Tests for interaction showed that LGE more strongly influences prognosis in patients with than in those without DM (P = 0.03 for interaction), whereas the presence of DWMA is related to similarly poor outcomes in patients with and without DM (P = NS). CONCLUSION: Myocardial scar by LGE is a hallmark of markedly poorer outcome in patients with DM, while the presence of inducible myocardial ischaemia seems to be predictive both in patients with and without DM. Both markers surpass the predictive value of conventional atherogenic risk factors both in patients with and without DM. PMID- 26358697 TI - Female Sex Offenders: An Analysis of Crime Scene Behaviors. AB - The concept of the female sex offender (FSO) is a relatively new phenomenon within the social research literature. Studies of female rape, male rape, pedophilia, and juvenile sex offenders have suggested that different styles of offending are reflected in the different types of behaviors committed by offenders at the crime scene. These studies suggest that there are three distinct themes of behavior: Hostility, Impersonal, and Involvement. Multidimensional analysis is carried out on 35 crime scene behaviors of 73 FSOs from U.K. and U.S. law reports. The proposed framework was found to be a useful way of classifying FSOs with 84% displaying a dominant theme. These resulted in 52% classified as displaying Involvement, 17% as Control, and 15% as Hostility. Finally, the implications and suggestions for future research are discussed. PMID- 26358696 TI - Brain and Liver Headspace Aldehyde Concentration Following Dietary Supplementation with n-3 Polyunsaturated Fatty Acids. AB - Reactive oxygen species react with unsaturated fatty acids to form a variety of metabolites including aldehydes. Many aldehydes are volatile enough to be detected in headspace gases of blood or cultured cells and in exhaled breath, in particular propanal and hexanal which are derived from omega-3 and omega-6 polyunsaturated fatty acids, respectively. Aldehydes are therefore potential non invasive biomarkers of oxidative stress and of various diseases in which oxidative stress is thought to play a role including cancer, cardiovascular disease and diabetes. It is unclear, however, how changes in the abundance of the fatty acid precursors, for example by altered dietary intake, affect aldehyde concentrations. We therefore fed male Wistar rats diets supplemented with either palm oil or a combination of palm oil plus an n-3 fatty acid (alpha-linolenic, eicosapentaenoic, or docosahexaenoic acids) for 4 weeks. Fatty acid analysis revealed large changes in the abundance of both n-3 and n-6 fatty acids in the liver with smaller changes observed in the brain. Despite the altered fatty acid abundance, headspace concentrations of C1-C8 aldehydes, and tissue concentrations of thiobarbituric acid reactive substances, did not differ between the 4 dietary groups. Our data suggest that tissue aldehyde concentrations are independent of fatty acid abundance, and further support their use as volatile biomarkers of oxidative stress. PMID- 26358698 TI - Gender Wage Gap Accounting: The Role of Selection Bias. AB - Mulligan and Rubinstein (2008) (MR) argued that changing selection of working females on unobservable characteristics, from negative in the 1970s to positive in the 1990s, accounted for nearly the entire closing of the gender wage gap. We argue that their female wage equation estimates are inconsistent. Correcting this error substantially weakens the role of the rising selection bias (39 % versus 78 %) and strengthens the contribution of declining discrimination (42 % versus 7 %). Our findings resonate better with related literature. We also explain why our finding of positive selection in the 1970s provides additional support for MR's main hypothesis that an exogenous rise in the market value of unobservable characteristics contributed to the closing of the gender gap. PMID- 26358699 TI - Bayesian Probabilistic Projection of International Migration. AB - We propose a method for obtaining joint probabilistic projections of migration for all countries, broken down by age and sex. Joint trajectories for all countries are constrained to satisfy the requirement of zero global net migration. We evaluate our model using out-of-sample validation and compare point projections to the projected migration rates from a persistence model similar to the method used in the United Nations' World Population Prospects, and also to a state-of-the-art gravity model. PMID- 26358700 TI - Feminized Intergenerational Mobility Without Assimilation? Post-1965 U.S. Immigrants and the Gender Revolution. AB - Women in the United States have made significant socioeconomic advances over the last generation. The second generation of post-1965 immigrants came of age during this "gender revolution." However, assimilation theories focus mainly on racial/ethnic trajectories. Do gendered trajectories between and within groups better capture mobility patterns? Using the 1980 decennial census and the 2003 2007 Current Population Survey (CPS), we observe the socioeconomic status of Latino and Asian immigrant parents and their second-generation children 25 years later. We compare the educational, occupational, and earnings attainment of second-generation daughters and sons with that of their immigrant mothers and fathers. We simultaneously compare those socioeconomic trajectories with a U.S. born white, non-Latino reference group. We find that second-generation women experience greater status attainment than both their mothers and their male counterparts, but the earnings of second-generation women lag behind those of men. However, because white mainstream women experienced similar intergenerational mobility, many gaps between the second generation and the mainstream remain. These patterns remain even after we control for parenthood status. With feminized intergenerational mobility occurring similarly across race, the racial/ethnic gaps observed in 1980 narrow but persist into the next generation for many outcomes. Both gender and race shape mobility trajectories, so ignoring either leads to an incomplete picture of assimilation. PMID- 26358701 TI - Implementation of an HPV vaccination program in Eldoret, Kenya: results from a qualitative assessment by key stakeholders. AB - BACKGROUND: Cervical cancer strikes hard in low-resource regions yet primary prevention is still rare. Pilot projects have however showed that Human Papillomavirus (HPV) vaccination programs can attain high uptake. Nevertheless, a study accompanying a vaccination demonstration project in Eldoret, Kenya, revealed less encouraging outcomes: uptake during an initial phase targeting ten schools (i.e., 4000 eligible girls), was low and more schools had to be included to reach the proposed number of 3000 vaccinated girls. The previously conducted study also revealed that many mothers had not received promotional information which had to reach them through schools: teachers were sensitized by health staff and asked to invite students and parents for HPV vaccination in the referral hospital. In this qualitative study, we investigate factors that hampered promotion and vaccine uptake. METHODS: Focus group discussions (FGD) with teachers (4) and fathers (3) were organized to assess awareness and attitudes towards the vaccination program, cervical cancer and the HPV vaccine, as well as a FGD with the vaccinators (1) to discuss the course of the program and potential improvements. Discussions were recorded, transcribed, translated, and analyzed using thematic analysis In addition, a meeting with the program coordinator was set up to reflect upon the program and the results of the FGD, and to formulate recommendations for future programs. RESULTS: Cervical cancer was poorly understood by fathers and teachers and mainly linked with nonconforming sexual behavior and modern lifestyle. Few had heard about the vaccination opportunity: feeling uncomfortable to discuss cervical cancer and not considering it as important had hampered information flow. Teachers requested more support from health staff to address unexpected questions from parents. Non-uptake was also the result of distrust towards new vaccines. Schools entering the program in the second phase reacted faster: they were better organized, e.g., in terms of transport, while the community was already more familiarized with the vaccine. CONCLUSIONS: Close collaboration between teachers and health staff is crucial to obtain high HPV vaccine uptake among schoolgirls. Promotional messages should, besides providing correct information, tackle misbeliefs, address stigma and stress the priority to vaccinate all, regardless of lifestyle. Monitoring activities and continuous communication could allow for detection of rumors and unequal uptake in the community. PMID- 26358702 TI - Compression of the posterior fossa venous sinuses by epidural hemorrhage simulating venous sinus thrombosis: CT and MR findings. AB - BACKGROUND: Posterior fossa dural venous sinus thrombus is a well-described complication of head trauma, especially when fracture crosses the dural sinus grooves or in association with epidural hemorrhage. We have found that post traumatic posterior fossa epidural hematoma compressing a dural venous sinus can mimic dural venous thrombus. OBJECTIVE: To discuss the CT and MRI findings of posterior fossa epidural hemorrhages simulating sinus thrombosis, to make radiologists aware of this important imaging pitfall. MATERIALS AND METHODS: We describe radiologic findings in four children in whom a posterior fossa epidural hemorrhage mimicked dural venous sinus thrombus. Routine CT head and CT venography were obtained on Toshiba volume and helical CT scanners. MRI and MR venography were performed on a Philips scanner. RESULTS: In all cases there was medial displacement and compression of the posterior fossa dural venous sinuses without intraluminal thrombosis. The epidural hemorrhage was seen tracking along sinus grooves in the occipital bone, peeling the dura containing the sinuses from the calvarium and compressing the sinus, simulating thrombosis on axial CT views. CONCLUSION: Both venous sinus thrombosis and posterior fossa epidural hemorrhages in children are well-described complications of head trauma. Posterior fossa epidural hemorrhage can mimic a sinus thrombus by compressing and displacing the sinuses. It is important to recognize this pitfall because treatment of a suspected thrombus with anticoagulation can worsen epidural hemorrhage. PMID- 26358703 TI - Effect of controlled hypotension on regional cerebral oxygen saturation during rhinoplasty: a prospective study. AB - The aim of this study was to investigate the effect of controlled hypotension on cerebral oxygen saturation (rSO2) using near infrared spectroscopy (NIRS) and evaluation of postoperative cognitive function in patients undergoing rhinoplasty. Fifty adult patients who were scheduled for elective rhinoplasty surgery and required controlled hypotension were enrolled in this prospective study. Controlled hypotension was provided using a combination of propofol and remifentanil infusion supplemented with nitroglycerin infusion as necessary. rSO2 was evaluated during controlled hypotension by NIRS. Cerebral desaturation was observed in 5 out of 50 patients (10 %) during hypotensive anesthesia. The greatest decrease from baseline was 28 % when MAP was 57 mmHg. In both non desaturated and desaturated patients, postoperative MMSE scores were significantly lower than preoperative scores. There was a 4 % decrease in the non desaturated patients and a 7 % decrease in the desaturated patients when preoperative and postoperative MMSE scores were compared. A decline in cognitive function 1 day after surgery was observed in 23 patients (46 %) and in all patients with intraoperative cerebral desaturation. The current study showed that even if SpO2 is in the normal range, there might be a decrease of more than 20 % in cerebral oxygen saturation during controlled hypotension. PMID- 26358704 TI - Secretion of dengue virus envelope protein ectodomain from mammalian cells is dependent on domain II serotype and affects the immune response upon DNA vaccination. AB - Dengue virus (DENV) is currently among the most important human pathogens and affects millions of people throughout the tropical and subtropical regions of the world. Although it has been a World Health Organization priority for several years, there is still no efficient vaccine available to prevent infection. The envelope glycoprotein (E), exposed on the surface on infective viral particles, is the main target of neutralizing antibodies. For this reason it has been used as the antigen of choice for vaccine development efforts. Here we show a detailed analysis of factors involved in the expression, secretion and folding of E ectodomain from all four DENV serotypes in mammalian cells, and how this affects their ability to induce neutralizing antibody responses in DNA-vaccinated mice. Proper folding of E domain II (DII) is essential for efficient E ectodomain secretion, with DIII playing a significant role in stabilizing soluble dimers. We also show that the level of protein secreted from transfected cells determines the strength and efficiency of antibody responses in the context of DNA vaccination and should be considered a pivotal feature for the development of E based DNA vaccines against DENV. PMID- 26358705 TI - More doctors charged with manslaughter are being convicted, shows analysis. PMID- 26358707 TI - Multiple factors affect vaccination status among Indian children, finds study. PMID- 26358706 TI - In utero transmission and tissue distribution of chronic wasting disease associated prions in free-ranging Rocky Mountain elk. AB - The presence of disease-associated prions in tissues and bodily fluids of chronic wasting disease (CWD)-infected cervids has received much investigation, yet little is known about mother-to-offspring transmission of CWD. Our previous work demonstrated that mother-to-offspring transmission is efficient in an experimental setting. To address the question of relevance in a naturally exposed free-ranging population, we assessed maternal and fetal tissues derived from 19 elk dam-calf pairs collected from free-ranging Rocky Mountain elk from north central Colorado, a known CWD endemic region. Conventional immunohistochemistry identified three of 19 CWD-positive dams, whereas a more sensitive assay [serial protein misfolding cyclic amplification (sPMCA)] detected CWD prion seeding activity (PrPCWD) in 15 of 19 dams. PrPCWD distribution in tissues was widespread, and included the central nervous system (CNS), lymphoreticular system, and reproductive, secretory, excretory and adipose tissues. Interestingly, five of 15 sPMCA-positive dams showed no evidence of PrPCWD in either CNS or lymphoreticular system, sites typically assessed in diagnosing CWD. Analysis of fetal tissues harvested from the 15 sPMCA-positive dams revealed PrPCWD in 80 % of fetuses (12 of 15), regardless of gestational stage. These findings demonstrated that PrPCWD is more abundant in peripheral tissues of CWD exposed elk than current diagnostic methods suggest, and that transmission of prions from mother to offspring may contribute to the efficient transmission of CWD in naturally exposed cervid populations. PMID- 26358708 TI - Survival of patients with de-novo metastatic breast cancer: analysis of data from a large breast cancer-specific private practice, a university-based cancer center and review of the literature. AB - Approximately 6 % of patients with breast cancer are diagnosed with de-novo distant metastases. We set out to look at two cohorts of patients seen at breast cancer-specific practices, compare the results to other reports and larger databases, and see how advances in treatment have impacted overall survival (OS). The records from a large breast cancer oncology private practice and a second data set from the University of Miami/Sylvester Comprehensive Cancer Center (UM/SCCC) tumor database were, retrospectively, reviewed to identify patients with de-novo metastases. We included those patients identified to have metastatic disease within 3 months of diagnosis of a breast primary cancer. Patients diagnosed between 1996 and 2006 were chosen for our study population. The OS for the private practice was 41.0 months (46.0 for ER positive and 26.0 for ER negative) and 36.0 months for UM/SCCC (52 months for ER positive and 36 months for ER negative). ER negativity and CNS- or visceral-dominant disease were associated with a significantly worse prognosis within the private practice. Dominant site was associated with a significantly worse prognosis within the UM/SCCC database but with a trend also for ER negativity. Age and ethnicity did not contribute significantly to the survival of patients within either cohort. The median survival in both cohorts and most other reported series was larger than that seen in the surveillance, epidemiology, and end results program and the National Cancer Database. The median OS among patients with de-novo metastatic breast cancer treated within two breast-specific oncology practices was over 3 years, which appears better than larger, more inclusive databases and publications from earlier decades. PMID- 26358709 TI - Repeat sentinel node biopsy should be considered in patients with locally recurrent breast cancer. AB - Most patients with locally recurrent breast cancer undergo axillary lymph node dissection (ALND). However, repeat sentinel node biopsy (SNB) could provide regional nodal staging and obviate the need for standard ALND. The Sentinel Node and Recurrent Breast Cancer (SNARB) study is a Dutch nationwide registration study conducted to determine feasibility, aberrant drainage rates, and clinical consequences of repeat SNB. A total of 536 patients with locally recurrent non metastatic breast cancer underwent lymphatic mapping and repeat SNB in 29 Dutch hospitals. A repeat sentinel node (SN) was identified in 333 of 536 patients (62.1 %) and surgically harvested in 287 patients (53.5 %). Aberrant lymph drainage was observed in 180 (54.1 %) of the 333 patients, more often after previous ALND (81.9 %) than SNB (28.4 %; P < 0.001). In 230 patients (80.1 %), the retrieved SN was tumor negative; 17 SNs (5.9 %) contained a micrometastasis and 29 (10.1 %) a macrometastasis. Confirmation ALND in 31 repeat SN-negative patients revealed a macrometastasis in two patients (6.5 %). The negative predictive value (NPV) of repeat SNB was 93.6 %, and ALND was omitted in 109 of the 248 patients (44.0 %) with a negative repeat SN. In 29 of the 44 patients (63.0 %) with a positive SN, adjuvant treatment plans were altered based on the repeat SNB. Repeat SNB is a feasible procedure with a high NPV, leading to a change in management in a substantial proportion of patients. Therefore, repeat SNB should replace routine ALND and serve as the standard of care in recurrent breast cancer. PMID- 26358710 TI - Accuracy of frozen section, imprint cytology, and permanent histology of sub nipple tissue for predicting occult nipple involvement in patients with breast carcinoma. AB - The sub-nipple tissue (SNT) examination has been used by surgeons to preserve, or not, the nipple in nipple-sparing mastectomy. However, it is uncertain whether SNT evaluation can predict nipple involvement. The aim of this study was to evaluate the accuracy, sensitivity, specificity, PPV, and NPV of the intraoperative frozen section and imprint cytology, and permanent histology of SNT to predict the involvement of the nipple in breast carcinoma and to compare the three exams. A prospective study was performed with 68 consecutive breast carcinoma women who had undergone mastectomy or central segmentectomy (removing nipple-areolar complex). After surgery, the nipple-areolar complex was dissected simulating a nipple-sparing flap (ex vivo). The SNT was subsequently removed and submitted to frozen section, imprint cytology, and permanent histology. The nipple was examined separately by paraffin histopathology and was considered the gold standard. The occult nipple involvement rate was 11.7 %. The frozen section, cytology, and permanent histology of SNT presented accuracy 86.8, 76.5, and 86.8 %; sensitivity 50, 37.5, and 62.5 %; specificity 91.7, 81.7, and 90 %; PPV 44.4, 21.4, and 45.5 %; and NPV 93.2, 90.7, and 94.7 %, respectively. The accuracy of the frozen section was similar to that of permanent histology (p = 0.77) and both were better than cytology (p = 0.01). False negative rates were 6.8 % for frozen section, 9.3 % for cytology and 5.3 % for paraffin. SNT evaluation is a good method for predicting occult nipple involvement; the outcomes showed a good accuracy and low false negative rate for the frozen section, cytology, and permanent histology exams. When we compared the exams, the frozen section was similar to permanent histology and more accurate than imprint cytology. PMID- 26358711 TI - The clinical significance of internal mammary lymph node (IMLN) biopsy during autologous reconstruction in breast cancer patients. AB - The clinical significance of IMLN metastases in breast cancer is controversial. Although IMLN status is an integral part of current AJCC staging of breast cancer, the elective sampling of IMLN is not part of routine surgery for breast cancer. The purpose of this study was to determine the incidence of IMLN metastases, associated risk factors if any, and its impact on further management and outcome. We retrospectively studied 470 cases that underwent autologous reconstruction surgery between 2002 and 2014. Of 470 cases, 157 breast cancer cases had histology-confirmed IMLN removal during the reconstruction. Only 9 patients (6 %) showed IMLN metastases as compared to 45 (34 %) that showed axillary nodal metastases (p < 0.01). Interestingly, 4 patients had metastases limited to IMLN without any metastases to axillary nodes. IMLN metastasis was significantly associated with age <40 years, lymphovascular invasion, and negative PR status. IMLN metastasis resulted in upstaging of 2 patients from stage I to III, and 1 from stage II to III. Five patients received additional chest wall radiation to target the positive IMLNs. Nine of 157 (6 %) patients with IMLN removal during reconstruction had loco-regional recurrence/metastasis as compared to 20 of 293 (7 %) patients without IMLN removal (p > 0.05) (follow up, 1-134 months). The overall rate of IMLN metastases (6 %) is much lower than the rate of axillary node metastases. Selective biopsy of IMLNs in patients with breast cancer, especially if younger than 40 years, and with lymphovascular invasion and negative PR status, may guide adjuvant treatment. PMID- 26358712 TI - Accuracy of using Diagnosis Procedure Combination administrative claims data for estimating the amount of opioid consumption among cancer patients in Japan. AB - OBJECTIVE: The state of opioid consumption among cancer patients has never been comprehensively investigated in Japan. The Diagnosis Procedure Combination claims data may be used to measure and monitor opioid consumption among cancer patients, but the accuracy of using the Diagnosis Procedure Combination data for this purpose has never been tested. METHODS: We aimed to ascertain the accuracy of using the Diagnosis Procedure Combination claims data for estimating total opioid analgesic consumption by cancer patients compared with electronic medical records at Aomori Prefectural Central Hospital. We calculated percent differences between estimates obtained from electronic medical records and Diagnosis Procedure Combination claims data by month and drug type (morphine, oxycodone, fentanyl, buprenorphine, codeine and tramadol) between 1 October 2012 and 30 September 2013, and further examined the causes of discrepancy by reviewing medical and administrative charts between April and July 2013. RESULTS: Percent differences varied by month for drug types with small prescription volumes, but less so for drugs with larger prescription volumes. Differences also tended to diminish when consumption was compared for a year instead of a month. Total percent difference between electronic medical records and Diagnosis Procedure Combination data during the study period was -0.1% (4721 mg per year per hospital), as electronic medical records as baseline. Half of the discrepancy was caused by errors in data entry. CONCLUSION: Our study showed that Diagnosis Procedure Combination claims data can be used to accurately estimate opioid consumption among a population of cancer patients, although the same conclusion cannot be made for individual estimates or when making estimates for a group of patients over a short period of time. PMID- 26358713 TI - Automated Assessment of Patients' Self-Narratives for Posttraumatic Stress Disorder Screening Using Natural Language Processing and Text Mining. AB - Patients' narratives about traumatic experiences and symptoms are useful in clinical screening and diagnostic procedures. In this study, we presented an automated assessment system to screen patients for posttraumatic stress disorder via a natural language processing and text-mining approach. Four machine-learning algorithms-including decision tree, naive Bayes, support vector machine, and an alternative classification approach called the product score model-were used in combination with n-gram representation models to identify patterns between verbal features in self-narratives and psychiatric diagnoses. With our sample, the product score model with unigrams attained the highest prediction accuracy when compared with practitioners' diagnoses. The addition of multigrams contributed most to balancing the metrics of sensitivity and specificity. This article also demonstrates that text mining is a promising approach for analyzing patients' self-expression behavior, thus helping clinicians identify potential patients from an early stage. PMID- 26358714 TI - Brown Algae (Phaeophyceae) from the Coast of Madagascar: preliminary Bioactivity Studies and Isolation of Natural Products. AB - Eight species of brown algae (Phaeophyceae) from the coast of Madagascar have been investigated for their chemical constituents. Fucosterol (3) was obtained as the most abundant compound. The brown alga Sargassum ilicifolium was the source for the first isolation of the terpenoid C27-alcohol 1,1',2-trinorsqualenol (1) from marine sources. From S. incisifolium we isolated the highly unsaturated glycolipid 1-O-palmitoyl-2-O-stearidonoyl-3-O-beta-D-galactopyranosylglycerol (4) and we report the first full assignment of its (1)H and (13)C NMR data. Apo-9' fucoxanthinone (8) along with 24-ketocholesterol (5), (22E)-3beta-hydroxycholesta 5,22-dien-24-one (6), and saringosterol (7) were obtained from Turbinaria ornata. The crude extracts of all eight species of brown algae exhibited a pronounced antimicrobial activity against the Gram-positive bacteria Bacillus cereus, Staphylococcus aureus, and Streptococcus pneumoniae. PMID- 26358715 TI - Becoming a mother: Supported decision-making in context. AB - Little is known about how women with intellectual disabilities make decisions in relation to pregnancy. Social support is important for mothers with intellectual disabilities in many areas. This study explored how the support network influenced the decision-making of women with intellectual disabilities in relation to pregnancy. The study extended previous research to include the multiple perspectives of mothers, personal and professional support network. A model of decision-making was constructed, with implications of how services approach working with mothers with intellectual disabilities. Using a grounded theory methodology, three mothers with intellectual disabilities, two of their family members and six professionals were interviewed about their experiences of decision-making in relation to pregnancy. The results suggested that the quality of a woman's relationships were key to facilitating decision-making. The results highlighted the need for services to focus on creating supportive working relationships with mothers and other services involved in the parenting assessment process. PMID- 26358716 TI - Human parechovirus infections and child myositis cases associated with genotype 3 in Osaka City, Japan, 2014. AB - Human parechovirus (HPeV) infects humans early in life and typically causes asymptomatic or mild diseases such as gastrointestinal and respiratory illness but sometimes leads to more serious consequences in neonates and young infants. In 2014, we detected HPeV from 38 patients by real-time reverse transcription-PCR in Osaka City, Japan, and 33 HPeV strains were genotyped based on their VP1 sequences. HPeV genotype 3 (HPeV-3) was the most prevalent and accounted for 22 cases (66.7%) followed by nine HPeV-1 (27.3%), one HPeV-2 (3.0%) and one HPeV-4 (3.0%). Phylogenetic analysis revealed that detected HPeV-3 strains were divided into three genetically distinct groups. One was characterized by a novel single amino acid deletion mutation at the N terminus of the 2A protein as well as the VP1 sequence, whereas the others were closely related to HPeV-3 strains detected in Japan in either 2008 or 2011. These HPeV-3 groups were detected from patients with various symptoms including three myositis cases. Recent papers have demonstrated that HPeV-3 was the aetiological agent for epidemic myalgia exclusively among adults from Yamagata Prefecture in Japan. Here, we provide clinical details and episodes of three myositis patients including an adult and two children in Osaka City, Japan. Our results suggest that HPeV-3 is a causative agent of myositis not only in adults but also in children. PMID- 26358717 TI - Internal fixation of single mandibular fracture under mandibular nerve block. AB - OBJECTIVE: The aim of this study was to assess the results of open reduction and internal fixation (OR/IF) of isolated mandibular fracture under regional anesthesia using mandibular nerve block. PATIENTS AND METHODS: This prospective study was carried out on 44 patients who had isolated traumatic parasymphyseal mandibular fractures. All patients were managed by OR/IF by two titanium miniplates using manual maxillomandibular fixation (MMF). All patients were sedated by (0.05 mg/kg) midazolam and (2 MUg/kg) fentanyl. The patients were randomly classified into two groups: the control group (22 patients) treated under general anesthesia (GA) and the study group (22 patients) repaired under regional anesthesia. The results were assessed as regards dental occlusion, average intrinsic vertical mouth opening, actual operative time, complication, tolerance and patient's satisfaction, and postoperative hospital stay time. RESULTS: Both groups were matched for age and sex. There were no statistically significant differences of the postoperative complication, dental occlusion, and mouth opening between both groups. Duration for anesthesia induction, intubation, and anesthesia recovery was not needed in regional anesthesia. Regional anesthesia was tolerable and highly satisfactory in all patients with no intraoperative or postoperative anesthesia-related problems and no reported complications. CONCLUSION: Regional anesthesia can effectively replace GA in selected cases of mandibular fracture obviating the risks of GA. PMID- 26358718 TI - "Cultural brokerage" and beyond: piloting the role of an urban Aboriginal Mental Health Liaison Officer. AB - BACKGROUND: Suboptimal use of mental health services persists for Aboriginal and Torres Strait Islander peoples(1). Coupled with poorer life expectancy than other Australians, barriers to care have included poorly established partnership and communication among mental health services and Aboriginal peoples, and cultural insensitivity. As such, a goal of the Aboriginal mental health workforce is to engage their people and improve the social and emotional well-being of Aboriginal peoples. In 2013, the Northern Area Mental Health Service piloted a 0.8 full time equivalent position of an Aboriginal Mental Health Liaison Officer in an urban setting. Therefore, aims of this study were to describe the development of the role and stakeholder perceptions on how the role impacts on the typical journey of Aboriginal consumers engaging with mental health services. Meeting the aims may provide an exemplar for other mental health services. METHODS: An illustrative case study using quantitative and qualitative data collection was undertaken. Descriptive statistics were computed to profile consumers and referral pathways. Thematic analysis was used to profile key stakeholder perceptions of the role. RESULTS: The Aboriginal Mental Health Liaison Officer received 37 referrals over a 9 month period. The major source of referral was from an emergency department (49 %). Seventy-three percent of referrals by the Aboriginal mental health liaison officer at discharge were to community mental health teams. Thematic analysis of data on the development of the role resulted in two themes themes; (1) realisation of the need to improve accessibility and (2) advocating for change. The description of the role resulted in four themes; (1) the initiator: initiating access to the service, (2) the translator: brokering understanding among consumers and clinicians, (3) the networker: discharging to the community, and (4) the facilitator: providing cyclic continuity of care. CONCLUSIONS: The liaison component of the role was only a part of the multiple tasks the urban Aboriginal Mental Health Liaison Officer fulfils. As such, the role was positively described as influencing the lives of Aboriginal consumers and their families and improving engagement with health professionals in the mental health service in question. PMID- 26358719 TI - Asymmetric Wnt Pathway Signaling Facilitates Stem Cell-Like Divisions via the Nonreceptor Tyrosine Kinase FRK-1 in Caenorhabditis elegans. AB - Asymmetric cell division is critical during development, as it influences processes such as cell fate specification and cell migration. We have characterized FRK-1, a homolog of the mammalian Fer nonreceptor tyrosine kinase, and found it to be required for differentiation and maintenance of epithelial cell types, including the stem cell-like seam cells of the hypodermis. A genomic knockout of frk-1, allele ok760, results in severely uncoordinated larvae that arrest at the L1 stage and have an excess number of lateral hypodermal cells that appear to have lost asymmetry in the stem cell-like divisions of the seam cell lineage. frk-1(ok760) mutants show that there are excess lateral hypodermal cells that are abnormally shaped and smaller in size compared to wild type, a defect that could be rescued only in a manner dependent on the kinase activity of FRK-1. Additionally, we observed a significant change in the expression of heterochronic regulators in frk-1(ok760) mutants. However, frk-1(ok760) mutants do not express late, nonseam hypodermal GFP markers, suggesting the seam cells do not precociously differentiate as adult-hyp7 cells. Finally, our data also demonstrate a clear role for FRK-1 in seam cell proliferation, as eliminating FRK 1 during the L3-L4 transition results in supernumerary seam cell nuclei that are dependent on asymmetric Wnt signaling. Specifically, we observe aberrant POP-1 and WRM-1 localization that is dependent on the presence of FRK-1 and APR-1. Overall, our data suggest a requirement for FRK-1 in maintaining the identity and proliferation of seam cells primarily through an interaction with the asymmetric Wnt pathway. PMID- 26358721 TI - Heterotrophic Bacteria Show Weak Competition for Nitrogen in Mediterranean Coastal Waters (Thau Lagoon) in Autumn. AB - The importance of heterotrophic bacteria relative to phytoplankton in the uptake of ammonium and nitrate was studied in Mediterranean coastal waters (Thau Lagoon) during autumn, when the Mediterranean Sea received the greatest allochthonous nutrient loads. Specific inhibitors and size-fractionation methods were used in combination with isotopic (15)N tracers. NO3 (-) and NH4 (+) uptake was dominated by phytoplankton (60 % on average) during the study period, which included a flood event. Despite lower biomass specific NH4 (+) and NO3 uptake rates, free living heterotrophic bacteria contributed significantly (>30 %) to total microbial NH4 (+) and NO3 (-) uptake rates in low chlorophyll waters. Under these conditions, heterotrophic bacteria may be responsible for more than 50 % of primary production, using very little freshly produced phytoplankton exudates. In low chlorophyll coastal waters as reported during the present 3-month study, the heterotrophic bacteria seemed to depend to a greater extent on allochthonous N and C substrates than on autochthonous substrates derived from phytoplankton. PMID- 26358720 TI - Single-Nucleotide-Specific Targeting of the Tf1 Retrotransposon Promoted by the DNA-Binding Protein Sap1 of Schizosaccharomyces pombe. AB - Transposable elements (TEs) constitute a substantial fraction of the eukaryotic genome and, as a result, have a complex relationship with their host that is both adversarial and dependent. To minimize damage to cellular genes, TEs possess mechanisms that target integration to sequences of low importance. However, the retrotransposon Tf1 of Schizosaccharomyces pombe integrates with a surprising bias for promoter sequences of stress-response genes. The clustering of integration in specific promoters suggests that Tf1 possesses a targeting mechanism that is important for evolutionary adaptation to changes in environment. We report here that Sap1, an essential DNA-binding protein, plays an important role in Tf1 integration. A mutation in Sap1 resulted in a 10-fold drop in Tf1 transposition, and measures of transposon intermediates support the argument that the defect occurred in the process of integration. Published ChIP Seq data on Sap1 binding combined with high-density maps of Tf1 integration that measure independent insertions at single-nucleotide positions show that 73.4% of all integration occurs at genomic sequences bound by Sap1. This represents high selectivity because Sap1 binds just 6.8% of the genome. A genome-wide analysis of promoter sequences revealed that Sap1 binding and amounts of integration correlate strongly. More important, an alignment of the DNA-binding motif of Sap1 revealed integration clustered on both sides of the motif and showed high levels specifically at positions +19 and -9. These data indicate that Sap1 contributes to the efficiency and position of Tf1 integration. PMID- 26358722 TI - ceRNA in cancer: possible functions and clinical implications. AB - Competing endogenous RNAs (ceRNAs) are transcripts that can regulate each other at post-transcription level by competing for shared miRNAs. CeRNA networks link the function of protein-coding mRNAs with that of non-coding RNAs such as microRNA, long non-coding RNA, pseudogenic RNA and circular RNA. Given that any transcripts harbouring miRNA response element can theoretically function as ceRNAs, they may represent a widespread form of post-transcriptional regulation of gene expression in both physiology and pathology. CeRNA activity is influenced by multiple factors such as the abundance and subcellular localisation of ceRNA components, binding affinity of miRNAs to their sponges, RNA editing, RNA secondary structures and RNA-binding proteins. Aberrations in these factors may deregulate ceRNA networks and thus lead to human diseases including cancer. In this review, we introduce the mechanisms and molecular bases of ceRNA networks, discuss their roles in the pathogenesis of cancer as well as methods of predicting and validating ceRNA interplay. At last, we discuss the limitations of current ceRNA theory, propose possible directions and envision the possibilities of ceRNAs as diagnostic biomarkers or therapeutic targets. PMID- 26358723 TI - Sedation for gastroscopy: Is it an adequately understood and informed choice? AB - INTRODUCTION: Sedation uptake rates for oesophagogastroduodenoscopy (OGD) vary greatly. Issues concerning adequate information and consent have been raised. Additionally, patient comprehension of sedation options is inconsistent. METHODS: A closed ended questionnaire was created and delivered to assess patient understanding regarding sedation prior to OGD. The questionnaire was based on British Society of Gastroenterology guidelines. RESULTS: One hundred and eleven patients were recruited. 90 % of the sedated and 73 % of the unsedated patients were satisfied with their respective decisions (OR 0.283, *p = 0.01). 65 % were unaware of basic differences between conscious sedation and general anesthesia, and 37 % were unaware that driving is permitted after having throat spray alone. The most informed of the age groups had the lowest uptake of sedation and the least informed had the highest uptake. CONCLUSION: The decision to undergo gastroscopy with or without sedation is not a sufficiently informed one. This study highlights the need for the widespread dissemination of good quality information to inform patients better regarding sedation prior to OGD. PMID- 26358724 TI - Listeria meningitis complicating a patient with ulcerative colitis on concomitant infliximab and hydrocortisone. AB - Infliximab, a monoclonal antibody directed against tumour necrosis factor, is an effective therapy for moderate-to-severe ulcerative colitis and Crohn's disease. Uncommonly, serious opportunistic infections have occurred in patients after infliximab administration. Here, we describe meningitis caused by Listeria monocytogenes developing in a 37-year-old man with ulcerative colitis refractory to intravenous corticosteroids 10 days after receiving his first infusion of infliximab. With the increasing use of tumour necrosis factor-alpha-neutralizing agents, clinicians should be aware of the risk of opportunistic infections caused by L. monocytogenes in patients with inflammatory bowel disease following infliximab treatment. The half-life of infliximab is 9.5 days; therefore, patients tend to be more susceptible in the immediate period following infusion. Patients receiving anti-TNF therapy should be advised to avoid foods such as soft cheeses and unpasteurized dairy products. PMID- 26358725 TI - The Sternocleidomastoid Flap for Oral Cavity Reconstruction: Extended Indications and Technical Modifications. AB - PURPOSE: Several investigators have found that preserving the superior thyroid artery flap can considerably increase the survival rate of the sternocleidomastoid (SCM) flap. Nevertheless, they have recommended not cleaning the lymph nodes above level II for occipital artery preservation, which can leave risky metastatic lymph nodes and restrict the application of the SCM flap in patients with at least stage N1. The authors propose that preserving only the superior thyroid arteriovenous system is sufficient to ensure survival of the SCM flap and preserving the occipital artery is not necessary. They also propose preserving the cranial portion of the external jugular vein for improved venous return of the skin paddle. PATIENTS AND METHODS: This study retrospectively examined 20 patients with oral cancer (18 male, 2 female; 33 to 92 yr old; median age, 57.5 yr) who underwent SCM flap reconstruction from September 2011 to September 2014. All patients underwent surgical resection and immediate reconstruction with the SCM flap. The primary sites included the oral tongue border (n = 10), the base of the tongue (n = 3), the mandibular gingiva (n = 3), the floor of the mouth (n = 2), the buccal mucosa (n = 1), and the anterior neck skin (n = 1). RESULTS: The dimensions of the skin paddle ranged from 5 * 4 to 8 * 5 cm (length * width; mean, 6.7 * 4.2 cm). Arteriovenous type 1A1V of the superior thyroid arteriovenous system accounted for 30% of cases, 1A2V accounted for 30% of cases, 2A2V accounted for 25% of cases, 2A1V accounted for 5% of cases, 2A3V accounted for 5% of cases, and 3A2V accounted for 5% of cases. The mean number was 10.7 lymph nodes (standard deviation, 4.1 lymph nodes) per dissection above level II and 2 cases had level II lymph nodes metastasis. Only 1 case (5%) exhibited marginal loss of the skin paddle. The average operative time was 6.8 +/- 0.9 hours and hospitalization was 12 +/- 2.2 days. Follow-up ranged from 2 to 36 months. Two patients died of metastatic disease and 2 patients developed neck recurrences. CONCLUSIONS: Using the SCM flap with modifications is a reliable and convenient technique with wide application in the reconstruction of head and neck defects. PMID- 26358726 TI - Long-Term Follow-Up of the Repair of the Multiple-Branch Facial Nerve Defect Using Acellular Nerve Allograft. AB - PURPOSE: To assess the clinical efficacy of the repair of facial nerve defects by allograft transplantation using acellular facial nerves. MATERIALS AND METHODS: Seven patients with facial nerve defects, ranging from damage to 1 facial nerve branch to combined defects of all branches, were enrolled. Defects ranged from 3 to longer than 4 cm. All defects were repaired by transplantation of acellular facial nerve allografts. Static and dynamic symmetry and facial expressions were evaluated using the House-Brackmann classification and the functional status of the facial nerve was assessed electromyographically. No patient received immunosuppressive therapy. RESULTS: All wounds healed well, with no swelling or inflammatory exudation. The patients recovered facial nerve function to various extents. Six months postoperatively, 4 of 7 patients showed static facial asymmetry. Twelve months postoperatively, 3 patients had static facial asymmetry with normal eye closure, and only careful observation could detect slight asymmetry of forehead movement. Two of 7 patients showed moderate facial nerve dysfunction. Ipsilateral facial movement and facial asymmetry were obvious in the patient whose defect affected the common trunk and all facial nerve branches. Two years postoperatively, 5 of 7 patients had mild facial nerve dysfunction, with symmetric faces and incomplete eye occlusion. Six years postoperatively, these patients continued to show symmetric faces and incomplete ipsilateral eye occlusion, but facial muscle function was considerably restored. Follow-up electromyography showed neurologic recovery in all patients. CONCLUSION: The repair of a facial nerve defect by transplantation of an acellular facial nerve allograft is feasible. PMID- 26358727 TI - Group and sparse group partial least square approaches applied in genomics context. AB - MOTIVATION: The association between two blocks of 'omics' data brings challenging issues in computational biology due to their size and complexity. Here, we focus on a class of multivariate statistical methods called partial least square (PLS). Sparse version of PLS (sPLS) operates integration of two datasets while simultaneously selecting the contributing variables. However, these methods do not take into account the important structural or group effects due to the relationship between markers among biological pathways. Hence, considering the predefined groups of markers (e.g. genesets), this could improve the relevance and the efficacy of the PLS approach. RESULTS: We propose two PLS extensions called group PLS (gPLS) and sparse gPLS (sgPLS). Our algorithm enables to study the relationship between two different types of omics data (e.g. SNP and gene expression) or between an omics dataset and multivariate phenotypes (e.g. cytokine secretion). We demonstrate the good performance of gPLS and sgPLS compared with the sPLS in the context of grouped data. Then, these methods are compared through an HIV therapeutic vaccine trial. Our approaches provide parsimonious models to reveal the relationship between gene abundance and the immunological response to the vaccine. AVAILABILITY AND IMPLEMENTATION: The approach is implemented in a comprehensive R package called sgPLS available on the CRAN. CONTACT: b.liquet@uq.edu.au SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26358728 TI - SeDuS: segmental duplication simulator. AB - SUMMARY: SeDuS is the first flexible and user-friendly forward-in-time simulator of patterns of molecular evolution within segmental duplications undergoing interlocus gene conversion and crossover. SeDuS introduces known features of interlocus gene conversion such as biased directionality and dependence on local sequence identity. Additionally, it includes aspects such as different selective pressures acting upon copy number and flexible crossover distributions. A graphical user interface allows fast fine-tuning of relevant parameters and straightforward real-time analysis of the evolution of duplicates. AVAILABILITY AND IMPLEMENTATION: SeDuS is implemented in C++ and can be run via command line or through a graphical user interface developed using Qt C++. Source code and binary executables for Linux, OS X and Windows are freely available at www.biologiaevolutiva.org/sedus/. A tutorial with a detailed description of implementation, parameters and output files is available online. CONTACT: arcadi.navarro@upf.edu. PMID- 26358729 TI - Cas-Designer: a web-based tool for choice of CRISPR-Cas9 target sites. AB - We present Cas-Designer, a user-friendly program to aid researchers in choosing appropriate target sites in a gene of interest for type II CRISPR/Cas-derived RNA guided endonucleases, which are now widely used for biomedical research and biotechnology. Cas-Designer rapidly provides the list of all possible guide RNA sequences in a given input DNA sequence and their potential off-target sites including bulge-type sites in a genome of choice. In addition, the program assigns an out-of-frame score to each target site to help users choose appropriate sites for gene knockout. Cas-Designer shows the results in an interactive table and provides user-friendly filter functions. AVAILABILITY AND IMPLEMENTATION: Free access at http://rgenome.net/cas-designer/. PMID- 26358730 TI - Inferred miRNA activity identifies miRNA-mediated regulatory networks underlying multiple cancers. AB - MOTIVATION: MicroRNAs (miRNAs) play a key role in regulating tumor progression and metastasis. Identifying key miRNAs, defined by their functional activities, can provide a deeper understanding of biology of miRNAs in cancer. However, miRNA expression level cannot accurately reflect miRNA activity. RESULTS: We developed a computational approach, ActMiR, for identifying active miRNAs and miRNA mediated regulatory mechanisms. Applying ActMiR to four cancer datasets in The Cancer Genome Atlas (TCGA), we showed that (i) miRNA activity was tumor subtype specific; (ii) genes correlated with inferred miRNA activities were more likely to enrich for miRNA binding motifs; (iii) expression levels of these genes and inferred miRNA activities were more likely to be negatively correlated. For the four cancer types in TCGA we identified 77-229 key miRNAs for each cancer subtype and annotated their biological functions. The miRNA-target pairs, predicted by our ActMiR algorithm but not by correlation of miRNA expression levels, were experimentally validated. The functional activities of key miRNAs were further demonstrated to be associated with clinical outcomes for other cancer types using independent datasets. For ER(-)/HER2(-) breast cancers, we identified activities of key miRNAs let-7d and miR-18a as potential prognostic markers and validated them in two independent ER(-)/HER2(-) breast cancer datasets. Our work provides a novel scheme to facilitate our understanding of miRNA. In summary, inferred activity of key miRNA provided a functional link to its mediated regulatory network, and can be used to robustly predict patient's survival. AVAILABILITY AND IMPLEMENTATION: the software is freely available at http://research.mssm.edu/integrative-network-biology/Software.html. CONTACT: jun.zhu@mssm.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26358731 TI - Splenic gene expression profiling in White Leghorn layer inoculated with the Salmonella enterica serovar Enteritidis. AB - Salmonella enterica serovar Enteritidis (SE) is a foodborne pathogen that can threaten human health through contaminated poultry products. Live poultry, chicken eggs and meat are primary sources of human salmonellosis. To understand the genetic resistance of egg-type chickens in response to SE inoculation, global gene expression in the spleen of 20-week-old White Leghorn was measured using the Agilent 4 * 44 K chicken microarray at 7 and 14 days following SE inoculation (dpi). Results showed that there were 1363 genes significantly differentially expressed between inoculated and non-inoculated groups at 7 dpi (I7/N7), of which 682 were up-regulated and 681 were down-regulated genes. By contrast, 688 differentially expressed genes were observed at 14 dpi (I14/N14), of which 371 were up-regulated genes and 317 were down-regulated genes. There were 33 and 28 immune-related genes significantly differentially expressed in the comparisons of I7/N7 and I14/N14 respectively. Functional annotation revealed that several Gene Ontology (GO) terms related to immunity were significantly enriched between the inoculated and non-inoculated groups at 14 dpi but not at 7 dpi, despite a similar number of immune-related genes identified between I7/N7 and I14/N14. The immune response to SE inoculation changes with different time points following SE inoculation. The complicated interaction between the immune system and metabolism contributes to the immune responses to SE inoculation of egg-type chickens at 14 dpi at the onset of lay. GC, TNFSF8, CD86, CD274, BLB1 and BLB2 play important roles in response to SE inoculation. The results from this study will deepen the current understanding of the genetic response of the egg-type chicken to SE inoculation at the onset of egg laying. PMID- 26358732 TI - Spectral analysis on origination of the bands at 437 nm and 475.5 nm of chlorophyll fluorescence excitation spectrum in Arabidopsis chloroplasts. AB - Chlorophyll fluorescence has been often used as an intrinsic optical molecular probe to study photosynthesis. In this study, the origin of bands at 437 and 475.5 nm in the chlorophyll fluorescence excitation spectrum for emission at 685 nm in Arabidopsis chloroplasts was investigated using various optical analysis methods. The results revealed that this fluorescence excitation spectrum was related to the absorption characteristics of pigment molecules in PSII complexes. Moreover, the excitation band centred at 475.5 nm had a blue shift, but the excitation band at 437 nm changed relatively less due to induction of non photochemical quenching (NPQ). Furthermore, fluorescence emission spectra showed that this blue shift occurred when excitation energy transfer from both chlorophyll b (Chl b) and carotenoids (Cars) to chlorophyll a (Chl a) was blocked. These results demonstrate that the excitation band at 437 nm was mainly contributed by Chl a, while the excitation band at 475.5 nm was mainly contributed by Chl b and Cars. The chlorophyll fluorescence excitation spectrum, therefore, could serve as a useful tool to describe specific characteristics of light absorption and energy transfer between light-harvesting pigments. PMID- 26358734 TI - Copy number variations in the amylase gene (AMY2B) in Japanese native dog breeds. AB - A recent study suggested that increased copy numbers of the AMY2B gene might be a crucial genetic change that occurred during the domestication of dogs. To investigate AMY2B expansion in ancient breeds, which are highly divergent from modern breeds of presumed European origins, we analysed copy numbers in native Japanese dog breeds. Copy numbers in the Akita and Shiba, two ancient breeds in Japan, were higher than those in wolves. However, compared to a group of various modern breeds, Akitas had fewer copy numbers, whereas Shibas exhibited the same level of expansion as modern breeds. Interestingly, average AMY2B copy numbers in the Jomon-Shiba, a unique line of the Shiba that has been bred to maintain their appearance resembling ancestors of native Japanese dogs and that originated in the same region as the Akita, were lower than those in the Shiba. These differences may have arisen from the earlier introduction of rice farming to the region in which the Shiba originated compared to the region in which the Akita and the Jomon-Shiba originated. Thus, our data provide insights into the relationship between the introduction of agriculture and AMY2B expansion in dogs. PMID- 26358733 TI - Changes in Reward after Gastric Bypass: the Advantages and Disadvantages. AB - Gastric bypass surgery is an effective long-term weight loss intervention. Key to its success appears a putative shift in food preference away from high-energy density foods associated with a reduced appetitive drive and loss of neural reactivity in the reward system of the brain towards food. Post-prandial exaggerated satiety gut hormone responses have been implicated as mediators. Whilst the positive impact of bariatric surgery on both physical and psychological outcomes for many patients is clearly evident, a subset of patients appear to be detrimentally affected by this loss of reward from food and by a lack of alternative strategies for regulating affect after surgery. Mindfulness training has emerged as a potential tool in reducing the need for immediate reward that underpins much of eating behaviour. Further research is needed to help identify patients who may be more vulnerable after gastric bypass and which forms of support may be most beneficial. PMID- 26358735 TI - Study on the interaction of beta-carotene and astaxanthin with trypsin and pepsin by spectroscopic techniques. AB - beta-Carotene and astaxanthin are two carotenoids with powerful antioxidant properties, but the binding mechanisms of beta-carotene/astaxanthin to proteases remain unclear. In this study, the interaction of these two carotenoids with trypsin and pepsin was investigated using steady-state and time-resolved fluorescence measurements, synchronous fluorescence spectroscopy, UV-vis absorption spectroscopy and circular dichroism (CD) spectroscopy. The experimental results indicated that the quenching mechanisms of trypsin/pepsin by the two carotenoids are static processes. The binding constants of trypsin and pepsin with these two carotenoids are in the following order: astaxanthin-trypsin > astaxanthin-pepsin > beta-carotene-trypsin > beta-carotene-pepsin, respectively. Thermodynamic investigations revealed that the interaction between the two carotenoids and trypsin/pepsin is synergistically driven by enthalpy and entropy, and hydrophobic forces and electrostatic attraction have a significant role in the reactions. In addition, as shown by synchronous fluorescence spectroscopy, UV-vis absorption spectroscopy and CD, the two carotenoids may induce conformational and microenvironmental changes in trypsin/pepsin. The study provides an accurate and full basic data for clarifying the binding mechanisms of the two carotenoids with trypsin/pepsin and is helpful in understanding their effect on protein function and their biological activity in vivo. PMID- 26358736 TI - Expression profiling of the GBP1 gene as a candidate gene for porcine reproductive and respiratory syndrome resistance. AB - A genomic region in pig chromosome 4 has been previously associated with higher viraemia levels and lower weight gain following porcine reproduction and respiratory syndrome virus (PRRSV) infection. The region includes the marker WUR1000125, a G>A polymorphism next to a putative polyadenylation site in the 3' untranslated region (3'-UTR) of the guanylate-binding protein 1, interferon induced (GBP1) gene. The protein encoded by GBP1 is a negative regulator of T cell responses. We show here that GBP1 expression is lower in liver and tonsils of pigs carrying the WUR1000125-G allele due to differential allele expression (allele A expression is 1.9-fold higher than for allele G). We also show that the GBP1 gene has two active polyadenylation signals 421 bp apart and that polyadenylation usage is dependent on the WUR1000125 genotype. The distal site is the most prevalently used in all samples, but the presence of the A allele favours the generation of shorter transcripts from the proximal site. This is confirmed by a differential allele expression study in AG genotype liver and tonsil samples. The interaction between WUR1000125 and other mutations identified in the 5'- and 3'-UTR regions of this gene needs to be studied. In conclusion, our study indicates that the WUR1000125 mutation is associated with changes in the expression of the negative T-cell regulator GBP1 gene. However, the chromosome 4 locus for PRRSV viraemia levels and weight gain contains a cluster of four other GBP genes that remain to be studied as candidate genes for this QTL. PMID- 26358737 TI - Cation-tunable blue phosphor Ca2PO4Cl:Eu2+: enhancive emission and site occupancy. AB - A series of blue phosphors Ca(1.98-x)M(x)PO4Cl:0.02Eu(2+) (M = Mg and Sr) with different values of x were synthesized using a high-temperature solid-state reaction. X-Ray diffraction and photoluminescence measurements were used to study the phase structure and luminescence properties. Ca2PO4Cl:0.02Eu(2+) exhibits a tunable emission intensity and color due to the incorporation of Sr(2+) or Mg(2+). The incorporation of Sr(2+) reduces the luminescence intensity and results in a slight red shift in the emission band. The incorporation of Mg(2+) results in enhanced emission and a clear blue shift in the emission band along with a tunable chromatic coordination. Under excitation at lambda = 334 nm, the emission intensity of the Mg(2+)-doped Ca2PO4Cl:0.02Eu(2+) is found to be 250% that of Ca2PO4Cl:0.02Eu(2+). The luminescence behaviors of the as-synthesized phosphors are discussed according to the host crystal structure and site occupancy of Eu(2+). The results indicate that Mg(2+)-doped Ca2PO4Cl:Eu(2+) is more applicable as a near-UV-convertible blue phosphor for white light-emitting diodes. PMID- 26358739 TI - Systematic review with meta-analysis: endoscopic balloon dilatation for Crohn's disease strictures. AB - BACKGROUND: Endoscopic balloon dilatation (EBD) is recognised treatment for symptomatic Crohn's strictures. Several case series report its efficacy. A systematic analysis for overall efficacy can inform the design of future studies. AIM: To examine symptomatic (SR) and technical response (TR) and adverse events (AE) of EBD. Stricture characteristics were also explored. METHODS: A systematic search strategy of COCHRANE, MEDLINE and EMBASE was performed. All original studies reporting outcomes of EBD for Crohn's strictures were included. SR was defined as obstructive symptom-free outcome at the end of follow-up, TR as post dilatation passage of the endoscope through a stricture, and adverse event as the presence of complication (perforation and/or bleeding). Pooled event rates across studies were expressed with summative statistics. RESULTS: Twenty-five studies included 1089 patients and 2664 dilatations. Pooled event rates for SR, TR, complications and perforations were 70.2% (95% CI: 60-78.8%), 90.6% (95% CI: 87.8 92.8%), 6.4% (95% CI: 5.0-8.2) and 3% (95% CI: 2.2-4.0%) respectively. Cumulative surgery rate at 5 year follow-up was 75%. Pooled unweighted TR, SR, complication, perforation and surgery rates were 84%, 45%, 15%, 9% and 21% for de novo and 84%, 58%, 22%, 5% and 32% for anastomotic strictures. Outcomes between two stricture types were no different on subgroup meta-analysis. CONCLUSIONS: Efficacy and complication rates for endoscopic balloon dilatation were higher than previously reported. From the few studies with 5 year follow-up the majority required surgery. Future studies are needed to determine whether endoscopic balloon dilatation has significant long-term benefits. PMID- 26358740 TI - Sinus Floor Augmentation Using Straumann(r) BoneCeramicTM and Bio-Oss(r) in a Split Mouth Design and Later Placement of Implants: A 5-Year Report from a Longitudinal Study. AB - BACKGROUND: Straumann(r) BoneCeramicTM is a synthetic biphasic calcium phosphate (BCP) aimed for sinus floor augmentation. Long-term follow-up of implants placed in BCP after sinus augmentation is still missing. PURPOSE: The primary aim of the study was to compare survival rates and marginal bone loss of Straumann SLActive implants placed in either BCP (test) or Bio-Oss(r) (DBB) (control) after sinus floor augmentation. The secondary aim was to calculate graft sinus height at different time points. MATERIALS AND METHODS: Bilateral sinus floor augmentation was performed in a split mouth model. Eleven patients (mean age 67 years) received 100% BCP on one side and 100% DBB on the contralateral side. After 8 months of graft healing, 62 Straumann SLActive implants were placed. After 5 years of functional loading (6 years after augmentation) of implants, marginal bone levels and grafted sinus height were measured, and implant survival and success rates were calculated. RESULTS: After 5 years of loading, all prosthetic constructions were in function although two implants were lost in each grafting material. The overall implant survival rate was 93.5% (91.7% for BCP, 91.3% for DBB, and 100% for residual bone). The success rates were 83.3% and 91.3% for BCP and DBB, respectively. There was no statistically significant difference in mean marginal bone level after 5 years between BCP (1.4 +/- 1.2 mm) and DBB (1.0 +/- 0.7 mm). Graft height reduction (GHR) after 6 years was limited to 6.6% for BCP and 5.8% for DBB. CONCLUSION: In this limited RCT study, the choice of biomaterial used for sinus floor augmentation did not seem to have any impact on survival rates and marginal bone level of the placed implants after 5 years of functional loading and GHR was minimal. PMID- 26358738 TI - Targeting Inflammation Through a Physical Active Lifestyle and Pharmaceuticals for the Treatment of Type 2 Diabetes. AB - Evidence exists that interleukin (IL)-1beta is involved in pancreatic beta-cell damage, whereas TNF-alpha appears to be a key molecule in peripheral insulin resistance. Although increased plasma levels of IL-6 are seen in individuals with type 2 diabetes, mechanistic studies suggest that moderate acute elevations in IL 6, as provoked by exercise, exert anti-inflammatory effects by an inhibition of TNF-alpha and by stimulating IL-1 receptor antagonist (ra), thereby limiting IL 1beta signaling. A number of medical treatments have anti-inflammatory effects. IL-1 antagonists have been tested in clinical studies and appear very promising. Also, there is a potential for anti-TNF-alpha strategies and salsalate has been shown to improve insulin sensitivity in clinical trials. Furthermore, the anti inflammatory potential of statins, antagonists of the renin-angiotensin system, and glucose-lowering agents are discussed. While waiting for the outcome of long term clinical pharmacological trials, it should be emphasized that physical activity represents a natural strong anti-inflammatory intervention with little or no side effects. PMID- 26358741 TI - Site-specific labeling of synthetic peptide using the chemoselective reaction between N-methoxyamino acid and isothiocyanate. AB - Site-specific labeling of synthetic peptides carrying N-methoxyglycine (MeOGly) by isothiocyanate is demonstrated. A nonapeptide having MeOGly at its N-terminus was synthesized by the solid-phase method and reacted with phenylisothiocyanate under various conditions. In acidic solution, the reaction specifically gave a peptide having phenylthiourea structure at its N-terminus, leaving side chain amino group intact. The synthetic human beta-defensin-2 carrying MeOGly at its N terminus or the side chain amino group of Lys(10) reacted with phenylisothiocyanate or fluorescein isothiocyanate also at the N-methoxyamino group under the same conditions, demonstrating that this method is generally useful for the site-specific labeling of linear synthetic peptides as well as disulfide-containing peptides. PMID- 26358742 TI - Facile and selective covalent grafting of an RGD-peptide to electrospun scaffolds improves HUVEC adhesion. AB - The development of a biomimetic surface able to promote endothelialization is fundamental in the search for blood vessel substitutes that prevent the formation of thrombi or hyperplasia. This study aims at investigating the effect of functionalization of poly-epsilon-caprolactone or poly(L-lactic acid-co-E caprolactone) electrospun scaffolds with a photoreactive adhesive peptide. The designed peptide sequence contains four Gly-Arg-Gly-Asp-Ser-Pro motifs per chain and a p-azido-Phe residue at each terminus. Different peptide densities on the scaffold surface were obtained by simply modifying the peptide concentration used in pretreatment of the scaffold before UV irradiation. Scaffolds of poly-epsilon caprolactone embedded with adhesive peptides were produced to assess the importance of peptide covalent grafting. Our results show that the scaffolds functionalized with photoreactive peptides enhance adhesion at 24 h with a dose dependent effect and control the proliferation of human umbilical vein endothelial cells, whereas the inclusion of adhesive peptide in the electrospun matrices by embedding does not give satisfactory results. PMID- 26358745 TI - Relative Ease in Creating Detailed Orthographic Representations Contrasted with Severe Difficulties to Maintain Them in Long-term Memory Among Dyslexic Children. AB - Most research into orthographic learning abilities has been conducted in English with typically developing children using reading-based tasks. In the present study, we examined the abilities of French-speaking children with dyslexia to create novel orthographic representations for subsequent use in spelling and to maintain them in long-term memory. Their performance was compared with that of chronological age (CA)-matched and reading age (RA)-matched control children. We used an experimental task designed to provide optimal learning conditions (i.e. 10 spelling practice trials) ensuring the short-term acquisition of the spelling of the target orthographic word forms. After a 1-week delay, the long-term retention of the targets was assessed by a spelling post-test. Analysis of the results revealed that, in the short term, children with dyslexia learned the novel orthographic word forms well, only differing from both CA and RA controls on the initial decoding of the targets and from CA controls on the first two practice trials. In contrast, a dramatic drop was observed in their long-term retention relative to CA and RA controls. These results support the suggestion of the self-teaching hypothesis (Share, 1995) that initial errors in the decoding and spelling of unfamiliar words may hinder the establishment of fully specified novel orthographic representations. PMID- 26358743 TI - T cell receptor signaling pathway is overexpressed in CD4(+) T cells from HAM/TSP individuals. AB - Human T-lymphotropic virus type 1 (HTLV-1) is a human retrovirus related to the chronic neuroinflammatory disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). CD4(+) T cells activation appears to play a key role on HTLV-1 infection. Here we investigated the expression of genes associated to T cell activation CD3e molecule, epsilon (CD3E), lymphocyte-specific protein tyrosine kinase (LCK), vav 1 guanine nucleotide exchange factor (VAV1), and zeta chain (TCR) associated protein kinase 70kDa (ZAP70) on T lymphocytes of HTLV-1 infected individuals and compared to healthy uninfected individuals (CT). We observed that CD3E, LCK, ZAP70, and VAV1 gene expression were increased in CD4(+) T cells from HAM/TSP group compared to HTLV-1 asymptomatic patients (HAC). Moreover, ZAP70 and VAV1 were also upregulated in HAM/TSP compared to CT group. We detected a positive correlation among all these genes. We also observed that CD3E, LCK, and VAV1 genes had a positive correlation with the proviral load (PVL) and Tax expression. These results suggest that PVL and Tax protein could drive CD3E, LCK, and VAV1 gene expression in CD4(+) T cells, and these genes function on a synchronized way on the CD4(+) T cell activation. The elucidation of the mechanisms underlying T cell receptor signaling pathway is of considerable interest and might lead to new insights into the mechanism of HAM/TSP. PMID- 26358744 TI - Challenging Mycobacterium tuberculosis dormancy mechanisms and their immunodiagnostic potential. AB - Mycobacterium tuberculosis is the etiologic agent of tuberculosis, one of the world's greatest cause of morbidity and mortality due to infectious disease. Many evolutionary mechanisms have contributed to its high level of adaptation as a host pathogen. Prior to become dormant, a group of about 50 genes related to metabolic changes are transcribed by the DosR regulon, one of the most complex and important systems of host-pathogen interaction. This genetic mechanism allows the mycobacteria to persist during long time periods, establishing the so-called latent infection. Even in the presence of a competent immune response, the host cannot eliminate the pathogen, only managing to keep it surrounded by an unfavorable microenvironment for its growth. However, conditions such as immunosuppression may reestablish optimal conditions for bacterial growth, culminating in the onset of active disease. The interactions between the pathogen and its host are still not completely elucidated. Nonetheless, many studies are being carried out in order to clarify this complex relationship, thus creating new possibilities for patient approach and laboratory screening. PMID- 26358746 TI - A novel objective method for deceased donor and recipient size matching in liver transplantation. AB - Although the consequences of implantation of a large whole liver graft into a small recipient such as compression and compromise of graft perfusion are well known, no accepted measure to aid in donor-to-recipient size matching exists. Donor liver graft and recipient native liver weights as well as donor and recipient size and amount of ascites were investigated in 1953 patients who underwent liver transplantation using deceased donor grafts between January 2002 and July 2013. We used a previously described formula for liver resections (standardized total liver volume [sTLV] = -794.41 + 1267.28 * body surface area [m(2)]) for calculating sTLV, in the current cohort of deceased liver donors. Early allograft dysfunction (EAD) and graft survival were the primary outcome measures. The formula for calculating sTLV for liver resections was validated as an accurate predictor of liver volume in the current cohort of deceased liver donors (r(2) = 0.45; P < 0.001). A cutoff point of sTLV ratio >= 1.25 was determined through receiver operating characteristic curves, and patients were dichotomized into 2 groups. In the sTLV ratio >= 1.25 group, 50% of patients developed EAD compared to 25% of patients in the sTLV ratio < 1.25 group (P < 0.001). The proportion of patients developing graft failure within 90 days was 9.6% in the sTLV ratio >= 1.25 group and 5.4% in the sTLV ratio < 1.25 group (P = 0.045). This study validates the use of the sTLV for prediction of actual donor liver weight in the transplant setting. Using this formula, donors with a calculated sTLV size ratio >= 1.25 have an increased risk of EAD and therefore caution should be used when that value is exceeded. This adjusted size ratio can be used as a decision aid when considering donor and recipient matching with potential liver organ offers. PMID- 26358747 TI - Role of peripheral sigma-1 receptors in ischaemic pain: Potential interactions with ASIC and P2X receptors. AB - BACKGROUND: The role of peripheral sigma-1 receptors (Sig-1Rs) in normal nociception and in pathologically induced pain conditions has not been thoroughly investigated. Since there is mounting evidence that Sig-1Rs modulate ischaemia induced pathological conditions, we investigated the role of Sig-1Rs in ischaemia induced mechanical allodynia (MA) and addressed their possible interaction with acid-sensing ion channels (ASICs) and P2X receptors at the ischaemic site. METHODS: We used a rodent model of hindlimb thrombus-induced ischaemic pain (TIIP) to investigate their role. Western blot was performed to observe changes in Sig-1R expression in peripheral nervous tissues. MA was measured after intraplantar (i.pl.) injections of antagonists for the Sig-1, ASIC and P2X receptors in TIIP rats or agonists of each receptor in naive rats. RESULTS: Sig 1R expression significantly increased in skin, sciatic nerve and dorsal root ganglia at 3 days post-TIIP surgery. I.pl. injections of the Sig-1R antagonist, BD-1047 on post-operative days 0-3 significantly attenuated the development of MA during the induction phase, but had no effect on MA when given during the maintenance phase (days 3-6 post-surgery). BD-1047 synergistically increased amiloride (an ASICs blocker)- and TNP-ATP (a P2X antagonist)-induced analgesic effects in TIIP rats. In naive rats, i.pl. injection of Sig-1R agonist PRE-084 alone did not produce MA; but it did induce MA when co-administered with either an acidic pH solution or a sub-effective dose of alphabetameATP. CONCLUSION: Peripheral Sig-1Rs contribute to the induction of ischaemia-induced MA via facilitation of ASICs and P2X receptors. Thus, peripheral Sig-1Rs represent a novel therapeutic target for the treatment of ischaemic pain. PMID- 26358748 TI - Conflict Minerals in Electronic Systems: An Overview and Critique of Legal Initiatives. AB - The Democratic Republic of Congo has vast natural resources, many of which are regularly exploited by the electronics industry. Unfortunately, in addition to these resources, there are widespread human rights abuses committed by armed groups entrenched in the eastern part of the Democratic Republic of Congo. These armed groups are using profits from these minerals as a source of funding. Their human rights abuses have led to a growing humanitarian interest in the region and prompted the international community to action. This paper explores the conflicts in the Democratic Republic of Congo, provides an understanding of the link between human rights abuses and conflict minerals, and interprets and critiques the legal actions of the international community. PMID- 26358749 TI - Darurah (Necessity) and Its Application in Islamic Ethical Assessment of Medical Applications: A Review on Malaysian Fatwa. AB - The discovery and invention of new medical applications may be considered blessings to humankind. However, some applications which might be the only remedy for certain diseases may contain ingredients or involve methods that are not in harmony with certain cultural and religious perspectives. These situations have raised important questions in medical ethics; are these applications completely prohibited according to these perspectives, and is there any room for mitigation? This paper explores the concept of darurah (necessity) and its deliberation in the formulation of fatwas on medicine issued by the National Fatwa Council of Malaysia. Darurah has explicitly been taken into consideration in the formulation of 14 out of 45 fatwas on medicine thus far, including one of the latest fatwas regarding uterine donation and transplantation. These fatwas are not only limited to the issues regarding the use of unlawful things as remedies. They include issues pertaining to organ transplantation, management of the corpse and treatment of brain dead patients. While deliberation of darurah in medicine may vary from issue to issue, darurah applies in a dire situation in which there are no lawful means to prevent harm that may be inflicted upon human life. Nevertheless, other aspects must also be taken into the deliberation. For example, consent must be obtained from the donor or his next of kin (after his death) to conduct a cadaveric organ transplantation. PMID- 26358750 TI - HMDB and 5-AzadC Combination Reverses Tumor Suppressor CCAAT/Enhancer-Binding Protein Delta to Strengthen the Death of Liver Cancer Cells. AB - Hepatocellular carcinoma (HCC) can arise from chronic inflammation due to viral infection, organ damage, drug toxicity, or alcohol abuse. Moreover, gene desensitization via aberrant CpG island methylation is a frequent epigenetic defect in HCC. However, the details of how inflammation is linked with epigenetic mediated desensitization of tumor suppressor genes remains less investigated. In this study, we found that loss of CEBPD enhances the growth of liver cancer cells and is associated with the occurrence of liver cancers, as determined by the assessment of clinical specimens and in vivo animal models. Moreover, E2F1 regulated epigenetic axis attenuated CEBPD expression in liver cancer cells. CEBPD is responsive to the hydroxymethyldibenzoylmethane (HMDB)-induced p38/CREB pathway and plays an important role in the HMDB-induced apoptosis of cancer cells. Regarding depression of epigenetic effects to enhance HMDB-induced CEBPD expression, the combination of HMDB and 5-Aza-2'-deoxycytidine (5-AzadC) could enhance the death of liver cancer cells and reduce the tumor formation of Huh7 xenograft mice. In conclusion, these results suggest that CEBPD could be a useful diagnostic marker and therapeutic target in HCC. The results also reveal the therapeutic potential for low-dose 5-AzadC to enhance the HMDB-induced death of HCC cells. PMID- 26358751 TI - AZD2014, an Inhibitor of mTORC1 and mTORC2, Is Highly Effective in ER+ Breast Cancer When Administered Using Intermittent or Continuous Schedules. AB - mTOR is an atypical serine threonine kinase involved in regulating major cellular functions, such as nutrients sensing, growth, and proliferation. mTOR is part of the multiprotein complexes mTORC1 and mTORC2, which have been shown to play critical yet functionally distinct roles in the regulation of cellular processes. Current clinical mTOR inhibitors only inhibit the mTORC1 complex and are derivatives of the macrolide rapamycin (rapalogs). Encouraging effects have been observed with rapalogs in estrogen receptor-positive (ER(+)) breast cancer patients in combination with endocrine therapy, such as aromatase inhibitors. AZD2014 is a small-molecule ATP competitive inhibitor of mTOR that inhibits both mTORC1 and mTORC2 complexes and has a greater inhibitory function against mTORC1 than the clinically approved rapalogs. Here, we demonstrate that AZD2014 has broad antiproliferative effects across multiple cell lines, including ER(+) breast models with acquired resistance to hormonal therapy and cell lines with acquired resistance to rapalogs. In vivo, AZD2014 induces dose-dependent tumor growth inhibition in several xenograft and primary explant models. The antitumor activity of AZD2014 is associated with modulation of both mTORC1 and mTORC2 substrates, consistent with its mechanism of action. In combination with fulvestrant, AZD2014 induces tumor regressions when dosed continuously or using intermittent dosing schedules. The ability to dose AZD2014 intermittently, together with its ability to block signaling from both mTORC1 and mTORC2 complexes, makes this compound an ideal candidate for combining with endocrine therapies in the clinic. AZD2014 is currently in phase II clinical trials. PMID- 26358752 TI - Identification of Novel Ezrin Inhibitors Targeting Metastatic Osteosarcoma by Screening Open Access Malaria Box. AB - Ezrin is a member of the ERM (ezrin, radixin, moesin) family of proteins and functions as a linker between the plasma membrane and the actin cytoskeleton. Ezrin is a key driver of tumor progression and metastatic spread of osteosarcoma. We discovered a quinoline-based small molecule, NSC305787, that directly binds to ezrin and inhibits its functions in promoting invasive phenotype. NSC305787 possesses a very close structural similarity to commonly used quinoline containing antimalarial drugs. On the basis of this similarity and of recent findings that ezrin has a likely role in the pathogenesis of malaria infection, we screened antimalarial compounds in an attempt to identify novel ezrin inhibitors with better efficacy and drug properties. Screening of Medicines for Malaria Venture (MMV) Malaria Box compounds for their ability to bind to recombinant ezrin protein yielded 12 primary hits with high selective binding activity. The specificity of the hits on ezrin function was confirmed by inhibition of the ezrin-mediated cell motility of osteosarcoma cells. Compounds were further tested for phenocopying the morphologic defects associated with ezrin suppression in zebrafish embryos as well as for inhibiting the lung metastasis of high ezrin-expressing osteosarcoma cells. The compound MMV667492 exhibited potent anti-ezrin activity in all biologic assays and had better physicochemical properties for drug-likeness than NSC305787. The drug-like compounds MMV020549 and MMV666069 also showed promising activities in functional assays. Thus, our study suggests further evaluation of antimalarial compounds as a novel class of antimetastatic agents for the treatment of metastatic osteosarcoma. PMID- 26358755 TI - Reversal of alcohol-induced effects on response control due to changes in proprioceptive information processing. AB - Recent research has drawn interest to the effects of binge drinking on response selection. However, choosing an appropriate response is a complex endeavor that usually requires us to process and integrate several streams of information. One of them is proprioceptive information about the position of limbs. As to now, it has however remained elusive how binge drinking affects the processing of proprioceptive information during response selection and control in healthy individuals. We investigated this question using neurophysiological (EEG) techniques in a response selection task, where we manipulated proprioceptive information. The results show a reversal of alcohol-induced effects on response control due to changes in proprioceptive information processing. The most likely explanation for this finding is that proprioceptive information does not seem to be properly integrated in response selection processes during acute alcohol intoxication as found in binge drinking. The neurophysiological data suggest that processes related to the preparation and execution of the motor response, but not upstream processes related to conflict monitoring and spatial attentional orienting, underlie these binge drinking-dependent modulations. Taken together, the results show that even high doses of alcohol have very specific effects within the cascade of neurophysiological processes underlying response control and the integration of proprioceptive information during this process. PMID- 26358754 TI - Early-onset encephalopathy with epilepsy associated with a novel splice site mutation in SMC1A. AB - We report on the clinical and molecular characterization of a female patient with early-onset epileptic encephalopathy, who was found to carry a de novo novel splice site mutation in SMC1A. This girl shared some morphologic and anthropometric traits described in patients with clinical diagnosis of Cornelia de Lange syndrome and with SMC1A mutation but also has severe encephalopathy with early-onset epilepsy. In addition, she had midline hand stereotypies and scoliosis leading to the misdiagnosis of a Rett overlap syndrome. Molecular studies found a novel de novo splice site mutation (c.1911 + 1G > T) in SMC1A. This novel splice mutation was associated with an aberrantly processed mRNA that included intron 11 of the gene. Moreover, quantitative approach by RT-PCR showed a severe reduction of the SMC1A transcript suggesting that this aberrant transcript may be unstable and degraded. Taken together, our data suggest that the phenotype may be due to a loss-of-function of SMC1A in this patient. Our findings suggest that loss-of-function mutations of SMC1A may be associated with early-onset encephalopathy with epilepsy. PMID- 26358753 TI - Neutralization of KIT Oncogenic Signaling in Leukemia with Antibodies Targeting KIT Membrane Proximal Domain 5. AB - KIT is a cell surface tyrosine kinase receptor whose ligand stem cell factor (SCF) triggers homodimerization and activation of downstream effector pathways involved in cell survival, proliferation, homing, or differentiation. KIT activating mutations are major oncogenic drivers in subsets of acute myeloid leukemia (AML), in mast cell leukemia, and in gastrointestinal stromal tumors (GIST). The overexpression of SCF and/or wild-type (WT) KIT is also observed in a number of cancers, including 50% of AML and small cell lung cancer. The use of tyrosine kinase inhibitors (TKI) in these pathologies is, however, hampered by initial or acquired resistance following treatment. Using antibody phage display, we obtained two antibodies (2D1 and 3G1) specific for the most membrane proximal extracellular immunoglobulin domain (D5) of KIT, which is implicated in KIT homodimerization. Produced as single chain variable antibody fragments fused to the Fc fragment of a human IgG1, bivalent 2D1-Fc and 3G1-Fc inhibited KIT dependent growth of leukemic cell lines expressing WT KIT (UT7/Epo) or constitutively active KIT mutants, including the TKI imatinib-resistant KIT D816V mutant (HMC1.2 cell line). In all models, either expressing WT KIT or mutated KIT, 2D1 and 3G1-Fc induced KIT internalization and sustained surface downregulation. However, interestingly, KIT degradation was only observed in leukemic cell lines with oncogenic KIT, a property likely to limit the toxicity of these antibodies in patients. These fully human antibody formats may represent therapeutic tools to target KIT signaling in leukemia or GIST, and to bypass TKI resistance of certain KIT mutants. PMID- 26358756 TI - Severe congenital neutropenia with neurological impairment due to a homozygous VPS45 p.E238K mutation: A case report suggesting a genotype-phenotype correlation. AB - VPS45 mutations cause severe congenital neutropenia (SCN). We report on a girl with SCN and neurological impairment harboring a homozygous p.E238K mutation in VPS45 (vacuolar sorting protein 45). She successfully underwent hematopoietic stem cell transplantation. Our findings delineate the phenotype and indicate a possible genotype-phenotype correlation for neurological involvement. PMID- 26358757 TI - CORR Insights((r)): oxidized zirconium head on crosslinked polyethylene liner in total hip arthroplasty: a 7- to 12-year in vivo comparative wear study. PMID- 26358758 TI - Evidence-based medicine meets person-centred care: a collaborative perspective on the relationship. AB - In a recent list-serve, the way forward for evidence-based medicine was discussed. The purpose of this paper was to share the reflections and multiple perspectives discussed in this peer-to-peer encounter and to invite the reader to think with a mind for positive change in the practice of health care. Let us begin with a simple question. What if we dared to look at evidence-based medicine (EBM) and informed shared decision making like two wheels on a bike? They both need to be full of substance, well connected, lubricated and working in balance, propelled and guided by a competent driver, with good vision to get the bike where we want it to go. We need all the tools in the toolkit for the bike to stay operational and to meet the needs of the driver. By the same rationale, evidence alone is necessary but not sufficient for decision making; values are necessary and if neglected, may default to feelings based on social pressures and peer influence. Medical decisions, even shared ones, lack focus without evidence and application. Just as a bike may need a tune up from time to time to maintain optimal performance, EBM may benefit from a tune up where we challenge ourselves to move away from general assumptions and traditions and instead think clearly about the issues we face and how to ask well-formed, specific questions to get the answers to meet the needs we face in health care. PMID- 26358759 TI - Bioinformatics approaches to single-cell analysis in developmental biology. AB - Individual cells within the same population show various degrees of heterogeneity, which may be better handled with single-cell analysis to address biological and clinical questions. Single-cell analysis is especially important in developmental biology as subtle spatial and temporal differences in cells have significant associations with cell fate decisions during differentiation and with the description of a particular state of a cell exhibiting an aberrant phenotype. Biotechnological advances, especially in the area of microfluidics, have led to a robust, massively parallel and multi-dimensional capturing, sorting, and lysis of single-cells and amplification of related macromolecules, which have enabled the use of imaging and omics techniques on single cells. There have been improvements in computational single-cell image analysis in developmental biology regarding feature extraction, segmentation, image enhancement and machine learning, handling limitations of optical resolution to gain new perspectives from the raw microscopy images. Omics approaches, such as transcriptomics, genomics and epigenomics, targeting gene and small RNA expression, single nucleotide and structural variations and methylation and histone modifications, rely heavily on high-throughput sequencing technologies. Although there are well-established bioinformatics methods for analysis of sequence data, there are limited bioinformatics approaches which address experimental design, sample size considerations, amplification bias, normalization, differential expression, coverage, clustering and classification issues, specifically applied at the single-cell level. In this review, we summarize biological and technological advancements, discuss challenges faced in the aforementioned data acquisition and analysis issues and present future prospects for application of single-cell analyses to developmental biology. PMID- 26358760 TI - Caring for Adults with Intellectual Disability: The Perspectives of Family Carers in South Africa. AB - BACKGROUND: Internationally adults with intellectual disability are largely cared for by their families, especially in low- to middle-income countries (LAMIC). Compared to high-income countries, little is known about their experiences in LAMIC such as South Africa. METHODS: Focus group discussions were carried out with 37 family caregivers (FCGs) in the Cape Town metropole. These were transcribed and analysed thematically. Core categories were identified and validated through member checking. RESULTS: Family caregivers showed strong commitment to care despite the heavy responsibility and burden of care that women especially experience. They recognize the limited personal growth opportunities for people with intellectual disability that increases the caregiving burden. FCGs identify supports and resources in the community that assist them with their care responsibilities but often feel let down by services. CONCLUSIONS: Improved family supports appropriate to the resources in LAMIC are needed especially when existing carers are no longer able to provide care. PMID- 26358761 TI - Characterization of a novel xylanase gene from rumen content of Hu sheep. AB - A novel xylanase gene, xyn-lxy, was cloned from a metagenomic fosmid library, which was previously constructed from the rumen contents of Hu sheep and was functionally characterized in Escherichia coli. The open reading frame was composed of 1923 bp and encoded for 640 amino acids, including a catalytic domain of glycosyl hydrolase family 10 and carbohydrate-binding module 9. The gene showed 97 % identity with uncultured bacterium Contig1552 but low similarity with xylanases from known cellulolytic-degrading microorganisms in the rumen. The recombinant XYN-LXY showed a specific activity of 664.7 U mg(-1). The optimal temperature and pH of the enzyme were 50 degrees C and 6.0, respectively. Specifically, XYN-LXY was exclusively activated by Mn(2+) among all of the cations and reducing agents tested in this study. An enzymatic hydrolysis assay revealed that XYN-LXY degraded birchwood xylan into xylooligosaccharide with a low degree of polymerization. After incubation for 4 h, the concentration of the dominant product, xylobiose, was 2.297 +/- 0.175 mg ml(-1) (74.07 % of total product) followed by xylose with a concentration of 0.656 +/- 0.010 mg ml(-1) (21.14 % of total product). The XYN-LXY exhibited deep degradation effects on the xylan substrate, which were rarely observed with endo-xylanase, making it a promising candidate for industrial application, especially in biofuel production. PMID- 26358763 TI - Mechanism of Modification, by Lidocaine, of Fast and Slow Recovery from Inactivation of Voltage-Gated Na+ Channels. AB - The clinically important suppression of high-frequency discharges of excitable cells by local anesthetics (LA) is largely determined by drug-induced prolongation of the time course of repriming (recovery from inactivation) of voltage-gated Na(+) channels. This prolongation may result from periodic drug binding to a high-affinity binding site during the action potentials and subsequent slow dissociation from the site between action potentials ("dissociation hypothesis"). For many drugs it has been suggested that the fast inactivated state represents the high-affinity binding state. Alternatively, LAs may bind with high affinity to a native slow-inactivated state, thereby accelerating the development of this state during action potentials ("stabilization hypothesis"). In this case, slow recovery between action potentials occurs from enhanced native slow inactivation. To test these two hypotheses we produced serial cysteine mutations of domain IV segment 6 in rNav1.4 that resulted in constructs with varying propensities to enter fast- and slow-inactivated states. We tested the effect of the LA lidocaine on the time course of recovery from short and long depolarizing prepulses, which, under drug free conditions, recruited mainly fast- and slow-inactivated states, respectively. Among the tested constructs the mutation-induced changes in native slow recovery induced by long depolarizations were not correlated with the respective lidocaine-induced slow recovery after short depolarizations. On the other hand, for long depolarizations the mutation-induced alterations in native slow recovery were significantly correlated with the kinetics of lidocaine induced slow recovery. These results favor the "dissociation hypothesis" for short depolarizations but the "stabilization hypothesis" for long depolarizations. PMID- 26358764 TI - Monochromatic excimer light versus combination of topical steroid with vitamin D3 analogue in the treatment of nonsegmental vitiligo: a randomized blinded comparative study. AB - Vitiligo is a difficult disease to treat, socially stigmatizing its patients. Monochromatic excimer light (MEL) was developed for use in dermatology and adapted for the treatment of vitiligo. Comparing the efficacy of MEL versus topical combination therapy of vitamin D3 analogue and steroid in the treatment of nonsegmental vitiligo. Forty-four patients with localized and stable nonsegmental vitiligo participated in the present study. In each patient, two lesions were selected and divided randomly into two groups, group A was treated with daily topical combination of calcipotriol and betamethasone and group B was treated with biweekly sessions of MEL for 3 months. Efficacy based on repigmentation percentages were blindly evaluated by two independent physicians and patient's satisfaction. There was significant improvement in both treatment modalities at the end of the study, but without significant differences in both groups. There was a significant difference between both groups regarding the onset of repigmentation (p-value < 0.05), whereas group B showed early sign of repigmentation in first 4 weeks of treatment in 16 patients versus 7 patients in group A. Both treatment modalities offered encouraging results and both are promising lines for the treatment of vitiligo. PMID- 26358765 TI - Drifting of teeth in the mandible studied in adult human autopsy material. AB - OBJECTIVES: Increase in lower anterior crowding is a general problem among adult Caucasians. The tooth movement responsible for this phenomenon, however, is not fully elucidated. Aim of this study was to describe signs of ongoing tooth movement reflected in the thickness of the bundle bone around mandibular teeth and the distribution of eroding surfaces of the alveolar wall in human autopsy material. MATERIAL AND METHODS: The distribution of bundle bone and eroding surfaces was assessed histomorphometrically on 106 mandibular teeth, and the surrounding bone obtained at autopsy from 35 deceased persons ranging from 19 to 55 years of age. By examining the mesio-distal and bucco-lingual aspects at the cervical and apical levels of the roots, a pattern of tooth movements could be established. RESULTS: The distribution of the bundle bone thickness and the vectors of eroding surfaces enabled the direction of tooth movement to be reconstructed. Mesial and lingual displacement was prevalent for the anterior teeth. CONCLUSION: The signs of ongoing displacement of lower teeth support the concept of crowding occurring in adult individuals and support the maintenance of retainers, even following cessation of growth. PMID- 26358766 TI - Effects of Methyl Mercury Chloride on Rat Hippocampus Structure. AB - The objective of this study is to investigate the impacts of Methyl Mercury Chloride (MMC) on cognitive functions and ultrastructural changes of hippocampus in Sprague Dawley (SD) rats. Thirty healthy 20-day-old male SD rats weighing 30 40 g were randomly divided into three groups to receive daily injections. Two different dose levels were used: 4 mg/kg as high dose (H-MMC) and 2 mg/kg as low dose (L-MMC).The control group received 4 mg/kg saline solution (N-NaCl). After daily subcutaneous injection for 50 days, 6-day Morris water maze tests were used to assess the learning and memory functions of the rats. After a 5-day continuous training, spatial probe tests were conducted of times and paths crossing to the target quadrant on the 6th day. After the rats were euthanized, their hippocampus sections were stained with hematoxylin and eosin and analyzed under bothoptical microscope and electron microscope. The time H-MMC group spent in finding platform was significantly longer as compared toN-NaCl group on day 2 to day 5 and L-MMC group on day 4 to day 5. The number of crossing times of H-MMC group to the target quadrant was 0.63 +/- 0.74, which is much lower than C-NaCl group (3.13 +/- 1.56) with P value <0.05. No statistically significant difference in crossing times was found between L-MMC and C-NaCl groups. For H-MMC group, decreasing number of neurons and disorganized nerve cells were examined under light microscope. Swelling and dissolution of Golgi complex were examined under electron microscope, along with endoplasmic reticulum expansion and cytoplasmic edema. Mild cytoplasmic edema was found in L-MMC group. MMC can cause cognitive impairment in terms of learning and memory in SD rats. Additionally, it can also cause changes in the ultrastructure of neurons and morphological changes in the hippocampus, causing significant damage. PMID- 26358767 TI - Role of Magnesium Transporter Subtype 1 (MagT1) in the Osteogenic Differentiation of Rat Bone Marrow Stem Cells. AB - In the present study, we investigated the role of magnesium transporter subtype 1 (MagT1), a selective Mg transporter protein, in the osteogenic differentiation of rat bone marrow stem cells (rBMSCs). Osteogenic differentiation was monitored by the expressions of alkaline phosphatase (ALP), osteocalcin (OCN), collagen-1 (COL 1) and runt-related transcription factor 2 (RUNX2), and extracellular matrix mineralization of rBMSCs. The expression of MagT1 increased with osteogenic differentiation of rBMSCs, suggesting the importance of intracellular Mg homeostasis to cell differentiation. Alteration of intracellular Mg homeostasis by culture condition with low extracellular Mg significantly reduced the osteogenic differentiation markers ALP, OCN, COL-1, and RUNX2 gene expressions. MagT1 knockdown during the differentiation period also reduced osteogenic differentiation and the extent of matrix mineralization of rBMSCs. In conclusion, our results indicate that Mg and MagT1 play an important role in osteogenic differentiation of rBMSCs and may be involved in the bone regeneration. PMID- 26358762 TI - Is heart rate a risk marker in patients with chronic heart failure and concomitant atrial fibrillation? Results from the MAGGIC meta-analysis. AB - AIM: To investigate the relationship between heart rate and survival in patients with heart failure (HF) and coexisting atrial fibrillation (AF). METHODS AND RESULTS: Patients with AF included in the Meta-analysis Global Group in Chronic Heart Failure (MAGGIC) meta-analysis were the main focus of this analysis (3259 patients from 17 studies). The outcome was all-cause mortality at 3 years. Heart rate was analysed as a categorical (tertiles; T1 <=77 b.p.m., T2 78-98 b.p.m., T3 >=98 b.p.m.) and continuous variable. Cox proportional hazard models were used to compare the risk of all-cause death between tertiles of baseline heart rate. Patients in the highest tertile were more often female, less likely to have an ischaemic aetiology or diabetes, had a lower ejection fraction but higher blood pressure and New York Heart Association (NYHA) class. Higher heart rate was associated with higher mortality in patients with sinus rhythm (SR) but not in those in AF. In patients with heart failure and reduced ejection fraction (HF REF) and AF, death rates per 100 patient years were lowest in the highest heart rate tertile (T1 18.9 vs. T3 15.9) but this difference was not statistically significant (P = 0.10). In patients with heart failure and preserved ejection fraction (HF-PEF), death rates per 100 patient years were highest in the highest heart rate tertile (T1 14.6 vs. T3 16.0, P = 0.014). However, after adjustment for other important prognostic variables, higher heart rate was no longer associated with higher mortality in HF-PEF (or HF-REF). CONCLUSIONS: In this meta analysis of patients with HF, heart rate does not have the same prognostic significance in patients in AF as it does in those in SR, irrespective of ejection fraction or treatment with beta-blocker. PMID- 26358768 TI - Detectable Blood Lead Level and Body Size in Early Childhood. AB - Rates of childhood obesity have risen at the same time rates of high blood lead levels (BLLs) have fallen. Recent studies suggest that higher BLL is inversely associated with body size in older children (ages 3-19 years). No contemporaneous studies have examined if having a detectable BLL is associated with body size in very early childhood. We examined if detectable BLL is associated with body size in early childhood. A total of 299 birth cohort participants completed a study visit at ages 2-3 years with weight and height measurements; prior to this clinic visit, a BLL was drawn as part of routine clinical care. Body mass index (BMI) percentile and Z-score were calculated; children with BMI >=85th percentile were considered overweight/obese at age of 2 years. Detectable BLL was defined as BLL >=1 MUg/dL. A total of 131 (43.8 %) children had a detectable BLL measured at mean aged 15.4 +/- 5.5 months. Mean age at body size assessment was 2.2 +/- 0.3 years (53.2 % male, 68.6 % African-American). After adjusting for race, sex, and birth weight, children with a detectable BLL had a 43 % lower risk of BMI >=85th percentile (P = 0.041) and a 0.35-unit lower BMI Z-score (P = 0.008) compared to children without a detectable BLL. Neither race nor sex modified this association (all interactions P > 0.21). Consistent with recent studies in older children, having a detectable BLL was associated with smaller body size at ages 2-3 years. Additional research on the mechanism of this association is needed but may include mechanisms of appetite suppression via lead. PMID- 26358770 TI - Mitochondrial ATP synthase activity is impaired by suppressed O-GlcNAcylation in Alzheimer's disease. AB - Glycosylation with O-linked beta-N-acetylglucosamine (O-GlcNAc) is one of the protein glycosylations affecting various intracellular events. However, the role of O-GlcNAcylation in neurodegenerative diseases such as Alzheimer's disease (AD) is poorly understood. Mitochondrial adenosine 5'-triphosphate (ATP) synthase is a multiprotein complex that synthesizes ATP from ADP and Pi. Here, we found that ATP synthase subunit alpha (ATP5A) was O-GlcNAcylated at Thr432 and ATP5A O GlcNAcylation was decreased in the brains of AD patients and transgenic mouse model, as well as Abeta-treated cells. Indeed, Abeta bound to ATP synthase directly and reduced the O-GlcNAcylation of ATP5A by inhibition of direct interaction between ATP5A and mitochondrial O-GlcNAc transferase, resulting in decreased ATP production and ATPase activity. Furthermore, treatment of O GlcNAcase inhibitor rescued the Abeta-induced impairment in ATP production and ATPase activity. These results indicate that Abeta-mediated reduction of ATP synthase activity in AD pathology results from direct binding between Abeta and ATP synthase and inhibition of O-GlcNAcylation of Thr432 residue on ATP5A. PMID- 26358769 TI - Rhodium(III)-Catalyzed Allylic C(sp(3))-H Activation of Alkenyl Sulfonamides: Unexpected Formation of Azabicycles. AB - Unsaturated N-sulfonamides undergo a Rh(III)-catalyzed allylic C(sp(3))-H activation followed by insertion with an exogenous internal alkyne. The reaction generates [3.3.0], [4.3.0], and [5.3.0] azabicyclic structures with excellent diastereoselectivity. Deuterium labeling experiments implicate a 1,3-Rh shift as a key step in the mechanism. PMID- 26358771 TI - Human recombinant arginase enzyme reduces plasma arginine in mouse models of arginase deficiency. AB - Arginase deficiency is caused by deficiency of arginase 1 (ARG1), a urea cycle enzyme that converts arginine to ornithine. Clinical features of arginase deficiency include elevated plasma arginine levels, spastic diplegia, intellectual disability, seizures and growth deficiency. Unlike other urea cycle disorders, recurrent hyperammonemia is typically less severe in this disorder. Normalization of plasma arginine levels is the consensus treatment goal, because elevations of arginine and its metabolites are suspected to contribute to the neurologic features. Using data from patients enrolled in a natural history study conducted by the Urea Cycle Disorders Consortium, we found that 97% of plasma arginine levels in subjects with arginase deficiency were above the normal range despite conventional treatment. Recently, arginine-degrading enzymes have been used to deplete arginine as a therapeutic strategy in cancer. We tested whether one of these enzymes, a pegylated human recombinant arginase 1 (AEB1102), reduces plasma arginine in murine models of arginase deficiency. In neonatal and adult mice with arginase deficiency, AEB1102 reduced the plasma arginine after single and repeated doses. However, survival did not improve likely, because this pegylated enzyme does not enter hepatocytes and does not improve hyperammonemia that accounts for lethality. Although murine models required dosing every 48 h, studies in cynomolgus monkeys indicate that less frequent dosing may be possible in patients. Given that elevated plasma arginine rather than hyperammonemia is the major treatment challenge, we propose that AEB1102 may have therapeutic potential as an arginine-reducing agent in patients with arginase deficiency. PMID- 26358774 TI - Insulin response dysregulation explains abnormal fat storage and increased risk of diabetes mellitus type 2 in Cohen Syndrome. AB - Cohen Syndrome (CS) is a rare autosomal recessive disorder, with defective glycosylation secondary to mutations in the VPS13B gene, which encodes a protein of the Golgi apparatus. Besides congenital neutropenia, retinopathy and intellectual deficiency, CS patients are faced with truncal obesity. Metabolism investigations showed abnormal glucose tolerance tests and low HDL values in some patients, and these could be risk factors for the development of diabetes mellitus and/or cardiovascular complications. To understand the mechanisms involved in CS fat storage, we used two models of adipogenesis differentiation: (i) SGBS pre-adipocytes with VPS13B invalidation thanks to siRNA delivery and (ii) CS primary fibroblasts. In both models, VPS13B invalidation led to accelerated differentiation into fat cells, which was confirmed by the earlier and increased expression of specific adipogenic genes, consequent to the increased response of cells to insulin stimulation. At the end of the differentiation protocol, these fat cells exhibited decreased AKT2 phosphorylation after insulin stimulation, which suggests insulin resistance. This study, in association with the in-depth analysis of the metabolic status of the patients, thus allowed us to recommend appropriate nutritional education to prevent the occurrence of diabetes mellitus and to put forward recommendations for the follow-up of CS patients, in particular with regard to the development of metabolic syndrome. We also suggest replacing the term obesity by abnormal fat distribution in CS, which should reduce the number of inappropriate diagnoses in patients who are referred only on the basis of intellectual deficiency associated with obesity. PMID- 26358775 TI - Ultra-structural time-course study in the C. elegans model for Duchenne muscular dystrophy highlights a crucial role for sarcomere-anchoring structures and sarcolemma integrity in the earliest steps of the muscle degeneration process. AB - Duchenne muscular dystrophy (DMD) is a genetic disease characterized by progressive muscle degeneration due to mutations in the dystrophin gene. In spite of great advances in the design of curative treatments, most patients currently receive palliative therapies with steroid molecules such as prednisone or deflazacort thought to act through their immunosuppressive properties. These molecules only slightly slow down the progression of the disease and lead to severe side effects. Fundamental research is still needed to reveal the mechanisms involved in the disease that could be exploited as therapeutic targets. By studying a Caenorhabditis elegans model for DMD, we show here that dystrophin-dependent muscle degeneration is likely to be cell autonomous and affects the muscle cells the most involved in locomotion. We demonstrate that muscle degeneration is dependent on exercise and force production. Exhaustive studies by electron microscopy allowed establishing for the first time the chronology of subcellular events occurring during the entire process of muscle degeneration. This chronology highlighted the crucial role for dystrophin in stabilizing sarcomeric anchoring structures and the sarcolemma. Our results suggest that the disruption of sarcomeric anchoring structures and sarcolemma integrity, observed at the onset of the muscle degeneration process, triggers subcellular consequences that lead to muscle cell death. An ultra-structural analysis of muscle biopsies from DMD patients suggested that the chronology of subcellular events established in C. elegans models the pathogenesis in human. Finally, we found that the loss of sarcolemma integrity was greatly reduced after prednisone treatment suggesting a role for this molecule in plasma membrane stabilization. PMID- 26358773 TI - Reduced sodium/proton exchanger NHE3 activity causes congenital sodium diarrhea. AB - Congenital sodium diarrhea (CSD) refers to an intractable diarrhea of intrauterine onset with high fecal sodium loss. CSD is clinically and genetically heterogeneous. Syndromic CSD is caused by SPINT2 mutations. While we recently described four cases of the non-syndromic form of CSD that were caused by dominant activating mutations in intestinal receptor guanylate cyclase C (GC-C), the genetic cause for the majority of CSD is still unknown. Therefore, we aimed to determine the genetic cause for non-GC-C non-syndromic CSD in 18 patients from 16 unrelated families applying whole-exome sequencing and/or chromosomal microarray analyses and/or direct Sanger sequencing. SLC9A3 missense, splicing and truncation mutations, including an instance of uniparental disomy, and whole gene deletion were identified in nine patients from eight families with CSD. Two of these nine patients developed inflammatory bowel disease (IBD) at 4 and 16 years of age. SLC9A3 encodes Na(+)/H(+) antiporter 3 (NHE3), which is the major intestinal brush-border Na(+)/H(+) exchanger. All mutations were in the NHE3 N terminal transport domain, and all missense mutations were in the putative membrane-spanning domains. Identified SLC9A3 missense mutations were functionally characterized in plasma membrane NHE null fibroblasts. SLC9A3 missense mutations compromised NHE3 activity by reducing basal surface expression and/or loss of basal transport function of NHE3 molecules, whereas acute regulation was normal. This study identifies recessive mutations in NHE3, a downstream target of GC-C, as a cause of CSD and implies primary basal NHE3 malfunction as a predisposition for IBD in a subset of patients. PMID- 26358772 TI - Long-term rescue of cone photoreceptor degeneration in retinitis pigmentosa 2 (RP2)-knockout mice by gene replacement therapy. AB - Retinal neurodegenerative diseases are especially attractive targets for gene replacement therapy, which appears to be clinically effective for several monogenic diseases. X-linked forms of retinitis pigmentosa (XLRP) are relatively severe blinding disorders, resulting from progressive photoreceptor dysfunction primarily caused by mutations in RPGR or RP2 gene. With a goal to develop gene therapy for the XLRP-RP2 disease, we first performed detailed characterization of the Rp2-knockout (Rp2-KO) mice and observed early-onset cone dysfunction, which was followed by progressive cone degeneration, mimicking cone vision impairment in XLRP patients. The mice also exhibited distinct and significantly delayed falling phase of photopic b-wave of electroretinogram (ERG). Concurrently, we generated a self-complementary adeno-associated viral (AAV) vector carrying human RP2-coding sequence and demonstrated its ability to mediate stable RP2 protein expression in mouse photoreceptors. A long-term efficacy study was then conducted in Rp2-KO mice following AAV-RP2 vector administration. Preservation of cone function was achieved with a wide dose range over 18-month duration, as evidenced by photopic ERG and optomotor tests. The slower b-wave kinetics was also completely restored. Morphologically, the treatment preserved cone viability, corrected mis-trafficking of M-cone opsin and restored cone PDE6 expression. The therapeutic effect was achieved even in mice that received treatment at an advanced disease stage. The highest AAV-RP2 dose group demonstrated retinal toxicity, highlighting the importance of careful vector dosing in designing future human trials. The wide range of effective dose, a broad treatment window and long-lasting therapeutic effects should make the RP2 gene therapy attractive for clinical development. PMID- 26358776 TI - Bcl-2/adenovirus E1B 19-kDa interacting protein (BNip3) has a key role in the mitochondrial dysfunction induced by mutant huntingtin. AB - Huntington's disease (HD) is a neurodegenerative disorder caused by the expansion of a CAG repeat in the IT15 gene that encodes the protein huntingtin (htt). Evidence shows that mutant htt causes mitochondrial depolarization and fragmentation, but the underlying molecular mechanism has yet to be clarified. Bax/Bak and BNip3 are pro-apoptotic members of the Bcl-2 family protein whose activation triggers mitochondrial depolarization and fragmentation inducing cell death. Evidence suggests that Bax/Bak and BNip3 undergo activation upon mutant htt expression but whether these proteins are required for mitochondrial depolarization and fragmentation induced by mutant htt is unclear. Our results show that BNip3 knock-out cells are protected from mitochondrial damage and cell death induced by mutant htt whereas Bax/Bak knock-out cells are not. Moreover, deletion of BNip3 C-terminal transmembrane domain, required for mitochondrial targeting, suppresses mitochondrial depolarization and fragmentation in a cell culture model of HD. Hence, our results suggest that changes in mitochondrial morphology and transmembrane potential, induced by mutant htt protein, are dependent and linked to BNip3 and not to Bax/Bak activation. These results provide new compelling evidence that underlies the molecular mechanisms by which mutant htt causes mitochondrial dysfunction and cell death, suggesting BNip3 as a potential target for HD therapy. PMID- 26358777 TI - Two retinal dystrophy-associated missense mutations in GUCA1A with distinct molecular properties result in a similar aberrant regulation of the retinal guanylate cyclase. AB - Two recently identified missense mutations (p. L84F and p. I107T) in GUCA1A, the gene coding for guanylate cyclase (GC)-activating protein 1 (GCAP1), lead to a phenotype ascribable to cone, cone-rod and macular dystrophies. Here, we present a thorough biochemical and biophysical characterization of the mutant proteins and their distinct molecular features. I107T-GCAP1 has nearly wild-type-like protein secondary and tertiary structures, and binds Ca(2+) with a >10-fold lower affinity than the wild-type. On the contrary, L84F-GCAP1 displays altered tertiary structure in both GC-activating and inhibiting states, and a wild type like apparent affinity for Ca(2+). The latter mutant also shows a significantly high affinity for Mg(2+), which might be important for stabilizing the GC activating state and inducing a cooperative mechanism for the binding of Ca(2+), so far not been observed in other GCAP1 variants. Moreover, the thermal stability of L84F-GCAP1 is particularly high in the Ca(2+)-bound, GC-inhibiting state. Molecular dynamics simulations suggest that such enhanced stability arises from a deeper burial of the myristoyl moiety within the EF1-EF2 domain. The simulations also support an allosteric mechanism connecting the myristoyl moiety to the highest-affinity Ca(2+) binding site EF3. In spite of their remarkably distinct molecular features, both mutants cause constitutive activation of the target GC at physiological Ca(2+). We conclude that the similar aberrant regulation of the target enzyme results from a similar perturbation of the GCAP1-GC interaction, which may eventually cause dysregulation of both Ca(2+) and cyclic GMP homeostasis and result in retinal degeneration. PMID- 26358778 TI - CDC174, a novel component of the exon junction complex whose mutation underlies a syndrome of hypotonia and psychomotor developmental delay. AB - Siblings of non-consanguineous Jewish-Ethiopian ancestry presented with congenital axial hypotonia, weakness of the abducens nerve, psychomotor developmental delay with brain ventriculomegaly, variable thinning of corpus callosum and cardiac septal defects. Homozygosity mapping identified a single disease-associated locus of 3.5 Mb on chromosome 3. Studies of a Bedouin consanguineous kindred affected with a similar recessive phenotype identified a single disease-associated 18 Mb homozygosity locus encompassing the entire 3.5 Mb locus. Whole exome sequencing demonstrated only two homozygous mutations within a shared identical haplotype of 0.6 Mb, common to both Bedouin and Ethiopian affected individuals, suggesting an ancient common founder. Only one of the mutations segregated as expected in both kindreds and was not found in Bedouin and Jewish-Ethiopian controls: c.1404A>G, p.[*468Trpext*6] in CCDC174. We showed that CCDC174 is ubiquitous, restricted to the cell nucleus and co-localized with EIF4A3. In fact, yeast-two-hybrid assay demonstrated interaction of CCDC174 with EIF4A3, a component of exon junction complex. Knockdown of the CCDC174 ortholog in Xenopus laevis embryos resulted in poor neural fold closure at the neurula stage with later embryonic lethality. Knockdown embryos exhibited a sharp reduction in expression of n-tubulin, a marker for differentiating primary neurons, and of hindbrain markers krox20 and hoxb3. The Xenopus phenotype could be rescued by the human normal, yet not the mutant CCDC174 transcripts. Moreover, overexpression of mutant but not normal CCDC174 in neuroblastoma cells caused rapid apoptosis. In line with the hypotonia phenotype, the CCDC174 mutation caused depletion of RYR1 and marked myopathic changes in skeletal muscle of affected individuals. PMID- 26358779 TI - The Alzheimer's disease risk factor CD2AP maintains blood-brain barrier integrity. AB - CD2-associated protein (CD2AP) is a leading genetic risk factor for Alzheimer's disease, but little is known about the function of CD2AP in the brain. We studied CD2AP(-/-) mice to address this question. Because CD2AP(-/-) mice normally die by 6 weeks from nephrotic syndrome, we used mice that also express a CD2AP transgene in the kidney, but not brain, to attenuate this phenotype. CD2AP-deficient mice had no behavioral abnormalities except for mild motor and anxiety deficits in a subset of CD2AP(-/-) mice exhibiting severe nephrotic syndrome, associated with systemic illness. Pentylenetetrazol (PTZ)-induced seizures occurred with shorter latency in CD2AP(-/-) mice, but characteristics of these seizures on electroencephalography were not altered. As CD2AP is expressed in brain-adjacent endothelial cells, we hypothesized that the shorter latency to seizures without detectably different seizure characteristics may be due to increased penetration of PTZ related to compromised blood-brain barrier integrity. Using sodium fluorescein extravasation, we found that CD2AP(-/-) mice had reduced blood-brain barrier integrity. Neither seizure severity nor blood-brain barrier integrity was correlated with nephrotic syndrome, indicating that these effects are dissociable from the systemic illness associated with CD2AP deficiency. Confirming this dissociation, wild-type mice with induced nephrotic syndrome maintained an intact blood-brain barrier. Taken together, our results support a role of CD2AP in mediating blood-brain barrier integrity and suggest that cerebrovascular roles of CD2AP could contribute to its effects on Alzheimer's disease risk. PMID- 26358780 TI - Cholesterol 24-hydroxylase defect is implicated in memory impairments associated with Alzheimer-like Tau pathology. AB - Alzheimer's disease (AD) is characterized by both amyloid and Tau pathologies. The amyloid component and altered cholesterol metabolism are closely linked, but the relationship between Tau pathology and cholesterol is currently unclear. Brain cholesterol is synthesized in situ and cannot cross the blood-brain barrier: to be exported from the central nervous system into the blood circuit, excess cholesterol must be converted to 24S-hydroxycholesterol by the cholesterol 24-hydroxylase encoded by the CYP46A1 gene. In AD patients, the concentration of 24S-hydroxycholesterol in the plasma and the cerebrospinal fluid are lower than in healthy controls. The THY-Tau22 mouse is a model of AD-like Tau pathology without amyloid pathology. We used this model to investigate the potential association between Tau pathology and CYP46A1 modulation. The amounts of CYP46A1 and 24S-hydroxycholesterol in the hippocampus were lower in THY-Tau22 than control mice. We used an adeno-associated virus (AAV) gene transfer strategy to increase CYP46A1 expression in order to investigate the consequences on THY-Tau22 mouse phenotype. Injection of the AAV-CYP46A1 vector into the hippocampus of THY Tau22 mice led to CYP46A1 and 24S-hydroxycholesterol content normalization. The cognitive deficits, impaired long-term depression and spine defects that characterize the THY-Tau22 model were completely rescued, whereas Tau hyperphosphorylation and associated gliosis were unaffected. These results argue for a causal link between CYP46A1 protein content and memory impairments that result from Tau pathology. Therefore, CYP46A1 may be a relevant therapeutic target for Tauopathies and especially for AD. PMID- 26358781 TI - Silica modified with a thiourea derivative as a new stationary phase for hydrophilic interaction liquid chromatography. AB - Nowadays there are limited types of commercially available stationary phases for hydrophilic interaction liquid chromatography and therefore new ones with unique selectivity are urgently in demand to meet the need of separations of various polar and hydrophilic analytes. The present study describes the preparation and evaluation of a new stationary phase based on thiourea derivative modified silica for hydrophilic interaction liquid chromatography. Thiourea derivative was bonded onto the surface of silica particles via a mild addition reaction between -NH2 and -SCN, and the result of elemental analysis together with infrared analysis and solid-state NMR spectroscopy proved that the synthesis method was feasible. The new stationary phase succeeded in fast separations of a wide range of polar and hydrophilic analytes and exhibited excellent separation performance, especially unique selectivity. Furthermore, the effects of water content, buffer pH, and salt concentration on retention indicated that a complicated separation mechanism rather than partitioning was involved in the stationary phase and hydrogen bonding interaction between analytes and thiourea functional group could play a very important role in its selectivity. For sure, the new stationary phase is of a great potential as a new type of hydrophilic interaction liquid chromatographic stationary phase. PMID- 26358782 TI - Micro 3D cell culture systems for cellular behavior studies: Culture matrices, devices, substrates, and in-situ sensing methods. AB - Microfabricated systems equipped with 3D cell culture devices and in-situ cellular biosensing tools can be a powerful bionanotechnology platform to investigate a variety of biomedical applications. Various construction substrates such as plastics, glass, and paper are used for microstructures. When selecting a construction substrate, a key consideration is a porous microenvironment that allows for spheroid growth and mimics the extracellular matrix (ECM) of cell aggregates. Various bio-functionalized hydrogels are ideal candidates that mimic the natural ECM for 3D cell culture. When selecting an optimal and appropriate microfabrication method, both the intended use of the system and the characteristics and restrictions of the target cells should be carefully considered. For highly sensitive and near-cell surface detection of excreted cellular compounds, SERS-based microsystems capable of dual modal imaging have the potential to be powerful tools; however, the development of optical reporters and nanoprobes remains a key challenge. We expect that the microsystems capable of both 3D cell culture and cellular response monitoring would serve as excellent tools to provide fundamental cellular behavior information for various biomedical applications such as metastasis, wound healing, high throughput screening, tissue engineering, regenerative medicine, and drug discovery and development. PMID- 26358784 TI - Systematic Assessment of Molecular Selectivity at the Level of Targets, Bioactive Compounds, and Structural Analogues. AB - Through systematic mining of compound activity data, the target selectivity of bioactive compounds was systematically explored. The analysis was facilitated by applying, extending, and combining the concepts of target cliffs, selectivity cliffs, and matched molecular pairs. Selectivity relationships were explored at different levels including targets, individual bioactive compounds, and pairs of structural analogues. A variety of targets were identified for which active compounds were consistently nonselective or, by contrast, exclusively selective, making it possible to prioritize, or de-prioritize, targets for compound development. Furthermore, many chemical modifications were detected that altered compound selectivity in a well-defined manner including small structural changes that converted nonselective into target-selective compounds or inverted the target selectivity of active compounds. A large knowledge base of selectivity relationships across pharmaceutical targets and chemical modifications that alter selectivity was generated; this has been made freely available to the scientific community as a part of this investigation. PMID- 26358785 TI - A European perspective on testicular tissue cryopreservation for fertility preservation in prepubertal and adolescent boys. AB - STUDY QUESTION: What clinical practices, patient management strategies and experimental methods are currently being used to preserve and restore the fertility of prepubertal boys and adolescent males? SUMMARY ANSWER: Based on a review of the clinical literature and research evidence for sperm freezing and testicular tissue cryopreservation, and after consideration of the relevant ethical and legal challenges, an algorithm for the cryopreservation of sperm and testicular tissue is proposed for prepubertal boys and adolescent males at high risk of fertility loss. WHAT IS KNOWN ALREADY: A known late effect of the chemotherapy agents and radiation exposure regimes used to treat childhood cancers and other non-malignant conditions in males is the damage and/or loss of the proliferating spermatogonial stem cells in the testis. Cryopreservation of spermatozoa is the first line treatment for fertility preservation in adolescent males. Where sperm retrieval is impossible, such as in prepubertal boys, or it is unfeasible in adolescents prior to the onset of ablative therapies, alternative experimental treatments such as testicular tissue cryopreservation and the harvesting and banking of isolated spermatogonial stem cells can now be proposed as viable means of preserving fertility. STUDY DESIGN, SIZE, DURATION: Advances in clinical treatments, patient management strategies and the research methods used to preserve sperm and testicular tissue for prepubertal boys and adolescents were reviewed. A snapshot of the up-take of testis cryopreservation as a means to preserve the fertility of young males prior to December 2012 was provided using a questionnaire. PARTICIPANTS/MATERIALS, SETTING, METHODS: A comprehensive literature review was conducted. In addition, survey results of testis freezing practices in young patients were collated from 24 European centres and Israeli University Hospitals. MAIN RESULTS AND THE ROLE OF CHANCE: There is increasing evidence of the use of testicular tissue cryopreservation as a means to preserve the fertility of pre- and peri-pubertal boys of up to 16 year-old. The survey results indicate that of the 14 respondents, half of the centres were actively offering testis tissue cryobanking as a means of safeguarding the future fertility of boys and adolescents as more than 260 young patients (age range less than 1 year old to 16 years of age), had already undergone testicular tissue retrieval and storage for fertility preservation. The remaining centres were considering the implementation of a tissue-based fertility preservation programme for boys undergoing oncological treatments. LIMITATIONS, REASONS FOR CAUTION: The data collected were limited by the scope of the questionnaire, the geographical range of the survey area, and the small number of respondents. WIDER IMPLICATIONS OF THE FINDINGS: The clinical and research questions identified and the ethical and legal issues raised are highly relevant to the multi-disciplinary teams developing treatment strategies to preserve the fertility of prepubertal and adolescent boys who have a high risk of fertility loss due to ablative interventions, trauma or genetic pre-disposition. PMID- 26358783 TI - Pluripotent Conversion of Muscle Stem Cells Without Reprogramming Factors or Small Molecules. AB - Muscle derived stem cells (MDSCs) are multipotent stem cells that can differentiate into several lineages including skeletal muscle precursor cells. Here, we show that MDSCs from myostatin null mice (Mstn (-/-) ) can be readily induced into pluripotent stem cells without using reprogramming factors. Microarray studies revealed a strong upregulation of markers like Leukemia Inhibitory factor (LIF) and Leukemia Inhibitory factor receptor (LIFR) in Mstn ( /-) MDSCs as compared to wild type MDSCs (WT-MDSCs). Furthermore when cultured in mouse embryonic stem cell media with LIF for 95 days, Mstn (-/-) MDSCs formed embryonic stem cell (ES) like colonies. We termed such ES like cells as the culture-induced pluripotent stem cells (CiPSC). CiPSCs from Mstn (-/-) MDSCs were phenotypically similar to ESCs, expressed high levels of Oct4, Nanog, Sox2 and SSEA-1, maintained a normal karyotype. Furthermore, CiPSCs formed embryoid bodies and teratomas when injected into immunocompromised mice. In addition, CiPSCs differentiated into somatic cells of all three lineages. We further show that culturing in ES cell media, resulted in hypermethylation and downregulation of BMP2 in Mstn(-/-) MDSCs. Western blot further confirmed a down regulation of BMP2 signaling in Mstn (-/-) MDSCs in supportive of pluripotent reprogramming. Given that down regulation of BMP2 has been shown to induce pluripotency in cells, we propose that lack of myostatin epigenetically reprograms the MDSCs to become pluripotent stem cells. Thus, here we report the successful establishment of ES like cells from adult stem cells of the non-germline origin under culture-induced conditions without introducing reprogramming genes. PMID- 26358787 TI - Crossing Over. PMID- 26358786 TI - A new phenylethanoid glycoside from Orobanche cernua Loefling. AB - A novel phenylethanoid glycoside, 3'-O-methyl isocrenatoside (1), along with two known compounds, methyl caffeate (2) and protocatechuic aldehyde (3), were isolated from the fresh whole plant of Orobanche cernua Loefling. All the isolated compounds (1-3) were elucidated on the basis of spectroscopic analysis including IR, MS and NMR data. The cytotoxic activities of these compounds were evaluated. Results showed that 3'-O-methyl isocrenatoside (1) and methyl caffeate (2) exhibited significant cytotoxicity, with IC50 values of 71.89, 36.97 MUg/mL and 32.32, 34.58 MUg/mL against the B16F10 murine melanoma and Lewis lung carcinoma cell lines, respectively. PMID- 26358788 TI - Was There a Patient in Your Clinic Today Who Was Distressed? PMID- 26358789 TI - NCCN: The Future is Bright. PMID- 26358790 TI - HER2-Mutated Breast Cancer Responds to Treatment With Single-Agent Neratinib, a Second-Generation HER2/EGFR Tyrosine Kinase Inhibitor. AB - Activating mutations in the HER2 tyrosine kinase have been identified in human breast cancers that lack HER2 gene amplification. These patients are not candidates for HER2-targeted drugs under current standards of care, but preclinical data strongly suggest that these patients will benefit from anti-HER2 drugs. This case report describes a young woman with metastatic breast cancer whose tumor was found to carry a HER2 L755S mutation, which is in the kinase domain of HER2. Treatment with the second-generation HER2/EGFR tyrosine kinase inhibitor neratinib resulted in partial response and dramatic improvement in the patient's functional status. This partial response lasted 11 months, and when the patient's cancer progressed, she was treated with neratinib plus capecitabine and her cancer again responded. This second response parallels the benefit seen with continuing trastuzumab in HER2-amplified breast cancer after disease progression. This case represents the first report, to our knowledge, of successful single agent treatment of HER2-mutated breast cancer. Two clinical trials of neratinib for HER2-mutated metastatic breast cancer are currently enrolling patients. Further, data from The Cancer Genome Atlas project have identified HER2 mutations in a wide range of solid tumors, including bladder, colorectal, and non-small cell lung cancers, suggesting that clinical trials of neratinib or neratinib based combinations for HER2-mutated solid tumors is warranted. PMID- 26358791 TI - Prolonged Response to Trastuzumab in a Patient With HER2-Nonamplified Breast Cancer With Elevated HER2 Dimerization Harboring an ERBB2 S310F Mutation. AB - In the current genomic era, increasing evidence demonstrates that approximately 2% of HER2-negative breast cancers, by current standard testings, harbor activating mutations of ERBB2. However, whether patients with HER2-negative breast cancer with activating mutations of ERBB2 also experience response to anti HER2 therapies remains unclear. This case report describes a patient with HER2 nonamplified heavily pretreated breast cancer who experienced prolonged response to trastuzumab in combination with pertuzumab and fulvestrant. Further molecular analysis demonstrated that her tumors had an elevated HER2 dimerization that corresponded to ERBB2 S310F mutation. Located in the extracellular domain of the HER2 protein, this mutation was reported to promote noncovalent dimerization that results in the activation of the downstream signaling pathways. This case highlights the fact that HER2-targeted therapy may be valuable in patients harboring an ERBB2 S310F mutation. PMID- 26358792 TI - Cancer-Associated Venous Thromboembolic Disease, Version 1.2015. AB - The NCCN Guidelines for Cancer-Associated Venous Thromboembolic Disease outline strategies for treatment and prevention of venous thromboembolism (VTE) in adult patients with a diagnosis of cancer or for whom cancer is clinically suspected. VTE is a common complication in patients with cancer, which places them at greater risk for morbidity and mortality. Therefore, risk-appropriate prophylaxis is an essential component for the optimal care of inpatients and outpatients with cancer. Critical to meeting this goal is ensuring that patients get the most effective medication in the correct dose. Body weight has a significant impact on blood volume and drug clearance. Because obesity is a common health problem in industrialized societies, cancer care providers are increasingly likely to treat obese patients in their practice. Obesity is a risk factor common to VTE and many cancers, and may also impact the anticoagulant dose needed for safe and effective prophylaxis. These NCCN Guidelines Insights summarize the data supporting new dosing recommendations for VTE prophylaxis in obese patients with cancer. PMID- 26358793 TI - Calcium and Magnesium Use for Oxaliplatin-Induced Neuropathy: A Case Study to Assess How Quickly Evidence Translates Into Practice. AB - Substantial research efforts have focused on methods of treating and preventing oxaliplatin-associated neuropathy, the dose-limiting toxicity associated with this drug. Administration of intravenous calcium and magnesium (CaMg) before and after oxaliplatin has been the most studied approach to preventing oxaliplatin induced neuropathy. Although early reports demonstrated potential benefit, subsequent larger trials failed to confirm the efficacy of CaMg in preventing this adverse effect. This article explores how accumulating evidence for and against the use of CaMg for preventing oxaliplatin-induced neuropathy has impacted clinical practice. PMID- 26358794 TI - Effectiveness of Initial Transarterial Chemoembolization for Hepatocellular Carcinoma Among Medicare Beneficiaries. AB - BACKGROUND: Optimal administration of transarterial chemoembolization (TACE), the standard approach for intermediate-stage hepatocellular carcinoma (HCC), requires clinical and technical expertise. We sought to evaluate whether TACE retains its effectiveness when administered across a broad range of health care settings. Furthermore, as the use of yttrium(90) (Y(90)) radioembolization has been increasing, we explored the comparative effectiveness of Y(90) as an alternative to TACE. METHODS: Patients with HCC diagnosed from 2004 through 2009 treated initially with TACE or Y(90) were identified from the SEER-Medicare linkage. Key covariates included prediagnosis alpha-fetoprotein (AFP) screening, complications of cirrhosis, and tumor extent. Effect of treatment, patient, and health care system factors on overall survival (OS) was evaluated using multivariable Cox proportional hazards. Stratified OS estimates are provided. Propensity score (PS) weighting was used to compare effectiveness of Y(90) with TACE. RESULTS: Of 1528 patients who underwent intra-arterial embolization, 577 received concurrent chemotherapy (eg, TACE). Median OS was 21 months (95% CI, 18-23) following TACE and 9 months (95% CI, 1-41) following Y(90). Refined survival estimates stratified by stage, AFP screening, and liver comorbidity are presented. The 90 day mortality rate after TACE was 21% to 25% in patients with extrahepatic spread or vascular invasion. In the PS-weighted analysis, Y(90) was associated with inferior survival, with an adjusted hazard ratio of 1.39 (95% CI, 1.02-1.90). CONCLUSIONS: The effectiveness of TACE is generalizable to Medicare patients receiving care in a variety of treatment settings. However, early posttreatment mortality is high in patients with advanced disease. We found no evidence of improved outcomes with Y(90) compared with TACE. Survival estimates from this large cohort can be used to provide prognostic information to patients considering palliative TACE. PMID- 26358795 TI - Reduced Circumferential Resection Margin Involvement in Rectal Cancer Surgery: Results of the Dutch Surgical Colorectal Audit. AB - BACKGROUND: The circumferential resection margin (CRM) is a significant prognostic factor for local recurrence, distant metastasis, and survival after rectal cancer surgery. Therefore, availability of this parameter is essential. Although the Dutch total mesorectal excision trial raised awareness about CRM in the late 1990s, quality assurance on pathologic reporting was not available until the Dutch Surgical Colorectal Audit (DSCA) started in 2009. The present study describes the rates of CRM reporting and involvement since the start of the DSCA and analyzes whether improvement of these parameters can be attributed to the audit. METHODS: Data from the DSCA (2009-2013) were analyzed. Reporting of CRM and CRM involvement was plotted for successive years, and variations of these parameters were analyzed in a funnelplot. Predictors of CRM involvement were determined in univariable analysis and the independent influence of year of registration on CRM involvement was analyzed in multivariable analysis. RESULTS: A total of 12,669 patients were included for analysis. The mean percentage of patients with a reported CRM increased from 52.7% to 94.2% (2009-2013) and interhospital variation decreased. The percentage of patients with CRM involvement decreased from 14.2% to 5.6%. In multivariable analysis, the year of DSCA registration remained a significant predictor of CRM involvement. CONCLUSIONS: After the introduction of the DSCA, a dramatic improvement in CRM reporting and a major decrease of CRM involvement after rectal cancer surgery have occurred. This study suggests that a national quality assurance program has been the driving force behind these achievements. PMID- 26358796 TI - Geriatric Assessment-Guided Care Processes for Older Adults: A Delphi Consensus of Geriatric Oncology Experts. AB - BACKGROUND: Structured care processes that provide a framework for how oncologists can incorporate geriatric assessment (GA) into clinical practice could improve outcomes for vulnerable older adults with cancer, a growing population at high risk of toxicity from cancer treatment. We sought to obtain consensus from an expert panel on the use of GA in clinical practice and to develop algorithms of GA-guided care processes. METHODS: The Delphi technique, a well-recognized structured and reiterative process to reach consensus, was used. Participants were geriatric oncology experts who attended NIH-funded U13 or Cancer and Aging Research Group conferences. Consensus was defined as an interquartile range of 2 or more units, or 66.7% or greater, selecting a utility/helpfulness rating of 7 or greater on a 10-point Likert scale. For nominal data, consensus was defined as agreement among 66.7% or more of the group. RESULTS: From 33 invited, 30 participants completed all 3 rounds. Most experts (75%) used GA in clinical care, and the remainder were involved in geriatric oncology research. The panel met consensus that "all patients aged 75 years or older and those who are younger with age-related health concerns" should undergo GA and that all domains (function, physical performance, comorbidity/polypharmacy, cognition, nutrition, psychological status, and social support) should be included. Consensus was met for how GA could guide nononcologic interventions and cancer treatment decisions. Algorithms for GA guided care processes were developed. CONCLUSIONS: This Delphi investigation of geriatric oncology experts demonstrated that GA should be performed for older patients with cancer to guide care processes. PMID- 26358797 TI - Racial Disparities in End-of-Life Care Among Patients With Prostate Cancer: A Population-Based Study. AB - OBJECTIVE: To examine racial disparities in end-of-life (EOL) care among black and white patients dying of prostate cancer (PCa). METHODS: Relying on the SEER Medicare database, 3789 patients who died of metastatic PCa between 1999 and 2009 were identified. Information was assessed regarding diagnostic care, therapeutic interventions, hospitalizations, intensive care unit (ICU) admissions, and emergency department visits in the last 12 months, 3 months, and 1 month of life. Logistic regression tested the relationship between race and the receipt of diagnostic care, therapeutic interventions, and high-intensity EOL care. RESULTS: Overall, 729 patients (19.24%) were black. In the 12-months preceding death, laboratory tests (odds ratio [OR], 0.51; 95% CI, 0.36-0.72), prostate-specific antigen test (OR, 0.54; 95% CI, 0.43-0.67), cystourethroscopy (OR, 0.71; 95% CI, 0.56-0.90), imaging procedure (OR, 0.58; 95% CI, 0.41-0.81), hormonal therapy (OR, 0.53; 95% CI, 0.44-0.65), chemotherapy (OR, 0.59; 95% CI, 0.48-0.72), radiotherapy (OR, 0.74; 95% CI, 0.61-0.90), and office visit (OR, 0.38; 95% CI, 0.28-0.50) were less frequent in black versus white patients. Conversely, high intensity EOL care, such as ICU admission (OR, 1.27; 95% CI, 1.04-1.58), inpatient admission (OR, 1.49; 95% CI, 1.09-2.05), and cardiopulmonary resuscitation (OR, 1.72; 95% CI, 1.40-2.11), was more frequent in black versus white patients. Similar trends for EOL care were observed at 3-month and 1-month end points. CONCLUSIONS: Although diagnostic and therapeutic interventions are less frequent in black patients with end-stage PCa, the rate of high-intensity and aggressive EOL care is higher in these individuals. These disparities may indicate that race plays an important role in the quality of care for men with end-stage PCa. PMID- 26358798 TI - Anaplastic Thyroid Carcinoma, Version 2.2015. AB - This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Thyroid Carcinoma focuses on anaplastic carcinoma because substantial changes were made to the systemic therapy recommendations for the 2015 update. Dosages and frequency of administration are now provided, docetaxel/doxorubicin regimens were added, and single-agent cisplatin was deleted because it is not recommended for patients with advanced or metastatic anaplastic thyroid cancer. PMID- 26358800 TI - It May Be Time to Abandon Urine Tests for Bladder Cancer. PMID- 26358802 TI - Computational Chemistry in the Pharmaceutical Industry: From Childhood to Adolescence. AB - Computational chemistry within the pharmaceutical industry has grown into a field that proactively contributes to many aspects of drug design, including target selection and lead identification and optimization. While methodological advancements have been key to this development, organizational developments have been crucial to our success as well. In particular, the interaction between computational and medicinal chemistry and the integration of computational chemistry into the entire drug discovery process have been invaluable. Over the past ten years we have shaped and developed a highly efficient computational chemistry group for small-molecule drug discovery at Bayer HealthCare that has significantly impacted the clinical development pipeline. In this article we describe the setup and tasks of the computational group and discuss external collaborations. We explain what we have found to be the most valuable and productive methods and discuss future directions for computational chemistry method development. We share this information with the hope of igniting interesting discussions around this topic. PMID- 26358799 TI - Survivorship in Non-Small Cell Lung Cancer: Challenges Faced and Steps Forward. AB - Improvements in curative therapies and the advent of screening have led to increased numbers of non-small cell lung cancer (NSCLC) survivors. Most survivors have undergone invasive treatment (surgery, radiation therapy, and/or chemotherapy) and carry a higher comorbidity burden than survivors of other cancers. Overall quality of life (QOL) and health-related quality of life (HRQOL) suffer during the treatment phase, with the potential for long-term decline, and both clinical characteristics and treatment impact these measures. Physical and mental components of HRQOL seem to be most at risk for decline. The issues faced by survivors include physical symptoms such as respiratory issues, fatigue, hearing loss, neuropathy, and postsurgical pain; psychological distress leading to depression, financial issues, and poor compliance with recommended guidelines; and fear or risk of recurrence and secondary malignancies. This article summarizes the major issues faced by NSCLC survivors and suggests appropriate management. Future collaborative efforts are needed to further elucidate the complex issues that affect overall QOL and HRQOL in NSCLC survivors and to develop appropriate interventions in this large and diverse survivor population. PMID- 26358803 TI - Hepatoprotective phenylethanoid glycosides from Cirsium setosum. AB - Two new phenylethanoid glycosides, namely beta-D-glucopyranoside, 1"-O-(7S)-7-(3 methoxyl-4-hydroxyphenyl)-7-methoxyethyl-3"-alpha-L-rhamnopyranosyl-4"-[(8E)-7-(3 methoxyl-4-hydroxyphenyl)-8-propenoate] (1) and beta-D-glucopyranoside, 1"-O-(7S) 7-(3-methoxyl-4-hydroxyphenyl)-7-methoxyethyl-3"-alpha-L-rhamnopyranosyl-4"-[(8E) 7-(4-hydroxyphenyl)-8-propenoate] (2), together with six phenylethanoid glycosides were isolated from Cirsium setosum. Their structures were elucidated by their spectroscopic data and references. Compounds 2, 4, 5, 7 and 8 (10 MUM) exhibited moderate hepatoprotective activities. Compounds (3-8) were obtained from this plant for the first time. PMID- 26358804 TI - Epidemiology of medications use in pregnancy. AB - The use of prescribed and over-the-counter medications in pregnancy is on the rise. Many women become pregnant at an older age and with preexisting medical conditions that require pharmacotherapy. In addition, pregnancy is associated with profound changes in the physiology of virtually every organ in the body, which affect medications' pharmacokinetics and pharmacodynamics. Despite all of these, pregnant women are still considered therapeutic orphans, as the majority of current therapeutics were never studied in pregnancy. The goals of this review are to synthesize the available information regarding the epidemiology of medications use and the state of drug research in pregnancy, in an effort to highlight the need for pharmacologic research in pregnancy. PMID- 26358806 TI - Introduction. PMID- 26358805 TI - Pharmacologic studies in vulnerable populations: Using the pediatric experience. AB - Historically, few data exist to guide dosing in children and pregnant women. Multiple barriers to inclusion of these vulnerable populations in clinical trials have led to this paucity of data. However, federal legislation targeted at pediatric therapeutics, innovative clinical trial design, use of quantitative clinical pharmacology methods, pediatric thought leadership, and collaboration have successfully overcome many existing barriers. This success has resulted in improved knowledge on pharmacokinetics, safety, and efficacy of therapeutics in children. To date, research in pregnant women has not been characterized by similar success. Wide gaps in knowledge remain despite the common use of therapeutics in pregnancy. Given the similar barriers to drug research and development in pediatric and pregnant populations, the route toward success in children may serve as a model for the advancement of drug development and appropriate drug administration in pregnant women. PMID- 26358807 TI - Proteomic and lipidomic analyses of paraoxonase defined high density lipoprotein particles: Association of paraoxonase with the anti-coagulant, protein S. AB - PURPOSE: Characterizing high density lipoprotein (HDL) particles and their relevance to HDL function is a major research objective. One aim is to identify functionally distinct particles. To try to limit both functional and compositional heterogeneity the present study focused on paraoxonase-1 (PON1) as a target for isolation of a minor HDL subfraction. EXPERIMENTAL DESIGN: Immunoaffinity techniques were applied to isolate PON1-containing HDL (P-HDL) and total HDL (T-HDL), which were subsequently characterized and compared. RESULTS: Analyses of the lipidomes showed significant differences between the fractions in the relative concentrations of individual lipid subspecies, notably reduced levels of unsaturated lysophosphatidylcholine (p < 0.05) in P-HDL (reflected in a significantly reduced total lysophosphatidylcholine polyunsaturated fatty acid content, p < 0.004). Significant differences were also observed for the proteomes. P-HDL was highly enriched in the anti-coagulant, vitamin K activated protein S (prot S) (p < 0.0001), and alpha2 macroglobulin (p < 0.01), compared to T-HDL. Conversely, procoagulant proteins kininogen 1 and histidine-rich glycoprotein were largely excluded from P-HDL. Immunoabsorption of PON1 from plasma significantly reduced prot S anti-coagulant activity. CONCLUSIONS AND CLINICAL RELEVANCE: The P-HDL lipidome and proteome showed significant differences from T-HDL. Enrichment in anti-coagulation proteins indicates complementary functionalities within P-HDL particles and underlines their anti atherosclerotic potential. PMID- 26358808 TI - Virtual screening of chemical compounds active against breast cancer cell lines based on cell cycle modelling, prediction of cytotoxicity and interaction with targets. AB - Bio- and chemoinformatics methods are widely used for the detection of mechanisms of cancer, to search for potential drug targets and their ligands. Regulatory network analysis based on signalling pathways, and cell cycle regulation provides better understanding of diseases with multiple mechanisms of pathogenesis. We developed an approach for in silico prediction of the cytotoxic effect of chemical compounds in non-transformed and breast cancer cell lines. This approach combines the prediction of the interaction between chemical compounds and human proteins, cytotoxicity and regulatory network modelling taking into account gene expression. Application of our approach to virtual screening of libraries of commercially available compounds allowed selection of dozens of promising hits. These molecules are predicted to interact with the identified targets and exhibit cytotoxicity against breast cancer cell lines but not non-tumour human cell lines. Experimental testing of 49 selected compounds against MDA-MB-231 and MCF7 breast cancer cell lines confirmed the activity of eight compounds with IC50 values ranged from 0.8 to 50 MUM. Thus, the developed approach may be applied for virtual screening for cytotoxic compounds against tumour cell lines. PMID- 26358809 TI - ATP dependent NS3 helicase interaction with RNA: insights from molecular simulations. AB - Non-structural protein 3 (NS3) helicase from hepatitis C virus is an enzyme that unwinds and translocates along nucleic acids with an ATP-dependent mechanism and has a key role in the replication of the viral RNA. An inchworm-like mechanism for translocation has been proposed based on crystal structures and single molecule experiments. We here perform atomistic molecular dynamics in explicit solvent on the microsecond time scale of the available experimental structures. We also construct and simulate putative intermediates for the translocation process, and we perform non-equilibrium targeted simulations to estimate their relative stability. For each of the simulated structures we carefully characterize the available conformational space, the ligand binding pocket, and the RNA binding cleft. The analysis of the hydrogen bond network and of the non equilibrium trajectories indicates an ATP-dependent stabilization of one of the protein conformers. Additionally, enthalpy calculations suggest that entropic effects might be crucial for the stabilization of the experimentally observed structures. PMID- 26358811 TI - Lack of correlation between reaction speed and analytical sensitivity in isothermal amplification reveals the value of digital methods for optimization: validation using digital real-time RT-LAMP. AB - In this paper, we asked if it is possible to identify the best primers and reaction conditions based on improvements in reaction speed when optimizing isothermal reactions. We used digital single-molecule, real-time analyses of both speed and efficiency of isothermal amplification reactions, which revealed that improvements in the speed of isothermal amplification reactions did not always correlate with improvements in digital efficiency (the fraction of molecules that amplify) or with analytical sensitivity. However, we observed that the speeds of amplification for single-molecule (in a digital device) and multi-molecule (e.g. in a PCR well plate) formats always correlated for the same conditions. Also, digital efficiency correlated with the analytical sensitivity of the same reaction performed in a multi-molecule format. Our finding was supported experimentally with examples of primer design, the use or exclusion of loop primers in different combinations, and the use of different enzyme mixtures in one-step reverse-transcription loop-mediated amplification (RT-LAMP). Our results show that measuring the digital efficiency of amplification of single-template molecules allows quick, reliable comparisons of the analytical sensitivity of reactions under any two tested conditions, independent of the speeds of the isothermal amplification reactions. PMID- 26358813 TI - An atlas of RNA base pairs involving modified nucleobases with optimal geometries and accurate energies. PMID- 26358810 TI - Characterization of a cAMP responsive transcription factor, Cmr (Rv1675c), in TB complex mycobacteria reveals overlap with the DosR (DevR) dormancy regulon. AB - Mycobacterium tuberculosis (Mtb) Cmr (Rv1675c) is a CRP/FNR family transcription factor known to be responsive to cAMP levels and during macrophage infections. However, Cmr's DNA binding properties, cellular targets and overall role in tuberculosis (TB) complex bacteria have not been characterized. In this study, we used experimental and computational approaches to characterize Cmr's DNA binding properties and identify a putative regulon. Cmr binds a 16-bp palindromic site that includes four highly conserved nucleotides that are required for DNA binding. A total of 368 binding sites, distributed in clusters among ~200 binding regions throughout the Mycobacterium bovis BCG genome, were identified using ChIP seq. One of the most enriched Cmr binding sites was located upstream of the cmr promoter, and we demonstrated that expression of cmr is autoregulated. cAMP affected Cmr binding at a subset of DNA loci in vivo and in vitro, including multiple sites adjacent to members of the DosR (DevR) dormancy regulon. Our findings of cooperative binding of Cmr to these DNA regions and the regulation by Cmr of the DosR-regulated virulence gene Rv2623 demonstrate the complexity of Cmr mediated gene regulation and suggest a role for Cmr in the biology of persistent TB infection. PMID- 26358814 TI - US prison directors' group calls for reduced use of solitary confinement. PMID- 26358812 TI - Thymine DNA glycosylase exhibits negligible affinity for nucleobases that it removes from DNA. AB - Thymine DNA Glycosylase (TDG) performs essential functions in maintaining genetic integrity and epigenetic regulation. Initiating base excision repair, TDG removes thymine from mutagenic G .: T mispairs caused by 5-methylcytosine (mC) deamination and other lesions including uracil (U) and 5-hydroxymethyluracil (hmU). In DNA demethylation, TDG excises 5-formylcytosine (fC) and 5 carboxylcytosine (caC), which are generated from mC by Tet (ten-eleven translocation) enzymes. Using improved crystallization conditions, we solved high resolution (up to 1.45 A) structures of TDG enzyme-product complexes generated from substrates including G.U, G.T, G.hmU, G.fC and G.caC. The structures reveal many new features, including key water-mediated enzyme-substrate interactions. Together with nuclear magnetic resonance experiments, the structures demonstrate that TDG releases the excised base from its tight product complex with abasic DNA, contrary to previous reports. Moreover, DNA-free TDG exhibits no significant binding to free nucleobases (U, T, hmU), indicating a Kd >> 10 mM. The structures reveal a solvent-filled channel to the active site, which might facilitate dissociation of the excised base and enable caC excision, which involves solvent mediated acid catalysis. Dissociation of the excised base allows TDG to bind the beta rather than the alpha anomer of the abasic sugar, which might stabilize the enzyme-product complex. PMID- 26358815 TI - Revisiting cardiovascular calcification: A multifaceted disease requiring a multidisciplinary approach. AB - The presence of cardiovascular calcification significantly predicts patients' morbidity and mortality. Calcific mineral deposition within the soft cardiovascular tissues disrupts the normal biomechanical function of these tissues, leading to complications such as heart failure, myocardial infarction, and stroke. The realization that calcification results from active cellular processes offers hope that therapeutic intervention may prevent or reverse the disease. To this point, however, no clinically viable therapies have emerged. This may be due to the lack of certainty that remains in the mechanisms by which mineral is deposited in cardiovascular tissues. Gaining new insight into this process requires a multidisciplinary approach. The pathological changes in cell phenotype that lead to the physicochemical deposition of mineral and the resultant effects on tissue biomechanics must all be considered when designing strategies to treat cardiovascular calcification. In this review, we overview the current cardiovascular calcification paradigm and discuss emerging techniques that are providing new insight into the mechanisms of ectopic calcification. PMID- 26358816 TI - Sofosbuvir plus simeprevir treatment of recurrent genotype 1 hepatitis C after liver transplant. AB - BACKGROUND: Patients with recurrent hepatitis C (HCV) infection post-liver transplant can be difficult to treat safely and effectively. A prior (COSMOS) study in patients with non-transplant HCV, using sofosbuvir plus simeprevir, had high efficacy and tolerability in treating patients with HCV genotype 1, even prior non-responders to interferon therapy and those with cirrhosis. Our aim was to evaluate the efficacy of sofosbuvir and simeprevir in patients with genotype 1 HCV post-liver transplant. METHODS: In this prospective, observational study, patients received sofosbuvir 400 mg plus simeprevir 150 mg daily for 12 wk without ribavirin. The primary end point was a sustained virologic response 12 wk after the end of therapy. RESULTS: Forty-two patients completed the treatment. Twenty-six percent started the treatment <= 6 months post-liver transplant. Nineteen percent of the included patients had cirrhosis, 14% with decompensation. At week 4 on the treatment, 21% of patients had detectable virus but at the end of the treatment, 100% were undetectable. Twelve weeks after the end of the treatment, 95% of the patients had undetectable hepatitis C. The regimen was generally well tolerated. CONCLUSION: The oral regimen of sofosbuvir plus simeprevir without ribavirin is efficacious and well tolerated in the treatment of patients with genotype 1 hepatitis C post-liver transplant. PMID- 26358817 TI - Genetic identification and phylogenetic relationships of Indian clariids based on mitochondrial COI sequences. AB - Mitochondrial cytochrome C Oxidase I (COI) sequence variation among the clariid fishes of India (Clarias magur, C. dussumieri and C. gariepinus) and their relationship with other representative clariids was studied in this work. Three species were sampled and together with 23 COI sequences from GenBank were used to reconstruct phylogenetic relationships in the family Clariidae. The study revealed two clades: one consisting of the African species with C. dussumieri, and the other of Asian species suggesting the prevalence of intra-continental diversification of catfishes. This study further revealed that the genus Clarias is monophyletic. For the COI gene, the interspecies genetic divergence ranged from 0.056 to 0.182. The mean genetic difference between C. dussumieri and other selected African species in this study is 12.1%. It was also observed that the morphological similarity of C. dussumieri and C. magur was not replicated in the genetic level. Clarias dussumieri was more close to African catfish C. gariepinus thus indicating the utility of COI phylogeny to identify the well-known African Asian relationships within catfishes. The results also showed that C. magur and C. batrachus are genetically distinct from each other. PMID- 26358818 TI - Assessment of Intramedullary Spinal Pressure in Small Breed Dogs With Thoracolumbar Disk Extrusion Undergoing Hemilaminectomy. AB - OBJECTIVE: To assess intramedullary spinal pressure (IMP) in small breed dogs with thoracolumbar disk extrusion. STUDY DESIGN: Prospective cohort study. ANIMALS: Small breed dogs (n = 14) with thoracolumbar disk extrusion undergoing hemilaminectomy and healthy chondrodystrophic laboratory dogs (control; n = 3) without spinal disease. METHODS: Diagnosis was based on clinical and neurological examinations and magnetic resonance imaging (MRI) and was confirmed intraoperatively. A standardized anesthesia protocol and surgical procedure were used to minimize factors that could influence IMP. Intramedullary pressure was measured through a minidurotomy at the site of spinal cord compression using a fiber optic catheter inserted perpendicular to the longitudinal axis of the spinal cord. Measurements were taken after hemilaminectomy and again after removal of extruded disk material. RESULTS: Affected dogs had significantly higher IMP compared to control dogs (P = .008) and IMP decreased significantly post-decompression compared with initial values (P < .001). No correlation was found between IMP and neurologic grade, degree of spinal cord compression on MRI, or signal intensity changes on MRI. CONCLUSION: Acute thoracolumbar disk extrusion is associated with increased IMP in small breed dogs and surgical decompression results in an immediate decrease of IMP. PMID- 26358819 TI - Development of photostabilized asymmetrical cyanine dyes for in vivo photoacoustic imaging of tumors. AB - Photoacoustic imaging (PAI) contributes to tumor diagnosis through the use of PAI probes that effectively accumulate in tumors. Previously, we developed a symmetrical cyanine dye, IC7-1-Bu, which showed high potential as a PAI probe because of its high tumor targeting ability and sufficient in vivo PA signal. However, IC7-1-Bu lacks photostability for multiple laser irradiations, so we developed stabilized PAI probes using IC7-1-Bu as a lead compound. We focused on the effect of singlet oxygen (1O2) generated by excited PAI probes on probe degeneration. We introduced a triplet-state quencher (TSQ) moiety into IC7-1-Bu to quench 1O2 generation and designed three IC-n-T derivatives with different linker lengths (n indicates linker length). The IC-n-T derivatives emitted in vitro PA signals that were comparable to IC7-1-Bu and significantly reduced 1O2 generation while showing improved photostability against multiple irradiations. Of the three derivatives evaluated, IC-5-T accumulated in tumors effectively to allow clear PAI of tumors in vivo. Furthermore, the photostability of IC-5-T was 1.5-fold higher than that of IC7-1-Bu in in vivo sequential PAI. These results suggest that IC-5-T is a potential PAI probe for in vivo sequential tumor imaging. PMID- 26358820 TI - Monitoring the progression from intraductal carcinoma to invasive ductal carcinoma based on multiphoton microscopy. AB - Intraductal carcinoma is a precancerous lesion of the breast and the immediate precursor of invasive ductal carcinoma. Multiphoton microscopy (MPM) was used to monitor the progression from intraductal carcinoma to invasive ductal carcinoma, which can improve early detection of precursor lesions and halt progression to invasive neoplastic disease. It was found that MPM has the capability to reveal the qualitative changes in features of cells, structure of basement membranes, and architecture of collagens during the development from intraductal carcinoma to invasive ductal carcinoma, as well as the quantitative alterations in nuclear area, circle length of basement membrane, and collagen density. Combined with intra-fiberoptic ductoscopy or transdermal biopsy needle, MPM has the potential to provide immediate histological diagnosis of tumor progression in the field of breast carcinoma. PMID- 26358821 TI - Functional response of cerebral blood flow induced by somatosensory stimulation in rats with subarachnoid hemorrhage. AB - Subarachnoid hemorrhage (SAH) is often accompanied by cerebral vasospasm (CVS), which is the phenomenon of narrowing of large cerebral arteries, and then can produce delayed ischemic neurological deficit (DIND) such as lateralized sensory dysfunction. CVS was regarded as a major contributor to DIND in patients with SAH. However, therapy for preventing vasospasm after SAH to improve the outcomes may not work all the time. It is important to find answers to the relationship between CVS and DIND after SAH. How local cerebral blood flow (CBF) is regulated during functional activation after SAH still remains poorly understood, whereas, the regulation of CBF may play an important role in weakening the impact of CVS on cortex function. Therefore, it is worthwhile to evaluate the functional response of CBF in the activated cortex in an SAH animal model. Most evaluation of the effect of SAH is presently carried out by neurological behavioral scales. The functional imaging of cortical activation during sensory stimulation may help to reflect the function of the somatosensory cortex more locally than the behavioral scales do. We investigated the functional response of CBF in the somatosensory cortex induced by an electrical stimulation to contralateral forepaw via laser speckle imaging in a rat SAH model. Nineteen Sprague-Dawley rats from two groups (control group, n=10 and SAH group, n=9) were studied. SAH was induced in rats by double injection of autologous blood into the cisterna magna after CSF aspiration. The same surgical procedure was applied in the control group without CSF aspiration or blood injection. Significant CVS was found in the SAH group. Meanwhile, we observed a delayed peak of CBF response in rats with SAH compared with those in the control group, whereas no significant difference was found in magnitude, duration, and areas under curve of relative CBF changes between the two groups. The results suggest that the regulation function of local CBF during functional activation induced by somatosensory stimulation might not be seriously impaired in the somatosensory cortex of rats with SAH. Therefore, our findings might help to understand the clinical phenomenon that DIND might not occur even when CVS was found in SAH patients. PMID- 26358822 TI - Calcium neuroimaging in behaving zebrafish larvae using a turn-key light field camera. AB - Reconstructing a three-dimensional scene from multiple simultaneously acquired perspectives (the light field) is an elegant scanless imaging concept that can exceed the temporal resolution of currently available scanning-based imaging methods for capturing fast cellular processes. We tested the performance of commercially available light field cameras on a fluorescent microscopy setup for monitoring calcium activity in the brain of awake and behaving reporter zebrafish larvae. The plenoptic imaging system could volumetrically resolve diverse neuronal response profiles throughout the zebrafish brain upon stimulation with an aversive odorant. Behavioral responses of the reporter fish could be captured simultaneously together with depth-resolved neuronal activity. Overall, our assessment showed that with some optimizations for fluorescence microscopy applications, commercial light field cameras have the potential of becoming an attractive alternative to custom-built systems to accelerate molecular imaging research on cellular dynamics. PMID- 26358823 TI - Compact wearable dual-mode imaging system for real-time fluorescence image-guided surgery. AB - A wearable all-plastic imaging system for real-time fluorescence image-guided surgery is presented. The compact size of the system is especially suitable for applications in the operating room. The system consists of a dual-mode imaging system, see-through goggle, autofocusing, and auto-contrast tuning modules. The paper will discuss the system design and demonstrate the system performance. PMID- 26358824 TI - In vitro effects of extracellular hypercapnic acidification on the reactivity of rat aorta: Rat aorta vasodilation during hypercapnic acidification. AB - : The mechanisms by which pH influences vascular tone are not entirely understood, but evidence suggests that the endothelium is involved. Here, we aimed to study the in vitro vascular responses induced by extracellular hypercapnic acidification (HA), as well as the endothelium-dependent mechanisms that are involved in the responses. We bubbled a mixture of CO2 (40%)/O2 (60%) in an organ bath; we constructed a pH-response curve (pH range 7.4-6.6) and registered isometric force simultaneously. Aortic rings from rats were pre contracted with phenylephrine (10-6 M) and incubated for 30 min in the presence of different chemicals. The relaxations induced by HA occurred in rings with endothelium were: 1) Partially inhibited by indomethacin (10-5 M) (PGI2 pathway inhibitor); 2) Strongly inhibited by NO pathways: L-NAME (10-4 M) and L-NMMA (10 4 M) (no specific NO synthase inhibitors); L-Nil (10-3 M) (specific iNOS inhibitor); ODQ (10-4 M) (specific guanylate cyclase inhibitor), and; 4) Inhibit by tetraethylammonium (10-3 M) (non-specific potassium channel inhibitor), glibenclamide (10-5 M) (specific KATP inhibitor), aminopyridine (10-3 M) (specific Kv inhibitor) and apamin (10-6 M) (specific SKCa inhibitor). IN CONCLUSION: 1) HA causes endothelium-dependent relaxation; 2) Indomethacin failed in blocking this relaxation, but the method limitation does not allow ruling out some prostanoid role; 3) The HA vessel relaxation is mediated via cGMP/NO, and; 4) The hyperpolarization occurs by the action of potassium SKCa, KATP and Kv channels without relying on BKCa channels. PMID- 26358825 TI - Complete mitochondrial genome of the white char Salvelinus albus (Salmoniformes, Salmonidae). AB - The complete mitochondrial genome was sequenced in two individuals of white char Salvelinus albus. The genome sequences are 16 653 bp in size, and the gene arrangement, composition, and size are very similar to the salmonid fish genomes published previously. The low level of sequence divergence detected between the genome of S. albus and the GenBank complete mitochondrial genomes of the Northern Dolly Varden char S. malma (KJ746618) and the Arctic char S. alpinus (AF154851) may likely be due to recent divergence of the species and/or historical hybridization and interspecific replacement of mtDNA. PMID- 26358826 TI - A survival tree method for the analysis of discrete event times in clinical and epidemiological studies. AB - Survival trees are a popular alternative to parametric survival modeling when there are interactions between the predictor variables or when the aim is to stratify patients into prognostic subgroups. A limitation of classical survival tree methodology is that most algorithms for tree construction are designed for continuous outcome variables. Hence, classical methods might not be appropriate if failure time data are measured on a discrete time scale (as is often the case in longitudinal studies where data are collected, e.g., quarterly or yearly). To address this issue, we develop a method for discrete survival tree construction. The proposed technique is based on the result that the likelihood of a discrete survival model is equivalent to the likelihood of a regression model for binary outcome data. Hence, we modify tree construction methods for binary outcomes such that they result in optimized partitions for the estimation of discrete hazard functions. By applying the proposed method to data from a randomized trial in patients with filarial lymphedema, we demonstrate how discrete survival trees can be used to identify clinically relevant patient groups with similar survival behavior. PMID- 26358828 TI - Coexistence of diode-like volatile and multilevel nonvolatile resistive switching in a ZrO2/TiO2 stack structure. AB - Diode-like volatile resistive switching as well as nonvolatile resistive switching behaviors in a Cu/ZrO2/TiO2/Ti stack are investigated. Depending on the current compliance during the electroforming process, either volatile resistive switching or nonvolatile resistive switching is observed. With a lower current compliance (<10 MUA), the Cu/ZrO2/TiO2/Ti device exhibits diode-like volatile resistive switching with a rectifying ratio over 10(6). The permanent transition from volatile to nonvolatile resistive switching can be obtained by applying a higher current compliance of 100 MUA. Furthermore, by using different reset voltages, the Cu/ZrO2/TiO2/Ti device exhibits multilevel memory characteristics with high uniformity. The coexistence of nonvolatile multilevel memory and diode like volatile resistive switching behaviors in the same Cu/ZrO2/TiO2/Ti device opens areas of applications in high-density storage, logic circuits, neural networks, and passive crossbar memory selectors. PMID- 26358827 TI - Non-Classical monocytes display inflammatory features: Validation in Sepsis and Systemic Lupus Erythematous. AB - Given the importance of monocytes in pathogenesis of infectious and other inflammatory disorders, delineating functional and phenotypic characterization of monocyte subsets has emerged as a critical requirement. Although human monocytes have been subdivided into three different populations based on surface expression of CD14 and CD16, published reports suffer from contradictions with respect to subset phenotypes and function. This has been attributed to discrepancies in reliable gating strategies for flow cytometric characterization and purification protocols contributing to significant changes in receptor expression. By using a combination of multicolour flow cytometry and a high-dimensional automated clustering algorithm to confirm robustness of gating strategy and analysis of ex vivo activation of whole blood with LPS we demonstrate the following: a. 'Classical' monocytes are phagocytic with no inflammatory attributes, b. 'Non classical' subtype display 'inflammatory' characteristics on activation and display properties for antigen presentation and c. 'Intermediate' subtype that constitutes a very small percentage in circulation (under physiological conditions) appear to be transitional monocytes that display both phagocytic and inflammatory function. Analysis of blood from patients with Sepsis, a pathogen driven acute inflammatory disease and Systemic Lupus Erythmatosus (SLE), a chronic inflammatory disorder validated the broad conclusions drawn in the study. PMID- 26358829 TI - Circulating 25-hydroxyvitamin D and risk of lung cancer: a dose-response meta analysis. AB - BACKGROUND: Mounting experimental evidence supports a protective effect of high 25-hydroxyvitamin D (25[OH]D), a good indicator of vitamin D status, on risk of various cancers including lung cancer. However, prospective observational studies examining the 25(OH)D-lung cancer association reported inconsistent findings. A dose-response meta-analysis was carried out to elucidate the subject. METHODS: Potentially eligible studies were identified by searching PubMed and EMBASE databases, and by carefully reviewing the bibliographies of retrieved publications. The summary relative risks (RRs) with 95% confidence intervals (CIs) were calculated using the random-effects model. RESULTS: Thirteen reports from ten prospective studies were included, totaling 2,227 lung cancer events. Results of the meta-analysis showed a significant 5% (RR 0.95, 95% CI 0.91-0.99) reduction in the risk of lung cancer for each 10 nmol/L increment in 25(OH)D concentrations. This inverse association was not significantly modified by area, study duration, sex, methods for 25(OH)D measurement, baseline 25(OH)D levels, or quality score of included studies. There was evidence of a nonlinear relationship between 25(OH)D and risk of lung cancer (p-nonlinearity = 0.02), with the greatest reductions in risk observed at 25(OH)D of nearly 53 nmol/L, and remained protective until approximately 90 nmol/L. Further increases showed no significant association with cancer risk, but scanty data were included in the analyses of high-level 25(OH)D. There was no evidence of publication bias. CONCLUSION: This dose-response meta-analysis of prospective studies suggests that 25(OH)D may be associated with reduced risk of lung cancer, in particular among subjects with vitamin D deficiencies. PMID- 26358830 TI - Excess body weight and colorectal cancer survival: the multiethnic cohort. AB - PURPOSE: Excess body weight is a risk factor for colorectal cancer (CRC) and may also adversely affect survival in CRC patients. METHODS: This study examined the relation of body mass index (BMI), which was self-reported at cohort entry and after 5.7 +/- 0.8 years, with CRC-specific and all-cause survival among 4,204 incident cases of invasive CRC in the multiethnic cohort. Cox regression analysis with age as time metric and BMI as time-varying exposure was applied to estimate hazard ratios (HR) and 95% confidence intervals (CIs) while adjusting for relevant covariates. RESULTS: Over 6.0 +/- 4.7 years of follow-up, 1,976 all cause and 1,095 CRC-specific deaths were recorded. The mean time interval between cohort entry and diagnosis was 7.6 +/- 4.7 years. No association with CRC specific survival was detected in men (HR5units = 0.94; 95%CI 0.84-1.04) or women (HR5units = 0.98; 95%CI 0.89-1.08). In men, all-cause survival also showed no relation with BMI (HR5unit = 0.97; 95%CI 0.90-1.06), whereas it was reduced in women (HR5units = 1.10; 95%CI 1.03-1.18). Interactions of BMI with ethnicity were only significant for obesity. Obese Latino and overweight Native Hawaiian men as well as overweight African-American women experienced significantly better CRC specific survival than whites. Overweight Japanese men and African-American women had better all-cause survival and obese Latino women had the lowest all-cause survival (HRobese = 1.74; 95%CI 1.08-2.80). CONCLUSIONS: This analysis detected little evidence for an adverse effect of excess body weight on CRC-specific survival, but all-cause survival was reduced in women. These findings suggest that adiposity may be less important for CRC survival than as an etiologic factor. PMID- 26358831 TI - Analysis of steroidogenic pathway key transcripts in interrenal cells isolated by laser microdissection (LMD) in stressed rainbow trout. AB - An assessment of the key transcripts expression of the steroidogenesis-related genes in rainbow trout subjected to either acute or chronic stress was performed in both interrenal cells and whole head kidney tissue. The analysis of interrenal cells was possible thanks to the use, for the first time in this specific type of cells, of the technique of laser microdissection (LMD) which allows to isolate specific cells and process them independently of other surrounding cells in the tissue. The results indicated that both acute and chronic stressors induced a significant up-regulation of the steroidogenesis-related genes with a higher but expected degree in the isolated cells. In addition, under acute stress a delay between cortisol levels and transcript expression was found. Under chronic stress a clear relation between plasma cortisol levels, mRNA transcription and interrenal tissue area was observed, since all parameters were concomitantly increased at day 5 after stress. Moreover results indicated that the LMD technique allowed ascertaining with more precision and accuracy whether and when the steroidogenesis-related genes were significantly expressed, disregarding the noise produced by other cells present in the head kidney. Results also showed a typical physiological response in plasma parameters and a positive relationship between plasma cortisol data and transcript abundance in isolated cells. The present results may help to better understand the mechanisms behind the interrenal response to stress challenges in fish. PMID- 26358832 TI - Fasting for 21days leads to changes in adipose tissue and liver physiology in juvenile checkered garter snakes (Thamnophis marcianus). AB - Snakes often undergo periods of prolonged fasting and, under certain conditions, can survive years without food. Despite this unique phenomenon, there are relatively few reports of the physiological adaptations to fasting in snakes. At post-prandial day 1 (fed) or 21 (fasting), brain, liver, and adipose tissues were collected from juvenile checkered garter snakes (Thamnophis marcianus). There was greater glycerol-3-phosphate dehydrogenase (G3PDH)-specific activity in the liver of fasted than fed snakes (P=0.01). The mRNA abundance of various fat metabolism associated factors was measured in brain, liver, and adipose tissue. Lipoprotein lipase (LPL) mRNA was greater in fasted than fed snakes in the brain (P=0.04). Adipose triglyceride lipase (ATGL; P=0.006) mRNA was greater in the liver of fasted than fed snakes. In adipose tissue, expression of peroxisome proliferator activated receptor (PPAR)gamma (P=0.01), and fatty acid binding protein 4 (P=0.03) was greater in fed than fasted snakes. Analysis of adipocyte morphology revealed that cross-sectional area (P=0.095) and diameter (P=0.27) were not significantly different between fed and fasted snakes. Results suggest that mean adipocyte area can be preserved during fasting by dampening lipid biosynthesis while not changing rates of lipid hydrolysis. In the liver, however, extensive lipid remodeling may provide energy and lipoproteins to maintain lipid structural integrity during energy restriction. Because the duration of fasting was not sufficient to change adipocyte size, results suggest that the liver is important as a short-term provider of energy in the snake. PMID- 26358833 TI - The investigation of systolic and diastolic leaflet kinematics of bioprostheses with a new in-vitro test method. AB - OBJECTIVES: We aimed to investigate leaflet kinematics of bioprostheses with a novel high-speed imaging method. MATERIAL AND METHODS: High-speed-imaging (1000 Hz) was used to evaluate leaflet kinematics of the Carpentier-Edwards Perimount Magna (PM) and Magna Ease (PME) aortic bioprostheses. Both prostheses (diameter 23 mm) were placed inside a model aorta under pulsatile flow conditions. Frequencies (F) and different stroke volumes (S) were simulated. Maximum aortic valve area (AVA), total ejection time (TET), rapid valve opening time (RVOT) and rapid valve closing time (RVCT) as well as opening (OS) and closing (CS) speeds were evaluated. RESULTS: Both bioprostheses showed different results dependent on flow conditions. The test setup was capable of identifying small AVA-differences between both valves (235 vs. 202 mm2, F60/S60; 272 vs. 207 mm2; F70/S80), as well as differences in OS and CS (2.36 vs. 1.62 mm2/ms; 2.97 vs. 2.44 mm2/ms, F80/S60). TET was comparable (638 vs. 645 ms F60/S60; 341 vs. 343 ms, F90/S60), while results for RVOT and RVCT were equal, and dependent on frequency and stroke volume. CONCLUSIONS: The novel evaluation method is sensitive to detect differences between valves, although differences were found to be small. PM has a larger visible AVA associated with higher opening and closing speeds in contrast to PME. PMID- 26358834 TI - Left subclavian artery rerouting and selective perfusion management in frozen elephant trunk surgery. AB - INTRODUCTION: The frozen elephant trunk (FET) technique enables combined aortic arch and descending aortic repair. We report our experience with a modified arch replacement technique by rerouting of the left subclavian artery (LSA) and fixation of the FET in Zone 2 or proximally under selective perfusion of all three arch arteries and the downstream aorta. MATERIAL AND METHODS: From January 2005 to December 2014, 78 of 173 patients operated with the FET technique underwent rerouting of the LSA. Rerouting was performed as aortic-subclavian, aorto-axillary or carotid-subclavia bypass. Hypothermic selective antegrade cerebral perfusion was established for cerebral protection. A separate cardiopulmonary bypass circuit was added for selective LSA and downstream aorta perfusion during the arch repair. RESULTS: In-hospital mortality, stroke and paraplegia rates were 10%, 8% and 2.5%, respectively. LSA rerouting enabled total arch repair in <60 minutes of selective cerebral perfusion (mean 56 +/- 15). No recurrent nerve palsy occurred. The selective perfusion of the downstream aorta led to the reduction of the distal hypothermic circulatory arrest time close to 30 minutes (p < 0.0001). DISCUSSION: LSA rerouting facilitates arch aortic repair by FET surgery. The selective perfusion of all arch arteries and the downstream aorta during open arch repair reduces the ischemic times and may improve organ protection. PMID- 26358835 TI - Tunable Valley Polarization and Valley Orbital Magnetic Moment Hall Effect in Honeycomb Systems with Broken Inversion Symmetry. AB - In this Letter, a tunable valley polarization is investigated for honeycomb systems with broken inversion symmetry such as transition-metal dichalcogenide MX2 (M = Mo, W; X = S, Se) monolayers through elliptical pumping. Compared to circular pumping, elliptical pumping is a more universal and effective method to create coherent valley polarization. When two valleys of MX2 monolayers are doped or polarized, a novel anomalous Hall effect (called valley orbital magnetic moment Hall effect) is predicted. Valley orbital magnetic moment Hall effect can generate an orbital magnetic moment current without the accompaniment of a charge current, which opens a new avenue for exploration of valleytronics and orbitronics. Valley orbital magnetic moment Hall effect is expected to overshadow spin Hall effect and is tunable under elliptical pumping. PMID- 26358836 TI - Additional deleterious effects of alcohol consumption on sperm parameters and DNA integrity in diabetic mice. AB - The aim of this study was to survey the impact of alcohol consumption on sperm parameters and DNA integrity in experimentally induced diabetic mice. A total of 32 adult male mice were divided into four groups: mice of group 1 served as control fed on basal diet, group 2 received streptozotocin (STZ) (200 mg kg(-1) , single dose, intraperitoneal) and basal diet, group 3 received alcohol (10 mg kg( 1) , water soluble) and basal diet, and group 4 received STZ and alcohol for 35 days. The cauda epididymidis of each mouse was dissected and placed in 1 ml of pre-warm Ham's F10 culture medium for 30 min. The swim-out spermatozoa were analysed for count, motility, morphology and viability. Sperm chromatin quality was evaluated with aniline blue, toluidine blue, acridine orange and chromomycin A3 staining. The results showed that all sperm parameters had significant differences (P < 0.05), also when sperm chromatin was assessed with cytochemical tests. There were significant differences (P < 0.001) between the groups. According to our results, alcohol and diabetes can cause abnormalities in sperm parameters and chromatin quality. In addition, alcohol consumption in diabetic mice can intensify sperm chromatin/DNA damage. PMID- 26358837 TI - Extremely high efficient nanoreactor with Au@ZnO catalyst for photocatalysis. AB - We fabricated a photocatalytic Au@ZnO@PC (polycarbonate) nanoreactor composed of monolayered Au nanoparticles chemisorbed on conformal ZnO nanochannel arrays within the PC membrane. A commercial PC membrane was used as the template for deposition of a ZnO shell into the pores by atomic layer deposition (ALD). Thioctic acid (TA) with sufficient steric stabilization was used as a molecular linker for functionalization of Au nanoparticles in a diameter of 10 nm. High coverage of Au nanoparticles anchored on the inner wall of ZnO nanochannels greatly improved the photocatalytic activity for degradation of Rhodamine B. The membrane nanoreactor achieved 63% degradation of Rhodamine B within only 26.88 ms of effective reaction time owing to its superior mass transfer efficiency based on Damkohler number analysis. Mass transfer limitation can be eliminated in the present study due to extremely large surface-to-volume ratio of the membrane nanoreactor. PMID- 26358838 TI - Stomaching Notch. PMID- 26358839 TI - Analysis of acetylation stoichiometry suggests that SIRT3 repairs nonenzymatic acetylation lesions. AB - Acetylation is frequently detected on mitochondrial enzymes, and the sirtuin deacetylase SIRT3 is thought to regulate metabolism by deacetylating mitochondrial proteins. However, the stoichiometry of acetylation has not been studied and is important for understanding whether SIRT3 regulates or suppresses acetylation. Using quantitative mass spectrometry, we measured acetylation stoichiometry in mouse liver tissue and found that SIRT3 suppressed acetylation to a very low stoichiometry at its target sites. By examining acetylation changes in the liver, heart, brain, and brown adipose tissue of fasted mice, we found that SIRT3-targeted sites were mostly unaffected by fasting, a dietary manipulation that is thought to regulate metabolism through SIRT3-dependent deacetylation. Globally increased mitochondrial acetylation in fasted liver tissue, higher stoichiometry at mitochondrial acetylation sites, and greater sensitivity of SIRT3-targeted sites to chemical acetylation in vitro and fasting induced acetylation in vivo, suggest a nonenzymatic mechanism of acetylation. Our data indicate that most mitochondrial acetylation occurs as a low-level nonenzymatic protein lesion and that SIRT3 functions as a protein repair factor that removes acetylation lesions from lysine residues. PMID- 26358840 TI - 13C metabolic flux analysis at a genome-scale. AB - Metabolic models used in 13C metabolic flux analysis generally include a limited number of reactions primarily from central metabolism. They typically omit degradation pathways, complete cofactor balances, and atom transition contributions for reactions outside central metabolism. This study addresses the impact on prediction fidelity of scaling-up mapping models to a genome-scale. The core mapping model employed in this study accounts for (75 reactions and 65 metabolites) primarily from central metabolism. The genome-scale metabolic mapping model (GSMM) (697 reaction and 595 metabolites) is constructed using as a basis the iAF1260 model upon eliminating reactions guaranteed not to carry flux based on growth and fermentation data for a minimal glucose growth medium. Labeling data for 17 amino acid fragments obtained from cells fed with glucose labeled at the second carbon was used to obtain fluxes and ranges. Metabolic fluxes and confidence intervals are estimated, for both core and genome-scale mapping models, by minimizing the sum of square of differences between predicted and experimentally measured labeling patterns using the EMU decomposition algorithm. Overall, we find that both topology and estimated values of the metabolic fluxes remain largely consistent between core and GSM model. Stepping up to a genome-scale mapping model leads to wider flux inference ranges for 20 key reactions present in the core model. The glycolysis flux range doubles due to the possibility of active gluconeogenesis, the TCA flux range expanded by 80% due to the availability of a bypass through arginine consistent with labeling data, and the transhydrogenase reaction flux was essentially unresolved due to the presence of as many as five routes for the inter-conversion of NADPH to NADH afforded by the genome-scale model. By globally accounting for ATP demands in the GSMM model the unused ATP decreased drastically with the lower bound matching the maintenance ATP requirement. A non-zero flux for the arginine degradation pathway was identified to meet biomass precursor demands as detailed in the iAF1260 model. Inferred ranges for 81% of the reactions in the genome-scale metabolic (GSM) model varied less than one-tenth of the basis glucose uptake rate (95% confidence test). This is because as many as 411 reactions in the GSM are growth coupled meaning that the single measurement of biomass formation rate locks the reaction flux values. This implies that accurate biomass formation rate and composition are critical for resolving metabolic fluxes away from central metabolism and suggests the importance of biomass composition (re)assessment under different genetic and environmental backgrounds. In addition, the loss of information associated with mapping fluxes from MFA on a core model to a GSM model is quantified. PMID- 26358841 TI - Efficacy and safety of olokizumab in Asian patients with moderate-to-severe rheumatoid arthritis, previously exposed to anti-TNF therapy: Results from a randomized phase II trial. AB - OBJECTIVES: This phase II, dose-ranging, double-blind, placebo-controlled, randomized study (NCT01463059) evaluated efficacy and safety of olokizumab (OKZ), a humanized anti-interleukin 6 monoclonal antibody, in Asian patients with moderately-to-severely active rheumatoid arthritis (RA) who had previously failed anti-TNF therapy. METHODS: Patients were randomized to one of six treatment arms: placebo or OKZ (60 mg/120 mg/240 mg every four weeks [Q4W]; or 60 mg/120 mg every two weeks [Q2W]); stratified by country and number of prior anti-TNFs. Primary efficacy variable was Week 12 change from baseline (CFB) in DAS28 CRP for 4-week cumulative dose groups of OKZ and placebo; secondary efficacy variables were Week 12 ACR20/ACR50/ACR70 response rates. Patients continued MTX treatment from baseline, without additional csDMARDs. RESULTS: Of 119 randomized patients, 88.2% completed the study. Greater improvements in DAS28(CRP) mean CFB at Week 12 were observed in all OKZ 4-week cumulative dose groups (60 mg/120 mg/240 mg) versus placebo (p < 0.0001). Week 12 ACR20/ACR50 response rates were higher in all OKZ cumulative dose groups versus PBO (p < 0.05). Incidences of adverse events were similar across OKZ 4-week cumulative dose groups (76.9-84.4%) and placebo (82.8%) with no deaths. CONCLUSIONS: OKZ demonstrated improvements in efficacy variables versus placebo in Asian patients with moderately-to-severely active RA who had previously failed anti-TNF therapy. The safety profile was as expected for this class of drug. PMID- 26358843 TI - Can skin disease cause neuropathic pain? A study in pachyonychia congenita. AB - INTRODUCTION: Pachyonychia congenita (PC) is a rare skin disorder caused by an autosomal dominant mutation in one of five genes encoding keratin (K6a, K6b, K6c, K16 or K17; each defining one PC subtype). Pain is a prominent symptom, but its severity and type are poorly characterized. METHODS: In total, 35 genotyped US patients with PC consented to clinical assessment including the quality of life (QoL) questionnaire EQ-5D-3L, the Brief Pain Inventory (BPI) and painDETECT. Abbreviated quantitative sensory testing (QST) was also performed, and included mechanical detection threshold (MDT), mechanical pain threshold (MPT), wind-up pain ratio (WUR) and vibration detection threshold (VDT). RESULTS: Significant pain in patients with PC was confirmed, as indicated by mean BPI severity and interference of 4.2 +/- 1.7 and 4.4 +/- 2.2, respectively, as well as QoL impairment, as indicated by mean EQ-5D index of 0.69 +/- 0.18. PD identified neuropathic pain in 62% of patients, the remainder being nociceptive. The painDETECT score was most significantly related to EQ-5D index (R(2) = 0.26, P = 0.02). The K17 and K6a subtypes exhibited significantly worse QoL (0.584 and 0.613 respectively) than the K16 and K6b subtypes (P = 0.02). In QST analysis, abnormal pressure pain (assessed as MPT) was frequently observed, with more than half of patients with PC affected (54%), and 57% of patients with K17 also exhibiting abnormality in minimum touch threshold (assessed as MDT, P < 0.05). Very few patients were receiving analgesic therapy appropriate for neuropathic pain. CONCLUSION: Significant neuropathic pain was observed in PC, which warrants appropriate treatment. The health states observed in this sample are at a level that the average US citizen would forfeit one-third of their remaining lifespan to avoid. PMID- 26358842 TI - In-depth proteomic analysis of Varroa destructor: Detection of DWV-complex, ABPV, VdMLV and honeybee proteins in the mite. AB - We investigated pathogens in the parasitic honeybee mite Varroa destructor using nanoLC-MS/MS (TripleTOF) and 2D-E-MS/MS proteomics approaches supplemented with affinity-chromatography to concentrate trace target proteins. Peptides were detected from the currently uncharacterized Varroa destructor Macula-like virus (VdMLV), the deformed wing virus (DWV)-complex and the acute bee paralysis virus (ABPV). Peptide alignments revealed detection of complete structural DWV-complex block VP2-VP1-VP3, VDV-1 helicase and single-amino-acid substitution A/K/Q in VP1, the ABPV structural block VP1-VP4-VP2-VP3 including uncleaved VP4/VP2, and VdMLV coat protein. Isoforms of viral structural proteins of highest abundance were localized via 2D-E. The presence of all types of capsid/coat proteins of a particular virus suggested the presence of virions in Varroa. Also, matches between the MWs of viral structural proteins on 2D-E and their theoretical MWs indicated that viruses were not digested. The absence/scarce detection of non structural proteins compared with high-abundance structural proteins suggest that the viruses did not replicate in the mite; hence, virions accumulate in the Varroa gut via hemolymph feeding. Hemolymph feeding also resulted in the detection of a variety of honeybee proteins. The advantages of MS-based proteomics for pathogen detection, false-positive pathogen detection, virus replication, posttranslational modifications, and the presence of honeybee proteins in Varroa are discussed. PMID- 26358844 TI - Clinical classification and medical treatment options in childhood glaucoma. PMID- 26358845 TI - Locating Gases in Porous Materials: Cryogenic Loading of Fuel-Related Gases Into a Sc-based Metal-Organic Framework under Extreme Pressures. AB - An alternative approach to loading metal organic frameworks with gas molecules at high (kbar) pressures is reported. The technique, which uses liquefied gases as pressure transmitting media within a diamond anvil cell along with a single crystal of a porous metal-organic framework, is demonstrated to have considerable advantages over other gas-loading methods when investigating host-guest interactions. Specifically, loading the metal-organic framework Sc2BDC3 with liquefied CO2 at 2 kbar reveals the presence of three adsorption sites, one previously unreported, and resolves previous inconsistencies between structural data and adsorption isotherms. A further study with supercritical CH4 at 3-25 kbar demonstrates hyperfilling of the Sc2 BDC3 and two high-pressure displacive and reversible phase transitions are induced as the filled MOF adapts to reduce the volume of the system. PMID- 26358846 TI - Platelet Activating Factor (PAF) biosynthesis is inhibited by phenolic compounds in U-937 cells under inflammatory conditions. AB - Interleukin 1 beta (IL-1beta) induced platelet activating factor (PAF) synthesis in U-937 cells through stimulation of acetyl-CoA:lysoPAF-acetyltransferase (lyso PAF-AT) at 3 h and DTT-independentCDP-choline-1-alkyl-2-acetyl-sn-glycerol cholinophosphotransferase (PAF-CPT) at 0.5 h. The aim of this study was to investigate the effect of tyrosol (T), resveratrol (R) and their acetylated derivatives(AcDs) which exhibit enhanced bioavailability, on PAF synthesis in U 937 after IL-1beta stimulation. The specific activity of PAF enzymes and intracellular levels were measured in cell homogenates. T and R concentration capable of inducing 50% inhibition in IL-1beta effect on lyso PAF-AT was 48 MUMU +/- 11 and 157 MUMU +/- 77, for PAF-CPT 246 MUMU +/- 61 and 294 MUMU +/- 102, respectively. The same order of concentration was also observed on inhibiting PAF levels produced by IL-1beta. T was more potent inhibitor than R (p<0.05). AcDs of T retain parent compound inhibitory activity, while in the case of R only two AcDs retain the activity. The observed inhibitory effect by T,R and their AcDs, may partly explain their already reported beneficial role. PMID- 26358847 TI - Clinical pathway to discharge three days after colorectal endoscopic submucosal dissection: For whom and for what purpose? PMID- 26358849 TI - Photosystem I cyclic electron flow via chloroplast NADH dehydrogenase-like complex performs a physiological role for photosynthesis at low light. AB - Cyclic electron transport around photosystem I (PS I) was discovered more than a half-century ago and two pathways have been identified in angiosperms. Although substantial progress has been made in understanding the structure of the chloroplast NADH dehydrogenase-like (NDH) complex, which mediates one route of the cyclic electron transport pathways, its physiological function is not well understood. Most studies focused on the role of the NDH-dependent PS I cyclic electron transport in alleviation of oxidative damage in strong light. In contrast, here it is shown that impairment of NDH-dependent cyclic electron flow in rice specifically causes a reduction in the electron transport rate through PS I (ETR I) at low light intensity with a concomitant reduction in CO2 assimilation rate, plant biomass and importantly, grain production. There was no effect on PS II function at low or high light intensity. We propose a significant physiological function for the chloroplast NDH at low light intensities commonly experienced during the reproductive and ripening stages of rice cultivation that have adverse effects crop yield. PMID- 26358850 TI - The impact of electronic medication administration records in a residential aged care home. AB - PURPOSES: This study aimed to compare between electronic medication administration records and paper-based records in the nursing time spent on various activities in a medication round and the medication administration processes followed by nurses in an Australian residential aged care home. It also aimed to identify the benefits and unintended adverse consequences of using the electronic medication administration records. METHODS: Time-motion observation, taking of field notes, informal conversation and document review were used to collect data in two units of a residential aged care home. Each unit had one nurse administer medication. Seven nurses were observed over 12 morning shifts. Unit 1 used electronic medication administration records and Unit 2 used paper based records. RESULTS: No significant difference between the two units was found in the nursing time spent on various activities in a medication round, including documentation, verbal communication, medication administration, infection control and transit. Comparison of the medication administration processes between the electronic and paper-based medication administration records identified a procedural problem which violated the organization's documentation requirement. This problem was documenting before providing medication to a resident when using the paper-based records. It was not observed with the electronic medication administration records. Benefits of introducing the electronic medication administration records included improving nurses' compliance with documentation requirements, freedom from the error of signing twice, reducing the possibility of forgetting to medicate a resident, facilitating nurses to record the time of medication administration to a resident and increasing documentation space. Unintended adverse consequences of introducing the electronic medication administration records included inadequate information about residents, late addition of a new resident's medication profile in the records and nurses' forgetting to medicate a resident due to power outage of the portable device. CONCLUSIONS: The electronic medication administration records may not change nursing time spent on various activities in a medication round or substantially alter the medication administration processes, but can generate both benefits and unintended adverse consequences. Future research may investigate whether and how the adverse consequences can be prevented. PMID- 26358851 TI - Contribution of M470V variant to cystic fibrosis: First study in CF and normal Tunisian population. AB - PURPOSE: Determining the frequency of M470V polymorphism in cystic fibrosis and healthy cohort in Tunisia to establish the contribution of M470V polymorphism in cystic fibrosis variable presentation and course. Additionally, studying the origin of cystic fibrosis transmembrane conductance regulator gene in Tunisian population and its evolution among populations worldwide. PATIENTS AND METHODS: The genotyping of M470V marker was realized by PCR-RFLP technique in 34 unrelated patients and 50 healthy subjects. RESULTS: Statistical difference was found in the genotype and allelic distribution between CF and control groups. Exclusive association between F508del allele and M470 allele was noted. CONCLUSION: This study has contributed to better understanding involvement of the M470V polymorphism in the CF clinical expression in the Tunisian population and has confirmed the utility of this marker in the study of the origin and evolution of the CFTR locus in the human history. PMID- 26358853 TI - Exclusive pi Encapsulation of Light Alkali Metal Cations by a Neutral Molecule. AB - Cation-pi interactions are one of the most important classes of noncovalent bonding, and are seen throughout biology, chemistry, and materials science. However, in almost every documented case, these interactions play only a supporting role to much stronger covalent or dative bonds, thus making examples of exclusive cation-pi bonding exceedingly rare. In this study, a neutral diboryne molecule is found to encapsulate the light alkali metal cations Li(+) and Na(+) in the absence of a net charge, covalent bonds, or lone-pair donor groups. The resulting encapsulation complexes are, to our knowledge, the first structurally authenticated species in which a neutral molecule binds the light alkali metals exclusively through cation-pi interactions. PMID- 26358852 TI - Altered expression of histone deacetylases, inflammatory cytokines and contractile-associated factors in uterine myometrium of Long Evans rats gestationally exposed to benzo[a]pyrene. AB - Etiology of preterm birth (PTB) is multifactorial; therefore, decreasing the incidence of PTB is a major challenge in the field of obstetrics. Epidemiological studies have reported an association between toxicants and PTB. However, there are no studies on the role of benzo[a]pyrene (BaP), an environmental toxicant, in the incidence of PTB. We first assessed the effects of BaP (150 and 300 ug kg(-1) body weight) dosed via gavage from day 14 to 17 of pregnancy on gestation length in Long Evans rats. We further assessed the histopathology of the uterus, expression of inflammatory cytokines, contractile-associated factors, histone deacetylases (HDACs) and NF?B-p65 in myometrium collected on day 22 postpartum versus vehicle-treated controls. In our study, rats exposed to BaP delivered prematurely (P < 0.05) compared to control. Hematoxylin and eosin staining of uterus showed squamous metaplasia, glandular and stromal hyperplasia in BaP exposed rats versus control. The concentrations of BaP metabolites measured by high-pressure liquid chromatography were higher in uterine myometrium of BaP exposed rats while they were undetectable in controls. Quantitative real-time polymerase chain reaction showed significant increases in mRNA expression of interleukin-1beta and -8, tumor necrosis factor-alpha, connexin 43, cyclo oxygenase-2 and prostaglandin F2alpha receptor as compared to controls (P < 0.05). Western blot analysis revealed that BaP exposure caused decreases in class I HDACs 1 and 3 and increases in class II HDAC 5, cyclo-oxygenase-2 and nuclear translocation of NFkappaB-p65 relative to controls. Our results suggest that gestational exposure to BaP increases incidence of PTB through epigenetic changes that causes increases in the expression of contractile-associated factors through the NFkappaB pathway. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26358854 TI - How to be good at being bad: centrosome amplification and mitotic propensity drive intratumoral heterogeneity. AB - Cancer is truly an iconic disease--a tour de force whose multiple formidable strengths can be attributed to the bewildering heterogeneity that a tumor can manifest both spatially and temporally. A Darwinian evolutionary process is believed to undergird, at least in part, the generation of this heterogeneity that contributes to poor clinical outcomes. Risk assessment in clinical oncology is currently based on a small number of clinicopathologic factors (like stage, histological grade, receptor status, and serum tumor markers) and offers limited accuracy in predicting disease course as evidenced by the prognostic heterogeneity that persists in risk segments produced by present-day models. We posit that this insufficiency stems from the exclusion of key risk contributors from such models, especially the omission of certain factors implicated in generating intratumoral heterogeneity. The extent of centrosome amplification and the mitotic propensity inherent in a tumor are two such vital factors whose contributions to poor prognosis are presently overlooked in risk prognostication. Supernumerary centrosomes occur widely in tumors and are potent drivers of chromosomal instability that fosters intratumoral heterogeneity. The mitotic propensity of a proliferating population of tumor cells reflects the cell cycling kinetics of that population. Since frequent passage through improperly regulated mitotic divisions accelerates production of diverse genotypes, the mitotic propensity inherent in a tumor serves as a powerful beacon of risk. In this review, we highlight how centrosome amplification and error-prone mitoses contribute to poor clinical outcomes and urge the need to develop these cancer specific traits as much-needed clinically-facile prognostic biomarkers with immense potential value for individualized cancer treatment in the clinic. PMID- 26358855 TI - Severe bacterial infections in patients with non-transfusion-dependent thalassemia: prevalence and clinical risk factors. AB - INTRODUCTION: Bacterial infection is one of the major causes of death in patients with thalassemia. Clinical predictive factors for severe bacterial infection were evaluated in patients with non-transfusion-dependent thalassemia (NTDT). METHODS: A retrospective study was conducted of patients with NTDT aged >= 10 years at Srinagarind Hospital, Khon Kaen University, Thailand. Clinical characteristics and potential clinical risk factors for bacterial infection were collected. Risk factors for bacterial infection were evaluated by multivariate logistic regression analysis. RESULTS: A severe bacterial infection was found in 11 of the total 211 patients with NTDT (5.2%). None of the clinical factors assessed was shown to be statistically associated with severe bacterial infection in patients with NTDT. However, three factors were demonstrated to be potential predictive factors for severe bacterial infection: time after splenectomy >10 years, deferoxamine therapy, and serum ferritin >1000 ng/ml. None of the patients died from infection. CONCLUSION: The prevalence of bacterial infection in patients with NTDT was found to be moderate. Time after splenectomy >10 years, deferoxamine therapy, and iron overload may be clinical risk factors for severe bacterial infection in patients with NTDT. Bacterial infection should be recognized in splenectomized patients with NTDT, particularly those who have an iron overload. PMID- 26358856 TI - Predictors of mortality and treatment success during treatment for rifampicin resistant tuberculosis within the South African National TB Programme, 2009 to 2011: a cohort analysis of the national case register. AB - BACKGROUND: The South African Electronic Drug-Resistant Tuberculosis Register (EDRweb) is the national database of registered drug-resistant tuberculosis (DR TB) cases. METHODS: This study was a retrospective, de-identified secondary analysis of EDRweb patients initiating treatment for rifampicin-resistant TB (January 2009 to September 2011). The relative risks of death and treatment success were estimated using modified Poisson regression with robust error estimation. RESULTS: Seventeen thousand six hundred and ninety-seven cases of DR TB were registered and met the inclusion criteria; 52.0% (n=9207) were male and the median age was 35 years (interquartile range 27-43 years). Of the 9419 cases with HIV infection (53.2%), 7157 (76.0%) were on antiretroviral therapy. Most had undergone previous TB treatment (76.5%, n=13531). Multidrug-resistant TB was the most common diagnosis, at 80.6% (n=14272). No treatment outcome was available for 6934 patients (39.2%). For patients with outcomes, 4227 (39.4%) were successfully treated, 2987 (27.8%) died, 2533 (23.7%) were lost to follow-up, and 996 (9.3%) failed. Second-line drug resistance was the strongest predictor of death during DR-TB treatment; extensively drug-resistant TB patients were more likely to have died during treatment (adjusted relative risk 2.63, 95% confidence interval 2.45 2.84). CONCLUSIONS: Testing for second-line drug resistance at initiation of DR TB treatment can identify patients most at risk of treatment failure and death and most in need of individualized treatment. PMID- 26358857 TI - Immune profiling of the progression of a BALB/c mouse aerosol infection by Burkholderia pseudomallei and the therapeutic implications of targeting HMGB1. AB - INTRODUCTION: The role of damage-associated molecular pattern HMGB1 signalling in a murine BALB/c model of severe respiratory melioidosis (Burkholderia pseudomallei infection) was explored in this study. METHODS: Time course experiments were performed. RESULTS: It was established that HMGB1 was released in concert with increasing weight of organs and increasing concentration of liver enzymes in the blood a short time after cytokine release. Differences in the cytokine response between organs were observed, where the lungs contained higher concentrations of chemokines and interleukin 17, while the spleen produced more interferon-gamma, which is essential in the host defence against B. pseudomallei. This is evidence as to why the disease is seemingly more severe in the respiratory form. The effect of depleting HMGB1 using an antibody was also evaluated. It was found that this treatment significantly reduced bacterial load in the liver, spleen, and, to a greater degree, in the lungs. Cytokine quantification indicated that this reduction in bacterial load is likely due to the treatment reducing the release of a variety of pro-inflammatory cytokines. CONCLUSION: It is concluded that anti-HMGB1 treatment would be effective alongside other therapeutics, where it would reduce the characteristic over inflammation associated with late stage infection. PMID- 26358858 TI - Multicenter clinical evaluation of three commercial reagent kits based on the interferon-gamma release assay for the rapid diagnosis of tuberculosis in China. AB - OBJECTIVE: To evaluate the performance of three interferon-gamma release assay (IGRA) kits in detecting Mycobacterium tuberculosis infection in China. METHODS: A multicenter clinical trial was used to compare the effectiveness and application of the three kits. A total of 1026 participants were enrolled at three hospitals, including 597 tuberculosis (TB) patients diagnosed clinically (517 patients with pulmonary TB and 80 patients with extrapulmonary TB) and 429 negative controls (244 patients with pulmonary disease but not TB, or with non tuberculosis mycobacterial lung diseases, and 185 healthy people). Detection performance indicators including sensitivity, specificity, and the Youden index (YI) were used to evaluate performance. RESULTS: Through bacterial culture evaluation, 224 of the 517 pulmonary TB patients were positive and all 429 negative controls were negative. When the gold standard bacterial methods were used, the sensitivity, specificity, and YI were 89.7% (201/224), 91.1% (391/429), and 0.81 for T-SPOT.TB, 86.2% (193/224), 87.2% (374/429), and 0.73 for QB-SPOT, and 83.9% (188/224), 88.6% (380/429), and 0.73 for TB-IGRA, respectively. There were no significant differences in the sensitivity and specificity of the three kits. CONCLUSIONS: The results showed that the three kits had very high sensitivity and specificity and exhibited a good performance for the detection of M. tuberculosis infection. PMID- 26358859 TI - A systematic review and meta-analysis of the prevalence, trends, and geographical distribution of HIV among Chinese female sex workers (2000-2011): implications for preventing sexually transmitted HIV. AB - OBJECTIVE: The aim of this meta-analysis was to investigate temporal and geographical trends in the HIV epidemic among female sex workers (FSWs) recruited from various venues in China. METHODS: Chinese and English peer-reviewed articles published between January 2000 and February 2013 were systematically searched. Standard meta-analysis methods were used to calculate the pooled HIV prevalence, in accordance with the PRISMA guidelines. RESULTS: The national HIV prevalence among FSWs declined from 0.74% (95% confidence interval (CI) 0.37-1.49%) in 2000 2002 to 0.40% (95% CI 0.31-0.53%) in 2009-2011. All Chinese regions demonstrated significant declines in HIV prevalence, apart from the East and South Central regions, in which the epidemics stabilized at low/moderate levels. Despite a significant decline from 1.92% (95% CI 0.86-4.24%) to 0.87% (95% CI 0.65-1.18%) during 2000-2011, Southwest China still bore the greatest HIV disease burden. Nationwide, FSWs recruited from detention centres had the highest HIV prevalence (0.92%, 95% CI 0.46-1.88%), followed by voluntary counselling and testing sites (0.80%, 95% CI 0.46-1.67%) and entertainment venues (0.61%, 95% CI 0.47-0.79%). The prevalences among FSWs in high-, middle-, and low-tier entertainment venues were 0.59% (95% CI 0.32-1.45%), 0.92% (95% CI 0.50-1.77%), and 1.10% (95% CI 0.71 2.16%), respectively. High- and middle-tier FSWs had a significantly lower risk of HIV infection than lower-tier FSWs (high/low: odds ratio (OR) 0.48, 95% CI 0.40-0.59; middle/low: OR 0.49, 95% CI 0.37-0.66). CONCLUSIONS: The HIV epidemic has shown a gradual declining or stabilizing trend among Chinese FSWs. Intervention efforts should be diverted to high-risk subgroups of FSWs, such as drug-using and low-tier FSWs. PMID- 26358860 TI - Reversal of cardiomyopathy in propionic acidemia after liver transplantation: a 10-year follow-up. AB - Cardiomyopathy is a frequent complication in propionic acidemia. It is mostly rapidly fatal and independent of the metabolic control or medical intervention. Here, we present the reversal of a severe cardiomyopathy after liver transplantation in a patient with propionic acidemia and the long-term stability after ten years. Liver transplantation in patients with propionic acidemia may be considered a valid and long-lasting treatment when cardiomyopathy is progressive and unresponsive to medical therapy. PMID- 26358861 TI - Learning to distinguish between predators and non-predators: understanding the critical role of diet cues and predator odours in generalisation. AB - It is critical for prey to recognise predators and distinguish predators from non threatening species. Yet, we have little understanding of how prey develop effective predator recognition templates. Recent studies suggest that prey may actually learn key predator features which can be used to recognise novel species with similar characteristics. However, non-predators are sometimes mislabelled as predators when generalising recognition. Here, we conduct the first comprehensive investigation of how prey integrate information on predator odours and predator diet cues in generalisation, allowing them to discriminate between predators and non-predators. We taught lemon damselfish to recognise a predator fed a fish diet, and tested them for their response to the known predator and a series of novel predators (fed fish diet) and non-predators (fed squid diet) distributed across a phylogenetic gradient. Our findings show that damselfish distinguish between predators and non-predators when generalising recognition. Additional experiments revealed that generalised recognition did not result from recognition of predator odours or diet cues, but that damselfish based recognition on what they learned during the initial conditioning. Incorporating multiple sources of information enables prey to develop highly plastic and accurate recognition templates that will increase survival in patchy environments where they have little prior knowledge. PMID- 26358862 TI - WITHDRAWN: Comparative evaluation of two vaginal self-sampling devices for the detection of human papillomavirus infections. AB - This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy. PMID- 26358863 TI - Nurses' views on patient self-management: a qualitative study. AB - AIMS: To unravel outpatient nurses' views on the role of people with chronic conditions in self-management, nurses' own support role and to establish how these views relate to nurse-led self-management interventions. BACKGROUND: Providing self-management support is a core task of nurses in outpatient chronic care. However, the concept of self-management is interpreted in different ways and little is known about nurses' views on patients' role in self-management and nurses' own support role. DESIGN: Qualitative design. METHODS: Individual semi structured interviews were held in 2012-2013 with outpatient nurses at a university medical hospital in the Netherlands. After transcription, data-driven codes were assigned and key elements of views and experiences were discussed in the research team. Finally, insights were merged to construct and characterize types. RESULTS: Twenty-seven nurses were interviewed. The analysis identified three divergent views on self-management support: adhering to a medical regimen; monitoring symptoms; and integrating illness into daily life. These views differ with respect to the patient's role in self-management, the support role of the nurse and the focus of activities, ranging from biomedical to biopsychosocial. The first two were mainly medically oriented. Nurses applied interventions consistent with their individual views on self-management. CONCLUSION: Nurses had distinct perceptions about self-management and their own role in self-management support. Social and emotional tasks of living with a chronic condition were, however, overlooked. Nurses seem to lack sufficient training and practical interventions to provide self-management support that meets the integral needs of patients with a chronic condition. PMID- 26358864 TI - Early onset intellectual disability in chromosome 22q11.2 deletion syndrome. AB - Chromosome 22q11.2 deletion syndrome, or DiGeorge syndrome, or velocardiofacial syndrome, is one of the most common multiple anomaly syndromes in humans. This syndrome is commonly caused by a microdelection from chromosome 22 at band q11.2. Although this genetic disorder may reflect several clinical abnormalities and different degrees of organ commitment, the clinical features that have driven the greatest amount of attention are behavioral and developmental features, because individuals with 22q11.2 deletion syndrome have a 30-fold risk of developing schizophrenia. There are differing opinions about the cognitive development, and commonly a cognitive decline rather than an early onset intellectual disability has been observed. We report a case of 22q11.2 deletion syndrome with both early assessment of mild intellectual disabilities and tetralogy of Fallot as the only physic manifestation. PMID- 26358865 TI - Recent knowledge: Concepts of dermal absorption in relation to skin decontamination. AB - Skin decontamination is an important step mitigating percutaneous absorption through the stratum corneum (SC), which is also a highly complex process. Thus, understanding diffusion mechanisms and measuring dermal absorption rates are critical to protect humans from toxic exposures. Here, highly varied literature is placed in a biological and clinical perspective in regards to decontamination. Literature from PubMed and Surge Laboratory library files were searched and reviewed for relevance. Recent data have shown multiple layers of SC structural heterogeneity, which results in unique substance partitioning characteristics across the membrane. As such, attempts to model and understand this behavior in alternative in vitro membranes prove difficult. More synthetic and natural membranes are being explored as models for in vivo behavior. In addition, commonly accepted decontamination methods are undergoing risk assessment. These recent and varied literature findings update available knowledge regarding skin decontamination and its challenges, with a focus on dermal absorption. PMID- 26358866 TI - Hydroaminations of alkenes: a radical, revised, and expanded version. AB - Radical changes: The applicability of alkene hydroamination has recently been significantly expanded by the development of radical variants that are based on initial hydrogen atom transfer to the alkene. This Highlight assesses the current state of the art, focusing on an iron-catalyzed reaction that utilizes stable nitroarenes as the electrophilic N component and is based on the dual catalytic activation of both starting materials. PMID- 26358867 TI - Targeting Th17 Effector Cytokines for the Treatment of Autoimmune Diseases. AB - Interleukin (IL)-17-producing T cells, especially T helper (Th)17 cells, play a critical role in the pathogenesis of a variety of autoimmune inflammatory diseases. The pathogenic function of Th17 cells results from their production of Th17 effector cytokines, namely IL-17 (or IL-17A), IL-17F, IL-22 and IL-26. The importance of IL-17 has been demonstrated by antibody neutralization studies in both animal models of autoimmune diseases as well as in human clinical trials. This review highlights the current knowledge of the clinical aspects of the Th17 cytokines as well as therapeutic antibodies against IL-17, IL-17F, IL-17 receptor, IL-22, IL-26 and granulocyte macrophage colony-stimulating factor for the future treatment of autoimmune inflammatory diseases. PMID- 26358869 TI - The Maternal-to-Zygotic Transition in C. elegans. AB - In Caenorhabditis elegans, the first zygotic transcription can be detected in the 4-cell stage C. elegans embryo, a little over 2h after fertilization. However, early development until the onset of gastrulation at approximately the 28-cell stage takes place normally even in the absence of zygotic transcription. Therefore, posttranslational and posttranscriptional regulation of the maternal proteins and mRNAs, respectively, that are loaded into the developing oocytes is sufficient to direct development prior to gastrulation. Protein phosphorylation is extensively used throughout the C. elegans maternal-to-zygotic transition (MZT): (1) for maternal protein activation, (2) for coordination of the meiotic and mitotic cell cycle, (3) to mark specific proteins for degradation, and/or (4) to switch the biochemical activity of specific proteins. Maternally loaded mRNAs are regulated primarily by a set of maternal RNA-binding proteins (RBPs), each of which binds to sometimes overlapping target sequences within the mRNA 3'UTRs and either promotes or inhibits translation. Most maternal transcripts are uniformly distributed throughout the embryo but specific transcripts are translated only in certain blastomeres. This control is achieved by the asymmetric distribution of the maternal RBPs, such that the blastomere-specific constellation of RBPs present, and their relative levels, determines the translational readout for their target transcripts. In certain well-studied cases, such as the specification of the sole endodermal precursor in the 8-cell embryo, the maternal transcripts and proteins along with their directly targeted zygotic genes have been identified. PMID- 26358870 TI - Regulation and Function of Maternal Gene Products During the Maternal-to-Zygotic Transition in Drosophila. AB - Drosophila late-stage oocytes and early embryos are transcriptionally silent. Thus, control of gene expression during these developmental periods is posttranscriptional and posttranslational. Global changes in the transcriptome and proteome occur during oocyte maturation, after egg activation and fertilization, and upon zygotic genome activation. We review the scale, content, and dynamics of these global changes; the factors that regulate these changes; and the mechanisms by which they are accomplished. We highlight the intimate relationship between the clearance of maternal gene products and the activation of the embryo's own genome, and discuss the fact that each of these complementary components of the maternal-to-zygotic transition can be subdivided into several phases that serve different biological roles and are regulated by distinct factors. PMID- 26358868 TI - The Roles and Mechanisms of Actions of Vitamin C in Bone: New Developments. AB - Vitamin C is an important antioxidant and cofactor that is involved in the regulation of development, function, and maintenance of several cell types in the body. Deficiencies in vitamin C can lead to conditions such as scurvy, which, among other ailments, causes gingivia, bone pain, and impaired wound healing. This review examines the functional importance of vitamin C as it relates to the development and maintenance of bone tissues. Analysis of several epidemiological studies and genetic mouse models regarding the effect of vitamin C shows a positive effect on bone health. Overall, vitamin C exerts a positive effect on trabecular bone formation by influencing expression of bone matrix genes in osteoblasts. Recent studies on the molecular pathway for vitamin C actions that include direct effects of vitamin C on transcriptional regulation of target genes by influencing the activity of transcription factors and by epigenetic modification of key genes involved in skeletal development and maintenance are discussed. With an understanding of mechanisms involved in the uptake and metabolism of vitamin C and knowledge of precise molecular pathways for vitamin C actions in bone cells, it is possible that novel therapeutic strategies can be developed or existing therapies can be modified for the treatment of osteoporotic fractures. PMID- 26358871 TI - Transcriptional Activation of the Zygotic Genome in Drosophila. AB - During the first stages of metazoan development, the genomes of the highly specified sperm and egg must unite and be reprogrammed to allow for the generation of a new organism. This process is controlled by maternally deposited products. Initially, the zygotic genome is largely transcriptionally quiescent, and it is not until hours later that the zygotic genome takes control of development. The transcriptional activation of the zygotic genome is tightly coordinated with the degradation of the maternal products. Here, we review the current understanding of the processes that mediate the reprogramming of the early embryonic genome and facilitate transcriptional activation during the early stages of Drosophila development. PMID- 26358872 TI - Coordinating Cell Cycle Remodeling with Transcriptional Activation at the Drosophila MBT. AB - During the maternal-to-zygotic transition (MZT), major changes in cell cycle regulation coincide with large-scale zygotic genome activation. In this chapter, we discuss the current understanding of how the cell cycle is remodeled over the course of the Drosophila MZT, and how the temporal precision of this event is linked to contemporaneous alterations in genome-wide chromatin structure and transcriptional activity. The cell cycle is initially lengthened during the MZT by activation of the DNA replication checkpoint but, subsequently, zygotically supplied factors are essential for establishing lasting modifications to the cell cycle. PMID- 26358873 TI - Germ Line Versus Soma in the Transition from Egg to Embryo. AB - With few exceptions, all animals acquire the ability to produce eggs or sperm at some point in their life cycle. Despite this near-universal requirement for sexual reproduction, there exists an incredible diversity in germ line development. For example, animals exhibit a vast range of differences in the timing at which the germ line, which retains reproductive potential, separates from the soma, or terminally differentiated, nonreproductive cells. This separation may occur during embryonic development, after gastrulation, or even in adults, depending on the organism. The molecular mechanisms of germ line segregation are also highly diverse, and intimately intertwined with the overall transition from a fertilized egg to an embryo. The earliest embryonic stages of many species are largely controlled by maternally supplied factors. Later in development, patterning control shifts to the embryonic genome and, concomitantly with this transition, the maternally supplied factors are broadly degraded. This chapter attempts to integrate these processes--germ line segregation, and how the divergence of germ line and soma may utilize the egg to embryo transitions differently. In some embryos, this difference is subtle or maybe lacking altogether, whereas in other embryos, this difference in utilization may be a key step in the divergence of the two lineages. Here, we will focus our discussion on the echinoderms, and in particular the sea urchins, in which recent studies have provided mechanistic understanding in germ line determination. We propose that the germ line in sea urchins requires an acquisition of maternal factors from the egg and, when compared to other members of the taxon, this appears to be a derived mechanism. The acquisition is early--at the 32-cell stage--and involves active protection of maternal mRNAs, which are instead degraded in somatic cells with the maternal-to-embryonic transition. We collectively refer to this model as the Time Capsule method for germ line determination. PMID- 26358875 TI - Building the Future: Post-transcriptional Regulation of Cell Fate Decisions Prior to the Xenopus Midblastula Transition. AB - In all animals, a critical period in early development is when embryonic cells switch from relying solely upon maternally deposited RNAs and proteins to relying upon molecules encoded by the zygotic genome. Xenopus embryos have served as a model for examining this switch, as well as the maternally controlled stages that prepare for it. In Xenopus, the robust activation of zygotic transcription occurs at the 12th cleavage division and is referred to as the midblastula transition (MBT). Prior to MBT, gene expression is regulated by post-transcriptional events including mRNA and protein localization, protein post-translational modification, and mRNA translation. After the MBT, appropriate transcriptional regulation of the zygotic genome becomes critical and predominates. However, it is important to realize that the first key cell fate decisions that have profound impacts on development occur prior to the MBT and these are governed by regulating the expression of maternally deposited regulatory mRNAs and proteins. In this chapter, I will discuss post-transcriptional mechanisms that function during the maternal stages of Xenopus development with an emphasis on mechanisms known to directly modulate cell fate decisions. Emerging approaches and technologies that will help better understand this phase of development will also be discussed. PMID- 26358874 TI - The Maternal-to-Zygotic Transition During Vertebrate Development: A Model for Reprogramming. AB - Cellular transitions occur at all stages of organismal life from conception to adult regeneration. Changing cellular state involves three main features: activating gene expression necessary to install the new cellular state, modifying the chromatin status to stabilize the new gene expression program, and removing existing gene products to clear out the previous cellular program. The maternal to-zygotic transition (MZT) is one of the most profound changes in the life of an organism. It involves gene expression remodeling at all levels, including the active clearance of the maternal oocyte program to adopt the embryonic totipotency. In this chapter, we provide an overview of molecular mechanisms driving maternal mRNA clearance during the MZT, describe the developmental consequences of losing components of this gene regulation, and illustrate how remodeling of gene expression during the MZT is common to other cellular transitions with parallels to cellular reprogramming. PMID- 26358877 TI - Sculpting the Transcriptome During the Oocyte-to-Embryo Transition in Mouse. AB - In mouse, the oocyte-to-embryo transition entails converting a highly differentiated oocyte to totipotent blastomeres. This transition is driven by degradation of maternal mRNAs, which results in loss of oocyte identity, and reprogramming of gene expression during the course of zygotic gene activation, which occurs primarily during the two-cell stage and confers blastomere totipotency. Full-grown oocytes are transcriptionally quiescent and mRNAs are remarkably stable in oocytes due to the RNA-binding protein MSY2, which stabilizes mRNAs, and low activity of the 5' and 3' RNA degradation machinery. Oocyte maturation initiates a transition from mRNA stability to instability due to phosphorylation of MSY2, which makes mRNAs more susceptible to the RNA degradation machinery, and recruitment of dormant maternal mRNAs that encode for critical components of the 5' and 3' RNA degradation machinery. Small RNAs (miRNA, siRNA, and piRNA) play little, if any, role in mRNA degradation that occurs during maturation. Many mRNAs are totally degraded but a substantial fraction is only partially degraded, their degradation completed by the end of the two-cell stage. Genome activation initiates during the one-cell stage, is promiscuous, low level, and genome wide (and includes both inter- and intragenic regions) and produces transcripts that are inefficiently spliced and polyadenylated. The major wave of genome activation in two-cell embryos involves expression of thousands of new genes. This unique pattern of gene expression is the product of maternal mRNAs recruited during maturation that encode for transcription factors and chromatin remodelers, as well as dramatic changes in chromatin structure due to incorporation of histone variants and modified histones. PMID- 26358878 TI - The Maternal-to-Zygotic Transition in Flowering Plants: Evidence, Mechanisms, and Plasticity. AB - The maternal-to-zygotic transition (MZT) defines a developmental phase during which the embryo progressively emancipates itself from a developmental control relying largely on maternal information. The MZT is a functional readout of two processes: the clearance of maternally derived information and the de novo expression of the inherited, parental alleles enabled by zygotic genome activation (ZGA). In plants, for many years the debate about whether the MZT exists at all focused on the ZGA alone. However, several recent studies provide evidence for a progressive alleviation of the maternal control over embryogenesis that is correlated with a gradual ZGA, a process that is itself maternally controlled. Yet, several examples of zygotic genes that are expressed and/or functionally required early in embryogenesis demonstrate a certain flexibility in the dynamics and kinetics of the MZT among plant species and also intraspecific hybrids. PMID- 26358879 TI - The Maternal-to-Zygotic Transition in Higher Plants: Available Approaches, Critical Limitations, and Technical Requirements. AB - Fertilization marks the turnover from the gametophyte to sporophyte generation in higher plants. After fertilization, sporophytic development undergoes genetic turnover from maternal to zygotic control: the maternal-to-zygotic transition (MZT). The MZT is thought to be critical for early embryogenesis; however, little is known about the time course or developmental impact of the MZT in higher plants. Here, we discuss what is known in the field and focus on techniques used in relevant studies and their limitations. Some significant questions and technical requirements for further investigations are also discussed. PMID- 26358876 TI - The Xenopus Maternal-to-Zygotic Transition from the Perspective of the Germline. AB - In Xenopus, the germline is specified by the inheritance of germ-plasm components synthesized at the beginning of oogenesis. Only the cells in the early embryo that receive germ plasm, the primordial germ cells (PGCs), are competent to give rise to the gametes. Thus, germ-plasm components continue the totipotent potential exhibited by the oocyte into the developing embryo at a time when most cells are preprogrammed for somatic differentiation as dictated by localized maternal determinants. When zygotic transcription begins at the mid-blastula transition, the maternally set program for somatic differentiation is realized. At this time, genetic control is ceded to the zygotic genome, and developmental potential gradually becomes more restricted within the primary germ layers. PGCs are a notable exception to this paradigm and remain transcriptionally silent until the late gastrula. How the germ-cell lineage retains full potential while somatic cells become fate restricted is a tale of translational repression, selective degradation of somatic maternal determinants, and delayed activation of zygotic transcription. PMID- 26358880 TI - The Maternal-to-Zygotic Transition. Preface. PMID- 26358881 TI - P2X7 receptor as predictor gene for glioma radiosensitivity and median survival. AB - Glioblastoma multiforme (GBM) is considered the most lethal intracranial tumor and the median survival time is approximately 14 months. Although some glioma cells present radioresistance, radiotherapy has been the mainstay of therapy for patients with malignant glioma. The activation of P2X7 receptor (P2X7R) is responsible for ATP-induced death in various cell types. In this study, we analyzed the importance of ATP-P2X7R pathway in the radiotherapy response P2X7R silenced cell lines, in vivo and human tumor samples. Both glioma cell lines used in this study present a functional P2X7R and the P2X7R silencing reduced P2X7R pore activity by ethidium bromide uptake. Gamma radiation (2Gy) treatment reduced cell number in a P2X7R-dependent way, since both P2X7R antagonist and P2X7R silencing blocked the cell cytotoxicity caused by irradiation after 24h. The activation of P2X7R is time-dependent, as EtBr uptake significantly increased after 24h of irradiation. The radiotherapy plus ATP incubation significantly increased annexin V incorporation, compared with radiotherapy alone, suggesting that ATP acts synergistically with radiotherapy. Of note, GL261 P2X7R silenced bearing mice failed in respond to radiotherapy (8Gy) and GL261 WT-bearing mice, that constitutively express P2X7R, presented a significant reduction in tumor volume after radiotherapy, showing in vivo that functional P2X7R expression is essential for an efficient radiotherapy response in gliomas. We also showed that a high P2X7R expression is a good prognostic factor for glioma radiosensitivity and survival probability in humans. Our data revealed the relevance of P2X7R expression in glioma cells to a successful radiotherapy response, and shed new light on this receptor as a useful predictor of the sensitivity of cancer patients to radiotherapy and median survival. PMID- 26358882 TI - Selective and Scalable Chemical Removal of Thin Single-Walled Carbon Nanotubes from their Mixtures with Double-Walled Carbon Nanotubes. AB - Double-walled carbon nanotubes (DWCNTs) are materials in high demand due to their superior properties. However, it is very challenging to prepare DWCNTs samples of high purity. In particular, the removal of single-walled carbon nanotubes (SWCNTs) contaminants is a major problem. Here, a procedure for a selective removal of thin-diameter SWCNTs from their mixtures with DWCNTs by lithium vapor treatment is investigated. The results are evaluated by Raman spectroscopy and in situ Raman spectroelectrochemistry. It is shown that the amount of SWCNTs was reduced by about 35 % after lithium vapor treatment of the studied SWCNTs-DWCNTs mixture. PMID- 26358883 TI - Different expression domains for two closely related amphibian TAARs generate a bimodal distribution similar to neuronal responses to amine odors. AB - Olfactory perception is mediated by a multitude of olfactory receptors, whose expression in the sensory surface, the olfactory epithelium, is spatially regulated. A common theme is the segregation of different olfactory receptors in different expression domains, which in turn leads to corresponding segregation in the neuronal responses to different odor groups. The amphibian olfactory receptor gene family of trace amine associated receptors, in short TAARs, is exceedingly small and allows a comprehensive analysis of spatial expression patterns, as well as a comparison with neuronal responses to the expected ligands for this receptor family, amines. Here we report that TAAR4b exhibits a spatial expression pattern characteristically different in two dimensions from that of TAAR4a, its close homolog. Together, these two genes result in a bimodal distribution resembling that of amine responses as visualized by calcium imaging. A stringent quantitative analysis suggests the involvement of additional olfactory receptors in amphibian responses to amine odors. PMID- 26358884 TI - Remodeling of motor units after nerve regeneration studied by quantitative electromyography. AB - OBJECTIVE: Peripheral nerve has the capacity to regenerate after nerve lesions; during reinnervation of muscle motor units are gradually reestablished. The aim of this study was to follow the time course of reestablishing and remodeling of motor units in relation to recovery of force after different types of nerve repair. METHODS: Reinnervation of muscle was compared clinically and electrophysiologically in complete median or ulnar nerve lesions with short gap lengths in the distal forearm repaired with a collagen nerve conduit (11 nerves) or nerve suture (10 nerves). Reestablishment of motor units was studied by quantitative EMG and recording of evoked compound muscle action potential (CMAP) during a 24-month observation period after nerve repair. RESULTS: Force recovered partially to about 80% of normal. Denervation activity gradually decreased during reinnervation though it was still increased at 24 months. Nascent motor unit potentials (MUPs) at early reinnervation were prolonged and polyphasic. During longitudinal studies, MUPs remained prolonged and their amplitudes gradually increased markedly. Firing of MUPs was unstable throughout the study. CMAPs gradually increased and the number of motor units recovered to approximately 20% of normal. There was weak evidence of CMAP amplitude recovery after suture ahead of conduit repair but without treatment related differences at 2 years. CONCLUSIONS: Surgical repair of nerve lesions with a nerve conduit or suture supported recovery of force and of motor unit reinnervation to the same extent. Changes occurred at a higher rate during early regeneration and slower after 12 months but should be followed for at least 2 years to assess outcome. EMG changes reflected extensive remodeling of motor units from early nascent units to a mature state with greatly enlarged units due to axonal regeneration and collateral sprouting and maturation of regenerated nerve and reinnervated muscle fibers after both types of repair. SIGNIFICANCE: Remodeling of motor units after peripheral nerve lesions provides the basis for better recovery of force than the number of motor axons and units. There were no differences after repair with a collagen nerve conduit and nerve suture at short nerve gap lengths. The reduced number of motor units indicates that further improvement of repair procedures and nerve environment is needed. PMID- 26358885 TI - Validation of the Behavioural Indicators of Pain Scale ESCID for pain assessment in non-communicative and mechanically ventilated critically ill patients: a research protocol. AB - AIM: To investigate the validity and reliability of the Behavioural Indicators of Pain Scale (ESCID) in medically and surgically non-communicative and mechanically ventilated critical patients. BACKGROUND: Scales based on behavioural indicators of pain are suggested to measure pain in non-communicative critically ill patients. Scales proposed thus far have a range not comparable to those used with patients who can report their pain. A scale with a 0-10 range and more behavioural indicators is proposed to improve the detection and measurement of pain. DESIGN: A multicentre prospective observational design to validate a scale measuring instrument. METHODS: Three hundred non-communicative and mechanically ventilated critical patients from 20 different intensive care units will be observed for 5 minutes before, during and 15 minutes after three procedures: turning, tracheal suctioning and soft friction with gauze on healthy tissue. Two independent observers will assess the pain of subjects with the Behavioural Pain Scale and the ESCID scale simultaneously. Descriptive and inferential statistics will be used. Student's t-test will be used to compare components of the twos scales. Inter-rater and intrarater agreement will be investigated. The reliability scale will be measured using Cronbach's alpha. Approval date for this protocol was January 2012. DISCUSSION: A greater number of behavioural indicators in the ESCID scale than in previously validated scales, with a 0-10 score range, can improve the detection and measurement of pain in non-communicative and mechanically ventilated critical patients. Funding granted in 2011 by the Spanish Health Research Fund (PI 11/00766, Health Ministry). TRIAL REGISTRATION: Study registered with www.clinicaltrials.gov (NCT01744717). PMID- 26358887 TI - A Fluorescent Molecular Probe for the Detection of Hydrogen Based on Oxidative Addition Reactions with Crabtree-Type Hydrogenation Catalysts. AB - A Crabtree-type Ir(I) complex tagged with a fluorescent dye (bodipy) was synthesized. The oxidative addition of H2 converts the weakly fluorescent Ir(I) complex (Phi=0.038) into a highly fluorescent Ir(III) species (Phi=0.51). This fluorogenic reaction can be utilized for the detection of H2 and to probe the oxidative addition step in the catalytic hydrogenation of olefins. PMID- 26358888 TI - Migrated Avalon Veno-Venous Extracorporeal Membrane Oxygenation Cannula: How to Adjust Without Interruption of Flow. AB - The Avalon dual lumen cannula is presently the cannula of choice for veno-venous extracorporeal membrane oxygenation (VV-ECMO) via right internal jugular cannulation. This cannula establishes VV-ECMO with a single cannulation; however, it requires appropriate positioning to gain adequate oxygenation. Malposition of this cannula can cause inadequate ECMO flow, hypoxia, and structural injury. We have experienced two cases of migration: one into the hepatic vein and the other into the right ventricle. The former was repositioned using echocardiographic guidance without using a guidewire. The latter was repositioned using a guidewire from the femoral vein under fluoroscopy, without antegrade wire placement into the Avalon cannula, discontinuation of ECMO, or bleeding. PMID- 26358886 TI - Insulin Attenuates Beta-Amyloid-Associated Insulin/Akt/EAAT Signaling Perturbations in Human Astrocytes. AB - The excitatory amino acid transporters 1 and 2 (EAAT1 and EAAT2), mostly located on astrocytes, are the main mediators for glutamate clearance in humans. Malfunctions of these transporters may lead to excessive glutamate accumulation and subsequent excitotoxicity to neurons, which has been implicated in many kinds of neurodegenerative disorders including Alzheimer's disease (AD). Yet, the specific mechanism of the glutamate system dysregulation remains vague. To explore whether the insulin/protein kinase B (Akt)/EAAT signaling in human astrocytes could be disturbed by beta-amyloid protein (Abeta) and be protected by insulin, we incubated HA-1800 cells with varying concentrations of Abeta1-42 oligomers and insulin. Then the alterations of several key substrates in this signal transduction pathway were determined. Our results showed that expressions of insulin receptor, phospho-insulin receptor, phospho-protein kinase B, phospho mammalian target of rapamycin, and EAAT1 and EAAT2 were decreased by the Abeta1 42 oligomers in a dose-dependent manner (p < 0.05) and this trend could be recovered by insulin treatment (p < 0.05). However, the expressions of total Akt and mTOR were invariant (p > 0.05), and the mRNA levels of EAAT1 and EAAT2 were also unchanged (p > 0.05). Taken together, this study indicates that Abeta1-42 oligomers could cause disturbances in insulin/Akt/EAAT signaling in astrocytes, which might be responsible for AD onset and progression. Additionally, insulin can exert protective functions to the brain by modulating protein modifications or expressions. PMID- 26358889 TI - Utility of autoantibodies as biomarkers for diagnosis and staging of neurodegenerative diseases. AB - Autoantibodies are self-reactive antibodies that have been widely implicated as causal agents of autoimmune diseases. They are found in the blood of all human sera, regardless of age, gender, or the presence or absence of disease. While the underlying reason for their ubiquity remains unknown, it has been hypothesized that they participate in the clearance of blood-borne cell and tissue debris generated in both healthy and diseased individuals on a daily basis. Although much evidence supports this debris clearance role, recent studies also suggest a causal role for autoantibodies in disease. This chapter first presents well-known examples of autoimmune diseases that emphasize a direct causal role for autoantibodies and then discusses the veritable explosion of evidence now supporting their involvement in a wide variety of other diseases, including cancers and several types of neurological and neurodegenerative diseases. Lastly, translational strategies that take advantage of the "cause and/or effect" role of autoantibodies and recent technological advancements in their detection to exploit autoantibodies as sensitive and specific biomarkers useful for the detection and diagnosis of disease are outlined. Their use in the diagnosis and staging of Alzheimer's and Parkinson's diseases is presented, and future applications in clinical medicine and basic science are highlighted. PMID- 26358890 TI - Metabolomics of neurodegenerative diseases. AB - Neurodegenerative diseases are progressive, devastating, and terminal, carrying both personal and societal burden. Currently, their diagnosis depends on their clinical presentation. No quantitative biomarkers exist to enable early verdict and commencement of therapy. The lack of diagnostic biomarkers stems from the unavailability of brain tissue, the complexity and heterogeneity of the brain and neurodegenerative pathology, and the fact that peripheral tissues such as blood, urine, and even cerebrospinal fluid might not reflect early stages of brain pathology. Moreover, accumulated evidence indicates the majority of these diseases are not genetically inherited; rather, the genes bring about the risk to develop them, but the trigger is not known. As metabolites are at the intersection between the genetic background of a cell or a tissue and the environmental effects on the same, metabolomics has emerged as a field with great promise to deliver new, biologically, and clinically relevant biomarkers for neurodegenerative disorders. Here, we review the basic principles of metabolomics and focus on studies performed in most common neurodegenerative diseases, such as Alzheimer's, Parkinson's, and Huntington's diseases, Multiple sclerosis, and Amyotrophic lateral sclerosis. PMID- 26358891 TI - Parkinson's disease: in vivo brain metabolomics by MRS. AB - In vivo brain metabolomics in Parkinson's disease is still in its infancy. This chapter will review brain metabolomics in the human brain as studied noninvasively by magnetic resonance spectroscopy. Although preliminary, the results shed some light on the pathophysiology of Parkinson's disease. PMID- 26358892 TI - Recent advances and applications of metabolomics to investigate neurodegenerative diseases. AB - Metabolomics is gaining an important role in the investigation of neurological pathologies such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis which are characterized by the absence of reliable diagnostic markers. The magnitude of emotional, physical, and financial burden related to these three devastating pathologies can be deduced considering that nearly 20 million people worldwide suffer from these three pathologies. In this chapter, an overview of the recent advances and applications of metabolomics to investigate these major neurodegenerative diseases will be presented. Metabolomics strategies are now being developed to map potential perturbations in biochemical pathways linked to neurodegeneration. Going further, there is more and more evidence supporting the concept that these pathologies can begin years or even decades before the onset of clinical symptoms, and thus, metabolomics is also increasingly being used to discover preclinical biomarkers of these neurological diseases. PMID- 26358893 TI - Lipidomics of human brain aging and Alzheimer's disease pathology. AB - Lipids stimulated and favored the evolution of the brain. Adult human brain contains a large amount of lipids, and the largest diversity of lipid classes and lipid molecular species. Lipidomics is defined as "the full characterization of lipid molecular species and of their biological roles with respect to expression of proteins involved in lipid metabolism and function, including gene regulation." Therefore, the study of brain lipidomics can help to unravel the diversity and to disclose the specificity of these lipid traits and its alterations in neural (neurons and glial) cells, groups of neural cells, brain, and fluids such as cerebrospinal fluid and plasma, thus helping to uncover potential biomarkers of human brain aging and Alzheimer disease. This review will discuss the lipid composition of the adult human brain. We first consider a brief approach to lipid definition, classification, and tools for analysis from the new point of view that has emerged with lipidomics, and then turn to the lipid profiles in human brain and how lipids affect brain function. Finally, we focus on the current status of lipidomics findings in human brain aging and Alzheimer's disease pathology. Neurolipidomics will increase knowledge about physiological and pathological functions of brain cells and will place the concept of selective neuronal vulnerability in a lipid context. PMID- 26358895 TI - One-Pot Synthesis of Carbon-Coated Nanostructured Iron Oxide on Few-Layer Graphene for Lithium-Ion Batteries. AB - Nanostructure engineering has been demonstrated to improve the electrochemical performance of iron oxide based electrodes in Li-ion batteries (LIBs). However, the synthesis of advanced functional materials often requires multiple steps. Herein, we present a facile one-pot synthesis of carbon-coated nanostructured iron oxide on few-layer graphene through high-pressure pyrolysis of ferrocene in the presence of pristine graphene. The ferrocene precursor supplies both iron and carbon to form the carbon-coated iron oxide, while the graphene acts as a high surface-area anchor to achieve small metal oxide nanoparticles. When evaluated as a negative-electrode material for LIBs, our composite showed improved electrochemical performance compared to commercial iron oxide nanopowders, especially at fast charge/discharge rates. PMID- 26358896 TI - Insomnia in workers with delayed recovery from mild traumatic brain injury. AB - OBJECTIVE/BACKGROUND/AIM: Insomnia has not been explored as it relates to recovery after mild traumatic brain injury (mTBI). We aimed to evaluate the prevalence of insomnia among Ontario workers with delayed recovery from mTBI, and its relationship with sociodemographic, TBI- and claim-related, behavioral, and clinical factors. PATIENTS/METHODS: This was a cross-sectional study carried out over a period of 24 months in a large rehabilitation hospital in Ontario. To assess the prevalence of insomnia, we used the Insomnia Severity Index (ISI). Data were collected from standardized questionnaires, insurer records, and clinical assessment at the time of recruitment. Bivariate associations were calculated using the Spearman's correlation coefficient or analysis of variance. We established stepwise multivariate linear regression models of factors associated with insomnia. Additional analyses, including the assessment of the internal consistency of the ISI, were performed. RESULTS: Of the 94 participants diagnosed with mTBI, clinical insomnia was reported by 69.2%. The mean age was 45.20 +/- 9.94 years; 61.2% were men. No sex-related differences were observed in insomnia prevalence or severity. Insomnia was significantly associated with certain sociodemographic, claim-related, behavioral, and clinical variables. In the multivariable regression analysis, several determinants explained 53% of the insomnia variance. The internal consistency of the ISI, as measured by Cronbach's alpha, was 0.86. CONCLUSIONS: Insomnia is common in persons with delayed recovery from mTBI, and is significantly associated with potentially modifiable clinical and nonclinical variables. Care of persons with brain injury requires greater attention with regard to the diagnosis and management of insomnia and associated disorders. PMID- 26358897 TI - Development of an indirect ELISA assay for the detection of IgG antibodies against the ORF1 of Torque teno sus viruses 1 and 2 in conventional pigs. AB - Torque teno sus viruses (TTSuV, family Anelloviridae) cause long lasting and persistent infection in pigs under subclinical scenarios, and are potentially linked to several economically important swine diseases. Currently, little is known about swine immune response against TTSuV infections. In this study, an ELISA assay was developed based on the ORF1-A recombinant protein of two known TTSuVs, namely TTSuV1 (genus Iotatorquevirus) and TTSuV2 (genus Kappatorquevirus). The assay was used to study the development of the humoral immune response against TTSuV1 and TTSuV2 in longitudinally sampled clinically healthy pigs and their dams. Anti ORF1-A IgG was found in serum of pigs and sows for both TTSuVs. From 15 sows, 15 (100%) and 13 (83%) had anti ORF1-A IgG against TTSuV1 and TTSuV2, respectively. Pig sero-prevalences at the first sampling (4 weeks of age) were 65% (24/37) and 5% (2/37) for TTSuV1 and TTSuV2, respectively. For TTSuV1, the highest anti ORF1-A IgG prevalence was observed at weeks 21 and 25, with 68% (25/37) sero-positive pigs. Quantitative PCR (qPCR) results at week 21 revealed that 26 out of 32 (81%) pigs were positive for TTSuV1. In the case of TTSuV2, the highest anti ORF1-A IgG prevalence was observed at week 21, with 84% (31/37) pigs being sero-positive. At the same week, 92% (34/37) of pigs were qPCR positive. In summary, anti ORF1-A IgGs were detected in both sows and piglets at different ages, indicating that these animals could mount a humoral immune response against both TTSuVs. However, the high percentage of viremic pigs in presence of anti ORF1-A IgG suggests that these antibodies are not able to remove TTSuVs from circulation. PMID- 26358898 TI - Immune response of porcine alveolar macrophages to a concurrent infection with porcine reproductive and respiratory syndrome virus and Haemophilus parasuis in vitro. AB - Porcine reproductive and respiratory syndrome virus (PRRSV) can predispose pigs to secondary respiratory infection with bacteria such as Haemophilus parasuis. Animals infected with both pathogens develop more severe clinical disease. The immune response of porcine alveolar macrophages (PAMs) to simultaneous infection with PRRSV and H. parasuis was analysed in vitro, describing cytokine production, expression of cell surface molecules, and production of reactive oxygen species (ROS). Concurrent infection with PRRSV and H. parasuis increased gene expression of pro-inflammatory cytokines (TNF-alpha, IL-1beta, IL-8) in PAMs in comparison with PAMs infected with PRRSV or H. parasuis alone. An additive effect of dual infection on IL-1beta production was confirmed at the protein level. PAMs infected with PRRSV showed increased production of ROS compared to controls. Conversely, simultaneous infection of PAMs with PRRSV and H. parasuis decreased production of ROS, indicating the presence of an H. parasuis defence mechanism against respiratory burst. Concurrent infection of PAMs with PRRSV and H. parasuis was shown to elicit a pro-inflammatory immune response represented by significant IL-1beta production. Severe multifactorial respiratory disease in natural conditions caused by both pathogens could be the consequence of pro inflammatory mediated immunopathology. PMID- 26358899 TI - Thyroid hormones--From Crystal Packing to Activity to Reactivity. PMID- 26358900 TI - Hybrid Repair for Anastomotic Pseudoaneurysm on the Innominate Artery Following Blunt Chest Trauma. AB - A 55-year-old male with a previous open surgical repair of a traumatic right subclavian artery rupture was admitted following a fall with a rupture of the bifurcation of the innominate artery. The right common carotid artery was debranched from the left common carotid artery using a ringed 8 mm vascular graft. Simultaneously, a 16 * 80 mm vascular stent graft was inserted from the origin of the innominate artery to the mid portion of the subclavian artery, successfully covering the rupture site. PMID- 26358901 TI - Studies of Metabolism Using (13)C MRS of Hyperpolarized Probes. AB - First described in 2003, the dissolution dynamic nuclear polarization (DNP) technique, combined with (13)C magnetic resonance spectroscopy (MRS), has since been used in numerous metabolic studies and has become a valuable metabolic imaging method. DNP dramatically increases the level of polarization of (13)C labeled compounds resulting in an increase in the signal-to-noise ratio (SNR) of over 50,000 fold for the MRS spectrum of hyperpolarized compounds. The high SNR enables rapid real-time detection of metabolism in cells, tissues, and in vivo. This chapter will present a comprehensive review of the DNP approaches that have been used to monitor metabolism in living systems. First, the list of (13)C DNP probes developed to date will be presented, with a particular focus on the most commonly used probe, namely [1-(13)C] pyruvate. In the next four sections, we will then describe the different factors that need to be considered when designing (13)C DNP probes for metabolic studies, conducting in vitro or in vivo hyperpolarized experiments, as well as acquiring, analyzing, and modeling hyperpolarized (13)C data. PMID- 26358903 TI - Metabolic Tracing Using Stable Isotope-Labeled Substrates and Mass Spectrometry in the Perfused Mouse Heart. AB - There has been a resurgence of interest for the field of cardiac metabolism catalyzed by evidence demonstrating a role of metabolic dysregulation in the pathogenesis of heart disease as well as the increased need for new therapeutic targets for patients with these diseases. In this regard, measuring substrate fluxes is critical in providing insight into the dynamics of cellular metabolism and in delineating the regulation of metabolite production and utilization. This chapter provides a comprehensive description of concepts, guidelines, and tips to assess metabolic fluxes relevant to energy substrate metabolism using (13)C labeled substrates and (13)C-isotopomer analysis by gas chromatography-mass spectrometry (GC-MS), and the ex vivo working heart as study model. The focus will be on the mouse and on flux parameters, which are commonly assessed in the field, namely, those relevant to substrate selection for energy metabolism, specifically the relative contribution of carbohydrate (glucose, lactate, and pyruvate) and fatty acid oxidation to acetyl-CoA formation for citrate synthesis, glycolysis, as well as anaplerosis. We provide detailed procedures for the heart isolation and perfusion in the working mode as well as for sample processing for metabolite extraction and analysis by GC-MS and subsequent data processing for calculation of metabolic flux parameters. Finally, we address practical considerations and discuss additional applications and future challenges. PMID- 26358902 TI - Hyperpolarized (13)C Magnetic Resonance and Its Use in Metabolic Assessment of Cultured Cells and Perfused Organs. AB - Diseased tissue is often characterized by abnormalities in intermediary metabolism. Observing these alterations in situ may lead to an improved understanding of pathological processes and novel ways to monitor these processes noninvasively in human patients. Although (13)C is a stable isotope safe for use in animal models of disease as well as human subjects, its utility as a metabolic tracer has largely been limited to ex vivo analyses employing analytical techniques like mass spectrometry or nuclear magnetic resonance spectroscopy. Neither of these techniques is suitable for noninvasive metabolic monitoring, and the low abundance and poor gyromagnetic ratio of conventional (13)C make it a poor nucleus for imaging. However, the recent advent of hyperpolarization methods, particularly dynamic nuclear polarization (DNP), makes it possible to enhance the spin polarization state of (13)C by many orders of magnitude, resulting in a temporary amplification of the signal sufficient for monitoring kinetics of enzyme-catalyzed reactions in living tissue through magnetic resonance spectroscopy or magnetic resonance imaging. Here, we review DNP techniques to monitor metabolism in cultured cells, perfused hearts, and perfused livers, focusing on our experiences with hyperpolarized [1-(13)C]pyruvate. We present detailed approaches to optimize the DNP procedure, streamline biological sample preparation, and maximize detection of specific metabolic activities. We also discuss practical aspects in the choice of metabolic substrates for hyperpolarization studies and outline some of the current technical and conceptual challenges in the field, including efforts to use hyperpolarization to quantify metabolic rates in vivo. PMID- 26358905 TI - Analysis of Cell Metabolism Using LC-MS and Isotope Tracers. AB - Here we discuss our methods to analyze small polar compounds involved in central carbon metabolism using LC-MS. Methods described include sample extraction procedures for cells and medium, as well as for plasma/serum, urine, CSF, and tissue samples. Different extraction solvents are assessed. Our methods for using (13)C stable isotope tracers to examine the kinetics and distributions of mass isotopologues of many metabolites are discussed. Quantification methods are described for (13)C stable isotope tracer experiments as well as for unlabeled experiments. These methods were applied in a fumarate hydratase deficient cell model to show how isotope tracing can demonstrate shifts in metabolic pathways and, together with metabolite exchange rates, can be used to gain insights into changes in cell metabolism. PMID- 26358904 TI - Probing Metabolism in the Intact Retina Using Stable Isotope Tracers. AB - Vertebrate retinas have several characteristics that make them particularly interesting from a metabolic perspective. The retinas have a highly laminated structure, high energy demands, and they share several metabolic features with tumors, such as a strong Warburg effect and abundant pyruvate kinase M2 isoform expression. The energy demands of retinas are both qualitatively and quantitatively different in light and darkness and metabolic dysfunction could cause retinal degeneration. Stable isotope-based metabolic analysis with mass spectrometry is a powerful tool to trace the dynamic metabolic reactions and reveal novel metabolic pathways within cells and between cells in retina. Here, we describe methods to quantify retinal metabolism in intact retinas and discuss applications of these methods to the understanding of neuron-glia interaction, light and dark adaptation, and retinal degenerative diseases. PMID- 26358906 TI - Analysis of Fatty Acid Metabolism Using Stable Isotope Tracers and Mass Spectrometry. AB - Cells can synthesize fatty acids by ligating multiple acetyl units from acetyl CoA. This is followed by desaturation and elongation reactions to produce a variety of fatty acids required for proper cellular functioning. Alternatively, exogenous lipid sources can contribute to cellular fatty acid pools. Here, we present a method based on incorporation of (13)C-carbon from labeled substrates into fatty acids and subsequent mass spectrometry analysis. The resulting labeling patterns can be used to determine (1) (13)C-enrichment of lipogenic acetyl-CoA, (2) the relative contributions of synthesis and uptake, and (3) absolute fatty acid fluxes. We begin by providing a background and general principles regarding the use of stable isotopes to study fatty acid metabolism. We then proceed with detailing procedures for sample preparation and both GC-MS and LC-MS analysis of isotope incorporation. Finally, we discuss the interpretation of the resulting fatty acid-labeling patterns. PMID- 26358907 TI - Dynamic Proteomics: In Vivo Proteome-Wide Measurement of Protein Kinetics Using Metabolic Labeling. AB - Control of biosynthetic and catabolic rates of polymers, including proteins, stands at the center of phenotype, physiologic adaptation, and disease pathogenesis. Advances in stable isotope-labeling concepts and mass spectrometric instrumentation now allow accurate in vivo measurement of protein synthesis and turnover rates, both for targeted proteins and for unbiased screening across the proteome. We describe here the underlying principles and operational protocols for measuring protein dynamics, focusing on metabolic labeling with (2)H2O (heavy water) combined with tandem mass spectrometric analysis of mass isotopomer abundances in trypsin-generated peptides. The core principles of combinatorial analysis (mass isotopomer distribution analysis or MIDA) are reviewed in detail, including practical advantages, limitations, and technical procedures to ensure optimal kinetic results. Technical factors include heavy water labeling protocols, optimal duration of labeling, clean up and simplification of sample matrices, accurate quantitation of mass isotopomer abundances in peptides, criteria for adequacy of mass spectrometric abundance measurements, and calculation algorithms. Some applications are described, including the noninvasive "virtual biopsy" strategy for measuring molecular flux rates in tissues through measurements in body fluids. In addition, application of heavy water labeling to measure flux lipidomics is noted. In summary, the combination of stable isotope labeling, particularly from (2)H2O, with tandem mass spectrometric analysis of mass isotopomer abundances in peptides, provides a powerful approach for characterizing the dynamics of proteins across the global proteome. Many applications in research and clinical medicine have been achieved and many others can be envisioned. PMID- 26358908 TI - Non-targeted Tracer Fate Detection. AB - Stable isotopes have been used to trace atoms through metabolism and quantify metabolic fluxes for several decades. Only recently non-targeted stable isotope labeling approaches have emerged as a powerful tool to gain insights into metabolism. However, the manual detection of isotopic enrichment for a non targeted analysis is tedious and time consuming. To overcome this limitation, the non-targeted tracer fate detection (NTFD) algorithm for the automated metabolome wide detection of isotopic enrichment has been developed. NTFD detects and quantifies isotopic enrichment in the form of mass isotopomer distributions (MIDs) in an automated manner, providing the means to trace functional groups, determine MIDs for metabolic flux analysis, or detect tracer-derived molecules in general. Here, we describe the algorithmic background of NTFD, discuss practical considerations for the freely available NTFD software package, and present potential applications of non-targeted stable isotope labeling analysis. PMID- 26358909 TI - Isotopomer Spectral Analysis: Utilizing Nonlinear Models in Isotopic Flux Studies. AB - We present the principles underlying the isotopomer spectral analysis (ISA) method for evaluating biosynthesis using stable isotopes. ISA addresses a classic conundrum encountered in the use of radioisotopes to estimate biosynthesis rates whereby the information available is insufficient to estimate biosynthesis. ISA overcomes this difficulty capitalizing on the additional information available from the mass isotopomer labeling profile of a polymer. ISA utilizes nonlinear regression to estimate the two unknown parameters of the model. A key parameter estimated by ISA represents the fractional contribution of the tracer to the precursor pool for the biosynthesis, D. By estimating D in cells synthesizing lipids, ISA quantifies the relative importance of two distinct pathways for flux of glutamine to lipid, reductive carboxylation, and glutaminolysis. ISA can also evaluate the competition between different metabolites, such as glucose and acetoacetate, as precursors for lipogenesis and thereby reveal regulatory properties of the biosynthesis pathway. The model is flexible and may be expanded to quantify sterol biosynthesis allowing tracer to enter the pathway at three different positions, acetyl CoA, acetoacetyl CoA, and mevalonate. The nonlinear properties of ISA provide a method of testing for the presence of gradients of precursor enrichment illustrated by in vivo sterol synthesis. A second ISA parameter provides the fraction of the polymer that is newly synthesized over the time course of the experiment. In summary, ISA is a flexible framework for developing models of polymerization biosynthesis providing insight into pools and pathway that are not easily quantified by other techniques. PMID- 26358910 TI - Effect of Error Propagation in Stable Isotope Tracer Studies: An Approach for Estimating Impact on Apparent Biochemical Flux. AB - Stable isotope tracers are widely used to quantify metabolic rates, and yet a limited number of studies have considered the impact of analytical error on estimates of flux. For example, when estimating the contribution of de novo lipogenesis, one typically measures a minimum of four isotope ratios, i.e., the precursor and product labeling pre- and posttracer administration. This seemingly simple problem has 1 correct solution and 80 erroneous outcomes. In this report, we outline a methodology for evaluating the effect of error propagation on apparent physiological endpoints. We demonstrate examples of how to evaluate the influence of analytical error in case studies concerning lipid and protein synthesis; we have focused on (2)H2O as a tracer and contrast different mass spectrometry platforms including GC-quadrupole-MS, GC-pyrolysis-IRMS, LC quadrupole-MS, and high-resolution FT-ICR-MS. The method outlined herein can be used to determine how to minimize variations in the apparent biology by altering the dose and/or the type of tracer. Likewise, one can facilitate biological studies by estimating the reduction in the noise of an outcome that is expected for a given increase in the number of replicate injections. PMID- 26358911 TI - Metabolic Analysis Using Stable Isotopes. Preface. PMID- 26358912 TI - Systematic Investigation of High-Sensitivity Luminescent Sensing for Polyoxometalates and Iron(III) by MOFs Assembled with a New Resorcin[4]arene Functionalized Tetracarboxylate. AB - A new family of resorcin[4]arene-based metal-organic frameworks (MOFs), namely, [Eu(HL)(DMF)(H2 O)2 ]?3 H2 O (1), [Tb(HL)(DMF)(H2 O)2 ] 3 H2 O (2), [Cd4 (L)2 (DMF)4 (H2 O)2 ] 3 H2 O (3) and [Zn3 (HL)2 (H2 O)2 ] 2 DMF?7 H2 O (4), have been constructed from a new resorcin[4]arene-functionalized tetracarboxylic acid (H4 L=2,8,14,20-tetra-ethyl-6,12,18,24-tetra-methoxy-4,10,16,22-tetra-carboxy-methoxy calix[4]arene). Isostructural 1 and 2 exhibit charming 1D motifs built with the cup-like HL(3-) anions and rare earth cations. Compounds 3 and 4 show a unique sandwich-based 2D layer and a fascinating 3D framework, respectively. Remarkably, compounds 1 and 2 display intensive red and green emissions triggered by the efficient antenna effect of organic ligands under UV light. More importantly, systematic luminescence studies demonstrate that Ln-MOFs 1 and 2, as efficient multifunctional fluorescent materials, show highly selective and sensitive sensing of Fe(3+) , polyoxometalates (POMs), and acetone, which represents a rare example of a sensor for quantitatively detecting three different types of analytes. This is also an exceedingly rare example of Fe(3+) and POMs detection in aqueous solutions employing resorcin[4]arene-based luminescent Ln-MOFs. Furthermore, the possible mechanism of the sensing properties is deduced. PMID- 26358914 TI - Laboratory-based investigation of suspected mumps cases submitted to the German National Reference Centre for Measles, Mumps, and Rubella, 2008 to 2013. AB - From 2008 to 2013, sample sets from 534 patients displaying clinical symptoms of mumps were submitted to the German Reference Centre for Measles, Mumps and Rubella. Mumps virus infection was confirmed in 216 cases (40%) by PCR and/or serology. Confirmed cases were more frequently seen in male than in female patients (128 vs. 81); the age group predominantly affected was 15 to 29 years old (65%, median age: 26.4 years). The majority of the confirmed cases had a remote history of vaccination with one or two doses of a mumps-containing vaccine (69%). Our results indicate that mumps virus caused two outbreaks in Bavaria in 2008 and 2010/2011 and a third one in Lower Saxony in 2011. Mumps virus genotype G was preponderantly detected from 2008 to 2013. For 107 of the 216 patients with a confirmed mumps infection, we correlated the results from PCR and serology. PCR detected cases during the first week after onset of symptoms (74% positive results). PCR worked best with throat swabs and oral fluids (61% and 60% positive results, respectively). IgM was more reliable with a longer time after onset of symptoms (67%), but indirect IgM serology was of insufficient sensitivity for vaccinated mumps cases (30%); the IgM MU-capture assay detected more cases in this group. Mumps virus is able to initiate an infection in vaccinated patients (secondary vaccine failure, SVF) although it is unclear to what extent. Since SVF does occur in highly vaccinated populations and IgM will not increase to detectable levels in all SVF patients, we strongly recommend using PCR plus serology tests to avoid false-negative diagnoses in vaccinated individuals with clinical signs of mumps. PMID- 26358913 TI - The prevalence of human papillomavirus in squamous cell carcinoma of unknown primary site metastatic to neck lymph nodes: a systematic review. AB - A subset of head and neck squamous cell carcinoma, which mainly arise from the crypt epithelium of the palatine and lingual tonsils, may be caused by high-risk human papillomavirus (HPV) infections. This topographical restriction together with other overlapping clinical features have led investigators to suspect that HPV plays a role in squamous cell carcinoma of unknown primary (SCCUP) site metastatic to neck lymph nodes. We performed a systematic review of articles listed in PubMed to identify studies testing HPV and/or p16(INK4a) status (p16) in tissue samples from initial and definitive SCCUP. The prevalence of HPV related (HPV DNA-positive and/or p16 positive) SCCUP was calculated for all the SCCUP, initial SCCUP, suspected definitive SCCUP, and true definitive SCCUP whenever a minimum of 10 cases of each category was identified. In addition, data concerning patients' diagnostic work-up, the HPV detection methods, and the correlations between HPV-status, the localization of the occult primary tumor, and the clinical outcome were also extracted. Eighteen retrospective cohort studies, assessing a total of 659 patients, met the inclusion criteria. The overall median prevalences of HPV-DNA(pos), of p16(pos), and of positivity for both HPV markers were, respectively, 37.0, 48.5, and 36.0 %. Patients with diagnosis of initial SCCUP had overall median prevalences of HPV-DNA(pos), of p16(pos), and of positivity for both HPV markers, respectively, of 81.8, 86.2, and 80.8 %. The data uncovered by this systematic review confirm that SCCUP is frequently causally associated to HPV-driven oropharyngeal squamous cell carcinomas. This finding supports the view that HPV-status could be routinely assessed in SCCUP patients as it may lead to identifying the primary tumor and the decision to de-escalate treatment. PMID- 26358915 TI - Estimation of the sensitivity and specificity of a Leptospira spp. in-house ELISA through Bayesian modelling. AB - The microscopic agglutination test (MAT) is still considered the gold standard for the diagnosis of leptospirosis, although studies have shown that the test is an imperfect gold standard for clinical samples and unsuitable for epidemiological studies. Here, test characteristics of an in-house ELISA were identified for both subclinical and clinical populations by Bayesian latent class models. A conditional dependence model for two diagnostic tests and two populations was adapted to analyse a clinical and a subclinical scenario, respectively. These Bayesian models were used to estimate the sensitivity and specificity of the in-house ELISA and the MAT as well as the prevalences. The Bayesian estimates of the in-house ELISA were: clinical sensitivity=83.0%, clinical specificity=98.5%, subclinical sensitivity=85.7% and subclinical specificity=99.1%. In contrast, the estimates of the MAT were: clinical sensitivity=65.6%, clinical specificity=97.7%, subclinical sensitivity 54.9% and subclinical specificity=97.3%. The results show the suitability of the in-house ELISA for both clinical investigations and epidemiological studies in mildly endemic areas. PMID- 26358916 TI - Epidemiology of healthcare associated infections in Germany: Nearly 20 years of surveillance. AB - OBJECTIVE: To describe the epidemiology of healthcare-associated infections (HAI) in hospitals participating in the German national nosocomial infections surveillance system (KISS). METHOD: The epidemiology of HAI was described for the surveillance components for intensive care units (ITS-KISS), non-ICUs (STATIONS KISS), very low birth weight infants (NEO-KISS) and surgical site infections (OP KISS) in the period from 2006 to 2013. In addition, risk factor analyses were performed for the most important infections of ICU-KISS, NEO-KISS and OP-KISS. RESULTS: Data from a total of 3,454,778 ICU patients from 913 ICUs, 618,816 non ICU patients from 142 non-ICU wards, 53,676 VLBW from 241 neonatal intensive care units (NICU) and 1,005,064 surgical patients from operative departments from 550 hospitals were used for analysis. Compared with baseline data, a significant reduction of primary bloodstream infections (PBSI) and lower respiratory tract infections (LRTI) was observed in ICUs with the maximum effect in year 5 (or longer participation) (incidence rate ratio 0.60 (CI95 0.50-0.72) and 0.61 (CI95 0.52-0.71) respectively). A significant reduction of PBSI and LRTI was also observed in NEO-KISS when comparing the baseline situation with the 5th year of participation (hazard ratio 0.70 (CI95 0.64-0.76) and 0.43 (CI95 0.35-0.52)). The effect was smaller in operative departments after the introduction of OP-KISS (OR 0.80; CI95 0.64-1.02 in year 5 or later for all procedure types combined). Due to the large database, it has not only been possible to confirm well-known risk factors for HAI, but also to identify some new interesting risk factors like seasonal and volume effects. CONCLUSIONS: Participating in a national surveillance system and using surveillance data for internal quality management leads to substantial reduction of HAI. In addition, a surveillance system can identify otherwise not recognized risk factors which should - if possible - be considered for infection control management and for risk adjustment in the benchmarking process. PMID- 26358917 TI - Identification and characterization of episomal forms of integrative genomic islands in the genus Francisella. AB - Recently, we identified a putative prophage on a genomic island (GI) within the genome sequence of Francisella hispaniensis isolate AS0-814 (Francisella tularensis subsp. novicida-like 3523) by the analysis of the CRISPR-Cas systems of Francisella. Various spacer DNAs within the CRISPR region of different F. tularensis subsp. novicida strains were found to be homologous to the putative prophage (Schunder et al., 2013, Int. J. Med. Microbiol. 303:51-60). Now we identified the GI (FhaGI-1) as a mobile element which is able to form a circular episomal structure. The circular episomal form of FhaGI-1 is generated by F. hispaniensis, and the excision of the island is an integrase-dependent and site specific process. Furthermore, we could demonstrate that the excision of the island is also possible in other bacterial species (Escherichia coli). In addition, we could show that a genetically generated small variant of the island is also functional and, after its electroporation into strain F. tularensis subsp. holarctica LVS, the GI was stable and site-specifically integrated into the genome of the transformants. The integrase is sufficient for the integration and excision of the small variant into and from the DNA backbone, respectively. Thus, the element may be suitable to be used as a genetic tool in F. tularensis research. Furthermore, we identified the tRNA(Val) gene of Francisella as an integration site for GIs. Genomic island FphGI-1 was identified in Francisella philomiragia ATCC 25016. We were not able to detect the episomal form of this GI, probably due to a mutated attR site. However, we could demonstrate that integrative GIs are present in Francisella and that they may allow horizontal gene transfer between different Francisella species. PMID- 26358918 TI - The ability of feline spermatozoa in different epididymal regions to undergo capacitation and acrosome reaction. AB - The sperm maturation process that occurs in the epididymis is a necessary process for spermatozoa to acquire motility and the ability to undergo capacitation, which is an important key for fertilization. The aim of this study was to evaluate the ability of feline spermatozoa from different regions of the epididymis to undergo capacitation and acrosome reaction. Experiment I: epididymal spermatozoa from caput, corpus and cauda regions were placed in phosphate buffered saline (control medium) and in vitro fertilization medium (capacitating conditions). Sperm motility, motility patterns, plasma membrane integrity and tyrosine phosphorylation were evaluated at time 0 and 60min after incubation. Experiment II: spermatozoa were treated with 2MUM of calcium ionophore (A23187) to induce the acrosome reaction and acrosome reaction was evaluated. The results showed a significant effect of region with a higher percentage of tyrosine phosphorylation in spermatozoa from the cauda than in the caput or corpus regions (P=0.0061; P=0.0088). Spermatozoa from corpus and cauda showed higher values in the majority of the measured motility parameters than spermatozoa from the caput (P<0.0001). Spermatozoa from all epididymal regions can undergo the acrosome reaction in vitro in response to induction by calcium ionophore with no difference between regions (P>0.05). Spermatozoa from all epididymal regions were able to undergo capacitation. Higher percentage of tyrosine phosphorylation in spermatozoa from the cauda reflect that they more easily underwent capacitation compared to spermatozoa from caput and corpus which required more time of incubation for capacitation. In conclusion feline epididymal spermatozoa from all regions can undergo capacitation and acrosome reaction in vitro and do not require incubation under capacitating conditions. PMID- 26358919 TI - Rapidly Growing Pigmented Lesion in a 13-Year-Old Girl. PMID- 26358920 TI - Multiple Erythematous Papules in a Child with Neutropenia. PMID- 26358921 TI - Sclerodermoid Hypertrichotic Plaques with Insulin-Dependent Diabetes Mellitus. PMID- 26358922 TI - Heterochromia of the Scalp Hair Following Blaschko Lines: Four Cases. PMID- 26358924 TI - Erratum. PMID- 26358925 TI - Computing tools for implementing standards for single-case designs. AB - In the single-case design (SCD) literature, five sets of standards have been formulated and distinguished: design standards, assessment standards, analysis standards, reporting standards, and research synthesis standards. This article reviews computing tools that can assist researchers and practitioners in meeting the analysis standards recommended by the What Works Clearinghouse: Procedures and Standards Handbook-the WWC standards. These tools consist of specialized web based calculators or downloadable software for SCD data, and algorithms or programs written in Excel, SAS procedures, SPSS commands/Macros, or the R programming language. We aligned these tools with the WWC standards and evaluated them for accuracy and treatment of missing data, using two published data sets. All tools were tested to be accurate. When missing data were present, most tools either gave an error message or conducted analysis based on the available data. Only one program used a single imputation method. This article concludes with suggestions for an inclusive computing tool or environment, additional research on the treatment of missing data, and reasonable and flexible interpretations of the WWC standards. PMID- 26358926 TI - Activity-Directed Synthesis with Intermolecular Reactions: Development of a Fragment into a Range of Androgen Receptor Agonists. AB - Activity-directed synthesis (ADS), a novel discovery approach in which bioactive molecules emerge in parallel with associated syntheses, was exploited to develop a weakly binding fragment into novel androgen receptor agonists. Harnessing promiscuous intermolecular reactions of carbenoid compounds enabled highly efficient exploration of chemical space. Four substrates were prepared, yet exploited in 326 reactions to explore diverse chemical space; guided by bioactivity alone, the products of just nine of the reactions were purified to reveal diverse novel agonists with up to 125-fold improved activity. Remarkably, one agonist stemmed from a novel enantioselective transformation; this is the first time that an asymmetric reaction has been discovered solely on the basis of the biological activity of the product. It was shown that ADS is a significant addition to the lead generation toolkit, enabling the efficient and rapid discovery of novel, yet synthetically accessible, bioactive chemotypes. PMID- 26358927 TI - Invasive Squamous Cell Carcinoma in a Sternotomy Incision. PMID- 26358928 TI - Magnesium(I) Dimers Bearing Tripodal Diimine-Enolate Ligands: Proficient Reagents for the Controlled Reductive Activation of CO2 and SO2. AB - The first examples of magnesium(I) dimers bearing tripodal ligands, [(Mg{kappa(3) -N,N',O-(ArNCMe)2 (OCCPh2 )CH})2 ] [Ar=2,6-iPr2 C6 H3 (Dip) 7, 2,6-Et2 C6 H3 (Dep) 8, or mesityl (Mes) 9] have been prepared by post-synthetic modification of the beta-diketiminato ligands of previously reported magnesium(I) systems, using diphenylketene, O?C?CPh2 . In contrast, related reactions between beta diketiminato magnesium(I) dimers and the isoelectronic ketenimine, MesN?C?CPh2 , resulted in reductive insertion of the substrate into the Mg?Mg bond of the magnesium(I) reactant, and formation of [{(Nacnac)Mg}2 {MU-kappa(2) -N,C (Mes)NCCPh2 }] (Nacnac=[(ArNCMe)2 CH](-) ; Ar=Dep 10 or Mes 11). Reactions of the four-coordinate magnesium(I) dimer 8 with excess CO2 are readily controlled, and cleanly give carbonate [(LMg)2 (MU-kappa(2) :kappa(2) -CO3 )] 12 (L=[kappa(3) N,N',O-(DepNCMe)2 (OCCPh2 )CH](-) ; thermodynamic product), or oxalate [(LMg)2 (MU-kappa(2) :kappa(2) -C2 O4 )] 13 (kinetic product), depending on the reaction temperature. Compound 12 and CO are formed by reductive disproportionation of CO2 , whereas 13 results from reductive coupling of two molecules of the gas. Treatment of 8 with an excess of N2 O cleanly gives the MU-oxo complex [(LMg)2 (MU-O)] 14, which reacts facilely with CO2 to give 12. This result presents the possibility that 14 is an intermediate in the formation of 12 from the reaction of 8 and CO2 . In contrast to its reactions with CO2 , 8 reacts with SO2 over a wide temperature range to give only one product; the first example of a magnesium dithionite complex, [(LMg)2 (MU-kappa(2) :kappa(2) -S2 O4 )] 16, which is formed by reductive coupling of two molecules of SO2 , and is closely related to f-block metal dithionite complexes derived from similar SO2 reductive coupling processes. On the whole, this study strengthens previously proposed analogies between the reactivities of magnesium(I) systems and low-valent f-block metal complexes, especially with respect to small molecule activations. PMID- 26358929 TI - Assessing non-specific symptoms in epidemiological studies: Development and validation of the Symptoms and Perceptions (SaP) questionnaire. AB - OBJECTIVES: To describe the development of the Symptoms and Perceptions (SaP) questionnaire, a new instrument measuring diversity and severity features and related perceptions of non-specific (physical and psychological) symptoms (NSS) and to test its reliability and validity within an epidemiological setting. METHODS: First, a Delphi study was performed to develop the items of the questionnaire. Its psychometric properties were then tested within the context of an epidemiological study. This study yielded questionnaire data and general practice registry data from a sample of 5933 Dutch adults. Principal component analyses (PCA) were performed to test the factorial structure of the symptom assessment subscales of the SaP. Indicators of reliability and convergent validity were examined separately for the questionnaire parts of symptoms and perceptions. Criterion validity of the symptom scores of the SaP was also explored. RESULTS: The factorial structure of the symptom subscales reflected meaningful sets of clusters, indicative of the representation of all relevant organ systems. The SaP showed high reliability and good convergent validity for both the symptoms and perceptions part. It was also able to identify, to a certain degree, cases of diagnosed somatoform disorders and multiple NSS in primary care. Additionally, the scores on the "psychological" factor fairly predicted the diagnosis of common mental disorders. CONCLUSIONS: The SaP questionnaire is a reliable and valid self-reported measure of diverse features of NSS and corresponding perceptions. It can also be a useful tool for the identification of multiple somatic symptoms and related disorders in general practice and assessment of psychological problems in epidemiological studies. Further validation of the questionnaire in different samples and settings will establish the promising psychometric properties demonstrated in the present study. PMID- 26358930 TI - Circulating sclerostin and estradiol levels are associated with inadequate response to bisphosphonates in postmenopausal women with osteoporosis. AB - INTRODUCTION: The biological mechanisms associated with an inadequate response to treatment with bisphosphonates are not well known. This study investigates the association between circulating levels of sclerostin and estradiol with an inadequate clinical outcome to bisphosphonate therapy in women with postmenopausal osteoporosis. METHODS: This case-control study is based on 120 Spanish women with postmenopausal osteoporosis being treated with oral bisphosphonates. Patients were classified as adequate responders (ARs, n=66, mean age 68.2+/-8 years) without incident fractures during 5 years of treatment, or inadequate responders (IRs, n=54, mean age 67+/-9 years), with incident fractures between 1 and 5 years of treatment. Bone mineral density (DXA), structural analysis of the proximal femur and structural/fractal analysis of the distal radius were assessed. Sclerostin concentrations were measured by ELISA and 17beta estradiol levels by radioimmunoassay based on ultrasensitive methods. RESULTS: In the ARs group, sclerostin serum levels were significantly lower (p=0.02) and estradiol concentrations significantly higher (p=0.023) than in the IRs group. A logistic regression analysis was performed, including as independent variables in the original model femoral fracture load, 25 hydroxyvitamin D, previus history of fragility fracture, sclerostin and estradiol. Only previous history of fragility fracture (OR 14.04, 95% CI 2.38-82.79, p=0.004) and sclerostin levels (OR 1.11, 95% CI 1.02-1.20, p=0.011), both adjusted by estradiol levels remained associated with IRs. Also, sclerostin concentrations were associated with the index of resistance to compression (IRC) in the fractal analysis of the distal radius, a parameter on bone microstructure. CONCLUSIONS: Sclerostin and estradiol levels are associated with the response to bisphosphonate therapy in women with postmenopausal osteoporosis. PMID- 26358931 TI - Determinants of advanced stage presentation of breast cancer in 87,969 Brazilian women. AB - BACKGROUND: Breast cancer is commonly diagnosed at an advanced stage in Brazil. AIM: Analyze the determinants of advanced staging in Brazilian women with breast cancer. METHODS: Crosssectional study, including women diagnosed with breast cancer in Brazil, between 2000 and 2009. RESULTS: A total of 59,317 women were included, 53.5% being classified as advanced stage (>=IIB). Younger age (18 to 49 years old) (OR=1.61 95% CI 1.51 to 1.72) or between 40 and 49 years old (OR=1.08 95% CI 1.03 to 1.14), having low educational level (OR=1.53 95% CI 1.48 to 1.58), living in less developed geographical regions (OR=1.27 95% CI 1.21 to 1.33), having invasive ductal carcinoma (OR=2.70 95% CI 2.56 to 2.84) and invasive lobular carcinoma (OR=2.63 95% CI 2.42 to 2.86) were associated with advanced breast cancer. CONCLUSION: We conclude that future interventions should focus on these high risk groups. PMID- 26358932 TI - Bidirectional associations between circulating vitamin D and cholesterol levels: The Rotterdam Study. AB - OBJECTIVES: Higher levels of vitamin D have been associated with lower rates of cardiovascular disease perhaps through improved lipid profiles. However, results are inconsistent and the direction of the association between vitamin D and lipid levels remains unknown. We examined bidirectional associations between serum 25 hydroxyvitamin D (25(OH)D) and cholesterol concentrations. STUDY DESIGN: We used data from 1165 participants aged 55 to 88 years from the Rotterdam Study, a population-based prospective cohort study. MAIN OUTCOME MEASURES: Serum concentrations of 25(OH)D, total cholesterol (TC) and HDL cholesterol (HDL-C) were measured at two time points with a median time difference of 6 years. Bidirectional associations between 25(OH)D and each of the blood lipids was examined with path analyses in cross-lagged models. All models were adjusted for baseline age, sex, BMI, smoking status, and diet quality. RESULTS: The best-fit model for 25(OH)D and TC indicated that higher baseline TC concentrations were associated with lower 25(OH)D concentrations (standardized regression coefficient -0.05 (SE 0.02)), but 25(OH)D at baseline did not predict TC. For HDL-C, the best fit model suggested a bidirectional inverse association between HDL-C and 25(OH)D (standardized regression coefficients of -0.03 (SE 0.02)) for both directions. CONCLUSIONS: Our results from path analyses on repeatedly measured 25(OH)D and lipid levels suggest that total cholesterol may be associated with decreased in 25(OH)D concentrations, but not the other way around, whereas the observed inverse association between HDL-C and 25(OH)D may be bidirectional. PMID- 26358933 TI - Practice points in gynecardiology: Abnormal uterine bleeding in premenopausal women taking oral anticoagulant or antiplatelet therapy. AB - A growing number of premenopausal women are currently using antithrombotic and/or (dual) antiplatelet therapy for various cardiovascular indications. These may induce or exacerbate abnormal uterine bleeding and more awareness and knowledge among prescribers is required. Heavy and irregular menstrual bleeding is common in women in their forties and may have a variety of underlying causes that require different treatment options. Thus using anticoagulants in premenopausal women demands specific expertise and close collaboration between cardiovascular physicians and gynecologists. In this article we summarize the scope of the problem and provide practical recommendations for the care for young women taking anticoagulants and/or (dual) antiplatelet therapy. We also recommend that more safety data on uterine bleeding with novel anticoagulants in premenopausal women should be obtained. PMID- 26358934 TI - NMR assignments and structural characterization of new thiourea and urea kynurenamine derivatives nitric oxide synthase inhibitors. PMID- 26358935 TI - Palladium-Catalyzed Heteroarylation and Concomitant ortho-Alkylation of Aryl Iodides. AB - Three-component couplings were achieved from common aryl halides, alkyl halides, and heteroarenes under palladium and norbornene co-catalysis. The reaction forges hindered aryl-heteroaryl bonds and introduces ortho-alkyl groups to aryl rings. Various heterocycles such as oxazoles, thiazoles and thiophenes underwent efficient coupling. The heteroarenes were deprotonated in situ by bases without the assistance of palladium catalysts. PMID- 26358936 TI - Prediction of the substrate for nonribosomal peptide synthetase (NRPS) adenylation domains by virtual screening. AB - Nonribosomal peptide synthetases (NRPSs) synthesize a diverse array of bioactive small peptides, many of which are used in medicine. There is considerable interest in predicting NRPS substrate specificity in order to facilitate investigation of the many "cryptic" NRPS genes that have not been linked to any known product. However, the current sequence similarity-based methods are unable to produce reliable predictions when there is a lack of prior specificity data, which is a particular problem for fungal NRPSs. We conducted virtual screening on the specificity-determining domain of NRPSs, the adenylation domain, and found that virtual screening using experimentally determined structures results in good enrichment of the cognate substrate. Our results indicate that the conformation of the adenylation domain and in particular the conformation of a key conserved aromatic residue is important in determining the success of the virtual screening. When homology models of NRPS adenylation domains of known specificity, rather than experimentally determined structures, were built and used for virtual screening, good enrichment of the cognate substrate was also achieved in many cases. However, the accuracy of the models was key to the reliability of the predictions and there was a large variation in the results when different models of the same domain were used. This virtual screening approach is promising and is able to produce enrichment of the cognate substrates in many cases, but improvements in building and assessing homology models are required before the approach can be reliably applied to these models. PMID- 26358937 TI - Establishment of a novel human medulloblastoma cell line characterized by highly aggressive stem-like cells. AB - Medulloblastoma is a highly aggressive brain tumor and one of the leading causes of morbidity and mortality related to childhood cancer. These tumors display differential ability to metastasize and respond to treatment, which reflects their high degree of heterogeneity at the genetic and molecular levels. Such heterogeneity of medulloblastoma brings an additional challenge to the understanding of its physiopathology and impacts the development of new therapeutic strategies. This translational effort has been the focus of most pre clinical studies which invariably employ experimental models using human tumor cell lines. Nonetheless, compared to other cancers, relatively few cell lines of human medulloblastoma are available in central repositories, partly due to the rarity of these tumors and to the intrinsic difficulties in establishing continuous cell lines from pediatric brain tumors. Here, we report the establishment of a new human medulloblastoma cell line which, in comparison with the commonly used and well-established cell line Daoy, is characterized by enhanced proliferation and invasion capabilities, stem cell properties, increased chemoresistance, tumorigenicity in an orthotopic metastatic model, replication of original medulloblastoma behavior in vivo, strong chromosome structural instability and deregulation of genes involved in neural development. These features are advantageous for designing biologically relevant experimental models in clinically oriented studies, making this novel cell line, named USP-13-Med, instrumental for the study of medulloblastoma biology and treatment. PMID- 26358938 TI - Increased Body Mass Index Associated with Increased Risky Sexual Behaviors. AB - STUDY OBJECTIVE: The increasing prevalence of adolescent obesity has led to consideration of the potential effect of obesity on risky sexual behaviors. In the current study we examined whether body mass index (BMI) was related to age at sexual debut, type of sexual behavior, partner number, and condom use in a population of adolescent women at high risk for obesity and risky sexual behaviors. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional examination of 860 sexually active, predominantly minority, adolescent women who received medical care at an urban health center from 2007 through 2013. INTERVENTION AND MAIN OUTCOME MEASURES: Self-reported age at sexual debut, types of sexual intercourse, number of partners and condom use was compared with clinically assessed BMI. RESULTS: BMI was positively associated with number of sexual partners (P = .001) and history of attempted anal intercourse (P = .002). An inverse association was observed with age at first anal intercourse (P = .040). CONCLUSION: In this sample of adolescent women, increased BMI was associated with riskier sexual practices at a younger age. Results of this study suggest that overweight and obese adolescents are a vulnerable population who might need targeted sexual health counseling. PMID- 26358939 TI - Utility of the Oral Glucose Tolerance Test to Assess Glucose Abnormalities in Adolescents with Polycystic Ovary Syndrome. AB - STUDY OBJECTIVE: The aim of this study was to examine the prevalence of and risk factors for abnormal glucose metabolism in a large population of adolescents with polycystic ovary syndrome (PCOS). DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: A retrospective chart review was performed of 360 patients who presented to the pediatric gynecology outpatient clinic for evaluation of PCOS between January 2004 and May 2012. RESULTS: A total of 163 patients fulfilled criteria for a diagnosis of PCOS and had adequate clinical and laboratory data. Twenty-six adolescents (16.0%) had impaired glucose tolerance and 2 patients (1.2%) met criteria for a provisional diagnosis of type 2 diabetes. All 28 subjects with abnormal glucose metabolism were identified using the 2-hour plasma glucose of the oral glucose tolerance test. Conversely, the fasting glucose values only successfully detected 2 patients with hyperglycemia, both of whom also had abnormal 2-hour glucose levels. Adolescents with abnormal glucose metabolism were more likely to have reported a positive family history (P = .02) and had higher body mass index z scores (2.8 +/- 1.1 vs 1.8 +/- 1.2; P < .01). When patients were classified into normal weight (n = 29) and obese/overweight groups (n = 117), all of the patients with abnormal glucose metabolism were overweight or obese. CONCLUSION: In the largest series to date, we describe a prevalence of abnormal glucose metabolism in adolescent patients with PCOS of 17.2%. Abnormal glucose metabolism is associated with many of the known risk factors for metabolic syndrome. Our results support that the oral glucose tolerance test is a superior diagnostic test to assess abnormal glucose levels in overweight and obese adolescents but that this test might have limited utility in normal weight adolescents with PCOS. PMID- 26358941 TI - The conference. PMID- 26358940 TI - Recruiting family dyads facing thoracic cancer surgery: Challenges and lessons learned from a smoking cessation intervention. AB - PURPOSE: Persistent smoking after a cancer diagnosis has adverse effects. Most smoking cessation interventions focus on individual behaviors; however, family members who smoke are major barriers to success. This article describes challenges and lessons learned related to recruitment and retention to a longitudinal, dyadic-centered smoking cessation intervention study for individuals confronting a new diagnosis of thoracic cancer and their family members who smoke. METHODS: A prospective, one-group repeated measures, mixed method feasibility study measured recruitment, retention, adherence, and acceptability over a 6-month period in a thoracic surgery clinic at a university cancer center. A multidisciplinary, multi-component decision aid-"Tobacco Free Family"-was used to intervene with the dyads. Study recruitment occurred preoperatively with a thoracic surgery team member assessing smoking status. RESULTS: During the 6-month recruitment period, 50 patients who smoked were screened, and 18 eligible families were approached to participate. Sixteen participants (8 dyads) enrolled. Patients were all male, and participating family members were all female-either spouses or long-term girlfriends. Others types of family members declined participation. CONCLUSION: Recruitment was lower than anticipated (44%), retention was high (100%), and maximizing convenience was the most important retention strategy. Oncology nurses can assess the smoking status of patients and family members, facilitate understanding about the benefits of cessation, refer those willing to stop to expert resources, and help motivate those unwilling to quit. Research is needed to continue developing strategies to help patients with thoracic cancer and their families facing surgery as an impetus for stopping smoking. Novel intervention delivery and communication need further exploration. PMID- 26358942 TI - Plenary Sessions. PMID- 26358944 TI - Workshops. PMID- 26358945 TI - Scientific Programme. PMID- 26358946 TI - Poster Sessions. PMID- 26358947 TI - Copper-Mediated Formation of Aryl, Heteroaryl, Vinyl and Alkynyl Difluoromethylphosphonates: A General Approach to Fluorinated Phosphate Mimics. AB - A general and efficient access to aryl, heteroaryl, vinyl and alkynyl difluoromethylphosphonates is described. The developed methodology using TMSCF2PO(OEt)2, iodonium salts and a copper salt provided a straightforward manifold to reach these highly relevant products. The reaction proved to be highly functional group tolerant and proceeded under mild conditions, giving the corresponding products in good to excellent yields. This method represents the first general synthetic route to this important class of fluorinated scaffolds, which are well-recognized as in vivo stable phosphate surrogates. PMID- 26358948 TI - Bridging of partially negative atoms by hydrogen bonds from main-chain NH groups in proteins: The crown motif. AB - The backbone NH groups of proteins can form N1N3-bridges to delta-ve or anionic acceptor atoms when the tripeptide in which they occur orients them appropriately, as in the RL and LR nest motifs, which have dihedral angles 1,2 alphaR alphaL and 1,2-alphaL alphaR , respectively. We searched a protein database for structures with backbone N1N3-bridging to anionic atoms of the polypeptide chain and found that RL and LR nests together accounted for 92% of examples found (88% RL nests, 4% LR nests). Almost all the remaining 8% of N1N3 bridges were found within a third tripeptide motif which has not been described previously. We term this a "crown," because of the disposition of the tripeptide CO groups relative to the three NH groups and the acceptor oxygen anion, and the crown together with its bridged anion we term a "crown bridge." At position 2 of these structures the dihedral angles have a tight alphaR distribution, but at position 1 they have a wider distribution, with phi and psi values generally being lower than those at position 1. Over half of crown bridges involve the backbone CO group three residues N-terminal to the tripeptide, the remainder being to other main-chain or side-chain carbonyl groups. As with nests, bridging of crowns to oxygen atoms within ligands was observed, as was bridging to the sulfur atom of an iron-sulfur cluster. This latter property may be of significance for protein evolution. PMID- 26358949 TI - [Principles and fields of application of screening procedures]. AB - This article explains some important concepts of screening and early detection. It also discusses under which circumstances screening is useful, who can profit from screening and which persons may be at risk from screening procedures. Before the introduction of a screening program, empirical studies on the effectiveness are necessary to evaluate whether a screening program could be successful. PMID- 26358950 TI - Sonographic images of fetal terminal myelocystocele: a rare form of closed spinal dysraphism. PMID- 26358951 TI - Motor cortex rTMS improves dexterity in relapsing-remitting and secondary progressive multiple sclerosis. AB - The motor cortex (MC) receives an excitatory input from the cerebellum which is reduced in patients with cerebellar lesions. High-frequency repetitive transcranial magnetic stimulation (rTMS) induces cortical facilitation which can counteract the reduced cerebellar drive to the MC. Our study included 24 relapsing-remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS) patients with dysmetria. The patients were divided into two groups: Group A received two sessions of real MC rTMS and Group B received one session of real rTMS and one session of sham rTMS. Ten healthy volunteers formed group C. Evaluation was carried out using the nine-hole pegboard task and the cerebellar functional system score (FSS) of the expanded disability status scale (EDSS). Group A patients showed a significant improvement in the time required to finish the pegboard task (P = 0.002) and in their cerebellar FSS (P = 0.000) directly after the second session and 1 month later. The RRMS patients showed more improvement than the SPMS patients. Group B patients did not show any improvement in the pegboard task or the cerebellar FSS. These results indicate that MC rTMS can be a promising option in treating both RRMS or SPMS patients with cerebellar impairment and that its effect can be long-lasting. PMID- 26358952 TI - Longitudinally extensive transverse myelitis associated with amphiphysin autoimmunity and breast cancer: a paraneoplastic accompaniment. PMID- 26358953 TI - Could Big Data be the end of theory in science? A few remarks on the epistemology of data-driven science. PMID- 26358954 TI - Next generation partnerships in translational science and medicine: Partnerships between academics, big pharma, biotech firms, philanthropists and patients look set to change the way science advances. PMID- 26358955 TI - A holo'ome approach in colon cancer: we change as we age. PMID- 26358958 TI - Phoning in sick--telehealth in the iPhone age: As mobile devices become ubiquitous, can health care finally be delivered effectively over the Internet? PMID- 26358959 TI - Taphonomic alterations by the rodent species woodland vole (Microtus pinetorum) upon human skeletal remains. AB - This forensic case report describes the taphonomic effects of woodland vole (Microtus pinetorum) upon a set of skeletonized human remains recovered in Massachusetts, USA. Remains of an individual of this rodent species were discovered where it had been nesting inside the human cranium. Fine, parallel grooves indicative of small rodent gnawing were noted on multiple postcranial elements, and all isolated grooves were consistent in size with the incisors of this species. Other taphonomic alterations to these remains include some gnawing damage and dispersal by large carnivores. This case represents the first report of this rodent species affecting human remains. PMID- 26358957 TI - Plasticity of gene-regulatory networks controlling sex determination: of masters, slaves, usual suspects, newcomers, and usurpators. AB - Sexual dimorphism is one of the most pervasive and diverse features of animal morphology, physiology, and behavior. Despite the generality of the phenomenon itself, the mechanisms controlling how sex is determined differ considerably among various organismic groups, have evolved repeatedly and independently, and the underlying molecular pathways can change quickly during evolution. Even within closely related groups of organisms for which the development of gonads on the morphological, histological, and cell biological level is undistinguishable, the molecular control and the regulation of the factors involved in sex determination and gonad differentiation can be substantially different. The biological meaning of the high molecular plasticity of an otherwise common developmental program is unknown. While comparative studies suggest that the downstream effectors of sex-determining pathways tend to be more stable than the triggering mechanisms at the top, it is still unclear how conserved the downstream networks are and how all components work together. After many years of stasis, when the molecular basis of sex determination was amenable only in the few classical model organisms (fly, worm, mouse), recently, sex-determining genes from several animal species have been identified and new studies have elucidated some novel regulatory interactions and biological functions of the downstream network, particularly in vertebrates. These data have considerably changed our classical perception of a simple linear developmental cascade that makes the decision for the embryo to develop as male or female, and how it evolves. PMID- 26358960 TI - Public health challenges in the political economy of conflict: the case of Syria. AB - Recent uprisings in the Arab world and a full-scale war in Syria are widely viewed as popular demand for political voice against repressive regimes. However, growing economic inequalities and serious economic dysfunction played a role as trigger for conflict than is commonly accepted. Tunisia, Egypt and Syria all implemented policies of liberalization over the past two decades, leading to the worsening of living standards for the majority. The various forms of liberalization played a significant role in embedding social division and discontent whose outcomes affected other countries of the region with the onset of market reforms in nascent welfare states. Egypt, for example, was viewed by the World Bank as an economic 'best performer', despite regular riots over food prices, job losses and land expropriation for tourism. Tunisia was praised by donors just prior to the uprising (in 2010), for 'weathering well' the global economic downturn through 'sound macroeconomic management'. In Syria, the market economy made its mark over the 90s, but macroeconomic adjustment policies were implemented in a bilateral agreement with the European Union and approved by the International Monetary Fund in 2003. The economic stabilization programme that followed had limited concern for social impacts such as jobs losses, price rises and national debt, which ultimately caused immense hardship for the population at large, acting as a trigger for the initial uprising in 2011, prior to its transformation into a fully blown conflict. This article focuses on reforms implemented in the health sector and sets these in the context of the current political economy of Syria. It suggests that a protective approach to public health services during and in the aftermath of conflict may increase the possibilities of reconstruction and reconciliation between warring sides. PMID- 26358956 TI - New frontiers: discovering cilia-independent functions of cilia proteins. AB - In most vertebrates, mitotic spindles and primary cilia arise from a common origin, the centrosome. In non-cycling cells, the centrosome is the template for primary cilia assembly and, thus, is crucial for their associated sensory and signaling functions. During mitosis, the duplicated centrosomes mature into spindle poles, which orchestrate mitotic spindle assembly, chromosome segregation, and orientation of the cell division axis. Intriguingly, both cilia and spindle poles are centrosome-based, functionally distinct structures that require the action of microtubule-mediated, motor-driven transport for their assembly. Cilia proteins have been found at non-cilia sites, where they have distinct functions, illustrating a diverse and growing list of cellular processes and structures that utilize cilia proteins for crucial functions. In this review, we discuss cilia-independent functions of cilia proteins and re-evaluate their potential contributions to "cilia" disorders. PMID- 26358961 TI - Energy Migration Upconversion in Manganese(II)-Doped Nanoparticles. AB - We report the synthesis and characterization of cubic NaGdF4:Yb/Tm@NaGdF4:Mn core shell structures. By taking advantage of energy transfer through Yb->Tm->Gd->Mn in these core-shell nanoparticles, we have realized upconversion emission of Mn(2+) at room temperature in lanthanide tetrafluoride based host lattices. The upconverted Mn(2+) emission, enabled by trapping the excitation energy through a Gd(3+) lattice, was validated by the observation of a decreased lifetime from 941 to 532 MUs in the emission of Gd(3+) at 310 nm ((6)P(7/2)->(8)S(7/2)). This multiphoton upconversion process can be further enhanced under pulsed laser excitation at high power densities. Both experimental and theoretical studies provide evidence for Mn(2+) doping in the lanthanide-based host lattice arising from the formation of F(-) vacancies around Mn(2+) ions to maintain charge neutrality in the shell layer. PMID- 26358962 TI - GABA modulates baroreflex in the ventral tegmental area in rat. AB - There are some reports demonstrating the cardiovascular functions of the ventral tegmental area (VTA). About 20-30% of the VTA neurons are GABAergic, which might play a role in baroreflex modulation. This study was performed to find the effects of GABA(A), GABA(B) receptors and reversible synaptic blockade of the VTA on baroreflex. Drugs were microinjected into the VTA of urethane anesthetized rats, and the maximum change of blood pressure and the gain of the reflex bradycardia in response to intravenous phenylephrine (Phe) injection were compared with the preinjection and the control values. Microinjection of bicuculline methiodide (BMI, 100 pmol/100 nl), a GABA(A) antagonist, into the VTA strongly decreased the Phe-induced hypertension, indicating that GABA itself attenuated the baroreflex. Muscimol, a GABA(A) agonist (30 mM, 100 nl), produced no significant changes. Baclofen, a GABA(B) receptor agonist (1000 pmole/100 nl), moderately attenuated the baroreflex, however phaclofen, a GABA(B) receptor antagonist (1000 pmole/100 nl), had no significant effect. In conclusion, for the first time, we demonstrated that GABA(A) receptors of the VTA strongly attenuate and GABA(B) receptors of the VTA moderately attenuate baroreflex in rat. PMID- 26358963 TI - Effects of chemical elements in the trophic levels of natural salt marshes. AB - The relationships between the bioaccumulation of Na, K, Ca, Mg, Fe, Zn, Cu, Mn, Co, Cd, and Pb, acidity (pH), salinity (Ec), and organic matter content within trophic levels (water-soil-plants-invertebrates) were studied in saline environments in Poland. Environments included sodium manufactures, wastes utilization areas, dumping grounds, and agriculture cultivation, where disturbed Ca, Mg, and Fe exist and the impact of Cd and Pb is high. We found Zn, Cu, Mn, Co, and Cd accumulation in the leaves of plants and in invertebrates. Our aim was to determine the selectivity exhibited by soil for nutrients and heavy metals and to estimate whether it is important in elucidating how these metals are available for plant/animal uptake in addition to their mobility and stability within soils. We examined four ecological plant groups: trees, shrubs, minor green plants, and water macrophytes. Among invertebrates, we sampled breastplates Malacostraca, small arachnids Arachnida, diplopods Diplopoda, small insects Insecta, and snails Gastropoda. A higher level of chemical elements was found in saline polluted areas (sodium manufactures and anthropogenic sites). Soil acidity and salinity determined the bioaccumulation of free radicals in the trophic levels measured. A pH decrease caused Zn and Cd to increase in sodium manufactures and an increase in Ca, Zn, Cu, Cd, and Pb in the anthropogenic sites. pH increase also caused Na, Mg, and Fe to increase in sodium manufactures and an increase in Na, Fe, Mn, and Co in the anthropogenic sites. There was a significant correlation between these chemical elements and Ec in soils. We found significant relationships between pH and Ec, which were positive in saline areas of sodium manufactures and negative in the anthropogenic and control sites. These dependencies testify that the measurement of the selectivity of cations and their fluctuation in soils provide essential information on the affinity and binding strength in these environments. The chemical elements accumulated in soils and plants; however, further flow is selective and variable. The selectivity exhibited by soil systems for nutrients and heavy metals is important in elucidating how these metals become available for plant/animal uptake and also their mobility and stability in soils. PMID- 26358966 TI - Seventeen-Year-Old Male With Gross Hematuria. PMID- 26358965 TI - Quality of life assessment in domestic dogs: An evidence-based rapid review. AB - Assessment of quality of life (QoL) is an important, increasingly popular outcome measure in veterinary research and practice, particularly in dogs. In humans, QoL is commonly assessed by self-reporting and since this is not possible for animals, it is crucial that instruments designed to measure QoL are tested for reliability and validity. Using a systematic, replicable literature search strategy, the aim of this study was to find published, peer-reviewed instruments for QoL assessment in dogs and to assess the quality of these. CAB Abstracts and PubMed were searched in July 2013 using terms relevant to dogs, wellbeing and QoL. Inclusion and exclusion criteria were applied. When instruments were not published in full, authors were contacted to obtain them. Criteria were applied to assess the quality, validity and reliability of the 52 instruments obtained. Twenty-seven additional instruments used in peer-reviewed publications were not included because they had not been fully described in the publication or were not provided by authors upon request. Most of the instruments reviewed (48/52) were disease-specific rather than generic. Only four publications provided a definition of QoL or wellbeing. Only 11/52 instruments demonstrated evidence of assessing reliability or validity, and the quality of these instruments was variable. Many novel, unvalidated instruments have been generated and applied as clinical outcomes before it was known whether they measured QoL. This rapid review can be used to identify currently available and validated canine QoL instruments, and to assess the validity and quality of new or existing instruments. PMID- 26358967 TI - A 5-Year-Old Female With Short Stature. PMID- 26358968 TI - Ability of physicians to diagnose influenza and usefulness of a rapid influenza antigen test in febrile returning travelers: A randomized controlled trial. AB - BACKGROUND: Fever is a frequent cause of medical consultation among returning travelers. The objectives of this study were to assess whether physicians were able to identify patients with influenza and whether the use of an influenza rapid diagnostic test (iRDT) modified the clinical management of such patients. METHODS: Randomized controlled trial conducted at 2 different Swiss hospitals between December 2008 and November 2012. Inclusion criteria were 1) age >= 18 years, 2) documented fever of >= 38 degrees C or anamnestic fever + cough or sore throat within the last 4 days, 3) illness occurring within 14 days after returning from a trip abroad, 4) no definitive alternative diagnosis. Physicians were asked to estimate the likelihood of influenza on clinical grounds, and a single nasopharyngeal swab was taken. Thereafter patients were randomized into 2 groups: i) patients with iRDT (BD Directigen A + B) performed on the nasopharyngeal swab, ii) patients receiving usual care. A quantitative PCR to detect influenza was done on all nasopharyngeal swabs after the recruitment period. Clinical management was evaluated on the basis of cost of medical care, number of X-rays requested and prescription of anti-infective drugs. RESULTS: 100 eligible patients were referred to the investigators. 93 patients had a naso pharyngeal swab for a PCR and 28 (30%) swabs were positive for influenza. The median probability of influenza estimated by the physician was 70% for the PCR positive cases and 30% for the PCR negative cases (p < 0.001). The sensitivity of the iRDT was only 20%, and specificity 100%. Mean medical cost for the patients managed with iRDT and without iRDT were USD 581 (95%CI 454-707) and USD 661 (95%CI 522-800) respectively. 14/60 (23%) of the patients managed with iRDT were prescribed antibiotics versus 13/33 (39%) in the control group (p = 0.15). No patient received antiviral treatment. CONCLUSION: Influenza was a frequent cause of fever among these febrile returning travelers. Based on their clinical assessment, physicians had a higher level of suspicion for influenza in PCR positive cases. The iRDT used in this study showed a disappointingly low sensitivity and can therefore not be recommended for the management of these patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT00821626. PMID- 26358969 TI - Is the introduction of an accreditation program likely to generate organization wide quality, change and learning? AB - OBJECTIVE: This research assesses whether integration of Accreditation Canada's program brings about change and organizational learning. METHODS: Two health organizations, the Health Authority of Anguilla and the Ca' Foncella Opetale di Treviso, are studied on three levels: (1) members; (2) accreditation teams; and (3) organization. The methods used to collect data consisted of individual questionnaires administered to team members, semi-formal interviews with team leaders and quality coordinators, a documentation review and periodic assessments of compliance with the standards. RESULTS: The findings indicate that the organizations made strategic, organizational and relational changes. They improved their systems and management practices as well as their internal and external communications. There was also useful learning by individuals, teams and the organizations. Individual learning involved quality practice, client-focused approach, risk management, ethics, participatory management and assessment of services. The "self-assessment" and "make improvements and follow up on recommendations" stages of the accreditation cycle contributed the most to change and organizational learning. The interdisciplinary accreditation teams were the preferred vehicle for achieving these changes and this learning. CONCLUSIONS: The Health Authority of Anguilla and Ca' Foncella Opetale di Treviso have gradually improved their level of compliance with the standards in all quality dimensions. However, improvement in the overall compliance level was below the program's minimum requirements to obtain accreditation status without major restrictions. The scope of the changes and learning achieved raises the issue of the capacity of organizations to formalize this new knowledge throughout the organization. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26358970 TI - Five-year trends for ventilator-associated pneumonia: Correlation between microbiological findings and antimicrobial drug consumption. AB - The epidemiology of multidrug-resistant bacteria (MDRB) has changed significantly in European healthcare settings, with a decrease in frequency of meticillin resistant Staphylococcus aureus and an increase in extended-spectrum beta lactamase (ESBL)-producing Enterobacteriaceae. Little is known about the effects of these changes on ventilator-associated pneumonia (VAP). A retrospective 5-year trend analysis of ICU antibiotic consumption and resistance in bacteria causing VAP was undertaken. Poisson regression analysis between complete microbiological data and antibiotic consumption was performed. In total, 252 episodes of VAP in 184 patients were identified between 2007 and 2011, from which 364 causal bacteria were isolated. Enterobacteriaceae isolation rates increased significantly over this period [from 6.64 to 10.52 isolates/1000 patient-days; P=0.006], mostly due to an increase in AmpC-producing Enterobacteriaceae (APE) (2.85-4.51 isolates/1000 patient-days; P=0.013), whereas the number of episodes due to S. aureus and Pseudomonas aeruginosa remained stable. A positive association was found between the increase in APE infections and an increase in past-year antibiotic consumption: amoxicillin/clavulanic acid (P=0.003), ceftazidime and cefepime (P=0.007), carbapenems (P=0.002), fluoroquinolones (P=0.012), macrolides (P=0.002) and imidazoles (P=0.004). No such association was found for the emergence of resistance in P. aeruginosa. These results indicate a change in the epidemiology of VAP, with Enterobacteriaceae exceeding P. aeruginosa and S. aureus. Moreover, a positive correlation was observed between antibiotic consumption and the incidence of potentially MDRB such as APE. No such correlation was found for ESBL-producing Escherichia coli and antibiotic resistant P. aeruginosa. PMID- 26358971 TI - In vivo efficacy of voriconazole and posaconazole therapy in a novel invertebrate model of Aspergillus fumigatus infection. AB - The emergence of azole resistance in Aspergillus fumigatus is a clinically important issue in the management of invasive aspergillosis as it could limit therapeutic options. Accurate measurement of in vitro antifungal activity in terms of minimum inhibitory concentration (MIC) is considered of clinical relevance and often gives useful therapeutic information for physicians. However, the lack of in vitro-in vivo correlation is frequent and the observed in vitro phenotype does not always correlate with the in vivo response. In this regard, a wild-type strain and five A. fumigatus cyp51A mutated strains showing different azole susceptibility profiles were used to investigate whether the greater wax moth (Galleria mellonella) is an alternative model to assess the in vivo efficacy of voriconazole and posaconazole. Administration of both azoles improved the survival of larvae infected with susceptible strains. However, those larvae infected with resistant strains did not respond to treatment. The phenotype observed in vitro was found to correlate with the efficacy observed in vivo. Moreover, using this in vivo model, the pharmacodynamic target predicting therapeutic success (AUC(0-24)/MIC) was in the same range as previously described, allowing the use of the G. mellonella model to predict the azole susceptibility profile of A. fumigatus strains. PMID- 26358972 TI - Erratum to: Antibiotic use varies substantially among adults: a cross-national study from five European Countries in the ARITMO project. PMID- 26358973 TI - Biotinidase deficiency should be considered in individuals exhibiting myelopathy with or without and vision loss. AB - Multiple symptomatic children with biotinidase deficiency have exhibited spastic para- or tetraplegia due to myelopathy with and without vision loss. Although this has been a feature of what has been designated as delayed onset-biotinidase deficiency, myelopathy is likely also on the continuum of clinical features seen in younger children who have had these features attributed to dysfunction of the upper brain rather than of the spinal cord. Because many countries are still not screening their newborns for biotinidase deficiency, the disorder should be included in the differential diagnosis of individuals with myelopathic symptoms. Many of these children have gone weeks to months before they were correctly diagnosed with biotinidase deficiency. Rapid recognition that a child with myelopathy with and without vision loss has biotinidase deficiency will undoubtedly facilitate prompt treatment, increase the possibility of complete recovery and avoid potential residual permanent neurological damage. Newborn screening for biotinidase deficiency would avoid the delay in the diagnosis and treatment of individuals who otherwise may present with myelopathic or other neurological symptoms. PMID- 26358974 TI - Determinants of physician's office visits and potential effects of co-payments: evidence from Austria. AB - OBJECTIVE: The objective of this study is to analyse determinants of physician office visits and potential effects of co-payments in Austria. METHODS: Based on survey data, the number of annual physician office visits is regressed on a set of explanatory variable such as income, communication behaviour in waiting room, travel time, gender, age, presence of chronic diseases and connectedness to family members. It was then examined how those determinants are affected by hypothetical co-payments in the range of ?5 to ?200. RESULTS: Our results suggest a negative impact of income and family connectedness on doctor's visits. On the other hand, age, morbidity and active communication behaviour in the waiting room are positively associated with office visits. The significant impact of both income and active communication behaviour on the number of doctor's visits disappears when significant co-payments greater than ?50 are introduced. CONCLUSIONS: Higher co-payments would reduce healthcare service utilization in Austria mainly because of a demand reduction of poorer patients. Another key finding of our study is that the desire to chat with peers in the waiting room is another significant driver of physician office visits. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26358976 TI - Orbital fractures in the emergency department: a review of early assessment and management. AB - Orbital fractures are a common, potentially vision-threatening presentation to an emergency department. Appropriate early management and referral by the emergency medicine practitioner has a significant role in preventing cosmetic and functional sequelae of orbital trauma. In this paper, we review the emergency, non-specialist management of traumatic injuries to the orbit. PMID- 26358975 TI - Comparison of obese adults with poor versus good sleep quality during a functional neuroimaging delay discounting task: A pilot study. AB - This study aimed to determine if obese adults with poor versus good sleep quality demonstrate reduced self-regulatory capacity and different patterns of neural activation when making impulsive monetary choices. Six obese, good quality sleepers (M age=44.7 years, M BMI=38.1 kg/m(2)) were compared to 13 obese, poor quality sleepers (M age=42.6, M BMI=39.2 kg/m(2)) on sleep and eating behavior and brain activation in prefrontal and insular regions while engaging in a delay discounting task during functional magnetic resonance imaging (fMRI). Poor quality sleepers demonstrated significantly lower brain activation in the right inferior frontal gyrus, right middle frontal gyrus, and bilateral insula when making immediate and smaller (impulsive) monetary choices compared to the baseline condition. Behaviorally, poor compared to good quality sleepers reported higher scores in the night eating questionnaire. Obese adults with poor sleep quality demonstrate decreased brain activation in multiple regions that regulate cognitive control and interceptive awareness, possibly reducing self-regulatory capacity when making immediately gratifying decisions. PMID- 26358977 TI - Discussing dissection in anatomy education. PMID- 26358978 TI - Developing students' teaching through peer observation and feedback. AB - With the increasing popularity and scale of peer teaching, it is imperative to develop methods that ensure the quality of teaching provided by undergraduate students. We used an established faculty development and quality assurance process in a novel context: peer observation of teaching for undergraduate peer tutors. We have developed a form to record observations and aid the facilitation of feedback. In addition, experienced peer tutors have been trained to observe peer-taught sessions and provide tutors with verbal and written feedback. We have found peer observation of teaching to be a feasible and acceptable process for improving quality of teaching provided by undergraduate medical students. However, feedback regarding the quality of peer observer's feedback may help to develop students' abilities further. PMID- 26358979 TI - Too much control diverts from the essence of learning and teaching. PMID- 26358980 TI - Probing structural and motional features of organic and inorganic solids through extended family of cross-polarization experiments. AB - Combined use of cross-polarization and magic-angle spinning in the middle of the seventies has opened a new era of high-resolution solid-state NMR spectroscopy. Cross-polarization procedure is commonly used to obtain a shorter measuring time and to investigate or exploit one nucleous by means of the other nucleous involved in the polarization transfer. An extended family of cross-polarization experiments including constant time cross-polarization approach, cross polarization inversion and indirect observation of proton spin system is reviewed and illustrated with applications to a large range of solids. PMID- 26358981 TI - An optimal double-magic flip angle for performing the distance measurement REDOR experiment on a spin S=1. AB - Distance measurements between a half-spin and a quadrupolar S=1 spin having a small quadrupolar coupling constant can be performed using the rotational echo double resonance (REDOR) experiment. We derived an analytical expression for the probability of transitions between energy levels resulting from the application of an arbitrary pulse flip angle to the quadrupolar spin and consequently minimized the probability that populations of individual levels do not undergo a spin transition during the pulse. As a result we discovered that if the flip angle of the quadrupolar spin pulse is 109.47 degrees , the maximal recoupling values are the largest possible and the signal reaches a maximum value of 8/9, larger than in the use of either a 90 degrees pulse or a 180 degrees pulse. In addition, the slope of the initial decay is higher than that of the 90 degrees pulse. The recoupling signal can be modeled by an exact analytical formula in the ideal case and simulations show that the advantage of the 109.47 degrees pulse is preserved when the quadrupolar coupling constant CQ has a finite value typical of (2)H and (6)Li spins (up to CQ~200kHz). Experimental results on two spin pairs, (2)H-(13)C and (6)Li-(13)C, demonstrate the validity and accuracy of this method. PMID- 26358982 TI - [Adaptive radiotherapy in routine use? State of the art: The medical physicist's point of view]. AB - The development of both image-guided and intensity-modulated radiotherapy has underlined the question of treatment adaptation to anatomical and/or biological changes occurring during radiotherapy course and modifying delivered dose to the patient. Adaptive radiotherapy has been introduced when several plans are used to treat a patient during radiotherapy. Adaptation may be performed online, offline or in a hybrid way. New images of the patient are needed for adaptive radiotherapy to perform many processes: image registration, segmentation and evaluation of cumulative dose. Deformable image registration methods are generally used to image registration and contours propagation. Fraction and cumulative dose evaluations use deformable image registration methods or more complex methods based on Monte-Carlo calculation. These methods have uncertainties and have to be evaluated. However, evaluation and validation tools are still being developed. The physicist's mission is to ensure that every new technology, such as adaptive radiotherapy, is deployed with highest safety, by technical validation and by implementing a specific quality assurance program. Adaptive radiotherapy implementation still raises many questions, so its potential clinical application requires great caution and should be carefully explored in prospective clinical trials. PMID- 26358983 TI - [Lung cancer: Stereotactic body radiation therapy and surgery]. AB - Stereotactic body radiation therapy for lung cancer is now well established for patients who are not eligible to surgery. These patients can benefit from a curative treatment, which is a new therapeutic indication. Protocols are effective and well tolerated even for the most fragile patients. Three randomized trials comparing stereotactic body radiation therapy and surgery failed due to poor accrual. However, taking into account the favourable available data, the choice of stereotactic body radiation therapy in first intention arises. The treatment decision has to be discussed in a multidisciplinary way, while considering the opinion of the patient, who must be clearly informed about the principle of both therapeutic options. PMID- 26358984 TI - Reply to the letter concerning the published article entitled "Using combinatorial bioinformatics methods to analyze annual perspective changes of influenza viruses and to accelerate development of effective vaccines". PMID- 26358986 TI - In Memoriam: Professor Laurentiu M. Popescu (1944-2015). PMID- 26358985 TI - Vasodilator-stimulated phosphoprotein restricts cell-to-cell spread of Shigella flexneri at the cell periphery. AB - Shigella spp. are intracellular bacterial pathogens that cause diarrhoeal disease in humans. Shigella utilize the host actin cytoskeleton to enter cells, move through the cytoplasm of cells and pass into adjacent cells. Ena/VASP family proteins are highly conserved proteins that participate in actin-dependent dynamic cellular processes. We tested whether Ena/VASP family members VASP (vasodilator-stimulated phosphoprotein), Mena (mammalian-enabled) or EVL (Ena VASP-like) contribute to Shigella flexneri spread through cell monolayers. VASP and EVL restricted cell-to-cell spread without significantly altering actin-based motility, whereas Mena had no effect on these processes. Phosphorylation of VASP on Ser153, Ser235 and Thr274 regulated its subcellular distribution and function. VASP derivatives that lack the Ena/VASP homology 1 (EVH1) domain or contain a phosphoablative mutation of Ser153 were defective in restricting S. flexneri spread, indicating that the EVH1 domain and phosphorylation on Ser153 are required for this process. The EVH1 domain and Ser153 of VASP were required for VASP localization to focal adhesions, and localization of VASP to focal adhesions and/or the leading edge was required for restriction of spread. The contribution of the EVH1 domain was from both the donor and the recipient cell, whereas the contribution of Ser153 phosphorylation was only from the donor cell. Thus, unlike host proteins characterized in Shigella pathogenesis that promote bacterial spread, VASP and EVL function to limit it. The ability of VASP and EVL to limit spread highlights the critical role of focal adhesion complexes and/or the leading edge in bacterial passage between cells. PMID- 26358987 TI - Ontogenetic shifts and spatial associations in organ positions for snakes. AB - Snakes possess an elongated body form and serial placement of organs which provides the opportunity to explore historic and adaptive mechanisms of organ position. We examined the influence of body size and sex on the position of, and spatial associations between, the heart, liver, small intestine, and right kidney for ten phylogenetically diverse species of snakes that vary in body shape and habitat. Snake snout-vent length explained much of the variation in the position of these four organs. For all ten species, the position of the heart and liver relative to snout-vent length decreased as a function of size. As body size increased from neonate to adult, these two organs shifted anteriorly an average of 4.7% and 5.7% of snout-vent length, respectively. Similarly, the small intestine and right kidney shifted anteriorly with an increase in snout-vent length for seven and five of the species, respectively. The absolute and relative positioning of these organs did not differ between male and female Burmese pythons (Python molurus). However, for diamondback water snakes (Nerodia rhombifer), the liver and small intestine were more anteriorly positioned in females as compared to males, whereas the right kidney was positioned more anteriorly for males. Correlations of residuals of organ position (deviation from predicted position) demonstrated significant spatial associations between organs for nine of the ten species. For seven species, individuals with hearts more anterior (or posterior) than predicted also tended to possess livers that were similarly anteriorly (or posteriorly) placed. Positive associations between liver and small intestine positions and between small intestine and right kidney positions were observed for six species, while spatial associations between the heart and small intestine, heart and right kidney, and liver and right kidney were observed in three or four species. This study demonstrates that size, sex, and spatial associations may have potential interacting effects when testing evolutionary scenarios for the position of snake organs. PMID- 26358988 TI - Plasticity in fecundity highlights the females' importance in the spiny-cheek crayfish invasion mechanism. AB - Invasion is one of the most consequential phenomena affecting the distribution of native species. Few in number of species, European crayfish are losing the competition with introduced North American crayfish. The spiny-cheek crayfish, Orconectes limosus, is an outstanding example, successfully competing against the native narrow-clawed crayfish, Astacus leptodactylus. For four years, we collected data regarding crayfish occurrences, their relative abundance, and the structure of populations in the ongoing colonisation process of O. limosus in the lower Danube. The mature females of both invasive and indigenous crayfish species were analysed with respect to biometry and production of oocytes in relation to the dynamics of invasion. The interspecific comparisons showed no significant differences regarding body size, with an average of approximately 102 mm total length and 31 g wet weight for both species. However, the fecundity of the indigenous species was found to be constant throughout the investigated area, whereas the number of eggs produced by the invasive females was significantly increased at the active front of the invasion. The maximum number of ovarian eggs found was 887 and 1156 in the indigenous species and the invasive species, respectively. We propose the scenario that the invasive species, which carries the deadly crayfish plague, creates an ecological advantage by reducing the populations of indigenous crayfish. Subsequently, the invasive females opportunistically use the available resources to enhance their fecundity, resulting in the acute growth of populations. However, the long-term competitiveness and colonisation success of O. limosus still remain in question. PMID- 26358989 TI - Strong spatial segregation between wildcats and domestic cats may explain low hybridization rates on the Iberian Peninsula. AB - The European wildcat (Felis silvestris silvestris) is an endangered felid impacted by genetic introgression with the domestic cat (Felis silvestris catus). The problem of hybridization has had different effects in different areas. In non Mediterranean regions pure forms of wildcats became almost extinct, while in Mediterranean regions genetic introgression is a rare phenomenon. The study of the potential factors that prevent the gene flow in areas of lower hybridization may be key to wildcat conservation. We studied the population size and spatial segregation of wildcats and domestic cats in a typical Mediterranean area of ancient sympatry, where no evidence of hybridization had been detected by genetic studies. Camera trapping of wild-living cats and walking surveys of stray cats in villages were used for capture-recapture estimations of abundance and spatial segregation. Results showed (i) a low density of wildcats and no apparent presence of putative hybrids; (ii) a very low abundance of feral cats in spite of the widespread and large population sources of domestic cats inhabiting villages; (iii) strong spatial segregation between wildcats and domestic/feral cats; and (iv) no relationship between the size of the potential population sources and the abundance of feral cats. Hence, domestic cats were limited in their ability to become integrated into the local habitat of wildcats. Ecological barriers (habitat preferences, food limitations, intra-specific and intra-guild competition, predation) may explain the severe divergences of hybridization impact observed at a biogeographic level. This has a direct effect on key conservation strategies for wildcats (i.e., control of domestic cats). PMID- 26358990 TI - Validity and reliability of the HeartQoL questionnaire in a large sample of stable coronary patients: The EUROASPIRE IV Study of the European Society of Cardiology. AB - BACKGROUND: The aim of this study was to investigate the validity and reliability of the HeartQoL instrument in a population of stable coronary patients. DESIGN: Analyses are based on the cross-sectional EUROASPIRE IV (EUROpean Action on Secondary and Primary prevention through Intervention to Reduce Events) survey. METHODS: Patients with a diagnosis of coronary heart disease were examined and interviewed 6 months to 3 years after their coronary event. During the interview patients were asked to fill out the HeartQoL health-related quality of life questionnaire as well as the EQ-5D and the hospital anxiety and depression scale questionnaire. Psychometric analyses assessing the reliability and validity of the HeartQoL instrument were performed. RESULTS: A total of 7449 patients completed the HeartQoL instrument. Cronbach's alpha indicated excellent internal consistency for the global HeartQoL scale (alpha = 0.92) and the physical subscale (alpha = 0.91) and good internal consistency for the emotional subscale (alpha = 0.87). Factor analysis confirmed the two-dimensional construct although mixed results were found regarding the model fit. Discriminative validity analysis confirmed better HeartQoL results in men, younger patients and higher educated persons. Likewise, convergent validity was confirmed with moderate to strong correlations among hypothesised constructs. CONCLUSION: Overall, psychometric analyses of the HeartQoL instrument in a population of patients with stable coronary heart disease showed good reliability and validity both at the European as well as the country-specific level. However, further research should focus on the responsiveness of the HeartQoL, the possible ceiling effect of the emotional subscale, construct validity and the minimal clinically important difference. PMID- 26358991 TI - The combined exercise stress echocardiography and cardiopulmonary exercise test for identification of masked heart failure with preserved ejection fraction in patients with hypertension. AB - BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is commonly associated with hypertension (HTN). However, resting echocardiography (ECHO) can underestimate the severity of disease. Exercise stress echocardiography (ESE) and the cardiopulmonary exercise testing (CPX) appeared to be useful tests in dynamic assessment of HFpEF. The value of combined exercise stress echocardiography cardiopulmonary testing (ESE-CPX) in the identification of masked HFpEF is still undetermined. OBJECTIVE: The purpose of this study was to analyse the value of the combined ESE-CPX in the identification of masked HFpEF in patients with HTN, dyspnoea and normal resting left ventricular (LV) systolic and diastolic function. METHODOLOGY: We studied 87 patients with HTN, exertional dyspnoea and normal resting LV function. They all underwent ESE-CPX testing (supine bicycle, ramp protocol, 15 W/min). ECHO measurements were performed at rest, and at peak load. Achievement of peak E/e' ratio>15 was a marker for masked HFpEF. RESULTS: Increase of E/e'>15 occurred in 8/87 patients (9.2%) during ESE-CPX. Those patients had the lower peak VO2 (p = 0.012), the lower VO2 at anaerobic threshold (p = 0.025), the lower workload (p = 0.026), the lower peak partial pressure end tidal carbon dioxide (PetCO2) (p < 0.0001), and the higher VE/VCO2 slope (p < 0.0001) which was an independent multivariate predictor of HFpEF (p = 0.021), with the cut-off value of 32.95 according to the receiver-operator characteristic (ROC) curve (sensitivity (Sn) 100%, specificity (Sp) 90%). CONCLUSION: The combined ESE-CPX test is feasible and reliable test that can unmask HFpEF and may become an important aid in the early diagnosis of HFpEF, excluding the other causes of exertional dyspnoea. PMID- 26358993 TI - Using Performance Status to Guide Initiation of Palliative Care Support among Patients with Cancer. PMID- 26358992 TI - The association of albuminuria and high-sensitivity C-reactive protein with the efficacy of HMG-coenzyme A reductase inhibitors for cardiovascular event prevention. AB - BACKGROUND: It is not clear which hypercholesterolemic patients benefit most from beta-hydroxy-beta-methylglutaryl coenzyme A reductase inhibitors with respect to the prevention of cardiovascular events. Early signs of atherosclerotic vascular damage may identify high-risk patients. DESIGN: We studied whether subjects with hypercholesterolemia will benefit more from starting statin treatment in the case of high albuminuria and/or high-sensitivity C-reactive protein (hsCRP). METHODS: Included were subjects who had hypercholesterolemia at baseline, a negative cardiovascular disease history and who were not treated with statins. In total, 2011 subjects were analysed, of whom 695 started with a statin during a follow-up of 7.0 +/- 1.7 years. Adjusted hazard ratios (HRs) for cardiovascular events were calculated in subjects who started versus those who did not start a statin stratified for albuminuria less than or >= 15 mg/day and/or hsCRP less than or >= 3 mg/L. RESULTS: The start of a statin was associated with a beneficial effect on cardiovascular risk in subjects with high albuminuria (HR 0.38 (0.23-0.60)), while the effect of starting a statin was non-significant in subjects with low albuminuria (HR 0.74 (0.44-1.24), P for interaction < 0.05). The effect of starting a statin was similar in subgroups with high and low hsCRP (P for interaction 0.34). When combining albuminuria and hsCRP subgroups, the start of statin treatment was associated with a lower risk of cardiovascular events dependent on albuminuria and not on the hsCRP level. CONCLUSIONS: The start of statin treatment is associated with a significantly lower absolute as well as relative risk of cardiovascular events in subjects with hypercholesterolemia and elevated albuminuria, whereas these drugs had less effect in subjects with normal albuminuria. PMID- 26358994 TI - The State of Bariatric Surgery in Canada. PMID- 26358995 TI - In conversation with Shelly Jamieson. PMID- 26358996 TI - Leadership Engagement and Workplace Violence Prevention: The Collaboration between a Large Community Hospital and its Unions. PMID- 26358997 TI - Pursuing Criminal Charges Against Patients who are Reported as Having Assaulted Healthcare Professionals: Considerations. AB - In two separate events in early 2014, a nurse was threatened with bodily harm by a patient in an inpatient psychiatry unit in Toronto. The nurses involved pursued criminal charges against the patients who made these threats. In response to questions regarding the procedure of criminally charging patients, and the supports available, a panel presentation was organized and presented for the inter-professional team. The key points from the panel are provided here as a resource for other organizations. This paper provides considerations learned from the Toronto Police Services, a Registered Nurse, a Nurse Manager, a Psychiatrist, a Bioethicist, a Legal representative and from Employee Relations. PMID- 26358998 TI - Managing Responsive Behaviours: A Wicked Problem Addressed through a Grassroots Approach. AB - Challenging responsive behaviours, such as aggression, wandering and social inappropriateness, exhibited by persons with neurological, mental health or developmental disorders are of increasing concern across Canada. These behaviours can cause distress or catastrophic outcomes for the person, others in care, caregivers and healthcare providers, and result in extensive resource utilization. The objective of this paper is to discuss the role and impact of a unique, grassroots provincial initiative aimed at networking among healthcare providers, decision-makers and caregivers across government ministries and service-provider agencies. This collaboration provides a model for informing service provision and policy development across multiple stakeholders. PMID- 26358999 TI - Olly Olly Oxen Free (or Ally Ally in Free): Playing Hide and Seek in Allocating Resources for Child and Youth Health. AB - There are powerful arguments for increased investment in child and youth health. But the extent to which these benefits can be realized is shaped by health institutions' priority setting processes. We asked, "What are the unique features of a pediatric care setting that should influence choice and implementation of a formal priority setting and resource allocation process?" Based on multiple sources of data, we created a "made-for-child-health" lens containing three foci reflective of the distinct features of pediatric care settings: the diversity of child and youth populations, the challenges in measuring outcomes and the complexity of patient and public engagement. PMID- 26359000 TI - Exploring Approaches to Successfully Achieving Comprehensive Order Set Adoption. AB - Healthcare providers are challenged to efficiently achieve evidence-based care for patients and their families. Clinical decision support tools are being introduced to facilitate knowledge transfer to care providers. Order sets are one of the tools. Using the realist review methodology and focus group of interview participants, this paper retrospectively explored relationships that lead to successful order set adoption. Findings demonstrate the need for regular review of clinical context. Technology can offer some enhancements but also introduces complex challenges. Ongoing software development is needed to improve delivery formats as well as incorporate effective tools for efficient continuous quality improvement. PMID- 26359001 TI - Extramural Pilot Project: Designated On-Call Intensivist in Tertiary Care Centre Improves Access to Critical Care Consultation/Referral and Resources. AB - Timely consultation with an intensivist will promote early and appropriate management of critically ill patients. We determined whether implementing a call roster of intensivists who did not have on-call responsibilities in an intensive care unit (ICU) and who received referrals from community physicians would improve access to critical care services. This program created efficiencies to critical care services by: timely access to consultation with an intensivist (<10 minutes) and/or subspecialist, timely referral to an appropriate institution (<30 minutes) and optimal resource utilization by determining the availability of ICU beds at non-tertiary care hospitals capable of providing the care needs of the patient, thus relieving pressure on the neighbouring tertiary/quaternary care centre. PMID- 26359002 TI - Resident Work Hour Restrictions and Change Management: A Cautionary Tale. AB - Residents are a significant part of coverage in many hospitals. Resident associations are negotiating work hour limits to prevent fatigue-induced medical errors. Our intensive care unit experienced an unexpected resident shortage and used the opportunity to trial a shift schedule for one month. Post-surveys were sent to nurses, attending physicians and residents to evaluate the effects on staff interactions, patient safety and education quality. The trial was clearly a failure on all fronts. Work hour restrictions are a reality in medical education, and administrators need to start considering alternative staffing models and discussing alternative schedules with their medicine faculty. PMID- 26359003 TI - Editorial overview: Host pathogens: New paradigms and tools to decipher and deconstruct the host-pathogen interaction. PMID- 26359005 TI - [Development and heritage: congratulations on the centennial birthday of Chinese Medical Association (CMA) & the 10(th) anniversary of Chinese Society of Critical Care Medicine]. PMID- 26359004 TI - HIV Prevalence Among Central American Migrants in Transit Through Mexico to the USA, 2009-2013. AB - HIV prevalence was estimated among migrants in transit through Mexico. Data were collected on 9108 Central American migrants during a cross-sectional study performed in seven migrant shelters from 2009 to 2013. Considerations focused on their sociodemographic characteristics, sexual and reproductive health, and experience with violence. Based on a sample of 46.6 % of respondents who agreed to be HIV tested, prevalence of the virus among migrants came to 0.71 %, reflecting the concentrated epidemic in their countries of origin. A descriptive analysis was performed according to gender: the distribution of the epidemic peaked at 3.45 % in the transvestite, transgender and transsexual (TTT) population, but fell to less than 1 % in men and women. This gender differential is characteristic of the epidemic in Central America. Furthermore, 23.5 % of TTTs and 5.8 % of women experienced sexual violence. The predominant impact of sexual violence on TTTs and women will influence the course of the AIDS epidemic. PMID- 26359006 TI - [The standardization of diagnosis and treatment of severe sepsis/septic shock and its practice]. PMID- 26359007 TI - [The value of changes in plasma B-type natriuretic peptide before and after spontaneous breathing trial in predicting weaning outcome in mechanically ventilated patients]. AB - OBJECTIVE: To evaluate the value of the change of B-type natriuretic peptide (BNP) in predicting weaning outcome of patients with mechanical ventilation in ICU. METHODS: We carried out a prospective cohort study on patients in ICU at Fuxing Hospital from July 2013 to January 2014. Patients expected to use mechanical ventilation for more than 24 hours were enrolled in our study. The plasma concentration of BNP was measured at the beginning of spontaneous breathing trial (SBT) and 2 hours after. According to the outcome of SBT, patients were divided into SBT failure group (group A), weaning failure group (group B) and weaning success group (group C). The levels of BNP before and after the SBT were compared among three groups. The receiver operating characteristic (ROC) curve analysis was used to evaluate the changes of BNP (DeltaBNP) and the rate of change (DeltaBNP%) in predicting weaning outcome. RESULTS: A total of 56 patients were enrolled in our study, 12 in group A, 11 in group B and 33 in group C. In group C, both DeltaBNP and DeltaBNP% [7.0, (-1.2, 45.5) ng/L; 6.1 (-2.1, 11.5)%] were significantly lower than those in group A [88.0 (58.0, 140.0) ng/L, P < 0.05; 20.5 (15.3, 40.3)%, P < 0.001] and group B [46.0 (17.5, 91.2) ng/L, P < 0.001; 24.3 (13.0, 32.5) %, P < 0.001]. The area under ROC curve (AUC) of DeltaBNP% to predict weaning success was 0.88 [95% CI 0.79-0.97; P < 0.001] and the cut-off value is 13.4% with relatively high sensitivity (84.8%) and specificity (82.6%). The AUC of DeltaBNP to predict weaning success was 0.80 [95%CI 0.69-0.92; P < 0.001] and the cut-off value is 80ng/L with high sensitivity 93.4% and mediocre specificity (47.9%). CONCLUSION: Either DeltaBNP% or DeltaBNP in the SBT can predict weaning outcome, in which DeltaBNP% seems better than DeltaBNP. PMID- 26359008 TI - [A pilot study of measuring inferior vena cava internal diameter on transverse section plane in different sites by ultrasonography]. AB - OBJECTIVE: To investigate the shape change index (SCI) of inferior vena cava (IVC) measured from subcostal area and right mid-axillary line through ultrasonography laying the foundation for future research about SCI and volume status. METHODS: A total of 107 patients were enrolled in the Critical Care Medicine Department of Peking Union Medical College Hospital from December, 2014 January, 2015. The maximal diameter (MXD) and the minimal diameter (MID) were measured transversely from subcostal area and right mid-axillary line. The SCI was calculated. RESULTS: Totally 47 patients (42 with spontaneous breathing and 5 on mechanical ventilation) achieved measurements on transversal plane from subcostal area and right mid-axillary line. (1) The internal diameter of IVC on longitudinal plane measured from subcostal area was statistically different from that measured from right mid-axillary line both at end inspiration (P=0.001) and at end expiration (P=0.027). (2) No difference were found in the SCI measured from subcostal and right mid-axillary line both at end inspiration and at expiration. (3) The internal diameter of IVC and the SCI measured on transversal plane from subcostal area correlated well with that measured from mid-axillary line both at end inspiration (SCI:r=0.866, P=0.000) and at end expiration (SCI: r=0.887, P=0.000). CONCLUSIONS: Inferior vena cava internal diameters and the shape change index measured through ultrasonography on transversal planefrom subcostal area are correlated well with those from mid-axillary line. Measurements from the two sites can be replacedby each other. PMID- 26359009 TI - [The efficacy and safety of daptomycin for the treatment of Gram-positive bacterial infections in Chinese population]. AB - OBJECTIVE: To investigate the efficacy and safety of daptomycin in Chinese patients with serious infections of Gram-positive coccus. METHODS: Clinical data were retrospectively collected from patients who were suspected with Gram positive coccal infections and received daptomycin treatment between August 2010 and October 2012. RESULTS: A total of 203 Chinese patients from 26 centers were enrolled in our study, including 94 microbiologically diagnosed. Staphylococcus aureus was the most common pathogen (33%, 31/94) with 45.2% (14/31) methicillin resistant Staphylococcus aureus (MRSA). According to the infection sites, primary bloodstream infection (45.8%, 93/203) was the most frequent, which was followed by skin and soft tissue infections (15.3%, 31/203). Seventy-seven cases (37.9%, 77/203) had bloodstream infections complicated with other infections (37.9%, 77/203), 13 of which were endocarditis. The clinical efficacy of intention-to treatment (ITT) and modified ITT (MITT) analysis were 70.44% (143/203) and 78.72% (74/94), respectively. Seven patients (3.4%) represented drug-related adverse effect, but no serious adverse effect was reported. Moderate creatine phosphate kinase (CPK) elevation was observed in 4 patients (2%), which returned to normal range after drug withdrawl. CONCLUSION: Daptomycin is effective and safe for Chinese patients with serious infections of Gram-positive cocci. (registration number NCT10212601). PMID- 26359010 TI - [The impact of admission renal dysfunction on in-hospital and long-term outcome of patients with ST-elevation myocardial infarction in Beijing]. AB - OBJECTIVE: To investigate impact of admission renal dysfunction on in-hospital and long-term outcome of patients with ST-elevation myocardial infarction (STEMI). METHODS: This was a multicentre, observational, prospective-cohort study. Totally 718 consecutive patients were admitted to 19 hospitals in Beijing within 24 hours of onset of STEMI. Estimation of glomerular filtration rate (eGFR) was calculated according to the abbreviated MDRD equation. The patients were categorized into two groups as renal preservation group (eGFR >= 60 ml . min 1 . 1.73 m-2) and renal dysfunction group (eGFR < 60 ml . min-1 . 1.73 m-2). The association between admission renal dysfunction and in-hospital and six-year outcome was evaluated. RESULTS: A total of 718 patients with STEMI were evaluated. There were 551 men and 167 women with age of (61.0 +/- 13.0) years. One hundred and thirty-three patients (18.5%) had renal dysfunction. Patients with renal dysfunction were more often female and older, more patients had hypertension, diabetes and heart failure, and more patients had >= Killip II classes on admission. These patients were less likely to present with chest pain. The in-hospital mortality (16.5% vs 2.6%, P < 0.001), major adverse cardiac events (MACE) (60.9% vs 24.4%, P < 0.001), six-year all-cause mortality (35.3% vs 11.4%, P < 0.001), six-year cardiac mortality (15.9% vs 5.7%, P = 0.001) and six year MACE (52.4% vs 28.0%, P < 0.001) were markedly increased in renal dysfunction group than in renal preservation group. After adjusting for other confounding factors, renal dysfunction was an independent predictor of in hospital MACE (OR 2.120, 95% CI 1.563-2.878, P = 0.003), six-year all-cause mortality (RR 2.122, 95%CI 1.127-3.996, P = 0.020) and six-year MACE (RR 1.586, 95% CI 1.003-2.530, P = 0.047). CONCLUSIONS: The mortality and MACE in STEMI patients with renal dysfunction were higher than in those with preserved renal function. Renal dysfunction evaluated by eGFR on admission is an important independent predictor of short-term and long-term outcome in patients with acute STEMI. PMID- 26359011 TI - [The clinical application of glycosylated hemoglobin A1c and glycated albumin values in cirrhosis patients with hyperglycemia]. AB - OBJECTIVE: To evaluate the diagnostic value of glycosylated hemoglobin A1c (HbA1c) and glycated albumin(GA) in hyperglycemia patients with liver cirrhosis (LCH). METHODS: One hundred LCH patients were divided into anemia and no-anemia group by Hb 110 g/L. The no-anemia group was further divided into low albumin (serum albumin <30 g/L), and high albumin group (serum albumin 30-<40 g/L). One hundred type 2 diabetes without liver cirrhosis were included as control group (T2DM). HbA1c, GA, fasting plasma glucose (FPG), postprandial 2h plasma glucose (2hPG) were collected for statistical analysis. RESULTS: (1) The HbA1c level in LCH with anemia tended lower than that in T2DM subjects [(6.76 +/- 2.20)% vs (7.34 +/- 1.23)%, P=0.06]; though the level of GA [(19.10 +/- 7.47)% vs (16.68 +/ 2.90)%, P<0.01] and 2hPG [(12.09 +/- 3.39) mmol/L vs (10.84 +/- 2.95) mmol/L, P<0.05] were significantly higher than that in T2DM group. (2) No-anemia subjects in LCH group with albumin <30 g/L had obviously higher GA levels than those with albumin 30-<40 g/L and T2DM (albumin >= 40 g/L) [(18.79 +/- 2.28)% vs (16.71 +/- 2.42)% and (16.73 +/- 2.96)%, P<0.01]; though the level of HbA1c of three groups above has no significant difference. (3) The level of HbA1c between LCH without anemia group and T2DM group had no significant difference (P>0.05); and the level of GA between LCH without anemia group with albumin 30-<40 g/L and T2DM group had no significant difference (P>0.05). (4) The HbA1c has a positive correlation with FPG and 2hPG in LCH (FPG:r=0.45, P<0.001; 2hPG:r=0.33, P=0.001) and T2DM subjects (FPG: r=0.76, P<0.001; 2hPG: r=0.81, P<0.001). GA also has a positive correlation with FPG and 2hPG in LCH (FPG: r=0.48, P<0.001; 2hPG: r=0.39, P<0.001) and T2DM subjects (FPG: r=0.74, P<0.001; 2hPG: r=0.76, P<0.001). CONCLUSION: It is unfavorable to use HbA1c to evaluate the blood glucose level in liver cirrhosis patients with Hb<110 g/L and to use GA in patients with serum albumin <30 g/L. PMID- 26359012 TI - [A preliminary study of the significance of autoantibodies against light chain of myeloperoxidase on pulmonary damages in myeloperoxidase-antineutrophil cytoplasmic antibody associated vasculitis]. AB - OBJECTIVE: To investigate the clinical characteristics of myeloperoxidase (MPO) antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (MPO-AAV) with pulmonary injury and the relationship between pulmonary injury and ANCA against light chain of MPO (LCMPO-ANCA). METHODS: A total of 195 patients with newly diagnosed primary active MPO-AAV were recruited in this prospective study. Indirect immunofluorescence assay was used to detect peri-nuclear ANCA (p-ANCA). Immunoblotting and ELISA were used to detect myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA). Clinical features of patients with both positive p-ANCA and MPO-ANCA were collected. Disease activity was evaluated by Birmingham Vasculitis Activity Score- version 3 (BVAS-V3) Recombinant light chain of MPO was used to coat substrate of LCMPO-ANCA by ELISA. The clinical characteristics of pulmonary injury and its correlation with serum levels of p-ANCA, MPO-ANCA and LCMPO-ANCA were explored. RESULTS: All 195 patients (64 male and 131 female), consisted of 191 patients (98.0%) with microscopic polyangiitis, 3 patients (1.5%) with granulomatosis with polyangiitis, and 1(0.5%) with eosinophilic granulomatosis with polyangiitis including 64 men and 131 women. Their mean age was (63.2 +/- 13.5) years old. The level of MPO-ANCA had a positive correlation with general BVAS-V3 (r=0.193, P=0.007) in all patients, and the level of LCMPO ANCA was positively related with the pulmonary BVAS-V3 (r=0.228, P=0.001). As for multiple systemic damages, the incidence of lung involvement was 60.51% (118/195), which ranked second to renal involvement (71.80%, 140/195). The most common pulmonary injuries represented as pulmonary infiltration of 80.51% (95/118), pleural effusion / pleurisy of 41.53% (49/118), pulmonary nodule or cavity of 22.03% (26/118). Compared with those without lung involvement, the patients with pulmonary injuries were older [(66.39 +/- 10.70) years old vs (58.30 +/- 15.72) years old; t=4.277, P=0.001], had a shorter course of disease [2.00(1.00,10.50) months vs 3.00(1.00,3.50) months; t=-2.283, P=0.024], and higher scores of general BVAS-V3 (18.21 +/- 6.08 vs 15.18 +/- 5.64; t=3.501, P=0.001). Also, in the patients with pulmonary lesions, the positive rate of LCMPO-ANCA was significantly higher (35.59% vs 6.49%; chi2 =21.569, P<0.001), and the level of LCMPO-ANCA was significantly higher (0.377 +/- 0.229 vs 0.285 +/- 0.079; t=3.399, P=0.001) than those without lung involvement. The pulmonary BVAS V3 in the patients with LCMPO-ANCA was significantly higher than that in the patients without LCMPO-ANCA (4.34 +/- 2.10 vs 2.59 +/- 2.52; t=4.301, P<0.001), whereas the pulmonary BVAS-V3 was not correlated with LCMPO-ANCA (r=0.035, P=0.708) in patients with lung injuries. CONCLUSION: Pulmonary injury was relatively common and insidious in patients with MPO-AAV. To monitor ANCA level is necessary in patients with pulmonary injury. LCMPO-ANCA might play an important role in the pathogenesis of pulmonary lesions in AAV. PMID- 26359013 TI - [An epidemiologic study of the relation between non-alcoholic fatty liver disease and glycosylated hemoglobin among middle-aged and aged people]. AB - OBJECTIVE: To study the correlation between non-alcoholic fatty liver disease (NAFLD) and glycosylated hemoglobin (HbA1c) in middle-aged and aged population. METHODS: A total of 4 127 in-service workers and retirees aged 45 years old or above from one petrochemical enterprise in Ningbo were enrolled in our study. The waistline, body mass index, blood pressure, fasting blood-glucose, blood lipid profile, glutamyltranspeptidase, HbA1c and epigastrium B ultrasound were investigated. According to the quartile of HbA1c level, participants were divided into four groups, namely, Q1 group <=5.2%, Q2 group >5.2%-5.4%, Q3>5.4%-5.6% and Q4 group>5.6%. The prevalence of NAFLD and clinical characteristics of each group were analyzed. Logistic regression was used to predict independent risk factors of NAFLD. RESULTS: The morbidity of NAFLD was 27.2% with 31.9% in male and 21% in female, which was significantly higher in men. In Q1, Q2, Q3 and Q4 group, the prevalence of NAFLD were 18.5% (178/961), 22.8% (185/812), 25.6% (280/1 095), 38.1% (480/1 259) respectively. With the increase of HbA1c level, the morbidity of NAFLD increased synchronously. The age, systolic pressure, total cholesterol, low density lipoprotein cholesterin and fasting blood-glucose were all elevated according to the increase of HbA1c in 1 123 NAFLD patients. Multi-factor logistic regression analysis indicated that high HbAlc level was the risk factor of NAFLD (OR=1.67, 95%CI 1.15-2.43, P=0.007). CONCLUSION: HbA1c is an independent risk factor of NAFLD and both of these are closely related to blood lipid metabolism disorder. PMID- 26359014 TI - [A clinical study of changes in retina and visual field in patients with early Parkinson's disease]. AB - OBJECTIVE: To characterize the changes of retinal structure and visual field mean defects (MD) in early Parkinson's disease (PD) and the related factors. METHODS: Twenty-five patients with early stage PD and 33 normal controls were enrolled in this study. PD patients were evaluated by unified Parkinson's disease rating scale (UPDRS) and Hoehn-Yahr (H-Y) stage in "off" period. All subjects undertook retina of retinal nerve fiber layer (RNFL) and macular examinations by optical coherence tomography (OCT), and MD by automatic visual field analyzer. RESULTS: (1) The average thicknesses of RNFL and C11 quadrant RNFL were thinner in PD group [(96.2 +/- 7.6)um and (124.4 +/- 18.4)um] than in healthy controls [(102.6 +/- 5.0)um and (135.4 +/- 21.8)um, respectively, P=0.000 and P=0.047]. Moreover, PD patients had a thinner average thickness of macular [(277.2 +/- 9.6) um vs (285.8 +/- 12.6) um, P=0.006], and smaller macular volume compared with controls [(10.0 +/- 0.3) mm3 vs (10.3 +/- 0.4) mm3, P=0.006]. However, there was no significant difference in MD between PD and control subjects [(0.43 +/- 2.75)dB vs (-0.18 +/- 1.41) dB, P=0.322]. (2) Pearson's correlation analysis showed that H-Y stage was negative correlated with the average RNFL thickness (r=-0.569), average macular thickness and volume (r=-0.501 and r=-0.417) in PD patients (all P<0.05). CONCLUSIONS: PD patients have thinner average thicknesses of RNFL, C11 quadrant RNFL and macular, smaller macular volume than those in normal controls. There were no significant differences in MD between two groups.There were negative relationships between H-Y stage, and retinal thickness and volume of PD patients. PMID- 26359015 TI - [A clinical study of functional dyspepsia and mental disorder co-morbidity]. AB - OBJECTIVE: To investigate the co-morbid state of mental disorder in patients with functional dyspepsia (FD) in a tertiary general hospital in China and explore the risk factors of the co-morbidity of FD and major depressive disorder (MDD). METHODS: This study was designed as a bilateral evaluation and structural psychiatric interview. Patients with FD and newly diagnosed outpatients with MDD in gastrointestinal and psychological departments were enrolled. FD was defined by Rome III criteria. The questionnaires including symptoms of FGIDs Roma III, the composite international diagnostic interview (CIDI 3.0) Chinese version, the Hamilton depression/anxiety rating scale (HAMD/HAMA), Montgomery-Asberg depression scale (MADRS) were involved in this study. All patients were administered by well trained physicians and investigators in face to face interview. RESULTS: A total of 69 patients have completed the valid questionnaires and interview, among whom 42 met FD criteria (FD group) and 27 with FD co-morbid MDD (co-morbid group). Male to female ratios were 17:25 and 10:17, the mean age (42.1 +/- 13.3) and (43.1 +/- 15.3) years respectively. The life-long co-morbidity of FD and MDD was 39.1% (27/69), while 31.9% (22/69) patients with FD were accompanied with other mental disorders rather than MDD. Patients in FD co-morbid MDD group had significantly more severe depression than those in FD group with HAMD-17 score 21.6+/-8.0 and 14.5 +/- 7.6, HAMA score 21.2 +/- 9.0 and 14.9 +/- 7.5 respectively (all P<0.01). Logistic regression analysis showed that high score of MADRS and complication with functional anorectal disorder may be the risk factors of FD co-morbid MDD [OR(95% CI) 1.12(1.06-1.19) and 7.07(1.12-44.53)]. CONCLUSIONS: The co-morbidity rate of FD with MDD in our hospital is high. In addition to MDD, other mental disorders also need to be paid attention in FD patients. FD co-morbid MDD patients suffered more severe depression and anxiety. The high score of MADRS and complication with functional anorectal disorder seem to be the risk factors of co-morbidity of FD and MDD. PMID- 26359016 TI - One-year post-discharge resource utilization and treatment patterns of patients with acute coronary syndrome managed with percutaneous coronary intervention and treated with ticagrelor or prasugrel. AB - OBJECTIVE: Our objective was to compare 1-year real-world healthcare resource utilization (HRU), associated charges, and antiplatelet treatment patterns among patients with acute coronary syndrome (ACS) managed with percutaneous coronary intervention (PCI) and treated with ticagrelor or prasugrel. METHODS: Using the ProMetis-Lx database, adult ACS-PCI patients treated with ticagrelor or prasugrel post-discharge were identified between 1 August 2011 and 31 May 2013 and propensity matched to adjust for baseline differences. RESULTS: Before matching, ticagrelor-treated patients (n = 2991) were older with increased baseline ischemic and bleeding risks compared with prasugrel-treated patients (n = 12,797). After matching, ticagrelor patients had higher all-cause HRU (2.5 vs. 2.4 per patient per month; P = 0.012) and cardiovascular (CV) HRU (0.4 vs. 0.3 per patient per month; P = 0.026), with the difference in CV rehospitalizations (17.7 vs. 15.7 %; P = 0.011) primarily driven by congestive heart failure (CHF) (4.9 vs. 3.8 %; P = 0.02). All-cause charges within 1 year did not significantly differ between groups ($US5456 vs. 4844 per patient per month; P = 0.37), but dyspnea-related total charges were significantly higher with ticagrelor ($US139 vs. 95 per patient per month; P = 0.005). Although infrequent, switching was slightly higher with ticagrelor (8.3 vs. 6.0 %; P < 0.001) at 1 year, and mean persistence was slightly longer with prasugrel (150 vs. 159 days; P = 0.002), with no significant difference in mean adherence (61 vs. 63 %; P = 0.17). CONCLUSION: Overall monthly HRU was slightly lower with prasugrel than with ticagrelor, with no significant difference in bleeding HRU. Prasugrel was associated with slightly higher pharmacy charges, but lower dyspnea charges, resulting in no significant difference in total charges. Patients receiving prasugrel tended to use it for longer than those receiving ticagrelor as less switching occurred. These findings may aid decision making, but must be tempered due to inherent study limitations. PMID- 26359017 TI - Accuracy in obtaining 100 MUg from 10 mg of morphine for spinal anesthesia. AB - STUDY OBJECTIVE: Dilution is often required to obtain appropriate concentrations of intrathecal morphine for analgesia. We compared techniques of diluting by measuring the quantity of morphine actually obtained in the final solution. DESIGN: This is an experimental study by 3 experienced anesthesiologists. SETTING: The setting is at a university teaching hospital. PATIENTS: There are no patients. INTERVENTIONS: There are no interventions. MEASUREMENTS: Five techniques for obtaining 100 MUg from 10 mg/mL were compared: technique 1 (T1) = extraction up to 0.1 graduation on a 1-mL syringe, followed by simple dilution (SD). Technique 2 (T2) = As for T1 but syringe was shaken to mix solution. Technique 3 (T3): SD with 10-mL syringe. Technique 4 (T4): Double dilution with 10-mL syringe. Technique 5 (T5): Extraction up to the 0.1 graduation of a 1-mL syringe, then SD, then shake solution by hand. Three tests using high-performance liquid chromatography with ultraviolet were performed on each syringe prepared 3 consecutive times, namely, at the first (beginning, B), fifth (middle, M) and last (end, E) milliliter or 0.1 mL (depending on syringe type). MAIN RESULTS: Average overall concentrations were 208 +/-19, 199 +/-24, 120 +/-13, 136 +/-9, and 119 +/-16 MUg/0.1 mL, T1-T5, respectively. By Kruskal-Wallis test, we classified the techniques according to the magnitude of the difference between the observed concentration of morphine and the desired (theoretical) concentration of 100 MUg/0.1 mL. In ascending order, techniques ranked as follows: T5 (smallest difference), T3, T4, T2, and T1 (greatest difference) (P = .0001). CONCLUSIONS: There is significant variability in the concentration of morphine actually contained in final solutions after dilution. Morphine presented in different premixed concentrations increases the risk of error. We advocate technique 5 as described above, whereas technique 1 should be prohibited. PMID- 26359019 TI - Clinical outcomes of lingual orthodontic treatment: a systematic review. AB - OBJECTIVES: To assess the available evidence on the effectiveness of lingual orthodontic treatment and related clinical parameters through a systematic review of relevant studies. MATERIALS AND METHODS: Eligible clinical studies published from January 2000 to March 2015 were identified through electronic (five major databases) and hand searches. Risk of bias was assessed using the Cochrane risk of bias tool for prospective studies and a specially designed tool for retrospective studies. RESULTS: From the 3734 articles identified by the search, after application of specific inclusion and exclusion criteria, 16 papers were included in the study. Eleven studies were retrospective, four were prospective, and only one was a RCT. In detail, six studies evaluated differences of the treatment outcome from the pre-treatment set-up prediction, two studies evaluated the effect of treatment on periodontal and microbial parameters, and 10 studies assessed various clinical treatment related parameters. Despite several promising findings, the quality of evidence supporting them was found to be low in most cases. CONCLUSIONS: This systematic review showed encouraging results on the clinical outcome of lingual orthodontic treatment, especially in regards to the achievement of individualized treatment goals and the reduction of decalcifications on the bonded surfaces of the teeth. However, additional well designed prospective clinical trials with larger samples are needed to confirm those findings. Several aspects of lingual orthodontic treatment were difficult to be conclusively evaluated due to the study design, the heterogeneity, the small samples sizes, and the high risk of bias seen in the majority of the included studies. PMID- 26359020 TI - [Physicians should manage the chronic constipation reasonably]. PMID- 26359018 TI - Combining the ASA Physical Classification System and Continuous Intraoperative Surgical Apgar Score Measurement in Predicting Postoperative Risk. AB - The surgical Apgar score predicts major 30-day postoperative complications using data assessed at the end of surgery. We hypothesized that evaluating the surgical Apgar score continuously during surgery may identify patients at high risk for postoperative complications. We retrospectively identified general, vascular, and general oncology patients at Vanderbilt University Medical Center. Logistic regression methods were used to construct a series of predictive models in order to continuously estimate the risk of major postoperative complications, and to alert care providers during surgery should the risk exceed a given threshold. Area under the receiver operating characteristic curve (AUROC) was used to evaluate the discriminative ability of a model utilizing a continuously measured surgical Apgar score relative to models that use only preoperative clinical factors or continuously monitored individual constituents of the surgical Apgar score (i.e. heart rate, blood pressure, and blood loss). AUROC estimates were validated internally using a bootstrap method. 4,728 patients were included. Combining the ASA PS classification with continuously measured surgical Apgar score demonstrated improved discriminative ability (AUROC 0.80) in the pooled cohort compared to ASA (0.73) and the surgical Apgar score alone (0.74). To optimize the tradeoff between inadequate and excessive alerting with future real time notifications, we recommend a threshold probability of 0.24. Continuous assessment of the surgical Apgar score is predictive for major postoperative complications. In the future, real-time notifications might allow for detection and mitigation of changes in a patient's accumulating risk of complications during a surgical procedure. PMID- 26359021 TI - [The impact of stress and coping strategies on health-related quality of life in ulcerative colitis]. AB - OBJECTIVE: To further understand factors that influence health-related quality of life (HRQOL) in patients with ulcerative colitis (UC), especially the role of perceived stress and coping modes in Chinese patients with UC. METHODS: This study was a cross-sectional study. Patients with UC were recruited from July 2013 to September 2014 in Peking Union Medical College Hospital. HRQOL was measured using the inflammatory bowel disease questionnaire (IBDQ). Perceived stress was measured by Perceived Stress Scale (PSS). Coping strategy was evaluated using Medical Coping Modes Questionnaire (MCMQ). Demographic data, course of the disease, clinical disease activity, and disease phenotype according to Montreal classification were also collected. Univariate analyses were conducted to determine which variables were associated with HRQOL, and those were statistically significant were entered into a multivariate regression model. RESULTS: We recruited 214 patients (response rate 92.2%), whose median age was 37.5 (29.0, 49.3) years old and median course of UC was 4 (2, 9) years. Through univariate analyses, better HRQOL was significantly associated with regular medical visits, lower number of previous relapses and hospitalizations, no steroid use, Montreal E1, lower Mayo scores, clinical remission, less perceived stress and less acceptance strategy use. However, multivariate analyses revealed that perceived stress (OR=1.112, 95% CI 1.058-1.169), acceptance (OR=0.310, 95% CI 0.141-0.685), number of hospitalizations (OR=2.924, 95% CI 1.328-6.437) and clinical activity (OR=5.058, 95% CI 2.312-11.066) were most strongly related to HRQOL. CONCLUSIONS: HRQOL of UC patients are not only associated with clinical activity of the disease, but also associated with coping strategy and perceived stress. Further research needs to focus on whether or not relieving stress and guiding patients to cope with ulcerative colitis would improve HRQOL. PMID- 26359022 TI - [An analysis of vitamin D receptor gene polymorphisms and serum 25-hydroxyvitamin D levels in patients with Crohn's disease]. AB - OBJECTIVE: To investigate the association of Crohn's disease (CD) with vitamin D receptor (VDR) gene polymorphisms and serum 25-hydroxyvitamin D [25(OH)D] level. METHODS: A total of 297 CD patients and 446 healthy controls were enrolled in our study. Four single nucleosides of VDR (Fok I, Bsm I, Apa I and Taq I) were genotyped by SNaPshot. Serum 25(OH)D levels were tested by electro chemiluminescence immunoassay in 124 CD patients and 188 matched random controls. RESULTS: By Chi-square test and Bonferroni correction, the frequencies of mutant allele (A) and mutant genotype (GA+AA) of Bsm I were significantly decreased in CD patients compared to controls [3.70% (22/594) vs 7.51% (67/892), 95% CI 0.289 0.776, P=0.002; 7.41%(22/297) vs 14.80% (66/446), 95% CI 0.277-0.765, P=0.002, respectively]. The similar results were seen for the mutant allele (C) and mutant genotype (TC+CC) of Taq I [4.21% (25/594) vs 7.62% (68/892), 95% CI 0.333-0.852, P=0.008; 8.42% (25/297) vs 14.57% (65/446), 95% CI 0.331-0.877, P=0.012]. The analyses of linkage disequilibrium (LD) and haplotype were performed by Haploview 4.2 and R software, respectively. The Bsm I, Apa I and Taq I polymorphic loci were found to be in a strong LD, and the AAC haplotype was significantly reduced in CD patients compared to controls [3.14% vs 6.46%, 95% CI 0.273-0.815, P=0.004]. The further serological analysis showed that average serum 25(OH)D level in CD patients was significantly lower than that of controls [(15.46+/ 8.11) ug/L vs (21.64+/-9.45) ug/L, P<0.001]. By linear regression analysis, serum 25(OH)D levels in CD patients were negatively correlated to Crohn's disease activity index (beta=-0.829, P<0.001), platelet count (beta=-0.253, P<0.001) and the ratio of neutrophils (beta=-0.136, P=0.005) independently, whereas positively related to erythrocyte sedimentation rate (beta=0.191, P=0.001). Furthermore, logistic regression analysis was applied for establishing the models of gene environment interaction. In result, both the mutant genotype (CA+AA) of Apa I and vitamin D deficiency (<20 ug/L) were shown to be the independent risk factors for CD (OR=7.580, 95% CI 2.983-19.261, P<0.001; OR=2.842, 95% CI 1.300-6.211, P=0.009, respectively). Besides, vitamin D deficiency in CD patients had multiplicative interactions with the mutant genotype (TC+CC) of Fok I, genotype (CA+AA) of Apa I and genotype (TC+CC) of Taq I, respectively (OR=0.419, 95% CI 0.194-0.906, P=0.027; OR=0.309, 95% CI 0.111-0.855, P=0.024; OR=5.841, 95% CI 1.082-31.538, P=0.040; respectively). CONCLUSIONS: VDR (Bsm I, Apa I and Taq I) polymorphisms and serum 25(OH)D levels are significantly related to CD. Both the mutant genotype (CA+AA) of Apa I and vitamin D deficiency are independent risk factors of CD. The mutations of VDR (Fok I, Apa I and Taq I) and vitamin D deficiency might have a synergistic effect on CD susceptibility. PMID- 26359023 TI - [The distribution of frequent premature ventricular contractions originated from left/right ventricular and characteristics of radiofrequency ablation]. AB - OBJECTIVE: The aim of this study was to investigate the differences on origin distribution and radiofrequency ablation characteristics between premature ventricular contractions (PVC) from left and right ventricular. METHODS: A total of 354 frequent PVC patients were enrolled. Two hundred and eighty patients were PVCs with right ventricular origin (group RV) and 74 patients with left ventricular origin (group LV). The age, gender, ablation power, temperature and duration, time of target potential before QRS onset, fluoroscopic time, procedure time and success rate were compared between the two groups. RESULTS: Majority PVCs (79.10%) were of right ventricular origin, in which the most common site was at right ventricular outflow tract (RVOT) (55.93%); whereas, only 20.90% were of left ventricular. There were significantly differences between group RV and group LV in age [(44.7+/-13.6) yrs vs (49.6+/-15.9) yrs, P=0.017], gender [male: 35.4%(99) vs 55.4%(41), P=0.002], time of target potential before QRS onset [(37.9+/-16.2) ms vs (31.3+/-11.7) ms, P=0.008], procedure time [(85.1+/-36.9) min vs (100.8+/-45.5) min, P=0.017], fluoroscopic time [(12.3+/-9.2) min vs (15.9+/-10.8) min, P=0.028] and success rate (96.4% vs 89.2%, P=0.012). CONCLUSIONS: Radiofrequency ablation of PVCs was a safe and effective method. Subjects with RV PVCs are younger and more females than subjects with LV PVCs. The radiofrequency ablation for RV PVCs was easier, and the success rate was higher than that for LV PVCs. PMID- 26359024 TI - [Effectiveness and safety of initiation of once-daily insulin detemir in Chinese patients with type 2 diabetes previously treated with different quantities of oral anti-diabetic drugs: subgroup analysis of the Chinese SOLVETM Study]. AB - OBJECTIVE: To evaluate the effectiveness and safety on once-daily (OD) insulin detemir (IDet) in Chinese patients with type 2 diabetes mellitus (T2DM) who were treated with different types or combinations of oral anti-diabetic drugs (OADs). METHODS: The SOLVETM study was a 24-week observational study on the initiation of IDet OD in T2DM patients with uncontrolled hyperglycemia on diet, exercise, and one or more OADs. Subjects were grouped based on the numbers of OADs taken before (>2-OAD, 2-OAD, and 1-OAD groups). Efficacy and safety endpoints were evaluated and compared in different groups. RESULTS: This study includes 3 272 patients, among them 464 (14.2%) were treated with more than 2 OADs, 1511 (46.2%) with 2 OADs, and 1 218 (37.2%) with 1 OAD before the study. The mean glycosylated hemoglobin A1c (HbA1c) was 8.4%, 8.3%, 8.4% at baseline, and 7.3%, 7.2%, 7.1% at the end of 24-week in each 3 groups (all P<0.001 vs. baseline values). The HbA1c reductions were not statistically significant different among groups. Body weight tended to decrease in patients from all groups, however, only that in the 2-OAD group reached statistically significance. No major hypoglycaemia events were reported. However, the overall minor hypoglycaemia rate in the 2-OAD group was higher at the end of the study than that at baseline (P<0.05). No differences in the rate of nocturnal minor hypoglycaemia were observed in all groups after IDet treatment. CONCLUSION: Initiation of IDet OD was effective and well-tolerated in Chinese patients with T2DM whose glycemia was poorly controlled on OADs irrespective of the number of OADs taken before. (registration number NCT00825643). PMID- 26359025 TI - [The changes in renin-angiotensin-aldosterone-system in different subtypes of Cushing's syndrome]. AB - OBJECTIVE: Cushing's syndrome is a clinical condition resulting from chronic exposure to excess glucocorticoid. As a consequence, long-term hypercortisolism contributes significantly to the development of systemic disorders by direct and/or indirect effects. The present study was to analyze the changes of renin angiotensin-aldosterone-system in different subtypes of Cushing's syndrome on the standard posture test. METHODS: We retrospectively reviewed 150 patients with histologically confirmed Cushing's syndrome treated at the PLA General Hospital between 2002 and 2014. Among them, 128 patients were diagnosed as adreno-cortico tropic-hormone (ACTH)-independent Cushing's syndrome, and 22 were ACTH-dependent Cushing's syndrome. All patients were undertaken the posture test. Plasma renin activity (PRA), angiotensin II, plasma aldosterone concertration (PAC) levels were measured before and after the test. RESULTS: Basal plasma PRA [0.5 (0.2,1.3)ug.L(-1).h(-1), angiotensin II [(48.9+/-20.1) ng/L] and PAC [(285.0+/ 128.1) pmol/L] levels were within the normal range in supine position. Compared with the subjects with ACTH-independent Cushing's syndrome, the basal PAC levels were higher in subjects with ACTH-dependent Cushing's syndrome [(348.0+/-130.4) pmol/L vs (274.2+/-125.0) pmol/L, P<0.05]. However, the PAC response in subjects with ACTH-dependent Cushing's syndrome [(49.7+/-26.4)%] was significantly lower than that in those with ACTH-independent Cushing's syndrome [(81.2+/-69.3)%] upon upright posture stimulation (P<0.05). There were no statistical significances in PRA and angiotensin II levels between the two groups. The basal PAC and PRA levels were positively correlated with ACTH, whereas PAC response was negatively correlated with ACTH. CONCLUSIONS: The renin-angiotensin-aldosterone-system activity in subjects with Cushing's syndrome was similar to that in normal control. The basal PAC level and its response to upright posture are differently associated with ACTH level in Cushing's syndrome. PMID- 26359026 TI - [The clinical presentation and gene mutation of probands in Chinese patients with Charcot-Marie-Tooth disease]. AB - OBJECTIVE: To identify the gene mutation of Chinese Charcot-Marie-Tooth (CMT) pedigrees and investigate the association of gene mutation to the clinical manifestations and electrophysiology, and the underlying mechanisms. METHODS: A total of 105 pedigrees with CMT in our hospital were enrolled from January, 2007 to December 2013. The clinical features, CMT neuropathy score (CMTNS) and electrophysiological data were collected. Gene mutations were analyzed using multiplex ligation-dependent probe amplification (MLPA) and Sanger gene sequencing. RESULTS: We found 31(29.5%) PMP22 duplication pedigrees, 8(7.6%) GJB1 mutation pedigrees, 4(3.8%) MFN2 mutation pedigrees, 4(3.8%) HSPB1 mutation pedigrees, 3(2.9%) MPZ mutation pedigrees and 1(1.0%) PMP22 mutation pedigree. In Chinese Han population, the proportion of PMP22 duplication was relatively lower than that in western countries and manifested with classical clinical characteristics of CMT. Subjects with axonal CMT often presented with isolated lower extremity injury and with central nervous system involvement. Hereditary motor neuropathy might be underestimated in clinical setting and should be differentiated from motor neuron disease. CONCLUSIONS: The gene frequency distribution in patients with CMT in Chinese Han population is different from that in patients from western countries. We should establish our own epidemiological data of CMT in Chinese Han population. PMID- 26359027 TI - [The distinctive characteristics of ultrasonic imaging of enthesitis in spondyloarthritis patients]. AB - OBJECTIVE: To explore the distinctive ultrasonographic characters of enthesitis in patients with spondyloarthritis (SpA) and evaluate the diagnostic value of ultrasonography in SpA by comparing ultrasonography of enthesis in the lower limbs of patients with SpA, rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: Entheses in the lower limbs (quadriceps tendon, proximal patellar ligament, distal patellar ligament, achilles tendon and plantar aponeurosis) were detected in SpA, RA, OA patients and health controls by ultrasonographic examination. RESULTS: A total of 46 SpA, 23 RA and 12 OA patients were enrolled in this study, with 26 SpA and 7 RA patients complaining of heel pain (P<0.05). There were 126 enthesal sites (126/460, 27.2%) were detected abnormal in SpA group, compared with 54 of 230 (23.5%) sites in RA group and 27 of 120 (22.5%) sites in OA group (P>0.05). Sixty five (70.7%) sites of the distal patellar ligaments were abnormal in SpA group, while that were 19 (41.3%) in RA group (P<0.05) and 13 (54.2%) in OA group. Twenty six sites of tendon thickness and 22 sites of bone erosion in the distal patellar ligaments were found in SpA group, while only one site of each in RA group (P<0.05) and 4 sites of tendon thickness in OA group (P<0.05) were found.Tendon thickness, bursal synovitis and bone erosion coexisting in one distal patellar ligament indicated SpA, the sensitivity, specificity and the area under the curve (AUC) of which were 70.7%, 65.5% and 0.740, respectively. CONCLUSION: Tendon thickness and bone erosion of entheses were more likely the distinctive ultrasonographic characters of enthesitis in SpA patients. Tendon thickness, bursal synovitis and bone erosion in the distal patellar ligament could be an ideal tool for SpA diagnosis. PMID- 26359028 TI - [The effects of continuous positive airway pressure ventilation on hypersensitive C reaction protein and 8-isoprostane in patients with obstructive sleep apnea hypopnea syndrome]. AB - OBJECTIVE: To observe the effect of continuous positive airway pressure ventilation on hypersensitive C reaction protein (hsCRP) and 8-isoprostane in patients with obstructive sleep apnea hypopnea syndrome (OSAHS). METHODS: A total of 78 OSAHS patients were enrolled and monitored by polysomnography (PSG) in January to March, 2013. Another 40 healthy persons were chosen as controls during the same time. According to apnea hypopnea index (AHI) and oxygen saturation, the patients were divided into mild, moderate and severe groups. Blood and urinary 8 isoprostane and hsCRP levels were detected before and after monitoring. After continuous positive airway pressure treatment for three months, blood and urinary 8-isoprostane and hsCRP were also detected in three groups. RESULTS: (1) In OSAHS patients, blood 8-isoprostane levels before and after sleep monitoring were (273.80+/-55.83) ng/L and (337.18+/-56.28) ng/L urinary 8-isoprostane (35.65+/ 7.08) ng/L and (48.30+/-14.17) ng/L, hsCRP (7.63+/-6.10) ug/L and (9.68+/ 8.55)ug/L, respectively. Each parameter reached a significant difference before and after sleep (P<0.05). (2) The levels of blood CRP and urinary 8-isoprostane in the control group before sleep were (4.56+/-2.43) ug/L, (264.14+/-33.61) ng/L, (32.77+/-9.61) ng/L, after sleep were (4.33+/-2.08) ug/L, (284.27+/-47.51) ng/L, (31.13+/-8.24) ng/L. All the levels were less than those of OSAHS group (P<0.05). (3) The levels of blood 8-isoprostane in mild, moderate and severe groups after monitoring were (308.16+/-53.48) ng/L, (327.36+/-59.05) ng/L, (340.39+/-55.31) ng/L respectively, and urinary 8-isoprostane were (35.23+/-11.28) ng/L, (38.30+/ 10.89) ng/L, (44.57+/-12.69) ng/L, hsCRP were (5.63+/-4.26) ug/L, (6.96+/-4.43) ug/L, (8.92+/-7.84) ug/L. None of these three parameters showed significant difference between the three groups (P>0.05). However, compared with the control group, blood and urine 8-isoprostane and hsCRP levels of any groups had significant differences (all P values<0.05). (3) There was no significant difference in the levels of hsCRP and 8-isoprostane after sleep between the three groups in OSAHS (P>0.05). (4) Urinary 8-isoprostane level after PSG was positively correlated with hsCRP (r=0.498, P<0.01). Either 8-isoprostane or hsCRP level was correlated with AHI (r=0.479, r=0.550; P<0.01). 8-isoprostane and hsCRP levels were positively correlated with time of blood hemoglobin oxygen saturation below 90% (r=0.413, r=0.502; P<0.01). (5) After continuous positive airway pressure treatment, the levels of 8-isoprostane and hsCRP both in blood or urine were decreased in the three groups of OSAHS patients (P<0.05). CONCLUSIONS: Long term intermittent hypoxia in patients with OSAHS results in enhanced oxidative stress reaction and over-generated inflammatory mediators. There is a positive correlation between oxidative stress and inflammatory mediators, which promotes each other, leading to the organ dysfunction induced by hypoxia. PMID- 26359029 TI - Maternal gestational betaine supplementation-mediated suppression of hepatic cyclin D2 and presenilin1 gene in newborn piglets is associated with epigenetic regulation of the STAT3-dependent pathway. AB - Betaine, which donates methyl groups through methionine metabolism for DNA and protein methylation, is critical for epigenetic gene regulation, especially during fetal development. Here we fed gestational sows with control or betaine supplemented diets (3 g/kg) throughout the pregnancy to explore the effects of maternal betaine on hepatic cell proliferation in neonatal piglets. Neonatal piglets born to betaine-supplemented sows demonstrated a reduction of cell number and DNA content in the liver, which was associated with significantly down regulated hepatic expression of cell cycle regulatory genes, cyclin D2 (CCND2) and presenilin1 (PSEN1). Moreover, STAT3 binding to the promoter of CCND2 and PSEN1 was also lower in betaine-exposed piglets, accompanied by strong reduction of STAT3 mRNA and protein expression, along with its phosphorylation at Tyr705 and Ser727 residues. Also, prenatal betaine exposure significantly attenuated upstream kinases of STAT3 signaling pathway (phospho-ERK1/2, phospho-SRC and phospho-JAK2) in the livers of neonates. Furthermore, the repressed STAT3 expression in the liver of betaine-exposed piglets was associated with DNA hypermethylation and more enriched repression histone mark H3K27me3 on its promoter, together with significantly up-regulated expression of H3K27me3 and enhancer of zeste homolog 2 (EZH2) proteins, as well as miR-124a, which targets STAT3. Taken together, our results suggest that maternal dietary betaine supplementation during gestation inhibits hepatic cell proliferation in neonatal piglets, at least partly, through epigenetic regulation of hepatic CCND2 and PSEN1 genes via a STAT3-dependent pathway. These neonatal changes in cell cycle and proliferation regulation may lead to lower liver weight and hepatic DNA content at weaning. PMID- 26359030 TI - Sirt1 mediates the effects of a short-term high-fat diet on the heart. AB - High-fat diet leads to development of cardiac dysfunction through molecular mechanisms poorly known. The aim of this study is to elucidate the early events in cardiac dysfunction caused by a high-fat diet, before massive alterations due to obesity and indirect mechanisms of heart damage take place. Moreover, we analyzed the role of Sirt1, a major mediator of cardiac gene regulation, in these effects. Short-term high-fat feeding (5 weeks) caused a similar mild increase in body weight and triglyceridaemia in wild-type (wt) and Sirt1(+/-) mice. The high fat diet suppressed the expression of lipid catabolism (PPARalpha target) gene expression in the hearts of wt mice, but not Sirt1(+/-) mice. Pro-inflammatory genes were induced and estrogen-related receptor-alpha (ERRalpha) target genes was suppressed in the hearts of wt fed the high-fat diet, but not in Sirt1(+/-) mice. We found the formation of a complex between PPARalpha and Sirt1 in wt mice under high-fat diet conditions which might account for suppression of the ERRalpha pathway. Sirt1 haploinsufficiency impairs the formation of this complex and promotes the binding of PPARalpha to the p65 subunit of NF-kappaB, thereby mediating inhibition of pro-inflammatory pathways and induction of PPARalpha target genes. Short-term high-fat diet causes metabolic and inflammatory alterations in heart, and Sirt1 is critical for mediating these cardiac alterations. The capacity of Sirt1 to interact with transcriptional regulators such as NF-kappaB and PPARalpha appears to be involved in the cardiac responsiveness to a high-fat diet. PMID- 26359032 TI - [When endodontics encounters implant]. PMID- 26359031 TI - Association of Meloxicam Use with the Risk of Acute Pancreatitis: A Case-Control Study. AB - BACKGROUND AND OBJECTIVE: No sufficient research has focused on the relationship between meloxicam use and acute pancreatitis. This study aimed to explore this issue in Taiwan. METHODS: This case-control study was conducted using the database of the Taiwan National Health Insurance Program. In all, there were 6780 cases aged 20-84 years who were newly diagnosed with acute pancreatitis during the period 1998-2011, and 21,393 control subjects without acute pancreatitis. Cases and controls were matched for sex, age and comorbidities. Odds ratios (ORs) and 95% confidence intervals (CIs) were measured to explore the associations between acute pancreatitis, meloxicam use and comorbidities, using a multivariable unconditional logistic regression model. RESULTS: After controlling for potential confounding factors, the adjusted OR for acute pancreatitis was 1.76 (95% CI 1.30-2.40) for subjects with current use of meloxicam, in comparison with subjects who had never used meloxicam. The adjusted OR decreased to 1.29 (95% CI 0.82-2.03) for subjects with late use of meloxicam, but without statistical significance. CONCLUSIONS: Current use of meloxicam is associated with increased odds of acute pancreatitis. Clinicians should consider the potential risk of acute pancreatitis when prescribing meloxicam. PMID- 26359033 TI - [Diagnosis and treatment strategy of persistent endodontic diseases]. PMID- 26359034 TI - [Clinical opplication of novel type flowable resin in odontal restoration]. PMID- 26359035 TI - [The current status and prospect of materials for vital pulp therapy]. PMID- 26359036 TI - [Gene regulatory system for competence development in Streptococcus mutans]. PMID- 26359037 TI - [Effect of lipopolysaccharide on the stromal cell-derived factor-1 expression in human stem cells from apical papilla]. AB - OBJECTIVE: To investigate the expression of stromal cell-derived factor-1 (SDF-1) in human stem cells from apical papilla (SCAP), and to evaluate the effect of lipopolysaccharide (LPS) on SDF-1 expression by SCAP. METHODS: SCAP were isolated from dental papilla of human immature third molars. The expression of SDF-1 was evaluated by reverse transcription-PCR (RT-PCR). After SCAP being exposed to different concentrations (0.1, 1.0, 10 mg/L) of LPS for 24 and 48 h, the effect of LPS on cell proliferation and gene expression of SDF-1 was investigated by cell counting kit-8 and real-time PCR respectively, while cells without LPS stimulation were considered as negative control. RESULTS: LPS had no significant effect on SCAP proliferation until day 7. RT-PCR assays demonstrated that SCAP expressed SDF-1 mRNA. Different concentrations of LPS significantly promoted the SDF-1 expression in SCAP after 24 h (F = 12.102, P = 0.002) and 48 h (F = 39.054, P < 0.001) exposure, with relative gene expression ratio (experimental/control) increased to 1.4 +/- 0.1, 2.2 +/- 0.4, 2.3 +/- 0.5 in 24 h group and 2.1 +/- 0.4, 3.4 +/- 0.3, 3.8 +/- 0.5 in 48 h group. CONCLUSIONS: Isolated SCAP in cultures have the expression of SDF-1 mRNA. LPS can significantly promote the expression of SDF-1 in SCAP. PMID- 26359038 TI - [Computational fluid dynamics analysis of the flow of four irrigations in root canal]. AB - OBJECTIVE: To analyze the flow of four irrigations in a root canal with different needle-insertion depth by using a computational fluid dynamics (CFD) model in order to provide a reference to the needle placement in clinical practice. METHODS: The density and viscosity of 5.25% sodium hypochlorite (A), 3% sodium hypochlorite (B), 17% ethylenediaminetetraacetic acid (EDTA, C), 2% chlorhexidine (D) were measured. A CFD model by ICEM software was used to simulate irrigant flow from an open-ended flat needle positioned at the depth of 1, 3, 5 mm to the physiological apical within the root canal. Velocity, wall shear stress and pressure in the root canal were evaluated after setting the computing conditions with FLUENT14.0 software. RESULTS: All the wall shear stress generated by four fluids was at peak when the needle was positioned 1 mm to the physiological apical, which were 6.72 * 103 Pa(A), 6.35 * 103 Pa(B), 7.47 * 103 Pa(C), 5.26 * 103 Pa(D), respectively. With the distance increasing, wall shear stress gradually decreased. The wall shear stress of A, B, C, D was 2.31 * 103, 2.05 * 103, 2.59 * 103 and 1.81 * 103 Pa, respectively in 3 mm group. The wall shear stress of A, B, C, D was 2.16 * 103, 1.91 * 103, 2.42 * 103, 1.71 * 103 Pa, respectively in 5 mm group. CONCLUSIONS: It was recommended that the distance between the needle and physiological apical is 1-3 mm when flushing the root canal. The injection speed of 17% EDTA should be slower than that of the other three solutions. PMID- 26359039 TI - [Summary of The 9th National Academic Conference of Cariology and Endodontology]. PMID- 26359040 TI - [The inhibitory effect of metformin on oral squamous cell carcinoma]. AB - OBJECTIVE: To investigate the effect of metformin on the proliferation and cell apoptosis of oral squamous cell carcinoma (OSCC) (HSC-3, HSC-4) in vitro and in vivo. METHODS: HSC-3, HSC-4 cells were treated with metformin at different concentration (2-50 mmol/L) for 24, 48 or 72 hours. In vitro cell proliferation ability was determined by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and colony formation assay. Cell cycle progression was assessed by flow cytometry. Cell apoptosis was tested by both TdT-mediated dUTP nick-end labeling (TUNEL) assay and flow cytometry. The activation of related cell markers was examined by immunohistochemistry. Xenograft mouse model was used to demonstrate the in vivo anti-tumor effect of metformin. A total of 30 BALB/c mice were randomly divided into control groups (water + phosphate buffer saline, PBS) and treatment groups (pre-oral, oral or intraperitoneal injection). Each group had 6 mice. The tumor size was measured once every three days until endpoint (35 days). After sacrificing the mice, tumor tissue was removed, sectioning and then analyzed by TUNEL or immunohistochemistry (IHC) assays. RESULTS: Metformin inhibited proliferation and colony formation of HSC-3, HSC-4 in a time- and dose-dependent manner. The cell proliferation was significantly reduced when treated with 5, 10, 20 and 40 mmol/L metformin for 48 and 72 hours (P < 0.05).The colony formation of OSCC cells treated with metformin for 72 hours in vitro had the same result. Treated with 2, 20 and 50 mmol/L metformin for 24 hours increased the ratio of G0/G1 1.2-1.8 fold compared with the control group on HSC-4 cell. The percentage of apoptosis cell rose from 10% (control) to around 30% (treatment) in vitro. Metformin also decreased the size of xenografts by 82.5% (pre-oral), 63.9% (oral), and 62.8% (oral or intraperitoneal injection). The percentage of apoptosis cell rose from lower than 10% (control) to 70% (pre oral), 50% (oral), and 25% (oral or intraperitoneal injection). The percentage of PCNA positive cell was lower than 60% (control group was normalized to 100%). CONCLUSIONS: Metformin could inhibit the growth of OSCC cell line (HSC-3, HSC-4) by reducing cell proliferation and increasing cell apoptosis in vitro and in vivo. Therefore metformin could be a potential new treatment candidate for human OSCC. PMID- 26359041 TI - [The risk factor for metastasis in Level IV in tongue cancer patients]. AB - OBJECTIVE: To investigate the risk factor for metastasis in Level IV of ipsilateral neck in tongue cancer patients. METHODS: A total of 248 tongue caner paitents (255 necks) that underwent radical neck dissection was enrolled in the study. Chi-square test and Logistic regression analysis were used to determine the factors associated with metastasis in Level IV. The variable included age, sex, growth type, T stage, histopathological grade, Level III involvement, number of positive lymph nodes in Levels I-III. RESULTS: Out of 147 cases (152 necks) with positive lymph node, 21 necks (8.2%, 21/255) had Level III involvement, and 2 necks (0.8%, 2/255) developed skip metastasis. Chi-square test showed that age (P = 0.020), Level III involvement (P = 0.000), number of positive Level (>= 2 Levels) in Levels I-III (P = 0.006), and number of positive lymph node (>= 3 nodes) in Levels I-III (P = 0.000) were identified as independent risk factor. Logistic regression analysis revealed that only Level III involvement (P = 0.003) was the risk factor for metastasis in Level IV. CONCLUSIONS: In tongue cancer patients, Level III involvement was a high risk factor for metastasis in Level IV. PMID- 26359042 TI - [Masticatory performance and assessment of life quality of children with ectodermal dysplasia after prosthetic rehabilitation]. AB - OBJECTIVE: To evaluate masticatory performance and life quality of children with ectodermal dysplasia (ED) after prosthetic rehabilitation. METHODS: Six children with ED received denture restoration and 18 healthy children were involved in this study. The surface electromyography (EMG) of masseter (MM) and anterior temporalis (TA) during clenching and chewing movement were recorded. The EMG amplitude, area, asymmetry index of total and activity index of MM/TA were compared at each stage. The masticatory efficiency was measured with spectrophotometer. The life quality was assessed using visual analogue scale questionnaire. RESULTS: The EMG amplitude of MM and TA during chewing in ED Group were 41.7% and 45.6% of the control group respectively, the area were 35.9% and 36.0% respectively. Significant difference in asymmetry index of total during clenching was observed between the two groups (P < 0.05) but not during chewing (P > 0.05). The differences of activity index of MM/TA during clenching and chewing between the two groups were not detected (P > 0.05). The masticatory efficiency of ED group was 67.2% of the control group. The score of chewing function in children with ED after prosthetic rehabilitation was three times higher than before, and no difference was present between the two groups (P > 0.05). CONCLUSIONS: Early prosthetic rehabilitation can significantly improve the masticatory performance and life quality of children with ED. PMID- 26359043 TI - [Distal movement of the mandibular dentition in the treatment of patients with Class III skeletal pattern]. AB - OBJECTIVE: To evaluate the outcome of patients with skeletal Class III malocclusion treated with extraction of mandibular third molars and distalization of molars using implant anchorage combined with MBT appliance. METHODS: Fifteen patients (mean age 24.0 +/- 5.8) with skeletal Class III malocclusion were selected. The mandibular third molars were extracted and the mandibular molars were moved distally using implant combined with MBT appliance. Cephalometric analysis was carried out before and after treatment. RESULTS: After active treatment, ANB, Wits distance, AB-NP and the distance between upper and lower lip position to SnPg' increased by 1.65 degrees +/- 1.04 degrees , (4.39 +/- 1.93) mm, 3.20 degrees +/- 1.61 degrees and (1.13 +/- 0.99) mm, respectively. The differences were statistically significant (P < 0.05). CONCLUSIONS: The skeletal Class III patients in the permanent dentition could be treated successfully with extraction of mandibular third molars and distalization of mandibular molars using implant anchorage combined with MBT appliance. The soft-tissue profile was improved. PMID- 26359044 TI - [Study of oral microbial adhesion and biofilm formation on the surface of nano fluorohydroxyapatite/polyetheretherketone composite]. AB - OBJECTIVE: To develop novel polyetheretherketone (PEEK) based nanocomposites which possess the favorable antibacterial property, and to investigate the oral microbial adhesion and biofilm formation on the surfaces of PEEK, nano fluorohydroxyapatite (n-FHA)-PEEK and nano-hydroxyaptite (n-HA)-PEEK. METHODS: The bacterial adhesion and biofilm formation on the surfaces of n-FHA-PEEK, n-HA PEEK were investigated via microbial viability assay kit and laser scanning confocal microscope (LSCM), respectively, with pure PEEK as control group. RESULTS: No significantly statistical difference were found in the bacterial adhesion amounts on the surfaces of n-FHA-PEEK, n-HA-PEEK and PEEK at 1 h and 4 h. However, the number of bacteria on the n-FHA-PEEK surface decreased dramatically at 2 h (0.496 +/- 0.008) compared with n-HA-PEEK groups (0.543 +/- 0.015, P < 0.01). Although the biofilms formation on surfaces observed by LSCM had similar morphology and thickness at 3, 7, 14 d, that on the n-FHA-PEEK surface showed the highest dead-to-live bacteria ratio among the three materials at 14 d. CONCLUSIONS: The combination of n-HA, especially for the n-FHA could inhibit the bacteria adhesion and accelerate the bacterial death, eventually may have an influence on the structure of biofilms and reduce the risk of peri implantitis. Therefore, n-FHA-PEEK nanocomposites presented a good prospect for clinical applications as dental implant materials. PMID- 26359045 TI - [Tissue engineered bone and dental implant in the repair of maxillary defect in two stages: a case report]. PMID- 26359046 TI - Illicit drug use and harms, and related interventions and policy in Canada: A narrative review of select key indicators and developments since 2000. AB - BACKGROUND: By the year 2000, Canada faced high levels of illicit drug use and related harms. Simultaneously, a fundamental tension had raisen between continuing a mainly repression-based versus shifting to a more health-oriented drug policy approach. Despite a wealth of new data and numerous individual studies that have emerged since then, no comprehensive review of key indicators and developments of illicit drug use/harm epidemiology, interventions and law/policy exist; this paper seeks to fill this gap. METHODS: We searched and reviewed journal publications, as well as key reports, government publications, surveys, etc. reporting on data and information since 2000. Relevant data were selected and extracted for review inclusion, and subsequently grouped and narratively summarized in major topical sub-theme categories. RESULTS: Cannabis use has remained the principal form of illicit drug use; prescription opioid misuse has arisen as a new and extensive phenomenon. While new drug-related blood borne-virus transmissions declined, overdose deaths increased in recent years. Acceptance and proliferation of - mainly local/community-based - health measures (e.g., needle exchange, crack paraphernalia or naloxone distribution) aiming at high-risk drug users has evolved, though reach and access limitations have persisted; Vancouver's 'supervised injection site' has attracted continued attention yet remains un-replicated elsewhere in Canada. While opioid maintenance treatment utilization increased, access to treatment for key (e.g., infectious disease, psychiatric) co-morbidities among drug users remained limited. Law enforcement continued to principally focus on cannabis and specifically cannabis users. 'Drug treatment courts' were introduced but have shown limited effectiveness; several attempts cannabis control law reform have failed, except for the recent establishment of 'medical cannabis' access provisions. CONCLUSIONS: While recent federal governments introduced several law and policy measures reinforcing a repression approach to illicit drug use, lower-level jurisdictions (e.g., provincial/municipal levels) and non-governmental organizations increasingly promoted social- and health-oriented intervention frameworks and interventions, therefore creating an increasingly bifurcated - and inherently contradictory - drug policy landscape and reality in Canada. PMID- 26359047 TI - Miraculous Meaning: Threatened Meaning Increases Belief in Miracles. AB - For many, religious belief is a source of meaning and a resource for coping with life stressors that have the potential to undercut meaning. In the present study, we sought to further probe the connection between religion and meaning by focusing on the potential for threatened meaning to inspire belief in miraculous testimonials. We threatened meaning with a meaninglessness manipulation and then had participants read testimonials in which people described miraculous experiences involving supernatural agents and rate the extent to which they believed these testimonials to be credible and true. Meaning threat, relative to a control condition, increased belief in miraculous stories. PMID- 26359048 TI - Depression and Dyspepsia: An Implication of Islamic Resources. AB - Depression is a common mental disorder and the leading cause of disability in the worldwide. Based on Islamic resources, indigestion and dyspepsia can lead to depression. In modern medicine, though many somatic diseases have been named as possible causes of depression, the effect of gastrointestinal disorders on depression is still an enigma. Therefore, the focus of this study is to explore the available scientific literature of modern medicine in order to find the footprint of effect of indigestion on depression. In this study, related articles were retrieved from PubMed, Ovid, Proquest and Magiran databases by using the Medical Subject Heading keywords "depression," "psychology," "dyspepsia" and "gastrointestinal diseases." In the next step, studies, which are exactly confirm the Islamic viewpoint, were selected from the retrieved articles. Only one prospective study in 2012 has stated that people with functional gastrointestinal disorders and without elevated levels of anxiety and depression at baseline had significantly higher levels of anxiety and depression at 12-year follow-up. Based on Islamic viewpoint, indigestion can lead to depression, but this aspect approved by only one 12-year prospective population-based study in our review. It seems that it is necessary to conduct complementary studies investigating this hypothesis. PMID- 26359049 TI - The Application of Ibadah (Worship) in Counseling: Its Importance and Implications to Muslim Clients. AB - Ibadah is one of the important components in Islamic teachings other than aqidah (belief) and akhlaq (moral). Its importance is determined through the purpose for creation of humans, namely to be devoted to Allah. In the context of counseling discipline, however, the element of ibadah or worship (submission) of Allah is not applied in the counseling process and is not recognized as one of the spiritual therapies able to help the client know his true potential in decision making and problem-solving. Hence, the purpose of this study is to determine the importance of applying ibadah in counseling and its implications to the client. This study selects survey research as the method to collect data from clients. A set of questionnaire instruments was constructed and distributed to 30 clients selected through convenience sampling. Data obtained from research questionnaire are then analyzed using descriptive statistical technique. Research outcome finds that application of ibadah is very important in counseling and has four implications for the client: the client is able to control his behavior, gain peace of mind, control his emotions and becomes increasingly diligent in ibadah. PMID- 26359050 TI - [The challenges faced in the field of trauma care in China]. AB - With the continuous development of China's urbanization and socio-economic, death and disability caused by trauma has increased prominently, and trauma has become the first cause of death in the people younger than 45 years old. Compared with the treatment of other diseases, China are facing many problems and challenges in terms of trauma treatment, specifically focused in three areas: First, the medical profession and society had not attach enough attention to trauma; Second, trauma centers in our country is insufficient; The level of trauma care vary greatly between different regions, the doctors and nurses commitment to trauma care lack of standardized training; Third, scientific treatment process and treatment system that compliance with international standards and meet the geographical features of China is insufficient. In view of the above situation and existing problems, learn from the successful experience of foreign countries, we think we should proceed from the following three aspects to change the status of China's treatment of trauma gradually: First of all, we should establish Traumatology that deals with the treatment of serious wounds and injuries. Secondly we should establish the right trauma care system that suitable for China's conditions; The third point is the establishment of trauma specialist training system composed by "basic training" and "targeted training"; Final we should establish severe trauma multidisciplinary treatment team model in the process of trauma care. Thereby improving our overall level of trauma treatment through above means, reduce the disability and mortality caused by trauma, thus promoting the development of trauma forward. PMID- 26359051 TI - [Tibiotalar or tibiocalcaneal arthrodesis using the ilizarov technique in the presence of infected nonunions of ankle joints]. AB - OBJECTIVE: To evaluate the results of managing the infected nonunions of distal tibial fractures combined with talar fracture and calcaneal fracture with tibial bone transport, tibiotalar or tibiocalcaneal arthrodesis using the hybrid external fixator. METHODS: A retrospective review of 26 patients who underwent either tibiotalar arthodesis or tibiocalcaneal arthodesis using an hybrid external fixator for infected nonunions of distal tibial fractures, talar and calcaneal fractures after tibial bone distraction was made. Each patient had a debridement of all infected and nonviable bones, the wound area were 2 cm*4 cm-4 cm*8 cm. The bony surfaces of distal tibia and talus were prepared for the fusion followed by application of an Orthofix's hybrid external fixator. RESULTS: The remaining 18 patients undertook debridement at the docking sites, and 14 of them had autogenous bone grafting. There was a mean follow-up of 32 months (22-38 months). All the patients had successful fusions. There were no recurrent deep infections or amputations. Two patients had 6 degrees of varus deformity at the docking site. CONCLUSION: Tibiotalar or tibiocalcaneal arthrodesis using the Ilizarov technique is viable alternative to amputation in patients with infected nonunions,especially if there is a large bone loss of the tibias, talus and calcaneus. PMID- 26359053 TI - [Abdominal aortic aneurysm treated by endovascular stent graft and conventional surgical repair for overweight and obesity patients: a comparison early result]. AB - OBJECTIVE: To investigate the outcomes in overweight and obesity patients with abdominal aortic aneurysm (AAA) treated with elective open or endovascular repair (EVAR). METHODS: The clinical data of 52 patients with AAA treated by EVAR (EVAR group, n=17) and conventional surgical repair (open group, n=54) were analyzed retrospectively. Overweight was defined as a body mass index (BMI) between 24 kg/m2 and 28 kg/m2, obesity was defined as a BMI 28 kg/m2. Patients' conditions, operative time, blood loss, function recovery and complications were compared. A two-tailed Student's t-test or rank sum test was used to compare measurement data between the two groups. chi2 test or Fisher exact probability test was used to compare quantitative data between the two groups. RESULTS: No significant difference were observed in gender, age, other disease, anesthesia risk category, aneurysm type, the maximum aneurysm diameter, and mortality rate between the groups (P>0.05). All patients had success of surgical procedures. Compared with open group the EVAR group had significant reductions in operative time ((449+/ 174) minuets vs. (140+/-36) minuets), blood loss ((1.8+/-1.9) L vs. (1.7+/-1.2) L), units of blood transfusion ((5.3+/-5.2) units vs. 0), intravenous fluids ((3.3+/-1.6) L vs. (1.6+/-1.6) L), need for ventilation ((26.2+/-10.6) hours vs. (2.3+/-1.4) hours), intensive care unit stay ((5.2+/-1.3) days vs. (1.4+/-0.5) days) and length of stay ((17+/-9) days vs. (7+/-3) days) (F=9.932 to 44.816, all P<0.05). Six cases of complications was observed in open group during perioperative, while 9 cases of complications were observed in EVAR group. The difference was significant (chi2=9.572, P=0.008) which open group was significantly higher than the EVAR group. Two patients died during perioperative in open group, however, the EVAR group had no deaths occurred. All complications were connected with the interventional technique. Endoleak was the chief complication after operation. After Follow-up the main complications of infection (n=2), wounds (n=2) and abdominal hernia (n=2) based for open group was observed, and the main complications for EVAR group was endoleak (1 case of type I, 3 cases of type II). CONCLUSION: EVAR may be preferable in overweight and obesity patients with AAA in the short term. PMID- 26359052 TI - [The clinical value of pancreatic fistula risk predicting system after pancreaticoduodenectomy]. AB - OBJECTIVE: To evaluate the clinical value of a preoperative predictive scoring system which was established by the National Cancer Center Hospital (NCCH) for the postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy. METHODS: The clinical data of 269 patients who underwent pancreaticoduodenectomy at the Affiliated Provincial Hospital of Anhui Medical University from February 2008 to February 2014 were studied retroprospectively. The five indexes which including gender, portal invasion, pancreatic cancer, main pancreatic duct index and intra abdominal fat thickness were calculated in the NCCH predictive score system. Patients with a score over 4 were defined as high risk of POPF, and those with score less than 4 were defined as low risk of POPF. Then the factors associated with POPF were analyzed by Logistic regression test. The enumeration data and measurement data were compared with chi2 test and t test. Risk factors for postoperative pancreatic fistula were analyzed through single factor and multiple factors Logistic regression analysis. The sensitivity and specificity of the predictive scoring system were determined by receiver operating characteristic (ROC) curve analysis. RESULTS: A total of 33 patients were diagnosed as POPF, including 15 in grade A, 11 in grade B and 7 in grade C. The univariate analysis showed that the factors associated with POPF are gender, total serum bilirubin level, pancreatic cancer, portal invasion, the pancreatic texture, main pancreatic duct diameter and the pancreaticojejunostomy. The multivariate analysis showed that gender, pancreatic texture, portal invasion and main pancreatic duct diameter were the independent risk factor of POPF. The rate of pancreatic fistula of high risk group was 53.8% (14/26), and the rate of pancreatic fistula of the low risk group was 7.8% (19/243). There were significant differences in the pancreatic fistula rate between the high risk and low risk of POPF (chi2=46.231, P<0.01). The results of ROC curve analysis showed that the sensitivity and specificity of the predictive scoring system were 87.9% and 94.1%, respectively. The area under the curve was 0.946 (95% CI: 0.895 0.997). CONCLUSIONS: The NCCH preoperative predictive scoring system could accurately predict the occurrence of POPF. While large, multicenter prospective randomized controlled trials is still needed to further confirm it. PMID- 26359054 TI - [Spatial relation study between the compressed spinal cord and the cervical pedicle]. AB - OBJECTIVE: To study the relationship between cervical pedicle and compressed spinal cord. METHODS: One hundred and five patients (53 male,52 female,age from 29 to 80 years) with cervical spondylotic myelopathy who needed surgery were included from December 2011 to January 2013 in Shengjing Hospital. Plain MRI scan was used for cross section of C4 - C7 vertebral bodies parallel to the axis of bilateral pedicle, and the images were sent to the workstation. PACS system was applied to measure the anatomical parameters related to the security of cervical pedicle screw, including the shortest distance from medial left/right cervical pedicle to the cervical spinal cord (LH/RH), and the smallest angle between the longitudinal axis of left/right cervical pedicle and the screw which was assumed to just touch the cervical spinal cord (LSA/RSA). All these data in each segment were classified according to compression or not:with compression and without compression. Twelve cases were selected and measured by MRI and 3D cervical CT for spinal canal width D, namely the straight-line distance between the medial margins of cervical pedicle. And the results of two methods were compared to see whether there were statistical differences. RESULTS: At C4, LH was (7.2+/-1.3) mm, RH was (6.7+/-1.4) mm, and the average was (6.9+/-1.4) mm; at C5, LH was (7.7+/-1.4) mm, RH was (6.7+/-1.4) mm, and the average was (7.2+/-1.5) mm; at C6, LH was (8.2+/-1.5) mm, RH was (6.9+/-1.3) mm, and the average was (7.5+/-1.5) mm; at C7, LH was (8.2+/-1.4) mm, RH was (7.3+/-2.1) mm, and the average was (7.7+/ 1.8) mm. At C4, LSA was 34.4 degrees +/-4.2 degrees , RSA was 34.4 degrees +/-5.2 degrees and the average angle was 34.4 degrees +/-4.7 degrees ; at C5, LSA was 35.9 degrees +/-5.2 degrees , RSA was 34.6 degrees +/-5.4 degrees and the average angle was 35.3 degrees +/-5.3 degrees ; at C6, LSA was 37.4 degrees +/ 4.8 degrees , RSA was 34.8 degrees +/-4.8 degrees and the average angle was 36.1 degrees +/-5.0 degrees ; at C7, LSA was 39.2 degrees +/-5.8 degrees , RSA was 37.1 degrees +/-5.2 degrees and the average angle was 38.1 degrees +/-5.6 degrees ; There were no statistically significant differences between segments with and without compression in H, SA and D (all P>0.05). CONCLUSIONS: There is security space between the medial vertebral pedicle and compressed spinal cord. There is individual variation in security space. It is very necessary to identify security space before surgery by MRI, emphasize individual procedure and avoid spinal cord injury. PMID- 26359055 TI - [Neurological complications of posterior vertebral column resection for severe rigid congenital spinal deformities]. AB - OBJECTIVE: To analyze the risk factors of neurological complications of posterior vertebral column resection in the treatment of severe rigid congenital spinal deformities. METHODS: The clinical data of 88 patients with severe rigid congenital spinal deformities who underwent PVCR in Department Of Orthopaedics, Xijing Hospital, Fourth Military Medical University from June 2007 to November 2012 were collected. There were 39 males and 49 females at the average age of 16.9 years (range 6-46 years). To measure the Cobb angle and balance at preoperative, postoperative and follow up, and to record the operation report, neurological complications and at follow up. The relevant factors of neurological complications were analyzed by one-way analysis, including: age, Cobb angle, operation time, body mass index, pulmonary function, blood volume loss, resection level, number of vertebrae fixed, number of vertebrae resected, usage of cage or titanium mesh, preoperative neurologic function, the type of deformity and combination of spinal canal deformity, and further analyzed by multiariable Logistic regression analysis. RESULTS: The average follow up was 42 months (range 19 to 83 months). The number of resected vertebrae average 1.3 (range 1 to 3), operative time average 502.4 min (range 165.0 to 880.0 min), estimate blood loss average 2,238 ml (range 100 to 11,500 ml) for an average 69.3% blood volume loss (range 9% to 299%). The average preoperative major coronal curve of 93.6 degrees corrected to 22.2 degrees , at the final follow-up, the coronal curve was 22.2 degrees with a correction of 76.8%. The average preoperative coronal imbalance (absolute value) was 2.5 cm decreasing to 1.3 cm at the final follow-up. The average preoperative major sagittal curve of 88.2 degrees corrected to 28.7 degrees , at the final follow-up, the sagittal curve was 29.2 degrees , average decrease in kyphosis of 59.0 degrees . The average preoperative sagittal imbalance (absolute value) was 3.1 cm decreasing to 1.2 cm at the final follow up. There were 12 patients (13.6%) developed a neurological complications. High rate of neurological complications was occurred in patients with operative time greater than 480 min, pulmonary dysfunction, blood volume loss greater than 50%, T7-T99 osteotomy and preoperative neurologic compromise (P=0.046, 0.000, 0.000, 0.033, 0.043). CONCLUSIONS: Posterior vertebral column resection can achieve satisfactory efficacy in treatment of severe spinal deformities. Pulmonary dysfunction and blood volume loss greater than 50% were significant risk factors of neurological complications. PMID- 26359056 TI - [The left ventricular assistance device was used for anomalous origin of the left coronary artery from the pulmonary artery in perioperative period]. AB - OBJECTIVE: To review the experience of left ventricular assistance device (LVAD) using for anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) in perioperative period. METHODS: There were 29 patients with ALCAPA underwent surgical repair from May 2006 to May 2013. The mean age was 6.5 months (ranging from 3.3 to 12.1 months). The mean weight was 6.2 kg (ranging from 4.1 to 9.5 kg). Diagnosis was established by echocardiography in all patients. There were clinical symptomatic of the severe heart dysfunction and ejection fraction were 23% to 45%. Mitral insufficiency was moderate to severe in 8 patients and less than moderate in others. Surgical methods included the intrapulmonary tunnel (Takeuchi procedure) of 4 cases, direct reimplantation of the left coronary artery onto the aorta of 6 cases and reimplantation by pericardiac patch enlarge of 19 cases. Valvuloplasty were performed in 5 patients with mitral severe insufficiency. Twenty-two patients were treated only by medicine therapy. LVAD was used in 7 patients: there were 3 patients with low blood pressure at the end of surgical repair and 4 patients with low cardio output within 24 hours postoperatively. RESULTS: Postoperatively, transesophageal echocardiography demonstrated that blood flow of the left coronary artery is fluently but left ventricular is also largement. The hemodynamic of 18 patients was stable in medicine group but 3 patients were sudden died of low cardiao output and ventricular fibrillation respectively. One patient was died of diffuse intravascular coagulation at the time of 72 hours after operation. The hemodynamic was stable in 6 patients in LVAD group and the devices after using time from 72 to 108 hours was taken down except one patient died of multi-organ dysfunction. The hospital mortality was 5/29 (17.2%). Nineteen survival (19/24) was followed up of 3.5 years (ranging from 1 to 7 years). Reoperations was performed for one patient with the supravalvar pulmonary stenosis due to the Takeuchi procedure 4 years postoperatively. Echocardiographic demonstrated that the blood flow of the left coronary artery are fluently. Mitral insufficiency was moderate in 2 cases, mild to moderate in 9 cases and mild in 8 cases. The ejection fraction value were 43% to 55% and apparent arrhythmia didn't occur. CONCLUSIONS: Although late results are satisfactory and left ventricular function always recovery, early mortality is higher even though the protective methods are carried out during the whole cardiopulmonary bypass procedure. In order to decrease the early mortality, heart function evaluation and LVAD should be used as an effective cardiac support technique to prevent heart failure in time. PMID- 26359057 TI - [Results and predictors of long-term outcomes of off-pump coronary artery bypass grafting: 2 831 cases from a single center]. AB - OBJECTIVE: To describe the long-term survival of off-pump coronary artery bypass grafting (CABG) and to analysis the risk factors of operative mortality and long term survival. METHODS: From January 2001 to December 2012, 2 831 patients undergoing off-pump CABG in Peking University People's Hospital, 2 099 cases (74.1%) of them were male, the average age was (63+/-9) years. The perioperative data was retrospectively collected. Binary Logistic regression was used to find the risk factors which affect the operative mortality. Follow-up evaluation was completed regularly. Kaplan-Meier survival curve, Log-rank test and Cox regression model were used to find out factors which affect the long-term result. RESULTS: Totally 2 831 patients underwent isolating off-pump CABG, in whom 45 patients died perioperative, 2 786 patients discharged successfully. Binary Logistic regression showed that sex (female) (chi2=4.4, OR=2.307, P=0.035), peripheral vascular disease (chi2=17.4, OR=6.616, P=0.000), New York Heart Association (NYHA) class grade>=3 (chi2=10.5, OR=3.491, P=0.001), ejection fraction<=40% (chi2=16.9, OR=5.230, P=0.000), emergency surgery (chi2=11.9, OR=5.127, P=0.001) are risk factors of operative mortality. The follow-up time was (74+/-44) months. Totally 107 patients were lost from follow-up, 109 patients died in follow-up. The survival rate at 1, 3, 5 , 8 and 10 years was 97.2%, 95.5%, 94.3%, 93.6%, 92.1%, respectively. Univariate analysis showed that age (>65 years), hypertension, renal insufficiency, peripheral vascular disease, history of myocardial infarction, NYHA class grade>=3 and emergency surgery were risk factors of the long-term survival (chi2=8.150 to 88.241, P<0.05). Cox regression analysis showed that age (>65 years) (chi2=12.1, RR=2.295, P=0.000), renal insufficiency (chi2=12.3, RR=3.160, P=0.000), peripheral vascular disease (chi2=42.5, RR=5.626, P=0.000), NYHA class grade>=3 (chi2=9.1, RR=1.994, P=0.002) and emergency surgery (chi2=5.5, RR=2.247, P=0.019) were independent risk factors that affect the long-term survival. CONCLUSIONS: Sex (female), peripheral vascular disease, NYHA class grade>=3, ejection fraction<=40%, emergency surgery are risk factors of operative mortality. Age (>65 years), renal insufficiency, peripheral vascular disease, NYHA class grade>=3 and emergency surgery are independent risk factors that affect the long-term survival. Off-pump CABG has favorable perioperative and long-term outcome, and it definitely is a very safe and effective technique for coronary artery revascularization. PMID- 26359058 TI - [Surgical management of infective endocarditis with cerebrovascular complications]. AB - OBJECTIVE: To investigate the result of surgical treatment of active infective endocarditis in patients with recent cerebrovascular events, and to evaluate the optimal indication and timing of surgical intervention. METHODS: The clinical data of 26 patients with cerebrovascular complications before surgery Between December 2007 and December 2013 were analyzed retrospectively. There were 17 male and 9 female patients, aged (42+/-14) years. Types of disease included single aortic valvular disease (n=8), single mitral valvular disease (n=12), multiple valvular disease (n=5), and aortic valvular disease with ventricular septal defect (n=1). Type of cerebrovascular complication included cerebral infarction (n=25) and cerebral hemorrhage (n=1). Thirty-one valves were involved in 26 patients, mechanical prosthetic valve replacement (n=25), bioprosthetic valve replacement (n=4), and mitral valve repair (n=2). RESULTS: The interval between onset of cerebrovascular event and surgical intervention was less than 14 days (n=3), 14 to 21 days (n=13), over 21 days (n=10), and the mean was (20+/-4) days. There were 33 vegetations found intraoperatively. The mean size of vegetations was (10+/-4) mm and 19 were found in mitral valve. Two patients died in hospital. One case relapsed after 1 year and underwent reoperation for prosthetic valve endocarditis. The remaining patients recovered with cardiac function of New York Heart Association class I to II after the period of 3 months to 5 years follow up. CONCLUSIONS: Appropriate surgery may effectively improve the outcome of IE patients with cerebrovascular complications. The surgical indications and risks of further neurologic deterioration after cardiac surgery should be assessed comprehensively before surgical intervention. PMID- 26359059 TI - [Laparoscopic radiofrequency ablation for centrally located renal tumors]. AB - OBJECTIVE: To study the safety and effectiveness of laparoscopic radiofrequency ablation for centrally located renal tumors. METHODS: From January 2009 to April 2013, thirteen patients who diagnosed as centrally located renal tumors were treated with laparoscopic radiofrequency ablation in the Department of Urology of Nanjing Drum Tower Hospital Affiliated to Nanjing University Medical School. All of the cases were T1aN0M0 stage, 9 patients were male, 4 were female, the mean age was 56 years (range, 38-73 years). All tumors were unilateral, eight lesions were in the left kidney and five in the right kidney. Intraoperative real-time ultrasound and temperature probes were used to guide the range of radiofrequency ablation. Ice saline was injected through ureteral catheter for cooling the collecting system. The postoperative serum creatinine and glomerular filtration rate (GFR) data were collected,all patients were followed up with enhanced CT or MRI.The pre- and post-operative date were compared by paired t test. RESULTS: All patients underwent laparoscopic radiofrequency ablation successfully. The mean operation time was (113+/-13) minutes and the mean blood loss was (99+/-23) ml. The mean pre- and post-operative serum creatinine was (71+/-11) umol/L and (74+/ 11) umol/L, the mean pre- and post-operative GFR was (49+/-8) ml/min and (45+/-7) ml/min. There was no significant statistic difference between pre-operation and post-operation (t=-1.371 and 1.986, P>0.05). The mean follow-up was 37 months, range 12-63 months. No evidence of local recurrence or distant metastasis was found. CONCLUSIONS: Laparoscopic radiofrequency ablation for T1aN0M0 centrally located renal tumors could be performed safely with good outcomes. Intraoperative real-time ultrasound and temperature probes are helpful to control the range of radiofrequency ablation. Physical cooling of renal collecting system could reduce the occurrence of postoperative hydronephrosis and leakage of urine. PMID- 26359060 TI - [Anterior interhemispheric approach through the lamina terminalis for large intra and extra-ventricular craniopharyngiomas]. AB - OBJECTIVE: To investigate the techniques and effect of surgical resection of large intra- and extra-ventricular craniopharyngiomas via anterior interhemispheric trans-lamina terminalis approach. METHODS: Fifty-two patients who were surgically treated for large intra- and extra-ventricular craniopharyngiomas were retrospectively analyzed. All patients underwent surgery via anterior interhemispheric trans-lamina terminalis approach. Of the 52 patients, 28 were male and 24 were female, with age ranging from 3 to 67 years (mean age 33.5 years). The maximum tumor diameter varied from 4.0 to 7.8 cm, with mean diameter of 5.1 cm. Contrast-enhanced MRI was underwent to determine the extent of tumor resection on the 1 to 3 months after surgery. RESULTS: Total removal of the lesion was achieved in 47 cases (90.4%), 5 patients underwent subtotal resection (9.6%). Division of the anterior communicating artery was performed in 6 patients with no early or late complications related to division of the artery. Visual acuity was preserved or improved in 44 patients (84.6%). Preservation of the pituitary stalk were achieved in 33 patients (63.5%). No surgery-related deaths occurred. The postsurgical follow-up period varied from 3 months to 68 months (mean 25.4 months). Twenty-three cases had endocrinological deficit and received some form of hormonal replacement after surgery. Permanent diabetes insipidus occurred in 18 cases. Three patients died and 6 patients suffered recurrence during the followed-up period. CONCLUSIONS: The anterior interhemispheric approach, with opening of the lamina terminalis, is a valid choice for large intra- and extra-ventricular craniopharyngiomas. These tumors can be removed without significant sequelae related to the surgical approach because optic nerves, optic chiasm, internal carotid artery, hypothalamic structures and pituitary stalk can be seen and effectively protected. PMID- 26359061 TI - [Old fracture]. AB - Old fracture generally refers to fractures for more than 3 weeks, and complications caused by delayed treatment or therapy: delayed union, malunion and nonunion of fractures. Delayed union means that fracture healing is not taking place within the expected time, but the definition of fracture nonunion is controversy. Delayed union and nonunion of fractures are caused by a variety of factors, unstable and blood supply of destroy are considered the most important factors. Because of substantial suffering about patients living, working and economics caused by delayed union and nonunion, early intervention is necessary. Treatment includes conservative and operative. Mechanical stimulation, physical treatment and bio-stimulation have been proven to promote healing of fractures, autogenous cancellous bone graft combined with strong fixation is the gold standard for surgery. Malunion means a consolidation of a fracture in a position of deformity and malalignment. Deformities are described in terms of abnormalities of length, angulation, rotation, and translation. The treatment of malunion is a lengthy and complex process and the main purpose is to relieve pain, restoring alignment and function. PMID- 26359062 TI - [Diagnosis and treatment of fracture delayed union and nonunion]. AB - Fracture nonunion is the cessation of a normal reparative process of fracture healing. With an incidence of 2.5%-4.4%, it is one of difficult problem for orthopedics surgeons. Definition, classification, treatment and causes of fracture nonunion are reviewed in this article. The therapeutic principles and methods are introduced systematically combined with causes of fracture nonunion. PMID- 26359063 TI - [Current treatment and progress of hepatocellular carcinoma with portal vein tumor thrombus]. AB - Portal venous tumor emboli is one of the important factors that affect the prognosis of patients with hepatocellular carcinoma (HCC). There are different characters of surgery, interventional therapy, radiation therapy, treatment of local damage, targeted therapy in the treatment of portal venous tumor emboli, but the effects are not ideal. Scholars at home and abroad are exploring a variety of treatment patterns in the treatment of portal venous tumor emboli, to achieve better effect.Predominantly surgical comprehensive treatment can excision of tumor and tumor emboli, improve liver function, improve the quality of survival, prolong survival time. But the operation risk is big. Mainly non surgical treatment has advantages of little trauma, less risk, and better local control of tumor emboli. But the efficiency, effect, alleviate period is ineffective. Therefore, the best treatment mode should be explored according to the different tumor emboli parting. PMID- 26359064 TI - [Nonarthroplasty methods for developmental dysplasia of the hip with complete dislocation at the age of 8-25 patients]. AB - It is a tough challenge treatment of complete dislocation from developmental dysplasia of the hip at the age of 8-25 patients. Although the procedure of total hip arthroplasty (THA) can improve joint function significantly, the failure rate still remains high. Hip arthrodesis remains a sensible and safe option. A stable and painless hip joint can be obtained without multiple operations. Ganz et al.had described a modified Colonna capsular arthroplasty and surgical hip dislocation with well joint functions, radiographic findings and the less complications of the femoral head osteonecrosis. There is a obvious advantage in postponing THA, and subsequent THA could be technically easier and safer in a dislocated hip. The procedure of pelvic support osteotomy, which is proposed by Ilizarov, combined two steps of femur osteotomy and femur lengthening, provides an effective treatment option for adolescent hip dysplasia or dislocation. By this procedure, the hip could be reserved, the limb length recovered and the gait improved significantly. Resection arthroplasty is a reliable method, by which 90% dysplasia patients received a painless joint and good functional outcomes. In view of certain drawbacks, it is used only as a salvage operation currently. This article reviews some alternative nonarthroplasty methods for developmental dysplasia of the hip with complete dislocation. Good clinical results can be obtained through strict indications and nice surgical skills. PMID- 26359065 TI - [Application and research advances of metabolomics in the field of orthopedics]. AB - Metabolomics is a subject of systematic, qualitative and quantitative analysis of all metabolites in all organisms, which is applied to finding biomarkers and studying pathogenesis of diseases. Study procedures of metabolomics include data acquisition by spectroscopic/spectrometric techniques, multivariate statistical analysis and projection of the acquired metabolomic information. In recent years, metabolomics have gained popularity in orthopedic field. Metabolomic study of osteoarthritis was firstly conducted and widely developed. Metabolite profiles of different samples, including serum/plasma, urine, synovial fluid and synovial tissue, were studied and dozens of differential metabolites and several disturbed metabolic pathways were found. In addition, metabolomic studies of osteoporosis, ankylosing spondylitis and bone tumors were also conducted, which identified many potential biomarkers and made further understanding of pathogenesis of corresponding disease. However, metabolomic studies in orthopedic field just begin. More orthopedic diseases will be researched thank to the satisfactory results of previous reports. PMID- 26359066 TI - Effects of Strength Training Using Unstable Surfaces on Strength, Power and Balance Performance Across the Lifespan: A Systematic Review and Meta-analysis. AB - BACKGROUND: The effectiveness of strength training on unstable surfaces (STU) versus stable surfaces (STS) or a control condition (CON; i.e., no training or regular training only) for strength, power and balance performance across the lifespan has not yet been investigated in a systematic review and meta-analysis. OBJECTIVE: The aims of this systematic review and meta-analysis were to determine the general effects of STU versus STS or CON on muscle strength, power and balance in healthy individuals across the lifespan and to investigate whether performance changes following STU are age specific. DATA SOURCES: A computerized systematic literature search was performed in the electronic databases PubMed and Web of Science from January 1984 up to February 2015. STUDY ELIGIBILITY CRITERIA: Initially, 209 articles were identified for review. Only controlled trials were included if they investigated STU in healthy individuals and tested at least one measure of maximal strength, strength endurance, muscle power, or static/dynamic balance. In total, 22 studies met the inclusion criteria. STUDY APPRAISAL AND SYNTHESIS METHODS: The included studies were coded for the following criteria: age, sex, training status, training modality, exercise and test modality. Effect size measures included within-subject standardized mean differences (SMDw) and weighted between-subject standardized mean differences (SMDb). Heterogeneity between studies was assessed using I2 and chi2 statistics. The methodological quality of each study was assessed using the Physiotherapy Evidence Database (PEDro) Scale. RESULTS: Our search failed to identify studies that examined the effects of STU versus STS or CON in children and middle-aged adults. However, four studies were identified that investigated the effects of STU versus CON or STS in adolescents, 15 studies were identified in young adults and three studies were identified in old adults. Compared with CON, STU produced medium effects on maximal strength in young adults and no effects to medium effects in old adults. In addition, large effects were detected on strength endurance in adolescents and in young adults; in old adults, a small effect was found. With regard to muscle power, medium effects were observed in young adults and small effects were observed in old adults. Further, large effects were found for static and dynamic balance in old adults, but only a small effect was found for dynamic balance in young adults. The comparison of STU and STS revealed inconsistent results as indicated by training-induced changes in favour of STU, as well as STS. Small to medium effects were found for maximal strength in adolescents in favour of STS, and small effects were found in young adults in favour of STU. With regard to strength endurance, large effects were found in adolescents in favour of STS and small effects were found in favour of STU. Additionally, we detected small effects in young adults in favour of STU. In terms of muscle power, no effects were observed in adolescents but medium effects were found in favour of STS in young adults. With regard to balance, small effects were detected in adolescents for static and dynamic balance in favour of STU. In young adults, small effects were found for static balance in favour of STS. With regard to dynamic balance, the analysis revealed small effects in young adults in favour of STU. LIMITATIONS: The quality of the included studies was rather low, with mean PEDro scores of 5.8, 4.0 and 5.0 for studies including adolescents, young adults and old adults, respectively. Further, trivial to considerable heterogeneity between studies (i.e., 0% <= I2 <= 96%) was detected. CONCLUSIONS: Compared with CON, STU is effective in improving muscle strength, power and balance in adolescents, young adults and old adults. However, inconsistent results were particularly found in adolescents and young adults when the specific effects of STU were compared with those of STS. We conclude that the performance of STU compared with STS has limited extra effects on muscle strength, power and balance performance in healthy adolescents and young adults. Given that our systematic search did not identify studies that examined the effects of STU versus STS in children, middle aged adults and old adults, further research of high methodological quality is needed to determine whether there are additive effects of STU as compared with STS in those age groups. PMID- 26359067 TI - Is the Wet-Bulb Globe Temperature (WBGT) Index Relevant for Exercise in the Heat? PMID- 26359068 TI - Centro-Apical Self-Organization of Organic Semiconductors in a Line-Printed Organic Semiconductor: Polymer Blend for One-Step Printing Fabrication of Organic Field-Effect Transistors. AB - Here we report the first demonstration for centro-apical self-organization of organic semiconductors in a line-printed organic semiconductor: polymer blend. Key feature of this work is that organic semiconductor molecules were vertically segregated on top of the polymer phase and simultaneously crystallized at the center of the printed line pattern after solvent evaporation without an additive process. The thickness and width of the centro-apically segregated organic semiconductor crystalline stripe in the printed blend pattern were controlled by varying the relative content of the organic semiconductors, printing speed, and solution concentrations. The centro-apical self-organization of organic semiconductor molecules in a printed polymer blend may be attributed to the combination of an energetically favorable vertical phase-separation and hydrodynamic fluids inside the droplet during solvent evaporation. Finally, a centro-apically phase-separated bilayer structure of organic semiconductor: polymer blend was successfully demonstrated as a facile method to form the semiconductor and dielectric layer for OFETs in one- step. PMID- 26359069 TI - [A new classification of pancreatic cancer to guide operative decisions and the comparison with the TNM stage]. AB - Despite the worldwide application of various terminological and classification systems used for pancreatic cancer, such as UICC classification and JPS classification based on the TNM system, however, little information on their use in operative decision-making is available. A new classification system according to the relationship with the tumor and key vasculature around the pancreas is described, and the pancreatic carcinomas are divided into eight types to provide operative decisions for different types of pancreatic cancer. Furthermore, the relationship between the classification system and TNM system is discussed. The new classification is the first time to discuss the classification for the operative decisions for the pancreatic cancer and this formalized type of approach may provide the best chance of achieving R0 resection and providing improved safety results. PMID- 26359070 TI - [Analysis of risk factors of Budd-Chiari syndrome complicated with hepatocellular carcinoma]. AB - OBJECTIVE: To investigate the risk factors of Budd-Chiari syndrome (B-CS) complicated with hepatocellular carcinoma (HCC). METHODS: The clinical data of 30 patients with B-CS complicated with HCC treated in the First Affiliated Hospital of Zhengzhou University from December 2012 to November 2014 were analyzed retrospectively, 106 another patients were selected randomly as control group in the same term. Gender, age, medical history, type of B-CS, hemoglobin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin, Child-Pugh classification, portal vein diameter, HBV infection and drinking history were recorded and analyzed between the two groups. Univariate analysis and unconditional Logistic regression model were performed to screen corresponding risk factors. Area under curve (AUC) was calculated according to receiver operator characteristic (ROC) curve to evaluate the diagnostic value of each indicator. RESULTS: Univariate analysis showed that there were no statistical differences in gender (chi2 =0.001), age (t=0.317), medical history (t=-0.906), type of B-CS (chi2 =2.894), ALT (t=-1.581), Child-Pugh classification (Z=-0.777), HBV infection (chi2 =0.016) and drinking history (chi2 =0.285) between the two groups (all P > 0.05), but the hemoglobin (t=3.370) and albumin (t=2.152) in HCC group were lower and AST (t=-2.425) and portal vein diameter (t=-2.554) were higher than that in the other group, and the differences were statistically significant (all P <0.05). The results of unconditional Logistic regression model analysis indicated that hemoglobin, AST and portal vein diameter were independent risk factors of B-CS complicated with HCC (OR=0.972, 1.015, 1.206; P=0.004, 0.022, 0.012). ROC curve analysis indicated that the AUC of AST, hemoglobin and portal vein diameter was 0.704, 0.324 and 0.624, the predicate value was, in order, AST, portal vein diameter, hemoglobin. CONCLUSION: Hemoglobin, AST and portal vein diameter are independent risk factors of B-CS complicated with HCC. PMID- 26359071 TI - [Retrospective analysis of 856 cases with stage 0 to III rectal cancer underwent curative surgery combined modality therapy]. AB - OBJECTIVE: To investigate the survival and prognostic factors of stage 0 to III rectal cancer in 10 years. METHODS: Clinical data and follow-up of 856 rectal cancer patients with stage 0-III underwent curative surgery from January 2000 to December 2010 were retrospective analyzed. There were 470 male and 386 female patients, with a mean age of (58 +/- 12) years. Kaplan-Meier method was used to analyze the overall survival and disease free survival. Log-rank test was used to compare the survival between groups. Cox regression was used to analyze the independent prognostic factors of rectal cancer. RESULTS: The patients in each stage were stage 0 with 18 cases, stage I with 209 cases, stage II with 235 cases, and stage III with 394 cases. All patients received curative surgery. There were 296 patients evaluated as cT3, cT4 and any T with N+ received preoperative radiotherapy. 5.4% patients got pathological complete response (16/296), and the recurrence rate was 4.7% (14/296). After a median time of 41.7 months (range 4.1 to 144.0 months) follow-up, the 5-year overall survival rate in stage 0 to I of was 91.0%, stage II 86.2%, and stage III 60.0%, with a significant difference (P=0.000). The cumulative local recurrence rate was 4.8% (41/856), of which 70.7% (29/41) occurred within 3 years postoperatively, 97.6% (40/41) in 5 years. The cumulative distant metastasis rate was 16.4% (140/856), of which 82.9% (129/140) occurred within 3 years postoperatively, 96.4% (135/140) in 5 years. The incidence of abnormal imaging findings was significantly higher in pulmonary than liver and other sites metastases (75.0% vs. 21.7%, chi2 =25.691, P=0.000). The incidence of CEA elevation was significantly higher in liver than lung and other sites metastases (56.8% vs. 37.8%, chi2 =25.691, P=0.000). Multivariable analysis showed that age (P=0.015, HR=1.385, 95% CI: 1.066 to 1.801), surgical approach (P=0.029, HR=1.337, 95% CI: 1.030 to 1.733), differentiation (P=0.000, HR=1.535, 95% CI: 1.222 to 1.928), TNM stage (P=0.000, HR=1.349, 95% CI: 1.260 to 1.444) and lymphovascular invasion (P=0.001, HR=1.715, 95% CI: 1.258 to 2.342) are the independent prognostic factors for rectal cancer. CONCLUSIONS: Age, surgical approach, differentiation, TNM stage and lymphovascular invasion are independent prognostic factors for rectal cancer. Preoperative evaluation and combined modality therapy can significant reduce the local recurrence and improve overall survival for rectal cancer patients. PMID- 26359072 TI - [The prognostic impact of preoperative PET-CT on postoperative recurrence for completely resected stage I non-small cell lung cancer]. AB - OBJECTIVE: To analyze the prognostic impact of preoperative (18)F fluorodeoxyglucose (FDG) PET-CT on postoperative recurrence in patients with completely resected stage I non-small cell lung cancer (NSCLC). METHODS: The clinic data of 182 patients with stage I NSCLC who underwent (18)F-FDG PET-CT scan before surgical resection between June 2005 and June 2012 were reviewed retrospectively. There were 121 male and 61 female patients, with an average age of 68 years (range from 34 to 85 years). The pathological stage was I A in 98 patients, I B in 84 patients; the histology were adenocarcinoma in 137 patients, squamous cell carcinoma in 35 patients, and others in 10 patients. Clinicopathological factors including gender, age, smoking history, SUV(max), surgical procedure, pathological features and adjuvant chemotherapy were evaluated to identify the independent factors predicting postoperative recurrences by univariate and multivariate analysis. The survivals were calculated by the Kaplan-Meier method and differences in variables were analyzed by the Log-rank test. RESULTS: The postoperative recurrence rate was 15.9%. The univariate analysis identified that the SUV(max) (t=3.278, P<0.001), p-stage (chi2 =5.204, P=0.026), blood vessel invasion (chi2 =5.333, P=0.027) and visceral pleural invasion (chi2 =7.697, P=0.009) are factors for predicting postoperative recurrence. Only SUV(max) was found to be a significant independent factor according to multivariate analysis (HR=1.068, 95%CI: 1.015 to 1.123, P=0.001). The study population was stratified into three groups by SUV(max), patients with SUV(max) > 5.0 had significantly higher risk of recurrence (23.9%) than those with 2.5 < SUV(max) <= 5.0 (15.0%) and SUV(max) <= 2.5 (7.3%) (P=0.043); patients with SUV(max) <= 2.5 had significantly better 5-year recurrence-free survival rate (90.9%) than those with 2.5 < SUV(max) <= 5.0 (82.7%) and SUV(max) <= 2.5 (71.0%) (P=0.030). There was a trend toward higher probability of blood vessel invasion (chi2 =20.267, P < 0.001), visceral pleural invasion (chi2 =6.185, P=0.045) and pathological stage I B (chi2 =13.589, P=0.001) with increased SUV(max). CONCLUSIONS: Preoperative SUV(max) of primary tumor is a predictor of postoperative relapse for stage I NSCLC after surgical resection. Therefore, it can contribute to the risk stratification for patients with the same pathological stage and selecting the optimal postoperative follow-up and therapeutic strategy. PMID- 26359073 TI - [Short-term outcomes of minimally invasive Ivor Lewis esophagectomy for locally advanced esophageal cancer]. AB - OBJECTIVE: To describe the technique for minimally invasive Ivor Lewis esophagectomy (MIILE) and to evaluate the feasibility, safety and the short-term clinical outcomes of this approach. METHODS: The clinical data of 309 patients with locally advanced esophageal cancer who received Ivor Lewis esophagectomy between October 2011 and October 2013 was analyzed retrospectively. Of those 309 patients, 112 underwent MIILE and 197 underwent open Ivor Lewis esophagectomy (OILE). The clinicopathologic factors, operational factors and postoperative complications of the two groups were compared by t test and chi2 test. RESULTS: The two groups were similar in terms of gender, age, American Society of Anesthesiologists grade, tumor location, preoperative staging and incidence of comorbidities (P>0.05). The MIILE approach was associated with a significant decrease in surgical blood loss ((186 +/- 45) ml vs. (198 +/- 47) ml, t=2.086, P=0.039), chest tube duration ((9 +/- 5) days vs. (11 +/- 6) days, t=2.760, P=0.005) and postoperative stay ((12 +/- 6) days vs. (14 +/- 7) days, t=2.932, P=0.005) relative to the OILE approach. There was no significant difference between the two groups in the number of total lymph nodes dissected or the stations of the total lymph nodes dissected (P>0.05). The postoperative in hospital mortality and total morbidity did not differ between the two groups (P>0.05). The MIILE approach was associated with significantly fewer wound infections than the OILE approach (0 vs.4.6%, P=0.029). CONCLUSION: Our MIILE technique for locally advanced esophageal cancer can be safely and effectively performed for intrathoracic anastomosis during esophageal surgeries with favorable early outcomes. PMID- 26359074 TI - [Characteristics and risk factors of lymph node metastasis in pN1 stage esophageal squamous cell carcinoma]. AB - OBJECTIVE: To analyze the pattern and the clinicopathologic risk factors of lymph node metastasis (LNM) in pN1 stage esophageal squamous cell carcinoma. METHODS: Clinical data of 181 patients (154 male and 27 female patients, aging from 38 to 84 years) who underwent esophagectomy during January 2005 and December 2008 were reviewed, including 69 cases through left thoracotomy and 112 cases through right thoracotomy. All patients underwent systematic lymphadenectomy. The risk factors related to lymph node metastasis were analyzed by chi2 test and Logistic regression analysis. RESULTS: The relatively highest LNM site were middle and lower thoracic paraesophageal (38.4%), right and left cardiac (35.3%) and the left gastric artery (38.8%). The LNM of middle and lower thoracic paraesophageal was correlated with T stage (chi2 =11.754, P=0.009). A correlation was also found among the LNM of upper mediastinum and the location of tumor (P=0.039). The T stage (chi2 =8.694, P=0.034) and TNM stage (chi2 =6.906, P=0.032) were the risk factors of the LNM of middle and lower mediastinum. The risk factors of the LNM of abdomen were the location of tumor, the length of tumor, T stage and TNM stage (chi2 =5.713 to 16.749, P>0.05). Multivariate analysis showed that the location of tumor is the independent risk factors for the abdominal lymph node metastasis. CONCLUSIONS: The relatively highest LNM sites are correlated with the location of tumor, T stage, the length of tumor and TNM stage. According to the risk factors of LNM, the relatively highest LNM sites should be mainly swept. PMID- 26359075 TI - [Clinical features and risk factors of anastomotic leakage after radical esophagectomy]. AB - OBJECTIVE: To analyze the clinical features and risk factors of anastomotic leakage after radical esophagectomy of esophageal carcinoma. METHODS: The clinical data of 547 esophageal cancer patients underwent radical esophagectomy in Tianjin Medical University Cancer Hospital from January 2012 to December 2013 was analyzed retrospectively. There were 421 male and 126 female patients, with a median age of 65 years (ranging from 29 to 82 years). There were 155 cases of upper esophageal carcinoma, 340 cases of middle esophageal carcinoma and 52 cases of lower esophageal carcinoma. The surgical procedures included 41 cases completed through Sweet, 145 cases completed through McKeown, 279 cases completed through Ivor Lewis, 82 cases completed through minimally invasive esophagectomy. Moreover, 24 of 547 cases underwent preoperative neoadjuvant radiochemotherapy. chi2 test and Cox's proportional hazards regression model were used for univariate analysis and multivariate analysis of the risk factors of postoperative anastomotic leakage. RESULTS: Twenty-seven of 547 cases with esophagectomy occurred anastomotic leakage and the incidence rate was 4.94% (27/547). One of 27 cases died and the mortality rate was 3.70% (1/27). The time of anastomotic leakage found was 4 to 45 days, with a median time of 10 days. There were 0 case of early leakage, 20 cases of mid-term leakage, 7 cases of late leakage. Three of 27 cases with anastomotic leakage had tracheoesophageal fistula, while 3 cases had contralateral pleural fistula. As to the incidence rate of anastomotic leakage, there was statistically significant difference between cervical anastomotic leakage (8.14%, 18/221) and intrathoracic anastomotic leakage (2.76%, 9/326) (chi2 =7.41, P=0.000), among Sweet (4.88%, 2/41), McKeown (9.66%, 14/145), Ivor Lewis (2.51%, 7/279) and MIE (4.88%, 4/82) (chi2 =21.48, P=0.000), and between with (16.67%, 4/24)? and without (4.40%, 23/523) neoadjuvant radiochemotherapy (chi2 =9.20, P=0.000). The multivariate analysis showed that anastomotic site (HR=2.594, P=0.048), surgical approach (HR=5.689, P=0.003) and preoperative neoadjuvant radiochemotherapy (HR=3.604, P=0.027) are independent risk factors for anastomotic leakage after esophagectomy. CONCLUSIONS: The mid-term anastomotic leakage after esophagectomy occurs higher. McKeown is a main surgical procedure and neoadjuvant radiochemotherapy is an important factor for the anastomotic leakage. PMID- 26359076 TI - [Effects of two analgesic regimens on the postoperative analgesia and knee functional recovery after unilateral total knee arthroplasty-a randomized controlled trial]. AB - OBJECTIVE: To evaluate the efficacy of continuous femoral block on the postoperative analgesia and functional recovery after total knee arthroplasty (TKA). METHODS: Two hundreds and eighty patients who underwent TKA were randomized into two groups:the group receiving continuous femoral block (CFNB) and the group receiving patient controlled intravenous analgesia (PCIA), each group included 140 participants. Femoral nerve block with ropivacaine by ultrasonic guidance was performed in group CFNB and group PCIA were administrated with patient controlled intravenous analgesia. Numerical rating scale (NRS) scores at rest and in motion at 24, 48, 72 h, 3, 6 and 12 months postoperatively, also the NRS scores at hospital discharge were recorded. The incidence of moderate-severity pain, as well as the degree of knee flexion and the WOMAC scores at 3, 6 and 12 months after surgery were analyzed. The rescue analgesic administration and analgesia-related adverse effects were also recorded. Data were expressed as mean+/- standard deviation (SD) for normally distributed continuous variables and total number (percent frequency) for categorical variables. If non-normally distributed, data were expressed median inter-quartile range. Student's t-test, Wilcoxon rank test were used to compare results for continuous variables, when appropriate. Chi-square test was used to compare results for categorical variable, Fisher exact test was used for categorical variables when the number of event was less than 5. RESULTS: NRS scores of group CFNB in motion was 3 (3-4) at discharge time, and 3 (2-4), 3 (2-3) at 3 months and 6 months postoperatively, while the scores of group PCIA was 4 (4-4), 3 (3 4), 3 (3-4), respectively. And at rest, NRS scores of group CFNB was 3 (2-3), 1 (1-2), 1 (1-1) at discharge time, and 3, 6 months postoperatively. Compared with group PCIA, NRS scores in motion of group CFNB at discharge time (Z=-5.174, P<0.05) and 3 months (Z=2.308, P=0.021), as well as 6 months postoperatively (Z= 2.495, P=0.013), were significantly lower,also for the NRS scores at rest (Z= 2.405, P=0.016; Z=-4.360, P<0.05; Z=-9.268, P<0.05). The degree of knee flexion of group CFNB at 3 and 6 months postoperatively was 92 (88-97), 103 (99-106), while the degree of knee flexion of group PCIA was 89 (86-95), 100 (97-105); the WOMAC scores of group CFNB at 3 and 6 months postoperatively was 21 (18-26), 18 (16-22), while the scores of group PCIA was 24 (20-27), 21 (17-24). WOMAC scores of group CFNB was lower compared with group PCIA at 3 (Z=-2.467, P=0.014) and 6 (Z=-2.537, P=0.011) months postoperatively while the degree of knee flexion of group CFNB was higher (Z=-2.175, P=0.030; Z=-2.471, P=0.013). Moreover, the frequency of bolus and frequency of rescue of group CFNB was 2.3 and 0.6, while the frequency of group PCIA was 2.6 and 1.1, the frequency of bolus and frequency of rescue were lower in group CFNB (t=-2.984, P=0.003; t=-3.213, P=0.002). The incidence of adverse events such muscle weakness of low limbs,nausea and vomiting were similar in two groups (P>0.05). CONCLUSION: CFNB can alleviate the postoperative pain after TKA with safety, help improving the short-middle-term functions of knee and quality of patients' lives. PMID- 26359077 TI - [The value of 3 dimensional-fat suppression-spoiled gradient-recalled acquisition sequence on single compartment osteoarthritis for unicompartmental arthroplasty preoperative assessment]. AB - OBJECTIVE: To analyze the 3 dimensional-fat suppression-spoiled gradient-recalled acquisition (3D-FS-SPGR) sequence in the diagnosis of knee articular cartilage injury. METHODS: A total of 56 knee osteoarthritis patients (26 males, 30 females, ages 52-73 years, mean 61.8 years) treated in Department of Orthopedics, Chinese People's Liberation Army General Hospital between June 2013 and May 2014 were involved in this study. All patients underwent knee MRI, plus 3D-FS-SPGR sequence, arthroscopic exploration, and in contrast to the results of MRI results analysis, evaluation 3D-FS-SPGR and conventional sequence of cartilage damage consistent with the arthroscopic accuracy. RESULTS: Divided 56 knee joints into 336 cartilage articular surface, included 55.1% normal articular surface, 21.4% early osteoarthritis and 23.5% advanced osteoarthritis. The accordance of 3D-FS SPGR sequence grading and arthroscopic was 90.2%. The sensitivity of 3D-FS-SPGR sequence was 93.1%, specificity was 98.3%, and Kappa value was 0.849. The sensitivity of T2WI sequence was 84.4%, specificity was 96.9%, and the Kappa value was 0.671. CONCLUSION: For unicompartment osteoarthritis , MRI 3D-FS-SPGR sequence is effective in sensitivity and specificity of cartilage damage. PMID- 26359078 TI - [Retrospective study for the risk factors of the early complication after carotid endarterectomy]. AB - OBJECTIVE: To review the influencing factors of the early complication after carotid endarterectomy (CEA). METHODS: Retrospective analysis of clinical data of 509 cases received CEA in Xuan Wu Hospital of Capital Medical University, Liaocheng People's Hospital and Dalian Central Hospital from January 2001 to December 2011. There are 422 male patients and 72 female patients among the 494 patients, 15 patients underwent CEA by stages. The patients were between 35-84 years old,and the mean age was (64 +/- 9) years. The complications within 30 days after CEA were analyzed, and find the risk factors for the major adverse events. Chi-square analysis was performed to analyze the correlation between the each variable of the basic characteristics of population, clinical features and intraoperative data and early adverse events after CEA. Logistic regression analysis was used to assess the relationship between a variety of factors and the postoperative complications within 30 days. RESULTS: Technical complete rate of 98.6%, 7 cases of near-total occlusion patients could not been recanalized. Major complications in 30 days after CEA occurred in 20 cases (3.9%), including 6 cases of deaths (1.2%), 9 cases of cerebral infarction (1.8%) and 5 cases of cerebral hemorrhage (1.0%). Secondary complications occurred in 120 cases (23.6%). Univariate analysis showed modified Rankin scale (mRS) >= 3 on the incidence of early postoperative complication had significantly difference (chi2 =20.517, P < 0.01), multivariate logistic regression analysis revealed that smoking (OR=2.667, 95% CI: 1.048-6.791, P=0.040) and mRS >= 3 (OR=8.690, 95% CI: 3.279-23.031, P=0.000) were the significant predictors of 30 days of the end event. CONCLUSION: The complications after CEA are uncommon, the security is proved. Smoking and mRS >= 3 can increase the risk of CEA. PMID- 26359079 TI - [Short-term outcome of single stenting technique for unruptured wide-necked tiny aneurysms of the anterior circulation]. AB - OBJECTIVE: To evaluate the short-term outcome of single stenting technique for unruptured, wide-necked, tiny aneurysms of the anterior circulation. METHODS: Eleven unruptured, wide-necked, tiny aneurysms of the anterior circulation were treated by a single stent deployed in the parent artery between January 2008 and July 2013 in Department of Neurosurgery in Beijing Hospital. The maximum diameter of the aneurysms ranged from 2.0 to 3.0 mm, mean (2.4 +/- 0.4) mm, and the dome to-neck ratios were all <= 1.2. The locations were clinoid segment of internal carotid artery (n=2), posterior communicating artery origin (n=4), anterior choroidal artery origin (n=2) and middle cerebral artery bifurcation (n=3). All internal carotid aneurysms were located in the medial and/or ventral wall of the internal carotid artery. The rate of aneurysm obliteration and rupture during follow-up was obtained by repeat angiography and clinic or telephone interview respectively. RESULTS: Sole stent placement in the parent artery was intentionally performed for nine aneurysms, while attempt of coiling after stent deployment for the other two aneurysms failed due to unsuccessful microcatherization. Ten stents were successfully deployed, of which one was used to treat two tandem lesions simultaneously. Only one aneurysm became smaller immediately postprocedure. No perioperative complications occurred. Angiographic follow-up after a mean period of (13 +/- 6) months (range 8-24 months) revealed that 8 aneurysms did no change in size, 2 became smaller and only one was totally occluded. Asymptomatic in-stent stenosis of the parent artery was found in all 3 shrinking or occluded aneurysms. No aneurysm rupture was observed in the clinical follow-up. CONCLUSION: For those unruptured, wide-necked, tiny aneurysms arising at branching sites in the anterior circulation, single stenting technique seems to be a safe alternative treatment, while the short-term rate of aneurysm occlusion is low. PMID- 26359080 TI - [Influence of clinical factors on Gleason score upgrade in patients undergoing radical prostatectomy]. AB - OBJECTIVE: To evaluate clinical factors affecting Gleason score upgrade in patients receiving radical prostatectomy (RP). METHODS: A total of 322 patients with prostate cancer who received RP from January 2012 to December 2013 at Department of Urology at Fudan University Shanghai Cancer Center were included, and their data of age, body mass index (BMI), prostate-specific antigen (PSA), prostate volume, percentage core, clinical staging, pathological characteristics, biopsy Gleason score and RP Gleason score were analyzed. Differences in categorical variables and continuous variables were compared using chi2 tests and Student's t-test, respectively. Unconditional multiple logistic regression was used to estimate OR and 95% CI of the association of Gleason score upgrade with clinical factors. RESULTS: Gleason score upgrade occurred in 107 of 322 (33.3%) patients. There was no difference in age, BMI and clinical staging between the two groups. Compared with patients without Gleason score upgrade, higher levels of PSA (chi2 =6.740, P=0.034), smaller prostate volume (t=3.481, P=0.002) and elevated percentage core (t=-2.097, P=0.037) were observed in patients with Gleason score upgrade. In addition, lymph node metastasis (chi2 =4.193, P=0.041) and extracapsular extension (chi2 =4.747, P=0.029) were more common in patients with Gleason score upgrade. After adjusting for potential confounders, PSA levels (OR=2.451, 95% CI: 1.290-4.660), prostate volume (OR=0.982, 95% CI: 0.969-0.995) and percentage core (OR=2.756, 95% CI: 1.033-7.357) were independent predictors for Gleason score upgrade. CONCLUSION: Gleason score upgrade happens at a relatively high rate. PSA levels, prostate volume and percentage core are important factors affecting Gleason score upgrade. PMID- 26359081 TI - [The effect of blood volume change on the accuracy of pulse contour cardiac output]. AB - OBJECTIVE: To study the accuracy of pulse contour cardiac output (PCCO) during blood volume change. METHODS: Hemorrhagic shock model was made in twenty dogs followed by volume resuscitation. Two PiCCO catheters were placed into each model to monitor the cardiac output (CO). One of catheters was used to calibrate CO by transpulmonary thermodilution technique (COTP) (calibration group), and the other one was used to calibrate PCCO (none-calibration group). In the hemorrhage phase, calibration was carried out each time when the blood volume dropped by 5 percents in the calibration group until the hemorrhage volume reached to 40 percent of the basic blood volume. Continuous monitor was done in the none-calibration group.Volume resuscitation phase started after re-calibration in the two groups. Calibration was carried out each time when the blood equivalent rose by 5 percents in calibration group until the percentage of blood equivalent volume returned back to 100. Continuous monitor was done in none-calibration group. COTP, PCCO, mean arterial pressure (MAP), systemic circulation resistance (SVR), global enddiastolic volume (GEDV) were recorded respectively in each time point. RESULTS: (1) At the baseline, COTP in calibration group showed no statistic difference compared with PCCO in none-calibration group (P >0.05). (2) In the hemorrhage phase, COTP and GEDV in calibration group decreased gradually, and reached to the minimum value (1.06 +/- 0.57) L/min, (238 +/- 93) ml respectively at TH8. SVR in calibration group increased gradually, and reached to the maximum value (5 074 +/- 2 342) dyn . s . cm-5 at TH6. However, PCCO and SVR in none calibration group decreased in a fluctuating manner, and reached to the minimum value (2.42 +/- 1.37) L/min, (2 285 +/- 1 033) dyn . s . cm-5 respectively at TH8. COTP in the calibration group showed a significant statistic difference compared with PCCO in the none-calibration group at each time point (At TH1-8, t values were respectively -5.218, -5.495, -4.639, -6.588, -6.029, -5.510, -5.763 and -5.755, all P < 0.01). From TH1 to TH8, the difference in percentage increased gradually. There were statistic differences in SVR at each time point between the two groups (At TH1 and TH4, t values were respectively 2.866 and 2.429, both P < 0.05, at TH2 - TH3 and TH5 - TH8, t values were respectively 3.073, 3.590, 6.847, 8.425, 6.910 and 8.799, all P < 0.01). There was no statistic difference in MAP between the two groups (P > 0.05). (3) In the volume resuscitation phase, COTP and GEDV in the calibration group increased gradually. GEDV reached to the maximum value ((394+/-133) ml) at TR7, and COTP reached to the maximum value (3.15 +/- 1.42) L/min at TR8. SVR in the calibration group decreased gradually, and reached to the minimum value (3 284 +/- 1 271) dyn . s . cm-5 at TR8. However, PCCO and SVR in the none-calibration group increased in a fluctuating manner. SVR reached to the maximum value (8 589 +/- 4 771) dyn . s . cm-5 at TR7, and PCCO reached to the maximum value (1.35 +/- 0.70) L/min at TR8. COTP in the calibration group showed a significant statistic difference compared with PCCO in the none-calibration group at each time point (At TR1-8, t values were respectively 8.195, 8.703, 7.903, 8.266, 9.600, 8.340, 8.938, 8.332, all P < 0.01). From TR1 to TR8, the difference in percentage increased gradually. There were statistic differences in SVR at each time point between the two groups (At TR1, t value was -2.810, P < 0.05, at TR2-8, t values were respectively -6.026, 6.026, -5.375, -6.008, -5.406, -5.613 and -5.609, all P < 0.05). There was no statistic difference in MAP between the two groups (P > 0.05). CONCLUSION: PCCO could not reflect the real CO in case of rapid blood volume change, which resulting in the misjudgment of patient's condition. In clinical practice, more frequent calibrations should be done to maintain the accuracy of PCCO in rapid blood volume change cases. PMID- 26359082 TI - [Pathology, imaging and treatment of rare types of intracranial aneurysms]. AB - The formation mechanisms of rare intracranial aneurysms are various, which lead to various kinds of treatment methods. The present article summarized the pathogenesis, pathologic changes in vascular walls and imaging features of rare intracranial aneurysms including segmental ectasia, aneurysms with dissection, aneurysms with intramural hemorrhage, mycotic aneurysms, aneurysms related to HIV, neoplastic aneurysms and traumatic aneurysms through literature review. PMID- 26359083 TI - Elephant resource-use traditions. AB - African elephants (Loxodonta africana) use unusual and restricted habitats such as swampy clearings, montane outcrops and dry rivers for a variety of social and ecological reasons. Within these habitats, elephants focus on very specific areas for resource exploitation, resulting in deep caves, large forest clearings and sand pits as well as long-established and highly demarcated routes for moving between resources. We review evidence for specific habitat exploitation in elephants and suggest that this represents socially learned cultural behaviour. Although elephants show high fidelity to precise locations over the very long term, these location preferences are explained neither by resource quality nor by accessibility. Acquiring techniques for exploiting specific resource sites requires observing conspecifics and practice and is evidence for social learning. Elephants possess sophisticated cognitive capacities used to track relationships and resources over their long lifespans, and they have an extended period of juvenile dependency as a result of the need to acquire this considerable social and ecological knowledge. Thus, elephant fidelity to particular sites results in traditional behaviour over generations, with the potential to weaken relationships between resource quality and site preferences. Illustrating the evidence for such powerful traditions in a species such as elephants contributes to understanding animal cognition in natural contexts. PMID- 26359084 TI - An enzymatic method for determination of azide and cyanide in aqueous phase. AB - A halohydrin dehalogenase (HHDH-PL) from Parvibaculum lavamentivorans DS-1 was characterized and applied to determine azide and cyanide in the water. In this methodology, HHDH-PL catalysed azide and cyanide to react with butylene oxide and form corresponding beta-substituted alcohols 1-azidobutan-2-ol (ABO) and 3 hydroxypentanenitrile (HPN) that could be quantitatively detected by gas chromatograph. The detection calibration curves for azide (R(2)=0.997) and cyanide (R(2)=0.995) were linear and the lower limits of detection for azide and cyanide were 0.1 and 0.3mM, respectively. Several other nucleophiles were identified having no effect on the analysis of azide and cyanide, excepting nitrite which influenced the detection of cyanide. This was the first report of a biological method to determine the inorganic azide and cyanide by converting them to the measurable organics. PMID- 26359085 TI - Discovery of a monophagous true predator, a specialist termite-eating spider (Araneae: Ammoxenidae). AB - True predators are characterised by capturing a number of prey items during their lifetime and by being generalists. Some true predators are facultative specialists, but very few species are stenophagous specialists that catch only a few closely related prey types. A monophagous true predator that would exploit a single prey species has not been discovered yet. Representatives of the spider family Ammoxenidae have been reported to have evolved to only catch termites. Here we tested the hypothesis that Ammoxenus amphalodes is a monophagous termite eater capturing only Hodotermes mossambicus. We studied the trophic niche of A. amphalodes by means of molecular analysis of the gut contents using Next Generation Sequencing. We investigated their willingness to accept alternative prey and observed their specific predatory behaviour and prey capture efficiency. We found all of the 1.4 million sequences were H. mossambicus. In the laboratory A. amphalodes did not accept any other prey, including other termite species. The spiders attacked the lateral side of the thorax of termites and immobilised them within 1 min. The paralysis efficiency was independent of predator:prey size ratio. The results strongly indicate that A. amphalodes is a monophagous prey specialist, specifically adapted to feed on H. mossambicus. PMID- 26359086 TI - MicroRNA-9 regulates osteoblast differentiation and angiogenesis via the AMPK signaling pathway. AB - MiR-9 has been found to be involved in the repair of spinal cord injury and regulates the proliferation and differentiation of mesenchymal stem cells. However, the role of miR-9 in repair of bone defects has not been well studied. The current study was designed to investigate its role and potential underlying mechanism in regulating osteoblast differentiation and angiogenesis. After treating the murine pre-osteoblast cell line MC3T3-E1 with BMP2, miR-9 expression was obviously down-regulated. Following transfection with miR-9 mimics, its overexpression enhanced the differentiation of MC3T3-E1 cells into osteoblasts as evidence that miR-9 up-regulated the mRNA levels of osteoblast differentiation related protein, as well as increased differentiation and mineralization of osteoblasts. Further functional analysis has shown that miR-9 overexpression effectively increased human umbilical vein endothelial cell proliferation. Moreover, miR-9 up-regulation promoted cell migration, VEGF, and VE-cadherin concentrations, as well as tube formation in vitro. The mechanistic assay demonstrated that overexpression of miR-9-induced activation of the AMPK signaling pathway. Taken together, our findings suggested that miR-9 overexpression promoted osteoblast differentiation and angiogenesis via the AMPK signaling pathway, representing a novel and potential therapeutic target for the treatment of bone injury-related diseases. PMID- 26359087 TI - Diazoxide preconditioning of endothelial progenitor cells from streptozotocin induced type 1 diabetic rats improves their ability to repair diabetic cardiomyopathy. AB - Type 1 diabetes mellitus (DM) is a strong risk factor for the development of diabetic cardiomyopathy (DCM) which is the leading cause of morbidity and mortality in the type 1 diabetic patients. Stem cells may act as a therapeutic agent for the repair of DCM. However, deteriorated functional abilities and survival of stem cells derived from type 1 diabetic subjects need to be overcome for obtaining potential outcome of the stem cell therapy. Diazoxide (DZ) a highly selective mitochondrial ATP-sensitive K(+) channel opener has been previously shown to improve the ability of mesenchymal stem cells for the repair of heart failure. In the present study, we evaluated the effects of DZ preconditioning in improving the ability of streptozotocin-induced type 1 diabetes affected bone marrow-derived endothelial progenitor cells (DM-EPCs) for the repair of DCM in the type 1 diabetic rats. DM-EPCs were characterized by immunocytochemistry, flow cytometry, and reverse transcriptase PCR for endothelial cell-specific markers like vWF, VE cadherin, VEGFR2, PECAM, CD34, and eNOS. In vitro studies included preconditioning of DM-EPCs with 200 MUM DZ for 30 min followed by exposure to either 200 MUM H2O2 for 2 h (for oxidative stress induction) or 30 mM glucose media (for induction of hyperglycemic stress) for 48 h. Non-preconditioned EPCs with and without exposure to H2O2 and 30 mM high glucose served as controls. These cells were then evaluated for survival (by MTT and XTT cell viability assays), senescence, paracrine potential (by ELISA for VEGF), and alteration in gene expression [VEGF, stromal derived factor-1alpha (SDF-1alpha), HGF, bFGF, Bcl2, and Caspase-3]. DZ preconditioned DM-EPCs demonstrated significantly increased survival and VEGF release while reduced cell injury and senescence. Furthermore, DZ preconditioned DM-EPCs exhibited up-regulated expression of prosurvival genes (VEGF, SDF-1alpha, HGF, bFGF, and Bcl2) on exposure to H2O2, and VEGF and Bcl2 on exposure to hyperglycemia while down regulation of Caspase-3 gene. Eight weeks after type 1 diabetes induction, DZ preconditioned, and non preconditioned DM-EPCs were transplanted into left ventricle of diabetic rats (at a dose of 2 * 10(6) DM-EPCs/70 MUl serum free medium). After 4 weeks, DZ preconditioned DM-EPCs transplantation improved cardiac function as assessed by Millar's apparatus. There was decrease in collagen content estimated by Masson's trichrome and sirius red staining. Furthermore, reduced cell injury was observed as evidenced by decreased expression of Caspase-3 and increased expression of prosurvival genes Bcl2, VEGF, and bFGF by semi-quantitative real-time PCR. In conclusion, the present study demonstrated that DZ preconditioning enhanced EPCs survival under oxidative and hyperglycemic stress and their ability to treat DCM. PMID- 26359089 TI - Use of Fixed Combination Therapies to Improve Blood Pressure Control in the Clinical Management of Hypertension: A Key Opportunity. PMID- 26359088 TI - Widdrol-induced lipolysis is mediated by PKC and MEK/ERK in 3T3-L1 adipocytes. AB - Obesity is a serious medical condition causing various diseases such as heart disease, type-2 diabetes, and cancer. Fat cells (adipocytes) play an important role in the generation of energy through hydrolysis of lipids they accumulate. Therefore, induction of lipolysis (breakdown of lipids into fatty acids and glycerol), is one of the ways to treat obesity. In the present study, we investigated the lipolytic effect of widdrol in 3T3-L1 adipocytes and its mechanism. Widdrol considerably increased the amount of glycerol released from 3T3-L1 adipocytes into the medium in a time- and dose-dependent manner. To determine the mechanism of this effect, we investigated the alterations in glycerol release and protein expression in 3T3-L1 adipocytes treated with widdrol alone or widdrol and inhibitors of proteins involved in the cAMP-dependent pathway or cAMP-independent PKC-MAPK pathway, which are known to induce lipolysis in adipocytes. The adenylyl cyclase inhibitor SQ-22536, PLA2 inhibitor dexamethasone, PI3K inhibitor wortmannin, and PKA inhibitor H-89, which were used to investigate the involvement of the cAMP-dependent pathway, did not affect the lipolytic effect of widdrol. Widdrol-induced phosphorylation of PKC, MEK, and ERK, which are related to the PKC-MAPK pathway, and their phosphorylation was inhibited by their inhibitors (H-7, U0126, and PD-98059, respectively). Moreover, the increase in glycerol release induced by widdrol was almost completely blocked by PKC, MEK, and ERK inhibitors. These results suggest that widdrol induces lipolysis through activation of the PKC-MEK-ERK pathway. PMID- 26359090 TI - [Interleukin-37 inhibits the motility and migration of mouse splenic dendritic cells]. AB - OBJECTIVE: To investigate the effect of interleukin-37 (IL-37) on the motility and migration of mouse splenic dendritic cells (DCs). METHODS: Magnetic bead cell sorting was used to isolate mouse splenic DCs, and flow cytometry was used to analyze the purity. DCs were visualized in real time by PerkinElmer laser confocal microscopy and analyzed by Volocity image analysis software. The alteration of chemokine (C motif) receptor 1 (XCR1) mRNA was revealed by microarray analysis and confirmed by real-time PCR and flow cytometry. Migration ability of DCs was detected by Transwell(TM) migration assay. RESULTS: The purity of isolated DCs was over 95%. The treatment of IL-37 reduced the velocity of DCs mobility, decreased XCR1 expression and depressed the cell migration ability. CONCLUSION: IL-37 can inhibit the motility and migration of mouse splenic DCs. PMID- 26359091 TI - [TLR4 promotes the activation of B cells in beta2GP1-immunized mice]. AB - OBJECTIVE: To investigate the effect of Toll-like receptor 4 (TLR4) on B cell activation in beta2-glycoprotein I (beta2GP1)-immunized mouse models. METHODS: The healthy TLR4+/+ C3H/HeN mice and TLR4-/- C3H/HeJ mice were randomly divided into two groups: beta2GP1 group and normal saline (NS) group. The mice were immunized with human beta2GP1 or equal amount of NS. The primary immunization was done by subcutaneous multi-point injection. The booster immunization was performed by intraperitoneal injection and the last immunization by intravenous injection. The titer of anti-beta2GP1 antibody in mouse sera was evaluated by indirect ELISA. HE staining was used to observe the changes of mouse germinal centers. The expression of CD40 ligand (CD40L) in the germinal centers was detected by immunohistochemistry. And the levels of co-stimulatory molecules CD80 and CD86 in the spleen were determined by flow cytometry. RESULTS: The high titer of anti-beta2GP1 antibody could be detected in mouse sera following immunization with beta2GP1. And the titer of the antibody in TLR4+/+ C3H/HeN mice was higher than that in TLR4-/- C3H/HeJ mice. Compared with NS group, the CD40L, CD19+CD80+ cells and CD19+CD86+ cells in C3H/HeN and C3H/HeJ mice were significantly up regulated by the treatment of beta2GPI, and the cell numbers in the C3H/HeJ mice were lower than those in the C3H/HeN mice. The germinal centers in beta2GP1 immunized mice were bigger and more than those in NS group, and the number of the germinal centers in TLR4+/+ C3H/HeN mice was more than that in TLR4-/- C3H/HeJ mice. CONCLUSION: TLR4 plays an important role in the process of B cell activation in beta2GP1-immunized mouse models. PMID- 26359092 TI - [Construction and identification of eukaryotic expression vectors of IKKalpha carrying Ser176/180 phosphorylation site mutants]. AB - OBJECTIVE: To construct eukaryotic expression vectors of the inhibitor of nuclear factor Kappa-B kinasealpha (IKKalpha) containing Ser176/180 phosphorylation site mutants. METHODS: Using PCR, we amplified two IKKalpha gene fragments, one containing Ser176/180 site mutants and non-sense mutation KpnI and the other with non-sense mutation KpnI. They were subjected to double enzyme digestion, HindIII/KpnI and KpnI/EcoRI, respectively, and then subcloned into pEGFP that had also digested with HindIII/EcoRI beforehand. The location of pEGFP-IKKalpha (kinase activity, KA)/(kinase death, KD) fusion protein in the eukaryocytes and their effects on P65 nuclear translocation were observed under a confocal microscope. The fusion protein expressions were detected by Western blotting. RESULTS: Sequencing analysis verified the fidelity of all plasmid DNA constructs. PEGFP-IKKalpha KA was mainly located in nucleus and cytoplasm, and regulated P65 nuclear shuttling. In contrast, pEGFP-IKKalpha KD was mostly localized in cytoplasm, and did not initiate P65 nuclear translocation. Western blotting confirmed the expressions of the fusion proteins. CONCLUSION: The eukaryotic expression vectors pEGFP-IKKalpha KA/KD were successfully constructed and well expressed in the eukaryocytes. The fusion proteins were located in different parts of the cells and exerted different effects on P65 nuclear translocation. PMID- 26359093 TI - [Establishment and identification of Jurkat cell xenograft mouse models with over expression of C-terminal Src kinase binding protein]. AB - OBJECTIVE: To establish xenograft mouse models of Jurkat T-leukemia cells over expressing C-terminal Src kinase binding protein (CBP). METHODS: The 5-week-old female BALB/c-nu mice were randomly divided into blank control group, normal Jurkat cell control group, empty virus-transfected Jurkat cell control group and CBP over-expression model group, 5 mice in each group. The mice were subcutaneously injected 1*10(7)/0.1 mL Jurkat cells in axillary area. The tumor tissues of mouse models were weighed and then subjected to HE staining to observe the pathological changes of tumor tissues. The proliferation of Jurkat cells in the peripheral blood of mice was detected by flow cytometry, and the interleukin 2 (IL-2) levels in mouse sera were determined with ELISA. RESULTS: The volume of tumor tissues in the CBP over-expression model group was smaller than that in the control groups, so was the mass of tumor tissues. HE staining showed the proliferation of Jurkat cells in tumor tissues of the model group. The proliferation rate of Jurkat cells in the peripheral blood and IL-2 levels in the sera of the CBP over-expression model group were lower than those in the normal Jurkat cell control group and the empty virus-transfected Jurkat cell control group. CONCLUSION: The mouse models of Jurkat T-leukemia cells over-expressing CBP have been established successfully. Up-regulated CBP has inhibitory effects on the proliferation of Jurkat cells and IL-2 secretion. PMID- 26359095 TI - [Establishment of RAW264.7 cell strain stably expressing RFP-GFP-LC3]. AB - OBJECTIVE: To establish murine macrophage RAW264.7 cell strain with stable expression of red fluorescent protein-green fluorescent protein-microtubule associated protein light chain 3 (RFP-GFP-LC3). METHODS: A lentiviral vector containing RFP-GFP-LC3 gene was constructed and then packaged in HEK293T cells with the packaging plasmids. The viral supernatant was collected to infect RAW264.7 cells. The RAW264.7 cell strain with stable expression of RFP-GFP-LC3 was screened with puromycin and analyzed with flow cytometry and fluorescent microscopy for infection efficiency. The number of RFP-GFP-LC3 puncta was observed using florescence microscopy following starvation treatment. RESULTS: The recombinant lentivirus pLV-CMV-RFP-GFP-LC3 was successfully constructed. The RAW264.7 cells with stable expression of RFP-GFP-LC3 were obtained by viral infection and puromycin screening. Fluorescent microscopy and flow cytometry demonstrated the expression rates of RFP and GFP reached to 100%. The number of autophagic puncta significantly increased after starvation treatment. CONCLUSION: The RAW264.7 cell strain with stable expression of RFP-GFP-LC3 has been successfully constructed, which provides a reliable cellular platform for autophagy research. PMID- 26359094 TI - [Increased expressions of TLR4 and related proinflammatory signaling molecules in the renal tissues of obese mice induced by high-fat diet]. AB - OBJECTIVE: To investigate the expressions of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and nuclear factor kappaBp65 (NF-kappaBp65) in the renal tissues of obese mice induced by high-fat diet (HFD). METHODS: Forty five C57BL/6 male mice (8 weeks old) were randomized into HFD group (n=39) and control group (n=6). The mice of the HFD group were fed high-fat and high-glucose diet for 20 weeks, and the others were given the normal diet instead. The body mass was measured weekly. At the end of the 20th week, one-third mice of the HFD group with the highest mass gain were classified as diet-induced obese (DIO) mice (n=13). The DIO mice and control mice were then sacrificed and tissues were collected for further use. The white adipose tissues (epididymal and perirenal fat pads) were removed and weighed. The levels of the serum creatinine (Cre), blood urea nitrogen (BUN) and lipopolysaccharide (LPS) were measured. The morphology of the renal tissues in both groups was studied by HE staining and microscopy. The levels of TLR2, TLR4, MyD88, NF-kappaBp65 and tumor necrosis factoralpha (TNF-alpha) mRNAs in the renal tissues were detected by the real-time quantitative PCR (qRT-PCR), and the levels of TLR4, MyD88 and NF-kappaBp65 proteins were determined by Western blotting. RESULTS: Compared with the control group, the serum LPS level showed significantly increased in DIO mice; however, no difference was found between the two groups in the serum Cre and BUN as well as in renal morphological structure. What's more, except that TLR2 mRNA level was not significantly different between the two groups, the mRNA levels of TLR4, MyD88, NF-kappaBp65 and TNF-alpha in the renal tissues of the DIO mice were significantly higher than those in the control group, and the protein levels of TLR4, MyD88 and NF-kappaBp65 in the renal tissues of the DIO mice were also elevated significantly. CONCLUSION: The levels of TLR4 and related proinflammatory signaling molecules increased in the renal tissues of obese mice induced by high-fat diet. PMID- 26359096 TI - [IL-18 and TNF-alpha promote the expression of IL-18Rbeta in 3T3-L1 adipocytes and RAW264.7 macrophages]. AB - OBJECTIVE: To explore the effects of interleukin 18 (IL-18) and tumor necrosis factor alpha (TNF-alpha) on the expression of IL-18 receptor beta (IL-18Rbeta) in 3T3-L1 adipocytes and RAW264.7 macrophages. METHODS: The level of IL-18Rbeta was determined by reverse transcription PCR and Western blotting in both 3T3-L1 adipocytes and RAW264.7 macrophages after processed by different concentrations of IL-18 and TNF-alpha. RESULTS: The level of IL-18Rbeta mRNA and protein significantly increased in 3T3-L1 adipocytes after treated with 10 ng/mL, 100 ng/mL TNF-alpha. The expression of IL-18Rbeta was also raised in RAW264.7 macrophages after treated with 10 ng/mL, 100 ng/mL IL-18. CONCLUSION: IL-18Rbeta could be up-regulated by IL-18 or TNF-alpha in 3T3-L1 adipocytes and RAW264.7 macrophages. IL-18 may be an important factor involved in the inflammation of adipose tissues in diabetes and obesity. PMID- 26359097 TI - [miR-199a-5p inhibits the proliferation of rat airway smooth muscle cells and the expression of hypoxia inducible factor 1 alpha under hypoxia conditions]. AB - OBJECTIVE: To investigate the expression of miR-199a-5p in airway smooth muscle cells (ASMCs) of rats in normoxia and hypoxia and its role in the regulation of proliferation and the expression of hypoxia inducible factor 1 alpha (HIF-1alpha) of ASMCs. METHODS: ASMCs were prepared by means of adherent culture in vitro. After ASMCs were cultured under normoxia and hypoxia conditions for 24 hours, the content of miR-199a-5p was detected by real-time quantitative PCR (qRT-PCR). The mimic or inhibitor of miR-199a-5p were artificially synthesized and transferred into ASMCs in hypoxia via liposomes. The expressions of miR-199a-5p and HIF 1alpha mRNA were detected by qRT-PCR. Western blotting and CCK-8 assay were applied to detect the expression levels of HIF-1alpha protein and the proliferation of ASMCs, respectively. RESULTS: Compared with the normoxia group, hypoxia significantly promoted cell proliferation and increased the levels of HIF 1alpha mRNA and protein. The level of miR-199a-5p decreased in the hypoxia group compared with the normoxia group. The proliferation rate of ASMCs under hypoxia conditions was significantly attenuated by transfection of miR-199a-5p mimic, while it was significantly lifted by transfection of miR-199a-5p inhibitor. Compared with control group, the expression of HIF-1alpha protein was reduced in the mimic group and raised in the inhibitor group. There was no significant difference in the content of HIF-1alpha mRNA among groups under hypoxia conditions. CONCLUSION: miR-199a-5p can inhibit the proliferation of ASMCs and the expression of HIF-1alpha protein in vitro under hypoxia conditions. PMID- 26359098 TI - [GPER silence inhibits the stimulation of growth and inhibition of apoptosis induced by tamoxifen in breast cancer-associated fibroblasts]. AB - OBJECTIVE: To construct a lentiviral vector (Lenti-GPER-shRNA) targeting G protein coupled estrogen receptor (GPER) and explore the role of GPER in the effect of tamoxifen on cell proliferation and apoptosis in breast cancer associated fibroblasts (BCAFs). METHODS: The target sequence of GPER gene and negative control were cloned into lentiviral vectors. The recombinant lentivirus and control were extracted after HEK293T cells were transfected with the recombinant vector and helper vectors. After infection of BCAFs with the GPER lentiviral vector under the best interfering condition, GPER expression was detected by real-time quantitative PCR and Western blotting. BCAFs were divided into negative control group, GPER-RNAi group, negative control combined with tamoxifen (10(-8) mmol/L) group and GPER-RNAi combined with tamoxifen (10(-8) mmol/L) group. CCK-8 assay was used to detect the proliferation and annexin V fluorescein isothiocyanate/propidium iodide (annexin V-FITC/PI) combined with flow cytometry was used to detect the apoptosis of BCAFs after the treatment of tamoxifen. RESULTS: Lenti-GPER-shRNA significantly interfered the expression of GPER in BCAFs. Tamoxifen promoted the growth of BCAFs, which could be attenuated by knockdown of GPER. Moreover, the apoptosis of BCAFs was reduced by tamoxifen, which was also reversed by knockdown of GPER. CONCLUSION: Lenti-GPER-shRNA could effectively silence the GPER expression in BCAFs. The ability of tamoxifen to accelerate cell proliferation and decrease cell apoptosis could be weakened by knockdown of GPER. PMID- 26359099 TI - [MTA1-specific shRNA inhibits the growth and metastasis of mouse xenograft of laryngeal squamous cell carcinoma]. AB - OBJECTIVE: To observe the effect of metastasis-associated gene 1 (MTA1) on the growth and metastasis of laryngeal squamous cell carcinoma in nude mice using RNA interference technology (RNAi). METHODS: Lentiviral vector of short hairpin RNA (shRNA) targeting MTA1 was constructed and packaged to transfect Hep-2 cells. Hep 2 cells transfected with scramble shRNA and MTA1 shRNA were injected into the paw pad of nude mice (n=5 per group). Nine weeks after modeling of the lymphatic metastasis of laryngeal carcinoma, the mice were sacrificed, and tumor tissues and inguinal lymph node were harvested to be subjected to HE staining, reverse transcription PCR and Western blotting. RESULTS: The gene screening showed the lentiviral vector of MTA1 shRNA was constructed successfully, and those tumor cells were transplanted and grew well in all mice. The size of tumor in the mice of MTA1 shRNA tansfected group was obviously smaller compared to the scramble shRNA transfected group at the same time point. No inguinal lymph node metastasis was found in the mice of MTA1 shRNA group. In contrast, the tumor cells were seen in the inguinal lymph nodes of the scramble shRNA infected mice. Reverse transcription PCR and Western blotting showed that the mRNA and protein levels of MTA1, beta-catenin, matrix metalloproteinase-9 (MMP-9), cyclin D1 were obviously reduced in MTA1 shRNA infected mice compared with the scramble shRNA infected mice. CONCLUSION: The inhibition of MTA1 gene could depress the growth and metastasis of laryngeal squamous cell carcinoma in nude mice. PMID- 26359100 TI - [Biphasic pulsed electrical stimulation promotes the differentiation of adipose derived stem cells into cardiomyocyte-like cells]. AB - OBJECTIVE: To design a biphasic pulsed electrical stimulation (BPES) system for cardiac tissue engineering and investigate the effect of BPES on the cardiomyocyte-like differentiation of adipose-derived stem cells (ADSCs) in vitro. METHODS: ADSCs were isolated and cultivated from Sprague Dawley rats. Surface protein expression was detected by flow cytometry to identify the cell phenotype. The multi-differentiation potential of ADSCs was verified by adipogenic and osteogenic inducers. The cells of the third passage were randomly divided into 2 groups: BPES group was subjected to BPES 24 hours after the cells were plated in 6-well culture plates, and BPES was set as 2 ms square pulses delivered at 2 Hz, 2 V voltage amplitude, and lasted 2 hours per day, for 3, 4 or 7 days. The culture medium was replaced every 3 days. Control group was cultured with the same condition but without BPES. The cell morphology was observed under an inverted phase-contrast microscope. Cell proliferation was evaluated by the MTT assay. The expression of cardiac-specific homeobox Nkx-2.5 and connexin 43(CX43) was determined by immunofluorescence cytochemistry. RESULTS: The flow cytometry proved that the isolated cells were ADSCs. Oil red O staining showed the fat droplets in the cytoplasm of ADSCs after adipogenic induction. alkaline phosphatase and Von Kossa staining showed calcium nodes in the ADSCs after osteogenic induction. No obvious changes were found in the proliferation of ADSCs. The levels of Nkx-2.5 and CX43 proteins were significantly higher in the BPES group than in the control group. CONCLUSION: BPES system we designed for tissue engineering could promote the differentiation of ADSCs into cardiomyocyte like cells in vitro. PMID- 26359101 TI - [Application of molecular chaperones to soluble expression of e23sFv/His fusion proteins]. AB - OBJECTIVE: To explore the feasibility of applying molecular chaperones to the soluble expression of e23sFv/His fusion proteins. METHODS: The molecular chaperone plasmid pGro7 or pKJE7 was transformed into BL21 (DE3) competent cells together with the prokaryotic expression vector harboring His-tagged e23sFv. The soluble expression of e23sFv/His proteins was induced at 16 degrees C. The yield and antigen-binding activity of the soluble products were compared with those of the insoluble products conventionally purified from inclusion bodies. RESULTS: Both the overall yield and the purification ratio of soluble e23sFv/His proteins were relatively lower. The binding affinity of the soluble products to immobilized HER2 was not superior to that of the insoluble products from inclusion bodies. CONCLUSION: The molecular chaperone plasmids pGro7 and pKJE7 partially facilitate the soluble expression of e23sFv/His proteins, but both the yield and the purification ratio are still limited. PMID- 26359102 TI - [Prokaryotic expression, purification and activity detection of the extracellular and intracellular domains of human IGF1R beta subunit]. AB - OBJECTIVE: To construct the prokaryotic expression vectors of extracellular domain (beta-ED) and intracellular protein kinase domain (beta-PKD) of insulin like growth factor 1 receptor beta (IGF1R-beta) subunit, purify the fusion proteins GST-IGF1R beta-ED and GST-IGF1R beta-PKD, and detect their activities. METHODS: Human GST-IGF1R beta-ED and GST-IGF1R beta-PKD coding regions were amplified from human mammary cDNA library by PCR and cloned into the prokaryotic expression vector pGEX-KG. The fusion proteins GST-IGF1R beta-ED and GST-IGF1R beta-PKD were expressed in E.coli Rossate and purified by GST-Sepharose 4B beads. The expression of the fusion proteins were detected by Western blotting. The interactions of the proteins with mediator of epidermal growth factor receptor-2 (ERBB2)-driven cell motility (MEMO) protein were identified by GST pull-down assay. RESULTS: GST-IGF1R beta-ED and GST-IGF1R beta-PKD recombinant plasmids were successfully cloned. Double enzyme digestion and sequencing confirmed that the inserted fragments were identical to the target ones. The fusion proteins were successfully induced in Rossate and Western blotting showed the expression as expected. GST pull-down assay revealed that GST-IGF1R beta-PKD could interact with MEMO in vitro. CONCLUSION: GST-IGF1R beta-ED and GST-IGF1R beta-PKD were successfully cloned and purified. In addition, GST-IGF1R beta-PKD could interact with MEMO in vitro, which demonstrated the good activity of the purified proteins. PMID- 26359103 TI - [Inducing effects of different microenvironments on the differentiation of mouse induced pluripotent stem cells into neuron-like cells]. AB - OBJECTIVE: To investigate the effects of different microenvironments on the differentiation of mouse induced pluripotent stem cells (iPSCs) into neuron-like cells. METHODS: Mouse iPSCs were cultured in suspension and became embryoid bodies (EBs), and then the EBs were randomly divided into all-trans-retinoic acid (ATRA) group, brain slice co-culture group, and brain tissue homogenate supernatant group. The above three groups were induced to differentiate into neuron-like cells. Morphological changes were observed under an inverted microscope. Immunofluorescence staining technology was used for cell identification. The expressions of nestin, microtubule-associated protein 2 (MAP2) and glial fibrillary acidic protein (GFAP) were detected by Western blotting. RESULTS: The three different culture conditions could all induce mouse iPSCs to differentiate into neuron-like cells. These neuron-like cells could be marked by neuron markers like nestin and MAP2. The levels of nestin, MAP2 and GFAP proteins in the ATRA group were significantly higher than those in both the brain slice co-culture group and the brain tissue homogenate supernatant group, but there was no significant difference between the brain slice co-culture group and the brain tissue homogenate supernatant group. CONCLUSION: Both brain slice microenvironment and brain tissue homogenate supernatant can induce the differentiation of mouse iPSCs into neuron-like cells, but the effect is inferior to ATRA. PMID- 26359104 TI - [Increased expression of IL-16 in mouse skin allograft]. AB - OBJECTIVE: To detect the expression of interleukin 16 (IL-16) in skin allografts of recipient mice and the serum level of IL-16. METHODS: Two different mouse models of skin allografts were used: the isotransplant group (C57BL/6--C57BL/6, n=45) and the allotransplantation group (BALB/c--C57BL/6, n=45). The level of IL 16 in sera and skin graft homogenates was tested by ELISA at 1, 3, 5 and 7 days after transplantation and the expression of IL-16 mRNA in skin allografts was measured by reverse transcription PCR at the same time points. RESULTS: At 3, 5 and 7 days after skin transplantation, the levels of IL-16 protein and mRNA in the skin allografts and serum level of IL-16 in the allotransplantation group were significantly higher than those in the isotransplant group. CONCLUSION: The expression of IL-16 is increased in the mouse skin allografts. PMID- 26359105 TI - [IL-33 enhances cytokine secretion and killing function of peripheral blood mononuclear cells in vitro]. AB - OBJECTIVE: To investigate whether interleukin 33 (IL-33) can enhance cytokine secretion and killing activity of peripheral blood mononuclear cells (PBMCs) in vitro. METHODS: PBMCs were harvested from healthy volunteers and stimulated with different combination of cytokines (CD3 mAb/CD28 mAb/IL-2, CD3 mAb/CD28 mAb/IL 2/IL-12, CD3 mAb/CD28 mAb/IL-2/IL-12/IL-33) in vitro. The cells of each group were collected after 72 hours. Total RNA were extracted and assayed by real-time quantitative PCR (qRT-PCR) for the levels of interferon gamma (IFN-gamma) and granzyme B. The cytotoxic activity of the cells targeting A549 human lung adenocarcinoma cells was detected by CCK-8 assay. The levels of programmed death 1 (PD-1) and IFN-gamma were determined by flow cytometry. RESULTS: There was no significant difference in cell morphology observed by microscope among the three groups. In the cells stimulated in the presence of IL-33, the levels of IFN-gamma and granzyme B mRNAs were significantly elevated, cell killing ability was strengthened, and the level of IFN-gamma increased significantly, PD-1 level decreased when compared with the other two groups. CONCLUSION: IL-33 might enhance the function of PBMCs and then promote adaptive anti-tumor immune response. PMID- 26359106 TI - [Expression and clinical significance of PTPN14 in cholangiocarcinoma]. AB - OBJECTIVE: To investigate the expression level of protein tyrosine phosphatase non-receptor type 14 (PTPN14), and analyze the relationship between PTPN14 and clinical pathological features and prognosis of patients with cholangiocarcinoma. METHODS: Expression of PTPN14 protein was detected by immunohistochemistry (IHC) in 57 cholangiocarcinoma tissues and corresponding adjacent normal tissues. The relationship between PTPN14 protein level and the clinical-pathological features of cholangiocarcinoma was analyzed using IBM SPSS 20.0 statistical software. The relationship between PTPN14 protein expression and 5-year overall survival of cholangiocarcinoma patients was investigated by survival curves. RESULTS: IHC revealed that positive rates of PTPN14 protein were 49.1% and 75.4% in cholangiocarcinoma tissues and adjacent tissues, respectively. The expression of PTPN14 protein was significantly associated with TNM I, II, and differentiation degree of cholangiocarcinoma patients, but not significantly associated with age and gender of cholangiocarcinoma patients. The 5-year overall survival rate was higher in the PTPN14-positive patients than the PTPN14-negative ones. CONCLUSION: PTPN14 was down-regulated in cholangiocarcinoma, and negatively correlated with better clinical-pathological features and 5-year overall survival rate of cholangiocarcinoma. PMID- 26359107 TI - [In vitro differentiation of human umbilical cord blood mononuclear cells into mature mast cells induced by cytokines]. AB - OBJECTIVE: To isolate and induce human umbilical cord blood mononuclear cells to differentiate into mature mast cells of high purity. METHODS: Human umbilical cord blood mononuclear cells were differentiated into mature mast cells by the treatment of recombinant human stem cell factor (rhSCF) and recombinant human interleukin 6 (rhIL-6). The cultured cells at different time points were stained with toluidine blue for the detection of anti-FcepsilonRI and the maturity of mast cells was detected by flow cytometry. After the mature mast cells were stimulated with allergen, the levels of histamine and tryptase in the supernatant were determined. RESULTS: The cells started to express FcepsilonRI receptor after 2-week treatment of rhSCF and rhIL-6. After 3 weeks, the amount of FcepsilonRI receptor reached its peak accompanied by increased intracellular basophilic granules. The mature mast cells released tryptase and histamine effectively after allergen challenge. CONCLUSION: Human umbilical cord blood mononuclear cells can be differentiated into mature mast cells by the treatment of rhSCF and rhIL-6. The mature mast cells may be used for the study of allergenicity in vitro. PMID- 26359108 TI - [Preparation of a uncoordinated-5 homolog B monoclonal antibody and its effect on melanoma cell migration in vitro]. AB - OBJECTIVE: To prepare and characterize the monoclonal antibody (mAb) against uncoordinated-5 homolog B (UNC5B) and analyze its effect on the migration of melanoma cells. METHODS: UNC5B gene fragment was cloned into the prokaryotic expression vector pET-32a. The recombinant UNC5B protein was expressed in E.coli BL21 (DE3) and purified by affinity chromatography. BALB/c mice were immunized with the recombinant protein and the hybridoma cell clones stably secreting UNC5B antibody were screened by traditional hybridoma technique. ELISA, Western blotting and flow cytometry were used to characterize the specificity of the antibodies. In addition, the effect of the mAb on melanoma cell migration was analyzed by wound healing assay. RESULTS: The recombinant UNC5B protein was expressed and purified. One high-titer antibody 2C9 was obtained. ELISA, Western blotting and flow cytometry all demonstrated that 2C9 antibody specifically recognized the UNC5B protein. Wound healing assay indicated that the UNC5B mAb could promote melanoma cell migration at the presence of netrin-1. CONCLUSION: A UNC5B-specific monoclonal antibody was prepared and proved to have the ability of promoting melanoma cell migration at the presence of netrin-1. PMID- 26359109 TI - [Preparation and application of polyclonal antibody against amelotin polypeptide]. AB - OBJECTIVE: To prepare and identify the rabbit anti-mouse polyclonal antibody against amelotin polypeptide. METHODS: The polypeptide was synthesized based on the bioinformatics analysis of amelotin, and coupled with keyhole limpet hemocyanin (KLH) for immunization. The amelotin polypeptide-KLH was injected into New Zealand rabbits to prepare the polyclonal antibody. ELISA technology was used to detect the titer of the antibody. The specificity of the polyclonal antibody was identified by Western blotting. The expression of amelotin in the submandibular tissue of mice was observed by immunohistochemistry. RESULTS: ELISA showed that the titer of amelotin antibody was 1:1,000,000. Western blotting verified that the antibody had a high specificity. Immunohistochemistry indicated that amelotin was highly expressed in odontoprisis full-thick enamel of 3-day-old and 7-day-old mice, and also expressed in duct epithelial cytoplasm of submandibular glands of 7-day-old mice. CONCLUSION: The polyclonal antibody against amelotin polypeptide has been prepared successfully with high titer and high specificity. PMID- 26359111 TI - Viral bioterrorism: Learning the lesson of Ebola virus in West Africa 2013-2015. AB - Among the potential biological agents suitable as a weapon, Ebola virus represents a major concern. Classified by the CDC as a category A biological agent, Ebola virus causes severe hemorrhagic fever, characterized by high case fatality rate; to date, no vaccine or approved therapy is available. The EVD epidemic, which broke out in West Africa since the late 2013, has got the issue of the possible use of Ebola virus as biological warfare agent (BWA) to come to the fore once again. In fact, due to its high case-fatality rate, population currently associates this pathogen to a real and tangible threat. Therefore, its use as biological agent by terrorist groups with offensive purpose could have serious repercussions from a psychosocial point of view as well as on closely sanitary level. In this paper, after an initial study of the main characteristics of Ebola virus, its potential as a BWA was evaluated. Furthermore, given the spread of the epidemic in West Africa in 2014 and 2015, the potential dissemination of the virus from an urban setting was evaluated. Finally, it was considered the actual possibility to use this agent as BWA in different scenarios, and the potential effects on one or more nation's stability. PMID- 26359110 TI - Complex genome evolution in Anopheles coluzzii associated with increased insecticide usage in Mali. AB - In certain cases, a species may have access to important genetic variation present in a related species via adaptive introgression. These novel alleles may interact with their new genetic background, resulting in unexpected phenotypes. In this study, we describe a selective sweep on standing variation on the X chromosome in the mosquito Anopheles coluzzii, a principal malaria vector in West Africa. This event may have been influenced by the recent adaptive introgression of the insecticide resistance gene known as kdr from the sister species Anopheles gambiae. Individuals carrying both kdr and a nearly fixed X-linked haplotype, encompassing at least four genes including the P450 gene CYP9K1 and the cuticular protein CPR125, have rapidly increased in relative frequency. In parallel, a reproductively isolated insecticide-susceptible A. gambiae population (Bamako form) has been driven to local extinction, likely due to strong selection from increased insecticide-treated bed net usage. PMID- 26359112 TI - Ultrafast Structural Fluctuations of Myoglobin-Bound Thiocyanate and Selenocyanate Ions Measured with Two-Dimensional Infrared Photon Echo Spectroscopy. AB - Structural dynamics within the distal cavity of myoglobin protein is investigated using 2D-IR and IR pump-probe spectroscopy of the N=C stretch modes of heme-bound thiocyanate and selenocyanate ions. Although myoglobin-bound thiocyanate group shows a doublet in its IR absorption spectrum, no cross peaks originating from chemical exchange between the two components are observed in the time-resolved 2D IR spectra within the experimental time window. Frequency-frequency correlation functions of the two studied anionic ligands are obtained by means of a few different analysis approaches; these functions were then used to elucidate the differences in structural fluctuation around ligand, ligand-protein interactions, and the degree of structural heterogeneity within the hydrophobic pocket of these myoglobin complexes. PMID- 26359113 TI - A Neurocomputational Account of How Inflammation Enhances Sensitivity to Punishments Versus Rewards. AB - BACKGROUND: Inflammation rapidly impairs mood and cognition and, when severe, can appear indistinguishable from major depression. These sickness responses are characterized by an acute reorientation of motivational state; pleasurable activities are avoided, and sensitivity to negative stimuli is enhanced. However, it remains unclear how these rapid shifts in behavior are mediated within the brain. METHODS: Here, we combined computational modeling of choice behavior, experimentally induced inflammation, and functional brain imaging (functional magnetic resonance imaging) to describe these mechanisms. Using a double-blind, randomized crossover study design, 24 healthy volunteers completed a probabilistic instrumental learning task on two separate occasions, one 3 hours after typhoid vaccination and one 3 hours after saline (placebo) injection. Participants learned to select high probability reward (win L1) and avoid high probability punishment (lose L1) stimuli. An action-value learning algorithm was fit to the observed behavior, then used within functional magnetic resonance imaging analyses to identify neural coding of prediction error signals driving motivational learning. RESULTS: Inflammation acutely biased behavior, enhancing punishment compared with reward sensitivity, through distinct actions on neural representations of reward and punishment prediction errors within the ventral striatum and anterior insula. Consequently, choice options leading to potential rewards were less behaviorally attractive, and those leading to punishments were more aversive. CONCLUSIONS: Our findings demonstrate the neural mediation of a rapid, state-dependent reorientation of reward versus punishment sensitivity during inflammation. This mechanism may aid the adaptive reallocation of metabolic resources during acute sickness but might also account for maladaptive, motivational changes that underpin the association between chronic inflammation and depression. PMID- 26359114 TI - Interaction of HSP20 with a viral RdRp changes its sub-cellular localization and distribution pattern in plants. AB - Small heat shock proteins (sHSPs) perform a fundamental role in protecting cells against a wide array of stresses but their biological function during viral infection remains unknown. Rice stripe virus (RSV) causes a severe disease of rice in Eastern Asia. OsHSP20 and its homologue (NbHSP20) were used as baits in yeast two-hybrid (YTH) assays to screen an RSV cDNA library and were found to interact with the viral RNA-dependent RNA polymerase (RdRp) of RSV. Interactions were confirmed by pull-down and BiFC assays. Further analysis showed that the N terminus (residues 1-296) of the RdRp was crucial for the interaction between the HSP20s and viral RdRp and responsible for the alteration of the sub-cellular localization and distribution pattern of HSP20s in protoplasts of rice and epidermal cells of Nicotiana benthamiana. This is the first report that a plant virus or a viral protein alters the expression pattern or sub-cellular distribution of sHSPs. PMID- 26359115 TI - Was the extreme and wide-spread marine oil-snow sedimentation and flocculent accumulation (MOSSFA) event during the Deepwater Horizon blow-out unique? AB - During the Deepwater Horizon blowout, thick layers of oiled material were deposited on the deep seafloor. This large scale benthic concentration of oil is suggested to have occurred via the process of Marine Oil Snow Sedimentation and Flocculent Accumulation (MOSSFA). This meta-analysis investigates whether MOSSFA occurred in other large oil spills and identifies the main drivers of oil sedimentation. MOSSFA was found to have occurred during the IXTOC I blowout and possibly during the Santa Barbara blowout. Unfortunately, benthic effects were not sufficiently studied for the 52 spills we reviewed. However, based on the current understanding of drivers involved, we conclude that MOSSFA and related benthic contamination may be widespread. We suggest to collect and analyze sediment cores at specific spill locations, as improved understanding of the MOSSFA process will allow better informed spill responses in the future, taking into account possible massive oil sedimentation and smothering of (deep) benthic ecosystems. PMID- 26359116 TI - Relationship between the lability of sediment-bound Cd and its bioaccumulation in edible oyster. AB - A linkage between Cd speciation in sediments and its bioaccumulation in edible oyster (Crassostrea sp.) from a tropical estuarine system was established. Bioaccumulation of Cd in edible oyster increased with the increasing lability and dissociation rate constants of Cd-sediment complexes in the bottom sediments. Total Cd concentration in sediment was not a good indicator of Cd bioavailability. Increasing trace metal competition in sediments increased lability and bioavailability of Cd in the tropical estuarine sediment. Low thermodynamic stability and high bioavailability of Cd in the estuarine sediment were responsible for high bioaccumulation of Cd in edible oysters (3.2-12.2mgkg( 1)) even though the total concentration of Cd in the bottom sediment was low (0.17-0.49mgkg(-1)). PMID- 26359117 TI - Sulphur-cycling bacteria and ciliated protozoans in a Beggiatoaceae mat covering organically enriched sediments beneath a salmon farm in a southern Chilean fjord. AB - The colourless mat covering organically enriched sediments underlying an intensive salmon farm in Estero Pichicolo, southern Chile, was surveyed by combined 454 PyroTag and conventional Sanger sequencing of 16S/18S ribosomal RNA genes for Bacteria and Eukarya. The mat was dominated by the sulphide-oxidizing bacteria (SOB) Candidatus Isobeggiatoa, Candidatus Parabeggiatoa and Arcobacter. By order of their abundances, sulphate-reducing bacteria (SRB) were represented by diverse deltaproteobacterial Desulfobacteraceae, but also within Desulfobulbaceae, Desulfuromonadaceae and Desulfovibrionaceae. The eukaryotic PyroTags were dominated by polychaetes, copepods and nematodes, however, ciliated protozoans were highly abundant in microscopy observations, and were represented by the genera Condylostoma, Loxophyllum and Peritromus. Finally, the abundant Sulfurimonas/Sulfurovum also suggest the occurrence of zero-valence sulphur oxidation, probably derived from Beggiatoaceae as a result of bacteriovorus infaunal activity or generated as free S(0) by the Arcobacter bacteria. The survey suggests an intense and complex sulphur cycle within the surface of salmon farm impacted sediments. PMID- 26359118 TI - Pollution risk assessment of oil spill accidents in Garorim Bay of Korea. AB - This study presents a model to assess the oil spill risk in Garorim Bay in Korea, where large-scale oil spill accidents frequently occur. The oil spill risk assessment is carried out by using two factors: 1) The impact probability of the oil spill, and 2) the first impact time of the oil that has been spilt. The risk assessment is conducted for environmentally sensitive areas, such as the coastline and aquaculture farms in the Garorim Bay area. Finally, Garorim Bay is divided into six subareas, and the risks of each subarea are compared with one another to identify the subarea that is most vulnerable to an oil spill accident. These results represent an objective and comprehensive oil spill risk level for a specific region. The prediction of the oil spill spread is based on real-time sea conditions and can be improved by integrating our results, especially when sea conditions are rapidly changing. PMID- 26359119 TI - Comparative Efficacy of Cardiac Resynchronization Therapy in Africans Americans Compared With European Americans. AB - Race has seldomly been reported in the major clinical trials of cardiac resynchronization therapy (CRT). When described, African Americans (AAs) were substantially under-represented. This study sought to compare reverse ventricular remodeling and long-term outcomes in AAs versus European Americans (EAs) with advanced heart failure who underwent CRT. We extracted demographic (including race), clinical, and echocardiographic data on patients with advanced heart failure who underwent CRT with a left ventricular ejection fraction (LVEF) <=35% and a QRS duration >=120 ms. Long-term outcomes were compared between AAs and EAs. In patients in whom follow-up echocardiograms were available, improvement in LVEF (defined as an absolute improvement >=5%) was compared between races. From a cohort of 662 patients, there were 88 AAs and 574 EAs. At a mean follow-up of 5.0 +/- 2.5 years, survival rate free of left ventricular assist device (LVAD) and heart transplant was 54.5% for AAs and 53.8% for EAs (log-rank p = 0.997). In multivariate analysis, there was no difference in survival free of heart transplant or LVAD based on race (hazard ratio 1.1 [0.74 to 1.56], p = 0.72, EAs race as referent); 424 patients had a follow-up echocardiogram (55.4% EAs and 64.7% AAs). In multivariate analysis, there was no difference in the incidence of response based on race (1.1 [0.6 to 2.1, p = 0.80], EAs as referent). AAs derive similar benefits with CRT compared with EAs in terms of improvement in LVEF and long-term survival free of LVAD and heart transplant. PMID- 26359120 TI - Hospital-based register of stroke in the Molise Region: focus on main subtypes of stroke. Years 2009-2013. AB - We determined incidence and intra-hospital mortality rate of stroke in Molise, Italy, to provide information for planning regional healthcare facilities and to ameliorate stroke management in this region. This study is part of the "Rete Molisana dell'Ictus Cerebrale (REMOLIC)" study, a population-based Cerebrovascular Registry in Molise, from 2009 to 2013, with a cold pursuit approach. The crude annual incidence rates for total stroke per 100,000 inhabitants, notified by hospital discharge records, were 198 for 2009, 185 for 2010, 169 for 2011, and 176 for both 2012 and 2013. There was a significant decrease in risk in the years 2011-2013 [RR2011 vs. 2009: 0.85 (0.76-0.98), RR2012 vs. 2009: 0.89 (0.79-0.99), RR2013 vs. 2009: 0.89 (0.79-0.99)] as compared with 2009. For the year 2010, after adjustment to the Italian, European, and world populations, the overall incidence rates were 165, 134, and 67 per 100,000/year, respectively. Similar trends were found when men and women were analyzed separately. In the average, 20.8 % of subjects admitted for a cerebrovascular accident died during the hospitalization, among these 93.5 % in the first 28 days. The duration of hospital stay was constant in the years (2009 2012), except during 2013, where there was a significant decrease in the average (p < 0.001). Our study shows incidence rates decreasing from 2009 to 2013, while mortality rates were stable during the same years. This study underlines the need to plan better stroke management in Italy, in order to obtain outcomes more similar to those of the best performing countries. PMID- 26359123 TI - NREM-related parasomnias in Machado-Joseph disease: clinical and polysomnographic evaluation. AB - Spinocerebellar ataxias (SCA) are autosomal dominant neurodegenerative disorders that affect the cerebellum and its connections, and have a marked clinical and genetic variability. Machado-Joseph disease (MJD) or spinocerebellar ataxia type 3 (SCA3)--MJD/SCA3--is the most common SCA worldwide. MJD/SCA3 is characterized classically by progressive ataxia and variable other motor and non-motor symptoms. Sleep disorders are common, and include rapid eye movement (REM) sleep behaviour disorder (RBD), restless legs syndrome (RLS), insomnia, excessive daytime sleepiness, excessive fragmentary myoclonus and sleep apnea. This study aims to focus upon determining the presence or not of non-REM (NREM)-related parasomnias in MJD/SCA 3, using data from polysomnography (PSG) and clinical evaluation. Forty-seven patients with clinical and genetic diagnosis of MJD/SCA3 and 47 control subjects were evaluated clinically and by polysomnography. MJD/SCA3 patients had a higher frequency of arousals from slow wave sleep (P < 0.001), parasomnia complaints (confusional arousal/sleep terrors, P = 0.001; RBD, P < 0.001; and nightmares, P < 0.001), REM sleep without atonia (P < 0.001), periodic limb movements of sleep index (PLMSi) (P < 0.001), percentage of N3 sleep (P < 0.001) and percentage of N1 sleep (P < 0.001). These data show that NREM-related parasomnias must be included in the spectrum of sleep disorders in MJD/SCA3 patients. PMID- 26359122 TI - Low visual cortex GABA levels in hepatic encephalopathy: links to blood ammonia, critical flicker frequency, and brain osmolytes. AB - The pathogenesis of hepatic encephalopathy (HE) is not fully understood yet. Hyperammonemia due to liver failure and subsequent disturbance of cerebral osmolytic balance is thought to play a pivotal role in the emergence of HE. The aim of this in-vivo MR spectroscopy study was to investigate the levels of gamma aminobutyric acid (GABA) and its correlations with clinical symptoms of HE, blood ammonia, critical flicker frequency, and osmolytic levels. Thirty patients with minimal HE or HE1 and 16 age-matched healthy controls underwent graduation of HE according to the West-Haven criteria and including the critical flicker frequency (CFF), neuropsychometric testing and blood testing. Edited proton magnetic resonance spectroscopy ((1)H MRS) was used to non-invasively measure the concentrations of GABA, glutamate (Glu), glutamine (Gln), and myo-inositol (mI) - all normalized to creatine (Cr) - in visual and sensorimotor cortex. GABA/Cr in the visual area was significantly decreased in mHE and HE1 patients and correlated both to the CFF (r = 0.401, P = 0.013) and blood ammonia levels (r = 0.434, P = 0.006). Visual GABA/Cr was also strongly linked to mI/Cr (r = 0.720, P < 0.001) and Gln/Cr (r = -0.699, P < 0.001). No group differences or correlations were found for GABA/Cr in the sensorimotor area. Hepatic encephalopathy is associated with a regional specific decrease of GABA levels in the visual cortex, while no changes were revealed for the sensorimotor cortex. Correlations of visual GABA/Cr with CFF, blood ammonia, and osmolytic regulators mI and Gln indicate that decreased visual GABA levels might contribute to HE symptoms, most likely as a consequence of hyperammonemia. PMID- 26359121 TI - Inflammatory and metabolic markers and short-time outcome in patients with acute ischemic stroke in relation to TOAST subtypes. AB - The aim of this study was to evaluate the association between inflammatory and metabolic markers and short-time outcome with acute ischemic stroke subtypes. A total of 121 patients was classified according to TOAST criteria, such as large artery atherosclerosis (LAAS), lacunar infarct (LAC), cardioembolic infarct (CEI), other determined etiology (ODE), and undetermined etiology (UDE). The functional impairment was evaluated within the first eight hours of stroke and the outcome after three-month follow-up using the modified Rankin Scale. Blood samples were obtained up to 24 h of stroke. Compared with 96 controls, patients with LAAS, CEI, and LAC subtypes showed higher levels of white blood cells, high sensitivity C-reactive protein (hsCRP), interleukin 6 (IL-6), metalloproteinase 9 (MMP-9), glucose, and iron (p < 0.05); and lower high-density lipoprotein cholesterol (HDL-C) (p < 0.0001); platelets, insulin, insulin resistance, and homocysteine were higher in LAC (p < 0.0001); ferritin was higher in LAAS (p < 0.0001); and total cholesterol (TC) was lower in LAAS and CEI (p < 0.01). When stroke subtypes were compared, insulin was higher in LAAS vs. LAC and in LAC vs. CEI (p < 0.05); and TC was lower in LAAS vs. LAC (p < 0.05). Outcome and rate of mortality after three-month were higher in LAAS vs. LAC (p < 0.001 and p = 0.0391 respectively). The results underscored the important role of the inflammatory response and metabolic changes in the pathogenesis of ischemic stroke subtypes that might be considered on the initial evaluation of stroke patients to identify those that could benefit with individualized therapeutic strategies that taken into account these markers after acute ischemic event. PMID- 26359125 TI - Polymeric nanoparticles and microparticles for the delivery of peptides, biologics, and soluble therapeutics. AB - Biologically derived therapeutics, or biologics, are the most rapidly growing segment of the pharmaceutical marketplace. However, there are still unmet needs in improving the delivery of biologics. Injectable polymeric nanoparticles and microparticles capable of releasing proteins and peptides over time periods as long as weeks or months have been a major focus in the effort to decrease the frequency of administration. These particle systems fit broadly into two categories: those composed of hydrophilic and those composed of hydrophobic polymeric scaffolds. Here we review the factors that contribute to the slow and controlled release from each class of particle, as well as the effects of synthesis parameters and product design on the loading, encapsulation efficiency, biologic integrity, and release profile. Generally, hydrophilic scaffolds are ideal for large proteins while hydrophobic scaffolds are more appropriate for smaller biologics without secondary structure. Here we also introduce a Flash NanoPrecipitation method that has been adopted for encapsulating biologics in nanoparticles (40-200nm) at high loadings (50-75wt.%) and high encapsulation efficiencies. The hydrophilic gel interior and hydrophobic shell provide an opportunity to combine the best of both classes of injectable polymeric depots. PMID- 26359124 TI - Diaminosulfide based polymer microparticles as cancer vaccine delivery systems. AB - The aim of the research presented here was to determine the characteristics and immunostimulatory capacity, in vivo, of antigen and adjuvant co-loaded into microparticles made from a novel diaminosulfide polymer, poly(4,4' trimethylenedipiperdyl sulfide) (PNSN), and to assess their potential as cancer vaccine vectors. PNSN microparticles co-loaded with the antigen, ovalbumin (OVA), and adjuvant, CpG 1826, (PNSN(OVA + CpG)) were fabricated and characterized for size (1.64 MUm diameter; PDI=0.62), charge (-23.1 +/- 0.3), and loading efficiencies of antigen (7.32 MUg/mg particles) and adjuvant (0.95 MUg/mg particles). The ability of PNSN(OVA + CpG) to stimulate cellular and humoral immune responses in vivo was compared with other PNSN microparticle formulations as well as with poly(lactic-co-glycolic acid)(PLGA)-based microparticles, co loaded with OVA and CpG (PLGA(OVA + CpG)), an adenovirus encoding OVA (Ad5-OVA), and OVA delivered with incomplete Freund's adjuvant (IFA(OVA)). In vivo OVA specific IgG1 responses, after subcutaneous prime/boosts in mice, were similar when PNSN(OVA + CpG) and PLGA(OVA + CpG) were compared and the presence of CpG 1826 within the PNSN microparticles demonstrated significantly improved responses when compared to PNSN microparticles loaded with OVA alone (PNSN(OVA)), plus or minus soluble CpG 1826. Cellular immune responses to all particle-based vaccine formulations ranged from being negligible to modest with PNSN(OVA + CpG) generating the greatest responses, displaying significantly increased levels of OVA-specific CD8+ T lymphocytes compared to controls and IFA(OVA) treated mice. Finally, it was shown that of all vaccination formulations tested PNSN(OVA + CpG) was the most protective against subsequent challenge with an OVA-expressing tumor cell line, E.G7. Thus, microparticles made from poly(diaminosulfide)-based macromolecules possess promising potential as vaccine vectors and, as demonstrated here, may have impact as cancer vaccines in particular. PMID- 26359126 TI - Treatment duration and factors associated with the surgery-first approach: a two center study. AB - BACKGROUND: The aim of this study was to evaluate treatment duration and number of appointments in orthognathic surgery using the surgery-first approach (SFA) and to evaluate the factors associated to these outcomes. METHODS: This was a retrospective chart review of consecutively treated patients with SFA at a University clinic and a private practice setting. Treatment duration, number of appointment, and factors associated to this duration such as patient demographics, type of surgery, use of 3D planning, and treatment center among others were evaluated. Multivariable linear regression models were used to examine the simultaneous association between all predictor variables and outcomes. RESULTS: Median treatment duration for patients undergoing SFA was 9.6 months [6.1 (25 % percentile); 13.4 (75 % percentile)] with a median number of 13.8 appointments [9 (25 % percentile); 17 (75 % percentile)]. Transverse maxillary expansion was associated with longer treatment duration and number of appointments. There was also a significant difference in number of appointments between the two treatment centers. CONCLUSIONS: SFA significantly reduces treatment duration in orthognathic surgery. Transverse expansion is associated with longer treatment duration and number of appointments. PMID- 26359127 TI - Methodological Perspectives from 'Milrinone for the Treatment of Acute Heart Failure After Acute Myocardial Infarction: A Systematic Review and Meta analysis'. PMID- 26359128 TI - Sleep and the generalization of fear learning. AB - Fear conditioning is an important survival mechanism, as is the ability to generalize learned fear responses to stimuli that are similar to the original conditioned stimulus. Overgeneralization of fear learning, prominent in many anxiety disorders, is however highly maladaptive. Because sleep is involved in the consolidation of fear learning, and in active processing of information, the present study explored the effect of sleep on generalization of fear learning. Participants watched a random sequence of pictures of a small and a big circle, one of them coupled with an aversive sound. Then, after a delay period containing either a nap or wake, generalization was examined as participants watched the two circles again, together with eight novel circles that gradually varied in size between the former two. Results showed that the fear response increased as a function of similarity to the conditioned response. However, there was no difference in the degree of generalization between the sleep and the wake group. PMID- 26359129 TI - Asymmetric linkage disequilibrium: Tools for assessing multiallelic LD. AB - Standard measures of linkage disequilibrium (LD) provide an incomplete description of the correlation between two loci. Recently, Thomson and Single (2014) described a new asymmetric pair of LD measures (ALD) that give a more complete description of LD. The ALD measures are symmetric and equivalent to the correlation coefficient r when both loci are bi-allelic. When the numbers of alleles at the two loci differ, the ALD measures capture this asymmetry and provide additional detail about the LD structure. In disease association studies the ALD measures are useful for identifying additional disease genes in a genetic region, by conditioning on known effects. In evolutionary genetic studies ALD measures provide insight into selection acting on individual amino acids of specific genes, or other loci in high LD (see Thomson and Single (2014) for these examples). Here we describe new software for computing and visualizing ALD. We demonstrate the utility of this software using haplotype frequency data from the National Marrow Donor Program (NMDP). This enhances our understanding of LD patterns in the NMDP data by quantifying the degree to which LD is asymmetric and also quantifies this effect for individual alleles. PMID- 26359130 TI - Survey of the incidence of pectinate ligament dysplasia and glaucoma in the UK Leonberger population. AB - OBJECTIVE: To determine the prevalence of pectinate ligament dysplasia (PLD) in UK Leonbergers and identify cases affected by glaucoma. Also, to define the spectrum of pectinate ligament (PL) appearance in this breed and determine whether gonioscopic monitoring should be recommended. ANIMALS STUDIED: Data were compiled from 78 prospective gonioscopy examinations performed by one author (GF) and retrospective analysis of 233 UK eye scheme certificates (2009-2014). Clinical cases of glaucoma in Leonbergers diagnosed by UK veterinary ophthalmologists, where gonioscopy of the fellow eyes or histology of affected eyes had been performed, were also reviewed. PROCEDURE: In the prospective study, intraocular pressure was recorded prior to gonioscopy using a rebound tonometer. Gonioscopy was performed using a slit-lamp biomicroscope with a Koeppe goniolens. PLD was categorized according to the percentage of the iridocorneal drainage angle affected (grade 0 = <25% affected; grade 1 = 25-50% affected; grade 2 = 51 75% affected; and grade 3 = >75% affected), and the degree of narrowing of the angle was noted. RESULTS: Of 78 dogs examined prospectively, 64/78 (82%) were grade 0, 7/78 (9%) were grade 1, 3/78 (4%) were grade 2, and 4/78 (5%) were grade 3. A large phenotypic variation was observed. Spearman's rank correlation showed a positive correlation between age and severity of PLD (P < 0.0055). 52 (22%) of Leonbergers examined under the UK eye scheme 2009-2014 were affected by PLD. Five clinical cases of glaucoma were reviewed where gonioscopy had been performed and one where histology was performed. All individuals had grade 3 PLD with gonioscopy of the contralateral eye or severe goniodysgenesis with histological sections of the affected eye. CONCLUSION: This survey suggests the prevalence of PLD is sufficient to justify ongoing screening of Leonbergers. PMID- 26359132 TI - Your advice to new medical students. PMID- 26359131 TI - Identification of regions of normal grey matter and white matter from pathologic glioblastoma and necrosis in frozen sections using Raman imaging. AB - In neurosurgical applications, a tool capable of distinguishing grey matter, white matter, and areas of tumor and/or necrosis in near-real time could greatly aid in tumor resection decision making. Raman spectroscopy is a non-destructive spectroscopic technique which provides molecular information about the tissue under examination based on the vibrational properties of the constituent molecules. With careful measurement and data processing, a spatial step and repeat acquisition of Raman spectra can be used to create Raman images. Forty frozen brain tissue sections were imaged in their entirety using a 300-um-square measurement grid, and two or more regions of interest within each tissue were also imaged using a 25 um-square step size. Molecular correlates for histologic features of interest were identified within the Raman spectra, and novel imaging algorithms were developed to compare molecular features across multiple tissues. In previous work, the relative concentration of individual biomolecules was imaged. Here, the relative concentrations of 1004, 1300:1344, and 1660 cm(-1), which correspond primarily to protein and lipid content, were simultaneously imaged across all tissues. This provided simple interpretation of boundaries between grey matter, white matter, and diseased tissue, and corresponded with findings from adjacent hematoxylin and eosin-stained sections. This novel, yet simple, multi-channel imaging technique allows clinically-relevant resolution with straightforward molecular interpretation of Raman images not possible by imaging any single peak. This method can be applied to either surgical or laboratory tools for rapid, non-destructive imaging of grey and white matter. PMID- 26359133 TI - 'Catch it early, save a life and save a breast': this misleading mantra of mammography. PMID- 26359134 TI - Medical administrators - physician superintendent. PMID- 26359135 TI - Mammography screening is harmful and should be abandoned. PMID- 26359137 TI - The 1959 meeting in Vienna on controlled clinical trials - A methodological landmark. PMID- 26359136 TI - From alga to omega; have we reached peak (fish) oil? AB - SummaryWhile the Inuit diet was highly cardio-protective and consuming oily fish within a Western diet is to a lesser degree, the case for purified fish oil supplements is less convincing. Purification of fish oil removes lipophilic polyphenols which likely contribute to the health benefits of oily fish; leaving the omega3 highly unsaturated fatty acids exposed and prone to conferring oxidative and inflammatory stress. The authors believe that due to such issues as dietary shift, it may now be inadvisable to prescribe or sell purified omega3 highly unsaturated fatty acids supplements, unless the appropriate co-factors are included. PMID- 26359141 TI - Toxicological evaluation of isopropylparaben and isobutylparaben mixture in Sprague-Dawley rats following 28 days of dermal exposure. AB - The alkyl esters of p-hydroxybenzoic acid (Parabens) have been of concern due to their probable endocrine disrupting property especially in baby consumer products. The safety of parabens for use as a preservative in cosmetics has come into controversy, and thus consumer demand for paraben-free products is ever increasing. Thus, more comprehensive studies are needed to conclusively determine the safety of the multiple prolonged exposure to parabens with cosmetic ingredients. This study was conducted to investigate the potential repeated 28 days dermal toxicity (50, 100, 300, or 600 mg/kg bw/day) of isopropylparaben (IPP), isobutylparaben (IBP), or the mixture of IPP and IBP in rats. There were no significant changes in body and organ weights in any group. However, histopathological examinations showed that weak or moderate skin damages were observed in female rats by macroscopic and microscopic evaluations. In female rats, no observed adverse effect levels (NOAELs) of IPP with no skin lesion and IBP for skin hyperkeratosis, were estimated to be 600 mg/kg bw/day, and 50 mg/kg bw/day, respectively. With regard skin hyperkeratosis, the lowest observed adverse effect level (LOAEL) of the mixture of IPP and IBP was estimated to be 50 mg/kg bw/day. Analysis of six serum hormones (estrogen, testosterone, insulin, T3, TSH, or FSH) in animals showed that only FSH was dose-dependently decreased in the mixture groups of 100 mg/kg bw/day or higher. These data suggest that the mixture of IPP and IBP showed a synergistic dermal toxicity in rats and should be considered for future use in consumer products. PMID- 26359142 TI - Corneal and anterior segment foreign body trauma in dogs: a review of 218 cases. AB - OBJECTIVES: To review clinical data on dogs that suffered a corneal and anterior segment foreign body (CASFB) trauma and to determine the risk factors for foreign body (FB) trauma and subsequent enucleation. ANIMALS STUDIED: Dogs with CASFB presented to the Animal Health Trust (AHT) from January 2000 to December 2012. PROCEDURES: Clinical data for CASFB cases were compared to those available for the remaining AHT ophthalmic population over the same period. The depth of the FB trauma was divided into five categories. The type of FB and method of removal were described for each category. The degree of secondary uveitis and lens involvement was graded and correlated with subsequent enucleation. RESULTS: The mean age (standard deviation) of 218 identified CASFB cases was 3.96 (2.95) years. Risk factors for CASFB trauma were dogs younger than 5 years, English Springer Spaniels, Labrador Retrievers, and working dogs. Most dogs required general anesthesia for FB removal, and hypodermic needles were the most commonly used instrument. The lens was involved in some cases with a full-thickness CASFB trauma (n = 49, 45%), but most suffered a minor lens trauma (n = 37, 76%). The lens trauma and phacoclastic uveitis were managed medically in most dogs (n = 37, 76%), and phacoemulsification was only elected as initial treatment in some dogs (n = 10, 20%). Enucleation was required overall in 6% of dogs. Statistically significant associations were found between enucleation and depth of FB trauma, degree of uveitis, and severity of lens trauma (P < 0.001). CONCLUSIONS: Young dogs, English Springer Spaniels, Labrador Retrievers, and working dogs had an increased risk of CASFB trauma. Risk factors for enucleation were full-thickness FB penetration, severe lens trauma, and severe uveitis. PMID- 26359143 TI - Assessment of serum adiponectin in Egyptian patients with HCV-related cirrhosis and hepatocellular carcinoma. AB - BACKGROUND AND AIM: Hepatitis C-associated insulin resistance is involved in the development of various complications including hepatocarcinogenesis. Low plasma levels of adiponectin contribute to the pathogenesis of insulin resistance and type II diabetes mellitus. The aim of this study was to determine the value of serum adiponectin in Egyptian patients with hepatitis C-related cirrhosis and hepatocellular carcinoma. PATIENTS AND METHODS: 90 Egyptian patients with hepatitis C-related liver cirrhosis were enrolled in this study. Patients were divided into two groups as follows: group I: 61 patients with hepatitis C-related cirrhosis and hepatocellular carcinoma, group II: 29 patients with hepatitis C related cirrhosis (hepatocellular carcinoma was excluded in these patients at the time of recruitment in the study). Serum adiponectin level was measured and correlated with all other studied parameters. RESULTS: Serum adiponectin was significantly lower in patients with hepatocellular carcinoma and it had significant negative correlations with both the overall tumor size and the number of tumor foci. Highly significant negative correlations were found between adiponectin and all markers of insulin resistance in both groups. At a cut-off value <=5.4 MUg/ml, adiponectin had a sensitivity of 60.7%, a specificity of 93.1%, a positive predictive value of 94.9%, and a negative predictive value of 52.9% for detection of hepatocellular carcinoma (with an overall accuracy of 77.6%). CONCLUSION: An independent association exists between serum adiponectin and hepatocellular carcinoma in Egyptian patients with hepatitis C-related cirrhosis. Therapy to increase circulating adiponectin concentration might represent a novel strategy to prevent hepatitis C-related hepatic complications. PMID- 26359144 TI - A reappraisal of vitamin D effect on non-skeletal targets and mortality. PMID- 26359146 TI - Standardized Brain Tumor Imaging Protocol for Clinical Trials. PMID- 26359145 TI - Socioeconomic status and prevalence of self-reported diabetes among adults in Tehran: results from a large population-based cross-sectional study (Urban HEART 2). AB - INTRODUCTION: Diabetes mellitus is an important public health challenge worldwide. The prevalence of type 2 diabetes varies across countries. The aim of this study is to estimate the prevalence of type 2 diabetes and to determine related factors including socioeconomic factors in a large random sample of Tehran population in 2011. METHODS: In this cross-sectional study, 91,814 individuals aged over 20 years were selected randomly based on a multistage, cluster sampling. All participants were interviewed by trained personnel using standard questionnaires. Prevalence and Townsend deprivation indexes were calculated. Principal component analysis (PCA) was used to construct wealth index. Logistic regression model was used in multivariate analysis. RESULTS: The estimated prevalence of self-reported diabetes was 4.98 % overall, 4.76 %in men and 5.19 % in women (P < 0.003). In multivariate analysis, age, marital status (married and divorced/widow) and BMI were positively associated with the prevalence of self-reported diabetes. Of the socioeconomic variables, educational level and wealth status were negatively and Townsend Index was positively associated with diabetes. CONCLUSION: Our study findings highlight low reported prevalence of diabetes among adults in Tehran. Subjects with low socioeconomic status (SES) had a higher prevalence of type 2 diabetes. Weight gain and obesity were the most important risk factors associated with type 2 diabetes. Wealth index and educational level were better socioeconomic indicators for presenting the inequality in diabetes prevalence in relation to Townsend deprivation index. PMID- 26359147 TI - MRI Texture Analysis Reveals Bulbar Abnormalities in Friedreich Ataxia. AB - BACKGROUND AND PURPOSE: Texture analysis is an image processing technique that can be used to extract parameters able to describe meaningful features of an image or ROI. Texture analysis based on the gray level co-occurrence matrix gives a second-order statistical description of the image or ROI. In this work, the co occurrence matrix texture approach was used to extract information from brain MR images of patients with Friedreich ataxia and a control group, to see whether texture parameters were different between these groups. A longitudinal analysis was also performed. MATERIALS AND METHODS: Twenty patients and 21 healthy controls participated in the study. Both groups had 2 sets of T1-weighted MR images obtained 1 year apart for every subject. ROIs chosen for analysis were the medulla oblongata and pons. Texture parameters were obtained for these ROIs for every subject, for the 2 sets of images. These parameters were compared longitudinally within groups and transversally between groups. RESULTS: The comparison between patients and the control group showed a significant differences for the medulla oblongata (t test, P < .05, Bonferroni-corrected) but did not show a statistically significant difference for the pons. Longitudinal comparison of images obtained 1 year apart did not show differences for either patients or for controls, in any of the analyzed structures. CONCLUSIONS: Gray level co-occurrence matrix-based texture analysis showed statistically significant differences for the medulla oblongata of patients with Friedreich ataxia compared with controls. These results highlight the medulla as an important site of damage in Friedreich ataxia. PMID- 26359148 TI - Optimal Diagnostic Indices for Idiopathic Normal Pressure Hydrocephalus Based on the 3D Quantitative Volumetric Analysis for the Cerebral Ventricle and Subarachnoid Space. AB - BACKGROUND AND PURPOSE: Despite the remarkable progress of 3D graphics technology, the Evans index has been the most popular index for ventricular enlargement. We investigated a novel reliable index for the MR imaging features specified in idiopathic normal pressure hydrocephalus, rather than the Evans index. MATERIALS AND METHODS: The patients with suspected idiopathic normal pressure hydrocephalus on the basis of the ventriculomegaly and a triad of symptoms underwent the CSF tap test. CSF volumes were extracted from a T2 weighted 3D spin-echo sequence named "sampling perfection with application optimized contrasts by using different flip angle evolutions (SPACE)" on 3T MR imaging and were quantified semiautomatically. Subarachnoid spaces were divided as follows: upper and lower parts and 4 compartments of frontal convexity, parietal convexity, Sylvian fissure and basal cistern, and posterior fossa. The maximum length of 3 axial directions in the bilateral ventricles and their frontal horns was measured. The "z-Evans Index" was defined as the maximum z axial length of the frontal horns to the maximum cranial z-axial length. These parameters were evaluated for the predictive accuracy for the tap-positive groups compared with the tap-negative groups and age-adjusted odds ratios at the optimal thresholds. RESULTS: In this study, 24 patients with tap-positive idiopathic normal pressure hydrocephalus, 25 patients without response to the tap test, and 23 age-matched controls were included. The frontal horns of the bilateral ventricles were expanded, with the most excessive expansion being toward the z direction. The CSF volume of the parietal convexity had the highest area under the receiver operating characteristic curve (0.768), the z-Evans Index was the second (0.758), and the upper-to-lower subarachnoid space ratio index was the third (0.723), to discriminate the tap-test response. CONCLUSIONS: The CSF volume of the parietal convexity of <38 mL, upper-to-lower subarachnoid space ratio of <0.33, and the z-Evans Index of >0.42 were newly proposed useful indices for the idiopathic normal pressure hydrocephalus diagnosis, an alternative to the Evans Index. PMID- 26359149 TI - Accuracy of 2-Phase Parathyroid CT for the Preoperative Localization of Parathyroid Adenomas in Primary Hyperparathyroidism. AB - BACKGROUND AND PURPOSE: Minimally invasive parathyroidectomy requires accurate preoperative localization of suspected adenomas, and multiphase CT allows adenoma characterization while providing detailed anatomic information. The purpose of this study was to assess the feasibility of a protocol using only arterial and venous phases to localize pathologic glands in patients with primary hyperparathyroidism. MATERIALS AND METHODS: We identified 278 patients with primary hyperparathyroidism who had undergone 2-phase CT with surgical cure. All scans were read prospectively by board-certified neuroradiologists. A neuroradiology fellow retrospectively reviewed images and reports and classified suspected adenomas on the basis of anatomic location. Accuracy was determined by comparing imaging results with surgical findings. The ability of 2-phase CT to localize adenomas to 1 of 4 neck quadrants and lateralize them to the correct side was assessed. Accuracy of identifying multigland disease was also evaluated. RESULTS: In patients with single-gland disease, the sensitivity and specificity of 2-phase CT to correctly localize the quadrant were 55.4% and 85.9%, respectively. The sensitivity and specificity of correct lateralization were 78.8% and 67.8%, respectively. The sensitivity and specificity to identify multigland disease were 22.9% and 79.5%, respectively. CONCLUSIONS: While the 2 phase CT protocol in this study demonstrates lower accuracy compared with reports of other techniques, its lower radiation compared with 3- and 4-phase techniques may make it a feasible alternative for preoperative parathyroid localization. Further prospective studies are needed to identify patients for whom this technique is most suitable. PMID- 26359150 TI - Dynamic 4D MRI for Characterization of Parathyroid Adenomas: Multiparametric Analysis. AB - BACKGROUND AND PURPOSE: The hypervascular nature of parathyroid adenomas can be explored by proper dynamic imaging to narrow the target lesions for surgical exploration. The purpose of this study was to establish MR perfusion characteristics of parathyroid adenomas to differentiate them from their mimics, such as subjacent thyroid tissue and cervical lymph nodes. MATERIALS AND METHODS: Preoperative high-spatial and -temporal resolution dynamic 4D contrast-enhanced MR imaging in 30 patients with surgically proved parathyroid adenomas was evaluated retrospectively. Using coregistered images, we placed ROIs over the parathyroid adenoma, thyroid gland, and a cervical lymph node (jugulodigastric) to obtain peak enhancement, time-to-peak, wash-in, and washout in each patient. Data were analyzed by logistic regression and analysis of variance. Receiver operating characteristic analysis was performed to determine the optimal parameters for determination of parathyroid adenomas versus thyroid tissue and cervical lymph nodes. RESULTS: Parathyroid adenomas showed significantly (P < .05) faster time-to-peak, higher wash-in, and higher washout compared with cervical lymph nodes and significantly (P < .05) higher peak enhancement, faster time-to-peak, higher wash-in, and higher washout compared with thyroid tissue. Logistic regression analysis indicated significant contribution from time-to-peak (P = .02), wash-in (P = .03), and washout (P = .008) for differentiation of parathyroid adenomas from thyroid and cervical lymph nodes. Using receiver operating characteristic analysis, we obtained the best diagnostic accuracy from a combination of time-to-peak/wash-in/washout in the differentiation of parathyroid adenomas versus lymph nodes (area under the curve, 0.96; sensitivity/specificity, 88%/90%) and in distinguishing parathyroid adenomas versus thyroid tissue (area under the curve, 0.96; sensitivity/specificity, 91%/95%). CONCLUSIONS: Dynamic 4D contrast-enhanced MR imaging can be used to exploit the hypervascular nature of parathyroid adenomas. Multiparametric MR perfusion can distinguish parathyroid adenomas from subjacent thyroid tissue or lymph nodes with diagnostic accuracies of 96%. PMID- 26359151 TI - Impact of Software Modeling on the Accuracy of Perfusion MRI in Glioma. AB - BACKGROUND AND PURPOSE: Relative cerebral blood volume, as measured by T2* weighted dynamic susceptibility-weighted contrast-enhanced MRI, represents the most robust and widely used perfusion MR imaging metric in neuro-oncology. Our aim was to determine whether differences in modeling implementation will impact the correction of leakage effects (from blood-brain barrier disruption) and the accuracy of relative CBV calculations as measured on T2*-weighted dynamic susceptibility-weighted contrast-enhanced MR imaging at 3T field strength. MATERIALS AND METHODS: This study included 52 patients with glioma undergoing DSC MR imaging. Thirty-six patients underwent both non-preload dose- and preload dose corrected DSC acquisitions, with 16 patients undergoing preload dose-corrected acquisitions only. For each acquisition, we generated 2 sets of relative CBV metrics by using 2 separate, widely published, FDA-approved commercial software packages: IB Neuro and nordicICE. We calculated 4 relative CBV metrics within tumor volumes: mean relative CBV, mode relative CBV, percentage of voxels with relative CBV > 1.75, and percentage of voxels with relative CBV > 1.0 (fractional tumor burden). We determined Pearson (r) and Spearman (rho) correlations between non-preload dose- and preload dose-corrected metrics. In a subset of patients with recurrent glioblastoma (n = 25), we determined receiver operating characteristic area under the curve for fractional tumor burden accuracy to predict the tissue diagnosis of tumor recurrence versus posttreatment effect. We also determined correlations between rCBV and microvessel area from stereotactic biopsies (n = 29) in 12 patients. RESULTS: With IB Neuro, relative CBV metrics correlated highly between non-preload dose- and preload dose-corrected conditions for fractional tumor burden (r = 0.96, rho = 0.94), percentage > 1.75 (r = 0.93, rho = 0.91), mean (r = 0.87, rho = 0.86), and mode (r = 0.78, rho = 0.76). These correlations dropped substantially with nordicICE. With fractional tumor burden, IB Neuro was more accurate than nordicICE in diagnosing tumor versus posttreatment effect (area under the curve = 0.85 versus 0.67) (P < .01). The highest relative CBV-microvessel area correlations required preload dose and IB Neuro (r = 0.64, rho = 0.58, P = .001). CONCLUSIONS: Different implementations of perfusion MR imaging software modeling can impact the accuracy of leakage correction, relative CBV calculation, and correlations with histologic benchmarks. PMID- 26359152 TI - High-Resolution C-Arm CT and Metal Artifact Reduction Software: A Novel Imaging Modality for Analyzing Aneurysms Treated with Stent-Assisted Coil Embolization. AB - BACKGROUND AND PURPOSE: Combination of high-resolution C-arm CT and novel metal artifact reduction software may contribute to the assessment of aneurysms treated with stent-assisted coil embolization. This study aimed to evaluate the efficacy of a novel Metal Artifact Reduction prototype software combined with the currently available high spatial-resolution C-arm CT prototype implementation by using an experimental aneurysm model treated with stent-assisted coil embolization. MATERIALS AND METHODS: Eight experimental aneurysms were created in 6 swine. Coil embolization of each aneurysm was performed by using a stent assisted technique. High-resolution C-arm CT with intra-arterial contrast injection was performed immediately after the treatment. The obtained images were processed with Metal Artifact Reduction. Five neurointerventional specialists reviewed the image quality before and after Metal Artifact Reduction. Observational and quantitative analyses (via image analysis software) were performed. RESULTS: Every aneurysm was successfully created and treated with stent-assisted coil embolization. Before Metal Artifact Reduction, coil loops protruding through the stent lumen were not visualized due to the prominent metal artifacts produced by the coils. These became visible after Metal Artifact Reduction processing. Contrast filling in the residual aneurysm was also visualized after Metal Artifact Reduction in every aneurysm. Both the observational (P < .0001) and quantitative (P < .001) analyses showed significant reduction of the metal artifacts after application of the Metal Artifact Reduction prototype software. CONCLUSIONS: The combination of high-resolution C arm CT and Metal Artifact Reduction enables differentiation of the coil mass, stent, and contrast material on the same image by significantly reducing the metal artifacts produced by the platinum coils. This novel image technique may improve the assessment of aneurysms treated with stent-assisted coil embolization. PMID- 26359153 TI - Longitudinal Study of Gray Matter Changes in Parkinson Disease. AB - BACKGROUND AND PURPOSE: The pathology of Parkinson disease leads to morphological brain volume changes. So far, the progressive gray matter volume change across time specific to patients with Parkinson disease compared controls remains unclear. Our aim was to investigate the pattern of gray matter changes in patients with Parkinson disease and to explore the progressive gray matter volume change specific to patients with Parkinson disease with disease progression by using voxel-based morphometry analysis. MATERIALS AND METHODS: Longitudinal cognitive assessment and structural MR imaging of 89 patients with Parkinson disease (62 men) and 55 healthy controls (33 men) were from the Parkinson's Progression Markers Initiative data base, including the initial baseline and 12 month follow-up data. Two-way analysis of covariance was performed with covariates of age, sex, years of education, imaging data from multiple centers, and total intracranial volume by using Diffeomorphic Anatomical Registration Through Exponentiated Lie Algebra tool from SPM8 software. RESULTS: Gray matter volume changes for patients with Parkinson disease were detected with decreased gray matter volume in the frontotemporoparietal areas and the bilateral caudate, with increased gray matter volume in the bilateral limbic/paralimbic areas, medial globus pallidus/putamen, and the right occipital cortex compared with healthy controls. Progressive gray matter volume decrease in the bilateral caudate was found for both patients with Parkinson disease and healthy controls, and this caudate volume was positively associated with cognitive ability for both groups. The progressive gray matter volume increase specific to the patients with Parkinson disease was identified close to the left ventral lateral nucleus of thalamus, and a positive relationship was found between the thalamic volume and the tremor scores in a subgroup with tremor-dominant patients with Parkinson disease. CONCLUSIONS: The observed progressive changes in gray matter volume in Parkinson disease may provide new insights into the neurodegenerative process. The current findings suggest that the caudate volume loss may contribute to cognitive decline in patients with Parkinson disease and the progressive thalamus enlargement may have relevance to tremor severity in Parkinson disease. PMID- 26359155 TI - MRI of Acute Stroke: What Went Wrong? PMID- 26359154 TI - MRI Findings of Disc Degeneration are More Prevalent in Adults with Low Back Pain than in Asymptomatic Controls: A Systematic Review and Meta-Analysis. AB - BACKGROUND AND PURPOSE: Imaging features of spine degeneration are common in symptomatic and asymptomatic individuals. We compared the prevalence of MR imaging features of lumbar spine degeneration in adults 50 years of age and younger with and without self-reported low back pain. MATERIALS AND METHODS: We performed a meta-analysis of studies reporting the prevalence of degenerative lumbar spine MR imaging findings in asymptomatic and symptomatic adults 50 years of age or younger. Symptomatic individuals had axial low back pain with or without radicular symptoms. Two reviewers evaluated each article for the following outcomes: disc bulge, disc degeneration, disc extrusion, disc protrusion, annular fissures, Modic 1 changes, any Modic changes, central canal stenosis, spondylolisthesis, and spondylolysis. The meta-analysis was performed by using a random-effects model. RESULTS: An initial search yielded 280 unique studies. Fourteen (5.0%) met the inclusion criteria (3097 individuals; 1193, 38.6%, asymptomatic; 1904, 61.4%, symptomatic). Imaging findings with a higher prevalence in symptomatic individuals 50 years of age or younger included disc bulge (OR, 7.54; 95% CI, 1.28-44.56; P = .03), spondylolysis (OR, 5.06; 95% CI, 1.65-15.53; P < .01), disc extrusion (OR, 4.38; 95% CI, 1.98-9.68; P < .01), Modic 1 changes (OR, 4.01; 95% CI, 1.10-14.55; P = .04), disc protrusion (OR, 2.65; 95% CI, 1.52-4.62; P < .01), and disc degeneration (OR, 2.24; 95% CI, 1.21 4.15, P = .01). Imaging findings not associated with low back pain included any Modic change (OR, 1.62; 95% CI, 0.48-5.41, P = .43), central canal stenosis (OR, 20.58; 95% CI, 0.05-798.77; P = .32), high-intensity zone (OR = 2.10; 95% CI, 0.73-6.02; P = .17), annular fissures (OR = 1.79; 95% CI, 0.97-3.31; P = .06), and spondylolisthesis (OR = 1.59; 95% CI, 0.78-3.24; P = .20). CONCLUSIONS: Meta analysis demonstrates that MR imaging evidence of disc bulge, degeneration, extrusion, protrusion, Modic 1 changes, and spondylolysis are more prevalent in adults 50 years of age or younger with back pain compared with asymptomatic individuals. PMID- 26359157 TI - Abstracts of the Irish Society of Urology Annual Meeting, 18-19 September 2015, Limerick Strand Hotel, Limerick, Ireland. PMID- 26359156 TI - Outcomes of preterm infants following the introduction of room air resuscitation. AB - BACKGROUND: After 2006 most neonatal intensive care units (NICUs) in Canada stopped initiating newborn resuscitation with 100% oxygen. METHODS: In this retrospective cohort study, we compared neonatal outcomes in infants born at <= 27 weeks gestation that received <100% oxygen (OXtitrate group, typically 21-40% oxygen) during delivery room resuscitation to infants that received 100% oxygen (OX100 group). RESULTS: Data from 17 NICUs included 2326 infants, 1244 in the OXtitrate group and 1082 in the OX100 group. The adjusted odds ratio (AOR) for the primary outcome of severe neurologic injury or death was higher in the OXtitrate group compared with the OX100 group (AOR 1.36; 95% CI 1.11, 1.66). A similar increase was also noted when comparing infants initially resuscitated with room air to the OX100 group (AOR 1.33; 95% CI 1.04, 1.69). Infants in the OXtitrate group were less likely to have received either medical or surgical treatment for a patent ductus arteriosus (AOR 0.53; 95% CI 0.37, 0.74). CONCLUSIONS: In Canadian NICUs, we observed a higher risk of severe neurologic injury or death among preterm infants of <= 27 weeks gestation following a change in practice to initiating resuscitation with either room air or an intermediate oxygen concentration. PMID- 26359158 TI - The adjacent to tumor sample trap. PMID- 26359159 TI - Older adults' outdoor walking and the built environment: does income matter? AB - BACKGROUND: Our aim was to examine the association between Street Smart Walk Score(r) and self-reported outdoor walking among older Canadians, and to determine whether socioeconomic status modifies this association. METHODS: We linked objective walkability data with cross-sectional survey data from the Canadian Community Health Survey Healthy-Aging 2008-2009 Cycle for a sample of 1309 British Columbians aged >= 65 years. We examined associations between Street Smart Walk Score and meeting physical activity guidelines (>=150 min of moderate to vigorous activity/week) through self-reported outdoor walking using multivariable logistic regression, and tested for significant interactions with household income. RESULTS: A ten point higher Street Smart Walk Score was associated with a 17 % higher odds of meeting physical activity guidelines through walking outside (95 % CI: 1.07,1.27). In addition, older adults living in neighbourhoods categorised as Walker's Paradise were over three times more likely to meet guidelines than those living in Car-dependent/Very car dependent neighbourhoods. We found no evidence that household income moderated the effect of Walk Score on walking outside. CONCLUSIONS: Neighbourhood design may be one avenue whereby physical activity levels of older people can be enhanced through outdoor walking, with benefit across socioeconomic strata. PMID- 26359160 TI - Corticosteroids in pediatric ARDS: all cards on the table. PMID- 26359161 TI - Should blood transfusion be individualised? We are not sure. PMID- 26359163 TI - "Not out of the woods"--a wife's perspective: bedside communication. PMID- 26359162 TI - Epidemiology of admissions to 11 stand-alone high-dependency care units in the UK. AB - PURPOSE: High-dependency care units (HDUs) are a focus of research to optimize critical care resource allocation. HDUs provide a level of care between the general ward and the intensive care unit (ICU). However, few data report on the case mix and outcomes of patients in these units. METHODS: Retrospective observational cohort study of patients admitted to 11 stand-alone HDUs in the UK from 2008 to 2011. We stratified patients by location prior to HDU admission and location on discharge from HDU, and we summarized the case mix, transitions of care, and mortality. RESULTS: Of 9008 patients admitted to 11 stand-alone HDUs, 56.5% were male and the mean age was 62.7 +/- 17.9 years. The majority of patients admitted to HDUs were non-surgical (59.3%), with 22.4 and 20.1% admitted from the ICU and general ward, respectively; 41.3% were admitted from the operating room or recovery suite. The median length of stay in HDU was 1.8 days (IQR 0.9-3.5) and in-HDU mortality was 5.1%. Among HDU survivors (n = 8551), 8.5% were discharged to an ICU, 80.9% to a general ward, and 10.6% to other care areas. For patients admitted to HDU from an ICU, only 5.8% were readmitted to ICU. Hospital mortality for the HDU population was 14.8%; for patients discharged to an ICU, hospital mortality was 43.6%. CONCLUSIONS: In a sample of 11 stand alone HDUs in the UK, patients are from many different hospital locations. Hospital mortality for patients requiring HDU care is high, particularly for patients who require transfer to an ICU. PMID- 26359164 TI - Manipulating vital signs in septic shock: which one(s) and how? PMID- 26359165 TI - Contextual effect of selective oral decontamination/selective decontamination of the digestive tract on candidemia: just another word of caution! PMID- 26359166 TI - Early daily mHLA-DR monitoring predicts forthcoming sepsis in severe trauma patients. PMID- 26359167 TI - A newly established extracorporeal life support assisted cardiopulmonary resuscitation (ECPR) program can achieve intact neurological outcome in 60% of children. PMID- 26359168 TI - Impact of multifaceted preventive measures on ventilator-associated pneumonia at a single surgical centre. PMID- 26359169 TI - Constipation is independently associated with delirium in critically ill ventilated patients. PMID- 26359170 TI - The very old ICU patient: a never-ending story. PMID- 26359172 TI - MR spectroscopy, a new in vivo biomarker for dementia disorders? PMID- 26359171 TI - Traumatic brain injury history is associated with earlier age of onset of frontotemporal dementia. AB - OBJECTIVE: We retrospectively examined whether a history of traumatic brain injury (TBI) is associated with an earlier age of symptom onset and diagnosis in a large sample of patients with behavioural variant frontotemporal dementia (bvFTD). METHODS: Data on patients with bvFTD (n=678) were obtained from the National Alzheimer's Coordinating Center Uniform Data Set. TBI was categorised based on reported lifetime history of TBI with loss of consciousness (LOC) but no chronic deficits occurring more than 1 year prior to diagnosis of bvFTD. Analysis of covariance (ANCOVA) was used to determine if clinician-estimated age of symptom onset and age at diagnosis of bvFTD differed between those who reported a history of TBI with LOC (TBI+) and those who did not (TBI-). RESULTS: Controlling for sex, the TBI+ bvFTD group had an age of symptom onset and age of diagnosis that was on average 2.8 and 3.2 years earlier (p<0.01) than the TBI- bvFTD group. CONCLUSIONS: TBI history with LOC occurring more than 1 year prior to diagnosis is associated with an earlier age of symptom onset and diagnosis in patients with bvFTD. TBI may be related to the underlying neurodegenerative processes in bvFTD, but the implications of age at time of injury, severity and repetitive injuries remain unclear. PMID- 26359173 TI - Prevalence and correlates of suicidal thoughts in patients with neuropsychiatric lupus. AB - BACKGROUND: Suicidal ideation is observed in patients with systemic lupus erythematosus (SLE). No study on this notable phenomenon in neuropsychiatric SLE (NPSLE) is available so far. METHODS: Participants were 53 consecutive outpatients with NPSLE (48 women; mean age 43.8 years) diagnosed according to the American College of Rheumatology nomenclature for SLE neuropsychiatric syndromes. A Neuropsychiatric Questionnaire (NP-Q) concerning 45 neurological, cognitive and psychiatric symptoms was used to assess the prevalence of self-perceived neuropsychiatric symptoms. The Modified Hospital Anxiety and Depression Scale (HADS-M) was used to assess the level of anxiety, depression and irritability. Formal neuropsychological examination was performed. Clinical data were collected by means of medical charts review and structured interview. RESULTS: Suicidal thoughts were present in 25% of patients with NPSLE, irrespective of sex, age, education, work status, disease duration and steroid treatment. Suicidal ideation was connected with elevated levels of depression, anxiety and irritability. In patients with suicidal ideation the prevalence of cognitive, psychiatric and neurological self-perceived problems was significantly higher. CONCLUSIONS: Suicidal thoughts are common in patients with NPSLE. Neuropsychiatric manifestation per se, depression, anxiety and patients' subjective complaints can be risk factors for suicidal ideation. Screening for suicidal thoughts is vital in routine care of SLE patients. PMID- 26359174 TI - Metabolic syndrome is associated with decreased circulating endothelial progenitor cells and increased arterial stiffness in systemic lupus erythematosus. AB - OBJECTIVES: Metabolic syndrome (MetS) is highly prevalent in patients with systemic lupus erythematosus (SLE) and it has been associated with increased cardiovascular risk. We examined the contribution of MetS to inflammatory markers, arterial stiffness and circulating endothelial progenitor cells (EPCs) as surrogates of subclinical atherosclerosis. METHODS: Cardiovascular risk factors, SLE-specific factors and peripheral blood EPCs were assessed in 50 female SLE patients. MetS was defined according to the National Cholesterol Education Program Adult Treatment Panel III. Simultaneously, atherosclerosis was assessed by measuring the carotid-femoral pulse wave velocity (PWV) by doppler velocimetry. RESULTS: Beyond the factors included in the definition, SLE patients with MetS have a significantly higher serum level of uric acid (6.88 +/- 2.20 vs 4.45 +/- 1.17, p < 0.001) and some inflammatory biomarkers such as homocysteine, IL-8, sICAM-1 or complement molecules. The presence of MetS in our patients was closely linked with a significantly increased patient organ damage score (3.20 +/ 1.97 vs 1.60 +/- 1.67, p = 0.008), a decreased percentage of circulating EPCs (0.53 +/- 0.24 vs 0.85 +/- 0.57, p = 0.007) and an increased arterial stiffness (9.89 +/- 2.40 vs 7.13 +/- 1.51, p < 0.001). CONCLUSIONS: MetS may contribute to the development of atherosclerosis by significantly increasing inflammation levels and arterial stiffness and decreasing circulating EPCs. This finding would justify close monitoring of these patients. PMID- 26359175 TI - Molecular evolution and in vitro characterization of Botryllus histocompatibility factor. AB - Botryllus schlosseri is a colonial ascidian with a natural ability to anastomose with another colony to form a vascular and hematopoietic chimera. In order to fuse, two individuals must share at least one allele at the highly polymorphic fuhc locus. Otherwise, a blood-based inflammatory response will occur resulting in a melanin scar at the sites of interaction. The single-locus genetic control of allorecognition makes B. schlosseri an attractive model to study the underlying molecular mechanisms. Over the past decade, several candidate genes involved in allorecognition have been identified, but how they ultimately contribute to allorecognition outcome remains poorly understood. Here, we report our initial molecular characterization of a recently identified candidate allodeterminant called Botryllus histocompatibility factor (bhf). bhf, both on a DNA and protein level, is the least polymorphic protein in the fuhc locus studied so far and, unlike other known allorecognition determinants, does not appear to be under any form of balancing or directional selection. Additionally, we identified a second isoform through mRNA-Seq and an EST assembly library which is missing exon 3, resulting in a C-terminally truncated form. We report via whole mount fluorescent in situ hybridization that a subset of cells co-express bhf and cfuhc(sec). Finally, we observed BHF's localization in HEK293T at the cytoplasmic side of the plasma membrane in addition to the nucleus via a nuclear localization signal. Given the localization data thus far, we hypothesize that BHF may function as a scaffolding protein in a complex with other Botryllus proteins, rather than functioning as an allorecognition determinant. PMID- 26359176 TI - A mechanical pivot-shift device for continuously applying defined loads to cadaveric knees. AB - PURPOSE: Current techniques to study the biomechanics of the pivot-shift utilize either static or poorly defined loading conditions. Here, a novel mechanical pivot-shift device that continuously applies well-defined loads to cadaveric knees is characterized and validated against the manual pivot-shift. METHODS: Six fresh-frozen human lower limb specimens were potted at the femur, mounted on a hinged testing base, and fitted with the mechanical device. Five mechanical and manual pivot-shift tests were performed on each knee by two examiners before and after transecting the ACL. Three-dimensional kinematics (anterior and internal rotary displacements, and posterior and external-rotary velocities) and kinetics (forces and moments applied to the tibia by the device) were recorded using an optical navigation system and 6-axis load cell. Analysis of variance and Bland Altman statistics were used to gauge repeatability within knees, reproducibility between knees, agreement between the mechanical and manual test methods, and agreement between examiners. RESULTS: The forces and moments applied by the device were continuous and repeatable/reproducible to within 4/10 % of maximum recorded values. Kinematic variables (excluding external-rotary velocity) were qualitatively and quantitatively similar to manual pivot-shift kinematics, and were more repeatable and reproducible. CONCLUSION: The presented device induces pivot-shift-like kinematics by applying highly repeatable three-dimensional loads to cadaver knees. It is based on a simple mechanical principle and designed using easily obtainable components. Consequently, the device enables orthopaedic biomechanists to easily and reliably quantify the effect of ACL injury and reconstruction on pivot-shift kinematics. PMID- 26359177 TI - Robotic axial lower leg testing: repeatability and reproducibility. AB - PURPOSE: The purpose of this study was to determine the test-retest reliability and the repeatability over multiple days of a robotic testing device when used to measure laxity of the lower leg during a simulated dial test. METHODS: Ten healthy subjects were evaluated using an instrumented robotic lower leg testing system over 4 days. Three testing cycles were performed each day. Each leg was rotated into external and then internal rotation by servomotors until a torque threshold of 5.65 N m was reached. Load-deformation curves were generated from torque and rotation data. Both average-measure and single-measure intraclass correlation coefficients (ICC) were compared across the curves. ICC scores were also compared for features of the curves including: maximum external rotation at 5.65 N m of torque, maximum internal rotation at 5.65 N m of torque, rotation at torque 0, compliance (slope of load-deformation curve) at torque 0, endpoint compliance in external rotation, endpoint compliance in internal rotation, and play at torque 0. Play at torque 0 was defined as the width of the hysteresis curve at torque 0. RESULTS: Average-measure ICC scores and test-retest scores were >0.95 along the entire load-deformation curve except around zero torque. ICC scores at maximum internal and external rotation ranged from 0.87 to 0.99 across the left and right knees. ICC scores for the other features of the curves ranged from 0.61 to 0.98. The standard error of the mean ranged from 0.0497 to 1.1712. CONCLUSIONS: The robotic testing device in this study proved to be reliable for testing a subject multiple times both within the same day and over multiple days. These findings suggest that the device can provide a level of reliability in rotational testing that allows for clinical use of test results. Objective laxity data can improve consistency and accuracy in diagnosing knee injuries and may enable more effective treatment. PMID- 26359178 TI - Transanal endoscopic resection with peritoneal entry: a word of reason. PMID- 26359179 TI - Long-term outcomes after circular stapled hemorrhoidopexy versus Ferguson hemorrhoidectomy. AB - BACKGROUND: We aimed to compare long-term outcomes and quality of life in patients undergoing circular stapled hemorrhoidopexy to those who had Ferguson hemorrhoidectomy. METHODS: Patients who underwent Ferguson hemorrhoidectomy and circular stapled hemorrhoidopexy between 2000 and 2010 were reviewed. Long-term follow-up was assessed with questionnaires. RESULTS: Two hundred seventeen patients completed the questionnaires. Mean follow-up was longer in the Ferguson hemorrhoidectomy subgroups (7.7 +/- 3.4 vs. 6.3 +/- 2.9 years, p = 0.003). Long term need for additional surgical or medical treatment was similar in the Ferguson hemorrhoidectomy and circular stapled hemorrhoidopexy groups (3 vs. 5%, p = 0.47 and 3% in both groups, p > 0.99, respectively). Eighty-one percentage of Ferguson hemorrhoidectomy and 83% of circular stapled hemorrhoidopexy patients stated that they would undergo hemorrhoid surgery again if needed (p = 0.86). The symptoms were greatly improved in the majority of patients (p = 0.06), and there was no difference between the groups as regards long-term anorectal pain (p = 0.16). The Cleveland global quality of life, fecal incontinence severity index, and fecal incontinence quality of life scores were similar (p > 0.05). CONCLUSIONS: This is one of the longest follow-up studies comparing the outcomes after circular stapled hemorrhoidopexy and Ferguson hemorrhoidectomy. Patient satisfaction, resolution of symptoms, quality of life, and functional outcome appear similar after circular stapled hemorrhoidopexy and Ferguson hemorrhoidectomy in long term. PMID- 26359180 TI - Weight outcomes audit in 1.3 million adults during their first 3 months' attendance in a commercial weight management programme. AB - BACKGROUND: Over sixty percent of adults in the UK are now overweight/obese. Weight management on a national scale requires behavioural and lifestyle solutions that are accessible to large numbers of people. Evidence suggests commercial weight management programmes help people manage their weight but there is little research examining those that pay to attend such programmes rather than being referred by primary care. The objective of this analysis was to evaluate the effectiveness of a UK commercial weight management programme in self referred, fee-paying participants. METHODS: Electronic weekly weight records were collated for self-referred, fee-paying participants of Slimming World groups joining between January 2010 and April 2012. This analysis reports weight outcomes in 1,356,105 adult, non-pregnant participants during their first 3 months' attendance. Data were analysed by regression, ANOVA and for binomial outcomes, chi-squared tests using the R statistical program. RESULTS: Mean (SD) age was 42.3 (13.6) years, height 1.65 m (0.08) and start weight was 88.4 kg (18.8). Mean start BMI was 32.6 kg/m(2) (6.3 kg/m(2)) and 5 % of participants were men. Mean weight change of all participants was -3.9 kg (3.6), percent weight change -4.4 (3.8), and BMI change was -1.4 kg/m(2) (1.3). Mean attendance was 7.8 (4.3) sessions in their first 3 months. For participants attending at least 75 % of possible weekly sessions (n = 478,772), mean BMI change was -2.5 kg/m(2) (1.3), weight change -6.8 kg (3.7) and percent weight change -7.5 % (3.5). Weight loss was greater in men than women absolutely (-6.5 (5.3) kg vs 3.8 (3.4) kg) and as a percentage (5.7 % (4.4) vs 4.3 % (3.7)), respectively. All comparisons were significant (p < 0.001). Level of attendance and percent weight loss in the first week of attendance together accounted for 55 % of the variability in weight lost during the study period. CONCLUSIONS: A large-scale commercial lifestyle-based weight management programme had a significant impact on weight loss outcomes over 3 months. Higher levels of attendance led to levels of weight loss known to be associated with significant clinical benefits, which on this scale may have an impact on public health. PMID- 26359181 TI - Ecology and application of haloalkaliphilic anaerobic microbial communities. AB - Haloalkaliphilic microorganisms that grow optimally at high-pH and high-salinity conditions can be found in natural environments such as soda lakes. These globally spread lakes harbour interesting anaerobic microorganisms that have the potential of being applied in existing technologies or create new opportunities. In this review, we discuss the potential application of haloalkaliphilic anaerobic microbial communities in the fermentation of lignocellulosic feedstocks material subjected to an alkaline pre-treatment, methane production and sulfur removal technology. Also, the general advantages of operation at haloalkaline conditions, such as low volatile fatty acid and sulfide toxicity, are addressed. Finally, an outlook into the main challenges like ammonia toxicity and lack of aggregation is provided. PMID- 26359182 TI - Metagenome approaches revealed a biological prospect for improvement on mesophilic cellulose degradation. AB - Improvement on the bioconversion of cellulosic biomass depends much on the expanded knowledge on the underlying microbial structure and the relevant genetic information. In this study, metagenomic analysis was applied to characterize an enriched mesophilic cellulose-converting consortium, to explore its cellulose hydrolyzing genes, and to discern genes involved in methanogenesis. Cellulose conversion efficiency of the mesophilic consortium enriched in this study was around 70 %. Apart from methane, acetate was the major fermentation product in the liquid phase, while propionate and butyrate were also detected at relatively high concentrations. With the intention to uncover the biological factors that might shape the varying cellulose conversion efficiency at different temperatures, results of this mesophilic consortium were then compared with that of a previously reported thermophilic cellulose-converting consortium. It was found that the mesophilic consortium harbored a larger pool of putative carbohydrate-active genes, with 813 of them in 54 GH modules and 607 genes in 13 CBM modules. Methanobacteriaceae and Methanosaetaceae were the two methanogen families identified, with a preponderance of the hydrogenotrophic Methanobacteriaceae. In contrast to its relatively high diversity and high abundance of carbohydrate-active genes, the abundance of genes involved in the methane metabolism was comparatively lower in the mesophilic consortium. A biological enhancement on the methanogenic process might serve as an effective option for the improvement of the cellulose bioconversion at mesophilic temperature. PMID- 26359183 TI - Erratum to: Odanacatib for the treatment of postmenopausal osteoporosis: development history and design and participant characteristics of LOFT, the Long Term Odanacatib Fracture Trial. PMID- 26359186 TI - Rethinking the paradigm: How comparative studies on fatty acid oxidation inform our understanding of T cell metabolism. AB - The classic paradigm of T cell metabolism posits that activated Teff cells utilize glycolysis to keep pace with increased energetic demands, while resting and Tmem cells rely on the oxidation of fat. In contrast, Teff cells during graft versus-host disease (GVHD) increase their reliance on oxidative metabolism and, in particular, on fatty acid oxidation (FAO). To explore the potential mechanisms driving adoption of this alternative metabolism, we first review key pathways regulating FAO across a variety of disparate tissue types, including liver, heart, and skeletal muscle. Based upon these comparative studies, we then outline a consensus network of transcriptional and signaling pathways that predict a model for regulating FAO in Teff cells during GVHD. This model raises important implications about the dynamic nature of metabolic reprogramming in T cells and suggests exciting future directions for further study of in vivo T cell metabolism. PMID- 26359184 TI - The associations of physical activity with fracture risk--a 7-year prospective controlled intervention study in 3534 children. AB - SUMMARY: This is the first study indicating an association between gradually diminished risk of fractures and years of increased physical activity. Our results could imply great benefits not only for the individual but also for the healthcare burden and cost of society. INTRODUCTION: Physical activity (PA) in childhood is associated with high bone mass and beneficial neuromuscular function. We investigate if increased PA also is associated with fracture risk. METHODS: We registered fractures in 3534 children aged 6 to 8 years at study start for up to 7 years; 1339 with 40 min of moderate PA every school day (intervention) and 2195 with the Swedish standard curriculum of 60 min of PA per school week (controls). In a subsample of 264 children, we measured areal bone mineral density (aBMD; g/cm(2)) with dual-energy X-ray absorptiometry (femoral neck and total spine) and muscle strength (peak torque for knee extension and flexion; Nm) with computerized dynamometer at baseline and after 7 years. We estimated annual fracture incidence rate ratios (IRR) in the intervention group compared to the control group as well as changes in bone mass and muscle strength. Data is given as mean (95% CI). RESULTS: The IRR of fractures decreased with each year of the PA intervention (r = -0.79; p = 0.04). During the seventh year, IRR was almost halved [IRR 0.52 (0.27, 1.01)]. The intervention group had a statistically significant greater gain in total spine aBMD with a mean group difference of 0.03 (0.00, 0.05) g/cm(2) and peak flexion torque 180 degrees with a mean group difference of 5.0 (1.5, 8.6) Nm. CONCLUSIONS: Increased PA is associated with decreased fracture risk, probably in part due to beneficial gains in aBMD and muscle strength. PMID- 26359187 TI - Cretaceous collegiality. PMID- 26359185 TI - Association of 25-hydroxyvitamin D with areal and volumetric measures of bone mineral density and parathyroid hormone: impact of vitamin D-binding protein and its assays. AB - A comparison of the association of different forms of 25-hydroxyvitamin D [25(OH)D] with parathyroid hormone (PTH) and with areal and volumetric bone mineral density (BMD) demonstrated that bioavailable and free 25(OH)D do not provide a better index of vitamin D status in terms of bone health compared to total 25(OH)D. INTRODUCTION: This study aims to compare measures of vitamin D binding protein (DBP) using a monoclonal versus polyclonal ELISA and assess correlations of total versus estimated free and bioavailable 25(OH)D with BMD and PTH concentrations. METHODS: DXA and peripheral quantitative CT (pQCT) scans were obtained in 304 adults (158 black, 146 white), ages 21-80 years. Free and bioavailable 25(OH)D were calculated from total 25(OH)D, DBP, and albumin concentrations. Multivariable linear regression with standardized beta coefficients was used to evaluate associations of bone measures and PTH with total, free, and bioavailable 25(OH)D. RESULTS: Measures of DBP obtained using a monoclonal versus polyclonal ELISA were not correlated (r s = 0.02, p = 0.76). Free and bioavailable 25(OH)D based on the polyclonal assay were lower in black versus white participants (p < 0.0001); this race difference was not evident using the monoclonal assay. Adjusted for age, sex, calcium intake, and race, all forms of 25(OH)D were negatively associated with PTH, but the absolute coefficient was greatest for total 25(OH)D (-0.34, p < 0.001) versus free/bioavailable 25(OH)D (-0.18/-0.24 depending on DBP assay, p <= 0.003). In analyses stratified on race, none of the measures of 25(OH)D were associated with BMD across DXA and pQCT sites. CONCLUSIONS: The monoclonal versus polyclonal ELISA yielded highly discrepant measures of DBP, particularly among black individuals, likely related to established race differences in DBP polymorphisms. Contrary to prior studies, our findings indicate that using DBP to estimate bioavailable and free 25(OH)D does not provide a better index of vitamin D status in terms of bone health. PMID- 26359189 TI - Anterior Segment Imaging Predicts Incident Gonioscopic Angle Closure. AB - PURPOSE: To investigate the incidence of gonioscopic angle closure after 4 years in subjects with gonioscopically open angles but varying degrees of angle closure detected on anterior segment optical coherence tomography (AS OCT; Visante; Carl Zeiss Meditec, Dublin, CA) at baseline. DESIGN: Prospective, observational study. PARTICIPANTS: Three hundred forty-two subjects, mostly Chinese, 50 years of age or older, were recruited, of whom 65 were controls with open angles on gonioscopy and AS OCT at baseline, and 277 were cases with baseline open angles on gonioscopy but closed angles (1-4 quadrants) on AS OCT scans. METHODS: All subjects underwent gonioscopy and AS OCT at baseline (horizontal and vertical single scans) and after 4 years. The examiner performing gonioscopy was masked to the baseline and AS OCT data. Angle closure in a quadrant was defined as nonvisibility of the posterior trabecular meshwork by gonioscopy and visible iridotrabecular contact beyond the scleral spur in AS OCT scans. MAIN OUTCOME MEASURES: Gonioscopic angle closure in 2 or 3 quadrants after 4 years. RESULTS: There were no statistically significant differences in age, ethnicity, or gender between cases and controls. None of the control subjects demonstrated gonioscopic angle closure after 4 years. Forty-eight of the 277 subjects (17.3%; 95% confidence interval [CI], 12.8-23; P < 0.0001) with at least 1 quadrant of angle closure on AS OCT at baseline demonstrated gonioscopic angle closure in 2 or more quadrants, whereas 28 subjects (10.1%; 95% CI, 6.7-14.6; P < 0.004) demonstrated gonioscopic angle closure in 3 or more quadrants after 4 years. Individuals with more quadrants of angle closure on baseline AS OCT scans had a greater likelihood of gonioscopic angle closure developing after 4 years (P < 0.0001, chi-square test for trend for both definitions of angle closure). CONCLUSIONS: Anterior segment OCT imaging at baseline predicts incident gonioscopic angle closure after 4 years among subjects who have gonioscopically open angles and iridotrabecular contact on AS OCT at baseline. PMID- 26359190 TI - Intramuscular granular cell tumor: emphasizing the stripe sign. AB - We present a case of an intramuscular granular cell tumor in the thigh manifesting a 'stripe sign' on magnetic resonance imaging (MRI). This MR finding may correspond with the entrapped muscle fibers within the tumor, which demonstrated parallel arrangement on histopathologic examination. In addition, other disease entities characterized by the presence of this sign such as proliferative myositis, heterotopic ossification, and muscular sarcoidosis will be reviewed. PMID- 26359192 TI - Diet-induced changes in iron and n-3 fatty acid status and associations with cognitive performance in 8-11-year-old Danish children: secondary analyses of the Optimal Well-Being, Development and Health for Danish Children through a Healthy New Nordic Diet School Meal Study. AB - Fe and n-3 long-chain PUFA (n-3 LCPUFA) have both been associated with cognition, but evidence remains inconclusive in well-nourished school-aged children. In the Optimal Well-Being, Development and Health for Danish Children through a Healthy New Nordic Diet (OPUS) School Meal Study, the 3-month intervention increased reading performance, inattention, impulsivity and dietary intake of fish and Fe. This study investigated whether the intervention influenced n-3 LCPUFA and Fe status and, if so, explored how these changes correlated with the changes in cognitive performance. The study was a cluster-randomised cross-over trial comparing school meals with packed lunch (control). At baseline and after each treatment, we measured serum ferritin, whole-blood n-3 LCPUFA and Hb, and performance in reading, mathematics and d2-test of attention. Data were analysed using mixed models (n 726) and principal component analysis of test performances (n 644), which showed two main patterns: 'school performance' and 'reading comprehension'. The latter indicated that children with good reading comprehension were also more inattentive and impulsive (i.e. higher d2-test error%). The intervention improved 'school performance' (P=0.015), 'reading comprehension' (P=0.043) and EPA+DHA status 0.21 (95% CI 0.15, 0.27) w/w % (P<0.001), but it did not affect serum ferritin or Hb. At baseline, having small Fe stores was associated with poorer 'school performance' in girls, but with better 'reading comprehension' in both boys and girls. Both baseline EPA+DHA status and the intervention-induced increase in EPA+DHA status was positively associated with 'school performance', suggesting that n-3 LCPUFA could potentially explain approximately 20 % of the intervention effect. These exploratory associations indicate that increased fish intake might explain some of the increase in reading performance and inattention in the study. PMID- 26359193 TI - Reconciling Environment and Production in Managed Ecosystems: Is Ecological Intensification a Solution? PMID- 26359191 TI - Comparison of (18)F-fluorodeoxyglucose positron emission tomography (FDG PET) and cardiac magnetic resonance (CMR) in corticosteroid-naive patients with conduction system disease due to cardiac sarcoidosis. AB - PURPOSE: Cardiac sarcoidosis (CS) is a cause of conduction system disease (CSD). (18)F-Fluorodeoxyglucose-positron emission tomography (FDG PET) and cardiac magnetic resonance (CMR) are used for detection of CS. The relative diagnostic value of these has not been well studied. The aim was to compare these imaging modalities in this population. METHODS: We recruited steroid-naive patients with newly diagnosed CSD due to CS. All CS patients underwent both imaging studies within 12 weeks of each other. Patients were classified into two groups: group A with chronic mild CSD (right bundle branch block and/or axis deviation), and group B with new-onset atrioventricular block (AVB, Mobitz type II or third degree AVB). RESULTS: Thirty patients were included. Positive findings on both imaging studies were seen in 72 % of patients (13/18) in group A and in 58 % of patients (7/12) in group B. The remainder (28 %) of the patients in group A were positive only on CMR. Of the patients in group B, 8 % were positive only on CMR and 33 % were positive only on FDG PET. Patients in group A were more likely to be positive only on CMR, and patients in group B were more likely to be positive only on FDG PET (p = 0.02). Patients in group B positive only on FDG PET underwent CMR earlier relative to their symptomatology than patients positive only on CMR (median 7.0, IQR 1.5 - 34.3, vs. 72.0, IQR 25.0 - 79.5 days; p = 0.03). CONCLUSION: The number of positive FDG PET and CMR studies was different in patients with CSD depending on their clinical presentation. This study demonstrated that CMR can adequately detect cardiac involvement associated with chronic mild CSD. In patients presenting with new-onset AVB and a negative CMR study, FDG PET may be useful for detecting cardiac involvement due to CS. PMID- 26359194 TI - Essential Surgery: The Way Forward: Reply. PMID- 26359195 TI - Opponent's comments. PMID- 26359196 TI - Opponent's comments. PMID- 26359197 TI - Con: Weight loss prior to transplant: no. AB - In large registries of hemodialysis patients, higher body mass index (BMI) is known to be associated with lower mortality rates, while weight loss associates with reduced survival. This so-called 'obesity paradox' includes patients categorized as overweight and obese. Transplantation in the obese patient population has been shown to improve quality of life and reduce mortality when compared with obese recipient candidates remaining on dialysis. Most transplant centers, however, restrict access to transplant based upon predetermined BMI cutoffs. This policy effectively mandates weight loss for many obese transplant candidates. However, BMI, though easily measured, is an inadequate assessment of nutritional status and lean muscle mass in obese patients. Regimens designed to prevent protein-energy wasting may include dietary recommendations and exercise programs that result in favorable changes in body composition without significantly impacting weight. The goal of weight loss is not achievable for many if not most obese dialysis patients. The consequence to the patient is reduced access to life improving transplantation. Patients are forced to pursue dietary, behavioral and possibly surgical interventions to accomplish weight loss despite limited evidence regarding the safety and utility of these interventions. The delay in transplantation also hinders the achievement of improved exercise capacity after successful transplant, a time when weight loss regimens may be safer and more effective. PMID- 26359198 TI - Moderator's view: Pretransplant weight loss in dialysis patients: cum grano salis. AB - A high Body Mass Index (BMI) predicts delayed graft function, all cause and cardiovascular death after transplantation but such risk excess is apparently confined to patients included in studies performed before 2000. Perhaps with the exception of morbid obesity (BMI > 40), clinical outcomes in transplanted obese patients are definitely better than in listed dialysis patients who don't receive a renal transplant. Furthermore the new Scientific Registry of Transplant Recipients (SRTR) risk calculator incorporates BMI into the prediction model of the global risk for the graft's and patient's survival appropriately framing the risk of obesity in a multidimensional risk context. In the aggregate, available knowledge suggests that clinical decisions on weight loss before transplantation should be context specific. Renal transplant patients from living donors have substantial better survival in comparison to well matched dialysis patients listed for the same intervention at all BMI categories. Therefore renal transplantation in obese patients with a living donor may be prioritized. The attitude of fully informed obese patients at accepting the risk driven by transplantation, the experience of the surgical team with obese patients (including also robotic surgery) are of obvious importance. Renal transplantation should be timely considered when reasonable attempts at weight loss failed or appear overtly unrealistic. Transplantation in morbidly obese patients with BMI > 40, a category where the survival advantage of transplantation vs dialysis is probably small and still uncertain, particularly so in African-Americans, should be deferred until significant weight loss is achieved. PMID- 26359199 TI - Pro: Pretransplant weight loss: yes. AB - The obesity epidemic has not spared the population with renal failure. Obesity impacts prognosis after kidney transplantation, as markers of obesity are associated with worse outcomes (e.g. delayed graft function, graft failure, cardiovascular disease, costs) compared with ideal values in most studies. Obesity is also potentially modifiable. Kidney transplants are a scarce resource and the obligation to steward organs to good outcomes is inherent in transplant practice. Thus, it is appropriate to establish pretransplant weight loss targets and engage obese patients seeking transplantation in shared responsibility agreements to strive to reach goals. Nonetheless, important caveats may qualify the stringency of pretransplant weight loss requirements. Obese patients (who are otherwise healthy enough for transplant) may benefit from transplantation compared with long-term dialysis based on metrics such as improved long-term survival and lower cardiac risk. When optimal weight loss is difficult to achieve, factors in a given program's ability to extend the limits of obesity acceptable for safe and effective transplantation include expertise (e.g. surgical approaches and clinical management), tolerance for risk based on overall performance and tolerance for costs. More research is needed, including formal cost-effectiveness studies of transplantation in obese patients to determine if payers (e.g. Medicare) and society should be compensating programs for clinical and financial risks, and whether the risks are worth taking. To generate evidence to better guide management, prospective evaluations of the impact of intentional weight loss strategies in this population, including studies of dietary change, monitored exercise and bariatric surgery, are also urgently needed. PMID- 26359200 TI - Peritoneal dialysis or haemodialysis in end-stage renal disease: do registry data matter? PMID- 26359201 TI - Neurological complications in chronic kidney disease patients. AB - Chronic kidney disease (CKD) is associated with a high prevalence of cerebrovascular disorders such as stroke, white matter diseases, intracerebral microbleeds and cognitive impairment. This situation has been observed not only in end-stage renal disease patients but also in patients with mild or moderate CKD. The occurrence of cerebrovascular disorders may be linked to the presence of traditional and non-traditional cardiovascular risk factors in CKD. Here, we review current knowledge on the epidemiological aspects of CKD-associated neurological and cognitive disorders and discuss putative causes and potential treatment. CKD is associated with traditional (hypertension, hypercholesterolaemia, diabetes etc.) and non-traditional cardiovascular risk factors such as elevated levels of oxidative stress, chronic inflammation, endothelial dysfunction, vascular calcification, anaemia and uraemic toxins. Clinical and animal studies indicate that these factors may modify the incidence and/or outcomes of stroke and are associated with white matter diseases and cognitive impairment. However, direct evidence in CKD patients is still lacking. A better understanding of the factors responsible for the elevated prevalence of cerebrovascular diseases in CKD patients may facilitate the development of novel treatments. Very few clinical trials have actually been performed in CKD patients, and the impact of certain treatments is subject to debate. Treatments that lower LDL cholesterol or blood pressure may reduce the incidence of cerebrovascular diseases in CKD patients, whereas treatment with erythropoiesis stimulating agents may be associated with an increased risk of stroke but a decreased risk of cognitive disorders. The impact of therapeutic approaches that reduce levels of uraemic toxins has yet to be evaluated. PMID- 26359202 TI - Light-induced metal-like surface of silicon photonic waveguides. AB - The surface of a material may exhibit physical phenomena that do not occur in the bulk of the material itself. For this reason, the behaviour of nanoscale devices is expected to be conditioned, or even dominated, by the nature of their surface. Here, we show that in silicon photonic nanowaveguides, massive surface carrier generation is induced by light travelling in the waveguide, because of natural surface-state absorption at the core/cladding interface. At the typical light intensity used in linear applications, this effect makes the surface of the waveguide behave as a metal-like frame. A twofold impact is observed on the waveguide performance: the surface electric conductivity dominates over that of bulk silicon and an additional optical absorption mechanism arises, that we named surface free-carrier absorption. These results, applying to generic semiconductor photonic technologies, unveil the real picture of optical nanowaveguides that needs to be considered in the design of any integrated optoelectronic device. PMID- 26359203 TI - Magnetic fingerprint of individual Fe4 molecular magnets under compression by a scanning tunnelling microscope. AB - Single-molecule magnets (SMMs) present a promising avenue to develop spintronic technologies. Addressing individual molecules with electrical leads in SMM-based spintronic devices remains a ubiquitous challenge: interactions with metallic electrodes can drastically modify the SMM's properties by charge transfer or through changes in the molecular structure. Here, we probe electrical transport through individual Fe4 SMMs using a scanning tunnelling microscope at 0.5 K. Correlation of topographic and spectroscopic information permits identification of the spin excitation fingerprint of intact Fe4 molecules. Building from this, we find that the exchange coupling strength within the molecule's magnetic core is significantly enhanced. First-principles calculations support the conclusion that this is the result of confinement of the molecule in the two-contact junction formed by the microscope tip and the sample surface. PMID- 26359204 TI - Waveguide integrated superconducting single-photon detectors implemented as near perfect absorbers of coherent radiation. AB - At the core of an ideal single-photon detector is an active material that absorbs and converts every incident photon to a discriminable signal. A large active material favours efficient absorption, but often at the expense of conversion efficiency, noise, speed and timing accuracy. In this work, short (8.5 MUm long) and narrow (8 * 35 nm(2)) U-shaped NbTiN nanowires atop silicon-on-insulator waveguides are embedded in asymmetric nanobeam cavities that render them as near perfect absorbers despite their small volume. At 2.05 K, when biased at 0.9 of the critical current, the resulting superconducting single-photon detectors achieve a near-unity on-chip quantum efficiency for ~1,545 nm photons, an intrinsic dark count rate <0.1 Hz, a reset time of ~7 ns, and a timing jitter of ~55 ps full-width at half-maximum. Such ultracompact, high-performance detectors are essential for progress in integrated quantum optics. PMID- 26359188 TI - Outcome of Treatment of Uveitic Macular Edema: The Multicenter Uveitis Steroid Treatment Trial 2-Year Results. AB - PURPOSE: To evaluate the 2-year outcomes of uveitic macular edema. DESIGN: Longitudinal follow-up of a randomized cohort. PARTICIPANTS: At baseline, 148 eyes of 117 patients enrolled in the Multicenter Uveitis Steroid Treatment (MUST) Trial had macular edema, and 134 eyes of 108 patients completed 2-year follow-up. METHODS: Patients enrolled in the study were randomized to either systemic immunosuppression or intravitreal fluocinolone acetonide implant therapy. Macular edema was defined as thickening of the retina (center point thickness>=240 MUm) on time-domain optical coherence tomography (OCT) of macula. MAIN OUTCOME MEASURES: Improvement in macular edema (>=20% reduction in central point thickness on OCT), resolution of macular edema (normalization of thickness on OCT), and best-corrected visual acuity (BCVA). RESULTS: Between randomization and 2-years' follow-up, 62% and 25% of eyes in the systemic and implant groups, respectively, received at least 1 supplemental regional corticosteroid injection. By 2-years' follow-up, macular edema improved in 71% of eyes and resolved in 60%. There were no differences between treatment groups in the proportion of eyes with macular edema improving (systemic therapy vs. implant, 65% vs. 77%; P=0.20) and resolving (52% vs. 68%; P=0.28), but eyes randomized to implant had more improvement in macular thickness (median decrease of 180 vs. 109 MUm in the systemic therapy group; P=0.04). Eyes with baseline fluorescein angiographic leakage were more likely to improve than those without (76% vs. 58%; P=0.03). Overall, there was a mean 5-letter (1 line) improvement in BCVA at 2 years. Mean changes in BCVA from baseline at 2 years by macular edema response status were: resolution, +10 letters; improvement without resolution, +10 letters (P=0.92); little to no change, 6 letters (P=0.19); and worsening, -16 letters (worsening acuity; P=0.0003). CONCLUSIONS: About two thirds of eyes with uveitic macular edema were observed to experience improvement in the edema and visual acuity with implant or systemic treatment. Fluocinolone acetonide implant therapy was associated with a greater quantitative improvement in thickness. Fluorescein angiography leakage was associated with a greater likelihood of improvement in macular edema. PMID- 26359205 TI - Enigmatic meningitis in a patient with T cell lymphoma. PMID- 26359206 TI - Strong correlations elucidate the electronic structure and phase diagram of LaAlO3/SrTiO3 interface. AB - The interface between the two band insulators SrTiO3 and LaAlO3 has the unexpected properties of a two-dimensional electron gas. It is even superconducting with a transition temperature, T(c), that can be tuned using gate bias V(g), which controls the number of electrons added or removed from the interface. The gate bias-temperature (V(g), T) phase diagram is characterized by a dome-shaped region where superconductivity occurs, that is, T(c) has a non monotonic dependence on V(g), similar to many unconventional superconductors. Here, we report, the frequency of the quantum resistance-oscillations versus inverse magnetic field for various V(g). This frequency follows the same non monotonic behaviour as T(c); a similar trend is seen in the low field limit of the Hall coefficient. We theoretically show that electronic correlations result in a non-monotonic population of the mobile band, which can account for the experimental behaviour of the normal transport properties and the superconducting dome. PMID- 26359207 TI - Emergent surface superconductivity in the topological insulator Sb2Te3. AB - Surfaces of three-dimensional topological insulators have emerged as one of the most remarkable states of condensed quantum matter where exotic electronic phases of Dirac particles should arise. Here we report on superconductivity in the topological insulator Sb2Te3 with transition to zero resistance induced through a minor tuning of growth chemistry that depletes bulk conduction channels. The depletion shifts Fermi energy towards the Dirac point as witnessed by a factor of 300 reduction of bulk carrier density and by the largest carrier mobility (?25,000 cm(2) V(-1) s(-1)) found in any topological material. Direct evidence from transport, the unprecedentedly large diamagnetic screening, and the presence of ~25 meV gaps detected by scanning tunnelling spectroscopy reveal the superconducting condensate to emerge first in surface puddles, with the onset of global phase coherence at ~9 K. The rich structure of this state lends itself to manipulation via growth conditions and the material parameters such as Fermi velocity and mean free path. PMID- 26359208 TI - Chemotherapy increases long-term survival in patients with adult medulloblastoma- a literature-based meta-analysis. AB - BACKGROUND: Adult medulloblastoma is a potentially curable malignant entity with an incidence of 0.5-1 per million. Valid data on prognosis, treatment, and demographics are lacking, as most current knowledge stems from retrospective studies. Surgical resection followed by radiotherapy are accepted parts of treatment regimes; however, established prognostic factors and data clarifying the role of chemotherapy are missing. METHODS: We investigated 227 publications from 1969-2013, with 907 identifiable, individual patients being available for meta-analysis. Demographic data, risk stratification, and treatment of these patients were similar to previous cohorts. RESULTS: The median overall survival (mOS) was 65 months (95% CI: 54.6-75.3) , the 5-year overall survival was 50.9% with 16% of the patients dying more than 5 years after diagnosis. Incomplete resection, clinical and radiological signs for brainstem infiltration, and abstinence from radiotherapy were predictive of worse outcome. Metastatic disease at tumor recurrence was identified as a new prognostic factor, while neither metastasis at initial diagnosis nor desmoplastic/classic histology was correlated with survival. Patients receiving chemotherapy first-line survived significantly longer (mOS: 108 mo, 95% CI: 68.6-148.4) than patients treated with radiation alone (mOS: 57 mo, 95% CI: 39.6-74.4) or patients who received chemotherapy at tumor recurrence. This effect was not biased by tumor stage or decade of treatment. Importantly, (neo)adjuvant chemotherapy also significantly increased the chance for long-term survival (>5 y) compared with radiotherapy alone or chemotherapy at tumor recurrence. CONCLUSIONS: This meta-analysis clarifies relevant prognostic factors and suggests that chemotherapy as part of first-line therapy improves overall survival and increases the proportion of patients with long-term survival. PMID- 26359210 TI - How neuronal activity regulates glioma cell proliferation. PMID- 26359209 TI - Strategies to improve delivery of anticancer drugs across the blood-brain barrier to treat glioblastoma. AB - Glioblastoma (GBM) is a lethal and aggressive brain tumor that is resistant to conventional radiation and cytotoxic chemotherapies. Molecularly targeted agents hold great promise in treating these genetically heterogeneous tumors, yet have produced disappointing results. One reason for the clinical failure of these novel therapies can be the inability of the drugs to achieve effective concentrations in the invasive regions beyond the bulk tumor. In this review, we describe the influence of the blood-brain barrier on the distribution of anticancer drugs to both the tumor core and infiltrative regions of GBM. We further describe potential strategies to overcome these drug delivery limitations. Understanding the key factors that limit drug delivery into brain tumors will guide future development of approaches for enhanced delivery of effective drugs to GBM. PMID- 26359211 TI - Dynamic Transcriptional Regulation of Fis in Salmonella During the Exponential Phase. AB - Fis is one of the most important global regulators and has attracted extensive research attention. Many studies have focused on comparing the Fis global regulatory networks for exploring Fis function during different growth stages, such as the exponential and stationary stages. Although the Fis protein in bacteria is mainly expressed in the exponential phase, the dynamic transcriptional regulation of Fis during the exponential phase remains poorly understood. To address this question, we used RNA-seq technology to identify the Fis-regulated genes in the S. enterica serovar Typhimurium during the early exponential phase, and qRT-PCR was performed to validate the transcriptional data. A total of 1495 Fis-regulated genes were successfully identified, including 987 Fis-repressed genes and 508 Fis-activated genes. Comparing the results of this study with those of our previous study, we found that the transcriptional regulation of Fis was diverse during the early- and mid-exponential phases. The results also showed that the strong positive regulation of Fis on Salmonella pathogenicity island genes in the mid-exponential phase transitioned into insignificant effect in the early exponential phase. To validate these results, we performed a cell infection assay and found that Deltafis only exhibited a 1.49 fold decreased capacity compared with the LT2 wild-type strain, indicating a large difference from the 6.31-fold decrease observed in the mid-exponential phase. Our results provide strong evidence for a need to thoroughly understand the dynamic transcriptional regulation of Fis in Salmonella during the exponential phase. PMID- 26359212 TI - Monolayered Bi2WO6 nanosheets mimicking heterojunction interface with open surfaces for photocatalysis. AB - Two-dimensional-layered heterojunctions have attracted extensive interest recently due to their exciting behaviours in electronic/optoelectronic devices as well as solar energy conversion systems. However, layered heterojunction materials, especially those made by stacking different monolayers together by strong chemical bonds rather than by weak van der Waal interactions, are still challenging to fabricate. Here the monolayer Bi2WO6 with a sandwich substructure of [BiO](+)-[WO4](2-)-[BiO](+) is reported. This material may be characterized as a layered heterojunction with different monolayer oxides held together by chemical bonds. Coordinatively unsaturated Bi atoms are present as active sites on the surface. On irradiation, holes are generated directly on the active surface layer and electrons in the middle layer, which leads to the outstanding performances of the monolayer material in solar energy conversion. Our work provides a general bottom-up route for designing and preparing novel monolayer materials with ultrafast charge separation and active surface. PMID- 26359213 TI - Focused post mortem dissection technique for harvest of rete mirabile in domestic swine (Sus scrofa). AB - BACKGROUND: Rete mirabile (RM) of the domestic pig is a popular animal model of arteriovenous malformations. The RM (Latin for 'wonderful net)' comprises the arterioarterial portal connecting ascending pharyngeal arteries and the internal carotid arteries, which exists in the skull base of even-toed ungulates. Although angiographic access of the RM is relatively easy, its post mortem procurement is complicated and its detailed technique has not been well described. OBJECTIVE: To present our focused post mortem dissection technique for undamaged and complete harvest of the RM. MATERIALS AND METHODS: Fourteen domestic (40-70 lb (18-32 kg)) swine were used in this study. Angiographies were performed under general anesthesia in all animals. A 5F Berenstein catheter was used for angiography and a 014 microcatheter was used to obtain superselective angiography. A stepwise surgical dissection technique has been developed to efficiently harvest RM. Angiographic and surgical anatomy were also compared. RESULTS: The RM was supplied by bilateral ascending pharyngeal arteries. Bilateral anterior cerebral arteries, middle cerebral arteries, and the basilar system were identified rostral to the RM. Our surgical dissection technique was developed during a project to streamline harvesting of the RM and a stepwise description is as follows: (1) decapitate the swine by removing the head through the plane of the occiput and C1 vertebral body; (2) remove the tongue and oropharynx via a ventral approach; (3) dissect through the posterior pharyngeal wall identifying bilateral tympanic bullae and the basisphenoid bone; and (4) remove the basisphenoid bone about one and half inches above the rostral end of the tympanic bullae to fully expose the rete. CONCLUSIONS: The RM can be procured efficiently and effectively with our technique, without requiring any sophisticated surgical devices. PMID- 26359214 TI - Bioactive versus bare platinum coils for the endovascular treatment of intracranial aneurysms: systematic review and meta-analysis of randomized clinical trials. AB - BACKGROUND: Bioactive coils were introduced in 2002 in an attempt to improve aneurysm healing and durability of angiographic results. Evidence demonstrating superior efficacy to justify the routine use of bioactive coils over bare coils is limited. We compared the periprocedural and clinical outcome after bioactive and bare platinum coiling for intracranial aneurysms. METHODS: MEDLINE, EMBASE, Cochrane Library, and ISI Web of Knowledge Conference Proceedings Citation Index Science were searched for randomized clinical trials (RCTs) comparing bioactive and bare coils. The methodological quality was evaluated to assess bias risk. Periprocedural outcomes and mid-term outcomes were compared. RESULTS: Five independent RCTs comparing bioactive (n=1084) and bare coils (n=1084) were identified. Periprocedural outcome was similar for both groups. Bioactive coiling increased the rate of complete aneurysm occlusion (47% vs 40%; RR 1.17 (95% CI 1.05 to 1.31); p=0.006) and reduced the rate of residual aneurysm neck at 10 months compared with bare coiling in the mid-term (26% vs 31%; RR 0.82 (95% CI 0.70 to 0.96); p=0.01). There were no differences in aneurysm recurrence, aneurysm rupture, stroke, neurological death, modified Rankin Scale score and reinterventions. Subgroup analysis for the three RCTs on hydrogel coils demonstrated reduction of residual aneurysms compared with bare coiling (25% vs 34%; RR 0.76 (95% CI 0.58 to 0.99); p=0.04). CONCLUSIONS: Bioactive coils ensure a higher rate of medium-term complete aneurysm occlusion while reducing the rate of residual neck aneurysms compared with bare coiling in the mid-term. Hydrogel coils reduce residual aneurysms compared with bare coils. While there is level 1a evidence to show more complete aneurysm occlusion, longer term follow-up is needed to determine if this translates into clinical significance. PMID- 26359215 TI - Potential role of folate in pre-eclampsia. AB - Dietary deficiencies of folate and other B vitamin cofactors involved in one carbon metabolism, together with genetic polymorphisms in key folate-methionine metabolic pathway enzymes, are associated with increases in circulating plasma homocysteine, reduction in DNA methylation patterns, and genome instability events. All of these biomarkers have also been associated with pre-eclampsia. The aim of this review was to explore the literature and identify potential knowledge gaps in relation to the role of folate at the genomic level in either the etiology or the prevention of pre-eclampsia. A systematic search strategy was designed to identify citations in electronic databases for the following terms: folic acid supplementation AND pre-eclampsia, folic acid supplementation AND genome stability, folate AND genome stability AND pre-eclampsia, folic acid supplementation AND DNA methylation, and folate AND DNA methylation AND pre eclampsia. Forty-three articles were selected according to predefined selection criteria. The studies included in the present review were not homogeneous, which made pooled analysis of the data very difficult. The present review highlights associations between folate deficiency and certain biomarkers observed in various tissues of women at risk of pre-eclampsia. Further investigation is required to understand the role of folate in either the etiology or the prevention of pre eclampsia. PMID- 26359216 TI - Nanoparticle distribution during systemic inflammation is size-dependent and organ-specific. AB - This study comprehensively investigates the changing biodistribution of fluorescent-labelled polystyrene latex bead nanoparticles in a mouse model of inflammation. Since inflammation alters systemic circulatory properties, increases vessel permeability and modulates the immune system, we theorised that systemic inflammation would alter nanoparticle distribution within the body. This has implications for prospective nanocarrier-based therapies targeting inflammatory diseases. Low dose lipopolysaccharide (LPS), a bacterial endotoxin, was used to induce an inflammatory response, and 20 nm, 100 nm or 500 nm polystyrene nanoparticles were administered after 16 hours. HPLC analysis was used to accurately quantify nanoparticle retention by each vital organ, and tissue sections revealed the precise locations of nanoparticle deposition within key tissues. During inflammation, nanoparticles of all sizes redistributed, particularly to the marginal zones of the spleen. We found that LPS-induced inflammation induces splenic macrophage polarisation and alters leukocyte uptake of nanoparticles, with size-dependent effects. In addition, spleen vasculature becomes significantly more permeable following LPS treatment. We conclude that systemic inflammation affects nanoparticle distribution by multiple mechanisms, in a size dependent manner. PMID- 26359217 TI - The clinical safety of ibrutinib in chronic lymphocytic leukemia. AB - INTRODUCTION: Ibrutinib , a targeted inhibitor of B-cell receptor signaling, achieved impressive clinical results for patients with chronic lymphocytic leukemia (CLL). These results allowed the approval of ibrutinib for the treatment of patients with CLL who have received at least one prior therapy and those with a 17p deletion regardless of line of therapy. AREAS COVERED: Comprehensive data from either Phase I-II or randomized Phase III studies are analyzed in this article. In addition, we reviewed data on the prevalence and the clinical management of some peculiar toxicities ibrutinib related such as lymphocytosis, major bleeding and atrial fibrillation. EXPERT OPINION: Ibrutinib has radically changed the scenery of relapsed/refractory CLL treatment and established an important paradigm in the molecularly targeted approach of this disease. Discontinuation of ibrutinib is rarely due to adverse events related to the drug. Patients who discontinue treatment represent a challenge to the physicians because treatment options are very limited. PMID- 26359218 TI - Enzyme-instructed self-assembly of taxol promotes axonal branching. AB - Axonal branching is important for vertebrate neuron signaling. Taxol has a biphasic effect on axonal branching (i.e., high concentration inhibits axonal growth but low concentration restores it). To the best of our knowledge, low concentration of taxol to promote axonal branching has not been reported yet. Herein, we rationally designed a taxol derivative Fmoc-Phe-Phe-Lys(taxol) Tyr(H2PO4)-OH (1) which could be subjected to alkaline phosphatase (ALP) catalyzed self-assembly to form taxol nanofibers. We found that, at 10 MUM, 1 has a microtubule (MT) condensation effect similar to that of taxol on mammalian cells but with more chronic toxicity than taxol on the cells. At a low concentration of 10 nM, 1 not only promoted neurite elongation as taxol did but also promoted axonal branching which was not achieved by using taxol. We propose that self-assembly of 1 along the MTs prohibited their lateral contacts and thus promoted axonal branching. Our strategy of enzyme-instructed self-assembly (EISA) of a taxol derivative provides a new tool for scientists to study the morphology of neurons, as well as their behaviours. PMID- 26359219 TI - Safety and tolerability of anticonvulsant medication in bipolar disorder. AB - INTRODUCTION: Anticonvulsants (AC) are widely used and recommended as a treatment option in different phases of bipolar disorder (BD). In contrast to ample evidence for efficacy in acute mania, there is generally less unambiguous evidence for maintenance treatment or bipolar depression, and data on long-term tolerability in BD are sparse, although this varies greatly between different compounds. This review summarizes the clinically relevant tolerability and safety profile of ACs commonly used for the treatment of BD based on findings from randomized controlled trials (RCT). AREAS COVERED: Systematic search of the English literature between January 1991 and May 2015 revealed a total of nine RCTs investigating valproate, five RCTs with carbamazepine and 8 with lamotrigine For these ACs we found information on side effect profiles for both acute and maintenance RCTs, albeit of varying quality, whereas for topiramate (five RCTs), gabapentin and esclicarbazepine acetate (one RCT each) only acute treatment RCTs have been published. Descriptive side effect profiles from open-label studies exist for several other ACs rarely used in BD, and are included in this review as a brief narrative chapter. EXPERT OPINION: Whereas both valproate and carbamazepine are associated with, in part, severe adverse events, lamotrigine emerges as a relatively safe and well tolerated treatment option, especially in maintenance treatment and prevention of depressive relapse in BD. Lack of proven efficacy and side effect profile of other, less rigorously studied ACs restricts their use only to very selected BD cases. PMID- 26359220 TI - Effect evaluation of a self-management programme for employees with complaints of the arm, neck or shoulder: a randomised controlled trial. AB - OBJECTIVE: To evaluate the effectiveness of a self-management intervention (including an eHealth module), compared with usual care, in employees with chronic non-specific complaints of the arm, neck or shoulder (persisting >3 months). METHODS: Participants were randomised into the self-management group (SG) or usual care group (UCG). The SG participated in 6 self-management sessions and could use an eHealth module; the UCG could use all available usual care. The primary outcome of the study was score on the Disabilities of the Arm, Shoulder and Hand questionnaire (DASH). Secondary outcomes included: absenteeism, pain in the previous week, quality of life, pain catastrophising, self-efficacy, work style, presenteeism, fatigue, and limitations experienced during work. Data were analysed using generalised estimating equations (GEE) linear regression and Mann Whitney U tests, and were collected at baseline, 3-month, 6-month, and 12-month follow-up. RESULTS: On the general module of the DASH, no significant difference between SG and the UCG was detected. On most of the other outcome measures, there were no significant between-group differences. In the DASH work module, the between-group effect was -3.82 (95% CI -7.46 to -0.19, p=0.04). For limitations experienced in job-related activities the between-group effect was -1.01 (95% CI 1.97 to -0.04, p=0.04). The mean hours of sport activities in the past 3 months, measured at 12 months, was 1.00 h (95% CI -1.90 to -0.12 h, p=0.03) less in the SG compared with the UCG. CONCLUSIONS: The self-management intervention improved the participants' perceived disability during work. Since no significant between group differences were found on most outcome measures, the results of this study should be interpreted with caution. TRIAL REGISTRATION NUMBER: Dutch Trial Registration number NTR 3816. PMID- 26359221 TI - Metformin: risk-benefit profile with a focus on cancer. AB - INTRODUCTION: Epidemiological evidence suggests an increased incidence of cancer in obese, prediabetic, and diabetic patients and a reduced risk of cancer incidence and mortality in diabetic patients on metformin compared with other antidiabetic drugs. In vitro studies support the efficacy of metformin in cancer therapy and prevention. Although metformin seems to be promising as a cancer chemopreventive or therapeutic drug, the principal consideration is whether metformin will be effective in cancer clinical trials for nondiabetic subjects or only in diabetics or subjects with insulin resistance. Safety of metformin is even more important in treating nondiabetic patients. AREAS COVERED: The present review focuses on epidemiological data and clinical trials testing the efficacy of metformin on cancer, the safety in nondiabetic patients and the future development of this promising drug. EXPERT OPINION: Meta-analyses of epidemiological in which metformin treatment has been used for diabetic patients show a positive trend for benefit; nevertheless, clinical data outcomes are preliminary and the results of ongoing trials are awaited. The different types of cancer, heterogeneity of populations and presence of comorbidity make it difficult to determine the benefits of metformin in cancer prevention and treatment. PMID- 26359222 TI - Experimental and investigational therapies for chemotherapy-induced anemia. AB - INTRODUCTION: In cancer patients, anemia is frequently observed, particularly as a consequence to chemotherapy (chemotherapy-induced anemia, CIA). CIA is treated with Red Blood Cell transfusions and erythropoiesis-stimulating agents (ESAs). However, the use of ESAs in anemic cancer patients is associated with reduced survival time and time to progression. Consequently, new therapeutic options are needed. AREAS COVERED: In this article, the authors discuss new erythroid enhancing agents (EEAs) that act differently to erythropoietin. Specifically, the article summarizes the early clinical development of activin antagonists (Sotatercep [ACE-011] and ACE-536) and hepcidin antagonists [NOX-H94]). EXPERT OPINION: Both Activin RIIA trap agents and hepcidin inhibitors are promising new EEAs, but their safety profile, and their impact on treating CIA, needs to be carefully assessed in controlled clinical trials over longer periods of time. It is also important to carefully evaluate CIA patients to properly assess the physiopathological mechanisms responsible for the development of their anemic condition and provide patients with the most appropriate treatment plan. PMID- 26359223 TI - Emerging drugs for overactive bladder. AB - INTRODUCTION: Overactive bladder (OAB) is a common problem which can have disastrous effects on the quality of life of the sufferer. There are established treatments for the problem but they have significant adverse effects. Better drugs and new treatment modalities are necessary to deal with OAB. AREA COVERED: Antimuscarinics, mirabegron and intravesical injection of botulinum toxin A are established treatments for OAB. Sacral neuromodulation is more invasive but has been successful in treating OAB. Phase II and III trials are in progress for newer beta3-agonists and various combinations of antimuscarinics, beta3-agonists and antidiuretics. Targeted secretion inhibitors (TSI) can increase efficacy and reduce adverse effects. Liposome integrated botulinum toxin A has an advantage of effective administration by intravesical instillation. Both medicines are in Phase II trials. Many other drugs which have promising results are discussed. EXPERT OPINION: Newer antimuscarinics have better tolerability. Long-term data for mirabegron has shown that it is more effective in severe OAB. Combination drugs may prove to be more effective with less adverse effects. Emerging treatments with TSI, lipotoxin and gene therapy appear promising. PMID- 26359224 TI - Advancing pharmacological treatment options for advanced gastric cancer. AB - INTRODUCTION: Gastric cancer is the third most common cause of cancer-related deaths worldwide. Improvement of conventional chemotherapy has been modest in the past decades. AREAS COVERED: We review recent important studies of metastatic or recurrent gastric cancer. For human epidermal growth factor receptors 2 (HER2) negative cancer, standard treatments are combinations of fluoropyrimidine and platinum with or without epirubicin or docetaxel in first-line therapy. Controversy exists regarding the use of triplet chemotherapies due to their toxicity. For HER2 positive cancer, standard treatments are combinations of fluoropyrimidine and cisplatin with trastuzumab. As second- or third-line treatment, taxanes or irinotecan prolonged survival compared with best supportive care alone, but the extension of overall survival was only 1 - 2 months. A recent study demonstrated that ramucirumab plus paclitaxel improved survival as a second line therapy. EXPERT OPINION: Most trials have failed to demonstrate a benefit of targeted agents. It is important to identify predictive biomarkers to enrich an appropriate patient population for targeted agents such as HER2 status for trastuzumab. PMID- 26359225 TI - Polymorphisms of human 8-oxoguanine DNA glycosylase 1 and 8-hydroxydeoxyguanosine increase susceptibility to arsenic methylation capacity-related urothelial carcinoma. AB - Arsenic causes oxidative stress in cultured animal and human cells, and it is a well-documented human carcinogen. We conducted a hospital-based case-control study including 167 cases of urothelial carcinoma (UC) and 334 age- and gender matched healthy controls to evaluate the relationships between urinary arsenic profiles, urinary 8-hydroxydeoxyguanosine (8-OHdG) levels, and human 8-oxoguanine DNA glycosylase (hOGG1) genotypes and UC. The urinary arsenic species were analyzed by high-performance liquid chromatography and hydride generator-atomic absorption spectrometry. Genotyping for hOGG1 (Ser326Cys) and hOGG1 (-15C>G) was performed using the Sequenom MassARRAY platform with iPLEX Gold chemistry. Urinary 8-OHdG was measured with high-sensitivity enzyme-linked immunosorbent assay kits. The results indicated that the hOGG1 326 Cys/Cys genotype and the hOGG1 -15C>G G/G genotype were associated with an increased risk of UC (OR [95 % CI] 1.57 [1.04-2.35] and 1.57 [1.04-2.35], respectively). Participants with high urinary total arsenic, regardless of the haplotype of hOGG1 Ser326Cys and the 15C>G polymorphism, had significantly higher urinary 8-OHdG compared to participants with low urinary total arsenic. This is the first study to investigate the joint effects of high urinary total arsenic or inefficient arsenic methylation capacity indices, and the high-risk G-G haplotype of hOGG1 on the risk of UC. The findings are especially meaningful for participants with risk factors such as high urinary total arsenic, inefficient arsenic methylation indices, high urinary 8-OHdG, and the high-risk G-G haplotype of hOGG1 which are all associated with an increased UC risk. PMID- 26359226 TI - Effects of D- and L-govadine on the disruption of touchscreen object-location paired associates learning in rats by acute MK-801 treatment. AB - RATIONALE: New pharmacological treatments for the cognitive deficits in schizophrenia are needed. Tetrahydroprotoberberines, such as govadine, are one class of compounds with dopaminergic activities that may be useful in treating some aspects of the cognitive symptoms of the disorder. OBJECTIVE: The objective of the present studies was to test the effects of the D- and L-enantiomers of govadine on the impairment in a paired-associate learning (PAL) task produced by acute MK-801 in rats. We also assessed effects of the typical antipsychotic haloperidol as a comparator compound. METHODS: MK-801 (0.05, 0.1, 0.15, and 0.2 mg/kg), D- and L-govadine (0.3, 1.0, and 3.0 mg/kg), and haloperidol (0.05, 0.1, and 0.25 mg/kg) were administered acutely to rats well trained on the PAL task in touchscreen-equipped operant conditioning chambers. RESULTS: Acute MK-801 impaired performance of PAL in a dose-dependent manner by reducing accuracy and increasing correction trials. L-Govadine (1.0 mg/kg), but not D-govadine, blocked the disruptive effects of MK-801 (0.15 mg/kg) on PAL. Haloperidol failed to affect the MK-801-induced disruption of PAL. Higher doses of L-govadine and haloperidol dramatically impaired performance of the task which confounded interpretation of cognitive outcomes. CONCLUSION: L-Govadine appears unique in its ability to improve performance of the MK-801-induced impairment in the PAL task. This behavioral effect may relate the ability of L-govadine to antagonize dopamine D2 receptors while also promoting dopamine efflux. Future research should further characterize the role of the dopamine system in the rodent PAL task to elucidate the mechanisms of its pro-cognitive effects. PMID- 26359227 TI - Effects of cholinesterase inhibitor on brain activation in Alzheimer's patients measured with functional near-infrared spectroscopy. AB - RATIONALE: Neurobiological effects of neuropsychiatric medication can contribute to the understanding of mechanisms of action and to the evaluation of target medication effects. Cholinesterase inhibitors (ChEI) have been used in patients with Alzheimer's disease (AD) for years with only small knowledge about the underlying neurobiological effects. The measurement of brain activation links neurobiological and functional aspects but is challenging in the group of demented patients; here, an alternative method, functional near-infrared spectroscopy (fNIRS), is introduced to measure those medication effects. OBJECTIVES: The current study investigated the influence of ChEI on cortical activation of patients with AD measured using fNIRS during a verbal fluency task (VFT). METHODS: In this study, 24 probable AD patients were investigated three times using fNIRS: before medication with rivastigmine was given (t0), when the medication was at the target dose after 4 weeks (t1), and after the target dose was kept constant for a further 8 weeks (t2). RESULTS: The results show a concentration increase of oxygenated hemoglobin as measured with fNIRS from t0 to t2 in speech relevant areas and a general decrease in prefrontal areas. Behaviorally, an improvement was found for the VFT used to measure cortical activation during fNIRS. In the neuropsychological test battery, no significant changes were found, yet high effect sizes for the mini mental status examination, immediate and delayed word list recall were found. CONCLUSIONS: The results indicate a positive effect of ChEI on cognitive function. The underlying cortical changes can be imaged using fNIRS. PMID- 26359228 TI - Possible role of the dopamine D1 receptor in the sensorimotor gating deficits induced by high-fat diet. AB - RATIONALE: High-fat diet (HFD) has been recently reported to induce sensorimotor gating deficits, but the underlying mechanisms are not well understood. OBJECTIVE: The purpose of this study is to determine whether HFD induces long lasting deficits in sensorimotor gating and to examine the involvement of altered dopamine (DA) function. METHODS: C57BL/6J mice were fed HFD for 10 weeks and then normal diet (ND) for 4 weeks. DA D2 receptor (D2R) knockout (KO) mice were also fed HFD for 10 weeks. The mice were evaluated for prepulse inhibition (PPI) of acoustic startle after HFD and the subsequent 4-week ND. We evaluated the effect of SCH23390, a D1 receptor (D1R) antagonist, on PPI and measured protein expression levels of D1R and D2R in the prefrontal cortex (PFC) in HFD mice. The concentrations of monoamines and their metabolites in the cortices of 10-week HFD or ND mice were measured using high performance liquid chromatography. RESULTS: Long-term HFD-induced PPI disruption in WT and D2R KO mice. Even after 4 weeks of subsequent ND, PPI remained to be disrupted. SCH23390 mitigated the PPI disruption. In HFD animals, D1R protein expression in the PFC was significantly decreased, while DA, homovanillic acid, and 3,4-dihydroxyphenylacetic acid levels in the cortex were increased. CONCLUSION: This is the first evidence that HFD can induce long-lasting deficits in sensorimotor gating through alteration of cortical levels of DA and its metabolites. Our data suggest that HFD-induced PPI deficits are related to altered D1R signaling and that D1R antagonists may have therapeutic effects on the deficits. PMID- 26359229 TI - Modulation of cyclins and p53 in mesangial cell proliferation and apoptosis during Habu nephritis. AB - BACKGROUND: Mesangial cell (MC) proliferation and apoptosis are the main pathological changes observed in mesangial proliferative nephritis. In this study, we explored the role of cyclins and p53 in modulating MC proliferation and apoptosis in a mouse model of Habu nephritis. METHODS: The Habu nephritis group was prepared by injection of Habu toxin. Mesangiolysis and mesangial expansion were determined by periodic acid-Schiff (PAS) reagent staining. Immunohistochemical analysis of PCNA and KI67, and TUNEL staining were used to detect cell proliferation and apoptosis, respectively. Expression levels of cyclins and p53 were examined by Western blotting. RESULTS: PAS staining showed that mesangial dissolution appeared on days 1 and 3, and mesangial proliferation with extracellular matrix accumulation was apparent by days 7 and 14. Both PCNA and KI67 immunohistochemical analysis showed that MC proliferation began on day 3, peaked on day 3 and 7, and recovered by day 14. TUNEL staining results showed that MC apoptosis began to increase on day 1, continued to rise on day 7, and peaked on day 14. Western blot analysis showed that cyclin D1 was upregulated on day 1, cyclins A2 and E were upregulated on days 3 and 7, and p53 was upregulated on days 3, 7 and 14. There was no change in the expression levels of Bax or p21. CONCLUSION: We explored the tendency for MC proliferation and apoptosis during the process of Habu nephritis and found that cyclins and p53 may modulate the disease pathology. This will help us determine the molecular pathogenesis of MC proliferation and provide new targets for disease intervention. PMID- 26359230 TI - Level of mortality risk for babies born preterm or with a small weight for gestation in a tertiary hospital of Nepal. AB - BACKGROUND: Globally, 15 million babies were born prematurely in 2012, with 37.6 % of them in South Asia. About 32.4 million infants were born small for gestational age (SGA) in 2010, with more than half of these births occurring in South Asia. In Nepal, 14 % of babies were born preterm and 39.3 % were born SGA in 2010. We conducted a study in a tertiary hospital of Nepal to assess the level of risk for neonatal mortality among babies who were born prematurely and/or SGA. METHODS: This case-control study was completed over a 15-month period between July 2012 and September 2013. All neonatal deaths that occurred during the study period were included as cases and 20 % of women with live births were randomly selected as referents. Information on potential risk factors was taken from medical records and interviews with the women. Logistic regression analyses were conducted to determine the level of risk for neonatal mortality among babies born preterm and/or SGA. RESULTS: During this period, the hospital had an incidence of preterm birth and SGA of 8.1 and 37.5%, respectively. In the multivariate model, there was a 12-fold increased risk of neonatal death among preterm infants compared to term. Babies who were SGA had a 40 % higher risk of neonatal death compared to those who were not. Additionally, babies who were both preterm and SGA were 16 times more likely to die during the neonatal period. CONCLUSIONS: Our study showed that the risk of neonatal mortality was highest when the baby was born both preterm and SGA, followed by babies who were born preterm, and then by babies who were SGA in a tertiary hospital in Nepal. In tertiary care settings, the risk of mortality for babies who are born preterm and/or SGA can be reduced with low-cost interventions such as Kangaroo Mother Care or improved management of complications through special newborn care or neonatal intensive care units. The risk of death for babies who are born prematurely and/or SGA can thus be used as an indicator to monitor the quality of care for these babies in health facility settings. CLINICAL TRIAL REGISTRATION: ISRCTN97846009. PMID- 26359231 TI - Prepatterning of differentiation-driven nuclear lamin A/C-associated chromatin domains by GlcNAcylated histone H2B. AB - Dynamic interactions of nuclear lamins with chromatin through lamin-associated domains (LADs) contribute to spatial arrangement of the genome. Here, we provide evidence for prepatterning of differentiation-driven formation of lamin A/C LADs by domains of histone H2B modified on serine 112 by the nutrient sensor O-linked N-acetylglucosamine (H2BS112GlcNAc), which we term GADs. We demonstrate a two step process of lamin A/C LAD formation during in vitro adipogenesis, involving spreading of lamin A/C-chromatin interactions in the transition from progenitor cell proliferation to cell-cycle arrest, and genome-scale redistribution of these interactions through a process of LAD exchange within hours of adipogenic induction. Lamin A/C LADs are found both in active and repressive chromatin contexts that can be influenced by cell differentiation status. De novo formation of adipogenic lamin A/C LADs occurs nonrandomly on GADs, which consist of megabase-size intergenic and repressive chromatin domains. Accordingly, whereas predifferentiation lamin A/C LADs are gene-rich, post-differentiation LADs harbor repressive features reminiscent of lamin B1 LADs. Release of lamin A/C from genes directly involved in glycolysis concurs with their transcriptional up-regulation after adipogenic induction, and with downstream elevations in H2BS112GlcNAc levels and O-GlcNAc cycling. Our results unveil an epigenetic prepatterning of adipogenic LADs by GADs, suggesting a coupling of developmentally regulated lamin A/C-genome interactions to a metabolically sensitive chromatin modification. PMID- 26359232 TI - Replication timing is regulated by the number of MCMs loaded at origins. AB - Replication timing is a crucial aspect of genome regulation that is strongly correlated with chromatin structure, gene expression, DNA repair, and genome evolution. Replication timing is determined by the timing of replication origin firing, which involves activation of MCM helicase complexes loaded at replication origins. Nonetheless, how the timing of such origin firing is regulated remains mysterious. Here, we show that the number of MCMs loaded at origins regulates replication timing. We show for the first time in vivo that multiple MCMs are loaded at origins. Because early origins have more MCMs loaded, they are, on average, more likely to fire early in S phase. Our results provide a mechanistic explanation for the observed heterogeneity in origin firing and help to explain how defined replication timing profiles emerge from stochastic origin firing. These results establish a framework in which further mechanistic studies on replication timing, such as the strong effect of heterochromatin, can be pursued. PMID- 26359234 TI - 25-Hydroxyvitamin D isomerizes to pre-25-hydroxyvitamin D in solution: considerations for calibration in clinical measurements. AB - Reference standards for the vitamin D metabolites 25-hydroxyvitamin D3, 25 hydroxyvitamin D2, and 3-epi-25-hydroxyvitamin D3 were evaluated using liquid chromatography (LC) with ultraviolet (UV) absorbance and mass spectrometric (MS) detection to assess purity. The chromatograms for solutions of all three 25(OH)D compounds, obtained using a pentafluorophenyl (PFP) stationary phase, revealed peaks that increased in area over time and had MS spectra that were nearly identical to the parent compound, indicating isomers had formed in solution that were unrelated to the reference standard purity. However, when the purity evaluations were completed with a cyanopropyl stationary phase, the isomeric products coeluted with the parent compounds and were not observable. The rates of formation of the isomeric products were found to increase when heated and were confirmed to be pre-25-hydroxyvitamin D compounds using spectral information from both MS detection and nuclear magnetic resonance (NMR) spectroscopy. The rates of conversion of 25(OH)D3 to pre-25(OH)D3 was studied in solutions of ethanol and bovine serum albumin (BSA) in phosphate-buffered saline (PBS). The solutions prepared with BSA/PBS were found to form twice as much pre-25(OH)D3 as the solutions in ethanol. The isomerization of 25(OH)D in solution has implications for calibration of 25(OH)D in clinical measurements, which are discussed. PMID- 26359233 TI - SORBS2 transcription is activated by telomere position effect-over long distance upon telomere shortening in muscle cells from patients with facioscapulohumeral dystrophy. AB - DNA is organized into complex three-dimensional chromatin structures, but how this spatial organization regulates gene expression remains a central question. These DNA/chromatin looping structures can range in size from 10-20 kb (enhancers/repressors) to many megabases during intra- and inter-chromosomal interactions. Recently, the influence of telomere length on chromatin organization prior to senescence has revealed the existence of long-distance chromatin loops that dictate the expression of genes located up to 10 Mb from the telomeres (Telomere Position Effect-Over Long Distances [TPE-OLD]). Here, we demonstrate the existence of a telomere loop at the 4q35 locus involving the sorbin and SH3 domain-containing protein 2 gene, SORBS2, a skeletal muscle protein using a modification of the chromosome conformation capture method. The loop reveals a cis-acting mechanism modifying SORBS2 transcription. The expression of this gene is altered by TPE-OLD in myoblasts from patients affected with the age-associated genetic disease, facioscapulohumeral muscular dystrophy (FSHD1A, MIM 158900). SORBS2 is expressed in FSHD myoblasts with short telomeres, while not detectable in FSHD myoblasts with long telomeres or in healthy myoblasts regardless of telomere length. This indicates that TPE-OLD may modify the regulation of the 4q35 locus in a pathogenic context. Upon differentiation, both FSHD and healthy myotubes express SORBS2, suggesting that SORBS2 is normally up-regulated by maturation/differentiation of skeletal muscle and is misregulated by TPE-OLD-dependent variegation in FSHD myoblasts. These findings provide additional insights for the complexity and age-related symptoms of FSHD. PMID- 26359235 TI - Hierarchical nanostructured noble metal/metal oxide/graphene-coated carbon fiber: in situ electrochemical synthesis and use as microelectrode for real-time molecular detection of cancer cells. AB - We report the design and fabrication of a new type of nanohybrid microelectrode based on a hierarchical nanostructured Au/MnO2/graphene-modified carbon fiber (CF) via in situ electrochemical synthesis, which leads to better structural integration of different building blocks into the CF microelectrode. Our finding demonstrates that wrapping CF with graphene nanosheets has dramatically increased the surface area and electrical conductivity of the CF microelectrode. The subsequent template-free electrodeposition of MnO2 on graphene-wrapped CF gives rise to a porous nanonest architecture built up from twisted and intersectant MnO2 nanowires, which serves as an ideal substrate for the direct growth of Au nanoparticles. Owing to the structural merit and synergy effect between different components, the hierarchical nanostructured noble metal/metal oxide/graphene coated CF demonstrates dramatically enhanced electrocatalytic activity. When used for nonenzymatic H2O2 sensing, the resultant modified microelectrode exhibits acceptable sensitivity, reproducibility, stability, and selectivity, which enable it to be used for real-time tracking H2O2 secretion in human cervical cancer cells. Graphical abstract A schematic illustration of preparation of hierarchical Au/MnO2/ERGO/CF nanohybrid electrode for real-time molecular detection of cancer cells. PMID- 26359236 TI - Effects of prostaglandin E1 on callus formation in rabbits. AB - BACKGROUND: Recent research has focused on identifying chemical modulators of osteogenesis. We present initial findings on the osteoinductive properties of prostaglandin E1 (Vasaprostan), using a rabbit model. METHODS: Data were collected on callus formation in 14 male rabbits. These were divided into two groups (control and treatment) with 7 animals in each group. In all animals, the right tibia was fractured using a standardized protocol and stabilized by an intramedullary nail. Treatment group received a 5 MUg/kg subcutaneous injection of PGE1/day during 10 postoperative days. Visual and radiological evaluation of callus formation was prospectively collected. After 30 days, all animals were killed and the tibia specimens were examined histologically. RESULTS: In all the treatment group animals, fractures were consolidated radiologically by day 30. No treatment group animals and two control group animals were excluded form the experiment. In the control group, 4 animals demonstrated slower callus formation than the main group. Two control group animals were excluded from the experiment on the 20th day due to wound infection; one developed a nonunion. The mean coefficient of bone callus thickening in the main group was 2.08 (+/-0, 16) and 1.77 (+/-0.05) (p < 0.05) in the control group. Calculation of mean quantity of neogenic vessels in 10 random visual fields of the bone callus revealed 78 (+/ 9.82) in the main group and 40 (+/-4.68) in the control group (p < 0.05). CONCLUSIONS: Our study demonstrates an increased rate and amount of bone callus formation in the group treated with prostaglandin E1 compared to the control group. Prospective radiological analysis was corroborated by histologic evaluation. PMID- 26359237 TI - Cavity averages for hard spheres in the presence of polydispersity and incomplete data. AB - We develop a cavity-based method which allows to extract thermodynamic properties from position information in hard-sphere/disk systems. So far, there are available-volume and free-volume methods. We add a third one, which we call available volume after take-out, and which is shown to be mathematically equivalent to the others. In applications, where data sets are finite, all three methods show limitations, and they do this in different parameter ranges. We illustrate the principal equivalence and the limitations on data from molecular dynamics: In particular, we test robustness against missing data. We have in mind experimental limitations where there is a small polydispersity, say 4% in the particle radii, but individual radii cannot be determined. We observe that, depending on the used method, the errors in such a situation are easily 100% for the pressure and 10kT for the chemical potentials. Our work is meant as guideline to the experimentalists for choosing the right one of the three methods, in order to keep the outcome of experimental data analysis meaningful. PMID- 26359238 TI - Exercise-induced metabolic fluctuations influence AMPK, p38-MAPK and CaMKII phosphorylation in human skeletal muscle. AB - During transition from rest to exercise, metabolic reaction rates increase substantially to sustain intracellular ATP use. These metabolic demands activate several kinases that initiate signal transduction pathways which modulate transcriptional regulation of mitochondrial biogenesis. The purpose of this study was to determine whether metabolic fluctuations per se affect the signaling cascades known to regulate peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha). On two separate occasions, nine men performed a continuous (30-min) and an intermittent exercise (30 * 1-min intervals separated by 1-min of recovery) at 70% of VO2peak. Skeletal muscle biopsies from the vastus lateralis were taken at rest and at +0 h and +3 h after each exercise. Metabolic fluctuations that correspond to exercise-induced variation in metabolic rates were determined by analysis of VO2 responses. During intermittent exercise metabolic fluctuations were 2.8-fold higher despite identical total work done to continuous exercise (317 +/- 41 vs. 312 +/- 56 kJ after intermittent and continuous exercise, respectively). Increased phosphorylation of AMP-activated protein kinase (AMPK) (~2.9-fold, P < 0.01), calcium/calmodulin-dependent protein kinase II (CaMKII) (~2.7-fold, P < 0.01) and p38-mitogen-activated protein kinase (MAPK) (~4.2-fold, P < 0.01) occurred immediately in both exercises and to a greater extent after the intermittent exercise (condition x time interaction, P < 0.05). A single bout of intermittent exercise induces a greater activation of these signaling pathways regulating PGC-1alpha when compared to a single bout of continuous exercise of matched work and intensity. Chronic adaptations to exercise on mitochondria biogenesis are yet to be investigated. PMID- 26359239 TI - Early myogenic responses to acute exercise before and after resistance training in young men. AB - To enable dynamic regulation of muscle mass and myofiber repair following injury, a satellite cell precursor population exists to supply additional nuclei. Activated satellite cells express many genes and associated proteins necessary for maturation and incorporation into the damaged fiber. There is little knowledge about the response of these markers following whole-body resistance exercise training. We investigated the impact of 12 weeks of progressive whole body resistance training on the expression of MRFs, PAX7, NCAM, and FA1, incorporating both acute and chronic resistance exercise components. Ten young recreationally active males (21.2 +/- 3.5 years) performed 12 weeks of whole-body resistance training at 70-85% of their predetermined one-repetition maximum (1RM). At the initiation and completion of the training period, muscular strength was assessed by RM and dynamometer testing, and vastus lateralis samples were obtained prior to and 3 h following an acute resistance exercise test (both whole body and isometric exercises). Increased mRNA expression of PAX7 (threefold), NCAM (threefold), MYF5 (threefold), MYOD (threefold) and MYOGENIN (twofold) was observed 3 h after the acute resistance exercise test, both pre and posttraining. Similarly, PAX7 (11-fold) and FA1 (twofold) protein abundance increased after acute exercise, while resting NCAM (eightfold) and FA1 (threefold) protein abundance increased following 12 weeks of resistance training. It is possible that these molecular changes are primarily due to the preceding exercise bout, and are not modified by long-term or whole-body exercise training. PMID- 26359240 TI - Regulation of nerve-evoked contractions of rabbit vas deferens by acetylcholine. AB - Stimulation of intramural nerves in the vas deferens of many species yields a classical biphasic contraction comprised of an initial fast component, mediated by P2X receptors and a second slower component, mediated by alpha1-adrenoceptors. It is also recognized that sympathetic nerve-mediated contractions of the vas deferens can be modulated by acetylcholine (Ach), however there is considerable disagreement in the literature regarding the precise contribution of cholinergic nerves to contraction of the vas deferens. In this study we examined the effect of cholinergic modulators on electric field stimulation (EFS)-evoked contractions of rabbit vas deferens and on cytosolic Ca(2+) levels in isolated vas deferens smooth muscle cells (VDSMC). The sustained component of EFS-evoked contractions was inhibited by atropine and by the selective M3R antagonist, 1,1-dimethyl-4 diphenylacetoxypiperidinium iodide (4-DAMP). EFS-evoked contractions were potentiated by Ach, carbachol (Cch), and neostigmine. The sustained phase of the EFS-evoked contraction was inhibited by prazosin, an alpha1-adrenoceptor antagonist and guanethidine, an inhibitor of noradrenaline release, even in the continued presence of Ach, Cch or neostigmine. The soluble guanylate cyclase (sGC) inhibitor, 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one enhanced the amplitude of EFS-evoked contractions and reduced the inhibitory effects of 4 DAMP. Isolated VDSMC displayed spontaneous Ca(2+) oscillations, but did not respond to Cch. However, the alpha1-adrenoceptor agonist, phenylephrine, evoked a Ca(2+) transient and contracted the cells. These data suggest that EFS-evoked contractions of the rabbit vas deferens are potentiated by activation of M3 receptors and reduced by activation of a sGC-dependent inhibitory pathway. PMID- 26359241 TI - Ginsenoside Rb1 increases insulin sensitivity by activating AMP-activated protein kinase in male rats. AB - Although ginseng has been reported to ameliorate hyperglycemia in animal models and clinical studies, the molecular mechanisms are largely unknown. We previously reported that chronic treatment with ginsenoside Rb1 (Rb1), a major component of ginseng, significantly reduced fasting glucose and improved glucose tolerance in high-fat diet (HFD)-induced obese rats. These effects were greater than those observed in pair-fed rats, suggesting a direct effect of Rb1 on glucose homeostasis, and this possibility was confirmed in the present study. In lean rats fed standard rodent chow, 5-day treatment with Rb1 significantly improved glucose tolerance and enhanced insulin sensitivity. Notably, those effects were not accompanied by reduced food intake or changed body weight. To elucidate the underlying molecular mechanisms, rats fed a HFD for 4 weeks were treated with Rb1 for 5 days. Subsequently, euglycemic-hyperinsulinemic clamp studies found that compared to vehicle, Rb1, while not changing food intake or body weight, significantly increased glucose infusion rate required to maintain euglycemia. Consistent with this, insulin-induced inhibition of hepatic gluconeogenesis was significantly enhanced and hepatic phosphoenolpyruvate carboxykinase and glucose 6-phosphatase gene expression was suppressed. Additionally, glucose uptake was significantly increased in skeletal muscle. While proximal insulin signaling was not changed after Rb1 treatment, increased phosphorylation of TBC1D4, a downstream target of AMPK signaling, appears to be a key part of the mechanism for Rb1-stimulated glucose uptake in skeletal muscle. These findings indicate that Rb1 has multiple effects on glucose homeostasis, and provide strong rationale for further evaluation of its potential therapeutic role. PMID- 26359242 TI - Unchained melody: revisiting the estimation of SF-6D values. AB - PURPOSE: In the original SF-6D valuation study, the analytical design inherited conventions that detrimentally affected its ability to predict values on a quality-adjusted life year (QALY) scale. Our objective is to estimate UK values for SF-6D states using the original data and multi-attribute utility (MAU) regression after addressing its limitations and to compare the revised SF-6D and EQ-5D value predictions. METHODS: Using the unaltered data (611 respondents, 3503 SG responses), the parameters of the original MAU model were re-estimated under three alternative error specifications, known as the instant, episodic, and angular random utility models. Value predictions on a QALY scale were compared to EQ-5D3L predictions using the 1996 Health Survey for England. RESULTS: Contrary to the original results, the revised SF-6D value predictions range below 0 QALYs (i.e., worse than death) and agree largely with EQ-5D predictions after adjusting for scale. Although a QALY is defined as a year in optimal health, the SF-6D sets a higher standard for optimal health than the EQ-5D-3L; therefore, it has larger units on a QALY scale by construction (20.9 % more). CONCLUSIONS: Much of the debate in health valuation has focused on differences between preference elicitation tasks, sampling, and instruments. After correcting errant econometric practices and adjusting for differences in QALY scale between the EQ-5D and SF-6D values, the revised predictions demonstrate convergent validity, making them more suitable for UK economic evaluations compared to original estimates. PMID- 26359243 TI - Switching insurer in the Irish voluntary health insurance market: determinants, incentives, and risk equalization. AB - BACKGROUND: The determinants of consumer mobility in voluntary health insurance markets providing duplicate cover are not well understood. Consumer mobility can have important implications for competition. Consumers should be price-responsive and be willing to switch insurer in search of the best-value products. Moreover, although theory suggests low-risk consumers are more likely to switch insurer, this process should not be driven by insurers looking to attract low risks. METHODS: This study utilizes data on 320,830 VHI healthcare policies due for renewal between August 2013 and June 2014. At the time of renewal, policyholders were categorized as either 'switchers' or 'stayers', and policy information was collected for the prior 12 months. Differences between these groups were assessed by means of logistic regression. The ability of Ireland's risk equalization scheme to account for the relative attractiveness of switchers was also examined. RESULTS: Policyholders were price sensitive (OR 1.052, p < 0.01), however, price sensitivity declined with age. Age (OR 0.971; p < 0.01) and hospital utilization (OR 0.977; p < 0.01) were both negatively associated with switching. In line with these findings, switchers were less costly than stayers for the 12 months prior to the switch/renew decision for single person (difference in average cost = ?540.64) and multiple-person policies (difference in average cost = ?450.74). Some cost differences remain for single-person policies following risk equalization (difference in average cost = ?88.12). CONCLUSIONS: Consumers appear price-responsive, which is important for competition provided it is based on correct incentives. Risk equalization payments largely eliminated the profitable status of switchers, although further refinements may be required. PMID- 26359245 TI - Pain, quality of life and activity in aged evacuees living in temporary housing after the Great East Japan earthquake of 11 March 2011: a cross-sectional study in Minamisoma City, Fukushima prefecture. AB - BACKGROUND: The aim of this study was to clarify pain, quality of life and activity in the aged evacuees living in temporary housing after the Great East Japan Earthquake on 11 March 2011. METHODS: The study was a cross-sectional study performed in Minamisoma City, Fukushima Prefecture 1 year and 6 months after the disaster. Inclusion criteria were the ability to walk independently and consent to answer questionnaires. Seventy-one evacuees who met the inclusion criteria were included in this study. There were 16 men and 55 women with a mean age of 75.9 years. Sixty evacuees were surveyed when they gathered at the assembly hall in the temporary housing (Assembled group) and 11 evacuees were surveyed through individual visits to their residences (Individual group). Evacuees in the Individual group agreed to participate in this study, but refused to visit the assembly hall to engage in exercise and recreation. Pain, quality of life (QOL) and level of activity were assessed with the Numeric Rating Scale (NRS), the MOS Short-Form 36 item Health Survey (SF-36) and a pedometer, respectively. Student's t-test, Mann-Whitney U test, and Fisher's exact test were used for statistical analysis. RESULTS: Forty-four (62.0 %) residents had chronic pain with a mean NRS of 2.74. Twenty-one (29.6 %) of these residents had relatively severe pain rated 5 or above on the NRS. QOL was significantly lower for the subscales of "physical functioning," "role physical", "general health", "social functioning", "role emotional" and "mental health", when compared with the national standard values. Values were also visibly lower for "physical component summary" in the summary score. On comparing the Assembled group and the Individual group, "physical function", "role physical", "social functioning" and "physical component summary" were found to be significantly lower in the Individual group. The mean daily number of steps was 1,892 in the Individual group and 4,579 in the Assembled group. The Individual group thus significantly took less mean daily number of steps compared with the Assembled group. CONCLUSIONS: This study quantified the state of pain, QOL and activity of aged evacuees living in temporary housing after the Great East Japan Earthquake. The evacuees frequently had chronic pain and lower physical and mental QOL scores compared to the national standard values. PMID- 26359244 TI - Elevated alpha1-acid glycoprotein in gastric cancer patients inhibits the anticancer effects of paclitaxel, effects restored by co-administration of erythromycin. AB - Paclitaxel (PTX) which easily elutes into ascites is widely used to treat gastric cancer patients with peritoneal carcinomatosis (PC), but clinical outcomes are suboptimal. Increased concentrations of alpha1-acid glycoprotein (AGP), an important drug-binding protein, have been reported in the plasma and ascites of cancer patients. This study sought to clarify whether AGP binds to PTX and alters its anticancer effects. AGP concentrations were measured in the serum and ascites of gastric cancer patients with PC and in the serum of healthy volunteers. The in vitro effects of AGP and AGP plus erythromycin (EM) on PTX were evaluated by MTT assays in the gastric cancer cell lines. We also measured AGP concentrations in the ascites of PC model mice and examined the effects of EM plus PTX on PC. The mean AGP concentrations in the serum and ascites of gastric cancer patients with PC were 1524 and 834 MUg/mL, respectively, higher than the mean AGP concentration of 650 MUg/mL observed in the sera of healthy volunteers. AGP > 400 MUg/mL significantly suppressed the cell growth inhibitory effect of PTX in vitro, but the co-administration of EM restored it. Elevated AGP concentrations were observed in the ascites of PC model mice. Administration of PTX alone did not markedly diminish PC, whereas co-administration of PTX and EM significantly reduced PC (p = 0.011). AGP is an important regulatory factor modulating the anticancer activity of intraperitoneal PTX. The co-administration of PTX and EM may be effective in treating gastric cancer patients with PC. PMID- 26359246 TI - The Retired Fly: Detecting Life History Transition in Individual Drosophila melanogaster Females. AB - Life history observations at the level of individual model organisms are relatively scarce, but highly informative. Here I analyze published data on the survival and lifetime fecundity of 3,971 individually housed, mated Drosophila melanogaster females from nine experimental populations. Data were collected from four laboratories and include counts of over 4.6 million eggs. Individual fecundity records are dominated by zero-egg-days (ZEDs). I show that the timing of ZEDs is informative about the survival and reproduction of individual flies. The first postmaturation ZED divides adult life into two functional stages: working and retired. The working stage is characterized by relatively high levels of oviposition and survival, while the retired stage is characterized by low levels of oviposition and reduced survival. The retired stage typically lasts one quarter of the total adult life span. The age of transition varies between flies; consequently age-synchronized cohorts will generally contain a mixture of working and retired flies, possibly influencing responses to experimental treatments. ZED can be used as a nonintrusive, real-time biomarker to distinguish live flies in the prime of life from those in a terminal state. PMID- 26359248 TI - Skin diseases in pediatric patients attending a tertiary dermatology hospital in Northern Tanzania: a cross-sectional study. AB - BACKGROUND: Skin diseases affect 21-87 % of children in developing countries in Africa. However, the spectrum of the skin diseases varies from region to region due to several factors such as genetics, socioeconomic and environmental. The aim of this study was to determine the spectrum of childhood skin diseases in Tanzania. METHODS: We conducted a prospective hospital- based cross-sectional study between September 2012 and August 2013 at a tertiary referral dermatology clinic. Children younger than 14 years presenting with new skin conditions were recruited. Diagnosis was mainly done clinically, but if the diagnosis was not clinically clear, further investigations were undertaken accordingly. RESULTS: A total of 340 patients were recruited of which 56 (16.5 %) had more than one skin condition. Both genders were equally affected. Infections and infestations accounted for the majority (43.5 %, n = 177) of the skin conditions followed by eczematous dermatitis (28.5 %, n = 116) and pigmentary disorders (7.4 %, n = 30). Among the 152 infectious skin diseases, fungal infections predominated (50.7 %, n = 77) in the infectious group followed by bacterial (29.6 %, n = 45), and viral (19.7 %, n = 30). CONCLUSIONS: Skin infections are still the main cause of dermatological consultations in children although with a reduced prevalence. Inflammatory skin conditions are increasing and can be attributed to improved socioeconomic status and HIV pandemic. PMID- 26359247 TI - Low Plasma Klotho Concentrations and Decline of Knee Strength in Older Adults. AB - BACKGROUND: Although the "anti-aging hormone" klotho is associated with sarcopenia in mice, the relationship between klotho and muscle strength in older adults is not well known. METHODS: Plasma klotho concentrations were measured in 2,734 older adults, aged 71-80 years, who participated in the Health, Aging and Body Composition Study, a prospective observational cohort study conducted in Memphis, TN and Pittsburgh, PA. Knee extension strength was measured using isokinetic dynamometry at baseline and follow-up 2 and 4 years later. Knee extension strength was normalized for weight. RESULTS: At baseline, participants in the highest tertile of plasma klotho had higher knee extension strength (beta = .72, standard error [SE] = .018, p < .0001) compared with those in the lowest tertile in a multivariable linear regression model adjusting for age, sex, race, smoking, study site, C-reactive protein, interleukin-6, and diabetes. Participants in the highest tertile of plasma klotho at baseline had less of a decline in knee strength over 4 years of follow-up (beta = -.025, SE = .011, p = .02) compared with those in the lowest tertile in a multivariable linear regression model adjusting for the same covariates above. CONCLUSIONS: Plasma klotho concentrations were an independent predictor of changes in knee strength over time in older adults. Further studies are needed to identify the biological mechanisms by which circulating klotho could modify skeletal muscle strength. PMID- 26359249 TI - Three Generations, Three Wars: African American Veterans. AB - PURPOSE: This article emerged from pilot research exploring experiences of war and suffering among African American veterans who served in World War II, Korean War, and Vietnam War. Men's experiences as soldiers reflected both racism and the social change that occurred in the Unites States while they served. DESIGN AND METHODS: We used techniques of narrative elicitation, conducting qualitative, ethnographic interviews with each of five veterans in his home. Interviews focused on unique and shared experiences as an African American man and a soldier. RESULTS: Three important themes emerged: (a) Expectations related to War -Although men viewed service to country as an expected part of life, they also expected equal treatment in war, which did not occur; (b) Suffering as an African American--Informants interpreted experiences of suffering in war as related to the lower status of African American servicemen; and (c) Perception of present identity--Each man was honed by the sum of his experiences, including those of combat, racism, and postwar opportunities and obstacles. IMPLICATIONS: From 40 to 70 years after the wars were fought, there are few scholarly narrative studies on African American veterans, despite the fact that Korean War Veterans are entering old-old age and few World War II Veterans are alive. The value of pilot research that offers narratives of unheard voices is significant; larger studies can interview more African American veterans to advance knowledge that might soon be lost. PMID- 26359250 TI - Understanding the low uptake of long-acting reversible contraception by young women in Australia: a qualitative study. AB - BACKGROUND: Australia has high rates of teenage pregnancy compared with many Western countries. Long-acting reversible contraception (LARC) offers an effective method to help decrease unintended pregnancies; however, current uptake remains low. The aim of this study was to investigate barriers to LARC use by young women in Australia. METHODS: Healthcare professionals were recruited through publicly available sources and snowball sampling to complete an interview about young women's access to and use of LARC. The sample consisted of general practitioners, nurses, medical directors of reproductive and sexual health organisations, a sexual health educator, and health advocates. In addition, four focus groups about LARC were conducted with young women (aged 17-25 years) recruited via health organisations and a university. The data were analysed thematically. RESULTS: Fifteen healthcare professionals were interviewed and four focus groups were conducted with 27 young women. Shared barriers identified included norms, misconceptions, bodily consequences, and LARC access issues. An additional barrier identified by young women was a perceived lack of control over hormones entering the body from LARC devices. Healthcare professionals also raised as a barrier limited confidence and support in LARC insertions. Strategies identified to increase contraceptive knowledge and access included increasing nurses' role in contraceptive provision and education, improving sex education in schools, and educating parents. CONCLUSIONS: Challenges remain for young women to be able to make informed choices about contraception and easily access services. More research is needed around innovative approaches to increase LARC knowledge and access, including examining the role of nurses in enhancing young women's reproductive health. PMID- 26359251 TI - The impact of previous ovarian surgery on ovarian reserve in patients with endometriosis. AB - BACKGROUND: To investigate the impact of previous ovarian surgery on ovarian reserve in patients with endometriosis. METHODS: A total of 829 female patients were recruited. Their medical records were reviewed retrospectively. Patients who had diagnoses of endometriosis or endometrioma were defined as the endometriosis group, and those without endometriosis were as the control group. We further divided these patients into four groups according to whether they had received ovarian surgeries before. Group 1: control group without previous surgery; Group 2: control group with previous surgery; Group 3: endometriosis group without previous surgery; Group 4: endometriosis group with previous surgery. The subgroups with endometrioma or not and different operative procedures were also analyzed. The parameters for comparison included age, body mass index, serum estradiol, follicle-stimulating hormone, luteinizing hormone, cancer antigen 125, and anti-Mullerian hormone (AMH) level. RESULTS: The level of serum AMH was highest in group 1 and lowest in group 4. The decline was significant between group 1 and group 4 (p < 0.05). The serum AMH level was lower in group 4 than in group 3 but no significant difference. Serum estradiol level was significantly higher in group 3 than in group 2 (p < 0.05). Cancer antigen 125 levels were both significantly higher in group 3 and group 4 as compared with group 1 and group 2 (p < 0.05). CONCLUSIONS: Performing repeated ovarian surgery in patients with recurrent endometriosis needs careful consideration and adequate patient counselling because of the predictable deteriorating ovarian reserve. PMID- 26359252 TI - Dynamic microvesicle release and clearance within the cardiovascular system: triggers and mechanisms. AB - Interest in cell-derived microvesicles (or microparticles) within cardiovascular diagnostics and therapeutics is rapidly growing. Microvesicles are often measured in the circulation at a single time point. However, it is becoming clear that microvesicle levels both increase and decrease rapidly in response to certain stimuli such as hypoxia, acute cardiac stress, shear stress, hypertriglyceridaemia and inflammation. Consequently, the levels of circulating microvesicles will reflect the balance between dynamic mechanisms for release and clearance. The present review describes the range of triggers currently known to lead to microvesicle release from different cellular origins into the circulation. Specifically, the published data are used to summarize the dynamic impact of these triggers on the degree and rate of microvesicle release. Secondly, a summary of the current understanding of microvesicle clearance via different cellular systems, including the endothelial cell and macrophage, is presented, based on reported studies of clearance in experimental models and clinical scenarios, such as transfusion or cardiac stress. Together, this information can be used to provide insights into potential underlying biological mechanisms that might explain the increases or decreases in circulating microvesicle levels that have been reported and help to design future clinical studies. PMID- 26359253 TI - Brown adipose tissue: a potential target in the fight against obesity and the metabolic syndrome. AB - BAT (brown adipose tissue) is the main site of thermogenesis in mammals. It is essential to ensure thermoregulation in newborns. It is also found in (some) adult humans. Its capacity to oxidize fatty acids and glucose without ATP production contributes to energy expenditure and glucose homoeostasis. Brown fat activation has thus emerged as an attractive therapeutic target for the treatment of obesity and the metabolic syndrome. In the present review, we integrate the recent advances on the metabolic role of BAT and its relation with other tissues as well as its potential contribution to fighting obesity and the metabolic syndrome. PMID- 26359254 TI - Development and characterization of cyclodextrin glucanotransferase as a maltoheptaose-producing enzyme using site-directed mutagenesis. AB - Cyclodextrin glucanotransferase (CGTase; EC 2.4.1.19) mainly produces cyclodextrins (CDs) using linear maltooligosaccharides. We performed site directed saturation mutagenesis on the +1 substrate-binding residue, H233, of CGTase from alkalophilic Bacillus sp. I-5 to prepare specific-length oligosaccharides. The obtained mutant CGTase, H233Y, primarily produced maltoheptaose (G7) using beta-CD via a hydrolysis reaction. A kinetic study of H233Y showed that the kcat/Km value of beta-CD was 7-fold greater than that of G7, which accounts for the accumulation of G7 during the H233Y enzyme reaction. A structure comparison of CGTases with H233Y modeling suggests that the substitution of H233Y may alter the position of the +1 subsite and slow the further hydrolysis of G7 after the ring-opening reaction. PMID- 26359255 TI - "I am alone and isolated": a qualitative study of experiences of women living with genital fistula in Uganda. AB - BACKGROUND: Globally, 2-3 million women are estimated to have a genital fistula, with an annual incidence of 50,000-100,000 women. Affected women remain silent within their communities, and their experiences often go unnoticed. Our objective was to explore the experiences of Ugandan women living with genital fistulas to understand how their lives were affected and how they coped with the condition. METHODS: We conducted 8 focus group discussions (FGDs) with 56 purposively selected women with a genital fistula seeking treatment at Mulago Hospital, Uganda. Data were transcribed and analysed using qualitative content analysis. RESULTS: Women with a fistula were living a physically changed and challenging life, living socially deprived and isolated, living psychologically stigmatised and depressed, and living marital and sexual lives that were no longer joyful. The women's experiences were full of life changes and coping strategies, and they used both problem- and emotion-focused coping strategies to deal with the challenges. They devised ways to reduce the smell of urine to reduce the stigma, rejection and isolation. While trying to cope, the women found themselves alone and isolated. Women either isolated themselves or were isolated by society, including by close relatives and their husbands. Their sex lives were no longer enjoyable, and generally, women felt a loss of their marital and sexual rights. CONCLUSION: Women with a fistula make adjustments in their lives to cope with the physical, social, psychological and sexual challenges. They use both problem- and emotion-focused coping to minimise their sense of isolation, as well as the rejection and stigma associated with fistula. These findings are essential for counselling patients, families and community members affected by a fistula. In similar contexts, health programmes should go beyond fistula closure and target communities and families to reduce the stigma and isolation faced by women with genital fistula. PMID- 26359257 TI - Breast Cancer Resistance Protein and P-Glycoprotein Influence In Vivo Disposition of 11C-Erlotinib. AB - (11)C-erlotinib is a PET tracer to distinguish responders from nonresponders to epidermal growth factor receptor-targeted tyrosine kinase inhibitors and may also be of interest to predict distribution of erlotinib to tissues targeted for treatment. The aim of this study was to investigate if the known interaction of erlotinib with the multidrug efflux transporters breast cancer resistance protein (humans, ABCG2; rodents, Abcg2) and P-glycoprotein (humans, ABCB1; rodents, Abcb1a/b) affects tissue distribution and excretion of (11)C-erlotinib and has an influence on the ability of (11)C-erlotinib PET to predict erlotinib tissue distribution at therapeutic doses. METHODS: Wild-type and Abcb1a/b or Abcg2 knockout mice underwent (11)C-erlotinib PET/MR scans, with or without the coinjection of a pharmacologic dose of erlotinib (10 mg/kg) or after pretreatment with the ABCB1/ABCG2 inhibitor elacridar (10 mg/kg). Integration plot analysis was used to determine organ uptake (CLuptake) and biliary excretion (CLbile) clearances of radioactivity. RESULTS: (11)C-erlotinib distribution to the brain was restricted by Abcb1a/b and Abcg2, and CLuptake into the brain was only significantly increased when both Abcb1a/b and Abcg2 were absent (wild-type mice, 0.017 +/- 0.004 mL/min/g of tissue; Abcb1a/b((-/-))Abcg2((-/-)) mice, 0.079 +/- 0.013 mL/min/g of tissue; P < 0.001). The pretreatment of wild-type mice with elacridar increased CLuptake into the brain to levels comparable to Abcb1a/b((-/ ))Abcg2((-/-)) mice (0.090 +/- 0.007 mL/min/g of tissue, P < 0.001). The absence of Abcb1a/b and Abcg2 led to a 2.6-fold decrease in CLbile (wild-type mice, 0.025 +/- 0.005 mL/min/g of tissue; Abcb1a/b((-/-))Abcg2((-/-)) mice, 0.0095 +/- 0.001 mL/min/g of tissue; P < 0.001). There were pronounced differences in distribution of (11)C-erlotinib to the brain, liver, kidney, and lung and hepatobiliary excretion into intestine between animals injected with a microdose and pharmacologic dose of erlotinib. CONCLUSION: ABCG2, ABCB1, and possibly other transporters influence in vivo disposition of (11)C-erlotinib and thereby affect its distribution to normal and potentially also tumor tissue. Saturable transport of erlotinib leads to nonlinear pharmacokinetics, possibly compromising the prediction of erlotinib tissue distribution at therapeutic doses from PET with a microdose of (11)C-erlotinib. The inhibition of ABCB1 and ABCG2 is a promising approach to enhance brain distribution of erlotinib to increase its efficacy in the treatment of brain tumors. PMID- 26359256 TI - A Phase II Study of 3'-Deoxy-3'-18F-Fluorothymidine PET in the Assessment of Early Response of Breast Cancer to Neoadjuvant Chemotherapy: Results from ACRIN 6688. AB - Our objective was to determine whether early change in standardized uptake values (SUVs) of 3'deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) using PET with CT could predict pathologic complete response (pCR) of primary breast cancer to neoadjuvant chemotherapy (NAC). The key secondary objective was to correlate SUV with the proliferation marker Ki-67 at baseline and after NAC. METHODS: This prospective, multicenter phase II study did not specify the therapeutic regimen, thus, NAC varied among centers. All evaluable patients underwent (18)F-FLT PET/CT at baseline (FLT1) and after 1 cycle of NAC (FLT2); 43 patients were imaged at FLT1, FLT2, and after NAC completion (FLT3). The percentage change in maximum SUV (%DeltaSUVmax) between FLT1 and FLT2 and FLT3 was calculated for the primary tumors. The predictive value of DeltaSUVmax for pCR was determined using receiver operating-characteristic curve analysis. The correlation between SUVmax and Ki-67 was also assessed. RESULTS: Fifty-one of 90 recruited patients (median age, 54 y; stage IIA-IIIC) met the eligibility criteria for the primary objective analysis, with an additional 22 patients totaling 73 patients for secondary analyses. A pCR in the primary breast cancer was achieved in 9 of 51 patients. NAC resulted in a significant reduction in %SUVmax (mean Delta, 39%; 95% confidence interval, 31 46). There was a marginal difference in %DeltaSUVmax_FLT1-FLT2 between pCR and no pCR patient groups (Wilcoxon 1-sided P = 0.050). The area under the curve for DeltaSUVmax in the prediction of pCR was 0.68 (90% confidence interval, 0.50 0.83; Delong 1-sided P = 0.05), with slightly better predictive value for percentage mean SUV (P = 0.02) and similar prediction for peak SUV (P = 0.04). There was a weak correlation with pretherapy SUVmax and Ki-67 (r = 0.29, P = 0.04), but the correlation between SUVmax and Ki-67 after completion of NAC was stronger (r = 0.68, P < 0.0001). CONCLUSION: (18)F-FLT PET imaging of breast cancer after 1 cycle of NAC weakly predicted pCR in the setting of variable NAC regimens. Posttherapy (18)F-FLT uptake correlated with Ki-67 on surgical specimens. These results suggest some efficacy of (18)F-FLT as an indicator of early therapeutic response of breast cancer to NAC and support future multicenter studies to test (18)F-FLT PET in a more uniformly treated patient population. PMID- 26359258 TI - Spatiotemporal PET Imaging of Dynamic Metabolic Changes After Therapeutic Approaches of Induced Pluripotent Stem Cells, Neuronal Stem Cells, and a Chinese Patent Medicine in Stroke. AB - This study aimed to use spatiotemporal PET imaging to investigate the dynamic metabolic changes after a combined therapeutic approach of induced pluripotent stem cells (iPSCs), neuronal stem cells (NSCs), and Chinese patent medicine in a rat model of cerebral ischemia-reperfusion injury. METHODS: Cerebral ischemia was established by the middle cerebral artery occlusion approach. Thirty-six male rats were randomly assigned to 1 of the 6 groups: control phosphate-buffered saline (PBS), Chinese patent medicine (Qing-kai-ling [QKL]), induced pluripotent stem cells (iPSCs), combination of iPSCs and QKL, neuronal stem cells (NSCs), and combination of NSCs and QKL. Serial (18)F-FDG small-animal PET imaging and neurofunctional tests were performed weekly. Autoradiographic imaging and immunohistochemical and immunofluorescent analyses were performed at 4 wk after stem cell transplantation. RESULTS: Compared with the PBS control group, significantly higher (18)F-FDG accumulations in the ipsilateral cerebral infarction were observed in 5 treatment groups from weeks 1-4. Interestingly, the most intensive (18)F-FDG accumulation was found in the NSCs + QKL group at week 1 but in the iPSCs + QKL group at week 4. The neurofunctional scores in the 5 treatment groups were significantly higher than that of the PBS group from week 3 to 4. In addition, there was a significant correlation between the PET imaging findings and neurofunctional recovery (P < 0.05) or glucose transporter-1 expression (P < 0.01). Immunohistochemical and immunofluorescence studies found that transplanted iPSCs survived and migrated to the ischemic region and expressed protein markers for cells of interest. CONCLUSION: Spatiotemporal PET imaging with (18)F-FDG demonstrated dynamic metabolic and functional recovery after iPSCs or NSCs combined with QKL in a rat model of cerebral ischemia reperfusion injury. iPSCs or NSCs combined with Chinese medicine QKL seemed to be a better therapeutic approach than these stem cells used individually. PMID- 26359259 TI - Presence of Postsystolic Shortening Increases the Likelihood of Coronary Artery Disease: A Rest Electrocardiography-Gated Myocardial Perfusion SPECT Study. AB - Postsystolic shortening (PSS), which is a delayed myocardial contraction that occurs after end-systole, has been considered an important diagnostic index of myocardial ischemia. Recent technological advancements in quantitative gated SPECT (QGS) software enables the left ventricular (LV) regional analysis and may be useful for PSS measurement. The purpose of this study was to evaluate whether PSS at the resting condition determined by QGS is useful to identify patients with coronary artery disease. METHODS: The study comprised 146 patients (mean age +/- SD, 71 +/- 8 y; 98 men) with normal LV wall motion (mean LV ejection fraction +/- SD, 72% +/- 9%) who underwent both coronary angiography and resting (99m)Tc tetrofosmin myocardial perfusion SPECT. The sum of the difference between post end-systolic maximal LV thickening and end-systolic LV thickening, designated PSS index, was calculated from 17 LV myocardial segments using QGS. RESULTS: The PSS index was significantly higher in patients with significant stenosis of the coronary artery than in the other patients (9.8 +/- 10.2 vs. 5.6 +/- 5.1; P < 0.01). A cutoff point of 6.0 of the PSS index had sensitivity, specificity, positive predictive value, and negative predictive values of 55%, 70%, 76%, and 47%, respectively, for the diagnosis of coronary artery disease. Multivariate logistic regression analysis demonstrated that a PSS index greater than 6.0 was an independent predictor for the presence of coronary artery disease (odds ratio, 2.46; 95% confidence interval, 1.1-5.4; P < 0.05). CONCLUSION: Among subjects with normal LV function, PSS index even in the resting condition determined using QGS may help to identify patients with coronary artery disease. PMID- 26359260 TI - The Cannabinoid Receptor-1 Is an Imaging Biomarker of Brown Adipose Tissue. AB - Recently, the existence of significant deposits of brown adipose tissue (BAT) in human adults was confirmed. Its role in the human metabolism is unknown but could be substantial. Inhibition of the cannabinoid receptor-1 (CB1) by the antagonist rimonabant (SR141716) has been associated with activation of BAT thermogenesis and weight loss in mice and rats. The role of peripheral and central CB1 in the activation of BAT merits further investigation. Here we developed a technique for quantifying CB1 in BAT by PET. METHODS: Sections of rat BAT and subcutaneous white adipose tissue (WAT) were stained for CB1 and uncoupling protein-1 by immunofluorescent staining. Binding of the radiolabeled CB1 antagonist (3R,5R)-5 (3-(18F-fluoromethoxy)phenyl)-3-(((R)-1-phenylethyl)amino)-1-(4-(trifluoromethyl) phenyl)pyrrolidin-2-one ((18)F-FMPEP-d2) to BAT in vivo and in vitro was assessed in rats by PET. RESULTS: We found that CB1 was colocalized with uncoupling protein-1 in BAT, but neither protein was found in WAT. Binding of the radiotracer to BAT sections (but not WAT) in vitro was high and displaceable by pretreatment with rimonabant. Deposits of BAT in rats had significant binding of (18)F-FMPEP-d2 in vivo, indicating high CB1 density. WAT deposits were negative for (18)F-FMPEP-d2, consistent with the immunofluorescent staining and in vitro results. CONCLUSION: (18)F-FMPEP-d2 PET can quantify CB1 density noninvasively in vivo in rats. CB1 is therefore a promising surrogate imaging biomarker for assessing the presence of BAT deposits as well as for elucidating the mechanism of CB1 antagonist-mediated weight loss. PMID- 26359262 TI - Performance of 11C-Pittsburgh Compound B PET Binding Potential Images in the Detection of Amyloid Deposits on Equivocal Static Images. AB - The goal of this study was to clarify whether binding potential (BP) images using (11)C-Pittsburgh compound B ((11)C-PiB) and dynamic PET can reliably detect cortical amyloid deposits for patients whose (11)C-PiB PET static images are ambiguous and whether visual ratings are affected by white matter retention. METHODS: Static and BP images were constructed for 85 consecutive patients with cognitive impairment after (11)C-PiB dynamic PET. Cortical uptake was visually assessed as positive, negative, or equivocal for both types of images. Quantitatively, the standardized uptake value ratio (SUVR) from the static image, the nondisplaceable BP from the dynamic image for mean gray matter uptake, and the ratio of gray matter uptake to white matter retention were compared among (11)C-PiB-positive, (11)C-PiB-equivocal, and (11)C-PiB-negative groups. RESULTS: Forty-three scans were visually assessed as (11)C-PiB-positive in both the static and the BP images. Ten scans were (11)C-PiB-equivocal in the static images. In 8 of them, the BP images were (11)C-PiB-positive, whereas the other 2 were (11)C PiB-equivocal. Thirty-two scans were assessed as (11)C-PiB-negative in the static images. In the BP images, 4 were (11)C-PiB-positive and 2 were (11)C-PiB equivocal. The mean gray matter uptake of (11)C-PiB in SUVR and nondisplaceable BP, respectively, showed statistically significant differences among the (11)C PiB-positive, (11)C-PiB-equivocal, and (11)C-PiB-negative groups. The ratio of gray matter uptake to white matter retention was lower in the BP images than static images from the (11)C-PiB-negative and (11)C-PiB-equivocal groups, whereas it was higher in the (11)C-PiB-positive group. CONCLUSION: (11)C-PiB PET BP images can clarify visual interpretation of clinical static (11)C-PiB-equivocal images by reducing the interference of nonspecific white matter retention. We conclude that (11)C-PiB-equivocal PET findings on static images reflect cortical amyloid deposits, which can be verified using BP images. Furthermore, quantitative assessments, such as SUVR and nondisplaceable BP, are of no use for correctly rating equivocal visual findings. PMID- 26359261 TI - 18F-FLT PET/CT in the Evaluation of Pheochromocytomas and Paragangliomas: A Pilot Study. AB - (18)F-FDG PET/CT has been proven to be a highly sensitive method for pheochromocytomas/paragangliomas (PHEOs/PGLs) associated with succinate dehydrogenase (SDH) mutations. This finding has been attributed to altered tumor cell metabolism resulting from these mutations and does not provide additional prognostic information to genotype. Therefore, identification of new biomarkers for aggressiveness is needed. A high Ki-67 index was proposed to be an additional prognostic factor. This pilot study aimed to evaluate 3'-deoxy-3'-(18)F fluorothymidine ((18)F-FLT) PET/CT, a PET proliferation tracer, as a potential imaging agent in a series of 12 PHEO/PGL patients with different genetic backgrounds, to compare (18)F-FLT uptake with (18)F-FDG PET/CT, and to evaluate classic factors of aggressiveness. METHODS: Twelve patients (7 metastatic and 5 nonmetastatic) were prospectively evaluated with (18)F-FDG and (18)F-FLT and followed for at least 2 y after the initial imaging work-up. Uptake was assessed at a lesion level, visually and quantitatively by maximum standardized uptake values (SUVmax) for both tracers. (18)F-FLT uptake was compared with risk factors known to be linked with a poor prognosis in PGLs (SDHB-mutated status, lesion size, dopaminergic phenotype) and with (18)F-FDG uptake. RESULTS: In 12 patients, 77 lesions were assessed. All lesions had low (18)F-FLT uptake (median SUVmax, 2.25; range, 0.7-4.5). There was no apparent superiority of (18)F-FLT uptake in progressive lesions, and most of the lesions showed a mismatch, with high (18)F FDG uptake (median SUVmax, 10.8; range, 1.1-79.0) contrasting with low (18)F-FLT uptake. CONCLUSION: This study suggests that PHEOs/PGLs-even those that progress do not exhibit intense (18)F-FLT uptake. It provides the first in vivo demonstration that proliferation may not be a major determinant of (18)F-FDG uptake in these tumors. These findings provide new insight into the biologic behavior of PGL and suggest that antiproliferative agents may be suboptimal for treatment of these tumors. PMID- 26359263 TI - Prognostic Value of Dual-Time-Point 18F-FDG PET for Idiopathic Pulmonary Fibrosis. AB - The aim of this prospective study was to clarify whether dual-time-point (18)F FDG PET imaging results are useful to predict long-term survival of idiopathic pulmonary fibrosis (IPF) patients. METHODS: Fifty IPF patients underwent (18)F FDG PET examinations at 2 time points: 60 min (early imaging) and 180 min (delayed imaging) after (18)F-FDG injection. The standardized uptake value (SUV) at each point and retention index value (RI-SUV) calculated from those were evaluated, and then the results were compared with overall and progression-free survival. RESULTS: A multivariate Cox proportional hazards model showed higher RI SUV and higher extent of fibrosis score as independent predictors of shorter progression-free survival. The median progression-free survival for patients with negative RI-SUV was better than that for those with positive RI-SUV (27.9 vs. 13.3 mo, P = 0.0002). On the other hand, multivariate Cox analysis showed higher RI-SUV and lower forced vital capacity to be independent predictors of shorter overall survival. The 5-y survival rate for patients with negative RI-SUV was better than that for those with positive RI-SUV (76.8% vs. 14.3%, P = 0.00001). In addition, a univariate Cox model showed that positive RI-SUV as a binary variable was a significant indicator of mortality (hazard ratio, 7.31; 95% confidence interval, 2.64-20.3; P = 0.0001). CONCLUSION: Our results demonstrate that positive RI-SUV is strongly predictive of earlier deterioration of pulmonary function and higher mortality in patients with IPF. PMID- 26359264 TI - Sodium persulfate-assisted mechanochemical degradation of tetrabromobisphenol A: Efficacy, products and pathway. AB - In recent years, activated persulfate (PS) oxidation has been developed as a new advanced oxidation process for the degradation of organic pollutants. On the other hand, the mechanochemical method has exhibited a unique advantage in dealing with chemical wastes. The degradation of tetrabromobisphenol A (TBBPA), a widely used brominated flame retardant (BFR), in wastes has attracted considerable attention. In this study, the efficacy of a CaO-mechanochemical (CaO MC) treatment system assisted by the addition of PS for the degradation of TBBPA was investigated. Under the optimum reaction conditions with a mole ratio of PS:CaO = 1:4 and less than 12.5% of TBBPA by mass, the degradation and debromination of TBBPA were completed within 2 h, while the mineralization was completed within 4 h. Characterization of the milled sample by XRD revealed that CaSO4 crystallization occurred. The TG results illustrate that there was little organic matter left after 4 h of milling. Raman and FT-IR spectra exhibited the TBBPA destruction process and disappearance of the organic groups. Through analysis by LC/MS/MS, seventeen intermediates were identified. The mechanism of TBBPA degradation by the PS-assisted CaO-MC treatment system was explained from two aspects, the course of crystallization and the degradation of TBBPA by activated PS, and two parallel initiation pathways were proposed. PMID- 26359266 TI - Corrigendum. PMID- 26359265 TI - The impact of the 'Better Care Better Value' prescribing policy on the utilisation of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers for treating hypertension in the UK primary care setting: longitudinal quasi-experimental design. AB - BACKGROUND: In April/2009, the UK National Health Service initiated four Better Care Better Value (BCBV) prescribing indicators, one of which encouraged the prescribing of cheaper angiotensin-converting enzyme inhibitors (ACEIs) instead of expensive angiotensin receptor blockers (ARBs), with 80 % ACEIs/20 % ARBs as a proposed, and achievable target. The policy was intended to save costs without affecting patient outcomes. However, little is known about the actual impact of the BCBV indicator on ACEIs/ARBs utilisation and cost-savings. Therefore, this study aimed to evaluate the impact of BCBV policy on ACEIs/ARBs utilisation and cost-savings, including exploration of regional variations of the policy's impact. METHODS: This cross-sectional study used data from the UK Clinical Practice Research Datalink. Segmented time-series analysis was applied to monthly ACEIs prescription proportion, adjusted number of ACEIs/ARBs prescriptions and costs. RESULTS: Overall, the proportion of ACEIs prescription decreased during the study period from 71.2% in April/2006 to 70.7% in March/2012, with a small but a statistically significant pre-policy reduction in its monthly trend of 0.02% (p < 0.001). Instantly after its initiation, the policy was associated with a sudden reduction in the proportion of ACEIs prescription; however, it resulted in a statistically significant increase in the post-policy monthly trend of ACEIs prescription proportion of 0.013% (p < 0.001), resulting in an overall post policy slope of -0.007%. Despite this post-policy induced increment, the policy failed to achieve the 80% target, which resulted in missing a potential cost saving opportunity. The pre-policy trend of the adjusted number of ACEIs/ARBs prescriptions was increasing; however, their trends declined after the policy implementation. The policy affected neither total ACEIs/ARBs cost nor individual ACEIs or ARBs costs. CONCLUSIONS: ACEIs/ARBs utilisation was not affected by the BCBV policy. The small increase in post-policy ACEIs prescription proportion was not associated with any savings. This study represents a case study of a failed or ineffective policy and thus provides key learning lessons for other healthcare authorities. Given the existing opportunity of potential cost-savings from achieving the 80 % target, specific measures would be needed to enhance the policy implementation and uptake; however, this must be balanced against other cost-saving policies in other high-priority areas. PMID- 26359267 TI - Orthostatic hypotension is associated with decreased cerebrospinal fluid levels of chromogranin A in early stage of Parkinson disease. AB - An association between the CSF chromogranin A (CgA) and orthostatic blood pressure changes was investigated in 20 patients in the early stage of Parkinson disease (PD). There was a positive correlation between the CSF CgA and diastolic blood pressure change, when CSF CgA levels were lower in patients with orthostatic hypotension (OH). Decreased CSF CgA may be useful in predicting OH in the early stage of PD. PMID- 26359268 TI - Residual sympathetic tone is associated with reduced insulin sensitivity in patients with autonomic failure. AB - PURPOSE: Parkinson disease, an alpha-synucleinopathy, is associated with reduced insulin sensitivity, impaired glucose tolerance, and diabetes mellitus. Importantly, these metabolic alterations have been shown to contribute to disease progression. The purpose of this study was to determine if reduced insulin sensitivity is also present in other alpha-synucleinopathies associated with autonomic failure. METHODS: We studied 19 patients with multiple system atrophy and 26 patients with pure autonomic failure. For comparison, we studied 8 healthy controls matched for body mass index. Insulin sensitivity and beta cell function were calculated using fasting glucose and insulin levels according to the homeostatic model assessment 2. A multiple linear regression model was performed to determine factors that predict insulin sensitivity in autonomic failure. RESULTS: There was a significant difference in insulin sensitivity among groups (P = 0.048). This difference was due to lower insulin sensitivity in multiple system atrophy patients: 64% [interquartile range (IQR), 43 to 117] compared to healthy controls 139% (IQR, 83 to 212), P = 0.032. The main factor that contributed to the reduced insulin sensitivity was the presence of supine hypertension and residual sympathetic tone. CONCLUSIONS: Multiple system atrophy patients have reduced insulin sensitivity that is associated with residual sympathetic activation and supine hypertension. These patients may therefore be at high risk for development of impaired glucose tolerance and diabetes mellitus. PMID- 26359269 TI - Evidence of increased cardiac parasympathetic drive in subjects meeting current physical activity recommendations. AB - INTRODUCTION: Aerobic fitness seems to provide extra protection to the cardiovascular system beyond changing the traditional risk factors, a phenomenon referred to as the risk factor gap model. Aerobic fitness may possibly lead to improved autonomic regulation. The Task Force of the American Heart Association supports a national campaign to reach specific cardiovascular health goals considering various metrics, including recommended physical activity (PA) volumes. It may be clinically relevant to assess whether autonomic remodeling occurs in those who adhere to the PA recommendations. METHODS: We studied 39 healthy subjects (22 males and 17 females), subdivided into two groups, according to whether they were meeting or not meeting PA recommendations (150 min/week of moderate aerobic activity, or 75 min/week of vigorous aerobic activity, or a combination of both). For each group, we evaluated aerobic capacity (VO2 Peak), body composition (Fat Mass) and autonomic nervous system profile, by way of mono and bivariate spectral analysis of cardiovascular beat by beat variability. RESULTS: Subjects following PA recommendations show higher RR period, higher RR variance, greater absolute power of the respiratory component of RR variability (HFRR) and higher index alpha (a measure of spontaneous baroreflex). Moreover, as expected, the group that was meeting or exceeding current PA recommendations had higher VO2 peak, less fat mass and greater weekly energy expenditure. CONCLUSION: Data show that subjects meeting current PA recommendations present a phenotype suggestive of enhanced parasympathetic drive to the SA node. This finding is compatible with the hypothesis that a more favorable autonomic profile is part of the mechanisms of the risk factor gap. PMID- 26359270 TI - In patient's with Parkinson disease, autonomic symptoms are frequent and associated with other non-motor symptoms. AB - BACKGROUND: Autonomic symptoms and sleep disorders are common non-motor symptoms of Parkinson disease (PD), which are correlated with poor quality of life for patients. PURPOSE: To assess the frequency of autonomic symptoms in a consecutive series of PD patients and to correlate them with other motor and non-motor symptoms. METHODS: All consecutive non-demented PD patients who underwent an extensive evaluation including Hoehn and Yahr staging, Unified Parkinson's Disease Rating Scale, Beck's Depression Inventory, Neuropsychiatric Inventory, PDQ-39 Scale, the Parkinson's diseases Sleep Scale, the Epworth Sleepiness Scale and SCOPA-AUT scale were enrolled. Comorbidity has been also considered. Supine to standing position blood pressure and cardiac frequency changes were also measured. RESULTS: 135 PD patients were included (mean age at interview 67.7; mean disease duration: 5.3 years). Patients were stratified according to mean SCOPA-AUT scale score (13.1). Those with higher SCOPA-AUT scale score were significantly older, had longer disease duration, worse disease stage, worse quality of sleep, were more severely affected, and were also taking a higher dosage of levodopa. At multivariate analysis, older age, longer disease duration, and worse quality of sleep were independently associated with higher SCOPA-AUT scale scores. CONCLUSIONS: Our results remark the role of autonomic symptoms in PD. In our patient population, characterized by mild to moderate disease severity, most of the patients complained of autonomic nervous system involvement (84%). A significant association between autonomic symptoms and sleep disorders was also observed. PMID- 26359271 TI - Predictors of 30-Day Readmission Following Inpatient Rehabilitation for Patients at High Risk for Hospital Readmission. AB - BACKGROUND: The proposed Centers for Medicare & Medicaid Services (CMS) 30-day readmission risk standardization models for inpatient rehabilitation facilities establish readmission risk for patients at admission based on a limited set of core variables. Considering functional recovery during the rehabilitation stay may help clinicians further stratify patient groups at high risk for hospital readmission. OBJECTIVE: The purpose of this study was to identify variables in the full administrative medical record, particularly in regard to physical function, that could help clinicians further discriminate between patients who are and are not likely to be readmitted to an acute care hospital within 30 days of rehabilitation discharge. DESIGN: This study used an observational cohort with a 30-day follow-up of Medicare patients who were deconditioned and had medically complex diagnoses and who were receiving postacute inpatient rehabilitation in 2010 to 2011. METHODS: Patients in the highest risk quartile for readmission (N=25,908) were selected based on the CMS risk prediction model. Hierarchical generalized linear models were built to compare the relative effectiveness of motor functional status ratings in predicting 30-day readmission. Classification and regression tree analysis was used to create a hierarchical order among predictors based on variable importance in classifying patients based on readmission status. RESULTS: Approximately 34% of patients in the high-risk quartile were readmitted within 30 days. Functional outcomes and rehabilitation length of stay were the best predictors of 30-day rehospitalization. A 3-variable algorithm classified 4 clinical subgroups with readmission probabilities ranging from 28% to 75%. LIMITATIONS: Although planned readmissions were accounted for in the outcome, potentially preventable readmissions were not distinguished from unpreventable readmissions. CONCLUSION: For older patients who are deconditioned and have medically complex diagnoses admitted to postacute inpatient rehabilitation, information on functional status measures that are easily monitored by health care providers may improve plans for care transition and reduce the risk of hospital readmission. PMID- 26359272 TI - Electronic health record-based triggers to detect adverse events after outpatient orthopaedic surgery. AB - BACKGROUND: Adverse events (AEs) after outpatient orthopaedic surgery are common, but difficult to detect. Electronic health records facilitate abstraction of large quantities of data, and may allow automated identification of 'triggers' or clues indicating the possibility of an AE. We evaluated electronic health record based triggers to detect AEs after outpatient orthopaedic surgery. METHODS: The medical records of 1464 patients undergoing outpatient surgical procedures in one of five orthopaedic services at our institution were manually reviewed for the occurrence of 90-day postoperative AEs. We used electronic health records to identify triggers suggestive of an AE. Each trigger was evaluated for positive predictive value (PPV). We constructed a logistic regression model to determine triggers associated with AEs and used the beta coefficients derived from the model to produce a formula for the likelihood of identifying an AE in the medical record. RESULTS: The overall rate of 90-day AEs was 10%, with surgical site infection being the most common (3.3%). Electronic triggers with the highest PPVs for the occurrence of 90-day AEs were antibiotic prescription (75%), emergency department visit (41%), bone/joint or blood culture (41%), repeat surgery (39%) and consult with infectious disease specialist (33%). Using our formula to predict the likelihood of identifying an AE in the medical record, a predicted probability of >0.10 had a specificity of 80% and sensitivity of 53% for actual AE. CONCLUSIONS: Electronic health record-based triggers may facilitate quality improvement efforts to monitor morbidity after outpatient orthopaedic surgery. Further research is needed to understand the optimal use of electronic triggers as surgical quality indicators and as screening tools to flag cases for manual review. LEVEL OF EVIDENCE: Level III, prognostic study. PMID- 26359273 TI - Are we ready for NICE? PMID- 26359274 TI - The CROWN Initiative: Journal editors invite researchers to develop core outcomes in women's health: The Core Outcomes in Women's Health (CROWN) Initiative. PMID- 26359275 TI - NICE sets out its stall on the menopause. PMID- 26359277 TI - Comment on "Fingolimod effects on left ventricular function in multiple sclerosis" Mult Scler 2015. PMID- 26359278 TI - Response to letter regarding article 'Fingolimod effects on left ventricular function in multiple sclerosis'. PMID- 26359279 TI - Progressive cerebral atrophy in neuromyelitis optica. AB - We report two cases of neuromyelitis optica patients with progressive cerebral atrophy. The patients exhibited characteristic clinical features, including elderly onset, secondary progressive tetraparesis and cognitive impairment, abnormally elevated CSF protein and myelin basic protein levels, and extremely highly elevated serum anti-AQP-4 antibody titer. Because neuromyelitis optica pathology cannot switch from an inflammatory phase to the degenerative phase until the terminal phase, neuromyelitis optica rarely appears as a secondary progressive clinical course caused by axonal degeneration. However, severe intrathecal inflammation and massive destruction of neuroglia could cause a secondary progressive clinical course associated with cerebral atrophy in neuromyelitis optica patients. PMID- 26359280 TI - Secondary progressive NMO, or concomitant NMO and a primary neurodegenerative disorder? PMID- 26359281 TI - Apgar-score in children prenatally exposed to antiepileptic drugs: a population based cohort study. AB - OBJECTIVES: It is unknown if prenatal exposure to antiepileptic drugs (AEDs) increases the risk of low Apgar score in offspring. SETTING: Population-based study using health registers in Denmark. PARTICIPANTS: We identified all 677 021 singletons born in Denmark from 1997 to 2008 and linked the Apgar score from the Medical Birth Register with information on the women's prescriptions for AEDs during pregnancy from the Danish Register of Medicinal Product Statistics. We used the Danish National Hospital Registry to identify mothers diagnosed with epilepsy before birth of the child. Results were adjusted for smoking and maternal age. RESULTS: Among 2906 children exposed to AEDs, 55 (1.9%) were born with an Apgar score <=7 as compared with 8797 (1.3%) children among 674 115 pregnancies unexposed to AEDs (adjusted relative risk (aRR)=1.41 (95% CI 1.07 to 1.85). When analyses were restricted to the 2215 children born of mothers with epilepsy, the aRR of having a low Apgar score associated with AED exposure was 1.34 (95% CI 0.90 to 2.01) When assessing individual AEDs, we found increased, unadjusted RR for exposure to carbamazepine (RR=1.86 (95% CI 1.01 to 3.42)), valproic acid (RR=1.85 (95% CI 1.04 to 3.30)) and topiramate (RR=2.97 (95% CI 1.26 to 7.01)) when compared to unexposed children. CONCLUSIONS: Prenatal exposure to AEDs was associated with increased risk of being born with a low Apgar score, but the absolute risk of a low Apgar score was <2%. Risk associated with individual AEDs indicate that the increased risk is not a class effect, but that there may be particularly high risks of a low Apgar score associated with certain AEDs. PMID- 26359282 TI - Geographic and socioeconomic variation of sodium and potassium intake in Italy: results from the MINISAL-GIRCSI programme. AB - OBJECTIVES: To assess geographic and socioeconomic gradients in sodium and potassium intake in Italy. SETTING: Cross-sectional survey in Italy. PARTICIPANTS: 3857 men and women, aged 39-79 years, randomly sampled in 20 regions (as part of a National cardiovascular survey of 8714 men and women). PRIMARY OUTCOME MEASURES: Participants' dietary sodium and potassium intakes were measured by 24 h urinary sodium and potassium excretions. 2 indicators measured socioeconomic status: education and occupation. Bayesian geoadditive models were used to assess spatial and socioeconomic patterns of sodium and potassium intakes accounting for sociodemographic, anthropometric and behavioural confounders. RESULTS: There was a significant north-south pattern of sodium excretion in Italy. Participants living in southern Italy (eg, Calabria, Basilicata and Puglia >180 mmol/24 h) had a significantly higher sodium excretion than elsewhere (eg, Val d'Aosta and Trentino-Alto Adige <140 mmol/24 h; p<0.001). There was a linear association between occupation and sodium excretion (p<0.001). When compared with occupation I (top managerial), occupations III and IV had a 6.5% higher sodium excretion (coefficients: 0.054 (90% credible levels 0.014, 0.093) and 0.064 (0.024, 0.104), respectively). A similar relationship was found between educational attainment and sodium excretion (p<0.0001). When compared with those with a university degree, participants with primary and junior school education had a 5.9% higher urinary sodium (coefficients: 0.074 (0.031, 0.116) and 0.038 (0.001, 0.075), respectively). The socioeconomic gradient explained the spatial variation. Potassium excretion was higher in central regions and in some southern regions. Those in occupation V (low-skill workers) showed a 3% lower potassium excretion compared with those in occupation I. However, the socioeconomic gradient only partially explained the spatial variation. CONCLUSIONS: Salt intake in Italy is significantly higher in less advantaged social groups. This gradient is independent of confounders and explains the geographical variation. PMID- 26359283 TI - Use and abuse of medication during 2014 FIFA World Cup Brazil: a retrospective survey. AB - OBJECTIVE: To examine the use of medication of top-level male players during the 2014 FIFA World Cup Brazil. DESIGN: Retrospective survey. PARTICIPANTS/INFORMATION: 736 top level players. SETTING: The teams' physicians disclosed a list of the medications used by each player within 72 h before each match of the 2014 FIFA World Cup Brazil. OUTCOME MEASURES: Average number of medications used per player per match or during the tournament; average number and percentage of players using at least one medication per match or during the tournament. RESULTS: 67.0% of all players took various types of medication during the tournament. The most used medications during the tournament were non steroidal anti-inflammatory drugs (NSAIDs), by 54.2% of all players, followed by analgaesics (12.6%); beta-2 agonists were only used by 0.5%. On average, 0.8 medications per player were used before each match. More players were reported taking medications during the knockout round than during the qualification round (0.36+/-0.48 vs 0.49+/-0.50, p<0.001). Players from the South American and Asian Confederations took twice as many medications per match as players from the African Confederation (1.17+/-1.55 and 1.01+/-1.26 vs 0.48+/-0.69, both p<0.001). CONCLUSIONS: There was high use of NSAIDs during the 2014 FIFA World Cup. Although the intake of NSAIDs per match (0.35+/-0.46 vs 0.31+/-0.48, p<0.01) in the 2014 FIFA World Cup decreased compared to the 2010 FIFA World Cup, the average use was still higher than in the 2006 FIFA World Cup, and the average number of all used medications per player remained the same level as 4 years prior, with all its implications for the player's health. More efforts need to be undertaken worldwide in order to reduce the administration of medications in sports, through continuous education for players, starting from a young age, as well as for doctors and paramedics. PMID- 26359284 TI - Association of 12 h shifts and nurses' job satisfaction, burnout and intention to leave: findings from a cross-sectional study of 12 European countries. AB - OBJECTIVES: 12 h shifts are becoming increasingly common for hospital nurses but there is concern that long shifts adversely affect nurses' well-being, job satisfaction and intention to leave their job. The aim of this study is to examine the association between working long shifts and burnout, job dissatisfaction, dissatisfaction with work schedule flexibility and intention to leave current job among hospital nurses. METHODS: Cross-sectional survey of 31,627 registered nurses in 2170 general medical/surgical units within 488 hospitals across 12 European countries. RESULTS: Nurses working shifts of >=12 h were more likely than nurses working shorter hours (<=8) to experience burnout, in terms of emotional exhaustion (adjusted OR (aOR)=1.26; 95% CI 1.09 to 1.46), depersonalisation (aOR=1.21; 95% CI 1.01 to 1.47) and low personal accomplishment (aOR=1.39; 95% CI 1.20 to 1.62). Nurses working shifts of >=12 h were more likely to experience job dissatisfaction (aOR=1.40; 95% CI 1.20 to 1.62), dissatisfaction with work schedule flexibility (aOR=1.15; 95% CI 1.00 to 1.35) and report intention to leave their job due to dissatisfaction (aOR=1.29; 95% CI 1.12 to 1.48). CONCLUSIONS: Longer working hours for hospital nurses are associated with adverse outcomes for nurses. Some of these adverse outcomes, such as high burnout, may pose safety risks for patients as well as nurses. PMID- 26359285 TI - Validation of a survey tool to assess the patient safety attitudes of pharmacy students. AB - OBJECTIVE: Patient safety education is a key strategy to minimise harm, and is increasingly being introduced into junior pharmacy curricula. However, currently there is no valid and reliable survey tool to measure the patient safety attitudes of pharmacy students. This study aimed to validate a modified survey tool, originally developed by Madigosky et al, to evaluate patient safety attitudes of junior pharmacy students. DESIGN: A 23-item cross-sectional patient safety survey tool was utilised to evaluate first and second year pharmacy students' attitudes during May 2013 with both exploratory and confirmatory factor analyses performed to understand the psychometric properties of the survey tool and to establish construct validity. SETTING: Undergraduate university students in Sydney, Australia PARTICIPANTS: 245 first year and 201 second year students enrolled in the Bachelor of Pharmacy Programme at The University of Sydney, Australia in May 2013. RESULTS: After exploratory factor analysis on first year student responses (55.76% variance explained) and confirmatory factor analysis on second year responses, a 5-factor model consisting of 14 items was obtained with satisfactory model fit (chi(2) (66)=112.83, p<0.001, RMSEA=0.06, CFI=0.91) and nesting between year groups (Deltachi(2)(7)=3.079, p=0.878). The five factors measured students' attitudes towards: (1) being quality improvement focused, (2) internalising errors regardless of harm, (3) value of contextual learning, (4) acceptability of questioning more senior healthcare professionals' behaviour and (5) attitude towards open disclosure. CONCLUSIONS: This study has established the reliability and validity of a modified survey tool to evaluate patient safety attitudes of pharmacy students, with the potential for use in course development and evaluation. PMID- 26359286 TI - Drug use and emotional distress differentiate unstably- versus stably-housed adults living with HIV who engage in unprotected sex. AB - Among adults living with HIV, unstable housing is a barrier to health. Stably- and unstably-housed adults living with HIV were assessed for over 25 months. At baseline, unstably-housed adults living with HIV had a more recent HIV diagnosis, higher viral loads, worse physical and mental health, lower rates of antiretroviral therapy use and insurance coverage, and higher rates of hard drug use than stably-housed adults living with HIV. At follow-up, the health of both groups was similar, but unstably-housed adults living with HIV reported significantly more hard drug use and mental health symptoms when compared to the stably-housed adults living with HIV. Drug and mental health risks decreased for both groups, but decreases in unprotected sex were greater among unstably-housed adults living with HIV. PMID- 26359288 TI - Narrative interventions for health screening behaviours: A systematic review. AB - Health information can be presented in different formats, such as a statistically based or a story-based (e.g. narrative) format; however, there is no consensus on the ideal way to present screening information. This systematic review summarizes the literature pertaining to narrative interventions' efficacy at changing screening behaviour and its determinants. Five psychology and public health databases were searched; 19 studies, 18 focused on cancer and 1 on sexual health, met eligibility criteria. There is consistent evidence supporting the efficacy of narratives, but mixed evidence supporting an advantage for narratives over statistical interventions for screening behaviour and its determinants. Further investigation is warranted. PMID- 26359287 TI - Health-related behaviours after 1 year of renal transplantation. AB - Health-related behaviours and psychological distress were examined after kidney transplantation. Patients were evaluated at 1 month, 6 months and 1 year after transplantation. Participants completed the Healthy Behaviours Questionnaire and the Hospital Anxiety and Depression Scale. No significant differences in Healthy Behaviours Questionnaire's total score and psychological comorbidity were observed at three time points. However, there was an increase in drug-consumer habits ( p < 0.05) and a reduction in sedentary lifestyle ( p < 0.05) at 6 months and 1 year. Moreover, at 1 year, post-transplant had increased the harmful health habits ( p < 0.05). In regression analysis, anxiety symptoms were significant predictors of Healthy Behaviours Questionnaire change at a year post transplantation. PMID- 26359289 TI - Relationships between pediatric obesity and maternal emotional states and attitudes. AB - OBJECTIVE: The goal of this study was to investigate depression and anxiety levels of mothers whose child (7-11 years) and adolescent (12-18 years) offspring had obesity, as well as those mothers' attitudes toward their children and their family relationships. METHOD: This is a cross-sectional, case-control study of 100 dyads. All mothers completed the Beck Depression Inventory, the State-Trait Anxiety Inventory, the Parental Attitude Research Instrument, and the Family Assessment Device. RESULTS: Maternal state anxiety in the group with obesity was significantly higher than controls (p = 0.03). As measured by Family Assessment Device, affective involvement (p = 0.05) and behavior control (p = 0.00) scores were significantly higher for those with obesity. Obesity and adolescence have independent effects on maternal state anxiety; affective involvement domain of family function is affected by both obesity and its interaction with adolescence, while behavior control domain is singularly affected by obesity. CONCLUSIONS: Our results may demonstrate that, for the mothers of children who have obesity, this condition may have an adverse effect on their lives and their family relationships. Pediatric obesity and developmental stage of offspring may have different effects on maternally reported psychometric variables. Cross-sectional design may hinder causal explanations. Further studies with longitudinal designs are needed. PMID- 26359290 TI - Multiple sclerosis associated genetic variants of CD226 impair regulatory T cell function. AB - Recent association studies have linked numerous genetic variants with an increased risk for multiple sclerosis, although their functional relevance remains largely unknown. Here we investigated phenotypical and functional consequences of a genetic variant in the CD226 gene that, among other autoimmune diseases, predisposes to multiple sclerosis. Phenotypically, effector and regulatory CD4(+) memory T cells of healthy individuals carrying the predisposing CD226 genetic variant showed, in comparison to carriers of the protective variant, reduced surface expression of CD226 and an impaired induction of CD226 after stimulation. This haplotype-dependent reduction in CD226 expression on memory T cells was abrogated in patients with multiple sclerosis, as CD226 expression was comparable to healthy risk haplotype carriers irrespective of genetic variant. Functionally, FOXP3-positive regulatory T cells from healthy carriers of the genetic protective variant showed superior suppressive capacity, which was again abrogated in multiple sclerosis patients. Mimicking the phenotype of human CD226 genetic risk variant carriers, regulatory T cells derived from Cd226-deficient mice showed similarly reduced inhibitory activity, eventually resulting in an exacerbated disease course of experimental autoimmune encephalomyelitis, the animal model of multiple sclerosis. Therefore, by combining human and mouse analyses we show that CD226 exhibits an important role in the activation of regulatory T cells, with its genetically imposed dysregulation impairing regulatory T cell function. PMID- 26359293 TI - Association between red blood cell distribution width and disease activity in patients with Behcet's disease. AB - OBJECTIVES: To examine associations between red blood cell distribution width (RDW) and organ involvement and disease activity in patients with Behcet's disease. METHODS: Haematological and inflammatory parameters including RDW, high sensitivity C-reactive protein (hsCRP) and erythrocyte sedimentation rate (ESR) were examined in patients with Behcet's disease and in healthy controls. Patients were divided into those with active or inactive disease. RESULTS: Data from 236 patients with Behcet's disease (77 with active and 159 with inactive disease) and 72 controls were analysed. RDW, ESR and hsCRP were significantly higher in patients with Behcet's disease than in controls, and in those with active disease compared with inactive disease or controls. In addition, ESR and hsCRP were significantly higher in those with inactive disease than controls. No correlations were found between hsCRP, ESR and RDW. No differences were observed in RDW, ESR or hsCRP between patients with or without ocular or vascular involvement. Multivariate logistic regression analysis revealed that RDW was significantly higher in active disease compared with inactive disease. CONCLUSIONS: RDW was increased in active disease compared with inactive disease. No relationships were found between organ involvement and RDW. RDW may be a cost effective, novel potential parameter to evaluate disease activity in Behcet's disease. PMID- 26359292 TI - Assessment of acute lung injury/acute respiratory distress syndrome using B-type brain natriuretic peptide. AB - OBJECTIVES: To investigate the clinical value of B-type natriuretic peptide (BNP) in the assessment of severity and prognosis in acute lung injury/acute respiratory distress syndrome (ALI/ARDS). METHODS: Plasma BNP level, arterial blood gases, serum C-reactive protein level, alveolar-arterial oxygen tension difference and oxygenation index were measured in patients with and without ALI/ARDS within 24 h of admission to an intensive care unit. Patients with ALI/ARDS were divided into mild, moderate or severe groups according to the degree of hypoxaemia. Survival >28 days was recorded. RESULTS: A total of 59 patients with ALI/ARDS and 14 patients without ALI/ARDS were included in the study. Of the patients with ALI/ARDS, 18 had mild hypoxaemia, 20 had moderate hypoxaemia and 21 had severe hypoxaemia. The mean +/- SD BNP level was significantly higher in all three ALI/ARDS groups (92.41 +/- 28.19 pg/ml, 170.64 +/- 57.34 pg/ml and 239.06 +/- 59.62 pg/ml, respectively, in the mild, moderate and severe groups) than in the non-ALI/ARDS group (47.27 +/- 19.63 pg/ml); the increase in BNP level with increasing severity was also statistically significant. When divided according to outcome, the BNP level in the death group (267.07 +/- 45.06 pg/ml) was significantly higher than in the survival group (128.99 +/- 45.42 pg/ml). CONCLUSIONS: The BNP level may be of value in evaluating severity and prognosis in patients with ALI/ARDS. PMID- 26359291 TI - Defining reliable disability outcomes in multiple sclerosis. AB - Prevention of irreversible disability is currently the most important goal of disease modifying therapy for multiple sclerosis. The disability outcomes used in most clinical trials rely on progression of Expanded Disability Status Scale score confirmed over 3 or 6 months. However, sensitivity and stability of this metric has not been extensively evaluated. Using the global MSBase cohort study, we evaluated 48 criteria of disability progression, testing three definitions of baseline disability, two definitions of progression magnitude, two definitions of long-term irreversibility and four definitions of event confirmation period. The study outcomes comprised the rates of detected progression events per 10 years and the proportions of the recorded events persistent at later time points. To evaluate the ratio of progression frequency and stability for each criterion, we calculated the proportion of events persistent over the five subsequent years once progression was achieved. Finally, we evaluated the clinical and demographic determinants characterising progression events and, for those that regressed back to baseline, determinants of their subsequent regression. The study population consisted of 16 636 patients with the minimum of three recorded disability scores, totalling 112 584 patient-years. The progression rates varied between 0.41 and 1.14 events per 10 years, with the length of required confirmation interval as the most important determinant of the observed variance. The concordance among all tested progression criteria was only 17.3%. Regression of disability occurred in 11-34% of the progression events over the five subsequent years. The most important determinant of progression stability was the length of the confirmation period. For the most accurate set of the progression criteria, the proportions of 3-, 6-, 12- or 24-month confirmed events persistent over 5 years reached 70%, 74%, 80% and 89%, respectively. Regression post progression was more common in younger patients, relapsing-remitting disease course, and after a smaller change in disability, and was inflated by higher visit frequency. These results suggest that the disability outcomes based on 3-6-month confirmed disability progression overestimate the accumulation of permanent disability by up to 30%. This could lead to spurious results in short-term clinical trials, and the issue may be magnified further in cohorts consisting predominantly of younger patients and patients with relapsing-remitting disease. Extension of the required confirmation period increases the persistence of progression events. PMID- 26359294 TI - The efficacy of intrauterine injection of human chorionic gonadotropin before embryo transfer in assisted reproductive cycles: Meta-analysis. AB - OBJECTIVES: A systematic review and meta-analysis to evaluate the effect of human chorionic gonadotropin (hCG) intrauterine injection before embryo transfer on the outcome of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). METHODS: Searches of PubMed(r), EMBASE(r), EBSCO, Web of Science(r), SCOPUS(r) and Cochrane Central Register of Controlled Trials were conducted to retrieve relevant randomized controlled trials (RCTs). Data were extracted and analysed. RESULTS: The meta-analysis included five RCTs (hCG group n = 680; control group n = 707). Intrauterine hCG injection significantly increased rates of biochemical, clinical and ongoing pregnancy compared with controls. There were no between-group differences in implantation or miscarriage rates. CONCLUSION: Women undergoing IVF/ICSI may benefit from intrauterine hCG injection before embryo transfer. PMID- 26359295 TI - Platelet-rich plasma gel composited with nondegradable porous polyurethane scaffolds as a potential auricular cartilage alternative. AB - Total auricular reconstruction is still a challenge, and autologous cartilage transplant is the main therapy so far. Tissue engineering provides a promising method for auricular cartilage reconstruction. However, although degradable framework demonstrated excellent initial cosmetic details, it is difficult to maintain the auricular contour over time and the metabolites tended to be harmful to human body. In this study, biocompatible and safe nondegradable elastic polyurethane was used to make porous scaffold in specific details by rapid prototyping technology. Platelet-rich plasma contains fibrin and abundant autologous growth factors, which was used as cell carriers for in vitro expanded cells. When crosslinking polyurethane framework, platelet-rich plasma and cells together, we successfully made polyurethane/platelet-rich plasma/cell composites, and implanted them into dorsal subcutaneous space of nude mice. The results showed that this method resulted in more even cell distribution and higher cell density, promoted chondrocyte proliferation, induced higher level expressions of aggrecan and type II collagen gene, increased content of newly developed glycosaminoglycans, and produced high-quality cartilaginous tissue. This kind of cartilage tissue engineering approach may be a potential promising alternative for external ear reconstruction. PMID- 26359296 TI - Uncoupling PIP2-calmodulin regulation of Kv7.2 channels by an assembly destabilizing epileptogenic mutation. AB - We show that the combination of an intracellular bi-partite calmodulin (CaM) binding site and a distant assembly region affect how an ion channel is regulated by a membrane lipid. Our data reveal that regulation by phosphatidylinositol(4,5)bisphosphate (PIP2) and stabilization of assembled Kv7.2 subunits by intracellular coiled-coil regions far from the membrane are coupled molecular processes. Live-cell fluorescence energy transfer measurements and direct binding studies indicate that remote coiled-coil formation creates conditions for different CaM interaction modes, each conferring different PIP2 dependency to Kv7.2 channels. Disruption of coiled-coil formation by epilepsy causing mutation decreases apparent CaM-binding affinity and interrupts CaM influence on PIP2 sensitivity. PMID- 26359297 TI - Focal-adhesion-independent integrin-alphav regulation of FAK and c-Myc is necessary for 3D skin formation and tumor invasion. AB - Integrins play crucial roles in epithelial adhesion, proliferation, wound healing and cancer. In the epidermis, the roles of many integrin subunits are incompletely defined and mechanistic details regarding their functions are lacking. We performed a multiplexed small hairpin (sh)RNA screen to define roles for each subunit in human organotypic skin. We show that integrin-alphav (also known as ITGAV) heterodimers are essential for epidermal generation, with integrin-alphav loss driving a keratinocyte G1-S cell cycle block. Surprisingly, integrin alphav is not localized within keratinocyte focal adhesions, and instead maintains proliferation by controlling cellular (c)-Myc translation through FAK, p38beta and p90RSK1. These phenotypes depend only on the binding partners of integrin-alphav--integrin beta5 and integrin beta6 (also known as ITGB5 and ITGB6, respectively). Through inducible depletion of integrin alphav in both normal organotypic epidermis and Ras-driven invasive neoplasia, we show that integrin alphav is required for de novo tissue generation and neoplastic invasion but that it is dispensable for epidermal maintenance. Heterodimers of integrin alphav with integrin beta5 (integrin alphavbeta5) or integrin beta6 (integrin alphavbeta6) are required to similar extents for neoplastic invasion, thus identifying integrin alphavbeta5 and integrin alphavbeta6 heterodimers as potential therapeutic targets for epidermal squamous cell carcinoma. PMID- 26359298 TI - Two-color fluorescent analysis of connexin 36 turnover: relationship to functional plasticity. AB - Gap junctions formed of connexin 36 (Cx36, also known as Gjd2) show tremendous functional plasticity on several time scales. Changes in connexin phosphorylation modify coupling in minutes through an order of magnitude, but recent studies also imply involvement of connexin turnover in regulating cell-cell communication. We utilized Cx36 with an internal HaloTag to study Cx36 turnover and trafficking in cultured cells. Irreversible, covalent pulse-chase labeling with fluorescent HaloTag ligands allowed clear discrimination of newly formed and pre-existing Cx36. Cx36 in junctional plaques turned over with a half-life of 3.1 h, and the turnover rate was unchanged by manipulations of protein kinase A (PKA) activity. In contrast, changes in PKA activity altered coupling within 20 min. New Cx36 in cargo vesicles was added directly to existing gap junctions and newly made Cx36 was not confined to points of addition, but diffused throughout existing gap junctions. Existing connexins also diffused into photobleached areas with a half time of less than 2 s. In conclusion, studies of Cx36-HaloTag revealed novel features of connexin trafficking and demonstrated that phosphorylation-based changes in coupling occur on a different time scale than turnover. PMID- 26359299 TI - Fission yeast kinesin-8 controls chromosome congression independently of oscillations. AB - In higher eukaryotes, efficient chromosome congression relies, among other players, on the activity of chromokinesins. Here, we provide a quantitative analysis of kinetochore oscillations and positioning in Schizosaccharomyces pombe, a model organism lacking chromokinesins. In wild-type cells, chromosomes align during prophase and, while oscillating, maintain this alignment throughout metaphase. Chromosome oscillations are dispensable both for kinetochore congression and stable kinetochore alignment during metaphase. In higher eukaryotes, kinesin-8 family members control chromosome congression by regulating their oscillations. By contrast, here, we demonstrate that fission yeast kinesin 8 controls chromosome congression by an alternative mechanism. We propose that kinesin-8 aligns chromosomes by controlling pulling forces in a length-dependent manner. A coarse-grained model of chromosome segregation implemented with a length-dependent process that controls the force at kinetochores is necessary and sufficient to mimic kinetochore alignment, and prevents the appearance of lagging chromosomes. Taken together, these data illustrate how the local action of a motor protein at kinetochores provides spatial cues within the spindle to align chromosomes and to prevent aneuploidy. PMID- 26359300 TI - EGF augments TGFbeta-induced epithelial-mesenchymal transition by promoting SHP2 binding to GAB1. AB - In many epithelial cells, epidermal growth factor (EGF) augments the epithelial mesenchymal transition (EMT) that occurs when cells are treated with transforming growth factor beta (TGFbeta). We demonstrate that this augmentation requires activation of SH2 domain-containing phosphatase-2 (SHP2; also known as PTPN11), a proto-oncogene. In lung and pancreatic cancer cell lines, reductions in E cadherin expression, increases in vimentin expression and increases in cell scatter rates were larger when cells were treated with TGFbeta and EGF versus TGFbeta or EGF alone. SHP2 knockdown promoted epithelial characteristics basally and antagonized EMT in response to TGFbeta alone or in combination with EGF. Whereas EGF promoted SHP2 binding to tyrosine phosphorylated GAB1, which promotes SHP2 activity, TGFbeta did not induce SHP2 association with phosphotyrosine containing proteins. Knockdown of endogenous SHP2 and reconstitution with an SHP2 mutant with impaired phosphotyrosine binding ability eliminated the EGF-mediated EMT augmentation that was otherwise restored with wild-type SHP2 reconstitution. These results demonstrate roles for basal and ligand-induced SHP2 activity in EMT and further motivate efforts to identify specific ways to inhibit SHP2, given the role of EMT in tumor dissemination and chemoresistance. PMID- 26359301 TI - Dexamethasone-induced cellular tension requires a SGK1-stimulated Sec5-GEF-H1 interaction. AB - Dexamethasone, a synthetic glucocorticoid, is often used to induce osteoblast commitment of mesenchymal stem cells (MSCs), and this process requires RhoA dependent cellular tension. The underlying mechanism is unclear. In this study, we show that dexamethasone stimulates expression of fibronectin and integrin alpha5 (ITGA5), accompanied by an increase in the interaction of GEF-H1 (also known as ARHGEF2) with Sec5 (also known as EXOC2), a microtubule (MT)-regulated RhoA activator and a component of the exocyst, respectively. Disruption of this interaction abolishes dexamethasone-induced cellular tension and GEF-H1 targeting to focal adhesion sites at the cell periphery without affecting dexamethasone induced levels of ITGA5 and fibronectin, and the extracellular deposition of fibronectin at adhesion sites is specifically inhibited. We demonstrate that dexamethasone stimulates the expression of serum-glucocorticoid-induced protein kinase 1 (SGK1), which is necessary and sufficient for the induction of the Sec5 GEF-H1 interaction. Given the function of SGK1 in suppressing MT growth, our data suggest that the induction of SGK1 through treatment with dexamethasone alters MT dynamics to increase Sec5-GEF-H1 interactions, which promote GEF-H1 targeting to adhesion sites. This mechanism is essential for the formation of fibronectin fibrils and their attachment to integrins at adhesion sites in order to generate cellular tension. PMID- 26359302 TI - Galactosylsphingosine (psychosine)-induced demyelination is attenuated by sphingosine 1-phosphate signalling. AB - Globoid cell leukodystrophy (Krabbe disease) is a rare infantile neurodegenerative disorder. Krabbe disease is caused by deficiency in the lysosomal enzyme galactocerebrosidase (GALC) resulting in accumulation, in the micromolar range, of the toxic metabolite galactosylsphingosine (psychosine) in the brain. Here we find that psychosine induces human astrocyte cell death probably via an apoptotic process in a concentration- and time-dependent manner (EC50 ~ 15 MUM at 4 h). We show these effects of psychosine are attenuated by pre treatment with the sphingosine 1-phosphate receptor agonist pFTY720 (fingolimod) (IC50 ~ 100 nM). Psychosine (1 MUM, 10 MUM) also enhances LPS-induced (EC50 ~ 100 ng/ml) production of pro-inflammatory cytokines in mouse astrocytes, which is also attenuated by pFTY720 (1 MUM). Most notably, for the first time, we show that psychosine, at a concentration found in the brains of patients with Krabbe disease (EC50 ~ 100 nM), directly induces demyelination in mouse organotypic cerebellar slices in a manner that is independent of pro-inflammatory cytokine response and that pFTY720 (0.1 nM) significantly inhibits. These results support the idea that psychosine is a pathogenic agent in Krabbe disease and suggest that sphingosine 1-phosphate signalling could be a potential drug target for this disorder. PMID- 26359303 TI - Altered N-glycosylation modulates TgrB1- and TgrC1-mediated development but not allorecognition in Dictyostelium. AB - Cell surface adhesion receptors play diverse functions in multicellular development. In Dictyostelium, two immunoglobulin-like adhesion proteins, TgrB1 and TgrC1, are essential components with dual roles in morphogenesis and allorecognition during development. TgrB1 and TgrC1 form a heterophilic adhesion complex during cell contact and mediate intercellular communication. The underlying signaling pathways, however, have not been characterized. Here, we report on a mutation that suppresses the tgrB-tgrC1-defective developmental arrest. The mutated gene alg9 encodes a putative mannosyl transferase that participates in N-linked protein glycosylation. We show that alteration in N linked glycosylation, caused by an alg9 mutation with a plasmid insertion (alg9(ins)) or tunicamycin treatment, can partially suppress the developmental phenotypes caused by tgrC1 deletion or replacement with an incompatible allele. The alg9(ins) mutation also preferentially primed cells toward a stalk-cell fate. Despite its effect on development, we found that altered N-linked glycosylation had no discernable effect on TgrB1-TgrC1-mediated allorecognition. Our results show that N-linked protein glycosylation can modulate developmental processes without disturbing cell-cell recognition, suggesting that tgrB1 and tgrC1 have distinct effects in the two processes. PMID- 26359304 TI - Cx30 exhibits unique characteristics including a long half-life when assembled into gap junctions. AB - In the present study we investigated the life cycle, trafficking, assembly and cell surface dynamics of a poorly characterized connexin family member, connexin 30 (Cx30; also known as GJB6), which plays a critical role in skin health and hearing. Unexpectedly, Cx30 localization at the cell surface and gap junctional intercellular communication was not affected by prolonged treatments with the endoplasmic reticulum (ER)-Golgi transport inhibitor brefeldin A or the protein synthesis inhibitor cycloheximide, whereas Cx43 (also known as GJA1) was rapidly cleared. Fluorescent recovery after photobleaching revealed that Cx30 plaques were rebuilt from the outer edges in keeping with older channels residing in the inner core of the plaque. Expression of a dominant-negative form of Sar1 GTPase led to the accumulation of Cx30 within the ER, in contrast to a report that Cx30 traffics via a Golgi-independent pathway. Co-expression of Cx30 with Cx43 revealed that these connexins segregate into distinct domains within common gap junction plaques, suggesting that their assembly is governed by different mechanisms. In summary, Cx30 was found to be an unusually stable, long-lived connexin (half-life >12 h), which may underlie its specific role in the epidermis and cochlea. PMID- 26359305 TI - Metabolic syndrome among diabetics and pre-diabetics of Jenu Kuruba tribe in Mysore district (JKDHS-2)--An evidence of metabolic abnormalities leading to increase in CVD's among Jenu Kuruba tribal population. AB - BACKGROUND: Metabolic syndrome is a cluster of clinical and metabolic abnormalities. In diabetics, other components of metabolic syndrome are an added risk factor for cardiovascular disease and all these cause mortality. Epidemiological transition is happening all over the world and tribes are not spared either. Identifying the extent of metabolic syndrome and its components in diabetics is vital for the prevention of cardiovascular diseases and other morbidities. OBJECTIVE: To estimate the prevalence of Metabolic Syndrome among diabetics and pre-diabetics of Jenu Kuruba tribe and compare the mean values of various components of metabolic syndrome among diabetics and pre-diabetics. METHODS: A community based cross sectional study was carried out among 7500 Jenu Kuruba tribal population in two phases. In phase I, total of 7500 subjects were screened for diabetes and hypertension and in phase II, a total of 249 diabetics and 310 pre-diabetics were identified and evaluated for metabolic syndrome. RESULTS: Prevalence of metabolic syndrome was estimated using NCEP ATP-III criteria. Metabolic syndrome was found in 84 (33.7%) of diabetics and 113 (36.4%) of pre-diabetic study subjects. Metabolic syndrome was highest in the 41-50 year age group. Lipid parameters such as total cholesterol, triglycerides and VLDL were significantly higher and HDL levels were significantly lower among subjects with metabolic syndrome as compared to subjects without metabolic syndrome. CONCLUSIONS: One third of diabetics and pre-diabetics had definable metabolic syndrome. Dyslipidemia is a significant component of metabolic syndrome. Epidemiological transitions are happening among Jenu Kuruba tribes and non communicable diseases are on the raise among them. PMID- 26359306 TI - Obesity perceptions and documentation among primary care clinicians at a rural academic health center. AB - BACKGROUND: Obesity recognition in primary care is important to address the epidemic. We aimed to evaluate primary care clinician-reported documentation, management practices, beliefs and attitudes toward obesity compared to body mass index (BMI) calculation, obesity prevalence and actual documentation of obesity as an active problem in electronic health record in a rural academic center. METHODS: Our target population for previously validated clinician survey was 56 primary care providers working at 3 sites. We used calendar year 2012 data for assessment of baseline system performance for metrics of documentation of BMI in primary care visits, and proportion of visits in patients with obesity with obesity as a problem. Standard statistical methods assessed the data. RESULTS: Survey response rate was 91%. Average age of respondents was 48.9 years and 62.7% were females. 72.5% clinicians reported having normal BMI. The majority of clinicians reported regularly documenting obesity as an active problem, and utilized motivational interviewing and basic good nutrition and healthy exercise. Clinicians identified lack of discipline and exercise time, access to unhealthy food and psychosocial issues as major barriers. Most denied disliking weight loss discussion or patients taking up too much time. In 21,945 clinic visits and 11,208 annual preventive care visits in calendar year 2012, BMI was calculated in 93% visits but obesity documentation as an active problem only 27% of patients meeting BMI criteria for obesity. CONCLUSIONS: Despite high clinician-reported documentation of obesity as an active problem, actual obesity documentation rates remained low in a rural academic medical center. PMID- 26359307 TI - Construction of a short form of the healthy eating behaviour inventory for the Japanese population. AB - INTRODUCTION: The present study constructed a short form of the Healthy Eating Behavior Inventory suitable for use in the Japanese culture (HEBI-J) and confirmed the scale's preliminary reliability and validity. METHODS: In Study 1, Japanese adults (N=75) completed a free-response questionnaire about healthy eating behaviours. Thematic analysis was used to identify three factors-balance, pattern, and restriction-associated with healthy eating behaviours and 12 items related to these healthy eating behaviours. In Study 2, Japanese office workers (N=784) completed two questionnaires regarding 12 items of healthy eating behaviours and the dietary stages of change. RESULTS: Confirmatory factor analysis demonstrated that the three-factor model was appropriate (GFI=.94, AGFI=.90, CFI=.90, RMSEA=.08, SRMR=.53). Reliability was confirmed by alpha coefficients and the Spearman-Brown formula. Concurrent validity was confirmed by the relationship between the healthy eating stages. CONCLUSIONS: This study demonstrated the preliminary reliability and validity of the HEBI-J. PMID- 26359308 TI - Future Research in Graves' Orbitopathy: From Priority Setting to Trial Design Through Patient and Public Involvement. PMID- 26359309 TI - Patients with Papillary Thyroid Carcinoma at Intermediate Risk of Recurrence According to American Thyroid Association Criteria Can Be Reclassified as Low Risk When the Postoperative Thyroglobulin Is Low. AB - BACKGROUND: According to American Thyroid Association (ATA), all patients with papillary thyroid carcinoma (PTC) should initially be classified regarding the risk of tumor recurrence. If a very high postoperative thyroglobulin (Tg) classifies patients as high risk of recurrence, it is reasonable to hypothesize that, at the other extreme, a low Tg may reclassify patients from intermediate to low risk. The objective of this study was to evaluate the rate of persistent/recurrent disease in intermediate-risk patients with low postoperative (before 131I) Tg, thereby evaluating whether these patients can be reclassified as low risk based on this finding already at the time of initial therapy rather than one to two years after radioiodine therapy. METHODS: A total of 181 patients with the following characteristics were evaluated: (i) diagnosis of PTC; (ii) submitted to total thyroidectomy with lymph node dissection in the case of a suspicion of metastases based on preoperative ultrasonography (US) or perioperative evaluation (cN1); (iii) apparently without persistent tumor after surgery; (iv) a postoperative stimulated Tg (sTg) <=2 ng/mL and negative anti-Tg antibodies (TgAb); and (v) considered to be at intermediate risk by ATA criteria. RESULTS: When evaluated 9-12 months after radioiodine therapy, 170 patients (94%) had a sTg <1 ng/mL and negative TgAb and a negative neck US (excellent response). Ten patients (5.5%) had a sTg >1 ng/mL (<=2 ng/mL) in the absence of apparent disease detected by imaging methods (indeterminate response). US detected cervical lymph node metastases (not detected at the time of 131I therapy) in one patient (incomplete structural response). During follow-up, recurrence was observed in 5/180 (2.7%) patients without apparent disease in the initial assessment. Thus, persistent or recurrent disease occurred in only 3.3% of cases. The 175 patients without tumor persistence/recurrence were not submitted to any additional therapy, and all had a Tg/thryoxine <1 ng/mL in the last assessment. There was no case of death related to the disease. CONCLUSIONS: This study suggests that intermediate-risk patients (according to ATA criteria) with a postoperative sTg <=2 ng/mL can be reclassified as low risk already at the time of initial therapy. PMID- 26359310 TI - Antithyroid Drug Use in Pregnancy and Birth Defects: Why Some Studies Find Clear Associations, and Some Studies Report None. AB - BACKGROUND: Rare cases of birth defects after the use of methimazole (MMI) or carbimazole to treat hyperthyroidism in early pregnancy have been reported since 1972, whereas propylthiouracil (PTU) has not been considered teratogenic. Recently, two studies reported birth defects after the use of MMI in early pregnancy to affect 2-4% of exposed children, and one study also found birth defects after the use of PTU. On the other hand, some published studies did not find associations between the use of thionamides and birth defects. SUMMARY: The methods used in the two positive and the four negative reports are reviewed. The two positive studies included a sufficient number of children exposed to MMI (n = 1231 and 1097) to evaluate the studied outcomes, whereas the four negative studies included a much lower number of exposed children (n = 73, 108, 30, and 124). Considering PTU, the birth defects observed in one study were in general milder and tended to be diagnosed and registered only when they resulted in complications and led to surgery after one year of age. None of the negative studies has investigated outcomes after one year of age. CONCLUSION: Studies finding no associations between early pregnancy exposure to antithyroid drugs and birth defects were either not sufficiently powered or did not study outcomes at optimal ages. PMID- 26359311 TI - Targeting Health Behaviors to Reduce Health Care Costs in Pediatric Psychology: Descriptive Review and Recommendations. AB - OBJECTIVE: Recent efforts to enhance the quality of health care in the United States while reducing costs have resulted in an increased emphasis on cost containment and the introduction of new payment plans. The purpose of this review is to summarize the impact of pediatric health behavior change interventions on health care costs. METHODS: A review of PubMed, PsycINFO, and PEDE databases identified 15 articles describing the economic outcomes of pediatric health behavior change interventions. Data describing the intervention, health outcome, and economic outcome were extracted. RESULTS: All interventions targeting cigarette smoking (n = 3) or the prevention of a chronic medical condition (n = 5) were predicted to avert hundreds of dollars in health care costs per patient. Five of the seven interventions targeting self-management were associated with reductions in health care costs. CONCLUSIONS: Pediatric health behavior change interventions may be a valuable component of efforts to improve population health while reducing health care costs. PMID- 26359312 TI - A mechanistic pharmacokinetic/pharmacodynamic model of factor D inhibition in cynomolgus monkeys by lampalizumab for the treatment of geographic atrophy. AB - Lampalizumab is an antigen-binding fragment of a humanized monoclonal antibody against complement factor D (CFD), a rate-limiting enzyme in the activation and amplification of the alternative complement pathway (ACP), which is in phase III clinical trials for the treatment of geographic atrophy. Understanding of the pharmacokinetics, pharmacodynamics, and biodistribution of lampalizumab following intravitreal administration in the ocular compartments and systemic circulation is limited but crucial for selecting doses that provide optimal efficacy and safety. Here, we sought to construct a semimechanistic and integrated ocular systemic pharmacokinetic-pharmacodynamic model of lampalizumab in the cynomolgus monkey to provide a quantitative understanding of the ocular and systemic disposition of lampalizumab and CFD inhibition. The model takes into account target-mediated drug disposition, target turnover, and drug distribution across ocular tissues and systemic circulation. Following intravitreal administration, lampalizumab achieves rapid equilibration across ocular tissues. Lampalizumab ocular elimination is relatively slow, with a tau1/2 of approximately 3 days, whereas systemic elimination is rapid, with a tau1/2 of 0.8 hours. Target independent linear clearance is predominant in the eye, whereas target-mediated clearance is predominant in the systemic circulation. Systemic CFD synthesis was estimated to be high (7.8 mg/day); however, the amount of CFD entering the eye due to influx from the systemic circulation was small (<10%) compared with the lampalizumab dose and is thus expected to have an insignificant impact on the clinical dose-regimen decision. Our findings support the clinical use of intravitreal lampalizumab to achieve significant ocular ACP inhibition while maintaining low systemic exposure and minimal systemic ACP inhibition. PMID- 26359314 TI - To what extent do community members' personal health beliefs and experiences impact what they consider to be important for their community-at-large? AB - BACKGROUND: Health assessments are used to prioritize community-level health concerns, but the role of individuals' health concerns and experiences is unknown. We sought to understand to what extent community health assessments reflect health concerns of the community-at-large versus a representation of the participants sampled. METHODS: We conducted a health assessment survey in 30 rural African American churches (n = 412). Multivariable logistic regression produced odds ratios examining associations between personal health concern (this health concern is important to me), personal health experience (I have been diagnosed with this health issue) and community health priorities (this health concern is important to the community) for 20 health issues. RESULTS: Respondents reported significant associations for 19/20 health conditions between personal health concern and the ranking of that concern as a community priority (all P < 0.05). Inconsistent associations were seen between personal health experience of a specific health condition and the ranking of that condition as a community priority. CONCLUSIONS: Personal health concerns reported by individuals in a study sample may impact prioritization of community health initiatives. Further research should examine how personal health concerns are formed. PMID- 26359313 TI - Effects of nicotinic acetylcholine receptor agonists in assays of acute pain stimulated and pain-depressed behaviors in rats. AB - Agonists at nicotinic acetylcholine receptors (nAChRs) constitute one drug class being evaluated as candidate analgesics. Previous preclinical studies have implicated alpha4beta2 and alpha7 nAChRs as potential mediators of the antinociceptive effects of (-)-nicotine hydrogen tartrate (nicotine) and other nAChR agonists; however, these studies have relied exclusively on measures of pain-stimulated behavior, which can be defined as behaviors that increase in frequency, rate, or intensity after presentation of a noxious stimulus. Pain is also associated with depression of many behaviors, and drug effects can differ in assays of pain-stimulated versus pain-depressed behavior. Accordingly, this study compared the effects of nicotine, the selective alpha4/6beta2 agonist 5 (123I)iodo-3-[2(S)-2-azetidinylmethoxy]pyridine (5-I-A-85380), and the selective alpha7 agonist N-(3R)-1-azabicyclo(2.2.2)oct-3-yl-4-chlorobenzamide in assays of pain-stimulated and pain-depressed behavior in male Sprague-Dawley rats. Intraperitoneal injection of dilute lactic acid served as an acute noxious stimulus to either stimulate a stretching response or depress the operant responding, which is maintained by electrical brain stimulation in an intracranial self-stimulation (ICSS) procedure. Nicotine produced a dose dependent, time-dependent, and mecamylamine-reversible blockade of both acid stimulated stretching and acid-induced depression of ICSS. 5-I-A-85380 also blocked both acid-stimulated stretching and acid-induced depression of ICSS, whereas N-(3R)-1-azabicyclo(2.2.2)oct-3-yl-4-chlorobenzamide produced no effect in either procedure. Both nicotine and 5-I-A-85380 were >=10-fold more potent in blocking the acid-induced depression of ICSS than in blocking the acid-induced stimulation of stretching. These results suggest that stimulation of alpha4beta2 and/or alpha6beta2 nAChRs may be especially effective to alleviate the signs of pain-related behavioral depression in rats; however, nonselective behavioral effects may contribute to apparent antinociception. PMID- 26359315 TI - Promoting early presentation of breast cancer in women over 70 years old in general practice. AB - BACKGROUND: Delay in presentation contributes to poorer survival of older women with breast cancer. Research has shown the effectiveness of the promoting early presentation (PEP) intervention when delivered by radiographers in the NHS Breast Screening Programme. This paper investigates the effectiveness of the intervention when delivered by practice nurses in general practice. METHODS: The Breast Cancer Awareness Measure was used to compare participants' awareness of breast cancer before, 1 month after and 12 months after the delivery of the PEP intervention. Five hundred and fifty-six women aged over 70 years took part, 308 of whom returned all three surveys. RESULTS: The intervention was associated with increased awareness of non-lump breast symptoms and reported breast check frequency. There was a marked increase in breast cancer awareness which persisted for 12 months. Less than 5% of women were classified as 'breast cancer aware' before the intervention, rising to over 25% 1 month afterwards. This percentage dropped slightly after 1 year to just below 20%. CONCLUSION: Delivery of the PEP intervention in general practice was very effective at raising the awareness of breast cancer among older women. Primary care settings are well placed to enhance the reach of this kind of intervention to at-risk women. PMID- 26359316 TI - MOF nanoparticles coated by lipid bilayers and their uptake by cancer cells. AB - We report the synthesis of MOF@lipid nanoparticles as a versatile and powerful novel class of nanocarriers based on metal-organic frameworks (MOFs). We show that the MOF@lipid system can effectively store dye molecules inside the porous scaffold of the MOF while the lipid bilayer prevents their premature release. Efficient uptake of the MOF@lipid nanoparticles by cancer cells makes these nanocarriers promising for drug delivery and diagnostic purposes. PMID- 26359317 TI - Primary ammonium/tertiary amine-mediated controlled ring opening polymerisation of amino acid N-carboxyanhydrides. AB - Stable commercial primary ammonium chlorides were combined with tertiary amines to initiate the controlled ring opening polymerisation of amino acid N carboxyanhydrides to yield polypeptides with defined end group structure, predetermined molar mass and narrow molar mass distribution. PMID- 26359318 TI - The CD27-CD70 pathway and pathogenesis of autoimmune disease. AB - OBJECTIVE: To critically examine current evidence regarding the role of the CD27 CD70 pathway in the pathophysiology of autoimmune disease with a focus on understanding the contributions of this pathway as a potential new therapeutic target for systemic lupus erythematosus and rheumatoid arthritis. METHODS: A PubMed search for articles was conducted using the following key words: ("CD27" OR "CD70") AND ("autoimmune disease" OR "systemic lupus erythematosus" OR "rheumatoid arthritis"). The search was limited to publications in English and included human and animal studies. The reference lists of identified articles were searched for further relevant citations. Publications on the list that was developed by this approach were assessed and those with relevance to CD27-CD70 pathway mediated pathophysiology in autoimmune disease were chosen for the detailed review. RESULTS: Data from human diseases and animal models document a major role for the CD27-CD70 receptor-ligand pair in providing signals that regulate T and B lymphocyte activation. The membrane receptor CD27 and its soluble form (sCD27) transmit co-stimulatory signals and induce activation and proliferation of T and B lymphocytes. CD70-expressing CD4 T lymphocytes are increased in autoimmune disease including systemic lupus erythematosus and rheumatoid arthritis and have been shown to produce pro-inflammatory cytokines. At the same time, preclinical evidence suggests that the outcome of CD27-CD70 signals may vary qualitatively between cell subsets and differentiation stages, especially for B lymphocytes. Blockade of the CD27-CD70 pathway has been shown to ameliorate disease manifestations in animal models including murine collagen induced arthritis and experimental colitis. CONCLUSION: Current evidence from animal models and human diseases suggests that CD27-CD70 pathway contributes to the pathophysiology of autoimmunity. Although a number of basic questions still remain open, the available findings suggest that targeting the components of this pathway could provide useful and novel therapeutic interventions. PMID- 26359320 TI - Autoimmune hemolytic anemia and venous thromboembolism: A systematic review and meta-analysis. AB - OBJECTIVE: To investigate the risk of venous thromboembolism (VTE) among patients with autoimmune hemolytic anemia (AIHA). METHODS: We conducted a systematic review and meta-analysis of observational studies that reported odds ratio, relative risk, hazard ratio or standardized incidence ratio comparing the risk of VTE in patients with AIHA versus participants without AIHA. Pooled risk ratio and 95% confidence intervals were calculated using a random-effect, generic inverse variance method of DerSimonian and Laird. RESULTS: Out of 592 potentially relevant articles, four studies (three cohort studies and one cross-sectional study) met our inclusion criteria and were included in the data analysis. The pooled risk ratio of VTE in patients with AIHA was 2.63 (95% CI, 1.37-5.05). The statistical heterogeneity of this study was high with an I(2) of 97%. CONCLUSIONS: Our study demonstrated a significantly increased risk of VTE among patients with AIHA. PMID- 26359321 TI - Bioavailable IGF-1 and its relationship with endothelial damage in a bi-ethnic population: The SABPA study. AB - INTRODUCTION: Insulin-like growth factor-1 (IGF-1) has vasculoprotective effects and can directly oppose endothelial dysfunction in several ways. To improve our understanding on the potential contribution of reduced IGF-1 to the development of vascular endothelial damage, we investigated the link between bioavailable IGF 1 and von Willebrand factor (vWF) as a marker of endothelial damage. We performed this study in black South African school teachers, known to be prone to hypertension. MATERIALS AND METHODS: From the larger Sympathetic activity and Ambulatory Blood Pressure in Africans (SABPA) study we included 179 black and 207 white non-diabetic men and women (aged 44.5 +/- 9.96 years). We measured ambulatory blood pressure and determined IGF-1, insulin-like growth factor binding protein 3 (IGFBP-3) and vWF antigen from blood samples. We used the molar IGF-1/IGFBP-3 ratio as an estimate of bioavailable IGF-1. RESULTS: Black individuals presented higher blood pressure and vWFag and lower IGF-1 than the white group (all p < 0.001). In multivariate-adjusted analyses, vWFag was inversely associated with IGF-1 (R(2) = 0.18; beta = -0.17; p = 0.044) and IGF 1/IGFBP-3 (R(2) = 0.18; beta = -0.17; p = 0.030) in blacks, with no associations in whites. Since IGF-1 is attenuated and vWFag elevated in diabetes, we included patients with diabetes (n = 38) and the aforementioned associations found in blacks remained robust. CONCLUSION: The inverse association between bioavailable IGF-1 and vWF in black South Africans suggests that suppressed IGF-1 may result in endothelial damage independent of traditional risk factors. PMID- 26359319 TI - Systemic Vascular Transduction by Capsid Mutant Adeno-Associated Virus After Intravenous Injection. AB - The ability to effectively deliver genetic material to vascular endothelial cells remains one of the greatest unmet challenges facing the development of gene therapies to prevent diseases with underlying vascular etiology, such as diabetes, atherosclerosis, and age-related macular degeneration. Herein, we assess the effectiveness of an rAAV2-based capsid mutant vector (Y272F, Y444F, Y500F, Y730F, T491V; termed QuadYF+TV) with strong endothelial cell tropism at transducing the vasculature after systemic administration. Intravenous injection of QuadYF+TV resulted in widespread transduction throughout the vasculature of several major organ systems, as assessed by in vivo bioluminescence imaging and postmortem histology. Robust transduction of lung tissue was observed in QuadYF+TV-injected mice, indicating a role for intravenous gene delivery in the treatment of chronic diseases presenting with pulmonary complications, such as alpha1-antitrypsin deficiency. The QuadYF+TV vector cross-reacted strongly with AAV2 neutralizing antibodies, however, indicating that a targeted delivery strategy may be required to maximize clinical translatability. PMID- 26359322 TI - Influence of acute glycaemic level on measures of myocardial infarction in non diabetic pigs. AB - OBJECTIVE: Patients with diabetes are at increased risk of experiencing myocardial infarction. The influence of the prevailing plasma glucose level on infarction and mortality after acute ischaemia is however unknown. The aim was to study the effect of the acute plasma glucose level on the myocardial infarction size in a closed-chest pig model. DESIGN: 38 non-diabetic pigs were randomised to hypoglycaemic (1.8-2.2 mmol/l; n = 15), normoglycaemic (5-7 mmol/l; n = 12) or hyperglycaemic glucose clamping (22-23 mmol/l; n = 11). After 30 min within glucose target myocardial infarction was induced for 30 min followed by reperfusion for 120 min. Hereafter the heart was double-stained to delineate infarction from viable tissue within the area at risk. RESULTS: Mean infarction size was 201 +/- 35 mm(2) (mean +/- SEM) in the hypoglycaemic group, 154 +/- 40 mm(2) in the normoglycaemic group and 134 +/- 40 mm(2) in the hyperglycaemic group, with no differences in infarction size, infarct/area at risk ratio or troponin T levels between the groups. There was no difference in incidence of ventricular fibrillation or mortality between the groups. CONCLUSION: No statistically significant associations were observed between the acute glycaemic level and measures of myocardial infarction, rates of ventricular fibrillation and subsequent premature death in the setting of acute ischaemia and reperfusion. PMID- 26359323 TI - Anti-Mullerian hormone testing: Evaluation of a novel method allowing more automation. AB - The anti-Mullerian hormone (AMH), a 140 kDa homodimeric glycoprotein of the transforming growth factor beta (TGF-beta) superfamily, is a useful serum biomarker of ovarian reserve. As an indicator, it mainly allows for the evaluation of primary ovarian insufficiency, the diagnosis of polycystic ovary syndrome (PCOS) and the prediction of the outcome of in vitro fertilization. Despite its increasing clinical importance, the methods for measuring AMH concentrations still require various manual steps. In this regard, our data showed that a novel fully-automated AMH immunoassay has excellent analytical performances, as well as a significant relationship with a well-established AMH enzyme linked immunosorbent assay (ELISA). The within- and between-run coefficients of variation (CV) of the new Elecsys((r)) AMH immunoassay were <= 2.5%. The limit of detection of this automated assay was 0.01 ng/mL. While the correlation between the Elecsys((r)) AMH method and the Ansh((r)) Labs Ultrasensitive AMH/MIS ELISA was excellent (r = 0.97, p < 0.0001), a bias was nonetheless observed. An automated assay format for AMH can certainly be advantageous in reducing the analysis turnaround time and in consolidating assay. However, AMH assays are not standardized and interchangeable, as confirmed by our study, and a transition to routine therefore requires a careful evaluation and close communication with physicians. PMID- 26359324 TI - Endothelial endoplasmic reticulum and nitrative stress in endothelial dysfunction in the atherogenic rabbit model. AB - Oxidative stress causes endothelial dysfunction which ultimately leads to atherogenesis, yet anti-oxidant therapy has failed to reduce human clinical outcomes. We hypothesise that endoplasmic reticulum stress and oxidative stress are both present in the endothelial layer of aorta with atherosclerosis. Rabbits were fed for 4 weeks a diet supplemented with 1% methionine +0.5% cholesterol (MC). Control animals received a normal diet. The endothelial function of the abdominal aorta was examined using organ bath techniques. Semi-quantitative immunohistochemistry was used to determine endothelial nitrotyrosine (for nitrative/oxidative stress) and glucose regulated protein 78 (GRP 78) and CHOP to determine endoplasmic reticulum stress. Endothelium dependent relaxation in response to acetylcholine significantly decreased in MC. Stress markers were significantly elevated in endothelia in MC compared to control. The total endothelial area examined for GRP78 increased by 8.4+/-0.25% in MC vs control (p=0.026) and C/EBP homologous protein (CHOP) increased by 21.9+/-0.05% in MC vs control (p=0.014). Nitrotyrosine increased by 13.3+/-0.03% in MC vs control (p=0.012). CONCLUSIONS: Both endoplasmic reticulum stress and nitrative stress are present during endothelial dysfunction. Treatment directed at both stresses might be beneficial in the prevention of atherosclerosis. PMID- 26359325 TI - Influence of different approaches of aortic valve replacement on the incidence of post-operative delirium in intermediate risk patients - a matched pair analysis. AB - OBJECTIVES: Evaluation of the risk for post-operative delirium (POD) after surgical or transfemoral aortic valve replacement (AVR) as an additional decision parameter for the choice of treatment in patients with an EuroScore (ES) between 10% and 20%. BACKGROUND: POD is well known as a not infrequent side effect of cardiac surgery necessitating extracorporeal circulation. In Germany a tendency to treat patients with ES <20% with transfemoral AVR (TF) instead of surgical AVR (SAVR) was observed in 2013. The risk of POD may influence the decision of physician and patient as to which procedure would be appropriate in the individual case. Therefore we performed an analysis of the incidence of POD in patients with comparable risk treated either with surgical or transfemoral aortic valve replacement. METHODS: Patients with elective or urgent need for AVR and EuroScore between 10% and 20% were extracted from the database of all isolated AVR procedures in Germany of 2013. As a result 3407 cases, 771 SAVR patients and 2636 TF patients with EuroScore 10-20%, were extracted from the complete data base of the German quality insurance registry for heart surgery. Two homogeneous groups with regard to the risk predicted by ES were built by case-control matches and compared for available variables. In a second step two groups with identical risk/co-morbidity profile for 10 variables were identified and analyzed with respect to POD and in-hospital mortality. RESULTS: A total of 763 pairs with EuroScore of 13.5% each could be determined. Mean age was 75.6 years (SAVR, 51.6% male) and 78.8 years (TF, 56.5% male). Incidence of POD with need for therapy (POD-T) was 12.8% after SAVR and 3.8% after TF, resulting in numbers needed to harm of 8 and 26 respectively. In-hospital death rate of patients with POD-T was 5.1% after SAVR and 3.3% after TF, and nearly identical compared with patients without POD-T. POD-T had a negative influence on the regular discharge procedure. Further matching resulted in two groups of 470 patients each with identical co morbidities and an age difference of 1 year but POD-T rates of 14.5% (SAVR) and 4.9% (TF); in-hospital mortality was 6.2% (SAVR) and 2.3% (TF). LIMITATIONS: The dataset contains valid data only for the period of hospital stay until discharge. Therefore conclusions about the duration and reversibility of POD, which are important parameters of quality of life and resource consumption as well as midterm consequences, cannot be estimated. The documentation of the German Federal Council asks only for POD and POD-T, a predefined definition of POD is not given; this may have some influence on the data. We therefore confined the analysis to only POD-T. In addition only a limited number of co-morbidities are documented. CONCLUSION: In patients with intermediate risk according to EuroScore (10-20%) the risk of post-operative delirium and in-hospital mortality is significantly higher after surgical aortic valve replacement than after transfemoral procedure. This may be considered for patient guidance and the decision as to which procedure is able to achieve the best result including minimizing side effects. PMID- 26359326 TI - Is dibotermin alfa a cost-effective substitute for autologous iliac crest bone graft in single level lumbar interbody spine fusion? AB - OBJECTIVES: To evaluate the cost-effectiveness of dibotermin alfa compared with autologous iliac crest bone graft (ICBG) for patients undergoing single level lumbar interbody spinal fusion in a UK hospital setting. METHODS: An individual patient data (IPD) meta-analysis of six randomized controlled clinical trials and two single arm trials compared dibotermin alfa on an absorbable collagen implantation matrix (ACIM) (n = 456) and ICBG (n = 244) on resource use, re operation rates, and SF-6D (Short form 6-dimension) health utility (total N = 700). Failure-related second surgery, operating time, post-operative hospital stay, and quality-adjusted life years (QALYs) derived from the IPD meta-analysis were included as inputs in an economic evaluation undertaken to assess the cost effectiveness of dibotermin alfa/ACIM versus ICBG for patients undergoing single level lumbar interbody spinal fusion. A four year time horizon and the United Kingdom (UK) National Health Service (NHS) and Personal Social Services (PSS) perspective was adopted in the base case, with sensitivity analyses performed to gauge parameter uncertainty. RESULTS: In the base case analysis, patients treated using dibotermin alfa/ACIM (12 mg pack) accrued 0.055 incremental QALYs at an incremental cost of L 737, compared with patients treated with ICBG. This resulted in an incremental cost-effectiveness ratio (ICER) of L 13,523, indicating that at a willingness-to-pay threshold of L 20,000, dibotermin alfa/ACIM is a cost-effective intervention relative to ICBG from the NHS and PSS perspective. CONCLUSIONS: In a UK hospital setting, dibotermin alfa/ACIM is a cost-effective substitute for ICBG for patients who require lumbar interbody arthrodesis. PMID- 26359327 TI - Two placebo-controlled, randomized withdrawal studies to evaluate the fentanyl 1 day patch in opioid-naive patients with chronic pain. AB - OBJECTIVE: To evaluate the efficacy and safety of fentanyl 1 day patch in opioid naive patients with non-cancer chronic pain insufficiently relieved by non-opioid analgesics. RESEARCH DESIGN AND METHODS: Two phase III placebo-controlled, double blind, group-comparison, randomized withdrawal studies were conducted in patients with osteoarthritis and/or low back pain (N01 study) and post-herpetic neuralgia, complex regional pain syndrome, or chronic postoperative pain (N02) in Japan. Both studies consisted of period I (10-29 days of titration, fentanyl 12.5-50.0 ug/h) and period II (12 weeks double-blind). CLINICAL TRIAL REGISTRATION: N01, NCT01008618; N02, NCT01008553 MAIN OUTCOME MEASURES: The primary endpoint was the number of days until study discontinuation due to insufficient pain relief in period II, and secondary endpoints included pain scored on visual analog scale (VAS), subject's overall assessment, the number of rescue dose, brief pain inventory short form score, score on short-form 36-item health survey version 2.0, physician's overall assessment, and assessment of adverse events. RESULTS: Of the 218 (N01) and 258 (N02) subjects who entered period I, 150 and 163 subjects entered period II, respectively. In the N01 study, the between-group difference was significant in the VAS score (95% CI: 7.3 [1.1, 13.5] mm, P = 0.0215) but not in the primary endpoint (P = 0.0846, log-rank test). In the N02 study, both primary efficacy (P = 0.0003) and VAS (8.7 [2.4, 15.0] mm, P = 0.0071) results showed that fentanyl was more effective than placebo. The major adverse events were nervous system and gastrointestinal disorders typically associated with opioid analgesic use. The incidence of adverse events in the fentanyl group was 68.5% to 85.7%. CONCLUSIONS: Although the primary efficacy results showed significant effects of fentanyl in the N02 but not the N01 study, overall results showed that fentanyl 1 day patch is effective and well tolerated. PMID- 26359328 TI - Overall safety profile and effectiveness of tramadol hydrochloride/acetaminophen in patients with chronic noncancer pain in Japanese real-world practice. AB - OBJECTIVE: To evaluate the overall safety profile and clinical effectiveness of tramadol hydrochloride/acetaminophen (TA) combination tablets in Japanese patients with chronic noncancer pain unrelieved by non-opioid drugs for up to 12 weeks in real-world practice. RESEARCH DESIGN AND METHODS: This survey was a multicenter, prospective, longitudinal registry on the use of TA as a newly initiated pain treatment for chronic noncancer pain incurable by non-opioid analgesics that was conducted under the Good Post Marketing Study Practice regulation controlled by the Japan Ministry of Health, Labor and Welfare. Collected data included socio-demographics, treatment information, incidence of adverse drug reactions (ADRs), numerical rating scale for intensity of pain, EuroQol-5D (EQ-5D) scale, and physician's global impression (PGI) during the 12 week observation period. RESULTS: A total of 1316 patients were registered. ADRs were reported in 259 patients (20.5%); most events were nonserious (99.4%), including nausea (n = 87 [6.9%]), constipation (n = 63 [5.0%]), dizziness and somnolence (n = 29 [2.3%] each), and vomiting (n = 21 [1.7%]). No event related to drug dependence or respiratory depression was reported. In addition, 82.8% of patients showed acceptable effectiveness based on PGI at Week 4. Numerical rating scale for intensity of pain and EQ-5D utility scores were improved by -2.7 (SD 2.3) and 0.16 (SD 0.20) at Week 4, respectively, and the improvement was maintained until Week 12. CONCLUSION: This is a first report to evaluate the risk benefit profile of TA in Japanese real-world practice using large size registry data. It is suggested that the favorable risk-benefit balance of TA was confirmed for patients with chronic noncancer pain unrelieved by non-opioid drugs in real world practice. Limitations of this study were those inherent to open-label and non-interventional study designs. TRIAL REGISTRATION: This registry survey is registered at umin.ac.jp (identifier: UMIN000015901). PMID- 26359329 TI - Serum prealbumin is an independent predictor of mortality in systemic sclerosis outpatients. AB - OBJECTIVE: Serum prealbumin is a recognized marker of malnutrition, but its role in the prognosis of patients with SSc has not yet been investigated. The aim of the present multicentre prospective study was to investigate the association between prealbumin and mortality, independent of clinical features, in a cohort of SSc outpatients. METHODS: Patients were followed up according to standard clinical guidelines with visits at least every 6 months. Data collected included records of skin and internal organ involvement, survival and causes of death. RESULTS: During a median follow-up of 48 months [interquartile range (IQR) 25 58], 34/299 patients (11%) died. In univariable survival analysis, age; male sex; lung, gastrointestinal or multiple visceral organ involvement (two or more); co morbidities (two or more) and low serum prealbumin were significant predictors of mortality. In bivariable Cox models, alternatively adjusted for significant predictors, prealbumin was independently and significantly associated with the outcome. Mortality rates were particularly influenced by low prealbumin in patients without significant co-morbidities or multiple organ involvement. CONCLUSION: In SSc patients, low serum prealbumin is an independent predictor of mortality, particularly in those without significant internal organ involvement. Further research on this nutritional marker is warranted. PMID- 26359330 TI - Immunopathology of synovitis: from histology to molecular pathways. AB - Increased knowledge about pathological processes active in inflammatory joint diseases is needed to initiate personalized medicine based on targeted treatments in the future. The molecular and cellular pathways that are active during joint inflammation may differ between the various inflammatory joint diseases, between different patient subgroups within one disease, or even between different stages of the disease in a single patient. In this review, we evaluate synovial inflammation in terms of descriptive histopathology through to more functional studies on human synovial tissue inflammation in RA and SpA, in phenotypic subgroups of RA and SpA patients, and during the disease course of both diseases. PMID- 26359331 TI - Adherence to standard-dose or low-dose statin treatment and low-density lipoprotein cholesterol response in type 2 diabetes patients. AB - OBJECTIVE: To determine the association between adherence, dose and low-density lipoprotein (LDL) cholesterol response in patients with type 2 diabetes initiating statin treatment. RESEARCH DESIGN AND METHODS: This cohort study was performed using data for 2007-2012 from the Groningen Initiative to Analyse Type 2 Diabetes Treatment (GIANTT) database. The association between adherence to a standard-dose statin and LDL cholesterol response was assessed using linear regression, adjusting for covariates. The effect of low-dose versus standard-dose was assessed in a propensity-score matched cohort. Adherence rates, defined as the proportion of days covered (PDC), were estimated between statin initiation and LDL outcome measurement. MAIN OUTCOME MEASURE: LDL cholesterol level at follow-up. RESULTS: The effect of adherence on LDL cholesterol response, measured in 2160 patients, was dependent on the baseline LDL cholesterol level. For patients with a baseline LDL cholesterol of 3.7 mmol/l and an adherence rate of 80%, a 40% reduction in LDL cholesterol was predicted. In the matched sample of 1144 patients, the treatment dose showed a difference in impact on the outcome for adherence rates higher than 50%. It was estimated that a patient with a baseline LDL cholesterol of 3.7 mmol/l will need an adherence rate of at least 76% on low-dose and 63% on standard-dose treatment to reach the LDL cholesterol target of 2.5 mmol/l. LIMITATIONS: Adherence was measured as the PDC, which is known to overestimate actual adherence. Also, we were not able to adjust for lifestyle factors. CONCLUSIONS: We determined the concurrent effect of treatment adherence and dose on LDL cholesterol outcomes. Given the adherence levels seen in clinical practice, diabetes patients initiating statin treatment are at high risk of not reaching the recommended cholesterol target, especially when they start on a low-dose statin. PMID- 26359332 TI - Improving the management of post-operative acute pain: priorities for change. AB - Poor management of post-operative acute pain can contribute to medical complications including pneumonia, deep vein thrombosis, infection and delayed healing, as well as the development of chronic pain. It is therefore important that all patients undergoing surgery should receive adequate pain management. However, evidence suggests this is not currently the case; between 10% and 50% of patients develop chronic pain after various common operations, and one recent US study recorded >80% of patients experiencing post-operative pain. At the first meeting of the acute chapter of the Change Pain Advisory Board, key priorities for improving post-operative pain management were identified in four different areas. Firstly, patients should be more involved in decisions regarding their own treatment, particularly when fateful alternatives are being considered. For this to be meaningful, relevant information should be provided so they are well informed about the various options available. Good physician/patient communication is also essential. Secondly, better professional education and training of the various members of the multidisciplinary pain management team would enhance their skills and knowledge, and thereby improve patient care. Thirdly, there is scope for optimizing treatment. Examples include the use of synergistic analgesia to target pain at different points along pain pathways, more widespread adoption of patient-controlled analgesia, and the use of minimally invasive rather than open surgery. Fourthly, organizational change could provide similar benefits; introducing acute pain services and increasing their availability towards the 24 hours/day ideal, greater adherence to protocols, increased use of patient-reported outcomes, and greater receptivity to technological advances would all help to enhance performance and increase patient satisfaction. It must be acknowledged that implementing these recommendations would incur a considerable cost that purchasers of healthcare may be unwilling or unable to finance. Nevertheless, change is under way and the political will exists for it to continue. PMID- 26359333 TI - Healthcare utilization and costs associated with dabigatran compared to warfarin treatment in newly diagnosed patients with non-valvular atrial fibrillation. AB - PURPOSE: Real-world healthcare resource utilization and costs were compared among patients with non-valvular atrial fibrillation (NVAF) receiving either dabigatran or warfarin. METHODS: A retrospective cohort study was conducted using administrative claims data from the United States Department of Defense (DOD) Military Health System. Patients with newly diagnosed AF initiated on dabigatran or warfarin were identified using ICD-9 diagnosis, procedure and drug codes. Patients were observed for 3 months prior to treatment initiation to ascertain a diagnosis of valvular heart disease and 12 months for exclusion of those with a history of anticoagulation therapy. Propensity score matching was used to balance baseline characteristics between the two treatment cohorts. Medical and pharmacy utilization and costs were compared between the dabigatran and warfarin treatment groups for 3 and 12 months following treatment initiation. RESULTS: A total of 1102 patients with newly diagnosed NVAF initiated on dabigatran were matched with corresponding warfarin-treated patients. In the 12 months following initiation of anticoagulation, the mean medical costs for patients initiated on dabigatran were significantly lower than for patients initiated on warfarin (-$6299, p < 0.001), largely due to fewer hospitalizations (-0.162, p = 0.009). While pharmacy costs were higher ($4369, p < 0.001) for dabigatran, overall healthcare costs were significantly lower compared with patients on warfarin (12 months: -$1940, p < 0.001). Mean hospital length of stay between these two groups were similar (6.033 days for dabigatran vs 6.318 days for warfarin, p = 0.139). CONCLUSION: Despite higher pharmacy costs for NVAF patients initiated on dabigatran vs warfarin, this was more than offset by lower utilization of medical care resources. PMID- 26359334 TI - THE INFLUENCE OF PRE- AND POST-IRRADIATION ANNEALING ON LiF:Mg,Cu,P STABILITY. AB - The influence of pre- and post-irradiation annealing procedures on LiF:Mg,Cu,P (trade name MCP-N) thermoluminescent detector stability was investigated. The detectors were processed in four groups, undergoing complete or incomplete preparation cycles (containing pre- and/or post-irradiation annealing in various combinations). Each cycle was repeated 10 times. The decrease in the stability was observed in groups with pre-irradiation annealing procedure, and not observed in other groups that were found to be apparently stable. The influence of the thermal history on the properties of the detectors was also investigated by swapping the chosen groups of detectors with respect to the annealing cycles. Changes in the properties of the detectors were observed after next 10 cycles of measurements too. Exponential model was proposed to describe the trends observed at two parts of the experiment. Its application for the dose corrections related to the cycle number of the readout improves the accuracy of final dose determination. PMID- 26359335 TI - MICRODOSIMETRIC MEASUREMENTS OF A TISSUE-EQUIVALENT PROPORTIONAL COUNTER BASED ON A GAS ELECTRON MULTIPLIER DOWN TO 140 nm SIMULATED SITE SIZES. AB - A multi-element tissue-equivalent proportional counter (TEPC), based on a gas electron multiplier, has been constructed with several cavities of small dimensions (down to 0.5 mm of diameter), to be used for microdosimetric measurements in intense, pulsed, radiation fields. First micro- and nano dosimetric spectra with low-energy X rays in various simulated tissue site sizes are presented. The specific advantages and the calibration methods of this type of TEPC are discussed. PMID- 26359336 TI - Direct observation of ultrafast collective motions in CO myoglobin upon ligand dissociation. AB - The hemoprotein myoglobin is a model system for the study of protein dynamics. We used time-resolved serial femtosecond crystallography at an x-ray free-electron laser to resolve the ultrafast structural changes in the carbonmonoxy myoglobin complex upon photolysis of the Fe-CO bond. Structural changes appear throughout the protein within 500 femtoseconds, with the C, F, and H helices moving away from the heme cofactor and the E and A helices moving toward it. These collective movements are predicted by hybrid quantum mechanics/molecular mechanics simulations. Together with the observed oscillations of residues contacting the heme, our calculations support the prediction that an immediate collective response of the protein occurs upon ligand dissociation, as a result of heme vibrational modes coupling to global modes of the protein. PMID- 26359338 TI - Suspected vitreous seeding of uveal melanoma: relevance of diagnostic vitrectomy. AB - AIM: To review all cases of suspected vitreous seeding of treated or untreated uveal melanoma at our clinic and to compare clinical, cytological and histological findings with patients' survival. METHODS: Retrospective non randomised study of 23 patients with consecutive uveal melanoma who underwent diagnostic vitrectomy in our clinic between January 2000 and November 2013. Reason for vitrectomy was suspected dissemination of tumour cells inside the eye. Treated as well as treatment-naive primary uveal melanomas were included in this study. Follow-up data of all patients were collected. RESULTS: The study included 23 patients with a mean age of 66 years. Four patients presented pigmented vitreous debris at initial presentation prior to treatment of the uveal melanoma. All but one of these four patients has been enucleated as a consequence of cytology-proven vitreous spreading of vital melanoma cells. The remaining 19 patients presented pigmented vitreous debris at a mean of 60 months following local tumour treatment. Thirteen of these patients had been treated with a ruthenium plaque (mean scleral dose 1295 Gy, mean apex dose 152 Gy), three with binuclid plaque (mean scleral dose 1005 Gy, mean apex dose 70 Gy) and three with proton beam radiation. Of the 19 patients, 10 showed only melanophages in the vitreous specimen, while the remaining 9 patients had vital tumour cells in vitreous cytology. Four out of these nine patients have been enucleated in the course of follow-up. During follow-up of our cohort of 23 patients, 4 patients died, but only 1 of them due to metastatic disease. CONCLUSION: The outcome of this small cohort study shows that obtaining a vitreous specimen helps to distinguish melanophages from vital tumour cells. We could not observe an increased risk of metastasis in patients who showed melanoma cell dissemination inside the eye, compared with those patients only showing melanophages. We therefore suggest to carefully re-evaluate the necessity of enucleation in every patient. PMID- 26359337 TI - Genomic correlates of response to CTLA-4 blockade in metastatic melanoma. AB - Monoclonal antibodies directed against cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), such as ipilimumab, yield considerable clinical benefit for patients with metastatic melanoma by inhibiting immune checkpoint activity, but clinical predictors of response to these therapies remain incompletely characterized. To investigate the roles of tumor-specific neoantigens and alterations in the tumor microenvironment in the response to ipilimumab, we analyzed whole exomes from pretreatment melanoma tumor biopsies and matching germline tissue samples from 110 patients. For 40 of these patients, we also obtained and analyzed transcriptome data from the pretreatment tumor samples. Overall mutational load, neoantigen load, and expression of cytolytic markers in the immune microenvironment were significantly associated with clinical benefit. However, no recurrent neoantigen peptide sequences predicted responder patient populations. Thus, detailed integrated molecular characterization of large patient cohorts may be needed to identify robust determinants of response and resistance to immune checkpoint inhibitors. PMID- 26359339 TI - Fifteen years follow-up of photorefractive keratectomy up to 10 D of myopia: outcomes and analysis of the refractive regression. AB - PURPOSE: To evaluate outcomes of photorefractive keratectomy up to -10.00 D of myopia and -4.50 of astigmatism and to develop a predictive model for the refractive changes in the long term. SETTING: Vissum Corporation and Miguel Hernandez University (Alicante, Spain). DESIGN: Retrospective-prospective observational series of cases. METHODS: This study included 33 eyes of 33 patients aged 46.79+/-7.04 years (range 40-57) operated with the VISX 20/20 excimer laser with optical zones of 6 mm. No mitomycin C was used in any of these cases. The minimum follow-up was 15 years. The main outcome measures were: uncorrected and corrected distance visual acuity, manifest refraction and corneal topography. Linear regression models were developed from the observed refractive changes over time. RESULTS: Safety and efficacy indexes at 15 years were 1.18 and 0.83, respectively. No statistically significant differences were detected for any keratometric variable during the follow-up (p>=0.103). 15 years after the surgery 54.55% of the eyes were within +/-1.00 D of spherical equivalent and 84.85% within +/-2.00 D. The uncorrected distance visual acuity at 15 years was 20/25 or better in 60.6% of the eyes and 20/40 or better in 72.73% of the eyes. The correlation between the attempted and the achieved refractions was r=0.948 (p<0.001) at 1 year, and r=0.821 (p<0.001) at 15 years. No corneal ectasia was detected in any case during the follow-up. CONCLUSIONS: Photorefractive keratectomy is a safe refractive procedure in the long term within the range of myopia currently considered suitable for its use, although its efficacy decreases with time, especially, in high myopia. The model developed predicts a myopic regression of 2.00 D at 15 years for an ablation depth of 130 um. PMID- 26359340 TI - The ophthalmic phenotype of IFT140-related ciliopathy ranges from isolated to syndromic congenital retinal dystrophy. AB - BACKGROUND: Conorenal syndrome is a systemic skeletal ciliopathy characterised by skeletal and renal findings and caused by biallelic mutations in the gene intraflagellar transport 140 Chlamydomonas homologue (IFT140). Most studies have focused on syndromic features and are by non-ophthalmologists. We highlight the ophthalmic phenotype. METHODS: Retrospective consecutive case series (2010-2014). RESULTS: Twelve subjects with confirmed homozygous mutations were identified (11 consanguineous families; 7 boys; assessed at age 10 months to 20 years, average and median age 6.5 and 4 years). All were homozygous for the same IFT140 mutation (c.1990G>A; p.Glu664Lys) except one who was homozygous for c.1541_1542delinsAA. All had poor vision and nystagmus since birth, with visual acuity after 5 years old of hand motions or light perception. In early childhood, nine were noted to stare at lights, four were noted to have a happy demeanour, high hyperopia was typical, and electroretinography was non-recordable. Fundus appearance was grossly normal before the age of 1 year but thereafter appeared dystrophic. Eight children had developmental delay, two had short stubby fingers, and one had renal disease, but four had no evident extraocular disease, including one aged 18 years who also had two older affected siblings in their twenties who remained non syndromic and were excelling academically. CONCLUSIONS: Recessive IFT140 mutations cause a severe congenital retinal dystrophy with high hyperopia and often early photophilia. Developmental delay is common but not universal and not all patients have obvious extraocular findings. The c.1990G>A mutation represents a founder effect or mutational hotspot on the Arabian Peninsula. PMID- 26359341 TI - An RCT to Treat Learning Impairment in Traumatic Brain Injury: The TBI-MEM Trial. AB - OBJECTIVE: To examine the efficacy of the modified Story Memory Technique (mSMT) to improve learning (ie, acquisition) and memory in participants with TBI. The mSMT is a behavioral intervention that teaches context and imagery to facilitate learning within 10 sessions over 5 weeks. METHODS: A total of 69 participants with moderate-severe Traumatic Brain Injury (TBI), 35 in the treatment group and 34 in the placebo control group, completed this double-blind, placebo-controlled randomized clinical trial. A baseline neuropsychological assessment was administered, including questionnaires assessing everyday memory. Repeat assessments were conducted immediately posttreatment and 6 months following treatment. Participants in the treatment group were randomly assigned to a booster session or a non-booster session group after completion of treatment with the mSMT to examine the efficacy of monthly booster sessions in facilitating the treatment effect over time. RESULTS: The treatment group demonstrated significant improvement on a prose memory task relative to the placebo group posttreatment (eta(2) = 0.064 medium effect). Similar results were noted on objective measures of everyday memory, specifically prospective memory (Cohen's w = 0.43, medium effect), and family report of disinhibition in daily life (eta(2) = 0.046, medium effect). CONCLUSION: The mSMT is effective for improving learning and memory in TBI. CLASSIFICATION OF EVIDENCE: Based on widely accepted classification systems for treatment study design, this study provides class I evidence that the mSMT behavioral intervention improves both objective memory and everyday memory in persons with TBI over 5 weeks. Thus, this study extends the evidence for efficacy of the treatment protocol to a sample of persons with TBI. PMID- 26359343 TI - Electrical Stimulation to Promote Peripheral Nerve Regeneration. AB - Peripheral nerve injury afflicts individuals from all walks of life. Despite the peripheral nervous system's intrinsic ability to regenerate, many patients experience incomplete functional recovery. Surgical repair aims to expedite this recovery process in the most thorough manner possible. However, full recovery is still rarely seen especially when nerve injury is compounded with polytrauma where surgical repair is delayed. Pharmaceutical strategies supplementary to nerve microsurgery have been investigated but surgery remains the only viable option. Brief low-frequency electrical stimulation of the proximal nerve stump after primary repair has been widely investigated. This article aims to review the currently known biological basis for the regenerative effects of acute brief low-frequency electrical stimulation on axonal regeneration and outline the recent clinical applications of the electrical stimulation protocol to demonstrate the significant translational potential of this modality for repairing peripheral nerve injuries. The review concludes with a discussion of emerging new advancements in this exciting area of research. The current literature indicates the imminent clinical applicability of acute brief low frequency electrical stimulation after surgical repair to effectively promote axonal regeneration as the stimulation has yielded promising evidence to maximize functional recovery in diverse types of peripheral nerve injuries. PMID- 26359342 TI - The Specific Requirements of Neural Repair Trials for Stroke. AB - Novel molecular, cellular, and pharmacological therapies to stimulate repair of sensorimotor circuits after stroke are entering clinical trials. Compared with acute neuroprotection and thrombolysis studies, clinical trials for repair in subacute and chronic hemiplegic participants have a different time course for delivery of an intervention, different mechanisms of action within the milieu of the injury, distinct relationships to the amount of physical activity and skills practice of participants, and need to include more refined outcome measures. This review examines the biological interaction of targeted rehabilitation with neural repair strategies to optimize outcomes. We suggest practical guidelines for the incorporation of inexpensive skills training and exercise at home. In addition, we describe some novel outcome measurement tools, including wearable sensors, to obtain the more detailed outcomes that may identify at least some minimal level of success from cellular and regeneration interventions. Thus, proceeding in the shadow of acute stroke trial designs may unnecessarily limit the mechanisms of action of new repair strategies, reduce their impact on participants, and risk missing important behavioral outcomes. PMID- 26359344 TI - Responsiveness of the Neuromuscular Recovery Scale During Outpatient Activity Dependent Rehabilitation for Spinal Cord Injury. AB - BACKGROUND: The Neuromuscular Recovery Scale (NRS) was developed by researchers and clinicians to functionally classify people with spinal cord injury (SCI) by measuring functionally relevant motor tasks without compensation. Previous studies established strong interrater and test-retest reliability and validity of the scale. OBJECTIVE: To determine responsiveness of the NRS, a version including newly added upper-extremity items, in an outpatient rehabilitation setting. METHODS: Assessments using the NRS and 6 other instruments were conducted at enrollment and discharge from a locomotor training program for 72 outpatients with SCI classified as American Spinal Injury Association Impairment Scale grades A to D (International Standards for Neurological Classification of Spinal Cord Injury). Mixed-model t statistics for instruments were calculated and adjusted for confounding factors (eg, sample size, demographic variables) for all patients and subgroups stratified by injury level and/or severity. The resulting adjusted response means (ARMs) and 95% confidence intervals (CIs) were used to determine responsiveness, and significant differences between instruments were identified with pairwise comparisons. RESULTS: The NRS was significantly responsive for SCI outpatients (ARM = 1.05; CI = 0.75-1.35). Changes in motor function were detected across heterogeneous groups. Regardless of injury level or severity, the responsiveness of the NRS was equal to, and often significantly exceeded, the responsiveness of other instruments. CONCLUSIONS: The NRS is a responsive measure that detects change in motor function during outpatient neurorehabilitation for SCI. There is potential utility for its application in randomized controlled trials and as a measure of clinical recovery across diverse SCI populations. PMID- 26359345 TI - Is Period3 Genotype Associated With Sleep and Recovery in Patients With Disorders of Consciousness? AB - Background Sleep evaluation is increasingly being used as prognostic tool in patients with disorders of consciousness, but, surprisingly, the role of Period3 (Per3) gene polymorphism has never been evaluated. Objective The aim of this study was to investigate the contribution of Per3 genotype on sleep quantity and consciousness recovery level in patients with disorders of consciousness (DOC). Methods In this observational study, we evaluated 71 patients with DOC classified as vegetative state/unresponsive wakefulness syndrome or minimally conscious state. Demographic and clinical data were collected and a standardised diagnostic workup, including a polysomnographic record, was applied. After informed consent provided by proxy, genomic DNA was obtained and Per3 polymorphism was analysed by polymerase chain reaction to identify 5/5, 4/5, or 4/4 genotype. Results Per3(5/5) genotype was found in 12.7% of our DOC patients. The median total Coma Recovery Scale-revised score in Per3(5/5) carriers was significantly higher than 4/4 genotype (10, range 5-16 vs 7, range 4-11; post hoc P = .036). Moreover, total sleep time seemed to be higher in 5/5 genotype (5/5, 221 minutes, range 88 515 minutes; 4/4, 151.5 minutes, range 36-477 minutes; and 4/5, 188 minutes, range 44-422 minutes). Conclusion For the first time we have shown a possible association between Per3 polymorphism and consciousness recovery level in DOC patients. Even though the exact molecular mechanism has not been defined, we speculate that its effect is mediated by higher total sleep time and slow wave sleep, which would improve the preservation of main cerebral connections. PMID- 26359347 TI - Effortless activity tracking with Google Fit. PMID- 26359346 TI - 'Physical Activity 4 Everyone' school-based intervention to prevent decline in adolescent physical activity levels: 12 month (mid-intervention) report on a cluster randomised trial. AB - BACKGROUND: Adolescence is a recognised period of physical activity decline, particularly among low-income communities. We report the 12-month (midpoint) effects of a 2-year multicomponent physical activity intervention implemented in disadvantaged secondary schools. METHODS: A cluster randomised trial was undertaken in 10 secondary schools located in disadvantaged areas in New South Wales, Australia. Students in Grade 7 were recruited, with follow-up in Grade 8. The intervention was guided by socioecological theory and included seven physical activity strategies, and six implementation adoption strategies. The primary outcome was mean minutes of moderate-to-vigorous physical activity (MVPA) per day assessed using Actigraph GT3X accelerometers. Outcome data were analysed using repeated measures linear mixed models. RESULTS: At baseline, 1150 (93%) students participated in the data collection (mean age 12 years, 48% boys) and 1050 (79%) students participated at 12-month follow-up. By the 12-month follow-up, the six implementation adoption strategies had been used to support schools to deliver four of the seven physical activity elements. There was a significant group-by time interaction for mean minutes of MVPA per day in favour of the intervention group (adjusted difference between groups at follow-up=3.85 min, 95% CI (0.79 to 6.91), p <= 0.01), including significantly more vigorous physical activity (2.45 min, p <= 0.01), equating to 27 min more MVPA per week. SUMMARY: At 12-month follow-up, the intervention had reduced the decline in physical activity among adolescents from disadvantaged schools. The intervention may assist students to meet physical activity guidelines. PMID- 26359348 TI - Anomalous Coronary Artery: Run of a Lifetime. AB - The anatomy of the coronary circulation is well described with incidence of congenital anomalies of approximately 0.3% to 1.0%. Although often incidental, 20% are life-threatening. A 25-year-old woman with syncopal episodes collapsed following a 10-km run. Coronary anatomy evaluation showed an anomalous left main coronary artery originating from the right sinus of valsalva and following a course between the aorta and the pulmonary outflow tract. Percutaneous coronary intervention was followed by eventual surgical revascularization. Abnormal course of coronary arteries plays a role in the pathogenesis of sudden death on exertion. Origin of the left main coronary from the right sinus of valsalva is a rare congenital anomaly. The expansion of the roots of the aorta and pulmonary trunk with exertion lead to compression of the coronary artery and syncope. Our patient raises awareness of a potentially fatal coronary artery path. Intraoperative identification of anomalous coronaries by utilizing intraoperative transesophageal echocardiography was critical. PMID- 26359349 TI - Heat shock factor 1, an inhibitor of non-homologous end joining repair. AB - A novel role for HSF1 as an inhibitor of non-homologous end joining (NHEJ) repair activity was identified. HSF1 interacted directly with both of the N-terminal sequences of the Ku70 and Ku86 proteins, which inhibited the endogenous heterodimeric interaction between Ku70 and Ku86. The blocking of the Ku70 and Ku86 interaction by HSF1 induced defective NHEJ repair activity and ultimately activated genomic instability after ionizing radiation (IR), which was similar to effects seen in Ku70 or Ku80 knockout cells. The binding activity between HSF1 and Ku70 or Ku86 was dependent on DNA damage response such as IR exposure, but not on the heat shock mediated transcriptional activation of HSF1. Moreover, the posttranslational modification such as phosphorylation, acetylation and sumoylation of HSF1 did not alter the binding activities of HSF1-Ku70 or HSF1 Ku86. Furthermore, the defect in DNA repair activity by HSF1 was observed regardless of p53 status. Rat mammary tumors derived using dimethylbenz(a)anthracence revealed that high levels of HSF1 expression which correlate with aggressive malignancy, interfered with the binding of Ku70-Ku80. This data suggests that HSF1 interacts with both Ku70 and Ku86 to induce defective NHEJ repair activity and genomic instability, which in turn suggests a novel mechanism of HSF1-mediated cellular carcinogenesis. PMID- 26359350 TI - Acceleration of atherogenesis in ApoE-/- mice exposed to acute or low-dose-rate ionizing radiation. AB - There is epidemiological evidence for increased non-cancer mortality, primarily due to circulatory diseases after radiation exposure above 0.5 Sv. We evaluated the effects of chronic low-dose rate versus acute exposures in a murine model of spontaneous atherogenesis. Female ApoE-/- mice (60 days) were chronically irradiated for 300 days with gamma rays at two different dose rates (1 mGy/day; 20 mGy/day), with total accumulated doses of 0.3 or 6 Gy. For comparison, age matched ApoE-/- females were acutely exposed to the same doses and sacrificed 300 days post-irradiation. Mice acutely exposed to 0.3 or 6 Gy showed increased atherogenesis compared to age-matched controls, and this effect was persistent. When the same doses were delivered at low dose rate over 300 days, we again observed a significant impact on global development of atherosclerosis, although at 0.3 Gy effects were limited to the descending thoracic aorta. Our data suggest that a moderate dose of 0.3 Gy can have persistent detrimental effects on the cardiovascular system, and that a high dose of 6 Gy poses high risks at both high and low dose rates. Our results were clearly nonlinear with dose, suggesting that lower doses may be more damaging than predicted by a linear dose response. PMID- 26359352 TI - N-n-butyl haloperidol iodide protects cardiomyocytes against hypoxia/reoxygenation injury by inhibiting autophagy. AB - N-n-butyl haloperidol iodide (F2), a novel compound derived from haloperidol, protects against the damaging effects of ischemia/reperfusion (I/R) injury in vitro and in vivo. In this study, we hypothesized the myocardial protection of F2 on cardiomyocyte hypoxia/reoxygenation (H/R) injury is mediated by inhibiting autophagy in H9c2 cells. The degree of autophagy by treatment with F2 exposed to H/R in H9c2 cell was characterized by monodansylcadaverine, transmission electron microscopy, and expression of autophagy marker protein LC3. Our results indicated that treatment with F2 inhibited autophagy in H9c2 cells exposed to H/R. 3 methyladenine, an inhibitor of autophagy, suppressed H/R-induced autophagy, and decreased apoptosis, whereas rapamycin, a classical autophagy sensitizer, increased autophagy and apoptosis. Mechanistically, macrophage migration inhibitory factor (MIF) was inhibited by F2 treatment after H/R. Accordingly, small interfering RNA (siRNA)-mediated MIF knockdown decreased H/R-induced autophagy. In summary, F2 protects cardiomyocytes during H/R injury through suppressing autophagy activation. Our results provide a new mechanistic insight into a functional role of F2 against H/R-induced cardiomyocyte injury and death. PMID- 26359351 TI - Adenoid cystic carcinoma: current therapy and potential therapeutic advances based on genomic profiling. AB - Adenoid cystic carcinoma (ACC) is a rare cancer with high potential for recurrence and metastasis. Efficacy of current treatment options, particularly for advanced disease, is very limited. Recent whole genome and exome sequencing has dramatically improved our understanding of ACC pathogenesis. A balanced translocation resulting in the MYB-NFIB fusion gene appears to be a fundamental signature of ACC. In addition, sequencing has identified a number of other driver genes mutated in downstream pathways common to other well-studied cancers. Overexpression of oncogenic proteins involved in cell growth, adhesion, cell cycle regulation, and angiogenesis are also present in ACC. Collectively, studies have identified genes and proteins for targeted, mechanism-based, therapies based on tumor phenotypes, as opposed to nonspecific cytotoxic agents. In addition, although few studies in ACC currently exist, immunotherapy may also hold promise. Better genetic understanding will enable treatment with novel targeted agents and initial exploration of immune-based therapies with the goal of improving outcomes for patients with ACC. PMID- 26359353 TI - NDRG1 promotes growth of hepatocellular carcinoma cells by directly interacting with GSK-3beta and Nur77 to prevent beta-catenin degradation. AB - The N-myc downstream regulated gene 1 (NDRG1) is significantly associated with advanced tumor stages and poor survival of hepatocellular carcinoma (HCC), thereby implicating it as a potential target for HCC treatment. We aim to further understand its biological roles in hepatocarcinogenesis, as a means to exploit it for therapeutic purposes. By screening using the ProtoArray(r) Human Protein Microarrays, we identified glycogen synthase kinase 3beta (GSK-3beta) and the orphan nuclear receptor (Nur77) as potential interaction partners of NDRG1. These interactions were confirmed in HCC cell lines in vitro by co-immunoprecipitation; and co-localizations of NDRG1 with GSK-3beta and Nur77 were observed by immunofluorescence staining. Additionally, high levels of NDRG1 competitively bind to GSK-3beta and Nur77 to allow beta-catenin to escape degradation, with consequent elevated levels of downstream oncogenic genes. In vivo, we consistently observed that NDRG1 suppression in HCC xenografts decreased beta catenin levels and its downstream target Cyclin D1, with concomitant tumor growth inhibition. Clinically, the over-expression of NDRG1 in HCC patient samples is positively correlated with GSK-3beta-9ser (|?? R | = 0.28, p = 0.01), Nur77 (|?? R | = 0.42, p < 0.001), and beta-catenin (| R |= 0.32, p = 0.003) expressions. In conclusion, we identified GSK-3beta and Nur77 as novel interaction partners of NDRG1. These protein-protein interactions regulate the turnover of beta-catenin and subsequent downstream signaling mediated by beta-catenin in HCC cells, and provides potential targets for future therapeutic interventions. PMID- 26359354 TI - Neutrophil-to-lymphocyte ratio predicts prostatic carcinoma in men undergoing needle biopsy. AB - Neutrophil-to-lymphocyte ratio (NLR), a simple marker of systemic inflammatory response, has been demonstrated as an independent prognosticator for some solid malignancies, including prostate cancer. In the present study, we evaluated the role of NLR in men who underwent prostate needle biopsy for their initial diagnosis of prostatic carcinoma. Both complete blood counts and free/total (F/T) prostate-specific antigen (PSA) ratio were examined in a total of 3,011 men in our institution. Of these, 1,207 had a PSA level between 4 and 10 ng/mL, and 357 of 810 who subsequently underwent prostate needle biopsy were found to have prostatic adenocarcinoma. NLR value was significantly higher in men with PSA of >= 20 ng/mL than in those with PSA of < 20 ng/mL (p < 0.001). NLR was also significantly higher in men with positive biopsy than in those with negative biopsy (p < 0.001). Using NLR cut-off point of 2.40 determined by the AUROC curve, positive/negative predictive values of NLR alone and NLR combined with F/T PSA ratio (cut-off: 0.15) were 56.6%/60.8% and 80.7%/60.1%, respectively. Multivariate analysis revealed that not only F/T PSA ratio (HR = 3.13) but also NLR (HR = 2.21) was an independent risk factor for prostate cancer. NLR is thus likely elevated in patients with prostate cancer. Accordingly, NLR, with or without combination with F/T PSA ratio, may function as a new biomarker to predict prostate cancer in men undergoing prostate needle biopsy. PMID- 26359355 TI - Indocyanine Green: Historical Context, Current Applications, and Future Considerations. AB - BACKGROUND: Indocyanine green (ICG) is a dye used in medicine since the mid-1950s for a variety of applications in in cardiology, ophthalmology, and neurosurgery; however, its fluorescent properties have only recently been used in the intraoperative evaluation of tissue perfusion. METHOD: A literature review was conducted on the characterization and employment of ICG within the medical field. Historical and current context of ICG was examined while also considering implications for its future use. RESULTS: ICG is a relatively nontoxic, unstable compound bound by albumin in the intravascular space until rapid clearance by the liver. It has widespread uses in hepatic, cardiac, and ophthalmologic studies, and its use in analyzing tissue perfusion and identifying sentinel lymph nodes in cancer staging is gaining popularity. CONCLUSIONS: ICG has myriad applications and poses low risk to the patient. Its historical uses have contributed to medical knowledge, and it is now undergoing investigation for quantifying tissue perfusion, providing targeted therapies, and intraoperative identification of neurovascular anatomy, ophthalmic structures, and sentinel lymph nodes. New applications of ICG may lead to reduction in postoperative wound-related complications, more effective ophthalmologic procedures, and better detection and treatment of cancer cells. PMID- 26359356 TI - An integrative approach for the identification of prognostic and predictive biomarkers in rectal cancer. AB - INTRODUCTION: Colorectal cancer is the third most common cancer in the world, a small fraction of which is represented by locally advanced rectal cancer (LARC). If not medically contraindicated, preoperative chemoradiotherapy, represent the standard of care for LARC patients. Unfortunately, patients shows a wide range of response rates in which approximately 20% has a complete pathological response, whereas in 20 to 40% the response is poor or absent. RESULTS: The following specific gene signature, able to discriminate responders' patients from non responders, were founded: AKR1C3, CXCL11, CXCL10, IDO1, CXCL9, MMP12 and HLA-DRA. These genes are mainly involved in immune system pathways and interact with drugs traditionally used in the adjuvant treatment of rectal cancer. DISCUSSION: The present study suggests that new ideas for therapy could be found not only limited to studying genes differentially expressed between the two groups of patients but deepening the mechanisms, associated to response, in which they are involved. METHODS: Gene expression studies performed by: Agostini et al., Rimkus et al. and Kim et al. have been merged through a meta-analysis of the raw data. Gene expression data-sets have been processed using A-MADMAN. Common differentially expressed gene (DEG) were identified through SAM analysis. To further characterize the identified DEG we deeply investigated its biological role using an integrative computational biology approach. PMID- 26359357 TI - Cyclooxygenase-2 in tumor-associated macrophages promotes breast cancer cell survival by triggering a positive-feedback loop between macrophages and cancer cells. AB - Tumor-associated macrophages (TAMs) play an important role in cancer cell survival, however, the mechanism of which remains elusive. In this study, we found that COX-2 was abundantly expressed in breast TAMs, which was correlated to poor prognosis in breast cancer patients. Ectopic over-expression of COX-2 in TAMs enhanced breast cancer cell survival both in vitro and in vivo. COX-2 in TAMs was determined to be essential for the induction and maintenance of M2 phenotype macrophage polarity. COX-2(+) TAMs promoted breast cancer cell proliferation and survival by increasing Bcl-2 and P-gp and decreasing Bax in cancer cells. Furthermore, COX-2 in TAMs induced the expression of COX-2 in breast cancer cells, which in turn promoted M2 macrophage polarization. Inhibiting PI3K/Akt pathway in cancer cells suppressed COX-2(+) TAMs-induced cancer cell survival. These findings suggest that COX-2, functions as a key cancer promoting factor by triggering a positive-feedback loop between macrophages and cancer cells, which could be exploited for breast cancer prevention and therapy. PMID- 26359358 TI - Honokiol activates LKB1-miR-34a axis and antagonizes the oncogenic actions of leptin in breast cancer. AB - Leptin, a major adipocytokine produced by adipocytes, is emerging as a key molecule linking obesity with breast cancer therefore, it is important to find effective strategies to antagonize oncogenic effects of leptin to disrupt obesity cancer axis. Here, we examine the potential of honokiol (HNK), a bioactive polyphenol from Magnolia grandiflora, as a leptin-antagonist and systematically elucidate the underlying mechanisms. HNK inhibits leptin-induced epithelial mesenchymal-transition (EMT), and mammosphere-formation along with a reduction in the expression of stemness factors, Oct4 and Nanog. Investigating the downstream mediator(s), that direct leptin-antagonist actions of HNK; we discovered functional interactions between HNK, LKB1 and miR-34a. HNK increases the expression and cytoplasmic-localization of LKB1 while HNK-induced SIRT1/3 accentuates the cytoplasmic-localization of LKB1. We found that HNK increases miR 34a in LKB1-dependent manner as LKB1-silencing impedes HNK-induced miR-34a which can be rescued by LKB1-overexpression. Finally, an integral role of miR-34a is discovered as miR-34a mimic potentiates HNK-mediated inhibition of EMT, Zeb1 expression and nuclear-localization, mammosphere-formation, and expression of stemness factors. Leptin-antagonist actions of HNK are further enhanced by miR 34a mimic whereas miR-34a inhibitor results in inhibiting HNK's effect on leptin. These data provide evidence for the leptin-antagonist potential of HNK and reveal the involvement of LKB1 and miR-34a. PMID- 26359360 TI - National Institutes of Health Stroke Scale Item Profiles as Predictor of Patient Outcome: External Validation on Safe Implementation of Thrombolysis in Stroke Monitoring Study Data. AB - BACKGROUND AND PURPOSE: National Institutes of Health Stroke Scale (NIHSS) item profiles that were recently proposed and validated may prove useful for clinical prognostication and research studies. We aimed to validate the NIHSS item profiles in hyper-acute stroke patients who received thrombolysis treatment (tissue-type plasminogen activator). METHODS: We applied the latent class analysis probabilities of the profile membership generated from the derivation study onto NIHSS data from the Safe Implementation of Thrombolysis in Stroke Monitoring Study (SITS-MOST). We separately considered NIHSS data collected within 3 hours and at ~24 hours after stroke onset to obtain 2 sets of symptom groupings. The discrimination and calibration of both sets of symptom profiles were assessed from their association with outcomes. The outcome measures included modified Rankin Scale (mRS; using full distribution and dichotomized, mRS 0-1 or back to baseline) at day 90 and mortality by 90 days. RESULTS: We obtained data for 6843 patients. Ordinal analysis of mRS showed odds of better outcome across the profiles, for each set of symptom profiles, adjusted for age, sex, and prestroke mRS. Dichotomized outcomes mirrored the ordinal findings. There were significant differences in prognostic discrimination ability for the dichotomized outcome measures between the 2 sets of symptom profiles, with the latter set (ie, 24-hour symptom profiles) performing better. CONCLUSIONS: The NIHSS item profiles are individually associated with functional outcome and mortality in acute stroke patients treated with tissue-type plasminogen activator. Considering profiles of NIHSS subscores rather than only the total score is informative for prognostication, particularly for assessments collected 24 hours after stroke onset. PMID- 26359359 TI - All-trans retinoic acid and rapamycin normalize Hutchinson Gilford progeria fibroblast phenotype. AB - Hutchinson Gilford progeria syndrome is a fatal disorder characterized by accelerated aging, bone resorption and atherosclerosis, caused by a LMNA mutation which produces progerin, a mutant lamin A precursor. Progeria cells display progerin and prelamin A nuclear accumulation, altered histone methylation pattern, heterochromatin loss, increased DNA damage and cell cycle alterations. Since the LMNA promoter contains a retinoic acid responsive element, we investigated if all-trans retinoic acid administration could lower progerin levels in cultured fibroblasts. We also evaluated the effect of associating rapamycin, which induces autophagic degradation of progerin and prelamin A. We demonstrate that all-trans retinoic acid acts synergistically with low-dosage rapamycin reducing progerin and prelamin A, via transcriptional downregulation associated with protein degradation, and increasing the lamin A to progerin ratio. These effects rescue cell dynamics and cellular proliferation through recovery of DNA damage response factor PARP1 and chromatin-associated nuclear envelope proteins LAP2alpha and BAF. The combined all-trans retinoic acid rapamycin treatment is dramatically efficient, highly reproducible, represents a promising new approach in Hutchinson-Gilford Progeria therapy and deserves investigation in ageing-associated disorders. PMID- 26359361 TI - Management of Central Poststroke Pain: Systematic Review of Randomized Controlled Trials. AB - BACKGROUND AND PURPOSE: Central poststroke pain is a chronic neuropathic disorder that follows a stroke. Current research on its management is limited, and no review has evaluated all therapies for central poststroke pain. METHODS: We conducted a systematic review of randomized controlled trials to evaluate therapies for central poststroke pain. We identified eligible trials, in any language, by systematic searches of AMED, CENTRAL, CINAHL, DARE, EMBASE, HealthSTAR, MEDLINE, and PsychINFO. Eligible trials (1) enrolled >=10 patients with central poststroke pain; (2) randomly assigned them to an active therapy or a control arm; and (3) collected outcome data>=14 days after treatment. Pairs of reviewers, independently and in duplicate, screened titles and abstracts of identified citations, reviewed full texts of potentially eligible trials, and extracted information from eligible studies. We used a modified Cochrane tool to evaluate risk of bias of eligible studies, and collected patient-important outcomes according to recommendations by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials. We conducted, when possible, random effects meta-analyses, and evaluated our certainty in treatment effects using the Grading of Recommendations Assessment, Development, and Evaluation System. RESULTS: Eight eligible English language randomized controlled trials (459 patients) tested anticonvulsants, an antidepressant, an opioid antagonist, repetitive transcranial magnetic stimulation, and acupuncture. Results suggested that all therapies had little to no effect on pain and other patient-important outcomes. Our certainty in the treatment estimates ranged from very low to low. CONCLUSIONS: Our findings are inconsistent with major clinical practice guidelines; the available evidence suggests no beneficial effects of any therapies that researchers have evaluated in randomized controlled trials. PMID- 26359362 TI - Trends in Stroke Incidence and 28-Day Case Fatality in a Nationwide Stroke Registry of a Multiethnic Asian Population. AB - BACKGROUND AND PURPOSE: This study investigated trends in stroke incidence and case fatality overall and according to sex, age, ethnicity, and stroke subtype in a multiethnic Asian population. METHODS: The Singapore Stroke Registry identifies all stroke cases in all public hospitals using medical claims, hospital discharge summaries, and death registry data. Age-standardized incidence rates and 28-day case-fatality rates were calculated for individuals aged >=15 years between 2006 and 2012. To estimate the annual percentage change of the rates, a linear regression model was fitted to the log rates, and a Wald test was performed to test for trend. P values <0.05 were considered significant. RESULTS: A total of 40 623 cases were recorded. The total stroke incidence fell by ~12.0%, and case fatality fell by 17.2% in the study. Declining trends in stroke incidence were stronger in women (female: -2.94; 95% confidence interval [CI], -3.43 to -2.44; male: -1.80; 95% CI, -2.58 to -1.02); in the older age groups (>=65 years: -3.62; 95% CI, -4.30 to -2.94; 50-64 years: -1.26; 95% CI, -1.97 to -0.55; <50 years: 3.33; 95% CI, 1.49 to 5.20), in Chinese (-2.64; 95% CI, -3.15 to -2.13), Indians (-3.78; 95% CI, -5.93 to -1.58), and others (-12.73; 95% CI, -18.93 to -6.06) compared with Malays (2.58; 95% CI, 1.17 to 4.02); and in ischemic stroke subtype (ischemic: -2.43; 95% CI, -3.13 to -1.73; hemorrhagic: -1.02; 95% CI, -2.04 to 0.01). Subgroup-specific findings for case fatality were similar. CONCLUSION: This is the first countrywide hospital-based registry study in a multiethnic Asian population, and it revealed marked overall reductions in stroke incidence and case fatality. However, it also identified important population groups with less favorable trends, especially younger adults and those of Malay ethnicity. PMID- 26359363 TI - Metformin represses cancer cells via alternate pathways in N-cadherin expressing vs. N-cadherin deficient cells. AB - Metformin has emerged as a potential anticancer agent. Here, we demonstrate that metformin plays an anti-tumor role via repressing N-cadherin, independent of AMPK, in wild-type N-cadherin cancer cells. Ectopic-expression of N-cadherin develops metformin-resistant cancer cells, while suppression of N-cadherin sensitizes cancer to metformin. Manipulation of AMPK expression does not alter sensitivity of cancer to metformin. We show that NF-kappaB is a downstream molecule of N-cadherin and metformin regulates NF-kappaB signaling via suppressing N-cadherin. Moreover, we also suggest that TWIST1 is an upstream molecule of N-cadherin/NF-kappaB signaling and manipulation of TWIST1 expression changes the sensitivity of cancer cells to metformin. In contrast to the cells that express N-cadherin, in N-cadherin deficient cells, metformin plays an anti tumor role via activation of AMPK. Ectopic expression of N-cadherin makes cancer more resistant to metformin. Therefore, we suggest that metformin's anti-cancer therapeutic effect is mediated through different molecular mechanism in wild-type vs. deficient N-cadherin cancer cells. At last, we selected 49 out of 984 patients' samples with prostatic cancer after radical prostatectomy (selection criteria: Gleason score >= 7 and all patients taking metformin) and showed levels of N-cadherin, p65 and AMPK could predict post-surgical recurrence in prostate cancer after treatment of metformin. PMID- 26359369 TI - Correction for Dreux et al., Ribonucleotide Reductase Repressor NrdR as a Novel Regulator for Motility and Chemotaxis during Adherent-Invasive Escherichia coli Infection. PMID- 26359370 TI - Correction for Blondel et al., The Type VI Secretion System Encoded in Salmonella Pathogenicity Island 19 Is Required for Salmonella enterica Serotype Gallinarum Survival within Infected Macrophages. PMID- 26359368 TI - NF2 Loss Promotes Oncogenic RAS-Induced Thyroid Cancers via YAP-Dependent Transactivation of RAS Proteins and Sensitizes Them to MEK Inhibition. AB - Ch22q LOH is preferentially associated with RAS mutations in papillary and in poorly differentiated thyroid cancer (PDTC). The 22q tumor suppressor NF2, encoding merlin, is implicated in this interaction because of its frequent loss of function in human thyroid cancer cell lines. Nf2 deletion or Hras mutation is insufficient for transformation, whereas their combined disruption leads to murine PDTC with increased MAPK signaling. Merlin loss induces RAS signaling in part through inactivation of Hippo, which activates a YAP-TEAD transcriptional program. We find that the three RAS genes are themselves YAP-TEAD1 transcriptional targets, providing a novel mechanism of promotion of RAS-induced tumorigenesis. Moreover, pharmacologic disruption of YAP-TEAD with verteporfin blocks RAS transcription and signaling and inhibits cell growth. The increased MAPK output generated by NF2 loss in RAS-mutant cancers may inform therapeutic strategies, as it generates greater dependency on the MAPK pathway for viability. SIGNIFICANCE: Intensification of mutant RAS signaling through copy-number imbalances is commonly associated with transformation. We show that NF2/merlin inactivation augments mutant RAS signaling by promoting YAP/TEAD-driven transcription of oncogenic and wild-type RAS, resulting in greater MAPK output and increased sensitivity to MEK inhibitors. PMID- 26359372 TI - Aberrant expression and activity of histone deacetylases in sporadic idiopathic pulmonary fibrosis. AB - BACKGROUND: Activation and differentiation of fibroblasts into contractile protein-expressing myofibroblasts and their acquired apoptosis-resistant phenotype are critical factors towards the development of idiopathic pulmonary fibrosis (IPF), a fatal disease characterised by distorted pulmonary structure and excessive extracellular matrix (ECM) deposition. The molecular mechanisms underlying these processes in IPF remain incompletely understood. We investigated the possible implication of aberrant overexpression and activity of histone deacetylases (HDACs) in IPF. METHODS: We analysed lung tissues from patients with sporadic IPF (n=26) and non-diseased control lungs (n=16) for expression of class I and II HDACs. Primary IPF fibroblasts were treated with HDAC inhibitors (HDACi) LBH589 or valproic acid (VPA). RESULTS: Compared to control lungs, protein levels of class I (HDAC1, HDAC2, HDAC3, HDAC8) and class II HDACs (HDAC4, HDAC 5, HDAC 7, HDAC 9) were significantly elevated in IPF lungs. Using immunohistochemistry, strong induction of nearly all HDAC enzymes was observed in myofibroblasts of fibroblast foci and in abnormal bronchiolar basal cells at sites of aberrant re epithelialisation in IPF lungs, but not in controls. Treatment of primary IPF fibroblasts with the pan-HDACi LBH589 resulted in significantly reduced expression of genes associated with ECM synthesis, proliferation and cell survival, as well as in suppression of HDAC7, and was paralleled by induction of endoplasmic reticulum stress and apoptosis. The profibrotic and apoptosis resistant phenotype of IPF fibroblasts was also partly attenuated by the class I HDACi VPA. CONCLUSIONS: Aberrant overexpression of HDACs in basal cells of IPF lungs may contribute to the bronchiolisation process in this disease. Similarly, generation and apoptosis resistance of IPF fibroblasts are mediated by enhanced activity of HDAC enzymes. Therefore, pan-HDAC inhibition by LBH589 may present a novel therapeutic option for patients with IPF. PMID- 26359375 TI - A novel exon in the human Ca2+-activated Cl- channel Ano1 imparts greater sensitivity to intracellular Ca2. AB - Anoctamin 1 (Ano1; TMEM16A) is a Ca(2+)-activated Cl(-) channel (CACC) expressed in interstitial cells of Cajal. The mechanisms by which Ca(2+) regulates Ano1 are incompletely understood. In the gastrointestinal tract, Ano1 is required for normal slow wave activity and is involved in regulating cell proliferation. Splice variants of Ano1 have varying electrophysiological properties and altered expression in disease states. Recently, we identified a transcript for human Ano1 containing a novel exon-"exon 0" upstream of and in frame with exon 1. The electrophysiological properties of this longer Ano1 isoform are unknown. Our aim was to determine the functional contribution of the newly identified exon to the Ca(2+) sensitivity and electrophysiological properties of Ano1. Constructs with [Ano1(+0)] or without [Ano1(-0)] the newly identified exon were transfected into human embryonic kidney-293 cells. Voltage-clamp electrophysiology was used to determine voltage- and time-dependent parameters of whole cell Cl(-) currents between isoforms with varying concentrations of intracellular Ca(2+), extracellular anions, or Cl(-) channel inhibitors. We found that exon 0 did not change voltage sensitivity and had no impact on the relative permeability of Ano1 to most anions. Ano1(+0) exhibited greater changes in current density but lesser changes in kinetics than Ano1(-0) in response to varying intracellular Ca(2+). The CACC inhibitor niflumic acid inhibited current with greater efficacy and higher potency against Ano1(+0) compared with Ano1(-0). Likewise, the Ano1 inhibitor T16Ainh-A01 reduced Ano1(+0) more than Ano1(-0). In conclusion, human Ano1 containing exon 0 imparts its Cl(-) current with greater sensitivity to intracellular Ca(2+) and CACC inhibitors. PMID- 26359376 TI - Young Athletes With Quadriceps Femoris Strength Asymmetry at Return to Sport After Anterior Cruciate Ligament Reconstruction Demonstrate Asymmetric Single-Leg Drop-Landing Mechanics. AB - BACKGROUND: Young athletes who have had anterior cruciate ligament (ACL) reconstruction demonstrate suboptimal rates of return to sport, high rates of second ACL injuries, and persistent movement asymmetries. Therefore, the influence of musculoskeletal impairments on movement mechanics in this population needs to be further evaluated. HYPOTHESIS: The primary hypothesis was that among young athletes who have had ACL reconstruction, those with greater quadriceps strength asymmetry would demonstrate altered single-leg drop-landing mechanics at return to sport compared with individuals with more symmetric quadriceps strength and also compared with healthy controls (ie, those with no ACL reconstruction). A second hypothesis was that quadriceps strength symmetry would predict single-leg drop-landing symmetry in individuals who have undergone ACL reconstruction. STUDY DESIGN: Controlled laboratory study. METHODS: The study entailed a total of 103 participants (age, 17.4 years) at the time of return to sport after ACL reconstruction and 47 control participants (age, 17.0 years). The quadriceps index (QI) was calculated for isometric quadriceps strength, which was then used to divide the ACL reconstruction participants into high-quadriceps (QI >=90%; n = 52) and low-quadriceps (QI <85%; n = 41) subgroups. Biomechanical data were collected by use of 3-dimensional motion analysis during a single-leg drop landing task. The LSI was calculated for kinematic and kinetic sagittal-plane variables of interest during landing. Group differences were compared by use of 1 way analysis of variance and linear regression analyses (alpha < .05). RESULTS: Both the low- and high-quadriceps groups demonstrated greater limb asymmetry during landing compared with the control group in knee flexion excursion (mean LSI +/- SD: low quadriceps, 85.8% +/- 15.5% [P < .001]; high quadriceps, 94.2% +/ 15.6% [P = .019]; control, 102.7% +/- 14.1%), peak trunk flexion angle (low quadriceps, 129.2% +/- 36.6% [P < .001]; high quadriceps, 110.5% +/- 22.6% [P = .03]; control, 95.5% +/- 26.2%), and peak knee extension moment (low quadriceps, 79.5% +/- 25.2% [P < .001]; high quadriceps, 89.9% +/- 19.8% [P = .005]; control, 102.2% +/- 10.9%). Compared with the high-quadriceps group, the low-quadriceps group also demonstrated greater asymmetry during landing in knee flexion excursion (P = .026), peak trunk flexion angle (P = .006), and peak knee extension moment (P = .034). In the ACL reconstruction group, quadriceps strength symmetry predicted symmetry in knee flexion excursion, peak trunk flexion, and peak knee extension moment (all P < .001) and predicted symmetry in peak trunk flexion angle (P < .001) after controlling for graft type, knee-related pain, function with activities of daily living, and sport function. CONCLUSION: At the time of return to sport, athletes who had undergone ACL reconstruction, including those in both the high- and low-quadriceps groups, demonstrated asymmetry during a single-leg drop-landing task compared with controls. Compensations included increased trunk flexion, decreased knee flexion excursion, and decreased knee extension moments on the involved limb. In addition, individuals in the low quadriceps group demonstrated greater movement asymmetry compared with individuals in the high-quadriceps group. CLINICAL RELEVANCE: Restoration of symmetric quadriceps strength after ACL reconstruction is associated with more symmetric mechanics during a single-leg drop-landing movement. However, this appears to be multifactorial, as the high-quadriceps group also demonstrated landing asymmetries. Restoration of symmetric quadriceps strength may improve postoperative athletic participation; however, future study is warranted. PMID- 26359377 TI - Puerto Rico's future at stake. PMID- 26359379 TI - PALEOANTHROPOLOGY. New human species discovered. PMID- 26359380 TI - MEDICAL NANOTECHNOLOGY. Spherical nucleic acids start rolling. PMID- 26359381 TI - CLIMATE CHANGE. A cold, creeping menace. PMID- 26359382 TI - BIOSECURITY. Flu study raises questions about U.S. ban. PMID- 26359383 TI - Global payer. PMID- 26359384 TI - Tailpipe to tank. PMID- 26359385 TI - Conjuring chemical cornucopias out of thin air. PMID- 26359386 TI - GEOPHYSICS. Weak subduction makes great quakes. PMID- 26359387 TI - EVOLUTION. How single cells work together. PMID- 26359388 TI - CLIMATE. An increasing carbon sink? PMID- 26359389 TI - IMMUNOLOGY. Viruses carry antiviral cargo. PMID- 26359390 TI - PLANT BIOCHEMISTRY. Fighting cancer while saving the mayapple. PMID- 26359391 TI - QUANTUM MECHANICS. Interference of atomic clocks. PMID- 26359392 TI - CLIMATE CHANGE. Winning coalitions for climate policy. PMID- 26359393 TI - MICROBIOME. Rethinking heritability of the microbiome. PMID- 26359394 TI - Commercial forests: Native advantage. PMID- 26359395 TI - Bringing science to prisons is not enough. PMID- 26359396 TI - Illuminating next steps for NEON. PMID- 26359397 TI - Coherent manipulation of Andreev states in superconducting atomic contacts. AB - Coherent control of quantum states has been demonstrated in a variety of superconducting devices. In all of these devices, the variables that are manipulated are collective electromagnetic degrees of freedom: charge, superconducting phase, or flux. Here we demonstrate the coherent manipulation of a quantum system based on Andreev bound states, which are microscopic quasi particle states inherent to superconducting weak links. Using a circuit quantum electrodynamics setup, we performed single-shot readout of this Andreev qubit. We determined its excited-state lifetime and coherence time to be in the microsecond range. Quantum jumps and parity switchings were observed in continuous measurements. In addition to having possible quantum information applications, such Andreev qubits are a test-bed for the physics of single elementary excitations in superconductors. PMID- 26359398 TI - Critical behavior at a dynamic vortex insulator-to-metal transition. AB - An array of superconducting islands placed on a normal metal film offers a tunable realization of nanopatterned superconductivity. This system enables investigation of the nature of competing vortex states and phase transitions between them. A square array creates the eggcrate potential in which magnetic field-induced vortices are frozen into a vortex insulator. We observed a vortex insulator-vortex metal transition driven by the applied electric current and determined critical exponents that coincided with those for thermodynamic liquid gas transition. Our findings offer a comprehensive description of dynamic critical behavior and establish a deep connection between equilibrium and nonequilibrium phase transitions. PMID- 26359399 TI - Stress orientations in subduction zones and the strength of subduction megathrust faults. AB - Subduction zone megathrust faults produce most of the world's largest earthquakes. Although the physical properties of these faults are difficult to observe directly, their frictional strength can be estimated indirectly by constraining the orientations of the stresses that act on them. A global investigation of stress orientations in subduction zones finds that the maximum compressive stress axis plunges systematically trenchward, consistently making an angle of 45 degrees to 60 degrees with respect to the subduction megathrust fault. These angles indicate that the megathrust fault is not substantially weaker than its surroundings. Together with several other lines of evidence, this implies that subduction zone megathrusts are weak faults in a low-stress environment. The deforming outer accretionary wedge may decouple the stress state along the megathrust from the constraints of the free surface. PMID- 26359400 TI - Tuning of fast-spiking interneuron properties by an activity-dependent transcriptional switch. AB - The function of neural circuits depends on the generation of specific classes of neurons. Neural identity is typically established near the time when neurons exit the cell cycle to become postmitotic cells, and it is generally accepted that, once the identity of a neuron has been established, its fate is maintained throughout life. Here, we show that network activity dynamically modulates the properties of fast-spiking (FS) interneurons through the postmitotic expression of the transcriptional regulator Er81. In the adult cortex, Er81 protein levels define a spectrum of FS basket cells with different properties, whose relative proportions are, however, continuously adjusted in response to neuronal activity. Our findings therefore suggest that interneuron properties are malleable in the adult cortex, at least to a certain extent. PMID- 26359401 TI - The reinvigoration of the Southern Ocean carbon sink. AB - Several studies have suggested that the carbon sink in the Southern Ocean-the ocean's strongest region for the uptake of anthropogenic CO2 -has weakened in recent decades. We demonstrated, on the basis of multidecadal analyses of surface ocean CO2 observations, that this weakening trend stopped around 2002, and by 2012, the Southern Ocean had regained its expected strength based on the growth of atmospheric CO2. All three Southern Ocean sectors have contributed to this reinvigoration of the carbon sink, yet differences in the processes between sectors exist, related to a tendency toward a zonally more asymmetric atmospheric circulation. The large decadal variations in the Southern Ocean carbon sink suggest a rather dynamic ocean carbon cycle that varies more in time than previously recognized. PMID- 26359402 TI - Six enzymes from mayapple that complete the biosynthetic pathway to the etoposide aglycone. AB - Podophyllotoxin is the natural product precursor of the chemotherapeutic etoposide, yet only part of its biosynthetic pathway is known. We used transcriptome mining in Podophyllum hexandrum (mayapple) to identify biosynthetic genes in the podophyllotoxin pathway. We selected 29 candidate genes to combinatorially express in Nicotiana benthamiana (tobacco) and identified six pathway enzymes, including an oxoglutarate-dependent dioxygenase that closes the core cyclohexane ring of the aryltetralin scaffold. By coexpressing 10 genes in tobacco-these 6 plus 4 previously discovered-we reconstitute the pathway to (-) 4'-desmethylepipodophyllotoxin (the etoposide aglycone), a naturally occurring lignan that is the immediate precursor of etoposide and, unlike podophyllotoxin, a potent topoisomerase inhibitor. Our results enable production of the etoposide aglycone in tobacco and circumvent the need for cultivation of mayapple and semisynthetic epimerization and demethylation of podophyllotoxin. PMID- 26359403 TI - The inner centromere-shugoshin network prevents chromosomal instability. AB - Chromosomal instability (CIN) is a major trait of cancer cells and a potent driver of tumor progression. However, the molecular mechanisms underlying CIN still remain elusive. We found that a number of CIN(+) cell lines have impairments in the integrity of the conserved inner centromere-shugoshin (ICS) network, which coordinates sister chromatid cohesion and kinetochore-microtubule attachment. These defects are caused mostly by the loss of histone H3 lysine 9 trimethylation at centromeres and sometimes by a reduction in chromatin associated cohesin; both pathways separately sustain centromeric shugoshin stability. Artificial restoration of the ICS network suppresses chromosome segregation errors in a wide range of CIN(+) cells, including RB- and BRCA1 deficient cells. Thus, dysfunction of the ICS network might be a key mechanism underlying CIN in human tumorigenesis. PMID- 26359405 TI - Erratum for the Review "Plant and animal sensors of conserved microbial signatures" by P. C. Ronald and B. Beutler. PMID- 26359404 TI - Nice to know you. PMID- 26359406 TI - A Mobile Alert System for Preparing the Delivery of Radiation Mitigators. AB - BACKGROUND/AIM: A mobile system allowing hospital medical personnel to prepare for the administration of radiation mitigators prior to receiving casualties is desirable. MATERIALS AND METHODS: We evaluated a portable spectroscopic personal radiation detector for use as an ambulance-based unit for early detection and identification of gamma radiation. We tested the sensitivity, time-to identification, and radionuclide identification accuracy rates, change in detector response to vehicle operation, interference from cardiac equipment, and internal versus external radiation source location. RESULTS: We detected radiation sources in each of 119 trials using a humanoid phantom in a moving ambulance with a primary radionuclide identification accuracy of 96%. Typical identification time was around two minutes (149+/-95 s). CONCLUSION: Our observations suggest this mobile system is a potential pre-hospital arrival tool allowing for rapid preparation of radiation mitigators. PMID- 26359407 TI - Aortic Valve Endocarditis Caused by Abiotrophia defectiva: Case Report and Literature Overview. AB - Abiotrophia defectiva or nutritionally variant Streptococcus (NVS) are a rare but important cause of infectious endocarditis, with high rates of bacteriological failure and mortality. We report the case of a 74-year-old man admitted for fever, fatigue and general malaise in the absence of any underlying cardiac, immunosuppressive illness and previous dental manipulations. Transthoracic and transesophageal echocardiogram revealed bacterial vegetation and significant aortic stenosis and regurgitation. Initial blood culture reported gram-positive cocci in chains, subsequently identified as A. defectiva. The patient completed 6 weeks of antibiotic therapy with ampicillin, with a significant decrease of serum inflammatory markers. He refused cardiac surgery and had relapsing endocarditis with positive blood culture for the same pathogen. The patient was then submitted to double-valve cardiac surgery, obtaining a prompt resolution of clinical signs and symptoms, without other relapse or any complications. CONCLUSION: Infectious diseases caused by A. defectiva are extremely rare illnesses. Due to the difficult isolation of the pathogen and the slow clinical progression, clinicians should be aware of this bacterium when dealing with blood culture-negative infective endocarditis. PMID- 26359408 TI - Influence of Fetal Birth Weight on Caesarean Section Rate and Fetal Outcome After Induction of Labor. AB - AIM: The aim of the present study was to provide information for better obstetric counselling by analyzing the impact of fetal birth weight on the caesarean section rate and fetal outcome after induction of labor. MATERIALS AND METHODS: In this retrospective study from January 2010 to December 2013, 1,474 singleton deliveries with labor induction at or greater than 37 gestational weeks were analyzed for their impact of fetal birth weight on delivery outcome. The normal birth weight group was defined as 2,500 g to less than 4,000 g. For comparison, further birth weight groups were defined as: group 1 <2,500 g, group 2 4,000 to <4,250 g; group 3 >=4,250 g. The primary outcome was the caesarean section rate; secondary outcome measures were fetal complications monitored by pH and base excess (BE) of the umbilical cord artery, Apgar score after 5 min (Apgar-5) and postpartum transfer to the Neonatal Care Unit. The set of controlling variables included maternal body mass index and age, gestational age, neonatal sex, maternal diabetes, maternal hypertension disorder, parity and method of induction of labor. RESULTS: Second-stage caesarean section is significantly more likely when fetal birth weight is below 2,500 g (42.9% vs. 24.2% in the normal birth weight group, odds ratio=3.11, 95% confidence interval=1.48-6.51, p=0.003). A birth weight of 4,000 g or more did not have a significant influence on the caesarean section rate. Only the mean Apgar-5 for group 1 was significantly lower (p=0.044). The non-parametric tests and regression analyzes of pH and BE of the umbilical cord and of the Apgar-5 for adverse fetal outcome (pH<7.05, BE<-12 or Apgar-5 <7) showed no significant differences in the three birth weight groups when compared to the normal group. Neonates were significantly more often transferred to the Neonatal Care Unit after delivery when birth weight was below 2,500 g (odds ratio=9.68, 95% confidence interval=4.33-21.65, p<0.001) or above 4,250 g (odds ratio=2.68, 95% confidence interval=1.34-5.36, p=0.005). CONCLUSION: Although a fetal birth weight of under 2500 g and a birth weight over 4,250 g are associated with some risks, there is no general contraindication against performing induction of labor in regards to fetal birth weight. PMID- 26359409 TI - Predicting Survival After Irradiation for Brain Metastases from Head and Neck Cancer. AB - AIM: Patients with cerebral metastases from head and neck cancer are not common. This study aimed to create an instrument for estimating survival in this particular group of patients. PATIENTS AND METHODS: Survival was significantly influenced by Eastern Cooperative Oncology Group (ECOG) performance score, number of cerebral lesions and extracranial metastatic disease. These characteristics were included in our score. RESULTS: Scoring was based on 6-month survival data: ECOG 0-1=1 point, ECOG 2-3=0 points, 1-3 cerebral lesions=1 point, >=4 cerebral lesions=0 points, lack of extracranial metastases=1 point, and presence of extracranial metastases=0 points. Addition of these points for each patient resulted in 0-3 points. Three groups were built comprising 0-1, 2 and 3 points. Six-month survival rates for these groups were 0%, 50% and 100%, respectively. CONCLUSION: This new instrument guides physicians in choosing optimal irradiation programs for patients with cerebral metastases from head-and-neck cancer. PMID- 26359410 TI - Acute Necrotizing Pancreatitis Following Olanzapine Treatment and 759C/T Polymorphism of HTR2C Gene: A Case Report. AB - Acute pancreatitis can be attributed to numerous potential causes, such as alcohol abuse, chololithiasis, infection, lesions, tumors, hypercalcemia, hyperlipidemia, and medications. Among psychotropic medications, the use of some atypical antipsychotics, such as clozapine, olanzapine, quetiapine and risperidone, has been implicated in the development of acute pancreatitis, although the underlying mechanism has not been clarified. We describe the case of a young man with no other major medical problems, alcohol abuse or predisposing factors, who developed acute necrotizing pancreatitis following olanzapine administration, possibly through severe elevation of serum triglycerides. A pharmacogenomic analysis revealed the presence of the 5-hydroxytryptamine (serotonin) receptor 2C, G protein-coupled (HTR2C) -759C genotype which is related to increased risk for metabolic syndrome. PMID- 26359411 TI - Autologous Platelet Gel Improves Bone Reconstruction of Large Defects in Patients with Bone Giant Cell Tumors. AB - BACKGROUND/AIM: Giant cell tumors are mostly benign but locally aggressive tumors. The excision of bone tumors can result in large defects, therefore bone reconstruction is still one the most demanding procedures in orthopedic surgery. Our study addresses the opportunity for improving surgical outcome by employing beta-tricalcium phosphate (beta-TCP) with platelet-rich plasma (PRP) at the surgical site. PATIENTS AND METHODS: We included 16 patients with giant cell tumors. After adjuvant therapy, the cavity was reconstructed with beta-TCP, bone graft material (ActifuserR Granules Baxter) and platelet gel application. RESULTS: Our explorative analysis suggests a positive effect of PRP on surgical outcome in patients with giant cell tumors treated with curettage. CONCLUSION: Use of platelet gel as an adjuvant significantly reduces the time required for bone healing following intralesional treatment of benign giant cell tumors, and achieves good functional results without promoting local recurrence. PMID- 26359412 TI - Lower Levels of Vitamin D Among Bangladeshi Immigrants with Diabetes in Greece Compared to Indigenous Greek Patients with Diabetes. AB - AIM: Vitamin D deficiency is thought to impair insulin action and glucose metabolism; however, previous studies have not examined ethnic differences. We investigated a cohort of predominantly white Greek Caucasian and Bangladeshi immigrant patients with diabetes mellitus in order assess the association between diabetes mellitus and 25-hydroxyvitamin D [25(OH)VitD]. MATERIALS AND METHODS: A total of 165 patients from Bangladesh and 118 patients from Greece with diabetes were assessed for diabetes and 25(OH)VitD status. RESULTS: The 25(OH)VitD levels of Bangladeshi patients were significantly lower compared to Greek patients (12.42+/-5.86 ng/ml vs. 23.06+/-12.36 ng/ml, p<0.001). Only 1.2% of Bangladeshi patients vs. 24.57% of Greek patients had sufficient levels of 25(OH)VitD (>=30 ng/ml) CONCLUSION: The prevalence of vitamin D deficiency is very high amongst patients with diabetes but immigrants are at greater risk. Vitamin D supplementation could be valuable in the prevention or treatment of diabetes. PMID- 26359413 TI - Differences in Expression of DPP4 in Steatotic Rat Liver Are Not Related to Differences in the Methylation of its Gene Promoter. AB - The aim of the present study was to investigate the methylation status in the promoter region of Dipeptidyl peptidase-IV (Dpp4) gene, in livers from obese Zucker rats with different patterns of immunohistochemical positivity. Molecular analysis was carried-out on DNA obtained from livers of obese and lean Zucker rats and of control Wistar rats using the bisulfite conversion method and DNA sequencing. Our study focused on the genomic region of 1,000 bp, which includes the final part of 680 bp of the Dpp4 gene promoter and a small stretch of 320 bp at the beginning of the gene. The results indicate that the different immunohistochemical pattern of DPP4 observed in obese (fa/fa) and lean (fa/-) Zucker rats is not correlated to DNA methylation of its promoter. This is in agreement with the results of other studies carried-out on visceral and subcutaneous adipose tissue with varying levels of enzyme expression, in which differences in the methylation pattern of the Dpp4 promoter region were not observed. PMID- 26359414 TI - Specific Antibodies to Staphylococcus aureus Biofilm Are Present in Serum from Pigs with Osteomyelitis. AB - BACKGROUND: The Achilles heel in osteomyelitis is that bacteria, primarily Staphylococcus aureus, grow as a biofilm in the bone lesions. MATERIALS AND METHODS: In the present study, we explored the serum level of specific antibodies to S. aurues biofilm in porcine models of osteomyelitis. RESULTS: Significantly increased levels of antibodies towards the specific biofilm antigen SA0688 were measured in serum from pigs with S. aureus-associated acute and chronic osteomyelitis 5-7 and 10-14 days after inoculation, respectively. Simultaneously with raised antibody levels, an increase in serum interleukin 6 (IL 6) levels was also seen. CONCLUSION: The observed biofilm-specific antibody response represents a T-helper cell 17 (Th17) response and potentially a T-helper cell 1 (Th1) response. This is in agreement with previous studies in mice and rabbits speculating that S. aureus induces a Th1- and Th17-biased adaptive immune response, instead of a protective Th2 response, in order to evade the immune system, resulting in a chronic infection. PMID- 26359415 TI - No Dynamic Changes in Inflammation-related Microcirculatory Parameters in Developing Rats During Local Cortex Exposure to Microwaves. AB - The biological effects of exposing the developing brain to radiofrequency electromagnetic fields (RF) are still unclear. Our experiments investigated whether three inflammation-related, microcirculatory parameters in juvenile and young adult rats were modified during local cortex exposure to RF under non thermal conditions. The cortex tissue was locally exposed to 1457 MHz RF at an averaged specific absorption rate of 2.0 W/kg in the target area for 50 min and variations of pial venule parameter were measured directly in vivo. There was no significant difference in hemodynamics, plasma velocity or vessel diameter, between exposed and sham-exposed groups for either rat development stage. No increase related to RF exposure was found in leukocyte adhesion to endothelial cells in any microvessels observed. These findings suggest that RF is unlikely to initiate inflammatory responses, at least under these exposure conditions. PMID- 26359416 TI - Silybin-Phosphatidylcholine Complex Protects Human Gastric and Liver Cells from Oxidative Stress. AB - BACKGROUND/AIM: Silybin is the main component of silymarin with antioxidant, anti inflammatory and cytoprotective actions. Our aim was to compare the effect of silybin used as single substance, silybin-phosphatidylcholine complex (SilPho), and derivatives of silybin (MannpSil, GalpSil, GlcpSil, LactpSil) on MKN28 and HepG2 cell viability and cell death, in vitro, after induction of oxidative stress. MATERIALS AND METHODS: Oxidative stress was induced by incubating HepG2 and MKN28 cells with xanthine oxidase in the presence of its substrate xanthine. Cell viability was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazoliumbromide assay. Determination of Malondialdehyde (MDA) in MKN28 cells was performed by high-performance liquid chromatography. Quantitative analysis of apoptotic cells was carried-out using annexin. RESULTS: SilPho and new silybin glycoconjugates did not affect cell viability, while silybin induced about 50% cell death in both MKN28 and in HepG2 cells. Pre-treatment of cells with silybin and new silybin glycoconjugates (before oxidative stress induction) did not affect cell viability, while SilPho had a protective effect. Exposure of MKN28 cells to oxidative stress caused a two-fold increase in cellular MDA concentration compared to untreated cells. Moreover, pre-treatment with SilPho, but not with silybin, significantly prevented oxidative stress-induced increase in cellular Malondialdehyde. Moreover, silybin induced apoptosis potentiated by oxidative stress, while SilPho did not induce any effect. Oxidative stress caused cell death primarily by necrosis, antagonized by SilPho. CONCLUSION: The protective effect of SilPho is partially due to inhibition of radical oxidative species. PMID- 26359417 TI - Co-existence of BRAF V600E Gene Mutation in Tumor and Non-tumoral Surrounding Tissues in Colorectal Cancer. AB - BACKGROUND/AIM: The murine sarcoma viral (V-Raf) oncogene homolog B (BRAF) V600E mutation, which increases protein kinase activity in BRAF-mitogen-activated protein kinase kinase (MEK) - extracellular signal-regulated kinases (ERK) (mitogen-activated protein kinase (MAPK)) signaling, is found in 5-40% of all colorectal carcinoma cases. Proteins with this mutation are reported to be 130 fold more active, which results in induced proliferation, differentiation, cellular survival, and angiogenesis. The aim of the present study was to investigate tumor tissues, together with the surrounding non-tumoral tissues, for BRAF mutation presence, which may be an indicator for possible recurrence or prognosis as in the 'field carcinogenesis' model. MATERIALS AND METHODS: The BRAF V600E genotype of 152 colorectal adenocarcinoma paraffin-embedded specimens were determined by mutant-allele-specific amplification-polymerase chain reaction. RESULTS: According to our results, the presence of BRAF mutation increases risk of lymph node invasion by 1.55-fold [chi(2)=3.83, p=0.05, odds ratio (OR)=1.55, 95% confidence interval (CI)=1.00-2.42], histologically medium or high-grade tumor by 1.60-fold (chi(2)=4.34, p=0.030, OR=1.60, 95% CI=1.03-2.48), vascular invasion by 1.55-fold (chi(2)=3.55, p=0.05, OR=1.55, 95% CI=0.99-2.42), perineural invasion by 1.50-fold (chi(2)=3.16, p=0.07, OR=1.5, 95% CI=0.96-2.33) and the combination of these poor prognostic features by 1.54-fold (chi(2)=2.47, p=0.11, OR=1.54, 95% CI=0.93-2.53). We also found that females are more prone to having the mutation and that being female increases the risk of having this mutation by 1.54-fold (chi(2)=3.58, p=0.05, OR=1.54, 95% CI=0.97-2.44). CONCLUSION: BRAF V600E mutation in non-tumoral surrounding tissue in patients with colorectal cancer may be used as a valuable marker to foresee clinical outcome or a possible recurrence. To our knowledge, this was the first study to take into consideration the non-tumoral surrounding tissues in addition to the tumor tissue. PMID- 26359418 TI - Effects of U-74389G (21-Lazaroid) and Ascorbic Acid on Liver Recovery After Acute Ischemia and Reperfusion in Rats. AB - BACKGROUND/AIM: The free radical-scavenging effects of the lazaroid U-74389G have been shown in several experimental models to protect the liver from ischemia/reperfusion (I/R), however, the mechanism of cytoprotection is not fully understood. Similar findings were observed when ascorbic acid was administered. This study investigates the effects of infusion of lazaroid U-74389G and ascorbic acid on cytokines and liver structure in a liver I/R rat model. MATERIALS AND METHODS: Sixty male Wistars rats, weighting 220-290 g, were used in the study. Six experimental groups were formed: Group 1 (control group): ischemia for 30 min and reperfusion for 60 min; group 2 (control group): ischemia for 30 min and reperfusion for 120 min; group 3: ischemia for 30 min, intraportal injection of ascorbic acid, and reperfusion for 60 min; group 4: ischemia for 30 min, ascorbic acid administration, and reperfusion for 120 min; group 5: ischemia for 30 min, U 74389G administration, and reperfusion for 60 min; and group 6: ischemia for 30 min, U-74389G administration, and reperfusion for 120 min. Tissue and blood sampling took place upon completion of each model's reperfusion. U-74389G was administered at 10 mg/kg animal body weight and ascorbic acid at 100 mg/kg. Anesthesia was induced with ketamine and xylazine. Surgery was performed through a midline laparotomy. The portal vein and the common hepatic artery were isolated and prepared for occlusion. Blood samples and wedge liver biopsies were taken to measure levels of liver enzymes, cytokines and for microscopic analysis upon completion of reperfusion once for each model. RESULTS: Histopathological evaluation revealed a statistically significant reduction in the degree of necrosis of liver tissue in the treated groups compared to the control groups 1 and 2 [groups 3, 5 (p=0.010) and 4, 6 (p<0.0005)]. On the other hand, tissue malondialdehyde levels (MDA) were statistically significantly increased only between control group 2 and groups 4, 6 (p<0.0005). There was no statistically significant difference in tumor necrosis factor-alpha between groups. As for liver enzymes, only alkaline phosphatase (ALP) and gamma-glutamyl transferase (gGT) were statistically significantly reduced in treated groups 3 and 5 (ALP: p=0.027, and gGT: p=0.002) and 4 and 6 (ALP: p=0.004, and gGT: p=0.015) compared to control groups 1 and 2. CONCLUSION: Based on histological data and the reduction of some of the liver enzymes, in spite of a rise of malondialdehyde, in this rat model, administration of U-74389G in liver ischemia/reperfusion (I/R) injury has potential in attenuating liver damage. PMID- 26359419 TI - Assessment of Oxidative Stress in Septic and Obese Patients Using Markers of Oxidation-reduction Potential. AB - BACKGROUND/AIM: The novel static (sORP) and capacity (cORP) oxidation-reduction potential markers were examined for assessing oxidative stress in plasma of patients with sepsis. Moreover, the possible effect of obesity-induced oxidative stress on patients with sepsis was investigated. MATERIALS AND METHODS: sORP and cORP markers, as well as the conventional oxidative stress biomarkers total antioxidant capacity (TAC), thiobarbituric acid-reactive substances (TBARS) and protein carbonyls (CARB), were assessed in plasma. RESULTS: sORP marker was increased significantly in the sepsis group, while cORP was significantly lower compared to the control group, indicating oxidative stress. Furthermore, in patients with sepsis, TAC was significantly lower compared to control group. However, obesity had no effect on sORP, cORP and TAC in patients with sepsis, although it increased levels of CARB and TBARS. CONCLUSION: The present results suggest, for the first time, that ORP markers could be used for assessing oxidative stress in patients with sepsis. PMID- 26359420 TI - Analysis of CASP8 D302H Gene Variants in Patients with Primary Brain Tumors. AB - BACKGROUND: Alteration in cell-cycle control and apoptosis pathways play important roles in tumorigenesis. Caspase-8 (CASP8) is a member of the cysteine protease family, that is implicated in apoptosis regulation. The present study was designed to investigate the possible role of CASP8 D302H gene polymorphism in the tumor development. MATERIALS AND METHODS: A total of 91 patients with brain tumors (including 39 meningioma and 52 glioma cases) and 114 healthy controls were included in the study. We investigated CASP8 D302H polymorphism by using polymorphism chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: The CASP8 D302H polymorphism genotypic frequencies were not statistically significantly different between meningioma cases and controls, with frequencies of GG, GC and CC genotypes of 71.2%, 19,2% and 9.6%; and 57.9%, 36.8% and 5.3%, respectively. The GG/CC genotypic frequencies were significantly increased in patients with glioma patients compared to controls (p=0.023) (chi(2)=5.149, odds ratio [OR]=1.27, 95% confidence interval [CI]=1.054-1.551). According to tumor characteristics, there were no statistically significant differences within the groups with astrocytic, oligoastrocytic tumors and oligodentriogliomas. CONCLUSION: D302H polymorphism of CASP8 gene may be associated with increased risk of glioma but larger study groups in different ethnic populations are needed to better elucidate the role of CASP8 gene polymorphism in the pathogenesis of primary brain tumors. PMID- 26359421 TI - Melatonin: Free Radicals and Metabolites Resulting by Emission and Consumption of Solvated Electrons (eaq-): Reaction Mechanisms. AB - BACKGROUND/AIM: Melatonin not only regulates circadian rhythm, but also induces apoptosis in tumor cells. Hence, elucidation of the basic reaction mechanisms of melatonin and its metabolites is a matter of interest. MATERIAL AND METHODS: Melatonin dissolved in a mixture of water/ethanol=40/60 form associates (unstable complexes). For simulation of biological processes, melatonin was excited by UV light into the singlet state. RESULTS: By using monochromatic UV light (lambda=254 nm) melatonin ejects solvated electrons (eaq (-)), a part of which is scavenged by melatonin in ground state contained in the associates. Consequently, with increase of melatonin concentration a decrease of the determined quantum yield of emitted eaq (-), Q(eaq (-)), is obtained. The complex molecular structure of melatonin contains functional groups which can emit eaq (-), as well such consuming eaq (-). As a succession of these processes various types of metabolites are generated, as well as degradation products, with lower molecular weight, are formed. CONCLUSION: Not melatonin per se, but the ejected eaq (-) and thereby resulting various metabolites are responsible for different biological properties of melatonin. PMID- 26359422 TI - Inhibition of Cell Growth of the Prostate Cancer Cell Model LNCaP by Cold Atmospheric Plasma. AB - Backround/Aim: Physical plasmas are ionized gases containing several biologically reactive factors that yet exert their anti-microbial and anti-proliferative effects in fields of surface sterilisation, de-contamination and wound healing. MATERIALS AND METHODS: Cold atmospheric plasma (CAP) was generated via the atmospheric pressure plasma jet kINPen09. Apoptotic effects of CAP treatment on the human epithelial prostate cancer cell line LNCaP as a cell culture model for malignant tumor tissue was analyzed by cell counting, western blot and quantitative reverse transcription-polymerase chain reaction analysis. RESULTS: LNCaP cells exhibited significantly reduced cell growth following CAP treatment. We show that most probably the induction of apoptosis is the terminus of CAP treatment illustrated by the pro-apoptotic modulation of p53, p21, caspase-3, Bax, and survivin, as well as morphological changes of cell architecture. CONCLUSION: Our in vitro study offers first indicatory results for molecular response mechanisms after CAP treatment in a suitable LNCaP cell model. PMID- 26359423 TI - Errata. PMID- 26359424 TI - No evidence of sexual niche partitioning in a dioecious moss with rare sexual reproduction. AB - BACKGROUND AND AIMS: Roughly half of the species of bryophytes have separate sexes (dioecious) and half are hermaphroditic (monoecious). This variation has major consequences for the ecology and evolution of the different species. In some sexually reproducing dioecious bryophytes, sex ratio has been shown to vary with environmental conditions. This study focuses on the dioecious wetland moss Drepanocladus trifarius, which rarely produces sexual branches or sporophytes and lacks apparent secondary sex characteristics, and examines whether genetic sexes exhibit different habitat preferences, i.e. whether sexual niche partitioning occurs. METHODS: A total of 277 shoots of D. trifarius were randomly sampled at 214 locations and 12 environmental factors were quantified at each site. Sex was assigned to the individual shoots collected in the natural environments, regardless of their reproductive status, using a specifically designed molecular marker associated with female sex. KEY RESULTS: Male and female shoots did not differ in shoot biomass, the sexes were randomly distributed with respect to each other, and environmental conditions at male and female sampling locations did not differ. Collectively, this demonstrates a lack of sexual niche segregation. Adult genetic sex ratio was female-biased, with 2.8 females for every male individual. CONCLUSIONS: The results show that although the sexes of D. trifarius did not differ with regard to annual growth, spatial distribution or habitat requirements, the genetic sex ratio was nevertheless significantly female-biased. This supports the notion that factors other than sex-related differences in reproductive costs and sexual dimorphism can also drive the evolution of biased sex ratios in plants. PMID- 26359425 TI - Genetic assimilation: a review of its potential proximate causes and evolutionary consequences. AB - BACKGROUND: Most, if not all, organisms possess the ability to alter their phenotype in direct response to changes in their environment, a phenomenon known as phenotypic plasticity. Selection can break this environmental sensitivity, however, and cause a formerly environmentally induced trait to evolve to become fixed through a process called genetic assimilation. Essentially, genetic assimilation can be viewed as the evolution of environmental robustness in what was formerly an environmentally sensitive trait. Because genetic assimilation has long been suggested to play a key role in the origins of phenotypic novelty and possibly even new species, identifying and characterizing the proximate mechanisms that underlie genetic assimilation may advance our basic understanding of how novel traits and species evolve. SCOPE: This review begins by discussing how the evolution of phenotypic plasticity, followed by genetic assimilation, might promote the origins of new traits and possibly fuel speciation and adaptive radiation. The evidence implicating genetic assimilation in evolutionary innovation and diversification is then briefly considered. Next, the potential causes of phenotypic plasticity generally and genetic assimilation specifically are examined at the genetic, molecular and physiological levels and approaches that can improve our understanding of these mechanisms are described. The review concludes by outlining major challenges for future work. CONCLUSIONS: Identifying and characterizing the proximate mechanisms involved in phenotypic plasticity and genetic assimilation promises to help advance our basic understanding of evolutionary innovation and diversification. PMID- 26359426 TI - Adult Lung Spheroid Cells Contain Progenitor Cells and Mediate Regeneration in Rodents With Bleomycin-Induced Pulmonary Fibrosis. AB - Lung diseases are devastating conditions and ranked as one of the top five causes of mortality worldwide according to the World Health Organization. Stem cell therapy is a promising strategy for lung regeneration. Previous animal and clinical studies have focused on the use of mesenchymal stem cells (from other parts of the body) for lung regenerative therapies. We report a rapid and robust method to generate therapeutic resident lung progenitors from adult lung tissues. Outgrowth cells from healthy lung tissue explants are self-aggregated into three dimensional lung spheroids in a suspension culture. Without antigenic sorting, the lung spheroids recapitulate the stem cell niche and contain a natural mixture of lung stem cells and supporting cells. In vitro, lung spheroid cells can be expanded to a large quantity and can form alveoli-like structures and acquire mature lung epithelial phenotypes. In severe combined immunodeficiency mice with bleomycin-induced pulmonary fibrosis, intravenous injection of human lung spheroid cells inhibited apoptosis, fibrosis, and infiltration but promoted angiogenesis. In a syngeneic rat model of pulmonary fibrosis, lung spheroid cells outperformed adipose-derived mesenchymal stem cells in reducing fibrotic thickening and infiltration. Previously, lung spheroid cells (the spheroid model) had only been used to study lung cancer cells. Our data suggest that lung spheroids and lung spheroid cells from healthy lung tissues are excellent sources of regenerative lung cells for therapeutic lung regeneration. SIGNIFICANCE: The results from the present study will lead to future human clinical trials using lung stem cell therapies to treat various incurable lung diseases, including pulmonary fibrosis. The data presented here also provide fundamental knowledge regarding how injected stem cells mediate lung repair in pulmonary fibrosis. PMID- 26359427 TI - "First, I... then, we...": exploring the sequence of sexual acts and safety strategies reported during a sexual encounter using a modified timeline followback method. AB - OBJECTIVES: Assessments of sexual safety often rely on questions about the occurrence of condom use within a designated timeline, assuming that penile vaginal intercourse (PVI) occurred once at the conclusion of the event. An investigation of all sexual acts and safety strategies that occur during a single event may present a more nuanced picture of sexual risk. METHODS: Behaviourally, bisexual women (N=45) were recruited due to the potential diversity of their sexual behaviour and safety strategies. A modified timeline follow-back method, the SEQUENCE Calendar, was designed to capture information about the participants' most recent sexual event with a male partner, including the order of each sexual act during the sexual event. Interviews took between 1 and 3 h. These acts were compiled into narratives and the behavioural sequences were reviewed and coded. RESULTS: Participants reported an average of 7.9 (SD=4.3) sexual acts. Over a third (35.9%, N=14) of the participants who reported PVI indicated engaging in genital contact after PVI and over 15% (N=6) of these participants reporting PVI at two different time points, separated by sexual behaviour. Additional potential for infection outside of condom use and PVI was also identified. CONCLUSIONS: Sexual interactions are comprised of multiple acts that occur in a variety of permutations. Understanding the complexity of people's sexual encounters has potential to inform the ways we measure condom use and consider sexual safety. PMID- 26359428 TI - More than one way to shrink. PMID- 26359429 TI - "Blood feuds". PMID- 26359430 TI - GVHD and miR: good things in small packages. PMID- 26359431 TI - Directing CLL-cell traffic. PMID- 26359432 TI - Exploiting AML vulnerability: glutamine dependency. PMID- 26359433 TI - New players in Trousseau syndrome. PMID- 26359434 TI - Dexamethasone, rituximab, and cyclophosphamide as primary treatment of Waldenstrom macroglobulinemia: final analysis of a phase 2 study. PMID- 26359435 TI - Nicholas Mrosovsky. PMID- 26359436 TI - Corrigendum. AB - Guedes RS, Piovesan C, Ardenghi TM, Emmanuelli B, Braga MM, Ekstrand KR, Mendes FM. 2014. Validation of visual caries activity assessment: a 2-year cohort study. J Dent Res. 93(7 suppl):101S-107S. (Original DOI: 10.1177/0022034514531017)The authors regret that they did not adequately provide credit to the original source of the scoring system used as a part of the manuscript, highlighted in Table 1. The following reference from Nyvad et al. should have been included:Nyvad B, Machiulskiene V, Baelum V. 1999. Reliability of a new caries diagnostic system differentiating between active and inactive caries lesions. Caries Res. 33(4):252 260. PMID- 26359437 TI - Coagulation factor XIIIa is inactivated by plasmin. AB - Coagulation factor XIIIa (FXIIIa) is a transglutaminase that covalently cross links fibrin and other proteins to fibrin to stabilize blood clots and reduce blood loss. A clear mechanism to describe the physiological inactivation of FXIIIa has been elusive. Here, we show that plasmin can cleave FXIIIa in purified systems and in blood. Whereas zymogen FXIII was not readily cleaved by plasmin, FXIIIa was rapidly cleaved and inactivated by plasmin in solution (catalytic efficiency = 8.3 * 10(3) M(-1)s(-1)). The primary cleavage site identified by mass spectrometry was between K468 and Q469. Both plasma- and platelet-derived FXIIIa were susceptible to plasmin-mediated degradation. Inactivation of FXIIIa occurred during clot lysis and was enhanced both in plasma deficient in fibrinogen and in plasma treated with therapeutic levels of tissue plasminogen activator. These results indicate that FXIIIa activity can be modulated by fibrinolytic enzymes, and suggest that changes in fibrinolytic activity may influence cross-linking of blood proteins. PMID- 26359438 TI - Impact of Fenestrated Endovascular Abdominal Aortic Aneurysm Repair on Renal Function. AB - PURPOSE: To investigate the impact of fenestrated endovascular aneurysm repair (fEVAR) on renal function perioperatively and at midterm. METHODS: A case controlled study was performed involving 58 patients (mean age 75+/-7 years; 51 men) who underwent elective fEVAR for a juxtarenal or short-necked abdominal aortic aneurysm (AAA) matched on age, sex, smoking, diabetes, and baseline estimated glomerular filtration rate (eGFR) with a contemporaneous group undergoing open aneurysm repair (OAR) for the same indications. Perioperative incidence of acute kidney injury (AKI) and levels of eGFR at 30 days and 1 year were compared. A systematic literature review was performed to identify studies that had used eGFR as renal outcome after fEVAR; the pooled data were meta analyzed using an eGFR drop >30% at 1 month and the latest follow-up as endpoints. Results are reported as the pooled proportion and 95% confidence interval (CI). RESULTS: The incidence of AKI after fEVAR was 28% compared to 10% after OAR (p=0.03). Following fEVAR, the mean eGFR dropped from 78+/-8 to 74+/-9 mL/min/1.73 m(2) at 30 days compared to a change from 79+/-8 to 80+/-16 mL/min/1.73 m(2) after OAR (p<0.01). However, the absolute drop in eGFR between fEVAR and OAR at 1 year was similar (7 mL/min/1.73 m(2); p=0.53); 7% of the fEVAR patients had an eGFR drop >30% at that point compared with none for OAR (p=0.12). The systematic literature review identified eGFR outcomes for 193 fEVAR patients. Combining these patients with the 58 from our cohort study, the pooled proportions of eGFR drop >30% were 20% (95% CI 9% to 39%) at 30 days and 8% (95% CI 0.5% to 13%) at the end of follow-up. CONCLUSION: fEVAR has a significant perioperative impact on renal function, but 1-year results are similar to OAR. fEVAR patients may benefit from targeted AKI prevention strategies that need to be assessed in relevant studies. PMID- 26359439 TI - Peptides that form amyloid plaques in Alzheimer's may be transmissible, study finds. PMID- 26359440 TI - NICE approves first drug under the early access to medicines scheme. PMID- 26359441 TI - A cross-sectional assessment of the long term effects of brief strategic family therapy for adolescent substance use. AB - BACKGROUND: Young adult drug use and law-breaking behaviors often have roots in adolescence. These behaviors are predicted by early drug use, parental substance use disorders, and disrupted and conflict-ridden family environments. AIM: To examine long-term outcomes of Brief Strategic Family Therapy (BSFT) compared to treatment as usual (TAU) in the rates of drug use, number of arrests and externalizing behaviors in young adults who were randomized into treatment conditions as adolescents. DESIGN: 261 of 480 adolescents who had been randomized to BSFT or TAU in the BSFT effectiveness study were assessed at a single time, 3 7 years post randomization. METHODS: Assessments of drug use, externalizing behaviors, arrests and incarcerations were conducted using Timeline Follow Back, Adult Self Report, and self-report, respectively. Drug use, arrests and incarcerations were examined using negative binomial models and externalizing behaviors were examined using linear regression. RESULTS: When compared with TAU, BSFT youth reported lower incidence of lifetime (IRR = 0.68, 95%CI [0.57, 0.81]) and past year (IRR = 0.54, 95%CI [0.40, 0.71]) arrests; lower rates of lifetime (IRR = 0.63, 95%CI [0.49, 0.81]) and past year (IRR = 0.70, 95%CI [0.53, 0.92]) incarcerations; and lower scores on externalizing behaviors at follow-up (B = 0.42, SE = .15, p = .005). There were no differences in drug use. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: BSFT may have long term effects in reducing the number of arrests, incarcerations and externalizing problems. These effects could be explained by the improvements in family functioning that occurred during the effectiveness study. This study contributes to the literature by reporting on the long term outcomes of family therapy for adolescent drug abuse. PMID- 26359442 TI - The refugee crisis: what care is needed and how can doctors help? PMID- 26359443 TI - Anxiety, mood disorders and injection risk behaviors among cocaine users: Results from the COSMO study. AB - BACKGROUND AND OBJECTIVES: Despite being common among cocaine users, mental health problems and their relationship with HIV and hepatitis C high risk injection behaviors are poorly documented. This study was undertaken to examine the relationships between mood and anxiety disorders and the sharing of drug injection equipment among cocaine users who inject drugs. METHODS: The sample was drawn from a prospective cohort study and comprised of 387 participants. The outcome of interest was "sharing injection material" in the past 3 months. The presence of mood and anxiety disorders during the past year was assessed using the CIDI questionnaire. Statistical analyses were conducted on baseline data using logistic regression. RESULTS: Most participants were male (84.5%) and were aged 25 or over (92.2%); 43.0% qualified for an anxiety disorder diagnosis and 29.3% for a mood disorder diagnosis. Participants with anxiety disorders were more likely to share needles (Adjusted Odds Ratio [AOR]: 2.13, 95%CI: 1.15-3.96) and other injection material (AOR: 1.81, 95%CI: 1.12-2.92). No significant association was found between mood disorders and sharing behaviors. DISCUSSION AND CONCLUSIONS: Primary anxiety disorders but not mood disorders increases injection risk behaviors among cocaine users. These results bring to light another negative outcome of mental health comorbidity in this vulnerable population. SCIENTIFIC SIGNIFICANCE: This study underlines the need to fine-tune therapeutic approaches targeting specific mental health problems in individuals with cocaine use disorders. Longitudinal studies that assess impulsivity and other correlates of psychiatric disorders are needed to examine underlying mechanisms of high risk injection behaviors in comorbid populations. PMID- 26359444 TI - Increased risk for substance use and health-related problems among homeless veterans. AB - BACKGROUND AND OBJECTIVES: The first aim of this study was to compare self reported causes of homelessness between veterans and nonveterans. A second aim examined whether homeless male veterans were more likely than homeless male nonveterans to experience current problems with addictions, mental health, and physical health. Additionally, a third aim was to compare frequency of emergency room visits and treatment needs between the two groups. METHODS: Secondary data analyses compared male homeless veterans and nonveterans (N = 353) enrolled in the Alachua County Point in Time study in central Florida. Participants completed a questionnaire on demographics and health variables. Additional questions included recent emergency room visits and medical or other needs not being met. RESULTS: Veterans reported higher rates of substance use and mental health problems as a primary cause of homelessness when compared to nonveterans. Homeless veterans were more likely than nonveterans to report current problems with addictions (OR = 6.29, 95% CI: 3.43-11.53, p < .001), mental health problems (OR = 4.12, 95% CI: 2.28-7.42, p < .001), and physical problems (OR = 1.83, 95% CI: 1.08-3.67, p < .01). Finally, over half of homeless veterans (53.1%) reported an ER visit in the past year compared to only 40.9% of nonveterans (OR = 1.73, 95% CI: 1.07-2.80, p < .05). CONCLUSION AND SCIENTIFIC SIGNIFICANCE: Veterans may be more likely to become homeless due to addiction and mental health and over half of homeless veterans are presenting to hospital emergency rooms. Given the greater utilization among homeless veterans, emergency rooms may serve as a prime opportunity to provide brief treatment and referrals for needed services. PMID- 26359445 TI - New cholesterol drugs are overpriced, independent analysis finds. PMID- 26359446 TI - The missing piece: cancer prevention within psycho-oncology - a commentary. AB - In this commentary, we review the place of prevention within the field of Psycho Oncology. The thrust of Psycho-Oncology's clinical and research efforts have historically focused on behavioral and social factors implicated in the cancer patients' experience from detection and diagnosis, to treatment, survivorship and end of life along the cancer trajectory. This conceptualization has raised the standards for research, leading to a better understanding of the patient experience and the delivery of highly effective interventions to improve quality of life. Emerging data on the role of potential prevention behaviors (e.g., diet and exercise, smoking cessation, screening, etc.) suggests that Psycho-Oncology has a significant role to play in understanding and intervening on a population level to reduce cancer incidence. We present and describe an expanded model of research in Psycho-Oncology which incorporates psychosocial variables in prevention research to complement Holland et al.'s (1998, 2010) original model. The implications of this model are discussed in relation to research, clinical work and training within the discipline of Psycho-Oncology. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26359447 TI - Ohio runs out of execution drugs as manufacturers' embargo bites across US. PMID- 26359448 TI - Pre-exposure prophylaxis is effective at preventing HIV in high risk gay men, study shows. PMID- 26359450 TI - Decreased expression of neuropilin-1 as a novel key factor contributing to peripheral microvasculopathy and defective angiogenesis in systemic sclerosis. AB - OBJECTIVES: In systemic sclerosis (SSc), vascular involvement is characterised by vascular endothelial growth factor (VEGF)-A/VEGF receptor (VEGFR) system disturbances. Neuropilin-1 (NRP1), a receptor for both class-3 semaphorins (Sema3s) and VEGF-A, is required for optimal VEGF-A/VEGFR-2 signalling. Here, we investigated the possible involvement of Sema3A/NRP1 axis in SSc. METHODS: Circulating Sema3A and soluble NRP1 (sNRP1) were measured in patients with SSc and controls. NRP1 and Sema3A expression in skin biopsies was evaluated by immunofluorescence and western blotting. NRP1 expression was assessed in SSc and healthy dermal microvascular endothelial cells (SSc-MVECs and H-MVECs), and in SSc and control endothelial progenitor cell (EPC)-derived endothelial cells (ECs). The possible impact of transcription factor Friend leukaemia integration 1 (Fli1) deficiency on endothelial NRP1 expression was investigated by gene silencing. The binding of Fli1 to NRP1 gene promoter was evaluated using chromatin immunoprecipitation. Capillary morphogenesis was performed on Matrigel. RESULTS: Decreased sNRP1 levels in SSc were associated with active and late nailfold videocapillaroscopy patterns and digital ulcers. No difference in Sema3A was found between patients and controls. NRP1 was significantly decreased in SSc MVECs both ex vivo and in vitro. NRP1 and Fli1 significantly decreased in H-MVECs challenged with SSc sera, while they were not different in SSc and control EPC derived ECs. Fli1 occupied the NRP1 gene promoter and Fli1 gene silencing reduced NRP1 expression in H-MVECs. NRP1 gene silencing in H-MVECs resulted in a significantly impaired angiogenic capacity comparable to that of cells treated with SSc sera. CONCLUSION: In SSc, NRP1 deficiency may be an additional factor in the perturbed VEGF-A/VEGFR-2 system contributing to peripheral microvasculopathy and defective angiogenesis. PMID- 26359449 TI - Impact of baseline anti-cyclic citrullinated peptide-2 antibody concentration on efficacy outcomes following treatment with subcutaneous abatacept or adalimumab: 2-year results from the AMPLE trial. AB - OBJECTIVES: To examine whether baseline anti-cyclic citrullinated peptide-2 (CCP2) antibody status and concentration correlated with clinical outcomes in patients treated with abatacept or adalimumab on background methotrexate (MTX) in the 2-year AMPLE (Abatacept versus adaliMumab comParison in bioLogic-naivE rheumatoid arthritis subjects with background MTX) study. METHODS: In this exploratory analysis, anti-CCP2 antibody concentration was measured at baseline, and antibody-positive patients were divided into equal quartiles, Q1-Q4, representing increasing antibody concentrations. Clinical outcomes analysed by baseline anti-CCP2 status and quartile included change from baseline in disease activity and disability and remission rates. RESULTS: Baseline characteristics were generally comparable across quartiles and treatment groups. In both treatment groups, anti-CCP2 antibody-negative patients responded less well than antibody-positive patients. At year 2, improvements in disease activity and disability and remission rates were similar across Q1-Q3, but were numerically higher in Q4 in the abatacept group; in contrast, treatment effects were similar across all quartiles in the adalimumab group. CONCLUSIONS: In AMPLE, baseline anti-CCP2 positivity was associated with a better response for abatacept and adalimumab. Patients with the highest baseline anti-CCP2 antibody concentrations had better clinical response with abatacept than patients with lower concentrations, an association that was not observed with adalimumab. TRIAL REGISTRATION NUMBER: NCT00929864. PMID- 26359451 TI - Cancer stem cell marker phenotypes are reversible and functionally homogeneous in a preclinical model of pancreatic cancer. AB - Survival rates associated with pancreatic cancer remain dismal despite advancements in detection and experimental treatment strategies. Genetically engineered mouse models of pancreatic tumorigenesis have gained considerable attention based on their ability to recapitulate key clinical features of human disease including chemotherapeutic resistance and fibrosis. However, it is unclear if transgenic systems exemplified by the Kras(G12D)/Trp53(R172H)/Pdx-1 Cre (KPC) mouse model recapitulate the functional heterogeneity of human pancreatic tumors harboring distinct cells with tumorigenic properties. To facilitate tracking of heterogeneous tumor cell populations, we incorporated a luciferase-based tag into the genetic background of the KPC mouse model. We isolated pancreatic cancer cells from multiple independent tumor lines and found that roughly 1 out of 87 cells exhibited tumorigenic capability. Notably, this frequency is significantly higher than reported for human pancreatic adenocarcinomas. Cancer stem cell (CSC) markers, including CD133, CD24, Sca-1, and functional Aldefluor activity, were unable to discriminate tumorigenic from nontumorigenic cells in syngeneic transplants. Furthermore, three-dimensional spheroid cultures originating from KPC tumors did not enrich for cells with stem like characteristics and were not significantly more tumorigenic than cells cultured as monolayers. Additionally, we did not observe significant differences in response to gemcitabine or salinomycin in several isolated subpopulations. Taken together, these studies show that the hierarchical organization of CSCs in human disease is not recapitulated in a commonly used mouse model of pancreatic cancer and therefore provide a new view of the phenotypic and functional heterogeneity of tumor cells. PMID- 26359452 TI - Kinome RNAi Screens Reveal Synergistic Targeting of MTOR and FGFR1 Pathways for Treatment of Lung Cancer and HNSCC. AB - The FGFR1 is a therapeutic target under investigation in multiple solid tumors and clinical trials of selective tyrosine kinase inhibitors (TKI) are underway. Treatment with a single TKI represents a logical step toward personalized cancer therapy, but intrinsic and acquired resistance mechanisms limit their long-term benefit. In this study, we deployed RNAi-based functional genomic screens to identify protein kinases controlling the intrinsic sensitivity of FGFR1-dependent lung cancer and head and neck squamous cell cancer (HNSCC) cells to ponatinib, a multikinase FGFR-active inhibitor. We identified and validated a synthetic lethal interaction between MTOR and ponatinib in non-small cell lung carcinoma cells. In addition, treatment with MTOR-targeting shRNAs and pharmacologic inhibitors revealed that MTOR is an essential protein kinase in other FGFR1-expressing cancer cells. The combination of FGFR inhibitors and MTOR or AKT inhibitors resulted in synergistic growth suppression in vitro. Notably, tumor xenografts generated from FGFR1-dependent lung cancer cells exhibited only modest sensitivity to monotherapy with the FGFR-specific TKI, AZD4547, but when combined with the MTOR inhibitor, AZD2014, significantly attenuated tumor growth and prolonged survival. Our findings support the existence of a signaling network wherein FGFR1-driven ERK and activated MTOR/AKT represent distinct arms required to induce full transformation. Furthermore, they suggest that clinical efficacy of treatments for FGFR1-driven lung cancers and HNSCC may be achieved by combining MTOR inhibitors and FGFR-specific TKIs. PMID- 26359454 TI - Cytosolic TMEM88 promotes invasion and metastasis in lung cancer cells by binding DVLS. AB - Transmembrane protein 88 (TMEM88) is a transmembrane protein that plays a crucial role in regulating human stem cell differentiation and embryonic development. However, its expression and clinicopathologic significance in human neoplasms is unclear. In this study, the expression and subcellular localizations of TMEM88 were assessed in 214 cases of non-small cell lung cancer (NSCLC). Notably, TMEM88 was highly expressed in the cytosol of ~60% NSCLC specimens examined. Higher expression of cytosolic TMEM88 in NSCLC correlated significantly with poor differentiation, high TNM stage, lymph node metastasis, and inferior survival. In NSCLC cells displaying membrane-localized TMEM88, we observed an inhibition of canonical Wnt signaling due to interactions of TMEM88 with the Wnt pathway factor Dishevelled (DVLS). In contrast, NSCLC cells with cytosol-localized TMEM88 lacked effects on Wnt signaling. Cytosolic interactions of TMEM88 and DVLS increased the expression of phosphorylated, active forms of p38, GSK3beta (Thr390), and Snail, thereby reducing the expression of the tight junction-associated proteins ZO-1 and occludin, effects associated with enhanced invasive and metastatic cell characters. Importantly, attenuating the expression of cytosolic TMEM88 reduced metastatic prowess in xenograft models. Overall, our findings show how mislocalization of TMEM88 to the cytosol in NSCLC cells ablates its Wnt pathway regulatory properties, thereby promoting invasion and metastasis by activating the p38-GSK3beta-Snail signaling pathway. PMID- 26359453 TI - A systematic analysis reveals heterogeneous changes in the endocytic activities of cancer cells. AB - Metastasis is a multistep process requiring cancer cell signaling, invasion, migration, survival, and proliferation. These processes require dynamic modulation of cell surface proteins by endocytosis. Given this functional connection, it has been suggested that endocytosis is dysregulated in cancer. To test this, we developed In-Cell ELISA assays to measure three different endocytic pathways: clathrin-mediated endocytosis, caveolae-mediated endocytosis, and clathrin-independent endocytosis and compared these activities using two different syngeneic models for normal and oncogene-transformed human lung epithelial cells. We found that all endocytic activities were reduced in the transformed versus normal counterparts. However, when we screened 29 independently isolated non-small cell lung cancer (NSCLC) cell lines to determine whether these changes were systematic, we observed significant heterogeneity. Nonetheless, using hierarchical clustering based on their combined endocytic properties, we identified two phenotypically distinct clusters of NSCLCs. One co clustered with mutations in KRAS, a mesenchymal phenotype, increased invasion through collagen and decreased growth in soft agar, whereas the second was enriched in cells with an epithelial phenotype. Interestingly, the two clusters also differed significantly in clathrin-independent internalization and surface expression of CD44 and CD59. Taken together, our results suggest that endocytotic alterations in cancer cells that affect cell surface expression of critical molecules have a significant influence on cancer-relevant phenotypes, with potential implications for interventions to control cancer by modulating endocytic dynamics. PMID- 26359455 TI - Combining miR-10b-Targeted Nanotherapy with Low-Dose Doxorubicin Elicits Durable Regressions of Metastatic Breast Cancer. AB - The therapeutic promise of microRNA (miRNA) in cancer has yet to be realized. In this study, we identified and therapeutically exploited a new role for miR-10b at the metastatic site, which links its overexpression to tumor cell viability and proliferation. In the protocol developed, we combined a miR-10b-inhibitory nanodrug with low-dose anthracycline to achieve complete durable regressions of metastatic disease in a murine model of metastatic breast cancer. Mechanistic investigations suggested a potent antiproliferative, proapoptotic effect of the nanodrug in the metastatic cells, potentiated by a cell-cycle arrest produced by administration of the low-dose anthracycline. miR-10b was overexpressed specifically in cells with high metastatic potential, suggesting a role for this miRNA as a metastasis-specific therapeutic target. Taken together, our results implied the existence of pathways that regulate the viability and proliferation of tumor cells only after they have acquired the ability to grow at distant metastatic sites. As illustrated by miR-10b targeting, such metastasis-dependent apoptotic pathways would offer attractive targets for further therapeutic exploration. PMID- 26359456 TI - Implication of the Autologous Immune System in BCR-ABL Transcript Variations in Chronic Myelogenous Leukemia Patients Treated with Imatinib. AB - Imatinib and other tyrosine kinase inhibitors (TKI) have improved treatment of chronic myelogenous leukemia (CML); however, most patients are not cured. Deeper mechanistic understanding may improve TKI combination therapies to better control the residual leukemic cell population. In analyzing our patients' data, we found that many patients who otherwise responded well to imatinib therapy still showed variations in their BCR-ABL transcripts. To investigate this phenomenon, we applied a mathematical model that integrates CML and an autologous immune response to the patients' data. We define an immune window or a range of leukemic loads for which the autologous immune system induces an improved response. Our modeling results suggest that, at diagnosis, a patient's leukemic load is able to partially or fully suppress the autologous immune response developed in a majority of patients, toward the CML clone(s). Imatinib therapy drives the leukemic population into the "immune window," allowing the patient's autologous immune cells to expand and eventually mount an efficient recognition of the residual leukemic burden. This response drives the leukemic load below this immune window, allowing the leukemic population to partially recover until another weaker immune response is initiated. Thus, the autologous immune response may explain the oscillations in BCR-ABL transcripts regularly observed in patients on imatinib. PMID- 26359457 TI - Mitochondrial Superoxide Dismutase Has a Protumorigenic Role in Ovarian Clear Cell Carcinoma. AB - Epithelial ovarian cancer (EOC) is the fourth leading cause of death due to cancer in women and comprises distinct histologic subtypes, which vary widely in their genetic profiles and tissues of origin. It is therefore imperative to understand the etiology of these distinct diseases. Ovarian clear cell carcinoma (OCCC), a very aggressive subtype, comprises >10% of EOCs. In the present study, we show that mitochondrial superoxide dismutase (Sod2) is highly expressed in OCCC compared with other EOC subtypes. Sod2 is an antioxidant enzyme that converts highly reactive superoxide (O2 (*-)) to hydrogen peroxide (H2O2) and oxygen (O2), and our data demonstrate that Sod2 is protumorigenic and prometastatic in OCCC. Inhibiting Sod2 expression reduces OCCC ES-2 cell tumor growth and metastasis in a chorioallantoic membrane (CAM) model. Similarly, cell proliferation, migration, spheroid attachment and outgrowth on collagen, and Akt phosphorylation are significantly decreased with reduced expression of Sod2. Mechanistically, we show that Sod2 has a dual function in supporting OCCC tumorigenicity and metastatic spread. First, Sod2 maintains highly functional mitochondria, by scavenging O2 (*-), to support the high metabolic activity of OCCC. Second, Sod2 alters the steady-state ROS balance to drive H2O2-mediated migration. While this higher steady-state H2O2 drives prometastatic behavior, it also presents a doubled-edged sword for OCCC, as it pushed the intracellular H2O2 threshold to enable more rapid killing by exogenous sources of H2O2. Understanding the complex interaction of antioxidants and ROS may provide novel therapeutic strategies to pursue for the treatment of this histologic EOC subtype. PMID- 26359458 TI - Targeting the MDM2/MDM4 interaction interface as a promising approach for p53 reactivation therapy. AB - Restoration of wild-type p53 tumor suppressor function has emerged as an attractive anticancer strategy. Therapeutics targeting the two p53-negative regulators, MDM2 and MDM4, have been developed, but most agents selectively target the ability of only one of these molecules to interact with p53, leaving the other free to operate. Therefore, we developed a method that targets the activity of MDM2 and MDM4 simultaneously based on recent studies indicating that formation of MDM2/MDM4 heterodimer complexes are required for efficient inactivation of p53 function. Using computational and mutagenesis analyses of the heterodimer binding interface, we identified a peptide that mimics the MDM4 C terminus, competes with endogenous MDM4 for MDM2 binding, and activates p53 function. This peptide induces p53-dependent apoptosis in vitro and reduces tumor growth in vivo. Interestingly, interfering with the MDM2/MDM4 heterodimer specifically activates a p53-dependent oxidative stress response. Consistently, distinct subcellular pools of MDM2/MDM4 complexes were differentially sensitive to the peptide; nuclear MDM2/MDM4 complexes were particularly highly susceptible to the peptide-displacement activity. Taken together, these data identify the MDM2/MDM4 interaction interface as a valuable molecular target for therapeutic reactivation of p53 oncosuppressive function. PMID- 26359459 TI - Feed-Forward Reciprocal Activation of PAFR and STAT3 Regulates Epithelial Mesenchymal Transition in Non-Small Cell Lung Cancer. AB - Platelet-activating factor receptor (PAFR), a G-protein-coupled receptor, has been implicated in tumorigenesis, but its contributions to metastatic progression have not been investigated. Here, we show that PAFR is overexpressed in non-small cell lung cancer (NSCLC) as well as in breast, colorectal, and gastric carcinomas. Expression of PAFR correlates closely with clinical stages, survival time, and distant metastasis. In human NSCLC cells, activation of the PAF/PAFR signaling axis accentuated malignant character, including by stimulating epithelial-mesenchymal transition (EMT). In contrast, silencing PAFR in aggressive NSCLC cells inhibited these effects. Mechanistic investigations showed that PAFR stimulated EMT by activating STAT3 via upregulation of G-protein dependent SRC or JAK2 kinase activity. Notably, STAT3 transcriptionally elevated PAFR expression. Thus, activation of PAFR in NSCLC cells initiated a forward feedback loop responsible for mediating the aggressive malignant character of NSCLC cells in vitro and in vivo. Reinforcing this reciprocal activation loop, PAF/PAFR signaling also upregulated IL6 expression and thereby STAT3 activation. Overall, our results elucidated an important role for PAFR dysregulation in the pathogenicity of NSCLC and unraveled a forward feedback loop between PAFR and STAT3 that acts to drive the malignant progression of NSCLC. PMID- 26359461 TI - Palliative care conundrums in an Ebola treatment centre. AB - We describe the treatment course and last days of a 33-year-old man from Western Africa who died from Ebola-related complications. Specifically, the issues around declaring a patient palliative in a low resource environment while dealing with a largely unknown entity, Ebola viral disease, make this an important discussion stimulating case. The patient presented as a confirmed Ebola-positive case from a peripheral holding centre and then proceeded to deteriorate under our care. Significant neurological decline was noted and the prognosis was felt to be grim by certain providers. Other providers disagreed and a number of treatment algorithms were started and stopped during the patient's last days. He succumbed to Ebola complications after 17 days under our care. PMID- 26359462 TI - Acupuncture for episodic cluster headache: a trigeminal approach. AB - Following evidence that acupuncture is clinically feasible and cost-effective in the treatment of headache, the UK National Institute for Health and Care Excellence recommends acupuncture as prophylactic treatment for migraine and tension headache. There has thus been expectation that other forms of headache should benefit also. Unfortunately, acupuncture has not generally been successful for cluster headache. This may be due to acupuncturists approaching the problem as one of severe migraine. In fact, cluster headache is classed as a trigeminal autonomic cephalgia. In this case report, episodic cluster headache is treated in the same way as has been shown effective for trigeminal neuralgia. Acupuncture is applied to the contralateral side at points appropriate for stimulating branches of the trigeminal nerve. Thus, ST2 is used for the infraorbital nerve, BL2 and Yuyao for the supratrochlear and supraorbital nerves, and Taiyang for the temporal branch of the zygomatic nerve. PMID- 26359460 TI - Fas Ligand Deficiency Impairs Tumor Immunity by Promoting an Accumulation of Monocytic Myeloid-Derived Suppressor Cells. AB - The Fas receptor ligand FasL regulates immune cell levels by inducing apoptosis of Fas receptor-positive cells. Here, we studied the impact of host FasL on tumor development in mice. Genetically targeting FasL in naive mice increased myeloid cell populations, but, in marked contrast, it reduced the levels of myeloid derived suppressor cells (MDSC) in mice bearing Lewis lung carcinoma tumors. Analysis of the MDSC subset distribution revealed that FasL deficiency skewed cell populations toward the M-MDSC subset, which displays a highly immunosuppressive activity. Furthermore, tumor-bearing mice that were FasL deficient displayed an enhanced proportion of tumor-associated macrophages and regulatory T cells. Overall, the immunosuppressive environment produced by FasL targeting correlated with reduced survival of tumor-bearing mice. These results disclose a new role for FasL in modulating immunosuppressive cells. PMID- 26359463 TI - Delayed full-thickness macular hole closure without vitreomacular traction release following ocriplasmin injection. AB - We report a case of a 77-year-old Caucasian woman, treated with ocriplasmin injection for vitreomacular traction (VMT) and full-thickness macular hole (FTMH), who had a persistence outer retinal defect on her 28-day review, without VMT resolution, then presented 3 months later with complete macular hole closure, with persistence of vitreomacular adhesion. This case raises the question on the validity of the 28-day fixed date to assess final outcome of ocriplasmin injection for FTMH associated with VMT, and sheds new lights on the behaviour of the posterior hyaloid in cases of vitreolysis by a chemical agent such as ocriplasmin. PMID- 26359464 TI - Palmar-plantar erythrodysesthesia. PMID- 26359465 TI - International Variation in Female Breast Cancer Incidence and Mortality Rates. AB - BACKGROUND: Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer-related death among women worldwide. Herein, we examine global trends in female breast cancer rates using the most up-to-date data available. METHODS: Breast cancer incidence and mortality estimates were obtained from GLOBOCAN 2012 (globocan.iarc.fr). We analyzed trends from 1993 onward using incidence data from 39 countries from the International Agency for Research on Cancer and mortality data from 57 countries from the World Health Organization. RESULTS: Of 32 countries with incidence and mortality data, rates in the recent period diverged-with incidence increasing and mortality decreasing-in nine countries mainly in Northern/Western Europe. Both incidence and mortality decreased in France, Israel, Italy, Norway, and Spain. In contrast, incidence and death rates both increased in Colombia, Ecuador, and Japan. Death rates also increased in Brazil, Egypt, Guatemala, Kuwait, Mauritius, Mexico, and Moldova. CONCLUSIONS: Breast cancer mortality rates are decreasing in most high-income countries, despite increasing or stable incidence rates. In contrast and of concern are the increasing incidence and mortality rates in a number of countries, particularly those undergoing rapid changes in human development. Wide variations in breast cancer rates and trends reflect differences in patterns of risk factors and access to and availability of early detection and timely treatment. IMPACT: Increased awareness about breast cancer and the benefits of early detection and improved access to treatment must be prioritized to successfully implement breast cancer control programs, particularly in transitioning countries. PMID- 26359466 TI - Advancing Care Together by Integrating Primary Care and Behavioral Health. PMID- 26359467 TI - Strategies to Support the Integration of Behavioral Health and Primary Care: What Have We Learned Thus Far? AB - The articles in this supplement contain a wealth of practical information regarding the integration of behavioral health and primary care. This type of integration effort is complex and greatly benefits from support from outside organizations, as well as collaboration with other practices attempting similar work. This editorial extracts from these articles some of the key lessons learned regarding the integration of behavioral health and primary care for practices and for organizations that support practice transformation. PMID- 26359468 TI - Integrated Care: Tools, Maps, and Leadership. PMID- 26359469 TI - Integrating Behavioral Health and Primary Care: Consulting, Coordinating and Collaborating Among Professionals. AB - PURPOSE: This paper sought to describe how clinicians from different backgrounds interact to deliver integrated behavioral and primary health care, and the contextual factors that shape such interactions. METHODS: This was a comparative case study in which a multidisciplinary team used an immersion-crystallization approach to analyze data from observations of practice operations, interviews with practice members, and implementation diaries. The observed practices were drawn from 2 studies: Advancing Care Together, a demonstration project of 11 practices located in Colorado; and the Integration Workforce Study, consisting of 8 practices located across the United States. RESULTS: Primary care and behavioral health clinicians used 3 interpersonal strategies to work together in integrated settings: consulting, coordinating, and collaborating (3Cs). Consulting occurred when clinicians sought advice, validated care plans, or corroborated perceptions of a patient's needs with another professional. Coordinating involved 2 professionals working in a parallel or in a back-and forth fashion to achieve a common patient care goal, while delivering care separately. Collaborating involved 2 or more professionals interacting in real time to discuss a patient's presenting symptoms, describe their views on treatment, and jointly develop a care plan. Collaborative behavior emerged when a patient's care or situation was complex or novel. We identified contextual factors shaping use of the 3Cs, including: time to plan patient care, staffing, employing brief therapeutic approaches, proximity of clinical team members, and electronic health record documenting behavior. CONCLUSION: Primary care and behavioral health clinicians, through their interactions, consult, coordinate, and collaborate with each other to solve patients' problems. Organizations can create integrated care environments that support these collaborations and health professions training programs should equip clinicians to execute all 3Cs routinely in practice. PMID- 26359470 TI - Clinician Staffing, Scheduling, and Engagement Strategies Among Primary Care Practices Delivering Integrated Care. AB - PURPOSE: To examine the interrelationship among behavioral health clinician (BHC) staffing, scheduling, and a primary care practice's approach to delivering integrated care. METHODS: Observational cross-case comparative analysis of 17 primary care practices in the United States focused on implementation of integrated care. Practices varied in size, ownership, geographic location, and integrated care experience. A multidisciplinary team analyzed documents, practice surveys, field notes from observation visits, implementation diaries, and semistructured interviews using a grounded theory approach. RESULTS: Across the 17 practices, staffing ratios ranged from 1 BHC covering 0.3 to 36.5 primary care clinicians (PCCs). BHC scheduling varied from 50-minute prescheduled appointments to open, flexible schedules slotted in 15-minute increments. However, staffing and scheduling patterns generally clustered in 2 ways and enabled BHCs to be engaged by referral or warm handoff. Five practices predominantly used warm handoffs to engage BHCs and had higher BHC-to-PCC staffing ratios; multiple BHCs on staff; and shorter, more flexible BHC appointment schedules. Staffing and scheduling structures that enabled warm handoffs supported BHC engagement with patients concurrent with the identification of behavioral health needs. Twelve practices primarily used referrals to engage BHCs and had lower BHC-to-PCC staffing ratios and BHC schedules prefilled with visits. This enabled some BHCs to bill for services, but also made them less accessible to PCCs in when patients presented with behavioral health needs during a clinical encounter. Three of these practices were experimenting with open scheduling and briefer BHC visits to enable real-time access while managing resources. CONCLUSION: Practices' approaches to PCC-BHC staffing, scheduling, and delivery of integrated care mutually influenced each other and were shaped by the local context. Practice leaders, educators, clinicians, funders, researchers, and policy makers must consider these factors as they seek to optimize integrated systems of care. PMID- 26359471 TI - Preparing the Workforce for Behavioral Health and Primary Care Integration. AB - PURPOSE: To identify how organizations prepare clinicians to work together to integrate behavioral health and primary care. METHODS: Observational cross-case comparison study of 19 U.S. practices, 11 participating in Advancing Care Together, and 8 from the Integration Workforce Study. Practices varied in size, ownership, geographic location, and experience delivering integrated care. Multidisciplinary teams collected data (field notes from direct practice observations, semistructured interviews, and online diaries as reported by practice leaders) and then analyzed the data using a grounded theory approach. RESULTS: Organizations had difficulty finding clinicians possessing the skills and experience necessary for working in an integrated practice. Practices newer to integration underestimated the time and resources needed to train and organizationally socialize (onboard) new clinicians. Through trial and error, practices learned that clinicians needed relevant training to work effectively as integrated care teams. Training efforts exclusively targeting behavioral health clinicians (BHCs) and new employees were incomplete if primary care clinicians (PCCs) and others in the practice also lacked experience working with BHCs and delivering integrated care. Organizations' methods for addressing employees' need for additional preparation included hiring a consultant to provide training, sending employees to external training programs, hosting residency or practicum training programs, or creating their own internal training program. Onboarding new employees through the development of training manuals; extensive shadowing processes; and protecting time for ongoing education, mentoring, and support opportunities for new and established clinicians and staff were featured in these internal training programs. CONCLUSION: Insufficient training capacity and practical experience opportunities continue to be major barriers to supplying the workforce needed for effective behavioral health and primary care integration. Until the training capacity grows to meet the demand, practices must put forth considerable effort and resources to train their own employees. PMID- 26359472 TI - Designing Clinical Space for the Delivery of Integrated Behavioral Health and Primary Care. AB - PURPOSE: This study sought to describe features of the physical space in which practices integrating primary care and behavioral health care work and to identify the arrangements that enable integration of care. METHODS: We conducted an observational study of 19 diverse practices located across the United States. Practice-level data included field notes from 2-4-day site visits, transcripts from semistructured interviews with clinicians and clinical staff, online implementation diary posts, and facility photographs. A multidisciplinary team used a 4-stage, systematic approach to analyze data and identify how physical layout enabled the work of integrated care teams. RESULTS: Two dominant spatial layouts emerged across practices: type-1 layouts were characterized by having primary care clinicians (PCCs) and behavioral health clinicians (BHCs) located in separate work areas, and type-2 layouts had BHCs and PCCs sharing work space. We describe these layouts and the influence they have on situational awareness, interprofessional "bumpability," and opportunities for on-the-fly communication. We observed BHCs and PCCs engaging in more face-to-face methods for coordinating integrated care for patients in type 2 layouts (41.5% of observed encounters vs 11.7%; P < .05). We show that practices needed to strike a balance between professional proximity and private work areas to accomplish job tasks. Private workspace was needed for focused work, to see patients, and for consults between clinicians and clinical staff. We describe the ways practices modified and built new space and provide 2 recommended layouts for practices integrating care based on study findings. CONCLUSION: Physical layout and positioning of professionals' workspace is an important consideration in practices implementing integrated care. Clinicians, researchers, and health-care administrators are encouraged to consider the role of professional proximity and private working space when creating new facilities or redesigning existing space to foster delivery of integrated behavioral health and primary care. PMID- 26359473 TI - Electronic Health Record Challenges, Workarounds, and Solutions Observed in Practices Integrating Behavioral Health and Primary Care. AB - PURPOSE: This article describes the electronic health record (EHR)-related experiences of practices striving to integrate behavioral health and primary care using tailored, evidenced-based strategies from 2012 to 2014; and the challenges, workarounds and initial health information technology (HIT) solutions that emerged during implementation. METHODS: This was an observational, cross-case comparative study of 11 diverse practices, including 8 primary care clinics and 3 community mental health centers focused on the implementation of integrated care. Practice characteristics (eg, practice ownership, federal designation, geographic area, provider composition, EHR system, and patient panel characteristics) were collected using a practice information survey and analyzed to report descriptive information. A multidisciplinary team used a grounded theory approach to analyze program documents, field notes from practice observation visits, online diaries, and semistructured interviews. RESULTS: Eight primary care practices used a single EHR and 3 practices used 2 different EHRs, 1 to document behavioral health and 1 to document primary care information. Practices experienced common challenges with their EHRs' capabilities to 1) document and track relevant behavioral health and physical health information, 2) support communication and coordination of care among integrated teams, and 3) exchange information with tablet devices and other EHRs. Practices developed workarounds in response to these challenges: double documentation and duplicate data entry, scanning and transporting documents, reliance on patient or clinician recall for inaccessible EHR information, and use of freestanding tracking systems. As practices gained experience with integration, they began to move beyond workarounds to more permanent HIT solutions ranging in complexity from customized EHR templates, EHR upgrades, and unified EHRs. CONCLUSION: Integrating behavioral health and primary care further burdens EHRs. Vendors, in cooperation with clinicians, should intentionally design EHR products that support integrated care delivery functions, such as data documentation and reporting to support tracking patients with emotional and behavioral problems over time and settings, integrated teams working from shared care plans, template-driven documentation for common behavioral health conditions such as depression, and improved registry functionality and interoperability. This work will require financial support and cooperative efforts among clinicians, EHR vendors, practice assistance organizations, regulators, standards setters, and workforce educators. PMID- 26359474 TI - Understanding Care Integration from the Ground Up: Five Organizing Constructs that Shape Integrated Practices. AB - PURPOSE: To provide empirical evidence on key organizing constructs shaping practical, real-world integration of behavior health and primary care to comprehensively address patients' medical, emotional, and behavioral health needs. METHODS: In a comparative case study using an immersion-crystallization approach, a multidisciplinary team analyzed data from observations of practice operations, interviews, and surveys of practice members, and implementation diaries. Practices were drawn from 2 studies of practices attempting to integrate behavioral health and primary care: Advancing Care Together, a demonstration project of 11 practices located in Colorado, and the Integration Workforce Study, a study of 8 practices across the United States. RESULTS: We identified 5 key organizing constructs influencing integration of primary care and behavioral health: 1) Integration REACH (the extent to which the integration program was delivered to the identified target population), 2) establishment of continuum of care pathways addressing the location of care across the range of patient's severity of illness, 3) approach to patient transitions: referrals or warm handoffs, 4) location of the integration workforce, and 5) participants' mental model for integration. These constructs intertwine within an organization's historic and social context to produce locally adapted approaches to integrating care. Contextual factors, particularly practice type, influenced whether specialty mental health and substance use services were colocated within an organization. CONCLUSION: Interaction among 5 organizing constructs and practice context produces diverse expressions of integrated care. These constructs provide a framework for understanding how primary care and behavioral health services can be integrated in routine practice. PMID- 26359475 TI - REACH of Interventions Integrating Primary Care and Behavioral Health. AB - PURPOSE: This study reports REACH (the extent to which an intervention or program was delivered to the identified target population) of interventions integrating primary care and behavioral health implemented by real-world practices. METHODS: Eleven practices implementing integrated care interventions provided data to calculate REACH as follows: 1) Screening REACH defined as proportion of target patients assessed for integrated care, and 2) Integrated care services REACH defined as proportion of patients receiving integrated services of those who met specific criteria. Difference in mean REACH between practices was evaluated using t test. RESULTS: Overall, 26.2% of target patients (n = 24,906) were assessed for integrated care and 41% (n = 836) of eligible patients received integration services. Practices that implemented systematic protocols to identify patients needing integrated care had a significantly higher screening REACH (mean, 70%; 95% CI [confidence interval], 46.6-93.4%) compared with practices that used clinicians' discretion (mean, 7.9%; 95% CI, 0.6-15.1; P = .0014). Integrated care services REACH was higher among practices that used clinicians' discretion compared with those that assessed patients systematically (mean, 95.8 vs 53.8%; P = .03). CONCLUSION: REACH of integrated care interventions differed by practices' method of assessing patients. Measuring REACH is important to evaluate the extent to which integration efforts affect patient care and can help demonstrate the impact of integrated care to payers and policy makers. PMID- 26359476 TI - Start-Up and Ongoing Practice Expenses of Behavioral Health and Primary Care Integration Interventions in the Advancing Care Together (ACT) Program. AB - PURPOSE: Provide credible estimates of the start-up and ongoing effort and incremental practice expenses for the Advancing Care Together (ACT) behavioral health and primary care integration interventions. METHODS: Expenditure data were collected from 10 practice intervention sites using an instrument with a standardized general format that could accommodate the unique elements of each intervention. RESULTS: Average start-up effort expenses were $44,076 and monthly ongoing effort expenses per patient were $40.39. Incremental expenses averaged $20,788 for start-up and $4.58 per patient for monthly ongoing activities. Variations in expenditures across practices reflect the differences in intervention specifics and organizational settings. Differences in effort to incremental expenditures reflect the extensive use of existing resources in implementing the interventions. CONCLUSIONS: ACT program incremental expenses suggest that widespread adoption would likely have a relatively modest effect on overall health systems expenditures. Practice effort expenses are not trivial and may pose barriers to adoption. Payers and purchasers interested in attaining widespread adoption of integrated care must consider external support to practices that accounts for both incremental and effort expense levels. Existing knowledge transfer mechanisms should be employed to minimize developmental start up expenses and payment reform focused toward value-based, Triple Aim-oriented reimbursement and purchasing mechanisms are likely needed. PMID- 26359477 TI - When Frontline Practice Innovations Are Ahead of the Health Policy Community: The Example of Behavioral Health and Primary Care Integration. AB - Innovation in health care delivery often far outpaces the speed at which health policy changes to accommodate this innovation. Integrating behavioral health and primary care is a promising approach to defragment health care and help health care achieve the triple aim of decreasing costs, improving outcomes, and enhancing patients' experiences. However, the problem remains that health policy does not frequently support the integration of care. This commentary describes some of the reasons policy falters as well as potential opportunities to begin to influence health policy to better support practices that take an integrated approach to health care. PMID- 26359478 TI - Association of Influenza Vaccination Coverage in Younger Adults With Influenza Related Illness in the Elderly. AB - BACKGROUND: Older adults have the highest influenza-related morbidity and mortality risk, but the influenza vaccine is less effective in the elderly. It is unknown whether influenza vaccination of nonelderly adults confers additional disease protection on the elderly population. METHODS: We examined the association between county-wide influenza vaccination coverage among 520 229 younger adults (aged 18-64 years) in the Behavioral Risk Factors Surveillance System Survey and illnesses related to influenza in 3 317 709 elderly Medicare beneficiaries aged >=65 years, between 2002 and 2010 (13 267 786 person-years). Results were stratified by documented receipt of a seasonal influenza vaccine in each Medicare beneficiary. RESULTS: Increases in county-wide vaccine coverage among younger adults were associated with lower adjusted odds of illnesses related to influenza in the elderly. Compared with elderly residents of counties with <=15% of younger adults vaccinated, the adjusted odds ratio for a principal diagnosis of influenza among elderly residents was 0.91 (95% confidence interval, .88-.94) for counties with 16%-20% of younger adults vaccinated, 0.87 (.84-.90) for counties with 21%-25% vaccinated, 0.80 (.77-.83) for counties with 26%-30% vaccinated, and 0.79 (.76-.83) for counties with >=31% vaccinated (P for trend <.001). Stronger associations were observed among vaccinated elderly adults, in peak months of influenza season, in more severe influenza seasons, in influenza seasons with greater antigenic match to influenza vaccine, and for more specific definitions of influenza-related illness. CONCLUSIONS: In a large, nationwide sample of Medicare beneficiaries, influenza vaccination among adults aged 18-64 years was inversely associated with illnesses related to influenza in the elderly. PMID- 26359479 TI - Mechanisms for the Termination of Atrial Fibrillation by Localized Ablation: Computational and Clinical Studies. AB - BACKGROUND: Human atrial fibrillation (AF) can terminate after ablating localized regions, which supports the existence of localized rotors (spiral waves) or focal drivers. However, it is unclear why ablation near a spiral wave tip would terminate AF and not anchor reentry. We addressed this question by analyzing competing mechanisms for AF termination in numeric simulations, referenced to clinical observations. METHODS AND RESULTS: Spiral wave reentry was simulated in monodomain 2-dimensional myocyte sheets using clinically realistic rate-dependent values for repolarization and conduction. Heterogeneous models were created by introduction of parameterized variations in tissue excitability. Ablation lesions were applied as nonconducting circular regions. Models confirmed that localized ablation may anchor spiral wave reentry, producing organized tachycardias. Several mechanisms referenced to clinical observations explained termination of AF to sinus rhythm. First, lesions may create an excitable gap vulnerable to invasion by fibrillatory waves. Second, ablation of rotors in regions of low excitability (from remodeling) produced re-entry in more excitable tissue allowing collision of wavefront and back. Conversely, ablation of rotors in high excitability regions migrated spiral waves to less excitable tissue, where they detached to collide with nonconducting boundaries. Third, ablation may connect rotors to nonconducting anatomic orifices. Fourth, reentry through slow conducting channels may terminate if ablation closes these channels. CONCLUSIONS: Limited ablation can terminate AF by several mechanisms. These data shed light on how clinical AF may be sustained in patients' atria, emphasizing heterogeneities in tissue excitability, slow-conducting channels, and obstacles that are increasingly detectable in patients and should be the focus of future translational studies. PMID- 26359480 TI - Irrigated Needle Ablation Creates Larger and More Transmural Ventricular Lesions Compared With Standard Unipolar Ablation in an Ovine Model. AB - BACKGROUND: Ventricular tachycardia recurrence can occur after ventricular tachycardia ablation because of incomplete and nontransmural ventricular lesion formation. We sought to compare the lesions made by a novel irrigated needle catheter to conventional radiofrequency lesions. METHODS AND RESULTS: Thirteen female sheep (4.6+/-0.7 years, 54+/-8 kg) were studied. In 7 sheep, 60-s radiofrequency applications were performed using an irrigated needle catheter. In 6 sheep, conventional lesions were made using a 4-mm irrigated catheter. 1.5T in vivo and high-density magnetic resonance imaging (9.4T) were performed on explanted hearts from animals receiving needle radiofrequency. Conventional lesion volume was calculated as (1/6)*pi*(A*B(2)+C*D(2)/2). Needle lesion volume was measured as Sigma(pi*r(2))/2 with a slice thickness of 1 mm. The dimensions of all lesions were also measured on gross pathology. Additional histological analysis of the needle lesions was performed. One hundred twenty endocardial left ventricular ablation lesions (conventional, n=60; needle, n=60) were created. At necropsy, more lesions were found using needle versus conventional radiofrequency (90% versus 75%; P<0.05). Comparing needle versus conventional radiofrequency: lesion volume was larger (1030+/-362 versus 488+/-384 mm(3); P<0.001), lesion depth was increased (9.9+/-2.7 versus 5+/-2.4 mm; P<0.001), and more transmural lesions were created (62.5% versus 17%; P<0.01). Pericardial contrast injection was observed in 4 apical attempts using needle radiofrequency, however, with no adverse effects. Steam pops occurred in 3 attempts using conventional radiofrequency. CONCLUSIONS: Irrigated needle ablation is associated with more frequent, larger, deeper, and more often transmural lesions compared with conventional irrigated ablation. This technology might be of value to treat intramural or epicardial ventricular tachycardia substrates resistant to conventional ablation. PMID- 26359481 TI - AT1 receptor blocker losartan protects against mechanical ventilation-induced diaphragmatic dysfunction. AB - Mechanical ventilation is a life-saving intervention for patients in respiratory failure. Unfortunately, prolonged ventilator support results in diaphragmatic atrophy and contractile dysfunction leading to diaphragm weakness, which is predicted to contribute to problems in weaning patients from the ventilator. While it is established that ventilator-induced oxidative stress is required for the development of ventilator-induced diaphragm weakness, the signaling pathway(s) that trigger oxidant production remain unknown. However, recent evidence reveals that increased plasma levels of angiotensin II (ANG II) result in oxidative stress and atrophy in limb skeletal muscles. Using a well established animal model of mechanical ventilation, we tested the hypothesis that increased circulating levels of ANG II are required for both ventilator-induced diaphragmatic oxidative stress and diaphragm weakness. Cause and effect was determined by administering an angiotensin-converting enzyme inhibitor (enalapril) to prevent ventilator-induced increases in plasma ANG II levels, and the ANG II type 1 receptor antagonist (losartan) was provided to prevent the activation of ANG II type 1 receptors. Enalapril prevented the increase in plasma ANG II levels but did not protect against ventilator-induced diaphragmatic oxidative stress or diaphragm weakness. In contrast, losartan attenuated both ventilator-induced oxidative stress and diaphragm weakness. These findings indicate that circulating ANG II is not essential for the development of ventilator-induced diaphragm weakness but that activation of ANG II type 1 receptors appears to be a requirement for ventilator-induced diaphragm weakness. Importantly, these experiments provide the first evidence that the Food and Drug Administration-approved drug losartan may have clinical benefits to protect against ventilator-induced diaphragm weakness in humans. PMID- 26359482 TI - Effects of serotonergic agents on respiratory recovery after cervical spinal injury. AB - Unilateral cervical spinal cord hemisection (i.e., C2Hx) usually interrupts the bulbospinal respiratory pathways and results in respiratory impairment. It has been demonstrated that activation of the serotonin system can promote locomotor recovery after spinal cord injury. The present study was designed to investigate whether serotonergic activation can improve respiratory function during the chronic injury state. Bilateral diaphragm electromyogram and tidal volume were measured in anesthetized and spontaneously breathing adult rats at 8 wk post-C2Hx or C2 laminectomy. A bolus intravenous injection of a serotonin precursor [5 hydroxytryptophan (5-HTP), 10 mg/kg], a serotonin reuptake inhibitor (fluoxetine, 10 mg/kg), or a potent agonist for serotonin 2A receptors (TCB-2, 0.05 mg/kg) was used to activate the serotonergic system. Present results demonstrated that 5-HTP and TCB-2, but not fluoxetine, significantly increased the inspiratory activity of the diaphragm electromyogram ipsilateral to the lesion for at least 30 min in C2Hx animals, but not in animals that received sham surgery. However, the tidal volume was not increased after administration of 5-HTP or TCB-2, indicating that the enhancement of ipsilateral diaphragm activity is not associated with improvement of the tidal volume. These results suggest that exogenous activation of the serotonergic system can specifically enhance the ipsilateral diaphragmatic motor outputs, but this approach may not be sufficient to improve respiratory functional recovery following chronic cervical spinal injury. PMID- 26359483 TI - Dysanapsis and the resistive work of breathing during exercise in healthy men and women. AB - We asked if the higher work of breathing (Wb) during exercise in women compared with men is explained by biological sex. We created a statistical model that accounts for both the viscoelastic and the resistive components of the total Wb and independently compares the effects of biological sex. We applied the model to esophageal pressure-derived Wb values obtained during an incremental cycle test to exhaustion. Subjects were healthy men (n = 17) and women (n = 18) with a range of maximal aerobic capacities (Vo2 max range: men = 40-68 and women = 39-60 ml.kg(-1).min(-1)). We also calculated the dysanapsis ratio using measures of lung recoil and forced expiratory flow as index of airway caliber. By applying the model we found that the differences in the total Wb during exercise in women are due to a higher resistive Wb rather than viscoelastic Wb. We also found that the higher resistive Wb is independently explained by biological sex. To account for the known effect of lung volumes on the dysanapsis ratio we compared the sexes with an analysis of covariance procedures and found that when vital capacity was accounted for the adjusted mean dysanapsis ratio is statistically lower in women (0.17 vs. 0.25 arbitrary units; P < 0.05). Our collective findings suggest that innate sex-based differences may exist in human airways, which result in significant male-female differences in the Wb during exercise in healthy subjects. PMID- 26359484 TI - Effects of ischemic preconditioning on maximal constant-load cycling performance. AB - This study investigated the effects of ischemic preconditioning (IPC) on the ratings of perceived exertion (RPE), surface electromyography, and pulmonary oxygen uptake (Vo2) onset kinetics during cycling until exhaustion at the peak power output attained during an incremental test. A group of 12 recreationally trained cyclists volunteered for this study. After determination of peak power output during an incremental test, they were randomly subjected on different days to a performance protocol preceded by intermittent bilateral cuff pressure inflation to 220 mmHg (IPC) or 20 mmHg (control). To increase data reliability, the performance visits were replicated, also in a random manner. There was an 8.0% improvement in performance after IPC (control: 303 s, IPC 327 s, factor SDs of *//1.13, P = 0.01). This change was followed by a 2.9% increase in peak Vo2 (control: 3.95 l/min, IPC: 4.06 l/min, factor SDs of *//1.15, P = 0.04), owing to a higher amplitude of the slow component of the Vo2 kinetics (control: 0.45 l/min, IPC: 0.63 l/min, factor SDs of *//2.21, P = 0.05). There was also an attenuation in the rate of increase in RPE (P = 0.01) and a progressive increase in the myoelectrical activity of the vastus lateralis muscle (P = 0.04). Furthermore, the changes in peak Vo2 (r = 0.73, P = 0.007) and the amplitude of the slow component (r = 0.79, P = 0.002) largely correlated with performance improvement. These findings provide a link between improved aerobic metabolism and enhanced severe-intensity cycling performance after IPC. Furthermore, the delayed exhaustion after IPC under lower RPE and higher skeletal muscle activation suggest they have a role on the ergogenic effects of IPC on endurance performance. PMID- 26359485 TI - Intestinal epithelial barrier function and tight junction proteins with heat and exercise. AB - A single layer of enterocytes and tight junctions (intercellular multiprotein complexes) form the intestinal epithelial barrier that controls transport of molecules through transcellular and paracellular pathways. A dysfunctional or "leaky" intestinal tight junction barrier allows augmented permeation of luminal antigens, endotoxins, and bacteria into the blood stream. Various substances and conditions have been shown to affect the maintenance of the intestinal epithelial tight junction barrier. The primary focus of the present review is to analyze the effects of exertional or nonexertional (passive hyperthermia) heat stress on tight junction barrier function in in vitro and in vivo (animals and humans) models. Our secondary focus is to review changes in tight junction proteins in response to exercise or hyperthermic conditions. Finally, we discuss some pharmacological or nutritional interventions that may affect the cellular mechanisms involved in maintaining homeostasis of the intestinal epithelial tight junction barrier during heat stress or exercise. PMID- 26359486 TI - Triple Quad-ICP-MS Measurement of Toxic Metals in Mainstream Cigarette Smoke from Spectrum Research Cigarettes. AB - We previously reported toxic metal concentrations in the mainstream smoke from 50 varieties of commercial cigarettes available in the USA using quadrupole inductively coupled plasma-mass spectrometry (ICP-MS). However, efforts to continue producing high quality data on select mainstream cigarette smoke constituents demand continued improvements in instrumentation and methodology and application of the methodology to cigarettes that differ in design or construction. Here we report a new application of 'triple quad'-ICP-MS instrumentation to analyze seven toxic metals in mainstream cigarette smoke from the Spectrum variable nicotine research cigarettes. The Spectrum cigarettes are available for research purposes in different configurations of low or conventional levels of nicotine, mentholated or nonmentholated, and tar delivery ranges described as 'low tar' or 'high tar'. Detailed characterizations of specific harmful or potentially harmful constituents delivered by these research cigarettes will help inform researchers using these cigarettes in exposure studies, cessation studies and studies related to nicotine addiction or compensation. PMID- 26359487 TI - 2015 Gout classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. AB - OBJECTIVE: Existing criteria for the classification of gout have suboptimal sensitivity and/or specificity, and were developed at a time when advanced imaging was not available. The current effort was undertaken to develop new classification criteria for gout. METHODS: An international group of investigators, supported by the American College of Rheumatology and the European League Against Rheumatism, conducted a systematic review of the literature on advanced imaging of gout, a diagnostic study in which the presence of monosodium urate monohydrate (MSU) crystals in synovial fluid or tophus was the gold standard, a ranking exercise of paper patient cases, and a multi-criterion decision analysis exercise. These data formed the basis for developing the classification criteria, which were tested in an independent data set. RESULTS: The entry criterion for the new classification criteria requires the occurrence of at least one episode of peripheral joint or bursal swelling, pain, or tenderness. The presence of MSU crystals in a symptomatic joint/bursa (ie, synovial fluid) or in a tophus is a sufficient criterion for classification of the subject as having gout, and does not require further scoring. The domains of the new classification criteria include clinical (pattern of joint/bursa involvement, characteristics and time course of symptomatic episodes), laboratory (serum urate, MSU-negative synovial fluid aspirate), and imaging (double-contour sign on ultrasound or urate on dual-energy CT, radiographic gout-related erosion). The sensitivity and specificity of the criteria are high (92% and 89%, respectively). CONCLUSIONS: The new classification criteria, developed using a data-driven and decision-analytic approach, have excellent performance characteristics and incorporate current state-of-the-art evidence regarding gout. PMID- 26359489 TI - Current evidence for therapeutic interventions and prognostic factors in polymyalgia rheumatica: a systematic literature review informing the 2015 European League Against Rheumatism/American College of Rheumatology recommendations for the management of polymyalgia rheumatica. AB - To summarise evidence on therapeutic interventions and prognostic factors in polymyalgia rheumatica (PMR). A systematic literature review was conducted using Ovid Medline, Embase, PubMed, CINAHL, Web of Science and the Cochrane Library (1970 through April 2014). Quality of evidence (QoE) of identified studies was appraised by Grading of Recommendations Assessment, Development and Evaluation (GRADE) (interventions) and the Quality In Prognosis Studies (QUIPS) methodologies (prognostic factors). Out of 10 931 titles identified, 52 articles were finally selected. A single study indicated that an initial prednisone dose of 20 mg/day is associated with a lower short-term relapse rate than 10 mg/day but at the cost of a higher rate of adverse events. Another study suggested a comparable efficacy of intramuscular methylprednisolone and oral glucocorticoids (GCs) with lower cumulative GC doses and less weight gain in the former group. Moderate to high QoE (1-2 studies) indicated a benefit of methotrexate in remission rates and cumulative GC doses in early PMR. Anti-tumour necrosis factor alpha agents are ineffective for PMR treatment. Among prognostic factors, female sex, high erythrocyte sedimentation rate (ESR) and peripheral arthritis were associated in some studies with a higher relapse risk. Women and patients with high ESR also appeared to have a longer duration of treatment. Several studies of varying quality, however, failed to prove these associations. In PMR, evidence for initial GC doses and subsequent tapering regimens is limited. Intramuscular methylprednisolone and methotrexate may be effective GC sparing agents. Female sex, high ESR and peripheral arthritis at disease outset are potential risk factors for a worse prognosis. PMID- 26359488 TI - 2015 Recommendations for the management of polymyalgia rheumatica: a European League Against Rheumatism/American College of Rheumatology collaborative initiative. AB - Therapy for polymyalgia rheumatica (PMR) varies widely in clinical practice as international recommendations for PMR treatment are not currently available. In this paper, we report the 2015 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) recommendations for the management of PMR. We used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology as a framework for the project. Accordingly, the direction and strength of the recommendations are based on the quality of evidence, the balance between desirable and undesirable effects, patients' and clinicians' values and preferences, and resource use. Eight overarching principles and nine specific recommendations were developed covering several aspects of PMR, including basic and follow-up investigations of patients under treatment, risk factor assessment, medical access for patients and specialist referral, treatment strategies such as initial glucocorticoid (GC) doses and subsequent tapering regimens, use of intramuscular GCs and disease modifying anti rheumatic drugs (DMARDs), as well as the roles of non-steroidal anti-rheumatic drugs and non-pharmacological interventions. These recommendations will inform primary, secondary and tertiary care physicians about an international consensus on the management of PMR. These recommendations should serve to inform clinicians about best practices in the care of patients with PMR. PMID- 26359490 TI - Climatic niche and flowering and fruiting phenology of an epiphytic plant. AB - Species have geographic distributions constrained by combinations of abiotic factors, biotic factors and dispersal-related factors. Abiotic requirements vary across the life stages for a species; for plant species, a particularly important life stage is when the plant flowers and develops seeds. A previous year-long experiment showed that ambient temperature of 5-35 degrees C, relative humidity of >50 % and <=15 consecutive rainless days are crucial abiotic conditions for Spanish moss (Tillandsia usneoides L.). Here, we explore whether these optimal physiological intervals relate to the timing of the flowering and fruiting periods of Spanish moss across its range. As Spanish moss has a broad geographic range, we examined herbarium specimens to detect and characterize flowering/fruiting periods for the species across the Americas; we used high temporal-resolution climatic data to assess the availability of optimal conditions for Spanish moss populations during each population's flowering period. We explored how long populations experience suboptimal conditions and found that most populations experience suboptimal conditions in at least one environmental dimension. Flowering and fruiting periods of Spanish moss populations are either being optimized for one or a few parameters or may be adjusted such that all parameters are suboptimal. Spanish moss populations appear to be constrained most closely by minimum temperature during this period. PMID- 26359491 TI - Combinatorial and Computational Approaches to Identify Interactions of Macrophage Colony-stimulating Factor (M-CSF) and Its Receptor c-FMS. AB - The molecular interactions between macrophage colony-stimulating factor (M-CSF) and the tyrosine kinase receptor c-FMS play a key role in the immune response, bone metabolism, and the development of some cancers. Because no x-ray structure is available for the human M-CSF . c-FMS complex, the binding epitope for this complex is largely unknown. Our goal was to identify the residues that are essential for binding of the human M-CSF to c-FMS. For this purpose, we used a yeast surface display (YSD) approach. We expressed a combinatorial library of monomeric M-CSF (M-CSFM) single mutants and screened this library to isolate variants with reduced affinity for c-FMS using FACS. Sequencing yielded a number of single M-CSFM variants with mutations both in the direct binding interface and distant from the binding site. In addition, we used computational modeling to map the identified mutations onto the M-CSFM structure and to classify the mutations into three groups as follows: those that significantly decrease protein stability; those that destroy favorable intermolecular interactions; and those that decrease affinity through allosteric effects. To validate the YSD and computational data, M-CSFM and three variants were produced as soluble proteins; their affinity and structure were analyzed; and very good correlations with both YSD data and computational predictions were obtained. By identifying the M-CSFM residues critical for M-CSF . c-FMS interactions, we have laid down the basis for a deeper understanding of the M-CSF . c-FMS signaling mechanism and for the development of target-specific therapeutic agents with the ability to sterically occlude the M-CSF.c-FMS binding interface. PMID- 26359492 TI - Structural and functional studies of the Pseudomonas aeruginosa minor pilin, PilE. AB - Many bacterial pathogens, including Pseudomonas aeruginosa, use type IVa pili (T4aP) for attachment and twitching motility. T4aP are composed primarily of major pilin subunits, which are repeatedly assembled and disassembled to mediate function. A group of pilin-like proteins, the minor pilins FimU and PilVWXE, prime pilus assembly and are incorporated into the pilus. We showed previously that minor pilin PilE depends on the putative priming subcomplex PilVWX and the non-pilin protein PilY1 for incorporation into pili, and that with FimU, PilE may couple the priming subcomplex to the major pilin PilA, allowing for efficient pilus assembly. Here we provide further support for this model, showing interaction of PilE with other minor pilins and the major pilin. A 1.25 A crystal structure of PilEDelta1-28 shows a typical type IV pilin fold, demonstrating how it may be incorporated into the pilus. Despite limited sequence identity, PilE is structurally similar to Neisseria meningitidis minor pilins PilXNm and PilVNm, recently suggested via characterization of mCherry fusions to modulate pilus assembly from within the periplasm. A P. aeruginosa PilE-mCherry fusion failed to complement twitching motility or piliation of a pilE mutant. However, in a retraction-deficient strain where surface piliation depends solely on PilE, the fusion construct restored some surface piliation. PilE-mCherry was present in sheared surface fractions, suggesting that it was incorporated into pili. Together, these data provide evidence that PilE, the sole P. aeruginosa equivalent of PilXNm and PilVNm, likely connects a priming subcomplex to the major pilin, promoting efficient assembly of T4aP. PMID- 26359493 TI - Saturation Mutagenesis of the Antithrombin Reactive Center Loop P14 Residue Supports a Three-step Mechanism of Heparin Allosteric Activation Involving Intermediate and Fully Activated States. AB - Past studies have suggested that a key feature of the mechanism of heparin allosteric activation of the anticoagulant serpin, antithrombin, is the release of the reactive center loop P14 residue from a native state stabilizing interaction with the hydrophobic core. However, more recent studies have indicated that this structural change plays a secondary role in the activation mechanism. To clarify this role, we expressed and characterized 15 antithrombin P14 variants. The variants exhibited basal reactivities with factors Xa and IXa, heparin affinities and thermal stabilities that were dramatically altered from wild type, consistent with the P14 mutations perturbing native state stability and shifting an allosteric equilibrium between native and activated states. Rapid kinetic studies confirmed that limiting rate constants for heparin allosteric activation of the mutants were altered in conjunction with the observed shifts of the allosteric equilibrium. However, correlations of the P14 mutations' effects on parameters reflecting the allosteric activation state of the serpin were inconsistent with a two-state model of allosteric activation and suggested multiple activated states. Together, these findings support a minimal three-state model of allosteric activation in which the P14 mutations perturb equilibria involving distinct native, intermediate, and fully activated states wherein the P14 residue retains an interaction with the hydrophobic core in the intermediate state but is released from the core in the fully activated state, and the bulk of allosteric activation has occurred in the intermediate. PMID- 26359494 TI - Phosphorylation of Serine 402 Regulates RacGAP Protein Activity of FilGAP Protein. AB - FilGAP is a Rho GTPase-activating protein (GAP) that specifically regulates Rac. FilGAP is phosphorylated by ROCK, and this phosphorylation stimulates its RacGAP activity. However, it is unclear how phosphorylation regulates cellular functions and localization of FilGAP. We found that non-phosphorylatable FilGAP (ST/A) mutant is predominantly localized to the cytoskeleton along actin filaments and partially co-localized with vinculin around cell periphery, whereas phosphomimetic FilGAP (ST/D) mutant is diffusely cytoplasmic. Moreover, phosphorylated FilGAP detected by Phos-tag is also mainly localized in the cytoplasm. Of the six potential phosphorylation sites in FilGAP tested, only mutation of serine 402 to alanine (S402A) resulted in decreased cell spreading on fibronectin. FilGAP phosphorylated at Ser-402 is localized to the cytoplasm but not at the cytoskeleton. Although Ser-402 is highly phosphorylated in serum starved quiescent cells, dephosphorylation of Ser-402 is accompanied with the cell spreading on fibronectin. Treatment of the cells expressing wild-type FilGAP with calyculin A, a Ser/Thr phosphatase inhibitor, suppressed cell spreading on fibronectin, whereas cells transfected with FilGAP S402A mutant were not affected by calyculin A. Expression of constitutively activate Arf6 Q67L mutant stimulated membrane blebbing activity of both non-phosphorylatable (ST/A) and phosphomimetic (ST/D) FilGAP mutants. Conversely, depletion of endogenous Arf6 suppressed membrane blebbing induced by FilGAP (ST/A) and (ST/D) mutants. Our study suggests that Arf6 and phosphorylation of FilGAP may regulate FilGAP, and phosphorylation of Ser-402 may play a role in the regulation of cell spreading on fibronectin. PMID- 26359495 TI - The Q-soluble N-Ethylmaleimide-sensitive Factor Attachment Protein Receptor (Q SNARE) SNAP-47 Regulates Trafficking of Selected Vesicle-associated Membrane Proteins (VAMPs). AB - SNAREs constitute the core machinery of intracellular membrane fusion, but vesicular SNAREs localize to specific compartments via largely unknown mechanisms. Here, we identified an interaction between VAMP7 and SNAP-47 using a proteomics approach. We found that SNAP-47 mainly localized to cytoplasm, the endoplasmic reticulum (ER), and ERGIC and could also shuttle between the cytoplasm and the nucleus. SNAP-47 preferentially interacted with the trans-Golgi network VAMP4 and post-Golgi VAMP7 and -8. SNAP-47 also interacted with ER and Golgi syntaxin 5 and with syntaxin 1 in the absence of Munc18a, when syntaxin 1 is retained in the ER. A C-terminally truncated SNAP-47 was impaired in interaction with VAMPs and affected their subcellular distribution. SNAP-47 silencing further shifted the subcellular localization of VAMP4 from the Golgi apparatus to the ER. WT and mutant SNAP-47 overexpression impaired VAMP7 exocytic activity. We conclude that SNAP-47 plays a role in the proper localization and function of a subset of VAMPs likely via regulation of their transport through the early secretory pathway. PMID- 26359496 TI - Eisosomes Regulate Phosphatidylinositol 4,5-Bisphosphate (PI(4,5)P2) Cortical Clusters and Mitogen-activated Protein (MAP) Kinase Signaling upon Osmotic Stress. AB - Eisosomes are multiprotein structures that generate linear invaginations at the plasma membrane of yeast cells. The core component of eisosomes, the BAR domain protein Pil1, generates these invaginations through direct binding to lipids including phosphoinositides. Eisosomes promote hydrolysis of phosphatidylinositol 4,5 bisphosphate (PI(4,5)P2) by functioning with synaptojanin, but the cellular processes regulated by this pathway have been unknown. Here, we found that PI(4,5)P2 regulation by eisosomes inhibits the cell integrity pathway, a conserved MAPK signal transduction cascade. This pathway is activated by multiple environmental conditions including osmotic stress in the fission yeast Schizosaccharomyces pombe. Activation of the MAPK Pmk1 was impaired by mutations in the phosphatidylinositol (PI) 5-kinase Its3, but this defect was suppressed by removal of eisosomes. Using fluorescent biosensors, we found that osmotic stress induced the formation of PI(4,5)P2 clusters that were spatially organized by eisosomes in both fission yeast and budding yeast cells. These cortical clusters contained the PI 5-kinase Its3 and did not assemble in the its3-1 mutant. The GTPase Rho2, an upstream activator of Pmk1, also co-localized with PI(4,5)P2 clusters under osmotic stress, providing a molecular link between these novel clusters and MAPK activation. Our findings have revealed that eisosomes regulate activation of MAPK signal transduction through the organization of cortical lipid based microdomains. PMID- 26359497 TI - Structural insights into cargo recognition by the yeast PTS1 receptor. AB - The peroxisomal matrix protein import is facilitated by cycling import receptors that shuttle between the cytosol and the peroxisomal membrane. The import receptor Pex5p mediates the import of proteins harboring a peroxisomal targeting signal of type I (PTS1). Purified recombinant Pex5p forms a dimeric complex with the PTS1-protein Pcs60p in vitro with a KD of 0.19 MUm. To analyze the structural basis for receptor-cargo recognition, the PTS1 and adjacent amino acids of Pcs60p were systematically scanned for Pex5p binding by an in vitro site-directed photo cross-linking approach. The cross-linked binding regions of the receptor were subsequently identified by high resolution mass spectrometry. Most cross-links were found with TPR6, TPR7, as well as the 7C-loop of Pex5p. Surface plasmon resonance analysis revealed a bivalent interaction mode for Pex5p and Pcs60p. Interestingly, Pcs60p lacking its C-terminal tripeptide sequence was efficiently cross-linked to the same regions of Pex5p. The KD value of the interaction of truncated Pcs60p and Pex5p was in the range of 7.7 MUm. Isothermal titration calorimetry and surface plasmon resonance measurements revealed a monovalent binding mode for the interaction of Pex5p and Pcs60p lacking the PTS1. Our data indicate that Pcs60p contains a second contact site for its receptor Pex5p, beyond the C-terminal tripeptide. The physiological relevance of the ancillary binding region was supported by in vivo import studies. The bivalent binding mode might be explained by a two-step concept as follows: first, cargo recognition and initial tethering by the PTS1-receptor Pex5p; second, lock-in of receptor and cargo. PMID- 26359498 TI - Shedding of Endogenous Interleukin-6 Receptor (IL-6R) Is Governed by A Disintegrin and Metalloproteinase (ADAM) Proteases while a Full-length IL-6R Isoform Localizes to Circulating Microvesicles. AB - Generation of the soluble interleukin-6 receptor (sIL-6R) is a prerequisite for pathogenic IL-6 trans-signaling, which constitutes a distinct signaling pathway of the pleiotropic cytokine interleukin-6 (IL-6). Although in vitro experiments using ectopically overexpressed IL-6R and candidate proteases revealed major roles for the metalloproteinases ADAM10 and ADAM17 in IL-6R shedding, the identity of the protease(s) cleaving IL-6R in more physiological settings, or even in vivo, remains unknown. By taking advantage of specific pharmacological inhibitors and primary cells from ADAM-deficient mice we established that endogenous IL-6R of both human and murine origin is shed by ADAM17 in an induced manner, whereas constitutive release of endogenous IL-6R is largely mediated by ADAM10. Although circulating IL-6R levels are altered in various diseases, the origin of blood-borne IL-6R is still poorly understood. It has been shown previously that ADAM17 hypomorphic mice exhibit unaltered levels of serum sIL-6R. Here, by quantification of serum sIL-6R in protease-deficient mice as well as human patients we also excluded ADAM10, ADAM8, neutrophil elastase, cathepsin G, and proteinase 3 from contributing to circulating sIL-6R. Furthermore, we ruled out alternative splicing of the IL-6R mRNA as a potential source of circulating sIL-6R in the mouse. Instead, we found full-length IL-6R on circulating microvesicles, establishing microvesicle release as a novel mechanism for sIL-6R generation. PMID- 26359499 TI - Structural and Functional Characterization of the JH2 Pseudokinase Domain of JAK Family Tyrosine Kinase 2 (TYK2). AB - JAK (Janus family of cytoplasmic tyrosine kinases) family tyrosine kinase 2 (TYK2) participates in signaling through cytokine receptors involved in immune responses and inflammation. JAKs are characterized by dual kinase domain: a tyrosine kinase domain (JH1) that is preceded by a pseudokinase domain (JH2). The majority of disease-associated mutations in JAKs map to JH2, demonstrating its central regulatory function. JH2s were considered catalytically inactive, but JAK2 JH2 was found to have low autoregulatory catalytic activity. Whether the other JAK JH2s share ATP binding and enzymatic activity has been unclear. Here we report the crystal structure of TYK2 JH2 in complex with adenosine 5'-O (thiotriphosphate) (ATP-gammaS) and characterize its nucleotide binding by biochemical and biophysical methods. TYK2 JH2 did not show phosphotransfer activity, but it binds ATP and the nucleotide binding stabilizes the protein without inducing major conformational changes. Mutation of the JH2 ATP-binding pocket increased basal TYK2 phosphorylation and downstream signaling. The overall structural characteristics of TYK2 JH2 resemble JAK2 JH2, but distinct stabilizing molecular interactions around helix alphaAL in the activation loop provide a structural basis for differences in substrate access and catalytic activities among JAK family JH2s. The structural and biochemical data suggest that ATP binding is functionally important for both TYK2 and JAK2 JH2s, whereas the regulatory phosphorylation appears to be a unique property of JAK2. Finally, the co-crystal structure of TYK2 JH2 complexed with a small molecule inhibitor demonstrates that JH2 is accessible to ATP-competitive compounds, which offers novel approaches for targeting cytokine signaling as well as potential therapeutic applications. PMID- 26359500 TI - Glyceraldehyde-3-phosphate Dehydrogenase Aggregates Accelerate Amyloid-beta Amyloidogenesis in Alzheimer Disease. AB - Alzheimer disease (AD) is a progressive neurodegenerative disorder characterized by loss of neurons and formation of pathological extracellular deposits induced by amyloid-beta peptide (Abeta). Numerous studies have established Abeta amyloidogenesis as a hallmark of AD pathogenesis, particularly with respect to mitochondrial dysfunction. We have previously shown that glycolytic glyceraldehyde-3-phosphate dehydrogenase (GAPDH) forms amyloid-like aggregates upon exposure to oxidative stress and that these aggregates contribute to neuronal cell death. Here, we report that GAPDH aggregates accelerate Abeta amyloidogenesis and subsequent neuronal cell death both in vitro and in vivo. Co incubation of Abeta40 with small amounts of GAPDH aggregates significantly enhanced Abeta40 amyloidogenesis, as assessed by in vitro thioflavin-T assays. Similarly, structural analyses using Congo red staining, circular dichroism, and atomic force microscopy revealed that GAPDH aggregates induced Abeta40 amyloidogenesis. In PC12 cells, GAPDH aggregates augmented Abeta40-induced cell death, concomitant with disruption of mitochondrial membrane potential. Furthermore, mice injected intracerebroventricularly with Abeta40 co-incubated with GAPDH aggregates exhibited Abeta40-induced pyramidal cell death and gliosis in the hippocampal CA3 region. These observations were accompanied by nuclear translocation of apoptosis-inducing factor and cytosolic release of cytochrome c from mitochondria. Finally, in the 3*Tg-AD mouse model of AD, GAPDH/Abeta co aggregation and mitochondrial dysfunction were consistently detected in an age dependent manner, and Abeta aggregate formation was attenuated by GAPDH siRNA treatment. Thus, this study suggests that GAPDH aggregates accelerate Abeta amyloidogenesis, subsequently leading to mitochondrial dysfunction and neuronal cell death in the pathogenesis of AD. PMID- 26359502 TI - Fish consumption and risk of depression: a meta-analysis. AB - BACKGROUND: The association between fish consumption and risk of depression is controversial. We performed a meta-analysis to evaluate the association. METHODS: A literature search was performed in PubMed, EMBASE and Web of Science database for all relevant studies up to March 2015. We pooled the relative risks (RRs) with 95% CIs from individual studies with random effects model, and conducted meta-regression to explore potential sources of heterogeneity. Publication bias was estimated by Egger's test and the funnel plot. RESULTS: A total of 26 studies involving 150,278 participants were included in the present meta-analysis. The pooled RR of depression for the highest versus lowest consumption of fish was 0.83 (95% CI 0.74 to 0.93). The findings remained significant in the cohort studies (RR=0.84, 95% CI 0.75 to 0.94, n=10) as well as in the cross-sectional studies (RR=0.82, 95% CI 0.68 to 1.00, n=16). When men and women were analysed separately, a significant inverse association was also observed. There was no evidence of publication bias. CONCLUSIONS: This meta-analysis indicates that high fish consumption can reduce the risk of depression. PMID- 26359501 TI - Deletion of MLIP (muscle-enriched A-type lamin-interacting protein) leads to cardiac hyperactivation of Akt/mammalian target of rapamycin (mTOR) and impaired cardiac adaptation. AB - Aging and diseases generally result from tissue inability to maintain homeostasis through adaptation. The adult heart is particularly vulnerable to disequilibrium in homeostasis because its regenerative abilities are limited. Here, we report that MLIP (muscle enriched A-type lamin-interacting protein), a unique protein of unknown function, is required for proper cardiac adaptation. Mlip(-/-) mice exhibited normal cardiac function despite myocardial metabolic abnormalities and cardiac-specific overactivation of Akt/mTOR pathways. Cardiac-specific MLIP overexpression led to an inhibition of Akt/mTOR, providing evidence of a direct impact of MLIP on these key signaling pathways. Mlip(-/-) hearts showed an impaired capacity to adapt to stress (isoproterenol-induced hypertrophy), likely because of deregulated Akt/mTOR activity. Genome-wide association studies showed a genetic association between Mlip and early response to cardiac stress, supporting the role of MLIP in cardiac adaptation. Together, these results revealed that MLIP is required for normal myocardial adaptation to stress through integrated regulation of the Akt/mTOR pathways. PMID- 26359503 TI - Maternal mental health, and child growth and development, in four low-income and middle-income countries. AB - OBJECTIVE: Extend analyses of maternal mental health and infant growth in low- and middle-income countries (LMICs) to children through age eight years, and broaden analyses to cognitive and psychosocial outcomes. DESIGN: Community-based longitudinal cohort study in four LMICs (Ethiopia, India, Peru and Vietnam). Surveys and anthropometric assessments were carried out when the children were approximately ages 1, 5 and 8 years. Risk of maternal common mental disorders (rCMDs) was assessed with the Self-Reporting Questionnaire (SRQ)-20 (score >=8). SETTING: Rural and urban as well as low- and middle-income communities. PARTICIPANTS: 7722 mothers and their children. MAIN OUTCOME MEASURES: Child stunting and underweight (Z score <=2 of height and weight for age), and <20th centile for: cognitive development (Peabody Picture Vocabulary Test), and the psychosocial outcomes self pride and life satisfaction. RESULTS: A high rate of rCMD, stunting and underweight was seen in the cohorts. After adjusting for confounders, significant associations were found between maternal rCMDs and growth variables in the first year of life, with persistence to age 8 years in India and Vietnam, but not in the other countries. India and Vietnam also showed significant associations between rCMDs and lower cognitive development. After adjustment, rCMD was associated with low life satisfaction in Ethiopia but not in the other cohorts. CONCLUSIONS: Associations of maternal rCMD in the first year of life with child outcomes varied across the study cohorts and, in some cases, persisted across the first 8 years of life of the child, and included growth, cognitive development and psychosocial domains. PMID- 26359504 TI - Respiratory and allergic health effects in a young population in proximity of a major industrial park in Oman. AB - BACKGROUND: Sohar industrial zone (SIZ), Oman, which started operating in 2006, contains many industries that potentially affect the health of the local population. This study's aim was to evaluate the health effects in a young population living near SIZ. METHODS: Patient visits to state health clinics for acute respiratory diseases (ARD), asthma, conjunctivitis and dermatitis were obtained for the period of 2006 to 2010, for children ages <20 years old, for two large provinces around SIZ. Three exposure zones were defined on the basis of the distance from SIZ determined as: <=5, >5 to 10, >=20 km to represent high, intermediate and control exposure zones, respectively. Age-specific and gender specific monthly counts of visits were modelled using generalised additive models controlling for time trends. The high and intermediate exposure zones were later combined together due to the similarity of associations. Exposure effect modification by age, gender and socioeconomic status (SES) was also tested. RESULTS: Living within 10 km from SIZ showed a greater association with ARD (risk ratio (RR)=2.5; 95% CI=2.3 to 2.7), asthma (RR=3.7; 95% CI=3.1 to 4.5), conjunctivitis (RR=3.1; 95% CI=2.9 to 3.5) and dermatitis (RR=2.7; 95% CI=2.5 to 3.0) when compared with the control zone. No differences in associations were found for gender and SES groups; greater effects were noticed in the <=14-year old group for asthma. CONCLUSIONS: This is the first study conducted in Oman to examine the health effects of a young population living near an industrial park. We hope that these findings will contribute in future developments of environmental health policies in Oman. PMID- 26359505 TI - School smoking policies and educational inequalities in smoking behaviour of adolescents aged 14-17 years in Europe. AB - BACKGROUND: Studies on the effects of school smoking policies are inconclusive and there is no research on whether the effects of school policies vary by educational level. We examined the association between school smoking policies and smoking behaviour among adolescents aged 14-17 years in Europe and assessed educational inequalities in these associations. METHODS: Data on 10,325 adolescents from 50 schools in six European cities were obtained from the 2013 SILNE survey. We measured student perceived policy, staff reported policy and its three subscales: regulations, communication and sanctions. The association between school policies and smoking outcomes (daily smoking and smoking on school premises) was adjusted for individual characteristics and for parental smoking. We tested interaction between school policies and educational level. RESULTS: Daily smoking was not associated with school smoking policies (eg, OR total policy=1.04, 95% CI 0.93 to 1.16 and OR student perceived policy=1.04, 95% CI 0.98 to 1.10). Smoking on school premises was less prevalent in schools with stronger staff reported total policy (OR=0.71, 95% CI 0.53 to 0.96). Other policy variables were also negatively associated with smoking on school premises, but not significantly (eg, OR student perceived policy=0.89, 95% CI 0.78 to 1.02). Associations between policy and smoking on school premises tended to be stronger in those with a low educational level, but none of the interactions tested were statistically significant. CONCLUSIONS: Our results suggest that school smoking policies may not have a direct effect on daily smoking but may reduce smoking on the school premises. We found no clear evidence for the effects of school policies to differ by educational level. PMID- 26359506 TI - Trends and socioeconomic disparities in preadolescent's health in the UK: evidence from two birth cohorts 32 years apart. AB - BACKGROUND: Compared to children and adults, little is known about changes in adolescent health over time. This study profiles the health of preadolescents in two distinct time periods, 1980 and 2012. METHODS: Secondary analysis of the British Cohort Study and the Millennium Cohort Study for preadolescents mostly aged between 10 and 11.5 years (range 9.75-13 years). The prevalence/average of, and socioeconomic gradients in, the following were compared between 1980 and 2012; general health problems, anthropometrics, allergic conditions, infectious diseases, health service use, smoking and parental smoking behaviour and maternal adiposity. Socioeconomic status was measured by familial income (3 groups). RESULTS: There were decreases in the proportion of hospital admissions (Delta= 0.10(-0.09:-0.11)) smoking (Delta=-0.12(-0.11:-0.13)), parental smoking (mother: (Delta=-0.19(-0.18:-0.21)) father: (Delta=-0.35(-0.34:-0.37), infectious diseases (measles: (Delta=-0.46(-0.45:-0.47)) whooping cough: (Delta=-0.07(-0.06:-0.07)) and hearing problems (Delta=-0.04(-0.03:-0.05)). There were no changes in limiting long-standing illness (Delta=0.00 (-0.00:0.00)), or the proportion of children having two or more accidents requiring medical attention (Delta=-0.02( 0.00:-0.02)). There were increases in the proportion overweight (Delta=0.18(0.17:0.19)), maternal overweight(Delta=0.22(0.21:0.23)) and obesity(Delta=0.12(0.11:0.13)), height for age(Delta=0.47(0.44:0.49)), weight for age (Delta=0.68(0.65:0.71)), proportion reporting chicken pox (Delta=0.28(0.27:0.29)), allergic conditions (eczema Delta=0.19(0.18:0.20)), asthma Delta=0.12(0.11:0.13), hay fever Delta=0.15(0.14:0.16)) and wearing glasses (Delta=0.08(0.07:0.09)). There were increases in socioeconomic gradients for limiting long-standing illness, smoking, overweight, weight for age, height for age, wearing glasses, asthma and the onset of puberty. CONCLUSIONS: There have been reductions in infectious diseases and tobacco exposure among British preadolescents, but overweight and allergic conditions have risen dramatically. Children from deprived families have benefitted least from improvements in health status, and have experienced the largest increases in health risks. PMID- 26359507 TI - Paediatric cardiac surgery in low-income and middle-income countries: a continuing challenge. AB - Despite advances in surgical and catheter-based treatment for congenital heart disease (CHD), there remain wide disparities across the globe. Ongoing international humanitarian and in-country programmes are working to address these issues with the ultimate goal to increase the quality and quantity of paediatric cardiac care, particularly in under-served regions of the world. This review aims to illustrate the reasons for these inequalities and suggests novel ways of improving access and sustainability of CHD programmes in low-income and middle income countries. PMID- 26359508 TI - Dietary calcium intake influences the relationship between serum 25 hydroxyvitamin D3 (25OHD) concentration and parathyroid hormone (PTH) concentration. AB - OBJECTIVES: To investigate whether dietary calcium intake will modify the relationship between serum 25-hydroxyvitamin D3 (25OHD) with intact serum parathyroid hormone (PTH) concentrations in apparently healthy Indian adolescents. STUDY DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: Apparently healthy adolescents aged 10-14 years (n=181), from Gujarat, western India. Study conducted from January 2012 to March 2014. METHODS: Serum 25OHD concentrations and intact serum PTH concentrations (both using chemiluminescent microparticle immunoassay) were measured. Diet was recorded through 24 h diet recall and calcium intake was computed (C-diet V.2.1). To assess relationship between 25OHD and PTH, data were dichotomised according to median calcium intakes (520 mg/day) and relationship between serum 25OHD and PTH in the two subgroups was plotted. RESULTS: Subjects with calcium intakes above median (>520 mg/day) had lower intact serum PTH values for given serum 25OHD concentration while those with calcium intakes below median (<520 mg/day) had higher intact serum PTH values for given serum 25OHD concentration. Serum 25OHD concentration was negatively correlated with intact serum PTH concentration at lower as well as higher calcium intakes (r=- 0.606 and -0.483, respectively, p<0.01 for both). Using a regression analysis, predicted values for intact serum PTH concentration for the given serum 25OHD concentrations were plotted. The plot revealed a negative shift with increasing calcium intake. CONCLUSIONS: Dietary calcium intake modifies the relationship between serum 25OHD concentrations and intact serum PTH concentrations. Thus, dietary calcium intake should be taken into account when assessing an individual's vitamin D status. PMID- 26359509 TI - Sleep Duration, Sleep Quality, and Markers of Subclinical Arterial Disease in Healthy Men and Women. AB - OBJECTIVE: Short and long sleep duration are associated with increased risk of clinical cardiovascular events, but the association between sleep duration and subclinical cardiovascular disease is not well established. We examined the association between sleep duration and sleep quality with coronary artery calcification (CAC) and with brachial-ankle pulse wave velocity (PWV) in a large sample of young and middle-aged asymptomatic adults. APPROACH AND RESULTS: We conducted a cross-sectional study of adult men and women who underwent a health checkup examination, including assessment of sleep duration and quality and coupled with either CAC (n=29 203) or brachial-ankle PWV (n=18 106). The multivariate-adjusted CAC score ratios (95% confidence interval) comparing sleep durations of <=5, 6, 8, and >=9 hours with 7 hours of sleep were 1.50 (1.17 1.93), 1.34 (1.10-1.63), 1.37 (0.99-1.89), and 1.72 (0.90-3.28), respectively (P for quadratic trend=0.002). The corresponding average differences in brachial ankle PWV were 6.7 (0.75-12.6), 2.9 (-1.7 to 7.4), 10.5 (4.5-16.5), and 9.6 (-0.7 to 19.8) cm/s, respectively (P for quadratic trend=0.019). Poor subjective sleep quality was associated with CAC in women but not in men, whereas the association between poor subjective sleep quality and brachial-ankle PWV was stronger in men than in women. CONCLUSIONS: In this large study of apparently healthy men and women, extreme sleep duration and poor subjective sleep quality were associated with increased prevalence of CAC and higher PWV. Our results underscore the importance of an adequate quantity and quality of sleep to maintain cardiovascular health. PMID- 26359510 TI - Ibrutinib Inhibits Platelet Integrin alphaIIbbeta3 Outside-In Signaling and Thrombus Stability But Not Adhesion to Collagen. AB - OBJECTIVE: Ibrutinib is an irreversible Bruton tyrosine kinase inhibitor approved for treatment of Waldenstrom macroglobulinemia, chronic lymphocytic leukemia, and mantle cell lymphoma that increases the risk of bleeding among patients. Platelets from ibrutinib-treated patients exhibit deficiencies in collagen-evoked signaling in suspension; however, the significance of this observation and how it relates to bleeding risk is unclear, as platelets encounter immobile collagen in vivo. We sought to clarify the effects of ibrutinib on platelet function to better understand the mechanism underlying bleeding risk. APPROACH AND RESULTS: By comparing signaling in suspension and during adhesion to immobilized ligands, we found that the collagen signaling deficiency caused by ibrutinib is milder during adhesion to immobilized collagen. We also found that platelets in whole blood treated with ibrutinib adhered to collagen under arterial shear but formed unstable thrombi, suggesting that the collagen signaling deficiency caused by ibrutinib may not be the predominant cause of bleeding in vivo. However, clot retraction and signaling evoked by platelet adhesion to immobilized fibrinogen were also inhibited by ibrutinib, indicating that integrin alphaIIbbeta3 outside in signaling is also effected in addition to GPVI signaling. When ibrutinib was combined with the P2Y12 inhibitor, cangrelor, thrombus formation under arterial shear was inhibited additively. CONCLUSIONS: These findings suggest that (1) ibrutinib causes GPVI and integrin alphaIIbbeta3 platelet signaling deficiencies that result in formation of unstable thrombi and may contribute toward bleeding observed in vivo and (2) combining ibrutinib with P2Y12 antagonists, which also inhibit thrombus stability, may have a detrimental effect on hemostasis. PMID- 26359511 TI - Purinergic Receptors in Thrombosis and Inflammation. AB - Under various pathological conditions, including thrombosis and inflammation, extracellular nucleotide levels may increase because of both active release and passive leakage from damaged or dying cells. Once in the extracellular compartment, nucleotides interact with plasma membrane receptors belonging to the P2 purinergic family, which are expressed by virtually all circulating blood cells and in most blood vessels. In this review, we focus on the specific role of the 3 platelet P2 receptors P2Y1, P2Y12, and P2X1 in hemostasis and arterial thrombosis. Beyond platelets, these 3 receptors, along with the P2Y2, P2Y6, and P2X7 receptors, constitute the main P2 receptors mediating the proinflammatory effects of nucleotides, which play important roles in various functions of circulating blood cells and cells of the vessel wall. Each of these P2 receptor subtypes specifically contributes to chronic or acute vascular inflammation and related diseases, such as atherosclerosis, restenosis, endotoxemia, and sepsis. The potential for therapeutic targeting of these P2 receptor subtypes is also discussed. PMID- 26359512 TI - Effect of High-Dose Statin Therapy on Drug-Eluting Stent Strut Coverage. AB - OBJECTIVE: The influence of high-dose statin therapy on the serial stent healing process has not been fully investigated. Using optical coherence tomography, the effect of high-dose statin therapy on stent strut coverage was evaluated in drug eluting stent-treated patients. APPROACH AND RESULTS: Sixty patients were randomly assigned to 2 groups according to the statin dose (atorvastatin 40 mg as high-dose statin therapy [n=29] versus pravastatin 20 mg as low-dose statin therapy [n=31]). Serial optical coherence tomographic evaluation post procedure and at the 3-month and 12-month follow-ups was performed in 50 patients with 54 stents (23 atorvastatin-treated patients versus 27 pravastatin-treated patients). The percentage of uncovered struts was defined as the ratio of uncovered struts/total struts. The primary end point was the percentage of uncovered struts at the 12-month follow-up. The secondary end point was the percentage of uncovered struts at the 3-month follow-up and the comparative percentage change (Delta) of uncovered struts at the 3- and 12-month follow-ups between the different dose statin therapies. The percentage of uncovered struts was 7.4% (range, 4.3%-10.4%) in atorvastatin-treated patients versus 10.6% (range, 5.7% 22.6%) in pravastatin-treated patients at the 3-month follow-up (P=0.13) and 1.3% (0.3%-3.8%) versus 2.5% (0.9%-9.7%), respectively, at the 12-month follow-up (P=0.01). The percentage Delta of uncovered struts from 3 to 12 months of follow up was -7.9+/-8.5% in atorvastatin-treated patients versus -9.3+/-12.5% in pravastatin-treated patients (P=0.67). CONCLUSIONS: This study suggested that high-dose statin therapy might provide a beneficial effect for the vascular healing process after drug-eluting stent implantation. PMID- 26359513 TI - Apolipoprotein A-I Limits the Negative Effect of Tumor Necrosis Factor on Lymphangiogenesis. AB - OBJECTIVE: Lymphatic endothelial dysfunction underlies the pathogenesis of many chronic inflammatory disorders. The proinflammatory cytokine tumor necrosis factor (TNF) is known for its role in disrupting the function of the lymphatic vasculature. This study investigates the ability of apolipoprotein (apo) A-I, the principal apolipoprotein of high-density lipoproteins, to preserve the normal function of lymphatic endothelial cells treated with TNF. APPROACH AND RESULTS: TNF decreased the ability of lymphatic endothelial cells to form tube-like structures. Preincubation of lymphatic endothelial cells with apoA-I attenuated the TNF-mediated inhibition of tube formation in a concentration-dependent manner. In addition, apoA-I reversed the TNF-mediated suppression of lymphatic endothelial cell migration and lymphatic outgrowth in thoracic duct rings. ApoA-I also abrogated the negative effect of TNF on lymphatic neovascularization in an ATP-binding cassette transporter A1-dependent manner. At the molecular level, this involved downregulation of TNF receptor-1 and the conservation of prospero related homeobox gene-1 expression, a master regulator of lymphangiogenesis. ApoA I also re-established the normal phenotype of the lymphatic network in the diaphragms of human TNF transgenic mice. CONCLUSIONS: ApoA-I restores the neovascularization capacity of the lymphatic system during TNF-mediated inflammation. This study provides a proof-of-concept that high-density lipoprotein-based therapeutic strategies may attenuate chronic inflammation via its action on lymphatic vasculature. PMID- 26359514 TI - (19)F NMR-, ESR-, and vis-NIR-spectroelectrochemical study of the unconventional reduction behaviour of a perfluoroalkylated fullerene: dimerization of the C70(CF3)10(-) radical anion. AB - The most abundant isomer of C70(CF3)10 (70-10-1) is a rare example of a perfluoroalkylated fullerene exhibiting electrochemically irreversible reduction. We show that electrochemical reversibility at the first reduction step is achieved at scan rates higher than 500 V s(-1). Applying ESR-, vis-NIR-, and (19)F NMR-spectroelectrochemistry, as well as mass spectrometry and DFT calculations, we show that the (70-10-1)(-) radical monoanion is in equilibrium with a singly-bonded diamagnetic dimeric dianion. This study is the first example of (19)F NMR spectroelectrochemistry, which promises to be an important method for the elucidation of redox mechanisms of fluoroorganic compounds. Additionally, we demonstrate the importance of combining different spectroelectrochemical methods and quantitative analysis of the transferred charge and spin numbers in the determination of the redox mechanism. PMID- 26359515 TI - Gold nanoparticle-catalyzed uranine reduction for signal amplification in fluorescent assays for melamine and aflatoxin B1. AB - A multifunctional fluorescence platform has been constructed based on gold nanoparticle (AuNP)-catalyzed uranine reduction. The catalytic reduction of uranine was conducted in aqueous solution using AuNPs as nanocatalyst and sodium borohydride as reducing reagent, which was monitored by fluorescence and UV-vis spectroscopy. The reaction rate was highly dependent on the concentration, size and dispersion state of AuNPs. When AuNPs aggregated, their catalytic ability decreased, and thereby a label-free fluorescent assay was developed for the detection of melamine, which can be used for melamine determination in milk. In addition, a fluorescent immunoassay for aflatoxin B1 (AFB1) was established using the catalytic reaction for signal amplification based on target-induced concentration change of AuNPs, where AFB1-BSA-coated magnetic beads and anti-AFB1 antibody-conjugated AuNPs were employed as capture and signal probe, respectively. The detection can be accomplished in 1 h and acceptable recoveries in spiked maize samples were achieved. The developed fluorescence system is simple, sensitive and specific, which could be used for the detection of a wide range of analytes. PMID- 26359516 TI - Triplex DNA logic gate based upon switching on/off their structure by Ag(+)/cysteine. AB - The formation of intramolecular triplex DNA can be regulated by Ag(+) and Cys (cysteine), which switch off/on the fluorescence of the oligonucleotides, 5' TAMRA-TTC TCT TCC TCT TCC TTC TGA CGA CAG TTG ACT CTT CCT TCT CCT TCT CTT-BHQ-2 3' (Oligo 1) and 3'-GAA GGA AGA GGA AGA GAA-5' (Oligo 2). Based on this principle, sensors for Ag(+) and Cys are developed. The sensor for Ag(+) has a linear range of 2.5 nM-40 nM and a detection limit of 1.8 nM, whereas the sensor for Cys has a linear range of 10.0 nM-120.0 nM and a detection limit of 8.2 nM. Furthermore, the fluorescence is reversible with the alternate addition of Ag(+) and Cys. We constructed a DNA logic gate using Ag(+) and Cys as the input, and the fluorescence intensity as the output. The DNA logic gate is simple; moreover, it has a fast response and good reversibility. PMID- 26359517 TI - Visual detection of mercury(II) based on recognition of the G-quadruplex conformational transition by a cyanine dye supramolecule. AB - A supramolecular probe for visual detection of mercury (Hg) has been designed by using a cyanine dye and AS1411 G-quadruplexes, which exhibits an obvious color change from red to blue in response to an increased level of Hg(2+). The supramolecular probe exhibits high selectivity and sensitivity towards Hg(2+) and is promising for the detection of environmental samples with the naked eye. PMID- 26359520 TI - Erratum. PMID- 26359519 TI - Stent-Retriever Thrombectomy for Stroke. PMID- 26359521 TI - Monkey-based Research on Human Disease: The Implications of Genetic Differences. PMID- 26359522 TI - Reply on Monkey-based Research on Human Disease: The Implications of Genetic Differences. PMID- 26359523 TI - Plants and bioenergy. PMID- 26359524 TI - Employee benefits: Plight of the postdoc. PMID- 26359525 TI - Authors' reply. PMID- 26359526 TI - Cardiac Causes of Syncope. They may faint and then feel fine, but the reason isn't always benign. PMID- 26359529 TI - Towards the clinical integration of an image-guided navigation system for percutaneous liver tumor ablation using freehand 2D ultrasound images. AB - Primary and metastatic liver tumors constitute a significant challenge for contemporary medicine. Several improvements are currently being developed and implemented to advance image navigation systems for percutaneous liver focal lesion ablation in clinical applications at the diagnosis, planning and intervention stages. First, the automatic generation of an anatomically accurate parametric model of the preoperative patient liver was proposed in addition to a method to visually evaluate and make manual corrections. Second, a marker was designed to facilitate rigid registration between the model of the preoperative patient liver and the patient during treatment. A specific approach was implemented and tested for rigid mapping by continuously tracking a set of uniquely identified markers and by accounting for breathing motion, facilitating the determination of the optimal breathing phase for needle insertion into the liver tissue. Third, to overcome the challenge of tracking the absolute position of the planned target point, an intra-operative ultrasound (US) system was integrated based on the Public Software Library for UltraSound and OpenIGTLink protocol, which tracks breathing motion in a 2D time sequence of US images. Additionally, to improve the visibility of liver focal lesions, an approach to determine spatio-temporal correspondence between the US sequence and the 4D computed tomography (CT) examination was developed, implemented and tested. This proposed method of processing anatomical model, rigid registration approach and the implemented US tracking and fusion method were tested in 20 anonymized CT and in 10 clinical cases, respectively. The presented methodology can be applied and used with any older 2D US systems, which are currently commonly used in clinical practice. PMID- 26359528 TI - Genetic variants associated with susceptibility to psychosis in late-onset Alzheimer's disease families. AB - Psychotic symptoms are frequent in late-onset Alzheimer's disease (LOAD) patients. Although the risk for psychosis in LOAD is genetically mediated, no genes have been identified. To identify loci potentially containing genetic variants associated with risk of psychosis in LOAD, a total of 263 families from the National Institute of Aging-LOAD cohort were classified into psychotic (LOAD+P, n = 215) and nonpsychotic (LOAD-P, n = 48) families based on the presence/absence of psychosis during the course of LOAD. The LOAD+P families yielded strong evidence of linkage on chromosome 19q13 (two-point [2-pt] logarithm of odds [LOD] = 3.8, rs2285513 and multipoint LOD = 2.7, rs541169). Joint linkage and association in 19q13 region detected strong association with rs2945988 (p = 8.7 * 10(-7)). Linkage results for the LOAD-P families yielded nonsignificant 19q13 LOD scores. Several 19q13 single-nucleotide polymorphisms generalized the association of LOAD+P in a Caribbean Hispanic (CH) cohort, and the strongest signal was rs10410711 (pmeta = 5.1 * 10(-5)). A variant located 24 kb upstream of rs10410711 and rs10421862 was strongly associated with LOAD+P (pmeta = 1.0 * 10(-5)) in a meta-analysis of the CH cohort and an additional non Hispanic Caucasian dataset. Identified variants rs2945988 and rs10421862 affect brain gene expression levels. Our results suggest that genetic variants in genes on 19q13, some of which are involved in brain development and neurodegeneration, may influence the susceptibility to psychosis in LOAD patients. PMID- 26359530 TI - Nucleotides in neuroregeneration and neuroprotection. AB - Brain injury generates the release of a multitude of factors including extracellular nucleotides, which exhibit bi-functional properties and contribute to both detrimental actions in the acute phase and also protective and reparative actions in the later recovery phase to allow neuroregeneration. A promising strategy toward restoration of neuronal function is based on activation of endogenous adult neural stem/progenitor cells. The implication of purinergic signaling in stem cell biology, including regulation of proliferation, differentiation, and cell death has become evident in the last decade. In this regard, current strategies of acute transplantation of ependymal stem/progenitor cells after spinal cord injury restore altered expression of P2X4 and P2X7 receptors and improve functional locomotor recovery. The expression of both receptors is transcriptionally regulated by Sp1 factor, which plays a key role in the startup of the transcription machinery to induce regeneration-associated genes expression. Finally, general signaling pathways triggered by nucleotide receptors in neuronal populations converge on several intracellular kinases, such as PI3K/Akt, GSK3 and ERK1,2, as well as the Nrf-2/heme oxigenase-1 axis, which specifically link them to neuroprotection. In this regard, regulation of dual specificity protein phosphatases can become novel mechanism of actions for nucleotide receptors that associate them to cell homeostasis regulation. This article is part of the Special Issue entitled 'Purines in Neurodegeneration and Neuroregeneration'. PMID- 26359527 TI - Idiosyncratic responding during movie-watching predicted by age differences in attentional control. AB - Much is known about how age affects the brain during tightly controlled, though largely contrived, experiments, but do these effects extrapolate to everyday life? Naturalistic stimuli, such as movies, closely mimic the real world and provide a window onto the brain's ability to respond in a timely and measured fashion to complex, everyday events. Young adults respond to these stimuli in a highly synchronized fashion, but it remains to be seen how age affects neural responsiveness during naturalistic viewing. To this end, we scanned a large (N = 218), population-based sample from the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) during movie-watching. Intersubject synchronization declined with age, such that older adults' response to the movie was more idiosyncratic. This decreased synchrony related to cognitive measures sensitive to attentional control. Our findings suggest that neural responsivity changes with age, which likely has important implications for real-world event comprehension and memory. PMID- 26359531 TI - Micropatterned charge heterogeneities via vapor deposition of aminosilanes. AB - Aminosilanes are routinely employed for charge reversal or to create coupling layers on oxide surfaces. We present a chemical vapor deposition method to pattern mica surfaces with regions of high-quality aminosilane (3 aminopropyltriethoxysilane, APTES) monolayers. The approach relies on the vapor deposition of an aminosilane through a patterned array of through-holes in a PDMS (poly(dimethylsiloxane)) membrane that acts as a mask. In aqueous solutions the surfaces have regular patterns of charge heterogeneities with minimal topographical variations over large areas. This versatile dry lift-off deposition method alleviates issues with multilayer formation and can be used to create charge patterns on curved surfaces. We identify the necessary steps to achieve high quality monolayers and charge reversal of the underlying mica surface: (1) hexane extraction to remove unreacted PDMS oligomers from the membrane that would otherwise deposit on and contaminate the substrate, (2) oxygen plasma treatment of the top of the membrane surfaces to generate a barrier layer that blocks APTES transport through the PDMS, and (3) low of the vapor pressure of APTES during deposition to minimize APTES condensation at the mica-membrane-vapor contact lines and to prevent multilayer formation. Under these conditions, AFM imaging shows that the monolayers have a height of 0.9 +/- 0.2 nm with an increase in height up to 3 nm at the mica-membrane-vapor contact lines. Fluorescence imaging demonstrates pattern fidelity on both flat and curved surfaces, for feature sizes that vary between 6.5 and 40 MUm. We verify charge reversal by measuring the double layer forces between a homogeneous (unpatterned) APTES monolayers and a mica surface in aqueous solution, and we characterize the surface potential of APTES monolayers by measuring the double-layer forces between identical APTES surfaces. We obtain a surface potential of +110 +/- 6 mV at pH 4.0. PMID- 26359532 TI - Overcoming the challenge of diagnosis of early HIV infection: a stepping stone to optimal patient management. AB - Prompt identification of individuals during the highly infectious acute or early stage of HIV infection has implications for both patient management and public health interventions. The studies on natural history of HIV infection over the last three decades have uncovered several clinical features and virological markers to diagnose early infection. However, the brevity of the acute symptomatic phase combined with the difficulty in identifying non-specific signs and symptoms poses diagnosis of early HIV infection as a remaining challenge. Furthermore, underestimation of risky behavior in the absence of detailed patient history and possible concurrent sexually transmitted infections render the diagnosis of recent infection difficult. Herein, we focus on the multifaceted clinical manifestations and the best usage of technological advancements to detect early HIV infection. Early diagnosis of HIV infection contributes to further improving patient outcomes and preventing transmission. PMID- 26359533 TI - Risk factors for lung infection in stroke patients: a meta-analysis of observational studies. AB - BACKGROUND: The aims of this meta-analysis were to evaluate the risk factors associated with lung infections in stroke patients and to provide evidence for prevention decisions. METHODS: We searched the Embase, PubMed, EBSCO and Web of Science databases to collect studies from January 2000 to July 2015. RESULTS: The meta-analysis identified 23 risk factors for lung infections in stroke patients, and the top 5, ranked by order according to odds ratio values (95% confidence interval), were as follows: multiple vertebrobasilar stroke, 22.99 (4.04, 130.83); National Institutes of Health Stroke Scale score >15 points, 14.63 (8.54, 25.08); mechanical ventilation, 10.20 (7.15, 14.57); nasogastric tube use, 9.87 (6.21, 15.70); and dysphagia, 7.50 (2.60, 21.65). CONCLUSION: Preventive measures should be taken against these risk factors to reduce the incidence of lung infection. PMID- 26359535 TI - Glycolipid biosurfactants: Potential related biomedical and biotechnological applications. AB - Glycolipids, consisting of a carbohydrate moiety linked to fatty acids, are microbial surface active compounds produced by various microorganisms. They are characterized by highly structural diversity and have the ability to decrease the surface and interfacial tension at the surface and interface respectively. Rhamnolipids, trehalolipids, mannosylerythritol-lipids and cellobiose lipids are among the most popular glycolipids. Moreover, their ability to form pores and destabilize biological membrane permits their use in biomedicine as antibacterial, antifungal and hemolytic agents. Their antiviral and antitumor effects enable their use in pharmaceutic as therapeutic agents. Also, glycolipids can inhibit the bioadhesion of pathogenic bacteria enabling their use as anti adhesive agents and for disruption of biofilm formation and can be used in cosmetic industry. Moreover, they have great potential application in industry as detergents, wetting agents and for flotation. Furthermore, glycolipids can act at the surface and can modulate enzyme activity permitting the enhancement or the inhibition of the activity of certain enzymes. PMID- 26359534 TI - Conditional ablation of p63 indicates that it is essential for embryonic development of the central nervous system. AB - p63 is a member of the p53 family that regulates the survival of neural precursors in the adult brain. However, the relative importance of p63 in the developing brain is still unclear, since embryonic p63(-/-) mice display no apparent deficits in neural development. Here, we have used a more definitive conditional knockout mouse approach to address this issue, crossing p63(fl/fl) mice to mice carrying a nestin-CreERT2 transgene that drives inducible recombination in neural precursors following tamoxifen treatment. Inducible ablation of p63 following tamoxifen treatment of mice on embryonic day 12 resulted in highly perturbed forebrain morphology including a thinner cortex and enlarged lateral ventricles 3 d later. While the normal cortical layers were still present following acute p63 ablation, cortical precursors and neurons were both reduced in number due to widespread cellular apoptosis. This apoptosis was cell-autonomous, since it also occurred when p63 was inducibly ablated in primary cultured cortical precursors. Finally, we demonstrate increased expression of the mRNA encoding another p53 family member, DeltaNp73, in cortical precursors of p63(-/-) but not tamoxifen-treated p63(fl/fl);R26YFP(fl/fl);nestin-CreERT2(+/O) embryos. Since DeltaNp73 promotes cell survival, then this compensatory increase likely explains the lack of an embryonic brain phenotype in p63(-/-) mice. Thus, p63 plays a key prosurvival role in the developing mammalian brain. PMID- 26359536 TI - Black Tea Consumption and Risk of Skin Cancer: An 11-Year Prospective Study. AB - Tea consumption has been shown to protect against skin carcinogenesis in laboratory-based studies; however, epidemiological evidence is limited and inconsistent. This prospective study examined the association between black tea consumption and the incidence of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Usual black tea consumption was estimated from food frequency questionnaires completed in 1992, 1994, and 1996 by 1,325 Australian adults. All histologically confirmed skin cancers diagnosed in participants from 1997 to 2007 were recorded. Relative risks (RRs) and 95% confidence intervals (CIs) were assessed using generalized linear models with Poisson and negative binomial distributions and adjusted for confounding factors including skin phenotype and sun exposure. Compared with never drinking black tea, drinking >=4 cups/day was not associated with BCC (RR = 1.03, 95% CI: 0.70-1.53; P-trend = 0.74) or SCC (RR = 1.25, 95% CI: 0.71-2.19; P-trend = 0.29) in person-based analyses. Stratification by previous history of skin cancer as well as tumor-based analyses also showed no significant associations between black tea intake and incidence of BCC or SCC tumors. Our results do not support the hypothesis that high black tea consumption reduces risk of skin cancer, including in people with a previous history of skin cancer. PMID- 26359537 TI - Multilayered silicene: the bottom-up approach for a weakly relaxed Si(111) with Dirac surface states. AB - Combining first principles investigations and scanning tunneling microscopy, we identify that the presumable van der Waals packed multilayered silicene sheets spontaneously transform into a diamond-structure bulk Si film due to strong interlayer couplings. In contrast to drastic surface reconstruction on conventional Si(111), multilayered silicene prepared by bottom-up epitaxy on Ag(111) exhibits a nearly ideal flat surface with only weak buckling. Without invoking Ag surfactants, ?3 *?3 honeycomb patterns emerge thanks to dynamic fluctuation of mirror-symmetric rhombic phases, similar to monolayered silicene [Chen et al., Phys. Rev. Lett., 2013, 110, 085504]. The weak relaxation enables novel surface states with a Dirac linear dispersion. PMID- 26359538 TI - Common Dorsal Stream Substrates for the Mapping of Surface Texture to Object Parts and Visual Spatial Processing. AB - Everyday objects are often composed of multiple parts, each with a unique surface texture. The neural substrates mediating the integration of surface features on different object parts are not fully understood, and potential contributions by both the ventral and dorsal visual pathways are possible. To explore these substrates, we collected fMRI data while human participants performed a difference detection task on two objects with textured parts. The objects could either differ in the assignment of the same texture to different object parts ("texture-location") or the types of texture ("texture-type"). In the ventral stream, comparable BOLD activation levels were observed in response to texture location and texture-type differences. In contrast, in a priori localized spatial processing regions of the dorsal stream, activation was greater for texture location than texture-type differences, and the magnitude of the activation correlated with behavioral performance. We confirmed the reliance of surface texture to object part mapping on spatial processing mechanisms in subsequent psychophysical experiments, in which participants detected a difference in the spatial distance of an object relative to a reference line. In this task, distracter objects occasionally appeared, which differed in either texture location or texture-type. Distracter texture-location differences slowed detection of spatial distance differences, but texture-type differences did not. More importantly, the distracter effects were only observed when texture-location differences were presented within whole shapes and not between separated shape parts at distinct spatial locations. We conclude that both the mapping of texture features to object parts and the representation of object spatial position are mediated by common neural substrates within the dorsal visual pathway. PMID- 26359539 TI - Immunohistochemistry staining for mismatch repair proteins: the endoscopic biopsy material provides useful and coherent results. AB - Immunohistochemistry (IHC) testing for mismatch repair proteins (MMRP) in patients with colorectal cancer can be performed on endoscopic biopsy material or the surgical resection material. Data are continuing to accumulate regarding the deleterious effect of neoadjuvant chemoradiation on MMRP expression. However, despite continuing rise in the use of endoscopic biopsies for IHC, most pathology departments still use mainly the surgical materials for IHC testing. In this study we compared the quality of stains among 96 colon cancer subjects with paired endoscopic and surgical material available for MLH1, MSH2, MSH6, and PMS2 stains (96 * 4, yielding 384 paired stains). Each slide received both a quantitative score (immunoreactivity [0-3] * percent positivity [0-4]) and a qualitative score (absent; weak and focal; strong). The quantitative scores of all MMRP were significantly higher among the endoscopic material (P<.001 for all). In 358 pairs (93.2%), both the endoscopic and operative material stained either strong (322, 83.9%) or absent (36, 9.4%). In 26 pairs (6.8%), the endoscopic material stained strong, whereas the operative material stained focal and weak. No endoscopic biopsy materials stained focal and weak. Our findings indicate that the biopsy material may provide more coherent results. Although these results may indicate that biopsy material provides coherent and useful results, it is yet to be determined if the demonstrated differences pose a real clinical problem in interpreting final results of IHC staining of such kind. Hence, we suggest that when available, the endoscopic material rather than the operative one should serve as the primary substrate for IHC staining. PMID- 26359540 TI - Androgen receptor, androgen-producing enzymes and their transcription factors in extramammary Paget disease. AB - Extramammary Paget disease (EMPD) has been known to frequently express androgen receptor (AR). Therefore, androgens could play roles in the biological behavior of Paget cells. 5alpha-Reductase (5alpha-red) types 1 and 2 and 17beta hydroxysteroid dehydrogenase type 5 (17beta-HSD5) are pivotal in situ regulators of androgen production in androgen-responsive tissues including androgen dependent neoplasms. Therefore, in this study, we immunolocalized AR, androgen producing enzymes, and their transcription factors to assess the state of in situ androgen production and actions and its correlation of invasiveness in EMPD. We studied 51 cases of EMPD with known clinicopathological status. AR, 5alpha-red1, 17beta-HSD5, and beta-catenin immunoreactivity was evaluated by using the modified H-score method while cyclin D1, p53, forkhead box protein P1, and a proliferation marker, Ki-67, were quantified using labeling index. The mean scores of AR, 5alpha-red1, and 17beta-HSD5 in invasive EMPD were all significantly higher than noninvasive EMPD (P < .0001). Ki-67 labeling index as well as the cyclin D1 score was also significantly higher in invasive than noninvasive lesions of EMPD. These results demonstrated that androgen receptor and androgen-producing enzymes were both associated with cell cycle regulation and subsequently the invasiveness of EMPD lesions and could also indicate those above as potential markers of invasive potentials in EMPD. PMID- 26359541 TI - Analysis of long-term mechanical grooming on large-scale test panels coated with an antifouling and a fouling-release coating. AB - Long-term grooming tests were conducted on two large-scale test panels, one coated with a fluorosilicone fouling-release (FR) coating, and one coated with a copper based ablative antifouling (AF) coating. Mechanical grooming was performed weekly or bi-weekly using a hand operated, electrically powered, rotating brush tool. The results indicate that weekly grooming was effective at removing loose or heavy biofilm settlement from both coatings, but could not prevent the permanent establishment of low-profile tenacious biofilms. Weekly grooming was very effective at preventing macrofouling establishment on the AF coating. The effectiveness of weekly grooming at preventing macrofouling establishment on the FR coating varied seasonally. The results suggest that frequent mechanical grooming is a viable method to reduce the fouling rating of ships' hulls with minimal impact to the coating. Frequent grooming could offer significant fuel savings while reducing hull cleaning frequencies and dry dock maintenance requirements. PMID- 26359542 TI - IL-33 alleviates DSS-induced chronic colitis in C57BL/6 mice colon lamina propria by suppressing Th17 cell response as well as Th1 cell response. AB - Interleukin (IL)-33, a member of the IL-1 cytokine family, is associated with autoimmune diseases including inflammatory bowel diseases (IBD). A few studies on animal models have shown that IL-33 can suppress Th1 cell response and improve Th2 cell response in mesenteric lymph nodes (MLN) and sera. However, there is little data published about the effect of IL-33 on Th17 cell in and Th1/Th2 cell in colon lamina propria. The aim of this study was to investigate the effect of IL-33 on Th17 cell in colon lamina propria of mice with dextran sulfate sodium (DSS) induced chronic colitis. We studied the influence of IL-33 on colonic tissue injury and clinical symptoms of colitis. The T cell subsets were measured by flow cytometry and the production of cytokines secreted by lamina propria lymphocytes (LPL) was measured by Enzyme-Linked Immunosorbent Assay (ELISA) and quantitative real-time PCR. We have found that rIL-33 treatment led to a significant alleviation of DSS induced chronic colitis as evidenced by 1) alleviation of weight loss, DAI, macroscopic changes and histological score; 2) down-regulating the rates and absolute cell numbers of Th17 and Th1 cell in LPL; 3) inducing secretion of lower levels of IFN-gamma and IL-17A. It is therefore concluded that IL-33 may play a therapeutic role in DSS-induced chronic colitis in mice by suppressing Th17 response and switching Th1 to Th2 response. PMID- 26359543 TI - Interleukin-6 enhances acid-induced apoptosis via upregulating acid-sensing ion channel 1a expression and function in rat articular chondrocytes. AB - The inflammatory cytokine interleukin-6 (IL-6) is a causative agent of rheumatoid arthritis (RA), a chronic inflammatory disease complicated with degenerative arthritic cartilage. However, the precise mechanism of IL-6 on chondrocyte apoptosis is largely unclear. Acid-sensing ion channels (ASICs), a family of extracellular H(+)-activated cation channels, can be transiently activated by extracellular acid and play a pivotal role in acid-induced cell injury. In the present study, to investigate the role of IL-6 in regulating acid-induced articular chondrocyte apoptosis, primary rat articular chondrocytes were subjected to different treatments with or without IL-6 in the presence of acid. The results showed that the mRNA and protein expressions of ASIC1a were significantly increased in articular cartilage and chondrocytes of adjuvant arthritis (AA) rats. IL-6 could dramatically upregulate the level of ASIC1a in a time- and dose-dependent manner, and induce the activation of JAK2, STAT3, ERK, JNK and NF-kappaB in articular chondrocytes. Moreover, both the respective inhibitors of these signaling pathways and the specific antibody against IL-6 receptor (tocilizumab) could partially abrogate the ASIC1a upregulation induced by IL-6. Furthermore, IL-6 inhibited the cell viability and enhanced LDH release, [Ca(2+)]i elevation, and apoptosis in acid-induced articular chondrocytes, and these changes could be reversed by using psalmotoxin 1(PcTX1), which is the specific antagonist of ASIC1a. In addition, pretreatment with PcTX1 could inhibit the downregulated expression of Bcl-2 and the upregulated expression of Bax induced by IL-6 in acid-induced articular chondrocytes. Taken together, these results indicated that IL-6 could enhance acid-induced articular chondrocyte apoptosis, the mechanism of which might partially be involved with its ability of regulating the activation of ASIC1a-dependent JAK2/STAT3 and MAPK/NF-kappaB signaling pathways. PMID- 26359544 TI - Effects of arsenic disulfide on proliferation, cytokine production, and frequencies of CD4(+), CD8(+), and regulatory T cells in mitogen-activated human peripheral blood mononuclear cells. AB - Influence of arsenic disulfide (As2S2) on human immune cells has little been investigated. Effects of As2S2 on proliferation, cytokine production, and frequencies of CD4(+) T, CD8(+) T and CD4(+)CD25(+)Foxp3(+) regulatory T cells in mitogen-activated human peripheral blood mononuclear cells were examined. Anti proliferative effects of As2S2 on peripheral blood mononuclear cells activated by T-cell mitogen were assessed by a colorimetric assay. Cytokine concentrations in the culture medium were measured with beads-array procedures followed by flow cytometry. CD4(+) T cells, CD8(+) T cells and CD4(+)CD25(+)Foxp3(+) regulatory T cells were stained with fluorescence-labeled specific antibodies followed by flow cytometry analysis. As2S2 at 1-10MUM significantly suppressed mitogen-activated proliferation of peripheral blood mononuclear cells (p<0.05). As2S2 at 10MUM inhibited production of IL-6, -10, -17A, tumor necrosis factor-alpha, and interferon-gamma from the activated peripheral blood mononuclear cells, though the effects were not statistically significant. As2S2 at 10MUM significantly suppressed the frequencies of CD4(+) T and CD8(+) T cells (p<0.05), whereas significantly enhanced the frequency of CD4(+)CD25(+)Foxp3(+) regulatory T cells (p<0.05). The data suggest that As2S2 attenuates T cell-mediated immunity by not only suppressing the proliferation of T cells and cytokine release but also increasing the frequency of regulatory T cells. T cell-mediated autoimmunity contributes to bone marrow failure in myelodysplastic syndrome (MDS), and thus the above As2S2 effects are beneficial for the treatment of MDS patients. PMID- 26359545 TI - Green tea epigallocatechin-3-gallate alleviates Porphyromonas gingivalis-induced periodontitis in mice. AB - Porphyromonas gingivalis causes inflammation, and leads to the periodontitis in gingival tissue damage and bone resorption. Epigallocatechin-3-gallate (EGCG) is a major polyphenol extract from green tea with plenty of pharmacological functions. The aim of this study was to determine whether continuous oral intake of EGCG would alleviate P. gingivalis-induced periodontitis. Eight-week BALB/c mice were administered with EGCG (0.02%) or vehicle in drinking water. They were fed normal food and orally infected with P. gingivalis every 2days, up to a total of 20 times, and then sacrificed at 15weeks of age. The P. gingivalis-challenged group markedly increased alveolar bone resorption of the maxillae in BALB/c mice by Micro-CT detection, and administration of EGCG resulted in a significant reduction in bone loss. Inflammation cytokine antibody array and enzyme linked immunosorbent assay revealed that some inflammatory mediators in serum were increased by P. gingivalis infection, but were lowered after EGCG treatment. High positive areas of IL-17 and IL-1beta in the gingival tissue were observed in the P. gingivalis-challenged mice, and were reduced by EGCG treatment. Real-time polymerase chain reaction (PCR) analyses also showed the expressions of IL-1beta, IL-6, IL-17, IL-23, TNF-alpha and other mediators in gingival tissue were higher in P. gingivalis-challenged mice, and were down-regulated with EGCG treatment, except IL-23. Our results suggest that EGCG, as a natural healthy substance, probably alleviates P. gingivalis-induced periodontitis by anti-inflammatory effect. PMID- 26359546 TI - Marginal fit and microbial leakage along the implant-abutment interface of fixed partial prostheses: An in vitro analysis using Checkerboard DNA-DNA hybridization. AB - STATEMENT OF PROBLEM: Bidirectional leakage through the implant-abutment interface still constitutes a major concern in implant-supported restorations. PURPOSE: The purpose of this in vitro study was to evaluate the marginal fit, before and after loading simulation, of 3-unit fixed partial prostheses supported by external hexagon or Morse cone implants and to identify and quantify up to 43 microbial species penetrating through the implant-abutment interface after loading. MATERIAL AND METHODS: Forty-eight dental implants with external hexagon (EH; n=24) or Morse cone (MC; n=24) connections were investigated. Experimental specimens were made from 2 implants restored with a 3-unit fixed partial prosthesis and divided into 2 groups (n=12) according to platform connection EH or MC. Vertical misfit at the implant-abutment interface was measured before and after loading (150 Ncm during 500,000 cycles at 1.8 Hz). checkerboard DNA-DNA hybridization was used to identify and quantify up to 38 bacterial and 5 Candida species colonizing the internal parts of the implants after loading. Generalized estimating equations were used for statistical analysis (alpha=.05). RESULTS: The mean values (mm, +/-SD) of vertical misfit for EH were 0.0131 +/-0.002 before loading and 0.0138 +/-0.002 after loading and for MC were 0.0132 +/-0.003 before loading and 0.0137 +/-0.001 after loading. Twenty-one bacterial species, including periodontal pathogens and C. albicans, were found colonizing the inner surfaces of EH implants after loading. None of the target species were detected in the internal parts of MC implants. CONCLUSIONS: EH implants showed higher microbial counts than MC implants, in which microbial colonization was not found after loading. Detected species included nonpathogens and microorganisms related to periodontal/periimplant diseases. Further studies are needed to evaluate the effect of loading simulation on the marginal misfit of 3-unit fixed partial prostheses supported by EH or MC implants, because no significant differences could be found either before or after loading. PMID- 26359547 TI - Suicide and Self-Harm by Drowning: A Review of the Literature. AB - The objectives of this study were to carry out a comprehensive review of the worldwide literature on suicidal behaviour by drowning. Systematic electronic searches of databases using various search terms were carried out. Recent trends in suicide and undetermined deaths due to drowning in England and Wales are described. The characteristics of patients presenting to the general hospital in Oxford, UK following attempted drowning are compared with self-poisoning patients. A total of 20 studies containing empirical data about suicide by drowning were identified, mainly concerning Western countries. Drowning suicides have declined in most countries in recent years. The proportion of undetermined deaths remains high. Drowning suicides and self-harm patients tend to be older, with only a small excess of males compared to those using other methods. This is an under-researched area that deserves good quality studies focusing upon prevention. PMID- 26359548 TI - Orthognathic surgery improves quality of life and depression, but not anxiety, and patients with higher preoperative depression scores improve less. AB - This study assessed quality of life (QoL), depression, and anxiety before and after orthognathic surgery and identified risk factors for poorer postoperative outcome. This multicentre prospective study included 140 patients from five French medical centres. We assessed patients before surgery (T1), 3 months after surgery (T2), and 12 months after surgery (T3). We assessed the severity of the orofacial deformity, physical, psychological, social, and environmental QoL (WHOQOL-BREF), and depression and anxiety (GHQ-28). Risk factors for poorer outcome were identified using linear mixed models. Between baseline and 12 months, there was significant improvement in psychological and social QoL and in depression (although below the norms reported in the general population), but not in anxiety. Physical QoL was poorer in patients who were younger, who had a mild orofacial deformity, and who were depressed. Psychological QoL was poorer in younger patients and in depressed patients. Social QoL was poorer in patients who were single, who had a mild orofacial deformity, and who were depressed. Although orthognathic surgery provides a moderate improvement in psychological and social QoL, the systematic screening and treatment of depression could further improve QoL after surgery because it is a major predictor of poor QoL in this population. PMID- 26359549 TI - Cyclic Peptides Incorporating Phosphotyrosine Mimetics as Potent and Specific Inhibitors of the Grb7 Breast Cancer Target. AB - The Grb7 adaptor protein is a therapeutic target for both TNBC and HER2+ breast cancer. A nonphosphorylated cyclic peptide 1 (known as G7-18NATE) inhibits Grb7 via targeting the Grb7-SH2 domain, but requires the presence of phosphate ions for both affinity and specificity. Here we report the discovery of malonate bound in the phosphotyrosine binding pocket of the apo-Grb7-SH2 structure. Based on this, we carried out the rational design and synthesis of two analogues of peptide 1 that incorporate carboxymethylphenylalanine (cmF) and carboxyphenylalanine (cF) as mimics of phosphotyrosine (pY). Binding studies using SPR confirmed that affinity for Grb7-SH2 domain is improved up to 9-fold over peptide 1 under physiological phosphate conditions (KD = 2.1-5.7 MUM) and that binding is specific for Grb7-SH2 over closely related domains (low or no detectable binding to Grb2-SH2 and Grb10-SH2). X-ray crystallographic structural analysis of the analogue bearing a cmF moiety in complex with Grb7-SH2 has identified the precise contacts conferred by the pY mimic that underpin this improved molecular interaction. Together this study identifies and characterizes the tightest specific inhibitor of Grb7 to date, representing a significant development toward a new Grb7-targeted therapeutic. PMID- 26359550 TI - The complete mitochondrial genome of speckled dace, Rhinichthys osculus. AB - In this study, we report the complete mitochondrial genome sequence of speckled dace, Rhinichthys osculus, for the first time. The length of this genome is 16 611 bp, and the mitochondrial genome harbors 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNA), two ribosomal RNA genes (rRNA), and one control region (D-loop), and it has a base composition of A (30.7%), G (16.3%), C (26.5%), and T (26.5%), indicating that the percentage of A + T (57.2%) was higher than that of G + C (42.8%). Most of the genes were located on the H-strand except for the ND6 gene and eight tRNA genes. The phylogenetic analysis showed that the R. osculus mitochondrial genome formed a cluster with the other seven Rhodeus genus genomes. The mitochondrial genome of R. osculus presented here will contribute to a better understanding of the population genetics. PMID- 26359551 TI - Antiviral role of grouper STING against iridovirus infection. AB - Stimulator of interferon genes (STING, also known as MITA, ERIS, MPYS or TMEM173) has been identified as a central component in the innate immune response to cytosolic DNA and RNA derived from different pathogens. However, the detailed role of STING during fish iridovirus infection still remained largely unknown. Here, the STING homolog from grouper Epinephelus coioides (EcSTING) was cloned and its effects on IFN response and antiviral activity were investigated. The full-length EcSTING cDNA was composed of 1590 bp and encoded a polypeptide of 409 amino acids with 80% identity to STING homolog from large yellow croaker. Amino acid alignment analysis indicated that EcSTING contained 4 predicated transmembrane motifs (TMs) in the N terminal, and a C-terminal domain (CTD) which consisted of a dimerization domain (DD), c-di-GMP-binding domain (CBD) and a C terminal tail (CTT). Expression profile analysis revealed that EcSTING was abundant in gill, spleen, brain, skin, and liver. Upon different stimuli in vivo, the EcSTING transcript was dramatically up-regulated after challenging with Singapore grouper iridovirus (SGIV), lipopolysaccharide (LPS) and polyinosin polycytidylic acid (poly I:C). Reporter gene assay showed that EcSTING activated ISRE, zebrafish type I IFN and type III IFN promoter in vitro. Mutant analysis showed that IFN promoter activity was mostly mediated by the phosphorylation sites at serine residue S379 and S387. Moreover, EcSTING induced type I and III IFN promoter activity could be impaired by overexpression of EcIRF3-DN or EcIRF7 DN, suggesting that EcSTING mediated IFN response in IRF3/IRF7 dependent manner. In addition, the cytopathic effect (CPE) progression of SGIV infection and viral protein synthesis was significantly inhibited by overexpression of EcSTING, and the inhibitory effect was abolished in serine residue S379 and S387 mutant transfected cells. Together, our results demonstrated that EcSTING might be an important regulator of grouper innate immune response against iridovirus infection. PMID- 26359552 TI - Effect of lysozyme solid-phase PEGylation on reaction kinetics and isoform distribution. AB - The combination of PEG-protein conjugation and chromatographic separation is generally known as solid-phase or on-column PEGylation and can provide advantages compared to commonly applied batch PEGylation. Even though the concept was already applied by several authors, changes in the isoform distribution compared to liquid-phase PEGylation due to sterically hindered PEGylation sites could not be confirmed. In this manuscript, a method for solid-phase PEGylation experiments in a 96-well plate format, using an automated liquid handling station is described. Applying size exclusion chromatography (SEC) and highly sensitive isoform analytics for mono-PEGylated lysozyme, we were able to investigate the differences in reaction kinetics and isoform distribution between adsorber-based PEGylation and modifications in free solution. Accordingly, solid-phase PEGylation with SP Sepharose FF and XL generally showed a reduced PEGylation reaction. In contrast to the predominant N-terminal PEGylation of lysozyme in liquid phase, a main modification of lys 97 and lys 116 was found for solid-phase experiments, which could be explained by binding orientations on corresponding adsorbent materials. Further experiments with varying amounts of bound protein additionally showed an influence on the isoform distribution of mono-PEGylated lysozyme. PMID- 26359553 TI - Are chemotherapy-associated symptoms underestimated? A view beyond common toxicity criteria. PMID- 26359554 TI - Changing a paradigm. PMID- 26359555 TI - Preventing readmissions with discharge education. PMID- 26359556 TI - A Case of Oral Metastasis From Hepatocellular Carcinoma Displayed on 18F-FDG PET/CT Imaging. AB - A 65-year-old man was diagnosed with hepatocellular carcinoma 4 years ago, for which he underwent interventional therapy and radiofrequency ablation after the right lobe partial hepatectomy. He was doing well, and an FDG PET/CT scan performed 1 year earlier did not reveal any hypermetabolic lesions. However, on recent examination, a soft tissue mass inside the oral cavity was found. 18F-FDG PET/CT imaging was performed to evaluate the possible metastasis. The images showed that the oral lesion was hypermetabolic. The pathology after biopsy confirmed oral metastasis from hepatocellular carcinoma. PMID- 26359557 TI - Gastric Carcinosarcoma and 18F-FDG PET/CT. AB - Gastric carcinosarcoma is a rare, malignant neoplasm that simultaneously comprises mixed epithelial and mesenchymal elements. In the present study, we report a case of gastric carcinosarcoma composed of rhabdomyosarcoma and adenocarcinoma on F-FDG PET/CT. PMID- 26359558 TI - Primary tracheal and bronchial lymphoma displayed on 18F-FDG PET/CT imaging. AB - A 46-year-old woman presented with cough for over 20 days, unrelieved by anti inflammation treatment. Diffuse wall thickening and mildly luminal stenosis of the lower trachea and both main bronchi were observed on chest CT examination. The pathology after bronchoscopy confirmed non-Hodgkin lymphoma (mucosa associated lymphatic tissue, MALT). FDG PET/CT was performed to evaluate the extent of the disease, which demonstrated the abnormal FDG accumulation in the diffusely thicken wall of trachea and bronchi, without lymph nodes and other extranodal tissue involvement. PMID- 26359559 TI - Vertebral Hemangiolymphangioma Mimics Bone Metastases on 99mTc-MDP SPECT/CT. AB - Hemangiolymphangioma is a very rare, congenital malformation of both lymphatic and blood vessels. In the present study, we report a case of vertebral hemangiolymphangioma that was misdiagnosed as bone metastasis on 99mTc-MDP SPECT/CT. PMID- 26359560 TI - The Prognostic Value of 18F-FDG Uptake Ratio Between the Right and Left Ventricles in Idiopathic Pulmonary Arterial Hypertension. AB - PURPOSE: Metabolic changes occur in the right ventricle (RV) under increased afterload in pulmonary arterial hypertension. FDG PET imaging has potential to assess RV function. In this study, we aimed to determine the prognostic value of metabolic changes of RV using FDG PET imaging in idiopathic pulmonary arterial hypertension (IPAH). PATIENTS AND METHODS: In this prospective investigation, patients newly diagnosed with IPAH were recruited. Patients underwent right heart catheterization, FDG PET imaging, and cardiac MR (CMR) within 1 week. Right ventricle hemodynamics, glucose metabolism derived from the FDG uptake levels, and functional parameters were obtained. The FDG uptake ratio between the RV and the left ventricle (LV) and its relation with the patients' survival were analyzed. RESULTS: A total of 45 IPAH patients were enrolled in this study, which included 13 male (28.9%) and 32 female (71.1%). The median follow-up time of this study was 1043 days. At the end of the follow-up, 36 patients survived, whereas 9 patients were deceased because of right heart failure. Multivariate Cox proportional hazard analysis showed that the ratio between the corrected RV and LV FDG uptake (cRV/LV) in both glucose-loading (cRV/LVg) and fasting (cRV/LVf) conditions independently predicted the mortality after adjusting for pulmonary vascular resistance index, mean right atrial pressure, and World Health Organization functional class. Kaplan-Meier survival analysis showed that patients with cRV/LVf greater than 143.65% in fasting condition (log rank, P = 0.030) or cRV/LVg greater than 120.55% in glucose-loading condition (log rank, P = 0.014) had worse prognosis. CONCLUSIONS: The FDG uptake ratio between the RV and LV can be an independent predictor for long-term prognosis of IPAH patients. PMID- 26359561 TI - Chest X-ray Artifact Caused by Bilateral 99mTc-Antimony Trisulfite Injection for Sentinel Node Imaging in a Patient With Breast Cancer. AB - A 52-year-old woman diagnosed with invasive ductal carcinoma of both breasts had a chest x-ray for preoperative assessment. A striking artifact was noted by the x ray technologist, who, as a result, became very concerned about radiation exposure from the patient. The patient had undergone bilateral sentinel lymph node injections in the nuclear medicine department with Tc-antimony trisulfite colloid just 2 hours before the chest x-ray. Radiation exposure to the x-ray technologist was determined to be similar to 8 hours of naturally occurring background radiation (~2.96 MUSv). PMID- 26359562 TI - Palliation of Extensive Metastatic Bone Disease With 223Ra-Dichloride alpha Particle Therapy in a Patient With Malignant Hereditary Paraganglioma Pheochromocytoma Syndrome With SDHB Mutation. AB - A 26-year-old woman with a 5-year history of metastatic paraganglioma due to hereditary paraganglioma-pheochromocytoma syndrome with SDHB mutation, who had failed multiple treatment regimens and had transfusion dependent pancytopenia, presented with progressive liver and bone metastases. She was unable to sleep due to painful skull metastases and had severe weakness in her extremities that limited her mobility and daily activities. She was treated with 2 doses of Ra dichloride (Xofigo, Ra) and had a dramatic improvement in pain control, mobility, and overall quality of life for 8 weeks, before passing away from pulmonary hemorrhage. PMID- 26359563 TI - Cardiac metastases of neuroendocrine tumors treated with 177Lu DOTATATE peptide receptor radionuclide therapy or 131I-MIBG therapy. AB - Neuroendocrine tumors have a propensity to metastasize to the heart, although the reason for this remains unknown. A review of 251 neuroendocrine tumor patients treated with Lu DOTATATE peptide receptor radionuclide therapy or I-MIBG therapy at our institution since 2003 revealed 2 patients with cardiac metastases (incidence, 0.8%), one treated with Lu DOTATATE and one with I-MIBG. We present the imaging findings of these 2 patients, as well as their management and responses to therapy. PMID- 26359564 TI - Resolution of Hyperreninemia, Secondary Hyperaldosteronism, and Hypokalemia With 177Lu-DOTATATE Induction and Maintenance Peptide Receptor Radionuclide Therapy in a Patient With Pancreatic Neuroendocrine Tumor. AB - A 54-year-old woman presented with a history of nausea, vomiting, diarrhea, and recurrent episodes of severe hypokalemia requiring hospitalization. Imaging revealed a pancreatic mass with liver metastases, histologically confirmed to be a neuroendocrine tumor. Elevated active renin and aldosterone levels were identified, and the patient was treated with 4 induction cycles of Lu-DOTATATE, which resolved the diarrhea, nausea, and hypokalemia, and normalized the renin and aldosterone levels. After 3 additional maintenance Lu-DOTATATE treatments, the pancreatic tumor had decreased in size, was deemed operable, and was resected. She remains on maintenance Lu-DOTATATE therapy with progression-free survival of 45 months thus far. PMID- 26359565 TI - Progressing Sclerosing Mesenteritis (Mesenteric Panniculitis) Mimics Progression of Malignancy After Neoadjuvant Chemotherapy for Gastric Adenocarcinoma on Serial 18F-FDG PET/CT. AB - A 62-year-old man was diagnosed with a moderately differentiated gastric adenocarcinoma in the proximal stomach. A staging 18F-FDG PET/CT showed an intensely FDG-avid gastric mass, as well as a mildly FDG-avid misty nodular mesentery. After 3 cycles of neoadjuvant chemotherapy, a follow-up PET/CT showed partial response of the gastric primary, with increase in the size of nodules in the mesentery and increased FDG uptake, raising concern of secondary malignancy. Biopsy of the mesentery revealed xanthogranulomatous inflammation, consistent with sclerosing mesenteritis. PMID- 26359566 TI - FDG PET brain scan demonstrated glucose hypometabolism of bilateral caudate nuclei and putamina in a patient with chorea-acanthocytosis. AB - Chorea-acanthocytosis is 1 type of neuroacanthocytosis that is a group of rare, hereditary neurodegenerative disorders. We presented a brain FDG PET finding of a 31-year-old woman with chorea-acanthocytosis. The images demonstrated significant hypometabolism in bilateral caudate nuclei and putamina. The finding of FDG PET is more prominent than that of MRI. Another interesting observation is the mildly increased FDG uptake in pituitary gland, although its relationship with the disease is unclear. PMID- 26359567 TI - Limbus Vertebra on Bone Scintigraphy in a Pediatric Patient. AB - Limbus vertebra involving the anterosuperior corner of a vertebral body is usually seen in adult patients, and it generally does not cause symptoms. An 8 year-old girl experienced lower back pain. Bone SPECT images revealed significantly increased tracer activity in the region of the anterior L4 vertebral body, which was shown on MRI to be a limbus vertebra. PMID- 26359568 TI - Combined Treatment With 131I-MIBG and Sunitinib Induces Remission in a Patient With Metastatic Paraganglioma Due to Hereditary Paraganglioma-Pheochromocytoma Syndrome From an SDHB Mutation. AB - A 22-year-old woman with rapidly progressing metastatic paraganglioma due to hereditary paraganglioma-pheochromocytoma syndrome from an SDHB mutation, who recurred after neoadjuvant chemotherapy, was found to be MIBG avid. She was treated with 2 I-MIBG treatments and concurrent sunitinib, achieving a complete response. She was in full remission for 9 months before developing bone metastases. PMID- 26359569 TI - Ectopic Corticotropin-Producing Neuroendocrine Tumor of the Pancreas Treated With 177Lu DOTATATE Induction and Maintenance Peptide Receptor Radionuclide Therapy. AB - A 57-year-old woman diagnosed with ectopic Cushing syndrome was found to have a 111In-octreotide-avid corticotropin-producing pancreatic neuroendocrine tumor with liver metastases. She was treated with 4 induction and 4 maintenance cycles of 177Lu-DOTATATE, which normalized her serum corticotropin levels and dramatically reduced the size of the pancreatic primary and liver metastases. PMID- 26359570 TI - 18F-FDG PET/CT Findings of Metastasis to Spongy Body of Penis From Urothelial Carcinoma of Bladder. AB - The spongy body of the penis metastasis from other primary sites is a rare clinical entity. It is frequently associated with widespread metastatic disease and poor prognosis clinically. We report a case of a 61-year-old man with a previous history of cystectomy due to infiltrating urothelial carcinoma of the bladder 12 months ago and presented with penile shaft swelling pain and hematuria for 3 months. The restaging F-FDG PET/CT scan demonstrated a hypermetabolic mass at his penile shaft. This lesion was confirmed on phallectomy to be infiltrating urothelial carcinoma metastasis from the known primary bladder tumor. PMID- 26359571 TI - FDG uptake in non-small cell lung cancer is not an independent predictor of EGFR or KRAS mutation status: a retrospective analysis of 206 patients. AB - PURPOSE: Data in the literature regarding the use of F-FDG avidity of non-small cell lung cancer (NSCLC) as an imaging biomarker to predict the status of epidermal growth factor receptor (EGFR) mutation are conflicting. Association between KRAS mutation and FDG avidity of NSCLC on PET/CT is not well known. We assessed whether the EGFR or KRAS mutation status in NSCLC can be predicted by FDG avidity by performing several different subgroup analyses to better compare with various published results. PATIENTS AND METHODS: After obtaining institutional review board approval, we enrolled patients (1) who had FDG PET/CT performed for staging of NSCLC, (2) with EGFR and KRAS mutational status of tumor identified, and (3) without uncontrolled diabetes. Univariate and multivariate regression analyses were performed to assess the relationship between the independent clinical variables (sex, age, smoking history, tumor histology, tumor size, stage, and SUV-derived variables) and the EGFR and KRAS mutation status. Separate analyses were performed for patients with adenocarcinomas. RESULTS: There were 206 patients (age, 33-88 years; 148 male/58 female; 71 ever smokers/135 never-smokers; 135 adenocarcinoma/71 squamous cell carcinoma; 22 stage I-II/184 stage III-IV; tumor size, 1.2-15.0 cm; SUVmax, 2.9-36.4; EGFR mutations present in 47; KRAS mutations present in 20). In multivariate analysis, sex, smoking history, histology, and tumor size were significantly associated with EGFR mutation but none of the SUV-derived variables was. Likewise, no correlation was found between the SUV-derived variables and KRAS mutation. CONCLUSIONS: Our results suggest that FDG avidity of NSCLC has no significant clinical value in predicting the EGFR or KRAS mutation status. PMID- 26359572 TI - Somatostatin receptor scintigraphy patterns in patients with sarcoidosis. AB - PURPOSE: Sarcoidosis is a multisystem granulomatous disorder, most frequently involving the lungs, skin, or eyes. Somatostatin receptor scintigraphy (SRS) can visualize sarcoid granulomas through binding of a radionuclide-coupled somatostatin analog to somatostatin receptors that are expressed in sarcoidosis. Uptake and patterns on SRS were studied and correlated to clinical and conventional findings. PATIENTS AND METHODS: Data of 218 SRSs undertaken for the analysis of potential sarcoidosis were studied. These scintigraphies were retrospectively studied on intensity uptake degrees and localization of sarcoidosis-associated lesions, and compared with conventional radiological techniques (chest x-ray and CT). RESULTS: In all but 1 of the 175 evaluable patients, SRS demonstrated uptake. In patients with thoracic sarcoidosis associated lesions, SRS improved the yield of visualization of chest x-ray in 20 (36%) and CT in 7 (32%) of histologically unproven patients, and in 31 (30%) and 8 (14%) of the histologically proven patients, respectively. Mediastinal lesions together with either eye, salivary glands, clavicular, or hilar localizations were most frequent demonstrated on SRS and constituted characteristic patterns. Exclusive extrapulmonary disease was found in 6% of the patients. CONCLUSIONS: Somatostatin receptor scintigraphy enhances the yield of investigations in sarcoidosis patients and therefore provides a useful and sensitive imaging technique to monitor organ involvement and therapeutic efficacy in patients with sarcoidosis. PMID- 26359574 TI - Sternal uptake of 99mTc-MAA in thoracic outlet syndrome. AB - Tc-macroaggregated albumin (MAA) uptake in the vertebrae has been reported in central vein occlusion, although its sternal uptake is rarely seen. We present a case in which Tc-MAA SPECT/CT showed spotty uptake in the sternum. Contrast enhanced CT revealed marked narrowing of the left subclavian vein at the thoracic outlet with a developed collateral vein running, in the left anterior chest subcutaneous tissue, between the sternum and left axilla. In this case, IV injection of Tc-MAA from the left forearm probably led to bone marrow uptake in the sternum due to retrograde venous flow through the collateral vein. PMID- 26359573 TI - Improved Diagnostic Accuracy of SPECT Through Statistical Analysis and the Detection of Hot Spots at the Primary Sensorimotor Area for the Diagnosis of Alzheimer Disease in a Community-Based Study: "The Osaki-Tajiri Project". AB - PURPOSE: SPECT is an important diagnostic tool for dementia. Recently, statistical analysis of SPECT has been commonly used for dementia research. In this study, we evaluated the accuracy of visual SPECT evaluation and/or statistical analysis for the diagnosis (Dx) of Alzheimer disease (AD) and other forms of dementia in our community-based study "The Osaki-Tajiri Project." PATIENTS AND METHODS: Eighty-nine consecutive outpatients with dementia were enrolled and underwent brain perfusion SPECT with 99mTc-ECD. Diagnostic accuracy of SPECT was tested using 3 methods: visual inspection (SPECT Dx), automated diagnostic tool using statistical analysis with easy Z-score imaging system (eZIS Dx), and visual inspection plus eZIS (integrated Dx). RESULTS: Integrated Dx showed the highest sensitivity, specificity, and accuracy, whereas eZIS was the second most accurate method. We also observed that a higher than expected rate of SPECT images indicated false-negative cases of AD. Among these, 50% showed hypofrontality and were diagnosed as frontotemporal lobar degeneration. These cases typically showed regional "hot spots" in the primary sensorimotor cortex (ie, a sensorimotor hot spot sign), which we determined were associated with AD rather than frontotemporal lobar degeneration. CONCLUSION: We concluded that the diagnostic abilities were improved by the integrated use of visual assessment and statistical analysis. In addition, the detection of a sensorimotor hot spot sign was useful to detect AD when hypofrontality is present and improved the ability to properly diagnose AD. PMID- 26359575 TI - Unexpected Pregnancy Revealed on 18F-NaF PET/CT. AB - A 48-year-old illiterate woman who is congenitally deaf and mute underwent 18F NaF PET/CT study to evaluate bone metastases from newly diagnosed breast cancer. Unexpectedly, a fetus in early second trimester was noted on CT images. In addition, subtle 18F-NaF uptake by the fetus could also be observed. PMID- 26359576 TI - FDG PET/CT in Early and Late Stages of SAPHO Syndrome: Two Case Reports With MRI and Bone Scintigraphy Correlation. AB - Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare disease, which may be underdiagnosed or misdiagnosed because of nonspecific clinical and imaging findings. We present 2 cases of SAPHO syndrome with MRI, bone scintigraphy, and FDG PET/CT findings. In case 1 with early-stage disease, the active osteitis showed osteolytic bone destruction with increased FDG uptake. In case 2 with late-stage disease, the inactive bone lesions presented as osteosclerosis with normal FDG uptake. Familiarity with the FDG PET/CT findings of SAPHO syndrome in different stages may be helpful for correct diagnosis. PMID- 26359577 TI - Practical Synthesis and Properties of 2,5-Diarylarsoles. AB - 2,5-Diarylarsoles were easily synthesized from nonvolatile arsenic precursors. Diiodoarsine was generated in situ and reacted with titanacyclopentadienes to give 2,5-diarylarsoles. The structures and optical properties were studied in comparison with those of 2,5-diarylphosphole. It was found that the arsoles were much more stable in the air than the phosphole. Single crystal X-ray diffraction revealed the arsenic atoms adopted a trigonal pyramidal structure, reflecting on the s-character of the lone pair. The obtained 2,5-diarylarsoles and 2,5 diarylphosphole showed intense emission in solutions and solid state. In addition, the optical properties were controlled by transition-metal coordination. PMID- 26359578 TI - A Theoretical Study of Ene Reactions in Solution: A Solution-Phase Translational Entropy Model. AB - Several density functional theory (DFT) methods, such as CAM-B3LYP, M06, omegaB97x, and omegaB97xD, are used to characterize a range of ene reactions. The Gibbs free energy, activation enthalpy, and entropy are calculated with both the gas- and solution-phase translational entropy; the results obtained from the solution-phase translational entropies are quite close to the experimental measurements, whereas the gas-phase translational entropies do not perform well. For ene reactions between the enophile propanedioic acid (2-oxo-1,3-dimethyl ester) and pi donors, the two-solvent-involved explicit+implicit model can be employed to obtain accurate activation entropies and free-energy barriers, because the interaction between the carbonyl oxygen atom and the solvent in the transition state is strengthened with the formation of C-C and O-H bonds. In contrast, an implicit solvent model is adequate to calculate activation entropies and free-energy barriers for the corresponding reactions of the enophile 4-phenyl 1,2,4-triazoline-3,5-dione. PMID- 26359579 TI - Erratum: Pashaj et al. Normal Doppler Reference Values of the Pericallosal Artery. Ultraschall in Med 2015; 36: 375-80. PMID- 26359580 TI - Continuous Versus Sequential Acquisition Head Computed Tomography: A Phantom and Clinical Image Quality Comparative Study. AB - OBJECTIVE: Sequential computed tomography (CT) technique remains the most common protocol for CT evaluation of the head despite nearly universal adoption of continuous technique for all other body parts. This may be attributable to the belief by radiologists that this technique is superior to helical scanning uniquely for this indication. This study attempts to clarify the issue. METHODS: A phantom evaluation and a prospective randomized clinical image quality trial were performed comparing sequential and helical technique using the most current generation 128-row detector CT scanner. RESULTS: Phantom evaluation demonstrated equivalence between the 2 techniques for low-contrast resolution and line pair spatial discrimination. Continuous scanning provided the highest contrast-to noise ratio. There was no significant difference between the 2 techniques regarding image quality except for cortical visualization at the cerebral hemispheres, which was subtly but significantly superior for sequential technique. CONCLUSIONS: Head CT image quality for sequential and continuous techniques are virtually equivalent. PMID- 26359582 TI - Quantitative Evaluation of Noncontrast Computed Tomography of the Head for Assessment of Anemia. AB - BACKGROUND AND PURPOSE: Anemia is an underdiagnosed clinical entity with significant mortality and morbidity. We aimed to assess whether attenuation of dural venous sinuses correlates with hemoglobin/hematocrit and to determine if the degree of anemia can be predicted by quantitative analysis of unenhanced computed tomography (CT) of the head. MATERIALS AND METHODS: This is an institutional review board-approved retrospective study including 500 patients who underwent emergency department investigation for potential central nervous system etiology of their symptoms with unenhanced CT head at a tertiary care center. Computed tomographic attenuation values were obtained by 2 independent readers, whereas 2 separate investigators collected clinical data. Regression analyses were performed to evaluate the strength of correlation and the predictability of anemia and its severity on unenhanced CT. Receiver operating characteristic curve analyses were performed to evaluate sensitivity, specificity, as well as positive and negative predictive values. RESULTS: A total of 243 met the inclusion criteria, and attenuation values for all the dural venous sinuses were averaged and categorized according to hemoglobin values of less than 8, 8 to 10, 10 to 14, and greater than 14. Mean CT attenuation values for both readers were 36.30, 42.35, 47.99, and 53.25 Hounsfield units. Regression analysis revealed the highest positive correlation of hemoglobin/hematocrit with attenuation at the confluence of sinuses with R value of 0.63 and 0.60. The sensitivity, specificity, and negative predictive value of detecting hemoglobin of less than 10 at confluence of sinuses were 91.2%, 88.5%, and 98.6%, respectively. Interobserver agreement was found to be good (0.64) using the kappa statistic. CONCLUSIONS: Our study substantiates direct positive correlation between CT attenuation of dural venous sinuses and hemoglobin/hematocrit, with strongest correlation at the confluence of sinuses with good sensitivity, specificity, and negative predictive value. PMID- 26359581 TI - High-Resolution Qualitative and Quantitative Magnetic Resonance Evaluation of the Glenoid Labrum. AB - OBJECTIVE: This study aimed to implement qualitative and quantitative magnetic resonance sequences for the evaluation of labral pathology. METHODS: Six glenoid labra were dissected, and the anterior and posterior portions were divided into normal, mildly degenerated, or severely degenerated groups using gross and magnetic resonance findings. Qualitative evaluation was performed using T1 weighted, proton density-weighted, spoiled gradient echo and ultrashort echo time (UTE) sequences. Quantitative evaluation included T2 and T1rho measurements as well as T1, T2*, and T1rho measurements acquired with UTE techniques. RESULTS: Spoiled gradient echo and UTE sequences best demonstrated labral fiber structure. Degenerated labra had a tendency toward decreased T1 values, increased T2/T2* values, and increased T1rho values. T2* values obtained with the UTE sequence allowed for delineation among normal, mildly degenerated, and severely degenerated groups (P < 0.001). CONCLUSIONS: Quantitative T2* measurements acquired with the UTE technique are useful for distinguishing among normal, mildly degenerated, and severely degenerated labra. PMID- 26359583 TI - Differential Chest Computed Tomography Findings of Pulmonary Parasite Infestation Between the Paragonimiasis and Nonparagonimiatic Parasite Infestation. AB - OBJECTIVE: The aims of this study were to evaluate the chest computed tomography findings of parasite infestation regardless of pathogen and to compare the differential findings between paragonimiasis and nonparagonimiatic parasite infestation (NPPI). METHODS: Between January 2008 and November 2011, 75 patients (46 men; 52.9 +/- 14.1 years) with serologically proven parasite infestation and available chest computed tomography images were evaluated. Computed tomography images of 40 patients with paragonimiasis and 35 patients with NPPI (13 with sparganosis, 12 with toxocariasis, 8 with cysticercosis, and 2 with clonorchiasis) were assessed for the presence or absence of pleural abnormalities, consolidation, cavitary lesions, aggregated cysts, worm-migration tracts, and pure ground-glass opacity. Findings associated with consolidation were further assessed for characteristics including size, perilesional ground glass opacity, presence of perilesional centrilobular nodules, and internal low attenuation, and multisegmentality and bilaterality were assessed for all patients. RESULTS: In both groups, the most common pleural abnormality was pleural effusion (42.5% in paragonimiasis vs 22.9% in NPPI, P = 0.09), and the most common pulmonary abnormality was consolidation (82.5% vs 80.0%, P = 1.00). Multisegmentality (35% vs 42.9%, P = 0.64) and bilaterality (55.0% vs 60%, P = 0.82) of pleuropulmonary lesions were often observed in both groups. Internal low attenuation, perilesional centrilobular nodules, cavitary lesions, and worm migration tracts were more frequently found in the paragonimiasis group (P <= 0.05). CONCLUSIONS: The presence of internal low attenuation and perilesional centrilobular nodules associated with pulmonary consolidative lesions, along with cavitary lesions and worm-migration tracts, is more frequent in patients with paragonimiasis than in patients with NPPI. PMID- 26359584 TI - Dynamic Susceptibility Contrast Perfusion-Weighted Magnetic Resonance Imaging and Diffusion-Weighted Magnetic Resonance Imaging in Differentiating Recurrent Head and Neck Cancer From Postradiation Changes. AB - PURPOSE: The aim of this study was to assess dynamic susceptibility contrast (DSC) perfusion-weighted magnetic resonance (MR) imaging and diffusion-weighted MR imaging in differentiating recurrent head and neck cancer from postradiation changes. METHODS: A prospective study was done on 41 patients with head and neck cancer after radiotherapy who underwent diffusion-weighted MR imaging, DSC perfusion-weighted MR imaging, and routine postcontrast MR imaging. The apparent diffusion coefficient (ADC) map and time signal intensity curve of the lesion were created. The ADC value, DSC percentage (DSC%), and contrast enhancement percentage of the lesion were calculated. The final diagnosis was done with biopsy. RESULTS: There was significant difference (P = 0.001) in ADC between recurrent cancer (0.94 +/- 0.16 * 10mm/s) and postradiation changes (1.37 +/- 0.12 * 10mm/s). There was significant difference (P = 0.001) in DSC% of recurrent cancer (30.9% +/- 5.16%) and postradiation changes (12.1% +/- 3.06%). Selection of ADC equal to or less than 1.07 * 10mm/s and DSC% greater than 16.6% to predict recurrence have areas under the curve of 0.822 and 0.900 and accuracy of 92.7% and 95.1%, respectively. Combination of ADC and DSC% has are under the curve of 0.992 and accuracy of 97.6%. CONCLUSIONS: Combined ADC and DSC% are noninvasive imaging parameters that can play a role in the differentiation of recurrent head and neck cancer from postradiation changes. PMID- 26359585 TI - Magnetic Resonance Imaging Features of Schwannoma of the Sinonasal Tract. AB - PURPOSE: The purpose of the study was to explore the characteristic magnetic resonance imaging (MRI) findings of schwannoma of the sinonasal tract. METHODS: Eighteen patients with histopathologically confirmed sinonasal schwannoma underwent conventional MRI, and 12 had dynamic contrast-enhanced MRI studies synchronously. The morphology feature, signal intensity, enhancement degree, and time intensity curve (TIC) pattern of schwannomas were retrospectively analyzed. RESULTS: This entity appeared as a well-circumscribed, oval or fusiform soft tissue mass with a mean greatest diameter of 38 mm. Schwannomas exhibited isointense on T1-weighted image in 12 patients and hypointense in 6. On T2 weighted image, the lesions were heterogeneously isointense in 14 patients and hyperintense in 4. The lesions had heterogeneously moderate and marked contrast enhancement in 2 and 16, respectively. The mottled-, island-, and multicyst-like appearance were identified in 3, 4, and 11, respectively. Compared with inverted papilloma and lobular capillary hemangioma, the type I TIC is characteristic of schwannoma. CONCLUSIONS: A well-circumscribed mass displaying T2 intermediate signal intensity, marked enhancement, and type I TIC, with cystic changes, strongly suggests the diagnosis of sinonasal schwannoma. PMID- 26359586 TI - Green synthesis of fluorescence carbon nanoparticles from yum and application in sensitive and selective detection of ATP. AB - Fluorescent carbon nanoparticles (CPs), a fascinating class of recently discovered nanocarbons, have been widely known as some of the most promising sensing probes in biological or chemical analysis. In this study, we demonstrate a green synthetic methodology for generating water-soluble CPs with a quantum yield of approximately 24% via a simple heating process using yum mucilage as a carbon source. The prepared carbon nanoparticles with an ~10 nm size possessed excellent fluorescence properties, and the fluorescence of the CPs was strongly quenched by Fe(3+), and recovered by adenosine triphosphate (ATP), thus, an 'off' and 'on' system can be easily established. This 'CPs-Fe(3+)-ATP' strategy was sensitive and selective at detecting ATP with the linear range of 0.5 umol L(-1) to 50 umol L(-1) and with a detection limit of 0.48 umol L(-1). PMID- 26359587 TI - Do financial incentives trump clinical guidance? Hip Replacement in England and Scotland. AB - Following devolution in 1999 England and Scotland's National Health Services diverged, resulting in major differences in hospital payment. England introduced a case payment mechanism from 2003/4, while Scotland continued to pay through global budgets. We investigate the impact this change had on activity for Hip Replacement. We examine the financial reimbursement attached to uncemented Hip Replacement in England, which has been more generous than for its cemented counterpart, although clinical guidance from the National Institute for Clinical Excellence recommends the later. In Scotland this financial differential does not exist. We use a difference-in-difference estimator, using Scotland as a control, to test whether the change in reimbursement across the two countries had an influence on treatment. Our results indicate that financial incentives are directly linked to the faster uptake of the more expensive, uncemented Hip Replacement in England, which ran against the clinical guidance. PMID- 26359588 TI - Physicochemical properties and adsorption of cholesterol by okra (Abelmoschus esculentus) powder. AB - Okra (Abelmoschus esculentus) is a widely used medicine and functional food. In order to clarify the effects of the particle size on its functional properties, okra pods were subjected to superfine grinding, and its properties were determined using different methods. Four particle size levels of okra powders were prepared: 380 to 250, 250 to 75, 75 to 40 and less than 40 MUm. The results showed that superfine grinding technology could efficiently pulverize the particles into the submicron scale, whose distribution was close to a Gaussian distribution. With decreasing okra powder size, the specific surface area, water holding capacity (WHC), water-retention capacity (WRC), oil-binding capacity (OBC), tapped density and total flavonoids extraction were increased significantly (p < 0.05). Moreover, the adsorption of cholesterol by okra powder was improved after superfine grinding. These results suggest that okra powder can be used in food manufacturing as a functional food ingredient. PMID- 26359589 TI - The Effectiveness and Risks of Fluoroscopically-Guided Cervical Medial Branch Thermal Radiofrequency Neurotomy: A Systematic Review with Comprehensive Analysis of the Published Data. AB - OBJECTIVE: To determine the effectiveness and risks of fluoroscopically-guided cervical medial branch thermal radiofrequency neurotomy (CMBTRFN) for treating chronic neck pain of zygapophysial joint origin. DESIGN: Systematic review of the literature with comprehensive analysis of the published data. INTERVENTIONS: Four reviewers formally trained in evidence-based medicine searched the literature on CMBTRFN. Each assessed the methodologies of studies found and appraised the quality of evidence presented. OUTCOME MEASURES: The primary outcomes assessed were 100% relief of pain 6 and 12 months after treatment. Other outcomes were noted if reported. The evidence was evaluated in accordance with the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) system. RESULTS: The searches yielded eight primary publications on the effectiveness of the procedure. The evidence shows a majority of patients were pain free at 6 months and over a third were pain free at 1 year. The number needed to treat for complete pain relief at 6 months is 2. The evidence of effectiveness is of high quality according to the GRADE system. Twelve papers were found reporting unwanted effects, most of which are minor and temporary. No serious complications have ever been reported from procedures performed according to the published guidelines. The evidence of risks is of low quality according to the GRADE system. CONCLUSIONS: If performed as described in the International Spine Intervention Society Guidelines, fluoroscopically-guided CMBTRFN is effective for abolishing zygapophysial joint pain and carries only minor risks. PMID- 26359591 TI - Outside in: from observation to aetiology. PMID- 26359590 TI - In Situ Lipolysis and Synchrotron Small-Angle X-ray Scattering for the Direct Determination of the Precipitation and Solid-State Form of a Poorly Water-Soluble Drug During Digestion of a Lipid-Based Formulation. AB - In situ lipolysis and synchrotron small-angle X-ray scattering (SAXS) were used to directly detect and elucidate the solid-state form of precipitated fenofibrate from the digestion of a model lipid-based formulation (LBF). This method was developed in light of recent findings that indicate variability in solid-state form upon the precipitation of some drugs during the digestion of LBFs, addressing the need to establish a real-time technique that enables solid-state analysis during in vitro digestion. In addition, an ex situ method was also used to analyse the pellet phase formed during an in vitro lipolysis experiment at various time points for the presence of crystalline drug. Fenofibrate was shown to precipitate in its thermodynamically stable crystalline form upon digestion of the medium-chain LBF, and an increase in scattering intensity over time corresponded well to an increase in concentration of precipitated fenofibrate quantified from the pellet phase using high-performance liquid chromatography. Crossed polarized light microscopy served as a secondary technique confirming the crystallinity of the precipitated fenofibrate. Future application of in situ lipolysis and SAXS may focus on drugs, and experimental conditions, which are anticipated to produce altered solid-state forms upon the precipitation of drug (i.e., polymorphs, amorphous forms, and salts). PMID- 26359592 TI - Specialised assertive intervention in early psychosis. PMID- 26359593 TI - Investment in mental health: a battle for resources. PMID- 26359594 TI - Suicidal behaviour: identifying the best preventive interventions. PMID- 26359595 TI - Elucidating postpartum depression through statistics. PMID- 26359596 TI - Broken promises: indigenous peoples' mental health in South America. PMID- 26359597 TI - Turn on and tune in to evidence-based psychedelic research. PMID- 26359598 TI - Health equity and mental health in post-2015 sustainable development goals. PMID- 26359599 TI - Reification of the paediatric bipolar hypothesis in the USA. PMID- 26359601 TI - Corrections. PMID- 26359603 TI - Wales aims to turn round unhappy Valleys. PMID- 26359604 TI - Depression: an economic and moral case to tackle the crisis. PMID- 26359605 TI - Highlights from the 9th International Early Psychosis Conference, Tokyo, Japan. PMID- 26359606 TI - Mary Robertson: unravelling Tourette's syndrome. PMID- 26359607 TI - The wood for the trees. PMID- 26359608 TI - Screening psychiatrists: the good, the bad, and the dippy. PMID- 26359609 TI - In my mind's eye. PMID- 26359610 TI - Intensive case management for high-risk patients with first-episode psychosis: service model and outcomes. AB - BACKGROUND: The first episode of psychosis is a crucial period when early intervention can alter the trajectory of the young person's ongoing mental health and general functioning. After an investigation into completed suicides in the Early Psychosis Prevention and Intervention Centre (EPPIC) programme, the intensive case management subprogramme was developed in 2003 to provide assertive outreach to young people having a first episode of psychosis who are at high risk owing to risk to self or others, disengagement, or suboptimal recovery. We report intensive case management model development, characterise the target cohort, and report on outcomes compared with EPPIC treatment as usual. METHODS: Inclusion criteria, staff support, referral pathways, clinical review processes, models of engagement and care, and risk management protocols are described. We compared 120 consecutive referrals with 50 EPPIC treatment as usual patients (age 15-24 years) in a naturalistic stratified quasi-experimental real-world design. Key performance indicators of service use plus engagement and suicide attempts were compared between EPPIC treatment as usual and intensive case management, and psychosocial and clinical measures were compared between intensive case management referral and discharge. FINDINGS: Referrals were predominately unemployed males with low levels of functioning and educational attainment. They were characterised by a family history of mental illness, migration and early separation, with substantial trauma, history of violence, and forensic attention. Intensive case management improved psychopathology and psychosocial outcomes in high-risk patients and reduced risk ratings, admissions, bed days, and crisis contacts. INTERPRETATION: Characterisation of intensive case management patients validated the clinical research focus and identified a first episode of psychosis high-risk subgroup. In a real-world study, implementation of an intensive case management stream within a well-established first episode of psychosis service showed significant improvement in key service outcomes. Further analysis is needed to determine cost savings and effects on psychosocial outcomes. Targeting intensive case management services to high-risk patients with unmet needs should reduce the distress associated with pathways to care for patients, their families, and the community. FUNDING: National Health & Medical Research Council and the Colonial Foundation. PMID- 26359611 TI - Clinical effectiveness of a staff training intervention in mental health inpatient rehabilitation units designed to increase patients' engagement in activities (the Rehabilitation Effectiveness for Activities for Life [REAL] study): single-blind, cluster-randomised controlled trial. AB - BACKGROUND: Mental health inpatient rehabilitation services focus on people with complex psychosis who have, for example, treatment-refractory symptoms, cognitive impairment, and severe negative symptoms, which impair functioning and require lengthy admission. Engagement in activities could lead to improvement in negative symptoms and function, but few trials have been done. We aimed to investigate the effectiveness of a staff training intervention to increase patients' engagement in activities. METHODS: We did a single-blind, two-arm, cluster-randomised controlled trial in 40 mental health inpatient rehabilitation units across England. Units were randomly allocated to either a manual-based staff training programme delivered by a small intervention team (intervention group, n=20) or standard care (control group, n=20). The primary outcome was patients' engagement in activities 12 months after randomisation, measured with the time use diary. With this measure, both the degree of engagement in an activity and its complexity are recorded four times a day for a week, rated on a scale of 0-4 for every period (maximum score of 112). Analysis was by intention-to-treat. Random effects models were used to compare outcomes between study groups. Cost effectiveness was assessed by combining service costs with the primary outcome. This study is registered with Current Controlled Trials (ISRCTN25898179). FINDINGS: Patients' engagement in activities did not differ between study groups (coefficient 1.44, 95% CI -1.35 to 4.24). An extra L101 was needed to achieve a 1% increase in patients' engagement in activities with the study intervention. INTERPRETATION: Our training intervention did not increase patients' engagement in activities after 12 months of follow-up. This failure could be attributable to inadequate implementation of the intervention, a high turnover of patients in the intervention units, competing priorities on staff time, high levels of patients' morbidity, and ceiling effects because of the high quality of standard care delivered. Further studies are needed to identify interventions that can improve outcomes for people with severe and complex psychosis. FUNDING: National Institute for Health Research. PMID- 26359612 TI - Short-term and long-term effects of psychosocial therapy for people after deliberate self-harm: a register-based, nationwide multicentre study using propensity score matching. AB - BACKGROUND: Although deliberate self-harm is a strong predictor of suicide, evidence for effective interventions is missing. The aim of this study was to examine whether psychosocial therapy after self-harm was linked to lower risks of repeated self-harm, suicide, and general mortality. METHODS: In this matched cohort study all people who, after deliberate self-harm, received a psychosocial therapy intervention at suicide prevention clinics in Denmark during 1992-2010 were compared with people who did not receive the psychosocial therapy intervention after deliberate self-harm. We applied propensity score matching with a 1:3 ratio and 31 matching factors, and calculated odds ratios for 1, 5, 10, and 20 years of follow-up. The primary endpoints were repeated self-harm, death by suicide, and death by any cause. FINDINGS: 5678 recipients of psychosocial therapy (followed up for 42.828 person-years) were matched with 17,034 individuals with no psychosocial therapy in a 1:8 ratio. During 20 year follow-up, 937 (16.5%) recipients of psychosocial therapy repeated the act of self-harm, and 391 (6.9%) died, 93 (16%) by suicide. The psychosocial therapy intervention was linked to lower risks of self-harm than was no psychosocial therapy (odds ratio [OR] 0.73, 95% CI 0.65-0.82) and death by any cause (0.62, 0.47-0.82) within a year. Long-term effects were identified for repeated self harm (0.84, 0.77-0.91; absolute risk reduction [ARR] 2.6%, 1.5-3.7; numbers needed to treat [NNT] 39, 95% CI 27-69), deaths by suicide (OR 0.75, 0.60-0.94; ARR 0.5%, 0.1-0.9; NNT 188, 108-725), and death by any cause (OR 0.69, 0.62-0.78; ARR 2.7%, 2.0-3.5; NNT 37, 29-52), implying that 145 self-harm episodes and 153 deaths, including 30 deaths by suicide, were prevented. INTERPRETATION: Our findings show a lower risk of repeated deliberate self-harm and general mortality in recipients of psychosocial therapy after short-term and long-term follow-up, and a protective effect for suicide after long-term follow-up, which favour the use of psychosocial therapy interventions after deliberate self-harm. FUNDING: Danish Health Insurance Foundation; the Research Council of Psychiatry, Region of Southern Denmark; the Research Council of Psychiatry, Capital Region of Denmark; and the Strategic Research Grant from Health Sciences, Capital Region of Denmark. PMID- 26359614 TI - A personal 35 year perspective on Gilles de la Tourette syndrome: prevalence, phenomenology, comorbidities, and coexistent psychopathologies. AB - This Series is a personal narrative of my experience with patients with Gilles de la Tourette syndrome and covers its definition and history since the first description in 1825. Controversy entered the prevalence debate early. Although originally considered very rare, in the 1980s, Tourette's syndrome was reported to be common. However, Tourette's syndrome has been shown to occur at a prevalence of about 0.85% to 1%. Tourette's syndrome is more common in the male population, more prominent during childhood, and usually improves, but does not disappear with age. Tourette's syndrome is considered less common in people of sub-Saharan black African, African-American, and American Hispanic ethnic origin. The phenomenology is similar worldwide, indicating a biological basis. The hallmark characteristics are multiple motor and one or more vocal/phonic tics. Other associated features include premonitory urges, a waxing and waning course, and to a much lesser degree, coprolalia. Comorbid disorders are common and are suggested to include obsessive-compulsive disorder and behaviours, attention deficit hyperactivity disorder, and autistic spectrum disorder. Coexistent psychopathologies are suggested to include depression and conduct and personality disorders. Importantly, I argue that Tourette's syndrome is not a unitary condition. Finally, I offer suggestions for future research. PMID- 26359613 TI - Heterogeneity of postpartum depression: a latent class analysis. AB - BACKGROUND: Maternal depression in the postpartum period confers substantial morbidity and mortality, but the definition of postpartum depression remains controversial. We investigated the heterogeneity of symptoms with the aim of identifying clinical subtypes of postpartum depression. METHODS: Data were aggregated from the international perinatal psychiatry consortium Postpartum Depression: Action Towards Causes and Treatment, which represents 19 institutions in seven countries. 17,912 unique subject records with phenotypic data were submitted. We applied latent class analyses in a two-tiered approach to assess the validity of empirically defined subtypes of postpartum depression. Tier one assessed heterogeneity in women with complete data on the Edinburgh postnatal depression scale (EPDS) and tier two in those with postpartum depression case status. FINDINGS: 6556 individuals were assessed in tier one and 4245 in tier two. A final model with three latent classes was optimum for both tiers. The most striking characteristics associated with postpartum depression were severity, timing of onset, comorbid anxiety, and suicidal ideation. Women in class 1 had the least severe symptoms (mean EPDS score 10.5), followed by those in class 2 (mean EPDS score 14.8) and those in class 3 (mean EPDS score 20.1). The most severe symptoms of postpartum depression were significantly associated with poor mood (mean EPDS score 20.1), increased anxiety, onset of symptoms during pregnancy, obstetric complications, and suicidal ideation. In class 2, most women (62%) reported symptom onset within 4 weeks postpartum and had more pregnancy complications than in other two classes (69% vs 67% in class 1 and 29% in class 3). INTERPRETATION: PPD seems to have several distinct phenotypes. Further assessment of PPD heterogeneity to identify more precise phenotypes will be important for future biological and genetic investigations. FUNDING: Sources of funding are listed at the end of the article. PMID- 26359615 TI - A personal 35 year perspective on Gilles de la Tourette syndrome: assessment, investigations, and management. AB - After having examined the definition, clinical phenomenology, comorbidity, psychopathology, and phenotypes in the first paper of this Series, here I discuss the assessment, including neuropsychology, and the effects of Gilles de la Tourette syndrome with studies showing that the quality of life of patients with Tourette's syndrome is reduced and that there is a substantial burden on the family. In this paper, I review my local and collaborative studies investigating causal factors (including genetic vulnerability, prenatal and perinatal difficulties, and neuro-immunological factors). I also present my studies on neuro-imaging, electro-encephalograms, and other special investigations, which are helpful in their own right or to exclude other conditions. Finally, I also review our studies on treatment including medications, transcranial magnetic stimulation, biofeedback, target-specific botulinum toxin injections, biofeedback and, in severe refractory adults, psychosurgery and deep brain stimulation. This Review summarises and highlights selected main findings from my clinic (initially The National Hospital for Neurology and Neurosurgery Queen Square and University College London, UK, and, subsequently, at St George's Hospital, London, UK), and several collaborations since 1980. As in Part 1 of this Series, I address the main controversies in the fields and the research of other groups, and I make suggestions for future research. PMID- 26359616 TI - The brain disease model of addiction: is it supported by the evidence and has it delivered on its promises? AB - Since 1997 the US National Institute on Drug Abuse has advocated a brain disease model of addiction (BDMA). We assess the strength of evidence for the BDMA in animals, neuroimaging studies of people with addiction, and current research on the role of genetics in addiction. We critically assess claims about the medical and social benefits of use of the BDMA because the social implications are often implied as a reason to accept this model. Furthermore, we argue that the BDMA is not supported by animal and neuroimaging evidence to the extent its advocates suggest; it has not helped to deliver more effective treatments for addiction; and its effect on public policies toward drugs and people with addiction has been modest. The focus of the BDMA is on disordered neurobiology in a minority of severely addicted individuals, which undermines the implementation of effective and cost-effective policies at the population level to discourage people from smoking tobacco and drinking heavily. The pursuit of high technology direct brain interventions to cure addiction when most individuals with addiction do not have access to effective psychosocial and drug treatments is questionable. PMID- 26359617 TI - The diagnosis debate: professional responsibility. PMID- 26359618 TI - Teaching global mental health at home and abroad. PMID- 26359619 TI - Midterm Follow-Up of Talectomy for Severe Rigid Equinovarus Feet. AB - Rigid equinovarus foot is a challenging problem. Talectomy has been advocated as a salvage procedure to achieve a plantigrade painless foot in the treatment of rigid equinovarus deformity. The present prospective observational study evaluated the effectiveness of talectomy in the treatment of Dimeglio grade IV rigid equinovarus feet. Nineteen feet in 13 patients were treated by talectomy from September 2001 through January 2012 (10-year, 2-month period). Of the 13 patients, 9 (69.23%) had a foot deformity due to arthrogryposis multiplex congenita and 1 (7.69%) each due to sacral agenesis, spastic cerebral palsy, neglected congenital talipes equinovarus, and post-traumatic contracture. Of the 13 patients, 9 (69.23%) were male and 4 (30.77%) were female. Their mean age was 7.7 (range 3 to 26) years. The mean follow-up duration was 6.4 (range 2 to 11) years. Along with talectomy, excision of the navicular was performed in 8 feet (42.11%), calcaneal osteotomy with a laterally based wedge in 8 (42.11%), and calcaneocuboid fusion in 3 feet (15.79%). Postoperatively, all the feet improved to Dimeglio grade II and were painless, and 16 feet (84.22%) were plantigrade; 1 foot (5.26%) had residual equinus resulting from incomplete removal of the talus and 2 (10.53%) had residual varus. Also, 3 feet (15.79%) had forefoot adduction (2 residual and 1 recurrent) that required a second surgery to correct the deformity. From our experience, talectomy is an effective procedure for correction of severe rigid equinovarus feet, provided that the talus is completely removed and the calcaneus is positioned correctly in the ankle mortise. PMID- 26359620 TI - Radiographic Relevance of the Distal Medial Cuneiform Angle in Hallux Valgus Assessment. AB - The angle formed by the distal articular facet of the medial cuneiform has been evaluated and discussed by various investigators. However, no consistent method has been available to radiograph and measure this entity. The wide variability of the angle is not conducive to comparative analysis. Additionally, investigators have noted that the angles observed (obliquity) vary greatly because of changes in radiographic angle, foot position, rotation of the first ray, and declination of the first metatarsal. Recognizing that these variables exist, we propose a reproducible assessment using digital radiography and application of deformity of correction principles. Our results have indicated a mean distal medial cuneiform angle of 20.69 degrees in normal feet, 23.51 degrees with moderate hallux valgus, and 20.41 degrees with severe hallux valgus deformity. The radiograph beam was kept at 15 degrees from the coronal plane. An inverse relationship was found between the distal medial cuneiform angle and bunion severity. This was in contrast to our expected hypothesis. The overall angle of the first metatarsal medial cuneiform did, however, correlate with the severity of the bunion deformity (p < .000). The obliquity values and intermetatarsal angles changed in direct relationship to the radiographic projection angle. This illustrates the importance of using standardized radiographic projection angles. We conclude that the 1-dimensional standard anteroposterior radiograph with assessment of the distal medial cuneiform angle cannot adequately demonstrate the pathologic features of hallux valgus. A better indicator appears to be the first metatarsal medial cuneiform angle. This pathologic entity is a 3-dimensional one that incorporates the joint morphology of the first ray, triplane osseous positioning, and soft tissue imbalances. Perhaps, 3-dimensional computed tomography imaging will provide better insight into this entity. PMID- 26359621 TI - Asymptomatic Congenital Absence of Lateral Pedal Rays. AB - Complete absence of 1 or more pedal rays is a rare condition. In the present report, the case of an adult male with complete congenital absence of his right fourth and fifth pedal rays is described. The condition had been asymptomatic until he had sustained an acute third metatarsal fracture and was satisfactorily treated with cast immobilization. PMID- 26359622 TI - Does First Nations ancestry modify the association between gestational diabetes and subsequent diabetes: a historical prospective cohort study among women in Manitoba, Canada. AB - BACKGROUND: Over the past 30 years, the prevalence of diabetes has steadily increased among Canadians, and is particularly evident among First Nations (FN) women. The interplay between FN ancestry, gestational diabetes and the development of subsequent diabetes among mothers remains unclear. METHODS: After excluding known pre-existing diabetes, we explored whether FN ancestry may modify the association between gestational diabetes and post-partum diabetes among women in Manitoba (1981-2011) via a historical prospective cohort database study. We analysed administrative data in the Population Health Research Data Repository using Kaplan-Meier survival analysis and Cox proportional hazards regression. RESULTS: Gestational diabetes was diagnosed in 11 906 of 404 736 deliveries (2.9%), 6.7% of FN and 2.2% of non-FN pregnant women (P < 0.0001). Post-partum diabetes during <= 30 years follow-up was more than three times higher among FN women than among non-FN women (P < 0.0001). Diabetes developed in 76.0% of FN and 56.2% of non-FN women with gestational diabetes within the follow-up period. The hazard ratio of gestational diabetes for post-partum diabetes was 10.6 among non FN women and 5.4 among FN women. Other factors associated with a higher risk of diabetes included lower family income among FN and non-FN women and rural/remote residences among FN women. Among non-FN women, urban residence was associated with a higher risk of diabetes. CONCLUSION: Gestational diabetes increases post partum diabetes in FN and non-FN women. FN women had substantially more gestational diabetes or post-partum diabetes than non-FN women, partially due to socio-economic and environmental barriers. Reductions in gestational diabetes and socio-economic inequalities are required to prevent diabetes in women, particularly in FN population. PMID- 26359624 TI - Association between nonsteroidal anti-inflammatory drugs and Clostridium difficile-associated diarrhea: A systematic review and meta-analysis. PMID- 26359623 TI - Monitoring Diabetic Nephropathy by Circulating Gangliosides. AB - Gangliosides are multifunctional molecules, abundantly expressed in renal cell membrane but also in sera of patients with renal disease. The aim of this study was to quantify the serum levels of sialic acid-ganglioside in patients diagnosed with diabetes for an eventual biomarker stratification of patients with renal complications. We included 35 diabetic patients without metabolic complications, 35 patients with diabetic nephropathy, 35 non-diabetic individuals. We found that sialic acid ganglioside serum level was significantly increased in patients with diabetic nephropathy compared to the level obtained in patients with uncomplicated diabetes and to non-diabetic controls. A statistically significant positive correlation was obtained between serum levels of sialic acid gangliosides, HbA1c, and serum creatinine in patients with diabetes without complications. Moreover positive correlation was found between sialic acid ganglioside and blood glucose, HbA1c, urea, creatinine, microalbuminuria in patients with diabetic nephropathy. We can conclude that serum sialic acid gangliosides are statistically increased in diabetic nephropathy positively correlated with microalbuminuria. PMID- 26359625 TI - Cloxacillin - A new cause of pill-induced esophagitis. PMID- 26359626 TI - Cancer stem cell invasion of the hepatic microvasculature as a predictor of tumour recurrence following surgical resection in adult patients with hepatocellular carcinoma. PMID- 26359627 TI - Development of a robust DNA damage model including persistent telomere-associated damage with application to secondary cancer risk assessment. AB - Mathematical modelling has been instrumental to understand kinetics of radiation induced DNA damage repair and associated secondary cancer risk. The widely accepted two-lesion kinetic (TLK) model assumes two kinds of double strand breaks, simple and complex ones, with different repair rates. Recently, persistent DNA damage associated with telomeres was reported as a new kind of DNA damage. We therefore extended existing versions of the TLK model by new categories of DNA damage and re-evaluated those models using extensive data. We subjected different versions of the TLK model to a rigorous model discrimination approach. This enabled us to robustly select a best approximating parsimonious model that can both recapitulate and predict transient and persistent DNA damage after ionizing radiation. Models and data argue for i) nonlinear dose-damage relationships, and ii) negligible saturation of repair kinetics even for high doses. Additionally, we show that simulated radiation-induced persistent telomere associated DNA damage foci (TAF) can be used to predict excess relative risk (ERR) of developing secondary leukemia after fractionated radiotherapy. We suggest that TAF may serve as an additional measure to predict cancer risk after radiotherapy using high dose rates. This may improve predicting risk-dose dependency of ionizing radiation especially for long-term therapies. PMID- 26359628 TI - Why semicarbazide (SEM) is not an appropriate marker for the usage of nitrofurazone on agricultural animals. AB - A comprehensive global database on semicarbazide (SEM) in foodstuffs and food ingredients is presented, with over 4000 data collected in foods such as seafood (crustaceans, fish powders), meat (beef, chicken powders), dairy products (e.g. raw milk, milk powders, whey, sweet buttermilk powder, caseinate, yoghurt, cheese), honey and other ingredients. The results provide evidence that the presence of SEM in certain dairy ingredients (whey, milk protein concentrates) is a by-product of chemical reactions taking place during the manufacturing process. Of the dairy ingredients tested (c. 2000 samples), 5.3% showed traces of SEM > 0.5 ug/kg. The highest incidence of SEM-positive samples in the dairy category were whey (powders, liquid) and milk protein concentrates (35% positive), with up to 13 ug/kg measured in a whey powder. Sweet buttermilk powder and caseinate followed, with 27% and 9.3% positives, respectively. SEM was not detected in raw milk, or in yoghurt or cheese. Of the crustacean products (shrimp and prawn powders) tested, 44% were positive for SEM, the highest value measured at 284 ug/kg. Fish powders revealed an unexpectedly high incidence of positive samples (25%); in this case, fraudulent addition of shellfish shells or carry-over during processing cannot be excluded. Overall, the data provide new insights into the occurrence of SEM (for dairy products and fish powders), substantially strengthening the arguments that SEM in certain food categories is not a conclusive marker of the use of the illegal antibiotic nitrofurazone. PMID- 26359630 TI - Brief report: cervical cancer screening in women with intellectual and developmental disabilities who have had a pregnancy. AB - BACKGROUND: Women with intellectual and developmental disabilities (IDD) have lower cervical cancer screening rates than women without IDD. Key barriers to screening uptake include physician or caregiver assumptions that screening is unnecessary because women with IDD are not sexually active. Our objective was to compare cervical cancer screening rates in women with and without IDD who had had a pregnancy. METHOD: We conducted a population-based retrospective cohort study using linked Ontario (Canada) health and social services administrative data. We identified 20- to 64-year-old women with (N = 5033) and without (N = 527 437) IDD who had had a pregnancy. We examined the occurrence of cervical cancer screening between April 1, 2007 and March 31, 2010. We compared screening rates in women with and without IDD using logistic regression, controlling for age, region of residence, neighbourhood income quintile and morbidity level. RESULTS: Women with IDD who had had a pregnancy were more likely than those without IDD to be young, to live in the lowest neighbourhood income quintile, to live in rural areas and to have high or very high morbidity. Even after controlling for these factors, women with IDD were less likely than women without IDD to be screened (67.7% vs. 77.0%; adjusted odds ratio 0.61; 95% confidence interval 0.58-0.65). CONCLUSIONS: Even among women who have had a pregnancy and are therefore known to have been sexually active, women with IDD face significant disparities in cervical cancer screening. Strategies to promote equitable uptake of cervical cancer screening for women with IDD need to be implemented. PMID- 26359631 TI - Graphene as an Interfacial Layer for Improving Cycling Performance of Si Nanowires in Lithium-Ion Batteries. AB - Managing interfacial instability is crucial for enhancing cyclability in lithium ion batteries (LIBs), yet little attention has been devoted to this issue until recently. Here, we introduce graphene as an interfacial layer between the current collector and the anode composed of Si nanowires (SiNWs) to improve the cycling capability of LIBs. The atomically thin graphene lessened the stress accumulated by volumetric mismatch and inhibited interfacial reactions that would accelerate the fatigue of Si anodes. By simply incorporating graphene at the interface, we demonstrated significantly enhanced cycling stability for SiNW-based LIB anodes, with retentions of more than 2400 mAh/g specific charge capacity over 200 cycles, 2.7 times that of SiNWs on a bare current collector. PMID- 26359629 TI - Rigorous optimization and validation of potent RNA CAR T cell therapy for the treatment of common epithelial cancers expressing folate receptor. AB - Using lentiviral technology, we recently demonstrated that incorporation of CD27 costimulation into CARs greatly improves antitumor activity and T cell persistence. Still, virus-mediated gene transfer is expensive, laborious and enables long-term persistence, creating therapies which cannot be easily discontinued if toxic. To address these concerns, we utilized a non-integrating RNA platform to engineer human T cells to express FRalpha-specific, CD27 CARs and tested their capacity to eliminate human FRalpha(+) cancer. Novel CARs comprised of human components were constructed, C4-27z and C4opt-27z, a codon-optimized variant created for efficient expression. Following RNA electroporation, C4-27z and C4opt-27z CAR expression is initially ubiquitous but progressively declines across T cell populations. In addition, C4-27z and C4opt-27z RNA CAR T cells secrete high levels of Th-1 cytokines and display strong cytolytic function against human FRalpha(+) cancers in a time- and antigen-dependent manner. Further, C4-27z and C4opt-27z CAR T cells exhibit significant proliferation in vivo, facilitate the complete regression of fully disseminated human ovarian cancer xenografts in mice and reduce the progression of solid ovarian cancer. These results advocate for rapid progression of C4opt-27z RNA CAR to the clinic and establish a new paradigm for preclinical optimization and validation of RNA CAR candidates destined for clinical translation. PMID- 26359632 TI - Lesion Size and Safety Comparison Between the Novel Flex Tip on the FlexAbility Ablation Catheter and the Solid Tips on the ThermoCool and ThermoCool SF Ablation Catheters. AB - INTRODUCTION: Next-generation catheters have been developed to reduce irrigation volume and preserve power delivery. A novel design uses a flexible tip (FlexAbilityTM catheter) that directs flow to the contact surface. Because of recent safety issues with new catheters, we undertook a study in a canine heart with 3 irrigated catheters to compare efficacy and safety. METHODS: Endocardial ablation was performed by 2 independent operators in 12 anesthetized canines with the FlexAbility (St. Jude Medical), ThermoCoolTM (Biosense Webster), and ThermoCoolTM SF (Biosense Webster) catheters. Endocardial RF lesions were delivered with each catheter in all 4 chambers of each animal for 52 +/- 16 seconds. Each chamber was randomized to receive ablation from one catheter with recording of safety events. Cardiac pathology was performed with triphenyl tetrazolium chloride stain. RESULTS: Average lesion dimensions were not significantly different between the 3 catheters. FlexAbilityTM demonstrated a lower risk of steam pops relative to ThermoCool SF (P-value = 0.013) despite equal mean power and radiofrequency time. High-temperature generator shutdowns were observed with FlexAbilityTM but not with either ThermoCool catheter. High temperature shutdowns were associated with larger average impedance drops (28.5 ohms vs. 19 ohms) without compromising lesion size. CONCLUSIONS: The FlexAbilityTM tip is safe and effective with no significant difference in lesion sizes compared to both standard ThermoCool and ThermoCool SF. FlexAbilityTM has a significantly lower risk of steam pops compared to ThermoCool SF in a beating heart as defined predominantly by an abrupt rise of impedance. PMID- 26359633 TI - Cell type-specific pharmacology of NMDA receptors using masked MK801. AB - N-Methyl-D-aspartate receptors (NMDA-Rs) are ion channels that are important for synaptic plasticity, which is involved in learning and drug addiction. We show enzymatic targeting of an NMDA-R antagonist, MK801, to a molecularly defined neuronal population with the cell-type-selectivity of genetic methods and the temporal control of pharmacology. We find that NMDA-Rs on dopamine neurons are necessary for cocaine-induced synaptic potentiation, demonstrating that cell type specific pharmacology can be used to dissect signaling pathways within complex brain circuits. PMID- 26359634 TI - Water-mediated recognition of t1-adenosine anchors Argonaute2 to microRNA targets. AB - MicroRNAs (miRNAs) direct post-transcriptional regulation of human genes by guiding Argonaute proteins to complementary sites in messenger RNAs (mRNAs) targeted for repression. An enigmatic feature of many conserved mammalian miRNA target sites is that an adenosine (A) nucleotide opposite miRNA nucleotide-1 confers enhanced target repression independently of base pairing potential to the miRNA. In this study, we show that human Argonaute2 (Ago2) possesses a solvated surface pocket that specifically binds adenine nucleobases in the 1 position (t1) of target RNAs. t1A nucleotides are recognized indirectly through a hydrogen bonding network of water molecules that preferentially interacts with the N6 amine on adenine. t1A nucleotides are not utilized during the initial binding of Ago2 to its target, but instead function by increasing the dwell time on target RNA. We also show that N6 adenosine methylation blocks t1A recognition, revealing a possible mechanism for modulation of miRNA target site potency. PMID- 26359636 TI - The Australian litigation landscape - oral and maxillofacial surgery and general dentistry (oral surgery procedures): an analysis of litigation cases. AB - BACKGROUND: There are persistent concerns about litigation in the dental and medical professions. These concerns arise in a setting where general dentists are more frequently undertaking a wider range of oral surgery procedures, potentially increasing legal risk. METHODS: Judicial cases dealing with medical negligence in the fields of general dentistry (oral surgery procedure) and oral and maxillofacial surgery were located using the three main legal databases. Relevant cases were analysed to determine the procedures involved, the patients' claims of injury, findings of negligence and damages awarded. A thematic analysis of the cases was undertaken to determine trends. RESULTS: Fifteen cases over a 20-year period were located across almost all Australian jurisdictions (eight cases involved general dentists; seven cases involved oral and maxillofacial surgeons). Eleven of the 15 cases involved determinations of whether or not the practitioner had failed in their duty of care; negligence was found in six cases. Eleven of the 15 cases related to molar extractions (eight specifically to third molar). CONCLUSIONS: Dental and medical practitioners wanting to manage legal risk should have regard to circumstances arising in judicial cases. Adequate warning of risks is critical, as is offering referral in appropriate cases. Preoperative radiographs, good medical records and processes to ensure appropriate follow-up are also important. PMID- 26359635 TI - Characterization of the finch embryo supports evolutionary conservation of the naive stage of development in amniotes. AB - Innate pluripotency of mouse embryos transits from naive to primed state as the inner cell mass differentiates into epiblast. In vitro, their counterparts are embryonic (ESCs) and epiblast stem cells (EpiSCs), respectively. Activation of the FGF signaling cascade results in mouse ESCs differentiating into mEpiSCs, indicative of its requirement in the shift between these states. However, only mouse ESCs correspond to the naive state; ESCs from other mammals and from chick show primed state characteristics. Thus, the significance of the naive state is unclear. In this study, we use zebra finch as a model for comparative ESC studies. The finch blastoderm has mESC-like properties, while chick blastoderm exhibits EpiSC features. In the absence of FGF signaling, finch cells retained expression of pluripotent markers, which were lost in cells from chick or aged finch epiblasts. Our data suggest that the naive state of pluripotency is evolutionarily conserved among amniotes. PMID- 26359637 TI - Using the matrix-induced ion suppression method for concentration normalization in cellular metabolomics studies. AB - Studies of the cell metabolome greatly improve our understanding of cell biology. Currently, most cellular metabolomics studies control only cell numbers or protein content without adjusting the total metabolite concentration, mainly because of the lack of an effective concentration normalization method for cell metabolites. This study proposed a matrix-induced ion suppression (MIIS) method to measure the total amount of cellular metabolites by utilizing flow injection analysis coupled with electrospray ionization mass spectrometry (FIA-ESI-MS).We used series dilutions of HL-60 cell extracts to establish the relationship between cellular metabolite concentration and the degree of ion suppression of the ion suppression indicator, and a good correlation was obtained between 2- and 12-fold dilutions of cell extracts (R(2) = 0.999). Two lung cancer cells, CL1-0 and CL1-5, were selected as the model cell lines to evaluate the efficacy of the MIIS method and the importance of metabolite concentration normalization. Through MIIS analysis, CL1-0 cells were found to contain metabolites at a concentration 2.1 times higher than in CL1-5, and the metastatic properties of CL1-5 could only be observed after 2.1-fold dilution of CL1-0 before metabolomic analysis. Our results demonstrated that the MIIS method is an effective approach for metabolite concentration normalization and that controlling metabolite concentrations can improve data integrity in cellular metabolomics studies. PMID- 26359638 TI - The role of ABC genes in shaping perianth phenotype in the basal angiosperm Magnolia. AB - It is generally accepted that the genus Magnolia is characterised by an undifferentiated perianth, typically organised into three whorls of nearly identical tepals. In some species, however, we encountered interesting and significant perianth modifications. In Magnolia acuminata, M. liliiflora and M. stellata the perianth elements of the first whorl are visually different from the others. In M. stellata the additional, spirally arranged perianth elements are present above the first three whorls, which suggests that they have been formed within the domain of stamen primordia. In these three species, we analysed expression patterns of the key flower genes (AP1, AGL6, AP3, PI, AG) responsible for the identity of flower elements and correlated them with results of morphological and anatomical investigations. In all studied species the elements of the first whorl lacked the identity of petals (lack of AP3 and PI expression) but also that of leaves (presence of AGL6 expression), and this seems to prove their sepal character. The analysis of additional perianth elements of M. stellata, spirally arranged on the elongated floral axis, revealed overlapping and reduced activity of genes involved in specification of the identity of the perianth (AGL6) but also of generative parts (AG), even though no clear gradient of morphological changes could be observed. In conclusion, Magnolia genus is capable of forming, in some species, a perianth differentiated into a calyx (sepals) and corolla (petals). Spirally arranged, additional perianth elements of M. stellata, despite activity of AG falling basipetally, resemble petals. PMID- 26359639 TI - Chd5 Regulates MuERV-L/MERVL Expression in Mouse Embryonic Stem Cells Via H3K27me3 Modification and Histone H3.1/H3.2. AB - Chd5 is an essential factor for neuronal differentiation and spermatogenesis and is a known tumor suppressor. H3K27me3 and H3K4un are modifications recognized by Chd5; however, it remains unclear how Chd5 remodels chromatin structure. We completely disrupted the Chd5 locus using the CRISPR-Cas9 system to generate a 52 kbp long deletion and analyzed Chd5 function in mouse embryonic stem cells. Our findings show that Chd5 represses murine endogenous retrovirus-L (MuERV-L/MERVL), an endogenous retrovirus-derived retrotransposon, by regulating H3K27me3 and H3.1/H3.2 function. PMID- 26359640 TI - Neospora caninum in crows from Israel. AB - A cross-sectional Neospora caninum seroprevalence study was performed on free ranging crows (Corvus cornix, Corvus monedula and Corvus splendens) from Israel in order to assess their exposure to this pathogen and evaluate their role as potential hosts or as sentinels of infection. Using the modified agglutination test (MAT) with a cutoff titer of 1:100, 30 out of 183 crows (16.4%) were found to be N. caninum seropositive. Positive results were validated and confirmed by the indirect fluorescent antibody test (IFAT). There was 100% agreement between tests when cut-off titers of 1:50 and 1:100 were applied for the IFAT and MAT, respectively. PCR analysis of brain extracts from all crows resulted in the detection of N. caninum DNA for the first time in crows belonging to two species, C. cornix and C. monedula. The high N. caninum seroprevalence in crows suggests that widespread exposure to infection with N. caninum exists especially in central and northern Israel and that crows may act as suitable markers for disease prevalence in the areas in which they are found. PMID- 26359641 TI - Acaricidal properties of vetiver essential oil from Chrysopogon zizanioides (Poaceae) against the tick species Amblyomma cajennense and Rhipicephalus (Boophilus) microplus (Acari: Ixodidae). AB - Ticks are arthropods widely distributed in tropical and subtropical regions, which can transmit infectious agents also responsible for zoonoses. Excessive use of conventional acaricides has resulted in the onset of drug resistance by these parasites, thus the need to use alternative methods for their control. This study evaluated the acaricidal activities of Chrysopogon zizanioides (vetiver) essential oils containing different zizanoic and khuzimol (high and low acidity) acid concentrations on Amblyomma cajennense and Rhipicephalus microplus (Acari: Ixodidae). To this aims, toxicity tests of different concentrations of examined essential oils were conducted on adult females and larval stages. Results showed that the essential oils of C. zizanioides with high and low acidity reduced oviposition of females, eggs hatch and larval survival, being more effective than some commercial products widely used to control these ectoparasites. These results indicate that the C. zizanoides essential oils are promising candidates as acaricidal agents and represent also an add value to vetiver oil with high acidity, which is commercially undervalued in the cosmetic industry. PMID- 26359644 TI - APETALA1 establishes determinate floral meristem through regulating cytokinins homeostasis in Arabidopsis. PMID- 26359642 TI - Content of intrinsic disorder influences the outcome of cell-free protein synthesis. AB - Cell-free protein synthesis is used to produce proteins with various structural traits. Recent bioinformatics analyses indicate that more than half of eukaryotic proteins possess long intrinsically disordered regions. However, no systematic study concerning the connection between intrinsic disorder and expression success of cell-free protein synthesis has been presented until now. To address this issue, we examined correlations of the experimentally observed cell-free protein expression yields with the contents of intrinsic disorder bioinformatically predicted in the expressed sequences. This analysis revealed strong relationships between intrinsic disorder and protein amenability to heterologous cell-free expression. On the one hand, elevated disorder content was associated with the increased ratio of soluble expression. On the other hand, overall propensity for detectable protein expression decreased with disorder content. We further demonstrated that these tendencies are rooted in some distinct features of intrinsically disordered regions, such as low hydrophobicity, elevated surface accessibility and high abundance of sequence motifs for proteolytic degradation, including sites of ubiquitination and PEST sequences. Our findings suggest that identification of intrinsically disordered regions in the expressed amino acid sequences can be of practical use for predicting expression success and optimizing cell-free protein synthesis. PMID- 26359645 TI - Tackling the hepatitis C cost problem: A test case for tomorrow's cures. PMID- 26359646 TI - The utility of ADAMTS13 in differentiating TTP from other acute thrombotic microangiopathies: results from the UK TTP Registry. AB - Thrombotic microangiopathies (TMAs) are frequently difficult to differentiate clinically, and measurement of ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) remains vital in thrombotic thrombocytopenic purpura (TTP) diagnosis. We retrospectively reviewed cases referred for ADAMTS13 testing, using UK TTP Registry screening data. Of a total 810 cases, 350 were confirmed as TTP. The 460 non-TTP cases comprised secondary TMAs (24.57%) and haemolytic uraemic syndrome (HUS) (27.17% aHUS, 2.83% Shiga like toxin-producing E. coli [STEC]-HUS); the remainder were TMAs with no clear association, not TMAs, or had no confirmed diagnosis. ADAMTS13 levels were significantly lower in TTP than STEC-HUS, aHUS and other TMAs. TTP patients had significantly lower platelet count (15 * 10(9) /l; range 0-96) than aHUS (57 * 10(9) /l; range 13-145, P < 0.0001) or STEC-HUS (35 * 10(9) /l; range 14-106, P < 0.0001); they also had lower creatinine levels (92 MUmol/l; range 43-374) than aHUS (255 MUmol/l; range 23-941, P < 0.0001) and STEC-HUS (324 MUmol/l; range 117 639, P < 0.0001). However, 12/34 (35.3%) aHUS patients had a platelet count <30 * 10(9) /l and 26/150 (17.3%) of TTP patients had a platelet count >30 * 10(9) /l; 23/150 (15.3%) of TTP patients had a creatinine level >150 MUmol/l. This study highlights the wide variety of TMA presentations, and confirms the utility of ADAMTS13 testing in TTP diagnosis. PMID- 26359647 TI - Autoantibodies in autoimmune liver diseases. AB - Autoimmune hepatitis is a chronic hepatitis of unknown etiology characterized by clinical, histological, and immunological features, generally including circulating autoantibodies and a high total serum and/or gamma globulin. Liver related autoantibodies are very significant for the correct diagnosis and classification of autoimmune liver diseases (AILD), namely autoimmune hepatitis types 1 and 2 (AIH-1 and 2), primary biliary cirrhosis (PBC), and the sclerosing cholangitis types in adults and children. This article intends to review recent studies that investigate autoantibodies in autoimmune liver diseases from a microbiological perspective. PMID- 26359648 TI - Quasi-simultaneous multimodal imaging of cutaneous tissue oxygenation and perfusion. AB - Simultaneous and quantitative assessment of multiple tissue parameters may facilitate more effective diagnosis and therapy in many clinical applications, such as wound healing. However, existing wound assessment methods are typically subjective and qualitative, with the need for sequential data acquisition and coregistration between modalities, and lack of reliable standards for performance evaluation or calibration. To overcome these limitations, we developed a multimodal imaging system for quasi-simultaneous assessment of cutaneous tissue oxygenation and perfusion in a quantitative and noninvasive fashion. The system integrated multispectral and laser speckle imaging technologies into one experimental setup. Tissue oxygenation and perfusion were reconstructed by advanced algorithms. The accuracy and reliability of the imaging system were quantitatively validated in calibration experiments and a tissue-simulating phantom test. The experimental results were compared with a commercial oxygenation and perfusion monitor. Dynamic detection of cutaneous tissue oxygenation and perfusion was also demonstrated in vivo by a postocclusion reactive hyperemia procedure in a human subject and a wound healing process in a wounded mouse model. Our in vivo experiments not only validated the performance of the multimodal imaging system for cutaneous tissue oxygenation and perfusion imaging but also demonstrated its technical potential for wound healing assessment in clinical practice. PMID- 26359650 TI - Serum antiphospholipid antibody level and ocular haemodynamics in eyes with pseudoexfoliation syndrome. PMID- 26359652 TI - Insertion/Rearrangement Reactivity of a Lutetacyclopentadiene towards N,N' Diphenylcarbodiimide: Cooperative Effect of the Metal Center, Concentration of LiCl, and Solvent. AB - The reactivity of lutetacyclopentadiene towards N,N'-diphenylcarbodiimide (DPC) was systematically investigated to efficiently construct three types of new N containing fused cyclic complexes. The outcome of these reactions significantly depended on the the metal center, the concentration of LiCl, the number of equivalents of DPC, and the solvent. Thus, two unexpected reaction modes of amidinate were discovered for the first time, which were ascribed to an unusual kappa(1) coordination mode of amidinate driven by a rigid seven-membered ring. These results are in striking contrast with the previously well-investigated zirconacyclopentadiene, which reacts with DPC to give azazirconacyclopentene and alkyne through beta,beta' C?C bond cleavage. The difference in reactivity between lutetacyclopentadiene and zirconacyclopentadiene can be attributed to the highly ionic character of the Lu?C(sp(2) ) bonds. DFT calculations agreed well with the experimental results. PMID- 26359651 TI - Infant Infections and Respiratory Symptoms in Relation to in Utero Arsenic Exposure in a U.S. Cohort. AB - BACKGROUND: Arsenic has been linked to disrupted immune function and greater infection susceptibility in highly exposed populations. Well arsenic levels above the U.S. EPA limit occur in our U.S. study area and are of particular concern for pregnant women and infants. OBJECTIVES: We investigated whether in utero arsenic exposure affects the risk of infections and respiratory symptoms over the first year of life. METHODS: We prospectively obtained information on infant infections and symptoms, including their duration and treatment (n = 412) at 4, 8, and 12 months using a parental telephone survey. Using generalized estimating equation models adjusted for potential confounders, we evaluated the association between maternal pregnancy urinary arsenic and infant infections and symptoms over the first year. RESULTS: Each doubling of maternal urinary arsenic was related to increases in the total number of infections requiring prescription medication in the first year [relative risk (RR) = 1.1; 95% CI: 1.0, 1.2]. Urinary arsenic was related specifically to respiratory symptoms (difficulty breathing, wheezing, and cough) lasting >= 2 days or requiring prescription medication (RR = 1.1; 95% CI: 1.0, 1.2; and RR = 1.2; 95% CI: 1.0, 1.5, respectively), and wheezing lasting >= 2 days, resulting in a doctor visit or prescription medication treatment (RR = 1.3; 95% CI: 1.0, 1.7; RR = 1.3; 95% CI: 1.0, 1.8, and RR = 1.5; 95% CI: 1.0, 2.2, respectively). Associations also were observed with diarrhea (RR = 1.4; 95% CI: 1.1, 1.9) and fever resulting in a doctor visit (RR = 1.2; 95% CI: 1.0, 1.5). CONCLUSIONS: In utero arsenic exposure was associated with a higher risk of infection during the first year of life in our study population, particularly infections requiring medical treatment, and with diarrhea and respiratory symptoms. CITATION: Farzan SF, Li Z, Korrick SA, Spiegelman D, Enelow R, Nadeau K, Baker E, Karagas MR. 2016. Infant infections and respiratory symptoms in relation to in utero arsenic exposure in a U.S. COHORT: Environ Health Perspect 124:840-847; http://dx.doi.org/10.1289/ehp.1409282. PMID- 26359649 TI - Strategies for the Optimization of Natural Leads to Anticancer Drugs or Drug Candidates. AB - Natural products have made significant contribution to cancer chemotherapy over the past decades and remain an indispensable source of molecular and mechanistic diversity for anticancer drug discovery. More often than not, natural products may serve as leads for further drug development rather than as effective anticancer drugs by themselves. Generally, optimization of natural leads into anticancer drugs or drug candidates should not only address drug efficacy, but also improve absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles and chemical accessibility associated with the natural leads. Optimization strategies involve direct chemical manipulation of functional groups, structure-activity relationship directed optimization and pharmacophore oriented molecular design based on the natural templates. Both fundamental medicinal chemistry principles (e.g., bioisosterism) and state-of-the-art computer-aided drug design techniques (e.g., structure-based design) can be applied to facilitate optimization efforts. In this review, the strategies to optimize natural leads to anticancer drugs or drug candidates are illustrated with examples and described according to their purposes. Furthermore, successful case studies on lead optimization of bioactive compounds performed in the Natural Products Research Laboratories at UNC are highlighted. PMID- 26359653 TI - Association of Body Mass Index With Incidence and Progression of Knee Effusion on Magnetic Resonance Imaging and on Knee Examination. AB - OBJECTIVE: To determine the association of body mass index (BMI) with incidence and progression of knee effusion on magnetic resonance imaging (MRI) and physical examination (PE) in a longitudinal cohort with knee pain. METHODS: A population based cohort was assessed at baseline and 3 years (n = 163). BMI was categorized as normal (<25), overweight (25-29.9), and obese (>=30). Knee effusion was graded as 0-3 (absent/mild/moderate/severe) on MRI and 0-1 (absent/present) on PE. Progression of MRI effusion (MRIeff ) was an increase of >=1 grade in those with grade 1 or 2 at baseline. Incident MRIeff and PE effusion (PEeff ) were any effusion at followup (>0) in those with grade 0 at baseline. A second type of incident MRIeff was effusion grade >=2 at followup in those with grade <2 at baseline. Exponential regression analysis was used, adjusted for age, sex, and radiographic severity. RESULTS: Incident MRIeff >=1, incident MRIeff >=2, incident PEeff , and progression of MRIeff were seen in 14 of 73 (19%), 18 of 140 (13%), 26 of 127 (20%), and 18 of 86 (21%), respectively. There was a borderline statistical association of obesity with progression of MRIeff (hazard ratio [HR] 3.3 [95% confidence interval (95% CI) 1.0-11.2]) and with incident MRIeff >=2 (HR 3.4 [95% CI 1.0-11.5]). BMI was not associated with incident MRIeff >=1 (HR overweight 1.1 [95% CI 0.3-3.6], obese 1.0 [95% CI 0.2-5.0]). Overweight was associated with incident PEeff (HR 4.5 [95% CI 1.4-14.2]), while obesity was not statistically significant (HR 3.1 [95% CI 0.9-11.1]). CONCLUSION: Obesity was a risk factor for incident and progressive knee effusion in this population-based cohort. These findings highlight an important link between obesity and inflammation in knee osteoarthritis. PMID- 26359654 TI - An In Vivo Evaluation of the Fit of Zirconium-Oxide Based, Ceramic Single Crowns with Vertical and Horizontal Finish Line Preparations. AB - PURPOSE: Different types of tooth preparations influence the marginal precision of zirconium-oxide based ceramic single crowns. In this in vivo study, the marginal fits of zirconium-oxide based ceramic single crowns with vertical and horizontal finish lines were compared. MATERIALS AND METHODS: Forty-six teeth were chosen in eight patients indicated for extraction for implant placement. CAD/CAM technology was used for the production of 46 zirconium-oxide-based ceramic single crowns: 23 teeth were prepared with vertical finishing lines, 23 with horizontal finishing lines. One operator accomplished all clinical procedures. The zirconia crowns were cemented with glass ionomer cement. The teeth were extracted 1 month later. Marginal gaps along vertical planes were measured for each crown, using a total of four landmarks for each tooth by means of a microscope at 50* magnification. On conclusion of microscopic assessment, ESEM evaluation was completed on all specimens. The comparison of the gap between the two types of preparation was performed with a nonparametric test (two-sample Wilcoxon rank-sum test) with a level of significance fixed at p < 0.05. All data were analyzed with STATA12. RESULTS: In the group with horizontal finish line preparations, the median value of the gap was 35.45 MUm (Iqr, 0.33); for the vertical finish line group, the median value of the gap was 35.44 MUm (Iqr, 0.40). The difference between the two groups was not statistically significant (two-sample Wilcoxon rank-sum test, p = 0.0872). CONCLUSIONS: Within the limitations of this study, the gaps of the zirconium-oxide-based ceramic CAD/CAM crowns with vertical and horizontal finish line preparations were not different. PMID- 26359655 TI - European Fissure Sealant Guidelines: assessment using AGREE II. AB - BACKGROUND: Pit and fissure sealants are effective in reducing the incidence of occlusal caries, and multiple clinical practice guidelines (CPGs) have been developed for recommending their proper use. The usefulness of CPGs depends on their quality and on the rigour of the guideline development process. OBJECTIVE: A study was made to assess the quality of current European CPGs based on the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument, which uses 23 key items rated on a 7-point scale to assess practice guideline development and the quality of reporting. METHODS: A search was conducted for fissure sealant guidelines for preventing caries in children and adults at high and low risk published in the last 10 years. Calibration was carried out before scoring to assess agreement between the appraisers using the AGREE II instrument. RESULTS: The searches identified 19 relevant guidelines, and following application of the inclusion/exclusion criteria, three guidelines were retained for evaluation. The proportion of observed agreement was calculated, expressed by the agreement separately for positive and negative ratings (PA = 0.89, NA = 0 91). The results of the guideline assessments revealed the highest score for the Irish guideline, a moderate score for the French guideline and the lowest score for the European guideline. CONCLUSIONS: Based on the AGREE II instrument, the results obtained show significant variation in the quality assessment of the three European Fissure Sealant Guidelines. Future studies should be carried out both to develop quality dental CPGs and to investigate effective ways of adopting them. PMID- 26359657 TI - The mechanism of CO2 hydration: a porous metal oxide nanocapsule catalyst can mimic the biological carbonic anhydrase role. AB - The mechanism for the hydration of CO2 within a Keplerate nanocapsule is presented. A network of hydrogen bonds across the water layers in the first metal coordination sphere facilitates the proton abstraction and nucleophilic addition of water. The highly acidic properties of the polyoxometalate cluster are crucial for explaining the catalysed hydration. PMID- 26359656 TI - Erdheim-Chester Disease. PMID- 26359658 TI - Cell and Tissue Damage after Skin Exposure to Ionizing Radiation: Short- and Long Term Effects after a Single and Fractional Doses. AB - Ionizing radiation is often used to treat progressive neoplasms. However, the consequences of long-term radiation exposure to healthy skin tissue are poorly understood. We aimed to evaluate the short- and long-term radiation damage to healthy skin of the same irradiation given either as single or fractional doses. C57BL/J6 mice were randomly assigned to one of three groups: a control and two exposure groups (5 Gy *2 or 10 Gy *1). The inguinal area was irradiated (6-MeV beam) 1 week after depilation in the treatment groups. Skin samples were evaluated macroscopically and histologically for up to 6 months after the final exposure. After anagen hair follicle injury by irradiation, hair cycling resumed in both groups, but hair graying was observed in the 10 Gy *1 group but not in the 5 Gy *2 group, suggesting the dose of each fractional exposure is more relevant to melanocyte stem cell damage than the total dose. On the other hand, in the long term, the fractional double exposures induced more severe atrophy and capillary reduction in the dermis and subcutis, suggesting fractional exposure may cause more depletion of tissue stem cells and endothelial cells in the tissue. Thus, our results indicated that there were differences between the degrees of damage that occurred as a result of a single exposure compared with fractional exposures to ionizing radiation: the former induces more severe acute injury to the skin with irreversible depigmentation of hairs, while the latter induces long-term damage to the dermis and subcutis. PMID- 26359659 TI - Spectrophotometric Analysis of Pigments: A Critical Assessment of a High Throughput Method for Analysis of Algal Pigment Mixtures by Spectral Deconvolution. AB - The Gauss-peak spectra (GPS) method represents individual pigment spectra as weighted sums of Gaussian functions, and uses these to model absorbance spectra of phytoplankton pigment mixtures. We here present several improvements for this type of methodology, including adaptation to plate reader technology and efficient model fitting by open source software. We use a one-step modeling of both pigment absorption and background attenuation with non-negative least squares, following a one-time instrument-specific calibration. The fitted background is shown to be higher than a solvent blank, with features reflecting contributions from both scatter and non-pigment absorption. We assessed pigment aliasing due to absorption spectra similarity by Monte Carlo simulation, and used this information to select a robust set of identifiable pigments that are also expected to be common in natural samples. To test the method's performance, we analyzed absorbance spectra of pigment extracts from sediment cores, 75 natural lake samples, and four phytoplankton cultures, and compared the estimated pigment concentrations with concentrations obtained using high performance liquid chromatography (HPLC). The deviance between observed and fitted spectra was generally very low, indicating that measured spectra could successfully be reconstructed as weighted sums of pigment and background components. Concentrations of total chlorophylls and total carotenoids could accurately be estimated for both sediment and lake samples, but individual pigment concentrations (especially carotenoids) proved difficult to resolve due to similarity between their absorbance spectra. In general, our modified-GPS method provides an improvement of the GPS method that is a fast, inexpensive, and high throughput alternative for screening of pigment composition in samples of phytoplankton material. PMID- 26359660 TI - Nutrient Distribution and Absorption in the Colonial Hydroid Podocoryna carnea Is Sequentially Diffusive and Directional. AB - The distribution and absorption of ingested protein was characterized within a colony of Podocoryna carnea when a single polyp was fed. Observations were conducted at multiple spatial and temporal scales at three different stages of colony ontogeny with an artificial food item containing Texas Red conjugated albumin. Food pellets were digested and all tracer absorbed by digestive cells within the first 2-3 hours post-feeding. The preponderance of the label was located in the fed polyp and in a transport-induced diffusion pattern surrounding the fed polyp. After 6 hours post-feeding particulates re-appeared in the gastrovascular system and their absorption increased the area over which the nutrients were distributed, albeit still in a pattern that was centered on the fed polyp. At later intervals, tracer became concentrated in some stolon tips, but not in others, despite the proximity of these stolons either to the fed polyp or to adjacent stolons receiving nutrients. Distribution and absorption of nutrients is sequentially diffusive and directional. PMID- 26359661 TI - DFT dissection of the reduction step in H2 catalytic production by [FeFe] hydrogenase-inspired models: can the bridging hydride become more reactive than the terminal isomer? AB - Density functional theory has been used to study diiron dithiolates [HFe2(xdt)(PR3)n(CO)5-nX] (n = 0, 2, 4; R = H, Me, Et; X = CH3S(-), PMe3, NHC = 1,3-dimethylimidazol-2-ylidene; xdt = adt, pdt; adt = azadithiolate; pdt = propanedithiolate). These species are related to the [FeFe]-hydrogenases catalyzing the 2H(+) + 2e(-) <-> H2 reaction. Our study is focused on the reduction step following protonation of the Fe2(SR)2 core. Fe(H)s detected in solution are terminal (t-H) and bridging (MU-H) hydrides. Although unstable versus MU-Hs, synthetic t-Hs feature milder reduction potentials than MU-Hs. Accordingly, attempts were previously made to hinder the isomerization of t-H to MU-H. Herein, we present another strategy: in place of preventing isomerization, MU-H could be made a stronger oxidant than t-H (E degrees MU-H > E degrees t-H). The nature and number of PR3 unusually affect DeltaE degrees t-H-MU-H: 4PEt3 models feature a MU-H with a milder E degrees than t-H, whereas the 4PMe3 analogues behave oppositely. The correlation DeltaE degrees t-H-MU-H <-> stereoelectronic features arises from the steric strain induced by bulky Et groups in 4PEt3 derivatives. One-electron reduction alleviates intramolecular repulsions only in MU-H species, which is reflected in the loss of bridging coordination. Conversely, in t-H, the strain is retained because a bridging CO holds together the Fe2 core. That implies that E degrees MU-H > E degrees t-H in 4-PEt3 species but not in 4PMe3 analogues. Also determinant to observe E degrees MU-H > E degrees t-H is the presence of a Fe apical sigma-donor because its replacement with a CO yields E degrees MU-H < E degrees t-H even in 4PEt3 species. Variants with neutral NHC and PMe3 in place of CH3S(-) still feature E degrees MU-H > E degrees t-H. Replacing pdt with (Hadt)(+) lowers E degrees but yields E degrees MU-H < E degrees t-H, indicating that MU-H activation can occur to the detriment of the overpotential increase. In conclusion, our results indicate that the electron richness of the Fe2 core influences DeltaE degrees t-H MU-H, provided that (i) the R size of PR3 must be greater than that of Me and (ii) an electron donor must be bound to Fe apically. PMID- 26359662 TI - Can the Results of Biodiversity-Ecosystem Productivity Studies Be Translated to Bioenergy Production? AB - Biodiversity experiments show that increases in plant diversity can lead to greater biomass production, and some researchers suggest that high diversity plantings should be used for bioenergy production. However, many methods used in past biodiversity experiments are impractical for bioenergy plantings. For example, biodiversity experiments often use intensive management such as hand weeding to maintain low diversity plantings and exclude unplanted species, but this would not be done for bioenergy plantings. Also, biodiversity experiments generally use high seeding densities that would be too expensive for bioenergy plantings. Here we report the effects of biodiversity on biomass production from two studies of more realistic bioenergy crop plantings in southern Michigan, USA. One study involved comparing production between switchgrass (Panicum virgatum) monocultures and species-rich prairie plantings on private farm fields that were managed similarly to bioenergy plantings. The other study was an experiment where switchgrass was planted in monoculture and in combination with increasingly species-rich native prairie mixtures. Overall, we found that bioenergy plantings with higher species richness did not produce more biomass than switchgrass monocultures. The lack of a positive relationship between planted species richness and production in our studies may be due to several factors. Non-planted species (weeds) were not removed from our studies and these non-planted species may have competed with planted species and also prevented realized species richness from equaling planted species richness. Also, we found that low seeding density of individual species limited the biomass production of these individual species. Production in future bioenergy plantings with high species richness may be increased by using a high density of inexpensive seed from switchgrass and other highly productive species, and future efforts to translate the results of biodiversity experiments to bioenergy plantings should consider the role of seeding density. PMID- 26359663 TI - Tea Consumption and Cognitive Impairment: A Cross-Sectional Study among Chinese Elderly. AB - BACKGROUND: Laboratorial and epidemiological researches suggested that tea exhibited potential neuroprotective effect which may prevent cognitive impairment, but there were few data among the elderly aged 60 years and above in China. OBJECTIVE: The objective was to explore the relationship between characteristics of tea consumption and cognitive impairment. DESIGN: We analyzed the baseline data from Zhejiang Major Public Health Surveillance Program (ZPHS) which was conducted in 2014. Totally 9,375 residents aged 60 years and above were recruited in this study. Face-to-face interview based on a self-developed questionnaire was performed for each participant. Detailed tea consumption habits were included in the questionnaire. Cognitive impairment screening was performed by using Mini-Mental State Examination (MMSE). Education-specific cut-off points for Chinese were applied to determine the status of cognitive impairment. Logistic regression analysis was used to calculate odds ratios (ORs) of cognitive impairment associated with tea consumption. RESULTS: The means (SD) of MMSE scores for the subjects who did not consume tea and consumed <2 cups/d, 2-4 cups/d, >=4 cups/d were 23.3 (SD = 5.61), 23.8 (SD = 5.60), 24.5 (SD = 5.63) and 25.0 (SD = 5.08), respectively. An inverse correlation was found between tea consumption (of all types) and prevalence of cognitive impairment. Volume of tea consumption was significantly associated with cognitive impairment: compared with non-consumption participants, those who consumed < 2 cups/d, 2-4 cups/d, and >=4 cups/d were observed ORs of 0.77 (95% CI: 0.56, 1.07), 0.62 (95% CI: 0.47, 0.81), and 0.49 (95% CI: 0.36, 0.66), respectively. Compared with non-consumption, black tea presented a positive correlation with cognitive function after controlling for potential confounders (OR = 0.52, 95% CI: 0.28, 0.95), while green tea showed no significant difference (OR = 1.04, 95% CI: 0.72, 1.51). Participants who consumed weak tea, moderate tea or strong tea more often were observed a better cognitive status when compared with those who did not have tea, with an OR of 0.51 (95% CI: 0.28, 0.92), 0.32 (95% CI: 0.19, 0.56) and 0.42 (95% CI: 0.22, 0.78) after adjusting for the potential confounders. But there was no statistically significant difference between any two of these ORs. CONCLUSION: Black tea consumption was association with better cognitive performance among the elderly aged 60 years and above in China, while green tea presented no correlation. The positive association of cognitive status with tea consumption was not limited to particular type of concentration. PMID- 26359664 TI - Transcriptome Sequencing, De Novo Assembly and Differential Gene Expression Analysis of the Early Development of Acipenser baeri. AB - The molecular mechanisms that drive the development of the endangered fossil fish species Acipenser baeri are difficult to study due to the lack of genomic data. Recent advances in sequencing technologies and the reducing cost of sequencing offer exclusive opportunities for exploring important molecular mechanisms underlying specific biological processes. This manuscript describes the large scale sequencing and analyses of mRNA from Acipenser baeri collected at five development time points using the Illumina Hiseq2000 platform. The sequencing reads were de novo assembled and clustered into 278167 unigenes, of which 57346 (20.62%) had 45837 known homologues proteins in Uniprot protein databases while 11509 proteins matched with at least one sequence of assembled unigenes. The remaining 79.38% of unigenes could stand for non-coding unigenes or unigenes specific to A. baeri. A number of 43062 unigenes were annotated into functional categories via Gene Ontology (GO) annotation whereas 29526 unigenes were associated with 329 pathways by mapping to KEGG database. Subsequently, 3479 differentially expressed genes were scanned within developmental stages and clustered into 50 gene expression profiles. Genes preferentially expressed at each stage were also identified. Through GO and KEGG pathway enrichment analysis, relevant physiological variations during the early development of A. baeri could be better cognized. Accordingly, the present study gives insights into the transcriptome profile of the early development of A. baeri, and the information contained in this large scale transcriptome will provide substantial references for A. baeri developmental biology and promote its aquaculture research. PMID- 26359665 TI - Effects of a Major Tree Invader on Urban Woodland Arthropods. AB - Biological invasions are a major threat to biodiversity; however, the degree of impact can vary depending on the ecosystem and taxa. Here, we test whether a top invader at a global scale, the tree Robinia pseudoacacia (black locust or false acacia), which is known to profoundly change site conditions, significantly affects urban animal diversity. As a first multi-taxon study of this kind, we analyzed the effects of Robinia dominance on 18 arthropod taxa by pairwise comparisons of woodlands in Berlin, Germany, that were dominated by R. pseudoacacia or the native pioneer tree Betula pendula. As a negative effect, abundances of five arthropod taxa decreased (Chilopoda, Formicidae, Diptera, Heteroptera, Hymenoptera); 13 others were not affected. Woodland type affected species composition of carabids and functional groups in spiders, but surprisingly did not decrease alpha and beta diversity of carabid and spider assemblages or the number of endangered species. Tree invasion thus did not induce biotic homogenization at the habitat scale. We detected no positive effects of alien dominance. Our results illustrate that invasions by a major tree invader can induce species turnover in ground-dwelling arthropods, but do not necessarily reduce arthropod species abundances or diversity and might thus contribute to the conservation of epigeal invertebrates in urban settings. Considering the context of invasion impacts thus helps to set priorities in managing biological invasions and can illustrate the potential of novel ecosystems to maintain urban biodiversity. PMID- 26359666 TI - Was the Risk from Nursing-Home Evacuation after the Fukushima Accident Higher than the Radiation Risk? AB - After the 2011 accident at the Fukushima Daiichi nuclear power plant, nursing home residents and staff were evacuated voluntarily from damaged areas to avoid radiation exposure. Unfortunately, the evacuation resulted in increased mortalities among nursing home residents. We assessed the risk trade-off between evacuation and radiation for 191 residents and 184 staff at three nursing homes by using the same detriment indicator, namely loss of life expectancy (LLE), under four scenarios, i.e. "rapid evacuation (in accordance with the actual situation; i.e. evacuation on 22 March)," "deliberate evacuation (i.e. evacuation on 20 June)," "20-mSv exposure," and "100-mSv exposure." The LLE from evacuation related mortality among nursing home residents was assessed with survival probability data from nursing homes in the city of Minamisoma and the city of Soma. The LLE from radiation mortality was calculated from the estimated age specific mortality rates from leukemia and all solid cancers based on the additional effective doses and the survival probabilities. The total LLE of residents due to evacuation-related risks in rapid evacuation was 11,000 persons d-much higher than the total LLEs of residents and staff due to radiation in the other scenarios (27, 1100, and 5800 persons-d for deliberate evacuation, 20 mSv exposure, and 100 mSv-exposure, respectively). The latitude for reducing evacuation risks among nursing home residents is surprisingly large. Evacuation regulation and planning should therefore be well balanced with the trade-offs against radiation risks. This is the first quantitative assessment of the risk trade-off between radiation exposure and evacuation after a nuclear power plant accident. PMID- 26359668 TI - Geographies of an Online Social Network. AB - How is online social media activity structured in the geographical space? Recent studies have shown that in spite of earlier visions about the "death of distance", physical proximity is still a major factor in social tie formation and maintenance in virtual social networks. Yet, it is unclear, what are the characteristics of the distance dependence in online social networks. In order to explore this issue the complete network of the former major Hungarian online social network is analyzed. We find that the distance dependence is weaker for the online social network ties than what was found earlier for phone communication networks. For a further analysis we introduced a coarser granularity: We identified the settlements with the nodes of a network and assigned two kinds of weights to the links between them. When the weights are proportional to the number of contacts we observed weakly formed, but spatially based modules resemble to the borders of macro-regions, the highest level of regional administration in the country. If the weights are defined relative to an uncorrelated null model, the next level of administrative regions, counties are reflected. PMID- 26359667 TI - Bioinformatics-Based Identification of MicroRNA-Regulated and Rheumatoid Arthritis-Associated Genes. AB - MicroRNAs (miRNAs) act as epigenetic markers and regulate the expression of their target genes, including those characterized as regulators in autoimmune diseases. Rheumatoid arthritis (RA) is one of the most common autoimmune diseases. The potential roles of miRNA-regulated genes in RA pathogenesis have greatly aroused the interest of clinicians and researchers in recent years. In the current study, RA-related miRNAs records were obtained from PubMed through conditional literature retrieval. After analyzing the selected records, miRNA targeted genes were predicted. We identified 14 RA-associated miRNAs, and their sub-analysis in 5 microarray or RNA sequencing (RNA-seq) datasets was performed. The microarray and RNA-seq data of RA were also downloaded from NCBI Gene Expression Omnibus (GEO) and Sequence Read Archive (SRA), analyzed, and annotated. Using a bioinformatics approach, we identified a series of differentially expressed genes (DEGs) by comparing studies on RA and the controls. The RA-related gene expression profile was thus obtained and the expression of miRNA-regulated genes was analyzed. After functional annotation analysis, we found GO molecular function (MF) terms significantly enriched in calcium ion binding (GO: 0005509). Moreover, some novel dysregulated target genes were identified in RA through integrated analysis of miRNA/mRNA expression. The result revealed that the expression of a number of genes, including ROR2, ABI3BP, SMOC2, etc., was not only affected by dysregulated miRNAs, but also altered in RA. Our findings indicate that there is a close association between negatively correlated mRNA/miRNA pairs and RA. These findings may be applied to identify genetic markers for RA diagnosis and treatment in the future. PMID- 26359670 TI - Extreme Expression of DNA Repair Protein Apurinic/Apyrimidinic Endonuclease 1 (APE1) in Human Breast Cancer As Measured by Liquid Chromatography and Isotope Dilution Tandem Mass Spectrometry. AB - Apurinic/apyrimidinic endonuclease 1 (APE1) is a DNA repair protein and plays other important roles. Increased levels of APE1 in cancer have been reported. However, available methods for measuring APE1 levels are indirect and not quantitative. We previously developed an approach using liquid chromatography and tandem mass spectrometry with isotope dilution to accurately measure APE1 levels. Here, we applied this methodology to measure APE1 levels in normal and cancerous human breast tissues. Extreme expression of APE1 in malignant tumors was observed, suggesting that breast cancer cells may require APE1 for survival. Accurate measurement of APE1 may be essential for the development of novel treatment strategies and APE1 inhibitors as anticancer drugs. PMID- 26359669 TI - Bovine CCL28 Mediates Chemotaxis via CCR10 and Demonstrates Direct Antimicrobial Activity against Mastitis Causing Bacteria. AB - In addition to the well characterized function of chemokines in mediating the homing and accumulation of leukocytes to tissues, some chemokines also exhibit potent antimicrobial activity. Little is known of the potential role of chemokines in bovine mammary gland health and disease. The chemokine CCL28 has previously been shown to play a key role in the homing and accumulation of IgA antibody secreting cells to the lactating murine mammary gland. CCL28 has also been shown to act as an antimicrobial peptide with activity demonstrated against a wide range of pathogens including bacteria, fungi and protozoans. Here we describe the cloning and function of bovine CCL28 and document the concentration of this chemokine in bovine milk. Bovine CCL28 was shown to mediate cellular chemotaxis via the CCR10 chemokine receptor and exhibited antimicrobial activity against a variety of bovine mastitis causing organisms. The concentration of bovine CCL28 in milk was found to be highly correlated with the lactation cycle. Highest concentrations of CCL28 were observed soon after parturition, with levels decreasing over time. These results suggest a potential role for CCL28 in the prevention/resolution of bovine mastitis. PMID- 26359671 TI - Nucleophilic Polymers and Gels in Hydrolytic Degradation of Chemical Warfare Agents. AB - Water- and solvent-soluble polymeric materials based on polyalkylamines modified with nucleophilic groups are introduced as catalysts of chemical warfare agent (CWA) hydrolysis. A comparative study conducted at constant pH and based on the criteria of the synthetic route simplicity, aqueous solubility, and rate of hydrolysis of CWA mimic, diisopropylfluorophosphate (DFP), indicated that 4 aminopyridine-substituted polyallylamine (PAAm-APy) and polyvinylamine substituted with 4-aminopyridine (PVAm-APy) were advantageous over 4 pyridinealdoxime-modified PVAm and PAAm, poly(butadiene-co-pyrrolidinopyridine), and PAAm modified with bipyridine and its complex with Cu(II). The synthesis of PVAm-APy and PAAm-APy involved generation of a betaine derivative of acrylamide and its covalent attachment onto the polyalkylamine chain followed by basic hydrolysis. Hydrogel particles of PAAm-APy and PVAm-APy cross-linked by epichlorohydrin exhibited pH-dependent swelling and ionization patterns that affected the rate constants of DFP nucleophilic hydrolysis. Deprotonation of the aminopyridine and amine groups increased the rates of the nucleophilic hydrolysis. The second-order rate of nucleophilic hydrolysis was 5.5- to 10-fold higher with the nucleophile-modified gels compared to those obtained by cross linking of unmodified PAAm, throughout the pH range. Testing of VX and soman (GD) was conducted in 2.5-3.7 wt % PVAm-APy suspensions or gels swollen in water or DMSO/water mixtures. The half-lives of GD in aqueous PVAm-APy were 12 and 770 min at pH 8.5 and 5, respectively. Addition of VX into 3.5-3.7 wt % suspensions of PVAm-APy in DMSO-d6 and D2O at initial VX concentration of 0.2 vol % resulted in 100% VX degradation in less than 20 min. The unmodified PVAm and PAAm were 2 orders of magnitude less active than PVAm-APy and PAAm-APy, with VX half-lives in the range of 24 h. Furthermore, the PVAm-APy and PAAm-APy gels facilitated the dehydrochlorination reaction of sulfur mustard (HD) and its analogue 2 chloroethyl ethylsulfide (CEES). The ability of the reported aminopyridine modified polyalkylamine materials to degrade the most persistent of CWAs, coupled with aqueous solubility, and the presence of numerous amino groups that provide convenient "handles" for covalent attachment on polymeric and inorganic supports yields promise for applications such as protective fabric and textile treatment and components of decontaminating materials. PMID- 26359672 TI - Comparison of three commercial fecal calprotectin ELISA test kits used in patients with Inflammatory Bowel Disease. AB - OBJECTIVE: Fecal calprotectin is a noninvasive marker of intestinal inflammation used to distinguish between functional and organic bowel diseases and to evaluate disease activity among patients with Inflammatory Bowel Disease (IBD). The goal of this study was to compare three different ELISA tests measuring calprotectin in their accuracy to detect IBD and to distinguish between IBD patients with active or inactive disease. MATERIAL AND METHODS: This study includes in total 148 fecal samples, 96 from patients with a previously confirmed IBD diagnosis and 52 from healthy controls, aged from 25 to 86 and 18 to 67 years, respectively. Disease activity in the patients was established using the following clinical activity indices: the Simple Clinical Colitis Activity Index (SCCAI), the Harvey Bradshaw Index (HBI) and the Modified Pouchitis Disease Activity Index (MPDAI). Three ELISA calprotectin tests (EK-CAL, CALPRO and HK325) were performed on fecal specimens and results compared. RESULTS: The CALPRO calprotectin ELISA test was shown to have the best specificity of 96% compared to the HK325 and the EK-CAL calprotectin ELISA tests with 28% specificity and 74% specificity, respectively. A significant correlation between clinical activity indices and fecal calprotectin was found in patients with ulcerative colitis (p < 0.05***) and in patients with an ileoanal pouch (p < 0.05), but not in patients with Crohn's disease (p = 0.11). CONCLUSION: The CALPRO ELISA test performed best in measuring calprotectin in feces. PMID- 26359673 TI - Treatment of boric acid overdose in two infants with Continuous Venovenous Hemodialysis. PMID- 26359674 TI - What is the risk of a shunt malfunction after elective intradural surgery? AB - OBJECT: Surgery for CSF diversion is the most common procedure performed by pediatric neurosurgeons. The failure rates for shunts remain frustratingly high, resulting in a burden to patients, families, providers, and healthcare systems. The goal of this study was to quantify the risk of a shunt malfunction in patients with an existing shunt who undergo an elective intradural operation. METHODS: All elective intradural surgeries (cranial and spinal) at Le Bonheur Children's Hospital from January 2010 through June 2014 were reviewed to identify those patients who had a functional ventricular shunt at the time of surgery. Patient records were reviewed to collect demographic, surgical, clinical, radiological, and pathologic data, including all details related to any subsequent shunt revision surgery. The primary outcome was all-cause shunt revision (i.e., malfunction or infection) within 90 days of elective intradural surgery. RESULTS: One hundred and fifty elective intradural surgeries were identified in 109 patients during the study period. There were 14 patients (12.8%, 13 male) who experienced 16 shunt malfunctions (10.7%) within 90 days of elective intradural surgery. These 14 patients underwent 13 craniotomies, 2 endoscopic fenestrations for loculated hydrocephalus, and 1 laminectomy for dorsal rhizotomy. Median time to failure was 9 days, with the shunts in half of our patients failing within 5 postoperative days. Those patients with failed shunts were younger (median 4.2 years [range 0.33-26 years] vs median 10 years [range 0.58-34 years]), had a shorter time interval from their previous shunt surgery (median 11 months [range 0-81 months] vs median 20 months [range 0-238 months]), and were more likely to have had intraventricular surgery (80.0% vs. 60.3%). CONCLUSIONS: This is the first study to quantify the risk of a shunt malfunction after elective intradural surgery. The 90-day all-cause shunt failure rate (per procedure) was 10.7%, with half of the failures occurring within the first 5 postoperative days. Possible risk factors for shunt malfunction after elective intradural surgeries are intraventricular surgical approach, shorter time since last shunt-related surgery, and young age. PMID- 26359676 TI - A person-oriented approach to hand hygiene behaviour: Emotional empathy fosters hand hygiene practice. AB - OBJECTIVES: Adopting a social-psychological approach, this research examines whether emotional empathy, an affective reaction regarding another's well-being, fosters hand hygiene as this affects other's health-related well-being extensively. DESIGN: Three studies tested this notion: (a) a cross-sectional study involving a sample of health care workers at a German hospital, (b) an experiment testing the causal effect of empathy on hand hygiene behaviour and (c) an 11-week prospective study testing whether an empathy induction affected disinfectant usage frequency in two different wards of a hospital. MAIN OUTCOME MEASURES: Self-reported hand hygiene behaviour based on day reconstruction method was measured in Study 1, actual hand sanitation behaviour was observed in Study 2 and disinfectant usage frequency in two different hospital wards was assessed in Study 3. RESULTS: Study 1 reveals an association of empathy with hand hygiene cross-sectionally, Study 2 documents the causal effect of empathy on increased hand sanitation. Study 3 shows an empathy induction increases hand sanitiser usage in the hospital. CONCLUSIONS: Increasing emotional empathy promotes hand hygiene behaviour, also in hospitals. Besides providing new impulses for the design of effective interventions, these findings bear theoretical significance as they document the explanatory power of empathy regarding a distal explanandum (hand hygiene). PMID- 26359675 TI - Inhibition of Diethylnitrosamine-Induced Hepatocarcinogenesis in Mice by a High Dietary Protein Intake. AB - Epidemiological and experimental evidence supports the key role of diet in the development of many types of cancer. Recent studies have suggested that dietary modifications may be beneficial for individuals at high risk for hepatocellular carcinoma (HCC). In this study, we investigated the effect of a high-protein (HP; 20% casein) dietondiethylnitrosamine (DEN)-induced hepatocarcinogenesis. Mice were given free access to water with 30 MUg/ml DEN and fed a normal or HP diet for 22 wk. The results showed mice consuming HP diets had reduced mortality rates and body weights and lower hepatic enzyme activity compared to DEN-treated mice on a normal diet. HP consumption also promoted collagen accumulation in the liver, and reduced numbers of proliferating hepatocytes and infiltrating inflammatory cells, as well as decreased expression of inflammatory factor interleukin-1beta, and nuclear factor kappaB activation. These data indicate that HP diets can inhibit DEN-induced hepatocarcinogenesis via suppression of the inflammatory response and provide a new evidence for the dietary management of clinical patients with hepatocellular carcinoma. PMID- 26359677 TI - Interactions between Polyelectrolyte Brushes and Hofmeister Ions: Chaotropes versus Kosmotropes. AB - We have investigated the interactions between the positively charged poly[2 (methacryloyloxy)ethyltrimethylammonium chloride] (PMETAC) brushes and the Hofmeister anions and the interactions between the negatively charged poly(3 sulfopropyl methacrylate potassium) (PSPMA) brushes and the Hofmeister cations using a combination of quartz crystal microbalance with dissipation and spectroscopic ellipsometry. A V-shaped anion series is observed in terms of the ion-specific interactions between the PMETAC brushes and the Hofmeister anions. We have found that the chaotropic and kosmotropic anions interact with the PMETAC brushes in different manners. The ion-specific interactions between the PMETAC brushes and the chaotropic anions are dominated by the direct interactions between the anions and the positively charged quaternary ammonium group via ion pairing mediated by ionic hydration strength or polarizability, whereas the ion specific interactions between the PMETAC brushes and the kosmotropic anions are dominated by the competition for water molecules between the anions and the brushes. The ion-specific interactions between the PMETAC brushes and the anions have significant influences on both the hydration and the conformation of the brushes. The cations exhibit weaker specific ion effects on the PSPMA brushes in comparison with the specific anion effects on the PMETAC brushes. PMID- 26359678 TI - The complete mitochondrial genome of red rainbowfish (Glossolepis incises Weber 1907). AB - In this study, the mitochondrial genome of Glossolepis incisus (Weber 1907 ) (Atheriniformes: Melanotaeniidae) was sequenced for the first time. The assembled mitogenome consisting of 16 529 bp, includes 13 protein-coding genes, 22 transfer RNAs, 2 ribosomal RNAs genes and 1 putative control region. The overall base composition of G. incisus is 27.51% for A, 30.04% for C, 16.06% for G, 26.39% for T and showS 91% identities to Lake Kutubu Rainbowfish, Melanotaenia lacustris. These data will provide useful molecular information for phylogenetic relationships within the family Melanotaeniidae species. PMID- 26359679 TI - Hospital housekeepers: Victims of ineffective hospital waste management. AB - Improper waste management exposes hospital housekeepers to biological risk. The objectives of this study were to identify the frequency and profile of exposure incidents, classify the role of sharps waste, and compare the first and last occurrences for hospital housekeepers with multiple exposure incidents. A retrospective epidemiological study using Brazilian records from 1989 to 2012 was conducted. Data analyzed included hospital treatment records and the state notification database. Probabilistic linkage was performed using LinkPlus and data analysis using SPSS. There were 996 (11.6%) injuries, with 57 (6.1%) workers reporting multiple occurrences, for a total of 938 workers. These were primarily needlestick injuries (98.5%), involving blood (85.6%), caused by hypodermic needles (75.1%), and improper sharps disposal (70.8%). The number of workers completing vaccination after their first injury and before their last injury was statistically significant. Additional efforts to prevent and manage exposure incidents are needed. PMID- 26359681 TI - Microwave Spectrum for a Second Higher Energy Conformer of Cyclopropanecarboxylic Acid and Determination of the Gas Phase Structure of the Ground State. AB - Microwave spectra for a higher-energy conformer of cyclopropanecarboxylic acid (CPCA) were measured using a Flygare-Balle-type pulsed-beam Fourier transform microwave spectrometer. The rotational constants (in megahertz) and centrifugal distortion constants (in kilohertz) for this higher-energy conformer are A = 7452.3132(57), B = 2789.8602(43), C = 2415.0725(40), DJ = 0.29(53), and DJK = 2.5(12). Differences between rotational constants for this excited-state conformation and the ground state are primarily due to the acidic OH bond moving from a position cis relative to the cyclopropyl group about the C1-C9 bond to the more stable trans conformation. Calculations indicate that the relative abundance of the higher-energy state should be 15% to 17% at room temperature, but the observed relative abundance for the supersonic expansion conditions is about 1%. The measurements of rotational transitions for the trans form of CPCA were extended to include all of the unique (13)C singly substituted positions. These measurements, along with previously measured transitions of the parent and -OD isotopologues, were used to determine a best-fit gas-phase structure. PMID- 26359680 TI - Discovery of ((4-(5-(Cyclopropylcarbamoyl)-2-methylphenylamino)-5 methylpyrrolo[1,2-f][1,2,4]triazine-6-carbonyl)(propyl)carbamoyloxy)methyl-2-(4 (phosphonooxy)phenyl)acetate (BMS-751324), a Clinical Prodrug of p38alpha MAP Kinase Inhibitor. AB - In search for prodrugs to address the issue of pH-dependent solubility and exposure associated with 1 (BMS-582949), a previously disclosed phase II clinical p38alpha MAP kinase inhibitor, a structurally novel clinical prodrug, 2 (BMS 751324), featuring a carbamoylmethylene linked promoiety containing hydroxyphenyl acetic acid (HPA) derived ester and phosphate functionalities, was identified. Prodrug 2 was not only stable but also water-soluble under both acidic and neutral conditions. It was effectively bioconverted into parent drug 1 in vivo by alkaline phosphatase and esterase in a stepwise manner, providing higher exposure of 1 compared to its direct administration, especially within higher dose ranges. In a rat LPS-induced TNFalpha pharmacodynamic model and a rat adjuvant arthritis model, 2 demonstrated similar efficacy to 1. Most importantly, it was shown in clinical studies that prodrug 2 was indeed effective in addressing the pH dependent absorption issue associated with 1. PMID- 26359682 TI - Preliminary comparative study of two accelerometers performances for evaluation of dorsoventral movement in trotting horse. PMID- 26359683 TI - Mobile AMPARs are required for synaptic plasticity. PMID- 26359684 TI - Isolation and Functional Characterization of Carotenoid Cleavage Dioxygenase-1 from Laurus nobilis L. (Bay Laurel) Fruits. AB - Bay laurel (Laurus nobilis L.) is an agriculturally important tree used in food, drugs, and the cosmetics industry. Many of the health beneficial properties of bay laurel are due to volatile terpene metabolites that they contain, including various norisoprenoids. Despite their importance, little is known about the norisoprenoid biosynthesis in Laurus nobilis fruits. We found that the volatile norisoprenoids 6-methyl-5-hepten-2-one, pseudoionone, and beta-ionone accumulated in Laurus nobilis fruits in a pattern reflecting their carotenoid content. A full length cDNA encoding a potential carotenoid cleavage dioxygenase (LnCCD1) was isolated. The LnCCD1 gene was overexpressed in Escherichia coli, and recombinant protein was assayed for its cleavage activity with an array of carotenoid substrates. The LnCCD1 protein was able to cleave a variety of carotenoids at the 9,10 (9',10') and 5,6 (5',6') positions to produce 6-methyl-5-hepten-2-one, pseudoionone, beta-ionone, and alpha-ionone. Our results suggest a role for LnCCD1 in Laurus nobilis fruit flavor biosynthesis. PMID- 26359685 TI - Maternal IgG Anti-A and Anti-B Titer Levels Screening in Predicting ABO Hemolytic Disease of the Newborn: A Meta-Analysis. AB - Maternal IgG anti-A/B titers have been considered as a susceptible factor to the risk of ABO hemolytic disease in newborn (ABO-HDN). However, the results remain controversial. This meta-analysis aimed to estimate the association between maternal IgG anti-A/B titers and the risk of ABO-HDN. METHODS: Trials on the relationship between maternal IgG anti-A/B titers and the risk of ABO-HDN were collected by searching Embase, PubMed, and Cochrane Central Register of Controlled Trials (CENTRAL) electronic databases. The inclusion criteria were maternal IgG anti-A/B titers screening and the evaluation of clinical outcomes in relation to ABO-HDN. Stata 12.0 was used to analyze the data. RESULTS: A total of 23 trials were eligible for inclusion, of which four trials with 5,246 participants were suitable for this meta-analysis. Meta-analysis results suggested that maternal IgG anti-A/B titers were significantly associated with the risk of ABO-HDN [OR = 2.86, 95% CI = 2.50-3.28; OR = 4.67, 95% CI = 3.92 5.55; OR = 1.61, 95% CI = 1.36-1.91 in titers (128 to 256) vs. titers (64 or lower), titers (512 or higher) vs. titers (64 or lower), and titers (512 or higher) vs. titers (128-256), respectively]. CONCLUSIONS: Our meta-analysis suggests that maternal IgG anti-A/B titers are significantly associated with the risk of ABO-HDN. They contribute to the prediction of risk of ABO-HDN, in addition to the need for invasive treatment for antibody titers >=512. PMID- 26359686 TI - The effects of lycopene on intestinal injury due to methotrexate in rats. AB - OBJECTIVE: The aim of this study was to investigate the effects of lycopene (Lyc) on methotrexate (Mtx)-induced intestinal damage in rats. METHOD: Twenty-eight male Sprague Dawley rats were divided into four equal groups: control, Mtx, Lyc, and Mtx-L. CONTROL GROUP: Rats were given only the vehicle. Lyc group: Rats were given Lyc (10 mg/kg) with corn oil by oral gavage for 10 days. Mtx group: Rats were injected intraperitoneally with a single dose of 20 mg/kg of Mtx and given corn oil by oral gavage. Mtx-L group: Rats were treated with Lyc (10 mg/kg) for 10 days after a single dose of Mtx (20 mg/kg). All of the rats were euthanized using terminal anesthesia, and the intestinal tissues were removed for histological examination and for pro-inflammatory cytokine measurement (tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1beta)), total oxidative status (TOS), total antioxidant capacity (TAC), and oxidative stress index (OSI). RESULTS: Mtx administration increased histopathological damage and increased TNF-alpha, IL-1beta, TOS, TAC, and OSI levels in the small intestine tissues. Lyc therapy applied to the Mtx-L group provided significant improvement in all parameters of histopathological damage to the small intestine and significantly reduced the levels of IL-1beta, TOS, and OSI in the intestinal tissues. CONCLUSIONS: The results of this study indicate that Lyc might be useful for protecting intestinal damage induced by Mtx in rats by reducing the increased oxidative stress and pro-inflammatory cytokine (IL-1beta) levels. PMID- 26359687 TI - [4 + 3] Cycloadditions with Bromo-Substituted Morita-Baylis-Hillman Adducts of Isatins and N-(ortho-Chloromethyl)aryl Amides. AB - Efficient construction of a challenging aza-spirocycloheptane oxindole scaffold is reported through an unprecedented [4 + 3] cycloaddition reaction with bromo substituted Morita-Baylis-Hillman adducts of isatins and N-(ortho chloromethyl)aryl amides. Both reactive intermediates, the allylic phosphonium ylides and aza-o-quinone methides, were in situ generated, chemoselectively facilitated by a Lewis base and Bronsted base, respectively. PMID- 26359688 TI - Prenatal Brain Imaging in Isolated vs. Complicated Club Foot: A Cohort Study. AB - Purpose: Talipes equinovarus (TEV) is a common birth defect. Differentiation between isolated and complex TEV is fundamental due to its effect on prognosis. Association between TEV and poor neurological outcome is more prominent in complex cases and highlights the significance of brain evaluation. The aim of the current study was to evaluate the contribution of fetal brain MRI to sonographic evaluation. Materials and Methods: In this retrospective study we evaluated charts of all pregnant patients referred for fetal brain MRI due to fetal TEV between 1/1/2011 and 12/31/14 in a single tertiary referral center. Isolated and complex TEV were differentiated according to associated anomalies. Brain US and MRI results were compared. Results: 28 pregnant patients were included with an average gestation and parity of 2.5 and 1.5, respectively. Both isolated and complicated TEV groups included 14 fetuses after initial TEV diagnosis on anatomical survey. Brain sonography and MRI were normal among 12/14 patients with isolated TEV while two patients were later diagnosed with mild ventriculomegaly. US brain evaluation has revealed pathologic findings in 4 (28.6 %) cases in the complicated TEV group, while MRI demonstrated abnormal findings in 8 (57.1 %) fetuses with notable severity diversity. In 6 cases, MRI diagnosed additional pathologies which were not demonstrated by US. Conclusion: Brain fetal MRI is an efficient tool during antenatal evaluation of complicated TEV with a high percentage of additional findings not demonstrated songraphically while its efficacy in isolated cases is in doubt. The current study expands the relevance of fetal brain MRI in cases of non-CNS anomalies. PMID- 26359689 TI - Detecting Lymphedema: Bioimpedance Spectroscopy and the Tissue Dielectric Constant. PMID- 26359692 TI - Di-(2-ethylhexyl) adipate and 20 phthalates in composite food samples from the 2013 Canadian Total Diet Study. AB - A sensitive and selective GC-MS method was developed and used for simultaneous analysis of di-(2-ethylhexyl) adipate (DEHA) and 20 selected phthalates in the food samples from the 2013 Canadian Total Diet Study. At least one of the 21 target chemicals was detected in 141 of the 159 different food composite samples analysed. However, only seven of the 21 target chemicals were detected, with di (2-ethylhexyl) phthalate (DEHP) and DEHA being detected most frequently, in 111 and 91 different food composite samples, respectively, followed by di-n-butyl phthalate (DBP) (n = 44), n-butyl benzyl phthalate (BBzP) (32), di-iso-butyl phthalate (DiBP) (27), di-ethyl phthalate (DEP) (3), and di-cyclohexyl phthalate (DCHP) (1). Levels of DEP (di-ethyl phthalate), DiBP, DBP, BBzP and DCHP were low, in general, with average concentrations of 9.63, 8.26, 23.2, 12.4 and 64.9 ng g(-1), respectively. Levels of DEHA and DEHP varied widely, ranging from 1.4 to 6010 ng g(-1) and from 14.4 to 714 ng g(-1), respectively. High levels of DEHA were found mainly in the composite samples where the individual food items used to prepare the composite were likely packaged in polyvinyl chloride (PVC) wrapping film, while the highest DEHP levels were found in the vegetable and fruit samples. PMID- 26359693 TI - Efficient electrocatalytic CO2 reduction with a molecular cofacial iron porphyrin dimer. AB - A cofacial iron tetraphenyl porphyrin dimer, , bio-inspired by the Ni-Fe containing metalloenzyme, carbon monoxide dehydrogenase (CODH), efficiently and selectively catalyses the electrochemical reduction of CO2 to CO in DMF/10% H2O solution at the electro-generated Fe(0)(por) species with high Faradic efficiency (95%) and TOF (4300 s(-1)) at a moderate overpotential, eta = 0.66 V. PMID- 26359695 TI - FlavonQ: an automated data processing tool for profiling flavone and flavonol glycosides with ultra-high-performance liquid chromatography-diode array detection-high resolution accurate mass-mass spectrometry. AB - Profiling flavonoids in natural products poses a great challenge due to the diversity of flavonoids, the lack of commercially available standards, and the complexity of plant matrixes. The increasingly popular use of ultra-high performance liquid chromatography-diode array detection-high resolution accurate mass-mass spectrometry (UHPLC-HRAM-MS) for the analysis of flavonoids has provided more definitive information but also vastly increased amounts of data. Thus, mining of the UHPLC-HRAM-MS data is a very daunting, labor-intensive, and expertise-dependent process. An automated data processing tool, FlavonQ, was developed that can transfer field-acquired expertise into data analysis and facilitate flavonoid research. FlavonQ is an "expert system" designed for automated data analysis of flavone and flavonol glycosides, two important subclasses of flavonoids. FlavonQ is capable of data format conversion, peak detection, flavone and flavonol glycoside peak extraction, flavone and flavonol glycoside identification, and production of quantitative results. An expert system was applied to the determination of flavone and flavonol glycosides in nine different plants with an average execution time of less than 1 min. The results obtained by FlavonQ were in good agreement with those determined conventionally by a flavonoid expert. PMID- 26359696 TI - Brain Metastases at Presentation in Patients With Non-Small Cell Lung Cancer. AB - OBJECTIVE: We used brain radiotherapy as a surrogate for the presence of brain metastases in patients with non-small cell lung cancer (NSCLC) to determine the prevalence of brain metastases using the Surveillance Epidemiology and End Results database. METHODS: Patients with NSCLC diagnosed between 1988 and 1997 were subdivided according to brain radiotherapy status at presentation into: "none" or "radiation therapy indicated." We calculated the frequency of brain radiotherapy use in all patients. Odds ratios (ORs) for the indication of brain radiotherapy were calculated for individual prespecified covariates of interest. All statistical tests were 2-sided and P<0.05 were considered significant. RESULTS: At presentation, brain radiotherapy was indicated in 10,963 (8.3%) of the 131,456 patients diagnosed with NSCLC between 1988 and 1997. On multivariable analysis the following were significantly associated with brain radiotherapy use: age (OR, 0.653 per 10 y increase in age; 95% confidence interval [CI]: 0.642, 0.665); female sex (OR, 1.05; 95% CI: 1.01, 1.10]); adenocarcinoma histology (HR, 1.67; 95% CI: 1.58, 1.76) or large cell or other histology (OR, 1.67; 95% CI: 1.57, 1.77); tumor size>3 cm (3.1 to 5 cm OR, 1.22; 95% CI: 1.14, 1.30 and >5 cm OR, 1.25; 95% CI: 1.17, 1.33); tumor grade >II (grade III OR, 1.82; 95% CI: 1.69, 1.95 and grade IV OR, 1.91; 95% CI: 1.73, 2.11); and nodal involvement N1 (OR, 1.33; 95% CI: 1.20, 1.47), N2 (OR, 2.24; 95% CI: 2.10, 2.40), and N3 (OR, 2.39; 95% CI: 2.19, 2.60). CONCLUSIONS: Brain radiotherapy is indicated in over 8% of patients with NSCLC at presentation. We demonstrated that the risk of brain metastasis at presentation may be stratified with the use of 6 clinical factors. PMID- 26359697 TI - Patterns of Long-term Cancer Survivorship Care in a National Cancer Institute Designated Comprehensive Cancer Center. AB - PURPOSE: The majority of the cancer survivors in the United States are 5 or more years beyond their diagnosis. The follow-up care of these individuals remains a major concern for survivors and for the cancer care system. The purpose of this study was to characterize long-term cancer survivors' visits at a National Cancer Institute-designated comprehensive cancer center. MATERIALS AND METHODS: We abstracted electronic medical record data for 18,882 unique patients' visits during 2010 to determine the distribution of the number of years of survival after the initial cancer diagnosis. We then reviewed 374 patient visits during a randomly selected week in April 2010 to determine whether patients were seen for treatment of a new diagnosis of cancer, a residual or recurrent cancer, for a second or secondary cancer, or for cancer survivorship care while not actively receiving treatment (other than adjuvant hormonal therapy). RESULTS: In the 1 year group of 18,882 unique patients visits the percentage of patients who were <1, 1 to 5, 6 to 10, and >10 years postdiagnosis were 18.7%, 48.7%, 18.9%, and 13.8%, respectively. During the selected week, 74% of the total office visits were with patients who were being actively treated for a new cancer, relapse, or a second cancer, whereas 24% were not being seen for treatment of an active malignancy. The percentage of total office visits with patients who were <6, 6 to 10, or >10 years postdiagnosis and had completed their initial treatment were 21.4%, 3.7%, and 1%, respectively. Approximately 5% of oncology office visits were with cancer survivors who were 5 or more years postdiagnosis and not receiving treatment. CONCLUSIONS: In a database of over 18,000 unique patients who were seen at a major cancer center in 2010, approximately 68% were 5 or less and 32% were 6 or more years postdiagnosis. A review of the medical oncology notes in a random sample of cases of oncology visits demonstrated that approximately 5% of office visits were with long-term cancer survivors who were >5 years postdiagnosis and not receiving active treatment. IMPLICATIONS FOR CANCER SURVIVORS: Cancer survivors often indicate a preference to receive long term follow-up care from their oncologist. These findings suggest that long-term cancer survivorship care represents only a small component of care at a comprehensive cancer center and also that alternative models for long-term survivorship health care need to be considered. PMID- 26359694 TI - Enhanced cell migration and apoptosis resistance may underlie the association between high SERPINE1 expression and poor outcome in head and neck carcinoma patients. AB - High SERPINE1 expression is a common event in head and neck squamous cell carcinoma (HNSCC); however, whether it plays a role in determining clinical outcome remains still unknown. We studied SERPINE1 as a prognostic marker in two HNSCC patient cohorts. In a retrospective study (n = 80), high expression of SERPINE1 was associated with poor progression-free (p = 0.022) and cancer specific (p = 0.040) survival. In a prospective study (n = 190), high SERPINE1 expression was associated with poor local recurrence-free (p = 0.022), progression-free (p = 0.002) and cancer-specific (p = 0.006) survival. SERPINE1 expression was identified as an independent risk factor for progression-free survival in patients treated with chemo-radiotherapy or radiotherapy (p = 0.043). In both patient cohorts, high SERPINE1 expression increased the risk of metastasis spread (p = 0.045; p = 0.029). The association between SERPINE1 expression and survival was confirmed using the HNSCC cohort included in The Cancer Genome Atlas project (n = 507). Once again, patients showing high expression had a poorer survival (p < 0.001). SERPINE1 over-expression in HNSCC cells reduced cell proliferation and enhanced migration. It also protected cells from cisplatin-induced apoptosis, which was accompanied by PI3K/AKT pathway activation. Downregulation of SERPINE1 expression had the opposite effect. We propose SERPINE1 expression as a prognostic marker that could be used to stratify HNSCC patients according to their risk of recurrence. PMID- 26359698 TI - Langerhans Cell Histiocytosis Presenting as a Nodulo-Ulcerative Eyelid Lesion. AB - The authors describe a 23-year-old man with unilateral upper eyelid swelling that evolved into a multinodular lesion with central necrosis, mimicking a neoplasm. Biopsy showed a lympho-histiocytic, eosinophil-rich proliferation with positivity for Langerhans cell markers CD1a and S-100 and histiocytic marker CD68. A literature review disclosed 11 documented cases of Langerhans cell histiocytosis of the eyelid with variable clinical presentations. This rare eyelid lesion, nearly always solitary, has no clinically distinctive characteristics and requires biopsy for diagnosis. Langerhans cell histiocytosis (LCH), formerly histiocytosis X, comprises a group of rare disorders characterized by the proliferation of specialized bone marrow-derived Langerhans cells intermingled with mature eosinophils. Proliferations may be multifocal (disseminated) or unifocal (solitary). Ophthalmic lesions are usually unifocal and tend to be located in the orbital region. Isolated eyelid foci are rare and present with variable patterns that preclude clinical diagnosis. In this report, the authors describe a case of multinodular, ulcerative involvement of the eyelid skin that mimicked a basal cell carcinoma. This study was conducted in compliance with the rules and regulations of the Health Insurance Portability and Accountability Act. PMID- 26359699 TI - Eyelid Contour Following Conjunctival Mullerectomy With or Without Tarsectomy Blepharoptosis Repair. AB - PURPOSE: To quantitatively determine how accurately conjunctival Mullerectomy with or without tarsectomy (CM +/- T) blepharoptosis repair restores eyelid contour. METHODS: The charts of all patients undergoing unilateral CM +/- T blepharoptosis repair at the Cole Eye Institute between June 2012 and September 2014 were reviewed. Preoperative and postoperative digital images were used for eyelid contour analysis. Eyelid contour was measured according to a previously described technique measuring 13 radial mid-pupil eyelid distances (MPLDs) in pixels at 15 degrees intervals from 0 degrees to 180 degrees . Eyelid contour was computed taking the ratio of the corresponding radial MPLD on either side of margin reflex distance (105/75, 120/60, 135/45, 150/30, 165/15, and 180/0) using ImageJ software (National Institutes of Health, Bethesda, MD). Ratios were compared between the preoperative and postoperative images using paired t test with statistical significance set at p < 0.05. RESULTS: One hundred and six cases of unilateral CM +/- T were performed during the study period and 20 cases met inclusion criteria. In the ptotic eyelid, the postoperative eyelid and the unoperated eyelid groups, the average temporal-to-nasal MPLD ratios at corresponding angles from the midline were closer to 1 from 45 degrees to 135 degrees . Then, further from the midline, at more obtuse angles, the temporal MPLD was greater than the nasal MPLD (i.e., the ratio was greater than 1) in all 3 groups. CONCLUSIONS: There was no significant difference in any corresponding MPLD or temporal/nasal MPLD ratio between the postoperative eyelid and the postoperative control eyelid. This technique for CM +/- T blepharoptosis repair adequately restores eyelid contour. PMID- 26359700 TI - The Locking Y Lateral Canthopexy With Osseous Integration: Clinical Experience and Surgical Technique. AB - PURPOSE: To describe a surgical technique to correct lateral canthal tendon disinsertion with a strabismus surgery-inspired locking capture of the tendon complex and osseous integration via drill holes. METHODS: Retrospective interventional case series including all patients with lateral canthal tendon disinsertion who underwent locking Y lateral canthopexy with drill hole reinforcement by 1 surgeon (D.T.T.) between 2006 and 2011. Outcome measures included resolution of presenting ocular symptoms, improved blink dynamics and lid closure, correction of lagophthalmos and exposure keratopathy, and need for further surgery. RESULTS: A total of 53 lateral canthopexies with osseous integration were performed in 42 patients who fulfilled clinical criteria for lateral canthal tendon disinsertion. The population was biased toward treatment failures; 81% of eyes (43/53) had a history of prior lateral canthal tightening, and of these 30.2% (16/53) had undergone 3 or more procedures. Postoperatively, all eyes demonstrated improved eyelid position and blink mechanics, and 83% (44/53) had subjective resolution of epiphora and ocular irritation. Lagophthalmos was fully corrected in 95% (19/20) of cases, and corneal staining resolved in 88% (14/16). With a mean follow-up period of 24 months, 3.7% of eyes (2/53) required additional lateral canthal tightening. CONCLUSIONS: The locking Y lateral canthopexy is an effective and durable method for repositioning the lateral canthal tendon complex to improve blink dynamics, eyelid closure, and cosmesis. Even in a population heavily biased toward treatment failure, clinical results are excellent and the reoperation rate is low. PMID- 26359701 TI - Conjunctiva-Sparing Posterior Ptosis Surgery: A Novel Approach. AB - PURPOSE: Muller's muscle conjunctiva resection is a well-established means of correcting blepharoptosis. The primary objective of this prospective study was to determine if modifying Muller's muscle conjunctiva resection by sparing the conjunctiva would accomplish successful repair while allowing patients to retain their conjunctiva. The potential advantages of preserving conjunctiva are significant and include: conservation of an anatomically normal tissue, retention of goblet cells, reduction of suture-related complications such as corneal irritation or abrasion as the conjunctiva covers the suture during postoperative healing, and preservation of conjunctiva for potential future surgical procedures critical to ocular health. METHODS: This is a prospective study enrolling patients with mild to moderate ptosis. RESULTS: The procedure has been performed in 18 patients and 30 eyelids. Follow up at 1 week revealed normal healing with expected postoperative edema and ecchymosis. Notably, all patients were free of any corneal abrasion or irritation. Follow up at 1 month and a minimum of 3 months (average 5.7 months) revealed that all patients had satisfactory correction of their blepharoptosis with Margin Reflex Distance 1 (MRD1) improvement to within 1 mm of the anticipated goal, preserved eyelid margin contour, and good symmetry (average 0.26 mm difference in MRD1 between the sides). CONCLUSION: These results show an effective correction of blepharoptosis with a favorable cosmetic outcome and low postoperative complication rate; all while preserving the conjunctiva. PMID- 26359702 TI - IgG4 Staining in Thyroid Eye Disease. AB - IgG4-related ophthalmic disease is increasingly widely recognized. Moreover, IgG4 staining can occur in other inflammatory diseases. The authors report a case of IgG4 staining of an enlarged, inflamed levator palpebrae superioris in a patient with a past history of thyroid eye disease. A 78-year-old woman with quiescent hyperthyroidism had clinical and radiological evidence of levator palpebrae superioris inflammation without superior rectus involvement. A biopsy was consistent with IgG4-related ophthalmic disease. There was a marked but incomplete response to an orbital injection of triamcinolone. The authors discuss the association between thyroid eye disease and IgG4 staining and the diagnostic issues that arise when IgG4-related ophthalmic disease criteria are fulfilled in patients with other orbital inflammatory conditions. PMID- 26359703 TI - Application of Computer Techniques in Correcting Mild Zygomatic Assymetry With Unilateral Reduction Malarplasty. AB - Zygomatic assymetry is common in the population, which often requires surgical correction for aesthetic concerns. Previously, surgeons performed the surgery often based on their personal experience and visual evaluation. The purpose of this study was to apply computer techniques in patients with mild zygomatic asymmetry treated with unilateral reduction malarplasty to improve surgical accuracy and reduce preoperative risks. The authors used computer techniques to plan osteotomies, to produce surgical template, and to evaluate the surgical outcome. Postoperative follow-up demonstrated that zygomatic asymmetry was corrected in all the patients without complications. The proposed methodology was considered to be helpful in improving the surgical accuracy and efficiency for treatment of zygomatic asymmetry, while greatly minimizing operative risk. PMID- 26359704 TI - Simplified Designing and Insetting of the Free Flap in Reconstructing Oral and/or Oropharyngeal Defect. AB - Reconstructing oral and/or oropharyngeal defect after tumor ablation requires anatomic restoration of the complex structures to maximize functional outcomes. This study introduces a simple and adjustable way of designing and insetting of a free flap in such reconstruction. Patients who received free flap reconstruction of oral and/or oropharyngeal defect with 33% to 66% of the native tongue left intact after resection of the tumor were enrolled and reviewed. Flap was designed as an oval shape according to the maximum width and length of the defect, and sutured from the most posterior part. Natural imbrication of the flap formed by anterior pulling of the tongue was marked and de-epithelized to create a three dimensional shape. A total of 30 patients met the inclusion criteria of this study and the median follow-up was 32 months. All flaps survived after 1 case of venous reanastomosis. The average hospital stay was 23.7 days. All patients were decannulated. Twenty (66.7%) patients could eat a normal or soft diet, and 19 (63.3%) patients had normal or intelligible speech. Simplified designing of the flap with adjustable tailoring allowed for easy and effective way of free flap oral and/or oropharyngeal reconstruction. De-epithelization (or trimming) of the naturally imbricated area during the procedure of insetting created a bilobed shape in effect to conform to the three-dimensional defect. PMID- 26359705 TI - Near-Total Pediatric Parotidectomy for Refractory Chronic Sialadenitis. PMID- 26359706 TI - Julius Sachs (1832-1897) and the Unity of Life. AB - In 1865, the German botanist Julius Sachs published a seminal monograph entitled Experimental-Physiologie der Pflanzen (Experimental Physiology of Plants) and hence became the founder of a new scientific discipline that originated 150 y ago. Here, we outline the significance of the achievements of Sachs. In addition, we document, with reference to his Vorlesungen uber Pflanzen-Physiologie (Lectures on the Physiology of Plants, 1882), that Sachs was one of the first experimentalists who proposed the functional unity of all organisms alive today (humans, animals, plants and other "vegetable" organisms, such as algae, cyanophyceae, fungi, myxomycetes, and bacteria). PMID- 26359707 TI - Diagnostic yield and complications of extended lymphadenectomy versus limited lymphadenectomy combined with radical prostatectomy. AB - BACKGROUND: Lymphadenectomy for prostate cancer (PC) is the most reliable procedure for detecting lymphatic metastases. The optimal extension of this procedure is still a topic of debate. OBJECTIVE: To analyse the diagnostic performance and complications of extended lymphadenectomy (ELD) and limited lymphadenectomy (LLD) in a series of patients with high-risk PC who underwent radical prostatectomy (RP). MATERIAL AND METHODS: A retrospective study was conducted on patients with high d'Amico risk who underwent RP with lymphadenectomy between 1999 and 2014. A comparative analysis was performed of the diagnostic capacity of lymphatic metastases of ELD and LLD and of postoperative complications at 90 days. RESULTS: Ninety-three patients were analysed, 20 (21.5%) and 73 (78.5%) of whom underwent ELD and LLD, respectively. The mean age of the series was 65.26 years (SD, 5.51). The median follow-up was 1.51 (0.61-2.29) years in the ELD group and 5.94 (3.61-9.10) in the LLD group. The median number of nodes obtained was 13 (9-23) in the ELD group compared with 5 (2-8) in the LLD group (p <.001). The percentages of patients with positive nodes in the ELD and LLD groups were 35% and 5.47%, respectively (p <.001). The overall complication rate at 90 days was 35.5% (33 patients). In the ELD group, 12 patients (60%) had complications, compared with 21 patients (28.8%) in the LLD group (p=.016), with no significant differences in severity according to the Clavien scale (p=.73). CONCLUSIONS: In our series, the detection of metastatic nodes was significantly greater with ELD. ELD increases the number of complications, with no differences compared with LLD in severity according to the modified Clavien scale. PMID- 26359708 TI - Incremental prognostic value of coronary computed tomographic angiography high risk plaque characteristics in newly symptomatic patients. AB - BACKGROUND: The incremental prognostic value of the plaque features in coronary computed tomographic angiography (CTA) has not been well assessed. This study was designed to determine whether CTA high-risk plaques have prognostic value incremental to the Framingham risk score (FRS) and the severity of luminal obstruction. METHODS: A total of 628 newly symptomatic patients without known coronary artery disease underwent CTA. They were followed for a median of 677 days during which there were 26 cardiac events, including cardiac death, acute myocardial infarction, and hospitalization for unstable angina. Incremental prognostic value of adding plaque characteristics to the number of diseased vessels and the FRS was evaluated using 3 Cox models and net reclassification indexes. RESULTS: The discrimination index was significantly increased by adding the number of diseased vessels to the FRS (change in c-statistic from 65.8% to 78.6%, p=0.028) but not significantly by further adding plaque characteristics (change in c-statistic from 78.6% to 80.0%, p=0.812). However, improved model fitting by adding plaque characteristics into the linear combination with risk score and the number of diseased vessels (p=0.007 from likelihood ratio test) and the lowest value of Akaike's information criteria of that model indicated that plaque characteristics improved both predictive accuracy and discrimination perspective. More subjects reclassified by plaque characteristics were moved to directions consistent with their subsequent cardiac event status than in an inconsistent direction. CONCLUSIONS: Evaluation of CTA plaque characteristics may provide incremental prognostic value to the number of diseased vessels and the FRS. PMID- 26359709 TI - Late cardiac morbidity of adjuvant radiotherapy for early breast cancer - A population-based study. AB - PURPOSE: The purpose of this study was to assess the long-term cardiac morbidity and mortality after breast irradiation using contemporary irradiation techniques. METHODS: We used the Catastrophic Illness dataset from the National Health Insurance Research Database to explore the possible association between late cardiotoxicity and women with early breast cancer treated with breast conservation therapy from 2000 to 2010. The Cox proportional-hazards model was used to compare breast cancer patients who received adjuvant radiotherapy versus without adjuvant radiotherapy for the end points with the following primary diagnoses (International Classification of Diseases, 9th Revision codes): ischemic heart disease (410-414, 36.0, 36.1), valvular heart disease (394-397, 424, 35), congestive heart failure (428, 402.01, 402.11, 402.91), and conduction abnormalities (426, 37.7-37.8, 37.94-37.99). RESULTS: Three hundred and thirty patients received adjuvant radiotherapy and 4802 patients did not receive radiotherapy. Median follow-up was 3.5 years. There was no difference in overall morbidity and mortality from any cardiac cause (p=0.13) in breast cancer patients who received adjuvant radiotherapy versus without radiotherapy by using modern radiotherapy techniques. CONCLUSION: There were no significant differences in cardiac morbidity and mortality after radiotherapy for breast cancer with a 9 year follow-up period in our population. PMID- 26359710 TI - Prognostic impact of preexisting hypertension and high systolic blood pressure at admission in patients hospitalized for systolic heart failure. AB - BACKGROUND: Higher systolic blood pressure (SBP) has been reported to be associated with a better prognosis in heart failure (HF) patients. This study aimed to investigate the prognostic impact of hypertension in patients hospitalized with systolic HF. METHODS: Pooled analysis of data from three Korean observational studies was performed. Patients >=18 years hospitalized with systolic HF (ejection fraction <=45%) (n=3538) were compared for the incidence of 1-year all-cause mortality according to the presence of preexisting hypertension and SBP quartiles on admission. RESULTS: Patients with hypertension (prevalence, 51.6%) presented more often with diabetes (43.9% vs. 23.0%, p<0.001) and chronic kidney disease (14.1% vs. 5.7%, p<0.001). During the 1-year follow-up, patients with hypertension showed similar cumulative incidences of all-cause mortality as those without hypertension (8.3% vs. 8.4%, p=0.900). Conversely, patients with higher SBP on admission had a lower incidence of all-cause death (quartile 4 vs. 1: 6.7% vs. 11.3%, p for trend=0.004). In the multivariate analysis, an increase in SBP of 10 mmHg was associated with an 8.5% risk reduction of all-cause death (hazard ratio: 0.915, 95% confidence interval: 0.853-0.981, p=0.013). CONCLUSIONS: Higher SBP on admission was independently associated with a lower risk of 1-year all-cause mortality in systolic HF. PMID- 26359712 TI - Cardioprotective mechanism of omega-3 polyunsaturated fatty acids. AB - Omega-3 polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid and docosahexaenoic acid, are widely regarded as cardioprotective. Several large scale, randomized clinical trials have shown that dietary intake of omega-3 PUFAs improves the prognosis of patients with symptomatic heart failure or recent myocardial infarction. Therefore, dietary consumption of omega-3 PUFA is recommended in international guidelines for the general population to prevent the occurrence of cardiovascular diseases (CVDs). However, the precise mechanisms underlying the cardioprotective effects of omega-3 PUFAs are not fully understood. Omega-3 PUFAs can be incorporated into the phospholipid bilayer of cell membranes and can affect membrane fluidity, lipid microdomain formation, and signaling across membranes. Omega-3 PUFAs also modulate the function of membrane ion channels, such as Na and L-type Ca channels, to prevent lethal arrhythmias. Moreover, omega-3 PUFAs also prevent the conversion of arachidonic acid into pro inflammatory eicosanoids by serving as an alternative substrate for cyclooxygenase or lipoxygenase, resulting in the production of less potent products. In addition, a number of enzymatically oxygenated metabolites derived from omega-3 PUFAs were recently identified as anti-inflammatory mediators. These omega-3 metabolites may contribute to the beneficial effects against CVDs that are attributed to omega-3 PUFAs. PMID- 26359711 TI - Randomized controlled trial of TY-51924, a novel hydrophilic NHE inhibitor, in acute myocardial infarction. AB - BACKGROUND: In patients with ST-elevation acute myocardial infarction (STEMI), reperfusion therapy limits infarct size, but can directly evoke myocardial reperfusion injury. Activation of the Na(+)/H(+) exchanger (NHE) plays an important role in reperfusion injury. TY-51924, a novel NHE inhibitor, significantly reduced infarct size in animal studies and was well tolerated in early-phase clinical trials. This study aim was to evaluate the efficacy and safety of TY-51924 in patients with STEMI. METHODS: In this multicenter, randomized, double-blind, placebo-controlled Phase II trial, 105 patients with first anterior STEMI undergoing primary percutaneous coronary intervention (pPCI) were randomly assigned to receive an intravenous infusion of either TY-51924 or placebo. Primary endpoints were myocardial salvage index (MSI) as determined by single photon emission computed tomography (SPECT) 3-5 days after pPCI and safety up to 7 days. RESULTS: Baseline characteristics were similar in the two groups. MSI 3-5 days after pPCI (0.200 vs. 0.290, p=0.56), 3 months after pPCI (0.470 vs. 0.500, p=0.76), and the incidences of side effects did not differ between the two groups as a whole. However, on post hoc analysis of 52 patients with a large area at risk (AAR) (>=38%) and no antegrade coronary flow, MSI by SPECT at 3 months after pPCI was significantly higher in TY-51924 group (0.450 vs. 0.320, p=0.03). TY-51924 did not adversely influence hemodynamics. CONCLUSIONS: TY-51924 did not improve MSI or increase side effects as a whole. However, TY-51924 is potentially cardioprotective in the presence of a large AAR and no antegrade coronary flow. PMID- 26359713 TI - Capturing the post-exertional exacerbation of fatigue following physical and cognitive challenge in patients with chronic fatigue syndrome. AB - OBJECTIVE: To design and validate an instrument to capture the characteristic post-exertional exacerbation of fatigue in patients with chronic fatigue syndrome (CFS). METHODS: Firstly, patients with CFS (N=19) participated in five focus group discussions to jointly explore the nature of fatigue and dynamic changes after activity, and inform development of a self-report instrument - the Fatigue and Energy Scale (FES). The psychometric properties of the FES were then examined in two case-control challenge studies: a physically-demanding challenge (moderate intensity aerobic exercise; N=10 patients), and a cognitively-demanding challenge (simulated driving; N=11 patients). Finally, ecological validity was evaluated by recording in association with tasks of daily living (N=9). RESULTS: Common descriptors for fatigue included 'exhaustion', 'tiredness', 'drained of energy', 'heaviness in the limbs', and 'foggy in the head'. Based on the qualitative data, fatigue was conceptualised as consisting of 'physical' and 'cognitive' dimensions. Analysis of the psychometric properties of the FES showed good sensitivity to the changing symptoms during a post-exertional exacerbation of fatigue following both physical exercise and driving simulation challenges, as well as tasks of daily living. CONCLUSION: The 'fatigue' experienced by patients with CFS covers both physical and cognitive components. The FES captured the phenomenon of a post-exertional exacerbation of fatigue commonly reported by patients with CFS. The characteristics of the symptom response to physical and cognitive challenges were similar. Both the FES and the challenge paradigms offer key tools to reliably investigate biological correlates of the dynamic changes in fatigue. PMID- 26359714 TI - The effects of intervention on the comprehension of irony and on hemispheric processing of irony in adults with ASD. AB - Individuals with autism spectrum disorders (ASD) experience difficulty in comprehending figurative language in general and irony in particular. The current study measured the effectiveness of a short-term intervention in enhancing the comprehension of irony. Twenty-nine adults with ASD and 22 typically developing (TD) adults participated in the study. Participants with ASD were randomly assigned to a study (intervention) or control (passive intervention) group. TD participants were also assigned to a passive intervention control group. The intervention improved comprehension of irony in the ASD group. Furthermore, responses to ironic and literal targets were similar within each hemisphere prior to the intervention within the ASD study group, but after the intervention responses lateralized to the right. Thus, following the intervention, participants with ASD demonstrated a pattern of hemispheric processing of ironic target words that resembled the pattern seen in the TD group prior to the intervention. Our findings suggest that an intervention that focuses on comprehension of irony improves performance of adults with ASD and affects the pattern of hemispheric processing of irony. PMID- 26359715 TI - The feeling of familiarity for music in patients with a unilateral temporal lobe lesion: A gating study. AB - Previous research has indicated that the medial temporal lobe (MTL), and more specifically the perirhinal cortex, plays a role in the feeling of familiarity for non-musical stimuli. Here, we examined contribution of the MTL to the feeling of familiarity for music by testing patients with unilateral MTL lesions. We used a gating paradigm: segments of familiar and unfamiliar musical excerpts were played with increasing durations (250, 500, 1000, 2000, 4000 ms and complete excerpts), and participants provided familiarity judgments for each segment. Based on the hypothesis that patients might need longer segments than healthy controls (HC) to identify excerpts as familiar, we examined the onset of the emergence of familiarity in HC, patients with a right MTL resection (RTR), and patients with a left MTL resection (LTR). In contrast to our hypothesis, we found that the feeling of familiarity was relatively spared in patients with a right or left MTL lesion, even for short excerpts. All participants were able to differentiate familiar from unfamiliar excerpts as early as 500 ms, although the difference between familiar and unfamiliar judgements was greater in HC than in patients. These findings suggest that a unilateral MTL lesion does not impair the emergence of the feeling of familiarity. We also assessed whether the dynamics of the musical excerpt (linked to the type and amount of information contained in the excerpts) modulated the onset of the feeling of familiarity in the three groups. The difference between familiar and unfamiliar judgements was greater for high than for low-dynamic excerpts for HC and RTR patients, but not for LTR patients. This indicates that the LTR group did not benefit in the same way from dynamics. Overall, our results imply that the recognition of previously well learned musical excerpts does not depend on the integrity of either right or the left MTL structures. Patients with a unilateral MTL resection may compensate for the effects of unilateral damage by using the intact contralateral temporal lobe. Moreover, we suggest that remote semantic memory for music might depend more strongly on neocortical structures rather than the MTL. PMID- 26359716 TI - Behavioural and electrophysiological effects related to semantic violations during braille reading. AB - This study investigated the potential to detect event related potentials (ERPs) occurring in response to a specific task in braille reading. This would expand current methodologies for studying the cognitive processes underlying braille reading. An N400 effect paradigm was utilised, whereby proficient blind braille readers read congruent- and incongruent-ending braille sentences. Kinematic and electroencephalography (EEG) data were obtained simultaneously and synchronised. The ERPs differed between the incongruent and congruent sentences in a manner consistent with the N400 effect found with a previous sighted reading paradigm, demonstrating that ERPs can be obtained during braille reading. The frequency of finger reversals and the degree of intermittency in the finger velocity were significantly higher when reading incongruent versus congruent sentence endings. Both reversals and the potential N400 effect may reflect processes involved in semantic unification. These findings have significant implications for the modelling of braille reading. The refinement of the technique will enable other ERPs to be identified and related to behavioural responses, to further our understanding of the braille reading process. PMID- 26359717 TI - Implications of recent findings for current cognitive models of familiar people recognition. AB - The aim of the present survey was to review clinical and experimental data concerning the visual (face), auditory (voice) and verbal (name) channels through which familiar people are recognized, by contrasting these data with assumptions made by modular cognitive models of familiar people recognition. Particular attention was paid to the fact that visual (face), auditory (voice) and verbal (name) recognition modalities have different hemispheric representations and that these asymmetries have important implications for cognitive models which have not considered hemispheric differences as an important variable in familiar people recognition. Several lines of research have, indeed, shown that familiar faces and voices are mainly underpinned by the right hemisphere, whereas names are mostly subsumed by the left hemisphere. Furthermore, anatomo-clinical data have shown that familiarity judgements are not generated at the level of the Person Identity Nodes (PINs), as suggested by influential cognitive models, but at the level of the modality-specific recognition units, with a right hemisphere dominance in the generation of face and voice familiarity feelings. Additionally, clinical and experimental data have shown that PINs should not be considered as a simple gateway to a unitary semantic system, which stores information about people in an abstract and amodal format, but as structures involved in the storage and retrieval of person-specific information, preferentially represented in a sensory-motor format in the right hemisphere and in a language-mediated format in the left hemisphere. Finally, clinical and experimental data have shown that before the level of the person identity nodes (PINs) a cross-communication exists between the perceptual channels concerning faces and voices, but not between the latter and personal names. These data show that person-specific representations are mainly based on perceptual (face and voice) information in the right hemisphere and on verbal information in the left hemisphere. PMID- 26359719 TI - The use of prognostic factors in metastatic renal cell carcinoma. AB - BACKGROUND: Over the last decade, the treatment landscape of metastatic renal cell carcinoma (mRCC) has evolved tremendously. The outcome of patients with mRCC has been improved since the advent of targeted therapy. OBJECTIVE: In this review, we address the use of prognostic schema in the era of targeted treatment. This article summarizes the current available prognostic models and the evidence to support their use in clinical settings. CONCLUSION: Prognostic models can help guide clinicians in their decision making, as they have been validated in the first- and second-line targeted therapy settings as well as in non-clear cell mRCC. Prognostic factors are important in patient counseling, clinical trial stratification, and therapy planning. Very selected favorable-risk patients with minimal bulk and slow-growing disease could potentially be observed before needing treatment. Patients with poor-risk disease may be eligible for treatment with temsirolimus. Patients with a very poor prognosis may not be suitable candidates for cytoreductive nephrectomy. New biomarkers are on the horizon, though their roles need to be validated and their additive contribution to improve existing prognostic models examined. PMID- 26359718 TI - Olfactory-visual integration facilitates perception of subthreshold negative emotion. AB - A fast growing literature of multisensory emotion integration notwithstanding, the chemical senses, intimately associated with emotion, have been largely overlooked. Moreover, an ecologically highly relevant principle of "inverse effectiveness", rendering maximal integration efficacy with impoverished sensory input, remains to be assessed in emotion integration. Presenting minute, subthreshold negative (vs. neutral) cues in faces and odors, we demonstrated olfactory-visual emotion integration in improved emotion detection (especially among individuals with weaker perception of unimodal negative cues) and response enhancement in the amygdala. Moreover, while perceptual gain for visual negative emotion involved the posterior superior temporal sulcus/pSTS, perceptual gain for olfactory negative emotion engaged both the associative olfactory (orbitofrontal) cortex and amygdala. Dynamic causal modeling (DCM) analysis of fMRI timeseries further revealed connectivity strengthening among these areas during crossmodal emotion integration. That multisensory (but not low-level unisensory) areas exhibited both enhanced response and region-to-region coupling favors a top-down (vs. bottom-up) account for olfactory-visual emotion integration. Current findings thus confirm the involvement of multisensory convergence areas, while highlighting unique characteristics of olfaction-related integration. Furthermore, successful crossmodal binding of subthreshold aversive cues not only supports the principle of "inverse effectiveness" in emotion integration but also accentuates the automatic, unconscious quality of crossmodal emotion synthesis. PMID- 26359720 TI - Different Apparent Gas Exchange Coefficients for CO2 and CH4: Comparing a Brown Water and a Clear-Water Lake in the Boreal Zone during the Whole Growing Season. AB - The air-water exchange of carbon dioxide (CO2) and methane (CH4) is a central process during attempts to establish carbon budgets for lakes and landscapes containing lakes. Lake-atmosphere diffusive gas exchange is dependent on the concentration gradient between air and surface water and also on the gas transfer velocity, often described with the gas transfer coefficient k. We used the floating-chamber method in connection with surface water gas concentration measurements to estimate the gas transfer velocity of CO2 (kCO2) and CH4 (kCH4) weekly throughout the entire growing season in two contrasting boreal lakes, a humic oligotrophic lake and a clear-water productive lake, in order to investigate the earlier observed differences between kCO2 and kCH4. We found that the seasonally averaged gas transfer velocity of CH4 was the same for both lakes. When the lakes were sources of CO2, the gas transfer velocity of CO2 was also similar between the two study lakes. The gas transfer velocity of CH4 was constantly higher than that of CO2 in both lakes, a result also found in other studies but for reasons not yet fully understood. We found no differences between the lakes, demonstrating that the difference between kCO2 and kCH4 is not dependent on season or the characteristics of the lake. PMID- 26359721 TI - Tomography, Radiography, and Rhinoscopy in Diagnosis of Benign and Malignant Lesions Affecting the Nasal Cavity and Paranasal Sinuses in Dogs: Comparative Study. AB - Canine nasal and paranasal diseases have variable causes. Presumptive diagnosis is based on clinical manifestations; however, high similarity of clinical signs often calls for diagnostic imaging modalities and rhinoscopy before a definitive diagnosis can be reached. This study sets out to determine the value of rhinoscopy, radiography, and computed tomography (CT) of the head for canine nasal and paranasal disease diagnosis using a purposely developed comparative score. In all, 20 dogs presenting with clinical signs consistent with nasal disease were used. Patients were submitted to radiographic, CT, and rhinoscopic assessment; rhinoscopy-guided biopsy collection was performed in cases presenting with tissue proliferation, ulceration, or other nasal mucosal lesions. Rhinoscopy and rhinoscopy combined with CT significantly contributed to nasal disease diagnosis. Rhinoscopy and CT are complementary diagnostic modalities. Rhinoscopy proved helpful for confirmation of presumptive diagnosis and allowed image assisted biopsy collection whereas CT contributed to effective determination of lesion extension and involvement of adjacent structures. Yet, histologic confirmation remains vital for definitive diagnosis. PMID- 26359722 TI - Why Psychology Matters in Veterinary Medicine. AB - As companion animals become more central to individuals and families, there are countless ways that veterinary medical practice can benefit from understanding human psychology. This article highlights how insights from the fields of health psychology and behavioral medicine might hold the potential to improve veterinary practice. We focus on key areas of care for companion animals that are integrally linked to their human caregivers' psychological reactions and behavior, including health maintenance, managing illness, and end-of-life care. We also note ways in which the challenges of skillfully negotiating interactions with companion animal caregivers and other stressful aspects of the veterinary profession may be informed by psychological and behavioral science expertise. PMID- 26359723 TI - Serum Ionized Calcium Quantification for Staging Canine Periodontal Disease: A Preliminary Study. AB - Periodontal diseases (PD) are infectious, inflammatory, progressive diseases of the oral cavity affecting people and dogs. PD takes 2 forms: gingivitis and periodontitis. Diagnosing or staging PD can be achieved only with dental x-rays and periodontal probing, both of which require the use of general anesthesia in dogs. This study aimed to determine whether serum ionized calcium ([iCa(2+)]) levels can be useful in preliminary PD staging in dogs. A sample of 40 dogs (n = 40) was divided into 4 groups (n = 10 each) based on the following PD stages: G1 (gingivitis), G2 (initial periodontitis), G3 (moderate periodontitis), and G4 (severe periodontitis). The groups were then subjected to [iCa(2+)] quantification. Statistically significant differences were observed between PD stages and [iCa(2+)] for all stages except G3 and G4. Therefore, this parameter can be used as an additional tool to establish and monitor preliminary PD status. PMID- 26359724 TI - Relationship Between Gender, Age, and Weight and the Serum Ionized Calcium Variations in Dog Periodontal Disease Evolution. AB - To analyze the relationships between gender, age, weight, and variations in the levels of serum ionized calcium ([iCa(2+)]) during periodontal disease (PD) evolution. In this study, dogs (n = 50) were divided into 5 groups according to the stage of PD: G0 (no PD), G1 (gingivitis), G2 (initial periodontitis), G3 (moderate periodontitis), and G4 (severe periodontitis). Statistically significant correlations were observed between age, [iCa(2+)] levels, and PD stage. Older dogs had lower [iCa(2+)] levels and more advanced PD stages (high positive correlation), and their body weight decreased as PD developed (negative correlation). Lower [iCa(2+)] values were associated with more severe PD. PMID- 26359725 TI - Canine Pancreas-Specific Lipase and C-reactive Protein in Dogs Treated With Anticonvulsants (Phenobarbital and Potassium Bromide). AB - Animals treated with anticonvulsant drugs may have increased canine pancreas specific lipase (cPLI) values. Inflammatory conditions and specifically acute pancreatitis are of major concern in these animals. Elevation in C-reactive protein is being associated with inflammatory status in dogs and it has been correlated with the clinical severity of pancreatitis. In the present study, we investigated if there is a correlation between the cPLI increase, changes in C reactive protein and hepatic enzymes, as well as the incidence of severe acute pancreatitis (AP) in dogs with anticonvulsant treatment (phenobarbital, or potassium bromide or both). Increased values of pancreas-specific lipase were found in 6.8% of the animals in treatment with anticonvulsants, and this increase is correlated with the increase in triglycerides, alkaline phosphatase, and alanine aminotransferase but not with C-reactive protein levels, which suggests a possible induction or release phenomenon rather than a clear severe AP. C reactive protein levels did not affect cPLI values on the population studied. Only 2 animals had clinical and analytical data suggestive of AP, indicating a low prevalence (0.6%). In conclusion, cPLI may be increased in a low percentage of animals with anticonvulsants treatment and its increase may not be associated with severe AP. It may be induced by the anticonvulsants drugs; however, further studies are advised to rule out other possible causes that increased cPLI. PMID- 26359726 TI - Pneumopericardium Secondary to Pneumomediastinum in a Golden Retriever Dog. AB - Pneumopericardium is a rare finding that has been previously reported following spontaneous, traumatic, or iatrogenic causes. A 3-year old Golden Retriever dog was admitted with respiratory distress after falling from a height. Clinical and electrocardiographic findings were nonspecific. Thoracic radiography revealed hyperinflated lung with sharp outlining of the mediastinal structures. A well demarcated region of radiolucent gas opacity was seen surrounding the cardiac silhouette. Echocardiography revealed intense hyper-reflective shadows all over the heart. Echocardiographic measurements were within the reference range. The dog responded well to conservative medical therapy. Pneumopericardium was reported secondary to pneumomediastinum; pneumopericardium is self-limiting unless other complications develop. PMID- 26359727 TI - Diagnosis and Treatment of Primary Erythrocytosis in a Dog: A Case Report. AB - Primary erythrocytosis, or polycythemia vera, is a myeloproliferative disease caused by the exaggerated increase of erythroid precursor cells in the bone marrow. We report the case of an 11-year-old male mixed-breed dog that had tachypnea and spastic tetraplegia. There was a significant increase in hematocrit. After phlebotomy and fluid therapy, the dog's condition improved. A diagnosis of primary erythrocytosis was supported by serum levels of erythropoietin. The dog responded well to treatment with administration of hydroxyurea (15 mg/kg), phlebotomies, and fluid therapy. However, after 18 months, he had an acute recurrence of clinical signs and was euthanized. We observed that long-term maintenance with hydroxyurea at a dosage of 15 mg/kg every 48 hours was adequate for managing polycythemia vera, with a survival time of 18 months in the present case. However, longer dose intervals are likely not appropriate. We believe that this may be helpful to other veterinarians facing the same problems in the treatment of polycythemia vera. PMID- 26359728 TI - Complete Situs Inversus in 2 Asymptomatic Dogs. AB - Complete situs inversus is a rare congenital condition that is characterized by the development of the thoracic and abdominal viscera in a mirror image to their normal orientation. This study describes this condition in 2 dogs: an 8-year-old male dalmatian that was originally evaluated for cystitis and a 3-year-old male crossbreed Pekinese that had a routine echographic study. In dogs, most of the reported cases were associated with the Kartagener syndrome, but our patients had no evidences of this ciliary disorder. PMID- 26359729 TI - Fatigue and soft tissue vibration during prolonged running. AB - Muscle tuning paradigm proposes that the mechanical properties of soft tissues are tuned in such a way that its vibration amplitude become minimized. Therefore, the vibrations of soft tissue are heavily damped. However, it has been hypothesized that the ability of muscle tuning decreases with fatigue. This study investigated the changes in vibration characteristics of soft tissue with fatigue. Vibrations of the gastrocnemius muscle of 8 runners during a prolonged run protocol on a treadmill at constant velocity (4 ms(-1)) were measured using a tri-axial accelerometer. The vibration amplitude is calculated using the Fourier transform and a wavelet-based method was used to calculate the damping coefficient. The results showed that: (1) the vibration amplitude in longitudinal direction increased with fatigue, which may be interpreted as the decreased muscle function with fatigue. (2) The amplitude increase percent strongly depended on the vibration frequency. (3) The damping coefficient of the gastrocnemius increased with fatigue. A 1-DOF mass-spring-damper model was used in order to validate the wavelet based method and simulate the observed phenomena. PMID- 26359730 TI - Delayed infection with Parvimonas micra following spinal instrumentation. AB - BACKGROUND CONTEXT: Delayed-onset surgical site infections following spinal instrumentation are uncommon and often present with chronic pain and implant failure. Anaerobic organisms are rarely implicated and identified with difficulty in these infections. PURPOSE: We report a case of vertebral osteomyelitis and epidural abscess due to Parvimonas micra, an anaerobic bacterium, six months following spinal instrumentation. STUDY DESIGN/SETTING: Case Report. RESULTS: P. micra was identified from multiple intraoperative tissue and hardware specimens. With hardware explant and antibiotic therapy, the patient had a successful outcome. CONCLUSIONS: To our knowledge, this is the first report of a P. micra hardware-associated spinal infection. PMID- 26359732 TI - Response to Letter to the Editor: Modulation of AQP-3 in burn wound: Comment on "Epidermal aquaporin-3 is increased in the cutaneous burn wound". PMID- 26359731 TI - Effects of Common Pesticides on Prostaglandin D2 (PGD2) Inhibition in SC5 Mouse Sertoli Cells, Evidence of Binding at the COX-2 Active Site, and Implications for Endocrine Disruption. AB - BACKGROUND: There are concerns that diminished prostaglandin action in fetal life could increase the risk of congenital malformations. Many endocrine-disrupting chemicals have been found to suppress prostaglandin synthesis, but to our knowledge, pesticides have never been tested for these effects. OBJECTIVES: We assessed the ability of pesticides that are commonly used in the European Union to suppress prostaglandin D2 (PGD2) synthesis. METHODS: Changes in PGD2 secretion in juvenile mouse Sertoli cells (SC5 cells) were measured using an ELISA. Coincubation with arachidonic acid (AA) was conducted to determine the site of action in the PGD2 synthetic pathway. Molecular modeling studies were performed to assess whether pesticides identified as PGD2-active could serve as ligands of the cyclooxygenase-2 (COX-2) binding pocket. RESULTS: The pesticides boscalid, chlorpropham, cypermethrin, cyprodinil, fenhexamid, fludioxonil, imazalil (enilconazole), imidacloprid, iprodione, linuron, methiocarb, o-phenylphenol, pirimiphos-methyl, pyrimethanil, and tebuconazole suppressed PGD2 production. Strikingly, some of these substances-o-phenylphenol, cypermethrin, cyprodinil, linuron, and imazalil (enilconazole)-showed potencies (IC50) in the range between 175 and 1,500 nM, similar to those of analgesics intended to block COX enzymes. Supplementation with AA failed to reverse this effect, suggesting that the sites of action of these pesticides are COX enzymes. The molecular modeling studies revealed that the COX-2 binding pocket can accommodate most of the pesticides shown to suppress PGD2 synthesis. Some of these pesticides are also capable of antagonizing the androgen receptor. CONCLUSIONS: Chemicals with structural features more varied than previously thought can suppress PGD2 synthesis. Our findings signal a need for in vivo studies to establish the extent of endocrine disrupting effects that might arise from simultaneous interference with PGD2 signaling and androgen action. CITATION: Kugathas S, Audouze K, Ermler S, Orton F, Rosivatz E, Scholze M, Kortenkamp A. 2016. Effects of common pesticides on prostaglandin D2 (PGD2) inhibition in SC5 mouse Sertoli cells, evidence of binding at the COX-2 active site, and implications for endocrine disruption. Environ Health Perspect 124:452-459; http://dx.doi.org/10.1289/ehp.1409544. PMID- 26359733 TI - Psychosocial adjustment following burns: An integrative literature review. AB - INTRODUCTION: Burn care innovations have vastly reduced mortality rates and improved prognoses, fostering the need for multi-disciplinary input in holistic recovery. Consequently psychological and social considerations post-burn are included in National Burn Care Standards and have featured increasingly in burns literature. AIM: To identify the key findings of the rapidly expanding literature base for psychosocial adjustment post-burn, highlighting the most important knowledge and future directions for both practice and research. METHOD: MEDLINE, CINAHL, EMBASE, PsycINFO, BNI, HMIC databases were searched from January 2003 to September 2013 using search terms regarding psychosocial adjustment post-burn. After exclusions 24 papers underwent critical appraisal. RESULTS: Studies were categorised by the element of adjustment that they examined; psychopathology, quality of life, return to work, interpersonal, post-traumatic growth. Strengths, weaknesses, and significant findings within each category were presented. DISCUSSION: Although psychopathology and quality of life were well-researched compared to other categories, all would benefit from methodological improvements such as sample size or dropout rates. Coping strategies, premorbid psychopathology, and personality consistently featured as predictors of adjustment, although research should now move from identifying predictors, to clarifying the concept and parameters of psychosocial adjustment while developing and evaluating interventions to improve outcomes. PMID- 26359734 TI - Do we need to talk? PMID- 26359735 TI - Infant autism: parents' role in ameliorating risk? PMID- 26359736 TI - What makes a difference in chronic fatigue syndrome? PMID- 26359737 TI - Considering new insights into antisociality and psychopathy. PMID- 26359738 TI - Protecting the mental health of women in the perinatal period. PMID- 26359739 TI - Rethinking the association between smoking and schizophrenia. PMID- 26359740 TI - Tears of Ishtar: women's mental health in Iraq. PMID- 26359743 TI - Trans* health: "diversity, not pathology". PMID- 26359741 TI - Former Armed Forces personnel in the Criminal Justice System. PMID- 26359744 TI - Shrunk. PMID- 26359745 TI - My immortal Holmes. PMID- 26359746 TI - The loss of mourning. PMID- 26359747 TI - No sex please: we're scientists. PMID- 26359748 TI - In the library, with the candlestick: English murder revisited. PMID- 26359750 TI - Rehabilitative therapies for chronic fatigue syndrome: a secondary mediation analysis of the PACE trial. AB - BACKGROUND: Cognitive behaviour therapy (CBT) added to specialist medical care (SMC), or graded exercise therapy (GET) added to SMC, are more effective in reducing fatigue and improving physical function than both adaptive pacing therapy (APT) plus SMC and SMC alone for chronic fatigue syndrome. We investigate putative treatment mechanisms. METHODS: We did a planned secondary mediation analysis of the PACE trial comparing SMC alone or SMC plus APT with SMC plus CBT and SMC plus GET for patients with chronic fatigue syndrome. 641 participants were recruited from six specialist chronic fatigue syndrome clinics in the UK National Health Service between March 18, 2005, and Nov 28, 2008. We assessed mediation using the product of coefficients method with the 12 week measure of the mediators and the 52 week measure of the outcomes. The primary outcomes were fatigue measured by the Chalder fatigue scale and physical function measured by the physical function subscale of the SF-36. We included confounder covariates and used treatment by mediator interaction terms to examine differences in mediator-outcome relations by treatment group. FINDINGS: The largest mediated effect for both CBT and GET and both primary outcomes was through fear avoidance beliefs with an effect of larger magnitude for GET (standardised effects *10, CBT vs APT, fatigue -1.22, 95% CI -0.52 to -1.97, physical function 1.54, 0.86 to 2.31; GET vs APT, fatigue -1.86, -0.80 to -2.89, physical function 2.35, 1.35 to 3.39). Increase in exercise tolerance (6 min walk distance) was a potent mediator of the effect of GET (vs APT, fatigue -1.37, 95% CI -0.76 to -2.21, physical function 1.90, 1.10 to 2.91), but not CBT. INTERPRETATION: Our main finding was that fear avoidance beliefs were the strongest mediator for both CBT and GET. Changes in both beliefs and behaviour mediated the effects of both CBT and GET, but more so for GET. The results support a treatment model in which both beliefs and behaviour play a part in perpetuating fatigue and disability in chronic fatigue syndrome. FUNDING: UK Medical Research Council, Department of Health for England, Scottish Chief Scientist Office, Department for Work and Pensions, National Institute for Health Research (NIHR), NIHR Biomedical Research Centre for Mental Health at South London and Maudsley NHS Foundation Trust, and Institute of Psychiatry, Psychology, and Neuroscience, King's College London. PMID- 26359749 TI - Parent-mediated intervention versus no intervention for infants at high risk of autism: a parallel, single-blind, randomised trial. AB - BACKGROUND: Risk markers for later autism identified in the first year of life present plausible intervention targets during early development. We aimed to assess the effect of a parent-mediated intervention for infants at high risk of autism on these markers. METHODS: We did a two-site, two-arm assessor-blinded randomised controlled trial of families with an infant at familial high risk of autism aged 7-10 months, testing the adapted Video Interaction to Promote Positive Parenting (iBASIS-VIPP) versus no intervention. Families were randomly assigned to intervention or no intervention groups using a permuted block approach stratified by centre. Assessors, but not families or therapists, were masked to group assignment. The primary outcome was infant attentiveness to parent. Regression analysis was done on an intention-to-treat basis. This trial is registered with ISCRTN Registry, number ISRCTN87373263. FINDINGS: We randomly assigned 54 families between April 11, 2011, and Dec 4, 2012 (28 to intervention, 26 to no intervention). Although CIs sometimes include the null, point estimates suggest that the intervention increased the primary outcome of infant attentiveness to parent (effect size 0.29, 95% CI -0.26 to 0.86, thus including possibilities ranging from a small negative treatment effect to a strongly positive treatment effect). For secondary outcomes, the intervention reduced autism-risk behaviours (0.50, CI -0.15 to 1.08), increased parental non directiveness (0.81, 0.28 to 1.52), improved attention disengagement (0.48, -0.01 to 1.02), and improved parent-rated infant adaptive function (chi(2)[2] 15.39, p=0.0005). There was a possibility of nil or negative effect in language and responsivity to vowel change (P1: ES-0.62, CI -2.42 to 0.31; P2: -0.29, -1.55 to 0.71). INTERPRETATION: With the exception of the response to vowel change, our study showed positive estimates across a wide range of behavioural and brain function risk-markers and developmental outcomes that are consistent with a moderate intervention effect to reduce the risk for later autism. However, the estimates have wide CIs that include possible nil or small negative effects. The results are encouraging for development and prevention science, but need larger scale replication to improve precision. FUNDING: Autistica, Waterloo Foundation, Autism Speaks, and the UK Medical Research Council. PMID- 26359751 TI - Punishment and psychopathy: a case-control functional MRI investigation of reinforcement learning in violent antisocial personality disordered men. AB - BACKGROUND: Men with antisocial personality disorder show lifelong abnormalities in adaptive decision making guided by the weighing up of reward and punishment information. Among men with antisocial personality disorder, modification of the behaviour of those with additional diagnoses of psychopathy seems particularly resistant to punishment. METHODS: We did a case-control functional MRI (fMRI) study in 50 men, of whom 12 were violent offenders with antisocial personality disorder and psychopathy, 20 were violent offenders with antisocial personality disorder but not psychopathy, and 18 were healthy non-offenders. We used fMRI to measure brain activation associated with the representation of punishment or reward information during an event-related probabilistic response-reversal task, assessed with standard general linear-model-based analysis. FINDINGS: Offenders with antisocial personality disorder and psychopathy displayed discrete regions of increased activation in the posterior cingulate cortex and anterior insula in response to punished errors during the task reversal phase, and decreased activation to all correct rewarded responses in the superior temporal cortex. This finding was in contrast to results for offenders without psychopathy and healthy non-offenders. INTERPRETATION: Punishment prediction error signalling in offenders with antisocial personality disorder and psychopathy was highly atypical. This finding challenges the widely held view that such men are simply characterised by diminished neural sensitivity to punishment. Instead, this finding indicates altered organisation of the information-processing system responsible for reinforcement learning and appropriate decision making. This difference between violent offenders with antisocial personality disorder with and without psychopathy has implications for the causes of these disorders and for treatment approaches. FUNDING: National Forensic Mental Health Research and Development Programme, UK Ministry of Justice, Psychiatry Research Trust, NIHR Biomedical Research Centre. PMID- 26359752 TI - Pathways to perinatal depressive symptoms after mass conflict in Timor-Leste: a modelling analysis using cross-sectional data. AB - BACKGROUND: The contributions of potentially traumatic events (PTEs) of mass conflict and post-traumatic stress disorder (PTSD) symptoms to perinatal depression in women living in low-income, post-conflict countries are unclear. We tested a model including these factors, intimate partner violence (IPV), and continuing adversity in women in Timor-Leste. METHODS: Our modelling study used cross-sectional data from a sample of women living in two districts in Timor Leste, identified through service registers, clinic records, village chiefs, and a door-to-door survey between June, 2012, and June, 2013. Eligible women were 3-6 months pregnant or 3-6 months postpartum. We assessed conflict-related PTEs, IPV, continuing adversity (poverty and insecurity), PTSD symptoms (the Harvard Trauma Questionnaire), and maternal depressive symptoms (the Edinburgh Postnatal Depression Scale [EPDS]) to develop a theoretical model to examine pathways leading directly and indirectly to depressive symptoms. FINDINGS: We assessed 427 eligible women, of whom 258 (60%) were pregnant and 169 (40%) were postnatal. 87 (22%) of 387 women who were given the EPDS to complete were above the threshold used to define depression, and 40 (9%) of 427 were regarded as having PTSD. Our most comprehensive model showed that IPV and conflict-related deprivations led directly to depressive symptoms as well as to continuing adversity. Human rights related trauma, witnessing murder, and a further path from IPV led to PTSD symptoms. Human rights-related trauma also led to continuing adversity. Paths from continuing adversity led to depressive symptoms, and PTSD symptoms, which was the predominant path. We noted a strong and unidirectional path from PTSD symptoms to depressive symptoms. INTERPRETATION: Protection of women from human rights abuses, prevention of IPV, reduction in insecurity and poverty in the post conflict period, and identification of and treatment for PTSD symptoms might reduce the risk of perinatal depression in post-conflict, low-income countries. Longitudinal studies are needed to confirm these findings. FUNDING: Australian National Health and Medical Research Council. PMID- 26359753 TI - The role of global traditional and complementary systems of medicine in the treatment of mental health disorders. AB - Traditional and complementary systems of medicine include a broad range of practices, which are commonly embedded in cultural milieus and reflect community beliefs, experiences, religion, and spirituality. Two major components of this system are discernible: complementary alternative medicine and traditional medicine, with different clientele and correlates of patronage. Evidence from around the world suggests that a traditional or complementary system of medicine is commonly used by a large number of people with mental illness. Practitioners of traditional medicine in low-income and middle-income countries fill a major gap in mental health service delivery. Although some overlap exists in the diagnostic approaches of traditional and complementary systems of medicine and conventional biomedicine, some major differences exist, largely in the understanding of the nature and cause of mental disorders. Treatments used by providers of traditional and complementary systems of medicine, especially traditional and faith healers in low-income and middle-income countries, might sometimes fail to meet widespread understandings of human rights and humane care. Nevertheless, collaborative engagement between traditional and complementary systems of medicine and conventional biomedicine might be possible in the care of people with mental illness. The best model to bring about that collaboration will need to be established by the needs of the extant mental health system in a country. Research is needed to provide an empirical basis for the feasibility of such collaboration, to clearly delineate its boundaries, and to test its effectiveness in bringing about improved patient outcomes. PMID- 26359754 TI - Global mental health and neuroscience: potential synergies. AB - Global mental health has emerged as an important specialty. It has drawn attention to the burden of mental illness and to the relative gap in mental health research and services around the world. Global mental health has raised the question of whether this gap is a developmental issue, a health issue, a human rights issue, or a combination of these issues-and it has raised awareness of the need to develop new approaches for building capacity, mobilising resources, and closing the research and treatment gap. Translational neuroscience has also advanced. It comprises an important conceptual approach to understanding the neurocircuitry and molecular basis of mental disorders, to rethinking how best to undertake research on the aetiology, assessment, and treatment of these disorders, with the ultimate aim to develop entirely new approaches to prevention and intervention. Some apparent contrasts exist between these fields; global mental health emphasises knowledge translation, moving away from the bedside to a focus on health systems, whereas translational neuroscience emphasises molecular neuroscience, focusing on transitions between the bench and bedside. Meanwhile, important opportunities exist for synergy between the two paradigms, to ensure that present opportunities in mental health research and services are maximised. Here, we review the approaches of global mental health and clinical neuroscience to diagnosis, pathogenesis, and intervention, and make recommendations for facilitating an integration of these two perspectives. PMID- 26359755 TI - What to do when a psychotherapy fails. PMID- 26359756 TI - ODYSSEAS: supervised use of drugs versus bureaucracy in Greece. PMID- 26359757 TI - Is change possible? PMID- 26359758 TI - Elaborately designed diblock nanoprobes for simultaneous multicolor detection of microRNAs. AB - Simultaneous detection of multiple biomarkers has important prospects in the biomedical field. In this work, we demonstrated a novel strategy for the detection of multiple microRNAs (miRNAs) based on gold nanoparticles (Au NPs) and polyadenine (polyA) mediated nanoscale molecular beacon (MB) probes (denoted p nanoMBs). Novel fluorescent labeled p-nanoMBs bearing consecutive adenines were designed, of which polyA served as an effective anchoring block binding to the surface of Au NPs, and the appended hairpin block formed an upright conformation that favored the hybridization with targets. Using the co-assembling method and the improved hybridization conformation of the hairpin probes, we achieved high selectivity for specifically distinguishing DNA targets from single-base mismatched DNA targets. We also realized multicolor detection of three different synthetic miRNAs in a wide dynamic range from 0.01 nM to 200 nM with a detection limit of 10 pM. What's more, we even detected miRNAs in a simulated serum environment, which indicated that our method could be used in complex media. Compared with the traditional method, our strategy provides a promising alternative method for the qualitative and quantitative detection of miRNAs. PMID- 26359759 TI - Actin cytoskeleton differentially alters the dynamics of lamin A, HP1alpha and H2B core histone proteins to remodel chromatin condensation state in living cells. AB - Cells in physical microenvironments regulate their functioning and geometry in response to mechanical stimuli. Recent studies have demonstrated the influence of the integrated actin cytoskeleton on nuclear integrity and chromatin organization. However, the mechanisms underlying the mechanotransduction of their physical coupling to nuclear protein dynamics are not well understood. In this study, we take advantage of micropatterned geometric substrates in NIH3T3 mouse fibroblasts to probe the functional influence of actin organization on nuclear lamina and chromatin assembly. Fluorescence correlation spectroscopy studies demonstrate that stabilization of perinuclear actin strengthens the transient interactions of lamin A with the chromatin. Correspondingly, fluorescence recovery after photobleaching studies reveal enhanced mobility of these nuclear lamina proteins when actin organization is perturbed. Combining these fluorescence dynamics assays, we also demonstrate an actin-driven differential modulation of core histone H2B and heterochromatin HP1alpha protein dynamics with chromatin. These altered dynamics are reflected structurally by concomitant changes in the architecture of the heterochromatin foci as seen by immunofluorescence assays. Taken together, our study provides a demonstration of the differential mechanical control of perinuclear actin on the dynamics of the nuclear lamina, euchromatin and heterochromatin regimes of the nucleus, and suggests an actin-mediated route to spatially and structurally tune chromatin organization and dynamics. PMID- 26359760 TI - Nanolayered tin phosphate: a remarkably selective Cs ion sieve for acidic waste solutions. AB - Herein, we report a unique tin phosphate that is remarkably selective to (137)Cs(+) from extremly acidic solutions because of its special layered structure with an unusually large interlayer space. This acidic exchanger is superior to other existing materials in terms of its selectivity and capacity for (137)Cs(+) from acidic solutions. PMID- 26359762 TI - Chemical Visualization of a GaN p-n junction by XPS. AB - We report on an operando XPS investigation of a GaN diode, by recording the Ga2p3/2 peak position under both forward and reverse bias. Areal maps of the peak positions under reverse bias are completely decoupled with respect to doped regions and allow a novel chemical visualization of the p-n junction in a 2-D fashion. Other electrical properties of the device, such as leakage current, resistivity of the domains are also tapped via recording line-scan spectra. Application of a triangular voltage excitation enables probing photoresponse of the device. PMID- 26359761 TI - Selective Negative Allosteric Modulation Of Metabotropic Glutamate Receptors - A Structural Perspective of Ligands and Mutants. AB - The metabotropic glutamate receptors have a wide range of modulatory functions in the central nervous system. They are among the most highly pursued drug targets, with relevance for several neurological diseases, and a number of allosteric modulators have entered clinical trials. However, so far this has not led to a marketed drug, largely because of the difficulties in achieving subtype-selective compounds with desired properties. Very recently the first crystal structures were published for the transmembrane domain of two metabotropic glutamate receptors in complex with negative allosteric modulators. In this analysis, we make the first comprehensive structural comparison of all metabotropic glutamate receptors, placing selective negative allosteric modulators and critical mutants into the detailed context of the receptor binding sites. A better understanding of how the different mGlu allosteric modulator binding modes relates to selective pharmacological actions will be very valuable for rational design of safer drugs. PMID- 26359763 TI - Mobility-Enhancing Coatings for Vitreoretinal Surgical Devices: Hydrophilic and Enzymatic Coatings Investigated by Microrheology. AB - Ophthalmic wireless microrobots are proposed for minimally invasive vitreoretinal surgery. Devices in the vitreous experience nonlinear mobility as a result of the complex mechanical properties of the vitreous and its interaction with the devices. A microdevice that will minimize its interaction with the macromolecules of the vitreous (i.e., mainly hyaluronan (HA) and collagen) can be utilized for ophthalmic surgeries. Although a few studies on the interactions between the vitreous and microdevices exist, there is no literature on the influence of coatings on these interactions. This paper presents how coatings on devices affect mobility in the vitreous. Surgical catheters in the vasculature use hydrophilic polymer coatings that reduce biomolecular absorption and enhance mobility. In this work such polymers, polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), and HA coatings were utilized, and their effects on mobility in the vitreous were characterized. Hydrophilic titanium dioxide (TiO2) coating was also developed and characterized. Collagenase and hyaluronidase enzymes were coated on probes' surfaces with a view to enhancing their mobility by enzymatic digestion of the collagen and HA of the vitreous, respectively. To model the human vitreous, ex vivo porcine vitreous and collagen were used. For studying the effects of hyaluronidase, the vitreous and HA were used. The hydrophilic and enzymatic coatings were characterized by oscillatory magnetic microrheology. The statistical significance of the mean relative displacements (i.e., mobility) of the coated probes with respect to control probes was assessed. All studied hydrophilic coatings improve mobility, except for HA which decreases mobility potentially due to bonding with vitreal macromolecules. TiO2 coating improves mobility in collagen by 28.3% and in the vitreous by 15.4%. PEG and PVP coatings improve mobility in collagen by 19.4 and by 39.6%, respectively, but their improvement in the vitreous is insignificant at a 95% confidence level (CL). HA coating affects mobility by reducing it in collagen by 35.6% (statistically significant) and in the vitreous by 16.8% (insignificant change at 95% CL). The coatings cause similar effects in collagen and in the vitreous. However, the effects are lower in the vitreous, which can be due to a lower concentration of collagen in the vitreous than in the prepared collagen samples. The coatings based on enzymatic activity increase mobility (i.e., >40% after 15 min experiments in the vitreous models) more than the hydrophilic coatings based on physicochemical interactions. However, the enzymes have time-dependent effects, and they dissolve from the probe surface with time. The presented results are useful for researchers and companies developing ophthalmic devices. They also pave the way to understanding how to adjust mobility of a microdevice in a complex fluid by choice of an appropriate coating. PMID- 26359764 TI - Down-regulation of miR-326 is associated with poor prognosis and promotes growth and metastasis by targeting FSCN1 in gastric cancer. AB - BACKGROUND: MicroRNAs (miRNAs) have been documented as playing important roles in diverse biological processes including tumorigenesis. However, the function and mechanism of miR-326 in gastric cancer are still unknown. The aim of this study is to identify the role of miR-326 in gastric cancer and clarify the regulation of Fascin1 (FSCN1) by miR-326. METHODS: The expression levels of miR-326 were detected in gastric cancer samples and cell lines by real-time PCR. The clinical and prognostic significance of miR-326 in gastric cancer patients were analyzed. Furthermore, the function of miR-326 on tumor cell growth and mobility were explored through MTT, colony formation, Transwell migration and invasion assays in vitro. A miR-326 target was confirmed using luciferase reporter assays, real time PCR and Western blot. RESULTS: Our study showed that miR-326 expression was decreased in gastric cancer tissues and cell lines, and low expression of miR-326 was associated to clinical stage, tumor depth, lymph node metastasis and distant metastasis. In survival analysis, low expression of miR-326 was a poor independent prognostic factor for gastric cancer patients. Gain-of-function and loss-of-function studies showed that miR-326 served as a tumor suppressor regulating gastric cancer cells growth, migration and invasion. Furthermore, we identified FSCN1 as the functional target of miR-326 by directly targeting the 3' UTR of FSCN1. CONCLUSIONS: Our study demonstrated that miR-326 overexpression was a poor prognostic marker for gastric cancer patients, and miR-326 served as a tumor suppressor in gastric cancer via directly regulating FSCN1. PMID- 26359765 TI - A Comparative Meta-Analysis of Tick Paralysis in the United States and Australia. AB - CONTEXT: Tick paralysis is a neurotoxic envenoming that mimics polio and primarily afflicts children, especially in hyperendemic regions of the Western United States of America (US) and Eastern Australia. OBJECTIVE: To compare the epidemiology, clinical and electrodiagnostic manifestations, and outcomes of tick paralysis in the US versus Australia. METHODS: A comparative meta-analysis of the scientific literature was conducted using Internet search engines to identify confirmed cases of tick paralysis in the US and Australia. Continuous variables including age, time to tick removal, and duration of paralysis were analyzed for statistically significant differences by unpaired t-tests; and categorical variables including gender, regional distribution, tick vector, tick attachment site, and misdiagnosis were compared for statistically significant differences by chi-square or Fisher exact tests. RESULTS: Tick paralysis following ixodid tick bites occurred seasonally and sporadically in individuals and in more clusters of children than in adults of both sexes in urban and rural locations in North America and Australia. The case fatality rate for tick paralysis was low, and the proportion of misdiagnoses of tick paralysis as Guillain-Barre syndrome (GBS) was greater in the US than in Australia. Although electrodiagnostic manifestations were similar, the neurotoxidromes differed significantly with prolonged weakness and even residual neuromuscular paralysis following tick removal in Australian cases compared with US cases. DISCUSSION: Tick paralysis was a potentially lethal envenoming that occurred in children and adults in a seasonally and regionally predictable fashion. Tick paralysis was increasingly misdiagnosed as GBS during more recent reporting periods in the US. Such misdiagnoses often directed unnecessary therapies including central venous plasmapheresis with intravenous immunoglobulin G that delayed correct diagnosis and tick removal. CONCLUSION: Tick paralysis should be added to and quickly excluded from the differential diagnoses of acute ataxia with ascending flaccid paralysis, especially in children living in tick paralysis-endemic regions worldwide. PMID- 26359766 TI - Pediatric hydrocephalus: 40-year outcomes in 128 hydrocephalic patients treated with shunts during childhood. Assessment of surgical outcome, work participation, and health-related quality of life. AB - OBJECT: Treatment for hydrocephalus has not advanced appreciably since the advent of CSF shunts more than 50 years ago. The outcome for pediatric patients with hydrocephalus has been the object for several studies; however, much uncertainty remains regarding the very long term outcome for these patients. Shunting became the standard treatment for hydrocephalus in Norway during the 1960s, and the first cohorts from this era have now reached middle age. Therefore, the objective of this study was to review surgical outcome, mortality, social outcome, and health-related quality of life in middle-aged patients treated for hydrocephalus during childhood. METHODS: Data were collected in all patients, age 14 years or less, who required a CSF shunt during the years 1967-1970. Descriptive statistics were assessed regarding patient characteristics, surgical features, social functioning, and work participation. The time and cause of death, if applicable, were also determined. Kaplan-Meier survival estimates were used to determine the overall survival of patients. Information regarding self-perceived health and functional status was assessed using the 36-Item Short Form Health Survey (SF-36) and the Barthel Index score. RESULTS: A total of 128 patients were included in the study, with no patient lost to follow-up. Of the 128 patients in the study, 61 (47.6%) patients died during the 42-45 years of observation. The patients who died belonged to the tumor group (22 patients) and the myelomeningocele group (13 patients). The mortality rate was lowered to 39% if the patients with tumors were excluded. The overall mortality rates at 1, 2, 10, 20, and 40 years from time of initial shunt insertion were 16%, 24%, 31%, 40%, and 48% respectively. The incidence of shunt-related mortality was 8%. The majority of children graduated from a normal school (67%) or from a school specializing in education for physically handicapped children (20%). Self-perceived health was significantly poorer in 6 out of 8 domains assessed by SF-36 as compared with the background population. Functional status among the survivors varied greatly during the follow-up period, but the majority of patients were self-dependent. A total of 56% of the patients were socially independent, and 42% of the patients were employed. CONCLUSIONS: Approximately half of the patients are still alive. During the 42-45 year follow-up period, the mortality rate was 48%. Two deaths were due to acute shunt failure, and at least 8% of the deaths were shunt related (probable or late onset). The morbidity in middle-aged individuals treated for pediatric hydrocephalus is considerable. The late mortality rate was low, but not negligible. Twelve patients died during the last 2 decades, 1 of whom died because of acute shunt failure. Although the shunt revision rate was decreasing during the study period, many patients required shunt surgery during adulthood. Forty-one revisions in 21 patients were performed during the last decade. Thus, there is an obvious need for life-long follow-up in these patients. PMID- 26359767 TI - Pleiotropic Role of Dietary Phytochemicals in Cancer: Emerging Perspectives for Combinational Therapy. AB - Cancer is considered a complicated health issue worldwide. The mean cancer survival through standard therapeutic strategies has not been significantly improved over the past few decades. Hence, alternate remedies are needed to treat or prevent this dreadful disease being explored. Currently, it has been recognized that repeated treatment with chemotherapeutic agents has been largely ineffective due to multidrug resistance and further conventional treatment possesses limited drug accessibility to cancerous tissues, which in turn necessitates a higher dose resulting in increased cytotoxicity. Drug combinations have been practiced to address the problems associated with conventional single drug treatment. Recently, natural dietary agents have attracted much attention in cancer therapy because of their synergistic effects with anticancer drugs against different types of cancer. Natural phytochemicals may execute their anticancer activity through targeting diverse cancer cell signaling pathways, promoting cell cycle arrest and apoptosis, regulating antioxidant status and detoxification. This review focuses mainly on the anticancer efficacy of dietary phytochemicals in combination with standard therapeutic drugs reported from various in vitro and in vivo experimental studies apart from clinical trials. This review adds knowledge to the field of intervention studies using combinational modalities that opens a new window for cancer treatment/chemoprevention. PMID- 26359768 TI - 'I still have difficulties feeling like a mother': The transition to motherhood of preterm infants mothers. AB - OBJECTIVE: The premature birth of their infant can constitute a sudden interruption of the transition to motherhood that requires a reorganisation of the process. The present study aimed to analyse the experience of the transition to motherhood of preterm infants' mothers, framing it within Stern's transition to motherhood theory. METHOD: A semi-structured interview was administered to 30 mothers during the recovery of the infant in the Neonatal Intensive Care Unit. The interview explored the experience of mothers related to pregnancy, the infant's birth and recovery. RESULTS: Thematic Analyses evidenced four interrelated themes: disconnection from the child, perception of maternal inadequacy, loss of parental role and temporal suspension. The themes showed that the mothers' experience of preterm birth not only concerns the traumatic delivery, but is also embedded in the entire process of becoming a mother within an institutional context. CONCLUSIONS: Results were connected to Stern's theory. Findings revealed difficulties for preterm mothers that could affect the development of the maternal constellation and thus their transition to motherhood. These difficulties may influence the construction of maternal identity, mother's representation of their child and the bond with their child. PMID- 26359769 TI - Observation of an Orientation Change in Highly Oriented Layer-by-Layer Films of a Ruthenium Complex upon Oxidation Reaction. AB - Layer-by-layer films composed of redox-active ruthenium dimer and Zr(IV) ions were fabricated on an indium tin oxide electrode. The fabricating behavior was monitored by cyclic voltammetry and UV-vis absorption spectral measurements. The orientation of the film was also monitored by grazing-incidence small-angle and wide-angle X-ray scattering (GISAXS) measurements, and it has been clarified that this film has a crystalline structure. The peaks obtained by GISAXS were changed upon oxidation reaction, which indicates that a change in the orientation of the ruthenium dimer occurred in the film. PMID- 26359770 TI - Engineering Veterinary Education. PMID- 26359772 TI - Tending Animals in the Global Village: A Guide to International Veterinary Medicine. AB - David M. Sherman, Tending Animals In The Global Village: A Guide To International Veterinary Medicine, 495 pages Lippincott, Williams & Wilkins ISBN 0-683-18051-7, reviewed by Corrie Brown, DVM, PhD. PMID- 26359771 TI - A Crisis of Lost Opportunity-Conclusions from a Symposium on Challenges for Animal Population Health Education. PMID- 26359774 TI - Generating neuronal diversity in the mammalian cerebral cortex. AB - The neocortex is the part of the brain responsible for execution of higher-order brain functions, including cognition, sensory perception, and sophisticated motor control. During evolution, the neocortex has developed an unparalleled neuronal diversity, which still remains partly unclassified and unmapped at the functional level. Here, we broadly review the structural blueprint of the neocortex and discuss the current classification of its neuronal diversity. We then cover the principles and mechanisms that build neuronal diversity during cortical development and consider the impact of neuronal class-specific identity in shaping cortical connectivity and function. PMID- 26359775 TI - Polarized protein transport and lumen formation during epithelial tissue morphogenesis. AB - One of the major challenges in biology is to explain how complex tissues and organs arise from the collective action of individual polarized cells. The best studied model of this process is the cross talk between individual epithelial cells during their polarization to form the multicellular epithelial lumen during tissue morphogenesis. Multiple mechanisms of apical lumen formation have been proposed. Some epithelial lumens form from preexisting polarized epithelial structures. However, de novo lumen formation from nonpolarized cells has recently emerged as an important driver of epithelial tissue morphogenesis, especially during the formation of small epithelial tubule networks. In this review, we discuss the latest findings regarding the mechanisms and regulation of de novo lumen formation in vitro and in vivo. PMID- 26359776 TI - Metabolism and epigenetics. AB - Epigenetic mechanisms by which cells inherit information are, to a large extent, enabled by DNA methylation and posttranslational modifications of histone proteins. These modifications operate both to influence the structure of chromatin per se and to serve as recognition elements for proteins with motifs dedicated to binding particular modifications. Each of these modifications results from an enzyme that consumes one of several important metabolites during catalysis. Likewise, the removal of these marks often results in the consumption of a different metabolite. Therefore, these so-called epigenetic marks have the capacity to integrate the expression state of chromatin with the metabolic state of the cell. This review focuses on the central roles played by acetyl-CoA, S adenosyl methionine, NAD(+), and a growing list of other acyl-CoA derivatives in epigenetic processes. We also review how metabolites that accumulate as a result of oncogenic mutations are thought to subvert the epigenetic program. PMID- 26359777 TI - Lung endoderm morphogenesis: gasping for form and function. AB - The respiratory endoderm develops from a small cluster of cells located on the ventral anterior foregut. This population of progenitors generates the myriad epithelial lineages required for proper lung function in adults through a complex and delicately balanced series of developmental events controlled by many critical signaling and transcription factor pathways. In the past decade, understanding of this process has grown enormously, helped in part by cell lineage fate analysis and deep sequencing of the transcriptomes of various progenitors and differentiated cell types. This review explores how these new techniques, coupled with more traditional approaches, have provided a detailed picture of development of the epithelial lineages in the lung and insight into how aberrant development can lead to lung disease. PMID- 26359778 TI - Monoallelic expression of olfactory receptors. AB - The sense of smell collects vital information about the environment by detecting a multitude of chemical odorants. Breadth and sensitivity are provided by a huge number of chemosensory receptor proteins, including more than 1,400 olfactory receptors (ORs). Organizing the sensory information generated by these receptors so that it can be processed and evaluated by the central nervous system is a major challenge. This challenge is overcome by monogenic and monoallelic expression of OR genes. The single OR expressed by each olfactory sensory neuron determines the neuron's odor sensitivity and the axonal connections it will make to downstream neurons in the olfactory bulb. The expression of a single OR per neuron is accomplished by coupling a slow chromatin-mediated activation process to a fast negative-feedback signal that prevents activation of additional ORs. Singular OR activation is likely orchestrated by a network of interchromosomal enhancer interactions and large-scale changes in nuclear architecture. PMID- 26359779 TI - The complete chloroplast genome of Cupressus gigantea, an endemic conifer species to Qinghai-Tibetan Plateau. AB - The complete chloroplast genome of the wild Cupressus gigantea (Cupressaceae) is determined in this study. The circular genome is 128 244 bp in length with 115 single copy genes and two duplicated genes (trnI-CAU and trnQ-UUG). This genome contains 82 protein-coding genes, four ribosomal RNA genes and 31 transfer RNA genes. In these genes, eight genes (atpF, rpoC1, ndhA, ndhB, petB, petD, rpl16 and rpl2) harbor a single intron and two genes (rps12 and ycf3) harbor two introns. This genome does not contain canonical IRs, and the overall GC content is 34.7%. A maximum parsimony phylogenetic analysis revealed that C. gigantea and C. sempervirens are more closely related. PMID- 26359780 TI - Novel Kinetic Strategies Adopted in Asymmetric Split-Belt Treadmill Walking. AB - The hip and ankle strategies that affect learning of a novel gait have not been fully determined, and could be of importance in design of clinical gait interventions. The authors' purpose was to determine the effects of asymmetric split-belt treadmill walking on ankle and hip work during propulsion. Participants were randomized into either a gradual training group or a sudden training group and later returned for a retention test. The gradual training group performed significantly more work at the hip joint of the slow limb during acquisition, and decreased the hip joint work performed during retention. These findings reveal the hip joint on the slow limb during initial swing as a possible site of adaptation to a novel locomotor pattern. PMID- 26359781 TI - Proton Transverse Relaxation as a Sensitive Probe for Structure Determination in Solid Proteins. AB - Solid-state nuclear magnetic resonance (NMR) spectroscopy has been successfully applied to elucidate the atomic-resolution structures of insoluble proteins. The major bottleneck is the difficulty to obtain valuable long-distance structural information. Here, we propose the use of distance restraints as long as 32 A, obtained from the quantification of transverse proton relaxation induced by a methanethiosulfonate spin label (MTSL). Combined with dipolar proton-proton distance restraints, this method allows us to obtain protein structures with excellent precision from single spin-labeled 1 mg protein samples using fast magic angle spinning. PMID- 26359782 TI - Structural studies of parkin and sacsin: Mitochondrial dynamics in neurodegenerative diseases. AB - Neurodegenerative diseases are prevalent, chronic diseases emanating from the dysfunction or death of neurons. The disrupted mitochondrial dynamics observed in a large number of neurodegenerative diseases suggests a common etiology with the possibility of therapies targeting multiple diseases. This review highlights the contributions of structural studies of disease-related proteins to the understanding of neurodegenerative disease pathogenesis and especially the cellular events leading to disruptions in mitochondrial dynamics and function. The examples used are parkin and sacsin, two proteins linked respectively to autosomal-recessive early-onset PD and autosomal-recessive spastic ataxia of Charlevoix-Saguenay. Structural studies of parkin and sacsin explain the pathogenicity of a large number of disease-associated mutations and reveal insights into their cellular functions related to mitochondrial dynamics. PMID- 26359783 TI - Development of Nutraceutical Emulsions as Risperidone Delivery Systems: Characterization and Toxicological Studies. AB - Emulsions are gaining increasing interest to be applied as drug delivery systems. The main goal of this work was the formulation of an oil/water nutraceutical emulsion (NE) for oral administration, enriched in omega 3 (omega3) and omega 6 (omega6), and able to encapsulate risperidone (RISP), an antipsychotic drug widely used in the treatment of autism spectrum disorders (ASD). RISP has low solubility in aqueous medium and poor bioavailability because of its metabolism and high protein binding. Coadministration of omega3, omega3, and vitamin E complexed with RISP might increase its bioavailability and induce a synergistic effect on the treatment of ASD. Here, we developed an easy and quick method to obtain NEs and then optimized them. The best formulation was chosen after characterization by particle size, defects of the oil-in-water interface, zeta potential (ZP), and in vitro drug release. The formulation selected was stable over time, with a particle size of around 3 MUm, a ZP lower than -20 mV and controlled drug release. To better understand the biochemical properties of the formulation obtained, we studied in vitro toxicity in the Caco-2 cell line. After 4 h of treatment, an increase in cellular metabolism was observed for all RISP concentrations, but emulsions did not change their metabolic rate, except at the highest concentration without drug (25 MUg/mL), which showed a significant reduction in metabolism respect to the control. Additionally, locomotor activity and heart rate in zebrafish were measured as parameters of in vivo toxicity. Only the highest concentration (0.625 MUg/mL) showed a cardiotoxic effect, which corresponds to the decrease in spontaneous movement observed previously. As all the materials contained in the formulations were US FDA approved, the NE selected would be good candidate for clinical trials. PMID- 26359784 TI - Carboxymethyl lysine, an advanced glycation end product, and incident diabetes: a case-cohort analysis of the ARIC Study. AB - AIMS: To verify whether elevated fasting levels of circulating carboxymethyl lysine (CML), an advanced glycation end product, predict the development of diabetes in middle-age adults. METHODS: Using a stratified case-cohort design, we followed 543 middle-aged individuals who developed diabetes and 514 who did not over a median 9 years in the Atherosclerosis Risk in Communities Study. Weighted Cox proportional hazards analyses were used to account for the design. RESULTS: In weighted analyses, correlation between CML levels and anthropometric, inflammatory or metabolic variables was minimal (Pearson correlations usually < 0.10). CML, when modelled as a continuous variable and after adjustment for age, sex, race, centre, parental history of diabetes, BMI, waist-to-hip ratio, non esterified fatty acids, oxidized LDL-cholesterol, GFR, smoking, an inflammation score, adiponectin, leptin, insulin and glucose levels, was associated with an increased risk of diabetes [Hazard ratio (HR) = 1.35; 95% confidence interval (CI) 1.09-1.67, for each 100 ng/ml CML increment]. Baseline glucose level and race each modified the association (P < 0.05 for interaction), which was present only among those with impaired fasting glucose (>= 5.6 mmol/l, HR = 1.61, 95% CI 1.26-2.05) and among white participants (HR = 1.50, 95% CI 1.13-1.99). CONCLUSIONS: Elevated fasting CML, after adjustment for multiple risk factors for diabetes, predicts the development of incident diabetes, the association being present among those with impaired fasting glucose and in white participants. These prospective findings suggest that advanced glycation end products might play a role in the development of diabetes. PMID- 26359785 TI - Drinking and mortality: long-term follow-up of drinking-discordant twin pairs. AB - AIMS: To determine if associations of alcohol consumption with all-cause mortality replicate in discordant monozygotic twin comparisons that control for familial and genetic confounds. DESIGN: A 30-year prospective follow-up. SETTING: Population-based older Finnish twin cohort. PARTICIPANTS: Same-sex twins, aged 24 60 years at the end of 1981, without overt comorbidities, completed questionnaires in 1975 and 1981 with response rates of 89 and 84%. A total of 15,607 twins were available for mortality follow-up from the date of returned 1981 questionnaires to 31 December 2011; 14,787 twins with complete information were analysed. MEASUREMENTS: Self-reported monthly alcohol consumption, heavy drinking occasions (HDO) and alcohol-induced blackouts. Adjustments for age, gender, marital and smoking status, physical activity, obesity, education and social class. FINDINGS: Among twins as individuals, high levels of monthly alcohol consumption (>= 259 g/month) associated with earlier mortality [hazard ratio (HR) = 1.63, 95% confidence interval (CI) = 1.47-1.81]. That association was replicated in comparisons of all informatively drinking-discordant twin pairs (HR = 1.91, 95% CI = 1.49-2.45) and within discordant monozygotic (MZ) twin pairs (HR = 2.24, 95% CI = 1.31-3.85), with comparable effect size. Smaller samples of MZ twins discordant for HDO and blackouts limited power; a significant association with mortality was found for multiple blackouts (HR = 2.82, 95% CI = 1.30-6.08), but not for HDO. CONCLUSIONS: The associations of high levels of monthly alcohol consumption and alcohol-induced blackouts with increased all cause mortality among Finnish twins cannot be explained by familial or genetic confounds; the explanation appears to be causal. PMID- 26359786 TI - Intracellular Distribution and Involvement of GPR30 in the Actions of E2 on C2C12 Cells. AB - G-protein-coupled receptor 30 (GPR30) is an estrogen receptor that initiates several rapid, non-genomic signaling events triggered by E2. GPR30 has recently been identified in C2C12 cells; however, little is known about the intracelular distribution and its role in C2C12 myoblasts and myotubes. By western blotting and immunohistochemistry, we evidenced expression of GPR30. While in C2C12 myoblasts, the receptor was present in nucleus, mitochondria, and endoplasmic reticulum, in C2C12 myotubes, it was additionally found in cytoplasm. Using trypan blue uptake assay to determine cellular death and fluorescent microscopy to evaluate picnotic nuclei and mitochondrial distribution, we demonstated that treatment of C2C12 myoblasts with G1 (GPR30 agonist) did not protect the cells against apoptosis induced by H2O2 as E2. However, when G15 (GPR30 antagonist) was used, E2 could not prevent the damage caused by the oxidative stress. Further, some of the molecular mechanisms involved were investigated by wertern blot assays. Thus, E2 was able to induce AKT phosphorylation in apoptotic conditions and ERK phosphorylation in proliferating C2C12 cells but not when the cultures were incubated with G15. Additionally, using G15 antagonist we have found that GPR30 participates in the myogenin expression and creatine kinase activity stimulated by E2 in the first steps of C2C12 differentiation. Althogether these findings provide evidences showing that GPR30 is expressed in diverse intracellular compartments in undifferentiated and differentiated C2C12 cells and mediates E2 actions. PMID- 26359788 TI - Pd(II) -Catalyzed Intermolecular Amination of Unactivated C(sp(3) )-H Bonds. AB - Pd(II) -catalyzed intermolecular amination of unactivated C(sp(3) )-H bonds has been successfully developed for the first time. This method provides a new way to achieve the challenging intermolecular amination of unactivated C(sp(3) )-H bonds, producing a variety of unnatural beta(2) -amino carboxylic acid analogues. This C(sp(3) )-H amination protocol is demonstrated with a broad substrate scope, good functional-group tolerance, and chemoselectivity. It is operated without use of phosphine ligand or external oxidant. PMID- 26359787 TI - Functional impairment in older liver transplantation candidates: From the functional assessment in liver transplantation study. AB - The emerging epidemic of older patients with cirrhosis has led to a sharp increase in the number of >=65 year olds considering liver transplantation (LT). However, clinicians lack objective measures to risk stratify older patients. We aimed to determine whether the short physical performance battery (SPPB), a well validated geriatric measure of physical function, has greater prognostic value in older versus younger LT candidates. Adult outpatients listed for LT with laboratory Model for End-Stage Liver Disease score >= 12 underwent physical function testing using the SPPB, consisting of gait speed, chair stands, and balance. Patients were categorized by age ("younger," < 65 years; "older," >= 65 years) and SPPB ("impaired," <= 9; "robust," > 9). Competing risks models associated age and SPPB with wait-list death/delisting. Of 463 LT candidates, 21% were >= 65 years and 18% died or were delisted. Older patients had slower gait (1.1 versus 1.3 m/seconds; P < 0.001), a trend of slower chair stands (12.8 versus 11.8 seconds; P = 0.06), and a smaller proportion able to complete all balance tests (65% versus 78%; P = 0.01); SPPB was lower in older versus younger patients (10 versus 11; P = 0.01). When compared to younger robust patients as a reference group, younger impaired patients (hazard ratio [HR], 1.77; P = 0.03) and older impaired patients (HR, 2.70; P = 0.003) had significantly higher risk of wait-list mortality, but there was no difference in risk for older robust patients (HR 1.38; P = 0.35) [test of equality, P = 0.01]. After adjustment for Model for End-Stage Liver Disease-sodium (MELD-Na) score, only older impaired patients had an increased risk of wait-list mortality compared to younger robust patients (HR, 2.36; P = 0.01; test of equality P = 0.05). In conclusion, functional impairment, as assessed by the SPPB, predicts death/delisting for LT candidates >=65 years independent of MELD-Na. Further research into activity based interventions to reduce adverse transplant outcomes in this population is warranted. PMID- 26359789 TI - Molecular modeling and multi-spectroscopic approaches to study the interaction between antibacterial drug and human immunoglobulin G. AB - Mechanistic and conformational studies on the interaction of sulfamethoxazole (SMX) with human immunoglobulin G (HIgG) were performed by molecular modeling and multi-spectroscopic methods. The interaction mechanism was firstly predicted through molecular modeling that confirmed the interaction between SMX and HIgG. The binding parameters and thermodynamic parameters at different temperatures had been calculated according to the Stern-Volmer, Scatchard, Sips and Van 't Hoff equations, respectively. Experimental results showed that the fluorescence intensity of HIgG was quenched by the gradual addition of SMX. The binding constants of SMX with HIgG decreased with the increase of temperature, which meant that the quenching mechanism was a static quenching. Meanwhile, the results also confirmed that there was one independent class of binding site on HIgG for SMX during their interaction. The thermodynamic parameters of the reaction, namely standard enthalpy DeltaH(0) and entropy DeltaS(0), had been calculated to be -14.69 kJ.mol(-1) and 22.99 J.mol(-1) .K(-1), respectively, which suggested that the electrostatic and hydrophobic interactions were the predominant intermolecular forces in stabilizing the SMX-HIgG complex. Furthermore, experimental results obtained from three-dimensional fluorescence spectroscopy, UV-vis absorption spectroscopy and circular dichroism (CD) spectroscopy confirmed that the conformational structure of HIgG was altered in the presence of SMX. PMID- 26359790 TI - Oxidative stress by inorganic nanoparticles. AB - Metallic and metallic oxide nanoparticles (NPs) have been increasingly used for various bio-applications owing to their unique physiochemical properties in terms of conductivity, optical sensitivity, and reactivity. With the extensive usage of NPs, increased human exposure may cause oxidative stress and lead to undesirable health consequences. To date, various endogenous and exogenous sources of oxidants contributing to oxidative stress have been widely reported. Oxidative stress is generally defined as an imbalance between the production of oxidants and the activity of antioxidants, but it is often misrepresented as a single type of cellular stress. At the biological level, NPs can initiate oxidative stress directly or indirectly through various mechanisms, leading to profound effects ranging from the molecular to the disease level. Such effects of oxidative stress have been implicated owing to their small size and high biopersistence. On the other hand, cellular antioxidants help to counteract oxidative stress and protect the cells from further damage. While oxidative stress is commonly known to exert negative biological effects, measured and intentional use of NPs to induce oxidative stress may provide desirable effects to either stimulate cell growth or promote cell death. Hence, NP-induced oxidative stress can be viewed from a wide paradigm. Because oxidative stress is comprised of a wide array of factors, it is also important to use appropriate assays and methods to detect different pro oxidant and antioxidant species at molecular and disease levels. WIREs Nanomed Nanobiotechnol 2016, 8:414-438. doi: 10.1002/wnan.1374 For further resources related to this article, please visit the WIREs website. PMID- 26359791 TI - The unification of physics: the quest for a theory of everything. AB - The holy grail of physics has been to merge each of its fundamental branches into a unified "theory of everything" that would explain the functioning and existence of the universe. The last step toward this goal is to reconcile general relativity with the principles of quantum mechanics, a quest that has thus far eluded physicists. Will physics ever be able to develop an all-encompassing theory, or should we simply acknowledge that science will always have inherent limitations as to what can be known? Should new theories be validated solely on the basis of calculations that can never be empirically tested? Can we ever truly grasp the implications of modern physics when the basic laws of nature do not always operate according to our standard paradigms? These and other questions are discussed in this paper. PMID- 26359792 TI - Clinical analysis of childhood intermittent exotropia with surgical success at postoperative 2 years. AB - PURPOSE: To analyse the characteristics of children who had maintained the successful outcome at 2 years after surgery for intermittent exotropia. METHODS: A retrospective study was performed in 216 patients who had undergone intermittent exotropia surgery and had had at least 2 years of follow-up. Surgical outcomes were grouped, according to the angle of deviation at postoperative 2 years, as success (esophoria/tropia <= 5 prism dioptres (PD) to exophoria/tropia <= 10PD), recurrence (exotropia > 10PD or reoperation within 2 years) or overcorrection (esophoria/tropia > 5PD). We investigated various clinical factors for their possible associations with the surgical outcomes. RESULTS: Of the 216 patients, 128 (59%) were assigned to the success group, and 84 (39%) to the recurrence group. According to a univariate analysis, surgical method and the angle of deviation at the postoperative day 1 showed statistically significant associations with the surgical outcome for intermittent exotropia. However, in the results of a logistic regression test, the angle of deviation at distance at postoperative day 1 was the only factor showing a significant association (p = 0.023). CONCLUSIONS: Early postoperative overcorrection was significantly associated with the maintenance of successful surgical outcome of intermittent exotropia at postoperative 2 years. PMID- 26359793 TI - When Is Structure, Function? Revisiting an Old Concept in Atrial Fibrillation. PMID- 26359794 TI - Smoking and Its Association With Morbidity in Systemic Lupus Erythematosus Evaluated by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index: Preliminary Data and Systematic Review. AB - OBJECTIVE: Due to the increased availability of effective treatments, patients with systemic lupus erythematosus (SLE) now have longer survival times, and factors involved in cumulative chronic damage in SLE need to be better understood. This study was undertaken to evaluate the relationship between smoking and cumulative chronic damage in SLE patients. METHODS: A cross-sectional study of SLE patients was performed to investigate the possible association between smoking exposure (ever [previous or current, active or secondhand smokers] or never) and cumulative chronic damage as measured by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). A systematic review of the literature was conducted by cross searching Medline for the terms lupus and smoking. RESULTS: We enrolled 105 patients with SLE (96% female), with a mean +/- SD age of 40.7 +/- 11.4 years and a mean followup time of 8.98 years. Of the 105 patients, 74 had an SDI score of 1 10, and 31 had an SDI score of 0. The difference between smoking exposure and no smoking exposure was significant (P = 0.02 by chi-square test in contingency table analysis), and SLE patients who were never exposed to smoking had 0.78 times the risk of progressing toward a cumulative damage status (SDI score of > 0) (95% confidence interval 0.16-0.98) throughout the followup period compared to those who were ever exposed. In the systematic review of the literature, we found only a small number of articles that addressed some aspects of the relationship between smoking exposure and cumulative damage in SLE patients. CONCLUSION: Our findings indicate that smoking exposure is associated with cumulative chronic damage, as determined by the SDI score, in patients with SLE. Smoking exposure may have deleterious effects on lupus morbidity, and more detailed studies of this association are needed. PMID- 26359795 TI - Benzo(a)pyrene inhibits migration and invasion of extravillous trophoblast HTR 8/SVneo cells via activation of the ERK and JNK pathway. AB - Benzo(a)pyrene (BaP) is a persistent organic pollutant (POP) that is a serious threat to human health. Numerous studies have shown that BaP causes adverse effects in pregnancy, but the mechanism remains unclear. The moderate invasion of trophoblast cells into the endometrium is an important factor during successful embryo implantation. The aim of this study was to investigate the effect and mechanism of BaP on the invasion and migration of trophoblast cells. HTR-8/SVneo cells were treated with different concentrations (1, 5, 10, 25, 50 and 100 MUM) of BaP. The invasion and migration of HTR-8/SVneo cells were observed after BaP treatment. The protein levels related to migration and invasion was detected by Western blot. The results confirmed that BaP inhibits the migration and invasion of extravillous trophoblast HTR-8/SVneo cells. Further investigations indicated that the protein levels of MMP-2, MMP-9 and E-cadherin in HTR-8/SVneo cells were changed by BaP treatment. Moreover, the data demonstrated that BaP activated the MAPK signaling pathway. Pretreatment with specific inhibitors of MAPK rescued BaP induced change in the migration and invasion of HTR-8/SVneo cells. Taken together, our results indicated that BaP inhibits invasion and the migration of HTR-8/SVneo cells, which might cause a failure in early pregnancy. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26359796 TI - Targeting MicroRNAs in Prevention and Treatment of Neurodegenerative Disorders. AB - Preclinical Research microRNAs (miRNAs) are small noncoding RNAs (ncRNAs) that are key regulators of gene expression. They act on wide range of targets by binding to mRNA via imperfect complementarity at 3' UTR. Evidence suggests that miRNAs regulate many biological processes including neuronal development, differentiation, and disease. Altered expression of several miRNAs has been reported in many neurodegenerative disorders (NDDs). Many miRNAs are altered in these diseases, but miRNA 15, miRNA 21, and miRNA 146a have been shown to play critical role in many neurodegenerative conditions. As these miRNAs regulate many genes, miRNA targeted approaches would allow concurrently targeting of multiple effectors of pathways that regulate disease progression. In this review, we describe the role of miRNAs in various NDDs and their potential as therapeutic tools in prevention and treatment of neurological conditions. PMID- 26359797 TI - A Parameterization of Cholesterol for Mixed Lipid Bilayer Simulation within the Amber Lipid14 Force Field. AB - The Amber Lipid14 force field is expanded to include cholesterol parameters for all-atom cholesterol and lipid bilayer molecular dynamics simulations. The General Amber and Lipid14 force fields are used as a basis for assigning atom types and basic parameters. A new RESP charge derivation for cholesterol is presented, and tail parameters are adapted from Lipid14 alkane tails. 1,2 Dimyristoyl-sn-glycero-3-phosphocholine (DMPC), 1,2-dioleoyl-sn-glycero-3 phosphocholine (DOPC), and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayers are simulated at a range of cholesterol contents. Experimental bilayer structural properties are compared with bilayer simulations and are found to be in good agreement. With this parameterization, another component of complex membranes is available for molecular dynamics with the Amber Lipid14 force field. PMID- 26359798 TI - Brain structural and functional connectivity in Parkinson's disease with freezing of gait. AB - OBJECTIVE: To use a multimodal approach to assess brain structural pathways and resting state (RS) functional connectivity abnormalities in patients with Parkinson's disease and freezing of gait (PD-FoG). METHODS: T1-weighted, diffusion tensor (DT) MRI and RS functional MRI (fMRI) were obtained from 22 PD FoG patients and 35 controls on a 3.0 T MR scanner. Patients underwent clinical, motor, and neuropsychological evaluations. Gray matter (GM) volumes and white matter (WM) damage were assessed using voxel based morphometry and tract-based spatial statistics, respectively. The pedunculopontine tract (PPT) was studied using tractography. RS fMRI data were analyzed using a model free approach investigating the main sensorimotor and cognitive brain networks. Multiple regression models were performed to assess the relationships between structural, functional, and clinical/cognitive variables. Analysis of GM and WM structural abnormalities was replicated in an independent sample including 28 PD-FoG patients, 25 PD patients without FoG, and 30 healthy controls who performed MRI scans on a 1.5 T scanner. RESULTS: Compared with controls, no GM atrophy was found in PD-FoG cases. PD-FoG patients showed WM damage of the PPT, corpus callosum, corticospinal tract, cingulum, superior longitudinal fasciculus, and WM underneath the primary motor, premotor, prefrontal, orbitofrontal, and inferior parietal cortices, bilaterally. In PD-FoG, right PTT damage was associated with a greater disease severity. Analysis on the independent PD sample showed similar findings in PD-FoG patients relative to controls as well as WM damage of the genu and body of the corpus callosum and right parietal WM in PD-FoG relative to PD no FoG patients. RS fMRI analysis showed that PD-FoG is associated with a decreased functional connectivity of the primary motor cortex and supplementary motor area bilaterally in the sensorimotor network, frontoparietal regions in the default mode network, and occipital cortex in the visual associative network. CONCLUSIONS: This study suggests that FoG in PD can be the result of a poor structural and functional integration between motor and extramotor (cognitive) neural systems. PMID- 26359799 TI - Effects of simulated microgravity on the expression of presynaptic proteins distorting the GABA/glutamate equilibrium--A proteomics approach. AB - Microgravity may cause cognition-related changes in the animal nervous system due to the resulting uneven flow of fluids in the body. These changes may restrict the long-term stay of humans in space for various purposes. In this study, a rat tail suspension model (30 degrees ) was used to explore the effects of 21 days of prolonged simulated microgravity (SM) on the expression of proteins involved in cognitive functions in the rat hippocampus. SM decreased the content of gamma aminobutyric acid (GABA) and increased the content of glutamate (Glu) in the rat hippocampus. A comparative (18)O-labeled quantitative proteomics strategy was applied to detect the differential expression of synaptic proteins under SM. Fifty-three proteins were found to be differentially expressed under SM. Microgravity induces difficulty in the formation of the SNARE complex due to the down-regulation of vesicle-associated membrane protein 3(VAMP3) and syntaxin-1A. Synaptic vesicle recycling may also be affected due to the dysregulation of syntaxin-binding protein 5 (tomosyn), rab3A and its effector rim2. Both processes are disturbed, indicating that presynaptic proteins mediate a GABA/Glu imbalance under SM. These findings provide clues for understanding the mechanism of the GABA/Glu equilibrium in the hippocampus induced by microgravity in space and represent steps toward safe space travel. PMID- 26359800 TI - Introduction to the ICBEB Special Focus. PMID- 26359801 TI - Production of Long-Chain alpha,omega-Dicarboxylic Acids by Engineered Escherichia coli from Renewable Fatty Acids and Plant Oils. AB - Long-chain alpha,omega-dicarboxylic acids (LDCAs, >= C12) are widely used as a raw material for preparing various commodities and polymers. In this study, a CYP450-monooxygenase-mediated omega-oxidation pathway system with high omega regioselectivity was heterologously expressed in Escherichia coli to produce DCAs from fatty acids. The resulting engineered E. coli produced a maximum of 41 mg/L of C12 DCA and 163 mg/L of C14 DCA from fatty acids (1 g/L), following 20 h of whole cell biotransformation. Addition of a heme precursor and the hydroxyl radical scavenger, thiourea, increased product concentration (159 mg/L of C12 DCA and 410 mg/L of C14 DCA) in a shorter culture duration than that of the corresponding controls. DCAs of various chain lengths were synthesized from coconut oil hydrolysate using the engineered E. coli. This novel synthetic biocatalytic system could be applied to produce high value DCAs in a cost effective manner from renewable plant oils. PMID- 26359802 TI - CXCL13 and CCL11 Serum Levels and Lymphoma and Disease Activity in Primary Sjogren's Syndrome. AB - OBJECTIVE: Non-Hodgkin's lymphoma (NHL) is a severe complication of primary Sjogren's syndrome (SS). Ectopic germinal centers (GCs) in the salivary glands are predictors of the occurrence of NHL. Given the association between CCL11 and CXCL13 and ectopic GCs, we assessed the link between these chemokines and NHL, as well as the association between these chemokines and disease activity, in patients with primary SS. METHODS: Serum levels of CCL11 and CXCL13 were evaluated by multiplex assay in 385 patients included in the Assessment of Systemic Signs and Evolution of Sjogren's Syndrome (ASSESS) cohort. The association between chemokine levels, B cell biomarkers, and patient subsets was assessed using Spearman's test for continuous data and the nonparametric Mann Whitney U test for categorical data. Multivariate analyses were performed to identify parameters associated with lymphoma and disease activity. RESULTS: Seventeen patients had a history of lymphoma, and 5 of them had developed NHL during followup. The median serum levels of CCL11 and CXCL13 in the total cohort were 106.48 pg/ml (interquartile range 69.33-149.85) and 108.31 pg/ml (interquartile range 58.88-200.13), respectively. Patients with lymphoma had higher levels of CXCL13 than did patients without lymphoma (P = 0.006) and a trend toward a higher level of CCL11 (P = 0.056). Low C4 and high BAFF levels were associated with NHL on multivariate analysis (P = 0.01 and P = 0.0002, respectively). CCL11 and CXCL13 levels correlated positively with the rheumatoid factor titer, the kappa-to-lambda free light chain ratio, and the beta2 microglubulin level. CXCL13 was the only parameter associated with disease activity on multivariate analysis. CONCLUSION: These findings demonstrate a link between CXCL13 and CCL11 and disease activity and lymphoma. This highlights the continuum between chronic B cell activation, disease activity, and lymphomagenesis in patients with primary SS. PMID- 26359803 TI - Pseudomonoamniotic Pregnancy: Case Report and Review of Etiologic Considerations. AB - Pseudomonoamniotic gestations are increasingly recognized through sonographic surveillance of monochorionic twins, though etiologic factors remain undefined. We present a case of spontaneous pseudomonoamniotic twins and propose umbilical cord insertion proximity as a sonographic marker. Systematic review of the literature was performed and additional cases with similar findings were noted. Approximately 75% of reported cases (28/37) were deemed spontaneous and several included short inter-cord distances. Shunting of blood away from the membranes in the region between the cord insertions may be responsible for membrane rupture. Further investigation is needed into short inter-cord distance as a marker for monochorionic twins at risk to become a pseudomonoamniotic gestation. PMID- 26359805 TI - Tier-specific evolution of match performance characteristics in the English Premier League: it's getting tougher at the top. AB - This study investigated the evolution of physical and technical performances in the English Premier League (EPL), with special reference to league ranking. Match performance observations (n = 14,700) were collected using a multiple-camera computerised tracking system across seven consecutive EPL seasons (2006-07 to 2012-13). Final league rankings were classified into Tiers: (A) 1st-4th ranking (n = 2519), (B) 5th-8th ranking (n = 2965), (C) 9th-14th ranking (n = 4448) and (D) 15th-20th ranking (n = 4768). Teams in Tier B demonstrated moderate increases in high-intensity running distance while in ball possession from the 2006-07 to 2012-13 season (P < 0.001; effect size [ES]: 0.68), with Tiers A, C and D producing less pronounced increases across the same period (P < 0.005; ES: 0.26, 0.41 and 0.33, respectively). Large increases in sprint distance were observed from the 2006-07 to 2012-13 season for Tier B (P < 0.001; ES: 1.21), while only moderate increases were evident for Tiers A, C and D (P < 0.001; ES: 0.75, 0.97 and 0.84, respectively). Tier B demonstrated large increases in the number of passes performed and received in 2012-13 compared to 2006-07 (P < 0.001; ES: 1.32 1.53) with small-to-moderate increases in Tier A (P < 0.001; ES: 0.30-0.38), Tier C (P < 0.001; ES: 0.46-0.54) and Tier D (P < 0.001; ES: 0.69-0.87). The demarcation line between 4th (bottom of Tier A) and 5th ranking (top of Tier B) in the 2006-07 season was 8 points, but this decreased to just a single point in the 2012-13 season. The data demonstrate that physical and technical performances have evolved more in Tier B than any other Tier in the EPL and could indicate a narrowing of the performance gap between the top two Tiers. PMID- 26359804 TI - Species-specific action of (Pro3)GIP - a full agonist at human GIP receptors, but a partial agonist and competitive antagonist at rat and mouse GIP receptors. AB - BACKGROUND AND PURPOSE: Specific, high potency receptor antagonists are valuable tools when evaluating animal and human physiology. Within the glucose-dependent, insulinotropic polypeptide (GIP) system, considerable attention has been given to the presumed GIP receptor antagonist, (Pro3)GIP, and its effect in murine studies. We conducted a pharmacological analysis of this ligand including interspecies differences between the rodent and human GIP system. EXPERIMENTAL APPROACH: Transiently transfected COS-7 cells were assessed for cAMP accumulation upon ligand stimulation and assayed in competition binding using (125) I-human GIP. Using isolated perfused pancreata both from wild type and GIP receptor deficient rodents, insulin-releasing, glucagon-releasing and somatostatin releasing properties in response to species-specific GIP and (Pro3)GIP analogues were evaluated. KEY RESULTS: Human (Pro3)GIP is a full agonist at human GIP receptors with similar efficacy (Emax ) for cAMP production as human GIP, while both rat and mouse(Pro3)GIP were partial agonists on their corresponding receptors. Rodent GIPs are more potent and efficacious at their receptors than human GIP. In perfused pancreata in the presence of 7 mM glucose, both rodent (Pro3)GIP analogues induced modest insulin, glucagon and somatostatin secretion, corresponding to the partial agonist activities observed in cAMP production. CONCLUSIONS AND IMPLICATIONS: When evaluating new compounds, it is important to consider interspecies differences both at the receptor and ligand level. Thus, in rodent models, human GIP is a comparatively weak partial agonist. Human (Pro3)GIP was not an antagonist at human GIP receptors, so there is still a need for a potent antagonist in order to elucidate the physiology of human GIP. PMID- 26359806 TI - The Use and the Prescription Pattern of Traditional Chinese Medicine Among Urolithiasis Patients in Taiwan: A Population-Based Study. AB - OBJECTIVES: To investigate the pattern of Traditional Chinese Medicine (TCM) usage for urolithiasis patients in Taiwan and to determine the most common Chinese herbal products used for urolithiasis. DESIGN: Retrospective review of urolithiasis patients treated with TCM treatment. SETTINGS/LOCATION: One million randomly selected samples in the Taiwanese National Health Insurance Research Database between 1997 and 2008. PATIENTS: Eighty-two thousand five hundred and fifty-one newly diagnosed urolithiasis patients. OUTCOME MEASURES: The correlation between TCM treatment, demographic factors, or medical conditions. RESULTS: A total of 62.6% of urolithiasis patients use TCM treatment. A younger age, female gender, polypharmacy, multiple comorbidities, and stone in the lower urinary tract result in a greater tendency to use TCM, after adjusting for demographic factors. Jia-Wei-Xiao-Yao-San Extract Powder and Ji-Sheng-Shen-Qi-Wan Extract Powder are the most frequently prescribed Chinese medicine formulae. CONCLUSION: This is the first study to examine the use of and the prescription pattern for TCM in urolithiasis patients using a random, national population based sample. More than 62% of urolithiasis patients use TCM, and patients with polypharmacy, multiple comorbidities, and stone in the ureter are more likely to use TCM. The most frequently prescribed Chinese medicine formulae were Jia-Wei Xiao-Yao-San Extract Powder and Ji-Sheng-Shen-Qi-Wan Extract Powder, which were reported to retard the progression of renal failure and alleviate flank pain or tenderness. PMID- 26359807 TI - [Hospital disinfection challenges due to multiresistant pathogens in surgery]. AB - The number of antibiotic-resistant pathogens is increasing continuously while the development of new, effective antibiotics cannot be expected in the near future. Postoperative infections represent most of the nosocomial infections by now. Based on this, hygienic strategies regain importance, since a sustainable control of nosocomial infections will not succeed without the implementation of such strategies. In this article, the most important preventive strategies for prevention of infections with MRSA and 3- and 4-fold resistant gram-negative bacteria on the basis of current recommendations of the Commission for Hospital Hygiene and Infection Prevention (KRINKO) are presented. PMID- 26359808 TI - Geometrical and topological analysis of in vivo confocal microscopy images reveals dynamic maturation of epidermal structures during the first years of life. AB - Reflectance confocal microscopy is successfully used in infant skin research. Infant skin structure, function, and composition are undergoing a maturation process. We aimed to uncover how the epidermal architecture and cellular topology change with time. Images were collected from three age groups of healthy infants between one and four years of age and adults. Cell centers were manually identified on the images at the stratum granulosum (SG) and stratum spinosum (SS) levels. Voronoi diagrams were used to calculate geometrical and topological parameters. Infant cell density is higher than that of adults and decreases with age. Projected cell area, cell perimeter, and average distance to the nearest neighbors increase with age but do so distinctly between the two layers. Structural entropy is different between the two strata, but remains constant with time. For all ages and layers, the distribution of the number of nearest neighbors is typical of a cooperator network architecture. The topological analysis provides evidence of the maturation process in infant skin. The differences between infant and adult are more pronounced in the SG than SS, while cell cooperation is evident in all cases of healthy skin examined. PMID- 26359809 TI - Safety of cornea and iris in ocular surgery with 355-nm lasers. AB - A recent study showed that 355-nm nanosecond lasers cut cornea with similar precision to infrared femtosecond lasers. However, use of ultraviolet wavelength requires precise assessment of ocular safety to determine the range of possible ophthalmic applications. In this study, the 355-nm nanosecond laser was evaluated for corneal and iris damage in rabbit, porcine, and human donor eyes as determined by minimum visible lesion (MVL) observation, live/dead staining of the endothelium, and apoptosis assay. Single-pulse damage to the iris was evaluated on porcine eyes using live/dead staining. In live rabbits, the cumulative median effective dose (ED50) for corneal damage was 231 J/cm2, as seen by lesion observation. Appearance of endothelial damage in live/dead staining or apoptosis occurred at higher radiant exposure of 287 J/cm2. On enucleated rabbit and porcine corneas, ED50 was 87 and 52 J/cm2, respectively, by MVL, and 241 and 160 J/cm2 for endothelial damage. In human eyes, ED50 for MVL was 110 J/cm2 and endothelial damage at 453 J/cm2. Single-pulse iris damage occurred at ED 50 of 208 mJ/cm2. These values determine the energy permitted for surgical patterns and can guide development of ophthalmic laser systems. Lower damage threshold in corneas of enucleated eyes versus live rabbits is noted for future safety evaluation. PMID- 26359810 TI - Application of biospeckles for assessment of structural and cellular changes in muscle tissue. AB - A modified spatial-temporal speckle correlation technique for operational assessment of structural changes in muscle tissues after slaughtering is considered. Coefficient of biological activity as a quantitative indicator of structural changes of biochemical processes in biological tissues is proposed. The experimental results have shown that this coefficient properly evaluates the biological activity of pig and chicken muscle tissue samples. Studying the degradation processes in muscle tissue during long-time storage in a refrigerator by measuring the spatial-temporal dynamics of biospeckle patterns is carried out. The reduction of the bioactivity level of refrigerated muscle tissue samples connected with the initiation of muscle fiber cracks and ruptures, reduction of sarcomeres, nuclei deformation, nuclear chromatin diminishing, and destruction of mitochondria is analyzed. PMID- 26359811 TI - Development and investigation of a magnetic resonance imaging-compatible microlens-based optical detector. AB - A noncontact optical detector for in vivo imaging has been developed that is compatible with magnetic resonance imaging (MRI). The optical detector employs microlens arrays and might be classified as a plenoptic camera. As a resulting of its design, the detector possesses a slim thickness and is self-shielding against radio frequency (RF) pulses. For experimental investigation, a total of six optical detectors were arranged in a cylindrical fashion, with the imaged object positioned in the center of this assembly. A purposely designed RF volume resonator coil has been developed and is incorporated within the optical imaging system. The whole assembly was placed into the bore of a 1.5 T patient-sized MRI scanner. Simple-geometry phantom studies were performed to assess compatibility and performance characteristics regarding both optical and MR imaging systems. A bimodal ex vivo nude mouse measurement was conducted. From the MRI data, the subject surface was extracted. Optical images were projected on this surface by means of an inverse mapping algorithm. Simultaneous measurements did not reveal influences from the magnetic field and RF pulses onto optical detector performance (spatial resolution, sensitivity). No significant influence of the optical imaging system onto MRI performance was detectable. PMID- 26359812 TI - Hyperspectral imaging for detection of arthritis: feasibility and prospects. AB - Rheumatoid arthritis (RA) is a disease that frequently leads to joint destruction. It has a high incidence rate worldwide, and the disease significantly reduces patients' quality of life. Detecting and treating inflammatory arthritis before structural damage to the joint has occurred is known to be essential for preventing patient disability and pain. Existing diagnostic technologies are expensive, time consuming, and require trained personnel to collect and interpret data. Optical techniques might be a fast, noninvasive alternative. Hyperspectral imaging (HSI) is a noncontact optical technique which provides both spectral and spatial information in one measurement. In this study, the feasibility of HSI in arthritis diagnostics was explored by numerical simulations and optimal imaging parameters were identified. Hyperspectral reflectance and transmission images of RA and normal human joint models were simulated using the Monte Carlo method. The spectral range was 600 to 1100 nm. Characteristic spatial patterns for RA joints and two spectral windows with transmission were identified. The study demonstrated that transmittance images of human joints could be used as one parameter for discrimination between arthritic and unaffected joints. The presented work shows that HSI is a promising imaging modality for the diagnostics and follow-up monitoring of arthritis in small joints. PMID- 26359813 TI - Intraoperative laser speckle contrast imaging improves the stability of rodent middle cerebral artery occlusion model. AB - Rodent middle cerebral artery occlusion (MCAO) model is commonly used in stroke research. Creating a stable infarct volume has always been challenging for technicians due to the variances of animal anatomy and surgical operations. The depth of filament suture advancement strongly influences the infarct volume as well. We investigated the cerebral blood flow (CBF) changes in the affected cortex using laser speckle contrast imaging when advancing suture during MCAO surgery. The relative CBF drop area (CBF50, i.e., the percentage area with CBF less than 50% of the baseline) showed an increase from 20.9% to 69.1% when the insertion depth increased from 1.6 to 1.8 cm. Using the real-time CBF50 marker to guide suture insertion during the surgery, our animal experiments showed that intraoperative CBF-guided surgery could significantly improve the stability of MCAO with a more consistent infarct volume and less mortality. PMID- 26359814 TI - Efficacy of low-level laser therapy for the treatment of burning mouth syndrome: a randomized, controlled trial. AB - The aim of the present study was to assess the effect of low-level laser therapy (LLLT) in the treatment of burning mouth syndrome (BMS). A diode laser was used in 78 BMS patients who were randomly assigned into four groups: IR1W, n = 20 (830 nm, 100 mW, 5 J, 176 J/cm2, 50 s, LLLT weekly sessions, 10 sessions); IR3W, n = 20 (830 nm, 100 mW, 5 J, 176 J/cm2, 50 s, three LLLT weekly sessions, 9 sessions); red laser, n = 19 (685 nm, 35 mW, 2 J, 72 J/cm2, 58 s, three LLLT weekly sessions, 9 sessions); and control-group (CG), n = 19. Symptoms were assessed at the end of the treatment and eight weeks later; quality of life related to oral health was assessed using the Oral Health Impact Profile (OHIP 14). Statistical analysis was carried out using repeated measures analysis of variance followed by the posthoc Tukey test. There was significant reduction of the symptoms in all groups at the end of the treatment, which was maintained in the follow-up. The scores of the IR1W and IR3W laser groups differed significantly from those of the CG. There was also a decrease in the OHIP-14 scores in the four groups. The IR3W laser group scores differed significantly from those of the CG. LLLT reduces the symptoms of BMS and may be an alternative therapeutic strategy for the relief of symptoms in patients with BMS. PMID- 26359815 TI - New Targets for Temperature Management. PMID- 26359816 TI - MI to Cool? PMID- 26359817 TI - Multiple Stressors in a Changing World: The Need for an Improved Perspective on Physiological Responses to the Dynamic Marine Environment. AB - Abiotic conditions (e.g., temperature and pH) fluctuate through time in most marine environments, sometimes passing intensity thresholds that induce physiological stress. Depending on habitat and season, the peak intensity of different abiotic stressors can occur in or out of phase with one another. Thus, some organisms are exposed to multiple stressors simultaneously, whereas others experience them sequentially. Understanding these physicochemical dynamics is critical because how organisms respond to multiple stressors depends on the magnitude and relative timing of each stressor. Here, we first discuss broad patterns of covariation between stressors in marine systems at various temporal scales. We then describe how these dynamics will influence physiological responses to multi-stressor exposures. Finally, we summarize how multi-stressor effects are currently assessed. We find that multi-stressor experiments have rarely incorporated naturalistic physicochemical variation into their designs, and emphasize the importance of doing so to make ecologically relevant inferences about physiological responses to global change. PMID- 26359818 TI - Mechanisms of Physical-Biological-Biogeochemical Interaction at the Oceanic Mesoscale. AB - Mesoscale phenomena are ubiquitous and highly energetic features of ocean circulation. Their influence on biological and biogeochemical processes varies widely, stemming not only from advective transport but also from the generation of variations in the environment that affect biological and chemical rates. The ephemeral nature of mesoscale features in the ocean makes it difficult to elucidate the attendant mechanisms of physical-biological-biogeochemical interaction, necessitating the use of multidisciplinary approaches involving in situ observations, remote sensing, and modeling. All three aspects are woven through this review in an attempt to synthesize current understanding of the topic, with particular emphasis on novel developments in recent years. PMID- 26359819 TI - PET tracers for imaging brain alpha7 nicotinic receptors: an update. AB - Positron emission tomography (PET) molecular imaging of brain targets is a powerful tool to diagnose, follow up, and develop treatments and personalized medicine for a number of acute and chronic brain disorders. The availability of beta+ emitter tracers labelled with [(11)C] or [(18)F] having optimal characteristics of affinity and selectivity for alpha-7 nicotinic receptors (alpha7R) has received considerable attention, due to the major implication of these receptors in brain functions. The aim of this review is to identify the interest and need for the in vivo exploration of alpha7R by PET molecular imaging, which tools are currently available for this and how to progress. PMID- 26359820 TI - Addition of blood to a phycogenic bone substitute leads to increased in vivo vascularization. AB - The present study aimed to analyze the effects of the addition of blood to the phycogenic bone substitute Algipore((r)) on the severity of in vivo tissue reaction. Initially, Fourier-transform infrared spectroscopy (FTIR) of the bone substitute was conducted to analyze its chemical composition. The subcutaneous implantation model in Balb/c mice was then applied for up to 30 d to analyze the tissue reactions on the basis of specialized histochemical, immunohistochemical, and histomorphometrical methods. The data of the FTIR analysis showed that the phycogenic bone substitute material is mainly composed of hydroxyapatite with some carbonate content. The in vivo analyses revealed that the addition of blood to Algipore((r)) had a major impact on both angiogenesis and vessel maturation. The higher vascularization seemed to be based on significantly higher numbers of multinucleated TRAP-positive cells. However, mostly macrophages and a relatively low number of multinucleated giant cells were involved in the tissue reaction to Algipore((r)). The presented data show that the addition of blood to a bone substitute impacts the tissue reaction to it. In particular, the immune response and the vascularization were influenced, and these are believed to have a major impact on the regenerative potential of the process of bone tissue regeneration. PMID- 26359821 TI - Characterization of Magnetic Nanoparticles in Biological Matrices. AB - This Feature describes several methods for the characterization of magnetic nanoparticles in biological matrices such as cells and tissues. The Feature focuses on sample preparation and includes several case studies where multiple techniques were used in conjunction. PMID- 26359822 TI - Intravascular/Intralymphatic Histiocytosis: A Report of 3 Cases. AB - Intravascular/intralymphatic histiocytosis (IV/ILH) is a rare, reactive cutaneous condition, with uncertain pathogenesis. It may be associated with various inflammatory and neoplastic diseases. Although the clinical presentation is various, the biopsies reveal dilated vessels, mostly lymphatics, containing aggregates of histiocytes within their lumina. We described 3 cases of IV/ILH with different clinical presentations. In the first case, the patient presented with lymphedema in the genital region without any underlying disease. However, the second and third cases had reticular erythematous skin lesions. The second case had common variable immunodeficiency disease, rheumatoid arthritis, inflammatory bowel disease, and a history of a lymphoproliferative lesion. The third case had metal prostheses at both his right and left knees. In all these 3 cases, histopathologic and immunohistochemical findings were similar to each other and to those cases reported in the literature. In addition, the third case was admixed with reactive angioendotheliomatosis. In the second case, the endothelium of the ectatic vessels expressed CD31 and CD34, but not D2 40/podoplanin, pointing out that these vessels were blood vessels rather than lymphatics, differing from the other 2 cases. In conclusion, we believe, the most convincing statement about IV/ILH is that it is not a distinct clinicopathologic entity, but a histopathologic feature found as a part of a constellation of inflammatory changes or many other conditions. PMID- 26359823 TI - The Use of a Pediatric Migraine Practice Guideline in an Emergency Department Setting. AB - OBJECTIVE: The aim of the study was to evaluate the safety and efficacy of a standardized pediatric migraine practice guideline in the emergency department (ED). METHODS: Migraine Clinical Practice Guideline (MCPG) was created in collaboration with the Division of Pediatric Neurology and Pediatric Emergency Medicine. The MCPG was established on evidence-based data and best practice after a review of the literature. The MCPG was implemented for patients with a known diagnosis of migraine headaches and a verbal numeric pain score (VPS) greater than 6 on a 0 to 10 scale. Patients received intravenous saline, ketorolac, diphenhydramine, and either metoclopramide or prochlorperazine. After 40 minutes, another VPS was obtained, and if no improvement, a repeat dose of metoclopramide or prochlorperazine was administered. If after 40 minutes and minimal pain relief occurred, a consult to neurology was made. A chart review of patients enrolled in the MCPG from April 2004 to April 2013 was conducted. We recorded demographic data, vital signs, ED length of stay, initial VPS, last recorded VPS, adverse events, and admission rate. Nonparametric statistics were performed. RESULTS: A total of 533 charts were identified with a discharge diagnosis of migraine headache of which 266 were enrolled in the MCPG (179 females and 87 males). Mean (SD) age was 13.9 (3.1). Mean (SD) initial VPS was 7.8 (2.0). Mean (SD) discharge VPS was 2.1 (2.8), representing a 73% reduction of pain. Twenty patients (7.5%) were admitted for status migrainosus; mean (SD) age was 14.0 (3.5) years and mean (SD) VPS was 6.3 (2.8). Mean (SD) length of stay in ED was 283 (107) minutes. No adverse events were identified. CONCLUSIONS: Our MCPG was clinically safe and effective in treating children with acute migraine headaches. Our data add to the dearth of existing published literature on migraine treatment protocols in the ED setting. We recommend additional prospective and comparative studies to further evaluate the effectiveness of our protocol in this patient population. PMID- 26359824 TI - The Comparison of Accidental Poisonings Between Pharmaceuticals and Nonpharmaceuticals in Children Younger than 3 Years. AB - INTRODUCTION: The management of pediatric poisoning is dependent on the type of toxicant ingested; however, little information has been published regarding the difference in poisoning by pharmaceuticals and nonpharmaceuticals in children. We compared the accidental poisoning of children younger than 3 years who had ingested pharmaceuticals or nonpharmaceuticals using emergency medical information center data. METHODS: We retrospectively reviewed the records of the poisonings of children younger than 3 years who were evaluated by the Seoul Emergency Medical Information Center in 2011. The demographic data and detailed information regarding the poisonings were investigated. The substances that caused the poisonings were divided into the following 2 groups: pharmaceuticals and nonpharmaceuticals, and their characteristics and the differences between the 2 types of poisonings were investigated. RESULTS: A total of 1279 cases were collected, most of which involved children who were 13 to 24 months old. Boys (51.3%) were involved more than girls. Exposure to nonpharmaceuticals (60.7%) was more common than exposure to pharmaceuticals. Personal care products and respiratory agents were the most commonly implicated substances. There were several significant differences between the pharmaceutical and nonpharmaceutical groups. Poisoning by pharmaceuticals occurred more frequently in older children and more frequently at night. Although the exact exposure of the children in the pharmaceutical group was known and they required more treatment in the emergency department, they were not given extra immediate first aid than the children in the nonpharmaceutical group. CONCLUSIONS: Because there were several significant differences in the characteristics of accidental pediatric poisonings between the pharmaceutical and nonpharmaceutical groups, preventive strategies and educational programs should be implemented on the basis of the causative agent. PMID- 26359825 TI - Factors Associated With Discharge After Initial Emergency Treatment of Pediatric Migraine. AB - OBJECTIVE: Migraine treatment varies widely in the pediatric emergency department (ED). Factors associated with discharge after only initial emergency treatment were examined. METHODS: A retrospective chart analysis was conducted on patients 6 to 18 years old who presented to the St. Louis Children's Hospital ED between January 1, 2008, and December 31, 2011, with a discharge diagnosis of migraine (n = 700 visits). Associations between patient characteristics, initial treatments, and rates of discharge after only initial treatment were examined using a generalized linear model and receiver operating characteristic curves. RESULTS: If exclusively oral or intranasal (PO/IN) medications were given initially (n = 285), ibuprofen alone was associated with lower discharge rates compared with other PO/IN medication regimens (P < 0.05). The only other variable associated with discharge was arrival pain score (P < 0.05). When ibuprofen alone was administered, pain scores equal to or lower than 5/10 were associated with the greatest sensitivity and specificity for discharge. With administration of other PO/IN regimens, pain scores equal to or lower than 8/10 were associated with the greatest sensitivity and specificity for discharge. If intravenous (IV) medications were given initially (n = 415), ketorolac given with an antinausea medication was associated with higher discharge rates compared with independent administration of these medications (P < 0.05). Intravenous medications were associated with higher discharge rates compared with PO/IN medications (P < 0.001). CONCLUSIONS: Arrival pain score may be used to help select initial migraine treatment in the pediatric ED. Initial use of PO/IN regimens including triptans or an antiemetic and concurrent administration of IV ketorolac with an antiemetic may be associated with higher rates of discharge after initial treatment alone. PMID- 26359826 TI - A New Paradigm for the Management of Thoracolumbar Pediatric Spine Traumas. AB - OBJECTIVES: The transient breath holding sign (TBHS) is a clinical sign often associated with magnetic resonance imaging (MRI) spine traumatic lesions. The aims of this study were to prospectively evaluate the TBHS in the detection of thoracolumbar lesions in a large cohort of children and to establish a comprehensive strategy on the use of MRI in spine traumas in children. STUDY DESIGN: All conscious 5- to 16-year-old patients admitted for a spine trauma in our institution were prospectively included in the study. All patients were asked for the TBHS and underwent a full spine MRI. Sensitivity and specificity of the TBHS were derived from the confusion matrix. All MRI lesions were analyzed and classified. RESULTS: One hundred ninety-eight patients were included. The sensitivity of the TBHS was 92%, the specificity was 83%, the positive predictive value was 83%, and the negative predictive value was 91%. The x-rays missed 67% of the vertebrae injured in the MRI. The MRI lesions consisted in an upper end plate injury, in the sagittal plane only, in 90% of the cases. The vertebral canal and the spinal cord were never injured. CONCLUSIONS: This study confirms that the TBHS is a relevant clinical tool that should be added in the routine questionnaire after any trauma at admission. Magnetic resonance imaging should be restricted to patients with a TBHS positive at admission. A single T2 Short T1 Inversion Recovery (STIR) sagittal sequence seems sufficient to make the diagnosis and could replace the use of standard x-rays in pediatric spine traumas. PMID- 26359827 TI - If You Twinkle When You Tinkle, Stones Are Found on Ultrasound. AB - Urolithiasis in children is an underrecognized cause of pediatric abdominal pain. Our case describes a child who presented to the emergency department with right lower quadrant pain, in whom a point-of-care ultrasound detected an ureterovesicular stone, which obviated the need for any further radiographic studies. We review the current literature on pediatric urolithiasis with a focus on sonographic diagnosis. PMID- 26359828 TI - ACSM Clinician Profile. PMID- 26359829 TI - Deaths in Athletes: News on Hyponatremia, Nuances in Sickle Cell Trait. PMID- 26359831 TI - Rethinking the Cause of Exercise-Associated Muscle Cramping: Moving beyond Dehydration and Electrolyte Losses. PMID- 26359832 TI - Peripheral Nerve Injury. PMID- 26359833 TI - Five Key Characteristics to Consider when Purchasing a Running Shoe. PMID- 26359834 TI - Heterotopic Ossification after Acromioclavicular Separation in an Adolescent: A Case Report. PMID- 26359835 TI - Snapping Pes Syndrome in a Pediatric Athlete. PMID- 26359836 TI - Popliteal Artery Entrapment Syndrome. AB - Popliteal artery entrapment syndrome (PAES) may be implicated as a cause of lower leg pain in active individuals. Though a relatively rare syndrome, it is likely underdiagnosed. History often includes exertional lower leg pain, cramping, and/or paresthesias rather quickly relieved by rest, though examination may be benign. When suspected, imaging is recommended to assess anatomic variations versus functional entrapment of the artery in the calf. Because there are a number of diagnostic modalities available, it seems prudent to begin with noninvasive testing, such as ultrasound with Doppler and provocative maneuvers. Thereafter, advanced imaging (magnetic resonance imaging/magnetic resonance angiography) or arteriography may help identify a specific anatomic obstruction. Once confirmed, surgical exploration has historically been the treatment of choice, though less invasive interventions have been proposed. Though most patients reportedly return to high-level training, decision-making remains highly individualized. Further study of younger, active individuals with PAES will help to further define these criteria. PMID- 26359837 TI - Anatomic Factors that May Predispose Female Athletes to Anterior Cruciate Ligament Injury. AB - Female athletes are 2 to 10 times more likely to injure their anterior cruciate ligaments (ACL) than male athletes. There has been greater recognition of this gender discrepancy because female participation in competitive athletics has increased. Previous investigators have divided risk factors into hormonal, neuromuscular response, and anatomic subgroups. Gender variation within these groups may help explain the higher incidence of ACL injury in women. The purpose of this article is to review research examining female-specific anatomy that may predispose women to ACL injury. Specifically, we discuss how women may have increased tibial and meniscal slopes, narrower femoral notches, and smaller ACL, which may place the ACL at risk from injury. These anatomic factors, combined with other female-specific risk factors, may help physicians and researchers better understand why women appear to be more prone to ACL injury. PMID- 26359838 TI - Hip Pain in Athletes - When It is Not the Labrum. AB - Hip pain is a relatively common complaint in sports. It is tempting to blame the athlete's symptoms on labral pathology. However, there is a high incidence of asymptomatic labral disease. Therefore, even when a labral tear is present, it may not be the underlying cause of the patient's pain. Clinicians should familiarize themselves with the large differential diagnosis for hip and pelvis pain to include nonmusculoskeletal pathology. This article reviews nonlabral causes of hip pain in athletes. For ease of classification, the hip is divided into anterior, lateral, and posterior regions. PMID- 26359839 TI - Chronic Exertional Compartment Syndrome Testing. AB - Chronic exertional compartment syndrome is diagnosed based on historical and physical exam findings combined with elevated intracompartmental pressures. Direct static testing with a large bore needle device is the most common instrument used for diagnosis. Based on the most recent systematic reviews, there is poor evidence for the traditional diagnostic pressures used in practice with no standardization of the procedure. New research has introduced a standardized approach with dynamic testing of the limb with transducer-tipped catheters. Less invasive methods of testing using radiologic techniques are currently under investigation. A detailed understanding of the anatomy and physiology of the limb is paramount in executing a safe and accurate procedure. PMID- 26359840 TI - Subchondral Fracture of the Femoral Head in a High School Badminton Player: A Case Report. PMID- 26359841 TI - Medical Care of the Aquatics Athlete. AB - Competitive swimmers are affected by several musculoskeletal and medical complaints that are unique to the sport. 'Swimmer's shoulder,' the most common overuse injury, is usually caused by some combination of impingement, rotator cuff tendinopathy, scapular dyskinesis, and instability. The condition may be treated with training modifications, stroke error correction, and strengthening exercises targeting the rotator cuff, scapular stabilizers, and core. Implementation of prevention programs to reduce the prevalence of shoulder pathology is crucial. Knee pain usually results from the breaststroke kick in swimmers, and the 'egg beater' kick in water polo players and synchronized swimmers. Lumbar back pain also is common in aquatics athletes. Among the medical conditions of particular importance in swimmers are exercise-induced bronchoconstriction, respiratory illnesses, and ear problems. Participants in other aquatics sports (water polo, diving, synchronized swimming, and open water swimming) may experience medical ailments specific to the sport. PMID- 26359842 TI - Caring for Climbers. AB - Caring for climbers can be a challenge and requires familiarity with the distinctive mechanisms of common climbing injuries. Injuries such as climber's finger, climber's elbow, extensor hood syndrome, lateral collateral ligamentous injuries from climbing overload, and posttraumatic osteochondritis dissecans, among others, cannot be diagnosed if the practitioner does not have a specialized knowledge of the sport and the mechanisms of trauma and overuse that can occur. Understanding these injuries will increase the provider's breadth of knowledge and will bridge trust with patients who climb. PMID- 26359843 TI - Caring for Wrestlers. AB - Wrestling is a popular high school and college sport with an injury and illness rate second only to football. It is important that the physician providing medical care for wrestlers be familiar with the unique characteristics of wrestling and the associated common injuries and medical problems. Common orthopedic injuries include shoulder, elbow, and finger dislocation; prepatellar bursitis; knee medial collateral ligament sprains; and cervical strains. Skin infections are the most common cause of missed mat time for wrestlers. Physicians need to be able to identify and treat these infections, and know the rules regarding return to wrestling once an infection has been identified. Other conditions that are common include auricular hematomas, epistaxis, and brow lacerations. Physicians also need to be familiar with the medical issues involved with rapid weight loss and weight cycling, and understand the high school and college weight certification rules. PMID- 26359844 TI - Common Shoulder Injuries in American Football Athletes. AB - American football is a collision sport played by athletes at high speeds. Despite the padding and conditioning in these athletes, the shoulder is a vulnerable joint, and injuries to the shoulder girdle are common at all levels of competitive football. Some of the most common injuries in these athletes include anterior and posterior glenohumeral instability, acromioclavicular pathology (including separation, osteolysis, and osteoarthritis), rotator cuff pathology (including contusions, partial thickness, and full thickness tears), and pectoralis major and minor tears. In this article, we will review the epidemiology and clinical and radiographic workup of these injuries. We also will evaluate the effectiveness of surgical and nonsurgical management specifically related to high school, collegiate, and professional football athletes. PMID- 26359845 TI - The Expression and Cellular Localization of Galectin-1 and Galectin-3 in the Fallopian Tube Are Altered in Women with Tubal Ectopic Pregnancy. AB - Galectin-1 and galectin-3 are abundantly expressed at implantation sites in the uterus, suggesting their involvement in the establishment of pregnancy. In this study, we examined the expression and localization of galectin-1 and galectin-3 in fallopian tubes from nonpregnant women, and in those presenting with tubal ectopic pregnancy. There was no significant difference in the expression of either galectin-1 (LGALS1) or galectin-3 (LGALS3) transcripts in the fallopian tube across the menstrual cycle. Their expressions in the fallopian tube were inversely correlated to each other (r = -0.5134, p < 0.0001) and differentially localized. Galectin-1 protein was abundant in the stroma of nonpregnant fallopian tubes, whereas galectin-3 was mainly localized to the epithelium, notably to the cilia of ciliated cells and the apical cytoplasm of secretory cells. In ectopic pregnancies, LGALS3 expression was significantly reduced (p < 0.0001), but LGALS1 expression did not change when compared to nonpregnant fallopian tubes collected during the mid-secretory phase. The percentage of fallopian tube epithelial cells expressing galectin-3 in cilia tended to be reduced (p = 0.0685), with an accompanying loss of a normal ciliary structure, while nuclear galectin-3 increased (p < 0.05) in ectopic pregnancies. Epithelial immunostaining for galectin-1 tended to be elevated in fallopian tubes from women with ectopic pregnancy. Coculture of human trophoblast origin SW71 cells significantly increased LGALS1 expression in human fallopian tube epithelial OE-E6/E7 cells, suggesting that trophoblast-derived products regulate LGALS1 expression in the oviductal epithelium. These findings imply a differential contribution of galectin-1 and galectin-3 in the homeostasis of human fallopian tubes and in the pathophysiology of ectopic pregnancy. PMID- 26359846 TI - Facilitating Nurses' Engagement in Hospital Quality Improvement: The New Jersey Hospital Association's Implementation of Transforming Care at the Bedside. AB - Transforming Care at the Bedside (TCAB) is a program designed by the Robert Wood Johnson Foundation and the Institute for Healthcare Improvement to engage frontline staff in change processes to improve the work environment and patient care on nursing units. Originally designed and piloted in a small number of hospitals, TCAB is being disseminated through large-scale quality improvement (QI) collaboratives facilitated by professional organizations, such the New Jersey Hospital Association's Institute for Quality and Patient Safety (NJHA). This article presents the results of an evaluation of the NJHA dissemination effort. The evaluation team used an observational mixed-method evaluation design and multiple data sources to assess implementation of TCAB by nursing units in these facilities. The results show that most of the participating units successfully implemented the TCAB improvement processes. Nursing teamwork and three nursing-sensitive outcomes improved significantly over the course of TCAB, and TCAB unit managers attributed important improvements to their unit's participation. These findings suggest that TCAB is a viable mechanism for engaging frontline nursing staff in valuable QI activities. Other hospitals interested in furthering the culture and capacity for QI among frontline nursing unit staff should consider a TCAB collaborative for achieving these goals. PMID- 26359847 TI - Measurement of (233)U/(234)U ratios in contaminated groundwater using alpha spectrometry. AB - The uranium isotope (233)U is not usually observed in alpha spectra from environmental samples due to its low natural and fallout abundance. It may be present in samples from sites in the vicinity of nuclear operations such as reactors or fuel reprocessing facilities, radioactive waste disposal sites or sites affected by clandestine nuclear operations. On an alpha spectrum, the two most abundant alpha emissions of (233)U (4.784 MeV, 13.2%; and 4.824 MeV, 84.3%) will overlap with the (234)U doublet peak (4.722 MeV, 28.4%; and 4.775 MeV, 71.4%), if present, resulting in a combined (233+234)U multiplet. A technique for quantifying both (233)U and (234)U from alpha spectra was investigated. A series of groundwater samples were measured both by accelerator mass spectrometry (AMS) to determine (233)U/(234)U atom and activity ratios and by alpha spectrometry in order to establish a reliable (233)U estimation technique using alpha spectra. The GenieTM 2000 Alpha Analysis and Interactive Peak Fitting (IPF) software packages were used and it was found that IPF with identification of three peaks ((234)U minor, combined (234)U major and (233)U minor, and (233)U major) followed by interference correction on the combined peak and a weighted average activity calculation gave satisfactory agreement with the AMS data across the (233)U/(234)U activity ratio range (0.1-20) and (233)U activity range (2-300 mBq) investigated. Correlation between the AMS (233)U and alpha spectrometry (233)U was r(2) = 0.996 (n = 10). PMID- 26359848 TI - Long-term risk factors for substance-induced and primary psychosis after release from prison. A longitudinal study of substance users. AB - PURPOSE: The purpose of this study was to determine long-term risk factors for substance-induced and primary psychosis after release from prison. MATERIAL: We used a longitudinal register-based cohort study combining European version of Addiction Severity Index (Europ-ASI) interviews and the Swedish inpatient register. The study included 6217 individuals who were in the Swedish criminal justice system from 2001 to 2006. MEASUREMENTS: The outcomes were substance induced and primary psychosis as defined by the International Classification of Disease - 10th version. All variables for estimating baseline risk were drawn from the Europ-ASI interview, and included information on substance use, demographics and health. The interview database and the inpatient register were coupled, and groups were compared by using tests of significance and logistic regression. RESULTS: Polydrug use was the strongest predictor for substance induced psychosis (OR=9.55, 95% CI 3.42-26.67), but all substances imposed an increased risk. Previous psychiatric hospitalization and non-drug related hallucinations were significant, but weaker, risk factors. The only substance variable that predicted primary psychosis was cannabis (OR=2.62, 95% CI 1.39 4.96), but previous psychiatric hospitalization (OR=3.22, 95% CI 2.27-4.54) and non-drug related hallucinations (OR=4.00, 95% CI 2.82-5.67) were even stronger predictors. CONCLUSIONS: Cannabis use was a risk factor for primary psychosis, but other health related individual risk factors were even more important. Polydrug use was the strongest risk factor for substance-induced psychosis. PMID- 26359849 TI - Equine alpha-fetoprotein levels in Lipizzaner mares with normal pregnancies and with pregnancy loss. AB - Alpha-fetoprotein has proved to be a good indicator of fetal well-being in human medicine for decades. Although this molecule is present in most of the mammalian species including horses, reference values in healthy and high-risk pregnant mares have not yet been published. The aim of the present study was to determine whether equine alpha-fetoprotein (eqAFP) is a good indicator of complicated pregnancies in Lipizzaner mares. A total of 111 serum samples from 30 mares have been analyzed for eqAFP levels throughout gestation (Days 60-325). After the pregnancy was confirmed, 23 mares had normal pregnancies with viable foals, six had late embryonic loss, and one of the mares aborted in the ninth gestational month. Equine alpha-fetoprotein concentrations significantly differed in the normal group (72.93 +/- 49.25 pg/mL; mean +/- standard deviation) and in the complicated pregnancy loss group (152 +/- 36.48 pg/mL; mean +/- standard deviation). The mares' age, gestational age, and the conception rate significantly affected the alpha-fetoprotein concentrations in the normal group. Furthermore, notable individual differences occurred in eqAFP concentrations between mares. Equine alpha-fetoprotein seems to be an important indicator of fetal well-being in horses, but there are still some unanswered questions (levels in foals of different age, ponies, and draft horses) regarding this serum protein. Large-scale studies are needed to assess the specificity, sensitivity, and reliability of this test as a possible future diagnostic tool for fetal well being in horses. PMID- 26359850 TI - Characteristics of urethral and epididymal semen collected from domestic cats--A retrospective study of 214 cases. AB - This study was designed to describe and compare basic semen characteristics and sperm motility parameters obtained via computer-assisted sperm analysis (CASA) in feline semen collected from the urethra and epididymis, on the basis of large, unselected population of domestic cats. The semen collected from 214 males was subjected for routine semen assessment and CASA evaluation. Semen collected by urethral catheterization (CT) and by epididymal slicing (EP) has comparable characteristics according to total sperm count (47.7 +/- 42.1 and 52.9 +/- 45.0), subjective motility (71.1 +/- 17.0 and 69.3 +/- 13.9), viability (74.9 +/- 13.4 and 76.7 +/- 10.6), and morphology (52.6 +/- 19.0 and 47.2 +/- 17.4). The study of a large feline population confirmed a high incidence of teratospermy in cats, which negatively affects sperm motility parameters assessed by CASA. A lack of a correlation between CT and EP semen for total sperm count and viability, as well as occasional gross differences between the morphology of CT and EP semen of the same cat suggests that many factors may affect sperm cells, and the fertility and/or infertility of patients should not be assessed after examining only one sample. Additionally, technical problems with assessment of EP samples (understated results) suggest that CT semen is more appropriate for an analysis by CASA than EP. PMID- 26359851 TI - The importance of being genomic: Non-coding and coding sequences suggest different models of toxin multi-gene family evolution. AB - Studies of multi-gene protein families, including many toxins, are crucial for understanding the role of gene duplication in generating protein diversity in general. However, many evolutionary analyses of gene families are based on coding sequences, and do not take into account many potentially confounding evolutionary factors, such as recombination and convergence due to selection. We illustrate this using snake venom gene sequences from the Phospholipase A2 (PLA2) subfamily. Novel gene sequences from 20 species of understudied Asian pitvipers were analyzed alongside available genomic PLA2 sequences from another four crotaline and several viperine species. In contrast to previous analyses of this toxin family based on cDNA sequences, we find that duplication events are concentrated at the tips of the tree, suggesting that major functions such as presynaptic neurotoxicity have evolved convergently multiple times in pitvipers. We provide evidence that this discrepancy is due to differing evolutionary patterns between introns and exons. The effects of several well-known sources of bias on the phylogeny were small, compared to the effect of analyses based on different partitions of the gene (whole gene sequence, non-coding regions, cDNA sequence). Switches of function were found to be largely associated with strong selection, and with duplication events. Use of coding sequences for phylogeny estimation potentially produces incorrect inferences about the action of selection on individual lineages and sites. Our results have major implications for phylogenomic methods of functional inference as well as for our understanding of the evolution of multigene families. PMID- 26359853 TI - Subarachnoid hemorrhage secondary to ophthalmic artery avulsion. PMID- 26359852 TI - A new approach for investigating venom function applied to venom calreticulin in a parasitoid wasp. AB - A new method is developed to investigate functions of venom components, using venom gene RNA interference knockdown in the venomous animal coupled with RNA sequencing in the envenomated host animal. The vRNAi/eRNA-Seq approach is applied to the venom calreticulin component (v-crc) of the parasitoid wasp Nasonia vitripennis. Parasitoids are common, venomous animals that inject venom proteins into host insects, where they modulate physiology and metabolism to produce a better food resource for the parasitoid larvae. vRNAi/eRNA-Seq indicates that v crc acts to suppress expression of innate immune cell response, enhance expression of clotting genes in the host, and up-regulate cuticle genes. V-crc KD also results in an increased melanization reaction immediately following envenomation. We propose that v-crc inhibits innate immune response to parasitoid venom and reduces host bleeding during adult and larval parasitoid feeding. Experiments do not support the hypothesis that v-crc is required for the developmental arrest phenotype observed in envenomated hosts. We propose that an important role for some venom components is to reduce (modulate) the exaggerated effects of other venom components on target host gene expression, physiology, and survival, and term this venom mitigation. A model is developed that uses vRNAi/eRNA-Seq to quantify the contribution of individual venom components to total venom phenotypes, and to define different categories of mitigation by individual venoms on host gene expression. Mitigating functions likely contribute to the diversity of venom proteins in parasitoids and other venomous organisms. PMID- 26359854 TI - Thalamic atrophy predicts cognitive impairment in relapsing remitting multiple sclerosis. Effect on instrumental activities of daily living and employment status. AB - INTRODUCTION: Cognitive impairment is an important predictor of quality of life at all stages of MS. Magnetic Resonance Imaging (MRI) markers have been used to associate tissue damage with cognitive dysfunction. OBJECTIVE: The aim of the study was to designate the MRI marker that predicts cognitive decline and explore its effect on every day activities and employment status. METHODS: 50 RRMS patients and 31 healthy participants underwent neuropsychological assessment using the Trail Making Test (TMT) parts A and B, semantic and phonological verbal fluency task and a computerized cognitive screening battery (Central Nervous System Vital Signs). Everyday activities were evaluated with the instrumental activities of daily living (IADL) scale and employment status. Brain MRI was performed in all participants. We measured total lesion volume, third ventricle width, corpus callosum and thalamic atrophy. RESULTS: The frequency of cognitive dysfunction for our RRMS patients was 38%. RRMS patients differed significantly from controls on the TMTA, TMTB, phonological verbal fluency task, memory, psychomotor speed, reaction time and cognitive flexibility. Neuropsychological measures had a strong correlation with all MRI atrophy measures and a weak or moderate correlation with lesion volume. Psychomotor speed was the most sensitive marker for IADL, while memory and TMTB for employment status. Thalamic area was the most sensitive MRI marker for memory, psychomotor speed and TMTB.. CONCLUSION: Thalamic atrophy predicts the clinically meaningful cognitive decline in our RRMS patients. PMID- 26359855 TI - A novel RRM2B gene variant associated with Telbivudine-induced mitochondrial myopathy. PMID- 26359856 TI - Minimally invasive plate osteosynthesis in distal radius fractures with metaphyseal extension: A series of 13 cases. AB - To evaluate objective and subjective outcomes after minimally invasive volar locked plate fixation of distal radius fractures with metaphyseal extension, we retrospectively evaluated 13 patients with unstable distal radius fractures with metaphyseal extension, treated by minimally invasive volar locked plating. Patients' average age was 41 years. Two volar incisions, 2 to 3cm long, were made; indirect reduction was performed and a volar locked T-plate was placed submuscularly under fluoroscopy guidance. Twelve fractures healed after an average of 2.46 months; one patient needed revision due to a new injury. The plate had to be removed in one patient. On X-rays, radial height averaged 12.78mm, radial inclination averaged 21.34 degrees and volar tilt averaged 8.22 degrees . Flexion averaged 75 degrees , extension 71.5 degrees , pronation 82.08 degrees and supination 83.08 degrees . Grip strength averaged 83.75% of the contralateral wrist. The DASH score averaged 13.91 points and pain assessed on VAS averaged 0.92 points. In unstable distal radius fractures with metaphyseal extension, minimally invasive plate osteosynthesis using volar locked plates led to good reduction and stable fixation, with low pain levels, and good functional and esthetic results. Indirect reduction techniques, fluoroscopy, and restoration of radial length, rotation and alignment, are necessary to achieve these outcomes. LEVEL OF EVIDENCE: IV. PMID- 26359857 TI - Dellon's anterior submuscular transposition of the ulnar nerve: Retrospective study of 82 operated patients with 11.5 years' follow-up. AB - Anterior submuscular transposition of the ulnar nerve described by Dellon can solve the dynamic component of cubital tunnel syndrome at the elbow. We carried out a retrospective, single-surgeon study. The McGowan scale as modified by Goldberg (MG) was used preoperatively and at the final assessment; the QuickDASH was completed at the final assessment. The cohort comprised of 82 patients (38 females, 44 males) with a mean age of 61.2 years (37-92). The preoperative MG grade was: stage I (52%), IIA (28%), IIB (16%), III (4%). Three postoperative complications (3.5%) were recorded: two hematomas that did not require surgical revision and one case of elbow stiffness that resolved with physical therapy. Mean follow-up was 11.1 years (11-12). We identified 5 cases of confirmed recurrences (5.9%), 7 of secondary deterioration (8.5%) and 3 of initially poor result (3.5%). Sixty-six patients (86%) considered themselves cured at the final assessment. The MG scale at the last follow-up was: stage 0 (85.5%), I (9%), IIA (5%), III (0%). The QuickDASH was 11.88 (11-16). Mean time to recurrence was 6.3 years (1.5-10). Dellon's anterior submuscular transposition can be considered a reliable procedure. Eighty-six percent of patients were cured and 6% recurrence rate was noted. However, this is a demanding procedure. PMID- 26359858 TI - Proximal interphalangeal joint fractures treated with a dynamic external fixator: A multicenter and retrospective study of 88 cases. AB - Ligamentotaxis is now a well-established treatment method for proximal interphalangeal (PIP) joint fractures. Despite satisfactory results, the technique is considered complex and the devices cumbersome. The aim of this study was to evaluate a miniaturized dynamic external fixator (Ligamentotaxor((r))) for the management of these fractures. Eighty-six patients with 88 fractures of the PIP joint were treated at 10 European hand surgery centers. The device was applied within eight days of the injury and was removed 40-45 days after the injury. Treatment complications included superficial infection (4 cases), osteoarthritis (1 case), and localized but resolving complex regional pain syndrome (4 cases). The fracture healed in all cases. At final follow-up (mean: 15.2 months), average range of motion was 70 degrees (range: 0-110 degrees ). Functional results were comparable between the 10 participating centers. Pain occurred upon exertion in 47% of the patients, 40% were sensitive to weather changes and 26% experienced constant pain. The mean QuickDASH score was 15.7 (range: 11-37) and 83.7% of the patients had no limitations during their daily activities. The results of this series are similar to those reported in other studies of PIP fracture treatment with external fixators. This technique is reliable and reproducible. The device is easy to handle by surgeons and well tolerated by patients. We think that this simple, reliable technique could be relevant for the management of PIP joint fractures. PMID- 26359859 TI - CO2 Emissions from Direct Energy Use of Urban Households in India. AB - India hosts the world's second largest population and offers the world's largest potential for urbanization. India's urbanization trajectory will have crucial implications on its future GHG emission levels. Using household microdata from India's 60 largest cities, this study maps GHG emissions patterns and its determinants. It also ranks the cities with respect to their household actual and "counter-factual" GHG emissions from direct energy use. We find that household GHG emissions from direct energy use correlate strongly with income and household size; population density, basic urban services (municipal water, electricity, and modern cooking-fuels access) and cultural, religious, and social factors explain more detailed emission patterns. We find that the "greenest" cities (on the basis of household GHG emissions) are Bareilly and Allahabad, while the "dirtiest" cities are Chennai and Delhi; however, when we control for socioeconomic variables, the ranking changes drastically. In the control case, we find that smaller lower-income cities emit more than expected, and larger high-income cities emit less than expected in terms of counter-factual emissions. Emissions from India's cities are similar in magnitude to China's cities but typically much lower than those of comparable U.S. cities. Our results indicate that reducing urban heat-island effects and the associated cooling degree days by greening, switching to modern nonsolid cooking fuels, and anticipatory transport infrastructure investments are key policies for the low-carbon and inclusive development of Indian cities. PMID- 26359860 TI - PD-1, PD-L1 and PD-L2 Gene Expression on T-Cells and Natural Killer Cells Declines in Conjunction with a Reduction in PD-1 Protein during the Intensive Phase of Tuberculosis Treatment. AB - BACKGROUND: The PD-1 axis is a cell intrinsic immunoregulatory pathway that mediates T cell exhaustion in chronic infection particularly in some viral infections. We hypothesized that PD-1, PD-L1 and PD-L2 would be highly expressed in untreated tuberculosis patients compared to controls due to their chronic infection and would decrease with successful TB treatment. MATERIALS AND METHODS: Untreated tuberculosis patients (n = 26) were recruited at diagnosis and followed up during treatment. Household contacts (n = 24) were recruited to establish baseline differences. Blood gene expression ex vivo was investigated using qRT PCR. Flow cytometry was performed to establish protein expression patterns. RESULTS: PD-L1 gene expression was found to be elevated in active TB disease; however, this was not observed for PD-1 or PD-L2. The intensive phase of TB treatment was associated with a significant decline in PD-1, PD-L1 and PD-L2 gene expression. PD-1 protein expression on the surface of NK cells, CD8+ and CD4+ T cells was similar in patients with active TB disease compared to controls but declined with successful TB treatment, with the greatest decline occurring on the NK cells followed by CD8+ T cells and then CD4+ T cells. Granzyme B/PD-1 co expression declined with successful intensive phase treatment. CONCLUSION: Modulation of PD-1/PD-L1 pathway through TB treatment indicates changes in the peripheral T cell response caused by live Mycobacterium tuberculosis (Mtb) followed by the response to dead bacilli, antigen-release and immuno-pathology resolution. The PD-1 axis could be a host drug target for immunomodulatory treatments in the future. PMID- 26359861 TI - Adherence to Antihypertensive Therapy and Elevated Blood Pressure: Should We Consider the Use of Multiple Medications? AB - BACKGROUND: Although a majority of patients with hypertension require a multidrug therapy, this is rarely considered when measuring adherence from refill data. Moreover, investigating the association between refill non-adherence to antihypertensive therapy (AHT) and elevated blood pressure (BP) has been advocated. OBJECTIVE: Identify factors associated with non-adherence to AHT, considering the multidrug therapy, and investigate the association between non adherence to AHT and elevated BP. METHODS: A retrospective cohort study including patients with hypertension, identified from a random sample of 5025 Swedish adults. Two measures of adherence were estimated by the proportion of days covered method (PDC>=80%): (1) Adherence to any antihypertensive medication and, (2) adherence to the full AHT regimen. Multiple logistic regressions were performed to investigate the association between sociodemographic factors (age, sex, education, income), clinical factors (user profile, number of antihypertensive medications, healthcare use, cardiovascular comorbidities) and non-adherence. Moreover, the association between non-adherence (long-term and a month prior to BP measurement) and elevated BP was investigated. RESULTS: Non adherence to any antihypertensive medication was higher among persons < 65 years (Odds Ratio, OR 2.75 [95% CI, 1.18-6.43]) and with the lowest income (OR 2.05 [95% CI, 1.01-4.16]). Non-adherence to the full AHT regimen was higher among new users (OR 2.04 [95% CI, 1.32-3.15]), persons using specialized healthcare (OR 1.63, [95% CI, 1.14-2.32]), and having multiple antihypertensive medications (OR 1.85 [95% CI, 1.25-2.75] and OR 5.22 [95% CI, 3.48-7.83], for 2 and >=3 antihypertensive medications, respectively). Non-adherence to any antihypertensive medication a month prior to healthcare visit was associated with elevated BP. CONCLUSION: Sociodemographic factors were associated with non adherence to any antihypertensive medication while clinical factors with non adherence to the full AHT regimen. These differing findings support considering the use of multiple antihypertensive medications when measuring refill adherence. Monitoring patients' refill adherence prior to healthcare visit may facilitate interpreting elevated BP. PMID- 26359862 TI - Clinical Background of Patients with Sperm in Their Urinary Sediment. AB - INTRODUCTION: The detection rate and associated factors of at least one sperm in urinary sediment is not well-known in real clinical practice. AIMS: The aim of the present study was to evaluate the clinical features associated with the presence of sperm in urinary sediment in a large number of samples. METHODS: We conducted a cross-sectional study at Tokyo Saiseikai Central Hospital. We identified 5,005 males who were aged >=20 years in whom urinary sedimentation had been performed at least twice between May 2011 and June 2012. The sperm group included patients in whom at least one urinary sediment test performed under a microscope had detected at least one sperm. We evaluated the associations between the presence of at least one sperm in urinary sediment and clinical parameters such as various diseases and the use of particular oral medicines. MAIN OUTCOMES: In total, 1.6% (339/20,937) of urinary sediment samples contained at least one sperm. The sperm group consisted of 282 subjects (5.6%), and the no-sperm group included 4,723 subjects (94.3%). RESULTS: Multivariate analysis demonstrated that younger age (<65) (odds ratio [OR]: 1.71, 95% confidence interval [CI]: 1.32 2.21), the total number of examinations (>=4) (OR: 1.46, 95%CI: 1.11-1.92), diabetes (OR: 1.72, 95%CI: 1.31-2.25), a history of pelvic surgery for colon cancer (OR: 4.89, 95%CI: 2.38-10.02), alpha-1 blocker use (OR: 1.55, 95%CI: 1.16 2.08), a history of trans-urethral resection of the prostate (OR: 2.77, 95%CI: 1.46-5.13), and selective serotonin reuptake inhibitor use (OR: 2.12, 95%CI: 1.07 4.19) were independent predictors of the presence of at least one sperm in urinary sediment. CONCLUSION: There is considerable overlap between the factors associated with the presence of at least one sperm in urinary sediment and those that are strongly associated with ejaculatory disorders. PMID- 26359863 TI - Correction: Dawn and Dusk Set States of the Circadian Oscillator in Sprouting Barley (Hordeum vulgare) Seedlings. PMID- 26359864 TI - Host-Parasite Interactions in Chagas Disease: Genetically Unidentical Isolates of a Single Trypanosoma cruzi Strain Identified In Vitro via LSSP-PCR. AB - The present study aims at establishing whether the diversity in pathogenesis within a genetically diverse host population infected with a single polyclonal strain of Trypanosoma cruzi is due to selection of specific subpopulations within the strain. For this purpose we infected Swiss mice, a genetically diverse population, with the polyclonal strain of Trypanosoma cruzi Berenice-78 and characterized via LSSP-PCR the kinetoplast DNA of subpopulations isolated from blood samples collected from the animals at various times after inoculation (3, 6 and 12 months after inoculation). We examined the biological behavior of the isolates in acellular medium and in vitro profiles of infectivity in Vero cell medium. We compared the characteristics of the isolates with the inoculating strain and with another strain, Berenice 62, isolated from the same patient 16 years earlier. We found that one of the isolates had intermediate behavior in comparison with Berenice-78 and Berenice-62 and a significantly different genetic profile by LSSP-PCR in comparison with the inoculating strain. We hereby demonstrate that genetically distinct Trypanosoma cruzi isolates may be obtained upon experimental murine infection with a single polyclonal Trypanosoma cruzi strain. PMID- 26359865 TI - Evaluation of TNF-alpha, IL-10 and IL-6 Cytokine Production and Their Correlation with Genotype Variants amongst Tuberculosis Patients and Their Household Contacts. AB - BACKGROUND: Household contacts of diagnostically established tuberculosis (TB) patients are highly susceptible to disease development. It is surmised that cytokines perhaps play a synergistic and a prognostic role in the activation of the otherwise latent infection in these house hold contacts. Evaluation of the cytokines and any of their inherent polymorphisms might provide a useful diagnostic tool in evaluating the immune regulation and the progression of the disease. The cytokines thus released in a paracrine manner in serum may also provide an indirect measure of the cytokine function. OBJECTIVE: The present study was aimed to evaluate the levels of TNF-alpha, IL-10 & IL-6 cytokines and their correlation with genotype variants amongst tuberculosis patients and their household contacts. METHODS: The cytokine levels were estimated in serum by enzyme-linked immunosorbent assay (ELISA) and their polymorphisms were studied by amplification refractory mutation system polymerase chain reaction (ARMs PCR) in active pulmonary tuberculosis patients (APTB = 150), household contacts (HHC = 190), and healthy controls (HC = 150). RESULTS: The median values of TNF-alpha cytokine were significantly high among APTB and HHC compared to HCs (P< 0.0001 and 0.0001). IL-6 levels also were elevated among APTB compared to HHC and HC, and a significant difference was observed between APTB and HHC at P<0.0001; APTB & HC at P< 0.04; HHC & HC at P< 0.01. The IL-10 levels were low in APTB compared to HHC and HCs and no significant difference was observed. TNF-alpha/IL-10 ratio was significant and indicated Th1 predominance in APTB and HHC. IL-6/IL-10 showed pronounced Th1 expression in APTB and Th2 in HHC and HC. The ROC analysis indicated that both IL-10 and IL-6 can be used to decide the risk of exposed individual to a disease. The results of multivariate analysis indicate that IL-10 (-1082) GA genotype was significantly associated with p<0.028 in APTB. No significant association was observed between genotypes, other serum cytokine levels and clinical characteristics between APTB, HHC and HCs. CONCLUSION: Large sample size with follow-up at different time points may further illuminate the role of IL-10 and IL-6 cytokines as a prognostic marker in house hold contacts. PMID- 26359866 TI - Heads First: Visual Aftereffects Reveal Hierarchical Integration of Cues to Social Attention. AB - Determining where another person is attending is an important skill for social interaction that relies on various visual cues, including the turning direction of the head and body. This study reports a novel high-level visual aftereffect that addresses the important question of how these sources of information are combined in gauging social attention. We show that adapting to images of heads turned 25 degrees to the right or left produces a perceptual bias in judging the turning direction of subsequently presented bodies. In contrast, little to no change in the judgment of head orientation occurs after adapting to extremely oriented bodies. The unidirectional nature of the aftereffect suggests that cues from the human body signaling social attention are combined in a hierarchical fashion and is consistent with evidence from single-cell recording studies in nonhuman primates showing that information about head orientation can override information about body posture when both are visible. PMID- 26359867 TI - The WOPR Domain Protein OsaA Orchestrates Development in Aspergillus nidulans. AB - Orchestration of cellular growth and development occurs during the life cycle of Aspergillus nidulans. A multi-copy genetic screen intended to unveil novel regulators of development identified the AN6578 locus predicted to encode a protein with the WOPR domain, which is a broadly present fungi-specific DNA binding motif. Multi-copy of AN6578 disrupted the normal life cycle of the fungus leading to enhanced proliferation of vegetative cells, whereas the deletion resulted in hyper-active sexual fruiting with reduced asexual development (conidiation), thus named as osaA (Orchestrator of Sex and Asex). Further genetic studies indicate that OsaA balances development mainly by repressing sexual development downstream of the velvet regulator VeA. The absence of osaA is sufficient to suppress the veA1 allele leading to the sporulation levels comparable to veA+ wild type (WT). Genome-wide transcriptomic analyses of WT, veA1, and DeltaosaA veA1 strains by RNA-Seq further corroborate that OsaA functions in repressing sexual development downstream of VeA. However, OsaA also plays additional roles in controlling development, as the DeltaosaA veA1 mutant exhibits precocious and enhanced formation of Hulle cells compared to WT. The OsaA orthologue of Aspergillus flavus is able to complement the osaA null phenotype in A. nidulans, suggesting a conserved role of this group of WOPR domain proteins. In summary, OsaA is an upstream orchestrator of morphological and chemical development in Aspergillus that functions downstream of VeA. PMID- 26359868 TI - Low-Concentration Arsenic Trioxide Inhibits Skeletal Myoblast Cell Proliferation via a Reactive Oxygen Species-Independent Pathway. AB - Myoblast proliferation and differentiation are essential for skeletal muscle regeneration. Myoblast proliferation is a critical step in the growth and maintenance of skeletal muscle. The precise action of inorganic arsenic on myoblast growth has not been investigated. Here, we investigated the in vitro effect of inorganic arsenic trioxide (As2O3) on the growth of C2C12 myoblasts. As2O3 decreased myoblast growth at submicromolar concentrations (0.25-1 MUM) after 72 h of treatment. Submicromolar concentrations of As2O3 did not induce the myoblast apoptosis. Low-concentration As2O3 (0.5 and 1 MUM) significantly suppressed the myoblast cell proliferative activity, which was accompanied by a small proportion of bromodeoxyuridine (BrdU) incorporation and decreased proliferating cell nuclear antigen (PCNA) protein expression. As2O3 (0.5 and 1 MUM) increased the intracellular arsenic content but did not affect the reactive oxygen species (ROS) levels in the myoblasts. Cell cycle analysis indicated that low-concentrations of As2O3 inhibited cell proliferation via cell cycle arrest in the G1 and G2/M phases. As2O3 also decreased the protein expressions of cyclin D1, cyclin E, cyclin B1, cyclin-dependent kinase (CDK) 2, and CDK4, but did not affect the protein expressions of p21 and p27. Furthermore, As2O3 inhibited the phosphorylation of Akt. Insulin-like growth factor-1 significantly reversed the inhibitory effect of As2O3 on Akt phosphorylation and cell proliferation in the myoblasts. These results suggest that submicromolar concentrations of As2O3 alter cell cycle progression and reduce myoblast proliferation, at least in part, through a ROS-independent Akt inhibition pathway. PMID- 26359869 TI - Digenic Inheritance in Cystinuria Mouse Model. AB - Cystinuria is an aminoaciduria caused by mutations in the genes that encode the two subunits of the amino acid transport system b0,+, responsible for the renal reabsorption of cystine and dibasic amino acids. The clinical symptoms of cystinuria relate to nephrolithiasis, due to the precipitation of cystine in urine. Mutations in SLC3A1, which codes for the heavy subunit rBAT, cause cystinuria type A, whereas mutations in SLC7A9, which encodes the light subunit b0,+AT, cause cystinuria type B. By crossing Slc3a1-/- with Slc7a9-/- mice we generated a type AB cystinuria mouse model to test digenic inheritance of cystinuria. The 9 genotypes obtained have been analyzed at early (2- and 5 months) and late stage (8-months) of the disease. Monitoring the lithiasic phenotype by X-ray, urine amino acid content analysis and protein expression studies have shown that double heterozygous mice (Slc7a9+/-Slc3a1+/-) present lower expression of system b0,+ and higher hyperexcretion of cystine than single heterozygotes (Slc7a9+/-Slc3a1+/+ and Slc7a9+/+Slc3a1+/-) and give rise to lithiasis in 4% of the mice, demonstrating that cystinuria has a digenic inheritance in this mouse model. Moreover in this study it has been demonstrated a genotype/phenotype correlation in type AB cystinuria mouse model providing new insights for further molecular and genetic studies of cystinuria patients. PMID- 26359870 TI - Adverse effects of irreversible electroporation of malignant liver tumors under CT fluoroscopic guidance: a single-center experience. AB - PURPOSE: We aimed to describe the frequency of adverse events after computed tomography (CT) fluoroscopy-guided irreversible electroporation (IRE) of malignant hepatic tumors and their risk factors. METHODS: We retrospectively analyzed 85 IRE ablation procedures of 114 malignant liver tumors (52 primary and 62 secondary) not suitable for resection or thermal ablation in 56 patients (42 men and 14 women; median age, 61 years) with regard to mortality and treatment related complications. Complications were evaluated according to the standardized grading system of the Society of Interventional Radiology. Factors influencing the occurrence of major and minor complications were investigated. RESULTS: No IRE-related death occurred. Major complications occurred in 7.1% of IRE procedures (6/85), while minor complications occurred in 18.8% (16/85). The most frequent major complication was postablative abscess (4.7%, 4/85) which affected patients with bilioenteric anastomosis significantly more often than patients without this condition (43% vs. 1.3%, P = 0.010). Bilioenteric anastomosis was additionally identified as a risk factor for major complications in general (P = 0.002). Minor complications mainly consisted of hemorrhage and portal vein branch thrombosis. CONCLUSION: The current study suggests that CT fluoroscopy-guided IRE ablation of malignant liver tumors may be a relatively low-risk procedure. However, patients with bilioenteric anastomosis seem to have an increased risk of postablative abscess formation. PMID- 26359871 TI - Impact of radiation dose and iterative reconstruction on pulmonary nodule measurements at chest CT: a phantom study. AB - PURPOSE: We aimed to identify the impact of radiation dose and iterative reconstruction (IR) on measurement of pulmonary nodules by chest computed tomography (CT). METHODS: CT scans were performed on a chest phantom containing various nodules (diameters of 3, 5, 8, 10, and 12 mm; +100, -630 and -800 HU for each diameter) at 80, 100, 120 kVp and 10, 20, 50, 100 mAs (a total of 12 radiation dose settings). Each CT was reconstructed using filtered back projection, iDose4, and iterative model reconstruction (IMR). Thereafter, two radiologists measured the diameter and attenuation of the nodules. Noise, contrast-to-noise ratio and signal-to-noise ratio of CT images were also obtained. Influence of radiation dose and reconstruction algorithm on measurement error and objective image quality metrics was analyzed using generalized estimating equations. RESULTS: The 80 kVp, 10 mAs CT scan was not feasible for the measurement of 3 mm sized simulated ground-glass nodule (GGN); otherwise, diameter measurement error was not significantly influenced by radiation dose (P > 0.05). IR did not have a significant impact on diameter measurement error for simulated solid nodules (P > 0.05). However, for simulated GGNs, IMR was associated with significantly decreased relative diameter measurement error (P < 0.001). Attenuation measurement error was not significantly influenced by either radiation dose or reconstruction algorithm (P > 0.05). Objective image quality was significantly better with IMR (P < 0.05). CONCLUSION: Nodule measurements were not affected by radiation dose except for 3 mm simulated GGN on 80 kVp, 10 mAs dose setting. However, for GGNs, IMR may help reduce diameter measurement error while improving image quality. PMID- 26359873 TI - Imaging findings and endovascular management of iatrogenic hepatic arterial injuries. AB - Iatrogenic hepatic arterial injuries (IHAIs) include pseudoaneurysm, extravasation, arteriovenous fistula, arteriobiliary fistula, and dissection. IHAIs are usually demonstrated following percutaneous transhepatic biliary drainage, percutaneous liver biopsy, liver surgery, chemoembolization, radioembolization, and endoscopic retrograde cholangiopancreatography. The latency period between the intervention and diagnosis varies. The most common symptom is hemorrhage, and the most common lesion is pseudoaneurysm. Computed tomography angiography (CTA) is mostly performed prior to angiography, and IHAIs are demonstrated on CTA in most of the patients. Patients with IHAI are mostly treated by coils, but some patients may be treated by liquid embolic materials or stent-grafts. CTA can also be used in the follow-up period. Endovascular treatment is a safe and minimally invasive treatment option with high success rates. PMID- 26359872 TI - CT findings in acute peritonitis: a pattern-based approach. AB - Many inflammatory and infectious entities may acutely affect the peritoneum causing a thickening of its layers. Unfortunately, several acute peritoneal diseases can have overlapping features, both clinically and at imaging. Therefore, the awareness of the clinical context, although useful, may be sometimes insufficient to identify the underlying cause. This article provides a specific computed tomography-based approach including morphologic characteristics of peritoneal thickening (e.g., smooth, irregular, or nodular) and ancillary findings to narrow the differential diagnosis of acute peritonitis. PMID- 26359874 TI - Split-bolus MR urography: synchronous visualization of obstructing vessels and collecting system in children. AB - Several vascular abnormalities related with urinary system such as crossing accessory renal vessels, retroiliac ureters, retrocaval ureters, posterior nutcracker syndrome, and ovarian vein syndrome may be responsible for urinary collecting system obstruction. Split-bolus magnetic resonance urography (MRU) using contrast material as two separate bolus injections provides superior demonstration of the collecting system and obstructing vascular anomalies simultaneously and enables accurate preoperative radiologic diagnosis. In this pictorial review we aimed to outline the split-bolus MRU technique in children, list the coexisting congenital collecting system and vascular abnormalities, and exhibit the split-bolus MRU appearances of concurrent urinary collecting system and vascular abnormalities. PMID- 26359875 TI - Single-stage endovascular treatment in patients with severe extracranial large vessel stenosis and concomitant ipsilateral unruptured intracranial aneurysm. AB - PURPOSE: We aimed to evaluate the safety and effectiveness of single-stage endovascular treatment in patients with severe extracranial large vessel stenosis and concomitant ipsilateral unruptured intracranial aneurysm. METHODS: Hospital database was screened for patients who underwent single-stage endovascular treatment between February 2008 and June 2013 and seven patients were identified. The procedures included unilateral carotid artery stenting (CAS) (n=4), bilateral CAS (n=2), and proximal left subclavian artery stenting (n=1) along with ipsilateral intracranial aneurysm treatment (n=7). The mean internal carotid artery stenosis was 81.6% (range, 70%-95%), and the subclavian artery stenosis was 90%. All aneurysms were unruptured. The mean aneurysm diameter was 7.7 mm (range, 5-13 mm). The aneurysms were ipsilateral to the internal carotid artery stenosis (internal carotid artery aneurysm) in five patients, and in the anterior communicating artery in one patient. The patient with subclavian artery stenosis had a fenestration aneurysm in the proximal basilar artery. Stenting of the extracranial large vessel stenosis was performed before aneurysm treatment in all patients. In two patients who underwent bilateral CAS, the contralateral carotid artery stenosis, which had no aneurysm distally, was treated initially. RESULTS: There were no procedure-related complications or technical failure. The mean clinical follow-up period was 18 months (range, 9-34 months). One patient who underwent unilateral CAS experienced contralateral transient ischemic attack during the clinical follow-up. There was no restenosis on six-month follow-up angiograms, and all aneurysms were adequately occluded. CONCLUSION: A single stage procedure appears to be feasible for treatment of patients with severe extracranial large vessel stenosis and concomitant ipsilateral intracranial aneurysm. PMID- 26359876 TI - Monitorization of chemotherapy response using diffusion-weighted imaging in neuroblastoma. PMID- 26359877 TI - Volumetric thin-section CT: evaluation of pulmonaryinterlobar fissures. AB - PURPOSE: We aimed to perform an imaging analysis of interlobar fissures and their variations using thin-section computed tomography (CT). METHODS: Volumetric thin section CT scanning was performed in 208 subjects. Interlobar fissures were observed on axial images, and reconstructed coronal and sagittal images were observed by multiplanar reformatting (MPR). The vessel distributions were verified by maximal intensity projection (MIP). On the axial images, the interlobar fissures were characterized by lines of hyperattenuation, bands of hyperattenuation, avascular zones, and mixed imaging. The interlobar fissures were divided into seven grades according to the percentage of defects over the entire fissure. RESULTS: On the axial images, of all interlobar fissures without avascular zones, 70.2% of the right oblique fissures (ROFs) and 94.2% of the left oblique fissures (LOFs) appeared as lines, and 83.2% of the horizontal fissures (HFs) appeared as bands. All of the interlobar fissures appeared as lines on the coronal and sagittal images. Of all cases, 17.8% showed fully complete interlobar fissures for all three fissures. Incomplete fissures included 41.3% of ROFs, 58.2% of HFs, and 45.2% of LOFs. In ROFs and LOFs, discontinuity was most frequently below 20%, while in HFs discontinuity was most frequently 41%-60%. The most common classification of incomplete interlobar fissures was a discontinuous avascular zone. CONCLUSION: Incomplete interlobar fissures are common variations of interlobar fissures. Techniques including volumetric thin-section CT, MPR, and MIP can assist in the diagnosis of incomplete interlobar fissures. PMID- 26359878 TI - Cross-sectional area measurement of the coronary arteries using CT angiography at the level of the bifurcation: is there a relationship? AB - PURPOSE: Our aim was to determine whether there is a correlation between cross sectional areas of the left main coronary artery (LMCA), left anterior descending artery (LAD), and circumflex artery (CX) in normal cases using coronary CT angiography. METHOD: Examinations of 180 patients (119 men and 61 women) were selected among 2248 consecutive coronary CT angiography studies. Cross-sectional areas of LMCA, LAD, and CX were measured at the level of bifurcation. Correlation between age, height, and body mass index and coronary artery cross-sectional areas was investigated and possibility of formulating a correlation between the cross-sectional areas of LMCA, LAD, and CX was explored. RESULTS: Mean cross sectional areas of LMCA, LAD, and CX were found as 17.4+/-3.9 mm2, 12.5+/-3.1 mm2, and 10.5+/-3.0 mm2, respectively. While cross-sectional areas of LMCA and LAD were significantly larger in men, no significant difference was found between the sectional areas of CX in men and women. A multiple regression analysis was conducted to elucidate the relationship between the cross-sectional areas of LMCA LAD, and CX. Our analysis showed that the relationship between LMCA, LAD, and CX cross-sectional areas can be formulated as follows: LMCA=3.870 + 0.718*LAD + 0.434*CX. CONCLUSION: There is a correlation between the cross-sectional areas of LMCA, LAD, and CX at the level of bifurcation, and this correlation can be expressed with a formula. PMID- 26359879 TI - Geometrical characteristics after Y-stenting of the basilar bifurcation. AB - PURPOSE: We aimed to investigate the angular changes after Y-stenting of the basilar bifurcation aneurysms. METHODS: A total of 19 patients (age range, 27-80 years; mean age, 52.5 years) underwent Y-stent coiling for basilar bifurcation aneurysm. Three vascular angles (alpha, beta1, beta2) were measured in the anteroposterior plane. beta1 and beta2 represented the angles between the basilar artery and the proximal P1 segments of the right and left posterior cerebral arteries, respectively. alpha represented the complementary angle between the beta1 and beta2 angles. Angles were measured before and after stent deployment. Diameters of the basilar artery and P2 segment of the posterior cerebral artery were measured at both sides. Correlation between vascular diameter and angular change of the basilar bifurcation was investigated. RESULTS: Statistically significant alpha, beta1, and beta2 angle changes were found after stent deployment (P < 0.001). There was no statistically significant relationship between the diameter of the basilar artery and the alpha, beta1, beta2 angle changes (P > 0.05). There was no statistically significant relationship between the diameter of the posterior cerebral artery and the beta angle change (P > 0.05). We found a statistically significant inverse correlation between pre-stent beta angle and post-stent angle change (right side, P = 0.008; left side, P < 0.001). CONCLUSION: Y-stenting narrows the effective neck and straightens the vascular bifurcation angle. Most of the angular remodeling occurs on the side that had a more acute angle before stent deployment. PMID- 26359880 TI - The role of ultrasonographic findings to predict molecular subtype, histologic grade, and hormone receptor status of breast cancer. AB - PURPOSE: The correlation between imaging findings and pathologic characteristics of tumors may provide information for diagnosis and treatment of cancer. The aim of this study is to determine whether ultrasound features of breast cancer are associated with molecular subtype, histologic grade, and hormone receptor status, as well as assess the predictive value of these features. METHODS: A total of 201 consecutive invasive breast cancer patients were reviewed from the database according to the Breast Imaging and Reporting Data System (BI-RADS). Tumor margins were classified as circumscribed and noncircumscribed. Noncircumscribed group was divided into indistinct, spiculated, angular, and microlobulated. The posterior acoustic features were divided into four categories: shadowing, enhancement, no change, and mixed pattern. RESULTS: Tumors with posterior shadowing were more likely to be of nontriple negative subtype (odds ratio [OR], 7.42; 95% CI, 2.10-24.99; P = 0.002), low histologic grade (grade 1 or 2 vs. grade 3: OR, 2.42; 95% CI, 1.34-4.35; P = 0.003) and having at least one positive receptor (OR, 3.36; 95% CI, 1.55-7.26; P = 0.002). Tumors with circumscribed margins were more often triple-negative subtype (OR, 6.72; 95% CI, 2.56-17.65; P < 0.001), high grade (grade 3 vs. grade 1 or 2: OR, 5.42; 95% CI, 2.66-11.00; P < 0.001) and hormone receptor negative (OR, 4.87; 95% CI, 2.37-9.99; P < 0.001). CONCLUSION: Sonographic features are strongly associated with molecular subtype, histologic grade, and hormone receptor status of the tumor. These findings may separate triple-negative breast cancer from other molecular subtypes. PMID- 26359882 TI - Mind and antibody: the return of immunopsychiatry. PMID- 26359881 TI - Comparison of Outcomes of Hematopoietic Cell Transplants from T-Replete Haploidentical Donors Using Post-Transplantation Cyclophosphamide with 10 of 10 HLA-A, -B, -C, -DRB1, and -DQB1 Allele-Matched Unrelated Donors and HLA-Identical Sibling Donors: A Multivariable Analysis Including Disease Risk Index. AB - Outcomes of 475 consecutive patients undergoing first allogeneic transplantation for hematologic malignancy performed using T-replete HLA-haploidentical donors and post-transplantation cyclophosphamide (HIDT; n = 116) were compared with contemporaneous patients transplanted from 10 of 10 HLA allele-matched unrelated donors (MUDT; n = 178) or HLA-identical sibling donors (MRDT; n = 181). Uniform supportive care measures and assessments were used. Median follow-up was 45 months. HIDT patients were more likely than MUDT patients to be black (44% versus 2%; P < .001). At 2 years after transplantation, estimates of overall survival were 57% for HIDT, 59% for MUDT, and 72% for MRDT (P not significant [NS] for HIDT versus MUDT; P = .02 for HIDT versus MRDT); corresponding disease-free survival rates were 54%, 50%, and 56% (P NS for both comparisons). The respective cumulative incidences (CIs) of nonrelapse mortality were 17%, 16%, 14%, and those of relapse were 29%, 34%, and 30% (P NS for all). The respective CIs of acute graft-versus-host disease (GVHD) grade II-IV were 41%, 48%, and 28% (P = NS for HIDT versus MUDT; P = .005 for HIDT versus MRDT). At 2 years, the respective CIs of moderate/severe chronic GVHD were 31%, 47%, and 44% (P = .004 for HIDT versus MUDT; P = .032 for HIDT versus MRDT) and 19% of HIDT recipients, 42% of MUDT recipients, and 35% of MRDT recipients were on systemic immunosuppressive treatment (P = .007 for HIDT versus MUDT). In recipients of peripheral blood stem cell grafts, the incidence of moderate-severe chronic GVHD was significantly lower in HIDT recipients compared with MUDT recipients (2-year CI, 25% versus 48%; P = .002). In a multivariate analysis incorporating Disease Risk Index and other significant covariates, survival (hazard ratio [HR], 1.31; P = .15) and disease-free survival (HR, 0.96; P = .79) were not significantly different between HIDT and MUDT recipients, but the incidence of chronic GVHD was lower in HIDT recipients (moderate-severe, HR, 0.59; P = .007). HIDT produced similar long term survival with lower rates of chronic GVHD than optimally matched MUDT. HIDT should be considered a standard of care option for patients lacking a matched sibling donor. PMID- 26359883 TI - Online CBT in patients with multiple sclerosis and depression. PMID- 26359884 TI - The relationship between depression and violent crime. PMID- 26359885 TI - Potent questions about cannabis and mental health. PMID- 26359886 TI - Suicide, unemployment, and the effect of economic recession. PMID- 26359887 TI - Psychoneuroimmunology or immunopsychiatry? PMID- 26359888 TI - Asia-pacific ready to act on mental health target in the SDGs. PMID- 26359889 TI - Personality disorder and population mental health. PMID- 26359890 TI - Agony, misery, woe: a new role for media advice columns. PMID- 26359892 TI - Corrections. PMID- 26359894 TI - Hearing Voices: tracing the borders of normality. PMID- 26359895 TI - Colin Drummond. PMID- 26359896 TI - Life and luxury in Monks Orchard: from Bethlem Hotel to community care, 1930 2000. PMID- 26359898 TI - Wrestling with the truth. PMID- 26359897 TI - BDSM: psychotherapy's grey area. PMID- 26359899 TI - A bird, a plane, Superman? PMID- 26359900 TI - An online programme to reduce depression in patients with multiple sclerosis: a randomised controlled trial. AB - BACKGROUND: With a lifetime risk for major depressive disorder of up to 50%, depression is a common comorbidity in multiple sclerosis but remains widely underdiagnosed and untreated. We investigated the potential of a fully automated, internet-based, cognitive behavioural therapy programme, Deprexis, to reduce depressive symptoms in patients with multiple sclerosis. METHODS: For this randomised controlled trial, we recruited patients from an outpatient clinic in Hamburg, Germany. Patients aged 18-65 years were eligible for inclusion if they had multiple sclerosis and self-reported depressive symptoms. By use of a computer-generated randomisation sequence, we allocated 90 patients (1:1; no blocking or stratification) to either the intervention group or a waitlist control group for 9 weeks. The primary endpoint was the Beck Depression Inventory (BDI), as assessed by an intention-to-treat analysis. This trial is registered with ClinicalTrials.gov, number NCT01663649. FINDINGS: 71 patients completed the trial: 35 patients in the intervention group and 36 patients in the control group. During the intervention, BDI scores decreased in the Deprexis group and increased in the control group, yielding a positive effect of Deprexis relative to the waitlist group (mean group difference -4.02 points [95% CI -7.26 to 0.79], p=0.015, effect size d=0.53). Worsening of depressive symptoms from below to above the clinical cutoff (BDI >13) occurred in three (7%) of 45 patients in the control group and no patients in the Deprexis group. We noted no adverse events with respect to new occurrence of suicidal ideation during the trial. INTERPRETATION: Psychological online-intervention programmes could be suitable for patients with multiple sclerosis who are unable to regularly attend therapeutic sessions because of mobility impairments. FUNDING: European Union and the Deutsche Forschungsgemeinschaft. PMID- 26359901 TI - Proportion of patients in south London with first-episode psychosis attributable to use of high potency cannabis: a case-control study. AB - BACKGROUND: The risk of individuals having adverse effects from drug use (eg, alcohol) generally depends on the frequency of use and potency of the drug used. We aimed to investigate how frequent use of skunk-like (high-potency) cannabis in south London affected the association between cannabis and psychotic disorders. METHODS: We applied adjusted logistic regression models to data from patients aged 18-65 years presenting to South London and Maudsley NHS Foundation Trust with first-episode psychosis and population controls recruited from the same area of south London (UK) to estimate the effect of the frequency of use, and type of cannabis used on the risk of psychotic disorders. We then calculated the proportion of new cases of psychosis attributable to different types of cannabis use in south London. FINDINGS: Between May 1, 2005, and May 31, 2011, we obtained data from 410 patients with first-episode psychosis and 370 population controls. The risk of individuals having a psychotic disorder showed a roughly three-times increase in users of skunk-like cannabis compared with those who never used cannabis (adjusted odds ratio [OR] 2.92, 95% CI 1.52-3.45, p=0.001). Use of skunk like cannabis every day conferred the highest risk of psychotic disorders compared with no use of cannabis (adjusted OR 5.4, 95% CI 2.81-11.31, p=0.002). The population attributable fraction of first-episode psychosis for skunk use for our geographical area was 24% (95% CI 17-31), possibly because of the high prevalence of use of high-potency cannabis (218 [53%] of 410 patients) in our study. INTERPRETATION: The ready availability of high potency cannabis in south London might have resulted in a greater proportion of first onset psychosis cases being attributed to cannabis use than in previous studies. FUNDING: UK National Institute of Health Research (NIHR) Specialist Biomedical Research Centre for Mental Health, SLaM and the Institute of Psychiatry at King's College London, Psychiatry Research Trust, Maudsley Charity Research Fund, and th European Community's Seventh Framework Program grant (agreement No. HEALTH-F2-2009-241909 [Project EU-GEI]). PMID- 26359902 TI - Modelling suicide and unemployment: a longitudinal analysis covering 63 countries, 2000-11. AB - BACKGROUND: As with previous economic downturns, there has been debate about an association between the 2008 economic crisis, rising unemployment, and suicide. Unemployment directly affects individuals' health and, unsurprisingly, studies have proposed an association between unemployment and suicide. However, a statistical model examining the relationship between unemployment and suicide by considering specific time trends among age-sex-country subgroups over wider world regions is still lacking. We aimed to enhance knowledge of the specific effect of unemployment on suicide by analysing global public data classified according to world regions. METHODS: We retrospectively analysed public data for suicide, population, and economy from the WHO mortality database and the International Monetary Fund's world economic outlook database from 2000 to 2011. We selected 63 countries based on sample size and completeness of the respective data and extracted the information about four age groups and sex. To check stability of findings, we conducted an overall random coefficient model including all study countries and four additional models, each covering a different world region. FINDINGS: Despite differences in the four world regions, the overall model, adjusted for the unemployment rate, showed that the annual relative risk of suicide decreased by 1.1% (95% CI 0.8-1.4) per year between 2000 and 2011. The best and most stable final model indicated that a higher suicide rate preceded a rise in unemployment (lagged by 6 months) and that the effect was non-linear with higher effects for lower baseline unemployment rates. In all world regions, the relative risk of suicide associated with unemployment was elevated by about 20 30% during the study period. Overall, 41,148 (95% CI 39,552-42,744) suicides were associated with unemployment in 2007 and 46,131 (44,292-47,970) in 2009, indicating 4983 excess suicides since the economic crisis in 2008. INTERPRETATION: Suicides associated with unemployment totalled a nine-fold higher number of deaths than excess suicides attributed to the most recent economic crisis. Prevention strategies focused on the unemployed and on employment and its conditions are necessary not only in difficult times but also in times of stable economy. FUNDING: University of Zurich. PMID- 26359905 TI - Health services, suicide, and self-harm: patient distress and system anxiety. AB - Patients often become distressed in health settings, and provision of emotional support is a routine part of clinical care. However, in some situations, patient distress can become disturbing to both clinicians and patients, and can affect ordinary therapeutic engagement. We argue that health systems that support people presenting with suicidal acts and self-harm are particularly at risk of providing maladaptive responses, which we have termed dysregulation. If health systems become dysregulated, staff and patients might find it difficult to think clearly and respond adaptively. We describe some common characteristics of dysregulation, including negative feelings about patients, an inappropriately narrow focus on diagnosis and risk assessment, and ad-hoc, abrupt, and inconsistent decision making. These dysregulated responses might impair more adaptive responses such as containment of distress, safety planning, and negotiated responsibility with patients and carers. We discuss the main drivers of dysregulation and the implications for clinical practice in the management of self-harm and suicide risk. PMID- 26359906 TI - Lessons from the creation of Canada's poorest postal code. PMID- 26359904 TI - Nutritional medicine as mainstream in psychiatry. AB - Psychiatry is at an important juncture, with the current pharmacologically focused model having achieved modest benefits in addressing the burden of poor mental health worldwide. Although the determinants of mental health are complex, the emerging and compelling evidence for nutrition as a crucial factor in the high prevalence and incidence of mental disorders suggests that diet is as important to psychiatry as it is to cardiology, endocrinology, and gastroenterology. Evidence is steadily growing for the relation between dietary quality (and potential nutritional deficiencies) and mental health, and for the select use of nutrient-based supplements to address deficiencies, or as monotherapies or augmentation therapies. We present a viewpoint from an international collaboration of academics (members of the International Society for Nutritional Psychiatry Research), in which we provide a context and overview of the current evidence in this emerging field of research, and discuss the future direction. We advocate recognition of diet and nutrition as central determinants of both physical and mental health. PMID- 26359907 TI - Self-assembly of diphenylalanine backbone homologues and their combination with functionalized carbon nanotubes. AB - The integration of carbon nanotubes (CNTs) into organized nanostructures is of great interest for applications in materials science and biomedicine. In this work we studied the self-assembly of beta and gamma homologues of diphenylalanine peptides under different solvent and pH conditions. We aimed to investigate the role of peptide backbone in tuning the formation of different types of nanostructures alone or in combination with carbon nanotubes. In spite of having the same side chain, beta and gamma peptides formed distinctively different nanofibers, a clear indication of the role played by the backbone homologation on the self-assembly. The variation of the pH allowed to transform the nanofibers into spherical structures. Moreover, the co-assembly of beta and gamma peptides with carbon nanotubes covalently functionalized with the same peptide generated unique dendritic assemblies. This comparative study on self-assembly using diphenylalanine backbone homologues and of the co-assembly with CNT covalent conjugates is the first example exploring the capacity of beta and gamma peptides to adopt precise nanostructures, particularly in combination with carbon nanotubes. The dendritic organization obtained by mixing carbon nanotubes and peptides might find interesting applications in tissue engineering and neuronal interfacing. PMID- 26359903 TI - Inflammation and immunity in schizophrenia: implications for pathophysiology and treatment. AB - Complex interactions between the immune system and the brain might have important aetiological and therapeutic implications for neuropsychiatric brain disorders. A possible association between schizophrenia and the immune system was postulated over a century ago, and is supported by epidemiological and genetic studies pointing to links with infection and inflammation. Contrary to the traditional view that the brain is an immunologically privileged site shielded behind the blood-brain barrier, studies in the past 20 years have noted complex interactions between the immune system, systemic inflammation, and the brain, which can lead to changes in mood, cognition, and behaviour. In this Review, we describe some of the important areas of research regarding innate and adaptive immune response in schizophrenia and related psychotic disorders that, we think, will be of interest to psychiatric clinicians and researchers. We discuss potential mechanisms and therapeutic implications of these findings, including studies of anti inflammatory drugs in schizophrenia, describe areas for development, and offer testable hypotheses for future investigations. PMID- 26359908 TI - Convergent synthesis of digitally-encoded poly(alkoxyamine amide)s. AB - Binary-encoded poly(alkoxyamine amide)s were prepared by oligomer ligation. These polymers contain digital sequences based on two monomers defined as 0 and 1 bits. A library of oligomers containing all possible dyads 00, 01, 10 and 11 was prepared and used to construct long coded sequences. PMID- 26359910 TI - Composite materials with enhanced dimensionless Young's modulus and desired Poisson's ratio. AB - We have designed a new type of composite materials which not only has a Young's modulus much larger than the Voigt limit, but also is always nearly isotropic. Moreover, its Poisson's ratio can be designed at a desired value, e.g. positive, or negative, or zero. We have also demonstrated that structural hierarchy can help to enhance the stiffness of this type of composite materials. The results obtained in this paper provide a very useful insight into the development of new functional materials and structures. PMID- 26359909 TI - Proteomic analysis of embryonic kidney development: Heterochromatin proteins as epigenetic regulators of nephrogenesis. AB - Elucidation of the mechanisms underlying the nephrogenesis will boost enormously the regenerative medicine. Here we performed 2-D gel-based comparative proteome analyses of rat embryonic kidney from different developmental stages. Out of 288 non-redundant identified proteins, 102 were common in all developmental stages. 86% of the proteins found in E14 and E16 were identical, in contrast only 37% of the identified proteins overlap between E14 and P1. Bioinformatics analysis suggests developmental stage-specific pathway activation and highlighted heterochromatin protein 1 (Cbx1, Cbx3, Cbx5) and Trim28 as potential key players in nephrogenesis. These are involved in the epigenetic regulation of gene silencing and were down-regulated in the course of kidney development. Trim28 is a potential epigenetic regulator of the branching inhibitor Bmp4. Silencing of Trim28 in cultured kidneys resulted in branching arrest. In contrast knockdown of Cbx5 was associated with abnormal ureteric bud growth and slight impairment of branching. ChIP analysis showed that the H3K9me3 distribution on Bmp4 promoters at E14 and E19 inversely correlate with mRNA expression levels. The concentrated expression-pattern of heterochromatin proteins and the negative impact of their silencing on kidney development, suggest an important role in reciprocal and inductive signaling between the ureteric bud and the metanephric mesenchyme. PMID- 26359911 TI - 16Stimator: statistical estimation of ribosomal gene copy numbers from draft genome assemblies. AB - The 16S rRNA gene (16S) is an accepted marker of bacterial taxonomic diversity, even though differences in copy number obscure the relationship between amplicon and organismal abundances. Ancestral state reconstruction methods can predict 16S copy numbers through comparisons with closely related reference genomes; however, the database of closed genomes is limited. Here, we extend the reference database of 16S copy numbers to de novo assembled draft genomes by developing 16Stimator, a method to estimate 16S copy numbers when these repetitive regions collapse during assembly. Using a read depth approach, we estimate 16S copy numbers for 12 endophytic isolates from Arabidopsis thaliana and confirm estimates by qPCR. We further apply this approach to draft genomes deposited in NCBI and demonstrate accurate copy number estimation regardless of sequencing platform, with an overall median deviation of 14%. The expanded database of isolates with 16S copy number estimates increases the power of phylogenetic correction methods for determining organismal abundances from 16S amplicon surveys. PMID- 26359912 TI - Activity and community structures of sulfate-reducing microorganisms in polar, temperate and tropical marine sediments. AB - Temperature has a fundamental impact on the metabolic rates of microorganisms and strongly influences microbial ecology and biogeochemical cycling in the environment. In this study, we examined the catabolic temperature response of natural communities of sulfate-reducing microorganisms (SRM) in polar, temperate and tropical marine sediments. In short-term sediment incubation experiments with (35)S-sulfate, we demonstrated how the cardinal temperatures for sulfate reduction correlate with mean annual sediment temperatures, indicating specific thermal adaptations of the dominant SRM in each of the investigated ecosystems. The community structure of putative SRM in the sediments, as revealed by pyrosequencing of bacterial 16S rRNA gene amplicons and phylogenetic assignment to known SRM taxa, consistently correlated with in situ temperatures, but not with sediment organic carbon concentrations or C:N ratios of organic matter. Additionally, several species-level SRM phylotypes of the class Deltaproteobacteria tended to co-occur at sites with similar mean annual temperatures, regardless of geographic distance. The observed temperature adaptations of SRM imply that environmental temperature is a major controlling variable for physiological selection and ecological and evolutionary differentiation of microbial communities. PMID- 26359914 TI - Anti-Mullerian hormone trend evaluation after laparoscopic surgery of monolateral endometrioma using a new dual wavelengths laser system (DWLS) for hemostasis. AB - Operative laparoscopy is the gold standard in the treatment of endometriotic ovarian cysts. Excisional surgery is the best technique to prevent recurrences and improve symptoms but it may result in ovarian reserve damage due to the removal of healthy ovarian cortex. The aim of this study was to assess the impact on ovarian reserve of the use of dual wavelengths laser system (DWLS) hemostasis after stripping technique of monolateral endometrioma, by dosing the anti Mullerian hormone (AMH). This prospective study was conducted at the Institute of Obstetrics and Gynecology, University of Foggia, from December 2013 to January 2015. Forty-five women underwent excision of monolateral endometriotic ovarian cyst by stripping without using a bipolar coagulation and performing hemostasis with a DWLS. The AMH serum levels were estimated before the surgery (T0), 4-6 weeks (T1) and 6-9 months (T2) after surgery. Our results suggest that an appropriate surgical technique with the use of laser hemostasis does not determine a significant reduction of ovarian reserve. Laser hemostasis could prevent follicular reserve loss after ovarian endometrioma surgery. PMID- 26359913 TI - The initial state of the human gut microbiome determines its reshaping by antibiotics. AB - Microbiome studies have demonstrated the high inter-individual diversity of the gut microbiota. However, how the initial composition of the microbiome affects the impact of antibiotics on microbial communities is relatively unexplored. To specifically address this question, we administered a second-generation cephalosporin, cefprozil, to healthy volunteers. Stool samples gathered before antibiotic exposure, at the end of the treatment and 3 months later were analysed using shotgun metagenomic sequencing. On average, 15 billion nucleotides were sequenced for each sample. We show that standard antibiotic treatment can alter the gut microbiome in a specific, reproducible and predictable manner. The most consistent effect of the antibiotic was the increase of Lachnoclostridium bolteae in 16 out of the 18 cefprozil-exposed participants. Strikingly, we identified a subgroup of participants who were enriched in the opportunistic pathogen Enterobacter cloacae after exposure to the antibiotic, an effect linked to lower initial microbiome diversity and to a Bacteroides enterotype. Although the resistance gene content of participants' microbiomes was altered by the antibiotic, the impact of cefprozil remained specific to individual participants. Resistance genes that were not detectable prior to treatment were observed after a 7-day course of antibiotic administration. Specifically, point mutations in beta-lactamase blaCfxA-6 were enriched after antibiotic treatment in several participants. This suggests that monitoring the initial composition of the microbiome before treatment could assist in the prevention of some of the adverse effects associated with antibiotics or other treatments. PMID- 26359915 TI - In Vitro Screening and in Silico Modeling of RNA-Based Gene Expression Control. AB - Molecular tools for controlling gene expression are essential for manipulating biological systems. One class of tools includes RNA switches that incorporate RNA based sensors, known as aptamers. However, most switches reported to date are responsive to toxic molecules or to endogenous metabolites. For effective conditional control, switches must incorporate RNA aptamers that exhibit selectivity against such endogenous metabolites. We report a systematic approach which combines a rapid in vitro assay and an in silico model to support an efficient, streamlined application of aptamers into RNA switches. Model predictions were validated in vivo and demonstrate that the RNA switches enable selective and programmable gene regulation. We demonstrate the method using aptamers that bind the FDA-approved small molecule (6R)-folinic acid, providing access to new molecular targets for gene expression control and much-needed clinically relevant tools for advancing RNA-based therapeutics. PMID- 26359916 TI - Psychiatric outcomes after pediatric sports-related concussion. AB - OBJECT: The objectives of this study were twofold: (1) to examine the prevalence of emotional symptoms among children and adolescents with a sports-related concussion (SRC) who were referred to a multidisciplinary pediatric concussion program and (2) to examine the prevalence, clinical features, risk factors, and management of postinjury psychiatric outcomes among those in this clinical population. METHODS: The authors conducted a retrospective chart review of all patients with SRC referred to a multidisciplinary pediatric concussion program between September 2013 and October 2014. Clinical assessments carried out by a single neurosurgeon included clinical history, physical examination, and Post Concussion Symptom Scale (PCSS) scoring. Postinjury psychiatric outcomes were defined as a subjective worsening of symptoms of a preinjury psychiatric disorder or new and isolated suicidal ideation or diagnosis of a novel psychiatric disorder (NPD). An NPD was defined as a newly diagnosed psychiatric disorder that occurred in a patient with or without a lifetime preinjury psychiatric disorder after a concussion. Clinical resources, therapeutic interventions, and clinical and return-to-play outcomes are summarized. RESULTS: One hundred seventy-four patients (mean age 14.2 years, 61.5% male) were included in the study. At least 1 emotional symptom was reported in 49.4% of the patients, and the median emotional PCSS subscore was 4 (interquartile range 1-8) among those who reported at least 1 emotional symptom. Overall, 20 (11.5%) of the patients met the study criteria for a postinjury psychiatric outcome, including 14 patients with an NPD, 2 patients with isolated suicidal ideation, and 4 patients with worsening symptoms of a preinjury psychiatric disorder. Female sex, a higher initial PCSS score, a higher emotional PCSS subscore, presence of a preinjury psychiatric history, and presence of a family history of psychiatric illness were significantly associated with postinjury psychiatric outcomes. Interventions for patients with postinjury psychiatric outcomes included pharmacological therapy alone in 2 patients (10%), cognitive behavioral therapy alone in 4 (20%), multimodal therapy in 9 (45%), and no treatment in 5 (25%). Overall, 5 (25%) of the patients with postinjury psychiatric disorders were medically cleared to return to full sports participation, whereas 5 (25%) were lost to follow-up and 9 (45%) remained in treatment by the multidisciplinary concussion program at the end of the study period. One patient who was asymptomatic at the time of initial consultation committed suicide. CONCLUSIONS: Emotional symptoms were commonly reported among pediatric patients with SRC referred to a multidisciplinary pediatric concussion program. In some cases, these symptoms contributed to the development of an NPD, isolated suicidal ideation, and worsening symptoms of a preexisting psychiatric disorder. Future research is needed to clarify the prevalence, pathophysiology, risk factors, and evidence-based management of postinjury psychiatric outcomes after pediatric SRC. Successful management of these patients requires prompt recognition and multidisciplinary care by experts with clinical training and experience in concussion and psychiatry. PMID- 26359917 TI - Inhibitory Effects of Isorhamnetin on the Invasion of Human Breast Carcinoma Cells by Downregulating the Expression and Activity of Matrix Metalloproteinase 2/9. AB - Matrix metalloproteinases (MMPs) play an active role in facilitating the invasion of cancer cells with excessive extracellular matrix (ECM) degradation. In the present study, we investigated the antiinvasive effects of isorhamnetin, a naturally occurring flavonoid, on MDA-MB-231 human breast carcinoma cells. The results indicated that isorhamnetin significantly inhibited the adhesion, migration, and invasion of the cells in vitro. Moreover, isorhamnetin suppressed the activity and expression of MMP-2 and MMP-9, which were determined by gelatin zymography, real-time PCR, and Western blot analysis, respectively. Besides, isorhamnetin had little effect on the secretion of urokinase plasminogen activator. Further elucidation of the mechanism revealed that isorhamnetin exerted an inhibitory effect on the phosphorylation of p38 and STAT3, although it had no effect on ERK1/2 and JNK. Taken together, these data demonstrated that isorhamnetin could significantly inhibit the invasion of MDA-MB-231 cells by downregulating the expression and activity of MMP-2 and MMP-9, which was potentially associated with the suppression of p38 MAPK and STAT3. Therefore, the findings provide new evidence for the anti-cancer activity of isorhamnetin. PMID- 26359918 TI - Beyond smoking in the boys' room: The challenges of substance abuse and misuse in U.S. schools. PMID- 26359919 TI - Fluorocarbon nanodrops as acoustic temperature probes. AB - This work investigated the use of superheated fluorocarbon nanodrops for ultrasound thermal imaging and the use of mixed fluorocarbons for tuning thermal and acoustic thresholds for vaporization. Droplets were fabricated by condensing phospholipid-coated microbubbles containing C3F8 and C4F10 mixed at various molar ratios. Vaporization temperatures first were measured in a closed system by optical transmission following either isothermal pressure release or isobaric heating. The vaporization temperature was found to depend linearly on the percentage of C4F10 in the droplet core, indicating excellent tunability under these fluorocarbon-saturated conditions. Vaporization temperatures were then measured in an open system using contrast-enhanced ultrasound imaging, where it was found that the mixed droplets behaved like pure C4F10 drops. Additionally, the critical mechanical index for vaporization was measured at the limits of therapeutic hyperthermia (37 and 60 degrees C), and again the mixed droplets were found to behave like pure C4F10 drops. These results suggested that C3F8 preferentially dissolves out of the droplet core in open systems, as shown by a simple mass transfer model of multicomponent droplet dissolution. Finally, proof of-concept was shown that pure C4F10 nanodrops can be used as an acoustic temperature probe. Overall, these results not only demonstrate the potential of superheated fluorocarbon emulsions for sonothermetry but also point to the limits of tunability for fluorocarbon mixtures owing to preferential release of the more soluble species to the atmosphere. PMID- 26359920 TI - AICAR enhances insulin signaling via downregulation of miR-29. AB - As an activator of AMPK, the effect of AICAR on insulin signaling has not been investigated extensively. PI3K-Akt is a critical node involved in the insulin signaling pathway. We observed that concomitant with the activation of AMPK by AICAR, the protein level of PI3K p85alpha and the insulin-induced phosphorylation of Akt were enhanced in mouse primary hepatocytes. Previously, we identified a group of AMPK-regulated miRNAs in hepatocytes. It is not clear whether miRNAs are related to the regulation of insulin signaling by AMPK. Here, we confirmed the negative regulation of miR-29 family members by AICAR treatment in mouse primary hepatocytes. Our results indicated that p85alpha is a direct target of miR-29 and is negatively regulated by miR-29b in hepatocytes. In agreement with the findings in vitro, we found that the expression of miR-29 and the protein levels of p85alpha were inversely correlated in the liver of fasted mice. Overexpression of miR-29b reduced the insulin-induced phosphorylation of Akt in hepatocytes, suggesting that miR-29 could serve as a negative regulator of insulin signaling. Furthermore, we found that overexpression of miR-29 could attenuate the effect of AICAR on p85alpha expression. Taken together, our results indicated that activation of AMPK may enhance insulin signaling via downregulation of miR-29. PMID- 26359921 TI - The complete mitochondrial genome of Juema pig Sus scrofa (Suina: Suidae) from southern Gansu. AB - Juema pig is a kind of rare and special pig which is well adapted to high altitude, cold climate and harsh natural environment. The complete mitochondrial genome of Juema pig Sus scrofa is a circular molecule of 16 532 bp in length, containing 13 protein-coding genes, two ribosomal RNAs, 22 transfer RNAs, and a control region. The A + T content of the overall base composition of H-strand is 60.7% (T: 26.2%; C: 26.0%; A: 34.5%; G: 13.3%). ND4L gene begins with GTG as start codon, ND2, ND3, and ND5 genes begin with ATA as a start codon, and other nine protein-coding genes start with ATG. Cyt b gene is terminated with AGA as stop codon, ND1 and ND2 genes are terminated with TAG as stop codon, COII, COIII, ND3, and ND4 end with T, while ATP6, ATP8, COI, ND4L, ND5, and ND6 end with TAA. In addition, the phylogenetic relationships from neighbor-joining analyses based on the 13 concatenated PCGs indicated (Tylopoda (Suina (Ruminantia (Hippopotamidae, Cetacea)))). PMID- 26359922 TI - When Using a Negative Gender Stereotype as an Excuse Increases Gender Stereotyping in Others. AB - Prior work has shown that women use gender stereotypes to excuse their stereotypic failures, and doing so incurs negative costs. This study examined if the audience who witnesses a woman using such a stereotypic excuse also incurs costs in the form of increased gender stereotype endorsement. Male and female participants reviewed a survey supposedly completed by a female target who recently took a math exam. In this survey, the female target either performed well or poorly on the exam, and when asked to explain her performance, either invoked a gender stereotype as an excuse (e.g., women are worse at math than men) or not. The results indicated that men (but not women) showed greater gender stereotype endorsement after reading about a female target that invoked a stereotypic excuse. These results suggest that when women use a gender stereotype as an excuse, they may unintentionally cause some observers to increase their endorsement of gender stereotypes. PMID- 26359923 TI - Minimally invasive colorectal surgery: do we all speak the same language? PMID- 26359924 TI - Ciao Vic!: In Memory of Victor W. Fazio. PMID- 26359925 TI - What colorectal surgeons should know about probiotics: a review. PMID- 26359930 TI - Progressive retinal structure abnormalities in multiple system atrophy. AB - BACKGROUND: Objective measures of disease progression that can be used as endpoints in clinical trials of MSA are necessary. We studied retinal thickness in patients with MSA and assessed changes over time to determine its usefulness as an imaging biomarker of disease progression. METHODS: This was a cross sectional study including 24 patients with MSA, 20 with PD, and 35 controls, followed by a longitudinal study of 13 MSA patients. Patients were evaluated with high-definition optical coherence tomography and the Unified Multiple System Atrophy Rating Scale. Evaluations were performed at baseline and at consecutive follow-up visits for up to 26 months. RESULTS: MSA subjects had normal visual acuity and color discrimination. Compared to controls, retinal nerve fiber layer (P = 0.008 and P = 0.001) and ganglion cell complex (P = 0.013 and P = 0.001) thicknesses were reduced in MSA and PD. No significant differences between MSA and PD were found. Over time, in patients with MSA, there was a significant reduction of the retinal nerve fiber layer and ganglion cell complex thicknesses, with estimated annual average losses of 3.7 and 1.8 MUm, respectively. CONCLUSIONS: Visually asymptomatic MSA patients exhibit progressive reductions in the thickness of the retinal nerve fiber layer and, to a lesser extent, in the macular ganglion cell complex, which can be quantified by high-definition optical coherence tomography. Specific patterns of retinal nerve fiber damage could be a useful imaging biomarker of disease progression in future clinical trials. PMID- 26359932 TI - Coolmine Therapeutic Community, Dublin: a 40-year history of Ireland's first voluntary drug treatment service. AB - AIM: To document the evolution over 40 years (from 1973 to 2013) of Coolmine Therapeutic Community (Ireland's first voluntary drug treatment service) against a background of broader drug policy developments in the Republic of Ireland and elsewhere during this period. METHODS: Data were gathered by means of archival research within Coolmine, complemented by semi-structured interviews with former clients, current and former Coolmine management and staff, and representatives of outsider stakeholder interests. RESULTS: Coolmines's history has three phases: (1) an early and uncontentious phase, in which external authorities provided financial support for Coolmine without questioning its work practices or outcomes; (2) a middle, controversial phase, in which Coolmine struggled for survival in an external policy environment now dominated by harm reduction strategies; and (3) a final phase in which, through the use of conventional corporate governance, Coolmine management sought to repair its damaged reputation by introducing evidence-based clinical practices. CONCLUSIONS: Coolmine Therapeutic Community was established when drug treatment services in Ireland were in their infancy, and its changing fortunes over subsequent decades reflected changing perceptions of what constitutes appropriate addiction treatment-and in particular the role to be played by former addicts within addiction treatment systems-as well as changing perceptions of funding relationships between statutory authorities and voluntary providers of health and social services. PMID- 26359931 TI - 5'-AMP activated protein kinase alpha2 controls substrate metabolism during post exercise recovery via regulation of pyruvate dehydrogenase kinase 4. AB - It is well known that exercise has a major impact on substrate metabolism for many hours after exercise. However, the regulatory mechanisms increasing lipid oxidation and facilitating glycogen resynthesis in the post-exercise period are unknown. To address this, substrate oxidation was measured after prolonged exercise and during the following 6 h post-exercise in 5'-AMP activated protein kinase (AMPK) alpha2 and alpha1 knock-out (KO) and wild-type (WT) mice with free access to food. Substrate oxidation was similar during exercise at the same relative intensity between genotypes. During post-exercise recovery, a lower lipid oxidation (P < 0.05) and higher glucose oxidation were observed in AMPKalpha2 KO (respiratory exchange ratio (RER) = 0.84 +/- 0.02) than in WT and AMPKalpha1 KO (average RER = 0.80 +/- 0.01) without genotype differences in muscle malonyl-CoA or free-carnitine concentrations. A similar increase in muscle pyruvate dehydrogenase kinase 4 (PDK4) mRNA expression in WT and AMPKalpha2 KO was observed following exercise, which is consistent with AMPKalpha2 deficiency not affecting the exercise-induced activation of the PDK4 transcriptional regulators HDAC4 and SIRT1. Interestingly, PDK4 protein content increased (63%, P < 0.001) in WT but remained unchanged in AMPKalpha2 KO. In accordance with the lack of increase in PDK4 protein content, lower (P < 0.01) inhibitory pyruvate dehydrogenase (PDH)-E1alpha Ser(293) phosphorylation was observed in AMPKalpha2 KO muscle compared to WT. These findings indicate that AMPKalpha2 regulates muscle metabolism post-exercise through inhibition of the PDH complex and hence glucose oxidation, subsequently creating conditions for increased fatty acid oxidation. PMID- 26359933 TI - Adaptive immune defects in a patient with leukocyte adhesion deficiency type III with a novel mutation in FERMT3. PMID- 26359934 TI - Excellent outcomes of liver transplantation using severely steatotic grafts from brain-dead donors. AB - Liver grafts with macrovesicular steatosis of > 60% are considered unsuitable for deceased donor liver transplantation (DDLT) because of the unacceptably high risk of primary nonfunction (PNF) and graft loss. This study reports our experience in using such grafts from brain-dead donors. Prospectively collected data of DDLT recipient outcomes from 1991 to 2013 were retrospectively analyzed. Macrovesicular steatosis > 60% at postperfusion graft biopsy was defined as severe steatosis. In total, 373 patients underwent DDLT. Nineteen patients received severely steatotic grafts (ie, macrovesicular steatosis > 60%), and 354 patients had grafts with <= 60% steatosis (control group). Baseline demographics were comparable except that recipient age was older in the severe steatosis group (51 versus 55 years; P = 0.03). Median Model for End-Stage Liver Disease (MELD) score was 20 in the severe steatosis group and 22 in the control group. Cold ischemia time (CIT) was 384 minutes in the severe steatosis group and 397.5 minutes in the control group (P = 0.66). The 2 groups were similar in duration of stay in the hospital and in the intensive care unit. Risk of early allograft dysfunction (0/19 [0%] versus 1/354 [0.3%]; P>0.99) and 30-day mortality (0/19 [0%] versus 11/354 [3.1%]; P = 0.93) were also similar between groups. No patient developed PNF. The 1-year and 3-year overall survival rates in the severe steatosis group were both 94.7%. The corresponding rates in the control group were 91.8% and 85.8% (P = 0.55). The use of severely steatotic liver grafts from low-risk donors was safe, and excellent outcomes were achieved; however, these grafts should be used with caution, especially in patients with high MELD score. Keeping a short CIT was crucial for the successful use of such grafts in liver transplantation. PMID- 26359935 TI - Synthesis of Amphiphilic Ru(II) Heteroleptic Complexes Based on Benzo[1,2-b:4,5 b']dithiophene: Relevance of the Half-Sandwich Complex Intermediate and Solvent Compatibility. AB - The detailed synthesis and characterization of four ruthenium(II) complexes [RuLL'(NCS)2 ] is reported, in which L represents a 2,2'-bipyridine ligand functionalized at the 4,4' positions with benzo[1,2-b:4,5-b']dithiophene derivatives (BDT) and L' is 2,2'-bipyridine-4,4'-dicarboxylic acid unit (dcbpy) (NCS=isothiocyanate). The reaction conditions were adapted and optimized for the preparation of these amphiphilic complexes with a strong lipophilic character. The photovoltaic performances of these complexes were tested in TiO2 dye sensitized solar cell (DSSC) achieving efficiencies in the range of 3-4.5 % under simulated one sun illumination (AM1.5G). PMID- 26359936 TI - Does Anticomplement Therapy Have a Role in the Management of Malignant Hypertension? PMID- 26359937 TI - Detection of oxidative hair treatment using fluorescence microscopy. AB - In assessing abstinence from drug or alcohol abuse, hair analysis plays an important role. Cosmetic hair treatment influences the content of deposited drugs which is not always detectable during analysis. Since oxidation of melanin leads to an increase in fluorescence, a microscopic method was developed to distinguish natural from cosmetically treated hair. For validation, natural hair samples were treated with different types of cosmetics and inspected by fluorescence microscopy. Hair samples from 20 volunteers with documented cosmetic treatment and as a proof of concept 100 hair samples from forensic cases were analyzed by this method. Apart from autofluorescence with excitation at 365 nm, no obvious fluorescence was observed in untreated hair samples. Tinting and a natural plant product had no influence on fluorescence, but dyeing procedures including oxidation led to a marked increase in fluorescence. Proof of cosmetic treatment was achieved in hair samples from the 20 volunteers. In 100 forensic cases, 13 samples were characterized as oxidatively treated, which was in accordance with the respective disclosure except for one case where treatment was not admitted. This fluorescence microscopic procedure proved to be fast, easy, and reliable to identify oxidatively treated hair samples, which must be considered especially in evaluating cases of negative drug results. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26359938 TI - Transcending matter: physics and ultimate meaning. AB - From the discovery of new galaxies and nearly undetectable dark energy to the quantum entanglement of particles across the universe, new findings in physics naturally elicit a sense of awe and wonder. For the founders of modern physics from Einstein and Bohr to Heisenberg, Pauli, and Bohm-a fascination with deeper questions of meaning and ultimate reality led some of them to explore esoteric traditions and metaphysics. More recently, however, physicists have largely shunned such philosophical and spiritual associations. What can contemporary physics offer us in the quest to understand our place in the universe? Has physics in some ways become a religion unto itself that rejects the search for existential meaning? Discussion of these and related questions is presented in this paper. PMID- 26359939 TI - The short-term effect of yoga ocular exercise on intra-ocular pressure. PMID- 26359941 TI - Corrigendum. PMID- 26359940 TI - Validation of the NIMH-ChEFS adolescent face stimulus set in an adolescent, parent, and health professional sample. AB - Attention to faces is a fundamental psychological process in humans, with atypical attention to faces noted across several clinical disorders. Although many clinical disorders onset in adolescence, there is a lack of well-validated stimulus sets containing adolescent faces available for experimental use. Further, the images comprising most available sets are not controlled for high- and low-level visual properties. Here, we present a cross-site validation of the National Institute of Mental Health Child Emotional Faces Picture Set (NIMH ChEFS), comprised of 257 photographs of adolescent faces displaying angry, fearful, happy, sad, and neutral expressions. All of the direct facial images from the NIMH-ChEFS set were adjusted in terms of location of facial features and standardized for luminance, size, and smoothness. Although overall agreement between raters in this study and the original development-site raters was high (89.52%), this differed by group such that agreement was lower for adolescents relative to mental health professionals in the current study. These results suggest that future research using this face set or others of adolescent/child faces should base comparisons on similarly-aged validation data. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26359942 TI - Executive functions in early childhood: the role of maternal and paternal parenting practices. AB - We investigated the association between mothers' and fathers' harsh parenting and sensitive parenting practices and child's executive functions (EF) in early childhood in 607 families. We focused on three broad dimensions of child EF: Emergent metacognition, inhibitory self-control, and flexibility measured with the parent-reported Behavior Rating Inventory of Executive Function-Preschool Version. Less sensitive parenting of the mother and harsher parenting of the father were related to lower scores of emergent metacognition and inhibitory self control. Parenting was not associated with child flexibility. This study extends previous research on the association between parenting and EF by the focus on the role of the father and demonstrates independent effects of mother and father on child EF. PMID- 26359944 TI - Scaling Laws and Ionic Current Inversion in Polyelectrolyte-Grafted Nanochannels. AB - Polyelectrolyte (PE) grafting renders incredible "smartness" to nanochannels, making it capable of applications such as ion manipulation and selection, fabrication of nanoionic diodes, flow control, and so on. In this paper, we provide scaling laws that describe the dominant factors dictating the functioning of such PE-grafted nanochannels. Through these scaling calculations, we identity the phase space for the grafting density (sigma) and the polymer size (N) that simultaneously ensures that the grafted PE molecules attain a brush-like configuration and the brush height is smaller than the nanochannel half height. More importantly, we quantify in this phase space the conditions that allow decoupling of the PE electrostatic effects from the PE entropic (elastic) and the excluded volume effects. This decoupled regime is characterized by the fact that the brush height is independent of the PE electrostatic effects. In this decoupled regime, we next calculate the nanochannel ionic current for cases where the PE charge densities depend on pH (or pOH). Our results demonstrate highly interesting current inversion phenomenon originating from the triggering of "co ion-dominated" ionic current. PMID- 26359943 TI - Derepression of MicroRNA-138 Contributes to Loss of the Human Articular Chondrocyte Phenotype. AB - OBJECTIVE: To investigate the function of microRNA-138 (miR-138) in human articular chondrocytes (HACs). METHODS: The expression of miR-138 in intact cartilage and cultured chondrocytes and the effects of miR-138 overexpression on chondrocyte marker genes were investigated. Targets of miR-138 relevant to chondrocytes were identified and verified by overexpression of synthetic miRNA mimics and inhibitors, luciferase assays, chromatin immunoprecipitation, and RNA immunoprecipitation of native argonaute 2, using quantitative polymerase chain reaction, Western blotting, and luciferase assays. RESULTS: Expression levels of miR-138 were maintained at relatively low levels in intact human cartilage but were greatly increased upon loss of the differentiated phenotype in culture, with a concomitant decrease in the major cartilage extracellular matrix component COL2A1. We showed that miR-138 is able to repress the expression of COL2A1 by directly targeting Sp-1 and hypoxia-inducible factor 2alpha (HIF-2alpha), 2 transcription factors that are essential for COL2A1 transcription. We further demonstrated a direct association of these targets with miR-138 in the RNA induced silencing complex and confirmed binding of Sp-1 to the COL2A1 promoter region in HACs. CONCLUSION: We propose that an evolutionary pressure helps to suppress expression levels of miR-138 in human cartilage, thus enabling expression of appropriate tissue-specific matrix genes. Inhibition of miR-138 may serve as a potential therapeutic strategy to maintain the chondrocyte phenotype or reduce the progression of dedifferentiation in cultured HACs. PMID- 26359945 TI - Long-Range Residual Dipolar Couplings: A Tool for Determining the Configuration of Small Molecules. AB - Together with NOE and J coupling, one-bond residual dipolar coupling (RDC), which reports on the three-dimensional orientation of an internuclear vector in the molecular frame, plays an important role in the conformation and configuration analysis of small molecules in solution by NMR spectroscopy. When the molecule has few C-H bonds, or too many bonds are in parallel, the available RDCs may not be sufficient to obtain the alignment tensor used for structure elucidation. Long range RDCs that connect nuclei over multiple bonds are normally not parallel to the single bonds and therefore complement one-bond RDCs. Herein we present a method for extracting the long-range RDC of a chosen proton or group of protons to all remotely connected carbon atoms, including non-protonated carbon atoms. Alignment tensors fitted directly to the total long-range couplings (T=J+D) enabled straightforward analysis of both the long-range and one-bond RDCs for strychnine. PMID- 26359946 TI - Hygrothermal environment may cause influenza pandemics through immune suppression. AB - Over the past few decades, climate warming has caused profound changes in our living environment, and human diseases, including infectious diseases, have also been influenced by these changes. However, it remains unclear if a warm-wet climate can influence the infectivity of influenza and result in influenza pandemics. This study focused on observations of how the hydrothermal environment influences the infectivity of the influenza virus and the resulting immunoreactions of the infected mice. We used a manual climatic box to establish the following 3 environments with different temperatures and humidity: normal environment (T: 24 +/- 1 degrees C, RH: 50% +/- 4%), wet environment (T: 24 +/- 1 degrees C, RH: 95% +/- 4%) and warm-wet environment (T: 33 +/- 1 degrees C, RH: 95% +/- 4%), and the mice were fed and maintained in these 3 different environments. After 14 days, half of the mice were infected with H1N1 (A/FM1/1/47, a lung adapted strain of the flu virus specific for the mouse lung) virus for 4 d After establishing the animal model, we observed the microstructure of the lung tissue, the Th1/Th2 T cell subsets, the Th17/Treg balance, the expression of cytokines in the peripheral blood serum and the expression of the immune recognition RLH signal pathway. The results showed that mice in different environments have different reaction. Results showed that after infection, the proportion of Th1/Th2 and Th17/Treg cells in the spleen was significantly increased, and these proportions were increased the most in the infected group kept in wet-hot conditions. After infection, the mRNA levels and protein expression of the RLH (RIG-1-like helicases) signal pathway components were up regulated while the uninfected animals in the 3 diverse environments showed no significant change. The infected mice kept in the wet and warm-wet environments showed a slight elevation in the expression of RLH pathway components compared to infected mice maintained in the normal environment. Our study suggested that the warm-wet environment may have interfered with the immune response and balance. The mice kept in the warm-wet environment displayed immune tolerance when they were exposed to the influenza virus, and the body was not able to effectively clear the virus, leading to a persistent infection. A warm-wet climate may thus be a factor that contributes to influenza pandemics, people should focus on the warm-wet climate coming and advance prepare to vaccine manufacture. PMID- 26359947 TI - Analysis of colorectal cancer glyco-secretome identifies laminin beta-1 (LAMB1) as a potential serological biomarker for colorectal cancer. AB - The high mortality rate in colorectal cancer is mostly ascribed to metastasis, but the only clinical biomarker available for disease monitoring and prognosis is the carcinoembryonic antigen (CEA). However, the prognostic utility of CEA remains controversial. In an effort to identify novel biomarkers that could be potentially translated for clinical use, we collected the secretomes from the colon adenocarcinoma cell line HCT-116 and its metastatic derivative, E1, using the hollow fiber culture system, and utilized the multilectin affinity chromatography approach to enrich for the secreted glycoproteins (glyco secretome). The HCT-116 and E1 glyco-secretomes were compared using the label free quantitative SWATH-MS technology, and a total of 149 glycoproteins were differentially secreted in E1 cells. Among these glycoproteins, laminin beta-1 (LAMB1), a glycoprotein not previously known to be secreted in colorectal cancer cells, was observed to be oversecreted in E1 cells. In addition, we showed that LAMB1 levels were significantly higher in colorectal cancer patient serum samples as compared to healthy controls when measured using ELISA. ROC analyses indicated that LAMB1 performed better than CEA at discriminating between colorectal cancer patients from controls. Moreover, the diagnostic performance was further improved when LAMB1 was used in combination with CEA. PMID- 26359948 TI - Risk of Subsequent Infection Among Patients Receiving Tumor Necrosis Factor Inhibitors and Other Disease-Modifying Antirheumatic Drugs. AB - OBJECTIVE: To describe the incidence of subsequent serious infections in patients who received systemic drug therapy after an initial serious infection. METHODS: Patients with rheumatic conditions (rheumatoid arthritis [RA], psoriatic arthritis, ankylosing spondylitis) or psoriasis who experienced a serious infection between January 1, 2006 and December 31, 2011 were identified in a claims database. Patients were required to be continuously enrolled in the Truven Health Analytics MarketScan Research Database for 12 months prior to and at least 60 days after the date of discharge or the end of intravenous antibiotic therapy for the index serious infection. Subsequent serious infection incidence rates per 100 patient-years with 95% confidence intervals (95% CIs) were calculated for up to 18 months post-index, starting 60 days post-index. Cox proportional hazards models were used to adjust for baseline demographic and clinical characteristics, treatment duration, and changes during followup. RESULTS: Among the 21,699 patients who met the inclusion criteria, the majority (84.3%) had RA. Patients who received tumor necrosis factor (TNF) inhibitor therapy after their index infection had a lower rate of subsequent serious infections (18.1 per 100 patient years for those treated with a TNF inhibitor alone and 17.3 per 100 patient-years for those treated with a TNF inhibitor plus a nonbiologic disease-modifying antirheumatic drug [DMARD]) compared with those treated with a nonbiologic DMARD alone (21.4 per 100 patient-years). Etanercept, either alone (adjusted hazard ratio [HR] 0.87, 95% CI 0.77-0.99) or in combination with a nonbiologic DMARD (adjusted HR 0.76, 95% CI 0.66-0.88), and infliximab (only in combination with a nonbiologic DMARD) (adjusted HR 0.80, 95% CI 0.67-0.95) were associated with a significantly lower risk of subsequent serious infections compared with a nonbiologic DMARD alone. CONCLUSION: We did not observe an increased risk of subsequent infection in patients who received TNF inhibitor treatment following a serious infection. The risk of a subsequent serious infection was lower in patients treated with both a TNF inhibitor and a nonbiologic DMARD compared with that in patients treated with a nonbiologic DMARD alone. PMID- 26359949 TI - Recognizing and minimizing hypoglycemia: The need for individualized care. AB - Hypoglycemia is a condition known to disrupt many everyday activities and is associated with increased risks of hospitalization, falls, motor vehicle accidents and mortality. Many patients with diabetes have an increased risk of hypoglycemia due to interventions targeting glycemic control. In these patients, hypoglycemia and fear of hypoglycemia may further reduce adherence to glucose lowering regimens, contributing to the further aggravation of diabetes-related complications. Avoiding hypoglycemia should be one of the principal goals of any treatment strategies employing agents that can induce hypoglycemia in order to prevent the occurrence of associated symptoms and consequences. The education of patients and their families is an important feature of individualized management strategies in order to prevent, mitigate and treat hypoglycemic episodes. Patients with diabetes need to be made aware of how to recognize the signs of hypoglycemia and of the simple, highly effective steps that they can take to self manage hypoglycemic episodes. Clinicians should be familiar with the risk factors for hypoglycemia, especially the profiles of the different classes of glucose lowering medications such as the sulfonylureas and insulin. This article aims to review the risk factors for hypoglycemia and its implications for patients and healthcare systems, and provide practical advice for minimizing the risk of hypoglycemia and its consequences. PMID- 26359951 TI - Analysis of swimming performance: perceptions and practices of US-based swimming coaches. AB - In elite swimming, a broad range of methods are used to assess performance, inform coaching practices and monitor athletic progression. The aim of this paper was to examine the performance analysis practices of swimming coaches and to explore the reasons behind the decisions that coaches take when analysing performance. Survey data were analysed from 298 Level 3 competitive swimming coaches (245 male, 53 female) based in the United States. Results were compiled to provide a generalised picture of practices and perceptions and to examine key emerging themes. It was found that a disparity exists between the importance swim coaches place on biomechanical analysis of swimming performance and the types of analyses that are actually conducted. Video-based methods are most frequently employed, with over 70% of coaches using these methods at least monthly, with analyses being mainly qualitative in nature rather than quantitative. Barriers to the more widespread use of quantitative biomechanical analysis in elite swimming environments were explored. Constraints include time, cost and availability of resources, but other factors such as sources of information on swimming performance and analysis and control over service provision are also discussed, with particular emphasis on video-based methods and emerging sensor-based technologies. PMID- 26359950 TI - Mevastatin ameliorates sphingosine 1-phosphate-induced COX-2/PGE2-dependent cell migration via FoxO1 and CREB phosphorylation and translocation. AB - BACKGROUND AND PURPOSE: Sphingosine 1-phosphate (S1P), an important inflammatory mediator, has been shown to regulate COX-2 production and promote various cellular responses such as cell migration. Mevastatin, an inhibitor of 3-hydroxy 3-methylglutaryl-CoA reductase (HMG-CoA), effectively inhibits inflammatory responses. However, the mechanisms underlying S1P-evoked COX-2-dependent cell migration, which is modulated by mevastatin in human tracheal smooth muscle cells (HTSMCs) remain unclear. EXPERIMENTAL APPROACH: The expression of COX-2 was determined by Western blotting, real time-PCR and promoter analyses. The signalling molecules were investigated by pretreatment with respective pharmacological inhibitors or transfection with siRNAs. The interaction between COX-2 promoter and transcription factors was determined by chromatin immunoprecipitation assay. Finally, the effect of mevastatin on HTSMC migration and leukocyte counts in BAL fluid and COX-2 expression induced by S1P was determined by a cell migration assay, cell counting and Western blot. KEY RESULTS: S1P stimulated mTOR activation through the Nox2/ROS and PI3K/Akt pathways, which can further stimulate FoxO1 phosphorylation and translocation to the cytosol. We also found that S1P induced CREB activation and translocation via an mTOR-independent signalling pathway. Finally, we showed that pretreatment with mevastatin markedly reduced S1P-induced cell migration and COX-2/PGE2 production via a PPARgamma-dependent signalling pathway. CONCLUSIONS AND IMPLICATIONS: Mevastatin attenuates the S1P-induced increased expression of COX-2 and cell migration via the regulation of FoxO1 and CREB phosphorylation and translocation by PPARgamma in HTSMCs. Mevastatin could be beneficial for prevention of airway inflammation in the future. PMID- 26359952 TI - Lung Clearance Index and Structural Lung Disease on Computed Tomography in Early Cystic Fibrosis. AB - RATIONALE: The lung clearance index is a measure of ventilation distribution derived from the multiple-breath washout technique. It has been suggested as a surrogate for chest computed tomography to detect structural lung abnormalities in individuals with cystic fibrosis (CF); however, the associations between lung clearance index and early structural lung disease are unclear. OBJECTIVES: We assessed the ability of the lung clearance index to reflect structural lung disease on the basis of chest computed tomography across the entire pediatric age range. METHODS: Lung clearance index was assessed in 42 infants (ages 0-2 yr), 39 preschool children (ages 3-6 yr), and 38 school-age children (7-16 yr) with CF before chest computed tomography and in 72 healthy control subjects. Scans were evaluated for CF-related structural lung disease using the Perth-Rotterdam Annotated Grid Morphometric Analysis for Cystic Fibrosis quantitative outcome measure. MEASUREMENTS AND MAIN RESULTS: In infants with CF, lung clearance index is insensitive to structural disease (kappa = -0.03 [95% confidence interval, 0.05 to 0.16]). In preschool children with CF, lung clearance index correlates with total disease extent. In school-age children, lung clearance index correlates with extent of total disease, bronchiectasis, and air trapping. In preschool and school-age children, lung clearance index has a good positive predictive value (83-86%) but a poor negative predictive value (50-55%) to detect the presence of bronchiectasis. CONCLUSIONS: These data suggest that lung clearance index may be a useful surveillance tool to monitor structural lung disease in preschool and school-age children with CF. However, lung clearance index cannot replace chest computed tomography to screen for bronchiectasis in this population. PMID- 26359953 TI - Dialkylthio Substitution: An Effective Method to Modulate the Molecular Energy Levels of 2D-BDT Photovoltaic Polymers. AB - Dialkylthio-substituted thienyl-benzodithiophene (BDT-DST) was designed and synthesized as a building block to modulate the molecular levels of the conjugated polymers, and three copolymers named PDST-BDD, PDST-TT and PDST-DPP were prepared and applied in polymer solar cells (PSCs). Theoretical calculations and electrochemical cyclic voltammetry (CV) measurement suggested that the dialkylthio group could decrease the molecular energy levels of the resulting polymers distinctly. The open-circuit voltage (VOC) of PSC devices based on PDST BDD, PDST-TT, and PDST-DPP are as high as 1.0, 0.98, and 0.88 V, respectively, which are ~0.15 V higher than those of the corresponding alky-substituted analogues. Moreover, the influence of the dialkylthio group on the absorption spectra, crystalline properties, hole mobilities, and blend morphologies of the polymers was also investigated. The results indicate that the dialkythio substitution is an effective method to modulate the molecular energy levels and that the BDT-DST unit has potential for constructing high-efficiency photovoltaic polymers. PMID- 26359954 TI - [The Law for Patient's Rights - Impact for the Surgeon]. PMID- 26359955 TI - Pharmacy transitions of care services in Wisconsin. PMID- 26359956 TI - Opioid overdose prevention. PMID- 26359957 TI - Patient counseling in pharmacy: Through the looking glass. PMID- 26359958 TI - Pharmacy staff perceptions and self-reported behaviors related to providing contraceptive information and counseling. AB - OBJECTIVE: To evaluate pharmacy staff perspectives of a 2-year pharmacy intervention aimed at reducing unintended pregnancy in 18- to 30-year-old women. DESIGN: Pharmacy staff completed a 48-item, self-administered paper survey consisting of scaled and open-ended questions. SETTING: 55 community pharmacies in 12 Iowa counties. PARTICIPANTS: All pharmacy staff participated, including pharmacists, pharmacy technicians, and other pharmacy employees. INTERVENTION: Online continuing education (CE) training was made available to all pharmacy staff. Promotional materials including posters, brochures, and shelf talkers were displayed in all of the pharmacies. MAIN OUTCOME MEASURES: Pharmacy staff perceptions and self-reported behaviors related to displaying posters, brochures, and shelf talkers in their pharmacies and providing contraceptive information and counseling to patients/customers. RESULTS: A total of 192 (43% return rate) pharmacy staff responded. Only 44% of respondents consistently provided contraceptive information and counseling, yet more than 90% felt that talking with patients/customers about contraceptives was easy, and more than 50% could do so privately. The study showed increased pharmacy staff desire to make this topic a priority. CONCLUSION: Community pharmacy staff can play a key role in educating and counseling young adult women about contraceptive health and pregnancy planning. This study indicates that staff are comfortable providing this service and that patients/customers are open to receiving guidance from pharmacists. However, pharmacy staff are missing additional opportunities to provide information and counseling. There is also a need for greater attention to provision of nonprescription contraceptive education. PMID- 26359959 TI - Cost analysis of a novel HIV testing strategy in community pharmacies and retail clinics. AB - OBJECTIVE: To document the cost of implementing point-of-care (POC) human immunodeficiency virus (HIV) rapid testing in busy community pharmacies and retail clinics. Providing HIV testing services in community pharmacies and retail clinics is an innovative way to expand HIV testing. The cost of implementing POC HIV rapid testing in a busy retail environment needs to be documented to provide program and policy leaders with adequate information for planning and budgeting. DESIGN: Cost analysis from a pilot project that provided confidential POC HIV rapid testing services in community pharmacies and retail clinics. SETTING: The pharmacy sites were operated under several different ownership structures (for profit, nonprofit, sole proprietorship, corporation, public, and private) in urban and rural areas. We included data from the initial six sites that participated in the project. We collected the time spent by pharmacy and retail clinic staff for pretest and posttest counseling in an activity log for time-in motion for each interaction. PARTICIPANTS: Pharmacists and retail clinic staff. INTERVENTION: HIV rapid testing. MAIN OUTCOME MEASURES: The total cost was calculated to include costs of test kits, control kits, shipping, test supplies, training, reporting, program administration, and advertising. RESULTS: The six sites trained 22 staff to implement HIV testing. A total of 939 HIV rapid tests were conducted over a median time of 12 months, of which 17 were reactive. Median pretest counseling time was 2 minutes. Median posttest counseling time was 2 minutes for clients with a nonreactive test and 10 minutes for clients with a reactive test. The average cost per person tested was an estimated $47.21. When we considered only recurrent costs, the average cost per person tested was $32.17. CONCLUSIONS: Providing POC HIV rapid testing services required a modest amount of staff time and costs that are comparable to other services offered in these settings. HIV testing in pharmacies and retail clinics can provide an additional alternative venue for increasing the availability and accessibility of HIV testing services in the United States. PMID- 26359960 TI - A comparison of the Indian Health Service counseling technique with traditional, lecture-style counseling. AB - OBJECTIVES: To compare the immediate postcounseling retention of important information using the traditional method with retention obtained using the Indian Health Service (IHS) interactive technique, and to compare the time required to counsel patients on new prescriptions using the traditional method with the time required using the IHS technique. DESIGN: A prospective, nonrandomized, observational study at four different local community pharmacies in Oregon. Two sites that used the traditional counseling model served as the control sites, while two other sites used the IHS counseling model. Only new prescriptions were included in this study. The pharmacists did not alter their counseling styles for new prescriptions for the purposes of this study. The duration of counseling between the pharmacist and patient was recorded. Immediately upon completion of counseling, patients met with the primary investigator for postcounseling knowledge assessment on indication of therapy, directions on how to take their medication properly, and expected adverse effects. SETTING: Four local community pharmacies in Oregon. PARTICIPANTS: Five hundred patients at four local community pharmacies in Oregon. INTERVENTION: Use of the IHS counseling technique. MAIN OUTCOME MEASURES: Immediate recall of key counseling points and time per counseling session. RESULTS: A total of 500 patients participated in the study. Seventy-one percent of patients counseled using the IHS technique answered all three questions correctly, compared with 33% of patients counseled using the traditional method (P <0.00). For patients who were counseled about adverse effects, 80% counseled using the IHS technique compared with 51.5% counseled using the traditional approach answered all three questions correctly. For indication of therapy, there was no evidence of a difference in the proportion of correct answers between counseling types on the reason for taking their medication (P = 0.06). Those who received IHS counseling had four times the odds of correctly answering when to take their medication and four times the odds of correctly answering all adverse effects questions. The duration of counseling methods differed by 53 seconds (128 s for IHS vs. 75 s for traditional). CONCLUSION: The interactive style of the IHS method of counseling provided significantly improved immediate memory recall compared with the traditional method. The IHS method also took longer than the traditional method. PMID- 26359961 TI - Pharmacist-provided diabetes management and education via a telemonitoring program. AB - OBJECTIVE: To assess clinical outcomes (glycosylated hemoglobin [A1C], blood pressure, and lipids) and other measurements (disease state knowledge, adherence, and self-efficacy) associated with the use of approved telemonitoring devices to expand and improve chronic disease management of patients with diabetes, with or without hypertension. SETTING: Four community health centers (CHCs) in Utah. PRACTICE DESCRIPTION: Federally qualified safety net clinics that provide medical care to underserved patients. PRACTICE INNOVATION: Pharmacist-led diabetes management using telemonitoring was compared with a group of patients receiving usual care (without telemonitoring). INTERVENTIONS: Daily blood glucose (BG) and blood pressure (BP) values were reviewed and the pharmacist provided phone follow up to assess and manage out-of-range BG and BP values. EVALUATION: Changes in A1C, BP, and low-density lipoprotein (LDL) at approximately 6 months were compared between the telemonitoring group and the usual care group. Patient activation, diabetes/hypertension knowledge, and medication adherence were measured in the telemonitoring group. RESULTS: Of 150 patients, 75 received pharmacist-provided diabetes management and education via telemonitoring, and 75 received usual medical care. Change in A1C was significantly greater in the telemonitoring group compared with the usual care group (2.07% decrease vs. 0.66% decrease; P <0.001). Although BP and LDL levels also declined, differences between the two groups were not statistically significant. Patient activation measure, diabetes/hypertension knowledge, and medication adherence with antihypertensives (but not diabetes medications) improved in the telemonitoring group. CONCLUSION: Pharmacist-provided diabetes management via telemonitoring resulted in a significant improvement in A1C in federally qualified CHCs in Utah compared with usual medical care. Telemonitoring may be considered a model for providing clinical pharmacy services to patients with diabetes. PMID- 26359962 TI - A practical guide for pharmacists to establish a transitions of care program in an outpatient setting. AB - OBJECTIVES: To improve understanding of the logistics of transitions of care (TOC) clinics and to provide guidance to pharmacists in developing and implementing a new TOC clinic or improving an existing one. SETTING: Outpatient TOC clinic within an ambulatory care practice. PRACTICE DESCRIPTION: Two general internal medicine practices collaborated with a university health system to create an interdisciplinary TOC clinic to improve quality and continuity of patient care. The clinic accommodates any patients of the practice who are not able to get an appointment with their primary care physician within 1 to 2 weeks of discharge from any hospital. Physician residents, an attending physician, a clinical pharmacist, a nurse, medical assistants, and a social worker (if necessary) are involved in the patient's care during the transition process. PRACTICE INNOVATION: Pharmacists can play a vital role in developing and implementing a TOC clinic or enhancing a current one. There are many logistical components to consider in developing a clinic, and this article provides guidance in the various steps required in creating a clinic, including support and coordination, personnel, workflow, operations, reimbursement, marketing, metrics, and measures. CONCLUSION: This tool may help pharmacists implement or enhance an outpatient TOC clinic to improve patient care, quality, and continuity. PMID- 26359963 TI - Participant satisfaction with a community-based medication synchronization program. AB - OBJECTIVE: To assess participant satisfaction with a community pharmacy-based medication synchronization program. SETTING: A single location of a grocery store pharmacy chain in the Kansas City metropolitan area. PRACTICE DESCRIPTION: A medication synchronization program, Time My Meds (TMM), was implemented in 1 of 20 community pharmacies within the grocery store chain. PRACTICE INNOVATION: Current pharmacy patients taking three or more chronic medications were recruited to enroll in the medication synchronization program. After at least 3 months of enrollment in TMM, participants were invited to complete a paper survey to assess satisfaction with the program. EVALUATION: Data were collected on overall participant satisfaction with the TMM program. A 10-statement survey gathered demographic information and assessed participant satisfaction using a 5-point Likert scale (1, strongly disagree, to 5, strongly agree). RESULTS: Data collected from 48 surveys were analyzed. No statistical differences in participant satisfaction were found when considering age, education, income, number of medications at pick-up, or number of monthly trips to the pharmacy prior to program enrollment. Median scores for individual survey items were all 5 out of 5 (strongly agree) using a 5-point Likert scale. CONCLUSION: Participants were highly satisfied with the medication synchronization program. These results, if expanded to a wider population, might provide valuable information for continued justification and implementation of this type of service in community pharmacies. PMID- 26359964 TI - Evaluation of outpatient medication reconciliation involving student pharmacists at a comprehensive cancer center. AB - OBJECTIVE: To determine the number of discrepancies and medication-related problems found as a result of pharmacy-led medication reconciliation involving introductory pharmacy practice experience (IPPE) students at a comprehensive cancer center. SETTING: Outpatient infusion center of a National Cancer Institute (NCI)-designated and National Comprehensive Cancer Network (NCCN) cancer center. PRACTICE DESCRIPTION AND INNOVATION: Third-year IPPE students contacted and completed medication reconciliation for 510 hematology/oncology patients scheduled for infusion center appointments without a coupled provider visit. IPPE students discussed the findings of the medication reconciliations with their pharmacist preceptors, who updated the medication histories in the electronic medical record (EMR) and communicated with prescribers directly about identified medication-related problems. All medication reconciliation was documented using a standardized note template in the EMR. MAIN OUTCOME MEASURES: Number of medication discrepancies found, including medication additions, medication deletions, dose changes, and herbal product additions; medication-related problems-including drug-drug interactions, untreated indications (e.g., nausea, vomiting, pain, need for prophylactic medications), failure of patients to receive prescribed medications, and adverse drug reactions-were also documented. RESULTS: Medication reconciliation was completed for 510 patients through the student pharmacist/pharmacist preceptor-led intervention during a 1-year period between January 1, 2013, and December 31, 2013. A total of 88% of patients had at least one discrepancy identified in their medication history and corrected in the EMR. In addition, 11.4% of patients had a medication-related problem identified. CONCLUSIONS: Pharmacy-led medication reconciliation identified a large number of discrepancies among our hematology/oncology patients. This intervention allowed for correction of discrepancies in the EMR leading to improved accuracy of patient medication lists. In addition, it provided a valuable learning experience for student pharmacists. PMID- 26359965 TI - Adult vaccines for individuals with human immunodeficiency virus infection. PMID- 26359966 TI - Edoxaban tosylate monohydrate, secukinumab, and suvorexant. PMID- 26359967 TI - 'In God we trust; all others bring data'. PMID- 26359968 TI - Response to: Letter to the Editor Regarding the Article "Thyrotropin Suppression Increases the Risk of Osteoporosis Without Decreasing Recurrence in ATA Low- and Intermediate-Risk Patients with Differentiated Thyroid Carcinoma". PMID- 26359969 TI - Protein Phosphatases of Pathogenic Bacteria: Role in Physiology and Virulence. AB - The role of protein phosphatases in pathogenic bacteria has been studied extensively over the last two decades. Ser/Thr and Tyr phosphatases are associated with growth and virulence of many bacteria. These phosphatases control kinase-mediated functions and return the proteins to their unmodified state. Biochemical, structural, and functional studies, in addition to extensive genetic characterization, have highlighted the importance of phosphatases in bacteria. However, questions remain regarding the mechanisms driving localization of secretory phosphatases to cellular compartments, identification of receptor phosphatase sensory signals, and a possible role of cofactors and ligands in their functions. This review focuses on the role of Ser/Thr- and Tyr-specific phosphatases present in pathogenic bacteria, with an emphasis on the regulation of basic cellular processes and virulence. Furthermore, we highlight their clinical importance and analyze the development of drugs targeting protein phosphatases. PMID- 26359970 TI - Observation of an Excitonic Quantum Coherence in CdSe Nanocrystals. AB - Recent observations of excitonic coherences within photosynthetic complexes suggest that quantum coherences could enhance biological light harvesting efficiencies. Here, we employ optical pump-probe spectroscopy with few femtosecond pulses to observe an excitonic quantum coherence in CdSe nanocrystals, a prototypical artificial light harvesting system. This coherence, which encodes the high-speed migration of charge over nanometer length scales, is also found to markedly alter the displacement amplitudes of phonons, signaling dynamics in the non-Born-Oppenheimer regime. PMID- 26359971 TI - Assessing the effect of different shapes of glyco-gold nanoparticles on bacterial adhesion and infections. AB - Achieving selective and sensitive carbohydrate-protein interactions (CPIs) using nanotechnology is an intriguing area of research. Here we demonstrate that the different shapes of gold nanoparticles (AuNPs) functionalized with monosaccharides tune the bacterial aggregations. The mechanism of aggregation revealed that the large number of surface interactions of rod shaped mannose AuNPs with E. coli ORN 178 compared with spherical and star-shaped AuNPs exhibited higher avidity and sensitivity. Moreover, such sensitive binding can be used for effective inhibition of bacterial infection of cells. PMID- 26359972 TI - Electrochemical label-free and reagentless genosensor based on an ion barrier switch-off system for DNA sequence-specific detection of the avian influenza virus. AB - This paper concerns the development of genosensors based on redox-active monolayers incorporating (dipyrromethene)2Cu(II) and (dipyrromethene)2Co(II) complexes formed step by step on a gold electrode surface. They were applied for electrochemical determination of oligonucleotide sequences related to avian influenza virus (AIV) type H5N1. A 20-mer probe (NH2-NC3) was covalently attached to the gold electrode surface via a reaction performed in the presence of ethyl(dimethylaminopropyl)carbodiimide / N-hydroxysuccinimide (EDC/NHS) between the amine group present in the probe and carboxylic groups present on the surface of the redox-active layer. Each modification step has been controlled with Osteryoung square-wave voltammetry. The genosensor incorporating the (dipyrromethene)2Cu(II) complex was able to detect a fully complementary single stranded DNA target with a detection limit of 1.39 pM. A linear dynamic range was observed from 1 to 10 pM. This genosensor displays good discrimination between three single-stranded DNA targets studied: fully complementary, partially complementary (with only six complementary bases), and totally noncomplementary to the probe. When the (dipyrromethene)2Co(II) complex was applied, a detection limit of 1.28 pM for the fully complementary target was obtained. However, this genosensor was not able to discriminate partially complementary and totally noncomplementary oligonucleotide sequences to the probe. Electrochemical measurements, using both types of genosensors in the presence of different supporting electrolytes, were performed in order to elaborate a new mechanism of analytical signal generation based on an ion barrier "switch-off" system. PMID- 26359973 TI - A Well-Hung Horse: Sired by Knowledge and Imagination. AB - For more than a century, historians of science have been spinning a philosophical roulette wheel, pondering which is more important in the creative process: imagination or knowledge. The most original scientists (and artists) in our day discover newness by blending existing knowledge with imaginative thinking. PMID- 26359974 TI - Deciphering the DNA Damage Response. AB - This year's Albert Lasker Basic Medical Research Award honors Evelyn Witkin and Stephen J. Elledge, two pioneers in elucidating the DNA damage response, whose contributions span more than 40 years. PMID- 26359975 TI - Releasing the Brakes on Cancer Immunotherapy. AB - This year's Lasker~DeBakey Clinical Research Award goes to James Allison for discovering that antibody blockade of the T cell molecule CTLA-4 unleashes the body's immune response against malignant tumors. This has led to development of multiple "immune checkpoint therapies" that are prolonging and saving the lives of thousands of cancer patients. PMID- 26359976 TI - Beginner's Luck. PMID- 26359977 TI - Accidents and Damage Control. PMID- 26359978 TI - Checkpoints. PMID- 26359979 TI - Nutrient Competition: A New Axis of Tumor Immunosuppression. AB - It is thought that cancer cells engage in Warburg metabolism to meet intrinsic biosynthetic requirements of cell growth and proliferation. Papers by Chang et al. and Ho et al. show that Warburg metabolism enables tumor cells to restrict glucose availability to T cells, suppressing anti-tumor immunity. PMID- 26359980 TI - Single-Cell Analysis: The Differences That Kill. AB - Using single-cell RNA sequencing, Avraham et al. investigate how variability in macrophage response to infection is controlled by variability within the pathogen population. They find that heterogeneous expression of the Salmonella virulence factor PhoP and subsequent cell-wall modifications lead to the bimodal induction of the interferon-response in infected macrophages. PMID- 26359981 TI - Helping the Help for CD8+ T Cell Responses. AB - Eickhoff et al. and Hor et al. use time-lapse intravital microscopy to show an unexpected choreography of CD4+ and CD8+ T cells "dancing" between different dendritic cell sub-populations during priming of cytotoxic immune responses to viruses. PMID- 26359982 TI - Melatonin Lulling Th17 Cells to Sleep. AB - In this issue, Farez et al. report that the circadian hormone melatonin, whose levels vary with seasonal changes in night length, shifts the immune response toward an anti-inflammatory state that may explain the seasonal variability of multiple sclerosis disease activity. PMID- 26359983 TI - The Touching Tail of a Mechanotransduction Channel. AB - In mechanotransduction, sensory receptors convert force into electrical signals to mediate such diverse functions as touch, pain, and hearing. In this issue of Cell, Zhang et al. present evidence that the fly NompC channel senses mechanical stimuli using its N-terminal tail as a tether between the cell membrane and microtubules. PMID- 26359984 TI - Melanoma Cell-Intrinsic PD-1 Receptor Functions Promote Tumor Growth. AB - Therapeutic antibodies targeting programmed cell death 1 (PD-1) activate tumor specific immunity and have shown remarkable efficacy in the treatment of melanoma. Yet, little is known about tumor cell-intrinsic PD-1 pathway effects. Here, we show that murine and human melanomas contain PD-1-expressing cancer subpopulations and demonstrate that melanoma cell-intrinsic PD-1 promotes tumorigenesis, even in mice lacking adaptive immunity. PD-1 inhibition on melanoma cells by RNAi, blocking antibodies, or mutagenesis of melanoma-PD-1 signaling motifs suppresses tumor growth in immunocompetent, immunocompromised, and PD-1-deficient tumor graft recipient mice. Conversely, melanoma-specific PD-1 overexpression enhances tumorigenicity, as does engagement of melanoma-PD-1 by its ligand, PD-L1, whereas melanoma-PD-L1 inhibition or knockout of host-PD-L1 attenuate growth of PD-1-positive melanomas. Mechanistically, the melanoma-PD-1 receptor modulates downstream effectors of mTOR signaling. Our results identify melanoma cell-intrinsic functions of the PD-1:PD-L1 axis in tumor growth and suggest that blocking melanoma-PD-1 might contribute to the striking clinical efficacy of anti-PD-1 therapy. PMID- 26359985 TI - Non-genomic and Immune Evolution of Melanoma Acquiring MAPKi Resistance. AB - Clinically acquired resistance to MAPK inhibitor (MAPKi) therapies for melanoma cannot be fully explained by genomic mechanisms and may be accompanied by co evolution of intra-tumoral immunity. We sought to discover non-genomic mechanisms of acquired resistance and dynamic immune compositions by a comparative, transcriptomic-methylomic analysis of patient-matched melanoma tumors biopsied before therapy and during disease progression. Transcriptomic alterations across resistant tumors were highly recurrent, in contrast to mutations, and were frequently correlated with differential methylation of tumor cell-intrinsic CpG sites. We identified in the tumor cell compartment supra-physiologic c-MET up expression, infra-physiologic LEF1 down-expression and YAP1 signature enrichment as drivers of acquired resistance. Importantly, high intra-tumoral cytolytic T cell inflammation prior to MAPKi therapy preceded CD8 T cell deficiency/exhaustion and loss of antigen presentation in half of disease progressive melanomas, suggesting cross-resistance to salvage anti-PD-1/PD-L1 immunotherapy. Thus, melanoma acquires MAPKi resistance with highly dynamic and recurrent non-genomic alterations and co-evolving intra-tumoral immunity. PMID- 26359986 TI - Reversible, Specific, Active Aggregates of Endogenous Proteins Assemble upon Heat Stress. AB - Heat causes protein misfolding and aggregation and, in eukaryotic cells, triggers aggregation of proteins and RNA into stress granules. We have carried out extensive proteomic studies to quantify heat-triggered aggregation and subsequent disaggregation in budding yeast, identifying >170 endogenous proteins aggregating within minutes of heat shock in multiple subcellular compartments. We demonstrate that these aggregated proteins are not misfolded and destined for degradation. Stable-isotope labeling reveals that even severely aggregated endogenous proteins are disaggregated without degradation during recovery from shock, contrasting with the rapid degradation observed for many exogenous thermolabile proteins. Although aggregation likely inactivates many cellular proteins, in the case of a heterotrimeric aminoacyl-tRNA synthetase complex, the aggregated proteins remain active with unaltered fidelity. We propose that most heat-induced aggregation of mature proteins reflects the operation of an adaptive, autoregulatory process of functionally significant aggregate assembly and disassembly that aids cellular adaptation to thermal stress. PMID- 26359987 TI - Melatonin Contributes to the Seasonality of Multiple Sclerosis Relapses. AB - Seasonal changes in disease activity have been observed in multiple sclerosis, an autoimmune disorder that affects the CNS. These epidemiological observations suggest that environmental factors influence the disease course. Here, we report that melatonin levels, whose production is modulated by seasonal variations in night length, negatively correlate with multiple sclerosis activity in humans. Treatment with melatonin ameliorates disease in an experimental model of multiple sclerosis and directly interferes with the differentiation of human and mouse T cells. Melatonin induces the expression of the repressor transcription factor Nfil3, blocking the differentiation of pathogenic Th17 cells and boosts the generation of protective Tr1 cells via Erk1/2 and the transactivation of the IL 10 promoter by ROR-alpha. These results suggest that melatonin is another example of how environmental-driven cues can impact T cell differentiation and have implications for autoimmune disorders such as multiple sclerosis. PMID- 26359988 TI - Targeting of Fn14 Prevents Cancer-Induced Cachexia and Prolongs Survival. AB - The cytokine TWEAK and its cognate receptor Fn14 are members of the TNF/TNFR superfamily and are upregulated in tumors. We found that Fn14, when expressed in tumors, causes cachexia and that antibodies against Fn14 dramatically extended lifespan by inhibiting tumor-induced weight loss although having only moderate inhibitory effects on tumor growth. Anti-Fn14 antibodies prevented tumor-induced inflammation and loss of fat and muscle mass. Fn14 signaling in the tumor, rather than host, is responsible for inducing this cachexia because tumors in Fn14- and TWEAK-deficient hosts developed cachexia that was comparable to that of wild-type mice. These results extend the role of Fn14 in wound repair and muscle development to involvement in the etiology of cachexia and indicate that Fn14 antibodies may be a promising approach to treat cachexia, thereby extending lifespan and improving quality of life for cancer patients. PMID- 26359989 TI - Broadly Neutralizing Antibody 8ANC195 Recognizes Closed and Open States of HIV-1 Env. AB - The HIV-1 envelope (Env) spike contains limited epitopes for broadly neutralizing antibodies (bNAbs); thus, most neutralizing antibodies are strain specific. The 8ANC195 epitope, defined by crystal and electron microscopy (EM) structures of bNAb 8ANC195 complexed with monomeric gp120 and trimeric Env, respectively, spans the gp120 and gp41 Env subunits. To investigate 8ANC195's gp41 epitope at higher resolution, we solved a 3.58 A crystal structure of 8ANC195 complexed with fully glycosylated Env trimer, revealing 8ANC195 insertion into a glycan shield gap to contact gp120 and gp41 glycans and protein residues. To determine whether 8ANC195 recognizes the CD4-bound open Env conformation that leads to co-receptor binding and fusion, one of several known conformations of virion-associated Env, we solved EM structures of an Env/CD4/CD4-induced antibody/8ANC195 complex. 8ANC195 binding partially closed the CD4-bound trimer, confirming structural plasticity of Env by revealing a previously unseen conformation. 8ANC195's ability to bind different Env conformations suggests advantages for potential therapeutic applications. PMID- 26359991 TI - Hypothalamic UDP Increases in Obesity and Promotes Feeding via P2Y6-Dependent Activation of AgRP Neurons. AB - Activation of orexigenic AgRP-expressing neurons in the arcuate nucleus of the hypothalamus potently promotes feeding, thus defining new regulators of AgRP neuron activity could uncover potential novel targets for obesity treatment. Here, we demonstrate that AgRP neurons express the purinergic receptor 6 (P2Y6), which is activated by uridine-diphosphate (UDP). In vivo, UDP induces ERK phosphorylation and cFos expression in AgRP neurons and promotes action potential firing of these neurons in brain slice recordings. Consequently, central application of UDP promotes feeding, and this response is abrogated upon pharmacologic or genetic inhibition of P2Y6 as well as upon pharmacogenetic inhibition of AgRP neuron activity. In obese animals, hypothalamic UDP content is elevated as a consequence of increased circulating uridine concentrations. Collectively, these experiments reveal a potential regulatory pathway in obesity, where peripheral uridine increases hypothalamic UDP concentrations, which in turn can promote feeding via PY6-dependent activation of AgRP neurons. PMID- 26359990 TI - Ankyrin Repeats Convey Force to Gate the NOMPC Mechanotransduction Channel. AB - How metazoan mechanotransduction channels sense mechanical stimuli is not well understood. The NOMPC channel in the transient receptor potential (TRP) family, a mechanotransduction channel for Drosophila touch sensation and hearing, contains 29 Ankyrin repeats (ARs) that associate with microtubules. These ARs have been postulated to act as a tether that conveys force to the channel. Here, we report that these N-terminal ARs form a cytoplasmic domain essential for NOMPC mechanogating in vitro, mechanosensitivity of touch receptor neurons in vivo, and touch-induced behaviors of Drosophila larvae. Duplicating the ARs elongates the filaments that tether NOMPC to microtubules in mechanosensory neurons. Moreover, microtubule association is required for NOMPC mechanogating. Importantly, transferring the NOMPC ARs to mechanoinsensitive voltage-gated potassium channels confers mechanosensitivity to the chimeric channels. These experiments strongly support a tether mechanism of mechanogating for the NOMPC channel, providing insights into the basis of mechanosensitivity of mechanotransduction channels. PMID- 26359992 TI - Dopamine Is Required for the Neural Representation and Control of Movement Vigor. AB - Progressive depletion of midbrain dopamine neurons (PDD) is associated with deficits in the initiation, speed, and fluidity of voluntary movement. Models of basal ganglia function focus on initiation deficits; however, it is unclear how they account for deficits in the speed or amplitude of movement (vigor). Using an effort-based operant conditioning task for head-fixed mice, we discovered distinct functional classes of neurons in the dorsal striatum that represent movement vigor. Mice with PDD exhibited a progressive reduction in vigor, along with a selective impairment of its neural representation in striatum. Restoration of dopaminergic tone with a synthetic precursor ameliorated deficits in movement vigor and its neural representation, while suppression of striatal activity during movement was sufficient to reduce vigor. Thus, dopaminergic input to the dorsal striatum is indispensable for the emergence of striatal activity that mediates adaptive changes in movement vigor. These results suggest refined intervention strategies for Parkinson's disease. PMID- 26359995 TI - Matrix Metalloproteinase-9 in the Culprit Coronary Artery and Myocardial No Reflow. AB - BACKGROUND: Matrix Metalloproteinases (MMPs) have been implicated in the pathogenesis of acute myocardial infarction (AMI). However, little is known about the association between MMP-9 and myocardial no-reflow. The aim of this study was to evaluate the role of MMP-9 in the culprit coronary artery as a predictor of no reflow in patients with ST-elevation AMI. METHODS: Ninety patients with ST elevation AMI who underwent emergency percutaneous coronary intervention were consecutively recruited in this study. Blood samples were obtained from the extraction catheter placed distal to the culprit lesion at the beginning of percutaneous coronary intervention. No-reflow was defined as a coronary thrombolysis in myocardial infarction flow grade <=2 after vessel reopening or thrombolysis in myocardial infarction flow 3 with a final myocardial blush grade <=2. RESULTS: No-reflow was observed in 25 patients (27.8%). Using multiple logistic regression analysis, local MMP-9 levels (odds ratio [OR] = 3.356; confidence interval [CI]: 1.441-5.881; P = 0.007) were found to be a significant risk factor of no-reflow together with lesion length (OR = 6.985; CI: 2.574 11.533; P = 0.009) and time to balloon (OR = 2.143; CI: 1.216-5.901; P = 0.042). CONCLUSIONS: Elevation of MMP-9 level in the culprit coronary artery may predict no-reflow in patients with ST-elevation AMI. PMID- 26359996 TI - Efficacy and Safety of IncobotulinumtoxinA in the Treatment of Upper Facial Lines: Results From a Randomized, Double-Blind, Placebo-Controlled, Phase III Study. AB - BACKGROUND: Treating upper facial lines (UFL)-a combination of glabellar frown lines (GFL), horizontal forehead lines (HFL), and lateral periorbital lines (LPL) is a common aesthetic practice. OBJECTIVE: To provide the first placebo controlled evidence of the efficacy and safety of incobotulinumtoxinA for UFL. METHODS: Healthy subjects (>=18 years) with moderate-to-severe GFL, HFL, and LPL on the Merz Aesthetics Scales (MAS) at maximum contraction were randomized to incobotulinumtoxinA or placebo. For incobotulinumtoxinA, 54 to 64 U were administered (GFL, 20 U; HFL, 10-20 U; LPL, 24 U). Investigator-assessed MAS scores were evaluated for each area at maximum contraction on Day 30, both separately (responder = score of "none" [0] or "mild" [1]) and combined (UFL; sum score <=3). Adverse events were recorded until 120 +/- 7 days after treatment. RESULTS: Overall, 156 subjects were treated (incobotulinumtoxinA: 105; placebo: 51). On Day 30 at maximum contraction, a significant (p <= .0001) effect of incobotulinumtoxinA versus placebo for GFL (84.5% vs 0.0%, respectively), HFL (70.9% vs 2.1%), LPL (64.1% vs 2.1%), and UFL combination (55.3% vs 0.0%) was demonstrated for investigator-assessed "none" or "mild" scores. Two cases of mild eyelid ptosis occurred with incobotulinumtoxinA. CONCLUSION: IncobotulinumtoxinA demonstrated significant efficacy in treating GFL, HFL, and LPL separately and combined, as well as a good safety profile. PMID- 26359997 TI - Aesthetic and Functional Outcomes of 2-Stage Versus 3-Stage Paramedian Forehead Flap Techniques: A 9-Year Comparative Study With Prospectively Collected Data. AB - BACKGROUND: The 3-stage forehead flap technique has been described as an aesthetic improvement after nasal reconstruction compared with the 2-stage technique. A standardized evaluation of aesthetic and functional outcomes of the 2-stage versus 3-stage paramedian forehead flap after nasal reconstruction was performed. METHODS: Between July 2003 and December 2012, 102 patients underwent either 2-stage or 3-stage paramedian forehead flap techniques. A standardized patient satisfaction questionnaire was used to assess resulting nasal appearance and function. Additionally, 2 plastic surgeons performed blinded assessments of the aesthetic outcome using a standardized photographic evaluation form. Together, these evaluations demonstrated functional and aesthetic outcomes (flap thickness, shape, color, flap hair growth, donor-site scars, and nasal symmetry). RESULTS: Functional and aesthetic outcomes according to the self-assessment questionnaire were similar between groups. On inclusion of the surgeon's evaluation, with a greater satisfaction was apparent from the reconstructed alar of the 2-stage group (Mann-Whitney U test, p = .03, Fisher exact test, p = .024, respectively). CONCLUSION: No clear evidence supported enhanced aesthetic results when the 3-stage forehead flap technique was used, especially in relation to flap thickness compared with the 2-stage technique. The 2-stage technique remains the state-of-the-art choice for nasal reconstruction, even in cases involving complex defects. LEVEL OF EVIDENCE: Therapy, Level III, and retrospective comparative study with prospectively collected data. PMID- 26359998 TI - A Randomized, Double-Blind, Placebo-Controlled Study of the Effect of a High Potency Topical Corticosteroid After Sclerotherapy for Reticular and Telangiectatic Veins of the Lower Extremities. AB - BACKGROUND: Although typically mild, transient, and expected, most adverse events (AEs) postsclerotherapy are inflammatory in nature. OBJECTIVE: To evaluate the effects of a high-potency topical corticosteroid (TC) applied immediately postsclerotherapy. MATERIALS AND METHODS: Subjects undergoing bilateral lower extremity sclerotherapy with polidocanol had extremities randomized to a single application of betamethasone dipropionate and placebo saline solutions immediately post-treatment in a double-blind manner. Adverse events were assessed for each extremity by subjects at t = 0 (preapplication) and t = 15 (15 minutes postapplication) and by an investigator at t = 0 and t = 15, and at Days 14 and 60. Subjects and investigator evaluated efficacy with a quartile improvement scale. RESULTS: Sixteen female subjects completed the study. Subjects reported no statistically significant differences in AEs between TC and placebo at either t = 0 or t = 15. Investigator scores for erythema and swelling/urtication were not significantly different between groups at the same time points. Although most subjects demonstrated 26% to 75% improvement at Day 60, results were not significantly different between extremities on subject and investigator evaluation. CONCLUSION: High-potency TC application immediately postsclerotherapy produced no statistically significant differences in subject- and investigator assessed AEs and clearance rates compared with placebo. Foam sclerotherapy with polidocanol is safe and effective for the treatment of lower extremity reticular veins. PMID- 26359999 TI - Commentary on Avoiding and Treating Blindness From Fillers: A Review of the World Literature. PMID- 26360000 TI - Feasibility and Potential Benefits of a Web-Based Intervention Delivered Acutely After Mild Traumatic Brain Injury in Adolescents: A Pilot Study. AB - BACKGROUND: There is a paucity of evidence-based interventions for mild traumatic brain injury (mTBI). OBJECTIVE: To evaluate the feasibility and potential benefits of an interactive, Web-based intervention for mTBI. SETTING: Emergency department and outpatient settings. PARTICIPANTS: Of the 21 adolescents aged 11 to 18 years with mTBI recruited from November 2013 to June 2014 within 96 hours of injury, 13 completed the program. DESIGN: Prospective, open pilot. INTERVENTION: The Web-based Self-Management Activity-restriction and Relaxation Training (SMART) program incorporates anticipatory guidance and psychoeducation, self-management and pacing of cognitive and physical activities, and cognitive behavioral principles for early management of mTBI in adolescents. MAIN MEASURES: Primary: Daily Post-Concussion Symptom Scale (PCSS). Secondary: Daily self reported ratings of activities and satisfaction survey. RESULTS: Average time from injury to baseline testing was 14.0 (standard deviation = 16.7) hours. Baseline PCSS was 23.6 (range: 0-46), and daily activity was 1.8 (range: 0-5.75) hours. Repeated-measures, generalized linear mixed-effects model analysis demonstrated a significant decrease of PCSS at a rate of 2.0 points per day that stabilized after about 2 weeks. Daily activities, screen time, and physical activity increased by 0.06 (standard error [SE] = 0.04, P = .09), 0.04 (SE = 0.02, P = .15), and 0.03 (SE = 0.02, P = .05) hours per day, respectively, over the 4-week follow-up. Satisfaction was rated highly by parents and youth. CONCLUSIONS: Self-Management Activity-restriction and Relaxation Training is feasible and reported to be helpful and enjoyable by participants. Future research will need to determine the comparative benefits of SMART and ideal target population. PMID- 26360001 TI - "Trying to Get a Grip": Language Competence and Self-Reported Satisfaction With Social Relationships Three Decades Post-Childhood Traumatic Brain Injury. AB - OBJECTIVE: (1) To investigate outcomes in language competence and self-reported satisfaction with social relationships in long-term survivors of childhood traumatic brain injury (TBI); and (2) to establish whether language competence contributes to self-reported satisfaction with social relationships decades after sustaining childhood TBI. PARTICIPANTS: Twelve females and 8 males aged 30 to 55 (mean = 39.80, standard deviation = 7.54) years who sustained a TBI during childhood and were on average 31 years postinjury (standard deviation = 9.69). An additional 20 participants matched for age, sex, handedness, years of education, and socioeconomic status constituted a control group. MAIN MEASURES: Test of Language Competence-Expanded Edition and the Quality of Life in Brain Injury questionnaire. RESULTS: Individuals with a history of childhood TBI performed significantly poorer than their non-injured peers on 2 (Ambiguous Sentences and Oral Expression: Recreating Sentences) out of the 4 Test of Language Competence Expanded Edition subtests used and on the Quality of Life in Brain Injury subscale assessing satisfaction with social relationships. In the TBI group, scores obtained on the Ambiguous Sentences subtest were found to be a significant predictor of satisfaction with social relationships, explaining 25% of the variance observed. CONCLUSIONS: The implication of high-level language skills to self-reported satisfaction with social relationships many decades post-childhood TBI suggests that ongoing monitoring of emerging language skills and support throughout the school years and into adulthood may be warranted if adult survivors of childhood TBI are to experience satisfying social relationships. PMID- 26360003 TI - Responsiveness, Minimal Detectable Change, and Minimally Clinically Important Differences for the Disorders of Consciousness Scale. AB - OBJECTIVES: To determine the responsiveness, minimal detectable change (MDC95), and minimally clinically important difference (MCID) of the Disorders of Consciousness Scale (DOCS-25) in patients with severe traumatic brain injury (TBI) and to report the percentages of patients' change scores exceeding MDC and MCID after 3 weeks of inpatient rehabilitation. SETTING: Post-acute rehabilitation hospitals. PARTICIPANTS: One hundred seventy-two patients with severe TBI. Ninety-two were included in the DOCS-25 3-week analysis. DESIGN: Retrospective cohort study. MAIN MEASURE(S): Disorders of Consciousness Scale, Glasgow Coma Scale. RESULTS: The effect size and standardized response mean of the DOCS-25 for those who improved were 0.45 and 1.3, respectively-moderate to large by Cohen criteria. The MDC95 (95% confidence interval) was 5.6. Distribution-based MCIDs for small (0.20 SD), moderate (0.33 SD), and large (0.50 SD) differences were 2.6 units, 4.4 units, and 6.6 units, respectively. The anchor-based MCID was 8.6 units. On average, patients who improved (n = 57) gained 14.5 units by week 3, exceeding the anchor-based MCID. On average, patients who did not improve (n = 35) declined by 7.2 units, which exceeds both the MDC95 and the largest distribution-based MCID. CONCLUSION(S): The DOCS-25 is a responsive, clinician-observed assessment tool for capturing change in neurobehavioral function in adults recovering from severe TBI. This is the first study to provide evidence for the size of neurobehavioral function change that might indicate meaningful recovery in patients with severe TBI. Results from this study may support future research by better informing sample size calculations for clinical trials and also assist clinicians in identifying when variation in level of consciousness is consequential enough to warrant changes in intervention. PMID- 26360002 TI - White Matter Associations With Performance Validity Testing in Veterans With Mild Traumatic Brain Injury: The Utility of Biomarkers in Complicated Assessment. AB - OBJECTIVE: Failure on performance validity tests (PVTs) is common in Veterans with histories of mild traumatic brain injury (mTBI), leading to questionable validity of clinical presentations. PARTICIPANTS: Using diffusion tensor imaging, we investigated white matter (WM) integrity and cognition in 79 Veterans with history of mTBI who passed PVTs (n = 43; traumatic brain injury [TBI]-passed), history of mTBI who failed at least 1 PVT (n = 13; TBI-failed), and military controls (n = 23; MCs) with no history of TBI. RESULTS: The TBI-failed group demonstrated significantly lower cognitive scores relative to MCs and the TBI passed group; however, no such differences were observed between MCs and the TBI passed group. On a global measure of WM integrity (ie, WM burden), the TBI-failed group showed more overall WM abnormalities than the other groups. However, no differences were observed between the MCs and TBI-passed group on WM burden. Interestingly, regional WM analyses revealed abnormalities in the anterior internal capsule and cingulum of both TBI subgroups relative to MCs. Moreover, compared with the TBI-passed group, the TBI-failed group demonstrated significantly decreased WM integrity in the corpus callosum. CONCLUSIONS: Findings revealed that, within our sample, WM abnormalities are evident in those who fail PVTs. This study adds to the burgeoning PVT literature by suggesting that poor PVT performance does not negate the possibility of underlying WM abnormalities in military personnel with history of mTBI. PMID- 26360004 TI - Vocational Rehabilitation Services and Outcomes for Transition-Age Youth With Traumatic Brain Injuries. AB - OBJECTIVE: This study examined data provided by the US Department of Education's Rehabilitation Services Administration (RSA) in an effort to evaluate the relationship between (a) demographic variables and vocational rehabilitation (VR) services and (b) the employment outcomes of transition-age youth with traumatic brain injuries. SETTING: Not applicable. PARTICIPANTS: Data for 1546 transition age youth (ie, 16-25 years of age) with traumatic brain injuries were examined. DESIGN: Purposeful selection of multivariate logistic regression was employed to analyze the data. MAIN MEASURES: Not applicable. RESULTS: Receipt of more VR services at higher expenditure levels over shorter periods of time was related to case closure in successful competitive employment status. Also, higher levels of education at the time of enrollment in the VR program (ie, bachelor's degrees or higher); nonreceipt of social security disability benefits at the time of enrollment in the VR program; and receipt of VR services such as occupational/vocational training, job search, job placement, on-the-job support, maintenance, and information/referral were associated with competitive employment outcomes. CONCLUSION: Client demographic and VR service-related variables significantly predict competitive employment outcomes for transition-age youth with traumatic brain injuries. Vocational rehabilitation services should focus on the specific interventions that are most closely associated with successful rehabilitation. PMID- 26360005 TI - Long-Term Motor Recovery After Severe Traumatic Brain Injury: Beyond Established Limits. AB - OBJECTIVE: To report neural plasticity changes after severe traumatic brain injury. SETTING: Case-control study. PARTICIPANTS: Canadian soldier, Captain Trevor Greene survived a severe open-traumatic brain injury during a 2006 combat tour in Afghanistan. DESIGN: Longitudinal follow-up for more than 6 years. MAIN MEASURES: Twelve longitudinal functional magnetic imaging (fMRI) examinations were conducted to investigate lower limb activation changes in association with clinical examination. Trevor Greene's lower limb fMRI activation was compared with control fMRI activation of (1) mental imagery of similar movement and (2) matched control subject data. RESULTS: Trevor Greene's motor recovery and corresponding fMRI activation increased significantly over time (F = 32.54, P < .001). Clinical measures of functional recovery correlated strongly with fMRI motor activation changes (r = 0.81, P = .001). By comparison, while Trevor Greene's mental imagery activated similar motor regions, there was no evidence of fMRI activation change over time. While comparable, control motor activation did not change over time and there was no significant mental imagery activation. CONCLUSION: Motor function recovery can occur beyond 6 years after severe traumatic brain injury, both in neural plasticity and clinical outcome. This demonstrates that continued benefits in physical function due to rehabilitative efforts can be achieved for many years following injury. The finding challenges current practices and assumptions in rehabilitation following traumatic brain injury. PMID- 26360006 TI - Emergency Department Evaluation of Traumatic Brain Injury in the United States, 2009-2010. AB - OBJECTIVE: To determine the dimensions of traumatic brain injury (TBI) evaluation in US emergency department (EDs) to inform potential application of novel diagnostic tests. SETTING: US EDs. PARTICIPANTS: National Hospital Ambulatory Medical Care Survey of ED visits in 2009 and 2010 where TBI was evaluated (1) and diagnosed either clinically or (2) with head computed tomographic (CT) scans. DESIGN: Retrospective cross-sectional. RESULTS: TBI was evaluated during 4.8 (95% confidence interval [CI], 4.2-5.4) million visits per year; and head CT scan was performed in 82% of TBI evaluations (3.9 [95% CI, 3.4-4.4] million visits per year). TBI was diagnosed in 52% of evaluations (2.5 [95% CI, 2.1-2.8] million visits per year). Among those who received head CT scans, 9% had CT evidence of traumatic abnormalities. Among patients evaluated for TBI who had a Glasgow Coma Scale score recorded, 94.5% were classified as having mild TBI, 2.1% as moderate TBI, and 3.5% as severe TBI. Among patients with International Classification of Diseases, Ninth Revision, Clinical Modification, codes permitting the calculation of head Abbreviated Injury Scale scores 9.0%, 85.0%, 2.5%, 3.2%, 0.3%, and 0% had head Abbreviated Injury Scale scores of 1, 2, 3, 4, 5, and 6, respectively. Of patients evaluated for TBI, 31% had other head/face/neck injuries, 10% had spine and back injuries, 7% had torso injuries, and 14% had extremity injuries. CONCLUSION: The ED is the main gateway to medical care for millions of patients evaluated for TBI each year. Novel diagnostic tests are needed to improve ED diagnosis and management of TBI. PMID- 26360007 TI - Persistent Hypogonadotropic Hypogonadism in Men After Severe Traumatic Brain Injury: Temporal Hormone Profiles and Outcome Prediction. AB - OBJECTIVE: To (1) examine relationships between persistent hypogonadotropic hypogonadism (PHH) and long-term outcomes after severe traumatic brain injury (TBI); and (2) determine whether subacute testosterone levels can predict PHH. SETTING: Level 1 trauma center at a university hospital. PARTICIPANTS: Consecutive sample of men with severe TBI between 2004 and 2009. DESIGN: Prospective cohort study. MAIN MEASURES: Post-TBI blood samples were collected during week 1, every 2 weeks until 26 weeks, and at 52 weeks. Serum hormone levels were measured, and individuals were designated as having PHH if 50% or more of samples met criteria for hypogonadotropic hypogonadism. At 6 and 12 months postinjury, we assessed global outcome, disability, functional cognition, depression, and quality of life. RESULTS: We recruited 78 men; median (interquartile range) age was 28.5 (22-42) years. Thirty-four patients (44%) had PHH during the first year postinjury. Multivariable regression, controlling for age, demonstrated PHH status predicted worse global outcome scores, more disability, and reduced functional cognition at 6 and 12 months post-TBI. Two step testosterone screening for PHH at 12 to 16 weeks postinjury yielded a sensitivity of 79% and specificity of 100%. CONCLUSION: PHH status in men predicts poor outcome after severe TBI, and PHH can accurately be predicted at 12 to 16 weeks. PMID- 26360009 TI - Diode laser treatment and clinical management of multiple oral lesions in patients with hereditary haemorrhagic telangiectasia. AB - Hereditary haemorrhagic telangiectasia (HHT) is rare, and characterised by vascular dysplasia that leads to various symptoms including visceral arteriovenous malformations and mucocutaneous telangiectatic lesions. Our aim was to describe the clinical features and options for the treatment of multiple oral lesions, and to illustrate the efficacy of the diode laser in the treatment of early (<2mm) and advanced lesions (2mm or more). We report 24 patients with 1200 oral telangiectatic lesions, which were often associated with regular bleeding (from monthly to daily), superinfection, pain, and swelling, and treated with multiple sessions of laser according to the number and size of the lesions. Early lesions were treated with a single laser impulse in ultrapulsed mode, and advanced lesions with repeated laser impulses in pulsed mode (t-on 200ms/t-off 500ms), at a power of 8W. Early lesions healed completely after laser photocoagulation with no operative or postoperative complications, while advanced lesions improved with a remarkable reduction in size but more discomfort. Protective occlusal plates were sometimes used to reduce the incidence of new lesions caused by dental trauma. The treatment of oral telangiectatic lesions is still being debated, and it is important to improve quality of life for patients. Diode laser surgery could be an effective treatment for oral lesions in those with hereditary haemorrhagic telangiectasia. PMID- 26360008 TI - White Matter Microstructural Compromise Is Associated With Cognition But Not Posttraumatic Stress Disorder Symptoms in Military Veterans With Traumatic Brain Injury. AB - OBJECTIVE: To investigate white matter microstructure compromise in Veterans with a history of traumatic brain injury (TBI) and its possible contribution to posttraumatic stress disorder (PTSD) symptomatology and neuropsychological functioning via diffusion tensor imaging. PARTICIPANTS AND METHODS: Thirty-eight Veterans with mild (n = 33) and moderate (n = 5) TBI and 17 military control participants without TBI completed neuropsychological testing and psychiatric screening and underwent magnetic resonance imaging an average of 4 years following their TBI event(s). Fractional anisotropy (FA) and diffusivity measures were extracted from 9 white matter tracts. RESULTS: Compared with military control participants, TBI participants reported higher levels of PTSD symptoms and performed worse on measures of memory and psychomotor-processing speed. Traumatic brain injury was associated with lower FA in the genu of the corpus callosum and left cingulum bundle. Fractional anisotropy negatively correlated with processing speed and/or executive functions in 7 of the 8 tracts. Regional FA did not correlate with memory or PTSD symptom ratings. CONCLUSION: Results suggest that current PTSD symptoms are independent of TBI-related white matter alterations, as measured by diffusion tensor imaging. In addition, white matter microstructural compromise may contribute to reduced processing speed in our sample of participants with history of neurotrauma. Findings of the current study add insight into the factors associated with complicated recovery from mild to moderate TBI. PMID- 26360010 TI - Real-time vascular imaging and photodynamic therapy efficacy with micelle nanocarrier delivery of chlorin e6 to the microenvironment of melanoma. AB - BACKGROUND: Strategies combining anti-vascular therapy and vascular imaging may facilitate the prediction of early response and outcome in cancer treatment. OBJECTIVE: The aim of this study was to investigate the relationship between the tumor-associated vasculature in melanoma and to develop an approach for melanoma treatment by utilizing the free form and micelle form of the photosensitizer (PS) chlorin e6 in photodynamic therapy (PDT). METHODS: Green fluorescence protein (GFP) expressing B16-F10 melanoma cells were implanted into the mouse ear dermis. Ce6 in free form or in micelle form was administered via the tail vein. An OV100 imaging system was used to record the red fluorescence of Ce6 to obtain real-time vascular images in the GFP tumor. RESULTS: Compared to free Ce6, Ce6 linked to the micelle-nanocarrier depicted a much clearer vascular image and had an effective vascular destruction by PDT. Micelle Ce6 was localized in lysosomes and in the endoplasmic reticulum of cultured endothelial cells, implying an active endocytosis of the nano-carrier. CONCLUSION: Micelle Ce6 can serve as a bifunctional PS for vascular imaging and PDT, which facilitates its delivery in the tumor microenvironment. PMID- 26360011 TI - Common variants of OPA1 conferring genetic susceptibility to leprosy in Han Chinese from Southwest China. AB - BACKGROUND: Leprosy is an ancient chronic infection caused by Mycobacterium leprae. Onset of leprosy was highly affected by host nutritional condition and energy production, (partially) due to genomic loss and parasitic life style of M. leprae. The optic atrophy 1 (OPA1) gene plays an essential role in mitochondria, which function in cellular energy supply and innate immunity. OBJECTIVE: To investigate the potential involvement of OPA1 in leprosy. METHODS: We analyzed 7 common genetic variants of OPA1 in 1110 Han Chinese subjects with and without leprosy, followed by mRNA expression profiling and protein-protein interaction (PPI) network analysis. RESULTS: We observed positive associations between OPA1 variants rs9838374 (Pgenotypic=0.003) and rs414237 (Pgenotypic=0.002) with lepromatous leprosy. expression quantitative trait loci (eQTL) analysis showed that the leprosy-related risk allele C of rs414237 is correlated with lower OPA1 mRNA expression level. Indeed, we identified a decrease of OPA1 mRNA expression in both with patients and cellular model of leprosy. In addition, the PPI analysis showed that OPA1 protein was actively involved in the interaction network of M. leprae induced differentially expressed genes. CONCLUSION: Our results indicated that OPA1 variants confer risk of leprosy and may affect OPA1 expression, mitochondrial function and antimicrobial pathways. PMID- 26360012 TI - Ester-free thiol-ene dental restoratives--Part B: Composite development. AB - OBJECTIVES: To assess the performance of thiol-ene dental composites based on selected ester-free thiol-ene formulations. Further, to point out the benefits/drawback of having a hydrolytically stable thiol-ene matrix within a glass filled composite. METHODS: Composite samples containing 50-65wt% of functionalized glass microparticles were prepared and photopolymerized in the presence of a suitable visible light photoinitiator. Shrinkage stress measurements were conducted as a function of the irradiation time. Degrees of conversion were measured by FT-IR analysis by comparing the double bond signals before and after photopolymerization. Mechanical tests were carried out on specimens after curing as well as after extended aging in water. Dynamic mechanical analysis was employed to track the changes in storage modulus near body temperature. The properties of the thiol-ene composites were compared with those of the BisGMA/TEGDMA control. RESULTS: Depending on the resin type, similar or higher conversions were achieved in thiol-ene composites when compared to the dimethacrylate controls. At comparable conversions, lower shrinkage stress values were achieved. Although exhibiting lower initial elastic moduli, the thiol-ene composites' flexural strengths were found to be comparable with the controls. Contrary to the control, the mechanical properties of the ester-free thiol-ene composites were shown to be unaffected by extensive aging in water and at least equaled that of the control after aging in water for just five weeks. SIGNIFICANCE: Employing non-degradable step-growth networks as organic matrices in dental composites will provide structurally uniform, tough materials with extended service time. PMID- 26360013 TI - Ester-free thiol-ene dental restoratives--Part A: Resin development. AB - OBJECTIVES: To detail the development of ester-free thiol-ene dental resins with enhanced mechanical performance, limited potential for water uptake/leachables/degradation and low polymerization shrinkage stress. METHODS: Thiol-terminated oligomers were prepared via a thiol-Michael reaction and a bulky tetra-allyl monomer containing urethane linkages was synthesized. The experimental oligomers and/or monomers were photopolymerized using visible light activation. Several thiol-ene formulations were investigated and their performance ranked by comparisons of the thermo-mechanical properties, polymerization shrinkage stress, water sorption/solubility, and reactivity with respect to a control comprising a conventional BisGMA/TEGDMA dental resin. RESULTS: The ester-free thiol-ene formulations had significantly lower viscosities, water sorption and solubility than the BisGMA/TEGDMA control. Depending on the resin, the limiting functional conversions were equivalent to or greater than that of BisGMA/TEGDMA. At comparable conversions, lower shrinkage stress values were achieved by the thiol-ene systems. The polymerization shrinkage stress was dramatically reduced when the tetra-allyl monomer was used as the ene in ester-free thiol-ene mixtures. Although exhibiting lower Young's modulus, flexural strength, and glass transition temperatures, the toughness values associated with thiol-ene resins were greater than that of the BisGMA/TEGDMA control. In addition, the thiol-ene polymerization resulted in highly uniform polymer networks as indicated by the narrow tan delta peak widths. SIGNIFICANCE: Employing the developed thiol-ene resins in dental composites will reduce shrinkage stress and moisture absorption and form tougher materials. Furthermore, their low viscosities are expected to enable higher loadings of functionalized micro/nano-scale filler particles relevant for practical dental systems. PMID- 26360014 TI - Depression and Quality of Life in Older Persons: A Review. AB - BACKGROUND: Depression is a prevalent and disabling condition in older persons (>= 60 years) that increases the risk of mortality and negatively influences quality of life (QOL). The relationship between depression, or depressive symptoms, and QOL has been increasingly addressed by research in recent years, but a review that can contribute to a better understanding of this relationship in older persons is lacking. Against this background, we undertook a literature review to assess the relationship between depression and QOL in older persons. SUMMARY: Extensive electronic database searches revealed 953 studies. Of these, 74 studies fulfilled our criteria for inclusion, of which 52 were cross-sectional studies and 22 were longitudinal studies. Thirty-five studies were conducted in a clinical setting, while 39 were community-based epidemiological studies. A clear definition of the QOL concept was described in 25 studies, and 24 different assessment instruments were employed to assess QOL. Depressed older persons had poorer global and generic health-related QOL than nondepressed individuals. An increase in depression severity was associated with a poorer global and generic health-related QOL. The associations appeared to be stable over time and independent of how QOL was assessed. KEY MESSAGES: This review found a significant association between severity of depression and poorer QOL in older persons, and the association was found to be stable over time, regardless which assessment instruments for QOL were applied. The lack of a definition of the multidimensional and multilevel concept QOL was common, and the large variety of QOL instruments in various studies make a direct comparison between the studies difficult. PMID- 26360015 TI - Clinical response to long term enzyme replacement treatment in children, adolescent and adult patients with Hunter syndrome. AB - BACKGROUND AND OBJECTIVE: Since enzyme replacement treatment (ERT) with idursulfase is available for Hunter syndrome (HS; mucopolysaccharidosis type II), for the first time, disease progression can be limited and organ damage reduced or prevented. PATIENTS AND METHODS: We described retrospectively the clinical evolution of eight HS males, treated with ERT and followed in routine clinical practice in Hospital Infantil La Fe (Valencia, Spain). RESULTS: We studied three children, three adolescents and two adults. Time from diagnosis to ERT ranged from 13.7 to 0.2 years, and duration of ERT ranged from 24 to 77.1 months. From the start of ERT, weight and height increased in children and adolescents and remained stable in adults. Glycosaminoglycans (GAG) decreased in all patients; in patient 5 (aged 23 years), we observed the highest reduction (86%) with recovery of carpal tunnel syndrome, splenomegaly and a decrease in nocturnal oxygen dependence. CONCLUSION: Our results show that ERT improve respiratory impairment and organomegalies and decrease GAGs levels in all patients including children, adolescent and adults. While cardiac manifestations and facial features stabilized, responses in other parameters were heterogeneous. PMID- 26360016 TI - Metagenomic analysis for detecting pathogens in culture-negative infective endocarditis. AB - Pathogen identification is important for proper diagnosis and optimal treatment of infective endocarditis (IE). Blood and valve cultures are the gold standard for detecting pathogens responsible for IE. However, these tests only detect culturable pathogens, and have low sensitivity, especially in patients previously treated with antibiotics. Culture-negative IE is still a major clinical problem and a diagnostic challenge. Recently, metagenomic analysis using next generation sequencing has been used to detect pathogens directly from clinical samples. However, there are very few reports of the use of metagenomic analysis for pathogen identification in culture-negative IE cases and the usefulness of this new method is unknown. Here, we report a case of successful pathogen detection with metagenomic analysis in a patient of culture-negative IE. The patient underwent valve replacement surgery and received antibiotics for 5 weeks and survived. Using metagenomic analysis of resected vegetation, we detected Abiotrophia defectiva, which is often associated with culture-negative IE due to its fastidious growth. This method may be useful for pathogen identification in future cases of culture-negative IE. PMID- 26360017 TI - Does diabetes mellitus have an impact on the prognosis for patients with cervical cancer? AB - OBJECTIVE: To evaluate the impact of comorbid diabetes mellitus (DM) on prognoses among patients with cervical cancer. METHODS: We analyzed cervical cancer outcomes in patients who treated in two hospitals retrospectively. Patients were divided into those with DM and those without. Clinicopathologic parameters, disease-free survival (DFS), and overall survival (OS) rates were evaluated. RESULTS: Of the 494 patients, 50 had DM. These were more likely to be older than those in the non-DM group and their body mass index (BMI) was higher. They showed higher levels of tumor markers and had more combined diseases. They were less likely to have had surgical treatment. Among these patients, 12 (24%) experienced a recurrence (hazard ratio, HR, 1.484; 95% confidence interval, CI, 0.746-2.951). Differences in DFS did not show statistical significance. In the OS analysis, 11 (22%) in the DM group and 62 (14%) in the non-DM group died (HR, 1.239; 95% CI, 0.606-2.533). No statistically significant differences were also observed for cancer-specific death (HR, 1.246; 95% CI, 0.567-2.737). Those with DM and an adenocarcinoma tended to have an increased risk of dying compared with the non-DM patients with an adenocarcinoma (HR, 3.673; 95% CI, 0.990-13.625), but this difference was not statistically significant (p=0.0518). CONCLUSION: Diabetes mellitus did not have an impact on the prognosis for patients with cervical cancers. In those with an adenocarcinoma, patients with diabetes tended to have an increased risk of dying compared with the non-DM group, but this difference was not statistically significant. PMID- 26360018 TI - [Developmental dysplasia of the hip in children with a psychomotor disorder. A risk factor for a poor outcome?]. AB - INTRODUCTION: Orthopaedic treatment of developmental dysplasia of the hip (DDH) has a high success rate in cases that are diagnosed early. However, the outcomes of these patients are not really known when they are subsequently diagnosed with some type of cerebral impairment. MATERIALS AND METHODS: A retrospective observational study was conducted on cases of DDH with a poor outcome after orthopaedic treatment, being unknown if they had any type of psychomotor disorder. The patients were clinically and radiologically assessed, and afterwards received neurological valuation by the Child Neurology Unit. RESULTS: Of the 325 cases of DDH diagnosed in 293 patients, 10 patients (3%) with 16 hips with DDH were diagnosed of any cerebral impairment. All them were initially treated orthopedically. Clinical and radiologically evolution was succesful only in 4 cases (25%) being necessary any surgical procedure in the remaining 12 cases. After surgical treatment we got an improvement in the Acetabular Index (p=0.005) and Reimers Extrusion Index (p=0.042). Neck-shaft angle and Wiberg CE angle also improved but this difference was not statically significant. Cerebral impairment was diagnosed at 2,5 years of age and the begining of walking was delayed at 2.4 years of age. CONCLUSIONS: Cerebral impairment can lead to an unfavourable outcome in the treatment of DDH, with the relative risk of a poor outcome being 7.2 times higher in these patients. An unfavourable outcome with conventional treatment of DDH must make us suspect the presence of some type of neurological disorder, particularly if there is a delay in walking. PMID- 26360019 TI - Urinary Concentrations of Bisphenol A and Three Other Bisphenols in Convenience Samples of U.S. Adults during 2000-2014. AB - Because of regulatory actions and public concerns, the use of bisphenol A (BPA) may decrease, while the use of BPA alternatives may increase. Although BPA alternatives are considered safer than BPA, their effects on health are still largely unknown. For risk assessment, understanding exposure to these chemicals is necessary. We measured the urinary concentrations of BPA and three bisphenol analogs, bisphenol S (BPS), bisphenol F (BPF), and bisphenol AF (BPAF), in 616 archived samples collected from convenience samplings of U.S. adults at eight time points between 2000 and 2014. We detected BPA at the highest frequency and geometric mean (GM) concentrations (74-99%, 0.36-2.07 MUg/L), followed by BPF (42 88%, 0.15-0.54 MUg/L) and BPS (19-74%, < 0.1-0.25 MUg/L); BPAF was rarely detected (<3% of all samples). Although concentrations of BPF were generally lower than for other bisphenols, the 95th percentile concentration of BPF was often comparable or higher than that of BPA. We did not observe obvious exposure trends for BPF. However, the significant changes in GM concentrations of BPA and BPS suggest that exposures may be declining (BPA) or on the rise (BPS). Nationally representative data will be useful to confirm these findings and to allow monitoring future exposure trends to BPA and some of its bisphenol alternatives. PMID- 26360020 TI - Nitric Oxide-Mediated Modulation of Central Network Dynamics during Olfactory Perception. AB - Nitric oxide (NO) modulates the dynamics of central olfactory networks and has been implicated in olfactory processing including learning. Land mollusks have a specialized olfactory lobe in the brain called the procerebral (PC) lobe. The PC lobe produces ongoing local field potential (LFP) oscillation, which is modulated by olfactory stimulation. We hypothesized that NO should be released in the PC lobe in response to olfactory stimulation, and to prove this, we applied an NO electrode to the PC lobe of the land slug Limax in an isolated tentacle-brain preparation. Olfactory stimulation applied to the olfactory epithelium transiently increased the NO concentration in the PC lobe, and this was blocked by the NO synthase inhibitor L-NAME at 3.7 mM. L-NAME at this concentration did not block the ongoing LFP oscillation, but did block the frequency increase during olfactory stimulation. Olfactory stimulation also enhanced spatial synchronicity of activity, and this response was also blocked by L-NAME. Single electrical stimulation of the superior tentacle nerve (STN) mimicked the effects of olfactory stimulation on LFP frequency and synchronicity, and both of these effects were blocked by L-NAME. L-NAME did not block synaptic transmission from the STN to the nonbursting (NB)-type PC lobe neurons, which presumably produce NO in an activity-dependent manner. Previous behavioral experiments have revealed impairment of olfactory discrimination after L-NAME injection. The recording conditions in the present work likely reproduce the in vivo brain state in those behavioral experiments. We speculate that the dynamical effects of NO released during olfactory perception underlie precise odor representation and memory formation in the brain, presumably through regulation of NB neuron activity. PMID- 26360022 TI - Correction: ZFC3H1, a Zinc Finger Protein, Modulates IL-8 Transcription by Binding with Celastramycin A, a Potential Immune Suppressor. PMID- 26360021 TI - Genome-Wide Transcription Study of Cryptococcus neoformans H99 Clinical Strain versus Environmental Strains. AB - The infection of Cryptococcus neoformans is acquired through the inhalation of desiccated yeast cells and basidiospores originated from the environment, particularly from bird's droppings and decaying wood. Three environmental strains of C. neoformans originated from bird droppings (H4, S48B and S68B) and C. neoformans reference clinical strain (H99) were used for intranasal infection in C57BL/6 mice. We showed that the H99 strain demonstrated higher virulence compared to H4, S48B and S68B strains. To examine if gene expression contributed to the different degree of virulence among these strains, a genome-wide microarray study was performed to inspect the transcriptomic profiles of all four strains. Our results revealed that out of 7,419 genes (22,257 probes) examined, 65 genes were significantly up-or down-regulated in H99 versus H4, S48B and S68B strains. The up-regulated genes in H99 strain include Hydroxymethylglutaryl-CoA synthase (MVA1), Mitochondrial matrix factor 1 (MMF1), Bud-site-selection protein 8 (BUD8), High affinity glucose transporter 3 (SNF3) and Rho GTPase-activating protein 2 (RGA2). Pathway annotation using DAVID bioinformatics resource showed that metal ion binding and sugar transmembrane transporter activity pathways were highly expressed in the H99 strain. We suggest that the genes and pathways identified may possibly play crucial roles in the fungal pathogenesis. PMID- 26360023 TI - Anti-Inflammatory Effects of IL-27 in Zymosan-Induced Peritonitis: Inhibition of Neutrophil Recruitment Partially Explained by Impaired Mobilization from Bone Marrow and Reduced Chemokine Levels. AB - Rapid activation of the innate immune system is critical for an efficient host response to invading pathogens. However, the inflammatory reaction has to be strictly controlled to minimize harmful immunopathology. A number of mediators including the cytokine interleukin-27 (IL-27) appear to be responsible for limitation and resolution of inflammation. Despite increasing knowledge of its suppressive effects on T cells, the influence on neutrophils and macrophages is poorly understood. To determine the role of IL-27 in innate immune responses we analysed the effect of IL-27 in a T cell independent model of zymosan-induced peritonitis. Early administration of recombinant IL-27 strongly reduced the number of neutrophils recruited to the peritoneal cavity after zymosan application as well as the neutrophil frequency in the blood. Simultaneously, IL 27 reduced the release of neutrophils from the bone marrow upon inflammation. Although cytokine levels were not affected by IL-27 treatment, the levels of the chemokines KC, MCP-1 and MIP-1alpha in the peritoneal fluid were strongly decreased. These findings demonstrate that IL-27 is able to control mobilisation and recruitment of neutrophils into the peritoneal cavity and identify a novel mechanism to limit inflammation caused by innate immune cells. PMID- 26360024 TI - Dynamic imaging of the recycling endosomal network in macrophages. AB - Recycling endosomes (REs) form an extensive and complex network of subcompartmentalized vesicular and tubular elements that connect with the cell surface and other endosomes in macrophages. As surveillance and defense cells of the innate immune system, macrophages are highly dependent on REs for their active and voluminous cell surface turnover and endocytic, exocytic, and recycling of membrane and cargo. Here we set out three approaches for imaging and analyzing REs in macrophages, based on the expression of fluorescently labeled RE associated proteins and the uptake of fluorescent cargo. Subcompartments of the REs are identified by co-expression and co-localization analysis of RE associated Rab GTPases. Transferrin is a well-known cargo marker as it recycles through REs and it is compared here to other cargo, revealing how different endocytic routes intersect with REs. We show how the movement of transferrin through REs can be modeled and quantified in live cells. Finally, since phagosomes are a signature organelle for macrophages, and REs fuse with the maturing phagosome, we show imaging of REs with phagosomes using a genetically encoded pH-sensitive SNARE based probe. Together these approaches provide multiple ways to comprehensively analyze REs and the important roles they play in these immune cells and more broadly in other cell types. PMID- 26360025 TI - Analyzing the functions of Rab11-effector proteins during cell division. AB - Recycling endosomes recently have emerged as major regulators of cytokinesis and abscission steps of cell division. Rab11-endosomes in particular were shown to transport proteins to the mitotic ingression furrow and play a key role in establishing the abscission site. Rab11 GTPase functions by binding and activating various effector proteins, such as Rab11 family interacting proteins (FIPs). FIPs appear to be at the core of many Rab11 functions, with FIP3 playing a role in targeting of the Rab11-endosomes during mitosis. Here we summarize the newest finding regarding the roles and regulation of FIP3 and Rab11 complex, as well as describe the methods developed to analyze membrane and cytoskeleton dynamics during abscission step of cytokinesis. PMID- 26360026 TI - Expression and localization of exocytic and recycling Rabs from Magnaporthe oryzae in mammalian cells. AB - Rab GTPases are master regulators of intracellular membrane trafficking along endocytic and exocytic pathways. In this chapter, we began to characterize the exocytic and recycling Rabs from the filamentous fungus Magnaporthe oryzae (M. oryzae) that causes the rice blast disease. Among the 11 putative Rabs identified from the M. oryzae genome database (MoRabs), MoRab1, MoRab8, and MoRab11 appear orthologs of mammalian Rab1, Rab8, and Rab11 and likely function in exocytosis and endosomal recycling. To test this contention, we cloned, expressed, and determined intracellular localization of the three MoRabs in mammalian cells, in comparison to their human counterparts (hRabs). The MoRabs were well expressed as GFP fusion proteins and colocalized with the tdTomato-labeled hRabs on exocytic and recycling organelles, as determined by immunoblot analysis and confocal fluorescence microscopy. The colocalization supports the contention that the MoRabs are indeed Rab orthologs and may play important roles in the development and pathogenicity of M. oryzae. PMID- 26360027 TI - Methods to analyze novel liaisons between endosomes and centrosomes. AB - For some time, it has been known that recycling endosomes (REs) are organized in a nebulous "pericentrosomal" region in interphase cells. However, the collective use of previously developed methods, including centrosome isolation, live cell imaging, and electron microscopy, suggested that there is much more going on between the centrosome and the RE than previously imagined. By exploiting these approaches, we uncovered novel roles of the centrosome in RE function and, conversely, novel roles for REs in centrosome function. We first found that REs dynamically localized to the centrosome throughout the cell cycle. More specifically, we found that REs interacted with appendages of the older centriole in interphase cells to control endosome recycling, and this interaction was governed by RE-machinery including the small GTPase Rab11. We next determined that REs carry centrosome proteins to spindle poles as part of the "centrosome maturation" process. Here we discuss the methods used and materials needed to complete these types of studies. PMID- 26360028 TI - Biochemical analysis of Rabin8, the guanine nucleotide exchange factor for Rab8. AB - The Rab GTPases are master regulators of endosomal trafficking in eukaryotic cells. Among them, Rab8 plays an important role in tubulovesicular trafficking from the trans-Golgi network and recycling endosomes to the plasma membrane. Rab8 is activated by its guanine nucleotide exchange factor, Rabin8. In order to understand the molecular mechanisms that control endosomal recycling to the plasma membrane, it is pivotal to understand how Rabin8 is regulated in cells. Recently, biochemical and cell biological studies have identified several mechanisms for Rabin8 activation, which involves the relief of the intramolecular autoinhibition of Rabin8. Here we describe biochemical methods that we have used recently to study the activation of Rabin8. PMID- 26360029 TI - Simple in vitro assay of Arf GAPs and preparation of Arf proteins as substrates. AB - Defining the interaction of Arf GAPs with specific Arfs is important for understanding their functions in the endocytic system. Cell-based approaches have been valuable for identifying Arfs and Arf GAPs active in the endocytic compartment; however, the cell-based assays have some limitations in establishing relationships among the Arfs and ArfGAPs. Here we describe a simple in vitro assay that will provide a means for comparing Arfs as substrates and serve to complement cell-based studies. PMID- 26360030 TI - An ACAP1 coat complex acting in endocytic recycling. AB - A key function of coat proteins is the sorting of protein cargoes into intracellular transport pathways. For many years, however, it has been unclear whether this role of coat proteins would apply to pathways of endocytic recycling. This issue has been clarified in recent years through the identification of multiple coat complexes acting in the recycling pathways. Leading this charge have been studies on a coat complex defined by ACAP1 (adenosine diphosphate ribosylation factor GTPase-activating proteins with Coiled coil, Ankryin repeat and PH domains 1), which acts in the sorting of cargoes at the recycling endosome for their return to the plasma membrane. This chapter describes the methods used to characterize this role of ACAP1. PMID- 26360031 TI - Biochemical methods for studying kinetic regulation of Arf1 activation by Sec7. AB - The ADP ribosylation factor (Arf) family of small guanosine triphosphatases (GTPases) regulates vesicular transport at several locations within the cell, and is in turn regulated by guanine nucleotide exchange factors (GEFs) via a conserved catalytic domain, termed the Sec7 domain. The catalytic activity of the Sec7 domain is well characterized in the context of a few GEFs acting at the periphery of the cell. This chapter describes the techniques used to extend the biochemical analysis of activity to the much larger GEFs acting on the Arf family in the core secretory pathway, using the activity of Saccharomyces cerevisiae Sec7 on Arf1, regulating export from the trans-Golgi network, as a model. The complete methods for purification to near homogeneity of all proteins required, including several Sec7 constructs and multiple relevant small GTPases, are detailed. These are followed by methods for the quantification of the nucleotide exchange activity of Sec7 in a physiologically relevant context, including modifications required to dissect the signal integration functions of Sec7 as an effector of several other small GTPases, and methods for identifying stable Sec7 small GTPase interactions in the presence of membranes. These techniques may be extended to the analysis of similar members of the Sec7 GEF subfamily in other species and acting elsewhere in the secretory pathway. PMID- 26360032 TI - Rab and Arf G proteins in endosomal trafficking. AB - Endocytosis is a fundamental process that cells use to remove receptors, extracellular material, plasma membrane proteins and lipids from the cell surface. After entry into cells, the cargo proteins are subsequently trafficked to late endosomes and lysosomes for degradation, to the Golgi complex, or to recycling endosomes for return to the plasma membrane. Small G proteins in the Rab and Arf family are present on endosomes and coordinate the trafficking of cargo proteins. Here we describe some basic experimental approaches to begin to study the endosomal trafficking of a given cell surface protein. PMID- 26360033 TI - Qualitative and quantitative analysis of endocytic recycling. AB - Endocytosis, which encompasses the internalization and sorting of plasma membrane (PM) lipids and proteins to distinct membrane-bound intracellular compartments, is a highly regulated and fundamental cellular process by which eukaryotic cells dynamically regulate their PM composition. Indeed, endocytosis is implicated in crucial cellular processes that include proliferation, migration, and cell division as well as maintenance of tissue homeostasis such as apical-basal polarity. Once PM constituents have been taken up into the cell, either via clathrin-dependent endocytosis (CDE) or clathrin-independent endocytosis (CIE), they typically have two fates: degradation through the late-endosomal/lysosomal pathway or returning to the PM via endocytic recycling pathways. In this review, we will detail experimental procedures that allow for both qualitative and quantitative assessment of endocytic recycling of transmembrane proteins internalized by CDE and CIE, using the HeLa cervical cancer cell line as a model system. PMID- 26360034 TI - Methods for analyzing the role of phospholipase A2 enzymes in endosome membrane tubule formation. AB - Cargo export from mammalian endosomal compartments often involves membrane tubules, into which soluble and membrane-bound cargos are segregated for subsequent intracellular transport. These membrane tubules are highly dynamic and their formation is mediated by a variety of endosome-associated proteins. However, little is known about how these membrane tubules are temporally or spatially regulated, so other tubule-associated proteins are likely to be discovered and analyzed. Therefore, methods to examine the biogenesis and regulation of endosome membrane tubules will prove to be valuable for cell biologists. In this chapter, we describe methods for studying this process using both cell-free, in vitro reconstitution assays, and in vivo image analysis tools. PMID- 26360035 TI - In vivo analysis of recycling endosomes in Caenorhabditis elegans. AB - The microscopic nematode Caenorhabditis elegans (C. elegans) serves as an excellent animal model for studying membrane traffic. This is due in part to its highly advanced genetics and genomics, and a transparent body that allows the visualization of fluorescently tagged molecules in the physiologically relevant context of the intact organism. Notably, C. elegans oocytes, coelomocytes, and intestinal epithelia have been established as facile cellular models to explore nonpolarized and polarized cell membrane trafficking mechanisms. In this chapter, we describe in vivo C. elegans assays, utilizing fluorescent dyes or proteins, to examine the molecular mechanisms that control endocytosis and endocytic recycling. Tissue-specific, steady-state imaging and associated quantitative analysis allow the identification and interpretation of subcellular events in the intact animal. To better understand the kinetic characteristics of recycling tubules that mediate membrane protein recycling, we describe recently developed dynamic-imaging assays in intestinal epithelial cells. Such methods bring new clarity to the system, helping to elucidate the functional roles of recycling mediators. PMID- 26360036 TI - Monitoring receptor trafficking following retromer and WASH deregulation. AB - Cell surface receptors that have been internalized and enter the endocytic pathway have multiple fates including entrance into the multivesicular body pathway on their way to lysosomal degradation, recycling back to the cell surface, or retrograde trafficking out of the endolysosomal system back to the Golgi apparatus. Two ubiquitously expressed protein complexes, WASH and the endosomal coat complex retromer, function together to play a central role in directing the fate of receptors into the latter two pathways. In this chapter, we describe fluorescent- and flow cytometry-based methods for analyzing the recycling and retrograde trafficking of two receptors, alpha5beta1 and CI-M6PR, whose intracellular fates are regulated by WASH and retromer activity. The guidelines presented in this chapter can be applied to the analysis of any cell surface or intracellular membrane protein to determine the impact of WASH or retromer deregulation on its intracellular trafficking route. PMID- 26360037 TI - Quantitative analysis of endosome tubulation and microdomain organization mediated by the WASH complex. AB - Sorting of cargoes in endosomes occurs through their concentration into sorting platforms, called microdomains, from which transport intermediates are formed. The WASH complex localizes to such endosomal microdomains and triggers localized branched actin nucleation by activating the Arp2/3 complex. These branched actin networks are required for both the lateral compartmentalization of endosome membranes into distinct microdomains and for the fission of transport intermediates from these sorting platforms. In this chapter, we provide experimental protocols to study these two aspects of WASH physiology. We first describe how to image the dynamic membrane tubules resulting from the defects of WASH-mediated fission. We then describe how to study quantitatively the microdomain localization of WASH in live and fixed cells. Since microdomains are below the resolution limit of conventional light-microscopy techniques, this required the development of specific image analysis pipelines, which are detailed. The guidelines presented in this chapter can apply to other endomembrane microdomains beyond WASH in order to increase our understanding of trafficking in molecular and quantitative terms. PMID- 26360038 TI - Rab GTPases and kinesin motors in endosomal trafficking. AB - The endocytic pathway is composed of distinct types of endosomes that vary in shape, function, and molecular composition. In addition, endosomes are highly dynamic structures that continuously receive, sort, and deliver molecules to other organelles. Among organizing machineries that contribute to endosomal functions, Rab GTPases and kinesin motors play critical roles. Rab proteins define the identity of endosomal subdomains by recruiting set of effectors among which kinesins shape and transport membranous carriers along the microtubule network. In this review, we provide detailed protocols from live cell imaging to electron microscopy and biochemical approaches to address how Rab and kinesin proteins cooperate molecularly and functionally within the endocytic pathway. PMID- 26360039 TI - Measuring receptor recycling in polarized MDCK cells. AB - Recycling of proteins such as channels, pumps, and receptors is critical for epithelial cell function. In this chapter we present a method to measure receptor recycling in polarized Madin-Darby canine kidney cells using an iodinated ligand. We describe a technique to iodinate transferrin (Tf), we discuss how (125)I-Tf can be used to label a cohort of endocytosed Tf receptor, and then we provide methods to measure the rate of recycling of the (125)I-Tf-receptor complex. We also show how this approach, which is easily adaptable to other proteins, can be used to simultaneously measure the normally small amount of (125)I-Tf transcytosis and degradation. PMID- 26360041 TI - Analyzing the role of AP-1B in polarized sorting from recycling endosomes in epithelial cells. AB - Epithelial cells polarize their plasma membrane into apical and basolateral domains where the apical membrane faces the luminal side of an organ and the basolateral membrane is in contact with neighboring cells and the basement membrane. To maintain this polarity, newly synthesized and internalized cargos must be sorted to their correct target domain. Over the last ten years, recycling endosomes have emerged as an important sorting station at which proteins destined for the apical membrane are segregated from those destined for the basolateral membrane. Essential for basolateral sorting from recycling endosomes is the tissue-specific adaptor complex AP-1B. This chapter describes experimental protocols to analyze the AP-1B function in epithelial cells including the analysis of protein sorting in LLC-PK1 cells lines, immunoprecipitation of cargo proteins after chemical crosslinking to AP-1B, and radioactive pulse-chase experiments in MDCK cells depleted of the AP-1B subunit MU1B. PMID- 26360040 TI - Structural and functional analysis of endosomal compartments in epithelial cells. AB - Epithelial cells display segregated early endosomal compartments, termed apical sorting endosomes and basolateral sorting endosomes, that converge into a common late endosomal-lysosomal degradative compartment and common recycling endosomes (CREs). Unlike recycling endosomes of nonpolarized cells, CREs have the ability to sort apical and basolateral plasma membrane proteins into distinct apical and basolateral recycling routes, utilizing mechanisms similar to those employed by the trans Golgi network in the biosynthetic pathway. The apical recycling route includes an additional compartment, the apical recycling endosomes, consisting of multiple vesicles bundled around the basal body. Recent evidence indicates that, in addition to their role in internalizing ligands and recycling their receptors back to the cell surface, endosomal compartments act as intermediate stations in the biosynthetic routes to the plasma membrane. Here we review methods employed by our laboratory to study the endosomal compartments of epithelial cells and their multiple trafficking roles. PMID- 26360042 TI - Recycling of the insulin-responsive glucose transporter Glut4 regulated by the small GTPase RalA and the exocyst complex. AB - Endocytic recycling represents a major mechanism for continuous supply of molecules to the plasma membrane. Particularly, outbound trafficking of the recycling endosome (RE) or RE-derived vesicles can be upregulated by cellular signaling, through mobilization of specialized protein complexes acting as transport machineries. Therefore, biochemical and functional characterization of cell signaling molecules that operate multimeric protein complexes in membrane transport provides important insights to signaling-regulated trafficking events. In this chapter, we described biochemical approaches and reporter assays in differentiated adipocytes to determine the activity and function of the small GTPase RalA, which relays upstream insulin signaling to the exocyst complex that targets intracellular vesicles bearing the Glut4 transporter to the plasma membrane. The experimental design outlined in this chapter can be applied to other regulated transport events facilitated by the exocyst complex, as well as other GTPases that operate distinct transport complexes in specific physiological settings. PMID- 26360043 TI - GPCR sorting at multivesicular endosomes. AB - The lysosomal degradation of G protein-coupled receptors (GPCRs) is essential for receptor signaling and down regulation. Once internalized, GPCRs are sorted within the endocytic pathway and packaged into intraluminal vesicles (ILVs) that bud inward to form the multivesicular endosome (MVE). The mechanisms that control GPCR sorting and ILV formation are poorly understood. Quantitative strategies are important for evaluating the function of adaptor and scaffold proteins that regulate sorting of GPCRs at MVEs. In this chapter, we outline two strategies for the quantification and visualization of GPCR sorting into the lumen of MVEs. The first protocol utilizes a biochemical approach to assay the sorting of GPCRs in a population of cells, whereas the second strategy examines GPCR sorting in individual cells using immunofluorescence confocal microscopy. Combined, these assays can be used to establish the kinetics of activated GPCR lysosomal trafficking in response to specific ligands, as well as evaluate the contribution of endosomal adaptors to GPCR sorting at MVEs. The protocols presented in this chapter can be adapted to analyze GPCR sorting in a myriad of cell types and tissues, and expanded to analyze the mechanisms that regulate MVE sorting of other cargoes. PMID- 26360044 TI - Visualizing and quantitating sequence-dependent GPCR recycling. AB - Recent advances in direct imaging have given us a new appreciation of the spatial and temporal dynamics of membrane trafficking processes, and have allowed us to ask questions that were difficult to address with traditional methods. A relevant example of this is protein sorting in the endosome, which serves as the primary sorting station for proteins internalized from the cell surface. In this chapter, we discuss fluorescence imaging protocols to directly visualize and quantitate the recycling of G protein-coupled receptors (GPCRs)-a highly physiologically relevant family of signaling receptors-in real time in living cells. The protocols allow direct visualization and quantitation of both GPCR exit from the endosome and GPCR delivery to the cell surface. The methods may be extended to study the endolysosomal sorting of many proteins that undergoes endocytic cycling, and may be adapted to other organelles and systems where proteins are sorted. PMID- 26360045 TI - Methods to study endocytic trafficking of the EGF receptor. AB - Endocytosis and postendocytic sorting of epidermal growth factor (EGF) receptor (EGFR) are the major regulators of EGFR signaling. EGFR endocytosis and ubiquitin dependent lysosomal targeting are also considered to be the prototypic experimental system for studying the molecular mechanisms of stimulus-induced and constitutive endocytic trafficking. Therefore, elucidation of the mechanisms of EGFR endocytosis and its regulation of the signaling network is essential not only for better understanding of the EGFR biology but also for defining general regulatory principles in the endocytosis system. Comprehensive analysis of these mechanisms requires quantitative and physiologically relevant methodological approaches for measuring the rates of EGFR internalization, degradation, and recycling. Basic experimental protocols described in this chapter cover a combination of single-cell microscopy and biochemical methods that are used to follow EGF-induced endocytosis of EGFR in real time, measure the kinetic rate parameters of EGFR internalization and recycling, and analyze EGF-dependent ubiquitination and degradation of EGFR. PMID- 26360046 TI - A Prospective Study Evaluating Metabolic Capacity of Thiopurine and Associated Adverse Reactions in Japanese Patients with Inflammatory Bowel Disease (IBD). AB - Azathioprine (AZA) is frequently used in patients with inflammatory bowel disease (IBD). However, toxic adverse reactions frequently develop and limit the clinical benefits. Currently, the precise mechanisms underlying thiopurine-related toxicity are not well understood. To investigate the relationship between the extent of thiopurine metabolism and adverse reactions in Japanese IBD patients, we prospectively observed 48 IBD patients who received AZA. We analyzed the thiopurine S-methyltransferase (TPMT) and inosine triphosphate pyrophosphatase (ITPA) gene mutations and measured the concentrations of 6-thioguanine nucleotide (6-TGN) continuously for 52 weeks. All patients possessed wild-type TPMT gene sequences. The ITPA 94C>A mutation was detected in 19 patients (39.6%). Adverse reactions developed in 14 of the 48 patients (29.2%), including leukopenia in 10 patients (20.8%). In the leukopenia group, the percentages of patients with 94C>A were higher than those in the without-leukopenia group (70.0% vs. 31.6%, P < 0.05). The average concentrations of 6-TGN in the patients with 94C>A were generally higher than those in the patients without 94C>A, however, there were no significant differences. Only 3 out of 10 patients with leukopenia exhibited high 6-TGN levels (30.0%). No negative correlations between white blood cell (WBC) counts and 6-TGN concentrations were observed. The cumulative incidence of leukopenia were higher for patients with 94C>A. Seven out of 19 patients (36.8%) with the ITPA 94C>A mutation developed leukopenia; however, this mutation may not unequivocally increase the risk of developing leukopenia. In addition, there are factors other than increased 6-TGN levels that are involved in the onset of leukopenia. PMID- 26360048 TI - (2-Arylethenyl)-1,3,5-triazin-2-amines as a novel histamine H4 receptor ligands. AB - Within the constantly growing number of histamine H4 (H4R) receptor ligands there is a large group of azine derivatives. A series of novel compounds in the group of 4-methylpiperazine-1,3,5-triazine-2-amines were designed and obtained. Considered structures were modified at the triazine 6-position by introduction of variously substituted arylethenyl moieties. Their affinities to histamine H4 receptors were evaluated in radioligand binding assays with use of Sf9 cells, transiently expressing human H4R. Pharmacological studies results allowed to identify 4-[(E)-2-(3-chlorophenyl)ethenyl]-6-(4-methylpiperazin-1-yl)-1,3,5 triazin-2-amine (Ki = 253 nM) as the most potent compound in the present series. PMID- 26360047 TI - Wittig derivatization of sesquiterpenoid polygodial leads to cytostatic agents with activity against drug resistant cancer cells and capable of pyrrolylation of primary amines. AB - Many types of cancer, including glioma, melanoma, non-small cell lung cancer (NSCLC), among others, are resistant to proapoptotic stimuli and thus poorly responsive to current therapies based on the induction of apoptosis in cancer cells. The current investigation describes the synthesis and anticancer evaluation of unique C12-Wittig derivatives of polygodial, a sesquiterpenoid dialdehyde isolated from Persicaria hydropiper (L.) Delabre. These compounds were found to undergo an unprecedented pyrrole formation with primary amines in a chemical model system, a reaction that could be relevant in the biological environment and lead to the pyrrolation of lysine residues in the target proteins. The anticancer evaluation of these compounds revealed their promising activity against cancer cells displaying various forms of drug resistance, including resistance to proapoptotic agents. Mechanistic studies indicated that compared to the parent polygodial, which displays fixative general cytotoxic action against human cells, the C12-Wittig derivatives exerted their antiproliferative action mainly through cytostatic effects explaining their activity against apoptosis-resistant cancer cells. The possibility for an intriguing covalent modification of proteins through a novel pyrrole formation reaction, as well as useful activities against drug resistant cancer cells, make the described polygodial-derived chemical scaffold an interesting new chemotype warranting thorough investigation. PMID- 26360049 TI - Use of Occult Blood Detection Cards for Real-Time PCR-Based Diagnosis of Schistosoma Mansoni Infection. AB - BACKGROUND: In Schistosoma mansoni infection, diagnosis and control after treatment mainly rely on parasitological stool investigations which are laborious and have limited sensitivity. PCR methods have shown equal or superior sensitivity but preservation and storage methods limit their use in the field. Therefore, the use of occult blood detection cards (fecal cards) for easy sampling and storage of fecal samples for further PCR testing was evaluated in a pilot study. METHODOLOGY: Stool specimens were collected in a highly endemic area for S. mansoni in Ethiopia and submitted in an investigator-blinded fashion to microscopic examination by Kato-Katz thick smear as well as to real-time PCR using either fresh frozen stool samples or stool smears on fecal cards which have been stored at ambient temperature for up to ten months. PRINCIPAL FINDINGS: Out of 55 stool samples, 35 were positive by microscopy, 33 and 32 were positive by PCR of frozen samples and of fecal card samples, respectively. When microscopy was used as diagnostic "gold standard", the sensitivity of PCR on fresh stool was 94.3% (95%-CI: 86.6; 100) and on fecal cards 91.4% (95%-CI: 82.2; 100). CONCLUSIONS: The use of fecal cards proved to be a simple and useful method for stool collection and prolonged storage prior to PCR based diagnosis of S. mansoni infection. This technique may be a valuable approach for large scale surveillance and post treatment assessments. PMID- 26360050 TI - Metformin Ameliorates Inflammatory Bowel Disease by Suppression of the STAT3 Signaling Pathway and Regulation of the between Th17/Treg Balance. AB - OBJECTIVE: Metformin is used to treat type 2 diabetes. We sought to determine whether metformin reduces inflammation, by regulating p-signal transducer and activator of transcription 3 (STAT3) expression and T-helper 17 (Th17) cell proliferation, in a mouse model of inflammatory bowel disease (IBD). METHODS: IBD mice were administered metformin for 16 days and their tissues were analyzed. AMP activated protein kinase (AMPK), the mammalian target of rapamycin (mTOR), p STAT3 and p-STAT5 in the spleen and lymph nodes were detected using immunohistochemistry and confocal microscopy. Gene expression was determined using quantitative PCR assays, and protein expression levels were measured using western blotting and enzyme-linked immunosorbent assays. Human HT-29 cell proliferation was evaluated using MTT assays. RESULTS: Metformin reduced disease activity index scores and inhibited weight loss. Metformin also decreased the colonic histological score and inflammatory mediators and increased colon lengths increased. Treatment with metformin inhibited the expression of interleukin (IL) 17, p-STAT3, and p-mTOR. In contrast, metformin treatment increased expression levels of p-AMPK and Foxp3. In addition, expression of inflammatory cytokines decreased in a dose-dependent manner in inflamed human HT-29 cells cultured with metformin at various concentrations. CONCLUSIONS: Metformin attenuates IBD severity and reduces inflammation through the inhibition of p-STAT3 and IL-17 expression. Our results have increased our understanding of this chronic inflammatory disease, and support the strategy of using p-STAT3 inhibitors to treat IBD. PMID- 26360052 TI - Patent term extension systems differentiate Japanese and US drug lifecycle management. AB - Drug lifecycle management (LCM) contributes to maximizing drug discovery investment returns. After initial drug approval, additional approvals can be sought for novel indications and formulations to extend product marketability. Patents provide additional barriers to entry and patent term extension systems facilitate extension of these. Several aspects of the US and Japanese patent term extension systems differ. Therefore, we compared both systems using a drug LCM case study to highlight the differences. Our findings indicate that the extension of multiple drug patents on multiple occasions in Japan produces a more complicated range of extended patent protections, compared with the US system. PMID- 26360051 TI - Modelling of compound combination effects and applications to efficacy and toxicity: state-of-the-art, challenges and perspectives. AB - The development of treatments involving combinations of drugs is a promising approach towards combating complex or multifactorial disorders. However, the large number of compound combinations that can be generated, even from small compound collections, means that exhaustive experimental testing is infeasible. The ability to predict the behaviour of compound combinations in biological systems, whittling down the number of combinations to be tested, is therefore crucial. Here, we review the current state-of-the-art in the field of compound combination modelling, with the aim to support the development of approaches that, as we hope, will finally lead to an integration of chemical with systems level biological information for predicting the effect of chemical mixtures. PMID- 26360053 TI - Neuroprotective agents for neonatal hypoxic-ischemic brain injury. AB - Hypoxic-ischemic (H-I) brain injury in newborns is a major cause of morbidity and mortality that claims thousands of lives each year. In this review, we summarize the promising neuroprotective agents tested on animal models and pilot clinical studies of neonatal H-I brain injury according to the different phases of the disease. These agents target various phases of injury including the early phase of excitotoxicity, oxidative stress and apoptosis as well as late-phase inflammatory reaction and neural repair. We analyze the cell survival and cell death pathways modified by these agents in neonatal H-I brain injury. We aim to 'build a bridge' between animal trials of neuroprotective agents and potential candidate treatments for future clinical applications against H-I encephalopathy. PMID- 26360054 TI - A comparison between genetically humanized and chimeric liver humanized mouse models for studies in drug metabolism and toxicity. AB - Mice that have been genetically humanized for proteins involved in drug metabolism and toxicity and mice engrafted with human hepatocytes are emerging and promising in vivo models for an improved prediction of the pharmacokinetic, drug-drug interaction and safety characteristics of compounds in humans. The specific advantages and disadvantages of these models should be carefully considered when using them for studies in drug discovery and development. Here, an overview on the corresponding genetically humanized and chimeric liver humanized mouse models described to date is provided and illustrated with examples of their utility in drug metabolism and toxicity studies. We compare the strength and weaknesses of the two different approaches, give guidance for the selection of the appropriate model for various applications and discuss future trends and perspectives. PMID- 26360055 TI - Challenges and opportunities for non-antibody scaffold drugs. AB - The first candidates from the promising class of small non-antibody protein scaffolds are now moving into clinical development and practice. Challenges remain, and scaffolds will need to be further tailored toward applications where they provide real advantages over established therapeutics to succeed in a rapidly evolving drug development landscape. PMID- 26360056 TI - Age-Associated Differences in MiRNA Signatures Are Restricted to CD45RO Negative T Cells and Are Associated with Changes in the Cellular Composition, Activation and Cellular Ageing. AB - MicroRNAs (miRNAs) have emerged as important players in the regulation of T-cell functionality. However, comprehensive insight into the extent of age-related miRNA changes in T cells is lacking. We established miRNA expression patterns of CD45RO- naive and CD45RO+ memory T-cell subsets isolated from peripheral blood cells from young and elderly individuals. Unsupervised clustering of the miRNA expression data revealed an age-related clustering in the CD45RO- T cells, while CD45RO+ T cells clustered based on expression of CD4 and CD8. Seventeen miRNAs showed an at least 2-fold up- or downregulation in CD45RO- T cells obtained from young as compared to old donors. Validation on the same and independent samples revealed a statistically significant age-related upregulation of miR-21, miR-223 and miR-15a. In a T-cell subset analysis focusing on known age-related phenotypic changes, we showed significantly higher miR-21 and miR-223 levels in CD8+CD45RO CCR7- TEMRA compared to CD45RO-CCR7+ TNAIVE-cells. Moreover, miR-21 but not miR 223 levels were significantly increased in CD45RO-CD31- post-thymic TNAIVE cells as compared to thymic CD45RO-CD31+ TNAIVE cells. Upon activation of CD45RO- TNAIVE cells we observed a significant induction of miR-21 especially in CD4+ T cells, while miR-223 levels significantly decreased only in CD4+ T cells. Besides composition and activation-induced changes, we showed a borderline significant increase in miR-21 levels upon an increasing number of population doublings in CD4+ T-cell clones. Together, our results show that ageing related changes in miRNA expression are dominant in the CD45RO- T-cell compartment. The differential expression patterns can be explained by age related changes in T-cell composition, i.e. accumulation of CD8+ TEMRA and CD4+ post-thymic expanded CD31- T cells and by cellular ageing, as demonstrated in a longitudinal clonal culture model. PMID- 26360057 TI - Rock Climbing Injuries: Acute and Chronic Repetitive Trauma. AB - Rock climbing has increased in popularity as a sport, and specific injuries related to its practice are becoming more common. Chronic repetitive injuries are more common than acute injuries, although acute injuries tend to be more severe. We review both acute and chronic upper and lower extremity injuries. Understanding the injury pattern in rock climbers is important for accurate diagnosis. PMID- 26360058 TI - Phosphoflow-Based Evaluation of Mek Inhibitors as Small-Molecule Therapeutics for B-Cell Precursor Acute Lymphoblastic Leukemia. AB - Upstream mutations that lead to constitutive activation of Erk in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) are relatively common. In the era of personalized medicine, flow cytometry could be used as a rapid method for selection of optimal therapies, which may include drugs that target the Erk pathway. Here, we evaluated the utility of phospho-flow, compared to Western blotting, to monitor Erk pathway activation and its inhibition by targeted Mek kinase inhibitors in human BCP ALL. Because the Erk pathway is not only activated endogenously, by mutations, but also by normal extracellular stimulation through stromal contact and serum growth factors, we compared Erk activation ex vivo in ALL cells in the presence and absence of stroma and serum. Phospho-flow was able to readily detect changes in the pool of pErk1/2 that had been generated by normal microenvironmental stimuli in patient-derived BCP-ALL cells passaged in NSG mice, in viably frozen primary patient samples, and in fresh patient samples. Treatment with the Mek1/2 inhibitor selumetinib resulted in a rapid, complete and persistent reduction of microenvironment-generated pErk1/2. Imaging flow cytometry confirmed reduction of nuclear pErk1/2 upon selumetinib treatment. An ALL relapsing with an activating KRasG12V mutation contained higher endogenous as well as serum/stromal-stimulated levels of pErk1/2 than the matched diagnosis sample which lacked the mutation, but selumetinib treatment reduced pErk1/2 to the same level in both samples. Selumetinib and trametinib as Mek inhibitors were mainly cytostatic, but combined treatment with the PI3K? inhibitor CAL101 increased cytotoxicity. Thus phospho-flow cytometry could be used as a platform for rapid, individualized in vitro drug sensitivity assessment for leukemia patients at the time of diagnosis. PMID- 26360060 TI - Power to you. PMID- 26360059 TI - To Hit or Not to Hit, That Is the Question - Genome-wide Structure-Based Druggability Predictions for Pseudomonas aeruginosa Proteins. AB - Pseudomonas aeruginosa is a Gram-negative bacterium known to cause opportunistic infections in immune-compromised or immunosuppressed individuals that often prove fatal. New drugs to combat this organism are therefore sought after. To this end, we subjected the gene products of predicted perturbative genes to structure-based druggability predictions using DrugPred. Making this approach suitable for large scale predictions required the introduction of new methods for calculation of descriptors, development of a workflow to identify suitable pockets in homologous proteins and establishment of criteria to obtain valid druggability predictions based on homologs. We were able to identify 29 perturbative proteins of P. aeruginosa that may contain druggable pockets, including some of them with no or no drug-like inhibitors deposited in ChEMBL. These proteins form promising novel targets for drug discovery against P. aeruginosa. PMID- 26360061 TI - New treatments for psychotic disorders. PMID- 26360062 TI - Diagnosis of dependence to prescribed pain medication. PMID- 26360063 TI - Voices beyond words. PMID- 26360064 TI - Why collaborative care matters for older adults in China. PMID- 26360065 TI - Being mindful about mindfulness. PMID- 26360067 TI - Corrections. A personal 35 year perspective on Gilles de la Tourette syndrome: prevalence, phenomenology, comorbidities, and coexistent psychopathologies. PMID- 26360066 TI - Psychotherapy provision in the UK: time to think again. PMID- 26360068 TI - Corrections. A personal 35 year perspective on Gilles de la Tourette syndrome: assessment, investigations, and management. PMID- 26360069 TI - The brain disease model of addiction: challenging or reinforcing stigma?- Authors' reply. PMID- 26360070 TI - Heightened risk of false positives in a network meta-analysis of social anxiety. PMID- 26360071 TI - The brain disease model of addiction: challenging or reinforcing stigma? PMID- 26360072 TI - Heightened risk of false positives in a network meta-analysis of social anxiety- Author's reply. PMID- 26360073 TI - Protecting the human rights of people who use psychedelics. PMID- 26360074 TI - Why moving more should be promoted for severe mental illness. PMID- 26360076 TI - Politics on the mind: assessing the state of mental health after the election. PMID- 26360077 TI - Eduard Vieta: unravelling bipolar disorder's mysteries. PMID- 26360078 TI - 36 minutes and 40 seconds. PMID- 26360079 TI - A tough nut to crack. PMID- 26360080 TI - Recovery: a piece of cake. PMID- 26360081 TI - The art of losing. PMID- 26360082 TI - We could be heroes. PMID- 26360083 TI - Effects of cognitive behaviour therapy for worry on persecutory delusions in patients with psychosis (WIT): a parallel, single-blind, randomised controlled trial with a mediation analysis. AB - BACKGROUND: Worry might be a contributory causal factor in the occurrence of persecutory delusions in patients with psychotic disorders. Therefore we postulated that reducing worry with cognitive behaviour therapy (CBT) would reduce persecutory delusions. METHODS: For our two-arm, assessor-blinded, randomised controlled trial (Worry Intervention Trial [WIT]), we recruited patients aged 18-65 years with persistent persecutory delusions but non-affective psychosis from two centres: the Oxford Health National Health Service (NHS) Foundation Trust (Oxford, UK) and the Southern Health NHS Foundation Trust (Southampton, UK). The key inclusion criteria for participants were a score of at least 3 on the Psychotic Symptoms Rating Scale (PSYRATS) denoting a current persecutory delusion; that the delusion had persisted for at least 3 months; a clinical diagnosis of schizophrenia, schizoaffective disorder, or delusional disorder; and a clinically significant level of worry. We randomly assigned (1:1) eligible patients, using a randomly permuted block procedure with variable block sizes and division by four strata, to either six sessions of worry-reduction CBT intervention done over 8 weeks added to standard care (the CBT-intervention group), or to standard care alone (the control group). The assessors were masked to patient allocations and did their assessments at week 0 (baseline), 8 weeks (end of treatment), and 24 weeks, follow-up. The primary outcomes were worry measured by the Penn State Worry Questionnaire (PSWQ) and delusions measured by the PSYRATS-delusion scale; we did the analyses in the intention-to-treat population, and also did a planned mediation analysis. This trial is registered with the ISRCTN Registry (number ISRCTN23197625) and is closed to new participants. FINDINGS: From Nov 1, 2011, to Sept 9, 2013, we recruited 150 eligible participants and randomly assigned 73 to the CBT intervention group, and 77 to the control group. 143 patients (95%) provided primary outcome follow-up data. Compared with standard care alone, at 8 weeks the CBT intervention significantly reduced worry (mean difference 6.35 [SE 1.56] PSWQ units, 95% CI 3.30-9.40; p<0.001) and persecutory delusions (2.08 [SE 0.73] PSYRATS units, 95% CI 0.64-3.51; p=0.005). The reductions were maintained to 24 weeks follow-up. The mediation analysis suggested that the change in worry accounted for 66% of the change in delusion. No patients died or were admitted to secure units during our study. Six suicide attempts (two in the CBT intervention group, and four in the control group) and two serious violent incidents (one in each group) were noted, but no adverse events were deemed related to the treatments or the assessments. INTERPRETATION: To our knowledge, this is the first large trial focused on persecutory delusions. We have shown that long-standing delusions were significantly reduced by a brief intervention targeted on worry, although the limitations for our study include no determination of the key elements within the intervention. Our results suggest that worry might cause paranoia, and that worry intervention techniques might be a beneficial addition to the standard treatment of psychosis. FUNDING: Efficacy and Mechanism Evaluation programme, which is a UK Medical Research Council and National Institute of Health Research partnership. PMID- 26360084 TI - Agreement between definitions of pharmaceutical opioid use disorders and dependence in people taking opioids for chronic non-cancer pain (POINT): a cohort study. AB - BACKGROUND: Classification of patients with pharmaceutical opioid use disorder and dependence varies depending on which definition is used. We compared how WHO's ICD-10 and proposed ICD-11 and the American Psychiatric Association's DSM IV and DSM-5 classified individuals in a community-based sample of Australians with chronic non-cancer pain for which opioids have been prescribed. METHODS: We studied participants in the Pain and Opioid IN Treatment (POINT) cohort, a 2 year prospective cohort study of 1514 people prescribed pharmaceutical opioids for their chronic pain who were recruited in 2012-13 from community-based pharmacies across Australia. After giving patients the Composite International Diagnostic Interview about their opioid use, we assessed which patients would be categorised as having disorders of pharmaceutical opioid use by ICD-10, the draft ICD-11, DSM IV, and DSM-5. We examined agreement between classification systems, and tested the unidimensionality of the syndrome with confirmatory factor analysis. FINDINGS: We included 1422 participants (median time of pain disorder 10 years [IQR 5-20]; median length of strong opioid prescription 4 years [IQR 1.5-10.0]; mean age 58 years). Similar proportions of individuals met lifetime criteria for dependence with DSM-IV (127; 8.9%), ICD-10 (121; 8.5%), and ICD-11 (141; 9.9%). Criteria in DSM-5 classified 127 (8.9%) participants with moderate or severe use disorder. There was excellent agreement between ICD-10, ICD-11 and DSM-IV dependence (kappa>0.90). However, there was only fair to moderate agreement between ICD-10 and DSM-IV dependence diagnoses, and DSM-5 use disorder (mild, moderate, or severe). There was only good agreement between moderate to severe use disorder in DSM-5 and the other definitions. Criteria for all definitions loaded well on a single factor; the best model fit was for the definition for dependence in the draft ICD-11, the worst was in DSM-5. INTERPRETATION: Classification of problematic pharmaceutical opioid use varies across editions of ICD and DSM. The much lower levels of agreement between DSM-5 and other definitions than between other definitions might be attributed to DSM-5 containing an increased number of criteria and treating dependence and problematic use as a continuum. The more parsimonious ICD-11 dependence definition showed excellent model fit and excellent agreement with previous classificatory systems. FUNDING: Australian National Health and Medical Research Council. PMID- 26360085 TI - Experiences of hearing voices: analysis of a novel phenomenological survey. AB - BACKGROUND: Auditory hallucinations--or voices--are a common feature of many psychiatric disorders and are also experienced by individuals with no psychiatric history. Understanding of the variation in subjective experiences of hallucination is central to psychiatry, yet systematic empirical research on the phenomenology of auditory hallucinations remains scarce. We aimed to record a detailed and diverse collection of experiences, in the words of the people who hear voices themselves. METHODS: We made a 13 item questionnaire available online for 3 months. To elicit phenomenologically rich data, we designed a combination of open-ended and closed-ended questions, which drew on service-user perspectives and approaches from phenomenological psychiatry, psychology, and medical humanities. We invited people aged 16-84 years with experience of voice-hearing to take part via an advertisement circulated through clinical networks, hearing voices groups, and other mental health forums. We combined qualitative and quantitative methods, and used inductive thematic analysis to code the data and chi(2) tests to test additional associations of selected codes. FINDINGS: Between Sept 9 and Nov 29, 2013, 153 participants completed the study. Most participants described hearing multiple voices (124 [81%] of 153 individuals) with characterful qualities (106 [69%] individuals). Less than half of the participants reported hearing literally auditory voices--70 (46%) individuals reported either thought-like or mixed experiences. 101 (66%) participants reported bodily sensations while they heard voices, and these sensations were significantly associated with experiences of abusive or violent voices (p=0.024). Although fear, anxiety, depression, and stress were often associated with voices, 48 (31%) participants reported positive emotions and 49 (32%) reported neutral emotions. Our statistical analysis showed that mixed voices were more likely to have changed over time (p=0.030), be internally located (p=0.010), and be conversational in nature (p=0.010). INTERPRETATION: This study is, to our knowledge, the largest mixed-methods investigation of auditory hallucination phenomenology so far. Our survey was completed by a diverse sample of people who hear voices with various diagnoses and clinical histories. Our findings both overlap with past large-sample investigations of auditory hallucination and suggest potentially important new findings about the association between acoustic perception and thought, somatic and multisensorial features of auditory hallucinations, and the link between auditory hallucinations and characterological entities. FUNDING: Wellcome Trust. PMID- 26360086 TI - Depression care management for adults older than 60 years in primary care clinics in urban China: a cluster-randomised trial. AB - BACKGROUND: China's national health policy classifies depression as a chronic disease that should be managed in primary care settings. In some high-income countries use of chronic disease management principles and primary care-based collaborative-care models have improved outcomes for late-life depression; however, this approach has not yet been tested in China. We aimed to assess whether use of a collaborative-care depression care management (DCM) intervention could improve outcomes for Chinese adults with depression aged 60 years and older. METHODS: Between Jan 17, 2011, [corrected] and Nov 30, 2013, we did a cluster-randomised trial in patients from primary care centre clinics in Shangcheng district of Hangzhou city in eastern China. We randomly assigned (1:1) clinics to either DCM (involving training for physicians in use of treatment guidelines, training for primary care nurses to function as care managers, and consultation with psychiatrists as support) or to give enhanced care as usual to all eligible patients aged 60 years and older with major depressive disorder. Clinics were chosen randomly for inclusion from all primary care clinics in the district by computer algorithm and then randomly allocated depression care interventions remotely by computer algorithm. Physicians, study personnel, and patients were not masked to clinic assignment. Our primary outcome was difference in Hamilton Depression Rating Scale (HAMD) score using data for clusters at baseline and 3, 6, and 12 month follow-up in a mixed-effects model of the intention-to-treat population. We originally aimed to analyse outcomes at 24 months, however the difference between groups at 12 months was large and funding was insufficient to continue to 24 months, therefore we decided to end the trial at 12 months. This trial is registered with ClinicalTrials.gov, number NCT01287494. FINDINGS: Of 34 primary care clinics in Shangcheng district, 16 were randomly chosen. We randomly assigned eight clinics to the DCM intervention (164 patients enrolled) and eight primary care clinics to enhanced care as usual (162 patients). There were no major differences in baseline demographic and clinical variables between the groups of patients for each intervention. Over the 12 months, patients in clinics assigned to DCM had a significantly greater reduction in HAMD score than did those in practices assigned to enhanced care as usual (estimated between group difference -6.5 [95% CI -7.1 to -5.9]; Cohen's d 0.8 [95% CI 0.8-0.9]; p<0.0001). The intercluster correlation for change in HAMD total score was 0.07 (95% CI 0.06-0.08). There were no study-related adverse events in either group. INTERPRETATION: Clinical outcomes of Chinese adults older than 60 years who had major depression were improved when their primary care clinic used DCM. Primary care-based collaborative management of depression is promising to address this pressing public health need in China. FUNDING: National Institutes of Health, Program for New Century Excellent Talents in Universities of China, Ministry of Education, China. PMID- 26360087 TI - New perspectives on schizophrenia in later life: implications for treatment, policy, and research. AB - Worldwide, in the past few decades, the demographics of older people (ie, people 55 years and over) with schizophrenia have changed completely with respect to absolute numbers of people affected, the proportion of all people with the disorder, life expectancy, and residential status. The ageing schizophrenia population has created vast health-care needs and their medical comorbidity contributes to higher mortality than in the general population. Proposals to classify schizophrenia into early-onset, late-onset, and very-late-onset subtypes now should be tempered by the recognition that comorbid medical and neurological disorders can contribute to psychotic symptoms in later life. The concept of outcome has become more nuanced with an appreciation that various outcomes can occur, largely independent of each other, that need different treatment approaches. Data show that schizophrenia in later life is not a stable end-state but one of fluctuation in symptoms and level of functioning, and show that pathways to improvement and recovery exist. Several novel non-pharmacological treatment strategies have been devised that can augment the clinical options used to address the specific needs of older adults with schizophrenia. PMID- 26360088 TI - Targeting the biased brain: non-invasive brain stimulation to ameliorate cognitive control. AB - Non-invasive brain stimulation has become important for the investigation of healthy and impaired neuronal functioning. Moreover, non-invasive brain stimulation has emerged as a new means of psychiatric treatment, although the mechanisms of action are still not understood and the optimal mode of application is still under development. Dysfunctional cognitive control is a central characteristic of various psychiatric disorders and is associated with dysregulations of prefrontal cortex activity and biased information processing. With non-invasive brain stimulation, enhancement and reduction of prefrontal cortex activity were shown to ameliorate and impair cognitive control, respectively. These findings suggest a neurocognitive mechanism of therapeutic effects and that non-invasive brain stimulation can be combined with training to target dysfunctional cognitive control and related clinical symptomatology. Nevertheless, the intra-individual and inter-individual diversity of neurocognitive processes, the multiplicity of possible stimulation parameters, and the complexity of interactions between those factors pose considerable challenges for interpretation of these findings and their clinical application. PMID- 26360089 TI - Pharmacological cognitive enhancement: treatment of neuropsychiatric disorders and lifestyle use by healthy people. AB - Neuropsychiatric disorders typically manifest as problems with attentional biases, aberrant learning, dysfunctional reward systems, and an absence of top down cognitive control by the prefrontal cortex. In view of the cost of common mental health disorders, in terms of distress to the individual and family in addition to the financial cost to society and governments, new developments for treatments that address cognitive dysfunction should be a priority so that all members of society can flourish. Cognitive enhancing drugs, such as cholinesterase inhibitors and methylphenidate, are used as treatments for the cognitive symptoms of Alzheimer's disease and attention deficit hyperactivity disorder. However, these drugs and others, including modafinil, are being increasingly used by healthy people for enhancement purposes. Importantly for ethical and safety reasons, the drivers for this increasing lifestyle use of so called smart drugs by healthy people should be considered and discussions must occur about how to ensure present and future pharmacological cognitive enhancers are used for the benefit of society. PMID- 26360090 TI - Methods and outcome reporting in the PACE trial. PMID- 26360091 TI - Methods and outcome reporting in the PACE trial--Author's reply. PMID- 26360092 TI - Northern lights. PMID- 26360093 TI - We are the robots. PMID- 26360094 TI - Psychotherapy: beware of false certitude. PMID- 26360095 TI - Mental health: moving beyond remission of symptoms. PMID- 26360096 TI - Omission of data weakens the case for causal mediation in the PACE Trial. PMID- 26360097 TI - In non-blinded trials, self-report measures could mislead. PMID- 26360098 TI - Post-exertional malaise in chronic fatigue syndrome. PMID- 26360099 TI - Doubts over the validity of the PACE hypothesis. PMID- 26360100 TI - In vitro antitumor activity of free and nano-encapsulated Na5[PMo10V2O40].nH2O and its binding properties with ctDNA by using combined spectroscopic methods. AB - Free and nanosized starch and lipid encapsulated Na5[PMo10V2O40].nH2O complexes (abbreviated as PMoV, SEP and LEP, respectively) have been prepared and structurally characterized by Fourier transform infrared (FT-IR) spectroscopy, inductively coupled plasma (ICP) analysis, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images. The results show that the PMoV retains its parent structure after encapsulation by starch and lipid nanoparticles. The in vitro antitumor activity of PMoV in its free and nano encapsulated forms was investigated using the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl-tetrazolium bromide (MTT) assay that was carried out on two types of human cancer cells, MCF-7 (breast cancer cells) and HEK-293 (Human Embryonic Kidney). The results represent the enhancement of cell penetration and antitumor activity of PMoV due to its encapsulation in starch or lipid nanoparticles. However, this observed enhancement for the lipid relative to the starch nanocapsule can be attributed to its smaller size. In order to investigate the molecular nature of antitumor activity, the binding properties of PMoV with calf thymus DNA (ctDNA) were also comprehensively evaluated using UV-vis absorption spectroscopy, fluorescence quenching and fluorescence Scatchard plots. The results rule out the intercalating binding mode and propose the groove or outside stacking binding for PMoV. However, a biphasic binding behavior that is due to the change in the binding mode was observed by varying of [PMoV]/[ctDNA] mole ratio. The results of cell culture assay and DNA binding experiments represent that the rate of cell penetration is more important than DNA binding affinity in the antitumor activity for POM. PMID- 26360101 TI - Catalytic activity for oxygen reduction reaction on platinum-based core-shell nanoparticles: all-electron density functional theory. AB - Pt nanoparticles (NPs) in a proton exchange membrane fuel cell as a catalyst for an oxygen reduction reaction (ORR) fairly overbind oxygen and/or hydroxyl to their surfaces, causing a large overpotential and thus low catalytic activity. Realizing Pt-based core-shell NPs (CSNPs) is perhaps a workaround for the weak binding of oxygen and/or hydroxyl without a shortage of sufficient oxygen molecule dissociation on the surface. Towards the end, we theoretically examined the catalytic activity of NPs using density functional theory; each NP consists of one of 12 different 3d-5d transition metal cores (groups 8-11) and a Pt shell. The calculation results evidently suggest the enhancement of catalytic activity of CSNPs in particular when 3d transition metal cores are in use. The revealed trends in activity change upon the core metal were discussed with respect to the thermodynamic and electronic structural aspects of the NPs in comparison with the general d-band model. The disparity between the CSNP and the corresponding bilayer catalyst, which is the so-called size effect, was remarkable; therefore, it perhaps opens up the possibility of size-determined catalytic activity. Finally, the overpotential for all CSNPs was evaluated in an attempt to choose promising combinations of CSNP materials. PMID- 26360102 TI - A metal carbonyl-protein needle composite designed for intracellular CO delivery to modulate NF-kappaB activity. AB - Carbon monoxide (CO) has been recognized as a messenger for signal transduction in living cells and tissues. For intracellular CO delivery, several metal carbonyl complexes have been used as CO-releasing molecules (CO-RMs). To improve the properties of CO-RMs, such as the stability and the CO release rate, ligands and carriers of the metal complexes have been exploited. Here we report the development of an efficient intracellular CO delivery system using a protein scaffold. We used a protein needle reconstructed from gene product 5 of bacteriophage T4, which has high cellular permeability and stability. When ruthenium carbonyl complexes are conjugated to the needle using a His-tag triad at the C-terminus, the resulting composite has a significantly higher cellular uptake efficiency of Ru carbonyl and a 12-fold prolonged CO release rate relative to Ru(CO)3Cl(glycinate), a widely used CO-RM. We demonstrate that CO delivered by the composite activates the transcriptional factor nuclear factor-kappaB (NF kappaB), which in turn leads to significant induction of expression of its target genes, HO1, NQO1, and IL6, through generation of reactive oxygen species (ROS). The signaling pathway is distinct from that of tumor necrosis factor (TNF)-alpha induced activation of NF-kappaB. The protein needle-based CO-RM can be exploited to elucidate the biological functions of CO and used in the development of protein-based organometallic tools for modulation of cellular signaling. PMID- 26360103 TI - Synthesis of cyclic diborenes with unprecedented cis-configuration. AB - The first examples of cis-configured diborenes - and the first cyclic diborenes - are isolated by taking advantage of stabilisation by chelating diphosphine ligands. The diborenes are prepared by a convenient one-pot reductive procedure that circumvents the need for a pre-formed base-adduct of the boron-containing precursor. PMID- 26360105 TI - Availability of TNM Staging Data Elements in the Medical Record and Training Needs Assessment: Results from the 2014 SEER Training Needs Assessment for TNM Study. AB - BACKGROUND: In 2016, the cancer registry community will directly assign T, N and M components of stage. The Surveillance, Epidemiology, and End Results program implemented a field study to determine how often T, N and M were not available in the medical record, requiring the registrar to directly assign clinical or pathologic TNM stage components. The field study also identified specific training needs. METHODS: T, N and M status were collected from multiple sources within medical records for a total of 280 cases, 56 each from breast, prostate, colon, lung, and ovarian cancer. TNM data elements were also directly assigned by a series of reviewers and by study participants using the medical records with TNM information redacted. Availability of physician-assigned TNM was estimated from the medical record. Also, participant responses were compared to preferred answers. RESULTS: Pathologic T, N and M were available more often in the medical records than were clinical values and varied by site. Pathologic T and N were available for about two-thirds of the cases, but the clinical elements were available for only about 20% of cases. The agreement between participant responses and review panel assignments varied by data element and cancer site. Agreement was modest for most data elements and cancer sites, ranging from 54% for clinical T to 92% for clinical M for all cancer sites combined. CONCLUSIONS: The data elements for TNM staging and stage group were often missing from the medical records, so registrars in the field will need to assign TNM frequently. Furthermore, the results of this study strongly suggest that more training is required, even among those who currently assign TNM. PMID- 26360104 TI - Association between vitamin C intake and the risk of pancreatic cancer: a meta analysis of observational studies. AB - Quantification of the association between the intake of vitamin C and risk of pancreatic cancer is still conflicting. We therefore conducted a meta-analysis to assess the association between them. Pertinent studies were identified by a search of PubMed and Web of Knowledge throughSeptember of 2014. A random effects model was used to combine the data for analysis. Sensitivity analysis and publication bias were conducted. Data from 17 studies including 4827 pancreatic cancer cases were used in this meta-analysis. Pooled results suggested that highest vitamin C intake amount versus lowest amount was significantlyassociated with reduced the risk of pancreatic cancer [summary relative risk (RR) = 0.705, 95% CI = 0.612-0.811, I(2) = 42.3%]. The associations were also significant both in Caucasian [summary RR = 0.741, 95% CI = 0.626-0.876], Asian [summary RR = 0.455, 95% CI = 0.275-0.754] and Mixed population [summary RR = 0.677, 95% CI = 0.508-0.901]. No publication bias was found. Our analysis suggested that the higher intake of vitamin C might reduce the risk of pancreatic cancer. PMID- 26360106 TI - Evaluating Difficult Decisions in Public Health Surveillance: Striking the Right Balance between Timeliness and Completeness. AB - INTRODUCTION: State-based surveillance programs play a key role in birth defects planning, prevention, education, support, and research activities. High-quality data are essential to all of these functions, and a key indicator of quality is timeliness. The Florida Birth Defects Registry (FBDR)-one of the largest population-based state registries in the United States-faces challenges with timeliness, as evidenced by its 18-month lag time. The goal of this study was to determine if the timeliness of the FBDR could be improved without significantly reducing the completeness of birth defect ascertainment. METHODS: Using 2006-2011 data from the FBDR, we first investigated the timing of diagnosis of birth defects by estimating the effect of different periods of follow-up on prevalence rates reported by the FBDR. We achieved this through retrospective reconstructions of the FBDR under 5 different scenarios with progressively narrower follow-up windows for each infant, and by comparing recalculated rates to the rate of the current FBDR with 1 year of follow-up. We then considered scenarios in which the time lag used to construct the FBDR was reduced (15, 12, 9, and 6 months) by using less data (from 7 to 4 quarters). Recalculated rates were again compared to the current FBDR constructed with 2 years of data and an 18-month lag. Analyses were performed overall and for 44 specific defects. RESULTS: During the 6-year study period, the FBDR identified more than 27,000 infants with a defect detected during the first year of life. Restricting follow up from 1 year to 9 months would only result in a loss of 1.4% of cases. Cutting follow-up in half to 6 months would miss 3.2% of cases, although there was significant variation across defects. Improving timeliness had a small impact on completeness of ascertainment. Overall, compiling the FBDR with only 6 quarters of Florida Agency for Health Care Administration data (as opposed to 8 quarters) would improve timeliness by approximately 6 months, resulting in a registry that is 99.4% complete. DISCUSSION: Six-to-nine month improvements in timeliness were achievable with a minimal sacrifice in completeness (0.6%-1.7%). Efforts to enhance data quality through the assessment of timeliness and completeness indicators are not unique to birth defects surveillance programs. Other programs, particularly those with similar passive case ascertainment protocols, can use our findings to consider a more timely release of registry data, or to design similar investigations of their own. PMID- 26360107 TI - Renal Cancer Patients with Unknown Ethnicity in Cancer Registry Data: Comparisons to Patients with Known Ethnicity. AB - BACKGROUND: Information on ethnicity is important for health disparity research and health service planning. However, information on ethnicity is often incomplete in large routine databases such as cancer registries. This study aimed to compare survival status and other characteristics between cancer patients with and without information on Hispanic ethnicity in cancer registry data. METHODS: The study included 2,426 patients with clear cell renal cell carcinoma (RCC) diagnosed between 1988 and 2004 and identified from the US Department of Defense (DoD)'s Automated Central Tumor Registry (ACTUR) database. There were 1,353 non Hispanic patients, 134 Hispanic patients, and 939 patients with unknown ethnicity. Patients were followed through death, date of last contact, or censored on December 31, 2007. RESULTS: Patients with unknown ethnicity exhibited significantly shorter survival than non-Hispanic or Hispanic patients (Log Rank P < .0001). Further analysis showed that compared to patients with known ethnicity, patients with unknown ethnicity were more likely to have advanced tumor stage at diagnosis and more likely to have missing information on tumor grade, size, and some demographic characteristics. After adjustment for demographic, tumor and treatment variables, patients with unknown ethnicity still exhibited significantly higher mortality than non-Hispanic patients (hazard ratio [HR], 1.69; 95% CI, 1.48-1.92), while Hispanic patients were not different from non Hispanic patients (HR, 0.95; 95% CI, 0.71-1.28). The shorter survival in the unknown ethnicity group was consistently observed in subgroups by age, race, stage, grade, and surgical treatment, suggesting factors other than those investigated in the current study may play a role in the survival differences between patients with and without information on Hispanic ethnicity. IMPLICATIONS: The poor survival of patients with unknown ethnicity in ACTUR warrants further research to elucidate missing mechanisms. Improvement in collection of data by reaching out for more engagement of patients, clinicians and registrars and increasing patient-provider interactions is needed. PMID- 26360108 TI - How the Wisconsin Cancer Reporting System's Data Quality Task Force Started a Cancer Information Management Education Program to Improve Certified Tumor Registrar Recruitment in Wisconsin. AB - The role of the cancer registrar is essential in the effort to gather essential information on most types of cancer diagnosed or treated within a health care institution or within a defined population. These data are used to inform a variety of public health decisions and provide information for cancer diagnosis, treatment, and prevention programs. Effective January 1, 2015, all abstraction of medical records for cancer cases at Commission on Cancer (CoC)-accredited facilities must be performed by cancer registrars who have achieved the Certified Tumor Registrar (CTR) credential. There is a national shortage of CTRs; the National Cancer Registrars Association (NCRA) registration directory, accessed in January 2013, listed just 70 CTRs for Wisconsin. Based on the average annual number of over 29,000 invasive, consolidated cancer cases in Wisconsin (diagnosed in 2006-2010), the average number of cases per CTR was 415, while the US average was 328 cases per CTR. Using this workload estimate, in comparison with other states, Wisconsin was burdened with the sixth highest caseload per CTR in the United States and the highest in the Midwest. Further, there were only 6 Wisconsin candidates for the NCRA CTR-certification exam in 2013. PMID- 26360109 TI - The Good, the Bad, the Ugly...and the Even Better of Rapid Abstracting. AB - With the ever increasing and welcome demand for our cancer registry data at Moffitt Cancer Center (an National Cancer Institute-designated Comprehensive Cancer Center), the traditional cancer registry model of abstracting 4 to 6 months after date of first contact became more and more of a hindrance to the mutual goals and vision for use of our data. We set a goal of utilizing the American College of Surgeon's Rapid Quality Reporting System and we knew that, to use the functionality of that system to improve patient timelines for treatment, we would need to rapidly abstract all our analytic breast and colorectal cases. Rapid abstracting is the method whereby all diagnostic, surgical, and staging information must be gathered in order to complete the first half of the abstract 4 to 6 weeks from date of first contact. PMID- 26360110 TI - Ultra-High-Response, Multiply Twisted Electro-optic Chromophores: Influence of pi System Elongation and Interplanar Torsion on Hyperpolarizability. AB - The systematic synthesis, structural, optical spectroscopic, and second-order nonlinear optical (NLO) characterization of a series of donor-acceptor poly arylene chromophores which have heretofore unachieved pi-extension and substantial twisting from planarity, are reported: specifically, two-ring 2TTMC, dicyano(4-(3,5-dimethyl-1-(2-propylheptyl)pyridin-1-ium-4-yl)-3 methylphenyl)methanide; three-ring 3TTMC, dicyano(4'-(3,5-dimethyl-1-(2 propylheptyl)pyridin-1-ium-4-yl)-2,2',3',5',6'-pentamethyl[1,1'-biphenyl]-4 yl)methanide; and four-ring 4TTMC, dicyano(4"-(3,5-dimethyl-1-(2 propylheptyl)pyridin-1-ium-4-yl)-2,2',3",6,6'-pentamethyl[1,1':4',1"-terphenyl]-4 yl)methanide. Single-crystal X-ray diffraction, DFT-optimized geometries, and B3LYP/INDO-SOS analysis identify three key features underlying the very large NLO response: (1) For ring catenation of three or greater, sterically enforced pi system twists are only essential near the chromophore donor and acceptor sites to ensure large NLO responses. (2) For synthetic efficiency, deletion of one ortho methyl group from o,o',o",o'''-tetramethylbiaryl junctures, only slightly relaxes the biaryl twist angle from 89.6 degrees to ~80 degrees . (3) Increased arylene catenation from two to three to four rings (2TTMC-> 3TTMC -> 4TTMC) greatly enhances NLO response, zwitterionic charge localization, and thus the ground state dipole moment, consistent with the contracted antiparallel solid-state pi pi stacking distances of 8.665 -> 7.883 -> 7.361 A, respectively. This supports zwitterionic ground states in these chromophores as do significant optical spectroscopic solvatochromic shifts, with aryl-aryl twisting turning on significant intra-subfragment absorption. Computed molecular hyperpolarizabilities (MUbeta) approach an unprecedented 900,000 * 10(-48) esu, while estimated chromophore figures of merit, MUbeta(vec)/M(w), approach 1500 * 10(-48) esu, 1.5 times larger than the highest known values for twisted chromophores and >33 times larger than that of planar donor-acceptor chromophores. PMID- 26360111 TI - Numerical analysis of the relationship between the area of target tissue necrosis and the size of target tissue in liver tumours with pulsed radiofrequency ablation. AB - PURPOSE: Radiofrequency ablation (RFA) is currently restricted to the treatment of target tissues with a small size (<3 cm in diameter). To overcome this problem with RFA, some phenomena need to be understood first. The study presented in this paper investigated the relationship between the area of target tissue necrosis (TTN) and the size of target tissue in pulsed radiofrequency ablation (PRFA). MATERIALS AND METHODS: Liver tumour, one of the common targets of RFA in clinical practice, was used as the target tissue in this study. Two types of pulsed RF power supply methods (half-square and half-sine) and three target tissues with different sizes (25 mm, 30 mm and 35 mm in diameter) were studied using finite element modelling. The finite element model (FEM) was validated by using an in vitro experiment with porcine liver tissue. The first roll-off occurrence or 720 s, whichever occurs first, was chosen as the ablation termination criterion in this study. RESULTS: For each target tissue size, the largest TTN area was obtained using the maximum voltage applied (MVA) without roll-off occurrence. In this study, target tissues with a 25 mm diameter can be ablated cleanly but target tissues with 30-mm and 35-mm failed to be ablated. CONCLUSIONS: The half square PRFA could achieve a larger TTN area than the half-sine PRFA. The MVA decreases with an increase in the target tissue diameter in both the half-square PRFA and the half-sine PRFA. The findings of this study are in agreement with the clinical results that lesions (>= 3 cm in diameter) have less favourable results from RFA. PMID- 26360113 TI - Editorial: Sequential giants and the dawn of pediatric neurosurgery. PMID- 26360114 TI - Study of the inflammatory response of immunocytes to polymerized porcine hemoglobin (pPolyHb). AB - Polymerized porcine hemoglobin (pPolyHb), which was synthesized from chemically modified porcine hemoglobin, can carry and deliver oxygen to tissues in addition to restoring intravascular volume. Assessment of the inflammatory response generated in the host is a part of the overall safety evaluation of pPolyHb. In this study, we measured the levels of IL-1beta, IL-10, and CD11b/CD18 in response to pPolyHb stimulation, both in vivo (in rats) and in vitro. Our results suggest that the levels of these indicators are not statistically changed by pPolyHb, indicating that pPolyHb is not immunotoxic to cells and animals in this respect. PMID- 26360112 TI - Chemical Proteomic Platform To Identify Citrullinated Proteins. AB - Anti-citrullinated protein antibodies (ACPAs) are a hallmark of rheumatoid arthritis (RA) and are routinely used for disease diagnosis. Protein citrullination is also increased in cancer and other autoimmune disorders, suggesting that citrullinated proteins may serve as biomarkers for diseases beyond RA. To identify these citrullinated proteins, we developed biotin conjugated phenylglyoxal (biotin-PG). Using this probe and our platform technology, we identified >50 intracellular citrullinated proteins. More than 20 of these are involved in RNA splicing, suggesting, for the first time, that citrullination modulates RNA biology. Overall, this chemical proteomic platform will play a key role in furthering our understanding of protein citrullination in rheumatoid arthritis and potentially a wider spectrum of inflammatory diseases. PMID- 26360115 TI - Prognostic and predictive biomarkers for targeted therapy in NSCLC: for whom the bell tolls? AB - INTRODUCTION: The discovery of molecular biomarkers and the advent of targeted therapies have led to a radical change in the treatment of several tumors, including NSCLC. In the last few years, the number of molecular biomarkers has rapidly increased, and a growing interest has been recently focused on their potential prognostic and predictive value in clinical settings. AREAS COVERED: This review describes all the molecular biomarkers with prognostic and predictive value in NSCLC, including both clinically approved biomarkers, and emerging biomarkers under investigation in clinical trials. Liquid biopsy and applications of circulating biomarkers are also described. EXPERT OPINION: The oncological research is currently focusing on the discovery and validation of molecular biomarkers in order to promote even more personalized treatment strategies. This paradigm of care will expand quickly thanks to the advent of new genotyping technologies, such as next-generation sequencing, making it possible to create a molecular-genomic profile of every patient's tumor. Liquid biopsy and the use of circulating-biomarkers represent the new challenge of oncological research, with very promising implications in the management of patients. PMID- 26360116 TI - Whole Blood PCR Amplification with Pfu DNA Polymerase and Its Application in Single-Nucleotide Polymorphism Analysis. AB - AIMS: Point-of-care genetic analysis may require polymerase chain reaction (PCR) to be carried out on whole blood. However, human blood contains natural inhibitors of PCR such as hemoglobin, immunoglobulin G, lactoferrin, and proteases, as well as anticoagulant agents, including EDTA and heparin that can reduce whole blood PCR efficiency. Our purpose was to develop a highly specific, direct whole blood single-nucleotide polymorphism (SNP) analysis method based on allele-specific (AS) PCR that is mediated by Pfu DNA polymerase and phosphorothioate-modified AS primers. RESULTS: At high Mg(2+) concentrations, Pfu DNA polymerase efficiently amplified genomic DNA in a reaction solution containing up to 14% whole blood. Among the three anticoagulants tested, Pfu DNA polymerase showed the highest activity with sodium citrate. Meanwhile, Triton X 100 and betaine inhibited Pfu DNA polymerase activity in whole blood PCR, whereas trehalose had virtually no effect. These findings provided for the development of a low-cost, simple, and fast direct whole blood genotyping method that uses Pfu DNA polymerase combined with phosphorothioate AS primers for CYP2C9*3 and VKORC1( 1639) loci. CONCLUSIONS: With its high DNA amplification efficiency and tolerance of various blood conditions, Pfu DNA polymerase can be used in clinical laboratories to analyze SNPs in whole blood samples. PMID- 26360117 TI - Comment on "influence of microwaves on the water surface tension". PMID- 26360118 TI - Complete mitochondrial genome of the Himalayan honey bee, Apis laboriosa. AB - The complete mitochondrial genome of Himalayan bee Apis laboriosa, from Mizoram, India, has been sequenced using Illumina NextSeq500 platform and analysed. The mitogenome was assembled and found to be 15 266 bp in length and the gene arrangement is similar to other honey bee species. The A. laboriosa mitogenome comprises of 13 protein-coding genes (PCGs), 22 tRNAs, 2 rRNAs and an A + T-rich region of 346 bp. Based on the concatenated PCGs, in the phylogenetic tree, A. laboriosa is placed as a sister group along with the cavity nesting honey bees. The present study reports the first complete mitochondrial genome sequence of A. laboriosa, which will enhance our knowledge on Apinae mitogenomes and phylogeny. PMID- 26360119 TI - Diagnosing secondary hypogonadism: important consequences for fertility and reversibility. PMID- 26360120 TI - How Like Perceives Like: Gay People on "Gaydar". AB - When lacking explicit knowledge of someone's sexual orientation, gay people commonly assess the likelihood that another is gay using their "gaydar." The term gaydar is a playful mix of the word gay with radar, suggesting that one can sense, intuit, or perceive some set of characteristics in another that signal a shared minority status. While commonly mentioned, the exact criteria a gay person uses when employing their gaydar are little discussed. Drawing methodologically on a series of five focus groups of self-identified lesbians and gay men, this study explores the physical, visual, energetic, and conversational cues gay people consider when they employ the trope of gaydar. Specifically, interview subjects most often described their gaydar as triggered by the following elements: physical presentation, including mannerisms, dress, and voice; interactions, especially eye contact; a presence or absence of certain conversational social norms; and, intangibly, as a kind of energetic exchange. PMID- 26360121 TI - The importance of age groups in estimates of alcohol-attributable mortality: impact on trends in Switzerland between 1997 and 2011. AB - BACKGROUND AND AIMS: Monitoring trends of alcohol-attributable mortality is an integral part of the global strategy to reduce the harmful use of alcohol. However, mortality estimates based on different age ranges come to different conclusions. This study examined the impact of including different age ranges in terms of directions of trends of alcohol-attributable mortality during 14 years in Switzerland. METHOD: Alcohol-attributable mortality was estimated at four time points between 1997 and 2011 using the Global Burden of Disease 2010 methodology. Estimates were obtained for two age groups: 15-64 years and the total adult population (15 years and older). RESULTS: Alcohol-attributable mortality among 15 64-year-olds decreased [1997: 1334 deaths, confidence interval (CI) = 1237-1432; 2011: 1019 deaths, CI = 964-1073; trend per year odds ratio (OR) = 0.99, P < 0.001]. In contrast, alcohol-attributable mortality among those 65 and older increased in the same time-period (1997: 581 deaths, CI = -196 to 1357; 2011: 1664 deaths, CI = 957-2372; OR = 1.07, P< 0.001), resulting in an overall increase of alcohol-attributable mortality for 15+ year-olds (1997: 1915 deaths, CI = 1133-2697; 2011: 2683, CI = 1973-3393; OR = 1.02, P < 0.001). The main shift in trends was due to changes in the mixture (e.g. hypertension, ischaemic heart disease) of cardiovascular diseases over time among those 65+ years old. CONCLUSIONS: Trends in alcohol-attributable mortality may yield qualitatively different results based on the upper age limit for deaths set for these estimates. Global trends of alcohol-attributable mortality between 1997 and 2011 were influenced heavily by changes in the mixture of deaths across cardiovascular diseases. Trends for alcohol-attributable mortality and cross-country comparisons should be reported separately for 15-64 and 65+ year-olds. PMID- 26360122 TI - Cricopharyngeal dysfunction: A systematic review comparing outcomes of dilatation, botulinum toxin injection, and myotomy. AB - OBJECTIVES: Cricopharyngeal dysfunction may lead to severe dysphagia and aspiration. The objective of this systematic review was to evaluate the existing studies on the effectiveness of myotomy, dilatation, and botulinum toxin (BoT) injection in the management of cricopharyngeal dysphagia. METHODS: PubMed and Web of Science databases were searched to identify eligible studies by using the terms "cricopharyngeal dysfunction," "cricopharyngeal myotomy," "cricopharyngeal botox," "cricopharyngeal dilation," and their combinations from 1990 to 2013. This was supplemented by hand-searching relevant articles. Eligible articles were independently assessed for quality by two authors. Statistical analysis was performed. RESULTS: The database search revealed 567 articles. Thirty-two articles met eligibility criteria and were further evaluated. The reported success rates of BoT injections was between 43% and 100% (mean = 76%), dilation 58% and 100% (mean = 81%), and myotomy 25% and 100% (mean = 75%). In logistic regression analysis of the patient-weighted averages, the 78% success rate with myotomy was significantly higher than the 69% success rate with BoT injections (P = .042), whereas the intermediate success rate of 73% with dilation was not significantly different from that of either myotomy (P = .37) or BoT (P = .42). There was a statistically significant difference between endoscopic and open myotomy success rates (P = .0025). Endoscopic myotomy had a higher success rate, with a 2.2 odds ratio. CONCLUSIONS: The success rate of myotomy is significantly higher than the success rate of BoT injections in cricopharyngeal dysfunction. Moreover, endoscopic myotomy was found to have a higher success rate compared to open myotomy. PMID- 26360123 TI - Beta oscillations in freely moving Parkinson's subjects are attenuated during deep brain stimulation. AB - BACKGROUND: Investigations into the effect of deep brain stimulation (DBS) on subthalamic (STN) beta (13-30 Hz) oscillations have been performed in the perioperative period with the subject tethered to equipment. Using an embedded sensing neurostimulator, this study investigated whether beta power was similar in different resting postures and during forward walking in freely moving subjects with Parkinson's disease (PD) and whether STN DBS attenuated beta power in a voltage-dependent manner. METHODS: Subthalamic local field potentials were recorded from the DBS lead, using a sensing neurostimulator (Activa((r)) PC+S, Medtronic, Inc., Food and Drug Administration- Investigational Device Exemption (IDE)-, institutional review board-approved) from 15 PD subjects (30 STNs) off medication during lying, sitting, and standing, during forward walking, and during randomized periods of 140 Hz DBS at 0 V, 1 V, and 2.5/3 V. Continuous video, limb angular velocity, and forearm electromyography recordings were synchronized with neural recordings. Data were parsed to avoid any movement or electrical artifact during resting states. RESULTS: Beta power was similar during lying, sitting, and standing (P = 0.077, n = 28) and during forward walking compared with the averaged resting state (P = 0.466, n = 24), although akinetic rigid PD subjects tended to exhibit decreased beta power when walking. Deep brain stimulation at 3 V and at 1 V attenuated beta power compared with 0 V (P < 0.003, n = 14), and this was voltage dependent (P < 0.001). CONCLUSIONS: Beta power was conserved during resting and forward walking states and was attenuated in a voltage-dependent manner during 140-Hz DBS. Phenotype may be an important consideration if this is used for closed-loop DBS. PMID- 26360124 TI - Bullying risk in students with food allergy: Schoolteachers' awareness. PMID- 26360125 TI - Conversion of once-daily extended-release tacrolimus is safe in stable liver transplant recipients: A randomized prospective study. AB - Simplifying the therapeutic regimen of liver transplantation (LT) recipients may help prevent acute rejection and graft failure. The present study aimed to evaluate the efficacy and safety of conversion from twice-daily tacrolimus to once-daily extended-release tacrolimus under concurrent mycophenolate mofetil therapy in stable LT recipients. This randomized, prospective, controlled study included 91 patients who underwent LTs with at least 1 year of posttransplant follow-up. Conversion was made on a 1 mg to 1 mg basis. No incidences of biopsy proven acute rejection, graft failure, or death were reported in either group at 24 weeks. Median serum tacrolimus level of the study group was 20% less than that of the control group at 8 weeks. However, no significant differences regarding biochemical indicators of liver function or serum creatinine levels were observed between the 2 groups. Adverse event (AE) profiles were similar for both groups, with comparable incidences of AEs and serious AEs. No significant differences regarding efficacy or safety were observed between the once-daily tacrolimus and twice-daily tacrolimus groups of stable LT recipients. In conclusion, our study suggests that tacrolimus can be safely converted from a twice-daily regimen to a once-daily regimen in stable LT recipients. PMID- 26360126 TI - Photocyclodehydrofluorination. AB - Mallory-type photocyclization involves a series of photoreactions of stilbenes, o terphenyls and related derivatives, which undergo intramolecular cyclization via dihydrophenanthrene intermediates. In typical Mallory photocyclizations, oxidants are usually needed to produce the final phenanthrene-containing product. In the research described here, appropriately fluorinated stilbenes and o-terphenyls undergo ring closure and HF is eliminated. This photocyclodehydrofluorination (PCDHF) reaction is very useful to produce a wide range of selectively fluorinated polynuclear aromatic hydrocarbons that possess a phenanthrene (or heterocyclic analogue of phenanthrene) substructure. These fluorinated products are of great interest in various aspects of the materials science. PMID- 26360127 TI - Hyperpigmentation Induced by Combination Therapy With Telmisartan Hydrochlorothiazide. PMID- 26360128 TI - Biological activities and pharmacokinetics of aconitine, benzoylaconine, and aconine after oral administration in rats. AB - Aconitine (AC), benzoylaconine (BAC), and aconine (ACN) are three representative alkaloids in Aconitum tubers. Knowing that the drug disposal process in vivo is closely related to the toxicity and efficacy of a drug, it is important to classify the disposal properties of these alkaloids. In this study, the pharmacokinetics of the three alkaloids was investigated. The results showed that the three alkaloids could be quickly absorbed, especially BAC, whose Tmax was 0.31 +/- 0.17 h. Their Cmax was 10.99, 3.99, and 4.29 ng.mL(-1) respectively, indicating that AC had better absorption than BAC and ACN. Subsequently, we further investigated their absorption mechanism using the Caco-2 cell monolayer model in vitro. The results showed that they were poorly absorbed, and the absorption of AC and BAC was inhibited by P-gp, while the absorption of ACN was in a form of passive diffusion. The t1/2 of AC, BAC and ACN was 1.41, 9.49, and 3.32 h, respectively, indicating that the metabolic or excretion rate of AC was quicker than that of BAC and ACN. Therefore, their metabolic stability was further investigated by using rat liver microsomes in vitro, which showed that AC was easier to be metabolized than BAC and ACN. The excretion experiments showed that AC and ACN were primarily excreted in urine, while BAC was excreted in faeces. In addition, the results of tissue distribution experiments showed that the three alkaloids distributed throughout all the organs, although the distribution rate of AC was slower than that of BAC and ACN. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26360129 TI - Ocular pharmacology. AB - Ophthalmic diseases include both those analogous to systemic diseases (eg, inflammation, infection, neuronal degeneration) and not analogous (eg, cataract, myopia). Many anterior segment diseases are treated pharmacologically through eye drops, which have an implied therapeutic index of local therapy. Unlike oral dosage forms administered for systemic diseases, eyedrops require patients not only to adhere to treatment, but to be able to accurately perform-ie, instill drops correctly. Anatomical and physiological barriers make topical delivery to the anterior chamber challenging-in some cases more challenging than absorption through the skin, nasal passages, or gut. Treatment of the posterior segment (eg, vitreous, retina, choroid, and optic nerve) is more challenging due to additional barriers. Recently, intravitreal injections have become a standard of care with biologics for the treatment of macular degeneration and other diseases. Although the eye has esterases, hydroxylases, and transporters, it has relatively little CYP450 enzymes. Because it is challenging to obtain drug concentrations at the target site, ocular clinical pharmacokinetics, and thus pharmacokinetic pharmacodynamic interactions, are rarely available. Ophthalmic pharmaceuticals require consideration of solubility, physiological pH, and osmolarity, as well as sterility and stability, which in turn requires optimal pharmaceutics. Although applied locally, ocular medications may be absorbed systemically, which results in morbidity and mortality (eg, systemic hypotension, bronchospasm, and bradycardia). PMID- 26360130 TI - Analysis of bone conducted sound over the cranial vault. PMID- 26360131 TI - Genome-scale identification of miRNA-mRNA and miRNA-lncRNA interactions in domestic animals. AB - Domestic animals show considerable genetic diversity. Previous studies suggested that animal phenotypes were affected by miRNA-mRNA interplay, but these studies focused mainly on the analysis of one or several miRNA-mRNA interactions. However, in this study, we investigated miRNA-mRNA and miRNA-lncRNA interactions on a genomic scale using miranda and targetscan algorithms. There has been strong directional artificial selection practiced during the domestication of animals. Thus, we investigated SNPs that were located in miRNAs and miRNA binding sites and found that several SNPs located in 3'-UTRs of mRNAs had the potential to affect miRNA-mRNA interactions. In addition, a database, named miRBond, was developed to provide visualization, analysis and downloading of the resulting datasets. Our results open the way to further experimental verification of miRNA mRNA and miRNA-lncRNA interactions as well as the influence of SNPs upon such interplay. PMID- 26360132 TI - Investigating the Role of Conformational Effects on Laccase Stability and Hyperactivation under Stress Conditions. AB - Fungal laccase from Steccherinum ochraceum 1833 displays remarkable stability under different harsh conditions: organic/buffer mixtures, thermal treatment, and microwave radiation. The behavior is particularly significant in the light of the sharp inactivation observed for two different fungal laccases. Laccase from S. ochraceum 1833 also displays hyperactivation under mild thermal treatment (60 degrees C). Molecular dynamics simulations at 80 degrees C explained how this laccase retains the geometry of the electron transfer pathway, thereby assuring electron transfer through the copper ions and thus maintaining its catalytic activity at high temperature. Spectroscopic studies revealed that the thermal activation corresponds to specific conformational changes in the protein. The results indicate that this laccase is potentially applicable under denaturing conditions that might be beneficial for the biotransformation of recalcitrant substrates. PMID- 26360133 TI - Atypical Femoral Fracture in Rheumatoid Arthritis Patients Treated With Bisphosphonates: A Nested Case-Control Study. AB - OBJECTIVE: To examine the clinical characteristics of atypical femoral fracture (AFF) and to determine the risk factors for and clinical outcomes of AFFs in rheumatoid arthritis (RA) patients treated with bisphosphonates (BPs). METHODS: A nested case-control study was conducted using data derived from the medical records of all RA patients treated with BPs at Seoul St. Mary's Hospital, a tertiary rheumatology center, from January 1, 2008 to December 31, 2014. All of the patients with RA and had been treated with BPs for at least 1 year. Ten RA patients with AFF were identified, and each of these patients (cases) was age- and sex-matched with 4 RA patients without AFF (controls). RESULTS: Five hundred fifty-two RA patients had BP exposure. Of the 10 with AFF, all were female (mean +/- SD age 66.3 +/- 8.7 years), and 90% of cases involved fracture of the proximal femur. The mean +/- SD length of BP exposure in patients with AFF was 7.4 +/- 3.2 years. Compared with controls, patients with AFF had a longer exposure to BPs and more often had a femorotibial angle of <175 degrees (both P < 0.001). There were no differences in RA duration, medications taken during the previous 6 months, and bone mineral density in the femur and lumbar spine between patients with and those without AFF. Multivariate logistic analyses identified longer BP exposure (odds ratio 2.386 [95% confidence interval 1.066-5.343]) as being associated with an increased risk of AFF. CONCLUSION: RA patients who have a valgus deformity and are receiving long-term BP treatment are at higher risk of AFF compared with matched control patients with RA. These patients should be carefully followed up with hip radiography or dual x-ray absorptiometry. PMID- 26360134 TI - Photoredox-Catalyzed Stereoselective Conversion of Alkynes into Tetrasubstituted Trifluoromethylated Alkenes. AB - A regio- and stereoselective synthesis of trifluoromethylated alkenes bearing four different substituents has been developed. Stereocontrolled sulfonyloxytrifluoromethylation of unsymmetric internal alkynes with an electrophilic CF3 reagent, namely the triflate salt of the Yagupol'skii-Umemoto reagent, in the presence of an Ir photoredox catalyst under visible-light irradiation afforded trifluoromethylalkenyl triflates with well-predictable stereochemistry resulting from anti addition of the trifluoromethyl and triflate groups. Subsequent palladium-catalyzed cross-couplings led to tetrasubstituted trifluoromethylated alkenes in a highly stereoselective manner. The present method is the first example of a facile one-pot synthesis of tetrasubstituted trifluoromethylated alkenes from simple alkynes. PMID- 26360135 TI - Influenza: Can we cope better with the unpredictable? AB - Seasonal influenza vaccines are unique because they are regularly reformulated and prepared in anticipation of the upcoming influenza season. Selection of vaccine strains occurs in advance of the influenza season, allowing time for vaccine production. Influenza viruses constantly evolve, and mismatches between vaccine strains and circulating strains have occurred in the past, impacting on vaccine effectiveness. The public health impact of a mismatch depends on multiple factors including strain virulence and transmission dynamics, pre-existing population immunity to the drift strain, and cross-reactivity induced by vaccination. Influenza vaccine effectiveness thus varies unpredictably from year to year, and may differ across European and northern American regions. Here we highlight the unpredictability associated with influenza virus circulation and present a comprehensive picture of circulating influenza strains in the northern hemisphere as compared to WHO recommendations for vaccine strains over the last 15 y. In years when vaccine mismatch occurs, such as the 2014-15 influenza season, public health agencies continue to recommend influenza vaccination as the preferred means by which to protect against influenza and influenza-associated complications. Research is on-going to optimise strain selection and vaccine composition to improve effectiveness. PMID- 26360136 TI - Attenuated Total Reflectance-Fourier Transform Infrared Spectroscopy on Intact Dried Leaves of Sage (Salvia officinalis L.): Accelerated Chemotaxonomic Discrimination and Analysis of Essential Oil Composition. AB - Sage (Salvia officinalis L.) is cultivated worldwide for its aromatic leaves, which are used as herbal spice, and for phytopharmaceutical applications. Fast analytical strategies for essential oil analysis, performed directly on plant material, would reduce the delay between sampling and analytical results. This would enhance product quality by improving technical control of cultivation. The attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) method described here provides a reliable calibration model for quantification of essential oil components [EOCs; R(2) = 0.96; root-mean-square error of cross validation (RMSECV) = 0.249 mL 100 g(-1) of dry matter (DM); and range = 1.115 5.280 mL 100 g(-1) of DM] and main constituents [e.g., alpha-thujone/beta thujone; R(2) = 0.97/0.86; RMSECV = 0.0581/0.0856 mL 100 g(-1) of DM; and range = 0.010-1.252/0.005-0.893 mL 100 g(-1) of DM] directly on dried intact leaves of sage. Except for drying, no further sample preparation is required for ATR-FTIR, and the measurement time of less than 5 min per sample contrasts with the most common alternative of hydrodistillation followed by gas chromatography analysis, which can take several hours per sample. PMID- 26360137 TI - Circulating Apoptotic Microparticles in Systemic Lupus Erythematosus Patients Drive the Activation of Dendritic Cell Subsets and Prime Neutrophils for NETosis. AB - OBJECTIVE: Circulating chromatin-containing apoptotic material and/or neutrophil extracellular traps (NETs) have been proposed to be an important driving force for the antichromatin autoimmune response in patients with systemic lupus erythematosus (SLE). The aim of this study was to determine the exact nature of microparticles in the circulation of SLE patients and to assess the effects of the microparticles on the immune system. METHODS: We analyzed microparticles isolated from the plasma of patients with SLE, rheumatoid arthritis (RA), and systemic sclerosis (SSc), as well as from healthy subjects. The effects of the microparticles on blood-derived dendritic cells (DCs) and neutrophils were assessed by flow cytometry, enzyme-linked immunosorbent assay, and immunofluorescence microscopy. RESULTS: In SLE patients, we identified microparticles that were highly positive for annexin V and apoptosis-modified chromatin that were not present in healthy subjects or in RA or SSc patients. These microparticles were mostly CD31+/CD45- (endothelial), partly CD45+/CD66b+ (granulocyte), and negative for B and T cell markers. Microparticles isolated from the plasma of SLE patients increased the expression of the costimulatory surface molecules CD40, CD80, CD83, and CD86 and the production of proinflammatory cytokines interleukin-6, tumor necrosis factor, and interferon alpha by blood-derived plasmacytoid DCs (PDCs) and myeloid DCs (MDCs). SLE microparticles also primed blood-derived neutrophils for NETosis. Microparticles from healthy subjects and from RA or SSc patients exhibited no significant effects on MDCs, PDCs, and NETosis. CONCLUSION: Circulating microparticles in SLE patients include a population of apoptotic cell-derived microparticles that has proinflammatory effects on PDCs and MDCs and enhances NETosis. These results underline the important role of apoptotic microparticles in driving the autoimmune response in SLE patients. PMID- 26360138 TI - A retrospective review of the incidence of various complications in different delayed breast reconstruction methods. AB - BACKGROUND: Breast reconstruction is a common standard procedure in many centres after breast cancer surgery. The aim of the present study was to investigate and compare the incidence of various complications in different reconstruction methods. METHOD: Six hundred and eighty-five patients were retrospectively classified into five groups: (1) Deep inferior epigastric perforator flap (DIEP), (2) latissimus dorsi flap (LD), (3) lateral thoracodorsal flap (LTDF), (4) expander with secondary implant (EXP), and (5) direct implant (DI). Demographic and perioperative data, the incidence of complications, and follow-up data were collected. RESULTS: There was a significant difference between groups regarding overall early complications (p < 0.001). The DIEP group had the highest incidence of overall complications (50.0%) (p < 0.05). DIEP also had the highest incidence of fat necrosis (18.3%), skin necrosis (22.1%), and incidence of reoperation for complications (26.9%) compared to the other reconstruction methods. In the entire group of patients, the overall incidence of late complications (occurring >30 days after surgery) that needed surgical corrections was 54.7%. The incidence of late complications was 46.2% for DIEP, 66.4% for LD, 74.8% for LTDF, 44.9% for EXP, and 62.9% for DI. The DIEP group had higher incidences of late local complications (fat necrosis, skin necrosis, haematoma, seroma, and wound rupture combined), and scars requiring treatment than the other reconstruction methods. CONCLUSION: Meticulous registration of incidence of different complications in five different breast reconstruction methods revealed high complication rates with all methods. The differences in incidence of complications were related to the operation method used. Based on these results, careful individual planning of a breast reconstruction is mandatory. PMID- 26360140 TI - Is the lateral jack-knife position responsible for cases of transient neurapraxia? AB - OBJECTIVE: The lateral jack-knife position is often used during transpsoas surgery to improve access to the spine. Postoperative neurological signs and symptoms are very common after such procedures, and the mechanism is not adequately understood. The objective of this study is to assess if the lateral jack-knife position alone can cause neurapraxia. This study compares neurological status at baseline and after positioning in the 25 degrees right lateral jack knife (RLJK) and the right lateral decubitus (RLD) position. METHODS: Fifty healthy volunteers, ages 21 to 35, were randomly assigned to one of 2 groups: Group A (RLD) and Group B (RLJK). Motor and sensory testing was performed prior to positioning. Subjects were placed in the RLD or RLJK position, according to group assignment, for 60 minutes. Motor testing was performed immediately after this 60-minute period and again 60 minutes thereafter. Sensory testing was performed immediately after the 60-minute period and every 15 minutes thereafter, for a total of 5 times. Motor testing was performed by a physical therapist who was blinded to group assignment. A follow-up call was made 7 days after the positioning sessions. RESULTS: Motor deficits were observed in the nondependent lower limb in 100% of the subjects in Group B, and no motor deficits were seen in Group A. Statistically significant differences (p < 0.05) were found between the 2 groups with respect to the performance on the 10-repetition maximum test immediately immediately and 60 minutes after positioning. Subjects in Group B had a 10%-70% (average 34.8%) decrease in knee extension strength and 20%-80% (average 43%) decrease in hip flexion strength in the nondependent limb. Sensory abnormalities were observed in the nondependent lower limb in 98% of the subjects in Group B. Thirty-six percent of the Group B subjects still exhibited sensory deficits after the 60-minute recovery period. No symptoms were reported by any subject during the follow-up calls 7 days after positioning. CONCLUSIONS: Twenty five degrees of right lateral jack-knife positioning for 60 minutes results in neurapraxia of the nondependent lower extremity. Our results support the hypothesis that jack-knife positioning alone can cause postoperative neurological symptoms. PMID- 26360139 TI - Medial prefrontal cortex TRPV1 channels modulate the baroreflex cardiac activity in rats. AB - BACKGROUND AND PURPOSE: The ventral portion of the medial prefrontal cortex (vMPFC) comprises the infralimbic (IL), prelimbic (PL) and dorsopenducular (DP) cortices. The IL and PL regions facilitate the baroreceptor reflex arc. This facilitatory effect on the baroreflex is thought to be mediated by vMPFC glutamatergic transmission, through NMDA receptors. The glutamatergic transmission can be modulated by other neurotransmitters, such as the endocannabinoids, which are agonists of the TRPV1 receptor. TRPV1 channels facilitate glutamatergic transmission in the brain. Thus, we hypothesized that TRPV1 receptors in the vMPFC enhance the cardiac baroreflex response. EXPERIMENTAL APPROACH: Stainless steel guide cannulae were bilaterally implanted into the vMPFC of male Wistar rats. Afterwards, a catheter was inserted into the femoral artery, for recording MAP and HR, and into the femoral vein for assessing baroreflex activation. KEY RESULTS: Microinjections of the TRPV1 receptor antagonists capsazepine and 6-iodo-nordihydrocapsaicin (6-IODO) into the vMPFC reduced the cardiac baroreflex activity in unanaesthetized rats. Capsaicin microinjected into the vMPFC increased the cardiac baroreflex activity in unanaesthetized rats. When an ineffective dose of the TRPV1 receptor antagonist 6 IODO was used, the capsaicin-induced increase in the cardiac baroreflex response was abolished. The higher doses of capsaicin administered into the vMPFC after the ineffective dose of 6-IODO displaced the dose-response curve of the baroreflex parameters to the right, with no alteration in the maximum effect of capsaicin. CONCLUSIONS AND IMPLICATIONS: The results of the present study show that stimulation of the TRPV1 receptors in the vMPFC increases the cardiac baroreceptor reflex response. PMID- 26360141 TI - Preoperative narcotic utilization: accuracy of patient self-reporting and its association with postoperative narcotic consumption. AB - OBJECTIVE: Little is known about the accuracy of reporting of preoperative narcotic utilization in spinal surgery. As such, the purpose of this study is to compare postoperative narcotic consumption between preoperative narcotic utilizers who do and do not accurately self-report preoperative utilization. METHODS: Patients who underwent anterior cervical discectomy and fusion, minimally invasive lumbar discectomy, or minimally invasive transforaminal lumbar interbody fusion procedures between 2013 and 2014 were prospectively identified. The accuracy of self-reporting preoperative narcotic consumption was determined utilizing the Illinois Prescription Monitoring Program. Total inpatient narcotic consumption during postoperative Days 0 and 1 was compared according to the demographics and preoperative narcotic reporting accuracy. Similarly, the proportion of patients who continued to be dependent on narcotic medications at each postoperative visit was compared according to the demographics and preoperative narcotic reporting accuracy. RESULTS: A total of 195 patients met the inclusion criteria. Of these, 25% did not use narcotics preoperatively, while 47% and 28% did do so with accurate and inaccurate reporting, respectively. Patients who used narcotics preoperatively were more likely to demonstrate elevated inpatient narcotic consumption (adjusted RR 5.3; 95% CI 1.4-20.1; p = 0.013). However, such patients were no more or less likely to be dependent on narcotic medications at the first (p = 0.618) or second (p = 0.798) postoperative visit. Among patients who used narcotics preoperatively, no differences were demonstrated in terms of inpatient narcotic consumption (p = 0.182) or narcotic dependence following the first (p = 0.982) or second (p = 0.866) postoperative visit according to the self-reported accuracy of preoperative narcotic utilization. The only preoperative factors that were independently associated with elevated inpatient narcotic consumption were workers' compensation status and procedure type. The only preoperative factors that were independently associated with narcotic dependence at the first postoperative visit were female sex, workers' compensation status, and procedure type. The only preoperative factor that was independently associated with narcotic dependence at the second postoperative visit was procedure type. CONCLUSIONS: The findings suggest that determining the actual preoperative narcotic utilization in patients who undergo spine surgery may help optimize postoperative pain management. Approximately 75% of patients used narcotics preoperatively. Patients who used narcotics preoperatively demonstrated significantly higher inpatient narcotic consumption, but this difference did not persist following discharge. Finally, postoperative narcotic consumption (inpatient and following discharge) was independent of the self-reported accuracy of preoperative narcotic utilization. Taken together, these findings suggest that corroboration between the patient's self-reported preoperative narcotic utilization and other sources of information (e.g., family members and narcotic registries) may be clinically valuable with respect to minimizing narcotic requirements, thereby potentially improving the management of postoperative pain. PMID- 26360142 TI - Incidence of microbiological contamination of local bone autograft used in posterior lumbar interbody fusion and its association with postoperative spinal infection. AB - OBJECTIVE: The aim of this study was to examine the results of microbiological cultures from local bone autografts used in posterior lumbar interbody fusion (PLIF) and to identify their association with postoperative spinal infection. METHODS: The authors retrospectively evaluated cases involving 328 patients who had no previous spinal surgeries and underwent PLIF for degenerative diseases with a minimum 1-year follow-up. Local bone was obtained during laminectomy, and microbiological culture was performed immediately prior to bone grafting. The associations between culture results from local bone autografts and postoperative spinal infections were evaluated. RESULTS: The contamination rate of local bone was 4.3% (14 of 328 cases). Coagulase-negative Staphylococcus (29%) was the most common contaminant isolated, followed by Streptococcus species and methicillin sensitive Staphylococcus aureus. Of 14 patients with positive culture results, 5 (35.7%) had postoperative spinal infections and were treated with intravenous antibiotics for a minimum of 4 weeks. One of these 5 patients also underwent reoperation for debridement during this 4-week period. Regardless of the microbiological culture results, the infection rate after PLIF with local bone autograft was 2.4% (8 of 328 cases), with 5 (62.5%) of 8 patients showing positive results on autograft culture. CONCLUSIONS: The incidence of contamination of local bone autograft during PLIF was considerable, and positive culture results were significantly associated with postoperative spinal infection. Special attention focused on the preparation of local bone for autograft and its microbiological culture will be helpful for the control of postoperative spinal infection. PMID- 26360143 TI - Patient-specific factors affecting hospital costs in lumbar spine surgery. AB - OBJECTIVE: Health care-related costs after lumbar spine surgery vary depending on procedure type and patient characteristics. Age, body mass index (BMI), number of spinal levels, and presence of comorbidities probably have significant effects on overall costs. The present study assessed the impact of patient characteristics on hospital costs in patients undergoing elective lumbar decompressive spine surgery. METHODS: This study was a retrospective review of elective lumbar decompression surgeries, with a focus on specific patient characteristics to determine which factors drive postoperative, hospital-related costs. Records between January 2010 and July 2012 were searched retrospectively. Only elective lumbar decompressions including discectomy or laminectomy were included. Cost data were obtained using a database that allows standardization of a list of hospital costs to the fiscal year 2013-2014. The relationship between cost and patient factors including age, BMI, and American Society of Anesthesiologists (ASA) Physical Status Classification System grade were analyzed using Student t tests, ANOVA, and multivariate regression analyses. RESULTS: There were 1201 patients included in the analysis, with a mean age of 61.6 years. Sixty percent of patients in the study were male. Laminectomies were performed in 557 patients (46%) and discectomies in 644 (54%). Laminectomies led to an increased hospital stay of 1.4 days (p < 0.001) and increased hospital costs by $1523 (p < 0.001) when compared with discectomies. For laminectomies, age, BMI, ASA grade, number of levels, and durotomy all led to significantly increased hospital costs and length of stay on univariate analysis, but ASA grade and presence of a durotomy did not maintain significance on multivariate analysis for hospital costs. For a laminectomy, patient age >= 65 years was associated with a 0.6-day increased length of stay and a $945 increase in hospital costs when compared with patient age < 65 years (p < 0.001). A durotomy during a laminectomy increased length of stay by 1.0 day and increased hospital costs by $1382 (p < 0.03). For discectomies, age, ASA grade, and durotomy were significantly associated with increased hospital costs on univariate analysis, but BMI was not. Only age and presence of a durotomy maintained significance on multivariate analysis. There was a significant increase in hospital length of stay in patients undergoing discectomy with increasing age, BMI, ASA grade, and presence of a durotomy on univariate analysis. However, only age and presence of a durotomy maintained significance on multivariate analysis. For discectomies, age >= 65 years was associated with a 0.7-day increased length of stay (p < 0.001) and an increase of $931 in postoperative hospital costs (p < 0.01) when compared with age < 65 years. CONCLUSIONS: Patient factors such as age, BMI, and comorbidities have significant and measurable effects on the postoperative hospital costs of elective lumbar decompression spinal surgeries. Knowledge of how these factors affect costs will become important as reimbursement models change. PMID- 26360144 TI - Postoperative survival and functional outcomes for patients with metastatic gynecological cancer to the spine: case series and review of the literature. AB - OBJECTIVE: Spinal metastases from gynecological cancers are rare, with few cases reported in the literature. In this study, the authors examine a series of patients with spinal metastases from gynecological cancer and review the literature. METHODS: The cases of 6 consecutive patients who underwent spine surgery for metastatic gynecological cancer between 2007 and 2012 at a single institution were retrospectively reviewed. The recorded demographic, operative, and postoperative factors were reviewed, and the functional outcomes were determined by change in Karnofsky Performance Scale and the American Spine Injury Association (ASIA) score during follow-up. A systematic review of the literature was also performed to evaluate outcomes for patients with similar gynecological metastases to the spine. RESULTS: In this series, details regarding metastatic gynecological cancers to the spine are as follows: 2 patients with cervical cancer (both presented at age 46 years, mean postoperative survival of 32 months), 2 patients with endometrial cancer (mean age of 40 years, mean postoperative survival of 26 months), and 2 patients with leiomyosarcoma (mean age of 44 years, mean postoperative survival of 20 months). All patients presented with pain, and no complications were noted following surgery. All patients with known follow-up had stable or improved neurological outcomes, performance status, and improved pain, without local recurrence of tumor. Overall median survival after diagnosis of metastatic spine lesions for all cases in the literature as well as those treated by the authors was 15 months. When categorized by type, median survival of patients with cervical cancer (n = 2), endometrial cancer (n = 26), and leiomyosarcoma (n = 16) was 32, 10, and 22.5 months, respectively. CONCLUSIONS: Gynecological cancers metastasizing to the spine are rare. In this series, overall survival following diagnosis of spinal metastasis and surgery was 27 months, with cervical cancer, endometrial cancer, and leiomyosarcoma survival being 32, 26, and 20 months, respectively. Combined with literature cases, survival differs depending on primary histology, with decreasing survival from cervical cancer (32 months) to leiomyosarcoma (22.5 months) to endometrial cancer (10 months). Integrating such information with other patient factors may more accurately guide decision making regarding management of such spinal lesions. PMID- 26360145 TI - A new technique of bone cement augmentation via the disc space for percutaneous pedicle screw fixation. AB - OBJECTIVE: In elderly patients with severe osteoporosis, instrumented lumbar interbody fusion may result in fixation failure or nonunion because of decreased pedicle screw pullout strength or increased interbody graft subsidence risk. Thus, given its many advantages, percutaneous pedicle screw fixation with cement augmentation can be an effective method to use in elderly patients. The authors report on an easy, safe, and economical technique for bone cement augmentation using a bone biopsy needle inserted into the disc space in 2 osteoporotic patients who were treated with posterior interbody fusion and percutaneous pedicle screw fixation. METHODS: Two elderly patients who complained of back pain and intermittent neurological claudication underwent posterior interbody fusion with percutaneous pedicle screw fixation. After routinely assembling rods on the screws, a bone biopsy needle was inserted into the disc space via the operative field; the needle was then placed around the tips of the screws using fluoroscopic radiography for guidance. Bone cement was injected through the bone biopsy needle, also under fluoroscopic radiography guidance. RESULTS: Both patients' symptoms improved after the operation, and there was no evidence of cage subsidence or screw loosening at the 4-month follow-up. CONCLUSIONS: The indirect technique of bone cement augmentation via the disc space for percutaneous screw fixation could be an easy, safe, and economical method. PMID- 26360146 TI - Postoperative posterior lumbar muscle changes and their relationship to segmental motion preservation or restriction: a randomized prospective study. AB - OBJECTIVE: To date, it remains unclear whether the preservation of segmental motion by total disc replacement (TDR) or motion restriction by stand-alone anterior lumbar interbody fusion (ALIF) have an influence on postoperative degeneration of the posterior paraspinal muscles or the associated clinical results. Therefore, the purpose of the present prospective randomized study was to evaluate the clinical parameters and 3D quantitative radiological changes in the paraspinal muscles of the lumbar spine in surgically treated segments and superior adjacent segments after ALIF and TDR. METHODS: A total of 50 patients with chronic low-back pain caused by single-level intervertebral disc degeneration (Pfirrmann Grade >= III) and/or osteochondrosis (Modic Type <= 2) without symptomatic facet joint degeneration (Fujiwara Grade <= 2, infiltration test) of the segments L4-5 or L5-S1 were randomly assigned to 2 treatment groups. Twenty-five patients were treated with a stand-alone ALIF and the remaining 25 patients underwent TDR. For ALIF and TDR, a retroperitoneal approach was used. At 1 week and at 12 months after surgery, CT was used to analyze paraspinal lumbar muscle tissue volume and relative fat content. Residual muscle tissue volume at 12 months and change in the relative fat content were compared between the groups. In addition, clinical parameters (visual analog scale [VAS] for low-back pain and Oswestry Disability Index [ODI] Questionnaire Version 2 for function) were compared. RESULTS: Compared with 1 week after surgery, the radiological analysis at 12 months revealed a small decrease in the posterior muscle volume (the mean decrease was < 2.5%), along with a small increase in the relative fat content (the mean increase was < 1.9%), in both groups at the index and superior adjacent segments. At the adjacent segment, the ALIF group presented significantly less muscle tissue volume atrophy and a smaller increase in fat content compared with the TDR group. At final follow-up, the clinical parameters related to pain and function were significantly improved in both groups compared with 1 week postsurgery, but there were no differences between the groups. CONCLUSIONS: Motion restriction via stand-alone ALIF and motion preservation via TDR both present small changes in the posterior lumbar paraspinal muscles with regard to volume atrophy or fatty degeneration at the index and superior adjacent segments. Therefore, although the clinical outcome was not affected by the observed muscular changes, the authors concluded that the expected negative influence of motion restriction on the posterior muscles compared with motion preservation does not occur on a clinically relevant level. PMID- 26360147 TI - Association between preoperative cervical sagittal deformity and inferior outcomes at 2-year follow-up in patients with adult thoracolumbar deformity: analysis of 182 patients. AB - OBJECTIVE: A high prevalence of cervical deformity (CD) has been identified among adult patients with thoracolumbar spinal deformity undergoing surgical treatment. The clinical impact of this is uncertain. This study aimed to quantify the differences in patient-reported outcomes among patients with adult spinal deformity (ASD) based on presence of CD prior to treatment. METHODS: A retrospective review was conducted of a multicenter prospective database of patients with ASD who underwent surgical treatment with 2-year follow-up. Patients were grouped by the presence of preoperative CD: 1) cervical positive sagittal malalignment (CPSM) C2-7 sagittal vertical axis >= 4 cm; 2) cervical kyphosis (CK) C2-7 angle > 0; 3) CPSM and CK (BOTH); and 4) no baseline CD (NONE). Health-related quality of life (HRQOL) scores included the Physical Component Summary and Mental Component Summary (PCS and MCS) scores of the 36 Item Short Form Health Survey (SF-36), Oswestry Disability Index (ODI), Scoliosis Research Society-22 questionnaire (SRS-22), and minimum clinically important difference (MCID) of these scores at 2 years. Standard radiographic measurements were conducted for cervical, thoracic, and thoracolumbar parameters. RESULTS: One hundred eighty-two patients were included in this study: CPSM, 45; CK, 37; BOTH, 16; and NONE, 84. Patients with preoperative CD and those without had similar baseline thoracolumbar radiographic measurements and similar correction rates at 2 years. Patients with and without preoperative CD had similar baseline HRQOL and on average both groups experienced some HRQOL improvement. However, those with preoperative CPSM had significantly worse postoperative ODI, PCS, SRS-22 Activity, SRS-22 Appearance, SRS-22 Pain, SRS-22 Satisfaction, and SRS-22 Total score, and were less likely to meet MCID for ODI, PCS, SRS-22 Activity, and SRS 22 Pain scores with the following ORs and 95% CIs: ODI 0.19 (0.07-0.58), PCS 0.17 (0.06-0.47), SRS-22 Activity 0.23 (0.09-0.62), SRS-22 Pain 0.20 (0.08-0.53), and SRS-22 Appearance 0.34 (0.12-0.94). Preoperative CK did not have an effect on outcomes. Interestingly, despite correction of the thoracolumbar deformity, 53.3% and 51.4% of patients had persistent CPSM and persistent CK, respectively. CONCLUSIONS: Patients with thoracolumbar deformity without preoperative CD are likely to have greater improvements in HRQOL after surgery than patients with concomitant preoperative CD. Cervical positive sagittal alignment in adult patients with thoracolumbar deformity is strongly associated with inferior outcomes and failure to reach MCID at 2-year follow-up despite having similar baseline HRQOL to patients without CD. This was the first study to assess the impact of concomitant preoperative cervical malalignment in adult patients with thoracolumbar deformity. These results can help surgeons educate patients at risk for inferior outcomes and direct future research to identify an etiology and improve patient outcomes. Investigation into the etiology of the baseline cervical malalignment may be warranted in patients who present with thoracolumbar deformity. PMID- 26360148 TI - Effects of methylene blue on postoperative low-back pain and functional outcomes after lumbar open discectomy: a triple-blind, randomized placebo-controlled trial. AB - OBJECTIVE: Despite advances in surgical and anesthesiology techniques, many patients continue to experience postoperative pain after lumbar disc operations. This study aims to investigate the effects of methylene blue (MB) on preventing postoperative low-back pain (LBP) with or without radicular pain and improving the quality of life (QOL) in patients undergoing lumbar open discectomy. METHODS: This is a prospective, randomized, triple-blind, placebo-controlled clinical trial, which was conducted at Shiraz University of Medical Sciences between July 2011 to January 2012. Of a total of 130 patients, 115 were eligible for participation; 56 received 1 ml of MB solution at a concentration of 0.5% (MB group) and 59 received an equivalent volume of normal saline (control group). Primary outcomes were the control of LBP with or without radicular pain, which was evaluated preoperatively and at 24 hours and 3 months after surgery with the use of a visual analog scale (VAS), and the improvement of QOL, which was assessed preoperatively and 3 months postoperatively by means of the Persian translation of the Oswestry Disability Index questionnaire. RESULTS: The mean VAS scores for LBP were significantly lower in the MB group compared with the control group at 24 hours (1.25 +/- 0.97 vs 2.80 +/- 0.69, p < 0.001) and 3 months (1.02 +/- 1.29 vs 2.07 +/- 1.10, p = 0.019) after treatment. The mean radicular pain scores decreased significantly in the 2 groups at 24 hours after surgery, but the mean radicular pain score was significantly lower in the MB-treated patients than the control group. However, the difference between radicular pain scores in the MB group (1 +/- 1.1) and the control group (1.2 +/- 1) was not statistically significant (p = 0.64). The reduction in LBP was greater in the MB group than the control group (8.11 +/- 1.74 vs 6.07 +/- 1.52, p = 0.023, CI 95% -1.37 to -0.10). The functional QOL improved significantly 3 months after the operation in both groups (p < 0.001). Moderate disability occurred more frequently in the control group than in the MB group (14.5% vs 7.7%, p = 0.004). No toxicity, adverse effects, or complications were found in the group of patients treated with MB injection. CONCLUSIONS: A single dose of MB (1 ml 0.5%) for coating the dura and surrounding tissues (facet and muscle) shows promising results in terms of safety, reduction of postoperative pain, and functional outcome compared with placebo. PMID- 26360149 TI - The Different Clinical Faces of Obstructive Sleep Apnea (OSA), OSA in Older Adults as a Distinctly Different Physiological Phenotype, and the Impact of OSA on Cardiovascular Events after Coronary Artery Bypass Surgery. PMID- 26360154 TI - Ensemble clustering in visual working memory biases location memories and reduces the Weber noise of relative positions. AB - People seem to compute the ensemble statistics of objects and use this information to support the recall of individual objects in visual working memory. However, there are many different ways that hierarchical structure might be encoded. We examined the format of structured memories by asking subjects to recall the locations of objects arranged in different spatial clustering structures. Consistent with previous investigations of structured visual memory, subjects recalled objects biased toward the center of their clusters. Subjects also recalled locations more accurately when they were arranged in fewer clusters containing more objects, suggesting that subjects used the clustering structure of objects to aid recall. Furthermore, subjects had more difficulty recalling larger relative distances, consistent with subjects encoding the positions of objects relative to clusters and recalling them with magnitude-proportional (Weber) noise. Our results suggest that clustering improved the fidelity of recall by biasing the recall of locations toward cluster centers to compensate for uncertainty and by reducing the magnitude of encoded relative distances. PMID- 26360153 TI - The perceptual processing capacity of summary statistics between and within feature dimensions. AB - The simultaneous-sequential method was used to test the processing capacity of statistical summary representations both within and between feature dimensions. Sixteen gratings varied with respect to their size and orientation. In Experiment 1, the gratings were equally divided into four separate smaller sets, one of which with a mean size that was larger or smaller than the other three sets, and one of which with a mean orientation that was tilted more leftward or rightward. The task was to report the mean size and orientation of the oddball sets. This therefore required four summary representations for size and another four for orientation. The sets were presented at the same time in the simultaneous condition or across two temporal frames in the sequential condition. Experiment 1 showed evidence of a sequential advantage, suggesting that the system may be limited with respect to establishing multiple within-feature summaries. Experiment 2 eliminates the possibility that some aspect of the task, other than averaging, was contributing to this observed limitation. In Experiment 3, the same 16 gratings appeared as one large superset, and therefore the task only required one summary representation for size and another one for orientation. Equal simultaneous-sequential performance indicated that between-feature summaries are capacity free. These findings challenge the view that within feature summaries drive a global sense of visual continuity across areas of the peripheral visual field, and suggest a shift in focus to seeking an understanding of how between-feature summaries in one area of the environment control behavior. PMID- 26360155 TI - Foveal input is not required for perception of crowd facial expression. AB - The visual system extracts average features from groups of objects (Ariely, 2001; Dakin & Watt, 1997; Watamaniuk & Sekuler, 1992), including high-level stimuli such as faces (Haberman & Whitney, 2007, 2009). This phenomenon, known as ensemble perception, implies a covert process, which would not require fixation of individual stimulus elements. However, some evidence suggests that ensemble perception may instead be a process of averaging foveal input across sequential fixations (Ji, Chen, & Fu, 2013; Jung, Bulthoff, Thornton, Lee, & Armann, 2013). To test directly whether foveating objects is necessary, we measured observers' sensitivity to average facial emotion in the absence of foveal input. Subjects viewed arrays of 24 faces, either in the presence or absence of a gaze-contingent foveal occluder, and adjusted a test face to match the average expression of the array. We found no difference in accuracy between the occluded and non-occluded conditions, demonstrating that foveal input is not required for ensemble perception. Unsurprisingly, without foveal input, subjects spent significantly less time directly fixating faces, but this did not translate into any difference in sensitivity to ensemble expression. Next, we varied the number of faces visible from the set to test whether subjects average multiple faces from the crowd. In both conditions, subjects' performance improved as more faces were presented, indicating that subjects integrated information from multiple faces in the display regardless of whether they had access to foveal information. Our results demonstrate that ensemble perception can be a covert process, not requiring access to direct foveal information. PMID- 26360157 TI - Selective Inactivation of Resistant Gram-Positive Pathogens with a Light-Driven Hybrid Nanomaterial. AB - Herein, we present a straightforward strategy to disperse highly insoluble photosensitizers in aqueous environments, without major synthetic efforts and keeping their photosensitizing abilities unaffected. A layered nanoclay was employed to adsorb and to solubilize a highly efficient yet hydrophobic Si(IV) phthalocyaninate in water. The aggregation of the photoactive dye was correlated with its photophysical properties, particularly with the ability to produce highly cytotoxic singlet oxygen. Moreover, the resulting hybrid nanomaterial is able to selectively photoinactivate Gram-positive pathogens, due to local interactions between the bacterial membranes and the negatively charged nanodiscs. Nanotoxicity assays confirmed its innocuousness toward eukaryotic cells, showing that it constitutes a new class of "phototriggered magic bullet" for the inactivation of pathogens in phototherapy, as well as in the development of coatings for self-disinfecting surfaces. PMID- 26360156 TI - Distinct cognitive mechanisms involved in the processing of single objects and object ensembles. AB - Behavioral research has demonstrated that the shape and texture of single objects can be processed independently. Similarly, neuroimaging results have shown that an object's shape and texture are processed in distinct brain regions with shape in the lateral occipital area and texture in parahippocampal cortex. Meanwhile, objects are not always seen in isolation and are often grouped together as an ensemble. We recently showed that the processing of ensembles also involves parahippocampal cortex and that the shape and texture of ensemble elements are processed together within this region. These neural data suggest that the independence seen between shape and texture in single-object perception would not be observed in object-ensemble perception. Here we tested this prediction by examining whether observers could attend to the shape of ensemble elements while ignoring changes in an unattended texture feature and vice versa. Across six behavioral experiments, we replicated previous findings of independence between shape and texture in single-object perception. In contrast, we observed that changes in an unattended ensemble feature negatively impacted the processing of an attended ensemble feature only when ensemble features were attended globally. When they were attended locally, thereby making ensemble processing similar to single-object processing, interference was abolished. Overall, these findings confirm previous neuroimaging results and suggest that distinct cognitive mechanisms may be involved in single-object and object-ensemble perception. Additionally, they show that the scope of visual attention plays a critical role in determining which type of object processing (ensemble or single object) is engaged by the visual system. PMID- 26360158 TI - Get ready for revalidation. PMID- 26360159 TI - New service models proposed for cardiac disease services. PMID- 26360161 TI - Children with complex infections can receive antibiotics at home. PMID- 26360162 TI - Care for babies with failing health to be reviewed nationally. PMID- 26360163 TI - Children want to see their school nurses wearing uniforms, conference told. PMID- 26360164 TI - Alert system flags up risk of abuse during registration process. PMID- 26360165 TI - National children's care report shows disparities in treatment. PMID- 26360166 TI - Giving children the best start in life. PMID- 26360171 TI - Research essentials. PMID- 26360172 TI - Nurses should be familiar with vital signs for different age groups. PMID- 26360176 TI - Starting out--An intensive experience. PMID- 26360177 TI - How to demonstrate fitness to practise. PMID- 26360178 TI - Overweight and obesity interventions and prevention strategies. AB - AIM: To determine what secondary schoolchildren in Jordan want from overweight and obesity intervention strategies and prevention programmes. METHOD: A school based, cross-sectional study using a quantitative design was carried out during October 2014. The participants were secondary schoolchildren in grades 11 and 12. Data were analysed using SPSS program version 17. Percentages, standard deviations and means were computed. FINDINGS: The main suggestions were for programmes at school, during school hours (n=962, 85.4%), followed by one that involved family and friends (n=951, 84.5%), and a programme at a convenient time free of charge (n=919, 81.6%). The students also suggested many strategies to tackle overweight and obesity, such as: taking more physical exercise (n=925, 82.1%), increasing consumption of more fruit and vegetables (n=712, 63.2%) eating less fast food (n=689, 61.2%). CONCLUSION: Schools, families, health providers and community organisations should encourage students to adopt healthy lifestyles, and facilitate their selection and participation in health programmes. PMID- 26360179 TI - Parents' experiences of hope following a child's brain injury. AB - AIM: To explore the lived experiences of parents caring for their child following a severe to moderate acquired brain injury (ABI). METHODS: A Heideggerian phenomenological approach was used and the research set within the naturalistic paradigm. Eight parents were identified using purposive sampling. Each parent was interviewed on a one-to-one basis using semi-structured interviews. The interviews were typed up verbatim and the data were analysed using thematic analysis. FINDINGS: Every parent acknowledged the need to maintain hope. The other themes identified were: the effects on the child post ABI, the need for accurate information, emotional support, effects on the family, fear of death, transition, family accommodation and funding. CONCLUSION: Following a childhood brain injury it is important that parents can maintain a sense of hope and receive emotional support and accurate information. Staff could use these research findings to increase their awareness and inform their own practice. PMID- 26360180 TI - An overview of the nursing issues involved in caring for a child with adrenal insufficiency. AB - Adrenal insufficiency is an endocrine condition defined as the inadequate production or action of glucocorticoids, principally a steroid hormone called cortisol. While rare in childhood, it carries the risk of adrenal crisis in the event of a child becoming unwell as a result of intercurrent illness, injury or surgery. Children's nurses must be vigilant in caring for a child with adrenal insufficiency and have a clear understanding and awareness of the principles of emergency management at home and in hospital. PMID- 26360181 TI - A Systematic Review of Telehealth in Palliative Care: Caregiver Outcomes. AB - OBJECTIVE: Telehealth interventions have proven efficacy in healthcare, but little is known about the results of such interventions in palliative care. We conducted a systematic review to evaluate caregiver outcomes related to palliative telehealth interventions. MATERIALS AND METHODS: We searched multiple databases for articles published between January 2003 and January 2015 related to telehealth in palliative care. Two hundred twenty-one articles were considered; nine of these met study inclusion criteria. Data on study design, population, interventions, methods, outcomes, conclusions, and methodological quality were extracted and evaluated by three investigators. RESULTS: Of the nine studies, five measured caregiver quality of life, three measured caregiver anxiety, and two measured caregiver burden. All the studies measuring caregiver quality of life showed no significant difference after telehealth interventions. The caregiver anxiety score decreased after the intervention in two studies, and one study reported significantly reduced caregiver burden. Although feasibility of or caregiver satisfaction with the telehealth intervention was not the focus of this review, most studies reported such findings. Of the nine studies, the majority were rated as having moderate quality using the Cochrane Collaboration's tool for assessing risk of bias. CONCLUSIONS: This systematic review suggests there is evidence of overall satisfaction in caregivers who undergo a telehealth intervention, but outcomes reported were often not substantial. Methodological flaws and small sample sizes negatively affected study quality. More rigorous research to test and evaluate such palliative interventions is needed. PMID- 26360182 TI - A Metal-Nitride Nanowire Dual-Photoelectrode Device for Unassisted Solar-to Hydrogen Conversion under Parallel Illumination. AB - A dual-photoelectrode device, consisting of a photoanode and photocathode with complementary energy bandgaps, has long been perceived as an ideal scheme for achieving high efficiency, unassisted solar-driven water splitting. Previously reported 2-photon tandem devices, however, generally exhibit an extremely low efficiency (<0.1%), which has been largely limited by the incompatibility between the two photoelectrode materials. Here we show that the use of metal-nitride nanowire photoelectrodes, together with the scheme of parallel illumination by splitting the solar spectrum spatially and spectrally, can break the efficiency bottleneck of conventional 2-photon tandem devices. We have first investigated a dual-photoelectrode device consisting of a GaN nanowire photoanode and an InGaN nanowire photocathode, which exhibited an open circuit potential of 1.3 V and nearly 20-fold enhancement in the power conversion efficiency under visible light illumination (400-600 nm), compared to the individual photoelectrodes in 1 mol/L HBr. We have further demonstrated a dual-photoelectrode device consisting of parallel-connected metal-nitride nanowire photoanodes and a Si/InGaN nanowire photocathode, which can perform unassisted, direct solar-to-hydrogen conversion. A power conversion efficiency of 2% was measured under AM1.5G 1 sun illumination. PMID- 26360183 TI - Characterization of intact protein conjugates and biopharmaceuticals using ion exchange chromatography with online detection by native electrospray ionization mass spectrometry and top-down tandem mass spectrometry. AB - Characterization of biopharmaceutical products is a challenging task, which needs to be carried out at several different levels (including both primary structure and conformation). An additional difficulty frequently arises due to the structural heterogeneity inherent to many protein-based therapeutics (e.g., extensive glycosylation or "designer" modifications such as chemical conjugation) or introduced postproduction as a result of stress (e.g., oxidation and deamidation). A combination of ion-exchange chromatography (IXC) with online detection by native electrospray ionization mass spectrometry (ESI MS) allows characterization of complex and heterogeneous therapeutic proteins and protein conjugates to be accomplished at a variety of levels without compromising their conformational integrity. The IXC/ESI MS measurements allow protein conjugates to be profiled by analyzing conjugation stoichiometry and the presence of multiple positional isomers, as well as to establish the effect of chemical modifications on the conformational integrity of each species. While mass profiling alone is not sufficient for identification of nonenzymatic post-translational modifications (PTMs) that result in a very small mass change of the eluting species (e.g., deamidation), this task can be completed using online top-down structural analysis, as demonstrated using stressed interferon-beta as an example. The wealth of information that can be provided by IXC/native ESI MS and tandem mass spectrometry (MS/MS) on protein-based therapeutics will undoubtedly make it a very valuable addition to the experimental toolbox of biopharmaceutical analysis. PMID- 26360185 TI - CE: Integrative Care: The Evolving Landscape in American Hospitals. AB - OVERVIEW: As the use of complementary and alternative medicine-CAM-has surged in popularity in the United States, many hospitals have begun integrating complementary services and therapies to augment conventional medical care. In this article, the first in a five-part series that will examine various aspects of holistic nursing and forms of complementary care currently in use, the authors provide an overview of some of the integrative care initiatives being introduced in hospitals throughout the United States and report on findings from a survey they conducted of nursing leaders at hospitals that have implemented integrative care programs. PMID- 26360186 TI - CE: Catheter Ablation of Atrial Fibrillation. AB - OVERVIEW: Catheter ablation of atrial fibrillation is a complex procedure. Although complications are rare and their incidence is decreasing, early recognition and appropriate nursing care can prevent an adverse event from spiraling into a major complication. A thorough understanding of complications associated with the ablation of atrial fibrillation and prompt recognition when they occur will help nurses to minimize the substantial morbidity, mortality, and hospital costs associated with them. This article gives an overview of the procedure, its possible complications, and best practices for nursing care. PMID- 26360187 TI - Stick-slip behavior identified in helium cluster growth in the subsurface of tungsten: effects of cluster depth. AB - We have performed a molecular dynamics study on the growth of helium (He) clusters in the subsurface of tungsten (W) (1 0 0) at 300 K, focusing on the role of cluster depth. Irregular 'stick-slip' behavior exhibited during the evolution of the He cluster growth is identified, which is due to the combined effects of the continuous cluster growth and the loop punching induced pressure relief. We demonstrate that the He cluster grows via trap-mutation and loop punching mechanisms. Initially, the self-interstitial atom SIA clusters are almost always attached to the He cluster; while they are instantly emitted to the surface once a critical cluster pressure is reached. The repetition of this process results in the He cluster approaching the surface via a 'stop-and-go' manner and the formation of surface adatom islands (surface roughening), ultimately leading to cluster bursting and He escape. We reveal that, for the Nth loop punching event, the critical size of the He cluster to trigger loop punching and the size of the emitted SIA clusters are correspondingly increased with the increasing initial cluster depth. We tentatively attribute the observed depth effects to the lower formation energies of Frenkel pairs and the greatly reduced barriers for loop punching in the stress field of the W subsurface. In addition, some intriguing features emerge, such as the morphological transformation of the He cluster from 'platelet-like' to spherical, to ellipsoidal with a 'bullet-like' tip, and finally to a 'bottle-like' shape after cluster rupture. PMID- 26360188 TI - Human factors engineering approaches to patient identification armband design. AB - The task of patient identification is performed many times each day by nurses and other members of the care team. Armbands are used for both direct verification and barcode scanning during patient identification. Armbands and information layout are critical to reducing patient identification errors and dangerous workarounds. We report the effort at two large, integrated healthcare systems that employed human factors engineering approaches to the information layout design of new patient identification armbands. The different methods used illustrate potential pathways to obtain standardized armbands across healthcare systems that incorporate human factors principles. By extension, how the designs have been adopted provides examples of how to incorporate human factors engineering into key clinical processes. PMID- 26360189 TI - Normative static grip strength of population of Turkey, effects of various factors and a comparison with international norms. AB - Normative data are of importance in ergonomics and clinical settings. Applying normative data internationally is questionable. To this end, this study aimed to establish gender- and age-specific reference values for static (isometric) hand grip strength of normal population of Turkey with special regard to occupational demand, and compare them with the international norms. The secondary aims were to investigate the effects of gender, age-group, weight-group, job-group, hand and several anthropometric variables on static grip strength. A sample of 211 (128 male and 83 female) volunteers aged between 18 and 69 with various occupations participated in the study. Grip strength data were collected using a Jamar dynamometer with standard testing position, protocol and instructions. The mean and std deviation of maximum voluntary static grip strength values (in N) for dominant and non-dominant hands respectively were 455.2 +/- 73.6 and 441.5 +/- 72.6 for males, and 258 +/- 46.1 and 246.2 +/- 49.1 for females. The mean female strength was about 57% of the mean male strength value for both dominant and non dominant hands. There was a curvilinear relationship of grip strength to age, significant differences between genders, hands, and some age-groups, and a correlation to height, body-mass, BMI and hand dimensions depending on the gender. The comparisons with the norms of other world populations indicate that there are cross-national grip strength variations among some nations but not all. PMID- 26360190 TI - Analysis of foot clearance in firefighters during ascent and descent of stairs. AB - Slips, trips, and falls are a leading cause of injury to firefighters with many injuries occurring while traversing stairs, possibly exaggerated by acute fatigue from firefighting activities and/or asymmetric load carriage. This study examined the effects that fatigue, induced by simulated firefighting activities, and hose load carriage have on foot clearance while traversing stairs. Landing and passing foot clearances for each stair during ascent and descent of a short staircase were investigated. Clearances decreased significantly (p < 0.05) post-exercise for nine of 12 ascent parameters and increased for two of eight descent parameters. Load carriage resulted in significantly decreased (p < 0.05) clearance over three ascent parameters, and one increase during descent. Decreased clearances during ascent caused by fatigue or load carriage may result in an increased trip risk. Increased clearances during descent may suggest use of a compensation strategy to ensure stair clearance or an increased risk of over stepping during descent. PMID- 26360191 TI - Two-handed grip on a mobile phone affords greater thumb motor performance, decreased variability, and a more extended thumb posture than a one-handed grip. AB - Holding a mobile computing device with two hands may affect thumb motor performance, joint postures, and device stability compared to holding the device and tapping the touchscreen with the thumb of the holding hand. We tested the hypotheses that holding a touchscreen mobile phone with two hands lead to increased thumb motor performance, different thumb postures, and decreased device movement relative to using one hand. Ten right-handed participants completed reciprocal thumb tapping tasks between emulated keys on a smartphone in either a one- (portrait) or two-handed (landscape) grip configuration. Effective index of performance measured from Fitts' Law was 9% greater (p < 0.001), movement time 7% faster (p < 0.001), and taps were 4% more precise (p < 0.016) for the two-handed grip. Tapping with a two-handed grip involved significantly different wrist and thumb postures than a one-handed grip. Variability of the computing device's movement was 36-63% lower for the two-handed grip compared to the one-handed grip condition (p < 0.001). The support for our hypotheses suggests that a two-handed grip results in increased performance and more extended wrist and thumb postures than a single-handed grip. Device designs that allow two-handed grips may afford increased performance relative to a one-handed grip. PMID- 26360192 TI - Integrating user centered design, universal design and goal, operation, method and selection rules to improve the usability of DAISY player for persons with visual impairments. AB - The Digital Accessible Information SYstem (DAISY) player is an assistive reading tool developed for use by persons with visual impairments. Certain problems have persisted in the operating procedure and interface of DAISY players, especially for their Chinese users. Therefore, the aim of this study was to redesign the DAISY player with increased usability features for use by native Chinese speakers. First, a User Centered Design (UCD) process was employed to analyze the development of the prototype. Next, operation procedures were reorganized according to GOMS (Goals, Operators, Methods, and Selection rules) methodology. Then the user interface was redesigned according to specific Universal Design (UD) principles. Following these revisions, an experiment involving four scenarios was conducted to compare the new prototype to other players, and it was tested by twelve visually impaired participants. Results indicate the prototype had the quickest operating times, the fewest number of operating errors, and the lowest mental workloads of all the compared players, significantly enhancing the prototype's usability. These findings have allowed us to generate suggestions for developing the next generation of DAISY players for people, especially for Chinese audience. PMID- 26360193 TI - Effects of culture (China vs. US) and task on perceived hazard: Evidence from product ratings, label ratings, and product to label matching. AB - In the current study, 44 Chinese and 40 US college students rated their perceived hazard in response to warning labels and products and attempted to match products with warning labels communicating the same level of hazard. Chinese participants tended to provide lower ratings of hazard in response to labels, but hazard perceived in response to products did not significantly differ as a function of culture. When asked to match a product with a warning label, Chinese participants' hazard perceptions appeared to be better calibrated, than did US participants', across products and labels. The results are interpreted in terms of constructivist theory which suggests that risk perceptions vary depending on the "frame of mind" evoked by the environment/context. Designers of warnings must be sensitive to the fact that product users' cognitive representations develop within a culture and that risk perceptions will vary based on the context in which they are derived. PMID- 26360194 TI - Lower limb flexion posture relates to energy absorption during drop landings with soldier-relevant body borne loads. AB - Fifteen military personnel performed 30-cm drop landings to quantify how body borne load (light, ~6 kg, medium, ~20 kg, and heavy, ~40 kg) impacts lower limb kinematics and knee joint energy absorption during landing, and determine whether greater lower limb flexion increases energy absorption while landing with load. Participants decreased peak hip (P = 0.002), and knee flexion (P = 0.007) posture, but did not increase hip (P = 0.796), knee (P = 0.427) or ankle (P = 0.161) energy absorption, despite exhibiting greater peak hip (P = 0.003) and knee (P = 0.001) flexion, and ankle (P = 0.003) dorsiflexion angular impulse when landing with additional load. Yet, when landing with the light and medium loads, greater hip (R(2) = 0.500, P = 0.003 and R(2) = 0.314, P = 0.030) and knee (R(2) = 0.431, P = 0.008 and R(2) = 0.342, P = 0.022) flexion posture predicted larger knee joint energy absorption. Thus, military training that promotes hip and knee flexion, and subsequently greater energy absorption during landing, may potentially reduce risk of musculoskeletal injury and optimize soldier performance. PMID- 26360195 TI - Factors affecting the risk of developing lower back musculoskeletal disorders (MSDs) in experienced and inexperienced rodworkers. AB - Injury and dropout rates during rodwork training appear to reflect difficulties encountered by apprentices adapting to increased physical demands of tying on slab, one of the rodworking tasks with the highest injury risk. Because experience influences work strategies, and consequently the risk of developing musculoskeletal disorders (MSDs), this study aimed to identify differences in work practices associated with tying rebar on slab, potentially relevant to back MSD development, in experienced and inexperienced rodworkers. Fourteen male rodworkers were recruited from either experienced (>2 years experience post apprenticeship), or inexperienced (<6 months experience) groups. Both tied an area with rebar laid on the ground. Trunk flexion/extension angles were measured. L4/L5 moments were estimated from T9 Erector Spinae EMG. Experienced workers were found to spend longer periods of time in trunk flexed postures, with lower peak L4/L5 moments. Our findings revealed practices associated with each group might have different implications on back health. PMID- 26360196 TI - Observed use of voluntary controls to reduce physical exposures among sheet metal workers of the mechanical trade. AB - INTRODUCTION: Little is known about the transfer into the workplace of interventions designed to reduce the physical demands of sheet metal workers. METHODS: We reviewed videos from a case series of 15 sheet metal worksite assessments performed in 2007-2009 to score postures and physical loads, and to observe the use of recommended interventions to reduce physical exposures in sheet metal activities made by a NIOSH stakeholder meeting in 2002. RESULTS: Workers showed consistent use of material handling devices, but we observed few uses of recommended interventions to reduce exposures during overhead work. Workers spent large proportions of time in awkward shoulder elevation and low back rotation postures. CONCLUSIONS: In addition to the development of new technologies and system designs, increased adoption of existing tools and practices could reduce time spent in awkward postures and other risks for musculoskeletal disorders in sheet metal work. PMID- 26360197 TI - Tallman lettering as a strategy for differentiation in look-alike, sound-alike drug names: the role of familiarity in differentiating drug doppelgangers. AB - Tallman lettering, capitalizing the dissimilar portions of easily confused drug names, is one strategy for reducing medication errors. We assessed the efficacy of Tallman lettering in a visually complex environment using a change detection method with healthcare providers and laypeople. In addition, the effect of familiarity with the drug name was assessed using a subset of responses collected from healthcare providers. Both healthcare providers and laypeople detected changes in confusable pairs of drug names more often (P < 0.0001) and more quickly (P < 0.05) when changes were presented in Tallman lettering, though the benefits were more pronounced for healthcare providers (p < 0.05). Familiarity with both drug names in a confusable pair mitigated the benefit of Tallman lettering. Results are discussed in terms of bottom-up and top-down attentional systems for processing of information in the context of the varied healthcare environments. PMID- 26360198 TI - Predicting physiological capacity of human load carriage - a review. AB - This review article aims to evaluate a proposed maximum acceptable work duration model for load carriage tasks. It is contended that this concept has particular relevance to physically demanding occupations such as military and firefighting. Personnel in these occupations are often required to perform very physically demanding tasks, over varying time periods, often involving load carriage. Previous research has investigated concepts related to physiological workload limits in occupational settings (e.g. industrial). Evidence suggests however, that existing (unloaded) workload guidelines are not appropriate for load carriage tasks. The utility of this model warrants further work to enable prediction of load carriage durations across a range of functional workloads for physically demanding occupations. If the maximum duration for which personnel can physiologically sustain a load carriage task could be accurately predicted, commanders and supervisors could better plan for and manage tasks to ensure operational imperatives were met whilst minimising health risks for their workers. PMID- 26360199 TI - Effects of mental workload on physiological and subjective responses during traffic density monitoring: A field study. AB - This study evaluated operators' mental workload while monitoring traffic density in a city traffic control center. To determine the mental workload, physiological signals (ECG, EMG) were recorded and the NASA-Task Load Index (TLX) was administered for 16 operators. The results showed that the operators experienced a larger mental workload during high traffic density than during low traffic density. The traffic control center stressors caused changes in heart rate variability features and EMG amplitude, although the average workload score was significantly higher in HTD conditions than in LTD conditions. The findings indicated that increasing traffic congestion had a significant effect on HR, RMSSD, SDNN, LF/HF ratio, and EMG amplitude. The results suggested that when operators' workload increases, their mental fatigue and stress level increase and their mental health deteriorate. Therefore, it maybe necessary to implement an ergonomic program to manage mental health. Furthermore, by evaluating mental workload, the traffic control center director can organize the center's traffic congestion operators to sustain the appropriate mental workload and improve traffic control management. PMID- 26360200 TI - A longitudinal investigation of work environment stressors on the performance and wellbeing of office workers. AB - This study uses a longitudinal within-subjects design to investigate the effects of inadequate Indoor Environmental Quality (IEQ) on work performance and wellbeing in a sample of 114 office workers over a period of 8 months. Participants completed a total of 2261 online surveys measuring perceived thermal comfort, lighting comfort and noise annoyance, measures of work performance, and individual state factors underlying performance and wellbeing. Characterising inadequate aspects of IEQ as environmental stressors, these stress factors can significantly reduce self-reported work performance and objectively measured cognitive performance by between 2.4% and 5.8% in most situations, and by up to 14.8% in rare cases. Environmental stressors act indirectly on work performance by reducing state variables, motivation, tiredness, and distractibility, which support high-functioning work performance. Exposure to environmental stress appears to erode individuals' resilience, or ability to cope with additional task demands. These results indicate that environmental stress reduces not only the cognitive capacity for work, but the rate of work (i.e. by reducing motivation). Increasing the number of individual stress factors is associated with a near linear reduction in work performance indicating that environmental stress factors are additive, not multiplicative. Environmental stressors reduce occupant wellbeing (mood, headaches, and feeling 'off') causing indirect reductions in work performance. Improving IEQ will likely produce small but pervasive increases in productivity. PMID- 26360201 TI - The science behind codes and standards for safe pedestrian walkways: lighting and visual cues. AB - BACKGROUND: Walkway codes and standards are created through consensus by committees based on a number of factors, including historical precedence, common practice, cost, and, sometimes, empirical data. The authors maintain that codes and standards that can have an impact on human safety and welfare should give consideration in their formulation to the results of pertinent scientific research. PURPOSE: This article extends a companion one in examining many elements of common walkway codes and standards related specifically to lighting, warnings and markings. It indicates which elements are based on or supported by empirical data; and which elements could benefit from additional scientific research. PRACTICAL APPLICATIONS: This article identifies areas in which additional research leading toward scientific based codes and standards may be beneficial in enhancing the safety of pedestrian walkway surfaces. PMID- 26360202 TI - Reductions in self-reported stress and anticipatory heart rate with the use of a semi-automated parallel parking system. AB - Drivers' reactions to a semi-autonomous technology for assisted parallel parking system were evaluated in a field experiment. A sample of 42 drivers balanced by gender and across three age groups (20-29, 40-49, 60-69) were given a comprehensive briefing, saw the technology demonstrated, practiced parallel parking 3 times each with and without the assistive technology, and then were assessed on an additional 3 parking events each with and without the technology. Anticipatory stress, as measured by heart rate, was significantly lower when drivers approached a parking space knowing that they would be using the assistive technology as opposed to manually parking. Self-reported stress levels following assisted parks were also lower. Thus, both subjective and objective data support the position that the assistive technology reduced stress levels in drivers who were given detailed training. It was observed that drivers decreased their use of turn signals when using the semi-autonomous technology, raising a caution concerning unintended lapses in safe driving behaviors that may occur when assistive technologies are used. PMID- 26360203 TI - Overweight, obesity and work functioning: the role of working-time arrangements. AB - BACKGROUND: Obesity is associated with productivity loss, but little is known about how obese workers function at work and also the role of working-time arrangements on this association is lacking. Therefore, the aim of this study was to examine the association of overweight and obesity with work functioning (WF), and to determine whether the associations differ between workers with different working-time arrangements. METHODS: A cross-sectional study was conducted within the sampling frame of the 'Shift Your Work' study that examined the effect of irregular working-times in relation to health and functioning at work. We included N = 622 Dutch employees, of which N = 384 (62%) were shift-workers, N = 171 (27%) on-call workers and N = 67 (11%) day-workers. Overweight and obesity were defined as BMI 25-30 and >=30, respectively. WF was assessed using the Work Role Functioning Questionnaire. RESULTS: The prevalences of overweight and obesity were 48% and 10% in all workers, 49% and 11% in shift-workers, 45% and 10% in on-call workers, and 49% and 6% in day workers, respectively. In all workers, obesity was associated with lower WF scores for physical demands (adjusted estimate, aB = -5.5). In shift-workers, obesity was associated with lower WF scores for output and physical demands (aB = -8.8 and -6.8, respectively). In day and on-call workers, overweight and obesity were not associated with WF. CONCLUSIONS: Overweight and obesity are highly prevalent in the working population. Obesity might reduce the executive function performance beyond physical limitations, and limit the ability to accomplish tasks successfully, especially in shift workers. PMID- 26360204 TI - Evaluation of the effectiveness of a multi-skill program for training younger drivers on higher cognitive skills. AB - Training programs exist that prove effective at teaching novice drivers to anticipate latent hazards (RAPT), mitigate hazards (ACT) and maintain attention (FOCAL). The current study (a) measures the effectiveness of a novel integrated training program (SAFE-T) that takes only a third as long to complete compared to the three individual training programs and (b) determines if integrating the training of all the three higher cognitive skills would yield results comparable to the existing programs. Three groups were evaluated: SAFE-T, RAPT and Placebo. The results show that the drivers in the SAFE-T-trained group were more likely to anticipate hazards, quicker and more effective at responding to hazards, and more likely to maintain glance durations under a critical threshold of 2 s as compared to drivers in the Placebo-trained group who received a control program that does not actively train on any of the three cognitive skills. Moreover, the results show that the drivers in the SAFE-T trained group were just as likely to anticipate hazards as the drivers in the RAPT trained group. Finally, when compared with prior studies, the drivers in the SAFE-T trained group showed similar effects of attention maintenance training. PMID- 26360205 TI - Ergonomic approach for pillow concept design. AB - Sleep quality is an essential factor to human beings for health. The current paper conducted four studies to provide a suitable pillow for promoting sleep quality. Study 1 investigated the natural positions of 40 subjects during sleep to derive key-points for a pillow design. The results suggested that the supine and lateral positions were alternatively 24 times a night, and the current pillows were too high for the supine position and too low for lateral positions. Study 2 measured body dimensions related to pillow design of 40 subjects to determine pillow sizes. The results suggested that the pillow height were quite different in supine position and lateral position and needed to take into consideration for a pillow design. Study 3 created a pillow design based on the results of above studies. The pillow was a U-form in the front of view in which the pillow height in the middle area was lower for the supine position, and both sides were higher for the lateral positions. Study 4 assessed sleep quality of 6 subjects by using the proposed pillows and the current pillows. The results showed that the newly designed pillow led to significantly higher sleep quality, and the new design received an innovation patent. PMID- 26360206 TI - The application of an industry level participatory ergonomics approach in developing MSD interventions. AB - Participatory ergonomics projects are traditionally applied within one organisation. In this study, a participative approach was applied across the New Zealand meat processing industry, involving multiple organisations and geographical regions. The purpose was to develop interventions to reduce musculoskeletal disorder (MSD) risk. This paper considers the value of an industry level participatory ergonomics approach in achieving this. The main rationale for a participative approach included the need for industry credibility, and to generate MSD interventions that address industry level MSD risk factors. An industry key stakeholder group became the primary vehicle for formal participation. The study resulted in an intervention plan that included the wider work system and industry practices. These interventions were championed across the industry by the key stakeholder group and have extended beyond the life of the study. While this approach helped to meet the study aim, the existence of an industry-supported key stakeholder group and a mandate for the initiative are important prerequisites for success. PMID- 26360207 TI - Lumbar postures, seat interface pressures and discomfort responses to a novel thoracic support for police officers during prolonged simulated driving exposures. AB - A high prevalence of low back pain has been reported among professional drivers, including mobile police officers. The purpose of this investigation was to develop and evaluate a novel thoracic support designed for mobile police officers. Fourteen participants (7 male, 7 female) attended two 120-min driving simulations using a Crown Victoria Interceptor seat and the same seat equipped with a surface mounted thoracic support. Time-varying spine postures, seat pressures and ratings of discomfort were measured. Averaged discomfort values were low (less than 10 mm of a possible 100 mm) for both seating conditions. The postures in the thoracic support condition were more similar to non-occupational driving without occupational equipment than the Crown Victoria seating condition. The reduction in pressure area at the low back with the thoracic support has the potential to reduce discomfort reporting in officers compared to a standard vehicle package. PMID- 26360208 TI - Center of pressure and total force analyses for amputees walking with a backpack load over four surfaces. AB - Understanding how load carriage affects walking is important for people with a lower extremity amputation who may use different strategies to accommodate to the additional weight. Nine unilateral traumatic transtibial amputees (K4-level) walked over four surfaces (level-ground, uneven ground, incline, decline) with and without a 24.5 kg backpack. Center of pressure (COP) and total force were analyzed from F-Scan insole pressure sensor data. COP parameters were greater on the intact limb than on the prosthetic limb, which was likely a compensation for the loss of ankle control. Double support time (DST) was greater when walking with a backpack. Although longer DST is often considered a strategy to enhance stability and/or reduce loading forces, changes in DST were only moderately correlated with changes in peak force. High functioning transtibial amputees were able to accommodate to a standard backpack load and to maintain COP progression, even when walking over different surfaces. PMID- 26360209 TI - Evaluation of jar lid design characteristics by older women with hand use limitations. AB - The study evaluated several lid design characteristics (diameter, height, top shape, side shape, and surface texture) by means of controlled laboratory testing with older women with hand function limitations. A subjective evaluation process was applied to examine main effects and interactions of lid design characteristics on usability, determined by participants' perceptions of effort and discomfort. Results showed that lid height was the most important design characteristic associated with usability. For 42 mm diameter lids, designs perceived as best were ones with taller height, hexagonal top shape, and convex side shape. For 28 mm diameter lids, the best designs were ones with taller height and hexagonal top shape. Additionally, when the smaller lid's side shape was flat, a serrate surface texture provided some advantages, particularly for subjects with more severe hand dysfunction. This information could be used by package designers to improve jar lid usability for a growing sector of consumers. PMID- 26360210 TI - Application of a human factors classification framework for patient safety to identify precursor and contributing factors to adverse clinical incidents in hospital. AB - This study aimed to identify temporal precursor and associated contributing factors for adverse clinical incidents in a hospital setting using the Human Factors Classification Framework (HFCF) for patient safety. A random sample of 498 clinical incidents were reviewed. The framework identified key precursor events (PE), contributing factors (CF) and the prime causes of incidents. Descriptive statistics and correspondence analysis were used to examine incident characteristics. Staff action was the most common type of PE identified. Correspondence analysis for all PEs that involved staff action by error type showed that rule-based errors were strongly related to performing medical or monitoring tasks or the administration of medication. Skill-based errors were strongly related to misdiagnoses. Factors relating to the organisation (66.9%) or the patient (53.2%) were the most commonly identified CFs. The HFCF for patient safety was able to identify patterns of causation for the clinical incidents, highlighting the need for targeted preventive approaches, based on an understanding of how and why incidents occur. PMID- 26360211 TI - Temporal uncertainty analysis of human errors based on interrelationships among multiple factors: a case of Minuteman III missile accident. AB - In traditional approaches of human reliability assessment (HRA), the definition of the error producing conditions (EPCs) and the supporting guidance are such that some of the conditions (especially organizational or managerial conditions) can hardly be included, and thus the analysis is burdened with incomprehensiveness without reflecting the temporal trend of human reliability. A method based on system dynamics (SD), which highlights interrelationships among technical and organizational aspects that may contribute to human errors, is presented to facilitate quantitatively estimating the human error probability (HEP) and its related variables changing over time in a long period. Taking the Minuteman III missile accident in 2008 as a case, the proposed HRA method is applied to assess HEP during missile operations over 50 years by analyzing the interactions among the variables involved in human-related risks; also the critical factors are determined in terms of impact that the variables have on risks in different time periods. It is indicated that both technical and organizational aspects should be focused on to minimize human errors in a long run. PMID- 26360212 TI - The role of organisational support in teleworker wellbeing: a socio-technical systems approach. AB - The prevalence of telework and other forms of mobile working enabled by digital technology is increasing markedly. Following a socio-technical systems approach, this study aims to examine the role of organisational social support and specific support for teleworkers in influencing teleworker wellbeing, the mediating role of social isolation, potentially resulting from a person-environment mismatch in these relationships, and possible differences in these relationships between low intensity and hybrid teleworkers. Teleworkers' (n = 804) perceptions of support and telework outcomes (psychological strain, job satisfaction, and social isolation) were collected using an on-line survey of teleworking employees distributed within 28 New Zealand organisations where knowledge work was undertaken. Organisational social support and teleworker support was associated with increased job satisfaction and reduced psychological strain. Social isolation mediated the relationship between organisational social support and the two outcome variables, and some differences were observed in the structural relationships for hybrid and low-intensity teleworker sub-samples. These findings suggest that providing the necessary organisational and teleworker support is important for enhancing the teleworker-environment fit and thereby ensuring desirable telework outcomes. PMID- 26360213 TI - Dynamic push-pull characteristics at three hand-reach envelopes: applications for the workplace. AB - Pushing and pulling are common tasks in the workplace. Overexertion injuries related to manual pushing and pulling are often observed, and therefore the understanding of work capacity is important for efficient and safe workstation design. The purpose of the present study was to describe workloads obtained during different reach envelopes during a seated push-pull task. Forty-five women performed an isokinetic push-pull sequence at two velocities. Strength, work and agonist/antagonist muscle ratio were calculated for the full range of motion (ROM). We then divided the ROM into three reach envelopes - neutral, medium, and maximum reach. The work capacity for each direction was determined and the reach envelope work data were compared. Push capability was best at medium reach envelope and pulling was best at maximum reach envelope. Push/pull strength ratio was approximately 1. A recommendation was made to avoid strenuous push-pull tasks at neutral reach envelopes. PMID- 26360214 TI - Context-based presets for lighting setup in residential space. AB - This study aims to derive context-based lighting setup presets in residential space by exploring the multilateral relationships among household activities, affects, and lighting setups. Three procedures were involved: First, sixty affective words were evaluated through which seven affect factors were extracted to facilitate the evaluation of colored illumination in the subsequent experiment. Second, in the user study, seven affect factors and thirty household activities were used to evaluate 147 lighting setups extracted from combinations of twelve hues, six illuminance levels, and three purity levels. As a result, twenty lighting setup presets were derived that were not only activity-based, but affect-based as well. Lastly, the twenty presets were prototyped as a set of testbed to further explore potentials and limitations. This study demonstrates that intuitive, context-based presets can help users explore the effects of colored illumination in creating a diverse range of user experiences. PMID- 26360215 TI - Using analytic network process for evaluating mobile text entry methods. AB - This paper highlights a preference evaluation methodology for text entry methods in a touch keyboard smartphone using analytic network process (ANP). Evaluation of text entry methods in literature mainly considers speed and accuracy. This study presents an alternative means for selecting text entry method that considers user preference. A case study was carried out with a group of experts who were asked to develop a selection decision model of five text entry methods. The decision problem is flexible enough to reflect interdependencies of decision elements that are necessary in describing real-life conditions. Results showed that QWERTY method is more preferred than other text entry methods while arrangement of keys is the most preferred criterion in characterizing a sound method. Sensitivity analysis using simulation of normally distributed random numbers under fairly large perturbation reported the foregoing results reliable enough to reflect robust judgment. The main contribution of this paper is the introduction of a multi-criteria decision approach in the preference evaluation of text entry methods. PMID- 26360216 TI - Cultural ergonomics in interactional and experiential design: conceptual framework and case study of the Taiwanese twin cup. AB - Cultural ergonomics is an approach that considers interaction- and experience based variations among cultures. Designers need to develop a better understanding of cultural ergonomics not just to participate in cultural contexts but also to develop interactive experiences for users. Cultural ergonomics extends our understanding of cultural meaning and our ability to utilize such understanding for design and evaluate everyday products. This study aims to combine cultural ergonomics and interactive design to explore human-culture interaction in user experiences. The linnak is a typical Taiwanese aboriginal cultural object. This study examined the cultural meaning and operational interface of the linnak, as well as the scenarios in which it is used in interaction and user experiences. The results produced a cultural ergonomics interface for examining the manner in which designers communicate across cultures as well as the interweaving of design and culture in the design process. PMID- 26360217 TI - Variable Message Signs for road tunnel emergency evacuations. AB - This paper investigates the design of Variable Message Signs (VMS) as a way finding aid for road tunnel emergency evacuations. The use of the Theory of Affordances is suggested to provide recommendations on the design of VMS. A preliminary evaluation of 11 selected VMS systems was performed and 6 of them were further evaluated using an affordance-based within subject stated-preference questionnaire administered to a sample of 62 participants. Results are used to provide recommendations on the characteristics of the VMS systems, such as (1) size of the sign (large or small); (2) use of flashing lights; (3) colour scheme; (4) message coding (i.e., text, pictograms or a combination of them). The best performing VMS features for road tunnel emergency evacuation included the use of larger signs, flashing lights, the combination of emergency exit pictorial symbol in green in one panel and text in amber in the other panel. PMID- 26360218 TI - Assessments of risky driving: a Go/No-Go simulator driving task to evaluate risky decision-making and associated behavioral patterns. AB - This study sought to develop and validate a Go/No-Go Simulator Driving Task (G/NG SDT) to evaluate driver risky decision-making and associated behavioral assessments at a situation-specific level. Eighty-four participants were instructed to complete a route in as short time as possible, but avoiding any violations or crashes. To achieve this aim, they had to decide to go or wait in the dilemma scenes, paired with the baseline scenes in several scenarios. High risk drivers with more Go decisions demonstrated more violations, in both simulator tasks and real road driving, as well as higher scores of Driving Behavior Questionnaire (DBQ) violations and more Balloon Analogue Risk Task (BART) pumps. These high-risk drivers also showed distinguishable behavioral patterns in simulator driving, moderated by the specific driving situations (e.g. scenario and scene). Several behavior assessments were consistently distinguishable in all tested situations, qualified as robust indictors to predict risk-taking in more general driving situations. PMID- 26360219 TI - Age-related differences in dynamic balance control during stair descent and effect of varying step geometry. AB - The incidence of stairway falls and related injuries remains persistently high; however, the risk of stair injuries could be reduced through improved stairway design. The current study investigated dynamic balance control during stair descent and the effects of varying the step geometry. Data were collected from 20 healthy young and 20 older adults as they descended three staircases (riser heights of 7, 7.5 and 8 inches (178, 190 and 203 mm, respectively)). At each riser height, the tread run length was varied between 8 and 14 inches (203 mm and 356 mm) in one-inch (25 mm) increments. Kinematic data provided measures of segmental and whole-body dynamic control. Results demonstrated that older adults had greater lateral tilt of the upper body than young adults, but actually had larger margins of stability than the young in the antero-posterior direction as a result of their slower cadence. Nonetheless, for both age groups, the longer run lengths were found to provide the largest margins of stability. In addition, increase in run length and decrease in riser height tended to reduce forward upper body tilt. These results help to explain the underlying biomechanical factors associated with increased risk of falls and the relationship with step geometry. Considering the importance of stair ambulation in maintaining independence and activity in the community, this study highlights the definite need for safer stair design standards to minimize the risk of falls and increase stair safety across the lifespan. PMID- 26360220 TI - Feedback has a positive effect on cognitive function during total sleep deprivation if there is sufficient time for it to be effectively processed. AB - This study examined whether the provision of feedback and the interval between successive stimuli interact to affect performance on a serial simple reaction time test during sleep deprivation. Sixteen participants (9 female, 7 male, aged 18-27 yr) completed four versions of the 5-min psychomotor vigilance task for a handheld personal digital assistant (PalmPVT) every 2 h during 28 h of sustained wakefulness. The four versions differed in terms of whether or not they provided feedback immediately after each response, and whether the inter-stimulus intervals (ISIs) were long (2-10 s) or short (1-5 s). Cognitive function was assessed using reciprocal response time and percentage of responses that were lapses (i.e., had a response time >= 500 ms). Data were analysed using repeated measures ANOVA with three within-subjects factors: test session, feedback, and ISI. For both measures, the only significant interaction was between feedback and ISI. Cognitive function was enhanced by feedback when the ISIs were long because it provided motivation. Cognitive function was not affected by feedback when the ISIs were short because there was insufficient time to both attend to the feedback and prepare for the subsequent stimulus. PMID- 26360221 TI - The influence of age in usability testing. AB - The effects of age in usability testing were examined in an experiment. Sixty users from two age groups (M = 23.0 yrs, M = 58.1 yrs) operated two technical devices (keyboard-based and touchscreen-based smartphones). In addition to various performance measures (e.g. task completion time, task completion rate), several subjective measures were taken (e.g. perceived usability, affect, and workload). The results showed better performance scores for younger adults than older adults for task completion time. For older adult users there was a mismatch between usability ratings and task completion time but not between usability ratings and task completion rate. Age-related differences in the importance of speed and accuracy in task completion point to the need to consider more strongly the factor user age in usability research and practice. PMID- 26360222 TI - Aircraft passenger comfort experience: underlying factors and differentiation from discomfort. AB - Previous studies defined passengers' comfort based on their concerns during the flight and a set of eight experiential factors such as 'peace of mind', 'physical wellbeing', 'pleasure', etc. One Objective of this paper was to determine whether the factors underlying the passengers' experience of comfort differ from those of discomfort. Another objective was to cross-validate those factors. In the first study, respondents provided written reports of flight comfort and discomfort experiences separately and gave ratings on the impact of the eight factors on each experience. Follow up interviews were also conducted. Significant difference was found between comfort and discomfort ratings for two factors of 'pleasure', denoted by one's concern for stimulation, ambience and exceeded expectations, and 'physical wellbeing' characterized in terms of bodily support and energy. However, there were no significant differences between the comfort and discomfort ratings on the other six factors. The evidence does not support the proposition that passenger comfort and discomfort are underline by different sets of factors. It is therefore suggested that the evaluation of overall passenger comfort experience, as a whole, employ one spectrum ranging from extreme comfort to discomfort. In study two, a pool of comfort descriptors was collected. Those that were less relevant to passenger comfort were eliminated in a number of steps. Factor analysis was used to classify the remaining descriptors, using respondents' ratings on their potential impact on passenger comfort. Seven factors corresponded to the pre-determined passenger comfort factors from previous research, validating those with an exception of 'proxemics' (concerning one's privacy and control over their situation) but it was argued that this is due to the nature of the factor itself, which is context dependent and generally perceived unconsciously. PMID- 26360223 TI - The science behind codes and standards for safe walkways: changes in level, stairways, stair handrails and slip resistance. AB - Walkway codes and standards are often created through consensus by committees based on a number of factors, including historical precedence, common practice, cost, and empirical data. The authors maintain that in the formulation of codes and standards that impact pedestrian safety, the results of pertinent scientific research should be given significant weight. This article examines many elements of common walkway codes and standards related to changes in level, stairways, stair handrails, and slip resistance. It identifies which portions are based on or supported by empirical data; and which could benefit from additional scientific research. This article identifies areas in which additional research, codes, and standards may be beneficial to enhance pedestrian safety. PMID- 26360224 TI - Photograph-based ergonomic evaluations using the Rapid Office Strain Assessment (ROSA). AB - The Rapid Office Strain Assessment (ROSA) was developed to assess musculoskeletal disorder (MSD) risk factors for computer workstations. This study examined the validity and reliability of remotely conducted, photo-based assessments using ROSA. Twenty-three office workstations were assessed on-site by an ergonomist, and 5 photos were obtained. Photo-based assessments were conducted by three ergonomists. The sensitivity and specificity of the photo-based assessors' ability to correctly classify workstations was 79% and 55%, respectively. The moderate specificity associated with false positive errors committed by the assessors could lead to unnecessary costs to the employer. Error between on-site and photo-based final scores was a considerable ~2 points on the 10-point ROSA scale (RMSE = 2.3), with a moderate relationship (rho = 0.33). Interrater reliability ranged from fairly good to excellent (ICC = 0.667-0.856) and was comparable to previous results. Sources of error include the parallax effect, poor estimations of small joint (e.g. hand/wrist) angles, and boundary errors in postural binning. While this method demonstrated potential validity, further improvements should be made with respect to photo-collection and other protocols for remotely-based ROSA assessments. PMID- 26360225 TI - Concentration on performance with P300-based BCI systems: a matter of interface features. AB - People who suffer from severe motor disabilities have difficulties to communicate with others or to interact with their environment using natural, i.e., muscular channels. These limitations can be overcome to some extent by using brain computer interfaces (BCIs), because such systems allow users to communicate on the basis of their brain activity only. Among the several types of BCIs for spelling purposes, those that rely on the P300 event related potential-P300-based spellers-are chosen preferentially due to their high reliability. However, they demand from the user to sustain his/her attention to the desired character over a relatively long period of time. Therefore, the user's capacity to concentrate can affect his/her performance with a P300-based speller. The aim of this study was to test this hypothesis using three different interfaces: one based on the classic P300 speller paradigm, another also based on that speller but including a word predictor, and a third one that was based on the T9 interface developed for mobile phones. User performance was assessed by measuring the time to complete a spelling task and the accuracy of character selection. The d2 test was applied to assess attention and concentration. Sample (N = 14) was divided into two groups basing on of concentration scores. As a result, performance was better with the predictor-enriched interfaces: less time was needed to solve the task and participants made fewer errors (p < .05). There were also significant effects of concentration (p < .05) on performance with the standard P300 speller. In conclusion, the performance of those users with lower concentration level can be improved by providing BCIs with more interactive interfaces. These findings provide substantial evidence in order to highlight the impact of psychological features on BCI performance and should be taken into account for future assistive technology systems. PMID- 26360226 TI - System reliability, performance and trust in adaptable automation. AB - The present study examined the effects of reduced system reliability on operator performance and automation management in an adaptable automation environment. 39 operators were randomly assigned to one of three experimental groups: low (60%), medium (80%), and high (100%) reliability of automation support. The support system provided five incremental levels of automation which operators could freely select according to their needs. After 3 h of training on a simulated process control task (AutoCAMS) in which the automation worked infallibly, operator performance and automation management were measured during a 2.5-h testing session. Trust and workload were also assessed through questionnaires. Results showed that although reduced system reliability resulted in lower levels of trust towards automation, there were no corresponding differences in the operators' reliance on automation. While operators showed overall a noteworthy ability to cope with automation failure, there were, however, decrements in diagnostic speed and prospective memory with lower reliability. PMID- 26360227 TI - Paracentral Acute Middle Maculopathy: What We Knew Then and What We Know Now. PMID- 26360228 TI - Erythromycin oxidation and ERY-resistant Escherichia coli inactivation in urban wastewater by sulfate radical-based oxidation process under UV-C irradiation. AB - This study evaluates the feasibility of UV-C-driven advanced oxidation process induced by sulfate radicals SO4(.)- in degrading erythromycin (ERY) in secondary treated wastewater. The results revealed that 10 mg L(-1) of sodium persulfate (SPS) can result in rapid and complete antibiotic degradation within 90 min of irradiation, while ERY decay exhibited a pseudo-first-order kinetics pattern under the different experimental conditions applied. ERY degradation rate was strongly affected by the chemical composition of the aqueous matrix and it decreased in the order of: ultrapure water (kapp = 0.55 min(-1)) > bottled water (kapp = 0.26 min(-1)) > humic acid solution (kapp = 0.05 min(-1)) > wastewater effluents (kapp = 0.03 min(-1)). Inherent pH conditions (i.e. pH 8) yielded an increased ERY degradation rate, compared to that observed at pH 3 and 5. The contribution of hydroxyl and sulfate radicals (HO. and SO4(.)-) on ERY degradation was found to be ca. 37% and 63%, respectively. Seven transformation products (TPs) were tentatively elucidated during ERY oxidation, with the 14 membered lactone ring of the ERY molecule being intact in all cases. The observed phytotoxicity against the tested plant species can potentially be attributed to the dissolved effluent organic matter (dEfOM) present in wastewater effluents and its associated-oxidation products and not to the TPs generated from the oxidation of ERY. This study evidences the potential use of the UV-C/SPS process in producing a final treated effluent with lower phytotoxicity (<10%) compared to the untreated wastewater. Finally, under the optimum experimental conditions, the UV-C/SPS process resulted in total inactivation of ERY-resistant Escherichia coli within 90 min. PMID- 26360229 TI - A systematic study of multiple minerals precipitation modelling in wastewater treatment. AB - Mineral solids precipitation is important in wastewater treatment. However approaches to minerals precipitation modelling are varied, often empirical, and mostly focused on single precipitate classes. A common approach, applicable to multi-species precipitates, is needed to integrate into existing wastewater treatment models. The present study systematically tested a semi-mechanistic modelling approach, using various experimental platforms with multiple minerals precipitation. Experiments included dynamic titration with addition of sodium hydroxide to synthetic wastewater, and aeration to progressively increase pH and induce precipitation in real piggery digestate and sewage sludge digestate. The model approach consisted of an equilibrium part for aqueous phase reactions and a kinetic part for minerals precipitation. The model was fitted to dissolved calcium, magnesium, total inorganic carbon and phosphate. Results indicated that precipitation was dominated by the mineral struvite, forming together with varied and minor amounts of calcium phosphate and calcium carbonate. The model approach was noted to have the advantage of requiring a minimal number of fitted parameters, so the model was readily identifiable. Kinetic rate coefficients, which were statistically fitted, were generally in the range 0.35-11.6 h(-1) with confidence intervals of 10-80% relative. Confidence regions for the kinetic rate coefficients were often asymmetric with model-data residuals increasing more gradually with larger coefficient values. This suggests that a large kinetic coefficient could be used when actual measured data is lacking for a particular precipitate-matrix combination. Correlation between the kinetic rate coefficients of different minerals was low, indicating that parameter values for individual minerals could be independently fitted (keeping all other model parameters constant). Implementation was therefore relatively flexible, and would be readily expandable to include other minerals. PMID- 26360230 TI - Enhanced desalination performance of membrane capacitive deionization cells by packing the flow chamber with granular activated carbon. AB - A new design of membrane capacitive deionization (MCDI) cell was constructed by packing the cell's flow chamber with granular activated carbon (GAC). The GAC packed-MCDI (GAC-MCDI) delivered higher (1.2-2.5 times) desalination rates than the regular MCDI at all test NaCl concentrations (~ 100-1000 mg/L). The greatest performance enhancement by packed GAC was observed when treating saline water with an initial NaCl concentration of 100 mg/L. Several different GAC materials were tested and they all exhibited similar enhancement effects. Comparatively, packing the MCDI's flow chamber with glass beads (GB; non-conductive) and graphite granules (GG; conductive but with lower specific surface area than GAC) resulted in inferior desalination performance. Electrochemical impedance spectroscopy (EIS) analysis showed that the GAC-MCDI had considerably smaller internal resistance than the regular MCDI (~ 19.2 +/- 1.2 Omega versus ~ 1222 +/- 15 Omega at 100 mg/L NaCl). The packed GAC also decreased the ionic resistance across the flow chamber (~ 1.49 +/- 0.05 Omega versus ~ 1130 +/- 12 Omega at 100 mg/L NaCl). The electric double layer (EDL) formed on the GAC surface was considered to store salt ions during electrosorption, and facilitate the ion transport in the flow chamber because of the higher ion conductivity in the EDLs than in the bulk solution, thereby enhancing the MCDI's desalination rate. PMID- 26360231 TI - Relative importance of plant uptake and plant associated denitrification for removal of nitrogen from mine drainage in sub-arctic wetlands. AB - Reactive nitrogen (N) species released from undetonated ammonium-nitrate based explosives used in mining or other blasting operations are an emerging environmental problem. Wetlands are frequently used to treat N-contaminated water in temperate climate, but knowledge on plant-microbial interactions and treatment potential in sub-arctic wetlands is limited. Here, we compare the relative importance of plant uptake and denitrification among five plant species commonly occurring in sub-arctic wetlands for removal of N in nitrate-rich mine drainage in northern Sweden. Nitrogen uptake and plant associated potential denitrification activity and genetic potential for denitrification based on quantitative PCR of the denitrification genes nirS, nirK, nosZI and nosZII were determined in plants growing both in situ and cultivated in a growth chamber. The growth chamber and in situ studies generated similar results, suggesting high relevance and applicability of results from growth chamber experiments. We identified denitrification as the dominating pathway for N-removal and abundances of denitrification genes were strong indicators of plant associated denitrification activity. The magnitude and direction of the effect differed among the plant species, with the aquatic moss Drepanocladus fluitans showing exceptionally high ratios between denitrification and uptake rates, compared to the other species. However, to acquire realistic estimates of N-removal potential of specific wetlands and their associated plant species, the total plant biomass needs to be considered. The species-specific plant N-uptake and abundance of denitrification genes on the root or plant surfaces were affected by the presence of other plant species, which show that both multi- and inter-trophic interactions are occurring. Future studies on N-removal potential of wetland plant species should consider how to best exploit these interactions in sub arctic wetlands. PMID- 26360232 TI - Comparison of fuel value and combustion characteristics of two different RDF samples. AB - Generation of Municipal Solid Waste (MSW) tends to increase with the growing population and economic development of the society; therefore, establishing environmentally sustainable waste management strategies is crucial. In this sense, waste to energy strategies have come into prominence since they increase the resource efficiency and replace the fossil fuels with renewable energy sources by enabling material and energy recovery instead of landfill disposal of the wastes. Refuse Derived Fuel (RDF), which is an alternative fuel produced from energy-rich Municipal Solid Waste (MSW) materials diverted from landfills, is one of the waste to energy strategies gaining more and more attention. This study aims to investigate the thermal characteristics and co-combustion efficiency of two RDF samples in Turkey. Proximate, ultimate and thermogravimetric analyses (TGA) were conducted on these samples. Furthermore, elemental compositions of ash from RDF samples were determined by X-Ray Fluorescence (XRF) analysis. The RDF samples were combusted alone and co-combusted in mixtures with coal and petroleum coke in a lab scale reactor at certain percentages on energy basis (3%, 5%, 10%, 20% and 30%) where co-combustion processes and efficiencies were investigated. It was found that the calorific values of RDF samples on dry basis were close to that of coal and a little lower compared to petroleum coke used in this study. Furthermore, the analysis indicated that when RDF in the mixture was higher than 10%, the CO concentration in the flue gas increased and so the combustion efficiency decreased; furthermore, the combustion characteristics changed from char combustion to volatile combustion. However, RDF addition to the fuel mixtures decreased the SO2 emission and did not change the NOx profiles. Also, XRF analysis showed that the slagging and fouling potential of RDF combustion was a function of RDF portion in fuel blend. When the RDF was combusted alone, the slagging and fouling indices of its ash were found to be higher than the limit values producing slagging and fouling. PMID- 26360233 TI - Auditory change-related cerebral responses and personality traits. AB - The rapid detection of changes in sensory information is an essential process for survival. Individual humans are thought to have their own intrinsic preattentive responsiveness to sensory changes. Here we sought to determine the relationship between auditory change-related responses and personality traits, using event related potentials. A change-related response peaking at approximately 120 ms (Change-N1) was elicited by an abrupt decrease in sound pressure (10 dB) from the baseline (60 dB) of a continuous sound. Sixty-three healthy volunteers (14 females and 49 males) were recruited and were assessed by the Temperament and Character Inventory (TCI) for personality traits. We investigated the relationship between Change-N1 values (amplitude and latency) and each TCI dimension. The Change-N1 amplitude was positively correlated with harm avoidance scores and negatively correlated with the self-directedness scores, but not with other TCI dimensions. Since these two TCI dimensions are associated with anxiety disorders and depression, it is possible that the change-related response is affected by personality traits, particularly anxiety- or depression-related traits. PMID- 26360234 TI - Women's Attitudes Toward Cervicovaginal Self-Sampling for High-Risk HPV Infection on the US-Mexico Border. AB - OBJECTIVE: The purpose of this study was to assess the acceptability and intention to use cervicovaginal self-sampling for high-risk human papillomavirus infection after receiving an educational intervention among the predominantly Hispanic population residing along the US-Mexico border. METHODS: Women received an educational intervention about cervical cancer prevention through screening with conventional cytology and with self-sampling for high-risk human papillomavirus. After the educational intervention, women performed the self sampling test. Women's attitudes toward the self-sampling test and cervical cytology were assessed and compared. RESULTS: A total of 110 women aged 30 to 65 years completed the study. The mean (SD) age of the population was 48 (9.3) years. Most (87%) self-identified as being Hispanic and half were born in Mexico; 16% had not had cervical cytology done in 3 years. Self-sampling was more acceptable than cervical cytology; mean (SD) acceptability scores were 25.0 (2.9) and 22.7 (3.0), respectively, with the maximum possible score being 28 (p < .001). A large proportion (42.7%) of women preferred both tests equally. We found high intention to use and recommend self-sampling. Contrary to previous studies, there were no differences between cervical cytology and self-sampling regarding women's concerns about performing the test well and the accuracy of the test, which we attribute to the educational intervention. CONCLUSION: The high acceptability of self-sampling after participants received education about the test and the reported intention to use it if made available add to the evidence on the feasibility of integrating self-testing within cervical cancer screening guidelines. PMID- 26360235 TI - Human Papillomavirus-Related Ovarian Metastasis With Endocervical Adenocarcinoma: Report of 2 Cases and Review of Literature. AB - BACKGROUND: Most endocervical adenocarcinomas are associated with human papillomavirus (HPV) infection. Studies suggest that synchronous endocervical and ovarian tumors can contain identical HPV subtypes and that, in this setting, the ovarian tumors likely represent metastases from the endocervical adenocarcinoma rather than 2 independent primaries. However, there are still relatively few reports in the literature. RESULTS: We describe 2 patients with HPV-related endocervical adenocarcinoma or adenocarcinoma in situ who had metastatic ovarian tumors that simulated primary ovarian neoplasms. After total hysterectomy and bilateral salpingo-oophorectomy, patient 1, in her mid-40s, was diagnosed with endocervical adenocarcinoma in situ and patient 2, in her early 50s, was diagnosed with endocervical adenocarcinoma showing early focal stromal invasion. The ovarian tumors in both cases simulated independent borderline mucinous tumors without evidence of surface involvement or spread beyond the ovary. However, in both cases, the cervical and ovarian tumors showed diffuse, strong P16 staining and contained identical high-risk HPV subtypes (subtypes 16 and 18 in patient 1 and subtype 16 in patient 2). Patient 1 was treated with radiation therapy and remains recurrence free 5 years after diagnosis, and patient 2 has recently completed combined modality treatment with radiation therapy and cisplatin chemotherapy and remains recurrence free 10 months after diagnosis. CONCLUSIONS: A high index of suspicion and ancillary testing, including P16 immunostaining and molecular genetic testing for HPV, is required to properly diagnose and subclassify HPV-related endocervical adenocarcinoma metastatic to the ovary. PMID- 26360236 TI - Atopic Dermatitis Is Associated With Cervical High Risk Human Papillomavirus Infection. AB - OBJECTIVE: High-risk human papillomavirus (hrHPV) infection is more likely to persist and cause cervical cancer in immunosuppressed women. Atopic dermatitis, which is known to affect cell-mediated immunity and skin barrier function, is associated with recalcitrant warts; therefore, we hypothesized that women with atopic dermatitis may be more likely to be positive for hrHPV infection and progress to high-grade cervical dysplasia. MATERIALS AND METHODS: A retrospective case-control study of 1,160 women who were either positive or negative for hrHPV in their index cervical cytology. Patient age, race, history of atopic dermatitis, allergic rhinitis, smoking, body mass index, socioeconomic status, marital status, hormone contraceptive use, and 2-year clinical outcomes (follow up hrHPV testing and cervical biopsy results) were recorded. All cases with atopic dermatitis (n = 74) were confirmed by a dermatologist. Analyses were restricted to females with documented clinical follow-up, which yielded 577 hrHPV positive and 583 hrHPV-negative cases for comparison. Associations were examined by t test, chi test, and multivariate logistic regression. RESULTS: Atopic dermatitis was more common in the hrHPV-positive cases (48/577, 8.3%) compared with HPV-negative controls (26/583, 4.5%, p = .007). Multivariate logistic regression analysis revealed an adjusted odds ratio of 3.75 (95% CI = 1.3-10.9, p = .02) after controlling for significant covariates, such as age and marital status. Smoking was not associated with hrHPV infection, persistence, or high grade cervical dysplasia in these cases. CONCLUSIONS: Atopic dermatitis is associated with cervical hrHPV infection in adult women. PMID- 26360237 TI - Comparing results from long and short form versions of the Parkinson's disease questionnaire in a longitudinal study. AB - BACKGROUND: The purpose of this study was to determine the extent to which summary index scores from the short form Parkinson's Disease Questionnaire (PDQ 8) replicate those from the parent form (PDQ-39) in a longitudinal study. METHODS: Longitudinal data gained from the PD-MED trial were examined (n = 1867), to determine the extent the PDQ-8 replicates results from the PDQ-39 at baseline and follow up. The sensitivity to change of the PDQ-8 was also compared with that of the PDQ-39. Finally, results on the two measures were compared with those from the Hoehn and Yahr (HY) clinical staging scale. RESULTS: Results of the Single Index summary score gained from the PDQ-8 were found to closely replicate those gained from the PDQ-39 at each of the three time points. Furthermore at each time point the intraclass correlation coefficient between the two measures was very high (ICC range 0.93-0.96). Similarly, the two measures gave very similar accounts of change (e.g. from baseline to follow up at one year effect sizes were 0.18 for the single index calculated using the PDQ-39, and 0.09 when calculated using the PDQ-8). Similar levels of correlation were found between the two indices when correlated with the HY scale. CONCLUSIONS: The PDQ-8 closely replicates results gained from the PDQ-39 when calculating single indices. In instances where a single summary score of the impact of PD on self-reported quality of life is needed, it is likely the PDQ-8 will provide reliable and accurate information. PMID- 26360238 TI - Non-motor symptoms in patients with adult-onset focal dystonia: Sensory and psychiatric disturbances. AB - Dystonia is characterized by the presence of involuntary muscle contractions that cause abnormal movements and posture. Adult onset focal dystonia include cervical dystonia, blepharospasm, arm dystonia and laryngeal dystonia. Besides motor manifestations, patients with focal dystonia frequently also display non-motor signs and symptoms. In this paper, we review the evidence of sensory and psychiatric disturbances in adult patients with focal dystonia. Clinical studies and neurophysiological investigations consistently show that the sensory system is involved in dystonia. Several studies have also demonstrated that neuropsychiatric disorders, particularly depression and anxiety, are more frequent in patients with focal dystonia, whereas data on obsessive compulsive disorders are more contrasting. PMID- 26360239 TI - Rehabilitation for Parkinson's disease: Current outlook and future challenges. AB - Rehabilitation is considered as an adjuvant to pharmacological and surgical treatments for Parkinson's disease (PD) to maximize functional ability and minimize secondary complications. Originally, approaches were based on empirical experience, but growing evidence suggests that exercise-dependent plasticity constitutes the main mechanism underlying the effects of physiotherapy. Exercise increases synaptic strength and influences neurotransmission, thus potentiating functional circuitry in PD. In addition, exercise is a pivotal element of motor learning. PD patients retain a sufficient capacity of motor learning, though learning rates and performance are reduced in comparison to normal controls. Recent meta-analyses demonstrated that rehabilitation could induce short-lasting, but clinically important benefits, particularly for gait and balance. However, the interventions are largely heterogeneous (stretching, muscle strengthening, balance, postural exercises, occupational therapy, cueing, treadmill training), and there is still no consensus about the optimal approach. Innovative techniques have been recently proposed: virtual reality and exergaming, motor imagery and action observation, robot-assisted physiotherapy and non-conventional therapies (e.g.: dance, martial arts). The rehabilitative program for PD should be "goal based" (targeted to practicing and learning specific activities in the core areas), but a number of practice variables (intensity, specificity, complexity) need to be identified and the program should tailored to the individual patients' characteristics. PMID- 26360240 TI - Screening for fetal growth restriction with universal third trimester ultrasonography in nulliparous women in the Pregnancy Outcome Prediction (POP) study: a prospective cohort study. AB - BACKGROUND: Fetal growth restriction is a major determinant of adverse perinatal outcome. Screening procedures for fetal growth restriction need to identify small babies and then differentiate between those that are healthy and those that are pathologically small. We sought to determine the diagnostic effectiveness of universal ultrasonic fetal biometry in the third trimester as a screening test for small-for-gestational-age (SGA) infants, and whether the risk of morbidity associated with being small differed in the presence or absence of ultrasonic markers of fetal growth restriction. METHODS: The Pregnancy Outcome Prediction (POP) study was a prospective cohort study of nulliparous women with a viable singleton pregnancy at the time of the dating ultrasound scan. Women participating had clinically indicated ultrasonography in the third trimester as per routine clinical care and these results were reported as usual (selective ultrasonography). Additionally, all participants had research ultrasonography, including fetal biometry at 28 and 36 weeks' gestational age. These results were not made available to participants or treating clinicians (universal ultrasonography). We regarded SGA as a birthweight of less than the 10th percentile for gestational age and screen positive for SGA an ultrasonographic estimated fetal weight of less than the 10th percentile for gestational age. Markers of fetal growth restriction included biometric ratios, utero-placental Doppler, and fetal growth velocity. We assessed outcomes for consenting participants who attended research scans and had a livebirth at the Rosie Hospital (Cambridge, UK) after the 28 weeks' research scan. FINDINGS: Between Jan 14, 2008, and July 31, 2012, 4512 women provided written informed consent of whom 3977 (88%) were eligible for analysis. Sensitivity for detection of SGA infants was 20% (95% CI 15-24; 69 of 352 fetuses) for selective ultrasonography and 57% (51-62; 199 of 352 fetuses) for universal ultrasonography (relative sensitivity 2.9, 95% CI 2.4-3.5, p<0.0001). Of the 3977 fetuses, 562 (14.1%) were identified by universal ultrasonography with an estimated fetal weight of less than the 10th percentile and were at an increased risk of neonatal morbidity (relative risk [RR] 1.60, 95% CI 1.22-2.09, p=0.0012). However, estimated fetal weight of less than the 10th percentile was only associated with the risk of neonatal morbidity (pinteraction=0.005) if the fetal abdominal circumference growth velocity was in the lowest decile (RR 3.9, 95% CI 1.9-8.1, p=0.0001). 172 (4%) of 3977 pregnancies had both an estimated fetal weight of less than the 10th percentile and abdominal circumference growth velocity in the lowest decile, and had a relative risk of delivering an SGA infant with neonatal morbidity of 17.6 (9.2 34.0, p<0.0001). INTERPRETATION: Screening of nulliparous women with universal third trimester fetal biometry roughly tripled detection of SGA infants. Combined analysis of fetal biometry and fetal growth velocity identified a subset of SGA fetuses that were at increased risk of neonatal morbidity. FUNDING: National Institute for Health Research, Medical Research Council, Sands, and GE Healthcare. PMID- 26360241 TI - Should serial fetal biometry be used in all pregnancies? PMID- 26360242 TI - Is there adequate evidence to encourage early feeding in patients with acute esophageal variceal bleeding? PMID- 26360243 TI - Freehand technique with the predrilled hole method for ulnar-shortening osteotomy. AB - BACKGROUND: Ulnar shortening is a common and useful method for treating ulnar wrist pain from many causes. Many devices used to perform osteotomy have been introduced in the literature; however, the devices are not universally available. The standard freehand technique is still commonly used in clinical practice; however, it is associated with several complications and is time-consuming. We present a freehand technique for ulnar-shortening osteotomy using a predrilled hole method. METHODS: From 2011 to 2013, we performed the predrilled hole method for ulnar shortening in 18 cases using the six-hole limited-contact dynamic compression plate (LC-DCP) and in two cases using the Acumed six-hole Locking Midshaft Ulna Plate. RESULTS: All patients had uneventful union, and the average operative time was 39.7 minutes (range, 32-50 minutes). The average follow-up period was 21 months (range, 12-30 months). There were no complications except in three patients in the LC-DCP group who complained of implant irritation. Good functional outcomes were achieved with this method. CONCLUSION: Our technique is easy and quick to use and can minimize soft-tissue manipulation. The union rate is high and complications are few. PMID- 26360245 TI - Evidence of Nitrogen Loss from Anaerobic Ammonium Oxidation Coupled with Ferric Iron Reduction in an Intertidal Wetland. AB - Anaerobic ammonium oxidation coupled with nitrite reduction is an important microbial pathway of nitrogen removal in intertidal wetlands. However, little is known about the role of anaerobic ammonium oxidation coupled with ferric iron reduction (termed Feammox) in intertidal nitrogen cycling. In this study, sediment slurry incubation experiments were combined with an isotope-tracing technique to examine the dynamics of Feammox and its association with tidal fluctuations in the intertidal wetland of the Yangtze Estuary. Feammox was detected in the intertidal wetland sediments, with potential rates of 0.24-0.36 mg N kg(-1) d(-1). The Feammox rates in the sediments were generally higher during spring tides than during neap tides. The tidal fluctuations affected the growth of iron-reducing bacteria and reduction of ferric iron, which mediated Feammox activity and the associated nitrogen loss from intertidal wetlands to the atmosphere. An estimated loss of 11.5-18 t N km(-2) year(-1) was linked to Feammox, accounting for approximately 3.1-4.9% of the total external inorganic nitrogen transported into the Yangtze Estuary wetland each year. Overall, the co occurrence of ferric iron reduction and ammonium oxidation suggests that Feammox can act as an ammonium removal mechanism in intertidal wetlands. PMID- 26360244 TI - pH-sensitive nanocarrier based on gold/silver core-shell nanoparticles decorated multi-walled carbon manotubes for tracing drug release in living cells. AB - We fabricate a multifunctional nanocarrier based on multi-walled carbon nanotubes (MWCNTs) decorated with gold/silver core-shell nanoparticles (Au@Ag NPs) and fluorescein isothiocyanate (FITC) for tracking the intracellular drug release process. In the demonstrated nanocarrier, the Au@Ag NPs adsorbed on the surface of MWCNTs were labeled with the pH-dependent SERS reporter 4-Mercaptobenzoic acid (4MBA) for SERS based pH sensing. FITC was conjugated on MWCNTs to provide fluorescence signal for tracing the MWCNTs. Fluorescent doxorubicin (DOX) was used as the model drug which can be loaded onto MWCNTs via pi-pi stacking and released from the MWCNTs under acidic condition. By detecting the SERS spectrum of 4MBA, the pH value around the nanocarrier could be monitored. Besides, by tracing the fluorescence of FITC and DOX, we can also investigate the drug release process in cells. Experimental results show that the proposed nanocarrier retained a well pH-sensitive performance in living cells, and the DOX detached from MWCNTs inside the lysosomes and entered into the cytoplasm with the MWCNTs being left in lysosomes. To further investigate the drug release dynamics, 2-D color-gradient pH mapping were plotted, which were calculated from the SERS spectra of 4MBA. The detailed release process and carrier distribution have been recorded as environmental pH changes during cell endocytosis. Furthermore, we also confirmed that the proposed nanocarrier has a good biocompatibility. It indicates that the designed nanocarrier have a great potential in intraceable drug delivery, cancer cells imaging and pH monitoring. PMID- 26360246 TI - Occluded Cigarette Smoke Exposure Causing Localized Chloracne-Like Comedones. AB - Many environmental acne disorders, including chloracne and oil acne, were previously thought to occur predominantly in occupational settings following polycyclic aromatic hydrocarbon exposure. Cigarette smoke has also been shown to contain a large number of these toxic polycyclic aromatic hydrocarbon components and strictly correlates with noninflammatory acneiform lesion development in postadolescent patients. We report a case of localized open comedones associated with occluded cigarette smoke exposure near the nasal cavity due to infrequently changed gauze following rhinectomy. The dermal uptake of polycyclic aromatic hydrocarbon components in cigarette smoke has the potential to function as a contributing factor in chloracne development. Several of these environmental and noninflammatory acne subtypes may share a common molecular propensity for enhanced comedogenesis originating from aryl hydrocarbon receptor pathway effects in the skin. Additional studies are needed to further elucidate the exact mechanistic pathways through which tobacco smoke impacts the integumentary system. PMID- 26360248 TI - The Effects of Cold Stress on Photosynthesis in Hibiscus Plants. AB - The present work studies the effects of cold on photosynthesis, as well as the involvement in the chilling stress of chlororespiratory enzymes and ferredoxin mediated cyclic electron flow, in illuminated plants of Hibiscus rosa-sinensis. Plants were sensitive to cold stress, as indicated by a reduction in the photochemistry efficiency of PSII and in the capacity for electron transport. However, the susceptibility of leaves to cold may be modified by root temperature. When the stem, but not roots, was chilled, the quantum yield of PSII and the relative electron transport rates were much lower than when the whole plant, root and stem, was chilled at 10 degrees C. Additionally, when the whole plant was cooled, both the activity of electron donation by NADPH and ferredoxin to plastoquinone and the amount of PGR5 polypeptide, an essential component of the cyclic electron flow around PSI, increased, suggesting that in these conditions cyclic electron flow helps protect photosystems. However, when the stem, but not the root, was cooled cyclic electron flow did not increase and PSII was damaged as a result of insufficient dissipation of the excess light energy. In contrast, the chlororespiratory enzymes (NDH complex and PTOX) remained similar to control when the whole plant was cooled, but increased when only the stem was cooled, suggesting the involvement of chlororespiration in the response to chilling stress when other pathways, such as cyclic electron flow around PSI, are insufficient to protect PSII. PMID- 26360247 TI - G2/M Cell Cycle Arrest and Tumor Selective Apoptosis of Acute Leukemia Cells by a Promising Benzophenone Thiosemicarbazone Compound. AB - Anti-mitotic therapies have been considered a hallmark in strategies against abnormally proliferating cells. Focusing on the extensively studied family of thiosemicarbazone (TSC) compounds, we have previously identified 4,4' dimethoxybenzophenone thiosemicarbazone (T44Bf) as a promising pharmacological compound in a panel of human leukemia cell lines (HL60, U937, KG1a and Jurkat). Present findings indicate that T44Bf-mediated antiproliferative effects are associated with a reversible chronic mitotic arrest caused by defects in chromosome alignment, followed by induced programmed cell death. Furthermore, T44Bf selectively induces apoptosis in leukemia cell lines when compared to normal peripheral blood mononuclear cells. The underlying mechanism of action involves the activation of the mitochondria signaling pathway, with loss of mitochondrial membrane potential and sustained phosphorylation of anti-apoptotic protein Bcl-xL as well as increased Bcl-2 (enhanced phosphorylated fraction) and pro-apoptotic protein Bad levels. In addition, ERK signaling pathway activation was found to be a requisite for T44Bf apoptotic activity. Our findings further describe a novel activity for a benzophenone thiosemicarbazone and propose T44Bf as a promising anti-mitotic prototype to develop chemotherapeutic agents to treat acute leukemia malignancies. PMID- 26360250 TI - Correction: Plasma Hsp90 Level as a Marker of Early Acute Lymphoblastic Leukemia Engraftment and Progression in Mice. PMID- 26360249 TI - AQUA Cloning: A Versatile and Simple Enzyme-Free Cloning Approach. AB - Assembly cloning is increasingly replacing conventional restriction enzyme and DNA-ligase-dependent cloning methods for reasons of efficiency and performance. Here, we describe AQUA (advanced quick assembly), a simple and versatile seamless assembly cloning approach. We demonstrate the applicability and versatility of AQUA Cloning in selected proof-of-principle applications including targeted insertion-, deletion- and site-directed point-mutagenesis, and combinatorial cloning. Furthermore, we show the one pot de novo assembly of multiple DNA fragments into a single circular plasmid encoding a complex light- and chemically regulated Boolean A NIMPLY B logic operation. AQUA Cloning harnesses intrinsic in vivo processing of linear DNA fragments with short regions of homology of 16 to 32 bp mediated by Escherichia coli. It does not require any kits, enzymes or preparations of reagents and is the simplest assembly cloning protocol to date. PMID- 26360251 TI - Increased STAT3 phosphorylation on CD27(+) B-cells from common variable immunodeficiency disease patients. AB - Maturation and differentiation of B-cells are driven by T-cells' help through IL 21/STAT3 axis in GC centers or through extrafollicular pathways, in a T independent manner. B-cell differentiation is defective in common variable immunodeficiency disease (CVID) patients. We investigated if IL-21/STAT3 axis alterations could influence B-cell fate. We activated purified CVID B-cells with surrogate T-dependent (anti-CD40), T-independent (TLR-9 ligand) stimuli or through B-cell receptor engagement (anti-IgM) with or without IL-21. IL-21 mediated STAT3 activation was greater on CD27(-) than CD27(+) B-cells depending on the stimulus. IL-21 alone induced STAT3 phosphorylation (pSTAT3) only on CD27( ) B-cells and IL-21 induced higher pSTAT3 levels on CD27(-) than CD27(+) B-cells after anti-IgM or anti-CD40 activation. CVID CD27(+) B-cells showed selective STAT3 hyperphosphorylation after activation with anti-IgM or anti-CD40 alone and anti-IgM, anti-CD40 or ODN combined with IL-21. Increased STAT3 activation during immune responses could result in B-cell differentiation defects in CVID. PMID- 26360254 TI - Transplantation of human spleen into immunodeficient NOD/SCID IL2Rgamma(null) mice generates humanized mice that improve functional B cell development. AB - We previously generated humanized TB34N mice that received human fetal thymus (T), bone tissue (B) and fetal liver-derived (FL)-CD34(+) cells (34) in immunodeficient, NOD/SCID IL2Rgamma(null) (N) mice. Although humanized TB34N mice had excellent hematopoiesis, here, we sought to further improve this model by additional transplantation of human spleen tissue (S) as a secondary hematopoietic tissue (TBS34N). The human spleen grafts were enlarged and differentiated into a similar morphology of adult humans, including follicular lymphoid structures with T- and B-cells. The TBS34N mice mimicked mature human immune system (HIS): mature T- and B-cells and follicular dendritic cells; activated germinal center B-cells expressing CD71, BR3(+) cells, memory B-cells and activation-induced cytidine deaminase(+) B-cells; CD138(+) plasma cells were enriched in the mouse spleen. HBsAg-specific hIgG antibodies were secreted into the sera of all TBS34N mice upon immunization with HBsAg. Taken together, the humanized TBS34N mice improved mature HIS and achieved adaptive antibody responses. PMID- 26360253 TI - High-throughput sequencing reveals an altered T cell repertoire in X-linked agammaglobulinemia. AB - To examine the T cell receptor structure in the absence of B cells, the TCR beta CDR3 was sequenced from DNA of 15 X-linked agammaglobulinemia (XLA) subjects and 18 male controls, using the Illumina HiSeq platform and the ImmunoSEQ analyzer. V gene usage and the V-J combinations, derived from both productive and non productive sequences, were significantly different between XLA samples and controls. Although the CDR3 length was similar for XLA and control samples, the CDR3 region of the XLA T cell receptor contained significantly fewer deletions and insertions in V, D, and J gene segments, differences intrinsic to the V(D)J recombination process and not due to peripheral T cell selection. XLA CDR3s demonstrated fewer charged amino acid residues, more sharing of CDR3 sequences, and almost completely lacked a population of highly modified Vbeta gene segments found in control DNA, suggesting both a skewed and contracted T cell repertoire in XLA. PMID- 26360252 TI - Langerhans cells from women with cervical precancerous lesions become functionally responsive against human papillomavirus after activation with stabilized Poly-I:C. AB - Human papillomavirus (HPV)-mediated suppression of Langerhans cell (LC) function can lead to persistent infection and development of cervical intraepithelial neoplasia (CIN). Women with HPV-induced high-grade CIN2/3 have not mounted an effective immune response against HPV, yet it is unknown if LC-mediated T cell activation from such women is functionally impaired against HPV. We investigated the functional activation of in vitro generated LC and their ability to induce HPV16-specific T cells from CIN2/3 patients after exposure to HPV16 followed by treatment with stabilized Poly-I:C (s-Poly-I:C). LC from patients exposed to HPV16 demonstrated a lack of costimulatory molecule expression, inflammatory cytokine secretion, and chemokine-directed migration. Conversely, s-Poly-I:C caused significant phenotypic and functional activation of HPV16-exposed LC, which resulted in de novo generation of HPV16-specific CD8(+) T cells. Our results highlight that LC of women with a history of persistent HPV infection can present HPV antigens and are capable of inducing an adaptive T cell immune response when given the proper stimulus, suggesting that s-Poly-I:C compounds may be attractive immunomodulators for LC-mediated clearance of persistent HPV infection. PMID- 26360255 TI - Unidirectional Expiratory Valve Method to Assess Maximal Inspiratory Pressure in Individuals without Artificial Airway. AB - INTRODUCTION: Maximal Inspiratory Pressure (MIP) is considered an effective method to estimate strength of inspiratory muscles, but still leads to false positive diagnosis. Although MIP assessment with unidirectional expiratory valve method has been used in patients undergoing mechanical ventilation, no previous studies investigated the application of this method in subjects without artificial airway. OBJECTIVES: This study aimed to compare the MIP values assessed by standard method (MIPsta) and by unidirectional expiratory valve method (MIPuni) in subjects with spontaneous breathing without artificial airway. MIPuni reproducibility was also evaluated. METHODS: This was a crossover design study, and 31 subjects performed MIPsta and MIPuni in a random order. MIPsta measured MIP maintaining negative pressure for at least one second after forceful expiration. MIPuni evaluated MIP using a unidirectional expiratory valve attached to a face mask and was conducted by two evaluators (A and B) at two moments (Tests 1 and 2) to determine interobserver and intraobserver reproducibility of MIP values. Intraclass correlation coefficient (ICC[2,1]) was used to determine intraobserver and interobserver reproducibility. RESULTS: The mean values for MIPuni were 14.3% higher (-117.3 +/- 24.8 cmH2O) than the mean values for MIPsta (-102.5 +/- 23.9 cmH2O) (p<0.001). Interobserver reproducibility assessment showed very high correlation for Test 1 (ICC[2,1] = 0.91), and high correlation for Test 2 (ICC[2,1] = 0.88). The assessment of the intraobserver reproducibility showed high correlation for evaluator A (ICC[2,1] = 0.86) and evaluator B (ICC[2,1] = 0.77). CONCLUSIONS: MIPuni presented higher values when compared with MIPsta and proved to be reproducible in subjects with spontaneous breathing without artificial airway. PMID- 26360256 TI - Cumulative history recorded in the depth distribution of radiocesium in sediments deposited on a sandbar. AB - We collected sediments deposited on a sandbar from the surface to 20 cm in depth in the Abukuma River to clarify the history of radiocesium derived from the Fukushima Daiichi Nuclear Power Plant (FDNPP) accident. We analyzed the (137)Cs concentration in the sediments from size-fractioned samples as well as bulk samples. The depth distribution of (137)Cs showed the highest concentration in the deepest sediment layer (18-20 cm) studied, which indicates that sediments with a lower (137)Cs concentration were transported and deposited on sediments having a higher (137)Cs concentration. At the same time, the depth distribution suggests a decrease in radioactivity in provenance areas of the sediments. Analysis of the size-fractioned sediments indicated that the three sediment layers at 4-6 cm, 16-18 cm and 18-20 cm intervals had similar size distribution of (137)Cs and grain size composition although the concentration levels of (137)Cs were different according to their bulk concentrations. The size distribution of (137)Cs also supported the possibility that the decrease in (137)Cs concentration in bulk sediments above 18 cm is due to a decrease in the level of radioactivity in the catchment area. A comparison of the size distribution of (137)Cs between the sediment layers above and below 18 cm suggested that the (137)Cs concentration in the transported fine sediment particles decreased more with time than the (137)Cs concentration in the coarse particles, reflecting the selective transport of the finer particles. The results of this study demonstrated that sediment layers deposited on a sandbar retained the cumulative history of the fluvial transport of radiocesium after the FDNPP accident. PMID- 26360257 TI - Self-initiated coping with Tourette's syndrome: Effect of tic suppression on QOL. AB - OBJECTIVE: Because of the semi-voluntary nature of tics, patients with Tourette' syndrome (TS) often report self-initiated coping with tics. Our goals were to understand the experiences of self-initiated coping with tics by individuals with TS (e.g., suppression frequency, suppression ability, and side effects of tic suppression), and investigate the effects of tic control on quality of life (QOL). METHOD: One hundred participants with TS (38 children and 62 adults) answered a questionnaire concerning tic control, QOL, and other clinical characteristics. RESULT: Fifty-eight percent of the participants always or frequently tried to suppress tics daily. In contrast, over 90% felt uncomfortable or incomplete when they suppressed tics and needed concentration or extra effort to suppress them. Thirty-four percent could suppress tics for less than one minute and 65% could suppress tics for less than 10min. Higher subjective satisfaction with tic control was positively correlated with life satisfaction and QOL. CONCLUSION: Individuals with TS often attempt self-initiated coping in their daily lives, especially through tic suppression, despite experiencing subjective discomfort and being aware that the duration of tic suppression is often limited. Moreover, it was found that their subjective satisfaction with tic control and effective tic suppression might have a positive influence on their life satisfaction and QOL. Thus, self-initiated coping with tics is vital for improving the QOL of individuals with TS and intervention aimed at enhancing subjective satisfaction with tic control could help manage TS. PMID- 26360258 TI - Changes in Tobacco Smoke Exposure following the Institution of a Smoke-Free Policy in the Boston Housing Authority. AB - INTRODUCTION: To protect residents from tobacco smoke exposure (TSE), the Boston Housing Authority (BHA) prohibited smoking in BHA-owned apartments beginning in 2012. Our goal was to determine if the smoke-free policy reduced TSE for non smoking BHA residents. METHODS: We compared TSE before the smoke-free policy (2012) and one year later among BHA residents as well as residents of the neighboring Cambridge Housing Authority (CHA) where no such policy was in place. Participants were a convenience sample of adult non-smoking BHA and CHA residents cohabitating with only non-smokers. Main outcomes were 7-day airborne nicotine in participants' apartments; residents' saliva cotinine; and residents' self reported TSE. RESULTS: We enrolled 287 confirmed non-smokers (192 BHA, 95 CHA). Seventy-nine percent (229) were assessed at follow-up. At baseline, apartment and resident TSE were high in both housing authorities (detectable airborne nicotine: 46% BHA, 48% CHA; detectable saliva cotinine: 49% BHA, 70% CHA). At follow-up there were significant but similar declines in nicotine in both sites (detectable: -33% BHA, -39% CHA, p = 0.40). Detectable cotinine rose among BHA residents while declining among CHA participants (+17% BHA vs. -13% CHA, p = 0.002). Resident self-reported TSE within and outside of the housing environment decreased similarly for both BHA and CHA residents. CONCLUSIONS: Apartment air nicotine decreased after the introduction of the smoke-free policy, though the decline may not have resulted from the policy. The BHA policy did not result in reduced individual-level TSE. Unmeasured sources of non-residential TSE may have contributed to BHA residents' cotinine levels. PMID- 26360260 TI - The land of the free. PMID- 26360261 TI - Treating smoking in mental health settings. PMID- 26360259 TI - Longitudinal Detection and Persistence of Minority Drug-Resistant Populations and Their Effect on Salvage Therapy. AB - BACKGROUND: Drug-resistant HIV are more prevalent and persist longer than previously demonstrated by bulk sequencing due to the ability to detect low frequency variants. To clarify a clinical benefit to monitoring minority-level drug resistance populations as a guide to select active drugs for salvage therapy, we retrospectively analyzed the dynamics of low-frequency drug-resistant population in antiretroviral (ARV)-exposed drug resistant individuals. MATERIALS AND METHODS: Six HIV-infected individuals treated with ARV for more than five years were analyzed. These individuals had difficulty in controlling viremia, and treatment regimens were switched multiple times guided by standard drug resistance testing using bulk sequencing. To detect minority variant populations with drug resistance, we used a highly sensitive allele-specific PCR (AS-PCR) with detection thresholds of 0.3-2%. According to ARV used in these individuals, we focused on the following seven reverse transcriptase inhibitor-resistant mutations: M41L, K65R, K70R, K103N, Y181C, M184V, and T215F/Y. Results of AS-PCR were compared with bulk sequencing data for concordance and presence of additional mutations. To clarify the genetic relationship between low-frequency and high-frequency populations, AS-PCR amplicon sequences were compared with bulk sequences in phylogenetic analysis. RESULTS: The use of AS-PCR enabled detection of the drug-resistant mutations, M41L, K103N, Y181C, M184V and T215Y, present as low-frequency populations in five of the six individuals. These drug resistant variants persisted for several years without ARV pressure. Phylogenetic analysis indicated that pre-existing K103N and T215I variants had close genetic relationships with high-frequency K103N and T215I observed during treatment. DISCUSSION AND CONCLUSION: Our results demonstrate the long-term persistence of drug-resistant viruses in the absence of drug pressure. The rapid virologic failures with pre-existing mutant viruses detectable by AS-PCR highlight the clinical importance of low-frequency drug-resistant viruses. Thus, our results highlight the usefulness of AS-PCR and support its expanded evaluation in ART clinical management. PMID- 26360262 TI - Bending the curve on psychosis outcomes. PMID- 26360263 TI - Prevention of the psychological consequences of trauma. PMID- 26360264 TI - True parity in North American psychiatry. PMID- 26360265 TI - Information systems for global mental health. PMID- 26360266 TI - OCTET does not prove community treatment orders are ineffective. PMID- 26360267 TI - In defence of OCTET. PMID- 26360268 TI - After the flood: young people's perspectives on transition. PMID- 26360269 TI - Corrections. Depression care management for adults older than 60 years in primary care clinics in urban China: a cluster-randomised trial. PMID- 26360270 TI - Corrections. Experiences of hearing voices: analysis of a novel phenomenological survey. PMID- 26360271 TI - WHO's Global Clinical Practice Network for mental health. PMID- 26360272 TI - Cannabis and psychosis. PMID- 26360273 TI - Cannabis and psychosis. PMID- 26360274 TI - Cannabis and psychosis. PMID- 26360275 TI - Cannabis and psychosis - Authors' reply. PMID- 26360277 TI - Renee Binder. PMID- 26360278 TI - France's forensic psychiatry provision--is it up to scratch? PMID- 26360279 TI - Music and madness: from Kontakte to The Cure. PMID- 26360280 TI - Cutting the body to cure the mind. PMID- 26360281 TI - Bethlem Gallery and Museum of the Mind. PMID- 26360282 TI - Things that go bump in the night. PMID- 26360283 TI - Bespoke smoking cessation for people with severe mental ill health (SCIMITAR): a pilot randomised controlled trial. AB - BACKGROUND: People with severe mental ill health are three times more likely to smoke but typically do not access conventional smoking cessation services, contributing to widening health inequalities and reduced life expectancy. We aimed to pilot an intervention targeted at smokers with severe mental ill health and to test methods of recruitment, randomisation, and follow up before implementing a full trial. METHODS: The Smoking Cessation Intervention for Severe Mental Ill Health Trial (SCIMITAR) is a pilot randomised controlled trial of a smoking cessation strategy designed specifically for people with severe mental ill health, to be delivered by mental health nurses and consisting of behavioural support and drugs, compared with a conventional smoking cessation service (ie, usual care). Adults (aged 18 years or older) with bipolar disorder or schizophrenia, who were current smokers, were recruited from NHS primary care and mental health settings in the UK (York, Scarborough, Hull, and Manchester). Eligible participants were randomly allocated to either usual care (control group) or usual care plus the bespoke smoking cessation strategy (intervention group). Randomisation was done via a central telephone system, with computer generated random numbers. We could not mask participants, family doctors, and researchers to the treatment allocation. Our primary outcome was smoking status at 12 months, verified by carbon monoxide measurements or self-report. Only participants who provided an exhaled CO measurement or self-reported their smoking status at 12 months were included in the primary analysis. The trial is registered at ISRCTN.com, number ISRCTN79497236. FINDINGS: Of 97 people recruited to the pilot study, 51 were randomly allocated to the control group and 46 were assigned to the intervention group. Participants engaged well with the bespoke smoking cessation strategy, but no individuals assigned to usual care accessed NHS smoking cessation services. At 12 months, 35 (69%) controls and 33 (72%) people assigned to the intervention group provided a CO measurement or self reported their smoking status. Smoking cessation was highest among individuals who received the bespoke intervention (12/33 [36%] vs 8/35 [23%]; adjusted odds ratio 2.9, 95% CI 0.8-10.5). INTERPRETATION: We have shown the feasibility of recruiting and randomising people with severe mental ill health in a trial of this nature. The level of engagement with a bespoke smoking cessation strategy was higher than with a conventional approach. The effectiveness and safety of a smoking cessation programme designed particularly for people with severe mental ill health should be tested in a fully powered randomised controlled trial. FUNDING: National Institute of Health Research Health Technology Assessment Programme. PMID- 26360284 TI - D-serine for the treatment of negative symptoms in individuals at clinical high risk of schizophrenia: a pilot, double-blind, placebo-controlled, randomised parallel group mechanistic proof-of-concept trial. AB - BACKGROUND: Antagonists of N-methyl-D-aspartate-type glutamate receptors (NMDAR) induce symptoms that closely resemble those of schizophrenia, including negative symptoms. D-serine is a naturally occurring NMDAR modulator that reverses the effects of NMDAR antagonists in animal models of schizophrenia. D-serine effects have been assessed previously for treatment of established schizophrenia, but not in the early stages of the disorder. We aimed to assess effects of D-serine on negative symptoms in at risk individuals. METHODS: We did a double-blind, placebo controlled, parallel-group randomised clinical trial at four academic US centres. Individuals were eligible for inclusion in the study if they were at clinical high risk of schizophrenia, aged between 13-35 years, had a total score of more than 20 on the Scale of Prodromal Symptoms (SOPS), and had an interest in participation in the clinical trial. Exclusion criteria included a history of suprathreshold psychosis symptoms (ie, no longer qualifying as prodromal) or clinical judgment that the reported symptoms from the SOPS were accounted for better by another disorder (eg, depression). Randomisation was done using a generated list with block sizes of four. Participants were stratified by site, with participants, investigators, and assessors all masked through use of identical looking placebos and centralised drug dispensation to study assignment. D-serine (60 mg/kg) was given orally in divided daily doses for 16 weeks. The primary endpoint was for negative SOPS, measured weekly for the first 6 weeks, then every 2 weeks. Participants who received at least one post-baseline assessment were included in analysis. Serum cytokine concentrations were collected at baseline, midpoint, and endpoint to assess the mechanism of action. Safety outcomes including laboratory assessments were obtained for all individuals. This trial is registered with ClinicalTrials.gov, number NCT0082620. FINDINGS: We enrolled participants between April 2, 2009, and July 23, 2012. 44 participants were randomly assigned to receive either D-serine (n=20) or placebo (n=24); 35 had assessable data (15 D-serine, 20 placebo). D-serine induced a 35.7% (SD 17.8) improvement in negative symptoms, which was significant compared with placebo (mean final SOPS negative score 7.6 [SEM 1.4] for D-serine group vs 11.3 [1.2] for placebo group; d=0.68, p=0.03). Five participants who received D serine and nine participants who received placebo discontinued the study early because of withdrawn consent or loss to follow-up (n=8), conversion to psychosis (n=2), laboratory-confirmed adverse events (n=2), or protocol deviations (n=2). INTERPRETATION: This study supports use of NMDAR-based interventions, such as D serine, for treatment of prodromal symptoms of schizophrenia. On the basis of observed effect sizes, future studies with sample sizes of about 40 per treatment group would be needed for confirmation of beneficial effects on symptoms and NMDAR-related inflammatory changes. Long-term studies are needed to assess effects on psychosis conversion in individuals at clinical high risk of schizophrenia. FUNDING: National Institutes of Health. PMID- 26360285 TI - Pharmacological prevention of post-traumatic stress disorder and acute stress disorder: a systematic review and meta-analysis. AB - BACKGROUND: An increasing number of studies have investigated the pharmacological prevention of post-traumatic stress disorder (PTSD) and acute stress disorder (ASD). This is the first systematic review to examine the effects of pharmacotherapies (eg, beta blockers, hydrocortisone, and selective serotonin re uptake inhibitors) given within the first month after a traumatic or aversive event to prevent PTSD or ASD compared with no pharmacotherapy or placebo control. METHODS: A systematic literature search in PubMed, PsycINFO, Embase, and the Cochrane database of randomised trials was done. Studies included randomised controlled trials, controlled clinical trials, and cohort studies; their overall quality was low to moderate. We computed the pooled incidence risk ratio (IRR): the risk of incidence of PTSD or ASD in the pharmacotherapy groups relative to the incidence of PTSD or ASD in the control groups. Additionally, we computed Hedges'g effect sizes for PTSD or ASD continuous outcomes. FINDINGS: 15 studies met inclusion criteria (1765 individuals). Pharmacotherapy was more effective in preventing PTSD or ASD than placebo or no intervention (14 studies, 1705 individuals, IRR 0.65, 95% CI 0.55-0.78; number needed to treat 11.36), although no effect was found when only randomised controlled trials were included (ten studies, 300 individuals, IRR 0.69, 95% CI 0.40-1.21). Hydrocortisone showed a large effect in reducing the risk of PTSD (five studies, 164 individuals, IRR 0.38, 95% CI 0.16-0.92). INTERPRETATION: No firm evidence was found for the efficacy of all early pharmacotherapies in the prevention of PTSD or ASD, but hydrocortisone reduced the risk of developing PTSD. The small number of studies and their limited methodological quality cast uncertainty about the effects. FUNDING: None. PMID- 26360287 TI - The epidemiology of diabetes in psychotic disorders. AB - Diabetes is highly prevalent in people with psychotic disorders, including schizophrenia and schizoaffective disorders. Exact prevalence is difficult to estimate, since diabetes is often underdiagnosed in people with psychosis. Results of several studies show that the prevalence of diabetes exceeds that in the general population, with documented prevalence in those with psychosis ranging from 1.26% to 50% across studies (median 13%). The association between diabetes and psychosis is complex and multifactorial. Many of the traditional risk factors for disease have increased prevalence in patients with psychotic disorders. In addition to these traditional risk factors, people with psychosis have unique risks that might have additive or even synergistic effects. These risks include the use of antipsychotic medication, the effects of adverse social determinants of health, and genetic loading. Despite evidence that rates of diabetes are increased in individuals with psychosis, many of these patients are not diagnosed or treated, resulting in increased diabetes-associated morbidity and mortality. Specific patient factors, provider issues, and systems-level factors contribute to the treatment gap. Interventions at both the clinical and public health levels are needed to successfully address this problem. PMID- 26360286 TI - Substance use disorders, psychiatric disorders, and mortality after release from prison: a nationwide longitudinal cohort study. AB - BACKGROUND: High mortality rates have been reported in people released from prison compared with the general population. However, few studies have investigated potential risk factors associated with these high rates, especially psychiatric determinants. We aimed to investigate the association between psychiatric disorders and mortality in people released from prison in Sweden. METHODS: We studied all people who were imprisoned since Jan 1, 2000, and released before Dec 31, 2009, in Sweden for risks of all-cause and external-cause (accidents, suicide, homicide) mortality after prison release. We obtained data for substance use disorders and other psychiatric disorders, and criminological and sociodemographic factors from population-based registers. We calculated hazard ratios (HRs) by Cox regression, and then used them to calculate population attributable fractions for post-release mortality. To control for potential familial confounding, we compared individuals in the study with siblings who were also released from prison, but without psychiatric disorders. We tested whether any independent risk factors improved the prediction of mortality beyond age, sex, and criminal history. FINDINGS: We identified 47,326 individuals who were imprisoned. During a median follow-up time of 5.1 years (IQR 2.6-7.5), we recorded 2874 (6%) deaths after release from prison. The overall all-cause mortality rate was 1205 deaths per 100,000 person-years. Substance use disorders significantly increased the rate of all-cause mortality (alcohol use: adjusted HR 1.62, 95% CI 1.48-1.77; drug use: 1.67, 1.53-1.83), and the association was independent of sociodemographic, criminological, and familial factors. We identified no strong evidence that other psychiatric disorders increased mortality after we controlled for potential confounders. In people released from prison, 925 (34%) of all-cause deaths in men and 85 (50%) in women were potentially attributable to substance use disorders. Substance use disorders were also an independent determinant of external-cause mortality, with population attributable fraction estimates at 42% in men and 70% in women. Substance use disorders significantly improved the prediction of external-cause mortality, in addition to sociodemographic and criminological factors. INTERPRETATION: Interventions to address substance use disorders could substantially decrease the burden of excess mortality in people released from prison, but might need to be provided beyond the immediate period after release. FUNDING: Wellcome Trust, Swedish Research Council, and the Swedish Research Council for Health, Working Life and Welfare. PMID- 26360288 TI - Pathophysiological mechanisms of increased cardiometabolic risk in people with schizophrenia and other severe mental illnesses. AB - Patients with schizophrenia have increased mortality and morbidity compared with the general population. These patients have a 20-year shorter lifespan than peers without schizophrenia, mainly due to premature cardiovascular disease, suicide, and cancer. Patients with severe mental illness are at increased risk for cardiovascular disease related to increased incidence of diabetes, hypertension, smoking, poor diet, obesity, dyslipidaemia, metabolic syndrome, low physical activity, and side-effects of antipsychotic drugs. Some second-generation antipsychotics (eg, clozapine, olanzapine, quetiapine, and risperidone) are associated with an increased risk of weight gain and obesity, impaired glucose tolerance and new-onset diabetes, hyperlipidaemia, and cardiovascular disease. The mechanisms by which schizophrenia and patients with severe mental illness are susceptible to cardiometabolic disorders are complex and include lifestyle risks and direct and indirect effects of antipsychotic drugs. An understanding of these risks might lead to effective interventions for prevention and treatment of cardiometabolic disorders in schizophrenia and severe mental illness. PMID- 26360289 TI - Clinical management of comorbid diabetes and psychotic disorders. AB - Individuals with psychotic disorders experience substantial health disparities with respect to diabetes, including increased risk of incident diabetes and of poor diabetes outcomes (eg, diabetes complications and mortality). Low-quality medical care for diabetes is a significant contributor to these poor health outcomes. A thoughtful approach to both diabetes pharmacotherapy and drug management for psychotic disorders is essential, irrespective of whether treatment is given by a psychiatrist, a primary care provider, or an endocrinologist. Exposure to drugs with high metabolic liability should be minimised, and both psychiatric providers and medical providers need to monitor patients to ensure that medical care for diabetes is adequate. Promising models of care management and team approaches to coordination and integration of care highlight the crucial need for communication and cooperation among medical and psychiatric providers to improve outcomes in these patients. Evidence-based programmes that promote weight loss or smoking cessation need to be more accessible for these patients, and should be available in all the settings where they access care. PMID- 26360290 TI - Transgender, through a modern looking glass. PMID- 26360291 TI - Perspectives of Patients, Doctors and Medical Students at a Public University Hospital in Rio de Janeiro Regarding Tuberculosis and Therapeutic Adherence. AB - INTRODUCTION: The World Health Organization (WHO) identifies 8.7 million new cases of tuberculosis (TB) annually around the world. The unfavorable outcomes of TB treatment prevent the achievement of the WHO's cure target. GOAL: To evaluate existing intersections in the conceptions relative to the knowledge of TB, the experience of the illness and the treatment. METHODS: Doctors, medical students and patients were selected from a public university in Rio de Janeiro, Brazil, from 2011 to 2013. The data were obtained by semi-structured individual and focus group interviews, participant observation and a field journal. The inclusion of patients was interrupted due to saturation, and the inclusion of doctors and medical students stopped due to exhaustion. The theoretical background included symbolic Interactionism, and the analysis used rounded Theory. The analysis prioritized the actions/interactions axis. RESULTS: Twenty-three patients with pulmonary TB, seven doctors and 15 medical students were included. In the interviews, themes such as stigma, self-segregation, and difficulties in assistance emerged, in addition to defense mechanisms such as denial, rationalization, isolation and other mental mechanisms, including guilt, accountability and concealment of the disease. Aspects related to the assistance strategy, the social support network, bonding with the healthcare staff and the doctor-patient relationship were highlighted as adherence enablers. Doctors and students recommended an expansion of the theoretical and practical instruction on TB during medical students' education. The existence of health programs and policies was mentioned as a potential enabler of adherence. CONCLUSION: The main concepts identified were the stigma, self-segregation, guilt, responsibility, concealment and emotional repercussions. In relation to the facilitation of therapeutic adherence, the concepts identified were the bonds with healthcare staff, the doctor-patient relationship, assistance and educational health strategies. PMID- 26360292 TI - Autophagy Protects from Trastuzumab-Induced Cytotoxicity in HER2 Overexpressing Breast Tumor Spheroids. AB - Multicellular tumor spheroids represent a 3D in vitro model that mimics solid tumor essential properties including assembly and development of extracellular matrix and nutrient, oxygen and proliferation gradients. In the present study, we analyze the impact of 3D spatial organization of HER2-overexpressing breast cancer cells on the response to Trastuzumab. We cultured human mammary adenocarcinoma cell lines as spheroids with the hanging drop method and we observed a gradient of proliferating, quiescent, hypoxic, apoptotic and autophagic cells towards the inner core. This 3D organization decreased Trastuzumab sensitivity of HER2 over-expressing cells compared to monolayer cell cultures. We did not observe apoptosis induced by Trastuzumab but found cell arrest in G0/G1 phase. Moreover, the treatment downregulated the basal apoptosis only found in tumor spheroids, by eliciting protective autophagy. We were able to increase sensitivity to Trastuzumab by autophagy inhibition, thus exposing the interaction between apoptosis and autophagy. We confirmed this result by developing a resistant cell line that was more sensitive to autophagy inhibition than the parental BT474 cells. In summary, the development of Trastuzumab resistance relies on the balance between death and survival mechanisms, characteristic of 3D cell organization. We propose the use of spheroids to further improve the understanding of Trastuzumab antitumor activity and overcome resistance. PMID- 26360293 TI - Repeated-High-Intensity-Running Activity and Internal Training Load of Elite Rugby Sevens Players During International Matches: A Comparison Between Halves. AB - PURPOSE: To describe the repeated-high-intensity activity and internal training load of rugby sevens players during international matches and to compare the differences between the 1st and 2nd halves. METHODS: Twelve international-level male rugby sevens players were monitored during international competitive matches (n = 30 match files) using global positioning system technology and heart-rate monitoring. RESULTS: The relative total distance covered by the players throughout the match was 112.1 +/- 8.4 m/ min. As a percentage of total distance, 35.0% (39.2 +/- 9.0 m/min) was covered at medium speed and 17.1% (19.2 +/- 6.8 m/min) at high speed. A substantial decrease in the distance covered at >14.0 km/h and >18.0 km/h, the number of accelerations of >2.78 m/s and >4.0 m/s, repeated-sprint sequences interspersed with <=60 s rest, and repeated acceleration sequences interspersed with <=30 s or <=60 s rest was observed in the 2nd half compared with the 1st half. A substantial increase in the mean heart rate (HR), HRmax, percentage of time at >80% HRmax and at >90% HRmax, and Edwards training load was observed in the 2nd half compared with the 1st half. CONCLUSION: This study provides evidence of a pronounced reduction in high intensity and repeated-high-intensity activities and increases in internal training load in rugby sevens players during the 2nd half of international matches. PMID- 26360294 TI - Herbivore-Alga Interaction Strength Influences Spatial Heterogeneity in a Kelp Dominated Intertidal Community. AB - There is a general consensus that marine herbivores can affect algal species composition and abundance, but little empirical work exists on the role of herbivores as modifiers of the spatial structure of resource assemblages. Here, we test the consumption/bulldozing effects of the molluscan grazer Enoplochiton niger and its influence on the spatial structure of a low intertidal community dominated by the bull kelp Durvillaea antarctica and the kelp Lessonia spicata. Through field experiments conducted at a rocky intertidal shore in north-central Chile (~30 degrees -32 degrees S), the edge of the grazer and algae geographic distributions, we estimated the strength and variability of consumptive effects of the grazer on different functional group of algae. We also used data from abundance field surveys to evaluate spatial co-occurrence patterns of the study species. Exclusion-enclosure experiments showed that E. niger maintained primary space available by preventing algal colonization, even of large brown algae species. The grazing activity of E. niger also reduced spatial heterogeneity of the ephemeral algal species, increasing bare space availability and variability through time in similar ways to those observed for the collective effect with other grazers. Overall, our result suggests that E. niger can be considered an important modifier of the spatial structure of the large brown algae-dominated community. Effects of E. niger on resource variability seem to be directly related to its foraging patterns, large body size, and population densities, which are all relevant factors for management and conservation of the large brown algae community. Our study thus highlights the importance of considering functional roles and identity of generalist consumers on spatial structure of the entire landscape. PMID- 26360295 TI - DMT1 iron uptake in the PNS: bridging the gap between injury and regeneration. AB - Previous studies by our group demonstrated the key role of iron in Schwann cell maturation through an increase in cAMP, PKA activation and CREB phosphorylation. These studies opened the door to further research on non-transferrin-bound iron uptake, which revealed the presence of DMT1 mRNA all along SC progeny, hinting at a constitutive role of DMT1 in ensuring the provision of iron in the PNS. In light of these previous results, the present work evaluates the participation of DMT1 in the remyelination process following a demyelinating lesion promoted by sciatic nerve crush--a reversible model of Wallerian degeneration. DMT1 was observed to colocalize with a SC marker S100beta at all survival times analyzed. In turn, the assessment of DMT1 mRNA expression exhibited an increase 7 days post injury, while DMT1 protein levels showed an increase 14 days after crush at the lesion site and distal stump; finally, an increase in iron levels became evident as from 14 days post-injury, in parallel with DMT1 values. To sum up, the present work unveils the role of DMT1 in mediating the neuroregenerative action of iron. PMID- 26360296 TI - Amorphous V2O5-P2O5 as high-voltage cathodes for magnesium batteries. AB - A deep investigation of amorphous V2O5-P2O5 powders for magnesium batteries communicates the vital properties to achieving the superior electrochemical performance at a 75 : 25 V2O5 : P2O5 molar ratio. The manipulation of the inter layer spacing and amorphization of V2O5 can enhance Mg(2+) diffusion and afford a cathode with high-voltage reversibility. PMID- 26360297 TI - Detection of Langat virus by TaqMan real-time one-step qRT-PCR method. AB - Langat virus (LGTV), one of the members of the tick-borne encephalitis virus (TBEV) complex, was firstly isolated from Ixodes granulatus ticks in Malaysia. However, the prevalence of LGTV in ticks in the region remains unknown. Surveillance for LGTV is therefore important and thus a tool for specific detection of LGTV is needed. In the present study, we developed a real-time quantitative reverse-transcription-polymerase chain reaction (qRT-PCR) for rapid detection of LGTV. Our findings showed that the developed qRT-PCR could detect LGTV at a titre as low as 0.1 FFU/ml. The detection limit of the qRT-PCR assay at 95% probability was 0.28 FFU/ml as determined by probit analysis (p <= 0.05). Besides, the designed primers and probe did not amplify ORF of the E genes for some closely related and more pathogenic viruses including TBEV, Louping ill virus, Omsk hemorrhagic fever virus (OHFV), Alkhurma virus (ALKV), Kyasanur Forest Disease virus (KFDV) and Powassan virus (POWV) which showed the acceptable specificity of the developed assay. The sensitivity of the developed method also has been confirmed by determining the LGTV in infected tick cell line as well as LGTV- spiked tick tissues. PMID- 26360298 TI - An Alternative Reaction Course in O-Glycosidation with O-Glycosyl Trichloroacetimidates as Glycosyl Donors and Lewis Acidic Metal Salts as Catalyst: Acid-Base Catalysis with Gold Chloride-Glycosyl Acceptor Adducts. AB - Gold(III) chloride as catalyst for O-glycosyl trichloroacetimidate activation revealed low affinity to the glycosyl donor but high affinity to the hydroxy group of the acceptor alcohol moiety, thus leading to catalyst-acceptor adduct formation. Charge separation in this adduct, increasing the proton acidity and the oxygen nucleophilicity, permits donor activation and concomitant acceptor transfer in a hydrogen-bond mediated S(N)2-type transition state. Hence, the sequential binding between acceptor and catalyst and then with the glycosyl donor enables self-organization of an ordered transition-state. This way, with various acceptors, even at temperatures below -60 degrees C, fast and high yielding glycosidations in high anomeric selectivities were recorded, showing the power of this gold(III) chloride acid-base catalysis. Alternative reaction courses via hydrogen chloride or HAuCl4 activation or intermediate generation of glycosyl chloride as the real donor could be excluded. With partially O-protected acceptors, prone to bidentate ligation to gold(III) chloride, particularly high reactivities and anomeric selectivities were observed. Gold(I) chloride follows the same catalyst-acceptor adduct driven acid-base catalysis reaction course. PMID- 26360299 TI - In Vivo Curdlan/Cellulose Bionanocomposite Synthesis by Genetically Modified Gluconacetobacter xylinus. AB - Bacterial cellulose pellicle produced by Gluconacetobacter xylinus (G. xylinus) is one of the best biobased materials having a unique supernetwork structure with remarkable physiochemical properties for a wide range of medical and tissue engineering applications. It is still necessary to modify them to obtain materials suitable for biomedical use with satisfactory mechanical strength, biodegradability, and bioactivity. The aim of this research was to develop a gene transformation route for the production of bacterial cellulose/Curdlan (beta-1,3 glucan) nanocomposites by separate but simultaneous in vivo synthesis of cellulose and Curdlan. Modification of the cellulose-nanofiber-producing system of G. xylinus enabled Curdlan to be synthesized simultaneously with cellulose nanofibers in vivo, resulting in biopreparation of nanocomposites. The obtained Curdlan/cellulose composites were characterized, and their properties were compared with those of normal bacterial cellulose pellicles, indicating that Curdlan mixed with the cellulose nanofibers at the nanoscale without disruption of the nanofiber network structure in the pellicle. PMID- 26360301 TI - G-Quadruplex DNA- and RNA-Specific-Binding Proteins Engineered from the RGG Domain of TLS/FUS. AB - Human telomere DNA (Htelo) and telomeric repeat-containing RNA (TERRA) are integral telomere components containing the short DNA repeats d(TTAGGG) and RNA repeats r(UUAGGG), respectively. Htelo and TERRA form G-quadruplexes, but the biological significance of their G-quadruplex formation in telomeres is unknown. Compounds that selectively bind G-quadruplex DNA and RNA are useful for understanding the functions of each G-quadruplex. Here we report that engineered Arg-Gly-Gly repeat (RGG) domains of translocated in liposarcoma containing only Phe (RGGF) and Tyr (RGGY) specifically bind and stabilize the G-quadruplexes of Htelo and TERRA, respectively. Moreover, RGGF inhibits trimethylation of both histone H4 at lysine 20 and histone H3 at lysine 9 at telomeres, while RGGY inhibits only H3 trimethylation in living cells. These findings indicate that G quadruplexes of Htelo and TERRA have distinct functions in telomere histone methylation. PMID- 26360300 TI - Steering Evolution with Sequential Therapy to Prevent the Emergence of Bacterial Antibiotic Resistance. AB - The increasing rate of antibiotic resistance and slowing discovery of novel antibiotic treatments presents a growing threat to public health. Here, we consider a simple model of evolution in asexually reproducing populations which considers adaptation as a biased random walk on a fitness landscape. This model associates the global properties of the fitness landscape with the algebraic properties of a Markov chain transition matrix and allows us to derive general results on the non-commutativity and irreversibility of natural selection as well as antibiotic cycling strategies. Using this formalism, we analyze 15 empirical fitness landscapes of E. coli under selection by different beta-lactam antibiotics and demonstrate that the emergence of resistance to a given antibiotic can be either hindered or promoted by different sequences of drug application. Specifically, we demonstrate that the majority, approximately 70%, of sequential drug treatments with 2-4 drugs promote resistance to the final antibiotic. Further, we derive optimal drug application sequences with which we can probabilistically 'steer' the population through genotype space to avoid the emergence of resistance. This suggests a new strategy in the war against antibiotic-resistant organisms: drug sequencing to shepherd evolution through genotype space to states from which resistance cannot emerge and by which to maximize the chance of successful therapy. PMID- 26360302 TI - Using co-metabolism to accelerate synthetic starch wastewater degradation and nutrient recovery in photosynthetic bacterial wastewater treatment technology. AB - Starch wastewater is a type of nutrient-rich wastewater that contains numerous macromolecular polysaccharides. Using photosynthetic bacteria (PSB) to treat starch wastewater can reduce pollutants and enhance useful biomass production. However, PSB cannot directly degrade macromolecular polysaccharides, which weakens the starch degradation effect. Therefore, co-metabolism with primary substances was employed in PSB wastewater treatment to promote starch degradation. The results indicated that co-metabolism is a highly effective method in synthetic starch degradation by PSB. When malic acid was used as the optimal primary substrate, the chemical oxygen demand, total sugar, macromolecules removal and biomass yield were considerably higher than when primary substances were not used, respectively. Malic acid was the primary substrate that played a highly important role in starch degradation. It promoted the alpha-amylase activity to 46.8 U and the PSB activity, which induced the degradation of macromolecules. The products in the wastewater were ethanol, acetic acid and propionic acid. Ethanol was the primary product throughout the degradation process. The introduction of co-metabolism with malic acid to treat wastewater can accelerate macromolecules degradation and bioresource production and weaken the acidification effect. This method provides another pathway for bioresource recovery from wastewater. This approach is a sustainable and environmentally friendly wastewater treatment technology. PMID- 26360303 TI - Optimization, in vitro cytotoxicity and penetration capability of deformable nanovesicles of paclitaxel for dermal chemotherapy in Kaposi sarcoma. AB - Although much research has been published on ways to overcome the low oral bioavailability of paclitaxel, exploration of novel drug delivery systems that can target paclitaxel deep in to the dermal areas in AIDS-related Kaposi sarcoma (KS) have not yet been reported. Our aim was to develop deformable nanovesicles of paclitaxel capable of being used in dermal chemotherapy, especially deep into the dermal areas of AIDS related KS. Deformable nanovesicular formulations (TS1 TS15) composed of soya lecithin and span80 were prepared by the rotary evaporation sonication method within the constraints of our Box-Behnken design. The formulations were subjected to vesicle characterization and ex vivo permeation. The optimized vesicular suspension was formulated as a gel and assessed for in vitro cytotoxicity and penetration characteristics by confocal laser scanning microscopy (CLSM). TS9 with vesicle size characteristics of 185.76 +/- 2.15 nm, zeta potential of -23.2 mV, deformability index = 138.02 and cumulative drug permeation of 89.80 +/- 1.84% was identified as the optimized formulation. TEM revealed spherical vesicles with firm boundaries that were stable at 4 degrees C. TS9 was developed as carbopol 934P gel (TG) and compared with the control gel (CG) made with the pure drug (paclitaxel). TG showed significantly higher (p < 0.05) in vitro drug permeation and flux compared to the CG. In vitro cytotoxicity study on KSY-1 cell lines revealed higher IC50 (<=17) for TS against IC50 <=19 for TG. CLSM confirmed the penetrating potential of transfersomes via TG to the dermal layers of skin, the proposed target site. Conclusively, deformable nonovesicles of paclitaxel appear as a feasible alternative to the conventional formulations of paclitaxel in the management of AIDS-related KS. PMID- 26360304 TI - Evaluation of lymphoid tissue structure in Sole (Euryglossa orientalis) and Yellowfin Seabream (Acanthopagus latus) affected by environmental contaminants in the Persian Gulf. AB - This study sought to analyze structures of lymphatic tissues in two commercial fish species, e.g. Sole (Euryglossa orientalis) and Yellowfin Seabream (Acanthopagus latus), collected from five stations with varying levels of pollution in the Musa Creek near the Persian Gulf, e.g. Petro-chemical, Gaafari, Majidieh, Ghazaleh and Zangi Stations. Samples from Genaveh Station located outside Musa Creek were collected as controls. To correlate findings of changes in the studied tissues with local pollution status, levels of Hg, Pb, Zn, Cu and Cd were measured in sediments and water at each station. Fish were caught from the sampling stations; the spleen and head kidney were collected and sections prepared to permit histologic evaluation. The results indicated that, in both species, the most common changes were observed in fish collected near the Petrochemical station and included an increase in melano-macrophage aggregates, hemorrhage and damaged/dead red blood cells in the spleen; in the head kidney, the major findings were melano-macrophage aggregation, hemorrhage and lifting of the tubular basement membrane. No pathological alternations were noted in the spleen and head kidney of fish from the Zangi station. Samples of A. latus collected from Gaafari station and of E. orientalis from Majidieh station also had pathological changes. No significant differences were found in the tissue structures of fish recovered from the Zangi and Genaveh control stations. The concentrations for nearly all of the studied metals in sediment and water samples collected from the different stations followed the pattern: Petrochemical station ~ Majidieh ~ Gaafari >> Ghazaleh > Zangi Stations. From the data, it was concluded that changes in lymphoid tissues of the fish studied here "correlated" with geographical conditions and sources of pollution at the different test stations. What these changes mean to the long-term health of both species remains to be determined in ongoing studies. PMID- 26360305 TI - Technology and Sleep: How Electronic Media Exposure Has Impacted Core Concepts of Sleep Medicine. PMID- 26360306 TI - Reply to comment on "influence of microwaves on the water surface tension". PMID- 26360307 TI - A program of telementoring in laparoscopic bariatric surgery. AB - BACKGROUND: This study proposes a system for teaching and surgical support with the benefits of online Information and Communications Technology (ITC) -based telementoring for laparoscopic bariatric surgery (LBS). MATERIAL AND METHODS: A system of telementoring was established between a university center and two community hospitals. Telementoring was performed via internet protocol using a direct point-to-point connection, ASDL 1.2 Mbps, time delay 150 ms, 256-bit advanced encryption standard (AES). In the period of time selected, all interventions for LBS in both hospitals were included. When patients agree with telementoring, data outcomes (operating time, hospital stay, conversion to open surgery and complications) were collected. The rest of these interventions were recorded. RESULTS: Thirty-six patients underwent elective LBS, 20 of whom were referred and accepted for telementoring. Patients selected without telementoring took longer: 200 (46) min vs 139 (33) min, p < 0.01. There were two conversions in non-mentored groups. The hospital stay was 4.6 (0.5) days for telementored interventions and 6.7 (0.5) days without mentoring (p < 0.01). Four patients (12,5%) in non-mentored groups suffered minor complications. CONCLUSIONS: This program supports the safety and feasibility of telementoring in LBS. Telementoring is an alternative in community hospitals because it can improve the quality of advanced procedures of laparoscopic surgery. PMID- 26360308 TI - Pressure algometry measurement of canine muscular pain near the thoracolumbar junction: evaluation of a modified technique. AB - OBJECTIVE: To evaluate the utility of pressure algometry for measuring muscular pain in dogs by using a modified technique intended to prevent the development of a learned apprehension response. STUDY DESIGN: Prospective randomized clinical trial. ANIMALS: Sixty-three client-owned dogs with a history of restricted comfort or mobility. METHOD: Pressure algometry was used to measure the mechanical nociceptive threshold (MNT) in eight locations around the thoracolumbar junction. Dogs were assigned to one of two groups: group A dogs (n = 22) were placed on a restricted exercise program, while group B dogs (n = 25) were placed on a restricted exercise program and were administered combined acupuncture and manual therapy treatment (CAMT). After data collection in groups A and B was complete, animals were recruited for a third (control) group, C (n = 16), that had no exercise restriction or treatment. Algometry measurements were performed on four occasions over 28 days using a technique intended to prevent the dogs from developing a learned apprehension response. Measurements from eight locations were pooled and analyzed for changes over time. RESULTS: Increases in MNTs over time at all locations tested were identified in groups A and B. In group C there were no significant changes in MNT or evidence of a learned apprehension response. CONCLUSION AND CLINICAL RELEVANCE: MNTs in dogs without exercise restriction or CAMT were consistently repeatable and unchanged over time, indicating that there was no learned apprehension response to pressure algometry using the modified technique. Therefore, the increasing MNT values with time in dogs administered exercise restriction with or without CAMT suggests improved muscular comfort of the thoracolumbar region. Although further research is needed, use of this modified technique should improve the utility of pressure algometry for measuring muscular pain in dogs. PMID- 26360309 TI - Trauma-related pathological dissociation in a case with cerebral palsy. AB - This article provides a case report of a Chinese-Cantonese female with both cerebral palsy and dissociative identity disorder. To my knowledge, this is the first report of a case with dissociative identity disorder from Hong Kong, as well as the first report of a case with both dissociative identity disorder and cerebral palsy in the literature. Large-sample studies should be undertaken in the future to investigate the prevalence of dissociative disorders in a variety of populations in Hong Kong, including individuals with diagnosed brain diseases. PMID- 26360315 TI - Validation of an audio computer-assisted self-interview (ACASI) version of the alcohol, smoking and substance involvement screening test (ASSIST) in primary care patients. AB - BACKGROUND AND AIMS: To address barriers to implementing the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) in medical settings, we adapted the traditional interviewer-administered (IA) ASSIST to an audio-guided computer assisted self-interview (ACASI) format. This study sought to validate the ACASI ASSIST by estimating the concordance, correlation and agreement of scores generated using the ACASI versus the reference standard IA ASSIST. Secondary aims were to assess feasibility and compare ASSIST self-report to drug testing results. DESIGN: Participants completed the ACASI and IA ASSIST in a randomly assigned order, followed by drug testing. SETTING: Urban safety-net primary care clinic in New York City, USA. PARTICIPANTS: A total of 393 adult patients. MEASUREMENTS: Scores generated by the ACASI and IA ASSIST; drug testing results from saliva and hair samples. FINDINGS: Concordance between the ACASI and IA ASSIST in identifying moderate-high-risk use was 92-99% for each substance class. Correlation was excellent for global scores [intraclass correlation (ICC) = 0.937, confidence interval (CI) = 0.924-0.948] and for substance-specific scores for tobacco (ICC = 0.927, CI = 0.912-0.940), alcohol (ICC = 0.912, CI = 0.893 0.927) and illicit drugs (ICC = 0.854, CI = 0.854-0.900) and good for prescription drugs (ICC = 0.676, CI = 0.613-0.729). Ninety-four per cent of differences in global scores fell within anticipated limits of agreement. Among participants with a positive saliva test, 74% self-reported use on the ACASI ASSIST. The ACASI ASSIST required a median time of 3.7 minutes (range 0.7-15.4), and 21 (5.3%) participants requested assistance. CONCLUSIONS: The computer self administered Alcohol, Smoking and Substance Involvement Screening Test appears to be a valid alternative to the interviewer-administered approach for identifying substance use in primary care patients. PMID- 26360316 TI - The impact of surgical trainee participation on sinus surgery outcomes. AB - OBJECTIVES/HYPOTHESIS: To determine the effect of otolaryngology trainee participation on clinical outcomes in patients who undergo endoscopic sinus surgery (ESS) for chronic rhinosinusitis. STUDY DESIGN: Secondary analysis of prospectively collected data. METHODS: Patients enrolled in a sinus surgery outcomes study between May 2011 and March 2013 were stratified into two groups- those who were operated on by an attending alone and those operated on by an attending with a trainee present (resident, fellow, or both). Patients completed quality of life (QOL) surveys including the Chronic Sinusitis Survey (CSS), 22 item Sino-Nasal Outcome Test (SNOT-22), and EuroQol 5-dimension survey preoperatively and 1 year postoperatively. Operative time, estimated blood loss (EBL), complication rates, and survey scores were compared between groups. RESULTS: The study population consisted of 452 patients. The attending alone (n = 119) and trainee (n = 333) groups were statistically comparable in terms of patient demographics, disease severity, and extent of surgery. Mean operative time was significantly shorter in the attending-alone group (80.0 vs. 90.6 minutes, P < .01). Mean EBL (105 mL attending vs. 117 mL trainee, P = .39) and complication rates (3.3% attending vs. 0.6% trainee, P = .07) were similar between groups. Observed changes in QOL measures following ESS were comparable between groups, although absolute improvement in the SNOT-22 scores (19.0 attending vs. 24.5 trainee, P = .05) did show a trend toward greater improvement in the trainee group. CONCLUSIONS: Trainee participation in ESS is associated with prolongation in surgical time; however, such participation was not found to adversely affect patient safety or clinical outcomes. LEVEL OF EVIDENCE: 2b. PMID- 26360317 TI - Correction to Synthesis of Fluorenes via Tandem Copper-Catalyzed [3 + 2] Cycloaddition and Rhodium-Catalyzed Denitrogenative Cyclization in a 5-Exo Mode from 2-Ethynylbiaryls and N-Sulfonyl Azides in One-Pot. PMID- 26360318 TI - Wheat allergy in celiac children. PMID- 26360319 TI - Palladium-Catalyzed Triple Cyclization of 2,7-Alkadiynylic Carbonates with Allenes Bearing a Carbon Nucleophile. AB - Palladium-catalyzed tandem reactions of 2,7-alkadiynylic carbonates with allenes bearing a carbon nucleophile such as malonate and bis(phenylsulfonyl)methane for the efficient syntheses of fused tricycles, such as 3,5,6,7-tetrahydro-1H indeno[5,6-c]furan, 1,2,3,5,6,7-hexahydrocyclopenta[f]isoindole, and 1,2,3,5,6,7 hexahydro-s-indacene derivatives, have been reported. The reaction forms two five membered rings and one benzene ring fusing them in the middle. PMID- 26360320 TI - Reply. PMID- 26360321 TI - Detection of Segmental Renal Ischemia by Diffusion-Weighted Magnetic Resonance Imaging: Clinical Utility for Diagnosis of Renovascular Hypertension. PMID- 26360322 TI - Cytochrome P450-mediated metabolism of the synthetic cannabinoids UR-144 and XLR 11. AB - In recent years, synthetic cannabinoids have emerged in the illicit drug market, in particular via the Internet, leading to abuse of these drugs. There is currently limited knowledge about the specific enzymes involved in the metabolism of these drugs. In this study, we investigated the cytochrome P450 (CYP) enzymes involved in the metabolism of the two synthetic cannabinoids (1-pentyl-1H-indol-3 yl)-(2,2,3,3-tetramethylcyclopropyl)methanone (UR-144) and [1-(5-fluoropentyl)-1H indol-3-yl)](2,2,3,3-tetramethylcyclopropyl)methanone (XLR-11). This study extends previous studies by identifying the specific CYP enzymes involved in the metabolism of UR-144 and XLR-11 utilizing a panel of nine recombinant enzymes (CYP1A2, 2B6, 2C8, 2C9, 2C18, 2C19, 2D6, 3A4, and 2E1). This is followed by an investigation of the effect of specific inhibitors targeted against CYP1A2, 2B6, 2C9, 2C19, 2D6 and 3A4 in human liver microsomes (HLM). Incubations of UR-144 and XLR-11 with recombinant CYP enzymes revealed that UR-144 and XLR-11 are extensively metabolized by CYP3A4 at the tetramethylcyclopropyl (TMCP) moiety, but also CYP1A2 and CYP2C19 showed activity. Inhibition of CYP3A4 in HLM attenuated the metabolism of UR-144 and XLR-11, while inhibition of the other CYP enzymes in HLM had only minor effects. Thus, CYP3A4 is the major contributor to the CYP mediated metabolism of UR-144 and XLR-11 with minor contributions from CYP1A2. Users of UR-144 and XLR-11 are thus subject to the influence of potential drug-drug interactions, if they are concomitantly medicated with CYP3A4 inducers (e.g. some antiepileptics) or inhibitors (e.g. some antifungal drugs). Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26360323 TI - Gold and Silver Chains Supported by Linear Hexaphosphine Ligands. AB - A new linear hexaphosphine, rac-cis,cis,trans bis{[(diphenylphosphinomethyl)phenylphosphinomethyl]phenylphosphino}methane (P6), was synthesized and isolated as a pure isomer, confirmed by transforming to the corresponding phosphine sulfide. The methylene-bridged linear hexaphosphine readily organized flexible gold(I) and silver(I) hexanuclear chains, [M6(MU P6)2]X6 (X6 = (OTf)6, M = Au (1), Ag (2); X6 = Cl2(PF6)4, M = Au (3)). The hexaphosphine also supported a tetrasilver(I) complex [Ag4(MU-P6)2](OTf)4 (4), which was readily transformed by treatment with AgOTf into 3, revealing a drastic alternation of the two P6 arrangement. The hexagold(I) chains exhibited a considerably red-shifted absorption (~410 nm) and emission (540-580 nm) to (1) [5dsigma*->6psigma] and from (3) [5dsigma*->6psigma] excited states of the metal centers, respectively. The new linear hexaphosphine could be a useful tool to construct linear metal clusters as subnano building blocks. PMID- 26360324 TI - Carotid Intima-Media Thickness is Inversely Related to Bone Density in Female but not in Male Patients with Acute Stroke. AB - BACKGROUND AND PURPOSE: Atherosclerosis and osteoporosis are two major public health problems. It is still uncertain whether an abnormal carotid ultrasonography, either increased intima-media thickness (IMT) or plaque thickness, is associated with osteoporosis in acute ischemic stroke patients. To investigate the possible relationships between osteoporosis and carotid atherosclerosis, we evaluated the correlation between carotid IMT/plaque thickness and bone mineral density (BMD) in acute ischemic stroke patients. METHODS: Patients having their first ischemic stroke within seven days were screened for the study. The IMT was scanned approximately 10 mm proximal to the beginning of the dilatation of the carotid bulb. The plaques were measured in both common and internal carotid arteries. The BMD was measured at total hip and lumbar spine in the anterior-posterior projection, using dual-energy x-ray absorptiometry. RESULTS: A total of 155 patients were enrolled in the study and the mean age was 68.3 +/- 10.34 years. Multiple linear regression analysis reveals that age (P < .001), smoking (P = .016), and osteoporosis (P = .001) were significantly associated with increased carotid IMT/plaque thickness. Old age, current smoking, and osteoporosis were significantly related to increased IMT/plaque thickness in acute ischemic stroke patients. In women, IMT/plaque thickness was significantly related to age (P = .01) and osteoporosis (P = .025). In men, though there was no significant relationship, a trend toward old age and having osteoporosis was observed in increased IMT/plaque thickness (P = .051, P = .086). CONCLUSIONS: This study showed that carotid IMT/plaque thickness was inversely related to the BMD in female but not in male patients with acute ischemic stroke. PMID- 26360325 TI - Participant roles in peer-victimization among young children in South Korea: Peer , self-, and teacher-nominations. AB - This study explored participant roles in aggressive behavior among 95 children aged five to seven years, in a collectivistic culture, South Korea. Using a short term longitudinal design, three types of nomination (peer, self, and teacher) were obtained for four participant roles (aggressor, victim, defender-stop, and defender-tell) and for four types of aggression (physical, verbal, social exclusion and rumor spreading). Assessments were made of stability of participant roles over time; inter-rater concordance among informants; discriminability; and relationships with sex, and likeability. Children tended to report themselves as victim and their peers as aggressors, especially for social exclusion. Nominations for aggressor showed highest stability over time and inter-rater concordance. Social exclusion showed different characteristics from other types of aggressive behavior in terms of its frequency and inter-rater concordance of role nominations. The type of defender (defender-stop or defender-tell) had different correlates with likeability. Findings are discussed in relation to different perspectives on social exclusion, and the defender role. Some different findings related specifically to social exclusion may be related to the particular nature of aggression or wang-ta in South Korea. PMID- 26360326 TI - Conservation of Planar Polarity Pathway Function Across the Animal Kingdom. AB - Planar polarity is a well-studied phenomenon resulting in the directional coordination of cells in the plane of a tissue. In invertebrates and vertebrates, planar polarity is established and maintained by the largely independent core and Fat/Dachsous/Four-jointed (Ft-Ds-Fj) pathways. Loss of function of these pathways can result in a wide range of developmental or cellular defects, including failure of gastrulation and problems with placement and function of cilia. This review discusses the conservation of these pathways across the animal kingdom. The lack of vital core pathway components in basal metazoans suggests that the core planar polarity pathway evolved shortly after, but not necessarily alongside, the emergence of multicellularity. PMID- 26360327 TI - Effects of the Surface Densities of Glycoclusters on the Determination of Their IC50 and Kd Value Determination by Using a Microarray. AB - Pseudomonas aeruginosa (PA) is an opportunistic bacterium involved in 10-30% of nosocomial diseases. It causes severe lung injury to cystic fibrosis patients, often leading to patient death. PA strains are multidrug resistant, thus making the design of new therapeutics a challenge for public health. One promising therapeutic option is to design glycoclusters that target the virulence factor of PA. LecA is a galactose-specific lectin that might be involved in adhesion and biofilm formation by PA. The DNA-directed immobilization (DDI) microarray is a powerful tool for screening and understanding of structure-activity relationships between glycoclusters and lectins. High-throughput and multiplexed analysis of lectin-glycocluster interactions on a DDI microarray allows measurement of IC50 and dissociation constant (Kd ) values with minute amounts of material. In order to study the robustness of the DDI microarray in determination of IC50 and Kd values, the impact of glycocluster surface density was investigated. The data obtained show that measured IC50 values were influenced by glycocluster surface density: as the density of glycoclusters increases, the measured IC50 values increase too. In contrast, the measured Kd values were not affected by glycocluster surface density, provided that the experimental conditions allow interaction between glycocluster and lectin at single-molecule level (no surface cluster effect). PMID- 26360328 TI - The Peptidome of Behcet's Disease-Associated HLA-B*51:01 Includes Two Subpeptidomes Differentially Shaped by Endoplasmic Reticulum Aminopeptidase 1. AB - OBJECTIVE: To characterize the peptidome of the Behcet's disease-associated HLA B*51:01 allotype as well as the differential features of major peptide subsets and their distinct endoplasmic reticulum aminopeptidase 1 (ERAP-1)-mediated processing. METHODS: The endogenous B*51:01-bound peptidome was characterized from 721.221 transfectant cells, after affinity chromatography and acid extraction, by tandem mass spectrometry. Recombinant ERAP-1 variants were used to digest synthetic B*51:01 ligands. HLA and transporter associated with antigen processing (TAP) binding affinities of peptide ligands were calculated with well established algorithms. ERAP-1 and ERAP-2 from 721.221 cells were characterized by genomic sequencing and Western blotting. RESULTS: The B*51:01 peptidome consisted of 29.5% octamers, 61.7% nonamers, 4.8% decamers, and 4.0% longer peptides. The major peptide motif consisted of Pro and Ala at position 2, aliphatic/aromatic position 3 residues, and Val and Ile at the C-terminal position. The ligands with Pro or Ala at position 2 constituted 2 distinct subpeptidomes. Peptides with Pro at position 2 showed higher affinity for B*51:01 and lower affinity for TAP than those with Ala at position 2. Most important, both peptide subsets differed drastically in the susceptibility of their position 1 residues to ERAP-1, revealing a distinct influence of this enzyme on both subpeptidomes, which may alter their balance, affecting the global affinity of B*51:01-peptide complexes. CONCLUSION: ERAP-1 has a significant influence on the B*51:01 peptidome and its affinity. This influence is based on very distinct effects on the 2 subpeptidomes, whereby only peptides in the subpeptidome with Ala at position 2 are extensively destroyed, except when their position 1 residues are ERAP-1 resistant. This pattern provides a mechanism for the epistatic association of ERAP-1 and B*51:01 in Behcet's disease. PMID- 26360330 TI - Comparison of dppf-Supported Nickel Precatalysts for the Suzuki-Miyaura Reaction: The Observation and Activity of Nickel(I). AB - Ni-based precatalysts for the Suzuki-Miyaura reaction have potential chemical and economic advantages compared to commonly used Pd systems. Here, we compare Ni precatalysts for the Suzuki-Miyaura reaction supported by the dppf ligand in 3 oxidation states, 0, I and II. Surprisingly, at 80 degrees C they give similar catalytic activity, with all systems generating significant amounts of Ni(I) during the reaction. At room temperature a readily accessible bench-stable Ni(II) precatalyst is highly active and can couple synthetically important heterocyclic substrates. Our work conclusively establishes that Ni(I) species are relevant in reactions typically proposed to involve exclusively Ni(0) and Ni(II) complexes. PMID- 26360329 TI - Association of TLR4 polymorphisms with Mycobacterium avium subspecies paratuberculosis infection status in Canadian Holsteins. AB - Mycobacterium avium ssp. paratuberculosis (MAP) causes chronic enteritis in cattle that results in substantial financial losses to the cattle industry worldwide. Given that susceptibility to MAP infection is determined in part by genetics, marker-assisted selection may help in the breeding of animals that are more resistant to MAP infection. The toll-like receptor 4 gene (TLR4) was selected as a potential candidate gene because of its role in innate immunity and its involvement in MAP recognition and infection. The objective of this study, therefore, was to identify associations between TLR4 polymorphisms and susceptibility to MAP infection in Canadian Holstein cows. Two biologically relevant SNPs, including c.-226G>C in the 5'-untranslated region and the non synonymous SNP c.2021C>T in the potential TIR domain, were selected for an association analysis with MAP infection status in 409 Canadian Holsteins. The haplotype C-T from these combined SNPs yielded significant association with susceptibility to MAP infection, supporting the involvement of TLR4 in susceptibility to MAP infection. PMID- 26360332 TI - Self-Sustained Resistance to Suppression of CD8+ Teff Cells at the Site of Autoimmune Inflammation Can Be Reversed by Tumor Necrosis Factor and Interferon gamma Blockade. AB - OBJECTIVE: Resistance of Teff cells to Treg cell-mediated suppression contributes to the breakdown of peripheral tolerance in the inflamed joints of patients with juvenile idiopathic arthritis (JIA). However, unanswered questions are whether this resistant phenotype is self-sustained and whether CD8+ and CD4+ Teff cells share the same mechanism of resistance to suppression. We undertook this study to investigate intrinsic resistance of CD8+ Teff cells to suppression and to determine how this can be targeted therapeutically. METHODS: CD8+ or CD4+ Teff cells were cultured with or without antigen-presenting cells (APCs) in Treg cell dependent and -independent suppression assays. Synovial fluid (SF)-derived Teff cells were crosscultured with peripheral blood (PB) Treg cells from JIA patients or healthy controls. Tumor necrosis factor (TNF) or interferon-gamma (IFNgamma) blocking agents were used to restore Teff cell responsiveness to suppression. RESULTS: Suppression of cell proliferation and cytokine production in CD8+ Teff cells from the SF of JIA patients was severely impaired compared to that in CD8+ Teff cells from the PB of JIA patients, regardless of the presence of APCs and CD4+ Teff cells. Similar to CD4+ Teff cells, impaired suppression of CD8+ Teff cells was shown to be an intrinsic feature of this cell population. While TNF blockade restored both CD8+ and CD4+ Teff cell susceptibility to suppression, autocrine release of IFNgamma selectively sustained CD8+ Teff cell resistance, which could be relieved by IFNgamma blockade. CONCLUSION: Unlike CD4+ Teff cells, resistance of CD8+ Teff cells to suppression at the site of autoimmune inflammation is maintained by autocrine release of IFNgamma, and blockade of IFNgamma restores CD8+ Teff cell responsiveness to suppression. These findings indicate a potential therapeutic value of blocking IFNgamma to restore immune regulation in JIA. PMID- 26360331 TI - The cost effectiveness of rotavirus vaccination in Iran. AB - Rotavirus is the most common cause of severe diarrhea leading to hospitalization or disease-specific death among young children. Effective vaccines have recently been approved and successful vaccination program implemented. The aim of this study was to evaluate the cost effectiveness of mass rotavirus vaccination program in Iran. We developed a Markov model that reflects key features of rotavirus natural history. Parameters of the model were assessed by field study or developed through literature search and published data. We applied the model to the 2009 Iranian birth cohort and evaluated the cost-effectiveness of including the rotavirus vaccine (Rotarix(r)) into Iranian expanded immunization program (EPI). With an estimated hospitalization rate of 0.05 and outpatient rate of 0.23 cases per person-year, vaccinating cohort of 1231735 infants in Iran with 2 doses of (Rotarix(r)), would prevent 32092 hospitalizations, 158750 outpatient visits, and 1591 deaths during 5 y of follow-up. Under base-case assumption of $10 cost per course of vaccine, the vaccination would incur an extra cost of $1,019,192 from health care perspective and would avert 54680 DALYs. From societal perspective, there would be $15,192,568 saving for the society with the same averted DALYs. The incremental cost effectiveness ratio showed a cost of $19 US dollars per averted DALY from health care perspective and a saving of $278 US dollars for each averted DALY from societal perspective. Introducing rotavirus vaccine into EPI program would be highly cost-effective public health intervention in Iran. PMID- 26360333 TI - Discovery of an intermolecular disulfide bond required for the thermostability of a heterodimeric protein from the thermophile Hydrogenobacter thermophilus. AB - Factors that increase protein thermostability are of considerable interest in both scientific and industrial fields. Disulfide bonds are one of such factors that increase thermostability, but are rarely found in intracellular proteins because of the reducing environment of the cytosol. Here, we report the first example of an intermolecular disulfide bond between heteromeric subunits of a novel-type phosphoserine phosphatase from a thermophilic bacterium Hydrogenobacter thermophilus, which contributes to the protein thermostability at the physiological temperature. Comparison of remaining soluble proteins between wild-type and cysteine-deleted mutant using SDS-PAGE revealed that the disulfide bond increases the thermostability of the whole protein by tightly connecting a subunit with low solubility to the partner with higher solubility. Furthermore, it was strongly suggested that the disulfide bond is formed and contributes to the stability in vivo. This finding will open new avenues for the design of proteins with increased thermostability. PMID- 26360335 TI - Prevalence and sociodemographic characteristics of self-reported suicidal behaviours in Latvia in 2010: A population-based study. AB - BACKGROUND: The fact that Latvia is among the countries with the highest suicide mortality rates in the European Union highlights the importance of research in this field. AIMS: The aims of the study were to determine the 2010 prevalence of self-reported suicidal behaviours in Latvia, to identify sociodemographic risk factors and to examine sequences for reporting of suicidal behaviours. METHODS: Computer assisted personal interviews were carried out to gather information on a representative sample of the Latvian population aged 18 to 64 (n = 2816). The study sample was selected using a combination of stratified random sampling and quota methods. RESULTS: Last year prevalence of any type of suicidal behaviour was 18.5% - nearly threefold lower than observed in 2000 (52.6%). Middle age, non cohabitation status and lower level of education were significant risk factors for serious types of suicidal behaviour (suicidal ideation, suicidal plans, suicide attempts) among men, but only lower level of education was for women. Risk factors regarding mild types of suicidal behaviour (life-weariness, death wishes) were the same for men and women: older and middle aged, non-cohabitation status, and lower level of education. A total of 79.6% reported a continuous pattern of suicidal behaviours. CONCLUSIONS: Several sociodemographic risk factors for suicidal behaviours have been found. Further research is needed to clarify additional risk factors, especially in the high-risk groups studied and specific determinants contributing to reduction in prevalence of suicidal behaviours and suicide mortality in Latvia. PMID- 26360336 TI - Shooting for Safety. AB - Austin Regional Clinic announced in June that it would no longer accept new pediatric patients whose parents or guardians don't permit vaccinations. The new policy aims to protect the clinic's most vulnerable patients, such as infants who aren't fully vaccinated, seniors, those who have compromised immune systems, and pregnant women. An exception is included for patients who have adverse reactions to vaccines or severely compromised immune systems. PMID- 26360337 TI - Farewell to 40 Years of Service. AB - The impending implementation of the ICD-10 coding system and burdensome regulations spur Austin Internal Medicine Associates to close its doors on Sept. 4, ending 40 years of service and more than 20 years together for its internists Ace Alsup, MD; Isabel Hoverman, MD; R. Scott Ream, MD; and Frank Robinson, MD. The group set its closing date to avoid anticipated technical difficulties - specifically, the Centers for Medicare and Medicaid Services' requirement that all practices switch to the controversial ICD-10 medical billing and coding system on Oct. 1. PMID- 26360334 TI - Ambrisentan and Tadalafil Up-front Combination Therapy in Scleroderma-associated Pulmonary Arterial Hypertension. AB - BACKGROUND: Scleroderma-associated pulmonary arterial hypertension (SSc-PAH) is a rare disease characterized by a very dismal response to therapy and poor survival. We assessed the effects of up-front combination PAH therapy in patients with SSc-PAH. METHODS: In this prospective, multicenter, open-label trial, 24 treatment-naive patients with SSc-PAH received ambrisentan 10 mg and tadalafil 40 mg daily for 36 weeks. Functional, hemodynamic, and imaging (cardiac magnetic resonance imaging and echocardiography) assessments at baseline and 36 weeks included changes in right ventricular (RV) mass and pulmonary vascular resistance as co-primary endpoints and stroke volume/pulmonary pulse pressure ratio, tricuspid annular plane systolic excursion, 6-minute walk distance, and N terminal pro-brain natriuretic peptide as secondary endpoints. RESULTS: At 36 weeks, we found that treatment had resulted in significant reductions in median (interquartile range [IQR]) RV mass (28.0 g [IQR, 20.6-32.9] vs. 32.5 g [IQR, 23.2-41.4]; P < 0.05) and median pulmonary vascular resistance (3.1 Wood units [IQR, 2.0-5.7] vs. 6.9 Wood units [IQR, 4.0-12.9]; P < 0.0001) and in improvements in median stroke volume/pulmonary pulse pressure ratio (2.6 ml/mm Hg [IQR, 1.8-3.5] vs. 1.4 ml/mm Hg [IQR 8.9-2.4]; P < 0.0001) and mean ( +/- SD) tricuspid annular plane systolic excursion (2.2 +/- 0.12 cm vs. 1.65 +/- 0.11 cm; P < 0.0001), 6-minute walk distance (395 +/- 99 m vs. 343 +/- 131 m; P = 0.001), and serum N-terminal pro-brain natriuretic peptide (647 +/- 1,127 pg/ml vs. 1,578 +/- 2,647 pg/ml; P < 0.05). CONCLUSIONS: Up-front combination therapy with ambrisentan and tadalafil significantly improved hemodynamics, RV structure and function, and functional status in treatment-naive patients with SSc-PAH and may represent a very effective therapy for this patient population. In addition, we identified novel hemodynamic and imaging biomarkers that could have potential value in future clinical trials. Clinical trial registered with www.clinicaltrials.gov (NCT01042158). PMID- 26360338 TI - Better Bridges, Better Systems. AB - An electronic health record (EHR) research project illustrates the need for physicians to get involved in usability testing to help vendors improve their products. Some of the research centered on testing EHR systems for usability and interviewing EHR vendors about their capabilities to build systems tailored to the needs of the user. The usability testing of commercial EHRs largely confirmed what many physicians report from their own experience: EHR systems are often difficult to use and hinder patient care in a clinical setting. PMID- 26360339 TI - Medicare Pays for Chronic Care Management. AB - As of January, the Centers for Medicare & Medicaid Services began paying for chronic care management of patients with two or more conditions under its Chronic Care Management program. The payment applies to patients in traditional fee-for service and noncapitated Medicare Advantage plan arrangements. Texas Medical Association leaders caution the program has some hefty requirements. PMID- 26360340 TI - Regs and Pains. AB - Newly adopted changes to the Texas Medical Board's pain management rules turn numerous chronic pain treatment guidelines into minimum requirements. The stricter rules prompt liability concerns as the board strives to ensure patients receive treatment that matches the evolving standard of care. PMID- 26360341 TI - SGR Is Gone. Now What? AB - Physicians will have to prepare to participate in one of the new payment systems that will replace Medicare's Sustainable Growth Rate formula, which Congress eliminated in April via the Medicare and CHIP Reauthorization Act. Come 2019, physicians can participate in one of two major payment tracks: the fee-for service Merit-Based Incentive Payment System, which boosts or docks physician pay based on their quality and cost performance; or one or more alternative payment models, such as accountable care organizations, medical homes, bundled payments, or other initiatives. PMID- 26360342 TI - Magnetic Nanocomposite Hydrogel for Potential Cartilage Tissue Engineering: Synthesis, Characterization, and Cytocompatibility with Bone Marrow Derived Mesenchymal Stem Cells. AB - Hydrogels possess high water content and closely mimic the microenvironment of extracellular matrix. In this study, we created a hybrid hydrogel containing type II collagen, hyaluronic acid (HA), and polyethylene glycol (PEG) and incorporated magnetic nanoparticles into the hybrid hydrogels of type II collagen-HA-PEG to produce a magnetic nanocomposite hydrogel (MagGel) for cartilage tissue engineering. The results showed that both the MagGel and hybrid gel (Gel) were successfully cross-linked and the MagGel responded to an external magnet while maintaining structural integrity. That is, the MagGel could travel to the tissue defect sites in physiological fluids under remote magnetic guidance. The adhesion density of bone marrow derived mesenchymal stem cells (BMSCs) on the MagGel group in vitro was similar to the control group and greater than the Gel group. The morphology of BMSCs was normal and consistent in all groups. We also found that BMSCs engulfed magnetic nanoparticles in culture and the presence of magnetic nanoparticles did not affect BMSC adhesion and morphology. We hypothesized that the ingested nanoparticles may be eventually broken down by lysosome and excreted through exocytosis; further studies are necessary to confirm this. This study reports a promising magnetic responsive nanocomposite hydrogel for potential cartilage tissue engineering applications, which should be further studied for its effects on cell functions when combined with electromagnetic stimulation. PMID- 26360343 TI - Improving the yield of psychotherapy research. AB - OBJECTIVE: Although the effectiveness of psychotherapy is well documented, little progress has been made in elucidating mechanisms of change. Major impediments to progress are the homogeneity assumptions evident in many psychotherapy studies. Case-specific research strategies avoid treating patients, therapists, and treatments as homogeneous variables and such studies are more successful at elucidating the link between psychotherapy processes and treatment outcome. METHOD: A case-specific, process-outcome study comprised of 39 patients treated by experienced therapists is presented. We did not focus on a supposedly homogeneous diagnostic group of patients (e.g., depressed patients) or particular manualized brands of therapy. Instead, we identified each patient's particular problems and conflicts (plan formulation) and then determined the degree to which therapists effectively addressed the patient's problems-that is, the degree to which therapists' interventions were compatible with (i.e., responsive to) the patient's plan. RESULTS: Correlations between ratings of therapist responsiveness (plan compatibility of interventions) and a variety of outcome assessments were significant and substantial (accounting on average for 25% of outcome variance). CONCLUSION: The findings presented here suggest that the extent to which therapists are responsive to their patients' plans is a strong predictor of treatment outcome and of patients feeling positively about their therapy experience. PMID- 26360344 TI - Surface-coated probe nanoelectrospray ionization mass spectrometry for analysis of target compounds in individual small organisms. AB - Analysis of target compounds in individual small organisms is of significant importance for biological, environmental, medicinal, and toxicological investigation. In this study, we reported the development of a novel solid-phase microextraction (SPME) based ambient mass spectrometry (MS) method named surface coated probe nanoelectrospray ionization (SCP-nanoESI)-MS for analysis of target compounds in individual small organisms with sizes at micrometer-to-millimeter level. SCP-nanoESI-MS analysis involves three procedures: (1) modification of adsorbent at the surface of a fine metal probe to form a specially designed surface-coated SPME probe with probe-end diameter at several-micrometer level, (2) application of the surface-coated SPME probe for enrichment of target analytes from individual small organisms, and (3) employment of a nanospray tip and some solvent to desorb the analytes and induce nanoESI for mass spectrometric analysis under ambient condition. A SCP-nanoESI-MS method for determination of the perfluorinated compounds (PFCs) in individual Daphnia magna was developed. The method showed satisfactory linearities for analysis of real Daphnia magna samples, with correlation coefficient values (R(2)) of 0.9984 and 0.9956 for perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA), respectively. The limits of detection were 0.02 and 0.03 ng/mL for PFOS and PFOA, respectively. By using the proposed method, the amount, bioaccumulation kinetics, and distribution of PFOS and PFOA in individual Daphnia magna were successfully investigated. PMID- 26360345 TI - Switchable Reconfiguration of a Seven-Ring Interlocked DNA Catenane Nanostructure. AB - The synthesis, purification, and structure characterization of a seven-ring interlocked DNA catenane is described. The design of the seven-ring catenane allows the dynamic reconfiguration of any of the four rings (R1, R3, R4, and R6) on the catenane scaffold, or the simultaneous switching of any combination of two, three, or all four rings to yield 16 different isomeric states of the catenane. The dynamic reconfiguration across the states is achieved by implementing the strand-displacement process in the presence of appropriate fuel/antifuel strands and is probed by fluorescence spectroscopy. Each of the 16 isomers of the catenane can be transformed into any of the other isomers, thus allowing for 240 dynamic transitions within the system. PMID- 26360346 TI - Highly robust hydrogels via a fast, simple and cytocompatible dual crosslinking based process. AB - A highly robust hydrogel device made from a single biopolymer formulation is reported. Owing to the presence of covalent and non-covalent crosslinks, these engineered systems were able to (i) sustain a compressive strength of ca. 20 MPa, (ii) quickly recover upon unloading, and (iii) encapsulate cells with high viability rates. PMID- 26360347 TI - Frostbite: A Novel Presentation of Glucose-6-Phosphate Dehydrogenase Deficiency? AB - Acute hemolytic anemia (AHA) due to glucose 6-phosphate dehydrogenase (G6PD) deficiency has rarely been recognized as a contributor to the development of frostbite. We discuss a case of frostbite in a 32-year-old male Marine with G6PD deficiency during military training on Mount McKinley in Alaska, which eventually led to a permanent disability. In this report, the pathophysiology of G6PD deficiency, the effects of hemolytic anemia, and factors that contribute to frostbite will be discussed, as well as the clinical findings, treatment course, and the outcome of this case. The patient was evacuated and admitted to Alaska Regional Hospital. He was treated for fourth-degree frostbite, ultimately resulting in the complete or partial amputation of all toes. Although it cannot be proved that AHA occurred in this patient, this case potentially adds frostbite to the list of rare but possible clinical presentations of G6PD deficiency. PMID- 26360348 TI - Evaluation for Testosterone Deficiency. AB - There has been a recent increase in the number of Operators presenting to clinics for evaluation of possible low testosterone. In response, USASOC recently released an Androgen Deficiency Clinical Practice Guideline (CPG) to help guide providers through the initial evaluation and treatment of patients. The diagnosis of hypogonadism is based on consistent signs and symptoms of androgen deficiency and unequivocally low serum testosterone (below 300 ng/dL). Testosterone levels can change for a variety of reasons and an adequate evaluation requires multiple laboratory tests over a period of time. If a diagnosis of hypogonadism is confirmed, differentiating between primary and secondary hypogonadism can help guide further care. Testosterone replacement therapy options are available, but careful monitoring for side-effects is required. Controversy still exists surrounding the safety of testosterone replacement therapy, and referral to endocrinology should strongly be considered before initiating treatment. PMID- 26360349 TI - Emergency Cricothyroidotomy in Tactical Combat Casualty Care. PMID- 26360350 TI - Junctional Tourniquet Training Experience. AB - Since 2009, out-of-hospital care of junctional hemorrhage bleeding from the trunk appendage junctions has changed, in part, due to the newly available junctional tourniquets (JTs) that have been cleared by the US Food and Drug Administration. Given four new models of JT available in 2014, several military services have begun to acquire, train, or even use such JTs in care. The ability of users to be trained in JT use has been observed by multiple instructors. The experience of such instructors has been broad as a group, but their experience as individuals has been neither long nor deep. A gathering into one source of the collective experience of trainers of JT users could permit a collation of useful information to include lessons learned, tips in skill performance, identification of pitfalls of use to avoid, and strategies to optimize user learning. The purpose of the present review is to record the experiences of several medical personnel in their JT training of users to provide a guide for future trainers. PMID- 26360351 TI - The Operational Canine and K9 Tactical Emergency Casualty Care Initiative. AB - BACKGROUND: Approximately 20% to 25% of trauma-related, prehospital fatalities in humans are due to preventable deaths. Data are lacking, however, on the nature and the prevalence of operational canine (OC) prehospital deaths. It is plausible that OCs engaged in high-threat operations are also at risk for suffering some type of preventable death. Tactical Combat Casualty Care has significantly reduced human fatality rates on the battlefield. Standardized guidelines specifically for prehospital trauma care have not been developed for the OC caregiver. An initiation has been approved by the Committee for Tactical Emergency Casualty Care to form a K9-Tactical Emergency Casualty Care (TECC) working group to develop such guidelines. SIGNIFICANCE: The intent of the K9-TECC initiative is to form best practice recommendations for the civilian high-risk OC caregiver. These recommendations are to focus on interventions that (1) eliminate the major causes of canine out-of-hospital preventable deaths, (2) are easily learned and applied by any civilian first responder, and (2) minimize resource consumption. PMID- 26360352 TI - Conceptualized Use of Self-Expanding Foam to Rescue Special Operators From Abdominal Exsanguination: Percutaneous Damage Control for the Forward Deployed. AB - BACKGROUND: Noncompressible hemorrhage is the leading cause of potentially survivable death on the battlefield. In Special Operations Forces (SOF), 50% of potentially survivable deaths have been related to noncompressible hemorrhage. Currently, there are no widely available presurgical interventions that can slow abdominal bleeding. Consequently, many of the preventable deaths occur en route to definitive care as a failure to rescue from exsanguination. A self-expanding polyurethane foam has been developed as a percutaneous damage control intervention to rescue casualties who would otherwise die of noncompressible hemorrhage, and allow them to survive long enough to reach surgical intervention. The purpose of this paper is to summarize the existing preclinical data, describe the role of SOF personnel in foam delivery-system development, and to integrate these together to conceptualize how foam could be incorporated into SOF medical care. METHODS: All existing publications on self-expanding foam are reviewed. Additionally, eight SOF medical providers with combat experience provided end user input to delivery-device design through an interactive human-factors testing process. RESULTS: Ten preclinical publications described efficacy, safety, dose translation, and risk-benefit analysis of exsanguination rescue with percutaneous foam damage control. SOF medical providers guided weight, cubic, operational requirements, and limits for the foam delivery device. CONCLUSION: Presurgical exsanguination rescue with percutaneous foam damage control is safe and effective with a favorable risk-benefit profile in preclinical studies. Battlefield, presurgical use by SOF medical providers is conceptually possible. Adoption of the technology on the battlefield should proceed with SOF medical provider input. PMID- 26360353 TI - The Ranger First Responder Program and Tactical Emergency Casualty Care Implementation: A Whole-Community Approach to Reducing Mortality From Active Violent Incidents. AB - Active violent incidents are dynamic and challenging situations that can produce a significant amount of preventable deaths. Lessons learned from the military?s experience in Afghanistan and Iraq through the Committee on Tactical Combat Casualty Care and the 75th Ranger Regiment?s Ranger First Responder Program have helped create the Committee for Tactical Emergency Casualty Care (C-TECC) to address the uniqueness of similar wounding patterns and to end preventable deaths. We propose a whole-community approach to active violent incidents, using the C-TECC Trauma Chain of Survival and a tiered approach for training and responsibilities: the first care provider, nonmedical professional first responders, medical first responders, and physicians and trauma surgeons. The different tiers are critical early links in the Chain of Survival and this approach will have a significant impact on active violent incidents. PMID- 26360354 TI - Kitona 2013: A Medical Readiness Training Exercise in the Democratic Republic of the Congo Leading to Lion Rouge. AB - BACKGROUND: Health initiatives support regional stability and are a priority for US and African partners. We present data and experience from the Democratic Republic of Congo (DRC), a strategically and epidemiologically ideal location for collaborative medical engagement (CME). Our objectives included relationship building, exposure of US military medical personnel to uncommon tropical diseases, bolstering a referral hospital, and updating Congolese physicians on new treatment or preventive standards of care. METHODS: We conducted a CME-styled medical readiness training exercise (MEDRETE) at the Military Referral Hospital of Kitona in June 2013. US and Congolese healthcare providers presented 20 lectures and evaluated 158 patients collaboratively; 132 for infections. RESULTS: The CME led to Lion Rouge, the first joint military, multidisciplinary engagement between the respective militaries. Equally noteworthy is that some of the same participants returned to the same location for the follow-on exercise, providing continuity. CONCLUSION: These outcomes suggest the MEDRETE and CME approaches were successful. PMID- 26360355 TI - What Is the Optimal Device Length and Insertion Site for Needle Thoracostomy in UK Military Casualties? A Computed Tomography Study. AB - Significant lessons to inform best practice in trauma care should be learned from the last decade of conflict in Afghanistan and Iraq. This study used radiological data collated in the UK Military Hospital in Camp Bastion, Afghanistan, to investigate the most appropriate device length for needle chest decompression of tension pneumothorax (TP). We reviewed the optimal length of device and site needed for needle decompression of a tension pneumothorax in a UK military population and found no significant difference between sites for needle chest decompression (NCD). As a result, we do not recommend use of devices longer than 60mm for UK service personnel. PMID- 26360356 TI - Associations Among Back and Extremity Pain With Alcohol, Tobacco, and Caffeine Use Among US Air Force Pararescuemen. AB - BACKGROUND: Caffeine, tobacco, and alcohol are the most widely used substances globally, but the majority of research on the associations among legal substance use and physical health has focused on the general population, not elite military personnel. The purpose of the current study was to describe patterns of tobacco, alcohol, and caffeine use and to examine the relationship of legal substance use with self-reported physical health complaints among US Air Force Pararescuemen (PJs) and Combat Rescue Officers (CROs). METHODS: Participants were 196 US PJs and CROs. Participants completed self-report measures of legal drug use and somatic symptoms. Generalized linear modeling with robust maximum likelihood estimation was used for multivariate regression analyses. Chi-square analyses were conducted for univariate comparisons of categorical variables. RESULTS: Reported rates of tobacco use (28.2%), alcohol consumption (83.2%), and regular caffeine consumption (88.8%) were similar to the general population. Daily caffeine intake was significantly higher among participants reporting they were bothered a lot by back pain [Wald chi2(2)=11.39; rho=.003] and extremity pain [Wald chi2(2)=11.39; rho=.003], even when controlling for age and deployment history. Participants with severe extremity pain also reported drinking approximately twice as many alcoholic beverages per week (mean, 5.46; standard error [SE], 0.91) than participants who were bothered a little (mean, 2.88; SE, 0.54) or not bothered at all (mean, 2.88; SE, 0.52) by extremity pain. CONCLUSION: Back and extremity pain is associated with greater caffeine and alcohol consumption among PJs. PMID- 26360357 TI - Resuscitation During Critical Care Transportation in Afghanistan. AB - OBJECTIVE: These data describe the critical care procedures performed on, and the resuscitation markers of, critically wounded personnel in Afghanistan following point of injury (POI) transports and intratheater transports. Providing this information may help inform discussion on the design of critical care transportation platforms for future conflicts. METHODS: The Department of Defense Trauma Registry (DoDTR) was queried for descriptive data on combat casualties with Injury Severity Score (ISS) greater than 15 who were transported in Operation Enduring Freedom (OEF) from 1 January 2010 to 31 December 2010. Both POI transportation events and interfacility transportation events were reviewed. Base deficit (BD) was evaluated as a maker of resuscitation, and international normalized ratio (INR) was evaluated as a measure of coagulopathy. RESULTS: There were 1198 transportation events that occurred during the study period--634 (53%) transports from the POI and 564 (47%) intratheater transports. Critical care interventions were performed during 147 (12.3%) transportation events, including intubation, cricothyrotomy, double-lumen endotracheal tube placement, needle or tube thoracostomy, central venous access placement, and cardiopulmonary resuscitation. The mean BD on arrival in the emergency department was -5.4 mEq/L for POI transports and 0.68 mEq/L intratheater transports (rho<.001). The mean INR on arrival in the emergency department was 1.48 for POI transports and 1.21 for intratheater transports (rho<.001). CONCLUSIONS: Critical care interventions were needed frequently during evacuation of severely injured personnel. Furthermore, many troops arrived acidotic and coagulopathic following initial transport from POI. Together, these data suggest that a platform capable of damage control resuscitation and critical care interventions may be warranted on longer transports of more critically injured patients. PMID- 26360358 TI - Prolonged Field Care Working Group Position Paper: Prolonged Field Care Capabilities. PMID- 26360359 TI - Prolonged Field Care Working Group Position Paper: Operational Context for Prolonged Field Care. PMID- 26360360 TI - Tourniquet Conversion: A Recommended Approach in the Prolonged Field Care Setting. AB - Life-saving interventions take precedence over diagnostic maneuvers in the Care Under Fire stage of Tactical Combat Casualty Care. The immediate threat to life with an actively hemorrhaging extremity injury is addressed with the liberal and proper use of tourniquets. The emphasis on hemorrhage control has and will continue to result in the application of tourniquets that may not be needed past the Care Under Fire stage. As soon as tactically allowable, all tourniquets must be reassessed for conversion. Reassessment of all tourniquets should occur as soon as the tactical situation permits, but no more than 2 hours after initial placement. This article describes a procedure for qualified and trained medical personnel to safely convert extremity tourniquets to local wound dressings, using a systematic process in the field setting. PMID- 26360361 TI - Care of the Burn Casualty in the Prolonged Field Care Environment. AB - Burns are frequently encountered on the modern battlefield, with 5% - 20% of combat casualties expected to sustain some burn injury. Addressing immediate life threatening conditions in accordance with the MARCH protocol (massive hemorrhage, airway, respirations, circulation, hypothermia/head injury) remains the top priority for burn casualties. Stopping the burning process, total burn surface area (TBSA) calculation, fluid resuscitation, covering the wounds, and hypothermia management are the next steps. If transport to definitive care is delayed and the prolonged field care stage is entered, the provider must be prepared to provide for the complex resuscitation and wound care needs of a critically ill burn casualty. PMID- 26360362 TI - Journal Club: Ketamine in the Emergency Department. PMID- 26360363 TI - Androgens and Androgen Derivatives: Science, Myths, and Theories: Explored From a Special Operations Perspective. AB - Androgen use outside of legitimate medical therapy is a perceived concern that is drawing attention across military and specifically Special Operations Forces (SOF) communities. For leadership and the medical community to properly address the issue and relate to those individuals who are using or considering use, it will be crucial to understand the scope of the problem. Limited data suggest that the prevalence of androgen use may be increasing, and inferences made from the scientific literature suggest that SOF may be a population of concern. While risks of androgen use are well known, there are little data specific to military performance that can be applied to a rigorous risk:benefit analysis, allowing myths and poorly supported theories to perpetuate within the community. Further efforts to define the potential benefits balanced against the short- and long term risks should be undertaken. Providers within the SOF community should arm themselves with information to engage androgen users and leadership in meaningful discussion regarding androgen use. PMID- 26360364 TI - Rabies: 2015 Update. AB - Rabies is an almost universally fatal viral disease transmitted to humans primarily by bites and scratches from infected animals, and less commonly through other routes, including transplantation of infected organs, exposure to infected neural tissue, and possibly through airborne and aerosolized routes. This disease is endemic to all continents worldwide except Antarctica, and only a few islands elsewhere can be considered "rabies free." Special Operations Forces medical providers should be aware of this disease. Prevention and recognition of risk are key due to its extreme lethality. PMID- 26360365 TI - Extreme Conditioning Programs: Potential Benefits and Potential Risks. AB - CrossFit, Insanity, Gym Jones, and P90X are examples of extreme conditioning programs (ECPs). ECPs typically involve high-volume and high-intensity physical activities with short rest periods between movements and use of multiple joint exercises. Data on changes in fitness with ECPs are limited to CrossFit investigations that demonstrated improvements in muscle strength, muscular endurance, aerobic fitness, and body composition. However, no study has directly compared CrossFit or other ECPs to other more traditional forms of aerobic and resistance training within the same investigation. These direct comparisons are needed to more adequately evaluate the effectiveness of ECPs. Until these studies emerge, the comparisons with available literature suggest that improvements in CrossFit, in terms of muscular endurance (push-ups, sit-ups), strength, and aerobic capacity, appear to be similar to those seen in more traditional training programs. Investigations of injuries in ECPs are limited to two observational studies that suggest that the overall injury rate is similar to that seen in other exercise programs. Several cases of rhabdomyolysis and cervical carotid artery dissections have been reported during CrossFit training. The symptoms, diagnosis, and treatment of these are reviewed here. Until more data on ECPs emerge, physical training should be aligned with US Army doctrine. If ECPs are included in exercise programs, trainers should (1) have appropriate training certifications, (2) inspect exercise equipment regularly to assure safety, (3) introduce ECPs to new participants, (4) ensure medical clearance of Soldiers with special health problems before participation in ECPs, (4) tailor ECPs to the individual Soldier, (5) adjust rest periods to optimize recovery and reduce fatigue, (6) monitor Soldiers for signs of overtraining, rhabdomyolysis, and other problems, and (7) coordinate exercise programs with other unit training activities to eliminate redundant activities and minimize the risk of overuse injuries. PMID- 26360366 TI - This Is Africa. AB - Military deployments will always result in exposure to health hazards other than those from combat operations. The occupational and environmental health and endemic disease health risks are greater to the Special Operations Forces (SOF) deployed to the challenging conditions in Africa than elsewhere in the world. SOF are deployed to locations that lack life support infrastructures that have become standard for most military deployments; instead, they rely on local resources to sustain operations. Particularly, SOF in Africa do not generally have access to advanced diagnostic or monitoring capabilities or to medical treatment in austere locations that lack environmental or public health regulation. The keys to managing potential adverse health effects lie in identifying and documenting the health hazards and exposures, characterizing the associated risks, and communicating the risks to commanders, deployed personnel, and operational planners. PMID- 26360367 TI - Public Access Hemorrhage Control and the Stop the Bleeding Coalition. PMID- 26360368 TI - Dasatinib-related Follicular Hyperplasia: An Underrecognized Entity With Characteristic Morphology. AB - Dasatinib, a second-generation tyrosine kinase inhibitor with activity against BCR-ABL1 and other Src family tyrosine kinases, is approved as a first-line treatment option for Philadelphia chromosome-positive chronic myelogenous leukemia (CML) in the chronic phase. Recently, lymphadenopathy with morphologic features of reactive follicular hyperplasia was described in a cohort of patients with CML on long-term dasatinib therapy. However, the complete morphologic and immunophenotypic features of this previously underappreciated adverse effect have not been fully described. Herein, we report 3 cases of unexplained lymphadenopathy resulting in multiple diagnostic procedures in patients with CML and a history of long-term dasatinib therapy. Morphologic examination demonstrated preserved nodal architecture showing hybrid features of progressive transformation of germinal centers and Castleman-type changes in a background of florid follicular hyperplasia. Large germinal centers were disrupted by complex infolding of IgD+ mantle zones arranged as cuffs surrounding perforating capillaries. Other abnormalities variably present included decreased CD20 expression among polytypic B cells and increased Epstein-Barr virus reactivity in scattered paracortical cells and/or individual germinal centers. B-cell clonality studies showed no predominant clonal rearrangements. Consideration of dasatinib related lymphadenopathy may pre-empt unnecessary repeat diagnostic procedures in patients with CML or other dasatinib-susceptible malignancies and persistent lymphadenopathy. PMID- 26360369 TI - Management of Conductive Hearing Loss in Children. AB - Conductive hearing loss (CHL), far more common than sensorineural hearing loss in children, can be acquired or congenital, can range from mild to moderately severe, and can be caused by a simple cerumen impaction, middle ear fluid, or complex middle ear abnormalities with or without the absence of the ear canal (congenital aural atresia). This article presents evidence-based recommendations for the evaluation and management of the child with both acquired and congenital CHL. PMID- 26360370 TI - Modifiable Lifestyle Factors and Triple-negative Breast Cancer Survival: A Population-based Prospective Study. AB - BACKGROUND: Very little is known about the effect of modifiable lifestyle factors on outcomes of triple-negative breast cancer. We examined this association in a population-based prospective cohort study of patients with triple-negative breast cancer. METHODS: A total of 518 women with confirmed triple-negative breast cancer, recruited by the Shanghai Breast Cancer Survival Study, completed 6-, 18 , 36-, and 60-month postdiagnosis surveys. We applied Cox proportional hazard models to evaluate the associations. RESULTS: The mean age at diagnosis was 53.4 (standard deviation = 10.6) years old. After a median follow-up of 9.1 years (range: 0.6-11.8), 128 deaths and 112 recurrences were documented. Exercise during the first 60 months postdiagnosis was inversely associated with total mortality and recurrence/disease-specific mortality with adjusted hazard ratios (HRs) of 0.67 (95% confidence interval [CI] = 0.46, 0.96) and 0.58 (95% CI = 0.39, 0.86), respectively. Women with higher exercise-metabolic equivalent scores (>=7.6 metabolic equivalent-hours/week) and longer duration of exercise (>=2.5 hours/week) had lower risk of total and recurrence/disease-specific mortality than did nonexercisers. Compared with nontea drinkers, survival was better among women who were regular tea drinkers during the first 60 months for all cause (HR = 0.57, 95% CI = 0.34, 0.93) and recurrence/disease-specific mortality (HR = 0.54, 95% CI = 0.31, 0.96). There was no dose-response pattern for tea consumption. No interactions were observed for body mass index, menopausal status, and comorbidity. CONCLUSIONS: These findings show that postdiagnosis exercise and tea intake were associated with improved survival among women with triple-negative breast cancer. PMID- 26360371 TI - Maternal Folic Acid Supplementation During Pregnancy and Early Childhood Asthma. AB - BACKGROUND: Asthma is one of the most common chronic childhood diseases. While folic acid supplementation around conception helps prevent neural tube defects, an animal model suggests that it may be a risk factor for respiratory diseases, although epidemiologic studies have had conflicting results. We investigated the timing of folic acid-containing prescription filling during pregnancy and child asthma. METHODS: In a retrospective cohort study of 104,428 children, born 1996 2005, and their mothers enrolled in Tennessee Medicaid, we investigated the association of filling folic acid-containing prescriptions during pregnancy and childhood asthma at ages 4.5-6 years. We categorized women into exposure groups based on prescription filling centered around the first trimester: no folic acid prescription exposure, exposure in first trimester only, exposure after first trimester, and exposure in first trimester and beyond. We defined asthma using asthma-specific healthcare visits and medication fills. Using logistic regression models, we investigated the relationship adjusting for potential confounders. RESULTS: Overall 15% of children had asthma. Compared with children born to women with no folic acid prescription exposure, children born to women with exposures in the first trimester only or first trimester and later had increased relative odds of asthma (adjusted odds ratios = 1.2, 95% confidence interval = 1.1, 1.3, and 1.2, 95% confidence interval = 1.2, 1.3); no association was seen in children born to women exposed after the first trimester. CONCLUSION: Timing of folic acid containing prescription filling during pregnancy was associated with childhood asthma. Our findings contribute to understanding of the role of prenatal nutritional supplements on child respiratory health. PMID- 26360373 TI - Alterations in the NF2/LATS1/LATS2/YAP Pathway in Schwannomas. AB - Schwannomas are benign nerve sheath tumors composed of well-differentiated Schwann cells. Other than frequent NF2 (neurofibromatosis type 2) mutations (50% 60%), their molecular pathogenesis is not fully understood. LATS1 and LATS2 are downstream molecules of NF2 and are negative regulators of the yes-associated protein (YAP) oncogene in the Hippo signaling pathway. We assessed mutations of the NF2, LATS1, and LATS2 genes, promoter methylation of LATS1 and LATS2, and expression of YAP and phosphorylated YAP in 82 cases of sporadic schwannomas. Targeted sequencing using the Ion Torrent Proton instrument revealed NF2 mutations in 45 cases (55%), LATS1 mutations in 2 cases (2%), and LATS2 mutations in 1 case (1%) of schwannoma. Methylation-specific polymerase chain reaction showed promoter methylation of LATS1 and LATS2 in 14 cases (17%) and 25 cases (30%), respectively. Overall, 62 cases (76%) had at least 1 alteration in the NF2, LATS1, and/or LATS2 genes. Immunohistochemistry revealed nuclear YAP expression in 18 of 42 cases of schwannoma (43%) and reduced cytoplasmic phosphorylated YAP expression in 15 of 49 cases of schwannoma (31%), all of which had at least 1 alteration in the NF2, LATS1, and/or LATS2 genes. These results suggest that an abnormal Hippo signaling pathway is involved in the pathogenesis of most sporadic schwannomas. PMID- 26360372 TI - Application of a New Statistical Model for Measurement Error to the Evaluation of Dietary Self-report Instruments. AB - Most statistical methods that adjust analyses for dietary measurement error treat an individual's usual intake as a fixed quantity. However, usual intake, if defined as average intake over a few months, varies over time. We describe a model that accounts for such variation and for the proximity of biomarker measurements to self-reports within the framework of a meta-analysis, and apply it to the analysis of data on energy, protein, potassium, and sodium from a set of five large validation studies of dietary self-report instruments using recovery biomarkers as reference instruments. We show that this time-varying usual intake model fits the data better than the fixed usual intake assumption. Using this model, we estimated attenuation factors and correlations with true longer-term usual intake for single and multiple 24-hour dietary recalls (24HRs) and food frequency questionnaires (FFQs) and compared them with those obtained under the "fixed" method. Compared with the fixed method, the estimates using the time-varying model showed slightly larger values of the attenuation factor and correlation coefficient for FFQs and smaller values for 24HRs. In some cases, the difference between the fixed method estimate and the new estimate for multiple 24HRs was substantial. With the new method, while four 24HRs had higher estimated correlations with truth than a single FFQ for absolute intakes of protein, potassium, and sodium, for densities the correlations were approximately equal. Accounting for the time element in dietary validation is potentially important, and points toward the need for longer-term validation studies. PMID- 26360374 TI - Neuroinflammatory Gene Regulation, Mitochondrial Function, Oxidative Stress, and Brain Lipid Modifications With Disease Progression in Tau P301S Transgenic Mice as a Model of Frontotemporal Lobar Degeneration-Tau. AB - Tau P301S transgenic mice (PS19 line) are used as a model of frontotemporal lobar degeneration (FTLD)-tau. Behavioral alterations in these mice begin at approximately 4 months of age. We analyzed molecular changes related to disease progression in these mice. Hyperphosphorylated 4Rtau increased in neurons from 1 month of age in entorhinal and piriform cortices to the neocortex and other regions. A small percentage of neurons developed an abnormal tau conformation, tau truncation, and ubiquitination only at 9/10 months of age. Astrocytosis, microgliosis, and increased inflammatory cytokine and immune mediator expression also occurred at this late stage; hippocampi were the most markedly affected. Altered mitochondrial function, increased reactive oxygen species production, and limited protein oxidative damage were observed in advanced disease. Tau oligomers were only present in P301S mice, they were found in somatosensory cortex and hippocampi at the age of 3 months, and they increased across time in the somatosensory cortex and were higher and sustained in hippocampi. Age-related modifications in lipid composition occurred in both P301S and wild-type mice with regional and phenotypic differences; however, changes of total lipids did not seem to have pathogenic implications. Apoptosis only occurred in restricted regions in late disease. The complex tau pathology, mitochondrial alterations, oxidative stress damage, glial reactions, neuroinflammation, and cell death in P301S mice likely parallel those in FTLD-tau. Thus, therapies should focus first on abnormal tau rather than secondary events that appear late in the course of FTLD-tau. PMID- 26360375 TI - Ultrastructural Changes in the White and Gray Matter of Mice at Chronic Time Points After Repeated Concussive Head Injury. AB - Mild traumatic brain injury is a risk factor for neurodegenerative disease. We recently developed a model of repetitive concussive injury in mice that we have extensively characterized from 24 hours to 24 months after injury. Animals show evidence of progressive spatial memory deficits, thinning of the corpus callosum, axonal injury, and neuroglial activation. Here, we extended our neuropathologic characterization to the ultrastructural level in both a qualitative and a quantitative study. We focused on chronic (3 and 6 months) postinjury time points when the earliest stages of degenerative secondary changes were previously observed. In both C57BL/6 and hTau mice, we found white matter damage typified by axonal degeneration, microglial phagocytosis, and increased neuroglial cell density. In the cerebral cortex, we observed evidence of synaptic degeneration, dark neurons, altered dendritic microfilaments, subtle changes to the microvasculature, a mild augmentation of age-related features such as lipofuscin deposition, and electron-dense inclusions in microglial and perivascular cells. The majority of these ultrastructural features seemed to be more prominent at 3 versus 6 months after injury. Similar patterns were observed in C57BL/6 and hTau mice. These findings further support the relevance of our concussive injury model to the consequences of repetitive mild traumatic brain injury in humans. PMID- 26360376 TI - Patterns of Adenoma Recurrence in Familial Adenomatous Polyposis Patients after Ileal Pouch-Anal Anastomosis. AB - AIM: This study aims at identifying the risk factors for the development of pre cancerous pouch and/or cuff adenomas post ileal pouch anal anastomosis (IPAA) in familial adenomatous polyposis patients. METHOD: We retrospectively studied 59 patients operated at a single medical center during a 26-year period. Data on the timing and location of adenoma recurrence were recorded and possible correlations with patients' gender, age, presence of desmoid tumor, duodenal adenomas, type of anastomosis and number of operation stages were analyzed. RESULTS: Thirty-five (59%) patients had at least one adenoma in either the cuff or the pouch, including 20 with isolated cuff adenomas, 4 with isolated pouch adenomas and 11 patients with adenomas in both the pouch and cuff. There was no significant correlation between gender, age at surgery, type of anastomosis, number of operative stages and the development of pouch or cuff adenomas. Desmoid tumor and pouch adenomas were significantly correlated with cuff adenomas formation. Duodenal adenomas were associated with pouch adenomas. There was some relationship between the development of cuff adenomas and the burden of colonic polyps, as well as the presence of duodenal adenomas. CONCLUSION: Adenomas in both the pouch and cuff commonly occur following IPAA, mandating lifelong annual endoscopic surveillance. PMID- 26360377 TI - Broad-Band Activatable White-Opsin. AB - Currently, the use of optogenetic sensitization of retinal cells combined with activation/inhibition has the potential to be an alternative to retinal implants that would require electrodes inside every single neuron for high visual resolution. However, clinical translation of optogenetic activation for restoration of vision suffers from the drawback that the narrow spectral sensitivity of an opsin requires active stimulation by a blue laser or a light emitting diode with much higher intensities than ambient light. In order to allow an ambient light-based stimulation paradigm, we report the development of a 'white-opsin' that has broad spectral excitability in the visible spectrum. The cells sensitized with white-opsin showed excitability at an order of magnitude higher with white light compared to using only narrow-band light components. Further, cells sensitized with white-opsin produced a photocurrent that was five times higher than Channelrhodopsin-2 under similar photo-excitation conditions. The use of fast white-opsin may allow opsin-sensitized neurons in a degenerated retina to exhibit a higher sensitivity to ambient white light. This property, therefore, significantly lowers the activation threshold in contrast to conventional approaches that use intense narrow-band opsins and light to activate cellular stimulation. PMID- 26360379 TI - A p38 mitogen-activated protein kinase inhibitor attenuates cardiotonic steroids induced apoptotic and stress signaling in a Sw-71 cytotrophoblast cell line. AB - INTRODUCTION: Preeclampsia (preE) is characterized by abnormal placentation. Marinobufagenin (MBG), a cardiotonic steroid (CTS), inhibits the function of cytotrophoblast cells (CTBs). We demonstrated that CTSs induce anti-angiogenic and anti-proliferative effects in Sw-71 CTBs. This study tests that CTSs induce apoptotic and stress signaling. METHODS: Human extravillous Sw-71 CTBs were incubated with 0, 0.1, 1, 10, and 100 nM of each of three CTSs (MBG, cinobufatalin (CINO) and ouabain (OUB)) for 48 h. Some cells were pretreated with 10 MUM p38 mitogen-activated protein kinase (p38 MAPK) inhibitor (SB203580) for 2 h prior to CTSs treatment. We analyzed p38 MAPK phosphorylation, expression of pro-inflammatory protein cyclooxygenase-2 (Cox-2) and ratio of pro-apoptotic Bcl 2-associated X protein (Bax) to anti-apoptotic Bcl-2 protein by western blot in CTSs-treated CTBs lysates. Levels of vascular endothelial growth factor (VEGF), placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng) were measured in culture media using ELISA kits. Statistical comparisons were performed using analysis of variance with Duncan's post hoc test. RESULTS: p38 MAPK phosphorylation, expression of Cox-2 and Bax/Bcl 2 was upregulated (*p < 0.05) in CTBs exposed to >= 0.1 nM CTSs. Secretion of sFlt-1 and sEng were increased while VEGF and PIGF were decreased in Sw-71 CTBs treated >=1 nM of each CTSs (*p < 0.01 for each). The SB203580 pretreatment of CTBs significantly attenuated CTS-induced effects. DISCUSSION: Exposure of Sw-71 CTBs to CTSs induced apoptotic and stress signaling and causing anti-angiongenic effect. The observed diminution of CTS-induced signaling by SB203580 pretreatment implicates p38 MAPK as a regulator of these pathways. PMID- 26360378 TI - Childhood Symptoms of ADHD Overrule Comorbidity in Relation to Psychosocial Outcome at Age 15: A Longitudinal Study. AB - OBJECTIVE: Neurodevelopmental problems (NDPs) may influence the transition from childhood to adolescence. Our aim was to study long-term psychosocial outcomes of NDPs, focusing on ADHD. METHOD: Data was collected through a telephone interview with parents of twins at ages 9 or 12 years. NDP screen-positive children were clinically assessed at age 15; N = 450. Psychosocial outcome concerning peers, school, internalizing problems, antisocial behavior, alcohol misuse, drug misuse, and impaired daily functioning was examined. RESULTS: Even after controlling for other NDP comorbidity, screen-positivity for ADHD doubled or tripled the odds of later psychosocial problems. When controlling for parental education level, the significant effect of ADHD remained only for antisocial behavior and impaired daily functioning. CONCLUSIONS: Signs of NDPs as well as other psychiatric diagnoses at ages 9 or 12 years are associated with a more problematic adolescence. However, despite the presence of comorbidity, early ADHD symptoms stand out as the most important risk factor for later antisocial development and impaired daily functioning. PMID- 26360381 TI - Correction: The Prevalence of Anatomical Variations of the Median Nerve in the Carpal Tunnel: A Systematic Review and Meta-Analysis. PMID- 26360380 TI - Association of Psychosocial Conditions, Oral Health, and Dietary Variety with Intellectual Activity in Older Community-Dwelling Japanese Adults. AB - BACKGROUND: This study examined the factors related to intellectual activity in community-dwelling elderly persons. METHODS: Self-administered questionnaires mailed to all people aged >=65 years in a dormitory suburb in Japan (n = 15,210). The response rate was 72.2%. Analytical subjects (n = 8,910) were those who lived independently and completely answered questions about independent and dependent variables and covariates. Independent variables included psychosocial conditions (i.e., social activities, hobbies, and a sense that life is worth living (ikigai)), oral health (i.e., dental health behaviors and oral function evaluated by chewing difficulties, swallowing difficulties, and oral dryness), and dietary variety measured using the dietary variety score (DVS). A dependent variable was intellectual activity measured using the Tokyo Metropolitan Institute of Gerontology Index of Competence. Covariates included age, gender, family structure, pensions, body mass index, alcohol, smoking, medical history, self rated health, medications, cognitive function, depression, and falling. Logistic regression was used to estimate the odds ratio (OR) for poor intellectual activity. RESULTS: Poor intellectual activity was reported by 28.9% of the study population. After adjustment for covariates and independent variables, poor intellectual activity was significantly associated with nonparticipation in social activities (OR = 1.90, 95%CI = 1.61-2.24), having neither hobbies nor ikigai (3.13, 2.55-3.84), having neither regular dental visits nor daily brushing (1.70, 1.35-2.14), the poorest oral function (1.61, 1.31-1.98), and the lowest DVS quartile (1.96, 1.70-2.26). CONCLUSION: These results indicate that psychosocial conditions, oral health, and dietary variety are independently associated with intellectual activity in elderly persons. The factors identified in this study may be used in community health programs for maintaining the intellectual activity ability of the elderly. PMID- 26360383 TI - Quantum criticality in a uniaxial organic ferroelectric. AB - Tris-sarcosine calcium chloride (TSCC) is a highly uniaxial ferroelectric with a Curie temperature of approximately 130 K. By suppressing ferroelectricity with bromine substitution on the chlorine sites, pure single crystals were tuned through a ferroelectric quantum phase transition. The resulting quantum critical regime was investigated in detail and was found to persist up to temperatures of at least 30-40 K. The nature of long-range dipole interactions in uniaxial materials, which lead to non-analytical terms in the free-energy expansion in the polarization, predict a dielectric susceptibility varying as 1/T(3)close to the quantum critical point. Rather than this, we find that the dielectric susceptibility varies as 1/T(2) as expected and observed in better known multi axial systems. We explain this result by identifying the ultra-weak nature of the dipole moments in the TSCC family of crystals. Interestingly, we observe a shallow minimum in the inverse dielectric function at low temperatures close to the quantum critical point in paraelectric samples that may be attributed to the coupling of quantum polarization and strain fields. Finally, we present results of the heat capacity and electro-caloric effect and explain how the time dependence of the polarization in ferroelectrics and paraelectrics should be considered when making quantitative estimates of temperature changes induced by applied electric fields. PMID- 26360382 TI - Intraocular Pressure Changes in Non-Glaucomatous Patients Receiving Intravitreal Anti-Vascular Endothelial Growth Factor Agents. AB - PURPOSE: To study the prevalence of sustained intraocular pressure (IOP) elevation associated with intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents. METHODS: Prospective comparative study. Non glaucomatous patients scheduled to receive intravitreal injection of anti-VEGF therapy were recruited from an outpatient eye clinic, Songklanagarind Hospital between April 2013 and March 2014. The IOP was measured by Goldmann applanation tonometer before and at 1 hour, 1 week, 1 month, 3 months, and 6 months after injection. The IOP was compared using the repeated measures analysis. Sustained IOP elevation was defined as either an IOP > 21 mmHg or an increase from baseline >= 5 mmHg on two consecutive visits. RESULTS: Seventy eyes of 54 patients met the inclusion criteria. The most common diagnosis was diabetic macular edema (48%). The mean IOP +/- standard deviation (SD) before treatment was 13.7 +/- 2.8 mmHg. The means +/- SDs after treatment at 1 hour, 1 week, 1 month, 3 months, and 6 months were 11.3 +/- 2.6, 13.7 +/- 3.6, 14.1 +/- 3.3, 14.0 +/- 2.3, and 13.7 +/- 2.4 mmHg, respectively. A mean of IOP difference at 1 hour postinjection and at baseline was -2.36 +/- 2.5 mmHg (P < 0.001). Four of 70 treated eyes (5.7%) developed sustained IOP elevation (IOP >= 5 mmHg from baseline on two consecutive visits). The IOP returned to baseline levels after 1 month, in three eyes. One eye had sustained IOP elevation at 3 and 6 months follow-up. Thereafter, IOP returned to baseline level. There was no need of anti-glaucoma medication. CONCLUSIONS: After receiving intravitreal injection of anti-VEGF agent, a small proportion of non-glaucomatous eyes developed a sustained IOP elevation without requiring IOP-lowering treatment. At 1 hour postinjection, there was a significant reduction of the mean IOP compared with the baseline level. PMID- 26360384 TI - Psychiatry: the end of the timequake? PMID- 26360385 TI - Suicide prevention: a complex global challenge. PMID- 26360386 TI - Cognitive behaviour therapy for command hallucinations. PMID- 26360387 TI - Improving our understanding of youth suicide clusters. PMID- 26360388 TI - Violence, suicide, and all-cause mortality. PMID- 26360389 TI - Clozapine and patient safety. PMID- 26360390 TI - The early dementia prevention programme in Singapore. PMID- 26360391 TI - Mental health services: where do we go from here? PMID- 26360393 TI - New initiative aims to tackle shortfalls in mental health crisis care. PMID- 26360394 TI - Jane Pirkis: analysing and improving mental health in Australia. PMID- 26360395 TI - Goethe's Werther and its effects. PMID- 26360396 TI - A lot of nerve. PMID- 26360397 TI - Rise and fall. PMID- 26360398 TI - Out of time. PMID- 26360399 TI - Archives of pain. PMID- 26360400 TI - Cognitive behaviour therapy to prevent harmful compliance with command hallucinations (COMMAND): a randomised controlled trial. AB - BACKGROUND: Acting on command hallucinations in psychosis can have serious consequences for the individual and for other people and is a major cause of clinical and public concern. No evidence-based treatments are available to reduce this risk behaviour. We therefore tested our new cognitive therapy to challenge the perceived power of voices to inflict harm on the voice hearer if commands are not followed, thereby reducing the hearer's motivation to comply. METHODS: In COMMAND, a single-blind, randomised controlled trial, eligible participants from three centres in the UK who had command hallucinations for at least 6 months leading to major episodes of harm to themselves or other people were assigned in a 1: 1 ratio to cognitive therapy for command hallucinations + treatment as usual versus just treatment as usual for 9 months. Only the raters were masked to treatment assignment. The primary outcome was harmful compliance. Analysis was by intention to treat. The trial is registered, number ISRCTN62304114. FINDINGS: 98 (50%) of 197 participants were assigned to cognitive therapy for command hallucinations + treatment as usual and 99 (50%) to treatment as usual. At 18 months, 39 (46%) of 85 participants in the treatment as usual group fully complied with the voices compared with 22 (28%) of 79 in the cognitive therapy for command hallucinations + treatment as usual group (odds ratio 0.45, 95% CI 0.23-0.88, p=0.021). At 9 months the treatment effect was not significant (0.74, 0.40-1.39, p=0.353). However, the treatment by follow-up interaction was not significant and the treatment effect common to both follow-up points was 0.57 (0.33-0.98, p=0.042). INTERPRETATION: This is the first trial to show a clinically meaningful reduction in risk behaviour associated with commanding voices. We will next determine if change in power was the mediator of change. Further more complex trials are needed to identify the most influential components of the treatment in reducing power and compliance. FUNDING: UK Medical Research Council and the National Institute for Health Research. PMID- 26360401 TI - Newspaper coverage of suicide and initiation of suicide clusters in teenagers in the USA, 1988-96: a retrospective, population-based, case-control study. AB - BACKGROUND: Public health and clinical efforts to prevent suicide clusters are seriously hampered by the unanswered question of why such outbreaks occur. We aimed to establish whether an environmental factor-newspaper reports of suicide has a role in the emergence of suicide clusters. METHODS: In this retrospective, population-based, case-control study, we identified suicide clusters in young people aged 13-20 years in the USA from 1988 to 1996 (preceding the advent of social media) using the time-space Scan statistic. For each cluster community, we selected two matched non-cluster control communities in which suicides of similarly aged youth occurred, from non-contiguous counties within the same state as the cluster. We examined newspapers within each cluster community for stories about suicide published in the days between the first and second suicides in the cluster. In non-cluster communities, we examined a matched length of time after the matched control suicide. We used a content-analysis procedure to code the characteristics of each story and compared newspaper stories about suicide published in case and control communities with mixed-effect regression analyses. FINDINGS: We identified 53 suicide clusters, of which 48 were included in the media review. For one cluster we could identify only one appropriate control; therefore, 95 matched control communities were included. The mean number of news stories about suicidal individuals published after an index cluster suicide (7.42 [SD 10.02]) was significantly greater than the mean number of suicide stories published after a non-cluster suicide (5.14 [6.00]; p<0.0001). Several story characteristics, including front-page placement, headlines containing the word suicide or a description of the method used, and detailed descriptions of the suicidal individual and act, appeared more often in stories published after the index cluster suicides than after non-cluster suicides. INTERPRETATION: Our identification of an association between newspaper reports about suicide (including specific story characteristics) and the initiation of teenage suicide clusters should provide an empirical basis to support efforts by mental health professionals, community officials, and the media to work together to identify and prevent the onset of suicide clusters. FUNDING: US National Institute of Mental Health and American Foundation for Suicide Prevention. PMID- 26360402 TI - Monitoring white blood cell count in adult patients with schizophrenia who are taking clozapine: a cost-effectiveness analysis. AB - BACKGROUND: Long-term monitoring of white blood cell count is compulsory in patients taking clozapine, although the incidence of drug-induced agranulocytosis is lower than previously expected. The cost-effectiveness of this monitoring is unknown. We aimed to assess the cost-effectiveness of various strategies to monitor white blood cell count in adult patients with schizophrenia taking clozapine. METHODS: We assessed the cost-effectiveness of four strategies for monitoring white blood cell count (national strategies used in the UK, USA, and European countries, and a hypothetical 8-week strategy) compared with that of no monitoring. We used a semi-Markov model to do the cost-utility analysis from a health-care perspective with a 3-year time horizon, assuming a probability of 0.7% that a patient would develop agranulocytosis. Clinical and resource parameters were based on data from national registries of patients treated with clozapine, study cohorts, and a pharmacovigilance database; we derived estimates of health-related quality of life and mortality from the scientific literature. We assessed model uncertainty, including time horizon, with one-way and probabilistic sensitivity analyses. FINDINGS: Compared with no monitoring, all four monitoring strategies increased quality-adjusted survival by less than 1 day per patient; more than 5000 patients would need to be monitored to avoid one death. The incremental cost-effectiveness ratios (ICERs) were at least US$970 000 per quality-adjusted life-year gained for all four strategies compared with no monitoring. The ICERs were highest in the strategies with highest frequencies and longest durations of monitoring. The results remained robust in the one-way and probabilistic sensitivity analyses, suggesting that no monitoring had the highest probability of being cost effective. INTERPRETATION: Existing strategies for monitoring white blood cell count in patients taking clozapine, based on divergent national requirements, do not seem to be cost effective. This finding should be taken into account by public health authorities and policy makers in the revision of guidance for clozapine prescription. FUNDING: University Hospitals of Geneva. PMID- 26360403 TI - The neurobiology of suicide. AB - The stress-diathesis model posits that suicide is the result of an interaction between state-dependent (environmental) stressors and a trait-like diathesis or susceptibility to suicidal behaviour, independent of psychiatric disorders. Findings from post-mortem studies of the brain and from genomic and in-vivo neuroimaging studies indicate a biological basis for this diathesis, indicating the importance of neurobiological screening and interventions, in addition to cognitive and mood interventions, in the prevention of suicide. Early-life adversity and epigenetic mechanisms might explain some of the link between suicide risk and brain circuitry and neurochemistry abnormalities. Results from a range of studies using diverse designs and post-mortem and in-vivo techniques show impairments of the serotonin neurotransmitter system and the hypothalamic pituitary-adrenal axis stress-response system in the diathesis for suicidal behaviour. These impairments manifest as impaired cognitive control of mood, pessimism, reactive aggressive traits, impaired problem solving, over-reactivity to negative social signs, excessive emotional pain, and suicidal ideation, leading to suicidal behaviour. Biomarkers related to the diathesis might help to inform risk-assessment procedures and treatment choice in the prevention of suicide. PMID- 26360404 TI - The psychology of suicidal behaviour. AB - The causes of suicidal behaviour are not fully understood; however, this behaviour clearly results from the complex interaction of many factors. Although many risk factors have been identified, they mostly do not account for why people try to end their lives. In this Review, we describe key recent developments in theoretical, clinical, and empirical psychological science about the emergence of suicidal thoughts and behaviours, and emphasise the central importance of psychological factors. Personality and individual differences, cognitive factors, social aspects, and negative life events are key contributors to suicidal behaviour. Most people struggling with suicidal thoughts and behaviours do not receive treatment. Some evidence suggests that different forms of cognitive and behavioural therapies can reduce the risk of suicide reattempt, but hardly any evidence about factors that protect against suicide is available. The development of innovative psychological and psychosocial treatments needs urgent attention. PMID- 26360405 TI - Effects of suicide bereavement on mental health and suicide risk. AB - Between 48 million and 500 million people are thought to experience suicide bereavement every year. Over the past decade, increased policy attention has been directed towards suicide bereavement, but with little evidence to describe the effect of exposure or to provide appropriate responses. We used a systematic approach to carry out a narrative review of studies of the effect of suicide bereavement on mortality, mental health, and social functioning, and compared them with effects from other bereavements. We found 57 studies that satisfied strict inclusion criteria. Results from these studies suggested that exposure to suicide of a close contact is associated with several negative health and social outcomes, depending on an individual's relationship to the deceased. These effects included an increased risk of suicide in partners bereaved by suicide, increased risk of required admission to psychiatric care for parents bereaved by the suicide of an offspring, increased risk of suicide in mothers bereaved by an adult child's suicide, and increased risk of depression in offspring bereaved by the suicide of a parent. Some evidence was shown for increased rejection and shame in people bereaved by suicide across a range of kinship groups when data were compared with reports of relatives bereaved by other violent deaths. Policy recommendations for support services after suicide bereavement heavily rely on the voluntary sector with little input from psychiatric services to address described risks. Policymakers should consider how to strengthen health and social care resources for people who have been bereaved by suicide to prevent avoidable mortality and distress. PMID- 26360406 TI - Ticking the boxes. PMID- 26360407 TI - Bifunctional chelating agents based on ionic carbosilane dendrons with DO3A at the focal point and their complexation behavior with copper(II). AB - A synthetic protocol has been designed to incorporate the DO3A ligand to the focal point of cationic or anionic carbosilane dendrons, affording a set of bifunctional chelating agents (BFCAs) useful for potential biomedical applications. The complexation behavior study of ionic BFCAs has been accomplished by UV-vis and electron paramagnetic resonance spectroscopy as well as potentiometric titrations. The presence of the dendron branches modifies the complexation capacity of the macrocyclic ring with respect to that of the 1,4,7,10-tetraazacyclodocecane-N,N',N",N'''-tetraacetic acid (DOTA) ligand. Also, a different behavior has been observed in the carboxylate-terminated dendrons against analogous sulfonate- or amine-terminated dendrons in the contribution of the branches and peripheral groups to the coordination modes. The presence or not of Cu-S2O2 coordination sites and the generation can be important factors to take into account for considering a particular biomedical application. PMID- 26360408 TI - Organizational barriers associated with the implementation of national essential medicines policy: A cross-sectional study of township hospitals in China. AB - This study identifies potential organizational barriers associated with the implementation of the Chinese National Essential Medicines Policy (NEMP) in rural primary health care institutions. We used a multistage sampling strategy to select 90 township hospitals from six provinces, two from each of eastern, middle, and western China. Data relating to eight core NEMP indicators and institutional characteristics were collected from January to September 2011, using a questionnaire. Prescription-associated indicators were calculated from 9000 outpatient prescriptions selected at random. We categorized the eight NEMP indicators using an exploratory factor analysis, and performed linear regressions to determine the association between the factor scores and institution-level characteristics. The results identified three main factors. Overall, low levels of expenditure of medicines (F1) and poor performance in rational use of medicines (F2) were evident. The availability of medicines (F3) varied significantly across both hospitals and regions. Factor scores had no significant relationship with hospital size (in terms of number of beds and health workers); however, they were associated with revenue and structure of the hospital, patient service load, and support for health workers. Regression analyses showed that public finance per health worker was negatively associated with the availability of medicines (p < 0.05), remuneration of prescribers was positively associated with higher performance in the rational use of medicines (p < 0.05), and drug sales were negatively associated with higher levels of drug expenditure (p < 0.01). In conclusion, irrational use of medicines remains a serious issue, although the financial barriers for gaining access to essential medicines may be less for prescribers and consumers. Limited public finance from local governments may reduce medicine stock lines of township hospitals and lead them to seek alternative sources of income, jeopardizing their capacity to meet the needs of local consumers. PMID- 26360409 TI - A termination criterion for parameter estimation in stochastic models in systems biology. AB - Parameter estimation procedures are a central aspect of modeling approaches in systems biology. They are often computationally expensive, especially when the models take stochasticity into account. Typically parameter estimation involves the iterative optimization of an objective function that describes how well the model fits some measured data with a certain set of parameter values. In order to limit the computational expenses it is therefore important to apply an adequate stopping criterion for the optimization process, so that the optimization continues at least until a reasonable fit is obtained, but not much longer. In the case of stochastic modeling, at least some parameter estimation schemes involve an objective function that is itself a random variable. This means that plain convergence tests are not a priori suitable as stopping criteria. This article suggests a termination criterion suited to optimization problems in parameter estimation arising from stochastic models in systems biology. The termination criterion is developed for optimization algorithms that involve populations of parameter sets, such as particle swarm or evolutionary algorithms. It is based on comparing the variance of the objective function over the whole population of parameter sets with the variance of repeated evaluations of the objective function at the best parameter set. The performance is demonstrated for several different algorithms. To test the termination criterion we choose polynomial test functions as well as systems biology models such as an Immigration-Death model and a bistable genetic toggle switch. The genetic toggle switch is an especially challenging test case as it shows a stochastic switching between two steady states which is qualitatively different from the model behavior in a deterministic model. PMID- 26360411 TI - Timing of adjuvant chemotherapy and its relation to survival among patients with stage III colon cancer. AB - BACKGROUND: Currently available data suggest that delaying the start of adjuvant chemotherapy in colon cancer patients has a detrimental effect on survival. We analysed which factors impact on the timing of adjuvant chemotherapy and evaluated the influence on overall survival (OS). PATIENTS AND METHODS: Stage III colon cancer patients who underwent resection and received adjuvant chemotherapy between 2008 and 2013 were selected from the Netherlands Cancer Registry. Timing of adjuvant chemotherapy was subdivided into: ? 4, 5-6, 7-8, 9-10, 11-12 and 13 16 weeks post-surgery. Multivariable regressions were performed to assess the influence of several factors on the probability of starting treatment within 8 weeks post-surgery and to evaluate the association of timing of adjuvant chemotherapy with 5-year OS. RESULTS: 6620 patients received adjuvant chemotherapy, 14% commenced after 8 weeks. Factors associated with starting treatment after 8 weeks were older age (Odds ratio (OR) 65-74 versus < 65 years 1.3 (95% confidence interval (CI): 1.14-1.58); OR ? 75 versus < 65 years 1.6 (1.25-1.94)), emergency resection (OR 1.8 (1.41-2.32)), anastomotic leakage (OR 8.1 (6.14-10.62)), referral to another hospital for adjuvant chemotherapy (OR 1.9 (1.36-2.57)) and prolonged postoperative hospital admission (OR 4.7 (3.30-6.68)). Starting 5-8 weeks post-surgery showed no decrease in OS compared to initiation within 4 weeks (Hazard ratio (HR) 5-6 weeks 0.9 (0.79-1.11); HR 7-8 weeks 1.1 (0.91-1.30)). However, commencing beyond 8 weeks was associated with decreased OS compared to initiation within 8 weeks (HR 9-10 weeks 1.4 (1.21-1.68); HR 11-12 weeks 1.3 (1.06-1.59); HR 13-16 weeks 1.7 (1.23-2.23)). CONCLUSION: Our data support initiating adjuvant chemotherapy in stage III colon cancer patients within 8 weeks post-surgery. PMID- 26360412 TI - Sleep quality, but not quantity, is associated with self-perceived minor error rates among emergency department nurses. AB - INTRODUCTION: The emergency department (ED) is demanding and high risk. The impact of sleep quantity has been hypothesized to impact patient care. This study investigated the hypothesis that fatigue and impaired mentation, due to sleep disturbance and shortened overall sleeping hours, would lead to increased nursing errors. METHODS: This is a prospective observational study of 30 ED nurses using self-administered survey and sleep architecture measured by wrist actigraphy as predictors of self-reported error rates. An actigraphy device was worn prior to working a 12-hour shift and nurses completed the Pittsburgh Sleep Quality Index (PSQI). Error rates were reported on a visual analog scale at the end of a 12 hour shift. RESULTS: The PSQI responses indicated that 73.3% of subjects had poor sleep quality. Lower sleep quality measured by actigraphy (hours asleep/hours in bed) was associated with higher self-perceived minor errors. Sleep quantity (total hours slept) was not associated with minor, moderate, nor severe errors. DISCUSSION: Our study found that ED nurses' sleep quality, immediately prior to a working 12-hour shift, is more predictive of error than sleep quantity. These results present evidence that a "good night's sleep" prior to working a nursing shift in the ED is beneficial for reducing minor errors. PMID- 26360413 TI - The impact of HIRAID on emergency nurses' self-efficacy, anxiety and perceived control: A simulated study. AB - INTRODUCTION: Emergency nurses must perform accurate and complete comprehensive patient assessments to establish patient treatment needs and expedite care. AIM: To evaluate the impact of a structured approach to emergency nursing assessment following triage, on novice emergency nurses' anxiety, self-efficacy and perceptions of control. METHODS: Thirty eight early career emergency nurses from five Australian hospitals performed an initial patient assessment in an immersive clinical simulated scenario, before and after undertaking training in HIRAID, an evidence-informed patient assessment framework for emergency nurses. Immediately following each scenario the nurses completed a questionnaire scoring anxiety, self-efficacy and perceptions of control levels. Paired sample t-tests and effect sizes were calculated. RESULTS: Participant anxiety levels were lower after HIRAID training compared to before undertaking the training (Mean (SD) = 53.26 (10.76) vs 47.46 (9.96), P = 0.002). Self-efficacy levels in assessment performance increased (189.32 (66.48) vs 214.06 (51.35), P = 0.001). There was no change in perceptions of control (31.24 (7.38) vs 30.98 (8.38), P = 0.829). DISCUSSION: High levels of anxiety and low levels of self-efficacy are known to be negatively correlated with clinical reasoning skills and performance. CONCLUSION: The effect of HIRAID training on reducing anxiety and increasing self efficacy has the potential to improve emergency nurses' assessment performance and the quality and safety of patient care. PMID- 26360410 TI - The Protein Tyrosine Phosphatase Rptpzeta Suppresses Osteosarcoma Development in Trp53-Heterozygous Mice. AB - Osteosarcoma (OS), a highly aggressive primary bone tumor, belongs to the most common solid tumors in growing children. Since specific molecular targets for OS treatment remain to be identified, surgical resection combined with multimodal (neo-)adjuvant chemotherapy is still the only way to help respective individuals. We have previously identified the protein tyrosine phosphatase Rptpzeta as a marker of terminally differentiated osteoblasts, which negatively regulates their proliferation in vitro. Here we have addressed the question if Rptpzeta can function as a tumor suppressor protein inhibiting OS development in vivo. We therefore analyzed the skeletal phenotype of mice lacking Ptprz1, the gene encoding Rptpzeta on a tumor-prone genetic background, i.e. Trp53-heterozygosity. By screening a large number of 52 week old Trp53-heterozygous mice by contact radiography we found that Ptprz1-deficiency significantly enhanced OS development with 19% of the mice being affected. The tumors in Ptprz1-deficient Trp53 heterozygous mice were present in different locations (spine, long bones, ribs), and their OS nature was confirmed by undecalcified histology. Likewise, cell lines derived from the tumors were able to undergo osteogenic differentiation ex vivo. A comparison between Ptprz1-heterozygous and Ptprz1-deficient cultures further revealed that the latter ones displayed increased proliferation, a higher abundance of tyrosine-phosphorylated proteins and resistance towards the influence of the growth factor Midkine. Our findings underscore the relevance of Rptpzeta as an attenuator of proliferation in differentiated osteoblasts and raise the possibility that activating Rptpzeta-dependent signaling could specifically target osteoblastic tumor cells. PMID- 26360414 TI - Intrapartum electrocardiogram alteration in fetuses with congenital heart disease: a case-control study. AB - OBJECTIVE: To assess if the fetal electrocardiogram especially ST segment is modified by congenital heart diseases: modifications in frequencies of the different ST events and modifications in signal quality. STUDY DESIGN: A retrospective case-control study, comparing frequencies of the different ST events and the quality of the signal between fetuses with congenital heart diseases and fetuses without congenital heart disease. From 2000 to 2011, fifty eight fetuses with congenital heart disease had their heart rate recording using a STAN device during labor. Control group was fetuses who were born just before a case and had a STAN as a second line for intrapartum surveillance. Cases and controls were matched on parity, gestational age at birth, presence of growth restriction and umbilical artery pH. Frequencies of the different ST event and quality of the signal were first analyzed for the global labor recording, and then separately for the first and the second phase of labor. RESULTS: No statistically significant difference in ST event frequencies between fetuses with congenital heart disease and the control group was found. Regarding the quality of the signal, 11.49% (+/-18.82) of recording time is a signal loss for fetus with congenital heart disease whereas only 5.18% (+/-10.67) for the control group (p=0.028). CONCLUSION: This is the first study investigating for intrapartum electrocardiogram modification in fetus with congenital heart disease. Congenital heart diseases do not modify frequencies of ST events. PMID- 26360415 TI - Dengue rapid nanodiagnostic test: What to be concerned. PMID- 26360416 TI - Cost-effectiveness: A challenge for dengue rapid nanodiagnostic tests. PMID- 26360418 TI - Conceptualising quality of life outcomes for women participating in testing for sexually transmitted infections: A systematic review and meta-synthesis of qualitative research. AB - Many public health interventions have aims which are broader than health alone; this means that there are difficulties in using outcome measures that capture health effects only, such as Quality Adjusted Life Years (QALYs). Sexually Transmitted Infections (STIs) are a major public health concern both in the UK and globally, with Chlamydia trachomatis being the most common bacterial STI worldwide. There is scope for the wider use of qualitative syntheses in health related research; in this study we highlight their potential value in informing outcome identification, particularly for public health interventions where a broad range of outcomes may need to be considered. This article presents a systematic review and meta-ethnography of qualitative studies that investigated women's experiences of thinking about and participating in testing for chlamydia. The meta-ethnography highlights issues relating to beliefs about STIs and testing, assessing risk and interpreting symptoms, emotional responses to testing, coping with diagnosis, relationship with sex partners(s), informal support, and interaction with health care services. The study findings suggest that women can experience a range of impacts on their health and quality of life. It is important that this range of effects is taken into account within evaluations, to ensure that decision makers are fully informed about the outcomes associated with screening interventions, and ultimately, to make sure that appropriate interventions are available to support women in maintaining good sexual health. PMID- 26360419 TI - Unemployment transitions and self-rated health in Europe: A longitudinal analysis of EU-SILC from 2008 to 2011. AB - The Great Recession of 2008 has led to elevated unemployment in Europe and thereby revitalised the question of causal health effects of unemployment. This article applies fixed effects regression models to longitudinal panel data drawn from the European Union Statistics on Income and Living Conditions for 28 European countries from 2008 to 2011, in order to investigate changes in self rated health around the event of becoming unemployed. The results show that the correlation between unemployment and health is partly due to a decrease in self rated health as people enter unemployment. Such health changes vary by country of domicile, and by individual age; older workers have a steeper decline than younger workers. Health changes after the unemployment spell reveal no indication of adverse health effects of unemployment duration. Overall, this study indicates some adverse health effects of unemployment in Europe--predominantly among older workers. PMID- 26360417 TI - CRISPR/Cas9 System as an Agent for Eliminating Polyomavirus JC Infection. AB - Progressive multifocal leukoencephalopathy (PML) is a fatal demyelinating disease of the central nervous system (CNS) caused by reactivation of the human polyomavirus JCV gene expression and its replication in oligodendrocytes, the myelin producing cells in the brain. Once a rare disease seen in patients with lymphotproliferative and myeloproliferative disorders, PML has been seen more frequently in HIV-1 positive/AIDS patients as well as patients undergoing immunomodulatory therapy due for autoimmune disorders including multiple sclerosis, rheumatoid arthritis, and others. As of now there is no cure for PML and in most cases disease progression leads to death within two years. Similar to other polyomaviruses, the JCV genome is small circular double stranded DNA that includes coding sequences for the viral early protein, T-antigen, which is critical for directing viral reactivation and lytic infection. Here, we employ a newly developed gene editing strategy, CRISPR/Cas9, to introduce mutations in the viral genome and, by inactivating the gene encoding T-antigen, inhibit viral replication. We first used bioinformatics screening and identified several potential targets within the JCV T-antigen gene that can serve as sites for the creation of guide RNAs (gRNAs) for positioning the Cas9 nuclease on the designated area of the viral genome for editing. Results from a series of integrated genetic and functional studies showed that transient or conditional expression of Cas9 and gRNAs specifically targets the DNA sequences corresponding to the N-terminal region of T-antigen, and by introducing mutation, interferes with expression and function of of the viral protein, hence suppressing viral replication in permissive cells. Results from SURVEYOR assay revealed no off target effects of the JCV-specific CRISPR/Cas9 editing apparatus. These observations provide the first evidence for the employment of a gene editing strategy as a promising tool for the elimination of the JCV genome and a potential cure for PML. PMID- 26360420 TI - Beyond Critical Congenital Heart Disease: Newborn Screening Using Pulse Oximetry for Neonatal Sepsis and Respiratory Diseases in a Middle-Income Country. AB - BACKGROUND: Studies on pulse oximetry screening for neonatal sepsis and respiratory disease in a middle-income country are lacking. Newborn screening for critical congenital heart disease (CCHD) using pulse oximetry is an effective and life-saving strategy in developed countries. While most studies have reported false-positive results during CCHD screening, they have not elaborated on the detected disease types. We studied the effectiveness and outcomes of pulse oximetry newborn screening for non-cardiac hypoxemic diseases such as neonatal sepsis, respiratory diseases, and CCHD in a middle-income country. METHODS AND FINDINGS: In a pilot study performed at the University Malaya Medical Centre (UMMC), Malaysia, all apparently healthy term newborns, delivered at UMMC were screened pre-discharge using pulse oximetry. Echocardiography was performed for newborns that had positive screening results on two separate occasions, 1-h apart. Newborns with normal echocardiograms were evaluated and treated for other non-cardiac diseases. Fifteen of 5247 term newborns had positive screening results. The median age at screening was 20 h. Thirteen newborns (0.24%) had significant non-cardiac diseases: sepsis (n = 2) and respiratory diseases (n = 11) that required hospitalization and treatment. The remaining two newborns with normal antenatal ultrasonograms had positive screening test and confirmed to have CCHD. Another 18 newborns with negative screening test were later admitted for treatment of sepsis (n = 16) and penumonia (n = 2). All newborns were treated and alive at the end of the study. The sensitivity and specificity of pulse oximetry screening for non-cardiac diseases were 42% and 99.9% respectively, and 100% and 99.7% for CCHD, respectively. CONCLUSIONS: Routine pulse oximetry screening test was effective in identifying newborns with CCHD and other hypoxemia illnesses, which may led to potential life-threatening condition. This study showed that the expanded use of pulse oximetry has immediate implications for low- and middle income countries contemplating strategies to reduce neonatal mortality and morbidity. ABBREVIATIONS: ASD, atrial septal defect; CCHD, critical congenital heart disease; CRP, C-reactive protein; CXR, chest radiographs; NDI, neurodevelopment impairment; PPHN, persistent pulmonary hypertension of the newborn; PDA, patent ductus arteriosus; PFO, patent foramen ovale; TGA, transposition of great artery; TTN, transient tachypnoea of the newborn; VSD, ventricular septal defect. PMID- 26360421 TI - Recommendations for the treatment of Sjogren's syndrome. AB - The recommendations proposed by the Sjogren's Syndrome Committee of the Brazilian Society of Rheumatology for the treatment of Sjogren's syndrome were based on a systematic review of literature in Medline (PubMed) and the Cochrane databases until October 2014 and on expert opinion in the absence of studies on the subject. 131 items classified according to Oxford & Grade were included. These recommendations were developed in order to guide the appropriate management and facilitate the access to treatment for those patients with an appropriate indication, considering the Brazilian socioeconomic context and pharmacological agents available in this country. PMID- 26360422 TI - Surgical Clipping versus Endovascular Intervention for the Treatment of Subarachnoid Hemorrhage Patients in New York State. AB - OBJECT: Randomized trials have demonstrated a survival benefit for endovascular treatment of ruptured cerebral aneurysms. We investigated the association of surgical clipping and endovascular coiling with outcomes in subarachnoid hemorrhage (SAH) patients in a real-world regional cohort. METHODS: We performed a cohort study involving patients with ruptured cerebral aneurysms, who underwent surgical clipping, or endovascular coiling from 2009-2013 and were registered in the Statewide Planning and Research Cooperative System (SPARCS) database. An instrumental variable analysis was used to investigate the association of treatment technique with outcomes. RESULTS: Of the 4,098 patients undergoing treatment, 2,585 (63.1%) underwent coiling, and 1,513 (36.9%) underwent clipping. Using an instrumental variable analysis, we did not identify a difference in inpatient mortality [marginal effect (ME), -0.56; 95% CI, -1.03 to 0.02], length of stay (LOS) (ME, 1.72; 95% CI, -3.39 to 6.84), or the rate of 30-day readmissions (ME, -0.30; 95% CI, -0.82 to 0.22) between the two treatment techniques for patients with SAH. Clipping was associated with a higher rate of discharge to rehabilitation (ME, 0.63; 95% CI, 0.24 to 1.01). In sensitivity analysis, mixed effect regression, and propensity score adjusted regression models demonstrated identical results. CONCLUSIONS: Using a comprehensive all payer cohort of patients in New York State presenting with aneurysmal SAH we did not identify an association of treatment method with mortality, LOS or 30-day readmission. Clipping was associated with a higher rate of discharge to rehabilitation. PMID- 26360423 TI - A versatile approach towards multivalent saccharide displays on magnetic nanoparticles and phospholipid vesicles. AB - A simple synthetic route has been devised for the production of coating agents that can give multivalent displays of saccharides on the surface of magnetite nanoparticles and phospholipid vesicles. A versatile and potentially high throughput condensation reaction allowed the rapid synthesis of a variety of glycosylhydrazide conjugates with lipid, resorcinol or catechol termini, each in good yield and high anomeric purity. The hydrolytic stability of these adducts was assessed in D2O at different pD values using (1)H-NMR spectroscopy, whilst quartz crystal microbalance with dissipation monitoring (QCM-D) confirmed that the saccharide functionality on bilayers and on nanoparticles was still available to lectins. These multivalent saccharide displays promoted nanoparticle interactions with cells, for example N-acetylglucosamine-coated nanoparticles interacted much more effectively with 3T3 fibroblasts than uncoated nanoparticles with these cells. Despite potential sensitivity to oxidation, catechol coatings on magnetite nanoparticles were found to be more stable and generate better nanoparticle interactions with fibroblasts than resorcinol coatings. PMID- 26360424 TI - This year's model. PMID- 26360425 TI - Supporting recovery from psychosis: assessment of REFOCUS. PMID- 26360426 TI - Depression and anxiety: their insidious dance. PMID- 26360427 TI - A holistic approach to child maltreatment. PMID- 26360428 TI - Grave news about adolescents who engage in self-poisoning. PMID- 26360429 TI - Staging and psychosocial early intervention in bipolar disorder. PMID- 26360430 TI - Tobacco harm reduction in people with serious mental illnesses. PMID- 26360431 TI - The mental health of HIV-positive adolescents. PMID- 26360432 TI - Corrections. PMID- 26360433 TI - Global mental health and neuroscience: different synergies might be needed. PMID- 26360434 TI - Education and global mental health. PMID- 26360435 TI - Global mental health and neuroscience: different synergies might be needed - Authors' reply. PMID- 26360436 TI - Depression and violence-what do we really know? PMID- 26360437 TI - Depression and violence-what do we really know? - Authors' reply. PMID- 26360439 TI - Under the Maytree. PMID- 26360440 TI - Kendrick Lamar, street poet of mental health. PMID- 26360441 TI - Helen Herrman: president elect of the World Psychiatric Association. PMID- 26360446 TI - Supporting recovery in patients with psychosis through care by community-based adult mental health teams (REFOCUS): a multisite, cluster, randomised, controlled trial. AB - BACKGROUND: Mental health policy in many countries is oriented around recovery, but the evidence base for service-level recovery-promotion interventions is lacking. METHODS: We did a cluster, randomised, controlled trial in two National Health Service Trusts in England. REFOCUS is a 1-year team-level intervention targeting staff behaviour to increase focus on values, preferences, strengths, and goals of patients with psychosis, and staff-patient relationships, through coaching and partnership. Between April, 2011, and May, 2012, community-based adult mental health teams were randomly allocated to provide usual treatment plus REFOCUS or usual treatment alone (control). Baseline and 1-year follow-up outcomes were assessed in randomly selected patients. The primary outcome was recovery and was assessed with the Questionnaire about Processes of Recovery (QPR). We also calculated overall service costs. We used multiple imputation to estimate missing data, and the imputation model captured clustering at the team level. Analysis was by intention to treat. This trial is registered, number ISRCTN02507940. FINDINGS: 14 teams were included in the REFOCUS group and 13 in the control group. Outcomes were assessed in 403 patients (88% of the target sample) at baseline and in 297 at 1 year. Mean QPR total scores did not differ between the two groups (REFOCUS group 40.6 [SD 10.1] vs control 40.0 [10.2], adjusted difference 0.68, 95% CI -1.7 to 3.1, p=0.58). High team participation was associated with higher staff-rated scores for recovery-promotion behaviour change (adjusted difference -0.4, 95% CI -0.7 to -0.2, p=0.001) and patient-rated QPR interpersonal scores (-1.6, -2.7 to -0.5, p=0.005) at follow-up than low participation. Patients treated in the REFOCUS group incurred L1062 (95% CI -1103 to 3017) lower adjusted costs than those in the control group. INTERPRETATION: Although the primary endpoint was negative, supporting recovery might, from the staff perspective, improve functioning and reduce needs. Implementation of REFOCUS could increase staff recovery-promotion behaviours and improve patient rated recovery. FUNDING: National Institute for Health Research. PMID- 26360448 TI - Adult mental health consequences of peer bullying and maltreatment in childhood: two cohorts in two countries. AB - BACKGROUND: The adult mental health consequences of childhood maltreatment are well documented. Maltreatment by peers (ie, bullying) has also been shown to have long-term adverse effects. We aimed to determine whether these effects are just due to being exposed to both maltreatment and bullying or whether bullying has a unique effect. METHODS: We used data from the Avon Longitudinal Study of Parents and Children in the UK (ALSPAC) and the Great Smoky Mountains Study in the USA (GSMS) longitudinal studies. In ALSPAC, maltreatment was assessed as physical, emotional, or sexual abuse, or severe maladaptive parenting (or both) between ages 8 weeks and 8.6 years, as reported by the mother in questionnaires, and being bullied was assessed with child reports at 8, 10, and 13 years using the previously validated Bullying and Friendship Interview Schedule. In GSMS, both maltreatment and bullying were repeatedly assessed with annual parent and child interviews between ages 9 and 16 years. To identify the association between maltreatment, being bullied, and mental health problems, binary logistic regression analyses were run. The primary outcome variable was overall mental health problem (any anxiety, depression, or self-harm or suicidality). FINDINGS: 4026 children from the ALSPAC cohort and 1420 children from the GSMS cohort provided information about bullying victimisation, maltreatment, and overall mental health problems. The ALSPAC study started in 1991 and the GSMS cohort enrolled participants from 1993. Compared with children who were not maltreated or bullied, children who were only maltreated were at increased risk for depression in young adulthood in models adjusted for sex and family hardships according to the GSMS cohort (odds ratio [OR] 4.1, 95% CI 1.5-11.7). According to the ALSPAC cohort, those who were only being maltreated were not at increased risk for any mental health problem compared with children who were not maltreated or bullied. By contrast, those who were both maltreated and bullied were at increased risk for overall mental health problems, anxiety, and depression according to both cohorts and self-harm according to the ALSPAC cohort compared with neutral children. Children who were bullied by peers only were more likely than children who were maltreated only to have mental health problems in both cohorts (ALSPAC OR 1.6, 95% CI 1.1-2.2; p=0.005; GSMS 3.8, 1.8-7.9, p<0.0001), with differences in anxiety (GSMS OR 4.9; 95% CI 2.0-12.0), depression (ALSPAC 1.7, 1.1-2.7), and self-harm (ALSPAC 1.7, 1.1-2.6) between the two cohorts. INTERPRETATION: Being bullied by peers in childhood had generally worse long-term adverse effects on young adults' mental health. These effects were not explained by poly-victimisation. The findings have important implications for public health planning and service development for dealing with peer bullying. FUNDING: Wellcome Trust, Medical Research Council, Economic and Social Research Council, National Institute of Mental Health, the National Institute on Drug Abuse, NARSAD (Early Career Award), and the William T Grant Foundation. PMID- 26360447 TI - Secondary depression in severe anxiety disorders: a population-based cohort study in Denmark. AB - BACKGROUND: Depression and anxiety disorders are highly comorbid conditions and a worldwide disease burden; however, large-scale studies delineating their association are scarce. In this retrospective study, we aimed to assess the effect of severe anxiety disorders on the risk and course of depression. METHODS: We did a population-based cohort study with prospectively gathered data in Denmark using data from three Danish population registers: The Danish Civil Registration System, the Danish Psychiatric Central Register, and the Danish National Hospital Registry. We selected the cohort from people born in Denmark between Jan 1, 1955, and Dec 31, 2002, who we followed up from Jan 1, 1994, to Dec 31, 2012. The cohort was restricted to individuals with known parents. First, we investigated the effect of specific anxiety diagnoses on risk of single depressive episodes and recurrent depressive disorder. Second, we investigated the effect of comorbid anxiety on risk of readmission for depression, adjusting for sex, age, calendar year, parental age, place at residence at time of birth, and the interaction of age with sex. FINDINGS: We included 3,380,059 individuals in our study cohort. The adjusted incidence rate ratio (IRR) for single depressive episodes was 3.0 (95% CI 2.8-3.1, p<0.0001) and for recurrent depressive disorder was 5.0 (4.8-5.2) in patients with severe anxiety disorders compared with the general population. Compared with control individuals, the offspring of parents with anxiety disorders were more likely to be diagnosed with single depressive episodes (1.9, 1.8-2.0) or recurrent depressive disorder (2.1, 1.9-2.2). Comorbid anxiety increased the readmission rates in both patients with single depressive episodes and patients with recurrent depressive disorder. INTERPRETATION: Severe anxiety constitutes a significant risk factor for depression. Focusing on specific anxiety disorders might help to identify individuals at risk of depression, thereby providing new insights for prevention and treatment. FUNDING: The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH). PMID- 26360449 TI - Long-term outcomes following self-poisoning in adolescents: a population-based cohort study. AB - BACKGROUND: Suicide is the third most common cause of death among adolescents worldwide, and poisoning is the leading method of attempted suicide. Unlike more violent methods, survival after self-poisoning is common, providing an opportunity for secondary prevention. We determined the risk and time course of completed suicide after adolescent self-poisoning, and explored potential risk factors. METHODS: We did a population-based cohort study using multiple linked health-care databases in Ontario, Canada, from Jan 1, 2001, to Dec 31, 2012. We identified all adolescents aged 10-19 years presenting to hospital after a first self-poisoning episode. Each was matched with 50 population-based reference individuals with no such history, matching on age, sex, and year of cohort entry. The primary outcome was the risk of suicide after a first self-poisoning episode. Secondary analyses explored factors associated with suicide and self-poisoning repetition. FINDINGS: We identified 20,471 adolescents discharged from hospital after a first self-poisoning episode and 1,023,487 matched reference individuals. Over a median follow-up of 7.2 years (IQR 4.2-9.7), 248 (1%) adolescents discharged after self-poisoning died, 126 (51%) of whom died by suicide. The risk of suicide at 1 year after self-poisoning was greatly increased relative to reference individuals (hazard ratio [HR] 32.1, 95% CI 23.6-43.6), corresponding to a suicide rate of 89.6 (95% CI 75.2-106.7) per 100,000 person-years over the course of follow-up. The median time from hospital discharge to suicide was 3.0 years (IQR 1.1-5.3). Factors associated with suicide included recurrent self poisoning (adjusted HR 3.5, 95% CI 2.4-5.0), male sex (2.5, 1.8-3.6) and psychiatric care in the preceding year (1.7, 1.1-2.5). Adolescents admitted to hospital for self-poisoning were also more likely to die from accidents (5.2, 4.1 6.6) and from all causes (3.9, 2.8-5.4) during follow-up. INTERPRETATION: Self poisoning in adolescence is a strong predictor of suicide and premature death in the ensuing decade, and identifies a high-risk group for targeted secondary prevention. Suicide risk is increased for many years after the index hospital admission, emphasising the importance of sustained prevention efforts. FUNDING: The Canadian Drug Safety and Effectiveness Research Network, Ontario Ministry of Health and Long-Term Care, Paediatric Consultants Partnership. PMID- 26360450 TI - The management of adult psychiatric emergencies in low-income and middle-income countries: a systematic review. AB - The aim of this Review is to identify effective interventions and treatment guidelines to manage common types of psychiatric emergencies in non-specialist settings in low-income and middle-income countries. Mental health specialist services in low-income and middle-income countries are scarce. We did a systematic review of interventions for psychiatric emergencies and a literature search for low-income and middle-income-specific treatment guidelines for psychiatric emergencies. A dearth of high-quality guidelines and contextualised primary evidence for management of psychiatric emergencies in low-income and middle-income countries exists. Filling these gaps in present guidelines needs to be an urgent research priority in view of the adverse health and social consequences of such presentations and the present drive to scale up mental health care. PMID- 26360452 TI - Staging bipolar disorder: what data and what models are needed? AB - Although bipolar disorder is increasingly recognised as a spectrum of multisystem disorders (ie, bipolar disorders), proposed staging models and theories of bipolar disease progression often fail to incorporate longitudinal data or data from multiple domains of dysfunction. We propose that bipolar disorders are best thought of as syndromes, with different trajectories of development and progression for various symptoms and demographic groups. This inherent complexity might be better suited to non-traditional modelling techniques, potentially derived from chaos theory. In this Personal View, we propose an allostatic load framework to account for biomarkers of physiological symptom progression. We then suggest integration of two potential domains of biobehavioural markers: sleep and wake and circadian rhythm regulation and the behavioural activation system. A satisfactory model should account for the effects of developmental stage as well as demographic characteristics, including but not limited to sex, culture, ethnicity, and socioeconomic status. The ultimate goal of a staging model has to be to inform the development of targeted, stage-appropriate interventions to reduce the substantial burden of bipolar disorders on individuals and societies. PMID- 26360454 TI - Illicit psychotropic substances in the air: The state-of-art. AB - The occurrence of psychotropic substances (PSs) in the air is known since long time. Recently, attention was paid to illicit PS, with most investigations undertaken in Italy and Spain. In general, collection of illicit substances was performed through aspirating airborne particulates onto filters; afterwards, gas chromatography or high-performance liquid chromatography coupled with mass spectrometry were applied for the PS evaluation. Over twenty substances could be characterized simultaneously. Cocaine concentrations up to 17ngm(-3) were observed in Latin America, while this substance was absent (<0.003ngm(-3)) in Algiers (Algeria) and Pancevo (Serbia). Cannabinoids (comprising the psycho active principle Delta(9)-tetrahydrocannabinol [THC]) were high in the winter and very low in the summer (up to 6ngm(-3) and <0.1ngm(-3), respectively). Many other substances (e.g., heroin, ephedrine and drug by-products) occurred less frequently and at lesser extents (<20pgm(-3)). In Rome (Italy), investigations were carried out in interiors of dwellings, schools, an office and a coffee bar, all sites resulting affected by drugs. Besides, solid phase microextraction methods were applied to detect ketamine and methamphetamine in interiors. The PS concentrations depended on substance, physical-chemical contour, and internal or external type of locations. Air monitoring allows detecting the drug consumption or preparation, because illicit substances prevail in sites frequented by abusers. PMID- 26360451 TI - An evidence map of psychosocial interventions for the earliest stages of bipolar disorder. AB - Depression, schizophrenia, and bipolar disorder are three of the four most burdensome problems in people aged under 25 years. In psychosis and depression, psychological interventions are effective, low-risk, and high-benefit approaches for patients at high risk of first-episode or early-onset disorders. We review the use of psychological interventions for early-stage bipolar disorder in patients aged 15-25 years. Because previous systematic reviews had struggled to identify information about this emerging sphere of research, we used evidence mapping to help us identify the extent, distribution, and methodological quality of evidence because the gold standard approaches were only slightly informative or appropriate. This strategy identified 29 studies in three target groups: ten studies in populations at high risk for bipolar disorder, five studies in patients with a first episode, and 14 studies in patients with early-onset bipolar disorder. Of the 20 completed studies, eight studies were randomised trials, but only two had sample sizes of more than 100 individuals. The main interventions used were family, cognitive behavioural, and interpersonal therapies. Only behavioural family therapies were tested across all of our three target groups. Although the available interventions were well adapted to the level of maturity and social environment of young people, few interventions target specific developmental psychological or physiological processes (eg, ruminative response style or delayed sleep phase), or offer detailed strategies for the management of substance use or physical health. PMID- 26360455 TI - Enhanced removal of petroleum hydrocarbons using a bioelectrochemical remediation system with pre-cultured anodes. AB - Bioelectrochemical remediation (BER) systems such as microbial fuel cells (MFCs) have recently emerged as a green technology for the effective remediation of petroleum hydrocarbon contaminants (PH) coupled with simultaneous energy recovery. Recent research has shown that biofilms previously enriched for substrate degrading bacteria resulted in excellent performance in terms of substrate removal and electricity generation but the effects on hydrocarbon contaminant degradation were not examined. Here we investigate the differences between enriched biofilm anodes and freshly inoculated new anodes in diesel fed single chamber mediatorless microbial fuel cells (DMFC) using various techniques for the enhancement of PH contaminant remediation with concomitant electricity generation. An anodophilic microbial consortium previously selected for over a year through continuous culturing with a diesel concentration of about 800mgl(-1) and which now showed complete removal of this concentration of diesel within 30days was compared to that of a freshly inoculated new anode MFC (showing 83.4% removal of diesel) with a simultaneous power generation of 90.81mW/m(2) and 15.04mW/m(2) respectively. The behaviour of pre-cultured anodes at a higher concentration of PH (8000mgl(-1)) was also investigated. Scanning electron microscopy observation revealed a thick biofilm covering the pre-cultured anodic electrode but not the anode from the freshly inoculated MFC. High resolution imaging showed the presence of thin 60nm diametre pilus-like projections emanating from the cells. Anodic microbial community profiling confirmed that the selection for diesel degrading exoelectrogenic bacteria had occurred. Identification of a biodegradative gene (alkB) provided strong evidence of the catabolic pathway used for diesel degradation in the DMFCs. PMID- 26360456 TI - Perfluoroalkyl substances assessment in drinking waters from Brazil, France and Spain. AB - Human exposure to perfluoroalkyl substances (PFASs) occurs primarily via dietary intake and drinking water. In this study, 16 PFASs have been assessed in 96 drinking waters (38 bottled waters and 58 samples of tap water) from Brazil, France and Spain. The total daily intake and the risk index (RI) of 16 PFASs through drinking water in Brazil, France and Spain have been estimated. This study was carried out using an analytical method based on an online sample enrichment followed by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). The quality parameters of the analytical method were satisfactory for the analysis of the 16 selected compounds in drinking waters. Notably, the method limits of detection (MLOD) and method limits of quantification (MLOQ) were in the range of 0.15 to 8.76ng/l and 0.47 to 26.54ng/l, respectively. The results showed that the highest PFASs concentrations were found in tap water samples and the more frequently found compound was perfluorooctanesulfonic acid (PFOS), with mean concentrations of 7.73, 15.33 and 15.83ng/l in French, Spanish and Brazilian samples, respectively. In addition, PFOS was detected in all tap water samples from Brazil. The highest level of PFASs contamination in a single sample was 140.48ng/l in a sample of Spanish tap water. In turn, in bottled waters the highest levels were detected in a French sample with 116ng/l as the sum of PFASs. Furthermore, the most frequent compounds and those at higher concentrations were perfluoroheptanoic acid (PFHpA) with a mean of frequencies in the three countries of 51.3%, followed by perfluorobutanesulfonic acid (PFBS) (27.2%) and perfluorooctanoic acid (PFOA) (23.0%). Considering that bottled water is approximately 38% of the total intake, the total PFASs exposure through drinking water intake for an adult man was estimated to be 54.8, 58.0 and 75.6ng/person per day in Spain, France and Brazil, respectively. However, assuming that the water content in other beverages has at least the same levels of contamination as in bottled drinking water, these amounts were increased to 72.2, 91.4 and 121.0ng/person per day for an adult man in Spain, France and Brazil, respectively. The results of total daily intake in different gender/age groups showed that children are the most exposed population group through hydration with maximum values in Brazil of 2.35 and 2.01ng/kg body weight (BW)/day for male and female, respectively. Finally, the RI was calculated. In spite of the highest values being found in Brazil, it was demonstrated that, in none of the investigated countries, drinking water pose imminent risk associated with PFASs contamination. PMID- 26360457 TI - Dynamic integration of land use changes in a hydrologic assessment of a rapidly developing Indian catchment. AB - Rapid land use and land-cover changes strongly affect water resources. Particularly in regions that experience seasonal water scarcity, land use scenario assessments provide a valuable basis for the evaluation of possible future water shortages. The objective of this study is to dynamically integrate land use model projections with a hydrologic model to analyze potential future impacts of land use change on the water resources of a rapidly developing catchment upstream of Pune, India. For the first time projections from the urban growth and land use change model SLEUTH are employed as a dynamic input to the hydrologic model SWAT. By this means, impacts of land use changes on the water balance components are assessed for the near future (2009-2028) employing four different climate conditions (baseline, IPCC A1B, dry, wet). The land use change modeling results in an increase of urban area by +23.1% at the fringes of Pune and by +12.2% in the upper catchment, whereas agricultural land (-14.0% and 0.3%, respectively) and semi-natural area (-9.1% and -11.9%, respectively) decrease between 2009 and 2028. Under baseline climate conditions, these land use changes induce seasonal changes in the water balance components. Water yield particularly increases at the onset of monsoon (up to +11.0mm per month) due to increased impervious area, whereas evapotranspiration decreases in the dry season (up to -15.1mm per month) as a result of the loss of irrigated agricultural area. As the projections are made for the near future (2009-2028) land use change impacts are similar under IPCC A1B climate conditions. Only if more extreme dry years occur, an exacerbation of the land use change impacts can be expected. Particularly in rapidly changing environments an implementation of both dynamic land use change and climate change seems favorable to assess seasonal and gradual changes in the water balance. PMID- 26360458 TI - Analysis of trihalomethane precursor removal from sub-tropical reservoir waters by a magnetic ion exchange resin using a combined method of chloride concentration variation and surrogate organic molecules. AB - In small reservoirs in tropical islands in Japan, the disinfection by-product formation potential is high due to elevated concentrations of dissolved organic matter (DOM) and bromide. We employed a combined method of variation of chloride concentrations and the use of DOM surrogates to investigate removal mechanisms of bromide and different fractions of DOM by chloride-based magnetic ion exchange (MIEX(r)) resin. The DOM in reservoir waters was fractionated by resins based on their hydrophobicity, and characterized by size-exclusion chromatography and fluorescence excitation-emission matrix spectrophotometry. The hydrophobic acid (HPO acid) fraction was found to be the largest contributor of the trihalomethane (THM) precursors, while hydrophilic acid (HPI acid) was the most reactive precursors of all the four THM species. Bromide and DOM with a molecular weight (MW) greater than 1kDa, representing HPO acid (MW 1-3kDa) and HPI acid (MW 1 2kDa), were effectively removed by MIEX(r) resin; however, DOM with a MW lower than 1kDa, representing HPI non-acid, was only moderately removed. The removal of THM precursors by MIEX(r) resin was interfered by high chloride concentrations, which was similar to the removal of glutamic acid (HPI acid surrogate) and bromide. However, elevated chloride concentrations had only a minor effect on tannic acid (HPO acid surrogate) removal, indicating that HPO acid fraction was removed by a combination of ion exchange and physical adsorption on MIEX(r) resin. Our study demonstrated that the combined use of DOM surrogates and elevated chloride concentrations is an effective method to estimate the removal mechanisms of various DOM fractions by MIEX(r) resin. PMID- 26360459 TI - Uptake of uranium by aquatic plants growing in fresh water ecosystem around uranium mill tailings pond at Jaduguda, India. AB - Concentration of uranium was determined in aquatic plants and substrate (sediment or water) of fresh water ecosystem on and around uranium mill tailings pond at Jaduguda, India. Aquatic plant/substrate concentration ratios (CRs) of uranium were estimated for different sites on and around the uranium mill tailings disposal area. These sites include upstream and downstream side of surface water sources carrying the treated tailings effluent, a small pond inside tailings disposal area and residual water of this area. Three types of plant groups were investigated namely algae (filamentous and non-filamentous), other free floating & water submerged and sediment rooted plants. Wide variability in concentration ratio was observed for different groups of plants studied. The filamentous algae uranium concentration was significantly correlated with that of water (r=0.86, p<0.003). For sediment rooted plants significant correlation was found between uranium concentration in plant and the substrate (r=0.88, p<0.001). Both for other free floating species and sediment rooted plants, uranium concentration was significantly correlated with Mn, Fe, and Ni concentration of plants (p<0.01). Filamentous algae, Jussiaea and Pistia owing to their high bioproductivity, biomass, uranium accumulation and concentration ratio can be useful for prospecting phytoremediation of stream carrying treated or untreated uranium mill tailings effluent. PMID- 26360460 TI - Aggregation of TiO2-graphene nanocomposites in aqueous environment: Influence of environmental factors and UV irradiation. AB - The aggregation kinetics of TiO2-graphene nanocomposites in aqueous solution affected by solution pH, salt types (NaCl, CaCl2) and concentrations of electrolytes, and stability induced by UV irradiation was investigated in this study. The zeta potentials and hydrodynamic diameter of the nanoparticles were used as bases to assess the aggregation behavior, and stability of nanocomposites exposed to UV irradiation was expressed in terms of supernatant concentration. The aggregation of TiO2-graphene nanoparticles in aqueous media followed the colloidal theory. TiO2-graphene nanoparticles were significantly aggregated in the presence of a diavalent cation compared with monovalent cation because the former was more capable of effective charge screening and neutralization. The calculated Hamaker constant of the TiO2-graphene nanocomposites in aqueous solution prepared in the lab was 2.31*10(-20)J. The stability of this composite nanoparticles was between those of pure TiO2 and graphene. A known intensity of UV irradiation was beneficial in the formation of TiO2-graphene nanoparticle aggregates. However, prolonged UV irradiation may stabilize the nanoparticles. These results provided critical information about the colloidal properties of the new TiO2-graphene nanocomposites and were useful in predicting the fate and transport of TiO2-graphene nanocomposites in natural water environments. PMID- 26360461 TI - The effect of the morphology of supported subnanometer Pt clusters on the first and key step of CO2 photoreduction. AB - Using density functional theory calculations, we investigate the influence of size-dependent cluster morphology on the synergistic catalytic properties of anatase TiO2(101) surfaces decorated with subnanometer Pt clusters. Focusing on the formation of the key precursor in the CO2 photoreduction reaction (bent CO2( )), we find that flatter (2D-like) Pt clusters that "wet" the TiO2 surface offer significantly less benefit than 3D-like Pt clusters. We attribute the differences to three factors. First, the 3D clusters provide a greater number of accessible Pt-TiO2 interfacial sites with geometries that can aid CO2 bond bending and charge transfer processes. Second, binding competition among each Pt-CO2 bonding interaction mitigates maximum orbital overlaps, leading to insufficient CO2 binding. Third and also most interestingly, the 3D clusters tend to possess higher structural fluxionality than the flatter clusters, which is shown to correlate positively with CO2 binding strength. The preferred morphology adopted by the clusters depends on several factors, including the cluster size and the presence of oxygen vacancies on the TiO2 surface; this suggests a strategy for optimizing the synergistic effect between Pt clusters and TiO2 surfaces for CO2 photocatalysis. Clusters of ~6-8 atoms should provide the largest benefit, since they retain the desired 3D morphology, yet are small enough to exhibit high structural fluxionality. Electronic structure analysis provides additional insight into the electronic motivations for the enhanced binding of CO2 on TiO2 supported 3D Pt clusters, as well as suppressed binding on flattened, 2D-like clusters. PMID- 26360463 TI - Identification of tissue-restricted bioreaction suitable for in vivo targeting by fluorescent substrate library-based enzyme discovery. AB - Tissue-restricted bioreactions can be utilized to design chemical-biological tools and prodrugs. We have developed a fluorescent-substrate-library-based enzyme discovery approach to screen tissue extracts for enzymatic activities of interest. Assay-positive candidate proteins were identified by diced electrophoresis gel assay followed by peptide mass fingerprinting. We discovered that pyruvyl anilide is specifically hydrolyzed by carboxylesterase 2 (CES2), which is predominantly localized in the liver and kidney. We show that the pyruvyl targeting group/CES2 enzyme pair can be used to deliver the 7-amino-4 methylcoumarin fluorophore specifically to the liver and kidney in vivo. Our screening approach should be useful to find other masking group/enzyme pairs suitable for development of fluorescent substrates and prodrugs. PMID- 26360462 TI - An isomorphous replacement method for efficient de novo phasing for serial femtosecond crystallography. AB - Serial femtosecond crystallography (SFX) with X-ray free electron lasers (XFELs) holds great potential for structure determination of challenging proteins that are not amenable to producing large well diffracting crystals. Efficient de novo phasing methods are highly demanding and as such most SFX structures have been determined by molecular replacement methods. Here we employed single isomorphous replacement with anomalous scattering (SIRAS) for phasing and demonstrate successful application to SFX de novo phasing. Only about 20,000 patterns in total were needed for SIRAS phasing while single wavelength anomalous dispersion (SAD) phasing was unsuccessful with more than 80,000 patterns of derivative crystals. We employed high energy X-rays from SACLA (12.6 keV) to take advantage of the large anomalous enhancement near the LIII absorption edge of Hg, which is one of the most widely used heavy atoms for phasing in conventional protein crystallography. Hard XFEL is of benefit for de novo phasing in the use of routinely used heavy atoms and high resolution data collection. PMID- 26360464 TI - Graph Theoretical Analysis of BOLD Functional Connectivity during Human Sleep without EEG Monitoring. AB - BACKGROUND: Functional brain networks of human have been revealed to have small world properties by both analyzing electroencephalogram (EEG) and functional magnetic resonance imaging (fMRI) time series. METHODS & RESULTS: In our study, by using graph theoretical analysis, we attempted to investigate the changes of paralimbic-limbic cortex between wake and sleep states. Ten healthy young people were recruited to our experiment. Data from 2 subjects were excluded for the reason that they had not fallen asleep during the experiment. For each subject, blood oxygen level dependency (BOLD) images were acquired to analyze brain network, and peripheral pulse signals were obtained continuously to identify if the subject was in sleep periods. Results of fMRI showed that brain networks exhibited stronger small-world characteristics during sleep state as compared to wake state, which was in consistent with previous studies using EEG synchronization. Moreover, we observed that compared with wake state, paralimbic limbic cortex had less connectivity with neocortical system and centrencephalic structure in sleep. CONCLUSIONS: In conclusion, this is the first study, to our knowledge, has observed that small-world properties of brain functional networks altered when human sleeps without EEG synchronization. Moreover, we speculate that paralimbic-limbic cortex organization owns an efficient defense mechanism responsible for suppressing the external environment interference when humans sleep, which is consistent with the hypothesis that the paralimbic-limbic cortex may be functionally disconnected from brain regions which directly mediate their interactions with the external environment. Our findings also provide a reasonable explanation why stable sleep exhibits homeostasis which is far less susceptible to outside world. PMID- 26360467 TI - Track A. Biomaterials and Biocompatibility 1. PMID- 26360465 TI - PilG is Involved in the Regulation of Twitching Motility and Antifungal Antibiotic Biosynthesis in the Biological Control Agent Lysobacter enzymogenes. AB - Lysobacter enzymogenes strain C3 is a gliding bacterium which produces the antifungal secondary metabolite heat-stable antifungal factor (HSAF) and type IV pilus (T4P) as important mechanisms in biological control activity against fungal pathogens. To date, the regulators that control HSAF biosynthesis and T4P dependent twitching motility in L. enzymogenes are poorly explored. In the present study, we addressed the role of pilG in the regulation of these two traits in L. enzymogenes. PilG of L. enzymogenes was found to be a response regulator, commonly known as a component of a two-component transduction system. Mutation of pilG in strain C3 abolished its ability to display spreading colony phenotype and cell movement at the colony margin, which is indicative of twitching motility; hence, PilG positively regulates twitching motility in L. enzymogenes. Mutation of pilG also enhanced HSAF production and the transcription of its key biosynthetic gene hsaf pks/nrps, suggesting that PilG plays a negative regulatory role in HSAF biosynthesis. This finding represents the first demonstration of the regulator PilG having a role in secondary metabolite biosynthesis in bacteria. Collectively, our results suggest that key ecological functions (HSAF production and twitching motility) in L. enzymogenes strain C3 are regulated in opposite directions by the same regulatory protein, PilG. PMID- 26360466 TI - The effects of exogenous antioxidant germanium (Ge) on seed germination and growth of Lycium ruthenicum Murr subjected to NaCl stress. AB - In this paper, we present the results of a study on the effects of exogenous antioxidant germanium (Ge) on seed germination and seedling growth, and its role as a radical scavenger that regulates related enzymes, including superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT), under salt stress. Seeds were incubated in 0, 50, 100, 150, 200, 250 and 300 mM NaCl to determine the salt tolerance of the Lycium ruthenicum Murr seedlings and from the results, the critical and ultimate salt concentrations were chosen for the next experiment. Subsequently, two treatments (seeds soaked in Ge and Ge added to salt) with four concentrations of GeO2 (0, 5, 10 and 20 MUM) were used with the critical (150 mM) and ultimate salt concentrations (250 mM). The results demonstrated that salt alone inhibited seed germination significantly (>=150 mM) and reduced seedling growth (>=200 mM). The addition of exogenous Ge to the salt solution, as well as soaking the seeds in Ge, attenuated the salt stress effects in a manner dependent on the dose of Ge, as indicated by the increased percentage of seeds that germinated and improved seedling growth. The addition of Ge also showed a significant reversal of salt stress on the activities of antioxidant enzymes, with a decrease in SOD and POD activity, but an increase in CAT activity with 150 mM NaCl, and enhancement of SOD, POD and CAT with 250 mM NaCl. Correspondingly, the level of malondialdehyde was decreased significantly by each Ge treatment under salt stress. Further, for L. ruthenicum, adding 10 Ge and seeds soaked in 5 Ge were the most effective treatments. To our knowledge, this is the first report to show the protective effects of exogenous Ge against salt-induced oxidative damage in L. ruthenicum seed germination and seedling growth. Thus, L. ruthenicum can be used in areas with salty soil and Ge can promote the plants' salt tolerance. PMID- 26360468 TI - Track E. Cellular, Tissue and Bioengineering. PMID- 26360469 TI - Track F. Poster Session: New developments in monitoring. PMID- 26360470 TI - Track G. Devices and Systems for Surgical 1. PMID- 26360471 TI - Track I. Image Based Intervention. PMID- 26360472 TI - Track J. Poster Session: Image Processing. PMID- 26360473 TI - Track K. Imaging 1: MRI. PMID- 26360474 TI - Track L. Magnetic Methods in Medicine. PMID- 26360475 TI - Track M. FS: Closed loop control in medical technology. PMID- 26360476 TI - Track N. FS: LUMEN - Luebeck Medical Engineering. PMID- 26360477 TI - Track O. Biomechanical Modeling. PMID- 26360478 TI - Track B. FS: Computational optical coherence tomography and digital holography. PMID- 26360479 TI - Track P. Prevention and Rehabilitation Engineering. PMID- 26360480 TI - Track C. Nano- and Physikalischchemische Systeme. PMID- 26360481 TI - Track Q. Poster Session: Education and Training for Engineers and Physicians. PMID- 26360482 TI - Track R. Prosthetics and Implants 1: Structures and Design. PMID- 26360483 TI - Track S. Usability and Risk Management for Medical Devices. PMID- 26360485 TI - Track D. FS: New developments in the analysis and modification of central nervous rhythms. PMID- 26360484 TI - Track Z (FS). FS: Novel developments in the diagnosis and treatment of autoimmune blistering diseases. PMID- 26360487 TI - Assessment of the validity of self-reported smoking status among schoolchildren in Sousse, Tunisia. AB - INTRODUCTION: Tobacco use, which begins in adolescence and childhood and continues in later life, is the major avoidable risk for non-communicable diseases and death in the world. Self-reports have frequently been used to estimate smoking prevalence and health consequences. This study explores the validity of self-reports of smoking behavior among schoolchildren in Tunisia. MATERIALS AND METHODS: This study was conducted in March 2014 among a sample of 147 schoolchildren randomly selected. Data concerning the smoking habit were collected by a questionnaire designed for the purposes of this work. Then, exhaled CO, a biochemical marker of smoke exposure, was measured using piCO+ Smokerlyzer(r) breath CO monitor among participants. Sensitivity and specificity of self-reports were calculated. RESULTS: The prevalence of reported smoking was 9.5% with 16.7% and 1.7% respectively among boys and girls. Their mean age was 14.5+/-1.28 years old. When considering 4 ppm as the cut-off level of breath CO, sensitivity and specificity of self-reports were 100% and 93.7%, respectively. But at a breath CO cut-off of 3 ppm, self-reporting was 62.5% sensitive and 93.5% specific. CONCLUSION: According to our findings, we suggest that self-reports can be considered as a good tool to be used with a reasonable confidence to assess the smoking status. PMID- 26360488 TI - Is HEADS in our heads? Health risk behavior is not routinely discussed with young people with chronic conditions. AB - BACKGROUND: Outpatient clinic visits are a window of opportunity to address health risk behaviors and promote a healthier lifestyle among young people. The HEADS (Home, Education, Eating, Activities, Drugs [i.e. substance use including tobacco, alcohol, and illegal drugs], Sexuality [including contraception], Safety, Self-harm) interview is a feasible way of exploring health risk behaviors and resilience. OBJECTIVE: The purpose of this study was to evaluate how often HEADS topics were addressed according to young patients and staff in pediatric and adult outpatient clinics. METHODS: We conducted a questionnaire survey among young patients and health care professionals at a tertiary university hospital. Young patients reported on their cumulative experience and staff reported on their usual practice. RESULTS: A total of 290 young patients aged 12-22 years (78% having a chronic condition) and 97 health care professionals participated. We found only small reported differences between staff and young patients regarding whether home, education, and activity were addressed. However, staff reported twice the rate of addressing smoking, alcohol, illegal drugs, sexuality, and contraception compared to young patients. Young patients reported that smoking, alcohol, illegal drugs, sexuality, and contraception were addressed significantly more at adult clinics in comparison to pediatric clinics. After controlling for age, gender and duration of illness, according to young patients, adjusted odds ratios for addressing smoking at adult vs. pediatric clinics was 2.47 (95% confidence interval [CI]: 1.26-4.83), alcohol 2.84 (95% CI:1.45-5.57), illegal drugs 4.20 (95% CI:1.69-10.44), sexuality 3.54 (95% CI: 1.67-7.50), contraception 3.68 (95% CI:1.61-8.41), and any of the above 2.95 (95% CI: 1.47 5.91). CONCLUSION: According to young patients, smoking, alcohol, illegal drugs, sexuality, and contraception were not routinely addressed at a tertiary hospital, and especially at paediatric clinics, these issues were seldom addressed. PMID- 26360489 TI - The effectiveness of an adolescent reproductive health education intervention in Uganda. AB - Ugandan adolescents lack sufficient reproductive health knowledge, which accounts in part for the staggering rates of teen pregnancies and sexually transmitted (STI) infections in this population. This study aimed to (1) examine Ugandan adolescents' baseline STI and contraceptive knowledge; (2) determine whether this knowledge varies by demographic factors, prior sexual experience or school grade; and (3) evaluate the effectiveness of an educational program to increase and retain STI and contraceptive knowledge among Ugandan adolescents. This study surveyed 129 adolescents (ages 15-19) regarding knowledge of STIs and contraceptive methods at schools and community non-governmental organizations at three time points. Findings demonstrated that at baseline the mean test scores for contraceptive knowledge and STI knowledge were 44% and 72%, respectively. Participants in higher secondary school grade-levels had greater odds of having prior STI knowledge (OR=19.6, 95% CI 2.0-187.6); participants who had previously engaged in sex had greater odds of having prior contraceptive knowledge (OR=4.62, 95% CI 1.45-14.72). A higher grade level was not associated with better knowledge of contraception; and being sexually active was not associated with better knowledge of STI information. Participants' knowledge of STIs and contraceptives improved after the education session (p<0.001), and knowledge was retained 3 weeks later (p<0.001). Findings suggest that Ugandan adolescents do not have adequate education regarding contraceptive methods and that implementation of reproductive health modules by an outside party can be effective in improving knowledge. PMID- 26360490 TI - Challenges and results of a school-based intervention to manage excess weight among school children in Tunisia 2012-2014. AB - BACKGROUND: Obesity is a serious health issue and predisposes individuals to an increased risk of morbidity and mortality. Its prevalence in children has increased worldwide. OBJECTIVE: To demonstrate the feasibility and effectiveness of a school-based management program based on healthy lifestyle promotion for obese and overweight adolescents in Sousse, Tunisia. METHODS: We conducted a quasi-experimental study among overweight and obese school children enrolled in 7th and 8th grades in Sousse, Tunisia with two groups, intervention and control. The 1-year intervention was based on promoting healthy eating and physical activity through a collective intervention for all recruited children and an individual intervention only for obese children who require intensive managing. Data collection was done before, at the end and at a 4-month follow up of the intervention, both in intervention and control groups. RESULTS: The body mass index Z score decreased significantly from pre-intervention to post-intervention (1.89+/-0.57 to 1.76+/-0.63, p<0.001) and from post-intervention to the follow-up (1.76+/-0.63 to 1.55+/-0.68, p<0.001) in the intervention group. In the control group, it decreased significantly from pre-intervention to post-intervention but not significantly from post-intervention to follow-up assessment. Calorie intake decreased significantly both in intervention and control groups. CONCLUSION: This project began with introducing a new culture of health management in schools on one side and with increasing awareness of the importance of obesity prevention and treatment. The support of authorities for this type of action is very important to guarantee its sustainability. PMID- 26360491 TI - Determinants of cigarette smoking among school adolescents on the island of Java, Indonesia. AB - BACKGROUND: The Integrated Model of Change has successfully explained the behavior change process. Cigarette smoking is a social phenomenon, which needs to be understood for devising effective preventive strategies. OBJECTIVES: The study aims to apply the Integrated Model of Change to determine predictive factors of cigarette smoking behavior among school adolescents in Indonesia. METHODS: A school-based cross-sectional study was designed to collect data in Banten, Indonesia. A total of 698 students from eight high schools were recruited by multi-stage cluster sampling. The association between cigarette smoking and the independent variables was examined by multiple logistic regressions. RESULTS: The majority of respondents (86.4%) were between the ages of 15 and 17 years (Mean=16.4 years; SD=1.01). Approximately half (48.8%) of the students ever tried a cigarette while 29.6% were current smokers. Curiosity was reported as the main reason for experimenting with cigarettes (32%). The significant factors regarding current cigarette smoking were attitude [adjusted odds ratio (AOR)=2.68], social norms (AOR=12.80), self-efficacy (AOR=15.85), and accessibility (AOR=4.39). CONCLUSION: The study revealed social influence and self-efficacy that were strongly associated with cigarette smoking can help authorities in guiding possible intervention programs for school adolescents. PMID- 26360492 TI - Neurogenic speech sequelae following suicide attempt by hanging: a case report. AB - BACKGROUND: Attempting suicide by hanging has become one of the most preferred means among adolescents. Individuals who survive a suicide attempt by hanging have a range of deficits, including neuropsychological, neuropsychiatric, pulmonary and even speech and language deficits. Literature regarding speech and language deficits in cases of near hanging is especially limited. OBJECTIVE: This study aimed to demonstrate the sequelae of neurogenic speech deficits following a suicide attempt by hanging, the treatment strategies, and prognostic issues in one such case. METHODS: We report of Patient X who attempted suicide by hanging. The patient was admitted and a detailed speech and language evaluation was completed. RESULTS: Patient X was diagnosed with hypoxic-ischemic encephalopathy with organic amnesic syndrome. Consequent to the neurogenic insult, the patient demonstrated speech deficits that were characterized by moderate flaccid dysarthria and neurogenic stuttering. Patient X underwent a week of treatment, subsequent to which there was an improvement in certain speech subsystems. However, the neurogenic stuttering symptoms did not resolve completely even post therapy. CONCLUSION: Individuals who survive a suicide attempt by hanging have a range of deficits, including speech deficits that need to be addressed by a speech language pathologist. This case report is an eye opener for speech language pathologists regarding their role in such cases. PMID- 26360493 TI - Oral health impact, dental caries experience, and associated factors in 12-15 year-old school children in India. AB - BACKGROUND: Dental caries affects quality of life and has a negative impact on daily performance. OBJECTIVE: The study was conducted to assess the impact of oral health and its associated factors in schoolchildren in the age group 12-15 years in Indore, Madhya Pradesh. METHODS: A cross-sectional survey was conducted in schoolchildren in the age group 12-15 years. Sociodemographic and oral health related behaviors of schoolchildren were collected using a self-administered questionnaire. Child oral impact on daily performance (OIDP) questionnaire was used to assess the oral impacts. Oral examination was performed to check the presence of caries using decayed, missing and filled teeth (DMFT) index. RESULTS: A total of 690 schoolchildren participated in the survey. The mean age of the children was 13.58 years. The overall prevalence of dental caries was found to be 47.2%. The prevalence of one or more impact in the study population was 36.5%. The most prevalent impact was difficulty in eating and cleaning of teeth and the least prevalent impact were emotion and studying. Results of logistic regression analysis showed that the type of school that a child goes to, socioeconomic status, material used, dental visit, and dental caries were significantly associated with the Child-OIDP affected score. CONCLUSION: Oral health had a significant effect on the quality of life of schoolchildren. The prevalence of dental caries was found to be high. Effective policies need to be drafted for oral health promotion in this age group. PMID- 26360494 TI - The effects of educating mothers and girls on the girls' attitudes toward puberty health: a randomized controlled trial. AB - INTRODUCTION: The attitude of a girl toward her menstruation and puberty has a considerable impact on her role during motherhood, social adjustment, and future marital life. This study was conducted in 2014 with the aim of comparing the effects of educating mothers and girls on the attitudes of adolescent girls of Tabriz City, Iran, towards puberty health. METHODS: This randomized control clinical trial was conducted on 364 adolescent girls who experienced menstruation. Twelve schools were selected randomly among 107 secondary schools for girls. One-third of the students of each school were selected randomly using a table of random numbers and socio-demographic and each participant was asked to answer the attitude questionnaires. The schools were randomly allocated to the groups of mother's education, girl's education, and no-intervention. The attitude questionnaire was filled out by the participants again 2 months after intervention. The general linear model, in which the baseline values were controlled, was employed to compare the scores of the three groups after the intervention. RESULTS: No significant differences were observed among the three groups in terms of the attitude score before intervention (p>0.05). Attitude score improvement after intervention in the girl's education group was significantly higher than the one of both mother's education (adjusted mean difference [AMD]: 1.8; [95% confidence interval (CI): 0.4-1.3]) and no intervention groups (AMD: 1.3; [95% CI: 0.0-2.6]) by controlling the attitude score before intervention. CONCLUSION: Based on the findings, it is more effective to educate girls directly about puberty health to improve adolescent girls' attitudes than educating mothers and asking them to transfer information to the girls. Nevertheless, studies with longer training period and follow-up are proposed to determine the effects of educating girls (through their mothers) on their attitudes about puberty health. PMID- 26360495 TI - Lessons learned in building a hospital-wide transition program from pediatric to adult-based health care for youth with special health care needs (YSHCN). AB - Advancements in medicine have increased the likelihood that children with chronic illnesses will survive childhood. The success in treatment for their conditions has not been matched by methods to effectively facilitate their transition to adult care. This short report describes lessons learned in building a hospital wide health care transition (HCT) planning infrastructure that could help patients transition from pediatric to adult-based care regardless of disease/disability. A solid foundation on which to build a hospital-based HCT planning program includes the following: focusing on structure and processes needed to facilitate medical transition; conducting a baseline assessment of current transition policy/practice; building an understanding of the complexity and necessity of transition planning; identifying advocates for transition planning and adult providers who will accept youth with chronic medical conditions; and establishing methods to evaluate transition program building activities. The implementation of any HCT program will depend on creating a culture that expects successful HCT to be the culmination of successful pediatric care. Hospital support (resources, staff training and an expanded infrastructure into which the program can fit) is necessary for a sustainable HCT planning program. PMID- 26360486 TI - Clinical chorioamnionitis at term V: umbilical cord plasma cytokine profile in the context of a systemic maternal inflammatory response. AB - OBJECTIVE: Microbial invasion of the fetus due to intra-amniotic infection can lead to a systemic inflammatory response characterized by elevated concentrations of cytokines in the umbilical cord plasma/serum. Clinical chorioamnionitis represents the maternal syndrome often associated with intra-amniotic infection, although other causes of this syndrome have been recently described. The objective of this study was to characterize the umbilical cord plasma cytokine profile in neonates born to mothers with clinical chorioamnionitis at term, according to the presence or absence of bacteria and/or intra-amniotic inflammation. MATERIALS AND METHODS: A cross-sectional study was conducted, including patients with clinical chorioamnionitis at term (n=38; cases) and those with spontaneous term labor without clinical chorioamnionitis (n=77; controls). Women with clinical chorioamnionitis were classified according to the results of amniotic fluid culture, broad-range polymerase chain reaction coupled with electrospray ionization mass spectrometry (PCR/ESI-MS) and amniotic fluid interleukin (IL)-6 concentration into three groups: 1) no intra-amniotic inflammation; 2) intra-amniotic inflammation without detectable microorganisms; or 3) microbial-associated intra-amniotic inflammation. A fetal inflammatory response syndrome (FIRS) was defined as an umbilical cord plasma IL-6 concentration >11 pg/mL. The umbilical cord plasma concentrations of 29 cytokines were determined with sensitive and specific V-PLEX immunoassays. Nonparametric statistical methods were used for analysis, adjusting for a false discovery rate of 5%. RESULTS: 1) Neonates born to mothers with clinical chorioamnionitis at term (considered in toto) had significantly higher median umbilical cord plasma concentrations of IL-6, IL-12p70, IL-16, IL-13, IL-4, IL-10 and IL-8, but significantly lower interferon gamma (IFN-gamma) and tumor necrosis factor alpha (TNF)-alpha concentrations than neonates born to mothers with spontaneous term labor without clinical chorioamnionitis; 2) neonates born to mothers with clinical chorioamnionitis at term but without intra-amniotic inflammation had higher concentrations of IL-6, IL-12p70, IL-13, IL-4, IL-5, and IL-8, but lower IFN-gamma, than neonates not exposed to clinical chorioamnionitis, suggesting that maternal fever in the absence of intra-amniotic inflammation leads to a change in the fetal cytokine network; 3) there were significant, positive correlations between maternal and umbilical cord plasma IL-6 and IL-8 concentrations (IL-6: Spearman correlation=0.53; P<0.001; IL-8: Spearman correlation=0.42; P<0.001), consistent with placental transfer of cytokines; 4) an elevated fetal plasma IL-6 (>11 pg/mL), the diagnostic criterion for FIRS, was present in 21% of cases (8/38), and all these neonates were born to mothers with proven intra-amniotic infection; and 5) FIRS was associated with a high concentration of umbilical cord plasma IL-8, IL-10 and monocyte chemoattractant protein (MCP)-1. CONCLUSIONS: Neonates born to mothers with clinical chorioamnionitis at term had higher concentrations of umbilical cord plasma cytokines than those born to mothers without clinical chorioamnionitis. Even neonates exposed to clinical chorioamnionitis but not to intra-amniotic inflammation had elevated concentrations of multiple cytokines, suggesting that intrapartum fever alters the fetal immune response. PMID- 26360496 TI - Urinary myo-inositol levels in Japanese schoolchildren with normal glucose tolerance. AB - BACKGROUND: Urinary myo-inositol (UMI) level is elevated in adult diabetic patients, and also increases after glucose loading. However, the relationship between UMI and plasma glucose levels in children is unknown. We aimed to assess whether UMI is a practical marker for glucose intolerance in children or not. METHODS: In Study 1 (328 schoolchildren), fasting and postprandial UMI were measured, with DeltaUMI defined as the difference between fasting and postprandial UMI levels. In Study 2, oral glucose tolerance tests and UMI measurements were conducted in 18 children with suspected having diabetes. RESULTS: For Study 1, DeltaUMI was observed [-0.65 (-3.9, 1.35) mg/g creatinine]. For Study 2, children with diabetes or impaired glucose tolerance had a significantly higher DeltaUMI than children with normal glucose tolerance. CONCLUSIONS: These studies demonstrated the normal range of UMI in children and possibility of a novel biomarker for early detection of glucose intolerance in children. PMID- 26360497 TI - Synergistic and Dose-Controlled Regulation of Cellulase Gene Expression in Penicillium oxalicum. AB - Filamentous fungus Penicillium oxalicum produces diverse lignocellulolytic enzymes, which are regulated by the combinations of many transcription factors. Here, a single-gene disruptant library for 470 transcription factors was constructed and systematically screened for cellulase production. Twenty transcription factors (including ClrB, CreA, XlnR, Ace1, AmyR, and 15 unknown proteins) were identified to play putative roles in the activation or repression of cellulase synthesis. Most of these regulators have not been characterized in any fungi before. We identified the ClrB, CreA, XlnR, and AmyR transcription factors as critical dose-dependent regulators of cellulase expression, the core regulons of which were identified by analyzing several transcriptomes and/or secretomes. Synergistic and additive modes of combinatorial control of each cellulase gene by these regulatory factors were achieved, and cellulase expression was fine-tuned in a proper and controlled manner. With one of these targets, the expression of the major intracellular beta-glucosidase Bgl2 was found to be dependent on ClrB. The Bgl2-deficient background resulted in a substantial gene activation by ClrB and proved to be closely correlated with the relief of repression mediated by CreA and AmyR during cellulase induction. Our results also signify that probing the synergistic and dose-controlled regulation mechanisms of cellulolytic regulators and using it for reconstruction of expression regulation network (RERN) may be a promising strategy for cellulolytic fungi to develop enzyme hyper-producers. Based on our data, ClrB was identified as focal point for the synergistic activation regulation of cellulase expression by integrating cellulolytic regulators and their target genes, which refined our understanding of transcriptional-regulatory network as a "seesaw model" in which the coordinated regulation of cellulolytic genes is established by counteracting activators and repressors. PMID- 26360498 TI - Plasma cell and terminal B-cell differentiation in mantle cell lymphoma mainly occur in the SOX11-negative subtype. AB - Mantle cell lymphoma is a mature lymphoid neoplasm characterized by the t(11;14)(q13;q32) and cyclin D1 overexpression. SOX11 is a transcription factor commonly overexpressed in these tumors but absent in most other mature B-cell lymphomas whose function is not well understood. Experimental studies have shown that silencing of SOX11 in mantle cell lymphoma cells promotes the shift from a mature B cell into an early plasmacytic differentiation phenotype, suggesting that SOX11 may contribute to tumor development by blocking the B-cell differentiation program. The relationship between SOX11 expression and terminal B cell differentiation in primary mantle cell lymphoma and its relationship to the plasmacytic differentiation observed in occasional cases is not known. In this study we have investigated the terminal B-cell differentiation phenotype in 60 mantle cell lymphomas, 41 SOX11-positive and 19 SOX11-negative. Monotypic plasma cells and lymphoid cells with plasmacytic differentiation expressing cyclin D1 were observed in 7 (37%) SOX11-negative but in none of 41 SOX11-positive mantle cell lymphomas (P<0.001). Intense cytoplasmic expression of a restricted immunoglobulin light chain was significantly more frequent in SOX11-negative than -positive tumors (58 vs 13%) (P=0.001). Similarly, BLIMP1 and XBP1 expression was also significantly more frequent in SOX11-negative than in -positive cases (83 vs 34% and 75 vs 11%, respectively) (P=0.001). However, no differences in the expression of IRF4/MUM1 were observed among these subtypes of mantle cell lymphoma. In conclusion, these results indicate that SOX11-negative mantle cell lymphoma may be a particular subtype of this tumor characterized by more frequent morphological and immunophenotypic terminal B-cell differentiation features that may be facilitated by the absence of SOX11 transcription factor. PMID- 26360499 TI - Micronodular thymic neoplasms: case series and literature review with emphasis on the spectrum of differentiation. AB - We report nine cases of micronodular thymoma with lymphoid B-cell hyperplasia and one case of micronodular thymic carcinoma with lymphoid hyperplasia from our institution. For a better understanding of these rare tumors, clinical records, and histological features of these cases were reviewed, with detailed review of additional 64 literature cases of micronodular thymic neoplasms. The joint analysis identified 64 cases of micronodular thymoma with lymphoid B-cell hyperplasia and 9 cases of micronodular thymic carcinoma with lymphoid hyperplasia. Both groups revealed slight male predilection, with male:female ratio of 1.3:1 and 5:4, and occurred at >40 years of age, with a mean of 64 (41 83) and 62 (42-78) years, respectively. Myasthenia gravis was noted in 3/64 (5%) and 1/9 (11%) patients, respectively. Other systemic, disimmune, or hematologic disorders were noted in 6/64 (9%) and 1/9 (11%) patients, respectively. Components of conventional thymoma were reported in 11/64 (17%) micronodular thymomas with lymphoid B-cell hyperplasia, with transitional morphology between the two components in most of them. Cellular morphology was predominantly spindle in micronodular thymoma with lymphoid B-cell hyperplasia when specified (30/43), and epithelioid in micronodular thymic carcinoma with lymphoid hyperplasia (6/9), and cytological atypia was more encountered in the latter. Dedifferentiation/transformation from micronodular thymoma with lymphoid B-cell hyperplasia to micronodular thymic carcinoma with lymphoid hyperplasia seems to occur in a small subset of cases. Three cases of micronodular thymomas with lymphoid B-cell hyperplasia were described with co-existent low-grade B-cell lymphomas. Follow-up data were available for 30 micronodular thymomas with lymphoid B-cell hyperplasia and 6 micronodular thymic carcinomas with lymphoid hyperplasia, with a mean of 47 (0.2-180) months and 23 (3-39) months, respectively. Patients were alive without disease, except for five micronodular thymoma with lymphoid B-cell hyperplasia patients (dead from unrelated causes), and one micronodular thymic carcinoma with lymphoid hyperplasia patient (dead of disease). PMID- 26360500 TI - Safety and tolerability of antidepressant co-treatment in acute major depressive disorder: results from a systematic review and exploratory meta-analysis. AB - INTRODUCTION: Although antidepressant (AD) monotherapy is recommended first-line for major depressive disorder (MDD), AD + AD co-treatment is common. AREAS COVERED: We conducted the first systematic review searching PubMed/MEDLINE/PsycInfo/Embase from database inception until 1 June 2015 for acute randomized trials in >= 20 adults with MDD comparing AD monotherapy with AD + AD co-treatment that reported quantitative data on adverse events (AEs). Meta analyzing 23 studies (n = 2435, duration = 6.6 weeks) AD monotherapy and AD + AD co-treatment were similar regarding intolerability-related discontinuation (risk ratio [RR] = 1.38, 95% CI = 0.89 - 1.10) and frequency of >= 1 AE (RR = 1.19, 95% CI = 0.95 - 1.49). Nevertheless, AD + AD co-treatment was associated with significantly greater burden regarding 4/25 AEs (tremor: RR = 1.55, 95% CI = 1.01 - 2.38; sweating: RR = 1.95, 95% CI = 1.13 -3.38, >= 7% weight gain: RR = 3.15, 95% CI = 1.34 - 7.41; weight gain = 2.17, 95% CI = 0.71 - 3.63 kg), but not more CNS, gastrointestinal, sexual or alertness-related AEs. However, 11/25 AEs (44.0%) were reported in only 1 - 2 studies. Adding noradrenergic and specific serotonergic antidepressants (NaSSA) or tricyclic antidepressants (TCA) to selective serotonin reuptake inhibitors (SSRIs) was specifically associated with more AEs. EXPERT OPINION: The potential for increased AEs with AD + AD co treatment needs to be considered vis-a-vis unclear efficacy benefits of this strategy. In particular, NaSSAs and TCAs should be added to SSRIs with caution. Clearly, more data on side-effect burden of AD + AD co-treatment are needed. PMID- 26360502 TI - Renal AML with inferior vena cava thrombus treated by workbench surgery and autotransplantation. AB - Renal angiomyolipoma may sometimes require surgical intervention. In this paper, we present a case of renal angiomyolipoma which infiltrated the sinus and extended into the inferior vena cava. He was successfully treated with a combined approach of laparoscopic radical nephrectomy, extracorporeal workbench tumor resection, and autotransplantation. Three months postoperatively, no evidence of tumor recurrence or presence of thrombus in the inferior vena cava was noted. Our experience represents the successful application of a combined nephron-sparing approach in the management of angiomyolipoma with extension into a major blood vessel. PMID- 26360503 TI - What patients with addiction disorders need from their primary care physicians: A qualitative study. AB - BACKGROUND: Although strong relationships between primary care providers (PCPs) and patients with addictive disease are essential for care, these relationships are often strained. Providers frequently have negative attitudes about treating these patients, in part due to the practical and psychosocial challenges that come with addictive disease. Resulting hostility frequently causes avoidance of primary care by patients with potentially increased morbidity. However, gaining knowledge of patient perspectives on these relationships could improve physician attitudes toward patients with addictive disease and relatedly improve care. METHODS: The authors conducted 18 semistructured interviews of patients with current or prior debilitating addictive disease recruited from a primary care practice in East Baltimore. Interview transcripts were analyzed using editing analysis to reveal major themes. RESULTS: Participants elucidated several provider characteristics that were essential for successful relationships. Providers needed to be knowledgeable about addiction, feel responsible for treating these patients, emphasize overall health, and engage patients in their own care. Additionally, participants strongly desired providers who treated them as "people" that they cared about. Interestingly, interviewees also frequently cited patient characteristics that could affect the strength of patient-provider relationships. These included being concerned about their health, feeling deserving of care, and having appropriate psychiatric care for concomitant mental health conditions. Practical obstacles and a disorganized mindset impeded patient provider relationships. CONCLUSIONS: The interpersonal dynamics of the patient provider relationship are particularly important for patients with addictive disease, as this relationship may be one of the most stable and rewarding in their lives. Patients felt that greater understanding of the practical and psychosocial challenges of addiction enabled providers to more effectively address their health concerns and to be more caring and less judgmental. It is hoped that this work will contribute to providers' understanding of patients with addictions, thus allowing them to form stronger relationships and ultimately provide better care. PMID- 26360501 TI - Telmisartan to reduce cardiovascular risk in older HIV-infected adults: a pilot study. AB - BACKGROUND: HIV-infected persons are at increased cardiovascular disease (CVD) risk, but traditional CVD therapies are understudied in this population. Telmisartan is an angiotensin receptor blocker (ARB) and peroxisome proliferator activated receptor-gamma (PPAR-gamma) agonist that improves endothelial function and cardiovascular mortality in HIV-uninfected populations. We assessed the effects of telmisartan on endothelial function in older HIV-infected persons at risk for CVD in a small pilot study. METHODS: HIV-infected individuals>=50 years old on suppressive antiretroviral therapy (ART) with >=1 traditional CVD risk factor received open-label telmisartan 80 mg daily for 6 weeks. Brachial artery flow-mediated dilation (FMD) measured endothelial function. The primary endpoint was 6-week change in maximum relative FMD. RESULTS: Seventeen participants enrolled; 16 completed all evaluations (88% men, 65% non-White, median age 60 years, CD4+T lymphocyte count 625 cells/mm3). Antiretroviral therapy included 71% protease inhibitor (PI), 29% non-nucleoside reverse transcriptase inhibitor (NNRTI), 29% integrase inhibitor, 65% tenofovir, and 29% abacavir. Cardiovascular disease risk factor prevalence included 76% hyperlipidemia, 65% hypertension, 18% smoking, and 12% diabetes mellitus. After 6 weeks, statistically significant blood pressure changes were observed (systolic-16.0 mmHg, diastolic-6.0 mmHg) without significant changes in FMD. In subset analyses, FMD increased more among abacavir-treated, PI-treated, and non-smoking participants. CONCLUSIONS: No significant FMD changes were observed after 6 weeks of telmisartan therapy; however, abacavir- and PI-treated participants and non-smokers showed greater FMD increases. Additional studies are needed to explore the effects of telmisartan on endothelial function among HIV-infected individuals with traditional CVD and/or ART-specific risk factors. PMID- 26360504 TI - NLRP3 Deficiency Improves Angiotensin II-Induced Hypertension But Not Fetal Growth Restriction During Pregnancy. AB - Preeclampsia is a pregnancy-specific syndrome characterized by elevated blood pressure, proteinuria, and intrauterine growth restriction (IUGR). Although sterile inflammation appears to be involved, its pathogenesis remains unclear. Recent evidence indicates that sterile inflammation is mediated through the nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasomes, composed of NLRP3, apoptosis-associated speck like protein containing a caspase recruitment domain (ASC), and caspase-1. Here we investigated the role of the NLRP3 inflammasomes in the pathogenesis of preeclampsia using Nlrp3(-/-) and Asc(-/-) (Nlrp3 and Asc deficient) pregnant mice. During pregnancy in mice, continuous infusion of high-dose angiotensin II (AngII) induced hypertension, proteinuria, and IUGR, whereas infusion of low-dose AngII caused hypertension alone. AngII-induced hypertension was prevented in Nlrp3(-/-) mice but not in Asc(-/-), indicating that NLRP3 contributes to gestational hypertension independently of ASC-mediated inflammasomes. Although NLRP3 deficiency had no effect on IUGR, it restored the IL-6 up-regulation in the placenta and kidney of AngII-infused mice. Furthermore, treatment with hydralazine prevented the development of gestational hypertension but not IUGR or IL-6 expression in the placenta and kidney. These findings demonstrate that NLRP3 contributes to the development of gestational hypertension independently of the inflammasomes and that IUGR and kidney injury can occur independent of blood pressure elevation during pregnancy. PMID- 26360505 TI - Glucocorticoids Reset the Nasal Circadian Clock in Mice. AB - The symptoms of allergic rhinitis show marked day-night changes that are likely to be under the control of the circadian clock, but the mechanism of this control is poorly understood. Because most peripheral tissues have endogenous circadian clocks, we examined the circadian rhythm of the clock gene product PERIOD2 (PER2) in the nasal mucosa of male mice using a luciferase reporter and demonstrated for the first time the phase-dependent effects of dexamethasone (DEX) on nasal PER2 rhythm in vivo and ex vivo. The phase shifts in PER2 rhythm caused by DEX were observed around the peak phase of serum glucocorticoids, suggesting that the circadian rhythm of endogenous glucocorticoids regulates the peripheral clock of the mouse nasal mucosa. From the viewpoint of circadian physiology, the best time to administer intranasal steroid treatment for allergic rhinitis would be when no phase shift is caused by DEX: in the early evening in diurnal humans. PMID- 26360507 TI - Cost-effectiveness analysis of clinical smoking cessation interventions in Thailand. AB - AIMS: Clinical smoking cessation interventions have been found typically to be highly cost-effective in many high-income countries. There is a need to extend this to low- and middle-income countries and undertake comparative analyses. This study aimed to estimate the incremental cost-effectiveness ratio of a range of clinical smoking cessation interventions available in Thailand. METHODS: Using a Markov model, cost-effectiveness, in terms of cost per quality-adjusted life years (QALY) gained, from a range of interventions was estimated from a societal perspective for males and females aged 40 years who smoke at least 10 cigarettes per day. Interventions considered were: counselling in hospital, phone counselling (Quitline) and counselling plus nicotine gum, nicotine patch, bupropion, nortriptyline or varenicline. An annual discounting rate of 3% was used. Probabilistic sensitivity analyses were conducted and a cost-effectiveness acceptability curve (CEAC) plotted. Comparisons between interventions were conducted involving application of a 'decision rule' process. RESULTS: Counselling with varenicline and counselling with nortriptyline were found to be cost-effective. Hospital counselling only, nicotine patch and bupropion were dominated by Quitline, nortriptyline and varenicline, respectively, according to the decision rule. When compared with unassisted cessation, probabilistic sensitivity analysis revealed that all interventions have very high probabilities (95%) of being cost-saving except for nicotine replacement therapy (NRT) patch (74%). CONCLUSION: In middle-income countries such as Thailand, nortriptyline and varenicline appear to provide cost-effective clinical options for supporting smokers to quit. PMID- 26360506 TI - Voluntary Exercise Improves Estrous Cyclicity in Prenatally Androgenized Female Mice Despite Programming Decreased Voluntary Exercise: Implications for Polycystic Ovary Syndrome (PCOS). AB - Prenatal androgen (PNA) exposure in mice produces a phenotype resembling lean polycystic ovary syndrome. We studied effects of voluntary exercise on metabolic and reproductive parameters in PNA vs vehicle (VEH)-treated mice. Mice (8 wk of age) were housed individually and estrous cycles monitored. At 10 weeks of age, mice were divided into groups (PNA, PNA-run, VEH, VEH-run, n = 8-9/group); those in the running groups received wheels allowing voluntary running. Unexpectedly, PNA mice ran less distance than VEH mice; ovariectomy eliminated this difference. In ovary-intact mice, there was no difference in glucose tolerance, lower limb muscle fiber types, weight, or body composition among groups after 16 weeks of running, although some mitochondrial proteins were mildly up-regulated by exercise in PNA mice. Before running, estrous cycles in PNA mice were disrupted with most days in diestrus. There was no change in cycles during weeks 1-6 of running (10-15 wk of age). In contrast, from weeks 11 to 16 of running, cycles in PNA mice improved with more days in proestrus and estrus and fewer in diestrus. PNA programs reduced voluntary exercise, perhaps mediated in part by ovarian secretions. Exercise without weight loss improved estrous cycles, which if translated could be important for fertility in and counseling of lean women with polycystic ovary syndrome. PMID- 26360508 TI - Divergent Stereocontrolled Synthesis of the Enantiopure Tetracyclic Cores of Asparagamine A and Stemofoline via an Intramolecular 2-Propylidine-1,3 (bis)silane Bicyclization. AB - A concise and highly diastereoselective synthesis of the polyfused tetracyclic cores of the Stemona alkaloids asparagamine A and stemofoline that relies on a 2 propylidine-1,3-(bis)silane bicyclization onto a enantiodefined pyrrolidine 2,5 di(cation) equivalent derived from l-malic acid is reported. A crucial feature of this divergent synthetic approach involves the solvolysis of a transient and highly labile tertiary-propargylic hydroxylactam trifluoroacetate in the strongly ionizing medium 5 M LiClO4/Et2O. The acyliminium ion generated in this manner undergoes stereospecific interception by the aforementioned (bis)silane nucleophile. PMID- 26360509 TI - Global agricultural intensification during climate change: a role for genomics. AB - Agriculture is now facing the 'perfect storm' of climate change, increasing costs of fertilizer and rising food demands from a larger and wealthier human population. These factors point to a global food deficit unless the efficiency and resilience of crop production is increased. The intensification of agriculture has focused on improving production under optimized conditions, with significant agronomic inputs. Furthermore, the intensive cultivation of a limited number of crops has drastically narrowed the number of plant species humans rely on. A new agricultural paradigm is required, reducing dependence on high inputs and increasing crop diversity, yield stability and environmental resilience. Genomics offers unprecedented opportunities to increase crop yield, quality and stability of production through advanced breeding strategies, enhancing the resilience of major crops to climate variability, and increasing the productivity and range of minor crops to diversify the food supply. Here we review the state of the art of genomic-assisted breeding for the most important staples that feed the world, and how to use and adapt such genomic tools to accelerate development of both major and minor crops with desired traits that enhance adaptation to, or mitigate the effects of climate change. PMID- 26360511 TI - Recovery from food protein-induced enterocolitis syndrome caused by fish. PMID- 26360510 TI - [(11)C]Raclopride binding in the striatum of minimally restrained and free walking awake mice in a positron emission tomography study. AB - Anesthesia and restraint stress have profound impacts on brain functions, including neural activity and cerebrovascular function, possibly influencing functional and neurochemical positron emission tomography (PET) imaging data. For circumventing this effect, we developed an experimental system enabling PET imaging of free-walking awake mice with minimal restraints by fixing the head to a holder. The applicability of this system was investigated by performing PET imaging of D2 dopamine receptors with [(11)C]raclopride under the following three different conditions: (1) free-walking awake state; (2) 1.5% isoflurane anesthesia; and (3) whole-body restraint without anesthesia. [(11)C]raclopride binding potential (BP(ND)) values under isoflurane anesthesia and restrained awake state were significantly lower than under free-walking awake state (P < 0.01). Heart rates in restrained awake mice were significantly higher than those in free-walking awake mice (P < 0.01), suggesting that free-walking awake state minimized restraint stress during the PET scan. [(11)C] raclopride-PET with methamphetamine (METH) injection was also performed in awake and anesthetized mice. METH-induced reduction of [(11)C]raclopride BP(ND) in anesthetized mice showed a trend to be less than that in free-walking awake mice, implying that pharmacological modulation of dopaminergic transmissions could be sensitively captured by PET imaging of free-walking awake mice. We concluded that our system is of utility as an in vivo assaying platform for studies of brain functions and neurotransmission elements in small animals, such as those modeling neuropsychiatric disorders. PMID- 26360512 TI - A DNA-binding protein defines the precise region of chromosome capture during Bacillus sporulation. AB - During sporulation, Bacillus subtilis divides around the nucleoid near one cell pole, initially capturing approximately one quarter of one chromosome in the newly formed forespore compartment. While it is known that a specific region of the nucleoid is reproducibly captured in the forespore, the mechanism underlying the precision of capture is unknown. Here we describe a role for RefZ, a DNA binding protein that regulates FtsZ, and its cognate binding motifs (RBMs) in defining the specific region of chromosome initially captured in the forespore. RefZ is conserved across the Bacillus genus and remains functional as an inhibitor of cell division in a species-swapping experiment. The RBMs are also conserved in their positioning relative to oriC across Bacillus, suggesting that the function of the RBMs is both important and position-dependent in the genus. In B. subtilis, the RBMs flank the region of the chromosome captured at the time of cell division, and we find that RefZ binds the five oriC-proximal RBMs with similar apparent affinity in units of two and four. refZ and RBM mutants capture chromosomal regions normally excluded from the forespore, suggesting that RefZ RBM complexes play a role in regulating the position of cell division relative to the chromosome during sporulation. PMID- 26360514 TI - The ASPHO 2015 Distinguished Career Award Goes to Dr. Winfred C. Wang, MD. PMID- 26360516 TI - Syntheses and analytical characterizations of N-alkyl-arylcyclohexylamines. AB - The rise in new psychoactive substances that are available as 'research chemicals' (RCs) remains a significant forensic and legislative challenge. A number of arylcyclohexylamines have attracted attention as RCs and continue to be encountered, including 3-MeO-PCP, 3-MeO-PCE and 3-MeO-PCPr. These compounds are commonly perceived as ketamine-like dissociative substances and are believed to act predominantly via antagonism of the N-methyl-D-aspartate (NMDA) receptor. To aid in the identification of newly emerging substances of abuse, the current studies were performed. The syntheses of fifteen N-alkyl-arylcyclohexylamines are described. Analytical characterizations were performed via gas chromatography and high performance liquid chromatography coupled to multiple forms of mass spectrometry as well as nuclear magnetic resonance spectroscopy, ultraviolet diode array detection and infrared spectroscopy. The series consisted of the N alkyl derivatives (N-methyl, N-ethyl, N-propyl) of phenyl-substituted and isomeric 2-, 3- and 4-methoxy phenylcyclohexylamines, as well as the N-alkyl derivatives obtained from 3-methylphenyl and 2-thienyl moieties. In addition to the presentation of a range of previously unreported data, it was also found that positional isomers of aryl methoxyl-substituted arylcyclohexylamines were readily distinguishable under a variety of analytical conditions. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26360517 TI - Water-Soluble Fluorescent Probes for Selective Recognition of Lysine and Its Application in an Object Carry-and-Release System. AB - A water-soluble fluorescent probe PEG-TPA-5' was synthesized, which shows an excellent selectivity to detect Lys in aqueous phase. An object carry-and-release system is established by applying PEG-TPA-5' as carrier and Lys as chemical stimulating source. PMID- 26360518 TI - The effect of threat information on acquisition, extinction, and reinstatement of experimentally conditioned fear of movement-related pain. AB - OBJECTIVE: The experiential acquisition of pain-related fear has been demonstrated by pairing a painful electrocutaneous stimulus pain-US; unconditioned pain stimulus) with one movement (CS+; conditioned stimulus) but not with another (CS-). However, it is expected that during acquisition through direct experience, pain-related fear can be intensified or weakened by verbally/visually transmitted information about the pain and its meaning. METHOD: Participants received threatening information (US-inflation), safety information (US-deflation), or no information about the pain-US (US-same). Additionally, we measured return of fear after a reinstatement procedure: two unsignaled pain-USs were presented in the experimental groups, but not in the control groups. RESULTS: We replicated the acquisition and extinction of experimentally induced fear of movement-related pain in healthy subjects both in the verbal reports and the eye-blink startle measures. Two reinstating pain-US presentations led to a differential return of self-reported fear and a nondifferential return of fear in the eye-blink startle responses. Although, we failed to find an effect of verbal/visual information regarding the meaning of the pain-US on the acquisition, extinction, or reinstatement of pain-related fear, we did observe a pain sensitization effect over time suggesting that our threat manipulation induced an increase of perceived threat in all groups. CONCLUSION: The results suggest that our threat manipulation might not have worked or that it was not sensitive enough to yield group-specific effects. We replicated acquisition, extinction, and return of experimentally conditioned fear of movement-related pain, but the threat manipulation failed to generate any additional effects. PMID- 26360519 TI - Diagnostic Performance of Brain MRI in Immune Reconstitution Inflammatory Syndrome. AB - BACKGROUND AND PURPOSE: Central nervous system immune reconstitution inflammatory syndrome (CNS-IRIS) significantly negatively impacts the human immunodeficiency virus (HIV)-infected population on combination antiretroviral therapy (cART). We sought to determine the diagnostic performance of several magnetic resonance imaging (MRI) features for CNS-IRIS in a cohort of HIV+ patients recently started on cART. METHODS: Our radiologic database was searched from January 2003 to September 2014 retrospectively for patients diagnosed with HIV and worsening symptoms on cART. A total of 20 patients with HIV were identified; patients were classified as having CNS-IRIS on the basis of established clinical criteria (8 patients; 12 age- and sex-matched controls). Brain MR images were obtained at a single post-cART timepoint during hospitalization for acute neurologic deterioration and blindly interpreted by two experienced neuroradiologists for the presence of four variables: intrinsic T1 hyperintensity, marginal reduced diffusion, and marginal enhancement or perivascular enhancement. RESULTS: Although each individual finding showed moderate predictive accuracy, the combination of MR findings demonstrated good test characteristics: sensitivity 88% (confidence interval [CI] 62-98), specificity 79% (58-93), positive predictive value 71% (44-90%), and negative predictive value 83% (CI 52-98%). In addition, this final diagnosis demonstrated good predictive accuracy, area under curve .78 (CI .63-.91), and moderate inter-reader agreement, kappa = .55. CONCLUSIONS: Our findings suggest that although each individual MR finding shows only moderate diagnostic performance, the combined assessment of experienced neuroradiologists has good predictive accuracy. The absence of any described MRI findings makes the diagnosis of CNS-IRIS highly unlikely. PMID- 26360520 TI - Ligneous membranitis in Scottish Terriers is associated with a single nucleotide polymorphism in the plasminogen (PLG) gene. AB - Ligneous membranitis (LM) is a rare chronic inflammatory condition of the mucous membranes associated with plasminogen (encoded by PLG) deficiency in affected humans and dogs. In human, the condition is genetic in nature with numerous mutations and polymorphisms in PLG identified in affected individuals and related family members. The condition is uncommonly reported in dogs and, to date, no genetic studies have been performed. We identified related Scottish Terriers (littermates) with severe LM and unaffected relatives (sire, dam and a sibling from a previous litter). Plasma plasminogen activity was below normal in one affected dog but within normal reference intervals for the other. Sequencing of PLG from the affected dogs revealed a homozygous A>T single nucleotide polymorphism in an intron donor site (c.1256+2T>A). The related, unaffected dogs displayed heterozygous alleles at this position (c.1256+2T/A), whereas no mutation was detected in unaffected, non-related control dogs. This is the first report to identify gene polymorphisms associated with LM in dogs. PMID- 26360521 TI - Kuwanon-L as a New Allosteric HIV-1 Integrase Inhibitor: Molecular Modeling and Biological Evaluation. AB - HIV-1 integrase (IN) active site inhibitors are the latest class of drugs approved for HIV treatment. The selection of IN strand-transfer drug-resistant HIV strains in patients supports the development of new agents that are active as allosteric IN inhibitors. Here, a docking-based virtual screening has been applied to a small library of natural ligands to identify new allosteric IN inhibitors that target the sucrose binding pocket. From theoretical studies, kuwanon-L emerged as the most promising binder and was thus selected for biological studies. Biochemical studies showed that kuwanon-L is able to inhibit the HIV-1 IN catalytic activity in the absence and in the presence of LEDGF/p75 protein, the IN dimerization, and the IN/LEDGF binding. Kuwanon-L also inhibited HIV-1 replication in cell cultures. Overall, docking and biochemical results suggest that kuwanon-L binds to an allosteric binding pocket and can be considered an attractive lead for the development of new allosteric IN antiviral agents. PMID- 26360522 TI - Short-Term Total Hip Arthroplasty Outcomes in Patients With Psoriatic Arthritis or Psoriatic Skin Disease Compared to Patients With Osteoarthritis. AB - OBJECTIVE: Outcomes of total hip arthroplasty (THA) in patients with psoriasis have been poorly studied. This study was undertaken to assess whether patients with psoriatic arthritis (PsA) or those with cutaneous psoriasis (PsC) without evidence of inflammatory joint disease are at an increased risk for worse outcomes after THA as compared to patients with osteoarthritis (OA). METHODS: Among subjects in a prospective THA registry, PsA and PsC cases were identified by International Classification of Diseases, Ninth Revision codes, and all cases were matched with patients with OA as controls. Analyses were performed to identify predictors of poor postoperative pain or function. RESULTS: Of the 289 potential cases of PsA or PsC, 63 with PsA and 153 with PsC were validated. Self report data were available postoperatively from 75% of PsA patients, 69% of PsC patients, and 94% of OA controls. In total, 51% of PsA patients and 56% of PsC patients were male, compared to 45% of OA controls (P = 0.04). Body mass index was higher in those with PsA or PsC (P = 0.002 versus controls). There were no differences in race or education between the 3 groups. PsA patients and PsC patients had more comorbidities than OA controls. PsA patients were more likely than PsC patients and OA controls to be current or previous smokers. Moreover, 54% of PsA patients were being treated with biologics or nonbiologic disease modifying antirheumatic drugs, compared to 8% of PsC patients. There were no significant differences in pre- or postoperative Western Ontario and McMaster Universities OA Index scores for pain or function between the 3 groups. Short Form 36 mental component summary scores were significantly better in the OA controls, both pre- and postoperatively (P = 0.006 and P < 0.001, respectively, versus PsA or PsC). EuroQol 5-domain health-related quality of life scores were significantly worse postoperatively for those with PsA or PsC (P < 0.0001 versus OA controls). In regression analyses, neither PsA nor PsC were risk factors for worse THA outcomes. Satisfaction with the outcomes of THA was similarly high among all 3 groups (P = 0.54). CONCLUSION: Neither PsA nor PsC are risk factors for poor outcomes after THA. This is important information to convey to patients with either PsA or PsC who are contemplating surgical intervention with THA. PMID- 26360523 TI - Alkaline-Earth-Catalyzed Dehydrocoupling of Amines and Boranes. AB - Dehydrocoupling reactions between the boranes HBpin and 9 borabicyclo[3.3.1]nonane and a range of amines and anilines ensue under very mild reaction conditions in the presence of a simple beta-diketiminato magnesium n butyl precatalyst. The facility of the reactions is suggested to be a function of the Lewis acidity of the borane substrate, and is dictated by resultant pre equilibria between, and the relative stability of, magnesium hydride and borohydride intermediates during the course of the catalysis. PMID- 26360524 TI - Co-localization of growth QTL with differentially expressed candidate genes in rainbow trout. AB - We tested whether genes differentially expressed between large and small rainbow trout co-localized with familial QTL regions for body size. Eleven chromosomes, known from previous work to house QTL for weight and length in rainbow trout, were examined for QTL in half-sibling families produced in September (1 XY male and 1 XX neomale) and December (1 XY male). In previous studies, we identified 108 candidate genes for growth expressed in the liver and white muscle in a subset of the fish used in this study. These gene sequences were BLASTN aligned against the rainbow trout and stickleback genomes to determine their location (rainbow trout) and inferred location based on synteny with the stickleback genome. Across the progeny of all three males used in the study, 63.9% of the genes with differential expression appear to co-localize with the QTL regions on 6 of the 11 chromosomes tested in these males. Genes that co-localized with QTL in the mixed-sex offspring of the two XY males primarily showed up-regulation in the muscle of large fish and were related to muscle growth, metabolism, and the stress response. PMID- 26360525 TI - Emotion suppression, not reappraisal, predicts psychotherapy outcome. AB - OBJECTIVES: The aim of this study was to identify whether trait emotion regulation strategies predict successful or unsuccessful psychotherapy outcomes in cognitive behaviour therapy. METHODS: Three emotion regulation strategies (reappraisal, suppression, and externalizing behaviour) were assessed in 358 in- and outpatients. Patients were then grouped by therapy outcome. Emotion regulation strategies and confounding variables were entered as predictors in multinomial logistic regression analyses. RESULTS: Emotion suppression, but not reappraisal, was found to predict therapy outcomes for in- and outpatients, with patients high in suppression experiencing worse outcomes. Externalizing behaviour was only relevant in inpatient treatment. CONCLUSIONS: High suppression might be detrimental to psychotherapy outcome and should be assessed early on. Further research should investigate the influence of suppression on the mechanisms that facilitate change in psychotherapy. PMID- 26360526 TI - In situ vaccine, immunological memory and cancer cure. AB - As surgery is able to remove primary tumors and limit metastases, the major challenge in cancer management is the prevention of post-resection recurrence and metastases. From the immune point of view, tumor resection removes the supply of tumor antigens that maintain an active concomitant antitumor immunity elicited by the primary tumor, and may also signal for deposition of immunological memory against future metastases. However, the natural course of this antitumor immunity in many cancer patients following complete tumor resection may not be favorable because protection is often lost after 1-3 years. Recent studies suggest that chemotherapy is able to activate this pre-existing antitumor immunity, and tumor resection following immune activation may lead to higher levels of immunological memory against future tumor antigens (in the form of metastases). Interleukin-12 added to chemotherapy mimics the function of a vaccine adjuvant in that it helps to enhance the antitumor immunity activated by chemotherapy and leaves a much stronger antitumor immune memory. This finding, when applied to cancer management, may help to maintain a strong and long lasting antitumor immunity following complete tumor resection, thus eliminating post-surgery recurrence and metastases. PMID- 26360527 TI - Respiratory Tract Infection Clinical Trials from 2007 to 2012. A Systematic Review of ClinicalTrials.gov. AB - RATIONALE: Respiratory tract infections are highly prevalent and variable, and confer considerable morbidity and mortality. There is a growing need for new treatments for such infections, particularly in the setting of worsening antibacterial resistance. OBJECTIVES: We analyzed data from ClinicalTrials.gov to summarize activity in respiratory infection trials, identify gaps in research activity, and inform efforts to address disparities between antimicrobial resistance and development of new antibacterial drugs. METHODS: We examined 69,779 interventional trials registered with ClinicalTrials.gov from 2007 to 2012, focusing on study conditions and interventions to identify respiratory infection-related trials. Programmatic identification with manual confirmation yielded 6,253 infectious disease trials, 1,377 respiratory infection trials, and 270 lower respiratory tract infection trials for analysis. MEASUREMENTS AND MAIN RESULTS: The 1,377 respiratory infection trials accounted for 2% of all trials and 22% of infectious diseases trials. Such trials (54.8%) were more likely than either nonrespiratory infectious diseases trials (48.1%) or noninfectious disease trials (42.8%) to receive industry funding. Stratification of respiratory infection trials by registration year demonstrated declining industry funding: 181 (64.9%) in 2007-2008 to 110 (46.0%) in 2011-2012. Respiratory infection trials more frequently evaluated vaccines (52.7 vs. 15.5% of nonrespiratory tract infection trials). Lower respiratory tract infection trials (excluding tuberculosis) focused primarily on bacterial pathogens (78.5%) followed by viral (12.6%), fungal (5.6%), and nontuberculous mycobacterial (3.0%) pathogens. Approximately 40% of 120 lower respiratory tract infection trials that were completed or terminated published results in the literature. On multivariable logistic regression analysis, a treatment focus was associated with decreased odds of publishing results (odds ratio, 0.28; 95% confidence interval, 0.10-0.82; P = 0.02). There were also generally low numbers of studies evaluating novel antimicrobial agents (community-acquired pneumonia, 15.9%; hospital-acquired pneumonia, 16.7%; ventilator-associated pneumonia, 5.3%). CONCLUSIONS: From 2007 to 2012, respiratory infection trials did not occur in numbers commensurate with global impact. The number of trials registered per year did not increase throughout the study period, partly due to declining industry support. There was a concerning reduction in prevention-oriented lower respiratory infection trials and an overall low number of such trials involving novel antimicrobials. PMID- 26360528 TI - Effects of cadmium on the cuttlefish Sepia pharaonis' arginine kinase: unfolding kinetics integrated with computational simulations. AB - Arginine kinase is closely associated with adaptation to environmental stresses such as high salinity and heavy metal ion levels in marine invertebrates. In this study, the effects of Cd(2+) on the cuttlefish Sepia pharaonis' arginine kinase (SPAK) were investigated. SPAK was isolated from the muscles of S. pharaonis and upon further purification, showed a single band on SDS-PAGE. Cd(2+) effectively inactivated SPAK, and the double-reciprocal kinetics indicated that Cd(2+) induced non-competitive inhibition of arginine and ATP. Spectrofluorometry results showed that Cd(2+) induced tertiary structure changes in SPAK with the exposure of hydrophobic surfaces that directly induced SPAK aggregation. The addition of osmolytes, glycine, and proline successfully blocked SPAK aggregation and restored the conformation and activity of SPAK. Molecular dynamics simulations involving SPAK and Cd(2+) showed that Cd(2+) partly blocks the entrance of ATP to the active site, and this result is consistent with the experimental results showing Cd(2+)-induced inactivation of SPAK. These results demonstrate the effect of Cd(2+) on SPAK enzymatic function and unfolding, including aggregation and the protective effects of osmolytes on SPAK folding. This study provides concrete evidence of the toxicity of Cd(2+) in the context of the metabolic enzyme SPAK, and it illustrates the toxic effects of heavy metals and detoxification mechanisms in cuttlefish. PMID- 26360529 TI - Cross-sectional study of alteration of phantom limb pain with visceral stimulation in military personnel with amputation. AB - While phantom limb pain is a well-recognized phenomenon, clinical experience has suggested that the augmentation of phantom limb pain with visceral stimulation is an issue for many military personnel with amputation (visceral stimulation being the sensation of the bowel or bladder either filling or evacuating). However, the prevalence of this phenomenon is not known. The aim of this study was to investigate the prevalence of the alteration in phantom limb pain and the effect that visceral stimulation has on phantom limb pain intensity. A cross-sectional study of 75 military personnel who have lost one or both lower limbs completed a questionnaire to assess the prevalence of the alteration of phantom limb pain with visceral stimulation. Included in the questionnaire was a pain visual analog scale (VAS) graded from 0 to 10. Patients recorded the presence and intensity of phantom limb pain. They also recorded whether and how this pain altered with a need to micturate or micturition, and/or a need to defecate or defecation, again using a pain VAS. Time since amputation, level of amputation, and medications were also recorded. Patients reported a phantom limb pain prevalence of 85% with a mean VAS of 3.6. In all, 56% of patients reported a change in the severity of phantom limb pain with visceral stimuli. The mean increase in VAS for visceral stimulation was 2.5 +/- 1.6 for bladder stimulation and 2.9 +/- 2.0 for bowel stimulation. Of the patients questioned, 65% reported an improvement in symptoms over time. VAS scores were highest in the subgroup less than 6 mo postamputation. An increase in phantom limb pain with visceral stimulation is a common problem for military personnel with amputation. PMID- 26360531 TI - Assessment of shoulder active range of motion in prone versus supine: a reliability and concurrent validity study. AB - BACKGROUND: As swimming and surfing are prone dominant sports, it would be more sport specific to assess shoulder active range of motion in this position. OBJECTIVES: To determine the reliability of the inclinometer and HALO(c) for assessing shoulder active range of motion in supine and prone and the concurrent validity of the HALO(c). Concurrent validity is based on the comparison of the HALO(c) and inclinometer. To determine if active range of motion (AROM) differences exists between prone and supine when assessing shoulder internal (IR) and external rotation (ER). DESIGN: The design included clinical measurement, reliability and validity. METHODS: Thirty shoulders (mean age = 26.8 years) without pathology were evaluated. Measurements were taken in supine and prone with both an inclinometer and HALO(c) device. RESULTS: Active ER ROM in prone was significantly higher than in supine when using both devices. Intra-rater reliability (within and between session) intraclass correlation coefficient (ICC) values ranged between 0.82-0.99 for both devices in supine and prone. An ICC test revealed a significant (p < 0.01) correlation for both devices in IR and ER movements (ICC3,1 = 0.87 and ICC3,1 = 0.72), respectively. CONCLUSION: This study has shown prone assessment of active ER and IR ROM to be a reliable and appropriate method for prone dominant athletes (swimmers and surfers). In this study greater ER ROM was achieved in prone compared to supine. This finding highlights the importance of standardizing the test position for initial and follow up assessments. Furthermore the HALO PMID- 26360530 TI - Association of Elevations of Specific T Cell and Monocyte Subpopulations in Rheumatoid Arthritis With Subclinical Coronary Artery Atherosclerosis. AB - OBJECTIVE: Coronary artery disease (CAD) is the leading cause of excess deaths in rheumatoid arthritis (RA). However, identification of features denoting patients with a risk of developing CAD is lacking. The composition of circulating peripheral blood mononuclear cell (PBMC) subsets in RA patients differs markedly from that in healthy controls with regard to the extent of T cell activation, with clonal expansion and differentiation to effector memory status, and presence of inflammatory monocytes. In this study, we sought to evaluate whether elevations in these PBMC subpopulations in RA patients could denote those with an increased risk of subclinical CAD, as determined by the presence of coronary artery calcification (CAC). METHODS: The study cohort comprised 72 patients with RA who underwent cardiac computed tomography to assess CAC. PBMC subsets were determined by multiparameter flow cytometry. Multivariable logistic regression was used to determine the associations between PBMC subpopulations and the presence of CAC. RESULTS: Among the 72 patients with RA, 33% had CAC and exhibited significant increases in the levels of circulating CD4 T cell subsets denoting activation and differentiation to the effector memory phenotypes. Analogous increases in the levels of CD8 T cell subsets, as well as in the CD14(high)CD16+ intermediate monocyte subset, were also present in these patients, as compared to those without CAC. The increases in the CD4 and CD8 T cell subsets were highly intercorrelated, whereas the increases in CD14(high)CD16+ monocytes were independent of elevations in the CD4 T cell subsets. After adjustments for relevant confounders, the levels of CD4+CD56+CD57+ T cells and CD14(high)CD16+ monocytes remained associated with the presence of CAC. CONCLUSION: These findings indicate that PBMC subsets are markers for the presence of CAC and suggest that mechanisms of atherogenesis in RA may operate in part through the elevations in these subsets, raising further questions about the mechanisms underlying the presence of such alterations in cell composition in patients with RA and the potential for shared etiologic pathways between RA and cardiovascular disease. PMID- 26360532 TI - Unusual Air Filters with Ultrahigh Efficiency and Antibacterial Functionality Enabled by ZnO Nanorods. AB - Porous membranes/filters that can remove airborne fine particulates, for example, PM2.5, with high efficiency at low energy consumption are of significant interest. Herein, we report on the fabrication of a new class of unusual superior air filters with ultrahigh efficiency and an interesting antibacterial functionality. We use atomic layer deposition (ALD) to uniformly seed ZnO on the surface of expanded polytetrafluoroethylene (ePTFE) matrix, and then synthesize well-aligned ZnO nanorods with tunable widths and lengths from the seeds under hydrothermal conditions. The presence of ZnO nanorods reduces the effective pore sizes of the ePTFE filters at little expense of energy consumption. As a consequence, the filters exhibit exceptional dust removal efficiencies greater than 99.9999% with much lower energy consumption than conventional filters. Significantly, the presence of ZnO nanorods strongly inhibits the propagation of both Gram positive and negative bacteria on the filters. Therefore, the functionalized filters can potentially overcome the inherent limitation in the trade-off effect and imply their superiority for controlling indoor air quality. PMID- 26360533 TI - Heart Rate As a Biomarker in Heart Failure: Role of Heart Rate Lowering Agents. AB - Heart failure (HF) is a common clinical condition affecting more than 5.8 million people in the United States, it remains the leading cause of death in the United States and worldwide. Ongoing challenges for biomarker identification include the need for objective assessment, measurement precision, and meaningful replication. Biomarkers not only serve as traditional predictors of prognosis, they can also help to identify high-risk patients who need closer monitoring and more aggressive therapy; therefore, we reviewed the use of heart rate (HR) as a biomarker in HF both of diagnostic and prognostic values, in addition, to being easily detected. HR is a determinant of myocardial oxygen demand, coronary blood flow, and myocardial performance and is central to the adaptation of cardiac output to metabolic needs. Increased HR is known to predict adverse outcome in the general population and in patients with chronic HF. Part of the ability of HR to predict risk is related to the forces driving it, namely, neurohormonal activation. We reviewed therapies, which slow the HR like beta-blockers and ivabradine (a drug that is a pure HR-reducing agent), and all the clinical studies suggest the benefit of these drugs in the management of HF, and increasing evidence suggests HR as a biomarker of both diagnostic and prognostic values in HF. PMID- 26360534 TI - Pustular Psoriasis of Pregnancy Successfully Treated With Cyclosporine. AB - Pustular psoriasis of pregnancy is a rare, autoimmune inflammatory disorder, which can be associated with adverse maternal and fetal outcomes. Although recovery of the skin lesions after the delivery is the rule, some patients need immunosuppressive treatment mainly with corticosteroids. We describe a patient with pustular psoriasis of pregnancy who needed treatment with cyclosporine for resistant skin psoriasis and systemic inflammatory response. PMID- 26360536 TI - First-Person Long-term Follow-up Using Autologous Mosaicplasty for Osteochondral Lesion Accompanying Femoral Head Fracture. AB - I present my perspective as a patient and surgeon on complete functional recovery after a devastating hip injury. This report represents the longest follow-up in the literature for autologous osteochondral mosaicplasty to treat an osteochondral defect associated with a femoral head fracture. I was 21 years old when I fractured my hip in a skiing accident. Days after immediate reduction, arthroscopy was attempted but converted to open reduction internal fixation with osteochondral autograft for a type II Pipkin fracture and associated osteochondral injury. Joint preservation was intended to delay hip replacement that was forecasted within a decade given the extent of disease. Thirteen years later, I remain pain-free with a Harris hip score of 100. I perform surgery daily and enjoy long-distance running despite radiographic follow-up at 8 years that demonstrated evolving degenerative change. Because of the incongruity of pain, function, and radiologic findings, I hesitate to obtain additional imaging. I prefer to remain ignorant of the radiologic status of my hip joint, relying instead on prospective pain and impairment. My experience illustrates that full recovery and return-to-sport can be achieved and persist for years. The relevance of imaging after joint preservation surgery is questionable in the absence of symptoms. LEVEL OF EVIDENCE: Therapeutic Level V. See Instructions for Authors for a complete description of levels of evidence. PMID- 26360535 TI - Segmentation of the thalamus based on BOLD frequencies affected in temporal lobe epilepsy. AB - OBJECTIVE: Temporal lobe epilepsy is associated with functional changes throughout the brain, particularly including a putative seizure propagation network involving the hippocampus, insula, and thalamus. We identified a specified frequency range where functional connectivity in this network was related to duration of disease. Then, to identify specific thalamic nuclei involved in seizure propagation, we determined the subregions of the thalamus that have increased resting functional oscillations in this frequency range. METHODS: Resting-state functional magnetic resonance imaging (fMRI) was acquired from 20 patients with unilateral temporal lobe epilepsy (TLE; 14 right and 6 left) and 20 healthy controls who were each age and gender matched to a specific patient. Wavelet-based fMRI connectivity mapping across the network was computed at each frequency to determine those frequencies where connectivity significantly decreases with duration of disease consistent with impairment due to repeated seizures. The voxel-wise power of the spontaneous blood oxygenation fluctuations of this frequency band was computed in the thalamus of each subject. RESULTS: Functional connectivity was impaired in the proposed seizure propagation network over a specific range (0.0067-0.013 Hz and 0.024-0.032 Hz) of blood oxygenation oscillations. Increased power in this frequency band (<0.032 Hz) was detected bilaterally in the pulvinar and anterior nucleus of the thalamus of healthy controls, and was increased over the ipsilateral thalamus compared to the contralateral thalamus in TLE. SIGNIFICANCE: This study identified frequencies of impaired connectivity in a TLE seizure propagation network and used them to localize the anterior nucleus and pulvinar of the thalamus as subregions most susceptible to TLE seizures. Further examinations of these frequencies in healthy and TLE subjects may provide unique information relating to the mechanism of seizure propagation and potential treatment using electrical stimulation. PMID- 26360537 TI - Value of a Dedicated Saturday Orthopaedic Trauma Operating Room. AB - OBJECTIVES: To determine the effect of an additional scheduled operative day on length of stay, distribution of caseload, waiting time to surgery, and direct variable hospital costs. DESIGN: Retrospective chart review. SETTING: Urban level 1 trauma center. PATIENTS: Consecutive operative tibia and femur fractures admitted from November 1, 2009, to October 31, 2011. INTERVENTION: Addition of a dedicated Saturday orthopaedic trauma operating room. MAIN OUTCOME MEASUREMENTS: Length of stay, distribution of caseload, and waiting time to surgery. RESULTS: The overall length of stay for all trauma patients admitted with femur or tibia fractures was significantly reduced by 2.7 days from a mean of 14.0-11.3 days (P value 0.018). Additionally, there was a trend toward shorter waiting time to surgery (average reduction of 25.1 hours) for patients admitted on a Friday (48.6 vs. 23.5 hours, P value 0.06). Furthermore, there was an increase in the number of cases performed on Saturdays by 59% (6.2% of the total caseload), whereas the originally disproportionally high number of cases on Mondays was appropriately reduced by 33% (6.7% of the total caseload). The estimated direct variable cost savings per year for the hospital was $1.13 million. CONCLUSIONS: Overall, these findings support the continuation of a dedicated Saturday orthopaedic trauma operating room and can provide the foundation for other departments with similar circumstances to negotiate for more dedicated operative time on weekends to improve efficiency. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence. PMID- 26360538 TI - Reduction of Radiation Exposure From C-Arm Fluoroscopy During Orthopaedic Trauma Operations With Introduction of Real-Time Dosimetry. AB - OBJECTIVES: The use of fluoroscopy for indirect guidance in orthopaedic trauma surgery has increased. The purpose of this investigation was to assess how real time visualization of radiation exposure impacts dose levels during orthopaedic trauma operations. DESIGN: Observational comparative study. SETTING: Level 1 trauma center orthopaedic trauma surgery operating room. PATIENTS/PARTICIPANTS: The participants in this study were 83 patients with fractures of the ankle, tibia, femur, or acetabulum receiving definitive surgical fixation of their fracture; children under 18 years of age were excluded from the study. Fellowship trained orthopaedic trauma surgeons, resident orthopaedic surgeons, radiology technicians, and scrub nurses involved in the operations on included fracture patients were also participants. INTERVENTION: Real-time radiation exposure feedback from the Philips DoseAware device. MAIN OUTCOME MEASUREMENTS: Radiation exposure from fluoroscopy compared between phase 1, during which participants were blinded to exposure levels, and phase 2, during which participants were able to see exposure levels in real time. RESULTS: Overall mean radiation exposure was decreased by 60% in phase 2 compared with phase 1 (P = 0.023). Mean surgeon (MS; average of primary and assistant surgeon) and mean nonsurgeon personnel (average of x-ray technician, scrub nurse, and patient) radiation exposures were decreased from phase 1 to phase 2, by 58% and 80%, respectively (MS, P = 0.034; mean nonsurgeon personnel, P = 0.043). From phase 1 to phase 2, MS radiation for femoral shaft fractures decreased by 80% or 162.0 MUSv (P = 0.02) and by 81% or 128.9 MUSv (P = 0.014) for acetabular fractures. DISCUSSION: Our data demonstrate that real-time visualization of radiation exposure during orthopaedic trauma operations can decrease radiation exposure in the highest exposure cases. Further research is necessary to determine whether the reduction in radiation exposure is sustained over time and to understand how real-time radiation exposure data mitigates exposure. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence. PMID- 26360539 TI - Improved Survival After Pelvic Fracture: 13-Year Experience at a Single Trauma Center Using a Multidisciplinary Institutional Protocol. AB - OBJECTIVES: To analyze pelvic fracture mortality rates before and after initiation of a multidisciplinary pelvic fracture protocol. DESIGN: Retrospective database analysis. SETTING: Prospective data from our Level-I National Trauma Registry of The American College of Surgeons (NTRACS) database. PATIENTS/PARTICIPANTS: A total of 1682 trauma patients with pelvic fractures from 2000 to 2013 were compared with a control group of 42,629 without pelvic fractures. INTERVENTION: Initiation of a multidisciplinary institutional protocol to guide the initial management of trauma patients with pelvic fractures. MAIN OUTCOME MEASUREMENTS: Patients were grouped into 3 periods (group 1: 2000-2003, group 2: 2004-2007, group 3: 2008-2013). Multivariate logistic regression analysis was conducted to assess associations between mortality and age, shock (systolic blood pressure less than or equal to 90 mm Hg), head injury (Glasgow Coma Scale less than or equal to 8), Injury Severity Score (ISS), and time period. RESULTS: Unadjusted mortality rates decreased [12.5%-11.0% (P = 0.72)]; however, ISS increased [19.1-22.7 (P < 0.01)]. Age, shock, head injury, increasing ISS, and earlier period were significantly associated with mortality. Adjusted mortality decreased over time [odds ratio for 2000-2003 vs. 2008-2013: 2.05, 95% confidence interval = (1.26, 3.33) and odds ratio for 2004-2007 vs. 2008-2013: 1.71, 95% confidence interval = (1.09, 2.67)]. From 2000 to 2003, an unstable fracture pattern in the healthiest cohort significantly increased mortality compared with the stable fracture pattern cohort (8.6% and 0.0%, P < 0.01). In subsequent intervals, there was no statistically significant association between stable versus unstable fracture patterns and mortality. CONCLUSIONS: Adjusted pelvic fracture mortality rates have significantly decreased over time. In the healthiest patients with unstable pelvic fractures, the mortality rate is now similar to that of patients with stable fracture patterns. With sustained institutional effort to address pelvic fractures, mortality rates can be diminished. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence. PMID- 26360540 TI - Preoperative Testing for Hip Fracture Patients Delays Surgery, Prolongs Hospital Stays, and Rarely Dictates Care. AB - OBJECTIVES: To determine how often preoperative testing is requested for geriatric hip fracture patients, to assess the extent to which preoperative testing is associated with delayed surgery, and to measure the frequency with which preoperative testing changes patient management. DESIGN: Retrospective. SETTING: Academic health system. PATIENTS: Two hundred fifty consecutive geriatric hip fracture patients admitted through the emergency department and underwent surgery. INTERVENTION: Hip fracture surgery. MAIN OUTCOME MEASUREMENTS: The patients were categorized according to whether additional preoperative tests were requested. For each patient, the times of presentation and surgery were recorded, yielding a "time-to-surgery interval." The results of any tests, the actions resulting from testing, and the length of hospital stay were also noted. RESULTS: Additional preoperative testing was performed for 67 patients (27%). For those patients, the mean time-to-surgery was 73 hours. For the 183 patients who had no testing, the mean time-to-surgery was 37 hours. Moreover, 42 of the 67 patients with testing (63%) had time-to-surgery greater than 48 hours, compared with only 37 of the 183 (20%) patients without testing. The mean length of stay for tested patients was 12.0 days compared with 9.0 days for nontested patients. In only 2 of the 67 tested patients was further care offered based on the test result. CONCLUSIONS: Testing was associated with greater time-to-surgery and length of stay. Furthermore, testing rarely influenced management. Patients might be able to have surgery more expeditiously and leave the hospital earlier if testing were deferred. LEVEL OF EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence. PMID- 26360541 TI - The Utility of Digital Tomosynthesis to the Practicing Orthopaedic Trauma Surgeon: A Case Series. AB - OBJECTIVE: To document the role of digital tomosynthesis (DTS) in the evaluation and treatment of orthopaedic trauma patients. DESIGN: Retrospective case series. SETTING: Level 1 trauma center with nonunion referral patient population. PARTICIPANTS: Four orthopaedic trauma patients with musculoskeletal injuries. INTERVENTION: Three revision surgical procedures and 1 conservative treatment for patients with periprosthetic fractures or nonunions. RESULTS: DTS successfully visualized 2 nonunions, 1 refracture, and 1 arthrodesis. MAIN OUTCOME MEASURE: Documented fracture or nonunion on imaging. CONCLUSIONS: DTS has the potential to be of significant value in the detection and follow-up of fractures. LEVEL OF EVIDENCE: Diagnostic Level IV. See Instructions for Authors for a complete description of levels of evidence. PMID- 26360542 TI - Early Complications and Outcomes in Combat Injury-Related Invasive Fungal Wound Infections: A Case-Control Analysis. AB - OBJECTIVE: Clinicians have anecdotally noted that combat-related invasive fungal wound infections (IFIs) lead to residual limb shortening, additional days and operative procedures before initial wound closure, and high early complication rates. We evaluated the validity of these observations and identified risk factors that may impact time to initial wound closure. DESIGN: Retrospective review and case-control analysis. SETTING: Military hospitals. PATIENTS/PARTICIPANTS: US military personnel injured during combat operations (2009-2011). The IFI cases were identified based on the presence of recurrent, necrotic extremity wounds with mold growth in culture, and/or histopathologic fungal evidence. Non-IFI controls were matched on injury pattern and severity. In a supplemental matching analysis, non-IFI controls were also matched by blood volume transfused within 24 hours of injury. INTERVENTION: None. MAIN OUTCOME MEASUREMENTS: Amputation revision rate and loss of functional levels. RESULTS: Seventy-one IFI cases (112 fungal-infected extremity wounds) were identified and matched to 160 control patients (315 non-IFI extremity wounds). The IFI wounds resulted in significantly more changes in amputation level (P < 0.001). Additionally, significantly (P < 0.001) higher number of operative procedures and longer duration to initial wound closure were associated with IFI. A shorter duration to initial wound closure was significantly associated with wounds lacking IFIs (Hazard ratio: 1.53; 95% confidence interval, 1.17-2.01). The supplemental matching analysis found similar results. CONCLUSIONS: Our analysis indicates that IFIs adversely impact wound healing and patient recovery, requiring more frequent proximal amputation revisions and leading to higher early complication rates. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence. PMID- 26360543 TI - Controlled Synthesis of High-Quality Monolayered alpha-In2Se3 via Physical Vapor Deposition. AB - In this work, we have demonstrated the synthesis of high-quality monolayered alpha-In2Se3 using physical vapor deposition method under atmospheric pressure. The quality of the In2Se3 atomic layers has been confirmed by complementary characterization technologies such as Raman/photoluminescence spectroscopies and atomic force microscope. The atomically resolved images have been obtained by the annular dark-field scanning transmission electron microscope. The field-effect transistors have been fabricated using the atomically layered In2Se3 and exhibit p-type semiconducting behaviors with the mobility up to 2.5 cm(2)/ Vs. The In2Se3 layers also show a good photoresponsivity of 340A/W, as well as 6 ms response time for the rise and 12 ms for the fall. These results make In2Se3 atomic layers a promising candidate for the optoelectronic and photosensitive device applications. PMID- 26360544 TI - The Alarming Increase of Diabetes in Bermuda. PMID- 26360545 TI - Does Computerized Cognitive Behavioral Therapy Help People with Inflammatory Bowel Disease? A Randomized Controlled Trial. AB - BACKGROUND: Cognitive behavioral therapy may be useful for improving health related quality of life (HRQOL) of at least some patients with inflammatory bowel disease (IBD), especially those with psychiatric comorbidities. However, cognitive behavioral therapy can be difficult to access. These difficulties can be overcome by computerized cognitive behavioral therapy (CCBT). This is a randomized controlled trial of a self-administered CCBT intervention for patients with IBD focused on improving HRQOL. It is hypothesized that CCBT completers will have an improved HRQOL relative to people not allocated to CCBT. METHODS: Patients with IBD were randomly allocated to CCBT (n = 113) versus treatment as usual (n = 86). The IBD Questionnaire at 12 weeks after baseline was the primary outcome, while generic HRQOL, anxiety, depression, coping strategies, perceived stress, and IBD symptoms were secondary outcomes. Outcomes were also measured at 6 months after baseline. Predictors of dropout were also determined. RESULTS: Twenty-nine CCBT participants (25.7%) completed the CCBT. The IBD Questionnaire was significantly increased at 12 weeks in CCBT completers compared with treatment-as-usual patients (F = 6.38, P = 0.01). Short Form-12 mental score (F = 5.00, P = 0.03) was also significantly better in CCBT compared with treatment-as usual patients at 12 weeks. These outcomes were not maintained at 6 months. The predictors of dropout were baseline depression, biological use, lower IBD Questionnaire scores, and not having steroids. CONCLUSIONS: Improvements at 12 weeks after baseline were not maintained at 6 months. Future research should aim to improve adherence rates. Moreover, CCBT may not work for patients with IBD with comorbid depression. PMID- 26360546 TI - Metabotropic Glutamate Receptor 2 Positive Allosteric Modulators: Closing the Gate on Drug Abuse? PMID- 26360547 TI - Mu Opioid Receptor Genetic Variation and Heroin Addiction. PMID- 26360548 TI - Efficacy of cytarabine, aclarubicin and granulocyte colony-stimulating factor (CAG) regimen compared to FLAG regimen for adult patients with relapsed/refractory Philadelphia chromosome-negative acute lymphoblastic leukemia. AB - In this study, we retrospectively assess the results in comparing the efficacies and toxicities of the three chemotherapy regimens: CAG (cytarabine, aclarubicin and granulocyte colony-stimulating factor (G-CSF), n=87), HD-CAG (increasing the dose of aclarubicin in CAG regimen, n=73), and FLAG (fludarabine, cytarabine and G-CSF, n=41) regimens in patients with relapsed/refractory Philadelphia chromosome-negative acute lymphoblastic leukemia (Ph--ALL). Our study indicated that after one therapy course, the overall response (OR, complete reimssion (CR)+partial remission (PR)) rate was higher in CAG than that in FLAG regimen (55.2% vs. 31.7%, P=0.013), while the CR (50.7% vs. 26.8%, P =0.013) and OR (64.4% vs. 31.7%, P=0.001) rates in HD-CAG regimen were both higher than that in FLAG regimen. Furthermore, the results were more pronounced in the subgroup of patients with T cell and refractory Ph--ALL. There were no significant differences in CR and OR rates between the CAG and HD-CAG regimens. Meanwhile, the adverse effects of CAG regimen were less toxic than the FLAG and HD-CAG regimens. There were no statistically significant differences in overall survival rates at two years among the three groups (FLAG: 9.8%+/-4.6%, CAG: 11.8%+/-4.5%, HD-CAG: 11.1%+/-4.0%; P>0.05). Our preliminary results indicated that CAG and HD CAG regimens could be more effective and safer than FLAG regimen for relapsed/refractory Ph--ALL. PMID- 26360550 TI - Walter Riss, PhD, 1925-2015. PMID- 26360549 TI - Mutational analysis of telomere complex genes in Indian population with acquired aplastic anemia. AB - BACKGROUND: Acquired aplastic anemia (AAA) is rare disorders caused due to the profound or almost complete bone marrow failure. It is a life threatening hematopoietic stem cells disorder, which is characterized by pancytopenia or complete loss of blood-forming cells. The aim of the present study is to screen for the mutations in telomerase complex genes, and to establish a molecular and hematological profile of Indian sub population. METHODOLOGY: We have conducted a case control study of total 70 participants; 50 patients, who fulfilled the blood count and bone marrow criteria of the International agranulocytosis & AAA, and 20 healthy controls. These samples were selected from hematology clinics at Jaipur, India, during the period of two years (January 2012-December 2013). We screened four telomere complex genes; TERT, DKC1, NOP10 and NHP2 of mutations at single base pair in sampled blood and bone marrows. We have predicated the consequences of mutations on protein structure using 3D multilevel modeling protein structure software Phyre2, PolyPhen2 and YASARA. RESULTS: The hematological and molecular basis of acquired aplastic anemia was investigated in 50 anemia patients and 20 healthy controls. AAA patients showed hematologic abnormalities (macrocytic anemia, thrombocytopenia, & granulocytopenia) in peripheral blood and severe hypoplastic bone marrows. Screening of telomere complex genes TERT, DKC1, NOP10 and NHP2 in AAA patients and controls revealed; novel and reported mutations in TERT and DKC1, whereas, no pathogenic mutations were observed in NOP10 and NHP2 genes. In TERT gene, one non-synonymous mutation (Chr5: 1287,825 C->T; Arg979Trp) was identified in exon 12 and two heterozygous non-synonymous mutations (Chr X: 153,994,542 T->K; Val105Gly & Chr X: 153,994,591 T->K; Ser121Arg) were found in exon 5 of DKC1 gene. To determine and visualize the possible effect of TERT and DKC1 mutations on protein structure YASARA with FoldX functionality has been used and many structural consequences were found that might destabilize the protein. Predicated structural consequences may destabilize the TERT and DKC1 proteins ultimately causing blood disorders.. CONCLUSION: The present study indicates the mutation spectrum in the genes implicated in AAA, i.e. TERT, DKC1, NOP10 and NHP2 on small case-control group in an Indian sub population. PMID- 26360552 TI - Effect of the structure on luminescent characteristics of SRO-based light emitting capacitors. AB - In this paper, we study the structural, optical and electro-optical properties of silicon rich oxide (SRO) films, with 6.2 (SRO30) and 7.3 at.% (SRO20) of silicon excess thermally annealed at different temperatures and used as an active layer in light emitting capacitors (LECs). A typical photoluminescence (PL) red-shift is observed as the silicon content and annealing temperature are increased. Nevertheless, when SRO30 films are used in LECs, a resistance switching (RS) behavior from a high current state (HCS) to a low conduction state (LCS) is observed, enhancing the intense blue electroluminescence (EL). This RS produces a long spectral blue-shift (~227 nm) between the EL and PL band, and it is related to structural defects created by a high current flow through preferential conductive paths breaking off Si-Si bonds from very small silicon nanoparticles (Si-nps) (Edelta (Si ? Si = Si) centers). LECs with SRO20 films do not present the RS behavior and only exhibit a slight shift between PL and EL, both in red spectra. The carrier transport in these LEC devices is analyzed as being trap assisted tunnelling and Poole-Frenkel through a quasi 'continuum' of defect traps and quantum dots for the conduction mechanism in SRO30 and SRO20 films, respectively. The results prove the feasibility of obtaining light emitting devices by using simple panel structures with Si-nps embedded in the dielectric layer. PMID- 26360551 TI - Cancer-Testis Antigen Expression in Serous Endometrial Cancer with Loss of X Chromosome Inactivation. AB - BACKGROUND: Cancer-testis antigens (CTAs) are potential targets for cancer immunotherapy. Many CTAs are located on the X chromosome and are epigenetically regulated. Loss of X chromosome inactivation (XCI) is observed in breast and ovarian cancers and is thought to be related to the overexpression of CTAs. We investigated the relation between expression of CTAs and loss of XCI in endometrial cancer. MATERIALS AND METHODS: We used data generated by The Cancer Genome Atlas Genome Data Analysis Centers and data for Xist knockout mice available at the Gene Expression Omnibus. RESULTS: The status of XCI was estimated by methylation status, and deletion or gain of the X chromosome. The endometrial cancers were classified into the following three groups: preserved inactivated X chromosome (Xi) (n = 281), partial reactivation of Xi (n = 52), and two copies of active X group (n = 38). Loss of XCI was more common in serous adenocarcinoma. Expression of CTAs increased in endometrial cancer with loss of XCI, which was accompanied by global hypomethylation. Expression of CTAs did not increase in Xist knockout mice. CONCLUSIONS: Loss of XCI is common in serous adenocarcinoma. Global hypomethylation, and not loss of XCI, is the main mechanism of overexpression of CTAs. PMID- 26360554 TI - What we talk about when we talk about risk. PMID- 26360553 TI - Molecular changes associated with chronic liver damage and neoplastic lesions in a murine model of hereditary tyrosinemia type 1. AB - Hereditary tyrosinemia type 1 (HT1) is the most severe inherited metabolic disease of the tyrosine catabolic pathway, with a progressive hepatic and renal injury and a fatal outcome if untreated. Toxic metabolites accumulating in HT1 have been shown to elicit endoplasmic reticulum (ER) stress response, and to induce chromosomal instability, cell cycle arrest and apoptosis perturbation. Although many studies have concentrated on elucidating these events, the molecular pathways responsible for development of hepatocellular carcinoma (HCC) still remain unclear. In this study the fah knockout murine model (fah(-/-)) was used to investigate the cellular signaling implicated in the pathogenesis of HT1. Fah(-/-) mice were subjected to drug therapy discontinuation (Nitisinone withdrawal), and livers were analyzed at different stages of the disease. Monitoring of mice revealed an increasing degeneration of the overall physiological conditions following drug withdrawal. Histological analysis unveiled diffuse hepatocellular damage, steatosis, oval-like cells proliferation and development of liver cell adenomas. Immunoblotting results revealed a progressive and chronic activation of stress pathways related to cell survival and proliferation, including several stress regulators such as Nrf2, eIF2alpha, CHOP, HO-1, and some members of the MAPK signaling cascade. Impairment of stress defensive mechanisms was also shown by microarray analysis in fah(-/-) mice following prolonged therapy interruption. These results suggest that a sustained activation of stress pathways in the chronic HT1 progression might play a central role in exacerbating liver degeneration. PMID- 26360555 TI - Treating the cause, not the symptoms, of mental illness stigma. PMID- 26360556 TI - Understanding risk of homicide among mental health patients. PMID- 26360557 TI - Balancing care for patients at risk of death by suicide. PMID- 26360558 TI - Suicide risk in adults with Asperger's syndrome. PMID- 26360559 TI - Implications of the Francis Inquiry for mental health research. PMID- 26360560 TI - Attacks on antidepressants: signs of deep-seated stigma? PMID- 26360561 TI - Why I think antidepressants cause more harm than good. PMID- 26360562 TI - Mental health services provision in Somaliland. PMID- 26360563 TI - Corrections. PMID- 26360564 TI - Active engagement for people bereaved by suicide. PMID- 26360565 TI - Mental health in Portugal in times of austerity. PMID- 26360566 TI - Psychosis susceptibility syndrome: an alternative name for schizophrenia. PMID- 26360567 TI - Psychosis susceptibility syndrome: an alternative name for schizophrenia. PMID- 26360569 TI - Management of autism in France: "a huge job to be done". PMID- 26360570 TI - The songs that saved your life. PMID- 26360571 TI - Karl Friston: resisting the philosopause. PMID- 26360572 TI - School daze. PMID- 26360573 TI - Leading questions. PMID- 26360574 TI - The recovery position. PMID- 26360575 TI - Effect of the Time to Change anti-stigma campaign on trends in mental-illness related public stigma among the English population in 2003-13: an analysis of survey data. AB - BACKGROUND: Understanding trends and effective mechanisms that are likely to reduce public stigma and discrimination towards people with mental illness is important. We aimed to assess changes in public stigma in England after the introduction of the Time to Change anti-stigma campaign. METHODS: We used data from the 2003 and 2007-13 national Attitudes to Mental Illness surveys to investigate 10-year trends in public attitudes across England before and during the Time to Change anti-stigma campaign. We present annual mean scores for attitude items related to prejudice and exclusion, and tolerance and support for community care. We also present an extrapolated linear trend line for the years 2009-13 and estimate population attitude scores without the campaign. We present unadjusted and adjusted linear regression models. In addition, we used multivariable linear regression models fitted to data aggregated by region to investigate whether a dose-effect response exists between campaign awareness and regional outcomes related to knowledge, attitudes, and intended behaviour. FINDINGS: About 1700 respondents were surveyed each year. Significant increases in positive attitudes related to prejudice and exclusion occurred after the Time to Change campaign. In the multivariable analysis, we noted a significant increase in positive attitudes in relation to prejudice and exclusion after the launch of Time to Change (reverse-coded Z score 0.02, 95% CI 0.01 to 0.05; p=0.01), but not for tolerance and support for community care (Z score 0.01, 0.01 to 0.03; p=0.27). We also found evidence for a dose-effect relation between campaign awareness and regional improvement in knowledge (p=0.004) and attitudes (tolerance and support p<0.0001; prejudice and exclusion p=0.001), but not intended behaviour (p=0.20). INTERPRETATION: The positive effects of Time to Change seem to be significant and moderate. Although attitudes are probably more at risk of deterioration during times of economic hardship, anti-stigma programmes might still play an active part in long-term reduction of stigma and discrimination, especially in relation to prejudice and exclusion of people with mental health problems. FUNDING: UK Department of Health, Comic Relief, Big Lottery. PMID- 26360576 TI - Patients with mental illness as victims of homicide: a national consecutive case series. AB - BACKGROUND: The media attention received by homicides committed by patients with mental illness is thought to increase stigma. However, people with mental illness can also be victims of violence. We aimed to assess how often victims of homicide are current mental health patients and their relationship to the perpetrators. METHODS: In a national consecutive case-series study, we obtained data for victims and perpetrators of all confirmed homicides between Jan 1, 2003, and Dec 31, 2005, in England and Wales. We requested information about contact with mental health services in the 12 months before the homicide for all victims and perpetrators. For victims and perpetrators who had contact with mental health services in the 12 months before homicide, we sent questionnaires to the clinician responsible for the patient's care. FINDINGS: 1496 victims of confirmed homicide died between Jan 1, 2003, and Dec 31, 2005, in England and Wales. Patients with mental illness were more likely to die by homicide than were people in the general population (incidence rate ratio 2.6, 95% CI 1.9-3.4). 90 homicide victims (6%) had contact with mental health services in the 12 months before their death. 213 patients with mental illness were convicted of homicide in the same 3 year period. 29 of 90 patient victims were killed by another patient with mental illness. In 23 of these 29 cases, the victim and perpetrator were known to each other, and in 21 of these cases, the victims and perpetrators were undergoing treatment at the same National Health Service Trust. In these 29 cases in which patient victims were killed by another patient with mental illness, alcohol and drug misuse (19 victims [66%], 27 perpetrators [93%]) and previous violence (7 victims [24%], 7 perpetrators [24%]) were common in both victims and, particularly, perpetrators. In seven of the 29 cases in which the victim was killed by another patient with mental illness, both victim and perpetrator were diagnosed with schizophrenia. INTERPRETATION: The high risk of patients with mental illness being victims of homicide is an important antistigma message, although this risk partly comes from other patients with mental illness; overall, the risk of patients committing homicide is greater than the risk of being a victim of homicide. Identification and safeguarding of patients at risk of violence should be prominent in clinical risk assessment. FUNDING: Healthcare Quality Improvement Partnership. PMID- 26360577 TI - Safety of patients under the care of crisis resolution home treatment services in England: a retrospective analysis of suicide trends from 2003 to 2011. AB - BACKGROUND: Community care provided by crisis resolution home treatment teams is used increasingly as an alternative to admission to psychiatric wards. No systematic analysis has been done of the safety of these teams in terms of rates of suicide. We aimed to compare the rate and number of suicides among patients under the care of crisis resolution home treatment teams with those of psychiatric inpatients. We also assessed the clinical features of individuals who died by suicide in both home and hospital settings. METHODS: We did a retrospective longitudinal analysis between 2003 and 2011 of all adults (aged 18 years or older) treated by the National Health Service in England who died by suicide while under the care of crisis resolution home treatment services or as a psychiatric inpatient. We obtained data from the National Confidential Inquiry into Suicide and Homicide by People with Mental Illness and from the Mental Health Minimum Dataset. FINDINGS: 1256 deaths by suicide (12% of all patient suicides) were recorded among patients cared for under crisis resolution home treatment teams, an average of 140 deaths per year. Different denominators meant that direct comparison between groups was difficult, but the average rate of suicide under crisis resolution home treatment services (14.6 per 10 000 episodes under crisis care) seemed higher than the average rate of suicide among psychiatric inpatients (8.8 per 10 000 admissions). The number of suicides in patients under the care of crisis resolution home treatment teams increased from an average of 80 per year (in 2003 and 2004) to 163 per year (in 2010 and 2011) and were twice as frequent as inpatient suicides in the last few years of the study. However, because of the growing number of patients under the care of crisis resolution home treatment teams, the average rate of suicide fell by 18% between the first and last 2 years of the study. 548 (44%) patients who died by suicide under the care of crisis resolution home treatment teams lived alone and 594 (49%) had had a recent adverse life event. In a third of patients (n=428) under the care of crisis resolution home treatment teams, suicide happened within 3 months of discharge from psychiatric inpatient care. INTERPRETATION: Although the number of suicides under the care of crisis resolution home treatment teams has risen since 2003, the rate has fallen. However, suicide rates remain high compared with the inpatient setting, and safety of individuals cared for by crisis resolution home treatment teams should be a priority for mental health services. For some vulnerable people who live alone or have adverse life circumstances, crisis resolution home treatment might not be the most appropriate care setting. Use of crisis resolution home treatment teams to facilitate early discharge could present a risk to some patients, which should be investigated further. FUNDING: Healthcare Quality Improvement Partnership. PMID- 26360578 TI - Suicidal ideation and suicide plans or attempts in adults with Asperger's syndrome attending a specialist diagnostic clinic: a clinical cohort study. AB - BACKGROUND: Asperger's syndrome in adulthood is frequently associated with depression, but few studies have explored the lifetime experience of self reported suicidal ideation and suicide plans or attempts in this clinical group. We aimed to assess this prevalence in a clinical cohort of patients in the UK. METHOD: In a clinical cohort study, we undertook a retrospective analysis of clinical survey data from adults newly diagnosed with Asperger's syndrome at a specialist diagnostic clinic between Jan 23, 2004, and July 8, 2013, in England. Patients completed a self-report questionnaire before clinical assessment, recording lifetime experience of depression, suicidal ideation, and suicide plans or attempts, along with self-reported measures of autistic traits and empathy. We compared the rate of suicidal ideation in the sample with published rates of suicidal ideation in the general population and other clinical groups. We also assessed associations between depression, autistic traits, empathy, and likelihood of suicidal ideation and suicide plans or attempts. FINDINGS: 374 adults (256 men and 118 women) were diagnosed with Asperger's syndrome in the study period. 243 (66%) of 367 respondents self-reported suicidal ideation, 127 (35%) of 365 respondents self-reported plans or attempts at suicide, and 116 (31%) of 368 respondents self-reported depression. Adults with Asperger's syndrome were significantly more likely to report lifetime experience of suicidal ideation than were individuals from a general UK population sample (odds ratio 9.6 [95% CI 7.6-11.9], p<0.0001), people with one, two, or more medical illnesses (p<0.0001), or people with psychotic illness (p=0.019). Compared with people diagnosed with Asperger's syndrome without depression, people with Asperger's syndrome and depression were more likely to report suicidal ideation (p<0.0001) and suicide plans or attempts (p<0.0001). INTERPRETATION: Our findings lend support to anecdotal reports of increased rates of suicidal ideation in adults with Asperger's syndrome, and depression as an important potential risk factor for suicidality in adults with this condition. Because adults with Asperger's syndrome often have many risk factors for secondary depression (eg, social isolation or exclusion, and unemployment), our findings emphasise the need for appropriate service planning and support to reduce risk in this clinical group. FUNDING: The Three Guineas Trust, the Baily Thomas Foundation, the Medical Research Council, NIHR-CLAHRC-EoE, Cambridgeshire and Peterborough NHS Foundation Trust (CPFT), and the Autism Research Trust. PMID- 26360579 TI - Computational psychiatry: the brain as a phantastic organ. AB - In this Review, we discuss advances in computational neuroscience that relate to psychiatry. We review computational psychiatry in terms of the ambitions of investigators, emerging domains of application, and future work. Our focus is on theoretical formulations of brain function that put subjective beliefs and behaviour within formal (computational) frameworks-frameworks that can be grounded in neurophysiology down to the level of synaptic mechanisms. Understanding the principles that underlie the brain's functional architecture might be essential for an informed phenotyping of psychopathology in terms of its pathophysiological underpinnings. We focus on active (Bayesian) inference and predictive coding. Specifically, we show how basic principles of neuronal computation can be used to explain psychopathology, ranging from impoverished theory of mind in autism to abnormalities of smooth pursuit eye movements in schizophrenia. PMID- 26360580 TI - Depression, pregnancy, and HIV: the case to strengthen mental health services for pregnant and post-partum women in sub-Saharan Africa. PMID- 26360581 TI - The Lancet Psychiatry: the whole equation. PMID- 26360582 TI - Copy Number Gains at 8q24 and 20q11-q13 in Gastric Cancer Are More Common in Intestinal-Type than Diffuse-Type. AB - The present study was aimed at discovering DNA copy number alterations (CNAs) involved in the carcinogenesis of stomach and at understanding their clinicopathological significances in the Korean population. DNA copy numbers were analyzed using Agilent 244K or 400K array comparative genomic hybridization (aCGH) in fresh-frozen tumor and matched normal tissues from 40 gastric cancer patients. Some of the detected CNA regions were validated using multiplex ligation-dependent probe amplification (MLPA) in six of the 40 patients and customized Agilent 60K aCGH in an independent set of 48 gastric cancers. The mRNA levels of genes at common CNA regions were analyzed using quantitative real-time PCR. Copy number gains were more common than losses across the entire genome in tumor tissues compared to matched normal tissues. The mean number of alterations per case was 64 for gains and 40 for losses, and the median aberration length was 44016 bp for gains and 4732 bp for losses. Copy number gains were frequently detected at 7p22.1 (20%), 8q24.21 (27%-30%), 8q24.3 (22%-48%), 13q34 (20%-31%), and 20q11-q13 (25%-30%), and losses at 3p14.2 (43%), 4q35.2 (27%), 6q26 (23%), and 17p13.3 (20%-23%). CNAs at 7p22.1, 13q34, and 17p13.3 have not been reported in other populations. Most of the copy number losses were associated with down regulation of mRNA levels, but the correlation between copy number gains and mRNA expression levels varied in a gene-dependent manner. In addition, copy number gains tended to occur more commonly in intestinal-type cancers than in diffuse type cancers. In conclusion, the present study suggests that copy number gains at 8q24 and 20q11-q13 and losses at 3p14.2 may be common events in gastric cancer but CNAs at 7p22.1, 13q34, and 17p13.3 may be Korean-specific. PMID- 26360584 TI - Correction: Identification and Risk Assessment for Worldwide Invasion and Spread of Tuta absoluta with a Focus on Sub-Saharan Africa: Implications for Phytosanitary Measures and Management. PMID- 26360583 TI - Most Trial Eligibility Criteria and Patient Baseline Characteristics Do Not Modify Treatment Effect in Trials Using Targeted Therapies for Rheumatoid Arthritis: A Meta-Epidemiological Study. AB - OBJECTIVE: To determine if variations in trial eligibility criteria and patient baseline characteristics could be considered effect modifiers of the treatment response when testing targeted therapies (biological agents and targeted synthetic disease modifying antirheumatic drugs (DMARDs)) for rheumatoid arthritis (RA). METHODS: We conducted a meta-epidemiological study of all trials evaluating a targeted therapy approved by regulatory authorities for treating RA. The database search was completed on December 11th 2013. Eligible trials reported ACR20 data at months 3-6 and used an add-on design. Odds ratios (ORs) were calculated from the response rates and compared among the trial eligibility criteria/patient baseline characteristics of interest. Comparisons are presented as the Ratio of Odds Ratios (ROR). RESULTS: Sixty-two trials (19,923 RA patients) were included in the primary analyses using ACR20 response. Overall, targeted therapies constituted an effective treatment (OR 3.96 95% confidence interval (CI) 3.41 to 4.60). The majority of the trial eligibility criteria and patient baseline characteristics did not modify treatment effect. The added benefit of targeted therapies was lower in trials including "DMARD-naive" patients compared with trials including "DMARD inadequate responders" (ROR = 0.45, 95%CI 0.31 to 0.66) and trials including "targeted therapy inadequate responders" (0.50, 95%CI 0.29 to 0.87), test for interaction: p = 0.0002. Longer mean disease duration was associated with a higher likelihood of responding to treatment (beta = 1.05, 95%CI 1.00 to 1.11 OR's per year; p = 0.03). Analyses conducted using DAS28 remission as the outcome supported the above-mentioned findings. CONCLUSION: Our results suggest that a highly selective inclusion is not associated with greater treatment effect, as might otherwise be expected. The added benefit of a targeted therapy was lower in trials including patients who were DMARD-naive and trials including patients with shorter disease durations. PMID- 26360585 TI - Non-coding RNAs: Functions and applications in endocrine-related cancer. AB - A significant fraction of the human genome is transcribed as non-coding RNAs (ncRNAs). This non-coding transcriptome has challenged the notion of the central dogma and its involvement in transcriptional and post-transcriptional regulation of gene expression is well established. Interestingly, several ncRNAs are dysregulated in cancer and current non-coding transcriptome research aims to use our increasing knowledge of these ncRNAs for the development of cancer biomarkers and anti-cancer drugs. In endocrine-related cancers, for which survival rates can be relatively low, there is a need for such advancements. In this review, we aimed to summarize the roles and clinical implications of recently discovered ncRNAs, including long ncRNAs, PIWI-interacting RNAs, tRNA- and Y RNA-derived ncRNAs, and small nucleolar RNAs, in endocrine-related cancers affecting both sexes. We focus on recent studies highlighting discoveries in ncRNA biology and expression in cancer, and conclude with a discussion on the challenges and future directions, including clinical application. ncRNAs show great promise as diagnostic tools and therapeutic targets, but further work is necessary to realize the potential of these unconventional transcripts. PMID- 26360586 TI - Pharmacotherapy for the treatment of obesity. AB - The recognition of the complex counter-regulatory hormonal, metabolic and neurochemical mechanisms that promote weight regain following weight loss and the conceptualisation of obesity as a chronic disease requiring long-term management has led to increasing focus on the role of adjunctive therapies for obesity, particularly pharmacotherapy. Currently available pharmacotherapy achieves a weight loss intermediate between that commonly attained by lifestyle intervention and bariatric surgery, however its accessibility, compared to bariatric surgery increases its appeal. Despite the poor history of obesity pharmacotherapy, novel agents that are in development appear to have several advantages over predecessors. They are generally more selective in their mechanism of action, thereby potentially minimising adverse sequelae and improving the risk-benefit ratio of pharmacotherapy. Another approach has been to use combined pharmacotherapy to better counteract the multiple counter-regulatory neuroendocrine mechanisms which promote weight regain, as well as allowing lower constituent doses of the combined monotherapy agents, which improves the safety and tolerability of these agents that are usually required long-term for chronic weight maintenance. This review will provide an overview of past, present and future pharmacotherapy for obesity. The efficacy and safety profile of currently available pharmacotherapy will be discussed in the setting of stringent regulatory review processes now in place given the fraught history of pharmacological interventions for obesity. Potential novel therapies that seek to better target the multiple complex counter-regulatory mechanisms promoting weight regain while improving the efficacy/safety profile, will also be examined. PMID- 26360587 TI - Combination cannabinoid and opioid receptor antagonists improves metabolic outcomes in obese mice. AB - The CB1 receptor antagonist, rimonabant, causes weight loss but also produces undesirable psychiatric side effects. We investigated using a combination of rimonabant with the opioid receptor antagonists naloxone and norBNI to treat the metabolic sequelae of long-term high fat diet feeding in mice. This combination has previously been shown to have positive effects on both weight loss and mood related behaviour. Diet-induced obese mice were treated chronically with either low dose rimonabant (1 mg/kg) or the combination of rimonabant, naloxone and norBNI (rim nal BNI). After 6 days of treatment, glucose and insulin tolerance tests were performed and body composition analysed using DEXA. Changes in BAT thermogenesis were assessed using implantable radio telemetry probes. Behavioural responses to acute rimonabant or rim nal BNI were examined in the forced swim test and elevated plus maze. Separately, we assessed shifts in Fos immunoreactivity in response to rimonabant or rim nal BNI. Rim nal BNI was significantly better than rimonabant treatment alone at reducing body weight and food intake. In addition, it improved fasting blood glucose and fat mass. Acute low dose rimonabant did not alter behaviour in either the forced swim test or elevated plus maze. Combination rim nal BNI reversed the behavioural effects of high dose (10 mg/kg) rimonabant in obese mice. Rim nal BNI altered Rimonabant induced Fos in a number of nuclei, with particular shifts in expression in the central and basolateral amygdala, and insular cortex. This study demonstrates that the combination of rimonabant, naloxone and norBNI is effective at producing weight loss over a sustained period of time without altering performance in standardised mouse behaviour tests. Fos expression patterns offer insight into the neuroanatomical substrates subserving these physiological and behavioural changes. These results indicate that CB1-targeted drugs for weight loss may still be feasible. PMID- 26360588 TI - Real or Artificial? Intergroup Biases in Mind Perception in a Cross-Cultural Perspective. AB - Recent research suggests that attributions of aliveness and mental capacities to faces are influenced by social group membership. In this article, we investigated group related biases in mind perception in participants from a Western and Eastern culture, employing faces of varying ethnic groups. In Experiment 1, Caucasian faces that ranged on a continuum from real to artificial were evaluated by participants in the UK (in-group) and in India (out-group) on animacy, abilities to plan and to feel pain, and having a mind. Human features were found to be assigned to a greater extent to faces when these belonged to in-group members, whereas out-group faces had to appear more realistic in order to be perceived as human. When participants in India evaluated South Asian (in-group) and Caucasian (out-group) faces in Experiment 2, the results closely mirrored those of the first experiment. For both studies, ratings of out-group faces were significantly predicted by participants' levels of ethnocultural empathy. The findings highlight the role of intergroup processes (i.e., in-group favoritism, out-group dehumanization) in the perception of human and mental qualities and point to ethnocultural empathy as an important factor in responses to out-groups. PMID- 26360590 TI - Phenomenology of obsessive compulsive disorder: Taking a fresh look. PMID- 26360589 TI - Control of macrophage metabolism and activation by mTOR and Akt signaling. AB - Macrophages are pleiotropic cells that assume a variety of functions depending on their tissue of residence and tissue state. They maintain homeostasis as well as coordinate responses to stresses such as infection and metabolic challenge. The ability of macrophages to acquire diverse, context-dependent activities requires their activation (or polarization) to distinct functional states. While macrophage activation is well understood at the level of signal transduction and transcriptional regulation, the metabolic underpinnings are poorly understood. Importantly, emerging studies indicate that metabolic shifts play a pivotal role in control of macrophage activation and acquisition of context-dependent effector activities. The signals that drive macrophage activation impinge on metabolic pathways, allowing for coordinate control of macrophage activation and metabolism. Here we discuss how mTOR and Akt, major metabolic regulators and targets of such activation signals, control macrophage metabolism and activation. Dysregulated macrophage activities contribute to many diseases, including infectious, inflammatory, and metabolic diseases and cancer, thus a better understanding of metabolic control of macrophage activation could pave the way to the development of new therapeutic strategies. PMID- 26360591 TI - Application of a validated LC-MS/MS method for JWH-073 and its metabolites in blood and urine in real forensic cases. AB - Synthetic cannabinoids, which were synthesized to improve the therapeutic effects of cannabis, have become a major issue when they are abused. They have different chemical structures from tetrahydrocannabinol (THC) but similar effects on endocannabinoid receptors. "Spice" named products have more serious side effects than cannabis and can even cause death. These mixtures are prepared by spraying chemicals onto small pieces of herbs and are being dishonestly sold as "natural" and "legal" products over the internet. Their popularity is continuously increasing. Studies on detecting synthetic cannabinoids in biological samples as well as pharmacology and toxicology studies of these chemicals are very limited. A fast, specific and robust method for the detection and quantification of JWH 073, JWH-073 N-butanoic acid, and JWH-073 N-(4-hydroxybutyl) in blood and urine has been developed that uses solid-phase extraction (SPE) followed by UPLC-MS/MS analysis. This method has been validated in terms of its linearity (0.1-50 ng/mL), selectivity, intra-assay and inter-assay accuracy and precision (CV<10%), recovery (75-95%), limits of detection (LODs) (0.08-0.13 ng/mL), and limits of quantification (LOQs) (0.11-0.17 ng/mL). Matrix effects, stability, and process efficiency parameters of this method have also been assessed. This method was applied to 2596 authentic samples received by the Department of Toxicology (Istanbul) in the Presidency of Council of Forensic Medicine (Turkey) between September 1, 2012, and February 28, 2015. PMID- 26360592 TI - Methadone-related deaths. A ten year overview. AB - Over the last 10 years we have registered in our district (about 500,000 inhabitants) 36 cases of fatal methadone poisoning, involving both patients on treatment and naive subjects: this is a significant increase of deaths due to methadone use, misuse or abuse compared with previous years. Twenty-four patients (66.7%) were on methadone maintenance programs for heroin detoxification, while 12 (33.3%) were taking the drug without a medical prescription. The average blood concentration of methadone in patients undergoing a maintenance program was 1.06 mg/L (0.21-3.37 mg/L), against 0.79 mg/L (0.2-3.15 mg/L) in those taking the non prescribed drug. Since 111 heroin-related deaths were recorded in our district in the same period, the fact that there appear to be many methadone deaths (about a third of heroin-related deaths) cannot be overlooked. The aim of this work is to understand the possible reasons for such a large number of methadone-related deaths. On this subject, we have noticed that risks associated with methadone intake are often underestimated by clinicians prescribing the drug: sometimes methadone is prescribed without taking into account patient's tolerance to opiates, and a large number of subjects enrolled in methadone maintenance programs in Italy, have also been given take-home doses, thus increasing the risk of abuse and diversion. PMID- 26360593 TI - Silk fibroin as biomaterial for bone tissue engineering. AB - Silk fibroin (SF) is a fibrous protein which is produced mainly by silkworms and spiders. Its unique mechanical properties, tunable biodegradation rate and the ability to support the differentiation of mesenchymal stem cells along the osteogenic lineage, have made SF a favorable scaffold material for bone tissue engineering. SF can be processed into various scaffold forms, combined synergistically with other biomaterials to form composites and chemically modified, which provides an impressive toolbox and allows SF scaffolds to be tailored to specific applications. This review discusses and summarizes recent advancements in processing SF, focusing on different fabrication and functionalization methods and their application to grow bone tissue in vitro and in vivo. Potential areas for future research, current challenges, uncertainties and gaps in knowledge are highlighted. STATEMENT OF SIGNIFICANCE: Silk fibroin is a natural biomaterial with remarkable biomedical and mechanical properties which make it favorable for a broad range of bone tissue engineering applications. It can be processed into different scaffold forms, combined synergistically with other biomaterials to form composites and chemically modified which provides a unique toolbox and allows silk fibroin scaffolds to be tailored to specific applications. This review discusses and summarizes recent advancements in processing silk fibroin, focusing on different fabrication and functionalization methods and their application to grow bone tissue in vitro and in vivo. Potential areas for future research, current challenges, uncertainties and gaps in knowledge are highlighted. PMID- 26360594 TI - Nanostructured hydroxyapatite surfaces-mediated adsorption alters recognition of BMP receptor IA and bioactivity of bone morphogenetic protein-2. AB - Highly efficient loading of bone morphogenetic protein-2 (BMP-2) onto carriers with desirable performance is still a major challenge in the field of bone regeneration. Till now, the nanoscaled surface-induced changes of the structure and bioactivity of BMP-2 remains poorly understood. Here, the effect of nanoscaled surface on the adsorption and bioactivity of BMP-2 was investigated with a series of hydroxyapatite surfaces (HAPs): HAP crystal-coated surface (HAP), HAP crystal-coated polished surface (HAP-Pol), and sintered HAP crystal coated surface (HAP-Sin). The adsorption dynamics of recombinant human BMP-2 (rhBMP-2) and the accessibility of the binding epitopes of adsorbed rhBMP-2 for BMP receptors (BMPRs) were examined by a quartz crystal microbalance with dissipation. Moreover, the bioactivity of adsorbed rhBMP-2 and the BMP-induced Smad signaling were investigated with C2C12 model cells. A noticeably high mass uptake of rhBMP-2 and enhanced recognition of BMPR-IA to adsorbed rhBMP-2 were found on the HAP-Pol surface. For the rhBMP-2-adsorbed HAPs, both ALP activity and Smad signaling increased in the order of HAP-Sin90% ee), which are versatile chiral (18)F synthons for the synthesis of radiotracers. The utility of this process is demonstrated with the synthesis of the PET (positron emission tomography) tracer (2S,4S)-4-[(18)F]fluoroglutamic acid. PMID- 26360632 TI - Cancer and serious mental illness--patient, caregiver and professional perspectives: study protocol. AB - AIM: To explore the experience of serious mental illness and cancer from the perspective of patients, significant others and healthcare professionals involved in their care. BACKGROUND: Serious mental illness is associated with poorer cancer outcomes. Those suffering from this comorbidity receive fewer specialist interventions and die earlier than the general population. Prior qualitative research in this area has comprised of a single study focussing on healthcare professionals and there is little evidence regarding the experiences of patients and caregivers. DESIGN: A qualitative exploration using approximately 36 semi structured interviews. METHODS: Semi-structured digitally recorded interviews conducted with: adults living with serious mental illness and diagnosed with cancer; those providing them with informal support and care; and healthcare professionals. Questions will focus on the experience of having cancer and serious mental illness or caring for someone with this comorbidity, experiences of healthcare and priorities for patients and carers. Framework analysis will be used. Research Ethics Committee and Trust Research & Development approval was obtained. A steering group comprising six people with experience of either cancer or mental illness provided feedback and ratified the patient information sheets and interview schedules. DISCUSSION: There is a paucity of research addressing stakeholder perspectives on the experience of cancer and of cancer services for people with serious mental illness. Dissemination of findings will inform practice relating to the care of an often neglected population, informing better support for their significant others and the professionals involved in their care. PMID- 26360633 TI - CACTA-superfamily transposable element is inserted in MYB transcription factor gene of soybean line producing variegated seeds. AB - The R gene of soybean, presumably encoding a MYB transcription factor, controls seed coat color. The gene consists of multiple alleles, R (black), r-m (black spots and (or) concentric streaks on brown seed), and r (brown seed). This study was conducted to determine the structure of the MYB transcription factor gene in a near-isogenic line (NIL) having r-m allele. PCR amplification of a fragment of the candidate gene Glyma.09G235100 generated a fragment of about 1 kb in the soybean cultivar Clark, whereas a fragment of about 14 kb in addition to fragments of 1 and 1.4 kb were produced in L72-2040, a Clark 63 NIL with the r-m allele. Clark 63 is a NIL of Clark with the rxp and Rps1 alleles. A DNA fragment of 13 060 bp was inserted in the intron of Glyma.09G235100 in L72-2040. The fragment had the CACTA motif at both ends, imperfect terminal inverted repeats (TIR), inverse repetition of short sequence motifs close to the 5' and 3' ends, and a duplication of three nucleotides at the site of integration, indicating that it belongs to a CACTA-superfamily transposable element. We designated the element as Tgm11. Overall nucleotide sequence, motifs of TIR, and subterminal repeats were similar to those of Tgm1 and Tgs1, suggesting that these elements comprise a family. PMID- 26360634 TI - Synthesis of Naamidine A and Selective Access to N(2)-Acyl-2-aminoimidazole Analogues. AB - A short and scalable synthesis of naamidine A, a marine alkaloid with a selective ability to inhibit epidermal growth factor receptor (EGFR)-dependent cellular proliferation, has been achieved. A key achievement in this synthesis was the development of a regioselective hydroamination of a monoprotected propargylguanidine to deliver N(3)-protected cyclic ene-guanidines. This permits the extension of this methodology to prepare N(2)-acyl analogues in a fashion that obviates the troublesome acylation of the free 2-aminoimidazoles, which typically yields mixtures of N(2)- and N(2),N(2)-diacylated products. PMID- 26360635 TI - More realistic power estimation for new user, active comparator studies: an empirical example. AB - PURPOSE: Pharmacoepidemiologic studies are often expected to be sufficiently powered to study rare outcomes, but there is sequential loss of power with implementation of study design options minimizing bias. We illustrate this using a study comparing pancreatic cancer incidence after initiating dipeptidyl peptidase-4 inhibitors (DPP-4i) versus thiazolidinediones or sulfonylureas. METHODS: We identified Medicare beneficiaries with at least one claim of DPP-4i or comparators during 2007-2009 and then applied the following steps: (i) exclude prevalent users, (ii) require a second prescription of same drug, (iii) exclude prevalent cancers, (iv) exclude patients age <66 years and (v) censor for treatment changes during follow-up. Power to detect hazard ratios (effect measure strongly driven by the number of events) >= 2.0 estimated after step 5 was compared with the naive power estimated prior to step 1. RESULTS: There were 19,388 and 28,846 DPP-4i and thiazolidinedione initiators during 2007-2009. The number of drug initiators dropped most after requiring a second prescription, outcomes dropped most after excluding patients with prevalent cancer and person time dropped most after requiring a second prescription and as-treated censoring. The naive power (>99%) was considerably higher than the power obtained after the final step (~75%). CONCLUSIONS: In designing new-user active-comparator studies, one should be mindful how steps minimizing bias affect sample-size, number of outcomes and person-time. While actual numbers will depend on specific settings, application of generic losses in percentages will improve estimates of power compared with the naive approach mostly ignoring steps taken to increase validity. PMID- 26360637 TI - Response to 'In Response to "Intravenous Lipid Emulsion Given to Volunteers does not Affect Symptoms of Lidocaine Brain Toxicity"'. PMID- 26360636 TI - Investigation of the HIV-1 matrix interactome during virus replication. AB - PURPOSE: Like all viruses, human immunodeficiency virus type 1 (HIV-1) requires host cellular factors for productive replication. Identification of these factors may lead to the development of novel cell-based inhibitors. EXPERIMENTAL DESIGN: A Strep-tag was inserted into the C-terminus of the matrix (MA) region of the HIV 1 gag gene. The resultant virus was replication competent and used to infect Jurkat T-cells. MA complexes were affinity purified with Strep-Tactin agarose. Protein quantification was performed using sequential window acquisition of all theoretical fragment ion spectra (SWATH) MS, data were log2 -transformed, and Student t-tests with Bonferroni correction used to determine statistical significance. Several candidate proteins were validated by immunoblot and investigated for their role in virus infection by siRNA knockdown assays. RESULTS: A total of 17 proteins were found to be statistically different between the infected versus uninfected and untagged control samples. X-ray repair cross complementing protein 6 (Ku70), X-ray repair cross-complementing protein 5 (Ku80), and Y-box binding protein 1 (YB-1) were confirmed to interact with MA by immunoblot. Knockdown of two candidates, EZRIN and Y-box binding protein 1, enhanced HIV infection in vitro. CONCLUSIONS AND CLINICAL RELEVANCE: The Strep tag allowed for the capture of viral protein complexes in the context of virus replication. Several previously described factors were identified and at least two candidate proteins were found to play a role in HIV-1 infection. These data further increase our understanding of HIV host -cell interactions. PMID- 26360638 TI - Design of a low-density SNP chip for the main Australian sheep breeds and its effect on imputation and genomic prediction accuracy. AB - Genotyping sheep for genome-wide SNPs at lower density and imputing to a higher density would enable cost-effective implementation of genomic selection, provided imputation was accurate enough. Here, we describe the design of a low-density (12k) SNP chip and evaluate the accuracy of imputation from the 12k SNP genotypes to 50k SNP genotypes in the major Australian sheep breeds. In addition, the impact of imperfect imputation on genomic predictions was evaluated by comparing the accuracy of genomic predictions for 15 novel meat traits including carcass and meat quality and omega fatty acid traits in sheep, from 12k SNP genotypes, imputed 50k SNP genotypes and real 50k SNP genotypes. The 12k chip design included 12 223 SNPs with a high minor allele frequency that were selected with intermarker spacing of 50-475 kb. SNPs for parentage and horned or polled tests also were represented. Chromosome ends were enriched with SNPs to reduce edge effects on imputation. The imputation performance of the 12k SNP chip was evaluated using 50k SNP genotypes of 4642 animals from six breeds in three different scenarios: (1) within breed, (2) single breed from multibreed reference and (3) multibreed from a single-breed reference. The highest imputation accuracies were found with scenario 2, whereas scenario 3 was the worst, as expected. Using scenario 2, the average imputation accuracy in Border Leicester, Polled Dorset, Merino, White Suffolk and crosses was 0.95, 0.95, 0.92, 0.91 and 0.93 respectively. Imputation scenario 2 was used to impute 50k genotypes for 10 396 animals with novel meat trait phenotypes to compare genomic prediction accuracy using genomic best linear unbiased prediction (GBLUP) with real and imputed 50k genotypes. The weighted mean imputation accuracy achieved was 0.92. The average accuracy of genomic estimated breeding values (GEBVs) based on only 12k data was 0.08 across traits and breeds, but accuracies varied widely. The mean GBLUP accuracies with imputed 50k data more than doubled to 0.21. Accuracies of genomic prediction were very similar for imputed and real 50k genotypes. There was no apparent impact on accuracy of GEBVs as a result of using imputed rather than real 50k genotypes, provided imputation accuracy was >90%. PMID- 26360639 TI - Relationship between computerized wheeze detection and lung function parameters in young infants. AB - OBJECTIVE: Computerized respiratory sound analysis (CORSA) has been validated in the assessment of wheeze in infants, but it is unknown whether automatically detected wheeze is associated with impaired lung function. This study investigated the relationship between wheeze detection and conventional lung function testing (LFT) parameters. METHODS: CORSA was performed using the PulmoTrack(r) monitor in 110 infants, of median (interquartile range) postmenstrual age 50 (46-56) weeks and median body weight 4,810 (3,980-5,900) g, recovering from neonatal intensive care. In the same session, LFT was performed, including tidal breathing measurements, occlusion tests, body plethysmography, forced expiratory flow by rapid thoracoabdominal compression, sulfur hexafluoride (SF6 ) multiple breath washout (MBW), and capillary blood gas analysis. Infants were classified as wheezers or non-wheezers using predefined cut-off values for the duration of inspiratory and expiratory wheeze. RESULTS: Wheezing was detected in 72 (65%) infants, with 43 (39%) having inspiratory and 53 (48%) having expiratory wheezing. Endotracheal mechanical ventilation in the neonatal period for > 24 hr was associated with inspiratory wheeze (P = 0.009). Airway resistance was increased in both inspiratory (P = 0.02) and expiratory (P = 0.004) wheezers and correlated with the duration of expiratory wheeze (r = 0.394, P < 0.001). Expiratory wheezers showed a significant increase in respiratory resistance (P = 0.001), time constant (0.012), and functional residual capacity using SF6 MBW (P = 0.019). There was no association between wheezing and forced expiratory flow or blood gases. CONCLUSION: CORSA can help identify neonates and young infants with subclinical airway obstruction and may prove useful in the follow-up of high-risk infants. PMID- 26360640 TI - Provocation tests for the diagnosis of food-dependent exercise-induced anaphylaxis. AB - BACKGROUND: Little has been reported regarding provocation tests for the diagnosis of food-dependent exercise-induced anaphylaxis (FDEIA), especially in children and adolescents. Hence, we here aimed to examine the usefulness and safety of such tests for FDEIA. METHODS: We retrospectively analyzed 41 patients with 184 provocation tests. The patients underwent ergometer stress tests after ingesting the suspected foods along with aspirin. When one or more allergic symptoms appeared, we judged the provocation test as positive. RESULTS: Based on 30 positive test results (16%), we diagnosed 20 patients (49%) as FDEIA. The major causative foods were as follows: wheat alone (five patients), combination of wheat and shrimp (three patients), combination of wheat and apple (two patients), and peach alone (two patients). The symptoms appeared within 45 min after initiating exercise in 29 tests (97%). The most frequent symptoms were cutaneous symptoms, which appeared in 25 tests (83%). Of the 30 positive tests, 6 (20%) required administration of adrenaline. After discharge, the patients with negative test results had no episodes of FDEIA due to the suspected foods that they had been tested for. CONCLUSION: Provocation tests enabled us to confirm the diagnosis of FDEIA when positive and to exclude the diagnosis when negative. However, as severe symptoms may appear, these tests should be performed in a hospital under constant supervision of a physician. PMID- 26360641 TI - An efficient S-NO-polysilsesquioxane nano-platform for the co-delivery of nitric oxide and an anticancer drug. AB - Codelivery of nitric oxide (NO) and drugs based on a single nanocarrier is a promising therapeutic strategy. Here, we report a one-step nanoprecipitation method to generate nanoparticles that possess simultaneous NO-donating and doxorubicin releasing properties. S-Nitroso polysilsesquioxane acts like an avid "drug sponge" that attracts drug molecules into nanospheres. PMID- 26360643 TI - Protein Flexibility in Docking-Based Virtual Screening: Discovery of Novel Lymphoid-Specific Tyrosine Phosphatase Inhibitors Using Multiple Crystal Structures. AB - Incorporating protein flexibility is a major challenge for docking-based virtual screening. With an increasing number of available crystal structures, ensemble docking with multiple protein structures is an efficient approach to deal with protein flexibility. Herein, we report the successful application of a docking based virtual screen using multiple crystal structures to discover novel inhibitors of lymphoid-specific tyrosine phosphatase (LYP), a potential drug target for autoimmune diseases. The appropriate use of multiple protein structures allowed a better enrichment than a single structure in the recovery of known inhibitors. Subsequently, an optimal ensemble of LYP structures was selected and used in docking-based virtual screening. Eight novel LYP inhibitors (IC50 ranging from 7.95 to 56.6 MUM) were identified among 23 hit compounds. Further studies demonstrated that the most active compound B15 possessed some selectivity over other protein phosphatases and could effectively up-regulate TCR (T cell receptor)-mediated signaling in Jurkat T cells. These novel hits not only provided good starting points for the development of therapeutic agents useful in autoimmune diseases but also demonstrated the advantages of choosing an appropriate ensemble of protein structures in docking-based virtual screening over using a single protein conformation. PMID- 26360642 TI - Involvement of Lipocalin-like CghA in Decalin-Forming Stereoselective Intramolecular [4+2] Cycloaddition. AB - Understanding enzymatic Diels-Alder (DA) reactions that can form complex natural product scaffolds is of considerable interest. Sch 210972 1, a potential anti-HIV fungal natural product, contains a decalin core that is proposed to form through a DA reaction. We identified the gene cluster responsible for the biosynthesis of 1 and heterologously reconstituted the biosynthetic pathway in Aspergillus nidulans to characterize the enzymes involved. Most notably, deletion of cghA resulted in a loss of stereoselective decalin core formation, yielding both an endo (1) and a diastereomeric exo adduct of the proposed DA reaction. Complementation with cghA restored the sole formation of 1. Density functional theory computation of the proposed DA reaction provided a plausible explanation of the observed pattern of product formation. Based on our study, we propose that lipocalin-like CghA is responsible for the stereoselective intramolecular [4+2] cycloaddition that forms the decalin core of 1. PMID- 26360644 TI - Changes in nuclear receptor corepressor RIP140 do not influence mitochondrial content in the cortex. AB - Changes in nuclear receptor interacting protein 140 (RIP140) influences mitochondrial content in skeletal muscle; however, the translation of these findings to the brain has not been investigated. The present study examined the impact of overexpressing and ablating RIP140 on mitochondrial content in muscle and the cortex through examining mRNA, mtDNA, and mitochondrial protein content. Our results show that changes in RIP140 expression significantly alters markers of mitochondrial content in skeletal muscle but not the brain. PMID- 26360645 TI - Immediate video feedback on ramp, wheelie, and curb wheelchair skill training for persons with spinal cord injury. AB - We hypothesized that the effects of immediate video feedback (IVF) on training ramp, wheelie, and curb wheelchair skills for persons with spinal cord injury (SCI) would be equivalent to or better than the traditional wheelchair skill training. Participants were manual wheelchair users with recent SCI (thoracic 1 lumbar 1) who were matched (9 pairs) on motor function level, age, and sex and randomly assigned to a control group (conventional training) or an experimental group (IVF training). Participants learned three wheelchair skills and then went through the wheelchair skill competency test, retention test, and transfer test. Paired t-tests were used to examine the differences in training time (minutes), spotter intervention needed (counts), and successful rate in performance between the two groups. A 2 (groups) x 3 (skills) x 3 (tests) repeated-measures analysis of variance and Bonferroni adjustment test were used to examine differences between groups on wheelchair skills and tests. No differences were found between two groups in training times (minutes) on three wheelchair skills (experimental vs control: ramp 14.92 +/- 5.80 vs 11.69 +/- 7.85; wheelie 17.79 +/- 6.03 vs 19.92 +/- 13.42; and curb 38.35 +/-23.01 vs 48.59 +/- 15.21). This study demonstrated that IVF for training manual wheelchair skills may produce similar results as the conventional training and may be an alternative training method for wheelchair skills. PMID- 26360646 TI - Mechanisms of Vasorelaxation Induced by Hexahydrocurcuminin Isolated Rat Thoracic Aorta. AB - This study was designed to examine the vasorelaxant effects of hexahydrocurcumin (HHC), one of the major natural metabolites of curcumin from Curcuma longa, on rat isolated aortic rings, and the underlying mechanisms. Isometric tension of the aortic rings was recorded using organ bath system. HHC (1 nM to 1 mM) relaxed the endothelium-intact aortic rings pre-contracted with PE and KCl in a concentration-dependent manner. Removal of the endothelium did not alter the effect of HHC-induced relaxation. In Ca(2+)-free Krebs solution, HHC significantly inhibited the CaCl2-induced contraction in high K(+) depolarized rings and suppressed the transient contraction induced by PE and caffeine in a concentration-dependent manner. HHC was also observed to relax phobal-12 myristate-13-acetate (PMA), an activator of protein kinase C (PKC), precontracted aortic rings in a concentration-dependent manner with EC50 values equivalent to 93.36 +/- 1.03 MUM. In addition, pre-incubation with propranolol (a beta adrenergic receptor blocker) significantly attenuated the HHC-induced vasorelaxation. These results suggest that the vasorelaxant effect of HHC is mediated by the endothelium-independent pathway, probably because of the inhibition of extracellular Ca(2+) influx through voltage-operated Ca(2+) channels and receptor-operated Ca(2+) channels, the inhibition of Ca(2+) mobilization from intracellular stores, as well as inhibition of PKC-mediated Ca(2+)-independent contraction. Moreover, HHC produces vasorelaxant effects probably by stimulating the beta-adrenergic receptor. PMID- 26360647 TI - Induction of Canonical Wnt Signaling by the Alarmins S100A8/A9 in Murine Knee Joints: Implications for Osteoarthritis. AB - OBJECTIVE: Both alarmins S100A8/A9 and canonical Wnt signaling have been found to play active roles in the development of experimental osteoarthritis (OA). However, what activates canonical Wnt signaling remains unknown. This study was undertaken to investigate whether S100A8 induces canonical Wnt signaling and whether S100 proteins exert their effects via activation of Wnt signaling. METHODS: Expression of the genes for S100A8/A9 and Wnt signaling pathway members was measured in an experimental OA model. Selected Wnt signaling pathway members were overexpressed, and levels of S100A8/A9 were measured. Activation of canonical Wnt signaling was determined after injection of S100A8 into naive joints and induction of collagenase-induced OA in S100A9-deficient mice. Expression of Wnt signaling pathway members was tested in macrophages and fibroblasts after S100A8 stimulation. Canonical Wnt signaling was inhibited in vivo to determine if the effects of S100A8 injections were dependent on Wnt signaling. RESULTS: The alarmins S100A8/A9 and members of the Wnt signaling pathway showed coinciding expression in synovial tissue in an experimental OA model. Synovial overexpression of selected Wnt signaling pathway members did not result in increased expression of S100 proteins. In contrast, intraarticular injection of S100A8 increased canonical Wnt signaling, whereas canonical Wnt signaling was decreased after induction of experimental OA in S100A9-deficient mice. S100A8 stimulation of macrophages, but not fibroblasts, resulted in increased expression of canonical Wnt signaling members. Overexpression of Dkk-1 to inhibit canonical Wnt signaling decreased the induction of matrix metalloproteinase 3, interleukin-6, and macrophage inflammatory protein 1alpha after injection of S100A8. CONCLUSION: Our findings indicate that the alarmin S100A8 induces canonical Wnt signaling in macrophages and murine knee joints. The effects of S100A8 are partially dependent on activation of canonical Wnt signaling. PMID- 26360649 TI - Nanopore Diameters Tune Strain in Extruded Fibronectin Fibers. AB - Fibronectin is present in the extracellular matrix and can be assembled into nanofibers in vivo by undergoing conformational changes. Here, we present a novel approach to prepare fibronectin nanofibers under physiological conditions using an extrusion approach through nanoporous aluminum oxide membranes. This one-step process can prepare nanofiber bundles up to a millimeter in length and with uniform fiber diameters in the nanometer range. Most importantly, by using different pore diameters and protein concentrations in the extrusion process, we could induce varying lasting structural changes in the fibers, which were monitored by Forster resonance energy transfer and should impose different physiological functions. PMID- 26360648 TI - Sustained attention training reduces spatial bias in Parkinson's disease: a pilot case series. AB - Individuals with Parkinson's disease (PD) commonly demonstrate lateralized spatial biases, which affect daily functioning. Those with PD with initial motor symptoms on the left body side (LPD) have reduced leftward attention, whereas PD with initial motor symptoms on the right side (RPD) may display reduced rightward attention. We investigated whether a sustained attention training program could help reduce these spatial biases. Four non-demented individuals with PD (2 LPD, 2 RPD) performed a visual search task before and after 1 month of computer training. Before training, all participants showed a significant spatial bias and after training, all participants' spatial bias was eliminated. PMID- 26360650 TI - Influence of Cdp-Choline Administration on Early Burn Edema in Rats. AB - PURPOSE: The cholinergic anti-inflammatory pathway may play an important role in early burn edema. Therefore, we evaluated the influence of cdp-choline on early systemic burn edema and leukocyte activation in shock in rat mesenteries after burn plasma transfer. METHODS: Burn plasma harvested from donor rats 4 hours after thermal injury (30% total body surface area, 100 degrees C water, 12 seconds) was administered intravenously to healthy animals during 2 hours of intravital microscopy. Shamburn plasma (same procedure but water at 37 degrees C) was transferred for negative controls. In the study group, bolus injection of 100 mg/kg body weight cdp-choline was undertaken 15 minutes before examination. Intravital microscopy was performed in the ileal portion of rat mesenteries at 0, 60, and 120 minutes. Capillary leakage was assessed by fluorescein isothiocyanate albumin extravasation and leukocyte-endothelial interaction were observed via transillumination microscopy. To assure comparable hemodynamic conditions, microhemodynamic parameters, foremost venular wall shear rate, were assessed. RESULTS: Capillary leakage increased significantly after burn plasma transfer when compared to the shamburn group. Additional intravenous administration of cdp choline attenuates macromolecular efflux to shamburn levels. Leukocyte activation is reduced after cdp-choline treatment. CONCLUSIONS: The significant increase of albumin efflux in rat mesenteries after burn plasma transfer is decreased by additional cdp-choline bolus administration. Further investigations for proof of the relevance of the cholinergic anti-inflammatory pathway in early burn trauma are strongly required. PMID- 26360651 TI - Repair of Full-Thickness Nasal Alar Defects Using Nasolabial Perforator Flaps. AB - BACKGROUND: The repair of full-thickness nasal alar defects presents difficulties because of their complex 3-dimensional structure. Reconstructions using inappropriate methods may lead to asymmetries and dissatisfying functional results. In this study, our aim was to present the repairs of full-thickness alar defects performed using cartilage-supported nasolabial perforator flaps. MATERIALS AND METHODS: Eight patients who presented to our clinic between January 2011 and April 2014 with full-thickness defects in the alar wings were included in this study. The nasolabial perforator flap was prepared on the basis of the closest perforator to the defect area and in a way to include 2 to 3 mm of subcutaneous adipose tissue. The medial section of the flap was adapted to form the nasal lining. In the 7 patients in whom cartilage support was used, the cartilage graft was obtained from the septum nasi. After the cartilage was placed on the flap, the lateral section of the flap was folded over the medial section and the defect was repaired. In 1 patient in whom cartilage support was not required, the flap was folded over itself before the repair was performed. The flap donor area was primarily repaired. RESULTS: No detachment around the suture lines, infection, venous insufficiency in the flap, or partial or total flap losses were observed in any of the patients. Retraction developed in 1 patient in whom no cartilage support was used. No retraction was observed in any of the patients in whom cartilage support was used. The results were functionally and esthetically satisfying in all the patients. CONCLUSIONS: The greatest advantage of perforator-based nasolabial flaps is the greater mobilization achieved in comparison with the other nasolabial flaps. Thus, full-thickness defects can be repaired in 1 session in some patients, no revision is required around the flap pedicle, and much less donor area morbidity occurs. Nasal alar reconstructions performed using this type of flap lead to both esthetically and functionally satisfying results. PMID- 26360652 TI - Origin, Reality, and Clinical Importance of the Arcade of Struthers: An Anatomic Study. AB - The literature contains confusing and opposing views about the naming, prevalence, anatomic structure, and clinical significance of the arcade of Struthers. The conflicting rates of arcade (between 0% and 100%) prevalence found in the literature may be due to the varying definition of the arcade among the authors, as well as the dissection method. The present study aims to examine the structure to determine whether or not the arcade of Struthers exists through an anatomic dissection study of a fresh human cadaver and seeks to compare its findings with those in the literature. Twenty arms from fresh frozen cadavers were dissected. An arcade of Struthers was not found in any specimen. Study concluded that its existence is unproven, and the arcade of Struthers does not exist. PMID- 26360653 TI - Preoperative Albumin Alone is Not a Predictor of 30-Day Outcomes in Pressure Ulcer Patients: A Matched Propensity-Score Analysis of the 2006-2011 NSQIP Datasets. AB - BACKGROUND: While there has been a great deal of literature describing the relationship between nutritional status and development of pressure ulcers, statistically rigorous studies analyzing the relationship between hypoalbuminemia and outcomes are lacking. METHODS: The American College of Surgeons' multicenter, prospective, National Surgical Quality Improvement Program database was used to identify patients who underwent surgery for treatment of pressure ulcers between 2006 and 2011. Matched propensity-score analysis was performed to match experimental groups with regard to preoperative comorbidities. Outcomes of interest included overall/surgical/medical complications and 30-day mortality. Multivariable logistic regression models were used to assess the independent association between hypoalbuminemia and outcomes. RESULTS: Over the 6-year study period, 551 patients met criteria for study inclusion. Median albumin level was 2.8 g/dL. Before propensity matching, multiple adverse outcomes were significantly elevated in patients with albumin levels below the median value (very-low albumin, or VLA), compared to control patients. However, after matching preoperative comorbidities, the differences in 30-day outcomes were eliminated. In both analyses, there was no significant difference in 30-day surgical complications. CONCLUSIONS: It is generally understood that hypoalbuminemic patients have elevated risks for surgical procedures. In pressure ulcer patients, it appears that these risks are not due to hypoalbuminemia alone, but rather a long list of attendant comorbidities. Consequently, hypoalbuminemia alone should not be used to determine the timing of a procedure for pressure ulcer surgery. Knowledge of these risks is necessary for patient counseling and surgical planning in this population. PMID- 26360654 TI - The Effect of Activated Protein C on Attenuation of Ischemia-Reperfusion Injury in a Rat Muscle Flap Model. AB - Ischemia-reperfusion injury is often the final and irreversible factor causing flap failure in microsurgery. The salvage of a microsurgical flap with an ischemia-reperfusion injury contributes to the success of microsurgical flap transfers. Activated protein C (APC), a serine protease with anticoagulant and anti-inflammatory activities, has been shown to improve ischemic flap survival. To date, APC has yet to be applied to models of free flap with ischemia reperfusion injury. In this study, we aimed to investigate the effect of APC on gracilis flap ischemia-reperfusion injury induced by gracilis vessels clamping and reopening. Sixty male Sprague-Dawley rats were randomly divided into 2 groups. After 4 hours of clamping for ischemia, flaps were reperfused and recombinant human APC (25 MUg/kg) or saline was injected in the flaps through pedicles. At 0, 1, 4, 18, and 24 hours after injection (n = 6 for each time point), the tissue samples were harvested. The muscle viability at 24 hours in saline group was 54.8% (15.1%), whereas the APC-treated group was 90.0% (4.3%) (P < 0.05). The induced nitric oxide synthase (iNOS) mRNA expression increased with the time after reperfusion, which were 0.93 (0.25) to 2.09 (0.22) in saline group, and 0.197 (0.15) to 0.711 (0.15) in the APC-treated group. iNOS mRNA expression in the APC-treated group was significantly higher than the saline group at 1, 18, and 24 hours (P < 0.05). Numerous inflammatory cells were observed infiltrating and invading the muscle fibers in the saline group more than the APC-treated group. Increased number of polymorphonuclear cells was also noted in the saline group compared with the APC-treated group (P < 0.05). In conclusion, APC treatment can significantly attenuate ischemia-reperfusion injury and increase the survival of the free flap through down-regulating iNOS mRNA expression and reducing the inflammatory cells. Further research is still needed to be done on various mechanisms in which APC is protective to prevent tissue damage. PMID- 26360655 TI - The Oncologic Safety of Breast Fat Grafting and Contradictions Between Basic Science and Clinical Studies: A Systematic Review of the Recent Literature. AB - Fat grafting is increasingly popular and is becoming a common practice in plastic surgery for postmastectomy breast reconstruction and aesthetic breast augmentation; however, concerns over the oncologic safety remains a controversial and hot topic among scientists and surgeons. Basic science and laboratory research repeatedly show a potentially dangerous effect of adipose-derived stem cells on breast cancer cells; however, clinical research, although limited, continually fails to show an increase in breast cancer recurrence after breast fat grafting, with the exception of 1 small study on a subset patient population with intraepithelial neoplasm of the breast. The aim of this review is to summarize the recent conflicting basic science and clinical data to better understand the safety of breast fat grafting from an oncological perspective. PMID- 26360656 TI - Reconstruction of Desmoid Tumors: Case Series and Systematic Review. AB - BACKGROUND: Desmoid tumors (DT) represent a group of rare, distinct lesions. There are few published studies examining outcomes and safety of complex reconstruction after DT resection. METHODS: A retrospective review identified 39 patients who underwent surgical treatment of DT at St. Jude Children's Research Hospital over a 12-year period. A systematic review of the literature identified 17 further studies for inclusion. Treatment characteristics were analyzed. RESULT: Thirty-nine patients were treated during the study period, with a total number of 67 resections. Median age was 12.2 years; 49% of patients were male, and 51% were female. Median tumor size was 9.8 cm. DT most commonly arose in the extremities (40%), thorax (23%), head and neck (21%), and trunk (16%). One- and 5 year recurrence-free survival were 97.1% and 73.1%, respectively. The majority of defects were closed primarily, with the exception of head and neck defects. Long term outcomes were good for chest, abdomen, and upper extremity defects, but were problematic for head and neck, breast, and lower extremity defects. There were no recurrences at the site of flap harvest in either the study population or in reviewed studies. CONCLUSION: For patients with DT, surgical extirpation should not come at the expense of functional preservation, as overall survival is excellent. However, specific defects, including those of the lower extremity, breast, and head and neck, will benefit from improved techniques for resection and reconstruction. PMID- 26360657 TI - The Discrete Scar in Prominent Ear Correction: A Digital 3-Dimensional Analysis to Determine the Ideal Incision for Otoplasty: Reply. PMID- 26360658 TI - Polyethylene Glycol- or Sodium Picosulphate-Based Laxatives Before Colonoscopy in Children. AB - OBJECTIVES: The purpose of this randomised study was to compare the quality of bowel cleansing using either polyethylene glycol (PEG) or sodium picosulphate (NaPico) (primary outcome) in relation to the tolerability and acceptance of these laxatives among children and their caregivers (secondary outcome). METHODS: The study was a randomised controlled trial that was conducted as an investigator blinded study within the Department of Paediatrics of Skane University Hospital in Malmo, Sweden. A total of 72 children (10-18 years of age) were randomly placed into 1 of 2 groups (PEG or NaPico). The Ottawa Bowel Preparation Quality Score was used to evaluate the quality of bowel cleansing. A total of 2 different questionnaires were used to evaluate both the acceptability and tolerability of the laxatives. RESULTS: In total, 71 children completed the bowel cleansing. Of these 71 cleanses, 67 protocols were analysed according to the Ottawa Bowel Preparation Quality Score. No significant difference in bowel cleansing quality was detected between the 2 groups. Rates of acceptability and tolerability were significantly higher in the NaPico group than in the PEG group. CONCLUSIONS: In the present study, both laxatives were found to be satisfactory in terms of aiding the performance of an uncomplicated and successful colonoscopy. NaPico was, however, more tolerable to the children than PEG, and both, the children and their caregivers, were more accepting of NaPico than of PEG. Consequently, NaPico can be recommended as the option for bowel cleansing in children ages 10 years and older. PMID- 26360659 TI - Inflammatory Fibroid Polyp of the Esophagogastric Junction. PMID- 26360660 TI - Bowel Cleansing Before Colonoscopy in Children: Is This the Beginning of a New Era? PMID- 26360661 TI - The Wall of Pain: Not All Abdominal Pain Is Visceral. PMID- 26360662 TI - Naphthodithiophene-Based Conjugated Polymer with Linear, Planar Backbone Conformation and Strong Intermolecular Packing for Efficient Organic Solar Cells. AB - Two donor-acceptor copolymers, PBDT and PNDT, containing 4,8-bis(2 ethylhexyloxy)benzo[1,2-b:3,4-b']dithiophene (BDT) and 4,9-bis(2 ethylhexyloxy)naphtho[1,2-b:5,6-b']dithiophene (NDT), respectively, as an electron-rich unit and 5,6-difluoro-2,1,3-benzothiadiazole (2FBT) as an electron deficient unit, were synthesized and compared. The introduction of the NDT core into the conjugated backbone was found to effectively improve both light harvesting and the charge carrier mobility by enhancing chain planarity and backbone linearity; the NDT copolymer has stronger noncovalent interactions and smaller bond angles than those of the BDT-based polymer. Moreover, the introduction of the NDT core brings about a drastic change in the molecular orientation into the face-on motif and results in polymer:PCBM blend films with well-mixed interpenetrating nanofibrillar bulk-heterojunction networks with small scale phase separation, which produce solar cells with higher short-circuit current density and fill factor values. A conventional optimized device structure containing PNDT:PC71BM was found to exhibit a maximum solar efficiency of 6.35%, an open-circuit voltage of 0.84 V, a short-circuit current density of 11.92 mA cm(-2), and a fill factor of 63.5% with thermal annealing, which demonstrates that the NDT and DT2FBT moieties are a promising electron-donor/acceptor combination for high-performance photovoltaics. PMID- 26360664 TI - Syrian refugees: health services support and hospitality in Turkey. PMID- 26360663 TI - Booster dose after 10 years is recommended following 17DD-YF primary vaccination. AB - A single vaccination of Yellow Fever vaccines is believed to confer life-long protection. In this study, results of vaccinees who received a single dose of 17DD-YF immunization followed over 10 y challenge this premise. YF-neutralizing antibodies, subsets of memory T and B cells as well as cytokine-producing lymphocytes were evaluated in groups of adults before (NVday0) and after (PVday30 45, PVyear1-4, PVyear5-9, PVyear10-11, PVyear12-13) 17DD-YF primary vaccination. YF-neutralizing antibodies decrease significantly from PVyear1-4 to PVyear12-13 as compared to PVday30-45, and the seropositivity rates (PRNT>=2.9Log10mIU/mL) become critical (lower than 90%) beyond PVyear5-9. YF-specific memory phenotypes (effector T-cells and classical B-cells) significantly increase at PVday30-45 as compared to naive baseline. Moreover, these phenotypes tend to decrease at PVyear10-11 as compared to PVday30-45. Decreasing levels of TNF-alpha(+) and IFN gamma(+) produced by CD4(+) and CD8(+) T-cells along with increasing levels of IL 10(+)CD4(+)T-cells were characteristic of anti-YF response over time. Systems biology profiling represented by hierarchic networks revealed that while the naive baseline is characterized by independent micro-nets, primary vaccinees displayed an imbricate network with essential role of central and effector CD8(+) memory T-cell responses. Any putative limitations of this cross-sectional study will certainly be answered by the ongoing longitudinal population-based investigation. Overall, our data support the current Brazilian national immunization policy guidelines that recommend one booster dose 10 y after primary 17DD-YF vaccination. PMID- 26360665 TI - New Immunosuppressive Cell Therapy to Prolong Survival of Induced Pluripotent Stem Cell-Derived Allografts. AB - BACKGROUND: Induced pluripotent stem cell (iPSC) technology provides new opportunities in regenerative medicine to generate grafts from donors for transplantation. However, particularly when allogeneic iPSCs are used, immune suppression is required to avoid rejection of iPSC-derived grafts. In this study, we examine a concept that protection of iPSCs-derived allografts can be achieved when transplantation is accompanied with the administration of immunosuppressive cells generated from the same iPSCs resource. METHODS: Mouse iPSCs were differentiated into immunosuppressive cells by a culture protocol using granulocyte macrophage-colony-stimulating factor, macrophage-colony-stimulating factor, IL-4, and lipopolysaccharide. Adherent clusters were collected and examined for the ability to suppress allogeneic T- and B-cell responses, as well as for the contribution to prolonged allogeneic graft survival in transplantation models. RESULTS: Myeloid cells with immunosuppressive features were successfully induced from iPSCs, and thus referred to as iPSC-derived suppressor cells (iPS SCs). The iPS-SCs resemble macrophages in terms of cell surface molecules and gene expressions. Furthermore, iPS-SCs efficiently suppressed allogeneic T- and B cell proliferation in a nitric oxide-dependent manner, and iPS-SCs were found to suppress alloantibody production and prolong substantially the survival of iPSC derived grafts, such as embryoid bodies and cardiomyocytes, in in vivo allogeneic transplantation models. CONCLUSIONS: A certain fraction of macrophage-like cells with immunosuppressive functions can be generated from donor iPSCs, which contribute to the prolonged survival of grafts derived from the same iPSCs in allogeneic recipients. These results suggest a new immunosuppressive strategy of combined donor iPSC-derived graft and immunosuppressive cell transplantation in regenerative medicine using iPSCs. PMID- 26360666 TI - Reappraisal of the Role of Portacaval Shunting in the Growth of Patients With Glycogen Storage Disease Type I in the Era of Liver Transplantation. AB - BACKGROUND: Instead of dietary modification, surgical management is considered for correcting growth retardation, poor metabolic control, and hepatocellular adenoma (HCA) in glycogen storage disease (GSD) type I. METHODS: The records of 55 GSD type I patients were retrospectively reviewed. Thirty-two patients underwent only dietary management (group D) and 23 underwent surgical management (group S). In group S, 17 underwent portacaval shunting (PCS), 13 underwent liver transplantation (LT; 7 underwent both PCS and LT). Height-for-age and body mass index-for-age Z-scores based on World Health Organization data were used to compare growth patterns before and after surgery. Changes in metabolic abnormalities and HCA after operation were also investigated. RESULTS: Height-for age Z-scores for group S were higher by an average of 0.377 compared to that for group D. Metabolic abnormalities often disappeared after LT but improved partially after PCS. De novo HCA was detected in 4 patients (13%) from group D, 12 (100%) who underwent PCS, and none who underwent LT. One case of hepatocellular carcinoma and one of hemorrhage from a HCA were noted in group D. Two cases of hepatocellular carcinoma, 2 of hemorrhage, and 1 of necrosis were noted after PCS. CONCLUSIONS: Surgery yielded greater growth improvement than dietary management. However, after PCS, metabolic abnormalities remained unresolved, and the de novo HCA rate was high. Portacaval shunting can be used to improve growth in GSD type I patients when LT is not possible, but close observation for metabolic abnormalities and HCA is essential. PMID- 26360667 TI - Translation of the Outcome Questionnaire-45 (OQ) into Japanese: A cultural adaptation. AB - OBJECTIVE: While there are several Japanese, qualitative, case studies examining psychotherapy outcome, there is a growing need for quantitative psychotherapy outcome research in Japan. This study adapted the Outcome Questionnaire-45 (OQ), one of the most common quantitative measures of clinical outcome, for use in Japan. METHOD: With the help of 6 translators and 116 native Japanese pilot respondents, the original OQ was translated into Japanese following Beaton et al.'s methodology and includes forward translation, synthesis, back translation, and expert committee meetings. RESULTS: The study produced four pre-final versions, two pretest version, and one pilot version of the Japanese OQ. With permission from the original questionnaire developers, a few items were modified to achieve cultural equivalence. The rigorous translation and adaptation processes, evaluated through the Translation Validity Index and Content Validity Index provided semantic, content, and conceptual equivalence between the English and Japanese versions. CONCLUSIONS: The current study partially validated the translation equivalence and cultural adaptation of the Japanese OQ. Study limitations and suggestions for further development are discussed. PMID- 26360668 TI - Association and interaction analysis of excess weight and chronic kidney disease for cardiovascular autonomic neuropathy in the general Chinese population. AB - BACKGROUND: The purpose of this study was to evaluate the associations of excess weight (EW) and/or chronic kidney disease (CKD) with cardiovascular autonomic neuropathy (CAN), and to detect the extent to which interaction of EW and CKD has on the outcome in a Chinese sample. METHOD: We conducted a large-scale, population-based study to analyze the association and interaction of the two factors on CAN in a sample of 2092 Chinese people. Multiple linear regression analysis to include the two main factors and its interaction were employed to detect these relationships. Relative excess risk due to interaction (RERI), the proportion attributable to interaction (AP) and the synergy index (S) were used to estimate the effect of interaction on an additive scale can. RESULT: Multivariable logistic regression (MLR) indicated that body mass index (BMI) was independently associated with CAN (p = 0.006). In addition, a significant positive interaction between BMI and CKD on CAN was estimated (p = 0.042, RETI = 0.473, 95% CI: 0.0615-0.884, AP = 0.203, 95% CI: -0.055 to 0.461 and S = 1.550, 95% CI: 0.667-2.589). CONCLUSION: Our findings suggest that BMI is independently associated with CAN and offer evidence to support the hypothesis that excess weight and CKD have significant positive interactions on CAN. PMID- 26360669 TI - Constipation: opioid antagonists in people prescribed opioids. AB - INTRODUCTION: Constipation is a common adverse effect of opioids. As an example, constipation is reported in 52% of people with advanced malignancy, and this figure rises to 87% in people who are terminally ill and taking opioids. There is no reason to believe that people with chronic non-malignant disease who are prescribed opioids will be any less troubled by this adverse effect. METHODS AND OUTCOMES: We conducted a systematic overview and aimed to answer the following clinical question: What are the effects of opioid antagonists for constipation in people prescribed opioids? The population we studied included people with any condition, although most studies were in people with cancer pain. We searched Medline, Embase, The Cochrane Library, and other important databases up to May 2014 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). RESULTS: At this update, searching of electronic databases retrieved 162 studies. After deduplication and removal of conference abstracts, 84 records were screened for inclusion in the review. Appraisal of titles and abstracts led to the exclusion of 47 studies and the further review of 37 full publications. Of the 37 full articles evaluated, two systematic reviews and one RCT were included at this update. We performed a GRADE evaluation for three PICO combinations. CONCLUSIONS: In this systematic overview we categorised the efficacy for three interventions based on information relating to the effectiveness of alvimopan, methylnaltrexone, and naloxone. PMID- 26360670 TI - Insulin Control of Blood Glucose and GLUT4 Expression in the Skeletal Muscle of Septic Rats. AB - BACKGROUND: Insulin resistance is common in septic patients. The level at which the serum glucose should be maintained using insulin infusions for optimal utilization by skeletal muscles is not yet established. OBJECTIVE: The objective of the present study was to compare glucose transporter 4 (GLUT4) mRNA and GLUT4 expression and glucose utilization at the recommended glucose levels of 6-8 mmol/L (110-140 mg/dL) and 8-10 mmol/L (140-180 mg/dL) in septic rats. SUBJECTS AND METHODS: This was a prospective randomized study using 44 Sprague-Dawley rats (260-330 g). Rats were anaesthetized with gaseous diethyl ether. Catheters were implanted into the jugular vein and artery. Following a laparotomy, rats in the experimental group (n = 36) were rendered septic by standard caecal ligation and puncture (CLP) and intraperitoneal lipopolysaccharide (LPS) infusion (O111:[B4], 1 mg/kg). Control animals (n = 8) underwent laparotomy, but no caecal ligation or puncture and no LPS injection. Four experimental groups were studied: sham operated control, sepsis treated with fluid maintenance only, sepsis treated with fluid and insulin infusion controlling blood glucose concentration at 6-8 mmol/L and sepsis treated with fluid and insulin infusion controlling blood glucose concentration at 8-10 mmol/L. Hyperinsulinaemic-euglycaemic clamp experiment was done before fluid maintenance and insulin treatment to calculate average glucose infusion rate. RESULTS: All septic rats were markedly hyperglycaemic compared with sham-operated controls two hours after operation. Glucose infusion rate during hyperinsulinaemic-euglycaemic clamp experiment was slower in septic rats, suggesting that they were insulin resistant. At the 12th and 24th hour, skeletal muscle was taken to observe pathological change and analyse the GLUT4 mRNA and GLUT4 levels. There were more inflammatory cells, less GLUT4 mRNA and GLUT4 expression in the skeletal muscles of septic rats. Insulin increased the expression of GLUT4 mRNA and GLUT4 in the skeletal muscle of septic rats. Among all septic rats, the expression of GLUT4 mRNA and GLUT4 was more in the 8-10 mmol/L group. CONCLUSION: Blood glucose concentration of 8-10 mmol/L results in more glucose utilization than 6-8 mmol/L in the skeletal muscle of septic rats during insulin therapy. PMID- 26360671 TI - Study of Different Involutive Changes in Bone Mineral Density Measured in Ward's Triangle and Trabecular Volume Measured in Iliac Crest in Relation to Age. AB - BACKGROUND: The ageing process causes changes in the bone structure, in bone mineral density, and musculoskeletal disorders. AIMS: The purpose of this study is to evaluate and compare involutive changes in bone structure that occur in relation to age in men and women through the study of bone mineral density at the Ward's triangle and trabecular volume. SUBJECTS AND METHODS: In this study, we analysed bone mineral density at Ward's triangle in 70 people (38 men and 32 women) and did a histomorphometric study of trabecular volume at the right iliac crest in 66 samples (42 males and 24 females) obtained from autopsies of court cases, aged between 13 and 83 years. RESULTS: The results show significant correlations between measurements of bone mineral density, trabecular volume values and anthropometric measures of age, gender and body mass index. CONCLUSIONS: This study shows involutional changes that occur in the bone mineral density and Ward's triangle in the bone structure during the process of ageing. In addition, both weight and height have a great influence on bone mineral density and changes in bone that occur; and body mass index is a very important determinant of bone mineral density. PMID- 26360672 TI - A Rare Cause of Haemorrhage in the Upper Gastrointestinal System: Bochdalek Hernia. AB - Diaphragmatic hernia originates from insufficient closure of the pericardioperitoneal canals and pleuroperitoneal membranes. It is seen in one in every 4000 births. The general finding in the newborn period is respiratory difficulty. Mortality is 40-50%. There may be other accompanying organ anomalies. Congenital diaphragmatic hernias diagnosed after the newborn period are known as late-presenting congenital diaphragmatic hernias. This group is seen at a level of 5-20% and poses difficulty in diagnosis. This report describes a case under observation and receiving treatment for gastrointestinal haemorrhage, diagnosed as Bochdalek hernia. PMID- 26360673 TI - Regression of Acanthosis Nigricans with the Addition of Sitagliptin and Pioglitazone. AB - Acanthosis nigricans (AN) is a cutaneous disorder associated with various diseases. There are few documented cases of regression of AN. We discuss a case of a 48-year old diabetic woman with resolution of AN after treatment with sitagliptin and pioglitazone. PMID- 26360674 TI - Parameniscal Cyst - A Rare Cause of Popliteal Artery Compression: Treatment with Ultrasound-guided Decompression. PMID- 26360676 TI - Evaluation of Interleukin-10 Levels in Patients Diagnosed with Chronic Hepatitis. AB - OBJECTIVE: One of the most important factors playing a role in chronic hepatitis B pathogenesis is cytokine release and one of the cytokines with anti inflammatory characteristic is interleukin-10 (IL-10). The aim of the present study is to examine IL-10 levels in patients with chronic hepatitis B. SUBJECTS AND METHODS: Sixty-three patients with chronic hepatitis B disease who had not received any antiviral treatment were included in the study. Serum IL-10 level was investigated by enzyme-linked immunosorbent assay (ELISA) method. In the control group, 25 healthy individuals with mean age similar to the patient population were included. Control and patient groups were compared and data were statistically analysed. RESULTS: Interleukin-10 levels of 25 patients with hepatitis B virus (HBV) DNA levels between 2000 and 20 000 IU/mL were compared with those of 25 subjects in the control group, and the level in the chronic hepatitis B group was statistically significantly higher (p < 0.05). Interleukin 10 levels of 38 patients with HBV DNA > 20 000 IU/mL were statistically significantly higher than those in the control group. When chronic hepatitis B patients were compared among themselves, IL-10 levels increased as HBV DNA levels increased. Also, when IL-10 levels of hepatitis B 'e' antigen (HBeAg) positive patients were compared with those of HBeAg negative patients, the difference was not statistically significant. CONCLUSION: It is believed that decreasing IL-10 levels by various methods would have significant contributions in disease progression and treatment. Moreover, IL-10 level may be an important marker in HBeAg seroconversion and evaluation of treatment response. PMID- 26360675 TI - Impact of L-carnitine and Selenium Treatment on Testicular Apoptosis in Rats Exposed to 2.45 GHz Microwave Energy. AB - OBJECTIVE: It has been suggested that electromagnetic radiation (EMR) by wireless devices (2.45 GHz) induces testicular apoptosis. We investigated if supplemental selenium (Se) and L-carnitine may reduce this adverse effect. MATERIAL: Twelve week old male Wistar albino rats were used in this study. Twenty-four rats were equally divided into four groups which were named as: sham group, EMR-only, EMR+L carnitine (1.5 mg L-carnitine/kg/day) and EMR+Se (1.5 mg Se/kg/-every other day). RESULTS: The level of Bcl-2, Bax, caspase-3 and -8 were compared and a significant difference was found between the sham and EMR-only groups (p < 0.05), and Bcl-2, Bax, caspase-3 and -8 expressions increased in the EMR-only group. The level of Bcl-2, Bax, tumour necrosis factor-alpha (TNF-alpha), caspase-3 and -8 were compared and a significant difference was found between the sham and EMR+L carnitine groups (p < 0.05) and Bcl-2, Bax, TNF-alpha, caspase-3 and -8 expressions increased in the EMR+L-carnitine group. The level of Bcl-2, Bax, TNF alpha, caspase-3 and -8 were compared and a significant difference was found between the sham and EMR+Se groups (p < 0.05) and Bcl-2, Bax, TNF-alpha, caspase 3 and -8 expressions increased in the EMR+Se group. When the expression of caspase-8 was compared, a significant difference was found between the EMR-only and EMR+Se groups (p < 0.05). Caspase-8 expression decreased in EMR+Se group compared with EMR-only group. CONCLUSION: Electromagnetic radiation exposure resulted in testicular apoptosis in rats, mainly by the intrinsic pathways by down-regulated expression of caspase-8. Reduction in the activation of the intrinsic pathway of apoptosis was found higher with selenium administration compared with L-carnitine administration. PMID- 26360677 TI - Use of Percutaneous Sonographically Guided Microwave Ablation Therapy to Treat Inoperable Malignant Liver Tumours. AB - AIMS: Microwave ablation (MWA) is a technique which is used to destroy tumours and soft tissues by using microwave energy to create coagulation and localized tissue necrosis. It is used to treat the tumours which are considered to be inoperable and used to treat those patients who are ineligible for surgery due to some factors. The main objective of this study was to evaluate the use of MWA in the treatment of liver cancer. METHODS: The data were collected from Department of Ultrasound, Harbin Medical University Cancer Hospital. From July 2010 to August 2011, a total of 123 patients with liver tumours was referred to Harbin Medical University Cancer Hospital. One hundred patients were selected for this study and treated with MWA. The study group contained 64 (64%) males and 36 (36%) females with an average age (+/- SD) of 52 (+/- 5.1) years. RESULTS: One month after therapy, complete ablation was obtained in nodules. The complete ablation rate in tumors <= 3 cm and those > 3 cm was 98% and 94%, respectively. Microwave ablation success was higher with nodules <= 3 cm (57/58; 98.3%) in comparison to nodules > 3 cm. CONCLUSION: Sonographically guided percutaneous microwave ablation proved to be safe, fast and effective for treatment of hepatocellular carcinoma. PMID- 26360678 TI - A Study of Patients with "Interface Respiratory Failure" Due to Chronic Obstructive Pulmonary Diseases. AB - OBJECTIVE: To explain a definition of "interface respiratory failure" as arterial blood gas assay with arterial oxygen partial pressure in the range of 60-75 mmHg. SUBJECTS AND METHODS: We compared arterial blood gases (ABGs), resting respiratory drive and its derivatives, mechanics of respiratory muscles, resistance and compliance of the respiratory tract and some important cytokines (interleukin-4 and interferon-gamma) of stable chronic obstructive pulmonary disease (COPD) subgroups (total 50 cases) and control group (25 cases). RESULTS: The patients attaining the "interface respiratory failure" stage developed great changes in respiratory mechanics parameters and inflammatory mediator, which might cause the exacerbation of COPD and the inclination to generate "real respiratory failure" and COPD progression. CONCLUSIONS: The definition of interface respiratory failure is scientific, direct and its width is appropriate. We should intervene appropriately and positively to avoid progression from "interface respiratory failure" to the "real respiratory failure" stage, and this avoidance means a higher survival rate and a lower medical expense. Interventions should focus on oxygen therapy, bronchodilators, improving respiratory compliance, cytokines and anti-infective agents, respectively. PMID- 26360679 TI - Aminoglycoside Resistance in Clinical Isolates of Gram Negative Bacilli at the University Hospital of the West Indies, Jamaica: Comparison of Two Time Periods. AB - OBJECTIVE: Aminoglycosides were introduced into use over 60 years ago. The University Hospital of the West Indies (UHWI), a tertiary care teaching hospital, in Kingston, Jamaica, introduced the use of gentamicin in 1973 and amikacin in 1980. This report examined the susceptibility patterns to these agents in 1547 consecutive isolates of Gram negative bacilli (GNB) encountered between September 1 and November 30, 2011, at UHWI and compares the data with those observed previously in 1981 at the same institution. METHODS: The Vitek 2 (bioMerieux, Durham, NC) was used for isolate identification, minimum inhibitory concentration determination and aminoglycoside susceptibility testing. Quality control was done using American Type Culture Collection standard strains of E coli (ATCC 25922) and Pseudomonas aeruginosa (ATCC 27853). RESULTS: Of the 1547 organisms, 267 had resistance to one or both aminoglycosides. Amikacin resistance increased from 0.6% (1981) to 7.2% [2011] (p < 0.05), while gentamicin resistance increased from 6.7% to 14.8% (p < 0.05) for the corresponding period. The majority of samples with aminoglycoside resistant organisms came from the intensive care unit and surgical inpatients. Urine samples persistently produced the largest amount of gentamicin resistant isolates. CONCLUSIONS: Although there has been a statistically significant rise in aminoglycoside resistance, aminoglycosides continue to remain highly effective against approximately 83% of GNB despite continuous usage at this institution for over three decades. Continued national surveillance, implementation of infection control policies and antibiotic stewardship are all essential in retaining low resistance levels. PMID- 26360680 TI - Correlation of Left Ventricular Diastolic Function and Left Ventricular Geometry in Patients with Obstructive Sleep Apnoea Syndrome. AB - BACKGROUND: The aim of this study is to evaluate the correlation of the left ventricular diastolic function and the left ventricular geometry in patients with obstructive sleep apnoea syndrome (OSAS) by echocardiography. METHODS: The 181 patients diagnosed with OSAS were divided into the normal geometry group (NG), the concentric remodelling group (CR), the eccentric hypertrophy group (EH) and the concentric hypertrophy group (CH). Pearson correlation analysis and multiple linear regression analysis were performed toward the correlation of the left ventricular diastolic function and the left ventricular geometry. RESULTS: The E peak in the EH and CH group was significantly reduced, with significant difference; the E/A, Em, Am and Em/Am was reduced in the order of the CR, EH and CH groups, while E/Em was increased, and the difference was significant. Pearson correlation analysis revealed that the Em/Am showed significant negative correlations with the left ventricular mass index (LVMI) [r = -0.419] and relative wall thickness (RWT) [r = -0.289], while the E/Em was significantly positively correlated with the LVMI (r = 0.638) and RWT [r = 0.328] (p < 0.001). Multiple linear regression analysis revealed that LVMI and RWT had influence on the Em/Am and E/Em (r2 = 0.402, r2 = 0.107, p < 0.001). The left ventricular diastolic dysfunction was the worst in the CH group. CONCLUSIONS: There was correlation between the left ventricular diastolic dysfunction and the changes in cardiac geometry. PMID- 26360681 TI - Effects of General-epidural Anaesthesia on Haemodynamics in Patients with Myasthenia Gravis. AB - OBJECTIVE: The current study aims to explore the effects of general-epidural anaesthesia (GEA) on the perioperative haemodynamics in patients with myasthenia gravis (MG), as well as their extubation time. METHODS: A total of 42 MG patients (Ossermann I-II b types) receiving elective total thymectomy were randomized into GEA (n = 20) and general anaesthesia alone (GA; n = 22) groups. Changes in their mean arterial pressure (MAP) and heart rate (HR) were recorded before anesthesia and at the time of intubation, skin incision, sternotomy and extubation. Dosages of general anaesthetics during time unit and the time of extubation and complete recovery from the ending of the operation were also recorded. RESULTS: After anaesthesia, both groups displayed increased MAPs and HRs, with those in the GA group significantly higher than those in the GEA group (p < 0.05). The total consumption of general anaesthetics in the GA group was markedly higher than that in the GEA group (p < 0.01). CONCLUSION: The GEA group had shorter postoperative extubation and recovery time than the GA group (p < 0.01). General-epidural anaesthesia stabilizes perioperative haemodynamics, reduces the consumption of general anaesthetics and shortens extubation time. It is a feasible and ideal anaesthetic method at present. PMID- 26360682 TI - An Examination of the Effects of Leuprolide Acetate Used in the Treatment of Central Precocious Puberty on Bone Mineral Density and 25-Hydroxy Vitamin D. AB - AIM: Leuprolide acetate is a gonadotropin-releasing hormone (GnRH) analogue frequently used in the treatment of central precocious puberty. Research is currently taking place into its effects on endocrine systems. The aim of this study is to investigate the effect of leuprolide acetate on vitamin D and bone mineral density. METHODS: Twenty-three children diagnosed with central precocious puberty and receiving leuprolide acetate therapy for at least 12 months, and a control group of 17 healthy children were enrolled. In the study group, calcium, phosphorus, alkaline phosphatase, parathormone and 25-hydroxy vitamin D levels and bone mineral density were measured. The results were compared with those of the control group. RESULTS: 25-Hydroxy vitamin D levels in the study and control groups were 15.17 +/- 7 mg/dL and 22.2 +/- 6.1 mg/dL, respectively (p < 0.05). In terms of bone mineral density, osteopenia was determined in 13 (56.5%) patients in the study group and osteoporosis in one (4.3%), while osteopenia was identified in seven patients in the control group, with no osteoporosis being identified (p > 0.05). CONCLUSION: Gonadotropin-releasing hormone agonists may have an adverse effect on bone health. They may exhibit these effects by impacting on vitamin D levels. These levels should be periodically monitored in patients receiving treatment, and vitamin D support should be given in cases where the deficiency is identified. PMID- 26360683 TI - Upper Gastrointestinal Bleeding in Children: The Role of Helicobacter pylori Infection and Non-steroidal Anti-inflammatory Drug Use. AB - OBJECTIVE: To study the role of non-steroidal anti-inflammatory drugs (NSAIDs) and Helicobacter pylori infection in the aetiology of upper gastrointestinal bleeding (UGIB) in children. SUBJECTS AND METHODS: One hundred and eighty-eight patients (82 girls, 106 boys; mean age 8.43 +/- 5.24 years), admitted to the paediatric gastroenterology unit because of UGIB and who underwent endoscopic examination, were studied from their medical records, retrospectively. RESULTS: Upper gastrointestinal bleeding was observed in 188 (8.29%) of 2266 patients. The mucosal causes related to the oesophagus, stomach and duodenum were found at the rate of 37%, 58% and 24.5%, respectively with endoscopic examination. The location of bleeding could not be determined in 14.4% of the patients. History of drug intake before admitting to hospital was present in 40 patients (21.3%). When we examined these forty patients, 35% were on acetylsalicylic acid, 47.5% were on ibuprofen and 17.5% were on NSAIDs. Ibuprofen versus acetylsalicylic acid usage was found to be highly significant (p < 0.05) for UGIB. Helicobacter pylori was found in 20.7% of the patients. The relationship between H pylori and UGIB was not found statistically significant (p > 0.05). The relationship between drug intake and presence of H pylori infection was not found significant in our patients (p > 0.05). CONCLUSION: Ibuprofen and acetylsalicylic acid intake were found significant in the aetiology of UGIB in children. There was no significant connection with Helicobacter pylori infection in children with UGIB. We did not find a significant relationship with drug intake and H pylori infection. PMID- 26360684 TI - Effect of Submaximal Warm-up Exercise on Exercise-induced Asthma in African School Children. AB - BACKGROUND: Regular physical activity has long been regarded as an important component of a healthy lifestyle. Exercise-induced asthma (EIA) is one of the major problems interfering with the performance of exercise. A warm-up exercise programme has been cited as a non-pharmacologic means of reducing EIA, but its effect has not been fully elucidated. OBJECTIVE: The aims of this study were to determine the prevalence of unrecognized EIA in Pretoria primary school children, determine the effect of a warm-up exercise programme on EIA and to establish the relationship between history of allergy, family history of asthma and EIA. METHODS: A random sample of 640 school children was selected. The study was divided into three phases. In phase one, a descriptive cross-sectional study was done using the standardized European Community Respiratory Health Survey (ECRHS) questionnaire. In phase two, non-asthmatic participants that returned a completed questionnaire were included in the field study. Pre-test and post-test experimental designs were used, where peak expiratory flow rate (PEFR) was measured at baseline and within ten minutes after exercise. A total of 340 subjects completed the Free Running Asthma Screening Test (FRAST); EIA was defined as a decrease in baseline PEFR >= 10% after exercise and 75 children (22%) had EIA. In phase three, 29 of the 75 subjects participated in the warm-up programme which was performed in the laboratory and subjects acted as their own controls. Predefined protocols for the study were followed. RESULTS: Seventy-five (22%) of the 340 participants had EIA. The mean age, height and weight were 10.51 years, 139.26 cm and 33.45 kg, respectively. Exercise-induced asthma symptoms were cough (25%), chest pain (16%), wheeze (12%) and chest tightness (12%). The history of allergy was 75%, family history of allergy 40% and positive history of allergy when near animals, feathers or in dusty areas 38%. Wheezing during or after exercise, wheezing when near animals, feathers or in dusty areas and chest pain was significant (p < 0.05). The mean PEFR after exercise without warm-up was 4.43 L/min. The mean PEFR after exercise (warm-up) was 4.98. The mean percentage change in PEFR between exercise without warm-up and exercise with warm-up was 14.83%. The paired t-test showed a significant difference between PEFR with warm up and PEFR without warm-up (p < 0.05). CONCLUSION: There was a high prevalence of EIA among study participants. Exercise-induced asthma symptoms were significant for wheezing and chest pain. Exercise after warm-up was significant in reducing EIA. This study reports the effect of warm-up exercise on EIA and highlights the need to screen school children for EIA. PMID- 26360685 TI - Blunt Trauma in Paediatric Patients - Experience from a Small Centre. AB - OBJECTIVE: Despite great prevention efforts, blunt abdominal trauma still remains a leading cause of injury, especially in the paediatric population. Abdominal trauma is the main culprit of serious children's injury and the most common area of initially missed diagnosis with a fatal outcome. AIM: The purpose of this study was to determine the incidence, aetiology, grades of abdominal organ injuries, diagnosis, management and outcome of blunt abdominal trauma in a paediatric population. METHOD: This is a retrospective study of 31 patients with isolated parenchymatous abdominal organs, treated in a single centre. Stable patients with no signs of peritonitis and insignificant changes in laboratory findings were managed conservatively. Unstable patients received surgery. RESULTS: The leading cause of injuries were traffic accidents (64.5%), followed by fall from a height (22.5%), bicycle handlebar injuries (6.45%), contact sport and child abuse (3.22% each). The majority of injured children (90.32%) were managed conservatively. Only three patients (9.68%) were operated on due to complete avulsion and organ smash, or devascularization of the injured organs. Diagnostic computed tomography (CT) scan examination was performed on 93.5% of patients. Few patients had grade I and grade V injuries, while the largest proportion of patients had grade III and IV injuries. The most frequently injured organs were the spleen and kidney. There was no mortality. CONCLUSION: The results emphasize that conservative treatment was appropriate for all stable patients with blunt abdominal trauma regardless of organ injury grade. The success of non-operative management depends upon proper patient selection. The choice of non-operative treatment should be based predominantly on physiological response, rather than grade injury on CT scan. PMID- 26360686 TI - Emergency Department Deaths in a Nigerian University Hospital: Deaths Too Many. AB - OBJECTIVES: We reviewed the demographic pattern and distribution of deaths in the emergency department (ED) of the University College Hospital (UCH) in order to identify gaps in the standard of care, thereby providing evidence for intervention and enhanced research in acute care. METHODS: After obtaining institutional ethics approval, we retrospectively studied all deaths in the ED of UCH from January 1 to December 31, 2011. Data were retrieved from the ED's electronic register. RESULTS: During the 12-month period, a total of 10 728 patients attended the emergency centre and 647 deaths occurred, giving a mortality rate of 6.0%. Male deaths constituted 62% of all deaths. The mean age at death was 44.5 +/- 19.1 (range 5 months-92) years. The age group with the highest proportional mortality was 60-69 years (11.4%). Out of all deaths, 295 (45.6%) had alterations of consciousness. Medicine was the specialty with the most deaths (56%), followed by surgery (40%) and lastly, obstetrics and gynaecology (4%). Of the 190 patients that died from trauma, 153 (80.5%) had injury severity score >= 15. Most deaths (75.4%) occurred within 24 hours of arrival and the 12-hour night shift had 322 (50%) of the mortalities. Autopsies were carried out in 36 (5.6%) of the 647 deaths. Of the 36 autopsies, 24 (66.7%) were deaths due to medical causes. CONCLUSION: Mortalities within 24 hours of presentation at the ED of UCH remain high. This calls for an efficient pre hospital care, well-organized emergency transport system, new guidelines, establishment of protocols and regular audit. PMID- 26360687 TI - Previously Activated Psoralen: A Possible Novel Format of Psoralen Used in the Treatment of Graft-versus-host Disease. AB - Graft-versus-host disease (GVHD) is a lethal complication of allogeneic haematopoietic stem cell transplantation which limits its application. Psoralen was utilized in the treatment of GVHD as a second-line method, which is also known as extracorporeal photochemotherapy (ECP). In the process of ECP, mononuclear cells must be isolated from the body in advance then a photosensitizer, 8-methoxypsoralen (8-MOP, 200 MUg/L for the final concentration), would be added to the cell suspension before its exposure to ultraviolet A [UVA; 365 nm, 2J/cm2]. The disposed lymphocytes re-infused into the body account for 5% to 15% of the lymphocytes in the body. The process of ECP is complicated, expensive and very labour intensive, which limits its popularity. We hypothesized that psoralen should be activated by ultraviolet A, and should be kept in activation for a relatively long time before it gets in contact with mononuclear cells. This kind of psoralen is called previously activated psoralen (PAP), which may have the same effects on GVHD as ECP, but would be much easier and economical to work with. PMID- 26360688 TI - Knowledge of and Attitudes toward Medical Professionalism among Students and Junior Doctors in Trinidad and Tobago. AB - BACKGROUND: The past decade has seen an increasing focus on professionalism within the medical school curriculum. This reflects the growing demand for doctors who demonstrate empathy and uphold the altruistic values of the Hippocratic Oath. Such is often challenged by the resource-constrained environments of developing nations requiring uniquely tailored interventions within these regions. PURPOSE: As part of a wider effort to develop training of medical professionalism at our institution, an initiative was pursued to assess the current knowledge about and attitudes toward medical professionalism. METHODS: The study was designed as a cross-sectional descriptive study of fourth and fifth year medical students and junior doctors. A questionnaire was adapted and revised from a previously published study. Questions were grouped into categories pertaining to knowledge about professionalism and attitudes toward professionalism. Overall, 191 questionnaires were analysed (168 students and 23 doctors). RESULTS: Junior doctors' scores were higher than medical students for all knowledge subscales but scores on the attitude subscales were significantly lower than medical students. Overall, in both groups, attitude scores were higher than knowledge scores. There was an overall trend of decreasing attitude scores as persons progressed through their training years and into clinical practice. CONCLUSIONS: Results demonstrate limited knowledge about medical professionalism but good attitudes toward this trait. Taken together, this perhaps highlights a receptivity toward more formal training within this area that is also justified by the marked decline in attitude scores over time. PMID- 26360689 TI - Early Risk Stratification with Dipyridamole Stress Echo in a Patient with Intermediate Lesion in the Right Coronary Artery, 24 Hours after Percutaneous Coronary Intervention. PMID- 26360690 TI - External Iliac Arterial Obstruction Caused by Satinsky Atrauma Forceps in Renal Transplantation. AB - External iliac arterial obstruction is relatively rare in renal transplantation, and may cause surgical failure and ipsilateral leg ischaemia. Prompt diagnosis and management of this kind of complication is essential to rescue the patient and allograft. Four patients with external iliac arterial obstruction caused by Satinsky atrauma forceps in renal transplantation were analysed and summarized. In case one, the obstruction of the external iliac artery distal to the renal allograft caused ipsilateral leg ischaemia. After surgical fixation of the endarterium, the patient recovered from the lower limb ischaemia. In case two, the obstruction of the external iliac artery was located proximal to the renal allograft. Since the endarterial rupture was not found and fixed in time, the renal allograft was lost. The third case was similar to the second. Based on the previous experience, we fixed the endarterium promptly and transplanted the kidney back successfully. In case four, there was endarterial rupture with atherosclerosis located around the anastomosis stoma. After taking out the atherosclerotic plaque and fixing the endarterium, the blood supply of kidney and lower limb was good. External iliac arterial rupture and obstruction caused by Satinsky atrauma forceps in renal transplantation is rare, but may cause severe and depressing outcome. The critical step is to find and fix the impaired endarterium as early as possible. PMID- 26360691 TI - The Hidden Dangers of Beaches: Cardiorespiratory Arrest Induced by Thermal Shock. AB - Thermal shock is widely recognized by modern medicine. Its pathophysiological mechanisms are known, as are its possible consequences, but scientific reports in the literature about clinical cases with severe consequences are sparse. The authors present a case of cardiorespiratory arrest after prolonged sun exposure followed by a dive in the ocean. Other aetiological causes were ruled out, by exclusion, leading to the diagnosis of cardiorespiratory arrest caused by thermal shock. It is important to inform the public in general of the risks of negligent behaviour on the beach. PMID- 26360692 TI - Ovarian Dermoid Cyst Causing Distal Ureteral Obstruction. AB - A case of a 45-year old woman with an ovarian dermoid cyst causing ureteric colic secondary to distal ureteral obstruction is reported. The dermoid cyst was observed on computed tomography to be adjacent to and compressing the distal left ureter and this was confirmed at surgical exploration. Following oophorectomy, the patient's symptoms completely resolved and the excised ovarian cyst was confirmed on pathological evaluation to be a dermoid cyst. This appears to be the first reported case of ureteral obstruction caused by an ovarian dermoid cyst in the English medical literature. PMID- 26360693 TI - Administration of Flumazenil in a Patient with Acute Abamectin Intoxication: Case Report and Review of the Literature. AB - Abamectin is used in several countries as a type of macrocyclic lactone insecticide to control nematodes and other pests in livestock and agriculture. This medicine, used for animals and crops, would be highly toxic to human if a person has intentional poisoning. We report a case of a 47-year old man who was admitted to the hospital after ingestion of a large dose of abamectin on purpose, and who rapidly recovered consciousness after administration of flumazenil. Although flumazenil is not the antidote of abamectin, we may hypothesize that it could reduce recovery time and shorten expenditures in hospital. This is the first report that focusses on a specific treatment which could possibly accelerate recovery of consciousness for patients with abamectin intoxication. PMID- 26360694 TI - Lactic Acidosis during Entecavir Antiviral Treatment in a Patient with Hepatitis B Virus-related Decompensated Cirrhosis. PMID- 26360695 TI - A Bullous Pilomatricoma Developed after Hepatitis A Vaccination. PMID- 26360696 TI - Can Isotretinoin Induce Articular Symptoms in SAPHO Syndrome? PMID- 26360697 TI - Toxoplasma Chorioretinitis Subsequent to Anti-tumour Necrosis Factor Alpha Treatment in a Patient with Ankylosing Spondylitis. PMID- 26360698 TI - Intracranial Subdural Haematoma after Thoracic Epidural without Signs of Dural Puncture. PMID- 26360699 TI - Rhabdomyolysis and Dengue Fever: Is This More Common Than We Think? PMID- 26360700 TI - Bone histology in extant and fossil penguins (Aves: Sphenisciformes). AB - Substantial changes in bone histology accompany the secondary adaptation to life in the water. This transition is well documented in several lineages of mammals and non-avian reptiles, but has received relatively little attention in birds. This study presents new observations on the long bone microstructure of penguins, based on histological sections from two extant taxa (Spheniscus and Aptenodytes) and eight fossil specimens belonging to stem lineages (?Palaeospheniscus and several indeterminate Eocene taxa). High bone density in penguins results from compaction of the internal cortical tissues, and thus penguin bones are best considered osteosclerotic rather than pachyostotic. Although the oldest specimens sampled in this study represent stages of penguin evolution that occurred at least 25 million years after the loss of flight, major differences in humeral structure were observed between these Eocene stem taxa and extant taxa. This indicates that the modification of flipper bone microstructure continued long after the initial loss of flight in penguins. It is proposed that two key transitions occurred during the shift from the typical hollow avian humerus to the dense osteosclerotic humerus in penguins. First, a reduction of the medullary cavity occurred due to a decrease in the amount of perimedullary osteoclastic activity. Second, a more solid cortex was achieved by compaction. In extant penguins and ?Palaeospheniscus, most of the inner cortex is formed by rapid osteogenesis, resulting an initial latticework of woven-fibered bone. Subsequently, open spaces are filled by slower, centripetal deposition of parallel-fibered bone. Eocene stem penguins formed the initial latticework, but the subsequent round of compaction was less complete, and thus open spaces remained in the adult bone. In contrast to the humerus, hindlimb bones from Eocene stem penguins had smaller medullary cavities and thus higher compactness values compared with extant taxa. Although cortical lines of arrested growth have been observed in extant penguins, none was observed in any of the current sampled specimens. Therefore, it is likely that even these 'giant' penguin taxa completed their growth cycle without a major pause in bone deposition, implying that they did not undergo a prolonged fasting interval before reaching adult size. PMID- 26360701 TI - A Novel GH7 Endo-beta-1,4-Glucanase from Neosartorya fischeri P1 with Good Thermostability, Broad Substrate Specificity and Potential Application in the Brewing Industry. AB - An endo-beta-1,4-glucanase gene, cel7A, was cloned from the thermophilic cellulase-producing fungus Neosartorya fischeri P1 and expressed in Pichia pastoris. The 1,410-bp full-length gene encodes a polypeptide of 469 amino acids consisting of a putative signal peptide at residues 1-20, a catalytic domain of glycoside hydrolase family 7 (GH7), a short Thr/Ser-rich linker and a family 1 carbohydrate-binding module (CBM 1). The purified recombinant Cel7A had pH and temperature optima of pH 5.0 and 60 degrees C, respectively, and showed broad pH adaptability (pH 3.0-6.0) and excellent stability at pH3.0-8.0 and 60 degrees C. Belonging to the group of nonspecific endoglucanases, Cel7A exhibited the highest activity on barley beta-glucan (2020 +/- 9 U mg-1), moderate on lichenan and CMC Na, and weak on laminarin, locust bean galactomannan, Avicel, and filter paper. Under simulated mashing conditions, addition of Cel7A (99 MUg) reduced the mash viscosity by 9.1% and filtration time by 24.6%. These favorable enzymatic properties make Cel7A as a good candidate for applications in the brewing industry. PMID- 26360702 TI - Uncoupling of Protein Aggregation and Neurodegeneration in a Mouse Amyotrophic Lateral Sclerosis Model. AB - Aberrant accumulation of protein aggregates is a pathological hallmark of many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Although a buildup of protein aggregates frequently leads to cell death, whether it is the key pathogenic factor in driving neurodegenerative disease remains controversial. HDAC6, a cytosolic ubiquitin-binding deacetylase, has emerged as an important regulator of ubiquitin-dependent quality control autophagy, a lysosome-dependent degradative system responsible for the disposal of misfolded protein aggregates and damaged organelles. Here, we show that in cell models HDAC6 plays a protective role against multiple disease-associated and aggregation prone cytosolic proteins by facilitating their degradation. We further show that HDAC6 is required for efficient localization of lysosomes to protein aggregates, indicating that lysosome targeting to autophagic substrates is regulated. Supporting a critical role of HDAC6 in protein aggregate disposal in vivo, genetic ablation of HDAC6 in a transgenic SOD1G93A mouse, a model of ALS, leads to dramatic accumulation of ubiquitinated SOD1G93A protein aggregates. Surprisingly, despite a robust buildup of SOD1G93A aggregates, deletion of HDAC6 only moderately modified the motor phenotypes. These findings indicate that SOD1G93A aggregation is not the only determining factor to drive neurodegeneration in ALS, and that HDAC6 likely modulates neurodegeneration through additional mechanisms beyond protein aggregate clearance. PMID- 26360703 TI - Cholelithiasis and Nephrolithiasis in HIV-Positive Patients in the Era of Combination Antiretroviral Therapy. AB - OBJECTIVES: This study aimed to describe the epidemiology and risk factors of cholelithiasis and nephrolithiasis among HIV-positive patients in the era of combination antiretroviral therapy. METHODS: We retrospectively reviewed the medical records of HIV-positive patients who underwent routine abdominal sonography for chronic viral hepatitis, fatty liver, or elevated aminotransferases between January 2004 and January 2015. Therapeutic drug monitoring of plasma concentrations of atazanavir was performed and genetic polymorphisms, including UDP-glucuronosyltransferase (UGT) 1A1*28 and multidrug resistance gene 1 (MDR1) G2677T/A, were determined in a subgroup of patients who received ritonavir-boosted or unboosted atazanavir-containing combination antiretroviral therapy. Information on demographics, clinical characteristics, and laboratory testing were collected and analyzed. RESULTS: During the 11-year study period, 910 patients who underwent routine abdominal sonography were included for analysis. The patients were mostly male (96.9%) with a mean age of 42.2 years and mean body-mass index of 22.9 kg/m2 and 85.8% being on antiretroviral therapy. The anchor antiretroviral agents included non-nucleoside reverse-transcriptase inhibitors (49.3%), unboosted atazanavir (34.4%), ritonavir boosted lopinavir (20.4%), and ritonavir-boosted atazanavir (5.5%). The overall prevalence of cholelithiasis and nephrolithiasis was 12.5% and 8.2%, respectively. Among 680 antiretroviral-experienced patients with both baseline and follow-up sonography, the crude incidence of cholelithiasis and nephrolithiasis was 4.3% and 3.7%, respectively. In multivariate analysis, the independent factors associated with incident cholelithiasis were exposure to ritonavir-boosted atazanavir for >2 years (adjusted odds ratio [AOR], 6.29; 95% confidence interval [CI], 1.12-35.16) and older age (AOR, 1.04; 95% CI, 1.00 1.09). The positive association between duration of exposure to ritonavir-boosted atazanavir and incident cholelithiasis was also found (AOR, per 1-year exposure, 1.49; 95% CI, 1.05-2.10). The associated factors with incident nephrolithiasis were hyperlipidemia (AOR, 3.97; 95% CI, 1.32-11.93), hepatitis B or C coinfection (AOR, 3.41; 95% CI, 1.09-10.62), and exposure to abacavir (AOR, 12.01; 95% CI, 1.54-93.54). Of 180 patients who underwent therapeutic drug monitoring of plasma atazanavir concentrations and pharmacogenetic investigations, we found that the atazanavir concentrations and UGT 1A1*28 and MDR1 G2677T/A polymorphisms were not statistically significantly associated with incident cholelithiasis and nephrolithiasis. CONCLUSIONS: In HIV-positive patients in the era of combination antiretroviral therapy, a high prevalence of cholelithiasis and nephrolithiasis was observed, and exposure to ritonavir-boosted atazanavir for >2 years was associated with incident cholelithiasis. PMID- 26360704 TI - Potential Therapeutic Value of a Novel FAAH Inhibitor for the Treatment of Anxiety. AB - Anxiety disorders are among the most prevalent psychiatric diseases with high personal costs and a remarkable socio-economic burden. However, current treatment of anxiety is far from satisfactory. Novel pharmacological targets have emerged in the recent years, and attention has focused on the endocannabinoid (eCB) system, given the increasing evidence that supports its central role in emotion, coping with stress and anxiety. In the management of anxiety disorders, drug development strategies have left apart the direct activation of type-1 cannabinoid receptors to indirectly enhance eCB signalling through the inhibition of eCB deactivation, that is, the inhibition of the fatty acid amide hydrolase (FAAH) enzyme. In the present study, we provide evidence for the anxiolytic-like properties of a novel, potent and selective reversible inhibitor of FAAH, ST4070, orally administered to rodents. ST4070 (3 to 30 mg/kg per os) administered to CD1 male mice induced an increase of time spent in the exploration of the open arms of the elevated-plus maze. A partial reduction of anxiety-related behaviour by ST4070 was also obtained in Wistar male rats, which moderately intensified the time spent in the illuminated compartment of the light-dark box. ST4070 clearly inhibited FAAH activity and augmented the levels of two of its substrates, N arachidonoylethanolamine (anandamide) and N-palmitoylethanolamine, in anxiety relevant brain regions. Altogether, ST4070 offers a promising anxiolytic-like profile in preclinical studies, although further studies are warranted to clearly demonstrate its efficacy in the clinic management of anxiety disorders. PMID- 26360705 TI - Inhibition of JAK2 Reverses Paclitaxel Resistance in Human Ovarian Cancer Cells. AB - OBJECTIVE: Resistance to chemotherapy is a major factor that limits the postsurgical survival of ovarian cancer patients. Janus-activated kinase 2 (JAK2) has been implicated in cancer cell survival and the development of drug resistance in ovarian cancers. In the present study, we sought to determine whether inhibition of JAK2 reverses drug resistance in OC3/TAX300 cells, a paclitaxel-resistant human ovarian cancer cell line previously established in our laboratory. METHODS: OC3/TAX300 cells were transduced with lentivirus expressing small interference RNA (siRNA) against JAK2 and treated with JAK2 kinase inhibitor AG490. RESULTS: Treatment with JAK2-siRNA markedly decreased the messenger RNA and protein of JAK2 as determined by real-time polymerase chain reaction and Western blot analysis. OC3/TAX300 cells treated with JAK2-siRNA exhibited stalled growth, increased cell cycle arrest in G2/M phase, and enhanced apoptosis in response to paclitaxel. In keeping with this, JAK2-siRNA also inhibited the expression of multidrug resistance protein 1. To determine whether JAK2 promotes paclitaxel resistance via phosphorylation of signal transducer and activator of transcription 3 (STAT3), a transcription factor known to be involved in resistance to chemotherapy, we treated OC3/TAX300 cells with JAK2 kinase inhibitor AG490. Of note, AG490 reduced the level of p-STAT3 and inhibited the expression of multidrug resistance protein 1 in a dose-dependent manner. CONCLUSIONS: Collectively, we conclude that the JAK2-STAT3 pathway promotes the development of paclitaxel resistance via upregulating the expression of prosurvival and antiapoptotic genes. Targeting this pathway may be effective in reversing resistance to chemotherapy in ovarian cancers. PMID- 26360706 TI - One-sided and mutually aggressive couples: Differences in attachment, conflict prevalence, and coping. AB - This study investigated concurrent links between adolescent romantic couples' reports of aggression (relational and physical) and relationship functioning (e.g., attachment security, conflict prevalence, coping strategies, jealousy, and affiliative and romantic relationship quality) using a pattern-oriented approach. The sample included 194 romantic partner dyads (Mage=16.99 years for females and Mage=18.41 years for males). A hierarchical cluster analysis identified five distinct subgroups of dyads based on male and female reports of relational and physical aggression, ranging from nonaggressive couples (42%), to those characterized by aggressive females (18%), aggressive males (14%), physically aggressive females (20%), and mutually aggressive females and males (6%). Clusters in which one partner was perceived as either relationally or physically aggressive were characterized by higher rates of conflict, less adaptive coping, and more jealousy (particularly in males). The mutually aggressive couples showed the least adaptive relationship functioning, with high rates of conflict, a deficit in reflection and emotion regulation in conflict situations, and a lack of affiliative relationship qualities. The discussion focuses on the formative character of aggression in these early romantic relations, the aggravating impact of mutual aggression on relationship functioning, and the gender-specific functions of aggression in relationships characterized by unilateral aggression. PMID- 26360707 TI - Protecting children from all forms of violence. PMID- 26360708 TI - Empowering and protecting children by enhancing knowledge, skills and well-being: A randomized trial of Learn to BE SAFE with Emmy. AB - Australia needs effective programs to protect children and prevent abuse, but there is little information available for policymakers or families. Using a randomized controlled trial, Learn to BE SAFE with Emmy, a school-based protection program for young children designed by Act for Kids, was evaluated to determine its effectiveness for promoting young children's knowledge and skills. Grade one children (n=245) from 15 classrooms across 5 primary schools completed assessment measures. A subset of these children received the program (n=131) or acted as a comparison group (n=114). Parents (n=72) completed questionnaires about their child's participation in the program. When compared with children who had not received the program, children who completed Learn to BE SAFE with Emmy demonstrated increased knowledge of interpersonal safety and were more likely to choose a safe response option to hypothetical unsafe scenarios 6 months after participation than at both pre- and post-intervention. Parents reported their children who participated used more safety strategies immediately and 6 months after participation compared to pre-intervention. Outcomes can assist in guiding future policies around the prevention of child abuse and protect the well-being of Australian children. PMID- 26360710 TI - Effects of a contact lens subscriber replacement program on patient lens care behavior in Japan. AB - PURPOSE: Compliance with practitioner recommended lens care guidelines was assessed and compared in two test groups: patients belonging to a subscription membership group and a nonaffiliated group of 2-week frequent replacement (2WFR) soft contact lens wearers. METHODS: Wearers (143 members and 149 nonmembers), whose clinical records were available for 18-24 months from September 2010 to August 2012, were queried by a written questionnaire: (1) source of lens purchase; (2) "rub" or "no-rub" care solution; (3) replacement interval of lens care products; (4) lens cleaning method; (5) noncompliant behaviors; and (6) replacement frequency of lens storage cases. RESULTS: The questionnaires were completed by 104 members and 100 nonmembers. Of member group wearers, 63.0% correctly recognized the types of lens care products used ("rub', "no-rub") vs. 77.4% of nonmembers. Of member wearers, 82.2% used "rub" and rubbed each time vs. 76.3% of nonmembers. The replacement interval for care products was 26.2% (members) and 27.6% (nonmembers) for 1 month or less, while replacement frequency of storage cases was 22.3% and 19.2% for 1 month or less in each group respectively. There were no significant differences observed between each of these group comparisons (p>0.05, Fisher exact test). CONCLUSIONS: Compliance with practitioner recommended lens care regimens was equally poor in both test groups. Subscription membership of CLs which does not provide lens care products is not accompanied by an increase in compliance with lens care practices. PMID- 26360711 TI - Physical and mental health: activate and integrate. PMID- 26360712 TI - Anxiety prevention in schools. PMID- 26360709 TI - Simian Immunodeficiency Virus Infection of Chimpanzees (Pan troglodytes) Shares Features of Both Pathogenic and Non-pathogenic Lentiviral Infections. AB - The virus-host relationship in simian immunodeficiency virus (SIV) infected chimpanzees is thought to be different from that found in other SIV infected African primates. However, studies of captive SIVcpz infected chimpanzees are limited. Previously, the natural SIVcpz infection of one chimpanzee, and the experimental infection of six chimpanzees was reported, with limited follow-up. Here, we present a long-term study of these seven animals, with a retrospective re-examination of the early stages of infection. The only clinical signs consistent with AIDS or AIDS associated disease was thrombocytopenia in two cases, associated with the development of anti-platelet antibodies. However, compared to uninfected and HIV-1 infected animals, SIVcpz infected animals had significantly lower levels of peripheral blood CD4+ T-cells. Despite this, levels of T-cell activation in chronic infection were not significantly elevated. In addition, while plasma levels of beta2 microglobulin, neopterin and soluble TNF related apoptosis inducing ligand (sTRAIL) were elevated in acute infection, these markers returned to near-normal levels in chronic infection, reminiscent of immune activation patterns in 'natural host' species. Furthermore, plasma soluble CD14 was not elevated in chronic infection. However, examination of the secondary lymphoid environment revealed persistent changes to the lymphoid structure, including follicular hyperplasia in SIVcpz infected animals. In addition, both SIV and HIV-1 infected chimpanzees showed increased levels of deposition of collagen and increased levels of Mx1 expression in the T-cell zones of the lymph node. The outcome of SIVcpz infection of captive chimpanzees therefore shares features of both non-pathogenic and pathogenic lentivirus infections. PMID- 26360713 TI - Intervening to prevent suicide. PMID- 26360714 TI - Recovering from alcohol dependence. PMID- 26360715 TI - Pregnancy and suicide: towards a coherent narrative. PMID- 26360716 TI - A new model of community care. PMID- 26360717 TI - The Wakley Essay Prize 2014: the best of both worlds. PMID- 26360718 TI - Corrections. PMID- 26360719 TI - Antipsychiatry and the antidepressants debate. PMID- 26360720 TI - Strengthening civil and political rights of people with mental illness. PMID- 26360721 TI - Antipsychiatry and the antidepressants debate. PMID- 26360722 TI - Effects of patient suicide on the multidisciplinary care team. PMID- 26360724 TI - Coercion and human rights in Czech psychiatry: a human rights perspective from MDAC. PMID- 26360725 TI - Wanting to be normal. PMID- 26360726 TI - Drawn from memory. PMID- 26360727 TI - Sad stories of the death of Kings. PMID- 26360728 TI - Freedom of expression. PMID- 26360729 TI - The age of anxiety. PMID- 26360730 TI - Classroom-based cognitive behaviour therapy (FRIENDS): a cluster randomised controlled trial to Prevent Anxiety in Children through Education in Schools (PACES). AB - BACKGROUND: Anxiety in children is common, impairs everyday functioning, and increases the risk of severe mental health disorders in adulthood. We investigated the effect of a classroom-based cognitive behaviour therapy prevention programme (FRIENDS) on anxiety symptoms in children. METHODS: Preventing Anxiety in Children though Education in Schools (PACES) is a three group parallel cluster randomised controlled trial. Interventions were given between September, 2011, and July, 2012, with schools as the unit of allocation and individual participants as the unit of analysis. We enrolled state-funded junior schools in southwest England. We sent information to all eligible schools (state-funded junior schools in southwest England) inviting them to enrol in the study. School year groups were assigned by computer-generated randomisation (1:1:1) to receive either school-led FRIENDS (led by teacher or school staff member), health-led FRIENDS (led by two trained health facilitators), or usual school provision. Children were not masked to treatment allocation. The allocated programme was given to all students (aged 9-10 years) in the school year (ie, universal delivery) as part of the school curriculum as nine, 60 min weekly sessions. Outcomes were collected by self-completed questionnaire administered by researchers masked to allocation. Primary outcome was symptoms of anxiety and low mood at 12 months assessed by the Revised Child Anxiety and Depression Scale (RCADS 30). Analyses were intention to treat and accounted for the clustered nature of the design. The study is registered, number ISRCTN23563048. FINDINGS: 45 schools were enrolled: 14 (n=497 children) were randomly assigned to school led FRIENDS, 14 (n=509) to health-led FRIENDS, and 12 (n=442) to usual school provision. 1257 (92%) children completed 12 month assessments (449 in health-led FRIENDS, 436 in school-led FRIENDS, and 372 in usual school provision). We recorded a difference at 12 months in adjusted mean child-reported RCADS scores for health-led versus school-led FRIENDS (19.49 [SD 14.81] vs 22.86 [15.24]; adjusted difference -3.91, 95% CI -6.48 to -1.35; p=0.0004) and health-led FRIENDS versus usual school provision (19.49 [14.81] vs 22.48 [15.74]; -2.66, 5.22 to -0.09; p=0.043). We noted no differences in parent or teacher ratings. Training teachers to deliver mental health programmes was not as effective as delivery by health professionals. INTERPRETATION: Universally delivered anxiety prevention programmes can be effective when used in schools. However, programme effectiveness varies depending on who delivers them. FUNDING: National Institute for Health Research Public Health Research Programme. PMID- 26360731 TI - Assertive case management versus enhanced usual care for people with mental health problems who had attempted suicide and were admitted to hospital emergency departments in Japan (ACTION-J): a multicentre, randomised controlled trial. AB - BACKGROUND: Non-fatal suicide attempt is the most important risk factor for later suicide. Emergency department visits for attempted suicide are increasingly recognised as opportunities for intervention. However, no strong evidence exists that any intervention is effective at preventing repeated suicide attempts. We aimed to investigate whether assertive case management can reduce repetition of suicide attempts in people with mental health problems who had attempted suicide and were admitted to emergency departments. METHODS: In this multicentre, randomised controlled trial in 17 hospital emergency departments in Japan, we randomly assigned people aged 20 years and older with mental health problems who had attempted suicide to receive either assertive case management (based on psychiatric diagnoses, social risks, and needs of the patients) or enhanced usual care (control), using an internet-based randomisation system. Interventions were provided until the end of the follow-up period (ie, at least 18 months and up to 5 years). Outcome assessors were masked to group allocation, but patients and case managers who provided the interventions were not. The primary outcome was the incidence of first recurrent suicidal behaviour (attempted suicide or completed suicide); secondary outcomes included completed suicide and all-cause mortality. This study is registered at ClinicalTrials.gov (NCT00736918) and UMIN CTR (C000000444). FINDINGS: Between July 1, 2006, and Dec 31, 2009, 914 eligible participants were randomly assigned, 460 to the assertive case management group and 456 to the enhanced usual care group. We noted no significant difference in incidence of first recurrent suicidal behaviour between the assertive case management group and the enhanced usual care group over the full study period (log-rank p=0.258). Because the proportional hazards assumption did not hold, we did ad-hoc analyses for cumulative incidence of the primary outcome at months 1, 3, 6, 12, and 18 after randomisation, adjusting for multiplicity with the Bonferroni method. Assertive case management significantly reduced the incidence of first recurrent suicidal behaviour up to the 6-month timepoint (6-month risk ratio 0.50, 95% CI 0.32-0.80; p=0.003), but not at the later timepoints. Prespecified subgroup analyses showed that the intervention had a greater effect in women (up to 18 months), and in participants younger than 40 years and those with a history of previous suicide attempts (up to 6 months). We did not identify any differences between the intervention and control groups for completed suicide (27 [6%] of 460 vs 30 [7%] of 454, log-rank p=0.660) or all-cause mortality (46 [10%] of 460 vs 42 [9%] of 454, log-rank p=0.698). INTERPRETATION: Our results suggest that assertive case management is feasible in real-world clinical settings. Although it was not effective at reducing the incidence of repetition of suicide attempts in the long term, the results of our ad-hoc analyses suggested that it was effective for up to 6 months. This finding should be investigated in future research. FUNDING: The Ministry of Health, Labour, and Welfare of Japan. PMID- 26360732 TI - White matter microstructural recovery with abstinence and decline with relapse in alcohol dependence interacts with normal ageing: a controlled longitudinal DTI study. AB - BACKGROUND: Alcohol dependence exacts a toll on brain white matter microstructure, which has the potential of repair with prolonged sobriety. Diffusion tensor imaging (DTI) enables in-vivo quantification of tissue constituents and localisation of tracts potentially affected in alcohol dependence and its recovery. We did an extended longitudinal study of alcoholism's trajectory of effect on selective fibre bundles with sustained sobriety or decline with relapse. METHODS: Participants were drawn from a longitudinal, 1.5T DTI database of 841 scans of individuals with various medical or neuropsychiatric conditions and normal ageing. Participants diagnosed with alcohol dependence had to meet the criteria from DSM-IV for alcohol dependence. Controls were screened and free of any DSM-IV axis I diagnosis, including being without history of alcohol or drug abuse or dependence. Tract-based spatial statistics (TBSS) quantified white matter integrity throughout the brain in 47 alcohol-dependent individuals and 56 controls examined 2-5 times over 1-8 year intervals. We identified regions showing group differences with a white matter atlas. For macrostructural comparison, we measured corpus callosum and centrum semiovale volumes on MRI. FINDINGS: This study took place in the USA, between June 23, 2000, and Sept 6, 2011. TBSS identified a large cluster (threshold p<0.001), where controls showed significant fractional anisotropy (FA) decrease with ageing and alcohol-dependent individuals had significantly lower FA than controls regardless of age. Over the examination interval, 27 (57%) alcohol dependent individuals abstained, ten (21%) relapsed into light drinking, and ten (21%) relapsed into heavy drinking (>5 kg of alcohol/year). Despite abnormally low FA, age trajectories of the abstainers were positive and progressing toward normality, whereas those of the relapsers and controls were negative. Axial diffusivity (lower values indexing myelin integrity) was abnormally high in the total alcohol-dependent group; however, the abstainers' slopes paralleled those of controls, whereas the heavy-drinking relapsers' slopes showed accelerated ageing. Callosal genu and body microstructure but not macrostructure showed untoward alcohol-related effects. Affected projection and association tracts had an anterior and superior neuroanatomical distribution. INTERPRETATION: Return to heavy drinking resulted in accelerating microstructural white matter damage. Despite evidence for damage, alcohol-dependent individuals maintaining sobriety over extended periods showed improvement in brain fibre tract integrity reflective of fibre reorganisation and myelin restoration, indicative of a neural mechanism explaining recovery. FUNDING: US National Institute on Alcohol Abuse and Alcoholism (AA012388, AA017168, AA005965, AA013521-INIA). PMID- 26360734 TI - Dissociative amnesia. AB - Dissociative amnesia is one of the most enigmatic and controversial psychiatric disorders. In the past two decades, interest in the understanding of its pathophysiology has surged. In this report, we review new data about the epidemiology, neurobiology, and neuroimaging of dissociative amnesia and show how advances in memory research and neurobiology of dissociation inform proposed pathogenetic models of the disorder. Dissociative amnesia is characterised by functional impairment. Additionally, preliminary data suggest that affected people have an increased and possibly underestimated suicide risk. The prevalence of dissociative amnesia differs substantially across countries and populations. Symptoms and disease course also vary, indicating a possibly heterogeneous disorder. The accompanying clinical features differ across cultural groups. Most dissociative amnesias are retrograde, with memory impairments mainly involving the episodic-autobiographical memory domain. Anterograde dissociative amnesia occurring without significant retrograde memory impairments is rare. Functional neuroimaging studies of dissociative amnesia with prevailing retrograde memory impairments show changes in the network that subserves autobiographical memory. At present, no evidence-based treatments are available for dissociative amnesia and no broad framework exists for its rehabilitation. Further research is needed into its neurobiology, course, treatment options, and strategies to improve differential diagnoses. PMID- 26360733 TI - Contribution of suicide and injuries to pregnancy-related mortality in low-income and middle-income countries: a systematic review and meta-analysis. AB - BACKGROUND: Although suicide is one of the leading causes of deaths in young women in low-income and middle-income countries, the contribution of suicide and injuries to pregnancy-related mortality remains unknown. METHODS: We did a systematic review to identify studies reporting the proportion of pregnancy related deaths attributable to suicide or injuries, or both, in low-income and middle-income countries. We used a random-effects meta-analysis to calculate the pooled prevalence of pregnancy-related deaths attributable to suicide, stratified by WHO region. To account for the possible misclassification of suicide deaths as injuries, we calculated the pooled prevalence of deaths attributable to injuries, and undertook a sensitivity analysis reclassifying the leading methods of suicides among women in low-income and middle-income countries (burns, poisoning, falling, or drowning) as suicide. FINDINGS: We identified 36 studies from 21 countries. The pooled total prevalence across the regions was 1.00% for suicide (95% CI 0.54-1.57) and 5.06% for injuries (3.72-6.58). Reclassifying the leading suicide methods from injuries to suicide increased the pooled prevalence of pregnancy-related deaths attributed to suicide to 1.68% (1.09-2.37). Americas (3.03%, 1.20-5.49), the eastern Mediterranean region (3.55%, 0.37-9.37), and the southeast Asia region (2.19%, 1.04-3.68) had the highest prevalence for suicide, with the western Pacific (1.16%, 0.00-4.67) and Africa (0.65%, 0.45-0.88) regions having the lowest. INTERPRETATION: The available data suggest a modest contribution of injuries and suicide to pregnancy-related mortality in low-income and middle-income countries with wide regional variations. However, this study might have underestimated suicide deaths because of the absence of recognition and inclusion of these causes in eligible studies. We recommend that injury related and other co-incidental causes of death are included in the WHO definition of maternal mortality to promote measurement and effective intervention for reduction of maternal mortality in low-income and middle-income countries. FUNDING: National Institute of Mental Health. PMID- 26360735 TI - Psychoanalytic ideas and their place in psychiatry training in the UK. PMID- 26360737 TI - Complex regional pain syndrome type I in children. Clinical description and quality of life. AB - INTRODUCTION: Complex regional pain syndrome type 1 (CRPS I) in children differs from its adult counterpart and relevant literature is scarce. Our aim was to investigate potential risk factors and to assess midterm outcome and quality of life. MATERIAL AND METHODS: Medical records of patients diagnosed with CRPS I between 2004 and 2012 were analyzed. Patients and parents were called for a phone interview including the PEDS Quality of Life 4-0 questionnaire. Results were compared to a control group matched for age, gender and socio-economic status. RESULTS: Seventy-three patients were included (64 girls, 9 boys). Mean age at diagnosis was 11.5 years and mean time to diagnosis was 14.2 months. The lower limb was affected in 89% of cases. Allodynia, coldness and cyanosis were noted in 95%, 81% and of 74% of cases, respectively. Forty-nine percent of patients reported a physical injury. Multivariate analysis showed a strong association with being anxious (OR = 44.9, 95% CI [7.4-273]), presence of an atopic background (OR = 25.0, 95% CI: [4.6-135]), being good to excellent school performers (OR = 8.4 95% CI [1.3-52.1]), and having trouble falling asleep (OR = 5.3, 95% CI [1.6-17.0]). At a mean 37 months' follow-up (12-102), PEDS QL 4-0 score was significantly lower in CRPS patients compared to controls. Fifty-seven percent of patients acknowledged healing and 55% had presented a relapse. CONCLUSION: Childhood onset CRPS I affects predominantly preadolescent girls at the ankle. The present study highlights the relatively poor outcome, especially its physical and emotional aspects and the large role of psychology. LEVEL OF EVIDENCE: IV. PMID- 26360736 TI - Passive Leg Raising Correlates with Future Exercise Capacity after Coronary Revascularization. AB - Hemodynamic properties affected by the passive leg raise test (PLRT) reflect cardiac pumping efficiency. In the present study, we aimed to further explore whether PLRT predicts exercise intolerance/capacity following coronary revascularization. Following coronary bypass/percutaneous coronary intervention, 120 inpatients underwent a PLRT and a cardiopulmonary exercise test (CPET) 2-12 days during post-surgery hospitalization and 3-5 weeks after hospital discharge. The PLRT included head-up, leg raise, and supine rest postures. The end point of the first CPET during admission was the supra-ventilatory anaerobic threshold, whereas that during the second CPET in the outpatient stage was maximal performance. Bio-reactance-based non-invasive cardiac output monitoring was employed during PLRT to measure real-time stroke volume and cardiac output. A correlation matrix showed that stroke volume during leg raise (SVLR) during the first PLRT was positively correlated (R = 0.653) with the anaerobic threshold during the first CPET. When exercise intolerance was defined as an anaerobic threshold < 3 metabolic equivalents, SVLR / body weight had an area under curve value of 0.822, with sensitivity of 0.954, specificity of 0.593, and cut-off value of 1504.10-3mL/kg (positive predictive value 0.72; negative predictive value 0.92). Additionally, cardiac output during leg raise (COLR) during the first PLRT was related to peak oxygen consumption during the second CPET (R = 0.678). When poor aerobic fitness was defined as peak oxygen consumption < 5 metabolic equivalents, COLR / body weight had an area under curve value of 0.814, with sensitivity of 0.781, specificity of 0.773, and a cut-off value of 68.3 mL/min/kg (positive predictive value 0.83; negative predictive value 0.71). Therefore, we conclude that PLRT during hospitalization has a good screening and predictive power for exercise intolerance/capacity in inpatients and early outpatients following coronary revascularization, which has clinical significance. PMID- 26360738 TI - Construction and evaluation of PAMAM-DOX conjugates with superior tumor recognition and intracellular acid-triggered drug release properties. AB - An ideal drug delivery system for cancer therapy should be equipped with extended circulation, improved tumor targeting and controlled drug release, as well as low toxicity from the carrier. In this study, a multifunctional drug delivery system based on the PEGylated poly(amidoamine) (PAMAM) dendrimer was designed, and folate-PEGylation was applied to modify the dendrimer in order to enhance tumor selectivity. A series of acid-labile PAMAM-DOX conjugates (FPP-hyd-DOX) with different FA ligand ratios were successfully constructed. (1)H NMR, FTIR, DLS and TEM were used to describe the physicochemical characterization of PAMAM-DOX conjugates. Both in vitro drug release assay and subcellular localization, the conjugates exhibited an obvious pH-triggered drug release. The FPP-hyd-DOX 16/1 displayed much lower IC50 value than that of non-targeted PP-hyd-DOX. Through fluorescence microscopy and flow cytometry investigations, the cellular uptake of FPP-hyd-DOX 16/1 was obviously enhanced, compared with that of PP-hyd-DOX. The cellular uptake mechanism and subcellular localization study revealed that the conjugates were internalized by KB cells via FA receptor and clathrin co-mediated endocytosis, delivered to acidic lysosomes and triggered the release of DOX into nuclei to exert its cytotoxicity. These obtained results showed that FPP-hyd-DOX conjugations would be a promising drug delivery carrier for targeted cancer therapy. PMID- 26360739 TI - Redefining major hepatic resection for colorectal liver metastases: Analysis of 1111 liver resections. AB - INTRODUCTION: A major hepatic resection is currently defined as resection of 3 or more segments. The aim of this study was to analyse the post-operative morbidity and mortality of hepatic resections in relation to the number of segments excised. PATIENTS AND METHODS: From January 2000 to December 2010, 1111 liver resections were performed for colorectal liver metastases (CRLM). Data were collected from a prospectively maintained database and analysed according to the extent of resection performed. RESULTS: 457 patients had 1-2, 362 had 3-4 and 292 had 5-6 segments resected respectively. In comparing 1-4 vs. 5-6 segments, overall morbidity (16.7% vs 40.7%; p < 0.001), hepatic failure (0.6% vs 10.6%; p < 0.001); mean hospital stay (8 vs 13.5 days; p = 0.000), mean ICU stay (4.4 vs 6.5 days; p = 0.01), 60-day mortality (0.7% vs 3.4%; p = 0.002), and 90-day mortality (0.7% vs 3.4%; p = 0.002) were significantly different. When analysing the 3-4 vs 5-6 segment resections, morbidity (21.8% vs 40.7%; p < 0.001), hepatic failure (1.4% vs 10.6%; p = 0.000), 60-day mortality (0.7% vs 3.4%; p = 0.002), and 90-days mortality (0.8% vs 3.4%; p = 0.023) remained statistically significant. CONCLUSIONS: Differences in outcome would suggest a revision of the current classification. Only when 5 or more segments are excised for CRLM should a liver resection be considered "major". PMID- 26360740 TI - A Chinese randomized prospective trial of floppy Nissen and Toupet fundoplication for gastroesophageal disease. AB - INTRODUCTION: To evaluate the clinical outcomes of laparoscopic floppy Nissen fundoplication (LNF) and laparoscopic Toupet fundoplication (LTF) for the treatment of gastroesophageal disease (GERD). METHODS: A total of 84 patients with GERD were randomized to either LNF (n = 43) or LTF (n = 41) between January 2010 and January 2013. The primary endpoint measures were the DeMeester score, distal esophageal amplitude (DEA), peristaltic frequency, lower esophageal sphincter pressure (LESP), short-term and long-term postoperative dysphagia and recurrence rate. The secondary endpoints were improvements in symptom scores and quality of life (QoL), and perioperative complications. RESULTS: LNF group had a lower DeMeester score and a higher LESP compared to LTF group after surgery (DeMeester score: P = 0.007; LESP: P = 0.027). The mean DEA and peristaltic frequency both improved significantly after surgery in 2 groups. There was no difference in the incidence of short-term adverse events (including dysphagia, heartburn, regurgitation et al.) between the two groups (P = 0.157). At the time of the latest follow-up, there was no difference in the incidence of symptomatic reflux symptom (heartburn and regurgitation) between the two groups (heartburn: P = 0.363; regurgitation: P = 1.000). A higher frequency of dysphagia was present in the LNF group compared with the LTF group (P = 0.023). DISCUSSION: LNF is associated with an excessive elevation of LESP which may lead to further persistent dysphagia. Partial fundoplication may provide adequate reflux control, improve esophageal body motility and minimize complications associated with an 'over-tight' fundal wrap. CONCLUSION: LTF seems to be as safe and effective on the long-term as LNF, but with a lower incidence of postoperative dysphagia (ChiCTR-TRC-13003945). PMID- 26360741 TI - The association effect of quaternary ammonium salt on carboxymethyl cellulose and its analytical applications. AB - Sodium carboxymethyl cellulose (CMC) has been extensively used in petroleum, geology, common household chemicals, food, medicine and other industries, owing to its excellent water-soluble, emulsifying, water retention and film forming properties. It is known as 'industrial monosodium glutamate'. However, the research of the test method on CMC is far behind the research of its actual application value. This study showed that, weak acid or weak basic medium, the carboxyl groups dissociated from CMC, existing as a big negative ion, which can form ion-association complexes with some quaternary ammonium cations through electrostatic and hydrophobic interactions. The absorption spectrum changes and Triton-X100 can increase the sensitivity of the system. The maximum absorption wavelengths are, respectively, about 256 nm for dodecyl trimethyl ammonium bromide (LTAB), 244 nm for tetradecyltrimethyl ammonium bromide (TTAB) and 240 nm for cetyltrimethyl ammonium bromide (CTAB) with CMC. The reactions show very high sensitivities and the maximum molar absorption coefficients are 1.10 * 10(4) L/(mol.cm) for LTAB system, 1.24 * 10(6) L/(mol.cm) for TTAB system and 1.78 * 10(6) L/(mol.cm) for CTAB system. This method is simple and rapid, and can be applied for the spectrophotometric determination of trace CMC in the supernatant of centrifuged drilling mud. PMID- 26360742 TI - Proteins causing membrane fouling in membrane bioreactors. AB - In this study, the details of proteins causing membrane fouling in membrane bioreactors (MBRs) treating real municipal wastewater were investigated. Two separate pilot-scale MBRs were continuously operated under significantly different operating conditions; one MBR was a submerged type whereas the other was a side-stream type. The submerged and side-stream MBRs were operated for 20 and 10 days, respectively. At the end of continuous operation, the foulants were extracted from the fouled membranes. The proteins contained in the extracted foulants were enriched by using the combination of crude concentration with an ultrafiltration membrane and trichloroacetic acid precipitation, and then separated by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE). The N terminal amino acid sequencing analysis of the proteins which formed intensive spots on the 2D-PAGE gels allowed us to partially identify one protein (OmpA family protein originated from genus Brevundimonas or Riemerella anatipestifer) from the foulant obtained from the submerged MBR, and two proteins (OprD and OprF originated from genus Pseudomonas) from that obtained from the side-stream MBR. Despite the significant difference in operating conditions of the two MBRs, all proteins identified in this study belong to beta-barrel protein. These findings strongly suggest the importance of beta-barrel proteins in developing membrane fouling in MBRs. PMID- 26360743 TI - Applicability of an electrochemical Fenton-type process to actual wastewater treatment. AB - The applicability of an electrochemical Fenton-type process (EF-HOCl-ReFe) to the treatment of three actual wastewaters, namely wastewater from an automobile factory (automobile wastewater), metal scrap-cleansing wastewater, and municipal wastewater, is discussed in this research. The EF-HOCl-ReFe successfully removed the chemical oxygen demand (COD) from automobile wastewater pre-treated by a coagulation process without any inhibition. The apparent current efficiency reached 86%, 46% of which was ascribed to the electrochemical Fenton-type mechanism. The metal scrap-cleansing wastewater had a yellow colour and high concentrations of COD (6550 mg/L) and Cl(-) (1560 mM). The EF-HOCl-ReFe could achieve almost complete COD removal and decolourization after 48 h of treatment, although a temporary intensification of colour was observed before the decolourization. The EF-HOCl-ReFe was also effective in the removal of 1,4 dioxane from municipal wastewater pre-treated by activated sludge and coagulation processes, which were unable to remove 1,4-dioxane. The 1,4-dioxane removal efficiency after 30 min of treatment reached 68.5%. Thus, the EF-HOCl-ReFe was applicable to the treatment of these actual wastewaters. PMID- 26360744 TI - Would a two-stage N-removal be a suitable technology to implement at full scale the use of anammox for sewage treatment? AB - Sewage treatment with anammox could be implemented through a two-step reactor system, where the first reactor would be devoted to partial nitritation. A process design was sketched including control loops. The control strategy regulates the flow-rate of the rich ammonium sidestream produced after dewatering the digested sludge, to keep the ammonium concentration at a set point in the partial nitritation reactor by DOsing the SIde Stream (DOSIS). A second control loop manages the ammonium concentration set point based on the measurement of the total nitrogen in the partial nitritation reactor. A mathematical model was developed to assess the amount of sidestream required. Even in the case of a strong diurnal variability, simulations show how the control strategy is correctly performing, demonstrating the potential of the proposed technology. PMID- 26360745 TI - Biosorption of Congo Red from aqueous solution by Bacillus weihenstephanensis RI12; effect of SPB1 biosurfactant addition on biodecolorization potency. AB - Bacillus weihenstephanensis RI12, isolated from hydrocarbon contaminated soil, was assessed for Congo Red bio-treatment potency. Results suggested the potential of this bacterium for use in effective treatment of Congo Red contaminated wastewaters under shaking conditions at acidic and neutral pH value. The strain could tolerate higher doses of dyes as it could decolorize up to 1,000 mg/l of Congo Red. When used as microbial surfactant to enhance Congo Red biodecolorization, Bacillus subtilis SPB1-derived lipopeptide accelerated the decolorization rate and maximized the decolorization efficiency at an optimal concentration of biosurfactant of about 0.075%. Studies ensured that Congo Red removal by this strain could be due to an adsorption phenomena. Germination potencies of tomato seeds using the treated dyes under different conditions showed the efficient biotreatment of the azo dye Congo Red especially with the addition of SPB1 biosurfactant. To conclude, the addition of SPB1 bioemulsifier reduced energy costs by reducing the effective decolorization period; the biosurfactant stimulated bacterial decolorization method may provide a highly efficient, inexpensive and time-saving procedure in the treatment of textile effluents. PMID- 26360746 TI - Performance of sulphate- and selenium-reducing biochemical reactors using different ratios of labile to recalcitrant organic materials. AB - Successful operation of sulphate-reducing bioreactors using complex organic materials depends on providing a balance between more easily degrading material that achieves reasonable kinetics and low hydraulic retention times, and more slowly decomposing material that sustains performance in the long term. In this study, two organic mixtures containing the same ingredients typical of bioreactors used at mine sites (woodchips, hay and cow manure) but with different ratios of wood (recalcitrant) to hay (labile) were tested in six continuous flow bioreactors treating synthetic mine-affected water containing 600 mg/L of sulphate and 15 MUg/L of selenium. The reactors were operated for short (5-6 months) and long (435-450 days) periods of time at the same hydraulic retention time of 15 days. There were no differences in the performance of the bioreactors in terms of sulphate-reduction over the short term, but the wood-rich bioreactors experienced variable and sometimes unreliable sulphate-reduction over the long term. Presence of more hay in the organic mixture was able to better sustain reliable performance. Production of dissolved organic compounds due to biodegradation within the bioreactors was detected for the first 175-230 days, after which their depletion coincided with a crash phase observed in the wood rich bioreactors only. PMID- 26360747 TI - Proteomics reliability for micropollutants degradation insight into activated sludge systems. AB - Little information is available on pharmaceutical trace compounds degradation pathways in wastewater. The potential of the proteomics approach has been evaluated to extract information on activated sludge microbial metabolism in degrading a trace concentration of a pharmaceutical compound (ibuprofen). Ibuprofen is one of the most consumed pharmaceuticals, measured in wastewater at very high concentrations and, despite its high removal rates, found in different environmental compartments. Aerated and completely mixed activated sludge batch tests were spiked with ibuprofen at 10 and 1,000 MUg L(-1). Ibuprofen concentrations were determined in the liquid phase: 100% removal was observed and the kinetics were estimated. The solid phase was sampled for proteomics purposes. The first objective was to apply proteomics to evaluate protein profile variations in a complex matrix such as activated sludge. The second objective was to determine, at different ibuprofen concentrations, which proteins followed pre defined trends. No newly expressed proteins were found. Nonetheless, the obtained results suggest that proteomics itself is a promising methodology to be applied in this field. Statistical and comparative studies analyses provided, in fact, useful information on biological reproducibility and permitted us to detect 62 proteins following coherent and plausible expected trends in terms of presence and intensity change. PMID- 26360748 TI - A novel poly(acrylic acid-co-acrylamide)/diatomite composite flocculant with outstanding flocculation performance. AB - Series of anionic flocculants with outstanding flocculation performance, poly(acrylic acid-co-acrylamide)/diatomite composite flocculants (PAAD) were successfully prepared through aqueous solution copolymerization and applied to flocculate from oil-field fracturing waste-water. The structure of PAAD was characterized by Fourier transform infra-red spectroscopy, (13)C nuclear magnetic resonance and X-ray diffraction tests, and its properties were systematically evaluated by viscometer, thermogravimetry analysis and flocculation measurements. Furthermore, the influences of various reaction parameters on the apparent viscosity of flocculant solution were studied, and the optimum synthesis condition was determined. The novel composite flocculants exhibited outstanding flocculation properties. Specifically, the dosage of composite flocculants that could make the transmittance of treated wastewater exceed 90% was only approximately 12-35 ppm, which was far lower than that of conventional flocculants. Meanwhile, the settling time was lower than 5 s, which was similar to that of conventional flocculants. This was because PAAD flocculants had a higher absorption capacity, and larger chain extending space than conventional linear flocculants, which could refrain from the entanglement of linear polymer chains and significantly improve flocculation capacity. PMID- 26360749 TI - Parametric and adsorption kinetic studies of methylene blue removal from simulated textile water using durian (Durio zibethinus murray) skin. AB - In this study, durian (Durio zibethinus Murray) skin was examined for its ability to remove methylene blue (MB) dye from simulated textile wastewater. Adsorption equilibrium and kinetics of MB removal from aqueous solutions at different parametric conditions such as different initial concentrations (2-10 mg/L), biosorbent dosages (0.3-0.7 g) and pH solution (4-9) onto durian skin were studied using batch adsorption. The amount of MB adsorbed increased from 3.45 to 17.31 mg/g with the increase in initial concentration of MB dye; whereas biosorbent dosage increased from 1.08 to 2.47 mg/g. Maximum dye adsorption capacity of the durian skin was found to increase from 3.78 to 6.40 mg/g, with increasing solution pH. Equilibrium isotherm data were analyzed according to Langmuir and Freundlich isotherm models. The sorption equilibrium was best described by the Freundlich isotherm model with maximum adsorption capacity of 7.23 mg/g and this was due to the heterogeneous nature of the durian skin surface. Kinetic studies indicated that the sorption of MB dye tended to follow the pseudo second-order kinetic model with promising correlation of 0.9836 < R(2) < 0.9918. PMID- 26360750 TI - Recycling of coal seam gas-associated water using vacuum membrane distillation. AB - Coal seam gas-associated water (CSGAW), which is a by-product of coal seam gas (CSG) production typically contains significant amounts of salts and has potential environmental issues. In this study, we optimized a bench-scale vacuum membrane distillation (VMD) process with flat-sheet hydrophobic polytetrafluoroethylene (PTFE) membranes for the treatment of synthetic CSGAW (conductivity = 15 mS/cm). To study performance of the VMD process, we explored the effects of feed temperature (T(f) = 60, 70, and 80 degrees C), feed flow rate (V(f) = 60, 120, and 240 mL/min), and vacuum pressure (P(v) = 3, 6, and 9 kPa) on water permeability through the PTFE membrane in the VMD process. Under the optimum conditions (i.e. T(f) = 80 degrees C, V(f) = 240 mL/min, P(v) = 3 kPa), water permeability and rejection efficiency of salts by the VMD process were found to be 5.5 L/m(2)/h (LMH) and 99.9%, respectively, after 2 h filtration. However, after 8 h operation, the water permeability decreased by 70% compared with the initial flux due to the formation of fouling layer of calcium, chloride, sodium, magnesium, and potassium on the membrane surface. PMID- 26360751 TI - Performance evaluation of a novel reciprocation membrane bioreactor (rMBR) for enhanced nutrient removal in wastewater treatment: a comparative study. AB - This study compared and evaluated the performance of a conventional membrane bioreactor (MBR) and a novel reciprocation MBR (rMBR) which used mechanical membrane reciprocation in place of membrane air scouring in pilot-scale tests. Each system was independently operated for 280 days at a local wastewater treatment plant for a parallel assessment of operating performance. The rMBR was found to be more effective than the MBR with regard to operating performance and energy consumption. Inertial forces created by the reciprocating motion shook foulants from the membrane surface. In addition, because of the looseness of the fibers, they moved relative to each other during reciprocation thus preventing sludge clogging inside the fiber bundle. Because the rMBR does not use aeration for membrane cleaning, the membrane tank in the rMBR maintained anoxic conditions, allowing endogenous denitrification in the membrane tank. The rMBR permeate contained an average of 1.7 mg/L total nitrogen (TN) with less than 1 mg/L NO(3)-N, while the TN concentration in the MBR permeate averaged 5 mg/L with 3.5 mg/L NO(3)-N. The specific energy consumption for membrane reciprocation in the rMBR was 0.064 kWh/m(3), while that for air scouring in the MBR was 0.19 kWh/m(3). PMID- 26360752 TI - Modeling of coastal water contamination in Fortaleza (Northeastern Brazil). AB - An important tool in environmental management projects and studies due to the complexity of environmental systems, environmental modeling makes it possible to integrate many variables and processes, thereby providing a dynamic view of systems. In this study the bacteriological quality of the coastal waters of Fortaleza (a state capital in Northeastern Brazil) was modeled considering multiple contamination sources. Using the software SisBaHiA, the dispersion of thermotolerant coliforms and Escherichia coli from three sources of contamination (local rivers, storm drains and submarine outfall) was analyzed. The models took into account variations in bacterial decay due to solar radiation and other environmental factors. Fecal pollution discharged from rivers and storm drains is transported westward by coastal currents, contaminating strips of beach water to the left of each storm drain or river. Exception to this condition only occurs on beaches protected by the breakwater of the harbor, where counterclockwise vortexes reverse this behavior. The results of the models were consistent with field measurements taken during the dry and the rainy season. Our results show that the submarine outfall plume was over 2 km from the nearest beach. The storm drains and the Maceio stream are the main factors responsible for the poor water quality on the waterfront of Fortaleza. The depollution of these sources would generate considerable social, health and economic gains for the region. PMID- 26360753 TI - Evaluation of thermal steam-explosion key operation factors to optimize biogas production from biological sludge. AB - Thermal steam-explosion is the most extended hydrolysis pretreatment to enhance anaerobic digestion of sludge. Thermal hydrolysis key parameters are temperature (T) and time (t), and the generally accepted values reported from full-scale information are: 150-230 degrees C and 20-60 min. This study assesses the influence of different temperature-time-flash combinations (110-180 degrees C, 5 60 min, 1-3 re-flashing) on the anaerobic degradation of secondary sludge through biochemical methane potential (BMP) tests. All the conditions tested presented higher methane production compared to the untreated sludge, and both solubilization (after the hydrolysis) and degradation (by anaerobic digestion) increased linearly when increasing the severity (T-t) of the pretreatment, reaching 40% solubilization and degradation of the particulate matter at 180 degrees C-60 min. However, for the 180 degrees C temperature, the treatment time impacted negatively on the lag phase. No influence of re-flashing the pretreated matter was observed. In conclusion, thermal steam-explosion at short operation times (5 min) and moderate temperatures (145 degrees C) seems to be very attractive from a degradation point of view thus presenting a methane production enhancement similar to the one obtained at 180 degrees C and without negative influence of the lag phase. PMID- 26360754 TI - Removal of Ni(II) from aqueous solution by using micellar enhanced ultrafiltration. AB - To explore the potential of micellar enhanced ultrafiltration (MEUF) process for the treatment of industrial effluent, herein, we report the surfactant-based separation of a metal ion [Ni(II)] from the aqueous solution using two different anionic surfactants viz. dioctyl sodium sulfosuccinate (DSS) and sodium dodecyl sulfate (SDS). By following a systematic investigation, we utilized two membranes with different pore sizes viz. 10,000 MWCO (molecular weight cutoff) and 30,000 MWCO and determined the rejection coefficient and permeate flux of the Ni(II) from aqueous at 1.5 bar trans-membrane pressure. The experimental results showed higher percentage of Ni(II) retention upon using the micellar solution of SDS compared with the solution containing DSS surfactant. In addition, the retention of Ni(II) ions incorporated in the micelles of surfactants was also found to be higher upon using 10,000 MWCO membrane compared with 30,000 MWCO membrane. Hence, we suggest that the combination of SDS surfactant and 10,000 MWCO membrane is a potent solution for the removal of metal ions from aqueous solutions via MEUF process. PMID- 26360755 TI - Determination of number of check dams by artificial neural networks in arid regions of Iran. AB - An artificial neural network (ANN) model with six hydrological factors including time of concentration (TC), curve number, slope, imperviousness, area and input discharge as input parameters and number of check dams (NCD) as output parameters was developed and created using GIS and field surveys. The performance of this model was assessed by the coefficient of determination R(2), root mean square error (RMSE), values account and mean absolute error (MAE). The results showed that the computed values of NCD using ANN with a multi-layer perceptron (MLP) model regarding RMSE, MAE, values adjustment factor (VAF), and R(2) (1.75, 1.25, 90.74, and 0.97) for training, (1.34, 0.89, 97.52, and 0.99) for validation and (0.53, 0.8, 98.32, and 0.99) for test stage, respectively, were in close agreement with their respective values in the watershed. Finally, the sensitivity analysis showed that the area, TC and curve number were the most effective parameters in estimating the number of check dams. PMID- 26360756 TI - Reduction of concentrated nitrate by using in situ synthesized zero-valent copper. AB - Although zero-valent iron represents a promising approach for reduction of nitrate (NO(3)(-)) in water, its application in concentrated nitrate is limited by surface passivation. In this study, an alternative approach using in situ synthesized zero-valent copper (Cu(0)) produced by borohydride (NaBH(4)) was investigated. Complete reduction was observed within 55 min by reacting 677 mg N/L of NO(3)(-) with CuO (0.312 g/L) and NaBH(4) (4.16 g/L) at 60 degrees C. The pseudo-first-order rate constant was 0.059 min(-1), and it increased threefold when the CuO dose was increased to 1.24 g/L. Increasing the NaBH(4) dose produced less nitrite (NO(2)(-)) throughout the experiments, indicating that it is the primary agent for reducing NO(2)(-). The initial pH exerted a significant effect on the reaction rate, and NO(3)(-) was rapidly reduced when the initial pH was less than 4. Based on the research findings, possible reaction pathways for NO(3)(-) reduction by Cu(0) are proposed in this work. PMID- 26360757 TI - Enhanced anaerobic digestion of waste activated sludge of low organic content in a novel digester. AB - A novel digester, termed an internal circulation anaerobic digester (ICAD), was developed to intensify sludge digestion. It consists of reaction zone, settling zone, thickening zone, riser and downcomer. Internal circulation in the digester is intensified by backflow biogas. The mesophilic ICAD treating thermal pretreated waste activated sludge with volatile suspended solids (VSS)/suspended solids (SS) of 0.45-0.49 was conducted in this study to reduce and stabilize the low organic content sludge. The results showed that the VSS removal rate and biogas rate reached 46.0% and 0.72 m(3)/kg VSS(fed) at hydraulic retention time (HRT) of 15 days. VSS/SS and soluble chemical oxygen demand (SCOD) of the effluent sludge ranged from 0.39 to 0.41 and 274 mg/L to 473 mg/L, respectively, under various HRTs from 10 to 27 days. The degradation ability of ICAD derived from the improved mass transfer by internal circulation and long solid retention time at short HRT is compared with continuous stirred tank reactor. PMID- 26360758 TI - Partial carbonized nanoporous resin for uptake of lead from aqueous solution. AB - Four partial carbonized nanoporous resins (PCNRs), based on organic xerogel compounds, were synthesised by the sol-gel method from pyrogallol and formaldehyde mixtures in water using picric acid as catalyst. The PCNRs were prepared at different pyrolysis temperatures: T(1) = 200 degrees C (PF-200), T(2) = 300 degrees C (PF-300), T(3) = 400 degrees C (PF-400), or T(4) = 500 degrees C (PF-500). The PCNRs were characterized by scanning electron microscopy, transmission electron microscopy, X-ray diffraction, Fourier transformed infrared spectroscopy, and nitrogen porosimetry. The obtained results show that PF-200 is more efficient for the removal of Pb(2+) from aqueous solution than the other adsorbent prepared in this study. The characteristics of lead uptake by PF-200 were explored using well-established and effective parameters including pH, contact time, initial metal ion concentration and temperature. Optimum adsorption of Pb(2+), using PF-200, was observed at pH 4.5. The Langmuir model gave a better fit than the other models, and kinetic studies revealed that the adsorption was well fitted by the pseudo second-order kinetic model and thermodynamic properties, i.e., Gibbs free energy change, enthalpy change and entropy change, showed that adsorption of Pb(2+) onto PF-200 was endothermic, spontaneous and feasible in the temperature range of 298-328 K. PMID- 26360759 TI - Removal of Pb(II) by adsorption onto Chinese walnut shell activated carbon. AB - The excessive discharge of Pb(II) into the environment has increasingly aroused great concern. Adsorption is considered as the most effective method for heavy metal removal. Chinese walnut shell activated carbon (CWSAC) was used as an adsorbent for the removal of Pb(II) from aqueous solution. Batch experiments were conducted by varying contact time, temperature, pH, adsorbent dose and initial Pb(II) concentration. Adsorption equilibrium was established within 150 min. Although temperature effect was insignificant, the Pb(II) adsorption was strongly pH dependent and the maximum removal was observed at pH 5.5. The Pb(II) removal efficiency increased with increasing CWSAC dosage up to 2.0 g/L and reached a maximum of 94.12%. Langmuir and Freundlich adsorption isotherms were employed to fit the adsorption data. The results suggested that the equilibrium data could be well described by the Langmuir isotherm model, with a maximum adsorption capacity of 81.96 mg/g. Adsorption kinetics data were fitted by pseudo-first- and pseudo second-order models. The result indicated that the pseudo-first-order model best describes the adsorption kinetic data. In summary, CWSAC could be a promising material for the removal of Pb(II) from wastewater. PMID- 26360760 TI - 454 pyrosequencing-based characterization of the bacterial consortia in a well established nitrifying reactor. AB - This present study aimed to characterize the bacterial community in a well established nitrifying reactor by high-throughput sequencing of 16S rRNA amplicons. The laboratory-scale continuous stirred tank reactor has been supplied with ammonium (NH(4)(+)) as sole energy source for over 5 years, while no organic carbon has been added, assembling thus a unique planktonic community with a mean NH(4)(+) removal rate of 86 +/- 1.4 mg NH(4)(+)-N/(L d). Results showed a nitrifying community composed of bacteria belonging to Nitrosomonas (relative abundance 11.0%) as the sole ammonia oxidizers (AOB) and Nitrobacter (9.3%) as the sole nitrite oxidizers (NOB). The Alphaproteobacteria (42.3% including Nitrobacter) were the most abundant class within the Proteobacteria (62.8%) followed by the Gammaproteobacteria (9.4%). However, the Betaproteobacteria (excluding AOB) contributed only 0.08%, confirming that Alpha- and Gammaproteobacteria thrived in low-organic-load environments while heterotrophic Betaproteobacteria are not well adapted to these conditions. Bacteroidetes, known to metabolize extracellular polymeric substances produced by nitrifying bacteria and secondary metabolites of the decayed biomass, was the second most abundant phylum (30.8%). It was found that Nitrosomonas and Nitrobacter sustained a broad population of heterotrophs in the reactor dominated by Alpha- and Gammaproteobacteria and Bacteroidetes, in a 1:4 ratio of total nitrifiers to all heterotrophs. PMID- 26360761 TI - The urban harvest approach as framework and planning tool for improved water and resource cycles. AB - Water and resource availability in sufficient quantity and quality for anthropogenic needs represents one of the main challenges in the coming decades. To prepare for upcoming challenges such as increased urbanization and climate change related consequences, innovative and improved resource management concepts are indispensable. In recent years we have developed and applied the urban harvest approach (UHA). The UHA aims to model and quantify the urban water cycle on different temporal and spatial scales. This approach allowed us to quantify the impact of the implementation of water saving measures and new water treatment concepts in cities. In this paper we will introduce the UHA and its application for urban water cycles. Furthermore, we will show first results for an extension to energy cycles and highlight future research items (e.g. nutrients, water energy-nexus). PMID- 26360762 TI - Energy audit in small wastewater treatment plants: methodology, energy consumption indicators, and lessons learned. AB - Energy audits in wastewater treatment plants (WWTPs) reveal large differences in the energy consumption in the various stages, depending also on the indicators used in the audits. This work is aimed at formulating a suitable methodology to perform audits in WWTPs and identifying the most suitable key energy consumption indicators for comparison among different plants and benchmarking. Hydraulic based stages, stages based on chemical oxygen demand, sludge-based stages and building stages were distinguished in WWTPs and analysed with different energy indicators. Detailed energy audits were carried out on five small WWTPs treating less than 10,000 population equivalent and using continuous data for 2 years. The plants have in common a low designed capacity utilization (52% on average) and equipment oversizing which leads to waste of energy in the absence of controls and inverters (a common situation in small plants). The study confirms that there are several opportunities for reducing energy consumption in small WWTPs: in addition to the pumping of influent wastewater and aeration, small plants demonstrate low energy efficiency in recirculation of settled sludge and in aerobic stabilization. Denitrification above 75% is ensured through intermittent aeration and without recirculation of mixed liquor. Automation in place of manual controls is mandatory in illumination and electrical heating. PMID- 26360763 TI - Effects of the incorporation of drinking water sludge on the anaerobic digestion of domestic wastewater sludge for methane production. AB - Water purification and wastewater treatment generate sludge, which must be adequately handled to prevent detrimental effects to the environment and public health. In this study, we examined the influence of the application of settled sludge from a drinking water treatment plant (S(DWTP)) on the anaerobic digestion (AD) of the thickened primary sludge from a municipal wastewater treatment plant (S(WWTP)) which uses chemically assisted primary treatment (CAPT). On both plants the primary coagulant is ferric chloride. The study was performed at laboratory scale using specific methanogenic activity (SMA) tests, in which mixtures of S(WWTP)-S(DWTP) with the ratios 100:00, 80:20, 75:25, 70:30 and 00:100 were evaluated. Methane detection was also performed by gas chromatography for a period of 30 days. Our results show that all evaluated ratios that incorporate S(DWTP), produce an inhibitory effect on the production of methane. The reduction in methane production ranged from 26% for the smallest concentration of S(DWTP) (20%) to more than 70% for concentrations higher than 25%. The results indicated that the hydrolytic stage was significantly affected, with the hydrolysis constant Kh also reduced by approximately 70% (0.24-0.26 day(-1) for the different ratios compared with 0.34 day(-1) for the S(WWTP) alone). This finding demonstrates that the best mixtures to be considered for anaerobic co-digestion must contain a fraction of S(DWTP) below 20%. PMID- 26360764 TI - Effect of salinity on the toxicity of road dust in an estuarine amphipod Grandidierella japonica. AB - Urban runoff can reach coastal aquatic environments; however, little is known about the effect of salinity on road runoff toxicity. The objective of this study is to investigate the toxicity of highway road dust over a salinity gradient from 5 to 350/00, in an estuarine benthic amphipod, Grandidierella japonica. Road dust toxicity was evaluated by assessing mortality after 10 days of exposure and short term microbead ingestion activity of the amphipod. For all road dust samples considered, amphipod mortality increased with increasing salinity, whereas no significant difference in mortality was observed among test salinities in the reference river sediment. Ingestion activity during exposure to road dust decreased with increasing salinity. In fact, none of the individuals ingested any microbeads at salinity of 350/00. If assumed microbead ingestion is a proxy for feeding activity, high mortality at 350/00 could be attributed to aquatic exposure and not to dietary exposure. These findings suggest that road dust may have considerable impact on benthic organisms at high salinity levels. PMID- 26360765 TI - Modeling of wastewater quality in an urban area during festival and rainy days. AB - Water pollution during festival periods is a major problem in all festival cities across the world. Reliable prediction of water pollution is essential in festival cities for sewer and wastewater management in order to ensure public health and a clean environment. This article aims to model the biological oxygen demand (BOD(5)), and total suspended solids (TSS) parameters in wastewater in the sewer networks of Karbala city center during festival and rainy days using structural equation modeling and multiple linear regression analysis methods. For this purpose, 34 years (1980-2014) of rainfall, temperature and sewer flow data during festival periods in the study area were collected, processed, and employed. The results show that the TSS concentration increases by 26-46 mg/l while BOD(5) concentration rises by 9-19 mg/l for an increase of rainfall by 1 mm during festival periods. It was also found that BOD(5) concentration rises by 4-17 mg/l for each increase of 10,000 population. PMID- 26360767 TI - The decays of (109,111)Pd and (111)Ag following neutron capture by Pd. AB - Improved precisions of the energies and intensities of the gamma rays emitted in the decays of (109)Pd and (111g,m)Pd have been obtained based on a high resolution spectroscopic study of these gamma emissions from radioactive samples produced by neutron capture by natural Pd. Correspondingly improved values of the energies and beta feedings of the levels in the (109,)(111)Ag daughters have been deduced. More precise energies and intensities have also been determined for the gamma rays emitted in the decays of the (111)Pd daughter activities (111g,m)Ag to (111)Cd. PMID- 26360766 TI - Synergistic Effect of Oleanolic Acid on Aminoglycoside Antibiotics against Acinetobacter baumannii. AB - Difficulties involved in treating drug-resistant pathogens have created a need for new therapies. In this study, we investigated the possibility of using oleanolic acid (OA), a natural pentacyclic triterpenoid, as a natural adjuvant for antibiotics against Acinetobacter baumannii. High concentrations of OA can kill cells, partly because it generates reactive oxygen species. Measurement of the fractional inhibitory concentration (FIC) for OA and time-kill experiments demonstrated that it only synergizes with aminoglycoside antibiotics (e.g., gentamicin, kanamycin). Other classes of antibiotics (e.g., ampicillin, rifampicin, norfloxacin, chloramphenicol, and tetracycline) have no interactions with OA. Microarray and quantitative reverse transcription-PCR analysis indicated that genes involved in ATP synthesis and cell membrane permeability, the gene encoding glycosyltransferase, peptidoglycan-related genes, phage-related genes, and DNA repair genes were upregulated under OA. OA highly induces the expression of adk, which encodes an adenylate kinase, and des6, which encodes a linoleoyl CoA desaturase, and deletion of these genes increased FICs; these observations indicate that adk and des6 are involved in the synergism of OA with aminoglycosides. Data obtained using 8-anilino-1-naphthalenesulfonic acid, fluorescence-conjugated gentamicin, and membrane fatty acid analysis indicates that adk and des6 are involved in changes in membrane permeability. Proton-motive force and ATP synthesis tests show that those genes are also involved in energy metabolism. Taken together, our data show that OA boosts aminoglycoside uptake by changing membrane permeability and energy metabolism in A. baumannii. PMID- 26360768 TI - Is There a Benefit to Head Size Greater Than 36 mm in Total Hip Arthroplasty? AB - This study compares the rate of dislocation and revision for instability between 36-mm and anatomic femoral heads (large diameter metal-on-metal THA, dual mobility bearings, and hip resurfacing arthroplasty) in patients at high risk for dislocation. A total of 501 high-risk patients, over a 10-year period, were identified (282 36-mm THA, 24 dual-mobility bearings, 83 metal-on-metal arthroplasty, and 112 hip resurfacing arthroplasty). There were 13 dislocations in the 36-mm group compared to 1 in the anatomic group (4.6% vs 0.5%; P = .005). Four patients dislocated more than once in the 36-mm group (1.4% vs 0%; P = .04), and 2 patients in the 36-mm group required a revision for instability (0.7% vs 0%; P = .11). These results suggest that anatomic head sizes significantly lower the risk of dislocation in high-risk patients. PMID- 26360769 TI - Multi-region to single region shear thinning transitions in drying PEDOT:PSS dispersions: contributions from charge density fluctuations. AB - The multiple shear thinning behaviour observed in dispersions of the conducting polymer, poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) ( PEDOT: PSS), in water during the drying process is explored. PEDOT: PSS dispersions in water can be non-stoichiometric polyelectrolyte complexes (PECs) with free polyanion (PSS) chains resulting in scrambled egg conformations. They also behave as charged colloidal particles. The behaviour of PEDOT: PSS dispersions as PECs and charged colloidal systems during drying is analyzed using rheology and TEM, zeta potential, conductivity, pH, dynamic light scattering (DLS) and rheo-small angle light scattering (rheo-SALS) information. The rheological behaviour is found to have significant contributions from conformational changes in the PEDOT: PSS PEC due to charge density fluctuations affecting the electrostatic persistence length, le. A low concentration regime with multiple shear thinning behaviour and a high concentration regime with single shear thinning behaviour were observed. The PEC behavior of PEDOT: PSS is further explored by charge neutralizing the dispersions with salts. PMID- 26360771 TI - Europium triple-decker complexes containing phthalocyanine and nitrophenyl corrole macrocycles. AB - A series of europium triple-decker complexes containing phthalocyanine and nitrophenyl-corrole macrocycles were synthesized and characterized by spectroscopic and electrochemical methods in nonaqueous media. The examined compounds are represented as Eu2[Pc(OC4H9)8]2[Cor(Ph)n(NO2Ph)3-n], where n varies from 0 to 3, Pc(OC4H9)8 represents the phthalocyanine macrocycle, and Cor indicates the corrole macrocycle having phenyl (Ph) or nitrophenyl (NO2Ph) meso substituents. Three different methods were used for syntheses of the target complexes, two of which are reported here for the first time. Each examined compound undergoes five reversible one-electron oxidations and 3-5 one-electron reductions depending upon the number of NO2Ph substituents. The nitrophenyl groups on the meso positions of the corrole are highly electron-withdrawing, and this leads to a substantial positive shift in potential for the five oxidations and first reduction in CH2Cl2, PhCN, or pyridine as compared to the parent triple decker compound with a triphenylcorrole macrocycle. The measured E1/2 values are linearly related to the number of NO2Ph groups on the corrole, and the relative magnitude of the shift in potential for each redox reaction was used in conjunction with the results from thin-layer spectro-electrochemistry to assign the initial site of oxidation or reduction on the molecule. The nitrophenyl substituents are also redox-active, and each is reduced to [C6H4NO2](-) in a separate one-electron transfer step at potentials between -1.12 and -1.42 V versus saturated calomel electrode. PMID- 26360772 TI - Operational assessment of the 5-h on/10-h off watchstanding schedule on a US Navy ship: sleep patterns, mood and psychomotor vigilance performance of crewmembers in the nuclear reactor department. AB - We assessed sleep patterns, psychomotor vigilance performance, work demands and mood of 77 crewmembers of USS NIMITZ (CVN-68) on the rotating 5-h on/10-h off (5/10) watchstanding schedule. Within the 3-day cycle of the 5/10, sleep occurred at distinctly different times each day. On two of these days, sailors typically received only brief, 4-h sleep episodes followed by periods of sustained wakefulness (approximately 22 and 20 h). Crewmembers received approximately seven hours of sleep daily, but reported excessive fatigue and dissatisfaction with their schedule. Crewmembers' mood worsened significantly over the course of the underway phase. Psychomotor vigilance performance (reaction times, lapses) was significantly degraded compared to performance when working circadian-aligned schedules. Overall, standing watch on the 5/10 schedule, combined with other work duties, resulted in poor sleep hygiene. Crewmembers on the 5/10 experienced periodic bouts of sustained wakefulness and accrued a significant sleep debt due to extended workdays and circadian-misaligned sleep. Practitioner summary: We assessed crewmembers' sleep patterns, psychomotor vigilance performance and work demands when working a rotating 5-h on/10-h off (5/10) watchstanding schedule. The 5/10, combined with other work duties, resulted in poor sleep hygiene. Crewmembers experienced periodic bouts of sustained wakefulness and accrued a significant sleep debt due to extended workdays and circadian-misaligned sleep. PMID- 26360770 TI - Trait sensitivity to social disconnection enhances pro-inflammatory responses to a randomized controlled trial of endotoxin. AB - One proposed mechanism for the association between social isolation and poor health outcomes is inflammation. Lonely or socially disconnected individuals show greater inflammatory responses, including up-regulation of pro-inflammatory gene expression, and people who are sensitive to cues of social disconnection (e.g., high levels of anxious attachment) exhibit greater inflammation in response to psychological stress. However, no studies have examined how sensitivity to social disconnection may influence pro-inflammatory responses to an inflammatory challenge. In the present study, we investigated the impact of sensitivity to social disconnection (a composite score comprised of loneliness, anxious attachment, fear of negative evaluation, and rejection sensitivity) on pro inflammatory cytokines and gene expression in response to endotoxin, an inflammatory challenge, vs. placebo in a sample of one hundred and fifteen (n=115) healthy participants. Results showed that those who are more sensitive to social disconnection show increased pro-inflammatory responses (i.e., increased levels of tumor necrosis factor-alpha and interleukin-6) to endotoxin, as well as up-regulation of multiple genes related to inflammation. Furthermore, bioinformatics analyses revealed that those in the endotoxin group who are more sensitive to social disconnection exhibited a conserved transcriptional response to adversity (CTRA) regulatory profile, involving up-regulation of beta adrenergic and pro-inflammatory transcription control pathways and down regulation of antiviral transcription factors in response to endotoxin. These results may ultimately have implications for understanding the links between social isolation, inflammation, and health. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov NCT01671150. PMID- 26360773 TI - Incidence of Inadvertent Intraoperative Hypothermia and Its Risk Factors in Patients Undergoing General Anesthesia in Beijing: A Prospective Regional Survey. AB - BACKGROUND/OBJECTIVE: Inadvertent intraoperative hypothermia (core temperature <360 C) is a recognized risk in surgery and has adverse consequences. However, no data about this complication in China are available. Our study aimed to determine the incidence of inadvertent intraoperative hypothermia and its associated risk factors in a sample of Chinese patients. METHODS: We conducted a regional cross sectional survey in Beijing from August through December, 2013. Eight hundred thirty patients who underwent various operations under general anesthesia were randomly selected from 24 hospitals through a multistage probability sampling. Multivariate logistic regression analyses were applied to explore the risk factors of developing hypothermia. RESULTS: The overall incidence of intraoperative hypothermia was high, 39.9%. All patients were warmed passively with surgical sheets or cotton blankets, whereas only 10.7% of patients received active warming with space heaters or electric blankets. Pre-warmed intravenous fluid were administered to 16.9% of patients, and 34.6% of patients had irrigation of wounds with pre-warmed fluid. Active warming (OR = 0.46, 95% CI 0.26-0.81), overweight or obesity (OR = 0.39, 95% CI 0.28-0.56), high baseline core temperature before anesthesia (OR = 0.08, 95% CI 0.04-0.13), and high ambient temperature (OR = 0.89, 95% CI 0.79-0.98) were significant protective factors for hypothermia. In contrast, major-plus operations (OR = 2.00, 95% CI 1.32-3.04), duration of anesthesia (1-2 h) (OR = 3.23, 95% CI 2.19-4.78) and >2 h (OR = 3.44, 95% CI 1.90-6.22,), and intravenous un-warmed fluid (OR = 2.45, 95% CI 1.45-4.12) significantly increased the risk of hypothermia. CONCLUSIONS: The incidence of inadvertent intraoperative hypothermia in Beijing is high, and the rate of active warming of patients during operation is low. Concern for the development of intraoperative hypothermia should be especially high in patients undergoing major operations, requiring long periods of anesthesia, and receiving un-warmed intravenous fluids. PMID- 26360774 TI - Macrophage Interaction with Paracoccidioides brasiliensis Yeast Cells Modulates Fungal Metabolism and Generates a Response to Oxidative Stress. AB - Macrophages are key players during Paracoccidioides brasiliensis infection. However, the relative contribution of the fungal response to counteracting macrophage activity remains poorly understood. In this work, we evaluated the P. brasiliensis proteomic response to macrophage internalization. A total of 308 differentially expressed proteins were detected in P. brasiliensis during infection. The positively regulated proteins included those involved in alternative carbon metabolism, such as enzymes involved in gluconeogenesis, beta oxidation of fatty acids and amino acids catabolism. The down-regulated proteins during P. brasiliensis internalization in macrophages included those related to glycolysis and protein synthesis. Proteins involved in the oxidative stress response in P. brasiliensis yeast cells were also up-regulated during macrophage infection, including superoxide dismutases (SOD), thioredoxins (THX) and cytochrome c peroxidase (CCP). Antisense knockdown mutants evaluated the importance of CCP during macrophage infection. The results suggested that CCP is involved in a complex system of protection against oxidative stress and that gene silencing of this component of the antioxidant system diminished the survival of P. brasiliensis in macrophages and in a murine model of infection. PMID- 26360775 TI - Enriched Bone Marrow Derived Disseminated Neuroblastoma Cells Can Be a Reliable Source for Gene Expression Studies-A Validation Study. AB - BACKGROUND: Metastases in the bone marrow (BM) in form of disseminated tumor cells (DTCs) are frequent events at diagnosis and also at relapse in high-risk neuroblastoma patients. The frequently highly diluted occurrence of DTCs requires adequate enrichment strategies to enable their detailed characterization. However, to avoid methodical artifacts we tested whether pre-analytical processing steps-including transport duration, temperature and, importantly, tumor cell enrichment techniques-are confounding factors for gene expression analysis in DTCs. METHODS: LAN-1 neuroblastoma cells were spiked into tumor free BM and/or peripheral blood and: i) kept at room temperature or at 4 degrees C for 24, 48 and 72 hours; ii) frozen down at -80 degrees C and thawed; iii) enriched via magnetic beads. The effect on the gene expression signature of LAN-1 cells was analyzed by qPCR arrays and gene expression microarrays. RESULTS: Neither storage at -80 degrees C in DMSO and subsequent thawing nor enrichment of spiked in neuroblastoma cells changed the expression of the analyzed genes significantly. Whereas storage at 4 degrees C altered the expression of analyzed genes (14.3%) only at the 72h-timepoint in comparison to the 0h-timepoint, storage at room temperature had a much more profound effect on gene expression by affecting 20% at 24h, 26% at 48h and 43% at 72h of the analyzed genes. CONCLUSION: Using neuroblastoma as a model, we show that tumor cell enrichment by magnetic bead separation has virtually no effect on gene expression in DTCs. However, transport time and temperature can influence the expression profile remarkably. Thus, the expression profile of routinely collected BM samples can be analyzed without concern as long as the transport conditions are monitored. PMID- 26360777 TI - Development of a high-throughput real time PCR based on a hot-start alternative for Pfu mediated by quantum dots. AB - Hot start (HS) PCR is an excellent alternative for high-throughput real time PCR due to its ability to prevent nonspecific amplification at low temperature. Development of a cost-effective and simple HS PCR technique to guarantee high throughput PCR specificity and consistency still remains a great challenge. In this study, we systematically investigated the HS characteristics of QDs triggered in real time PCR with EvaGreen and SYBR Green I dyes by the analysis of amplification curves, standard curves and melting curves. Two different kinds of DNA polymerases, Pfu and Taq, were employed. Here we showed that high specificity and efficiency of real time PCR were obtained in a plasmid DNA and an error-prone two-round PCR assay using QD-based HS PCR, even after an hour preincubation at 50 degrees C before real time PCR. Moreover, the results obtained by QD-based HS PCR were comparable to a commercial Taq antibody DNA polymerase. However, no obvious HS effect of QDs was found in real time PCR using Taq DNA polymerase. The findings of this study demonstrated that a cost-effective high-throughput real time PCR based on QD triggered HS PCR could be established with high consistency, sensitivity and accuracy. PMID- 26360776 TI - Cloacal Microbiome Structure in a Long-Distance Migratory Bird Assessed Using Deep 16sRNA Pyrosequencing. AB - Effects of vertebrate-associated microbiota on physiology and health are of significant interest in current biological research. Most previous studies have focused on host-microbiota interactions in captive-bred mammalian models. These interactions and their outcomes are still relatively understudied, however, in wild populations and non-mammalian taxa. Using deep pyrosequencing, we described the cloacal microbiome (CM) composition in free living barn swallows Hirundo rustica, a long-distance migratory passerine bird. Barn swallow CM was dominated by bacteria of the Actinobacteria, Proteobacteria and Firmicutes phyla. Bacteroidetes, which represent an important proportion of the digestive tract microbiome in many vertebrate species, was relatively rare in barn swallow CM (< 5%). CM composition did not differ between males and females. A significant correlation of CM within breeding pair members is consistent with the hypothesis that cloacal contact during within-pair copulation may promote transfer of bacterial assemblages. This effect on CM composition had a relatively low effect size, however, possibly due to the species' high level of sexual promiscuity. PMID- 26360778 TI - Pre-transplant weight loss predicts inferior outcome after allogeneic stem cell transplantation in patients with myelodysplastic syndrome. AB - Allogeneic stem cell transplantation (alloSCT) represents a curative therapeutic option for patients with myelodysplastic syndrome (MDS), but relapse and non relapse mortality (NRM) limit treatment efficacy. Based on our previous observation in acute myeloid leukemia we investigated the impact of pre transplant weight loss on post-transplant outcome in MDS patients. A total of 111 patients diagnosed with MDS according to WHO criteria transplanted between 2000 and 2012 in three different transplant centers were included into the analysis. Data on weight loss were collected from medical records prior to conditioning therapy and 3-6 months earlier. Patient, disease and transplant characteristics did not differ between patients with weight loss (2-5%, n = 17; > 5%, n = 17) and those without (n = 77). In a mixed effect model, weight loss was associated with higher risk MDS (p = 0.046). In multivariable analyses, pre-transplant weight loss exceeding 5% was associated with a higher incidence of relapse (p < 0.001) and NRM (p = 0.007). Pre-transplant weight loss of 2-5% and > 5% were independent predictors of worse disease-free (p = 0.023 and p < 0.001, respectively) and overall survival (p = 0.043 and p < 0.001, respectively). Our retrospective study suggests that MDS patients losing weight prior to alloSCT have an inferior outcome after transplantation. Prospective studies addressing pre-transplant nutritional interventions are highly warranted. PMID- 26360779 TI - Twist1-mediated 4E-BP1 regulation through mTOR in non-small cell lung cancer. AB - Twist1 overexpression corresponds with poor survival in non-small cell lung cancer (NSCLC), but the underlining mechanism is not clear. The objective of the present study was to investigate the tumorigenic role of Twist1 and its related molecular mechanisms in NSCLC. Twist1 was overexpressed in 34.7% of NSCLC patients. The survival rate was significantly lower in patients with high Twist1 expression than low expression (P < 0.05). Twist1 expression levels were higher in H1650 cells, but relatively lower in H1975 cells. H1650 with stable Twist1 knockdown, H1650shTw, demonstrated a significantly slower rate of wound closure; however, H1975 with stable Twist1 overexpression, H1975Over, had an increased motility velocity. A significant decrease in colony number and size was observed in H1650shTw, but a significant increase in colony number was found in H1975Over (P < 0.05). Tumor growth significantly decreased in mice implanted with H1650shTw compared to H1650 (P < 0.05). 4E-BP1 and p53 gene expressions were increased, but p-4E-BP1 and p-mTOR protein expressions were decreased in H1650shTw. However, 4E BP1 gene expression was decreased, while p-4E-BP1 and p-mTOR protein expressions were increased in H1975Over. p-4E-BP1 was overexpressed in 24.0% of NSCLC patients. Survival rate was significantly lower in patients with high p-4E-BP1 expression than low p-4E-BP1 (P < 0.01). A significant correlation was found between Twist1 and p-4E-BP1 (P < 0.01). A total of 13 genes in RT-PCR array showed significant changes in H1650shTw. Altogether, Twist1 is correlated with p 4E-BP1 in predicting the prognostic outcome of NSCLC. Inhibition of Twist1 decreases p-4E-BP1 expression possibly through downregulating p-mTOR and increasing p53 expression in NSCLC. PMID- 26360780 TI - MiRNA-101 inhibits breast cancer growth and metastasis by targeting CX chemokine receptor 7. AB - Whereas miR-101 is involved in the development and progression of breast cancer, the underlying molecular mechanisms remain to be elucidated. Here, we report that miR-101 expression is inversely correlated with the clinical stage, lymph node metastasis and prognosis in breast cancers. Introduction of miR-101 inhibited breast cancer cell proliferation and invasion in vitro and suppressed tumor growth and lung metastasis of in vivo. CX chemokine receptor 7 (CXCR7) is a direct target of miR-101, positively correlating with the histological grade and the incidence of lymph node metastasis in breast cancer patients. The effects of miR-101 were mimicked and counteracted by CXCR7 depletion and overexpression, respectively. STAT3 signaling downstream of CXCR7 is involved in miR-101 regulation of breast cancer cell behaviors. These findings have implications for the potential application of miR-101 in breast cancer treatment. PMID- 26360783 TI - Enhancing the reversibility of Mg/S battery chemistry through Li(+) mediation. AB - Mg metal is a promising anode material for next generation rechargeable battery due to its dendrite-free deposition and high capacity. However, the best cathode for rechargeable Mg battery was based on high molecular weight MgxMo3S4, thus rendering full cell energetically uncompetitive. To increase energy density, high capacity cathode material like sulfur is proposed. However, to date, only limited work has been reported on Mg/S system, all plagued by poor reversibility attributed to the formation of electrochemically inactive MgSx species. Here, we report a new strategy, based on the effect of Li(+) in activating MgSx species, to conjugate a dendrite-free Mg anode with a reversible polysulfide cathode and present a truly reversible Mg/S battery with capacity up to 1000 mAh/gs for more than 30 cycles. Mechanistic insights supported by spectroscopic and microscopic characterization strongly suggest that the reversibility arises from chemical reactivation of MgSx by Li(+). PMID- 26360781 TI - Overexpression of CHD1L is positively associated with metastasis of lung adenocarcinoma and predicts patients poor survival. AB - CHD1L (chromodomain helicase/ATPase DNA binding protein 1-like gene) has been demonstrated as an oncogene in hepatocellular carcinoma (HCC), however, the role of CHD1L in non-small-cell lung cancer (NSCLC) tumorigenesis hasn't been elucidated. In this study, the expression and amplification status of CHD1L were examined by immunohistochemistry and fluorescence in situ hybridization respectively in 248 surgically resected NSCLCs. The associations between CHD1L expression and clinicopathologic features and the prognostic value of CHD1L were analyzed. Overexpression and amplification of CHD1L was found in 42.1% and 17.7% of NSCLCs, respectively. The frequency of CHD1L overexpression (53.2% vs. 28.1%, P = 0.002) and amplification (25.2% vs. 8.2%, P = 0.020) in adenocarcinoma (ADC), was much higher than that in squamous cell carcinoma (SCC). CHD1L overexpression was associated closely with ascending pN status (P < 0.001), advanced clinical stage (P = 0.001) and tumor distant metastasis (P = 0.001) in ADCs, but not in SCCs. For the whole cohort and ADC patients, univariate survival analysis demonstrated a significant association of CHD1L overexpression with shortened survival; and in multivariate analysis, CHD1L overexpression was evaluated as a independent predictor for overall survival and distant metastasis free survival. These results suggested that overexpression of CHD1L is positively associated with tumor metastasis of lung ADC, and might serve as a novel prognostic biomarker and potential therapeutic target for lung ADC patients. PMID- 26360782 TI - Bradykinin inhibits oxidative stress-induced senescence of endothelial progenitor cells through the B2R/AKT/RB and B2R/EGFR/RB signal pathways. AB - Circulating endothelial progenitor cells (EPCs) have multiple protective effects that facilitate repair of damage to tissues and organs. However, while various stressors are known to impair EPC function, the mechanisms of oxidative stress induced EPC senescence remains unknown. We demonstrated that B2 receptor (B2R) expression on circulating CD34(+) cells was significantly reduced in patients with diabetes mellitus (DM) as compared to healthy controls. Furthermore, CD34(+) cell B2R expression in patients with DM was inversely correlated with plasma myeloperoxidase concentrations. Bradykinin (BK) treatment decreased human EPC (hEPC) senescence and intracellular oxygen radical production, resulting in reduced retinoblastoma 1 (RB) RNA expression in H2O2-induced senescent hEPCs and a reversal of the B2R downregulation that is normally observed in senescent cells. Furthermore, BK treatment of H2O2-exposed cells leads to elevated phosphorylation of RB, AKT, and cyclin D1 compared with H2O2-treatment alone. Antagonists of B2R, PI3K, and EGFR signaling pathways and B2R siRNA blocked BK protective effects. In summary, this study demonstrates that BK significantly inhibits oxidative stress-induced hEPC senescence though B2R-mediated activation of PI3K and EGFR signaling pathways. PMID- 26360784 TI - Vocal fundamental and formant frequencies affect perceptions of speaker cooperativeness. AB - In recent years, the perception of social traits in faces and voices has received much attention. Facial and vocal masculinity are linked to perceptions of trustworthiness; however, while feminine faces are generally considered to be trustworthy, vocal trustworthiness is associated with masculinized vocal features. Vocal traits such as pitch and formants have previously been associated with perceived social traits such as trustworthiness and dominance, but the link between these measurements and perceptions of cooperativeness have yet to be examined. In Experiment 1, cooperativeness ratings of male and female voices were examined against four vocal measurements: fundamental frequency (F0), pitch variation (F0-SD), formant dispersion (Df), and formant position (Pf). Feminine pitch traits (F0 and F0-SD) and masculine formant traits (Df and Pf) were associated with higher cooperativeness ratings. In Experiment 2, manipulated voices with feminized F0 were found to be more cooperative than voices with masculinized F0(,) among both male and female speakers, confirming our results from Experiment 1. Feminine pitch qualities may indicate an individual who is friendly and non-threatening, while masculine formant qualities may reflect an individual that is socially dominant or prestigious, and the perception of these associated traits may influence the perceived cooperativeness of the speakers. PMID- 26360785 TI - Age at menarche and endometrial cancer risk: a dose-response meta-analysis of prospective studies. AB - Evidence between age at menarche and endometrial cancer risk have been controversial. Therefore, we conducted a meta-analysis of prospective studies to analyze the aforementioned association. Relevant studies were identified by searching PubMed and EMBASE databases until the end of June 2015. A random effects model was used to estimate summary relative risks (RRs) and 95% confidence intervals (CIs) for associations between menarcheal age and endometrial cancer risk. Our meta-analysis included eight prospective studies involving 4553 subjects with endometrial cancer. The summarized RRs of endometrial cancer for menarcheal age were 0.68 (95%CI = 0.58-0.81, I(2) = 41.9%, P = 0.099, n = 8) when comparing women with oldest category of menarcheal age with women with youngest category of menarcheal age. Notably, there was an 4% reduction in risk for per 2 years delay in menarcheal age (summarized RR = 0.96; 95%CI = 0.94-0.98, I(2) = 45.7%, P = 0.101, n = 6). Additionally, significant inverse associations were consistent within all stratified analyses. There was no evidence of publication bias or significant heterogeneity between subgroups detected by meta-regression analyses. Our findings support the hypothesis that late menarcheal age is inversely associated with endometrial cancer risk. Further larger prospective or pooled studies are warranted to fully adjust for potential confounders and distinguish whether the associations differ by histological subtypes of endometrial cancer. PMID- 26360786 TI - The positive piezoconductive effect in graphene. AB - As the thinnest conductive and elastic material, graphene is expected to play a crucial role in post-Moore era. Besides applications on electronic devices, graphene has shown great potential for nano-electromechanical systems. While interlayer interactions play a key role in modifying the electronic structures of layered materials, no attention has been given to their impact on electromechanical properties. Here we report the positive piezoconductive effect observed in suspended bi- and multi-layer graphene. The effect is highly layer number dependent and shows the most pronounced response for tri-layer graphene. The effect, and its dependence on the layer number, can be understood as resulting from the strain-induced competition between interlayer coupling and intralayer transport, as confirmed by the numerical calculations based on the non equilibrium Green's function method. Our results enrich the understanding of graphene and point to layer number as a powerful tool for tuning the electromechanical properties of graphene for future applications. PMID- 26360787 TI - Bayesian Network Inference Enables Unbiased Phenotypic Anchoring of Transcriptomic Responses to Cigarette Smoke in Humans. AB - Microarray-based transcriptomic analysis has been demonstrated to hold the opportunity to study the effects of human exposure to, e.g., chemical carcinogens at the whole genome level, thus yielding broad-ranging molecular information on possible carcinogenic effects. Since genes do not operate individually but rather through concerted interactions, analyzing and visualizing networks of genes should provide important mechanistic information, especially upon connecting them to functional parameters, such as those derived from measurements of biomarkers for exposure and carcinogenic risk. Conventional methods such as hierarchical clustering and correlation analyses are frequently used to address these complex interactions but are limited as they do not provide directional causal dependence relationships. Therefore, our aim was to apply Bayesian network inference with the purpose of phenotypic anchoring of modified gene expressions. We investigated a use case on transcriptomic responses to cigarette smoking in humans, in association with plasma cotinine levels as biomarkers of exposure and aromatic DNA-adducts in blood cells as biomarkers of carcinogenic risk. Many of the genes that appear in the Bayesian networks surrounding plasma cotinine, and to a lesser extent around aromatic DNA-adducts, hold biologically relevant functions in inducing severe adverse effects of smoking. In conclusion, this study shows that Bayesian network inference enables unbiased phenotypic anchoring of transcriptomics responses. Furthermore, in all inferred Bayesian networks several dependencies are found which point to known but also to new relationships between the expression of specific genes, cigarette smoke exposure, DNA damaging-effects, and smoking-related diseases, in particular associated with apoptosis, DNA repair, and tumor suppression, as well as with autoimmunity. PMID- 26360788 TI - Improving patient-centered communication of the borderline personality disorder diagnosis. AB - BACKGROUND: Borderline personality disorder (BPD) has historically been difficult to diagnose, and laden with stigma, leading to a variety of clinical responses to patients who present with symptoms. AIMS: (1) To understand how clinicians communicate the diagnosis of BPD with patients. (2) To compare these practices with patient communication preferences. (3) To use patient preferences to evaluate clinician practices. METHODS: Semi-structured interviews with mental health care providers and experts (n = 32) were compared with patients (n = 10) and primary patient-written accounts (n = 22). Grounded theory was used to explore causal pathways between clinical practice and patient responses. RESULTS: The majority of clinicians sampled did not actively share the BPD diagnosis with their patients, even when they felt it was the most appropriate diagnosis. The majority of patients wanted to be told that they had the disorder, as well as have their providers discuss the stigma they would face. Patients who later discovered that their diagnosis had been withheld consistently left treatment. CONCLUSIONS: Clinicians believed that by not using the BPD label they were acknowledging or sidestepping the stigma of the condition. However, from the perspective of patients, open communication was essential for maintaining a therapeutic relationship. PMID- 26360789 TI - Measurement of testosterone: how important is a morning blood draw? AB - OBJECTIVE: Since testosterone levels exhibit a circadian variation with peak levels in the morning, evidence-based guidelines recommend measuring morning total testosterone (TT) levels as the initial diagnostic test for androgen deficiency. However, it has been suggested that morning blood draw may not be necessary in older men due to a blunted circadian rhythm. We sought to determine whether it is possible to expand the morning sampling window for measurement of TT. RESEARCH DESIGN AND METHODS: TT levels were measured in a subset of men (mean age of 61 years) participating in the 2013 Prostate Cancer Awareness Week. RESULTS: TT levels measured in blood drawn from 8 to 11 AM (n = 229) differed significantly from those drawn outside this window (n = 442) (411.7 vs 368.3 ng/dl; p = 0.0003). Differences in TT levels were evident across five blood draw time windows (p = < 0.0001) and persisted after adjustment for age and BMI. TT levels in blood drawn from 2 to 5 PM (344.3 ng/dl) and 5 to 8 PM (334.4 ng/dl) differed significantly from that drawn from 8 to 11 AM (p < 0.05), while TT levels from 11 AM to 2 PM (396.5 ng/dl) and 8 PM to 8 AM (373.4 ng/dl) did not (p = 0.90 and 0.73, respectively). CONCLUSION: Based on these findings, it may be possible to expand the blood draw time window for measurement of serum TT. This community-based study was not prospectively design to determine the most appropriate blood draw window for TT measurement. Only a single TT measurement was made without consideration for day-to-day variability, and TT levels were not measured in the same men at different blood draw times. PMID- 26360790 TI - Adipose-derived stromal cells mediate in vivo adipogenesis, angiogenesis and inflammation in decellularized adipose tissue bioscaffolds. AB - Decellularized adipose tissue (DAT) has shown promise as an adipogenic bioscaffold for soft tissue augmentation and reconstruction. The objective of the current study was to investigate the effects of allogeneic adipose-derived stem/stromal cells (ASCs) on in vivo fat regeneration in DAT bioscaffolds using an immunocompetent rat model. ASC seeding significantly enhanced angiogenesis and adipogenesis, with cell tracking studies indicating that the newly-forming tissues were host-derived. Incorporating ASCs also mediated the inflammatory response and promoted a more constructive macrophage phenotype. A fraction of the CD163(+) macrophages in the implants expressed adipogenic markers, with higher levels of this "adipocyte-like" phenotype in proximity to the developing adipose tissues. Our results indicate that the combination of ASCs and adipose extracellular matrix (ECM) provides an inductive microenvironment for adipose regeneration mediated by infiltrating host cell populations. The DAT scaffolds are a useful tissue-specific model system for investigating the mechanisms of in vivo adipogenesis that may help to develop a better understanding of this complex process in the context of both regeneration and disease. Overall, combining adipose-derived matrices with ASCs is a highly promising approach for the in situ regeneration of host-derived adipose tissue. PMID- 26360791 TI - Treatment options for mantle cell lymphoma. AB - INTRODUCTION: In this article, we provide an accurate overview of both standard treatment option and novel promising therapeutics. Major impact is on novel agents now being tested in randomized clinical trials. While the initial data are promising, they may rapidly expand treatment options, change existing paradigms and further improve outcomes for mantle cell lymphoma (MCL) patients. AREAS COVERED: MCL is a disease with indolent histology, but aggressive clinical course. However, for now, MCL remains incurable and the search for the most effective and tumor-specific treatment still represents a great challenge for oncohematologists. However, the implementation of chemotherapy together with the anti-CD20 antibody rituximab, as well as the growing use of autologous stem cell transplantation in first remission, have improved effects of treatment in MCL, including even some improvement in overall survival. Recently, treatment modalities for MCL have been expanded by strategies based on several biologically targeted agents, including m-TOR kinase or proteasome inhibitors and immunomodulatory agents, such as lenalidomide. B-cell receptor pathway inhibitors, such as ibrutinib and idelalisib, and histone deacetylase or cyclin dependent kinase inhibitors have also shown promising activity in resistant or relapsed disease. EXPERT OPINION: Although enormous progress was made in the treatment of MCL over the last year, the disease remains incurable. One chance for the significant life prolongation is intensive treatment with consolidative auto SCT. However, real progress may be afforded by developing the novel agents described in this article. In this way, MCL may soon become another potentially curable oncological malignancy. PMID- 26360792 TI - Discussing mental illness in Chinese social media: the impact of influential sources on stigmatization and support among their followers. AB - A content analysis was conducted to examine depression-related discourses by public opinion leaders and mainstream media in the Chinese social media platform Sina Weibo, as well as the impact of these discourses on their followers. The study revealed that stereotypical presentations of people with depression by influential sources often promoted stigmatization of or reduced support for depressed individuals among their followers. Environmental and genetic attributions for the disease in the original posts reduced stigmatization in the response posts. Information about recovery and treatment proved to be a double edged sword, reducing stigmatization and support among followers at the same time. The use of a crime context to discuss depression in the original posts often promoted stigmatization, while discussing it in a health context increased support in the response posts. PMID- 26360793 TI - Editorial Comment for Sfoungaristos et al. PMID- 26360797 TI - Speech pathology and occupational therapy students participating in placements where their supervisor works in a dual role. AB - OBJECTIVE: To investigate the facilitating factors and barriers to students participating in placements where their supervisor works in a dual role. DESIGN: A combination of semi structured interviews and focus groups were used. Data was analysed using thematic analysis. SETTING: Regional brain injury rehabilitation programs and university programs. PARTICIPANTS: Eleven Speech Pathologists or Occupational Therapists who worked in regional brain injury rehabilitation programs as both a case manager and within their discipline. Five Speech Pathology or Occupational Therapy university academics who were employed in a role central to facilitating student clinical placements. RESULTS: 6 themes emerged. These included the supervisor's experience of a non-traditional model, communication, perceptions of a clinical placement, supervision, student cohort and assessment criteria. CONCLUSIONS: It appears that students are able to participate in placements where their supervisor works within a specific discipline, as well as a case manager. There are particular factors that are likely to make this experience successful. It is important for all stakeholders to communicate about the placement and their expectations, which may assist with managing perceptions of what an appropriate placement is. Utilising different supervisory models is also necessary. There are factors that do not appear to have a significant effect on the success of such a placement. There is no consensus about the particular level of experience that a student should have to manage this type of placement. The assessment criteria that supervisors are required to complete does not appear to be a barrier to students participating. While there are challenges, benefits for all stakeholders are identified. PMID- 26360794 TI - Molecular Characterization of Staphylococcus aureus Isolates Transmitted between Patients with Buruli Ulcer. AB - BACKGROUND: Buruli ulcer (BU) is a skin infection caused by Mycobacterium ulcerans. The wounds of most BU patients are colonized with different microorganisms, including Staphylococcus aureus. METHODOLOGY: This study investigated possible patient-to-patient transmission events of S. aureus during wound care in a health care center. S. aureus isolates from different BU patients with overlapping visits to the clinic were whole-genome sequenced and analyzed by a gene-by-gene approach using SeqSphere(+) software. In addition, sequence data were screened for the presence of genes that conferred antibiotic resistance. PRINCIPAL FINDINGS: SeqSphere(+) analysis of whole-genome sequence data confirmed transmission of methicillin resistant S. aureus (MRSA) and methicillin susceptible S. aureus among patients that took place during wound care. Interestingly, our sequence data show that the investigated MRSA isolates carry a novel allele of the fexB gene conferring chloramphenicol resistance, which had thus far not been observed in S. aureus. PMID- 26360798 TI - Utility of preoperative computed tomography and magnetic resonance imaging in adult and pediatric cochlear implant candidates. AB - OBJECTIVES/HYPOTHESIS: Determine the utility of preoperative imaging in adult and pediatric cochlear implant candidates. STUDY DESIGN: Retrospective chart review. METHODS: Medical records of 101 consecutive adult and 20 consecutive pediatric patients who underwent 137 cochlear implantation (CI) procedures at a single institution were reviewed. RESULTS: Computed tomography (CT) was obtained preoperatively in 110 (90.9%) patients, preoperative magnetic resonance imaging (MRI) was obtained in 102 (84.3%) patients, and both were obtained in 94 (77.7%) patients. MRI revealed one acoustic neuroma and two meningiomas, which affected surgical planning for three (2.2%) procedures. MRI identified enlarged vestibular aqueduct (EVA) in 2.0% of adult patients. CT demonstrated middle ear disease in four (3.3%) patients. CT was useful in indicating round window and cochlear patency in three (2.2%) patients with cochlear otosclerosis. Twenty pediatric patients underwent 27 CI procedures. Preoperative CT in the pediatric cohort demonstrated five (25%) dysplastic cochleae, three (15%) dysplastic vestibules and/or semicircular canals, and three (15%) EVAs. In one patient, CT demonstrated a duplicated right internal auditory canal (IAC) and hypoplastic left IAC; MRI confirmed hypoplastic cochlear nerves. CONCLUSIONS: Preoperative MRI can demonstrate retrocochlear pathology, cochlear patency, and EVA in adults being evaluated for cochlear implantation. CT may provide additional information in patients with chronic otitis media or otosclerosis. However, in postlingually deafened adults without conductive or asymmetrical hearing loss, imaging is unlikely to affect surgical decision making. Both CT and MRI can identify anomalies in pediatric patients. MRI does not offer substantial benefit over CT for routine evaluation of pediatric inner ear and temporal bone anatomy. LEVEL OF EVIDENCE: 4 Laryngoscope, 126:1440-1445, 2016. PMID- 26360799 TI - 'The world has changed': pharmaceutical citizenship and the reimagining of serodiscordant sexuality among couples with mixed HIV status in Australia. AB - In this article, I revisit the question of whether HIV can ever be reimagined and re-embodied as a potentially non-infectious condition, drawing on a current qualitative study of couples with mixed HIV status (serodiscordance) in Australia. Recent clinical trials have consolidated a shift in scientific understandings of HIV infectiousness by showing that antiretroviral treatment effectively prevents the sexual transmission of HIV. Contrary to common critiques, I explore how the increasing biomedicalisation of public health and the allied discourse of 'normalisation' can in fact de-marginalise stigmatised relationships and sexualities. Invoking Ecks's concept of 'pharmaceutical citizenship', I consider whether the emerging global strategy of HIV 'treatment as-prevention' (TasP) can open up new trajectories that release serodiscordant sexuality from its historical moorings in discourses of risk and stigma, and whether these processes might re-inscribe serodiscordant sexuality as 'normal' and safe, potentially shifting the emphasis in HIV prevention discourses away from sexual practice toward treatment uptake and adherence. PMID- 26360800 TI - Increased risk of male cancer and identification of a potential prostate cancer cluster region in BRCA2. AB - BACKGROUND: The risk of cancer in men from BRCA1 and BRCA2 families is relevant to define to motivate genetic testing and optimize recommendations for surveillance. MATERIAL AND METHODS: We assessed the risk of cancer in male mutation carriers and their first-degree relatives in 290 BRCA1 and BRCA2 families with comparison to matched controls with the aim to motivate genetic testing and optimize recommendations for surveillance. RESULTS: Mutation carriers in BRCA1 families were not at increased risk of cancer, whereas mutation carriers in BRCA2 families were at increased risk of male breast cancer and prostate cancer with cumulative risks of 12.5% and 18.8%, respectively. Breast cancer developed at a mean age of 59 years, typically as ER/PR positive ductal carcinomas. Prostate cancer developed at a mean age of 68 years, with Gleason scores >= 8 in 40% of the tumors. The hazard ratio for BRCA2-associated prostate cancer was 3.7 (p < 0.001) in mutation carriers and 3.1 (p = 0.001) in first degree relatives. Of the 37 prostate cancers, 19 were linked to four BRCA2 mutations within a region defined by c.6373-c.6492. Individuals with mutations herein had a HR of 3.7 for prostate cancer compared to individuals with mutations outside of this region. CONCLUSIONS: Male mutation carriers and first-degree relatives in BRCA2 families are at an increased risk of breast cancer and prostate cancer with a potential prostate cancer cluster region within exon 11 of BRCA2. PMID- 26360801 TI - Expression of beta-glucosidase increases trichome density and artemisinin content in transgenic Artemisia annua plants. AB - Artemisinin is highly effective against multidrug-resistant strains of Plasmodium falciparum, the aetiological agent of the most severe form of malaria. However, a low level of accumulation of artemisinin in Artemisia annua is a major limitation for its production and delivery to malaria endemic areas of the world. While several strategies to enhance artemisinin have been extensively explored, enhancing storage capacity in trichome has not yet been considered. Therefore, trichome density was increased with the expression of beta-glucosidase (bgl1) gene in A. annua through Agrobacterium-mediated transformation. Transgene (bgl1) integration and transcript were confirmed by molecular analysis. Trichome density increased up to 20% in leaves and 66% in flowers of BGL1 transgenic plants than Artemisia control plants. High-performance liquid chromatography, time of flight mass spectrometer data showed that artemisinin content increased up to 1.4% in leaf and 2.56% in flowers (per g DW), similar to the highest yields achieved so far through metabolic engineering. Artemisinin was enhanced up to five-fold in BGL1 transgenic flowers. This study opens the possibility of increasing artemisinin content by manipulating trichomes' density, which is a major reservoir of artemisinin. Combining biosynthetic pathway engineering with enhancing trichome density may further increase artemisinin yield in A. annua. Because oral feeding of Artemisia plant cells reduced parasitemia more efficiently than the purified drug, reduced drug resistance and cost of prohibitively expensive purification process, enhanced expression should play a key role in making this valuable drug affordable to treat malaria in a large global population that disproportionally impacts low-socioeconomic areas and underprivileged children. PMID- 26360802 TI - The synthesis and characterization of the 'research chemical' N-(1-amino-3-methyl 1-oxobutan-2-yl)-1-(cyclohexylmethyl)-3-(4-fluorophenyl)-1H-pyrazole-5 carboxamide (3,5-AB-CHMFUPPYCA) and differentiation from its 5,3-regioisomer. AB - This study presents the identification of N-(1-amino-3-methyl-1-oxobutan-2-yl)-1 (cyclohexylmethyl)-3-(4-fluorophenyl)-1H-pyrazole-5-carboxamide that was termed 3,5-AB-CHMFUPPYCA. This compound was obtained from a UK-based Internet vendor, who erroneously advertised this 'research chemical' as AZ-037 and which would have been associated with (S)-N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-(5 fluoropentyl)-5-(4-fluorophenyl)-1H-pyrazole-3-carboxamide. The presence of the pyrazole core indicates a bioisosteric replacement of an indazole ring that is frequently associated with synthetic cannabinoids of the PINACA, FUBINACA, and CHMINACA series. The pyrazole ring system present in 3,5-AB-CHMFUPPYCA gives rise to the regioisomer N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-(cyclohexylmethyl)-5-(4 fluorophenyl)-1H-pyrazole-3-carboxamide (named 5,3-AB-CHMFUPPYCA) and both isomers were synthesized using two specific routes which supported the correct identification of the 'research chemical' as 3,5-AB-CHMFUPPYCA. Both isomers could be conveniently differentiated. Interestingly, a route specific chlorine containing by-product also was observed during the synthesis of 3,5-AB-CHMFUPPYCA and identified as N-(1-amino-3-methyl-1-oxobutan-2-yl)-4-chloro-1 (cyclohexylmethyl)-3-(4-fluorophenyl)-1H-pyrazole-5-carboxamide. An extensive analytical characterization included chromatographic, spectroscopic, mass spectrometric platforms as well as crystal structure analysis. The syntheses and analytical characterizations of both AB-CHMFUPPYCA isomers are reported for the first time and serves as a reminder that the possibility of mislabeling of 'research chemicals' cannot be excluded. The pharmacological activities of both AB-CHMFUPPYCA isomers remain to be explored. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26360803 TI - Somatic BRAF c.1799T>A p.V600E Mosaicism syndrome characterized by a linear syringocystadenoma papilliferum, anaplastic astrocytoma, and ocular abnormalities. AB - Genetic mosaicism for somatic mutations of oncogenes is common in genodermatoses, which can be complicated with extra-cutaneous abnormalities. Here we describe an infant with a congenital anaplastic astrocytoma, a linear syringocystadenoma papilliferum, and ocular abnormalities. The BRAF c.1799T>A p.V600E mutation was detected in both the brain and skin tumor cells but not in the blood or normal skin cells, suggesting somatic mosaicsism for the mutation. Clinically, the brain tumor gradually became life threatening without any response to conventional chemotherapies including carboplatin, etoposide, and temozolomide. Vemurafenib, a BRAF p.V600E inhibitor, was administered daily after the detection of the BRAF mutation. This single-agent therapy was dramatically effective against the anaplastic astrocytoma; the tumor regressed, the cerebrospinal fluid cell count and protein levels decreased to normal levels, and hydrocephalus resolved. Moreover, other lesions including a corneal cyst also responded to vemurafenib. The brain tumor continued shrinking after 6 months of treatment. We present a genodermatosis syndrome associated with BRAF c.1799T>A p.V600E mosaicism. This syndrome may represent a new entity in the mosaic RASopathies, partly overlapping with Schimmelpenning-Feuerstein-Mims syndrome, which is driven by mosaicism of HRAS and/or KRAS activating mutations. Screening for BRAF c.1799T>A p.V600E is especially useful for those with malignant tumors, because it is one of the most druggable targets. PMID- 26360804 TI - Low-Temperature CO Oxidation over a Ternary Oxide Catalyst with High Resistance to Hydrocarbon Inhibition. AB - Platinum group metal (PGM) catalysts are the current standard for control of pollutants in automotive exhaust streams. Aside from their high cost, PGM catalysts struggle with CO oxidation at low temperatures (<200 degrees C) due to inhibition by hydrocarbons in exhaust streams. Here we present a ternary mixed oxide catalyst composed of copper oxide, cobalt oxide, and ceria (dubbed CCC) that outperforms synthesized and commercial PGM catalysts for CO oxidation in simulated exhaust streams while showing no signs of inhibition by propene. Diffuse reflectance IR (DRIFTS) and light-off data both indicate low interaction between propene and the CO oxidation active site on this catalyst, and a separation of adsorption sites is proposed as the cause of this inhibition resistance. This catalyst shows great potential as a low-cost component for low temperature exhaust streams that are expected to be a characteristic of future automotive systems. PMID- 26360805 TI - Bivariate correlation coefficients in family-type clustered studies. AB - We propose a unified approach based on a bivariate linear mixed effects model to estimate three types of bivariate correlation coefficients (BCCs), as well as the associated variances between two quantitative variables in cross-sectional data from a family-type clustered design. These BCCs are defined at different levels of experimental units including clusters (e.g., families) and subjects within clusters and assess different aspects on the relationships between two variables. We study likelihood-based inferences for these BCCs, and provide easy implementation using standard software SAS. Unlike several existing BCC estimators in the literature on clustered data, our approach can seamlessly handle two major analytic challenges arising from a family-type clustered design: (1) many families may consist of only one single subject; (2) one of the paired measurements may be missing for some subjects. Hence, our approach maximizes the use of data from all subjects (even those missing one of the two variables to be correlated) from all families, regardless of family size. We also conduct extensive simulations to show that our estimators are superior to existing estimators in handling missing data or/and imbalanced family sizes and the proposed Wald test maintains good size and power for hypothesis testing. Finally, we analyze a real-world Alzheimer's disease dataset from a family clustered study to investigate the BCCs across different modalities of disease markers including cognitive tests, cerebrospinal fluid biomarkers, and neuroimaging biomarkers. PMID- 26360806 TI - Evaluation of anticoagulant activity of two algal polysaccharides. AB - Marine algae are important sources of phycocolloids like agar, carrageenans and alginates used in industrial applications. Algal polysaccharides have emerged as an important class of bioactive products showing interesting properties. The aim of our study was to evaluate the potential uses as anticoagulant drugs of algal sulphate polysaccharides extracted from Ulva fasciata (Chlorophyta) and Agardhiella subulata (Rhodophyta) collected in Ganzirri Lake (Cape Peloro Lagoon, north-eastern Sicily, Italy). Toxicity of algal extracts through trypan blue test and anticoagulant action measured by activated partial thromboplastin time (APTT), prothrombin time (PT) test has been evaluated. Algal extracts showed to prolong the PT and APTT during the coagulation cascade and to avoid the blood coagulation of samples. Furthermore, the algal extracts lack toxic effects towards cellular metabolism and their productions are relatively at low cost. This permits to consider the algae as the biological source of the future. PMID- 26360807 TI - Biotinylated Cyclophane: Synthesis, Cyclophane-Avidin Conjugates, and Their Enhanced Guest-Binding Affinity. AB - Cationic and anionic cyclophanes bearing a biotin moiety were synthesized as a water-soluble host (1a and 1b, respectively). Both hosts 1a and 1b were found to strongly bind avidin with binding constants of 1.3 * 10(8) M(-1), as confirmed by surface plasmon resonance measurements. The present conjugate of 1a with avidin (1a-avidin) showed an enhanced guest binding affinity toward fluorescence guests such as TNS and 2,6-ANS. The K values of 1a-avidin conjugate with TNS and 2,6-ANS were ~19-fold larger than those of monocyclic cyclophane 1a with the identical guests. Favorable hydrophobic and electrostatic interactions between 1a-avidin and TNS were suggested by computer-aided molecular modeling calculations. Moreover, addition of excess biotin to the complexes of 1a-avidin with the guests resulted in dissociation of 1a-avidin to avidin and 1a having less guest-binding affinity. Conversely, such enhancements in the guest-binding affinity were not obviously observed for the conjugate of anionic 1b with avidin (1b-avidin) due to electrostatic repulsion between anionic 1b and anionic guests. PMID- 26360808 TI - Response to Moderate Sedation Article by Kennedy et al. PMID- 26360809 TI - Synthesis of Analogues of BCTC Incorporating a Pyrrolidinyl Linker and Biological Evaluation as Transient Receptor Potential Vanilloid 1 Antagonists. AB - A series of novel pyrrolidinyl linker TRPV1 antagonists were prepared in an effort to lower the hyperthermic side-effects of first-generation antagonist BCTC. These compounds were investigated for antagonism of hTRPV1 activation by capsaicin and acid in vitro. Preliminary results suggested the compounds 10a, 10b, 10c and 10j had favorable TRPV1 antagonism activity. In further studies in vivo, 10b, comparable to BCTC, showed potent analgesic activity in capsaicin induced and heat-induced pain models. In addition, 10b indicated a reduced risk of body temperature elevation. All of these demonstrated that 10b can be considered as a safe candidate for the further development of analgesic drugs. PMID- 26360810 TI - Body image and quality of life of breast cancer patients: influence of timing and stage of breast reconstruction. AB - OBJECTIVE: The process of cancer-related breast reconstruction is typically multi staged and can take months to years to complete, yet few studies have examined patient psychosocial well-being during the reconstruction process. We investigated the effects of reconstruction timing and reconstruction stage on body image and quality of life at specific time points during the breast reconstruction process. METHODS: In this cross-sectional study, 216 patients were grouped into four reconstructive stages: pre-reconstruction, completed stage 1, completed stage 2, and final stages. Multiple regression analyses examined the roles of reconstruction timing (immediate vs delayed reconstruction) and reconstruction stage as well as their interaction in predicting body image and quality of life, controlling for patient age, BMI, type of reconstruction, chemotherapy, radiation therapy, and major complication(s). RESULTS: A difference in pattern of body image was observed across the reconstructive stages, with those receiving delayed reconstruction showing significant decrease in body image dissatisfaction compared with those with immediate reconstruction. At pre reconstruction, patients awaiting delayed reconstruction reported significantly lower social well-being compared with those awaiting immediate reconstruction. Reconstruction stage predicted emotional well-being, with higher emotional well being observed in those who had commenced reconstruction. CONCLUSIONS: Timing and stage of reconstruction are important to consider when examining psychosocial outcomes of breast cancer patients undergoing reconstruction. Those waiting to initiate delayed reconstruction appear at particular risk for body image, emotional, and social distress. Our findings have implications for delivery of psychosocial treatment to maximize body image and quality of life of patients undergoing cancer-related breast reconstruction.Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26360811 TI - Design Guidelines for High-Performance Particle-Based Photoanodes for Water Splitting: Lanthanum Titanium Oxynitride as a Model. AB - Semiconductor powders are perfectly suited for the scalable fabrication of particle-based photoelectrodes, which can be used to split water using the sun as a renewable energy source. This systematic study is focused on variation of the electrode design using LaTiO2 N as a model system. We present the influence of particle morphology on charge separation and transport properties combined with post-treatment procedures, such as necking and size-dependent co-catalyst loading. Five rules are proposed to guide the design of high-performance particle based photoanodes by adding or varying several process steps. We also specify how much efficiency improvement can be achieved using each of the steps. For example, implementation of a connectivity network and surface area enhancement leads to thirty times improvement in efficiency and co-catalyst loading achieves an improvement in efficiency by a factor of seven. Some of these guidelines can be adapted to non-particle-based photoelectrodes. PMID- 26360812 TI - Could familial Mediterranean fever gene mutations be related to PFAPA syndrome? AB - BACKGROUND: The cause and pathophysiology of PFAPA syndrome is unknown. The aim of this study was to determine all MEFV gene variants relevant to familial Mediterranean fever in children with PFAPA syndrome. METHODS: All MEFV gene variants were analyzed in patients with PFAPA syndrome. All patients were evaluated using the Gaslini scoring system. Serum immunoglobulin levels were also determined upon admission. RESULTS: We evaluated 64 patients with PFAPA syndrome. The median age at diagnosis was 37.5 (min-max: 6-96) months, and the percentage of male patients was 55.0%. The Gaslini diagnostic score for periodic fever was high in 81.0% of the patients. An MEFV gene mutation was found in 42 (66.0%) children. Mostly, heterozygous or compound heterozygous variants of the MEFV gene were found. Two patients were homozygous for R202Q. MEFV gene mutations were not detected in 22 (34.0%) patients. No significant differences in clinical or laboratory findings were observed between the two groups (p > 0.05), and there were no significant differences in period and duration of the fever episodes (p > 0.05). The fever of all 47 patients (100.0%) who received prednisolone during the episodes decreased within hours and did not recur. Eighteen of the patients using prednisolone underwent prophylaxis with colchicine, and the fever episodes of 9/18 (50.0%) patients using colchicine decreased within months. CONCLUSIONS: Most patients presenting with PFAPA syndrome have heterozygous MEFV gene mutations. Whether carrying a heterozygous MEFV gene is the primary cause of this syndrome requires further investigation. PMID- 26360813 TI - Methyl 3-Hydroxymyristate, a Diffusible Signal Mediating phc Quorum Sensing in Ralstonia solanacearum. AB - Ralstonia solanacearum, a plant pathogenic bacterium causing "bacterial wilt" on crops, uses a quorum sensing (QS) system consisting of phc regulatory elements to control its virulence. Methyl 3-hydroxypalmitate (3-OH PAME) was previously identified as the QS signal in strain AW1. However, 3-OH PAME has not been reportedly detected from any other strains, and this suggests that they produce another unknown QS signal. Here we identify (R)-methyl 3-hydroxymyristate [(R)-3 OH MAME] as a new QS signal that regulates the production of virulence factors and secondary metabolites. (R)-3-OH MAME was synthesized by the methyltransferase PhcB and sensed by the histidine kinase PhcS. The phylogenetic trees of these proteins from R. solanacearum strains were divided into two groups, according to their QS signal types--(R)-3-OH MAME or (R)-3-OH PAME. These results demonstrate that (R)-3-OH MAME is another crucial QS signal and highlight the unique evolution of QS systems in R. solanacearum. PMID- 26360814 TI - Validation of the Hexoskin wearable vest during lying, sitting, standing, and walking activities. AB - We tested the validity of the Hexoskin wearable vest to monitor heart rate (HR), breathing rate (BR), tidal volume (VT), minute ventilation, and hip motion intensity (HMI) in comparison with laboratory standard devices during lying, sitting, standing, and walking. Twenty healthy young volunteers participated in this study. First, participants walked 6 min on a treadmill at speeds of 1, 3, and 4.5 km/h followed by increasing treadmill grades until 80% of their predicted maximal heart rate. Second, lying, sitting, and standing tasks were performed (5 min each) followed by 6 min of treadmill walking at 80% of their ventilatory threshold. Analysis of each individual's mean values under each resting or exercise condition by the 2 measurement systems revealed low coefficient of variation and high intraclass correlation values for HR, BR, and HMI. The Bland Altman results from HR, BR, and HMI indicated no deviation of the mean value from zero and relatively small variability about the mean. VT and minute ventilation were provided in arbitrary units by the Hexoskin device; however, relative magnitude of change from Hexoskin closely tracked the laboratory standard method. Hexoskin presented low variability, good agreement, and consistency. The Hexoskin wearable vest was a valid and consistent tool to monitor activities typical of daily living such as different body positions (lying, sitting, and standing) and various walking speeds. PMID- 26360815 TI - Interrater reliability of mechanical tests for functional classification of transtibial prosthesis components distal to the socket. AB - Substantial evidence suggests that the design and associated mechanical function of lower-limb prostheses affects user health and mobility, supporting common standards of clinical practice for appropriate matching of prosthesis design and user needs. This matching process is dependent on accurate and reliable methods for the functional classification of prosthetic components. The American Orthotic & Prosthetic Association developed a set of tests for L-code characterization of prosthesis mechanical properties to facilitate functional classification of passive below-knee prosthetic components. The mechanical tests require use of test-specific fixtures to be installed in a materials testing machine by a test administrator. Therefore, the purpose of this study was to assess the interrater reliability of test outcomes between two administrators using the same testing facility. Ten prosthetic components (8 feet and 2 pylons) that spanned the range of commercial designs were subjected to all appropriate tests. Tests with scalar outcomes demonstrated high interrater reliability (intraclass correlation coefficient(2,1) >/= 0.935), and there was no discrepancy in observation-based outcomes between administrators, suggesting that between-administrator variability may not present a significant source of error. These results support the integration of these mechanical tests for prosthesis classification, which will help enhance objectivity and optimization of the prosthesis-patient matching process for maximizing rehabilitation outcomes. PMID- 26360816 TI - Proteomic and phosphoproteomic analyses reveal extensive phosphorylation of regulatory proteins in developing rice anthers. AB - Anther development, particularly around the time of meiosis, is extremely crucial for plant sexual reproduction. Meanwhile, cell-to-cell communication between somatic (especial tapetum) cells and meiocytes are important for both somatic anther development and meiosis. To investigate possible molecular mechanisms modulating protein activities during anther development, we applied high resolution mass spectrometry-based proteomic and phosphoproteomic analyses for developing rice (Oryza sativa) anthers around the time of meiosis (RAM). In total, we identified 4984 proteins and 3203 phosphoproteins with 8973 unique phosphorylation sites (p-sites). Among those detected here, 1544 phosphoproteins are currently absent in the Plant Protein Phosphorylation DataBase (P3 DB), substantially enriching plant phosphorylation information. Mapman enrichment analysis showed that 'DNA repair','transcription regulation' and 'signaling' related proteins were overrepresented in the phosphorylated proteins. Ten genetically identified rice meiotic proteins were detected to be phosphorylated at a total of 25 p-sites; moreover more than 400 meiotically expressed proteins were revealed to be phosphorylated and their phosphorylation sites were precisely assigned. 163 putative secretory proteins, possibly functioning in cell-to-cell communication, are also phosphorylated. Furthermore, we showed that DNA synthesis, RNA splicing and RNA-directed DNA methylation pathways are extensively affected by phosphorylation. In addition, our data support 46 kinase-substrate pairs predicted by the rice Kinase-Protein Interaction Map, with SnRK1 substrates highly enriched. Taken together, our data revealed extensive protein phosphorylation during anther development, suggesting an important post translational modification affecting protein activity. PMID- 26360817 TI - One-Step Synthesis of 2-Chloropyrimidin-4-ol Derivatives: An Unusual Reactivity of Thiophosgene. AB - A novel, high-yielding, one-step synthesis of 2-chloroquinazolin-4-ols and analogous bicycles from 2-aminoamides using thiophosgene is described. The scope of the reaction includes aminothioamides, amino acids, and fused heterocycle derivatives, furnishing quinazolines, oxazinones, and substituted fused pyrimidine bicycles, respectively. On the basis of observed results with substituted analogues, a mechanism for this transformation is thought to occur via an isothiocyanate intermediate followed by an unexpected chemoselective reaction of thiophosgene on the thiol intermediate. PMID- 26360818 TI - Who's at Risk When the Power Goes Out? The At-home Electricity-Dependent Population in the United States, 2012. AB - OBJECTIVES: Natural and man-made disasters can result in power outages that can affect certain vulnerable populations dependent on electrically powered durable medical equipment. This study estimated the size and prevalence of that electricity-dependent population residing at home in the United States. METHODS: We used the Truven Health MarketScan 2012 database to estimate the number of employer-sponsored privately insured enrollees by geography, age group, and sex who resided at home and were dependent upon electrically powered durable medical equipment to sustain life. We estimated nationally representative prevalence and used US Census population estimates to extrapolate the national population and produce maps visualizing prevalence and distribution of electricity-dependent populations residing at home. RESULTS: As of 2012, among the 175 million persons covered by employer-sponsored private insurance, the estimated number of electricity-dependent persons residing at home was 366 619 (95% confidence interval: 365 700-367 537), with a national prevalence of 218.2 per 100 000 covered lives (95% confidence interval: 217.7-218.8). Prevalence varied significantly by age group (chi = 264 289 95, P < .0001) and region (chi = 12 286 30, P < .0001), with highest prevalence in those 65 years of age or older and in the South and the West. Across all insurance types in the United States, approximately 685 000 electricity-dependent persons resided at home. CONCLUSIONS: These results may assist public health jurisdictions addressing unique needs and necessary resources for this particularly vulnerable population. Results can verify and enhance the development of functional needs registries, which are needed to help first responders target efforts to those most vulnerable during disasters affecting the power supply. PMID- 26360819 TI - Graphene-Based Bioinspired Compound Eyes for Programmable Focusing and Remote Actuation. AB - Inspired by creatures' eyes, bioinspired compound eyes (BCEs) endowed with larger fields of view and vari-focal capability are extremely appealing in micro-optical devices. However, the present actuation strategies of BCEs commonly demand complicated fields, e.g., electro-wetting actuation, dielectrophoretic drive and pressure gradient, which greatly limits their practical applications. In this work, the photothermal conversion of graphene nanosheets (GNSs) is first utilized to fabricate lenslets toward BCEs. Under the actuation of near-infrared (nIR) pulsed laser, GNSs absorb photo energy and convert it to thermal energy, which increases the temperature of lenslets and then leads to the adjustment of lenslet curvature. At a result, BCEs manifest a reversible 4-fold zoom and a wide FOV up to 160 degrees . In addition, BCEs also perform the programmable focusing by selectively confining nIR laser to a vari-focal region. In contrast with traditional BCEs, graphene-based BCEs are versatile with wide FOV and vari-focal ability by nIR actuation. Herein, these excellent properties make graphene-based BCEs promising for remote-driven microfluidic devices. PMID- 26360821 TI - Rehabilitation Engineering and Assistive Technology Society of North America's Position on the Application of Tilt, Recline, and Elevating Legrests for Wheelchairs Literature Update. PMID- 26360820 TI - Endothelial Cells Expressing Endothelial and Mesenchymal Cell Gene Products in Lung Tissue From Patients With Systemic Sclerosis-Associated Interstitial Lung Disease. AB - OBJECTIVE: To examine whether lung endothelial cells (ECs) from patients with systemic sclerosis (SSc)-associated interstitial lung disease (ILD) express mesenchymal cell-specific proteins and gene transcripts, indicative of the occurrence of endothelial-to-mesenchymal phenotypic transition (EndoMT). METHODS: Lung tissue from 6 patients with SSc-associated pulmonary fibrosis was examined by histopathology and immunohistochemistry. Confocal laser microscopy was utilized to assess the simultaneous expression of EC and myofibroblast molecular markers. CD31+CD102+ ECs were isolated from the lung tissue of 2 patients with SSc-associated ILD and 2 normal control subjects, and the expression of EC and mesenchymal cell markers and other relevant genes was analyzed by quantitative polymerase chain reaction, immunofluorescence microscopy, and Western blotting. RESULTS: Immunohistochemical staining revealed cells expressing the EC-specific marker CD31 in the subendothelial, perivascular, and parenchymal regions of the lungs from all SSc patients. Confocal microscopy identified cells displaying simultaneous expression of von Willebrand factor and alpha-smooth muscle actin in small and medium-sized arterioles in the SSc lung tissue but not in normal control lungs. CD31+CD102+ ECs isolated from SSc lungs expressed high levels of mesenchymal cell-specific genes (type I collagen, type III collagen, and fibronectin), EC-specific genes (type IV collagen and VE-cadherin), profibrotic genes (transforming growth factor beta1 and connective tissue growth factor), and genes encoding EndoMT-related transcription factors (TWIST1 and SNAI2). CONCLUSION: Cells coexpressing EC- and mesenchymal cell-specific molecules are present in the lungs of patients with SSc-associated ILD. CD31+CD102+ ECs isolated from SSc lungs simultaneously expressed mesenchymal cell- and EC specific transcripts and proteins. Collectively, these observations demonstrate the occurrence of EndoMT in the lungs of patients with SSc-associated ILD. PMID- 26360822 TI - Neuroendocrine Carcinoma of the Kidney and Bladder with Loss of Heterozygosity and Changes in Chromosome 3 Copy Number. AB - BACKGROUND: Neuroendocrine carcinomas (NECs) of the urological organs are observed occasionally, although simultaneous development in the kidney and blabber has not been reported. CASE REPORT: We report a case of a metastatic NEC of the kidney and bladder in a 77-year-old woman who underwent renal biopsy and transurethral resection of the bladder tumor. Pathological examination revealed NEC in the kidney and the bladder samples. Immunohistochemical examination revealed strongly positive staining for synaptophysin, chromogranin A, and CD56, and focally positive staining for cytokeratin AE 1/3 and Cam 5.2. Fluorescence in situ hybridization confirmed the increased chromosome 3 copy number, and loss of hybridization in 3q21, 5q22-23, 10q26, and 13q14 was detected when the tumor samples were compared with normal samples. CONCLUSIONS: This is a rare case of NEC-specific genetic abnormalities in a kidney-derived tumor, and is the first report to identify kidney-derived NEC that metastasized to the bladder via the urinary tract. PMID- 26360823 TI - The signaling pathway involved in the proliferation of corneal endothelial cells. AB - Corneal transparency is maintained by the corneal endothelium through its barrier and ionic pump function. However, this function could be compromised with age and variety of diseases and trauma, leading to cornea dycompensation, corneal edema, bullous keratopathy and even loss of visual acuity. So far, a lot of measures have been proposed to solve the problem through promoting the corneal endothelial cells (CECs) proliferation both in vivo and in vitro. However, the exact molecular mechanism regarding the proliferation potential as well as associated phenotype maintenance of CECs has not been well clarified. Accordingly, we will review the studies outlined the signal transduction pathways that were involved in the process of CECs proliferation, which is an important and relatively seldom touched research direction for future new therapies of corneal endothelium dysfunction. By operating the crucial signaling molecular in these pathways, we anticipate to activate or block the signaling pathways and thus help engineering CEC monolayer for clinical transplantation. PMID- 26360824 TI - Scar-free cutaneous wound healing in the leopard gecko, Eublepharis macularius. AB - Cutaneous wounds heal with two possible outcomes: scarification or near-perfect integumentary restoration. Whereas scar formation has been intensively investigated, less is known about the tissue-level events characterising wounds that spontaneously heal scar-free, particularly in non-foetal amniotes. Here, a spatiotemporal investigation of scar-free cutaneous wound healing following full thickness excisional biopsies to the tail and body of leopard geckos (Eublepharis macularius) is provided. All injuries healed without scarring. Cutaneous repair involves the development of a cell-rich aggregate within the wound bed, similar to scarring wounds. Unlike scar formation, scar-free healing involves a more rapid closure of the wound epithelium, and a delay in blood vessel development and collagen deposition within the wound bed. It was found that, while granulation tissue of scarring wounds is hypervascular, scar-free wound healing conspicuously does not involve a period of exuberant blood vessel formation. In addition, during scar-free wound healing the newly formed blood vessels are typically perivascular cell-supported. Immunohistochemistry revealed widespread expression of both the pro-angiogenic factor vascular endothelial growth factor A and the anti-angiogenic factor thrombospondin-1 within the healing wound. It was found that scar-free wound healing is an intrinsic property of leopard gecko integument, and involves a modulation of the cutaneous scar repair program. This proportional revascularisation is an important factor in scar-free wound healing. PMID- 26360825 TI - The metabolic effects of a commercially available chicken peri-peri (African bird's eye chilli) meal in overweight individuals. AB - A growing body of evidence suggests that capsaicin ingestion may lead to desirable metabolic outcomes; however, the results in humans are equivocal. Whether or not benefits may be gained from ingestion of capsaicin via a commercially available meal has not been determined. The objectives of this randomised, cross-over intervention study were to compare the 2 h postprandial effects of a standard commercially prepared meal containing chilli (HOT, 5.82 mg total capsaicinoids) with a similar meal with no chilli (CON, 25 kg/m2 and a waist circumference >94 cm (men) or 80 cm (women), were studied. Participants had normal glucose tolerance and were accustomed, but were not regular chilli eaters. A paired t test indicated that insulin AUC was smaller following the HOT meal (P=0.002). Similarly, there was a tendency for glucose AUC to be reduced following the HOT meal (P=0.056). No discernable effects of the HOT meal were observed on metabolic rate, core temperature, hs-CRP concentrations and endothelial-dependent microvascular reactivity. The results from this study indicate that a standard restaurant meal containing a relatively small dose of capsaicin delivered via African bird's eye chilli, which is currently available to the public, results in lower postprandial insulin concentrations in overweight individuals, compared with the same meal without chilli. PMID- 26360826 TI - When Science Replaces Religion: Science as a Secular Authority Bolsters Moral Sensitivity. AB - Scientific and religious thinking compete with each other on several levels. For example, activating one generally weakens the other. Since priming religion is known to increase moral behaviour and moral sensitivity, priming science might be expected to have the opposite effect. However, it was recently demonstrated that, on the contrary, science priming increases moral sensitivity as well. The present set of studies sought to replicate this effect and test two explanations for it. Study 1 used a sentence unscrambling task for implicitly priming the concept of science but failed to replicate its effect on moral sensitivity, presumably due to a ceiling effect. Study 2 replicated the effect with a new measure of moral sensitivity. Study 3 tested whether science-related words create this effect by activating the idea of secular authority or by activating analytic thinking. It was demonstrated that words related to secular authority, but not words related to analytic thinking, produced a similar increase in moral sensitivity. Religiosity level of the participants did not influence this basic finding. The results are consistent with the hypothesis that science as a secular institution has overtaken some of the functions of religion in modern societies. PMID- 26360827 TI - Anatomical glenohumeral internal rotation deficit and symmetric rotational strength in male and female young beach volleyball players. AB - Beach volleyball is a sport with a high demand of shoulder structures that may lead to adaptations in range of motion (ROM) and strength like in other overhead sports. Despite of these possible alterations, no study evaluated the shoulder adaptations in young beach volleyball athletes. The aim of this study was to compare the bilateral ROM and rotation strength in the shoulders of young beach volleyball players. Goniometric passive shoulder ROM of motion and isometric rotational strength were evaluated in 19 male and 14 female asymptomatic athletes. External and internal ROM, total rotation motion, glenohumeral internal rotation deficit (GIRD), external rotation and internal rotation strength, bilateral deficits and external rotation to internal rotation ratio were measured. The statistical analysis included paired Student's t-test and analysis of variance with repeated measures. Significantly lower dominant GIRD was found in both groups (p<0.05), but only 6 athletes presented pathological GIRD. For strength variables, no significant differences for external or internal rotation were evident. Young beach volleyball athletes present symmetric rotational strength and shoulder ROM rotational adaptations that can be considered as anatomical. These results indicate that young practitioners of beach volleyball are subject to moderate adaptations compared to those reported for other overhead sports. PMID- 26360828 TI - Descriptive analysis of kinematics and kinetics of catchers throwing to second base from their knees. AB - In order to decrease the amount of time that it takes the catcher to throw the ball, a catcher may chose to throw from the knees. Upper extremity kinematics may play a significant role in the kinetics about the elbow observed in catchers throwing from the knees. If relationships between kinematics and kinetics exist then the development of training and coaching instruction may help in reduced upper extremity injury risk. Twenty-two baseball and softball catchers (14.36+/ 3.86years; 165.11+/-17.54cm; 65.67+/-20.60kg) volunteered. The catchers exhibited a less trunk rotation (5.6+/-16.2 degrees ), greater elbow flexion (87.9+/-21.4 degrees ) and decreased humeral elevation (71.1+/-12.3 degrees ) at the event of maximum shoulder external rotation as compared to what has previously reported in catchers. These variables are important, as they have previously been established as potential injury risk factors in pitchers, however it is not yet clear the role these variables play in catchers' risk of injury. A positive relationship between elbow varus torque during the deceleration phase and elbow flexion at MIR was observed (r=0.609; p=0.003). Throwing from the knees reduces a catcher's ability to utilize the proximal kinetic chain and this may help to explain why their kinematics and kinetics differ from what has previously been presented in the literature. PMID- 26360829 TI - The Relation between Obesity and Hospital Length of Stay after Elective Lateral Skull Base Surgery: An Analysis of the American College of Surgeons National Surgical Quality Improvement Program. AB - PURPOSE: Length of stay is a marker of quality and efficiency of health care delivery. The objective of this study was to identify preoperative, intraoperative, and postoperative variables that impact length of stay after lateral skull base surgery. Methods/Procedures: The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) databases from 2009 2012 were analyzed, and patients undergoing elective lateral skull base surgery for benign lesions of cranial nerves were identified. The primary outcome measure of interest was length of hospital stay. Protracted length of stay was defined as >=75th percentile of length of stay for all patients. The impact of demographic factors, intraoperative variables, and postoperative complications on length of stay was assessed. RESULTS: In total, 252 patients were included. Almost half of the patients (41.2%) were classified as obese (body mass index >=30). Patients who were obese had significantly longer lengths of stay (5.6 +/- 3.9 days) when compared to patients who were not obese (4.6 +/- 3.4 days, p = 0.006). Multivariate regression analysis demonstrated that operative time, reoperation within 30 days of initial surgery, and obesity were independent predictors for protracted length of stay. CONCLUSION: National multi-institutional data from the ACS-NSQIP suggest that operative time, reoperation, and obesity are predictors of longer hospital stays after lateral skull base approaches for benign cranial nerve neoplasms. PMID- 26360830 TI - Summarizing systematic reviews: methodological development, conduct and reporting of an umbrella review approach. AB - AIMS: With the increase in the number of systematic reviews available, a logical next step to provide decision makers in healthcare with the evidence they require has been the conduct of reviews of existing systematic reviews. Syntheses of existing systematic reviews are referred to by many different names, one of which is an umbrella review. An umbrella review allows the findings of reviews relevant to a review question to be compared and contrasted. An umbrella review's most characteristic feature is that this type of evidence synthesis only considers for inclusion the highest level of evidence, namely other systematic reviews and meta analyses. A methodology working group was formed by the Joanna Briggs Institute to develop methodological guidance for the conduct of an umbrella review, including diverse types of evidence, both quantitative and qualitative. The aim of this study is to describe the development and guidance for the conduct of an umbrella review. METHODS: Discussion and testing of the elements of methods for the conduct of an umbrella review were held over a 6-month period by members of a methodology working group. The working group comprised six participants who corresponded via teleconference, e-mail and face-to-face meeting during this development period. In October 2013, the methodology was presented in a workshop at the Joanna Briggs Institute Convention. Workshop participants, review authors and methodologists provided further testing, critique and feedback on the proposed methodology. RESULTS: This study describes the methodology and methods developed for the conduct of an umbrella review that includes published systematic reviews and meta-analyses as the analytical unit of the review. Details are provided regarding the essential elements of an umbrella review, including presentation of the review question in a Population, Intervention, Comparator, Outcome format, nuances of the inclusion criteria and search strategy. A critical appraisal tool with 10 questions to help assess risk of bias in systematic reviews and meta-analyses was also developed and tested. Relevant details to extract from included reviews and how to best present the findings of both quantitative and qualitative systematic reviews in a reader friendly format are provided. CONCLUSIONS: Umbrella reviews provide a ready means for decision makers in healthcare to gain a clear understanding of a broad topic area. The umbrella review methodology described here is the first to consider reviews that report other than quantitative evidence derived from randomized controlled trials. The methodology includes an easy to use and informative summary of evidence table to readily provide decision makers with the available, highest level of evidence relevant to the question posed. PMID- 26360831 TI - Biofilm-Forming Abilities of Listeria monocytogenes Serotypes Isolated from Different Sources. AB - A total of 98 previously characterized and serotyped L. monocytogenes strains, comprising 32 of 1/2a; 20 of 1/2b and 46 of 4b serotype, from clinical and food sources were studied for their capability to form a biofilm. The microtiter plate assay revealed 62 (63.26%) strains as weak, 27 (27.55%) strains as moderate, and 9 (9.18%) strains as strong biofilm formers. Among the strong biofilm formers, 6 strains were of serotype 1/2a and 3 strains were of serotype 1/2b. None of the strain from 4b serotype exhibited strong biofilm formation. No firm correlation (p = 0.015) was noticed between any serotype and respective biofilm formation ability. Electron microscopic studies showed that strong biofilm forming isolates could synthesize a biofilm within 24 h on surfaces important in food industries such as stainless steel, ceramic tiles, high-density polyethylene plastics, polyvinyl chloride pipes, and glass. Cell enumeration of strong, moderate, and weak biofilm was performed to determine if the number of cells correlated with the biofilm-forming capabilities of the isolates. Strong, moderate, and weak biofilm showed 570+/-127* 103 cells/cm2, 33+/-26* 103 cells/cm2, 5+/-3* 103 cells/cm2, respectively, indicating that the number of cells was directly proportional to the strength of the biofilm. The hydrophobicity index (HI) analysis revealed higher hydrophobicity with an increased biofilm formation. Fatty acid methyl esterase analysis revealed the amount of certain fatty acids such as iso-C15:0, anteiso-C15:0, and anteiso-C17:0 fatty acids correlated with the biofilm-forming capability of L. monocytogenes. This study showed that different strains of L. monocytogenes form biofilm of different intensities which did not completely correlate with their serotype; however, it correlated with the number of cells, hydrophobicity, and amount of certain fatty acids. PMID- 26360833 TI - Fitz-Hugh-Curtis syndrome in a 16-year-old female due to Ureaplasma urealyticum. PMID- 26360832 TI - Inhibition of IGF-1-Mediated Cellular Migration and Invasion by Migracin A in Ovarian Clear Cell Carcinoma Cells. AB - Previously we isolated migracin A from a Streptomyces culture filtrate as an inhibitor of cancer cell migration. In the present research, we found that migracin A inhibited migration and invasion of ovarian clear cell carcinoma ES-2 cells. In the course of our mechanistic study, migracin A was shown to enhance vasohibin-1 expression in an angiogenesis array. We also confirmed that it increased the mRNA expression of this protein. Moreover, overexpression of vasohibin-1 lowered the migration but not the invasion of ES-2 cells. Then, we looked for another target protein employing a motility array, and found that migracin A lowered the IGF-1 expression. Knockdown of IGF-1 by siRNA decreased the migration and invasion of ES-2 cells. Migracin A also decreased Akt phosphorylation involved in the downstream signaling. Crosstalk analysis indicated that overexpression of vasohibin-1 decreased the IGF-1 expression. On the other hand, it showed no direct anticancer activity in terms of the ES-2 growth in agar. Migracin A inhibited the migration and IGF-1 expression in not only ES-2 but also another ovarian clear cell carcinoma JHOC-5 cells. In addition, it also inhibited capillary tube formation of human umbilical vein endothelial cells. Since its cytotoxicity is very low, migracin A may be a candidate for an anti-metastasis agent not exhibiting prominent toxicity. PMID- 26360834 TI - Pharmacokinetics and bioequivalence evaluation of acamprosate calcium tablets in healthy Chinese volunteers. AB - BACKGROUND: Few pharmacokinetic data of acamprosate were available in Chinese population and no medication is approved for alcohol dependence in China. PURPOSE: 1. Investigate the pharmacokinetic properties of acamprosate calcium in healthy Chinese male volunteers on single- and multiple-dose administration. 2. Compare the bioequivalence of two formulations of acamprosate calcium tablets both under fasting and fed conditions. METHODS: This open-label, randomized study included 3 stages. In each stage, a 2-way crossover bioequivalence study was conducted to study the pharmacokinetic properties and bioequivalence of acamprosate calcium tablets on multiple dosing after standardized meals, single dosing under fasting conditions and fed conditions, respectively. The washout period between each treatment in a stage and between each stage was 1week. Plasma acamprosate calcium was quantified by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Tolerability was evaluated by monitoring adverse events, physical examinations, 12-lead ECG, and laboratory tests. RESULTS: Totally, 36 male subjects were enrolled in the study and all of them completed the whole 3 study stages. Main pharmacokinetic parameters of test and reference formulations were as follows: multiple dosing, Tmax 9.94+/-6.59 and 9.47+/-5.47h, Cmax 435.74+/-348.10 and 346.54+/-155.66ng.mL(-1), AUC0-t 8600.52+/ 5264.77 and 9315.10+/-6820.03ng.mL(-1).h, AUC0-infinity 8845.38+/-5838.18 and 9669.24+/-7326.53ng.mL(-1).h, t1/2 10.06+/-8.83 and 9.87+/-10.35h; single dosing under fasting conditions, Tmax 7.29+/-4.87 and 6.57+/-1.85h, Cmax 247.85+/-110.05 and 244.64+/-132.43ng.mL(-1), AUC0-t 3385.41+/-1418.92 and 3496.24+/ 1767.29ng.mL(-1).h, AUC0-infinity 3781.53+/-1556.96 and 3829.56+/-1981.25ng.mL( 1).h, t1/2 13.07+/-17.24 and 10.26+/-7.78h; single dosing under fed conditions, Tmax 17.72+/-9.42 and 19.50+/-9.84h, Cmax 183.90+/-74.52 and 168.14+/-60.67ng.mL( 1), AUC0-t 3181.71+/-1368.24 and 3575.11+/-1416.39ng.mL(-1).h, AUC0 infinity3442.39+/-2002.53 and 3624.44+/-1418.12ng.mL(-1).h, t1/2 8.76+/-12.28 and 6.67+/-4.84h, respectively. In all three stages, 90% CIs for the test/reference ratio of AUC0-t and AUC0-infinity were located within 80%-125%, 90% CI for Cmax was within 70%-143%. CONCLUSIONS: Similar pharmacokinetic results of acamprosate calcium tablets in healthy Chinese volunteers were found as those in Caucasic population. In all three stages, the two formulations met the regulatory criteria for bioequivalence. Chictr.org identifier: ChiCTR-TTRCC-14004853. PMID- 26360835 TI - Renal tubular secretion of pramipexole. AB - The dopamine agonist pramipexole is cleared predominantly by the kidney with a major contribution of active renal secretion. Previously the organic cation transporter 2 (OCT2) was shown to be involved in the uptake of pramipexole by renal tubular cells, while the mechanism underlying efflux into tubular lumen remains unclear. Cimetidine, a potent inhibitor of multidrug and toxin extrusion proteins 1 (MATE1) and 2-K (MATE2-K), decreases renal pramipexole clearance in humans. We hypothesized that, in addition to OCT2, pramipexole may be a substrate of MATE-mediated transport. Pramipexole uptake was investigated using MDCK or HEK cells overexpressing OCT2, MATE1 or MATE2-K and the respective vector controls (Co). Transcellular pramipexole transport was investigated in MDCK cells single- or double-transfected with OCT2 and/or MATE1 and in Co cells, separating a basal from an apical compartment in a model for renal tubular secretion. Pramipexole uptake was 1.6-, 1.1-, or 1.6-folds in cells overexpressing OCT2, MATE1 or MATE2 K, respectively as compared to Co cells (p<0.05). In transcellular transport experiments, intracellular pramipexole accumulation was 1.7-folds in MDCK-OCT2 (p<0.001), and transcellular pramipexole transport was 2.2- and 4.0-folds in MDCK MATE1 and MDCK-OCT2-MATE1 cells as compared to Co cells (p<0.001). Transcellular pramipexole transport was pH dependent and inhibited by cimetidine with IC50 values of 12MUM and 5.5MUM in MATE1 and OCT2-MATE1 cells, respectively. Taken together, coordinate activity of OCT2-mediated uptake and MATE-mediated efflux determines pramipexole renal secretion. Reduced OCT2 or MATE transport activity due to genetic variation or drug-drug interactions may affect pramipexole renal secretion. PMID- 26360836 TI - Identification and physicochemical characterization of caffeine-citric acid co crystal polymorphs. AB - The purpose of the present study was to identify a new caffeine-citric acid co crystal (CA-CI) polymorph and characterize three CA-CI polymorphs. The stability order among the three CA-CI polymorphs was also determined. One new and two known CA-CI polymorphs were prepared by the liquid-assisted grinding method or the slurry methods. The three CA-CIs were then identified and characterized by powder X-ray diffraction (PXRD), thermal analysis, IR spectroscopy, Raman spectroscopy, and dynamic vapor sorption (DVS). The stability order of the CA-CIs was determined by the slurry conversion method. Each CA-CI showed distinct PXRD, IR, Raman, and DVS data. The melting points of CA-CIs were 131 degrees C (a new form, Form III), 141 degrees C (Form I), and 160 degrees C (Form II). The order of thermodynamic stability was CA-CI Form II>CA-CI Form I>CA-CI Form III. CA-CI Forms I and II were relatively stable against humidity compared to CA, CI and CA CI Form III. PMID- 26360837 TI - Influence of genetic polymorphisms on the pharmacokinetics of celecoxib and its two main metabolites in healthy Chinese subjects. AB - Celecoxib is a selective cyclooxygenase-2 inhibitor used extensively for the treatment of rheumatism and osteoarthritis. The aim of this study was to evaluate the influence of the genetic polymorphisms of CYP2C9, CYP2D6 and CYP3A4 on the pharmacokinetics (PK) of celecoxib and its two main metabolites, hydroxyl celecoxib and carboxy-celecoxib, in healthy Chinese subjects, based on a bioequivalence study of celecoxib. This study was an open-label, two-period, crossover study. 52 healthy Chinese male subjects were recruited and were genotyped for CYP2C9*3, CYP2C9*13, CYP2D6*10 and CYP3A4*18 by using polymerase chain reactions (PCR). They were randomly divided into two groups and each group received either 200mg test formulation followed by reference formulation or vice versa with a one-week washout period. Safety and tolerability were monitored throughout the study and no severe adverse events were observed. Genotyping using PCR revealed that none of the subjects carried the CYP3A4*18 and CYP2C9*13. Therefore, the influence of the CYP2C9*3 and CYP2D6*10 on the PK of celecoxib and its metabolites in Chinese was studied. Compared with CYP2C9*1/*1 group, pharmacokinetic parameters of celecoxib such as AUC0-48 and Cmax was increased by 90.6% and 45.8%, the t1/2 was extended by 21.8% and the CL/F was decreased by 51.1% in CYP2C9*1/*3 group. In terms of hydroxy-celecoxib, compared with CYP2C9*1/*1 group, the Cmax was decreased by 17.2%, the t1/2 prolonged 42.1% in CYP2C9*1/*3 group. In terms of carboxy-celecoxib, the AUC0-48 was increased by 25.2%, the t1/2 prolonged 16.1% and the CL/F was decreased by 21.2% in CYP2C9*1/*3 group. Except for the t1/2 of hydroxy-celecoxib, no statistically significant difference was observed in other pharmacokinetic parameters of hydroxy-celecoxib and carboxy-celecoxib between the two CYP2C9 genotypic groups. This study revealed that there was no significant influence of CYP2D6*10 on the metabolism of celecoxib, and the expression of CYP2C9*3 led to increased drug exposure and slowed drug disposition in healthy Chinese male subjects. PMID- 26360838 TI - Feasibility of highly branched cyclic dextrin as an excipient matrix in dry powder inhalers. AB - We investigated the feasibility of highly branched cyclic dextrin (HBCD) as an excipient matrix in dry powder inhalers (DPIs). The fine particles of HBCD and HBCD/active pharmaceutical ingredients (APIs) were prepared by spray-drying an ethanol-aqueous solution containing HBCD. The particle size of spray-dried HBCD itself was approximately 3.0MUm with a wrinkled shape. Solid-state fluorescence emission spectroscopy of 1-naphthoic acid (1-NPA) showed that it was dispersed in a molecular dispersion/solid solution, if the model compound of 1-NPA was spray dried with HBCD. Powder X-ray diffraction and differential scanning calorimetry indicate that 1-NPA was in the amorphous state after spray-drying with HBCD, which is confirmed by the fluorescence measurements, 1-NPA could be incorporated into HBCD. When the antimycobacterial agent, rifampicin, was spray-dried with HBCD for the purpose of pulmonary administration, the emitted dose and fine particle fraction of the spray-dried particles of rifampicin with HBCD were 95.7+/-1.7% and 39.5+/-5.7%, respectively. The results indicated that HBCD possessed a high potential as an excipient in DPIs, not only by molecular association of API molecules with HBCD, but also by that of API fine crystals. PMID- 26360839 TI - Miniaturized INtrinsic DISsolution Screening (MINDISS) assay for preformulation. AB - This study describes a novel Miniaturized INtrinsic DISsolution Screening (MINDISS) assay for measuring disk intrinsic dissolution rates (DIDR). In MINDISS, compacted mini disks of drugs (2-5mg/disk) are prepared in custom made holders with a surface area of 3mm(2). Disks are immersed, pellet side down, into 0.35ml of appropriate dissolution media per well in 96-well microtiter plates, media are stirred and disk-holders are transferred to new wells after defined periods of time. After filtration, drug concentration in dissolution media is quantified by Ultra Performance Liquid Chromatography (UPLC) and solid state property of the disk is characterized by Raman spectroscopy. MINDISS was identified as an easy-to-use tool for rapid, parallel determination of DIDR of compounds that requires only small amounts of compound and of dissolution medium. Results obtained with marketed drugs in MINDISS correlate well with large scale DIDR methods and indicate that MINDISS can be used for (1) rank-ordering of compounds by intrinsic dissolution in late phase discovery and early development, (2) comparison of polymorphic forms and salts, (3) screening and selection of appropriate dissolution media, and (4) characterization of the intestinal release behavior of compounds along the gastro intestinal tract by changing biorelevant media during experiments. PMID- 26360841 TI - Duel diagnosis. PMID- 26360840 TI - Resveratrol-loaded liposomes for topical treatment of the vaginal inflammation and infections. AB - Resveratrol (RES), chemically known as 3,5,4'-trihydroxy-trans-stilbene, is a promising multi-targeted anti-oxidative and anti-inflammatory natural polyphenol. Preclinical studies showed its biological activities against the pathogens of sexually transmitted diseases causing vaginal inflammation and infections. Due to its low solubility and poor bioavailability, the optimal therapeutic uses are limited. Therefore, a clinically acceptable topical vaginal formulation of RES exhibiting optimal therapeutic effects is highly desirable. For this purpose, we prepared and optimized chitosan-coated liposomes with RES. The coated vesicles (mean diameter 200nm) entrapped up to 77% of RES, a sufficient load to assure required therapeutic outcome. In vitro drug release study showed the ability of liposomes to provide sustained release of RES. In vitro anti-oxidative activities of RES, namely DPPH and ABTS(*+) radicals scavenging assays, confirmed RES to be as potent as standard anti-oxidants, vitamins C and E. The anti-oxidative activities of RES and its corresponding liposomal formulation were also compared by measuring enhanced superoxide dismutase (SOD) activities in lipopolysaccharide (LPS)-induced J774A.1 cells. In vitro anti-inflammatory activities were compared by measuring nitric oxide (NO), tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta production in LPS-induced J774A.1 cells. Liposomal RES was found to exhibit stronger anti-oxidative and anti-inflammatory activities than RES solution. PMID- 26360842 TI - PTSD and DSM-5: unintended consequences of change. PMID- 26360843 TI - ADHD research: the power of population-based studies. PMID- 26360844 TI - Adolescent cannabis use and adverse sequelae in adulthood. PMID- 26360845 TI - Imaging brain circuits in anxiety disorders. PMID- 26360846 TI - There is no wealth without mental health. PMID- 26360847 TI - College mental health: a system in transition. PMID- 26360848 TI - WHO launches the first world suicide report. PMID- 26360850 TI - Corrections. PMID- 26360849 TI - Alienated alienists: a new hope? PMID- 26360851 TI - Mapping the psychocultural terrain with music. PMID- 26360852 TI - Mental health in Portugal in times of austerity. PMID- 26360854 TI - US authorities attempt to quantify ADHD prevalence in toddlers as treatment debate continues. PMID- 26360855 TI - Sharon Inouye. PMID- 26360856 TI - The sleeper must awaken: inside the mind of Dune. PMID- 26360857 TI - Forensic psychiatry: out of mind, out of sight. PMID- 26360858 TI - Hollow laughter. PMID- 26360859 TI - The kindness of strangers. PMID- 26360860 TI - The prevalence of post-traumatic stress disorder (PTSD) in US combat soldiers: a head-to-head comparison of DSM-5 versus DSM-IV-TR symptom criteria with the PTSD checklist. AB - BACKGROUND: The definition of post-traumatic stress disorder (PTSD) underwent substantial changes in the 2013 edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). How this will affect estimates of prevalence, whether clinical utility has been improved, and how many individuals who meet symptom criteria according to the previous definition will not meet new criteria is unknown. Updated screening instruments, including the PTSD checklist (PCL), have not been compared with previously validated methods through head-to-head comparisons. METHODS: We compared the new 20-item PCL, mapped to DSM-5 (PCL-5), with the original validated 17-item specific stressor version (PCL-S) in 1822 US infantry soldiers, including 946 soldiers who had been deployed to Iraq or Afghanistan. Surveys were administered in November, 2013. Soldiers alternately received either of two surveys that were identical except for the order of the two PCL versions (911 per group). Standardised scales measured major depression, generalised anxiety, alcohol misuse, and functional impairment. RESULTS: In analysis of all soldiers, 224 (13%) screened positive for PTSD by DSM-IV-TR criteria and 216 (12%) screened positive by DSM-5 criteria (kappa 0.67). In soldiers exposed to combat, 177 (19%) screened positive by DSM-IV-TR and 165 (18%) screened positive by DSM-5 criteria (0.66). However, of 221 soldiers with complete data who met DSM-IV-TR criteria, 67 (30%) did not meet DSM-5 criteria, and 59 additional soldiers met only DSM-5 criteria. PCL-5 scores from 15-38 performed similarly to PCL-S scores of 30-50; a PCL-5 score of 38 gave optimum agreement with a PCL-S of 50. The two definitions showed nearly identical association with other psychiatric disorders and functional impairment. CONCLUSIONS: Our findings showed the PCL-5 to be equivalent to the validated PCL S. However, the new PTSD symptom criteria do not seem to have greater clinical utility, and a high percentage of soldiers who met criteria by one definition did not meet the other criteria. Clinicians need to consider how to manage discordant outcomes, particularly for service members and veterans with PTSD who no longer meet criteria under DSM-5. FUNDING: US Army Military Operational Medicine Research Program (MOMRP), Fort Detrick, MD. PMID- 26360861 TI - Contact with the juvenile justice system in children treated with stimulant medication for attention deficit hyperactivity disorder: a population study. AB - BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is the most frequent neurodevelopmental disorder in children and is sometimes noted retrospectively in young people and adults who are incarcerated. We aimed to investigate juvenile justice encounters in children with and without ADHD. METHODS: Between January, 1995, and December, 2010, we did a population-based cohort study in Western Australia. Anonymised linked population data were obtained from the Western Australia Midwives Notification System. 12 831 non-Indigenous Australian children and young people aged 10-21 years, who were diagnosed and treated with stimulant drugs for ADHD and had a record in the Monitoring Drugs of Dependence System (ADHD cohort), were identified and frequency-matched by age, sex, and socioeconomic status to 29 722 non-Indigenous Australian children and young people who had no record in the Monitoring Drugs of Dependence System (controls). Community correction records and incarceration records were retrieved for all participants from Total Offending Management Solutions. Our primary outcome was to compare justice outcomes between children with ADHD and those without this disorder. We compared cohorts by conditional logistic regression analysis. FINDINGS: 9939 boys and 2892 girls were diagnosed and treated for ADHD; 22 875 boys and 6847 girls were frequency-matched controls. 792 (8%) boys and 75 (3%) girls with ADHD had a community correction record, compared with 822 (4%) boys and 75 (1%) girls without ADHD. 132 (1%) boys and 11 (<1%) girls with ADHD had an incarceration record, compared with 108 (<1%) boys and five (<1%) girls without ADHD. Compared with controls, boys with ADHD were two and half times more likely to have a community correction record (odds ratio 2.48, 95% CI 2.22-2.76) or an incarceration record (2.63, 2.01-3.44). Compared with their non-ADHD counterparts, girls with ADHD were nearly three times more likely to have a community correction record (odds ratio 2.86, 95% CI 2.03-4.03) and seven times more likely to have an incarceration record (7.27, 2.29-23.08). Boys with ADHD received their first community correction record at a younger age compared with controls (15.9 vs 16.3 years; p=0.0005), but age at first community correction record was similar for girls (16.5 vs 16.4 years; p=0.87). Burglaries and breaking and entering were the most common reason for a first justice record (total 659 [37%]), and this offence was twice as likely in children with ADHD (for boys, odds ratio 2.24, 95% CI 1.90-2.64; for girls, 2.19, 1.40-3.42). INTERPRETATION: Justice outcomes for boys and girls were more frequent among children and young people treated for ADHD compared with their non-ADHD counterparts. Unlike girls, boys were more likely to offend at a younger age. Early diagnosis and management of children and young people with ADHD might reduce the over-representation of children with this disorder within the juvenile justice system. FUNDING: National Health and Medical Research Council (Australia), Australian Research Council. PMID- 26360862 TI - Young adult sequelae of adolescent cannabis use: an integrative analysis. AB - BACKGROUND: Debate continues about the consequences of adolescent cannabis use. Existing data are limited in statistical power to examine rarer outcomes and less common, heavier patterns of cannabis use than those already investigated; furthermore, evidence has a piecemeal approach to reporting of young adult sequelae. We aimed to provide a broad picture of the psychosocial sequelae of adolescent cannabis use. METHODS: We integrated participant-level data from three large, long-running longitudinal studies from Australia and New Zealand: the Australian Temperament Project, the Christchurch Health and Development Study, and the Victorian Adolescent Health Cohort Study. We investigated the association between the maximum frequency of cannabis use before age 17 years (never, less than monthly, monthly or more, weekly or more, or daily) and seven developmental outcomes assessed up to age 30 years (high-school completion, attainment of university degree, cannabis dependence, use of other illicit drugs, suicide attempt, depression, and welfare dependence). The number of participants varied by outcome (N=2537 to N=3765). FINDINGS: We recorded clear and consistent associations and dose-response relations between the frequency of adolescent cannabis use and all adverse young adult outcomes. After covariate adjustment, compared with individuals who had never used cannabis, those who were daily users before age 17 years had clear reductions in the odds of high-school completion (adjusted odds ratio 0.37, 95% CI 0.20-0.66) and degree attainment (0.38, 0.22 0.66), and substantially increased odds of later cannabis dependence (17.95, 9.44 34.12), use of other illicit drugs (7.80, 4.46-13.63), and suicide attempt (6.83, 2.04-22.90). INTERPRETATION: Adverse sequelae of adolescent cannabis use are wide ranging and extend into young adulthood. Prevention or delay of cannabis use in adolescence is likely to have broad health and social benefits. Efforts to reform cannabis legislation should be carefully assessed to ensure they reduce adolescent cannabis use and prevent potentially adverse developmental effects. FUNDING: Australian Government National Health and Medical Research Council. PMID- 26360864 TI - Conflicted control systems: the neural architecture of trauma. PMID- 26360863 TI - Delirium and depression: inter-relationship and clinical overlap in elderly people. AB - Delirium and depression are complex neuropsychiatric syndromes common in the elderly and are associated with poor health-care outcomes. Accurate diagnosis is essential to the provision of optimum health care for individuals with these conditions but is complicated by substantial clinical overlap in symptoms and comorbidities. A careful assessment of the patient's symptoms, including their context and time course, is needed for accurate diagnosis. Previous depression is common in patients with delirium and depressive illness is a recognised sequelae of delirium. The two syndromes seem to be caused by similar pathophysiological mechanisms, involving disturbances in stress and inflammatory responses, monoaminergic and melatonergic signalling, which point to new avenues for therapeutic intervention. Improved methods to assess delirium and depression in populations at high risk by virtue of their age, diminished cognitive reserve and physical frailty is a key target to achieve improved health-care outcomes in elderly individuals. PMID- 26360865 TI - Corrections. PMID- 26360866 TI - Rights of people with mental illness. PMID- 26360867 TI - An alternative name for schizophrenia. PMID- 26360868 TI - An alternative name for schizophrenia. PMID- 26360869 TI - Editorial. PMID- 26360870 TI - Top value platform chemicals: bio-based production of organic acids. AB - Driven by the quest for sustainability, recent years have seen a tremendous progress in bio-based production routes from renewable raw materials to commercial goods. Particularly, the production of organic acids has crystallized as a competitive and fast-evolving field, related to the broad applicability of organic acids for direct use, as polymer building blocks, and as commodity chemicals. Here, we review recent advances in metabolic engineering and industrial market scenarios with focus on organic acids as top value products from biomass, accessible through fermentation and biotransformation. PMID- 26360871 TI - Heading in the right direction: thermodynamics-based network analysis and pathway engineering. AB - Thermodynamics-based network analysis through the introduction of thermodynamic constraints in metabolic models allows a deeper analysis of metabolism and guides pathway engineering. The number and the areas of applications of thermodynamics based network analysis methods have been increasing in the last ten years. We review recent applications of these methods and we identify the areas that such analysis can contribute significantly, and the needs for future developments. We find that organisms with multiple compartments and extremophiles present challenges for modeling and thermodynamics-based flux analysis. The evolution of current and new methods must also address the issues of the multiple alternatives in flux directionalities and the uncertainties and partial information from analytical methods. PMID- 26360872 TI - Phosphoketolase pathway engineering for carbon-efficient biocatalysis. AB - Recent advances in metabolic engineering have facilitated the development of microbial biocatalysts capable of producing an array of bio-products, ranging from fuels to drug molecules. These bio-products are commonly generated through an acetyl-CoA intermediate, which serves as a key precursor in the biological conversion of carbon substrates. Conventional biocatalytic upgrading strategies proceeding through this route are limited by low carbon efficiencies, in large part due to carbon losses associated with pyruvate decarboxylation to acetyl-CoA. Bypass of pyruvate decarboxylation offers a means to dramatically enhance carbon yields and, in turn, bioprocess economics. Herein, we discuss recent advances and prospects for employing the phosphoketolase pathway for direct biosynthesis of acetyl-CoA from carbon substrates, and phosphoketolase-based metabolic engineering strategies for carbon efficient biocatalysis. PMID- 26360873 TI - Cephalometry in adults and children with neurofibromatosis type 1: Implications for the pathogenesis of sphenoid wing dysplasia and the "NF1 facies". AB - BACKGROUND: Neurofibromatosis type 1 (NF1) is a common, autosomal dominant tumor predisposition disorder that arises secondary to mutations in the tumor suppressor gene NF1. Cephalometry is an inexpensive, readily available and non invasive technique that is under-utilized in studying the NF1 craniofacial phenotype. An analysis of NF1 cephalometry was first published by Heerva et al. in 2011. We expand here on that first investigation with a larger cohort of adult and pediatric patients affected with NF1 and sought objective insight into the NF1 facies, said to feature hypertelorism and a broad nasal base, from cephalometric analysis. METHODS: We obtained cephalograms from 101 patients with NF1 (78 adults and 23 children) from two NF1 protocols at the National Institutes of Health. Each subject had an age-, gender- and ethnicity-matched control. We used Dolphin software to make the cephalometric measurements. We assessed the normality of differences between paired samples using the Shapiro-Wilk test and evaluated the significance of mean differences using paired t-tests and adjusted for multiple testing. We explored the relationship between the cephalometric measurements and height, head circumference and interpupillary distance. RESULTS: In this dataset of American whites with NF1, we confirmed in a modestly larger sample many of the findings found by Heerva et al. in an NF1 Finnish cohort. We found a shorter maxilla, mandible, cranial base, (especially anteriorly, p = 0.0001) and diminished facial height in adults, but not children, with NF1. Only one adult exhibited hypertelorism. CONCLUSIONS: The cephalometric differences in adults arise in part from cranial base shortening and thus result in a shorter face, mid-face hypoplasia, reduced facial projection, smaller jaw, and increased braincase globularity. In addition, we suggest that NF1 sphenoid bone shortening, a common event, is consistent with an intrinsic NF1 bone cell defect, which renders the bone more vulnerable to a random "second hit" in NF1, leading to sphenoid wing dysplasia, a rare event. PMID- 26360874 TI - A novel mutation af Cln3 associated with delayed-classic juvenile ceroid lipofuscinois and autophagic vacuolar myopathy. AB - Juvenile neuronal-ceroid-lipofuscinosis (JNCL) is a lysosomal storage disease caused by mutations in CLN3. The most frequent mutation is a 1.02-kb deletion that, when homozygous, causes the classical clinical presentation. Patients harboring mutations different than the major deletion show a marked clinical heterogeneity, including protracted disease course with possible involvement of extraneuronal tissues. Cardiac involvement is relatively rare in JNCL and it is usually due to myocardial storage of ceroid-lipofuscinin. Only recently, histopathological findings of autophagic vacuolar myopathy (AVM) were detected in JNCL patients with severe cardiomyopathy. We describe a 35-year-old male showing a delayed-classic JNCL with visual loss in childhood and neurological manifestations only appearing in adult life. He had an unusual CLN3 genotype with an unreported deletion (p.Ala349_Leu350del) and the known p.His315Glnfs*67 mutation. Autophagic vacuolar myopathy was shown by muscle biopsy. At clinical follow-up, moderately increased CPK levels were detected whereas periodic cardiac assessments have been normal to date. Adult neurologists should be aware of protracted JNCL as cause of progressive neurological decline in adults. The occurrence of autophagic vacuolar myopathy necessitates periodic cardiac surveillance, which is not usually an issue in classic JNCL due to early neurological death. PMID- 26360875 TI - Alkane production from biomass: chemo-, bio- and integrated catalytic approaches. AB - Linear, branched and cyclic alkanes are important intermediates and end products of the chemical industry and are nowadays mainly obtained from fossil resources. In search for alternatives, biomass feedstocks are often presented as a renewable carbon source for the production of fuels, chemicals and materials. However, providing a complete market for all these applications seems unrealistic due to both financial and logistic issues. Despite the very large scale of current alkane-based fuel applications, biomass definitely has the potential to offer a partial solution to the fuel business. For the smaller market of chemicals and materials, a transition to biomass as main carbon source is more realistic and even probably unavoidable in the long term. The appropriate use and further development of integrated chemo- and biotechnological (catalytic) process strategies will be crucial to successfully accomplish this petro-to-bio feedstock transition. Furthermore, a selection of the most promising technologies from the available chemo- and biocatalytic tool box is presented. New opportunities will certainly arise when multidisciplinary approaches are further explored in the future. In an attempt to select the most appropriate biomass sources for each specific alkane-based application, a diagram inspired by van Krevelen is applied, taking into account both the C-number and the relative functionality of the product molecules. PMID- 26360876 TI - Microevolution of Aedes aegypti. AB - Scientific research into the epidemiology of dengue frequently focuses on the microevolution and dispersion of the mosquito Aedes aegypti. One of the world's largest urban agglomerations infested by Ae. aegypti is the Brazilian megalopolis of Sao Paulo, where >26,900 cases of dengue were reported until June 2015. Unfortunately, the dynamics of the genetic variability of Ae. aegypti in the Sao Paulo area have not been well studied. To reduce this knowledge gap, we assessed the morphogenetic variability of a population of Ae. aegypti from a densely urbanised neighbourhood of Sao Paulo. We tested if allelic patterns could vary over a short term and if wing shape could be a predictor of the genetic variation. Over a period of 14 months, we examined the variation of genetic (microsatellites loci) and morphological (wing geometry) markers in Ae. aegypti. Polymorphisms were detected, as revealed by the variability of 20 microsatellite loci (115 alleles combined; overall Fst = 0.0358) and 18 wing landmarks (quantitative estimator Qst = 0.4732). These levels of polymorphism are higher than typically expected to an exotic species. Allelic frequencies of the loci changed over time and temporal variation in the wing shape was even more pronounced, permitting high reclassification levels of chronological samples. In spite of the fact that both markers underwent temporal variation, no correlation was detected between their dynamics. We concluded that microevolution was detected despite the short observational period, but the intensities of change of the markers were discrepant. Wing shape failed from predicting allelic temporal variation. Possibly, natural selection (Qst>Fst) or variance of expressivity of wing phenotype are involved in this discrepancy. Other possibly influential factors on microevolution of Ae. aegypti are worth searching. Additionally, the implications of the rapid evolution and high polymorphism of this mosquito vector on the efficacy of control methods have yet to be investigated. PMID- 26360877 TI - Composition of Follow-Up Formula for Young Children Aged 12-36 Months: Recommendations of an International Expert Group Coordinated by the Nutrition Association of Thailand and the Early Nutrition Academy. AB - BACKGROUND: There are no internationally agreed recommendations on compositional requirements of follow-up formula for young children (FUF-YC) aged 1-3 years. AIM: The aim of the study is to propose international compositional recommendations for FUF-YC. METHODS: Compositional recommendations for FUF-YC were devised by expert consensus based on a detailed literature review of nutrient intakes and unmet needs in children aged 12-36 months. RESULTS AND CONCLUSIONS: Problematic nutrients with often inadequate intakes are the vitamins A, D, B12, C and folate, calcium, iron, iodine and zinc. If used, FUF-YC should be fed along with an age-appropriate mixed diet, usually contributing 1-2 cups (200-400 ml) of FUF-YC daily (approximately 15% of total energy intake). Protein from cow's milk-based formula should provide 1.6-2.7 g/100 kcal. Fat content should be 4.4-6.0 g/100 kcal. Carbohydrate should contribute 9-14 g/100 kcal with >50% from lactose. If other sugars are added, they should not exceed 10% of total carbohydrates. Calcium should provide 200 mg/100 kcal. Other micronutrient contents/100 kcal should reach 15% of the World Health Organization/Food and Agriculture Organization recommended nutrient intake values. A guidance upper level that was 3-5 times of the minimum level was established. Countries may adapt compositional requirements, considering recommended nutrient intakes, habitual diets, nutritional status and existence of micronutrient programs to ensure adequacy while preventing excessive intakes. PMID- 26360878 TI - Response to "Reply to the 'Comment on "Cholesterol Solubility Limit in Lipid Membranes probed by Small Angle Neutron Scattering and MD Simulations by Ursula Perez-Salas, Soft Matter, 2014, 10, 9313-9317"'". PMID- 26360880 TI - Short term supplementation rates to optimise vitamin E concentration for retail colour stability of Australian lamb meat. AB - The relationship between vitamin E supplementation rate and colour stability was investigated using 70 mixed sex 6-8 month old crossbred lambs. An initial group of 10 were slaughtered, while the remainder were fed a pellet ration containing either 30, 150, 275 or 400 IU vitamin E/kg ration or on green pasture for 56 days. After slaughter, carcases were halved; one side packed fresh (5 days) and the other in CO2 (21 days), both at 2 degrees C. Five muscles were set for retail display for 96 h. The oxy/metmyoglobin ratio was measured every 12 h. Colour stability increased with increasing muscle vitamin E until an apparent maximum effect for vitamin E concentration (3.5-4.0mg alpha-tocopherol/kg tissue) was reached beyond which no further response was evident. This was reached within 3-4 weeks (275 IU treatment), and meat from these lambs should reach 60 h retail display with a satisfactory surface colour. This effect was most apparent in aerobic muscle types and meat aged post slaughter. PMID- 26360881 TI - Tree Diversity Limits the Impact of an Invasive Forest Pest. AB - The impact of invasive herbivore species may be lower in more diverse plant communities due to mechanisms of associational resistance. According to the "resource concentration hypothesis" the amount and accessibility of host plants is reduced in diverse plant communities, thus limiting the exploitation of resources by consumers. In addition, the "natural enemy hypothesis" suggests that richer plant assemblages provide natural enemies with more complementary resources and habitats, thus promoting top down regulation of herbivores. We tested these two hypotheses by comparing crown damage by the invasive Asian chestnut gall wasp (Dryocosmus kuriphilus) on chestnut trees (Castanea sativa) in pure and mixed stands in Italy. We estimated the defoliation on 70 chestnut trees in 15 mature stands sampled in the same region along a gradient of tree species richness ranging from one species (chestnut monocultures) to four species (mixtures of chestnut and three broadleaved species). Chestnut defoliation was significantly lower in stands with higher tree diversity. Damage on individual chestnut trees decreased with increasing height of neighboring, heterospecific trees. These results suggest that conservation biological control method based on tree species mixtures might help to reduce the impact of the Asian chestnut gall. PMID- 26360879 TI - Staphylococcus aureus Inhibits IL-8 Responses Induced by Pseudomonas aeruginosa in Airway Epithelial Cells. AB - Pseudomonas aeruginosa (PA) and Staphylococcus aureus (SA) are major respiratory pathogens and can concurrently colonize the airways of patients with chronic obstructive diseases, such as cystic fibrosis (CF). Airway epithelial cell signalling is critical to the activation of innate immune responses. In the setting of polymicrobial colonization or infection of the respiratory tract, how epithelial cells integrate different bacterial stimuli remains unknown. Our study examined the inflammatory responses to PA and SA co-stimulations. Immortalised airway epithelial cells (Beas-2B) exposed to bacteria-free filtrates from PA (PAF) induced a robust production of the neutrophil chemoattractant IL-8 while bacteria-free filtrates from SA (SAF) had a minimal effect. Surprisingly, co stimulation with PAF+SAF demonstrated that SAF strongly inhibited the PAF-driven IL-8 production, showing that SAF has potent anti-inflammatory effects. Similarly SAF decreased IL-8 production induced by the TLR1/TLR2 ligand Pam3CysSK4 but not the TLR4 ligand LPS nor TLR5 ligand flagellin in Beas-2B cells. Moreover, SAF greatly dampened TLR1/TLR2-mediated activation of the NF-kappaB pathway, but not the p38 MAPK pathway. We observed this SAF-dependent anti-inflammatory activity in several SA clinical strains, as well as in the CF epithelial cell line CFBE41o . These findings show a novel direct anti-inflammatory effect of SA on airway epithelial cells, highlighting its potential to modulate inflammatory responses in the setting of polymicrobial infections. PMID- 26360882 TI - A 3D-Printed Oxygen Control Insert for a 24-Well Plate. AB - 3D printing has emerged as a method for directly printing complete microfluidic devices, although printing materials have been limited to oxygen-impermeable materials. We demonstrate the addition of gas permeable PDMS (Polydimethylsiloxane) membranes to 3D-printed microfluidic devices as a means to enable oxygen control cell culture studies. The incorporation of a 3D-printed device and gas-permeable membranes was demonstrated on a 24-well oxygen control device for standard multiwell plates. The direct printing allows integrated distribution channels and device geometries not possible with traditional planar lithography. With this device, four different oxygen conditions were able to be controlled, and six wells were maintained under each oxygen condition. We demonstrate enhanced transcription of the gene VEGFA (vascular endothelial growth factor A) with decreasing oxygen levels in human lung adenocarcinoma cells. This is the first 3D-printed device incorporating gas permeable membranes to facilitate oxygen control in cell culture. PMID- 26360883 TI - Multifaceted approach for the fabrication of metallomicelles and metallic nanoparticles using solvophobic bisdodecylaminepalladium (II) chloride as precursor. AB - A one-pot synthesis of solvophobic bisdodecylaminepalladium(II) chloride (complex 1) was performed. Complex 1 was characterized using X-ray crystallography and other techniques, namely, mass spectrometry, Fourier transform infrared, NMR, elemental analysis, etc. A multifaceted approach was taken to explore the potential applications of complex 1. The micellization ability of complex 1 was estimated using conductivity method in n-alcohols. The metallomicelles are formed in alcohols, and the process is thermodynamically spontaneous in nature. Using complex 1 as precursor, palladium (Pd) nanoparticles were fabricated using two phase redox method, where reduction is being performed in core of metallomicelles formed by complex 1 in dichloromethane (DCM). The micellization in DCM is confirmed by small-angle X-ray scattering (SAXS). The SAXS measurements reveal that the micellar of core 4-5 nm is being formed, which further controls the size of nanoparticle. This approach was advantageous in terms of size control, methodology, and yield. Pd nanoparticles were characterized using transmission electron microscopy, energy-dispersive X-ray spectroscopy, X-ray diffraction, and UV-visible spectroscopy and were also screened for bovine serum albumin interactions. Complex 1 and Pd nanoparticles were found to possess antimicrobial property with broad spectrum and are active against bacteria and fungi. The cytotoxicity analyses were performed over healthy cells (Vero cell lines extracted from kidney of green monkey), and the results reveal IC50 value of 10 MUg/mL for complex 1. PMID- 26360884 TI - Care for bipolar disorder in LMICs needs evidence from local settings. PMID- 26360885 TI - Advance care planning in dementia. PMID- 26360886 TI - Informed consent for psychotherapy: still not routine. PMID- 26360887 TI - Corrections. PMID- 26360888 TI - Corrections. PMID- 26360889 TI - Transition from adolescent to adult mental health services in Europe from the provider's perspective. PMID- 26360890 TI - Service user involvement in research. PMID- 26360892 TI - Merete Nordentoft: intervening early in mental illness. PMID- 26360893 TI - Ketamine for depression: the highs and lows. PMID- 26360894 TI - Beyond boundaries. PMID- 26360895 TI - Enlightenment: spiritual or rational? PMID- 26360901 TI - Detection and treatment of at-risk mental state for developing a first psychosis: making up the balance. AB - The at-risk mental state (ARMS) has been substantially researched and used as the basis for new clinical settings and strategies over the past two decades. However, it has also caused controversy and intense debate. In this Review, we assess available evidence and propose future directions. Accumulating research suggests that a blend of clinical staging and profiling, which naturally incorporates ARMS, might be a better guide for treatment of patients in different stages of psychiatric illness than the categorical DSM and ICD systems. Furthermore, clinical staging, with its emphasis on balancing risks and benefits, could help to prevent premature treatment or overtreatment with psychotropic drugs. Meta-analyses and reviews show that treatment of ARMS leads to a significant reduction in transition rate to a first psychosis. The debate about stigma associated with ARMS is based on scarce published work. The few studies that have been done suggest that stigma (including self-stigma) arises largely from negative societal views on psychiatric disorders and, depending on the setting and approach, not from engagement in treatment for ARMS per se. The evidence base suggests that definition of ARMS is an important step in implementation of clinical staging and profiling in psychiatry. However, more research across traditional diagnostic boundaries is needed to refine these clinical phenotypes and link them to biomarkers with the goal of personalised stepwise care. Health-system reform is overdue and a parallel process to support this approach is needed, which is similar to how physical forms of non communicable disease are treated. PMID- 26360902 TI - Neural origins of psychosocial functioning impairments in major depression. AB - Major depressive disorder, a complex neuropsychiatric condition, is associated with psychosocial functioning impairments that could become chronic even after symptoms remit. Social functioning impairments in patients could also pose coping difficulties to individuals around them. In this Personal View, we trace the potential neurobiological origins of these impairments down to three candidate domains-namely, social perception and emotion processing, motivation and reward value processing, and social decision making. We argue that the neural basis of abnormalities in these domains could be detectable at different temporal stages during social interactions (eg, before and after decision stages), particularly within frontomesolimbic networks (ie, frontostriatal and amygdala-striatal circuitries). We review some of the experimental designs used to probe these circuits and suggest novel, integrative approaches. We propose that an understanding of the interactions between these domains could provide valuable insights for the clinical stratification of major depressive disorder subtypes and might inform future developments of novel treatment options in return. PMID- 26360903 TI - Into the west: British Association of Psychopharmacology Summer Meeting 2015. PMID- 26360905 TI - Contamination of Phthalate Esters (PAEs) in Typical Wastewater-Irrigated Agricultural Soils in Hebei, North China. AB - The Wangyang River (WYR) basin is a typical wastewater irrigation area in Hebei Province, North China. This study investigated the concentration and distribution of six priority phthalate esters (PAEs) in the agricultural soils in this area. Thirty-nine soil samples (0-20 cm) were collected along the WYR to assess the PAE residues in soils. Results showed that PAEs are ubiquitous environmental contaminants in the topsoil obtained from the irrigation area. The concentrations of Sigma6PAEs range from 0.191 MUg g-1 dw to 0.457 MUg g-1 dw with an average value of 0.294 MUg g-1 dw. Di(2-ethylhexyl) phthalate (DEHP) and di-n-butyl phthalate (DnBP) are the dominant PAE species in the agricultural soils. Among the DEHP concentrations, the highest DEHP concentration was found at the sites close to the villages; this result suggested that dense anthropogenic activities and random garbage disposal in the rural area are possible sources of PAEs. The PAE concentrations were weakly and positively correlated with soil organic carbon and soil enzyme activities; thus, these factors can affect the distribution of PAEs. This study further showed that only dimethyl phthalate (DMP) concentrations exceeded the recommended allowable concentrations; no remediation measures are necessary to control the PAEs in the WYR area. However, the PAEs in the topsoil may pose a potential risk to the ecosystem and human health in this area. Therefore, the exacerbating PAE pollution should be addressed. PMID- 26360906 TI - The Conserved G-Protein Coupled Receptor FSHR-1 Regulates Protective Host Responses to Infection and Oxidative Stress. AB - The innate immune system's ability to sense an infection is critical so that it can rapidly respond if pathogenic microorganisms threaten the host, but otherwise maintain a quiescent baseline state to avoid causing damage to the host or to commensal microorganisms. One important mechanism for discriminating between pathogenic and non-pathogenic bacteria is the recognition of cellular damage caused by a pathogen during the course of infection. In Caenorhabditis elegans, the conserved G-protein coupled receptor FSHR-1 is an important constituent of the innate immune response. FSHR-1 activates the expression of antimicrobial infection response genes in infected worms and delays accumulation of the ingested pathogen Pseudomonas aeruginosa. FSHR-1 is central not only to the worm's survival of infection by multiple pathogens, but also to the worm's survival of xenobiotic cadmium and oxidative stresses. Infected worms produce reactive oxygen species to fight off the pathogens; FSHR-1 is required at the site of infection for the expression of detoxifying genes that protect the host from collateral damage caused by this defense response. Finally, the FSHR-1 pathway is important for the ability of worms to discriminate pathogenic from benign bacteria and subsequently initiate an aversive learning program that promotes selective pathogen avoidance. PMID- 26360907 TI - Brain regions involved in dispositional mindfulness during resting state and their relation with well-being. AB - Mindfulness can be viewed as an important dispositional characteristic that reflects the tendency to be mindful in daily life, which is beneficial for improving individuals' both hedonic and eudaimonic well-being. However, no study to date has examined the brain regions involved in individual differences in dispositional mindfulness during the resting state and its relation with hedonic and eudaimonic well-being. To investigate this issue, the present study employed resting-state functional magnetic resonance imaging (rs-fMRI) to evaluate the regional homogeneity (ReHo) that measures the local synchronization of spontaneous brain activity in a large sample. We found that dispositional mindfulness was positively associated with the ReHo in the left orbitofrontal cortex (OFC), left parahippocampal gyrus (PHG), and right insula implicated in emotion processing, body awareness, and self-referential processing, and negatively associated with the ReHo in right inferior frontal gyrus (IFG) implicated in response inhibition and attentional control. Furthermore, we found different neural associations with hedonic (i.e., positive and negative affect) and eudaimonic well-being (i.e., the meaningful and purposeful life). Specifically, the ReHo in the IFG predicted eudaimonic well-being whereas the OFC predicted positive affect, both of which were mediated by dispositional mindfulness. Taken together, our study provides the first evidence for linking individual differences in dispositional mindfulness to spontaneous brain activity and demonstrates that dispositional mindfulness engages multiple brain mechanisms that differentially influence hedonic and eudaimonic well-being. PMID- 26360908 TI - A high-throughput colorimetric assay for glucose detection based on glucose oxidase-catalyzed enlargement of gold nanoparticles. AB - We developed a simple high-throughput colorimetric assay to detect glucose based on the glucose oxidase (GOx)-catalysed enlargement of gold nanoparticles (AuNPs). Compared with the currently available glucose kit method, the AuNP-based assay provides higher clinical sensitivity at lower cost, indicating its great potential to be a powerful tool for clinical screening of glucose. PMID- 26360909 TI - VirtualMicroscopy: ultra-fast interactive microscopy of gigapixel/terapixel images over internet. AB - As digital imaging technology advances, gigapixel or terapixel super resolution microscopic images become available. We have built a real time virtual microscopy technique for interactive analysis of super high resolution microscopic images over internet on standard desktops, laptops or mobile devices. The presented virtual microscopy technique is demonstrated to perform as fast as using a microscopy locally without any delay to assess gigapixel ultra high resolution image data through wired or wireless internet by a Tablet or a standard PC. More importantly, the presented technology enables analysis of super high resolution microscopic image across sites and time and allows multi-person analysis at the same time, which greatly speed up data analysis process and reduces miscommunication among scientists and doctors. A web site has been created for illustration purposes. (http://www-o.ntust.edu.tw/~cweiwang/VirtualMicroscopy). PMID- 26360910 TI - Nano-socketed nickel particles with enhanced coking resistance grown in situ by redox exsolution. AB - Metal particles supported on oxide surfaces are used as catalysts for a wide variety of processes in the chemical and energy conversion industries. For catalytic applications, metal particles are generally formed on an oxide support by physical or chemical deposition, or less commonly by exsolution from it. Although fundamentally different, both methods might be assumed to produce morphologically and functionally similar particles. Here we show that unlike nickel particles deposited on perovskite oxides, exsolved analogues are socketed into the parent perovskite, leading to enhanced stability and a significant decrease in the propensity for hydrocarbon coking, indicative of a stronger metal oxide interface. In addition, we reveal key surface effects and defect interactions critical for future design of exsolution-based perovskite materials for catalytic and other functionalities. This study provides a new dimension for tailoring particle-substrate interactions in the context of increasing interest for emergent interfacial phenomena. PMID- 26360911 TI - Large-Scale Predictive Drug Safety: From Structural Alerts to Biological Mechanisms. AB - The recent explosion of data linking drugs, proteins, and pathways with safety events has promoted the development of integrative systems approaches to large scale predictive drug safety. The added value of such approaches is that, beyond the traditional identification of potentially labile chemical fragments for selected toxicity end points, they have the potential to provide mechanistic insights for a much larger and diverse set of safety events in a statistically sound nonsupervised manner, based on the similarity to drug classes, the interaction with secondary targets, and the interference with biological pathways. The combined identification of chemical and biological hazards enhances our ability to assess the safety risk of bioactive small molecules with higher confidence than that using structural alerts only. We are still a very long way from reliably predicting drug safety, but advances toward gaining a better understanding of the mechanisms leading to adverse outcomes represent a step forward in this direction. PMID- 26360913 TI - Long-term conditions and medically-unexplained symptoms: feasibility of cognitive behavioural interventions within the improving access to Psychological Therapies Programme. AB - BACKGROUND: Improving access to psychological therapies (IAPT) is a major programme in England to treat common mental health problems, mainly through cognitive behaviour therapy. In 2012, a Pathfinder scheme was launched to develop interventions for people with chronic physical health conditions or medically unexplained symptoms. AIM: This qualitative component of the evaluation investigated feasibility and acceptability of IAPT provision for people with enduring physical health problems. METHOD: Qualitative interviews were conducted with project leaders in all 14 Pathfinder sites. FINDINGS: Various therapeutic and training interventions were introduced. Most patients received low-intensity, structured therapy, with high-intensity input provided by some Pathfinders for complex cases. Whether the focus was on psychological symptoms or on broader well being, psychiatric terminology was avoided to improve utilisation. Participants perceived high satisfaction among service-users. Training needs were indicated for IAPT workers in this specialised work. CONCLUSIONS: Cognitive behaviour interventions appeared to be acceptable for people struggling with physical health problems. Robust outcome evidence will be pursued in Phase II. PMID- 26360912 TI - Evidence for Functionally Relevant Encounter Complexes in Nitrogenase Catalysis. AB - Nitrogenase is the only enzyme that can convert atmospheric dinitrogen (N2) into biologically usable ammonia (NH3). To achieve this multielectron redox process, the nitrogenase component proteins, MoFe-protein (MoFeP) and Fe-protein (FeP), repeatedly associate and dissociate in an ATP-dependent manner, where one electron is transferred from FeP to MoFeP per association. Here, we provide experimental evidence that encounter complexes between FeP and MoFeP play a functional role in nitrogenase catalysis. The encounter complexes are stabilized by electrostatic interactions involving a positively charged patch on the beta subunit of MoFeP. Three single mutations (betaAsn399Glu, betaLys400Glu, and betaArg401Glu) in this patch were generated in Azotobacter vinelandii MoFeP. All of the resulting variants displayed decreases in specific catalytic activity, with the betaK400E mutation showing the largest effect. As simulated by the Thorneley-Lowe kinetic scheme, this single mutation lowered the rate constant for FeP-MoFeP association 5-fold. We also found that the betaK400E mutation did not affect the coupling of ATP hydrolysis with electron transfer (ET) between FeP and MoFeP. These data suggest a mechanism where FeP initially forms encounter complexes on the MoFeP beta-subunit surface en route to the ATP-activated, ET competent complex over the alphabeta-interface. PMID- 26360914 TI - DNA methylation profiles distinguish different subtypes of gastroenteropancreatic neuroendocrine tumors. AB - AIM: Most studies have considered gastroenteropancreatic neuroendocrine tumors (GEP-NETs) as a homogenous group of samples or distinguish only gastrointestinal from pancreatic endocrine tumors. This article investigates if DNA methylation patterns could distinguish subtypes of GEP-NETs. MATERIALS & METHODS: The DNA methylation level of 807 cancer-related genes was investigated in insulinomas, gastrinomas, non-functioning pancreatic endocrine tumors and small intestine endocrine tumors. RESULTS: DNA methylation patterns were found to be tumor type specific for each of the pancreatic tumor subtypes and identified two distinct methylation-based groups in small intestine endocrine tumors. Differences of DNA methylation levels were validated by pyrosequencing for 20 candidate genes and correlated with differences at the transcriptional level for four candidate genes. CONCLUSION: The heterogeneity of DNA methylation patterns in the different subtypes of gastroenteropancreatic neuroendocrine tumors suggests different underlying pathways and, therefore, these tumors should be considered as distinct entities in molecular and clinical studies. PMID- 26360915 TI - "Coming out" as an alcoholic: how former problem drinkers negotiate disclosure of their nondrinking identity. AB - Although communication is critical for former problem drinkers to reject drinks, socialize with others, minimize stigma, and maintain their health and sobriety, recovering alcoholics' communication has not been examined beyond alcohol self help groups. Using a Communication Privacy Management framework and in-depth, semistructured interviews, this study examined how former problem drinkers negotiate the disclosure of their nondrinking status. As participants perceived not drinking in the United States as deviant and socially risky, the investigation found participants primarily concealed their nondrinking status in order to fit in. Participants enacted specific communicative behaviors to regulate their privacy boundaries, only disclosing their struggles with alcohol when benefits outweighed costs (e.g., inspiring others, maintaining sobriety, or building relationships). This study offers practical disclosure strategies for former problem drinkers to protect their private information, manage social interactions, and stay sober. PMID- 26360916 TI - Maternal and infant activity: Analytic approaches for the study of circadian rhythm. AB - The study of infant and mother circadian rhythm entails choice of instruments appropriate for use in the home environment as well as selection of analytic approach that characterizes circadian rhythm. While actigraphy monitoring suits the needs of home study, limited studies have examined mother and infant rhythm derived from actigraphy. Among this existing research a variety of analyses have been employed to characterize 24-h rhythm, reducing ability to evaluate and synthesize findings. Few studies have examined the correspondence of mother and infant circadian parameters for the most frequently cited approaches: cosinor, non-parametric circadian rhythm analysis (NPCRA), and autocorrelation function (ACF). The purpose of this research was to examine analytic approaches in the study of mother and infant circadian activity rhythm. Forty-three healthy mother and infant pairs were studied in the home environment over a 72h period at infant age 4, 8, and 12 weeks. Activity was recorded continuously using actigraphy monitors and mothers completed a diary. Parameters of circadian rhythm were generated from cosinor analysis, NPCRA, and ACF. The correlation among measures of rhythm center (cosinor mesor, NPCRA mid level), strength or fit of 24-h period (cosinor magnitude and R(2), NPCRA amplitude and relative amplitude (RA)), phase (cosinor acrophase, NPCRA M10 and L5 midpoint), and rhythm stability and variability (NPCRA interdaily stability (IS) and intradaily variability (IV), ACF) was assessed, and additionally the effect size (eta(2)) for change over time evaluated. Results suggest that cosinor analysis, NPCRA, and autocorrelation provide several comparable parameters of infant and maternal circadian rhythm center, fit, and phase. IS and IV were strongly correlated with the 24-h cycle fit. The circadian parameters analyzed offer separate insight into rhythm and differing effect size for the detection of change over time. Findings inform selection of analysis and circadian parameters in the study of maternal and infant activity rhythm. PMID- 26360917 TI - Financial and Economic Costs of the Elimination and Eradication of Onchocerciasis (River Blindness) in Africa. AB - BACKGROUND: Onchocerciasis (river blindness) is a parasitic disease transmitted by blackflies. Symptoms include severe itching, skin lesions, and vision impairment including blindness. More than 99% of all cases are concentrated in sub-Saharan Africa. Fortunately, vector control and community-directed treatment with ivermectin have significantly decreased morbidity, and the treatment goal is shifting from control to elimination in Africa. METHODS: We estimated financial resources and societal opportunity costs associated with scaling up community directed treatment with ivermectin and implementing surveillance and response systems in endemic African regions for alternative treatment goals--control, elimination, and eradication. We used a micro-costing approach that allows adjustment for time-variant resource utilization and for the heterogeneity in the demographic, epidemiological, and political situation. RESULTS: The elimination and eradication scenarios, which include scaling up treatments to hypo-endemic and operationally challenging areas at the latest by 2021 and implementing intensive surveillance, would allow savings of $1.5 billion and $1.6 billion over 2013-2045 as compared to the control scenario. Although the elimination and eradication scenarios would require higher surveillance costs ($215 million and $242 million) than the control scenario ($47 million), intensive surveillance would enable treatments to be safely stopped earlier, thereby saving unnecessary costs for prolonged treatments as in the control scenario lacking such surveillance and response systems. CONCLUSIONS: The elimination and eradication of onchocerciasis are predicted to allow substantial cost-savings in the long run. To realize cost-savings, policymakers should keep empowering community volunteers, and pharmaceutical companies would need to continue drug donation. To sustain high surveillance costs required for elimination and eradication, endemic countries would need to enhance their domestic funding capacity. Societal and political will would be critical to sustaining all of these efforts in the long term. PMID- 26360918 TI - Mammography Decision Aid Reduces Decisional Conflict for Women in Their Forties Considering Screening. AB - BACKGROUND: Clinical guidelines recommend a personalized approach to mammography screening for women in their forties; however, methods to do so are lacking. An evidence-based mammography screening decision aid was developed as an electronic mobile application and evaluated in a before-after study. METHODS: The decision aid (Mammopad) included modules on breast cancer, mammography, risk assessment, and priority setting about screening. Women aged 40-49 years who were patients of rural primary care clinics, had no major risk factors for breast cancer, and no mammography during the previous year were invited to use the decision aid. Twenty women participated in pretesting of the decision aid and 75 additional women completed the before-after study. The primary outcome was decisional conflict measured before and after using Mammopad. Secondary outcomes included decision self-efficacy and intention to begin or continue mammography screening. Differences comparing measures before versus after use were determined using Wilcoxon signed rank tests. RESULTS: After using Mammopad, women reported reduced decisional conflict based on mean Decisional Conflict Scale scores overall (46.33 versus 8.33; Z = -7.225; p < 0.001) and on all subscales (p < 0.001). Women also reported increased mean Decision Self-Efficacy Scale scores (79.67 versus 95.73; Z = 6.816, p < 0.001). Although 19% of women changed their screening intentions, this was not statistically significant. CONCLUSIONS: Women reported less conflict about their decisions for mammography screening, and felt more confident to make decisions after using Mammopad. This approach may help guide women through the decision making process to determine personalized screening choices that are appropriate for them. PMID- 26360919 TI - The treatment of cancer-associated venous thromboembolism in the era of the novel oral anticoagulants. AB - INTRODUCTION: The initial and long-term administration of low-molecular-weight heparin (LMWH) is now regarded as the treatment of choice for the therapy of patients with cancer-associated venous thromboembolism (CAT). However, LMWH requires daily subcutaneous injections and can induce thrombocytopenia. In recent years, novel direct oral anticoagulants (DOAC) have emerged to potentially replace conventional treatments. AREAS COVERED: The advantages and limitations of conventional approaches for the treatment of CAT are presented and analyzed based on available findings and on recommendations from international guidelines, as is the potential for the DOAC. EXPERT OPINION: LMWH still remains the mainstay of initial and long-term treatment of CAT. Vitamin K antagonists may have a role in patients with inactive cancer and in those with severe renal failure. Whether there is a potential for the DOAC is uncertain. Indeed, most patients with advanced cancer were excluded from the trials addressing their value. Although available findings are encouraging, before implementing them in the routine clinical practice there is the need for dedicated studies in which cancer patients, whichever their severity and prognosis, are allocated to either DOAC or LMWH, which represent the standard of treatment for patients with CAT. PMID- 26360920 TI - Establishing a reentry procedure for human immunodeficiency virus screening reactive donors in China. AB - BACKGROUND: Screening of blood donors for antibody to human immunodeficiency virus Types 1 and 2 (anti-HIV-1/2) and/or HIV nucleic acid test (NAT) is a well established venue to prevent HIV transfusion-transmitted disease. However, with the current available technologies, HIV testing may result in donor loss due to false-positive results. This study intended to establish a donor reentry procedure for HIV screening-reactive donors in China. STUDY DESIGN AND METHODS: From September 1, 2013, to August 31, 2014, a total of 465 donors from 14 Chinese blood centers were enrolled in this study. Enrollment criteria include all donors who were screened reactive or belonged to the "gray zone" by enzyme-linked immunosorbent assay and/or reactive by NAT when tested at the local blood centers. All donor samples were sent to a central HIV confirmation laboratory where anti-HIV-1/2 and HIV individual-donation NATs were conducted. If the results were reactive for anti-HIV-1/2, then the samples were tested with a recombinant immunoblot assay. RESULTS: Based on the repeat testing at the central HIV confirmation laboratory 8 or 16 weeks after the study, 252 donors of 465 (54.2%) who completed the study could be classified in two categories for HIV status: 45 (18%) true positive and 207 (82%) false positive. A total of 213 of 465 (45.8%) donors were lost on follow-up and, thus, their HIV status cannot be determined with certainty. Based on these data, a donor reentry procedure was proposed. CONCLUSION: Based on our proposed donor reentry procedure for HIV screening-reactive donors, a majority of screening-positive donors (82%, 207/252) can be reentered safely. PMID- 26360922 TI - Maintaining Research Integrity While Balancing Cultural Sensitivity: A Case Study and Lessons From the Field. AB - Contemporary emphasis on creating culturally relevant and context specific knowledge increasingly drives researchers to conduct their work in settings outside their home country. This often requires researchers to build relationships with various stakeholders who may have a vested interest in the research. This case study examines the tension between relationship development with stakeholders and maintaining study integrity, in the context of potential harms, data credibility and cultural sensitivity. We describe an ethical breach in the conduct of global health research by a arising from the ad-hoc participation of a community stakeholder external to the visiting research group. A framework for reflection is developed from a careful examination of underlying factors and presented with a discussion of consequences and mitigation measures. This framework aims to present lessons learned for researchers working abroad who might face similar situations in their work. PMID- 26360921 TI - Hypothermia for preventing chemotherapy-induced neuropathy - a pilot study on safety and tolerability in healthy controls. AB - INTRODUCTION: Chemotherapy-induced peripheral neuropathy (CIPN) is a major dose limiting side effect of several chemotherapeutic agents, often leading to treatment discontinuation. Up to 20% of patients treated with weekly paclitaxel experience severe CIPN and no effective treatment has been established so far. The mechanisms of CIPN damage are unclear, but are directly dose-related. We had earlier demonstrated, in rats, the influence of hypothermia in reducing nerve blood flow. Here, we hypothesize that continuous flow limb hypothermia during chemotherapy reduces the incidence and severity of CIPN, by limiting deliverance of the neurotoxic drug to the peripheral nerves. In this study, prior to assessing the effect of hypothermia in preventing CIPN in cancer subjects undergoing paclitaxel chemotherapy, we assess the safety and tolerable temperatures for limb hypothermia in healthy human subjects. MATERIAL AND METHODS: In 15 healthy human subjects, hypothermia was administered as continuous flow cooling, unilaterally, via a thermoregulator setup covering the digits up to the elbow/knee, along with continuous skin temperature monitoring. Thermoregulator coolant temperatures between 25 degrees C and 20 degrees C were tested for tolerability, based on a carefully designed temperature regulation protocol, and maintained for three hours mimicking the duration of chemotherapy. Tolerability was evaluated using various safety and tolerability scores to monitor the subjects. RESULTS: At the end of the cooling session the healthy subjects presented without significant adverse effects, the main being brief mild skin erythema and transient numbness. Coolant temperatures as low as 22 degrees C were well tolerated continuously over three hours. CONCLUSION: Our results confirm the safety and tolerability of continuous flow limb hypothermia in healthy subjects. Further studies will use 22 degrees C thermoregulator temperature to investigate hypothermia in preventing CIPN in breast cancer patients receiving adjuvant weekly paclitaxel. This pilot study may contribute to alleviating chemotherapy dose limitation due to CIPN and increase the likelihood of success of chemotherapy. PMID- 26360923 TI - C-reactive Protein: Repeated Measurements will Improve Dialysis Patient Care. AB - Systemic inflammation is a common feature in the uremic phenotype and associates with poor outcomes. The awareness regarding the importance of inflammation assessment in chronic kidney disease (CKD) patients has risen in recent years, and despite the development of novel biomarkers, C-reactive protein (CRP) is still the most measured inflammatory parameter. Notwithstanding, the possible weak points of CRP determination, this biomarker has demonstrated being useful both for guidance in clinical practice and for risk estimation. In addition, regular determination of CRP among dialysis patients has been associated with better outcomes in different dialysis facilities. Because persistent inflammation may be a silent reflection of various pathophysiologic alterations in CKD, it is crucial that inflammatory markers are regularly monitored and therapeutic attempts be made to target this inflammation. PMID- 26360924 TI - Implicit measures of beliefs about sport ability in swimming and basketball. AB - Sport ability may be seen as relatively stable, genetically determined and not easily modified by practice, or as increasable with training, work and effort. Using the Implicit Association Test (IAT), the purpose of the present study is to examine whether the practice of a particular sport (swimming or basketball) can influence automatic beliefs about sport ability in these two sports. The IAT scores evidence that swimmers and basketball players automatically and implicitly associate their own sport with training rather than genetics, whereas non sportspersons have no significant automatic association. This result is strengthened when perceived competence and intrinsic motivation in swimming or basketball are high. PMID- 26360925 TI - The detection of a synthetic Interleukin-1 receptor antagonist peptide in a seized product from a racing stable. AB - A synthetic Interleukin-1 receptor antagonist peptide with the sequence Acetyl Phe-Glu-Trp-Thr-Pro-Gly-Tyr-Trp-Gln-Pro-Tyr-Ala-Leu-Pro-Leu-OH has been identified in a vial seized during a stable inspection. The use of peptide-based Interleukin-1 receptor antagonists as anti-inflammatory agents has not been previously reported, making this peptide the first in a new class of sports doping peptides. The peptide has been characterized by high-resolution mass spectrometry and a detection method developed based on solid-phase extraction and liquid chromatography - triple quadrupole mass spectrometry. Using in vitro and in vivo models to study the properties of the peptide after administration, the peptide was shown to be highly unstable in plasma and was not detected in urine after administration in a rat. The poor stability of the peptide makes detection challenging but also suggests that it has limited effectiveness as an anti inflammatory drug. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26360926 TI - Prevalence of soft tissue injuries in pediatric patients and its relationship with the quest for treatment. AB - BACKGROUND/AIM: Soft tissue injuries (STI) are common in children and adolescents. This retrospective study evaluated the frequency of STI, gender, type of injury, and its location in pediatric patients, comparing the different age groups and how the presence of these lesions influences the pursuit for immediate care. MATERIAL AND METHODS: Medical records of patients 0-15 years old who had been treated between 2005 and 2013 at the Dental Trauma Surveillance Center, School of Dentistry, Universidade Federal do Rio de Janeiro were included in this study. Records with incomplete data and those in which the patient took more than 2 weeks to seek attendance were excluded. The data collected included the age and gender of the patient, the frequency, type and location of the injury, and immediate treatment (<24 h). Data were analyzed descriptively and with the chi-square test (P <= 0.05). RESULTS: Of the 543 patients who met the eligibility criteria, 56.2% had STI, and males (65.6%), and the age group of 0-3 years (39.7%) were the most affected. The concomitant presence of lesions in the intra- and extra-oral region was the most frequent in all age groups. In the extra-oral region, contusion (20.7%) and abrasion (19.3%) were more common to the upper lip and laceration to the lower lip (18.4%). In the intra-oral region, the injury was more frequent to the gums (41%), while the lips were the most affected by abrasion (12.2%) and laceration (24.9%). Regardless of the age groups, the pursuit for immediate care was statistically influenced by the presence of soft tissue lesions (P < 0.05). CONCLUSION: We conclude that there is a high prevalence of STI in the study sample; the lesions were more common in boys and in patients aged 0-3 years. The presence of STI proved to be a determining factor for the pursuit for immediate care. PMID- 26360927 TI - Network meta-analysis with integrated nested Laplace approximations. AB - Analyzing the collected evidence of a systematic review in form of a network meta analysis (NMA) enjoys increasing popularity and provides a valuable instrument for decision making. Bayesian inference of NMA models is often propagated, especially if correlated random effects for multiarm trials are included. The standard choice for Bayesian inference is Markov chain Monte Carlo (MCMC) sampling, which is computationally intensive. An alternative to MCMC sampling is the recently suggested approximate Bayesian method of integrated nested Laplace approximations (INLA) that dramatically saves computation time without any substantial loss in accuracy. We show how INLA apply to NMA models for summary level as well as trial-arm level data. Specifically, we outline the modeling of multiarm trials and inference for functional contrasts with INLA. We demonstrate how INLA facilitate the assessment of network inconsistency with node-splitting. Three applications illustrate the use of INLA for a NMA. PMID- 26360928 TI - Chemical composition of the essential oil of Kaliphora madagascariensis Hook. f. AB - Kaliphora madagascariensis is an evergreen shrub or small tree endemic to Madagascar where it is traditionally used for the treatment of persistent cephalalgia by a strong inhalation of its odour. In this work, we analysed for the first time the essential oil obtained from leaves by Gas Chromatography-Mass Spectrometry. The chemical composition was dominated by oxygenated sesquiterpenes (68.1%), with caryophyllene oxide (14.7%) and beta-eudesmol (10.7%) as the most abundant constituents. These compounds are endowed with documented healthy effects such as analgesic, anti-inflammatory, neuritogenic, antiepileptic and hypotensive, and its abundance might explain the traditional use of the plant in Madagascar. PMID- 26360929 TI - Manganese-Catalyzed Direct Nucleophilic C(sp(2))-H Addition to Aldehydes and Nitriles. AB - Herein, a manganese-catalyzed nucleophilic addition of inert C(sp(2))-H bonds to aldehydes and nitriles is disclosed by virtue of a dual activation strategy. The reactions feature mild reaction conditions, excellent regio- and stereoselectivity, and a wide substrate scope, which includes both aromatic and olefinic C-H bonds, as well as a large variety of aldehydes and nitriles. Moreover, mechanistic studies shed light on possible catalytic cycles. PMID- 26360930 TI - Multicomponent Reaction of Z-Chlorooximes, Isocyanides, and Hydroxylamines as Hypernucleophilic Traps. A One-Pot Route to Aminodioximes and Their Transformation into 5-Amino-1,2,4-oxadiazoles by Mitsunobu-Beckmann Rearrangement. AB - Synthetically useful aminodioximes are prepared via a novel three-component reaction among Z-chlorooximes, isocyanides, and hydroxylamines by exploiting the preferential attack of isocyanides to nitrile N-oxides via a [3 + 1] cycloaddition reaction. The results of quantum mechanical studies of the reaction mechanism are also discussed. Furthermore, the one-pot conversion of aminodioximes to 1,2,3-oxadiazole-5-amines via Mitsunobu-Beckmann rearrangement is reported for the first time. PMID- 26360931 TI - Prescription Opioid Misuse, Abuse, Morbidity, and Mortality: Balancing Effective Pain Management and Safety. AB - OBJECTIVE: The burgeoning rate of prescription opioid misuse, abuse, addiction, and opioid related overdose deaths has gained substantial professional and national media attention. This manuscript provides a narrative review and critique of the literature on prescription opioid misuse, abuse, addiction and opioid-related mortality and discusses future research needs in this area. DESIGN: Current literature on misuse, abuse, addiction and opioid related fatalities was reviewed in patients with chronic noncancer pain receiving long term prescription opioid therapy. RESULTS: There have been inconclusive results on the efficacy of long-term opioid therapy in patients with chronic pain but moderate level evidence of dose-dependent risk of harm. The estimated prevalence of prescription opioid abuse and opioid use disorders ranges from <1% to 40% due to the paucity of uniform definitions of what constitutes misuse, abuse, and addiction but several recent studies have developed unique methodology to more accurately assess these states in the pain population. The rate of opioid-related overdose deaths is not inconsequential and a number of patient related and medication specific risk factors have been identified that may provide a basis for risk mitigation strategies. CONCLUSIONS: Accurately assessing the prevalence of misuse, abuse, and addiction in the pain population has been challenging due to inconsistent definitions between studies. Additional high-quality research is needed in this area utilizing consistent definitions and in reducing the risk of opioid-related overdose fatalities. PMID- 26360933 TI - Upregulation of MiR-122 via Trichostatin A Treatments in Hepatocyte-like Cells Derived from Mesenchymal Stem Cells. AB - The miR-122 is a tissue-specific miRNA; its expression is abundant in liver. MiR 122 upregulation is crucial for differentiation, functionality, and maintenance of differentiated phenotype in hepatocytes. The improving effects of trichostatin A (TSA) on hepatic differentiation have been reported previously. The aim of this study was to determine whether TSA can affect the expression of miR-122 in hepatocyte-like cells (HLCs) generated from human adipose tissue-derived mesenchymal stem cells (hAT-MSCs). The hepatic differentiation of hAT-MSCs induced by a mixture of growth factors and cytokines either with or without TSA treatments. The functionality of HLCs generated with or without TSA and the expression levels of miR-122 were studied. The expression levels of miR-122 in TSA-treated HLCs was significantly (p < 0.05) higher than those generated by growth factors and cytokines, only. The downregulation of a-fetoprotein (AFP) levels but enhanced albumin synthesis (p < 0.05) and upregulation of liver enriched transcription factors (LETFs) HNF4alpha (hepatocyte nuclear factor 4alpha) and HNF6 (hepatocyte nuclear factor 6) were observed in TSA-treated HLCs (p < 0.05). In conclusion, administration of TSA in hepatogenic differentiation of hAT-MSCs resulted in higher expression levels of miR-122, facilitation of differentiation, and subsequently attenuation of AFP levels. PMID- 26360932 TI - Quantitative determination of pravastatin and its metabolite 3alpha-hydroxy pravastatin in plasma and urine of pregnant patients by LC-MS/MS. AB - This report describes the development and validation of a chromatography/tandem mass spectrometry method for the quantitative determination of pravastatin and its metabolite (3alpha-hydroxy pravastatin) in plasma and urine of pregnant patients under treatment with pravastatin, as part of a clinical trial. The method includes a one-step sample preparation by liquid-liquid extraction. The extraction recovery of the analytes ranged between 93.8 and 99.5% in plasma. The lower limits of quantitation of the analytes in plasma samples were 0.106 ng/mL for pravastatin and 0.105 ng/mL for 3alpha-hydroxy pravastatin, while in urine samples they were 19.7 ng/mL for pravastatin and 2.00 ng/mL for 3alpha-hydroxy pravastatin. The relative deviation of this method was <10% for intra- and interday assays in plasma and urine samples, and the accuracy ranged between 97.2 and 106% in plasma, and between 98.2 and 105% in urine. The method described in this report was successfully utilized for determining the pharmacokinetics of pravastatin in pregnant patients enrolled in a pilot clinical trial for prevention of preeclampsia. PMID- 26360934 TI - Cancer caregiver quality of life: need for targeted intervention. AB - OBJECTIVES: Caregiving can negatively impact well-being. Cancer caregivers face unique challenges given the intense nature of cancer and treatment, which increases their risk for burden, poor quality of life (QOL), and burnout. Studies to reduce caregiver burden demonstrate QOL improvement and distress reduction in the short term. However, few studies exist to address long-term benefits. We assessed changes in various QOL domains after participation in a QOL intervention for caregivers of patients having newly diagnosed advanced cancer. METHODS: Our institutional review board-approved study randomized patient-caregiver dyads to either usual care or an in-person group intervention composed of six 90-min sessions of structured multidisciplinary QOL components delivered over 4 weeks, with 10 follow-up phone calls within 20 weeks. Caregivers attended four of the six sessions attended by patients. Sessions included physical therapy, coping and communication strategies, mental health education, spirituality, and social needs. Caregiver QOL (Caregiver Quality of Life Index-Cancer Scale [CQOLC] and Linear Analogue Self-Assessment [LASA]) and mood (Profile of Mood States-Brief [POMS-B]) were measured at baseline and 4, 27, and 52 weeks. Wilcoxon tests and effect sizes were used to compare the caregiver groups. RESULTS: Of the 131 caregivers (65 intervention and 66 usual care), 116 completed the study. Caregivers post-intervention (at 4 weeks) had improved scores on LASA Spiritual Well-being; POMS-B total score, Vigor/Activity, and Fatigue/Inertia; and CQOLC Adaptation. At long term (at 27 weeks), caregivers retained improvement in POMS-B Fatigue/Inertia and gained improvements in CQOLC Disruptiveness and Financial Concerns. CONCLUSIONS: Caregivers who received the intervention had higher QOL ratings for specific QOL domains but not for overall QOL. Although a comprehensive intervention was helpful, more specific, targeted interventions tailored for individual needs are recommended. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26360935 TI - Investigation of the Storage Behavior of Shredded Lithium-Ion Batteries from Electric Vehicles for Recycling Purposes. AB - Shredding of the cells is often the first step in lithium-ion battery (LIB) recycling. Thus, LiNi1/3 Mn1/3 Co1/3 O2 (NMC)/graphite lithium-ion cells from a field-tested electric vehicle were shredded and transferred to tinplate or plastic storage containers. The formation of hazardous compounds within, and being released from, these containers was monitored over 20 months. The tinplate cans underwent fast corrosion as a result of either residual charge in the active battery material, which could not fully be discharged because of contact loss to the current collector, or redox reactions between the tinplate surface and metal parts of the shredded material. The headspace compositions of the containers were investigated at room temperature and 150 degrees C using headspace-gas chromatography-mass spectrometry (HS-GC-MS). Samples of the waste material were also collected using microwave-assisted extraction and the extracts were analyzed over a period of 20 months using ion chromatography-electrospray ionization-mass spectrometry (IC-ESI-MS). LiPF6 was identified as a conducting salt, whereas dimethyl carbonate, ethyl methyl carbonate, and ethylene carbonate were the main solvent components. Cyclohexylbenzene was also detected, which is an additive for overcharge protection. Diethyl carbonate, fluoride, difluorophosphate and several ionic and non-ionic alkyl (fluoro)phosphates were also identified. Importantly, dimethyl fluorophosphate (DMFP) and diethyl fluorophosphate (DEFP) were quantified using HS-GC-MS through the use of an internal standard. DMFP, DEFP, and related compounds are known as chemical warfare agents, and the presence of these materials is of great interest. In the case of this study, these hazardous materials are present but in manageable low concentrations. Nonetheless, the presence of such compounds and their potential release during an accident that may occur during shredding or recycling of large amounts of LIB waste should be considered. PMID- 26360936 TI - A self-assembled nanotube for the direct aldol reaction in water. AB - Nanotubes formed by the aqueous assembly of a proline-lysine dipeptide (1) were used to create the hydrophobic microenvironments required to catalyze the aldol reaction in water. The self-assembly process occurred most efficiently in the presence of the substrates, producing an array of homogeneous nanotubes under the reaction conditions. The nanotubes formed by dipeptide 1 served as an efficient catalyst for the aldol reaction that functioned at low loading levels and provided good to excellent conversions. The catalytic activity of 1 was minimal under conditions that dissociated the nanotube into soluble monomers. PMID- 26360937 TI - Extra-fine particle inhaled corticosteroids, pharma-cokinetics and systemic activity in children with asthma. AB - During recent years, extra-fine particle inhaled corticosteroids with a median aerodynamic diameter <=2 MUm have been introduced in the treatment of asthma. The aim of this paper was to review pharmacokinetics and systemic activity of extra fine particle hydroalkane pressurized metered dose inhaled (pMDI) ciclesonide and beclomethasone dipropionate in children. A literature review was performed. Systemic bioavailability of oral and pulmonary deposition of extra-fine ciclesonide and beclomethasone dipropionate was 52% and 82%, the half-life in serum 3.2 and 1.5 h and first-pass hepatic metabolism >99% and 60%, respectively. Secondary analyses of urine cortisol/creatinine excretion found no effects of ciclesonide pMDI between 40 and 320 MUg/day or of beclomethasone dipropionate pMDI between 80 and 400 MUg/day. Ciclesonide pMDI 40, 80 and 160 MUg/day caused no effects on short-term lower leg growth rate as assessed by knemometry. Ciclesonide 320 MUg/day was associated with a numerically short-term growth suppression equivalent to 30% which was similar to 25% and 36% suppression caused by beclomethasone dipropionate HFA and CFC 200 MUg/day, respectively. Consistent with the differences in key pharmacokinetic features, beclomethasone dipropionate is associated with a systemic activity detected by knemometry at a lower dose than ciclesonide. Whether that correlates with a clinically important difference remains to be explored. Assessments of systemic activity of beclomethasone dipropionate <200 MUg/day and of ciclesonide >180 MUg/day as well as head-to-head comparisons are warranted. Preferably, such studies should apply the sensitive method of knemometry. PMID- 26360938 TI - [Atypical ECG - technical pitfalls]. PMID- 26360939 TI - [Atypical ECG - technical pitfalls]. PMID- 26360940 TI - [HIV-infection: Early therapy is beneficial]. PMID- 26360941 TI - [Fever, skin changes, myalgia - from early symptom to diagnosis]. PMID- 26360942 TI - [Liraglutid can support weight loss]. PMID- 26360943 TI - [Antidepressants for cancer patients: an individual decision]. PMID- 26360944 TI - [55-year old man with dyspnea]. PMID- 26360945 TI - [Diverticular disease: an everyday problem in a new light]. PMID- 26360946 TI - [Diverticular disease - new insights into pathogenesis]. AB - Diverticular disease is associated with a high incidence, morbidity and burden of the healthcare system. However, the pathogenesis is not yet satisfactorily clarified and thought to be multifactorial. Non-influenceable risk factors include increasing age, genetic predisposition and rare congenital connective tissue diseases. Influenceable risk factors are low-fiber diet, increased meat consumption and obesity. Alterations of connective tissue lead to a weakening of preformed emergence sites of diverticula ("loci minoris resistentiae") and may explain the increased incidence of diverticular disease in diseases caused by a systematic connective tissue disorder. The impact of neuromuscular alterations and disturbed colonic motility on triggering diverticula formation has been previously underestimated. Moreover, intestinal innervation disorders are considered to be responsable for persisting recurrent pain symptoms in chronic diverticular disease. PMID- 26360947 TI - [Diverticular disease - clinical patterns and treatment]. AB - Diverticulosis, diverticular disease and diverticulitis have come into focus again because new aspects concerning diagnosis, risk factors and treatment arose only recently which prompted a new Guideline released by the DGVS and DGAV summarising the current evidence. Along with the guideline's essentials for medical practice a diagnosis of diverticulitis is considered unsatisfactory unless a cross-sectional imaging method (either ultrasonography [US] or computed tomography [CT] ) has proven that the clinical findings and inflammation (CRP considered superior to WBC and temperature) are due to diverticular inflammation. For reasons of practicability and considering relevant legislation for radiation exposure protection, US is the primary - and usually effectual - diagnostic method of choice as it is equipotent to CT. While US offers better resolution and enables precise imaging exactly at the location of pain as well as reiterative application, the latter implies advantages in the case of a deep abscess or diverticulitis in difficult locations (e. g. the small pelvis). Clinical evidence and laboratory and imaging findings allow for distinguishing a large number of differential diagnoses and also form the basis of a new classification (classification of diverticular disease, CDD) which comprises all forms of diverticular disease, from diverticulosis to bleeding and to the different facettes of diverticulitis. This classification -which should be applied in any patient with the diagnosis of diverticular disease- is independent of specific diagnostic preferences and applicable both to conservative and operative treatment options. While the number of recurrent episodes is no longer a significant indicator for surgery in diverticulitis, severity and / or complications determine treatment options along with the patients preferences. According to first data, conservative treatment may waive antibiotics under certain circumstances, however they are indispensible in complicated disease or patients bearing risk factors. Spasmoanalgetics and supportive fluid supply are individually necessary, and avoidance of potentially aggravating medications (e. g. NSAIDS) appears advisable, but many suggestions (nil by mouth, bed rest, laxatives) come along without an adaequate body of evidence. Similarly medical advice concerning prevention and secondary prophylaxis relies mainly on epidemiological plausibility. Because minor perforations (CDD type 2 a) as well as recurrent episodes of uncomplicated diverticulitis and even some abscesses > 1 cm (CDD type 2 b) respond favourably to medical treatment, the timely indication for surgery in these cases requires precise classification along with a close surveillance in trustful cooperation between the gastroenterologist and the surgeon. PMID- 26360948 TI - [Diverticular disease - timing of surgery in demand]. AB - In preparation for operations of patients with diverticular disease an adequate medical indication has to be performed. The new classification of sigmoid diverticulitis corresponding to the German guidelines for diverticular disease classification (GGDDC) enables an appropriate strategy for evaluating the indications and selection of the time for surgery. New is, that the uncomplicated form of diverticulitis indicates an operation in exceptional case only. Furthermore the frequency of diverticulitis-exacerbation does not influence the indication for surgery any more. PMID- 26360949 TI - [What do I have to do to start my clinical study?]. AB - "What do I have to do to start my clinical study" is one question often asked by physicians new to the field of medical research. Even many experienced researchers are challenged by this question given the complex and rapidly changing legal and regulatory aspects of clinical studies. In this article we will offer a guide to the planning of your clinical study. PMID- 26360950 TI - [Renal artery intervention in the post-CORAL era - obsolete or sometimes reasonable?]. AB - Significant renal artery stenosis may cause both secondary therapy-resistant arterial hypertension and renal failure. We report the case of a 74-year old man with an occlusion of the right renal artery and a stenosis of the left renal artery causing right sided renal atrophy, renal failure and resistant arterial hypertension. Revascularization with percutaneous renal angioplasty (PTRA)/stenting of the left renal artery helped to improve both kidney function and hypertension control. Interestingly, the patient would not have qualified for any of the recent randomized outcome trials. Therefore, renal artery intervention remains a reasonable option in highly and interdisciplinarily selected patients, despite the more conservative treatment approach after the recent trials. PMID- 26360951 TI - [Right-sided laptop dermatitis]. AB - HISTORY AND CLINICAL FINDINGS: A 44-year-old man presented at a dermatologist with a 2 months history of a blue-brown reticular macule on the right thigh that had appeared spontaneously. It was neither painful nor itching and showed no growth or further colour change. INVESTIGATIONS: Punch biopsy, antinuclear antibodies, CrP, immune electrophoresis, hepatitis serology, urine diagnostics showed normal results. DIAGNOSIS: On specific inquiry the patient, a long distance truck driver, reported to rest his laptop during driving breaks always on the right thigh. We diagnosed a "laptop dermatitis". CONCLUSION: Consider external mechanical or thermal triggers if skin changes are unilateral. Thermal isolation from permanent heat exposure prevents an erythema ab igne reliably. PMID- 26360952 TI - [Polypharmacy in the elderly - choosing wisely by using the FORTA list]. AB - Multimorbidity and polypharmacy are threats to elderly patients; improvement of medication is important and a novel listing approach - the FORTA [Fit fOR The Aged] list - should support this in clinical practice. Here, we aim to describe procedural details of successful application of FORTA. FORTA labels range from A (indispensable), B (beneficial), C (questionable) to D (avoid), depending on evidence for safety, efficacy and overall age-appropriateness. As an implicit tool, it is only applicable if medical details of the patient are known. The process starts with history taking and diagnostic assessment including disease grading. This is the base for FORTA-assisted selection of drugs to avoid overtreatment (drug not necessary), undertreatment (condition not or not sufficiently treated by positively labeled drugs) or mistreatment (drugs indicated, but negatively rather than positively labeled drug chosen). Selection is followed by secondary analyses, e. g. regarding dosing or contraindications. The medication scheme is updated in reflection of wanted clinical effects (e. g. blood pressure lowering) and side effects (e. g. dizziness). PMID- 26360953 TI - [Participation of hospital nephrology departments in outpatient dialysis care. Joint Statement of the "Deutsche Gesellschaft fur Nephrologie (DGfN)", "Verband leitender Klinikarzte in der Nephrologie (VLKN)", "Verband Deutsche Nierenzentren (DN) e. V." , "KfH Kuratorium fur Dialyse und Nierentransplantation e. V." and "PHV - Der Dialysepartner Patienten-Heimversorgung"]. AB - The proposals by health care providers to impose drastic limits on chronic dialysis in hospitals to the extent that it can only be provided on loss-making terms, will jeopardize the cost efficiency of nephrological departments in hospitals and hence their continued existence. Such departments play a key role within the discipline, however, as the training of nephrologists is tied to them by further training regulations. The authors take the view that the proposals by health care providers are short-sighted with regard to the quality of care and the safeguarding of care in the future, and that they counteract the goals of quality assurance currently dominating the health policy agenda. PMID- 26360954 TI - [Sex differences in infectious diseases and their clinical consequences]. AB - Differences between women and men range from their anatomy, their natural social behavior to their susceptibility and response to different pathologies, including infectious diseases. The underlying mechanisms of sex differences in infectious diseases are manifold, including differences in exposure to common pathogens, genetic factors that modulate immune responses against pathogens and hormonal factors that may alter susceptibility or disease progression, and responsiveness to treatment. On one hand, these mechanisms lead to higher innate and adaptive immune responses in females, which result in faster clearance of acute infections and higher antibody responses to several vaccines, on the other hand this contributes to an increased susceptibility to chronic inflammatory diseases. In this review we summarize the underlying causes of sex differences in prevalence, clinical course of disease and treatment outcome of infectious diseases. In order to develop individualized treatment concepts, a fair balance between the sexes should be maintained in basic science, preclinical and clinical studies. PMID- 26360955 TI - [Cross-sectional study of satisfaction with studies and lifestyle among medical students in Austria, Germany and Switzerland]. AB - BACKGROUND: The aim was to examine potential differences in various aspects of life as well as study satisfaction amongst medical students of three German speaking countries. METHOD: Data was collected between February and June 2010 using an online survey with the open source survey tool Limesurvey (Version 1.85 RC3). RESULTS: 1179 medical students in year 4-6 completed the online questionnaire (798 in Germany (Ger), 265 in Austria (A) and 116 in Switzerland (CH)). Mean age was similar (25.0-25.3) for the countries (p = 0.14). Respondents from Austria were significantly more often (17.4 %) smoking than Swiss (12.1 %) or German (10 %) medical students (p = 0.002). The average number of hours spent studying per week and desired weekly work hours varied significantly between countries. The average desired working week post-graduation was 42 hours. The perceived ability to work as junior doctor post-graduation was below 5 on a visual analogue scale of 1-10. CONCLUSION: Results of consumption, work life balance and activity were similar to statistics of the population of each country. With regard to the desired work time after graduation this is in clear contrast to the reality as a doctor. Improvement of medical courses can be achieved with better preparation for the internship. PMID- 26360956 TI - [Role of Institutional Review Boards for multi-centre studies in national health services research - a cross-sectional study of the effort to obtain secondary ethical approvals for the DACAPO study]. AB - BACKGROUND: Health services research (HSR) is of fundamental importance for the continuous improvement of preventive, diagnostic or therapeutic measures. The conduct of multi-centre HSR studies requires that ethical approval by Institutional review boards (IRB's) is obtained. We documented the effort, the complexity and the man power necessary to obtain secondary ethical approval for a national HSR in Germany ("Surviving the Acute Respiratory Distress Syndrome" [DACAPO-study]). METHODS: Having obtained a primary ethical approval by the IRB of Regensburg University, the time, correspondence, necessity for amendments, corrections, or additional costs by 34 IRB's for 64 participating study centers was documented. RESULTS: The complete obtainment was found to be time consuming and associated with a high workload and man power. A time span of seven month was needed to receive votes from all IRB's. The median time span was 25,5 days (25 %/75 % percentile 13 and 42 days, respectively). Requirements in terms of corrections or amendments were inhomogeneous and frequent changes were necessary. There were additional fees for secondary votes of 4328,40 ?. Total costs for the study center Regensburg were 21.193,40 ? (2,6 % of the grant volume). CONCLUSION: Obtaining all ethical approvals for a multi-centre observational HSR study in Germany is complex and time consuming. Various and inhomogeneous formalities may delay the plan and realization of HSR. A Homogenization and simplification of the procedure of ethics votes should be discussed. PMID- 26360957 TI - Assessment of Confabulation in Patients with Alcohol-Related Cognitive Disorders: The Nijmegen-Venray Confabulation List (NVCL-20). AB - OBJECTIVE: Even though the first awareness of confabulations is often based on observations, only questionnaires and structured interviews quantifying provoked confabulations are available. So far, no tools have been developed to measure spontaneous confabulation. This study describes and validates an observation scale for quantifying confabulation behavior, including spontaneous confabulations, in clinical practice. METHOD: An observation scale consisting of 20 items was developed, the Nijmegen-Venray Confabulation List-20 (NVCL-20). This scale covers spontaneous confabulation, provoked confabulation, and memory and orientation. Professional caregivers completed the NVCL-20 for 28 Korsakoff (KS) patients and 24 cognitively impaired chronic alcoholics (ALC). Their ratings were related to the Dalla Barba Confabulation Battery (DBCB), Provoked Confabulation Test (PCT), and standard neuropsychological tests. RESULTS: The categories of the NVCL-20 have "good" to "excellent" internal consistency and inter-rater agreement. The KS patients confabulated more (both spontaneously and provoked), and more memory and orientation problems were observed. Correlations with neuropsychological test scores showed that confabulations were associated with memory deficits, but not with intrusions or tests of executive dysfunction. CONCLUSIONS: The NVCL-20 is the first instrument that includes items addressing spontaneous confabulation. Administration is reliable, valid and feasible in clinical practice, making it a useful addition to existing confabulating measures. PMID- 26360958 TI - Transient twin reversed arterial perfusion: a protective effect in twin-to-twin transfusion syndrome? PMID- 26360959 TI - Copper-Catalyzed Cyanation of Aryl- and Alkenylboronic Reagents with Cyanogen Iodide. AB - Direct catalytic cyanation of organoboronic acids with cyanogen iodide has been achieved by using a copper-bipyridine catalyst system. The cyanation reaction is likely to occur through two catalytic cycles: copper(II)-catalyzed iodination of organoboronic acids and the following cyanidocopper(I)-mediated cyanation of organic iodides. PMID- 26360961 TI - Kinetically Controlled Growth of Fine Gold Nanofractals from Au(I) via Indirect Galvanic Replacement Reaction. AB - Two of the most important features of Au nanostructures, size and shape, are significantly affected by the reduction kinetics of the relevant metal precursors. Because of the high standard oxidative potential of gold ionic species, AuCl4(-) in particular, Au fractals formed via various chemical or electrochemical approaches often have very coarse branches with diameters varying from tens of nanometers to submicrometers, even though extensive chemicals and/or complicated processes have been deployed to control the reduction kinetics. Herein we report an indirect galvanic replacement (IGR) strategy where the electrons generated in a galvanic replacement reaction from anode oxidation are channeled out to a separate conducting film on which the cathodic metal can be deposited. Reduction of Au(I) ionic species with relatively low standard oxidative potential has been conducted with the IGR experimental setting. 2D finely hyperbranched Au fractals (4.0 nm in diameter and a few micrometers in length) with high structural integrity were produced. Controls over the deposition density, location, and microfeatures of Au nanofractals were demonstrated through a mechanistic study. In addition, the thus-prepared Au nanofractals were also thoroughly tested in electrochemical sensing of H2O2. PMID- 26360960 TI - Is There Evidence for Systematic Upcoding of ASA Physical Status Coincident with Payer Incentives? A Regression Discontinuity Analysis of the National Anesthesia Clinical Outcomes Registry. AB - BACKGROUND: Modifications in physician billing patterns have been shown to occur in response to payer incentives, but the phenomenon remains largely unexplored in billing for anesthesia services. Within the field of anesthesiology, Medicare's policy not to provide additional reimbursement for higher ASA physical status scores contrasts with the practices of most private payers, and this pattern of reimbursement introduces a change in billing incentives once patients attain Medicare eligibility. We hypothesized that, coincident with the onset of widespread Medicare eligibility at age 65 years, a discontinuity in reported ASA physical status scores would be observed after controlling for the underlying trend of increasing ASA physical status scores with age. This phenomenon would manifest as a pattern of upcoding of ASA physical status scores for patients younger than 65 years that would become less common in patients age 65 years and older. METHODS: Using data on age, sex, ASA physical status scores, and type of surgery from the National Anesthesia Clinical Outcomes Registry, we used a quasi experimental regression discontinuity design to analyze whether there was evidence for a discontinuity in reported ASA physical status scores occurring at age 65 years for the nondeferrable anesthesia services accompanying hip, femur, or lower leg fracture repair. RESULTS: A total of 49,850 records were analyzed. In models designed to detect regression discontinuity at 65 years of age, neither the binary variable "age >= 65" nor the interaction term of age * age >= 65 was a statistically significant predictor of the outcome of ASA physical status score. The statistical inference was unchanged when ASA physical status scores were reclassified as a binary outcome (I-II vs III-V) and when different bandwidths around age 65 years were used. To test the validity of our study design for detecting regression discontinuity, simulations of the occurrence of deliberate upcoding of ASA physical status scores demonstrated the ability to detect deliberate upcoding occurring at rates exceeding 2% of eligible cases of patients younger than 65 years. CONCLUSIONS: We found no evidence for a significant discontinuity in the pattern of ASA physical status scores coincident with Medicare eligibility at age 65 years for the nondeferrable conditions of hip, femur, or lower leg fracture repair. Our data do not support the presence of fraudulent ASA physical status scoring among National Anesthesia Clinical Outcomes Registry contributors. If deliberate upcoding of ASA physical status scores is present in our data, the behavior is either too rare or too insensitive to the removal of payer incentives at age 65 years to be evident in the present analysis. PMID- 26360962 TI - Comparison of Cardiorespiratory and Metabolic Responses in Kettlebell High Intensity Interval Training Versus Sprint Interval Cycling. AB - The purpose of this study was to determine the effectiveness of a novel exercise protocol we developed for kettlebell high-intensity interval training (KB-HIIT) by comparing the cardiorespiratory and metabolic responses to a standard sprint interval cycling (SIC) exercise protocol. Eight men volunteered for the study and completed 2 preliminary sessions, followed by two 12-minute sessions of KB-HIIT and SIC in a counterbalanced fashion. In the KB-HITT session, 3 circuits of 4 exercises were performed using a Tabata regimen. In the SIC session, three 30 second sprints were performed, with 4 minutes of recovery in between the first 2 sprints and 2.5 minutes of recovery after the last sprint. A within-subjects' design over multiple time points was used to compare oxygen consumption (V[Combining Dot Above]O2), respiratory exchange ratio (RER), tidal volume (TV), breathing frequency (f), minute ventilation (VE), caloric expenditure rate (kcal.min), and heart rate (HR) between the exercise protocols. Additionally, total caloric expenditure was compared. A significant group effect, time effect, and group * time interaction were found for V[Combining Dot Above]O2, RER, and TV, with V[Combining Dot Above]O2 being higher and TV and RER being lower in the KB-HIIT compared with the SIC. Only a significant time effect and group * time interaction were found for f, VE, kcal.min, and HR. Additionally, total caloric expenditure was found to be significantly higher during the KB-HIIT. The results of this study suggest that KB-HIIT may be more attractive and sustainable than SIC and can be effective in stimulating cardiorespiratory and metabolic responses that could improve health and aerobic performance. PMID- 26360963 TI - Opioid Use and Risk of Nonvertebral Fractures in Adults With Rheumatoid Arthritis: A Nested Case-Control Study Using Administrative Databases. AB - OBJECTIVE: To assess the risk of nonvertebral fractures in patients with rheumatoid arthritis (RA) who were exposed to opioids. METHODS: A population based, nested case-control study was conducted using health services administrative databases (Quebec, Canada) from 1997 to 2012. Among RA patients, cases of nonvertebral fractures from 2007 to 2012 were identified using a validated algorithm. The date of the first fracture was the index date for the case and his/her matched control. Controls were selected using incidence density sampling and were matched 5:1 to cases for age, sex, and date of RA diagnosis. Opioid exposure was classified as current use, recent past use, remote past use, and nonuse. Conditional logistic regression was used to assess the association of nonvertebral fractures with opioid exposure, adjusting for comorbidity, indicators of RA severity, drugs influencing fracture risk, and health care utilization. RESULTS: In total, 1,723 cases and 8,046 controls were identified. Among these patients, 2,595 (722 cases and 1,873 controls) had been exposed to opioids. Current use (versus nonuse) increased the risk of nonvertebral fracture. Cumulative current use of opioids according to the quartile distribution was also associated with the risk of nonvertebral fracture: for continuous use for 1-20 days before the index date, odds ratio (OR) 11.49 (95% confidence interval [95% CI] 8.81-14.99); for 21-155 days, OR 1.75 (95% CI 1.31-2.33); for 156-355 days, OR 1.54 (95% CI 1.17-2.04); and for >=356 days, OR 1.73 (95% CI 1.31-2.30). No association between the risk of nonvertebral fractures and recent past use or remote past use of opioids was observed. CONCLUSION: Among RA patients, the risk of nonvertebral fracture is increased in those treated with opioids. PMID- 26360964 TI - Lipid peroxidation and total glutathione after different intensities of resistance exercise in trained men. AB - AIM: Since studies on resistance exercise and oxidative stress markers show contradictory results, it is not clear whether different intensities of exercise are the determinant of changes in such markers. The objective of this study was to investigate the acute effects of different intensities of resistance exercise on lipid peroxidation and total glutathione in previously resistance trained men. METHODS: Eight male subjects with at least 2 years of resistance training experience performed two different resistance exercise protocols: low-intensity (LI), 60% of one repetition maximum (1RM) and high-intensity (HI), 85% of 1RM. Both protocols involved seven exercises and subjects performed one set of each exercise. Blood samples were obtained before and immediately after exercise for lipid peroxidation and total glutathione analysis. RESULTS: The results indicated a significant difference in total workload (load multiplied by repetitions performed) between the LI and HI protocols (P<0.05) and no differences on lipid peroxidation and total glutathione after both LI and HI protocols. CONCLUSION: This study suggests that resistance exercise protocols composed of a single set of seven exercises, regardless of the intensity or total workload do not induce to oxidative stress, suggesting that volume is the main variable to induce oxidative stress in previously resistance trained individuals. PMID- 26360965 TI - Anthropometric and somatotype characteristics of world class male roller skaters by discipline. AB - AIM: The aim of this study was twofold: 1) to describe the anthropometric profile and somatotype of the elite male roller skaters; and: 2) to assess if there are any differences in these items by roller skating discipline (figures, freestyle, pair and dance). METHODS: Eighty-eight male skater participants in the 51st Figure Roller Skating World Championship were selected for the study. The International Society for the Advancement of Kinanthropometry (ISAK) protocol was used to determine the anthropometric profile of the figure skaters. Additionally, Body Mass Index (BMI), sum of four and six skinfolds and somatotype were also analysed. RESULTS: No significant differences were found for the sum of four and six skinfolds among disciplines. Significant differences were found for flexed arm (P<=0.05), forearm (P<=0.05) and wrist girths (P<=0.001) between artistic roller figure and pair skaters. Significant differences were found in waist girth (P<=0.05), flexed arm, forearm and wrist girths (P<=0.001) between artistic roller freestyle and pairs skaters. No differences were found in lower limbs girths among disciplines. Significant differences were found in humerus (P<0.05) and bistyloid (P<0.05) breadth among disciplines. The general somatotype is endo mesomorphic for roller freestyle and figure skaters. In pair skaters the somatotype is ecto-mesomorphic, and for dance skaters it is balanced mesomorphic. PMID- 26360966 TI - The impact of rapid weight loss on the leptin, adiponectin levels, and insulinresistance among adult free style wrestlers. AB - AIM: Recent studies, shows the effective role of adipose tissue as an active endocrine organ. Leptin level increases in obese bodies while adiponectin as an antirisk factor reduction that contributes to decrease insulin resistance and anthropometric profiles. Hence, expected to the negative effects of weight loss on wrestlers' physiological function; leptin and adiponectin behaviors and insulin resistance in young wrestlers during their rapid weight loss program were examined. METHODS: Fifteen young (23+/-1 yr) freestyle wrestlers with (weight 67.6+/-0.8 kg, BMI 22.5+/-0.2 kg/m2) in two (60 and 66 kg) weight categories were selected randomly. Caloric intake and anthropometric characteristics measured by standard methods. The leptin and adiponectin hormones and insulin resistance index were measured by sandwich and HOMA-IR methods respectively. Wrestlers performed a week rapid weight loss Protocol (average of 4% of body weight loss) under the supervision of their coach. Eventually, selected factors were measured after 12 and 24 hours of recovery, again. RESULTS: The rapid weight loss (4%) program had a significantly reduced impact on anthropometric factors; leptin level, insulin resistance, and increased beta cell function, while the changes of adiponectin were not significant after weight loss. CONCLUSION: Findings of this study shows that dramatic decrease in anthropometric factors follow the weight loss program that having a significant decrease on leptin, L/A ratio and HOMA-IR, without significant changes in adiponectin levels. These changes may have harmful physiological effects on wrestlers' bodies but they can be useful to regulate of fatty acid, glucose metabolism, and insulin resistance. PMID- 26360967 TI - The mediating role of mental toughness in sport. AB - AIM: We conducted two studies that examined different models, which included mental toughness and psychological constructs that are thought to be related to this construct. METHODS: In Study 1, 531 athletes completed measures of mental toughness, resilience, and emotional intelligence. In Study 2, 522 athletes completed measures of mental toughness, sport motivation, and self-efficacy. RESULTS: There were positive paths between the constructs in the model, which were mediated by mental toughness in Study 1. Further, there was a positive path between mental toughness and self-efficacy, but negative paths with introjected regulation and amotivation in Study 2. CONCLUSION: This two study paper suggests that it might also be the presence of constructs such as resilience, emotional intelligence, motivation, and/or self-efficacy that enable mentally tough individuals to excel under stressful circumstances rather than just coping. PMID- 26360968 TI - Physical activity, but not fitness level, is associated with depression in Australian adults. AB - AIM: The objective of this study was to evaluate the fitness and physical activity levels of people referred to a nutrition and physical activity program for the management of mental health in general practice. METHODS: General practitioners referred 109 patients being treated for depression and/or anxiety to a lifestyle intervention program. All participants completed anthropometric measurements and questionnaires including the Depression, Anxiety and Stress Scale (DASS) and the Active Australia Survey. Aerobic fitness was measured with the YMCA step test and muscular fitness was measured with repeated chair stands and arm curls. Fitness scores were compared to population norms, and physical activity levels were compared to population norms and national recommendations. RESULTS: Eighty percent of participants were overweight or obese. A greater proportion of study participants (51%) than the general Australian population (38%) met the recommended 150 minutes per week spent in moderate physical activity. However, participants demonstrated lower than average levels of fitness and participated in low levels of vigorous physical activity. CONCLUSION: Levels of physical activity, but not fitness, were inversely correlated with DASS scores. Patients presenting with depression and/or anxiety should be screened for physical activity behaviours and encouraged to meet the National Physical Activity Guidelines. PMID- 26360969 TI - Riboflavin attenuates lipopolysaccharide-induced lung injury in rats. AB - Riboflavin (vitamin B2) is an easily absorbed micronutrient with a key role in maintaining health in humans and animals. It is the central component of the cofactors flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) and is therefore required by all flavoproteins. Riboflavin also works as an antioxidant by scavenging free radicals. The present study was designed to evaluate the effects of riboflavin against acute lungs injury induced by the administration of a single intranasal dose (20 MUg/rat) of lipopolysaccharides (LPS) in experimental rats. Administration of LPS resulted in marked increase in malondialdehyde (MDA) level (p < 0.01) and MPO activity (p < 0.001), whereas marked decrease in glutathione (GSH) content (p < 0.001), glutathione reductase (GR) (p < 0.001) and glutathione peroxidase (p < 0.01) activity. These changes were significantly (p < 0.001) improved by treatment with riboflavin in a dose dependent manner (30 and 100 mg/kg, respectively). Riboflavin (100 mg/kg, p.o.) showed similar protective effects as dexamethasone (1 mg/kg, p.o.). Administration of LPS showed marked cellular changes including interstitial edema, hemorrhage, infiltration of PMNs, etc., which were reversed by riboflavin administration. Histopathological examinations showed normal morphological structures of lungs tissue in the control group. These biochemical and histopathological examination were appended with iNOS and CAT gene expression. The iNOS mRNA expression was increased significantly (p < 0.001) and levels of CAT mRNA expression was decreased significantly (p < 0.001) in the animals exposed to LPS, while treatment with riboflavin significantly (p < 0.01) improved expression of both gene. In conclusion, the present study clearly demonstrated that riboflavin caused a protective effect against LPS-induced ALI. These results suggest that riboflavin may be used to protect against toxic effect of LPS in lungs. PMID- 26360970 TI - Unconditional cash transfers for assistance in humanitarian disasters: effect on use of health services and health outcomes in low- and middle-income countries. AB - BACKGROUND: Unconditional cash transfers (UCTs) are a common social protection intervention that increases income, a key social determinant of health, in disaster contexts in low- and middle-income countries (LMICs). OBJECTIVES: To assess the effects of UCTs in improving health services use, health outcomes, social determinants of health, health care expenditure, and local markets and infrastructure in LMICs. We also compared the relative effectiveness of UCTs delivered in-hand with in-kind transfers, conditional cash transfers, and UCTs paid through other mechanisms. SEARCH METHODS: We searched 17 academic databases, including the Cochrane Public Health Group Specialised Register, the Cochrane Database of Systematic Reviews (The Cochrane Library 2014, Issue 7), MEDLINE, and EMBASE between May and July 2014 for any records published up until 4 May 2014. We also searched grey literature databases, organisational websites, reference lists of included records, and academic journals, as well as seeking expert advice. SELECTION CRITERIA: We included randomised and quasi-randomised controlled trials (RCTs), as well as cohort, interrupted time series, and controlled before-and-after studies (CBAs) on UCTs in LMICs. Primary outcomes were the use of health services and health outcomes. DATA COLLECTION AND ANALYSIS: Two authors independently screened all potentially relevant records for inclusion criteria, extracted the data, and assessed the included studies' risk of bias. We requested missing information from the study authors. MAIN RESULTS: Three studies (one cluster-RCT and two CBAs) comprising a total of 13,885 participants (9640 children and 4245 adults) as well as 1200 households in two LMICs (Nicaragua and Niger) met the inclusion criteria. They examined five UCTs between USD 145 and USD 250 (or more, depending on household characteristics) that were provided by governmental, non-governmental or research organisations during experiments or pilot programmes in response to droughts. Two studies examined the effectiveness of UCTs, and one study examined the relative effectiveness of in-hand UCTs compared with in-kind transfers and UCTs paid via mobile phone. Due to the methodologic limitations of the retrieved records, which carried a high risk of bias and very serious indirectness, we considered the body of evidence to be of very low overall quality and thus very uncertain across all outcomes.Depending on the specific health services use and health outcomes examined, the included studies either reported no evidence that UCTs had impacted the outcome, or they reported that UCTs improved the outcome. No single outcome was reported by more than one study. There was a very small increase in the proportion of children who received vitamin or iron supplements (mean difference (MD) 0.10 standard deviations (SDs), 95% confidence interval (CI) 0.06 to 0.14) and on the child's home environment, as well as clinically meaningful, very large reductions in the chance of child death (hazard ratio (HR) 0.26, 95% CI 0.10 to 0.66) and the incidence of severe acute malnutrition (HR 0.44, 95% CI 0.24 to 0.80). There was also a moderate reduction in the number of days children spent sick in bed (MD - 0.36 SDs, 95% CI - 0.62 to - 0.10). There was no evidence for any effect on the proportion of children receiving deworming drugs, height for age among children, adults' level of depression, or the quality of parenting behaviour. No adverse effects were identified. The included comparisons did not examine several important outcomes, including food security and equity impacts.With regard to the relative effectiveness of UCTs compared with a food transfer providing a relatively high total caloric value, there was no evidence that a UCT had any effect on the chance of child death (HR 2.27, 95% CI 0.69 to 7.44) or severe acute malnutrition (HR 1.15, 95% CI 0.67 to 1.99). A UCT paid in hand led to a clinically meaningful, moderate increase in the household dietary diversity score, compared with the same UCT paid via mobile phone (difference-in differences estimator 0.43 scores, 95% CI 0.06 to 0.80), but there was no evidence for an effect on social determinants of health, health service expenditure, or local markets and infrastructure. AUTHORS' CONCLUSIONS: Additional high-quality evidence (especially RCTs of humanitarian disaster contexts other than droughts) is required to reach clear conclusions regarding the effectiveness and relative effectiveness of UCTs for improving health services use and health outcomes in humanitarian disasters in LMICs. PMID- 26360971 TI - From There and Back Again. AB - This article describes my journey from being a radical, person-centered therapist in the 1960s to the present. In the 1960s, my colleagues and I saw therapy as a person-to-person encounter. Over the years I lost that notion and became corrupted by the idea that therapy is a process of intervening to make things happen in clients. In the 1990s, I found my way back to the idea of therapy as a meeting of persons because of a research review that showed that it was clients' investment and creativity that were primarily responsible for making therapy work and because of my experiences with clients. In the meantime, the field had aged and political developments within it, such as the empirically supported treatments movement, also influenced how I came to view myself. I conclude by giving my current view of therapy as a process in which I am not intervening but engaging in a person-to-person meeting, within which I am free to offer techniques and ideas from many different approaches if appropriate. PMID- 26360973 TI - Risk of Stroke in Patients with Inflammatory Bowel Disease: A Systematic Review and Meta-analysis. AB - OBJECTIVE: Observational studies, to date, have provided inconsistent findings on whether inflammatory bowel disease (IBD) is associated with an increased risk of stroke. We therefore performed a meta-analysis to evaluate the association of IBD and its specific subtypes with risk of stroke. DESIGN: We searched electronic databases for studies through May 13, 2015 assessing risk of stroke in patients with IBD. Cohort and case-control studies that reported incident cases of stroke in patients with IBD and a non-IBD control population were eligible. We calculated pooled hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: A total of 8 articles (126,493 IBD patients and 4748 cases of stroke) were included in this meta-analysis. The presence of IBD revealed a trend toward a modest increase in the risk of stroke incidence (HR = 1.29; 95% CI, 1.16-1.43). After subgroup analysis, Crohn's disease showed an increased risk of stroke incidence (7 studies: HR = 1.32; 95% CI, 1.13-1.56), and a significant association was also identified in ulcerative colitis (6 studies: HR = 1.18; 95% CI, 1.06-1.31). In addition, this risk is higher in women (6 studies: HR = 1.49; 95% CI, 1.24-1.79) than in men (HR = 1.22; 95% CI, 1.12-1.32). In the overall analysis we found considerable heterogeneity. CONCLUSION: Our results show a positive association between IBD and the risk of stroke. PMID- 26360974 TI - Effect of Kinesiology Tape on Measurements of Balance in Subjects With Chronic Ankle Instability: A Randomized Controlled Trial. AB - OBJECTIVE: To examine the immediate and prolonged effects (7d) of Kinesiology Tape (KT) on balance in subjects with chronic ankle instability using computerized dynamic posturography (CDP). DESIGN: A 7-day follow-up, single-blind randomized controlled trial. SETTING: University community. PARTICIPANTS: Subjects (N=36) were screened for possible eligibility criteria, and 30 successfully completed the study protocol. Of these, 15 were randomly assigned to the experimental group (KT: 5 men, 10 women), and 15 were assigned to the control group (placebo tape: 10 men, 5 women). INTERVENTIONS: The experimental group was taped for a lateral ankle sprain with KT. In the control group, a placebo tape was used. Balance was assessed under the following 3 conditions: without taping, immediately after application, and after 7 days of use. MAIN OUTCOME MEASURES: The CDP device used in this study was the Smart Equitest version 8.2. CDP analysis was conducted using the Sensory Organization Test (SOT). As primaries outcome measures, the composite SOT score and composite SOT strategy were chosen. The partial score for SOT condition 2 and its strategy were considered as the secondary outcomes measures. RESULTS: Repeated-measures analysis of variance (ANOVA) demonstrated that there was not a significant interaction between group and time in the composite SOT score (F=.239; P=.73), SOT condition 2 (F=.333; P=.705), and SOT strategy 2 (F=.899; P=.43). Additionally, repeated-measures ANOVA showed a significant effect for time (composite SOT score: F=40.69; P<=.01; SOT condition 2: F=4.61; P=.014; SOT strategy 2: F=.899; P=.413; composite SOT strategy: F=15.14; P<=.01). Specifically, post hoc analysis showed that both groups obtained improvements in composite SOT scores immediately after tape application and 7 days of use. CONCLUSIONS: According to our results, the SOT scores of both the KT and control groups improved during follow-up. No differences between them were observed during the follow-up in most balance measurements. The observed changes may be related to a subjective increase in confidence after the tape application. PMID- 26360975 TI - Effectiveness of Exergaming Training in Reducing Risk and Incidence of Falls in Frail Older Adults With a History of Falls. AB - OBJECTIVE: To use Nintendo's Wii Fit balance board to determine the effectiveness of exergaming training in reducing risk and incidence of falls in older adults with a history of falls. DESIGN: Randomized controlled trial. SETTING: Nursing home for older adults. PARTICIPANTS: Adults aged 65 years and older (N=60). INTERVENTIONS: Participants who lived in a nursing home had 6 weeks of balance training with either Wii Fit equipment or conventional exercise. MAIN OUTCOME MEASURES: Physiological Profile Assessment scores and incidence of falls were observed with subsequent intention-to-treat statistical analyses. RESULTS: Physiological Profile Assessment scores and incidence of falls improved significantly in both groups after the intervention (all P<.01), but participants in the Wii Fit training group showed a significantly greater improvement in both outcome measures (P=.004 and P<.001, respectively). CONCLUSIONS: In institutionalized older adults with a history of falls, Wii Fit balance training was more effective than conventional balance training in reducing the risk and incidence of falls. PMID- 26360976 TI - Utility of Contrast-enhanced Ultrasonography with Perflubutane for Determining Histologic Grade in Hepatocellular Carcinoma. AB - The purpose of this study was to clarify the diagnostic value of contrast enhanced ultrasonography (CEUS) with perflubutane in determining the histologic grade in hepatocellular carcinoma (HCC). A total of 147 surgically resected HCCs were dichotomized as well differentiated HCC (wd-HCC) and moderately- or poorly differentiated HCC (mp-HCC). CEUS findings were evaluated during the arterial phase (vascularity, level and shape of enhancement), portal phase (presence or absence of washout) and post-vascular phase (echo intensity and shape). Receiver operating characteristic (ROC) curve analysis for the diagnosis of mp-HCC yielded area under the ROC curve (Az) values for arterial phase vascularity and portal phase washout of 0.910 and 0.807, respectively. The Az value for the combination of vascularity and washout for the diagnosis of mp-HCC was 0.956 (95% confidence interval, 0.910-0.979), corresponding to high diagnostic value. In conclusion, CEUS can provide high-quality imaging assessment for determining the histologic grade of HCCs. PMID- 26360972 TI - Multicenter Study of Intravenous Recombinant Tissue Plasminogen Activator Infusion around Hiroshima, Japan: The Hiroshima Acute Stroke Retrospective and Prospective Registry Study. AB - OBJECTIVE: Approximately 10 years have passed since intravenous (IV) recombinant tissue plasminogen activator therapy was approved in Japan. The aim of this retrospective study was to identify the effectiveness and safety of IV alteplase therapy with the Japanese original dose around Hiroshima via consideration of the patients' backgrounds, examination findings, and outcomes. METHODS: All consecutive patients with ischemic stroke who received IV alteplase therapy between October 2005 and October 2010 were registered. RESULTS: Four hundred twenty-nine patients with ischemic stroke (172 female [40.1%], mean age 73.7 +/- 11.8 years) were registered. The proportion of patients over 75 years old was 51.5% (221 patients). The median National Institutes of Health Stroke Scale (NIHSS) scores at admission were 13 (interquartile range, 9-19), and the NIHSS scores 24 hours after alteplase infusion were 8 (interquartile range, 3-15). The proportion of intracerebral hemorrhage within the initial 36 hours was 20.2% (86 patients). After the multivariate regression analysis, a history of hypertension (odds ratio = 4.14; 95% confidence interval, 1.32-14.79; P = .01) and no recanalization (odds ratio = 10.10; 95% confidence interval, 3.03-39.33; P < .0001) were independently associated with a modified Rankin Scale (mRS) score of 2 or higher at 3 months. Patients over 75 years old were not significantly associated with an intracerebral hemorrhage within the initial 36 hours and an mRS score of 2 or higher at 3 months. CONCLUSIONS: The results of our study demonstrated that IV alteplase therapy with the Japanese original dose was effective and exhibited a safety profile similar to other studies. Moreover, we should not hesitate to IV alteplase therapy simply because of advanced age. PMID- 26360977 TI - Estimation of Large-Scale Organ Motion in B-Mode Ultrasound Image Sequences: A Survey. AB - Reviewed here are methods developed for following (i.e., tracking) structures in medical B-mode ultrasound time sequences during large-scale motion. The resulting motion estimation problem and its key components are defined. The main tracking approaches are described, and their strengths and weaknesses are discussed. Existing motion estimation methods, tested on multiple in vivo sequences, are categorized with respect to their clinical applications, namely, cardiac, respiratory and muscular motion. A large number of works in this field had to be discarded as thorough validation of the results was missing. The remaining relevant works identified indicate the possibility of reaching an average tracking accuracy up to 1-2 mm. Real-time performance can be achieved using several methods. Yet only very few of these have progressed to clinical practice. The latest trends include incorporation of complementary and prior information. Advances are expected from common evaluation databases and 4-D ultrasound scanning technologies. PMID- 26360978 TI - The two dimensions of the body representation in women suffering from Anorexia Nervosa. AB - A core symptom of Anorexia Nervosa (AN) is a severe alteration of body representations. Evidence from somatoperception studies point to a generic disturbances of somatosensory components of body representations. Here we have investigated whether AN patients (N=18) and controls differed in the perception of tactile stimuli differently oriented along the body axes. We tested the hypothesis that patients perceive and represent their body selectively larger in only one dimension. To this aim we used elementary tactile measures for tactile acuity (Von Frey's test and two-point discrimination thresholds - 2PD) and tactile discrimination measures. The rationale is based on the assumption that AN patients have a wider body representation, and that tactile body representation tasks (Tactile Distance task) oriented across the bodies (horizontally) are influenced by distorted body representations compared with tactile stimuli oriented along the bodies (vertically) which should not be influenced by body representations. Results showed that patients judged horizontal tactile stimuli significantly wider than the same stimuli oriented vertically.These results suggest that human brain perceives things differently based on body representations and that the beliefs concerning body size influence the specific somatosensory process of tactile experience. PMID- 26360979 TI - Fasudil Is an Effective Graft Vasodilator for Gastroepiploic Artery in Coronary Artery Bypass Grafting. AB - OBJECTIVE: The gastroepiploic artery (GEA) has been used as an alternative arterial in situ graft for coronary artery bypass grafting (CABG). However, because of the large individual differences and the spastic nature of the GEA, caution has to be exercised during harvesting. We evaluated the usefulness of fasudil, a Rho kinase inhibitor, as a vasodilator for right GEA (RGEA) graft after harvesting, compared with the conventional agents papaverine and verapamil nitroglycerin. METHODS: Between June 2009 and January 2013, 30 patients with ischemic heart disease who underwent isolated CABG using RGEA graft were randomly assigned to fasudil (n = 10), papaverine (n = 10), or verapamil-nitroglycerin (n = 10) group. Fasudil (2.67 mmol/L), papaverine (1.0 mmol/L) mixed with heparinized blood, or verapamil-nitroglycerin (30 MUmol/L each) was injected intraluminally into the RGEA graft after harvesting. Right GEA graft free flow (GFF), hemodynamic changes, and histopathology of RGEA were evaluated. RESULTS: Intraluminal injection of fasudil increased GFF significantly (P < 0.001) and markedly from 41.5 +/- 31.5 mL/min at baseline to 149.3 +/- 46.7 mL/min after injection. Papaverine increased GFF (P < 0.001) from 40.0 +/- 35.8 to 64.9 +/- 33.7 mL/min, and verapamil-nitroglycerin also increased GFF (P < 0.001) from 38.8 +/- 32.1 to 79.0 +/- 35.2 mL/min. The GFF was significantly higher (P = 0.001) in the fasudil group than in the other two groups. Histopathologically, fasudil treatment markedly increased the diameter of RGEA graft, while maintaining integrity of the multiple elastic lamellae. Blood pressure did not change significantly after drug injection in all groups. CONCLUSIONS: Fasudil is more potent than papaverine or verapamil-nitroglycerin in increasing GFF of RGEA graft for CABG. PMID- 26360981 TI - The right place at the right time. PMID- 26360980 TI - Parannular Elliptical Posterior Resection: A Low-Impact Reparative Technique for Mitral Valve Prolapse. AB - OBJECTIVE: Although effective, Carpentier technique for mitral regurgitation presents two "Achille's heel": the resection of the whole prolapsing section of posterior mitral leaflet (PML) including chordae tendinae and the annular distortion due to plication. An alternative technique of limited PML resection, which preserves mitral anatomy decreasing the impact on valve function, and 9 year outcome are presented. METHODS: Since April 2005 till March 2014, of 205 patients affected by mitral prolapse scheduled for repair (mitral valve repair), 54 patients have been included in the study. The rationale of the new technique was to limit PML resection to achieve a fair reduction of the prolapsing scallop(s) height, to avoid leaflet and annular distortion, and to spare the coaptation surface and other substantial structures. According to the observation that the posterior smooth zone of PML is quite free from chordal insertions, an elliptical slice of tissue was resected from this area. Annuloplasty and neochordal insertion when indicated completed the procedure. RESULTS: Up to 9 years of follow-up was 98% complete. One in-hospital death, two late noncardiac deaths, one redo operation due to endocarditis were reported. On late follow-up, 92% patients were on New York Heart Association class I. Late echocardiography showed stability of repair (regurgitation grade of <=1 in 92% of patients). Nearly two third of valves preserved good PML mobility. CONCLUSIONS: The parannular elliptical posterior leaflet resection, providing excellent stable midterm results, seems to be a safe alternative method for repair of PML prolapse. It avoids distortion and weakening of annulus and leaflet, and it allows restoring a proper coaptation surface and maintains a satisfactory PML motion. PMID- 26360982 TI - Unrecognised and untreated depression in cancer care. PMID- 26360983 TI - Treatment of bipolar disorder: not another meta-analysis. PMID- 26360984 TI - Cocaine, progesterone, and post-partum women. PMID- 26360985 TI - Improving outcomes in social anxiety disorder. PMID- 26360986 TI - Mental health technologies and the needs of cultural groups. PMID- 26360987 TI - Teaching global mental health at home and abroad. PMID- 26360988 TI - Chromosomal microarray analysis-a routine clinical genetic test for patients with schizophrenia. PMID- 26360990 TI - PTSD diagnoses can avoid avoidance as an absolute criterion. PMID- 26360989 TI - Ways forward for treating depressed patients with cancer. PMID- 26360991 TI - Integrating alienists. PMID- 26360994 TI - Social media: toxified by rage. PMID- 26360993 TI - Gun violence and mental illness. PMID- 26360995 TI - Kimberly Yonkers. PMID- 26360996 TI - Art as a therapeutic intervention in schizophrenia. PMID- 26360997 TI - A quest for understanding. PMID- 26360998 TI - Prevalence, associations, and adequacy of treatment of major depression in patients with cancer: a cross-sectional analysis of routinely collected clinical data. AB - BACKGROUND: Major depression is an important complication of cancer. However, reliable data are lacking for the prevalence of depression in patients with cancer in different primary sites, the association of depression with demographic and clinical variables within cancer groupings, and the proportion of depressed patients with cancer receiving potentially effective treatment for depression. We investigated these questions with data from a large representative clinical sample. METHODS: We analysed data from patients with breast, lung, colorectal, genitourinary, or gynaecological cancer who had participated in routine screening for depression in cancer clinics in Scotland, UK between May 12, 2008, and Aug 24, 2011. Depression screening was done in two stages (first, Hospital Anxiety and Depression Scale; then, major depression section of the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition). Data for depression status were linked with demographic and clinical data obtained from the Scottish National Cancer Registry. FINDINGS: We analysed data for 21 151 patients. The prevalence of major depression was highest in patients with lung cancer (13.1%, 95% CI 11.9-14.2%), followed by gynaecological cancer (10.9%, 9.8-12.1), breast cancer (9.3%, 8.7-10.0), colorectal cancer (7.0%, 6.1-8.0), and genitourinary cancer (5.6%, 4.5-6.7). Within these cancer groupings, a diagnosis of major depression was more likely in patients who were younger, had worse social deprivation scores, and, for lung cancer and colorectal cancer, female patients. 1130 (73%) of 1538 patients with depression and complete patient-reported treatment data were not receiving potentially effective treatment. INTERPRETATION: Major depression is common in patients attending cancer clinics and most goes untreated. A pressing need exists to improve the management of major depression for patients attending specialist cancer services. FUNDING: Cancer Research UK and Chief Scientist Office of the Scottish Government. PMID- 26360999 TI - Comparative efficacy and tolerability of pharmacological treatments in the maintenance treatment of bipolar disorder: a systematic review and network meta analysis. AB - BACKGROUND: Lithium is the established standard in the long-term treatment of bipolar disorder, but several new drugs have been assessed for this indication. We did a network meta-analysis to investigate the comparative efficacy and tolerability of available pharmacological treatment strategies for bipolar disorder. METHODS: We systematically searched Embase, Medline, PreMedline, PsycINFO, and the Cochrane Central Register of Controlled Trials for randomised controlled trials published before June 28, 2013, that compared active treatments for bipolar disorder (or placebo), either as monotherapy or as add-on treatment, for at least 12 weeks. The primary outcomes were the number of participants with recurrence of any mood episode, and the number of participants who discontinued the trial because of adverse events. We assessed efficacy and tolerability of bipolar treatments using a random-effects network meta-analysis within a Bayesian framework. FINDINGS: We screened 114 potentially eligible studies and identified 33 randomised controlled trials, published between 1970 and 2012, that examined 17 treatments for bipolar disorder (or placebo) in 6846 participants. Participants assigned to all assessed treatments had a significantly lower risk of any mood relapse or recurrence compared with placebo, except for those assigned to aripiprazole (risk ratio [RR] 0.62, 95% credible interval [CrI] 0.38 1.03), carbamazepine (RR 0.68, 0.44-1.06), imipramine (RR 0.95, 0.66-1.36), and paliperidone (RR 0.84, 0.56-1.24). Lamotrigine and placebo were significantly better tolerated than carbamazepine (lamotrigine, RR 5.24, 1.07-26.32; placebo, RR 3.60, 1.04-12.94), lithium (RR 3.76, 1.13-12.66; RR 2.58, 1.33-5.39), or lithium plus valproate (RR 5.95, 1.02-33.33; RR 4.09, 1.01-16.96). INTERPRETATION: Although most of the drugs analysed were more efficacious than placebo and generally well tolerated, differences in the quality of evidence and the side-effect profiles should be taken into consideration by clinicians and patients. In view of the efficacy in prevention of both manic episode and depressive episode relapse or recurrence and the better quality of the supporting evidence, lithium should remain the first-line treatment when prescribing a relapse-prevention drug in patients with bipolar disorder, notwithstanding its tolerability profile. FUNDING: None. PMID- 26361000 TI - Psychological and pharmacological interventions for social anxiety disorder in adults: a systematic review and network meta-analysis. AB - BACKGROUND: Social anxiety disorder-a chronic and naturally unremitting disease that causes substantial impairment-can be treated with pharmacological, psychological, and self-help interventions. We aimed to compare these interventions and to identify which are most effective for the acute treatment of social anxiety disorder in adults. METHODS: We did a systematic review and network meta-analysis of interventions for adults with social anxiety disorder, identified from published and unpublished sources between 1988 and Sept 13, 2013. We analysed interventions by class and individually. Outcomes were validated measures of social anxiety, reported as standardised mean differences (SMDs) compared with a waitlist reference. This study is registered with PROSPERO, number CRD42012003146. FINDINGS: We included 101 trials (13 164 participants) of 41 interventions or control conditions (17 classes) in the analyses. Classes of pharmacological interventions that had greater effects on outcomes compared with waitlist were monoamine oxidase inhibitors (SMD -1.01, 95% credible interval [CrI] -1.56 to -0.45), benzodiazepines (-0.96, -1.56 to -0.36), selective serotonin-reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors (SSRIs and SNRIs; -0.91, -1.23 to -0.60), and anticonvulsants (-0.81, -1.36 to 0.28). Compared with waitlist, efficacious classes of psychological interventions were individual cognitive-behavioural therapy (CBT; SMD -1.19, 95% CrI -1.56 to 0.81), group CBT (-0.92, -1.33 to -0.51), exposure and social skills (-0.86, 1.42 to -0.29), self-help with support (-0.86, -1.36 to -0.36), self-help without support (-0.75, -1.25 to -0.26), and psychodynamic psychotherapy (-0.62, -0.93 to -0.31). Individual CBT compared with psychological placebo (SMD -0.56, 95% CrI 1.00 to -0.11), and SSRIs and SNRIs compared with pill placebo (-0.44, -0.67 to 0.22) were the only classes of interventions that had greater effects on outcomes than appropriate placebo. Individual CBT also had a greater effect than psychodynamic psychotherapy (SMD -0.56, 95% CrI -1.03 to -0.11) and interpersonal psychotherapy, mindfulness, and supportive therapy (-0.82, -1.41 to -0.24). INTERPRETATION: Individual CBT (which other studies have shown to have a lower risk of side-effects than pharmacotherapy) is associated with large effect sizes. Thus, it should be regarded as the best intervention for the initial treatment of social anxiety disorder. For individuals who decline psychological intervention, SSRIs show the most consistent evidence of benefit. FUNDING: National Institute for Health and Care Excellence. PMID- 26361001 TI - Mental health interventions in schools in low-income and middle-income countries. AB - Increasing enrolment rates could place schools in a crucial position to support mental health in low-income and middle-income countries. In this Review, we provide evidence for mental health interventions in schools in accordance with a public mental health approach spanning promotion, prevention, and treatment. We identified a systematic review for mental health promotion, and identified further prevention and treatment studies. Present evidence supports schools as places for promotion of positive aspects of mental health using a whole-school approach. Knowledge of effectiveness of prevention and treatment interventions is more widely available for conflict-affected children and adolescents. More evidence is needed to identify the many elements likely to be associated with effective prevention and treatment for children exposed to a range of adversity and types of mental disorders. Dissemination and implementation science is crucial to establish how proven effective interventions could be scaled up and implemented in schools. PMID- 26361003 TI - Broken wires, healing minds. PMID- 26361002 TI - Computational psychiatry: a Rosetta Stone linking the brain to mental illness. PMID- 26361004 TI - Electrospun Scaffolds for Osteoblast Cells: Peptide-Induced Concentration Dependent Improvements of Polycaprolactone. AB - The design of hybrid poly-epsilon-caprolactone (PCL)-self-assembling peptides (SAPs) matrices represents a simple method for the surface functionalization of synthetic scaffolds, which is essential for cell compatibility. This study investigates the influence of increasing concentrations (2.5%, 5%, 10% and 15% w/w SAP compared to PCL) of three different SAPs on the physico chemical/mechanical and biological properties of PCL fibers. We demonstrated that physico-chemical surface characteristics were slightly improved at increasing SAP concentrations: the fiber diameter increased; surface wettability increased with the first SAP addition (2.5%) and slightly less for the following ones; SAP surface density increased but no change in the conformation was registered. These results could allow engineering matrices with structural characteristics and desired wettability according to the needs and the cell system used. The biological and mechanical characteristics of these scaffolds showed a particular trend at increasing SAP concentrations suggesting a prevailing correlation between cell behavior and mechanical features of the matrices. As compared with bare PCL, SAP enrichment increased the number of metabolic active h-osteoblast cells, fostered the expression of specific osteoblast-related mRNA transcripts, and guided calcium deposition, revealing the potential application of PCL-SAP scaffolds for the maintenance of osteoblast phenotype. PMID- 26361005 TI - ENT mucormycosis. Report of 4 cases. AB - OBJECTIVES: Mucormycosis is an opportunist infection usually affecting immunocompromised patients. It is rare and often fatal. The pathogen is filamentous fungus of the mucorales order. Studies discuss the clinical, diagnostic and therapeutic aspects of ENT mucormycosis, insisting on early clinical diagnosis, laboratory data not being contributive within satisfactory time limits. MATERIAL AND METHODS: A retrospective study included 4 patients with ENT mucormycosis diagnosed over a 13-year period, from January 2000 to December 2012. RESULTS: The study included 2 male and 2 female patients, aged from 3 to 77 years. Two patients were diabetic. There were 2 cases of sinonasal mucormycosis and 2 of otologic involvement. Diagnosis was founded on anatomopathologic and mycologic examination. A fatal issue occurred in 1 case with otocerebral involvement. CONCLUSIONS: Otorhinolaryngologic mucormycosis is a rare fungal infection, which needs to be borne in mind. Rhinocerebral lesions are the most common clinical manifestations. Involvement of the ear is very rare. Diagnosis is often difficult, but should be as early as possible. Treatment, initiated urgently, associates antifungal treatment, surgical resection and control of risk factors. The prognosis remains in all cases severe. PMID- 26361006 TI - Unicentric Castleman's disease in the posterior cervical space mimicking a schwannoma. AB - INTRODUCTION: Castleman's disease (CD) is a benign and rare lymphoid tissue disease of undetermined origin. It affects the neck infrequently; therefore its preoperative diagnosis is difficult and can be confused with other hypervascular lesions. CASE REPORT: We present a case of unicentric hyaline-vascular CD in the posterior cervical space (PCS) evaluated by MRI and initially presumed to be a cervical schwannoma. DISCUSSION: As shown with our case, unicentric CD should be included in the differential diagnosis for masses in the PCS, especially when a hypervascular lesion like a schwannoma is suspected. The finding of central low intensity areas in a fissured and radial pattern in T2 sequences can help to consider CD when dealing with PCS masses as shown by previous cases and our reported experience. PMID- 26361007 TI - The Self beyond Somatic Symptoms: A Narrative Approach to Self-Experience in Adolescent Chronic Fatigue Syndrome. AB - BACKGROUND: The self and self-experience are often assumed to play an important role in adolescent patients presenting with severe somatic symptoms and bodily distress. Nonetheless, most empirical work on this subject is confined to studies of personality and patients' experience of negative emotionality. This study aims to move beyond mere descriptions of symptoms, traits and distress, and consequently adopts a narrative approach to self-experience in adolescent chronic fatigue syndrome (CFS). SAMPLING AND METHODS: The self-confrontation method (SCM) is a well-validated instrument to systematically analyze narrative self experience. The SCM was used to study 42 adolescents with CFS, compared to 36 adolescents with juvenile idiopathic arthritis (JIA) and 25 matched healthy controls. The Child Health Questionnaire (CHQ-CF87) was used to assess mental health, self-esteem, and physical and psychosocial functioning. RESULTS: Both patient groups reported significantly less positive self-experience of autonomy and success compared to healthy controls. Furthermore, patients with CFS described significantly more negative self-experience of powerlessness, isolation and unfulfilled longing. In the CHQ-CF87, both patient groups scored significantly lower on physical functioning than controls. Adolescents with CFS also scored significantly lower on mental health and self-esteem. CONCLUSIONS: Adolescent CFS entails a serious threat to the self, which might be inherent to the condition. Not only are patients more impaired in mental health, self-esteem, and physical and psychosocial functioning than patients with JIA, they also suffer from a distinct combination of high negative and low positive self experience. These findings stress the need for strategies that empower patients towards a 'management of the self'. PMID- 26361008 TI - Fast Second Degree Total Variation Method for Image Compressive Sensing. AB - This paper presents a computationally efficient algorithm for image compressive sensing reconstruction using a second degree total variation (HDTV2) regularization. Firstly, a preferably equivalent formulation of the HDTV2 functional is derived, which can be formulated as a weighted L1-L2 mixed norm of second degree image derivatives under the spectral decomposition framework. Secondly, using the equivalent formulation of HDTV2, we introduce an efficient forward-backward splitting (FBS) scheme to solve the HDTV2-based image reconstruction model. Furthermore, from the averaged non-expansive operator point of view, we make a detailed analysis on the convergence of the proposed FBS algorithm. Experiments on medical images demonstrate that the proposed method outperforms several fast algorithms of the TV and HDTV2 reconstruction models in terms of peak signal to noise ratio (PSNR), structural similarity index (SSIM) and convergence speed. PMID- 26361009 TI - Validation and User Evaluation of a Sensor-Based Method for Detecting Mobility Related Activities in Older Adults. AB - Regular physical activity is essential for older adults to stay healthy and independent. However, daily physical activity is generally low among older adults and mainly consists of activities such as standing and shuffling around indoors. Accurate measurement of this low-energy expenditure daily physical activity is crucial for stimulation of activity. The objective of this study was to assess the validity of a necklace-worn sensor-based method for detecting time-on-legs and daily life mobility related postures in older adults. In addition user opinion about the practical use of the sensor was evaluated. Twenty frail and non frail older adults performed a standardized and free movement protocol in their own home. Results of the sensor-based method were compared to video observation. Sensitivity, specificity and overall agreement of sensor outcomes compared to video observation were calculated. Mobility was assessed based on time-on-legs. Further assessment included the categories standing, sitting, walking and lying. Time-on-legs based sensitivity, specificity and percentage agreement were good to excellent and comparable to laboratory outcomes in other studies. Category-based sensitivity, specificity and overall agreement were moderate to excellent. The necklace-worn sensor is considered an acceptable valid instrument for assessing home-based physical activity based upon time-on-legs in frail and non-frail older adults, but category-based assessment of gait and postures could be further developed. PMID- 26361010 TI - A severe case of co-infection with Enterovirus 71 and vaccine-derived Poliovirus type II. AB - Enterovirus 71 (EV71) is often identified as the primary pathogen that directly leads to severe cases of HFMD, whereas the association between other enteroviruses and EV71 infection remains largely unclear. Here we report a rare case of a 5-year-old boy co-infected with EV71 and vaccine-derived Poliovirus (VDPV) type II, which were identified based on PCR and sequence analysis results and clinical symptoms and were characterized on CT. We determined that the EV71 strain belongs to the C4 subtype, and the VDPV II strain was closely genetically related to the reference Sabin type II strain. This report may improved our understanding of the clinical significance of the associations between clinical signs and the infectious properties of the involved pathogens. PMID- 26361011 TI - iTRAQ-based comparative proteomic analysis of Vero cells infected with virulent and CV777 vaccine strain-like strains of porcine epidemic diarrhea virus. AB - The re-emerging porcine epidemic diarrhea virus (PEDV) variant related diarrhea has been documented in China since late 2010 and now with global distribution. Currently, a virulent PEDV CH/YNKM-8/2013 and a CV777 vaccine strain-like AH-M have been successfully isolated from the clinical samples. To dissect out the underlying pathogenic mechanism of virulent PEDV and clarify the differences between virulent and CV777 vaccine strain-like PEDV infections, we performed an iTRAQ-based comparative quantitative proteomic study of Vero cells infected with both PEDV strains. A total of 661 and 474 differentially expressed proteins were identified upon virulent and CV777 vaccine strain-like isolates infection, respectively. Ingenuity Pathway Analysis was employed to investigate the canonical pathways and functional networks involved in both PEDV infections. Comprehensive studies have revealed that the PEDV virulent strain suppressed protein synthesis of Vero cells through down-regulating mTOR as well as its downstream targets 4EBP1 and p70S6K activities, which were validated by immunoblotting. In addition, the virulent strain could activate NF-kappaB pathway more intensively than the CV777 vaccine strain-like isolate, and elicit stronger inflammatory cascades as well. These data might provide new insights for elucidating the specific pathogenesis of PEDV infection, and pave the way for the development of effective therapeutic strategies. BIOLOGICAL SIGNIFICANCE: Porcine epidemic diarrhea is now worldwide distributed and causing huge economic losses to swine industry. The immunomodulation and pathogenesis between PEDV and host, as well as the difference between virulent and attenuated strains of PEDV infections are still largely unknown. In this study, we presented for the first application of proteomic analysis to compare whole cellular protein alterations induced by virulent and CV777 vaccine strain-like PEDV infections, which might contribute to understand the pathogenesis of PEDV and anti-viral strategy development. PMID- 26361012 TI - Evolutionary comparisons predict that dimerization of human cytochrome P450 aromatase increases its enzymatic activity and efficiency. AB - Estrogen is an essential vertebrate hormone synthesized from androgens involving multiple hydroxylations, catalyzed by cytochrome P450 aromatase (P450arom or CYP19) enzymes. Despite their importance, very few comparative studies have been conducted on vertebrate and/or mammalian P450arom enzymes, either structurally or functionally. Here we directly compared the human (h-) and porcine gonadal (p(g) ) P450arom, as p(g)-P450arom has very low catalytic efficiency, with a ten-fold higher affinity (Km) for a substrate (androstenedione) and ten-fold reduction in turnover (Vmax). We recombinantly expressed these proteins and compared their interactions on a membrane using a quartz crystal microbalance (QCM) and also with the electron donor protein cytochrome P450 oxidoreductase (CPR). Changes in frequency and dissipation in the QCM supported the h-P450arom forming a homodimer that agreed with the FRET data, but not p(g)-P450arom. Analysis of the X-ray crystal structure of the h-P450arom suggested a likely site of homo-dimerization and found that certain key interacting residues were not conserved in pg P450arom. Molecular dynamics simulations provide support for the importance of these residues in homo-dimerization. Here we propose that the lower affinity and higher activity with reduced release of intermediate metabolites by the h P450arom is as a consequence of its ability to form homodimers. The functional implications of dimerization provide an important mechanistic step in the requirement for efficient aromatization. PMID- 26361013 TI - Analysis of SOST expression using large minigenes reveals the MEF2C binding site in the evolutionarily conserved region (ECR5) enhancer mediates forskolin, but not 1,25-dihydroxyvitamin D3 or TGFbeta1 responsiveness. AB - Transcribed from the SOST gene, sclerostin is an osteocyte-derived negative regulator of bone formation that inhibits osteoblastogenesis via antagonism of the Wnt pathway. Sclerostin is a promising therapeutic target for low bone mass diseases and neutralizing antibody therapies that target sclerostin are in development. Diverse stimuli regulate SOST including the vitamin D hormone, forskolin (Fsk), bone morphogenic protein 2 (BMP-2), oncostatin M (OSM), dexamethasone (Dex), and transforming growth factor (TGFbeta1). To explore the mechanisms by which these compounds regulate SOST expression, we examined their ability to regulate a SOST reporter minigene containing the entire SOST locus including the downstream regionor mutant minigenes containing a deletion of the 1kb to -2kb promoter proximal region (-1kb), ECR2, ECR5, or two point mutations in the MEF2 binding site of ECR5 (ECR5/MEF2). Previous reports suggest that both the PTH and TGFbeta1 effects on SOST are mediated through ECR5 and that the action of PTH is mediated specifically via the MEF2 binding site at ECR5. Consistent with these reports, the suppressive effects of Fsk were abrogated following both ECR5 deletion and ECR5/MEF2 mutation. In contrast, we found that TGFbeta1 negatively regulated SOST and that neither ECR5 nor ECR5/MEF2 was involved. Surprisingly, none of these four deletions/mutations abrogated the suppressive effects of the vitamin D hormone, OSM, Dex, or TGFbeta1, or the positive effects of BMP-2. These data suggest that we need to move beyond ECR5 to understand SOST regulation. PMID- 26361014 TI - Long-term vitamin D deficiency in older adult C57BL/6 mice does not affect bone structure, remodeling and mineralization. AB - Animal models show that vitamin D deficiency may have severe consequences for skeletal health. However, most studies have been performed in young rodents for a relatively short period, while in older adult rodents the effects of long-term vitamin D deficiency on skeletal health have not been extensively studied. Therefore, the first aim of this study was to determine the effects of long-term vitamin D deficiency on bone structure, remodeling and mineralization in bones from older adult mice. The second aim was to determine the effects of long-term vitamin D deficiency on mRNA levels of genes involved in vitamin D metabolism in bones from older adult mice. Ten months old male C57BL/6 mice were fed a diet containing 0.5% calcium, 0.2% phosphate and 0 (n=8) or 1 (n=9) IU vitamin D3/gram for 14 months. At an age of 24 months, mice were sacrificed for histomorphometric and micro-computed tomography (micro-CT) analysis of humeri as well as analysis of CYP27B1, CYP24 and VDR mRNA levels in tibiae and kidneys using RT-qPCR. Plasma samples, obtained at 17 and 24 months of age, were used for measurements of 25 hydroxyvitamin D (25(OH)D) (all samples), phosphate and parathyroid hormone (PTH) (terminal samples) concentrations. At the age of 17 and 24 months, mean plasma 25(OH)D concentrations were below the detection limit (<4nmol/L) in mice receiving vitamin D deficient diets. Plasma phosphate and PTH concentrations did not differ between both groups. Micro-CT and histomorphometric analysis of bone mineral density, structure and remodeling did not reveal differences between control and vitamin D deficient mice. Long-term vitamin D deficiency did also not affect CYP27B1 mRNA levels in tibiae, while CYP24 mRNA levels in tibiae were below the detection threshold in both groups. VDR mRNA levels in tibiae from vitamin D deficient mice were 0.7 fold lower than those in control mice. In conclusion, long-term vitamin D deficiency in older adult C57BL/6 mice, accompanied by normal plasma PTH and phosphate concentrations, does not affect bone structure, remodeling and mineralization. In bone, expression levels of CYP27B1 are also not affected by long-term vitamin D deficiency in older adult C57BL/6 mice. Our results suggest that mice at old age have a low or absent response to vitamin D deficiency probably due to factors such as a decreased bone formation rate or a reduced response of bone cells to 25(OH)D and 1,25(OH)2D. Older adult mice may therefore be less useful for the study of the effects of vitamin D deficiency on bone health in older people. PMID- 26361015 TI - The effect of glucuronidation on isoflavone induced estrogen receptor (ER)alpha and ERbeta mediated coregulator interactions. AB - Non-prenylated isoflavone aglycones are known to have phyto-estrogenic properties and act as agonistic ligands on ERalpha and ERbeta due to their structural resemblance to 17beta-estradiol (E2). Genistein and daidzein are the two main dietary isoflavones; upon uptake they are extensively metabolized and exist nearly exclusively as their conjugated forms in biological fluids. Little is known about the effect of conjugation on the intrinsic estrogenic activities of these isoflavones. To characterize and compare the intrinsic estrogenic activities of genistein and daidzein, and their respective 7-O-glucuronide metabolites a cell-free assay system was employed that determines the ligand induced changes in ERalpha- and ERbeta-ligand binding domain (LBD) interactions with 154 different binding motifs derived from 66 different nuclear receptor coregulators. The glucuronides were 8 to 4400 times less potent than their respective aglycones to modulate ERalpha-LBD and ERbeta-LBD-coregulator interactions. Glucuronidation changed the preferential activation of genistein from ERbeta-LBD to ERalpha-LBD and further increased the slightly preferential activation of daidzein for ERalpha-LBD. The tested isoflavone compounds were less potent than E2 (around 5 to 1580 times for the aglycones) but modulated the LBD coregulator interactions in a manner similar to E2. Our results show that genistein and daidzein remain agonistic ligands of ERalpha-LBD and ERbeta-LBD in their conjugated form with a higher relative preference for ERalpha-LBD than the corresponding aglycones. This shift in receptor preference is of special interest as the preferential activation of ERbeta is considered one of the possible modes of action underlying the supposed beneficial instead of adverse health effects of isoflavones. PMID- 26361016 TI - Spatiotemporal Features of the Three-Dimensional Architectural Landscape in Qingdao, China. AB - The evolution and development of the three-dimensional (3D) architectural landscape is the basis of proper urban planning, eco-environment construction and the improvement of environmental quality. This paper presents the spatiotemporal characteristics of the 3D architectural landscape of the Shinan and Shibei districts in Qingdao, China, based on buildings' 3D information extracted from Quickbird images from 2003 to 2012, supported by Barista, landscape metrics and GIS. The results demonstrated that: (1) Shinan and Shibei districts expanded vertically and urban land use intensity increased noticeably from year to year. (2) Significant differences in the 3D architectural landscape existed among the western, central and eastern regions, and among the 26 sub-districts over the study period. The differentiation was consistent with the diverse development history, function and planning of the two districts. Finally, we found that population correlates positively with the variation in the 3D architectural landscape. This research provides an important reference for related studies, urban planning and eco-city construction. PMID- 26361017 TI - [Effect of educational level on the prognosis of acute myocardial infarction]. AB - BACKGROUND: Socioeconomic status is associated with cardiovascular mortality. AIM: To evaluate the effect of educational level, on the prognosis of patients with acute myocardial infarction in Chile. MATERIAL AND METHODS: Cohort study of 3,636 patients aged 63.1 +/- 13.2 years, 27% women, hospitalized in 16 centers participating in the Chilean Myocardial Infarction Registry (GEMI) between 2009 and 2012. Vital status was obtained from the National Mortality Database. Patients were divided, according to educational level, in four groups, namely none (no formal education), basic (< 8 years), secondary (8-12 years) and tertiary (> 12 years). Crude and adjusted (age, sex, cardiovascular risk factors and treatments) hazard ratios (HR) were estimated using Cox regression models. RESULTS: The distribution by educational level was 3.2% none, 31.8% basic, 43.0% secondary and 22.0% tertiary. During a median follow-up period of 22 months (interquartile range 11-37 years), 631 patients died (17.3%), of whom 198 died during hospitalization (5.5%). The 30 day case-fatality rate according to educational level was 3.4% in tertiary, 4.7% in secondary, 11.9% in basic, 19.1% in none (p < 0.0001). Among patients surviving the first 30 days, the case fatality rate was 4.4%, 8.6%, 14.6% and 27.0%, respectively (p < 0.0001). The increased risk of death for groups with lower education compared with individuals with tertiary education, persisted in the multivariate analysis with a hazard ratio for secondary education 1.58 (95% confidence intervals (CI), 1.18-2.10); for basic education 1.90 (95% CI, 1.41-2.47) and for none 3.50 (95% CI, 2.35 5.21). CONCLUSIONS: A lower educational level was associated with a worse prognosis in patients with myocardial infarction, even after controlling for potential confounding factors. PMID- 26361018 TI - [Development of malignant tumors in patients with inflammatory bowel disease]. AB - BACKGROUND: The chronic inflammation of the intestinal mucosa, the extra intestinal manifestations of the disease and the immunosuppressive treatment of inflammatory bowel disease may increase cancer risk. AIM: To report the demographic and clinical features of patients with IBD who developed a malignant tumor. MATERIAL AND METHODS: Retrospective analysis of an IBD patient registry of a private clinic, diagnosed between 1976 and 2014. RESULTS: 437 subjects were included, aged 15-88 years (58% women). Seventy two percent of patients had ulcerative colitis. The median time of follow up was 6 years. Ten patients (2.3%) developed a malignant tumor. In four, the tumor could be related to IBD (two colorectal cancers, one cholangiocarcinoma and one chronic myeloid leukemia (CML)). Two of 45 patients treated with biological therapy developed a tumor (CML and hypernephroma). Three of 170 patients on immunosuppressive treatment developed tumors. Only one had a tumor possibly related with the use of azathioprine (non-melanoma skin cancer). In only two patients, the treatment was changed at the time of their cancer diagnosis, from immunosuppressive medications to mesalamine. CONCLUSIONS: Only a small proportion of these patients with IBD developed a malignant tumor. The treatment of IBD has to be determined by the severity of the disease and not by the fear of developing a neoplasia. Following recommendations is fundamental to decrease the possibility of developing this complication. PMID- 26361019 TI - [Students' perceptions comparing standardized and non-standardized oral exams in internal medicine]. AB - BACKGROUND: Oral examinations are a useful tool to appraise certain medical skills compared to other examinations. However, they have some disadvantages that might be reduced with standardization. AIM: To compare students' perception comparing a standardized oral exam (SOE) versus a traditional, non-standardized oral exam (NSOE). MATERIAL AND METHODS: During the first semester of 2013 a NSOE was applied to internal medicine undergraduate students. During the second semester, a SOE was applied. An anonymous and voluntary perception questionnaire, consisting in 10 questions based on a 5-level Likert scale, was answered by these students. Statistical analysis was done using the Mann-Whitney U test. RESULTS: Among the 118 students, 50.8% were evaluated using NSOE and 49.2% using SOE. Questionnaire response rate was 84%. Among respondents, 52% took the SOE and 48%, the NSOE. Students evaluated using SOE perceived that the degree of complexity of clinical cases was similar for all examinees (p < 0.05), that exam duration was standardized (p < 0.05), and that grades obtained were less influenced by the clinical site where the exam was taken (p < 0.05). However, anxiety level remained high in both groups, as well as the overall satisfaction experience. CONCLUSIONS: Standardization of an oral examination improves the perception of medical students about levels of difficulty, duration and external influences on the final grade. PMID- 26361020 TI - [Squamous cell carcinoma of the lip survival rate]. AB - BACKGROUND: Squamous Cell Carcinoma (SCC) of the lip represents about 20% of all oral carcinomas. It is more common in men, peaking during their sixth and seventh decade, and is more prevalent in the lower lip. AIM: To determine the five years survival rate of Chilean patients with lip SCC. MATERIAL AND METHODS: The registry of the Chilean National Cancer Institute was reviewed to retrieve the clinical records of patients with lip SCC. Information about age, sex, alcohol consumption, smoking, degree of pathological differentiation, lip location, type of treatment and metastases was recorded. Survival was determined with death certificates from the National Identification Service. RESULTS: Seventy four patients were identified. Their 5-year survival was 73%. CONCLUSIONS: The survival rate of this group of patients is lower than that of patients from Unites States who have an 89.5% survival, according to the Surveillance, Epidemiology, and End Results Program of the North American National Cancer Institute. PMID- 26361021 TI - [An exploratory study of functional literacy on health care behaviors in Chile]. AB - BACKGROUND: Health Literacy is the set of skills that constitute the ability to perform reading and numerical tasks to function in the health care environment. People with functional illiteracy are unable to understand written documents and therefore sanitary information. AIM: To explore the effects of functional illiteracy on personal health care behaviors in Chile. MATERIAL AND METHODS: Using the Chilean Social Characterization Survey of 2006, respondents were separated into those that had read a book in the last year and those that had not as a proxy variable for functional literacy. Using econometric models, the impact of this variable on having a Papanicolaou (PAP) smear done and consulting in primary health clinics rather than in emergency services, was explored. RESULTS: The survey is nationally representative, and 76% interviewees declared not having read a book in the last year. Probability of having a PAP smear done during the last three years was higher among women who had read a book with an OR of 1.19 (1.15-1.25). Likewise, the probability of consulting in emergency services rather than in primary health clinics was lower among those who had read a book with an OR of 0.85 (0.80-0.91). CONCLUSIONS: This study provides evidence of possible impacts of low functional literacy in health care behaviors in the Chilean population. PMID- 26361022 TI - [Plasma ghrelin levels in the late postoperative period of vertical sleeve gastrectomy]. AB - BACKGROUND: Plasma ghrelin levels may decrease after vertical sleeve gastrectomy, probably due to the excision of a large portion of the gastric fundus. It is worth exploring the long term effects of this surgical procedure on ghrelin levels and their associations with changes in body weight. AIM: To assess ghrelin levels and changes in body weight, one and five years after a vertical sleeve gastrectomy. MATERIAL AND METHODS: Plasma ghrelin was measured prior to gastric sleeve gastrectomy, immediately after surgery and BMI was controlled at one and five years of the postoperative period in 16 and 10 obese patients, respectively. Mean baseline body mass index was 40.4 +/- 6 kg/m2. RESULTS: Ghrelin decreased in 10 patients and increased in six during the long term postoperative period. At one year, mean body mass index decreased to 25.1 +/- 1.6 kg/m2. Changes in weight and ghrelin levels had no relationship whatsoever. At five years of follow up, body mass index had increased to 29.9 +/- 2.5 kg/m2, again without any association with ghrelin levels. CONCLUSIONS: Ghrelin levels may decrease or increase after vertical sleeve gastrectomy and have no association with changes in body weight. PMID- 26361024 TI - [Frequency of holoprosencephaly in Chile]. AB - BACKGROUND: Holoprosencephaly is a structural anomaly of the brain that consists in a defect of the prosencephalon development that leads to face and neurological defects of variable intensity. AIM: To estimate holoprosencephaly prevalence at birth. PATIENTS AND METHODS: All cases of holoprosencephaly, born alive or stillbirths, registered in the 15 Chilean Hospitals of the Latin American Collaborative Study of Congenital Malformations (ECLAMC) between 1972 and 2012, were studied. Craniofacial and other anomalies found in newborns affected by holoprosencephaly are described. RESULTS: Fifty five cases of holoprosencephaly (58% males) were found among the 798.222 registered births (rendering a prevalence at birth of 0.69 per 10.000 newborns). The most common cranial defect was medial cleft lip with cleft palate (27.3%), bilateral cleft lip (11%) or both (38.2%), cyclopia (14%), single nostril (10.9%) and proboscis (9.1%). Eleven percent cases had a trisomy 13. A slight increase in prevalence over time was observed. CONCLUSIONS: Holoprosencephaly has a low frequency in Chile and is associated to trisomy 13. The increase in prevalence could be explained by a better prenatal diagnosis (ultrasonography). PMID- 26361023 TI - [Delay in the diagnosis of Parkinson's disease in a Chilean public hospital]. AB - BACKGROUND: Early diagnosis is fundamental in patients with Parkinson's disease (PD) to improve their quality of life. AIM: To determine the latency in the diagnosis of Parkinson's disease (PD) after the onset of motor symptoms. PATIENTS AND METHODS: Prospective study carried out during 16 months in a public hospital. Two hundred newly diagnosed patients aged 41 to 90 years (50% women), were included and analyzed. RESULTS: The lapse between the first symptom -more commonly tremor- and the diagnosis made by a neurologist ranged from 1 to 84 months (19.1 +/- 13.8). In 39% of patients, it was done in the first year, in 26% during the second year and in 35% of patients, it took more than two years. The referral by a general practitioner had a delay ranging from 1 to 36 months. Sixty nine and 95% of patients were evaluated within the first 6 months after referral if they came from primary care or the same hospital, respectively. Twenty six percent of patients were classified in stages III to V of Hoehn & Yahr's staging and the Parkinson's Disease Rating Scale motor examination ranged from 5 to 81 points, mean 24 (+/- 12.8). CONCLUSIONS: The diagnosis of PD has a delay in a public hospital that could be influenced by the referral system. PMID- 26361025 TI - [Comparison of two methods to assess causality of adverse drug reactions]. AB - BACKGROUND: Assessment of causality is an essential part of pharmacological surveillance. AIM: To compare the causality assessment of suspected adverse drug reactions (ADRs) using algorithms proposed by Karch-Lasagna (K & L) and the World Health Organization (WHO). MATERIAL AND METHODS: All spontaneous reports of suspected ADRs in a pediatric ward of a regional hospital were included. Causality was categorized as definitive, probable, possible, conditional or unlikely. The agreement between K & L and WHO algorithms was assessed using binomial test proportions and kappa coefficients. RESULTS: One hundred thirty reports of ADRs in 126 patients aged 2 to 11 years were analyzed. The suspected medications were antineoplastic drugs in 59% of cases and antimicrobials in 23%. The most common affected system was the skin and appendages in 35%. Using K & L algorithm, causality was categorized as definitive in 10% of cases, probable in 28.5%, possible in 35.4%, conditional in 23.1% and unlikely in 3.0%. Using WHO algorithm, the figures were 2.3, 34.6, 59.2, 2.3 and 1.5%, respectively. The degree of agreement between K & L and WHO algorithms was 32.3% (kappa = 0.004). CONCLUSIONS: K & L attributed a higher level of ADR causality than WHO algorithm. PMID- 26361026 TI - [An update on postpartum depression]. AB - Postpartum depression (PPD) is a common condition worldwide and most of the available information is about treatment rather than prevention. This paper is an update on prevention and treatment of PPD. A simple review of the literature and a critical review of papers' methodology and conclusions was carried out. There is a consensus of the preeminence of psychosocial factors in the genesis of PPD. Considering the complications when the condition is not treated, it is of the utmost importance to implement early detection and management strategies. The use of psychosocial preventive interventions is an alternative that has support in the literature and should be seriously considered. PMID- 26361027 TI - [Thrombolytic therapy for submassive/ intermediate risk Pulmonary Embolism Evidence and suggestions after PEITHO trial]. AB - Therapy for submassive pulmonary embolism (intermediate risk), remains controversial. New evidence has appeared that may help us in the process of decision making. We review the relevant literature, outline prognostic factors, and discuss current recommendations and controversies regarding the available alternatives such as systemic and catheter-directed thrombolytic use. PMID- 26361028 TI - [A brief magnetic resonance imaging protocol for spondyloarthritis]. AB - Spondyloarthritis is a group of diseases that seriously hampers quality of life. Diagnostic criteria, in which images play an important role, have evolved over time. The most recent diagnostic criteria, published in 2009, included magnetic resonance imaging (MRI) of the sacroiliac joints for the first time. This technique achieves an early diagnosis and provides a useful tool for the evaluation and prediction of response to biological therapy. Herein, we describe the different MRI findings in spondyloarthropathies. We also highlight the use of a protocol that includes the sacroiliac joints and spine and that does not consider the routine use of paramagnetic contrast. PMID- 26361029 TI - [History and functions of Chilean ophthalmologic primary care units]. AB - The access to ophthalmological care in Chile has been historically a problem. Only at the end of the twentieth century concrete solutions were promoted. In 1960, Primary Care Ophthalmologic Units were created to ease the access to ophthalmology, due to the efforts of Professor Juan Arentsen. Their functioning was organized and standardized subsequently using a model proposed by the Chilean Ophthalmologic Society, leading to a better patient flow and reducing waiting lists. These units became an innovative initiative to reduce the gaps in Chilean public health, optimizing the professional and infrastructural assets of the public health care system and achieving a new organization for the ophthalmological health care net. PMID- 26361030 TI - [Why should we remain in service when facing the threat of Ebola virus infection?: Some reflections]. AB - Currently, the Ebola virus has been classified by the WHO as "an international public health emergency" that has highlighted among other things, the enormous importance of proper and timely medical care. However, the complexity of this new health scenario, mainly due to personal risk in the event of infection, means that professionals are directly faced with situations of great ethical conflict since there is a competition between their duties to patients, colleagues, society and those directed to their own safety. The reasons given by those professionals who respond positively to the duties of their patients have been categorized into three items, namely: professional ethics, the need to help and work ethics. The philosophical foundations of these responses find their roots in the compassion and sense of responsibility that arise when we face helplessness. PMID- 26361031 TI - [Academic achievement, engagement and burnout among first year medical students]. AB - BACKGROUND: Stress may affect the sense of wellbeing and academic achievement of university students. AIM: To assess the relationship of academic engagement and burnout with academic achievement among first year medical students. MATERIAL AND METHODS: The Utrecht Work Engagement Scale-Student and Maslach Burnout Inventory Student Survey (MBI-SS) were applied to 277 first year medical students of four universities. Their results were correlated with the grades obtained in the different courses. RESULTS: Moderately high engagement and low burnout levels were detected. There was a high level of satisfaction with studies and a moderate exhaustion level. Academic achievement was associated with the degree of engagement with studies but not with burnout. Conglomerate analysis detected a group of students with high levels of wellbeing, characterized by high levels of academic engagement and low burnout. Other group had moderate levels of engagement and lack of personal fulfilment. Other group, identified as extenuated, had high levels of personal exhaustion and depersonalization. Finally the disassociated group had a low academic engagement, low emotional exhaustion, high levels of depersonalization and lack of personal fulfillment. CONCLUSIONS: Academic achievement is associated with the level of engagement with studies but not with burnout. PMID- 26361032 TI - [Insulin autoimmune syndrome: Report of two cases]. AB - Insulin autoimmune syndrome (IAS) is characterized by spontaneous hypoglycemia with extremely high insulin levels and the presence of circulating autoantibodies against insulin, in patients who have never been exposed to exogenous insulin. We report two patients with the syndrome. A 36 years old male presenting with hypoglycemia in the emergency room had an oral glucose tolerance test showed basal and 120 min glucose levels of 88 and 185 mg/dl. The basal and 120 min insulin levels were 2,759 and 5,942 MUUI/ml. The presence of an insulin secreting tumor was discarded. Anti-insulin antibodies were positive. He was successfully treated with a diet restricted in carbohydrates and frequent meals in small quantities. A 65 years old female presenting with hypoglycemia in the emergency room had the fasting insulin levels of 1,910 uUI/ml. No insulin secreting tumor was detected by images and anti-insulin antibodies were positive. The polyethylene glycol precipitation test showed a basal and after exposition insulin level 1,483 and 114 uUI/ml, respectively. She responded partially to diet and acarbose and required the use of prednisone with a good clinical response. PMID- 26361033 TI - [Peritoneal myofibroblastic tumor successfully treated with infliximab: Report of one case]. AB - Myofibroblastic tumor (MIT) is characterized by the infiltration of different organs, most commonly the lungs, with nodular lesions composed of myofibroblasts and inflammatory cells, which can be identified by specific patterns in the immunohistochemical studies. When it involves the peritoneum it is difficult to eradicate, tends to relapse and it has an invasive behavior, requiring its differentiation from peritoneal carcinomatosis. Treatment may be surgical excision, the use of non-steroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids. We report a 30 years old female with an unremarkable medical history, presenting with abdominal pain and progressive abdominal distention. A CT scan revealed multiple peritoneal nodular lesions. A surgical biopsy was reported as a myofibroblast and inflammatory cell infiltrate. Immunohistochemical staining was consistent with MIT. Given the extensive involvement of the peritoneum surgical therapy was not considered appropriate and treatment with NSAID and glucocorticoids was started. No response was observed after 6 months, therefore infliximab therapy was started. After 10 months of follow-up the patient is well, returned to normal life, ascites improved and resolved and CT scan showed partial regression or stabilization of the lesions. PMID- 26361034 TI - [Creativity and Neuroscience: An essential binomial in educational context]. PMID- 26361035 TI - [Neuroscience and physical activity: A new perspective in educational context]. PMID- 26361036 TI - [An appraisal of the SF-12 Questionnaire]. PMID- 26361037 TI - [An appraisal of the SF12 Questionnaire (Reply)]. PMID- 26361038 TI - Obesity and Pro12Ala Polymorphism of Peroxisome Proliferator-Activated Receptor Gamma Gene in Healthy Adults: A Systematic Review and Meta-Analysis. AB - BACKGROUND: The aim of this systematic review was to evaluate the relationship between obesity and peroxisome proliferator-activated receptor-gamma (PPARx03B3;) Pro12Ala polymorphism in healthy adults. SUMMARY: Weighted mean differences (WMDs) of body mass index (BMI) were calculated for different inheritance models and subgroups. Fifty-six studies were eligible for inclusion in the meta analysis. The result shows that the Ala allele of this polymorphism was associated with increased WMD in mean BMI (WMD = 0.29, 95% CI 0.10-0.48, p = 0.003). The Ala carriers were associated with increased WMD in mean BMI values in both genders and in the Caucasian subgroup. The associations were seen among people with higher levels of BMI (BMI >=35). MESSAGE: The Ala allele of the PPARx03B3; Pro12Ala polymorphism in healthy adults was associated with increased BMI under a dominant model of inheritance. PMID- 26361039 TI - Four new actinide chalcogenides Ba2Cu4USe6, Ba2Cu2ThSe5, Ba2Cu2USe5, and Sr2Cu2US5: crystal structures and physical properties. AB - Four new actinide chalcogenides-namely, Ba2Cu4USe6, Ba2Cu2ThSe5, Ba2Cu2USe5, and Sr2Cu2US5-were synthesized via solid-state methods at 1173 K. Single-crystal X ray diffraction studies show that Ba2Cu4USe6 crystallizes in a new structure type in space group C2h5-P21/c of the monoclinic system, whereas the three other compounds are isostructural and adopt the Ba2Cu2US5 structure type in space group C2h3-C2/m, also of the monoclinic system. These Ak/Cu/An/Q structures (Ak = alkaline-earth metal; An = actinide; Q = chalcogen) have no short Q-Q interactions and, hence, are charge-balanced with Ak2+, Cu1+, An4+, and Q2-. Crystal structures of all these compounds are two-dimensional and feature layers that are separated by Ba2+ cations. The compositions of these layers differ. In the structure of Ba2Cu4USe6, the infinity2[Cu4USe64-] layers comprising USe6 octahedra and CuSe4 tetrahedra stack perpendicular to the a-axis. These infinity2[Cu4USe64-] layers show short Cu-Cu interactions. In the three isostructural Ak2Cu2AnQ5 compounds, AnQ6 octahedra and CuQ4 tetrahedra are connected along the c-axis in the sequence "...oct tet tet oct tet tet..." to form the infinity2[Cu2AnQ54-] layers. Resistivity, optical, and DFT calculations show semiconducting behavior for these compounds. PMID- 26361041 TI - Facilitating the implementation of the American College of Surgeons/Association of Program Directors in Surgery phase III skills curriculum: training faculty in the assessment of team skills. AB - BACKGROUND: Effective teamwork is critical to safety in the operating room; however, implementation of phase III of the American College of Surgeons (ACS) and Association of Program Directors in Surgery (APDS) Curriculum that focuses on team-based skills remains worryingly low. Training and assessing the complexities of teamwork is challenging. The objective of this study was to establish guidelines and recommendations for training faculty in assessing/debriefing team skills. METHODS: A multistage survey-based consensus study was completed by 108 experts responsible for training and assessing surgical residents from the ACS Accredited Educational Institutes. RESULTS: Experts agreed that a program to teach faculty to assess team-based skills should include training in the recognition of teamwork skills, practice rating these skills, and training in the provision of feedback/debriefing. Agreement was reached that faculty responsible for conducting team-based skills assessment should be revalidated every 2 years and stringent proficiency criteria should be met. CONCLUSIONS: Faculty development is critical to ensure high-quality, standardized training and assessment. Training faculty to assess team-based skills has the potential to facilitate the effective implementation of phase III of the ACS and APDS Curriculum. PMID- 26361040 TI - HIF-1alpha Plays a Critical Role in the Gestational Sidestream Smoke-Induced Bronchopulmonary Dysplasia in Mice. AB - RATIONALE: Smoking during pregnancy increases the risk of bronchopulmonary dysplasia (BPD) and, in mice, gestational exposure to sidestream cigarette smoke (SS) induces BPD-like condition characterized by alveolar simplification, impaired angiogenesis, and suppressed surfactant protein production. Normal fetal development occurs in a hypoxic environment and nicotinic acetylcholine receptors (nAChRs) regulate the hypoxia-inducible factor (HIF)-1alpha that controls apoptosis and angiogenesis. To understand SS-induced BPD, we hypothesized that gestational SS affected alveolar development through HIF-1alpha. METHODS: Pregnant BALB/c mice were exposed to air (control) or SS throughout the gestational period and the 7-day-old lungs of the progeny were examined. RESULTS: Gestational SS increased apoptosis of alveolar and airway epithelial cells. This response was associated with increased alveolar volumes, higher levels of proapoptotic factors (FOXO3a, HIPK2, p53, BIM, BIK, and BAX) and the antiangiogenic factor (GAX), and lower levels of antiapoptotic factors (Akt-PI3K, NF-kappaB, HIF-1alpha, and Bcl-2) in the lung. Although gestational SS increased the cells containing the proangiogenic bombesin-like-peptide, it markedly decreased the expression of its receptor GRPR in the lung. The effects of SS on apoptosis were attenuated by the nAChR antagonist mecamylamine. CONCLUSIONS: Gestational SS-induced BPD is potentially regulated by nAChRs and associated with downregulation of HIF-1alpha, increased apoptosis of epithelial cells, and increased alveolar volumes. Thus, in mice, exposure to sidestream tobacco smoke during pregnancy promotes BPD-like condition that is potentially mediated through the nAChR/HIF-1alpha pathway. PMID- 26361043 TI - Immune recognition of excretory and secretory products of the filarial nematode Onchocerca ochengi in cattle and human sera. AB - Excretory-secretory (ES) products of nematodes and other helminths are the first molecules to interact with cell surfaces and soluble proteins within the host. In the present study, ES products of the filarial nematode Onchocerca ochengi were investigated as a model for Onchocerca volvulus, the causative agent of river blindness. These products were collected from adult and larval stages in vitro over a period of 7 days, to compare their immunological recognition in cattle and human sera, infected with species of Onchocerca. From the 156 sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) ES products or extracts, protein bands showed different patterns between female and male products. A comparison of antibody recognition of the different ES products by sera from infected cattle and humans, when analysed by enzyme-linked immunosorbent assay (ELISA), revealed a relatively higher reactivity of the female somatic extract to human and cattle sera compared to ES products of both genders. Nevertheless, similar reactivity of the O. ochengi male and female ES products to human and cattle sera was noticed. As a result, the interaction of ES products with the surface of the host and immune system often led to host responses, including the generation of antibodies. The O. ochengi ES products are therefore good sources of potential immunogenic proteins. The identification of these ES products is in progress, with the aim of developing vaccine candidates against human onchocerciasis. PMID- 26361042 TI - PD-1 Blockade Can Restore Functions of T-Cells in Epstein-Barr Virus-Positive Diffuse Large B-Cell Lymphoma In Vitro. AB - Epstein-Barr virus-positive diffuse large B-cell lymphoma (EBV+DLBCL) is an aggressive malignancy that is largely resistant to current therapeutic regimens, and is an attractive target for immune-based therapies. Anti-programmed death-1 (PD-1) antibodies showed encouraging anti-tumor effects in both preclinical models and advanced solid and hematological malignancies, but its efficacy against EBV+DLBCL is unknown. Herein, we performed experiments using co-culture system with T cells and lymphoma cell lines including EBV+DLBCL and EBV-DLBCL [including germinal center B-cell like (GCB)-DLBCL and non-GCB-DLBCL] in vitro. We show that lymphoma cells augmented the expression of PD-1 on T cells, decreased the proliferation of T cells, and altered the secretion of multiple cytokines. However, through PD-1 blockade, these functions could be largely restored. Notbaly, the effect of PD-1 blockade on antitumor immunity was more effective in EBV+DLBCL than that in EBV-DLBCL in vitro. These results suggest that T-cell exhaustion and immune escape in microenvironment is one of the mechanisms underlying DLBCL; and PD-1 blockade could present as a efficacious immunotherapeutic treatment for EBV+DLBCL. PMID- 26361044 TI - Functional Characterization of Hevea brasiliensis CRT/DRE Binding Factor 1 Gene Revealed Regulation Potential in the CBF Pathway of Tropical Perennial Tree. AB - Rubber trees (Hevea brasiliensis) are susceptible to low temperature and therefore are only planted in the tropical regions. In the past few decades, although rubber trees have been successfully planted in the northern margin of tropical area in China, they suffered from cold injury during the winter. To understand the physiological response under cold stress, we isolated a C-repeat binding factor 1 (CBF1) gene from the rubber tree. This gene (HbCBF1) was found to respond to cold stress but not drought or ABA stress. The corresponding HbCBF1 protein showed CRT/DRE binding activity in gel shift experiment. To further characterize its molecular function, the HbCBF1 gene was overexpressed in Arabidopsis. The HbCBF1 over expression (OE) line showed enhanced cold resistance and relatively slow dehydration, and the expression of Arabidopsis CBF pathway downstream target genes, e.g. AtCOR15a and AtRD29a, were significantly activated under non-acclimation condition. These data suggest HbCBF1 gene is a functional member of the CBF gene family, and may play important regulation function in rubber tree. PMID- 26361045 TI - PD-L1 is remarkably over-expressed in EBV-associated pulmonary lymphoepithelioma like carcinoma and related to poor disease-free survival. AB - BACKGROUD: Programmed cell death-ligand 1 (PD-L1) and driver mutations are commonly seen in non-small-cell lung cancer (NSCLC). However, the prevelance of PD-L1 over-expression and its prognostic value in Epstein-Barr virus (EBV) associated pulmonary lymphoepithelioma-like carcinoma (LELC) remains poorly understood. METHODS: A total of 214 NSCLC patients and 113 surgically treated pulmonary LELC patients were included. Paraffin-embedded tumor sections were stained with PD-L1 antibody. Correlations between PD-L1 expression and clinicopathological features as well as survival outcomes were analyzed. RESULTS: The frequency of PD-L1 over-expression in NSCLC was 51.4%. No significant association was observed between common driver mutations and PD-L1 over expression. Remakably, the positive rate of PD-L1 in pulmonary LELC was 74.3%. High PD-L1 expression was associated with impaired disease-free survival (DFS) compared with low PD-L1 expression (p = 0.008). Multivariate analysis shows that PD-L1 expression level, N stage and M stage were independent prognostic factors for DFS. N stage and M stage but not PD-L1 expression level were significantly associated with overall survival (OS). CONCLUSIONS: PD-L1 over-expression was not related to common driver mutations in NSCLC. Pulmonary LELC have remarkably high incidence of PD-L1 expression. PD-L1 was a negative prognostic factor for DFS in surgically resected pulmonary LELC. These findings may provide a rationale for immunotarget therapy in this virus-associated lung cancer. PMID- 26361047 TI - Range and Frequency of Africanized Honey Bees in California (USA). AB - Africanized honey bees entered California in 1994 but few accounts of their northward expansion or their frequency relative to European honey bees have been published. We used mitochondrial markers and morphometric analyses to determine the prevalence of Africanized honeybees in San Diego County and their current northward progress in California west of the Sierra Nevada crest. The northernmost African mitotypes detected were approximately 40 km south of Sacramento in California's central valley. In San Diego County, 65% of foraging honey bee workers carry African mitochondria and the estimated percentage of Africanized workers using morphological measurements is similar (61%). There was no correlation between mitotype and morphology in San Diego County suggesting Africanized bees result from bidirectional hybridization. Seventy percent of feral hives, but only 13% of managed hives, sampled in San Diego County carried the African mitotype indicating that a large fraction of foraging workers in both urban and rural San Diego County are feral. We also found a single nucleotide polymorphism at the DNA barcode locus COI that distinguishes European and African mitotypes. The utility of this marker was confirmed using 401 georeferenced honey bee sequences from the worldwide Barcode of Life Database. Future censuses can determine whether the current range of the Africanized form is stable, patterns of introgression at nuclear loci, and the environmental factors that may limit the northern range of the Africanized honey bee. PMID- 26361046 TI - Myosin 1b Regulates Amino Acid Transport by Associating Transporters with the Apical Plasma Membrane of Kidney Cells. AB - Amino acid transporters (AATers) in the brush border of the apical plasma membrane (APM) of renal proximal tubule (PT) cells mediate amino acid transport (AAT). We found that the membrane-associated class I myosin myosin 1b (Myo1b) localized at the apical brush border membrane of PTs. In opossum kidney (OK) 3B/2 epithelial cells, which are derived from PTs, expressed rat Myo1b-GFP colocalized in patched microvilli with expressed mouse V5-tagged SIT1 (SIT1-V5), which mediates neutral amino acid transport in OK cells. Lentivirus-mediated delivery of opossum Myo1b-specific shRNA resulted in knockdown (kd) of Myo1b expression, less SIT1-V5 at the APM as determined by localization studies, and a decrease in neutral AAT as determined by radioactive uptake assays. Myo1b kd had no effect on Pi transport or noticeable change in microvilli structure as determined by rhodamine phalloidin staining. The studies are the first to define a physiological role for Myo1b, that of regulating renal AAT by modulating the association of AATers with the APM. PMID- 26361048 TI - Evidence-Based Practice: The Psychology of EBP Implementation. AB - Evidence-based practice (EBP) is an approach used in numerous professions that focuses attention on evidence quality in decision making and action. We review research on EBP implementation, identifying critical underlying psychological factors facilitating and impeding its use. In describing EBP and the forms of evidence it employs, we highlight the challenges individuals face in appraising evidence quality, particularly that of their personal experience. We next describe critical EBP competencies and the challenges underlying their acquisition: foundational competencies of critical thinking and domain knowledge, and functional competencies such as question formulation, evidence search and appraisal, and outcome evaluation. We then review research on EBP implementation across diverse fields from medicine to management and organize findings around three key contributors to EBP: practitioner ability, motivation, and opportunity to practice (AMO). Throughout, important links between psychology and EBP are highlighted, along with the contributions psychological research can make to further EBP development and implementation. PMID- 26361049 TI - Beyond Words: How Humans Communicate Through Sound. AB - Every day we communicate using complex linguistic and musical systems, yet these modern systems are the product of a much more ancient relationship with sound. When we speak, we communicate not only with the words we choose, but also with the patterns of sound we create and the movements that create them. From the natural rhythms of speech, to the precise timing characteristics of a consonant, these patterns guide our daily communication. By examining the principles of information processing that are common to speech and music, we peel back the layers to reveal the biological foundations of human communication through sound. Further, we consider how the brain's response to sound is shaped by experience, such as musical expertise, and implications for the treatment of communication disorders. PMID- 26361050 TI - Toward a Social Psychology of Race and Race Relations for the Twenty-First Century. AB - The United States, like many nations, continues to experience rapid growth in its racial minority population and is projected to attain so-called majority-minority status by 2050. Along with these demographic changes, staggering racial disparities persist in health, wealth, and overall well-being. In this article, we review the social psychological literature on race and race relations, beginning with the seemingly simple question: What is race? Drawing on research from different fields, we forward a model of race as dynamic, malleable, and socially constructed, shifting across time, place, perceiver, and target. We then use classic theoretical perspectives on intergroup relations to frame and then consider new questions regarding contemporary racial dynamics. We next consider research on racial diversity, focusing on its effects during interpersonal encounters and for groups. We close by highlighting emerging topics that should top the research agenda for the social psychology of race and race relations in the twenty-first century. PMID- 26361052 TI - Psychology of Habit. AB - As the proverbial creatures of habit, people tend to repeat the same behaviors in recurring contexts. This review characterizes habits in terms of their cognitive, motivational, and neurobiological properties. In so doing, we identify three ways that habits interface with deliberate goal pursuit: First, habits form as people pursue goals by repeating the same responses in a given context. Second, as outlined in computational models, habits and deliberate goal pursuit guide actions synergistically, although habits are the efficient, default mode of response. Third, people tend to infer from the frequency of habit performance that the behavior must have been intended. We conclude by applying insights from habit research to understand stress and addiction as well as the design of effective interventions to change health and consumer behaviors. PMID- 26361053 TI - In Pursuit of Three Theories: Authoritarianism, Relative Deprivation, and Intergroup Contact. AB - Throughout my career, I have pursued three theories related to intergroup prejudice--each with a different mentor. Each theory and its supporting research help us to understand prejudice and ways to ameliorate the problem. This autobiographical review article summarizes some of the advances in these three areas during the past six decades. For authoritarianism, the article advocates removing political content from its measurement, linking it with threat and dismissive-avoidant attachment, and studying how authoritarians avoid intergroup contact. Increased work on relative deprivation made possible an extensive meta analysis that shows the theory, when appropriately measured, has far broader effects than previously thought. Increased research attention to intergroup contact similarly made possible a meta-analysis that established the pervasive effectiveness of intergroup contact to reduce prejudice under a wide range of conditions. The article closes by demonstrating how the three theories relate to each other and contribute to our understanding of prejudice and its reduction. PMID- 26361054 TI - Stereotype Threat. AB - When members of a stigmatized group find themselves in a situation where negative stereotypes provide a possible framework for interpreting their behavior, the risk of being judged in light of those stereotypes can elicit a disruptive state that undermines performance and aspirations in that domain. This situational predicament, termed stereotype threat, continues to be an intensely debated and researched topic in educational, social, and organizational psychology. In this review, we explore the various sources of stereotype threat, the mechanisms underlying stereotype-threat effects (both mediators and moderators), and the consequences of this situational predicament, as well as the means through which society and stigmatized individuals can overcome the insidious effects of stereotype threat. Ultimately, we hope this review alleviates some of the confusion surrounding stereotype threat while also sparking further research and debate. PMID- 26361055 TI - Faceted nanostructure arrays with extreme regularity by self-assembly of vacancies. AB - Semiconductor quantum dots and wires are important building blocks for future electronic and optoelectronic devices. The common way of producing semiconductor nanostructures is by molecular beam epitaxy (MBE). In this additive growth process atoms are deposited onto crystalline surfaces and self-assemble into 3D structures. Here we present a subtractive process, in which surface vacancies are created by ion impacts. On terraces of crystalline surfaces their nucleation forms depressions which coarsen and finally lead to a self-organized 3D morphology. It is shown that this kind of spontaneous pattern formation is inherent to the ion induced erosion process on crystalline surfaces and is analogous to 3D growth by MBE. However, novel facets are found due to slightly different energetics and kinetics of ad-atoms and surface vacancies, especially at Ehrlich-Schwoebel step-edge barriers. Depending on the crystal orientation, three-fold, four-fold, six-fold symmetry, as well as extremely regular periodic nanogrooves can be produced on different orientations of group IV (Si, Ge) and III-V (GaAs, InAs) semiconductors. PMID- 26361051 TI - Remembering Preservation in Hippocampal Amnesia. AB - The lesion-deficit model dominates neuropsychology. This is unsurprising given powerful demonstrations that focal brain lesions can affect specific aspects of cognition. Nowhere is this more evident than in patients with bilateral hippocampal damage. In the past 60 years, the amnesia and other impairments exhibited by these patients have helped to delineate the functions of the hippocampus and shape the field of memory. We do not question the value of this approach. However, less prominent are the cognitive processes that remain intact following hippocampal lesions. Here, we collate the piecemeal reports of preservation of function following focal bilateral hippocampal damage, highlighting a wealth of information often veiled by the field's focus on deficits. We consider how a systematic understanding of what is preserved as well as what is lost could add an important layer of precision to models of memory and the hippocampus. PMID- 26361056 TI - Supersensitive detection and discrimination of enantiomers by dorsal olfactory receptors: evidence for hierarchical odour coding. AB - Enantiomeric pairs of mirror-image molecular structures are difficult to resolve by instrumental analyses. The human olfactory system, however, discriminates (-) wine lactone from its (+)-form rapidly within seconds. To gain insight into receptor coding of enantiomers, we compared behavioural detection and discrimination thresholds of wild-type mice with those of DeltaD mice in which all dorsal olfactory receptors are genetically ablated. Surprisingly, wild-type mice displayed an exquisite "supersensitivity" to enantiomeric pairs of wine lactones and carvones. They were capable of supersensitive discrimination of enantiomers, consistent with their high detection sensitivity. In contrast, DeltaD mice showed selective major loss of sensitivity to the (+)-enantiomers. The resulting 10(8)-fold differential sensitivity of DeltaD mice to (-)- vs. (+) wine lactone matched that observed in humans. This suggests that humans lack highly sensitive orthologous dorsal receptors for the (+)-enantiomer, similarly to DeltaD mice. Moreover, DeltaD mice showed >10(10)-fold reductions in enantiomer discrimination sensitivity compared to wild-type mice. DeltaD mice detected one or both of the (-)- and (+)-enantiomers over a wide concentration range, but were unable to discriminate them. This "enantiomer odour discrimination paradox" indicates that the most sensitive dorsal receptors play a critical role in hierarchical odour coding for enantiomer identification. PMID- 26361057 TI - Adolescent Social Stress Produces an Enduring Activation of the Rat Locus Coeruleus and Alters its Coherence with the Prefrontal Cortex. AB - Early life stress is associated with the development of psychiatric disorders. Because the locus coeruleus-norepinephrine (LC-NE) system is a major stress response system that is implicated in psychopathology, developmental differences in the response of this system to stress may contribute to increased vulnerability. Here LC single unit and network activity were compared between adult and adolescent rats during resident-intruder stress. In some rats, LC and medial prefrontal cortex (mPFC) coherence was quantified. The initial stress tonically activated LC neurons and induced theta oscillations, while simultaneously decreasing LC auditory-evoked responses in both age groups. Stress increased LC-mPFC coherence within the theta range. With repeated exposures, adolescent LC neuronal and network activity remained elevated even in the absence of the stressor and were unresponsive to stressor presentation. In contrast, LC neurons of adult rats exposed to repeated social stress were relatively inhibited in the absence of the stressor and mounted robust responses upon stressor presentation. LC sensory-evoked responses were selectively blunted in adolescent rats exposed to repeated social stress. Finally, repeated stress decreased LC mPFC coherence in the high frequency range (beta and gamma) while maintaining strong coherence in the theta range, selectively in adolescents. Together, these results suggest that adaptive mechanisms that promote stress recovery and maintain basal activity of the brain norepinephrine system in the absence of stress are not fully developed or are vulnerable stress-induced impairments in adolescence. The resulting sustained activation of the LC-NE system after repeated social stress may adversely impact cognition and future social behavior of adolescents. PMID- 26361058 TI - SKA2 Methylation is Involved in Cortisol Stress Reactivity and Predicts the Development of Post-Traumatic Stress Disorder (PTSD) After Military Deployment. AB - Genomic variation in the SKA2 gene has recently been identified as a promising suicide biomarker. In light of its role in glucocorticoid receptor transactivation, we investigated whether SKA2 DNA methylation influences cortisol stress reactivity and is involved in the development of post-traumatic stress disorder (PTSD). Increased SKA2 methylation was significantly associated with lower cortisol stress reactivity in 85 healthy individuals exposed to the Trier Social Stress Test (B=-173.40, t=-2.324, p-value=0.023). Next, we observed that longitudinal decreases in SKA2 methylation after deployment were associated with the emergence of post-deployment PTSD symptoms in a Dutch military cohort (N=93; B=-0.054, t=-3.706, p-value=3.66 * 10(-4)). In contrast, exposure to traumatic stress during deployment by itself resulted in longitudinal increases in SKA2 methylation (B=0.037, t=4.173, p-value=6.98 * 10(-5)). Using pre-deployment SKA2 methylation levels and childhood trauma exposure, we found that the previously published suicide prediction rule significantly predicted post-deployment PTSD symptoms (AUC=0.66, 95% CI: 0.53-0.79) with an optimal sensitivity of 0.81 and specificity of 0.91. Permutation analysis using random methylation loci supported these findings. Together, these data establish the importance of SKA2 for cortisol stress responsivity and the development of PTSD and provide further evidence that SKA2 is a promising biomarker for stress-related disorders including PTSD. PMID- 26361059 TI - Endocannabinoid Modulation of Predator Stress-Induced Long-Term Anxiety in Rats. AB - Individuals who experience life-threatening psychological trauma are at risk of developing a series of chronic neuropsychiatric pathologies that include generalized anxiety, depression, and drug addiction. The endocannabinoid system has been implicated in the modulation of these responses by regulating the activity of the amygdala and the hypothalamic-pituitary-adrenal axis. However, the relevance of this signaling complex to the long-term consequences of traumatic events is unclear. Here we use an animal model of predatory stress induced anxiety-like behavior to investigate the role of the endocannabinoid system in the development of persistent anxiety states. Our main finding is that rats exposed to the fox pheromone 2,5-dihydro-2,4,5-trimethylthiazoline (TMT), a life-threatening stimulus for rodents, display a marked and selective increase in the mobilization of the endocannabinoid, 2-arachidonoyl-sn-glycerol (2-AG), in the amygdala. This effect lasts for at least 14 days after the stress has occurred. In addition, systemic or local pharmacological inhibition of monoacylglycerol lipase (MGL)-a lipid hydrolase that degrades 2-AG in presynaptic nerve terminals-elevates 2-AG levels and suppresses the anxiety-like behavior elicited by exposure to TMT. The results suggest that predator threat triggers long-term changes in 2-AG-mediated endocannabinoid signaling in the amygdala, and that pharmacological interventions targeting MGL might provide a therapeutic strategy for the treatment of chronic brain disorders initiated by trauma. PMID- 26361061 TI - Post-translational Introduction of D-Alanine into Ribosomally Synthesized Peptides by the Dehydroalanine Reductase NpnJ. AB - Ribosomally synthesized peptides are generally limited to L-amino acid building blocks. Given the advantageous properties of peptides containing D-amino acids such as stabilization of certain turns and against proteolytic degradation, methods to introduce D-stereocenters are valuable. Here we report the first in vitro reconstitution and characterization of a dehydrogenase that carries out the asymmetric reduction of dehydroalanine. NpnJA reduces dehydroalanine to D-Ala using NAPDH as cosubstrate. The enzyme displays high substrate tolerance allowing introduction of D-Ala into a range of non-native substrates. In addition to the in vitro reactions, we describe five examples of using Escherichia coli as biosynthetic host for D-alanine introduction into ribosomal peptides. A deuterium label-based coupled-enzyme assay was used to rapidly determine the stereochemistry of the newly installed alanine. PMID- 26361060 TI - Randomized Placebo-Controlled Trial of Methylphenidate or Galantamine for Persistent Emotional and Cognitive Symptoms Associated with PTSD and/or Traumatic Brain Injury. AB - We report findings from a 12-week randomized double-blinded placebo-controlled trial of methylphenidate or galantamine to treat emotional and cognitive complaints in individuals (n=32) with a history of PTSD, TBI, or both conditions. In this small pilot study, methylphenidate treatment was associated with clinically meaningful and statistically significant improvement compared with placebo on the primary outcome, a measure of cognitive complaints (Ruff Neurobehavioral Inventory-Postmorbid Cognitive Scale), as well as on the secondary outcomes reflecting post-concussive (Rivermead Post Concussive Symptom Questionnaire) and post-traumatic stress symptoms (Posttraumatic Stress Disorder Checklist). Treatment was well tolerated. These results suggest the need for a larger RCT to replicate and confirm these findings. Design considerations for such a trial should include the need for multiple sites to facilitate adequate recruitment and extension of the treatment and follow-up periods. PMID- 26361062 TI - The post-stroke depression and its impact on functioning in young and adult stroke patients of a rehabilitation unit. AB - BACKGROUND: Stroke is a leading cause of disability and a major public health problem. AIMS: To determine frequency and degree of post-stroke depression (PSD) and its impact on functioning in young and adult stroke patients in a rehabilitation unit. METHOD: The study included 72 stroke patients (aged 29-59 years) who were attending rehabilitation. The patients were assessed for depressive symptoms by Beck Depression Inventory (BDI), and their functioning by using the Stroke Impact Scale (SIS) and the Barthel Index of Activities of Daily Living (ADL). RESULTS: Forty-eight patients had different degrees of depression: borderline clinical depression (13.8%), moderate depression (34.7%), severe depression (15.2%) or extreme depression (2.9%). There were no significant differences of BDI scores in 30-39, 40-49 and 50-59 years groups. Statistically significant correlations were between BDI score and SIS score, between BDI score and ADL index, and between SIS score and ADL index in men, women and total study patients. CONCLUSIONS: More than half of the PSD patients had a moderate degree of depression. Significant correlations were noticed between depressive symptoms and functional status evaluated both by an instrument of assessing stroke impact upon general health and an instrument for assessing the everyday activities. PMID- 26361063 TI - Effect of ivabradine on numbers needed to treat for the prevention of recurrent hospitalizations in heart failure patients. AB - BACKGROUND: Ivabradine, a specific heart rate lowering agent, was shown in the SHIFT study to reduce time to first hospitalization for worsening heart failure (HF) in chronic systolic HF patients and also to reduce recurrent/total hospitalizations over the study interval. We assessed the effects of adding ivabradine in patients with systolic HF on the number needed to treat (NNT) to reduce recurrent hospitalizations. METHODS: The SHIFT trial included 6505 patients with symptomatic HF (NYHA II-IV), left ventricular ejection fraction <=35% and heart rate >=70 bpm in sinus rhythm. Patients were randomized to either ivabradine or placebo in addition to guidelines-based drug therapy. The times to first hospitalization were analyzed using a univariate Cox proportional-hazards model; the associated NNT was calculated using Kaplan-Meier estimates of the time to-event curves at 1 year in each treatment arm. Recurrent hospitalizations were analyzed using a negative binomial and the estimated annual event rates used to calculate the associated patient-time NNTs respectively. RESULTS: The estimated NNT (number needed to initiate treatment with ivabradine to prevent one first HF hospitalization within 1 year) was 27 (estimated hazard ratio: 0.75, P < 0.0001). For recurrent HF hospitalizations, one event would be prevented on average per 14 patient-years for any year of follow-up over the course of SHIFT (estimated rate ratio: 0.71, P < 0.0001). A key limitation of this analysis is that it did not account for a relationship between recurrent HF hospitalizations and subsequent mortality. CONCLUSION: In chronic systolic HF the effect of ivabradine on reducing recurrent HF hospitalizations results in a lower NNT compared to the effect on the time for first hospitalization. The effect of ivabradine on recurrent hospitalizations, in addition to first events, may be a more appropriate measure when considering the impact of a treatment with ivabradine on healthcare resource utilization. PMID- 26361064 TI - (18)F-fluoromisonidazole PET reveals spatial and temporal heterogeneity of hypoxia in mouse models of human non-small-cell lung cancer. AB - AIM: To noninvasively observe dynamic changes in tumor hypoxia in mouse models of human non-small-cell lung cancer (NSCLC) using (18)F-fluoromisonidazole PET. MATERIALS & METHODS: Nude mice with NSCLC H460 and A549 subcutaneous xenografts were coinjected intravenously with (18)F-fluoromisonidazole and the hypoxia marker pimonidazole, and observed by serial PET scans. After sacrifice, the tumor distribution of (18)F-fluoromisonidazole and pimonidazole was compared by digital autoradiography and microscopy, respectively. RESULTS: The NSCLC hypoxic microenvironment was spatially heterogeneous. Serial PET scans over 48 h revealed an apparent change in the intratumoral distribution of (18)F-fluoromisonidazole. CONCLUSION: The tumor hypoxic microenvironment is spatially and temporally heterogeneous, and hypoxic cancer cells have a shorter life span when growing in vivo. Therefore, the concept of hypoxic resistance and hypoxia-targeting therapy of macroscopic tumors should be revisited. PMID- 26361065 TI - Prescription drug advertising, disease knowledge, and older adults' optimistic bias about the future risk of Alzheimer's disease. AB - This study aims to broaden the scope of knowledge on the role of direct-to consumer prescription drug advertising (DTCA) in the construction of consumers' optimistic bias regarding health issues and their intentions for coping actions. Based on an online survey of U.S. adults aged 65 years or older (N = 622), this study revealed that (a) respondents were optimistically biased in estimating their future risk of Alzheimer's disease (AD); (b) exposure to DTCA for AD medicine related negatively to optimistic bias when respondents had a low level of knowledge about AD, while the relationship disappeared when knowledge was high; (c) optimistic bias was negatively associated with intentions to seek information about AD and professional help to discuss it; and (d) optimistic bias mediated the relationship between the DTCA exposure * AD knowledge interaction and information- and help-seeking intentions. Implications for the theory and practice of DTCA are discussed. PMID- 26361066 TI - Gender differences in mood stabilizer medications prescribed to Veterans with serious mental illness. AB - BACKGROUND: Mood stabilizer medications (MSMs) can induce significant weight gain and other metabolic side effects. Research suggests that women are more susceptible to psychotropic medication-induced metabolic side effects than men. We examined gender differences in the likelihood of receiving an MSM with a lower liability for weight gain using data from the U.S. Department of Veterans Affairs (VA) healthcare system. METHODS: We identified 3823 VA patients with a schizophrenia or bipolar disorder diagnosis who initiated treatment with a MSM between 10/2006 and 9/2011. We used multivariable logistic regression analysis to examine gender differences in the likelihood of incident prescription of MSMs with low versus medium/high metabolic risk, adjusting for fiscal year of prescribing and demographic, mental health, and physical health characteristics. RESULTS: Overall, 47% of women were prescribed a low metabolic risk MSM compared to 26% of men (p<0.0001). In multivariable analysis, women were 2.19 times as likely as men to be prescribed a low metabolic risk MSM (95% CI: 1.84-2.60, p<0.0001). Several demographic and clinical covariates were also independently related to prescribing of MSMs by level of metabolic risk. LIMITATIONS: This study used retrospective administrative data collected from a VA healthcare system database, which does not allow us to understand the context in which MSM treatment decisions were made. CONCLUSIONS: Prescribing choices for MSMs by VA mental health prescribers and female Veterans may reflect a growing awareness of the potential adverse health consequences of these treatments in women. PMID- 26361068 TI - A chemical method for stabilizing a new series of solid solution Pr1-xCexScO3 (0.0 <=x<= 1.0) systems. AB - A new series of Pr1-xCexScO3 (0.0 <=x<= 1.0) compounds was synthesized by a two step synthesis route, involving a combustion reaction followed by reduction while heating in a low partial pressure of O2, generated by a zirconium sponge that acts as an oxygen getter. For the first time, perovskite solid solution formation was observed in this series in the entire homogeneity range. These compounds were characterized using XRD, Raman spectroscopy and DRUV-visible spectroscopy. Rietveld refinement was carried out on the XRD data to determine unit cell parameters, bond lengths, bond angles along with the tilt angles for ScO6 octahedra. The analyses of the Raman shift were also in agreement with the XRD data. All compounds in this series showed a decreasing trend in the bandgap from 4.74 to 2.91 eV as a function of increasing Ce(3+) concentration. PMID- 26361067 TI - Association of human microRNAs miR-22 and miR-491 polymorphisms with panic disorder with or without agoraphobia in a Korean population. AB - BACKGROUND: The possible involvement of microRNAs (miRNA) in psychiatric disorders has been recently recognized. Several miRNA polymorphisms have been found to be associated with panic disorder (PD) in European populations. However, the association of miRNA polymorphisms on PD has not been reported in Asian populations. We evaluated the effect of miR-22 and miR-491 polymorphisms on susceptibility to PD in a Korean population. METHODS: Genotyping for four polymorphic variants of the primary miRNA (pri-miRNA) regions of miR-22 (rs8076112 and rs6502892) and miR-491 (rs4977831 and rs2039391) was performed using blood samples of 341 Korean patients with PD and 229 healthy control subjects. To evaluate PD phenotypes, the Panic Disorder Severity Scale (PDSS) and Anxiety Sensitivity Inventory-Revised (ASI-R) were administered. RESULTS: Three single-nucleotide polymorphisms (SNPs) were found to be associated with PD: rs8076112 miR-22 and rs4977831 and miR-491 rs2039391. The rs8076112C/rs6502892C haplotypes of miR-22 and rs4977831G/rs2039391G and rs4977831A/rs2039391A haplotypes of miR-491 were significantly overrepresented in patients with PD than in healthy control subjects. In combination analysis, miR-22 rs8076112AC/rs6502892CC and rs8076112CC/rs6502892CC and miR-491 rs4977831AG/rs2039391AA were more frequent in patients with PD. Among the phenotype assessments, ASI-R scores were significantly associated with miR-22 rs6502892 in the subgroup with the agoraphobic phenotype. LIMITATIONS: The results should be considered preliminary due to the relatively small sample size and the selection of only four SNPs. CONCLUSIONS: This is the first report to show possible associations of miR-22 and miR-491 with genetic susceptibility to PD in a Korean population. PMID- 26361070 TI - Epigenetics and the Law: Introduction to this Issue. PMID- 26361069 TI - Effects of exenatide therapy on insulin resistance in the skeletal muscles of high-fat diet and low-dose streptozotocin-induced diabetic rats. AB - PURPOSE: The glucagon-like peptide (GLP)-1 agonist exenatide shows the same multiple effects on glucose homeostasis as native GLP-1, which can reduce blood glucose levels in individuals with type-2 diabetes mellitus (T2DM). However, its underlying action mechanism on glucose metabolism in the skeletal muscle of T2DM cases is unknown. We investigated the effects and action mechanisms of exenatide on insulin resistance (IR) in the skeletal muscle of high-fat diet and low-dose streptozotocin-induced T2DM rats. METHODS: Four groups of Sprague-Dawley rats were studied: non-T2DM (control, C); non-T2DM + exenatide (C + E); T2DM (D); and T2DM + exenatide (D + E). After eight weeks, isotope-tracer methodology was applied to measure the total rate of appearance (Ra) of glucose and glucose infusion rate (GIR) using a hyperinsulinemic-euglycemic clamp with 3-(3)H-glucose infusion. Glucose uptake in gastrocnemius muscles was determined by measuring 2 deoxy-D-(14)C-glucose radioactivity. Simultaneously, ultrastructural changes in the cells of gastrocnemius muscles were studied. RESULTS: In the D + E group, body weight and levels of fasting plasma glucose, triglyceride, total cholesterol, low-density lipoprotein and insulin were decreased significantly (p < 0.01) compared with the D group. The Ra of glucose (94.70 +/- 13.46 versus 121.07 +/- 16.55 MUmol/kg/min) was decreased (p < 0.01), whereas the exogenous GIR (144.68 +/- 11.03 versus 114.50 +/- 9.40 MUmol/kg/min) and glucose uptake in muscle (0.24 +/- 0.02 versus 0.17 +/- 0.02 MUmol/g/min) were increased markedly (p < 0.01). Ultrastructural observations revealed that exenatide attenuated the effect of swollen mitochondrial and endoplasmic reticulum within the cells of the skeletal muscle of T2DM rats. CONCLUSIONS: These data suggest that exenatide can significantly improve insulin sensitivity in skeletal muscle by increasing glucose uptake in T2DM rats. PMID- 26361071 TI - Effect of breastfeeding promotion interventions on child growth: a systematic review and meta-analysis. AB - AIM: To update a previous systematic review and meta-analyses about the effect of breastfeeding promotion interventions on child growth. METHODS: Studies evaluating the effect of any type of breastfeeding promotion intervention on child weight, length (or height) and weight/height (or BMI) were screened. Papers published between 2006 and 2014 were checked using the following databases: PubMed/MEDLINE, Embase, Cochrane Database of Systematic Reviews, Lilacs and SciELO. RESULTS: Sixteen studies were added to 19 other studies identified in the previous review, resulting in 35 studies. Meta-analyses of studies reporting on mean weight, length, weight/length or BMI showed that the interventions had no impact on weight or length/height z scores [pooled effect: 0.03 (95% confidence interval: -0.06;0.12) and 0.03 (95% confidence interval: -0.02;0.08), respectively] and had a modest, but significant, reduction in body mass index/weight-for-height z scores [z score mean difference: -0.06 (95% confidence interval: -0.12;0.00)], which was limited to studies from low- and high-incomes settings. For all three outcomes, there was important heterogeneity among studies, which should be taken into account when interpreting the results. CONCLUSION: Breastfeeding promotion interventions were not associated with significant changes in weight or length, but led to a modest, albeit significant, reduction in body mass index/weight-for-height z scores. PMID- 26361072 TI - Human neutrophil antigen-3a antibodies induce neutrophil stiffening and conformational activation of CD11b without shedding of L-selectin. AB - BACKGROUND: HNA-3a antibodies induce severe transfusion-related acute lung injury (TRALI) in which neutrophils play a major role. As neutrophil passage through the pulmonary microvasculature is a critical step in the pathogenesis of TRALI, we investigated the impact of HNA-3a antibodies on two important factors that could impair granulocyte passage through lung capillaries: the elasticity of neutrophils and the expression and activation of adhesion molecules. STUDY DESIGN AND METHODS: The impact of HNA-3a antibodies on the elasticity of neutrophils was investigated using atomic force microscopy (AFM). Neutrophils were settled on poly-2-hydroxyethyl-methacrylate-coated glass slides before treatment with anti HNA-3a plasma samples, control plasma, or control plasma containing formyl methionyl-leucyl-phenylalanine (fMLP). Elasticity measurements were carried out in a temperature-controlled perfusion chamber using an atomic force microscopy (AFM) device. The impact of HNA-3a antibodies on the surface expression of total CD11b, activation of CD11b, and L-selectin (CD62L) shedding was investigated by flow cytometry. The functional impact of HNA-3a antibodies on neutrophil adhesion was assessed using fibrinogen-coated plates. RESULTS: HNA-3a antibodies induced stiffening of neutrophils (+24%-40%; p < 0.05) to a similar extent as fMLP. This effect was blocked by treatment of neutrophils with cytochalasin D. While total surface expression of CD11b and L-selectin on neutrophils was largely unaffected, HNA-3a antibodies induced alloantigen-specific activation of CD11b (+72%-107%; p < 0.05) and increased adhesion of neutrophils to fibrinogen. CONCLUSION: Accumulation of neutrophils in the pulmonary microvasculature during severe TRALI is likely mediated by increased rigidity and CD11b-mediated adhesion of neutrophils leading to retention of neutrophils. PMID- 26361073 TI - Emerging immune checkpoints for cancer therapy. AB - BACKGROUND: Immunotherapy with immune checkpoint inhibitors has emerged as promising treatment modality for cancer based on the success of anti-CTLA-4 and PD-1/PD-L1 antibodies. LAG-3 and TIM-3 are two new immune checkpoints. The aim of this work is to review the role and application of LAG-3 and TIM-3 for cancer immunotherapy. MATERIAL AND METHODS: Literatures were searched and collected in Medline/PubMed. RESULTS: LAG-3 is presented as a CD4 homolog type I transmembrane protein which binds MHC class II molecules. LAG-3 negatively regulates T cell proliferation, homeostasis and function. IMP321 is formed of an extracellular portion of human LAG-3 fused to the Fc fraction of human IgG1 and has shown increased T cell responses and tolerability in phase I studies on advanced renal cell cancer. When combined with paclitaxel, IMP321 has exerted immune enhancement and tumor inhibition with no significant IMP321-related adverse events. TIM-3 belongs to the TIM family and mainly negatively regulates Th1 immunity. The TIM 3/galectin-9 pathway contributes to the suppressive tumor microenvironment. TIM-3 overexpression is associated with poor prognosis in a variety of cancers. Both LAG-3 and TIM-3 are coexpressed with other immune checkpoints. The application of LAG-3 or TIM-3 does play an important role in anti-tumor responses, and maybe better when combing with anti-CTLA-4 and anti-PD-1/L1 antibodies. CONCLUSIONS: These two immune checkpoints play crucial roles in cancer development and may be used in future clinical practice of cancer therapy. PMID- 26361074 TI - Skeletal muscle fiber characteristics and oxidative capacity in hemiparetic stroke survivors. AB - INTRODUCTION: Skeletal muscle is changed after stroke, but conflicting data exist concerning muscle morphology and oxidative enzyme capacity. METHODS: In 36 chronic stroke patients bilateral rectus femoris muscle biopsies were analyzed, and fiber type proportions and cross-sectional areas were determined by ATPase histochemistry. Enzymatic concentrations of citrate synthase (CS) and 3 Hydroxyacyl-coenzymeA-dehydrogenase (HAD) were determined using freeze-dried muscle tissue. Findings were correlated with clinical outcomes. RESULTS: In the paretic muscles the mean fiber area was smaller (P = 0.0004), and a lower proportion of type 1 fibers (P = 0.0016) and a higher proportion of type 2X fibers (P = 0.0002) were observed. The paretic muscle had lower CS (P = 0.013) and HAD concentrations (P = 0.037). Mean fiber area correlated with muscle strength (r = 0.43; P = 0.041), and CS concentration correlated with aerobic capacity (r = 0.47; P = 0.01). CONCLUSIONS: In stroke survivors there is a phenotypic shift toward more fatigable muscle fibers with reduced oxidative enzymatic capacity that relates to clinical outcomes. PMID- 26361075 TI - Inhibition of elongin C promotes longevity and protein homeostasis via HIF-1 in C. elegans. AB - The transcription factor hypoxia-inducible factor 1 (HIF-1) is crucial for responses to low oxygen and promotes longevity in Caenorhabditis elegans. We previously performed a genomewide RNA interference screen and identified many genes that act as potential negative regulators of HIF-1. Here, we functionally characterized these genes and found several novel genes that affected lifespan. The worm ortholog of elongin C, elc-1, encodes a subunit of E3 ligase and transcription elongation factor. We found that knockdown of elc-1 prolonged lifespan and delayed paralysis caused by impaired protein homeostasis. We further showed that elc-1 RNA interference increased lifespan and protein homeostasis by upregulating HIF-1. The roles of elongin C and HIF-1 are well conserved in eukaryotes. Thus, our study may provide insights into the aging regulatory pathway consisting of elongin C and HIF-1 in complex metazoans. PMID- 26361077 TI - Older kidney transplant patients experience less antibody-mediated rejection: a retrospective study of patients with mild to moderate sensitization. AB - BACKGROUND: There is a paucity of data stratifying by age the incidence of antibody-mediated rejection (AMR) in kidney transplant patients. METHODS: We performed a retrospective study of all adult, renal transplant recipients at a single institution between December 12, 2009, and March 16, 2011. Mildly and moderately sensitized patients were defined as patients with positive donor specific antibody (DSA) and negative flow cross-match. RESULTS: One hundred and forty-six patients were determined to have mild to moderate pre-transplantation sensitization. Thirty percent of patients younger than 40 yr of age experienced AMR vs. 15% in the older group (p = 0.04). There was a disproportionate increase in DSA for younger patients at 12 months, particularly for antibodies to class II. Histologic presence of C4d deposition was independently associated with AMR on multivariate analysis. CONCLUSIONS: Following renal transplantation, moderately sensitized patients aged 40 yr old and older were less likely to develop AMR when compared with younger patients. PMID- 26361076 TI - Factors Associated with Non-typhoidal Salmonella Bacteremia versus Typhoidal Salmonella Bacteremia in Patients Presenting for Care in an Urban Diarrheal Disease Hospital in Bangladesh. AB - BACKGROUND: Non-typhoidal Salmonella (NTS) and Salmonella enterica serovar Typhi bacteremia are the causes of significant morbidity and mortality worldwide. There is a paucity of data regarding NTS bacteremia in South Asia, a region with a high incidence of typhoidal bacteremia. We sought to determine clinical predictors and outcomes associated with NTS bacteremia compared with typhoidal bacteremia. METHODOLOGY: We performed a retrospective age-matched case-control study of patients admitted to the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh, between February 2009 and March 2013. We compared demographic, clinical, microbiological, and outcome variables of NTS bacteremic patients with age-matched S. Typhi bacteremic patients, and a separate comparison of patients with NTS bacteremia and patients with NTS gastroenteritis. PRINCIPAL FINDINGS: Of 20 patients with NTS bacteremia, 5 died (25% case fatality), compared to none of 60 age-matched cases of S. Typhi bacteremia. In univariate analysis, we found that compared with S. Typhi bacteremia, cases of NTS bacteremia had more severe acute malnutrition (SAM) in children under five years of age, less often presented with a duration of fever >= 5 days, and were more likely to have co-morbidities on admission such as pneumonia and clinical signs of sepsis (p<0.05 in all cases). In multivariable logistic regression, SAM, clinical sepsis, and pneumonia were independent risk factors for NTS bacteremia compared with S. Typhi bacteremia (p<0.05 in all cases). Notably, we found marked differences in antibiotic susceptibilities, including NTS strains resistant to antibiotics commonly used for empiric therapy of patients suspected to have typhoid fever. CONCLUSIONS/SIGNIFICANCE: Diarrheal patients with NTS bacteremia more often presented with co-morbidities and had a higher case fatality rate compared to those with typhoidal bacteremia. Clinicians in regions where both typhoid and NTS bacteremia are prevalent need to be vigilant about the possibility of both entities, especially given notable differences in antibiotic susceptibility patterns. PMID- 26361078 TI - How should I regulate my emotions if I want to run faster? AB - The present study investigated the effects of emotion regulation strategies on self-reported emotions and 1600 m track running performance. In stage 1 of a three-stage study, participants (N = 15) reported emotional states associated with best, worst and ideal performance. Results indicated that a best and ideal emotional state for performance composed of feeling happy, calm, energetic and moderately anxious whereas the worst emotional state for performance composed of feeling downhearted, sluggish and highly anxious. In stage 2, emotion regulation interventions were developed using online material and supported by electronic feedback. One intervention motivated participants to increase the intensity of unpleasant emotions (e.g. feel more angry and anxious). A second intervention motivated participants to reduce the intensity of unpleasant emotions (e.g. feel less angry and anxious). In stage 3, using a repeated measures design, participants used each intervention before running a 1600 m time trial. Data were compared with a no treatment control condition. The intervention designed to increase the intensity of unpleasant emotions resulted in higher anxiety and lower calmness scores but no significant effects on 1600 m running time. The intervention designed to reduce the intensity of unpleasant emotions was associated with significantly slower times for the first 400 m. We suggest future research should investigate emotion regulation, emotion and performance using quasi-experimental methods with performance measures that are meaningful to participants. PMID- 26361079 TI - Mass spectrometric characterization of a prolyl hydroxylase inhibitor GSK1278863, its bishydroxylated metabolite, and its implementation into routine doping controls. AB - Drug candidates, which have the potential of enhancing athletic performance represent a risk of being misused in elite sport. Therefore, there is a need for early consideration by anti-doping authorities and implementation into sports drug testing programmes. The hypoxia-inducible factor (HIF) or prolyl hydroxylase inhibitor (PHI) GSK1278863 represents an advanced candidate of an emerging class of therapeutics that possess substantial potential for abuse in sport due to their capability to stimulate the biogenesis of erythrocytes and, consequently, the individual's oxygen transport capacity. A thorough characterization of such analytes by technologies predominantly used for doping control purposes and the subsequent implementation of the active drug and/or its main urinary metabolite(s) are vital for comprehensive, preventive, and efficient anti-doping work. In the present study, the HIF PHI drug candidate GSK1278863 (comprising a 6 hydroxypyrimidine-2,4-dione nucleus) and its bishydroxylated metabolite M2 (GSK2391220A) were studied regarding their mass spectrometric behaviour under electrospray ionization (ESI-MS/MS) conditions. Synthesized reference materials were used to elucidate dissociation pathways by means of quadrupole/time-of flight high resolution/high accuracy tandem mass spectrometry, and their detection from spiked urine and elimination study urine samples under routine doping control conditions was established using liquid chromatography electrospray ionization-tandem mass spectrometry with direct injection. Dissociation pathways to diagnostic product ions of GSK1278863 (e.g. m/z 291, 223, and 122) were proposed as substantiated by determined elemental compositions and MS(n) experiments as well as comparison to spectra of the bishydroxylated analogue M2. An analytical assay based on direct urine injection using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) was developed for the simultaneous determination of GSK1278863 in combination with its bishydroxylated metabolite M2. Validation parameters including limit of detection (0.5-1 ng/mL), linearity, specificity, ion suppression/enhancement (<10%), intra- and inter-day precision (6-22%) were determined, demonstrating the fitness-for purpose of the assay for doping control screening of urine samples for the presence of the drug candidate and its main metabolite and for expanding current anti-doping efforts to this new class of therapeutics. However, administration study urine sample analysis suggested the use of M2 rather than the intact drug due to extensive metabolic conversion. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26361080 TI - Efficacy of Ribbond and a fibre post on the fracture resistance of reattached maxillary central incisors with two fracture patterns: a comparative in vitro study. AB - AIM: To compare the fracture resistance of maxillary central incisor fragments having two different fracture patterns and re-attached using two different posts fibre post and Ribbond. MATERIALS AND METHODS: Sixty extracted human maxillary central incisors were randomly divided into two groups of thirty samples each. Group A consisted of samples with 'labio-palatal' fracture pattern and Group B with a 'palato-labial' fracture pattern. The crowns of all the samples were sectioned using safe-sided diamond discs. Following cleaning and shaping and sectional obturation, the samples were randomly subdivided into two subgroups of 15 samples each. Prefabricated fibre post (Reforpost, Angelus, Londrina, PR, Brazil) was placed in all samples of Subgroup I, and Ribbond (Ribbond Inc., Seattle, WA, USA) was placed in all samples of Subgroup II. The fragments were re attached, fracture resistance was tested using Instron Universal Testing Machine, and the failure modes were assessed using a stereomicroscope. RESULTS: Group A with a labio-palatal fracture pattern exhibited higher fracture resistance as compared to Group B (palato-labial) in both subgroups. The fibre post (Subgroup I) exhibited higher fracture resistance as compared to Ribbond (Subgroup II). The Ribbond group exhibited significantly more number of repairable failures as compared to fibre post group. CONCLUSION: The labio-palatal pattern of fracture is a favourable type of fracture on palatal load application. The fragments re attached using the fibre post (Reforpost) had a higher resistance to fracture. However, teeth restored with Ribbond posts exhibited 100% repairable failures upon load application. The fracture pattern had no influence on the failure modes. PMID- 26361081 TI - Autoimmune neutropenia of infancy: Data from the Italian neutropenia registry. PMID- 26361082 TI - Conformational Analysis, Thermal Rearrangement, and EI-MS Fragmentation Mechanism of (1(10)E,4E,6S,7R)-Germacradien-6-ol by (13)C-Labeling Experiments. AB - An uncharacterized terpene cyclase from Streptomyces pratensis was identified as (+)-(1(10)E,4E,6S,7R)-germacradien-6-ol synthase. The enzyme product exists as two interconvertible conformers, resulting in complex NMR spectra. For the complete assignment of NMR data, all fifteen ((13)C1)FPP isotopomers (FPP=farnesyl diphosphate) and ((13)C15)FPP were synthesized and enzymatically converted. The products were analyzed using various NMR techniques, including (13)C, (13)C COSY experiments. The ((13)C)FPP isotopomers were also used to investigate the thermal rearrangement and EI fragmentation of the enzyme product. PMID- 26361083 TI - Spinal Heme Oxygenase-1 (HO-1) Exerts Antinociceptive Effects Against Neuropathic Pain in a Mouse Model of L5 Spinal Nerve Ligation. AB - OBJECTIVE: Heme oxygenase-1 (HO-1) exerts protective effects against ischemia and inflammation in the central nervous system. However, its role in neuropathic pain is still unclear. This study was undertaken to explore the distribution and possible mechanism of HO-1 in a mouse model of peripheral nerve injury. DESIGN AND METHODS: The experiment was conducted using a mouse model of L5 spinal nerve ligation (SNL). Mice received repeated intraperitoneal injection of Carbon monoxide-releasing molecule-2 (CO-RM-2), HO-1 inducer cobalt protoporphyrin IX (CoPP) or single intraspinal injection of lentivirus (LV) over-expressing HO-1. The behavior analyses were conducted. The distribution and expression of HO-1 in the spinal cord were analyzed. RESULTS: HO-1 but not HO-2 was upregulated in spinal cord microglia cells after nerve injury, and the repeated intraperitoneal administration of CORM-2 (10 mg/kg/d) or CoPP (5 mg/kg/d) both significantly reduced the mechanical allodynia and thermal hyperalgesia induced by SNL (P < 0.01). Intraspinal injection of LV-HO-1 persistently suppresses SNL-induced neuropathic pain (P < 0.01 or P < 0.05), significantly induced the spinal HO-1 protein content (P < 0.01) and inhibited the microglia activation (P < 0.01) 7 days after SNL. CONCLUSION: HO-1 upregulation could elicit potent analgesic effects against neuropathic pain, which might partly be attributed to inhibition of spinal microglia activation. HO-1 signaling pathway may present a novel strategy for the treatment of neuropathic pain. PMID- 26361084 TI - Detection of mutations in JAK2 exons 12-15 by Sanger sequencing. AB - INTRODUCTION: The Janus kinase (JAK)2 p.V617F gain-of-function mutation is a hallmark of BCR-ABL1-negative myeloproliferative neoplasms (MPNs). This study analyzed JAK2 mutations in 1811 patients tested between 2010 and 2013. METHODS: Exons 12-15 of JAK2 were sequenced in 1706 samples, and patients harboring mutations were clinically evaluated. RESULTS: Of 271 patients (16%) with JAK2 mutations, 148 (54.6%) were female and 123 (45.4%) were male; 103 (38%) were local and 168 (62%) were referred; and 13 (5%) had additional genetic abnormalities. The median patient age was 54 years, and there was only one pediatric patient. In agreement with previous reports, 262 patients (96.7%) were positive for the JAK2 p.V617F mutation. Non-p.V617F JAK2 mutations were detected in the remaining nine (3.3%) patients: five (1.8%) had a p.G571S mutation, and one (0.3%) each had p.E543_D544del, p.Y570Y silent, p.R541_E543delinsK, and p.I540_N542delinsM mutations. Diagnosis of 103 (38%) in-house cases revealed a predominance of MPN patients (87 cases, or 84.4%). CONCLUSION: JAK2 p.V617F was the most prevalent mutation detected among patients in this study. Non-p.V617F JAK2 mutations were identified in exons 12 and 13 corresponding to recently reported mutations, except for the novel p.I540_N542delinsM. PMID- 26361086 TI - Gas-Phase Partial Oxidation of Lignin to Carboxylic Acids over Vanadium Pyrophosphate and Aluminum-Vanadium-Molybdenum. AB - Lignin is a complex polymer that is a potential feedstock for aromatic compounds and carboxylic acids by cleaving the beta-O-4 and 5-5' linkages. In this work, a syringe pump atomizes an alkaline solution of lignin into a catalytic fluidized bed operating above 600 K. The vanadium heterogeneous catalysts convert all the lignin into carboxylic acids (up to 25 % selectivity), coke, carbon oxides, and hydrogen. Aluminum-vanadium-molybdenum mostly produced lactic acid (together with formic acid, acrylic acid, and maleic anhydride), whereas the vanadium pyrophosphate catalyst produced more maleic anhydride. PMID- 26361085 TI - Development of health-related quality of life and symptoms of anxiety and depression among persons diagnosed with cancer during adolescence: a 10-year follow-up study. AB - OBJECTIVE: The main aim was to investigate the development of health-related quality of life (HRQOL) and symptoms of anxiety and depression in a cohort diagnosed with cancer during adolescence from shortly after up to 10 years after diagnosis. METHODS: Participants (n = 61) completed the SF-36 and the HADS shortly; six, 12, and 18 months; and two, three, four, and 10 years (n = 28) after diagnosis. Polynomial change trajectories were used to model development. RESULTS: Polynomial change trajectories showed an initial increase which abated over time into a decrease which abated over time for the SF-36 subscales Mental Health and Vitality; an initial decline which abated over time into an increase for HADS anxiety; and an initial decline which abated over time into an increase which abated over time for HADS depression. The SF-36 mental component summary showed no change from two to 10 years after diagnosis whereas the SF-36 physical component summary showed an increase from two years after diagnosis which declined over time. Ten years after diagnosis 29% reported possible anxiety. CONCLUSIONS: Development of HRQOL and symptoms of anxiety and depression appears to be non-linear among persons diagnosed with cancer during adolescence. Well into permanent survivorship an increase in symptoms of anxiety is shown and approximately a third of the participants report possible anxiety. The findings indicate the need for: studies designed to pinpoint the times of highest psychological risk, clinical follow-up focusing on psychological problems, and development of effective psychological interventions for survivors of adolescent cancer. (c) 2015 The Authors. Psycho-Oncology published by John Wiley & Sons Ltd. PMID- 26361087 TI - One-pot synthesized hierarchical zeolite supported metal nanoparticles for highly efficient biomass conversion. AB - Hierarchically porous zeolite supported metal nanoparticles are successfully prepared through a base-assisted chemoselective interaction between the silicon species on the zeolite crystal surface and metal salts, in which in situ construction of mesopores and high dispersion of metal species are realized simultaneously. PMID- 26361088 TI - In vitro evaluation of peri-implantitis treatment modalities on Saos 2osteoblasts. AB - OBJECTIVES: Mechanical treatment of the implant surface through surgical approach is recommended to control peri-implantitis. Few conclusive data exist about the physical and chemical properties of treated titanium surfaces and their biocompatibility towards osteoblasts. This in vitro study aimed to evaluate four clinical procedures: plastic curette, air-abrasive device (Perio-Flow((r)) ), titanium brush (Ti-Brush((r)) ) and implantoplasty in terms of biocompatibility and osteogenic effect when cultured with Saos2. MATERIALS AND METHODS: Titanium disks were treated with plastic curette, air-abrasive device (Perio-Flow((r)) ), titanium brush (Ti-Brush((r)) ) and implantoplasty. Their surface microtopography (SEM), chemical composition (EDX) and wettability were evaluated. After seeding with Saos-2, cell morphology (1 h, 24 h), viability (three and 6 days) and alkaline phosphatase (ALP), osteoprotegerin (OPG) and osteocalcin (OCN) production (7 days) were analyzed. RESULTS: Control, plastic curette, Perio Flow((r)) and Ti-Brush((r)) groups presented complex microstructures including craters and micropits, whereas the implantoplasty group appeared much smoother (SEM). Titanium, oxygen, aluminium and carbon were identified as the main components in all disks with a decrease in the percentage of oxygen, carbon and an increase in the percentage of titanium in the implantoplasty group (EDX). Implantoplasty disks were also significantly more hydrophilic than the other ones, whose surfaces appeared hydrophobic. Saos-2 showed no morphological difference at 1 h. At 24 h, they appeared round shaped in all groups, except the implantoplasty group where the cells appeared stretched and elongated. Viability was similar in all groups, but significantly higher in the Perio-Flow((r)) than the control group at day six. ALP, OPG and OCN protein expression at 7 days was similar in all groups. CONCLUSIONS: Although implantoplasty was the only modality to modify the titanium surface morphology, composition and wettability, all treatment modalities promoted ALP, OPG and OCN production and appeared as valid approaches in terms of biocompatibility. PMID- 26361089 TI - Differential uptake of silver, copper and zinc suggests complementary species specific phytoextraction potential. AB - The aim of our study, conducted as a pot experiment, was to assess the potential of willow (Salix miyabeana), alfalfa (Medicago sativa), tall fescue (Festuca arundinacea), and Indian mustard (Brassica juncea) to remediate two brownfield soils differentially contaminated with Ag, Cu and Zn (up to 113.60, 47.50, and 117.00 mg kg(-1) respectively). While aboveground Ag accumulation was highest in B. juncea (4.60 +/- 2.58 mg kg(-1)), lower levels were also measured in M. sativa and F. arundinacea. Cu accumulation was observed in all species, but only in underground parts, and was highest in F. arundinacea (269.20 +/- 74.75 mg kg( 1)), with a bioconcentration factor of 13.85. Salix miyabeana was found to have the highest Zn aerial tissue concentration (119.96 +/- 20.04 mg kg(-1)). Because of its high Ag uptake, the remediation potential of B. juncea should be evaluated more extensively on the site from which we excavated the soil for this study. Given the multiple forms of contamination on the site and the differential specie related uptake evident in our findings, we hypothesize that an optimal plantation allowing expression of complementary remediation functions would include B. juncea for extraction of Ag, in combination with F. arundinacea for stabilization of Cu and S. miyabeana for extraction of Zn. PMID- 26361090 TI - Learning endoscopic resection in the esophagus. AB - BACKGROUND: Endoscopic resection is the cornerstone of endoscopic management of esophageal early neoplasia. However, endoscopic resection is a complex technique requiring knowledge and expertise. Our aims were to identify the most important learning points in performing endoscopic resection in a training setting and to provide information on how to improve endoscopic resection technique. METHODS: Six gastroenterologists at centers with multidisciplinary expertise in upper gastrointestinal oncology participated in a structured endoscopic resection training program, consisting of four training days with lectures and hands-on training on live pigs, further one-to-one hands-on training days, and written feedback (by an expert) on videos of unsupervised endoscopic resection procedures. The first 20 endoscopic resections of each participant were prospectively registered. Ninety learning points were independently identified by participants using a standardized questionnaire and by an expert providing written feedback on 33 unsupervised endoscopic resection videos. Three expert endoscopists selected and ranked the most important learning points in a consensus meeting. Results. The top 10 tips (illustrated by unique videos of three perforations) were: (1) allow time for inspection and use a high-definition endoscope; (2) create a preprocedural plan by placing electrocoagulation markings; (3) know the management of bleeding; (4) optimize the endoscopic view by repeatedly cleaning out stomach and target area; (5) use a therapeutic endoscope during resection; (6) always perform a test suction; (7) keep instruments close to the tip; (8) lift edges in piecemeal endoscopic cap resections; (9) know the management of perforation; (10) pin specimens down. CONCLUSIONS: This study summarized the most important learning points for performing endoscopic resection encountered during a structured endoscopic resection training program. PMID- 26361091 TI - Phylogenetic Relationships of Cucullanidae (Nematoda), with Observations on Seuratoidea and the Monophyly of Cucullanus, Dichelyne and Truttaedacnitis. AB - The phylogenetic relationships of Cucullanidae were explored using near-complete sequences of the 18S rDNA (rRNA gene). Sequences (1,750-1,760 bp) were obtained from 7 species of Cucullanidae belonging to 3 genera, Cucullanus (2 spp.), Dichelyne (2 spp.), Truttaedacnitis (3 spp.), and 1 species of Quimperiidae ( Paraseuratum sp.). These sequences were aligned with those of 128 other nematode species available in GenBank, including 3 other cucullanids (Dichelyne mexicanus, Cucullanus robustus, and Cucullanus baylisi) and 2 non-cucullanid seuratoids (Paraquimperia africana, and Linstowinema sp.). Bayesian (BPP) and maximum likelihood (ML) analyses of 2 different datasets strongly supported a monophyletic Cucullanidae. Bayesian analysis placed this family as the sister group to a clade containing species of Diplogasterida, Strongylida, Rhabditida, and Tylenchida with very strong support. Neither BPP nor ML analyses recovered a close relationship of Cucullanidae to Ascaridida. None of the 3 non-cucullanid seuratoid species were sister to Cucullanidae, nor did they form a monophyletic group of their own, which questions the monophyly of Seuratoidea and the relationships among species within this superfamily. The 3 genera of cucullanids were also not monophyletic, although morphologically similar species such as the 2 species of Cucullanus from Neotropical catfishes and 2 species of Dichelyne from Nearctic ictalurid catfishes were sister taxa with strong support. The results were ambiguous with respect to the relationship of 2 Truttaedacnitis spp. in Nearctic freshwater fishes but do not support Truttaedacnitis heterodonti, a parasite of heterodontid sharks, as belonging to this genus. The study shows that all aspects of the conventional classification of Seuratoidea and its taxa should be scrutinized by even more extensive sampling across hosts and habitats. PMID- 26361092 TI - Talking about fertility in the context of cancer: health care professional perspectives. AB - Health care professionals (HCPs) play a key role in providing information and counselling about the implications of cancer for fertility, however, many patients do not receive such information. The aim of this study was to examine the perspectives and practices of Australian HCPs in relation to discussing fertility with cancer patients. A mixed-methods design, comprising of an online survey of 263 HCPs [41.4% nurses; 25.5% doctors; 31% allied health care professionals (AHP)] and qualitative interviews with 49 HCPs, was utilised. HCPs reported that fertility is an important concern for patients and their partners; however, only 50% of doctors and nurses, and 24% of AHPs reported that they always addressed this issue. The primary barriers to discussing fertility were poor patient prognosis; patient gender or age; time constraints; and absence of appropriate resources and materials. Only a minority of HCPs (29%) had undergone training in discussing fertility with cancer patients. The majority wanted further training or education: including nurses (81.8%), AHPs (80.6%) and doctors (55.4%). HCPs agreed that a number of resources would assist them to raise fertility with their patients, including a list of appropriate referral sources, fact sheets, information booklets, a fertility consultation checklist and on-line resources. PMID- 26361093 TI - 2,2,2-Trifluoroethylation of Styrenes with Concomitant Introduction of a Hydroxyl Group from Molecular Oxygen by Photoredox Catalysis Activated by Visible Light. AB - The visible-light-induced photoredox difunctionalization reactions of styrenes with 1,1,1-trifluoro-2-iodoethane under an oxygen atmosphere in the presence of water give gamma-trifluoromethyl alcohols. In this radical reaction, the oxygen atom in the product originates from molecular oxygen, and water is shown to be important to promote the reaction. PMID- 26361094 TI - Rapid Copper Metallization of Textile Materials: a Controlled Two-Step Route to Achieve User-Defined Patterns under Ambient Conditions. AB - Throughout history earth-abundant copper has been incorporated into textiles and it still caters to various needs in modern society. In this paper, we present a two-step copper metallization strategy to realize sequentially nondiffusive copper(II) patterning and rapid copper deposition on various textile materials, including cotton, polyester, nylon, and their mixtures. A new, cost-effective formulation is designed to minimize the copper pattern migration on textiles and to achieve user-defined copper patterns. The metallized copper is found to be very adhesive and stable against washing and oxidation. Furthermore, the copper metallized textile exhibits excellent electrical conductivity that is ~3 times better than that of stainless steel and also inhibits the growth of bacteria effectively. This new copper metallization approach holds great promise as a commercially viable method to metallize an insulating textile, opening up research avenues for wearable electronics and functional garments. PMID- 26361095 TI - N-terminal modifications contribute to flowering time and immune response regulations. AB - A variety of N-terminal co-translational modifications play crucial roles in many cellular processes across eukaryotic organisms. Recently, N-terminal acetylation has been proposed as a regulatory mechanism for the control of plant immunity. Analysis of an N-terminal acetyltransferase complex A (NatA) mutant, naa15-1, revealed that NatA controls the stability of immune receptor Suppressor of NPR1, Constitutive 1 (SNC1) in an antagonistic fashion with NatB. Here, we further report on an antagonistic regulation of flowering time by NatA and NatB, where naa15-1 plants exhibit late flowering, opposite of the early flowering phenotype previously observed in natB mutants. In addition, we provide evidence for the involvement of another N-terminal modification, N-myristoylation, in controlling pathogen-associated molecular pattern (PAMP) triggered immunity (PTI) through the characterization of N-myristoyltransferase 1 (NMT1) defective mutants, which express a low level of NMT1 protein. The mutant line lacks induced production of reactive oxygen species and MAP kinase phosphorylation in response to treatment with the known immune elicitor flg22. NMT1 deficient plants also exhibit increased susceptibility to Pst hrcC, a non-pathogenic Pseudomonas syringae tomato strain lacking a functional type-III secretion system. The potential for the NatA-NatB antagonistic relationship to exist outside of the regulation of SNC1 as well as the disclosing of NMT1s role in PTI further supports the significant contribution of N-terminal co-translational modifications in the regulation of biological processes in plants, and present interesting areas for further exploration. PMID- 26361096 TI - Factors Determining Surgical Approaches to Basilar Bifurcation Aneurysms and Its Surgical Outcomes. AB - BACKGROUND: The basilar bifurcation aneurysm (BBA) is still considered to be one of the most challenging aneurysms for micro- and endovascular surgery. Classic surgical approaches, such as subtemporal, lateral supraorbital (LSO), and modified presigmoid, are still reliable and effective. OBJECTIVE: To analyze the clinical and radiological factors that affect the selection of these classic surgical approaches and their outcomes. METHODS: A retrospective analysis was conducted on the clinical and radiological data from computed tomographic angiography of BBA that have been clipped in the Department of Neurosurgery of Helsinki University Central Hospital between 2004 and 2014. Statistical analyses were performed using parametric and nonparametric tests where values were considered significant below P = .05. RESULTS: One hundred four patients with BBA underwent surgical clipping in our department between 2004 and 2014. Eight patients were excluded from the study because of incomplete preoperative radiological evaluations, leaving 96 patients for further analysis. Multiple aneurysm clipping, mean basilar bifurcation angle, and aneurysm neck distance from posterior clinoid process were shown to be factors that determine the surgical approach. Unfavorable outcome is strongly associated with poor Hunt-Hess grade on admission, distance from aneurysm neck (the posterior clinoid process), thrombosis, and dome size. CONCLUSION: Microsurgery for BBA clipping can be performed safely with simple surgical approaches: subtemporal and LSO. There are several factors determining the approach selected. Poor patient outcome in BBA was highly associated with poor preoperative clinical grade and large size of aneurysm dome. PMID- 26361097 TI - Impact of Disease Duration on Vascular Surrogates of Early Atherosclerosis in Childhood-Onset Systemic Lupus Erythematosus. AB - OBJECTIVE: To determine whether longer disease duration negatively impacts carotid intima-media thickness (CIMT), flow-mediated dilation (FMD), and pulse wave velocity (PWV) in a cohort of patients with childhood-onset systemic lupus erythematosus (SLE), and to compare CIMT, FMD, and PWV in patients with childhood onset SLE with those in healthy children and explore determinants of vascular test results in childhood-onset SLE. METHODS: Cross-sectional analysis was performed in a prospective longitudinal cohort of patients with childhood-onset SLE at the latest followup visit. Clinical and laboratory data were collected for patients with childhood-onset SLE. CIMT, FMD, and PWV were measured using standardized protocols in patients with childhood-onset SLE and healthy children. Correlations between disease duration and results of the 3 vascular tests were performed. Vascular data in patients with childhood-onset SLE were compared with those in healthy children. Multivariable linear regression was used to identify determinants of CIMT, FMD, and PWV in childhood-onset SLE. RESULTS: Patients with childhood-onset SLE (n = 149) and healthy controls (n = 178) were enrolled. The median age of the patients was 17.2 years (interquartile range [IQR] 15.7-17.9 years), and their median disease duration was 3.2 years (IQR 1.8-4.9 years). The median age of the healthy children was 14.7 years (IQR 13.1-15.9 years). Longer disease duration correlated with worse FMD (r = -0.2, P = 0.031) in patients with childhood-onset SLE. Patients with childhood-onset SLE had smaller (better) CIMT, higher (better) FMD, and similar PWV compared with healthy controls. Linear regression analysis explained <24% of the variation in vascular test results in patients with childhood-onset SLE, suggesting that other variables should be explored as important determinants of CIMT, FMD, and PWV. CONCLUSION: In this cohort of 149 patients with childhood-onset SLE, patients did not have worse CIMT, FMD, or PWV than did healthy controls. Longer disease duration was associated with worse FMD, suggesting progressive endothelial dysfunction over time. PMID- 26361098 TI - Emergency general surgery in a low-middle income health care setting: Determinants of outcomes. AB - INTRODUCTION: Emergency general surgery (EGS) has emerged as an important component of frontline operative care. Efforts in high-income settings have described its burden but have yet to consider low- and middle-income health care settings in which emergent conditions represent a high proportion of operative need. The objective of this study was to describe the disease spectrum of EGS conditions and associated factors among patients presenting in a low-middle income context. METHODS: March 2009-April 2014 discharge data from a university teaching hospital in South Asia were obtained for patients (>=16 years) with primary International Classification of Diseases, 9(th) revision, Clinical Modification diagnosis codes consistent with an EGS condition as defined by the American Association for the Surgery of Trauma. Outcomes included in-hospital mortality and occurrence of >=1 major complication(s). Multivariable analyses were performed, adjusting for differences in demographic and case-mix factors. RESULTS: A total of 13,893 discharge records corresponded to EGS conditions. Average age was 47.2 years (+/-16.8, standard deviation), with a male preponderance (59.9%). The majority presented with admitting diagnoses of biliary disease (20.2%), followed by soft-tissue disorders (15.7%), hernias (14.9%), and colorectal disease (14.3%). Rates of death and complications were 2.7% and 6.6%, respectively; increasing age was an independent predictor of both. Patients in need of resuscitation (n = 225) had the greatest rates of mortality (72.9%) and complications (94.2%). CONCLUSION: This study takes an important step toward quantifying outcomes and complications of EGS, providing one of the first assessments of EGS conditions using American Association for the Surgery of Trauma definitions in a low-middle income health care setting. Further efforts in varied settings are needed to promote representative benchmarking worldwide. PMID- 26361099 TI - A pilot study of eye-tracking devices in intensive care. AB - BACKGROUND: Eye-tracking devices have been suggested as a means of improving communication and psychosocial status among patients in the intensive care unit (ICU). This study was undertaken to explore the psychosocial impact and communication effects of eye-tracking devices in the ICU. METHODS: A convenience sample of patients in the medical ICU, surgical ICU, and neurosciences critical care unit were enrolled prospectively. Patients participated in 5 guided sessions of 45 minutes each with the eye-tracking computer. After completion of the sessions, the Psychosocial Impact of Assistive Devices Scale (PIADS) was used to evaluate the device from the patient's perspective. RESULTS: All patients who participated in the study were able to communicate basic needs to nursing staff and family. Delirium as assessed by the Confusion Assessment Method for the Intensive Care Unit was present in 4 patients at recruitment and none after training. The device's overall psychosocial impact ranged from neutral (-0.29) to strongly positive (2.76). Compared with the absence of intervention (0 = no change), patients exposed to eye-tracking computers demonstrated a positive mean overall impact score (PIADS = 1.30; P = .004). This finding was present in mean scores for each PIADS domain: competence = 1.26, adaptability = 1.60, and self esteem = 1.02 (all P < .01). CONCLUSION: There is a population of patients in the ICU whose psychosocial status, delirium, and communication ability may be enhanced by eye-tracking devices. These 3 outcomes are intertwined with ICU patient outcomes and indirectly suggest that eye-tracking devices might improve outcomes. A more in-depth exploration of the population to be targeted, the device's limitations, and the benefits of eye-tracking devices in the ICU is warranted. PMID- 26361100 TI - Naming names. PMID- 26361101 TI - Clinical guidance: Guidance on guidance. PMID- 26361102 TI - In practice: Bad posture. PMID- 26361103 TI - Orthodontics: A traumatic cause of ranula. PMID- 26361105 TI - Clinical: An opening. PMID- 26361106 TI - Feature: The IOC: past, present and future. PMID- 26361109 TI - Survey finds patients present 'challenging interactions' all too frequently. PMID- 26361111 TI - Dentists should not fear covert recordings. PMID- 26361112 TI - Perhaps they were Spock's? PMID- 26361116 TI - New cancer therapies and jaw necrosis. AB - Osteonecrosis of the jaw (ONJ) has a number of causes, the most familiar being radiation or bisphosphonate induced. Various other novel anti-neoplastic and bone targeting therapies that can also cause jaw necrosis have recently become available. This has led to the suggested acronym MRONJ for medication-related osteonecrosis of the jaw. This article summarises the available information on these drugs and their implications for the dental surgeon. PMID- 26361117 TI - Mouth sticks: their past, present and future. AB - Patients with physical disabilities precluding functional use of their limbs can benefit enormously from the expertise of the dental profession. The dental clinician is able to not only meet the routine oral health needs of these patients, but possesses the unique skills and knowledge to provide specialised oral prosthetic appliances which can facilitate a range of independent activities. Mouth sticks, as they are commonly known, are dental prostheses that are held intra-orally by the patient and manipulated to perform numerous actions such as drawing, writing and painting. They have been well documented within dental and occupational therapy literature and reports of their fabrication date back over 150 years, albeit in a very rudimentary form. The enduring value of mouth sticks to the physically disabled population is that they can provide a degree of self-reliance which would otherwise not be afforded to them. This article discusses the evolution of mouth sticks, principles of mouth stick design, patient selection criteria and treatment planning considerations. We present two recent clinical cases where mouth sticks have been indicated and have been indispensable to the user, detailing the clinical and laboratory stages involved. PMID- 26361121 TI - Primary care dentists' experience of treating avulsed permanent teeth. PMID- 26361122 TI - A retrospective analysis of the GDC's performance against its newly-approved fitness to practise guidance. PMID- 26361123 TI - Informed consent in primary dental care: patients' understanding and satisfaction with the consent process. AB - AIM: The purpose of the consent process is to give patients enough information to allow them to make an informed decision and preserve their autonomy. The patient's satisfaction and also their understanding of the consent process are audited only rarely and reports of such audits in dental practice are sparse. Reports from other specialties indicate that patients' understanding of the process is incomplete and often incorrect. We set about to perform such an audit to assess both our patients' satisfaction and their understanding of the consent process itself. DESIGN: A prospective questionnaire study of adults with capacity. SETTING: Primary care dental practice. DESIGN: A two-part questionnaire was designed, based on a questionnaire used for a similar purpose in paediatric surgery; the first part assessed the patient's opinion and satisfaction with the consent obtained by their dental professional and the second part assessed their understanding of the consent process in general and the legal issues around it. RESULTS: Part 1 - satisfaction with the consent process. Patients reported high level of satisfaction with the consent process at the practice (near 100% in major factors analysed). Part 2 - Understanding of the consent process. Significant misconceptions were identified: 60% thought that the form was for the protection of the dentist/hospital and 10-16% thought that by signing a consent form they relinquish their rights. A high level of patients' uncertainty (19-27%) was also evident for several of the questions. CONCLUSIONS: Although this study shows a very high level of patient satisfaction with the consent process at our dental practice, it also demonstrates very significant deficiencies in the patients' understanding of the consent process itself. This study corroborates the findings of other investigators in different medical disciplines and calls into question the adequacy of the current consent procedures as many patients are still unaware of the legal implications of consent; the majority of patients still do not recognise that the consent process should primarily be serving their interests by allowing them to express their autonomous choice pertaining to their treatment. Education will help reduce this discrepancy and promote a change from the past 'paternalistic' to the current 'informative, patient-centred' model of care. PMID- 26361124 TI - Updated posters to help manage medical emergencies in the dental practice. AB - Medical emergencies can occur in the dental practice. Medical Emergencies in the Dental Practice and Emergency Drugs in the Dental Practice posters have been designed to help dental practitioners to respond effectively and safely to a medical emergency. These posters, endorsed by the British Dental Association, are included with this issue of the British Dental Journal. Further copies can be downloaded from: https://www.walsallhealthcare.nhs.uk/medical-education.aspx. PMID- 26361125 TI - Establishing comprehensive oral assessments for children with safeguarding concerns. AB - The dental profession is well placed to contribute important information in child protection cases but no previous research has been reported that assesses the volume or impact of this information. Comprehensive oral assessment clinics were introduced and established as an integral part of comprehensive medical assessments for children with welfare concerns in Greater Glasgow and Clyde. An assessment protocol and standardised paperwork for comprehensive oral assessments were developed to enhance information sharing and patient access to appropriate care. Two cases are presented and discussed to demonstrate the value of dental input. PMID- 26361132 TI - Primary care dentists' experience of treating avulsed permanent teeth. AB - INTRODUCTION: An avulsed permanent tooth is one of the few true emergencies in dentistry. Children who suffer this injury require urgent dental care and prompt follow-up care. There is very limited evidence available regarding the provision of treatment for avulsion injuries in primary dental care. OBJECTIVES: To explore the experience of UK dentists in relation to the management of avulsed permanent teeth. METHOD: A self-completion questionnaire was designed and piloted. Questionnaires were sent to a random selection of one thousand GDPs with a stamped addressed return envelope. A second mailshot was sent to non-responders after eight weeks. Simple descriptive analysis was undertaken using Microsoft Excel. The results were compared with those from an earlier, similar study in Wales. RESULTS: A total response rate of 61% was achieved. Just over 40% of responding dentists recalled replanting an avulsed permanent tooth in a child. CONCLUSIONS: Many dentists have limited or no experience of treating children with avulsed permanent teeth. Thirty-four percent of dentists have children with avulsion injuries under their care. Children with these traumatic injuries may benefit from shared care involving an interdisciplinary specialist team, in line with recommendations from the British Society of Paediatric Dentistry National Clinical Guidelines for Management of Avulsed Permanent Teeth in Children. PMID- 26361133 TI - A retrospective analysis of the GDC's performance against its newly-approved fitness to practise guidance. AB - OBJECTIVES: To assess if the GDC considers relevant factors at all stages of its deliberations into misconduct, as required by the determinations in the cases of Cohen, Zygmunt, and Azzam; and to assess whether those circumstances described in the Indicative Sanctions Guidance as warranting erasure from GDC registers led to that outcome. DESIGN Retrospective analysis of practise committee transcripts. MATERIALS AND METHODS: The consideration of specific factors in determining impairment of fitness to practise was compared with their subsequent consideration when determining the severity of sanction. Additionally, cases that highlighted aggravating circumstances deemed as serious enough to warrant erasure were monitored. Pearson's Chi test was used to detect any variation from the expected distribution of data. RESULTS: Sixty-six cases met with the inclusion criteria. Of the five factors considered, all but one was more likely to be heard when determining sanction having first been factored in to the consideration of impairment. Additionally, there was a statistically significant correlation between the aggravating factors and erasure from the registers. CONCLUSIONS: The GDC do, in general, consider relevant factors at all stages of their deliberations into practitioner misconduct, and act in a manner that is consistent with their own guidance when determining sanction. PMID- 26361134 TI - Estimation of the in vitro eye irritating and inflammatory potential of lipopolysaccharide (LPS) and dust by using reconstituted human corneal epithelium tissue cultures. AB - CONTEXT: Eye irritation is a common complaint in indoor environment, but the causes have still not been identified among the multiple exposures in house environments. To identify the potential environmental factors responsible for eye irritation and study the possible mechanisms, an in vitro model for eye irritation is suggested. MATERIALS AND METHODS: In this study, reconstituted human corneal epithelium (HCE) tissue cultures were used to study the eye irritating and inflammatory potential of lipopolysaccharide (LPS) and dust. HCE tissue cultures were exposed to a range of concentrations of LPS for 6 h and dust for 24 h, respectively. After exposure, viability and secretion of interleukins (IL) IL-1beta, IL-8, and tumor necrosis factor (TNFalpha) were examined. Histology was used to indicate the morphological changes after dust exposure. RESULTS: Both LPS and dust affected HCE viability. There was an increased level of IL-8 after LPS exposure, while the concentrations of IL-1beta and TNFalpha remained unaffected. Dust exposure resulted in an elevation of both IL-1beta and IL-8, but not TNFalpha. Histology study showed increased vacuolization and reduced thickness after 24 h exposure to 5 mg/mL dust. DISCUSSION AND CONCLUSION: LPS and dust showed in vitro eye irritating and inflammatory potential, and cytokines/chemokines like IL-1beta and IL-8 may be involved in the mechanisms of eye irritation. The HCE tissue culture may be used as an in vitro model to study environmental exposure induced eye irritation and inflammation. PMID- 26361135 TI - Ultrasound guidance for upper and lower limb blocks. AB - BACKGROUND: Peripheral nerve blocks can be performed using ultrasound guidance. It is not yet clear whether this method of nerve location has benefits over other existing methods. This review was originally published in 2009 and was updated in 2014. OBJECTIVES: The objective of this review was to assess whether the use of ultrasound to guide peripheral nerve blockade has any advantages over other methods of peripheral nerve location. Specifically, we have asked whether the use of ultrasound guidance:1. improves success rates and effectiveness of regional anaesthetic blocks, by increasing the number of blocks that are assessed as adequate2. reduces the complications, such as cardiorespiratory arrest, pneumothorax or vascular puncture, associated with the performance of regional anaesthetic blocks SEARCH METHODS: In the 2014 update we searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 8); MEDLINE (July 2008 to August 2014); EMBASE (July 2008 to August 2014); ISI Web of Science (2008 to April 2013); CINAHL (July 2014); and LILACS (July 2008 to August 2014). We completed forward and backward citation and clinical trials register searches.The original search was to July 2008. We reran the search in May 2015. We have added 11 potential new studies of interest to the list of 'Studies awaiting classification' and will incorporate them into the formal review findings during future review updates. SELECTION CRITERIA: We included randomized controlled trials (RCTs) comparing ultrasound-guided peripheral nerve block of the upper and lower limbs, alone or combined, with at least one other method of nerve location. In the 2014 update, we excluded studies that had given general anaesthetic, spinal, epidural or other nerve blocks to all participants, as well as those measuring the minimum effective dose of anaesthetic drug. This resulted in the exclusion of five studies from the original review. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. We used standard Cochrane methodological procedures, including an assessment of risk of bias and degree of practitioner experience for all studies. MAIN RESULTS: We included 32 RCTs with 2844 adult participants. Twenty-six assessed upper-limb and six assessed lower-limb blocks. Seventeen compared ultrasound with peripheral nerve stimulation (PNS), and nine compared ultrasound combined with nerve stimulation (US + NS) against PNS alone. Two studies compared ultrasound with anatomical landmark technique, one with a transarterial approach, and three were three-arm designs that included US, US + PNS and PNS.There were variations in the quality of evidence, with a lack of detail in many of the studies to judge whether randomization, allocation concealment and blinding of outcome assessors was sufficient. It was not possible to blind practitioners and there was therefore a high risk of performance bias across all studies, leading us to downgrade the evidence for study limitations using GRADE. There was insufficient detail on the experience and expertise of practitioners and whether experience was equivalent between intervention and control.We performed meta-analysis for our main outcomes. We found that ultrasound guidance produces superior peripheral nerve block success rates, with more blocks being assessed as sufficient for surgery following sensory or motor testing (Mantel-Haenszel (M-H) odds ratio (OR), fixed-effect 2.94 (95% confidence interval (CI) 2.14 to 4.04); 1346 participants), and fewer blocks requiring supplementation or conversion to general anaesthetic (M-H OR, fixed-effect 0.28 (95% CI 0.20 to 0.39); 1807 participants) compared with the use of PNS, anatomical landmark techniques or a transarterial approach. We were not concerned by risks of indirectness, imprecision or inconsistency for these outcomes and used GRADE to assess these outcomes as being of moderate quality. Results were similarly advantageous for studies comparing US + PNS with NS alone for the above outcomes (M-H OR, fixed effect 3.33 (95% CI 2.13 to 5.20); 719 participants, and M-H OR, fixed-effect 0.34 (95% CI 0.21 to 0.56); 712 participants respectively). There were lower incidences of paraesthesia in both the ultrasound comparison groups (M-H OR, fixed-effect 0.42 (95% CI 0.23 to 0.76); 471 participants, and M-H OR, fixed effect 0.97 (95% CI 0.30 to 3.12); 178 participants respectively) and lower incidences of vascular puncture in both groups (M-H OR, fixed-effect 0.19 (95% CI 0.07 to 0.57); 387 participants, and M-H OR, fixed-effect 0.22 (95% CI 0.05 to 0.90); 143 participants). There were fewer studies for these outcomes and we therefore downgraded both for imprecision and paraesthesia for potential publication bias. This gave an overall GRADE assessment of very low and low for these two outcomes respectively. Our analysis showed that it took less time to perform nerve blocks in the ultrasound group (mean difference (MD), IV, fixed effect -1.06 (95% CI -1.41 to -0.72); 690 participants) but more time to perform the block when ultrasound was combined with a PNS technique (MD, IV, fixed-effect 0.76 (95% CI 0.55 to 0.98); 587 participants). With high levels of unexplained statistical heterogeneity, we graded this outcome as very low quality. We did not combine data for other outcomes as study results had been reported using differing scales or with a combination of mean and median data, but our interpretation of individual study data favoured ultrasound for a reduction in other minor complications and reduction in onset time of block and number of attempts to perform block. AUTHORS' CONCLUSIONS: There is evidence that peripheral nerve blocks performed by ultrasound guidance alone, or in combination with PNS, are superior in terms of improved sensory and motor block, reduced need for supplementation and fewer minor complications reported. Using ultrasound alone shortens performance time when compared with nerve stimulation, but when used in combination with PNS it increases performance time.We were unable to determine whether these findings reflect the use of ultrasound in experienced hands and it was beyond the scope of this review to consider the learning curve associated with peripheral nerve blocks by ultrasound technique compared with other methods. PMID- 26361136 TI - Reflections on Becoming an Older and More Experienced Psychotherapist. AB - In this article, I describe how greater self-awareness and increased affect tolerance changed my clinical work with patients. I provide a clinical example to illustrate how my personal growth occurred. Blind spots, created through both conflict and ignorance, are discussed. My acceptance of my limitations in general, as well as those that come with age, and the awareness of the limitations of time itself all increase as I age. Grief and mourning become more central in my work. My comfort and confidence increase, but awareness of my age makes me more selective about whom I will treat. I treasure the work more than ever and experience the benefits of mutual peer supervision increasing over time. I hope to convey what a privilege it has been to be a psychotherapist. PMID- 26361137 TI - Large gene overlaps and tRNA processing in the compact mitochondrial genome of the crustacean Armadillidium vulgare. AB - A faithful expression of the mitochondrial DNA is crucial for cell survival. Animal mitochondrial DNA (mtDNA) presents a highly compact gene organization. The typical 16.5 kbp animal mtDNA encodes 13 proteins, 2 rRNAs and 22 tRNAs. In the backyard pillbug Armadillidium vulgare, the rather small 13.9 kbp mtDNA encodes the same set of proteins and rRNAs as compared to animal kingdom mtDNA, but seems to harbor an incomplete set of tRNA genes. Here, we first confirm the expression of 13 tRNA genes in this mtDNA. Then we show the extensive repair of a truncated tRNA, the expression of tRNA involved in large gene overlaps and of tRNA genes partially or fully integrated within protein-coding genes in either direct or opposite orientation. Under selective pressure, overlaps between genes have been likely favored for strong genome size reduction. Our study underlines the existence of unknown biochemical mechanisms for the complete gene expression of A. vulgare mtDNA, and of co-evolutionary processes to keep overlapping genes functional in a compacted mitochondrial genome. PMID- 26361138 TI - Cardiac amyloidosis: pathology, nomenclature, and typing. AB - Amyloidosis is an increasingly recognized cause of heart disease, caused by the deposition of misfolded protein within the heart. These proteins may deposit systemically and include the heart or deposit only within the heart muscle itself. In either case, cardiac symptoms may be the primary manifestation. The diagnosis is usually made by the pathologist identifying amyloid within a tissue sample. The diagnosis, however, does not end with such visual recognition of the presence of amyloid. Newer generation pharmacotherapeutic agents that are protein specific necessitate a closer evaluation to determine the type of protein being deposited and accurately conveying this to the treating clinician. Herein, the gross and histopathologic features of cardiac amyloidosis are reviewed along with a review of amyloid typing strategies (both direct and indirect) that may be employed in the diagnostic workup as well as the nomenclature standards for reporting. PMID- 26361139 TI - MicroRNA-378 regulates neural stem cell proliferation and differentiation in vitro by modulating Tailless expression. AB - Previous studies have suggested that microRNAs (miRNAs) play an important role in regulating neural stem cell (NSC) proliferation and differentiation. However, the precise role of miRNAs in NSC remains largely unexplored. In this study, we showed that miR-378 can target Tailless (TLX), a critical regulator of NSC, to regulate NSC proliferation and differentiation. By bioinformatic algorithms, miR 378 was found to have a predicted target site in the 3'-untranslated region of TLX, which was verified by a dual-luciferase reporter assay. The expression of miR-378 was increased during NSC differentiation and inversely correlated with TLX expression. qPCR and Western blot analysis also showed that miR-378 negatively regulated TLX mRNA and protein expression in neural stem cells (NSCs). Intriguingly, overexpression of miR-378 increased NSC differentiation and reduced NSC proliferation, whereas suppression of miR-378 led to decreased NSC differentiation and increased NSC proliferation. Moreover, the downstream targets of TLX, including p21, PTEN and Wnt/beta-catenin were also found to be regulated by miR-378. Additionally, overexpression of TLX rescued the NSC proliferation deficiency induced by miR-378 overexpression and abolished miR-378-promoted NSC differentiation. Taken together, our data suggest that miR-378 is a novel miRNA that regulates NSC proliferation and differentiation via targeting TLX. Therefore, manipulating miR-378 in NSCs could be a novel strategy to develop novel interventions for the treatment of relevant neurological disorders. PMID- 26361140 TI - A phytoene desaturase homolog gene from the methanogenic archaeon Methanosarcina acetivorans is responsible for hydroxyarchaeol biosynthesis. AB - Hydroxyarchaeols are the typical core structures of archaeal membrane lipids uniquely produced by a limited number of methanogenic lineages, which are mainly classified in orders Methanosarcinales and Methanococcales. However, the biosynthetic machinery that is used for the biosynthesis of hydroxyarcheol core lipids has not been discovered. In this study, the ma0127 gene from Methanosarcina acetivorans, which encodes a phytoene desaturase-like protein, was found to be responsible for the hydration of a geranylgeranyl group in an archaeal-lipid precursor, sn-2,3-O-digeranylgeranylglyceryl phosphoglycerol, produced in Escherichia coli cells expressing several archaeal enzymes. LC-ESI tandem-MS analyses proved that hydration occurs at the 2',3'-double bond of the geranylgeranyl group, yielding a 3'-hydroxylated lipid precursor. This result suggests that the encoded protein MA0127 is a hydratase involved in hydroxyarchaeol biosynthesis, because M. acetivorans is known to produce hydroxyarchaeol core lipids with a 3'-hydroxyphytanyl group. Furthermore, the distribution of the putative orthologs of ma0127 among methanogens is generally in good agreement with that of hydroxyarchaeol producers, including anaerobic methanotrophs (ANMEs). PMID- 26361141 TI - Delocalized Claudin-1 promotes metastasis of human osteosarcoma cells. AB - Tight junction proteins (TJPs) including Claudins, Occludin and tight junction associated protein Zonula occludens-1 (ZO-1), are the most apical component of junctional complex that mediates cell-cell adhesion in epithelial and endothelial cells. In human malignancies, TJPs are often deregulated and affect cellular behaviors of tumor cells. In this study, we investigated alternations of TJPs and related biological characteristics in human osteosarcoma (OS). Claudin1 was increased in the metastatic OS cells (KRIB and KHOS) compared with the normal osteoblast cells (hFOB1.19) or primary tumor cells (HOS and U2OS), whereas no significant difference was found in Occludin and ZO-1. Immunohistochemistry, immunofluorescence and Western blotting revealed that Claudin1 was initially localized at cell junctions of normal osteoblasts, but substantially delocalized to the nucleus of metastatic OS cells. Phenotypically, inhibition of the nucleus Claudin1 expression compromised the metastatic potential of KRIB and KHOS cells. Moreover, we found that protein kinase C (PKC) but not PKA phosphorylation influenced Claudin1 expression and cellular functions, as PKC inhibitor (Go 6983 and Staurosporine) or genetic silencing of PKC reduced Claudin1 expression and decreased the motility of KRIB and KHOS cells. Taken together, our study implied that delocalization of claudin-1 induced by PKC phosphorylation contributes to metastatic capacity of OS cells. PMID- 26361142 TI - A prospective study of serum adiponectin and regression of metabolic syndrome: The ARIRANG study. AB - Increased serum adiponectin levels may play a protective role in metabolic syndrome. However, few prospective studies have examined the effect of serum adiponectin in the improvement of metabolic components in subjects with metabolic syndrome. We investigated the association of serum adiponectin levels with the regression of metabolic syndrome in a population-based longitudinal study. A total of 1308 adults (575 men and 733 women) with metabolic syndrome at baseline were examined and followed. Baseline serum adiponectin concentrations were measured by radioimmunoassay. During an average of 2.6 years of follow-up, metabolic syndrome had disappeared in 184 men (29.8%) and 235 women (32.1%). In multivariable adjusted models, the odds ratio (95% confidence interval) for regression of metabolic syndrome comparing the highest to the lowest quartiles of adiponectin levels was 0.93 (0.56-1.53) in men and 2.48 (1.54-4.01) in women. Increased serum adiponectin is a predictor for the regression of metabolic syndrome in women. Adiponectin may have potential therapeutic applications in metabolic disease. PMID- 26361143 TI - Expressions of multiple umami taste receptors in oral and gastrointestinal tissues, and umami taste synergism in chickens. AB - Umami taste is one of the five basic taste qualities, along with sweet, bitter, sour, and salty, and is elicited by some l-amino acids and their salts, including monopotassium l-glutamate (MPG). The unique characteristic of umami taste is that it is synergistically enhanced by 5'-ribonucleotides such as inosine 5' monophosphate (IMP). Unlike the other four basic taste qualities, the presence of umami taste sense in avian species is not fully understood. In this study, we demonstrated the expression of multiple umami taste receptor candidates in oral and gastrointestinal tract tissues in chickens using RT-PCR analysis. We first showed the metabotropic glutamate receptors (mGluRs) expressed in these tissues. Furthermore, we examined the preference for umami taste in chickens, focusing on the synergistic effect of umami taste as determined by the two-feed choice test. We concluded that chickens preferred feed containing both added MPG and added IMP over feeds containing either added MPG or added IMP alone and over the control feed. These results suggest that the umami taste sense and synergism are conserved in chickens. PMID- 26361144 TI - Endoplasmic reticulum stress activation mediates Ginseng Rg3-induced anti gallbladder cancer cell activity. AB - In the current study, we examined the potential effect of Ginsenoside Rg3 against gallbladder cancer cells, the underlying signaling mechanisms were also studied. We demonstrated that Rg3 exerted potent cytotoxic and pro-apoptotic activity against established and primary human gallbladder cancer cells. Yet it was safe to non-cancerous gallbladder epithelial cells. At the molecular level, we showed that Rg3 induced endoplasmic reticulum (ER) stress activation, the latter was evidenced by C/EBP homologous protein (CHOP) upregulation, inositol-requiring enzyme 1 (IRE1)/PKR-like endoplasmic reticulum kinase (PERK) phosphorylations, and caspase-12 activation in gallbladder cancer cells. Reversely, the ER stress inhibitor salubrinal, the caspase-12 inhibitor z-ATAD-fmk as well as CHOP shRNA knockdown significantly attenuated Rg3-induced cytotoxicity against gallbladder cancer cells. In vivo, we showed that Rg3 oral administration significantly inhibited GBC-SD gallbladder cancer xenograft growth in nude mice, its activity was, however, compromised with co-administration of the ER stress inhibitor salubrinal. Thus, we suggest that ER stress activation mediates Ginseng Rg3 induced anti-gallbladder cancer cell activity in vitro and in vivo. PMID- 26361145 TI - Effects of FoxO1 on podocyte injury in diabetic rats. AB - OBJECTIVE: This study was designed to investigate the protective effect of forkhead transcription factor O1 (FoxO1) on podocyte injury in rats with diabetic nephropathy. METHODS: Streptozotocin-induced diabetic rats were served as DM group, while DM rats transfected with blank lentiviral vectors (LV-pSC-GFP) or lentiviral vectors carrying constitutively active FoxO1 (LV-CA-FoxO1) were served as LV-NC group or LV-CA group, respectively. The control group (NG) consisted of uninduced rats that received an injection of diluent buffer. At 2, 4, and 8 weeks after transfection, the levels of urine albumin, blood glucose, blood urea nitrogen, serum creatinine and urine podocalyxin were measured. Real-time PCR and western blotting were performed to measure mRNA and protein levels of FoxO1, podocalyxin, nephrin, and desmin in renal cortex. In addition, light and electron microscopy were used to detect structural changes in the glomerulus and podocytes. RESULTS: Compared with the rats in LV-NC and DM groups, LV-CA rats showed a significant increase in FoxO1 mRNA and protein levels and a distinct decrease in urine albumin, blood urea nitrogen, and serum creatinine (except at the two-week time point) levels (p < 0.05). Podocalyxin and nephrin mRNA and protein levels increased (p < 0.05), whereas desmin mRNA and protein levels decreased (p < 0.05). Pathological changes in glomerulus were also ameliorated in LV-CA group. CONCLUSIONS: Upregulating expression of FoxO1 by transduction with recombinant lentivirus ameliorates podocyte injury in diabetic rats. PMID- 26361146 TI - The NLRP3 inflammasome is dispensable for ER stress-induced pancreatic beta-cell damage in Akita mice. AB - Uncontrolled endoplasmic reticulum (ER) stress activates members of the NOD-like receptor family, which are involved in the pyrin domain containing 3 (NLRP3) inflammasome pathway. This pathway has been proposed to contribute to beta-cell dysfunction and death. However, the connection between ER stress and NLRP3 inflammasome activation remains controversial. Here we generated Akita/KO (Ins2(+/C96Y); NLRP3(-/-)) mice by crossing Akita (Ins2(+/C96Y); NLRP3(+/+)) mice with NLRP3 KO (Ins2(+/+); NLRP3(-/-)) mice. We then compared the metabolic phenotypes of the different strains. Knockout of the NLRP3 inflammasome did not affect the onset or the severity of diabetes in Akita/KO mice at any point of the study. Histological observations of pancreatic islets supported these findings. Tunicamycin-exposed islets from NLRP3 KO mice exhibited similar levels of ER stress and apoptosis induction as islets from WT (Ins2(+/+); NLRP3(+/+)) mice. Furthermore, NLRP3 deletion did not prevent tunicamycin-mediated reduction of glucose-stimulated insulin secretion. In conclusion, deletion of the NLRP3 inflammasome did not protect against ER stress-induced diabetes development or beta-cell damage, indicating that beta cell death in Akita mice is not mediated via activation of the NLRP3 inflammasome. PMID- 26361147 TI - MicroRNA-203-mediated posttranscriptional deregulation of CPEB4 contributes to colorectal cancer progression. AB - Elevated cytoplasmic polyadenylation element-binding 4 (CPEB4) is aberrantly expressed in several malignant cancers. However, its expression pattern, clinical significance, and biological function in colorectal cancer are still unknown. In this study, we demonstrated that CPEB4 is abundantly overexpressed in colorectal cancers and has the potential to be used for predicting clinical outcomes of colorectal cancer patients. We suppressed CPEB4 expression by small interfering RNA (siRNA) in SW480 and LOVO cells to clarify the role of CPEB4 on the cell apoptosis and proliferation in vitro. Further study revealed that knockdown of CPEB4 decreased the expression of anti-apoptotic protein B-cell lymphoma-extra large (Bcl-XL), but enhanced the expression of B-cell lymphoma-2-associated X (Bax). In addition, we indicated that CPEB4 is a novel target of miR-203, a tumor suppressive microRNA. Notably, restoration of CPEB4 in SW480 cells inhibited miR 203-induced apoptosis signaling pathway, which in turn enhanced cell proliferation and suppressed cell apoptosis. Taken together, our findings imply that posttranscriptional deregulation of CPEB4 contributes to the inhibited cell proliferation and the enhanced cell apoptosis in colorectal cancer, and directly targeting CPEB4 by miR-203 might be a novel strategy in colorectal cancer treatment. PMID- 26361148 TI - Verteporfin without light stimulation inhibits YAP activation in trabecular meshwork cells: Implications for glaucoma treatment. AB - Verteporfin, a photosensitizer, is used in photodynamic therapy to treat age related macular degeneration. In a glaucoma mouse model, Verteporfin without light stimulation has been shown to reduce intraocular pressure (IOP) but the mechanism is unknown. Recent studies have shown that Verteporfin inhibits YAP without light stimulation in cancer cells. Additionally, YAP has emerged as an important molecule in the pathogenesis of glaucoma. We hypothesize that YAP inactivation by Verteporfin in trabecular meshwork (TM) may be related to the reduced IOP observed in vivo. As contractility of TM tissues is associated with IOP, collagen gel contraction assay was used to assess the effect of Verteporfin on contractility of TM cells. Human TM cells were embedded in collagen gel and treated with Verteporfin for 48 h. Areas of collagen gel sizes were quantified by ImageJ. To assess the effect of Verteporfin on the expression of YAP, human TM cells were treated with Verteporfin for 24 h and the expression of YAP was determined by Western blotting. To determine the cytotoxic effect of Verteporfin, human TM cells were treated with Verteporfin for 24 h, and then the cell viability was assessed by WST-1. We demonstrated here that Verteporfin (i) abolishes TM cell-mediated collagen gel contraction in a dose-dependent manner, (ii) attenuates expression of YAP and CTGF (connective tissue growth factor, a direct YAP target gene) in a dose-dependent manner, and (iii) has no significant cytotoxicity below 2 MUM. Taken together, Verteporfin may facilitate aqueous humor outflow through the conventional outflow system and reduce IOP by inactivating YAP. PMID- 26361149 TI - Stanniocalcin 2 promotes cell proliferation and cisplatin resistance in cervical cancer. AB - Cervical cancer is one of the most common carcinomas in the female reproductive system. Treatment of cervical cancer involves surgical removal and chemotherapy. Resistance to platinum-based chemotherapy drugs including cisplatin has increasingly become an important problem in the treatment of cervical cancer patients. We found in this study that stanniocalcin 2 (STC2) expression was upregulated in both cervical cancer tissues and cell lines. The levels of STC2 expression in cervical cancer cell lines were positively correlated with the rate of cell proliferation. Furthermore, in cisplatin resistant cervical cancer cells, the levels of STC2 expression were significantly elevated. Modulation of STC2 expression by siRNA or overexpression in cisplatin resistant cells resulted in altered cell survival, apoptosis, and cisplatin resistance. Finally, we found that there was significant difference in the activity of the MAPK signaling pathway between cisplatin sensitive and resistant cervical cancer cells, and that STC2 could regulate the activity of the MAPK signaling pathway. PMID- 26361150 TI - Revascularization in Patients With Multivessel Coronary Artery Disease and Chronic Kidney Disease: Everolimus-Eluting Stents Versus Coronary Artery Bypass Graft Surgery. AB - BACKGROUND: Randomized trials of percutaneous coronary intervention (PCI) versus coronary artery bypass graft (CABG) routinely exclude patients with chronic kidney disease (CKD). OBJECTIVES: This study evaluated outcomes of PCI versus CABG in patients with CKD. METHODS: Patients with CKD who underwent PCI using everolimus-eluting stents were propensity-score matched to patients who underwent isolated CABG for multivessel coronary disease in New York. The primary outcome was all-cause mortality. Secondary outcomes were myocardial infarction (MI), stroke, and repeat revascularization. RESULTS: Of 11,305 patients with CKD, 5,920 patients were propensity-score matched. In the short term, PCI was associated with a lower risk of death (hazard ratio [HR]: 0.55; 95% confidence interval [CI]: 0.35 to 0.87), stroke (HR: 0.22; 95% CI: 0.12 to 0.42), and repeat revascularization (HR: 0.48; 95% CI: 0.23 to 0.98) compared with CABG. In the longer term, PCI was associated with a similar risk of death (HR: 1.07; 95% CI: 0.92 to 1.24), higher risk of MI (HR: 1.76; 95% CI: 1.40 to 2.23), a lower risk of stroke (HR: 0.56; 95% CI: 0.41 to 0.76), and a higher risk of repeat revascularization (HR: 2.42; 95% CI: 2.05 to 2.85). In the subgroup with complete revascularization with PCI, the increased risk of MI was no longer statistically significant (HR: 1.18; 95% CI: 0.67 to 2.09). In the 243 matched pairs of patients with end-stage renal disease on hemodialysis, PCI was associated with significantly higher risk of death (HR: 2.02; 95% CI: 1.40 to 2.93) and repeat revascularization (HR: 2.44; 95% CI: 1.50 to 3.96) compared with CABG. CONCLUSIONS: In patients with CKD, CABG is associated with higher short-term risk of death, stroke, and repeat revascularization, whereas PCI with everolimus eluting stents is associated with a higher long-term risk of repeat revascularization and perhaps MI, with no long-term mortality difference. In the subgroup on dialysis, the results favored CABG over PCI. PMID- 26361151 TI - Everolimus-Eluting Coronary Stents for Patients With Chronic Kidney Disease: What Explains the Magic? PMID- 26361152 TI - Comparative Effectiveness of Angiotensin-Converting Enzyme Inhibitor-Based Treatment on Cardiovascular Outcomes in Hypertensive Blacks Versus Whites. AB - BACKGROUND: Clinical trial evidence suggests poorer outcomes in blacks compared with whites when treated with an angiotensin-converting enzyme (ACE) inhibitor based regimen, but this has not been evaluated in clinical practice. OBJECTIVES: This study evaluated the comparative effectiveness of an ACE inhibitor-based regimen on a composite outcome of all-cause mortality, stroke, and acute myocardial infarction (AMI) in hypertensive blacks compared with whites. METHODS: We conducted a retrospective cohort study of 434,646 patients in a municipal health care system. Four exposure groups (Black-ACE, Black-NoACE, White-ACE, White-NoACE) were created based on race and treatment exposure (ACE or NoACE). Risk of the composite outcome and its components was compared across treatment groups and race using weighted Cox proportional hazard models. RESULTS: Our analysis included 59,316 new users of ACE inhibitors, 47% of whom were black. Baseline characteristics were comparable for all groups after inverse probability weighting adjustment. For the composite outcome, the race treatment interaction was significant (p = 0.04); ACE use in blacks was associated with poorer cardiovascular outcomes (ACE vs. NoACE: 8.69% vs. 7.74%; p = 0.05) but not in whites (6.40% vs. 6.74%; p = 0.37). Similarly, the Black-ACE group had higher rates of AMI (0.46% vs. 0.26%; p = 0.04), stroke (2.43% vs. 1.93%; p = 0.05), and congestive heart failure (3.75% vs. 2.25%; p < 0.0001) than the Black-NoACE group. However, the Black-ACE group was no more likely to develop adverse effects than the White-ACE group. CONCLUSIONS: ACE inhibitor-based therapy was associated with poorer cardiovascular outcomes in hypertensive blacks but not in whites. These findings confirm clinical trial evidence that hypertensive blacks have poorer outcomes than whites when treated with an ACE inhibitor-based regimen. PMID- 26361153 TI - Using Practice-Based Evidence to Reduce Disparities in Care: A Virtuous Cycle Turns. PMID- 26361155 TI - How Does Elevated Lipoprotein(a) Cause Aortic Valve Stenosis? PMID- 26361154 TI - Oxidized Phospholipids, Lipoprotein(a), and Progression of Calcific Aortic Valve Stenosis. AB - BACKGROUND: Elevated lipoprotein(a) (Lp[a]) is associated with aortic stenosis (AS). Oxidized phospholipids (OxPL) are key mediators of calcification in valvular cells and are carried by Lp(a). OBJECTIVES: This study sought to determine whether Lp(a) and OxPL are associated with hemodynamic progression of AS and AS-related events. METHODS: OxPL on apolipoprotein B-100 (OxPL-apoB), which reflects the biological activity of Lp(a), and Lp(a) levels were measured in 220 patients with mild-to-moderate AS. The primary endpoint was the progression rate of AS, measured by the annualized increase in peak aortic jet velocity in m/s/year by Doppler echocardiography; the secondary endpoint was need for aortic valve replacement and cardiac death during 3.5 +/- 1.2 years of follow up. RESULTS: AS progression was faster in patients in the top tertiles of Lp(a) (peak aortic jet velocity: +0.26 +/- 0.26 vs. +0.17 +/- 0.21 m/s/year; p = 0.005) and OxPL-apoB (+0.26 +/- 0.26 m/s/year vs. +0.17 +/- 0.21 m/s/year; p = 0.01). After multivariable adjustment, elevated Lp(a) or OxPL-apoB levels remained independent predictors of faster AS progression. After adjustment for age, sex, and baseline AS severity, patients in the top tertile of Lp(a) or OxPL-apoB had increased risk of aortic valve replacement and cardiac death. CONCLUSIONS: Elevated Lp(a) and OxPL-apoB levels are associated with faster AS progression and need for aortic valve replacement. These findings support the hypothesis that Lp(a) mediates AS progression through its associated OxPL and provide a rationale for randomized trials of Lp(a)-lowering and OxPL-apoB-lowering therapies in AS. (Aortic Stenosis Progression Observation: Measuring Effects of Rosuvastatin [ASTRONOMER]; NCT00800800). PMID- 26361156 TI - Universal Screening for Familial Hypercholesterolemia in Children. AB - BACKGROUND: Individuals with familial hypercholesterolemia (FH) who are untreated have up to 100-fold elevated risk for cardiovascular complications compared with those who are unaffected. Data for identification of FH with a universal screening for hypercholesterolemia in children are lacking. OBJECTIVES: This study sought genetic identification of FH from a cohort of children with elevated serum total cholesterol (TC) concentration, detected in a national universal screening for hypercholesterolemia. METHODS: Slovenian children born between 1989 and 2009 (n = 272) with TC >6 mmol/l (231.7 mg/dl) or >5 mmol/l (193.1 mg/dl) plus a family history positive for premature cardiovascular complications, identified in a national universal screening for hypercholesterolemia at 5 years of age were genotyped for variants in LDLR, PCSK9, APOB, and APOE. RESULTS: Of the referred children, 57.0% carried disease-causing variants for FH: 38.6% in LDLR, 18.4% in APOB, and none in PCSK9. Nine novel disease-causing variants were identified, 8 in LDLR, and 1 in APOB. Of the remaining participants, 43.6% carried the APOE E4 isoform. Estimated detection rate of FH in the universal screening program from 2009 to 2013 was 53.6% (95% confidence interval [CI]: 34.5% to 72.8%), peaking in 2013 with an upper estimated detection rate of 96.3%. Variants in LDLR, APOB, or the APOE E4 isoform occurred in 48.6%, 60.0%, and 76.5%, respectively, of patients with a family history negative for cardiovascular complications. CONCLUSIONS: Most participants who were referred from a national database of universal screening results for hypercholesterolemia had genetically confirmed FH. Data for family history may not suffice for reliable identification of patients through selective and cascade screening. PMID- 26361157 TI - Lipid Screening in Children. PMID- 26361159 TI - Catastrophic Adverse Events During Cardiac Catheterization in Pediatric Pulmonary Hypertension May Not Be So Rare. PMID- 26361158 TI - Predictors of Catastrophic Adverse Outcomes in Children With Pulmonary Hypertension Undergoing Cardiac Catheterization: A Multi-Institutional Analysis From the Pediatric Health Information Systems Database. AB - BACKGROUND: Cardiac catheterization is the standard of care procedure for diagnosis, choice of therapy, and longitudinal follow-up of children and adults with pulmonary hypertension (PH). However, the procedure is invasive and has risks associated with both the procedure and recovery period. OBJECTIVES: The purpose of this study was to identify risk factors for catastrophic adverse outcomes in children with PH undergoing cardiac catheterization. METHODS: We studied children and young adults up to 21 years of age with PH undergoing 1 or more cardiac catheterization at centers participating in the Pediatric Health Information Systems database between 2007 and 2012. Using mixed-effects multivariable regression, we assessed the association between pre-specified subject- and procedure-level covariates and the risk of the composite outcome of death or initiation of mechanical circulatory support within 1 day of cardiac catheterization after adjustment for patient- and procedure-level factors. RESULTS: A total of 6,339 procedures performed on 4,401 patients with a diagnosis of PH from 38 of 43 centers contributing data to the Pediatric Health Information Systems database were included. The observed risk of composite outcome was 3.5%. In multivariate modeling, the adjusted risk of the composite outcome was 3.3%. Younger age at catheterization, cardiac operation in the same admission as the catheterization, pre-procedural systemic vasodilator infusion, and hemodialysis were independently associated with an increased risk of adverse outcomes. Pre procedural use of pulmonary vasodilators was associated with reduced risk of composite outcome. CONCLUSIONS: The risk of cardiac catheterization in children and young adults with PH is high relative to previously reported risk in other pediatric populations. The risk is influenced by patient-level factors. Further research is necessary to determine whether knowledge of these factors can be translated into practices that improve outcomes for children with PH. PMID- 26361160 TI - Long-Term Use of Cardiovascular Drugs: Challenges for Research and for Patient Care. AB - Little is known about the benefits and risks of the long-term use of cardiovascular drugs. Evidence from randomized clinical trials (RCTs) rarely goes beyond a few years of follow-up, but patients are often given continuous treatment with multiple drugs well into old age. We focus on 4 commonly used cardiovascular drug classes: aspirin, statins, beta-blockers, and angiotensin converting enzyme inhibitors given to patients after myocardial infarction. However, the issues raised apply more broadly to all long-term medications across cardiovascular diseases and the whole of medicine. The evidence and limitations of RCTs are addressed, as well as current practice in pre-licensing trials, the increasing problems of polypharmacy (especially in the elderly), the lack of trial evidence for withdrawal of drugs, the role of regulatory authorities and other stakeholders in this challenging situation, and the potential educational solutions for the medical profession. We conclude with a set of recommendations on how to improve the situation of long-term drug use. PMID- 26361162 TI - Using Appropriate Use Criteria to Address Pre-Authorization. PMID- 26361163 TI - The 3 "Rs"-Relax, Reflect, and Regroup: Avoiding Burnout During Cardiology Fellowship. PMID- 26361161 TI - What to Expect From the Evolving Field of Geriatric Cardiology. AB - The population of older adults is expanding rapidly, and aging predisposes to cardiovascular disease. The principle of patient-centered care must respond to the preponderance of cardiac disease that now occurs in combination with the complexities of old age. Geriatric cardiology melds cardiovascular perspectives with multimorbidity, polypharmacy, frailty, cognitive decline, and other clinical, social, financial, and psychological dimensions of aging. Although some assume that a cardiologist may instinctively cultivate some of these skills over the course of a career, we assert that the volume and complexity of older cardiovascular patients in contemporary practice warrants a more direct approach to achieve suitable training and a more reliable process of care. We present a rationale and vision for geriatric cardiology as a melding of primary cardiovascular and geriatrics skills, thereby infusing cardiology practice with expanded proficiencies in diagnosis, risks, care coordination, communications, end-of-life, and other competences required to best manage older cardiovascular patients. PMID- 26361164 TI - Low Operative Mortality Achieved With Surgical Septal Myectomy: Role of Dedicated Hypertrophic Cardiomyopathy Centers in the Management of Dynamic Subaortic Obstruction. PMID- 26361165 TI - Diastolic Pressure Gradient Predicts Outcome in Patients With Heart Failure and Preserved Ejection Fraction. PMID- 26361166 TI - Clinical Benefit of Warfarin in Dialysis Patients With Atrial Fibrillation. PMID- 26361167 TI - Reply: Clinical Benefit of Warfarin in Dialysis Patients With Atrial Fibrillation. PMID- 26361168 TI - Robot-Assisted Laparoscopic Partial Nephrectomy with the ALF-X Robot on Pig Models. PMID- 26361169 TI - Synopsis of the PI-RADS v2 Guidelines for Multiparametric Prostate Magnetic Resonance Imaging and Recommendations for Use. PMID- 26361170 TI - Reply from Authors re: Vincent Khoo. Is There Another Bite of the Cherry? The Case for Radical Local Therapy for Oligometastatic Disease in Prostate Cancer. Eur Urol 2016;69:13-4: Oligometastatic Prostate Cancer: More Than Just Cherry picking? PMID- 26361171 TI - A Systematic Review of the Inclusion (or Exclusion) of Women in HIV Research: From Clinical Studies of Antiretrovirals and Vaccines to Cure Strategies. AB - INTRODUCTION: The effect of clinical interventions can differ because of sex/gender. Studies have shown that women are often under-represented in medical research. The aim of this systematic literature review was to characterize women's participation in HIV clinical studies of antiretroviral drugs (ARV), prophylactic vaccines (VAX), and curative strategies (CURE). METHODS: Systematic PubMed searches were conducted to identify ARV, VAX, and CURE studies. Data were extracted on the number of women, date of publication, sources of funding, country of study, and trial phase. Correlates of female participation were assessed. RESULTS: Women represented a median of 19.2% participants in ARV studies (387), 38.1% in VAX studies (53), and 11.1% in CURE studies (104). Funding source was not correlated with the proportion of female participants in VAX and CURE studies but was for ARV studies (P = 0.03). ARV trials funded by private noncommercial sources had the highest proportion of women, whereas publicly funded trials had the lowest female participation (median 16.7%). The median proportion of women in ARV trials that were fully or partially funded by the National Institutes of Health was significantly lower than the median in trials funded by other sources (19.6% vs. 22.3%, P = 0.001). CONCLUSIONS: Although women comprise nearly half of people living with HIV, they continue to be under-represented in clinical studies. Despite federal policies that have been established to address this, our study shows that publicly funded ARV trials recruit even fewer women than other trials. There is an urgent need to ensure that HIV clinical studies consider sex/gender dimensions. PMID- 26361172 TI - Cost-Effectiveness of Frequent HIV Testing of High-Risk Populations in the United States. AB - PURPOSE: Data showing a high incidence of HIV infection among men who have sex with men (MSM) who had annual testing suggest that more frequent HIV testing may be warranted. Testing technology is also a consideration given the availability of sensitive testing modalities and the increased use of less-sensitive rapid, point-of-care antibody tests. We assessed the cost-effectiveness of HIV testing of MSM and injection drug users (IDUs) at 3- and 6-month intervals using fourth generation and rapid tests. METHODS: We used a published mathematical model of HIV transmission to evaluate testing intervals for each population using cohorts of 10,000 MSM and IDU. We incorporated HIV transmissions averted due to serostatus awareness and viral suppression. We included costs for HIV testing and treatment initiation, and also treatment costs saved from averted transmissions. RESULTS: For MSM, HIV testing was cost saving or cost effective over a 1-year period for both 6-month compared with annual testing and quarterly compared with 6-month testing using either test. Testing IDU every 6 months compared with annually was moderately cost effective over a 1-year period with a fourth generation test, while testing with rapid, point-of-care tests or quarterly was not cost effective. MSM results remained robust in sensitivity analysis, whereas IDU results were sensitive to changes in HIV incidence and continuum-of-care parameters. Threshold analyses on costs suggested that additional implementation costs could be incurred for more frequent testing for MSM while remaining cost effective. CONCLUSIONS: HIV testing of MSM as frequently as quarterly is cost effective compared with annual testing, but testing IDU more frequently than annually is generally not cost effective. PMID- 26361173 TI - Risk of HIV and Hepatitis B and C Over Time Among Men Who Inject Image and Performance Enhancing Drugs in England and Wales: Results From Cross-Sectional Prevalence Surveys, 1992-2013. AB - BACKGROUND: Infection risks among people who inject drugs (PWID) are widely recognized, but few studies have focused on image and performance enhancing drugs (IPEDs). Globally, concern about IPED injection has increased and, in the United Kingdom, IPED injectors have become the largest group using Needle and Syringe Programmes. Blood-borne virus prevalence trends among IPED injectors are explored. METHOD: Data from 2 surveys of IPED injectors (2010-2011; 2012-2013) and the national bio-behavioral surveillance system for PWID (1992-1997; 1998 2003; 2004-2009) were merged. Psychoactive drug injectors and women were excluded. Logistic regression analyses explored temporal changes. RESULTS: Between 1992 and 2009, median age increased from 25 to 29 years (N = 1296), years injecting from 2 to 4. There were 53 men who had sex with men (MSM). Overall, 0.93% had HIV, 4.4% ever had hepatitis B (HBV), and 3.9% hepatitis C (HCV, from 1998, N = 1083). In multivariable analyses, HIV increased in 2004-2009 [adjusted odds ratio (AOR) = 10 (95% confidence interval (CI): 0.94 to 106) vs. 1992-2003], and remained elevated (AOR = 4.12, 95% CI: 0.31 to 54, 2012-2013); HBV also increased in 2004-2009 (AOR = 3.98, 95% CI: 1.59 to 9.97). HCV prevalence increase was only borderline significant (AOR = 2.47, 95% CI: 0.90 to 6.77, 2010 2011). HIV and HBV were associated with MSM and HCV with sharing needles/syringes. Uptake of diagnostic testing for HIV and HCV, and HBV vaccination increased (to 43%, 32% and 44% respectively). Condom use was consistently poor; needle/syringe sharing occurred. CONCLUSION: Blood-borne virus prevalences among IPED injectors have increased and for HIV, is now similar to that among psychoactive drug injectors. Targeted interventions to reduce risks are indicated. PMID- 26361174 TI - Changing Antiretroviral Eligibility Criteria: Impact on the Number and Proportion of Adults Requiring Treatment in Swaziland. AB - OBJECTIVE: Early initiation of antiretroviral treatment (ART) at CD4 cell count >= 500 cells per microliter reduces morbidity and mortality in HIV-infected adults. We determined the proportion of HIV-infected people with high viral load (VL) for whom transmission prevention would be an additional benefit of early treatment. DESIGN: A randomly selected subset of a nationally representative sample of HIV-infected adults in Swaziland in 2012. METHODS: Eight to 12 months after a national survey to determine adult HIV prevalence, 1067 of 5802 individuals identified as HIV-infected were asked to participate in a follow-up cross-sectional assessment. CD4 cell enumeration, VL measurements, and ART status were obtained to estimate the proportion of currently untreated adults and of the entire HIV-infected population with high VL (>= 1000 copies/mL) whose treatment under a test-and-treat or VL threshold eligibility strategy would reduce HIV transmission. RESULTS: Of the 927 (87% of 1067) participants enrolled, 466 (50%) reported no ART use. Among them, 424 (91%) had VL >= 1000 copies per milliliter; of these, 148 (35%) were eligible for ART at the then existing CD4 count threshold of <350 cells per microliter; an additional 107 (25%) were eligible with expanded CD4 criterion of <500 cells per microliter; and 169 (40%) remained ART ineligible. Thus, 36% of the 466 currently untreated and 18% of the total 927 had high VL yet remained ART ineligible under a CD4 criterion of <500 cells per microliter. CONCLUSIONS: A test-and-treat or VL threshold for treatment eligibility is necessary to maximize the HIV transmission prevention benefits of ART. PMID- 26361175 TI - Distinct Compartmentalization in the CNS of SHIVKU-1-Infected Chinese Rhesus Macaque Is Associated With Severe Neuropathology. PMID- 26361176 TI - CD4/CD8 Ratio Predicts Yellow Fever Vaccine-Induced Antibody Titers in Virologically Suppressed HIV-Infected Patients. AB - BACKGROUND: Yellow fever vaccine (YFV) induces weaker immune responses in HIV infected individuals. However, little is known about YFV responses among antiretroviral-treated patients and potential immunological predictors of YFV response in this population. METHODS: We enrolled 34 antiretroviral therapy (ART) treated HIV-infected and 58 HIV-uninfected adults who received a single YFV dose to evaluate antibody levels and predictors of immunity, focusing on CD4(+) T-cell count, CD4(+)/CD8(+) ratio, and Human Pegivirus (GBV-C) viremia. Participants with other immunosuppressive conditions were excluded. RESULTS: Median time since YFV was nonsignificantly shorter in HIV-infected participants than in HIV uninfected participants (42 and 69 months, respectively, P = 0.16). Mean neutralizing antibody (NAb) titers was lower in HIV-infected participants than HIV-uninfected participants (3.3 vs. 3.6 log10mIU/mL, P = 0.044), a difference that remained significant after adjustment for age, sex, and time since vaccination (P = 0.024). In HIV-infected participants, lower NAb titers were associated with longer time since YFV (rho: -0.38, P = 0.027) and lower CD4(+)/CD8(+) ratio (rho: 0.42, P = 0.014), but not CD4(+) T-cell count (P = 0.52). None of these factors were associated with NAb titers in HIV-uninfected participant. GBV-C viremia was not associated with difference in NAb titers overall or among HIV-infected participants. CONCLUSIONS: ART-treated HIV-infected individuals seem to have impaired and/or less durable responses to YFV than HIV uninfected individuals, which were associated with lower CD4(+)/CD8(+) ratio, but not with CD4(+) T-cell count. These results supports the notion that low CD4(+)/CD8(+) ratio, a marker linked to persistent immune activation, is a better indicator of functional immune disturbance than CD4(+) T-cell count in patients with successful ART. PMID- 26361177 TI - Percutaneous treatment of an iatrogenic aorta-to-right atrium fistula. PMID- 26361179 TI - A level playing field. PMID- 26361178 TI - The clinical and cost burden of coronary calcification in a Medicare cohort: An economic model to address under-reporting and misclassification. AB - BACKGROUND: Coronary artery calcification (CAC) is a well-established risk factor for the occurrence of adverse ischemic events. However, the economic impact of the presence of CAC is unknown. OBJECTIVES: Through an economic model analysis, we sought to estimate the incremental impact of CAC on medical care costs and patient mortality for de novo percutaneous coronary intervention (PCI) patients in the 2012 cohort of the Medicare elderly (>=65) population. METHODS: This aggregate burden-of-illness study is incidence-based, focusing on cost and survival outcomes for an annual Medicare cohort based on the recently introduced ICD9 code for CAC. The cost analysis uses a one-year horizon, and the survival analysis considers lost life years and their economic value. RESULTS: For calendar year 2012, an estimated 200,945 index (de novo) PCI procedures were performed in this cohort. An estimated 16,000 Medicare beneficiaries (7.9%) were projected to have had severe CAC, generating an additional cost in the first year following their PCI of $3500, on average, or $56 million in total. In terms of mortality, the model projects that an additional 397 deaths would be attributable to severe CAC in 2012, resulting in 3770 lost life years, representing an estimated loss of about $377 million, when valuing lost life years at $100,000 each. CONCLUSIONS: These model-based CAC estimates, considering both moderate and severe CAC patients, suggest an annual burden of illness approaching $1.3 billion in this PCI cohort. The potential clinical and cost consequences of CAC warrant additional clinical and economic attention not only on PCI strategies for particular patients but also on reporting and coding to achieve better evidence based decision-making. PMID- 26361180 TI - Risk factors for postoperative delirium. PMID- 26361181 TI - Clinical risk prediction in schizophrenia. PMID- 26361182 TI - Maternal depression and child behavioural outcomes. PMID- 26361183 TI - Alternatives to psychiatric diagnosis. PMID- 26361184 TI - Diagnosis: one useful method among many. PMID- 26361185 TI - New treatment targets for autism spectrum disorders: EU-AIMS. PMID- 26361186 TI - Rethinking dose-response effects of cannabis use in adolescence. PMID- 26361187 TI - Rethinking dose-response effects of cannabis use in adolescence. PMID- 26361188 TI - Rethinking dose-response effects of cannabis use in adolescence - Authors' reply. PMID- 26361189 TI - Bipolar treatment efficacy. PMID- 26361190 TI - Bipolar treatment efficacy - Authors' reply. PMID- 26361192 TI - Addiction services in England: in need of an intervention. PMID- 26361194 TI - Graham Thornicroft. PMID- 26361193 TI - The horror, the horror: stigma on screen. PMID- 26361195 TI - Kate Bush: left to my imagination. PMID- 26361196 TI - Louder than war. PMID- 26361197 TI - One of these kids is not the same. PMID- 26361198 TI - Cognitive and brain reserve and the risk of postoperative delirium in older patients: analysis of data from a prospective observational study. AB - BACKGROUND: Cognitive and brain reserve theories suggest that aspects of neural architecture or cognitive processes modify the effect of neuropathological processes on cognitive outcomes. Although frequently studied in the context of dementia, reserve in delirium is understudied. METHODS: Using data from a prospective observational study, we examined the association of three markers of brain reserve (head circumference, MRI-derived brain volume, and leisure time physical activity), five markers of cognitive reserve (education, vocabulary, cognitive activities, cognitive demand of lifetime occupation, and interpersonal demand of lifetime occupation), and the risk of postoperative delirium in 566 older adults (age >=70 years) free of dementia undergoing scheduled surgery. FINDINGS: 135 (24%) of 566 patients developed delirium during the postoperative hospital stay. Of the reserve markers examined, only the Wechsler Test of Adult Reading was associated with the risk of delirium. A 0.5 SD better performance on the Wechsler Test of Adult Reading was associated with a 38% reduction in delirium risk (adjusted risk ratio of 0.62, 95% CI 0.45-0.85; p=0.01). INTERPRETATION: Most markers of reserve failed to predict delirium risk. The exception to this is the Wechsler Test of Adult Reading. Our findings suggest that the reserve markers that are important for delirium might be different from those thought to be important for dementia. FUNDING: National Institute on Aging, National Heart Lung and Blood Institute. PMID- 26361199 TI - Accumulated environmental risk determining age at schizophrenia onset: a deep phenotyping-based study. AB - BACKGROUND: Schizophrenia is caused by a combination of genetic and environmental factors, as first evidenced by twin studies. Extensive efforts have been made to identify the genetic roots of schizophrenia, including large genome-wide association studies, but these yielded very small effect sizes for individual markers. In this study, we aimed to assess the relative contribution of genome wide association study-derived genetic versus environmental risk factors to crucial determinants of schizophrenia severity: disease onset, disease severity, and socioeconomic measures. METHODS: In this parallel analysis, we studied 750 male patients from the Gottingen Research Association for Schizophrenia (GRAS) dataset (Germany) with schizophrenia for whom both genome-wide coverage of single nucleotide polymorphisms and deep clinical phenotyping data were available. Specifically, we investigated the potential effect of schizophrenia risk alleles as identified in the most recent large genome-wide association study versus the effects of environmental hazards (ie, perinatal brain insults, cannabis use, neurotrauma, psychotrauma, urbanicity, and migration), alone and upon accumulation, on age at disease onset, age at prodrome, symptom expression, and socioeconomic parameters. FINDINGS: In this study, we could show that frequent environmental factors become a major risk for early schizophrenia onset when accumulated (prodrome begins up to 9 years earlier; p=2.9*10(-10)). In particular, cannabis use-an avoidable environmental risk factor-is highly significantly associated with earlier age at prodrome (p=3.8*10(-20)). By contrast, polygenic genome-wide association study risk scores did not have any detectable effects on schizophrenia phenotypes. INTERPRETATION: These findings should be translated to preventive measures to reduce environmental risk factors, since age at onset of schizophrenia is a crucial determinant of an affected individual's fate and the total socioeconomic cost of the illness. FUNDING: German Research Foundation (Research Center for Nanoscale Microscopy and Molecular Physiology of the Brain), Max Planck Society, Max Planck Forderstiftung, EXTRABRAIN EU-FP7, ERA-NET NEURON. PMID- 26361200 TI - Postnatal depressive symptoms and child psychological development at 10 years: a prospective study of longitudinal data from the South African Birth to Twenty cohort. AB - BACKGROUND: In high-income countries, maternal postnatal depression is associated with adverse outcomes in the child. However, few studies have investigated this relation in countries of low and middle income. Furthermore, to our knowledge, no studies have followed up cohorts into later childhood. We aimed to investigate whether maternal depression 6 months after birth is associated with psychological difficulties in a socioeconomically disadvantaged South African cohort of children at age 10 years. METHODS: Birth to Twenty is a prospective, longitudinal, birth-cohort study based in the Soweto area of Johannesburg, South Africa. Mothers and children in this cohort have been followed up at timepoints ranging from before birth to age 10 years. Maternal mood was measured at 6 months with the Pitt depression inventory and at 10 years with the Centre for Epidemiologic Studies depression scale (CES-D). Child psychological functioning was assessed at 10 years with the South African child assessment schedule (SACAS). Our primary outcome was psychological development of children at age 10 years, measured by total score on the SACAS. Secondary outcomes were scores on externalising and internalising subscales of the SACAS. We used t tests to compare psychological outcomes between children whose mother had postnatal depression at 6 months and those whose mother did not have postnatal depression. We examined associations between maternal postnatal depression and child psychological outcomes by multivariate linear-regression analysis, adjusting for socioeconomic status and maternal depression at 10 years, and we used logistic regression to provide odds ratios for associations identified by linear regression. FINDINGS: 1866 mothers completed the Pitt depression inventory 6 months after the birth of their child; of these, 453 (24%) had symptoms of postnatal depression. At the 10-year assessment, 1012 mothers completed the CES-D questionnaire, of whom 747 (74%) were judged to have depression. Sociodemographic characteristics did not differ between mothers with and without depression at both 6 months and 10 years. After adjusting for socioeconomic status and maternal depression at 10 years, children whose mothers had postnatal depression at 6 months were more than twice as likely to have significant psychological difficulties 10 years later compared with children whose mothers did not have postnatal depression at 6 months (adjusted odds ratio 2.26, 95% CI 1.23-4.16). INTERPRETATION: Maternal postnatal depression is associated with adverse psychological outcomes in children up to 10 years later in countries of low and middle income. In view of the increased prevalence of postnatal depression in these settings, this finding has important implications for policy and interventions for children and their mothers. FUNDING: Wellcome Trust (UK), Medical Research Council of South Africa, Human Science Research Council (South Africa), University of the Witwatersrand. PMID- 26361201 TI - Early life adversity, genomic plasticity, and psychopathology. AB - Child maltreatment is associated with an increased risk of psychiatric disorders, and a range of health problems later in life. Research suggests that adverse events early in life can lead to changes in gene expression through epigenetic mechanisms that alter stress reactivity, brain function, and behaviour. Although epigenetic changes are often long lasting, they can be reversed with pharmacological and environmental manipulations. The complexity of the epigenome is not fully understood. The aim of this Review is to assess emerging data for the role of epigenetic mechanisms in stress-related psychiatric disorders with a focus on future research. We describe the epigenetic processes, key findings in this specialty, clinical implications of research, and methodological issues. Studies are needed to investigate new epigenetic processes other than methylation and assess the efficacy of interventions to reverse epigenetic processes associated with the effects of early life adversity. PMID- 26361202 TI - Mental health-related stigma in health care and mental health-care settings. AB - This Review considers the evidence for mental-health-related stigma in health care and mental-health-care settings. Do mental-health-care and other health-care professionals stigmatise people using their services? If so, what are the effects on quality of mental and physical health care? How can stigma and discrimination in the context of health care be reduced? We show that the contact mental-health care professionals have with people with mental illness is associated with positive attitudes about civil rights, but does not reduce stigma as does social contact such as with friends or family members with mental illness. Some evidence suggests educational interventions are effective in decreasing stigma especially for general health-care professionals with little or no formal mental health training. Intervention studies are needed to underpin policy; for instance, to decrease disparity in mortality associated with poor access to physical health care for people with mental illness compared with people without mental illness. PMID- 26361203 TI - Lithium and suicide. PMID- 26361204 TI - Aberrant sperm DNA methylation predicts male fertility status and embryo quality. AB - OBJECTIVE: To evaluate whether male fertility status and/or embryo quality during in vitro fertilization (IVF) therapy can be predicted based on genomewide sperm deoxyribonucleic acid (DNA) methylation patterns. DESIGN: Retrospective cohort study. SETTING: University-based fertility center. PATIENT(S): Participants were 127 men undergoing IVF treatment (where any major female factor cause of infertility had been ruled out), and 54 normozoospermic, fertile men. The IVF patients were stratified into 2 groups: patients who had generally good embryogenesis and a positive pregnancy (n = 55), and patients with generally poor embryogenesis (n = 72; 42 positive and 30 negative pregnancies) after IVF. INTERVENTION(S): Genomewide sperm DNA methylation analysis was performed to measure methylation at >485,000 sites across the genome. MAIN OUTCOME MEASURE(S): A comparison was made of DNA methylation patterns of IVF patients vs. normozoospermic, fertile men. RESULT(S): Predictive models proved to be highly accurate in classifying male fertility status (fertile or infertile), with 82% sensitivity, and 99% positive predictive value. Hierarchic clustering identified clusters enriched for IVF patient samples and for poor-quality-embryo samples. Models built to identify samples within these groups, from neat samples, achieved positive predictive value >= 94% while identifying >one fifth of all IVF patient and poor-quality-embryo samples in each case. Using density gradient prepared samples, the same approach recovered 46% of poor-quality-embryo samples with no false positives. CONCLUSION(S): Sperm DNA methylation patterns differ significantly and consistently for infertile vs. fertile, normozoospermic men. In addition, DNA methylation patterns may be predictive of embryo quality during IVF. PMID- 26361205 TI - Embryo selection versus natural selection: how do outcomes of comprehensive chromosome screening of blastocysts compare with the analysis of products of conception from early pregnancy loss (dilation and curettage) among an assisted reproductive technology population? AB - OBJECTIVE: To compare the incidence of numerical chromosomal abnormalities (NCAs) reported after preimplantation genetic screening (PGS) analysis compared with that reported after cytogenetic analysis of products of conception after spontaneous abortion. DESIGN: Retrospective study. SETTING: Private academic in vitro fertilization center. PATIENT(S): Cytogenetic reports of patients who underwent an IVF cycle with PGS of at least one biopsied embryo were compared with cytogenetic analysis reported from patients who had dilation and curettage (D&C) for the treatment of a spontaneous abortion after assisted reproductive technology (ART) treatment. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Frequencies for each numerical chromosomal abnormality from both groups were compared. RESULT(S): A total of 1,069 NCAs were reported after PGS (trisomy 54.3%, monosomy 45.7%, no polyploidies), resulting in a trisomy/monosomy ratio of 0.82. A total of 447 NCAs was reported after D&C (trisomy 83%, polyploidy 10.7%, monosomy 6.3%). The aneuploidies most frequently identified were similar in both groups and included 15, 16, 18, 21, and 22. Monosomies (n = 28, 6.3%) were rarely observed in the group that underwent D&C after ART. CONCLUSION(S): This review provides an analysis of the most commonly identified NCAs after PGS and in first trimester D&C samples in an infertile population utilizing ART. Although monosomies comprised >50% of all cytogenetic anomalies identified after PGS, there were very few identified in the post-D&C samples. This suggests that although monosomies occur frequently in the IVF population, they commonly do not implant. Despite this difference, this study demonstrated that the specific NCAs observed after PGS analysis and D&C were comparable. PMID- 26361206 TI - Effect of male body mass index on live-birth sex ratio of singletons after assisted reproduction technology. AB - OBJECTIVE: To determine the effect of male body mass index (BMI) on the probability of achieving a live birth and the sex ratio of singletons at birth after IVF and intracytoplasmic sperm injection (ICSI) treatment. DESIGN: A retrospective cohort study. SETTING: University-affiliated infertility center. PATIENT(S): Patients seeking infertility treatment who received IVF or ICSI treatment with autologous oocytes from January 2009 to December 2013. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Live-birth sex ratio of singletons at birth stratified by male BMI and adjusted by parental age, parental BMI, type of infertility, parity, embryo culture media, and cause of infertility. RESULT(S): A total of 8,490 couples undergoing IVF or ICSI treatment resulted in 39.12% live births and gave birth to 2,377 live birth singletons and 943 twins. There was no significant difference in the live birth rate between groups stratified by BMI. The probability of live births for overweight and obese groups were not decreased compared with the normal-weight group; similar null findings existed in the IVF and ICSI subgroups. Of note, the sex ratio of offspring in the overweight and obese male groups was significantly higher than in the normal weight group (1.27 vs. 1.07). Male BMI was significantly associated with sex ratio of singletons after adjusting for confounders. In twins, incidences of twins with male-male infants in the overweight/obese group were not different from the normal-weight group. CONCLUSION(S): Increased male BMI has no effect on live birth success, but has an increased probability of giving birth to male singletons. PMID- 26361207 TI - 450 IU versus 600 IU gonadotropin for controlled ovarian stimulation in poor responders: a randomized controlled trial. AB - OBJECTIVE: To compare the outcomes of controlled ovarian stimulation/in vitro fertilization cycles using 450 IU and 600 IU gonadotropin per day in women at risk of poor ovarian response. DESIGN: Prospective randomized controlled nonblinded study. SETTING: University-affiliated private IVF center. PATIENT(S): Women considered to be at risk of poor ovarian response: aged <41 years with basal FSH >10 IU/L, antimullerian hormone <1 ng/mL, antral follicle count <= 8, or a previous IVF cycle with >= 300 IU/d gonadotropin that resulted in a cancellation, <8 follicles, or <5 oocytes. INTERVENTION(S): A total of 356 patients underwent a microdose GnRH agonist flare-up IVF/intracytoplasmic sperm injection protocol with a fixed daily dose of either 450 IU FSH (n = 176) or 600 IU FSH (n = 180) equally divided between Menopur and Bravelle. MAIN OUTCOME MEASURE(S): Number of mature oocytes retrieved. RESULT(S): The two groups were similar in terms of age, ovarian reserve, cause of infertility, duration of stimulation, and cycle cancellation rate. There were no significant differences in the number of metaphase II oocytes retrieved (4 [range 0-6] vs. 4 [range 2 7]), fertilization rate (62.4% vs. 57.0%), biochemical pregnancy rate (20.5% vs. 22.9%), clinical pregnancy rate (16.4% vs. 18.3%), and implantation rate (29.8% vs. 30.4%) between the 450 IU and 600 IU groups, respectively. CONCLUSION(S): Gonadotropin of 600 IU/d does not improve outcome of IVF cycles compared with 450 IU/d in women at risk of poor ovarian response. CLINICAL TRIAL REGISTRATION NUMBER: NCT00971152. PMID- 26361208 TI - Histone H1: Lessons from Drosophila. AB - Eukaryotic genomes are structured in the form of chromatin with the help of a set of five small basic proteins, the histones. Four of them are highly conserved through evolution, form the basic unit of the chromatin, the nucleosome, and have been intensively studied and are well characterized. The fifth histone, histone H1, adds to this basic structure through its interaction at the entry/exit site of DNA in the nucleosome and makes an essential contribution to the higher order folding of the chromatin fiber. Histone H1 is the less conserved histone and the less known of them. Though for long time considered as a general repressor of gene expression, recent studies in Drosophila have rejected this view and have contributed to uncover important functions on genome stability and development. Here we present some of the most recent data obtained in the Drosophila model system and discuss how the lessons learnt in these studies compare and could be applied to all other eukaryotes. PMID- 26361209 TI - Ketamine-Induced Hallucinations. AB - BACKGROUND: Ketamine, the NMDA glutamate receptor antagonist drug, is increasingly employed as an experimental model of psychosis in healthy volunteers. At subanesthetic doses, it safely and reversibly causes delusion-like ideas, amotivation and perceptual disruptions reminiscent of the aberrant salience experiences that characterize first-episode psychosis. However, auditory verbal hallucinations, a hallmark symptom of schizophrenia, have not been reported consistently in healthy volunteers even at high doses of ketamine. SAMPLING AND METHODS: Here we present data from a set of healthy participants who received moderately dosed, placebo-controlled ketamine infusions in the reduced stimulation environment of the magnetic resonance imaging (MRI) scanner. We highlight the phenomenological experiences of 3 participants who experienced particularly vivid hallucinations. RESULTS: Participants in this series reported auditory verbal and musical hallucinations at a ketamine dose that does not induce auditory hallucination outside of the scanner. CONCLUSIONS: We interpret the observation of ketamine-induced auditory verbal hallucinations in the context of the reduced perceptual environment of the MRI scanner and offer an explanation grounded in predictive coding models of perception and psychosis - the brain fills in expected perceptual inputs, and it does so more in situations of altered perceptual input. The altered perceptual input of the MRI scanner creates a mismatch between top-down perceptual expectations and the heightened bottom-up signals induced by ketamine. Such circumstances induce aberrant percepts, including musical and auditory verbal hallucinations. We suggest that these circumstances might represent a useful experimental model of auditory verbal hallucinations and highlight the impact of ambient sensory stimuli on psychopathology. PMID- 26361210 TI - TLR9 Mediates Remote Liver Injury following Severe Renal Ischemia Reperfusion. AB - Ischemia reperfusion injury is a common cause of acute kidney injury and is characterized by tubular damage. Mitochondrial DNA is released upon severe tissue injury and can act as a damage-associated molecular pattern via the innate immune receptor TLR9. Here, we investigated the role of TLR9 in the context of moderate or severe renal ischemia reperfusion injury using wild-type C57BL/6 mice or TLR9KO mice. Moderate renal ischemia induced renal dysfunction but did not decrease animal well-being and was not regulated by TLR9. In contrast, severe renal ischemia decreased animal well-being and survival in wild-type mice after respectively one or five days of reperfusion. TLR9 deficiency improved animal well-being and survival. TLR9 deficiency did not reduce renal inflammation or tubular necrosis. Rather, severe renal ischemia induced hepatic injury as seen by increased plasma ALAT and ASAT levels and focal hepatic necrosis which was prevented by TLR9 deficiency and correlated with reduced circulating mitochondrial DNA levels and plasma LDH. We conclude that TLR9 does not mediate renal dysfunction following either moderate or severe renal ischemia. In contrast, our data indicates that TLR9 is an important mediator of hepatic injury secondary to ischemic acute kidney injury. PMID- 26361211 TI - Impacts of Mesopredator Control on Conservation of Mesopredators and Their Prey. AB - Declining large carnivore populations, increased habitat fragmentation, declining interests in fur trapping, and other anthropogenic factors can all lead to increased mesopredator populations and these may negatively impact biodiversity. Lethal mesopredator control potentially mitigates some of these effects but can be controversial, largely because impacts on mesopredator populations have not been evaluated. Estimating these impacts may reduce controversies while increasing our understanding of when lethal control may be beneficial. Therefore, we analyzed published mesopredator removal data to determine if mesopredator removal rates changed over time. Removals of medium,(e.g., raccoons (Procyon lotor) or red foxes (Vulpes vulpes), and large, i.e., bobcats (Lynx rufus) or coyotes (Canis latrans), mesopredators were consistent from year to year and over the duration of study (i.e., number removed during the first and last years of studies were similar). In contrast, removals of small mesopredators, e.g., weasels (Mustela spp.) or spotted skunks (Spilogale putorius), declined over the duration of study. Study area size, number of species targeted for removal, and duration of removal effort were poor predictors of removal rates. Our analyses suggest that: (1) control, as typically implemented, is unlikely to cause negative long-term impacts on populations of medium and large mesopredators but may negatively impact small mesopredators, (2) if mesopredator control benefits prey, recurring removals will generally be needed to maintain benefits, and (3) timing of removals will be important to achieve management goals. We suggest that mesopredator control efforts are frequently spatially structured harvests from continuously distributed populations. This may explain (1) why removal of small mesopredators declined over time; whereas, medium and large mesopredator removals remained consistent, and (2) why some prey failed to respond to mesopredator control efforts. PMID- 26361213 TI - Metronomic reloaded: Theoretical models bringing chemotherapy into the era of precision medicine. AB - Oncology has benefited from an increasingly growing number of groundbreaking innovations over the last decade. Targeted therapies, biotherapies, and the most recent immunotherapies all contribute to increase the number of therapeutic options for cancer patients. Consequently, substantial improvements in clinical outcomes for some disease with dismal prognosis such as lung carcinoma or melanoma have been achieved. Of note, the latest innovations in targeted therapies or biotherapies do not preclude the use of standard cytotoxic agents, mostly used in combination. Importantly, and despite the rise of bioguided (a.k.a. precision) medicine, the administration of chemotherapeutic agents still relies on the maximum tolerated drug (MTD) paradigm, a concept inherited from theories conceptualized nearly half a century ago. Alternative dosing schedules such as metronomic regimens, based upon the repeated and regular administration of low doses of chemotherapeutic drugs, and adaptive therapy (i.e. modulating the dose and frequency of cytotoxics administration to control disease progression rather than eradicate it at all cost) have emerged as possible strategies to improve response rates while reducing toxicities. The recent changes in paradigm in the way we theorize cancer biology and evolution, metastatic spreading and tumor ecology, alongside the recent advances in the field of immunotherapy, have considerably strengthened the interest for these alternative approaches. This paper aims at reviewing the recent evolutions in the field of theoretical biology of cancer and computational oncology, with a focus on the consequences these changes have on the way we administer chemotherapy. Here, we advocate for the development of model-guided strategies to refine doses and schedules of chemotherapy administration in order to achieve precision medicine in oncology. PMID- 26361212 TI - Partial Support Ventilation and Mitochondrial-Targeted Antioxidants Protect against Ventilator-Induced Decreases in Diaphragm Muscle Protein Synthesis. AB - Mechanical ventilation (MV) is a life-saving intervention in patients in respiratory failure. Unfortunately, prolonged MV results in the rapid development of diaphragm atrophy and weakness. MV-induced diaphragmatic weakness is significant because inspiratory muscle dysfunction is a risk factor for problematic weaning from MV. Therefore, developing a clinical intervention to prevent MV-induced diaphragm atrophy is important. In this regard, MV-induced diaphragmatic atrophy occurs due to both increased proteolysis and decreased protein synthesis. While efforts to impede MV-induced increased proteolysis in the diaphragm are well-documented, only one study has investigated methods of preserving diaphragmatic protein synthesis during prolonged MV. Therefore, we evaluated the efficacy of two therapeutic interventions that, conceptually, have the potential to sustain protein synthesis in the rat diaphragm during prolonged MV. Specifically, these experiments were designed to: 1) determine if partial support MV will protect against the decrease in diaphragmatic protein synthesis that occurs during prolonged full-support MV; and 2) establish if treatment with a mitochondrial-targeted antioxidant will maintain diaphragm protein synthesis during full-support MV. Compared to spontaneously breathing animals, full support MV resulted in a significant decline in diaphragmatic protein synthesis during 12 hours of MV. In contrast, diaphragm protein synthesis rates were maintained during partial support MV at levels comparable to spontaneous breathing animals. Further, treatment of animals with a mitochondrial-targeted antioxidant prevented oxidative stress during full support MV and maintained diaphragm protein synthesis at the level of spontaneous breathing animals. We conclude that treatment with mitochondrial-targeted antioxidants or the use of partial-support MV are potential strategies to preserve diaphragm protein synthesis during prolonged MV. PMID- 26361214 TI - Microwave-assisted hydrothermal synthesis of Ag2(W(1-x)Mox)O4 heterostructures: Nucleation of Ag, morphology, and photoluminescence properties. AB - Ag2W(1-x)MoxO4 (x=0.0 and 0.50) powders were synthesized by the co-precipitation (drop-by-drop) method and processed using a microwave-assisted hydrothermal method. We report the real-time in situ formation and growth of Ag filaments on the Ag2W(1-x)MoxO4 crystals using an accelerated electron beam under high vacuum. Various techniques were used to evaluate the influence of the network-former substitution on the structural and optical properties, including photoluminescence (PL) emission, of these materials. X-ray diffraction results confirmed the phases obtained by the synthesis methods. Raman spectroscopy revealed significant changes in local order-disorder as a function of the network former substitution. Field-emission scanning electron microscopy was used to determine the shape as well as dimensions of the Ag2W(1-x)MoxO4 heterostructures. The PL spectra showed that the PL-emission intensities of Ag2W(1-x)MoxO4 were greater than those of pure Ag2WO4, probably because of the increase of intermediary energy levels within the band gap of the Ag2W(1-x)MoxO4 heterostructures, as evidenced by the decrease in the band-gap values measured by ultraviolet-visible spectroscopy. PMID- 26361216 TI - Pyrazine motif containing hexagonal macrocycles: synthesis, characterization, and host-guest chemistry with nitro aromatics. AB - The synthesis and characterization of cationic two-dimensional metallamacrocycles having a hexagonal shape and cavity are described. Both macrocycles utilize a pyrazine motif containing an organometallic acceptor tecton with platinum(II) centers along with different donor ligands. While one macrocycle is a relatively larger [6 + 6], the other is a relatively smaller [2 + 2] polygon. A unique feature of the smaller ensemble is that it is an irregular polygon in which all six edges are not of equal length. Molecular modeling of these macrocycles confirmed the presence of hexagonal cavities. The ability of these pi-electron rich macrocycles to act as potential hosts for relatively electron deficient nitroaromatics (DNT = 2,4-dinitrotoluene and PA = picric acid) has been studied using isothermal titration calorimetry (ITC) as a tool. Molecular dynamics simulation studies were subsequently performed to gain critical insight into the binding interactions between the nitroaromatic guest molecules (PA/DNT) and the ionic macrocycles reported herein. PMID- 26361215 TI - Validation of the Cepstral Spectral Index of Dysphonia (CSID) as a Screening Tool for Voice Disorders: Development of Clinical Cutoff Scores. AB - OBJECTIVES: The purposes of this study were to (1) evaluate the performance of the Cepstral Spectral Index of Dysphonia (CSID--a multivariate estimate of dysphonia severity) as a potential screening tool for voice disorder identification and (2) identify potential clinical cutoff scores to classify voice-disordered cases versus controls. METHODOLOGY: Subjects were 332 men and women (116 men, 216 women) comprised of subjects who presented to a physician with a voice-related complaint and a group of non-voice-related control subjects. Voice-disordered cases versus controls were initially defined via three reference standards: (1) auditory-perceptual judgment (dysphonia +/-); (2) Voice Handicap Index (VHI) score (VHI +/-); and (3) laryngoscopic description (laryngoscopic +/ ). Speech samples were analyzed using the Analysis of Dysphonia in Speech and Voice program. Cepstral and spectral measures were combined into a CSID multivariate formula which estimated dysphonia severity for Rainbow Passage samples (i.e., the CSIDR). The ability of the CSIDR to accurately classify cases versus controls in relation to each reference standard was evaluated via a combination of logistic regression and receiver operating characteristic (ROC) analyses. RESULTS: The ability of the CSIDR to discriminate between cases and controls was represented by the "area under the ROC curve" (AUC). ROC classification of dysphonia-positive cases versus controls resulted in a strong AUC = 0.85. A CSIDR cutoff of ~24 achieved the best balance between sensitivity and specificity, whereas a more liberal cutoff score of ~19 resulted in higher sensitivity while maintaining respectable specificity which may be preferred for screening purposes. Weaker but adequate AUCs = 0.75 and 0.73 were observed for the classification of VHI-positive and laryngoscopic-positive cases versus controls, respectively. Logistic regression analyses indicated that subject age may be a significant covariate in the discrimination of dysphonia-positive and VHI-positive cases versus controls. CONCLUSIONS: The CSIDR can provide a strong level of accuracy for the classification of voice-disordered cases versus controls, particularly when auditory-perceptual judgment is used as the reference standard. Although users often focus on a cutoff score that achieves a balance between sensitivity and specificity, more liberal cutoffs for screening purposes versus conservative cutoffs when cost or risk of further evaluation is deemed to be high should also be considered. PMID- 26361217 TI - Children With Mental Disorders Who Receive Disability Benefits: A Report From the IOM. PMID- 26361218 TI - MicroRNA-150 Inhibits Cell Invasion and Migration and Is Downregulated in Human Osteosarcoma. AB - miR-150 expression in osteosarcoma (OS) cell lines and human osteoblast cells was detected, and OS cell models were transfected with exogenous miR-150 to investigate its role in cell proliferation, invasion, and apoptosis. Our results showed that miR-150 expression in OS cells (MG63, Saos-2, SOSP-9607, and U2OS) was significantly lower compared to the osteoblast hFOB1.19 cell line (all p < 0.01). The expression level of miR-150 in MG63 cells that were transfected with exogenous miR-150 mimics was markedly upregulated, while the miR-150 expression level in the inhibitor group was significantly downregulated (both p < 0.01). Similar results were also found in SOSP-9607 cells. Importantly, exogenous miR 150 expression stimulated cell apoptosis and inhibited proliferation, invasion, and migration. A luciferase reporter assay displayed that miR-150 also regulated Sp1 expression by targeting its 3'-UTR, and qRT-PCR and Western blotting showed that elevated levels of miR-150 may reduce Sp1 protein expression. The mRNA and protein levels of Sp1 were upregulated after transfection with a Sp1-expression plasmid and partially reversed the inhibitory effects of miR-150 on cell proliferation, invasion, and metastasis in MG63 and SOSP-9607 cells, as well as promoted cell apoptosis. In conclusion, miR-150 inhibits cell proliferation, invasion, and metastasis and stimulates cell apoptosis by regulating the expression of Sp1. Therefore, miR-150 may be a potential clinical target for the treatment of OS patients. PMID- 26361219 TI - A Particular River-Whiting Phenomenon Caused by Discharge of Hypolimnetic Water from a Stratified Reservoir. AB - A particular river-whiting phenomenon occurred in the early 2000s in the Xiaoche River and since then it has been reoccurring from June to November each year. Residents were surprised by this phenomenon and worried about it. This study was designed to reveal the forming mechanism of the river-whiting phenomenon. A comparison of T, EC, ORP, DO, TDS and delta34S in the culvert water and discharge pipe water with that in the water column of Aha Reservoir strongly indicated that the culvert water and discharge pipe water derived primarily from the hypolimnetic reservoir water. When the hypolimnetic water enriched in SO42- and H2S, through seepage from the penstock, flows into the Xiaoche River, the water's supersaturation degree with respect to CaSO4 is increased as a result of increased temperature and DO, thus colloid CaSO4 can be formed. This is the essential cause of the river-whiting phenomenon. The sources of high concentrations of SO42- and H2S in hypolimnetic water include not only direct SO42- and H2S input of acid mine drainage as a result of irrational coal mining in the watershed, but also the sulfur-enriched surface sediments which may release H2S through the sulfate reduction processes. The contaminated sediment has acted as an important contamination source for sulfur to the overlying water in Aha Reservoir. There are more than 50,000 large dams in the world until now. With the increase of reservoir age and the persistent accumulation of pollutants within the reservoir system, discharged hypolimnetic water may contain high levels of pollutants and lead to unpredicted disasters. More investigations are needed to illuminate the water quality condition of discharge water from reservoirs and estimate its impacts on the downstream eco-environment. PMID- 26361220 TI - A cross-sectional audit of the prevalence of stunting in children attending a regional paediatric cardiology service. AB - CHD is associated with poor growth, delayed motor and language skills development, and increased length of hospital stay; 28.2% of infants were stunted, with z-scores<-2. The severity of surgery score was not associated with an increased length of stay, suggesting that a low weight-for-age z-score at the time of surgery may impact on length of stay. PMID- 26361222 TI - FDG PET and Split-Bolus Multi-Detector Row CT Fusion Imaging in Oncologic Patients: Preliminary Results. AB - PURPOSE: To assess the incremental value of split-bolus multidetector computed tomography (CT) combined with fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) for follow-up of oncologic patients. MATERIALS AND METHODS: The institutional ethics committee approved the use of this protocol. Thirty-eight oncologic patients who underwent FDG PET/unenhanced multidetector CT and split-bolus multidetector CT for restaging were investigated retrospectively. The split-bolus CT protocol included imaging during the hepatic arterial and portal venous phases in one scan. Software was used for fusion of the independently acquired FDG PET and split-bolus CT data, and fused datasets were compared with FDG PET/unenhanced CT data. The standard of reference for diagnosis of lesions in all patients was a combination of histologic results (if available), clinical results (medical history, physical examination, and laboratory test results), and the results of follow-up imaging (conventional CT, magnetic resonance imaging, and/or ultrasonography) for at least 6 months. Descriptive statistics were used. RESULTS: Fifty-nine true-positive lesions were identified with fused FDG PET/split-bolus CT; 41 were concordant and detected with both split-bolus CT and PET/unenhanced CT, 16 with split-bolus CT only, and two with PET/unenhanced CT. Two different false-positive lesions were identified with PET/unenhanced CT and PET/split-bolus CT. Furthermore, in 20 of 38 (53%) patients, FDG PET/split-bolus CT allowed detection of important additional findings (n = 40) not detected at FDG PET/unenhanced CT. Both the tumor-related findings (n = 13, 32.5%) and the non-tumor-related findings (n = 27, 67.5%) were important to the clinical treatment of these patients. CONCLUSION: Fused FDG PET/split-bolus multidetector CT provides additional information compared with FDG PET/unenhanced multidetector CT in oncologic patients. PMID- 26361221 TI - Exaggerated Nighttime Sleep and Defective Sleep Homeostasis in a Drosophila Knock In Model of Human Epilepsy. AB - Despite an established link between epilepsy and sleep behavior, it remains unclear how specific epileptogenic mutations affect sleep and subsequently influence seizure susceptibility. Recently, Sun et al. (2012) created a fly knock in model of human generalized epilepsy with febrile seizures plus (GEFS+), a wide spectrum disorder characterized by fever-associated seizing in childhood and lifelong affliction. GEFS+ flies carry a disease-causing mutation in their voltage-gated sodium channel (VGSC) gene and display semidominant heat-induced seizing, likely due to reduced GABAergic inhibitory activity at high temperature. Here, we show that at room temperature the GEFS+ mutation dominantly modifies sleep, with mutants exhibiting rapid sleep onset at dusk and increased nighttime sleep as compared to controls. These characteristics of GEFS+ sleep were observed regardless of sex, mating status, and genetic background. GEFS+ mutant sleep phenotypes were more resistant to pharmacologic reduction of GABA transmission by carbamazepine (CBZ) than controls, and were mitigated by reducing GABAA receptor expression specifically in wake-promoting pigment dispersing factor (PDF) neurons. These findings are consistent with increased GABAergic transmission to PDF neurons being mainly responsible for the enhanced nighttime sleep of GEFS+ mutants. Additionally, analyses under other light conditions suggested that the GEFS+ mutation led to reduced buffering of behavioral responses to light on and off stimuli, which contributed to characteristic GEFS+ sleep phenotypes. We further found that GEFS+ mutants had normal circadian rhythms in free-running dark conditions. Interestingly, the mutants lacked a homeostatic rebound following mechanical sleep deprivation, and whereas deprivation treatment increased heat-induced seizure susceptibility in control flies, it unexpectedly reduced seizure activity in GEFS+ mutants. Our study has revealed the sleep architecture of a Drosophila VGSC mutant that harbors a human GEFS+ mutation, and provided unique insight into the relationship between sleep and epilepsy. PMID- 26361223 TI - Impact of post-anthesis rainfall, fungicide and harvesting time on the concentration of deoxynivalenol and zearalenone in wheat. AB - Field experiments were conducted to identify the impact of post-anthesis rainfall on the concentration of deoxynivalenol (DON) and zearalenone (ZON) in harvested wheat grain. Winter wheat plots were inoculated with Fusarium graminearum at stem extension (GS31) and prothioconazole was applied at mid-anthesis (GS65) to split plots and plots were subsequently mist irrigated for 5 days. Plots were either covered by polytunnels, irrigated by sprinklers or left as non-irrigated uncovered control plots after medium-milk (GS75). Plots were harvested either when ripe (GS92; early harvest) or three weeks later (late harvest). Fusarium head blight (FHB) was assessed each week from inoculation. At harvest, yield and grain quality was measured and grains were analysed for DON and ZON. Differences in rainfall resulted in contrasting disease pressure in the two experiments, with low FHB in the first experiment and high FHB in the second. Difference in FHB resulted in large differences in grain yield, quality and mycotoxin content. DON concentration was significantly (P < 0.05) higher in irrigated compared to covered and control plots in the first experiment, whereas in the second experiment, DON was significantly (P < 0.05) higher in the covered plots compared to the control and irrigated plots. ZON concentration was significantly (P < 0.05) higher in irrigated plots in both experiments. Later harvesting resulted in an approximate fivefold increase in ZON in the first experiment, but was not significantly different in the second experiment. Prothioconazole significantly (P < 0.05) reduced DON in both experiments, but gave inconsistent reductions to ZON. This is the first report to show that the post-anthesis rainfall can significantly increase ZON in wheat, which can increase further with a delayed harvest but may be significantly reduced with the application of prothioconazole. Importantly, in the absence of moisture late season, ZON remains at very low concentrations even when wheat is severely affected by FHB. PMID- 26361224 TI - Novel hollow all-carbon structures. AB - A new family of cavernous all-carbon structures is proposed. These molecular cage structures are constructed by edge subdivisions and leapfrog transformations from cubic polyhedra or their duals. The obtained structures were then optimized at the density functional level. These hollow carbon structures represent a new class of carbon allotropes which could lead to many interesting applications. PMID- 26361225 TI - Period Prevalence of Dizziness and Vertigo in Adolescents. AB - OBJECTIVES: To assess the period prevalence and severity of dizziness and vertigo in adolescents. METHODS: In 1661 students in 8th-10th grade in twelve grammar schools in Munich, Germany information on vertigo/dizziness was assessed by a questionnaire in the class room setting. Three month prevalence of dizziness/vertigo was estimated; symptoms were categorized as orthostatic dizziness, spinning vertigo, swaying vertigo or unspecified dizziness. Duration of symptoms and impact on daily life activities were assessed. RESULTS: 72.0% (95%-CI = [69.8-74.2]; N = 1196) of the students (mean age 14.5+/-1.1) reported to suffer from at least one episode of dizziness or vertigo in the last three months. Most adolescents ticked to have symptoms of orthostatic dizziness (52.0%, 95%-CI = [49.5-54.4], N = 863). The period prevalence for the other types of vertigo were spinning vertigo: 11.6%, 95%-CI = [10.1-13.3], N = 193; swaying vertigo: 12.2%, 95%-CI = [10.6-13.8], N = 202; and unspecified dizziness: 15.2%, 95%-CI = [13.5-17.1], N = 253. About 50% of students with spinning vertigo and swaying vertigo also report to have orthostatic dizziness. Most vertigo/dizziness types were confined to less than one minute on average. The proportion of students with any dizziness/vertigo accounting for failure attending school, leisure activities or obliging them to stay in bed were more pronounced for spinning or swaying vertigo. CONCLUSION: Dizziness and vertigo in grammar school students appear to be as common as in adults. In face of the high period prevalence and clinical relevance of dizziness/vertigo in adolescents there is a need for prevention strategies. Risk factors for dizziness/vertigo need to be assessed to allow for conception of an intervention programme. PMID- 26361226 TI - Sleep patterns in Amazon rubber tappers with and without electric light at home. AB - Today's modern society is exposed to artificial electric lighting in addition to the natural light-dark cycle. Studies assessing the impact of electric light exposure on sleep and its relation to work hours are rare due to the ubiquitous presence of electricity. Here we report a unique study conducted in two phases in a homogenous group of rubber tappers living and working in a remote area of the Amazon forest, comparing those living without electric light (n = 243 in first phase; n = 25 in second phase) to those with electric light at home (n = 97 in first phase; n = 17 in second phase). Questionnaire data (Phase 1) revealed that rubber tappers with availability of electric light had significantly shorter sleep on work days (30 min/day less) than those without electric light. Analysis of the data from the Phase 2 sample showed a significant delay in the timing of melatonin onset in workers with electric light compared to those without electric light (p < 0.01). Electric lighting delayed sleep onset and reduced sleep duration during the work week and appears to interfere with alignment of the circadian timing system to the natural light/dark cycle. PMID- 26361227 TI - Structure Based Thermostability Prediction Models for Protein Single Point Mutations with Machine Learning Tools. AB - Thermostability issue of protein point mutations is a common occurrence in protein engineering. An application which predicts the thermostability of mutants can be helpful for guiding decision making process in protein design via mutagenesis. An in silico point mutation scanning method is frequently used to find "hot spots" in proteins for focused mutagenesis. ProTherm (http://gibk26.bio.kyutech.ac.jp/jouhou/Protherm/protherm.html) is a public database that consists of thousands of protein mutants' experimentally measured thermostability. Two data sets based on two differently measured thermostability properties of protein single point mutations, namely the unfolding free energy change (ddG) and melting temperature change (dTm) were obtained from this database. Folding free energy change calculation from Rosetta, structural information of the point mutations as well as amino acid physical properties were obtained for building thermostability prediction models with informatics modeling tools. Five supervised machine learning methods (support vector machine, random forests, artificial neural network, naive Bayes classifier, K nearest neighbor) and partial least squares regression are used for building the prediction models. Binary and ternary classifications as well as regression models were built and evaluated. Data set redundancy and balancing, the reverse mutations technique, feature selection, and comparison to other published methods were discussed. Rosetta calculated folding free energy change ranked as the most influential features in all prediction models. Other descriptors also made significant contributions to increasing the accuracy of the prediction models. PMID- 26361228 TI - Evaluation of a 345 nm Femtosecond Laser for Corneal Surgery with Respect to Intraocular Radiation Hazard. AB - PURPOSE: We report our findings from a preclinical safety study designed to assess potential side effects of corneal ultraviolet femtosecond laser treatment on lens and retina. METHODS: Refractive lenticules (-5 dpt) with a diameter of 6 mm were created in the right cornea of eight Dutch Belted rabbits. Radiant exposure was 0.5 J/cm2 in two animals and 18 J/cm2 in six animals. The presence of lens opacities was assessed prior to and up to six months following laser application using Scheimpflug images (Pentacam, Oculus) and backscatter analysis (Opacity Lensmeter 702, Interzeag). Ganzfeld flash and flicker electroretinogram (ERG) recordings were obtained from both eyes prior to and up to six weeks following laser application. At the study endpoint, retinas were examined by light microscopy. RESULTS: Independent of energy dose applied, no cataract formation could be observed clinically or with either of the two objective methods used. No changes in ERG recordings over time and no difference between treated and untreated eye were detected. Histologically, retinal morphology was preserved and retinal pigment epithelium as well as photoreceptor inner and outer segments appeared undamaged. Quantitative digital image analysis did not reveal cell loss in inner or outer nuclear layers. CONCLUSIONS: Our analysis confirms theoretical considerations suggesting that ultraviolet femtosecond laser treatment of the cornea is safe for intraocular tissues. Transmitted light including stray light induces no photochemical effects in lens or retina at energy levels much higher than required for the clinical purpose. These conclusions cannot be applied to eyes with pre-existing retinal damage, as these may be more vulnerable to light. PMID- 26361230 TI - A comparative study on the mechanical properties of the healthy and varicose human saphenous vein under uniaxial loading. AB - Saphenous Vein (SV) due to fatness, age, inactiveness, etc. can be afflicted with varicose. The main reason of the varicose vein is believed to be related to the leg muscle pump which is unable to return the blood to the heart in contradiction of the effect of gravity. As a result of the varicose vein, both the structure and mechanical properties of the vein wall would alter. However, so far there is a lack of knowledge on the mechanical properties of the varicose vein. In this study, a comparative study was carried out to measure the elastic and hyperelastic mechanical properties of the healthy and varicose SVs. Healthy and varicose SVs were removed at autopsy and surgery from seven individuals and then axial tensile load was applied to them up to the failure point. In order to investigate the mechanical behaviour of the vein, this study was benefitted from three different stress definitions, such as 2nd Piola-Kichhoff, engineering and true stresses and four different strain definitions, i.e. Almansi-Hamel, Green St. Venant, engineering and true strains, to determine the linear mechanical properties of the SVs. A Digital Image Correlation (DIC) technique was used to measure the true strain of the vein walls during load bearing. The non-linear mechanical behaviour of the SVs was also computationally evaluated via the Mooney Rivlin material model. The true/Cauchy stress-strain diagram exhibited the elastic modulus of the varicose SVs as 45.11% lower than that of the healthy ones. Furthermore, by variation of the stress a significant alteration on the maximum stress of the healthy SVs was observed, but then not for the varicose veins. Additionally, the highest stresses of 4.99 and 0.65 MPa were observed for the healthy and varicose SVs, respectively. These results indicate a weakness in the mechanical strength of the SV when it becomes varicose, owing to the degradation of the elastin and collagen content of the SV. The Mooney-Rivlin hyperelastic and the Finite Element (FE) data were finally well compared to the experimental data. PMID- 26361229 TI - Indoleamine 2,3-Dioxygenase Is Involved in the Inflammation Response of Corneal Epithelial Cells to Aspergillus fumigatus Infections. AB - Indoleamine 2,3-dioxygenase (IDO), which is mainly expressed in activated dendritic cells, is known as a regulator of immune responses. However, the role of IDO in immune responses against fungal corneal infection has not been investigated. To evaluate the regulatory mechanisms of IDO in fungal inflammation, we resorted to human corneal epithelial cells (HCECs), known as the first barrier of cornea against pathogenic microorganisms. We found that IDO was significantly up-regulated in corneal epithelium infected with Aspergillus fumigatus (A. fumigatus) and HCECs incubated with spores of A. fumigatus. Furthermore, IDO inhibitor (1-methyltryptophan, 1-MT) enhanced inflammatory cytokines IL-1beta and IL-6 expression which were up-regulated by A. fumigatus spores infection. Dectin-1, as one of the important C-type lectin receptors, can identify beta-glucan, and mediate fungal innate immune responses. In the present study, pre-treatment with curdlan, a Dectin-1 agonist, further enhanced IDO expression compared with A. fumigatus stimulation. While laminarin, the Dectin-1 specific inhibitor, partially inhibited IDO expression stimulated by A. fumigatus. Further studies demonstrated inhibition of IDO activity amplified the expressions of inflammatory cytokines IL-1beta and IL-6 induced by activation of Dectin-1. These results suggested that IDO was involved in the immune responses of fungal keratitis. The activation of Dectin-1 may contribute to A. fumigatus spores-induced up-regulation of IDO. PMID- 26361231 TI - Dipeptidyl peptidase-4 inhibitors in triple oral therapy regimens in patients with type 2 diabetes mellitus. AB - OBJECTIVE: There is no clear consensus regarding treatment of patients with type 2 diabetes mellitus (T2DM) that is inadequately controlled using dual combination therapy. Recommended agents for triple combination therapy should have complementary mechanisms of action with minimal risk of added side effects such as weight gain and hypoglycemia. We discuss considerations in selecting triple oral therapy regimens in patients with T2DM, and review clinical trial data regarding triple oral therapy using dipeptidyl peptidase-4 (DPP-4) inhibitors. METHODS: A search of the PubMed database was conducted to identify clinical trials of triple oral therapy incorporating a DPP-4 inhibitor (November 2013 to January 2015), using the following search terms: 'type 2 diabetes' AND 'alogliptin OR linagliptin OR saxagliptin OR sitagliptin OR vildagliptin' AND 'metformin'. Trials had to include adult patients with T2DM who received triple oral therapy with a DPP-4 inhibitor for >=18 weeks. The bibliographies of retrieved articles were also searched to identify any other relevant trials. RESULTS: A total of 17 clinical trials evaluating metformin and a DPP-4 inhibitor combined with a sulfonylurea (SU), thiazolidinedione (TZD), or sodium-glucose cotransporter 2 (SGLT2) inhibitor were identified and included in this review. Consistently, the addition of a DPP-4 inhibitor to metformin and SU, TZD, or SGLT2 inhibitor therapy improved glycemic measures, and these combinations were generally well tolerated. An increased incidence of hypoglycemia was reported for combinations that included an SU. CONCLUSIONS: Triple oral therapy that includes a DPP-4 inhibitor is a valid option for patients with T2DM not adequately controlled with dual combination therapy, and offers an alternative to insulin therapy. Triple oral therapy with a DPP-4 inhibitor, metformin, and a TZD or SGLT2 inhibitor should be considered when avoidance of hypoglycemia is a primary goal. PMID- 26361232 TI - Negative emotional responses to motherhood-related support receipt during pregnancy predict postpartum depressive symptoms. AB - BACKGROUND AND OBJECTIVES: Prenatal stress increases risk for postpartum depression. While social support availability may attenuate this risk, little research has examined support receipt during pregnancy, which has been linked to increased distress in other domains. This study assesses the implications of motherhood-related and motherhood-unrelated support receipt for daily distress during pregnancy and tests whether negative responsiveness to motherhood-related support predicts postpartum depression risk. DESIGN AND METHOD: Thirty-one pregnant women were recruited from the community for a 3-wave study (beginning at approximately 26 weeks gestation, 34 weeks gestation, and 4 weeks postpartum). Each wave included a survey of general characteristics (e.g. depressive symptoms) and a two-week diary period measuring mood, stress, and support. RESULTS: A multilevel model analysis suggested that motherhood-related support predicted greater increases in daily distress than motherhood-unrelated support. Follow-up regression analysis showed that those who responded more negatively to motherhood related support reported higher postpartum depressive symptoms. CONCLUSIONS: Although preliminary due to the sample size, the results suggest that how women interpret and respond to support may contribute to postpartum depression risk. Future research should focus on how mothers can more positively construe the support they receive in addition to how to increase the support available to them. PMID- 26361233 TI - Navigating the thin-ideal in an athletic world: influence of coach communication on female athletes' body image and health choices. AB - This study sought to investigate how interpersonal communication between coaches and female athletes influences the female athletes' perceptions of body image and health choices. Much of the current literature has focused on the fact that female athletes are at risk for disordered eating and a distorted body image due to susceptibility to the feminine "thin-ideal" while maintaining the fitness levels necessary to compete in their sport. However, very little research has examined how interpersonal interaction plays a role in female athletes' body image perceptions and health behaviors. Utilizing the Communication Theory of Identity (CTI) as a lens to examine communication between female athletes and their coaches, the researchers analyzed transcripts from in-depth interviews with 28 female athletes and identified themes within the personal, relational, enacted, and communal layers of identity. Coach communication with their female athletes was found to be influential to the athletes' body images and health choices. PMID- 26361234 TI - Synthesis of colloidal InSb nanocrystals via in situ activation of InCl3. AB - Indium antimonide (InSb), a narrow band gap III-V semiconductor is a promising infrared-active material for various optoelectronic applications. Synthetic challenge of colloidal InSb nanocrystals (NCs) lies in the limited choice of precursors. Only a few successful synthetic schemes involving highly toxic stibine (SbH3) or air- and moisture-sensitive metal silylamides (In[N(Si (Me)3)2]3 or Sb[N(Si-(Me)3)2]3) as the precursor have been reported. We found that commercially available precursors InCl3 and Sb[NMe2]3 directly form highly crystalline colloidal InSb nanocrystals in the presence of a base such as LiN(SiMe3)2 or nBuLi. The mean size of the particles can be controlled by simply changing the activating base. This approach offers a one-pot synthesis of InSb NCs from readily available chemicals without the use of complex organometallic precursors. PMID- 26361235 TI - ELICIT: An alternative imprecise weight elicitation technique for use in multi criteria decision analysis for healthcare. AB - OBJECTIVE: In this paper, the readers are introduced to ELICIT, an imprecise weight elicitation technique for multicriteria decision analysis for healthcare. METHODS: The application of ELICIT consists of two steps: the rank ordering of evaluation criteria based on decision-makers' (DMs) preferences using the principal component analysis; and the estimation of criteria weights and their descriptive statistics using the variable interdependent analysis and the Monte Carlo method. The application of ELICIT is illustrated with a hypothetical case study involving the elicitation of weights for five criteria used to select the best device for eye surgery. RESULTS: The criteria were ranked from 1-5, based on a strict preference relationship established by the DMs. For each criterion, the deterministic weight was estimated as well as the standard deviation and 95% credibility interval. CONCLUSIONS: ELICIT is appropriate in situations where only ordinal DMs' preferences are available to elicit decision criteria weights. PMID- 26361236 TI - A comparison between combined open bypass revascularization and free tissue transfer versus endovascular revascularization and free tissue transfer for lower limb preservation. AB - BACKGROUND: Extensive defects of the lower limb as a result of diabetes and peripheral vascular disease require multidisciplinary treatment. Numerous studies with regards combining vascular bypass surgery and free tissue reconstruction of the lower limb had been published. However the trend has evolved toward a combination of endovascular revascularization and free flap reconstruction. The aim of this study was to compare the safety and efficacy of this combination of treatment to the traditional combination of bypass surgery and free tissue reconstruction. METHODS: All patients who had undergone vascular bypass surgery and free tissue reconstruction of the lower limb as well as those who had undergone endovascular angioplasty with free tissue transfer for lower limb preservation, over a 10-year period was included in this study. RESULTS: A total of 46 patients that underwent limb preservation were included in this study, 22 patients underwent open bypass revascularization and free flap transfer and 24 patients underwent endovascular revascularization and free tissue transfer. There were no differences between the two methods with regards to age, sex, defect size, TransAtlantic InterSociety Consensus level, Wagner classification, length of hospitalization, limb preservation rate, total flap necrosis rate, and partial flap necrosis rate. More importantly, there was no significant difference in the limb preservation rate (P = 0.14). CONCLUSION: In this study we found that the safety and the success rate of lower limb preservation using a combination of endovascular revascularization and free tissue reconstruction is comparable to using a combination of bypass surgery and free tissue transfer. PMID- 26361237 TI - Serum Shiga toxin 2 values in patients during acute phase of diarrhoea-associated haemolytic uraemic syndrome. AB - AIM: Shiga toxins are delivered via systemic circulation and are considered to be the cause of diarrhoea-associated haemolytic uraemic syndrome (HUS), as they injure endothelial cells, particularly in the glomeruli. This study measured Shiga toxin 2 (Stx2) in the serum of children affected in by HUS due to Stx2 producing Escherichia coli. METHODS: The concentration of free Stx2 was measured in the serum of 16 children, collected immediately after admission to the clinic in the acute phase of HUS, using a sandwich enzyme-linked immunosorbent assay. The family members of two children were also investigated, with the relative toxicity of Stx2 assessed by a Vero cell-based fluorescent assay. RESULTS: Stx2 was found in the serum of eight of the 16 children who were investigated. It was also detected in four of the six family members not showing symptomatic HUS, with an extremely high level in two. CONCLUSION: An absent or rather low concentration of Stx2 was found in the serum of children admitted to the clinic with diarrhoea associated HUS. The high concentration of Stx2 in family members without HUS, but mostly with watery diarrhoea and raised functional activity, was in line with the concept of early injury by Stx2. PMID- 26361238 TI - Evaluation of dual-arc VMAT radiotherapy treatment plans automatically generated via dose mimicking. PMID- 26361239 TI - Restoring Congenitally Missing Maxillary Lateral Incisors Using Zirconia-Based Resin Bonded Prostheses. AB - OBJECTIVE: This clinical report describes an alternative treatment modality for the replacement of congenitally missing maxillary lateral incisors in a 17-year old patient. CLINICAL CONSIDERATIONS: Zirconia-based resin-bonded fixed partial dentures (RBFPDs) were selected as a viable and conservative treatment option in a young individual with highly aesthetic expectations. Fabrication of all-ceramic RBFPDs followed specific preparation design and features to accommodate two retainers. The zirconia frameworks with bilateral wings were digitally designed and then milled by a computer-aided design and computer-aided manufacturing (CAD/CAM)-controlled milling machine. Zirconia surface was treated with a two step chairside tribochemical silica-coating/silane coupling surface treatment protocol, and adhesive resin luting cement was used to achieve micromechanical and chemical bonding. Completion of the treatment resulted in a functional and aesthetic successful outcome and a 17-month follow-up presented uneventful. CONCLUSION: Contemporary adhesive techniques involving resin-bonded zirconia based prostheses can be utilized successfully and predictably in young patients with single missing teeth when implant therapy is currently not a treatment of choice and a less invasive approach is desired. CLINICAL SIGNIFICANCE: The zirconia-based resin-bonded prosthesis constitutes a viable and conservative treatment modality for the replacement of missing teeth either congenitally or from another etiology in young patients in which implant therapy and a fixed partial denture are currently contraindicated. PMID- 26361240 TI - Optical and surface properties of the in doped GaAs layer deposition using thermionic vacuum arc method. AB - A broadband optical transparent InGaAs semiconductor layer production of micron thicknesses was produced in only 75 s by thermionic vacuum arc (TVA) method at the first time. The optical and surface properties of the produced layers have been investigated. InGaAs structure is using in electronics and optoelectronics devices. The main advantage of TVA method is its fast deposition rate, without any loss in the quality of the films. Doping is a very simple and fast according to common production methods. InGaAs is an alloy of indium arsenide (InAs) and gallium arsenide (GaAs). InAs with (220) crystallographic direction and GaAs with (024)/(022) crystallographic directions were detected using by XRD analysis. GaAs and InAs are in the cubic and zinc blende crystal system, respectively. According to the transmittance spectra, sample has a broadband transparency in the range of 1000-3300 nm. According to results, defined TVA method for In doping to GaAs is proper fast and friendly method. SCANNING 38:297-302, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26361241 TI - Outcome in patients treated with isolated liver transplantation for familial transthyretin amyloidosis to prevent cardiomyopathy. AB - BACKGROUND: Familial transthyretin (TTR) amyloidosis is caused by different TTR mutations resulting in different clinical phenotypes of the disease. The Leu111Met mutation causes severe restrictive cardiomyopathy. Liver transplantation (LTx) is an established treatment option for patients with TTR amyloidosis; however, information on outcome after isolated LTx in patients with Leu111Met mutation amyloidosis is limited. METHODS: Between 2005 and 2012, six patients with TTR Leu111Met amyloidosis underwent isolated orthotopic LTx. None suffered from neuropathy. Prior to LTx, patients presented with echocardiographic manifestations of early cardiac amyloid involvement and in five endomyocardial biopsy was positive for TTR amyloid. RESULTS: Median age at LTx was 45.5 yr (range 39-54), and four were male (67%). All patients were alive at a median follow-up of 56.6 months (range 18-104). No surgical complications occurred. Two patients (33%) underwent cardiac transplantation during follow-up due to progressive cardiomyopathy. The remaining four patients experienced no echocardiographic or clinical deterioration of cardiac function following LTx. CONCLUSION: Isolated LTx appears to be a valuable treatment option for patients with familial TTR amyloidosis due to Leu111Met mutation. Appropriate timing of LTx is of utmost importance to avoid development of severe amyloid cardiomyopathy and the need for combined heart and liver transplantation. PMID- 26361242 TI - Donor Hemodynamics as a Predictor of Outcomes After Kidney Transplantation From Donors After Cardiac Death. AB - Donation after cardiac death is an important source of transplantable organs, but evidence suggests donor warm ischemia contributes to inferior outcomes. Attempts to predict recipient outcome using donor hemodynamic measurements have not yielded statistically significant results. We evaluated novel measures of donor hemodynamics as predictors of delayed graft function and graft failure in a cohort of 1050 kidneys from 566 donors. Hemodynamics were described using regression line slopes, areas under the curve, and time beyond thresholds for systolic blood pressure, oxygen saturation, and shock index (heart rate divided by systolic blood pressure). A logistic generalized estimation equation model showed that area under the curve for systolic blood pressure was predictive of delayed graft function (above median: odds ratio 1.42, 95% confidence interval [CI] 1.06-1.90). Multivariable Cox regression demonstrated that slope of oxygen saturation during the first 10 minutes after extubation was associated with graft failure (below median: hazard ratio 1.30, 95% CI 1.03-1.64), with 5-year graft survival of 70.0% (95%CI 64.5%-74.8%) for donors above the median versus 61.4% (95%CI 55.5%-66.7%) for those below the median. Among older donors, increased shock index slope was associated with increased hazard of graft failure. Validation of these findings is necessary to determine the utility of characterizing donor warm ischemia to predict recipient outcome. PMID- 26361243 TI - Immunophenotypic parameters and RBC alloimmunization in children with sickle cell disease on chronic transfusion. AB - Alloimmunization against red blood cell (RBC) antigens is a cause of morbidity and mortality in transfused patients with sickle cell disease (SCD). To investigate distinguishing characteristics of patients who develop RBC alloantibodies after transfusion (responders) versus those who do not (non responders), a cross-sectional study of 90 children with SCD on chronic RBC transfusion therapy at a single institution was conducted in which 18 immune parameters (including T and B cell subsets) were tested via flow cytometry, and medical records were reviewed. RBC alloimmunization was present in 26/90 (29%) patients, with anti-E, K, and C among the most commonly detected alloantibodies despite prophylactic matching for these antigens at the study institution. In addition, RBC autoantibodies had been detected in 18/26 (69%) of alloimmunized versus 7/64 (11%) of non-alloimmunized patients (P < 0.0001). Alloimmunized patients were significantly older (median 13.0 years vs. 10.7 years, P = 0.010) and had more RBC unit exposures (median 148 U vs. 82 U, P = 0.020) than non alloimmunized patients. Sex, age at initiation of chronic transfusion, splenectomy, stroke, and transfusion outside of the study institution were not significantly associated with RBC alloimmunization. Alloimmunized patients had a significantly increased percentage of CD4+ T memory cells compared to non alloimmunized patients (57% vs. 49%, P = 0.0047), with no other significant differences in immune cell subsets or laboratory values detected between these groups. Additional research of RBC alloimmunization is needed to optimize transfusion therapy and to develop strategies to prevent alloimmunization. PMID- 26361244 TI - Facile Synthesis and Properties of 2-lambda(5)-Phosphaquinolines and 2-lambda(5) Phosphaquinolin-2-ones. AB - Treatment of 2-ethynylanilines with P(OPh)3 gives either 2,2-diphenoxy-2 lambda(5)-phosphaquinolines or 2-phenoxy-2-lambda(5)-phosphaquinolin-2-ones under transition-metal-free conditions. This reaction offers access to an underexplored heterocycle, which opens up the study of the fundamental nature of the N=P(V) double bond and its potential for delocalization within a cyclic pi-electron system. This heterocycle can serve as a carbostyril mimic, with application as a bioisostere for pharmaceuticals based on the 2-quinolinone scaffold. It also holds promise as a new fluorophore, since initial screening reveals quantum yields upwards of 40%, Stokes shifts of 50-150 nm, and emission wavelengths of 380-540 nm. The phosphaquinolin-2-ones possess one of the strongest solution state dimerization constants for a D-A system (130 M(-1)) owing to the close proximity of a strong acceptor (P=O) and a strong donor (phosphonamidate N-H), which suggests that they might hold promise as new hydrogen-bonding hosts for optoelectronic sensing. PMID- 26361245 TI - Prescription Opioid Use and Risk of Coronary Heart Disease, Stroke, and Cardiovascular Death Among Adults from a Prospective Cohort (REGARDS Study). AB - OBJECTIVE: Despite unknown risks, prescription opioid use (POU) for nonmalignant chronic pain has grown in the US over the last decade. The objective of this study was to examine associations between POU and coronary heart disease (CHD), stroke, and cardiovascular disease (CVD) death in a large cohort. DESIGN, SETTING, SUBJECTS: POU was assessed in the prospective cohort study of 29,025 participants of the REasons for Geographic and Racial Differences in Stroke study, enrolled between 2003 and 2007 from the continental United States and followed through December 31, 2010. CHD, stroke, and CVD death were expert adjudicated outcome measures. METHODS: Cox proportional hazards models adjusted for CVD risk factors were used. RESULTS: Over a median (SD) of 5.2 (1.8) years of follow-up, 1,362 CHD events, 749 strokes, and 1,120 CVD death occurred (105, 55, and 104, respectively, in the 1,851 opioid users). POU was not associated with CHD (adjusted hazard ratio [aHR]) 1.03 [95% CI 0.83-1.26] or stroke (aHR 1.04 [95% CI 0.78-1.38]), but was associated with CVD death (aHR 1.24 [95% CI 1.00 1.53]) in the overall sample. In the sex-stratified analyses, POU was associated with increased risk of CHD (aHR 1.38 [95% CI 1.05-1.82]) and CVD death (aHR 1.66 [95% CI 1.27-2.17]) among females but not males (aHR 0.70 [95% CI 0.50-0.97] for CHD and 0.78 [95% CI 0.54-1.11] for CVD death). CONCLUSION: Female but not male POU were at higher risk of CHD and CVD death. POU was not associated with stroke in overall or sex-stratified analyses. PMID- 26361246 TI - Incidence of Induced Abortion and Post-Abortion Care in Tanzania. AB - BACKGROUND: Tanzania has one of the highest maternal mortality ratios in the world, and unsafe abortion is one of its leading causes. Yet little is known about its incidence. OBJECTIVES: To provide the first ever estimates of the incidence of unsafe abortion in Tanzania, at the national level and for each of the 8 geopolitical zones (7 in Mainland plus Zanzibar). METHODS: A nationally representative survey of health facilities was conducted to determine the number of induced abortion complications treated in facilities. A survey of experts on abortion was conducted to estimate the likelihood of women experiencing complications and obtaining treatment. These surveys were complemented with population and fertility data to obtain abortion numbers, rates and ratios, using the Abortion Incidence Complications Methodology. RESULTS: In Tanzania, women obtained just over 405,000 induced abortions in 2013, for a national rate of 36 abortions per 1,000 women age 15-49 and a ratio of 21 abortions per 100 live births. For each woman treated in a facility for induced abortion complications, 6 times as many women had an abortion but did not receive care. Abortion rates vary widely by zone, from 10.7 in Zanzibar to 50.7 in the Lake zone. CONCLUSIONS: The abortion rate is similar to that of other countries in the region. Variations by zone are explained mainly by differences in fertility and contraceptive prevalence. Measures to reduce the incidence of unsafe abortion and associated maternal mortality include expanding access to post-abortion care and contraceptive services to prevent unintended pregnancies. PMID- 26361247 TI - Hepatitis B virus in children: More therapeutic options-but unknown and known unknowns still present. PMID- 26361248 TI - Structural brain MRI studies in eye diseases: are they clinically relevant? A review of current findings. AB - Many eye diseases reduce visual acuity or are associated with visual field defects. Because of the well-defined retinotopic organization of the connections of the visual pathways, this may affect specific parts of the visual pathways and cortex, as a result of either deprivation or transsynaptic degeneration. For this reason, over the past several years, numerous structural magnetic resonance imaging (MRI) studies have examined the association of eye diseases with pathway and brain changes. Here, we review structural MRI studies performed in human patients with the eye diseases albinism, amblyopia, hereditary retinal dystrophies, age-related macular degeneration (AMD) and glaucoma. We focus on two main questions. First, what have these studies revealed? Second, what is the potential clinical relevance of their findings? We find that all the aforementioned eye diseases are indeed associated with structural changes in the visual pathways and brain. As such changes have been described in very different eye diseases, in our view the most parsimonious explanation is that these are caused by the loss of visual input and the subsequent deprivation of the visual pathways and brain regions, rather than by transsynaptic degeneration. Moreover, and of clinical relevance, for some of the diseases - in particular glaucoma and AMD - present results are compatible with the view that the eye disease is part of a more general neurological or neurodegenerative disorder that also affects the brain. Finally, establishing structural changes of the visual pathways has been relevant in the context of new therapeutic strategies to restore retinal function: it implies that restoring retinal function may not suffice to also effectively restore vision. Future structural MRI studies can contribute to (i) further establish relationships between ocular and neurological neurodegenerative disorders, (ii) investigate whether brain degeneration in eye diseases is reversible, (iii) evaluate the use of neuroprotective medication in ocular disease, (iv) determine optimal timing for retinal implant insertion and (v) establish structural MRI examination as a diagnostic tool in ophthalmology. PMID- 26361249 TI - The course of psychiatric co-morbidity in patients with breast cancer--results from the prospective multi-centre BRENDA II study. AB - PURPOSE: This study examined the frequency of psychiatric co-morbidity in patients with breast cancer, its changes over time and predictors for these changes. METHODS: In a prospective study with measurements before surgery (t1, baseline), 1 month (t2) and 8 months thereafter (t3) using the Patient Health Questionnaire, we examined the course of psychiatric co-morbidity in breast cancer patients. The co-morbidity courses were grouped into healthy (no co morbidity during the study), acute (co-morbidity at t1 and/or t2, but not at t3), emerging (no co-morbidity at t1, but at t3) and chronic (co-morbidity at t1 and t3). RESULTS: Of the 598 participants, 19% had acute, 10% emerging and 9% chronic psychiatric co-morbidity. Acute co-morbidity was more common in patients with poor quality of life (odds ratio (OR) 9.6, 95% confidence interval (CI) 4.4-20.8) and somatic co-morbidity (OR 3.8, CI 1.1-12.4). Patients who perceived support from their doctors had acute co-morbidity less frequently (OR 0.7, CI 0.5-1.0). Emerging co-morbidity occurred more often in younger patients (OR 2.4, CI 1.2 4.7) and in patients with another cancer in their own (OR 2.0, CI 1.1-3.9) or family (OR 2.1, CI 1.1-4.3) histories, less often in patients with support from doctors (OR 0.6, CI 0.4-1.0). Chronic co-morbidity was related to poor quality of life (OR 12.1, CI 3.6-39.9). CONCLUSION: We found acute and emerging psychiatric co-morbidities less often in patients who reported having a supportive doctor patient relationship. Patients that require psycho-oncological support often have poor quality of life and have experienced cancer before. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26361250 TI - Pattern of gonadal differentiation and development up to sexual maturity in the frogs, Microhyla ornata and Hylarana malabarica: A comparative study. AB - Gonadogenesis was studied in Microhyla ornata (Family: Microhylidae) and Hylarana malabarica (Family: Ranidae) up to sexual maturity. Indifferent gonads of M. ornata directly differentiated into either testes or ovaries while those of H. malabarica differentiated into ovaries in all the individuals followed by testicular differentiation in males through an ovarian phase. In some tadpoles of M. ornata, formation of a central cavity at Gosner stage 27 marked ovary differentiation while meiosis was initiated at stage 29. Folliculogenesis was evident at stage 39. Vitellogenesis was initiated in females 9 months post metamorphosis that attained maturity around 11 months after the completion of metamorphosis. Gonads of males with uniformly distributed germ and somatic cells remained undifferentiated until stage 41. Germ and somatic cells reorganized into seminiferous cords at stage 42. One month after completing metamorphosis, testes contained seminiferous tubules while those of 3 months old males exhibited all spermatogenic stages. In H. malabarica, germ cells entry into meiosis marked ovary differentiation at stage 29 while, ovarian cavity was discernable around stage 35. Post-metamorphosis, ovaries of 1-6 month old females contained pre diplotene oocytes. Females were immature even 1 year after the completion of metamorphosis. In all the tadpoles, ovaries with central cavity and meiocytes were present up to the completion of metamorphosis. Gonads of prospective males displayed an obliterating ovarian cavity along with degenerating oocytes at the end of metamorphosis. Germ and somatic cells reorganized into seminiferous cords in males 3 months after the completion of metamorphosis. Testes of 4 months old males exhibited distinct seminiferous tubules while those of 6 months old exhibited meiosis. All spermatogenic stages were observed in testes of 9 months old males indicating maturity. PMID- 26361251 TI - 5,5'-Diamino-BIPHEP ligands bearing small selector units for non-covalent binding of chiral analytes in solution. AB - A dynamic axially chiral BIPHEP-ligand with 3,5-dichlorobenzoyl amide selector units for non-covalent binding of phenylalanine derivatives has been developed. Interaction studies in solution were performed with rhodium(i) complexes under exclusion of the metal being involved in binding. (Rax, S(Phe)) and (Sax, S(Phe)) adducts were observed as significantly separated species in NMR spectroscopy. PMID- 26361252 TI - Analysis of the Role of Peripheral Ligands Coordinated to Zn(II) in Enhancing the Energy Barrier in Luminescent Linear Trinuclear Zn-Dy-Zn Single-Molecule Magnets. AB - Three new Dy complexes have been prepared according to a complex-as-ligand strategy. Structural determinations indicate that the central Dy ion is surrounded by two LZn units (L(2-) is the di-deprotonated form of the N2 O2 compartmental N,N'-2,2-dimethylpropylenedi(3-methoxysalicylideneiminato) Schiff base. The Dy ions are nonacoordinate to eight oxygen atoms from the two L ligands and to a water molecule. The Zn ions are pentacoordinate in all cases, linked to the N2 O2 atoms from L, and the apical position of the Zn coordination sphere is occupied by a water molecule or bromide or chloride ions. These resulting complexes, formulated (LZnX)-Dy-(LZnX), are tricationic with X=H2 O and monocationic with X=Br or Cl. They behave as field-free single-molecule magnets (SMMs) with effective energy barriers (Ueff ) for the reversal of the magnetization of 96.9(6) K with tau0 =2.4*10(-7) s, 146.8(5) K with tau0 =9.2*10(-8) s, and 146.1(10) K with tau0 =9.9*10(-8) s for compounds with Zn?OH2 , Zn?Br, and Zn?Cl motifs, respectively. The Cole-Cole plots exhibit semicircular shapes with alpha parameters in the range of 0.19 to 0.29, which suggests multiple relaxation processes. Under a dc applied magnetic field of 1000 Oe, the quantum tunneling of magnetization (QTM) is partly or fully suppressed and the energy barriers increase to Ueff =128.6(5) K and tau0 =1.8*10(-8) s for 1, Ueff =214.7 K and tau0 =9.8*10(-9) s for 2, and Ueff =202.4 K and tau0 =1.5*10(-8) s for 3. The two pairs of largely negatively charged phenoxido oxygen atoms with short Dy?O bonds are positioned at opposite sides of the Dy(3+) ion, which thus creates a strong crystal field that stabilizes the axial MJ =+/ 15/2 doublet as the ground Kramers doublet. Although the compound with the Zn?OH2 motifs possesses the larger negative charges on the phenolate oxygen atoms, as confirmed by using DFT calculations, it exhibits the larger distortions of the DyO9 coordination polyhedron from ideal geometries and a smaller Ueff value. Ab initio calculations support the easy-axis anisotropy of the ground Kramers doublet and predict zero-field SMM behavior through Orbach and TA-QTM relaxations via the first excited Kramers doublet, which leads to large energy barriers. In accordance with the experimental results, ab initio calculations have also shown that, compared with water, the peripheral halide ligands coordinated to the Zn(2+) ions increase the barrier height when the distortions of the DyO9 have a negative effect. All the complexes exhibit metal-centered luminescence after excitation into the UV pi-pi* absorption band of ligand L(2-) at lambda=335 nm, which results in the appearance of the characteristic Dy(III) ((4) F9/2 ->(6) HJ/2 ; J=15/2, 13/2) emission bands in the visible region. PMID- 26361253 TI - Design and Application of Rolling Circle Amplification for a Tumor-Specific Drug Carrier. AB - It is challenging to design rolling circle amplification (RCA) for tumor selective delivery of drugs. Here, we devise a doxorubicin nanocarrier composed of RCA products, cholesterol-DNA, and folate-DNA conjugates. RCA products, designed to contain tandem repeats of short hairpin DNA, employ the repeated sequences complementary to both DNA conjugates, and thus RCA products/cholesterol DNA/folate-DNA complexes, generated via sequential base pairing processes, acquire the amphiphilic properties that facilitate self-assembly into the highly condensed nanoparticles (RCA nanoparticles). Doxorubicin-loaded RCA nanoparticles, especially with high cargo capacity, release drugs to the environment with the aid of acidity and show selective cytotoxicity to cancer cells. Particularly, the condensed structures enable RCA nanoparticles to be resistant to nucleases in the blood. These results show that RCA nanoparticles have great potential as a doxorubicin carrier for targeted cancer therapy, and furthermore, our strategy provides an alternative tool to exploit RCA techniques on drug delivery systems. PMID- 26361254 TI - Douglas fir (pseudotsuga menziesii) plantlets responses to as, PB, and sb contaminated soils from former mines. AB - Phytoremediation of metalloids by conifers is not widely studied although they may be relevant for several contaminated sites, especially those located in cold areas and sometimes under dry climates. Here, seeds of Douglas fir were sown in greenhouse on three soils collected in two French former mines: a gold mine (soils L1 and L2) and a lead and silver mine (soil P). These soils are highly contaminated by Pb, As, and Sb at different concentrations. Plants were harvested after ten weeks. Growth parameters, primary metabolite content, and shoot and root ionomes were determined. Douglas firs grown on the soils L1 and P had a lower biomass than controls and a higher oxidation status whereas those grown on the soil L2 exhibited a more developed root system and only slight modifications of carbon and nitrogen nutrition. Based on trace element (TE) concentrations in shoots and roots and their translocation factor (TF), Douglas fir could be a relevant candidate for As phytoextraction (0.8 g. kg(-1) dry weight in shoots and a TF of 1.1) and may be used to phytostabilize Pb and Sb (8.8 g and 127 mg. kg( 1) in roots for Pb and Sb, respectively, and TF lower than 0.1). PMID- 26361255 TI - A Structure-Activity Analysis for Probing the Mechanism of Processive Double Stranded DNA Digestion by lambda Exonuclease Trimers. AB - lambda exonuclease (lambdaexo) is an ATP-independent 5'-to-3' exonuclease that binds to double-stranded DNA (dsDNA) ends and processively digests the 5'-strand into mononucleotides. The crystal structure of lambdaexo revealed that the enzyme forms a ring-shaped homotrimer with a central funnel-shaped channel for tracking along the DNA. On the basis of this structure, it was proposed that dsDNA enters the open end of the channel, the 5'-strand is digested at one of the three active sites, and the 3'-strand passes through the narrow end of the channel to emerge out the back. This model was largely confirmed by the structure of the lambdaexo DNA complex, which further revealed that the enzyme unwinds the DNA by 2 bp prior to cleavage, to thread the 5'-end of the DNA into the active site. On the basis of this structure, an "electrostatic ratchet" model was proposed, in which the enzyme uses a hydrophobic wedge to insert into the base pairs to unwind the DNA, a two-metal mechanism for nucleotide hydrolysis, a positively charged pocket to bind to the terminal 5'-phosphate generated after each round of cleavage, and an arginine residue (Arg-45) to bind to the minor groove of the downstream end of the DNA. To test this model, in this study we have determined the effects of 11 structure-based mutations in lambdaexo on DNA binding and exonuclease activities in vitro, and on DNA recombination in vivo. The results are largely consistent with the model for the mechanism that was proposed on the basis of the structure and provide new insights into the roles of particular residues of the protein in promoting the reaction. In particular, a key role for Arg-45 in DNA binding is revealed. PMID- 26361256 TI - Autoimmune Thyroid Diseases. PMID- 26361257 TI - The Pathogenesis of Hashimoto's Thyroiditis: Further Developments in our Understanding. AB - Hashimoto's thyroiditis (HT) is part of a spectrum of thyroid autoimmune conditions and this review provides an update on the latest developments in the field. HT has a genetic predisposition with a number of immune-related and thyroid-specific genes conferring disease susceptibility. However, disentangling genes with protective and predisposing effect is a complex process that requires further work. The recent increase in the incidence of HT implicates environmental factors in disease pathogenesis including improved hygiene, increased dietary iodine intake, new treatment modalities and chemical agents. Additional unmodifiable predisposing factors include stress, climate, age and gender. Both cellular and humoral immunity play a role in HT pathogenesis. Defects in T regulatory cells and increased activation of follicular helper T cells may have a role in disease initiation/perpetuation. Infiltrating lymphocytes can be directly cytotoxic to thyroid follicular cells (TFC) or may affect cell viability/function indirectly through cytokine production, which alters TFC integrity and modulates their metabolic and immune function. Thyroid peroxidase and thyroglobulin antibodies are present in the majority of HT patients and help with management decisions. Antibodies against the sodium iodide symporter and pendrin are present in a minority with little known about their clinical relevance. In addition to immune cells, recent work has identified DNA fragments, generated following cell death, and micro RNA as potential factors in HT pathogenesis. Despite the large number of studies, the mechanistic pathways in HT are still not fully understood and further work is required to enhance our knowledge and identify novel preventative and therapeutic clinical targets. PMID- 26361258 TI - The Role of Iodine and Selenium in Autoimmune Thyroiditis. AB - Iodine and selenium (Se) are both essential elements to thyroid hormone economy, while they represent key players in the development of autoimmune thyroiditis.Chronic high iodine intake has been associated in various studies with increased frequency of autoimmune thyroiditis. In susceptible individuals, iodine excess increases intra-thyroid infiltrating Th17 cells and inhibits T regulatory (TREG) cells development, while it triggers an abnormal expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in thyrocytes, thus inducing apoptosis and parenchymal destruction. As was shown in a mouse model, high iodine supply leads to changes in the immunogenicity of the thyroglobulin molecule, upregulation of vascular intercellular adhesion molecule 1 (ICAM-1), and reactive oxygen species (ROS) generation in the thyrocytes. Serum Se levels were found decreased in Hashimoto thyroiditis and especially in Graves' disease as well as in thyroid-associated ophthalmopathy patients, the levels being related to the pathogenesis and outcome. Selenium is strongly involved, via the variable selenoproteins, in antioxidant, redox, and anti-inflammatory processes. Selenium enhances CD4+/CD25 FOXP3 and T regulatory cells activity while suppressing cytokine secretion, thus preventing apoptosis of the follicular cells and providing protection from thyroiditis. Selenium supplementation may be useful in autoimmune thyroid diseases, though, while usually well-tolerated, it should not be universally recommended, and it is also likely to be helpful for those with low Se status and autoimmunity. Broadly speaking, the achievement and maintenance of "selenostasis" as well as adequate urinary iodine excretion are mandatory to control disease, while, putatively, they may additionally be critical to preventing disease. PMID- 26361259 TI - Graves' Disease Mechanisms: The Role of Stimulating, Blocking, and Cleavage Region TSH Receptor Antibodies. AB - The immunologic processes involved in Graves' disease (GD) have one unique characteristic--the autoantibodies to the TSH receptor (TSHR)--which have both linear and conformational epitopes. Three types of TSHR antibodies (stimulating, blocking, and cleavage) with different functional capabilities have been described in GD patients, which induce different signaling effects varying from thyroid cell proliferation to thyroid cell death. The establishment of animal models of GD by TSHR antibody transfer or by immunization with TSHR antigen has confirmed its pathogenic role and, therefore, GD is the result of a breakdown in TSHR tolerance. Here we review some of the characteristics of TSHR antibodies with a special emphasis on new developments in our understanding of what were previously called "neutral" antibodies and which we now characterize as autoantibodies to the "cleavage" region of the TSHR ectodomain. PMID- 26361260 TI - Mechanisms of Action of TSHR Autoantibodies. AB - The availability of human monoclonal antibodies (MAbs) to the TSHR has enabled major advances in our understanding of how TSHR autoantibodies interact with the receptor. These advances include determination of the crystal structures of the TSHR LRD in complex with a stimulating autoantibody (M22) and with a blocking type autoantibody (K1-70). The high affinity of MAbs for the TSHR makes them particularly suitable for use as ligands in assays for patient serum TSHR autoantibodies. Also, M22 and K1-70 are effective at low concentrations in vivo as TSHR agonists and antagonists respectively. K1-70 has important potential in the treatment of the hyperthyroidism of Graves' disease and Graves' ophthalmopathy. Small molecule TSHR antagonists described to date do not appear to have the potency and/or specificity shown by K1-70. New models of the TSHR ECD in complex with various ligands have been built. These models suggest that initial binding of TSH to the TSHR causes a conformational change in the hormone. This opens a positively charged pocket in receptor-bound TSH which attracts the negatively charged sulphated tyrosine 385 on the hinge region of the receptor. The ensuing movement of the receptor's hinge region may then cause activation. Similar activation mechanisms seem to take place in the case of FSH and the FSHR and LH and the LHR. However, stimulating TSHR autoantibodies do not appear to activate the TSHR in the same way as TSH. PMID- 26361261 TI - Genetics of Graves' Disease: Special Focus on the Role of TSHR Gene. AB - As most autoimmune diseases, inherited predisposition to Graves' disease (GD) is polygenic with the main contributory genes being located in the HLA region. Also, as in other autoimmune diseases, family linkage, candidate gene association, and GWAS studies have identified an expanding number of predisposing genes (CTLA4, CD40, PTPN22...) and 2 of them, TG and TSHR, are thyroid specific. In spite of this expanding number of associated genes, it has been estimated that all together they account for only a 20% of the heritability of GD. TSHR is of special interest as it codes for the target of TSHR stimulating antibodies (TSAbs), which are unequivocally pathogenic and an exception in autoimmunity by being stimulating rather than neutral, blocking, or cytotoxic. This is surprising because the generation of stimulating TSHR antibodies by immunisation of laboratory animals has been remarkably difficult, suggesting an underlying mechanism that favours stimulating over neutral or blocking anti-TSHR antibodies must be operating in GD patients. Besides, after HLA, TSHR is the gene most tightly associated to GD. The TSHR polymorphisms conferring susceptibility are located in the unusually large intron 1. Two mechanisms have been already put forward to explain its association with GD. According to one, the risk alleles determine an increase in the expression of TSHR mRNA splice variants that code for a soluble form of the receptor. The wider distribution of soluble TSHR would favour its immunogenicity and the development of an autoimmune response to it. It does not explain why it becomes immunogenic, as immunogenicity and distribution are not necessarily connected, nor why the immune response focus to the production of stimulating antibodies. According to the second mechanism proposed, the risk alleles determine a lower TSHR expression in the thymus and this would favour the escape of more TSHR reactive T cells, that is, central tolerance failure. The unexpected finding that thymocytes express TSHR and that TSAbs stimulate them lead to postulate that this would accelerate their egress from the thymus and a less efficient deletion of the TSHR self-reactive T cells. It can be envisaged that these autoreactive T cells may enhance the production of TSHR-Abs in the germinal centres of the thyroid draining lymph nodes, especially of those capable of further stimulating the egress of autoreactive T cells from the thymus. This mechanism, which does not exclude the former, provides and insight of the way in which TSAbs are favoured over neutral or blocking antibodies. Finally this would explain the frequent finding of thymic hyperplasia in GD patients. PMID- 26361262 TI - Current Insights into the Pathogenesis of Graves' Ophthalmopathy. AB - Environmental, genetic, and immune factors are at play in the development of the variable clinical manifestations of Graves' ophthalmopathy (GO). Among the environmental contributions, smoking is the risk factor most consistently linked to the development or worsening of the disease. The close temporal relationship between the diagnoses of Graves' hyperthyroidism and GO have long suggested that these 2 autoimmune conditions may share pathophysiologic features. The finding that the thyrotropin receptor (TSHR) is expressed in orbital fibroblasts, the target cells in GO, supported the notion of a common autoantigen. Both cellular and humeral immunity directed against TSHR expressed on orbital fibroblasts likely initiate the disease process. Activation of helper T cells recognizing TSHR peptides and ligation of TSHR by TRAb lead to the secretion of inflammatory cytokines and chemokines, and enhanced hyaluronic acid (HA) production and adipogenesis. The resulting connective tissue remodeling results in varying degrees extraocular muscle enlargement and orbital fat expansion. A subset of orbital fibroblasts express CD34, are bone-marrow derived, and circulate as fibrocytes that infiltrate connective tissues at sites of injury or inflammation. As these express high levels of TSHR and are capable of producing copious cytokines and chemokines, they may represent an orbital fibroblast population that plays a central role in GO development. In addition to TSHR, orbital fibroblasts from patients with GO express high levels of IGF-1R. Recent studies suggest that these receptors engage in cross-talk induced by TSHR ligation to synergistically enhance TSHR signaling, HA production, and the secretion of inflammatory mediators. PMID- 26361263 TI - Medical Treatment of Graves' Orbitopathy. AB - The medical treatment of Graves' orbitopathy (GO) is usually reserved to moderate to severe disease. Steroids have been widely employed and possess anti inflammatory activity, but about 20-30% of patients are not responsive and about 20% present with disease recurrence. Immunosuppressive therapy alternative to corticosteroids may target the different antigens involved in pathogenic mechanisms of GO. Some have already been employed in clinical studies and showed interesting results, although the lack of randomized and controlled trials suggests caution for their use in clinical practice. Potential targets for therapy in GO are the TSH receptor and the IGF-1 receptor on the fibroblasts, inflammatory cytokines, B and T cells. Most promising results are obtained by interacting with the PIK3/mTORC1 signaling cascades for adipogenesis and the anti IGF-1R with the monoclonal antibody teprotumumab. A recent open study has shown that tocilizumab, an anti-sIL-6R antibody, inactivates GO. Consistent reports on the efficacy of rituximab have recently been challenged by randomized controlled trials. Clinical practice will greatly benefit from the use of disease modifying agents in GO, as compared to steroids, currently standard treatment for GO. Among these, rituximab may be useful, especially in patients resistant to steroid or with contraindications to steroids. However, larger randomized controlled trials are needed for definitive data on the potential disease-modifying role of rituximab in GO. Direct targeting of the orbital fibroblast via immunosuppression or nonimmunosuppressive drugs is emerging as a promising alternative. PMID- 26361264 TI - Higher order influences on evaluative priming: Processing styles moderate congruity effects. AB - A growing body of research challenges the automaticity of evaluative priming (EP). The present research adds to this literature by suggesting that EP is sensitive to processing styles. We relied on previous research showing that EP is determined by the extent to which the prime and the target events on a given trial are processed as a unified compound. Here, we further hypothesised that processing styles encouraging the inclusion of the prime to the target episode support congruity effects, whereas processing styles that enhance the exclusion of the prime from the target episode interrupt (or reverse) these effects. In Experiment 1, a preceding similarity search task produced a congruity effect, whereas a dissimilarity search task eliminated and (non-significantly) reversed this effect. In Experiments 2 and 3, we replicated and extended these findings using a global/local processing manipulation. Overall, these findings confirm that EP is flexible, open to top-down influences and strategic regulation. PMID- 26361266 TI - A General Method for Synthesis of Unclosed Cryptands via H-Bond Templated Macrocyclization and Subsequent Mild Postfunctionalization. AB - A practical four-step synthesis of a model 26-membered N-Boc-protected macrocycle, starting from commercially available and inexpensive materials, is reported. The crucial macrocyclization step does not require high-dilution conditions and is completed in a short time (8 h). The high yield of macrocyclization (61%) is achieved owing to templation by intramolecular H-bonds and a chloride anion, which both help to adopt a favorable folded conformation of the open-chain intermediate. Finally, mild, selective, and efficient incorporation of intraannular amide function leading to five diversely functionalized unclosed cryptands (UCs) is described. PMID- 26361265 TI - Regaining familiarity with own body after treatment for operable lung cancer - a qualitative longitudinal exploration. AB - Little is known about the experiences of operable lung cancer patients during treatment in a clinical setting based on fast-track surgery. The study aimed to explore (1) the embodied meaning of illness in patients with operable lung cancer during treatment to 4 months after surgery and (2) patterns of change over time that may affect the patients' daily lives. Twenty patients referred for lung cancer surgery were interviewed three times, corresponding to potential critical transition points following surgery: hospitalisation; hospital-to-home transition; and resumption of daily life activities. Data collection, analysis and interpretation followed a phenomenological hermeneutical approach inspired by Ricoeur and the theoretical framework was grounded in Merleau-Ponty's phenomenology of perception. The findings reveal the process patients went through in regaining familiarity with their own body after lung cancer treatment. Through the post-operative trajectory the patients' resumption of daily activities involved adjusting to a new awareness of everyday life, physical restrictions and their perception of themselves. The findings are expressed in four sub-themes: (1) perceptions of embodied alterations; (2) transformation of embodied structures in the transition from hospital to home was unexpectedly challenging; (3) embodied perceptions of the intersubjective world; and (4) transforming embodied disruptions into bodily awareness. Patients experienced a smooth treatment trajectory regarding physical consequences of illness and treatment which might be due to the fast-track surgery. Clinicians should be aware of patients' experiences of illness to facilitate patient reconstitution of own identity. PMID- 26361267 TI - Development of a Web-Based Self-management Intervention for Intermittent Urinary Catheter Users With Spinal Cord Injury. AB - While Web-based interventions have proliferated recently, information in the literature is often lacking about how the intervention was developed. In response to that gap, this is a report of the development of a Web-based self-management intervention for intermittent urinary catheter users and pretesting with four adults with spinal cord injury living in the community. Two Web sites were created, one for recruitment and the other for the intervention itself. The intervention involved developing new Web-based technology, including an interactive urinary diary (with fluid intake/urine output and a journal), extensive catheter products information, three intervention nurse phone call consultations, and user-community discussion forums. Study participants completed an online survey and were interviewed twice about the enrollment process and their perceptions of their involvement in the intervention. Suggestions from the pretesting participants were used to revise the Web site applications prior to the next stage of research (a feasibility study). Numerous recommendations and comments were received related to content, interactivity of components, and usability. This article provides a description of how the Web sites were developed (including the technology and software programs used), issues encountered and what was done to address them, and how the Web-based intervention was modified for improvements. PMID- 26361268 TI - Use of Simulation to Study Nurses' Acceptance and Nonacceptance of Clinical Decision Support Suggestions. AB - Our long-term goal was to ensure nurse clinical decision support works as intended before full deployment in clinical practice. As part of a broader effort, this pilot project explored factors influencing acceptance/nonacceptance of eight clinical decision support suggestions displayed in an electronic health record-based nursing plan of care software prototype. A diverse sample of 21 nurses participated in this high-fidelity clinical simulation experience and completed a questionnaire to assess reasons for accepting/not accepting the clinical decision support suggestions. Of 168 total suggestions displayed during the experiment (eight for each of the 21 nurses), 123 (73.2%) were accepted, and 45 (26.8%) were not accepted. The mode number of acceptances by nurses was seven of eight, with only two of 21 nurses accepting all. The main reason for clinical decision support acceptance was the nurse's belief that the suggestions were good for the patient (100%), with other features providing secondary reinforcement. Reasons for nonacceptance were less clear, with fewer than half of the subjects indicating low confidence in the evidence. This study provides preliminary evidence that high-quality simulation and targeted questionnaires about specific clinical decision support selections offer a cost-effective means for testing before full deployment in clinical practice. PMID- 26361269 TI - Counseling, screening, and therapy for newly-diagnosed HIV patients. AB - Newer testing methods, simplified treatment options, and advances in prevention have changed the way HIV is diagnosed and managed. This article reviews issues relevant for primary care clinicians and highlights the latest advances in HIV care and prevention. In addition, considerations for special populations are highlighted. PMID- 26361271 TI - Concentration measurement of yeast suspensions using high frequency ultrasound backscattering. AB - This work proposes the use of an ultrasound based technique to measure the concentration of yeasts in liquid suspension. This measurement was achieved by the detection and quantification of ultrasonic echoes backscattered by the cells. More specifically, the technique was applied to the detection and quantification of Saccharomyces cerevisiae. A theoretical approach was proposed to get the average density and sound speed of the yeasts, which were found to be 1116 kg/m(3) and 1679 m/s, respectively. These parameters were needed to model the waves backscattered by each single cell. A pulse-echo arrangement working around 50 MHz, being able to detect echoes from single yeasts was used to characterize experimentally yeast solutions from 10(2) to 10(7)cells/ml. The Non-negative Matrix Factorization denoising technique was applied for data analysis. This technique required a previous learning of the spectral patterns of the echoes reflected from yeasts in solution and the base noise from the liquid medium. Comparison between pulse correlation (without denoising) and theoretical and experimental pattern learning was made to select the best signal processing. A linear relation between ultrasound output and concentration was obtained with correlation coefficient R(2)=0.996 for the experimental learning. Concentrations from 10(4) to 10(7)cells/ml were detected above the base noise. These results show the viability of using the ultrasound backscattering technique to detect yeasts and measure their concentration in liquid cultures, improving the sensitivity obtained using spectrophotometric methods by one order of magnitude. PMID- 26361270 TI - Association of Acroosteolysis With Enhanced Osteoclastogenesis and Higher Blood Levels of Vascular Endothelial Growth Factor in Systemic Sclerosis. AB - OBJECTIVE: Bone resorption of distal phalanges, or acroosteolysis (AO), can develop in patients with systemic sclerosis (SSc), causing pain and functional limitation. This study was undertaken to investigate whether AO may be associated with abnormal osteoclastogenesis in SSc patients and whether hypoxia may be involved in this process. METHODS: Peripheral blood mononuclear cells (PBMCs) obtained from 26 SSc patients (11 with AO and 15 without AO) and 14 healthy controls were cultured in the presence of RANKL and macrophage colony-stimulating factor for 9 days. Tartrate-resistant acid phosphatase-positive multinucleated giant cells (MGCs) containing 3 or more nuclei were counted as osteoclasts. Plasma levels and effects of vascular endothelial growth factor (VEGF) on osteoclast formation were evaluated. RESULTS: SSc patients with AO formed significantly more osteoclasts after 9 days than did patients without AO (mean +/ SD 142.4 +/- 67.0 versus 27.2 +/- 17.6 MGCs/well; P < 0.001) or healthy controls (mean +/- SD 18.7 +/- 27.0 MGCs/well; P < 0.001). No significant difference in osteoclast formation was noted between the patients without AO and healthy controls. Plasma levels of VEGF were higher in SSc patients with AO compared to those without (mean +/- SD 142.4 +/- 69.6 pg/ml versus 88.1 +/- 38.2 pg/ml; P < 0.005) or healthy controls (54.2 +/- 24.6 pg/ml; P = 0.018). Priming with VEGF-A for 24 hours significantly increased osteoclast generation by 5.3 +/- 1.9 fold (P = 0.0018). The radiographic extent of AO was associated with increased osteoclast formation (Spearman's rho = 0.741, P = 0.01). CONCLUSION: Our findings indicate that increased osteoclast formation and higher VEGF levels may contribute to AO in SSc patients. Further studies are needed to elucidate whether targeting osteoclastogenesis may provide a specific therapeutic option for SSc-associated AO. PMID- 26361274 TI - Low-Index ZnO Crystal Plane-Specific Binding Behavior of Whole Immunoglobulin G Proteins. AB - Crystallographic surface-resolved examination of protein-ZnO interactions can greatly enhance the fundamental understanding of protein adsorption on these technologically important solid surfaces which, in turn, will be tremendously valuable for the emerging applications of ZnO-based biomaterials and biosensors. We examine experimentally and via computer simulations the intriguing differences in the adsorption preferences and binding behavior of whole immunoglobulin G (IgG) proteins to various, low-index ZnO crystal surfaces at the individual biomolecule level. By performing direct atomic force microscopy imaging, we determine that IgG predominantly binds to the ZnO plane of (1010) relative to the other three low-index planes of (0001), (0001), and (1120). This phenomenon is highly unusual, particularly considering the fact that the average binding energy of amino acids (AAs) on the ZnO (0001) facet is higher than that on the (1010) plane. In conjunction with combined Monte Carlo-molecular dynamics simulations, we further explain the possible origins of our unusual experimental findings with critical factors such as the specific spatial locations of strongly binding AAs in the protein and their spatial distributions on the exterior surface of the protein. PMID- 26361272 TI - Lymphopoiesis in transgenic mice over-expressing Artemis. AB - Artemis is a factor of the non-homologous end joining pathway involved in DNA double-strand break repair that has a critical role in V(D)J recombination. Mutations in DCLRE1C/ARTEMIS gene result in radiosensitive severe combined immunodeficiency in humans owing to a lack of mature T and B cells. Given the known drawbacks of allogeneic hematopoietic stem cell transplantation (HSCT), gene therapy appears as a promising alternative for these patients. However, the safety of an unregulated expression of Artemis has to be established. We developed a transgenic mouse model expressing human Artemis under the control of the strong CMV early enhancer/chicken beta actin promoter through knock-in at the ROSA26 locus to analyze this issue. Transgenic mice present a normal development, maturation and function of T and B cells with no signs of lymphopoietic malignancies for up to 15 months. These results suggest that the over-expression of Artemis in mice (up to 40 times) has no deleterious effects in early and mature lymphoid cells and support the safety of gene therapy as a possible curative treatment for Artemis-deficient patients. PMID- 26361273 TI - Hyaluronic acid pretreatment for Sendai virus-mediated cochlear gene transfer. AB - Gene therapy with viral vectors is one of the most promising strategies for sensorineural hearing loss. However, safe and effective administration of the viral vector into cochlear tissue is difficult because of the anatomical isolation of the cochlea. We investigated the efficiency and safety of round window membrane (RWM) application of Sendai virus, one of the most promising non genotoxic vectors, after pretreatment with hyaluronic acid (HA) on the RWM to promote efficient viral translocation into the cochlea. Sendai virus expressing the green fluorescent protein reporter gene was detected throughout cochlear tissues following application combined with HA pretreatment. Quantitative analysis revealed that maximum expression was reached 3 days after treatment. The efficiency of transgene expression was several 100-fold greater with HA pretreatment than that without. Furthermore, unlike the conventional intracochlear delivery methods, this approach did not cause hearing loss. These findings reveal the potential utility of gene therapy with Sendai virus and HA for treatment of sensorineural hearing loss. PMID- 26361275 TI - Gamma Knife surgery for patients with facial nerve schwannomas: a multiinstitutional retrospective study in Japan. AB - OBJECTIVE: The aim of this study was to explore the efficacy and safety of stereotactic radiosurgery for patients with facial nerve schwannomas (FNSs). METHODS: This study was a multiinstitutional retrospective analysis of 42 patients with FNSs treated with Gamma Knife surgery (GKS) at 1 of 10 medical centers of the Japan Leksell Gamma Knife Society (JLGK1301). The median age of the patients was 50 years. Twenty-nine patients underwent GKS as the initial treatment, and 13 patients had previously undergone surgery. At the time of the GKS, 33 (79%) patients had some degree of facial palsy, and 21 (50%) did not retain serviceable hearing. Thirty-five (83%) tumors were solid, and 7 (17%) had cystic components. The median tumor volume was 2.5 cm(3), and the median prescription dose to the tumor margin was 12 Gy. RESULTS: The median follow-up period was 48 months. The last follow-up images showed partial remission in 23 patients and stable tumors in 19 patients. Only 1 patient experienced tumor progression at 60 months, but repeat GKS led to tumor shrinkage. The actuarial 3- and 5-year progression-free survival rates were 100% and 92%, respectively. During the follow-up period, 8 patients presented with newly developed or worsened preexisting facial palsy. The condition was transient in 3 of these patients. At the last clinical follow-up, facial nerve function improved in 8 (19%) patients, remained stable in 29 (69%), and worsened in 5 (12%; House Brackmann Grade III in 4 patients, Grade IV in 1 patient). With respect to hearing function, 18 (90%) of 20 evaluated patients with a pure tone average of <= 50 dB before treatment retained serviceable hearing. CONCLUSIONS: GKS is a safe and effective treatment option for patients with either primary or residual FNSs. All patients, including 1 patient who required repeat GKS, achieved good tumor control at the last follow-up. The incidence of newly developed or worsened preexisting facial palsy was 12% at the last clinical follow-up. In addition, the risk of hearing deterioration as an adverse effect of radiation was low. These results suggest that GKS is a safe alternative to resection. PMID- 26361276 TI - Comparative analysis of outcomes following craniotomy and expanded endoscopic endonasal transsphenoidal resection of craniopharyngioma and related tumors: a single-institution study. AB - OBJECTIVE: Craniopharyngiomas and similar midline suprasellar tumors have traditionally been resected via transcranial approaches. More recently, expanded endoscopic endonasal transsphenoidal approaches have gained interest. Surgeons have advocated for both approaches, and at present there is no consensus whether one approach is superior to the other. The authors therefore compared surgical outcomes between craniotomy and endoscopic endonasal transsphenoidal surgery (EETS) for suprasellar tumors treated at their institution. METHODS: A retrospective review of patients undergoing resection of suprasellar lesions at Cedars-Sinai Medical Center between 2000 and 2013 was performed. Patients harboring suspected craniopharyngioma were selected for extensive review. Other pathologies or predominantly intrasellar masses were excluded. Cases were separated into 2 groups, based on the surgical approach taken. One group underwent EETS and the other cohort underwent craniotomy. Patient demographic data, presenting symptoms, and previous therapies were tabulated. Preoperative and postoperative tumor volume was calculated for each case based on MRI. Student t-test and the chi-square test were used to evaluate differences in patient demographics, tumor characteristics, and outcomes between the 2 cohorts. To assess for selection bias, 3 neurosurgeons who did not perform the surgeries reviewed the preoperative imaging studies and clinical data for each patient in blinded fashion and indicated his/her preferred approach. These data were subject to concordance analysis using Cohen's kappa test to determine if factors other than surgeon preference influenced the choice of surgical approach. RESULTS: Complete data were available for 53 surgeries; 19 cases were treated via EETS, and 34 were treated via craniotomy. Patient demographic data, preoperative symptoms, and tumor characteristics were similar between the 2 cohorts, except that fewer operations for recurrent tumor were observed in the craniotomy cohort compared with EETS (17.6% vs 42.1%, p = 0.05). The extent of resection was similar between the 2 groups (85.6% EETS vs 90.7% craniotomy, p = 0.77). An increased rate of cranial nerve injury was noted in the craniotomy group (0% EETS vs 23.5% craniotomy, p = 0.04). Postoperative CSF leak rate was higher in the EETS group (26.3% EETS vs 0% craniotomy, p = 0.004). The progression-free survival curves (log-rank p = 0.99) and recurrence rates (21.1% EETS vs 23.5% craniotomy, p = 1.00) were similar between the 2 groups. Concordance analysis of cases reviewed by 3 neurosurgeons indicated that individual surgeon preference was the only factor that determined surgical approach (kappa coefficient -0.039, p = 0.762) CONCLUSIONS: Surgical outcomes were similar for tumors resected via craniotomy or EETS, except that more CSF leaks occurred in the EETS cohort, whereas more neurological injuries occurred in the craniotomy cohort. Surgical approach appears to mostly reflect surgeon preference rather than specific tumor characteristics. These data support the view that EETS is a viable alternative to craniotomy, providing a similar extent of resection with less neurological injury. PMID- 26361277 TI - The cerebral isthmus: fiber tract anatomy, functional significance, and surgical considerations. AB - OBJECTIVE: The cerebral isthmus is the white matter area located between the periinsular sulcus and the lateral ventricle. Studies demonstrating the fiber tract and topographic anatomy of this entity are lacking in current neurosurgical literature. Hence, the authors' primary aim was to describe the microsurgical white matter anatomy of the cerebral isthmus by using the fiber dissection technique, and they discuss its functional significance. In addition, they sought to investigate its possible surgical utility in approaching lesions located in or adjacent to the lateral ventricle. METHODS: This study was divided into 2 parts and included 30 formalin-fixed cerebral hemispheres, 5 of which were injected with colored silicone. In the first part, 15 uncolored specimens underwent the Klinger's procedure and were dissected in a lateromedial direction at the level of the superior, inferior, and anterior isthmuses, and 10 were used for coronal and axial cuts. In the second part, the injected specimens were used to investigate the surgical significance of the superior isthmus in accessing the frontal horn of the lateral ventricle. RESULTS: The microsurgical anatomy of the anterior, superior, and inferior cerebral isthmuses was carefully studied and recorded both in terms of topographic and fiber tract anatomy. In addition, the potential role of the proximal part of the superior isthmus as an alternative safe surgical corridor to the anterior part of the lateral ventricle was investigated. CONCLUSIONS: Using the fiber dissection technique along with coronal and axial cuts in cadaveric brain specimens remains a cornerstone in the acquisition of thorough anatomical knowledge of narrow white matter areas such as the cerebral isthmus. The surgical significance of the superior isthmus in approaching the frontal horn of the lateral ventricle is stressed, but further studies must be carried out to elucidate its role in ventricular surgery. PMID- 26361278 TI - Causes of 30-day readmission after aneurysmal subarachnoid hemorrhage. AB - OBJECTIVE: Hospital readmission is a common but controversial quality measure increasingly used to influence hospital compensation in the US. The objective of this study was to evaluate the causes for 30-day hospital readmission following aneurysmal subarachnoid hemorrhage (SAH) to determine the appropriateness of this performance metric and to identify potential avenues for improved patient care. METHODS: The authors retrospectively reviewed the medical records of all patients who received surgical or endovascular treatment for aneurysmal SAH at Barnes Jewish Hospital between 2003 and 2013. Two senior faculty identified by consensus the primary medical/surgical diagnosis associated with readmission as well as the underlying causes of rehospitalization. RESULTS: Among 778 patients treated for aneurysmal SAH, 89 experienced a total of 97 readmission events, yielding a readmission rate of 11.4%. The median time from discharge to readmission was 9 days (interquartile range 3-17.5 days). Actual hydrocephalus or potential concern for hydrocephalus (e.g., headache) was the most frequent diagnosis (26/97, 26.8%), followed by infections (e.g., wound infection [5/97, 5.2%], urinary tract infection [3/97, 3.1%], and pneumonia [3/97, 3.1%]) and thromboembolic events (8/97, 8.2%). In most cases (75/97, 77.3%), we did not identify any treatment lapses contributing to readmission. The most common underlying causes for readmission were unavoidable development of SAH-related pathology (e.g., hydrocephalus; 36/97, 37.1%) and complications related to neurological impairment and immobility (e.g., thromboembolic event despite high-dose chemoprophylaxis; 21/97, 21.6%). The authors determined that 22/97 (22.7%) of the readmissions were likely preventable with alternative management. In these cases, insufficient outpatient medical care (for example, for hyponatremia; 16/97, 16.5%) was the most common shortcoming. CONCLUSIONS: Most readmissions after aneurysmal SAH relate to late consequences of hemorrhage, such as hydrocephalus, or medical complications secondary to severe neurological injury. Although a minority of readmissions may potentially be avoided with closer medical follow-up in the transitional care environment, readmission after SAH is an insensitive and likely inappropriate hospital performance metric. PMID- 26361279 TI - Carotid artery plaque assessment using quantitative expansive remodeling evaluation and MRI plaque signal intensity. AB - OBJECTIVE: Plaque characteristics and morphology are important indicators of plaque vulnerability. MRI-detected intraplaque hemorrhage has a great effect on plaque vulnerability. Expansive remodeling, which has been considered compensatory enlargement of the arterial wall in the progression of atherosclerosis, is one of the criteria of vulnerable plaque in the coronary circulation. The purpose of this study was risk stratification of carotid artery plaque through the evaluation of quantitative expansive remodeling and MRI plaque signal intensity. METHODS: Both preoperative carotid artery T1-weighted axial and long-axis MR images of 70 patients who underwent carotid endarterectomy (CEA) or carotid artery stenting (CAS) were studied. The expansive remodeling ratio (ERR) was calculated from the ratio of the linear diameter of the artery at the thickest segment of the plaque to the diameter of the artery on the long-axis image. Relative plaque signal intensity (rSI) was also calculated from the axial image, and the patients were grouped as follows: Group A = rSI >= 1.40 and ERR >= 1.66; Group B = rSI< 1.40 and ERR >= 1.66; Group C = rSI >= 1.40 and ERR < 1.66; and Group D = rSI < 1.40 and ERR < 1.66. Ischemic events within 6 months were retrospectively evaluated in each group. RESULTS: Of the 70 patients, 17 (74%) in Group A, 6 (43%) in Group B, 7 (44%) in Group C, and 6 (35%) in Group D had ischemic events. Ischemic events were significantly more common in Group A than in Group D (p = 0.01). CONCLUSIONS: In the present series of patients with carotid artery stenosis scheduled for CEA or CAS, patients with plaque with a high degree of expansion of the vessel and T1 high signal intensity were at higher risk of ischemic events. The combined assessment of plaque characterization with MRI and morphological evaluation using ERR might be useful in risk stratification for carotid lesions, which should be validated by a prospective, randomized study of asymptomatic patients. PMID- 26361280 TI - Factors associated with successful magnetic resonance-guided focused ultrasound treatment: efficiency of acoustic energy delivery through the skull. AB - OBJECTIVE: Magnetic resonance-guided focused ultrasound surgery (MRgFUS) was recently introduced as treatment for movement disorders such as essential tremor and advanced Parkinson's disease (PD). Although deep brain target lesions are successfully generated in most patients, the target area temperature fails to increase in some cases. The skull is one of the greatest barriers to ultrasonic energy transmission. The authors analyzed the skull-related factors that may have prevented an increase in target area temperatures in patients who underwent MRgFUS. METHODS: The authors retrospectively reviewed data from clinical trials that involved MRgFUS for essential tremor, idiopathic PD, and obsessive compulsive disorder. Data from 25 patients were included. The relationships between the maximal temperature during treatment and other factors, including sex, age, skull area of the sonication field, number of elements used, skull volume of the sonication field, and skull density ratio (SDR), were determined. RESULTS: Among the various factors, skull volume and SDR exhibited relationships with the maximum temperature. Skull volume was negatively correlated with maximal temperature (p = 0.023, r(2) = 0.206, y = 64.156 - 0.028x, whereas SDR was positively correlated with maximal temperature (p = 0.009, r(2) = 0.263, y = 49.643 + 11.832x). The other factors correlate with the maximal temperature, although some factors showed a tendency to correlate. CONCLUSIONS: Some skull related factors correlated with the maximal target area temperature. Although the number of patients in the present study was relatively small, the results offer information that could guide the selection of MRgFUS candidates. PMID- 26361281 TI - Time-delayed contrast-enhanced MRI improves detection of brain metastases and apparent treatment volumes. AB - OBJECTIVE: Contrast-enhanced MRI is the preeminent diagnostic test for brain metastasis (BM). Detection of BMs for stereotactic radiosurgery (SRS) planning may improve with a time delay following administration of a high-relaxivity agent for 1.5-T and 3-T imaging systems. Metastasis detection with time-delayed MRI was evaluated in this study. METHODS: Fifty-three volumetric MRI studies from 38 patients undergoing SRS for BMs were evaluated. All studies used 0.1-mmol/kg gadobenate dimeglumine (MultiHance; Bracco Diagnostics) immediately after injection, followed by 2 more axial T1-weighted sequences after 5-minute intervals (final image acquisition commenced 15 minutes after contrast injection). Two studies were motion limited and excluded. Two hundred eighty seven BMs were identified. The studies were randomized and examined separately by 3 radiologists, who were blinded to the temporal sequence. Each radiologist recorded the number of BMs detected per scan. A Wilcoxon signed-rank test compared BM numbers between scans. One radiologist determined the scan on which BMs were best defined. All confirmed, visible tumors were contoured using iPlan RT treatment planning software on each of the 3 MRI data sets. A linear mixed model was used to analyze volume changes. RESULTS: The interclass correlations for Scans 1, 2, and 3 were 0.7392, 0.7951, and 0.7290, respectively, demonstrating excellent interrater reliability. At least 1 new lesion was detected in the second scan as compared with the first in 35.3% of subjects (95% CI 22.4%-49.9%). The increase in BM numbers between Scans 1 and 2 ranged from 1 to 10. At least 1 new lesion was detected in the third scan as compared with the second in 21.6% of subjects (95% CI 11.3%-35.3%). The increase in BM numbers between Scans 2 and 3 ranged from 1 to 9. Between Scans 1 and 3, additional tumors were seen on 43.1% of scans (increase ranged from 1 to 14). The median increase in tumor number for all comparisons was 1. There was a significant increase in number of BMs detected from Scan 1 to Scan 2 (p < 0.0367) and from Scan 1 to Scan 3 (p < 0.0264). In 34 of the 51 subjects (66.7%), the radiologist selected the third scan as the one providing the clearest tumor definition. There was an average 25.4% increase in BM volume between Scans 1 and 2 (p < 0.0001) and a 9% increase in BM volume between Scans 2 and 3 (p = 0.0001). CONCLUSIONS: In patients who are being prepared for SRS of BMs, delayed MRI after contrast injection revealed more targets that needed treatment. In addition, apparent treatment volumes increased with a time delay. To avoid missing tumors that could be treated at the time of planned SRS and resultant "treatment failures," the authors recommend that postcontrast MR images be acquired between 10 and 15 minutes after injection in patients undergoing SRS for treatment of BMs. PMID- 26361282 TI - Donor-side morbidity after contralateral C-7 nerve transfer: results at a minimum of 6 months after surgery. AB - OBJECT Donor-side morbidity associated with contralateral C-7 (CC7) nerve transfer remains controversial. The purpose of this study was to evaluate functional deficits in the donor limb resulting from prespinal route CC7 nerve transfer. METHODS A total of 63 patients were included. Forty-one patients had undergone CC7 nerve transfer surgery at least 6 months previously and were assigned to one of 2 groups based on the duration of postoperative follow-up. Group 1 (n = 21) consisted of patients who had undergone surgery between 6 months and 2 years previously, and Group 2 (n = 20) consisted of patients who had undergone surgery more than 2 years previously. An additional 22 patients who underwent CC7 nerve transfer surgery later than those in Groups 1 and 2 were included as a control group (Group 3). Results of preoperative testing in these patients and postoperative testing in Groups 1 and 2 were compared. Testing included subjective assessments and objective examinations. An additional 3 patients had undergone surgery more than 6 months previously but had severe motor weakness and were therefore evaluated separately; these 3 patients were not included in any of the study groups. RESULTS The revised Short-Form McGill Pain Questionnaire (SF-MPQ-2) was the only subjective test that showed a significant difference between Group 3 and the other 2 groups, while no significant differences were found in objective sensory, motor, or dexterity outcomes. The interval from injury to surgery for patients with a normal SF-MPQ-2 score in Groups 1 and 2 was significantly less than for those with abnormal SF-MFQ-2 scores (2.4 +/- 1.1 months vs 4.6 +/- 2.9 months, p = 0.002). The 3 patients with obvious motor weakness showed a tendency to gradually recover. CONCLUSIONS Although some patients suffered from long-term sensory disturbances, resection of the C-7 nerve had little effect on the function of the donor limb. Shortening preoperative delay time can improve sensory recovery of the donor limb. PMID- 26361283 TI - Timing of the resumption of antithrombotic agents following surgical evacuation of chronic subdural hematomas: a retrospective cohort study. AB - OBJECTIVE: Antithrombosis (AT), defined here as either antiplatelets or anticoagulants, is a significant risk factor for the development of chronic subdural hematomas (cSDHs). Resuming AT following the evacuation of cSDH is a highly variable practice, with scant evidence in the literature for guidance. Here, a retrospective analysis of a cohort of patients from a single institution undergoing surgical drainage of cSDH was performed to evaluate postoperative complications and determine the optimal timing of the resumption of common antithrombotic agents. METHODS: This retrospective analysis was performed on 479 patients undergoing surgical evacuation of cSDH at St. Michael's Hospital over a 5-year period (2007-2012). The collected variables included the type of AT agent, indications for AT, timing and type of postoperative complications, and the restart intervals for the AT agents, when available. Postoperative complications were classified as major hemorrhages, minor hemorrhages, or thromboembolic events. RESULTS: Among all 479 study patients, 71 experienced major hemorrhage (14.8%), 110 experienced minor hemorrhage (23.0%), and 8 experienced thromboembolism (1.67%) postoperatively. Patients on any type of preoperative AT regimen were at a higher risk of major hemorrhage (19.0% vs 10.9%; OR 1.93; 95% CI 1.15-2.71; p = 0.014). The type of AT agent did not affect the frequency of any postoperative complications. Patients on any preoperative AT regimen experienced earlier postoperative major hemorrhages (mean 16.2 vs 26.5 days; p = 0.052) and thromboembolic events (mean 2.7 vs 51.5 days; p = 0.036) than those patients without a history of AT; the type of AT agent did not affect timing of complications. Patients who were restarted on any AT therapy postoperatively were at decreased risk of major rebleeding following resumption than those patients who were not restarted (OR 0.06; 95% CI 0.02-0.2; p < 0.01). CONCLUSIONS: Patients with a history of preoperative AT experienced thromboembolic complications significantly earlier than those patients without AT, which peaked at 3 days postoperatively with no increase in hemorrhage risk when AT was restarted. Cursory evidence is presented that shows resuming AT early following the surgical evacuation of cSDH at 3 days postoperatively may be safe. However, much larger prospective studies are required prior to providing any definitive recommendations regarding the optimal timing and method of resumption of individual agents. PMID- 26361284 TI - Comparison of the Dermatology Life Quality Index and the Children's Dermatology Life Quality Index in assessment of quality of life in patients with psoriasis aged 16-17 years. AB - BACKGROUND: Dermatology Life Quality Index (DLQI) and Children's Dermatology Life Quality Index (CDLQI) are widely used to assess quality of life (QoL) in adults (>= 16 years) and children (4-16 years) with psoriasis. In the age group 16-17 years, it is not known whether DLQI and CDLQI reflect QoL impairment in the same way. OBJECTIVES: To compare DLQI and CDLQI scores in patients with psoriasis aged 16-17 years. METHODS: Patients with psoriasis aged 16-17 years were asked to complete both the DLQI and CDLQI. RESULTS: Fifty-six patients were included. There was a high correlation between DLQI and CDLQI scores (r = 0.90, P < 0.001). The mean DLQI score (5.41 +/- 5.20) was lower than the mean CDLQI (6.61 +/- 5.74) (P < 0.001). The major part of this difference (?0.61) was caused by the low score regarding sexual difficulties in the DLQI (0.11 +/- 0.49) and the high score concerning sleep in the CDLQI (0.71 +/- 0.93). In addition, the question related to sports scored 0.34 in the DLQI but 0.86 in the CDLQI (?0.52). The question related to work/study in the DLQI scored lower than the question on school/holiday in the CDLQI (?0.41). CONCLUSIONS: In patients with psoriasis aged 16-17 years, DLQI and CDLQI scores closely correlate, but the mean DLQI score was lower than the mean CDLQI score. This was caused primarily by differences in the answers to questions regarding sexual difficulties and sleep. As the QoL impacts experienced by people aged 16-17 may differ from those experienced by children or adults, QoL measures designed for use in this age range may have advantages over both child- and adult-specific measures. PMID- 26361285 TI - How I Have Changed Over Time as a Psychotherapist. AB - Reflecting on my career as a psychotherapist has led me to consider 3 major areas that have affected the way I practice, namely, assimilative integration, the visions of reality, and brief psychodynamic therapy. Although starting out as a traditional psychoanalytic therapist, I became more integrative as I was exposed to other approaches and to patients with a variety of needs. As a result I developed a mode of integration, which I call assimilative. After applying the literary genres of tragedy, comedy, romance, and irony to psychoanalytic, behavioral, and humanistic psychotherapies, I found that they also could be used to describe any patient's multiple facets and psychological challenges. I demonstrate here how such visions helped in the treatment of a case of bipolar disorder. Upon recognizing the need for briefer forms of treatment, I developed an interest in conducting, conceptualizing, and researching brief psychodynamic therapy. I conclude the article by answering questions posed by the editors regarding how I have changed over time in conducting psychotherapy. PMID- 26361286 TI - Analysis of a waterborne disease model with socioeconomic classes. AB - Waterborne diseases such as cholera continue to pose serious public health problems in the world today. Transmission parameters can vary greatly with socioeconomic class (SEC) and the availability of clean water. We formulate a multi-patch waterborne disease model such that each patch represents a particular SEC with its own water source, allowing individuals to move between SECs. For a 2 SEC model, we investigate the conditions under which each SEC is responsible for driving a cholera outbreak. We determine the effect of SECs on disease transmission dynamics by comparing the basic reproduction number of the 2-SEC model to that of a homogeneous model that does not take SECs into account. We conclude by extending several results of the 2-SEC model to an n-SEC model. PMID- 26361287 TI - Unsteady non-Newtonian blood flow through a tapered overlapping stenosed catheterized vessel. AB - The unsteady flow characteristics of blood in a catheterized overlapping stenosed artery are analyzed in presence of body acceleration and magnetic field. The stenosed arterial segment is modeled as a rigid constricted tube. An improved shape of stenosis in the realm of the formulation of the arterial narrowing caused by atheroma is integrated in the present study. The catheter inside the artery is approximated by a thin rigid tube of small radius while the streaming blood in the artery is characterized by the Carreau model. Employing mild stenosis condition, the governing equation of the flow is derived which is then solving numerically using finite difference scheme. The variation of axial velocity, flow rate, resistance impendence and wall shear stress is shown graphically for various parameters of interest. The flow patterns illustrating the global behavior of blood are also presented. PMID- 26361288 TI - Bivariate spline solution of time dependent nonlinear PDE for a population density over irregular domains. AB - We study a time dependent partial differential equation (PDE) which arises from classic models in ecology involving logistic growth with Allee effect by introducing a discrete weak solution. Existence, uniqueness and stability of the discrete weak solutions are discussed. We use bivariate splines to approximate the discrete weak solution of the nonlinear PDE. A computational algorithm is designed to solve this PDE. A convergence analysis of the algorithm is presented. We present some simulations of population development over some irregular domains. Finally, we discuss applications in epidemiology and other ecological problems. PMID- 26361289 TI - Kirkpatrick's Evaluation of Educational Programs and its Relevance to Academic Radiology. PMID- 26361290 TI - How to be good. PMID- 26361291 TI - One avoidable death is one too many. PMID- 26361292 TI - Deployment to war and mental health consequences. PMID- 26361293 TI - A flying START for carers of people with dementia. PMID- 26361294 TI - Psychotropic drugs in low-income countries. PMID- 26361295 TI - Cardiometabolic health in young people with psychosis. PMID- 26361296 TI - A hip-hop state of mind. PMID- 26361297 TI - Resuscitating the biopsychosocial model. PMID- 26361298 TI - The diagnosis debate. PMID- 26361299 TI - The diagnosis debate. PMID- 26361300 TI - The diagnosis debate - Authors' reply. PMID- 26361301 TI - Mental health interventions in schools. PMID- 26361302 TI - Antipsychotic treatment discontinuation in clinical practice. PMID- 26361304 TI - Rethinking India's psychiatric care. PMID- 26361305 TI - Patrick McGorry. PMID- 26361306 TI - Cheerfulness and tranquility: gardens in the Victorian asylum. PMID- 26361307 TI - Scrutinised bodies: Egon Schiele and psychiatry. PMID- 26361308 TI - The burdensome image: Marlene Dumas. PMID- 26361309 TI - This is Where I Leave You: slapstick and slapdash. PMID- 26361310 TI - Practice nurse health checks for adults with intellectual disabilities: a cluster design, randomised controlled trial. AB - BACKGROUND: Adults with intellectual disabilities have substantial health inequalities and poor access to health care. We assessed whether practice nurse delivered health checks could improve the health of adults with intellectual disabilities compared with standard care. METHODS: In this cluster-design, single blind, randomised controlled trial, we included general practices in Scotland, UK. From June to December, 2011, we randomly assigned (1:1) these general practices to either health checks plus standard care (health-checks group), or standard care only (control group), and we recruited the patients from these practices. Randomisation was done with stratification by number of GPs per practice and number of registered patients with intellectual disabilities (<20 or >=20). Two research assistants were masked to allocation, and undertook the review of 9 month medical records and interviews. Participants and carers were not masked. The intervention was one health check designed especially for people with intellectual disabilities delivered by a practice nurse. The objective was improvement in health and health care 9 months after randomisation, and the primary outcome was the incidence of newly detected health needs being met by this timepoint. Whether needs were met was established by the investigators being masked to group allocation. The analysis was by intention to treat. This trial is registered with Current Controlled Trials, number ISRCTN43324841. FINDINGS: Between June 26 and Dec 20, 2011, we recruited 38 practices. 85 participants (from 16 practices) were randomly assigned to intervention and 67 (from 17 practices) to standard care; five of the identified practices did not supply any participants. 83 intervention and 66 standard care participants completed the trial. More newly detected health needs were met in the intervention group than in the control standard care group (median 1 [range 0-8], 76.4% met [SD 36.5] vs 2 [0-11], 72.6% met [35.4]; odds ratio [OR] 1.73 [95% CI 0.93-3.22], p=0.085), although this difference was not significant. Significantly more health monitoring needs were met in the intervention group than standard care (median 2 [0-20], 69.9% [SD 34.2] vs 2 [0-22], 56.8% [29.4], OR 2.38 [95% CI 1.31-4.32, p=0.0053]). The probability that health checks are cost effective was between 0.6 and 0.8, irrespective of the cost-effectiveness threshold level. Costs per patient were -L71.48 for health checks and -L20.56 for standard care. The difference (-L50.92) was not significant [95% CI -434 to 362]. No adverse events were attributable to the intervention. INTERPRETATION: Health checks given by practice nurses to adults with intellectual disabilities produced health-care improvements that were more conducive to longer-term health than standard care given to this population. The intervention dominated standard care, being both cheaper and more effective. Health-check programmes might therefore be indicated for adults with intellectual disabilities. FUNDING: Scottish Government Change Fund, NHS Greater Glasgow and Clyde Research and Development. PMID- 26361311 TI - Assessment of an incentivised scheme to provide annual health checks in primary care for adults with intellectual disability: a longitudinal cohort study. AB - BACKGROUND: People with intellectual disabilities (ID) have many comorbidities but experience inequities in access to health care. National Health Service England uses an opt-in incentive scheme to encourage annual health checks of patients with ID in primary care. We investigated whether the first 3 years of the programme had improved health care of people with ID. METHODS: We did a longitudinal cohort study that used data from The Health Improvement Network primary care database. We did multivariate logistic regression to assess associations between various characteristics and whether or not practices had opted in to the incentivised scheme. FINDINGS: We assessed data for 8692 patients from 222 incentivised practices and those for 918 patients in 48 non-incentivised practices. More blood tests (eg, total cholesterol, odds ratio [OR] 1.88, 95% CI 1.47-2.41, p<0.0001) general health measurements (eg, smoking status, 6.0, 4.10 8.79, p<0.0001), specific health assessments (eg, hearing, 24.0, 11.5-49.9, p<0.0001), and medication reviews (2.23, 1.68-2.97, p<0.0001) were done in incentivised than in non-incentivised practices, and more health action plans (6.15, 1.41-26.9, p=0.0156) and secondary care referrals (1.47, 1.05-2.05, p=0.0256) were made. Identification rates were higher in incentivised practices for thyroid disorder (OR 2.72, 95% CI 1.09-6.81, p=0.0323), gastrointestinal disorders (1.94, 1.03-3.65, p=0.0390), and obesity (2.49, 1.76-3.53, p<0.0001). INTERPRETATION: Targeted annual health checks for people with ID in primary care could reduce health inequities. FUNDING: National Institute for Health Research. PMID- 26361312 TI - Mental health consequences of overstretch in the UK Armed Forces, 2007-09: a population-based cohort study. AB - BACKGROUND: Concerns have been raised about the effect of tour length on the mental health of the UK armed forces. In 2007, we reported that cumulative length of deployment was associated with mental illness in military personnel. Our findings provided empirical evidence to support the UK advisory policy for tour length, known as the Harmony Guidelines. If fully implemented, these guidelines could aid prevention of mental illnesses. We aimed to reassess the association between cumulative length of deployment and number of deployments with mental illness in the UK forces. METHODS: Our analysis was based on data from a representative study of the military for UK regular personnel who had completed a questionnaire between Nov 2, 2007, and Sept 24, 2009, and were deployed in the 3 years before questionnaire completion. Study outcomes were presence of possible post-traumatic stress disorder (PTSD), psychological distress, multiple physical symptoms, alcohol misuse, problems at home during and after deployment, and relationship or family problems. The key independent factors were deployment for 13 months or more, and months and number of deployments in the past 3 years. FINDINGS: 8278 regulars responded to the questionnaire, of whom 3982 (48%) had been deployed in the 3 years before questionnaire completion. Deployment for 13 months or more decreased from 22% in March, 2005, (median March 8, 2005 [IQR Oct 10, 2004 to April 28, 2005]), to 12% in May, 2008, (May 17, 2008, [Feb 14, 2008, to Dec 5, 2008]). We noted an association between cumulative time deployed as a continuous variable and a score of 40 or more on the PTSD checklist (p=0.002), presence of psychological distress (p=0.018), and multiple physical symptoms (p=0.030; table 2). Furthermore, 13 months or more of deployment was associated with multiple physical symptoms (adjusted odds ratio [OR] 2.15, 95% CI 1.39 3.32), a PTSD checklist score of 40 or more (2.02, 1.31-3.12), and problems at home, but not a PTSD checklist score of 50 or more (1.50, 0.82-2.75), psychological distress 1.34, 0.98-1.85), or alcohol misuse (1.32, 0.97-1.80). Number of deployments was not associated with worse mental illness status or problems at home. INTERPRETATION: The Harmony Guidelines can prevent mental illness in the UK Armed Forces and, since 2006, their introduction has prevented personnel from being deployed for a longer period than recommended in the guidelines. Monitoring of cumulative length of deployment might reduce mental illness in the UK military. FUNDING: The UK Ministry of Defence. PMID- 26361313 TI - Long-term clinical and cost-effectiveness of psychological intervention for family carers of people with dementia: a single-blind, randomised, controlled trial. AB - BACKGROUND: Two-thirds of people with dementia live at home supported mainly by family carers. These carers frequently develop clinical depression or anxiety, which predicts care breakdown. We aimed to assess the clinical effectiveness (long-term reduction of depression and anxiety symptoms in family carers) and cost-effectiveness of a psychological intervention called START (STrAtegies for RelaTives). METHODS: We did a randomised, parallel-group trial with masked outcome assessments in three UK mental-health services and one neurological outpatient dementia service. We included self-identified family carers of people with dementia who had been referred in the previous year and gave support at least once per week to the person with dementia. We randomly assigned these carers, via an online computer-generated randomisation system from an independent clinical trials unit, to either START, an 8-session, manual-based coping intervention delivered by supervised psychology graduates, or treatment as usual (TAU). The primary long-term outcomes were affective symptoms (Hospital Anxiety and Depression Scale total score [HADS-T]) 2 years after randomisation and cost effectiveness (health and social care perspectives) over 24 months. Analysis was by intention to treat, excluding carers with data missing at both 12 and 24 months. This trial is registered ISCTRN70017938. FINDINGS: From November 4, 2009, to June 8, 2011, we recruited 260 carers. 173 carers were randomly assigned to START and 87 to TAU. Of these 260 participants, 209 (80%) were included in the clinical efficacy analysis (140 START, 69 TAU). At 24 months, compared with TAU the START group was significantly better for HADS-T (mean difference -2.58 points, 95% CI -4.26 to -0.90; p=0.003). The intervention is cost effective for both carers and patients (67% probability of cost-effectiveness at the L20 000 per QALY willingness-to-pay threshold, and 70% at the L30 000 threshold). INTERPRETATION: START is clinically effective, improving carer mood and anxiety levels for 2 years. Carers in the control TAU group were seven times more likely to have clinically significant depression than those receiving START. START is cost effective with respect to carer and patient outcomes, and National Institute for Health and Care Excellence (NICE) thresholds. The number of people with dementia is rapidly growing, and policy frameworks assume that their families will remain the frontline providers of (unpaid) support. This cost-neutral intervention, which substantially improves family-carers' mental health and quality of life, should therefore be widely available. FUNDING: National Institute for Health Research Health Technology Assessment programme 08/14/06. PMID- 26361314 TI - Changes in the adolescent brain and the pathophysiology of psychotic disorders. AB - Adolescence is a time of extensive neuroanatomical, functional, and chemical reorganisation of the brain which parallels substantial maturational changes in cognition and affect regulation. This period is characterised by stabilisation of synapses to diminish redundancy and increase efficiency of neural function, fine tuning of excitatory and inhibitory neurotransmitter systems, beginning of integration between late maturing and early maturing brain structures, and development of effective connections. In effect, these so-called moving parts create a state of dynamic change that might underlie adolescent behaviours. Imbalances or changes in timing of these developmental processes clearly increase the risk for psychiatric disorders. Genetic, environmental, and epigenetic factors that shape brain development and hormonal changes that affect stress reactivity could be reasons why some, but not all, adolescents are at a heightened risk of developing a psychopathological disorder. In this Series paper, we assess the neurobiology of the changing adolescent brain, implications of this knowledge, and future research in major psychiatric disorders, particularly for psychotic disorders. PMID- 26361315 TI - Cultures for mental health care of young people: an Australian blueprint for reform. AB - Mental ill health is now the most important health issue facing young people worldwide. It is the leading cause of disability in people aged 10-24 years, contributing 45% of the overall burden of disease in this age group. Despite their manifest need, young people have the lowest rates of access to mental health care, largely as a result of poor awareness and help-seeking, structural and cultural flaws within the existing care systems, and the failure of society to recognise the importance of this issue and invest in youth mental health. We outline the case for a specific youth mental health stream and describe the innovative service reforms in youth mental health in Australia, using them as an example of the processes that can guide the development and implementation of such a service stream. Early intervention with focus on the developmental period of greatest need and capacity to benefit, emerging adulthood, has the potential to greatly improve the mental health, wellbeing, productivity, and fulfilment of young people, and our wider society. PMID- 26361316 TI - The new life stage of emerging adulthood at ages 18-29 years: implications for mental health. AB - Since 1960 demographic trends towards longer time in education and late age to enter into marriage and of parenthood have led to the rise of a new life stage at ages 18-29 years, now widely known as emerging adulthood in developmental psychology. In this review we present some of the demographics of emerging adulthood in high-income countries with respect to the prevalence of tertiary education and the timing of parenthood. We examine the characteristics of emerging adulthood in several regions (with a focus on mental health implications) including distinctive features of emerging adulthood in the USA, unemployment in Europe, and a shift towards greater individualism in Japan. PMID- 26361317 TI - Teaching global mental health at home and abroad. PMID- 26361318 TI - A box of delights. PMID- 26361319 TI - Update on the approach of urinary tract infection in childhood. AB - OBJECTIVE: Urinary tract infection (UTI) is the most common bacterial infection in childhood. UTI may be the sentinel event for underlying renal abnormality. There are still many controversies regarding proper management of UTI. In this review article, the authors discuss recent recommendations for the diagnosis, treatment, prophylaxis, and imaging of UTI in childhood based on evidence, and when this is lacking, based on expert consensus. SOURCES: Data were obtained after a review of the literature and a search of Pubmed, Embase, Scopus, and Scielo. SUMMARY OF THE FINDINGS: In the first year of life, UTIs are more common in boys (3.7%) than in girls (2%). Signs and symptoms of UTI are very nonspecific, especially in neonates and during childhood; in many cases, fever is the only symptom. CONCLUSIONS: Clinical history and physical examination may suggest UTI, but confirmation should be made by urine culture, which must be performed before any antimicrobial agent is given. During childhood, the proper collection of urine is essential to avoid false-positive results. Prompt diagnosis and initiation of treatment is important to prevent long-term renal scarring. Febrile infants with UTIs should undergo renal and bladder ultrasonography. Intravenous antibacterial agents are recommended for neonates and young infants. The authors also advise exclusion of obstructive uropathies as soon as possible and later vesicoureteral reflux, if indicated. Prophylaxis should be considered for cases of high susceptibility to UTI and high risk of renal damage. PMID- 26361320 TI - Rhinacanthin-C, A Fat-Soluble Extract from Rhinacanthus nasutus, Modulates High Mobility Group Box 1-Related Neuro-Inflammation and Subarachnoid Hemorrhage Induced Brain Apoptosis in a Rat Model. AB - OBJECTIVE: High-mobility group box 1 (HMGB1) was shown to be a major extracellular mediator involved in relayed neuro-inflammation in animals after subarachnoid hemorrhage (SAH). It is of interest to examine the effect of rhinacanthin-C (RCT-C, C25H30O5) on pro-inflammatory cytokines/HMGB1 in an SAH related early brain injury model. METHODS: A rodent double SAH model was used. RCT-C was administered orally at 100, 200, and 400 MUmol/kg/day. Cerebral spinal fluid samples were obtained to assess interleukin (IL)-1beta, IL-6, IL-8, and tumor necrosis factor alpha using a real-time polymerase chain reaction. Basilar arteries were harvested and cerebral cortex was examined for HMGB1 mRNA and protein expression (western blot) and caspases (real-time polymerase chain reaction). An intrathecal injection of 1 ng of HMGB-1 recombinant protein was given in the 400 MUmol/kg/day RCT-C plus SAH groups. RESULTS: The levels of IL 1beta, IL-6, and tumor necrosis factor alpha mRNA were significantly increased in animals subject to SAH, compared with the healthy controls, but were absent in the RCT-C groups. Cleaved caspase-9a as well as HMGB-1 mRNA and protein were significantly reduced in the 400 MUmol/kg/day RCT-C treatment groups. Similarly, administration of RCT-C reduced HMGB-1 mRNA and protein expression (P <0.01). CONCLUSIONS: RCT-C exerts a neuroprotective effect by reducing cleaved caspase-3- and caspase-9a-related apoptosis. Decreased HMGB-1 mRNA and protein expression in the RCT-C groups corresponds to its anti-inflammatory effect. HMGB-1 recombinant protein administration impaired the neuroprotective and immunosuppressive effect of RCT-C. This finding lends credence that RCT-C modulates the HMGB-1-related pathway and attenuates brain apoptosis in the pathogenesis of SAH. PMID- 26361321 TI - Impact of Hyponatremia on Morbidity, Mortality, and Complications After Aneurysmal Subarachnoid Hemorrhage: A Systematic Review. AB - BACKGROUND: Hyponatremia is a common metabolic disturbance after aneurysmal subarachnoid hemorrhage (SAH), and it may worsen outcomes. This review aims to characterize the effect of hyponatremia on morbidity and mortality after SAH. OBJECTIVES: We sought to determine the prevalence of hyponatremia after SAH, including in subgroups, as well as its effect on mortality and certain outcome measures, including degree of disability and duration of hospitalization. METHODS: A search of terms "hyponatremia" and "subarachnoid hemorrhage" was performed on PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE. Studies were included if they reported prevalence of hyponatremia and if they discussed outcomes such as mortality, duration of stay, functional outcomes (e.g., Glasgow Outcomes Scale), or incidence of complications in patients with aneurysmal SAH. Two independent researchers assessed the titles and abstracts and reviewed articles for inclusion. RESULTS: Thirteen studies met inclusion criteria. The prevalence of at least mild hyponatremia was 859 of 2387 (36%) of patients. Hyponatremia was associated with vasospasm and duration of hospitalization, but it did not influence mortality. CONCLUSION: Hyponatremia is common after SAH, and there is evidence that it is associated with certain poorer outcomes. Larger, prospective studies are needed to assess these findings and provide further evidence. PMID- 26361322 TI - Fluctuations in Spinal Cord Perfusion During Adult Spinal Deformity Correction Identify Neurologic Changes: Proof of Concept. AB - INTRODUCTION: Adult spinal deformity (ASD) surgery carries the risk of spinal cord injury. Spinal cord ischemia is often implicated in the pathogenesis but has not been directly investigated. Here we present our index case as a proof of concept for a study evaluating the role of spinal cord perfusion (SCP) changes in ASD correction. METHODS: ASD surgery was performed in the usual fashion with the addition of 1) SCP monitoring, using laser Doppler probe fixated to the dura at the level of the pedicle subtraction osteotomy (PSO) and 2) intrathecal pressure monitoring, using a lumbar drain. Somatosensory evoked potential (SSEP) and motor evoked potential (MEP) were monitored throughout the case. RESULTS: An 84-year old male with kyphoscoliosis and progressive myelopathy causing diminished motor and sensory function was treated with T4 PSO and long segment reconstruction. At baseline, SSEP signals were detectable in all 4 extremities, MEP signals were present in the right foot only, intrathecal pressure was 4 mm Hg, and mean SCP was 21.2 perfusion units. The osteotomy was performed and reduced in 2 steps. After the first step of reduction, MEP signals appeared in the left leg and increased in amplitude in the right leg, and SCP simultaneously increased to 205.6. Further reduction led to MEP signal loss in both legs and decrease in SCP to 39.2. With partial reversal of the reduction, MEP signals returned in both legs and SCP improved to 76.0. Final reduction maneuvers were then performed in a delayed fashion before closure, with stable MEP signals and a final SCP of 42.9. SSEP signals, vital signs, and intrathecal pressure were stable throughout the case. Postoperatively the patient was neurologically stable. CONCLUSIONS: The present case provides the first direct evidence that fluctuations in SCP may contribute to neurologic changes during ASD surgery. Further investigation is under way to further elucidate the underlying mechanisms, with the ultimate goal of developing targeted strategies for spinal cord protection during these high risk cases. PMID- 26361323 TI - Neurosurgery Elective for Preclinical Medical Students: Early Exposure and Changing Attitudes. AB - OBJECTIVE: Exposure to surgical subspecialties is limited during the preclinical years of medical school. To offset this limitation, the authors created a neurosurgery elective for first- and second-year medical students. The objective was to provide each student with early exposure to neurosurgery by combining clinical experience with faculty discussions about the academic and personal realities of a career in neurosurgery. METHODS: From 2012 to 2013, the authors offered a neurosurgery elective course to first- and second-year medical students. Each class consisted of the following: 1) peer-reviewed article analysis; 2) student presentation; 3) faculty academic lecture; 4) faculty personal lecture with question and answer period. RESULTS: Thirty-five students were enrolled over a 2-year period. After completing the elective, students were more likely to: consider neurosurgery as a future career (P < 0.0001), perceive the personalities of attending physicians to be more collegial and friendly (P = 0.0002), perceive attending quality of life to be higher (P < 0.0001), and believe it was achievable to be a neurosurgeon and have a family (P < 0.0001). The elective did not alter students' perceived difficulty of training (P = 0.7105). CONCLUSIONS: The neurosurgery elective course significantly increased student knowledge across several areas and changed perceptions about collegiality, quality of life, and family-work balance, while not altering the students' views about the difficulty of training. Adopting a neurosurgery elective geared towards preclinical medical students can significantly change attitudes about the field of neurosurgery and has potential to increase interest in pursuing a career in neurosurgery. PMID- 26361324 TI - Paradoxical Radiographic Changes of Coflex Interspinous Device with Minimum 2 Year Follow-Up in Lumbar Spinal Stenosis. AB - OBJECTIVES: Studies have yet to investigate long-term radiologic changes in lumbar spinal stenosis patients treated with interspinous device (Coflex). This study aimed to evaluate which radiologic parameters change significantly after surgery with Coflex and identify which parameter most affects the radiologic outcome. METHODS: Of 101 patients with lumbar spinal stenosis treated by Coflex insertion on L4-5, the radiologic parameters of 30 patients were measured before and at least 2 years after surgery. On the basis of the development of bony erosion around Coflex, patients were divided into the erosion group (n = 14) or the nonerosion group (n = 16). RESULTS: The mean anterior disc height (ADH) and range of motion (ROM) were significantly decreased after surgery (15.161 mm vs. 13.788 mm and 9.63 degrees vs. 7.13 degrees ). The erosion group showed substantially higher values in preoperative ADH, postoperative posterior disc height (PDH), and intervertebral foramen height (6.52 mm vs. 8.05 mm; 5.80 mm vs. 8.03 mm; 19.20 mm vs. 21.06 mm). Postoperative ROM and ROM ratio were higher in the erosion group (5.95 degrees vs. 8.47 degrees and 0.659 vs. 0.938). However, only ADH showed a significant change in the erosion group after surgery (15.86 mm vs. 14.29 mm). On the contrary, ADH and PDH, as well as ROM, were significantly decreased in the nonerosion group (14.55 mm vs. 13.34 mm; 6.52 mm vs. 5.82 mm; 9.46 degrees vs. 5.95 degrees ). CONCLUSION: The preoperative state including relatively higher ADH, PDH, and larger ROM could induce erosion. The long-term preservation of disc height and ROM may also induce erosion. That reduction of most radiologic parameters seems to be natural after surgery, and insufficient reduction of disc height and ROM may induce adverse effects, which can increase the possibility of spinous process fracture or device malposition. PMID- 26361325 TI - Life-Threatening Cerebral Hematoma Owing to Aneurysm Rupture. AB - OBJECTIVE: To refine the surgical indications of surgery for life-threatening cerebral hematomas caused by aneurysm rupture, through the analysis of possible outcome predictors. METHODS: Forty-nine consecutive patients requiring prompt clot evacuation were retrospectively reviewed. In all cases, the hematoma was equal to or greater than 60 mL. The bleeding aneurysm was located on the middle cerebral artery in 26 cases, on the internal carotid artery in 10 cases, and on the anterior cerebral artery in 13 cases; four aneurysms were giant. Six patients underwent aneurysm coiling followed by clot removal, whereas 43 patients were managed by concomitant clot evacuation and aneurysm clipping. The main clinical and radiologic features, the management paths and the treatment modalities were correlated with the outcomes. A statistical analysis was conducted. RESULTS: Overall mortality was 32.6%, severe morbidity was 22.4% and 22 patients (44.8%) achieved favorable results. The short-term results were more significantly influenced by the radiological parameters than by the initial clinical conditions. The prognostic weight of the radiologic findings was partially lost for six-month results, whereby management factors gained in importance. CONCLUSIONS: The bleeding severity was strongly determinant for early mortality. However, if patients can survive the initial crucial phase, their chances of a favorable outcome are not negligible. Further improvement may be possible through better patient selection and the identification of nonsalvageable subjects. PMID- 26361326 TI - Mental and Physical Health Outcomes in Parents of Children with Burn Injuries as Compared with Matched Controls. AB - Pediatric burn injuries are common, and the stress of caring for them can affect caregivers' health. This study's objective was to examine the rates of common mental and physical disorders of parents of burn-injured children (cases) compared with matched controls (controls). This is a population-based study linking the Regional Pediatric burn registry with administrative health information. Pediatric burn cases were matched 1:5 with control children from the general population based on age, sex, and geographical location then parents identified. One thousand and twenty-six parental cases and 4858 controls were identified. International Classification of Disease codes were used to identify diagnoses of common mental and physical disorders. Using rates of disease 2 years before and 2 years after the date of burn, the changes in the relative rates of health outcomes were compared between the cases and the controls. The cases had higher rates of postinjury mental and physical illness compared with the matches. However, it was found that controls also had increased rates postindex date and additionally cases had increased rates of preinjury illnesses. There was no difference in the relative rates of illnesses between the groups from pre- to post-index date. The higher rate of illness in cases postinjury could be explained by preinjury illness, and similar rate increases in the control cohort. Evaluation of the effect of a child's burn injury on parents should take into context the preexisting health of the parent. Socioeconomic factors associated with increased risk of burns may also be associated with adverse health outcomes. PMID- 26361328 TI - Pubertal BPA exposure changes central ERalpha levels in female mice. AB - Despite many studies on the effects of perinatal Bisphenol A (BPA) exposure on the brain, its effects on brain estrogen receptor (ERalpha) expression during puberty remain unclear. Here, mice were injected subcutaneously with BPA (50MUg/kg), estradiol (10MUg 17beta-E2/kg) or oil (0.05ml sesame oil) daily during puberty (postnatal days 23-30). Immunohistochemistry was used to examine changes in ERalpha immunoreactive neurons in different brain regions. Compared to control animals, pubertal exposure to BPA significantly increased ERalpha immunoreactive neurons in the bed nucleus of the stria terminalis (BST), arcuate hypothalamic nucleus (Arc), ventromedial hypothalamic nucleus (VMH) and medial amygdaloid nucleus (MeA) in females. E2 exposure during puberty also increased ERalpha immunoreactive neurons in the lateral septum (LS) of females. No effect was detected in males. These results indicate that the effects of estrogenic chemicals on ERalpha immunoreactive neurons are sex-dependent. PMID- 26361327 TI - Long-Term Skeletal Muscle Mitochondrial Dysfunction is Associated with Hypermetabolism in Severely Burned Children. AB - The long-term impact of burn trauma on skeletal muscle bioenergetics remains unknown. Here, the authors determined respiratory capacity and function of skeletal muscle mitochondria in healthy individuals and in burn victims for up to 2 years postinjury. Biopsies were collected from the m. vastus lateralis of 16 healthy men (26 +/- 4 years) and 69 children (8 +/- 5 years) with burns encompassing >=30% of their total BSA. Seventy-nine biopsies were collected from cohorts of burn victims at 2 weeks (n = 18), 6 months (n = 18), 12 months (n = 25), and 24 months (n = 18) postburn. Hypermetabolism was determined by the difference in predicted and measured metabolic rate. Mitochondrial respiration was determined in saponin-permeabilized myofiber bundles. Outcomes were modeled by analysis of variance, with differences in groups assessed by Tukey-adjusted contrasts. Burn patients were hypermetabolic for up to 2 years postinjury. Coupled mitochondrial respiration was lower at 2 weeks (17 [8] pmol/sec/mg; P < .001), 6 months (41 [30] pmol/sec/mg; P = .03), and 12 months (35 [14] pmol/sec/mg; P < .001) postburn compared with healthy controls (58 [13] pmol/sec/mg). Coupled respiration was greater at 6, 12, and 24 months postburn vs 2 weeks postburn (P < .001). Mitochondrial adenosine diphosphate and oligomycin sensitivity (measures of coupling control) were lower at all time-points postburn vs control (P < .05), but greater at 6, 12, and 24 months postburn vs 2 weeks postburn (P < .05). Muscle mitochondrial respiratory capacity remains significantly lower in burn victims for 1-year postinjury. Mitochondrial coupling control is diminished for up to 2 years postinjury in burn victims, resulting in greater mitochondrial thermogenesis. These quantitative and qualitative derangements in skeletal muscle bioenergetics likely contribute to the long-term pathophysiological stress response to burn trauma. PMID- 26361329 TI - Perfusion Intensity Correlates with Expression Levels of Psoriasis-Related Genes and Proteins. AB - BACKGROUND: Previous research revealed heterogeneity in the perfusion intensity within clinically homogenous-appearing plaques, without differences in erythema. In addition, an increased perfusion was found within the perilesional skin. This raises the question whether the heterogeneity in perfusion found both inside and outside a lesion influences the expression levels of genes and proteins involved in the pathogenesis of psoriasis. OBJECTIVES: To correlate the perfusion intensity to mRNA and protein expression of genes associated with the pathogenesis of psoriasis and to visualize the dynamics of the perfusion intensity over time using laser Doppler perfusion imaging. METHODS: Fourteen patients with plaque psoriasis were included. The superficial microcirculation and clinical local scores (single usability metric, SUM, scores) were analysed in one representative lesion every 2 weeks. After 8 weeks 4 biopsies were taken, one from a highly perfused area (hotspot) and one from a low perfusion area (coldspot) of the lesional skin, one biopsy from the highly perfused perilesional skin and one from the distant uninvolved skin. RESULTS: Statistically significant differences in mRNA and protein expression, including IL-17 and TBX21/T-Bet, were found between hotspots and coldspots, and between the highly perfused perilesional and the uninvolved skin. Hotspots tend to remain on the same location during 8 weeks of follow-up. CONCLUSIONS: Within homogenous-appearing psoriatic plaques, there are remarkable differences in mRNA and protein levels, which are correlated with the perfusion intensity and can be detected by using laser Doppler perfusion imaging. In addition, differences in mRNA and protein expression between the highly perfused perilesional skin and the uninvolved skin were found, indicating that several biological changes occur well before clinical changes become manifest. PMID- 26361330 TI - Epidemic and Endemic Malaria Transmission Related to Fish Farming Ponds in the Amazon Frontier. AB - Fish farming in the Amazon has been stimulated as a solution to increase economic development. However, poorly managed fish ponds have been sometimes associated with the presence of Anopheles spp. and consequently, with malaria transmission. In this study, we analyzed the spatial and temporal dynamics of malaria in the state of Acre (and more closely within a single county) to investigate the potential links between aquaculture and malaria transmission in this region. At the state level, we classified the 22 counties into three malaria endemicity patterns, based on the correlation between notification time series. Furthermore, the study period (2003-2013) was divided into two phases (epidemic and post epidemic). Higher fish pond construction coincided both spatially and temporally with increased rate of malaria notification. Within one malaria endemic county, we investigated the relationship between the geolocation of malaria cases (2011 2012) and their distance to fish ponds. Entomological surveys carried out in these ponds provided measurements of anopheline abundance that were significantly associated with the abundance of malaria cases within 100 m of the ponds (P < 0.005; r = 0.39). These results taken together suggest that fish farming contributes to the maintenance of high transmission levels of malaria in this region. PMID- 26361331 TI - Nanoparticles Containing Curcumin Useful for Suppressing Macrophages In Vivo in Mice. AB - To explore a novel method using liposomes to suppress macrophages, we screened food constituents through cell culture assays. Curcumin was one of the strongest compounds exhibiting suppressive effects on macrophages. We subsequently tried various methods to prepare liposomal curcumin, and eventually succeeded in preparing liposomes with sufficient amounts of curcumin to suppress macrophages by incorporating a complex of curcumin and bovine serum albumin. The diameter of the resultant nanoparticles, the liposomes containing curcumin, ranged from 60 to 100 nm. Flow cytometric analyses revealed that after intraperitoneal administration of the liposomes containing curcumin into mice, these were incorporated mainly by macrophages positive for F4/80, CD36, and CD11b antigens. Peritoneal cells prepared from mice injected in vivo with the liposomes containing curcumin apparently decreased interleukin-6-producing activities. Major changes in body weight and survival rates in the mice were not observed after administrating the liposomes containing curcumin. These results indicate that the liposomes containing curcumin are safe and useful for the selective suppression of macrophages in vivo in mice. PMID- 26361333 TI - Integrated, multi-scale, spatial-temporal cell biology--A next step in the post genomic era. AB - New microscopic approaches, high-throughput imaging, and gene editing promise major new insights into cellular behaviors. When coupled with genomic and other 'omic information and "mined" for correlations and associations, a new breed of powerful and useful cellular models should emerge. These top down, coarse grained, and statistical models, in turn, can be used to form hypotheses merging with fine-grained, bottom up mechanistic studies and models that are the back bone of cell biology. The goal of the Allen Institute for Cell Science is to develop the top down approach by developing a high throughput microscopy pipeline that is integrated with modeling, using gene edited hiPS cell lines in various physiological and pathological contexts. The output of these experiments and models will be an "animated" cell, capable of integrating and analyzing image data generated from experiments and models. PMID- 26361332 TI - Simple image-based no-wash method for quantitative detection of surface expressed CFTR. AB - Cystic fibrosis (CF) is the most common lethal genetic disease among Caucasians. It is caused by mutations in the CF Transmembrane Conductance Regulator (CFTR) gene, which encodes an apical membrane anion channel that is required for regulating the volume and composition of epithelial secretions. The most common CFTR mutation, present on at least one allele in >90% of CF patients, deletes phenylalanine at position 508 (F508del), which causes the protein to misfold. Endoplasmic reticulum (ER) quality control elicits the degradation of mutant CFTR, compromising its trafficking to the epithelial cell apical membrane. The absence of functional CFTR leads to depletion of airway surface liquid, impaired clearance of mucus and bacteria from the lung, and predisposes to recurrent infections. Ultimately, respiratory failure results from inflammation and bronchiectasis. Although high throughput screening has identified small molecules that can restore the anion transport function of F508del CFTR, they correct less than 15% of WT CFTR activity, yielding insufficient clinical benefit. To date, most primary CF drug discovery assays have employed measurements of CFTR's anion transport function, a method that depends on the recruitment of a functional CFTR to the cell surface, involves multiple wash steps, and relies on a signal that saturates rapidly. Screening efforts have also included assays for detection of extracellularly HA-tagged or HRP-tagged CFTR, which require multiple washing steps. We have recently developed tools and cell lines that report the correction of mutant CFTR trafficking by currently available small molecules, and have extended this assay to the 96-well format. This new and simple no-wash assay of F508del CFTR at the cell surface may permit the discovery of more efficacious drugs, and hopefully thereby prevent the catastrophic effects of this disease. In addition, the modular design of this platform should make it useful for other diseases where loss-of-function results from folding and/or trafficking defects in membrane proteins. PMID- 26361335 TI - Sr14Sn3As12 and Eu14Sn3As12: enantiomorph-like Zintl compounds. AB - Two new chiral Zintl compounds, Sr14Sn3As12 and Eu14Sn3As12, were synthesized from tin-flux reactions, and the structures were determined by using single crystal X-ray diffraction. Both compounds crystallize in the trigonal space group R3 (No. 146, Z = 3) with the anion structures containing various units: dumbbell shaped [Sn2As6](12-) dimers, [SnAs3](7-) triangular pyramids, and isolated As(3-) anions. Very interestingly, these two compounds exhibit opposite chirality in the observed crystal structures, resembling enantiomorphs. Detailed structure analyses suggest possible steric effects among the anion clusters, and on the basis of the calculated electronic structures, substantial electron lone pairs exist on the anions of both compounds, which may provide a hint to understanding the origination of chirality in these intermetallic compounds. PMID- 26361334 TI - PU.1 Suppresses Th2 Cytokine Expression via Silencing of GATA3 Transcription in Dendritic Cells. AB - The transcription factor PU.1 is predominantly expressed in dendritic cells (DCs) and is essential for DC differentiation. Although there are several reports that PU.1 positively regulates the expression of DC-specific genes, whether PU.1 also has a suppressive effect on DCs is largely unknown. Here we demonstrate that PU.1 suppresses the expression of Th2 cytokines including IL-13 and IL-5 in bone marrow-derived DCs (BMDCs), through repression of the expression of GATA3, which is a master regulator of Th2 differentiations. When PU.1 siRNA was introduced into BMDCs, LPS-induced expression of IL-13 and IL-5 was increased along with upregulation of the constitutive expression of GATA2 and GATA3. The additional introduction of GATA3 siRNA but not of GATA2 siRNA abrogated PU.1 siRNA-mediated upregulation of IL-13 and IL-5. A chromatin immunoprecipitation assay showed that PU.1 bound to Gata3 proximal promoter region, which is more dominant than the distal promoter in driving GATA3 transcription in DCs. The degree of histone acetylation at the Gata3 promoter was decreased in PU.1 siRNA-introduced DCs, suggesting the involvement of PU.1 in chromatin modification of the Gata3 promoter. Treatment with a histone deacetylase (HDAC) inhibitor, trichostatin A, increased the degree of histone H3 acetylation at the Gata3 promoter and induced the subsequent expression of GATA3. Experiments using HDAC inhibitors and siRNAs showed that HDAC3 suppressed GATA3 expression. The recruitment of HDAC3 to the Gata3 promoter was decreased by PU.1 knockdown. LPS-induced IL-13 expression was dramatically reduced in BMDCs generated from mice lacking the conserved GATA3 response element, termed CGRE, which is an essential site for the binding of GATA3 on the Il-13 promoter. The degree of H3K4me3 at CGRE was significantly increased in PU.1 siRNA-transfected stimulated DCs. Our results indicate that PU.1 plays pivotal roles in DC development and function, serving not only as a transcriptional activator but also as a repressor. PMID- 26361336 TI - Development of an Educational Strategy and Decision Support Tool to Enhance Appropriate Use of Stress Echocardiography at a Large Academic Medical Center: A Prospective, Pre- and Postintervention Analysis. AB - BACKGROUND: Despite previous studies demonstrating suboptimal appropriate use of stress echocardiography (SE), few interventions have been demonstrated to improve its appropriate use. The aim of this study was to develop a novel mechanism to improve the appropriateness of SE by implementing a point-of-care decision support tool and ordering requisition coupled with an educational strategy. METHODS: A prospective pre- and postintervention analysis was conducted. The intervention included education and the development and implementation of novel ordering requisition coupled with a decision support tool that integrated appropriate use criteria (AUC) for SE. RESULTS: In the baseline period, 256 consecutive stress echocardiographic studies were evaluated, and 97% were classifiable by the 2011 AUC. During the intervention period, 159 studies were evaluated (98% classifiable). The intervention resulted in an increase in the appropriate proportion from 65% to 76% and a reduction in the rarely appropriate proportion from 31% to 19% (P = .017). After adjustment for physician specialty, the postintervention period had lower odds of rarely appropriate testing (0.54; 95% CI, 0.3-0.95; P = .04). Cardiology had significant lower odds of rarely appropriate testing (0.23; 95% CI, 0.11-0.50; P < .001) compared with family practice (the reference standard). Vascular surgery had the highest odds (5.76; 95% CI, 2.18-21.52; P = .002) of rarely appropriate testing. CONCLUSION: AUC have not previously been applied to SE in a single-payer, publicly funded health system. The development of an educational intervention involving a new requisition and decision support tool that integrated AUC resulted in a significantly reduced proportion of rarely appropriate SE. Cardiologists ordered the highest proportion of appropriate SE. Further study is needed to determine the generalizability of the results. PMID- 26361337 TI - Remote para-C-H Functionalization of Arenes by a D-Shaped Biphenyl Template-Based Assembly. AB - Site-selective C-H functionalization has emerged as an efficient tool in simplifying the synthesis of complex molecules. Most often, directing group (DG) assisted metallacycle formation serves as an efficient strategy to ensure promising regioselectivity. A wide variety of ortho- and meta-C-H functionalizations stand as examples in this regard. Yet despite this significant progress, DG-assisted selective para-C-H functionalization in arenes has remained unexplored, mainly because it involves the formation of a geometrically constrained metallacyclic transition state. Here we report an easily recyclable, novel Si-containing biphenyl-based template that directs efficient functionalization of the distal p-C-H bond of toluene by forming a D-shaped assembly. This DG allows the required flexibility to support the formation of an oversized pre-transition state. By overcoming electronic and steric bias, para olefination and acetoxylation were successfully performed while undermining o- and m-C-H activation. The applicability of this D-shaped biphenyl template-based strategy is demonstrated by synthesizing various complex molecules. PMID- 26361338 TI - Assessing the atrial electromechanical coupling during atrial focal tachycardia, flutter, and fibrillation using electromechanical wave imaging in humans. AB - Minimally-invasive treatments of cardiac arrhythmias such as radio-frequency ablation are gradually gaining importance in clinical practice but still lack a noninvasive imaging modality which provides insight into the source or focus of an arrhythmia. Cardiac deformations imaged at high temporal and spatial resolution can be used to elucidate the electrical activation sequence in normal and paced human subjects non-invasively and could potentially aid to better plan and monitor ablation-based arrhythmia treatments. In this study, a novel ultrasound-based method is presented that can be used to quantitatively characterize focal and reentrant arrhythmias. Spatio-temporal maps of the full view of the atrial and ventricular mechanics were obtained in a single heartbeat, revealing with otherwise unobtainable detail the electromechanical patterns of atrial flutter, fibrillation, and tachycardia in humans. During focal arrhythmias such as premature ventricular complex and focal atrial tachycardia, the previously developed electromechanical wave imaging methodology is hereby shown capable of identifying the location of the focal zone and the subsequent propagation of cardiac activation. During reentrant arrhythmias such as atrial flutter and fibrillation, Fourier analysis of the strains revealed highly correlated mechanical and electrical cycle lengths and propagation patterns. High frame rate ultrasound imaging of the heart can be used non-invasively and in real time, to characterize the lesser-known mechanical aspects of atrial and ventricular arrhythmias, also potentially assisting treatment planning for intraoperative and longitudinal monitoring of arrhythmias. PMID- 26361339 TI - Pondering the potential of quantitative analysis of video capsule endoscopy images in the management of children with celiac disease. AB - Celiac disease is common throughout the world, affecting approximately 1% of patients of all age groups. In this review, the role of video capsule endoscopy in characterizing the small intestinal lumen of pediatric patients with celiac disease is discussed in detail. Quantitative aspects of video capsule endoscopy which may be helpful in diagnosing pediatric patients are highlighted. PMID- 26361340 TI - Digital phantoms generated by spectral and spatial light modulators. AB - A hyperspectral image projector (HIP) based on liquid crystal on silicon spatial light modulators is explained and demonstrated to generate data cubes. The HIP constructed data cubes are three-dimensional images of the spatial distribution of spectrally resolved abundances of intracellular light-absorbing oxyhemoglobin molecules in single erythrocytes. Spectrally and spatially resolved image data indistinguishable from the real scene may be used as standard data cubes, so called digital phantoms, to calibrate image sensors and validate image analysis algorithms for their measurement quality, performance consistency, and interlaboratory comparisons for quantitative biomedical imaging applications. PMID- 26361341 TI - Active limited-angle tomographic phase microscope. AB - We demonstrate an active, holographic tomography system, working with limited angle of projections, realized by optical-only, diffraction-based beam steering. The system created for this purpose is a Mach-Zehnder interferometer modified to serve as a digital holographic microscope with a high numerical aperture illumination module and a spatial light modulator (SLM). Such a solution is fast and robust. Apart from providing an elegant solution to viewing angle shifting, it also adds new capabilities of the holographic microscope system. SLM, being an active optical element, allows wavefront correction in order to improve measurement accuracy. Integrated phase data captured with different illumination scenarios within a highly limited angular range are processed by a new tomographic reconstruction algorithm based on the compressed sensing technique: total variation minimization, which is applied here to reconstruct nonpiecewise constant samples. Finally, the accuracy of full measurement and the proposed processing path is tested for a calibrated three-dimensional micro-object as well as a biological object--C2C12 myoblast cell. PMID- 26361342 TI - High temperature continuous flow synthesis of CdSe/CdS/ZnS, CdS/ZnS, and CdSeS/ZnS nanocrystals. AB - Continuous flow reactors show great promise for large-scale synthesis of quantum dots. Here, we discuss results for the synthesis of multi-layered Cd-based hybrid nanocrystals - CdSe/CdS/ZnS, CdS/ZnS, and CdSeS/ZnS - in a continuous flow reactor. The simple reactor design and liquid-phase chemistry obviate the need for preheating or in-line mixing, and the chosen reactor dimensions and operating conditions allow for high flow rates (~10 mL min(-1)). Additionally, the simple reactor design is well suited for scale-up. The CdSe/CdS/ZnS particles synthesized at elevated temperatures in the reactor exhibit quantum yields of over 60% at longer wavelengths (red region). The shell growth for these particles is conducted without the need for complex dropwise addition or SILAR shell growth procedures used in batch reactors. CdS-based particles were shown to have a higher performance when using octadecene-S instead of TOP-S, which improved the quality of shell growth. In addition, stoichiometric synthesis of the alternate CdSeS/ZnS alloy particles was conducted, removing the need for a large excess of S to offset the lower S reactivity. CdSeS/ZnS alloy nanoparticles exhibit quantum yields of about 50% in the intermediate wavelength range (500-600 nm). PMID- 26361343 TI - Hydrogen sulfide modulates cadmium-induced physiological and biochemical responses to alleviate cadmium toxicity in rice. AB - We investigated the physiological and biochemical mechanisms by which H2S mitigates the cadmium stress in rice. Results revealed that cadmium exposure resulted in growth inhibition and biomass reduction, which is correlated with the increased uptake of cadmium and depletion of the photosynthetic pigments, leaf water contents, essential minerals, water-soluble proteins, and enzymatic and non enzymatic antioxidants. Excessive cadmium also potentiated its toxicity by inducing oxidative stress, as evidenced by increased levels of superoxide, hydrogen peroxide, methylglyoxal and malondialdehyde. However, elevating endogenous H2S level improved physiological and biochemical attributes, which was clearly observed in the growth and phenotypes of H2S-treated rice plants under cadmium stress. H2S reduced cadmium-induced oxidative stress, particularly by enhancing redox status and the activities of reactive oxygen species and methylglyoxal detoxifying enzymes. Notably, H2S maintained cadmium and mineral homeostases in roots and leaves of cadmium-stressed plants. By contrast, adding H2S-scavenger hypotaurine abolished the beneficial effect of H2S, further strengthening the clear role of H2S in alleviating cadmium toxicity in rice. Collectively, our findings provide an insight into H2S-induced protective mechanisms of rice exposed to cadmium stress, thus proposing H2S as a potential candidate for managing toxicity of cadmium, and perhaps other heavy metals, in rice and other crops. PMID- 26361344 TI - (1)H NMR metabolomics to study the effects of diazepam on anisatin induced convulsive seizures. AB - The anticonvulsive properties of diazepam have been extensively studied, mainly focusing on the gamma-amino butyrate (GABA) system. The aim of this investigation was to integrally analyze the metabolic events related to neuroprotection of diazepam on anisatin-induced convulsive seizures by a NMR-based metabolomic approach combined with histopathological examination and behavior examination. Multivariate analysis on metabolic profiles of the piriform cortex and cerebellum of mice revealed that diazepam could relieve mice suffering from the convulsive seizures by recovering destructed neurotransmitter and neuromodulator metabolism, ameliorating oxidative stress, alleviating the disturbance in energy, amino acid and nucleic acid metabolism in anisatin intoxicated mice. This integrated metabolomics study provided a powerful and highly effective approach to elucidate therapeutic effects and assessed the safety of diazepam. This study should be helpful for our understanding of convulsive seizures, and provide a holistic view of the treatment effects of benzodiazepine on convulsive seizures. PMID- 26361345 TI - A Comparison of Accelerometer Cut-Points among Individuals with Coronary Artery Disease. AB - BACKGROUND: Accurate assessment of physical activity among coronary artery disease patients is important for assessing adherence to interventions. The study compared moderate-to-vigorous physical intensity activity and relationships with cardiometabolic health/fitness indicators using accelerometer cut-points developed for coronary artery disease patients versus those developed in younger and middle-aged adults. METHODS: A total of 231 adults with coronary artery disease wore an Actigraph GT3X accelerometer for >=4 days (>=10 hours/day). Moderate-to-vigorous intensity physical activity between cut-points was compared using Bland-Altman analyses. Partial spearman correlations assessed relationships between moderate-to-vigorous intensity physical activity from each cut-point with markers of cardiometabolic health and fitness while controlling for age and sex. RESULTS: Average time spent in bouts of moderate-to-vigorous intensity physical activity using coronary artery disease cut-points was significantly higher than the young (mean difference: 13.0+/-12.8 minutes/day) or middle-aged (17.0+/-15.2 minutes/day) cut-points. Young and middle-aged cut-points were more strongly correlated with body mass index, waist circumference and systolic blood pressure, while coronary artery disease cut-points had stronger relationships with triglycerides, high-density and low-density lipoproteins. All were similarly correlated with measures of fitness. CONCLUSION: Researchers need to exert caution when deciding on which cut-points to apply to their population. Further work is needed to validate which cut-points provide a true reflection of moderate to-vigorous intensity physical activity and to examine relationships among patients with varying fitness. PMID- 26361346 TI - New Metacentric Populations and Phylogenetic Hypotheses Involving Whole-Arm Reciprocal Translocation in Mus musculus domesticus from Sicily, Southern Italy. AB - The house mouse Mus musculus domesticus is characterized by more than 100 metacentric populations, due to the occurrence of Robertsonian (Rb) fusions, together with the standard all-telocentric karyotype (2n = 40). We examined G banded karyotypes of 18 mice from 10 localities in Sicily and describe 3 new metacentric populations: 'Ragusa Ibla' (IRAG), 2n = 33-36, Rb(2.4), Rb(5.6), Rb(9.16), Rb(13.17); 'Piana degli Albanesi' (IPIA), 2n = 23, Rb(1.18), Rb(2.15), Rb(3.5), Rb(4.12), Rb(6.11), Rb(7.8), Rb(9.16), Rb(10.14), Rb(13.17); 'Trapani' (ITRA), 2n = 22, Rb(1.18), Rb(2.15), Rb(3.7), Rb(4.12), Rb(5.9), Rb(6.11), Rb(8.16), Rb(10.14), Rb(13.17). Three mice belonged to the previously reported 'Castelbuono' race (ICAS), 2n = 24, which is very similar to the nearby 'Palermo' (IPAL) race, 2n = 26. Three Rb fusions not yet observed in wild mouse populations were identified: Rb(3.5), Rb(3.7) and Rb(5.9). Rb fusions shared among 4 races (IPIA, IRAG, ICAS, and IPAL) allowed us to describe their potential phylogenetic relationships. We obtained 2 alternative phylogenetic trees. The differences between them are mainly due to various modes of formation of IPIA and ITRA. In the first hypothesis, the specific Rb fusions occurred independently. In the second, those of IRAG originated from those of IPIA via whole-arm reciprocal translocations. PMID- 26361347 TI - Utility and limitations of measures of health inequities: a theoretical perspective. AB - This paper examines common approaches for quantifying health inequities and assesses the extent to which they incorporate key theories necessary for explicating the definition of health inequity. The first theoretical analysis examined the distinction between inter-individual and inter-group health inequalities as measures of health inequities. The second analysis considered the notion of fairness in health inequalities from different philosophical perspectives. To understand the extent to which different measures of health inequities incorporate these theoretical explanations, four criteria were used to assess each measure: 1) Does the indicator demonstrate inter-group or inter individual health inequalities or both; 2) Does it reflect health inequalities in relation to socioeconomic position; 3) Is it sensitive to the absolute transfer of health (outcomes, services, or both) or income/wealth between groups; 4) Could it be used to capture inequalities in relation to other population groupings (other than socioeconomic status)? The measures assessed include: before and after measures within only the disadvantaged population, range, Gini coefficient, Pseudo-Gini coefficient, index of dissimilarity, concentration index, slope and relative indices of inequality, and regression techniques. None of these measures satisfied all the four criteria, except the range. Whereas each measure quantifies a different perspective in health inequities, using a measure within only the disadvantaged population does not measure health inequities in a meaningful way, even using before and after changes. For a more complete assessment of how programs affect health inequities, it may be useful to use more than one measure. PMID- 26361350 TI - Francis Cuss. PMID- 26361348 TI - Missed opportunities for institutional delivery and associated factors among urban resident pregnant women in South Tigray Zone, Ethiopia: a community-based follow-up study. AB - BACKGROUND: Every pregnant woman is considered to be at risk and some risks may not always be foreseeable or detectable. Therefore, the presence of a skilled birth attendant at every delivery is considered to be the most critical intervention in reducing maternal mortality and morbidity. In Ethiopia, the proportion of births attended by skilled personnel in urban settings can be as low as 10%. Therefore, the main purpose of this research was to identify factors affecting unplanned home delivery in urban settings, where there is relatively good access in principle to modern healthcare institutions. DESIGN: A community based follow-up study was conducted from 17 January 2014 to 30 August 2014, among second- and third-trimester pregnant women who had planned for institutional delivery in South Tigray Zone. A systematic sampling technique was used to get a total of 522 study participants. A pre-tested and structured questionnaire was used to collect relevant data. Bivariate and multivariate data analyses were performed using SPSS version 16.0. RESULTS: The study revealed that among 465 pregnant women who planned for institutional delivery, 134 (28.8%) opted out and delivered at their home (missed opportunity). Single women (AOR 2.34, 95% CI 1.17 4.68), illiterate mothers (AOR 6.14, 95% CI 2.20-17.2), absence of antenatal clinic visit for indexed pregnancy (AOR 3.11, 95% CI 1.72-5.61), absence of obstetric complications during the index pregnancy (AOR 2.96, 95% CI 1.47-5.97), poor autonomy (AOR 2.11, 95% CI 1.27-3.49), and absence of birth preparedness and complication readiness (AOR 3.83, 95% CI 2.19-6.70) were significant predictors of unplanned home delivery. CONCLUSIONS: A significant proportion of pregnant women missed the opportunity of modern delivery assistance. Educational status, antenatal care status, lack of obstetric complications, poor autonomy, and lack of birth preparedness and complication readiness were among the important predictors of unplanned home delivery. PMID- 26361349 TI - Zebrafish as tools for drug discovery. AB - The zebrafish has become a prominent vertebrate model for disease and has already contributed to several examples of successful phenotype-based drug discovery. For the zebrafish to become useful in drug development more broadly, key hurdles must be overcome, including a more comprehensive elucidation of the similarities and differences between human and zebrafish biology. Recent studies have begun to establish the capabilities and limitations of zebrafish for disease modelling, drug screening, target identification, pharmacology, and toxicology. As our understanding increases and as the technologies for manipulating zebrafish improve, it is hoped that the zebrafish will have a key role in accelerating the emergence of precision medicine. PMID- 26361351 TI - Evaluation of Commercial Diagnostic Assays for the Specific Detection of Avian Influenza A (H7N9) Virus RNA Using a Quality-Control Panel and Clinical Specimens in China. AB - A novel avian influenza A H7N9-subtype virus emerged in China in 2013 and threatened global public health. Commercial kits that specifically detect avian influenza A (H7N9) virus RNA are urgently required to prepare for the emergence and potential pandemic of this novel influenza virus. The safety and effectiveness of three commercial molecular diagnostic assays were evaluated using a quality-control panel and clinical specimens collected from over 90 patients with confirmed avian influenza A (H7N9) virus infections. The analytical performance evaluation showed that diverse influenza H7N9 viruses can be detected with high within- and between-lot reproducibility and without cross-reactivity to other influenza viruses (H1N1 pdm09, seasonal H1N1, H3N2, H5N1 and influenza B). The detection limit of all the commercial assays was 2.83 Log10 copies/MUl [0.7 Log10TCID50/mL of avian influenza A (H7N9) virus strain A/Zhejiang/DTID ZJU01/2013], which is comparable to the method recommended by the World Health Organization (WHO). In addition, using a WHO-Chinese National Influenza Center (CNIC) method as a reference for clinical evaluation, positive agreement of more than 98% was determined for all of the commercial kits, while negative agreement of more than 99% was observed. In conclusion, our findings provide comprehensive evidence for the high performance of three commercial diagnostic assays and suggest the application of these assays as rapid and effective diagnostic tools for avian influenza A (H7N9) virus in the routine clinical practice of medical laboratories. PMID- 26361353 TI - Delays in Admittance-Controlled Haptic Devices Make Simulated Masses Feel Heavier. AB - In an admittance-controlled haptic device, input forces are used to calculate the movement of the device. Although developers try to minimize delays, there will always be delays between the applied force and the corresponding movement in such systems, which might affect what the user of the device perceives. In this experiment we tested whether these delays in a haptic human-robot interaction influence the perception of mass. In the experiment an admittance-controlled manipulator was used to simulate various masses. In a staircase design subjects had to decide which of two virtual masses was heavier after gently pushing them leftward with the right hand in mid-air (no friction, no gravity). The manipulator responded as quickly as possible or with an additional delay (25 or 50 ms) to the forces exerted by the subject on the handle of the haptic device. The perceived mass was ~10% larger for a delay of 25 ms and ~20% larger for a delay of 50 ms. Based on these results, we estimated that the delays that are present in nowadays admittance-controlled haptic devices (up to 20ms) will give an increase in perceived mass which is smaller than the Weber fraction for mass (~10% for inertial mass). Additional analyses showed that the subjects' decision on mass when the perceptual differences were small did not correlate with intuitive variables such as force, velocity or a combination of these, nor with any other measured variable, suggesting that subjects did not have a consistent strategy during guessing or used other sources of information, for example the efference copy of their pushes. PMID- 26361352 TI - Functional Role of the Disulfide Isomerase ERp57 in Axonal Regeneration. AB - ERp57 (also known as grp58 and PDIA3) is a protein disulfide isomerase that catalyzes disulfide bonds formation of glycoproteins as part of the calnexin and calreticulin cycle. ERp57 is markedly upregulated in most common neurodegenerative diseases downstream of the endoplasmic reticulum (ER) stress response. Despite accumulating correlative evidence supporting a neuroprotective role of ERp57, the contribution of this foldase to the physiology of the nervous system remains unknown. Here we developed a transgenic mouse model that overexpresses ERp57 in the nervous system under the control of the prion promoter. We analyzed the susceptibility of ERp57 transgenic mice to undergo neurodegeneration. Unexpectedly, ERp57 overexpression did not affect dopaminergic neuron loss and striatal denervation after injection of a Parkinson's disease inducing neurotoxin. In sharp contrast, ERp57 transgenic animals presented enhanced locomotor recovery after mechanical injury to the sciatic nerve. These protective effects were associated with enhanced myelin removal, macrophage infiltration and axonal regeneration. Our results suggest that ERp57 specifically contributes to peripheral nerve regeneration, whereas its activity is dispensable for the survival of a specific neuronal population of the central nervous system. These results demonstrate for the first time a functional role of a component of the ER proteostasis network in peripheral nerve regeneration. PMID- 26361354 TI - Deciphering Seed Sequence Based Off-Target Effects in a Large-Scale RNAi Reporter Screen for E-Cadherin Expression. AB - Functional RNAi based screening is affected by large numbers of false positive and negative hits due to prevalent sequence based off-target effects. We performed a druggable genome targeting siRNA screen intended to identify novel regulators of E-cadherin (CDH1) expression, a known key player in epithelial mesenchymal transition (EMT). Analysis of primary screening results indicated a large number of false-positive hits. To address these crucial difficulties we developed an analysis method, SENSORS, which, similar to published methods, is a seed enrichment strategy for analyzing siRNA off-targets in RNAi screens. Using our approach, we were able to demonstrate that accounting for seed based off target effects stratifies primary screening results and enables the discovery of additional screening hits. While traditional hit detection methods are prone to false positive results which are undetected, we were able to identify false positive hits robustly. Transcription factor MYBL1 was identified as a putative novel target required for CDH1 expression and verified experimentally. No siRNA pool targeting MYBL1 was present in the used siRNA library. Instead, MYBL1 was identified as a putative CDH1 regulating target solely based on the SENSORS off target score, i.e. as a gene that is a cause for off-target effects down regulating E-cadherin expression. PMID- 26361356 TI - Energetic derivatives of 5-(5-amino-2H-1,2,3-triazol-4-yl)-1H-tetrazole. AB - This study presents the preparation of the novel nitrogen-rich compound 5-(5 amino-2H-1,2,3-triazol-4-yl)-1H-tetrazole (5) from commercially available chemicals in a five step synthesis. The more energetic derivatives with azido (6) and nitro (7) groups, as well as a diazene bridge (8) were also successfully prepared. The energetic compounds were comprehensively characterized by various means, including vibrational (IR, Raman) and multinuclear ((1)H, (13)C, (14)N, (15)N) NMR spectroscopy, mass spectrometry and differential thermal analysis. The sensitivities towards important outer stimuli (impact, friction, electrostatic discharge) were determined according to BAM standards. The enthalpies of formation were calculated on the CBS-4M level of theory, revealing highly endothermic values, and were utilized to calculate the detonation parameters using EPXLO5 (6.02). PMID- 26361355 TI - High Throughput Sequencing Identifies MicroRNAs Mediating alpha-Synuclein Toxicity by Targeting Neuroactive-Ligand Receptor Interaction Pathway in Early Stage of Drosophila Parkinson's Disease Model. AB - Parkinson's disease (PD) is a prevalent neurodegenerative disorder with pathological features including death of dopaminergic neurons in the substantia nigra and intraneuronal accumulations of Lewy bodies. As the main component of Lewy bodies, alpha-synuclein is implicated in PD pathogenesis by aggregation into insoluble filaments. However, the detailed mechanisms underlying alpha-synuclein induced neurotoxicity in PD are still elusive. MicroRNAs are ~20nt small RNA molecules that fine-tune gene expression at posttranscriptional level. A plethora of miRNAs have been found to be dysregulated in the brain and blood cells of PD patients. Nevertheless, the detailed mechanisms and their in vivo functions in PD still need further investigation. By using Drosophila PD model expressing alpha synuclein A30P, we examined brain miRNA expression with high-throughput small RNA sequencing technology. We found that five miRNAs (dme-miR-133-3p, dme-miR-137-3p, dme-miR-13b-3p, dme-miR-932-5p, dme-miR-1008-5p) were upregulated in PD flies. Among them, miR-13b, miR-133, miR-137 are brain enriched and highly conserved from Drosophila to humans. KEGG pathway analysis using DIANA miR-Path demonstrated that neuroactive-ligand receptor interaction pathway was most likely affected by these miRNAs. Interestingly, miR-137 was predicted to regulate most of the identified targets in this pathway, including dopamine receptor (DopR, D2R), gamma-aminobutyric acid (GABA) receptor (GABA-B-R1, GABA-B-R3) and N-methyl D-aspartate (NMDA) receptor (Nmdar2). The validation experiments showed that the expression of miR-137 and its targets was negatively correlated in PD flies. Further experiments using luciferase reporter assay confirmed that miR-137 could act on specific sites in 3' UTR region of D2R, Nmdar2 and GABA-B-R3, which downregulated significantly in PD flies. Collectively, our findings indicate that alpha-synuclein could induce the dysregulation of miRNAs, which target neuroactive ligand-receptor interaction pathway in vivo. We believe it will help us further understand the contribution of miRNAs to alpha-synuclein neurotoxicity and provide new insights into the pathogenesis driving PD. PMID- 26361357 TI - Copper levels and changes in pH induce oxidative stress in the tissue of curimbata (Prochilodus lineatus). AB - We analyzed the effect of exposure to 25% 96 h-LC50 of copper at low (24.5 MUg L( 1) Cu, pH 4.5), neutral (7.25 MUg L(-1) Cu, pH 7.0) and high pH (4.0 MUg L(-1) Cu, pH 8.0) at 20 degrees C on antioxidant defenses and oxidative stress in the liver, gills and white muscle of the fish Prochilodus lineatus. Water at pH 4.5 and 8.0 affected the enzymatic and non-enzymatic antioxidant systems of the liver and gills, but not of the white muscles of P. lineatus, when compared to water at pH 7.0. After Cu exposure, SOD (superoxide dismutase), GPx (glutathione peroxidase), GR (glutathione reductase) and GST (glutathione S-transferase) activities increased and CAT (catalase) activity decreased in the liver at water at pH 4.5 and 8.0. Meanwhile, the activities of SOD, CAT, GPx, GR and GST increased in the gills at these pHs. SOD and CAT activities increased in the white muscle after Cu exposure at pH 8.0 and GPx, GR and GST activities decreased after Cu exposure at pH 4.5 and 8.0. LPO levels decreased in the liver and gills of fish that were exposed to water at pH 4.5 and 8.0 and, after Cu exposure, the LPO level increased in the liver, gills and white muscle of fish that were exposed to water at pH 4.5 and 8.0, when compared to the control group at pH 7.0. The metallothionein (MT) concentration increased in the liver of fish in water at pH 4.5 and 8.0 and the gill of fish in water at pH 8.0. After Cu exposure, MT in the liver and gills was significantly elevated in fish exposed to water at pH 4.5 and 8.0, but remained at levels similar to the control group in the white muscle. These results indicate a differing sensitivity of fish organs and tissues to essential metals, such as copper, and that toxicity may be relevant at environmental concentrations. These results indicate that the effect of Cu on the response of antioxidant defense systems is determined by water pH. PMID- 26361358 TI - Costs of gestational diabetes. PMID- 26361359 TI - Education and Imaging. Gastroenterology: Rare cause of upper gastrointestinal bleeding. PMID- 26361360 TI - Education and Imaging. Gastroenterology: Acute left-sided appendicitis with intestinal malrotation. PMID- 26361361 TI - Education and Imaging. Gastroenterology: Pneumomediastinum and pneumoperitoneum after peroral endoscopic myotomy: Complications or normal post-operative changes? PMID- 26361362 TI - Education and Imaging. Hepatobiliary and Pancreatic: Intrathoracic gallbladder herniation after radiofrequency ablation of hepatocellular carcinoma. PMID- 26361363 TI - Education and Imaging. Hepatobiliary and Pancreatic: Gas-forming liver abscess caused by Salmonella after transcatheter arterial chemoembolization for hepatocellular carcinoma. PMID- 26361364 TI - Loss of Biventricular Pacing During Exercise: What is the Mechanism? PMID- 26361365 TI - Development of standard definitions for surveillance of complications related to blood donation. AB - Standard definitions of donor reactions allow each blood establishment to monitor donor adverse events and compare with other organizations to develop best practices. The ISBT Haemovigilance Working Party leads a multi-organizational effort to update the 2008 ISBT standard for surveillance of complications related to blood donation. Revised definitions have been developed and endorsed by the ISBT, AABB, International Haemovigilance Network (IHN) and other international organizations. PMID- 26361366 TI - Comparison of Single Port Access Versus Multiple Port Access Systems in Elective Laparoscopy: 98 Dogs (2005-2014). AB - OBJECTIVE: To report and compare the duration of surgery, the frequency of complications, and the frequency of open conversion for elective surgeries performed with 2 laparoscopic techniques: a single incision port access system (SPAS) and a multiple port access system (MPAS) using a Veress needle. STUDY DESIGN: Retrospective case series. ANIMALS: Ninety-eight consecutive, client owned dogs. METHODS: Medical records of dogs undergoing an elective laparoscopic procedure were reviewed. Dogs were classified as SPAS or MPAS according to the initial surgical approach. Duration of surgery, intraoperative complications, reason for open conversion, and postoperative complications were recorded and compared. RESULTS: The duration of surgery for SPAS gastropexy (P = .0039), ovariectomy (P = .0052), and gastropexy/ovariectomy combined (P = .0002) were significantly reduced compared to corresponding MPAS procedures. Nine splenic punctures occurred during MPAS. The frequency of intraoperative complications was significantly less for SPAS (0/44) than MPAS (12/54, P = .004). Elective conversion was performed because of gastric malpositioning in 1 dog and emergent conversion was required because of bleeding from the ovarian pedicle in 2 dogs (0/44 SPAS, 3/54 MPAS, P = .250). There were 14/76 dogs with followup to suture removal with postoperative complications, all incisional (7/31 SPAS, 7/45 MPAS, P = 1.0). CONCLUSION: The use of SPAS for laparoscopy reduced surgical time and intraoperative complications in elective procedures. PMID- 26361367 TI - Evaluation of polymyxin susceptibility profile among KPC-producing Klebsiella pneumoniae using Etest and MicroScan WalkAway automated system. AB - Determination of polymyxin susceptibility profile is important to monitor resistance rates and for implementing control measures for polymyxin-resistant carbapenem-resistant Enterobacteriaceae. Some laboratorial methods have been used to determine the polymyxin susceptibility profile. However, the performance of MicroScan WalkAway has been poorly reported for KPC-producing Klebsiella pneumoniae, so far. To evaluate two different methods, Etest and the MicroScan automated system, in determining minimal inhibitory concentration (MIC) of polymyxin among KPC-producing K. pneumoniae isolated from patients in two care units (ICUs) of a tertiary hospital in Porto Alegre, Southern Brazil. A total of 101 KPC-Kb isolates were obtained from rectal swabs and clinical specimens (urine, blood, and endotracheal aspirate). Colistin and polymyxin B MICs were determined using MicroScan WalkAway automated system and Etest, respectively. Discrepant results were resolved by broth microdilution (BMD). MicroScan showed 88.1% of sensitivity for predicting polymyxin B resistance in KPC-producing K. pneumoniae compared to the results obtained by Etest. All discrepant results were tested by BMD and these were concordant with results obtained by Etest. The MicroScan automated system does not seem to be very efficient for the screening of polymyxin-resistant isolates once an inappropriate sensitivity is achieved. The results presented here show the need for confirmation of the susceptibility profile by use of a dilution method (Etest or BMD). PMID- 26361368 TI - Age Differences in Decoding Pain from the Facial Expression of Healthy Individuals and Patients with Dementia. AB - OBJECTIVE: Patients with dementia, whose ability to provide self-report of pain is often impaired, are in crucial need of observers who can detect the patients' pain-indicative behaviors appropriately, to initiate treatment. The facial display of pain promises to be especially informative for that purpose. The age of the observer has been shown to have a critical influence on observational emotion recognition (with age-related decrements in facial emotion recognition) but has not yet been studied as such for pain recognition. METHODS: For that purpose, 24 young (mean age: 24 years) and 22 older (mean age: 70 years) observers watched 120 video clips, showing facial expressions of young and old individuals with and without dementia during slight and moderate noxious stimulation. After each clip, observers were asked to rate how much pain the observed individual might have experienced. RESULTS: Young observers were superior in grading different levels of pain in the observed individuals; furthermore, their ratings corresponded better with the self-ratings of the observed individuals. However, the performance of the older observers was still sufficient as regards the differentiation of different pain levels and prediction of self-report in others. CONCLUSIONS: Age does not only lead to a decline in recognition of facial expressions of emotions but age also affects the quality of observational pain recognition in others. However, given that older observers' performance was only slightly reduced, clearly suggests that older caregivers are surely not at risk of becoming visual agnostic for the pain in others. PMID- 26361369 TI - Impaired Innate COPD Alveolar Macrophage Responses and Toll-Like Receptor-9 Polymorphisms. AB - BACKGROUND: Dysfunctional innate responses of alveolar macrophages to nontypeable Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae contribute to morbidity in chronic obstructive pulmonary disease (COPD). Our earlier studies discovered impaired COPD alveolar macrophage responses to Toll like receptor (TLR) ligands of nontypeable H. influenzae and provide rationale for further evaluation of TLR signaling. While the role of TLR single nucleotide polymorphisms is increasingly recognized in inflammatory diseases, TLR single nucleotide polymorphisms in COPD have only recently been explored. We hypothesized that specific TLR polymorphisms are associated with dysfunctional innate immune COPD alveolar macrophage responses and investigated polymorphisms of TLR2(Arg753Gln), TLR4(Thr399Ile; Asp299Gly), and TLR9(T1486C; T1237C). METHODS: DNA was purified from cells of 1) healthy nonsmokers (n = 20); 2) COPD ex-smokers (n = 83); 3) COPD active smokers (n = 93). DNA amplifications (polymerase chain reaction) were performed for each SNP. Alveolar macrophages from each group were incubated with nontypeable H. influenzae, M. catarrhalis and S. pneumoniae. Cytokine induction of macrophage supernatants was measured and the association with TLR single nucleotide polymorphism expression was determined. RESULTS: No significant inter-group differences in frequency of any TLR SNP existed. However both TLR9 single nucleotide polymorphisms were expressed in high frequency. Among COPD ex-smokers, diminished IL-8 responsiveness to nontypeable H. influenzae, M. catarrhalis and S. pneumoniae was strongly associated with carriage of TLR9(T1237C) (p = 0.02; p = 0.008; p = 0.02), but not TLR9(T1486C). Carriage of TLR9(T1237C), but not TLR9(T1486C), correlated with diminished FEV1%predicted (p = 0.037). CONCLUSION: Our results demonstrate a notable association of TLR9(T1237C) expression with dysfunctional innate alveolar macrophage responses to respiratory pathogens and with severity of COPD. PMID- 26361370 TI - Assessing HLA Antibody Strength: Have We Thought About Everything? PMID- 26361371 TI - The role of magnetic resonance imaging-T2* in the evaluation of iron overload early in hereditary hemochromatosis. A cross-sectional study with 159 patients. PMID- 26361373 TI - Erratum. AB - Monteiro-Soares M, Martins-Mendes D, Vaz-Carneiro A, Sampaio S, Dinis-Ribeiro M. Classification systems for lower extremity amputation prediction in subjects with active diabetic foot ulcer: a systematic review and meta-analysis. Diabetes Metab Res Rev 2014; 30(7): 610-622. The authors wish to bring to the readers' attention the following errors in the aforementioned paper. In Table 1, in the IDSA-IWGDF classification system validation by Lavery et al. [21], the minor LEA prevalence should be 12.6% and major 8%, instead of 48.1 and 29.6%, respectively. In the discussion section, the authors report that 'Lower extremity amputation prevalence ranged from 6.4% to 77.7%'; this sentence should, instead, read 'Lower extremity amputation prevalence ranged from 6.4% to 42.8%'. Finally, the values stated in the following sentence, 'In addition, a great variation in major LEA also occurred, with reported values ranging from 0% to 29.6%', should instead be '0% to 25%'. We apologize for this error and any confusion it may have caused. PMID- 26361372 TI - Aggregatibacter actinomycetemcomitans leukotoxin induces cytosol acidification in LFA-1 expressing immune cells. AB - Studies have suggested that Aggregatibacter actinomycetemcomitans leukotoxin (LtxA) kills human lymphocyte function-associated antigen 1 (LFA-1; CD11a/CD18) bearing immune cells through a lysosomal-mediated mechanism. Lysosomes are membrane-bound cellular organelles that contain an array of acid hydrolases that are capable of breaking down biomolecules. The lysosomal membrane bilayer confines the pH-sensitive enzymes within an optimal acidic (pH 4.8) environment thereby protecting the slightly basic cytosol (pH 6.8-7.5). In the current study, we have probed the effect of LtxA-induced cytolysis on lysosomal integrity in two different K562 erythroleukemia cell lines. K562-puro/LFA-1 cells were stably transfected with CD11a and CD18 cDNA to express LFA-1 on the cell surface while K562-puro, which does not express LFA-1, served as a control. Following treatment with 100 ng ml(-1) LtxA cells were analyzed by live cell imaging in conjunction with time-lapse confocal microscopy and by flow cytometry. Using a pH-sensitive indicator (pHrodo((r))) we demonstrated that the toxin causes a decrease in the intracellular pH in K562-puro/LFA-1 cells that is noticeable within the first 15 min of treatment. This process correlated with the disappearance of lysosomes in the cytosol as determined by both acridine orange and LysoTracker((r)) Red DND-99 staining. These changes were not observed in K562-puro cells or when heat inactivated toxin was added to K562-puro/LFA-1. Our results suggest that LtxA induces lysosomal damage, cytosol acidification, which is followed by cell death in K562-puro/LFA-1 cells. PMID- 26361374 TI - Natural killer cell phenotype modulation and natural killer/T-cell interplay in nucleos(t)ide analogue-treated hepatitis e antigen-negative patients with chronic hepatitis B. AB - Natural killer (NK) and hepatitis B virus (HBV)-specific T cells are functionally impaired in chronic hepatitis B (CHB). Understanding to what extent nucleos(t)ide analogue (NUC) therapy can improve T- and NK-cell responses is important in the perspective of immunomonitoring strategies for a safe and earlier NUC withdrawal and of novel combination therapies based on modulation of antiviral immunity. To gain further insights into T/NK-cell interplay, we studied NK-cell phenotype and function in hepatitis B e antigen-negative chronic HBV patients either untreated (25) or NUC treated (36 hepatitis B surface antigen [HBsAg](+) and 10 HBsAg( )/hepatitis B surface antibody [anti-HBs](+)). Interferon-gamma, interleukin-2, and tumor necrosis factor alpha (TNF-alpha) production by HBV-specific T cells was also analyzed in NUC-treated patients. NK cells from chronic naive patients showed an "inflammatory" phenotype defined by increased expression of TNF-related apoptosis-inducing ligand (TRAIL), CD38, and Ki67 that significantly declined upon viremia suppression and alanine aminotransferase normalization induced by NUC therapy. Reversion to a quiescent NK-cell phenotype was associated with restoration of the HBV-specific T-cell function. T- and NK-cell responses showed an inverse correlation, with an opposite behavior in individual NUC-treated patients. NK-cell depletion as well as TRAIL and NKG2D pathway blockade induced a significant improvement of the HBV-specific T-cell function. CONCLUSIONS: NK cells can express regulatory activity on T cells in NUC-treated patients with prevalent inhibition of CD4 T cells, likely needed to limit persistent T-cell activation. NK-cell phenotype is modulated by NUC therapy and its reversion to quiescence mirrors efficient HBV-specific T-cell responses. Thus, changes of NK cell phenotype may predict acquisition of antiviral control before anti-HBs seroconversion and represent the groundwork for future studies aimed at assessing whether NK phenotyping can be translated into the clinical practice to guide NUC suspension. PMID- 26361375 TI - Long-term outcome of primary congenital glaucoma in South Korea. PMID- 26361376 TI - Arrestin-Bound Rhodopsin: A Molecular Structure and its Impact on the Development of Biased GPCR Ligands. PMID- 26361377 TI - The Electronic Structure of Some Cyanohydrins-A Spectroscopically Under Investigated Family of Compounds. AB - Cyanohydrins are usually formed by addition of hydrogen cyanide to aldehydes or ketones while the elimination of HCN from cyanohydrins is easily observed upon heating. The low thermal stability of these highly boiling compounds leads to difficult studies in the gas phase where partial or complete decomposition is usually observed. Consequently, the reported physicochemical properties of such compounds in the gas phase are still scarce. Keeping with this, four simple cyanohydrins, the glycolonitrile and methyl, vinyl and ethynyl derivatives, have been selected. These are possible candidates for the Interstellar Medium, where the corresponding aldehydes and HCN have been detected, and could have played an important role in prebiotic chemistry, as already proposed for some of them. Three well-suited spectroscopic techniques, namely, UV photoelectron, infrared, and Raman spectroscopies, in tandem with quantum calculations, have been chosen for the structure analysis. Photoelectron spectroscopy, successfully performed with gaseous compounds, provides the first comparative study on cyanohydrins in the gas phase. PMID- 26361378 TI - Mesoporous Silica Nanoparticles Decorated with Carbosilane Dendrons as New Non viral Oligonucleotide Delivery Carriers. AB - A novel nanosystem based on mesoporous silica nanoparticles covered with carbosilane dendrons grafted on the external surface of the nanoparticles is reported. This system is able to transport single-stranded oligonucleotide into cells, avoiding an electrostatic repulsion between the cell membrane and the negatively charged nucleic acids thanks to the cationic charge provided by the dendron coating under physiological conditions. Moreover, the presence of the highly ordered pore network inside the silica matrix would make possible to allocate other therapeutic agents within the mesopores with the aim of achieving a double delivery. First, carbosilane dendrons of second and third generation possessing ammonium or tertiary amine groups as peripheral functional groups were prepared. Hence, different strategies were tested in order to obtain their suitable grafting on the outer surface of the nanoparticles. As nucleic acid model, a single-stranded DNA oligonucleotide tagged with a fluorescent Cy3 moiety was used to evaluate the DNA adsorption capacity. The hybrid material functionalised with the third generation of a neutral dendron showed excellent DNA binding properties. Finally, the cytotoxicity as well as the capability to deliver DNA into cells, was tested in vitro by using a human osteoblast-like cell line, achieving good levels of internalisation of the vector DNA/carbosilane dendron-functionalised material without affecting the cellular viability. PMID- 26361379 TI - Evaluation of a Gadolinium-Based Nanoparticle (AGuIX) for Contrast-Enhanced MRI of the Liver in a Rat Model of Hepatic Colorectal Cancer Metastases at 9.4 Tesla. AB - PURPOSE: The aim of this study was to compare a Gd-based nanoparticle (AGuIX) with a standard extracellular Gd-based contrast agent (Gd-DOTA) for MRI at 9.4 T in rats with hepatic colorectal cancer metastases. MATERIALS AND METHODS: 12 rats with hepatic metastases were subjected to MRI using a 9.4 T animal scanner. T1w self-gated FLASH sequences (TR/TE = 45/2.5 ms, alpha = 45 degrees , TA = 1: 23 min, FOV = 5.12 * 5.12 cm(2), matrix = 256 * 256) were acquired before and at 10 time points after contrast injection. Each animal received 0.1 mmol/kg BW Gd-DOTA i.v. 2 days later AGuIX was applied at 0.01 mmol/kg BW (representing equal Gd doses). The SNR of normal liver (SNRliver), hyper- and hypoenhancing parts of tumors (SNRtumor, hyperenh/SNRtumor, hypoenhanc), erector spinae muscle (SNRmuscle), CNR and lesion enhancement (LE) were calculated based on ROI measurements. RESULTS: Mean SNRliver (Gd-DOTA: 14.6 +/- 0.7; AGuIX: 28.2+/- 2.6, p < 0.001), SNRtumor, hyperenhanc (Gd-DOTA: 18.6 +/- 1.2; AGuIX: 29.6 +/- 2.8, p < 0.001), SNRtumor, hypoenhanc (Gd-DOTA: 12.0 +/- 0.7; AGuIX: 15.4 +/- 0.7, p < 0.001), SNRmuscle (Gd-DOTA: 12.3 +/- 0.3; AGuIX: 14.0 +/- 0.7, p < 0.001), mean CNR (Gd-DOTA: -2.5 +/- 0.2; AGuIX: -7.5 +/- 1.0, p < 0.001) and LE (Gd-DOTA: 3.8 +/- 0.7; AGuIX: 14.9 +/- 2.8, p = 0.001) were significantly higher using AGuIX. Regardless of the larger molecular size, AGuIX demonstrates an early peak enhancement followed by a continuous washout. CONCLUSION: AGuIX provides better enhancement at 9.4 T compared to Gd-DOTA for equal doses of applied Gd. This is based on the molecule structure and the subsequent increased interaction with protons leading to a higher relaxivity. AGuIX potentially ameliorates the conspicuity of focal liver lesions and may improve the sensitivity in diagnostic imaging of malignant hepatic tumors. KEY POINTS: AGuIX provides superior enhancement as compared to the extracellular compound Gd-DOTA at 9.4 T. AGuIX may improve the detection and diagnostic sensitivity of malignant focal liver lesions. The small size of AGuIX allows for fast renal clearance and prevents undesirable accumulation in the body. PMID- 26361380 TI - A single night of partial sleep loss impairs fasting insulin sensitivity but does not affect cephalic phase insulin release in young men. AB - The present study sought to investigate whether a single night of partial sleep deprivation (PSD) would alter fasting insulin sensitivity and cephalic phase insulin release (CPIR) in humans. A rise in circulating insulin in response to food-related sensory stimulation may prepare tissues to break down ingested glucose, e.g. by stimulating rate-limiting glycolytic enzymes. In addition, given insulin's anorexigenic properties once it reaches the brain, the CPIR may serve as an early peripheral satiety signal. Against this background, in the present study 16 men participated in two separate sessions: one night of PSD (4.25 h sleep) versus one night of full sleep (8.5 h sleep). In the morning following each sleep condition, subjects' oral cavities were rinsed with a 1-molar sucrose solution for 45 s, preceded and followed by blood sampling for repeated determination of plasma glucose and serum insulin concentrations (-3, +3, +5, +7, +10 and +20 min). Our main result was that PSD, compared with full sleep, was associated with significantly higher peripheral insulin resistance, as indicated by a higher fasting homeostasis model assessment of insulin resistance index (+16%, P = 0.025). In contrast, no CPIR was observed in any of the two sleep conditions. Our findings indicate that a single night of PSD is already sufficient to impair fasting insulin sensitivity in healthy men. In contrast, brief oral cavity rinsing with sucrose solution did not change serum insulin concentrations, suggesting that a blunted CPIR is an unlikely mechanism through which acute sleep loss causes metabolic perturbations during morning hours in humans. PMID- 26361381 TI - Inhibition of Osteoarthritis by Adipose-Derived Stromal Cells Overexpressing Fra 1 in Mice. AB - OBJECTIVE: To determine whether overexpression of the activator protein 1 (AP-1) transcription factor Fra-1 in adipose-derived stromal cells (ADSCs) is an effective treatment of collagenase-induced osteoarthritis (OA). METHODS: OA was induced by injection of collagenase into the knee joints of male C57BL/6 mice. ADSCs were isolated from the inguinal fat pads of 8-week-old wild-type or Fra-1 transgenic mice and injected into the knee joints of mice with collagenase induced OA 7 days after OA induction. Histologic analyses of cartilage destruction and chondrocyte cell death were performed. Adipogenic differentiation capacity was evaluated, gene expression was analyzed, and cytokine profiling was performed in stromal vascular fractions (SVFs) and ADSCs. RESULTS: OA-related cartilage destruction and chondrocyte cell death were significantly reduced in mouse knee joints treated with ADSCs from Fra-1-transgenic mice compared to mouse knee joints treated with ADSCs from wild-type mice. This effect did not result from the higher number of adipogenic progenitors observed in SVFs from Fra-1 transgenic compared to wild-type mouse fat pads, since injection of wild-type mouse ADSCs enriched for adipogenic progenitors did not show any additional chondroprotective effects compared to nonsorted ADSCs. However, Fra-1-transgenic mouse ADSCs showed decreased adipogenic differentiation capacity. Moreover, Fra-1 significantly inhibited proinflammatory interleukin-6 and pentraxin 3 expression, while increasing the expression of extracellular matrix proteins, such as periostin and spondin 1. These findings suggest that Fra-1 overexpression leads to an increased chondroprotective effect of ADSCs in OA. CONCLUSION: ADSCs overexpressing Fra-1 effectively protect against OA. Our data indicate that genetic modifications of ADSCs, such as Fra-1 overexpression, may improve their potential to protect articular cartilage against OA-mediated damage. PMID- 26361383 TI - Bilateral Bloody Otorrhagia After Robotic-Assisted Laparoscopic Prostatectomy. AB - Bloody otorrhagia in the perioperative period is an uncommon event. We present a case of bilateral bloody otorrhagia after uncomplicated robotic-assisted laparoscopic prostatectomy in a 66-year-old man. Anesthetic management was unremarkable. No symptoms were noted by the patient. Postoperative otolaryngology evaluation revealed bilateral ear canal hematomas with intact tympanic membranes. The patient was discharged with Ciprodex ear drops on postoperative day 1. One month otolaryngology follow-up revealed no long-term sequelae. Although the etiology is unclear, there seems to be a trend in the literature toward occurrence with laparoscopy in the Trendelenburg position. PMID- 26361382 TI - Age-dependent changes in amino acid phenotype and the role of glutamate release from hypothalamic proopiomelanocortin neurons. AB - Hypothalamic proopiomelanocortin (POMC) neurons are important regulators of energy balance. Recent studies indicate that in addition to their peptides, POMC neurons can release either the amino acid (AA) transmitter gamma-aminobutyric acid (GABA) or glutamate. A small subset of POMC neurons appears to have a dual AA phenotype based on coexpression of mRNA for the vesicular glutamate transporter (vGlut2) and the GABA synthetic enzyme Gad67. To determine whether the colocalization of GABAergic and glutamatergic markers may be indicative of a switch in AA transmitter phenotype, fluorescent in situ hybridization was used to detect vGlut2 and Gad mRNA in POMC neurons during early postnatal development. The percentage of POMC neurons expressing vGlut2 mRNA in POMC neurons progressively decreased from ~40% at day 1 to less than 10% by 8 weeks of age, whereas Gad67 was only expressed in ~10% of POMC neurons at day 1 and increased until ~45% of POMC neurons coexpressed Gad67 at 8 weeks of age. To determine whether the expression of vGlut2 may play a role in energy balance regulation, genetic deletion of vGlut2 in POMC neurons was accomplished using Cre-lox technology. Male, but not female, mice lacking vGlut2 in POMC neurons were unable to maintain energy balance to the same extent as control mice when fed a high-fat diet. Altogether, the results indicate that POMC neurons are largely glutamatergic early in life and that the release of glutamate from these cells is involved in sex- and diet-specific regulation of energy balance. PMID- 26361384 TI - Cerebral Arterial Gas Embolism During Upper Endoscopy. AB - Arterial gas embolism can be caused by direct entry of gas into systemic arteries or indirectly by venous-to-arterial shunting. Although arterial gas embolism is rare, most documented cases are iatrogenic, resulting from the entry of gas during procedures that involve direct vascular cannulation or intracavitary air insufflation. Of the 18 identified case reports of air embolism during endoscopy, 11 cases describe findings of cerebral arterial gas embolism during upper endoscopy. Only 1 of these occurred during endoscopic balloon dilation of an esophageal stricture. We report a rare case of cerebral arterial gas embolism in a 64-year-old woman, which occurred during endoscopic dilation of an esophageal stricture and was subsequently treated with hyperbaric oxygen therapy. In this case report, we explore the possible etiologies, clinical workup, and therapeutic management of cerebral artery gas embolisms. Hyperbaric oxygen therapy is the treatment of choice for cerebral arterial gas embolism, with earlier treatments resulting in better outcomes. PMID- 26361385 TI - Anesthetic Challenges in an Adult with Pierre Robin Sequence, Severe Juvenile Scoliosis, and Respiratory Failure. AB - Anesthesiologists have the privilege and challenge of providing care for an extremely diverse population of patients, at times in urgent or emergent situations. We present a case of a 31-year-old woman with Pierre Robin sequence, severe juvenile scoliosis, and respiratory failure who underwent successful awake nasal fiberoptic intubation for tracheostomy at an adult tertiary care medical center. Familiarity with patient conditions infrequently encountered within our practice, as well as adherence to practice guidelines, proved essential to providing our patient with the safest care possible. PMID- 26361386 TI - Ultrasound-Guided Trigger Point Injection for Serratus Anterior Muscle Pain Syndrome: Description of Technique and Case Series. AB - Chronic chest pain is a challenge, and serratus anterior muscle pain syndrome (SAMPS) is often overlooked. We have developed an ultrasound-guided technique for infiltrating local anesthetics and steroids in patients with SAMPS. In 8 patients, the duration of chronic pain was approximately 19 months. Three months after treatment, all patients had experienced a significant reduction in pain. Infiltration for SAMPS confirms the diagnosis and provides adequate pain relief. PMID- 26361387 TI - Hypotension in the Right Lateral Position Secondary to Inferior Vena Cava Abnormality. AB - Surgical positioning is accompanied by numerous anesthetic considerations, particularly its potential effects on the cardiovascular, respiratory, and nervous systems. Clinical studies have shown that lateral positioning does not affect hemodynamics; however, with the addition of trunk flexion, there is a decrease in cardiac output, which may be secondary to caval compression. In this report, we describe a unique case of hypotension that arose in a patient positioned only in the right lateral decubitus position with flexion and that was exacerbated by an abnormally narrow inferior vena cava. PMID- 26361388 TI - Suppression of Virulence of Toxigenic Vibrio cholerae by Anethole through the Cyclic AMP (cAMP)-cAMP Receptor Protein Signaling System. AB - Use of natural compounds as antivirulence drugs could be an alternative therapeutic approach to modify the outcome of bacterial infections, particularly in view of growing resistance to available antimicrobials. Here, we show that sub bactericidal concentration of anethole, a component of sweet fennel seed, could suppress virulence potential in O1 El Tor biotype strains of toxigenic Vibrio cholerae, the causative agent of the ongoing 7th cholera pandemic. The expression of cholera toxin (CT) and toxin coregulated pilus (TCP), the major virulence factors of V. cholerae, is controlled through a regulatory cascade involving activation of ToxT with synergistic coupling interaction of ToxR/ToxS with TcpP/TcpH. We present evidence that anethole inhibits in vitro expression of CT and TCP in a toxT-dependent but toxR/toxS-independent manner and through repression of tcpP/tcpH, by using bead-ELISA, western blotting and quantitative real-time RT-PCR assays. The cyclic AMP (cAMP)-cAMP receptor protein (CRP) is a well-studied global signaling system in bacterial pathogens, and this complex is known to suppress expression of tcpP/tcpH in V. cholerae. We find that anethole influences the virulence regulatory cascade by over-expressing cyaA and crp genes. Moreover, suppression of toxigenic V. cholerae-mediated fluid accumulation in ligated ileum of rabbit by anethole demonstrates its potentiality as an antivirulence drug candidate against the diseases caused by toxigenic V. cholerae. Taken altogether, these results revealing a mechanism of virulence inhibition in V. cholerae by the natural compound anethole, may have relevance in designing antivirulence compounds, particularly against multiple antibiotic resistant bacterial pathogens. PMID- 26361389 TI - Twist1 Is a TNF-Inducible Inhibitor of Clock Mediated Activation of Period Genes. AB - BACKGROUND: Activation of the immune system affects the circadian clock. Tumor necrosis factor (TNF) and Interleukin (IL)-1beta inhibit the expression of clock genes including Period (Per) genes and the PAR-bZip clock-controlled gene D-site albumin promoter-binding protein (Dbp). These effects are due to cytokine-induced interference of E-box mediated transcription of clock genes. In the present study we have assessed the two E-box binding transcriptional regulators Twist1 and Twist2 for their role in cytokine induced inhibition of clock genes. METHODS: The expression of the clock genes Per1, Per2, Per3 and of Dbp was assessed in NIH-3T3 mouse fibroblasts and the mouse hippocampal neuronal cell line HT22. Cells were treated for 4h with TNF and IL-1beta. The functional role of Twist1 and Twist2 was assessed by siRNAs against the Twist genes and by overexpression of TWIST proteins. In luciferase (luc) assays NIH-3T3 cells were transfected with reporter gene constructs, which contain a 3xPer1 E-box or a Dbp E-box. Quantitative chromatin immunoprecipitation (ChIP) was performed using antibodies to TWIST1 and CLOCK, and the E-box consensus sequences of Dbp (CATGTG) and Per1 E-box (CACGTG). RESULTS: We report here that siRNA against Twist1 protects NIH-3T3 cells and HT22 cells from down-regulation of Period and Dbp by TNF and IL-1beta. Overexpression of Twist1, but not of Twist2, mimics the effect of the cytokines. TNF down regulates the activation of Per1-3xE-box-luc, the effect being prevented by siRNA against Twist1. Overexpression of Twist1, but not of Twist2, inhibits Per1-3xE box-luc or Dbp-E-Box-luc activity. ChIP experiments show TWIST1 induction by TNF to compete with CLOCK binding to the E-box of Period genes and Dbp. CONCLUSION: Twist1 plays a pivotal role in the TNF mediated suppression of E-box dependent transactivation of Period genes and Dbp. Thereby Twist1 may provide a link between the immune system and the circadian timing system. PMID- 26361390 TI - The Cold-Inducible RNA-Binding Protein (CIRP) Level in Peripheral Blood Predicts Sepsis Outcome. AB - OBJECTIVES: Sepsis is a lethal and complex clinical syndrome caused by infection or suspected infection. Cold-inducible RNA-binding protein (CIRP) is a widely distributed cold-shock protein that plays a proinflammatory role in sepsis and that may induce organ damage. However, clinical studies regarding the use of CIRP for the prognostic evaluation of sepsis are lacking. The purpose of this research was to investigate the prognostic significance of peripheral blood concentrations of CIRP in sepsis. Sepsis was assessed using several common measures, including the Acute Physiology and Chronic Health Evaluation II (APACHE II) score; the Sepsis-related Organ Failure Assessment (SOFA) score; the lactate, serum creatinine, and procalcitonin (PCT) levels; the white blood cell (WBC) count; and the neutrophil ratio (N%). DESIGN: Sixty-nine adult patients with sepsis were enrolled in this study. According to the mortality data from the hospital, 38 patients were survivors, and 31 were nonsurvivors. The plasma levels of the biomarkers were measured and the APACHE II and SOFA scores were calculated within 24 hours of patient enrollment into our study. The CIRP level was measured via ELISA. RESULTS: The plasma level of CIRP was significantly higher in the nonsurvivors than in the survivors (median (IQR) 4.99 (2.37-30.17) ng/mL and 1.68 (1.41-13.90) ng/mL, respectively; p = 0.013). The correlations of the CIRP level with the APACHE II score (r = 0.248, p = 0.040, n = 69), the SOFA score (r = 0.323, p = 0.007, n = 69), the serum creatinine level (r = 0.316, p = 0.008, n = 69), and the PCT level (r = 0.282, p = 0.019, n = 69) were significant. Receiver operator characteristic (ROC) curve analysis showed that the area under the ROC curve (AUC) for the CIRP level was 0.674 (p = 0.013). According to Cox proportional hazards models, the CIRP level independently predicts sepsis mortality. When the CIRP level in the peripheral blood increased by 10 ng/mL, the mortality risk increased by 1.05-fold (p = 0.012). Thus, the CIRP level reflects the degree of renal injury but does not predict the severity of sepsis or organ damage. CONCLUSION: An elevated plasma concentration of CIRP was significantly associated with poor prognosis among patients with sepsis. Therefore, CIRP is a potential predictor of sepsis prognosis. PMID- 26361391 TI - Influence of Thin Slice Reconstruction on CT Brain Perfusion Analysis. AB - OBJECTIVES: Although CT scanners generally allow dynamic acquisition of thin slices (1 mm), thick slice (>=5 mm) reconstruction is commonly used for stroke imaging to reduce data, processing time, and noise level. Thin slice CT perfusion (CTP) reconstruction may suffer less from partial volume effects, and thus yield more accurate quantitative results with increased resolution. Before thin slice protocols are to be introduced clinically, it needs to be ensured that this does not affect overall CTP constancy. We studied the influence of thin slice reconstruction on average perfusion values by comparing it with standard thick slice reconstruction. MATERIALS AND METHODS: From 50 patient studies, absolute and relative hemisphere averaged estimates of cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT), and permeability-surface area product (PS) were analyzed using 0.8, 2.4, 4.8, and 9.6 mm slice reconstructions. Specifically, the influence of Gaussian and bilateral filtering, the arterial input function (AIF), and motion correction on the perfusion values was investigated. RESULTS: Bilateral filtering gave noise levels comparable to isotropic Gaussian filtering, with less partial volume effects. Absolute CBF, CBV and PS were 22%, 14% and 46% lower with 0.8 mm than with 4.8 mm slices. If the AIF and motion correction were based on thin slices prior to reconstruction of thicker slices, these differences reduced to 3%, 4% and 3%. The effect of slice thickness on relative values was very small. CONCLUSIONS: This study shows that thin slice reconstruction for CTP with unaltered acquisition protocol gives relative perfusion values without clinically relevant bias. It does however affect absolute perfusion values, of which CBF and CBV are most sensitive. Partial volume effects in large arteries and veins lead to overestimation of these values. The effects of reconstruction slice thickness should be taken into account when absolute perfusion values are used for clinical decision making. PMID- 26361392 TI - Highly Selective Anti-Cancer Activity of Cholesterol-Interacting Agents Methyl beta-Cyclodextrin and Ostreolysin A/Pleurotolysin B Protein Complex on Urothelial Cancer Cells. AB - Cholesterol content can vary distinctly between normal and cancer cells, with elevated levels in cancer cells. Here, we investigated cholesterol sequestration with methyl-beta-cyclodextrin (MCD), and pore-formation with the ostreolysin A/pleurotolysin B (OlyA/PlyB) protein complex that binds to cholesterol/sphingomyelin-rich membrane domains. We evaluated the effects on viability of T24 invasive and RT4 noninvasive human urothelial cancer cells and normal porcine urothelial (NPU) cells. Cholesterol content strongly correlated with cancerous transformation, as highest in the T24 high-grade invasive urothelial cancer cells, and lowest in NPU cells. MCD treatment induced prominent cell death of T24 cells, whereas OlyA/PlyB treatment resulted in greatly decreased viability of the RT4 low-grade noninvasive carcinoma cells. Biochemical and transmission electron microscopy analyses revealed that MCD and OlyA/PlyB induce necrotic cell death in these cancer cells, while viability of NPU cells was not significantly affected by either treatment. We conclude that MCD is more toxic for T24 high-grade invasive urothelial cancer cells, and OlyA/PlyB for RT4 low-grade noninvasive urothelial cancer cells, and neither is toxic for NPU cells. The cholesterol and cholesterol/sphingomyelin-rich membrane domains in urothelial cancer cells thus constitute a selective therapeutic target for elimination of urothelial cancer cells. PMID- 26361394 TI - Modified Clonidine Testing for Growth Hormone Stimulation Reveals alpha2 Adrenoreceptor Sub Sensitivity in Children with Idiopathic Growth Hormone Deficiency. AB - INTRODUCTION: The association between short stature and increased risk of ischemic heart disease has been subject to studies for decades. The recent discussion of cardiovascular risk during growth hormone therapy has given new importance to this question. We have hypothesized that the autonomic system is a crucial element relating to this subject. METHODS: Heart rate variability calculated from 24-hour electrocardiogram data is providing insight into the regulatory state of the autonomous nervous system and is an approved surrogate parameter for estimating cardiovascular risk. We have calculated heart rate variability during clonidine testing for growth hormone stimulation of 56 children. As clonidine is a well-known effector of the autonomous system, stimulating vagal tone and decreasing sympathetic activity, we compared the autonomous reactions of children with constitutional growth delay (CGD), growth hormone deficiency (GHD) and former small for gestational age (SGA). RESULTS: During clonidine testing children with CGD showed the expected alpha2 adrenoreceptor mediated autonomous response of vagal stimulation for several hours. This vagal reaction was significantly reduced in the SGA group and nearly non- existent in the GHD group. DISCUSSION: Children with GHD show a reduced autonomous response to clonidine indicating alpha2-adrenoreceptor sub sensitivity. This can be found prior to the start of growth hormone treatment. Since reduction of HRV is an approved surrogate parameter, increased cardiovascular risk has to be assumed for patients with GHD. In the SGA group a similar but less severe reduction of the autonomous response to clonidine was found. These findings may enrich the interpretation of the data on growth hormone therapy, which are being collected by the SAGhE study group. PMID- 26361393 TI - The Relationship between Livestock Ownership and Child Stunting in Three Countries in Eastern Africa Using National Survey Data. AB - Livestock ownership has the potential to improve child nutrition through various mechanisms, although direct evaluations of household livestock and child stunting status are uncommon. We conducted an analysis of Demographic and Health Survey (DHS) datasets from Ethiopia (2011), Kenya (2008-2009), and Uganda (2010) among rural children under 5 years of age to compare stunting status across levels of livestock ownership. We classified livestock ownership by summing reported household numbers of goats, sheep, cattle and chickens, as well as calculating a weighted score to combine multiple species. The primary association was assessed separately by country using a log-binomial model adjusted for wealth and region, which was then stratified by child diarrheal illness, animal-source foods intake, sub-region, and wealth index. This analysis included n = 8079 children from Ethiopia, n = 3903 children from Kenya, and n = 1645 from Uganda. A ten-fold increase in household livestock ownership had significant association with lower stunting prevalence in Ethiopia (Prevalence Ratio [PR] 0.95, 95% CI 0.92-0.98) and Uganda (PR 0.87, 95% CI 0.79-0.97), but not Kenya (PR 1.01, 95% CI 0.96 1.07). The weighted livestock score was only marginally associated with stunting status. The findings varied slightly by region, but not by wealth, diarrheal disease, or animal-source food intake. This analysis suggested a slightly beneficial effect of household livestock ownership on child stunting prevalence. The small effect size observed may be related to limitations of the DHS dataset or the potentially complicated relationship between malnutrition and livestock ownership, including livestock health and productivity. PMID- 26361395 TI - Genetic Environment of Plasmid Mediated CTX-M-15 Extended Spectrum Beta Lactamases from Clinical and Food Borne Bacteria in North-Eastern India. AB - BACKGROUND: The study investigated the presence of CTX-M-15 type extended spectrum beta-lactamases (ESBL), compared their genetic arrangements and plasmid types in gram negative isolates of hospital and food origin in north-east India. From September 2013 to April 2014, a total of 252 consecutive, non-duplicate clinical isolates and 88 gram negative food isolates were selected. Phenotypic and molecular characterization of ESBL genes was performed. Presence of integrons and gene cassettes were analyzed by integrase and 59 base-element PCR respectively. The molecular environments surrounding blaCTX-M and plasmid types were investigated by PCR and PCR-based replicon typing respectively. Transformation was carried out to assess plasmid transfer. Southern blotting was conducted to localize the blaCTX-M-15 genes. DNA fingerprinting was performed by ERIC-PCR. RESULTS: Prevalence of ESBL was found to be 40.8% (103/252) in clinical and 31.8% (28/88) in food-borne isolates. Molecular characterization revealed the presence of 56.3% (58/103) and 53.5% (15/28) blaCTX-M-15 in clinical and food isolates respectively. Strains of clinical and food origin were non-clonal. Replicon typing revealed that IncI1 and IncFII plasmid were carrying blaCTX-M-15 in clinical and food isolates and were horizontally transferable. The ISEcp1 element was associated with blaCTX-M-15 in both clinical and food isolates. CONCLUSIONS: The simultaneous presence of resistance determinants in non-clonal isolates of two different groups thus suggests that the microbiota of common food products consumed may serve as a reservoir for some of the drug resistance genes prevalent in human pathogens. PMID- 26361396 TI - Cross-Bridge Group Ensembles Describing Cooperativity in Thermodynamically Consistent Way. AB - The aim of this work is to incorporate cooperativity into Huxley-type cross bridge model in thermodynamically consistent way. While the Huxley-type models assume that cross-bridges act independently from each other, we take into account that each cross-bridge is influenced by its neighbors and cooperativity is induced by tropomyosin movement. For that, we introduce ensembles of cross-bridge groups connected by elastic tropomyosin. By taking into account that the mechanical displacement of tropomyosin induces free energy change of the cross bridge group ensemble, we develop the formalism for thermodynamically consistent description of the cooperativity in muscle contraction. An example model was composed to test the approach. The model parameters were found by optimization from the linear relation between oxygen consumption and stress-strain area as well as experimentally measured stress dynamics of rat trabecula. We have found a good agreement between the optimized model solution and experimental data. Simulations also showed that it is possible to study cooperativity with the approach developed in this work. PMID- 26361397 TI - Identifying effective actions to guide volunteer-based and nationwide conservation efforts for a ground-nesting farmland bird. AB - 1. Modern farming practices threaten wildlife in different ways, and failure to identify the complexity of multiple threats acting in synergy may result in ineffective management. To protect ground-nesting birds in farmland, monitoring and mitigating impacts of mechanical harvesting is crucial. 2. Here, we use 6 years of data from a nationwide volunteer-based monitoring scheme of the Montagu's harrier, a ground-nesting raptor, in French farmlands. We assess the effectiveness of alternative nest protection measures and map their potential benefit to the species. 3. We show that unprotected nests in cultivated land are strongly negatively affected by harvesting and thus require active management. Further, we show that protection from harvesting alone (e.g. by leaving a small unharvested buffer around the nest) is impaired by post-harvest predation at nests that become highly conspicuous after harvest. Measures that simultaneously protect from harvesting and predation (by adding a fence around the nest) significantly enhance nest productivity. 4. The map of expected gain from nest protection in relation to available volunteers' workforce pinpoints large areas of high expected gain from nest protection that are not matched by equally high workforce availability. This mismatch suggests that the impact of nest protection can be further improved by increasing volunteer efforts in key areas where they are low relative to the expected gain they could have. 5.Synthesis and applications. This study shows that synergistic interplay of multiple factors (e.g. mechanical harvesting and predation) may completely undermine the success of well-intentioned conservation efforts. However, identifying areas where the greatest expected gains can be achieved relative to effort expended can minimize the risk of wasted volunteer actions. Overall, this study underscores the importance of citizen science for collecting large-scale data useful for producing science and ultimately informs large-scale evidence-based conservation actions within an adaptive management framework. PMID- 26361398 TI - Particle size distributions by transmission electron microscopy: an interlaboratory comparison case study. AB - This paper reports an interlaboratory comparison that evaluated a protocol for measuring and analysing the particle size distribution of discrete, metallic, spheroidal nanoparticles using transmission electron microscopy (TEM). The study was focused on automated image capture and automated particle analysis. NIST RM8012 gold nanoparticles (30 nm nominal diameter) were measured for area equivalent diameter distributions by eight laboratories. Statistical analysis was used to (1) assess the data quality without using size distribution reference models, (2) determine reference model parameters for different size distribution reference models and non-linear regression fitting methods and (3) assess the measurement uncertainty of a size distribution parameter by using its coefficient of variation. The interlaboratory area-equivalent diameter mean, 27.6 nm +/- 2.4 nm (computed based on a normal distribution), was quite similar to the area equivalent diameter, 27.6 nm, assigned to NIST RM8012. The lognormal reference model was the preferred choice for these particle size distributions as, for all laboratories, its parameters had lower relative standard errors (RSEs) than the other size distribution reference models tested (normal, Weibull and Rosin Rammler-Bennett). The RSEs for the fitted standard deviations were two orders of magnitude higher than those for the fitted means, suggesting that most of the parameter estimate errors were associated with estimating the breadth of the distributions. The coefficients of variation for the interlaboratory statistics also confirmed the lognormal reference model as the preferred choice. From quasi linear plots, the typical range for good fits between the model and cumulative number-based distributions was 1.9 fitted standard deviations less than the mean to 2.3 fitted standard deviations above the mean. Automated image capture, automated particle analysis and statistical evaluation of the data and fitting coefficients provide a framework for assessing nanoparticle size distributions using TEM for image acquisition. PMID- 26361399 TI - Limit of the Accuracy of Parameter Estimation for Two Molecules Moving in Close Proximity. AB - Biomolecular interactions are central to biological processes and typically take place at nanometer scale distances. They often involve molecular motion which is known to affect the accuracy of the parameter estimates. Therefore, in this paper, we consider a case of two closely spaced molecules with planar trajectory and present a general expression of the Fisher information matrix in terms of their trajectory from which the benchmark for the accuracy of the parameter estimates is obtained. Through simulations, we show its application in the case of two moving objects and another case where only one of the two objects is moving. It is shown that the deterioration of the limit of the accuracy is not only dependent on the proximity of their starting position but also on their speed and direction of movement. The effect of differing photon emission intensities on the limit of the accuracy of parameter estimation is also investigated. PMID- 26361400 TI - Toward Developing a New Occupational Exposure Metric Approach for Characterization of Diesel Aerosols. AB - The extensive use of diesel-powered equipment in mines makes the exposure to diesel aerosols a serious occupational issue. The exposure metric currently used in U.S. underground noncoal mines is based on the measurement of total carbon (TC) and elemental carbon (EC) mass concentration in the air. Recent toxicological evidence suggests that the measurement of mass concentration is not sufficient to correlate ultrafine aerosol exposure with health effects. This urges the evaluation of alternative measurements. In this study, the current exposure metric and two additional metrics, the surface area and the total number concentration, were evaluated by conducting simultaneous measurements of diesel ultrafine aerosols in a laboratory setting. The results showed that the surface area and total number concentration of the particles per unit of mass varied substantially with the engine operating condition. The specific surface area (SSA) and specific number concentration (SNC) normalized with TC varied two and five times, respectively. This implies that miners, whose exposure is measured only as TC, might be exposed to an unknown variable number concentration of diesel particles and commensurate particle surface area. Taken separately, mass, surface area, and number concentration did not completely characterize the aerosols. A comprehensive assessment of diesel aerosol exposure should include all of these elements, but the use of laboratory instruments in underground mines is generally impracticable. The article proposes a new approach to solve this problem. Using SSA and SNC calculated from field-type measurements, the evaluation of additional physical properties can be obtained by using the proposed approach. PMID- 26361401 TI - The crown jewelry of the surgeries for pancreatic cancer. PMID- 26361402 TI - Early detection of pancreatic cancer. AB - Pancreatic adenocarcinoma is a low-incident but highly mortal disease. It accounts for only 3% of estimated new cancer cases each year but is currently the fourth common cause of cancer mortality. By 2030, it is expected to be the 2(nd) leading cause of cancer death. There is a clear need to diagnose and classify pancreatic cancer at earlier stages in order to give patients the best chance at a definitive cure through surgery. Three precursor lesions that distinctly lead to pancreatic adenocarcinoma have been identified, and we have increasing understanding the non-genetic and genetic risk factors for the disease. With increased understanding about the risk factors, the familial patters, and associated accumulation of genetic mutations involved in pancreatic cancer, we know that there are mutations that occur early in the development of pancreatic cancer and that improved genetic risk-based strategies in screening for pancreatic cancer may be possible and successful at saving or prolonging lives. The remaining challenge is that current standards for diagnosing pancreatic cancer remain too invasive and too costly for widespread screening for pancreatic cancer. Furthermore, the promises of noninvasive methods of detection such as blood, saliva, and stool remain underdeveloped or lack robust testing. However, significant progress has been made, and we are drawing closer to a strategy for the screening and early detection of pancreatic cancer. PMID- 26361403 TI - Pancreatic cancer surgery: past, present, and future. AB - The history of pancreatic cancer surgery, though fraught with failure and setbacks, is punctuated by periods of incremental progress dependent upon the state of the art and the mettle of the surgeons daring enough to attempt it. Surgical anesthesia and the aseptic techniques developed during the latter half of the 19(th) century were instrumental in establishing a viable setting for pancreatic surgery to develop. Together, they allowed for bolder interventions and improved survival through the post-operative period. Surgical management began with palliative procedures to address biliary obstruction in advanced disease. By the turn of the century, surgical pioneers such as Alessandro Codivilla and Walther Kausch were demonstrating the technical feasibility of pancreatic head resections and applying principles learned from palliation to perform complicated anatomical reconstructions. Allen O. Whipple, the namesake of the pancreaticoduodenectomy (PD), was the first to take a systematic approach to refining the procedure. Perhaps his greatest contribution was sparking a renewed interest in the surgical management of periampullary cancers and engendering a community of surgeons who advanced the field through their collective efforts. Though the work of Whipple and his contemporaries legitimized PD as an accepted surgical option, it was the establishment of high-volume centers of excellence and a multidisciplinary approach in the later decades of the 20(th) century that made it a viable surgical option. Today, pancreatic surgeons are experimenting with minimally invasive surgical techniques, expanding indications for resection, and investigating new methods for screening and early detection. In the future, the effective management of pancreatic cancer will depend upon our ability to reliably detect the earliest cancers and precursor lesions to allow for truly curative resections. PMID- 26361404 TI - Advances of stereotactic body radiotherapy in pancreatic cancer. AB - Pancreatic cancer (PCA) is one of the most aggressive tumors with few effective treatment modalities. It is the 4th and 7th leading cause of cancer death in the United States and China, respectively. At the time of diagnosis, only 20% of cases present with a resectable tumor, and about 40% with a locally advanced tumor that is considered unresectable. Even resected patients still have a poor prognosis, with an incidence of local recurrence ranging from 20% to 60%. It is also reported that up to 30% of PCA patients die from locally obstructive disease with few or no distant metastases. These findings have highlighted the importance of local radiation therapy in the treatment of PCA. As the role of conventional chemoradiotherapy remains controversial, the dawn of the pancreas stereotactic body radiation therapy (SBRT) era represents a potential paradigm shift in the management of PCA. SBRT delivers a higher biological effective dose to the tumor with sharp dose escalation in a shorter treatment time course. Pancreas SBRT is a novel therapeutic option to achieve local tumor control with minimal toxicity. Herein, we review the advancement of SBRT for PCA patients with different stages of pancreatic adenocarcinoma. PMID- 26361406 TI - Laparoscopic pancreaticoduodenectomy: a descriptive and comparative review. AB - Laparoscopic pancreaticoduodenectomy (LPD) is an extremely challenging surgery. First described in 1994, it has been slow to gain in popularity. Recently, however, we have seen an increase in the number of centers performing this operation, including our own institution, as well as an increase in the quantity of published data. The purpose of this review is to describe the current status of LPD as described in the literature. We performed a literature search in the PubMed database using MeSH terms "laparoscopy" and "pancreaticoduodenectomy". We then identified articles in the English language with over 20 patients that focused on LPD only. Review articles were excluded and only one article per institution was used for descriptive analysis in order to avoid overlap. There were a total of eight articles meeting review criteria, consisting of 492 patients. On descriptive analysis we found that percent of LPD due to high-grade malignancy averaged 47% over all articles. Average operative time was 452 minutes, blood loss 369 cc's, pancreatic leak rate 15%, delayed gastric emptying 8.6%, length of hospital stay 9.4 days, and short term mortality 2.3%. Comparison studies between open pancreaticoduodenectomy (OPD) and LPD suggested decreased blood loss, longer operative time, similar post-operative complication rate, decreased pain, and shorter hospital length of stay for LPD. There was also increased number of lymph nodes harvested and similar margin free resections with LPD in the majority of studies. LPD is a safe surgery, providing many of the advantages typically associated with laparoscopic procedures. We expect this operation to continue to gain in popularity as well as be offered in increasingly more complex cases. In future studies, it will be beneficial to look further at the oncologic outcome data of LPD including survival. PMID- 26361405 TI - Surgery for oligometastasis of pancreatic cancer. AB - The incidence of pancreatic adenocarcinoma (PDAC) has steadily increased over the past several decades. The majority of PDAC patients will present with distant metastases, limiting surgical management in this population. Hepatectomy and pulmonary metastasectomy (PM) has been well established for colorectal cancer patients with isolated, resectable hepatic or pulmonary metastatic disease. Recent advancements in effective systemic therapy for PDAC have led to the selection of certain patients where metastectomy may be potentially indicated. However, the indication for resection of oligometastases in PDAC is not well defined. This review will discuss the current literature on the surgical management of metastatic disease for PDAC with a specific focus on surgical resection for isolated hepatic and pulmonary metastases. PMID- 26361408 TI - Surgical treatment of pancreatic head cancer: concept revolutions and arguments. AB - As we have a deeper and more thorough understanding of the biological behavior of pancreatic head cancer, surgical treatment concepts of this lethal disease are changing all the time. Meanwhile, numerous arguments emerge. Thus, we will probe into the focuses and arguments in the surgical treatment of pancreatic head cancer in this article, including the scope of lymphadenectomy, total mesopancreas excision (TMpE), vascular resection, minimally invasive pancreaticoduodenectomy (PD), palliative resection, surgery for recurrent disease and surgery for primary pancreatic cancer and liver metastasis. PMID- 26361407 TI - Immunotherapy for pancreatic ductal adenocarcinoma: an overview of clinical trials. AB - Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer related death and current therapeutic strategies are often unsatisfactory. Identification and development of more efficacious therapies is urgently needed. Immunotherapy offered encouraging results in preclinical models during the last decades, and several clinical trials have explored its therapeutic application in PDAC. The aim of this review is to summarize the results of clinical trials conducted to evaluate the future perspective of immunotherapy in the treatment of PDAC. PMID- 26361409 TI - Comparison of postoperative complications between internal and external pancreatic duct stenting during pancreaticoduodenectomy: a meta-analysis. AB - BACKGROUND: Two types of pancreatic duct stents are used to improve postoperative outcomes of pancreatic anastomosis. The aim of this meta-analysis was to evaluate and compare the postoperative outcomes of patients with internal or external stenting during pancreaticoduodenectomy (PD). METHODS: We searched PubMed, EMBASE, the Cochrane Library and Web of Science databases until the end of December, 2014. Studies comparing outcomes of external vs. internal stent placement in PD were eligible for inclusion. Included literature was extracted and assessed by two independent reviewers. RESULTS: Seven articles were identified for inclusion: three randomized controlled trials (RCTs) and four observational clinical studies (OCS). The meta-analyses revealed that use of external stents had advantage on reducing the incidences of pancreatic fistula (PF) in total [odds ratio (OR) =0.69; 95% confidence interval (CI), 0.48-0.99; P=0.04], PF in soft pancreas (OR =0.30; 95% CI, 0.16-0.56; P=0.0002) and delayed gastric emptying (DGE) (OR =0.58; 95% CI, 0.38-0.89; P=0.01) compared with internal stents. There were no significant differences in other postoperative outcomes between two stenting methods, including postoperative morbidity (OR =0.93; 95% CI, 0.39-2.23; P=0.88), overall mortality (OR =0.70; 95% CI, 0.22 2.25; P=0.55), and intra-abdominal collections (OR =0.67; 95% CI, 0.26-1.71; P=0.40). CONCLUSIONS: Based upon this meta-analysis, the use of external pancreatic stents might have potential benefit in reducing the incidence of PF and DGE. Due to the limited number of original studies, more RCTs are needed to further support our result and clarify the issue. PMID- 26361411 TI - On pancreatic cancer screening by magnetic resonance imaging with the recent evidence by Del Chiaro and colleagues. PMID- 26361410 TI - Impact of adjuvant treatment modalities on survival outcomes in curatively resected pancreatic and periampullary adenocarcinoma. AB - BACKGROUND: We examined the impact of adjuvant modalities on resected pancreatic and periampullary adenocarcinoma (PAC). METHODS: A total of 563 patients who were curatively resected for PAC were retrospectively analyzed between 2003 and 2013. RESULTS: Of 563 patients, 472 received adjuvant chemotherapy (CT) alone, chemoradiotherapy (CRT) alone, and chemoradiotherapy plus chemotherapy (CRT-CT) were analyzed. Of the 472 patients, 231 were given CRT-CT, 26 were given CRT, and 215 were given CT. The median recurrence-free survival (RFS) and overall survival (OS) were 12 and 19 months, respectively. When CT and CRT-CT groups were compared, there was no significant difference with respect to both RFS and OS, and also there was no difference in RFS and OS among CRT-CT, CT and CRT groups. To further investigate the impact of radiation on subgroups, patients were stratified according to lymph node status and resection margins. In node-positive patients, both RFS and OS were significantly longer in CRT-CT than CT. In contrast, there was no significant difference between groups when patients with node-negative disease or patients with or without positive surgical margins were considered. CONCLUSIONS: Addition of radiation to CT has a survival benefit in patients with node-positive disease following pancreatic resection. PMID- 26361412 TI - Chinese Anti-Cancer Association as a non-governmental organization undertakes systematic cancer prevention work in China. AB - Cancer has become the first leading cause of death in the world, particularly in low- and middle-income countries. Facing the increasing trend of cancer incidence and mortality, China issued and implemented "three-early (early prevention, early diagnosis and early treatment)" national cancer prevention plan. As the main body and dependence of social governance, non-governmental organizations (NGOs) take over the role of government in the field of cancer prevention and treatment. American Cancer Society (ACS) made a research on cancer NGOs and civil society in cancer control and found that cancer NGOs in developing countries mobilize civil society to work together and advocate governments in their countries to develop policies to address the growing cancer burden. Union for International Cancer Control (UICC), Cancer Council Australia (CCA), and Malaysian cancer NGOs are the representatives of cancer NGOs in promoting cancer control. Selecting Chinese Anti-Cancer Association (CACA) as an example in China, this article is to investigate how NGOs undertake systematic cancer prevention work in China. By conducting real case study, we found that, as a NGO, CACA plays a significant role in intensifying the leading role of government in cancer control, optimizing cancer outcomes, decreasing cancer incidence and mortality rates and improving public health. PMID- 26361413 TI - Prognostic effect analysis of molecular subtype on young breast cancer patients. AB - OBJECTIVE: To make a prognostic effect analysis of molecular subtype on young breast cancer patients. METHODS: Totally 187 cases of young breast cancer patients less than 40 years old treated in Obstetrics and Gynecology Hospital of Fudan University between June 2005 and June 2011 were included in our study. We described their clinical-pathological characteristics, disease-free survival (DFS) rate, and overall survival (OS) rate after a median follow-up period of 61 months. The factors associated with prognosis were also evaluated by univariate and multivariate analyses. RESULTS: All patients were premenopausal, with an average age of 35.36+/-3.88 years old. The mean tumor size was 2.43+/-1.53 cm. Eighty-one cases had lymph node metastasis (43.3%), 126 cases had lymphovascular invasion (67.4%), and 125 cases had histological grade III (66.8%) disease. Twenty-seven cases (14.4%) were Luminal A subtype, 99 cases (52.9%) were Luminal B subtype, 29 cases (15.5%) were human epidermal growth factor receptor 2 (HER-2) overexpression subtype, while 32 cases (17.1%) were triple negative breast cancer (TNBC) subtype according to 2013 St Gallen expert consensus. One hundred and thirty-five cases underwent mastectomy whereas 52 cases had breast-conserving surgery. One hundred and seventy-eight cases underwent adjuvant or neoadjuvant chemotherapy. Recurrence or metastasis occurred in 29 cases, 13 of which died. The 5-year DFS and OS rates were 84% and 92%. Multivariate analysis showed that nodal status (P=0.041) and molecular subtype (P=0.037) were both independent prognostic factors of DFS, while nodal status (P=0.037) and TNBC subtype (P=0.048) were both independent prognostic factors of OS. CONCLUSIONS: Molecular subtype is an independent prognostic factor of young breast cancer patients. TNBC has a high risk of relapse and death. PMID- 26361414 TI - Pediatric intestinal motility disorders. AB - Pediatric intestinal motility disorders affect many children and thus not only impose a significant impact on pediatric health care in general but also on the quality of life of the affected patient. Furthermore, some of these conditions might also have implications for adulthood. Pediatric intestinal motility disorders frequently present as chronic constipation in toddler age children. Most of these conditions are functional, meaning that constipation does not have an organic etiology, but in 5% of the cases, an underlying, clearly organic disorder can be identified. Patients with organic causes for intestinal motility disorders usually present in early infancy or even right after birth. The most striking clinical feature of children with severe intestinal motility disorders is the delayed passage of meconium in the newborn period. This sign is highly indicative of the presence of Hirschsprung disease (HD), which is the most frequent congenital disorder of intestinal motility. HD is a rare but important congenital disease and the most significant entity of pediatric intestinal motility disorders. The etiology and pathogenesis of HD have been extensively studied over the last several decades. A defect in neural crest derived cell migration has been proven as an underlying cause of HD, leading to an aganglionic distal end of the gut. Numerous basic science and clinical research related studies have been conducted to better diagnose and treat HD. Resection of the aganglionic bowel remains the gold standard for treatment of HD. Most recent studies show, at least experimentally, the possibility of a stem cell based therapy for HD. This editorial also includes rare causes of pediatric intestinal motility disorders such as hypoganglionosis, dysganglionosis, chronic intestinal pseudo-obstruction and ganglioneuromatosis in multiple endocrine metaplasia. Underlying organic pathologies are rare in pediatric intestinal motility disorders but must be recognized as early as possible. PMID- 26361415 TI - Cardiovascular involvement in inflammatory bowel disease: Dangerous liaisons. AB - Increasing evidence of a link between inflammatory bowel disease (IBD) and adverse cardiovascular events has emerged during the last decade. In 2014, an important number of meta-analyses and cohort studies clarified the subtle dangerous liaisons between gut inflammation and cardiovascular pathology. The evidence suggests that patients with IBD have a significantly increased risk of myocardial infarction, stroke, and cardiovascular mortality, especially during periods of IBD activity. Some populations (e.g., women, young patients) may have an even greater risk. Current effective treatment of IBD is aimed at disease remission and seems to reduce cardiovascular risk in these patients. A beneficial effect was demonstrated for salicylates, but not for steroids or azathioprine. tumor necrosis factor-alpha antagonists, which are highly effective in the reduction of inflammation and in the restoration of the digestive mucosa, lead to conflicting cardiovascular effects, as they seem to reduce the risk for ischemic heart disease but increase the rate of cerebrovascular events. Future supplemental treatment strategies that may reduce the atherothrombotic risk during periods of IBD activity should be explored. PMID- 26361416 TI - Value of screening endoscopy in evaluation of esophageal, gastric and colon cancers. AB - Esophageal, gastric, and colorectal cancers are deadly diseases that continue to plague our world today. The value of screening endoscopy in evaluating these types of cancers is a critical area of discussion due to a potential reduction in morbidity and mortality. This article describes how to identify a good screening test and explains what are important criteria in the field of screening endoscopy. Furthermore, the current status and progress of screening endoscopy for esophageal, gastric, and colorectal cancer will be evaluated and discussed. Mass screening programs have not been implemented for esophageal and gastric carcinomas in those with average or low risk populations. However, studies of high-risk populations have found value and a cost-benefit in conducting screening endoscopy. Colorectal cancer, on the other hand, has had mass screening programs in place for many years due to the clear evidence of improved outcomes. As the role of endoscopy as a screening tool has continued to develop, newer technology and techniques have emerged to improve its utility. Many new image enhancement techniques and computer processing programs have shown promise and may have a significant role in the future of endoscopic screening. These developments are paving the way for improving the diagnostic and therapeutic capability of endoscopy in the field of gastroenterology. PMID- 26361417 TI - Contactin 1: A potential therapeutic target and biomarker in gastric cancer. AB - Despite advances in diagnosis and treatment, gastric cancer remains one of the most common malignant tumors worldwide, and early diagnosis remains a challenge. The lack of effective methods to detect these tumors early is a major factor contributing to the high mortality in patients with gastric cancer, who are typically diagnosed at an advanced stage. Additionally, the early detection of metastases and the curative treatment of gastric cancer are difficult to achieve, and the detailed mechanisms remain to be fully elucidated. Thus, the identification of valuable predictive biomarkers and therapeutic targets to improve the prognosis of patients with gastric cancer is becoming increasingly important. Contactin 1 (CNTN1), a cell adhesion molecule, is a glycosylphosphatidylinositol-anchored neuronal membrane protein that plays an important role in cancer progression. The expression of CNTN1 is upregulated in primary lesions, and its expression level correlates with tumor metastasis in cancer patients. The current evidence reveals that the functions of CNTN1 in the development and progression of cancer likely promote the invasion and metastasis of cancer cells via the VEGFC/FLT4 axis, the RHOA-dependent pathway, the Notch signaling pathway and the epithelial-mesenchymal transition progression. Therefore, CNTN1 may be a novel biomarker and a possible therapeutic target in cancer treatment in the near future. PMID- 26361418 TI - Role of cancer-associated fibroblasts in invasion and metastasis of gastric cancer. AB - Cancer-associated fibroblasts (CAFs) are important components of various types of tumors, including gastric cancer (GC). During tumorigenesis and progression, CAFs play critical roles in tumor invasion and metastasis via a series of functions including extracellular matrix deposition, angiogenesis, metabolism reprogramming and chemoresistance. However, the mechanism of the interaction between gastric cancer cells and CAFs remains largely unknown. MicroRNAs (miRNAs) are a class of non-coding small RNA molecules, and their expression in CAFs not only regulates the expression of a number of target genes but also plays an essential role in the communication between tumor cells and CAFs. In this review, we provide an overview of recent studies on CAF miRNAs in GC and the relevant signaling pathways in gastrointestinal tumors. Focusing the attention on these signaling pathways may help us better understand their role in tumor invasion and metastasis and identify new molecular targets for therapeutic strategies. PMID- 26361419 TI - Notch1 downregulation combined with interleukin-24 inhibits invasion and migration of hepatocellular carcinoma cells. AB - AIM: To confirm the anti-invasion and anti-migration effects of down-regulation of Notch1 combined with interleukin (IL)-24 in hepatocellular carcinoma (HCC) cells. METHODS: gamma-secretase inhibitors (GSIs) were used to down-regulate Notch1. HepG2 and SMMC7721 cells were seeded in 96-well plates and treated with GSI-I or/and IL-24 for 48 h. Cell viability was measured by MTT assay. The cellular and nuclear morphology was observed under a fluorescence microscope. To further verify the apoptotic phenotype, cell cultures were also analyzed by flow cytometry with Annexin V-FITC/propidium iodide staining. The expression of Notch1, SNAIL1, SNAIL2, E-cadherin, IL-24, XIAP and VEGF was detected by Western blot. The invasion and migration capacities of HCC cells were detected by wound healing assays. Notch1 and Snail were down-regulated by RNA interference, and the target proteins were analyzed by Western blot. To investigate the mechanism of apoptosis, we analyzed HepG2 cells treated with siNotch1 or siCON plus IL-24 or not for 48 h by caspase-3/7 activity luminescent assay. RESULTS: GSI-I at a dose of 2.5 MUmol/L for 24 h caused a reduction in cell viability of about 38% in HepG2 cells. The addition of 50 ng/mL IL-24 in combination with 1 or 2.5 MUmol/L GSI-I reduced cell viability of about 30% and 15%, respectively. Treatment with IL-24 alone did not induce any cytotoxic effect. In SMMC7721 cells with the addition of IL-24 to GSI-I (2.5 MUmol/L), the reduction of cell viability was only about 25%. Following GSI-I/IL-24 combined treatment for 6 h, the apoptotic rate of HepG2 cells was 47.2%, while no significant effect was observed in cells treated with the compounds employed separately. Decreased expression of Notch1 and its associated proteins SNAIL1 and SNAIL2 was detected in HepG2 cells. Increased E-cadherin protein expression was noted in the presence of IL-24 and GSI-I. Furthermore, the increased GSI-I and IL-24 in HepG2 cell was associated with downregulation of MMP-2, XIAP and VEGF. In the absence of treatment, HepG2 cells could migrate into the scratched space in 24 h. With IL-24 or GSI-I treatment, the wound was still open after 24 h. And the distance of the wound closure strongly correlated with the concentrations of IL-24 and GSI-I. Treatment of Notch-1 silenced HepG2 cells with 50 ng/mL IL-24 alone for 48 h induced cytotoxic effects very similar to those observed in non-silenced cells treated with GSI-I/IL-24 combination. Caspase-3/7 activity was increased in the presence of siNotch1 plus IL-24 treatment. CONCLUSION: Down-regulation of Notch1 by GSI-I or siRNA combined with IL-24 can sensitize apoptosis and decrease the invasion and migration capabilities of HepG2 cells. PMID- 26361420 TI - Comparison of two types of colectomy in treating slow transit constipation with or without melanosis coli. AB - AIM: To compare the follow-up outcomes of ileosigmoidal anastomosis (ISA) and caecorectal anastomosis (CRA) in patients with slow transit constipation (STC) with or without melanosis coli (MC). METHODS: We collected the clinical data of 48 STC patients with or without MC from May 2002 to May 2007. Twenty-six patients underwent CRA (14 with MC) and 22 cases received ISA (14 with MC). A 3-year postoperative follow-up was conducted. RESULTS: CRA improved the quality of life [evaluated by the gastrointestinal quality of life index (GIQLI)] in patients without MC, but was inferior to ISA in stool frequency and Wexner and GIQLI scores for MC patients. In the CRA group, patients with MC suffered worse outcomes than those without MC. CONCLUSION: CRA is more suitable for STC patients without MC; however, for STC patients with MC, ISA is a better choice. PMID- 26361421 TI - Hepatic fat quantification magnetic resonance for monitoring treatment response in pediatric nonalcoholic steatohepatitis. AB - AIM: To evaluate the possibility of treatment effect monitoring using hepatic fat quantification magnetic resonance (MR) in pediatric nonalcoholic steatohepatitis (NASH). METHODS: We retrospectively reviewed the medical records of patients who received educational recommendations and vitamin E for NASH and underwent hepatic fat quantification MR from 2011 to 2013. Hepatic fat fraction (%) was measured using dual- and triple-echo gradient-recalled-echo sequences at 3T. The compliant and non-compliant groups were compared clinically, biochemically, and radiologically. RESULTS: Twenty seven patients (M:F = 24:3; mean age: 12 +/- 2.3 years) were included (compliant group = 22, non-compliant = 5). None of the baseline findings differed between the 2 groups, except for triglyceride level (compliant vs non-compliant, 167.7 mg/dL vs 74.2 mg/dL, P = 0.001). In the compliant group, high-density lipoprotein increased and all other parameters decreased after 1-year follow-up. However, there were various changes in the non compliant group. Dual-echo fat fraction (-19.2% vs 4.6, P < 0.001), triple-echo fat fraction (-13.4% vs 3.5, P < 0.001), alanine aminotransferase (-110.7 IU/L vs -10.6 IU/L, P = 0.047), total cholesterol (-18.1 mg/dL vs 3.8 mg/dL, P = 0.016), and triglyceride levels (-61.3 mg/dL vs 11.2 mg/dL, P = 0.013) were significantly decreased only in the compliant group. The change in body mass index and dual echo fat fraction showed a positive correlation (rho = 0.418, P = 0.030). CONCLUSION: Hepatic fat quantification MR can be a non-invasive, quantitative and useful tool for monitoring treatment effects in pediatric NASH. PMID- 26361422 TI - Annexin A10 expression in colorectal cancers with emphasis on the serrated neoplasia pathway. AB - AIM: To validate the utility of Annexin A10 as a surrogate marker of the serrated neoplasia pathway in invasive colorectal cancers (CRCs). METHODS: A total of 1133 primary CRC patients who underwent surgical resection at Seoul National University Hospital between January 2004 and December 2007 were enrolled. Expression of Annexin A10 was evaluated by immunohistochemistry using tissue microarray and paired to our findings on clinicopathologic and molecular characteristics of each individual. CpG island methylator phenotype was determined by MethyLight assay and microsatellite instability was determined by high performance liquid chromatography. KRAS and BRAF mutation status was evaluated by direct sequencing and allele-specific PCR. Univariate and stage specific survival analyses were performed to reveal the prognostic value of Annexin A10 expression. RESULTS: Annexin A10 expression was observed in 66 (5.8%) of the 1133 patients. Annexin A10 expression was more commonly found in females and was associated with proximal location, ulcerative gross type, advanced T category, N category and TNM stage. CRCs with Annexin A10 expression showed an absence of luminal necrosis, luminal serration and mucin production. CRCs with Annexin A10 expression were associated with CpG island methylator phenotype, microsatellite instability and BRAF mutation. In survival analysis, Annexin A10 expression was associated with poor overall survival and progression-free survival, especially in stage IV CRCs. CONCLUSION: Annexin A10 expression is associated with poor clinical behavior and can be used a supportive surrogate marker of the serrated neoplasia pathway in invasive CRCs. PMID- 26361423 TI - Changes in the spectrum of gastric polyps in the Chinese population. AB - AIM: To evaluate the change in spectrum of gastric polyps in the Chinese population in the past ten years. METHODS: A total of 157902 consecutive patients undergoing esophagogastroduodenoscopy (EGD) from 2004 to 2013 in a tertiary hospital were retrospectively reviewed using an EGD database. Endoscopic records of 4043 patients diagnosed with gastric polyps were recalled for analysis. Data including demographics, information on polyps such as location, pathological diagnosis, reflux esophagitis and Helicobacter pylori infection were obtained. We focused on epithelial polyps, especially hyperplastic polyps, fundic gland polyps and adenomas, and histological classification of specimens from biopsy and endoscopic polypectomy was performed by professional pathologists, based on the updated guidelines. To explore the age distribution of gastric polyps over time, we divided patients with polyps into four groups: A (aged < 30 years), B (aged 30 44 years), C (aged 45-59 years) and D (aged > 60 years). Differences in localization, age, and sex distribution of gastric polyps were analyzed by statistical software. RESULTS: A total of 157902 EGD procedures were performed in ten years at our digestive endoscopy center, of which 4043 cases were diagnosed with gastric polyps confirmed by pathology. There were 2574 (63%) female and 1469 (37%) male patients with an average age of 54.7 years. The overall prevalence of gastric polyps was 2.6% (4043/157902). Our database demonstrated a rising prevalence of gastric polyps over the decade, increasing from 1.0% (80/8025) to 4.70% (828/17787) between 2004 and 2013. There has been a change in the spectrum of gastric polyps with the frequencies of FGPs increasing from 19% (15/80) to 77% (638/828) and hyperplastic polyps decreasing from 65% (52/80) to 15% (123/828). Moreover, data on 1921 polyps in 828 patients diagnosed with gastric polyps in 2013 showed that FGP was the most common type in the current polyp spectrum, making up 81.3% (1562/1921). Location and age distribution of gastric polyps have also altered. The prevalence of polyps located in the antrum decreased from 37.5% (30/80) to 9.30% (77/828), with an increasing prevalence of polyps in the corpus, from 45% (36/80) to 64.25% (532/828). The constituent ratio of older patients (aged > 60 years) in the polyp population decreased from 62.5% (50/80) to 32.13% (266/828), while that of patients aged 45-60 years showed an increased trend. CONCLUSION: There was a shift change in the spectrum of gastric polyps in the Chinese population with altered location and age distribution in the past ten years. PMID- 26361425 TI - Bezoar-induced small bowel obstruction: Clinical characteristics and diagnostic value of multi-slice spiral computed tomography. AB - AIM: To determine the possible predisposing factors of bezoar-induced small bowel obstruction (BI-SBO) and to discuss the diagnostic value of multi-slice spiral computed tomography, particularly contrast-enhanced scanning, in this condition. METHODS: A total of 35 BI-SBO cases treated at our hospital from January 2007 to December 2013 were retrospectively analysed. Complete clinical and computed tomography (CT) data of the patients were available and confirmed by surgery. SBO was clinically diagnosed on the basis of clinical manifestations. Of the 35 patients, 18 underwent abdominal and pelvic CT planar scanning with GE 64-slice spiral CT and 17 underwent abdominal and pelvic CT planar scanning with GE 64 slice spiral CT combined with contrast-enhanced examination. Original images were processed using a GE ADW4.3 workstation to obtain MPR, CPR, MIP and CTA images. The images of all patients were evaluated by two abdominal imaging experts. The main analytical contents of planar scanning included intestinal bezoar conditions, changes in the intestinal wall and changes in peri-intestinal conditions. Vascular hyperaemia and arterial blood supply conditions at a specific obstruction site and the distal end of the obstruction site were evaluated through contrast-enhanced examination. RESULTS: The proportion of males to females among the 35 cases was 1:1.69 (13:22); median age was 63.3 years. The following cases were observed: 29 (82.8%) cases occurred in autumn and winter and showed a history of consuming high amounts of persimmon and hawthorn; 19 (54.3%) cases revealed a history of gastrointestinal surgery; 19 exhibited incomplete dentition, with missing partial or whole posterior teeth; 26 suffered from obstruction at the ileum. A total of 51 bezoars were found in these patients, of whom 16 (45.7%) had multiple bezoars. CT planar scanning of bezoars showed lumps with mottled gas inside the intestinal cavity. Furthermore, 9 cases of bezoars had envelopes and 11 cases were accompanied with thickening of the distal wall of the obstructed bowel. Scanning of 17 cases was enhanced; the results revealed that the mesenteric blood vessels at the obstruction site and the proximal site were dilated, and a total of 7 cases were accompanied with distal vascular dilation and intestinal wall thickening. CONCLUSION: BI-SBO exhibits regional and seasonal characteristics. CT planar and contrast-enhanced scanning can be applied to diagnose and observe vascular conditions in obstructed zones. PMID- 26361424 TI - Thyroid dysfunction in Chinese hepatitis C patients: Prevalence and correlation with TPOAb and CXCL10. AB - AIM: To investigate the relationship among pretreatment serum CXC chemokine ligand 10 (CXCL10), thyroid peroxidase antibody (TPOAb) levels and thyroid dysfunction (TD) in Chinese hepatitis C patients. METHODS: One hundred and thirty nine treatment-naive genotype 1 chronic hepatitis C patients with no history of TD or treatment with thyroid hormones were enrolled in this study. Patients underwent peginterferon alfa-2a/ribavirin (PegIFNalpha-2a/RBV) treatment for 48 wk, followed by detection of clinical factors at each follow-up point. Hepatitis C virus (HCV) antibodies were analyzed using microsomal chemiluminescence, and serum HCV RNA was measured by real-time PCR assay at 0, 4, 12, 24 and 48 wk after the initiation of therapy and 24 wk after the end of therapy. To assess thyroid function, serum thyroid stimulating hormone (TSH), free thyroxine (FT4), free triodothyronine (FT3) and TPOAb/thyroglobulin antibody (TGAb) levels were determined using chemiluminescent immunoassays every 3 mo. Serum CXCL10 levels were determined at baseline. RESULTS: The prevalence of TD was 18.0%. Twenty-one (84.0%) out of twenty-five patients exhibited normal thyroid function at week 24 after therapy. The rate of sustained virological response to PegIFNalpha-2a/RBV in our study was 59.0% (82/139), independent of thyroid function. Pretreatment serum CXCL10 levels were significantly increased in patients with euthyroid status compared with patients with TD (495.2 +/- 244.2 pg/mL vs 310.0 +/- 163.4 pg/mL, P = 0.012). Patients with TD were more frequently TPOAb-positive than non TD (NTD) patients (24.2% vs 12.3%, P = 0.047) at baseline. Three of the one hundred and fifteen patients without TPOAb at baseline developed TD at the end of treatment (37.5% vs 2.6%, P = 0.000). Female patients exhibited an increased risk for developing TD compared with male patients (P = 0.014). CONCLUSION: Lower pretreatment serum CXCL10 levels are associated with TD, and TD prevalence increases in female patients and patients who are positive for TPOAb at baseline. PMID- 26361426 TI - Diffusion-weighted magnetic resonance imaging without bowel preparation for detection of ulcerative colitis. AB - AIM: To evaluate the accuracy of diffusion-weighted imaging (DWI) without bowel preparation, the optimal b value and the changes in apparent diffusion coefficient (ADC) in detecting ulcerative colitis (UC). METHODS: A total of 20 patients who underwent 3T magnetic resonance imaging (MRI) without bowel preparation and colonoscopy within 24 h were recruited. Biochemical indexes, including C-reactive protein (CRP), erythrocyte sedimentation rate, hemoglobin, leucocytes, platelets, serum iron and albumin, were determined. Biochemical examinations were then performed within 24 h before or after MR colonography was conducted. DWI was performed at various b values (b = 0, 400, 600, 800, and 1000 s/mm(2)). Two radiologists independently and blindly reviewed conventional- and contrast-enhanced MR images, DWI and ADC maps; these radiologists also determined ADC in each intestinal segment (rectum, sigmoid, left colon, transverse colon, and right colon). Receiver operating characteristic (ROC) analysis was performed to assess the diagnostic performance of DWI hyperintensity from various b factors, ADC values and different radiological signs to detect endoscopic inflammation in the corresponding bowel segment. Optimal ADC threshold was estimated by maximizing the combination of sensitivity and specificity. MR findings were correlated with endoscopic results and clinical markers; these findings were then estimated by ROC analysis. RESULTS: A total of 100 segments (71 with endoscopic colonic inflammation; 29 normal) were included. The proposed total magnetic resonance score (MR-score-T) was correlated with the total modified Baron score (Baron-T; r = 0.875, P < 0.0001); the segmental MR score (MR score-S) was correlated with the segmental modified Baron score (Baron-S; r = 0.761, P < 0.0001). MR-score-T was correlated with clinical and biological markers of disease activity (r = 0.445 to 0.831, P < 0.05). MR-score-S > 1 corresponded to endoscopic colonic inflammation with a sensitivity of 85.9%, a specificity of 82.8% and an area under the curve (AUC) of 0.929 (P < 0.0001). The accuracy of DWI hyperintensity was significantly greater at b = 800 than at b = 400, 600, or 1000 s/mm(2) (P < 0.05) when endoscopic colonic inflammation was detected. DWI hyperintensity at b = 800 s/mm(2) indicated endoscopic colonic inflammation with a sensitivity of 93.0%, a specificity of 79.3% and an AUC of 0.867 (P < 0.0001). Quantitative analysis results revealed that ADC values at b = 800 s/mm(2) differed significantly between endoscopic inflamed segment and normal intestinal segment (1.56 +/- 0.58 mm(2)/s vs 2.63 +/- 0.46 mm(2)/s, P < 0.001). The AUC of ADC values was 0.932 (95% confidence interval: 0.881-0.983) when endoscopic inflammation was detected. The threshold ADC value of 2.18 * 10(-3) mm(2)/s indicated that endoscopic inflammation differed from normal intestinal segment with a sensitivity of 89.7% and a specificity of 80.3%. CONCLUSION: DWI combined with conventional MRI without bowel preparation provides a quantitative strategy to differentiate actively inflamed intestinal segments from the normal mucosa to detect UC. PMID- 26361427 TI - Cavernous hemangioma of adult pancreas: A case report and literature review. AB - Pancreatic hemangioma is a rare type of benign vascular tumor. Low clinical suspicion and inability of current cross sectional imaging techniques to differentiate it from other pancreatic lesions, contribute to the difficulty in making the correct diagnosis. Without a definitive diagnosis, and due to concern for malignancy, in many instances, surgery is performed. We report a case of pancreas cavernous hemangioma in an 18-year-old female. The patient presented with three-month history of epigastric pain. Physical examination and routine blood tests were normal. Abdominal Computed Tomography scan revealed a 5 cm * 6 cm complex non-enhancing cystic mass in the head of pancreas. Magnetic resonance imaging, endoscopic ultrasonography (EUS) and EUS guided fine needle aspiration cytology were non-diagnostic. Because of uncontrolled symptoms, the patient underwent surgical resection. Histopathology and Immunohistochemical staining confirmed the diagnosis of cavernous hemangioma of pancreas. PMID- 26361428 TI - Single skip metastasis in sentinel lymph node: In an early gastric cancer. AB - Lymph node status is considered a key prognostic and predictive factor in patients with gastric cancer (GC). Although there is a practical approach to the intraoperative detection of sentinel lymph nodes (SLNs), such a procedure is not included in the European surgical protocol. In this report, we present a practical approach to SLN mapping in a representative case with early gastric cancer (EGC). A 74-year-old female was hospitalized with an endoscopically observed, superficially ulcerated tumor located in the antral region. Subtotal gastrectomy with D2 lymphadenectomy and SLN mapping was performed by injecting methylene blue dye into the peritumoral submucosal layer. An incidentally detected blue-stained lymph node located along the middle colic artery was also removed. This was detected 40 min after injection of the methylene blue. Histopathologic examination showed a pT1b-staged well-differentiated HER-2 negative adenocarcinoma. All of the 41 LNs located at the first, third, and fifth station of the regional LN compartments were found to be free of tumor cells. The only lymph node with metastasis was located along the middle colic artery and was considered a non-regional lymph node. This incidentally identified skip metastasis indicated stage IV GC. A classic chemotherapy regimen was given, and no recurrences were observed six months after surgery. In this representative case, low-cost SLN mapping, with a longer intraoperative waiting time, totally changed the stage of the tumor in a patient with EGC. PMID- 26361429 TI - IgG4-unrelated type 1 autoimmune pancreatitis. AB - A 50-year-old male was referred to our hospital for the evaluation of hyperproteinemia. Fluorodeoxyglucose positron emission tomography revealed high fluorodeoxyglucose uptake in the pancreas, bilateral lacrimal glands, submandibular glands, parotid glands, bilateral pulmonary hilar lymph nodes, and kidneys. Laboratory data showed an elevation of hepatobiliary enzymes, renal dysfunction, and remarkably high immunoglobulin (Ig) G levels, without elevated serum IgG4. Abdominal computed tomography revealed swelling of the pancreatic head and bilateral kidneys. Endoscopic retrograde cholangiopancreatography showed an irregular narrowing of the main pancreatic duct in the pancreatic head and stricture of the lower common bile duct. Histological examination by endoscopic ultrasonography-guided fine-needle aspiration revealed findings of lymphoplasmacytic sclerosing pancreatitis without IgG4-positive plasma cells. Abnormal laboratory values and the swelling of several organs were improved by the treatment with steroids. The patient was diagnosed as having type 1 autoimmune pancreatitis (AIP) based on the International Consensus Diagnostic Criteria. Therefore, we encountered a case of compatible type 1 AIP without elevated levels of serum IgG4 or IgG4-positive plasma cells. This case suggests that AIP phenotypes are not always associated with IgG4. PMID- 26361430 TI - Perforated appendiceal diverticulitis associated with appendiceal neurofibroma in neurofibromatosis type 1. AB - An appendiceal neurofibroma (ANF) is a rare neoplasm associated with neurofibromatosis type 1(NF-1), an inheritable neurocutaneous disorder that involves multiple systems including the intraabdominal organs. Appendiceal diverticulitis occasionally ruptures in the absence of intense abdominal pain, which can lead to serious consequences. Recent reports highlight the association between appendiceal diverticulum and appendiceal neoplasms; however, there is still little information on the association between appendiceal diverticulitis and ANF in NF-1. A 51-year-old Japanese male with NF-1 was referred to the division of surgery for mild right lower quadrant pain. It was suspected he had perforated acute appendicitis with periappendiceal abscess based on clinical manifestations and findings of computed tomography. An emergency appendectomy was conducted. The pathological examination revealed diffusely proliferated tumor cells of a neurofibroma, coexistent with multiple appendiceal diverticulums, leading to the diagnosis of perforated appendiceal diverticulitis associated with ANF. Although he developed a remnant abscess, he recovered with the conservative treatments of antibiotics and drainage. This case suggests that appendiceal diverticulitis might be a complication of appendiceal involvement of NF-1, and that it occasionally ruptures in the absence of intense abdominal pain. Clinicians should recognize that NF-1 can cause various abdominal manifestations. PMID- 26361431 TI - Cutaneous metastasis as an initial presentation of a non-functioning pancreatic neuroendocrine tumor. AB - Non-functioning pancreatic neuroendocrine tumors (NF-PNETs) are rare tumors that account for 2% of all pancreatic malignancy. About 60% of NF-PNETs present distant metastases and usually hepatic metastases. However, cutaneous metastases are very rare. Herein, we report our experience with a 60-year-old male who visited our outpatient clinic with a mass on his left hip. An abdominal computerized tomography scan demonstrated not only a left hip mass and an enlarged left inguinal lymph node, but also a huge heterogeneous enhancing mass on the pancreas. Initially, we removed the metastatic lesions, which was a small cell neuroendocrine carcinoma with 50% of the Ki-67 index in the histopathological report. After 3 wk, we performed a total pancreatectomy and a total gastrectomy. Four weeks after the 1(st) operation, we detected a recurrence at the operative bed on his left hip, and subsequently removed the recurring mass. The patient was receiving chemotherapy based on etoposide and cisplatin treatment. PMID- 26361432 TI - Giant liposarcoma of the esophagus: A case report. AB - Liposarcomas rarely develop in the aerodigestive tract. Here, we present a primary esophageal liposarcoma that was discovered between the T3 and T7 levels of the esophagus during right pleural exploration of a 51-year-old male patient. The patient had presented with non-specific symptoms, including progressive dysphagia over the previous 6 mo, without complaints of chest or epigastric pain, regurgitation, or weight loss. A radical three-hole esophagectomy was performed. The tumor was extremely large (14 cm * 7.0 cm * 6.5 cm), but completely encapsulated. Upon histological examination, the tumor was diagnosed as a giant, well-differentiated esophageal liposarcoma with a dedifferentiated component. Non specific radiological and endoscopic results during the clinical work-up delayed diagnosis until post-operative histology was performed. In this report, the clinical, radiological and endoscopic diagnostic challenges specific to the case are discussed, as well as the surgical and pathological findings. PMID- 26361433 TI - Estimating and Identifying Unspecified Correlation Structure for Longitudinal Data. AB - Identifying correlation structure is important to achieving estimation efficiency in analyzing longitudinal data, and is also crucial for drawing valid statistical inference for large size clustered data. In this paper, we propose a nonparametric method to estimate the correlation structure, which is applicable for discrete longitudinal data. We utilize eigenvector-based basis matrices to approximate the inverse of the empirical correlation matrix and determine the number of basis matrices via model selection. A penalized objective function based on the difference between the empirical and model approximation of the correlation matrices is adopted to select an informative structure for the correlation matrix. The eigenvector representation of the correlation estimation is capable of reducing the risk of model misspecification, and also provides useful information on the specific within-cluster correlation pattern of the data. We show that the proposed method possesses the oracle property and selects the true correlation structure consistently. The proposed method is illustrated through simulations and two data examples on air pollution and sonar signal studies. PMID- 26361434 TI - Factors contributing to reduced caregiver strain in a publicly-funded child mental health system. AB - This study examined caregiver strain in families who initiated mental health services for their child. Predictors of strain and the bidirectional relation between strain and child symptoms were examined. Participants included 218 children ages 4-13 with disruptive behavior problems and their caregivers, plus 96 psychotherapists, recruited from six publicly-funded clinics. Child disruptive behavior severity and caregiver strain were assessed at baseline, four, and eight months. Multilevel models were used to examine predictors of reduced caregiver strain, and autoregressive cross-lagged models were used to examine the bidirectional relations between change in caregiver strain and behavior problems over time. There were small to medium decreases in caregiver strain over the eight months after the initiation of mental health services, but few factors predicted change other than initial behavior problem severity. While more severe initial child symptoms predicted greater reductions in caregiver strain, greater child symptom severity sustained at four months predicted lesser improvements in caregiver strain. Simultaneously, greater caregiver strain predicted less improvement in child symptom severity, suggesting that child symptom severity and caregiver strain impact each other over time. These results suggest that attending to both child and caregiver factors may be important in maintaining improvements after initiating usual care. PMID- 26361435 TI - Development of Human Posture Simulation Method for Assessing Posture Angles and Spinal Loads. AB - Video-based posture analysis employing a biomechanical model is gaining a growing popularity for ergonomic assessments. A human posture simulation method of estimating multiple body postural angles and spinal loads from a video record was developed to expedite ergonomic assessments. The method was evaluated by a repeated measures study design with three trunk flexion levels, two lift asymmetry levels, three viewing angles and three trial repetitions as experimental factors. The study comprised two phases evaluating the accuracy of simulating self and other people's lifting posture via a proxy of a computer generated humanoid. The mean values of the accuracy of simulating self and humanoid postures were 12 degrees and 15 degrees , respectively. The repeatability of the method for the same lifting condition was excellent (~2 degrees ). The least simulation error was associated with side viewing angle. The estimated back compressive force and moment, calculated by a three dimensional biomechanical model, exhibited a range of 5% underestimation. The posture simulation method enables researchers to simultaneously quantify body posture angles and spinal loading variables with accuracy and precision comparable to on screen posture matching methods. PMID- 26361436 TI - Improved body composition assessment using biceps skinfold and physical activity score in premenarcheal girls: a DXA-based validation study. AB - OBJECTIVE: Age-specific body mass index (BMI) is commonly employed as an index of adiposity for pediatric clinical and research purposes. However, BMI fails to discriminate between fat and lean mass, making it an imperfect monitor for obesity. We hypothesized that simple anthropometry and organized non-aquatic physical activity assessment (PA) would provide superior explanatory value for pediatric body composition outcomes. RESEARCH METHODS AND PROCEDURES: In a cross sectional analysis, whole body DXA assessed body composition in 120 pre menarcheal girls. Questionnaires were used to record and generate annual means for PA. Age, Tanner breast self-stage, height, weight, BMI, skinfold thicknesses, girths and PA were examined as potential predictors of body composition outcomes, using backward stepwise multiple linear regression. A parsimonious regression model was developed in 75% and cross-validated in 25% of the total sample; models were rerun with the total sample. RESULTS: Subject means were as follows: age = 10.4+/-1.2 y; lean soft tissue (LST) = 24.4+/-4.2 kg; fat mass (FM) = 8.1+/-4.1 kg; BMI = 17.6+/-2.5 kg/m2; PA = 6.8+/-5.0 h/wk; Tanner breast self-stage ranged from 1 to 3. BMI for age Z scores ranged from -2 to 2.1. Age and BMI alone yielded adjusted model r2=0.44 to 0.78. The final model, including age, height, weight, biceps skinfold and PA, yielded adjusted r2=0.61 to 0.92, P <0.001. Prediction of LST and FM increased from r2=0.64 and 0.76 to r2=0.92 and 0.91, respectively. DISCUSSION: Compared to BMI and age alone, models including biceps skinfold, PA, height, weight and age had superior explanatory value for clinically-relevant body composition outcomes, and are feasible for clinical use. PMID- 26361437 TI - Reverse Shoulder Arthroplasty in the United States: A Comparison of National Volume, Patient Demographics, Complications, and Surgical Indications. AB - BACKGROUND: Shoulder arthroplasty is increasing in the United States. Reverse shoulder arthroplasty (RSA) has emerged as an alternative treatment for end-stage glenohumeral pathology. Until recently, administrative coding practices have not differentiated RSA from traditional total shoulder arthroplasty (TSA), and thus national procedural volume has been unknown. The purpose of this study was to define the utilization, patient characteristics, indications and complications for RSA, and contrast these to TSA and hemiarthroplasty (HA). METHODS: The 2011 Nationwide Inpatient Sample (HCUP-NIS) dataset was queried using ICD-9-CM codes to identify patients undergoing RSA, TSA, or HA. We used weighted estimates of national procedure volume, per-capita utilization, patient comorbidities, and inpatient complications denned by the Agency for Healthcare Research and Quality (AHRQ) and identified them using standard methods described by Elixhauser. ANOVA statistical analysis was used and significance was denned as p value <0.05. RESULTS: In 2011, 66,485 patients underwent shoulder arthroplasty; there were 21,692 cases of RSA, 29,359 of TSA, and 15,434 of HA. Utilization of RSA and TSA increased between 2002-2011, and decreased for HA. RSA patients were older (72.7 years vs 67.4 TSA vs 66.8 HA) and more commonly female. Comorbidity burden was highest in patients undergoing HA. Inpatient complications were highest after RSA (p < 0.001). When compared to TSA, RSA was more commonly used in the setting of rotator cuff disease, and posttraumatic sequelae (p<0.001). CONCLUSIONS: Our findings represent the first national estimates of RSA within the United Sates. RSA is a significant contributor to increasing shoulder arthroplasty utilization nationally representing one-third of arthroplasty cases. Conditions traditionally managed with HA in older populations appear to now be more commonly managed with RSA. RSA is performed on older patients with expanded indications. PMID- 26361438 TI - Outcomes Following Suture-Anchor Repair of Pectoralis Major Tears: A Case Series and Review of the Literature. AB - BACKGROUND: Rupture of the pectoralis major muscle (PMM) is an uncommon injury that occurs during physical exercise and high-impact contact sports; it may result in pain, weakness, and disability. Surgical repair is currently the preferred treatment of PMM rupture. Our study assesses subjective and functional outcomes of patients following repair of acute and chronic PMM ruptures. METHODS: Retrospective review identified twenty patients who underwent PMM repair by the senior author (BRW) between 2003 and 2011. Injury and surgical data was reviewed for all 20 patients. Six patients were assessed minimum 1-year post operatively for clinical outcomes, (SF-36, DASH, and ASES), physical exam (ROM & cosmesis), and Cybex isokinetic strength testing. RESULTS: All patients were men with an average age of 30 years (range 20-55) at time of injury. The average time from injury to surgical repair was 3.8 months (range <1-28 months), and average follow up was 16.5 months (range 0-99). The majority of patients suffered injury while bench pressing (12/20; 60%) or wrestling (3/20; 15%). The most common intra operative findings were partial sternal tears (9/20; 45%) followed by complete sternal tears (4/20; 20%). Six (30%) of twenty patients consented for on-site follow-up and clinical assessment. Average preoperative physical component scores from SF-36 improved from 43 (range 37.8-52.7) to 53.1 (range 48.1-55.8) at follow up. Average preoperative DASH scores decreased from 74 points (range 68.7-83.3) to 5.3 points (range 1.7-8.3) at follow-up. Average pre-operative ASES scores improved from 82.8 points (range 71.7-96.7) to 96.7 points (range 91.7-98.3) at follow up. Average isokinetic strength deficiency in horizontal adduction at 60 degrees /s was 15% (range 16%-29%) and average at 120 degrees /s was 9% (range 2% 21%). According to the Bak criteria, overall results were excellent in two patients (33%), good in two (33%), while two (33%) had a fair result. CONCLUSION: Surgical repair of PMM rupture by suture anchor fixation provides high patient satisfaction and predictable return of strength, cosmesis, and overall function. Suture anchor fixation produced similar clinical outcomes and return of strength when compared to other surgical repair methods. Our results demonstrate isokinetic strength deficiency similar to historical results. LEVEL OF EVIDENCE: Level 4: Retrospective Case Series. PMID- 26361439 TI - A Finite Element Analysis of Medial Patellofemoral Ligament Reconstruction. AB - BACKGROUND: The medial patellofemoral ligament is the primary soft-tissue restraint to lateral patella translation. Medial patellofemoral ligament reconstruction has become a viable surgical option to provide patellar stability in patients with recurrent instability. The primary goal of this study was to determine the effect of medial patellofemoral ligament reconstruction on the lateral force-displacement behavior of the patella using finite element analyses. METHODS: A finite element model of the knee was created using cadaveric image data. Experimental testing was performed to validate the computational model. After validation, the model was modified to study the effect of various medial patellofemoral ligament reconstruction insertion sites, allowing comparison of patellofemoral contact force and pressure. RESULTS: For the intact anatomic model, the lateral restraining force was 80.0 N with a corresponding patellar contact area of 54.97 mm(2). For the anatomic reconstructed medial patellofemoral ligament model, the lateral restraining force increased to 148.9 N with a contact area of 71.78 mm(2). This compared favorably to the corresponding experimental study. The force required to laterally displace the patella increased when the femoral insertion site was moved anteriorly or distally. The lateral restraining force decreased when the femoral insertion site moved proximally and the patellar insertion site moved either proximal or distal by 5 mm. CONCLUSION: The line of action was altered with insertion site position, which in turn changed the amount of force it took to displace the patella laterally. Considering the model constraints, an anterior femoral attachment may over constrain the patella and increase cartilage wear due to increase contact area and restraining force. CLINICAL RELEVANCE: A malpositioned femoral tunnel in MPFL reconstruction could increase restraining forces and PF contact pressure, thus it is suggested to use intra-operative fluoroscopy to confirm correct tunnel placement. PMID- 26361440 TI - Posterolateral Knee Reconstruction Versus Repair. AB - BACKGROUND: Recent literature has shown that posterolateral corner injuries of the knee have poor results when treated with repair, when compared to reconstruction. Our study sought to compare outcomes of posterolateral knee injuries treated with repair versus reconstruction and report results from our institution, with the hypothesis that acute repairs have comparable results to reconstructions. METHODS: We identified patients with posterolateral knee reconstruction or repair from January 1, 2000 to March 1, 2012. Patients returned for outcome measures, clinical exam and varus stress radiographs. Further, each patient underwent a chart review. Varus stress radiographs were obtained in 20 control knees, with no history of knee trauma, to our two cohort groups. RESULTS: 26 knees in 25 patients (17 reconstructions and 9 repairs) were evaluated in clinic at mean of 42 months postoperatively for repairs and 38 months postoperatively for reconstructions. Average IKDC scores for reconstruction and repair were 68 and 71, respectively. Average Lysholm scores for these groups were 83 for reconstructions and 83 for repairs. No statistically significant differences existed. Average varus gapping at zero degrees was 8.21 and 8.84 millimeters (mm) for reconstructions and repairs, respectively. Average varus gapping at 20 degrees knee flexion was 11.25 mm for reconstructions and 10.34 mm for repairs. No statistically significant differences were observed in varus gapping between the two groups. Each patient chart was reviewed for complications. There were 2 failures in the 44 patient reconstruction group (4.7%) and 2 failures in the 18 patient repair group (11.1%). We noted a high rate (10/19 patients) of primarily distally-based injuries in our repair group. All failures were treated with revision reconstructions. CONCLUSION: We found low failure rates in both groups. All knees in the repair group were operated within three weeks of injury. Our repair knees had a high rate of distally based avulsion and, were felt to have acceptable tissue that could be successfully repaired. We recommend posterolateral knee repair in cases with distally based avulsions that can be operatively treated within 3 weeks of injury, and have good tissue quality at the time of surgery. LEVEL OF EVIDENCE: IV. PMID- 26361441 TI - Medial Patella Subluxation: Diagnosis and Treatment. AB - Medial patella subluxation is a disabling condition typically associated with previous patellofemoral instability surgery. Patients often describe achy pain with painful popping episodes. They often report that the patella shifts laterally, which occurs as the medial subluxed patella dramatically shifts into the trochlear groove during early knee flexion. Physical examination is diagnostic with a positive medial subluxation test. Nonoperative treatment, such as focused physical therapy and patellofemoral stabilizing brace, is often unsuccessful. Primary surgical options include lateral retinacular repair/imbrication or lateral reconstruction. Prevention is key to avoid medial patella subluxation. When considering patellofemoral surgery, important factors include appropriate lateral release indications, consideration of lateral retinacular lengthening vs release, correct MPFL graft placement and tension, and avoiding excessive medialization during tubercle transfer. This review article will analyze patient symptoms, diagnostic exam findings and appropriate treatment options, as well as pearls to avoid this painful clinical entity. PMID- 26361442 TI - Effectiveness of Fulkerson Osteotomy with Femoral Nerve Stimulation for Patients with Severe Femoral Trochlear Dysplasia. AB - BACKGROUND: Patients with femoral trochlear dysplasia are at risk for chronic recurrent patellofemoral dislocations, with extreme cases often requiring a surgical procedure. Anteromedialization of the tibial tubercle with intraoperative femoral nerve stimulation and concurrent medial patella-femoral ligament (MPFL) reconstruction is a previously reported method of maximizing patello-femoral congruency. We hypothesize the Fulkerson osteotomy with intraoperative femoral nerve stimulation and concurrent MPFL reconstruction in patients with severe trochlear dysplasia provides equivalent postoperative clinical outcomes to the same procedure in patients with low level trochlear dysplasia. METHODS: 48 knees underwent Fulkerson osteotomy with intraoperative femoral nerve stimulation and concurrent MPFL reconstruction for recurrent lateral patellar dislocations. MRI, surgeon intraoperative assessment, and X-ray were used to assess degrees of trochlear dysplasia; inter-observer and intra observer error were measured. The knees positive for severe dysplasia on MRI, intraoperative assessment, and X-ray were considered as a comparison cohort to the rest of the study population. We considered postoperative dislocation events and patellar tracking kinematics as outcome measures. Independent student t tests and Fisher exact tests were used to evaluate differences between groups. Significance was set at P<0.05. RESULTS: 11 knees were positive for severe dysplasia (SD) by combined MRI, surgeon intraoperative assessment, and X-ray with the remaining 37 knees categorized as low dysplasia (LD). No patients in either group exhibited apprehension or required re-operation. Mean sulcus angle in the SD group was 175.8 +-2.45 degrees (95% CI 171.0-180.6); the LD group mean sulcus angle was 154.3 +- 0.98 degrees (95% CI 152.4-156.2) (P<.001). Postoperatively there was no significant difference in dislocation events between the SD group (0/11) and the LD group (2/37) (P>0.999). Patellar maltracking decreased in both groups and there were no significant differences in estimates of patellofemoral congruency between the SD (2/11) and LD (8/37) (P>0.999) groups. CONCLUSION: The Fulkerson osteotomy with femoral nerve stimulation aimed at maximizing patellofemoral congruency may be an equally effective procedure for patients with either severe or mild trochlear dysplasia. LEVEL OF EVIDENCE: Level III, Retrospective comparative study. PMID- 26361443 TI - Dysplasia Epiphysealis Hemimelica Treated with Osteochondral Allograft: A Case Report. AB - BACKGROUND: Dysplasia epiphysealis hemimelica (DEH), or Trevor's disease, is a developmental disorder of the pediatric skeleton characterized by asymmetric osteochondral overgrowth. METHODS: We present the case of a five year old boy with a two year history of right knee pain and evidence of DEH on imaging who underwent initial arthroscopic resection of his lesion with subsequent recurrence. The patient then underwent osteochondral allograft revision surgery and was asymptomatic at two year follow-up with a congruent joint surface. RESULTS: To our knowledge, this is the first reported case of a DEH lesion treated with osteochondral allograft and also the youngest reported case of osteochondral allograft placement in the literature. CONCLUSIONS: Osteochondral allograft may be a viable option in DEH and other deformities of the pediatric knee. LEVEL OF EVIDENCE: Level V. PMID- 26361444 TI - Assessing Lower Limb Alignment: Comparison of Standard Knee Xray vs Long Leg View. AB - BACKGROUND: High tibial osteotomy (HTO) is a well-established and commonly utilized technique in medial knee osteoarthritis secondary to varus malalignment. Accurate measurement of the preoperative limb alignment, and the amount of correction required are essential when planning limb realignment surgery. The hip knee-ankle angle (HKA) measured on a full length weightbearing (FLWB) X-ray in the standing position is considered the gold standard, since it allows for reliable and accurate measurement of the mechanical axis of the whole lower extremity. In general practice, alignment is often evaluated on standard anteroposterior weightbearing (APWB) X-rays, as the angle between the femur and tibial anatomic axis (TFa). It is, therefore, of value to establish if measuring the anatomical axis from limited APWB is an effective measure of knee alignment especially in patients undergoing osteotomy about the knee. METHODS: Three independent observers measured preoperative and postoperative FTa with standard method (FTa1) and with circles method (FTa2) on APWB X-ray and the HKA on FLWB X ray at three different time-points separated by a two-week period. Intra-observer and inter-observer reliabilities and the comparison and relationship between anatomical and mechanical alignment were calculated. RESULTS: Intra- and interclass coefficients for all the three methods indicated excellent reliability, having all the values above 0.80. Using the mean of paired t-student test, the comparison of HKA versus TFa1 and TFa2 showed a statistically significant difference (p<.0001) both for the pre-operative and post-operative sets of values. The correlation between the HKA and FTal was found poor for the preoperative set (R=0.26) and fair for the postoperative one (R=0.53), while the new circles method showed a higher correlation in both the preoperative (R=0.71) and postoperative sets (R=0.79). CONCLUSIONS: Intra-observer reliability was high for HKA, FTal and FTa2 on APWB x-rays in the pre- and post-operative setting. Inter-rater reliability was higher for HKA and TFa2 compared to FTal. The femoro tibial angle as measured on APWB with the traditional method (FTal) has a weak correlation with the HKA, and based on these findings, should not be used in everyday practice. The FTa2 showed better correlation with the HKA, although not excellent. LEVEL OF EVIDENCE: Level III, Retrospective study. PMID- 26361446 TI - Expedited Operative Care of Hip Fractures Results in Significantly Lower Cost of Treatment. AB - BACKGROUND: There are an estimated 150,000 hip fractures per year in the United States, with estimated costs of care between $10.3 billion and $15.2 billion. With such high costs and an increasing burden of care, there has been interest in newer methods to increase efficiency of care. One such method is expedited fracture care, with earlier operative intervention. The purpose of this study was to determine if intervention within six hours of admission decreased costs with no change in the rate of major complications. METHODS: A retrospective review of all patients age >65 undergoing operative intervention for a proximal femur fracture over a two year period were identified. Patients were divided into two groups: those undergoing operative intervention < six hours after admission (early) and those undergoing operative intervention > six hours after admission. Patient age, average length of stay, and complication rates were determined for the two groups. RESULTS: Our study identified 657 patients, 111 of which underwent early intervention with the remaining 546 undergoing late intervention. The average length of stay for the early intervention group was 4.11 days, compared to 5.68 days for die late intervention group (p=0.0005). There was a significant difference in average cost between the two groups. The average cost of the early intervention was $49,900, with the average cost of late intervention being $65,300 (p = 0.0086). There was no significant difference in incidence of major complications between the two groups. CONCLUSION: Programs emphasizing early intervention for hip fractures have the potential for large healthcare savings, with an average savings of $15,400. LEVEL OF EVIDENCE: Level IV, therapeutic case series. PMID- 26361445 TI - Fractures Due to Gunshot Wounds: Do Retained Bullet Fragments Affect Union? AB - BACKGROUND: Many types of projectiles, including modern hollow point bullets, fragment into smaller pieces upon impact, particularly when striking bone. This study was performed to examine the effect on time to union with retained bullet material near a fracture site in cases of gunshot injury. METHODS: All gunshot injuries operatively treated with internal fixation at a Level 1 Trauma Center between March 2008 and August 2011 were retrospectively reviewed. Retained bullet load near the fracture site was calculated based on percentage of material retained compared to the cortical diameter of the involved bone. Analyses were performed to assess the effect of the lead-cortical ratio and amount of comminution on time to fracture union. RESULTS: Thirty-two patients (34 fractures) met the inclusion criteria, with an equal number of comminuted (17) and non-comminuted fractures (17). Seventeen of 34 fractures (50%) united within 4 months, 16/34 (47%) developed a delayed union, and 1/34 (3%) developed a nonunion requiring revision surgery. Sixteen of 17 fractures (94%) that united by 4 months had a cumulative amount of bullet fragmentation retained near the fracture site of less than 20% of the cortical diameter. Nine out of 10 fractures (90%) with retained fragments near the fracture site was equal to or exceeding 20% of the cortical diameter had delayed or nonunion. Fracture comminution had no effect on time to union. CONCLUSIONS: The quantity of retained bullet material near the fracture site was more predictive of the rate of fracture union than was comminution. Fractures with bullet fragmentation equal to or exceeding 20% of the cortical width demonstrated a significantly higher rate of delayed union/nonunion compared to those fractures with less retained bullet material, which may indicate a local cytotoxic effect from lead on bone healing. These findings may influence decisions on timing of secondary surgeries. LEVEL OF EVIDENCE: Level III. PMID- 26361447 TI - Outcomes Following Low-Energy Civilian Gunshot Wound Trauma to the Lower Extremities: Results of a Standard Protocol at an Urban Trauma Center. AB - BACKGROUND: Lower extremity injuries secondary to low-energy gunshot wounds are frequently seen in the civilian populations of urban areas. Although these wounds have fewer complications than high-energy gunshot injuries, the functional and psychological damage is still significant making appropriate timely orthopaedic treatment and follow-up imperative. PURPOSE: The purpose of this study is to present our outcomes in the treatment of low-energy gunshot wounds in a civilian population at an urban, level one trauma center in patients treated by a standard protocol. METHODS: One hundred and thirty three patients who sustained 148 gunshot wound injuries were treated at our level one trauma center between January 1(st), 2009 and October 1(st), 2011. Following IRB approval, we extracted information from medical records regarding hospital course, length of stay and type of operative or non-operative treatment. If available, injury and post operative radiographs were also reviewed. Patients were contacted by telephone to obtain Short Musculoskeletal Function Assessment (SMFA) surveys, pain on a scale of 0-10 and for the determination of any adverse events related to their shooting. RESULTS: There were 125 men (94.0%) and 8 women (6.0%) with an average age of 27.1 years (range 15.2-56.3). Seventy-six patients (57.1%) did not have any health insurance upon admission. The average length of stay in the hospital was 4.5 days (range 0.0-88.0). Fifty-one gun shots (34.5%) resulted in fractures of the lower extremities. Patients underwent a total of 95 lower extremity related procedures during their hospitalization. Twenty-two patients (16.5%) experienced a complication related to their gunshot wounds. 38% of the cohort was available for long-term functional assessment At a mean 23.5 months (range 8-48) of follow up, patients reported mean Functional and Bothersome SMFA scores of 19.6 (SD 15.9) and 10.9 (SD 15.6) suggesting that these patients have poorer function scores than the general population. These patients still had pain related to their gunshot injury with an average pain score of 2.16 (range 0-8). CONCLUSIONS: Gunshot injuries to the extremities may involve bone, soft tissue, and neurovascular structures. Execution of appropriate therapeutic methods in such situations is critical for treating surgeons given the potential for complications. At our level one trauma center, gunshot victims were predominantly young, uninsured adult men. Complications included infection, compartment syndrome, and arterial injuries. Functional data collected demonstrated that patients continued to have difficulties with ADL's at long-term follow-up. PMID- 26361448 TI - Asymmetric Bilateral Hip Dislocations: A Case Report and Historical Review of the Literature. AB - BACKGROUND: Asymmetric bilateral hip dislocations are a rare injury pattern in which one hip dislocates posteriorly, and the contralateral hip dislocates anteriorly. We report a case of bilateral asymmetric hip dislocations and provide a comprehensive review of all available reports, identifying 104 total cases, which is 70 more than previously reported. PURPOSE: To review and evaluate the total body of literature regarding bilateral asymmetric hip dislocations. METHODS: Comprehensive literature review and analysis of all reports of bilateral asymmetric hip dislocations with concurrent case report. RESULTS AND CONCLUSIONS: Bilateral, asymmetric represent approximately 0.01%-0.02% of all joint dislocations. There has been a substantial increase in the number of case reports in the literature in the last 10 years. Males are more likely than females to incur this injury pattern and the most common mode of injury is motor vehicle accident Urgent closed reduction should be attempted in an efficient and safe manner to avoid potential complications, and open reduction should be considered in irreducible dislocations. Post reduction management should include stability assessment and CT to assess for associated injuries and intraarticular fragments; although no clear guidelines for post-reduction treatment emerged. Common complications include: nerve palsies, AVN and heterotopic ossification. PMID- 26361449 TI - Impact of Age, Gender and Anesthesia Modality on Post-Operative Pain in Total Knee Arthroplasty Patients. AB - BACKGROUND: Optimizing pain control following total knee arthroplasty is of utmost importance to the immediate post-operative course. Various anesthesia modalities are available, but studies comparing multiple anesthesia modalities, patient age, and sex are limited. QUESTIONS/PURPOSE: The purpose of our study was to examine the impact of patient age, gender, and perioperative anesthesia modality on postoperative pain following primary total knee arthroplasty. METHODS: 443 patients who underwent primary total knee arthroplasty by 14 surgeons with some combination of general anesthesia, spinal anesthesia, femoral nerve block, and intrathecal morphine were identified. Anesthesia route and type, length of surgery, post-operative patient-reported pain measures using the Visual Analog Scale, opioid consumption, and length of hospital stay were recorded for each patient and used to compare differences among study groups. RESULTS: No significant differences were noted between anesthesia groups with regards to postoperative pain or length of hospital stay. Patients receiving spinal anesthesia and femoral nerve block without intrathecal morphine were significantly older than other groups. Patients receiving general anesthesia required significantly more daily intravenous morphine equivalents than patients receiving spinal anesthesia. Patients receiving spinal anesthesia with femoral nerve block and intrathecal morphine consumed the least amount of morphine equivalents. When comparing males and females among all groups, females had significantly higher pain ratings between 24-36 and 24-48 hours postoperatively. CONCLUSION: Although no significant differences were noted on pain scores, patients who received spinal anesthesia with intrathecal morphine and femoral nerve block used less narcotic pain medication than any other group. Females reported significantly higher pain between 24-48 hours post-op compared with males but not significantly greater anesthetic usage. LEVEL OF EVIDENCE: Level III, Therapeutic Study, (Retrospective Comparative study). PMID- 26361450 TI - Protrusio After Medial Acetabular Wall Breach in Total Hip Arthroplasty. AB - BACKGROUND: Medial protrusio is a recognized complication of total hip arthroplasty, but it is not known if a medial wall breach during cup implantation increases the risk. We thus investigated the effect of up to a 2 cm defect in the medial acetabular wall in a cadaveric model. Separately, we investigated the ability of acetabular screws to rescue the construct. METHODS: Nine human fresh frozen hemipelves were reamed medially to create the defect, implanted with acetabular cups, and then loaded to failure. The nine contralateral hemipelves were reamed in a standard fashion and served as controls. Separately, nine hemipelves with a medial defect were augmented with two acetabular screws each, then loaded to failure, with the contralateral side as a control. Load-to failure, stiffness, and energy were recorded. FINDINGS: The presence of a medial wall defect decreased the load-to-failure by a mean of 26% (5710 v. 4221 N, p=0.024). The addition of two acetabular screws did not rescue the construct (mean 27% decrease, 4082 v. 2985 N, p=0.024). The majority of specimens failed in a supra-physiologic range of force. Bone density correlated with failure loads (R(2) range of 0.54-0.78), and osteoporotic specimens were more likely to fail at a physiologic range, consistent with forces experienced during minor stumbles or falls. INTERPRETATION: Osteoporotic patients with a medial wall defect after hip arthroplasty may be susceptible to fracture during activities of daily living. Protected weight bearing with an assistive device may be reasonable in order to minimize fall risk until cup ingrowth is achieved. PMID- 26361451 TI - Uncemented Porous Tantalum Acetabular Components: Early Follow-Up and Failures in 599 Revision Total Hip Arthroplasties. AB - BACKGROUND: The purpose of this study was to determine the early outcomes of 599 cases of revision THA performed using a porous tantalum cup. METHODS: Clinical and radiographic data was sought in all patients at a minimum two years follow up, after acetabular revision performed with a porous tantalum cup. RESULTS: Of the 599 cases identified, there were 51 re-operations in 47 patients (7.8 percent). Cup removal was required in 14 of these cases (2.3 percent). The most common cause for cup removal was a septic joint (12). No cups were revised for aseptic loosening during the study period. There was one case of early cup migration. There were 17 incomplete lucencies not initially seen on post operative films, but identified later, all were non-progressive on subsequent x rays. CONCLUSIONS: Early results of porous tantalum acetabular components in the revision setting demonstrate good initial stability and low re-operation rates at two years follow-up. LEVEL OF EVIDENCE: Level 4: Case series. PMID- 26361452 TI - Lateral Epicondylitis and Tobacco Use: A Case-Control Study. AB - BACKGROUND: Although lateral epicondylitis (LE) is a very common tendinopathy, we understand little about the etiology of the disease. Tobacco use has been associated with other tendinopathies, and the purpose of this study is to determine if there is an association between the incidence of lateral epicondylitis and tobacco use. METHODS: We performed a retrospective cohort study of adult patients diagnosed with lateral epicondylitis. Patients from a single orthopaedic surgeon's practice with LE were matched to control patients with other common upper extremity conditions based on age, gender, and occupation. A total of 65 case patients and 217 control patients were included in the study. The incidence of smoking in patients with lateral epicondylitis was compared to the incidence of smoking in the control group. RESULTS: Of the LE patients, 30/65 (46.2%) were non-smokers, 23/65 (35.4%) were former smokers, and 12/65 (18.5%) were current smokers. Of the control patients, 121/217 (55.8%) were non-smokers, 45/217 (20.7%) were former smokers, and 51/217 (23.5%) were current smokers. The odds of LE patients being former or current smokers compared to control patients were 1.45 times higher, but this was not statistically significant. Among people who did not smoke at the time of presentation, the odds of being a former smoker were 2.28 times higher in LE patients than in controls, which was statistically significant. CONCLUSIONS: The odds of being a former smoker were significantly higher in patients with lateral epicondylitis compared to patients with other upper extremity conditions. Although it did not reach statistical significance, the odds of being former or current smokers were also higher in the LE group. These results suggest a relationship between smoking history and incidence of lateral epicondylitis, though more research is needed to determine the exact nature of the relationship. LEVEL OF EVIDENCE: Prognostic, Level III. PMID- 26361453 TI - Structures at Risk During Volar Percutaneous Fixation of Scaphoid Fractures: A Cadaver Study. AB - BACKGROUND: Fracture of the scaphoid bone can be treated with cast immobilization or surgery. Historically, surgery was reserved for displaced fractures. However, because weeks of cast immobilization may result in stiffness, loss of strength, loss of bone density and an inability to work or participate in recreational activities for a prolonged period, operative treatment of non-displaced fractures has become increasingly common. Several surgical techniques for fixation have been described, but their risks and benefits have not yet been clearly elucidated. In a study in cadavers, we investigated whether one approach--volar percutaneous fixation--might pose a risk of injury to surrounding structures. METHODS: In 15 cadaver upper limbs with the wrist structures intact, a K-wire was inserted in a volar percutaneous manner under fluoroscopic guidance, distal to proximal and through the scaphoid waist into the center-center position. The volar aspect of the wrist and hand were then dissected around the K-wire, with isolation of surrounding structures. The distance between the K-wire and several individual structures was then measured with use of a digital caliper. RESULTS: The K-wire was at least 4 mm from the superficial radial nerve, the first dorsal extensor compartment, the recurrent motor branch of the median nerve, and the radial artery (RA) in all specimens. However, the K-wire had penetrated die flexor carpi radialis (FCR) tendon in four specimens and was directly adjacent to it in another four. In one specimen, the K-wire was directly adjacent to the superficial volar branch of die RA. CONCLUSIONS: The K-wire may penetrate the FCR tendon and the superficial volar branch of the radial artery during volar percutaneous scaphoid fixation. The possible long-term clinical implications of this finding require investigation. CLINICAL RELEVANCE: Our findings indicate that modification of the volar percutaneous approach to scaphoid fixation may be advisable to avoid damage to adjacent structures. We suggest use of a "mini-open" percutaneous procedure. PMID- 26361454 TI - Outcome of Semi-Constrained Total Elbow Arthroplasty in Posttraumatic Conditions with Analysis of Bushing Wear on Stress Radiographs. AB - BACKGROUND: Total elbow arthroplasty for posttraumatic arthritis or nonunion has been associated with a high rate of complications. Bushing wear is a known complication, although the actual incidence is unknown because stress views of the elbow are not routinely performed. We evaluate incidence of bushing wear in total elbow arthroplasty using stress radiographs. METHODS: Eighteen patients underwent total elbow arthroplasty from 1997-2009 for posttraumatic arthritis or distal humerus nonunion using the third generation Coonrad-Moorey design. Eight patients met inclusion criteria and had an average age of 67 years and mean follow-up of 105 months. Radiographs were analyzed for bushing wear and implant loosening on standard and stress radiographs. Clinical outcome measures included the Disabilities of Arm, Shoulder, and Hand (DASH) questionnaire, Mayo Elbow Performance Score (MEPS), overall patient satisfaction, range of motion, and complications. RESULTS: Rate of bushing wear was high, and stress views were five times more sensitive in detecting bushing wear (63%) compared to non-stress views (12%). Seventy-five percent of patients had a good or excellent MEPS. Range of motion slightly improved from pre- to post-operatively. Minor complications were common, but there were no revisions and no cases with radiographic loosening. There was no correlation between bushing wear and the DASH or MEPS. CONCLUSION: Incidence of bushing wear in total elbow arthroplasty is high, and under diagnosed without stress views. Although minor complications are common, frequent loosening and revision do not occur as previously reported for other implants. Despite bushing wear, mid-term functional outcomes are good. LEVEL OF EVIDENCE: Therapeutic IV. PMID- 26361455 TI - Minimally Invasive Versus Open Lumbar Fusion: A Comparison of Blood Loss, Surgical Complications, and Hospital Course. AB - BACKGROUND: Perioperative blood loss is a frequent concern in spine surgery and often necessitates the use of allogeneic transfusion. Minimally invasive technique (MIS) is an option that minimizes surgical trauma and therefore intra operative bleeding. The purpose of this study is to evaluate the blood loss, surgical complications, and duration of inpatient hospitalization in patients undergoing open posterolateral lumbar fusion (PLF), open posterior lumbar interbody fusion (PLIF) with PLF, or MIS transforaminal lumbar interbody fusion (MIS TLIF). METHODS: Operative reports and perioperative data of patients undergoing single-level, primary open PLF (n=41), open PLIF/PLF (n=42), and MIS TLIF (n=71) were retrospectively evaluated. Patient demographics, operative blood loss, use of transfusion products, complications, and length of stay were tabulated. Patient data was controlled for age, BMI, and gender for statistical analysis. RESULTS: Patients undergoing open PLF and open PLIF/PLF respectively experienced a significantly higher blood loss (p<0.001), higher volume of blood transfusion (p<0.001), higher volume of cell saver transfusion (p<0.001), and more surgical complications (dural injury, wound infections, screw malposition) (p=0.02) than those undergoing MIS TLIF. There was no statistically significant difference in duration of hospital stay (p=0.11). CONCLUSIONS: MIS TLIF provides interbody fusion with less intraoperative blood loss and subsequently a lower transfusion rate compared to open techniques, but this did not influence length of hospital stay. MIS TLIF is at least as safe as open techniques with respect to dural tear, wound infection, and screw placement. LEVEL OF EVIDENCE: Level III, Therapeutic. PMID- 26361456 TI - Pediatric Spine Trauma in the United States--Analysis of the HCUP Kid'S Inpatient Database (KID) 1997-2009. AB - BACKGROUND: Few references are available describing the epidemiology of pediatric spine injuries. The purpose of this study is to examine the prevalence, risk factors and trends during the period from 1997 to 2009 of pediatric spine injuries in the United States using a large national database. METHODS: Data was obtained from the Kid's Inpatient Database (KID) developed by the Healthcare Cost and Utilization Project (HCUP), for the years 1997-2009. This data includes >3 million discharges from 44 states and 4121 hospitals on children younger than 20 years. Weighted variables are provided which allow for the calculation of national prevalence rates. The Nationwide Emergency Department Sample (NEDS), HCUP. net, and National Highway Traffic Safety Administration (NHTSA) data were used for verification and comparison. RESULTS: A prevalence of 107.96 pmp (per million population) spine injuries in children and adolescents was found in 2009, which is increased from the 77.07 pmp observed in 1997. The group 15 to 19 years old had the highest prevalence of all age groups in (345.44 pmp). Neurological injury was present in 14.6% of the cases, for a prevalence of 15.82 pmp. The majority (86.7%) of these injuries occurred in children >15 years. Motor vehicle collisions accounted for 52.9% of all spine injuries, particularly in children >15 years. Between 1997 and 2009 the hospital length of stay decreased, but hospital charges demonstrated a significant increase. CONCLUSIONS: Pediatric Spine Injuries continue to be a relevant problem, with rates exceeding those of other industrialized nations. Teenagers >15 years of age were at greatest risk, and motor vehicle collisions accounted for the most common mechanism. An increase in prevalence was observed between 1997 and 2009, and this was matched by a similar increase in hospital charges. LEVEL OF EVIDENCE: III. PMID- 26361457 TI - Assessment of SiCaP-30 in a Rabbit Posterolateral Fusion Model with Concurrent Chemotherapy. AB - Chemotherapy derivatives of the rabbit posterolateral fusion model are considered a challenging environment in which to test bone graft materials. The purpose of this study was to determine the performance characteristics of SiCaP-30 as a bone graft substitute relative to autograft (iliac crest bone graft [ICBG]), Actifuse ABX and beta-Tricalcium Phosphate-Bioactive Glass-Type I Collagen (betaTCP-BG) in a rabbit posterolateral spine fusion model with concurrent chemotherapy treatment This was a randomized, controlled study in a laboratory setting with blinded assessment of fusion by manual palpation and flexibility testing. Sixty rabbits were entered into the study with 45 used for analysis. Chemotherapeutic agents, doxorubicin and cis-platin (2.5 mg/kg), were administered one week prior to surgery, and one, two and three weeks post surgery. Bilateral posterolateral lumbar intertransverse process fusions were performed at L5-L6. The lateral two thirds of the transverse processes were decorticated and covered with 3cc/side of one of the following graft materials: autologous ICBG, Actifuse ABX (ApaTech Ltd, UK), Vitoss BA (Orthovita, USA) or SiCaP-30 (ApaTech Ltd., UK). Animals were euthanized 12 weeks post surgery. The ICBG group had a 45% (5/11) manual palpation fusion rate and correlated with motion analysis fusion results of 36% (4/11). The Actifuse ABX group had a 33% (4/12) manual palpation fusion rate and a motion analysis fusion rate of 25% (3/12). No motion segments in the Vitoss BA group (0/11) showed any signs of fusion. The SiCaP-30 group demonstrated a statistically higher manual palpation and motion analysis fusion rate of 82% (9/11; p<0.05) and produced superior bone formation compared with Actifuse ABX and betaTCP-BG. PMID- 26361458 TI - Risk Factors for Nonroutine Discharge in Patients Undergoing Spinal Fusion for Intervertebral Disc Disorders. AB - BACKGROUND: Although outcomes following spinal fusion for intervertebral disc disorders have been studied, factors influencing discharge disposition and health care resource utilization have not been determined. This study sought to clarify perioperative risk factors for non-routine discharge and prolonged hospital stay in patients undergoing fusion for intervertebral disc disorders. METHODS: The National Hospital Discharge Survey was queried to identify all patients discharged from U.S. hospitals following spinal fusion for intervertebral disc disorders between 1990 and 2007. A cohort representative of 1,943,707 patients was identified and separated into those who were discharged home and those who were discharged to rehabilitation facilities. Multivariable logistic regression analysis was used to identify independent predictors of non-routine discharge to another inpatient facility and prolonged hospital stay. RESULTS: The strongest risk factors for non-routine discharge were age>65 years, congestive heart failure, atrial fibrillation, any general in-hospital complication, diabetes mellitus, osteoporosis, hypertension and any surgery-related complication. Patients younger than 50 years and males had the lowest rate of non-routine discharge. The strongest risk factors for prolonged hospital stay were any surgery-related complication, congestive heart failure, any general in-hospital complication, atrial fibrillation, age > 65 years, osteoporosis and diabetes mellitus. Patients 36-50 years of age had the lowest risk of increased length of hospital stay. CONCLUSIONS: Knowledge of these risk factors may aid in better resource allocation and improved strategies for managing patients with spondylosis in order to decrease healthcare costs. LEVEL OF EVIDENCE: 3. PMID- 26361459 TI - Prenatal Ultrasound Diagnosis of Congenital Talipes Equinovarus in Bogota (Colombia) Between 2003 and 2012. AB - INTRODUCTION: Congenital Talipes Equinovarus (CTEV) or clubfoot is one of the most common congenital abnormalities(1,2). Early diagnosis by means of ultrasonography allows an opportune intervention and improves the deformity's correction prognosis. GOAL: To describe patients diagnosed with CTEV by means of prenatal sonographies between 2003 and 2012 in Bogota (Colombia) at both the Institute de Ortopedia Infantil Roosevelt (IOIR) and one of the authors' private office. METHODS: A descriptive, retrospective study on the focus population was made. The equality of the data of the quantitative variables in distance measure was analysed by the Kolmogorov-Smirnov test. For the variables "prenatal diagnoses" and "days from the start of the treatment" the Mann-Whitney U test was used. Finally, an analysis was made by means of the SPSS Statistics software package, version 18.0. RESULTS: 178 patients met the selection criteria. 34.3% of the patients had a prenatal diagnosis by ultrasonography (n=61). Regarding the number of prenatal ultrasounds performed, there were statistically significant differences between the patients with a CTEV prenatal diagnoses and those whose diagnoses came after birth, being higher in the first group (p<0.001). The number of days before the treatment started once the pre or postnatal diagnosis was done was also a subject of study. Significant differences were found in the treatment start between patients with a prenatal diagnosis (mean of 9.9 days) and those diagnosed after birth (mean of 30 days) (p<0.001). CONCLUSIONS: prenatal diagnosis by foetal ultrasonography contributes to an early detection of musculoskeletal abnormalities such as CTEV and promotes an early intervention of the patient. PMID- 26361460 TI - Photovoice and Clubfoot: Using a Participatory Research Method to Study Caregiver Adherence to the Ponseti Method in Peru. AB - The Ponseti Method of casting and bracing is the gold-standard treatment for congenital clubfoot in young children. Despite its many advantages, outcomes depend heavily on caregiver adherence to the treatment protocol. Our study explored the experience caregivers had with the Ponseti method using a photography-based participatory research method known as Photovoice. Five adult caregivers were recruited from families pursuing clubfoot treatment at the Children's Hospital in Lima, Peru, during June, 2013. Each was provided a digital camera and training and agreed to photograph their experiences caring for a child undergoing Ponseti Method clubfoot treatment. Participants held four to five weekly one-on-one meetings with the researcher to discuss their photos. They also attended a group meeting at the end of the study to view and discuss photos of other participants. Using photos collected at this meeting, participants identified themes that summarized their experiences with treatment and discussed ways to improve delivery of care in order to support caregiver adherence to treatment. These results were presented to clinicians in Lima who use the Ponseti Method. The Photovoice method allowed researchers and participants to study the experience caregivers have with the Ponseti Method, and results can be used to inform the design of patient-based care models. PMID- 26361461 TI - The Heel Pad in Congenital Idiopathic Clubfoot: Implications of Empty Heel for Clinical Severity Assessment. AB - BACKGROUND: Clubfoot has been evaluated in many ways, including the most common classifications of clubfoot, described by Caterrall and Piraniis based on six clinical signs. The purpose of this study was to gain better understanding of the heel pad in relation to the term "empty heel", and to propose modification of clubfoot severity scoring system based on "empty heel". METHODS: A combination of prospective study of 79 clubfoot patients treated with Ponseti method and literature review of heel pad anatomy and biomechanics. The setting was a university teaching hospital. The ethical research committee approved study protocol and informed consent of patients' parent obtained. The selection criteria included patients' diagnosed congenital idiopathic clubfoot, age < 2 years, no history of previous treatment and tenotomy indicated. An evaluation of patient was assessed by orthopaedic surgeons trained on Ponseti method and has above 5 years experience. Data analysis performed on the age, sex, Pirani scores at onset of treatment, tenotomy, and 6 month after initial full correction. RESULTS: One hundred and thirty-two clubfeet in 79 patients (56 males, 23 females) completed Ponseti protocol. The median age at presentation was 5.2 months (range 0.1-23.7 months). The mean right foot abduction after correction 57.30 (S.D. 9.20), and for the left foot, was 56.30 (S.D. 9.40). The mean right foot dorsiflexion was -13.70 (S.D. 18.40) before correction while after correction, it was 20.00 (S.D. 4.50) and for the left, the mean was -8.50 (S.D. 9.60) before correction and 21.00 (S.D. 4.30) after correction. Eighteen (22.8%) patients (10 bilateral, 9 unilateral) had clubfeet with empty heel score above zero point at initial full correction (p<0.001). Clinic anatomy shows the heel pad is a solid complex structure existing in normal, moderate and severe atrophied form. Heel pad is attached tightly to calcaneus without a cavity for the calcaneus to drop. CONCLUSIONS: Heel pad probably could replace "empty heel" in modify Pirani scoring system. Clinical indication for repeat tenotomy should be based on equinus, not on the feeling of an empty heel, and families can be advised that the heel pad has a tendency to remodel over time to a normal shape. LEVEL OF EVIDENCE: Level II. CLINICAL RELEVANCE: Empty heel feeling at initial full correction of congenital idiopathic clubfoot based on Ponseti protocol is not indication for repeat tenotomy. PMID- 26361462 TI - Outcomes of a Simple Treatment for Complex Regional Pain Syndrome Type I in Children. AB - BACKGROUND: Chronic Regional Pain Syndrome type I (CRPSI) in children is a disorder of unknown etiology. No standard diagnostic criteria or treatment exists. Published treatment protocols are often time and resource intensive. Nonetheless, CRPSI is not rare and can be disabling. This reports the results of a simple and inexpensive treatment protocol involving no medicines, nerve blockades, physical therapy resources or referrals to pain specialists. The patient is instructed in a self-administered massage and mobilization program. The diagnosis required allodynia (pain on light touch of the skin) and signs or the history of signs of autonomic dysfunction. METHODS: A chart review of patient coded for "reflex sympathetic dystrophy" or 'autonomic dysfunction" was performed yielding a cohort of eighty-three patients treated by a common protocol. Most patients were identified in the last 15 years. Most patients with this CRPSI were doubtless coded simply as "foot pain" or "knee pain", etc and were not identified in this search. Charts were reviewed for patient demographics and outcomes. A subset of patients filled out the Pediatric Outcomes Data Collection Instrument (PODCI) giving a validated pre-treatment disability measure. RESULTS: The cohort characteristics were similar to prior reports with respect to age, gender, location, and history of trauma. Of the 26 patients who completed the PODCI before treatment the Pain/Comfort Core Scale score mean was 20.81(0-63). The Global Functioning Scale score mean was 52.11(27-83.5). Eighty-nine percent of 51 patients who attended clinic until their outcome was definite had no or minimal residual pain. Treatment averaged 2.2 visits per patient, typically over a six week period. CONCLUSIONS: A simple, inexpensive protocol can be effective in treating CRPSI in children. The protocol is risk free, inexpensive to families and conservative of physician and physical therapy resources. LEVEL OF EVIDENCE: Therapeutic Level IV. PMID- 26361463 TI - The Variability in Surgical Margin Reporting in Limb Salvage Surgery for Sarcoma. AB - BACKGROUND: Surgical margins are a standard reported measurement in tumor surgery that has implications for functional outcome, local control, and overall survival. There is no single accepted classification, and it is unclear what form or margin reporting predominates in the sarcoma literature. METHODS: We performed a PubMed literature search to identify articles that reported surgical margins and oncologic outcomes in limb salvage surgery for sarcoma from 1980 to 2013. We recorded the margin classification, specialty of the journal, specialty of the author, and location of the authors' institution. RESULTS: We found that 159/448 (35%) of articles included in the study did not report surgical margins. Of the 289 papers that did include data on margins, 160 (55%) of articles used Enneking's classification. There has been an increase over time in the proportion of articles reporting surgical margins by the residual tumor (R) classification and the proportion of articles reporting margins dichotomously as "positive" or "negative." CONCLUSIONS: We did not find a common method for reporting margins in the limb salvage sarcoma literature. Of most concern was over 1/3 of clinical reports of oncologic outcomes did not include margin status, which substantially compromises any conclusions that readers may infer about treatment success, local recurrence, or survival. We believe there should be renewed efforts to encourage use of a common surgical margin reporting system that is simple, reproducible, and prognostic. PMID- 26361464 TI - Health Literacy in Patients Seeking Orthopaedic Care: Results of the Literacy in Musculoskeletal Problems (LIMP) Project. AB - BACKGROUND: Health literacy is the most important predictor of an individual's health status, with more frequent hospitalizations, worse control of chronic conditions, and suboptimal treatment outcomes associated with limited literacy. Despite this, little is known about musculoskeletal health literacy. As such, this study utilized a musculoskeletal specific literacy survey (the LiMP questionnaire) to evaluate the level of comprehension in patients presenting to the emergency department with musculoskeletal complaints, with an emphasis on their understanding of anatomy, terminology, diagnosis and treatment of musculoskeletal conditions. The relationship between musculoskeletal specific and general health literacy was also assessed, in addition to the risk factors for limited musculoskeletal comprehension. METHODS: In this cross-sectional study, each of the 248 participants completed a demographic survey, the LiMP questionnaire, and the Newest Vital Sign (NVS), a general health literacy assessment tool. A x(2) analysis was used to compare results from the LiMP questionnaire and NVS, and to evaluate the relationship between musculoskeletal health literacy and demographic parameters. RESULTS: The mean LiMP score was 4.68 +/- 1.78 out of a possible nine points. Questions regarding musculoskeletal conditions were answered correctly by 47.4% of respondents. Questions regarding diagnosis and treatment were answered correctly by 31.2% of respondents. Questions regarding anatomy and terminology were answered correctly by 65.3% of respondents. Limited musculoskeletal literacy, defined as LiMP questionnaire scores of <6, was observed in 69% of subjects. Inadequate general health literacy, defined as NVS scores <4, was observed in 48% of subjects. This difference was statistically significant (p<0.001). Those who identified themselves as Caucasian and having an education level of >= college were significantly more likely to have adequate musculoskeletal literacy (p=0.001, p<0.001, respectively). CONCLUSIONS: The prevalence of limited musculoskeletal literacy is greater than that of limited general health literacy, with minorities and those with lower education levels most at risk. These findings are consistent with other disease and specialty specific literacy studies. Although such insight will assist providers in accurately targeting education and outreach campaigns, it remains imperative that additional research be performed to determine if limited literacy correlates with increased complications and worse outcomes in those with musculoskeletal conditions. LEVEL OF EVIDENCE: Level IV. The authors have no relevant financial disclosures or conflicts of interest with regard to this manuscript. No funding was received. PMID- 26361465 TI - Evaluation of Different Experience Levels of Orthopaedic Residents Effect on Polymethylmethacrylate (PMMA) Bone Cement Mechanical Properties. AB - BACKGROUND: PMMA bone cement is a brittle material and the creation of defects that increase porosity during mixing or injecting is a significant factor in reducing its mechanical properties. The goal during residency training is to learn how to avoid creating increased porosity during mixing and injecting the material. The aim of this study was to evaluate and compare tensile and compression strength for PMMA cement mixed by intern orthopaedic residents (PGY 1) and senior orthopaedic residents (PGY-5). The hypothesis was that the mechanical properties of PMMA cement mixed by PGY-5 would be significantly better than PMMA cement mixed by PGY-1 residents. METHODS: Four PGY-1 and four PGY-5 orthopaedic residents each prepared eight tensile specimens. The bone cement used was SimplexTM P bone cement (Stryker Howmedica Osteonics, Mahwah, NJ) under vacuum mixing in a cement-delivery system. Tensile testing of the specimens was performed in an MTS Bionix servohydraulic materials testing system with loading rate of 2.54 mm/min at room temperature. The mean and standard deviation of the ultimate tensile strength (UTS) for each orthopaedic resident group was calculated. The compression specimens were cylinders formed with a central core to mimic a prosthetic implant. Ten samples from each orthopaedic resident were tested using the same MTS system under identical conditions at room temperature. The specimens were loaded from -50 N to complete structural failure at the rate of 20 mm/min. The ultimate compressive strength (UCS) was then determined and the mean and standard deviation calculated for each group. RESULTS: The average UTS of the bone cement for the PGY-1 and PGY-5 residents was 37.5 +/- 4.5 MPa and 39.2 +/- 5.0 MPa, respectively, and there was no statistically significant difference between the two groups. For the tensile elastic modulus of the bone cement, the results for the PGY-1 and PGY-5 residents were 2.40 +/- 0.09 GPa and 2.44 +/- 0.08 GPa, respectively, and again there was no statistically significant difference. For the compression elastic modulus of the bone cement, the results for the PGY-1 and PGY-5 residents were 1.19 +/- 0.13 GPa and 1.21 +/- 0.18 GPa, respectively, with no statistically significant difference. However, the UCS of the bone cement for the PGY-1 and PGY-5 residents was 87.4 +/- 5.8 MPa and 91.1 +/- 4.5 MPa, respectively, and there was a statistically significant difference between the groups. DISCUSSION: The PMMA specimens prepared by both the PGY-1 and PGY-5 resident groups had similar characteristics during tensile and compression testing, and were similar to known standards. Although mixing and applying bone cement is an important skill for joint replacement surgery, our results indicate that no special training appears to be necessary for orthopaedic residents. Rather, a basic training video demonstrating manufacturer standard procedure is all that is necessary. CLINICAL RELEVANCE: The results of this study indicate the importance of experience in bone cement mixing and injecting on cement mechanical properties, but indicate that no special training appears to be necessary for orthopaedic residents. PMID- 26361466 TI - Is There a Partial Consensus Ordering Between Rankings? AB - We propose an innovative approach to the problem recently posed by Hall and Schimek (2012): determining at what point the agreement between two rankings of a long list of items degenerates into noise. We modify the method of estimation in Fligner and Verducci's (1988) multistage model for rankings, from maximum likelihood of conditional agreement over a sample of rankings to a locally smooth estimator of agreement. Through simulations we show that this innovation performs very well under several conditions. Some ramifications are discussed as planned extensions. PMID- 26361467 TI - Magnetic Resonance Elastography. AB - Often compared to the practice of manual palpation, magnetic resonance elastography is an emerging technology for quantitatively assessing the mechanical properties of tissue as a basis for characterizing disease. The potential of MRE as a diagnostic tool is rooted in the fact that normal and diseased tissues often differ significantly in terms of their intrinsic mechanical properties. MRE uses magnetic resonance imaging (MRI) in conjunction with the application of mechanical shear waves to probe tissue mechanics. This process can be broken down into three essential steps: inducing shear waves in the tissue,imaging the propagating shear waves with MRI, andanalyzing the wave data to generate quantitative images of tissue stiffness MRE has emerged as a safe, reliable and noninvasive method for staging hepatic liver fibrosis, and is now used in some locations as an alternative to biopsy. MRE is also being used in the ongoing investigations of numerous other organs and tissues, including, for example, the spleen, kidney, pancreas, brain, heart, breast, skeletal muscle, prostate, vasculature, lung, spinal cord, eye, bone, and cartilage. In the article that follows, some fundamental techniques and applications of MRE are summarized. PMID- 26361468 TI - Genetic Variability and Geographical Distribution of Mycotoxigenic Fusarium verticillioides Strains Isolated from Maize Fields in Texas. AB - Maize is the dominant cereal crop produced in the US. One of the main fungal pathogens of maize is Fusarium verticillioides, the causative agent of ear and stalk rots. Significantly, the fungus produces a group of mycotoxins - fumonisins - on infested kernels, which have been linked to various illnesses in humans and animals. Nonetheless, durable resistance against F. verticillioides in maize is not currently available. In Texas, over 2.1 million acres of maize are vulnerable to fumonisin contamination, but understanding of the distribution of toxigenic F. verticillioides in maize-producing areas is currently lacking. Our goal was to investigate the genetic variability of F. verticillioides in Texas with an emphasis on fumonisin trait and geographical distribution. A total of 164 F. verticillioides cultures were isolated from 65 maize-producing counties. DNA from each isolate was extracted and analyzed by PCR for the presence of FUM1- a key fumonisin biosynthesis gene - and mating type genes. Results showed that all isolates are in fact F. verticillioides capable of producing fumonisins with a 1:1 mating-type gene ratio in the population. To further study the genetic diversity of the population, isolates were analyzed using RAPD fingerprinting. Polymorphic markers were identified and the analysis showed no clear correlation between the RAPD profile of the isolates and their corresponding geographical origin. Our data suggest the toxigenic F. verticillioides population in Texas is widely distributed wherever maize is grown. We also hypothesize that the population is fluid, with active movement and genetic recombination occurring in the field. PMID- 26361469 TI - Development of a Species-specific PCR Assay for Three Xanthomonas Species, Causing Bulb and Flower Diseases, Based on Their Genome Sequences. AB - In this study, we developed a species-specific PCR assay for rapid and accurate detection of three Xanthomonas species, X. axonopodis pv. poinsettiicola (XAP), X. hyacinthi (XH) and X. campestris pv. zantedeschiae (XCZ), based on their draft genome sequences. XAP, XH and XCZ genomes consist of single chromosomes that contain 5,221, 4,395 and 7,986 protein coding genes, respectively. Species specific primers were designed from variable regions of the draft genome sequence data and assessed by a PCR-based detection method. These primers were also tested for specificity against 17 allied Xanthomonas species as well as against the host DNA and the microbial community of the host surface. Three primer sets were found to be very specific and no amplification product was obtained with the host DNA and the microbial community of the host surface. In addition, a detection limit of 1 pg/MUl per PCR reaction was detected when these primer sets were used to amplify corresponding bacterial DNAs. Therefore, these primer sets and the developed species-specific PCR assay represent a valuable, sensitive, and rapid diagnostic tool that can be used to detect three specific pathogens at early stages of infection and may help control diseases. PMID- 26361470 TI - Development of a Rapid Detection Method for Potato virus X by Reverse Transcription Loop-Mediated Isothermal Amplification. AB - The primary step for efficient control of viral diseases is the development of simple, rapid, and sensitive virus detection. Reverse transcription loop-mediated isothermal amplification (RT-LAMP) has been used to detect viral RNA molecules because of its simplicity and high sensitivity for a number of viruses. RT-LAMP for the detection of Potato virus X (PVX) was developed and compared with conventional reverse transcription polymerase chain reaction (RT-PCR) to demonstrate its advantages over RT-PCR. RT-LAMP reactions were conducted with or without a set of loop primers since one out of six primers showed PVX specificity. Based on real-time monitoring, RT-LAMP detected PVX around 30 min, compared to 120 min for RT-PCR. By adding a fluorescent reagent during the reaction, the extra step of visualization by gel electrophoresis was not necessary. RT-LAMP was conducted using simple inexpensive instruments and a regular incubator to evaluate whether RNA could be amplified at a constant temperature instead of using an expensive thermal cycler. This study shows the potential of RT-LAMP for the diagnosis of viral diseases and PVX epidemiology because of its simplicity and rapidness compared to RT-PCR. PMID- 26361472 TI - Reaction of Five Non-cereal Grasses to Five Races and Two Host Selective Toxins of Pyrenophora tritici-repentis. AB - Alternative hosts increase the difficulty of disease management in crops because these alternate hosts provide additional sources of primary inoculum or refuges for diversity in the pathogen gene pool. Agropyron cristatum (crested wheatgrass), Bromus inermis (smooth bromegrass), Pascopyrum smithii (western wheatgrass), Stipa viridula (green needlegrass), and Thinopyrum intermedium (intermediate wheatgrass), commonly identified in range, prairie, verge, and soil reclamation habitats, serve as additional hosts for Pyrenophora tritici-repentis, the cause of tan spot in wheat (Triticum aestivum L.). A. cristatum (five lines), B. inermis (seven lines), P. smithii (four lines), S. viridula (two lines), and T. intermedium (six lines) were tested for their reactions to 30 representative P. tritici-repentis isolates from races 1-5. Plants were grown until the two three-leaf stage in a greenhouse, inoculated individually with the 30 isolates, held at high humidity for 24 h, and rated after 7 days. All lines developed lesion types 1-2 (resistant) based on a 1-5 rating scale. Also, leaves from an additional plant set were infiltrated with two host selective toxins, Ptr ToxA as a pure preparation and Ptr ToxB as a dilute crude culture filtrate. All lines were insensitive to the toxins. Results indicate that these grass hosts have a limited or nonsignificant role in tan spot epidemiology on wheat in the northern Great Plains. Additionally, the resistant reactions demonstrated by the grass species in this research indicate the presence of resistance genes that can be valuable to wheat breeding programs for improving wheat resistance to P. tritici repentis. PMID- 26361471 TI - Relationships between Genetic Diversity and Fusarium Toxin Profiles of Winter Wheat Cultivars. AB - Fusarium head blight is one of the most important and most common diseases of winter wheat. In order to better understanding this disease and to assess the correlations between different factors, 30 cultivars of this cereal were evaluated in a two-year period. Fusarium head blight resistance was evaluated and the concentration of trichothecene mycotoxins was analysed. Grain samples originated from plants inoculated with Fusarium culmorum and naturally infected with Fusarium species. The genetic distance between the tested cultivars was determined and data were analysed using multivariate data analysis methods. Genetic dissimilarity of wheat cultivars ranged between 0.06 and 0.78. They were grouped into three distinct groups after cluster analysis of genetic distance. Wheat cultivars differed in resistance to spike and kernel infection and in resistance to spread of Fusarium within a spike (type II). Only B trichothecenes (deoxynivalenol, 3-acetyldeoxynivalenol and nivalenol) produced by F. culmorum in grain samples from inoculated plots were present. In control samples trichothecenes of groups A (H-2 toxin, T-2 toxin, T-2 tetraol, T-2 triol, scirpentriol, diacetoxyscirpenol) and B were detected. On the basis of Fusarium head blight assessment and analysis of trichothecene concentration in the grain relationships between morphological characters, Fusarium head blight resistance and mycotoxins in grain of wheat cultivars were examined. The results were used to create of matrices of distance between cultivars - for trichothecene concentration in inoculated and naturally infected grain as well as for FHB resistance Correlations between genetic distance versus resistance/mycotoxin profiles were calculated using the Mantel test. A highly significant correlation between genetic distance and mycotoxin distance was found for the samples inoculated with Fusarium culmorum. Significant but weak relationships were found between genetic distance matrix and FHB resistance or trichothecene concentration in naturally infected grain matrices. PMID- 26361473 TI - Expression of Rice Chitinase Gene in Genetically Engineered Tomato Confers Enhanced Resistance to Fusarium Wilt and Early Blight. AB - This is the first study reporting the evaluation of transgenic lines of tomato harboring rice chitinase (RCG3) gene for resistance to two important fungal pathogens Fusarium oxysporum f. sp. lycopersici (Fol) causing fusarium wilt and Alternaria solani causing early blight (EB). In this study, three transgenic lines TL1, TL2 and TL3 of tomato Solanum lycopersicum Mill. cv. Riogrande genetically engineered with rice chitinase (RCG 3) gene and their R1 progeny was tested for resistance to Fol by root dip method and A. solani by detached leaf assay. All the R0 transgenic lines were highly resistant to these fungal pathogens compared to non-transgenic control plants. The pattern of segregation of three independent transformant for Fol and A. solani was also studied. Mendelian segregation was observed in transgenic lines 2 and 3 while it was not observed in transgenic line 1. It was concluded that introduction of chitinase gene in susceptible cultivar of tomato not only enhanced the resistance but was stably inherited in transgenic lines 2 and 3. PMID- 26361474 TI - Effect of Aerated Compost Tea on the Growth Promotion of Lettuce, Soybean, and Sweet Corn in Organic Cultivation. AB - This study investigated the chemical characteristics and microbial population during incubation of four kinds of aerated compost teas based on oriental medicinal herbs compost, vermicompost, rice straw compost, and mixtures of three composts (MOVR). It aimed to determine the effects of the aerated compost tea (ACT) based on MOVR on the growth promotion of red leaf lettuce, soybean and sweet corn. Findings showed that the pH level and EC of the compost tea slightly increased based on the incubation time except for rice straw compost tea. All compost teas except for oriental medicinal herbs and rice straw compost tea contained more NO(-) 3-N than NH(+) 4-N. Plate counts of bacteria and fungi were significantly higher than the initial compost in ACT. Microbial communities of all ACT were predominantly bacteria. The dominant bacterial genera were analyzed as Bacillus (63.0%), Ochrobactrum (13.0%), Spingomonas (6.0%) and uncultured bacterium (4.0%) by 16S rDNA analysis. The effect of four concentrations, 0.1%, 0.2%, 0.4% and 0.8% MOVR on the growth of red leaf lettuce, soybean and sweet corn was also studied in the greenhouse. The red leaf lettuce with 0.4% MOVR had the most effective concentration on growth parameters in foliage part. However, 0.8% MOVR significantly promoted the growth of root and shoot of both soybean and sweet corn. The soybean treated with higher MOVR concentration was more effective in increasing the root nodule formation by 7.25 times than in the lower MOVR concentrations Results indicated that ACT could be used as liquid nutrient fertilizer with active microorganisms for culture of variable crops under organic farming condition. PMID- 26361475 TI - Application of Volatile Antifungal Plant Essential Oils for Controlling Pepper Fruit Anthracnose by Colletotrichum gloeosporioides. AB - Anthracnose caused by Colletotrichum gloeosporioides has been destructive during pepper fruit production in outdoor fields in Korea. In vitro antifungal activities of 15 different plant essential oils or its components were evaluated during conidial germination and mycelial growth of C. gloeosporioides. In vitro conidial germination was most drastically inhibited by vapour treatments with carvacrol, cinnamon oil, trans-cinnamaldehyde, citral, p-cymene and linalool. Inhibition of the mycelial growth by indirect vapour treatment with essential oils was also demonstrated compared with untreated control. Carvacrol, cinnamon oil, trans-cinnamaldehyde, citral and eugenol were among the most inhibitory plant essential oils by the indirect antifungal efficacies. Plant protection efficacies of the plant essential oils were demonstrated by reduced lesion diameter on the C. gloeosporioides-inoculated immature green pepper fruits compared to the inoculated control fruits without any plant essential oil treatment. In planta test showed that all plant essential oils tested in this study demonstrated plant protection efficacies against pepper fruit anthracnose with similar levels. Thus, application of different plant essential oils can be used for eco-friendly disease management of anthracnose during pepper fruit production. PMID- 26361476 TI - Antagonistic Potential of Native Trichoderma viride Strain against Potent Tea Fungal Pathogens in North East India. AB - Indigenous strains of Trichoderma species isolated from rhizosphere soils of Tea gardens of Assam, north eastern state of India were assessed for in vitro antagonism against two important tea fungal pathogens namely Pestalotia theae and Fusarium solani. A potent antagonist against both tea pathogenic fungi, designated as SDRLIN1, was selected and identified as Trichoderma viride. The strain also showed substantial antifungal activity against five standard phytopathogenic fungi. Culture filtrate collected from stationary growth phase of the antagonist demonstrated a significantly higher degree of inhibitory activity against all the test fungi, demonstrating the presence of an optimal blend of extracellular antifungal metabolites. Moreover, quantitative enzyme assay of exponential and stationary culture filtrates revealed that the activity of cellulase, beta-1,3-glucanase, pectinase, and amylase was highest in the exponential phase, whereas the activity of proteases and chitinase was noted highest in the stationary phase. Morphological changes such as hyphal swelling and distortion were also observed in the fungal pathogen grown on potato dextrose agar containing stationary phase culture filtrate. Moreover, the antifungal activity of the filtrate was significantly reduced but not entirely after heat or proteinase K treatment, demonstrating substantial role of certain unknown thermostable antifungal compound(s) in the inhibitory activity. PMID- 26361477 TI - Outbreaks of Yuzu Dieback in Goheung Area: Possible Causes Deduced from Weather Extremes. AB - Starting in 2012, severe diebacks usually accompanied by abundant gum exudation have occurred on yuzu trees in Goheung-gun, Jeonnam Province, where severely affected trees were occasionally killed. On-farm surveys were conducted at 30 randomly-selected orchards located at Pungyang-myeon, Goheung-gun, and the resulting disease incidences were 18.5% and 39.6% for dieback and gumming symptoms, respectively. Black spots on branches and leaves also appeared on infected trees showing a typical dieback symptom. Morphological and molecular identifications of the isolated fungal organisms from lesions on the symptomatic leaves and branches revealed that they are identical to Phomopsis citri, known to cause gummosis. In order to find the reason for this sudden epidemic, we investigated the weather conditions that are exclusively distinct from previous years, hypothesizing that certain weather extremes might have caused the severe induction of pre-existing disease for yuzu. There were two extreme temperature drops beyond the yuzu's cold hardiness limit right after an abnormally-warm temperature-rise during the winter of 2011-12, which could cause severe frost damage resulting in mechanical injuries and physiological weakness to the affected trees. Furthermore, there was an increased frequency of strong wind events, seven times in 2012 compared to only a few times in the previous years, that could also lead to extensive injuries on branches. In conclusion, we estimated that the possible damages by severe frost and frequent strong wind events during 2012 could cause the yuzu trees to be vulnerable to subsequent fungal infection by providing physical entries and increasing plant susceptibility to infections. PMID- 26361478 TI - Ultrastructure of the Rust Fungus Puccinia miscanthi in the Teliospore Stage Interacting with the Biofuel Plant Miscanthus sinensis. AB - Interaction of the the rust fungus Puccinia miscanthi with the biofuel plant Miscanthus sinensis during the teliospore phase was investigated by light and electron microscopy. P. miscanthi telia were oval-shaped and present on both the adaxial and abaxial leaf surfaces. Teliospores were brown, one-septate (two celled), and had pedicels attached to one end. Transmission electron microscopy revealed numerous electron-translucent lipid globules in the cytoplasm of teliospores. Extensive cell wall dissolution around hyphae was not observed in the host tissues beneath the telia. Hyphae were found between mesophyll cells in the leaf tissues as well as in host cells. Intracellular hyphae, possibly haustoria, possessed electron-dense fungal cell walls encased by an electron transparent fibrillar extrahaustorial sheath that had an electron-dense extrahaustorial membrane. The infected host cells appeared to maintain their membrane-bound structures such as nuclei and chloroplasts. These results suggest that the rust fungus maintains its biotrophic phase with most mesophyll cells of M. sinensis. Such a nutritional mode would permit the rust fungus to obtain food reserves for transient growth in the course of host alteration. PMID- 26361479 TI - Fitness is Recovered with the Decline of Dimethachlon Resistance in Laboratory induced Mutants of Sclerotinia sclerotiorum after Long-term Cold Storage. AB - After four years of cold storage, dimethachlon resistance of two laboratory induced resistant Sclerotinia sclerotiorum isolates SCG7 and LA50 declined by 99.5% and 98.9%, respectively, and cross resistance to iprodione and procymidone also declined dramatically. Along with the decline of fungicide resistance, osmotic sensitivity to sodium chloride and glucose decreased tremendously; mycelial growth rate, sclerotia number and weight per potato dextrose agar (PDA) plate increased on average by 118.6%, 85. 5% and 64.5%, respectively; and virulence to detached leaves of oilseed rape increased by 72.7% on average. Significant negative correlations were detected between dimethachlon resistance levels and mycelial growth rate on PDA (r = -0.980, P = 0.021), and between resistance levels and lesion diameters on detached leaves of oilseed rape plants (r = -0.997, P = 0.002). These results have profound implications for assessing the potential risk for resistance development to dicarboximide fungicides in S. sclerotiorum. PMID- 26361480 TI - Plant Growth-Promoting Rhizobacteria Stimulate Vegetative Growth and Asexual Reproduction of Kalanchoe daigremontiana. AB - Certain bacterial species associate with plant roots in soil. The plant growth promoting rhizobacteria (PGPR) stimulate plant growth and yield in greenhouse and field. Here, we examined whether application of known bacilli PGPR strains stimulated growth and asexual reproduction in the succulent plant Kalanchoe daigremontiana. Four PGPR strains B. amyloliquefaciens IN937a, B. cereus BS107, B. pumilus INR7, and B. subtilis GB03 were applied to young plantlets by soil drenching, and plant growth and development was monitored for three months. Aerial growth was significantly stimulated in PGPR-inoculated plants, which was observed as increases in plant height, shoot weight, and stem width. The stimulated growth influenced plant development by increasing the total number of leaves per plant. Treatment with bacilli also increased the total root biomass compared with that of control plants, and led to a 2-fold increase in asexual reproduction and plantlet formation on the leaf. Collectively, our results firstly demonstrate that Bacillus spp. promote vegetative development of K. daigremontiana, and the enhanced growth stimulates asexual reproduction and plantlet formation. PMID- 26361481 TI - Antifungal Activity of a Synthetic Cationic Peptide against the Plant Pathogens Colletotrichum graminicola and Three Fusarium Species. AB - A small cationic peptide (JH8944) was tested for activity against a number of pathogens of agricultural crops. JH8944 inhibited conidium growth in most of the tested plant pathogens with a dose of 50 MUg/ml, although one isolate of Fusarium oxysporum was inhibited at 5 MUg/ml of JH8944. Most conidia of Fusarium graminearum were killed within 6 hours of treatment with 50 MUg/ml of JH8944. Germinating F. graminearum conidia required 238 MUg/ml of JH8944 for 90% growth inhibition. The peptide did not cause any damage to tissues surrounding maize leaf punctures when tested at a higher concentration of 250 MUg/ml even after 3 days. Liposomes consisting of phosphatidylglycerol were susceptible to leakage after treatment with 25 and 50 MUg/ml of JH8944. These experiments suggest this peptide destroys fungal membrane integrity and could be utilized for control of crop fungal pathogens. PMID- 26361482 TI - Get shorty! PMID- 26361483 TI - Should pediatric infectious diseases physicians be proponents of probiotics? PMID- 26361484 TI - A slowly growing flank mass. PMID- 26361485 TI - The role of pediatricians as key stakeholders in influencing immunization policy decisions for the introduction of meningitis B vaccine in Canada: The Ontario perspective. AB - As key stakeholders in immunization policy decisions, the Pediatricians of Ontario held an accredited conference on January 18, 2014, to discuss prevention of invasive meningococcal disease. Five key recommendations were put forth regarding immunization strategies to protect children from meningococcal serogroup B disease. The recently approved four-component meningococcal B (4CMenB) vaccine should be recommended and funded as part of Ontario's routine immunization schedule and should also be mandated for school attendance. Public funding for 4CMenB immunization is justified based on current MenB epidemiology, vaccine coverage, cost effectiveness and acceptability, as well as legal, political and ethical considerations related to 4CMenB immunization, particularly because routine recommendations and funding are currently in place for vaccination against meningococcal serogroups that cause significantly less disease in Canada than MenB. Broadly, the goals are to assist individual practitioners in advocating the benefits of 4CMenB vaccination to parents, and to counterbalance recommendations from the National Advisory Committee on Immunization and the Canadian Paediatric Society. PMID- 26361486 TI - Improving public health policy through infection transmission modelling: Guidelines for creating a Community of Practice. AB - BACKGROUND: Despite significant research efforts in Canada, real application of modelling in public health decision making and practice has not yet met its full potential. There is still room to better address the diversity of the Canadian population and ensure that research outcomes are translated for use within their relevant contexts. OBJECTIVES: To strengthen connections to public health practice and to broaden its scope, the Pandemic Influenza Outbreak Research Modelling team partnered with the National Collaborating Centre for Infectious Diseases to hold a national workshop. Its objectives were to: understand areas where modelling terms, methods and results are unclear; share information on how modelling can best be used in informing policy and improving practice, particularly regarding the ways to integrate a focus on health equity considerations; and sustain and advance collaborative work in the development and application of modelling in public health. METHOD: The Use of Mathematical Modelling in Public Health Decision Making for Infectious Diseases workshop brought together research modellers, public health professionals, policymakers and other experts from across the country. Invited presentations set the context for topical discussions in three sessions. A final session generated reflections and recommendations for new opportunities and tasks. CONCLUSIONS: Gaps in content and research include the lack of standard frameworks and a glossary for infectious disease modelling. Consistency in terminology, clear articulation of model parameters and assumptions, and sustained collaboration will help to bridge the divide between research and practice. PMID- 26361487 TI - Seroprevalences of hepatitis B virus and hepatitis C virus among participants of an Asian health fair in the Lower Mainland, British Columbia. AB - BACKGROUND: The seroprevalences of hepatitis B virus (HBV) and hepatitis C virus (HCV) are 0.4% and 0.8%, respectively, in Canada, but varying rates have been reported in different populations. OBJECTIVES: To determine the seroprevalences of HBV and HCV among attendees of an Asian health fair in the Lower Mainland, British Columbia, as well as to correlate questionnaire answers regarding vaccination status to serological profiles. METHODS: Attendees at an Asian health fair were invited to participate in the present study on a voluntary basis. They provided answers to a questionnaire including ethnicity and vaccination status. Blood was then drawn for HBV and HCV serology. Active HBV was defined as HBV surface antigen (HBsAg) positive while HCV seroprevalence was defined as HCV antibody reactive. Previous exposure to HBV was defined as HBV core antibody (anti-HBc) positive and HBsAg negative. Nonimmunity was defined as anti-HBc negative and HBV surface antibody negative. Only those with correct demographic information matched to serological results were included in the study. RESULTS: There were 192 consenting attendees of the fair, of whom 112 were included in the study. Of the participants, 91% were Chinese. Active HBV infection was found in three participants (2.7% [95% CI 0.6% to 7.6%]) and HCV infection was found in two participants (1.8% [95% CI 0.2% to 6.3%]). More than 40% of participants had been previously exposed to HBV (42% [95% CI 33% to 51%]). Almost 20% demonstrated nonimmunity to HBV (19% [95% CI 12% to 27%]). There was significant discordance when questionnaire answers regarding vaccination status were compared with serological profiles. CONCLUSION: The seroprevalences of HBV and HCV in this cohort were 2.7% and 1.8%, respectively - higher than nationally reported rates. Our results highlight that the lack of knowledge of HBV infection and vaccination status remains a significant clinical issue in the Asian community of British Columbia. PMID- 26361488 TI - Usefulness of previous methicillin-resistant Staphylococcus aureus screening results in guiding empirical therapy for S aureus bacteremia. AB - BACKGROUND: Staphylococcus aureus bacteremia (SAB) is an important infection. Methicillin-resistant S aureus (MRSA) screening is performed on hospitalized patients for infection control purposes. OBJECTIVE: To assess the usefulness of past MRSA screening for guiding empirical antibiotic therapy for SAB. METHODS: A retrospective cohort study examined consecutive patients with confirmed SAB and previous MRSA screening swab from six academic and community hospitals between 2007 and 2010. Diagnostic test properties were calculated for MRSA screening swab for predicting methicillin resistance of SAB. RESULTS: A total of 799 patients underwent MRSA screening swabs before SAB. Of the 799 patients, 95 (12%) had a positive and 704 (88%) had a negative previous MRSA screening swab. There were 150 (19%) patients with MRSA bacteremia. Overall, previous MRSA screening swabs had a positive likelihood ratio of 33 (95% CI 18 to 60) and a negative likelihood ratio of 0.45 (95% CI 0.37 to 0.54). Diagnostic accuracy differed depending on mode of acquisition (ie, community-acquired, nosocomial or health care-associated infection) (P<0.0001) and hospital (P=0.0002). At best, for health care associated infection, prior MRSA screening swab had a positive likelihood ratio of 16 (95% CI 9 to 28) and a negative likelihood ratio of 0.27 (95% CI 0.17 to 0.41). CONCLUSIONS: A negative prior MRSA screening swab cannot reliably rule out MRSA bacteremia and should not be used to guide empirical antibiotic therapy for SAB. A positive prior MRSA screening swab greatly increases likelihood of MRSA, necessitating MRSA coverage in empirical antibiotic therapy for SAB. PMID- 26361489 TI - Identifying factors associated with changes in CD4(+) count in HIV-infected adults in Saskatoon, Saskatchewan. AB - OBJECTIVE: To assess the impact of clinical and social factors unique to HIV infected adults in Saskatoon, Saskatchewan, regarding the rate of CD4(+) count change, and to identify factors associated with a risk of CD4(+) count decline. METHODS: A retrospective longitudinal cohort study from medical chart reviews at two clinics was conducted in Saskatoon. Univariate and multivariate linear mixed effects models were used to assess the impact of selected factors on CD4(+) count change. RESULTS: Four hundred eleven HIV-infected patients were identified from January 1, 2003 to November 30, 2011. Two hundred eighteen (53%) were male, mean (+/- SD) age was 35.6 +/-10.1 years, 257 (70.8%) were First Nations or Metis, 312 (80.2%) were hepatitis C virus (HCV) coinfected and 300 (73.3%) had a history of injection drug use (IDU). In univariate models, age, ethnicity, HCV, IDU, antiretroviral therapy and social assistance were significant. Using ethnicity, HCV and IDU, three multivariate models (models 1, 2, 3) were built due to high correlation. First Nations or Metis ethnicity, HCV coinfection and a history of IDU were associated with significantly lower CD4(+) counts in multivariate models. Older age and social assistance were associated with significantly lower CD4(+) counts in models 1 and 3. Age was marginally significant in model 2 (P=0.055). Not prescribed antiretroviral therapy was associated with a significantly negative CD4(+) count slope in all multivariate models. CONCLUSION: The unique epidemiology of this HIV-infected population may be contributing to CD4(+) count change. Increased attention and resources focused on this high-risk population are needed to prevent disease progression and to improve overall health and quality of life. PMID- 26361490 TI - Pasteurella multocida non-native joint infection after a dog lick: A case report describing a complicated two-stage revision and a comprehensive review of the literature. AB - Prosthetic joint infections (PJIs) are commonly caused by pathogens such as Staphylococcus aureus and coagulase-negative staphylococci; however, other microbial etiologies and specific risk factors are increasingly recognized. Pasteurella multocida is a Gram-negative coccobacillus that is part of the normal oral flora in many animals, and is particularly common in dogs and cats. PJIs caused by P multocida have been reported only rarely in the literature and typically occur in the context of an animal bite or scratch. The present article describes a P multocida joint infection that occurred after a dog lick and complicated a two-stage revision arthroplasty. A comprehensive review of the literature regarding P multocida PJIs follows. PMID- 26361491 TI - A confirmed case of toxic shock syndrome associated with the use of a menstrual cup. AB - Menstrual cups have been reported to be an acceptable substitute for tampons. These flexible cups have also been reported to provide a sustainable solution to menstrual management, with modest cost savings and no significant health risk. The present article documents the first case of toxic shock syndrome associated with the use of a menstrual cup in a woman 37 years of age, using a menstrual cup for the first time. Toxic shock syndrome and the literature on menstrual cups is reviewed and a possible mechanism for the development of toxic shock syndrome in the patient is described. PMID- 26361492 TI - Avian influenza A (H5N1) infection with respiratory failure and meningoencephalitis in a Canadian traveller. AB - In an urban centre in Alberta, an otherwise healthy 28-year-old woman presented to hospital with pleuritic chest and abdominal pain after returning from Beijing, China. After several days, this was followed by headache, confusion and, ultimately, respiratory failure, coma and death. Microbiology yielded influenza A subtype H5N1 from various body sites and neuroimaging was consistent with meningoencephalitis. While H5N1 infections in humans have been reported in Asia since 1997, this is the first documented case of H5N1 influenza in the Western Hemisphere. The present case demonstrated the typical manifestation of H5N1 influenza but, for the first time, also confirmed previous suggestions from human and animal studies that H5N1 is neurotropic and can manifest with neurological symptoms and meningoencephalitis. PMID- 26361493 TI - Assessment of whole-body vibration exposures and influencing factors for quarry haul truck drivers and loader operators. AB - To further assess vibration exposure on haul trucks (HTs) and front-end wheel loaders (FELs), follow-up investigations were conducted at two US crushed stone operations. The purpose was to: 1) evaluate factors such as load/no-load conditions, speed, load capacity, vehicle age, and seat transmissibility relative to vibration exposure; 2) compare exposure levels with existing ISO/ANSI and EUGPG guidelines. Increasing HT speed increased recorded vibration at the chassis and seat as expected. Neither vehicle load nor vehicle speed increased transmissibility. Increasing HT size and age did show transmissibility decreasing. HT dominant-axis wRMS levels (most often the y-axis, lateral or side to-side direction) were predominantly within the health guidance caution zone (HGCZ). However, several instances showed vibration dose value (VDV) above the exposure limit value (ELV) for the ISO/ANSI guidelines. VDV levels (all dominant x-axis or fore-aft) were within and above the HGCZ for the EUGPG and above the HGCZ for ISO/ANSI guidelines. PMID- 26361494 TI - Low breastfeeding rates and body mass index in Danish children of women with gestational diabetes mellitus. AB - BACKGROUND: Offspring from women with gestational diabetes mellitus (GDM) are at risk for later overweight, and the aim of treatment regimens is to normalize their prognosis. While the general concept is that breastfeeding is protective and should be promoted, some studies report increased levels of insulin and glucose in breast milk of women with diabetes, possibly increasing risks to the children. Previous studies may have low retention rates or mix GDM and pre-GDM, and often knowledge of confounders like maternal body mass index (BMI), level of hyperglycemia and feeding patterns is lacking. Data on breastfeeding rates, growth patterns and their associations are important to optimize future strategies among offspring from women with GDM managed by diet. METHODS: Based on 10.730 births, a cohort of 131 singletons of Danish women with GDM managed by diet was defined. Data on feeding patterns, offspring length, weight and head circumference were obtained at the initial admission and from examinations by the general practitioner at five weeks and at five months postpartum. Breastfeeding rates were described in relation to neonatal and maternal characteristics and compared to national rates, while anthropometric data were compared to reference standards. The association between breastfeeding and offspring growth was analysed with and without correcting for confounding. RESULTS: More than 99 % of the cohort contributed to anthropometric data, while data on feeding patterns were available for 96-98 %. Of mothers, 8 % did not initiate breastfeeding and the rate of fully breastfeeding at five weeks and at five months of age were 61 % and 18 %, respectively, which is considerably lower than generally reported in Denmark. Lowest breastfeeding rates were seen following prelabour Caesarean delivery. Complementary feeding was introduced earlier than recommended among 11 %. At the age of five weeks and at five months, children had grown longer and had lower BMI than expected from Danish and World Health Organization references. In the study periods, breastfeeding was significantly associated with lower BMI. CONCLUSION: Despite lower breastfeeding rates than normally reported in Denmark, offspring BMI at the age of five months were low. Still new initiatives to promote breastfeeding among Danish women with GDM should be considered. PMID- 26361495 TI - Chemoenzymatic Kinetic resolution of (R)-malathion in aqueous media. AB - BACKGROUND: Malathion (R,S)-diethyl-2 [(dimethoxyphosphorothioyl)sulfanyl]butanedioate is a chiral organophosphorus compound used widely as pesticide for suppression of harmful insects such as mosquitoes. It is well known that in biological systems (R)-malathion is the active enantiomer, therefore a sustainable approach could be the use of only the biologically active enantiomer. The resolution of the commercial racemic mixture to obtain the pure active enantiomer combined with a recycling of the undesired enantiomer through a racemization process could be an attractive alternative to reduce the environmental impact of this pesticide. Thus, this work evaluates the use of four commercially available lipases for enantioselective hydrolysis and separation of malathion enantiomers from the commercial racemic mixture. RESULTS: Several lipases were methodologically assessed, considering parameters such as enzyme concentration, temperature and reaction rates. Among them, Candida rugosa lipase exhibited the best performance, in terms of enantioselectivity, E = 185 (selective to the (S)-enantiomer). In this way, the desired unreacted (R) enantiomer was recovered in a 49.42 % yield with an enantiomeric excess of 87 %. The monohydrolized (S)-enantiomer was recovered and racemized in basic media, followed by esterification to obtain the racemic malathion, which was recycled. In this way, an enantioenriched mixture of (R)-malathion was obtained with a conversion of 65.80 % considering the recycled (S)-enantiomer. CONCLUSION: This work demonstrated the feasibility of exploiting Candida rugosa lipase to kinetically resolve racemic malathion through an environmentally friendly recycling of the undesired (S)-enantiomer. Graphical AbstractLipase catalyzed enantioselective resolution of (R)-malathion in aqueous solvent. PMID- 26361496 TI - An objective measure of hyperactivity aspects with compressed webcam video. AB - BACKGROUND: Objective measures of physical activity are currently not considered in clinical guidelines for the assessment of hyperactivity in the context of Attention-Deficit/Hyperactivity Disorder (ADHD) due to low and inconsistent associations between clinical ratings, missing age-related norm data and high technical requirements. METHODS: This pilot study introduces a new objective measure for physical activity using compressed webcam video footage, which should be less affected by age-related variables. A pre-test established a preliminary standard procedure for testing a clinical sample of 39 children aged 6-16 years (21 with a clinical ADHD diagnosis, 18 without). Subjects were filmed for 6 min while solving a standardized cognitive performance task. Our webcam video-based video-activity score was compared with respect to two independent video-based movement ratings by students, ratings of Inattentiveness, Hyperactivity and Impulsivity by clinicians (DCL-ADHS) giving a clinical diagnosis of ADHD and parents (FBB-ADHD) and physical features (age, weight, height, BMI) using mean scores, correlations and multiple regression. RESULTS: Our video-activity score showed a high agreement (r = 0.81) with video-based movement ratings, but also considerable associations with age-related physical attributes. After controlling for age-related confounders, the video-activity score showed not the expected association with clinicians' or parents' hyperactivity ratings. CONCLUSIONS: Our preliminary conclusion is that our video-activity score assesses physical activity but not specific information related to hyperactivity. The general problem of defining and assessing hyperactivity with objective criteria remains. PMID- 26361497 TI - Highlights from the 5th Symposium on Biological Data Visualization: Part 2. PMID- 26361498 TI - miRTarVis: an interactive visual analysis tool for microRNA-mRNA expression profile data. AB - BACKGROUND: MicroRNAs (miRNA) are short nucleotides that down-regulate its target genes. Various miRNA target prediction algorithms have used sequence complementarity between miRNA and its targets. Recently, other algorithms tried to improve sequence-based miRNA target prediction by exploiting miRNA-mRNA expression profile data. Some web-based tools are also introduced to help researchers predict targets of miRNAs from miRNA-mRNA expression profile data. A demand for a miRNA-mRNA visual analysis tool that features novel miRNA prediction algorithms and more interactive visualization techniques exists. RESULTS: We designed and implemented miRTarVis, which is an interactive visual analysis tool that predicts targets of miRNAs from miRNA-mRNA expression profile data and visualizes the resulting miRNA-target interaction network. miRTarVis has intuitive interface design in accordance with the analysis procedure of load, filter, predict, and visualize. It predicts targets of miRNA by adopting Bayesian inference and MINE analyses, as well as conventional correlation and mutual information analyses. It visualizes a resulting miRNA-mRNA network in an interactive Treemap, as well as a conventional node-link diagram. miRTarVis is available at http://hcil.snu.ac.kr/~rati/miRTarVis/index.html. CONCLUSIONS: We reported findings from miRNA-mRNA expression profile data of asthma patients using miRTarVis in a case study. miRTarVis helps to predict and understand targets of miRNA from miRNA-mRNA expression profile data. PMID- 26361499 TI - PathwayMatrix: visualizing binary relationships between proteins in biological pathways. AB - BACKGROUND: Molecular activation pathways are inherently complex, and understanding relations across many biochemical reactions and reaction types is difficult. Visualizing and analyzing a pathway is a challenge due to the network size and the diversity of relations between proteins and molecules. RESULTS: In this paper, we introduce PathwayMatrix, a visualization tool that presents the binary relations between proteins in the pathway via the use of an interactive adjacency matrix. We provide filtering, lensing, clustering, and brushing and linking capabilities in order to present relevant details about proteins within a pathway. CONCLUSIONS: We evaluated PathwayMatrix by conducting a series of in depth interviews with domain experts who provided positive feedback, leading us to believe that our visualization technique could be helpful for the larger community of researchers utilizing pathway visualizations. PathwayMatrix is freely available at https://github.com/CreativeCodingLab/PathwayMatrix. PMID- 26361500 TI - Extended LineSets: a visualization technique for the interactive inspection of biological pathways. AB - BACKGROUND: Biologists make use of pathway visualization tools for a range of tasks, including investigating inter-pathway connectivity and retrieving details about biological entities and interactions. Some of these tasks require an understanding of the hierarchical nature of elements within the pathway or the ability to make comparisons between multiple pathways. We introduce a technique inspired by LineSets that enables biologists to fulfill these tasks more effectively. RESULTS: We introduce a novel technique, Extended LineSets, to facilitate new explorations of biological pathways. Our technique incorporates intuitive graphical representations of different levels of information and includes a well-designed set of user interactions for selecting, filtering, and organizing biological pathway data gathered from multiple databases. CONCLUSIONS: Based on interviews with domain experts and an analysis of two use cases, we show that our technique provides functionality not currently enabled by current techniques, and moreover that it helps biologists to better understand both inter pathway connectivity and the hierarchical structure of biological elements within the pathways. PMID- 26361501 TI - MoFlow: visualizing conformational changes in molecules as molecular flow improves understanding. AB - BACKGROUND: Current visualizations of molecular motion use a Timeline-analogous representation that conveys "first the molecule was shaped like this, then like this...". This scheme is orthogonal to the Pathline-like human understanding of motion "this part of the molecule moved from here to here along this path". We present MoFlow, a system for visualizing molecular motion using a Pathline analogous representation. RESULTS: The MoFlow system produces high-quality renderings of molecular motion as atom pathlines, as well as interactive WebGL visualizations, and 3D printable models. In a preliminary user study, MoFlow representations are shown to be superior to canonical representations for conveying molecular motion. CONCLUSIONS: Pathline-based representations of molecular motion are more easily understood than timeline representations. Pathline representations provide other advantages because they represent motion directly, rather than representing structure with inferred motion. PMID- 26361502 TI - ReactionFlow: an interactive visualization tool for causality analysis in biological pathways. AB - BACKGROUND: Molecular and systems biologists are tasked with the comprehension and analysis of incredibly complex networks of biochemical interactions, called pathways, that occur within a cell. Through interviews with domain experts, we identified four common tasks that require an understanding of the causality within pathways, that is, the downstream and upstream relationships between proteins and biochemical reactions, including: visualizing downstream consequences of perturbing a protein; finding the shortest path between two proteins; detecting feedback loops within the pathway; and identifying common downstream elements from two or more proteins. RESULTS: We introduce ReactionFlow, a visual analytics application for pathway analysis that emphasizes the structural and causal relationships amongst proteins, complexes, and biochemical reactions within a given pathway. To support the identified causality analysis tasks, user interactions allow an analyst to filter, cluster, and select pathway components across linked views. Animation is used to highlight the flow of activity through a pathway. CONCLUSIONS: We evaluated ReactionFlow by providing our application to two domain experts who have significant experience with biomolecular pathways, after which we conducted a series of in-depth interviews focused on each of the four causality analysis tasks. Their feedback leads us to believe that our techniques could be useful to researchers who must be able to understand and analyze the complex nature of biological pathways. ReactionFlow is available at https://github.com/CreativeCodingLab/ReactionFlow. PMID- 26361503 TI - Prediction of relevant biomedical documents: a human microbiome case study. AB - BACKGROUND: Retrieving relevant biomedical literature has become increasingly difficult due to the large volume and rapid growth of biomedical publication. A query to a biomedical retrieval system often retrieves hundreds of results. Since the searcher will not likely consider all of these documents, ranking the documents is important. Ranking by recency, as PubMed does, takes into account only one factor indicating potential relevance. This study explores the use of the searcher's relevance feedback judgments to support relevance ranking based on features more general than recency. RESULTS: It was found that the researcher's relevance judgments could be used to accurately predict the relevance of additional documents: both using tenfold cross-validation and by training on publications from 2008-2010 and testing on documents from 2011. CONCLUSIONS: This case study has shown the promise for relevance feedback to improve biomedical document retrieval. A researcher's judgments as to which initially retrieved documents are relevant, or not, can be leveraged to predict additional relevant documents. PMID- 26361504 TI - Hepatic hemangioma -review-. AB - Hepatic hemangiomas are benign tumors of the liver consisting of clusters of blood-filled cavities, lined by endothelial cells, fed by the hepatic artery. The vast majority of HH are asymptomatic, most often being discovered incidentally during imaging investigations for various unrelated pathologies. Typical hemangiomas, the so-called capillary hemangiomas, range from a few mm to 3 cm, do not increase in size over time and therefore are unlikely to generate future symptomatology. Small (mm-3 cm) and medium (3 cm-10 cm) hemangiomas are well defined lesions, requiring no active treatment beside regular follow-ups. However, the so-called giant liver hemangiomas, of up to 10 cm (most commonly) and even 20+ cm in size (according to occasional reports) can, and usually will develop symptoms and complications that require prompt surgical intervention or other kind of therapy. HH belong to the class of hepatic "incidentalomas", so called because they are diagnosed incidentally, on imaging studies performed as routine examinations or for other reasons than the evaluation of a possible liver mass. Less than half of HH present with overt clinical symptoms, consisting, most often, of upper abdominal pain (this is usually the case for large lesions, which cause the distension of Glisson's capsule). Hepatic hemangiomas require a careful diagnosis to differentiate from other focal hepatic lesions, co-occurring diagnoses are also possible. PMID- 26361505 TI - Recurrence after hepatic resection in colorectal cancer liver metastasis -Review article-. AB - The outcomes and management of colorectal liver metastasis have undergone many changes. The incidence of recurrence after liver resection for hepatic metastasis remains very high. Liver resection, which provides the only curative treatment, is believed to have improved the long-term outcome of these patients. However, the management and outcomes of patients with colorectal liver metastasis have greatly improved in the last decade, suggesting that the current use of aggressive multimodality treatments, including surgical resection combined with modern chemotherapeutic regimens, effectively prolong the life expectancy of these patients. PMID- 26361506 TI - Neutrophil Gelatinase Associated Lipocalin (NGAL) - a biomarker of renal dysfunction in patients with liver cirrhosis: Do we have enough proof? AB - RATIONALE: Renal dysfunction has a serious impact on the natural evolution of liver cirrhosis. Treatment and prognosis may be improved if an early diagnosis could be established, and specific therapeutic interventions would be applied. Although RIFLE and AKIN classifications have been successfully implemented in the clinical practice of Nephrology and Intensive Care Units, these did not provide major improvements in patients with liver cirrhosis. In the last decade, various biomarkers of kidney injury have been assessed, and Neutrophil Gelatinase Associated Lipocalin (NGAL) is one of the most promising and most studied novel biomarker. OBJECTIVE: To offer a brief evaluation on current data on the utility of this biomarker in patients with liver cirrhosis. METHODS AND RESULTS: We have searched through current literature and analyzed all significant full text articles on this topic. DISCUSSIONS: NGAL and other new kidney injury molecules may be useful in patients with liver cirrhosis, particularly in identifying structural kidney dysfunction, but larger validation studies to confirm this observation are needed. PMID- 26361508 TI - Burning mouth syndrome: controversial place as a symptom of Oro-dental pathology. AB - As defined by WHO experts, disease involves a change of the physical, mental and social welfare, generating chronic stress condition if unresolved. One of the symptoms almost constantly found in any condition is pain. This feeling manifests differently depending on the subjective perception. The burning mouth syndrome (BMS) is included in such a framework. The BMS is considered as one of the characteristic states of chronic stress syndromes associated with nonspecific clinical manifestations and requires special medical attention in terms of assessing and treating the condition. However, the insufficient knowledge of its etiopathogenic mechanisms requires comprehensive research undertaken on such a subject. PMID- 26361507 TI - Clinical evolutional aspects of chronic subdural haematomas - literature review. AB - Apparently trivial, one of the most frequent pathologies in neurosurgical practice, chronic subdural haematoma, continues to be a challenge for the neurosurgeons both from the therapeutic and postoperatory complications point of view, taking into account that it is frequently met in elders, who usually present a complex pathology. The fact that, by definition, there is a latent period between the moment the brain injury, usually minor, occurs and the appearance of clinical symptomatology, frequently makes the trauma be ignored, this complicating the diagnosis and most of the times delaying the application of the adequate treatment. Developing slowly in time, in weeks or months, the aspect that chronic subdural haematoma usually occurs in elders should not be neglected, its clinical symptomatology often debuting with memory and attention disorders, so that the patient is usually referred to psychiatrists or neurologists, only a paraclinical investigation (CT scan or MRI) being able to establish the diagnosis. Even the appearance of the lateral signs is subjected to many diagnosis confusions because patients deny the existence of a trauma in over 50% of the cases. PMID- 26361509 TI - On reactive oxygen species measurement in living systems. AB - Studies devoted to the detection and measurement of free radicals in biological systems generally generated accepted methods of reactive oxygen species (ROS) level analysis. When out of control, ROS induces tissue damage, chronic inflammatory processes and cellular functional disturbances. Aerobic organisms have adapted to defense against ROS aggression by developing potent antioxidant mechanisms. Recent advances in ROS measurement methodology allow the study of ROS biology at a previously unachievable level of precision. However, their high activity, very short life span and extremely low concentration, make ROS measurement a challenging subject for researchers. PMID- 26361511 TI - Solutions for reducing lawsuits in orthopedic surgery by using psychology and IT technology. AB - Orthopedic surgery is among the top 5 medical specialties with an increased risk of facing a lawsuit. A large part of medical malpractice claims are due to poor communication between physician and patient; therefore, by addressing this issue and implementing psychological methods as well as IT solutions, a reduction in the incidence of medical lawsuits can be achieved. Some of these solutions include implementing and applying psychometric tools such as the SF-36 and SCL 90R tests, creating virtual information hubs for the patient, and establishing efficient communication methods by using IT technology between physician and patient. PMID- 26361510 TI - Oxidative stress and alopecia areata. AB - Alopecia areata (AA) is an inflammatory and autoimmune disease presenting with non-scarring hair loss. The aethiopathogenesis of alopecia areata is unclear and many factors including autoimmunity, genetic predisposition, emotional and environmental stress are thought to play important roles in its development. Antioxidant/ oxidant balance perturbation is a common feature in autoimmune, emotional and environmental stress. Therefore, our paper discusses the implications of oxidative stress in alopecia areata. PMID- 26361512 TI - Non-invasive brain stimulation in early rehabilitation after stroke. AB - The new tendency in rehabilitation involves non-invasive tools that, if applied early after stroke, promote neurorecovery. Repetitive transcranial magnetic stimulation and transcranial direct current stimulation may correct the disruption of cortical excitability and effectively contribute to the restoration of movement and speech. The present paper analyses the results of non-invasive brain stimulation (NIBS) trials, highlighting different aspects related to the repetitive transcranial magnetic stimulation frequency, transcranial direct current stimulation polarity, the period and stimulation places in acute and subacute ischemic strokes. The risk of adverse events, the association with motor or language recovery specific training, and the cumulative positive effect evaluation are also discussed. PMID- 26361513 TI - Cutaneous adverse reactions specific to epidermal growth factor receptor inhibitors. AB - Classical antineoplastic therapy is encumbered by extensively studied adverse reactions, most often of systemic nature. The emergence of new generations of anticancer treatments, including epidermal growth factor receptor inhibitors, besides improving the response to treatment and the survival rate, is accompanied by the occurrence of new specific side effects, incompletely studied. These side effects are most often cutaneous (hand foot syndrome, acneiform reactions), and in some cases are extremely severe, requiring dose reduction or drug discontinuation. The prevention of the cutaneous adverse effects and their treatment require a close collaboration between the oncologist and the dermatologist. The occurrence of some of these skin adverse effects may be a favorable prognostic factor for the response to the cancer treatment and the overall survival. PMID- 26361514 TI - Synergistic approach to patient dialysate. AB - The stress a patient is subjected to during dialysis treatment can be reduced by using a synergetic approach by the medical team. The integration into therapy of the positive psychical resources such as: active positive coping mechanisms, individual or family mental resilience, improvement of the image and self-esteem, better tolerance to frustration can represent an important part in the improvement of the patient's quality of life, determination of a positive approach of the situations both for him and close friends and relatives. PMID- 26361515 TI - Venous versus arterial iron administration in haemodialysis. Influence on erythrocytes antioxidant parameters. AB - Introduction Intravenous iron administration in patients treated by haemodialysis for end stage renal disease can exacerbate oxidative stress by increasing the level of free redox active iron. A way to reduce the impact of iron on oxidative stress in haemodialysis patients may be the administration of iron through arterial extracorporeal circuit. Objective The aim of our study was to compare the influence of iron route of administration (venous versus arterial extracorporeal circuit infusion) on antioxidant parameters in red blood cells of haemodialysis patients in order to clarify if arterial iron administration can have positive impacts related to iron induced oxidative stress. Method Twenty stable patients on regular haemodialysis treatment were selected for the study. They were investigated in a cross-over design at 3 mid-week HD sessions, one week apart, without iron [HD basal] and with either IV infusion of 100mg iron sucrose over the first 20 minutes of HD session, via venous line [HDvenous], or the same solution infused on the arterial extracorporeal circulation [HDarterial]. Blood samples were drawn at 0 min, 40 min and 270 min. Erythrocytes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) activity, non protein thiol levels and total antioxidant capacity (TEAC) were analysed. Conclusion Haemodialysis significantly decreases the total antioxidant activity in erythrocytes. Iron supplementation, through venous or arterial extracorporeal route has no impact on the total antioxidant activity in red blood cells. Venous iron administration increases GPx activity in erythrocytes suggesting increased lipid peroxidation compared with arterial extracorporeal administration. PMID- 26361516 TI - Neurological soft signs in early stage of schizophrenia associated with obsessive compulsive disorder. AB - BACKGROUND: Given that the obsessive-compulsive disorder (OCD) occurs with a much higher frequency in schizophrenia than in the general population, and, both schizophrenia and OCD are presumed to be neurodevelopmental disorders, the hypothesis of a distinct subtype of schizophrenia, the "schizo-obsessive" one, was raised. AIM: Considering the neurological soft signs as neurobiological markers in schizophrenia, the aim of this study was to verify the hypothesis of the existence of this "schizo-obsessive" endophenotype of schizophrenia, by using the Neurological Evaluation Scale (NES) in patients with schizophrenia. METHOD: The study was conducted in a transversal manner and consisted of the assessment of 64 patients with the maximum age of 26 years, who fulfilled the DSM IV-TR criteria of schizophrenia and/ or OCD, the assessment performed both from the social-demographic view, as well as neurologic, by means of the NES scale. RESULTS: Patients with schizophrenia and OCD proved to have, a significant family history from a static point of view, more loaded by affective disorders, but also by schizophrenia and OCD spectrum disorders, compared to pure schizophrenics. They also proved to have a significant higher educational level and a better occupational functioning than those schizophrenic patients without OCD, despite the similarity of the number of hospitalizations episodes or the disease duration to date. Ratings on the NES scale differentiate the group of patients with schizophrenia and OCD as having the highest scores on all subscales, scores much closer to those obtained by the group of patients with schizophrenia only, the only difference with statistical significance being recorded on the sequencing subscale of complex motor acts. The analysis of cluster through linear discriminant analysis allowed the classification of patients in the 3 groups with a probability of 89.06% and 76.56% for cross-validation. DISCUSSION: The results regarding neurological soft signs suggest that the presence of OCD in schizophrenic patients is due to peculiarities in fronto-basal ganglia circuits with possible origins in neurodevelopmental abnormalities. We considered that the early detection of neurological soft signs and their dynamic monitoring could provide useful information on the evolution of schizophrenia. Future research should take into account larger groups of patients to investigate the relationship between neurological soft signs and brain neuroimaging data, as well as the results provided by neuropsychological investigations customed in this subgroup of schizophrenia. PMID- 26361517 TI - Glycemic profile in patients with acromegaly treated with somatostatin analogue. AB - HYPOTHESIS: The growth hormone (GH) excess displayed in acromegaly induces insulin resistance up to diabetes mellitus (DM). The somatostatin analogues (as octreotide LAR) are useful in controlling the GH levels but disturbances of glucose metabolism might be seen. OBJECTIVE: This study evaluates the acromegalic glycemic profile under octreotide. METHODS & RESULTS: Out of the total number of patients (N=34) diagnosed with active acromegaly, only some were followed (N=25; male/ female ratio: 6/ 19; mean age: 51.8 years) by testing GH, IGF1 (Insulin Growth Factor 1), basal glucose and oral glucose tolerance test (OCGTT) at baseline, 6 and 12 months under Octreotide (first 6 months with 20 mg/ 28 days + 6 months with 30 mg/ 28 days). Pre-treatment values were 17.6% of patients had DM, 14.7% - impaired glucose tolerance, 26.5% - impaired fasting glucose, and 41.2% - normal assays. From the statistical point of view, the DM patients were significantly older and had higher GH levels than the acromegalic without glycaemia disturbances. They did not achieve significant changes in basal blood glucose and glycated hemoglobin after 6 months, neither after 12 months. After 6 months, there were no significant changes in basal glycaemia in patients with normal baseline glycaemia but 2-hours OGTT glucose values were significantly lower than initially (82.35 mg/ dl vs. 93 mg/ dl, p=0.005) consistent with reduced levels of GH and IGF1. After 12 months, both basal and 2-hours glucose levels in OGTT were similar to baseline despite the significant lower GH (3.3 vs. 6.61 ng/ mL, p=0.003) and IGF1 (332 vs. 713 ng/ mL, p=0.001). CONCLUSIONS: Octreotide therapy induces an improvement in glycemic profile in patients with active acromegaly without diabetes mellitus consistent with decreased levels of GH and IGF1. In patients with diabetes, partial control of glucose metabolism is due to inadequate suppression of GH and IGF1 after one year of treatment. PMID- 26361518 TI - Minimally invasive-percutaneous surgery - recent developments of the foot surgery techniques. AB - Percutaneous techniques are currently more and more used in many surgical procedures on the soft tissues and bones of the foot. Practical advantages include lower complication rates and faster recovery times. Potential disadvantages are related to the need for specific equipment and extensive learning curve. One of the most frequent techniques involves a combination of chevron osteotomy of the first metatarsal with osteotomy of the first phalanx, both internally fixated. Lateral metatarsal misalignment and toe deformities can also be addressed by percutaneous treatment, with lower morbidity rates than open techniques. The most commonly performed percutaneous procedures are described, with their current indications, outcomes, and recent developments. PMID- 26361519 TI - Special forms in twin pregnancy - asymmetric conjoined twins. AB - Twin pregnancies generally represent a high-risk pregnancy. However, monozygous twins are real challenges for obstetricians due to the complications that may occur. Among the particular cases of monozygous twins in the University Emergency Hospital of Bucharest, Department of Obstetrics and Gynecology, a monochorial monoamniotic pregnancy with conjoined twins has been described. These particular medical circumstances require a deeper understanding of the vascular anatomical particularities. An accurate diagnosis implies a most detailed description of the morphological dynamics of the fetuses with the study of the impact of the vascular anomaly on their development so that the maximum chances of survival and the best outcome for the viable fetus can be obtained. The diagnosis of the most frequently associated anomalies is also extremely important. PMID- 26361521 TI - Errata. PMID- 26361520 TI - Evaluation of adherence to anti-osteoporosis treatment from the socio-economic context. AB - Osteoporosis is a disease characterized by the reduction of the bone mass and the modification of the bone architecture, which leads to the risk of fracture of the fragile bones, this being the main clinical consequence of the disease. At the same time, osteoporosis is not only a problem by itself, but it is very important from the point of view of the consequences it may produce. Among its consequences, fractures should be mentioned especially in elders, their presence finally leading to an important decrease in the quality of life or even to death. Osteoporosis affects a high amount of persons, preponderantly elders, being considered a very important problem as the society we are talking about deals with the problem of aging. Socio-economical factors and their impact in the development of different pathologies have been seriously analyzed, especially by the western school of medicine. The aim of the current study is to evaluate the adherence to the treatment for osteoporosis of patients diagnosed with osteoporosis or in whom this diagnosis was taken into consideration by the physician, according to some characteristics identified as being the most relevant by a group of specialists. 210 patients were evaluated in this study during January 2011 and December 2013. This study highlighted the way patients with a real or presumptive diagnosis of osteoporosis adhere to the treatment for this disease according to the conditions considered relevant by a team of rheumatologists. It is important to notice that, still from the beginning, once the duration of the disease grows, patients become more and more conscious of the seriousness of the disease and more and more of them adhere to the treatment. PMID- 26361522 TI - HIV Testing and HIV Serostatus-Specific Sexual Risk Behaviour Among Men Who Have Sex with Men Living in England and Recruited Through the Internet in 2001 and 2008. AB - Using data from two large internet-recruited surveys in England in 2001 and 2008, we examine HIV status-specific patterns of unprotected anal intercourse (UAI). In adjusted comparisons between our 2008 and 2001 samples, there was evidence of a greater proportion of men living with diagnosed HIV, a reduction in sexual partners and in UAI with partners of unknown HIV status among men not tested HIV positive, increases in anal intercourse and UAI among men with diagnosed HIV and an increase in insertive UAI with HIV-positive men among men never tested for HIV. However, we found no evidence for increases in negotiated safety or sero sorting. The data are compatible with a concentration of sexual risk among men with diagnosed HIV, countering an overall trend towards less risk taking among men not tested HIV positive. PMID- 26361524 TI - T Lymphocyte Subsets and Cytokines in Rats Transplanted with Adipose-Derived Mesenchymal Stem Cells and Acellular Nerve for Repairing the Nerve Defects. AB - OBJECTIVE: The aim of this study was to explore the immunity in rats transplanted with adipose-derived mesenchymal stem cells (ADSCs) and acellular nerve (ACN) for repairing sciatic nerve defects. METHODS: ADSCs were isolated from the adipose tissues of Wistar rats. Sprague-Dawley rats were used to establish a sciatic nerve defect model and then divided into four groups, according to the following methods : Group A, allogenic nerve graft; Group B, allograft with ACN; Group C, allograft ADSCs+ACN, and Group D, nerve autograft. RESULTS: At the day before transplantation and 3, 7, 14, and 28 days after transplantation, orbital venous blood of the Sprague-Dawley rats in each group was collected to detect the proportion of CD3(+), CD4(+), and CD8(+) subsets using flow cytometry and to determine the serum concentration of interleukin-2 (IL-2), tumor necrosis factor alpha (TNF-alpha) and interferon-gamma (IFN-gamma) using enzyme-linked immunosorbent assay (ELISA). At each postoperative time point, the proportion of CD3(+), CD4(+), and CD8(+) subsets and the serum concentration of IL-2, TNF alpha, and IFN-gamma in group C were all near to those in group B and group D, in which no statistically significant difference was observed. As compared with group A, the proportion of CD3(+), CD4(+), and CD8(+) subsets and the serum concentration of IL-2, TNF-alpha, and IFN-gamma were significantly reduced in group C (p<0.05). CONCLUSION: The artificial nerve established with ADSCs and ACN has no obvious allograft rejection for repairing rat nerve defects. PMID- 26361523 TI - A Role of Serum-Based Neuronal and Glial Markers as Potential Predictors for Distinguishing Severity and Related Outcomes in Traumatic Brain Injury. AB - OBJECTIVE: Optimal treatment decision and estimation of the prognosis in traumatic brain injury (TBI) is currently based on demographic and clinical predictors. But sometimes, there are limitations in these factors. In this study, we analyzed three central nervous system biomarkers in TBI patients, will discuss the roles and clinical applications of biomarkers in TBI. METHODS: From July on 2013 to August on 2014, a total of 45 patients were included. The serum was obtained at the time of hospital admission, and biomarkers were extracted with centrifugal process. It was analyzed for the level of S-100 beta (S100B), glial fibrillary acidic protein (GFAP), and ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1). RESULTS: This study included 33 males and 12 females with a mean age of 58.5 (19-84) years. TBI patients were classified into two groups. Group A was severe TBI with Glasgow Coma Scale (GCS) score 3-5 and Group B was mild TBI with GCS score 13-15. The median serum concentration of S100B, GFAP, and UCH-L1 in severe TBI were raised 5.1 fold, 5.5 fold, and 439.1 fold compared to mild injury, respectively. The serum levels of these markers correlated significantly with the injury severity and clinical outcome (p<0.001). Increased level of markers was strongly predicted poor outcomes. CONCLUSION: S100B, GFAP, and UCH-L1 serum level of were significantly increased in TBI according to severity and associated clinical outcomes. Biomarkers have potential utility as diagnostic, prognostic, and therapeutic adjuncts in the setting of TBI. PMID- 26361525 TI - Feasibility and Efficacy of Olfactory Protection Using Gelfoam and Fibrin Glue during Anterior Communicating Artery Aneurysm Surgery. AB - OBJECTIVE: Patients treated with surgical clipping for anterior communicating artery (A-com) aneurysm often complain of anosmia, which can markedly impede their quality of life. We introduce a simple and useful technique to reduce postoperative olfactory dysfunction in A-com aneurysm surgery. METHODS: We retrospectively reviewed the medical records of patients who underwent surgical clipping for unruptured aneurysm from 2011-2013 by the same senior attending physician. Since March 2012, olfactory protection using gelfoam and fibrin glue was applied in A-com aneurysm surgery. Therefore we categorized patients in two groups from this time-protected group and unprotected group. RESULTS: Of the 63 enrolled patients, 16 patients showed postoperative olfactory dysfunction including 8 anosmia patients (protected group : unprotected group=1 : 7) and 8 hyposmia patients (protected group : unprotected group=2 : 6). Thirty five patients who received olfactory protection during surgery showed a lower rate of anosmia (p=0.037, OR 10.516, 95% CI 1.159-95.449) and olfactory dysfunction (p=0.003, OR 8.693, 95% CI 2.138-35.356). Superior direction of the aneurysm was also associated with a risk of olfactory dysfunction (p=0.015, OR 5.535, 95% CI 1.390-22.039). CONCLUSION: Superior direction of aneurysm appears associated with postoperative olfactory dysfunction. Olfactory protection using gelfoam and fibrin glue could be a simple, safe, and useful method to preserve olfactory function during A-com aneurysm surgery. PMID- 26361526 TI - Prevalence, Distribution, and Significance of Incidental Thoracic Ossification of the Ligamentum Flavum in Korean Patients with Back or Leg Pain : MR-Based Cross Sectional Study. AB - OBJECTIVE: Thoracic ossification of the ligamentum flavum (OLF) is a relatively rare disease. Because of ambiguous clinical symptom, it is difficult for early diagnosis of OLF and subsequent treatment can be delayed or missed. Therefore, the purpose of this study is to comprehensively assess the prevalence and distribution of thoracic OLF by magnetic resonance imaging (MRI) and coexisting spinal disease in Korean patients with back pain or leg pain. METHODS: The sample included 2134 Korean patients who underwent MRI evaluation for back pain. The prevalence and distribution of thoracic OLF were assessed using lumbar MRI with whole spine sagittal images. Additionally, we examined the presence of coexisting lumbar and cervical diseases. The presence of thoracic OLF as well as clinical parameters such as age, sex, and surgery were retrospectively reviewed. RESULTS: The prevalence of thoracic OLF in total patients was 16.9% (360/2134). The prevalence tended to increase with aging and was higher in women than in men. The lower thoracic segment of T10-11 was the most frequently affected segment. Of the 360 patients with OLF, 31.9% had coexisting herniated thoracic discs at the same level. Approximately 74% of the patients with OLF had coexisting lumbar and cervical disease. Nine (2.5%) of 360 OLF patients underwent surgery for thoracic lesion. CONCLUSION: The prevalenceof thoracic OLF was relatively higher than those of previous reports. And coexisting lumbar and cervical disease were very frequent. Therefore, we should check coexisting spinal diseases and the exact diagnostic localization of ossification besides lumbar disease. PMID- 26361528 TI - Is Routine Repeated Head CT Necessary for All Pediatric Traumatic Brain Injury? AB - OBJECTIVE: Repeated computed tomography (CT) follow up for traumatic brain injury (TBI) patients is often performed. But there is debate the indication for repeated CT scans, especially in pediatric patients. Purpose of our study is to find risk factors of progression on repeated CT and delayed surgical intervention based on the repeated head CT. METHODS: Between March, 2007 and December, 2013, 269 pediatric patients (age 0-18 years) had admitted to our hospital for head trauma. Patients were classified into 8 subgroups according to mechanisms of injury. Types, amount of hemorrhage and amount changes on repeated CT were analyzed as well as initial Glasgow Coma Scale (GCS) scores. RESULTS: Within our cohort of 269 patients, 174 patients received repeat CT. There were progression in the amount of hemorrhage in 48 (27.6%) patients. Among various hemorrhage types, epidural hemorrhage (EDH) more than 10 cc measured in initial CT was found to be at risk of delayed surgical intervention significantly after routine repeated CT with or without neurological deterioration than other types of hemorrhage. Based on initial GCS, severe head trauma group (GCS 3-8) was at risk of delayed surgical intervention after routine repeated CT without change of clinical neurologic status. CONCLUSION: We suggest that the patients with EDH more than 10 cc or GCS below 9 should receive repeated head CT even though absence of significant clinical deterioration. PMID- 26361527 TI - Cervical Stand-Alone Polyetheretherketone Cage versus Zero-Profile Anchored Spacer in Single-Level Anterior Cervical Discectomy and Fusion : Minimum 2-Year Assessment of Radiographic and Clinical Outcome. AB - OBJECTIVE: We compared the clinical and radiographic outcomes of stand-alone polyetheretherketone (PEEK) cage and Zero-Profile anchored spacer (Zero-P) for single level anterior cervical discectomy and fusion (ACDF). METHODS: We retrospectively reviewed 121 patients who underwent single level ACDF within 2 years (Jan 2011-Jan 2013) in a single institute. Total 50 patients were included for the analysis who were evaluated more than 2-year follow-up. Twenty-nine patients were allocated to the cage group (m : f=19 : 10) and 21 for Zero-P group (m : f=12 : 9). Clinical (neck disability index, visual analogue scale arm and neck) and radiographic (Cobb angle-segmental and global cervical, disc height, vertebral height) assessments were followed at pre-operative, immediate post operative, post-3, 6, 12, and 24 month periods. RESULTS: Demographic features and the clinical outcome showed no difference between two groups. The change between final follow-up (24 months) and immediate post-op of Cobb-segmental angle (p=0.027), disc height (p=0.002), vertebral body height (p=0.033) showed statistically better outcome for the Zero-P group than the cage group, respectively. CONCLUSION: The Zero-Profile anchored spacer has some advantage after cage for maintaining segmental lordosis and lowering subsidence rate after single level anterior cervical discectomy and fusion. PMID- 26361529 TI - Radiologic Determination of Corpus Callosum Injury in Patients with Mild Traumatic Brain Injury and Associated Clinical Characteristics. AB - OBJECTIVE: To investigate the incidence of corpus callosum injury (CCI) in patients with mild traumatic brain injury (TBI) using brain MRI. We also performed a review of the clinical characteristics associated with this injury. METHODS: A total of 356 patients in the study were diagnosed with TBI, with 94 patients classified as having mild TBI. We included patients with mild TBI for further evaluation if they had normal findings via brain computed tomography (CT) scans and also underwent brain MRI in the acute phase following trauma. As assessed by brain MRI, CCI was defined as a high-signal lesion in T2 sagittal images and a corresponding low-signal lesion as determined by axial gradient echo (GRE) imaging. Based on these criteria, we divided patients into two groups for further analysis : Group I (TBI patients with CCI) and Group II (TBI patients without CCI). RESULTS: A total of 56 patients were enrolled in this study (including 16 patients in Group I and 40 patients in Group II). Analysis of clinical symptoms revealed a significant difference in headache severity between groups. Over 50% of patients in Group I experienced prolonged neurological symptoms including dizziness and gait disturbance and were more common in Group I than Group II (dizziness : 37 and 12% in Groups I and II, respectively; gait disturbance : 12 and 0% in Groups I and II, respectively). CONCLUSION: The incidence of CCI in patients with mild TBI was approximately 29%. We suggest that brain MRI is a useful method to reveal the cause of persistent symptoms and predict clinical prognosis. PMID- 26361530 TI - Concurrent Ruptured Pseudoaneurysm of the Internal Carotid Artery and Cerebral Infarction as an Initial Manifestation of Polycythemia Vera. AB - The most common neurologic manifestations of polycythemia vera (PV) are cerebral infarction and transient ischemic attacks, while cerebral hemorrhage or intracranial dissection has been rarely associated with PV. Here we report the first case of a 59-year-old patient with intracranial supraclinoid internal carotid artery (ICA) dissection causing cerebral infarction and concomitant subarachnoid hemorrhage due to pseudoaneurysm rupture as clinical onset of PV. This case report discusses the possible mechanism and treatment of this extremely rare condition. PMID- 26361531 TI - Ruptured Total Intrameatal Anterior Inferior Cerebellar Artery Aneurysm. AB - Among the distal anterior inferior cerebellar artery (AICA) aneurysms, a unique aneurysm at the meatal loop inside the internal auditory meatus is extremely rare. The authors report a case of surgically treated total intrameatal AICA aneurysm. A 62-year-old female patient presenting with sudden bursting headache and neck pain was transferred to our department. Computed tomography and digital subtraction angiography showed subarachnoid hemorrhage at the basal, prepontine cistern and an aneurysm of the distal anterior inferior cerebellar artery inside the internal auditory meatus. Surgery was performed by retrosigmoid craniotomy with unroofing of the internal auditory meatus. The aneurysm was identified between the seventh and eighth cranial nerve in the meatus and was removed from the canal and clipped with a small straight Sugita clip. After operation the patient experienced transient facial paresis and tinnitus but improved during follow up. PMID- 26361532 TI - Intracranial Chronic Subdural Hematoma Presenting with Intractable Headache after Cervical Epidural Steroid Injection. AB - Postdural punctural headache (PDPH) following spinal anesthesia is due to intracranial hypotension caused by cerebrospinal fluid (CSF) leakage, and it is occasionally accompanied by an intracranial hematoma. To the best of our knowledge, an intracranial chronic subdural hematoma (CSDH) presenting with an intractable headache after a cervical epidural steroid injection (ESI) has not been reported. A 39-year-old woman without any history of trauma underwent a cervical ESI for a herniated nucleus pulposus at the C5-6 level. One month later, she presented with a severe headache that was not relieved by analgesic medication, which changed in character from being positional to non-positional during the preceding month. Brain magnetic resonance imaging revealed a CSDH along the left convexity. Emergency burr-hole drainage was performed and the headache abated. This report indicates that an intracranial CSDH should be considered a possible complication after ESI. In addition, the event of an intractable and changing PDPH after ESI suggests further evaluation for diagnosis of an intracranial hematoma. PMID- 26361533 TI - Complete Separation of the Vertebral Body Associated with a Schmorl's Node Accompanying Severe Osteoporosis. AB - A Schmorl's node is defined as a simple endplate intravertebral herniation resulting from trauma or idiopathic causes. Although Schmorl's nodes have been considered clinically insignificant, they might indicate an active symptomatic process or cause serious complications. In this study, we report an interesting case of complete separation of a vertebral body caused by an untreated Schmorl's node accompanying severe osteoporosis. To our knowledge, this is the first clinical report in the published literature to evaluate the complete separation of a vertebral body associated with a Schmorl's node. PMID- 26361534 TI - Early Spontaneous Recanalization of Sigmoid Sinus Thrombosis Following a Closed Head Injury in a Pediatric Patient : A Case Report and Review of Literature. AB - Cerebral venous sinus thrombosis (CVST) following a closed head injury in pediatric patients is a rare condition, and an early spontaneous recanalization of this condition is extremely rare. A 10-year-old boy was admitted with a mild, intermittent headache and nausea five days after a bicycle accident. The brain computed tomography showed an epidural hematoma at the right occipital area with pneumocephalus due to a fracture of the occipital skull bone. The brain magnetic resonance imaging and the magnetic resonance venography demonstrated a flow signal loss from the right sigmoid sinus to the right jugular vein. The diagnosis was sigmoid sinus thrombosis, so close observations were selected as a treatment for the patient because of his gradually improving symptoms; however, he complained of vomiting 14 days the after conservative treatment. The patient was readmitted for a further examination of his symptoms. The laboratory and the gastroenterological examinations were normal. Due to concern regarding the worsening of the sigmoid sinus thrombosis, the brain magnetic resonance venography was rechecked and it revealed the recanalization of the venous flow in the sigmoid sinus and in the jugular vein. PMID- 26361535 TI - High-Resolution Magnetic Resonance Imaging of Intracranial Vertebral Artery Dissecting Aneurysm for Planning of Endovascular Treatment. AB - The equipment and techniques associated with magnetic resonance imaging (MRI) have rapidly evolved. The development of 3.0 Tesla MRI has enabled high resolution imaging of the intracranial vessel wall. High-resolution MRI (HRMRI) can yield excellent visualization of both the arterial wall and lumen, thus facilitating the detection of the primary and secondary features of intracranial arterial dissection. In the present report, we describe the manner in which HRMRI affected our endovascular treatment planning strategy in 2 cases with unruptured intracranial vertebral artery dissection aneurysm. HRMRI provides further information about the vessel wall and the lumen of the unruptured intracranial vertebral artery dissecting aneurysm, which was treated by an endovascular approach in the 2 current cases. PMID- 26361536 TI - Valproic Acid-Induced Hyperammonemic Encephalopathy as a Cause of Neurologic Deterioration after Unruptured Aneurysm Surgery. AB - Neurological deficits after brain surgery are not uncommon, and correct and prompt differential diagnosis is essential to initiate appropriate treatment. We describe a patient suffering from loss of consciousness due to hyperammonemia, following valproic acid treatment after surgery for an unruptured cerebral aneurysm. A 57-year-old female patient underwent successful aneurysmal neck clipping to correct an unruptured aneurysm. Her postoperative course was good, and she received anti-epileptic therapy (valproic acid) and a soft diet. Within a few days the patient experienced mental deterioration. Her serum valproic acid reached toxic levels (149.40 mg/L), and serum ammonia was fifteen times the upper normal limit (553 mmol/L; normal range, 9-33 mmol/L). After discontinuation of valproic acid and with conservative treatment, the patient recovered without any complications. Valproate-induced hyperammonemic encephalopathy is an unusual but serious neurosurgical complication, and should not be disregarded as a possible cause of neurological deficits after neurovascular surgery. Early diagnosis is crucial, as discontinuation of valproic acid therapy can prevent serious complications, including death. PMID- 26361537 TI - Phenytoin Induced Erythema Multiforme after Cranial Radiation Therapy. AB - The prophylactic use of phenytoin during and after brain surgery and cranial irradiation is a common measure in brain tumor therapy. Phenytoin has been associated with variety of adverse skin reactions including urticaria, erythroderma, erythema multiforme (EM), Stevens-Johnson syndrome, and toxic epidermal necrolysis. EM associated with phenytoin and cranial radiation therapy (EMPACT) is a rare specific entity among patients with brain tumors receiving radiation therapy while on prophylactic anti-convulsive therapy. Herein we report a 41-year-old female patient with left temporal glial tumor who underwent surgery and then received whole brain radiation therapy and chemotherapy. After 24 days of continous prophylactic phenytoin therapy the patient developed minor skin reactions and 2 days later the patient returned with generalized erythamatous and itchy maculopapuler rash involving neck, chest, face, trunk, extremities. There was significant periorbital and perioral edema. Painful mucosal lesions consisting of oral and platal erosions also occurred and prevented oral intake significantly. Phenytoin was discontinued gradually. Systemic admistration of corticosteroids combined with topical usage of steroids for oral lesions resulted in complete resolution of eruptions in 3 weeks. All cutaneous lesions in patients with phenytoin usage with the radiotherapy must be evoluated with suspicion for EM. PMID- 26361538 TI - Hawthorn ethanolic extracts with triterpenoids and flavonoids exert hepatoprotective effects and suppress the hypercholesterolemia-induced oxidative stress in rats. AB - OBJECTIVES: The current study was aimed to determine the bioactive constituents and biological effects of the Crataegus monogyna ethanolic extracts from bark, leaves and berries on hypercholesterolemia. MATERIALS AND METHODS: Oleanolic acid, ursolic acid, quercetin and lupeol concentrations were quantified by HPLC. Total phenol content and radical scavenging activity of extracts were also measured. The hypocholesterolemic, antioxidant, and hepatoprotective effects of the extracts were examined in hypercholesterolemic rats and compared with orlistat. RESULTS: The highest phenol content, oleanolic acid, quercetin and lupeol levels and free radical scavenging potency were found in the bark extract, and the highest ursolic acid level was found in the berries extract. Orlistat and extracts significantly (P<0.05) lowered the hypercholesterolemia-increased serum level of hepatic enzymes and lipid peroxidation level. Hawthorn's extracts protected from hepatic thiol depletion and improved the lipid profile and hepatic damages. CONCLUSION: Data suggested that hawthorn's extracts are able to protect from hypercholesterolemia-induced oxidative stress and hepatic injuries. Moreover, the hypocholesterolemic effect of extracts was found comparable to orlistat. PMID- 26361539 TI - Characterization of juvenile play in rats: importance of sex of self and sex of partner. AB - BACKGROUND: Juvenile social play is observed in many mammalian species, and its disruption in several neuropsychiatric disorders has greatly increased interest in understanding the origins and sources of variability in this behavior. METHODS: We quantified social play behavior in juvenile rats and investigated the impact of sex and familiarity of the play partner. Sex differences in play behavior were investigated by comparing males and females from either same- or mixed-sex pairs with data pooled over 12 days of analysis. Whether play was altered based on the sex of the play partner was assessed using a paired analysis to compare play with a same- or opposite-sex play partner for both males and females. Additionally, a repeated measures design was utilized to determine whether play changed with increasing age. On postnatal day 33, a novel play partner was introduced. We used a repeated measures analysis to compare postnatal day 33 with the previous day. These approaches were used to assess the effects of age, sex, sex of partner, and familiarity of partner on total social play behavior as well as how play was broken down into components, such as pouncing, pinning, chasing, and boxing. RESULTS: There were sex differences in total frequency of play, and specific parameters of play behavior, such as chasing, pouncing, pinning, and boxing. Additionally, males significantly altered their play behavior in response to the sex of their play partner, whereas females were more sensitive to the familiarity of the play partner. CONCLUSIONS: This study provides critical groundwork for uncovering factors that regulate social play behavior and can be used to guide future mechanistic based work. PMID- 26361540 TI - Development of indicators for measuring outcomes of water safety plans. AB - Water safety plans (WSPs) are endorsed by the World Health Organization as the most effective method of protecting a water supply. With the increase in WSPs worldwide, several valuable resources have been developed to assist practitioners in the implementation of WSPs, yet there is still a need for a practical and standardized method of evaluating WSP effectiveness. In 2012, the Centers for Disease Control and Prevention (CDC) published a conceptual framework for the evaluation of WSPs, presenting four key outcomes of the WSP process: institutional, operational, financial and policy change. In this paper, we seek to operationalize this conceptual framework by providing a set of simple and practical indicators for assessing WSP outcomes. Using CDC's WSP framework as a foundation and incorporating various existing performance monitoring indicators for water utilities, we developed a set of approximately 25 indicators of institutional, operational, financial and policy change within the WSP context. These outcome indicators hold great potential for the continued implementation and expansion of WSPs worldwide. Having a defined framework for evaluating a WSP's effectiveness, along with a set of measurable indicators by which to carry out that evaluation, will help implementers assess key WSP outcomes internally, as well as benchmark their progress against other WSPs in their region and globally. PMID- 26361541 TI - Birth prevalence of selected external structural birth defects at four hospitals in Dar es Salaam, Tanzania, 2011-2012. AB - BACKGROUND: 94% of all birth defects (BD) and 95% of deaths due to the BD occur in low and middle income countries, many of which are preventable. In Tanzania, there is currently a paucity of BD data necessary to develop data informed prevention activities. METHODS: A cross-sectional analysis was conducted of deliveries identified with BD in the labor ward registers at four Dar es Salaam hospitals between October, 2011 and February, 2012. The birth prevalence of structural BD, case fatality proportion, and the distribution of structural defects associated deaths within total deaths were calculated. RESULTS: A total of 28 217 resident births were encountered during the study period. Overall birth prevalence of selected defects was 28.3/10 000 live births. Neural tube defects and indeterminate sex were the most and least common defects at birth (9.9 and 1.1/10 000 live births, respectively). Among stillbirths (66.7%) and deaths that occurred within less than 5 days of an affected live birth (18.5%), neural tube defects were the most frequently associated structural defect. CONCLUSION: Structural BD is common and contributes to perinatal mortality in Dar es Salaam. More than half of perinatal deaths encountered among the studied selected external structural BD are associated with neural tube defects, a birth defect with well-established evidence based prevention interventions. By establishing a population-based BD surveillance program, Tanzania would have the information about neural tube defects and other major structural BD needed to develop and monitor prevention activities. PMID- 26361542 TI - Fatty acids, inflammation and intestinal health in pigs. AB - The intestine is not only critical for nutrient digestion and absorption, but also is the largest immune organ in the body. However, in pig production, inflammation induced by numerous factors, such as pathogen infection and stresses (e.g., weaning), results in intestinal mucosal injury and dysfunction, and consequently results in poor growth of pigs. Dietary fatty acids not only play critical roles in energy homeostasis and cellular membrane composition, but also exert potent effects on intestinal development, immune function, and inflammatory response. Recent studies support potential therapeutic roles for specific fatty acids (short chain and medium chain fatty acids and long chain polyunsaturated fatty acids) in intestinal inflammation of pigs. Results of these new lines of work indicate trophic and cytoprotective effects of fatty acids on intestinal integrity in pigs. In this article, we review the effect of inflammation on intestinal structure and function, and the role of specific fatty acids on intestinal health of pigs, especially under inflammatory conditions. PMID- 26361543 TI - Genetic structure and diversity of the endangered growling grass frog in a rapidly urbanizing region. AB - Two pervasive and fundamental impacts of urbanization are the loss and fragmentation of natural habitats. From a genetic perspective, these impacts manifest as reduced genetic diversity and ultimately reduced genetic viability. The growling grass frog (Litoria raniformis) is listed as vulnerable to extinction in Australia, and endangered in the state of Victoria. Remaining populations of this species in and around the city of Melbourne are threatened by habitat loss, degradation and fragmentation due to urban expansion. We used mitochondrial DNA (mtDNA) and microsatellites to study the genetic structure and diversity of L. raniformis across Melbourne's urban fringe, and also screened four nuclear gene regions (POMC, RAG-1, Rhod and CRYBA1). The mtDNA and nuclear DNA sequences revealed low levels of genetic diversity throughout remnant populations of L. raniformis. However, one of the four regions studied, Cardinia, exhibited relatively high genetic diversity and several unique haplotypes, suggesting this region should be recognized as a separate Management Unit. We discuss the implications of these results for the conservation of L. raniformis in urbanizing landscapes, particularly the potential risks and benefits of translocation, which remains a contentious management approach for this species. PMID- 26361544 TI - Implementing and testing Bayesian and maximum-likelihood supertree methods in phylogenetics. AB - Since their advent, supertrees have been increasingly used in large-scale evolutionary studies requiring a phylogenetic framework and substantial efforts have been devoted to developing a wide variety of supertree methods (SMs). Recent advances in supertree theory have allowed the implementation of maximum likelihood (ML) and Bayesian SMs, based on using an exponential distribution to model incongruence between input trees and the supertree. Such approaches are expected to have advantages over commonly used non-parametric SMs, e.g. matrix representation with parsimony (MRP). We investigated new implementations of ML and Bayesian SMs and compared these with some currently available alternative approaches. Comparisons include hypothetical examples previously used to investigate biases of SMs with respect to input tree shape and size, and empirical studies based either on trees harvested from the literature or on trees inferred from phylogenomic scale data. Our results provide no evidence of size or shape biases and demonstrate that the Bayesian method is a viable alternative to MRP and other non-parametric methods. Computation of input tree likelihoods allows the adoption of standard tests of tree topologies (e.g. the approximately unbiased test). The Bayesian approach is particularly useful in providing support values for supertree clades in the form of posterior probabilities. PMID- 26361545 TI - Modelling human mobility patterns using photographic data shared online. AB - Humans are inherently mobile creatures. The way we move around our environment has consequences for a wide range of problems, including the design of efficient transportation systems and the planning of urban areas. Here, we gather data about the position in space and time of about 16 000 individuals who uploaded geo tagged images from locations within the UK to the Flickr photo-sharing website. Inspired by the theory of Levy flights, which has previously been used to describe the statistical properties of human mobility, we design a machine learning algorithm to infer the probability of finding people in geographical locations and the probability of movement between pairs of locations. Our findings are in general agreement with official figures in the UK and on travel flows between pairs of major cities, suggesting that online data sources may be used to quantify and model large-scale human mobility patterns. PMID- 26361546 TI - Detecting somatic mutations in genomic sequences by means of Kolmogorov-Arnold analysis. AB - The Kolmogorov-Arnold stochasticity parameter technique is applied for the first time to the study of cancer genome sequencing, to reveal mutations. Using data generated by next-generation sequencing technologies, we have analysed the exome sequences of brain tumour patients with matched tumour and normal blood. We show that mutations contained in sequencing data can be revealed using this technique, thus providing a new methodology for determining subsequences of given length containing mutations, i.e. its value differs from those of subsequences without mutations. A potential application for this technique involves simplifying the procedure of finding segments with mutations, speeding up genomic research and accelerating its implementation in clinical diagnostics. Moreover, the prediction of a mutation associated with a family of frequent mutations in numerous types of cancers based purely on the value of the Kolmogorov function indicates that this applied marker may recognize genomic sequences that are in extremely low abundance and can be used in revealing new types of mutations. PMID- 26361547 TI - Iconicity can ground the creation of vocal symbols. AB - Studies of gestural communication systems find that they originate from spontaneously created iconic gestures. Yet, we know little about how people create vocal communication systems, and many have suggested that vocalizations do not afford iconicity beyond trivial instances of onomatopoeia. It is unknown whether people can generate vocal communication systems through a process of iconic creation similar to gestural systems. Here, we examine the creation and development of a rudimentary vocal symbol system in a laboratory setting. Pairs of participants generated novel vocalizations for 18 different meanings in an iterative 'vocal' charades communication game. The communicators quickly converged on stable vocalizations, and naive listeners could correctly infer their meanings in subsequent playback experiments. People's ability to guess the meanings of these novel vocalizations was predicted by how close the vocalization was to an iconic 'meaning template' we derived from the production data. These results strongly suggest that the meaningfulness of these vocalizations derived from iconicity. Our findings illuminate a mechanism by which iconicity can ground the creation of vocal symbols, analogous to the function of iconicity in gestural communication systems. PMID- 26361548 TI - Reproductive success in wild and hatchery male coho salmon. AB - Salmon produced by hatcheries have lower fitness in the wild than naturally produced salmon, but the factors underlying this difference remain an active area of research. We used genetic parentage analysis of alevins produced by experimentally mixed groups of wild and hatchery coho salmon (Oncorhynchus kisutch) to quantify male paternity in spawning hierarchies. We identify factors influencing paternity and revise previously published behavioural estimates of reproductive success for wild and hatchery males. We observed a strong effect of hierarchy size and hierarchy position on paternity: in two-male hierarchies, the first male sired 63% (+/-29%; s.d.) of the alevins and the second male 37% (+/ 29%); in three-male hierarchies, the first male sired 64% (+/-26%), the second male 24% (+/-20%) and the third male 12% (+/-10%). As previously documented, hatchery males hold inferior positions in spawning hierarchies, but we also discovered that hatchery males had only 55-84% the paternity of wild males when occupying the same position within a spawning hierarchy. This paternity difference may result from inferior performance of hatchery males during sperm competition, female mate choice for wild males, or differential offspring survival. Regardless of its cause, the combination of inferior hierarchical position and inferior success at a position resulted in hatchery males having only half (51%) the reproductive success of wild males. PMID- 26361549 TI - A counterview of 'An investigation of the false discovery rate and the misinterpretation of p-values' by Colquhoun (2014). PMID- 26361550 TI - Social dominance modulates eavesdropping in zebrafish. AB - Group living animals may eavesdrop on signalling interactions between conspecifics and integrate it with their own past social experience in order to optimize the use of relevant information from others. However, little is known about this interplay between public (eavesdropped) and private social information. To investigate it, we first manipulated the dominance status of bystander zebrafish. Next, we either allowed or prevented bystanders from observing a fight. Finally, we assessed their behaviour towards the winners and losers of the interaction, using a custom-made video-tracking system and directional analysis. We found that only dominant bystanders who had seen the fight revealed a significant increase in directional focus (a measure of attention) towards the losers of the fights. Furthermore, our results indicate that information about the fighters' acquired status was collected from the signalling interaction itself and not from post-interaction status cues, which implies the existence of individual recognition in zebrafish. Thus, we show for the first time that zebrafish, a highly social model organism, eavesdrop on conspecific agonistic interactions and that this process is modulated by the eavesdroppers' dominance status. We suggest that this type of integration of public and private information may be ubiquitous in social learning processes. PMID- 26361551 TI - Escaping the tragedy of the commons through targeted punishment. AB - Failures of cooperation cause many of society's gravest problems. It is well known that cooperation among many players faced with a social dilemma can be maintained thanks to the possibility of punishment, but achieving the initial state of widespread cooperation is often much more difficult. We show here that there exist strategies of 'targeted punishment' whereby a small number of punishers can shift a population of defectors into a state of global cooperation. We conclude by outlining how the international community could use a strategy of this kind to combat climate change. PMID- 26361552 TI - Object localization using a biosonar beam: how opening your mouth improves localization. AB - Determining the location of a sound source is crucial for survival. Both predators and prey usually produce sound while moving, revealing valuable information about their presence and location. Animals have thus evolved morphological and neural adaptations allowing precise sound localization. Mammals rely on the temporal and amplitude differences between the sound signals arriving at their two ears, as well as on the spectral cues available in the signal arriving at a single ear to localize a sound source. Most mammals rely on passive hearing and are thus limited by the acoustic characteristics of the emitted sound. Echolocating bats emit sound to perceive their environment. They can, therefore, affect the frequency spectrum of the echoes they must localize. The biosonar sound beam of a bat is directional, spreading different frequencies into different directions. Here, we analyse mathematically the spatial information that is provided by the beam and could be used to improve sound localization. We hypothesize how bats could improve sound localization by altering their echolocation signal design or by increasing their mouth gape (the size of the sound emitter) as they, indeed, do in nature. Finally, we also reveal a trade-off according to which increasing the echolocation signal's frequency improves the accuracy of sound localization but might result in undesired large localization errors under low signal-to-noise ratio conditions. PMID- 26361554 TI - Efficient conformational space exploration in ab initio protein folding simulation. AB - Ab initio protein folding simulation largely depends on knowledge-based energy functions that are derived from known protein structures using statistical methods. These knowledge-based energy functions provide us with a good approximation of real protein energetics. However, these energy functions are not very informative for search algorithms and fail to distinguish the types of amino acid interactions that contribute largely to the energy function from those that do not. As a result, search algorithms frequently get trapped into the local minima. On the other hand, the hydrophobic-polar (HP) model considers hydrophobic interactions only. The simplified nature of HP energy function makes it limited only to a low-resolution model. In this paper, we present a strategy to derive a non-uniform scaled version of the real 20*20 pairwise energy function. The non uniform scaling helps tackle the difficulty faced by a real energy function, whereas the integration of 20*20 pairwise information overcomes the limitations faced by the HP energy function. Here, we have applied a derived energy function with a genetic algorithm on discrete lattices. On a standard set of benchmark protein sequences, our approach significantly outperforms the state-of-the-art methods for similar models. Our approach has been able to explore regions of the conformational space which all the previous methods have failed to explore. Effectiveness of the derived energy function is presented by showing qualitative differences and similarities of the sampled structures to the native structures. Number of objective function evaluation in a single run of the algorithm is used as a comparison metric to demonstrate efficiency. PMID- 26361553 TI - Rival assessment among northern elephant seals: evidence of associative learning during male-male contests. AB - Specialized signals emitted by competing males often convey honest information about fighting ability. It is generally believed that receivers use these signals to directly assess their opponents. Here, we demonstrate an alternative communication strategy used by males in a breeding system where the costs of conflict are extreme. We evaluated the acoustic displays of breeding male northern elephant seals (Mirounga angustirostris), and found that social knowledge gained through prior experience with signallers was sufficient to maintain structured dominance relationships. Using sound analysis and playback experiments with both natural and modified signals, we determined that males do not rely on encoded information about size or dominance status, but rather learn to recognize individual acoustic signatures produced by their rivals. Further, we show that behavioural responses to competitors' calls are modulated by relative position in the hierarchy: the highest ranking (alpha) males defend their harems from all opponents, whereas mid-ranking (beta) males respond differentially to familiar challengers based on the outcome of previous competitive interactions. Our findings demonstrate that social knowledge of rivals alone can regulate dominance relationships among competing males within large, spatially dynamic social groups, and illustrate the importance of combining descriptive and experimental methods when deciphering the biological relevance of animal signals. PMID- 26361555 TI - Enabling quaternion derivatives: the generalized HR calculus. AB - Quaternion derivatives exist only for a very restricted class of analytic (regular) functions; however, in many applications, functions of interest are real-valued and hence not analytic, a typical case being the standard real mean square error objective function. The recent HR calculus is a step forward and provides a way to calculate derivatives and gradients of both analytic and non analytic functions of quaternion variables; however, the HR calculus can become cumbersome in complex optimization problems due to the lack of rigorous product and chain rules, a consequence of the non-commutativity of quaternion algebra. To address this issue, we introduce the generalized HR (GHR) derivatives which employ quaternion rotations in a general orthogonal system and provide the left- and right-hand versions of the quaternion derivative of general functions. The GHR calculus also solves the long-standing problems of product and chain rules, mean-value theorem and Taylor's theorem in the quaternion field. At the core of the proposed GHR calculus is quaternion rotation, which makes it possible to extend the principle to other functional calculi in non-commutative settings. Examples in statistical learning theory and adaptive signal processing support the analysis. PMID- 26361556 TI - The advantage of short paper titles. AB - Vast numbers of scientific articles are published each year, some of which attract considerable attention, and some of which go almost unnoticed. Here, we investigate whether any of this variance can be explained by a simple metric of one aspect of the paper's presentation: the length of its title. Our analysis provides evidence that journals which publish papers with shorter titles receive more citations per paper. These results are consistent with the intriguing hypothesis that papers with shorter titles may be easier to understand, and hence attract more citations. PMID- 26361557 TI - Predicting the outcome of competition when fitness inequality is variable. AB - Traditional niche theory predicts that when species compete for one limiting resource in simple ecological settings the more fit competitor should exclude the less fit competitor. Since the advent of neutral theory ecologists have increasingly become interested both in how the magnitude of fitness inequality between competitors and stochasticity may affect this prediction. We used numerical simulations to investigate the outcome of two-species resource competition along gradients of fitness inequality (inequality in R*) and initial population size in the presence of demographic stochasticity. We found that the deterministic prediction of more fit competitors excluding less fit competitors was often unobserved when fitness inequalities were low or stochasticity was strong, and unexpected outcomes such as dominance by the less fit competitor, long-term co-persistence of both competitors or the extinction of both competitors could be common. By examining the interaction between fitness inequality and stochasticity our results mark the range of parameter space in which the predictions of niche theory break down most severely, and suggest that questions about whether competitive dynamics are driven by neutral or niche processes may be locally contingent. PMID- 26361558 TI - Light-emitting diode street lights reduce last-ditch evasive manoeuvres by moths to bat echolocation calls. AB - The light-emitting diode (LED) street light market is expanding globally, and it is important to understand how LED lights affect wildlife populations. We compared evasive flight responses of moths to bat echolocation calls experimentally under LED-lit and -unlit conditions. Significantly, fewer moths performed 'powerdive' flight manoeuvres in response to bat calls (feeding buzz sequences from Nyctalus spp.) under an LED street light than in the dark. LED street lights reduce the anti-predator behaviour of moths, shifting the balance in favour of their predators, aerial hawking bats. PMID- 26361559 TI - An advanced shape-fitting algorithm applied to quadrupedal mammals: improving volumetric mass estimates. AB - Body mass is a fundamental physical property of an individual and has enormous bearing upon ecology and physiology. Generating reliable estimates for body mass is therefore a necessary step in many palaeontological studies. Whilst early reconstructions of mass in extinct species relied upon isolated skeletal elements, volumetric techniques are increasingly applied to fossils when skeletal completeness allows. We apply a new 'alpha shapes' (alpha-shapes) algorithm to volumetric mass estimation in quadrupedal mammals. alpha-shapes are defined by: (i) the underlying skeletal structure to which they are fitted; and (ii) the value alpha, determining the refinement of fit. For a given skeleton, a range of alpha-shapes may be fitted around the individual, spanning from very coarse to very fine. We fit alpha-shapes to three-dimensional models of extant mammals and calculate volumes, which are regressed against mass to generate predictive equations. Our optimal model is characterized by a high correlation coefficient and mean square error (r (2)=0.975, m.s.e.=0.025). When applied to the woolly mammoth (Mammuthus primigenius) and giant ground sloth (Megatherium americanum), we reconstruct masses of 3635 and 3706 kg, respectively. We consider alpha-shapes an improvement upon previous techniques as resulting volumes are less sensitive to uncertainties in skeletal reconstructions, and do not require manual separation of body segments from skeletons. PMID- 26361560 TI - Response to comment by Loiselle & Ramchandra (2015). PMID- 26361561 TI - Magnetic Resonance Elastography for Liver Fibrosis in Methotrexate Treatment. AB - INTRODUCTION: Hepatic magnetic resonance elastography (MRE) allows for noninvasive assessment of liver fibrosis. The purpose of this study was to evaluate the usefulness of MRE in detecting and quantifying liver fibrosis in patients with rheumatoid arthritis (RA) who have received methotrexate (MTX). METHODS: The association between mean liver stiffness value as determined by MRE and variables of interest was determined. The decision for a liver biopsy in participants with an abnormal liver stiffness was made based on clinical judgment. RESULTS: Sixty-five RA patients were enrolled. Mean liver stiffness value by MRE was abnormal in 7 patients, suggestive of hepatic injury. As a result of findings from the MRE, biopsies were performed in 5 patients and all correlated with elevated liver stiffness values. Elevated mean liver stiffness values were associated with body mass index (BMI) (OR= 1.18 per 1 kg/m2; 95% CI: 1.03, 1.36; p=0.017). Neither the total MTX dose nor the duration of MTX treatment was associated with mean liver stiffness value (p=0.51 and P=0.20, respectively). CONCLUSIONS: MRE provides a reliable, non-invasive assessment of liver fibrosis in patients with RA receiving MTX. Patients with RA receiving MTX who have an elevated BMI may be at increased risk for chronic hepatic injury, regardless of MTX cumulative dose or duration of treatment. PMID- 26361562 TI - Pseudoxanthoma elasticum and skin: Clinical manifestations, histopathology, pathomechanism, perspectives of treatment. AB - Pseudoxantoma elasticum (PXE), also known as Groenblad-Strandberg syndrome, is a rare heritable disease with an estimated prevalence of 1:50,000 in the general population. PXE is considered a prototype of multisystem ectopic mineralization disorders and it is characterized by aberrant mineralization of soft connective tissue with degeneration of the elastic fibers, involving primarily the eyes, the cardiovascular system, and the skin. Cutaneous lesions consist of small, asymptomatic, yellowish papules or larger coalescent plaques, typically located on the neck and the flexural areas. PXE is caused by mutations in the ABCC6 (ATP binding cassette subfamily C member 6) gene that encodes a transmembrane ATP binding efflux transporter, normally expressed in the liver and the kidney; however, the exact mechanism of ectopic mineralization remains largely unknown. The histological examination of cutaneous lesions, revealing accumulation of pleomorphic elastic structures in middermis, is essential for the definitive diagnosis of PXE, excluding PXE-like conditions. PXE is currently an intractable disease; although the cutaneous findings primarily present a cosmetic problem, they signify the risk for development of ocular and cardiovascular complications associated with considerable morbidity and mortality. The purpose of this review is to present a comprehensive overview of this rare form of hereditary connective tissue disorders, focus on the pathogenesis, the clinical manifestation, and the differential diagnosis of PXE. Emphasis is also placed on the management of cutaneous lesions and treatment perspectives of PXE. PMID- 26361563 TI - Anxiety disorders in fragile X premutation carriers: Preliminary characterization of probands and non-probands. AB - A very high proportion of individuals with fragile X syndrome (FXS) (FMR1 full mutation, > 200 CGG repeats) experience clinically significant anxiety. Recent evidence suggests that adult fragile X premutation carriers (55-200 CGG repeats) also are at risk for anxiety disorders, and they demonstrate limbic system alterations mediated by FMRP and/or elevated FMR1 mRNA that may explain this heightened risk. However, less is known about psychiatric symptoms including anxiety among children and adolescents with the premutation. We completed structured DSM-IV based diagnostic interviews focused on current anxiety in 35 children, adolescents or young adults with the premutation (ages 5-23 years, M = 11.3 +/- 4.3; 27 male; 20 probands and 15 non-probands) and 31 controls (ages 5 18 years, M = 9.9 +/- 3.6; 22 males). Among premutation carriers, 70.6% met criteria for at least one anxiety disorder (most frequently generalized anxiety disorder, specific phobia, social phobia, or obsessive compulsive disorder), compared to 22.6% of controls and 9.8% of the general population in this age range. Premutation carriers with intellectual disability, male gender, and proband status were associated with the highest rates of anxiety disorders. However, non-probands did have higher rates of having any anxiety disorder (40.0%) compared to general population norms. Although the results implicate anxiety as a target of screening and intervention among youth with the premutation, larger studies of unselected samples from the population of premutation carriers are needed to confirm and specify the degree and extent of psychiatric disorders in this condition. PMID- 26361564 TI - A study of deafness-related genetic mutations as a basis for strategies to prevent hereditary hearing loss in Hebei, China. AB - Hearing loss is the most common sensory disorder, and at least 50% of cases are due to a genetic etiology. Two-thirds of individuals with congenital deafness are nonsyndromic. Among the nonsyndromic forms, the large majority are monogenic autosomal recessive traits. The current work summarizes mutations in the GJB2, SLC26A4, 12SrRNA, and GJB3 and their prevalence in 318 students with autosomal recessive nonsyndromic hearing loss at schools for the deaf or special needs schools in 9 cities in Hebei Province, China. Deafness gene mutations were identified in 137 students via a gene chip, time-of-flight mass spectrometry, fluorescence quantitative PCR, and gene sequencing. Mutations were detected at a rate of 43.08%. A homozygous mutation of the GJB2 gene was found in 16 students (5.03%), a heterozygous mutation of that gene was found in 38 (11.95%), a homozygous mutation of the SLC26A4 gene was found in 22 (6.92%), a heterozygous mutation of that gene was found in 59 (18.55%), and a heterozygous mutation of the mitochondrial 12SrRNA gene was found in 2 (0.63%). In addition, there were 15 families in which a student's parents had normal hearing. Compound heterozygous mutations of the GJB2 gene were found in 3 families (20%) and mutations of the SLC26A4 gene were found in 9 (60%). Thus, this study has provided a molecular diagnostic basis for the causes of deafness, and this study has also provided a scientific basis for the early prevention of and intervention in deafness. PMID- 26361566 TI - Placental site trophoblastic tumor: A case report and literature review. AB - Here, we report a case of a placental site trophoblastic tumor (PSTT) in a 36 year-old Chinese woman 10 months after a normal pregnancy. Two months postpartum, the woman presented with abnormal vaginal discharge and her condition was overlooked by her local hospital. The woman did not receive further attention until a mass with a heterogeneous echo was found in an ultrasound examination eight months postpartum. The final diagnosis was confirmed by histological examinations in conjunction with immunohistochemical studies. Since the patient had potential risk factors, she was successfully treated with a hysterectomy and peri- and post-operative chemotherapy. The latest follow-up (16 months after diagnosis) was uneventful, and the patient exhibited no signs of recurrence or metastasis. PMID- 26361567 TI - Gonadal vein leiomyosarcoma: A case report with radiological findings. AB - A 56 year old postmenopausal lady presented with a rapidly enlarging pelvis mass. Clinical and ultrasonographic features were compatible with a rapidly enlarging fibroid with possible sarcomatous changes, and hence, computated tomography (CT) scan was performed to further delineate the nature and extent of the disease. However, CT scan revealed a huge tumour arising from the retroperitoneal space along the course of the left gonadal vein with typical radiological features of a gonadal vein leiomyosarcoma which were described in previous literatures. With joint collaboration with the surgeons, radical surgery with optimal debulking was subsequently performed for the patient and the diagnosis was confirmed intra operatively and histologically. PMID- 26361568 TI - Inflammatory pseudotumor of the liver: A case report and literature review. AB - Reported here is the case of a 55-year-old man who had tarry stools for 3 days before he was seen at this Department. The man had weight loss and an intermittent fever for 3 months prior. Histopathology revealed an inflammatory pseudotumor of the liver. This case is reported here along with a review of the literature. Nine days after surgery, the patient passed bright red blood (150 mL) in the stool with no clear trigger. A colonoscopy a month later revealed no abnormalities. This is a rare report of an inflammatory pseudotumor featuring intractable bleeding. An inflammatory pseudotumor of the liver is a rare condition, and differentiating this pseudotumor from hepatic space-occupying lesions is crucial. An inflammatory pseudotumor of the liver may spontaneously regress and mimic other liver tumors. The treatment of choice for this pseudotumor is still surgical resection, and this is especially true for patients with severe symptoms or an indeterminate diagnosis. PMID- 26361565 TI - Psychosis and catatonia in fragile X: Case report and literature review. AB - Fragile X mental retardation 1 (FMR1) premutation associated phenotypes have been explored extensively since the molecular mechanism emerged involving elevated FMR1 messenger ribonucleic acid (mRNA) levels. Lowered fragile X mental retardation protein (FMRP) can also occur which may have an additive effect to the high levels of mRNA leading to neurodevelopmental problems and psychopathology. This paper was aimed to review psychosis and catatonia in premutation carriers, express the role of elevated FMR1 mRNA and lowered FMRP in the phenotype of carriers and present a case of psychosis and catatonia in a carrier. This case also demonstrates additional genetic and environmental factors which may also affect the phenotype. We review the literature and report an exemplary case of a 25 year old male premutation carrier with elevated FMR1 mRNA, low FMRP, a cytochrome P450 family 2 subfamily D polypeptide 6 (CYP2D6)*2xN mutation and a perinatal insult. This patient developed an autism spectrum disorder, psychosis, catatonia with subsequent cognitive decline after electro convulsive therapy (ECT) for his catatonia. He had a premutation of 72 CGG repeat in FMR1, FMR1 mRNA level that was over 2.4 times normal and FMRP level at 18% of normal, and additionally, a CYP2D6 allelic variant which leads to ultrarapid metabolism (UM) of medication. There is an overlapping pathophysiological mechanism of catatonia and fragile X-associated premutation phenotypes including autism and psychosis. This case demonstrates the shared phenotype and the overlap of the pathophysiological mechanisms that can influence the intervention. Multiple genetic and environmental hits can lead to more significant involvement in premutation carriers. PMID- 26361569 TI - Ventricular fibrillation development following atrial fibrillation after the ingestion of sildenaphil in a patient with Wolff-Parkinson-White syndrome. AB - Complications in the accessory pathway in Wolff-Parkinson-White (WPW) syndrome could cause different clinical conditions by inducing different arrhythmias. Atrial fibrillation (AF) is one of these arrhythmias and is important as it causes life-threatening arrhythmias. It is known that some drugs, underlying cardiac diseases, and the number of accessory pathways, cause a predisposition to this condition. In the current report, we presented a patient with WPW who was admitted to the emergency department with AF, wide QRS and a rapid ventricular response that progressed to ventricular fibrillation. PMID- 26361570 TI - The Birt-Hogg-Dube cancer predisposition syndrome: Current challenges. AB - Birt-Hogg-Dube is a rare syndrome in which carriers of germline mutations in the FLCN tumor suppressor gene are at risk of renal cell carcinoma of all histologies, most often of the chromophobe or hybrid chromophobe-oncocytoma type. Non-oncological manifestations such as lung cysts, pneumothoraces and skin fibrofolliculomas are also common. How germline mutations in a single gene can cause such different clinical features is intriguing and not fully explained, but involvement of the mTOR (renal cell carcinomas, lung cysts) and WNT (fibrofolliculomas) pathways has been described. Given the rarity of the condition, frequent exchanges of ideas between expert teams from around the world, multicentre international collaborations, and interactions between patients and researchers are essential. These needs are fulfilled through dedicated international symposia held every one to two years and through online resources aimed at patients and relatives. PMID- 26361571 TI - Electrocardiogram in anterior mid-ventricular Takotsubo syndrome variant. PMID- 26361573 TI - Comparison of the trifecta outcomes of robotic and open nephron-sparing surgeries performed in the robotic era of a single institution. AB - PURPOSE: In this study we aimed to report a comparative analysis between open and robotic nephron sparing surgeries (NSS) from a single institutional database. METHODS: Patients who have undergone NSS during the robotic era of our institution were included in this study. Open (n = 74) and robotic (n = 59) groups were compared regarding trifecta outcome. Trifecta was defined as; warm ischemia time (WIT) <25 min, negative surgical margins and the absence of perioperative complications. RESULTS: A total of 57 (77 %) and 45 (76 %) patients in the open and robotic groups, respectively achieved the trifecta outcome. Overall trifecta rate was 77 % (n = 102/133). The only statistically significant difference between trifecta positive and trifecta negative patients was the length of hospitalization (LOH). Except LOH; none of the tested parameters were shown to be predictive of trifecta outcome on univariate and multivariate analyses. Concerning trifecta positive patients; those in the open surgery group had larger tumors with a higher degree of morphometric complexity and were hospitalized for a longer period of time. Additionally, operative duration was significantly higher in the robotic group. CONCLUSIONS: In our cohort, no significant difference in achieving the trifecta outcome was reported after open and robotic NSS. Length of hospitalization was the only parameter that differed significantly between trifecta positive and trifecta negative patients. Surgical approach was not a significant predictor of simultaneous achievement of trifecta outcomes. Irrespective of the trifecta definition; larger and more complicated tumors were handled via open NSS. PMID- 26361574 TI - Quetelet and the emergence of the behavioral sciences. AB - Adolphe Quetelet was one of the most prominent figures of the second half of the nineteenth century, yet in present-day histories of several social sciences the impact of his ideas is widely ignored. The first part consists of a sketch of his life and work. Astronomer and statistician, he sought to apply the mathematical tools of astronomy to create was has been called a 'mathematics of society'. In particular he demonstrated regularities in the incidence of various social phenomena, notably crime, whose implications were widely debated. In the second part the influence he exerted on some key figures in the then emerging social sciences is traced in some detail; these figures include Durkheim, Galton, Marx, and Tylor. He also advocated the wider use of statistics and his call had a powerful impact on the then emerging fields such as administration, economics, sociology and psychology. He influenced some of his most famous contemporaries, including Florence Nightingale, Karl Marx and Francis Galton. PMID- 26361575 TI - Competition for resources: complicated dynamics in the simple Tilman model. AB - Graphical analysis and computer simulations have become the preferred tools to present Tilman's model of resource competition to new generations of ecologists. To really understand the full dynamic behaviour, a more rigorous mathematical analysis is required. We show that just a basic stability analysis is insufficient to describe the relevant dynamics of this deceptively simple model. To investigate realistic invasion and succession processes, not only the stable state is relevant, but also the time scales at which the system moves away from the unstable situation. We argue that the relative stability of saddle points is more important for the actual observed transient dynamics in realistic systems than the predicted asymptotic behaviour towards the stable equilibria. For the mathematical analysis this implies that not only the signs, but also the magnitudes of the eigenvalues of the Jacobi matrix at the stationary points, the rates at which the system evolves, must be considered. We present the underlying mathematics of the Tilman model in a way that should be accessible to any ecologist with a basic mathematical background. PMID- 26361576 TI - Environmental impacts of cage culture in Lake Victoria: the case of Shirati Bay Sota, Tanzania. AB - The experimental cage culture was conducted at Shirati bay, Lake Victoria from February to August 2013, to investigate the impacts of the small scale cage culture on the environment. Three locations along the cages, at the intermediate and one in the offshore (control) were sampled for water quality parameters, phytoplankton and macro invertebrates. A notable increase in nutrient concentration was observed after the set of cages among the stations. However DO, pH, and water transparency showed no major changes and was within the recommended ranges. Cyanophytes an indicator of inorganic pollution dominated before and after the set of cages, an increase in phytoplankton numerical abundance was observed after stocking of fish in cages. In addition there was an increase in the invertebrate community especially bivalves and gastropods. In conclusion we found no consistent environmental change caused by cage culture, and therefore it can be allowed in Lake Victoria, Tanzania part, with close monitoring of its impacts. PMID- 26361577 TI - A rare association of tuberculous longitudinally extensive transverse myelitis (LETM) with brain tuberculoma. AB - BACKGROUND: Longitudinally extensive transverse myelitis is characterized by contiguous inflammatory lesion of spinal cord involving three or more spinal segments. It is a well-recognized but rare presentation of Mycobacterium tuberculosis infection. CASE DESCRIPTION: We report a case of young boy diagnosed with multiple brain tuberculomas. He was on antitubercular drugs therapy for 2 months and became asymptomatic. On 2-month followup visit, the patient complained of acute onset progressive sensorimotor, spastic paraparesis with bladder dysfunction. Magnetic resonance imaging of spine showed longitudinally extensive transverse myelitis extending from thoracic spinal segment T2 to T10 level. He was treated with high dose intravenous methylprednisolone therapy and continued on combination of first line four antitubercular drugs. At 6-month followup, patient was able to walk with support. In our patient, clinical features, previous history of brain tuberculoma and spinal neuroimaging confirmed the diagnosis of tuberculous myelitis. The new onset longitudinally extensive transverse myelitis in our patient was may be related to paradoxical response to antitubercular therapy. CONCLUSIONS: Our case highlights that tubercular infection might be an important but overlooked cause of longitudinally extensive transverse myelitis. Therefore, clinicians should have a high index of suspicion to diagnose this potentially treatable cause especially in high-risk conditions like tuberculosis endemic areas, associated brain tuberculosis and HIV infection. Our case is unique because of paradoxical presentation of longitudinally extensive transverse myelitis in cranial tuberculomas, already on antitubercular treatment. PMID- 26361578 TI - Somatic embryogenesis and plant regeneration of cassava (Manihot esculenta Crantz) landraces from Cameroon. AB - A procedure to regenerate cassava (Manihot esculenta Crantz) cultivars from Cameroon via somatic embryogenesis (SE) was developed. Shoot apical meristems and immature leaf lobes were used as explants on Murashige and Skoog (MS) basal medium containing 33 or 50 uM of the auxins Picloram (Pic), 2,4 Dichlorophenoxyacetic acid (2,4-D), Dicamba (Dic), and alpha-Naphthalene acetic acid. Cultivar performance was assessed using SE and number of somatic embryos produced. Overall, the frequency of primary somatic embryogenesis (PSE) and the mean number of somatic embryos produced varied considerably with genotype, type of auxin and concentration tested. For example, cultivar (cv.) Ngan Mbada showed the best performance on MS medium supplemented with 50 uM Pic with a SE frequency of 40 % and an average number of somatic embryos of 90. The second best performance was recorded in cv. Local Red on MS medium supplemented with 33 uM 2,4-D, where the SE frequency was 40 % and an average number of somatic embryos of 60.5. Cultivar Ekona Red recorded the best performance on medium supplemented with 50 uM Pic showing a SE frequency of 47 % and an average number of somatic embryos of 45. We further examined secondary and cyclic somatic embryogenesis (SSE, CSE) and both were also observed to vary with genotype, however, both exhibited significantly higher frequencies of SE compared with PSE. SE started to decline at the fourth cycle of embryogenesis. Examination of organogenesis showed that shoot bud induction from green cotyledons varied across cultivars and benzylaminopurine was shown to outperform Thidiazuron in the ability to induce organogenesis. Furthermore, the frequencies of bud induction were identical under light and dark conditions. Finally, regenerated plants grew easily in the greenhouse with 90-100 % survival rate and did not display detectable variation in morphology. PMID- 26361579 TI - Seasonal and inter-annual variation in the chlorophyll content of three co existing Sphagnum species exceeds the effect of solar UV reduction in a subarctic peatland. AB - We measured chlorophyll (chl) concentration and chl a/b ratio in Sphagnum balticum, S. jensenii, and S. lindbergii, sampled after 7 and 8 years of ultraviolet-B (UVB) and temperature manipulation in an open field experiment in Finnish Lapland (68 degrees N). We used plastic filters with different transmittance of UVB radiation to manipulate the environmental conditions. The plants were exposed to (1) attenuated UVB and increased temperature, (2) ambient UVB and increased temperature and (3) ambient conditions. Chlorophyll was extracted from the capitula of the mosses and the content and a/b ratio were measured spectrophotometrically. Seasonal variation of chlorophyll concentration in the mosses was species specific. Temperature increase to 0.5-1 degrees C and/or attenuation of solar UVB radiation to ca. one fifth of the ambient (on average 12 vs. 59 uW/cm(2)) had little effect on the chlorophyll concentration or its seasonal variation. In the dominant S. lindbergii, UVB attenuation under increased temperature led to a transient decrease in chlorophyll concentration. Altogether, species-specific patterns of seasonal chlorophyll variation in the studied Sphagna were more pronounced than temperature and UVB treatment effects. PMID- 26361572 TI - Can nanotechnology potentiate photodynamic therapy? AB - Photodynamic therapy (PDT) uses the combination of non-toxic dyes and harmless visible light to produce reactive oxygen species that can kill cancer cells and infectious microorganisms. Due to the tendency of most photosensitizers (PS) to be poorly soluble and to form nonphotoactive aggregates, drug-delivery vehicles have become of high importance. The nanotechnology revolution has provided many examples of nanoscale drug-delivery platforms that have been applied to PDT. These include liposomes, lipoplexes, nanoemulsions, micelles, polymer nanoparticles (degradable and nondegradable), and silica nanoparticles. In some cases (fullerenes and quantum dots), the actual nanoparticle itself is the PS. Targeting ligands such as antibodies and peptides can be used to increase specificity. Gold and silver nanoparticles can provide plasmonic enhancement of PDT. Two-photon excitation or optical upconversion can be used instead of one photon excitation to increase tissue penetration at longer wavelengths. Finally, after sections on in vivo studies and nanotoxicology, we attempt to answer the title question, "can nano-technology potentiate PDT?" PMID- 26361580 TI - Reassessment of carotid intima-media thickness by standard deviation score in children and adolescents after Kawasaki disease. AB - Previous studies that used carotid ultrasound have been largely conflicting in regards to whether or not patients after Kawasaki disease (KD) have a greater carotid intima-media thickness (CIMT) than controls. To test the hypothesis that there are significant differences between the values of CIMT expressed as absolute values and standard deviation scores (SDS) in children and adolescents after KD and controls, we reviewed 12 published articles regarding CIMT on KD patients and controls. The mean +/- SD of absolute CIMT (mm) in the KD patients and controls obtained from each article was transformed to SDS (CIMT-SDS) using age-specific reference values established by Jourdan et al. (J: n = 247) and our own data (N: n = 175), and the results among these 12 articles were compared between the two groups and the references for comparison of racial disparities. There were no significant differences in mean absolute CIMT and mean CIMT-SDS for J between KD patients and controls (0.46 +/- 0.06 mm vs. 0.44 +/- 0.04 mm, p = 0.133, and 1.80 +/- 0.84 vs. 1.25 +/- 0.12, p = 0.159, respectively). However, there were significant differences in mean CIMT-SDS for N between KD patients and controls (0.60 +/- 0.71 vs. 0.01 +/- 0.65, p = 0.042). When we assessed the nine articles on Asian subjects, the difference of CIMT-SDS between the two groups was invariably significant only for N (p = 0.015). Compared with the reference values, CIMT-SDS of controls was within the normal range at a rate of 41.6 % for J and 91.6 % for N. These results indicate that age- and race-specific reference values for CIMT are mandatory for performing accurate assessment of the vascular status in healthy children and adolescents, particularly in those after KD considered at increased long-term cardiovascular risk. PMID- 26361582 TI - Hybrid Bacterial Foraging and Particle Swarm Optimization for detecting Bundle Branch Block. AB - Abnormal cardiac beat identification is a key process in the detection of heart diseases. Our present study describes a procedure for the detection of left and right bundle branch block (LBBB and RBBB) Electrocardiogram (ECG) patterns. The electrical impulses that control the cardiac beat face difficulty in moving inside the heart. This problem is termed as bundle branch block (BBB). BBB makes it harder for the heart to pump blood effectively through the heart circulatory system. ECG feature extraction is a key process in detecting heart ailments. Our present study comes up with a hybrid method combining two heuristic optimization methods: Bacterial Forging Optimization (BFO) and Particle Swarm Optimization (PSO) for the feature selection of ECG signals. One of the major controlling forces of BFO algorithm is the chemotactic movement of a bacterium that models a test solution. The chemotaxis process of the BFO depends on random search directions which may lead to a delay in achieving the global optimum solution. The hybrid technique: Bacterial Forging-Particle Swarm Optimization (BFPSO) incorporates the concepts from BFO and PSO and it creates individuals in a new generation. This BFPSO method performs local search through the chemotactic movement of BFO and the global search over the entire search domain is accomplished by a PSO operator. The BFPSO feature values are given as the input for the Levenberg-Marquardt Neural Network classifier. PMID- 26361581 TI - Complications related to intraoperative transesophageal echocardiography in liver transplantation. AB - PURPOSE: Intraoperative transesophageal echocardiography (TEE) has commonly been used for evaluating cardiac function and monitoring hemodynamic parameters during complex surgical cases. Anesthesiologists may be dissuaded from using TEE in orthotopic liver transplantation (OLT) out of concern about rupture of esophageal varices. Complications associated with TEE in OLT were evaluated. METHODS: We retrospectively reviewed charts and TEE videos of all OLT cases from January 2003 through December 2013 at Mayo Clinic (Jacksonville, Florida). RESULTS: Of the 1811 OLTs performed, we identified 232 patients who underwent intraoperative TEE. Esophageal variceal status was documented during presurgical esophagogastroduodenoscopy in 230 of the 232 patients. Of these, 69 (30.0 %), had no varices; 113 (49.1 %), 41 (17.8 %), and 7 (3.0 %) had grades I, II, and III varices, respectively. Two patients (0.9 %) had no EGD performed because of acute liver failure. During OLT, 1 variceal rupture (0.4 %) occurred after placement of an oral gastric tube and TEE probe; the patient required intraoperative variceal banding. Most patients had preexisting coagulopathy at the time of probe placement. The mean (SD) laboratory test results were as follows: prothrombin time, 21.7 (6.6) seconds; international normalized ratio, 1.9 (1.3); partial thromboplastin time, 43.8 (13.3) seconds; platelet, 93.7 (60.8) * 1000/MUL; and fibrinogen, 237.8 (127.6) mg/dL. CONCLUSION: TEE was a relatively safe procedure with a low incidence of major hemorrhagic complications in patients with documented esophagogastric varices and coagulopathy undergoing OLT. It appeared to effectively disclose cardiac information and allowed rapid reaction for proper patient management. PMID- 26361583 TI - Can titanium mesh influence local recurrence management after implant-based breast reconstruction? AB - INTRODUCTION: TiLOOP((r)) Bra is a permanent titanium-coated polypropylene mesh currently used in post-mastectomy breast reconstruction with implants. This mesh is generally presented as inducing low-grade inflammatory reactions, but only few reports focused on its possible side effects. In the case described here, the use of the mesh led to minor clinical problems that needed to be clinically and surgically managed at the same time as a local relapse. CASE DESCRIPTION: A patient with high-grade ductal carcinoma in situ underwent primary surgery (nipple-sparing mastectomy and one-stage reconstruction using the TiLOOP((r)) Bra mesh) and was subsequently referred for radiological and clinical investigation when various nodules became apparent during a follow-up physical examination. Prior to the histopathological proof, the diagnosis of local recurrence was complicated by the occurrence of an extensive granulomatous reaction in the fixation areas along with mild inflammatory changes scattered on the surface of the mesh. DISCUSSION AND EVALUATION: This case illustrates a side effect of titanium-coated permanent mesh in immediate implant-based reconstruction, i.e. the formation of granulomas in the inframammary fold, probably in the area where the mesh had been folded or fixed. We propose a safer technical approach to avoid the problem and a clinical management strategy for patients at high risk of local recurrence who develop granuloma-like nodules. CONCLUSIONS: A surgical technique is suggested to prevent granuloma formation. If, however, subcutaneous nodules that may be local recurrences do appear, they should not be interpreted by default as a granulomatous reaction, but should be fully investigated and possibly excised. PMID- 26361585 TI - Using Copper to Improve the Well-Being of the Skin. AB - Copper has two key properties that are being exploited in consumer and medical device products in the last decade. On the one hand, copper has potent biocidal properties. On the other hand, copper is involved in numerous physiological and metabolic processes critical for the appropriate functioning of almost all tissues in the human body. In the skin, copper is involved in the synthesis and stabilization of extracellular matrix skin proteins and angiogenesis. This manuscript reviews clinical studies that show that the use of textile consumer and medical device products, embedded with microscopic copper oxide particles, improve the well-being of the skin. These include studies showing a) cure of athlete's foot infections and improvement in skin elasticity, especially important for individuals suffering from diabetes; b) reduction of facial fine line and wrinkles; and c) enhancement of wound healing; by copper oxide embedded socks, pillowcases and wound dressings, respectively. The manuscript also reviews and discusses the mechanisms by which the presence of copper in these products improves skin well-being. PMID- 26361584 TI - Pro-oncogenic cytokines and growth factors are differentially expressed in the post-surgical wound fluid from malignant compared to benign breast lesions. AB - PURPOSE: The accumulation of wound fluid known as seroma in the chest cavity following breast surgery is a common occurrence that can persist for many weeks. While the pro-inflammatory composition of seroma is well established, there has been remarkably little research to determine whether seroma contains pro oncogenic factors, and whether this is influenced by previous malignant disease. METHODS: We developed a clinical trial in which we obtained post-surgical seroma fluids from women with benign or malignant disease 1 or 2 weeks following lumpectomy or mastectomy. We conducted an analysis of more than 80 different cytokines, chemokines and growth factors. RESULTS: We found that surgical cavity seroma from breast cancer patients has a higher expression of key tumor-promoting cytokines and lower expression of important tumor-inhibiting factors when compared to benign lesions from non-cancer patients. Patients with high body mass index also had higher levels of leptin regardless of malignancy. CONCLUSIONS: We conclude that the breast post-surgical tumor cavity contains factors that are pro inflammatory regardless of malignant or benign disease, but in malignant disease there is significant enrichment of additional pro-oncogenic chemokines, cytokines and growth factors, and reduction in tumor-inhibiting factors. These results are consistent with tumor conditioning of surrounding normal stromal tissue and creation of a pro-oncogenic environment that persists long after surgical removal of the tumor. PMID- 26361586 TI - The Effect of Stroke on Pharyngeal Laterality During Swallowing. AB - OBJECTIVE: To investigate whether patterns of dysphagia and swallowing laterality differ according to the location of brain lesions in patients with stroke. METHODS: Patients with stroke >20 years of age were enrolled in this study. A videofluoroscopic swallowing study (VFSS) including the anterior-posterior view was used to assess swallowing. Patterns of swallowing were classified into three types according to the width of barium sulfate flow while passing the pharyngoesophageal segment: right-side-dominant flow, left-side-dominant flow, and no laterality in flow. Laterality was defined when the width of one side was twice or more the width of the other side. RESULTS: A total of 92 patients who underwent swallowing function evaluations by VFSS were enrolled from Sep-tember 2012 to May 2013. Of these, 72 patients had supratentorial lesions (group I) and 20 patients had infratento-rial lesions (group II). Only 10 patients (13.9%) in group I and three patients (15.0%) in group II showed laterality. Of these 13 patients, laterality occurred on the left side regardless of the side of the brain lesion. No relationships were found between swallowing laterality and location of stroke or motor weakness. CONCLUSION: The results suggest that swallowing laterality was not prevalent among patients with stroke and that lesion side, location of the brain lesion, or motor weakness did not influence swallowing laterality. Although stroke can cause symptoms of dysphagia, it is difficult to conclude that stroke has a crucial impact on swallowing laterality. PMID- 26361587 TI - The Effects of the VFSS Timing After Nasogastric Tube Removal on Swallowing Function of the Patients With Dysphagia. AB - OBJECTIVE: To evaluate the effects of the videofluoroscopic swallowing study (VFSS) timing after the nasogastric tube (NGT) removal on swallowing function of the patients with dysphagia. METHODS: This study was conducted on 40 NGT-fed patients with dysphagia. To assess the patients' swallowing function, VFSS was performed twice using a 5-mL 35% diluted barium solution. For the initial examination, VFSS was performed immediately after the NGT removal (VFSS 1). For the second examination, VFSS was performed five hours after the NGT removal (VFSS 2). We used the functional dysphagia scale (FDS) to assess swallowing function. In the FDS, a significant difference in the four items in the oral phase, seven items in the pharyngeal phase, and total scores were assessed (p<0.05). We also used modified penetration-aspiration scale (mPAS) to compare the two examinations (p<0.05). RESULTS: A paired t-test was performed to confirm the statistical significance of the two examinations (p<0.05). The overall swallowing function was assessed as better in VFSS 2 than in VFSS 1. In the FDS, significant differences in the residue in valleculae (p=0.002), the residue in pyriform sinuses (p=0.001), the coating of pharyngeal wall after swallow (p=0.001), and the total scores (p<0.001) were found between the two examinations. Also, in the mPAS that assessed the degree of penetration-aspiration, a significant difference was found between the two examinations (p<0.001). CONCLUSION: The results of this study confirmed that the timing of the VFSS after the NGT removal affects the swallowing function. Thus, to accurately assess the swallowing function, VFSS must be performed in NGT-fed patients after they have rested for a certain period following the removal of their NGT. PMID- 26361588 TI - Effectiveness of Rehabilitative Balloon Swallowing Treatment on Upper Esophageal Sphincter Relaxation and Pharyngeal Motility for Neurogenic Dysphagia. AB - OBJECTIVE: To investigate the relationship between dysphagia severity and opening of the upper esophageal sphincter (UES), and to assess the effect of balloon size on functional improvement after rehabilitative balloon swallowing treatment in patients with severe dysphagia with cricopharyngeus muscle dysfunction (CPD). METHODS: We reviewed videofluoroscopic swallowing studies (VFSS) conducted in the Department of Physical Medicine and Rehabilitation, Myongji Hospital from January through December in 2012. All subjects diagnosed with CPD by VFSS further swallowed a 16-Fr Foley catheter filled with barium sulfate suspension for three to five minutes. We measured the maximum diameter of the balloon that a patient could swallow into the esophagus and subsequently conducted a second VFSS. Then, we applied a statistical technique to correlate the balloon diameter with functional improvement after the balloon treatment. RESULTS: Among 283 inpatients who received VFSS, 21 subjects were diagnosed with CPD. It was observed that the degree of UES opening evaluated by swallowing a catheter balloon had inverse linear correlations with pharyngeal transit time and post-swallow pharyngeal remnant. Videofluoroscopy guided iterative balloon swallowing treatment for three to five minutes, significantly improved the swallowing ability in terms of pharyngeal transit time and pharyngeal remnant (p<0.005 and p<0.001, respectively). Correlation was seen between balloon size and reduction in pharyngeal remnants after balloon treatment (Pearson correlation coefficient R= 0.729, p<0.001), whereas there was no definite relationship between balloon size and improvement in pharyngeal transit time (R=-0.078, p=0.738). CONCLUSION: The maximum size of the balloon that a patient with CPD can swallow possibly indicates the maximum UES opening. The iterative balloon swallowing treatment is safe without the risk of aspiration, and it can be an effective technique to improve both pharyngeal motility and UES relaxation. PMID- 26361589 TI - Different Movement of Hyolaryngeal Structures by Various Application of Electrical Stimulation in Normal Individuals. AB - OBJECTIVE: To identify the differences in the movement of the hyoid bone and the vocal cord with and without electrical stimulation in normal subjects. METHODS: Two-dimensional motion analysis using a videofluoroscopic swallowing study with and without electrical stimulation was performed. Surface electrical stimulation was applied during swallowing using electrodes placed at three different locations on each subject. All subjects were analyzed three times using the following electrode placements: with one pair of electrodes on the suprahyoid muscles and a second pair on the infrahyoid muscles (SI); with placement of the electrode pairs on only the infrahyoid muscles (IO); and with the electrode pairs placed vertically on the suprahyoid and infrahyoid muscles (SIV). RESULTS: The main outcomes of this study demonstrated an initial downward displacement as well as different movements of the hyoid bone with the three electrode placements used for electrical stimulation. The initial positions of the hyoid bone with the SI and IO placements resulted in an inferior and anterior displaced position. During swallowing, the hyoid bone moved in a more superior and less anterior direction, resulting in almost the same peak position compared with no electrical stimulation. CONCLUSION: These results demonstrate that electrical stimulation caused an initial depression of the hyoid bone, which had nearly the same peak position during swallowing. Electrical stimulation during swallowing was not dependent on the position of the electrode on the neck, such as on the infrahyoid or on both the suprahyoid and infrahyoid muscles. PMID- 26361590 TI - The Relationship Between Sleep Disturbance and Functional Status in Mild Stroke Patients. AB - OBJECTIVE: To investigate the sleep state of mild stroke patients and relationship between sleep disturbance and functional status. METHODS: A total of 80 acute stroke patients were enrolled in this study. The criteria for inclusion in the study was as following: 1) first stroke, 2) cognitive function preserved enough to perform the test (Mini Mental State Examination >=24), 3) good functional levels (Modified Rankin Scale <=3), 4) upper extremity motor function preserved enough to perform occupational tests (hand strength test, Purdue pegboard test, 9-hole peg test, and Medical Research Council score >=3), and 5) less than 2 weeks between the stroke and the assessment. Quality of sleep was assessed by using Pittsburg Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Insomnia Severity Index (ISI), and Stanford Sleepiness Scale (SSS). Activities of daily living was assessed by using the Modified Barthel Index (MBI) and depressed mood was assessed by using the Beck Depression Inventory (BDI). Gross and fine motor function of the upper extremity was assessed by using hand strength test (Jamar dynamometer), Purdue pegboard test, and the 9-hole peg test. RESULTS: The results of the occupational assessment were fine in the good sleepers. The PSQI, ESS, and ISI were correlated with some of the assessment tools (BDI, MBI, Purdue pegboard, 9-hole peg, and hand strength). CONCLUSION: In conclusion, this study emphasizes that sleep disturbance can affect the functional status in mild acute stroke patients. Therefore, clinicians must consider sleep status in stroke patients and need to work to control it. PMID- 26361591 TI - Predictability of Motor Outcome According to the Time of Motor Evoked Potentials From the Onset of Stroke in Patients With Putaminal Hemorrhage. AB - OBJECTIVE: To determine the predictability of motor evoked potentials (MEP) in patients with putaminal hemorrhage (PH) according to the time of MEP from the onset of stroke. METHODS: Sixty consecutive patients with PH from January 2006 to November 2013 were retrospectively reviewed. Motor function of affected extremities was measured at onset time and at six months after the onset. Patients were classified into two groups according to the time of MEP from the onset of stroke: early MEP group (within 15 days from onset) and late MEP group (16-30 days from onset). Patients were also classified into two groups according to the presence of MEP on the affected abductor pollicis brevis (APB): MEP (+) group-patients (showing MEP in the affected APB) and MEP (-) group-patients (no MEP in the affected APB). Motor outcome was compared between the two early and late MEP groups or between the presence and absence of MEP in the affected APB groups. RESULTS: For patients with MEP (+), a larger portion in the late MEP group showed good prognosis compared to the early MEP group (late MEP, 94.4%; early MEP, 80%). In contrast, in patients with MEP (-), a larger portion of patients in the late MEP group showed bad prognosis compared to the early MEP group (late MEP, 80%; early MEP, 71.4%). No significant improvement of MI between MEP (+) and MEP (-) was observed when MEP was performed early or late. CONCLUSION: Our results revealed that the predictability of motor outcome might be better if MEP is performed late compared to that when MEP is performed early in patients with PH. PMID- 26361592 TI - Functional Improvement After 4-Week Rehabilitation Therapy and Effects of Attention Deficit in Brain Tumor Patients: Comparison With Subacute Stroke Patients. AB - OBJECTIVE: To confirm functional improvement in brain tumor patients after 4-week conventional rehabilitation therapy, to compare the cognitive impairment of brain tumor patients with subacute stroke patients using computerized neuropsychological testing, and to determine the effects on functional outcomes of daily activity. METHODS: From April 2008 to December 2012, 55 patients (29 brain tumor patients and 26 subacute stroke patients) were enrolled. All patients were assessed with a computerized neuropsychological test at baseline. Motricity Index, Korean version of Mini Mental Status Examination, and Korean version of Modified Barthel Index scores were assessed at the beginning and end of 4-week rehabilitation. Conventional rehabilitation therapy was applied to both groups for 4 weeks. RESULTS: Functional outcomes of all patients in both groups significantly improved after 4-week rehabilitation therapy. In brain tumor patients, the initial Motricity Index, cognitive dysfunction, and visual continuous performance test correction numbers were strong predictors of initial daily activity function (R(2)=0.778, p<0.01). The final Motricity Index and word black test were strong predictors of final daily activity function (R(2)=0.630, p<0.01). In patients with subacute stroke, the initial Motricity index was an independent predictor of initial daily activity function (R(2)=0.245, p=0.007). The initial daily activity function and color of color word test were strong predictors of final daily activity function (R(2)=0.745, p<0.01). CONCLUSION: Conventional rehabilitation therapy induced functional improvement in brain tumor patients. Objective evaluation of cognitive function and comprehensive rehabilitation including focused cognitive training should be performed in brain tumor patients for improving their daily activity function. PMID- 26361593 TI - Prediction of Motor Recovery Using Diffusion Tensor Tractography in Supratentorial Stroke Patients With Severe Motor Involvement. AB - OBJECTIVE: To investigate whether early stage diffusion tensor tractography (DTT) values predict motor function at 3 months after onset in supratentorial stroke patients with severe motor involvement. METHODS: A retrospective study design was used to analyze medical records and neuroimaging data of 49 supratentorial stroke patients with severe motor involvement. Diffusion tensor imaging was assessed within 3 weeks after stroke in all patients. Three-dimensional tractography of the ipsilateral corticospinal tract (CST) was performed using the fiber assignment of the continuous tracking algorithm. The two-step DTT analysis was used. The first step was classification according to ipsilateral CST visualization. The second step was a quantitative analysis of the visible-CST group parameters. Motor function was assessed at 2 weeks and at 3 months after stroke. Comparative and correlation analyses were performed between DTT-derived measures and motor assessment scores. RESULTS: Motor function of the upper extremity at 3 months after stroke was significantly higher in the visible-CST group than that in the nonvisible-CST group (p<0.05). Early stage fractional anisotropy was of DTT correlated significantly with upper extremity motor function at 3 months after stroke in the visible-CST group (p<0.05). CONCLUSION: These results demonstrate that early DTT-derived measures predict motor recovery in the upper extremity at 3 months after onset in supratentorial stroke patients with severe motor involvement. PMID- 26361594 TI - Hemiparetic Knee Extensor Strength and Balance Function Are Predictors of Ambulatory Function in Subacute Stroke Patients. AB - OBJECTIVE: To identify the potential predictors of ambulatory function in subacute stroke patients, and to determine the contributing factors according to gait severity. METHODS: Fifty-three subacute stroke patents were enrolled. Ambulatory function was assessed by gait speed and endurance. Balance function was evaluated by the Berg Balance Scale score (BBS) and the Timed Up and Go test (TUG). The isometric muscular strengths of bilateral knee extensors and flexors were measured using an isokinetic dynamometer. Cardiovascular fitness was evaluated using an expired gas analyzer. Participants were assigned into the household ambulator group (<0.4 m/s) or the community ambulator group (>=0.4 m/s) based on gait severity. RESULTS: In the linear regression analyses of all patients, paretic knee isometric extensor strength (p=0.007) and BBS (p<0.001) were independent predictors of gait endurance (R(2)=0.668). TUG (p<0.001) and BBS (p=0.037) were independent predictors of gait speed (R(2)=0.671). Paretic isometric extensor strength was a predictor of gait endurance (R(2)=0.340, p=0.008). TUG was a predictor of gait speed (R(2)=0.404, p<0.001) in the household ambulator group, whereas BBS was a predictive factor of gait endurance (R(2)=0.598, p=0.008) and speed (R(2)=0.713, p=0.006). TUG was a predictor of gait speed (R(2)=0.713, p=0.004) in the community ambulator group. CONCLUSION: Our results reveal that balance function and knee extensor isometric strength were strong predictors of ambulatory function in subacute stroke patients. However, they work differently according to gait severity. Therefore, a comprehensive functional assessment and a different therapeutic approach should be provided depending on gait severity in subacute stroke patients. PMID- 26361595 TI - Handwriting Rehabilitation in Parkinson Disease: A Pilot Study. AB - OBJECTIVE: To assess the utility of handwriting rehabilitation (HR) in Parkinson disease (PD) patients who experienced difficulties with handwriting and signing. METHODS: Sixty PD patients were prospectively studied with graphological evaluations. Thirty PD patients were assigned to HR for 9 weeks. At the end of this training, all patients were evaluated again and results of basal vs. final evaluations were compared. RESULTS: At final evaluation, the group assigned to HR showed significantly larger amplitude of the first 'e' in the phrase, larger signature surface area, and superior margin. A trend of increase in letter size was also observed. Handwriting with progressively decreasing size of letters and ascending direction with respect to the horizontal were prominent findings in both groups of patients and they did not change after HR. CONCLUSION: Rehabilitation programs for handwriting problems in PD patients are likely to be helpful. Larger randomized studies are needed to confirm these results. PMID- 26361596 TI - Effects of Indoor Rowing Exercise on the Body Composition and the Scoliosis of Visually Impaired People: A Preliminary Study. AB - OBJECTIVE: To evaluate the effects of rowing exercise on body composition, laboratory data, fitness and scoliosis in visually impaired people. The majority of visually impaired people do not participate in active sports due to efficiency and safety issues. Rowing is a safe whole-body exercise with aerobic and anaerobic components. METHODS: Twenty subjects were recruited from among those admitted to a facility for visually impaired people (16 men and 4 women). Laboratory data, body composition, physical fitness, Cobb's angle, and fall index were checked before and after 6 weeks (5 days a week) of indoor rowing using Concept2 Model E. RESULTS: After the training, fat mass and total body fat percent decreased significantly. In the fitness test, back strength and trunk flexion score increased significantly. Laboratory data showed significant increases in serum protein and albumin and decreases in low-density lipoprotein (LDL) cholesterol. There were 9 subjects with scoliosis and after the training Cobb's angle decreased by 1.11 degrees +/-1.55 degrees , though this was not statistically significant. CONCLUSION: Visually impaired people frequently have abnormal body composition, low physical fitness, and scoliosis. A rowing exercise program can be helpful, with a positive effect on body composition and physical fitness; however, with respect to scoliosis, we need an earlier intervention program in visually impaired people. PMID- 26361597 TI - Mobile Sensor Application for Kinematic Detection of the Knees. AB - OBJECTIVE: To correctly measure the knee joint angle, this study utilized a Qualisys motion capture system and also used it as the reference to assess the validity of the study's Inertial Measurement Unit (IMU) system that consisted of four IMU sensors and the Knee Angle Recorder software. The validity was evaluated by the root mean square (RMS) of different angles and the intraclass correlation coefficient (ICC) values between the Qualisys system and the IMU system. METHODS: Four functional knee movement tests for ten healthy participants were investigated, which were the knee flexion test, the hip and knee flexion test, the forward step test and the leg abduction test, and the walking test. RESULTS: The outcomes of the knee flexion test, the hip and knee flexion test, the forward step test, and the walking test showed that the RMS of different angles were less than 6 degrees . The ICC values were in the range of 0.84 to 0.99. However, the leg abduction test showed a poor correlation in the measurement of the knee abduction-adduction movement. CONCLUSION: The IMU system used in this study is a new good method to measure the knee flexion-extension movement. PMID- 26361598 TI - A Survey of the Status of Awareness of Lymphedema in Breast Cancer Patients in Busan-Gyeongnam, Korea. AB - OBJECTIVE: To support the establishment of lymphedema education plans and the actual practice of education by investigating the current lymphedema awareness status of Korean breast cancer patients. METHODS: cross-sectional population survey was conducted in 116 breast cancer patients in the Busan-Gyeongnam area. The survey included questions regarding demographic characteristics, breast cancer-related lymphedema (BCRL) risk factors, and characteristics and treatments of the disease. Some of the items were scored to determine the level of awareness. The items that affect the awareness of lymphedema were investigated by statistical analysis. RESULTS: Eighty-one of the 116 patients answered that they had heard of lymphedema, and 30 of them (25.86%) had received explanations about the possibility of lymphedema before surgery. Only 20 patients (17.25%) knew that lymphedema is not a completely curable disease, 24 patients (20.68%) thought that lymphedema does not require any treatment, and only 56 patients (48.27%) knew that lymphedema is treated in the Department of Rehabilitation Medicine. The main factors that affected patients' awareness of lymphedema were their age, chemotherapy, duration of breast cancer, and lymphedema treatment history. CONCLUSION: The majority of survey participants who were breast cancer patients either lacked awareness of BCRL or had false ideas about it, indicating the inadequate level of education provided for lymphedema. In the case of breast cancer diagnosis, early and continuous education for future management is essential, and the framework for the provision of education including education protocols related to age, disease duration, and lymphedema treatment is needed. PMID- 26361599 TI - The Dose-Related Effects of Extracorporeal Shock Wave Therapy for Knee Osteoarthritis. AB - OBJECTIVE: To investigate the dose-related effects of extracorporeal shock wave therapy (ESWT) for knee osteoarthritis. METHODS: Seventy-five subjects were recruited, 60 of which met the inclusion criteria. The patients were randomly classified into two groups: group L, which was a low-energy group (n=30; 1,000 shocks/session; energy flux density [EFD], 0.040 mJ/mm(2)) and group M, which was a medium-energy group (n=30; 1,000 shocks/session; EFD, 0.093 mJ/mm(2)). For each group, 1,000 shock waves were delivered to the medial tibial plateau area, once a week, for 3 weeks. The main outcome measures were the visual analogue scale (VAS), the Roles and Maudsley (RM) score, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, and the Lequesne index. Each assessment was performed at the baseline and at 1, 4, and 12 weeks after ESWT. RESULTS: In both groups, the VAS, the RM and WOMAC scores, and the Lequesne index were significantly improved over time (p<0.001), and group M showed greater improvement over group L at the 1, 4 and 12 weeks assessments. CONCLUSION: In this study, medium-energy group (group M) showed greater improvement in regard to relieving pain and restoring functional outcome than the low-energy group (group L). Therefore, EFD can be considered to have significant influence when treating with ESWT for knee osteoarthritis. PMID- 26361600 TI - Gross Motor Function Outcome After Intensive Rehabilitation in Children With Bilateral Spastic Cerebral Palsy. AB - OBJECTIVE: To compare gross motor function outcomes in children with moderate to severe degrees of bilateral spastic cerebral palsy (CP) who received either intensive inpatient rehabilitation or intermittent rehabilitation on an outpatient basis. METHODS: A non-biased retrospective chart review was done for patients diagnosed with bilateral spastic CP who received rehabilitation therapy. The intensive rehabilitation group (inpatient group) agreed to be hospitalized to receive 22 sessions of physical and occupational therapy per week for 1 month. The intermittent rehabilitation group (outpatient group) received four sessions of physical and occupational therapy per week for 3 months in an outpatient setting. Changes in the total score on the Gross Motor Function Measure (GMFM) between baseline and the follow-up period were analyzed. RESULTS: Both groups showed significant improvements in total GMFM scores at the follow-up assessment compared to that at baseline (p=0.000 for inpatient group, p=0.001 for outpatient group). The increase in mean total GMFM score after 1 month was significantly greater in the inpatient group than that in the outpatient group (p=0.020). Higher increase in GMFM score was observed in younger subjects as revealed by the negative correlation between age and the increase in GMFM score after 1 month (p=0.002, r=-0.460). CONCLUSION: Intensive inpatient rehabilitation therapy for patients with bilateral spastic CP of moderate to severe degree was more effective for improving gross motor function than intermittent rehabilitation therapy on an outpatient basis. PMID- 26361601 TI - Successful Treatment of Phantom Limb Pain by 1 Hz Repetitive Transcranial Magnetic Stimulation Over Affected Supplementary Motor Complex: A Case Report. AB - A 37-year-old man with a right transfemoral amputation suffered from severe phantom limb pain (PLP). After targeting the affected supplementary motor complex (SMC) or primary motor cortex (PMC) using a neuro-navigation system with 800 stimuli of 1 Hz repetitive transcranial magnetic stimulation (rTMS) at 85% of resting motor threshold, the 1 Hz rTMS over SMC dramatically reduced his visual analog scale (VAS) of PLP from 7 to 0. However, the 1 Hz rTMS over PMC failed to reduce pain. To our knowledge, this is the first case report of a successfully treated severe PLP with a low frequency rTMS over SMC in affected hemisphere. PMID- 26361602 TI - A Long-Term Follow-up of Pontine Hemorrhage With Hearing Loss. AB - A pontine intracranial hemorrhage (ICH) evokes several neurological symptoms, due to the various nuclei and nerve fibers; however, hearing loss from a pontine ICH is rare. We have experienced a non-traumatic pontine ICH patient, with hearing loss. A 43-year-old male patient had a massive pontine hemorrhage; his brain magnetic resonance imaging revealed the hemorrhage on the bilateral dorsal pons, with the involvement of the trapezoid body. Also, profound hearing loss on the pure-tone audiogram and abnormal brainstem auditory evoked potential were noticed. Fifty-two months of long-term follow-up did not reveal any definite improvement on the patient's hearing ability. PMID- 26361603 TI - Terson Syndrome in Aneurysmal Subarachnoid Hemorrhage: A Case Report. AB - Terson syndrome refers to oculocerebral syndrome of retinal and vitreous hemorrhage associated with spontaneous subarachnoid hemorrhage or all forms of intracranial bleeding. Recent observations have indicated that patients with spontaneous subarachnoid hemorrhage have an 18% to 20% concurrent incidence of retinal and vitreous hemorrhages with about 4% incidence of vitreous hemorrhage alone. Clinical ophthalmologic findings may have significant diagnostic and prognostic value for clinicians. Here we report a 45-year-old female patient who suffered from blurred vision after subarachnoid hemorrhage. She was diagnosed as Terson syndrome. After vitrectomy, she recovered with normal visual acuity which facilitated the rehabilitative process. We also performed visual evoked potentials to investigate abnormalities of visual dysfunction. Based on this case, we emphasize the importance of early diagnosis of Terson syndrome. PMID- 26361604 TI - Myotonic Dystrophy Type 1 Complicated With Peripheral Arterial Occlusive Disease: A Case Report. AB - Myotonic dystrophy (MD) is the most common adult muscular dystrophy characterized by multi-systemic clinical manifestations involving the brain, smooth muscle, cardiovascular and endocrine systems. However, peripheral arterial occlusive disease (PAOD) is an uncommon presentation of MD type 1 (DM1), which has not been reported in recent literature. A 53-year-old female, previously confirmed as DM1, presented with vague claudication of both lower limbs. The diagnosis of PAOD based on results of ankle-brachial index, ultrasonography, and abdominal computed tomography angiography studies was followed by aortobifemoral artery bypass surgery. Although the arterial patency was restored after the operation, she did not recover from post-operative respiratory complications. Screening of PAOD is necessary for DM1 with general risk factors of occlusive arteriopathy. However, surgery should be reserved for the most severe cases. PMID- 26361605 TI - Lumbar Epidural Steroid Injection for Painful Spasticity in Cervical Spinal Cord Injury: A Case Report. AB - We report a case of a 53-year-old male with traumatic cervical spinal cord injury (SCI). He could not maintain a standing position because of painful spasticity in his lower limbs. A magnetic resonance imaging and electromyography indicated chronic lumbosacral radiculopathy, explaining his chronic low back pain before the injury. For diagnostic as well as therapeutic purposes, transforaminal epidural steroid injection (ESI) to the right L5 root was performed. After the intervention, the spasticity decreased and his ambulatory function improved. This case illustrates that lumbar radiculopathy concomitant with a cervical SCI can produce severe spasticity and it can be dramatically improved by ESI. PMID- 26361607 TI - Correction: Neuroradiological and Neurophysiological Characteristics of Patients With Dyskinetic Cerebral Palsy. AB - [This corrects the article on p. 189 in vol. 38, PMID: 24855613.]. PMID- 26361606 TI - A Patient With Focal Dystonia That Occurred Secondary to a Peripheral Neurogenic Tumor: A Case Report. AB - Dystonia is a movement disorder characterized by involuntary muscle contractions. Patients with dystonia may experience uncontrollable twisting, repetitive movements, or abnormal posture. A 55-year-old man presented with an involuntary left forearm supination, which he had experienced for five years. There was no history of antecedent trauma to the wrist or elbow. Although conventional therapeutic modalities had been performed, the symptoms persisted. When he visited our hospital, electromyography was performed. Reduced conduction velocity was evident at the elbow-axilla segment of the left median nerve. We suspected that there was a problem on the median nerve between the elbow and the axilla. For this reason, we performed an ultrasonography and magnetic resonance imaging study. A spindle-shaped soft tissue mass was observed at the left median nerve that suggested the possibility of neurofibroma. Dystonia caused by traumatic or compressive peripheral nerve injury has often been reported, but focal dystonia due to a neurogenic tumor is extremely rare. Here, we report our case with a review of the literature. PMID- 26361608 TI - Safe usage of cosmetics in Bangladesh: a quality perspective based on microbiological attributes. AB - The present review attempted to emphasize on the microbiological quality of the commonly used cosmetics item by the majority of the Bangladeshi community. The abundance of contaminating microorganisms has been quantitatively discussed and the possible health risk has been focused upon usage of these items. Only a very few research efforts have been conducted on the cosmetic items in Bangladesh so far. The microbiological contamination aspects have been portrayed in this review using the information collected from a substantial number of cosmetic items which were earlier subjected to extensive microbiological and biochemical analyses. The prevalence of bacteria, fungi and the specific pathogenic microorganisms has been discussed based on research so far locally conducted on the finished items sold in markets, especially within the Dhaka metropolis. The laboratory scale experiments revealed the presence of enormous number of bacteria, actinomycetes and fungi within the commonly used cosmetics. Conversely, the anti-bacterial activity was noticed in some of the products which might be in favor of the user safety. The prevalence of pathogenic microorganisms in the cosmetic items certainly raises a substantial public health issue. The necessity of the routine microbiological testing of the commonly used cosmetic items as well as the legislative measures to mitigate the contamination problem is thus of great significance. PMID- 26361609 TI - Is Low-Dose-Rate Endorectal Brachytherapy a New Treatment Method for Locally Advanced Distal Rectal Cancer? PMID- 26361610 TI - Should a Contrast Enema Be Performed Before Reversal of a Diverting Stoma in Lower Rectal Surgery? PMID- 26361611 TI - Biofeedback Therapy After Sphincter-Preservation Surgery for the Treatment of Rectal Cancer. PMID- 26361612 TI - Anti-tumor Necrosis Factor Therapy for Crohn Disease: Friend or Foe to the Surgeon? PMID- 26361613 TI - Efficacy and Safety of Low-Dose-Rate Endorectal Brachytherapy as a Boost to Neoadjuvant Chemoradiation in the Treatment of Locally Advanced Distal Rectal Cancer: A Phase-II Clinical Trial. AB - PURPOSE: Despite advances in rectal cancer treatment over the last decade, local control and risk of late side effects due to external beam radiation therapy (EBRT) remain as concerns. The present study aimed to investigate the efficacy and the safety of low-dose-rate endorectal brachytherapy (LDRBT) as a boost to neoadjuvant chemoradiation for use in treating locally advanced distal rectal adenocarcinomas. METHODS: This phase-II clinical trial included 34 patients (as the study arm) with newly diagnosed, locally advanced (clinical T3-T4 and/or N1/N2, M0) lower rectal cancer. For comparative analysis, 102 matched patients (as the historical control arm) with rectal cancer were also selected. All the patients were treated with LDRBT (15 Gy in 3 fractions) and concurrent chemoradiation (45-50.4 Gy). Concurrent chemotherapy consisted of oxaliplatin 130 mg/m(2) intravenously on day 1 plus oral capecitabine 825 mg/m(2) twice daily during LDRBT and EBRT. RESULTS: The study results revealed a significant differences between the study arm and the control arm in terms in the pathologic tumor size (2.1 cm vs. 3.6 cm, P = 0.001), the pathologic tumor stage (35% T3-4 vs. 65% T3-4, P = 0.003), and the pathologic complete response (29.4% vs. 11.7%, P < 0.028). Moreover, a significantly higher dose of EBRT (P = 0.041) was found in the control arm, and a longer time to surgery was observed in the study arm (P < 0.001). The higher rate of treatment-related toxicities, such as mild proctitis and anemia, in the study arm was tolerable and easily manageable. CONCLUSION: A boost of LDRBT can optimize the pathologic complete response, with acceptable toxicities, in patients with distal rectal cancer. PMID- 26361614 TI - Assessment by Using a Water-Soluble Contrast Enema Study of Radiologic Leakage in Lower Rectal Cancer Patients With Sphincter-Saving Surgery. AB - PURPOSE: This study evaluated the efficacy of a water-soluble contrast enema (WCE) in predicting anastomotic healing after a low anterior resection (LAR). METHODS: Between January 2000 and March 2012, 682 consecutive patients underwent a LAR or an ultra-low anterior resection (uLAR) and were followed up for leakage. Clinical leakage was established by using physical and laboratory findings. Radiologic leakage was identified by using retrograde WCE imaging. Abnormal radiologic features on WCE were categorized into four types based on morphology: namely, dendritic, horny, saccular, and serpentine. RESULTS: Of the 126 patients who received a concurrent diverting stoma, only two (1.6%) suffered clinical leakage due to pelvic abscess. However, 37 patients (6.7%) in the other group suffered clinical leakage following fecal diversion (P = 0.027). Among the 163 patients who received a fecal diversion, 20 showed radiologic leakage on the first WCE (eight with and 12 without a concurrent diversion); 16 had abnormal features continuously until the final WCE while four patients healed spontaneously. Eleven of the 16 patients (69%), by their surgeon's decision, underwent a stoma restoration based on clinical findings (2/3 dendritic, 3/4 horny, 5/7 saccular, 1/2 serpentine). After stoma reversal, only 2 of the 11 (19%) complained of complications related to the rectal anastomosis. CONCLUSION: WCE is helpful for detecting radiologic leakage before stoma restoration, especially in patients suffering clinical leakage after an uLAR. However, surgeons appear to opt for stoma restoration despite the persistent existence of radiologic leakage in cases with particular features on the WCE. PMID- 26361615 TI - Biofeedback Therapy Before Ileostomy Closure in Patients Undergoing Sphincter Saving Surgery for Rectal Cancer: A Pilot Study. AB - PURPOSE: This study prospectively investigated the effects of biofeedback therapy on objective anorectal function and subjective bowel function in patients after sphincter-saving surgery for rectal cancer. METHODS: Sixteen patients who underwent an ileostomy were randomized into two groups, one receiving conservative management with the Kegel maneuver and the other receiving active biofeedback before ileostomy closure. Among them, 12 patients (mean age, 57.5 years; range, 38 to 69 years; 6 patients in each group) completed the study. Conservative management included lifestyle modifications, Kegel exercises, and medication. Patients were evaluated at baseline and at 1, 3, 6, and 12 months after ileostomy closure by using anal manometry, modified Wexner Incontinence Scores (WISs), and fecal incontinence quality of life (FI-QoL) scores. RESULTS: Before the ileostomy closure, the groups did not differ in baseline clinical characteristics or resting manometric parameters. After 12 months of follow-up, the biofeedback group demonstrated a statistically significant improvement in the mean maximum squeezing pressure (from 146.3 to 178.9, P = 0.002). However, no beneficial effect on the WIS was noted for biofeedback compared to conservative management alone. Overall, the FI-QoL scores were increased significantly in both groups after ileostomy closure (P = 0.006), but did not differ significantly between the two groups. CONCLUSION: Although the biofeedback therapy group demonstrated a statistically significant improvement in the maximum squeezing pressure, significant improvements in the WISs and the FI-QoL scores over time were noted in both groups. The study was terminated early because no therapeutic benefit of biofeedback had been demonstrated. PMID- 26361616 TI - Long-term Outcomes and Risk Factors for Reoperation After Surgical Treatment for Gastrointestinal Crohn Disease According to Anti-tumor Necrosis Factor-alpha Antibody Use: 35 Years of Experience at a Single Institute in Korea. AB - PURPOSE: Crohn disease is characterized by high rates of recurrence and reoperations. However, few studies have investigated long-term surgical outcomes in Asian populations. We investigated risk factors for reoperation, particularly those associated with anti-tumor necrosis factor-alpha (anti-TNF-alpha) antibody use, and long-term follow-up results. METHODS: We reviewed the records of 148 patients (100 males and 48 females) who underwent surgery for gastrointestinal Crohn disease and retrospectively analyzed long-term outcomes and risk factors. RESULTS: The mean age at diagnosis was 28.8 years. Thirty-eight patients (25.7%) received monoclonal antibody treatment before reoperation. A small bowel and colon resection was most commonly performed (83 patients, 56.1%). The median follow-up was 149 months, during which 47 patients underwent reoperation. The median interval between the primary and the secondary surgeries was 65 months, with accumulated reoperation rates of 16.5%, 31.8%, and 57.2% after 5, 10, and 15 years, respectively. Obstruction was the most common indication for reoperation (37 patients, 25.0%). In a multivariable analysis, age <17 years at diagnosis (A1) (odds ratio [OR], 2.20; P = 0.023), penetrating behavior (B3) (OR, 4.39; P < 0.001), and no azathioprine use (OR, 2.87; P = 0.003) were associated with reoperation. Anti-TNF-alpha antibody use did not affect the reoperation rate (P = 0.767). CONCLUSION: We showed a high reoperation rate regardless of treatment with anti-TNF-alpha antibody, which indicates that recurrent surgery is still needed to cure patients with gastrointestinal Crohn diseases. Younger age at primary operation, penetrating behavior, and no azathioprine use were significant factors associated with reoperation for gastrointestinal Crohn disease. PMID- 26361618 TI - Colon Stricture After Ischemia Following a Robot-Assisted Ultra-Low Anterior Resection With Coloanal Anastomosis. AB - Four consecutive cases of a colonic stricture following a da Vinci robot-assisted ultra-low anterior resection (LAR) with coloanal anastomosis and diverting ileostomy for the treatment of rectal cancer are reported. The colonic strictures developed after early proximal colonic ischemia without anastomotic site leakage or disruption. All patients were treated with preoperative chemoradiation therapy. During the postoperative recovery period, patients developed colonic ischemia, presenting with a high, spiking fever, but without any symptoms of peritonitis. Patients were treated with conservative management (antibiotic therapy) and discharged after two weeks when in good condition. Several months after discharge, all four patients developed a long-segment colonic stricture from the anastomosis site to the distal colon. Management of the colon strictures, including the anastomotic site, involved colonic dilation with a Hegar dilator in an outpatient clinic for several months. The ileostomies in three patients could not be closed. PMID- 26361617 TI - Multiple Glomus Tumors of the Omentum. AB - A glomus tumor is a very rare neoplasm consisting of cells that resemble the modified smooth muscle cells of normal glomus bodies. Here, we report a case of a 39-year-old male with multiple omental glomus tumors. The patient underwent a complete resection of the glomus tumors. This is a rare case of omental glomus tumors, and to our knowledge, this patient is the first with multiple omental glomus tumors to be described. PMID- 26361619 TI - Commentary on "Insertion of Totally Implantable Central Venous Access Devices by Surgeons" - What Is the Role of Surgeons When Implanting a Totally Implantable Venous Access Device to Prevent Immediate Complications? PMID- 26361620 TI - Reply on "What Is the Role of Surgeons When Implanting a Totally Implantable Venous Access Device to Prevent Immediate Complications?". PMID- 26361621 TI - Erratum. AB - [This corrects the article on p. 23 in vol. 31, PMID: 25745623.]. PMID- 26361622 TI - Does preoperative heparin increase the postoperative bleeding risk in women undergoing prosthetic breast implant surgery? A review of the data from a single institution. AB - BACKGROUND: In 2008, the authors' institution adopted a policy requiring that all patients, regardless of preoperative risk, receive both sequential compression devices and a single preoperative subcutaneous 5000 unit injection of heparin. A previously published 12-year review at this same institution before this policy demonstrated a 1.5% 30-day postoperative incidence of hematoma in primary augmentation or delayed tissue expander based breast reconstructions. OBJECTIVE: To determine the incidence of postoperative bleeding complications associated with preoperative administration of 5000 units of subcutaneous heparin and compare that incidence with previously published data. METHODS: Patient data were collected prospectively and maintained in a secure database at a single institution with institutional review board approval. Current procedural terminology and International Classification of Diseases, Ninth Revision, coding was then used to identify all patients who received either primary breast augmentation or delayed tissue expander based breast reconstruction during a five year period. The primary outcome was the incidence of postoperative bleeding complication. A bleeding complication was defined as any hemorrhagic event that required a return to the operating room. RESULTS: The overall incidence of significant postoperative bleeding was 1.47% (five of 340 [1.16% augmentation, 2.50% expander]). Comparing the current results with the previously published data, demonstrated an OR of 0.98 (95% CI 0.38 to 2.55). CONCLUSION: In women undergoing primary breast augmentation or delayed tissue expander breast reconstruction, heparin prophylaxis did not increase the risk for significant postoperative bleeding compared with historical controls. PMID- 26361623 TI - Arteriovenous fistulas for microvascular head and neck reconstruction. AB - BACKGROUND: In head and neck cancer patients, multiple surgeries and radiation can leave the neck depleted of recipient vessels appropriate for microvascular reconstruction. The creation of temporary arteriovenous fistulas using venous interposition for subsequent microvascular reconstruction has rarely been reported in the head and neck. The authors report the largest series of temporary arteriovenous loops for head and neck reconstruction in vessel-depleted necks. METHODS: The authors performed a case series of major head and neck reconstructions using temporary arteriovenous fistulas with a saphenous vein graft. A subclavian surgical approach was used. All reconstructions were performed at least two weeks after the creation of the initial fistula. RESULTS: The authors have performed nine reconstructive cases for malignancy using five different free flaps. The subclavian and transerve cervical arteries were used, and the subclavian, internal jugular and cephalic veins were used for microanastomosis. Two cases of flap hematoma and one case of venous pedicle compression were recorded. No cases of flap failure were reported. CONCLUSIONS: Reconstruction using temporary arteriovenous fistulas is a reliable technique that can be used in the vessel-depleted neck, with excellent outcomes in experienced hands. PMID- 26361624 TI - Acute choke zone effects: Lessons from radioactive and fluorescent microspheres in a pig model muscle flap. AB - BACKGROUND: Choke vessels dilate and contract to regulate blood flow between adjacent arterial angiosomes. In skin flap surgery, when arterial inflow to an angiosome is ligated, choke vessels allow blood supply from an adjacent angiosome. In muscle flap surgery, the vascular anatomy is analogous to skin flaps; however, while it is established that the choke vessels will fully dilate irreversibly after two to three days, no study has yet analyzed the acute changes in each vascular region immediately following ligation of one pedicle. OBJECTIVE: To establish whether the choke vessels open or close immediately following ligation of a pedicle, and how this change affects blood flow in the adjacent proximal and distal vascular regions. METHODS: Radioactive and fluorescent microspheres in a pig model were used to study the regional intramuscular blood flow in each anatomical zone of a rectus abdominis flap. Blood flow measurements for each zone were calculated relative to the entire muscle at preligation, ligation and various times (15 min to 90 min) postligation. RESULTS: There was no statistically significant difference in blood flow across choke zones as a result of ligation. This signifies that the choke vessels do not significantly dilate to produce a statistically significant measureable change in blood flow. CONCLUSIONS: Given these results and previous literature findings, the anatomical presence of choke vessels in a muscle is the strongest determining factor for acute flap viability in surgery. PMID- 26361626 TI - Repositioned lateral crural flap technique for cephalic malposition in rhinoplasty. AB - BACKGROUND: Cephalic malposition of the lower lateral cartilage (CMLLC) is a relatively common anatomical variant, particularly in Middle Eastern patients. The characteristics of CMLLC include long alar creases, a boxy and ball-shaped nasal tip, parenthesis tip deformity and external valvular incompetence. The gold standard for correcting CMLLC is the lateral crural strut graft (Gunter graft), but many patients experience problems after this technique. OBJECTIVE: To evaluate the efficacy of the repositioned lateral crural flap (RLCF) technique in correcting CMLLC, and to discuss the cosmetic and functional results. METHODS: In the present study, 123 primary septorhinoplasty operations using the RLCF technique were performed between May 2012 and March 2013. The mean follow-up period was 11.4 months (range nine to 24 months). Four parameters were measured and compared pre- and postoperatively: the angle between the line connecting the maximum convexity of the lower lateral cartilage (LLC) to the tip-defining point and midline on each side (angle of rotation); the total distance between the maximum convexity of LLC right and left to midline (representing the size of the parenthesis deformity); satisfaction scale rating of the patients' nasal tip appearance; and the satisfaction scale rating of patients' breathing through their nostrils. RESULTS: The mean angle of the LLC to the midline significantly increased and the mean distance between the maximum convexities was significantly reduced, indicating correction of the malposition and reduction of the parenthesis deformity, respectively. The mean satisfactory scale ratings of nasal tip appearance and breathing quality were also significantly improved. CONCLUSION: CMLLC can be corrected using the RLCF technique, resulting in both aesthetic and functional improvements. PMID- 26361625 TI - Prevention of unfavourable effects of cigarette smoke on flap viability using botulinum toxin in random pattern flaps: An experimental study. AB - BACKGROUND: There are numerous clinical and experimental studies reporting unfavourable effects of cigarette smoke on skin flaps. OBJECTIVE: To investigate whether unfavourable effects of cigarette smoke on flap survival could be reduced by botulinum toxin type A. METHODS: Twenty-eight male Wistar albino rats (15 months of age, mean weight 210 g [range 180 g to 230 g]) were included. They were divided into four groups of seven animals each. The control group underwent the surgical procedure alone. Surgical procedure was performed after administration of botulinum toxin type A in the botulinum toxin (BTX) group, after exposure to cigarette smoke in the cigarette smoke (CS) group, and after BTX type A administration and exposure to CS in the CS+BTX (CS+BTX) group. Random pattern cutaneous flaps (3 cm * 9 cm) were elevated from the dorsum of all rats. Necrosis area was calculated in percentages (%) using Image J computer software. Tissue samples were examined histopathologically. RESULTS: The mean necrotic area in the control group (26%) and in the BTX group (21%) were similar (P=0.497), whereas administration of BTX type A significantly decreased flap necrosis area in the rats exposed to CS (the mean necrosis areas were 41.5% in the CS group, and 26% in the CS+BTX group; P<0.001). Histopathological examination findings corroborated the unfavourable effects of CS and preventive effects of BTX type A. CONCLUSION: Preoperative administration of BTX significantly enhanced flap viability in the rats exposed to CS. Further human studies are warranted to verify whether BTX type A could be used as an agent to reduce the risk of flap necrosis in patients who smoke. PMID- 26361627 TI - Minor surgery procedures: A retrospective review and prospective survey in a pediatric population. AB - OBJECTIVE: The present study evaluated minor surgery procedures undertaken by a single plastic surgeon at BC Children's Hospital (Vancouver, British Columbia) for patient and physician satisfaction, parent impressions, psychological concerns and complications. METHODS: Data were collected from a retrospective chart review and a prospective patient survey. Eligible subjects for the retrospective study included all pediatric patients undergoing minor surgery between May 2011 and April 2013. Parameters of interest included patient demographics, minor surgery specifics, complications and outcomes. Eligible subjects for the prospective patient survey included consecutive patients undergoing minor surgery between June 2013 and August 2013, as well as their parents. RESULTS: A total of 219 procedures were included in the retrospective review. The mean age of subjects was 13.1 years (range two weeks to 18 years). The median length of follow-up was 46 days (range four to 606 days). There were no major complications; however, 45 minor complications in 36 patients were found. Complications included crusting (4.6%), delayed wound healing (3.2%), hypersensitivity (2.3%), scar hypertrophy (1.8%), infection (0.9%) and other (7.8%). Outcomes were categorized as one of four outcomes: both satisfied (89.9%); patient satisfied but physician unsatisfied (0.8%); patient unsatisfied and physician satisfied (3.1%); and both unsatisfied (6.2%). In the prospective study, 32 subjects consented to participate in the survey. Of these subjects, 10 children and 12 parents responded to the questionnaires. Eighty-three percent of respondents indicated that their goals were accomplished by their procedure and that they would be willing to undergo minor surgery again. CONCLUSION: Minor surgery is possible and practical in pediatric plastic surgery clinics, with few complications and high patient and surgeon satisfaction. PMID- 26361628 TI - Development of an Acute Care Plastic Surgery Service in the Saskatoon Health Region: Effects on flexor tendon management. AB - BACKGROUND: The acute care surgery model has gained favour in general surgery, but has yet to be widely adopted in other specialties. An Acute Care Plastic Surgery (ACS) Service was recently implemented in the Saskatoon Health Region in an effort to improve trauma care. OBJECTIVE: To evaluate the impact of ACS on the management of flexor tendon lacerations. The authors hypothesize that ACS has resulted in more timely intervention, improved outcomes and decreased 'after hours' surgery. METHODS: A retrospective review of patients treated for flexor tendon lacerations from 2007 to 2013 was performed. Patients were stratified into two groups based on whether they received treatment before (group A) or after (group B) ACS implementation. Variables included dates and times of patient referral, consultation and tendon repair; postoperative complications; and admissions. A surgeon survey was administered on the perceived impact of ACS. RESULTS: Group A was more likely to have surgery performed after hours (P=0.0019) and be admitted to hospital (P=0.0211) compared with group B. Time from referral to consultation and injury-to-surgery interval were slightly increased post-ACS (Group B). Surgeons were highly satisfied with the new system, citing benefits to patients and surgeons. CONCLUSION: ACS was designed to improve trauma care, while favourably impacting surgeon workload. Surprisingly, the injury-to-surgery interval was slightly increased. However, this was not clinically significant and did not lead to increased postoperative complications. This finding was likely due to a favourable change in practice patterns observed after ACS implementation. ACS has resulted in fewer hospital admissions, decreased after hours surgeries and improved surgeon satisfaction. PMID- 26361629 TI - Cell-assisted lipotransfer in the clinical treatment of facial soft tissue deformity. AB - Cosmetic surgeons have experimented with a variety of substances to improve soft tissue deformities of the face. Autologous fat grafting provides significant advantages over other modalities because it leaves no scar, is easy to use and is well tolerated by most patients. Autologous fat grafting has become one of the most popular techniques in the field of facial plastic surgery. Unfortunately, there are still two major problems affecting survival rate and development: revascularization after transplantion; and cell reservation proliferation and survival. Since Zuk and Yosra developed a technology based on adipose-derived stem cells and cell-assisted lipotrophy, researchers have hoped that this technology would promote the survival and reduce the absorption of grafted fat cells. Autologous adipose-derived stem cells may have great potential in skin repair applications, aged skin rejuvenation and other aging-related skin lesion treatments. Recently, the study of adipose-derived stem cells has gained increased attention. More researchers have started to adopt this technology in the clinical treatment of facial soft tissue deformity. The present article reviews the history of facial soft tissue augmentation and the advent of adipose derived stem cells in the area of the clinical treatment of facial soft tissue deformity. PMID- 26361630 TI - Oral Exam. PMID- 26361631 TI - New capital acquisitions. PMID- 26361632 TI - Influenza Circulation in United States Army Training Camps Before and During the 1918 Influenza Pandemic: Clues to Early Detection of Pandemic Viral Emergence. AB - Background. Surveillance for respiratory diseases in domestic National Army and National Guard training camps began after the United States' entry into World War I, 17 months before the "Spanish influenza" pandemic appeared. Methods. Morbidity, mortality, and case-fatality data from 605 625 admissions and 18 258 deaths recorded for 7 diagnostic categories of respiratory diseases, including influenza and pneumonia, were examined over prepandemic and pandemic periods. Results. High pandemic influenza mortality was primarily due to increased incidence of, but not increased severity of, secondary bacterial pneumonias. Conclusions. Two prepandemic incidence peaks of probable influenza, in December 1917-January 1918 and in March-April 1918, differed markedly from the September October 1918 pandemic onset peak in their clinical-epidemiologic features, and they may have been caused by seasonal or endemic viruses. Nevertheless, rising proportions of very low incidence postinfluenza bronchopneumonia (diagnosed at the time as influenza and bronchopneumonia) in early 1918 could have reflected circulation of the pandemic virus 5 months before it emerged in pandemic form. In this study, we discuss the possibility of detecting pandemic viruses before they emerge, by surveillance of special populations. PMID- 26361634 TI - Effects of Exercise on Progranulin Levels and Gliosis in Progranulin-Insufficient Mice. AB - Loss-of-function mutations in progranulin (GRN) are one of the most common genetic causes of frontotemporal dementia (FTD), a progressive, fatal neurodegenerative disorder with no available disease-modifying treatments. Through haploinsufficiency, these mutations reduce levels of progranulin, a protein that has neurotrophic and anti-inflammatory effects. Increasing progranulin expression from the intact allele is therefore a potential approach for treating individuals with GRN mutations. Based on the well-known effects of physical exercise on other neurotrophic factors, we hypothesized that exercise might increase brain progranulin levels. We tested this hypothesis in progranulin heterozygous (Grn+/-) mice, which model progranulin haploinsufficiency. We housed wild-type and progranulin-insufficient mice in standard cages or cages with exercise wheels for 4 or 7.5 weeks, and then measured brain and plasma progranulin levels. Although exercise modestly increased progranulin in very young (2-month-old) wild-type mice, this effect was limited to the hippocampus. Exercise did not increase brain progranulin mRNA or protein in multiple regions, nor did it increase plasma progranulin, in 4- to 8-month-old wild-type or Grn+/- mice, across multiple experiments and under conditions that increased hippocampal BDNF and neurogenesis. Grn-/- mice were included in the study to test for progranulin-independent benefits of exercise on gliosis. Exercise attenuated cortical microgliosis in 8-month-old Grn-/- mice, consistent with a progranulin independent, anti-inflammatory effect of exercise. These results suggest that exercise may have some modest, nonspecific benefits for FTD patients with progranulin mutations, but do not support exercise as a strategy to raise progranulin levels. PMID- 26361633 TI - Genetic Resistance to Malaria Is Associated With Greater Enhancement of Immunoglobulin (Ig)M Than IgG Responses to a Broad Array of Plasmodium falciparum Antigens. AB - Background. People of the Fulani ethnic group are more resistant to malaria compared with genetically distinct ethnic groups, such as the Dogon people, in West Africa, and studies suggest that this resistance is mediated by enhanced antibody responses to Plasmodium falciparum antigens. However, prior studies measured antibody responses to <0.1% of P falciparum proteins, so whether the Fulani mount an enhanced and broadly reactive immunoglobulin (Ig)M and IgG response to P falciparum remains unknown. In general, little is known about the extent to which host genetics influence the overall antigen specificity of IgM and IgG responses to natural infections. Methods. In a cross-sectional study in Mali, we collected plasma from asymptomatic, age-matched Fulani (n = 24) and Dogon (n = 22) adults with or without concurrent P falciparum infection. We probed plasma against a protein microarray containing 1087 P falciparum antigens and compared IgM and IgG profiles by ethnicity. Results. We found that the breadth and magnitude of P falciparum-specific IgM and IgG responses were significantly higher in the malaria-resistant Fulani versus the malaria susceptible Dogon, and, unexpectedly, P falciparum-specific IgM responses more strongly distinguished the 2 ethnic groups. Conclusions. These findings point to an underappreciated role for IgM in protection from malaria, and they suggest that host genetics may influence the antigen specificity of IgM and IgG responses to infection. PMID- 26361635 TI - Nanorobotic Applications in Medicine: Current Proposals and Designs. AB - Advances in technology have increased our ability to manipulate the world around us on an ever-decreasing scale. Nanotechnologies are rapidly emerging within the realm of medicine, and this subfield has been termed nanomedicine. Use of nanoparticle technology has become familiar and increasingly commonplace, especially with pharmaceutical technology. An exciting and promising area of nanotechnological development is the building of nanorobots, which are devices with components manufactured on the nanoscale. This area of study is replete with potential applications, many of which are currently being researched and developed. The goal of this paper is to give an introduction to the emerging field of nanorobotics within medicine, and provide a review of the emerging applications of nanorobotics to fields ranging from neurosurgery to dentistry. PMID- 26361637 TI - Delays in Patient Waiting Times at U.S. Department of Veterans Affairs Hospitals in Cities with Sizeable Hispanic Populations. PMID- 26361639 TI - Patients and practice guidelines: Keeping eyes on the horizon. PMID- 26361640 TI - A treatable mimicker of cholangiocarcinoma. PMID- 26361636 TI - Protein-Inhibitor Interaction Studies Using NMR. AB - Solution-state NMR has been widely applied to determine the three-dimensional structure, dynamics, and molecular interactions of proteins. The designs of experiments used in protein NMR differ from those used for small-molecule NMR, primarily because the information available prior to an experiment, such as molecular mass and knowledge of the primary structure, is unique for proteins compared to small molecules. In this review article, protein NMR for structural biology is introduced with comparisons to small-molecule NMR, such as descriptions of labeling strategies and the effects of molecular dynamics on relaxation. Next, applications for protein NMR are reviewed, especially practical aspects for protein-observed ligand-protein interaction studies. Overall, the following topics are described: (1) characteristics of protein NMR, (2) methods to detect protein-ligand interactions by NMR, and (3) practical aspects of carrying out protein-observed inhibitor-protein interaction studies. PMID- 26361642 TI - Effects of music listening on stress, anxiety, and sleep quality for sleep disturbed pregnant women. AB - Prenatal sleep disturbance has been associated with undesirable birthing outcomes. To determine the effectiveness of listening to music at home in improving sleep quality, 121 Taiwanese pregnant women with poor sleep quality (Pittsburgh Sleep Quality Index [PSQI] score > 5) were systematically assigned, with a random start to music listening (n = 61) or control (n = 60) group. Participants in the music listening group self-regulated listening to music in addition to receiving general prenatal care similar to that in the control group for 2 weeks. The PSQI and State-Anxiety Inventory were used to assess outcomes. ANCOVA analyses were used with the pretest scores as covariates and showed significant improvement in sleep quality, stress, and anxiety in the music listening group compared with the control group. The most frequently used music genre by participants in the experimental group was lullabies, followed by classical music and crystal baby music. This study supported the theory that 2 week music listening interventions may reduce stress, anxiety, and yield better sleep quality for sleep-disturbed pregnant women. The analysis of participants' journals also implied that the expectant mothers' choices of musical genres may correlate more with perceived prenatal benefits or the desire to interact with their unborn child. PMID- 26361643 TI - Life promises and 'failed' family ties: expectations and disappointment within a clinical trial (Ivory Coast). AB - Building on fieldwork carried out in a clinical trial looking at early antiretroviral treatment for HIV in Abidjan, this paper aims to analyse the way relations emerge during trials and the consequences of the end of participation. Instead of discussing it using the register of ethics, understood as a universal set of principles, the trial is analysed for what it means locally for its actors, mainly patients. From this standpoint, the trial can be defined as both a promise of life and of new possibilities embodied in what is often described as new family ties. How are such ties formed and what does it mean when these ties are broken at the end of patient participation? Discussing the failure of family ties commented upon by patients and dealt by physician researcher is a way to look at ethics from below. PMID- 26361644 TI - Prediction of Cyclic Fatigue Life of Nickel-Titanium Rotary Files by Virtual Modeling and Finite Elements Analysis. AB - INTRODUCTION: The finite element method (FEM) has been proposed as a method to analyze stress distribution in nickel-titanium (NiTi) rotary instruments but has not been assessed as a method of predicting the number of cycles to failure (NCF). The objective of this study was to predict NCF and failure location of NiTi rotary instruments by FEM virtual simulation of an experimental nonstatic fatigue test. METHODS: ProTaper Next (PTN) X1, X2, and X3 files (Dentsply Maillefer, Baillagues, Switzerland) (n = 20 each) were tested to failure using a customized fatigue testing device. The device and file geometries were replicated with computer-aided design software. Computer-aided design geometries (geometric model) were imported and discretized (numeric model). The typical material model of an M-Wire alloy was applied. The numeric model of the device and file geometries were exported for finite element analysis (FEA). Multiaxial random fatigue methodology was used to analyze stress history and predict instrument life. Experimental data from PTN X2 and X3 were used for virtual model tuning through a reverse engineering approach to optimize material mechanical properties. Tuned material parameters were used to predict the average NCF and failure locations of PTN X1 by FEA; t tests were used to compare FEA and experimental findings (P < .05). RESULTS: Experimental NCF and failure locations did not differ from those predicted with FEA (P = .098). CONCLUSIONS: File NCF and failure location may be predicted by FEA. Virtual design, testing, and analysis of file geometries could save considerable time and resources during instrument development. PMID- 26361646 TI - Prognostic Value of Anemia and C-Reactive Protein Levels in Diffuse Large B-Cell Lymphoma. AB - PURPOSE: To determine the prognostic value of pretreatment anemia, pretreatment elevated C-reactive protein (CRP) levels, and 6-month posttreatment anemia in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) treated with rituximab, cyclophosphamide, hydroxydaunorubicin, Oncovin, and prednisolone (R CHOP). PATIENTS AND METHODS: A total of 104 patients with newly diagnosed DLBCL were retrospectively included. Pretreatment hemoglobin and CRP levels and 6-month posttreatment hemoglobin levels were measured. Cox regression analyses were used to determine the associations of laboratory assessments and National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) risk groups with progression-free survival (PFS) and overall survival (OS). RESULTS: Pretreatment anemia, elevated pretreatment CRP levels, and higher risk NCCN-IPI groups were significantly associated with reduced PFS and OS (P = .001 and P = .003 for pretreatment anemia, P = .035 and P = .029 for elevated CRP, and P < .001 and P < .001 for higher risk NCCN-IPI groups). On multivariate Cox regression analysis, only the NCCN-IPI risk group remained as an independent significant predictor for PFS (P < .001) and OS (P < .001). In the subgroup of patients in complete remission 6 months after chemotherapy (n = 80), 6-month posttreatment anemia was significantly associated with reduced PFS (P = .046) but not OS (P = .062), and higher risk NCCN-IPI groups were significantly associated with both reduced PFS (P = .008) and OS (P = .017). On multivariate Cox regression analysis, only the NCCN-IPI group remained an independent significant predictor for PFS (P = .008) and OS (P = .017). CONCLUSION: Pretreatment anemia, pretreatment CRP levels, and 6-month posttreatment anemia are significantly associated with poor outcome, but were not proven to be of additional prognostic value to the current risk stratification index for DLBCL. PMID- 26361645 TI - Cost-Effectiveness Analysis of Treating Acute Promyelocytic Leukemia Patients With Arsenic Trioxide and Retinoic Acid in the United States. AB - INTRODUCTION: This study estimated the cost-effectiveness of arsenic trioxide (ATO) added to all-trans retinoic acid (ATRA) when used in first-line acute promyelocytic leukemia (APL) treatment. MATERIALS AND METHODS: A Markov cohort model was developed with 3 states: stable disease (during first- or second-line treatment), disease event, and death. Newly diagnosed patients with low- to intermediate-risk APL were included and each month could remain in their current health state or move to another. Treatment consisted of ATO + ATRA, ATRA + idarubicin (IDA), or ATRA + cytarabine (AraC) + additional chemotherapy. After an initial disease event, patients discontinued first-line therapy and switched to a second-line ATO regimen. Efficacy and safety data were obtained from published trials; quality of life/utility estimates were obtained from the literature; costs were obtained from US data sources. Costs and outcomes over time were used to calculate incremental cost-effectiveness ratios (ICERs). Deterministic and probabilistic sensitivity analyses were conducted. RESULTS: Compared to ATRA + AraC + additional chemotherapy, ATRA + IDA treatment had ICERs of $2933 per life year (LY) saved and $3122 per quality-adjusted life-year (QALY) gained. Compared to the ATRA + IDA regimen, first-line ATO + ATRA treatment had ICERs of $4512 per LY saved and $5614 per QALY gained. Results were sensitive to changes in pharmacy costs of the ATO + ATRA regimen during consolidation. CONCLUSION: The ATO + ATRA regimen is highly cost-effective compared to ATRA + AraC + additional chemotherapy or ATRA + IDA in the treatment of newly diagnosed low- to intermediate-risk APL patients. PMID- 26361647 TI - Outcomes Among High-Risk and Standard-Risk Multiple Myeloma Patients Treated With High-Dose Chemotherapy and Autologous Hematopoietic Stem-Cell Transplantation. AB - BACKGROUND: Conventional cytogenetics and interphase fluorescence in-situ hybridization (FISH) identify a high-risk multiple myeloma population characterized by poor response and short survival. PATIENTS AND METHODS: We compared outcomes between high-risk and standard-risk myeloma patients who underwent autologous hematopoietic stem-cell transplantation (auto-HCT) at our institution between January 2005 and December 2009. High-risk myeloma was defined as -13/del(13q) or hypodiploidy in at least 2 metaphases of conventional cytogenetics, or -17/del(17p), t(4;14), t(14;16), t(14;20), hypodiploidy (< 45 chromosomes excluding -Y), or chromosome 1 abnormalities (+1q, -1p, t(1;x)) on FISH or conventional cytogenetics. RESULTS: Of 670 myeloma patients, 74 (11%) had high-risk myeloma. These high-risk patients had significantly lower overall response rates (74% vs. 85%; P < .01), shorter median progression-free survival (10.3 vs. 32.4 months; P < .001), and shorter overall survival (28 months vs. not reached; P < .001) than the standard-risk patients. Having only 1 high-risk cytogenetic abnormality or experiencing at least very good partial remission after auto-HCT independently predicted improved progression-free survival and overall survival (P < .05) in high-risk patients. CONCLUSION: Even in an era of novel therapies, cytogenetically identified high-risk myeloma patients have worse prognoses than standard-risk myeloma patients after auto-HCT, and having more than 1 high-risk cytogenetic abnormality further reduces survival. PMID- 26361648 TI - "The women, they maltreat them... therefore, we cannot assure that the future society will be good": Male perspectives on gender-based violence: A focus group study with young men in Haiti. AB - The purpose of this study was to explore the perceptions of violence against women (VAW) held by Haitian men to gain a better understanding of why VAW occurs. Women in Haiti have experienced significant violence, both before and following the 2010 earthquake. Fifteen men aged 26 to 47 participated in a focus group. The data revealed three themes: men's beliefs about VAW and its context, factors influencing VAW, and recommended interventions. When approaching VAW, men must be part of the collective effort. Their insights are valuable when planning and implementing interventions to decrease VAW in Haiti and worldwide. PMID- 26361651 TI - Beyond the Officially Sacred, Donor and Believer: Religion and Organ Transplantation. AB - Religious concerns might represent an important issue when donation for transplantation is discussed. Even if no religious tradition formally forbids organ donation and transplantation, members of the same religious group may have differing and often conflicting opinions in their own interpretation of how their religion encourages and/or supports organ donation and transplantation, as discussed in this article. It also should be considered that even if a religion refuses to define concrete rules about organ donation and transplantation, there are a great number of factors that may influence the decision-making process. Examples may include negative perceptions of the cutting and removal of organs or ignorance about the transplantation system, both of which would influence the decision-making process concerning transplantation. Knowledge of these facts may provide useful information, perhaps increasing transplant numbers. PMID- 26361649 TI - Inducible NO synthase is constitutively expressed in porcine myocardium and its level decreases along with tachycardia-induced heart failure. AB - BACKGROUND: The adverse effects of oxidative stress and the presence of proinflammatory factors in the heart have been widely demonstrated mainly on rodent models. However, larger clinical trials focusing on inflammation or oxidative stress in heart failure (HF) have not been carried out. This may be due to differences in the anatomy and physiology of the cardiovascular system between small rodents and large mammals. Thus, we investigated myocardial inflammatory factors, such as inducible NO synthase (iNOS) and oxidative stress indices in female pigs with chronic tachycardia-induced cardiomyopathy. METHODS: Homogenous female siblings of Large White breed swine (n=15) underwent continuous right ventricular (RV) pacing at 170bpm, whereas five sham-operated subjects served as controls. In the course of RV pacing, animals developed a clinical picture of HF and were euthanized at subsequent stages of the disease: mild, moderate and severe HF. Left ventricle (LV) sections were examined with electron microscopy. The relative expression of iNOS in LV was determined by quantitative PCR. The protein level of iNOS was determined by Western blotting and immunohistochemistry. The level of the S-nitrosylated (S-NO) protein in LV was determined after S-NO moieties were substituted by biotin, followed by a colorimetrical detection with streptavidin. Malondialdehyde (MDA), a marker of lipid peroxidation, was evaluated in the LV and serum using thiobarbituric acid. The aconitase activity (based on measurement of the concomitant formation of NADPH from NADP(+)), a marker of oxidative stress, was analyzed in mitochondrial and cytosolic LV fractions. The concentration of interleukin-1beta (IL-1beta) was measured in LV homogenates using enzyme-linked immunosorbent assay. RESULTS: RV pacing resulted in an impairment of LV systolic function, LV dilatation and neurohormonal activation. The electron microscopy revealed abnormalities within the cardiomyocytes of failing hearts, i.e. swollen mitochondria and myofibril derangement. iNOS was expressed in the control LV myocardium. The development of HF was accompanied by a decrease in iNOS mRNA (P<.05), which was also reflected at a protein level, and a decrease in the protein S-nitrosylation (P<.05). Both iNOS mRNA and S-NO relative moiety levels were inversely related to the dilatation of the LV (P<.05). There was no difference in the concentration of MDA in the LV and serum. Similarly, no differences in the concentration of IL-1beta LV were found between diseased and healthy animals. Aconitase activity was decreased only in the LV mitochondrial fraction of pigs with severe HF. CONCLUSIONS: iNOS was shown to be constitutively expressed within porcine LV. Its level decreases during the progression of systolic nonischemic HF in the pig model. Thus, it can be assumed that an up-regulation of proinflammatory factors is not involved in porcine tachycardia-induced cardiomyopathy and that the impact of oxidative stress may be restricted to the mitochondria in this HF model. PMID- 26361652 TI - Effectiveness of an Education Program on Donation and Transplant Aimed at Students of the Nursing Degree Course. AB - BACKGROUND: Health workers' awareness and knowledge of transplant medicine can improve people's sensitivity and reduce their degree of opposition to donations. The medical literature contains numerous examples of education programs aimed at university students. This work describes the experience of an education program for students of the second and third year of a nursing degree course. METHODS: From April to September 2013, an education program was set up for 80 university students. It was divided into 3 stages: group self-learning based on prearranged topics, sharing of the results, and participation in the final seminar. The effectiveness was assessed according to a pretest/posttest design. RESULTS: The first questionnaire contained 19 questions, and the second contained 27. The questions were subdivided into specific areas: subjective knowledge, objective knowledge, attitude, awareness, participation in the event, evaluation of the information material handed out, and appreciation of the tools used. There was a significant increase for items relating to knowledge, whereas awareness and attitude (already high at the start of the program) showed no changes. After the program, many students discussed the question of donation with their relatives and friends, and about 70% filled in a donor card. The students expressed a highly positive opinion of the initiative and the tools used. CONCLUSIONS: The initiative proved its validity, improving subjective and objective knowledge to a statistically significant extent and also increasing awareness and attitude. The students' evaluation was extremely positive. PMID- 26361654 TI - Organ Allocation Policies According to EU National Bioethics Committees: A Comparison. AB - The opinions expressed by European National Bioethics Committees (NBCs) on organ transplants were examined. Very few opinions specifically addressed the issue of allocation, and those that did revealed not only conflicts between clinical criteria and ethical principles but also potential competition between ethical principles that are equally important and deserving of respect. An examination of the various opinions showed agreement on the need to balance conflicting criteria and principles, as well as the diversity of the available practical options. Although NBCs agree that the choice of allocation policies should focus on therapeutic criteria while also considering other parameters, such as justice, clinical usefulness, and waiting period, the relative weights to be attributed to each vary among committees. PMID- 26361653 TI - Overextended Criteria Donors: Experience of an Italian Transplantation Center. AB - The increasing gap between the number of patients who could benefit from liver transplantation and the number of available donors has fueled efforts to maximize the donor pool using marginal grafts that usually were discarded for transplantation. This study included data of all patients who received decreased donor liver grafts between January 2004 and January 2013 (n = 218) with the use of a prospectively collected database. Patients with acute liver failure, retransplantation, pediatric transplantation, and split liver transplantation were excluded. Donors were classified as standard donor (SD), extended criteria donor (ECD), and overextended criteria donor (OECD). The primary endpoints of the study were early allograft primary dysfunction (PDF), primary nonfunction (PNF), and patient survival (PS), whereas incidence of major postoperative complications was the secondary endpoint. In our series we demonstrated that OECD have similar outcome in terms of survival and incidence of complication after liver transplantation as ideal grafts. PMID- 26361655 TI - Paid Organ Donation: An Italian Perspective. AB - The only countries that have allowed financial incentives for organ donation are Iran since 1988, and later on, Singapore and Saudi Arabia. In Europe, and of course in Italy, financial incentives for donors are prohibited. The author has completed extensive research via the Internet (PubMed) of worldwide scientific literature on paid organ donation, also researching studies concerning public opinion on organ commercialism and "regulated markets". Italian transplant laws also have been reported and analyzed. PMID- 26361656 TI - Liver Graft Allocation by Means of a New, Regionally Shared "Mixed" Model: The Experience in Lazio. AB - INTRODUCTION: Since 2013, the regional network of transplantation centers "LAZIO TRANSPLANT" have adopted a new, mixed system for the allocation of liver grafts. METHODS: The organs from donors aged <65 are assigned to patients with higher Model for End-stage Liver Disease (MELD) scores on a common regional waiting list, whereas those from donors aged >65 are allocated to patients with higher MELD scores on a specific local waiting list (LWL) at each center, on a rotational basis. RESULTS: The new mixed allocation model grants a more rational allocation of the "standard" organs to the patients with the actual worst MELD score in the entire region, avoiding the possibility that a patient in relatively better clinical condition might be transplanted before a more severely ill patient on another center's waiting list. Nonstandard organs, presenting slightly increased transplant risks, are still allocated on a rotational basis among the different transplant centers, ensuring them the possibility to select, on the basis of a global clinical risk evaluation, those patients in their LWL whose MELD score would not grant any possibility to compete for the "standard" organ allocation. CONCLUSIONS: The application of the new model had no negative impact on the overall number of transplants performed or on the global list-satisfaction percentages, but has slightly improved the cumulative mortality of the patients in the waiting list, granting to the clinically worst patients a prompt graft allocation, independent of the local center belonging. PMID- 26361657 TI - De Novo Solid Tumors After Kidney Transplantation: Is It Time for a Patient Tailored Risk Assessment? Experience From a Single Center. AB - BACKGROUND: Progress in immunosuppressive therapy and perioperative techniques has improved the survivals of both grafts and patients. The patient, however, is exposed to the risks of aging and side effects of immunosuppression. De novo tumors are the 2nd cause of death in the organ transplant population. The aim of this study was to evaluate whether the current accepted guidelines for the pre transplantation study and the post-transplantation follow-up have been effective, in our kidney transplant population, regarding early detection and treatment, improving prognosis, and reducing mortality of some curable neoplastic diseases. METHODS: We considered de novo tumors in kidney transplant patients from 1995 to 2010 (n = 636) excluding hematologic and nonmelanoma skin tumors from our study. RESULTS: There were 64 de novo tumors in 59 patients out of 636 kidney transplant patients; 29.68% were urogenital cancer, 26.56% gastrointestinal cancer, 12.5% melanoma, 6.25% lung cancer, 6.25% biliopancreatic cancer, 4.68% visceral Kaposi sarcoma, 4.68% breast cancer, 4.68% thyroid cancer, 1 pleural mesothelioma, 1 meningioma, 1 merkeloma. Twenty patients died because of cancer. Ten patients had a late de novo tumor diagnosis, when the stage of tumor was advanced and not suitable for curative treatment. CONCLUSIONS: Because of the increased neoplastic risk, we consider it mandatory to carry out a meticulous screening and to implement pre-transplantation study concerning this increased neoplastic risk population to detect a subgroup of patients presenting the highest risk to improve their outcome. PMID- 26361658 TI - p-Cresol and Cardiovascular Risk in Kidney Transplant Recipients. AB - p-Cresol Sulphate (pCS) is a uremic toxin that originates exclusively from dietary sources and has a high plasma level related to chronic kidney disease (CKD) and cardiovascular disease (CVD). The aim of our study was to evaluate the plasma levels of pCS in kidney transplant recipients (KTRs) related to estimated glomerular filtration rate (eGFR), traditional risk factors, cardiovascular clinical events and endothelial progenitor cells (EPCs), bone marrow-derived cells for the vascular repair system. We considered 51 KTRs and 25 healthy blood donors (HBDs). pCs levels were analyzed using high-performance liquid chromatography (HPLC) coupled with mass spectrometry with an electrospray ionization (ESI) (LC/ESI-MS/MS) on a triple-quadrupole; EPCs were analyzed using flow cytometric analysis. eGFR was 52.61 +/- 19.9 mL/min/1.73 m(2) in KTRs versus 94 +/- 21 mL/min/1.73 m(2) in HBDs. We did not find differences in pCS levels between KTRs and HBDs. Levels of pCS were inversely related with eGFR in KTRs and pCS levels were significantly lower in KTRs with eGFR <30 mL/min/1.73 m(2) versus eGFR >30 mL/min/1.73 m(2). Furthermore, there was a difference in pCS levels between eGFR <30 mL/min/1.73 m(2) of KTRs compared with HBDs. Levels of pCS were almost significantly influenced by the presence of a previous vascular event and were inversely related with mature EPCs. These findings suggest that KTRs should not have higher CVD risk than HBDs and their physiological vascular repair system appears to be intact. In KTRs the reduction of eGFR also increased pCS levels and reduced EPCs numbers and angiogenesis capacity. In summary, pCS acts as an emerging marker of a uremic state, helping assess the global vascular competence in KTRs. PMID- 26361659 TI - Expanding the Living Donor Pool "Second Act": Laparoscopic Donor Nephrectomy and ABO-Incompatible Kidney Transplantation Improve Donor Recruitment. AB - BACKGROUND: To safely expand our living donor pool, we recently decided to work on 3 areas: analysis of causes of exclusion of potential donors, the results of which we recently published, introduction of laparoscopic donor nephrectomy (LDN), and ABO-incompatible (ABOi) transplantation. We sought to determine the impact of the new strategy on living donor recruitment and transplantation during over a 10-year period at a single institution. METHODS: From January 2005 to September 2014, we evaluated 131 living donors. Of these, 80 (61%) were genetically related, 51 (39%) unrelated, 119 (91%) ABO compatible (ABOc), 12 ABOi (9%). The analysis was divided into 2 eras: era 1, 2005-2010 (n = 53) included the use of open lumbotomy and acceptance of ABOc only; and era 2, 2011-2014 (n = 78), which saw the introduction of LDN and ABOi transplantation. RESULTS: Forty five (34%) potential candidates successfully donated, 67 (51%) were excluded, and 19 (15%) were actively undergoing evaluation. Overall, 53 potential donors were evaluated in era 1 (8.8 donors/year), 78 in era 2 (19.5 donors/year). There were fewer excluded donors in era 2 vs era 1 (62% era 1 vs 44% era 2), and living donor kidney transplantation (LDKT) significantly increased in era 2 vs era 1 (3.3/year era 1 vs 7.1/year era 2). The establishment of an ABOi LDKT program led to a 15% increase of evaluations in era 2 (12/78 donors). CONCLUSIONS: LDN along with ABOi LDKT allowed for an improvement in recruitment of living donors and corresponding LDKT. PMID- 26361660 TI - Effect of Donor- and Recipient-Related Factors on Arterial Resistance Index After Kidney Transplant. AB - BACKGROUND: The assessment of color Doppler resistance index (RI) of the intra renal arteries has been shown to be a good predictor of short-term and long-term graft survival after kidney transplant. In this study, we investigated the influence of donor- and recipient-related factors on RI evaluated early after kidney transplant. METHODS: We prospectively analyzed 90 kidney transplant patients who underwent RI assessment within the first month after the transplant, subdivided into 2 groups according their RI values lower (group A) or higher (group B) than 0.646 (median value). RESULTS: Patients in group A had a lower human leukocyte antigen (HLA) mismatch number (3.3 +/- 1 versus 3.9 +/- 0.9, P = .007) and were significantly younger (42.8 +/- 11 years versus 47.8 +/- 11 years, P = .03) than patients in group B. All the others variables examined were not significantly different between the 2 groups. Multivariate logistic regression analysis confirmed that HLA mismatch number (P = .03) and recipient age (P = .03) are independent predictors of RI. CONCLUSIONS: Our data suggest that HLA mismatches and donor age can influence recipient kidney vascular resistance in the early period after transplantation. PMID- 26361661 TI - A Study on Emotional-Affective Aspects and the Perception of General Health in Kidney Transplant Subjects. AB - BACKGROUND: Transplantation has profound psychological implications. Psychodiagnostic assessments with structured instruments (scales, questionnaires) may be insufficient for bringing out the deeper aspects of the personality. PATIENTS AND METHODS: Thirty kidney transplant recipients underwent the Thematic Apperception Test to detect significant variables hypothetically related to characteristics of the study sample and the SF-36 to assess quality of life. RESULTS: The variable of Thematic Apperception Test (TAT) "communication difficulties" was significantly correlated with the dimensions of the SF-36 "emotional role functioning," "social activities," and "mental health." The dimension of SF-36 "general health" did not interfere with the variable of TAT "constricted effect." CONCLUSIONS: This study is considered to be particularly useful in detecting the emergence of "removed difficulties" that transplanted subjects are not inclined to recognize. The analysis of these aspects is necessary to plan individualized psychotherapy pathways. PMID- 26361662 TI - Long-Term Prognostic Impact of Contrast-Enhanced Ultrasound and Power Doppler in Renal Transplantation. AB - BACKGROUND: Contrast-enhanced ultrasound (CEUS) and power Doppler ultrasound (US) are established tools in the study of acute renal allograft (RA) dysfunction. The aim of this study was to investigate their long-term prognostic impact. MATERIALS AND METHODS: A total of 39 kidney recipients underwent CEUS and US at 5 and 15 days and at 1, 3, 6, and 12 months after grafting, with yearly clinical, laboratory, and US follow-up for a total of 4 years. CEUS analysis according to the gamma variate model was performed on cortical and medullary regions. Patients were divided into 2 subsets: death or graft failure vs patients with functioning grafts; higher vs lower than 50% glomerular filtration rate (GFR) reduction from the first month to the fourth year after grafting. Receiver-operator characteristic (ROC) analysis for death/graft failure and 50% GFR reduction events was performed for variables with significant differences between groups (t test) or with significant correlation to GFR (Pearson correlation). RESULTS: ROC analysis confirms the reliability of clinical and radiologic variables for the evaluation of long-term graft survival or of GFR reduction, with high sensitivity (for resistive index) or specificity (for GFR, medullary peak, and regional blood flow). CONCLUSIONS: Combining CEUS and US allows the evaluation of long-term RA function in terms of GFR reduction and graft survival. Resisitive-indexes show a good sensitivity, relating to kidney disfunction, while CEUS parameters show a good specificity, identifiying well-perfused grafts. PMID- 26361663 TI - Plasmapheresis, Photopheresis, and Endovenous Immunoglobulin in Acute Antibody mediated Rejection in Kidney Transplantation. AB - INTRODUCTION: Acute antibody-mediated rejection (AAMR) is the subject of much research. It is diagnosed by C4d staining at biopsy and circulating donor specific antibodies (DSA). The combination of intensive plasmapheresis and intravenous immunoglobulin (IVIG) has been recognized as an effective treatment for AAMR. We report our single-center experience on AAMR treatment. MATERIALS AND METHODS: We treated 23 transplanted patients (group A) with protein-A immunoadsorption (IA) and 7 patients (group B) with double-filtration plasmapheresis. All patients were treated with IVIG (400 mg/kg/d). Basic immunosuppression included cyclosporine, steroids, azathioprine, and antilymphocyte globulin or monoclonal antibodies (OKT3). A subgroup of 3 patients (3/7; group B1) was treated with photopheresis. RESULTS: In both groups, the mean number of extracorporeal procedures was 7.3 +/- 4.5 and 5.5, respectively; the mean duration of treatment was 12.3 +/- 10.2 and 14.5 days, respectively. In group A, we observed negative cross-matching in 96% after mean of 18 days; 1 patient died from sepsis, and 6 lost their grafts. In group B, negative circulating DSA were observed in all patients after a mean of 25 days, and 1 patient lost their allograft. CONCLUSIONS: In our observation, the 2 extracorporeal procedures had similar effects in terms of graft survival, DSA removal, and cross-match negativity (group A 74% vs 86%; 95.6% vs 100%). IA was faster for DSA removal. In our opinion, the higher costs of IA suggests its use just in high-risk cases, such as in hyperimmune or sensitized patients. Further studies are necessary to improve our knowledge. PMID- 26361664 TI - Negative Pressure Wound Treatment of Infections Caused By Extensively Drug Resistant Gram-Negative Bacteria After Liver Transplantation: Two Case Reports. AB - Although survival after liver transplantation (LT) has progressively improved over the last years, an increased prevalence of clinically relevant infections in LT patients is well documented. In particular, the spread of infections sustained by extensively drug-resistant bacteria (XDR) produced an increase in the incidence of wound infections. Implementation of treatments for these life threatening events is mandatory. This study describes 2 LT patients in whom XDR wound infection was effectively treated using negative pressure wound treatment (NPWT) combined with targeted local and systemic antibiotic therapy. Over the last 3 years, 2 of 8 patients with XDR infection admitted to our unit developed wound infection caused by XDR Klebsiella pneumoniae (KP-XDR). Positive results of the abdominal fluid culture and of the wound swab for KP-XDR were followed by sepsis. In both cases wound debridement was required and deep fascial layer dehiscence was detected. Combination antibiotic therapy was administered for sepsis treatment and, after failure of conventional NPWT, a NPWT with local instillation (NPWTi; V.A.C.-Ulta/VeraFlo-Instillation Therapy-KCI USA, Inc., San Antonio, TX, USA) of colistin-rifampicin was applied. After NPWTi application a reduction in bacterial load and exudate was observed with reduction in inflammatory markers. A complete healing of wound was achieved and both patients are currently alive. Instillation and NPWT are widely discussed in the literature. Results of the present study indicate beneficial effects of NPWT combined with targeted local and systemic antibiotic therapy; in both cases a life-threatening complication was cured. We consider local instillation of selected antibiotics applied to NPWTi a valuable tool for deep wound infection sustained by XDR bacteria. PMID- 26361665 TI - Diagnosis and Management of Hepatic Artery Complications After Liver Transplantation. AB - BACKGROUND: We assessed the usefulness of color Doppler imaging in diagnosis and monitoring hepatic artery complications after liver transplantation. METHODS: Subjects were 421 liver transplant recipients who underwent serial ultrasound (US) color Doppler evaluations of the hepatic arteries after surgery. RESULTS: We saw 4 hepatic arterial complications after liver transplantation (13 thrombosis, 29 stenosis, 2 kinking, 2 pseudo-aneurysm, and 2 pseudo-aneurysm rupture). All subjects underwent US color Doppler examination periodically after surgery. In 6 cases of early thrombosis, hepatic arterial obstruction was diagnosed with absence of Doppler signals; in the other 7 cases (late hepatic artery thrombosis), thrombosis was suspected for the presence of intra-parenchymal "tardus-parvus" waveforms. In all of the cases, computed tomography angiography showed obstruction of the main arterial trunk and the development of compensatory collateral circles (late hepatic artery thrombosis). In 10 of the 29 cases of stenosis, Doppler ultrasonography examination revealed stenotic tract and intra hepatic tardus-parvus waveforms; in 17 stenosis cases, the site of stenosis could not be identified, but intra-parenchymal tardus-parvus waveforms were recorded. In 2 patients, hepatic artery stenosis occurred with ischemic complications. CONCLUSIONS: The use of US color Doppler examination allows the early diagnosis of hepatic arterial complications after liver transplantation. Tardus-parvus waveforms indicated severe impairment of hepatic arterial perfusion from either thrombosis or severe stenosis. The presence of these indirect signs enhanced the accuracy of color Doppler diagnosis, and detection should prompt therapy. PMID- 26361666 TI - Simultaneous Liver-Kidney Transplantation in Adults: A Single-center Experience Comparing Results With Isolated Liver Transplantation. AB - BACKGROUND: After introduction of the Model for End-Stage Liver Disease (MELD) score in 2002, a worldwide increasing number of simultaneous liver-kidney transplantations (SLKTx) has been observed. However, organ shortage puts into question the allocation of 2 grafts to 1 recipient. This retrospective, single center study compared SLKTx results with isolated liver transplantation (LTx). METHODS: Between 1995 and 2013, 37 SLKTx were performed in adult recipients. Every SLKTx was matched by donor age (+/-5 years) and transplantation date with 2 LTx (n = 74). Pretransplant, intraoperative, and post-transplant variables were collected; liver graft and patient survivals were calculated. RESULTS: As expected, donor age was similar in the 2 groups (median, 39.7 years), whereas serum creatinine level, glomerular filtration rate, and MELD and D-MELD (donor age*MELD) scores were significantly higher in the SLKTx group. SLKTx had longer waiting list time (P = .0034) as well as higher surgical difficulty, testified by more blood transfusions (P = .0083), increased use of classic caval reconstruction (P = .0024), and more frequent need of abdominal packing for bleeding control (P = .0003). In addition, duration of hospital stay (P < .0001), second-look surgery (P = .0082), post-transplant dialysis (P < .0001), and post transplant infections (P = .04) were significantly greater in SLKTx group. Acute rejection episodes involving the liver were significantly less in SLKTx than in LTx (14% vs 41%; P = .0045). Liver graft and patient survival at 10 years after transplantation was similar in the 2 groups (liver graft: SLKTx, 80% vs LTx, 77% [P = .85]; patient: SLKTx, 86% vs LTx, 79% [P = .56]). CONCLUSIONS: Despite being technically challenging, SLKTx provided excellent long-term results and was shown to be an effective use of liver grafts. PMID- 26361667 TI - Intra-Operative Contrast Cholangiography in Living Donor Liver Transplantation: The ISMETT Experience. AB - BACKGROUND: We evaluated the clinical impact of donor biliary anatomy discrepancies (DBAD) achieved by comparing pre-operative evaluation obtained with magnetic resonance (MR)/magnetic resonance cholangiopancreatography (MRCP) imaging, with intra-operative cholangiography (IOC) on the living related liver donor (LDLT) and recipient. METHODS: This single-center, retrospective study included 97 consecutive adult-to-adult (A2A) LDLT performed in our hospital in the last 12 years. Donor sex and age, living donors with biliary and/or vascular anomalies, recipient age, sex, primary etiology, re-transplantation, Model of End Stage Liver Disease score, co-morbidities, arterial and biliary recipient complications assessed on the basis of clinical follow-up were collected and analyzed for significance through the use of a multivariate linear regression model. RESULTS: Biliary complications in the donor (DBC) were detected in 8 (8.2%) cases. Biliary complications in the recipients (RBC) were detected in 38 (39%) cases. DBADs were found in 32 (33%) cases and resulted strictly related to RBC (P = .05). CONCLUSIONS: After adjusting for co-variables, results of the linear regression analysis confirmed that DBAD is an independent predictor of RBC, but it is not significantly associated with vascular complications or patient survival. We showed that RBCs after LDLT were influenced by DBAD. PMID- 26361668 TI - Pulmonary Hypertension in Chronic Obstructive Pulmonary Disease and Pulmonary Fibrosis: Prevalence and Hemodynamic Differences in Lung Transplant Recipients at Transplant Center's Referral Time. AB - INTRODUCTION: Single or bilateral lung transplantation is a therapeutic procedure for end-stage lung diseases. In particular, in cases of chronic obstructive pulmonary disease (COPD) and pulmonary fibrosis, patients can be referred to the transplant center late and with important comorbilities. Pulmonary hypertension (PH) associated with lung diseases not only is an index of poor outcome but also is an indication for bilateral procedure. METHODS: We conducted a retrospective observational study. We analyzed right heart catheterization in a consecutive series of patients who underwent lung transplantation from 2006 to 2014 for end stage COPD and pulmonary fibrosis. RESULTS: We included in the study 73 patients (35 with fibrosis and 38 with COPD); prevalence of PH was higher in the COPD group (84.3% vs 31.4%), and with worse hemodynamic parameters (mean pulmonary artery pressure [30.3 mm Hg vs 24.1 mm Hg]). The majority of COPD patients presented mild or moderate PH, and fibrosis patients showed normal pulmonary arterial pressures. CONCLUSIONS: COPD patients are referred to the Transplant Center with a higher prevalence of PH because of an echocardiographic screening or a late referral, but many patients survive on the waiting list and undergo the procedure. On the other hand, patients transplanted with interstitial diseases have a lower prevalence of PH; this can be explained by an earlier referral or a higher mortality on the waiting list and a more aggressive and rapidly progressing disease. PMID- 26361670 TI - Pancreas Transplantation: Small-Center Experience in Type 1 Diabetes Mellitus in a High-Incidence Region. AB - BACKGROUND: Pancreas transplantation (PT) is the best option of care for patients with type I diabetes mellitus (T1DM). METHODS: From July 2005 to September 2014, we performed 27 PT from deceased donors (24 simultaneous pancreas-kidney transplantations [SPKT] and 3 pancreas transplantations alone) in a region with a high incidence of T1DM. RESULTS: Enteric drainage and systemic venous derivation were accomplished for all PT. Cold and warm ischemia times were 291 +/- 70 minutes and 32 +/- 9 minutes, respectively. The rate of early re-operations was 33%, mainly because of bleeding occurrence. Mean donor age was 31 +/- 11 years; all patients had ABO compatibility and negative cross-match. With a mean follow up time of 2.3 years, no death was registered. Graft survival of PT was 96.7%, with 1 graft loss in the SPKT group (3.7%) after acute rejection. Nine patients were submitted successfully to re-operation for no life-threatening complications within 30 post-operative days. No early or late episode of vascular thrombosis, pancreatitis, or pancreatic fistula was observed. All patients with a functioning graft had excellent metabolic control, with mean glycosylated hemoglobin level at last follow-up of 5.5% and median fasting glucose level of 95 +/- 13 mg/dL, comparable to that in the non-diabetic population. CONCLUSIONS: In our experience, PT is an excellent therapeutic solution for patients with T1DM. Despite fewer than 5 PT performed per year, graft and patient outcomes were similar to those in high-volume centers. PMID- 26361669 TI - Evaluation of Right Ventricular Function in the Management of Patients Referred for Left Ventricular Assist Device Therapy. AB - BACKGROUND: Speckle tracking echocardiography analysis (STE) has recently allowed an in-depth analysis of right ventricular (RV) performance. The aim of the study was to observe RV function by STE in patients with advanced heart failure before and after left ventricular assist device (LVAD) implantation. METHODS: A transthoracic echocardiogram was performed in 19 patients referred for LVAD implant at baseline and with serial echocardiograms after LVAD implantation (Jarvik 2000). All echocardiographic images were analyzed off line by an independent operator to calculate with STE the RV free wall longitudinal strain (RVLS). RESULTS: All the patients, except 4, showed a progressive increase of RVLS after LVAD implant. However, 4 patients, who presented the lowest RVLS values at baseline, presented a further RV failure in the postoperative. The value of -11% represented the empirical preoperative cutoff able to identify patients at greater risk of postimplant RV failure. CONCLUSIONS: RV myocardial deformation may have important clinical implications for the selection and management of LVAD patients. It can be used to evaluate RV function before LVAD implantation, to drive decisional strategy regarding the management of this type of patients, and after LVAD implant for the follow-up. PMID- 26361671 TI - Liver Regeneration Induced By Extracorporeal Portal Vein Arterialization in a Swine Model of Carbon Tetrachloride Intoxication. AB - INTRODUCTION: This study aimed to determine whether a controlled portal blood arterialization by a liver extracorporeal device (L.E.O2 NARDO) is effective in treating acute hepatic failure (AHF) induced in swine by carbon tetrachloride (CCl4) administration. MATERIALS AND METHODS: Sixteen swine with AHF induced by intraperitoneal injection of CCl4 in oil solution were randomly divided into 2 groups: animals that received L.E.O2 NARDO treatment 48 hours after the intoxication (study group; n = 8); and animals that were sham operated 48 hours after the intoxication (control group; n = 8). Blood was withdrawn from the iliac artery and reversed in the portal venous system by an interposed extracorporeal device. Each treatment lasted 6 hours. The survival was assessed at 5 days after L.E.O2 NARDO treatment or sham operation. In both groups blood samples were collected for biochemical analysis at different study time and liver biopsies were performed 48 hours after intoxication and at humane killing. RESULTS: In the study group decreased transaminases levels and a more rapid international normalized ratio (INR) recover were detected as compared with the control group. Six animals of the study group (75%) versus 1 animal (12.5%) of the control group survived at 5 days after surgery with a statistically significant difference (P < .05). Liver biopsies performed at humane killing showed damaged areas of the livers reduced in the study group compared with biopsies of the control group. CONCLUSIONS: Arterial blood supply in the portal system through the L.E.O2 NARDO device is easily applicable, efficacious, and safe in a swine model of AHF induced by CCl4 intoxication. PMID- 26361672 TI - Massive Retro-Pneumoperitoneum and Lower Limb Subcutaneous Emphysema After Pediatric Heart Transplantation: A Case Report. AB - An emphysema in a lower limb is usually a clinical sign of a severe and life threatening infection. We report a rare case of subcutaneous emphysema of the left lower limb associated with a massive retro-pneumoperitoneum and pneumatosis intestinalis after cardiac transplantation in a 4-year-old girl. The child was nearly asymptomatic beside an abdominal distension. A benign pneumoperitoneum associated with an extensive pneumatosis intestinalis is a rare complication after organ transplantation and should be treated conservatively. The association with an emphysema in a lower limb in a child has not been previously reported to our knowledge in the literature. PMID- 26361673 TI - Acute Liver Failure in an Adult, a Rare Complication of Alagille Syndrome: Case Report and Brief Review. AB - Alagille syndrome (AS) is an autosomal-dominant, multisystem disorder affecting the liver, heart, eyes, skeleton, and face. The manifestations are predominantly pediatric. Diagnosis is based on findings of a paucity of bile ducts on liver biopsy combined with >=3 of 5 major clinical criteria. Orthotopic liver transplantation (OLT) is the only option for treating patients who developed liver failure, portal hypertension, severe itching, and xanthomatosis. It is difficult to establish clear criteria for OLT; indications are controversial because of the wide variety of clinical symptoms and the multisystem involvement. Generally, AS-associated liver disease is never an acute illness. We report the case of a 28-year-old woman with AS who underwent urgent OLT for acute liver failure. At 24 months posttransplant, the patient is in good clinical condition and with normal hepatic and renal function. PMID- 26361675 TI - Gerundium: A Comprehensive Public Educational Program on Organ Donation and Transplantation and Civil Law in Hungary. AB - BACKGROUND: Organ transplantation has become an organized, routine, widely used method in the treatment of several end-stage diseases. Kidney transplantation means the best life-quality and longest life expectancy for patients with end stage renal diseases. Transplantation is the only available long-term medical treatment for patients with end-stage liver, heart, and lung diseases. Despite the number of transplantations increasing worldwide, the needs of the waiting lists remain below expectations. METHODS: One of the few methods to increase the number of transplantations is public education. In cooperation with the University of Debrecen Institute for Surgery Department of Transplantation, the Hungarian National Blood Transfusion Service Organ Coordination Office, and the Local Committee Debrecen of Hungarian Medical Students' International Relations Committee (HuMSIRC), the Gerundium, a new educational program, has been established to serve this target. Gerundium is a special program designed especially for youth education. Peer education means that age-related medical student volunteers educate their peers during interactive unofficial sessions. RESULTS: Volunteers were trained during specially designed training. Medical students were honored by HuMSIRC, depending on their activity on the basis of their own regulations. Uniform slides and brochures to share were designed. Every Hungarian secondary school was informed. The Local Committee Budapest of HuMSIRC also joined the program, which helps to expand our activity throughout Hungary. The aim of the program is public education to help disperse disapproval, if presented. CONCLUSIONS: As a multiple effect, our program promotes medical students to have better skills in the field of transplantation, presentation, and communication skills. Our program is a voluntary program with strong professional support and is free of charge for the community. PMID- 26361676 TI - Results of Expanded-Criteria Donor Kidneys: A Single-Center Experience in Hungary. AB - BACKGROUND: To ease organ shortage, many transplant centers accept kidneys from expanded-criteria donors (ECDs). Our aim was to analyze the results of ECD grafts in our center. METHODS: Data on cadaveric donors were retrospectively analyzed between January 2011 and September 2014. Definition of ECD was: (1) donor age >=60 years, (2) donor age 50 to 59 years, and (3) the presence of 2 among the following criteria: hypertension, serum creatinine >1.5 mg/dL, or death from cerebrovascular accident. Standard-criteria donors (SCDs) were those who did not meet the criteria for an ECD. RESULTS: During the observation period, 215 cadaveric donors were reported within our region, and 14 kidneys were offered to our center from Eurotransplant. Ninety-one (40%) among the reported donors were ECDs and 123 (54%) were SCDs. The rates of delayed graft function (DGF) and acute rejection (ARE) were not influenced by transplantation of an ECD graft. The cumulative patient and graft survival rates for ECDs were comparable with those of patients who received an optimal graft. CONCLUSIONS: ECD grafts can be transplanted safely, without the increased risk of DGF, ARE, and inferior patient and graft survival, in the case of careful patient allocation, and with the use of induction therapy. PMID- 26361677 TI - Cardiovascular Screening and Management Among Kidney Transplant Candidates in Hungary. AB - INTRODUCTION: Cardiovascular disease is a major cause of morbidity and mortality in end-stage renal disease patients on dialysis and the most common cause of death in the immediate post-transplantation period. The aim of our study was to describe a novel approach of cardiovascular screening and management of dialysis patients evaluated for the transplant waiting list. METHODS: Twenty-eight patients with end-stage renal disease put on the waiting list between July 2013 and July 2014 were subjected to a prespecified cardiovascular screening protocol utilizing noninvasive and/or invasive tests. Patients were subsequently divided into 3 strata in terms of their estimated cardiovascular risk. Each of these groups were then prescribed interventions aiming to improve their cardiovascular condition. RESULTS: According to our prespecified protocol of cardiovascular screening studies, 15 (54%) patients were identified as low, 5 (18%) as intermediate, and 8 (28%) as high risk. Four (14%) patients were current smokers. In the low-risk group, we initiated a patient education program involving counseling on regular exercise such as swimming or cycling to improve their functional capacity. In the high-risk group revascularization was done in 5 cases (63%), including 3 percutaneous transluminal coronary angioplasties (PTCA) with stents for single-vessel disease, and coronary artery bypass graft surgeries (CABG) for triple-vessel disease in 2 cases. In the medium-risk group medical management was opted for, including introduction of beta-blockers, inhibitors, statins, and ezetimibe, as well as efforts to optimize anemia management, indices of bone-mineral disease, and fluid status. CONCLUSION: In our regional transplant program, we introduced a comprehensive multidisciplinary approach to treat potential transplant candidates according to cardiovascular risk stratification based on a prespecified screening protocol. Further studies are needed to correlate this novel strategy with post-transplantation outcomes. PMID- 26361678 TI - Survey About the Cancer Risk of Renal Transplant Recipients. AB - INTRODUCTION: There is a greater risk of malignant tumors developing in kidney transplant patients. Due to this, early detection is of outmost importance, in which screening tests play an important role. METHODS: We have conducted a survey among renal transplant recipients to assess individual risk factors. RESULTS: Of 530 respondents, 55 developed post-transplantation tumors. Cutaneous tumors (36%) and kidney cancer (16%) were the most frequent. In total, 59% of recipients were over the age of 50, 61.7% were over the normal body-mass index range, 40.3% smoked or used to smoke, and 21.8% had diabetes. Five patients had hepatitis B virus and 11 were hepatitis C virus-positive. Malignancies developed significantly more frequent in men than in women (P = .04). The progressing of age (P = .0001) and the time elapsed after transplantation (P < .01) also were associated with a significant increase in the occurrence of post-transplantation tumors. CONCLUSION: We have created a database to facilitate a more personalized and efficient screening program for immunocompromised patients. PMID- 26361679 TI - Changes in Tumor Characteristics in Kidney Transplanted Patients Over the Last 40 Years. AB - BACKGROUND: Post-transplantation tumors (PTTs) are the greatest limiting factor for patient survival following organ transplantation. AIM: To describe the incidence and main characteristics of malignancies developed in patients who underwent kidney transplantation in Budapest between 1973 and 2014. METHODS: During this period, the essential data for PTTs were repeatedly evaluated. In this study, the results from 1990, 1995, 2000, 2006, and 2013 were evaluated. RESULTS: Incidence of PTTs increased from 2.3% to 11.1%. Male/female ratio was 2:1. Skin, native kidney, and lung cancers were the most common tumors during the entire observation period. Lymphoma was seen rarely at the beginning and became common in 2013. The same was observed in the most frequent general population tumors (colorectal, breast, hepatic, prostate, gastric cancer, and malignant melanoma) where the occurrence increased in the last 10 years. Mean age of patients increased from 35.7 to 56.5 years. During the last 20 years, age of recipients increased: above 50 years from 22.9% to 40.5%, and above 60 years from 8.2% to 23.1%. Patient survival was different according to tumor stage at discovering, i.e. renal cell carcinoma was usually discovered in stage I. resulting in a 66.1% 5-year survival rate, whereas 43.5% of colorectal cancers were diagnosed in stage IV, with a 13.9% 5-year survival rate. CONCLUSION: The frequency of PTTs and proportion of elderly persons undergoing transplants are continuously increasing. Tumor stage is a determining factor for patient survival. Recognition of precancerous conditions, diagnosis of tumors in early stage, and oncological screening can improve survival time. PMID- 26361680 TI - Examinations of Factors Influencing Survival of Liver Transplantation for Hepatocellular Carcinoma: A Single-Center Experience From Budapest. AB - INTRODUCTION: Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death worldwide. Orthotopic liver transplantation (OLT) is the best therapy of choice for early, unresectable HCC. The Hungarian Liver Transplantation Program was launched in 1995 at the Department of Transplantation and Surgery, Semmelweis University, Budapest. From that time more than 60 patients underwent OLT for hepatic tumors, which in most cases were HCC. Our clinical examination was undertaken to analyze the possible influential factors of outcomes for our series of patients who received OLT for HCC. METHODS: We performed a review of all patients who underwent OLT for HCC at our department from 1996 to October 1, 2013. Disease extent was determined by preoperative computed tomography or magnetic resonance images. All explants were examined and categorized based on tumor number, size, distribution, HCC histologic grade, and vascular invasion. Patients with HCC were classified as having tumors either meeting Milan criteria, beyond Milan criteria but within UCSF criteria, or exceeding UCSF criteria. OLT was performed using standard techniques including orthotopic implantation with cross-clamp technique or with the piggyback technique. Postoperative immunosuppression included a triple drug regimen of calcineurin inhibitor (CNI), mycophenolate mofetil (MMF), and prednisone. mTOR inhibitors have been available since 2004. RESULTS: HCC most commonly occurs in the presence of cirrhosis as a result of longstanding chronic liver disease. Most of our patients who underwent OLT for HCC are 56 to 60 years old, and most also had underlying HCV cirrhosis. As of October 1, 2013, 21 of 49 (42.85%) patients had died after OLT for HCC. The main cause was the recurrence of the HCC in 38%, followed by sepsis in 33%, and HCV recurrence in 19%. One death each (4.7% of the total number of deaths) was caused by primary nonfunction of the graft, acute myocardial infarct, and de novo malignancy, respectively. Overall survival for the entire group at 1, 3, and 5 years after transplantation was 73.48%, 65.2%, and 50.08%, respectively. Using pretransplant imaging, 34 tumors (69.3%) were within Milan criteria, 8 (16.3%) were beyond Milan but within UCSF criteria, and 7 (14.3%) exceeded UCSF criteria. Based on explant pathology, 30 tumors (61.2%) were within Milan criteria, 7 (14,3%) were beyond Milan but within UCSF criteria, and 12 (24.3%) exceeded UCSF criteria. New onset, non-HCC malignant tumor developed in 2 cases (4%). There was no significant difference between the surgical techniques or the immunosuppressive strategies. Using the Cox analysis in our series, it can be seen that mortality was higher with tumors exceeding Milan criteria but within UCSF criteria compared with tumors within Milan criteria (Coef. = 0.5749 in Setting 1 and 0.1226 in Setting 2), and even higher with tumors beyond UCSF criteria compared with tumors within Milan criteria (Coef. = 0.7228 in Setting 1 and 0.1456 in Setting 2). Recurrence of the tumor causes higher mortality (Coef. = 1.709 in Setting 1 and 1.0256 in Setting 2). It seems that using an mTOR inhibitor has a beneficial impact on mortality (Coef. = 1.409 in Setting 1). Vascular invasion was associated with higher mortality (Coef. = 0.6581in Setting 1). Higher AFP levels correlated with higher mortality but not significantly (Coef. = 0.0002 in Setting 2). In our series, survival after OLT for HCC was best with tumors within Milan criteria comparing those exceeded Milan criteria (odds ratio = 4.000). CONCLUSION: According to our findings, the Milan criteria are still the safest criteria system; however, slightly expanded criteria do not have significantly worse results. Preoperative imaging methods sometimes show fewer or smaller tumors, and the explant histology reports the exact staging of HCC at the time of OLT. Histological examination especially of the lymphovascular invasion is mandatory to assess the estimated prognosis. Extremely high levels of AFP mean higher risk. HCC recurrence is an important factor on the outcome; therefore, continuous oncologic screening is mandatory. Immunosuppressant agents are chiefly responsible not just for higher risk of recurrence but for higher risk to develop de novo malignancies. Viral serology must be done periodically to catch HCV recurrence in time and begin adequate antiviral therapy. Potentially, mTOR inhibitors could be potent immunosuppressive agents after OLT for HCC due to this antiproliferative effect. PMID- 26361681 TI - Analysis of Incretin Hormones After Orthotopic Liver Transplantation. AB - BACKGROUND: Several well-known risk factors play an important role in the development of new-onset diabetes mellitus after orthotopic liver transplantation (OLT). Immunosuppressant drugs and hepatitis C virus (HCV) infection have a direct effect on pancreatic beta cells resulting insulin hyposecretion. Steroids mainly cause peripheral insulin resistance. Although in type 2 diabetes mellitus the incretin-insulin axis is impaired and incretin hormones are advantageous targets of many antidiabetic drugs, the endocrinologic background of new-onset diabetes mellitus after transplantation (NODAT) is still not completely understood. METHODS: During the first postoperative year the oral glucose tolerance test (OGTT) was performed on 21 patients after OLT. Patients' glycemic metabolic status was determined according to the results of OGTT. The level of incretin hormones, namely glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), were measured with competitive enzyme-linked immunoassay reaction. RESULTS: Six patients had normal glucose tolerance (NGT), 9 had impaired glucose tolerance (IGT, serum glucose 7.8-11.0 mmol/L), and 6 were diagnosed with NODAT (serum glucose >11.1 mmol/L). Fasting insulin and c-peptide levels were higher if IGT/NODAT was found. Insulin secretion was not further stimulated after OGTT. GIP and GLP-1 levels did not differ significantly, not even after glucose load. HCV infection had not influenced the levels of incretin hormones [GLP-1 (0 min): 1.21 +/- 0.27 vs 1.38 +/- 0.65; P = ns; GLP-1 (120 min): 1.46 +/- 0.61 vs 1.07 +/- 0.58; P = ns; GIP (0 min): 2.55 +/- 0.95 vs 1.99 +/- 0.63; P = ns, GIP (120 min): 2.62 +/- 0.6 vs 2.33 +/- 0.77; P = ns]. CONCLUSION: The stimulation of insulin secretion in NODAT is limited. Incretin hormones are present independently from the current glycemic status. The use of dipeptidyl peptidase-4 inhibitors through their positive effect on the incretin-insulin axis can be beneficial in the therapy of NODAT after liver transplantation. PMID- 26361683 TI - Complete Remission of Post-transplantation Recurrence of Focal Segmental Glomerulosclerosis With the Use of Adrenocorticotrophic Hormone Gel: Case Report. AB - BACKGROUND: Post-transplantation recurrence of primary focal and segmental glomerulosclerosis (FSGS) is estimated to occur in 30%-50% of cases and doubles the risk of allograft failure. Treatment of recurrent FSGS is challenging because specific pathogenic targets are unknown and available therapeutic options have limited efficacy. CASE REPORT: We report a case of recurrent FSGS with nephrotic range proteinuria (urine protein creatinine ratio [UPCR], >50) and debilitating edema that was resistant to rituximab and plasmapheresis. The patient had a remarkable response to adrenocorticotropic hormone (ACTH) gel and achieved complete remission (UPCR, 0.5; serum albumin, 4.1 g/dL; serum creatinine, 1.0 mg/dL) which was maintained over 10 months on this treatment. CONCLUSIONS: We conclude that ACTH gel is a potential therapeutic option for post-transplantation recurrence of FSGS and warrants further evaluation. PMID- 26361682 TI - Ischemia/reperfusion-induced Kidney Injury in Heterozygous PACAP-deficient Mice. AB - Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide with very diverse distribution and functions. Among others, PACAP is a potent cytoprotective peptide due to its antiapoptotic, anti-inflammatory, and antioxidant actions. This also has been shown in different kidney pathologies, including ischemia/reperfusion-induced kidney injury. Similar protective effects of the endogenous PACAP are confirmed by the increased vulnerability of PACAP deficient mice to different harmful stimuli. Kidneys of homozygous PACAP deficient mice have more severe damages in renal ischemia/reperfusion and kidney cell cultures isolated from these mice show increased sensitivity to renal oxidative stress. In our present study we raised the question of whether the partial lack of the PACAP gene is also deleterious, i.e. whether heterozygous PACAP-deficient mice also display more severe damage after renal ischemia/reperfusion. Mice underwent 45 or 60 minutes of ischemia followed by 2 weeks reperfusion. Histological evaluation of the kidneys was performed and individual histopathological parameters were graded. Furthermore, we investigated apoptotic markers, cytokine expression, and the activity of superoxide dismutase (SOD) enzyme 24 hours after 60 minutes of renal ischemia/reperfusion. We found no difference between the intact kidneys of wild-type and heterozygous mice, but marked differences could be observed following ischemia/reperfusion. Heterozygous PACAP-deficient mice had more severe histological alterations, with significantly higher histopathological scores for most of the tested parameters. Higher level of the proapoptotic pp38 MAPK and of some proinflammatory cytokines, as well as lower activity of the antioxidant SOD could be found in these mice. In conclusion, the partial lack of the PACAP gene results in worse outcomes in cases of renal ischemia/reperfusion, confirming that PACAP functions as an endogenous protective factor in the kidney. PMID- 26361684 TI - Primary Graft Dysfunction After Zero-Mismatch Kidney Transplantation Secondary to Early Biopsy-Proven Acute Cell-Mediated Rejection: Case Report. AB - We report a case of primary renal allograft dysfunction and early acute cell mediated rejection after a 12/12 HLA antigen zero-mismatch (0MM) transplant. The recipient was a 40-year-old white man who was highly allosensitized, with a calculated panel reactive antibody score of 100%. In posteroperative day 1 the recipient remained anuric and underwent dialysis because of hyperkalemia. Graft biopsy showed early acute cellular rejection, Banff grade 2B. No evidence of antibody-mediated rejection was observed. To our knowledge, this case is the 1st to report early cell-mediated rejection after 12/12 HLA antigen 0MM kidney transplantation. This case suggests that highly sensitized candidates are at high immunologic risk even in the context of 0MM kidney transplantation. PMID- 26361685 TI - Myeloid Sarcoma Presenting With Multiple Skin and Subcutaneous Mass Without Leukemic Manifestations After Renal Transplantation. AB - BACKGROUND: Myeloid sarcoma is well described and known in clinical practice, however, it is a rare condition after receiving renal transplantation. Immunosuppressive therapy is thought to be the main cause in these cases. CASE REPORT: A 45-year-old woman accepted a right kidney transplantation because of her chronic renal insufficiency and uremia in May 2011. She had to receive a left kidney transplantation again in February 2012 because she had renal failure again after receiving the right kidney transplantation. She received immune inhibitors treatment. After the latter operation, her renal function was normal. The third operation was done to remove the right transplanted kidney in July 2012. The diagnosis of the kidney was myeloid sarcoma. The blood and bone marrow biopsy had no evidence of leukemia. She then received chemotherapy. There was a small skin nodule on the left arm of approximately 0.5 cm in August 2012; after that its diameter enlarged progressively to about 5 cm and more nodules and masses gradually appeared on her face, arms, trunk, lower limbs, and feet over the course of 1 year. The skin biopsy specimen obtained from her left arm showed myeloid sarcoma too. She was admitted to the Orthopedics Department for severe pain and swelling in the left foot in September 2014 and underwent an operation for resecting the mass in the left foot. Pain was apparently alleviated and the incision healed well. CONCLUSIONS: The patient is still alive with no evidence of leukemia after a 30-month follow-up. PMID- 26361686 TI - A Successful Renal Transplantation Case After Stem Cell Transplantation. AB - Renal transplantation is the most effective treatment method for end-stage renal disease (ESRD). However, new treatment modalities are being investigated, such as immunotoleration, to avoid the acute and chronic side effects of immunosuppressant drugs. We report a case in which a man had undergone allogenic stem cell transplantation from his brother 16 years ago due to chronic myeloid leukemia, and who then developed ESRD due to arterial hypertension and underwent renal transplantation (Rtx) from the same brother. The patient was followed up without immunosuppression due to full chimerism. PMID- 26361687 TI - Central Serous Chorioretinopathy: Signal to Reduce Corticoid in Renal Transplant Recipients? AB - OBJECTIVE: The aim of this work was to report the treatment effectiveness of central serous chorioretinopathy (CSCR) in a renal transplant recipient who received conventional therapy with little effect, and then reducing corticoid successively and with a better outcome later. METHODS: We performed a retrospective comparison of best-corrected visual acuity (BCVA) and spectral domain optical coherence tomography (SD-OCT) of a 57-year-old renal transplant recipient who received conventional therapy and reducing corticoid successively after he was diagnosed as CSCR in the left eye. RESULTS: The BCVA of the left eye stayed at 20/200 after 3 months' conventional therapy, but rapidly improved to 20/25 after reducing corticoid by one-half. At the same time, SD-OCT showed much more obvious absorption of retinal liquid in the left eye from reducing corticoid than from conventional therapy. Despite the reducing of corticoid by one-half, the patient did not show any signs of rejection of the renal transplant. CONCLUSIONS: CSCR may be a sign in renal transplant recipients for reducing corticoid, and reducing corticoid might be a more reliable and safer treatment for such patients. PMID- 26361689 TI - A Rare Cause of Diarrhea in a Kidney Transplant Recipient: Dipylidium caninum. AB - We report the first case of dipylidiasis in a kidney transplant recipient. Watery diarrhea due to Dipylidium caninum was observed in a male patient who had been undergone kidney transplantation 2 years before. The patient was successfully treated with niclosamide. D. caninum should be considered as an agent of diarrhea in transplant patients. PMID- 26361688 TI - Case Report: Hemolytic Anemia Following Deceased Donor Renal Transplantation Associated With Tranexamic Acid Administration for Disseminated Intravascular Coagulation. AB - BACKGROUND: Long-term outcomes of kidney transplantation with organs from donors with disseminated intravascular coagulation (DIC) are comparable with those from other deceased donors. The use of tranexamic acid to impair fibrinolysis in the treatment of DIC is becoming increasingly frequent, particularly in the trauma setting. However, the effects of tranexamic acid on a transplanted kidney allograft are unknown. RESULTS: We report 2 cases of kidney transplantation following administration of tranexamic acid to the donor prior to organ donation. Microthrombi were present in the renal allografts. Both recipients experienced clinically significant hemolytic anemia, which typically occurs at a very low frequency. CONCLUSIONS: These cases illustrate a potential concern for the use of tranexamic acid in deceased kidney donors with DIC. PMID- 26361690 TI - Cat-Scratch Disease: Case Report and Review of the Literature. AB - Cat-scratch disease (CSD) is caused by Bartonella henselae and characterized by self-limited fever and granulomatous lymphadenopathy. In some cases signs of a visceral, neurologic, and ocular involvement can also be encountered. In this report we describe the development of CSD in a kidney transplant patient. Immunocompromised hosts are more susceptible to infection from Bartonella compared with the standard population. Infection of Bartonella should be considered as a differential diagnosis in kidney transplant patients with lymphadenopathy of unknown origin. PMID- 26361692 TI - Gromerulocystic Kidney Disease in a Transplanted Kidney: Case Report. AB - The patient was a 28-year-old man with chronic kidney disease in stage 5 and in the course of chronic membranoroliferative glomerulonephritis. The patient was treated for a period of 2 months using peritoneal dialysis. In September 2014, he had a kidney transplant from a deceased donor. Four months after transplantation the patient was admitted to the hospital for a protocol biopsy. His creatinine was 1.5 mg/dL and urea was 59 mg/dL, urinalysis was normal in blood count with a normocytic anemia-hemoglobin level of 7.8 mmol/L. We obtained a histopathological evaluation of the cortex and medulla of the kidney. Glomeruli dilatation of Bowman space with reduced glomerular capillary tufts was found in the section. Histopathological evaluation indicated gromerulocystic kidney disease in a transplanted kidney. PMID- 26361691 TI - Colovesical Fistula After Renal Transplantation: Case Report. AB - Colovesical fistula is a relatively rare condition that is primarily related to diverticular disease. There are few reports of colovesical fistula after renal transplantation. We report of a 53-year-old man who was diagnosed with colovesical fistula after recurrent urinary tract infection, 5 months after undergoing cadaveric renal transplantation. Laparoscopic partial resection of the sigmoid colon with the use of the Hartmann procedure was performed. Six months after that surgery, there was no evidence of recurrent urinary tract infection and the patient's renal graft function was preserved. Physicians should keep colovesical fistula in mind as a cause of recurrent urinary tract infection in renal transplant recipients, especially in those with a history of diverticular disease. PMID- 26361693 TI - Case Report: Successful Living Donor Kidney Transplantation in a Highly Human Leukocyte Antigen-Sensitized Recipient With a Positive Cytotoxic Crossmatch Using Bortezomib-Based Desensitization Without Intravenous Immunoglobulin. AB - BACKGROUND: Highly sensitized patients, who produce antibodies against multiple anti-human leukocyte antigens, have significantly reduced chances for renal transplantation. Traditionally, desensitization protocols to reduce the levels of antibodies have relied on the use of intravenous immunoglobulin and plasmapheresis. RESULTS: Here we report the case of a patient with a calculated panel-reactive antibody level of 100% who was desensitized using multiple courses of bortezomib, a proteasome inhibitor, in an intravenous immunoglobulin-free regimen. The patient underwent a successful transplantation with an allograft from a living donor and has continued to do well post-transplantation. CONCLUSIONS: The expression of anti-human leukocyte antigen antibodies decreases the likelihood of transplantation for patients by restricting the available donor pool. New protocols that reduce antibody expression in these patients and allow for renal transplantation are needed. Bortezomib, as used in the patient reported here, represents a promising new medication for successful desensitization and transplantation. PMID- 26361694 TI - Thrombotic Microangiopathy as a Cause of Chronic Kidney Transplant Dysfunction: Case Report Demonstrating Successful Treatment with Eculizumab. AB - Atypical hemolytic uremic syndrome is a rare disease associated with genetic or acquired defects in complement regulation which frequently leads to renal failure. Disease often recurs early after kidney transplantation, leading to a rapid irreversible loss of function. Extrarenal features, such as hemolysis and thrombocytopenia, may not always occur, and diagnosis is made by demonstrating the classic features of thrombotic microangiopathy on renal biopsy. Eculizumab, a terminal complement inhibitor, has been used successfully to treat fulminant early recurrent disease after transplantation. We describe a case of disease recurrence presenting in the second year after transplantation with a gradual decline in function and the first report of eculizumab treatment for chronic thrombotic microangiopathy in a transplanted kidney. The resultant diagnostic challenges and successful response to eculizumab in this setting are discussed. PMID- 26361695 TI - Satisfactory Usage of a Lacerated Kidney for Transplantation: A Case Report. AB - BACKGROUND: Organ shortage is the main bottleneck in the wait-list for transplantation; therefore, expanding the donor pool is an effective way to solve the problem. Usage of the traumatized liver for transplantation has been applied, but the use of lacerated kidneys for transplant donor is rarely reported. METHODS: We reported a successful case of donation after brain death. The donor committed suicide by jumping from a campus dormitory building. One of the donated kidneys was severely injured. Two lacerations measured 4 * 1 * 1 cm in the medial margin of the graft and 1 * 1 * 1.5 cm in the front side of the graft, respectively. After repair with continuous absorbable suture, the lacerated kidney was transplanted to a recipient. RESULTS: The post-transplantation renal function gradually recovered. Furthermore, serious complications, such as large amounts of hemorrhage, delayed graft function, or urinary fistula did not occur. The serum creatinine dropped from 1232 MUmol/L to 120 MUmol/L and maintained normal range after surgery. In addition, the daily urine output was normal. At day 12 after operation, the patient was discharged. CONCLUSIONS: Our case shows that the use of a lacerated donor kidney appears to be feasible, but long-term effects need further observation. PMID- 26361696 TI - Laparoscopic Bilateral Nephro-Ureterectomy Approach for Complete Urinary Tract Extirpation for the Treatment of Multifocal Urothelial Carcinoma in a Kidney Transplant Patient: A Case Report and Literature Review. AB - BACKGROUND: Urothelial carcinoma of the transitional epithelium is the most common malignancy in the Thai kidney transplant population. METHODS: We report our experience in managing simultaneous upper and lower urinary tract urothelial cancer in a post-kidney transplant recipient through the use of laparoscopic bilateral nephron-ureterectomy and anterior pelvic exenteration with the use of a Studer orthotopic neobladder. A 35-year-old woman with end-stage renal disease underwent living related kidney transplantation in 2009. She presented with gross hematuria 5 years later. Enhanced computer tomography revealed diffuse bladder wall thickening with an intravesical polypoid soft tissue mass at the right ureterovesical junction extending to the right distal ureter. Hydronephrosis of the left native kidney without any demonstrable cause of obstruction was also noted. On trans-urethral resection, the pathological finding was high-grade, non invasive urothelial cell carcinoma. RESULTS: The operation was successfully performed without intra- or post-operative complications. The patient could ambulate independently on post-operative day 2. The kidney graft function did not change from her pre-operative baseline. At 6 months' follow-up, the patient had no tumor recurrence, returned to normal activities, and was able to void spontaneously without any need of intermittent catheterization. CONCLUSIONS: Laparoscopic bilateral nephron-ureterectomy for complete urinary tract extirpation is feasible, safe, and associated with low morbidity. This technique avoids a large abdominal midline incision or a bilateral flank incision for nephron-ureterectomy and is a good alternative surgical technique in post-kidney transplant patients who require complete urinary tract extirpation. PMID- 26361697 TI - Formation of Collateral Veins in a Graft Pancreas After a Simultaneous Pancreas and Kidney Transplantation: A Case Report. AB - A graft vein thrombosis is the main cause of early graft failure after pancreas transplantation. We report a case of formation of collateral veins in a graft pancreas after transplant. A 30-year-old woman underwent simultaneous pancreas and kidney transplantation. She was discharged 16 days after the operation with good pancreas and kidney function. A total occlusion of the portal vein was discovered on computed tomography (CT) performed at an outpatient clinic. She had no symptoms or signs of hyperglycemia. Venography was attempted for vein thrombectomy but failed. After 2 weeks of heparinization therapy, the edema disappeared and perfusion of the graft pancreas improved. However, the thrombotic occlusion was not resolved on CT. Arteriography of the Y-graft revealed collateral veins. She was discharged with warfarin. She is currently doing well without any symptoms or signs. This is the first reported case of collateral vein formation in a grafted pancreas after pancreas transplantation. PMID- 26361699 TI - Recurrence of Liver Transplantation Combined With Lung and Diaphragm Resection for Alveolar Echinococcosis: A Case Report. AB - Liver transplantation (LT) for alveolar echinococcosis (AE) with multiple-organ involvement is controversial. We report on a 31-year-old female patient suffering from AE with liver, lung, and diaphragm involvement. After an "extended" resection (liver, lung, and diaphragm were performed) combined with LT, recurrence still occurred after 6 years and the patient presented with hemoptysis. Puncture, aspiration, injection, reaspiration, and drainage (PAIRD) were performed and the effect was instantaneous. To our knowledge, no such surgical strategy for AE has previously been reported. In spite of the high risk of recurrence, choosing this surgical method is acceptable for a fatal AE and the recurrence could be controlled. PMID- 26361698 TI - Living-Donor Liver Transplantation for Hepatic Metastasis From Meningeal Hemangiopericytoma: A Case Report. AB - We report the case of a 58-year-old man referred to our hospital for liver tumor treatment. The patient had a history of neurosurgery for a meningeal hemangiopericytoma 16 years previously. Pre-operative imaging revealed a hypervascular tumor extending from Couinaud segment 4 to segment 8 of the liver, measuring 95 mm in diameter, indicating an atypical hepatocellular carcinoma. Because right trisectionectomy of the liver was considered to be high risk, living-donor liver transplantation (LDLT) was indicated. After transcatheter arterial embolization, LDLT was performed with the use of a left-lobe liver graft from the patient's son. Post-operative histological findings of the liver tumor were identical to those for meningeal hemangiopericytoma, therefore the patient was diagnosed with meningeal hemangiopericytoma that had metastasized to the liver. After LDLT, the patient had a healthy, active life for 2 years; then, a subcutaneous relapse was discovered in the left chest. The patient did not undergo any systemic chemotherapy in response to the relapse. After thoracic and orthopedic surgeries and radiotherapy for multiple metastases, the patient died 5 years and 5 months after LDLT. LDLT could be an effective treatment for localized metastatic hemangiopericytoma in the liver, but it should be indicated only for carefully selected patients. PMID- 26361700 TI - Liver Transplantation for Budd-Chiari Syndrome With Large Solitary Focal Nodular Hyperplasia of the Liver in a Patient With Essential Thrombocythemia: Case Report. [Corrected]. AB - Budd-Chiari syndrome is a rare condition caused by interrupted hepatic venous outflow in the hepatic veins, inferior vena cava, or right atrium. Reports from the literature have delineated on focal nodular hyperplasia (FNH)-like lesions in association with Budd-Chiari Syndrome. To our knowledge, there are no reports about true FNH lesions in patients with Budd-Chiari Syndrome. Focal nodular hyperplasia develops in disorders with aberrant circulation and vasculature. We report a case of Budd-Chiari syndrome in association with large solitary FNH in a 22-year-old man who was referred to our institution with sudden intermittent right upper quadrant abdominal pain, vomiting, diarrhea with pale stool, decreased appetite, dark urine, and abdominal distention for 15 days. Laboratory investigations revealed anemia, thrombocytosis, and abnormal liver function tests and coagulation profile. Imaging revealed hepatic vein thrombosis, confirming Budd-Chiari syndrome, and a 6.2 * 6.1 * 6.8 cm lesion in segment 8 of the liver. Primary cause of Budd-Chiari syndrome was essential thrombocythemia according to bone marrow biopsy and molecular testing results. The patient was treated medically and underwent transjugular intrahepatic portosystemic shunt insertion. The lesion in segment 8 continued to enlarge. Cadaveric liver transplantation was carried out. On gross and histologic examination of the explanted liver, the lesion was found to be a true FNH. PMID- 26361701 TI - Post-transplant Lymphoproliferative Disorders: A Rare Case of Primary Pericardial Involvement Epstein-Barr Virus-Correlated in Heart Transplantation. AB - Post-transplant lymphoproliferative disorders (PTLDs) are considered a fatal consequence of immunosuppression. We report a case of a 52-year-old patient, who underwent a cardiac transplantation and presented undefined recurrent episodes of pleuropericardial effusions without lymphoadenomegaly at chest radiographs and computed tomography. Histopathological analysis of the bioptic pericardium showed a specific chronic inflammation. Monitoring endomyocardial biopsies (EMBs) showed only 1 episodes of greater than grade 2R acute cellular rejection requiring immunosuppressive treatment, mild vasculitis in 2 subsequently EMBs while constantly negative for antibody-mediated rejection or infection. Only a post mortem examination demonstrated the presence of an aggressive acute non-Epstein Barr virus (EBV)-related proliferative disorder with unusual primitive localization into the pericardium and with coronary epicardial and intramyocardial necrotizing vasculitis and superimposed occlusive and subocclusive thrombosis. Recurrence of unexplained early pleuropericardial effusion and mild intramyocardial vasculitis should raise the suspicion of PTLD requiring reduction of immunosuppression, even in the setting of negative intramyocardial cellular infiltrate and tissue EBV-negative molecular assessment. PMID- 26361702 TI - Total Artificial Heart Bridge to Transplantation for a Patient With Occult Intracardiac Malignancy: Case Report. AB - Malignancy is the leading cause of long-term morbidity and mortality after heart and other solid organ transplantation; therefore, great emphasis is placed on pre and post-transplantation cancer screening. Even with meticulous screening during evaluation for heart transplant candidacy, an occult cancer may not be apparent. Here, we share the case of a 51-year-old man with refractory heart failure who underwent total artificial heart implantation as a bridge to transplantation with the surprise finding of an isolated deposit of metastatic carcinoid tumor nested within a left ventricular papillary muscle in his explanted heart. The primary ileal carcinoid tumor was identified and resected completely. After remaining cancer-free for 14 months, he was listed for heart transplantation and was transplanted 2 months later. He is currently 3.5 months out from heart transplantation and doing well, without evidence of recurring malignancy. PMID- 26361703 TI - Successful Treatment of Chronic Hepatitis C Infection With Direct-Acting Antivirals in a Heart Transplant Recipient: A Case Report. AB - BACKGROUND: Heart transplant (HT) recipients with chronic hepatitis C virus (HCV) infection are noted to have higher rates of HCV related morbidity and mortality. Treatment of HCV in the past was fraught with low cure rates, increased risk of graft rejection, and medication-related side effects. CASE REPORT: We report a case of successful treatment of HCV infection in a HT recipient. The patient was found to have HCV during his pretransplant workup. He underwent uneventful orthotopic HT in 2000. The HCV infection was monitored with regular liver enzymes and the surveillance liver biopsies at 2 and 5 years after HT showed mild but stable liver disease, and he stayed on chronic immunosuppression. He was not offered interferon-based HCV therapy because of the risk of steroid-resistant graft failure and cardiac decompensation. With the availability of the new direct acting antivirals (DAA) for HCV infection, and worsening of liver fibrosis on noninvasive testing, we treated him with sofosbuvir and simeprevir for 12 weeks. During treatment, he remained clinically stable from a cardiac standpoint and he showed biochemical improvement in his liver and renal functions. Tacrolimus levels remained stable and did not require any dose adjustment. He showed rapid virologic response and subsequently achieved sustained virologic response at 12 weeks. CONCLUSION: DAA use was safe and effective in treating HCV infection in a HT recipient. PMID- 26361704 TI - A Successful Second Stem Cell Transplantation in Fanconi Anemia: A Case Report. AB - OBJECTIVE: The aim was to describe a case of successful second stem cell transplantation in Fanconi anemia (FA). METHODS: A 7.5-year-old boy with FA was admitted for stem cell transplantation. The first matched sibling allogeneic bone marrow transplantation was done in January 2005. Until August 2008, the patient's blood count had been decreasing and the patient depended on transfusions, and anti-A Ab was detected (donor blood GP is A RH+). Therefore, the second matched sibling allogeneic peripheral blood stem cell transplantation was performed on November 27, 2008 with anti-thymocyte globulin alone as a second transplant conditioning. RESULT: The child has been disease-free for 5 years. CONCLUSION: Anti-thymocyte globulin alone as a second transplant conditioning may give first transplant failure FA patients the opportunity for a long-term disease-free survival. PMID- 26361705 TI - Early Post-transplant Lymphoproliferative Disease in the Donor Ureter Without Systemic Involvement: A Case Report. AB - BACKGROUND: Post-transplant lymphoproliferative disease is a serious complication of renal transplantation. Major risk factors include Epstein-Barr virus (EBV) seronegativity and induction immunosuppression with lymphocyte-depleting agents. RESULTS: We present a case of a 50-year year-old woman with very early onset PTLD confined to the donor ureter. Phenotypic studies on the tumor material reveal that the lymphoma was most likely of donor origin. A complete staging workup including the kidney allograft was negative for any other sites of involvement. CONCLUSIONS: This case, which had a fatal outcome, emphasizes the risk of renal transplantation in BV-negative individuals when given induction with lymphocyte depleting drugs. PMID- 26361706 TI - [Tricuspid vegetation giant in the context of infectious endocarditis caused by Staphylococcus aureus after an abortion]. PMID- 26361707 TI - [Left ventricular longitudinal systolic strain in children with history of Kawasaki disease]. AB - OBJECTIVE: Kawasaki disease (KD) is a systemic vasculitis that affects young children. Coronary artery aneurisms, ectasia and stenosis are its main complications and may lead to ischemic heart disease or sudden death. Echocardiography evaluation it's mandatory in all patients with history of KD. Left ventricular longitudinal systolic strain (LVLSS) measured by speckle tracking it's an accurate tool to evaluate global and segmental left ventricle mechanics. Clinical utility of LVLSS in children with KD hasn't been established. The goal of this study was to analyse if the presence of coronary lesions alters segmental LVLSS and if there is a relationship with the affected coronary territory. METHOD: Case series. A complete transthoracic echocardiography with LVLSS was performed in children with history of KD with at least 6 months after the acute phase. RESULTS: Nine patients where studied, with a median age of 6 years (minimum 2 and maximum 17). A percentage of 56 were male, and 77% had coronary aneurisms. An abnormal LVLSS was found in 56% of the population studied. All of the patients that had an abnormal LVLSS had coronary aneurisms with stenosis or complete occlusion confirmed by invasive coronary angiography and abnormal Nuclear Medicine perfusion scans. CONCLUSIONS: On the population studied, all patients with an abnormal LVLSS had obstructive coronary lesions and ischemic heart disease. PMID- 26361708 TI - Chronicles of foam films. AB - The history of the scientific research on foam films, traditionally known as soap films, dates back to as early as the late 17th century when Boyle and Hooke paid special attention to the colours of soap bubbles. Their inspiration was transferred to Newton, who began systematic study of the science of foam films. Over the next centuries, a number of scientists dealt with the open questions of the drainage, stability and thickness of foam films. The significant contributions of Plateau and Gibbs in the middle/late 19th century are particularly recognized. After the "colours" method of Newton, Reinold and Rucker as well as Johhonnot developed optical methods for measuring the thickness of the thinner "non-colour" films (first order black) that are still in use today. At the beginning of the 20th century, various aspects of the foam film science were elucidated by the works of Dewar and Perrin and later by Mysels. Undoubtedly, the introduction of the disjoining pressure by Derjaguin and the manifestation of the DLVO theory in describing the film stability are considered as milestones in the theoretical development of foam films. The study of foam films gained momentum with the introduction of the microscopic foam film methodology by Scheludko and Exerowa, which is widely used today. This historical perspective serves as a guide through the chronological development of knowledge on foam films achieved over several centuries. PMID- 26361709 TI - Blood-meal identification in phlebotomine sand flies (Diptera: Psychodidae) from Valle Hermoso, a high prevalence zone for cutaneous leishmaniasis in Ecuador. AB - Cutaneous leishmaniasis is a neglected tropical disease transmitted by phlebotomine sand flies of the genus Lutzomyia. In South America, cutaneous leishmaniasis is endemic in the majority of countries. There are no previous reports of phlebotomine sand fly host feeding sources in Ecuador. We identified blood meal sources for phlebotomine sand fly species in Valle Hermoso, a hyper endemic area for leishmaniasis in Ecuador. Phlebotomine sand fly collections were carried out during the dry and rainy seasons. PCR and multiplex PCR were performed from DNA extracted from the abdomens of blood-fed females to specifically identify the avian and mammalian blood meal sources. Avian-blood (77%), mammalian-blood (16%) and mixed avian-mammalian blood (7%) were found in the samples. At the species level, blood from chickens (35.5%), humans (2.8%), cows (2.8%) and dogs (1.9%) was specifically detected. Nyssomyia trapidoi was the most common species of Lutzomyia found that fed on birds. The present results may aid the development of effective strategies to control leishmaniasis in Ecuador. PMID- 26361710 TI - Multicenter evaluation of the Verigene Gram-negative blood culture nucleic acid test for rapid detection of bacteria and resistance determinants in positive blood cultures. AB - The Verigene Gram-Negative Blood Culture Nucleic Acid Test (BC-GN) is a microarray-based assay that enables rapid detection of 9 common Gram-negative bacteria and 6 resistance determinants directly from positive blood cultures. We compared the performance of BC-GN with currently used automated systems, testing 141 clinical blood cultures and 205 spiked blood cultures. For identification of BC-GN target organisms in clinical and spiked blood cultures, the BC-GN assay showed 98.5% (130/132) and 98.9% (182/184) concordance, respectively. Of 140 resistance genes positively detected in clinical and spiked blood cultures with the BC-GN test, 139 (99.3%) were confirmed by PCR, and the detection results were consistent with the resistance phenotypes observed. The BC-GN assay, thus, can potentially improve care for sepsis patients by enabling timely detection and targeted antimicrobial therapy. PMID- 26361711 TI - Trends in cannabis-related ambulance presentations from 2000 to 2013 in Melbourne, Australia. AB - AIMS: The current burden of cannabis-related presentations to emergency health services is largely unknown. This paper presents data collected over a 13-year period in metropolitan Melbourne, Australia as part of the Ambo Project, a unique surveillance system that analyses and codes paramedic records for drug-related trends and harms. METHODS: Cannabis-related ambulance attendances involving 15-59 year olds in metropolitan Melbourne were analysed retrospectively from 2000 to 2013 (n=10,531). Trends and attendance characteristics were compared among cannabis only (CO)-, cannabis and alcohol (CA)- and cannabis with polydrug use (CP)-related attendances. Changes in alcohol and drug involvements in cannabis related attendances were explored. RESULTS: Rates of cannabis-related ambulance attendances increased significantly over the study period. Increasing rate of attendances per 100,000 population per year changed from 0.6 (2000-2010) to 5.5 (2010-2013). This sharp change was driven by CO- and CP-related attendances (rate of CA-related attendance increased steadily). The highest increasing rate (15.6) was for CO-related attendances among 15-29 years old males (2010-2013). Crystal methamphetamine became the most common illicit co-intoxicant amongst cannabis presentations in 2013. CONCLUSIONS: Relative to the total drug-related burden on ambulance services, cannabis-related presentations appear to be a small but significant and increasing problem. Significant changes in trends across other drug involvement and demographic subgroups suggest a possible shift in the cannabis using population and/or a change in using behaviours. Public health strategies should raise awareness of the increased risk posed by cannabis polydrug use and high attendance subpopulations should be determined. PMID- 26361712 TI - Quantifying crime associated with drug use among a large cohort of sanctioned offenders in England and Wales. AB - AIM: To assess the relationship between testing positive for opiates and/or cocaine and prior offending. METHODS: 139,925 persons (107,573 men) identified from a saliva test for opiate and cocaine metabolites following arrest in England and Wales, 1 April 2005-31 March 2009, were case-linked with 2-year recorded offending history. The prior offending rate, accounting for estimated incarceration periods, was calculated by: drug-test outcome; gender; four main crime categories (acquisitive, non-acquisitive, serious acquisitive, and non serious acquisitive) and 16 sub-categories. Rate ratio (RR) compared opiate and/or cocaine positive to dual-negative testers. Adjusted rate ratio (aRR) controlled for age at drug test. RESULTS: The relationship between testing positive for opiates and cocaine and prior 2-year offending was greater for women than men (aRR men 1.77; 95% CI: 1.75-1.79: women 3.51; 3.45-3.58). The association was weaker for those testing positive for opiates only (aRR: men: 1.66, 1.64-1.68; women 2.73, 2.66-2.80). Men testing positive for cocaine only had a lower rate of prior offending (aRR: 0.93, 0.92-0.94), women had a higher rate (aRR: 1.69, 1.64-1.74). The strongest associations were for non-serious acquisitive crimes (e.g. dually-positive: prostitution (women-only): aRR 24.9, 20.9-29.7; shoplifting: aRR men 4.05, 3.95-4.16; women 6.16, 5.92-6.41). Testing positive for opiates and cocaine was associated with violent offences among women (aRR: 1.54, 1.40-1.69) but not men (aRR: 0.98, 0.93-1.02). CONCLUSIONS: Among drug-tested offenders, opiate use is associated with elevated prior offending and the association is stronger for women than men. Cocaine use is associated with prior offending only among women. PMID- 26361713 TI - Effects of 7-day continuous D-amphetamine, methylphenidate, and cocaine treatment on choice between methamphetamine and food in male rhesus monkeys. AB - BACKGROUND: Methamphetamine addiction is a significant public health problem for which no Food and Drug Administration-approved pharmacotherapies exist. Preclinical drug vs. food choice procedures have been predictive of clinical medication efficacy in the treatment of opioid and cocaine addiction. Whether preclinical choice procedures are predictive of candidate medication effects for other abused drugs, such as methamphetamine, remains unclear. The present study aim was to determine continuous 7-day treatment effects with the monoamine releaser d-amphetamine and the monoamine uptake inhibitor methylphenidate on methamphetamine vs. food choice. In addition, 7-day cocaine treatment effects were also examined. METHODS: Behavior was maintained under a concurrent schedule of food delivery (1-g pellets, fixed-ratio 100 schedule) and methamphetamine injections (0-0.32mg/kg/injection, fixed-ratio 10 schedule) in male rhesus monkeys (n=4). Methamphetamine choice dose-effect functions were determined daily before and during 7-day periods of continuous intravenous treatment with d amphetamine (0.01-0.1mg/kg/h), methylphenidate (0.032-0.32mg/kg/h), or cocaine (0.1-0.32mg/kg/h). RESULTS: During saline treatment, increasing methamphetamine doses resulted in a corresponding increase in methamphetamine vs. food choice. Continuous 7-day treatments with d-amphetamine, methylphenidate or cocaine did not significantly attenuate methamphetamine vs. food choice up to doses that decreased rates of operant responding. However, 0.1mg/kg/h d-amphetamine did eliminate methamphetamine choice in two monkeys. CONCLUSIONS: The present subchronic treatment results support the utility of preclinical methamphetamine choice to evaluate candidate medications for methamphetamine addiction. Furthermore, these results confirm and extend previous results demonstrating differential pharmacological mechanisms between cocaine choice and methamphetamine choice. PMID- 26361714 TI - Past 15-year trends in adolescent marijuana use: Differences by race/ethnicity and sex. AB - BACKGROUND: The potential for increases in adolescent marijuana use is an important concern given recent changes in marijuana policy. The purpose of this study was to estimate trends in marijuana use from 1999 to 2013 among a national sample of US high school students. We examine changes over time by race/ethnicity and sex. METHODS: Data are from the National Youth Risk Behavior Survey (YRBS), which involves biennial, school-based surveys that generate nationally representative data about 9th-12th grade students in the United States. Students self-reported sex, race/ethnicity, and marijuana use (i.e., lifetime use, past 30 day use, any use before age 13). We generated national estimates of the prevalence of marijuana use for the time period, and also tested for linear and quadratic trends (n=115,379). RESULTS: The prevalence of lifetime marijuana use decreased modestly from 1999 to 2009 (44% to 37%), and has increased slightly since 2009 (41%). Other marijuana use variables (e.g., past 30-day use) followed a similar pattern over time. The prevalence of past 30-day use from 1999 to 2013 for all groups and both sexes was 22.5%, and it was lowest among Asians and highest among American Indian/Alaska Natives. Although boys have historically had a higher prevalence of marijuana use, results indicate that male-female differences in marijuana use decreased over time. CONCLUSION: Despite considerable changes in state marijuana policies over the past 15 years, marijuana use among high school students has largely declined. Continued surveillance is needed to assess the impact of policy changes on adolescent marijuana use. PMID- 26361715 TI - Effects of acute ethanol exposure on class I HDACs family enzymes in wild-type and BDNF(+/-) mice. AB - BACKGROUND: Alterations of brain-derived neurotrophic factor (BDNF) have been associated with the development of addiction to different drugs of abuse, including ethanol (EtOH). EtOH exposure activates the BDNF-signaling cascade in dorsal striatum, which in turn affects further EtOH intake. Different alcohol exposures have been widely demonstrated to modulate chromatin remodeling, affecting histone acetylation/deacetylation balance. Recently, class I histone deacetylases (HDACs) inhibition has been reported to modulate BDNF mRNA expression and to attenuate morphological and behavioral phenomena related to EtOH exposure. However, the role played by different HDAC isoforms in EtOH induced plasticity is still unclear. METHODS: We investigated the effects induced by acute EtOH exposure on the protein levels of class I HDAC 1-3 isoforms of wild type (WT) and BDNF heterozygous mice (BDNF(+/-)), in nuclear and cytoplasmic extracts of specific brain regions associated with EtOH addiction. RESULTS: Nuclear HDAC 1-3 levels were markedly reduced after acute EtOH treatment in the caudate putamen (CPu) of WT mice only. Furthermore, CPu basal levels of nuclear HDAC isoforms were significantly lower in BDNF(+/-) mice compared to WT. With the exception of nuclear HDAC 3, no significant changes were observed after acute EtOH treatment in the prefrontal cortex (PFCx) of BDNF(+/-) and WT mice. In this area, the nuclear HDAC basal levels were significantly different between the two experimental groups. CONCLUSIONS: These results provide details about EtOH effects on class I HDAC isoforms and strongly support a correlation between BDNF and class I HDACs, suggesting a possible influence of BNDF on these enzymes. PMID- 26361717 TI - Observing the revolution: A commentary on the new GeSIDA HIV guidelines. PMID- 26361716 TI - Serological evidence that activation of ubiquitous human herpesvirus-6 (HHV-6) plays a role in chronic idiopathic/spontaneous urticaria (CIU). AB - Acute infection with viral pathogens in the herpesviridae family can trigger acute urticaria, and reactivation of herpesviridae is associated with cutaneous urticarial-like syndromes such as drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DRESS). Reactivation of latent herpesviridae has not been studied systematically in chronic idiopathic/spontaneous urticaria (CIU). This review proposes that CIU is an inflammatory disorder with autoimmune features (termed 'CVU' for chronic viral urticaria), based on serology consistent with the hypothesis that reactivation of a latent herpesvirus or -viruses may play a role in CIU. Serology obtained from a cohort of omalizumab (Xolair)-dependent patients with severe CIU was consistent with previous HHV-6 infection, persistent viral gene expression and replication. CIU patients also exhibited serological evidence of increased immune response to HHV-4 (Epstein-Barr virus, or EBV) but not all CIU patients were infected with EBV. These observations, combined with case reports of CIU response to anti-viral therapy, suggest that HHV-6, possibly interacting with HHV-4 in cutaneous tissues, is a candidate for further prospective study as a co-factor in CIU. PMID- 26361719 TI - High-throughput screening approaches and combinatorial development of biomaterials using microfluidics. AB - From the first microfluidic devices used for analysis of single metabolic by products to highly complex multicompartmental co-culture organ-on-chip platforms, efforts of many multidisciplinary teams around the world have been invested in overcoming the limitations of conventional research methods in the biomedical field. Close spatial and temporal control over fluids and physical parameters, integration of sensors for direct read-out as well as the possibility to increase throughput of screening through parallelization, multiplexing and automation are some of the advantages of microfluidic over conventional, 2D tissue culture in vitro systems. Moreover, small volumes and relatively small cell numbers used in experimental set-ups involving microfluidics, can potentially decrease research cost. On the other hand, these small volumes and numbers of cells also mean that many of the conventional molecular biology or biochemistry assays cannot be directly applied to experiments that are performed in microfluidic platforms. Development of different types of assays and evidence that such assays are indeed a suitable alternative to conventional ones is a step that needs to be taken in order to have microfluidics-based platforms fully adopted in biomedical research. In this review, rather than providing a comprehensive overview of the literature on microfluidics, we aim to discuss developments in the field of microfluidics that can aid advancement of biomedical research, with emphasis on the field of biomaterials. Three important topics will be discussed, being: screening, in particular high-throughput and combinatorial screening; mimicking of natural microenvironment ranging from 3D hydrogel-based cellular niches to organ-on-chip devices; and production of biomaterials with closely controlled properties. While important technical aspects of various platforms will be discussed, the focus is mainly on their applications, including the state-of-the-art, future perspectives and challenges. STATEMENT OF SIGNIFICANCE: Microfluidics, being a technology characterized by the engineered manipulation of fluids at the submillimeter scale, offers some interesting tools that can advance biomedical research and development. Screening platforms based on microfluidic technologies that allow high-throughput and combinatorial screening may lead to breakthrough discoveries not only in basic research but also relevant to clinical application. This is further strengthened by the fact that reliability of such screens may improve, since microfluidic systems allow close mimicking of physiological conditions. Finally, microfluidic systems are also very promising as micro factories of a new generation of natural or synthetic biomaterials and constructs, with finely controlled properties. PMID- 26361718 TI - Short-course androgen deprivation therapy and the risk of death from high-risk prostate cancer in men undergoing external beam radiation therapy and brachytherapy. AB - PURPOSE: We estimated the risks of prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM) in men with high-risk prostate cancer (PC) undergoing external beam radiation therapy and brachytherapy with short-course androgen deprivation therapy (ADT) (median 4 months) as compared with men with more favorable-risk PC undergoing standard of care as per the National Comprehensive Cancer Network guidelines. METHODS AND MATERIALS: The prospective study cohort comprised 6595 consecutively treated men with T1-4 N0M0 PC whose treatment included brachytherapy between October 16, 1997, and May 28, 2013. Fine and Gray competing risk regression and Cox regression analyses were used to assess the risks of PCSM and ACM in men with high, unfavorable intermediate, and favorable intermediate risk as compared with low-risk PC. RESULTS: After median followup of 7.76 years, 820 men died (12.43%): 72 of PC (8.78%). Men with favorable intermediate-risk PC did not have significantly increased PCSM risk as compared with men with low-risk PC (adjusted hazard ratio [AHR], 1.26; 95% confidence interval [CI] 0.56, 2.88; p-Value 0.58), whereas men with high-risk PC (AHR, 3.74; 95% CI 1.12, 12.53; p-Value 0.032) and unfavorable intermediate-risk PC (AHR, 3.10; 95% CI 1.43, 6.72; p-Value 0.004) did. Based on 10-year adjusted point estimates of PCSM and ACM for men with high-risk PC being 6.01% (95% CI 3.79%, 8.94%) and 21.30% (95% CI 17.45%, 25.42%), respectively, PCSM comprised 28% of ACM. CONCLUSIONS: In the setting of external beam radiation therapy and brachytherapy, men with high-risk PC have low absolute adjusted estimates of PCSM (~6%) during the first decade after treatment despite receiving only short-course ADT. Whether long-term ADT can lower PCSM and improve survival in these men requires additional study. PMID- 26361720 TI - Data-driven optimized flip angle selection for T1 estimation from spoiled gradient echo acquisitions. AB - PURPOSE: Define criteria for selection of optimal flip angle sets for T1 estimation and evaluate effects on T1 mapping. THEORY AND METHODS: Flip angle sets for spoiled gradient echo-based T1 mapping were selected by minimizing T1 estimate variance weighted by the joint density of M0 and T1 in an initial acquisition. The effect of optimized flip angle selection on T1 estimate error was measured using simulations and experimental data in the human and rat brain. RESULTS: For two-point acquisitions, optimized angle sets were similar to those proposed by other groups and, therefore, performed similarly. For multipoint acquisitions, optimal angle sets for T1 mapping in the brain consisted of a repetition of two angles. Implementation of optimal angles reduced T1 estimate variance by 30-40% compared with a multipoint acquisition using a range of angles. Performance of the optimal angle set was equivalent to that of a repetition of the two-angle set selected using criteria proposed by other researchers. CONCLUSION: Repetition of two carefully selected flip angles notably improves the precision of resulting T1 estimates compared with acquisitions using a range of flip angles. This work provides a flexible and widely applicable optimization method of particular use for those who repeatedly perform T1 estimation. Magn Reson Med 76:792-802, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26361721 TI - Nootropic potential of Ashwagandha leaves: Beyond traditional root extracts. AB - Rapidly increasing aging population and environmental stressors are the two main global concerns of the modern society. These have brought in light rapidly increasing incidence of a variety of pathological conditions including brain tumors, neurodegenerative & neuropsychiatric disorders, and new challenges for their treatment. The overlapping symptoms, complex etiology and lack of full understanding of the brain structure and function to-date further complicate these tasks. On the other hand, several herbal reagents with a long history of their use have been asserted to possess neurodifferentiation, neuroregenerative and neuroprotective potentials, and hence been recommended as supplement to enhance and maintain brain health and function. Although they have been claimed to function by holistic approach resulting in maintaining body homeostasis and brain health, there are not enough laboratory studies in support to these and mechanism(s) of such beneficial activities remain largely undefined. One such herb is Ashwagandha, also called "Queen of Ayurveda" for its popular use in Indian traditional home medicine because of its extensive benefits including anticancer, anti-stress and remedial potential for aging and neurodegenerative pathologies. However, active principles and underlying mechanism(s) of action remain largely unknown. Here we provide a review on the effects of Ashwagandha extracts and active principles, and underlying molecular mechanism(s) for brain pathologies. We highlight our findings on the nootropic potential of Ashwagandha leaves. The effects of Ashwagandha leaf extracts are multidimensional ranging from differentiation of neuroblastoma and glioma cells, reversal of Alzheimer and Parkinson's pathologies, protection against environmental neurotoxins and enhancement of memory. PMID- 26361722 TI - Neuroprotection by JM-20 against oxygen-glucose deprivation in rat hippocampal slices: Involvement of the Akt/GSK-3beta pathway. AB - Cerebral ischemia is the third most common cause of death and a major cause of disability worldwide. Beyond a shortage of essential metabolites, ischemia triggers many interconnected pathophysiological events, including excitotoxicity, oxidative stress, inflammation and apoptosis. Here, we investigated the neuroprotective mechanisms of JM-20, a novel synthetic molecule, focusing on the phosphoinositide-3-kinase (PI3K)/Akt survival pathway and glial cell response as potential targets of JM-20. For this purpose, we used organotypic hippocampal slice cultures exposed to oxygen-glucose deprivation (OGD) to achieve ischemic/reperfusion damage in vitro. Treatment with JM-20 at 0.1 and 10 MUM reduced PI incorporation (indicative of cell death) after OGD. OGD decreased the phosphorylation of Akt (pro-survival) and GSK 3beta (pro-apoptotic), resulting in respective inhibition and activation of these proteins. Treatment with JM20 prevented the reduced phosphorylation of these proteins after OGD, representing a shift from pro-apoptotic to pro-survival signaling. The OGD-induced activation of caspase-3 was also attenuated by JM-20 treatment at 10 MUM. Moreover, in cultures treated with JM-20 and exposed to OGD conditioning, we observed a decrease in activated microglia, as well as a decrease in interleukin (IL)-1beta, IL-6 and tumor necrosis factor (TNF)-alpha release into the culture medium, while the level of the anti-inflammatory IL-10 increased. GFAP immunostaining and IB4 labeling showed that JM-20 treatment significantly augmented GFAP immunoreactivity after OGD, when compared with cultures exposed to OGD only, suggesting the activation of astroglial cells. Our results confirm that JM-20 has a strong neuroprotective effect against ischemic injury and suggest that the mechanisms involved in this effect may include the modulation of reactive astrogliosis, as well as neuroinflammation and the anti-apoptotic cell signaling pathway. PMID- 26361723 TI - Nanothin Coculture Membranes with Tunable Pore Architecture and Thermoresponsive Functionality for Transfer-Printable Stem Cell-Derived Cardiac Sheets. AB - Coculturing stem cells with the desired cell type is an effective method to promote the differentiation of stem cells. The features of the membrane used for coculturing are crucial to achieving the best outcome. Not only should the membrane act as a physical barrier that prevents the mixing of the cocultured cell populations, but it should also allow effective interactions between the cells. Unfortunately, conventional membranes used for coculture do not sufficiently meet these requirements. In addition, cell harvesting using proteolytic enzymes following coculture impairs cell viability and the extracellular matrix (ECM) produced by the cultured cells. To overcome these limitations, we developed nanothin and highly porous (NTHP) membranes, which are ~20-fold thinner and ~25-fold more porous than the conventional coculture membranes. The tunable pore size of NTHP membranes at the nanoscale level was found crucial for the formation of direct gap junctions-mediated contacts between the cocultured cells. Differentiation of the cocultured stem cells was dramatically enhanced with the pore size-customized NTHP membrane system compared to conventional coculture methods. This was likely due to effective physical contacts between the cocultured cells and the fast diffusion of bioactive molecules across the membrane. Also, the thermoresponsive functionality of the NTHP membranes enabled the efficient generation of homogeneous, ECM-preserved, highly viable, and transfer-printable sheets of cardiomyogenically differentiated cells. The coculture platform developed in this study would be effective for producing various types of therapeutic multilayered cell sheets that can be differentiated from stem cells. PMID- 26361724 TI - Clinical Relevance Commentary in Response to: First dorsal interosseous muscle contraction results in radiographic reduction of healthy thumb carpometacarpal joint. PMID- 26361725 TI - Brain accumulation of the EML4-ALK inhibitor ceritinib is restricted by P glycoprotein (P-GP/ABCB1) and breast cancer resistance protein (BCRP/ABCG2). AB - We aimed to clarify the roles of the multidrug transporters ABCB1 and ABCG2 in oral availability and brain accumulation of ceritinib, an oral anaplastic lymphoma kinase (ALK) inhibitor used to treat metastatic non-small cell lung cancer (NSCLC) after progression on crizotinib. Importantly, NSCLC is prone to form brain metastases. Transport of ceritinib by human (h) ABCB1 or hABCG2 or mouse (m) Abcg2 was assessed in vitro. To study the single and combined roles of Abcb1a/1b and Abcg2 in ceritinib disposition in vivo, we used appropriate knockout mouse strains. Ceritinib was very efficiently transported by hABCB1, and efficiently by hABCG2 and mAbcg2 in vitro, and transport was specifically inhibited by the ABCB1 inhibitor zosuquidar and ABCG2 inhibitor Ko143, respectively. Absorption and 24-h oral availability were not significantly affected by the absence of Abcb1 and/or Abcg2, but the brain concentrations were greatly increased (>38-fold) in Abcb1a/1b(-/-) mice at 3 and 24h after oral administration of 20mg/kg ceritinib. The brain concentrations increased another ~ 3-fold (to >90-fold) in Abcb1a/1b;Abcg2(-/-) mice, indicating that there was a significant additional effect of Abcg2-mediated transport of ceritinib as well in vivo. Overall, brain accumulation, but not the 24-h oral availability of ceritinib were profoundly restricted by Abcb1a/1b and Abcg2, with Abcb1a/1b being the dominant efflux protein. Our data suggest that coadministration of ceritinib with a dual ABCB1 and ABCG2 inhibitor may improve treatment of brain (micro) metastases positioned behind a functionally intact blood-brain barrier, and possibly also of tumors resistant to ceritinib due to ABCB1 or ABCG2 overexpression. PMID- 26361726 TI - Diosmin downregulates the expression of T cell receptors, pro-inflammatory cytokines and NF-kappaB activation against LPS-induced acute lung injury in mice. AB - Diosmin, a natural flavonoid glycoside present abundantly in the pericarp of various citrus fruits. Because of its anti-inflammatory and antioxidant properties, it can be used in many diseases. In this study, we investigated the possible protective mechanisms of the diosmin on LPS-induced lung injury through inhibition of T cell receptors, pro-inflammatory cytokines and NF-kappaB activation. Animals were pretreated with diosmin (50 and 100mg/kg, p.o.) for seven days prior to lipopolysaccharides (LPS) treatment. LPS administration increased neutrophils, monocytes, lymphocytes, total leukocyte count (TLC) and platelets which were decreased by diosmin. We observed that mice exposed to LPS showed increased malondialdehyde level and MPO activity whereas marked decrease in glutathione content. These changes were significantly reversed by treatment with diosmin in a dose dependent manner. Diosmin treatment showed a substantial reduction in T cell (CD4(+) and CD8(+)) receptors and pro-inflammatory (IL-2(+) and IL-17(+)) cytokines in whole blood. In addition, RT-PCR analysis revealed increased mRNA expression of IL-6, IL-17, TNF-alpha, and NF-kappaB in the LPS group, while reduced by treatment with diosmin. Western blot analysis confirmed the increased protein expression of IL-1beta, TNF-alpha and NF-kappaB p65 in the LPS group and treatment of animals with diosmin reversed these effects. The levels of cytoplasmic p-IkappaB-alpha and p-NF-kappaB p65 expression also were mitigated by diosmin. The histological examinations revealed protective effect of diosmin while LPS group aggravated lung injury. These results support the potential for diosmin to be investigated as a potential agent for the treatment of lung injury and inflammatory diseases. PMID- 26361727 TI - Computational and functional analysis of biopharmaceutical drugs in zebrafish: Erythropoietin as a test model. AB - The zebrafish (Danio rerio) is a very popular vertebrate model system, especially embryos represent a valuable tool for in vivo pharmacological assays. This is mainly due to the zebrafish advantages when compared to other animal models. Erythropoietin is a glycoprotein hormone that acts principally on erythroid progenitors, stimulating their survival, proliferation and differentiation. Recombinant human erythropoietin (rhEPO) has been widely used in medicine to treat anemia and it is one of the best-selling biotherapeutics worldwide. The recombinant molecule, industrially produced in CHO cells, has the same amino acid sequence of endogenous human erythropoietin, but differs in the glycosylation pattern. This may influence efficacy and safety, particularly immunogenicity, of the final product. We employed the zebrafish embryo as a vertebrate animal model to perform in vivo pharmacological assays. We conducted a functional analysis of rhEPO alpha Eprex((r)) and two biosimilars, the erythropoietin alpha Binocrit((r)) and zeta Retacrit((r)). By in silico analysis and 3D modeling we proved the interaction between recombinant human erythropoietin and zebrafish endogenous erythropoietin receptor. Then we treated zebrafish embryos with the 3 rhEPOs and we investigated their effect on erythrocytes production with different assays. By real time-PCR we observed the relative upregulation of gata1 (2.4 +/- 0.3 fold), embryonic alpha-Hb (1.9 +/- 0.2 fold) and beta-Hb (1.6 +/- 0.1 fold) transcripts. A significant increase in Stat5 phosphorylation was also assessed in embryos treated with rhEPOs when compared with the negative controls. Live imaging in tg (kdrl:EGFP; gata1:ds-red) embryos, o-dianisidine positive area quantification and cyanomethemoglobin content quantification revealed a 1.8 +/- 0.3 fold increase of erythrocytes amount in embryos treated with rhEPOs when compared with the negative controls. Finally, we verified that recombinant human erythropoietins did not cause any inflammatory response in the treated embryos. Our data showed that zebrafish embryo can be a valuable tool to study in vivo effects of complex pharmacological compounds, such as recombinant human glycoproteins, allowing to perform fast and reproducible pharmacological assays with excellent results. PMID- 26361729 TI - Boswellic acids target the human immune system-modulating antimicrobial peptide LL-37. AB - The antimicrobial peptide LL-37 is the sole member of the human cathelicidin family with immune system-modulating properties and roles in autoimmune disease development. Small molecules able to interact with LL-37 and to modulate its functions have not been described yet. Boswellic acids (BAs) are pentacyclic triterpene acids that are bioactive principles of frankincense extracts used as anti-inflammatory remedies. Although various anti-inflammatory modes of action have been proposed for BAs, the pharmacological profile of these compounds is still incompletely understood. Here, we describe the identification of human LL 37 as functional target of BAs. In unbiased target fishing experiments using immobilized BAs as bait and human neutrophils as target source, LL-37 was identified as binding partner assisted by MALDI-TOF mass spectrometry. Thermal stability experiments using circular dichroism spectroscopy confirm direct interaction between BAs and LL-37. Of interest, this binding of BAs resulted in an inhibition of the functionality of LL-37. Thus, the LPS-neutralizing properties of isolated LL-37 were inhibited by 3-O-acetyl-beta-BA (Abeta-BA) and 3-O-acetyl-11-keto-beta-BA (AKbeta-BA) in a cell-free limulus amoebocyte lysate assay with EC50=0.2 and 0.8 MUM, respectively. Also, LL-37 activity was inhibited by these BAs in LL-37-enriched supernatants of stimulated neutrophils or human plasma derived from stimulated human whole blood. Together, we reveal BAs as inhibitors of LL-37, which might be a relevant mechanism underlying the anti inflammatory properties of BAs and suggests BAs as suitable chemical tools or potential agents for intervention with LL-37 and related disorders. PMID- 26361730 TI - Jubanines F-J, cyclopeptide alkaloids from the roots of Ziziphus jujuba. AB - Five Ib-type cyclopeptide alkaloids, jubanines F-J (1-5), and three known compounds, nummularine B (6), daechuine-S3 (7), and mucronine K (8) were isolated from the roots of Ziziphus jujuba. Their structures were fully characterized by spectroscopic analyses in combination with chemical derivatization. Compounds 1 3, and 6 were evaluated for their antiviral activity against the porcine epidemic diarrhea virus (PEDV). Compounds 2, 3, and 6 showed potent inhibitory effects on PEDV replication. PMID- 26361728 TI - Repeated administration of phytocannabinoid Delta(9)-THC or synthetic cannabinoids JWH-018 and JWH-073 induces tolerance to hypothermia but not locomotor suppression in mice, and reduces CB1 receptor expression and function in a brain region-specific manner. AB - These studies probed the relationship between intrinsic efficacy and tolerance/cross-tolerance between ?(9)-THC and synthetic cannabinoid drugs of abuse (SCBs) by examining in vivo effects and cellular changes concomitant with their repeated administration in mice. Dose-effect relationships for hypothermic effects were determined in order to confirm that SCBs JWH-018 and JWH-073 are higher efficacy agonists than ?(9)-THC in mice. Separate groups of mice were treated with saline, sub-maximal hypothermic doses of JWH-018 or JWH-073 (3.0mg/kg or 10.0mg/kg, respectively) or a maximally hypothermic dose of 30.0mg/kg ?(9)-THC once per day for 5 consecutive days while core temperature and locomotor activity were monitored via biotelemetry. Repeated administration of all drugs resulted in tolerance to hypothermic effects, but not locomotor effects, and this tolerance was still evident 14 days after the last drug administration. Further studies treated mice with 30.0mg/kg ?(9)-THC once per day for 4 days, then tested with SCBs on day 5. Mice with a ?(9)-THC history were cross-tolerant to both SCBs, and this cross-tolerance also persisted 14 days after testing. Select brain regions from chronically treated mice were examined for changes in CB1 receptor expression and function. Expression and function of hypothalamic CB1Rs were reduced in mice receiving chronic drugs, but cortical CB1R expression and function were not altered. Collectively, these data demonstrate that repeated ?(9)-THC, JWH-018 and JWH-073 can induce long-lasting tolerance to some in vivo effects, which is likely mediated by region-specific downregulation and desensitization of CB1Rs. PMID- 26361731 TI - The cause and influence of sequentially assembling higher and lower deacetylated chitosans on the membrane formation of microcapsule. AB - Alginate-chitosan (AC) microcapsules with desired strength and biocompatibility are preferred in cell-based therapy. Sequential assembly of higher and lower deacetylated chitosans (C1 and C2 ) on alginate has produced AC1 C2 microcapsule with improved membrane strength and biocompatibility. In this article, the assembly and complexation processes of two cationic chitosans on anionic alginate were concerned, and the cause and influence of sequentially assembling chitosans on AC1 C2 microcapsules membrane formation were evaluated. It was found that C1 complexation was the key factor for deciding the membrane thickness of AC1 C2 microcapsule. Specifically, the binding amount of C2 positively related to the binding amount of C1 , which suggested the first layer by C1 complexation on alginate had no obvious resistance on the sequential cationic C2 complexation. Further analyses demonstrated that outward migration of alginate molecules and inward diffusion of both chitosans under electrostatic interaction contributed to the sequential coating of C2 on first C1 layer. Moreover, C2 complexation through the surface to inner layer of membrane helped smoothen the first layer by C1 complexation that displayed a synergy role on the formation of AC1 C2 microcapsule membrane. Therefore, the two chitosans played different roles and synergistically contributed to membrane properties that can be easily regulated with membrane complexation time. PMID- 26361732 TI - Role of the Yersinia YopJ protein in suppressing interleukin-8 secretion by human polymorphonuclear leukocytes. AB - Polymorphonuclear leukocytes, in addition to their direct bactericidal activities, produce cytokines involved in the activation and regulation of the innate and adaptive immune response to infection. In this study we evaluated the cytokine response of human PMNs following incubation with the pathogenic Yersinia species. Yersinia pestis strains with the pCD1 virulence plasmid, which encodes cytotoxic Yop proteins that are translocated into host cells, stimulated little or no cytokine production compared to pCD1-negative strains. In particular, PMNs incubated with pCD1-negative Y. pestis secreted 1000-fold higher levels of interleukin-8 (IL-8 or CXCL8), a proinflammatory chemokine important for PMN recruitment and activation. Deletion of yopE, -H, -T, -M or ypkA had no effect on pCD1-dependent inhibition, whereas deletion of yopJ resulted in significantly increased IL-8 production. Like Y. pestis, the enteropathogenic Yersinia species inhibited IL-8 secretion by PMNs, and strains lacking the virulence plasmid induced high levels of IL-8. Our results show that virulence plasmid-encoded effector Yops, particularly YopJ, prevent IL-8 secretion by human PMNs. Suppression of the chemotactic IL-8 response by Y. pestis may contribute to the delayed PMN recruitment to the infected lymph node that typifies bubonic plague. PMID- 26361733 TI - The bifurcation of the cyanogenic glucoside and glucosinolate biosynthetic pathways. AB - The biosynthetic pathway for the cyanogenic glucoside dhurrin in sorghum has previously been shown to involve the sequential production of (E)- and (Z)-p hydroxyphenylacetaldoxime. In this study we used microsomes prepared from wild type and mutant sorghum or transiently transformed Nicotiana benthamiana to demonstrate that CYP79A1 catalyzes conversion of tyrosine to (E)-p hydroxyphenylacetaldoxime whereas CYP71E1 catalyzes conversion of (E)-p hydroxyphenylacetaldoxime into the corresponding geometrical Z-isomer as required for its dehydration into a nitrile, the next intermediate in cyanogenic glucoside synthesis. Glucosinolate biosynthesis is also initiated by the action of a CYP79 family enzyme, but the next enzyme involved belongs to the CYP83 family. We demonstrate that CYP83B1 from Arabidopsis thaliana cannot convert the (E)-p hydroxyphenylacetaldoxime to the (Z)-isomer, which blocks the route towards cyanogenic glucoside synthesis. Instead CYP83B1 catalyzes the conversion of the (E)-p-hydroxyphenylacetaldoxime into an S-alkyl-thiohydroximate with retention of the configuration of the E-oxime intermediate in the final glucosinolate core structure. Numerous microbial plant pathogens are able to detoxify Z-oximes but not E-oximes. The CYP79-derived E-oximes may play an important role in plant defense. PMID- 26361735 TI - Synthesis of five and six-membered heterocycles bearing an arylpiperazinylalkyl side chain as orally active antinociceptive agents. AB - A number of heterocycles bearing an arylpiperazinylalkyl side chain and structurally related to the previously described lead ET1 (4-amino-6-methyl-2-[3 (4-p-tolylpiperazin-1-yl)propyl]-5-vinylpyridazin-3(2H)-one) was synthesized and tested for their antinociceptive activity in Writhing Test. Many compounds, tested at doses of 20-40 mg/kg po were able to reduce the number of abdominal constrictions by more than 47% and, in same cases, the potency is comparable to lead ET1 as for 5e, 24a, 27b and 27c. The analgesia induced by the active compounds was completely prevented by pretreatment with alpha2-antagonist yohimbine, confirming the involvement of the adrenergic system in the mechanism of action for these new compounds. PMID- 26361734 TI - Linking aptamer-ligand binding and expression platform folding in riboswitches: prospects for mechanistic modeling and design. AB - The power of riboswitches in regulation of bacterial metabolism derives from coupling of two characteristics: recognition and folding. Riboswitches contain aptamers, which function as biosensors. Upon detection of the signaling molecule, the riboswitch transduces the signal into a genetic decision. The genetic decision is coupled to refolding of the expression platform, which is distinct from, although overlapping with, the aptamer. Early biophysical studies of riboswitches focused on recognition of the ligand by the aptamer-an important consideration for drug design. A mechanistic understanding of ligand-induced riboswitch RNA folding can further enhance riboswitch ligand design, and inform efforts to tune and engineer riboswitches with novel properties. X-ray structures of aptamer/ligand complexes point to mechanisms through which the ligand brings together distal strand segments to form a P1 helix. Transcriptional riboswitches must detect the ligand and form this P1 helix within the timescale of transcription. Depending on the cell's metabolic state and cellular environmental conditions, the folding and genetic outcome may therefore be affected by kinetics of ligand binding, RNA folding, and transcriptional pausing, among other factors. Although some studies of isolated riboswitch aptamers found homogeneous, prefolded conformations, experimental, and theoretical studies point to functional and structural heterogeneity for nascent transcripts. Recently it has been shown that some riboswitch segments, containing the aptamer and partial expression platforms, can form binding-competent conformers that incorporate an incomplete aptamer secondary structure. Consideration of the free energy landscape for riboswitch RNA folding suggests models for how these conformers may act as transition states-facilitating rapid, ligand-mediated aptamer folding. PMID- 26361736 TI - New carbocyclic N(6)-substituted adenine and pyrimidine nucleoside analogues with a bicyclo[2.2.1]heptane fragment as sugar moiety; synthesis, antiviral, anticancer activity and X-ray crystallography. AB - New nucleoside analogues with an optically active bicyclo[2.2.1]heptane skeleton as sugar moiety and 6-substituted adenine were synthesized by alkylation of 6 chloropurine intermediate. Thymine and uracil analogs were synthesized by building the pyrimidine ring on amine 1. X-ray crystallography confirmed an exo coupling of the thymine to the ring and an L configuration of the nucleoside analogue. The library of compounds was tested for their inhibitory activity against influenza virus A?California/07/09 (H1N1)pdm09 and coxsackievirus B4 in cell culture. Compounds 13a and 13d are the most promising for their antiviral activity against influenza, and compound 3c against coxsackievirus B4. Compounds 3b and 3g were tested for anticancer activity. PMID- 26361737 TI - Design and synthesis of conformationally constrained hydroxylated 4-phenyl-2-aryl chromenopyridines as novel and selective topoisomerase II-targeted antiproliferative agents. AB - To develop novel selective topoisomerase II inhibitors, we designed and synthesized a series of conformationally constrained hydroxylated 4-phenyl-2-aryl chromenopyridines and evaluated their topoisomerase inhibitory activity and cytotoxicity against three human cancer cell lines (DU145, HCT15, and T47D) and a normal cell line (MCF10A). All of the prepared compounds displayed stronger or similar topoisomerase II inhibitory activity as well as cytotoxicity against three human cancer cell lines compared to etoposide. Compounds 10a, 10g, 11a, 11f, 11g, 12a, 12f, and 12g especially showed stronger topoisomerase II inhibitory activity as compared to etoposide at both 100 MUM and 20 MUM. A structure-activity relationship study revealed that hydroxyphenyl moiety at 4 position of pyridine and ortho-hydroxyphenyl or thienyl moiety at 2-position of pyridine has an important role in displaying selective topoisomerase II inhibition. The compound 12b with para-hydroxyphenyl and meta-hydroxyphenyl at 4- and 2-position of pyridine, respectively, showed the most significant cytotoxicity against all three cancer cell lines, whereas less cytotoxicity to a normal cell line as compared to adriamycin. PMID- 26361738 TI - Broflanilide: A meta-diamide insecticide with a novel mode of action. AB - Broflanilide is a meta-diamide [3-benzamido-N-(4-(perfluoropropan-2 yl)phenyl)benzamide] that exhibits high larvicidal activity against Spodoptera litura. It has been suggested that broflanilide is metabolized to desmethyl broflanilide and that it acts as a noncompetitive resistant-to-dieldrin (RDL) gamma-aminobutyric acid (GABA) receptor antagonist. The binding site of desmethyl broflanilide was demonstrated to be distinct from that of conventional noncompetitive antagonists such as fipronil. It has been proposed that the site of action for desmethyl-broflanilide is close to G336 in the M3 region of the Drosophila RDL GABA receptor. However, although the site of action for desmethyl broflanilide appears to overlap with that of macrocyclic lactones, different modes of actions have been demonstrated for desmethyl-broflanilide and the macrocyclic lactones. The mechanisms underlying the high selectivity of meta diamides are also discussed in this review. Broflanilide is expected to become a prominent insecticide because it is effective against pests with resistance to cyclodienes and fipronil. PMID- 26361739 TI - Deletion of SHATI/NAT8L decreases the N-acetylaspartate content in the brain and induces behavioral deficits, which can be ameliorated by administering N acetylaspartate. AB - We previously identified a novel molecule "SHATI/NAT8L" that exerts an inhibitory effect on methamphetamine (METH)-induced behavioral deficits. Recently, it has been reported that SHATI might function as an aspartate N-acetyltransferase, which synthesizes N-acetylaspartate (NAA) in vitro. However, whether SHATI actually synthesizes NAA in vivo in the brain is still unclear. In this study, we found that both Shati-deleted mice showed significantly lower NAA levels in all brain areas than wild-type (Shati(+/+)) mice using HPLC and fluorescence detection, suggesting that SHATI regulates NAA content in the brain. Next, we measured the levels of monoamines and their metabolites in the adult mouse brain and found that the activities of monoaminergic systems were altered in Shati(-/-) mice. In particular, dopaminergic turnover increased in the nucleus accumbens (NAc) in Shati(-/-) mice, suggesting activation of the dopaminergic system. In fact, basal level of extracellular dopamine, and METH-induced dopamine release in the NAc of Shati(-/-) mice was significantly higher than that of Shati(+/+) and Shati(+/-) mice, which is consistent with findings that Shati(-/-) mice showed enhanced hyperlocomotion induced by METH. Moreover, in the forced swimming test, Shati-deleted mice showed a shortened immobility time, which was improved by intracerebroventricular (i.c.v.) administration of NAA prior to the test in Shati(+/-) but not in Shati(-/-) mice. The i.c.v. preinjection of NAA inhibited dopamine release after high K(+) stimulation in the NAc of Shati(+/+) and Shati(+/-) mice, but not Shati(-/-) mice. These results suggested that the behavioral deficits in Shati-deleted mice were caused by dopaminergic abnormality via deprivation of NAA. PMID- 26361740 TI - CaMKIIdelta and cardiomyocyte Ca(2+) signalling new perspectives on splice variant targeting. AB - Control of cardiomyocyte cytosolic Ca(2+) levels is crucial in determining inotropic status and ischemia/reperfusion stress response. Responsive to fluctuations in cellular Ca(2+), Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is a serine/threonine kinase integral to the processes regulating cardiomyocyte Ca(2+) channels/transporters. CaMKII is primarily expressed either in the deltaB or deltaC splice variant forms, which may mediate differential influences on cardiomyocyte function and pathological response mechanisms. Increases in myocyte Ca(2+) levels promote the binding of a Ca(2+)/calmodulin complex to CaMKII, to activate the kinase. Activity is also maintained through a series of post-translational modifications within a critical region of the regulatory domain of the protein. Recent data indicate that the post translational modification status of CaMKIIdeltaB/deltaC variants may have an important influence on reperfusion outcomes. This study provided the first evidence that the specific type of CaMKII post-translational modification has a role in determining target selectivity of downstream Ca(2+) transporters. The study was also able to demonstrate that the phosphorylated form of CaMKII closely co-localizes with CaMKIIdeltaB in the nuclear/myofilament fraction, contrasting with a co-enrichment of oxidized CaMKII in the membrane fraction with CaMKIIdeltaC . It has also been possible to conclude that a hyper-phosphorylation of CaMKII (Thr287) in reperfused hearts represents a hyper-activation of the CaMKIIdeltaB , which exerts anti-arrhythmic actions through an enhanced capacity to selectively increase sarcoplasmic reticulum Ca(2+) uptake and maintain cytosolic Ca(2+) levels. This suggests that suppression of global CaMKIIdelta may not be an efficacious approach to developing optimal pharmacological interventions for the vulnerable heart. PMID- 26361741 TI - The role of executive functions and theory of mind in children's prosocial lie telling. AB - Children's prosocial lying was examined in relation to executive functioning skills and theory of mind development. Prosocial lying was observed using a disappointing gift paradigm. Of the 79 children (ages 6-12 years) who completed the disappointing gift paradigm, 47 (59.5%) told a prosocial lie to a research assistant about liking their prize. In addition, of those children who told prosocial lies, 25 (53.2%) maintained semantic leakage control during follow-up questioning, thereby demonstrating advanced lie-telling skills. When executive functioning was examined, children who told prosocial lies were found to have significantly higher performance on measures of working memory and inhibitory control. In addition, children who lied and maintained semantic leakage control also displayed more advanced theory of mind understanding. Although children's age was not a predictor of lie-telling behavior (i.e., truthful vs. lie-teller), age was a significant predictor of semantic leakage control, with older children being more likely to maintain their lies during follow-up questioning. PMID- 26361742 TI - Two new types of allergens from the cockroach, Periplaneta americana. AB - Periplaneta americana cockroach is an important source of inhalant indoor allergen resource, and there are more than twenty IgE-binding components identified in P. americana, but only nine allergens were characterized. Our knowledge about cockroach allergens remains poor. In this work, two novel allergen proteins Per a 11 (alpha-amylase) and Per a 12 (chitinase) with molecular weight around 55 and 45 kDa, respectively, were purified and characterized from the midgut of cockroaches. Their primary sequences were determined by Edman degradation, mass spectrometry, and cDNA cloning. Sera from 39 and 30 of 47 (83.0% and 63.8%) patients reacted to Per a 11 and Per a 12 on immunoblots, respectively. The allergenicity of Per a 11 and Per a 12 was further confirmed by competitive ELISA, basophil activation test (BAT), and skin prick test (SPT). They appear to be of importance for the allergic reactions induced by cockroach and have a potential for component-based diagnosis of allergy. PMID- 26361743 TI - Luteolin as an anti-inflammatory and neuroprotective agent: A brief review. AB - According to the World Health Organization, two billion people will be aged 60 years or older by 2050. Aging is a major risk factor for a number of neurodegenerative disorders. These age-related disorders currently represent one of the most important and challenging health problems worldwide. Therefore, much attention has been directed towards the design and development of neuroprotective agents derived from natural sources. These phytochemicals have demonstrated high efficacy and low adverse effects in multiple in vitro and in vivo studies. Among these phytochemicals, dietary flavonoids are an important and common chemical class of bioactive products, found in several fruits and vegetables. Luteolin is an important flavone, which is found in several plant products, including broccoli, pepper, thyme, and celery. Numerous studies have shown that luteolin possesses beneficial neuroprotective effects both in vitro and in vivo. Despite this, an overview of the neuroprotective effects of luteolin has not yet been accomplished. Therefore, the aim of this paper is to provide a review of the available literature regarding the neuroprotective effects of luteolin and its molecular mechanisms of action. Herein, we also review the available literature regarding the chemistry of luteolin, its herbal sources, and bioavailability as a pharmacological agent for the treatment and management of age-related neurodegenerative disorders. PMID- 26361744 TI - 3D genome structure. Organization of the nucleus in space and time. PMID- 26361745 TI - Saphenous vein graft aneurysm fistula formation causing right heart failure: an unusual presentation. AB - Saphenous vein graft aneurysm (SVG) formation after coronary artery bypass grafting is a rare complication of the surgery. We present a case of a 68-year old man with an unusual presentation of such an aneurysm. Thirty-four years after his initial bypass surgery, the patient presented with a fistula formation into his right atrium from a vein graft aneurysm. Late aneurysm formation is thought to occur secondary to atherosclerotic degeneration of the SVG with background hypertension and dyslipidaemia accelerating the process. Diagnostic modalities used to investigate SVG aneurysms include computed tomography, transthoracic echocardiogram, magnetic resonance imaging and cardiac catheterisation. Aneurysms with fistula formation historically require aggressive surgical intervention. Resection of the aneurysm with subsequent revascularisation if required is the surgical norm. SVG aneurysm with fistula formation into a cardiac chamber is a rare complication of coronary artery bypass grafting (CABG), which can occur with atypical presenting symptoms. Physicians should keep in mind the possibility of this occurring in post-CABG patients presenting with heart failure and a new murmur. PMID- 26361746 TI - Glutathione S-transferase P1 suppresses iNOS protein stability in RAW264.7 macrophage-like cells after LPS stimulation. AB - Glutathione S-transferase P1 (GSTP1) is a ubiquitous expressed protein which plays an important role in the detoxification and xenobiotics metabolism. Previous studies showed that GSTP1 was upregulated by the LPS stimulation in RAW264.7 macrophage-like cells and GSTP1 overexpression downregulated lipopolysaccharide (LPS) induced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression. Here we show that GSTP1 physically associates with the oxygenase domain of iNOS by the G-site domain and decreases the protein level of iNOS dimer. Both overexpression and RNA interference (RNAi) experiments indicate that GSTP1 downregulates iNOS protein level and increases S nitrosylation and ubiquitination of iNOS. The Y7F mutant type of GSTP1 physically associates with iNOS, but shows no effect on iNOS protein content, iNOS S nitrosylation, and changes in iNOS from dimer to monomer, suggesting the importance of enzyme activity of GSTP1 in regulating iNOS S-nitrosylation and stability. GSTM1, another member of GSTs shows no significant effect on regulation of iNOS. In conclusion, our study reveals the novel role of GSTP1 in regulation of iNOS by affecting S-nitrosylation, dimerization, and stability, which provides a new insight for analyzing the regulation of iNOS and the anti inflammatory effects of GSTP1. PMID- 26361747 TI - An analysis of the relative frequencies of reported adverse events associated with NSAID administration in dogs and cats in the United Kingdom. AB - This study aimed to analyse UK pharmacovigilance data to quantify adverse events (AEs) associated with the non-steroidal anti-inflammatory drug (NSAID) molecules found in veterinary medicines authorised for use in dogs and cats. It was hypothesised that the frequency of AEs would be lower when associated with cyclo oxygenase-2 selective (coxib), compared to non-selective (non-coxib) NSAIDs. The UK Veterinary Medicines Directorate (VMD) supplied frequencies of AEs derived from Periodic Safety Update Reports subdivided by formulation and species for each NSAID molecule. Frequencies of AEs were similar between species. The five most reported AEs were emesis, death, anorexia, lethargy, and diarrhoea. Reported frequency of emesis, renal insufficiency and death was higher with injectable compared to oral NSAIDs (P = 0.043). Reported frequency of emesis, lethargy and death was higher with coxib, compared to non-coxib NSAIDs (P = 0.029). Median (range) interval since authorisation was shorter for coxibs at 5 (2.5-9) years compared to non-coxibs at 15 (12-25) years. A negative correlation between time elapsed since authorisation and the frequency of AEs was identified (rs = -0.11 to -0.94). Higher frequency of reported AEs with injectable NSAIDs may be related to perioperative administration. The AE frequency associated with coxib and non coxib NSAIDs may be confounded by changes in reporting habits over time. This study highlights the value of interrogating passive surveillance data to identify low frequency AEs and the need to facilitate improvement in recording and collecting AEs in small animal practice. PMID- 26361748 TI - Osteocalcin and bone-specific alkaline phosphatase in Asian elephants (Elephas maximus) at different ages. AB - Bone turnover markers could offer a potential alternative means for the early diagnosis of metabolic bone disease in young growing elephants although the baseline of bone turnover markers in elephant is not well established. The aim of this study was to determine any relationship between the age of captive Asian elephants (Elephas maximus) and markers of bone formation. Serum samples from 24 female Asian elephants were collected to evaluate levels of two bone formation markers, namely, osteocalcin (OC) and bone-specific alkaline phosphatase (BAP). Both intact and N-terminal midfragment OC and BAP were negatively correlated with age. The findings demonstrate that younger elephants have a higher rate of bone turnover than older elephants. Use of these and additional bone markers could lead to the establishment of validated protocols for the monitoring of bone disease in elephants. PMID- 26361749 TI - Comparison of subjective lameness evaluation, force platforms and an inertial sensor system to identify mild lameness in an equine osteoarthritis model. AB - When mild lameness exists, agreement between clinicians is often controversial due to its subjective nature. The goal of the study was to compare subjective and objective methods to identify the presence of mild lameness using an established model of osteoarthritis (OA) in which OA was induced by creating a unilateral carpal osteochondral fragment (OCF) in the middle carpal joint of 16 horses. Subjective lameness evaluations (blinded and unblinded), force platforms (FP), and an inertial-sensor system (ISS) were used to detect forelimb lameness at four time points. Limbs identified as lame by each method were compared as well as compared with the OCF limb at each time point. Spearman correlations were calculated between all outcome parameters. Independent of time, blinded subjective evaluation (54%) and the ISS (60%) identified a higher percentage of horses as lame in the OCF limb compared to FP (40%). Blinded subjective evaluation and the ISS agreed which forelimb was lame more often (50%) compared with blinded subjective evaluation and the FP (38%). Induction of mild lameness within the OCF limb was supported by an increase in the frequency of horses considered lame by both subjective evaluations the ISS and a decrease (3.6%) in mean (among all horses) peak vertical force from baseline to post OCF induction. The percentage of horses identified as lame in the OCF limb, independent of time, was highest with the ISS (60%) followed by blinded subjective evaluation (51%) and the FP (42%). It was concluded that the best agreement was between subjective evaluation and the inertial-sensor system. PMID- 26361750 TI - Expired-air carbon monoxide as a predictor of 16-year risk of all-cause, cardiovascular and cancer mortality. AB - BACKGROUND: Measurement of expired-air carbon monoxide (EACO) is commonly used to ascertain non-smoking status, although it can also reflect exposures not related to smoking. Our aim was to assess 16-year mortality according to EACO measured at baseline, in a general population. METHODS: Our analysis was based on the Third French MONICA population survey (1994-1997). Causes of death were obtained 16 years after inclusion, and assessment of determinants of mortality was based on Cox modeling. RESULTS: EACO was measured in 2232 apparently healthy participants aged 35-64. During follow-up, 195 deaths occurred (19% were due to cardio vascular (CV) causes and 49% to cancer). At baseline, the mean EACO was 11.8 (+/ 7.4)ppm, 4.6 (+/-2.5)ppm, 4.3 (+/-2.2)ppm for current, former and never smokers, respectively (P<0.001). After adjustment for main mortality risk factors and smoking, the hazard ratio (HR) for total mortality was 1.03[95% confidence interval: 1.01-1.06] per 1-unit increase in EACO, and it was 1.04[1.01-1.07] for cancer mortality. Adjusted HR for CV mortality was 1.05[1.01-1.10] but did not remain significant after additional adjustment for smoking (0.98[0.91-1.04]). Interactions between EACO and smoking were not significant. CONCLUSIONS: In a general population, baseline EACO is an independent predictor of 16-year all cause and cancer mortality, after adjustment for confounders including smoking. Given that the effect of EACO is similar among smokers and non-smokers, EACO is probably not solely related to smoking but could also be a marker of inhaled ambient carbon monoxide and/or endogenous production. Besides, smoking better predicts CV mortality than EACO. PMID- 26361751 TI - Racial and ethnic differences in human papillomavirus positivity and risk factors among low-income women in Federally Qualified Health Centers in the United States. AB - Reasons for racial/ethnic disparities in HPV infection are unclear. This study assessed racial/ethnic differences in and risk factors for HPV positivity among low-income women. Data were collected from 984 low-income women visiting Federally Qualified Health Centers across Illinois (2009-2011). Pearson chi square and Logistic regression analyses were used to examine associations with HPV positivity. Our results showed Mexican-born Hispanics had the lowest HPV positivity (16%), followed by non-Hispanic whites (29%), US-born Hispanics (35%), and non-Hispanic blacks (39%). Mexican-born Hispanics reported fewer risk behaviors for HPV positivity, including first sexual intercourse before age 16 years (9% versus 27%), multiple sexual partners in lifetime (48% versus 90%), and current cigarette smoking status (10% versus 35%) when compared to non-Hispanic whites (p<0.001). In multivariate-adjusted logistic regression, being non Hispanic black, first sexual intercourse before age 16 years, increasing numbers of recent or lifetime sexual partners and current cigarette smoking status were associated with a higher likelihood of HPV positivity. Our findings highlight racial/ethnic differences in HPV positivity and risk factors in a population of women with similar socioeconomic characteristics. When measuring HPV risk factors within the Hispanic population, foreign-born status and other mediating factors, such as social norms and cultural characteristics, may be relevant to assess the intragroup heterogeneity. PMID- 26361752 TI - Tobacco use transitions in the United States: The National Longitudinal Study of Adolescent Health. AB - OBJECTIVES: The purpose of this study is to evaluate and describe transitions in cigarette and smokeless tobacco (ST) use, including dual use, prospectively from adolescence into young adulthood. METHODS: The current study utilizes four waves of the National Longitudinal Study of Adolescent Health (Add Health) to examine patterns of cigarette and ST use (within 30 days of survey) over time among a cohort in the United States beginning in 7th-12th grade (1995) into young adulthood (2008-2009). Transition probabilities were estimated using Markov modeling. RESULTS: Among the cohort (N=20,774), 48.7% reported using cigarettes, 12.8% reported using ST, and 7.2% reported dual use (cigarettes and ST in the same wave) in at least one wave. In general, the risk for transitioning between cigarettes and ST was higher for males and those who were older. Dual users exhibited a high probability (81%) of continuing dual use over time. CONCLUSIONS: Findings suggest that adolescents who use multiple tobacco products are likely to continue such use as they move into young adulthood. When addressing tobacco use among adolescents and young adults, multiple forms of tobacco use should be considered. PMID- 26361753 TI - Using behavioral economics to promote healthy behavior toward sun exposure in adolescents and young adults. AB - Skin cancer represents an important public health problem, and it is associated with ultraviolet radiation exposure, particularly at early ages. Unhealthy sun exposure and intentional tanning continue to be the trend among young people. Multiple interventions to raise awareness of the risks of sun exposure have been implemented, without necessarily translating into decreased unhealthy behaviors or skin cancer incidence rates. Behavioral economics adds a set of concepts and tools to potentially boost the efficacy of existing approaches to decrease unhealthy sun exposure. This paper reviews public health interventions that have been based in behavioral economics concepts and their results, and provides examples of new and creative ways physicians and health professionals can actively apply insights from behavioral economics to counsel teenagers and young adults about skin cancer prevention. PMID- 26361754 TI - Lonely hearts don't get checked: On the role of social support in screening for cardiovascular risk. AB - OBJECTIVE: Regular cardiovascular risk screening can prevent cardiovascular disease through timely implementation of lifestyle changes or medication. However, few studies have investigated what factors promote regular screening for risk factors like hypertension and high blood cholesterol. The aim of this study was to investigate the relationship between social support and adherence to cardiovascular risk screening. METHODS: We analyzed data from the Spanish National Health Survey-a cross-sectional representative survey conducted by the Spanish Ministry of Health in 2012 (N=21,007). Participants reported whether they had their blood pressure and cholesterol levels measured by a health professional in the previous 12 months. Social support (i.e., the perception that emotional and practical support was available when needed) was measured with a validated scale. Multiple logistic regressions were conducted adjusted for demographic and health-related factors. RESULTS: Compared to individuals who reported a lack of social support, individuals who perceived sufficient social support were on average twice more likely to report participation in blood pressure screening, OR=2.06, 95% CI [1.60, 2.66] and cholesterol screening, OR=2.85, 95% CI [1.99, 4.09]. These effects were uniform across different demographics and were replicated in a previous wave of the survey. Factors associated with worse screening adherence were low social class, being single or widowed, smoking, alcohol consumption, and no history of cardiovascular risk. DISCUSSION: Perceptions of social support are positively related to cardiovascular risk screening adherence. Future research should investigate what type of social support most effectively increases screening participation among high risk populations. PMID- 26361755 TI - Inhibition of autophagy by 3-MA enhances IL-24-induced apoptosis in human oral squamous cell carcinoma cells. AB - BACKGROUND: Interleukin-24(IL-24), also referred to as melanoma differentiation associated gene-7(mda-7), is a unique member of the IL-10 gene family, which displays nearly ubiquitous cancer-specific toxicity. The most notable feature of IL-24 is selectively induced growth suppression and apoptosis in various cancer cells, with no harmful effects toward normal cells. Autophagy is a self protective mechanism in many kinds of tumor cells that respond to anticancer treatment. It is reported that autophagy inhibition could enhance the effects of many kinds of anticancer treatments, including gene therapy. However, whether IL 24 is effective to treat oral squamous cell carcinomas (OSCC) and if autophagy inhibition could improve the anticancer effect of IL-24 towards OSCC is has not been detected. METHODS: MTT assays were carried out to determine the cell proliferation; Transfection was used to gene transfer; Western Blot was performed to detect the protein level of LC3II, P62, Beclin 1, Cleaved caspase-3, beta Tubulin and beta-actin; Apoptosis rates and cell cycle alteration were analyzed using flow cytometry; Autophagy induction was confirmed by MDC staining, GFP-LC3 staining and transmission electron microscopy. Amount of IL-24 in the culture medium was quantified by ELISA. Apoptosis in vivo was analyzed by TUNEL assay. HE staining was used to observe the morphology of the samples. RESULTS: In the present study, we proved that IL-24 have a novel anticancer effect towards KB cells and that autophagy inhibition could improve the anticancer effect of IL-24. IL-24 treated cells showed autophagy characteristics and autophagy inhibition by 3-methyladenine (3-MA) significantly enhanced IL-24-induced apoptosis. Similar results were obtained in the KB cells xenograft tumor model. CONCLUSIONS: These results suggest that the combination of autophagy inhibitors and IL-24 based on the AdLTR2EF1alpha-mediated gene transfer could be a promising way to cure OSCC. PMID- 26361756 TI - Is radial Extracorporeal Shock Wave Therapy (rEWST) combined with supervised exercises (SE) more effective than sham rESWT and SE in patients with subacromial shoulder pain? Study protocol for a double-blind randomised, sham-controlled trial. AB - BACKGROUND: Subacromial shoulder pain is a common complaint. Radial Extracorporeal Shock Wave Therapy (rESWT) has being increasingly used to treat calcific and non-calcific tendinosis, although there is no evidence of the effectiveness of rESWT in non-calcific tendinosis of the rotator cuff. A randomised single blind study showed that the short-term effect of supervised exercises (SE) was significantly better than rESWT on subacromial shoulder pain, but both groups improved. In a clinical trial on achilles tendinopathy rESWT improved the effectiveness of treatment with eccentric loading. The objective of this present study is to evaluate if rESWT in addition to SE is more effective in improving shoulder pain and function compared with sham rESWT and SE in patients with subacromial shoulder pain. METHODS/DESIGN: This is a double blind, randomised sham-controlled trial which is performed at the shoulder clinic at the Department of Physical Medicine and Rehabilitation in Oslo University Hospital, Norway. One-hundred-forty-four patients with subacromial shoulder pain lasting at least 3 months, age from 25 to 70 years old are included in the trial. Patients are randomly allocated in 1:1 ratio to receive either rESWT or sham rESWT once a week in addition to SE once a week for the initial 4 weeks. Subsequently SE are provided twice a week for 8 weeks. The primary outcome measure is a change in the Shoulder Pain and Disability Index (SPADI) at 24 weeks follow-up. Secondary outcomes include return to work, pain at rest and on activity, function, and health related quality of life. The patients, the physiotherapist providing the exercise regimen and the outcome assessor are blinded to group assignment. The physiotherapist providing the rESWT is not blinded. DISCUSSION: Because of the extensive use of rESWT in the treatment of subacromial shoulder pain the results of this trial will be of importance and have impact on clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov NCT01441830. PMID- 26361757 TI - Classification of substandard factors in perinatal care: development and multidisciplinary inter-rater agreement of the Groningen-system. AB - BACKGROUND: Perinatal audit is an established method for improving the quality of perinatal care. In audit meetings substandard factors (SSF) are identified in cases of perinatal mortality and morbidity. To our knowledge there is no classification system specifically designed for the classification of substandard factors. Such a classification may help to standardise allocation of substandard factors to categories. This will help to prioritise, guide and implement actions in quality improvement programs. METHODS: A classification system of 284 substandard factors (SSF) identified in perinatal audit meetings between 2007 and 2011 was drawn up using the WHO Conceptual Framework for the International Classification for Patient Safety as a starting point. Discussions were held on inter-rater disagreements, inclusion of items, format and organisation and definitions of the main- and subcategories. A guideline was developed. An independent multidisciplinary group tested the classification. Independent of inter-rater agreement the allocations to categories were counted. For the counts in the subcategories one and two, we used the allocations in the main category as reference. The chance corrected agreement between classifiers was tested with Cohen's kappa statistic. RESULTS: The classification consists of 9 main categories with one or two subcategories. The main categories are (1) Equipment and Materials, (2) Medication, (3) Additional tests/ investigations, (4) Transportation , (5) Documentation, (6) Communication, (7) Medical practice, (8) Other and (9) non classifiable. Of 3663 allocations by 13 classifiers 1452 SSF's were allocated (40%) to 'medical practice' and 1247 (34%) to 'documentation'. 118 (3%) times SSF's were not classifiable, mainly due to unclear phrasing of the SSF. The chance corrected agreement of 284 substandard factors in the main category was 0.68 (95% CI 0.66-0.70) and 0.57 (95% CI 0.54-0.59) for the CDG and the IGD respectively. CONCLUSIONS: Classifying substandard factors has given insight into problem area's in perinatal care and can give direction to medical, political and financial quality improvement measures. The Groningen-system has well defined categories and subcategories and the guidelines and examples are clear. The multidisciplinary inter-rater agreement is moderate to good. Improvement of the phrasing of the substandard factors is expected to improve inter-rater agreement. PMID- 26361759 TI - The kitchen as therapy: qualitative assessment of an integrative cuisine workshop for patients undergoing chemotherapy. AB - OBJECTIVE: Patients undergoing chemotherapy frequently suffer from gastrointestinal (GI) symptoms and functional difficulties in preparing and eating meals. We conducted a qualitative assessment of an integrative cuisine workshop program designed for patients receiving chemotherapy, examining the effects of the program on patient-reported GI symptoms and nutritional challenges. PATIENTS AND METHODS: Patients were referred to a complementary/integrative medicine (CIM)-trained physician for consultation, followed by a patient-tailored treatment program. Patients with GI-related symptoms and nutritional concerns were offered a two-session integrative cuisine workshop program. The effects of the workshops were examined using inductive and deductive qualitative research methodologies. Patient narratives, as recorded in the Measure Yourself Concerns and Wellbeing (MYCAW) study tool, and electronic medical files were analyzed. RESULTS: Of 125 patients referred to the integrative cuisine program, 86 participated in at least one workshop. Participants and non participants had similar demographic and disease-related characteristics, as well as quality-of-life (QOL)-related concerns. Inductive analysis suggested that participation in the workshops was helpful in developing social relationships, providing emotional support, and enhancing spirituality and nutritional awareness. Implementing the recommended changes at home led to improved QOL related outcomes. The predominant themes derived from deductive analysis were the implementation of dietary changes and improved gastrointestinal and emotional issues. CONCLUSIONS: Chemotherapy-treated patients participating in an integrative cuisine workshop program showed improved QOL outcomes, specifically GI and emotional-related symptoms, and a reduction in nutritional and functional concerns. Increased knowledge and awareness of nutrition and supplement use ultimately resulted in implementation of the CIM recommendations by patients at home. PMID- 26361758 TI - Subgroups of chemotherapy patients with distinct morning and evening fatigue trajectories. AB - PURPOSE: Purposes of this study were to identify subgroups of patients with distinct trajectories for morning and evening fatigue, evaluate for differences in demographic and clinical characteristics among these subgroups, and compare and contrast the predictors of subgroup membership for morning and evening fatigue. METHODS: Outpatients with breast, gastrointestinal, gynecological, or lung cancer (n = 582) completed questionnaires, a total of six times over two cycles of chemotherapy (CTX). Morning and evening fatigue severity were evaluated using the Lee Fatigue Scale. Latent profile analysis (LPA) was used to identify distinct subgroups. RESULTS: Three latent classes were identified for morning fatigue (i.e., low (31.8 %), high (51.4 %), and very high (16.8 %)) and for evening fatigue (i.e., moderate (20.0 %), high (21.8 %), and very high (58.2 %)). Most of the disease and treatment characteristics did not distinguish among the morning and evening fatigue classes. Compared to the low class, patients in the high and very high morning fatigue classes were younger, had a lower functional status, and higher level of comorbidity. Compared to the moderate class, patients in the very high evening fatigue class were younger, more likely to be female, had child care responsibilities, had a lower functional status, and a higher level of comorbidity. CONCLUSION: LPA allows for the identification of risk factors for more severe fatigue. Since an overlap was not observed across the morning and evening fatigue classes and unique predictors for morning and evening fatigue were identified, these findings suggest that morning and evening fatigue may have distinct underlying mechanisms. PMID- 26361760 TI - Dental abnormalities after chemotherapy in long-term survivors of childhood acute lymphoblastic leukemia 7-40 years after diagnosis. AB - PURPOSE: Factors associated with the long-term dental effects after chemotherapy for childhood malignancies have not been well described. The primary aims of this study were as follows: (1) to assess whether age at diagnosis and treatment related factors are associated with dental defects in survivors of childhood acute lymphoblastic leukemia (ALL) and (2) to assess the survivors' annual expenses for dental treatment compared to reference data. METHODS: This cross sectional study enrolled 111 Norwegian survivors of ALL diagnosed before the age of 16. All of the subjects completed a questionnaire and underwent medical and oral examinations. Dental defects were registered according to the individual defect index, with 0 = no defects and 140 = anodontia, and the caries experience was registered according to the decayed-missing-filled teeth index (DMFT). Age matched reference data were drawn from a national general population survey (n = 555). RESULTS: The mean age at examination was 29.1 years (SD 7.2), and mean follow-up period was 22.9 years (SD 7.3). In a regression model, diagnoses occurring at <=5 years of age (B = -9.6, p < 0.001) and a cumulative dose of anthracyclines >120 mg/m(2) (B = 11.5, p < 0.001) were strongly associated with more severe dental defects. Survivors treated after the age of 5 had experienced more caries than those treated at a younger age [DMFT 9.6 (SD 6.1) vs. 6.0 (SD 4.6), respectively; p = 0.001]. High annual expenses for dental treatment were reported by a larger percentage of the reference population compared to the survivor group (18 vs. 9 %, respectively; p = 0.02). CONCLUSIONS: The age at diagnosis and the dose of anthracyclines appear to be strongly associated with the severity of dental defects, although few survivors reported high annual expenses for dental treatment. The increased risk of dental defects during adulthood should be communicated to ALL survivors. PMID- 26361761 TI - Rapid identification of bacteria from positive blood culture bottles by MALDI-TOF MS following short-term incubation on solid media. AB - Rapid identification of bacteria from blood cultures enables early initiation of appropriate antibiotic treatment in patients with bloodstream infections (BSI). The objective of the present study was to evaluate the use of matrix-associated laser desorption ionization-time of flight (MALDI-TOF) MS after a short incubation on solid media for rapid identification of bacteria from positive blood culture bottles. MALDI-TOF MS was performed after 2.5 and 5.5 h plate incubation of samples from positive blood cultures. Identification scores with values >= 1.7 were accepted as successful identification if the results were confirmed by conventional methods. Conventional methods included MALDI-TOF MS, Vitek 2, and diverse biochemical and agglutination tests after overnight culture. In total, 515 positive blood cultures with monomicrobial bacterial growth representing one blood culture per patient were included in the study. There were 229/515 (44.5%) and 286/515 (55.5%) blood culture bottles with Gram-negative bacteria (GNB) and Gram-positive bacteria (GPB), respectively. MALDI-TOF MS following short-term culture could accurately identify 300/515 (58.3%) isolates at 2.5 h, GNB being identified in greater proportion (180/229; 78.6%) than GPB (120/286; 42.0%). In an additional 124/515 bottles (24.1%), identification was successful at 5.5 h, leading to accurate identification of bacteria from 424/515 (82.3%) blood cultures after short-term culture. Interestingly, 11/24 of the isolated anaerobic bacteria could be identified after 5.5 h. The present study demonstrates, in a large number of clinical samples, that MALDI-TOF MS following short-term culture on solid medium is a reliable and rapid method for identification of bacteria from blood culture bottles with monomicrobial bacterial growth. PMID- 26361763 TI - I feel you-monitoring environmental variables related to asthma in an integrated real-time frame. AB - The study of asthma and other complex diseases has proven to be a "moving target" for researchers due to its complex aetiology, difficulty in definition, and immeasurable environmental effects. A large number of studies regarding the contribution of both genetic and environmental factors often result in contradictory results, in part due to the highly heterogeneous nature of asthma. Recent literature has focused on the epigenetic signatures of asthma caused by environmental factors, highlighting the importance of environment. However, unlike the genetic techniques, environmental assessment still lacks accuracy. A plausible solution for this problem would be an individual-based environmental exposure assessment, relying on new technologies such as personal real-time environmental sensors. This could prove to enable the assessment of the whole environmental exposure-or exposome-matching in terms of precision the genome that is emphasized in most studies so far. In addition, the measurement of the whole array of biological molecules, in response to the environment action, could help understand the context of the disease. The current perspective comprises a beyond genetics integrated vision of omics technology coupled with real-time environmental measures targeting to enhance our comprehension of the disease genesis. PMID- 26361762 TI - Hsp70-1: upregulation via selective phosphorylation of heat shock factor 1 during coxsackieviral infection and promotion of viral replication via the AU-rich element. AB - Coxsackievirus B3 (CVB3) is the primary pathogen of viral myocarditis. Upon infection, CVB3 exploits the host cellular machineries, such as chaperone proteins, to benefit its own infection cycles. Inducible heat shock 70-kDa proteins (Hsp70s) are chaperone proteins induced by various cellular stress conditions. The internal ribosomal entry site (IRES) within Hsp70 mRNA allows Hsp70 to be translated cap-independently during CVB3 infection when global cap dependent translation is compromised. The Hsp70 protein family contains two major members, Hsp70-1 and Hsp70-2. This study showed that Hsp70-1, but not Hsp70-2, was upregulated during CVB3 infection both in vitro and in vivo. Then a novel mechanism of Hsp70-1 induction was revealed in which CaMKIIgamma is activated by CVB3 replication and leads to phosphorylation of heat shock factor 1 (HSF1) specifically at Serine 230, which enhances Hsp70-1 transcription. Meanwhile, phosphorylation of Ser230 induces translocation of HSF1 from the cytoplasm to nucleus, thus blocking the ERK1/2-mediated phosphorylation of HSF1 at Ser307, a negative regulatory process of Hsp70 transcription, further contributing to Hsp70 1 upregulation. Finally, we demonstrated that Hsp70-1 upregulation, in turn, stabilizes CVB3 genome via the AU-rich element (ARE) harbored in the 3' untranslated region of CVB3 genomic RNA. PMID- 26361764 TI - Green tea extract activates AMPK and ameliorates white adipose tissue metabolic dysfunction induced by obesity. AB - PURPOSE: Beneficial effects of green tea (GT) polyphenols against obesity have been reported. However, until this moment the molecular mechanisms of how green tea can modulate obesity and regulates fat metabolism, particularly in adipose tissue, remain poorly understood. The aim of this study was to evaluate the role of GT extract in the adipose tissue of obese animals and its effect on weight gain, metabolism and function (de novo lipogenesis and lipolysis), and the involvement of AMP-activated protein kinase (AMPK). METHODS AND RESULTS: Male Wistar rats were treated with GT by gavage (12 weeks/5 days/week; 500 mg/kg of body weight), and obesity was induced by cafeteria diet (8 weeks). Here, we show that obese rats treated with GT showed a significant reduction in indicators of obesity such as hyperlipidemia, fat synthesis, body weight, and fat depots as compared to those treated with standard control diet. AMPK was induced in adipose tissue in rats that were treated with GT and likely restored insulin sensitivity, increased mRNA expression of GLUT4, reducing the concentrations of plasma and liver lipid content, also stimulating fatty acid oxidation in the same tissue. Importantly, repression of de novo lipogenesis in the adipose tissue, reduced lipid droplets in the liver, and the development of insulin resistance in diet induced obese rats were accompanied by AMPK activation. CONCLUSION: Our study identified that metabolic changes caused by GT intake induced AMPK activation and modulate the expression of genes involved in metabolism, particularly in adipose tissue, thus offering a therapeutic strategy to combat insulin resistance, dyslipidemia, and obesity in rats. PMID- 26361765 TI - Gomisin A is a Novel Isoform-Specific Probe for the Selective Sensing of Human Cytochrome P450 3A4 in Liver Microsomes and Living Cells. AB - Nearly half of prescription medicines are metabolized by human cytochrome P450 (CYP) 3A. CYP3A4 and 3A5 are two major isoforms of human CYP3A and share most of the substrate spectrum. A very limited previous study distinguished the activity of CYP3A4 and CYP3A5, identifying the challenge in predicting CYP3A-mediated drug clearance and drug-drug interaction. In the present study, we introduced gomisin A (GA) with a dibenzocyclooctadiene skeleton as a novel selective probe of CYP3A4. The major metabolite of GA was fully characterized as 8-hydroxylated GA by LC-MS and NMR. CYP3A4 was assigned as the predominant isozyme involved in GA 8 hydroxylation by reaction phenotyping assays, chemical inhibition assays, and correlation studies. GA 8-hydroxylation in both recombinant human CYP3A4 and human liver microsomes followed classic Michaelis-Menten kinetics. The intrinsic clearance values indicated that CYP3A4 contributed 12.8-fold more than CYP3A5 to GA 8-hydroxylation. Molecular docking studies indicated different hydrogen bonds and pi-pi interactions between CYP3A4 and CYP3A5, which might result in the different catalytic activity for GA 8-hydroxylation. Furthermore, GA exhibited a stronger inhibitory activity towards CYP3A4 than CYP3A5, which further suggested a preferred selectivity of CYP3A4 for the transformation of GA. More importantly, GA has been successfully applied to selectively monitor the modulation of CYP3A4 activities by the inducer rifampin in hepG2 cells, which is consistent with the level change of CYP3A4 mRNA expression. In summary, our results suggested that GA could be used as a novel probe for the selective sensing of CYP3A4 in tissue and cell preparations. PMID- 26361766 TI - Modeling cell apoptosis for simulating three-dimensional multicellular morphogenesis based on a reversible network reconnection framework. AB - Morphogenesis in multicellular organisms is accompanied by apoptotic cell behaviors: cell shrinkage and cell disappearance. The mechanical effects of these behaviors are spatiotemporally regulated within multicellular dynamics to achieve proper tissue sizes and shapes in three-dimensional (3D) space. To analyze 3D multicellular dynamics, 3D vertex models have been suggested, in which a reversible network reconnection (RNR) model has successfully expressed 3D cell rearrangements during large deformations. To analyze the effects of apoptotic cell behaviors on 3D multicellular morphogenesis, we modeled cell apoptosis based on the RNR model framework. Cell shrinkage was modeled by the potential energy as a function of individual cell times during the apoptotic phase. Cell disappearance was modeled by merging neighboring polyhedrons at their boundary surface according to the topological rules of the RNR model. To establish that the apoptotic cell behaviors could be expressed as modeled, we simulated morphogenesis driven by cell apoptosis in two types of tissue topology: 3D monolayer cell sheet and 3D compacted cell aggregate. In both types of tissue topology, the numerical simulations successfully illustrated that cell aggregates gradually shrank because of successive cell apoptosis. During tissue shrinkage, the number of cells in aggregates decreased while maintaining individual cell size and shape. Moreover, in case of localizing apoptotic cells within a part of the 3D monolayer cell aggregate, the cell apoptosis caused the global tissue bending by pulling on surrounding cells. In case of localizing apoptotic cells on the surface of the 3D compacted cell aggregate, the cell apoptosis caused successive, directional cell rearrangements from the inside to the surface. Thus, the proposed model successfully provided a basis for expressing apoptotic cell behaviors during 3D multicellular morphogenesis based on an RNR model framework. PMID- 26361769 TI - Simultaneous interactions of pyrimidine ring with BeF2 and BF3 in BeF2???X Pyr???BF3 complexes: non-cooperativity. AB - We investigated the mutual interplay between beryllium and boron bonds in the BeF2???X-Pyr???BF3 complexes (X = CN, F, Cl, Br, H, CH3, OH and NH2, where Pyr and ??? denote pyrimidine ring and beryllium and boron bonds, respectively) at the M06-2X/aug-cc-pVDZ level of theory. The results indicate that non-cooperative effects are observed when the two kinds of noncovalent interactions beryllium and boron bonds coexist in the complexes. These effects were studied in terms of the energetic and geometric features of the complexes. Atoms in molecules (AIM) and natural bond orbital (NBO) analyses were also performed to unveil the mechanism of these interactions in the title complexes. The electron-withdrawing/donating substituents decrease/increase the magnitude of the binding energies compared to the unsubstituted BeF2???X-Pyr???BF3 (X = H) complex. The Esynvalues are in agreement with the geometric features of the complexes. The results stress the importance of the mutual effects between noncovalent interactions involving aromatic systems. PMID- 26361767 TI - 4D subject-specific inverse modeling of the chick embryonic heart outflow tract hemodynamics. AB - Blood flow plays a critical role in regulating embryonic cardiac growth and development, with altered flow leading to congenital heart disease. Progress in the field, however, is hindered by a lack of quantification of hemodynamic conditions in the developing heart. In this study, we present a methodology to quantify blood flow dynamics in the embryonic heart using subject-specific computational fluid dynamics (CFD) models. While the methodology is general, we focused on a model of the chick embryonic heart outflow tract (OFT), which distally connects the heart to the arterial system, and is the region of origin of many congenital cardiac defects. Using structural and Doppler velocity data collected from optical coherence tomography, we generated 4D ([Formula: see text]) embryo-specific CFD models of the heart OFT. To replicate the blood flow dynamics over time during the cardiac cycle, we developed an iterative inverse method optimization algorithm, which determines the CFD model boundary conditions such that differences between computed velocities and measured velocities at one point within the OFT lumen are minimized. Results from our developed CFD model agree with previously measured hemodynamics in the OFT. Further, computed velocities and measured velocities differ by [Formula: see text]15 % at locations that were not used in the optimization, validating the model. The presented methodology can be used in quantifications of embryonic cardiac hemodynamics under normal and altered blood flow conditions, enabling an in-depth quantitative study of how blood flow influences cardiac development. PMID- 26361768 TI - A user-friendly web portal for analyzing conformational changes in structures of Mycobacterium tuberculosis. AB - Initiation of the Tuberculosis Structural Consortium has resulted in the expansion of the Mycobacterium tuberculosis (MTB) protein structural database. Currently, 969 experimentally solved structures are available for 354 MTB proteins. This includes multiple crystal structures for a given protein under different functional conditions, such as the presence of different ligands or mutations. In depth analysis of the multiple structures reveal that subtle differences exist in conformations of a given protein under varied conditions. Therefore, it is immensely important to understand the conformational differences between the multiple structures of a given protein in order to select the most suitable structure for molecular docking and structure-based drug designing. Here, we introduce a web portal ( http://bmi.icmr.org.in/mtbsd/torsion.php ) that we developed to provide comparative data on the ensemble of available structures of MTB proteins, such as Calpha root means square deviation (RMSD), sequence identity, presence of mutations and torsion angles. Additionally, torsion angles were used to perform principal component analysis (PCA) to identify the conformational differences between the structures. Additionally, we present a few case studies to demonstrate this database. Graphical Abstract Conformational changes seen in the structures of the enoyl-ACP reductase protein encoded by the Mycobacterial gene inhA. PMID- 26361770 TI - Second hyperpolarizability of delta shaped disubstituted acetylene complexes of beryllium, magnesium, and calcium. AB - Present theoretical study involves the delta shape complexes of beryllium, magnesium, and calcium where the metal atom interacts perpendicularly with disubstituted acetylene. Most of the complexes are found to be fairly stable. The dependence of second-hyperpolarizability on the basis set with increasing polarization and diffuse functions has been examined which showed the importance of 'f-type' type polarization function for heavy metal (Mg, Ca) and 'd-type' polarization function for beryllium. Larger second hyperpolarizability has been predicted for complexes having significant ground state polarization and low lying excited states favoring strong electronic coupling. Transition energy plays the most significant role in modulating the second hyperpolarizability. PMID- 26361771 TI - Acute Appendicitis in the Adult Population: Modelled Decision Analysis Supports a Conservative Approach. AB - INTRODUCTION: Acute appendicitis represents the commonest cause of acute intra abdominal pathology. Appendectomy and antibiotics are the mainstay of therapy for appendicitis. Evidence is emerging that antibiotics alone may adequately treat most cases of appendicitis. Decision analysis is a quantitative method of examining alternate treatment strategies. This study describes a modelled decision analysis comparing operative and conservative management of appendicitis. METHODS: The base case patient is a healthy, 23-year-old male presenting with migratory pain to the right iliac fossa (RIF) and elevated inflammatory markers. A decision tree was constructed comparing operative and conservative treatment. Rates of complications, failure of conservative therapy, recurrence and utilities were calculated via a systematic literature review. Variables were tested for sensitivity. RESULTS: Overall, conservative management gives a significantly better outcome (51.51 vs 49.87 QALYs). Three variables proved sensitive. Once operative complication rates are lower than 11.5 %, surgical treatment becomes the optimal strategy. If rates of failure of conservative management exceed 12.9 %, surgery becomes optimal. If the utility assigned to a post-operative complication exceeds 0.44, surgery becomes optimal. CONCLUSIONS: This decision analysis supports a conservative strategy, albeit with caveats. If operative complications are low or rates of failure of conservative management remain high, surgery is the preferable strategy. PMID- 26361772 TI - Laparoscopic Major Hepatectomy-Technique and Outcomes. AB - BACKGROUND: With technological innovations especially newer parenchymal transection devices, improved understanding of hepatic anatomy facilitated by better imaging, and reconstructions along with experiences gained from advanced minimal invasive procedures, laparoscopic liver surgery is gaining momentum with more than 5300 reported cases worldwide. Most of the published literature comprises nonanatomical and segmental resections with only few case series having major hepatic resections performed by minimally invasive approach. Aim of this article is to share our technique and experience of total laparoscopic major hepatectomy. METHODS: It is a retrospective analysis of prospectively maintained database of 56 patients, who underwent laparoscopic major hepatectomy for various indications during 2001 to 2013. RESULTS: Of 56 patients operated, 37 had malignant disease and 19 had benign lesions with mean size of 6.0 +/- 2.8 cm. Thirty-four patients underwent right hepatectomy and 22 left with mean age of 54.8 +/- 15.3 years. Mean operating time was 227.4 +/- 51.8 min with mean blood loss 265.5 +/- 143.4 ml and transfusion needed in 10.7 %. Pringle's maneuver was used in 19.6 % with mean occlusion time of 34.0 +/- 11.4 min. Liver-specific complications were observed in 12.5 % and overall complications in 19.6 %. Mean resection margin length in malignant lesions was 2.1 +/- 0.9 cm, with <1 cm margin noted in 5.4 %. Median hospital stay was 8 days (6-29) with readmission rate of 8.9 %, re-intervention rate of 5.3 % and 90 days mortality of 1.7 %. CONCLUSION: Laparoscopic major liver resection is a formidable task. It requires considerable expertise in both, advanced laparoscopy, and liver surgery. It can be feasible, safe, and oncologically adequate in well-selected cases in experience hands. PMID- 26361774 TI - Neutrophils: important contributors to tumor progression and metastasis. AB - The presence of neutrophils in tumors has traditionally been considered to be indicative of a failed immune response against cancers. However, there is now evidence showing that neutrophils can promote tumor growth, and increasingly, the data support an active role for neutrophils in tumor progression to distant metastasis. Neutrophils have been implicated in promoting metastasis in cancer patients, where neutrophil numbers and neutrophil-related factors and functions have been associated with progressive disease. Nevertheless, the role of neutrophils in tumors, both at the primary and secondary sites, remains controversial, with some studies reporting their anti-tumor functions. This review will focus on the data demonstrating a role for neutrophils in both tumor growth and metastasis and will attempt to clarify the discrepancies in the literature. PMID- 26361773 TI - Repeat Hepatectomy for Recurrent Colorectal Liver Metastases: Is it Worth the Challenge? AB - INTRODUCTION: Repeat hepatectomy (RH) is considered a valuable option for management of recurrent colorectal liver metastases (R-CLM). Here, the outcome of RH for R-CLM was compared to that of patients who underwent single hepatectomy (SH) after subdividing the later according to re-recurrence status. METHODS: Between 2001 and 2013, patients who received hepatectomy for CLM and R-CLM were included in study. Patients with non-resectable R-CLM were excluded. RESULTS: One hundred sixteen patients were included: 86 patients in SH group and 30 patients in RH group. Repeat hepatectomy group had more synchronous CLM (76.7 versus 50 %, p = 0.011). From the 86 patients who underwent SH, 69 patients did not have R CLM. Survival analysis was done from the time of first hepatectomy for the no R CLM group and the time of RH for the RH group. The 3- and 5-year survival rates for the no R-CLM group were 66.4 and 48.8%, respectively, and for the RH group were 56 and 44.8% respectively (p = 0.841). Multivariate analysis showed that larger size of R-CLM is an independent risk factor for survival after RH. CONCLUSION: Repeat hepatectomy for R-CLM shows a comparable OS to non-recurrent CLM after single hepatectomy, despite the RH group had higher incidence of synchronous CLM. PMID- 26361775 TI - ORF2 protein of porcine circovirus type 2 promotes phagocytic activity of porcine macrophages by inhibiting proteasomal degradation of complement component 1, q subcomponent binding protein (C1QBP) through physical interaction. AB - Defining how each ORF of porcine circovirus type 2 (PCV2) manipulates the host immune system may be helpful to understand the disease progression of post weaning multisystemic wasting syndrome. In this study, we demonstrated a direct interaction between the PCV2 ORF2 and complement component 1, q subcomponent binding protein (C1QBP) within the cytoplasm of host macrophages. The physical interaction between PCV2 ORF2 and C1QBP inhibited ubiquitin-mediated proteasomal degradation of C1QBP in macrophages. Increased stability of C1QBP by the interaction with PCV2 ORF2 further enhanced the phagocytic activity of porcine macrophages through the phosphoinositol 3-kinase signalling pathway. This may explain the molecular basis of how PCV2 ORF2 enhances the phagocytic activity of host macrophages. PMID- 26361776 TI - Patient Satisfaction After Femoral Arterial Access Site Closure Using the ExoSeal((r)) Vascular Closure Device Compared to Manual Compression: A Prospective Intra-individual Comparative Study. AB - PURPOSE: To intra-individually compare discomfort levels and patient satisfaction after arterial access closure using the ExoSeal((r)) vascular closure device (VCD) and manual compression (MC) in a prospective study design. METHODS: Patients undergoing two planned interventions from 07/2013 to 09/2014 could participate in the study. Access closure was performed with an ExoSeal((r))-VCD in one and MC in the other intervention. Patients were clinically and sonographically examined and were given questionnaires 1 day after intervention [groin- and back-pain during bedrest (100-point visual analog scale; 0: no pain); comfortability of bedrest (10-point Likert scale, 1: comfortable), satisfaction with closure (10-point Likert scale, 1: very satisfied)]. Results were analyzed in a cross-over design. RESULTS: 48 patients (29 male, median age 62.5 (32-88) years) were included. An ExoSeal((r))-VCD was used first in 25 cases. As four of these subsequently refused MC as second intervention, data from 44 patients could be analyzed. All closures were technically successful (successful device deployment) without major complications. Groin- and back-pain after VCD-use/MC was 0 (0-15) vs. 10 (0-80) and 0 (0-75) vs. 25 (0-90), respectively (p < 0.0001). Bedrest after VCD-use was more comfortable than after MC [1 (range 1-7) vs. 6 (2 10); p < 0.0001]. Satisfaction with the closure procedure and with the intervention in general was higher after VCD-use compared to MC [1 (1-3) vs. 5 (2 10) and 1 (1-2) vs. 2 (1-4), respectively; p < 0.0001]. CONCLUSION: Intra individual comparison showed pain levels and discomfort to be significantly lower after ExoSeal((r)) use compared to MC. VCD closure was associated with higher satisfaction both with the closure itself and with the intervention in general. PMID- 26361777 TI - Identification of altered metabolic pathways of gamma-irradiated rice mutant via network-based transcriptome analysis. AB - In order to develop rice mutants for crop improvement, we applied gamma irradiation mutagenesis and selected a rice seed color mutant (MT) in the M14 targeting-induced local lesions in genome lines. This mutant exhibited differences in germination rate, plant height, and root length in seedlings compared to the wild-type plants. We found 1645 different expressed probes of MT by microarray hybridization. To identify the modified metabolic pathways, we conducted integrated genomic analysis such as weighted correlation network analysis with a module detection method of differentially expressed genes (DEGs) in MT on the basis of large-scale microarray transcriptional profiling. These modules are largely divided into three subnetworks and mainly exhibit overrepresented gene ontology functions such as oxidation-related function, ion binding, and kinase activity (phosphorylation), and the expressional coherences of module genes mainly exhibited in vegetative and maturation stages. Through a metabolic pathway analysis, we detected the significant DEGs involved in the major carbohydrate metabolism (starch degradation), protein degradation (aspartate protease), and signaling in sugars and nutrients. Furthermore, the accumulation of amino acids (asparagine and glutamic acid), sucrose, and starch in MT were affected by gamma rays. Our results provide an effective approach for identification of metabolic pathways associated with useful agronomic traits in mutation breeding. PMID- 26361779 TI - CORR Insights((r)): Factors Associated with Reoperation after Fixation of Displaced Olecranon Fractures. PMID- 26361778 TI - Cardiorespiratory fitness is a stronger indicator of cardiometabolic risk factors and risk prediction than self-reported physical activity levels. AB - This study investigated the relationships of self-reported physical activity levels and cardiorespiratory fitness in 81 males to assess which measurement is the greatest indicator of cardiometabolic risk. Physical activity levels were determined by the General Practice Physical Activity Questionnaire tool and cardiorespiratory fitness assessed using the Chester Step Test. Cardiovascular disease risk was estimated using the QRISK2, Framingham Lipids, Framingham body mass index and Joint British Societies' Guidelines-2 equations, and type 2 diabetes mellitus risk calculated using QDiabetes, Leicester Risk Assessment, Finnish Diabetes Risk Score and Cambridge Risk Score models. Categorising employees by cardiorespiratory fitness categories ('Excellent/Good' vs 'Average/Below Average') identified more differences in cardiometabolic risk factor (body mass index, waist circumference, total cholesterol, total cholesterol:high-density lipoprotein ratio, high-density lipoprotein cholesterol, triglycerides, HbA(1c)) scores than physical activity (waist circumference only). Cardiorespiratory fitness levels also demonstrated differences in all four type 2 diabetes mellitus risk prediction models and both the QRISK2 and Joint British Societies' Guidelines-2 cardiovascular disease equations. Furthermore, significant negative correlations (p < 0.001) were observed between individual cardiorespiratory fitness values and estimated risk in all prediction models. In conclusion, from this preliminary observational study, cardiorespiratory fitness levels reveal a greater number of associations with markers of cardiovascular disease or type 2 diabetes mellitus compared to physical activity determined by the General Practice Physical Activity Questionnaire tool. PMID- 26361780 TI - The effects of chronic administration of nandrolone decanoate on redox status in exercised rats. AB - For the past 40 years, anabolic-androgenic steroids have been used by a wide variety of athletes with the hope of improving their training, endurance, and performance. The aim of this study was to examine the chronic effects of nandrolone decanoate (20 mg/kg, s.c, Deca-Durabolin DECA((r))) on oxidative stress biomarkers in the hearts of sedentary and exercised rats. The male Wistar albino rats (n = 180, four groups with three subgroups, 15 per subgroup, age 10 weeks, body mass 200-220 g) were sacrificed, and in the collected samples of blood, the following markers of oxidative stress were measured spectrophotometrically: (1) index of lipid peroxidation (measured as TBARS thiobarbituric acid reactive substances); (2) nitrites (NO2 (-)); (3) hydrogen peroxide (H2O2); (4) superoxide anion radical (O2 (-)), and superoxide dismutase, catalase, and glutathione reductase. The results clearly show that the impact of ND alone, or in combination with physical training in general, is mildly pro oxidative. The chronic physical training probably induces the protective antioxidant enzyme system , which may be of clinical interest when faced with overdosage of this drug. PMID- 26361781 TI - The Proteolytic Systems of Muscle Wasting. AB - Skeletal muscle represents one of the most plastic tissues of our body thanks to the presence of heterogeneous population of myofibers that confer to skeletal muscle the functional plasticity necessary to modulate its morpho-fuctional properties in response to a wide range of external factors. Thus, alteration in fiber type composition represents a major component in muscle wasting associated with muscle diseases. Several mechanisms have been proposed to account for the alteration in the morpho-functional properties of skeletal muscle under pathological conditions. In this review we will discuss the potential catabolic mediators of muscle atrophy and wasting. PMID- 26361782 TI - What is an Odds Ratio? What does it mean? PMID- 26361783 TI - MPs may hold inquiry into safety of using antimalarial mefloquine in military. PMID- 26361784 TI - Characteristics of multidrug-resistant Acinetobacter baumannii strains isolated in Geneva during colonization or infection. AB - This study determined the antibiotic susceptibility profile and genetic mechanisms of beta-lactam resistance in 27 clinical strains of Acinetobacter baumannii isolated at the University Hospitals of Geneva, Switzerland. The antimicrobial susceptibility testing was performed using Etest and the disc diffusion method in accordance with CLSI guidelines. All of the strains were defined as multi-drug resistant (MDR) and were susceptible to colistin and moderately susceptible to tigecycline. Uniplex PCR assays were used to detect the following beta-lactamase genes: four class D carbapenem-hydrolysing oxacillinases (blaOXA-51, blaOXA-23, blaOXA-24 and blaOXA-58), four class B metallo-beta lactamases genes (blaIMP, blaVIM, blaSPM and blaNDM) and two class A carbapenemases (blaKPC and blaGES). All of the strains were positive for blaOXA 51 (intrinsic resistance), 14/27 strains carried blaOXA-23, 2/27 strains carried a blaOXA-24-like gene, and 4/27 strains had a blaOXA-58 gene. blaGES-11 was found in three strains, and NDM-1-harbouring strains were identified in three patients. All of the A. baumannii isolates were typed by rep-PCR (DiversiLab) and excluded any clonality. Altogether, this analysis suggests a very high genetic diversity of imported MDR A. baumannii. PMID- 26361785 TI - Apaf1 inhibition promotes cell recovery from apoptosis. AB - The protein apoptotic protease activating factor 1 (Apaf1) is the central component of the apoptosome, a multiprotein complex that activates procaspase-9 after cytochrome c release from the mitochondria in the intrinsic pathway of apoptosis. We have developed a vital method that allows fluorescence-activated cell sorting of cells at different stages of the apoptotic pathway and demonstrated that upon pharmacological inhibition of Apaf1, cells recover from doxorubicin- or hypoxia-induced early apoptosis to normal healthy cell. Inhibiting Apaf1 not only prevents procaspase-9 activation but delays massive mitochondrial damage allowing cell recovery. PMID- 26361786 TI - Mitochondrial haplogroup B increases the risk for hearing loss among the Eastern Asian pedigrees carrying 12S rRNA 1555A>G mutation. PMID- 26361787 TI - Pathway-based analysis for genome-wide association study data of bipolar disorder provides new insights for genetic study. PMID- 26361788 TI - The benefits of four weeks of melatonin treatment on circadian patterns in resistance-trained athletes. AB - Exercise can induce circadian phase shifts depending on the duration, intensity and frequency. These modifications are of special meaning in athletes during training and competition. Melatonin, which is produced by the pineal gland in a circadian manner, behaves as an endogenous rhythms synchronizer, and it is used as a supplement to promote resynchronization of altered circadian rhythms. In this study, we tested the effect of melatonin administration on the circadian system in athletes. Two groups of athletes were treated with 100 mg day(-1) of melatonin or placebo 30 min before bed for four weeks. Daily rhythm of salivary melatonin was measured before and after melatonin administration. Moreover, circadian variables, including wrist temperature (WT), motor activity and body position rhythmicity, were recorded during seven days before and seven days after melatonin or placebo treatment with the aid of specific sensors placed in the wrist and arm of each athlete. Before treatment, the athletes showed a phase shift delay of the melatonin circadian rhythm, with an acrophase at 05:00 h. Exercise induced a phase advance of the melatonin rhythm, restoring its acrophase accordingly to the chronotype of the athletes. Melatonin, but not placebo treatment, changed daily waveforms of WT, activity and position. These changes included a one-hour phase advance in the WT rhythm before bedtime, with a longer nocturnal steady state and a smaller reduction when arising at morning than the placebo group. Melatonin, but not placebo, also reduced the nocturnal activity and the activity and position during lunch/nap time. Together, these data reflect the beneficial effect of melatonin to modulate the circadian components of the sleep-wake cycle, improving sleep efficiency. PMID- 26361789 TI - Mass Gathering Medical Care. PMID- 26361790 TI - Individually modifiable risk factors to ameliorate cognitive aging: a systematic review and meta-analysis. AB - A number of health and lifestyle factors are thought to contribute to cognitive decline associated with age but cannot be easily modified by the individual patient. We identified 12 individually modifiable interventions that can be implemented during midlife or later with the potential to ameliorate cognitive aging. For ten of these, we used PubMed databases for a systematic review of long duration (at least 6 months), randomized, controlled trials in midlife and older adults without dementia or mild cognitive impairment with objective measures of neuropsychological performance. Using network meta-analysis, we performed a quantitative synthesis for global cognition (primary outcome) and episodic memory (secondary outcome). Of 1038 publications identified by our search strategy, 24 eligible trials were included in the network meta-analysis. Results suggested that the Mediterranean diet supplemented by olive oil and tai chi exercise may improve global cognition, and the Mediterranean diet plus olive oil and soy isoflavone supplements may improve memory. Effect sizes were no more than small (standardized mean differences 0.11-0.22). Cognitive training may have cognitive benefit as well. Most individually modifiable risk factors have not yet been adequately studied. We conclude that some interventions that can be self initiated by healthy midlife and older adults may ameliorate cognitive aging. PMID- 26361792 TI - Alexithymia and fertility-related stress. AB - The investigation of the relationship between alexithymia, the inability to identify and describe feelings and the absence of fantasies, and fertility related distress is a relatively neglected area of research. The aims of this study were to examine: (1) the prevalence of alexithymia in a sample of infertile women, and (2) the association between alexithymia, coping strategies, and fertility-related stress. This study included 160 infertile women undergoing in vitro fertilization in a public fertility clinic from September of 2013 to December of 2013. Self-report instruments were used to measure alexithymia (Toronto Alexithymia Scale-20), coping (COPE), and fertility-related stress (Fertility Problem Inventory). Bivariate and multiple linear regression were used. A high alexithymia score was positively associated with age, infertility duration, and low educational and economic level. Multivariate analyses showed that, controlling for demographic factors, high avoidance coping, low problem appraisal coping, and high alexithymia were positively associated with fertility related stress (beta = 0.309, p < .001, beta = -0.203, p = .006, beta = 0.151, p = .050, respectively). Results of this study indicated that alexithymia during fertility treatment was associated with maladaptive coping strategies and psychological stress. In addition, the association between alexithymia and duration of infertility may be interpreted as secondary alexithymia acts as a coping strategy in infertile women. PMID- 26361791 TI - Inhalation Exposure to Carbon Nanotubes (CNT) and Carbon Nanofibers (CNF): Methodology and Dosimetry. AB - Carbon nanotubes (CNT) and nanofibers (CNF) are used increasingly in a broad array of commercial products. Given current understandings, the most significant life-cycle exposures to CNT/CNF occur from inhalation when they become airborne at different stages of their life cycle, including workplace, use, and disposal. Increasing awareness of the importance of physicochemical properties as determinants of toxicity of CNT/CNF and existing difficulties in interpreting results of mostly acute rodent inhalation studies to date necessitate a reexamination of standardized inhalation testing guidelines. The current literature on pulmonary exposure to CNT/CNF and associated effects is summarized; recommendations and conclusions are provided that address test guideline modifications for rodent inhalation studies that will improve dosimetric extrapolation modeling for hazard and risk characterization based on the analysis of exposure-dose-response relationships. Several physicochemical parameters for CNT/CNF, including shape, state of agglomeration/aggregation, surface properties, impurities, and density, influence toxicity. This requires an evaluation of the correlation between structure and pulmonary responses. Inhalation, using whole body exposures of rodents, is recommended for acute to chronic pulmonary exposure studies. Dry powder generator methods for producing CNT/CNF aerosols are preferred, and specific instrumentation to measure mass, particle size and number distribution, and morphology in the exposure chambers are identified. Methods are discussed for establishing experimental exposure concentrations that correlate with realistic human exposures, such that unrealistically high experimental concentrations need to be identified that induce effects under mechanisms that are not relevant for workplace exposures. Recommendations for anchoring data to results seen for positive and negative benchmark materials are included, as well as periods for postexposure observation. A minimum data set of specific bronchoalveolar lavage parameters is recommended. Retained lung burden data need to be gathered such that exposure-dose-response correlations may be analyzed and potency comparisons between materials and mammalian species are obtained considering dose metric parameters for interpretation of results. Finally, a list of research needs is presented to fill data gaps for further improving design, analysis, and interpretation and extrapolation of results of rodent inhalation studies to refine meaningful risk assessments for humans. PMID- 26361793 TI - Overexpression and knockout of miR-126 both promote leukemogenesis. AB - It is generally assumed that gain- and loss-of-function manipulations of a functionally important gene should lead to the opposite phenotypes. We show in this study that both overexpression and knockout of microRNA (miR)-126 surprisingly result in enhanced leukemogenesis in cooperation with the t(8;21) fusion genes AML1-ETO/RUNX1-RUNX1T1 and AML1-ETO9a (a potent oncogenic isoform of AML1-ETO). In accordance with our observation that increased expression of miR 126 is associated with unfavorable survival in patients with t(8;21) acute myeloid leukemia (AML), we show that miR-126 overexpression exhibits a stronger effect on long-term survival and progression of AML1-ETO9a-mediated leukemia stem cells/leukemia initiating cells (LSCs/LICs) in mice than does miR-126 knockout. Furthermore, miR-126 knockout substantially enhances responsiveness of leukemia cells to standard chemotherapy. Mechanistically, miR-126 overexpression activates genes that are highly expressed in LSCs/LICs and/or primitive hematopoietic stem/progenitor cells, likely through targeting ERRFI1 and SPRED1, whereas miR 126 knockout activates genes that are highly expressed in committed, more differentiated hematopoietic progenitor cells, presumably through inducing FZD7 expression. Our data demonstrate that miR-126 plays a critical but 2-faceted role in leukemia and thereby uncover a new layer of miRNA regulation in cancer. Moreover, because miR-126 depletion can sensitize AML cells to standard chemotherapy, our data also suggest that miR-126 represents a promising therapeutic target. PMID- 26361795 TI - Effect of high-dose phytase and citric acid, alone or in combination, on growth performance of broilers given diets severely limited in available phosphorus. AB - 1. Two trials were conducted to evaluate the effect of high-dose phytase alone or in combination with citric acid (CA) in the diet severely limited in available phosphorus (P) on performance, plasma P and plasma Ca of broilers from 22 to 42 d of age. 2. In Trial 1, 297 21-d-old female chicks were placed into 27 pens and allocated to 9 maize-soybean meal-based dietary treatments, which were a positive control [PC, 4.23 g/kg non-phytate P (NPP)] and 8 negative control (NC, 1.35 g/kg NPP) groups consisting of two concentrations of CA (0 and 20 g/kg) and 4 concentrations of phytase (0, 1000, 2000 and 4000 U/kg) in a 2 * 4 factorial arrangement. In Trial 2, 192 21-d-old male chicks were placed into 24 pens and allocated to 6 wheat-canola meal-based dietary treatments, which were a PC (4.2 g/kg NPP), a NC (1.68 g/kg NPP) and 4 NC groups consisting of two concentrations of CA (0 and 20 g/kg) and two concentrations of phytase (2000 and 4000 U/kg) in a 2 * 2 factorial arrangement. 3. In both trials, birds fed on the PC had significantly higher average daily gain (ADG), average daily feed intake (ADFI), plasma P and lower feed conversion ratio (FCR) and plasma Ca than those of birds fed on the NC. CA supplementation significantly increased ADG and ADFI. There was a significant interaction between CA and phytase on plasma P where CA improved the effect of phytase on plasma P. In Trial 1, phytase addition improved ADG, ADFI, FCR and plasma Ca linearly. 4. Briefly, this research showed the interaction effect between CA and phytase on plasma P when broilers were fed on diets based on maize-soybean meal or wheat-canola meal. The results showed that CA supplementation lowered the concentration of phytase that is needed in low NPP diets to increase plasma P. PMID- 26361794 TI - Treatment and survival among 1594 patients with ATL. AB - Adult T-cell leukemia/lymphoma (ATL) is a malignancy of mature T lymphocytes caused by human T-lymphotropic virus type I. Intensive combination chemotherapy and allogeneic hematopoietic stem cell transplantation have been introduced since the previous Japanese nationwide survey was performed in the late 1980s. In this study, we delineated the current features and management of ATL in Japan. The clinical data were collected retrospectively from the medical records of patients diagnosed with ATL between 2000 and 2009, and a total of 1665 patients' records were submitted to the central office from 84 institutions in Japan. Seventy-one patients were excluded; 895, 355, 187, and 157 patients with acute, lymphoma, chronic, and smoldering types, respectively, remained. The median survival times were 8.3, 10.6, 31.5, and 55.0 months, and 4-year overall survival (OS) rates were 11%, 16%, 36%, and 52%, respectively, for acute, lymphoma, chronic, and smoldering types. The number of patients with allogeneic hematopoietic stem cell transplantation was 227, and their median survival time and OS at 4 years after allogeneic hematopoietic stem cell transplantation was 5.9 months and 26%, respectively. This study revealed that the prognoses of the patients with acute and lymphoma types were still unsatisfactory, despite the recent progress in treatment modalities, but an improvement of 4-year OS was observed in comparison with the previous survey. Of note, one-quarter of patients who could undergo transplantation experienced long survival. It is also noted that the prognosis of the smoldering type was worse than expected. PMID- 26361796 TI - Mining the Archives: A Cross-Platform Analysis of Gene Expression Profiles in Archival Formalin-Fixed Paraffin-Embedded Tissues. AB - Formalin-fixed paraffin-embedded (FFPE) tissue samples represent a potentially invaluable resource for transcriptomic research. However, use of FFPE samples in genomic studies has been limited by technical challenges resulting from nucleic acid degradation. Here we evaluated gene expression profiles derived from fresh frozen (FRO) and FFPE mouse liver tissues preserved in formalin for different amounts of time using 2 DNA microarray protocols and 2 whole-transcriptome sequencing (RNA-seq) library preparation methodologies. The ribo-depletion protocol outperformed the other methods by having the highest correlations of differentially expressed genes (DEGs), and best overlap of pathways, between FRO and FFPE groups. The effect of sample time in formalin (18 h or 3 weeks) on gene expression profiles indicated that test article treatment, not preservation method, was the main driver of gene expression profiles. Meta- and pathway analyses indicated that biological responses were generally consistent for 18 h and 3 week FFPE samples compared with FRO samples. However, clear erosion of signal intensity with time in formalin was evident, and DEG numbers differed by platform and preservation method. Lastly, we investigated the effect of time in paraffin on genomic profiles. Ribo-depletion RNA-seq analysis of 8-, 19-, and 26 year-old control blocks resulted in comparable quality metrics, including expected distributions of mapped reads to exonic, untranslated region, intronic, and ribosomal fractions of the transcriptome. Overall, our results indicate that FFPE samples are appropriate for use in genomic studies in which frozen samples are not available, and that ribo-depletion RNA-seq is the preferred method for this type of analysis in archival and long-aged FFPE samples. PMID- 26361797 TI - Sulfenic Acid Modification of Endothelin B Receptor is Responsible for the Benefit of a Nonsteroidal Mineralocorticoid Receptor Antagonist in Renal Ischemia. AB - AKI is associated with high mortality rates and the development of CKD. Ischemia/reperfusion (IR) is an important cause of AKI. Unfortunately, there is no available pharmacologic approach to prevent or limit renal IR injury in common clinical practice. Renal IR is characterized by diminished nitric oxide bioavailability and reduced renal blood flow; however, the mechanisms leading to these alterations are poorly understood. In a rat model of renal IR, we investigated whether the administration of the novel nonsteroidal mineralocorticoid receptor (MR) antagonist BR-4628 can prevent or treat the renal dysfunction and tubular injury induced by IR. Renal injury induced by ischemia was associated with increased oxidant damage, which led to a cysteine sulfenic acid modification in endothelin B receptor and consequently decreased endothelial nitric oxide synthase activation. These modifications were efficiently prevented by nonsteroidal MR antagonism. Furthermore, we demonstrated that the protective effect of BR-4628 against IR was lost when a selective endothelin B receptor antagonist was coadministered. These data describe a new mechanism for reduced endothelial nitric oxide synthase activation during renal IR that can be blocked by MR antagonism with BR-4628. PMID- 26361798 TI - Mineralocorticoid Receptor Antagonism in AKI: A New Hope? PMID- 26361799 TI - Dense Deposit Disease Mimicking a Renal Small Vessel Vasculitis. AB - Dense deposit disease is caused by fluid-phase dysregulation of the alternative complement pathway and frequently deviates from the classic membranoproliferative pattern of injury on light microscopy. Other patterns of injury described for dense deposit disease include mesangioproliferative, acute proliferative/exudative, and crescentic GN. Regardless of the histologic pattern, C3 glomerulopathy, which includes dense deposit disease and C3 GN, is defined by immunofluorescence intensity of C3c two or more orders of magnitude greater than any other immune reactant (on a 0-3 scale). Ultrastructural appearances distinguish dense deposit disease and C3 GN. Focal and segmental necrotizing glomerular lesions with crescents, mimicking a small vessel vasculitis such as ANCA-associated GN, are a very rare manifestation of dense deposit disease. We describe our experience with this unusual histologic presentation and distinct clinical course of dense deposit disease, discuss the pitfalls in diagnosis, examine differential diagnoses, and review the relevant literature. PMID- 26361800 TI - Cell-cycle arrest biomarkers: the light at the end of the acute kidney injury tunnel. PMID- 26361801 TI - The changing trends and outcomes in renal replacement therapy: data from the ERA EDTA Registry. AB - BACKGROUND: This study examines the time trends in incidence, prevalence, patient and kidney allograft survival and causes of death (COD) in patients receiving renal replacement therapy (RRT) in Europe. METHODS: Eighteen national or regional renal registries providing data to the European Renal Association-European Dialysis and Transplant Association Registry between 1998 and 2011 were included. Incidence and prevalence time trends between 2001 and 2011 were studied with Joinpoint and Poisson regression. Patient and kidney allograft survival and COD between 1998 and 2011 were analysed using Kaplan-Meier and competing risk methods and Cox regression. RESULTS: From 2001 to 2008, the adjusted incidence of RRT rose by 1.1% (95% CI: 0.6, 1.7) annually to 131 per million population (pmp). During 2008-2011, the adjusted incidence fell by 2.2% (95% CI: -4.2, -0.2) annually to 125 pmp. This decline occurred predominantly in patients aged 45-64 years, 65-74 years and in the primary renal diseases diabetes mellitus type 1 and 2, renovascular disease and glomerulonephritis. Between 2001 and 2011, the overall adjusted prevalence increased from 724 to 1032 pmp (+3.3% annually, 95% CI: 2.8, 3.8). The adjusted 5-year patient survival on RRT improved between 1998 2002 and 2003-2007 [adjusted hazard ratio (HRa) 0.85, 95% CI: 0.84, 0.86]. Comparing these time periods, the risk of cardiovascular deaths fell by 25% (HRa 0.75, 95% CI: 0.74, 0.77). However the risk of malignant death rose by 9% (HRa 1.09, 95% CI: 1.03, 1.16) in patients >=65 years. CONCLUSION: This European study shows a declining RRT incidence, particularly in patients aged 45-64 years, 65-74 years and secondary to diabetic nephropathy. Encouragingly, the adjusted RRT patient survival continues to improve. The risk of cardiovascular death has decreased, though the risk of death from malignancy has increased in the older population. PMID- 26361802 TI - Estrogen or anti-estrogen for Bologna poor responders? AB - The current study aims to compare cycle outcomes of two ovarian stimulation protocols in poor responders according to the Bologna criteria; luteal estrogen priming (LE) or letrozole (LZ) co-treatment in antagonist protocol. Following retrospective chart review of a single center, 162 cycles were found eligible for the comparison of two ovarian stimulation protocols. After interpreting data, significantly higher serum estradiol levels, longer duration of cycle, higher number of fertilized oocytes and good quality embryos were detected in patients who received LE. Despite any statistical significance, higher clinical pregnancy rate (CPR) and ongoing pregnancy rate (OPR) per embryo transfer (ET) were detected with LE protocol compared with LZ (12.3% versus 18.2% and 9.6% versus 12.7%, respectively). Younger patients (<40 years) revealed higher CPR and OPR per started cycle compared with older patients (>=40 years) where only OPR was statistically significant. Multivariable analysis demonstrated that basal antral follicle count, peak serum estradiol levels and number of fertilized oocytes were independent variables significantly associated with clinical pregnancies (p < 0.05). In the current analysis, LE or LZ protocols revealed comparable but quite low pregnancy rates in poor responders according to the Bologna criteria. Younger patients were more likely to achieve pregnancy compared to older patients with both protocols. PMID- 26361803 TI - Unusual intrabony transmigration of mandibular canine: case series (report of 4 cases). AB - Intrabony cross arch migration (transmigration) of impacted teeth is a very rare dental anomaly. Transmigration is commonly seen in permanent dentition of the lower jaw. The tooth most commonly involved is the mandibular canine. The prevalence of transmigrated canine has been found to be only 0.14-0.31%. Transmigration of the canine most frequently occurs in a mesial direction resulting in migration across the mandibular symphysis to the opposite side of the dental arch. We report a case series (4 cases) of rare transmigration of mandibular canines and emphasise the need to use panoramic radiography in cases presenting with either over retained deciduous canines and/or missing permanent canines. We also propose a newer modification to the present classification of transmigration for one of these cases as the present classification does not include all the entities. PMID- 26361804 TI - Concurrent intracerebral and intramedullary spinal tuberculomas in an immunocompetent individual. PMID- 26361806 TI - Rheumatic heart disease. PMID- 26361805 TI - Dermatomyositis onset in the puerperium period. AB - Dermatomyositis is rare during the reproductive period, but when it does occur, most cases have been reported from the viewpoint of the obstetric management of high-risk pregnancy. In return, there is little information concerning the contribution of pregnancy to the development and course of dermatomyositis. We describe a patient with dermatomyositis that presented after the delivery of a healthy infant. This case, with support from a literature review, suggests that pregnancy could be a trigger or contributor for the development of dermatomyositis. PMID- 26361807 TI - A circumaortic left renal vein. PMID- 26361808 TI - Flexural behavior of PEEK materials for dental application. AB - OBJECTIVES: The high-performance thermoplastic polymer PEEK (poly-ether-ether ketone) is used as alternative implant material to metals since 1998 in many medical fields due to its bone-like mechanical properties. These iso-elastic characteristics of PEEK lead to the assumption, that it could represent a viable alternative to conventional materials also in the field of dentistry. Therefore the mechanical properties of different PEEK-compounds should be eavuated vie the three-point bending test. METHODS: 150 specimens of 11 different PEEK-compounds were tested via a three-point bending test using a universal testing machine (Z010, Zwick GmbH & Co, Ulm, Germany) after dry storage on the one hand and after incubation at 37 degrees C in Ringer solution (Fa. Braun Melsungen AG, Melsungen, Deutschland) for one day, 7 days, 28 days und 84 days on the other hand and the material parameters bending modulus and bending strength were evaluated. RESULTS: The results regarding the bending moduli ranged from 2.73+/-0.26GPa for an unfilled brand to 47.27+/-10.3GPa for a carbon fiber reinforced PEEK with unidirectional continuous carbon fibers. Accordingly the bending strengths of these two material types ranged from 170.37+/-19.31MPa to 1009.63+/-107.33MPa. SIGNIFICANCE: All tested specimens showed higher values than the prevailing minimum strength for plastic materials and their application in dentistry of 65MPa (DIN EN ISO 10477). This underlines the applicability of PEEK in dentistry and points out the possibility to offer patients metal free restorations, especially in the presence of allergies and/or bruxism. PMID- 26361809 TI - Conversion, shrinkage, water sorption, flexural strength and modulus of re mineralizing dental composites. AB - OBJECTIVES: Cure, volumetric changes and mechanical properties were assessed for new dental composites containing chlorhexidine (CHX) and reactive calcium phosphate-containing (CaP) to reduce recurrent caries. METHODS: 20wt.% of light curable urethane dimethacrylate based liquid was mixed with 80wt.% glass filler containing 10wt.% CHX and 0-40wt.% CaP. Conversion versus depth with 20 or 40s light exposure was assessed by FTIR. Solidification depth and polymerization shrinkage were determined using ISO 4049 and 17304, respectively. Subsequent volume expansion and biaxial flexural strength and modulus change upon water immersion were determined over 4 weeks. Hydroxyapatite precipitation in simulated body fluid was assessed at 1 week. RESULTS: Conversion decreased linearly with both depth and CaP content. Average solidification depths were 4.5, 3.9, 3.3, 2.9 and 5.0 with 0, 10, 20, and 40% CaP and a commercial composite, Z250, respectively. Conversions at these depths were 53+/-2% for experimental materials but with Z250 only 32%. With Z250 more than 50% conversion was achieved only below 1.1mm. Shrinkage was 3% and 2.5% for experimental materials and Z250, respectively. Early water sorption increased linearly, whilst strength and modulus decreased exponentially to final values when plotted versus square root of time. Maximum volumetric expansion increased linearly with CaP rise and balanced shrinkage at 10-20wt.% CaP. Strength and modulus for Z250 decreased from 191 to 158MPa and 3.2 to 2.5GPa. Experimental composites initial strength and modulus decreased linearly from 169 to 139MPa and 5.8 to 3.8GPa with increasing CaP. Extrapolated final values decreased from 156 to 84MPa and 4.1 to 1.7GPa. All materials containing CaP promoted hydroxyapatite precipitation. SIGNIFICANCE: The lower surface of composite restorations should both be solid and have greater than 50% conversion. The results, therefore, suggest the experimental composite may be placed in much thicker layers than Z250 and have reduced unbounded cytotoxic monomer. Experimental materials with 10-20wt.% additionally have volumetric expansion to compensate shrinkage, antibacterial and re-mineralizing components and competitive mechanical properties. PMID- 26361810 TI - Randomized, placebo-controlled study of the efficacy of a calcium phosphate containing paste on dentin hypersensitivity. AB - OBJECTIVE: Hypersensitivity of non-carious cervical lesions (DH) is a frequently encountered disease. This randomized, controlled, single-blind crossover study evaluated the effectiveness of a calcium phosphate containing desensitizer paste (TAP) on DH in comparison to water as placebo (PLA). METHODS: In this clinical trial 35 patients were randomly assigned to the test and the negative control group. Using a 10cm long VAS (visual analog scale) patients should respond with DH score >6 on one tooth in each of two quadrants for allocation. Pain stimuli were a 2-seconds air blast (AB) and probe scratching (PS) of the exposed dentin. VAS scores were determined pre-operatively (PRE), immediately after treatment (POST), at 1 week, 1, 3 and finally after 6 months. RESULTS: Both TAP and PLA applications decreased DH significantly at POST and throughout the 6-months recalls (p<0.001). Pain reductions upon AB stimulation of TAP treated teeth, assessed at POST and 6 months were 35 and 55%, upon PS stimuli 21 and 54%, respectively. PLA treated lesions responded to AB at POST and after 6 months with 20 and 36% pain reduction, to PS with 11 and 30% pain reduction, respectively. Differences between TAP and PLA pain scores were statistically significant at all recalls (p<0.05). SIGNIFICANCE: TAP paste reduced DH successfully during this 6 months trial. The calcium phosphate crystallites included in the paste and the presumed hydroxyapatite precipitates upon exposure to saliva were hypothetically able to occlude open dentinal tubules, at least to some extent. TAP is considered a biocompatible desensitizer paste. PMID- 26361812 TI - Public sector physiotherapists believe that staff supervision should be broad ranging, individualised, structured, and based on needs and goals: a qualitative study. AB - QUESTION: What do physiotherapists consider to be the structure and content of an effective clinical supervision program for public sector staff? DESIGN: Qualitative study using emergent-systematic focus group design. PARTICIPANTS: 46 physiotherapists and six physiotherapy assistants from a large, regional, Australian health service participated in one of seven focus groups. RESULTS: Data were represented by three major categories: the content of supervision; the structure of supervision; and participants' roles and attributes. The content of supervision should encompass all issues affecting workplace experience and performance; supervision should be individualised and needs based. For the structure of supervision, a variety of methods and formats should be available, including: scheduled and unscheduled supervision (unscheduled supervision addresses needs as they arise but its usefulness can be restricted by supervisor availability); the environment should be organised to facilitate supervision; supervision should be integrated into existing practices; and supervision should be adequately prioritised and resourced to enable sustainability. In relation to participants' roles and attributes, respondents recommended: clearly defined supervisor and supervisee roles, responsibilities, skills and attributes are required to facilitate a constructive relationship on which successful supervision depends; the supervisee should take primary responsibility for leading and organising their supervision; the supervisor provides support and accountability and assists with goal setting and attainment; and successful supervision requires considerable knowledge and skills from the supervisee and supervisor (supervision education and training might be necessary). CONCLUSION: The physiotherapists' perspectives that were identified in this study are important to consider when assessing current clinical supervision models, as well as when designing and implementing effective physiotherapy supervision programs. PMID- 26361813 TI - Asthma. PMID- 26361811 TI - Impact of diabetes mellitus and its complications: survival and quality-of-life in critically ill patients. AB - PURPOSE: Diabetes mellitus represents an increasing problem for patients and health care systems worldwide. We sought to investigate the effect of diabetes and its associated comorbidities on long-term survival and quality of life following an admission to a medical intensive care unit (ICU). METHODS: A total of 6662 consecutive patients admitted to ICU between 2004 and 2009 were included (patients with diabetes n=796, non-diabetic patients n=5866). The primary endpoint of the study was death of any cause. Data on mortality was collected upon review of medical records or phone interviews. Moreover, a questionnaire was sent to 500 randomly selected patients addressing Health related Quality of Life (HrQoL) after ICU treatment. RESULTS: Overall mortality did not differ significantly between diabetic and non-diabetic patients after ICU treatment (mean follow-up time: 490 days). For a subgroup of patients already exhibiting comorbidities associated with diabetes, the mortality rate was significantly higher (p=0.022). Regarding quality of life, no differences were found between groups. CONCLUSIONS: Diabetes was not associated with increased mortality or reduced quality of life in a general population of medical ICU patients. However, once comorbidities associated with diabetes occurred, the survival rate of patients with comorbidities associated with hyperglycemia was significantly reduced. PMID- 26361814 TI - A patient education program supported by staff training can reduce the rate of falls for older patients during inpatient rehabilitation [synopsis]. PMID- 26361815 TI - Parkinson's disease. PMID- 26361816 TI - Physiotherapy management of lateral epicondylalgia. PMID- 26361817 TI - The Wearable Cardioverter Defibrillator: an Early Single Centre Australian Experience. Some Pitfalls and Caveats for Use. AB - BACKGROUND: Wearable Cardioverter Defibrillators (WCD) have been effectively used for more than a decade in North America and Europe for prevention of sudden cardiac death (SCD) due to ventricular arrhythmias. This device has only recently been available in Australia. METHOD: At Westmead hospital, WCD has been used since 2013 as a bridging therapy to an implantable cardioverter defibrillator (ICD) for those at high risk, but are temporarily not suitable for an implantable device. Indications for use were explanted infected ICD, dilated cardiomyopathy, post partum cardiomyopathy, valvular heart disease and myocarditis. The default device settings were: ventricular tachycardia (VT) and ventricular fibrillation (VF) threshold of 150 bpm and 200 bpm respectively and response times were 60 secs for VT and 25 secs for VF. OUTCOME: WCD was used in eight patients. Duration of use ranged from five to 180 days with median of 77 days. Daily usage averaged 23.4+/-0.6hours. All except one were compliant with the device and none of our patients received shock or died during device usage. Four of the eight patients received ICD, two declined ICD, one was judged to no longer require ICD and one remains under assessment. CONCLUSION: WCD is easy to use, well tolerated and is effective for SCD prevention in patients who are temporarily not suitable for ICD. However patients need to be actively followed-up to reduce the duration of WCD usage and thereby be cost effective. PMID- 26361818 TI - Pre - Transcatheter Aortic Valve Implantation Workup in the Cardiac Catheterisation Laboratory. AB - Transcatheter aortic valve implantation (TAVI) is a rapidly evolving field with exponential growth worldwide in TAVI numbers. One of the principle methods in improving outcomes with a new technique such as TAVI is to ensure that patients undergo efficient pre-procedural evaluation. Standard TAVI workup includes clinical assessment, surgical and frailty risk scoring, blood investigations, echocardiography, pulmonary function tests, computed tomography (CT) angiography and cardiac catheterisation. Patients sent to the cardiac catheterisation laboratory (CCL) for TAVI workup require a systematic and thorough approach. This can include iliofemoral angiography, aortography, aortic valve crossing, haemodynamic evaluation, coronary angiography and right heart catheterisation. In addition, several key steps are required to evaluate suitability for the percutaneous transfemoral TAVI approach. This is the first review to systematically describe steps to evaluate pre-TAVI patients in the CCL. Due to the rapidly rising TAVI numbers, this workup will likely be performed not only by TAVI operators but also by the general interventional cardiologist. PMID- 26361819 TI - Re: Does Frailty Lie in the Eyes of the Beholder? PMID- 26361820 TI - A simple and inexpensive method to control oxygen concentrations within physiological and neoplastic ranges. AB - Traditional methods for regulating oxygen concentration ([O2]) in in vitro experiments over the range found in normal and tumor tissues require the use of expensive equipment to generate controlled gas atmospheres or the purchase of a range of gas cylinders with certified O2 percentages. Here we describe a simple and inexpensive enzymatic method for generating low, precise steady-state [O2] levels that are stable for several hours. This method is particularly applicable to the in vitro study of some classes of hypoxia-targeted antitumor prodrugs and bioreductively activated agents. PMID- 26361821 TI - Incidence and treatment costs attributable to medication errors in hospitalized patients. AB - BACKGROUND: A significant financial burden arises from medication errors that cause direct injury and those without patient harm that represent waste and inefficiency. OBJECTIVE: To estimate the incidence, types, and causes of medication errors as well as their attributable costs in a hospital setting. METHODS: For a retrospective case-control study, data were collected for 57,554 patients admitted to two New Jersey (U.S. State) hospitals during 2005-2006 as well as hospital-specific voluntary error reports from these two hospitals for the same period. Medication errors were classified into categories of stage, error type, and proximal cause, and the incidence was estimated. The costs attributable to medication errors were calculated using both the recycled prediction method, and the Blinder-Oaxaca decomposition method after propensity score matching. RESULTS: Medication errors occurred at a rate of 0.8 per 100 admissions, or 1.6 per 1000 patient days. Most errors occurred at the administration stage of the medication use process. The most frequent types of errors were wrong time, wrong medication, wrong dose, and omission errors. Treatment costs attributable to medication errors were in the range of $8,439 using the Blinder-Oaxaca decomposition method and $8,898 using the recycled prediction method. CONCLUSIONS: Medication errors are associated with significant additional costs, even without patient harm. Considering the substantial costs associated with adverse drug events, the elimination of medication errors should be further emphasized and promoted, and guidelines should be developed to facilitate this goal. PMID- 26361822 TI - Implementation of the American Diabetes Association's Standards of Medical Care post-Medicare Part D: The case of statin utilization in the elderly with diabetes. AB - BACKGROUND: The American Diabetes Association's (ADA's) Standards of Medical Care in Diabetes for statin use have changed to be driven by risk status rather than low-density lipoprotein cholesterol level. OBJECTIVES: The objectives of this study were to 1) examine how statins were used by risk status in elderly diabetics for whom they are recommended by the ADA's Standards with high levels of evidence, and 2) identify potential predictors of statin non-use using data containing Medicare Part D information in understanding how to further align patient care with the ADA's Standards. METHODS: This study was a pooled cross sectional study of the Medicare Current Beneficiaries Survey from 2006 to 2010. Sampling weights were applied to generate national estimates. Weighted logistic regression was performed to identify potential predicators of statin non-use. RESULTS: Between 2006 and 2010, 53.96%, 52.14%, 52.28%, 57.74%, and 59.81% of eligible diabetics used statins, respectively. About 70% of the patients with overt cardiovascular disease (CVD) took statins while only about 50% of those with CVD risk factors used statins in 2010. Compared to those with overt CVD, patients with CVD risk factors were less likely to take statins (OR: 0.56; 95% CI: 0.48-0.64). Other non-use predictors included: non-Hispanic Black, non metropolitan areas, and comorbidities. CONCLUSIONS: Implementation of the ADA's statin recommendations increased over the study period. Statin use differed significantly by patients' risk status. Future ADA's Standards focusing on how to improve utilization of statins for individuals with different risk status, particularly those with CVD risk factors but without overt CVD, are warranted. PMID- 26361823 TI - Pediatric Obesity: Pharmacokinetics and Implications for Drug Dosing. AB - PURPOSE: Clinicians are increasingly likely to have under their care obese children with diseases requiring pharmacotherapy. Optimal drug dosing for this population is unclear. Excess weight likely leads to alterations in pharmacokinetics. The purpose of this article was to describe the pharmacokinetics and pharmacodynamics in overweight and obese children and, where possible, provide recommendations for drug dosing. METHODS: EMBASE (1980-May 2015), MEDLINE (1950-May 2015), and International Pharmaceutical Abstracts (1970 May 2015) databases were searched by using the following terms: obesity, morbid obesity, overweight, pharmacokinetics, pharmacodynamics, drug, dose, drug levels, pediatric, and child. The search was limited to English-language articles. References of relevant articles were searched to identify additional studies. FINDINGS: Total body weight (TBW) is an appropriate size descriptor for dosing antineoplastic agents, succinylcholine, and cefazolin. Obese children seem to require less heparin, enoxaparin, and warfarin per kilogram TBW than normal weight children; providing standard adult doses may be insufficient, however. Obese children may also require less vancomycin and aminoglycosides per kilogram TBW than normal-weight children. For these medications, an alternate size descriptor in children has not been described, and initial dosing based on TBW and monitoring serum concentrations (vancomycin and aminoglycosides) or coagulation parameters (heparin, enoxaparin, and warfarin) is warranted. Obese children require less propofol than normal-weight children; however, there is limited information about the dosing of other anesthetics or opioids. IMPLICATIONS: Limitations to the available data include the inherent design constraints to case reports and retrospective cohort studies, as well as the small numbers of children in some of the studies. Use of normal-weight historical control subjects for obese children in the context of a pharmacokinetic study is not ideal. Although more information is becoming available, our understanding of the pharmacokinetics in obese children is still limited. When dosing information is not available for obese children, it may be necessary to extrapolate from available data in obese adults, but one should consider the effects of the child's age on pharmacokinetics. PMID- 26361824 TI - Inhibitor versus chaperone behaviour of d-fagomine, DAB and LAB sp(2)-iminosugar conjugates against glycosidases: A structure-activity relationship study in Gaucher fibroblasts. AB - A library of sp(2)-iminosugar conjugates derived from the piperidine iminosugar d fagomine and the enantiomeric pyrrolidine iminosugars DAB and LAB has been generated in only two steps involving direct coupling of the fully unprotected polyhydroxylated heterocycles with isothiocyanates, to give monocyclic thiourea adducts, and further intramolecular nucleophilic displacement of the delta located primary hydroxyl group by the thiocarbonyl sulphur atom, affording bicyclic isothioureas. These transformations led to a dramatic shift in the inhibitory selectivity from alpha- to beta-glucosidases, with inhibition potencies that depended strongly on the nature of the aglycone-type moiety in the conjugates. Some of the new derivatives behaved as potent inhibitors of human beta-glucocerebrosidase (GCase), the lysosomal enzyme whose dysfunction is responsible for Gaucher disease. Moreover, GCase inhibition was 10-fold weaker at pH 5 as compared to pH 7, which is generally considered as a good property for pharmacological chaperones. Surprisingly, most of the compounds strongly inhibited GCase in wild type fibroblasts at rather low concentrations, showing an unfavourable chaperone/inhibitor balance on disease-associated GCase mutants in cellulo. A structure-activity relationship analysis points to the need for keeping a contiguous triol system in the glycone moiety of the conjugates to elicit a chaperone effect. In any case, the results reported here represent a proof of concept of the utmost importance of implementing diversity-oriented strategies for the identification and optimization of potent and specific glycosidase inhibitors and chaperones. PMID- 26361825 TI - Variations in Medications and Prognosis of Heart Failure With Preserved Versus Reduced Ejection Fraction. PMID- 26361826 TI - Meta-Analysis of the Relation of Ventricular Arrhythmias to All-Cause Mortality After Implantation of a Left Ventricular Assist Device. AB - Ventricular arrhythmias (VAs) are commonly reported after implantation of left ventricular assist devices (LVADs). Their relation to all-cause mortality and potential risk factors remains unclear. We conducted a meta-analysis of observational studies with the primary objective of evaluating the association of post-LVAD VAs with all-cause mortality at 60, 120, and 180 days. The secondary end point was the association of potential risk factors (cause of cardiomyopathy, indication for LVAD, and history of VA) with mortality in patients with post-LVAD VAs. We searched MEDLINE, Embase, and Cochrane Central from 2001 to 2015. Two reviewers independently searched, selected, and assessed quality of included studies with differences resolved by consensus. Data were collected and analyzed using random- and fixed-effect model, as appropriate, with inverse-variance weighting. Of 2,393 studies identified, 9 observational studies were eligible including 1,179 patients with a mean follow-up of 220 days. Post-LVAD VAs were associated with increased risk of all-cause mortality after adjusting for competing risk factors at 60 days (adjusted odds ratio [OR] 1.91, 95% confidence interval [CI] 1.18 to 3.11, p = 0.001), 120 days (adjusted OR 1.97, 95% CI 1.01 to 3.85, p = 0.05), and 180 days (adjusted OR 2.04, 95% CI 1.01 to 4.15, p = 0.05). Using meta-regression analysis, it was found that only history of VA was a risk factor for mortality after LVAD implantation. In conclusion, post-LVAD VA is associated with an increased risk of all-cause mortality with pre-LVAD VAs acting as a risk factor. This meta-analysis, despite being only hypothesis generating, sets the stage for prospective collection of VA information in a prospective device trial or in the Interagency Registry for Mechanically Assisted Circulatory Support. PMID- 26361827 TI - Exercise Electrocardiogram Stress Testing for Evaluation of Chest Pain. PMID- 26361829 TI - Insight into "public" reporting of percutaneous coronary interventions in the state of Pennsylvania. PMID- 26361828 TI - Interplay Between Adiponectin and Pro-Atrial Natriuretic Peptide and Prognosis in Patients With ST-Segment Elevation Myocardial Infarction. AB - Natriuretic peptides (NPs) may regulate adipocyte metabolism including adiponectin. Infusion of atrial natriuretic peptide (ANP) increases plasma adiponectin in patients with heart failure. However, this relation has not been examined in a clinical setting or in myocardial infarction (MI). Accordingly, we investigated the interplay between proANP and adiponectin and the prognostic implications in patients with MI. We prospectively included 680 patients with ST segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention from September 2006 to December 2008. Blood samples were drawn immediately before percutaneous coronary intervention. Additionally, we included 40 patients with 4 obtained blood samples during STEMI. Adiponectin and proANP were measured in all plasma samples. All patients were followed for 5 years. End points were all-cause mortality (n = 137) and the combined end point (n = 170) of major adverse cardiovascular events (MACEs). Plasma adiponectin and proANP were strongly associated at admission (r = 0.34, p <0.001). In patients with increasing proANP during STEMI, adiponectin also increased (0.5 +/- 0.3 vs 0.1 +/- 0.1 mg/L, p = 0.026). During follow-up, patients with higher adiponectin at admission had increased risk of all-cause mortality and MACE (both, p <0.001). After adjustment for confounding risk factors by Cox regression analysis, adiponectin remained an independent predictor of all-cause mortality and MACE: hazard ratio 1.31 (95% confidence interval 1.07 to 1.60; p = 0.009) and 1.31 (95% confidence interval 1.09 to 1.57; p = 0.004), respectively, for each SD increase. However, the association vanished when proANP was included in the analysis. In conclusion, adiponectin is associated with an increased risk of all-cause mortality and MACE. However, concomitantly elevated proANP levels appear to confound the association between adiponectin and worsened outcome. PMID- 26361830 TI - Evaluation of biodegradable polymer conduits--poly(L-lactic acid)--for guiding sciatic nerve regeneration in mice. AB - Polymeric biomaterials are often used for stimulating nerve regeneration. Among different conduits, poly(lactide acid) - PLA polymer is considered to be a good substrate due to its biocompatibility and resorbable characteristics. This polymer is an aliphatic polyester which has been mostly used in biomedical application. It is an organic compound with low allergenic potential, low toxicity, high biocompatibility and predictable kinetics of degradation. In this study we fabricated and evaluated a PLA microporous hollow fiber as a conduit for its ability to bridge a nerve gap in a mouse sciatic nerve injury model. The PLA conduit was prepared from a polymer solution, throughout extrusion technique. The left sciatic nerve of C57BL/6 mouse was transected and the nerve stumps were placed into a resorbable PLA (PLA group) or a PCL conduit (PCL group), n=5 each group. We have also used another group in which the nerves were repaired by autograft (autograft group, n=5). Motor function was analyzed according to sciatic functional index (SFI). After 56days, the regenerated nerves were processed for light and electron microscopy and morphometric analyses were performed. A quantitative analysis of regenerated nerves showed significant increase in the number of myelinated fibers and blood vessels in animals that received PLA conduit. The PLA group exhibited better overall tissue organization compared to other groups. Presenting well-organized bundles, many regenerating clusters composed of preserved nerve fibers surrounded by layers of compacted perineurium-like cells. Also the SFI revealed a significant improvement in functional recovery. This work suggests that PLA conduits are suitable substrate for cell survival and it provides an effective strategy to be used to support axonal growth becoming a potential alternative to autograft. PMID- 26361831 TI - Reply: Splenic preservation during open and minimally invasive distal pancreatectomy in benign disease. PMID- 26361832 TI - Social media and surgery: An alternative view. PMID- 26361833 TI - Hand-assisted laparoscopic surgery (HALS) is associated with less-restrictive ventilatory impairment and less risk for pulmonary complication than open laparotomy in thoracoscopic esophagectomy. AB - BACKGROUND: Esophagectomy with extended lymphadenectomy improves prognosis but it is associated with high morbidity and mortality. The thoracoscopic approach is associated with fewer pulmonary complications. Abdominal wall injury greatly affects pulmonary function and complication rates during the acute postoperative phase. In this study we aimed to compare the incidence of pulmonary complications and respiratory recovery after thoracoscopic esophagectomy in the prone position with hand-assisted laparoscopic surgery (HALS) versus open laparotomy (OL). METHODS: This was a case-matched control study of patients with esophageal cancer who underwent thoracoscopic esophagectomy in the prone position. Thirty-two patients in the HALS group and 32 patients in the OL group were selected by the use of propensity score matching. Operative outcomes and perioperative changes in respiratory function were compared. RESULTS: There was no operative mortality in either group. Estimated blood loss was less in the HALS group (P < .001). The incidence of postoperative pneumonia was 6.2% (4/64) overall; it was less in the HALS group (0%) than in the OL group (12.5%) (P = .016). There were no differences in preoperative vital capacity (VC) and percent predicted vital capacity (%VC). Each parameter, including the ratio of the postoperative to preoperative %VC (%VC ratio), reached its nadir on postoperative day 7 in both groups but was greater in the HALS group (VC, 2.91 +/- 0.68 L vs 2.53 +/- 0.53 L, P = .018; %VC, 90.62 +/- 16.92% vs 78.91 +/- 16.65%, P = .007; %VC ratio, 80.90 +/- 9.87% vs 72.09 +/- 11.95%, P = .002). At 1 and 3 months, respiratory recovery was seen in both groups but more so in the HALS group. At 6 months, further respiratory recovery was seen in both groups, without any significant intergroup differences. CONCLUSION: During the acute phase after thoracoscopic esophagectomy in the prone position, HALS is associated with less-restrictive ventilatory impairment, fewer subsequent pulmonary complications, and less blood loss than OL. The combination of HALS and thoracoscopic esophagectomy in the prone position is less invasive on respiratory function. PMID- 26361834 TI - Analysis of an institutional protocol for thyroid lobectomy: Utility of routine intraoperative frozen section and expedited (overnight) pathology. AB - BACKGROUND: Intraoperative frozen section (FS) often is performed in patients who undergo thyroid lobectomy to determine the need for completion thyroidectomy. At our institution, if FS pathology is benign, final pathology is expedited overnight. The aim of this study was to determine the utility of FS and to identify a cost-effective management algorithm for thyroid lobectomy. METHODS: A retrospective review was performed of patients who underwent thyroid lobectomy between January 2009 and May 2013. Preoperative cytology ranged from "benign" to "suspicious for malignancy." Clinically significant cancers were defined as >1 cm in size, or multifocal microcarcinomas. RESULTS: Of the 192 patients who underwent thyroid lobectomy with FS, FS was suspicious for malignancy in 5 (3%) patients; 1 (0.5%) underwent immediate completion thyroidectomy. On final pathology, 9 (5%) patients had clinically significant cancers and underwent completion thyroidectomy. FS had a sensitivity and positive predictive value of 22% and 40%, respectively, in identifying clinically significant thyroid cancer. Cost of thyroid lobectomy at varying rates of same-day discharge favored thyroid lobectomy without FS but with expedited pathology for all scenarios. CONCLUSION: At our institution, there appears to be limited utility of FS at the time of thyroid lobectomy given the low predictive value for diagnosing a clinically significant thyroid cancer. In patients who are admitted overnight, expedited pathology is slightly less costly and may improve patient quality-of-life and decrease costs by avoiding delayed completion thyroidectomy. Overnight pathology for patients who undergo thyroid lobectomy may achieve modest cost-savings depending on institutional FS results and rates of malignancy. PMID- 26361835 TI - Verification of nuclear data for the Tsukuba plan, a newly developed treatment planning system for boron neutron capture therapy. AB - Various verifications were performed to apply JENDL-4.0 as nuclear data for a newly developed treatment planning system with a homogeneous or precise human like phantom. The nitrogen dose calculated by JENDL-4.0 differed slightly from that calculated by ENDF/B-VII.0. However, the total weighted dose-based dose volume histogram in the boron neutron capture therapy (BNCT) treatment for brain tumors calculated by JENDL-4.0 was in good agreement with the results of the ENDF/B-VII.0 calculation. Therefore, calculation with JENDL-4.0 can be applied to the BNCT dose calculation. PMID- 26361836 TI - Hepatitis B virus infection among institutionalized mentally ill patients in Brazil. AB - OBJECTIVES: The main objective was to evaluate HBV infection and occult HBV infection (OBI) cases in mentally ill patients based on serological and molecular profiles. MATERIAL AND METHODS: Serum samples of 333 long-stay mentally ill patients were tested for the prevalence of HBV markers by serological (ELISA) and molecular (PCR) assays. The PCR products were sequenced to determine viral genotypes. RESULTS: It was observed a global prevalence of 12.9% (43/333) for HBV infection markers, considering HBsAg and/or anti-HBc positivity. Fourteen samples tested positive for anti-HBs alone. All samples positive (n=57) for any HBV serological markers were tested for HBV-DNA and six were positive: HBsAg/anti-HBc (n=1), anti-HBc/anti-HBs (n=1), anti-HBs alone (n=1), and anti-HBc alone (n=3). The rate of OBI was 9.2% (5/54) from samples that were anti-HBc and/or anti-HBs positive. All sequenced samples were characterized as genotype A. CONCLUSION: The high rate of HBV infections found in this study suggests the possibility of HBV transmission due to risk factors displayed by some patients, and highlights the importance of vaccination of susceptible patients and the staff of that institution. PMID- 26361837 TI - High prevalence and incidence of HIV-1 in a counseling and testing center in the city of Itajai, Brazil. AB - Itajai is a port city in southern Brazil with one of the highest incidence and mortality rates from AIDS in the country. The prevalence and incidence of HIV infection were investigated in 1085 of 3196 new HIV-1 infection cases evaluated in the counseling and testing center of Itajai from January 2002 to August 2008. Recent infections were assessed using the BEDTM, and pol region sequencing was performed in 76 samples. The prevalence ranged from 3.08% to 6.17% among women and from 10.26% to 17.36% among men. A total of 17% of infections were classified as recent, with annual incidence varying from 1.6% to 4.8 per 100 patient/year among women and from 2.05% to 8.5 per 100 patient/year among men. Pol sequences were obtained from 38 randomly recent infections selected individuals: 71% were infected by subtype C, 24% B, 2% D, and 2% F1. Among 38 subjects with established infection, 76% were subtype C, and 24% B. Transmitted drug resistance was detected in 18.4% of recent infection subjects (7.8% to nucleoside analog reverse transcriptase inhibitors, 5.2% to non-nucleoside reverse-transcriptase inhibitors, and 5.2% protease inhibitors) and 5.2% of subjects with established infection had nucleoside analog reverse-transcriptase inhibitors resistance. The high prevalence and incidence of HIV infection in this region is unprecedented in studies involving cases evaluated in the counseling and testing centers in Brazil. PMID- 26361838 TI - Sentinel site surveillance of nontuberculous mycobacteria pulmonary diseases in Zhejiang, China, 2011-2013. PMID- 26361839 TI - Visceral Leishmaniasis/HIV co-infection in northeast Brazil: evaluation of outcome. AB - Since the beginning of the HIV burden, Visceral Leishmaniasis (VL)/HIV co infection has been diagnosed not only in areas where VL is endemic (Latin America, India, Asia, Southern Europe), but also in North America, were it is considered an opportunistic disease. Clinical presentation, diagnostic tests sensitivity and treatment response in this population differs from VL alone. OBJECTIVES: To evaluate factors related to an unfavorable outcome in patients with VL/HIV diagnosis in a reference center in northeast Brazil. METHODS: Co infected patients, diagnosed from 2010 to 2012, were included. Data from medical records were collected until one year after VL treatment completion. RESULTS: Forty-two HIV-infected patients were included in the study. Anemia, leukopenia, and thrombocytopenia were present in 95%, 70.7%, and 63.4%, respectively. Mean T CD4+ (LTCD4) lymphocyte count was 183 cells/dL. Highly active antiretroviral therapy (HAART) was being used by 54.7% of cases. A favorable outcome was seen in 71.4% of cases. Recurrence of VL occurred in nine patients and deaths were secondary to infectious complications (3/42 patients). Very low LTCD4 count (<100 cells/dL) was the only independent variable associated with an unfavorable outcome in multivariate analysis (p=0.03). CONCLUSION: Low LTCD4 count at presentation was associated with unfavorable outcome in VL/HIV patients. PMID- 26361840 TI - Assessment of health-related quality of life and related factors in patients with chronic liver disease. AB - BACKGROUND AND OBJECTIVES: Assessing health-related quality of life is an important aspect of clinical practice. Thus, the present study attempts to assess the health-related quality of life of patients with chronic liver disease. METHODS: A cross-sectional survey was conducted on 133 chronic liver disease patients, using three instruments: a demographic questionnaire, the Chronic Liver Disease Questionnaire, and Model for End-Stage Liver Disease index. Variables were expressed as frequencies, percentages, means, and standard deviations. The statistical analysis included Pearson's correlation, Student's t-test, and analysis of variance (p<0.05 was considered significant). RESULTS: The mean age of included subjects was 50.5+/-13.3 years. The majority were male (66.2%), Caucasian (70.7%), and had a family income of US$329-US$658.2. Over half of the patients (56.4%) were infected by hepatitis C virus and 93.2% had low Model for End-Stage Liver Disease scores. Model for End-Stage Liver Disease score was related to age (r=0.185; p=0.033). Higher mean Chronic Liver Disease Questionnaire scores were obtained for emotional function (39.70/SD+/-12.98) and while lower scores were obtained for abdominal symptoms (16.00/SD+/-6.25). Fifty two patients (39.1%) presented overall low (<5) Chronic Liver Disease Questionnaire scores. Furthermore, Chronic Liver Disease Questionnaire score was related to family income (r=0.187, p=0.031). CONCLUSION: Most individuals presented high mean Chronic Liver Disease Questionnaire scores, indicating low health-related quality of life, especially individuals with low family income. PMID- 26361841 TI - Worrisome trends in rising minimum inhibitory concentration values of antibiotics against methicillin resistant Staphylococcus aureus - Insights from a tertiary care center, South India. AB - INTRODUCTION: Appearance of isolated reports of resistance to anti-methicillin resistant Staphylococcus aureus (MRSA) drugs is worrisome underscoring the need to continuously monitor the susceptibility of clinical MRSA isolates to these drugs. Hence, the present study is conducted to determine the susceptibility of MRSA isolates to various classes of anti-MRSA drugs such as vancomycin (glycopeptide), daptomycin (lipopeptide), tigecycline (glycylcycline), and linezolid (oxazolidinone) to determine the MIC50 and MIC90 values, and to observe MIC creep over a three year period, if any, with respect to these drugs. METHODS: A total of 200 isolates of MRSA obtained from clinical specimens were included. MIC was determined by E-test for anti-MRSA antibiotics vancomycin, linezolid, daptomycin, and tigecycline. Non-parametric methods (Kruskal-Wallis and Chi square test) were used to assess MIC trends over time. In addition, MIC50 and MIC90 values were also calculated. RESULTS: No isolate was found resistant to vancomycin, daptomycin, or linezolid; five isolates were resistant to tigecycline. Seven VISA isolates were encountered with the MIC value for vancomycin of 4MUg/mL. MIC values for vancomycin, tigecycline, linezolid showed a definite increase over a 3-year period which was statistically significant with p values <0.0001, 0.0032, 0.0242, respectively. When the percentage of isolates with a median MIC value less than or equal to that of the index year was calculated, the change was most striking with vancomycin. The proportion of isolates with higher MIC values was greater in 2014 than 2012 and 2013. CONCLUSION: MIC creep was notably observed with vancomycin, and to some extent with tigecycline and linezolid. Selection pressure may result in creeping MICs, which may herald the emergence of resistant organisms. PMID- 26361843 TI - Molecular characterization of microbial contaminants isolated from Umbilical Cord Blood Units for transplant. AB - Disposal of Umbilical Cord Blood Units due to microbial contamination is a major problem in Cord Blood Banks worldwide as it reduces the number of units available for transplantation. Additionally, economic losses are generated as result of resources and infrastructure used to obtain such units. Umbilical Cord Blood Units that showed initial microbial contamination were subject to strains isolation, identification, and characterization by sequencing the 16S rRNA gene and Enterobacterial Repetitive Intergenic Consensus (ERIC-PCR). Moreover, tests of antimicrobial resistance/sensitivity and phenotypic activities that may play an important role in microbial infection were performed. Microbial contamination was detected in 120 Umbilical Cord Blood Units (2.31%) in the period from 2003 to 2013. The most frequently isolated strains were Enterococcus faecium, followed by Staphylococcus epidermidis, Escherichia coli, Enterococcus faecalis, Staphylococcus haemoliticus, Klebsiella pneumoniae, Enterococcus durans, Lactobacillus helveticus, Enterococcus hiriae and Roseomonas genomospecies 5. The ERIC-PCR assays revealed a wide genetic diversity in some strains although belonging to the same genus and specie, indicating different sources of contamination. Broad-spectrum penicillins, third generation cephalosporins, aminoglycosides, and fluoroquinolones showed lower inhibitory activity on the tested strains. All strains were proteolytic, 67.69% were amylase-positive, 27.6% hemolysis-positive, and 34.71% nuclease-positive. The most common sources of contamination were: vaginal flora, digestive tract, and skin flora, highlighting the need for staff training in good manufacturing practices in collection SCU since all contaminants identified are part of the microbial flora of the donors. Implications and consequences in the therapeutic use of Umbilical Cord Blood Units for transplantation contaminated by multiresistant bacteria in immunocompromised patients are discussed. PMID- 26361842 TI - Cryptococcus laurentii fungaemia in a cervical cancer patient. AB - Infections caused by emerging Cryptococcus non-neoformans species are being reported with increasingly frequency. Here, we present a case of fungaemia by Cryptococcus laurentii in a woman receiving aggressive immunosuppressive therapy for cervical neoplasia. Three venous blood samples were aseptically collected on consecutive days and C. laurentii was isolated and identified through phenotypic and molecular methods. After central venous catheter removal and appropriate antifungal therapy, the patient showed significant improvement and blood culture became negative. Thus, patients following immunosuppressive therapies and using invasive medical devices are at risk of C. laurentii blood infections. PMID- 26361844 TI - Molecular cloning, expression pattern, and chemical analysis of heat shock protein 70 (HSP70) in the mudskipper Boleophthalmus pectinirostris: Evidence for its role in regulating spermatogenesis. AB - Heat shock protein 70 (HSP70) is molecular chaperone that is important for reproductive biological processes. In this study, a full length HSP70 from the mudskipper (Boleophthalmus pectinirostris) was characterized. It was found to contain: a 108 bp 5'-untranslated region, a 208 bp 3'-untranslated region, and a 1953 bp open reading frame, which encodes a protein of 650 amino acids with a theoretical molecular weight of 71.1 kDa and an isoelectric point of 5.17. RT-PCR analysis revealed that HSP70 was ubiquitously expressed in all major tissues with differential expression levels. This suggests that HSP70 has vital and conserved biological functions. HSP70 was localized mainly in the cytoplasm of germinal cells, indicating an important role of this protein during spermatogenesis. In response to heat stress, the testes presented abnormal morphology in connective tissues, in which HSP70 immunoreactivity was not observed. HSP70 mRNA expression in the gill, liver, and testes was significantly increased, which suggests that HSP70 plays an important role in protection against heat stress. PMID- 26361846 TI - Analysis of UB and L40 resistance related to deltamethrin in Drosophila kc cells. AB - Pests have been subjected to heavy selection pressure, and the development of resistance to pyrethroid has been recorded. It is extremely valuable to identify the resistance genes that are relevant for pest control. In our previous studies, we reported that UBL40 is the deltamethrin resistance-associated gene. UBL40 is cleaved by specific endopeptidases to release UB and L40. Whether UB or L40 participates in deltamethrin resistance requires further study. In this study, quantitative real-time PCR was applied to reveal that UB and L40 were both overexpressed in Drosophila kc cells after deltamethrin stimulation. To investigate the roles of UB and L40 further, RNA interferences (RNAi) and cell transfections were utilized. UB and L40 knockdown both significantly reduced the level of resistance of RNAi-treated cells after 48 h, and the overexpressions of UB and L40 in Drosophila kc cells conferred a degree of protection against deltamethrin. These results represent the first evidence that UB and L40 both play roles in the regulation of deltamethrin resistance and that this study could help us to elucidate the resistance mechanisms and identify new target genes associated with resistance. PMID- 26361845 TI - Identification of transcription factors and gene clusters in rabbit smooth muscle cells during high flow-induced vascular remodeling via microarray. AB - Sustained blood flow, especially high blood flow causes the remodeling of arteries. The molecular mechanism of vascular remodeling has been mainly investigated in cultured cells. However, the in vivo molecular mechanism is poorly understood. In this study, we performed microarray analysis to explore the gene expression profile of smooth muscle cells (SMCs) during vascular remodeling. Transcriptional profiles indicated that 947 genes were differentially expressed in SMCs responding to high flow compared with the sham control, of which 617 genes were up-regulated and 330 genes were down-regulated. Gene ontology analysis revealed the special participation of extracellular matrix related genes during high flow-induced vascular remodeling. KEGG pathway analysis showed the enrichment of metabolism and immune function associated genes in SMCs exposed to high flow. Besides, we also identified 25 differentially expressed transcription factors potentially impacted by hemodynamic insult. Finally, we revealed FOXN4 as a novel transcription factor that could modulate MMP2 and MMP9 transcriptional activity. Collectively, our results revealed major gene clusters and transcription factors in SMCs during vascular remodeling which may provide an insight into the molecular mechanism of vascular remodeling and facilitate the screening of candidate genes for vascular diseases. PMID- 26361847 TI - Evolution of the Sox gene family within the chordate phylum. AB - The ancient Sox gene family is a group of related transcription factors that perform a number of essential functions during embryonic development. During evolution, this family has undergone considerable expansion, particularly within the vertebrate lineage. In vertebrates SOX proteins are required for the specification, development and/or morphogenesis of most vertebrate innovations. Tunicates and lancelets are evolutionarily positioned as the closest invertebrate relatives to the vertebrate group. By identifying their Sox gene complement we can begin to reconstruct the gene set of the last common chordate ancestor before the split into invertebrates and vertebrate groups. We have identified core SOX family members from the genomes of six invertebrate chordates. Using phylogenetic analysis we determined their evolutionary relationships. We propose that the last common ancestor of chordates had at least seven Sox genes, including the core suite of SoxB, C, D, E and F as well as SoxH. PMID- 26361848 TI - The cardiac sodium channel gene SCN5A and its gene product NaV1.5: Role in physiology and pathophysiology. AB - The gene SCN5A encodes the main cardiac sodium channel NaV1.5. This channel predominates the cardiac sodium current, INa, which underlies the fast upstroke of the cardiac action potential. As such, it plays a crucial role in cardiac electrophysiology. Over the last 60years a tremendous amount of knowledge regarding its function at the electrophysiological and molecular level has been acquired. Furthermore, genetic studies have shown that mutations in SCN5A are associated with multiple cardiac diseases (e.g. Brugada syndrome, Long QT syndrome, conduction disease and cardiomyopathy), while genetic variation in the general population has been associated with differences in cardiac conduction and risk of arrhythmia through genome wide association studies. In this review we aim to give an overview of the current knowledge (and the gaps therein) on SCN5A and NaV1.5. PMID- 26361849 TI - Editorial commentary on "Refractory absence seizures: An Italian multicenter retrospective study" by E. Franzoni et al. PMID- 26361850 TI - A translocation t(6;14) in two cases of leiomyosarcoma: Molecular cytogenetic and array-based comparative genomic hybridization characterization. AB - Leiomyosarcomas are malignant mesenchymal tumors that recapitulate smooth muscle cell differentiation. Tumors are characterized by a genetic heterogeneity with complex karyotypes without a tumor-specific genetic aberration. Their pathobiology is still poorly understood and no specific targeted treatment is currently available for these aggressive tumors. For six leiomyosarcomas, cells were cultured and analyzed by combined binary ratio labeling fluorescence in situ hybridization (COBRA-FISH) karyotyping. A t(6;14) was identified in two cases. FISH breakpoint mapping of case L1339 reveals a breakpoint at chromosome 6p21.31 close to HMGA1, and a small deletion was observed on the distal side of the gene. A small homozygous deletion was also found in the breakpoint region of chromosome 14q24.1 involving ACTN1. The second case revealed a der(6)t(6;14)(p21.1;q21.3), with a duplication adjacent to the breakpoint at chromosome 6. Confirmatory FISH revealed a second leiomyosarcoma with an aberration at 14q24.1. Alterations at this locus were found in 5% (2 of 39) of the leiomyosarcomas in this study. The other identified breakpoints appeared to be non-recurrent, because they were not detected in other leiomyosarcomas, uterine leiomyomas, undifferentiated spindle cell sarcomas, or undifferentiated pleomorphic sarcomas. PMID- 26361851 TI - Endurance Exercise-Induced Cardiac Remodeling: Not All Sports Are Created Equal. AB - BACKGROUND: The term endurance sport (ES) is broadly used to characterize any exercise that requires maintenance of high cardiac output over extended time. However, the relative amount of isotonic (volume) versus isometric (pressure) cardiac stress varies across ES disciplines. To what degree ES-mediated cardiac remodeling varies, as a function of superimposed isometric stress, is uncertain. The aim of this study was to compare the cardiac remodeling characteristics associated with two common yet physiologically distinct forms of ES. METHODS: Healthy competitive male long-distance runners (high isotonic, low isometric stress; n = 40) and rowers (high isotonic, high isometric stress; n = 40) were comparatively studied after 3 months of sport-specific exercise training with conventional and speckle-tracking two-dimensional echocardiography. RESULTS: Rowers demonstrated dilated left ventricular (LV) volumes and elevated LV mass (i.e., eccentric LV hypertrophy), whereas runners demonstrated normal LV mass (runners, 88 +/- 11 g/m(2); rowers, 108 +/- 13 g/m(2); P < .001) despite comparatively larger LV volumes (runners, 101 +/- 10 mL/m(2); rowers, 89 +/- 13 mL/m(2); P < .001) consistent with eccentric LV remodeling. Increasing LV mass was associated with increased reliance on early diastolic filling (LV mass vs E'/A' ratio, R = 0.47, P < .001) indicating "mass-dependent" diastolic function. Right ventricular dilation of similar magnitude and LV systolic function, as assessed by numerous complementary indices, were similar in both groups. CONCLUSIONS: Cardiac adaptations differ significantly as a function of ES discipline. Further work is required to determine the mechanisms for this differential adaptation, to develop definitive ES discipline-specific normative values, and to evaluate the optimal therapeutic use of specific ES disciplines among patients with common cardiovascular diseases. PMID- 26361852 TI - A novel method of demonstrating the molecular and functional equivalence between in vitro and plant-produced double-stranded RNA. AB - A biotechnology-derived corn variety, MON 87411, containing a suppression cassette that expresses an inverted repeat sequence that matches the sequence of western corn rootworm (WCR; Diabrotica virgifera virgifera) has been developed. The expression of the cassette results in the formation of a double-stranded RNA (dsRNA) transcript containing a 240 bp fragment of the WCR Snf7 gene (DvSnf7) that confers resistance to corn rootworm by suppressing levels of DvSnf7 mRNA in WCR after root feeding. Internationally accepted guidelines for the assessment of genetically modified crop products have been developed to ensure that these plants are as safe for food, feed, and environmental release as their non modified counterparts (Codex, 2009). As part of these assessments MON 87411 must undergo an extensive environmental assessment that requires large quantities of DvSnf7 dsRNA that was produced by in vitro transcription (IVT). To determine if the IVT dsRNA is a suitable surrogate for the MON 87411-produced DvSnf7 dsRNA in regulatory studies, the nucleotide sequence, secondary structure, and functional activity of each were characterized and demonstrated to be comparable. This comprehensive characterization indicates that the IVT DvSnf7 dsRNA is equivalent to the MON 87411-produced DvSnf7 dsRNA and it is a suitable surrogate for regulatory studies. PMID- 26361853 TI - Proof of concept for a banding scheme to support risk assessments related to multi-product biologics manufacturing. AB - A banding scheme theory has been proposed to assess the potency/toxicity of biologics and assist with decisions regarding the introduction of new biologic products into existing manufacturing facilities. The current work was conducted to provide a practical example of how this scheme could be applied. Information was identified for representatives from the following four proposed bands: Band A (lethal toxins); Band B (toxins and apoptosis signals); Band C (cytokines and growth factors); and Band D (antibodies, antibody fragments, scaffold molecules, and insulins). The potency/toxicity of the representative substances was confirmed as follows: Band A, low nanogram quantities exert lethal effects; Band B, repeated administration of microgram quantities is tolerated in humans; Band C, endogenous substances and recombinant versions administered to patients in low (interferons), intermediate (growth factors), and high (interleukins) microgram doses, often on a chronic basis; and Band D, endogenous substances present or produced in the body in milligram quantities per day (insulin, collagen) or protein therapeutics administered in milligram quantities per dose (mAbs). This work confirms that substances in Bands A, B, C, and D represent very high, high, medium, and low concern with regard to risk of cross-contamination in manufacturing facilities, thus supporting the proposed banding scheme. PMID- 26361854 TI - Hexavalent and trivalent chromium in leather: What should be done? AB - Trivalent chromium compounds are used for leather tanning, and chromium may be released during use of leather goods. In certain instances, small amounts of hexavalent chromium can be formed and released. Both trivalent and hexavalent chromium can elicit allergic skin reaction in chromium sensitised subjects, the latter being significantly more potent. Induction of sensitisation only occurs after exposure to hexavalent chromium. A minority of subjects are sensitised to chromium, and in a fraction of these subjects allergic skin reaction have been described after wearing leather shoes or, less frequently, other leather goods. The evidence that in all these cases the reaction is related to hexavalent chromium is not always strong. The content of hexavalent chromium in leather is regulated in European Union, but rate of release rather than content is relevant for allergic skin reaction. The role of trivalent chromium appear much less relevant if at all. Modern tanning procedure do not pose significant risk due to either hexavalent or trivalent chromium. Dismissing bad quality and worn-off leather goods is relevant in reducing or eliminating the skin reaction. It should also be pointed out that shoe components or substances other than chromium in leather may cause allergic/irritative skin reactions. PMID- 26361855 TI - Roles of ROS mediated oxidative stress and DNA damage in 3-methyl-2-quinoxalin benzenevinylketo-1, 4-dioxide-induced immunotoxicity of Sprague-Dawley rats. AB - 3-methyl-2-quinoxalin benzenevinylketo-1, 4-dioxide (Quinocetone, QCT) has been broadly used to treat dysentery and promote animal growth in food producing animals. However, its potential toxicity could not been neglected as parts of safety assessment according to the acceptable guidelines for QCT administration. In this study, the immunotoxicity of QCT was investigated in male Sprague-Dawley (SD) rats following a 28-day oral exposure at doses of 0, 50, 800, and 2400 mg/kg/day. The food consumption, body weight gain and relative spleen weight were significantly decreased by QCT in a dose-dependent manner. Treatment of rats with QCT also notably suppressed the T-cell proliferation and natural killer (NK) cell activity, accompanied by intracellular reactive oxygen species (ROS) accumulation, antioxidant system inhibition and DNA damage enhancement. Thus, the primary finding of this study is that QCT exposure (2400 mg/kg/day) could cause immunotoxicity in SD rats due to ROS mediated oxidative stress and DNA damage. PMID- 26361856 TI - Effect of exposure routes on the relationships of lethal toxicity to rats from oral, intravenous, intraperitoneal and intramuscular routes. AB - The lethal toxicity values (log 1/LD(50)) of 527 aliphatic and aromatic compounds in oral, intravenous, intramuscular and intraperitoneal routes were used to investigate the relationships of log 1/LD(50) from different exposure routes. Regression analysis shows that the log 1/LD(50) values are well correlated between intravenous and intraperitoneal or intramuscular injections. However, the correlations between oral and intravenous or intraperitoneal routes are relatively poor. Comparison of the average residuals indicates that intravenous injection is the most sensitive exposure route and oral administration is the least sensitive exposure route. This is attributed to the difference in kinetic process of toxicity testing. The toxic effect of a chemical can be similar or significantly different between exposure routes, depending on the absorption rates of chemicals into blood. Inclusion of hydrophobic parameter and fractions of ionic forms can improve the correlations between intravenous and intraperitoneal or oral routes, but not between intraperitoneal and oral routes. This is due to the differences of absorption rate in different exposure environments from different routes. Several factors, such as experimental uncertainty, metabolism and toxic kinetics, can affect the correlations between intravenous and intraperitoneal or oral routes. PMID- 26361857 TI - Feasibility of repeated testing for learning ability in juvenile primates for pediatric safety assessment. AB - Assessment of learning ability in nonhuman primate (NHP) models is sometimes requested by regulatory authorities. The double choice object discrimination task using a Wisconsin General Testing Apparatus (WGTA) approach is typically being applied. In this study, the WGTA approach was performed on 66 juvenile cynomolgus monkeys aged 8-9 months in the predose phase of juvenile toxicity assessment. In addition, reversal learning data of seven control animals/gender were obtained for the weeks 25 and 52 of dosing. Gender differences in the number of days required to pass the habituation, learning or reversal learning phases were statistically comparable, males and females may be combined for statistical analysis. At first instance, the habituation phase was passed on average after 6.4 days, and the learning test on average after 8.6 days with improvement to 2.0 2.6 days for habituation and 6.4-6.7 days for learning in weeks 52. Power analysis (alpha = 0.05, one-sided t-test) revealed a sample size of 8 and 41 to predict a 50% and 20% difference, respectively. In conclusion, examination for learning ability, but not for memory ability (during repeated testing) is feasible in juvenile NHPs using the WGTA approach. PMID- 26361858 TI - RNAi technologies in agricultural biotechnology: The Toxicology Forum 40th Annual Summer Meeting. AB - During the 40th Annual Meeting of The Toxicology Forum, the current and potential future science, regulations, and politics of agricultural biotechnology were presented and discussed. The meeting session described herein focused on the technology of RNA interference (RNAi) in agriculture. The general process by which RNAi works, currently registered RNAi-based plant traits, example RNAi based traits in development, potential use of double stranded RNA (dsRNA) as topically applied pesticide active ingredients, research related to the safety of RNAi, biological barriers to ingested dsRNA, recent regulatory RNAi science reviews, and regulatory considerations related to the use of RNAi in agriculture were discussed. Participants generally agreed that the current regulatory framework is robust and appropriate for evaluating the safety of RNAi employed in agricultural biotechnology and were also supportive of the use of RNAi to develop improved crop traits. However, as with any emerging technology, the potential range of future products, potential future regulatory frameworks, and public acceptance of the technology will continue to evolve. As such, continuing dialogue was encouraged to promote education of consumers and science-based regulations. PMID- 26361859 TI - Systematic review and meta-analysis of the efficacy and hypoglycemic safety of gliclazide versus other insulinotropic agents. AB - AIMS: Sulfonylureas are well positioned in treating type 2 diabetes, after lifestyle modification and metformin. The sulfonylurea gliclazide was given preference over glibenclamide in older people with type 2 diabetes in the World Health Organization model list of essential medicines. Consequently, a systematic review and meta-analysis of randomized controlled trials of the efficacy and safety of gliclazide versus other oral insulinotropic agents (sulfonylureas, dipeptidyl peptidase-4 inhibitors, and glinides) was performed. METHODS: Two reviewers searched MEDLINE for studies of >=12 weeks duration in adults with type 2 diabetes. The key search word was "gliclazide", filtered with "randomized controlled trial", "human" and "19+ years". Differences were explored in mean change in glycated hemoglobin (HbA(1c)) from baseline (primary outcome) and risk of hypoglycemia (secondary outcome) between gliclazide and other oral insulinotropic agents; and other sulfonylureas. RESULTS: Nine out of 181 references reported primary outcomes, of which 7 reported secondary outcomes. Gliclazide lowered HbA1c more than other oral insulinotropic agents, with a weighted mean difference of -0.11% (95%, CI -0.19 to -0.03%, P=0.008, I(2)=60%), though not more than other sulfonylureas (-0.12%; 95%, CI -0.25 to 0.01%, P=0.07, I(2)=77%). Risk of hypoglycemia with gliclazide was not different to other insulinotropic agents (RR 0.85; 95%, CI 0.66 to 1.09, P=0.20, I(2)=61%) but significantly lower than other sulfonylureas (RR 0.47; 95%, CI 0.27 to 0.79, P=0.004, I(2)=0%). CONCLUSION: Compared with other oral insulinotropic agents, gliclazide significantly reduced HbA1c with no difference regarding hypoglycemia risk. Compared with other sulfonylureas, HbA1c reduction with gliclazide was not significantly different, but hypoglycemia risk was significantly lower. PMID- 26361860 TI - Prevalence of resistant hypertension and associated factors in Japanese subjects with type 2 diabetes. AB - OBJECTIVE: The prevalence of treatment resistant hypertension (RH) depends on methods used for blood pressure (BP) measurements, goals of BP, and therapeutic efforts in terms of medication and adherence. We focused on diabetic subjects and explored the prevalence of RH in primary care practice. METHODS: In 1737 subjects with type 2 diabetes who continued regular visits, office BP was evaluated by multiple measurements over one year. RH was defined as using more than four antihypertensive drugs or failure to achieve the goal with three antihypertensive drugs from different classes. The RH prevalence was investigated with BP goals <130/80 and 140/90 mmHg. RESULTS: The percentage of subjects who achieved BP goals <130/80 and 140/90 were 70.5% and 93.8% with adherence to medication >=95%, and the corresponding prevalence rates of RH in treated subjects were 28.4% and 21.8%, respectively. Factors independently associated with RH were age (odds ratio 1.02 [95% CI 1.01-1.04]), body mass index (1.10 [1.06-1.13]), variability in systolic BP (1.06 [1.02-1.09]), triglycerides (2.86 [1.34-6.11]), macroalbuminuria (3.33 [2.03-5.48]), estimated glomerular filtration rate (0.98 [0.97-0.99]), retinopathy (1.91 [1.39-2.61]), and family history of hypertension (1.85 [1.23-2.21]). Worsening albuminuria and glomerular filtration rate enhanced the prevalence of RH in a graded manner. CONCLUSION: Careful estimation of office BP values over one year with a high achievement of BP goals and adequate adherence revealed that the prevalence of RH in type 2 diabetes is high. RH was characterized by accumulation of cardiovascular genetic and environmental risks. PMID- 26361861 TI - Current status of hepatocyte xenotransplantation. AB - The treatment of acute liver failure, a condition with high mortality, comprises optimal clinical care, and in severe cases liver transplantation. However, there are limitations in availability of organ donors. Hepatocyte transplantation is a promising alternative that could fill the medical need, in particular as the bridge to liver transplantation. Encapsulated porcine hepatocytes represent an unlimited source that could function as a bioreactor requiring minimal immunosuppression. Besides patients with acute liver failure, patients with alcoholic hepatitis who are unresponsive to a short course of corticosteroids are a target for hepatocyte transplantation. In this review we present an overview of the innate immune barriers in hepatocyte xenotransplantation, including the role of complement and natural antibodies; the role of phagocytic cells and ligands like CD47 in the regulation of phagocytic cells; and the role of Natural Killer cells. We present also some illustrations of physiological species incompatibilities in hepatocyte xenotransplantation, such as incompatibilities in the coagulation system. An overview of the methodology for cell microencapsulation is presented, followed by proof-of-concept studies in rodent and nonhuman primate models of fulminant liver failure: these studies document the efficacy of microencapsulated porcine hepatocytes which warrants progress towards clinical application. Lastly, we present an outline of a provisional clinical trial, that upon completion of preclinical work could start within the upcoming 2-3 years. PMID- 26361862 TI - Impacts of low peritoneal cancer index on the survival outcomes of patient with peritoneal carcinomatosis of colorectal origin. AB - INTRODUCTION: The combination of cytoreductive surgery (CRS) and perioperative chemotherapy (PIC) have been proposed as an innovative technique for peritoneal carcinomatosis and is currently considered as a standard treatment for colorectal peritoneal carcinomatosis (CRPC) in selected patients. Peritoneal cancer index (PCI) has been suggested to be the most important prognostic factors for the outcomes of patients with CRPC. In this paper, we have studied patients with CRPC and a very low PCI of 5 or less and their survival outcomes. METHODS: This is a retrospective study of prospectively collected data of 60 consecutive patients with CRPC and PCI <= 5, who underwent CRS and PIC by the same surgical team at St George hospital in Sydney, Australia between January 1996 and April 2015. Clinical outcomes of these patients were analysed. RESULTS: Hospital mortality was 0%. 14 patients (23.4%) had grade III/IV morbidity. The median follow-up was 22.2 months (range = 0.1-104.2). The median survival was 80.6 months (95% confidence interval (CI) = 35.1-126.1), with an overall 1-year, 3-year, and 5 year survival rate of 96.1%, 72.6% and 54.7% respectively. Among 60 patients, 31 patients experienced the recurrence of the disease (51.7%). The median disease free survival was 10.8 months (95% CI = 7.2-14.4). CONCLUSION: This innovative approach combining CRS and PIC has shown encouraging outcomes and offers hope for patients with CRPC. Our results suggest that CRS and PIC can be performed safely to provide significant survival benefits for patients with low volume of disease. Early referral to specialist centre for evaluation is warranted for better survival outcomes. PMID- 26361863 TI - Current knowledge on evidence-based shockwave treatments for shoulder pathology. AB - Shoulder pain is one of the most common musculoskeletal pathologies. Treatment by ESWT (extracorporeal shockwave therapy) has emerged as an alternative when conservative treatment fails in rotator cuff calcific tendinopathy, prior to invasive procedures. The clinical efficacy of ESWT in non-calcific tendinopathy remains controversial. The good results in the treatment of rotator cuff calcifications, have led to indications of ESWT being expanded to other shoulder pathologies. We review the current state of indications and evidence based practice. PMID- 26361864 TI - Immunogenicity of Semliki Forest virus based self-amplifying RNA expressing Indian HIV-1C genes in mice. AB - Development of recombinant vaccines is considered as a promising approach to prevent transmission and eradication of HIV/AIDS. Candidate vaccines tested so far have shown poor to modest efficacy. Self-amplifying RNAs of positive strand alphaviruses are reported to be promising vectors for development of recombinant vaccines. This study describes the construction, in vitro expression and in vivo immunogenicity of recombinant RNA vaccines developed by individually cloning gag, env and polRT genes of primary HIV-1C Indian isolates using Semliki Forest virus (SFV) vector. HIV-1C specific T cell responses were detected in mice immunized with rSFV2gen/gag RNA by IFN-gamma ELISPOT assay. Furthermore, using flow cytometry based intracellular cytokine staining (ICCS) assay HIV-1C specific IL-2 responses were detected in immunized mice that were mediated by both CD4(+) and CD8(+) T cells. Mice immunized with rSFV2gen/env RNA elicited HIV-1C Env-specific antibodies as detected by gp120 ELISA. The Env, Gag and Pol (RT) RNA constructs in combination elicited better HIV-1C Env-specific humoral responses compared to mice immunized with Env RNA alone. In conclusion, rSFV2gen RNA constructs encoding HIV-1C antigens elicited clear cell mediated and humoral immune responses in mice, thus demonstrating the potential of self-amplifying rSFV2gen RNA as a promising candidate for anti-HIV vaccine development. PMID- 26361866 TI - Starch structure in developing barley endosperm. AB - Barley spikes of the cultivars/breeding lines Gustav, Karmose and SLU 7 were harvested at 9, 12 and 24 days after flowering in order to study starch structure in developing barley endosperm. Kernel dry weight, starch content and amylose content increased during development. Structural analysis was performed on whole starch and included the chain-length distribution of the whole starches and their beta-limit dextrins. Karmose, possessing the amo1 mutation, had higher amylose content and a lower proportion of long chains (DP >=38) in the amylopectin component than SLU 7 and Gustav. Structural differences during endosperm development were seen as a decrease in molar proportion of chains of DP 22-37 in whole starch. In beta-limit dextrins, the proportion of Bfp-chains (DP 4-7) increased and the proportion of BSmajor-chains (DP 15-27) decreased during development, suggesting more frequent activity of starch branching enzymes at later stages of maturation, resulting in amylopectin with denser structure. PMID- 26361865 TI - An extracellular laccase with potent dye decolorizing ability from white rot fungus Trametes sp. LAC-01. AB - A novel laccase was purified from fermentation broth of white rot fungus Trametes sp. LAC-01 using an isolation procedure involving three ion-exchange chromatography steps on DEAE-cellulose, SP-Sepharose, and Q-Sepharose, and one gel-filtration step. The purified enzyme (TSL) was proved as a monomeric protein with a Mr of 59kDa based on SDS-PAGE and FPLC. Partial amino acid sequences were obtained by LC-MS/MS sharing considerably high sequence similarity with that of other laccases. It possessed optimal pH of 2.6 and temperature of 60 degrees C using ABTS as the substrate. The Km of the laccase toward ABTS was estimated to 30.28MUM at pH 2.6 and 40 degrees C. TSL manifested considerably high oxidizing activity toward ABTS, but was avoid of degradative activity toward benzidine, caftaric acid, etc. It was effective in the decolorization of phenolic dyes - Bromothymol Blue and Malachite Green with decolorization rate higher than 60% after 24h of incubation. Adjunction of Cu(2+) with the final concentration of 2.0mmol/L significantly activated laccase production with a steady high level of 275.8-282.2U/mL in 96-144h. The high yield and short production period makes Trametes sp. LAC-01 and TSL potentially useful for industrial and environmental application and commercialization. PMID- 26361867 TI - Effect of obesity in electrocardiographic criteria: is that important? PMID- 26361868 TI - Expression of thymosin beta-4 in human periodontal ligament cells and mouse periodontal tissue and its role in osteoblastic/cementoblastic differentiation. AB - A recent report showed that thymosin beta-4 (Tbeta4) is expressed during the development of tooth germ, but its effect on osteoblastic/cementoblastic differentiation is a controversial topic. Furthermore, the precise expression and function of Tbeta4 in periodontal tissue remains unclear. Therefore, the purpose of this study was to investigate the immunolocalization of Tbeta4 in the developing periodontium of mouse, the function of Tbeta4 in osteoblastic/cementoblastic differentiation, and the underlying mechanism regulating periodontal regeneration in human periodontal ligament cells (hPDLCs), cementoblasts, and osteoblasts. Tbeta4 expression was observed in differentiating hPDLCs, osteoblasts of the periodontium during development, as well as in mature tissue. Higher Tbeta4 expression was observed in hPDLCs than in cementoblasts and osteoblasts in the developing periodontium. The expression of Tbeta4 mRNA and protein gradually increased during PDL cell differentiation. The downregulation of Tbeta4 expression by Tbeta4 siRNA transfection inhibited osteoblastic differentiation by decreasing calcium nodule formation, alkaline phosphatase (ALP) activity, and mRNA expression of differentiation markers in hPDLCs, cementoblasts, and osteoblasts. In contrast, Tbeta4 activation using a Tbeta4 peptide, promoted these processes by activation of Akt, p38, ERK MAPKs, and the NF-kappaB pathway. The expression of nuclear NFATc1 was upregulated by Tbeta4 peptide in hPDLCs. Inhibition of the calcineurin/NFATc1 pathway by cyclosporin A and FK506, attenuated Tbeta4-induced osteoblastic differentiation and activation of Wnt-related genes, as well as nuclear beta-catenin in hPDLCs. In conclusion, this study demonstrates, for the first time, that Tbeta4 is expressed in developing periodontal tissue and that its expression is associated with osteoblastic/cementoblastic differentiation. These results suggests that Tbeta4 is a potential therapeutic target for periodontal regeneration or bone disease. PMID- 26361869 TI - Resveratrol and curcumin ameliorate di-(2-ethylhexyl) phthalate induced testicular injury in rats. AB - The present study aimed to evaluate the protective role of resveratrol and curcumin on oxidative testicular damage induced by di-(2-ethylhexyl) phthalate (DEHP). Male Wistar rats were divided into six groups; three groups received oral daily doses of DEHP (2g/kgBW) for 45days to induce testicular injury. Two of these groups received either resveratrol (80mg/kgBW) or curcumin (200mg/kgBW) orally for 30days before and 45days after DEHP administration. A vehicle-treated control group was also included. Another two groups of rats received either resveratrol or curcumin alone. Oxidative damage was observed by decreased levels of total antioxidant capacity (TAC) and glutathione (GSH) and increased malondialdehyde (MDA) level in the testes of DEHP-administered rats. Serum testosterone level as well as testicular marker enzymes activities; acid and alkaline phosphatases (ACP and ALP) and lactate dehydrogenase (LDH) showed severe declines. DEHP administration caused significant increases in the testicular gene expression levels of Nrf2, HO-1, HSP60, HSP70 and HSP90 as well as a significant decrease in c-Kit protein when compared with the control group. Histopathological observations provided evidence for the biochemical and molecular analysis. These DEHP-induced pathological alterations were attenuated by pretreatment with resveratrol and curcumin. We conclude that DEHP-induced injuries in biochemical, molecular and histological structure of testis were recovered by pretreatment with resveratrol and curcumin. The chemoprotective effects of these compounds may be due to their intrinsic antioxidant properties along with boosting Nrf2, HSP 60, HSP 70 and HSP 90 gene expression levels and as such may be useful potential tools in combating DEHP-induced testicular dysfunction. PMID- 26361870 TI - Arginine vasotocin V1a2 receptor and GnRH-I co-localize in preoptic neurons of the sex changing grouper, Epinephelus adscensionis. AB - The arginine vasotocin/vasopressin (AVT/AVP) and gonadotropin releasing hormone (GnRH) systems are known to control sexual behaviors and reproduction, respectively, in different vertebrate groups. However, a direct functional connection between these two neuroendocrine systems has not been demonstrated for any vertebrate species. Therefore, the objective of this research was to test the hypothesis that AVT acts on the GnRH system via an AVT V1a receptor in a sex changing grouper species, the rock hind, Epinephelus adscensionis. AVT V1a2 receptors were co-localized with GnRH-I on neurons in the preoptic anterior hypothalamus identifying a structural linkage between the AVT system and GnRH-I. Transcripts for avt, gnrh-I, and two AVT receptor subtypes (v1a1 and v1a2) were isolated and characterized for E. adscensionis and their expression was measured in males and females by q-RT-PCR. Translation of V1a-type cDNA sequences revealed two distinct forms of the AVT V1a receptor in E. adscensionis brain similar to those reported for other species. The observation of significantly higher gnrh-I mRNA in the POA+H of rock hind males as compared to females suggests differential regulation of the gnrh-I transcripts in the two sexes of this protogynous species. In male E. adscensionis, but not in females, a negative relationship was seen between plasma 11-ketotestosterone (11-KT) and the v1a1 receptor mRNA levels in the POA+H, while a positive trend was observed between 11-KT and v1a2 receptor mRNA levels, indicating that these receptor forms may be differentially regulated. PMID- 26361871 TI - Synthesis, metabolism and systemic transport of a fluorinated mimic of the endogenous jasmonate precursor OPC-8:0. AB - Jasmonates (JAs) are fatty acid derivatives that mediate many developmental processes and stress responses in plants. Synthetic jasmonate derivatives (commonly isotopically labeled), which mimic the action of the endogenous compounds are often employed as internal standards or probes to study metabolic processes. However, stable-isotope labeling of jasmonates does not allow the study of spatial and temporal distribution of these compounds in real time by positron emission tomography (PET). In this study, we explore whether a fluorinated jasmonate could mimic the action of the endogenous compound and therefore, be later employed as a tracer to study metabolic processes by PET. We describe the synthesis and the metabolism of (Z)-7-fluoro-8-(3-oxo-2-(pent-2-en-1 yl)cyclopentyl)octanoic acid (7F-OPC-8:0), a fluorinated analog of the JA precursor OPC-8:0. Like endogenous jasmonates, 7F-OPC-8:0 induces the transcription of marker jasmonate responsive genes (JRG) and the accumulation of jasmonates after its application to Arabidopsis thaliana plants. By using UHPLC MS/MS, we could show that 7F-OPC-8:0 is metabolized in vivo similarly to the endogenous OPC-8:0. Furthermore, the fluorinated analog was successfully employed as a probe to show its translocation to undamaged systemic leaves when it was applied to wounded leaves. This result suggests that OPC-8:0 - and maybe other oxylipins - may contribute to the mobile signal which triggers systemic defense responses in plants. We highlight the potential of fluorinated oxylipins to study the mode of action of lipid-derived molecules in planta, either by conventional analytical methods or fluorine-based detection techniques. PMID- 26361872 TI - Lipogenesis mitigates dysregulated sarcoplasmic reticulum calcium uptake in muscular dystrophy. AB - Muscular dystrophy is accompanied by a reduction in activity of sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA) that contributes to abnormal Ca(2+) homeostasis in sarco/endoplasmic reticulum (SR/ER). Recent findings suggest that skeletal muscle fatty acid synthase (FAS) modulates SERCA activity and muscle function via its effects on SR membrane phospholipids. In this study, we examined muscle's lipid metabolism in mdx mice, a mouse model for Duchenne muscular dystrophy (DMD). De novo lipogenesis was ~50% reduced in mdx muscles compared to wildtype (WT) muscles. Gene expressions of lipogenic and other ER lipid-modifying enzymes were found to be differentially expressed between wildtype (WT) and mdx muscles. A comprehensive examination of muscles' SR phospholipidome revealed elevated phosphatidylcholine (PC) and PC/phosphatidylethanolamine (PE) ratio in mdx compared to WT mice. Studies in primary myocytes suggested that defects in key lipogenic enzymes including FAS, stearoyl-CoA desaturase-1 (SCD1), and Lipin1 are likely contributing to reduced SERCA activity in mdx mice. Triple transgenic expression of FAS, SCD1, and Lipin1 (3TG) in mdx myocytes partly rescued SERCA activity, which coincided with an increase in SR PE that normalized PC/PE ratio. These findings implicate a defect in lipogenesis to be a contributing factor for SERCA dysfunction in muscular dystrophy. Restoration of muscle's lipogenic pathway appears to mitigate SERCA function through its effects on SR membrane composition. PMID- 26361873 TI - A genetic variant of cortactin linked to acute lung injury impairs lamellipodia dynamics and endothelial wound healing. AB - Inflammatory mediators released in acute lung injury (ALI) trigger the disruption of interendothelial junctions, leading to loss of vascular barrier function, protein-rich pulmonary edema, and severe hypoxemia. Genetic signatures that predict patient recovery or disease progression are poorly defined, but recent genetic screening of ALI patients has identified an association between lung inflammatory disease and a single nucleotide polymorphism (SNP) in the gene for the actin-binding and barrier-regulatory protein cortactin. This study investigated the impact of this disease-linked cortactin variant on wound healing processes that may contribute to endothelial barrier restoration. A microfabricated platform was used to quantify wound healing in terms of gap closure speed, lamellipodia dynamics, and cell velocity. Overexpression of wild type cortactin in endothelial cells (ECs) improved directional cell motility and enhanced lamellipodial protrusion length, resulting in enhanced gap closure rates. By contrast, the cortactin SNP impaired wound closure and cell locomotion, consistent with the observed reduction in lamellipodial protrusion length and persistence. Overexpression of the cortactin SNP in lung ECs mitigated the barrier-enhancing activity of sphingosine 1-phosphate. These findings suggest that this common cortactin variant may functionally contribute to ALI predisposition by impeding endothelial wound healing. PMID- 26361876 TI - Recent advances in the mechanisms of lung alveolarization and the pathogenesis of bronchopulmonary dysplasia. AB - Alveolarization is the process by which the alveoli, the principal gas exchange units of the lung, are formed. Along with the maturation of the pulmonary vasculature, alveolarization is the objective of late lung development. The terminal airspaces that were formed during early lung development are divided by the process of secondary septation, progressively generating an increasing number of alveoli that are of smaller size, which substantially increases the surface area over which gas exchange can take place. Disturbances to alveolarization occur in bronchopulmonary dysplasia (BPD), which can be complicated by perturbations to the pulmonary vasculature that are associated with the development of pulmonary hypertension. Disturbances to lung development may also occur in persistent pulmonary hypertension of the newborn in term newborn infants, as well as in patients with congenital diaphragmatic hernia. These disturbances can lead to the formation of lungs with fewer and larger alveoli and a dysmorphic pulmonary vasculature. Consequently, affected lungs exhibit a reduced capacity for gas exchange, with important implications for morbidity and mortality in the immediate postnatal period and respiratory health consequences that may persist into adulthood. It is the objective of this Perspectives article to update the reader about recent developments in our understanding of the molecular mechanisms of alveolarization and the pathogenesis of BPD. PMID- 26361875 TI - SGLT inhibitors attenuate NO-dependent vascular relaxation in the pulmonary artery but not in the coronary artery. AB - Inhibitors of sodium-glucose cotransporter (SGLT)2 are a new class of oral drugs for type 2 diabetic patients that reduce plasma glucose levels by inhibiting renal glucose reabsorption. There is increasing evidence showing the beneficial effect of SGLT2 inhibitors on glucose control; however, less information is available regarding the impact of SGLT2 inhibitors on cardiovascular outcomes. The present study was designed to determine whether SGLT inhibitors regulate vascular relaxation in mouse pulmonary and coronary arteries. Phlorizin (a nonspecific SGLT inhibitor) and canagliflozin (a SGLT2-specific inhibitor) relaxed pulmonary arteries in a dose-dependent manner, but they had little or no effect on coronary arteries. Pretreatment with phlorizin or canagliflozin significantly inhibited sodium nitroprusside (SNP; a nitric oxide donor)-induced vascular relaxation in pulmonary arteries but not in coronary arteries. Phlorizin had no effect on cGMP-dependent relaxation in pulmonary arteries. SNP induced membrane hyperpolarization in human pulmonary artery smooth muscle cells, and pretreatment of cells with phlorizin and canagliflozin attenuated SNP-induced membrane hyperpolarization by decreasing K(+) activities induced by SNP. Contrary to the result observed in ex vivo experiments with SGLT inhibitors, SNP-dependent relaxation in pulmonary arteries was not altered by chronic administration of canagliflozin. On the other hand, canagliflozin administration significantly enhanced SNP-dependent relaxation in coronary arteries in diabetic mice. These data suggest that SGLT inhibitors differentially regulate vascular relaxation depending on the type of arteries, duration of the treatment, and health condition, such as diabetes. PMID- 26361874 TI - Circadian molecular clock in lung pathophysiology. AB - Disrupted daily or circadian rhythms of lung function and inflammatory responses are common features of chronic airway diseases. At the molecular level these circadian rhythms depend on the activity of an autoregulatory feedback loop oscillator of clock gene transcription factors, including the BMAL1:CLOCK activator complex and the repressors PERIOD and CRYPTOCHROME. The key nuclear receptors and transcription factors REV-ERBalpha and RORalpha regulate Bmal1 expression and provide stability to the oscillator. Circadian clock dysfunction is implicated in both immune and inflammatory responses to environmental, inflammatory, and infectious agents. Molecular clock function is altered by exposomes, tobacco smoke, lipopolysaccharide, hyperoxia, allergens, bleomycin, as well as bacterial and viral infections. The deacetylase Sirtuin 1 (SIRT1) regulates the timing of the clock through acetylation of BMAL1 and PER2 and controls the clock-dependent functions, which can also be affected by environmental stressors. Environmental agents and redox modulation may alter the levels of REV-ERBalpha and RORalpha in lung tissue in association with a heightened DNA damage response, cellular senescence, and inflammation. A reciprocal relationship exists between the molecular clock and immune/inflammatory responses in the lungs. Molecular clock function in lung cells may be used as a biomarker of disease severity and exacerbations or for assessing the efficacy of chronotherapy for disease management. Here, we provide a comprehensive overview of clock-controlled cellular and molecular functions in the lungs and highlight the repercussions of clock disruption on the pathophysiology of chronic airway diseases and their exacerbations. Furthermore, we highlight the potential for the molecular clock as a novel chronopharmacological target for the management of lung pathophysiology. PMID- 26361878 TI - Bone loss in patients with early inflammatory back pain suggestive of spondyloarthritis: results from the prospective DESIR cohort. AB - OBJECTIVES: The objectives of the study were to assess the 2 year BMD changes and their determinants in patients with early inflammatory back pain suggestive of axial spondyloarthritis (SpA) (DESIR cohort). METHODS: A total of 265 patients (54% male, mean age 34.4 years) had BMD measurements at baseline and at 2 years. Low BMD was defined as a Z score <=-2 (at at least one site) and significant bone loss was defined by a decrease in BMD >=0.03 g/cm(2). Clinical, biological and imaging parameters were assessed over 2 years. RESULTS: Thirty-nine patients (14.7%) had low BMD at baseline; 112 patients (42.3%) had a 2 year significant bone loss. One hundred and eighty-seven (70.6%) used NSAIDs at baseline and 89 (33.6%) received anti-TNF therapy over 2 years. In anti-TNF users, BMD significantly increased at the lumbar spine and did not change at the hip site from baseline. In multivariate analysis, baseline use of NSAIDs [odds ratio (OR) 0.38, P = 0.006] had a protective effect on hip bone loss. In patients without anti-TNF treatments, baseline use of NSAIDs (OR 0.09, P = 0.006) and a 2 year increase in BMI (OR 0.55, P = 0.003) had protective effects on hip bone loss, whereas a 2 year increase in fat mass was associated with hip bone loss (OR 1.18, P = 0.046). CONCLUSION: Among patients with symptoms suggestive of early axial SpA, 42.3% of patients have significant bone loss over 2 years. Anti-TNF therapy is protective against bone loss and baseline use of NSAIDs has a protective effect on hip bone loss. PMID- 26361877 TI - Can maternal DHA supplementation offer long-term protection against neonatal hyperoxic lung injury? AB - The effect of adverse perinatal environment (like maternal infection) has long standing effects on many organ systems, including the respiratory system. Use of maternal nutritional supplements is an exciting therapeutic option that could be used to protect the developing fetus. In a recent issue of the journal, Ali and associates (Ali M, Heyob KM, Velten M, Tipple TE, Rogers LK. Am J Physiol Lung Cell Mol Physiol 309: L441-L448, 2015) specifically look at maternal docosahexaenoic acid (DHA) supplementation and its effect on chronic apoptosis in the lung in a mouse model of perinatal inflammation and postnatal hyperoxia. Strikingly, the authors show that pulmonary apoptosis was augmented even 8 wk after the hyperoxia-exposed mice had been returned to room air. This effect was significantly attenuated in mice that were subjected to maternal dietary DHA supplementation. These findings are novel, significantly advance our understanding of chronic effects of adverse perinatal and neonatal events on the developing lung, and thereby offer novel therapeutic options in the form of maternal dietary supplementation with DHA. This editorial reviews the long-term effects of adverse perinatal environment on postnatal lung development and the protective effects of dietary supplements such as DHA. PMID- 26361879 TI - Two-year radiographic and clinical outcomes from the Canadian Methotrexate and Etanercept Outcome study in patients with rheumatoid arthritis. AB - OBJECTIVE: To evaluate radiographic and clinical outcomes up to 24 months in patients with RA enrolled in the Canadian Methotrexate and Etanercept Outcome study. METHODS: In this open-label non-inferiority trial, patients with inadequate response to MTX received etanercept plus MTX for 6 months and then were randomized to either etanercept monotherapy or continued etanercept plus MTX until 24 months. Radiographic data were analysed using the modified total Sharp score (mTSS), joint space narrowing and erosion scores. Secondary outcomes included the 28-joint DAS with ESR (DAS28-ESR), Simplified Disease Activity Index, Clinical Disease Activity Index, HAQ Disability Index (HAQ-DI) and safety. RESULTS: Two hundred five of 258 patients enrolled were randomized (98 etanercept, 107 etanercept plus MTX). At month 24, the mean increase from baseline to month 24 for the etanercept and etanercept plus MTX arms, respectively, for the mTSS were 0.4 (s.d. 1.9) and 0.0 (s.d. 1.4); for joint space narrowing, 0.1 (s.d. 0.6) and 0.0 (s.d. 0.7) and for erosion, 0.3 (s.d. 1.5) and 0.0 (s.d. 1.0). At month 24, the mean increase from month 6 mean scores/count increases for DAS28-ESR were 0.56 (s.d. 1.26) and 0.08 (s.d. 1.50); for Simplified Disease Activity Index, 4.7 (s.d. 13.1) and 0.9 (s.d. 12.5); for Clinical Disease Activity Index, 4.1 (s.d. 12.3) and 1.0 (s.d. 12.3) and for HAQ DI, 0.20 (s.d. 0.45) and 0.02 (s.d. 0.54). Patients with DAS28-ESR low disease activity (LDA)/remission at month 6 had numerically better outcomes at month 24 than patients with moderate to high disease activity at month 6. In patients with LDA/remission at month 6, outcomes were similar at month 24 between etanercept monotherapy and etanercept plus MTX, whereas patients with moderate to high disease activity at month 6 had numerically better outcomes with etanercept plus MTX than etanercept at month 24. There were no new safety signals and serious adverse events were not different between groups. CONCLUSION: These results support the possibility of discontinuing MTX in patients who have tolerability issues with MTX if they achieve LDA/remission. TRIAL REGISTRATION: ClinicalTrials.gov (https://clinicaltrials.gov/; NCT00654368). PMID- 26361880 TI - Metabolomics in rheumatology. PMID- 26361881 TI - Coping styles and disability in patients with hand osteoarthritis. AB - OBJECTIVE: Coping responses have been shown to determine health outcomes in chronic diseases. The aim of the study was to examine the role of joint-specific factors and coping styles on disability in patients with hand OA. METHODS: Primary hand OA patients who consulted secondary care, underwent physical examination to assess the number of joints with bony joint enlargements, pain upon palpation, soft tissue swelling, deformities and limitations in motion. Coping styles were assessed with Coping with Rheumatic Stressors. Disability (score >=5) was assessed by the Functional Index for Hand OA (possible score 0 30) cross-sectionally and after 1 year. With multivariate logistic regression, joint-specific variables and coping styles were associated with disability cross sectionally and after 1 year, adjusted for age, sex and BMI. RESULTS: A total of 314 patients (88% women, mean age 61.4 years) were included in the cross sectional analyses; 68% were considered as disabled. Longitudinal data after 1 year were available in 173 patients (71% disabled). In multivariate analysis including all joint-specific factors, only painful joints and joints with limitations in motion were associated with disability. Disadvantageous scores for the coping scales (comforting cognitions, decreasing activity and pacing) were positively associated with disability cross-sectionally. Disability after 1 year was only associated with the coping scales decreasing activity and pacing. Joint specific factors were also associated with disability, independent of coping styles. CONCLUSION: In patients with hand OA, joint-specific factors and coping styles decreasing activity and pacing were both associated with disability. Our results suggest that interventions should aim at joint-specific complaints as well as changing coping styles to improve functional outcome. PMID- 26361883 TI - Cardiac involvement in relapsing polychondritis in Japan. PMID- 26361882 TI - Recommendations for the conduct of efficacy trials of treatment devices for osteoarthritis: a report from a working group of the Arthritis Research UK Osteoarthritis and Crystal Diseases Clinical Studies Group. AB - OBJECTIVE: There are unique challenges to designing and carrying out high-quality trials testing therapeutic devices in OA and other rheumatic diseases. Such challenges include determining the mechanisms of action of the device and the appropriate sham. Design of device trials is more challenging than that of placebo-controlled drug trials. Our aim was to develop recommendations for designing device trials. METHODS: An Arthritis Research UK study group comprised of 30 rheumatologists, physiotherapists, podiatrists, engineers, orthopaedists, trialists and patients, including many who have carried out device trials, met and (using a Delphi-styled approach) came to consensus on recommendations for device trials. RESULTS: Challenges unique to device trials include defining the mechanism of action of the device and, therefore, the appropriate sham that provides a placebo effect without duplicating the action of the active device. Should there be no clear-cut mechanism of action, a three-arm trial including a no-treatment arm and one with presumed sham action was recommended. For individualized devices, generalizable indications and standardization of the devices are needed so that treatments can be generalized. CONCLUSION: A consensus set of recommendations for device trials was developed, providing a basis for improved trial design, and hopefully improvement in the number of effective therapeutic devices for rheumatic diseases. PMID- 26361884 TI - Secondary neoplasms arising from nevus sebaceus: A retrospective study of 450 cases in Taiwan. AB - Nevus sebaceus is frequently associated with the development of secondary neoplasms. Incidences of malignant transformation vary among different reports and few data is available regarding Asian populations. We aimed to determine the characteristics of secondary tumors developing from nevus sebaceus in a Taiwanese population and to review the published work. Patients with clinically and histologically confirmed nevus sebaceus were identified from 1992 to 2012 in a medical center. Among the 450 cases of nevus sebaceus, 38 secondary neoplasms were noted, accounting for 8.5% of all cases. Benign tumors represented more than 80% of all tumors. Syringocystadenoma papilliferum (2.7%) was the most common benign tumor, followed by trichoblastoma (1.6%) and trichilemmoma (1.6%) whereas basal cell carcinoma (0.9%) was the most frequent malignant tumor on nevus sebaceus and its clinical features were not typical. All the malignant tumors on nevus sebaceus were noted only in adulthood and the mean age of those with basal cell carcinoma was significantly older than that of trichoblastoma (P = 0.028). Our study concludes that malignant transformation is rare in nevus sebaceus and occurs uniquely in adulthood. On the basis of the findings, prophylactic excision of nevus sebaceus can be elective during childhood but is strongly advocated at puberty due to the increased risk of malignant transformation with time. PMID- 26361886 TI - Therapeutic hypothermia applicable to cardiac surgery. AB - OBJECTIVE: To review the beneficial and adverse effects of therapeutic hypothermia (TH) applicable to cardiac surgery with cardiopulmonary bypass (CPB) in the contexts of various temperature levels and techniques for achieving TH. DATABASES USED: Multiple electronic literature searches were performed using PubMed and Google for articles published from June 2012 to December 2014. Relevant terms (e.g. 'hypothermia', 'cardiopulmonary bypass', 'cardiac surgery', 'neuroprotection') were used to search for original articles, letters and reviews without species limitation. Reviews were included despite potential publication bias. References from the studies identified were also searched to find other potentially relevant citations. Abstracts, case reports, conference presentations, editorials and expert opinions were excluded. CONCLUSIONS: Therapeutic hypothermia is an essential measure of neuroprotection during cardiac surgery that may be achieved most effectively by intravascular cooling using hypothermic CPB. For most cardiac surgical procedures, mild to modest (32-36 degrees C) TH will be sufficient to assure neuroprotection and will avoid most of the adverse effects of hypothermia that occur at lower body core temperatures. PMID- 26361885 TI - ZmZHOUPI, an endosperm-specific basic helix-loop-helix transcription factor involved in maize seed development. AB - In angiosperm seeds the embryo is embedded within the endosperm, which is in turn enveloped by the seed coat, making inter-compartmental communication essential for coordinated seed growth. In this context the basic helix-loop-helix domain transcription factor AtZHOUPI (AtZOU) fulfils a key role in both the lysis of the transient endosperm and in embryo cuticle formation in Arabidopsis thaliana. In maize (Zea mays), a cereal with a persistent endosperm, a single gene, ZmZOU, falls into the same phylogenetic clade as AtZOU. Its expression is limited to the endosperm where it peaks during the filling stage. In ZmZOU-RNA interference knock-down lines embryo size is slightly reduced and the embryonic suspensor and the adjacent embryo surrounding region show retarded breakdown. Ectopic expression of ZmZOU reduces stomatal number, possibly due to inappropriate protein interactions. ZmZOU forms functional heterodimers with AtICE/AtSCREAM and the closely related maize proteins ZmICEb and ZmICEc, but its interaction is more efficient with the ZmICEa protein, which shows sequence divergence and only has close homologues in other monocotyledonous species. Consistent with the observation that these complexes can trans-activate target gene promoters from Arabidopsis, ZmZOU partially complements the Atzou-4 mutant. However, structural, trans-activation and gene expression data support the hypothesis that ZmZOU and ZmICEa may have coevolved to form a functional complex unique to monocot seeds. This divergence may explain the reduced functionality of ZmZOU in Arabidopsis, and reflect functional specificities which are unique to the monocotyledon lineage. PMID- 26361887 TI - NF-kappaB-dependent signals control BOB.1/OBF.1 and Oct2 transcriptional activity in B cells. AB - The transcriptional co-activator BOB.1/OBF.1 is crucial for Octamer-driven transcription in B cells. BOB.1/OBF.1-deficiency leads to tremendous defects in B cell development and function. Therefore, in the past research focused on the identification of BOB.1/OBF.1 target genes. However, the regulation of BOB.1/OBF.1 expression itself is poorly understood. Here we show that in B cells NF-kappaB as well as to some extent NFAT proteins are involved in the activation of basal as well as inducible BOB.1/OBF.1 expression by direct binding to the BOB.1/OBF.1 promoter. Moreover, the analysis of different inducers of NF-kappaB, like several TLR ligands, TNF-alpha, BAFF, or LTalpha1beta2, revealed that both the canonical and noncanonical NF-kappaB pathways are involved in the induction of BOB.1/OBF.1 gene. The identification of so far unknown inducers that regulate BOB.1/OBF.1 expression in B cells provides novel insights in the potential function of BOB.1/OBF.1 during different aspects of B-cell development and function. PMID- 26361888 TI - The E3 ligase Itch knockout mice show hyperproliferation and wound healing alteration. AB - The HECT-type E3 ubiquitin ligase Itch is absent in the non-agouti-lethal 18H or Itchy mice, which develop a severe immunological disease. Several of the known Itch substrates are relevant for epidermal development and homeostasis, such as p63, Notch, c-Jun and JunB. By analysing Itchy mice before the onset of immunological alterations, we investigated the contribution of Itch in skin development and wound healing. Itchy newborn mice manifested hyperplastic epidermis, which is not present in adulthood. Itch(-/-) cultured keratinocytes showed overexpression of proliferating markers and increased capability to proliferate, migrate and to repair a scratch injury in vitro. These data correlated with improved in vivo wound healing in Itchy mice, at late time points of the repair process when Itch is physiologically upregulated. Despite healing acceleration, epidermal remodelling was delayed in the scars of Itch(-/-) mice, as indicated by enhanced epidermal thickening, keratinocyte proliferation and keratin 6 expression, and retarded keratin 14 polarization to the basal layer. Itch(-/-) keratinocyte prolonged activation was not associated with increased immune cell persistence in the scars. Our in vitro and in vivo results indicate that Itch plays a role in epidermal homeostasis and remodelling and this feature does not seem to depend on immunological alterations. PMID- 26361889 TI - Assessment of the acute effects of glucocorticoid treatment on coronary microembolization using cine, first-pass perfusion, and delayed enhancement MRI. AB - PURPOSE: To assess the acute effects of methylprednisone treatment (MPT) on coronary microembolization (CME) by cardiac cine, first-pass perfusion, and delayed gadolinium enhancement magnetic resonance imaging (DE-MRI) in an experimental swine model. MATERIALS AND METHODS: Microembolization was established by intracoronary infusion of microspheres into the left anterior artery. Swine received placebo (n = 12) or methylprednisolone (n = 10, 30 mg/kg) intravenously 30 minutes before microembolization. Perfusion and DE-MRI was performed 6 hours after microembolization. Cine MR images of pre-/post-CME were obtained using 1.5T scanner. RESULTS: Cine MRI demonstrated relative amelioration of the post-CME myocardial contractile dysfunction in the glucocorticoid-treated group compared to the placebo group (P < 0.001). Post-CME target myocardial perfusion parameters decreased in both groups after microembolization. The extent of these decreases were the same for the embolized-to-control area ratio of maximum upslope (P = 0.245; 95% confidence interval of the difference [CID], 0.041/0.148) and time to peak ratio (P = 0.122; 95% CID, -0.201/0.026); however, the maximum signal intensity was higher in the glucocorticoid-treated group (P = 0.012; 95% CID, 0.023/0.156). DE-MRI revealed patchy hyperenhancement in all placebo pigs (n = 12/12) after microembolization, but no hyperenhanced regions in the glucocorticoid-pretreated pigs (n = 0/10). CONCLUSION: Standard, readily available, cardiac MRI techniques are useful in demonstrating post-CME myocardial dysfunction and the acute effects of glucocorticoid treatment on CME. Glucocorticoid pretreatment improves myocardial contractile dysfunction, prevents hyperenhancement, and partially ameliorates the decline of myocardial perfusion in the embolized area. PMID- 26361890 TI - Chlorhexidine-induced anaphylaxis in surgical patients: a review of the literature. AB - BACKGROUND: Chlorhexidine (CHL) has antiseptic and disinfectant properties used to prevent hospital-acquired infections. CHL-induced anaphylaxis is poorly reported in surgical literature despite government warnings and growing recognition. The aim of this review is to increase awareness of CHL-induced anaphylaxis in the surgical population. METHODS: Literature review of Embase, Medline, PubMed and the Cochrane library using 'anaphylaxis (and) chlorhexidine' search terms. RESULTS: Thirty-six articles were published on surgical patients suffering anaphylaxis to CHL. Within these, seven patients had two proven separate anaphylactic reactions and one had three separate proven anaphylactic reactions. The most commonly affected speciality was urology. The majority occurred during elective procedures. A history of atopy was surprisingly uncommon as was bronchospasm. Six patients required active chest compressions and 39.71% of patients had their surgical procedure abandoned. Unplanned intensive care admissions occurred in 27.94%. DISCUSSION: In order to reduce abandoned procedures, unplanned intensive care unit admissions, morbidity and mortality associated with CHL-induced anaphylaxis we recommend the following: rationalization of CHL-containing products, greater vigilance regarding subtle symptoms of CHL allergy, appropriate investigation of these symptoms and a greater awareness of CHL-containing products. Lastly, we outline the appropriate investigations and highlight the need for meticulous documentation in those who are CHL allergic. PMID- 26361891 TI - Developmental time course of peripheral cross-modal sensory interaction of the trigeminal and gustatory systems. AB - Few sensory modalities appear to engage in cross-modal interactions within the peripheral nervous system, making the integrated relationship between the peripheral gustatory and trigeminal systems an ideal model for investigating cross-sensory support. The present study examined taste system anatomy following unilateral transection of the trigeminal lingual nerve (LX) while leaving the gustatory chorda tympani intact. At 10, 25, or 65 days of age, rats underwent LX with outcomes assessed following various survival times. Fungiform papillae were classified by morphological feature using surface analysis. Taste bud volumes were calculated from histological sections of the anterior tongue. Differences in papillae morphology were evident by 2 days post-transection of P10 rats and by 8 days post in P25 rats. When transected at P65, animals never exhibited statistically significant morphological changes. After LX at P10, fewer taste buds were present on the transected side following 16 and 24 days survival time and remaining taste buds were smaller than on the intact side. In P25 and P65 animals, taste bud volumes were reduced on the denervated side by 8 and 16 days postsurgery, respectively. By 50 days post-transection, taste buds of P10 animals had not recovered in size; however, all observed changes in papillae morphology and taste buds subsided in P25 and P65 rats. Results indicate that LX impacts taste receptor cells and alters epithelial morphology of fungiform papillae, particularly during early development. These findings highlight dual roles for the lingual nerve in the maintenance of both gustatory and non-gustatory tissues on the anterior tongue. PMID- 26361893 TI - Effects of time-of-day on neuromuscular function in untrained men: Specific responses of high morning performers and high evening performers. AB - It has been clearly established that maximal force varies during the day in human muscles but the exact mechanisms behind the diurnal rhythms are still not fully clarified. Therefore, the aim of this study was to examine the diurnal rhythms in maximal isometric force production in a large group of participants and also by separating the high morning performance types (n = 8) and the high evening performance types (n = 19) from the neutral types (n = 45) based on their actual maximal isometric force levels. Measurements were performed in the morning (7:26 h +/- 63 min) and in the evening (17:57 h +/- 74 min) for maximal bilateral isometric leg press force (MVCLP) together with myoelectric activity (EMGLP), maximal unilateral isometric knee extension force (MVCKE) and maximal voluntary activation level (VA%) during maximal unilateral isometric knee extension force (MVCVA) together with myoelectric activity (EMGVA). In addition, venous blood samples were drawn four times a day and serum testosterone and cortisol concentrations were analyzed. None of the participants belonged to the extreme morning or evening chronotype according to the Munich Chronotype Questionnaire. In the total group of participants, MVCLP and MVCKE were 4.4 +/- 12.9% (p < 0.01) and 4.3 +/- 10.6% (p < 0.01) higher in the evening compared to the morning. MVCVA and VA% did not show significant diurnal variation. The high morning performance types showed lower force values in the evening compared to the morning for MVCLP (10.8 +/- 9.1%; p < 0.05) and MVCKE (5.7 +/- 4.9%; p < 0.05). No significant diurnal variation was observed for MVCVA and VA%. The high evening performance types showed higher force values in the evening for MVCLP (16.1 +/- 15.9%; p < 0.001), MVCKE (13.5 +/- 11.3%; p < 0.001) and MVCVA (6.2 +/- 9.9%; p < 0.05) with a concomitant higher VA% in the evening (p < 0.05). The neutral types showed significantly higher evening force values for the MVCLP (2.1 +/- 6.7%; p < 0.05). All the other neuromuscular variables did not show significant diurnal variations. EMGLP and EMGVA did not show significant diurnal fluctuations in any group. Serum testosterone and cortisol concentrations showed normal daily rhythms with higher values observed in the morning in all of the groups (p < 0.001). Between-group differences were observed for MVCLP (p < 0.001) and MVCKE (p < 0.001) between all of the three groups. Diurnal changes in VA% differed between the high evening performance types and the neutral types (p < 0.05) and the testosterone/cortisol ratio (p < 0.05) as well as vastus lateralis EMGVA (p < 0.05) differed between the high morning and high evening performance types. In conclusion, we were able to identify the high morning performance types, the high evening performance types and the neutral types who showed significantly different diurnal rhythms in force production, irrespective of their actual chronotype. Therefore, the questionnaires designed to determine the chronotype may not always be sensitive enough to determine the "morningness" or "eveningness" in maximal neuromuscular performance. In general, central factors could partially explain the diurnal fluctuations in maximal strength performance, but peripheral mechanisms were also possibly involved. PMID- 26361892 TI - Simultaneous quantification of glutamate and glutamine by J-modulated spectroscopy at 3 Tesla. AB - PURPOSE: The echo time (TE) averaged spectrum is the one-dimensional (1D) cross section of the J-resolved spectrum at J = 0. In multiecho TE-averaged spectroscopy, glutamate (Glu) is differentiated from glutamine (Gln) at 3 Tesla (T). This method, however, almost entirely suppresses Gln resonance lines around 2.35 ppm, leaving Gln undetermined. This study presents a novel method for quantifying both Glu and Gln using multi-echo spectral data. METHODS: A 1D cross section of J-resolved spectroscopy at J = 7.5 Hz-referred to as J-modulated spectroscopy-was developed to simultaneously quantify Glu and Gln levels in the human brain. The transverse relaxation times (T2 s) of metabolites were first determined using conventional TE-averaged spectroscopy with different starting echo time and then incorporated into the spectral model for fitting J-modulated data. RESULTS: Simulation and in vivo data showed that the resonance signals of Glu and Gln were clearly separated around 2.35 ppm in J-modulated spectroscopy. In the anterior cingulate cortex, both Glu and Gln levels were found to be significantly higher in gray matter than in white matter in healthy subjects (P < 10(-10) and < 10(-5) , respectively). CONCLUSION: Gln resonances can be clearly separated from Glu and N-acetyl-aspartate around 2.35 ppm using J-modulated spectroscopy. This method can be used to quantitatively measure Glu and Gln simultaneously at 3T. Magn Reson Med 76:725-732, 2016. Published 2015. This article is a U.S. Government work and is in the public domain in the USA. PMID- 26361894 TI - Systematic Optimization of C-Terminal Amine-Based Isotope Labeling of Substrates Approach for Deep Screening of C-Terminome. AB - It is well-known that protein C-termini play important roles in various biological processes, and thus the precise characterization of C-termini is essential for fully elucidating protein structures and understanding protein functions. Although many efforts have been made in the field during the latest 2 decades, the progress is still far behind its counterpart, N-termini, and it necessitates more novel or optimized methods. Herein, we report an optimized C termini identification approach based on the C-terminal amine-based isotope labeling of substrates (C-TAILS) method. We optimized the amidation reaction conditions to achieve higher yield of fully amidated product. We evaluated different carboxyl and amine blocking reagents and found the superior performance of Ac-NHS and ethanolamine. Replacement of dimethylation with acetylation for Lys blocking resulted in the identification of 232 C-terminal peptides in an Escherichia coli sample, about 42% higher than the conventional C-TAILS. A systematic data analysis revealed that the optimized method is unbiased to the number of lysine in peptides, more reproducible and with higher MASCOT scores. Moreover, the introduction of the Single-Charge Ion Inclusion (SCII) method to alleviate the charge deficiency of small peptides allowed an additional 26% increase in identification number. With the optimized method, we identified 481 C terminal peptides corresponding to 369 C-termini in E. coli in a triplicate experiments using 80 MUg each. Our optimized method would benefit the deep screening of C-terminome and possibly help discover some novel C-terminal modifications. Data are available via ProteomeXchange with identifier PXD002409. PMID- 26361895 TI - Preface to Substance Use and Misuse Special 50th Anniversary Issue. PMID- 26361896 TI - Substance Use and Misuse Fifty Years Later: Ongoing Flaws and Unfinished Business. PMID- 26361897 TI - Disciplinary Prejudice: An Ever Present Flaw. PMID- 26361899 TI - The Exploitation of Drug Users. AB - Drug users have been exploited in research studies and clinical practice. We explore ways in which exploitation has occurred and strategies to help patients, research subjects and communities to prevent or avoid exploitation. PMID- 26361900 TI - Preventing Substance Use and Misuse Among Racial and Ethnic Minority Adolescents: Why Are We Not Addressing Discrimination in Prevention Programs? PMID- 26361901 TI - Substance Use Disorders, Evidence-Based Practices and the Possible Nature of Deep Flaws. PMID- 26361902 TI - Visual Images on the Covers of Scientific Journals and Books--Needed or Decorations? PMID- 26361903 TI - Witnessing Each Other: An Intersubjective Stance for Exhibitions Relating to Substance Use and Abuse. AB - Most exhibitions are conceived to convey information the experts making the exhibition believe other people need or want. But the notion that the intended exhibition public will cooperate with the exhibition organizers. intent disregards the reasons people come to exhibitions and the way they use them. While the author contends that an exhibition cannot use facts to convince someone to abstain from substances they crave, exhibitions can nonetheless make a difference in lives complicated by substance use by providing representation for voices that are rarely heard and building empathy between witness and witnessed. The purpose of such an endeavor is not to change attitudes or behaviors toward a pre-determined outcome, but to facilitate a witnessing of others. EXPERIENCE: The uniquely intersubjective medium of exhibition can thus succeed in this field by opening the potential of mutual, humanizing recognition among people with varied life experience of substance use and abuse. PMID- 26361904 TI - Retire the Concept of "Relapse". PMID- 26361905 TI - The Fear of Drugs Used by Strangers. PMID- 26361907 TI - "The Change That You Wish to See in the World". PMID- 26361906 TI - What the History of Drugs Can Teach Us About the Current Cannabis Legalization Process: Unfinished Business. AB - Over time, there have been considerable changes in the variety, availability, production, distribution, and use and user(s) of psychoactive substances, the meaning of substance use and its impact on users and their social or physical environment(s). This article reviews the mechanisms of introduction of psychoactive substances such as alcohol, tobacco, coffee, tea and cannabis to populations and communities that did not have them before. It considers the historical tension between early adopters who greet new substances with various levels of enthusiasm in their eagerness to enjoy what they believe to be the benefits of using these substances, and those focused on what they believe to be the negative aspects of use, who decry these new substances with horror. With more nonusers than users in the population, social policies tend to be directed at preventing, restricting, or punishing selected use, users and .drugs., using controls and interventions such regulation, incarceration, death sentence, treatment, prevention, legalization, taxation, among others. Whatever their intent or wished-for impact, all had consequences that produced additional, unplanned for, and (often) negative effects. This paper will consider some of these sequences as they occurred historically with other substances in light of the current shift to legalization and normalization of cannabis, noting the mechanisms of use, controls, and consequences of some types of formal interventions and give some attention to how and what we can learn from our experiences in order to plan ahead and become better prepared to successfully deal with the 'unexpecteds' of that well-known 'hell' paved with good intentions. PMID- 26361909 TI - Macro Social Flaws and Intervention's Unfinished Business: A Personal Note on Young People's Drug Use in Hong Kong. AB - This paper traces how social, economic, and cultural changes in Hong Kong in the past five decades might have affected the pattern of illicit drug use among young people in Hong Kong. The prevalence of illicit drug use by young people had been very low before the 1990s, and like adult users, young users mostly used heroin. This pattern of drug use started to change in the late 1990s, when there was a sudden upsurge of drug use among young people, and psychoactive drugs such as ketamine quickly replaced heroin as the most popular drugs among them. An attempt is made to explain the new pattern of young people's drug use with respect to the changes of the social, economic and cultural conditions of Hong Kong since the 1960s, making use of Beck's risk society perspective and Parker's concept of normalization of recreational drug use. The identification of macro social flaws points to the need to address societal factors impeding successful interventions, which will involve reducing the blockage of upward mobility for young people, and providing them with the latest scientific knowledge of the physical and mental damages of ketamine and other psychoactive drugs for their better understanding of the risk of drug use. PMID- 26361908 TI - Alcoholics Anonymous: Warts and All. PMID- 26361910 TI - The Evaluation of Substance User Treatment--A Jubilee Proposal for the 21st Century. AB - This article recommends a longitudinal, national study of the outcomes of substance user treatment, plus a cohort of users who do not enter treatment. Viewing addiction primarily as a brain disease has provided interesting descriptive information but dismisses the psychological, social, political, economic, and legal dimensions of substance user dependence. An increased emphasis on behavioral study of treatment outcomes with a decreased emphasis on brain-focused research on substance use is overdue. PMID- 26361911 TI - Why Mathematical Computer Simulations Are the New Laboratory for Scientists. AB - In this paper, we introduce a new powerful scientific paradigm to understand natural and cultural processes. This new paradigm is based on two fundamental keywords: Data, as representative sample of the process we need to analyze, and Artificial Adaptive Systems, as a new mathematical technique able to make explicit the nonlinearity embedded in the process. We will try to make explicit these concepts analyzing how the distribution of events into the physical space may reveal the hidden logic connecting these events together. PMID- 26361912 TI - The Unspoken Shift From Quality to Quantity Standards In Substance Use(r) Treatment and Prevention: A Challenge to Unfinished Intervention Business. AB - A common flaw when dealing with substance use and misuse is the over-inclination to (re)-act; a reflexive "knee-jerk" and not a well-planned act which is theoretically and empirically informed. It seems that a shift from quantity driven standards back to quality-driven standards would be best achieved by encouraging politicians, stock holders, and decision makers to question more, before financially supporting any prevention intervention. PMID- 26361913 TI - "The Gold Standard" and Related Considerations for a Maturing Science of Substance Abuse Treatment. Therapeutic Communities; A Case in Point. AB - The randomized control trial (RCT) is commonly celebrated as the "Gold Standard" of research designs. However, such evidentiary distinctions contain serious implications for the scientific acceptance, funding, and public perception of various treatments for substance abuse. This issue and related considerations are briefly discussed from the perspective of therapeutic community treatment and research. PMID- 26361914 TI - Diffusion of Evidence-Based Interventions in HIV and Substance User Programs: Flaws and Lessons From the Sub-Saharan African Region. AB - The time has come that Sub-Saharan Africa benefit from implementation of Evidence Based Interventions (EBIs) that have been developed over time in the United States, Europe, and by the United Nations (UN) agencies. This paper has been written partly because less information is coming out of Africa regarding diffusion and implementation of EBIs. There is a need to highlight and reflect on the delivery of interventions of human immunodeficiency virus (HIV) and substance use(r) programs in Sub-Saharan Africa. Both the evidence and practices may help enrich discussions as a way to improve the quality of program outcome in the region and at the same time retire inappropriate old interventions "Prevention can work, but not everything called prevention works" Belinda E. Sims (2011). PMID- 26361915 TI - Controlling, Modeling, Consensus, and Substance Use(r) Policy Intervention: Unfinished Business. AB - This article looks at certain aspects of unfinished business in substance use policy from the economist's perspective. It takes the view that in tackling a policy issue such as cigarette smoking, it is likely to be necessary to use a portfolio of policy tools, rather than on just one tool, and that it is likely to be necessary to accept that complete elimination of the activity being considered will almost certainly cost more than it is worth-we will probably always have to live with some nonzero level of such activities. PMID- 26361916 TI - Unfinished Business or, Why Is It So Difficult to Implement an Evidence-Based Alcohol-Use Intervention Program? AB - Though many evidence-based interventions targeting adolescent alcohol drug use are available, it is unknown if these interventions are put to practice. In this article, we discuss some critical issues associated with the implementation of an evidence-based alcohol prevention program in the Netherlands. Tips that may potentially contribute to a successful implementation of this specific intervention are provided. PMID- 26361917 TI - Measuring Substance Use and Misuse via Survey Research: Unfinished Business. AB - This article reviews unfinished business regarding the assessment of substance use behaviors by using survey research methodologies, a practice that dates back to the earliest years of this journal's publication. Six classes of unfinished business are considered including errors of sampling, coverage, non-response, measurement, processing, and ethics. It may be that there is more now that we do not know than when this work began some 50 years ago. PMID- 26361918 TI - Success, Failure, and Unfinished Business of Education, Prevention, Policy, and Intervention Programs on Substance Misuse in Brazilian Sport. AB - The current Brazilian situation is such that it is difficult to obtain a worldwide evaluation of failure in education, intervention, or prevention programs. How fragile Brazil's anti-doping system is, its appropriateness as well as its relevance, with needed policy infrastructures for achieving the selected goals, and how wide the gap is between education and prevention program effectiveness between high-performance athletes and recreational practitioners who just want to look good. An additional concern, and ever present flaw regarding Brazil's "common sportsman" in day-to-day society is their not receiving known and necessary "sports education," enabling the development of an "at-risk" population for self-harm. Reflections on public health policy are noted. PMID- 26361919 TI - Drug Testing US Student-Athletes for Performance-Enhancing Substance Misuse: A Flawed Process. AB - The author argues that drug testing of U.S. high school students for performance enhancing substance misuse is invasive, expensive, and the low number of positive test results do not justify the costs, especially in financially strapped school districts where this money would be better spent on injury prevention for athletes and the education of all students. PMID- 26361920 TI - Nursing Care in Alcohol and Drug User Treatment Facilities. AB - Registered and advanced practice nurses are employed in substance user treatment facilities across the US and in most industrialized countries. Patterns of employment and job descriptions for nurses, however, are highly inconsistent and seriously flawed. Many regulatory system, legislative and government agency factors and to some degree, the nursing profession itself, sustain the flaws and limit the delivery of comprehensive care. Competencies linked to addictions nursing best practices are often underutilized because of narrow job descriptions. This results in limited health and nursing service delivery to vulnerable populations receiving treatment in these government funded programs. This article highlights the increasing demand for the delivery of integrated care to psychiatric and substance using populations. The author considers factors which stake holders can influence to change flawed employment patterns and limited access to comprehensive care for substance users. PMID- 26361921 TI - Junkies in the House of the Lord. AB - The self-organization and mobilization of active drugs users is historically four decades old, but is rarely noted in the addiction, or drug policy literature. This piece looks closely at three European countries that have had varying degrees of success in organizing injection drugs users as key stakeholders in the development of non-criminalizing drug and reintegrating social policies. Indeed, the core questions here are about whether drugs users organizations can, or do have any impact in the improvement of drug treatment as well as the policies, which ultimately govern their lives. It should be noted that all of the groups studied included a few ex-users and/or non-user allies. PMID- 26361922 TI - No More Waiting Lists. PMID- 26361923 TI - Broadening Substance Use(r) Research and Intervention Efforts to Address Context. PMID- 26361924 TI - The Public Health Dilemma in the Alcohol Intervention Area: Unfinished Business Between Limits and Freedom. PMID- 26361925 TI - U-turn Our Complacency in Dealing With the Potency of Alcohol. AB - This article argues that we need to reverse our complacency in dealing with alcohol, a drug that kills at least 2.7 million people worldwide annually. Ecological studies suggest that humans have evolved to be active and functional in relation to alcohol use; the present problem is that alcohol is too easily available in too potent a form. Toxicological analyses indicate that European adults consume, on average, 1,000 times the dose of alcohol that would normally be set for voluntary exposure to a consumed carcinogen. Political analyses find that a predominant driver of alcohol-related harm is the potency of business influence on policy making. Complacency would be reversed by compulsory warning labels that alcohol causes cancer; by holding producers accountable for the harm that their products cause; and, by governments moving toward a global legally binding agreement for alcohol. PMID- 26361926 TI - Development and Evaluation of Theories of Alcohol-Related Violence: Covering a 40 Year Span. PMID- 26361927 TI - Substance Use: A Police Practitioner's Perspective--More Cooperation Between Academics and Practitioners Is Needed. PMID- 26361928 TI - Images: A Puzzling First Glance Not Looking at the Glass-Looking at the Plate When an Image is better than truth. PMID- 26361929 TI - Evidence-Informed, Evidence not Used: A Pilot Study of a Sustained Flawed Process and Unfinished Business. AB - An anonymous, online survey using a convenience sample of global researchers was implemented during 2013-2014 to explore the actual use or nonuse of their research outcomes in a range of interventions in the area of substance use and related disorders. Eighty-seven researchers from 19 countries responded. Based on their self-reports, the utilizability of their findings were either unknown to them or had no effects in terms of substance use treatment, prevention, policies, or professional education. Most respondents did believe, however, that their investigations had an influence on substance use research. The study's limitations are noted. PMID- 26361930 TI - "Integrated interventions are dead. Long live sustainable integrated interventions!"--Austerity Challenges the Continuation of Effective Interventions in the Field of Drug Use-Related Harm Reduction. PMID- 26361931 TI - Considering Gender, Sexuality, 'Drugs,' Use(rs) and Nonuse(rs): Unfinished Business. PMID- 26361932 TI - Change Is a Process not a Product: Reflections on Pieces to the Puzzle. PMID- 26361933 TI - Drug Use(r) Concepts. PMID- 26361934 TI - An Ode to Unfinished 'Recovery'. PMID- 26361935 TI - Visual function test for early detection of ethambutol induced ocular toxicity at the subclinical level. AB - CONTEXT: Tuberculosis in developed countries is on the rise, and the main treatment ethambutol is known to induce ocular toxicity. However, to date, there are unknown tests or protocols for detecting subclinical ethambutol-induced ocular toxicity, which is important as early detection is related to symptom reversibility. We defined the ethambutol induced ocular toxicity as stastically siginificant change of visual function which was induced by ethambutol. OBJECTIVE: We aimed to identify a visual function test for the early detection of subclinical ethambutol-induced ocular toxicity. Furthermore, we also investigated the continuity or reversibility of early subclinical changes that were observed during the visual function tests after stopping ethambutol treatment. MATERIALS AND METHODS: The age range of 31 patients was from 13 to 72 years. The range of dosage was 15-19 mg/kg/day. The average period of dosage was 5 months. We performed a visual acuity test, visual field test, color vision test, contrast sensitivity test, fundus examination, retinal nerve fiver layer optical coherence tomography test (RNFL OCT) per month and pattern visual evoked potential test (pattern VEP) every 2 months before and during ethambutol treatment in 62 eyes of 31 patients. Among these patients, selected 21 patients were rexamined by these tests at the 3, 6 and 12 months after stopping ethambutol treatment. We compared the test results from the last follow-up during ethambutol treatment and after ethambutol stoppage with those obtained before ethambutol treatment (baseline). RESULTS: RNFL OCT showed that average RNFL thickness increased 5 months after ethambutol treatment (p = 0.032), and pattern VEP showed that P100 latency was delayed in 2 and 4 months after ethambutol treatment (p = 0.001; p < 0.001, respectively). These early changes observed on RNFL OCT and pattern VEP progressed 6 months after ethambutol stoppage in 21 patients. Twelve months after ethambutol stoppage, these early changes returned to baseline levels. During the study, no changes in visual acuity, color vision, fundus, contrast sensitivity or visual field were observed. CONCLUSIONS: Pattern VEP and RNFL OCT are suitable tests for the early detection of subclinical ethambutol-induced ocular toxicity. These tests should be performed until 12 months after ethambutol stoppage. PMID- 26361936 TI - Erratum to: Potential of promotion of alleles by genome editing to improve quantitative traits in livestock breeding programs. PMID- 26361937 TI - Maternal language and adverse birth outcomes in a statewide analysis. AB - Limited English proficiency is associated with disparities across diverse health outcomes. However, evidence regarding adverse birth outcomes across languages is limited, particularly among U.S. Asian and Pacific Islander populations. The study goal was to consider the relationship of maternal language to birth outcomes using statewide hospitalization data. Detailed discharge data from Hawaii childbirth hospitalizations from 2012 (n = 11,419) were compared by maternal language (English language or not) for adverse outcomes using descriptive and multivariable log-binomial regression models, controlling for race/ethnicity, age group, and payer. Ten percent of mothers spoke a language other than English; 93% of these spoke an Asian or Pacific Islander language. In multivariable models, compared to English speakers, non-English speakers had significantly higher risk (adjusted relative risk [ARR]: 2.02; 95% confidence interval [CI]: 1.34-3.04) of obstetric trauma in vaginal deliveries without instrumentation. Some significant variation was seen by language for other birth outcomes, including an increased rate of primary Caesarean sections and vaginal births after Caesarean, among non-English speakers. Non-English speakers had approximately two times higher risk of having an obstetric trauma during a vaginal birth when other factors, including race/ethnicity, were controlled. Non English speakers also had higher rates of potentially high-risk deliveries. PMID- 26361938 TI - Impact of dietary fiber/starch ratio in shaping caecal microbiota in rabbits. AB - The objective of this experiment was to determine whether changing the dietary neutral detergent fiber (NDF)/starch ratio affected caecal microbiota when 4 different diets (diet A: 2.3 NDF/starch, diet B: 1.9, diet C: 1.4, diet D: 1.0) were formulated. A total of 200 weaned rabbits (35 days old, 50 per group) were used for the experiment, which started after an adaptation period of 7 days (i.e., day 42). Caecal contents were obtained from rabbits fed different NDF/starch diets at 52, 62, 72, and 82 days of life. The bacterial community structure was characterized by high-throughput 16S rRNA sequencing. Firmicutes, Actinobacteria, Synergistetes, and Tenericutes did not significantly change with diet or age. However, Bacteroidetes (P < 0.05), Proteobacteria (P < 0.01), and Verrucomicrobia (P < 0.05) reads were significantly affected by diet, and Proteobacteria (P < 0.01) and Verrucomicrobia (P < 0.05) reads were significantly influenced by age. At the genus level, Escherichia/Shigella (P < 0.01) was overrepresented in diet A (high fiber) relative to diet D (high starch) in 52- and 62-day-old rabbits. Venn diagrams and heat map plot analyses revealed that the number of gut species shared between animals with different diet treatments increased with age. These results suggest that dietary fiber per starch ratios and age significantly alter the composition of caecal microbiota in growing rabbits. PMID- 26361939 TI - Functional level during the first 2 years after moderate and severe traumatic brain injury. AB - BACKGROUND: Long-term outcomes after TBI are examined to a large extent, but longitudinal studies with more than 1-year follow-up time after injury have been fewer in number. The course of recovery may vary due to a number of factors and it is still somewhat unclear which factors are contributing. AIM: The aim of this study was to describe the functional level at four time points up to 24 months after traumatic brain injury (TBI) and to evaluate the predictive impact of pre injury and injury-related factors. DESIGN: A cohort study. SETTING: Outpatient. POPULATION: Sixty-five patients with moderate (n = 21) or severe (n = 44) TBI. METHODS: The patients with TBI were examined with Functional Independence Measure (FIM) and Glasgow Outcome Scale Extended (GOSE) at 3 months, 12 months and 24 months after injury. Possible predictors were analysed in a regression model using FIM total score at 24 months as the outcome measure. RESULTS: FIM scores improved significantly from rehabilitation unit discharge to 24 months after injury, with peak levels at 3 and 24 months after injury (p < 0.001), for the whole TBI group and the group with severe TBI. The moderate TBI group did not show significant FIM score improvement during this time period. GOSE scores for the whole group and the moderate group improved significantly over time, but the severe group did not. FIM at admission to the rehabilitation unit and GCS score at admission to the rehabilitation unit were closest to being significant predictors of FIM total scores 24 months after injury (B = 0.265 and 2.883, R(2 )= 0.39, p = 0.073, p = 0.081). CONCLUSION: FIM levels improved during the period from rehabilitation unit discharge to 3 months follow-up; thereafter, there was a 'plateauing' of recovery. In contrast, GOSE 'plateauing' of recovery was at 12 months. CLINICAL REHABILITATION IMPACT: The study results may indicate that two of the most used outcome measures in TBI research are more relevant for assessment of the functional recovery in a sub-acute phase than in later stages of TBI recovery. PMID- 26361940 TI - Effect of treatment with myo-inositol on semen parameters of patients undergoing an IVF cycle: in vivo study. AB - INTRODUCTION: Myo-inositol (MI) is a precursor for the synthesis of phosphatidylinositol polyphosphates (PIPs). The aim of the study is to evaluate the effect of its administration on semen parameters of male patients undergoing an in vitro fertilization cycles. METHODS: In vivo study. Samples were semen of 62 patients divided into three different groups: healthy fertile patients (Group A); patients with oligoasthenospermia (OA) (Group B); control group (CTR). The collected samples were analyzed by optic microscopy in order to evaluate semen's volume, spermatozoa's number and motility before and after density-gradient separation method. These parameters were evaluated before and after administration of 4000 mg/die of MI and 400 ug of folic acid for 2 months. The results were analyzed statistically with Student's t-test. RESULTS: After treatment there was a significant increase of basal and after density-gradient separation method spermatozoa concentration in Group B, and a significant increase of spermatozoa count after density-gradient separation method in Group A. The motility values were higher in healthy men than patients with OA before treatment, but there was no improvement in both groups after treatment. CONCLUSIONS: Exogenous administration of MI significantly improves semen's parameters both in patients with OA and in normal fertile men. PMID- 26361941 TI - Lasker Foundation announces award winners for 2015. PMID- 26361942 TI - Global, regional, and national levels and trends in under-5 mortality between 1990 and 2015, with scenario-based projections to 2030: a systematic analysis by the UN Inter-agency Group for Child Mortality Estimation. AB - BACKGROUND: In 2000, world leaders agreed on the Millennium Development Goals (MDGs). MDG 4 called for a two-thirds reduction in the under-5 mortality rate between 1990 and 2015. We aimed to estimate levels and trends in under-5 mortality for 195 countries from 1990 to 2015 to assess MDG 4 achievement and then intended to project how various post-2015 targets and observed rates of change will affect the burden of under-5 deaths from 2016 to 2030. METHODS: We updated the UN Inter-agency Group for Child Mortality Estimation (UN IGME) database with 5700 country-year datapoints. As of July, 2015, the database contains about 17 000 country-year datapoints for mortality of children younger than 5 years for 195 countries, and includes all available nationally representative data from vital registration systems, population censuses, household surveys, and sample registration systems. We used these data to generate estimates, with uncertainty intervals, of under-5 (age 0-4 years) mortality using a Bayesian B-spline bias-reduction model (B3 model). This model includes a data model to adjust for systematic biases associated with different types of data sources. To provide insights into the global and regional burden of under-5 deaths associated with post-2015 targets, we constructed five scenario based projections for under-5 mortality from 2016 to 2030 and estimated national, regional, and global under-5 mortality rates up to 2030 for each scenario. RESULTS: The global under-5 mortality rate has fallen from 90.6 deaths per 1000 livebirths (90% uncertainty interval 89.3-92.2) in 1990 to 42.5 (40.9-45.6) in 2015. During the same period, the annual number of under-5 deaths worldwide dropped from 12.7 million (12.6 million-13.0 million) to 5.9 million (5.7 million 6.4 million). The global under-5 mortality rate reduced by 53% (50-55%) in the past 25 years and therefore missed the MDG 4 target. Based on point estimates, two regions-east Asia and the Pacific, and Latin America and the Caribbean achieved the MDG 4 target. 62 countries achieved the MDG 4 target, of which 24 were low-income and lower-middle income countries. Between 2016 and 2030, 94.4 million children are projected to die before the age of 5 years if the 2015 mortality rate remains constant in each country, and 68.8 million would die if each country continues to reduce its mortality rate at the pace estimated from 2000 to 2015. If all countries achieve the Sustainable Development Goal of an under-5 mortality rate of 25 or fewer deaths per 1000 livebirths by 2030, we project 56.0 million deaths by 2030. About two-thirds of all sub-Saharan African countries need to accelerate progress to achieve this target. INTERPRETATION: Despite substantial progress in reducing child mortality, concerted efforts remain necessary to avoid preventable under-5 deaths in the coming years and to accelerate progress in improving child survival further. Urgent actions are needed most in the regions and countries with high under-5 mortality rates, particularly those in sub-Saharan Africa and south Asia. FUNDING: None. PMID- 26361943 TI - Child survival in 2015: much accomplished, but more to do. PMID- 26361944 TI - Validation and relevance of Rheumatoid Arthritis Pain Scale (RAPS) in Indian (Asian) patients suffering from rheumatoid arthritis. AB - Pain in RA is multifaceted and complex. Measuring instruments are inadequate. Rheumatoid Arthritis Pain Scale (RAPS) (Arthritis Care Res 45:317-323, 2001) was designed to measure pain comprehensively but has been sparsely reported. We decided to validate a suitable version for our community. Post translation (contextual), RAPS was administered (face to face interview) to 172 consenting patients of moderately severe RA (mean pain visual analogue scale (VAS) 5.4 cm) in a cross-sectional study using standard rheumatology case record form. RAPS contained 24 questions (numeric score, anchored at 0 (never) and 6 (always); range 0-144). Fifty-seven cohort patients on supervised rheumatology care were followed for 16 weeks. SPSS (v16) was used for statistical analysis, significant p < 0.05. RAPS showed good face and content validity (consensus). Construct/criterion validity was demonstrated for subclass domains and total RAPS (Cronbach's alpha 0.91, test-retest interclass correlation (Pearson) 0.71). Fair to modest correlation (p < 0.05) was seen with swollen joint count (0.16), Indian health assessment questionnaire (0.23), medical outcome short form (SF), 36 physical score (-0.35), SF 36 mental score (-0.21) and C-reactive protein (0.25), not with pain VAS. Similar results were shown for subclass domains (physiologic, affective, sensory, cognitive), except low alpha for affective. Age, disease duration and SF 36 were significant predictors (linear regression). In factor analysis, RAPS loaded with SF 36. The standardized response mean (0.6) was equal to pain VAS and DAS 28. RAPS was found to be a valid and clinically relevant instrument for measuring pain in Indian patients suffering from RA. It merits more widespread clinical use. PMID- 26361945 TI - Viral RNA in the influenza vaccine may have contributed to the development of ANCA-associated vasculitis in a patient following immunisation. AB - A number of large studies have demonstrated influenza vaccinations to be safe and effective. However, there have been some sporadic case reports, describing a temporal association of influenza vaccination with onset or relapse of anti neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. The nature of this association, beyond time of occurrence, remains unknown. The presentation of a previously healthy patient who developed ANCA-associated vasculitis (AAV) shortly after influenza vaccination provided us with the rare opportunity to study the possible mechanisms behind this observation. We tested the ability of different types and batches of influenza vaccines to stimulate proteinase-3 ANCA (PR3-ANCA) production in vitro. We found that only some influenza vaccines stimulated PR3 ANCA production in this patient. We demonstrated that this unusual response was associated with those vaccines that contained viral ribonucleic acid (RNA), the natural ligand for Toll-like receptor-7. Exome sequencing of the patient's DNA did not show any mutation in any of the molecules associated with Toll-like receptor signalling. We propose that hyper-reaction to viral RNA in the influenza vaccine may have contributed to the development of AAV following influenza vaccination in this patient. PMID- 26361946 TI - Involvement of Kallikrein-Kinin System on Cardiopulmonary Alterations and Inflammatory Response Induced by Purified Aah I Toxin from Scorpion Venom. AB - Bradykinins are released from kininogen by kallikrein. They increase capillary lung permeability after their binding to beta1 and especially beta2 receptors before being metabolized by kininase enzyme. This study was performed to evaluate cardiopulmonary damages and inflammatory response on injected rats with Aah I toxin of scorpion venom and the involvement of Kallikrein-Kinin system in this pathogenesis. Obtained results revealed that Aah I toxin induces inflammatory cell infiltration accompanied by cellular peroxidase activities, a release of cytokine levels, pulmonary and myocardial damage, with altered metabolic activities and imbalanced redox status. Administration of aprotinin (bradykinin inhibitor) and especially icatibant (bradykinin beta2 receptor antagonist) seemed to be able to protect animals against the toxicity of Aah I; nevertheless, the use of captopril (kininase II inhibitor) reduced partially some cardiac disorders. These findings indicate that the kallikrein-kinin system may contribute to the physiopathological effect and lung edema formation induced by toxin, which suggests a potential use of drugs with significant anti-kinin properties. PMID- 26361948 TI - Differential sclerostin and parathyroid hormone response to exercise in boys and men. AB - SUMMARY: Physical exercise benefits bone structure and mineralization, especially in children. Immediately following high-impact exercise, PTH increased and returned to resting values within 24 h in both groups, while sclerostin increased in men but not in boys. The underlying mechanisms and implication of this age related differential response are unclear. INTRODUCTION: Circulating sclerostin, a negative regulator of bone, decreases during puberty and increases in adulthood. Parathyroid hormone (PTH) is inversely related to sclerostin. In mice, sclerostin decreases following 24 h of mechanical stimulation. Its response to exercise in humans and, especially in children, in whom high-impact physical exercise benefits bone structure and mineralization is unclear. The aim of this study was to investigate the acute response of sclerostin to a single exercise session of high mechanical loading and the corresponding changes in PTH in boys and men. METHODS: Twelve boys (10.2 +/- 0.4 years old) and 17 young men (22.7 +/- 0.8 years old) underwent a protocol of plyometric exercises (total 144 jumps). Blood samples were collected pre-, 5 min, 1 h, and 24 h post-exercise. RESULTS: Boys had significantly higher resting values of sclerostin compared with men (150 +/- 37 vs. 111 +/- 34 pg/ml, respectively, p = 0.006). Following exercise, sclerostin markedly increased in men but this response was attenuated in boys (at 5 min: 51 +/- 38 vs. 14 +/- 21%, respectively, p = 0.005). PTH levels were similar in boys and men at rest and throughout the 24-h study period, increasing significantly (p < 0.001) 5 min after exercise, decreasing after 60 min post exercise and returning to resting values within 24 h. CONCLUSION: Although the PTH response was similar in boys and men, the sclerostin response was greater in men. The combined increases in PTH and sclerostin immediately post-exercise appear contrary to the accepted osteogenic effect of exercise. The underlying mechanisms and full implication of the differential response between children and adults need to be further examined. PMID- 26361949 TI - Cryopreserved amniotic membrane as transplant allograft: viability and post transplant outcome. AB - Amniotic membrane (AM) transplantation is increasingly used in ophthalmological and dermatological surgeries to promote re-epithelialization and wound healing. Biologically active cells in the epithelial and stromal layers deliver growth factors and cytokines with anti-inflammatory, anti-bacterial, anti-immunogenic and anti-fibrotic properties. In this work, confocal microscopy was used to show that our cryopreservation protocol for AM yielded viable cells in both the stromal and epithelial layers with favorable post-transplant outcome. AM was obtained from Caesarean-section placenta, processed into allograft pieces of different sizes (3 cm * 3 cm, 5 cm * 5 cm, and 10 cm * 10 cm) and cryopreserved in 10 % dimethyl sulfoxide using non-linear controlled rate freezing. Post-thaw cell viability in the entire piece of AM and in the stromal and epithelial cell layers was assessed using a dual fluorescent nuclear dye and compared to hypothermically stored AM, while surveys from surgical end-users provided information on post-transplant patient outcomes. There was no significant statistical difference in the cell viability in the entire piece, epithelial and stromal layers regardless of the size of allograft piece (p = 0.092, 0.188 and 0.581, respectively), and in the entire piece and stromal layer of hypothermically stored versus cryopreserved AM (p = 0.054 and 0.646, respectively). Surgical end-user feedback (n = 49) indicated that 16.3 % of AM allografts were excellent and 61.2 % were satisfactory. These results support the expanded clinical use of different sizes of cryopreserved AM allografts and address the issue of orientation of the AM during transplant for the treatment of dermatological defects and ocular surface disorders. PMID- 26361950 TI - A coincidence or a rare occurrence? A case of plasmablastic lymphoma of the small intestines following infliximab treatment for Crohn's disease. PMID- 26361952 TI - Rotten context: the unaffordability of technological advances. PMID- 26361947 TI - A biomechanical sorting of clinical risk factors affecting osteoporotic hip fracture. AB - Osteoporotic fracture has been found associated with many clinical risk factors, and the associations have been explored dominantly by evidence-based and case control approaches. The major challenges emerging from the studies are the large number of the risk factors, the difficulty in quantification, the incomplete list, and the interdependence of the risk factors. A biomechanical sorting of the risk factors may shed lights on resolving the above issues. Based on the definition of load-strength ratio (LSR), we first identified the four biomechanical variables determining fracture risk, i.e., the risk of fall, impact force, bone quality, and bone geometry. Then, we explored the links between the FRAX clinical risk factors and the biomechanical variables by looking for evidences in the literature. To accurately assess fracture risk, none of the four biomechanical variables can be ignored and their values must be subject-specific. A clinical risk factor contributes to osteoporotic fracture by affecting one or more of the biomechanical variables. A biomechanical variable represents the integral effect from all the clinical risk factors linked to the variable. The clinical risk factors in FRAX mostly stand for bone quality. The other three biomechanical variables are not adequately represented by the clinical risk factors. From the biomechanical viewpoint, most clinical risk factors are interdependent to each other as they affect the same biomechanical variable(s). As biomechanical variables must be expressed in numbers before their use in calculating LSR, the numerical value of a biomechanical variable can be used as a gauge of the linked clinical risk factors to measure their integral effect on fracture risk, which may be more efficient than to study each individual risk factor. PMID- 26361954 TI - Accessory Soleus: A Case Report of Exertional Compartment and Tarsal Tunnel Syndrome Associated With an Accessory Soleus Muscle. AB - An accessory soleus muscle is a rare anatomic variant that frequently presents as an asymptomatic soft tissue swelling in the posteromedial ankle. Less frequently, the anomalous muscle can cause pain and swelling with activity. We present the case of a 17-year-old male with exertional compartment syndrome and associated tarsal tunnel syndrome secondary to a very large accessory soleus muscle. After surgical excision, the patient was able to return to full activity with complete resolution of symptoms. PMID- 26361953 TI - Antioxidant Effect of Nanoemulsions Containing Extract of Achyrocline satureioides (Lam) D.C.-Asteraceae. AB - Ethanolic extracts of Achyrocline satureioides have pronounced antioxidant activity mainly due to the presence of the flavonoid quercetin. However, direct topical application of the extract is not possible due to the presence of high amounts of ethanol. In this sense, nanoemulsions arise as an alternative for topical formulation associating molecules with limited aqueous solubility. This article describes the development of topical nanoemulsions containing either A. satureioides extract or one of its most abundant flavonoid, quercetin. Nanoemulsions composed of octyldodecanol, egg lecithin, water and extract (NEE), or quercetin (NEQ) were prepared by spontaneous emulsification. This process led to monodisperse nanoemulsions presenting a mean droplet size of approximately 200 300 nm, negative zeta potential, and high association efficiency. A study of quercetin skin retention using porcine skin which was performed using a Franz diffusion cell revealed a higher accumulation of quercetin in skin for NEE when compared to NEQ. Finally, the antioxidant activity of formulations was measured by thiobarbituric acid-reactive species and the APPH model. A lower lipoperoxidation for the extract in respect to quercetin solution was observed. However, no difference between NEQ and NEE lipoperoxidation could be seen. The protection against lipoperoxidation by the formulations was also measured in the skin, where lower formation of reactive species was observed after treatment with NEE. In conclusion, this study shows the formulation effect on the physicochemical properties of nanoemulsions as well as on the skin retention and antioxidant activity of quercetin. PMID- 26361955 TI - Identification of novel therapeutic target genes in acquired lapatinib-resistant breast cancer by integrative meta-analysis. AB - Acquired resistance to lapatinib is a highly problematic clinical barrier that has to be overcome for a successful cancer treatment. Despite efforts to determine the mechanisms underlying acquired lapatinib resistance (ALR), no definitive genetic factors have been reported to be solely responsible for the acquired resistance in breast cancer. Therefore, we performed a cross-platform meta-analysis of three publically available microarray datasets related to breast cancer with ALR, using the R-based RankProd package. From the meta-analysis, we were able to identify a total of 990 differentially expressed genes (DEGs, 406 upregulated, 584 downregulated) that are potentially associated with ALR. Gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the DEGs showed that "response to organic substance" and "p53 signaling pathway" may be largely involved in ALR process. Of these, many of the top 50 upregulated and downregulated DEGs were found in oncogenesis of various tumors and cancers. For the top 50 DEGs, we constructed the gene coexpression and protein-protein interaction networks from a huge database of well-known molecular interactions. By integrative analysis of two systemic networks, we condensed the total number of DEGs to six common genes (LGALS1, PRSS23, PTRF, FHL2, TOB1, and SOCS2). Furthermore, these genes were confirmed in functional module eigens obtained from the weighted gene correlation network analysis of total DEGs in the microarray datasets ("GSE16179" and "GSE52707"). Our integrative meta-analysis could provide a comprehensive perspective into complex mechanisms underlying ALR in breast cancer and a theoretical support for further chemotherapeutic studies. PMID- 26361956 TI - Diagnostic significance of S100A2 and S100A6 levels in sera of patients with non small cell lung cancer. AB - Biochemical markers play a significant role in the diagnosis of lung cancer. Recent studies have demonstrated a link involving S100 Calcium Binding Proteins (S100A2, S100A6) and non-small cell lung cancer (NSCLC), but the expediency of their serum levels in NSCLC has not been established. In this study, we evaluate the potential of serum S100A2 and S100A6 levels as diagnostic markers for NSCLC. Enzyme-linked immunosorbent assay (ELISA) was performed to detect the levels of S100A2 and S100A6 in 141 NSCLC patients and 150 healthy subjects. Serum levels of the two proteins in patients with NSCLC were higher compared to healthy controls (P = 0.0002 for S100A2 and P < 0.0001 for S100A6). Moreover, the levels of S100A2 and S100A6 were higher in the sera of stage I/II NSCLC patients compared to healthy controls with P = 0.01 and <0.0001, respectively. Receiver operating characteristic (ROC) analysis showed that S100A2 could distinguish NSCLC patients from healthy controls (AUC = 0.646), and S100A6 could also identify NSCLC (AUC = 0.668). Meanwhile, these two proteins showed notable capabilities for distinguishing stage I/II NSCLC from healthy controls (AUC = 0.708 for S100A2 and AUC = 0.702 for S100A6). Our results indicate that serum levels of S100A2 and S100A6 are significantly elevated in early stage NSCLC and may have the potential for NSCLC biomarker. Further studies with large sample population would help validate our findings. PMID- 26361958 TI - Identification of expression quantitative trait loci of RPTOR for susceptibility to glioma. AB - Expression quantitative trait loci (eQTLs) have been recognized to be more likely to associate with complex diseases including cancer. As an essential scaffold for MTOR complex 1, RPTOR is necessary for the MTOR-catalyzed phosphorylation. This study examined the associations between the eQTLs of RPTOR and glioma susceptibility. The eQTLs of RPTOR were obtained from GTEx eQTL Browser. Associations were estimated by logistic regression models. On the basis of analysis of 138 cases with glioma and 327 cancer-free population controls, we demonstrated that the eQTL of RPTOR, rs7502563, was significantly associated with a decreased glioma risk [odds ratio (OR) = 0.59, 95 % confidence interval (CI) = 0.38-0.89, P = 0.0123] in a dominant manner. Stratified analyses indicated that the association between rs7502563 and glioma was more pronounced in females (OR = 0.40, 95 % CI = 0.20-0.80, P = 0.0091), older subjects (OR = 0.47, 95 % CI = 0.26 0.86, P = 0.0135), and subjects with high-grade glioma (OR = 0.45, 95 % CI = 0.27 0.77, P = 0.0031). Moreover, an interest gradual decrease in OR with higher grade glioma was observed. Further analysis of the extracted data from GTEx eQTL Browser found that rs7502563 G allele was associated with significantly higher expression of RPTOR in all HapMap populations. Our results demonstrate for the first time that the eQTL of RPTOR, rs7502563, is susceptible to glioma. PMID- 26361957 TI - Prognostic value of several biomarkers for the patients with malignant pleural mesothelioma. AB - Malignant pleural mesothelioma (MPM) is a highly aggressive tumor of the pleura closely related to asbestos exposure. Rare as it is, the incidence of MPM is predicted to increase mainly as a result of a lengthy latency period from the initial asbestos exposure, making it a public health concern for the next decades. Moreover, the patients with MPM have an extremely poor prognosis due to its high resistance to conventional oncologic treatments and delayed diagnosis. Although the result of current therapeutic modalities based on patient features and clinical stages is very frustrating, great advances have been shown in the knowledge of molecular biology of MPM in recent years. This is accompanied by dozens of putative prognostic biomarkers that are actively involved in tumor biological activities. These prognostic candidates can offer us a new insight into the biological characteristics of MPM, contributing to development of individualized therapeutic strategies directed against oncogenesis and tumor progression. Thus, personalized approaches based on the molecular biology of the patient's tissue or body fluid will potentially improve the present disappointing outcome, bringing new hope for patients with MPM. This article reviews the principal and several novel biomarkers that can have an influence on prognosis, in the hope that they can provide us with a more profound understanding of the biology of this lethal disease. PMID- 26361959 TI - Regulation of beta-catenin transcription activity by leupaxin in hepatocellular carcinoma. AB - In human cancers, beta-catenin is accumulated in the nucleus and activates mRNA transcription of many oncogenic genes, such as cyclin D1 and c-myc. However, the mechanism of beta-catenin-mediated transcriptional activation remains largely unknown. In the present study, we identified leupaxin, an adaptor protein sharing homology with the focal adhesion protein, as a novel coactivator for beta-catenin in human hepatocellular carcinoma (HCC). We show that leupaxin could interact with beta-catenin and enhance its transcriptional activity through recruitment of coactivator complex, including steroid receptor coactivator 1 (SRC-1) and P300. As a result, leupaxin regulates HCC cell proliferation and cell-cycle progression in the presence of intact Wnt/beta-catenin signaling. Furthermore, leupaxin is overexpressed in HCC tissues and correlated with mRNA levels of cyclin D1 and c myc. Therefore, this is the first demonstration of a role for the leupaxin in the regulation of HCC progression, at least in part, by enhancing beta-catenin transcription activity. PMID- 26361960 TI - Evaluation of lamina cribrosa thickness and depth in ocular hypertension. AB - PURPOSE: To investigate the differences in thickness and depth of the lamina cribrosa (LC) between ocular hypertension (OH) patients and normal control subjects, using enhanced depth imaging (EDI) spectral-domain optical coherence tomography (SD-OCT). METHODS: EDI-OCT data were obtained from the subjects in a cross-sectional analysis of data from a retrospective study. After IOP correction according to central corneal thickness (CCT), we divided the OH patients into two groups based on the corrected IOP (cIOP)--OH with lower IOP (OH-L; cIOP < 23 mmHg) and OH with higher IOP (OH-H; cIOP >= 23 mmHg). Comparisons of LC thickness and depth among three groups were performed. RESULTS: Seventy-four OH patients and 45 normal control subjects were included in the analysis. Among the 74 OH patients, 41 were included in the OH-L group and 33 were included in the OH-H group. LC thickness was thicker in the OH-H group compared to normal controls both in superior (P = 0.02) and inferior (P = 0.01) portions. However, no difference was found in LC depth among the three groups in any portion (P = 0.36; P = 0.44; P = 0.31, respectively). CONCLUSION: OH patients may have a thicker LC than normal control subjects, especially in OH with definite high IOP. PMID- 26361961 TI - Antipsychotic medications and extreme weight gain in two health systems. AB - OBJECTIVE: We conducted this study to investigate the rate of clinically important, extreme weight gain (EWG; >=7% body weight gain) among all second generation antipsychotic (SGA) users in two large health care systems in the United States. STUDY DESIGN: Retrospective observational cohort study. METHODS: We used electronic medical record databases of two health systems to identify adults aged 18-79 years who from 1 January 2004 to 31 December 2011 had initiated a SGA medication. All patients had to have a minimum of two weight measures in the medical record: (1) one or more weights in the 180-day pre-treatment (baseline) period; and (2) one or more weights in the first year after initiating SGA treatment. RESULTS: We found that EWG occurred in 7.7-17.0% of SGA users. At one year, the average weight gain was nearly 10kg among SGA users who experienced EWG. Olanzapine was the SGA most commonly associated with EWG with a rate of 17.0 per 100 users [95% confidence interval (CI): 14.2-20.5], while ziprasidone was least commonly associated with EWG (7.7 per 100 users; 95% CI: 4.6-13.0). CONCLUSIONS: We found that clinically-important weight gain was common after the initiation of SGA treatment, and the EWG phenotype was easily identifiable within electronic medical records. There was significant heterogeneity in the rate of EWG across SGA medications. Weight gains of this magnitude are likely to have adverse health consequences and there is a significant unmet opportunity for physicians to identify these events and mitigate the harms of SGA use. PMID- 26361962 TI - Mouse model of proximal colon-specific tumorigenesis driven by microsatellite instability-induced Cre-mediated inactivation of Apc and activation of Kras. AB - BACKGROUND: KRAS gene mutations are found in 40-50% of colorectal cancer cases, but their functional contribution is not fully understood. To address this issue, we generated genetically engineered mice with colon tumors expressing an oncogenic Kras(G12D) allele in the context of the Adenomatous polyposis coli (Apc) deficiency to compare them to tumors harboring Apc deficiency alone. METHODS: CDX2P9.5-G22Cre (referred to as G22Cre) mice showing inducible Cre recombinase transgene expression in the proximal colon controlled under the CDX2 gene promoter were intercrossed with Apc (flox/flox) mice and LSL-Kras (G12D) mice carrying loxP-flanked Apc and Lox-Stop-Lox oncogenic Kras(G12D) alleles, respectively, to generate G22Cre; Apc(flox/flox); Kras(G12D) and G22Cre; Apc(flox/flox); KrasWT mice. Gene expression profiles of the tumors were analyzed using high-density oligonucleotide arrays. RESULTS: Morphologically, minimal difference in proximal colon tumor was observed between the two mouse models. Consistent with previous findings in vitro, Glut1 transcript and protein expression was up-regulated in the tumors of G22Cre;Apc (flox/flox) ; Kras(G12D) mice. Immunohistochemical staining analysis revealed that GLUT1 protein expression correlated with KRAS mutations in human colorectal cancer. Microarray analysis identified 11 candidate genes upregulated more than fivefold and quantitative PCR analysis confirmed that Aqp8, Ttr, Qpct, and Slc26a3 genes were upregulated 3.7- to 30.2-fold in tumors with mutant Kras. CONCLUSIONS: These results demonstrated the validity of the G22Cre; Apc(flox/flox) ;Kras (G12D) mice as a new mouse model with oncogenic Kras activation. We believe that this model can facilitate efforts to define novel factors that contribute to the pathogenesis of human colorectal cancer with KRAS mutations. PMID- 26361963 TI - Cardiovascular risk models for South Asian populations: a systematic review. AB - OBJECTIVES: To review existing cardiovascular risk models applicable to South Asian populations. METHODS: A systematic review of the literature using a combination of search terms for "South Asian", "cardiovascular", "risk"/"score" and existing risk models for inclusion. South Asian was defined as those residing in or with ancestry belonging to the Indian subcontinent. RESULTS: The literature search including MEDLINE and EMBASE identified 7560 papers. After full-text review, 4 papers met the inclusion criteria. Only 1 reported formal measures of model performance. In that study, both a modified Framingham model and QRISK2 showed similar good discrimination with AUROCs of 0.73-0.77 with calibration also reasonable in men (0.71-0.93) but poor in women (0.43-0.52). CONCLUSIONS: Considering the number of South Asians and prevalence of cardiovascular disease, very few studies have reported performance of risk scores in South Asian populations. Furthermore, it was difficult to make comparisons, as many did not provide measures of discrimination, accuracy and calibration. There is a need for further research to evaluate risk models in South Asians, and ideally derive and validate cardiovascular risk models within South Asian populations. PMID- 26361964 TI - Understanding Seniors' Choices in Medicare Advantage. PMID- 26361966 TI - Schmallenberg virus infection in South American camelids: Field and experimental investigations. AB - During the first epizootic wave of the novel, teratogenic Schmallenberg virus (SBV, Orthobunyavirus) in ruminants in Northern Europe, serological evidence of a previous SBV-infection demonstrated that South American camelids (SAC) are also susceptible to SBV. However, their potential role in SBV spread remains unknown. To investigate the prevalence and course of SBV-infection in SAC, a German field study and an animal trial with three llamas and three alpacas were conducted. From September 2012 to December 2013, 313 of 502 SAC (62.35%) were found SBV seropositive, but negative for SBV-RNA. The estimated between-district (94.23% of 52) and median within-district (71.43%) and herd (73.13%) SBV seroprevalence in German SAC was similar to the seroprevalence reported in cattle herds and sheep flocks at the time. An age of >1 year was found a statistically significant risk factor for SBV-infection, which could be explained by the spatio-temporal spread of SBV in Germany during the study period. No clinical signs or an increase of abortion and congenital malformation associated with SBV-infection in SAC were reported by the study participants. Similar to SBV-infected ruminants, SBV RNAemia in experimentally SBV-infected SAC was detected for a short time between days 3 and 7 after infection (dpi), and seroconversion occurred between 9 and 21 dpi. Despite the similar virological and serological results, the lack of clinical signs and congenital malformation associated with SBV-infection suggests that SBV causes subclinical infection in SAC. However, their role as reservoirs in the spread of SBV has to be further investigated. PMID- 26361965 TI - Health Conditions and Functional Status in Adults with Autism: A Cross-Sectional Evaluation. AB - BACKGROUND: Children and adolescents with autism spectrum disorder (ASD) have many well-known health concerns, yet health conditions in adults with ASD remain poorly defined. OBJECTIVE: To examine health conditions and functional status in adults with ASD and identify factors associated with health and functional status across age cohorts. DESIGN AND SUBJECTS: We collected cross-sectional data from 255 adult subjects aged 18 to 71 years with ASD using the Rochester Health Status Survey IV (RHSS-IV), a 58-item validated survey instrument. We used the National Health and Nutritional Examination Survey and National Health Interview Survey to provide comparative prevalence rates in the general population. RESULTS: Compared to the general population, young adults aged 18-29 with ASD had a substantially higher prevalence of seizure disorder (11.2 % vs. 1.4 %; p = 0.002), depression (16.4 % vs. 6.4 %; p = 0.007), hypertension (12.9 % vs. 6.3 %; p = 0.05), and allergies (39.7 % vs. 8.4 %; p < 0.001). In contrast, young adults with ASD had considerably lower rates of sexually transmitted illness (STI) (0.9 % vs. 4.3 %; p = 0.03), tobacco use (5.2 % vs. 31.9 %; p < 0.001), and alcohol misuse (0.9 % vs. 11.9 %; p < 0.001). Adults 40 and over with ASD also had higher rates of seizure disorder (29.2 % vs. 1.7 %; p < 0.001), lower tobacco use (2.8 % vs. 24.5 %; p < 0.001), and lower alcohol misuse (1.4 % vs. 18.2 %; p < 0.001) compared to the general population. Amongst the 55 % of participants with a documented IQ score, 91 % had an intellectual disability (IQ < 70). Within the cohort aged 40 years old and older, only 54.2 % were independent with eating, 43.0 % independent with dressing, and 43.1 % independent with bathing. Lower IQ and depression were associated with lower functional status. CONCLUSIONS: Adults with ASD have a high prevalence of seizure disorders and depression, but low rates of STIs, tobacco use, and alcohol misuse. Within our cohort, the majority of older adults with ASD required some assistance with activities of daily living. PMID- 26361967 TI - Effect of Silicon Supplementation on Bone Status in Ovariectomized Rats Under Calcium-Replete Condition. AB - Previous studies have suggested that silicon (Si) had positive effects on bone, but such benefits from Si may be dependent on calcium status. Also, several biochemical roles of Si in osteoblastic mineralization, the regulation of gene expression related to bone matrix synthesis, and the decrease in reactive oxygen species and pro-inflammatory mediators were reported, but these effects were mostly shown in cell culture studies. Hence, we tested the effect of Si supplementation on bone status and the gene expression related to bone metabolism and inflammatory mediators in young estrogen-deficient rats under calcium-replete condition (0.5 % diet). Results showed that 15-week supplementation of both high and very high doses of Si (0.025 and 0.075 % diet, respectively) could not restore the ovariectomy (OVX)-induced decrease of bone mineral density (BMD) of vertebrae, femur, and tibia. Also, several bone biochemical markers (ALP, osteocalcin, CTx) and mRNA expression of COL-I, RANKL, IL-6, and TNF-alpha in femur metaphysis were not significantly changed by Si in OVX rats. However, a very high dose (0.075 %) of Si supplementation significantly increased OPG expression and decreased the ratio of RANKL/OPG in mRNA expression comparable to that of sham-control animals. Taken together, Si supplementation did not increase BMD under calcium-replete condition but the decrease in the ratio of RANKL/OPG expression to the normal level suggests the possibility of a bone health benefit of Si in estrogen deficiency-induced bone loss. PMID- 26361968 TI - Up-regulation of activating and inhibitory NKG2 receptors in allogeneic and autologous hematopoietic stem cell grafts. AB - BACKGROUND: Hematopoietic Stem Cell Transplantation (HSCT) is known to induce the inhibitory immune receptor NKG2A on NK cells of donor origin. This occurs in allogeneic recipients, in both the haploidentical and HLA-matched settings. METHODS: To gain further insight, not only NKG2A, but also the activating receptors NKG2C and NKG2D were assessed by flow cytometry. Immunophenotyping was carried out not only on CD56(+) but also on CD8(+) lymphocytes from leukemia and lymphoma patients, receiving both HLA-matched (n = 7) and autologous (n = 5) HSCT grafts. Moreover, cognate NKG2 ligands (HLA-E, MICA, ULBP-1, ULBP-2 and ULBP-3) were assessed by immunohistochemistry in diagnostic biopsies from three autotransplanted patients, and at relapse in one case. RESULTS: All the NKG2 receptors were simultaneously up-regulated in all the allotransplanted patients on CD8(+) and/or CD56(+) cells between 30 and 90 days post-transplant, coinciding with, or following, allogeneic engraftment. Up-regulation was of lesser entity and restricted to CD8(+) cells in the autotransplantation setting. The phenotypic expression ratio between activating and inhibitory NKG2 receptors was remarkably similar in all the patients, except two outliers (a long survivor and a short survivor) who surprisingly displayed a similar NKG2 activation immunophenotype. Tumor expression of 2 to 3 out of the 5 tested NKG2 ligands was observed in 3/3 diagnostic biopsies, and 3 ligands were up-regulated post-transplant in a patient. CONCLUSIONS: Altogether, these results are consistent with a dual (activation-inhibition) NK cell re-education mode, an innate-like T cell re tuning, and a ligand:receptor interplay between the tumor and the immune system following HSCT including, most interestingly, the up-regulation of several activating NKG2 ligands. Turning the immune receptor balance toward activation on both T and NK cells of donor origin may complement ex vivo NK cell expansion/activation strategies in unmanipulated patients. PMID- 26361970 TI - Maintenance therapy for metastatic colorectal cancer. PMID- 26361969 TI - Adjuvant sorafenib for hepatocellular carcinoma after resection or ablation (STORM): a phase 3, randomised, double-blind, placebo-controlled trial. AB - BACKGROUND: There is no standard of care for adjuvant therapy for patients with hepatocellular carcinoma. This trial was designed to assess the efficacy and safety of sorafenib versus placebo as adjuvant therapy in patients with hepatocellular carcinoma after surgical resection or local ablation. METHODS: We undertook this phase 3, double-blind, placebo-controlled study of patients with hepatocellular carcinoma with a complete radiological response after surgical resection (n=900) or local ablation (n=214) in 202 sites (hospitals and research centres) in 28 countries. Patients were randomly assigned (1:1) to receive 400 mg oral sorafenib or placebo twice a day, for a maximum of 4 years, according to a block randomisation scheme (block size of four) using an interactive voice response system. Patients were stratified by curative treatment, geography, Child Pugh status, and recurrence risk. The primary outcome was recurrence-free survival assessed after database cut-off on Nov 29, 2013. We analysed efficacy in the intention-to-treat population and safety in randomly assigned patients receiving at least one study dose. The final analysis is reported. This study is registered with ClinicalTrials.gov, number NCT00692770. FINDINGS: We screened 1602 patients between Aug 15, 2008, and Nov 17, 2010, and randomly assigned 1114 patients. Of 556 patients in the sorafenib group, 553 (>99%) received the study treatment and 471 (85%) terminated treatment. Of 558 patients in the placebo group, 554 (99%) received the study treatment and 447 (80%) terminated treatment. Median duration of treatment and mean daily dose were 12.5 months (IQR 2.6-35.8) and 577 mg per day (SD 212.8) for sorafenib, compared with 22.2 months (8.1-38.8) and 778.0 mg per day (79.8) for placebo. Dose modification was reported for 497 (89%) of 559 patients in the sorafenib group and 206 (38%) of 548 patients in the placebo group. At final analysis, 464 recurrence-free survival events had occurred (270 in the placebo group and 194 in the sorafenib group). Median follow up for recurrence-free survival was 8.5 months (IQR 2.9-19.5) in the sorafenib group and 8.4 months (2.9-19.8) in the placebo group. We noted no difference in median recurrence-free survival between the two groups (33.3 months in the sorafenib group vs 33.7 months in the placebo group; hazard ratio [HR] 0.940; 95% CI 0.780-1.134; one-sided p=0.26). The most common grade 3 or 4 adverse events were hand-foot skin reaction (154 [28%] of 559 patients in the sorafenib group vs four [<1%] of 548 patients in the placebo group) and diarrhoea (36 [6%] vs five [<1%] in the placebo group). Sorafenib-related serious adverse events included hand-foot skin reaction (ten [2%]), abnormal hepatic function (four [<1%]), and fatigue (three [<1%]). There were four (<1%) drug-related deaths in the sorafenib group and two (<1%) in the placebo group. INTERPRETATION: Our data indicate that sorafenib is not an effective intervention in the adjuvant setting for hepatocellular carcinoma following resection or ablation. PMID- 26361971 TI - Maintenance strategies after first-line oxaliplatin plus fluoropyrimidine plus bevacizumab for patients with metastatic colorectal cancer (AIO 0207): a randomised, non-inferiority, open-label, phase 3 trial. AB - BACKGROUND: The definition of a best maintenance strategy following combination chemotherapy plus bevacizumab in metastatic colorectal cancer is unclear. We investigated whether no continuation of therapy or bevacizumab alone are non inferior to fluoropyrimidine plus bevacizumab, following induction treatment with a fluoropyrimidine plus oxaliplatin plus bevacizumab. METHODS: In this open label, non-inferiority, randomised phase 3 trial, we included patients aged 18 years or older with histologically confirmed, previously untreated metastatic colorectal cancer, Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, adequate bone marrow, liver, and renal function, no pre-existing neuropathy greater than grade 1, and measurable disease, from 55 hospitals and 51 private practices in Germany. After 24 weeks of induction therapy with either fluorouracil plus leucovorin plus oxaliplatin or capecitabine plus oxaliplatin, both with bevacizumab, patients without disease progression were randomly assigned centrally by fax (1:1:1) to standard maintenance treatment with a fluoropyrimidine plus bevacizumab, bevacizumab alone, or no treatment. Both patients and investigators were aware of treatment assignment. Stratification criteria were response status, termination of oxaliplatin, previous adjuvant treatment with oxaliplatin, and ECOG performance status. At first progression, re induction with all drugs of the induction treatment was a planned part of the protocol. Time to failure of strategy was the primary endpoint, defined as time from randomisation to second progression after maintenance (and if applicable re induction), death, or initiation of further treatment including a new drug. Time to failure of strategy was equivalent to time to first progression for patients who did not receive re-induction (for any reason). The boundary for assessment of non-inferiority was upper limit of the one-sided 98.8% CI 1.43. Analyses were done by intention to treat. The study has completed recruitment, but follow-up of participants is ongoing. The trial is registered with ClinicalTrials.gov, number NCT00973609. FINDINGS: Between Sept 17, 2009, and Feb 21, 2013, 837 patients were enrolled and 472 randomised; 158 were randomly assigned to receive fluoropyrimidine plus bevacizumab, 156 to receive bevacizumab monotherapy, and 158 to receive no treatment. Median follow-up from randomisation is 17.0 months (IQR 9.5-25.4). Median time to failure of strategy was 6.9 months (95% CI 6.1 8.5) for the fluoropyrimidine plus bevacizumab group, 6.1 months (5.3-7.4) for the bevacizumab alone group, and 6.4 months (4.8-7.6) for the no treatment group. Bevacizumab alone was non-inferior to standard fluoropyrimidine plus bevacizumab (hazard ratio [HR] 1.08 [95% CI 0.85-1.37]; p=0.53; upper limit of the one-sided 99.8% CI 1.42), whereas no treatment was not (HR 1.26 [0.99-1.60]; p=0.056; upper limit of the one-sided 99.8% CI 1.65). The protocol-defined re-induction after first progression was rarely done (30 [19%] patients in the fluoropyrimidine plus bevacizumab group, 67 [43%] in the bevacizumab monotherapy group, and 73 [46%] in the no treatment group. The most common grade 3 adverse event was sensory neuropathy (21 [13%] of 158 patients in the fluoropyrimidine plus bevacizumab group, 22 [14%] of 156 patients in the bevacizumab alone group, and 12 [8%] of 158 patients in the no treatment group). INTERPRETATION: Although non-inferiority for bevacizumab alone was demonstrated for the primary endpoint, maintenance treatment with a fluoropyrimidine plus bevacizumab may be the preferable option for patients following an induction treatment with a fluoropyrimidine, oxaliplatin, and bevacizumab, as it allows the planned discontinuation of the initial combination without compromising time with controlled disease. Only a few patients were exposed to re-induction treatment, thus deeming the primary endpoint time to failure of strategy non-informative and clinically irrelevant. Progression-free survival and overall survival should be considered primary endpoints in future trials exploring maintenance strategies. PMID- 26361973 TI - Secreted lipoxygenase from Pseudomonas aeruginosa exhibits biomembrane oxygenase activity and induces hemolysis in human red blood cells. AB - Pseudomonas aeruginosa (PA) expresses a secreted lipoxygenase (LOX), which oxygenates free arachidonic acid predominantly to 15S-H(p)ETE. The enzyme is capable of binding phospholipids at its active site and physically interacts with model membranes. However, its membrane oxygenase activity has not been quantified. To address this question, we overexpressed PA-LOX as intracellular his-tag fusion protein in Escherichia coli, purified it to electrophoretic homogeneity and compared its biomembrane oxygenase activity with that of rabbit ALOX15. We found that both enzymes were capable of oxygenating mitochondrial membranes to specific oxygenation products and 13S-H(p)ODE and 15S-H(p)ETE esterified to phosphatidylcholine and phosphatidylethanolamine were identified as major oxygenation products. When normalized to similar linoleic acid oxygenase activity, the rabbit enzyme exhibited a much more effective mitochondrial membrane oxygenase activity. In contrast, during long-term incubations (24 h) with red blood cells PA-LOX induced significant (50%) hemolysis whereas rabbit ALOX15 was more or less ineffective. These data indicate the principle capability of PA-LOX of oxygenating membrane bound phospholipids which is likely to alter the barrier function of the biomembranes. Although the membrane oxygenase activity was lower than the fatty acid oxygenase activity of PA-LOX red blood cell membrane oxygenation might be of biological relevance for P. aeruginosa septicemia. PMID- 26361972 TI - Red eyes presenting with a fistulous lesion in the left lower extremity: a case report. AB - INTRODUCTION: Very few cases of scar sarcoidosis affecting the eyes and bone together have been reported in the last few years. CASE PRESENTATION: We report a case of a 49-year-old Spanish man with recurrent bilateral granulomatous uveitis and a fistulous nodular lesion in the left pre-tibial region (scar granuloma) on the site of an 8-year-old scar. He presented with bilateral hilar adenopathies and elevation of inflammatory markers and angiotensin-converting enzyme. A histologically confirmed sarcoid of the tibia with a radiologic appearance unusual for long tubular bone involvement was observed. He also had bilateral ophthalmologic involvement. CONCLUSIONS: Sarcoidosis is a disease of unknown cause histologically characterized by non-caseating granulomas that can involve any organ or tissue. Osseous sarcoidosis is a relatively rare presentation. However, on the basis of cases reported in the literature, sarcoid lesions on bones are generally asymptomatic. Biologic agents are considered an alternative therapy for sarcoidosis resistant to conventional treatment. PMID- 26361974 TI - Kinetic analysis of electron flux in cytochrome P450 reductases reveals differences in rate-determining steps in plant and mammalian enzymes. AB - Herein, we compare the kinetic properties of CPR from Arabidopsis thaliana (ATR2), with CPR from Artemisia annua (aaCPR) and human CPR (hCPR). While all three CPR forms elicit comparable rates for cytochrome c(3+) turnover, NADPH reduction of the FAD cofactor is ~50-fold faster in aaCPR and ATR2 compared to hCPR, with a kobs of ~500 s(-1) (6 degrees C). Stopped-flow analysis of the isolated FAD-domains reveals that NADP(+)-FADH2 charge-transfer complex formation is also significantly faster in the plant enzymes, but the rate of its decay is comparable for all three proteins. In hCPR, transfer of a hydride ion from NADPH to FAD is tightly coupled to subsequent FAD to FMN electron transfer, indicating that the former catalytic event is slow relative to the latter. In contrast, interflavin electron transfer is slower than NADPH hydride transfer in aaCPR and ATR2, occurring with an observed rate constant of ~50 s(-1). Finally, the transfer of electrons from FMN to cytochrome c(3+) is rapid (>10(3) s(-1)) in all three enzymes and does not limit catalytic turnover. In combination, the data reveal differences in rate-determining steps between plant CPR and their mammalian equivalent in mediating the flux of reducing equivalents from NADPH to external electron acceptors. PMID- 26361975 TI - Carotenoid binding to proteins: Modeling pigment transport to lipid membranes. AB - Carotenoid pigments play numerous important physiological functions in human organism. Very special is a role of lutein and zeaxanthin in the retina of an eye and in particular in its central part, the macula lutea. In the retina, carotenoids can be directly present in the lipid phase of the membranes or remain bound to the protein-pigment complexes. In this work we address a problem of binding of carotenoids to proteins and possible role of such structures in pigment transport to lipid membranes. Interaction of three carotenoids, beta carotene, lutein and zeaxanthin with two proteins: bovine serum albumin and glutathione S-transferase (GST) was investigated with application of molecular spectroscopy techniques: UV-Vis absorption, circular dichroism and Fourier transform infrared spectroscopy (FTIR). Interaction of pigment-protein complexes with model lipid bilayers formed with egg yolk phosphatidylcholine was investigated with application of FTIR, Raman imaging of liposomes and electrophysiological technique, in the planar lipid bilayer models. The results show that in all the cases of protein and pigment studied, carotenoids bind to protein and that the complexes formed can interact with membranes. This means that protein-carotenoid complexes are capable of playing physiological role in pigment transport to biomembranes. PMID- 26361977 TI - Effects of social activity on health-related quality of life according to age and gender: an observational study. AB - BACKGROUND: The aim of this study was to examine the relationship between types and amount of social activity and health-related quality of life according to gender and age group. METHODS: This study used data from the Community Health Survey (CHS), which was collected in 2011 and consisted of 229,226 participants aged 19 or older. A linear mixed effects model was used to evaluate the factors influencing health-related quality of life among individuals tracked in the CHS and, in particular, to analyze the associations between the amount and types of social activities participated in and the EuroQol EQ-5D assessment. RESULTS: We found that the average quality of life increased according to the amount of social activities individuals participated in (zero = 89.30, one = 93.28, two = 95.25, three = 96.27, four = 96.85). When people participated in one social activity, social activity was more strongly associated with EQ-5D in the elderly age group (males: 19-34 years = 0.195, 35-49 years = 0.642, 50-64 years = 1.716, >= 65 years = 4.408; females: 19-34 years = 0.170, 35-49 years = 0.502, 50-64 years = 1.411, >= 65 years = 4.180). More participation was positively associated with higher EQ-5D (one = 1.939, two = 2.377, three = 2.439, four = 2.515, p for trend < 0.0001). In females, those who participated in relationship organizations had a higher EQ-5D than those who participated in other types of social activities (Females >= 65 age group; Relationship = 4.373, Leisure = 2.620, Religion = 1.842, Charity = 1.544). CONCLUSION: There was a positive association between the increase in the number of social activities and increase in health related quality of life, especially when evaluated in terms of type of social activities and health-related quality of life according to gender and age group. PMID- 26361976 TI - Reasons for home delivery and use of traditional birth attendants in rural Zambia: a qualitative study. AB - BACKGROUND: Despite the policy change stopping traditional birth attendants (TBAs) from conducting deliveries at home and encouraging all women to give birth at the clinic under skilled care, many women still give birth at home and TBAs are essential providers of obstetric care in rural Zambia. The main reasons for pregnant women's preference for TBAs are not well understood. This qualitative study aimed to identify reasons motivating women to giving birth at home and seek the help of TBAs. This knowledge is important for the design of public health interventions focusing on promoting facility-based skilled birth attendance in Zambia. METHODS: We conducted ten focus group discussions (n = 100) with women of reproductive age (15-45 years) in five health centre catchment areas with the lowest institutional delivery rates in the district. In addition, a total of 30 in-depth interviews were conducted comprising 5 TBAs, 4 headmen, 4 husbands, 4 mothers, 4 neighbourhood health committee (NHC) members, 4 community health workers (CHWs) and 5 nurses. Perspectives on TBAs, the decision-making process regarding home delivery and use of TBAs, and reasons for preference of TBAs and their services were explored. RESULTS: Our findings show that women's lack of decision- making autonomy regarding child birth, dependence on the husband and other family members for the final decision, and various physical and socioeconomic barriers including long distances, lack of money for transport and the requirement to bring baby clothes and food while staying at the clinic, prevented them from delivering at a clinic. In addition, socio-cultural norms regarding childbirth, negative attitude towards the quality of services provided at the clinic, made most women deliver at home. Moreover, most women had a positive attitude towards TBAs and perceived them to be respectful, skilled, friendly, trustworthy, and available when they needed them. CONCLUSION: Our findings suggest a need to empower women with decision-making skills regarding childbirth and to lower barriers that prevent them from going to the health facility in time. There is also need to improve the quality of existing facility based delivery services and to strengthen linkages between TBAs and the formal health system. PMID- 26361979 TI - [Ischemic stroke in the young adult]. AB - Ischemic stroke is not rare in young adults since one in ten stroke patients are less than 50 years old. This incidence increased over the past last years, mainly due to the rise in the prevalence of traditional vascular risk factors in this sub-group of age but also of illegal drug use. Even though both survival and functional outcome of young stroke patients are better than those observed in older patients, socio-economic and quality of life consequences make this disease a main objective in terms of primary and secondary prevention. Identifying the cause of ischemic stroke in young adults is of major importance to prevent stroke recurrence. However, given the wide variety of potential underlying causes, the etiologic work-up of stroke in young adults requires a different approach from that in the elderly. In this context, a sequential diagnostic work-up is needed in order to optimize the yield of diagnostic tests, to reduce their cost and risks for the patient. Arterial dissection is the most frequent cause of stroke in young adults but other less frequent causes are numerous. Despite a comprehensive work-up, about one third of cases remains unexplained leading to the diagnosis of cryptogenic ischemic stroke. PMID- 26361980 TI - Expression of a functional cold active beta-galactosidase from Planococcus sp-L4 in Pichia pastoris. AB - Lactase deficiency problem discourages many adults from consuming milk as a major source of micro- and macronutrients. Enzymatic hydrolysis of lactose is an ideal solution for this problem but such processing adds significant costs. In this study, a cold active beta-galactosidase from Planococcus sp-L4 (bgal) was optimized for expression of recombinant "BGalP" in Pichia pastoris. As a result of codon optimization, the codon adaptation index was improved from 0.58 to 0.85 after replacing rare codons. After transformation of two P. pastoris strains (KM71H and GS115), the activity of BGalP enzyme was measured in the culture supernatants using ortho-Nitrophenyl-beta-galactoside (ONPG). Maximal activity was recorded as 3.7U/ml on day 11 in KM71H clone #2 which was 20% higher than the best GS115 clone. Activity measurements under different conditions indicated optimal activity at pH 6.5. It was active at temperatures ranging from 0 to 55 degrees C with deactivation occurring at or above 60 degrees C. Protein analysis of the crude ultra-filtrate showed the enzyme was ~75kDa and was the major constituent (85%) of the sample. This enzyme have the potential to find utility for the breakdown of lactose in chilled milk and subsequently can be deactivated by pasteurization. The use of BGalP would minimize energy consumption thus decreasing cost and also help to preserve the nutritional elements of the milk. PMID- 26361978 TI - Adherence to drug treatments and adjuvant barrier repair therapies are key factors for clinical improvement in mild to moderate acne: the ACTUO observational prospective multicenter cohort trial in 643 patients. AB - BACKGROUND: In acne, several studies report a poor adherence to treatments. We evaluate, in a real-life setting conditions, the impact of compliance to physician's instructions, recommendations and adherence to the treatments on clinical outcome in patients with mild to moderate acne in an observational, non interventional prospective study carried out in 72 Dermatologic Services in Spain (ACTUO Trial). METHODS: Six-hundred-forty-three subjects were enrolled and 566 patients (88 %) completed the 3 study visits. Study aimed to evaluate the impact of adherence (assessed with ECOB scale) on clinical outcome, as well as how the use of specific adjuvant treatments (facial cleansing, emollient, moisturizing and lenitive specific topical products) influences treatment's adherence and acne severity (0-5 points score). Recommendation of specific adjuvant skin barrier repair products was made in 85.2 %. RESULTS: Overall, clinical improvement was observed throughout follow-up visits with an increased proportion of patients who reported reductions of >=50 % on the total number of lesions (2 months: 25.2 %; 3 months: 57.6 %) and reductions of severity scores (2.5, 2.0 and 1.3 at 1, 2 and 3 months after treatment, respectively). Adherence to treatment was associated with a significant reduction on severity grading, a lower number of lesions and a higher proportion of patients with >=50 % improvement. CONCLUSIONS: Good adherence to medication plus adherence to adjuvants was significantly associated with a higher clinical improvement unlike those that despite adherence with medication had a low adherence to adjuvants. A good adherence to adjuvant treatment was associated with improved adherence and better treatment outcomes in mild to moderate acne patients. (ISRCTN Registry: ISRCTN14257026). PMID- 26361981 TI - Operative risk and preoperative hematocrit in bypass graft surgery: Role of gender and blood transfusion. AB - BACKGROUND: The association between lower preoperative hematocrit (Hct) and risk for morbidity/mortality after cardiac surgery is well established. We examined whether the impact of low preoperative Hct on outcome is modified by blood transfusion and operative risk in women and men undergoing nonemergent CABG surgery. METHODS: Patients having nonemergent, first-time, isolated CABG were included (N=2757). Logistic regressions assessed effect of hematocrit on major perioperative morbidity/mortality separately by males (n=2232) and females (n=525). RESULTS: Mean age was 63.2+/-10.1years, preoperative hematocrit was 38.9+/-4.8%, and STS risk score was 1.3+/-1.8%. Blood transfusion was more likely in female patients (26% vs. 12%, P<0.001). Multivariate analyses revealed that lower body mass index and lower preoperative hematocrit predicted transfusion in males and females, whereas older age (OR=1.03, P=0.017) also predicted transfusion in females. Major morbidity was also more likely in female patients (12% vs. 7%, P<0.001). In multivariate analyses, blood transfusion was the only predictive factor for major morbidity in females (OR=4.56, P<0.001). In males, higher body mass index (OR=1.07, P<0.001), lower hematocrit (OR=0.94, P=0.017), interaction of STS score with hematocrit (OR=1.02, P=0.045), and blood transfusion (OR=9.22, P<0.001) were significant predictors for major morbidity. CONCLUSIONS: This study showed females were more likely to have blood transfusion and major morbidities after nonemergent CABG. Traditional factors that have been found to predict outcomes, such as hematocrit and STS risk, were related only to major morbidity in male patients. However, blood transfusion negatively impacted major outcome after nonemergent CABG surgery across all STS risk levels in both genders. PMID- 26361982 TI - A method for recording facial motor response over occipitalis muscle. PMID- 26361983 TI - Dynamic susceptibility contrast MRI measures of relative cerebral blood volume continue to show promise as an early response marker in the setting of bevacizumab treatment. PMID- 26361984 TI - The 2 + 1 paradigm: an efficient algorithm for central reading of Mayo endoscopic subscores in global multicenter phase 3 ulcerative colitis clinical trials. AB - Despite its importance and potential impact in clinical trials, central reading continues to be an under-represented topic in the literature about inflammatory bowel disease (IBD) clinical trials. Although several IBD studies have incorporated central reading to date, none have fully detailed the specific methodology with which the reads were conducted. Here we outline key principles for designing an efficient central reading paradigm for an ulcerative colitis (UC) study that addresses regulatory, operational and clinical expectations. As a step towards standardization of read methodology for the growing number of multicenter phase 3 clinical trials in IBD, we have applied these principles to the design of an optimal read methodology that we call the '2 + 1 paradigm.' The 2 + 1 paradigm involves the use of both site and central readers, validated scoring criteria and multiple measures for blinding readers, all of which contribute to reducing bias and generating a reliable endoscopic subscore that reflects endoscopic disease severity. The paradigm can be utilized while maintaining a practical workflow compatible with an operationally feasible clinical trial. The 2 + 1 paradigm represents a logical approach to endoscopic assessment in IBD clinical trials, one that should be considered attractive to prospective sponsors, contract research organizations, key opinion leaders and regulatory authorities and be ready for implementation and further evaluation. PMID- 26361985 TI - Experts back genome editing in human embryo research. PMID- 26361986 TI - Progression of cognitive impairments in idiopathic REM sleep behaviour disorder. AB - BACKGROUND: Idiopathic REM (rapid eye movement) sleep behaviour disorder (iRBD) has been implicated in cognitive impairments, but there is little evidence about progression of cognitive dysfunction in iRBD. METHODS: A retrospective follow-up study with patients with iRBD was performed. Conversion to neurodegenerative disorders was analysed by Kaplan-Meier survival analysis. Neuropsychological test results at baseline were compared between patients with iRBD and healthy controls. 57 patients with iRBD were successfully followed up for changes of cognitive performance over time (follow-up duration 50.84+/-25.38 months; range 12-108 months). Factors affecting cognitive decline were evaluated with multiple regression analysis and the subgroup analysis for groups with and without conversion was carried out. RESULTS: Among 84 patients with iRBD, conversion occurred in 18 patients and conversion rates were estimated to be 9%, 18% and 35% at 3, 5 and 6 years from diagnosis of iRBD. Individuals with iRBD showed lower z scores at baseline than controls in Mini-Mental Status Examination, Trail Making Test A, constructional praxis and Executive Clock Drawing Task (CLOX2). Patients with non-converting iRBD showed significant performance decline in memory (p=0.003, Digit span forward) and a worsening tendency of executive functions (p=0.007, frontal assessment battery; p=0.012, Stroop test) at follow-up tests. Cognitive decline was associated with disease duration or follow-up duration, and lower executive function at baseline increased conversion risk (p=0.031). CONCLUSIONS: Patients with iRBD have cognitive impairments at baseline and progressive cognitive decline over time. Even in idiopathic cases without development of any neurodegenerative disease, degenerative changes in cognition seem to be under way. PMID- 26361987 TI - Conflicts of interest are bound to increase as GPs co-commission more primary care services, report warns. PMID- 26361989 TI - Outcomes of Patients with Respiratory Distress Treated with Bubble CPAP on a Pediatric Ward in Malawi. AB - OBJECTIVE: To describe the outcomes of infants and young children with respiratory distress when treated with a novel, low-cost, stand-alone bubble Continuous Positive Airway Pressure (bCPAP) system in a resource-limited setting. METHODS: A non-randomized, convenience sample study in a pediatric unit in Blantyre, Malawi, 2013. Patients weighing <=10 kg with respiratory distress were eligible. We compared outcomes for patients with bronchiolitis, pneumonia and Pneumocystis jiroveci pneumonia (PJP) after treatment with bCPAP. RESULTS: Seventy percent of patients treated with bCPAP survived. Outcomes were best for patients with bronchiolitis and worst for those with PJP. Most survivors (80%) showed improvement within 24 h. All treating physicians found bCPAP useful, leading to a change in practice. CONCLUSIONS: Bubble CPAP was most beneficial to patients with bronchiolitis. Children, who were going to get well, tended to get well quickly. Physicians believed the bCPAP system provided a higher level of care than nasal oxygen. PMID- 26361990 TI - Protective effects of the thiol compounds GSH and NAC against sulfur mustard toxicity in a human keratinocyte cell line. AB - Sulfur mustard (SM) is a chemical warfare agent causing blistering, inflammation and ulceration of the skin. Thiol compounds such as glutathione (GSH) and N acetylcysteine (NAC) have been suggested as potential antidotes. We investigated SM toxicity in a human keratinocyte cell line (HaCaT) and used GSH and NAC to counteract its cytotoxic effects. Cells were treated with 1, 5 or 10mM GSH or NAC and exposed to 30, 100 or 300MUM SM. Different treatment regimens were applied to model extra- and intra-cellular GSH/NAC effects on SM toxicity. Necrosis, apoptosis and interleukin-6 and -8 levels were determined 24h post-exposure. Necrosis and apoptosis increased with SM dose. Interleukin-6 and -8 production peaked at 100MUM and decreased at 300MUM probably due to reduced ability for interleukin biosynthesis. Intracellular GSH/NAC diminished necrosis induced by 100MUM SM. Extracellular GSH/NAC protected against necrosis and apoptosis induced by 100 and 300MUM SM. Interleukin-6 and -8 production, induced by 100MUM SM was reduced by GSH/NAC. However, low-dose GSH/NAC treatment of cells exposed to 300MUM SM led to increased interleukin production. Thus, moderately poisoned cells are mostly responsible for SM-induced secretion of pro-inflammatory cytokines. GSH and NAC treatment can reduce SM-induced toxic effects. Protective effects were more pronounced by extracellular GSH or NAC administration. Rescue of severely poisoned cells may result in a strong secretion of pro- inflammatory cytokines. In summary, thiol compounds such as GSH or NAC constitute a promising approach to improve the therapy for SM injury. Additional intervention to prevent adverse effects of interleukin production might be beneficial. PMID- 26361991 TI - Biotinidase deficiency: Spectrum of molecular, enzymatic and clinical information from newborn screening Ontario, Canada (2007-2014). AB - Untreated profound biotinidase deficiency results in a wide range of clinical features, including optic atrophy, cutaneous abnormalities, hearing loss and developmental delay. Ontario, Canada incorporated this treatable deficiency in newborn screening over the past 8years. This study elucidates the molecular, biochemical, and clinical findings from the pilot project. Information from initial screens, serum biotinidase activity level assays, molecular testing, and family history for 246 positive newborns screens were analyzed. A mutation spectrum was created for the province of Ontario, including common mutations such as D444H, D444H/A171T, Q456H, C33fs, and R157H. Individuals with partial deficiency were separated into 3 groups: D444H homozygotes (Group 1); compound heterozygotes for D444H with another profound allele (Group 2); compound heterozygotes with two non-D444H alleles (Group 3). Biochemical phenotype genotype associations in partial deficiency showed a significant difference in serum biotinidase activity in between any given two groups. Three children with partial deficiency discontinued biotin for varied lengths of time. Two of whom became symptomatic with abnormal gait, alopecia, skin rashes and developmental delay. A need for more congruency in diagnostic, treatment and educational practices was highlighted across the province. Heterogeneity and variation in clinical presentations and management was observed in patients with the partial deficiency. PMID- 26361992 TI - Adrenal gland volume assessed by magnetic resonance imaging in women with polycystic ovary syndrome. AB - PURPOSE: To determine adrenal gland volume (AGV) in women with polycystic ovary syndrome (PCOS) by comparison with healthy control subjects and to investigate the relationship between AGV and hormonal status. PATIENTS AND METHODS: AGV was measured on transverse sections of T1-weighted MRI imaging data in 27 PCOS patients and 40 age-matched control subjects for this prospectively designed study. A comparative analysis of AGV in PCOS and controls was performed and possible correlations between AGV and hormonal parameters were evaluated. RESULTS: PCOS patients had significantly larger AGV compared to controls ((11.7+/ 4.4 cm(3), 7.2+/-1.9 cm(3), respectively, P<0.001). A significant positive correlation was found between total AGV and dehydroepiandrosterone sulfate, 17-OH progesterone, and total and free testosterone levels in the PCOS group (r=+0.51, +0.48, +0.43, +0.62, respectively; P values<0.05). In addition, AGV was significantly negatively correlated with LH and LH/FSH ratio in the PCOS group (r= -0.55, P=0.02; r=-0.51, P=0.01, respectively). CONCLUSIONS: PCOS patients have significantly increased AGV as well as a positive correlation of AGV and androgens. We conclude that the assessment of AGV with MRI shows a significant correlation with the androgenic activity of the gland, and that hypertrophy of the adrenal gland may be involved in the pathogenesis of PCOS. PMID- 26361988 TI - Epithelial-mesenchymal transition: An emerging target in tissue fibrosis. AB - Epithelial-mesenchymal transition (EMT) is involved in a variety of tissue fibroses. Fibroblasts/myofibroblasts derived from epithelial cells contribute to the excessive accumulation of fibrous connective tissue in damaged tissue, which can lead to permanent scarring or organ malfunction. Therefore, EMT-related fibrosis cannot be neglected. This review highlights the findings that demonstrate the EMT to be a direct contributor to the fibroblast/myofibroblast population in the development of tissue fibrosis and helps to elucidate EMT related anti-fibrotic strategies, which may enable the development of therapeutic interventions to suppress EMT and potentially reverse organ fibrosis. PMID- 26361993 TI - An analysis of protocols and publications suggested that most discontinuations of clinical trials were not based on preplanned interim analyses or stopping rules. AB - OBJECTIVES: To investigate the frequency of interim analyses, stopping rules, and data safety and monitoring boards (DSMBs) in protocols of randomized controlled trials (RCTs); to examine these features across different reasons for trial discontinuation; and to identify discrepancies in reporting between protocols and publications. STUDY DESIGN AND SETTING: We used data from a cohort of RCT protocols approved between 2000 and 2003 by six research ethics committees in Switzerland, Germany, and Canada. RESULTS: Of 894 RCT protocols, 289 prespecified interim analyses (32.3%), 153 stopping rules (17.1%), and 257 DSMBs (28.7%). Overall, 249 of 894 RCTs (27.9%) were prematurely discontinued; mostly due to reasons such as poor recruitment, administrative reasons, or unexpected harm. Forty-six of 249 RCTs (18.4%) were discontinued due to early benefit or futility; of those, 37 (80.4%) were stopped outside a formal interim analysis or stopping rule. Of 515 published RCTs, there were discrepancies between protocols and publications for interim analyses (21.1%), stopping rules (14.4%), and DSMBs (19.6%). CONCLUSION: Two-thirds of RCT protocols did not consider interim analyses, stopping rules, or DSMBs. Most RCTs discontinued for early benefit or futility were stopped without a prespecified mechanism. When assessing trial manuscripts, journals should require access to the protocol. PMID- 26361994 TI - Using venlafaxine to treat behavioral disorders in patients with autism spectrum disorder. AB - OBJECTIVE: To test the efficacy of venlafaxine at a dose of 18.75 mg/day on the reduction of behavioral problems such as irritability and hyperactivity/noncompliance in patients with intellectual disabilities and autism spectrum disorder (ASD). Our secondary hypothesis was that the usual doses of zuclopenthixol and/or clonazepam would decrease in the venlafaxine-treated group. METHODS: In a randomized double-blind study, we compared six patients who received venlafaxine along with their usual treatment (zuclopenthixol and/or clonazepam) with seven patients who received placebo plus usual care. Irritability, hyperactivity/noncompliance, and overall clinical improvement were measured after 2 and 8 weeks, using validated clinical scales. RESULTS: Univariate analyses showed that the symptom of irritability improved in the entire sample (p = 0.023 after 2 weeks, p = 0.061 at study endpoint), although no difference was observed between the venlafaxine and placebo groups. No significant decrease in hyperactivity/noncompliance was observed during the study. At the end of the study, global improvement was observed in 33% of participants treated with venlafaxine and in 71% of participants in the placebo group (p = 0.29). The study found that decreased cumulative doses of clonazepam and zuclopenthixol were required for the venlafaxine group. Multivariate analyses (principal component analyses) with at least three combinations of variables showed that the two populations could be clearly separated (p b 0.05). Moreover, in all cases, the venlafaxine population had lower values for the Aberrant Behavior Checklist (ABC), Behavior Problems Inventory (BPI), and levels of urea with respect to the placebo group. In one case, a reduction in the dosage of clonazepam was also suggested. For an additional set of variables (ABC factor 2, BPI frequency of aggressive behaviors, hematic ammonia at Day 28, and zuclopenthixol and clonazepam intake), the separation between the two samples was statistically significant as was the Bartlett's test, but the Kaiser-Meyer-Olkin Measure of Sampling Adequacy was below the accepted threshold. This set of variables showed a reduction in the cumulative intake of both zuclopenthixol and clonazepam. CONCLUSION: Despite the small sample sizes, this study documented a statistically significant effect of venlafaxine. Moreover, we showed that lower doses of zuclopenthixol and clonazepam were needed in the venlafaxine group, although this difference was not statistically significant. This was confirmed by multivariate analyses, where this difference reached statistical significance when using a combination of variables involving zuclopenthixol. Larger-scale studies are recommended to better investigate the effectiveness of venlafaxine treatment in patients with intellectual disabilities and ASD. PMID- 26361995 TI - Prevalence and molecular types of Clostridium difficile isolates from faecal specimens of patients in a tertiary care centre. AB - Clostridium difficile infection (CDI) leads to considerable morbidity and mortality among hospitalized patients. Faecal specimens from 1110 hospitalized patients suspected for CDI were cultured for isolation of C. difficile and characterization of virulence genes. PCR was carried out for toxigenic genes tcdA, tcdB, cdtA and cdtB and PCR-RFLP for fliC and slpA genes. Of 174 (15.7%) C. difficile isolates, 121 (69.5%) were toxigenic, amongst which 68 (56.2%) also had both tcdA and tcdB genes. The remaining 53 (43.8%) of the isolates also had at least one of the toxin genes. Binary toxin genes (cdtA and cdtB) with only one of the two components were present in 16 (9.2%) of the 174 isolates. The other virulence genes - fliC and slpA - were present in 100% of the isolates. The most frequent PCR-RFLP type of fliC gene was type I (n = 101), followed by type VII (n = 49) and type III (n = 24). The slpA gene presented with three combinations of patterns. Characterization of virulence genes in C. difficile isolates is of extreme importance for epidemiological surveillance and control of outbreaks owing to the capacity of this bacterium to adapt to new environmental circumstances, leading to the emergence of new epidemic strains. PMID- 26361996 TI - Comparative proteome analysis across non-small cell lung cancer cell lines. AB - Non-small cell lung cancer (NSCLC) cell lines are widely used model systems to study molecular aspects of lung cancer. Comparative and in-depth proteome expression data across many NSCLC cell lines has not been generated yet, but would be of utility for the investigation of candidate targets and markers in oncogenesis. We employed a SILAC reference approach to perform replicate proteome quantifications across 23 distinct NSCLC cell lines. On average, close to 4000 distinct proteins were identified and quantified per cell line. These included many known targets and diagnostic markers, indicating that our proteome expression data represents a useful resource for NSCLC pre-clinical research. To assess proteome diversity within the NSCLC cell line panel, we performed hierarchical clustering and principal component analysis of proteome expression data. Our results indicate that general proteome diversity among NSCLC cell lines supersedes potential effects common to K-Ras or epidermal growth factor receptor (EGFR) oncoprotein expression. However, we observed partial segregation of EGFR or KRAS mutant cell lines for certain principal components, which reflected biological differences according to gene ontology enrichment analyses. Moreover, statistical analysis revealed several proteins that were significantly overexpressed in KRAS or EGFR mutant cell lines. PMID- 26361998 TI - Infectious disease surveillance in China. PMID- 26361997 TI - Inhibition of hepatitis C virus RNA replication by ISG15 does not require its conjugation to protein substrates by the HERC5 E3 ligase. AB - Chronic infection of the liver by hepatitis C virus (HCV) induces a range of host factors including IFN-stimulated genes such as ISG15. ISG15 functions as an antiviral factor that limits virus replication. Previous studies have suggested that ISG15 could influence HCV replication in both a positive and a negative manner. In this report, we determined the effect of ISG15 on HCV RNA replication in two independent cell lines that support viral genome synthesis by inhibiting ISG15 expression through small interfering RNA, short-hairpin RNA and CRISPR/Cas9 gene knockout approaches. Our results demonstrated that ISG15 impairs HCV RNA replication in both the presence and absence of IFN stimulation, consistent with an antiviral role for ISG15 during HCV infection. ISG15 conjugation to protein substrates typically requires the E3 ligase, HERC5. Our results showed that the inhibitory effect of ISG15 on HCV RNA replication does not require its conjugation to substrates by HERC5. PMID- 26361999 TI - Technique for the Characterization of Phospholipid Microbubbles Coatings by Transmission Electron Microscopy. AB - Gas microbubbles stabilized by a surfactant or polymer coating are of considerable clinical interest because of their imaging and drug delivery potential under ultrasound exposure. The utility of microbubbles for a given application is intrinsically linked to their structure and stability. These in turn are highly sensitive to coating composition and fabrication techniques. Various methods including fluorescence and atomic force microscopy have been applied to characterize microbubble properties, but direct observation of coating structure at the nanoscale still poses a considerable challenge. Here we describe a transmission electron microscopy (TEM) technique to observe the surface of microbubbles. Images from a series of phospholipid-coated microbubble systems, including those decorated with nanoparticles, are presented. They indicate that the technique enables visualization of the coating structure, in particular lipid discontinuities and nanoparticle distribution. This information can be used to better understand how microbubble surface structure relates to formulation and/or processing technique and ultimately to functionality. PMID- 26362000 TI - Motivational Interviewing to Reduce Substance Use in Adolescents with Psychiatric Comorbidity. AB - Substance use among adolescents with one or more psychiatric disorders is a significant public health concern. In this study, 151 psychiatrically hospitalized adolescents, ages 13-17 with comorbid psychiatric and substance use disorders, were randomized to a two-session Motivational Interviewing intervention to reduce substance use plus treatment as usual (MI) vs. treatment as usual only (TAU). Results indicated that the MI group had a longer latency to first use of any substance following hospital discharge relative to TAU (36 days versus 11 days). Adolescents who received MI also reported less total use of substances and less use of marijuana during the first 6 months post-discharge, although this effect was not significant across 12 months. Finally, MI was associated with a significant reduction in rule-breaking behaviors at 6-month follow-up. Future directions are discussed, including means of extending effects beyond 6 months and dissemination of the intervention to community-based settings. PMID- 26362001 TI - Hispanic Subgroups, Acculturation, and Substance Abuse Treatment Outcomes. AB - This study explored Hispanic subgroup differences in substance use treatment outcomes, and the relationship of acculturation characteristics to these outcomes. Data were from a multisite randomized clinical trial of motivational enhancement therapy versus treatment as usual in a sample of Spanish-speaking substance abusers. Participants were Cuban American (n=34), Mexican American (n=209), Puerto Rican (n=78), and other Hispanic American (n=54). Results suggested that Cuban Americans and individuals with more connection to Hispanic culture had lower treatment retention. Hispanics born in the U.S and those who spoke English at home had a lower percentage of days abstinent during weeks 5-16, although Puerto Ricans born in the U.S. and Cuban Americans living more years in the U.S. had a higher percentage of days abstinent in weeks 1-4 and 5-16, respectively. Results may inform future hypothesis-driven studies in larger Hispanic treatment seeking samples of the relationship between acculturation and treatment outcome. PMID- 26362002 TI - Referrals and Treatment Completion for Prescription Opioid Admissions: Five Years of National Data. AB - This study examines sources of referral for prescription opioid admission to substance use disorder treatment facilities and their relative completion success rates using secondary analysis of an existing data set (treatment episode datasets-discharge). Five years of data from public and private treatment facilities were extracted for client discharges with no prior treatment (N=2,909,884). Healthcare professionals account for very few referrals to treatment (<10%). Prescription opioid clients referred into treatment had lower treatment success compared to other substance clients and when referred by healthcare providers had lower success rates (OR=0.72, 95% CI 0.70-0.75) than clients from other referral sources. Fewer treatment referrals for prescription opioid misuse by healthcare providers and lower success rates are significant and timely findings due to the prevalence of prescription opioid misuse. Healthcare providers are well positioned to refer early for prescription opioid misuse and continue support of their patients during treatment. PMID- 26362003 TI - Biliary Fasciola gigantica infestation in a nonendemic area--An intraoperative surprise. AB - A 7year old girl infected with the zoonotic trematode, Fasciola gigantica is reported because of the extreme rarity of this condition in our region. Because of the overlap in symptomatology and radiological features, the more common amebic/pyogenic liver abscess in the initial hepatic migratory phase and later choledochal cyst/biliary ascariasis when the parasite was finally located in the extrahepatic bile ducts, were thought of delaying effective treatment. The diagnosis was confirmed only by surgical exploration. The characteristic contrast enhanced computed tomography scan features retrospectively identified were multiple clustered hypodense lesions in the liver with peripheral enhancement in the acute hepatic migratory phase, and periportal tracking in the previously affected areas of the liver with biliary dilatation and a linear hypointense lesion within the common bile duct in the chronic phase. Although a known association, she did not have eosinophilia. This child, who became symptomatic at the age of 5.5years, also appears to be one of the youngest patients reported with Fasciola gigantica. PMID- 26362004 TI - Sparing internal thoracic vessels in thoracoscopic or submuscular correction of pectus carinatum: A porcine model study. AB - BACKGROUND: External compression is used for pectus carinatum (PC) treatment, but many patients are noncompliant. Costal cartilage resection (CCR) has been described as an alternative, but these approaches sacrifice the internal thoracic arteries (ITA). We aim to assess the feasibility of CCR sparing ITA comparing thoracoscopic and subcutaneous endoscopic approaches. METHODS: Twelve pigs were used as models for surgical PC correction and randomized for 2 groups: thoracoscopy (T) and subcutaneous (subpectoralis) endoscopy (SP). In both groups, CCR from 3rd 4th and 5th ribs was performed avoiding ITA damage. ITA preservation was confirmed by Doppler-ultrasound as well as postmortem injection of methylene blue. Four persons evaluated the procedures being difficult, using a 6-item modified validated scale. RESULTS: In both techniques, the procedure was accomplished in all animals sparing ITAs. CCR was faster in T than in SP (49+/-5 vs. 65+/-16minutes, p<0.05). T was classified as easier than SP (p<0.001) with a significantly higher score for all items, especially better image and tissue handling. DISCUSSION: Sparing the ITAs during CCR for correction of PC is feasible in a porcine model and might be a goal in humans. The thoracoscopic approach allows for a faster and easier procedure. PMID- 26362005 TI - Central venous catheter repair is not associated with an increased risk of central line infection or colonization in intestinal failure pediatric patients. AB - PURPOSE: The intestinal failure (IF) population is dependent upon central venous catheters (CVC) to maintain minimal energy requirements for growth. Central venous catheter infections (CVCI) are frequent and an independent predictor of intestinal failure associated liver disease. A common complication in children with long-term CVC is the risk of line breakage. Given the often-limited usable vascular access sites in this population, it has been the standard of practice to perform repair of the broken line. Although widely practiced, it is unknown if this practice is associated with increased line colonization rates and subsequent line loss. METHODS: A retrospective review of our institutional IF population over the past 8years (2006-2014) was performed. Utilizing a prospectively constructed database, all pediatric patients (n=13, ages 0-17 years) with CVC dependency enrolled in the Children's Intestinal Rehabilitation Program with IF were included who underwent a repair and/or replacement procedure of their line. The control replacement group was CVCs that were replaced without being repaired (36), the experimental repair group was CVCs that were repaired (8). The primary outcome of interest was the mean number of days in each group from the intervention (replacement or repair) to line infection/colonization. Mann-Whitney tests for significance were performed with p-values <0.05 being the threshold value for significance. RESULTS: There were no catheter repair associated CVCI. The mean number of days from the replacement or repair of a CVC to its removal owing to infection/colonization was 210.0 and 162.8days respectively. There was no statistically significant difference between these groups in time to removal owing to line infection (p=0.55). CONCLUSION: Repair of central venous catheters in the pediatric population with intestinal failure does not lead to an increased rate of central venous catheter infection and should be performed when possible. PMID- 26362006 TI - Measuring Transcription Rate Changes via Time-Course 4-Thiouridine Pulse Labelling Improves Transcriptional Target Identification. AB - Identifying changes in the transcriptional regulation of target genes from high throughput studies is important for unravelling molecular mechanisms controlled by a given perturbation. When measuring global transcript levels only, the effect of the perturbation [e.g., transcription factor (TF) overexpression or drug treatment] on its target genes is often obscured by delayed feedback and secondary effects until the changes are fully propagated. As a proof of principle, we show that selective measuring of transcripts that are only synthesised after a perturbation [4-thiouridine (4sU) sequencing (4sU-seq)] is a more sensitive method to identify targets and time-dependent transcriptional responses than global transcript profiling. By metabolically labelling RNA in a time-course setup, we could vastly increase the sensitivity of MYCN target gene detection compared to traditional RNA sequencing. The validity of targets identified by 4sU-seq was demonstrated using chromatin immunoprecipitation sequencing and neuroblastoma microarray tumour data. Here, we describe the methodology, both molecular biology and computational aspects, required to successfully apply this 4sU-seq approach. PMID- 26362008 TI - Exocrine glands in the legs of the social wasp Vespula vulgaris. AB - This study brings a survey of the exocrine glands in the legs of Vespula vulgaris wasps. We studied workers, males, virgin queens as well as mated queens. A variety of 17 glands is found in the different leg segments. Among these, five glands are novel exocrine structures for social insects (trochanter-femur gland, ventrodistal tibial gland, distal tibial sac gland, ventral tibial gland, and ventral tarsomere gland). Most leg glands are present in the three leg pairs of all castes. This may indicate a mechanical function. This is likely for the numerous glands that occur near the articulation between the various leg segments, where lubricant production may be expected. Other possible functions include antenna cleaning, acting as a hydraulic system, or pheromonal. Further research including leg-related behavioural observations and chemical analyses may help to clarify the functions of these glandular structures in the legs. PMID- 26362007 TI - Three-Dimensional Structure of Vertebrate Muscle Z-Band: The Small-Square Lattice Z-Band in Rat Cardiac Muscle. AB - The Z-band in vertebrate striated muscle crosslinks actin filaments of opposite polarity from adjoining sarcomeres and transmits tension along myofibrils during muscular contraction. It is also the location of a number of proteins involved in signalling and myofibrillogenesis; mutations in these proteins lead to myopathies. Understanding the high-resolution structure of the Z-band will help us understand its role in muscle contraction and the role of these proteins in the function of muscle. The appearance of the Z-band in transverse-section electron micrographs typically resembles a small-square lattice or a basketweave appearance. In longitudinal sections, the Z-band width varies more with muscle type than species: slow skeletal and cardiac muscles have wider Z-bands than fast skeletal muscles. As the Z-band is periodic, Fourier methods have previously been used for three-dimensional structural analysis. To cope with variations in the periodic structure of the Z-band, we have used subtomogram averaging of tomograms of rat cardiac muscle in which subtomograms are extracted and compared and similar ones are averaged. We show that the Z-band comprises four to six layers of links, presumably alpha-actinin, linking antiparallel overlapping ends of the actin filaments from the adjoining sarcomeres. The reconstruction shows that the terminal 5-7nm of the actin filaments within the Z-band is devoid of any alpha actinin links and is likely to be the location of capping protein CapZ. PMID- 26362009 TI - Functional anatomy of the explosive defensive system of bombardier beetles (Coleoptera, Carabidae, Brachininae). AB - This paper provides the first comparative anatomical study of the explosive pygidial defensive system of bombardier beetles in species classified in three brachinine subtribes: Brachinus (Brachinina), Pheropsophus (Pheropsophina) and Aptinus (Aptinina). We investigated the morphology and ultrastructure of this system using optical, fluorescence, and focused ion beam (FIB/SEM) microscopy. In doing so, we characterized and comparatively discussed: (1) the ultrastructure of the gland tissues producing hydroquinones and hydrogen peroxide (secretory lobes), and those producing catalases and peroxidases (accessory glands); (2) the complex anatomy of the collecting duct; (3) the arrangement of the muscular bundles and the folding of the cuticle of the reservoir, suggesting a functional division of this chamber (dynamic part and storage part); (4) the great structural diversity of sculpticles inside the reaction chamber, where we could recognize six main types of microsculpture located in specific districts of the chamber. Additionally, using fluorescence microscopy, we highlighted the presence of resilin in two structures strongly subjected to mechanical stress during the discharge, the valve and the turrets of the reaction chamber. The results of this paper give a solid anatomic overview of the most popular beetle defensive system, contributing to the debate on its evolution within the Carabidae. PMID- 26362010 TI - Tarsomere and distal tibial glands: structure and potential roles in termites (Isoptera: Rhinotermitidae, Termitidae). AB - Social insects have numerous exocrine glands, but these organs are understudied in termites compared to hymenopterans. The tarsomere and distal tibial glands of the termites Heterotermes tenuis, Coptotermes gestroi and Silvestritermes euamignathus were investigated by scanning and transmission electron microscopy. Pore plates are visible in scanning micrographs on the distal tibial surfaces and on the ventral surface of the first and second tarsomeres of workers of H. tenuis and C. gestroi. In contrast, workers of S. euamignathus have isolated pores spread throughout the ventral surfaces of the first, second, and third tarsomeres and the distal tibia. In all three species each pore corresponds to the opening of a class-3 secretory unit, composed of one secretory and one canal cell. Clusters of class-3 glandular cells are arranged side by side underneath the cuticle. The main characteristics of these exocrine glands include their presence on all the legs and the electron-lucent secretion in the secretory cells. Possible functions of these glands are discussed. PMID- 26362011 TI - Toxic epidermal necrolysis caused by acetaminophen featuring almost 100% skin detachment: Acetaminophen is associated with a risk of severe cutaneous adverse reactions. AB - Toxic epidermal necrolysis (TEN) is an adverse reaction that can be induced by various drugs; the associated mortality rate is 20-25%. A previous report showed a weak association between TEN and acetaminophen. Recently, the US Food and Drug Administration declared that acetaminophen is associated with a risk of serious skin reactions, including TEN. Here, we describe the case of a 43-year-old Japanese woman with TEN caused by acetaminophen. She had poorly controlled ulcerative colitis and was treated with high doses of prednisolone, infliximab, acetaminophen and lansoprazole. Nine days after administrating acetaminophen, targetoid erythematous and bullous lesions appeared on the patient's trunk, palms and the soles of her feet. The skin lesions expanded rapidly; within 3 weeks, skin detachment was detected across nearly 100% of the patient's body. However, no mucosal involvement of the eyes, oral cavity or genitalia was found. We performed lymphocyte transformation tests using various drugs; however, a high stimulation index was obtained only with acetaminophen. The patient recovered following treatment with plasmapheresis, i.v. immunoglobulin therapy, topical medication and supportive therapy. Acetaminophen is included in many prescription and over-the-counter products; thus, clinicians should monitor their patients for severe drug reactions, including TEN. PMID- 26362012 TI - Aromatic residues in RNase T stack with nucleobases to guide the sequence specific recognition and cleavage of nucleic acids. AB - RNase T is a classical member of the DEDDh family of exonucleases with a unique sequence preference in that its 3'-to-5' exonuclease activity is blocked by a 3' terminal dinucleotide CC in digesting both single-stranded RNA and DNA. Our previous crystal structure analysis of RNase T-DNA complexes show that four phenylalanine residues, F29, F77, F124, and F146, stack with the two 3'-terminal nucleobases. To elucidate if the pi-pi stacking interactions between aromatic residues and nucleobases play a critical role in sequence-specific protein nucleic acid recognition, here we mutated two to four of the phenylalanine residues in RNase T to tryptophan (W mutants) and tyrosine (Y mutants). The Escherichia coli strains expressing either the W mutants or the Y mutants had slow growth phenotypes, suggesting that all of these mutants could not fully substitute the function of the wild-type RNase T in vivo. DNA digestion assays revealed W mutants shared similar sequence specificity with wild-type RNase T. However, the Y mutants exhibited altered sequence-dependent activity, digesting ssDNA with both 3'-end CC and GG sequences. Moreover, the W and Y mutants had reduced DNA-binding activity and lower thermal stability as compared to wild-type RNase T. Taken together, our results suggest that the four phenylalanine residues in RNase T not only play critical roles in sequence-specific recognition, but also in overall protein stability. Our results provide the first evidence showing that the pi-pi stacking interactions between nucleobases and protein aromatic residues may guide the sequence-specific activity for DNA and RNA enzymes. PMID- 26362013 TI - Continuous infusion of propofol in calves: bispectral index and hemodynamic effects. AB - OBJECTIVE: To assess the bispectral index (BIS) and the hemodynamic effects of propofol administered by continuous infusion at different rates in calves. STUDY DESIGN: Experimental crossover study. ANIMALS: Eight intact male Dutch calves, aged 6-12 months and weighing 84-124 kg. METHODS: The calves were anesthetized with propofol (5 mg kg(-1) ) intravenously (IV), and after endotracheal intubation, positioned in right lateral recumbency and allowed to breathe ambient air. Anesthesia was maintained by continuous infusion of propofol, administered IV with an infusion pump at 0.6 mg kg(-1) minute(-1) (treatment G6) or 0.8 mg kg(-1) minute(-1) IV (treatment G8), for 60 minutes. The eight animals were anesthetized twice, 1 week apart. The following hemodynamic variables and BIS were assessed before the induction of anesthesia (baseline) and 15, 30, 45, and 60 minutes after beginning the infusion of propofol: heart rate, systolic, diastolic and mean arterial pressures, cardiac output, mean pulmonary artery pressure, cardiac index, stroke index, pulmonary vascular resistance index, and systemic vascular resistance index, BIS, electromyography, and signal quality index. RESULTS: The continuous infusions of propofol at different rates did not alter BIS variables during the infusion time between dose rates, and no clinically significant hemodynamic changes were observed. CONCLUSIONS AND CLINICAL RELEVANCE: A continuous infusion of propofol at 0.6 or 0.8 mg kg(-1) minute(-1) caused minimal hemodynamic changes without clinical relevance in calves. BIS could not be reliably used to discriminate the anesthetic depth during the two propofol infusion rates. PMID- 26362014 TI - Adult thymic epithelial cell (TEC) progenitors and TEC stem cells: Models and mechanisms for TEC development and maintenance. AB - The thymus is the primary lymphoid organ for generating self-restricted and self tolerant functional T cells. Its two distinct anatomical regions, the cortex and the medulla, are involved in positive and negative selection, respectively. Thymic epithelial cells (TECs) constitute the framework of this tissue and function as major stromal components. Extensive studies for more than a decade have revealed how TECs are generated during organogenesis; progenitors specific for medullary TECs (mTECs) and cortical TECs (cTECs) as well as bipotent progenitors for both lineages have been identified, and the signaling pathways required for the development and maturation of mTECs have been elucidated. However, little is known about the initial commitment of mTECs and cTECs during ontogeny, and how regeneration of both lineages is sustained in the postnatal/adult thymus. Recently, stem cell activities in TECs have been demonstrated, and TEC progenitors have been identified in the postnatal thymus. In this review, recent advances in studying the development and maintenance of TECs are summarized, and the possible mechanisms of thymic regeneration and involution are discussed. PMID- 26362015 TI - Novel Inhibitors of Ornithine Decarboxylase of Leishmania Parasite (LdODC): The Parasite Resists LdODC Inhibition by Overexpression of Spermidine Synthase. AB - Ornithine decarboxylase (LdODC), a key enzyme in polyamine biosynthesis in Leishmania donovani, catalyzes the conversion of ornithine to putrescine that is finally used for synthesis of spermidine and other polyamines. Inhibition of ornithine decarboxylase is likely to deplete the parasite trypanothione and may result in increased reactive oxygen species (ROS). Sequence as well as structure of LdODC and human ODC shows significant difference; therefore, we have identified novel specific inhibitors of LdODC. These inhibitors are able to inhibit recombinant LdODC and decrease intracellular putrescine concentration showing target specificity. The Ki values of LdODC inhibition do not correlate with IC50 values in Leishmania promastigote possibly due to different stability/pharmacokinetics. These inhibitors, except compound M-5, have only minor effect on Leishmania promastigotes, and IC50 values are several folds higher as compared to Ki values. In case of compound M-5, IC50 value is less than Ki value indicating that the compound may have additional targets. Our studies suggest that the parasite resists these LdODC inhibitors by overexpression of spermidine synthase mRNA. PMID- 26362016 TI - Review of the role of sentinel node biopsy in cutaneous head and neck melanoma. AB - Sentinel node biopsy (SNB) is recommended for selected melanoma patients in many parts of the world. This review examines the evidence surrounding the accuracy and prognostic value of SNB and completion neck dissection in head and neck melanoma. Sentinel nodes were identified in an average of 94.7% of head and neck cases compared with 95.3-100% in all melanoma cases. More false-negative sentinel nodes were found in head and neck cases. A positive sentinel node was associated with both lower disease-free survival (53.4 versus 83.2%) and overall survival (40 versus 84%). We conclude that SNB should be offered to all patients with intermediate and high-risk melanomas in the head and neck area. To date, evidence does not exist to demonstrate the safety of avoiding completion lymph node dissection in sentinel node-positive patients with head and neck melanoma. PMID- 26362017 TI - Treatment Resistant and Resistant to Treatment? Evaluation of 40 Alcohol Dependent Patients Admitted for Involuntary Treatment. AB - AIMS: To describe the clinical outcomes for a group of patients with severe alcohol dependence discharged from an Involuntary Drug and Alcohol Treatment (IDAT) program. METHODS: Forty patients admitted to an inpatient IDAT program were prospectively followed up over 6 months using standardized questionnaires. RESULTS: Patients had high rates of mental health comorbidities (97.5%), cortical atrophy (40%) and socioeconomic disadvantage (92.5% were beneficiaries). Six months after discharge, 25% of patients were abstinent and living in the community and 17.5% had notably reduced alcohol use. A further 7.5% were abstinent due to involuntary hospitalization. A total of 10% of patients were deceased and 40% of patients had relapsed or were lost to follow-up. Number of admissions and admission days reduced by 51 and 45% respectively for the 17 abstinent or improved community-based patients. A total of 82% of this patient group were actively engaged with an Assertive Community Treatment (ACT) team. CONCLUSIONS: While patient numbers are small, treatment responsiveness was evident for 42.5% of patients, most of whom were followed up with ACT. Evaluation with a comparator group is required to determine whether outcomes are a function of involuntary treatment or an assertive treatment approach. PMID- 26362018 TI - Minimally invasive in tumor multidrug comparative analysis with contrast-enhanced MRI in mice. AB - PURPOSE: To facilitate decision making in the oncology clinic, technologies have recently been developed to independently inject and assess multiple anticancer agents directly in a patient's tumor. To increase the flexibility of this approach beyond histological readouts of response, contrast-enhanced MRI was evaluated for the detection of cell death in living tumors after injection. METHODS: A six-needle arrayed microinjection device designed to provide head-to head comparisons of chemotherapy responses in living tumors was used. Xenografted non-Hodgkin lymphoma tumors in athymic Nude-Foxn1(nu) mice were injected either with different doses of vincristine or with one needle each of vincristine, doxorubicin, bendamustine, prednisolone, mafosfamide, and a vehicle control. To assess drug responses, measurements of enhancement by T1-weighted contrast enhanced MRI were made for individual sites at 24, 48, and 72 h after injection. For comparison, histological evaluations of cell death were obtained after tumor resection. RESULTS: Measurements of MRI enhancement at injection sites showed a significant (P < 0.001) positive regression slope as a function of vincristine dose. Average MRI measurements were closely correlated with cell death by hematoxylin and eosin staining (R = 0.81; P = 0.001). CONCLUSION: Contrast enhanced MRI has the potential to replace or augment histological analyses of tumor responses to microinjected doses of chemotherapy agents with potential application in selecting optimal chemotherapy regimens. Magn Reson Med 76:946 952, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26362020 TI - Glial fibrillary acidic protein (GFAP) shows circadian oscillations in crayfish Procambarus clarkii putative pacemakers. AB - Although several studies of glia have examined glial fibrillary acid protein (GFAP) and its relationship to the circadian rhythms of different organisms, they have not explored the daily GFAP oscillations in the putative pacemakers of the crayfish Procambarus clarkii or in other crustaceans. In this study we investigated the daily variations in GFAP concentrations in the eyestalk and brain, which are considered to be putative pacemakers in adult P. clarkii. In both structures, the glial GFAP was quantified using the indirect enzyme-linked immunosorbent assay (ELISA), and double labeling immunofluorescence was used to detect it and its co-localization with protein Period (PER), an important component of the circadian clock, in various regions of both structures. The ELISA results were analyzed using Cosinor and one-way ANOVA with Bonferroni and Scheffe's post hoc tests. The results of this analysis showed that the GFAP levels present circadian oscillations in both structures. Moreover, GFAP was localized in different structures of the eyestalk and brain; however, co localization with PER occurred only in the lamina ganglionaris, specifically in the cartridges of the eyestalk and in some of the cluster 9 brain cells. These results suggest that as in other invertebrates and vertebrates, glial cells could be involved in the circadian system of P. clarkii; however, thus far we cannot know whether the glial cells are only effectors, participate in afferent pathways, or are part of the circadian clock. PMID- 26362019 TI - Splicing promotes the nuclear export of beta-globin mRNA by overcoming nuclear retention elements. AB - Most current models of mRNA nuclear export in vertebrate cells assume that an mRNA must have specialized signals in order to be exported from the nucleus. Under such a scenario, mRNAs that lack these specialized signals would be shunted into a default pathway where they are retained in the nucleus and eventually degraded. These ideas were based on the selective use of model mRNA reporters. For example, it has been shown that splicing promotes the nuclear export of certain model mRNAs, such as human beta-globin, and that in the absence of splicing, the cDNA-derived mRNA is retained in the nucleus and degraded. Here we provide evidence that beta-globin mRNA contains an element that actively retains it in the nucleus and degrades it. Interestingly, this nuclear retention activity can be overcome by increasing the length of the mRNA or by splicing. Our results suggest that contrary to many current models, the default pathway for most intronless RNAs is to be exported from the nucleus, unless the RNA contains elements that actively promote its nuclear retention. PMID- 26362021 TI - Structure-Binding Effects: Comparative Binding of 2-Anilino-6 naphthalenesulfonate by a Series of Alkyl- and Hydroxyalkyl-Substituted beta Cyclodextrins. AB - Cyclodextrins (CDs) are the most widely used organic hosts for the inclusion of guest molecules. CDs can be readily modified through substitutions of the hydroxyl groups, and these modified CDs can have different host binding properties compared to those of parent CDs. However, only relatively few systematic studies of the effects of chemical substitution on CD binding ability have been reported thus far. In this paper, we report the study of the binding properties of five different analytically pure modified beta-cyclodextrin (beta CD) hosts (substituted with alkyl and/or hydroxyalkyl groups) with 2-anilino-6 naphthalenesulfonate (2,6-ANS) as guest. Binding constants for the formation of the inclusion complex between 2,6-ANS and each CD were determined using both fluorescence spectroscopy and capillary electrophoresis. Addition of modified CDs to an aqueous solution of 2,6-ANS resulted in significant enhancement of the fluorescence intensity of 2,6-ANS, as well as a significant spectral blue shift, indicative of inclusion. Inclusion of 2,6-ANS within the CD cavity was confirmed by NMR spectroscopy. Substitution at position 3 decreased the magnitude of the binding constants, while alkyl or hydroxylalkyl substitution of the primary hydroxyl at position 6 increased the magnitude of the binding constant in all cases, in relation with increasing length of the alkyl chain linker. In addition, binding constants decreased with solvent polarity when increasing amounts of methanol were added. Structure-binding correlations for CDs based on these binding constant results are presented and discussed. PMID- 26362022 TI - Determination of the toxicity of intravitreal minocycline in rabbit eyes. AB - PURPOSE: To evaluate the retinal toxicity of intravitreal minocycline in rabbit eyes. METHODS: Intravitreal injection of minocycline with concentrations of 1000, 500, 250, 125 and 62.5 MUg in 0.1 ml was performed in 10 New Zealand albino rabbits. Each concentration was injected into two rabbit eyes. For each dose, normal saline was injected in one contralateral eye and the other fellow eye remained non-injected. Electrophysiologic testing was performed before and 4 weeks after injections. The eyes were enucleated 4 weeks after injections and examined using light microscopy. RESULTS: The clinical examination was unremarkable after injections. Electroretinography recordings were significantly affected at all doses in at least one of the a- or b-waves of photopic or scotopic responses. Histopathologic examination revealed marked atrophy and loss of integrity in all retinal layers in all minocycline injected eyes. Contralateral eyes were normal. CONCLUSION: In our study, intravitreal minocycline was toxic to the retina in albino rabbits even at a concentration of 62.5 ug/0.1 ml. PMID- 26362023 TI - A study on the association of rs7950273 polymorphism in the PDGFD with ischaemic stroke in the Chinese Han population. AB - BACKGROUND: The association between the platelet-derived growth factor D (PDGFD) gene and atherosclerosis has been widely proven, whereas the relationship between the PDGFD gene and ischaemic stroke remains unconfirmed. AIM: A case-control study was performed to further evaluate the association of the C -> G mutation of rs7950273 in the PDGFD gene with ischaemic stroke (IS) in a Chinese Han population. SUBJECTS AND METHODS: This study recruited 3033 cases and 2807 controls from general hospitals in the southern, central and northern areas of China. The MGB probe and Taqman 7900HT Sequence Detection System were applied for genotyping. RESULTS: Genotype was not significantly associated with ischaemic stroke in total. After adjustment for gender, age, BMI, hypertension, diabetes mellitus and smoking, the CG and GG genotypes were still not associated with ischaemic stroke (p = 0.892 and p = 0.582 for CG and GG, respectively). CONCLUSION: This study suggests that the polymorphism of rs7950273 in the PDGFD gene is not associated with ischaemic stroke in the Chinese Han population. Further studies on the gene-gene and gene-environment interactions for the PDGFD gene and ischaemic stroke are needed. PMID- 26362024 TI - Aging in the Shadow of Violence: A Phenomenological Conceptual Framework for Understanding Elderly Women Who Experienced Lifelong IPV. AB - This article suggests a heuristic framework for understanding elderly women's "lived experience" of lifelong intimate partner violence (IPV). This framework is based on the phenomenological qualitative studies of 31 women, aged 60-83, using a semistructured interview guide. From the results, a matrix emerged built on two axes. The first axis consists of three phenomenological dimensions: suffering, a "ticking clock," and life wisdom. The second axis consists of four themes that emerged from the content analysis: loneliness, regret, being in a state of waiting, and being a living monument to perpetual victimhood. The practical implications of these phenomenological findings are then discussed. PMID- 26362025 TI - Inhibitory activity of isoniazid and ethionamide against Cryptococcus biofilms. AB - In recent years, the search for drugs to treat systemic and opportunistic mycoses has attracted great interest from the scientific community. This study evaluated the in vitro inhibitory effect of the antituberculosis drugs isoniazid and ethionamide alone and combined with itraconazole and fluconazole against biofilms of Cryptococcus neoformans and Cryptococcus gattii. Antimicrobials were tested at defined concentrations after susceptibility assays with Cryptococcus planktonic cells. In addition, we investigated the synergistic interaction of antituberculosis drugs and azole derivatives against Cryptococcus planktonic cells, as well as the influence of isoniazid and ethionamide on ergosterol content and cell membrane permeability. Isoniazid and ethionamide inhibited both biofilm formation and viability of mature biofilms. Combinations formed by antituberculosis drugs and azoles proved synergic against both planktonic and sessile cells, showing an ability to reduce Cryptococcus biofilms by approximately 50%. Furthermore, isoniazid and ethionamide reduced the content of ergosterol in Cryptococcus spp. planktonic cells and destabilized or permeabilized the fungal cell membrane, leading to leakage of macromolecules. Owing to the paucity of drugs able to inhibit Cryptococcus biofilms, we believe that the results presented here might be of interest in the designing of new antifungal compounds. PMID- 26362026 TI - Regulation of cytokinesis by membrane trafficking involving small GTPases and the ESCRT machinery. AB - During cell division, cells undergo membrane remodeling to achieve changes in their size and shape. In addition, cell division entails local delivery and retrieval of membranes and specific proteins as well as remodeling of cytoskeletons, in particular, upon cytokinetic abscission. Accumulating lines of evidence highlight that endocytic membrane removal from and subsequent membrane delivery to the plasma membrane are crucial for the changes in cell size and shape, and that trafficking of vesicles carrying specific proteins to the abscission site participate in local remodeling of membranes and cytoskeletons. Furthermore, the endosomal sorting complex required for transport (ESCRT) machinery has been shown to play crucial roles in cytokinetic abscission. Here, the author briefly overviews membrane-trafficking events early in cell division, and subsequently focus on regulation and functional significance of membrane trafficking involving Rab11 and Arf6 small GTPases in late cytokinesis phases and assembly of the ESCRT machinery in cytokinetic abscission. PMID- 26362027 TI - Biomarker of Early Glomerular Injury in Pre-eclampsia. AB - OBJECTIVES: Nephrin is an integral part of podocytes that together with endothelial cells and the basement form the glomerular filtration barrier. Placental ischemia triggers a cascade of events that ultimately result in endothelial malfunction, hypertension, podocytopathy and fetal compromise. METHODS: We review the literature to determine if urine nephrin measurements could serve as a useful biomarker to detect early podocyte injury in pre eclampsia. RESULTS: Our search identifies eight studies published to date. The findings of these studies demonstrate that urine nephrin excretion plays a critical role in the pathogenesis of proteinuria during pre-eclampsia and that this is a good indicator of glomerular injury. CONCLUSION: There is thus an urgent need for a large multi-centre clinical study using standardized recruitment criteria to determine the full potential of this biomarker in clinical practice. PMID- 26362028 TI - Introduction. PMID- 26362030 TI - Editorial: Chemometrics in Drug Discovery. PMID- 26362029 TI - A transcriptomic analysis of bermudagrass (Cynodon dactylon) provides novel insights into the basis of low temperature tolerance. AB - BACKGROUND: Cold stress is regarded as a key factor limiting widespread use for bermudagrass (Cynodon dactylon). Therefore, to improve cold tolerance for bermudagrass, it is urgent to understand molecular mechanisms of bermudagrass response to cold stress. However, our knowledge about the molecular responses of this species to cold stress is largely unknown. The objective of this study was to characterize the transcriptomic response to low temperature in bermudagrass by using RNA-Seq platform. RESULTS: Ten cDNA libraries were generated from RNA samples of leaves from five different treatments in the cold-resistant (R) and the cold-sensitive (S) genotypes, including 4 degrees C cold acclimation (CA) for 24 h and 48 h, freezing (-5 degrees C) treatments for 4 h with or without prior CA, and controls. When subjected to cold acclimation, global gene expressions were initiated more quickly in the R genotype than those in the S genotype. The R genotype activated gene expression more effectively in response to freezing temperature after 48 h CA than the S genotype. The differentially expressed genes were identified as low temperature sensing and signaling-related genes, functional proteins and transcription factors, many of which were specifically or predominantly expressed in the R genotype under cold treatments, implying that these genes play important roles in the enhanced cold hardiness of bermudagrass. KEGG pathway enrichment analysis for DEGs revealed that photosynthesis, nitrogen metabolism and carbon fixation pathways play key roles in bermudagrass response to cold stress. CONCLUSIONS: The results of this study may contribute to our understanding the molecular mechanism underlying the responses of bermudagrass to cold stress, and also provide important clues for further study and in-depth characterization of cold-resistance breeding candidate genes in bermudagrass. PMID- 26362031 TI - The Muller-Lyer illusion in the teleost fish Xenotoca eiseni. AB - In the Muller-Lyer illusion, human subjects usually see a line with two inducers at its ends facing outwards as longer than an identical line with inducers at its ends facing inwards. We investigate the tendency for fish to perceive, in suitable conditions, line length according to the Muller-Lyer illusion. Redtail splitfins (Xenotoca eiseni, family Goodeidae) were trained to discriminate between two lines of different length. After reaching the learning criterion, the fish performed test trials, in which they faced two lines (black or red) of identical length, differing only in the context in terms of arrangement of the inducers, which were positioned at the ends of the line, either inward, outward, or perpendicular. Fish chose the stimulus that appear to humans as either longer or shorter, in accordance with the prediction of the Muller-Lyer illusion, consistently with the condition of the training. These results show that redtail splitfins tend to be subject to this particular illusion. The results of the study are discussed with reference to similar studies concerning the same illusion as recently observed in fish. Contrasting results are presented. The significance of the results in light of their possible evolutionary implications is also discussed. PMID- 26362037 TI - Negative Social Relationships Predict Posttraumatic Stress Symptoms Among War Affected Children Via Posttraumatic Cognitions. AB - Post traumatic cognitions (PTCs) are important determinants of post traumatic stress symptoms (PTS symptoms). We tested whether risk factors of PTS symptoms (trauma, demographics, social and family-related factors) predict PTCs and whether PTCs mediate the association between risk factors and PTS symptoms among war-affected children. The participants were 240 Palestinian children 10-12 years old, half boys and half girls, and their parents. Children reported about psychological maltreatment, sibling and peer relations, war trauma, PTCs, PTS symptoms, and depression. Parents reported about their socioeconomic status and their own PTS symptoms. The associations between the variables were estimated in structural equation models. In models which included all the variables, PTCs were predicted by and mediated the effects of psychological maltreatment, war trauma, sibling conflict, and peer unpopularity on PTS symptoms. Other predictors had statistically non-significant effects. Psychological maltreatment had the largest indirect effect (b* = 0.29, p = 0.002) and the indirect effects of war trauma (b* = 0.10, p = 0.045), sibling conflict (b* = 0.10, p = 0.045), and peer unpopularity (b* = 0.10, p = 0.094) were lower and about the same size. Age salient social relationships are potentially important in the development of both PTCs and PTS symptoms among preadolescents. Furthermore, PTCs mediate the effects of the risk factors of PTS symptoms. The causality of the associations among the variables is not established but it could be studied in the future with interventions which improve the negative aspects of traumatized children's important social relationships. PMID- 26362038 TI - Jejuia marina nov., isolated from gravel adjacent to Geommeolle beach on Udo Island, South Korea. AB - A bacterial strain, JH03(T), was isolated from gravel adjacent to Geommeolle beach on Udo Island, South Korea. The cells were Gram-stain-negative, aerobic, non-motile and rod shaped. The ranges of temperature, pH and NaCl concentration for growth of the bacterium were 10-45 degrees C, pH 6.0-9.5 and 0.5-5.0 % (w/v), respectively. The major fatty acids of the bacterium were iso-C(15:0) (15.4 %), iso-C(15:1) G (14.1 %), iso-C(16:0) 3-OH (14.1 %), iso-C(17:0) 3-OH (11.5 %) and anteiso-C(15:0) (11.3 %). The major isoprenoid quinone was MK-6. The polar lipids included phosphatidylethanolamine, two unidentified amino lipids and three unidentified lipids. The DNA G+C content was 34.2 mol%. The phylogenetic analysis of the 16S rRNA gene sequences showed that strain JH03(T) was most closely related to Jejuia pallidilutea EM39(T) (96.5 % sequence similarity). Based on the polyphasic analysis, strain JH03(T) is a novel species of the genus Jejuia, for which the name Jejuia marina sp. nov. is proposed. The type strain is JH03(T) (= KCTC 42342(T) = JCM 30601(T)). PMID- 26362039 TI - Excellent short-term results of hip resurfacing in a selected population of young patients. AB - BACKGROUND: Hip resurfacing (HR) is an alternative option to total hip arthroplasty (THA) in a population of selected patients (young and/or active). HYPOTHESIS: The short-term survivorship rate is as least as good as that for THA with no abnormal increase in serum metal ion levels. MATERIALS AND METHODS: A continuous prospective series of 502 hip resurfacings in 481 patients mean age 48.7 years old (+/-10.3; 18-68) (Conserve Plus, Wright Medical Technology) was analyzed clinically, radiologically and biologically (total blood chrome, cobalt and titanium metal ion levels). Mean follow up was 4.1 years (1.9-4.9). RESULTS: There were no dislocations. There were 5 cases of revision surgery with component replacement (including 2 infections). Implant survivorship using implant removal as the criteria (excluding infection) was 99.4% at 4 years (CI 95%: 98.1-99.8). The evaluation of metal ion levels showed a significant increase in cobalt from a preoperative level of 0.24 MUg/L (0.01-3.6) to 0.86 MUg/L (0.01-5.7) at the final follow-up (P<0.001). Chrome and titanium levels went from 0.68 MUg/L (0.01-4.4) and 2.36 MUg/L (0.39-7) to 1.28 MUg/L (0.1-5.5) and 4.49 MUg/L (1.29-8.21) respectively (P<0.001). All clinical scores had significantly improved at the final follow-up. Mean frontal plane cup inclination was 42.7 degrees (35-62). DISCUSSION: In a selected population of young and/or active patients, the short term results of hip resurfacing are excellent. At the postoperative 4-year follow up the rate of complications (in particular the absence of dislocations) was less than that for THA in young and/or active patients. Certain conditions must be respected to obtain these results; frontal plane cup inclination of between 40 and 45 degrees , a femoral head diameter of at least 48 mm and good quality femoral bone. LEVEL OF EVIDENCE: IV. PMID- 26362040 TI - Treatment of Freiberg's disease by Gauthier's dorsal cuneiform osteotomy: Retrospective study of 30 cases. AB - INTRODUCTION: Freiberg's disease is osteonecrosis of the dorsal side of a metatarsal head. The gold-standard surgical treatment is the osteotomy procedure first described by Gauthier. HYPOTHESIS: Gauthier osteotomy for Freiberg's disease will restore the joint space and lead to long-term clinical improvement. A retrospective study was carried out to verify this hypothesis. MATERIAL AND METHODS: This study involved 30 consecutive cases treated by a single surgeon in 28 patients having a mean age of 61.2 years. These patients underwent the Gauthier osteotomy procedure with one or two dorsal staples used for fixation. Patients were reviewed 15 days, 45 days and 3 months after the procedure, and then at the last follow-up to look for any complications and determine patient satisfaction, the AOFAS score, metatarsophalangeal range of motion (ROM), sphericity of the metatarsal head, bone union and metatarsal shortening. RESULTS: The average follow-up was 6.5 years +/- 2.2. The second metatarsal was affected in 27 cases and the third metatarsal in 3 cases. Discomfort related to the staples was noted in five cases; the staples were removed in three of them. There was one case of severe stiffening (< 20 degrees ROM). At the last follow-up, 17 cases were very satisfied, 11 were satisfied and 2 were moderately satisfied. The average AOFAS score was 83.8 points +/- 11.8 at the last follow-up. A mean loss of 15 degrees plantar flexion and 10 degrees dorsiflexion was noted. Bone union and metatarsal head sphericity were achieved in all cases. The average shortening was 2 mm +/- 1.4. CONCLUSIONS: The Gauthier osteotomy procedure results in recovery of the metatarsal head's sphericity in every case of this series, with good clinical results and low morbidity. PMID- 26362041 TI - Change in acetabular version after lumbar pedicle subtraction osteotomy to correct post-operative flat back: EOS(r) measurements of 38 acetabula. AB - BACKGROUND: Abnormalities in acetabular orientation can promote the development of hip osteoarthritis, femoro-acetabular impingement, or even acetabular cup malposition. The objective of the present study was to determine whether pedicle substraction osteotomy (PSO) to correct sagittal spinal imbalance affected acetabular orientation. HYPOTHESIS: PSO performed to correct sagittal spinal imbalance affects acetabular orientation by changing the pelvic parameters. MATERIALS AND METHODS: This was a descriptive study in which two observers measured the acetabular parameters on both sides in 19 patients (38 acetabula) before and after PSO for post-operative flat-back syndrome. Mean time from PSO to post-operative measurements was 19months. Measurements were taken twice at a 2 week interval, on standing images obtained using the EOS((r)) imaging system and sterEOS((r)) software to obtain 3D reconstructions of synchronised 2D images. Acetabular anteversion and inclination were measured relative to the vertical plane. Mean pre-PSO and post-PSO values were compared using the paired t-test, and P values lower than 0.05 were considered significant. To assess inter observer and intra-observer reproducibility, we computed the intra-class correlation coefficients (ICCs). RESULTS: The measurements showed significant acetabular retroversion after PSO, of 7.6 degrees on the right and 6.5 degrees on the left (P<0.001). Acetabular inclination diminished significantly, by 4.5 degrees on the right and 2.5 degrees on the left (P<0.01). Inclination of the anterior pelvic plane decreased by 8.4 degrees (P<0.01). Pelvic incidence was unchanged, whereas sacral slope increased by 10.5 degrees (P<0.001) and pelvic tilt decreased by 10.9 degrees (P<0.001). The ICC was 0.98 for both inter observer and intra-observer reproducibility. CONCLUSION: Changing the sagittal spinal alignment modifies both the pelvic and the acetabular parameters. PSO significantly increases sacral slope, thus inducing anterior pelvic tilt with significant acetabular retroversion. The measurements obtained using sterEOS((r)) showed good inter-observer and intra-observer reproducibility. To our knowledge, this is the first study of changes in acetabular version after PSO. PMID- 26362042 TI - Meniscoplasty for lateral discoid meniscus tears: Long-term results of 14 cases. AB - INTRODUCTION: Discoid lateral meniscus lesions are relatively rare. The objective of this study was to determine the long-term results of 14 cases of discoid lateral meniscus tears treated by arthroscopic meniscoplasty between July 1991 and May 2009, and to assess the development of osteoarthritis in the lateral compartment. METHODS: The series consisted of 10 patients (14 knees): 3 girls under the age of 15, 3 men and 4 women aged from 16 to 47 years (mean age: 31.4+/ 11.1 years). The main reason for consultation was pain in 10 cases, locking in 2 cases and pain associated with locking in 2 cases. The diagnosis was confirmed preoperatively by MRI in 10 cases, CT-arthrography in 1 case and arthrography in 3 cases. The indication for surgery was made because of a symptomatic discoid lateral meniscus. All cases were treated by arthroscopic meniscal reshaping. Functional results were evaluated using the Lysholm-Tegner, IKDC, KOOS and satisfaction scores. Radiological results were evaluated based on the modified Alhback classification for osteoarthritic (OA) changes. RESULTS: No complications were found. Two patients were lost to follow-up. The remaining eight patients (12 knees) were reviewed at a mean of 157.5+/-72.1 months (61-276). The mean Lysholm Tegner score was 88.9+/-10.6 points (67-100), the mean KOOS was 92.4+/-9.5 (65 100) and the mean IKDC score was 85.4+/-16.5 points (65-100). All eight of the reviewed patients were satisfied or very satisfied with the result. Radiological analysis found that five knees had no signs of OA, five knees had stage 1, one had stage 2 and one had stage 3. At last follow-up, no patient had been reoperated. CONCLUSION: Meniscoplasty of discoid lateral meniscus tears leads to excellent long-term functional results despite signs of osteoarthritic changes in the lateral compartment of the knee. LEVEL OF EVIDENCE: IV (retrospective study). PMID- 26362043 TI - Does severity of femoral trochlear dysplasia affect outcome in patellofemoral instability treated by medial patellofemoral ligament reconstruction and anterior tibial tuberosity transfer? AB - INTRODUCTION: Medial patellofemoral ligament (MPFL) reconstruction associated to anterior tibial tuberosity transfer (ATTT) is recommended in objective patellofemoral instability (PFI). Efficacy, however, has not been precisely determined in trochlear dysplasia with spur. A case-control study was performed in a PFI population, comparing groups with trochlear dysplasia with and without spur (S+ vs. S-) to assess the impact of trochlear dysplasia on (1) patellofemoral stability, (2) functional results and complications, and (3) patellofemoral cartilage status on MRI. HYPOTHESIS: Trochlear spur does not affect outcome in PFI managed by MPFL reconstruction and ATTT. MATERIAL AND METHODS: Twenty-eight knees (26 patients) with PFI were analyzed retrospectively and divided into 2 groups of 14 knees each according to presence of trochlear spur (S+ vs. S-). All 28 knees had undergone ATTT and MPFL reconstruction by semitendinosus autograft. Results were assessed on Lille and IKDC functional scores, and cartilage status was determined on MRI at last follow-up. RESULTS: At a mean 24 months' follow-up (range, 12-52 months), there was no recurrence of dislocation. IKDC and Lille scores tended to improve in both groups, although the only significant improvement was in IKDC score (S- gain, 21.3+/-16; S+ gain, 18.1+/-14) (P=0.01). IKDC scores at last follow-up were better in the S+ than S- group (79+/-19 [range, 21-92] vs. 68+/-13 [range, 35-84], respectively; P=0.012). Lille scores showed no significant inter-group differences in mean gain (P=0.492) or mean value (P=0.381). The S+ group showed more cartilage lesions (n=14/14 knees, including 12/14 with grade>=2 lesions) than the S- group (n=9/14 knees, all grade<=2). CONCLUSION: MPFL reconstruction with ATTT provided good short-term patellofemoral stability independently of the severity of trochlear dysplasia. Functional results and gain on IKDC, however, were poorer in case of dysplasia with trochlear spur. This is probably due to cartilage lesions, observed more frequently pre- and post-operatively in the spur group, especially as there was no significant difference in Lille Score, which highlights stability. LEVEL OF EVIDENCE: III, retrospective case-control study. PMID- 26362044 TI - Conversion of total shoulder arthroplasty to reverse shoulder arthroplasty made possible by custom humeral adapter. AB - Reverse shoulder arthroplasty (RSA) is increasingly being used to revise anatomical total shoulder arthroplasty cases. This procedure's high complication rate has been reduced by the availability of modular shoulder systems, which allows the humeral component to be preserved during the conversion. This case report describes the revision of an anatomical shoulder implant inserted in 1998. Polyethylene wear and the resulting metal-on-metal contact had caused metallosis. Since the existing humeral implant was not compatible with standard conversion products, the manufacturer provided a custom humeral adapter that allowed the humeral stem to be preserved. This approach greatly simplified the surgical procedure and resulted in good anatomical and clinical outcomes after 9 months of follow-up. PMID- 26362045 TI - Pharmacodynamics (PD) and pharmacokinetics (PK) of E7389 (eribulin, halichondrin B analog) during a phase I trial in patients with advanced solid tumors: a California Cancer Consortium trial. AB - BACKGROUND: The California Cancer Consortium completed a phase I trial of E7389 (eribulin mesylate), an analog of the marine natural product halichondrin B. This trial was to determine the pharmacodynamics, pharmacokinetics, and MTD of E7389 administered by bolus injection weekly for 3 weeks out of four. METHODS: This trial included a rapid titration design. Real-time pharmacokinetics were utilized to guide dose escalation. Initially, single-patient cohorts were enrolled with intra- and inter-patient dose doubling. The second phase was a standard 3 + 3 dose escalation schedule. At the MTD, a cohort of patients was enrolled for target validation studies (separate manuscript). The starting dose was 0.125 mg/m(2), and doses were doubled within and between patients in the first phase. Blood and urine sampling for E7389 pharmacokinetics was performed on doses 1 and 3 of cycle 1. Levels were determined using a LC/MS/MS assay. RESULTS: Forty patients were entered. Thirty-eight were evaluable for toxicity and 35 for response. The rapid escalation ended with a grade 3 elevation of alkaline phosphatase at 0.5 mg/m(2)/week. The second phase ended at 2.0 mg/m(2)/week with dose-limiting toxicities of grades 3 and 4 febrile neutropenia. Other toxicities included hypoglycemia, hypophosphatemia, and fatigue. The MTD was 1.4 mg/m(2)/week. Responses included four partial responses (lung cancer [2], urothelial [1], and melanoma [1]). CONCLUSIONS: E7389 was well tolerated in this trial with the major toxicity being myelosuppression. PD shows that E7389 induces significant morphologic changes (bundle formation) in the microtubules of peripheral blood mononuclear cells and tumor cells in vivo. The data suggest that lower intra-tumoral levels of beta-tubulin III or higher intra-tumoral levels of MAP4 may correlate with response to E7389, while lower intra-tumoral levels of stathmin may be associated with progression. PK data reveal that E7389 exhibits a tri-exponential elimination from the plasma of patients receiving a rapid i.v. infusion. At sub-toxic doses, plasma concentrations of E7389 are maintained well above the levels required for activity in vitro for >72 h. PMID- 26362046 TI - Cognitive rehabilitation training in patients with brain tumor-related epilepsy and cognitive deficits: a pilot study. AB - The aim of this pilot observational study was to evaluate effect of cognitive rehabilitation training (RehabTr) on cognitive performances in patients with brain tumor-related epilepsy (BTRE) and cognitive disturbances. Medical inclusion criteria: patients (M/F) >= 18 years <= 75 with symptomatic seizures due to primary brain tumors or brain metastases in stable treatment with antiepileptic drugs; previous surgical resection or biopsy; >70 Karnofsky Performance Status; stable oncological disease. Eligible patients recruited from 100 consecutive patients with BTRE at first visit to our Center from 2011 to 2012. All recruited patients were administered battery of neuropsychological tests exploring various cognitive domains. Patients considered to have a neuropsychological deficit were those with at least one test score for a given domain indicative of impairment. Thirty patients out of 100 showed cognitive deficits, and were offered participation in RehabTr, of which 16 accepted (5 low grade glioma, 4 high grade glioma, 2 glioblastoma, 2 meningioma and 3 metastases) and 14 declined for various reasons. The RehabTr consisted of one weekly individual session of 1 h, for a total of 10 weeks, carried out by a trained psychologist. The functions trained were: memory, attention, visuo-spatial functions, language and reasoning by means of Training NeuroPsicologico (TNP((r))) software. To evaluate the effect of the RehabTr, the same battery of tests was administered directly after cognitive rehabilitation (T1), and at six-month follow-up (T2). Statistical analysis with Student T test for paired data showed that short-term verbal memory, episodic memory, fluency and long term visuo-spatial memory improved immediately after the T1 and remained stable at T2. At final follow-up all patients showed an improvement in at least one domain that had been lower than normal at baseline. Our results demonstrated a positive effect of rehabilitative training at different times, and, for these reasons, should encourage future research in this area with large, randomized clinical trials that evaluate the impact of a cognitive rehabilitation in patients with BTRE and cognitive deficits. PMID- 26362047 TI - Ion Mobility-Mass Spectrometry Reveals the Energetics of Intermediates that Guide Polyproline Folding. AB - Proline favors trans-configured peptide bonds in native proteins. Although cis/trans configurations vary for non-native and unstructured states, solvent also influences these preferences. Water induces the all-cis right-handed polyproline-I (PPI) helix of polyproline to fold into the all-trans left-handed polyproline-II (PPII) helix. Our recent work has shown that this occurs via a sequential mechanism involving six resolved intermediates [Shi, L., Holliday, A.E., Shi, H., Zhu, F., Ewing, M.A., Russell, D.H., Clemmer, D.E.: Characterizing intermediates along the transition from PPI to PPII using ion mobility-mass spectrometry. J. Am. Chem. Soc. 136, 12702-12711 (2014)]. Here, we use ion mobility-mass spectrometry to make the first detailed thermodynamic measurements of the folding intermediates, which inform us about how and why this transition occurs. It appears that early intermediates are energetically favorable because of the hydration of the peptide backbone, whereas late intermediates are enthalpically unfavorable. However, folding continues, as the entropy of the system increases upon successive formation of each new structure. When PPII is immersed in 1-propanol, the PPII->PPI transition occurs, but this reaction occurs through a very different mechanism. Early on, the PPII population splits onto multiple pathways that eventually converge through a late intermediate that continues on to the folded PPI helix. Nearly every step is endothermic. Folding results from a stepwise increase in the disorder of the system, allowing a wide scale search for a critical late intermediate. Overall, the data presented here allow us to establish the first experimentally determined energy surface for biopolymer folding as a function of solution environment. PMID- 26362048 TI - Substaging of Lymph Node Status in Resected Pancreatic Ductal Adenocarcinoma Has Strong Prognostic Correlations: Proposal for a Revised N Classification for TNM Staging. AB - BACKGROUND: The current tumor-node-metastasis staging system for the pancreas does not incorporate the number of lymph nodes (LNs) with metastasis. METHODS: Among 1649 pancreaticoduodenectomies, 227 stringently defined pancreatic ductal adenocarcinomas (PDACs) that had undergone a specific approach of LN harvesting were analyzed for the prognostic value of LN substaging protocols used for other gastrointestinal (GI) organs. RESULTS: The median number of LNs harvested was 18, and the median number of LNs with metastasis was 3. Lymph node metastasis was detected in 175 cases (77 %). The number of LNs involved correlated significantly with clinical outcome. When cases were substaged with the protocol already in use for the upper GI organs (N0: no metastasis, N1: metastasis to 1-2 LNs; N2: metastasis to >=3 LNs), the median overall survival times were 35, 21, and 18 months, and the respective 3-year survival rates were 46, 34, and 20 % (p = 0.004). Analysis of the Surveillance, Epidemiology and End Results (SEER) database also confirmed the survival differences between these substages (median overall survival times of 23, 15, and 14 months and respective 3-year survival rates of 37, 22, and 18 %; p < 0.0001). The substaging protocol for the lower GI organs (N0: no metastasis; N1: metastasis to 1-3 LNs; N2: metastasis to >=4 LNs) also was significant, with median overall survival times of 35, 21, 18 months and respective 3-year survival rates of 46, 26, and 23 %; p = 0.009). The association between higher N stage and shorter survival persisted with multivariate modeling for both protocols, although the prognostic value of the upper GI protocol appeared to be slightly stronger according to the Akaike Information Criterion method. CONCLUSION: In conclusion, with proper LN harvesting, the LN metastasis rate in PDACs is very high (77 %). Substaging of LN metastasis has significant prognostic value and needs to be considered in the N staging of PDACs. The protocol already in use for other upper GI tract organs, which currently also is proven significant for ampulla, would be preferable, although the lower GI tract protocol also is applicable. PMID- 26362049 TI - Psychiatric Illness is a Disparity in the Surgical Management of Rectal Cancer. AB - BACKGROUND: Psychiatric disorders are common in the US and represent a major health disparity but little is known about their impact on surgical management and outcomes in cancer. OBJECTIVE: The aim of this study was to determine whether rectal cancer patients with psychiatric diagnoses have fewer sphincter-preserving procedures and higher postoperative complications. METHODS: Overall, 23,914 patients from the Nationwide Inpatient Sample (NIS) who underwent surgery for rectal cancer from 2004 to 2011 were identified. Patients with comorbid common psychiatric diagnoses were identified by International Classification of Diseases, Ninth Revision (ICD-9) codes. Main outcomes were measured by operation performed, length of stay (LOS), postoperative complications, and discharge disposition. RESULTS: Twenty percent of patients had a psychiatric diagnosis, with substance use being the most common psychiatric disorder (63 %). Patients with psychiatric diagnoses were more likely to be younger, White, have lower income, and have Medicaid insurance (p < 0.001) than those without. In a logistic regression model, patients with any psychiatric diagnosis were less likely to have sphincter-sparing surgery, controlling for patient sociodemographics, Charlson score, hospital procedure volume, and year (odds ratio 0.77; 95 % CI 0.72-0.83). LOS and postoperative complications were similar among the cohorts. Patients with psychiatric disorders were more likely to have home health care at discharge (p < 0.001). CONCLUSIONS: Fewer sphincter-sparing procedures were performed on rectal cancer patients with psychiatric diagnoses. However, no significant differences in postoperative complications were observed. PMID- 26362050 TI - Role of amino acids as additives on sperm motility, plasma membrane integrity and lipid peroxidation levels at pre-freeze and post-thawed ram semen. AB - The possibility of including amino acids for cryopreservation of ram semen to improve the quality of frozen semen was explored in this study in sheep model. 24 samples were collected in triplicate from 8 rams of 2-3 year old Bannur cross bred rams maintained at the Institute Experimental Livestock Unit. Semen was diluted in tris-egg yolk glycerol diluent and made into 7 aliquots as follows: aliquot 1 served as control, "l-alanine" was added at 100 and 135mM in the aliquots 2 and 3, "l-glutamine" was added at 20 and 25mM in the aliquots 4 and 5 and "l-proline" was added at 25 and 50mM in the aliquots 6 and 7, respectively. Diluted semen was filled in 0.25ml French straws and frozen in LN2. Inclusion of "l-proline" and "l-glutamine" in the diluent increased the percent live sperm (P<0.001), total motility (P<0.05) and maintained higher functional membrane and acrosomal integrity (P<0.001) by decreasing lipid peroxidation (P<0.001) compared to the control group. In contrast, "l-alanine" decreased the percentage of total motility, fast progressive spermatozoa and increased (P<0.01) the percentage of immotile spermatozoa. It can be concluded that 20mM "l-glutamine" and 25mM "l proline" can be used as semen additive to freeze ram semen as they prevented cryoinjuries to sperm and improved the pre-freeze and post-thaw semen characteristics. PMID- 26362052 TI - Left ventricular outflow tract obstruction masked by severe aortic stenosis. AB - An 81-year-old woman developed severe hemolytic anemia after aortic valve replacement. The anemia was not caused by paravalvular leakage, as in most cases. Instead, it occurred secondary to left ventricular outflow tract obstruction that had not been seen preoperatively and was induced by afterload reduction following aortic valve replacement. The hemolytic anemia was drug-refractory and finally treated with dual-chamber pacing, as for hypertrophic cardiomyopathy. PMID- 26362051 TI - Trabecular metal spacers as standalone or with pedicle screw augmentation, in posterior lumbar interbody fusion: a prospective, randomized controlled trial. AB - PURPOSE: This prospective randomized comparative trial compared radiological and clinical outcome of Trabecular MetalTM (TM) spacers in PLIF, used as standalone (SA) devices, to TM spacers in PLIF with pedicle screw fixation (PF), in patients with single-level degenerative disc disease (DDD). METHODS: Patients (n = 80) with chronic low back pain and single-level degenerative disc were randomly assigned to the SA PLIF (n = 40) or PLIF with PF (n = 40). The primary radiological outcome was the evaluation of a long-term (+/-6 years; range 6.0-7.7 years) stable construct measured by dynamic X-rays. CT scan does not allow judging the bony bridging between vertebrae, because of Tantalum artefacts. The clinical evaluation (6 weeks, 6, 12 and 24 months) consisted of the Oswestry Disability Index (ODI) score, intensity of low back pain (Visual Analogue Scale) and quality of life (Short Form-36). RESULTS: At 6-year follow-up, X-rays showed a stable construct in 94 % of patients treated by SA TM-500 spacers and in 97 % of those with additional PF. Neither subsidence nor migration was observed in either the SA or the PF group. The average improvement in ODI scores at 24-month clinical follow-up was 14.4 and 13.8 for the SA and PF group, respectively. The VAS score showed an average improvement of 6.4 (SA) and 6.7 (PF), 2 years after implantation. No significant difference between groups was observed at all the evaluation points. CONCLUSION: In this study, TM spacers were found to provide a solid construct at more than 6-year follow-up after PLIF for DDD both with and without additional pedicle fixation. The clinical, but also radiological results were not significantly different between both cohorts. Future studies focusing on the differences of SA and PF at L4/5 level should be powered to study differences in post-surgery stability at the long term. PMID- 26362054 TI - [Mechanical support systems in the intensive care unit]. PMID- 26362057 TI - Undergraduate surgical nursing preparation and guided operating room experience: A quantitative analysis. AB - The aim of this research was to determine if guided operating theatre experience in the undergraduate nursing curricula enhanced surgical knowledge and understanding of nursing care provided outside this specialist area in the pre- and post-operative surgical wards. Using quantitative analyses, undergraduate nurses were knowledge tested on areas of pre- and post-operative surgical nursing in their final semester of study. As much learning occurs in nurses' first year of practice, participants were re-tested again after their Graduate Nurse Program/Preceptorship year. Participants' results were compared to the model of operating room education they had participated in to determine if there was a relationship between the type of theatre education they experienced (if any) and their knowledge of surgical ward nursing. Findings revealed undergraduates nurses receiving guided operating theatre experience had a 76% pass rate compared to 56% with non-guided or no experience (p < 0.001). Graduates with guided operating theatre experience as undergraduates or graduate nurses achieved a 100% pass rate compared to 53% with non-guided or no experience (p < 0.001). The research informs us that undergraduate nurses achieve greater learning about surgical ward nursing via guided operating room experience as opposed to surgical ward nursing experience alone. PMID- 26362059 TI - Twenty years of gastroenteropancreatic neuroendocrine tumors: is reclassification worthwhile and feasible? AB - Gastroenteropancreatic (GEP) neuroendocrine tumors (NETs) are rare neoplasms with heterogeneous clinical behavior and potential long-term survival. In 2006/2007, the European Neuroendocrine Tumors Society introduced an important parameter, grade (based on mitoses and Ki-67 proliferation rate), which became part of the latest 2010-WHO classification. Since this is an important tool in the choice of therapeutic algorithm of patients with NETs, our aim was to audit whether retrospective reclassification is possible and feasible and correlate pathological findings with survival. From the histopathology archive, 338 GEP NETs (1994-2014) were identified, of which 250 were diagnosed pre-2010 and 80 of these have needed, up till now, classification (morphology and grade-mitotic count/Ki-67). Morphology was well differentiated (WD) in 74 cases while only 6 cases were poorly differentiated (PD). Grade was reclassified: G1-45 cases (56 %); G2-28 cases (35 %); G3-7 cases (9 %). Overall survival (OS) in WD NETs was strikingly better compared to PD neoplasms. Differences in OS between grade were statistically significant (p < 0.0001) and, in particular, grade identified a subgroup of patients with WD lesions but with less favorable clinical behavior (OS at 5 years: G1-89 %; G2-48 %; G3-0 %; G1 vs G2 p = 0.03). Feasibility analysis quantified time for reclassification to be between 45 and 64 min/case. Our series confirms the importance of grade in prognostic stratification and underlines that reclassification is feasible, and may prove worthwhile in patient management, especially in view of the potential long survival of patients with NETs and risk of use of inappropriate therapies. PMID- 26362058 TI - Structural determination of virus protein U from HIV-1 by NMR in membrane environments. AB - Virus protein U (Vpu) from HIV-1, a small membrane protein composed of a transmembrane helical domain and two alpha-helices in an amphipathic cytoplasmic domain, down modulates several cellular proteins, including CD4, BST 2/CD317/tetherin, NTB-A, and CCR7. The interactions of Vpu with these proteins interfere with the immune system and enhance the release of newly synthesized virus particles. It is essential to characterize the structure and dynamics of Vpu in order to understand the mechanisms of the protein-protein interactions, and potentially to discover antiviral drugs. In this article, we describe investigations of the cytoplasmic domain of Vpu as well as full-length Vpu by NMR spectroscopy. These studies are complementary to earlier analysis of the transmembrane domain of Vpu. The results suggest that the two helices in the cytoplasmic domain form a U-shape. The length of the inter-helical loop in the cytoplasmic domain and the orientation of the third helix vary with the lipid composition, which demonstrate that the C-terminal helix is relatively flexible, providing accessibility for interaction partners. PMID- 26362061 TI - Assessment of the HPA Axis: Another New Test? PMID- 26362060 TI - Serum periostin is a potential biomarker for non-alcoholic fatty liver disease: a case-control study. AB - Recent animal studies support close associations of Periostin with hepatosteatosis and steatohepatitis. This study is to evaluate the role of serum periostin in non-alcoholic fatty liver disease (NAFLD). A hospital-based age-/sex matched case-control study was conducted. Binary logistic regression and receiver operating characteristic (ROC) curve were performed. Serum adipokines were measured by Adipokine Magnetic Bead Panel kits. The serum concentration of Periostin in NAFLD (1914.16 [1323.59-2654.88] ng/ml, P < 0.001) was higher than it in control (1244.94 [837.87-2028.55] ng/ml). The frequency of NAFLD grew (29.8, 52.6, and 67.2%, P < 0.001), as Periostin concentration increased among its tertiles. Compared with the 1st tertile, the 2nd and the 3rd tertiles of Periostin indicated significant associations with higher odds of NAFLD [adjusted odds ratio = 2.602 (95% confidence interval (CI) 1.030-6.575), P = 0.043 and 2.819 (95% CI 1.629-4.878), P < 0.001]. ROC curve of Periostin was developed to predict the presence of NAFLD (area under ROC = 0.693 [95% CI 0.614-0.771], P < 0.001). Lastly, Periostin correlated with several adipokines, including Resistin (r = 0.269, P = 0.018), Adiponectin (r = -0.352, P = 0.002), Interleukin (IL)-6 (r = 0.359, P = 0.001), IL-8 (r = 0.364, P = 0.001), Lipocalin-2 (r = 0.623, P < 0.001), Hepatocyte growth factor (r = 0.522, P < 0.001), and Nerve growth factor (r = 0.239, P = 0.036). It suggests Periostin as a potential biomarker in the management of NAFLD. PMID- 26362063 TI - Peliosis hepatis disseminated rapidly throughout the liver in a patient with prostate cancer: a case report. AB - INTRODUCTION: In the World Health Organization histological classification of the liver tumor, peliosis hepatis is defined as a tumor-like lesion. The entity is characterized by the appearance of multiple cyst-like, blood-filled spaces within the liver parenchyma. CASE PRESENTATION: A 77-year-old Japanese man with prostate cancer was referred to our department because he was diagnosed as having two hepatic tumors. The tumors were confirmed to be peliosis hepatis by repeated needle biopsies and because of their atypical images by enhanced computed tomography and enhanced magnetic resonance imaging. Later these tumors grew rapidly, increased in number, and disseminated throughout his whole liver. We are now treating the patient conservatively due to his age and his existing medical conditions. CONCLUSION: Peliosis hepatis is a rare hepatic benign tumor that should be considered in the differential diagnosis of multiple unknown liver tumors that are revealed by atypical radiological images. PMID- 26362064 TI - Pregnancy outcomes before and after institution of a specialised twins clinic: a retrospective cohort study. AB - BACKGROUND: Although specialised clinics for multiple pregnancies are recommended by several Obstetrics and Gynaecology governing bodies, studies examining outcome before and after introduction of such clinics remain few, were performed predominantly in North America in the 1990s, and either amongst dichorionic twin pregnancies only or where chorionicity was not specified. Our objective, in the modern setting with twins of known chorionicity, was to compare maternal and neonatal outcomes of twin pregnancies before and after commencement of a consultant-led, multidisciplinary twins clinic (TC). METHODS: Retrospective cohort study of 513 women, with birth of twins at >=20 weeks' gestation, January 2007 to November 2011, at a metropolitan tertiary maternity hospital, Sydney, Australia. Demographic, pregnancy, and outcome data were obtained from hospital databases. Women receiving TC care (2009-2011) were compared to those receiving general antenatal clinic (ANC) care (2007-2010) and private care (2009-2011). Other models of care were excluded. Main outcome measures were total maternal inpatient stay, mode of birth, gestational age at birth, and neonatal nursery admission. RESULTS: 286 women were included in the main analyses: 84 attended ANC, 101 TC, and 101 a private obstetrician. TC women had similar demographics to ANC women and were slightly younger than private patients. TC women had lower Caesarean section rates (55% vs. 70% ANC and 76% private, p = 0.008) and fewer late preterm (34 + 0-36 + 6 weeks) births, (26%TC vs. 44% ANC and 41% private, p < 0.001). Median maternal inpatient stay was shorter in TC than ANC (7 vs. 8 days, p = 0.009) and similar to private (7 days). Nursery admission rates were higher in private patients (67% vs. 49% ANC and 47% TC, p = 0.001) and average birthweight lower (2283 g vs. 2501 g ANC and 2496 g TC, p < 0.001). CONCLUSIONS: Within a single centre, maternal and neonatal twin pregnancy outcomes varied significantly by model of care. Introducing a specialised twins clinic in our setting decreased Caesarean section rates, late preterm birth, and inpatient stay compared to ANC. PMID- 26362062 TI - Activation of SAPK/JNK mediated the inhibition and reciprocal interaction of DNA methyltransferase 1 and EZH2 by ursolic acid in human lung cancer cells. AB - BACKGROUND: Ursolic acid (UA), a pentacyclic triterpenoid, is known to have anti tumor activity in various cancers including human non small cell lung cancer (NSCLC). However, the molecular mechanisms underlying the action of UA remain largely unknown. METHODS: Cell viability was measured by MTT assays. Apoptosis was analyzed with Annexin V-FITC/PI Apoptosis Detection Kit by Flow cytometry. Western blot analysis was performed to measure the phosphorylation and protein expression of stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), DNMT1 [DNA (cytosine-5)-methyltransferase 1], enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) and SP1. Exogenous expression of SP1 and DNMT1 was carried out by transient transfection assays. RESULTS: We showed that UA inhibited the growth and induced apoptosis of NSCLC cells in the dose- and time-dependent fashion. Furthermore, we found that UA induced phosphorylation of SAPK/JNK and suppressed the protein expression of DNMT1 and EZH2. The inhibitor of SAPK/JNK (SP600125) blocked the UA-reduced expression of DNMT1 and EZH2. In addition, UA suppressed the expression of SP1 protein. Conversely, overexpression of SP1 reversed the effect of UA on DNMT1 and EZH2 expression, and feedback attenuated UA-induced phosphorylation of SAPK/JNK. Moreover, exogenous expression of DNMT1 antagonized the effect of UA on SAPK/JNK signaling, EZH2 protein expression, and NSCLC cell growth. CONCLUSION: Our results show that UA inhibits growth of NSCLC cells through SAPK/JNK-mediated inhibition of SP1; this in turn results in inhibition the expression of DNMT1 and EZH2. Overexpression of DNMT1 diminishes UA-reduced EZH2 protein expression. The negative feedback regulation of SAPK/JNK signaling by SP1 and DNMT1, and the reciprocal interaction of EZH2 and DNMT1 contribute to the overall effects of UA. This study leads to important new insights into the mechanisms by which UA controls growth of NSCLC cells. PMID- 26362066 TI - Intracranial Stenting Gets a Revisit but Outcomes Still Favor Medical Management. PMID- 26362065 TI - Effect of hydroalcoholic leaves extract of Indigofera spicata Forssk. on blood glucose level of normal, glucose loaded and diabetic rodents. AB - BACKGROUND: Diabetes mellitus is found in all parts of the world and is rapidly increasing in its coverage with alarming rate especially in Asia and Africa. Research is increasingly done with the aim of developing a relatively safe and efficacious anti-diabetic plant based products. Parallelly, this investigation was carried out to evaluate the effect of the hydro alcoholic leaves crude extract of Indigofera spicata (ISP) on the blood glucose level(BGL) of normoglycemic, oral glucose loaded and alloxan induced diabetic rodents. METHODS: The animals were randomly divided into five groups (n = 6) for all the aforementioned three models. In all models, group-I mice provided 2%tween-80, group-II were treated with 5 mg/kg glibenclamide and the remaining three groups (III, IV & V) were treated with 100, 200, and 400 mg/kg dose of the extract respectively. Statistical significance of differences in BGLs within and between groups was analyzed by SPSS version-21 using one way ANOVA followed by Tukey's post hoc multiple comparison. RESULT: 200 mg/kg and 400 mg/kg extract treated groups of normoglycemic mice showed significant (p < 0.05) BGL reduction compared to the pre-exposure level. In case of OGTT model BGL reduction was statistically significant (p < 0.05) in only 400 mg/kg exposed groups at the 120 min of post exposure compared to the initial level. However, the BGL reducing effect of doses of the extract at the 4(th), 6(th) and 10(th) hours of post treatment on diabetic mice was found statistically significant compared to both the negative control (p < 0.001) and their respective pretreatment levels (p < 0.05). CONCLUSION: As it is claimed in ethnobotanical studies, the hydroalcoholic crude extract of ISP leaves have shown prominent anti-diabetic effect and can be therefore used as a good insight for new anti-diabetic drug source with a call for further studies. PMID- 26362067 TI - Increased apoptosis, altered oxygen signaling, and antioxidant defenses in first trimester pregnancies with high-resistance uterine artery blood flow. AB - The mechanisms of deficient placentation in the first trimester remain poorly understood, although apoptosis, hypoxia, and oxidative stress have been implicated. High uterine artery Doppler resistance indexes (RIs) are predictive of placental complications of pregnancy, such as preeclampsia, fetal growth restriction, and stillbirth. We provide evidence that even in the first trimester, pregnancies with high uterine artery Doppler RI demonstrate alterations in placental gene and protein expression. Apoptosis was significantly higher in high RI placental tissue, as determined by Western blot analysis of cleaved poly (ADP-ribose) polymerase and caspase 3. Protein expression of the trophoblast survival factor insulin-like growth factor-2 was significantly lower. Both high and normal RI placentas showed evidence of hypoxia and oxidative stress with expression of hypoxia-inducible factors 1alpha and 2alpha, heat shock protein 70, presence of nitrotyrosine residues, and lipid peroxidation. We observed no exaggerated placental hypoxia or oxidative stress associated with high RI pregnancies. High RI placental tissue demonstrated an altered balance of antioxidant enzyme activity. Hypoxia and oxidative stress appear to be a physiological state in early pregnancy; our data did not support the hypothesis that they are associated with deficient placentation in the first trimester. Higher levels of apoptosis, reduced insulin-like growth factor-2 expression, and altered antioxidant defenses may contribute to abnormal placentation and the later development of pregnancy complications, such as preeclampsia, fetal growth restriction, and stillbirth. PMID- 26362068 TI - Growing gratitude in undergraduate nursing students: Applying findings from social and psychological domains to nursing education. AB - Millennial students are often characterized as technology focused multitaskers, yet young nursing students are expected to focus on and thoughtfully engage with the person at the center of their caring efforts. Developing gratitude practices requires quiet contemplation and focus. Cultivating an attitude of gratitude in millennial nursing students may be one avenue to address concerns surrounding the provision of relationship based person-centered care by young nurses. In other disciplines, gratitude work has been studied extensively and is associated with several positive outcomes. Assignments included in most nursing programs can easily be modified to include a gratitude focus. Examples of gratitude assignments and the student reflection of these assignments are included here as a call for nurse educators to further study this concept. PMID- 26362069 TI - Development of a simulation-based assessment to evaluate the clinical competencies of Korean nursing students. AB - OBJECTIVES: To describe a simulation-based assessment (SBA) to evaluate the clinical competencies of nursing students in children's health and to compare its results with grade point average (GPA), self-efficacy, topic-specific knowledge, and self-reported clinical competency using the Six-D Scale. METHODS: This cross sectional, descriptive study recruited nursing students from a children's health clinical practicum. Students were assigned to either an asthma (n=55) or a type 1 diabetes (n=48) care scenario conducted on a high-fidelity simulator. Clinical competencies were assessed using the global rating scale (GRS) and a checklist. RESULTS: Data on 103 students were analyzed. The SBA-GRS indicated that 64.6% 87.3% of students passed. The SBA-GRS showed a statistically significant positive association with the SBA checklist in both the asthma (rho=.763, p<.001) and the type 1 diabetes (rho=.475, p=.001) group. In the asthma group, the SBA-GRS and checklist showed statistically significant associations with GPA (rho=.413, p=.002 vs. r=.508, p<.001) and the Six-D Scale (rho=.266, p=.049 vs. r=.352, p=.008); in the diabetes group, only the SBA checklist showed a statistically significant association with self-efficacy (r=.339, p=.018) and the Six-D Scale (r=.373, p=.009). Four groups by SBA-GRS had statistically significant differences in scores on the SBA checklist in both groups (F=25.757, p<.001 in the asthma group; F=4.790, p=.006 in the diabetes group) and GPA only in the asthma groups (F=6.095, p<.001). CONCLUSION: SBA was found to be feasible for nursing students. The GRS and checklist were reasonably correlated with other evaluation methods of student competency, but correlations were better with easier scenarios. PMID- 26362070 TI - Eight cases of salvage pulmonary resection for residual disease or isolated local recurrence detected after definitive chemoradiotherapy for N2 Stage-IIIA lung cancer. AB - BACKGROUND/OBJECTIVE: The concept of salvage pulmonary resection after definitive chemoradiotherapy (dCRT) is not yet commonly accepted in lung cancer treatment. We report our experience of eight patients in whom we performed salvage pulmonary resection for residual disease or isolated locoregional recurrence detected after dCRT. METHODS: Between 2005 and 2014, we performed salvage pulmonary resection for eight patients with N2 Stage-IIIA non-small cell lung cancer. The patients had initially received dCRT (radiation <= 60 Gy), but eventually underwent pulmonary resection with curative intent for residual disease or isolated locoregional recurrence. The postoperative complications, incidence of recurrence, and survival parameters were evaluated. RESULTS: Salvage pulmonary resection was performed in four patients with residual disease and four patients with locoregional recurrence. Complete resection was successfully performed in all eight patients. Postoperative complications were observed in three patients, however, there were no postoperative mortalities. One patient developed local recurrence in a mediastinal lymph node and two patients died. Of the two fatalities, one was related to lung cancer. The estimated 5-year survival rate of the eight patients was 75.0%. CONCLUSION: We report our experience of salvage pulmonary resection performed for residual disease or isolated locoregional recurrence diagnosed after dCRT in eight patients with locally advanced lung cancer. Although the postoperative complication rate was high, the survival data were favorable. A larger study is needed to confirm the safety and feasibility of salvage pulmonary resection after dCRT. PMID- 26362071 TI - Acquired Type II von Willebrand Syndrome in Locally Advanced Bladder Cancer Successfully Treated With Intravenous Immunoglobulin and Chemotherapy. PMID- 26362072 TI - Comparison of Perioperative Morbidity of Radical Cystectomy With Neobladder Versus Ileal Conduit: A Matched Pair Analysis of 170 Patients. AB - BACKGROUND: The objective of this study was to evaluate if use of an ileal conduit (IC) versus a neobladder (NB) during radical cystectomy (RC) can play a role in the morbidity of the surgical procedure. PATIENTS AND METHODS: Since 2001 our institution has prospectively maintained a database of more than 500 patients who have undergone RC. The records of 258 patients who received an RC and IC and 121 who received an RC and NB were reviewed for the present study. Using a binary logistic regression model a propensity score was generated for the following factors: sex, age, smoking habit, Charlson score, American Society of Anesthesiology score, preoperative hydronephrosis, and pathologic T stage. Two groups of patients with similar propensity scores were created with a ratio of 1:1, one group who received an IC and another who received an NB. The following features were compared between the 2 groups: blood loss, intraoperative complication rate, time to oral intake resumption, postoperative complication rate (overall, Clavien classification 1-2, Clavien classification 3-5, related to RC, related to urinary reconstruction). RESULTS: In total, 170 patients were selected; 85 with NB, 85 with IC, and the 2 groups were well matched according to the desired features. No differences were noted for all of the compared features. CONCLUSION: The morbidity of RC does not seem to be affected by the choice of IC versus NB. PMID- 26362073 TI - Panitumumab Treatment for Advanced Penile Squamous Cell Carcinoma When Surgery and Chemotherapy Have Failed. AB - BACKGROUND: Patients with metastatic penile squamous cell carcinoma (SCC) have a poor prognosis and treatment options are needed when chemotherapy treatment fails. We present the final results of panitumumab treatment from our original series. PATIENTS AND METHODS: Eligibility included patients with unresectable or metastatic penile SCC, Eastern Cooperative Oncology Group performance status of 0 to 2, and failure of at least 1 chemotherapy regimen. Patients received panitumumab 6.0 mg/kg every 2 weeks until disease progression or unacceptable toxicity. Response was assessed by clinical examination or Response Evaluation Criteria in Solid Tumors version 1.1 criteria every 6 weeks, when applicable. Descriptive statistics were calculated and univariable Cox proportional hazards regression analysis was conducted. RESULTS: Between October 2010 and July 2013, 11 patients were treated. After a median of 5 panitumumab administrations (range, 1-11), we recorded 1 case of Grade 3 cutaneous toxicity and diarrhea each, and 2 cases of Grade 3 mucositis. One patient discontinued treatment because of skin toxicity. Two patients had a complete remission of skin nodules and of skin and nodal metastases, respectively. One patient had a partial regression of skin metastases, and 2 patients stable disease (clinical benefit: 45.5%). Median progression-free survival was 1.9 months (interquartile range [IQR], 0.9-3.0 months) and median overall survival (OS) was 9.5 months (IQR, 4.9-12.6). The presence of visceral metastases showed a trend for association with worse OS (P = .098). CONCLUSION: Panitumumab was active and safe in patients with highly pretreated penile SCC. The design of combination or sequential strategies with chemotherapy and in an earlier disease stage is warranted. PMID- 26362074 TI - Machine learning approaches to analyze histological images of tissues from radical prostatectomies. AB - Computerized evaluation of histological preparations of prostate tissues involves identification of tissue components such as stroma (ST), benign/normal epithelium (BN) and prostate cancer (PCa). Image classification approaches have been developed to identify and classify glandular regions in digital images of prostate tissues; however their success has been limited by difficulties in cellular segmentation and tissue heterogeneity. We hypothesized that utilizing image pixels to generate intensity histograms of hematoxylin (H) and eosin (E) stains deconvoluted from H&E images numerically captures the architectural difference between glands and stroma. In addition, we postulated that joint histograms of local binary patterns and local variance (LBPxVAR) can be used as sensitive textural features to differentiate benign/normal tissue from cancer. Here we utilized a machine learning approach comprising of a support vector machine (SVM) followed by a random forest (RF) classifier to digitally stratify prostate tissue into ST, BN and PCa areas. Two pathologists manually annotated 210 images of low- and high-grade tumors from slides that were selected from 20 radical prostatectomies and digitized at high-resolution. The 210 images were split into the training (n=19) and test (n=191) sets. Local intensity histograms of H and E were used to train a SVM classifier to separate ST from epithelium (BN+PCa). The performance of SVM prediction was evaluated by measuring the accuracy of delineating epithelial areas. The Jaccard J=59.5 +/- 14.6 and Rand Ri=62.0 +/- 7.5 indices reported a significantly better prediction when compared to a reference method (Chen et al., Clinical Proteomics 2013, 10:18) based on the averaged values from the test set. To distinguish BN from PCa we trained a RF classifier with LBPxVAR and local intensity histograms and obtained separate performance values for BN and PCa: JBN=35.2 +/- 24.9, OBN=49.6 +/- 32, JPCa=49.5 +/- 18.5, OPCa=72.7 +/- 14.8 and Ri=60.6 +/- 7.6 in the test set. Our pixel-based classification does not rely on the detection of lumens, which is prone to errors and has limitations in high-grade cancers and has the potential to aid in clinical studies in which the quantification of tumor content is necessary to prognosticate the course of the disease. The image data set with ground truth annotation is available for public use to stimulate further research in this area. PMID- 26362075 TI - Fractal texture analysis of the healing process after bone loss. AB - Radiological assessment of treatment effectiveness of guided bone regeneration (GBR) method in postresectal and postcystal bone loss cases, observed for one year. Group of 25 patients (17 females and 8 males) who underwent root resection with cystectomy were evaluated. The following combination therapy of intraosseous deficits was used, consisting of bone augmentation with xenogenic material together with covering regenerative membranes and tight wound closure. The bone regeneration process was estimated, comparing the images taken on the day of the surgery and 12 months later, by means of Kodak RVG 6100 digital radiography set. The interpretation of the radiovisiographic image depends on the evaluation ability of the eye looking at it, which leaves a large margin of uncertainty. So, several texture analysis techniques were developed and used sequentially on the radiographic image. For each method, the results were the mean from the 25 images. These methods compute the fractal dimension (D), each one having its own theoretic basis. We used five techniques for calculating fractal dimension: power spectral density method, triangular prism surface area method, blanket method, intensity difference scaling method and variogram analysis. Our study showed a decrease of fractal dimension during the healing process after bone loss. We also found evidence that various methods of calculating fractal dimension give different results. During the healing process after bone loss, the surfaces of radiographic images became smooth. The result obtained show that our findings may be of great importance for diagnostic purpose. PMID- 26362076 TI - [Lower urinary tract dysfunction following radical hysterectomy]. AB - INTRODUCTION: Radical hysterectomy is associated with a significant amount of urinary functional complications and a negative impact on quality of life. The aim of this review is to provide a comprehensive overview of the neurological etiology of lower urinary tract dysfunction following radical hysterectomy and to establish an optimal postoperative management strategy. MATERIAL AND METHODS: We performed a comprehensive overview using the following terms: "radical hysterectomy" and "urologic diseases etiology" or "urologic disease prevention and control". RESULTS: The reported incidence of lower urinary tract dysfunction after radical hysterectomy varies from 12 to 85%. Several animal and clinical urodynamic studies corroborate the neurologic etiology of the dysfunction. Lower urinary tract dysfunction is a common postoperative finding (70-85%) but spontaneous recovery is to be expected within 6-12 months after surgery. The most frequent long term sequela is stress urinary incontinence (40% of cases) and its management is complex and challenging. Postoperative refractory overactive bladder and bladder underactivity can be treated by neuromodulation of sacral roots and superior hypogastric plexus, respectively. In the absence of good clinical predictors, preoperative urodynamic examinations could have a role in understanding the pathophysiology of the dysfunction before such interventions. CONCLUSION: The pathophysiology of lower urinary tract dysfunction following radical hysterectomy is multifactorial. Its management is complex and should be multidisciplinary. PMID- 26362077 TI - The REC domain mediated dimerization is critical for FleQ from Pseudomonas aeruginosa to function as a c-di-GMP receptor and flagella gene regulator. AB - FleQ is an AAA+ ATPase enhancer-binding protein that regulates both flagella and biofilm formation in the opportunistic pathogen Pseudomonas aeruginosa. FleQ belongs to the NtrC subfamily of response regulators, but lacks the corresponding aspartic acid for phosphorylation in the REC domain (FleQ(R), also named FleQ domain). Here, we show that the atypical REC domain of FleQ is essential for the function of FleQ. Crystal structure of FleQ(R) at 2.3A reveals that the structure of FleQ(R) is significantly different from the REC domain of NtrC1 which regulates gene expression in a phosphorylation dependent manner. FleQ(R) forms a novel active dimer (transverse dimer), and mediates the dimerization of full length FleQ in an unusual manner. Point mutations that affect the dimerization of FleQ lead to loss of function of the protein. Moreover, a c-di-GMP binding site deviating from the previous reported one is identified through structure analysis and point mutations. PMID- 26362078 TI - Bone critical defect repair with poloxamine-cyclodextrin supramolecular gels. AB - The aim of this study was to evaluate the osteoinductive capacity of a poloxamine (Tetronic((r)) 908, T) and alpha-cyclodextrin (alphaCD) supramolecular gel (T-CD) as scaffold in a critical size defect in rat calvaria. The T-CD gel was evaluated solely and after being loaded with simvastatin (SV) and bone morphogenetic protein (BMP-2) separately and in combinations in order to reduce the doses of the active substances. Three doses of SV (7.5, 75, 750 MUg) and two doses of BMP 2 (3 and 6 MUg) were tested. The histology and histomorphometrical analysis showed improved bone repair with T-CD compared to T, probably due to better release control of both SV and BMP-2. In addition, as T-CD eroded more slowly than poloxamine alone, it remained longer in the defect site. Although synergism was not obtained with BMP-2 and SV, according to the observed regeneration of the defect, the dose of BMP-2 and SV can be reduced to 3 MUg and 7.5 MUg, respectively. PMID- 26362080 TI - Charging L500 for work experience in hospital is "completely unfair," says charity. PMID- 26362079 TI - The Contribution of Beverages to Intakes of Energy and MyPlate Components by Current, Former, and Never Smokers in the United States. AB - BACKGROUND: Although beverage intake patterns have been shown to differ by smoking status, it is unknown whether the contributions of beverages to intakes of energy and MyPlate components also differ. OBJECTIVE: The purpose of this study was to compare beverage intakes and contributions of energy and MyPlate components by source (food alone, beverages alone, and food and beverages together) in diets of adult current, former, and never smokers. DESIGN AND PARTICIPANTS: Dietary data from 4,823 men and 4,672 women aged >=20 years who participated in What We Eat in America, National Health and Nutrition Examination Survey 2005-2008, were analyzed. MAIN OUTCOME MEASURES: Beverage intake and the contributions to energy and MyPlate components by beverages. STATISTICAL ANALYSIS: Regression analyses identified differences in intake among groups. RESULTS: Current smokers consumed more total beverages, coffee, and sugar sweetened beverages than never and former smokers (P<0.001). Male current smokers drank more alcoholic beverages than never and former smokers, whereas female current and former smokers both consumed more alcoholic beverages than never smokers. Current smokers obtained more energy from beverages than their nonsmoking counterparts, although total energy intake did not differ. Intakes of added sugars, alcohol, and empty calories were higher for current than never smokers, and differences were accounted for by current smokers' beverage choices. CONCLUSIONS: This study adds to the body of research on smoking and dietary behavior by showing that not only do smokers consume a higher volume of beverages, but they also have a higher intake of energy provided by beverages, mainly empty calories from added sugars and alcohol. Our findings highlight the importance of assessing beverages' contribution to the total diet. Recognizing the common co-occurrence of smoking and specific beverage choices can help target health promotion and disease prevention efforts for this subpopulation. PMID- 26362081 TI - Risk assessment strategies for nanoscale and fine-sized titanium dioxide particles: Recognizing hazard and exposure issues. AB - The basic tenets for assessing health risks posed by nanoparticles (NP) requires documentation of hazards and the corresponding exposures that may occur. Accordingly, this review describes the range and types of potential human exposures that may result from interactions with titanium dioxide (TiO2) particles or NP - either in the occupational/workplace environment, or in consumer products, including food materials and cosmetics. Each of those applications has a predominant route of exposure. Very little is known about the human impact potential from environmental exposures to NP - thus this particular issue will not be discussed further. In the workplace or occupational setting inhalation exposure predominates. Experimental toxicity studies demonstrate low hazards in particle-exposed rats. Only at chronic overload exposures do rats develop forms of lung pathology. These findings are not supported by multiple epidemiology studies in heavily-exposed TiO2 workers which demonstrate a lack of correlation between chronic particle exposures and adverse health outcomes including lung cancer and noncancerous chronic respiratory effects. Cosmetics and sunscreens represent the major application of dermal exposures to TiO2 particles. Experimental dermal studies indicate a lack of penetration of particles beyond the epidermis with no consequent health risks. Oral exposures to ingested TiO2 particles in food occur via passage through the gastrointestinal tract (GIT), with studies indicating negligible uptake of particles into the bloodstream of humans or rats with subsequent excretion through the feces. In addition, standardized guideline-mandated subchronic oral toxicity studies in rats demonstrate very low toxicity effects with NOAELs of >1000 mg/kg bw/day. Additional issues which are summarized in detail in this review are: 1) Methodologies for implementing the Nano Risk Framework - a process for ensuring the responsible development of products containing nanoscale materials; and 2) Safe-handling of nanomaterials in the laboratory. PMID- 26362083 TI - People who believe body weight is genetic eat less healthily and take less exercise, study finds. PMID- 26362084 TI - Arteriovenous malformation embocure score (AVMES): response. PMID- 26362082 TI - Comparative Genomics of a Plant-Parasitic Nematode Endosymbiont Suggest a Role in Nutritional Symbiosis. AB - Bacterial mutualists can modulate the biochemical capacity of animals. Highly coevolved nutritional mutualists do this by synthesizing nutrients missing from the host's diet. Genomics tools have advanced the study of these partnerships. Here we examined the endosymbiont Xiphinematobacter (phylum Verrucomicrobia) from the dagger nematode Xiphinema americanum, a migratory ectoparasite of numerous crops that also vectors nepovirus. Previously, this endosymbiont was identified in the gut, ovaries, and eggs, but its role was unknown. We explored the potential role of this symbiont using fluorescence in situ hybridization, genome sequencing, and comparative functional genomics. We report the first genome of an intracellular Verrucomicrobium and the first exclusively intracellular non Wolbachia nematode symbiont. Results revealed that Xiphinematobacter had a small 0.916-Mb genome with only 817 predicted proteins, resembling genomes of other mutualist endosymbionts. Compared with free-living relatives, conserved proteins were shorter on average, and there was large-scale loss of regulatory pathways. Despite massive gene loss, more genes were retained for biosynthesis of amino acids predicted to be essential to the host. Gene ontology enrichment tests showed enrichment for biosynthesis of arginine, histidine, and aromatic amino acids, as well as thiamine and coenzyme A, diverging from the profiles of relatives Akkermansia muciniphilia (in the human colon), Methylacidiphilum infernorum, and the mutualist Wolbachia from filarial nematodes. Together, these features and the location in the gut suggest that Xiphinematobacter functions as a nutritional mutualist, supplementing essential nutrients that are depleted in the nematode diet. This pattern points to evolutionary convergence with endosymbionts found in sap-feeding insects. PMID- 26362085 TI - Interest of convex spherical anamorphosis in better understanding of brain AVMs' angioarchitecture. AB - INTRODUCTION: Convex spherical anamorphosis is a barrel distortion that consists of the application of a plane surface on a convex hemisphere. Applied in vascular imaging of brain arteriovenous malformations (bAVMs), this deformation may help to 'spread' the nidus and surrounding vessels (arteries/veins) and thus to differentiate the different components of bAVMs more accurately. METHODS: The imaging data from 15 patients (8 male, 7 female; 14 supratentorial bAVMs, 1 infratentorial) were used to test the algorithm. The algorithm was applied to three-dimensional rotational angiography (3D-RA) volume rendering reconstructions in anteroposterior, lateral and oblique views and compared with regular 3D-RA and DSA. Arterial feeder and draining vein count and quality visualization of the main draining vein and intranidal aneurysms were compared between the three imaging techniques. RESULTS: Anamorphosis was able to depict more arterial feeders than 3D-RA alone (p=0.027). There was no statistically significant difference between 6 f/s DSA and anamorphosis for arterial feeder count. No difference was observed in draining vein count between the three imaging modalities. Visualization of the precise origin of the main draining vein was considered to be good in 67% of the cases with anamorphosis versus 47% and 33% for 6 f/s DSA and 3D-RA alone, respectively. Intranidal aneurysms were accurately depicted by anamorphosis (2 cases), whereas 6 f/s DSA and 3D-RA showed doubtful images in one and two additional cases, respectively, which were finally confirmed as focal venous ectasias on supraselective injection. CONCLUSIONS: Anamorphosis can help to visualize more precisely the main draining vein origin of the bAVM and depict more accurately intranidal aneurysms. PMID- 26362086 TI - Hospital managers' need for information in decision-making--An interview study in nine European countries. AB - Assessments of new health technologies in Europe are often made at the hospital level. However, the guidelines for health technology assessment (HTA), e.g. the EUnetHTA Core Model, are produced by national HTA organizations and focus on decision-making at the national level. This paper describes the results of an interview study with European hospital managers about their need for information when deciding about investments in new treatments. The study is part of the AdHopHTA project. Face-to-face, structured interviews were conducted with 53 hospital managers from nine European countries. The hospital managers identified the clinical, economic, safety and organizational aspects of new treatments as being the most relevant for decision-making. With regard to economic aspects, the hospital managers typically had a narrower focus on budget impact and reimbursement. In addition to the information included in traditional HTAs, hospital managers sometimes needed information on the political and strategic aspects of new treatments, in particular the relationship between the treatment and the strategic goals of the hospital. If further studies are able to verify our results, guidelines for hospital-based HTA should be altered to reflect the information needs of hospital managers when deciding about investments in new treatments. PMID- 26362087 TI - Rescue Retrieval of a Fully Deployed Low-Profile Intracranial Stent After Acute Occlusion. AB - The use of self-expandable stents for endovascular treatment of intracranial aneurysms has increased over time. Different types of stent malpositioning, such as stent migration, distortion, incomplete opening, and apposition, can occur as a complication of the stent deployment procedure. In this report, we present a successful retrieval of a low-profile stent after full deployment in a dissecting posterior-inferior cerebellar artery because of incomplete apposition and subsequent acute occlusion of the stent. PMID- 26362088 TI - Small acid-soluble spore proteins of Clostridium acetobutylicum are able to protect DNA in vitro and are specifically cleaved by germination protease GPR and spore protease YyaC. AB - Small acid-soluble proteins (SASPs) play an important role in protection of DNA in dormant bacterial endospores against damage by heat, UV radiation or enzymic degradation. In the genome of the strict anaerobe Clostridium acetobutylicum, five genes encoding SASPs have been annotated and here a further sixth candidate is suggested. The ssp genes are expressed in parallel dependent upon Spo0A, a master regulator of sporulation. Analysis of the transcription start points revealed a sigmaG or a sigmaF consensus promoter upstream of each ssp gene, confirming a forespore-specific gene expression. SASPs were termed SspA (Cac2365), SspB (Cac1522), SspD (Cac1620), SspF (Cac2372), SspH (Cac1663) and Tlp (Cac1487). Here it is shown that with the exception of Tlp, every purified recombinant SASP is able to bind DNA in vitro thereby protecting it against enzymic degradation by DNase I. Moreover, SspB and SspD were specifically cleaved by the two germination-specific proteases GPR (Cac1275) and YyaC (Cac2857), which were overexpressed in Escherichia coli and activated by an autocleavage reaction. Thus, for the first time to our knowledge, GPR-like activity and SASP specificity could be demonstrated for a YyaC-like protein. Collectively, the results assign SspA, SspB, SspD, SspF and SspH of C. acetobutylicum as members of alpha/beta type SASPs, whereas Tlp seems to be a non-DNA-binding spore protein of unknown function. In acetic acid-extracted proteins of dormant spores of C. acetobutylicum, SspA was identified almost exclusively, indicating its dominant biological role as a major alpha/beta-type SASP in vivo. PMID- 26362089 TI - Differential alterations of tissue T-cell subsets after sepsis. AB - Among immune cells in responding to sepsis, macrophages and neutrophils have been extensively studied, while the contribution of T lymphocytes and natural killer T (NKT) cells is less well characterized. Here we monitored tissue specific changes of T cell subsets in male C57BL/6 mice subjected to sham operation or cecal ligation and puncture (CLP) to induce polymicrobial sepsis. Thymus, spleen, liver, lungs and blood were processed and analyzed 20h later. Total lymphocyte count showed a significant reduction in septic thymus, spleen and blood but not in lungs and liver. The septic thymi were hypocellular with severe reduction in cell numbers of immature CD4(+)CD8(+) subset. CD4(+) T and CD8(+) T lymphocyte numbers in septic spleens were also significantly reduced, but the frequency of CD4(+)CD25(+) Tregs was significantly increased. In addition, naive and Tcm CD4(+) T cell numbers were significantly reduced in the septic spleens. By contrast, in septic liver the CD8(+) T cell numbers were significantly increased, whereas NKT cell numbers were reduced, but more activated with increased CD69 and CD25 expression. In the septic lungs, the CD4(+) T and CD8(+) T cell numbers showed no significant change, whereas they were severely reduced in the septic blood. Overall, this study provides important information on the alterations of different T-cell subsets in various tissues after sepsis. PMID- 26362091 TI - Reply to Wentao Liu, Xiaokun Zhao, Zhaohui Zhong's Letter to the Editor re: Marcus G. Cumberbatch, Matteo Rota, James W.F. Catto, Carlo La Vecchia. The Role of Tobacco Smoke in Bladder and Kidney Carcinogenesis: A Comparison of Exposures and Meta-analysis of Incidence and Mortality Risks. Eur Urol 2016;70:458-66. PMID- 26362090 TI - Cardiovascular Mortality Following Short-term Androgen Deprivation in Clinically Localized Prostate Cancer: An Analysis of RTOG 94-08. AB - BACKGROUND: Androgen deprivation therapy (ADT) is associated with coronary heart disease and diabetes in men with prostate cancer (PCa); however, controversy exists regarding ADT and cardiovascular mortality (CVM) with limited data for lower risk disease. OBJECTIVE: We conducted a hypothesis-generating retrospective analysis to evaluate the relationship between short-course ADT and CVM in patients with clinically localized PCa enrolled in a phase III trial. DESIGN, SETTING, AND PARTICIPANTS: A total of 1979 men with clinically localized (T1b-2b, prostate-specific antigen [PSA] <20 ng/ml) PCa enrolled in Radiation Therapy Oncology Group (RTOG) 94-08 from 1994 to 2001. Patients were randomized to radiation therapy (RT) with or without short-course ADT (4 mo of gonadotropin releasing hormone (GnRH) agonist therapy and antiandrogen). Median follow-up was 9.1 yr for survivors. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The Cox proportional hazards model assessed overall survival. The Fine-Gray proportional hazards model assessed disease-specific survival (DSS) and CVM. Covariates included age, race, weight, baseline cardiovascular disease, baseline diabetes, baseline hypertension, Gleason score, T stage, and PSA. RESULTS AND LIMITATIONS: Short-course ADT improved overall survival and DSS and was not associated with an increased risk of CVM. Overall, 191 cardiovascular-related deaths were observed. At 10 yr, 83 patients (cumulative incidence rate: 10%) receiving RT and ADT versus 95 patients (cumulative incidence rate: 11%) receiving RT alone experienced CVM. The treatment arm was not associated with increased CVM (unadjusted hazard ratio: 1.07; confidence interval, 0.81-1.42; p=0.62). Increased CVM was not observed in patients at low risk of PCa death or at high risk of cardiac-related death. CONCLUSIONS: Data from patients enrolled in RTOG 94-08 support the hypothesis that ADT does not increase CVM risk in men with clinically localized PCa treated with short-course GnRH agonist therapy. These data support ADT use in settings with proven survival benefit. PATIENT SUMMARY: We investigated the controversial relationship between hormone therapy and cardiovascular mortality in men with prostate cancer (PCa) treated with radiation in a large randomized trial. Our data suggest that hormone therapy does not increase the risk of cardiovascular death in patients with clinically localized PCa and support the use of such therapy in settings with proven survival benefit. PMID- 26362092 TI - Kimura Disease Mimicking an Aneurysm of the Radial Artery. PMID- 26362093 TI - Reply: To PMID 25771389. PMID- 26362094 TI - Liver transplantation in severe methylmalonic acidemia: The sooner, the better. PMID- 26362095 TI - Infants' Dietary Diversity Scores: United States Breastfed Infants Fall Short. PMID- 26362097 TI - Comparative acceptance of pertussis and influenza immunization among health-care personnel. AB - BACKGROUND: Pertussis and influenza immunization in health-care professionals (HCP) has been shown to lead to significant reduction of nosocomial infections. Parallel campaigns of pertussis and seasonal influenza immunization gave us a unique opportunity to compare attitudes towards influenza and pertussis immunization among HCP and to determine acceptance rates for both or either one of the two immunizations or refusal of both. METHODS: A questionnaire was sent to HCP to anonymously obtain demographic data, profession, numbers of previous influenza immunizations, acceptance of influenza immunization in the current 2012/13 season, pertussis immunization currently or within the last 10 years, and reasons for acceptance or decline of pertussis and influenza vaccination. RESULTS: Of 638 HCP with patient contact, 314 (49%) responded and 303 (47%) were included in the analysis. Immunization acceptance rates were 33% for influenza, 57% for pertussis; 24% accepted both immunizations and 34% none of both. Acceptance of influenza immunization was significantly higher in those with one or more previous influenza vaccinations (p<0.005). Among 130 HCP who declined pertussis immunization, missed opportunity (28%) was the dominant reason. Of 204 HCP who declined influenza immunization, the most frequently stated reason was "lack of influenza immunization is not considered an issue" (36%). CONCLUSIONS: Misconceptions about the efficacy and necessity of pertussis and especially influenza immunization continue to prevail among HCP. Active promotion, personal encouragement, providing more immunization opportunities and other incentives are measures that should be considered to increase the rate of immunization among HCP. PMID- 26362098 TI - Synthetic virus seeds for improved vaccine safety: Genetic reconstruction of poliovirus seeds for a PER.C6 cell based inactivated poliovirus vaccine. AB - Safety of vaccines can be compromised by contamination with adventitious agents. One potential source of adventitious agents is a vaccine seed, typically derived from historic clinical isolates with poorly defined origins. Here we generated synthetic poliovirus seeds derived from chemically synthesized DNA plasmids encoding the sequence of wild-type poliovirus strains used in marketed inactivated poliovirus vaccines. The synthetic strains were phenotypically identical to wild-type polioviruses as shown by equivalent infectious titers in culture supernatant and antigenic content, even when infection cultures are scaled up to 10-25L bioreactors. Moreover, the synthetic seeds were genetically stable upon extended passaging on the PER.C6 cell culture platform. Use of synthetic seeds produced on the serum-free PER.C6 cell platform ensures a perfectly documented seed history and maximum control over starting materials. It provides an opportunity to maximize vaccine safety which increases the prospect of a vaccine end product that is free from adventitious agents. PMID- 26362096 TI - Alcohol alters hypothalamic glial-neuronal communications involved in the neuroendocrine control of puberty: In vivo and in vitro assessments. AB - The onset of puberty is the result of the increased secretion of hypothalamic luteinizing hormone-releasing hormone (LHRH). The pubertal process can be altered by substances that can affect the prepubertal secretion of this peptide. Alcohol is one such substance known to diminish LHRH secretion and delay the initiation of puberty. The increased secretion of LHRH that normally occurs at the time of puberty is due to a decrease of inhibitory tone that prevails prior to the onset of puberty, as well as an enhanced development of excitatory inputs to the LHRH secretory system. Additionally, it has become increasingly clear that glial neuronal communications are important for pubertal development because they play an integral role in facilitating the pubertal rise in LHRH secretion. Thus, in recent years attempts have been made to identify specific glial-derived components that contribute to the development of coordinated communication networks between glia and LHRH cell bodies, as well as their nerve terminals. Transforming growth factor-alpha and transforming growth factor-beta1 are two such glial substances that have received attention in this regard. This review summarizes the use of multiple neuroendocrine research techniques employed to assess these glial-neuronal communication pathways involved in regulating prepubertal LHRH secretion and the effects that alcohol can have on their respective functions. PMID- 26362100 TI - Modeling ant foraging: A chemotaxis approach with pheromones and trail formation. AB - We consider a continuous mathematical description of a population of ants and simulate numerically their foraging behavior using a system of partial differential equations of chemotaxis type. We show that this system accurately reproduces observed foraging behavior, especially spontaneous trail formation and efficient removal of food sources. We show through numerical experiments that trail formation is correlated with efficient food removal. Our results illustrate the emergence of trail formation from simple modeling principles. PMID- 26362099 TI - Immunogenicity and safety of a 13-valent pneumococcal conjugate vaccine in adults 18-49 years of age, naive to 23-valent pneumococcal polysaccharide vaccine. AB - BACKGROUND: Based on the success of vaccination with pneumococcal conjugate vaccines (PCVs) in children, recent studies have focused on PCVs in adults. Data from a randomized, double-blind study comparing the immunogenicity, tolerability, and safety of the 13-valent PCV (PCV13) and the 23-valent pneumococcal polysaccharide vaccine (PPSV23) in PPSV23-naive adults 60-64 years of age have been published. The same study also included a cohort of adults aged 18-49 years that received open-label PCV13. The purpose of this cohort was to examine the immunogenicity, safety, and tolerability of PCV13 in adult subjects 18-49 years of age compared with adults 60-64 years of age for whom PCV13 is approved. METHODS: Adults naive to PPSV23 were grouped by age into 2 cohorts: 18-49 years (n=899; further stratified by age into 3 subgroups 18-29, 30-39, and 40-49 years) and 60-64 years (n=417). All subjects received 1 dose of PCV13. In both age groups, immunogenicity was assessed by antipneumococcal opsonophagocytic activity (OPA) geometric mean titers (GMTs) and IgG geometric mean concentrations (GMCs) 1 month after vaccination. Safety and tolerability were evaluated. RESULTS: In adults aged 18-49 years, OPA GMTs and IgG GMCs were noninferior for all 13 serotypes and statistically significantly higher for all except 1 serotype (OPA GMT) and 5 serotypes (IgG GMCs) compared with adults 60-64 years. Immune responses were highest in the youngest age subgroup (18-29 years). Local reactions and systemic events were more common in adults 18-49 years compared with 60-64 years and were self-limited. CONCLUSION: Immune responses to PCV13 are robust in adults >=18 years of age, with highest responses observed in the youngest subgroup. Based on its safety and immunologic profile, PCV13 may serve an important therapeutic role in younger adults, particularly those with underlying medical conditions who have an increased risk of serious pneumococcal infections. PMID- 26362101 TI - The effect of intrinsic muscular nonlinearities on the energetics of locomotion in a computational model of an anguilliform swimmer. AB - Animals move through their environments using muscles to produce force. When an animal's nervous system activates a muscle, the muscle produces different amounts of force depending on its length, its shortening velocity, and its time history of force production. These muscle forces interact with forces from passive tissue properties and forces from the external environment. Using an integrative computational model that couples an elastic, actuated model of an anguilliform, lamprey-like swimmer with a surrounding Navier-Stokes fluid, we study the effects of this coupling between the muscle force and the body motion. Swimmers with different forms of this coupling can achieve similar motions, but use different amounts of energy. The velocity dependence is the most important property of the ones we considered for reducing energy costs and helping us to stabilize oscillations. These effects are strongly influenced by how rapidly the muscle deactivates; if force decays too slowly, muscles on opposite sides of the body end up fighting each other, increasing energy cost. Work-dependent deactivation, an effect that causes a muscle to deactivate more rapidly if it has recently produced mechanical work, works together with the velocity dependence to reduce the energy cost of swimming. PMID- 26362102 TI - Effects of adaptive protective behavior on the dynamics of sexually transmitted infections. AB - Sexually transmitted infections (STIs) continue to present a complex and costly challenge to public health programs. The preferences and social dynamics of a population can have a large impact on the course of an outbreak as well as the effectiveness of interventions intended to influence individual behavior. In addition, individuals may alter their sexual behavior in response to the presence of STIs, creating a feedback loop between transmission and behavior. We investigate the consequences of modeling the interaction between STI transmission and prophylactic use with a model that links a Susceptible-Infectious-Susceptible (SIS) system to evolutionary game dynamics that determine the effective contact rate. The combined model framework allows us to address protective behavior by both infected and susceptible individuals. Feedback between behavioral adaptation and prevalence creates a wide range of dynamic behaviors in the combined model, including damped and sustained oscillations as well as bistability, depending on the behavioral parameters and disease growth rate. We found that disease extinction is possible for multiple regions where R0>1, due to behavior adaptation driving the epidemic downward, although conversely endemic prevalence for arbitrarily low R0 is also possible if contact rates are sufficiently high. We also tested how model misspecification might affect disease forecasting and estimation of the model parameters and R0. We found that alternative models that neglect the behavioral feedback or only consider behavior adaptation by susceptible individuals can potentially yield misleading parameter estimates or omit significant features of the disease trajectory. PMID- 26362103 TI - Toward a biophysical understanding of the salt stress response of individual plant cells. AB - We present and explore a kinetic model of ion transport across and between the membranes of an isolated plant cell with an emphasis on the cell's response to salt (Na(+)) stress. The vacuole, cytoplasm and apoplast are treated as concentric regions separated by tonoplast and plasma membranes. The model includes the transport of Na(+), K(+), Cl(-) and H(+) across both membranes via primary active proton pumps, secondary active antiporters and symporters, as well as passive ion channels. In addition, water transport is included, allowing us to investigate both the osmotic and ionic components of salt stress. The model's predictions of steady state and transient cytosolic pH and Na(+) concentrations were found to be quantitatively comparable to measured experimental values. Through an extensive simulation study we have identified and characterized scenarios in which individual transport processes (H(+) pumps, Na(+)/H(+) antiporters and channels involved in the transport of Na(+)) and their combinations have major effects on the level of Na(+) in each of the cell compartments. This systematic study emulates the effects of overexpressing and inhibiting transporter genes by genetic modification and hence we have compared our simulations with observations from experiments conducted on transgenic plants. The simulations suggest that overexpressing tonoplast Na(+)/H(+) antiporter genes and tonoplast H(+) pump genes lead to an increase in the storage of Na(+) in the vacuole (helping the cell to maintain water uptake under salt stress), with only a transient influence on the cytoplasmic Na(+) concentration. The model predicts effects of varying the expression of transporter genes (individually or in combination) which have yet to be investigated in experiments. For example, our findings indicate that simultaneously overexpressing plasma membrane and tonoplast Na(+)/H(+) antiporter genes would lead to improvements in both ionic and osmotic stress tolerance. The results demonstrate the importance of simultaneously modelling the transport of Na(+) across both the tonoplast and plasma membrane, a task not undertaken previously. PMID- 26362104 TI - Identification of microRNA precursor with the degenerate K-tuple or Kmer strategy. AB - The microRNA (miRNA), a small non-coding RNA molecule, plays an important role in transcriptional and post-transcriptional regulation of gene expression. Its abnormal expression, however, has been observed in many cancers and other disease states, implying that the miRNA molecules are also deeply involved in these diseases, particularly in carcinogenesis. Therefore, it is important for both basic research and miRNA-based therapy to discriminate the real pre-miRNAs from the false ones (such as hairpin sequences with similar stem-loops). Most existing methods in this regard were based on the strategy in which RNA samples were formulated by a vector formed by their Kmer components. But the length of Kmers must be very short; otherwise, the vector's dimension would be extremely large, leading to the "high-dimension disaster" or overfitting problem. Inspired by the concept of "degenerate energy levels" in quantum mechanics, we introduced the "degenerate Kmer" (deKmer) to represent RNA samples. By doing so, not only we can accommodate long-range coupling effects but also we can avoid the high-dimension problem. Rigorous jackknife tests and cross-species experiments indicated that our approach is very promising. It has not escaped our notice that the deKmer approach can also be applied to many other areas of computational biology. A user friendly web-server for the new predictor has been established at http://bioinformatics.hitsz.edu.cn/miRNA-deKmer/, by which users can easily get their desired results. PMID- 26362105 TI - Homology modeling, functional annotation and comparative genomics of outer membrane protein H of Pasteurella multocida. AB - Pasteurella multocida is an important pathogen of animals and humans. Outer Membrane Protein (Omp) H is a major conserved protein in the envelope of P. multocida and has been commonly targeted as a protective antigen. However, not much is known about its structure and function due to the difficulties that are typically associated with obtaining sufficient amounts of purified prokaryotic transmembrane proteins. The present work is aimed at studying the OmpH using an in silico approach and consolidate the findings in light of existing experimental evidences. Our study describes the first 3D model of the P. multocida OmpH obtained through a combination of several in silico modeling approaches. From our results, OmpH of P. multocida could be classified as a homotrimeric, 16 stranded, beta-barrel porin involved in the non-specific transport of small, hydrophilic molecules, serving essential osmoregulatory function. Moreover, very small homologous sequences could be identified in the host proteome, strengthening the probability of a successful OmpH-based vaccine against the pathogen with remote chances of cross-reaction to host proteins. PMID- 26362107 TI - Effects of EGCG content in green tea extract on pharmacokinetics, oxidative status and expression of inflammatory and apoptotic genes in the rat ocular tissues. AB - Green tea extract (GTE) exerts antioxidative activities in ocular tissues of rats, but high levels of (-)-epigallocatechin gallate (EGCG) can induce oxidative stress. In this study, pharmacokinetics, diurnal variation of oxidative status, antioxidation and transcription factors changes in ocular tissues of rats were investigated. Rats were fed intragastrically with GTE and catechin mixtures containing different amounts of EGCG. Plasma and various ocular tissues were taken for pharmacokinetic analysis, oxidation marker testings and gene expression assays. Effects of EGCG on ocular oxidation status were assessed by 8-isoprostane level and reduced/oxidized glutathione ratio. Oxidation, inflammation and apoptosis regulations in retina were evaluated by real-time polymerase chain reaction. Epicatechin, epigallocatechin and EGCG were dominant in various ocular tissues except vitreous humor, where gallocatechin was predominant. Diurnal variation of oxidative status was found in some compartments. GTE caused oxidative stress increase in the plasma, aqueous humor, vitreous humor, cornea and retina but decrease in the lens and choroid-sclera. Catechins mixture containing half dose of EGCG lowered 8-isoprostane in the retina and lens. GTE treatment induced superoxide dismutase 1 and glutathione peroxidase-3 expressions but suppressed catalase in the retina. Our results reveal pro-oxidation of GTE with high EGCG content to the ocular tissues. Optimal EGCG level is needed for protection. PMID- 26362106 TI - Inhaled Cannabis for Chronic Neuropathic Pain: A Meta-analysis of Individual Patient Data. AB - Chronic neuropathic pain, the most frequent condition affecting the peripheral nervous system, remains underdiagnosed and difficult to treat. Inhaled cannabis may alleviate chronic neuropathic pain. Our objective was to synthesize the evidence on the use of inhaled cannabis for chronic neuropathic pain. We performed a systematic review and a meta-analysis of individual patient data. We registered our protocol with PROSPERO CRD42011001182. We searched in Cochrane Central, PubMed, EMBASE, and AMED. We considered all randomized controlled trials investigating chronic painful neuropathy and comparing inhaled cannabis with placebo. We pooled treatment effects following a hierarchical random-effects Bayesian responder model for the population-averaged subject-specific effect. Our evidence synthesis of individual patient data from 178 participants with 405 observed responses in 5 randomized controlled trials following patients for days to weeks provides evidence that inhaled cannabis results in short-term reductions in chronic neuropathic pain for 1 in every 5 to 6 patients treated (number needed to treat = 5.6 with a Bayesian 95% credible interval ranging between 3.4 and 14). Our inferences were insensitive to model assumptions, priors, and parameter choices. We caution that the small number of studies and participants, the short follow-up, shortcomings in allocation concealment, and considerable attrition limit the conclusions that can be drawn from the review. The Bayes factor is 332, corresponding to a posterior probability of effect of 99.7%. PERSPECTIVE: This novel Bayesian meta-analysis of individual patient data from 5 randomized trials suggests that inhaled cannabis may provide short-term relief for 1 in 5 to 6 patients with neuropathic pain. Pragmatic trials are needed to evaluate the long term benefits and risks of this treatment. PMID- 26362108 TI - Case with Brunsting-Perry-like localized subepidermal blister formations and immunoglobulin G antibodies against unidentified basement membrane zone antigen. AB - Brunsting-Perry type bullous pemphigoid is defined by the blister formation limited to the head and neck, and autoantibodies to type VII collagen are detected in several cases. However, the pathomechanisms and autoantigens in this condition remain unknown. We report a 20-year-old female patient with a more than 2-year history of recurrent tense blisters localized on the face with no distinct atrophic scar formation. The patient had neither extensive sun exposure nor a history suggestive of contact dermatitis. Oral betamethasone was effective on the skin lesions. Histopathology revealed subepidermal blister formation with dermal infiltrates of neutrophils. Although direct and indirect immunofluorescence tests detected immunoglobulin G antibodies to the basement membrane zone (BMZ), no known dermal or epidermal autoantigens were detected in immunoblot analyses. Therefore, this case may be a rare variant of Brunsting-Perry type localized bullous pemphigoid with autoantibodies to an undetermined BMZ antigen. PMID- 26362110 TI - The effect of oral collagen peptide supplementation on skin moisture and the dermal collagen network: evidence from an ex vivo model and randomized, placebo controlled clinical trials. AB - BACKGROUND: Skin dryness and an accelerated fragmentation of the collagen network in the dermis are hallmarks of skin aging. Nutrition is a key factor influencing skin health and consequently its appearance. A wide range of dietary supplements is offered to improve skin health. Collagen peptides are used as a bioactive ingredient in nutricosmetic products and have been shown in preclinical studies to improve skin barrier function, to induce the synthesis of collagen and hyaluronic acid, and to promote fibroblast growth and migration. Our aim was to investigate the effect of oral supplementation with specific collagen peptides on skin hydration and the dermal collagen network in a clinical setting. METHODS: Two placebo-controlled clinical trials were run to assess the effect of a daily oral supplementation with collagen peptides on skin hydration by corneometry, on collagen density by high-resolution ultrasound and on collagen fragmentation by reflectance confocal microscopy. Human skin explants were used to study extracellular matrix components in the presence of collagen peptides ex vivo. RESULTS: Oral collagen peptide supplementation significantly increased skin hydration after 8 weeks of intake. The collagen density in the dermis significantly increased and the fragmentation of the dermal collagen network significantly decreased already after 4 weeks of supplementation. Both effects persisted after 12 weeks. Ex vivo experiments demonstrated that collagen peptides induce collagen as well as glycosaminoglycan production, offering a mechanistic explanation for the observed clinical effects. CONCLUSION: The oral supplementation with collagen peptides is efficacious to improve hallmarks of skin aging. PMID- 26362109 TI - Structural and mechanistic insights on nitrate reductases. AB - Nitrate reductases (NR) belong to the DMSO reductase family of Mo-containing enzymes and perform key roles in the metabolism of the nitrogen cycle, reducing nitrate to nitrite. Due to variable cell location, structure and function, they have been divided into periplasmic (Nap), cytoplasmic, and membrane-bound (Nar) nitrate reductases. The first crystal structure obtained for a NR was that of the monomeric NapA from Desulfovibrio desulfuricans in 1999. Since then several new crystal structures were solved providing novel insights that led to the revision of the commonly accepted reaction mechanism for periplasmic nitrate reductases. The two crystal structures available for the NarGHI protein are from the same organism (Escherichia coli) and the combination with electrochemical and spectroscopic studies also lead to the proposal of a reaction mechanism for this group of enzymes. Here we present an overview on the current advances in structural and functional aspects of bacterial nitrate reductases, focusing on the mechanistic implications drawn from the crystallographic data. PMID- 26362111 TI - Captures of Ostrinia furnacalis (Lepidoptera: Crambidae) With Sex Pheromone Traps in NE China Corn and Soybeans. AB - Ostrinia furnacalis (Guenee) (Lepidoptera: Crambidae), commonly referred to as the Asian corn borer, is the most important corn pest in Asia. Although capturing males with pheromone traps has recently been the main monitoring tool and suppression technique, the best trap designs remain unclear. Commercially available Delta and funnel traps, along with laboratory-made basin and water traps, and modified Delta traps, were evaluated in corn and soybean fields during 2013-2014 in NE China. The water trap was superior for capturing first-generation O. furnacalis (1.37 times the Delta trap). However, the basin (8.3 +/- 3.2 moths/trap/3 d), Delta (7.9 +/- 2.5), and funnel traps (7.0 +/- 2.3) were more effective than water traps (1.4 +/- 0.4) during the second generation. Delta traps gave optimal captures when deployed at ca. 1.57 * the highest corn plants, 1.36* that of average soybean plants, and at the field borders. In Delta traps modified by covering 1/3 of their ends, captures increased by ca. 15.7 and 8.1% in the first and second generations, respectively. After 35 d in the field, pheromone lures were still ca. 50% as attractive as fresh lures, and retained this level of attraction for ca. 25 more days. Increased captures (first and second generation: 90.9 +/- 9.5%; 78.3 +/- 9.3%) were obtained by adding a lure exposed for 5 d to funnel traps baited with a 35-d lure. PMID- 26362112 TI - Quantitative genetic variance in experimental fly populations evolving with or without environmental heterogeneity. AB - Heterogeneous environments are typically expected to maintain more genetic variation in fitness within populations than homogeneous environments. However, the accuracy of this claim depends on the form of heterogeneity as well as the genetic basis of fitness traits and how similar the assay environment is to the environment of past selection. Here, we measure quantitative genetic (QG) variance for three traits important for fitness using replicated experimental populations of Drosophila melanogaster evolving under four selective regimes: constant salt-enriched medium (Salt), constant cadmium-enriched medium (Cad), and two heterogeneous regimes that vary either temporally (Temp) or spatially (Spatial). As theory predicts, we found that Spatial populations tend to harbor more genetic variation than Temp populations or those maintained in a constant environment that is the same as the assay environment. Contrary to expectation, Salt populations tend to have more genetic variation than Cad populations in both assay environments. We discuss the patterns for QG variances across regimes in relation to previously reported data on genome-wide sequence diversity. For some traits, the QG patterns are similar to the diversity patterns of ecological selected SNPs, whereas the QG patterns for some other traits resembled that of neutral SNPs. PMID- 26362113 TI - Synthesis, In vitro and Docking Studies of New Flavone Ethers as alpha Glucosidase Inhibitors. AB - We report herein the synthesis, alpha-glucosidase inhibition and docking studies for a series of 3-15 new flavones. A simple nucleophilic substitution reaction takes place between 3'hydroxyflavone (2) with halides to afford the new flavones. Chalcone (1), 3'hydroxyflavone (2) and the newly synthesized flavones (3-15) were being evaluated for their ability to inhibit activity of alpha-glucosidase. Compounds 2, 3, 5, 7-10 and 13 showed good inhibitory activity with IC50 values ranging between 1.26 and 36.44 MUM as compared to acarbose (IC50 = 38.25 +/- 0.12 MUM). Compounds 5 (5.45 +/- 0.08 MUM), 7 (1.26 +/- 0.01 MUM) and 8 (8.66 +/- 0.08 MUM) showed excellent inhibitory activity, and this may be due to trifluoromethyl substitution that is common for these compounds. Compound 7, a 2,5 trifluoromethyl-substituted compound, recorded the highest inhibition activity, and it is thirty times better than the standard drug. Docking studies for compound 7 suggest that both trifluoromethyl substituents are well positioned in a binding pocket surrounded by Phe300, Phe177, Phe157, Ala278, Asp68, Tyr71 and Asp214. The ability of compound 7 to interact with Tyr71 and Phe177 is extremely significant as they are found to be important for substrates recognition by alpha glucosidase. PMID- 26362114 TI - How to do one-handed tying of double half knot: alternative implementation. PMID- 26362115 TI - Impact of Ternary Solvent System in Stability-Indicating Assay Method of Bambuterol: Design of Experiments Approach. AB - High-performance liquid chromatography method for anti-asthmatic beta2-agonist drug bambuterol, its process-related impurities and its major degradation products was developed and validated using quality by design concept. A 3(3) full factorial design was employed to study the effect of three independent factors, namely, ratio of organic modifiers in mobile phase, pH of the buffer and flow rate of the mobile phase. The responses considered were retention time of the last peak and resolution of poorly separated peaks (drug and PR-4 and drug and DP 3). The optimum conditions for separation were determined with the aid of design of experiments. The optimized ternary solvent composition was a mixture of 10 mM ammonium acetate buffer (pH 6.0), methanol and acetonitrile in the ratio of 90:5: 5 (v/v/v) in solvent reservoir A and 10:45:45 (v/v/v) in solvent reservoir B. The separation of the analytes was achieved by using a gradient method. The predictability criteria of the optimized method demonstrated good correlation between observed and predicted response. The method was validated for specificity, linearity, accuracy, precision and robustness in compliance with the International Conference on Harmonization guidelines Q2R1. PMID- 26362116 TI - Performing red reflex eye examinations increases the rate of neonatal conjunctivitis. AB - AIM: Red reflex eye examinations often require opening the eyelids, risking infection. We evaluated links between this procedure and neonatal conjunctivitis. METHODS: We divided 18 872 neonates of more than 35 weeks of gestation into two birth periods, 2008-2009 and 2010-2011, before and after red reflex examinations were carried out by our facility. The rates of clinical conjunctivitis, bacterial conjunctivitis and bacterial growth percentage were compared between the two periods. RESULTS: The 2010-2011 period included more Caesarean deliveries and longer lengths of stay (LOS) than the 2008-2009 period. The clinical conjunctivitis rate increased significantly during 2010-2011 (p = 0.029), but the bacterial conjunctivitis and bacterial growth percentages did not differ between the two periods. Variables that were independently and significantly associated with clinical conjunctivitis included being born in 2010-2011, with an odds ratio (OR) of 1.22, male gender (OR 1.31) and LOS (OR 1.19). Bacterial conjunctivitis was associated with vaginal delivery (OR 3.65), males delivered by Caesarean (OR 2.68) and LOS (OR 1.37). CONCLUSION: Clinical conjunctivitis was significantly associated with the later study period, male gender and LOS. Conjunctival swab sampling increased significantly following the implementation of red reflex examinations, but without changes in the bacterial conjunctivitis rate and the bacterial growth percentage. PMID- 26362117 TI - Circadian clock speed increases during aging in the male Syrian hamster: A large scale study. AB - There are conflicting reports in the literature as to whether or not the circadian period in Syrian hamsters shortens with age, and those studies were conducted with small sample sizes. This report mines data from a large number of experiments resulting in more than 1000 measurements of circadian period in hamsters during aging up to 6 months, and this was correlated with both age and weight. Circadian period was calculated while hamsters were in running wheels in constant darkness. There is a weak correlation between hamster weight and circadian period, and there is significant shortening of circadian period during aging. PMID- 26362118 TI - Different Response of Carbonyl Carotenoids to Solvent Proticity Helps To Estimate Structure of the Unknown Carotenoid from Chromera velia. AB - In order to estimate the possible structure of the unknown carbonyl carotenoid related to isofucoxanthin from Chromera velia denoted as isofucoxanthin-like carotenoid (Ifx-l), we employed steady-state and ultrafast time-resolved spectroscopic techniques to investigate spectroscopic properties of Ifx-l in various solvents. The results were compared with those measured for related carotenoids with known structure: fucoxanthin (Fx) and isofucoxanthin (Ifx). The experimental data were complemented by quantum chemistry calculations and molecular modeling. The data show that Ifx-l must have longer effective conjugation length than Ifx. Yet, the magnitude of polarity-dependent changes in Ifx-l is larger than for Ifx, suggesting significant differences in structure of these two carotenoids. The most interesting spectroscopic feature of Ifx-l is its response to solvent proticity. The transient absorption data show that (1) the magnitude of the ICT-like band of Ifx-l in acetonitrile is larger than in methanol and (2) the S1/ICT lifetime of Ifx-l in acetonitrile, 4 ps, is markedly shorter than in methanol (10 ps). This is opposite behavior than for Fx and Ifx whose S1/ICT lifetimes are always shorter in protic solvent methanol (20 and 13 ps) than in aprotic acetonitrile (30 and 17 ps). Comparison with other carbonyl carotenoids reported earlier showed that proticity response of Ifx-l is consistent with presence of a conjugated lactone ring. Combining the experimental data and quantum chemistry calculations, we estimated a possible structure of Ifx l. PMID- 26362119 TI - Synergistic effect of Pseudomonas putida and Bacillus amyloliquefaciens ameliorates drought stress in chickpea (Cicer arietinum L.). AB - Two plant growth promoting rhizobacteria (PGPR) Pseudomonas putida NBRIRA and Bacillus amyloliquefaciens NBRISN13 with ability to tolerate abiotic stress along with multiple PGP traits like ACC deaminase activity, minerals solubilisation, hormones production, biofilm formation, siderophore activity were evaluated for their synergistic effect to ameliorate drought stress in chickpea. Earlier we have reported both the strains individually for their PGP attributes and stress amelioration in host plants. The present study explains in detail the possibilities and benefits of utilizing these 2 PGPR in consortium for improving the chickpea growth under control and drought stressed condition. In vitro results clearly demonstrate that both the PGPR strains are compatible to each other and their synergistic growth enhances the PGP attributes. Greenhouse experiments were conducted to evaluate the effect of inoculation of both strains individually and consortia in drought tolerant and sensitive cultivars (BG362 and P1003). The growth parameters were observed significantly higher in consortium as compared to individual PGPR. Colonization of both PGPR in chickpea rhizosphere has been visualized by using gfp labeling. Apart from growth parameters, defense enzymes, soil enzymes and microbial diversity were significantly modulated in individually PGPR and in consortia inoculated plants. Negative effects of drought stress has been ameliorated and apparently seen by higher biomass and reversal of stress indicators in chickpea cultivars treated with PGPR individually or in consortia. Findings from the present study demonstrate that synergistic application has better potential to improve plant growth promotion under drought stress conditions. PMID- 26362120 TI - Safety Assessment of Alkyl Esters as Used in Cosmetics. AB - The Cosmetic Ingredient Review Expert Panel (Panel) assessed the safety of 237 alkyl esters for use in cosmetics. The alkyl esters included in this assessment have a variety of reported functions in cosmetics, with skin-conditioning agent being the most common function. The Panel reviewed available animal and clinical data in making its determination of safety on these ingredients, and where there were data gaps, similarity in structure, properties, functions, and uses of these ingredients allowed for extrapolation of the available toxicological data to assess the safety of the entire group. The Panel concluded that these ingredients are safe in cosmetic formulations in the present practices of use and concentration when formulated to be nonirritating. PMID- 26362121 TI - Safety Assessment of Alkyl PEG Sulfosuccinates as Used in Cosmetics. AB - The Cosmetic Ingredient Review (CIR) Expert Panel (Panel) reviewed the safety of alkyl polyethylene glycol (PEG) sulfosuccinates, which function in cosmetics mostly as surfactants/cleansing agents. Although these ingredients may cause ocular and skin irritation, dermal penetration is unlikely because of the substantial polarity and molecular size of these ingredients. The Panel considered the negative oral carcinogenicity and reproductive and developmental toxicity data on chemically related laureths (PEG lauryl ethers) and negative repeated dose toxicity and skin sensitization data on disodium laureth sulfosuccinate supported the safety of these alkyl PEG sulfosuccinates in cosmetic products, but. The CIR Expert Panel concluded that the alkyl PEG sulfosuccinates are safe in the present practices of use and concentration when formulated to be nonirritating. PMID- 26362122 TI - Safety Assessment of Ethanolamine and Ethanolamine Salts as Used in Cosmetics. AB - The Cosmetic Ingredient Review (CIR) Expert Panel (Panel) assessed the safety of ethanolamine and 12 salts of ethanolamine as used in cosmetics. Ethanolamine functions as a pH adjuster. The majority of the salts are reported to function as surfactants, and the others are reported to function as pH adjusters, hair fixatives, or preservatives. The Panel reviewed available animal and clinical data, as well as information from previous relevant CIR reports. Because data were not available for each individual ingredient and because the salts dissociate freely in water, the Panel extrapolated from those previous reports to support safety. The Panel concluded that these ingredients are safe in the present practices of use and concentrations (rinse-off products only) when formulated to be nonirritating, and these ingredients should not be used in cosmetic products in which N-nitroso compounds may be formed. PMID- 26362123 TI - Safety Assessment of Pentaerythrityl Tetraesters as Used in Cosmetics. AB - The Cosmetic Ingredient Review (CIR) Expert Panel (Panel) reviewed the safety of 16 pentaerythrityl tetraester compounds as used in cosmetics. These ingredients mostly function as hair-conditioning agents, skin-conditioning agents miscellaneous and binders, skin-conditioning agents-occlusive, viscosity increasing agents-nonaqueous, and skin-conditioning agents-emollient. The Panel reviewed the available animal and human data related to these ingredients and previous safety assessments of the fatty acid moieties. The Panel concluded that pentaerythrityl tetraisostearate and the other pentaerythrityl tetraester compounds were safe in the practices of use and concentration as given in this safety assessment. PMID- 26362124 TI - Selection of non-steroidal anti-inflammatory drug and treatment regimen for sulfur mustard-induced cutaneous lesions. AB - The inflammatory process plays an important role in sulfur mustard (HD) injury and HD pathogenesis, suggesting that anti-inflammatory treatments applied as soon as possible following HD injury may reduce tissue damage and accelerate healing. This study used the HD dermal weanling swine model to investigate the efficacy of two non-steroidal anti-inflammatory drugs, capsaicin and diclofenac, when applied in combination with the steroid, clobetasol. The therapeutic regimen was also investigated with respect to initiation of treatment post-exposure, frequency and duration. Yorkshire-cross pigs were randomly assigned to experimental groups, corresponding to all combinations of treatment (capsaicin with clobetasol or diclofenac with clobetasol), onset time (1, 2 or 4 h post-exposure), treatment duration (1, 3 or 5 days) and frequency of applications (2, 3 or 4 per day). For each animal, two sites on the ventral abdomen were exposed to 400 MUL of neat HD for 8 min to achieve superficial dermal (SD) lesions and two sites were exposed to 400 MUL neat HD for 30 min to achieve deep dermal (DD) lesions. Each treatment regimen was tested against a SD and a DD injury. Untreated SD and DD lesion sites served as within-animal controls. Assessments, up to one week post-challenge, included digital photographs, clinical assessments (lesion size measurements and modified Draize scoring), transepidermal water loss (TEWL), reflectance colorimetry and histopathologic evaluations that included an estimate for depth of injury and wound healing parameters. Diclofenac plus clobetasol treatment resulted in significant reductions in lesion contracture and modified Draize scores, increased barrier function (decreased TEWL), and increased healing as determined by histopathology for both SD and DD injury when compared with untreated sites and sites treated with capsaicin plus clobetasol. An increased duration of treatment from 1 to 5 days was most commonly associated with decreased clinical assessment and histopathological severity scores. Therefore, a combination of diclofenac and clobetasol application, when administered for at least five days, shows promise in ameliorating HD-induced lesions. PMID- 26362125 TI - Nutraceuticals for blood pressure control. AB - Significant effects on blood pressure (BP) have been reported from large nutritional interventions, particularly the Dietary Approaches to Stop Hypertension (DASH) and the Mediterranean diet. In more recent years, numerous studies have investigated the possible BP-lowering effect of different nutraceuticals; these range from specific foods to minerals, lipids, whole proteins, peptides, amino acids, probiotics, and vitamins. While a very large body of evidence supports the use of potassium, L-arginine, vitamins C and D, cocoa flavonoids, beetroot juice, some probiotics, coenzyme Q10, controlled release melatonin, aged garlic extract, and coffee, the use of other nutraceuticals, such as green tea, flaxseed, and resveratrol, has not as yet been supported by adequate evidence. In some cases, e.g. proteins/peptides, the responsible component needs also to be fully uncovered. Finally, while for most of the products only short-term studies are available, with no specific end points, an ongoing very large prospective study on chocolate flavanols will answer the question whether this may reduce cardiovascular risk. Thus, in addition to data on long-term safety, further clinical research is advisable in order to identify, among active nutraceuticals, those with the best cost effectiveness and risk-benefit ratio for a wide use in the general population with a raised cardiovascular risk consequent to uncomplicated hypertension. PMID- 26362126 TI - Abuse, Neglect, and Violence Against Elderly Women in Ghana: Implications for Social Justice and Human Rights. AB - This article discusses abuse and neglect of elderly women in Ghana and the traditional practices that adversely affect their human rights. Their situation is characterized by pervasive poverty, illiteracy, widowhood, predominantly rural dwelling, and subjection to insidious cultural practices and superstitious beliefs. Increase in life expectancy and population trends point to significant increases in the numbers of the elderly women. Breakdown of the extended family support system and the waning of filial obligations are factors affecting their welfare. Accurate data on these abuses is lacking due to cultural inhibitions and non-reporting. Legislations and NGO programs are addressed to combat abuses. PMID- 26362127 TI - Effect of temperature on the release of carvacrol and cinnamaldehyde incorporated into polymeric systems to control growth and biofilms of Escherichia coli and Staphylococcus aureus. AB - This study assessed the effect of temperature on the release of essential oil components incorporated by melt compounding into polymeric films. Specifically, polyethylene-co-vinylacetate (EVA) films containing carvacrol (CAR) and cinnamaldehyde (ALD), alone and in combination, were prepared and their surface and mechanical properties and antibacterial and anti-biofilm activity against Escherichia coli and Staphylococcus aureus were evaluated. The addition of ALD and CAR did not provoke variation in the surface morphology of EVA and allowed their delivery. At 37 degrees C, films containing CAR, ALD or their combination (25+75%) were found to have the strongest bactericidal effect, whereas at lower temperatures a lower killing rate was observed. There was no clear evidence of the influence of temperature on the anti-biofilm activity of the essential oil component-based polymeric films. The biomass formed on EVA containing ALD, CAR or their combination (25+75) was significantly lower (60-80% reduction) than that formed on the EVA control at both 37 degrees and 22 degrees C. PMID- 26362128 TI - Proteolytic regulation of metabolic enzymes by E3 ubiquitin ligase complexes: lessons from yeast. AB - Eukaryotic organisms use diverse mechanisms to control metabolic rates in response to changes in the internal and/or external environment. Fine metabolic control is a highly responsive, energy-saving process that is mediated by allosteric inhibition/activation and/or reversible modification of preexisting metabolic enzymes. In contrast, coarse metabolic control is a relatively long term and expensive process that involves modulating the level of metabolic enzymes. Coarse metabolic control can be achieved through the degradation of metabolic enzymes by the ubiquitin-proteasome system (UPS), in which substrates are specifically ubiquitinated by an E3 ubiquitin ligase and targeted for proteasomal degradation. Here, we review select multi-protein E3 ligase complexes that directly regulate metabolic enzymes in Saccharomyces cerevisiae. The first part of the review focuses on the endoplasmic reticulum (ER) membrane-associated Hrd1 and Doa10 E3 ligase complexes. In addition to their primary roles in the ER associated degradation pathway that eliminates misfolded proteins, recent quantitative proteomic analyses identified native substrates of Hrd1 and Doa10 in the sterol synthesis pathway. The second part focuses on the SCF (Skp1-Cul1-F-box protein) complex, an abundant prototypical multi-protein E3 ligase complex. While the best-known roles of the SCF complex are in the regulation of the cell cycle and transcription, accumulating evidence indicates that the SCF complex also modulates carbon metabolism pathways. The increasing number of metabolic enzymes whose stability is directly regulated by the UPS underscores the importance of the proteolytic regulation of metabolic processes for the acclimation of cells to environmental changes. PMID- 26362129 TI - Can Platelet Count and Platelet Indices Predict the Risk and the Prognosis of Preeclampsia? AB - OBJECTIVE: To compare the hematocrit, platelet count (PC), mean platelet volume (MPV), platelet distribution width (PDW), PC to MPV ratio in the mild preeclamptic (mPE), severe preeclamptic (sPE) and healthy normotensive pregnant women to evaluate whether these parameters have a predictive and prognostic significance in determining the risk and the severity of preeclampsia (PE). METHODS: A retrospective case-control study was designed including the patient population (N = 284) composed of 49 mPE, 70 sPE, 165 healthy normotensive pregnant women for controls. Preceding medical histories of all the cases were insignificant. RESULTS: In comparison of the preeclamptic patients with controls; there was statistically significant difference in PC (p = 0.023; p < 0.05), MPV(p = 0.023; p < 0.05), PC/MPV ratio (p = 0.005; p < 0.01). But there was no difference between sPE and mPE. Cut-off value for MPV was calculated as 9 for the diagnosis of PE (p < 0.01), the odds ratio was 1.999. The cut off value for PC was 190, the odds ratio was 1.932. The cut off value was 19.9 for the PLT/MPV, the odds ratio was 2.42. CONCLUSION: We suggest that the increasing platelet turnover in PE causes a decrease in the PC, an increase of MPV value and especially a decrease in PC/MPV ratio pointing that these parameters may play an important role in predicting the risk of PE while they have no role on predicting the severity of PE. According to our findings we can suggest that the patients with these cut-off values of PC and platelet indices, should be carefully followed for the development of PE. PMID- 26362130 TI - [Mid-dermal elastolysis after insertion of a pacemaker]. AB - BACKGROUND: Mid-dermal elastolysis (MDE) is a rare acquired disease of elastic tissue histologically characterized by focal loss of elastic fibres within the mid-dermis. While the mechanisms leading to MDE remain unknown, increased degradation of elastic fibres may be involved. Many factors potentially triggering such degradation have been suggested. PATIENTS AND METHODS: A 58-year old man consulted for an asymptomatic reticulated eruption that began in the area of a pacemaker implanted six weeks earlier. The eruption consisted of erythematous polycyclic and coalescing macules with a wrinkled centre. Histopathology with orcein staining revealed focal loss of elastic fibres in the superficial reticular dermis only. Hypersensitivity reaction to any components of the pacemaker was ruled out by means of allergy exploration. Laboratory investigations including autoimmunological and haematological factors were unremarkable. A diagnosis was made of a reticular variant of MDE following insertion of a pacemaker. DISCUSSION: We report the second case of MDE following the insertion of a pacemaker, which could have triggered an inflammatory response directed specifically towards the elastic fibres. PMID- 26362131 TI - [Oral hairy leukoplakia induced by topical steroids]. AB - BACKGROUND: Oral hairy leukoplakia (OHL) is an EBV-associated condition of the oral mucosa, which is often painless. It is found predominantly in HIV-positive patients and is considered a clinical indicator of immunosuppression. OHL has rarely been described in HIV-negative patients, being found most often in association with iatrogenic immunosuppression. OHL induced by topical steroids remains extremely rare. PATIENTS AND METHODS: An 81-year-old HIV-negative woman, treated for 3 months with topical steroids for oral lichen planus, developed an asymptomatic white, corrugated, non-removable plaque with vertical folds on the lateral edge of the tongue. Associated oral candidiasis was noted. Based upon histological findings and in situ hybridisation showing numerous EBV-infected epithelial cells, a diagnosis of oral hairy leucoplakia was made. DISCUSSION AND CONCLUSION: To our knowledge, we report herein only the second recorded case of OHL induced strictly by topical steroids. Self-medication and poor adherence to dosage recommendations were noted in the patient's medical history. Physicians must be aware of the rare but nevertheless possible adverse events associated with topical steroid use, particularly when such medication is prescribed over a long period for inflammatory diseases of the oral mucosa. PMID- 26362132 TI - [Outpatient expectations in dermatology consultations: A pilot study]. AB - BACKGROUND: Understanding patients' expectations with regard to medical care is critical as it guarantees an efficient therapeutic process. Our aim was to determine outpatients' expectations concerning clinical encounters in a dermatology clinic and to study how these matched the opinions of dermatologists regarding them. PATIENTS AND METHODS: Consecutive outpatients consulting in five dermatology centres in the Paris suburbs between February 2013 and March 2013 were prospectively included. For this pilot cross-sectional study, we used two standardized forms to collect data from patients and dermatologists. Patients' answers were compared to those of their dermatologist, and the degree of matching was calculated to assess the ability of dermatologists to accurately identify their patients' expectations. RESULTS: Two hundred and sixty-five patients were included, with a median age of 41 years (interquartile range: 25; 62), of whom 166 were women (65.4%). Patient's principal expectations concerned diagnosis (51.7%) and medication (40.8%), with 32.1% of patients requiring reassurance. The rates of matching between patients' and dermatologists' answers ranged from 33.3% to 65.7% according to the type of expectations. The highest rate concerned expectation with regard to medications, being only 52.6% and 58.8%, respectively for expectations regarding diagnosis and the need for reassurance. CONCLUSION: This study highlights the need for improved identification of outpatient expectations in dermatology consultations. PMID- 26362133 TI - [Syphilis in Montpellier, France, from 2002 to 2011: Survey in a free hospital screening centre for venereal disease and in the dermatology unit of a regional public hospital]. AB - BACKGROUND: In a context of resurgent syphilis in France since 2000, we conducted a retrospective study in two different centres in Montpellier, France: the dermatology department of a public hospital and an anonymous and free centre for provision of information, diagnosis and treatment of venereal diseases (CDAG CIDDIST). PATIENTS AND METHODS: All patients with syphilis seen from January 2002 to December 2011 were included with the collaboration of the National Health Institute (InVS) and the Bacteriology Department of the public hospital. Epidemiology, clinical presentation, serological data, and treatment and monitoring data for up to 2 years were recorded. RESULTS: One hundred and seventy five cases of syphilis were diagnosed: 154 at the CDAG and 21 at the dermatology unit. Ninety-six percent of cases concerned men with a median age of 36 years. Eighty-two percent of these cases involved men having sex with men (MSM). Forty nine percent of cases were diagnosed in the secondary stage, 22% in the primary stage and 28% in the latent stage. The treatment administered in the majority of cases (73%) was benzathine-penicillin G. The numbers of patients showing incomplete follow-up were equal at both centres, with 31 patients (17.7%) failing to attend the follow-up visit. A decrease of at least 2 dilutions in VDRL score occurred in the year following treatment for 93 of 103 patients (90%). Patients managed at the dermatology department were older than their counterparts managed at the CDAG and exhibited more frequent cutaneous eruptions (58% vs. 3%, P<0.0001) but were less frequently bisexual. However, no significant differences were seen concerning sex and associated infections (hepatitis, gonococcal infection, HPV or herpes). DISCUSSION: Syphilis is on the rise, especially in the MSM population. The epidemiological characteristics of our cohort were consistent with those of other Western European countries. Although the reasons for consultation differed between CDAG/CIDDIST and the dermatology department, the two centres are complementary. Benzathine-penicillin G was the most commonly used treatment, in accordance with the recommendations. Measures must be introduced to improve patient monitoring without compromising anonymity. PMID- 26362134 TI - [Albinism and folliculitis keloidalis nuchae in a man of African descent]. PMID- 26362135 TI - Comparison of Outcomes of Hepatic Resection and Radiofrequency Ablation for Hepatocellular Carcinoma Patients with Multifocal Tumors Meeting the Barcelona Clinic Liver Cancer Stage A Classification. AB - BACKGROUND: Although hepatic resection (HR) has been recommended as the first line treatment option for patients with a solitary tumor, the first-line treatment for patients with multifocal tumors meeting the Barcelona-Clinic Liver Cancer (BCLC) stage A still remains unclear. This study compared outcomes for patients with multifocal tumors meeting the BCLC stage A treated by HR and radiofrequency ablation (RFA). STUDY DESIGN: A total of 384 consecutive patients with multifocal tumors meeting the BCLC stage A, who underwent HR (n = 224) or RFA (n = 160), were included. Moreover, propensity score-matched patients were analyzed to adjust for baseline differences. RESULTS: The 1-, 3-, and 5-year overall survival (OS) rates after HR and RFA were 96%, 71.7%, and 36.3%, and 90.0%, 72.7%, and 37.8%, respectively (p = 0.609); HR provided significantly better recurrence-free survival (RFS) rates than RFA at 1, 3, and 5 years (87.5%, 53.1%, and 20.1% vs 83.1%, 34.0%, and 9.7%, respectively, p = 0.001). Patients selected in the propensity-matching model showed similar results. Subgroup analysis also showed that HR was associated with better RFS than RFA for patients with 2 tumors, multifocal tumors located in the same lobe (Couinaud's segmentation) and segment (Takasaki's segmentation). Multivariate analysis revealed that 3 tumors, portal hypertension, and tumors located in different segments (Takasaki's segmentation) are independent predictors of poor prognosis in patients with multifocal tumors meeting the BCLC stage A. CONCLUSIONS: For patients with multifocal tumors meeting the BCLC stage A, HR may offer significantly better RFS than RFA, and HR may be considered as the first-line treatment option for those patients. PMID- 26362136 TI - Usefulness of Intraoperative Real-Time Tissue Elastography During Laparoscopic Hepatectomy. PMID- 26362137 TI - Preoperative Submucosal Injection of Carbon Nanoparticles Improves Lymph Node Staging Accuracy in Rectal Cancer after Neoadjuvant Chemoradiotherapy. AB - BACKGROUND: The aim of this study was to evaluate the association between the number of nodes harvested and the rate of node positivity, and to evaluate the effect of carbon nanoparticles (CNPs) in improving lymph node detection and staging accuracy in patients who received neoadjuvant chemoradiotherapy (NCRT) followed by curative resection. STUDY DESIGN: Between September 2008 and June 2014, 152 consecutive rectal cancer patients treated with NCRT and curative resection were included. Forty-five patients underwent preoperative submucosal injection of CNPs (CNP group); the other patients underwent surgery only (control group). The relationship between the number of lymph nodes harvested and the rate of node positivity was investigated. A comparison of the number of harvested lymph nodes and the node positivity rate between the 2 groups was also performed. The lymph nodes in the CNP group were analyzed in detail. RESULTS: The rate of node positivity increased gradually from 8.6% in patients with 1 to 5 nodes assessed to 37.8% in patients with 17 to 44 nodes assessed. The number of lymph nodes harvested was an independent risk factor for node positivity (p = 0.036). The mean number of lymph nodes retrieved in the CNP group was more than in the control group (21.1 vs 8.0, p = 0.000). The percentage of patients with positive lymph nodes was lower than in the control group (19.6% vs 35.6%, p = 0.037). In the CNP group, of 58 metastatic lymph nodes, 45 (77.6%) were dyed. Of 37 metastatic lymph nodes smaller than 5 mm, 33 (89.2%) were dyed. CONCLUSIONS: More precise oncologic prognosis assessment was provided for patients with rectal cancer after NCRT by increasing the number of lymph nodes counted using a dye tracing method, indicating that the use of CNPs is beneficial. PMID- 26362138 TI - Positionally-conserved but sequence-diverged: identification of long non-coding RNAs in the Brassicaceae and Cleomaceae. AB - BACKGROUND: Long non-coding RNAs (LncRNAs) have been identified as gene regulatory elements that influence the transcription of their neighbouring protein-coding genes. The discovery of LncRNAs in animals has stimulated genome wide scans for these elements across plant genomes. Recently, 6480 LincRNAs were putatively identified in Arabidopsis thaliana (Brassicaceae), however there is limited information on their conservation. RESULTS: Using a phylogenomics approach, we assessed the positional and sequence conservation of these LncRNAs by analyzing the genomes of the basal Brassicaceae species Aethionema arabicum and Tarenaya hassleriana of the sister-family Cleomaceae. Furthermore, we generated transcriptomes for another three Aethionema species and one other Cleomaceae species to validate their transcriptional activity. We show that a subset of LncRNAs are highly diverged at the nucleotide level, but conserved by position (syntenic). Positionally conserved LncRNAs that are expressed neighbour important developmental and physiological genes. Interestingly, >65 % of the positionally conserved LncRNAs are located within 2.5 Mb of telomeres in Arabidopsis thaliana chromosomes. CONCLUSION: These results highlight the importance of analysing not only sequence conservation, but also positional conservation of non-coding genetic elements in plants including LncRNAs. PMID- 26362139 TI - RELATIVE DISSOLUTION RATES OF RADIOACTIVE MATERIALS USED AT AWE. AB - A simple in vitro dissolution test was used to provide a semi-quantitative comparison of the relative dissolution rates of samples of radioactive materials used at Atomic Weapons Establishment in a lung fluid surrogate (Ringer's solution). A wide range of dissolution rates were observed for aged legacy actinides, freshly produced actinide alloys and actinides from waste management operations. PMID- 26362140 TI - DYNAMIC RESPONSE OF CCD ARRAY SPECTRORADIOMETERS. AB - A number of factors affect the measurements by charge coupled (CCD) array spectroradiometers, including stray light, dynamic response and ambient temperature. The departure from linearity was assessed for four CCD array spectroradiometers and linearity correction calculated with standard uncertainties error estimates. A fixed irradiance source supplemented with neutral density filters was used to allow tests to cover a full range of operational conditions. The dependence of the dynamic response on well depth and integration time was investigated. One spectroradiometer exhibited an accumulated departure from linearity of ~20 % near the top of the well; for others the departure from linearity was less pronounced. PMID- 26362141 TI - EGFR mutation status in Middle Eastern patients with non-squamous non-small cell lung carcinoma: A single institution experience. AB - BACKGROUND: Epidermal growth factor receptor (EGFR) represents an important molecular target in the treatment of lung adenocarcinomas; many anti-EGFR therapies are approved as first line and second-line treatment in patients having metastatic lung adenocarcinomas. The occurrence of this mutation varies in terms of race; it is around 10% in Caucasians and can reach 30% in Asians. Its prevalence in our Middle Eastern region is not well known. METHODS: Patients diagnosed with non-squamous non-small cell lung carcinomas between March 2013 and March 2015 were included. This study was conducted at Hotel-Dieu de France University Hospital, a tertiary medical center in Lebanon. EFGR mutations were analyzed using real time PCR technique on the Rotor-Gene Q using Scorpions and ARMS technologies. The following data was collected: the patients' characteristics (age, gender, smoking status, stage), the samples' characteristics (histology subtype, TTF-1 and Napsin A immunostainings, the site and the adequacy and the type of the sample), and the mutational EGFR status (presence and type of mutation). These variables were analyzed using SPSS 20. RESULTS: 201 patients were included. The mean age was 65.2 years [31-87]; 40.2% were females. 78.1% of the included patients were smokers or ex-smokers. 12.9% of patients had a localized disease, 17.4% a locally advanced disease and 69.7% a metastatic disease. Adenocarcinoma was the main histologic subtype found in 90.5% of patients, followed by large cell carcinoma (3.5%), adenosquamous carcinoma (3.0%) and non-small cell carcinoma not otherwise specified (3.0%). 11.9% of patients had an EGFR mutation: 48% of them presented a deletion on exon 19, 40.0% a L858R mutation on exon 21, 4.0% a G719X mutation in exon 18, 4.0% an insertion in exon 20, and 4% a T790M mutation in exon 20. The presence of an EGFR mutation was significantly associated with the female gender (two-third) (p<0.05) and the non-smoking status (two-third) (p<0.05). CONCLUSIONS: The prevalence of EGFR mutation (11.9%) detected in our Lebanese population is similar to that observed in the Caucasian population. This mutation is also significantly more frequent in females and non-smokers. PMID- 26362142 TI - The relative antimicrobial effect of blue 405 nm LED and blue 405 nm laser on methicillin-resistant Staphylococcus aureus in vitro. AB - It has long been argued that light from a laser diode is superior to light from a light-emitting diode (LED) in terms of its effect on biological tissues. In order to shed light on this ongoing debate, we compared the antimicrobial effect of light emitted from a 405-nm LED with that of a 405-nm laser on methicillin resistant Staphylococcus aureus (MRSA) at comparable fluences. We cultured 5 * 10(6) CFU/ml MRSA on tryptic soy agar and then irradiated culture plates once, twice, or thrice with either LED or laser light using 40, 54, 81, or 121 J/cm(2) fluence at 15-, 30-, or 240-min time interval between irradiation. Cultures were incubated immediately after irradiation at 37 degrees C for 24 h before imaging and counting remnant bacterial colonies. Regardless of the device used, LED or laser, irradiation at each fluence resulted in statistically significant bacterial growth suppression compared to non-irradiated controls (p < 0.0001). The antimicrobial effect of both light sources, LED and laser, was not statistically different at each fluence in 35 of the 36 experimental trials. Bacterial growth suppression achieved with either source of light increased with repeated irradiation, particularly at the 15- or 30-min treatment time interval. Thus, we conclude that the antimicrobial effect of 405-nm laser and 405-nm LED on MRSA is similar; neither has a superior antimicrobial effect when compared to the other. PMID- 26362143 TI - Design and Testing of Electric-Guided Delivery of Charged Particles to the Olfactory Region: Experimental and Numerical Studies. AB - Neurological drugs delivered to the olfactory region can enter the brain via olfactory pathways and bypass the blood-brain barrier. However, clinical applications of the direct nose-to-brain delivery are rare because of the extremely low olfactory doses using conventional nasal devices. This poor bioavailability is mainly caused by two factors: the complex nasal structure that traps particles in the anterior nose and the complete lack of control over particle motions after their release at the nostrils. In this study, the feasibility of electric-guided delivery to the olfactory region was tested in an anatomically accurate nasal airway model both experimentally and numerically. The nose replicas were prepared using 3-D printing and could be dissembled to reveal the local deposition patterns within the nasal cavity. A test platform was developed that included a dry powder charging system and a particle point-release nozzle. Numerical modeling was conducted using COMSOL and compared to corresponding experiments. Compared to conventional nasal devices, electric guidance of charged particles noticeably reduced particle losses in the anterior nose and increased depositions in the olfactory region. The thickness and relative permittivity of the wall were observed to affect the electric field strength and olfactory dosages. Consistent deposition patterns were obtained between experiments and numerical simulations in both 2-D and 3-D nose models. Two conceptual designs were proposed to generate, charge, and control aerosols. Results of this study indicate that it is feasible to use an electric field to control charged particles in the human nose. Both electric-guidance and point release of particles are essential to achieve targeted olfactory delivery. Future studies to refine the aerosol charging and release systems are needed for further enhancement of olfactory dosages. PMID- 26362144 TI - Bleeding Rate for Ultrasound-Guided Paracentesis in Thrombocytopenic Patients. AB - OBJECTIVES: The purpose of this study was to determine the rate of major bleeding complications for ultrasound-guided paracentesis performed in thrombocytopenic patients. METHODS: We retrospectively reviewed the electronic medical records of patients with platelet counts of less than 50,000/MUL who had ultrasound-guided paracenteses performed in the Department of Radiology without correcting preprocedural platelet transfusions between 2005 and 2011. Medical records were evaluated for evidence of major bleeding complications (grade 3 or higher as defined by the National Institutes of Health's Common Terminology Criteria for Adverse Events, version 4.03) and their clinical sequelae. Platelet count and bleeding complications were evaluated for an association, and a sensitivity analysis was performed to determine whether analysis of a control group of patients without thrombocytopenia would yield added confidence in this assessment. RESULTS: Among 304 procedures in 205 thrombocytopenic patients (69% male; mean age +/- SD, 56.6 +/- 11.9 years), the mean platelet count was 38,400 +/- 9300/MUL (range, 9000-49,000/MUL). Three major bleeding complications requiring red blood cell transfusion were observed in patients with platelet counts of 41,000 to 46,000/MUL, for a complication rate of 0.99% (95% confidence interval, 0.3%-2.9%). No patient required an additional procedure or died because of the bleeding complication. There was no association of platelet count with bleeding complications. The sensitivity analysis showed that further evaluation of patients with normal platelet counts would not add to the conclusion. CONCLUSIONS: The risk of major bleeding after ultrasound-guided paracentesis in thrombocytopenic patients is very low. In most patients, routine assessment of the preprocedural serum platelet concentration is not necessary, and correction of such an abnormal laboratory value is not indicated. PMID- 26362145 TI - Transcranial Parenchymal Sonographic Findings in Patients With Cerebral Small Vessel Disease: A Preliminary Study. AB - OBJECTIVES: Patients with cerebral small vessel disease often present with various motor, cognitive, and emotional changes, including gait disturbances, parkinsonism, and depression. Substantia nigra hyperechogenicity, brain stem raphe hypoechogenicity, ventricle diameters, and sonographic characteristics of other brain structures on transcranial sonography have been increasingly used as biomarkers in a range of neurologic diseases. We aimed to explore the frequency and clinical correlates of transcranial sonographic findings in symptomatic patients with small vessel disease. METHODS: In a cross-sectional study, neurologic, cognitive, and emotional statuses and transcranial sonographic and magnetic resonance imaging findings were compared between 102 patients with small vessel disease and 45 healthy age- and sex-matched control participants. RESULTS: Compared to healthy controls, small vessel disease cases had more frequent brain stem raphe hypoechogenicity (55.9% versus 11.1%; P < .0001), substantia nigra hyperechogenicity (30.4% versus 11.1%; P = .022), and enlarged third ventricles (P < .0001). Substantia nigra hyperechogenicity correlated with gait disturbances, extrapyramidal features, and cognitive impairment. Brain stem raphe hypoechogenicity was associated with the diagnosis of depression. Enlargement of the third and lateral ventricles was more frequent in patients with cognitive impairment. Pathologic substantia nigra hyperechogenicity and enlarged ventricles were associated with the severity of cerebral ischemic lesions. CONCLUSIONS: Transcranial sonography shows pathologic findings in a substantial number of patients with small vessel disease, probably reflecting disruption of frontostriatal pathways. PMID- 26362146 TI - Usefulness of Sonography in Evaluating Children Suspected of Malrotation: Comparison With an Upper Gastrointestinal Contrast Study. AB - OBJECTIVES: The purpose of this study was to prospectively evaluate the value of sonography in working up or ruling out malrotation by 3 sonographic features (inversion of the superior mesenteric artery and superior mesenteric vein, the whirlpool sign, and an intraperitoneal transverse duodenum) and comparing it with an upper gastrointestinal (GI) contrast study. METHODS: A total of 70 pediatric patients who underwent detailed abdominal sonography to rule out intestinal malrotation were included. Twenty-three of them also underwent an upper GI contrast study. Surgery or clinical follow-up was taken as the reference standard. Statistical analysis was performed with the chi(2) test. RESULTS: Twenty-three patients had a diagnosis of malrotation by surgical findings. With the combination of all 3 sonographic features, the sensitivity, specificity, and accuracy of sonography for determining malrotation were 100% (23 of 23), 97.8% (46 of 47), and 98.6% (69 of 70), respectively, whereas the sensitivity, specificity, and accuracy of the upper GI study were 40% (4 of 10), 64.3% (9 of 14), and 56.5% (13 of 23; P < .001). Combined anomalies in 2 patients and complications in 2 patients were also detected by sonography. CONCLUSIONS: By combining inversion of the superior mesenteric artery and superior mesenteric vein, the whirlpool sign, and an intraperitoneal transverse duodenum, sonography might be more valuable for accurately working up or ruling out pediatric malrotation than an upper GI contrast study. In addition, sonography could provide extra information, such as combined anomalies and intestinal necrosis, to help management. PMID- 26362147 TI - Evaluating Didactic Methods for Training Medical Students in the Use of Bedside Ultrasound for Clinical Practice at a Faculty of Medicine in Romania. AB - OBJECTIVES: Medical students' time is limited, so efficiency in medical education is valued. This research project aimed to determine the most effective means to teach bedside ultrasound to medical students in a 1-week training course. We hypothesized that the best method would include a combination of podcasts and hands-on teaching; therefore, there would be a statistically significant difference among the various methods of teaching. METHODS: Medical students were randomly assigned to 3 groups. All groups attended a 50-minute hands-on bedside ultrasound training session. Students in the first group attended a 50-minute live lecture before the hands-on session, whereas students in the second group watched a podcast that covered the same material as the live lecture. Students in the third group served as the control and only attended the hands-on sessions. Five topics were covered during the course: (1) introduction to ultrasound, (2) pulmonary ultrasound, (3) cardiac ultrasound, (4) hepatobiliary ultrasound, and (5) focused assessment with sonography for trauma. Students completed a 20 question pre- and post-training quiz that covered basic ultrasound principles. Students also conducted a focused assessment with sonography for trauma examination for the practical portion of their evaluation. RESULTS: Students' pre to post-training quiz scores increased from 33.6% to 72.6% correct in the lecture group (n = 21; P < .0001), from 40.7% to 75.5% correct in the podcast group (n = 20; P< .0001), and from 37.8% to 70.0% correct in the control group (n = 23; P< .0001). Data analysis of written and practical examination scores showed no significant differences among the groups [F(2,61) = 0.885; P = .418; F(2,60) = 1.739; P = .184, respectively]. CONCLUSIONS: These results suggest that all 3 methods are equally effective in teaching novice medical students basic ultrasound knowledge and skills. PMID- 26362148 TI - Internal Carotid Artery Hypoplasia: Role of Color-Coded Carotid Duplex Sonography. AB - OBJECTIVES: The purpose of this study was to determine the role of color-coded carotid duplex sonography for diagnosis of internal carotid artery hypoplasia. METHODS: We retrospectively reviewed 25,000 color-coded carotid duplex sonograms in our neurosonographic database to establish more diagnostic criteria for internal carotid artery hypoplasia. RESULTS: A definitive diagnosis of internal carotid artery hypoplasia was made in 9 patients. Diagnostic findings on color coded carotid duplex imaging include a long segmental small-caliber lumen (52% diameter) with markedly decreased flow (13% flow volume) in the affected internal carotid artery relative to the contralateral side but without intraluminal lesions. Indirect findings included markedly increased total flow volume (an increase of 133%) in both vertebral arteries, antegrade ipsilateral ophthalmic arterial flow, and a reduced vessel diameter with increased flow resistance in the ipsilateral common carotid artery. Ten patients with distal internal carotid artery dissection showed a similar color-coded duplex pattern, but the reductions in the internal and common carotid artery diameters and increase in collateral flow from the vertebral artery were less prominent than those in hypoplasia. The ipsilateral ophthalmic arterial flow was retrograde in 40% of patients with distal internal carotid artery dissection. In addition, thin-section axial and sagittal computed tomograms of the skull base could show the small diameter of the carotid canal in internal carotid artery hypoplasia and help distinguish hypoplasia from distal internal carotid artery dissection. CONCLUSIONS: Color coded carotid duplex sonography provides important clues for establishing a diagnosis of internal carotid artery hypoplasia. A hypoplastic carotid canal can be shown by thin-section axial and sagittal skull base computed tomography to confirm the final diagnosis. PMID- 26362149 TI - Sonographic Evaluation of the Plantar Heel in Asymptomatic Endurance Runners. AB - OBJECTIVES: The primary purpose of this investigation was to determine the prevalence and spectrum of asymptomatic sonographically determined structural changes in the plantar fascia and plantar heel pad among experienced runners without a history of heel pain. METHODS: Thirty-nine asymptomatic runners without a history of plantar heel pain were recruited. The following sonographic measures were recorded: power Doppler sonography in the plantar heel pad and plantar fascia, echo texture of the plantar heel pad, uncompressed heel pad thickness, compressed heel pad thickness, heel pad compressibility index, plantar fascia thickness, and plantar fascia echo texture. RESULTS: Doppler flow was shown in the plantar heel pads of 88% (68 of 77) of heels and 92% (36 of 39) of runners. Heel pad echo texture abnormalities were found in 86% (66 of 77) of heels and 97% (38 of 39) of runners. Mean values for right and left uncompressed heel pad thickness were 13.8 and 13.7 mm, respectively. The mean heel pad compressibility indices were 0.51 for the right heel and 0.53 for the left heel. Eight percent (6 of 77) of fat pads in 10% (4 of 39) of runners had abnormal compressibility indices. Doppler flow was present in the plantar fascia in 31% (24 of 77) of heels and 44% (17 of 39) of runners. The mean plantar fascia thicknesses were 3.78 mm for the right and 3.87 mm for the left. Forty-eight percent (37 of 77) of heels had an abnormal plantar fascia echo texture. CONCLUSIONS: At least 1 potentially abnormal sonographic finding was present in each heel of all asymptomatic runners in this study. Consequently, sonographic abnormalities in the plantar heel should be interpreted within the clinical context when evaluating runners. PMID- 26362150 TI - Parents' Translations of Child Gesture Facilitate Word Learning in Children with Autism, Down Syndrome and Typical Development. AB - Typically-developing (TD) children frequently refer to objects uniquely in gesture. Parents translate these gestures into words, facilitating children's acquisition of these words (Goldin-Meadow et al. in Dev Sci 10(6):778-785, 2007). We ask whether this pattern holds for children with autism (AU) and with Down syndrome (DS) who show delayed vocabulary development. We observed 23 children with AU, 23 with DS, and 23 TD children with their parents over a year. Children used gestures to indicate objects before labeling them and parents translated their gestures into words. Importantly, children benefited from this input, acquiring more words for the translated gestures than the not translated ones. Results highlight the role contingent parental input to child gesture plays in language development of children with developmental disorders. PMID- 26362151 TI - Prevalence of Autism Spectrum Disorder in Nurseries in Lebanon: A Cross Sectional Study. AB - In Lebanon, no estimate for autism prevalence exists. This cross-sectional study examines the prevalence of Autism spectrum disorder (ASD) in toddlers in nurseries in Beirut and Mount-Lebanon. The final sample included 998 toddlers (16 48 months) from 177 nurseries. We sent parents the Modified Checklist for Autism in Toddlers (M-CHAT) for screening, and a self-administered questionnaire (associated factors). We imputed missing M-CHAT data with successful answers. Since there were no follow-up interviews for the M-CHAT, we used the positive predictive value (0.058) from a large study for prevalence estimates. ASD prevalence was 1 in 66 children (comparable to US). Ratios were: male/female: 1.05; Beirut/Mount-Lebanon: 1.2. Using a more representative sample and ascertaining results are needed for better prevalence estimates in Lebanon. PMID- 26362152 TI - Relationship of the Acoustic Startle Response and Its Modulation to Emotional and Behavioral Problems in Typical Development Children and Those with Autism Spectrum Disorders. AB - Auditory hyper-reactivity is a common sensory-perceptual abnormality in autism spectrum disorders (ASD), which interrupts behavioral adaptation. We investigated acoustic startle response (ASR) modulations in 17 children with ASD and 27 with typical development (TD). Compared to TD, children with ASD had larger ASR magnitude to weak stimuli and more prolonged peak startle-latency. We could not find significant difference of prepulse inhibition (PPI) or habituation in ASD children compared to TD. However, habituation and PPI at 70-dB prepulses were negatively related to several subscales of Social Responsiveness Scale and the Strengths and Difficulties Questionnaire, when considering all children. Comprehensive investigation of ASR and its modulation might increase understanding of the neurophysiological impairments underlying ASD and other mental health problems in children. PMID- 26362153 TI - Mass spectrometric analysis of products of metabolic glycan engineering with azido-modification of sialic acids. AB - Metabolic engineering of glycans present on antibodies and other glycoproteins is becoming an interesting research area for improving our understanding of the glycome. With knowledge of the sialic acid biosynthetic pathways, the experiments described in this report are based on a published procedure involving the addition of a synthesized azido-mannosamine sugar into cell culture media and evaluation of downstream expression as azido-sialic acid. This unique bioorthogonal sugar has the potential for a variety of "click chemistry" reactions through the azide linkage, which allow for it to be isolated and quantified given the choice of label. In this report, mass spectrometry was used to investigate and optimize the cellular absorption of peracetylated N azidoacetylmannosamine (Ac4ManNAz) to form N-azidoacetylneuraminic acid (SiaNAz) in a Chinese hamster ovary (CHO) cell line transiently expressing a double mutant trastuzumab (TZMm2), human galactosyltransferase 1 (GT), and human alpha-2,6 sialyltransferase (ST6). This in vivo approach is compared to in vitro enzymatic addition SiaNAz onto TZMm2 using soluble beta-galactosamide alpha-2,6 sialyltransferase 1 and CMP-SiaNAz as donor. The in vivo results suggest that for this mAb, concentrations above 100 MUM of Ac4ManNAz are necessary to allow for observation of terminal SiaNAz on tryptic peptides of TZMm2 by matrix-assisted laser desorption ionization (MALDI) mass spectrometry. This is further confirmed by a parallel study on the production of EG2-hFc monoclonal antibody (Zhang J et al. Prot Expr Purific 65(1); 77-82, 2009) in the presence of increasing concentrations of Ac4ManNAz. PMID- 26362154 TI - Determination of reduced homocysteine in human serum by elemental labelling and liquid chromatography with ICP-MS and ESI-MS detection. AB - Analytical methods allowing sensitive determination of reduced homocysteine (rHcy), one of the so-called biothiols, in human serum is a topic of growing interest due to its close relation to several human disorders, mainly cardiovascular diseases. Although most widely used analytical strategies to determine total Hcy involve derivatization by means of fluorescent labels, this work proposes the use of ebselen, a Se-containing labelling agent to derivatize the reactive sulfhydryl group of the Hcy molecule in its "free" reduced form, which is more likely to play different roles in disease pathogenesis. Optimization of the derivatization and separation conditions by high-performance liquid chromatography (HPLC) to isolate the excess of derivatizing reagent is carried out here using UV/VIS detection. Further, the study of the Se labelling reaction by electrospray ionization tandem mass spectrometry (ESI-MS/MS) provides a stoichiometry of the derivative of 1:1. The main advantage of using ebselen as a labelling agent is the presence of the Se atom in the molecule that allows the use of inductively coupled plasma mass spectrometry (ICP-MS) as a sensitive and selective Se detector. The coupling of HPLC with ICP-MS provided excellent features for the determination of Se-derivatized rHcy (detection limit of 9.6 nM) in real samples. Quantification was accomplished by using post-column isotope dilution (ID) of Se in serum samples, after precipitation of the main serum proteins. Quantitative results for "free" rHcy turned out to be around 0.18-0.22 MUM in serum samples from healthy individuals that could be directly analyzed without sample preconcentration. PMID- 26362155 TI - Simultaneous quantification of labeled (2)H5-glycerol, (13)C6-glucose, and endogenous D-glucose in mouse plasma using liquid chromatography tandem mass spectrometry. AB - Monitoring the level of glucose and glycerol or their labeled derivatives in biological fluid for kinetic studies has always been challenging, especially in mice, because of the limited volume in addition to the complexity of plasma. For such application, we developed a simple, fast, and sensitive method for the simultaneous measurement of absolute concentrations of labeled (2)H5-glycerol and (13)C6-glucose as well as endogenous D-glucose using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). In our study, 15.0 MUL of mouse plasma was processed by a one-step protein precipitation, followed by LC-MS/MS analysis. The quantification of the analytes was carried out by monitoring the product ion scan of their corresponding deprotonated molecular ions and constructing the extracted ion fragmentogram by choosing a specific product ion for each analyte (equivalent to precursor ion to product ion transitions). The limit of detection (LOD) was evaluated to be 1.0 MUM for both (2)H5-glycerol and (13)C6-glucose, and the limit of quantitation (LOQ) was observed to be 5.0 MUM for both (2)H5-glycerol and (13)C6-glucose in diluted mice plasma that corresponds to 50 MUM in plasma or 4.60 and 9.01 mg/dL of glycerol and glucose in plasma, respectively. The extraction recoveries are 81.9 % (CV = 8.1 %) for (2)H5 glycerol and 26.2 % (CV = 13.6 %) for (13)C6-glucose. PMID- 26362156 TI - Orthogonal analysis of functional gold nanoparticles for biomedical applications. AB - We report a comprehensive strategy based on implementation of orthogonal measurement techniques to provide critical and verifiable material characteristics for functionalized gold nanoparticles (AuNPs) used in biomedical applications. Samples were analyzed before and after ~50 months of cold storage (~4 degrees C). Biomedical applications require long-term storage at cold temperatures, which could have an impact on AuNP therapeutics. Thiolated polyethylene glycol (SH-PEG)-conjugated AuNPs with different terminal groups (methyl-, carboxylic-, and amine-) were chosen as a model system due to their high relevancy in biomedical applications. Electrospray-differential mobility analysis, asymmetric-flow field flow fractionation, transmission electron microscopy, scanning electron microscopy, atomic force microscopy, inductively coupled plasma mass spectrometry, and small-angle X-ray scattering were employed to provide both complementary and orthogonal information on (1) particle size and size distribution, (2) particle concentrations, (3) molecular conjugation properties (i.e., conformation and surface packing density), and (4) colloidal stability. Results show that SH-PEGs were conjugated on the surface of AuNPs to form a brush-like polymer corona. The surface packing density of SH-PEG was ~0.42 nm(-2) for the methyl-PEG-SH AuNPs, ~0.26 nm(-2) for the amine-SH-PEG AuNPs, and ~0.18 nm(-2) for the carboxylic-PEG-SH AuNPs before cold storage, approximately 10 % of its theoretical maximum value. The conformation of surface-bound SH-PEGs was then estimated to be in an intermediate state between brush-like and random coiled, based on the measured thicknesses in liquid and in dry states. By analyzing the change in particle size distribution and number concentration in suspension following cold storage, the long term colloidal stability of AuNPs was shown to be significantly improved via functionalization with SH-PEG, especially in the case of methyl-PEG-SH and carboxylic-PEG-SH (i.e., we estimate that >80 % of SH-PEG5K remained on the surface of AuNPs during storage). The work described here provides a generic strategy to track and analyze the material properties of functional AuNPs intended for biomedical applications, and highlights the importance of a multi-technique analysis. The effects of long term storage on the physical state of the particles, and on the stability of the ligand-AuNP conjugates, are employed to demonstrate the capacity of this approach to address critical issues relevant to clinical applications. PMID- 26362157 TI - Raman4Clinics: the prospects of Raman-based methods for clinical application. PMID- 26362158 TI - Unraveling the in vitro and in vivo metabolism of diacetoxyscirpenol in various animal species and human using ultrahigh-performance liquid chromatography quadrupole/time-of-flight hybrid mass spectrometry. AB - Diacetoxyscirpenol (DAS), a Fusarium mycotoxin belonging to the trichothecene type A mycotoxins, is able to contaminate food and feed worldwide. Only limited information is available regarding the metabolism of DAS. The present study used ultrahigh-performance liquid chromatography-quadrupole/time-of-flight hybrid mass spectrometry (UHPLC-Q/TOF) to investigate the in vitro phase I and II metabolism of DAS by rat, chicken, swine, goat, cow, and human liver microsomes. An extensive metabolization profile of DAS has been observed. A total of seven phase I and three phase II metabolites of DAS were detected. Among the identified molecules, four phase I metabolites (8beta-hydroxy-DAS, neosolaniol, 7-hydroxy DAS, and its epimer) and two phase II metabolites (4-deacetyl-DAS-3-glucuronic acid and 4-deacetyl-DAS-4-glucuronic acid) were identified for the first time. These results indicate that the major metabolic pathways of DAS in vitro were hydrolyzation (M1-M3), hydroxylation (M4-M7), and conjugation (M8-M10). Qualitative differences in phase I and II metabolic profiles of DAS between the five animal species and human were observed. 4-Deacetyl-DAS was the primary metabolite from liver microsomes of all species, especially human. The in vivo metabolism of DAS in rats and chickens after oral administration of DAS was also investigated and compared. The major metabolites for rats and chickens were 4 deacetyl-DAS and 7-hydroxy-DAS. These results will help to gain a more detailed insight into the metabolism and toxicity of DAS among different animal species and human. Graphical Abstract The metabolism of diacetoxyscirpenol in farm animals and human. PMID- 26362159 TI - Clinical validation of surface-enhanced Raman scattering-based immunoassays in the early diagnosis of rheumatoid arthritis. AB - We assessed the clinical feasibility of conducting immunoassays based on surface enhanced Raman scattering (SERS) in the early diagnosis of rheumatoid arthritis (RA). An autoantibody against citrullinated peptide (anti-CCP) was used as a biomarker, magnetic beads conjugated with CCP were used as substrates, and the SERS nanotags were comprised of anti-human IgG-conjugated hollow gold nanospheres (HGNs). We were able to determine the anti-CCP serum levels successfully by observing the distinctive Raman intensities corresponding to the SERS nanotags. At high concentrations of anti-CCP (>25 U/mL), the results obtained from the SERS assay confirmed those obtained via an ELISA-based assay. Nevertheless, quantitation via our SERS-based assay is significantly more accurate at low concentrations (<25 U/mL). In this study, we compared the results of an anti-CCP assay of 74 clinical blood samples obtained from the SERS-based assay to that of a commercial ELISA kit. The results of the anti-CCP-positive group (n = 31, >25 U/mL) revealed a good correlation between the ELISA and SERS-based assays. However, in the anti-CCP-negative group (n = 43, <25 U/mL), the SERS-based assay was shown to be more reproducible. Accordingly, we suggest that SERS-based assays are novel and potentially useful tools in the early diagnosis of RA. PMID- 26362160 TI - Horizontal Gene Transfer of the Non-ribosomal Peptide Synthetase Gene Among Endophytic and Epiphytic Bacteria Associated with Ethnomedicinal Plants. AB - This study genetically screened endophytic and epiphytic bacteria associated with ethnomedicinal plants for the presence of the non-ribosomal peptide synthetase (NRPS) gene and identified horizontal gene transfer (HGT) of the NRPS gene between the bacterial species. NRPSs are large multimodular enzymes that synthesize a wide range of biologically active natural compounds that are pharmacologically important. Twenty-nine plant-associated culturable bacteria were screened for the presence of the NRPS gene, of which seven bacterial NRPS gene fragments were successfully detected. According to our findings the presence of NRPS gene among the isolates does not always equate to their antagonistic ability. Phylogenetic analysis of the NRPS and 16S rRNA-encoding genes was used to predict HGT that may have occurred during gene evolution. The occurrence of HGT was demonstrated in the isolates (one inter-phylum and four intra-phyla) and was supported by phylogenetic analysis, mol% G+C content, and tetranucleotide usage pattern and codon usage frequency. Among the four intra-phyla HGT, one isolate showed inter-class HGT and three other isolates showed intra-class HGT. PMID- 26362161 TI - Comparison of Two Concentration Methods for the Molecular Detection of Enteroviruses in Raw and Treated Sewage. AB - Human enteric viruses are a major causative agent of emerging waterborne diseases and constitute a serious public health concern. Environmental contamination occurs through discharge of waste materials from infected persons. Methods for viral detection should be developed to detect low infective dose of enteric viruses in environment. In this study, we aimed at comparing two concentration methods for the detection of naturally occurring enteroviruses in raw and treated sewage. In the first method, polyethylene glycol is used to concentrate viral particles from the collected samples. The second method is based on ultracentrifugation of viral particles at high speed (110,000*g). Genomes of enteroviruses were quantified by the quantitative real-time PCR method in raw and treated sewage samples. PEG-based method yielded higher genomic copies of enteric viruses (with an average of 5.9 log10 genomic copies/100 mL) when applied to raw sewage samples. While the ultracentrifugation assay in the second method decreases genomic copies number (with an average of 5.4 log10 genomic copies/100 mL). The recovery differences between the two methods were not significant when applied to clean samples (treated sewage). This could be explained by the presence of inhibitors, which interfere with qRT-PCR, in less quantity comparatively to raw sewage. PEG-based method would be more accurate for samples with high-organic matter load. This report emphasizes the importance of matrices nature on the recovery of enteroviruses from sewage samples. This should be taken into consideration for establishing standardized virological assays to ensure the virological quality control of discharged water in environment. PMID- 26362162 TI - Erratum to: Development of a consensus-base list of criteria for prescribing medication in a pediatric population. PMID- 26362163 TI - A critical appraisal of statistical pitfalls and clinical relevance of meta analysis involving hepatitis C virus and sofosbuvir. PMID- 26362164 TI - Using Mental Health Outreach Teams in the Emergency Department to Improve Engagement in Treatment. AB - Engagement in treatment for a person having a behavioral health crisis is critical to fully address the concerns of the individual as well as to prevent future crises. This study explored the benefits of establishing outreach visits from a local community mental health provider to psychiatric patients in an emergency department. Using retrospective analysis of data collected by a local mental health agency, the effect of receiving face to face contact in the emergency room with a community mental health worker (and/or telephone follow up) was compared to no outreach interaction. The effect of this intervention was a significant increase in initial appointment attendance at the local mental health clinic in the aftermath of a psychiatric crisis. Community mental health services provided in partnership with community emergency departments may improve patient engagement in aftercare and consequently help alleviate future behavioral health crises as well as return visits to the emergency department. PMID- 26362165 TI - Lacidipine self-nanoemulsifying drug delivery system for the enhancement of oral bioavailability. AB - Low bioavailability of Lacidipine (LD), an calcium channel blocker pose many challenges in the treatment of hypertension. The objective of this study was to formulate and characterize LD self-nanoemulsifying drug delivery systems (SNEDDS) to improve oral bioavailability of the drug. Formulations were evaluated for globule size, surface morphology, emulsification time, cloud point, drug content, in vitro dissolution, ex vivo permeation, stability and oral bioavailability studies. Captex 810D, TPGS, Tween-60, Transcutol P and PEG 400 was selected based on the solubility study results. The optimized SNEDDS readily gets nanoemulsified at 37 degrees C with droplet size of 41 nm when mixed with 200 times of its water. Transmission electron microscope photographs confirmed the spherical shape of the globules. In vitro dissolution of SNEDDS showed more than 80% of drug release within 15 min. The ex vivo permeation of LD from SNEDDS is 4.8- and 9 fold higher compared to pure drug in the absence and presence of verapamil respectively. The stability study of the SNEDDS confirmed no environmental effect on the physical nature and drug content. Oral bioavailability of SNEDDS is 2.5 times higher than marketed tablet. The results suggest that, the SNEDDS formulation can be used as a possible alternative for the traditional oral formulations of LD to improve its oral bioavailability. PMID- 26362166 TI - Effects of Female fruit-marking Pheromones on Oviposition, Mating, and Male Behavior in the Neotropical Species Rhagoletis conversa Brethes and Rhagoletis brncici Frias (Diptera: Tephritidae). AB - Sex pheromones produced by females of Rhagoletis conversa Brethes and Rhagoletis brncici Frias are deposited on the surface of fruits after the eggs are laid. These pheromones repel other females, preventing repeated oviposition on the same fruit. They also attract males, thus assisting mating. Observations were made on wild populations, and cross-species behavioral tests were performed on males. The pheromone released by females was significantly more attractive for males of the same species. The two species showed remarkable differences in mating behavior, in the duration of oviposition, and in the number of circuits made around the fruit after eggs were laid. A morphological analysis of flies collected from their respective host plants indicated great host fidelity and the reproductive isolation of the two species. Possibly, the specific male-arresting effect of this pheromone was important for the sympatric speciation and evolution of these sibling species. PMID- 26362168 TI - Toward Development of Enhanced Preventive Interventions for HIV Sexual Risk among Alcohol-Using Populations: Confronting the 'Mere Pause from Thinking'. AB - The papers in this issue detail state-of-the science knowledge regarding the role of alcohol use in HIV/AIDS risk, as well as offer suggestions for ways forward for behavioral HIV prevention for at-risk alcohol-using populations. In light of recent evidence suggesting that the anticipated uptake of the newer biomedical HIV prevention approaches, prominently including pre-exposure prophylaxis, has been stalled owing to a host of barriers, it has become ever more clear that behavioral prevention avenues must continue to receive due consideration as a viable HIV/AIDS prevention approach. The papers collected here make a valuable contribution to "combination prevention" efforts to curb HIV spread. PMID- 26362167 TI - A Randomized Controlled Trial of Personalized Text Message Reminders to Promote Medication Adherence Among HIV-Positive Adolescents and Young Adults. AB - HIV-positive adolescents and young adults often experience suboptimal medication adherence, yet few interventions to improve adherence in this group have shown evidence of efficacy. We conducted a randomized trial of a two-way, personalized daily text messaging intervention to improve adherence to antiretroviral therapy (ART) among N = 105 poorly adherent HIV-positive adolescents and young adults, ages 16-29. Adherence to ART was assessed via self-reported visual analogue scale (VAS; 0-100 %) at 3 and 6-months for mean adherence level and proportion >=90 % adherent. The average effect estimate over the 6-month intervention period was significant for >=90 % adherence (OR = 2.12, 95 % CI 1.01-4.45, p < .05) and maintained at 12-months (6 months post-intervention). Satisfaction scores for the intervention were very high. These results suggest both feasibility and initial efficacy of this approach. Given study limitations, additional testing of this intervention as part of a larger clinical trial with objective and/or clinical outcome measures of adherence is warranted. PMID- 26362169 TI - Insulin gene VNTR polymorphisms -2221MspI and -23HphI are associated with type 1 diabetes and latent autoimmune diabetes in adults: a meta-analysis. AB - AIMS: A variable number of tandem repeat (VNTRs) region in the insulin gene (INS) possibly influences the progression of type 1 diabetes (T1D) and latent autoimmune diabetes in adults (LADA). However, effects of INS VNTR polymorphisms in these contexts remain inconclusive. METHODS: We performed a systematic review of work on the INS VNTR -2221MspI and -23HphI polymorphisms to estimate the overall effects thereof on disease susceptibility; we included 17,498 T1D patients and 24,437 controls, and 1960 LADA patients and 5583 controls. RESULTS: For T1D, the C allele at -2221MspI and the A allele at -23HphI were associated with estimated relative risks of 2.13 (95 % CI 1.94, 2.35) and 0.46 (95 % CI 0.44, 0.48), which contributed to absolute increases of 46.76 and 46.98 % in the risk of all T1D, respectively. The estimated lambda values were 0.44 and 0.42, respectively, suggesting that a co-dominant model most likely explained the effects of -2221MspI and -23HphI on T1D. For -23HphI, the A allele carried an estimated relative risk of 0.55 (95 % CI 0.50, 0.61) for LADA and increased the risk of all LADA by 36.94 %. The lambda value was 0.43, suggesting that a co dominant model most likely explained the effect of -23HphI on LADA. CONCLUSIONS: Our results support the existence of associations of INS with T1D and LADA. PMID- 26362170 TI - Polio revisited: reviving knowledge and skills to meet the challenge of resurgence. AB - PURPOSE: To date, polio has not been eradicated and there appears to be a resurgence of the disease. Hence, there is a need to revive decision-making skills to treat the effects of polio. METHODS: Here, we outline the aspects of treatment of paralysis following polio based on the literature and personal experience of the authors. The surgical treatment of the lower and upper extremities and the spine have been reviewed. The scope of bracing of the lower limb has been defined. RESULTS: The effects of polio can be mitigated by judicious correction of deformities, restoration of muscle balance, stabilising unstable joints and compensating for limb length inequality. CONCLUSIONS: As polio has not been eradicated and there is a risk of resurgence of the disease, paediatric orthopaedic surgeons need to be prepared to deal with fresh cases of polio. Revival of old techniques for managing the effects of paralysis following polio is needed. PMID- 26362171 TI - Caput valgum associated with developmental dysplasia of the hip: management by transphyseal screw fixation. AB - PURPOSE: A late finding of some hips treated for developmental dysplasia of the hip (DDH) is a growth disturbance of the lateral proximal femoral physis, which results in caput valgum and possibly osteoarthritis. Current treatment options include complete epiphysiodesis of the proximal femoral physis or a corrective proximal femoral osteotomy. Alternatively, a transphyseal screw through the inferomedial proximal femoral physis that preserves superolateral growth might improve this deformity. METHODS: This study evaluates the effect of such a transphyseal screw on both femoral and acetabular development in patients with caput valgum following open treatment of DDH. These patients were followed clinically and radiographically until skeletal maturity. Preoperative and postoperative radiographs were assessed, measuring the proximal femoral physeal orientation (PFPO), the head-shaft angle (HSA), Sharp's angle and the center edge angle of Wiberg (CE angle). RESULTS: Thirteen hips of 11 consecutive patients were followed prospectively. The age at the time of transphyseal screw placement was between 5 and 14 years. The mean improvement of the PFPO and HSA was 14 degrees (p < 0.01) and 11 degrees (p < 0.001), respectively. The mean improvement of Sharp's angle and CE angle was 4.7 degrees (p < 0.01) and 5.8 degrees (p < 0.02), respectively. Five patients underwent screw revision. CONCLUSIONS: A transphyseal screw across the proximal femoral physis improved the proximal femur and acetabular geometry. PMID- 26362172 TI - Cost-effectiveness of high-dose versus standard-dose inactivated influenza vaccine in adults aged 65 years and older: an economic evaluation of data from a randomised controlled trial. AB - BACKGROUND: Adults aged 65 years and older account for most seasonal influenza related hospital admissions and deaths. Findings from the randomised controlled FIM12 study showed that high-dose inactivated influenza vaccine is more effective than standard-dose vaccine for prevention of laboratory-confirmed influenza in this age group. We aimed to assess the economic impact of high-dose versus standard-dose influenza vaccine in participants in the FIM12 study population. METHODS: The FIM12 study was a head-to-head randomised controlled trial in which 31,989 participants aged 65 years and older were randomly assigned (1:1) to receive either high-dose or standard-dose trivalent inactivated influenza vaccine over two influenza seasons (2011-12 and 2012-13). Data for health-care resource consumption obtained in the FIM12 study were summarised across vaccine groups. Unit costs obtained from standard US cost sources were applied to each resource item, including to the vaccines (high dose US$31.82, standard dose $12.04). Clinical illness data were mapped to existing quality-of-life data. The time horizon was one influenza season; however, quality-adjusted life-years (QALYs) lost due to death during the study were calculated over a lifetime. We calculated incremental cost-effectiveness ratios (ICERs) for high-dose versus standard-dose vaccine and used QALYs as an outcome in the cost-utility analysis. We undertook a probabilistic sensitivity analysis using bootstrapping to explore the effect of statistical uncertainty on the study results. FINDINGS: Mean per-participant medical costs were lower in the high-dose vaccine group ($1376.72 [SD 6857.59]) than in the standard-dose group ($1492.64 [7447.14]; difference -$115.92 [95% CI 264.18 to 35.48]). Mean societal costs were likewise lower in the high-dose versus the standard-dose group ($1506.48 [SD 7305.19] vs $1634.50 [7952.99]; difference -$128.02 [95% CI -286.89 to 33.30]). Hospital admissions contributed 95% of the total health-care-payer cost and 87% of the total societal costs. The mean per-participant number of hospital admissions was 0.0937 (SD 0.3644) in the high-dose group and 0.1017 (0.3708) in the standard-dose group (difference 0.0080, 95% CI -0.0160 to -0.0003). The high-dose vaccine provided a gain in QALYs (mean 8.1502 QALYs gained per participant [SD 0.5693]) compared with the standard-dose vaccine (8.1499 QALYs [0.5697]) and, due to cost savings, dominated standard-dose vaccine in the cost-utility analysis. The probabilistic sensitivity analysis showed that the high-dose vaccine is 93% likely to be cost saving. INTERPRETATION: High-dose trivalent inactivated influenza vaccine is a less costly and more effective alternative to the standard-dose vaccine, driven by a reduction in the number of hospital admissions. These findings are relevant to US health-care beneficiaries, providers, payers, and recommending bodies, especially those seeking to improve outcomes while containing costs. FUNDING: Sanofi Pasteur. PMID- 26362173 TI - High-dose influenza vaccines make economic sense for older people. PMID- 26362175 TI - Metals as radio-enhancers in oncology: The industry perspective. AB - Radio-enhancers, metal-based nanosized agents, could play a key role in oncology. They may unlock the potential of radiotherapy by enhancing the radiation dose deposit within tumors when the ionizing radiation source is 'on', while exhibiting chemically inert behavior in cellular and subcellular systems when the radiation beam is 'off'. Important decision points support the development of these new type of therapeutic agents originated from nanotechnology. Here, we discuss from an industry perspective, the interest of developing radio-enhancer agents to improve tumor control, the relevance of nanotechnology to achieve adequate therapeutic attributes, and present some considerations for their development in oncology. PMID- 26362174 TI - Challenges and key research questions for yaws eradication. AB - Yaws is endemic in west Africa, southeast Asia, and the Pacific region. To eradicate yaws by 2020, WHO has launched a campaign of mass treatment with azithromycin. Progress has been made towards achievement of this ambitious goal, including the validation of point-of-care and molecular diagnostic tests and piloting of the strategy in several countries, including Ghana, Vanuatu, and Papua New Guinea. Gaps in knowledge need to be addressed to allow refinement of the eradication strategy. Studies exploring determinants of the spatial distribution of yaws are needed to help with the completion of baseline mapping. The finding that Haemophilus ducreyi causes lesions similar to yaws is particularly important and further work is needed to assess the effect of azithromycin on these lesions. The integration of diagnostic tests into different stages of the eradication campaign needs investigation. Finally, studies must be done to inform the optimum mass-treatment strategy for sustainable interruption of transmission. PMID- 26362176 TI - Doxorubicin-loaded magnetic nanoparticle clusters for chemo-photothermal treatment of the prostate cancer cell line PC3. AB - In addition to the conventional cancer treatment such as radiotherapy, chemotherapy and surgical management, nanomedicine-based approaches have attracted widespread attention in recent years. In this paper, a promising nanocarrier, magnetic nanoparticle clusters (MNCs) as porous materials which provided enough room on the surface, was developed for loading chemotherapeutic agent of doxorubicin (DOX). Moreover, MNCs are a good near-infrared (NIR) photothermal mediator. Thus, MNCs have great potential both in photothermal therapy (PTT) and drug delivery for chemo-photothermal therapy of cancer. We firstly explored the destruction of prostate cancer in vitro by the combination of PTT and chemotherapy using DOX@MNCs. Upon NIR irradiation at 808 nm, more cancer cells were killed when PC3 cells incubated with DOX@MNCs, owing to both MNCs-mediated photothermal ablation and cytotoxicity of light-triggered DOX release. Compared with PTT or chemotherapy alone, the chemo-photothermal therapy by DOX@MNCs showed a synergistically higher therapeutic efficacy. PMID- 26362177 TI - Hyaluronan-induced VEGF-C promotes fibrosis-induced lymphangiogenesis via Toll like receptor 4-dependent signal pathway. AB - Hyaluronan (HA), a component of the extracellular matrix, modulates cellular behavior including angiogenesis. However, little is known about the effect of HA on lymphangiogenesis in fibrosis model. In this study, we investigated the roles of HA in lymphangiogenesis of unilateral ureteral obstruction (UUO). We found that HA cooperated synergistically with vascular endothelial cell growth factor-C to stimulate capillary-like tube formation and increase migration of cells in a haptotaxis assay. Accumulation of HA in the cortical interstitial space was positively correlated with the number of lymphatic vessels after UUO. Depletion of macrophages with clodronate decreased UUO-induced HA accumulation and lymphangiogenesis. Additionally, hyaluronan synthase (HAS) mRNA expression and HA production were increased in bone marrow-derived macrophages upon stimulation with TGF-beta1. Transfer of mHAS2 and mHAS3 knock-down CD11b-positive macrophages to SCID mice resulted in a partial decrease in UUO-induced lymphangiogenesis. HA increased expression of vascular endothelial cell growth factor-C in macrophages. Vascular endothelial cell growth factor-C expression and LYVE-1-positive lymphatic area was significantly lower in the UUO-kidney from TLR4 null mice than that from TLR4 wild-type mice. Collectively, these results suggest that HA increases lymphangiogenesis in renal fibrosis model and also stimulates vascular endothelial cell growth factor-C production from macrophages through Toll-like receptor 4-dependent signal pathway. PMID- 26362178 TI - Presence of an amino acid residue at position 619 required for the function of YidC in Rhodobacter sphaeroides. AB - YidC, the bacterial homologous protein of Oxa1 and Alb3, could insert membrane proteins into the membrane. Rhodobacter sphaeroides is a kind of photobacteria with abundant intracytoplasmic membranes. In this study, the functions of R. sphaeroides YidC and its C-terminus were investigated in the Escherichia coli YidC gene depletion strain FTL10. The results showed that RS_YidC could complement the growth of the strain FTL10, but the RS_YidC last 5 residues (619 623, KKRKP) deletion mutant could not. Interestingly, the site-directed RS_YidC mutants of any one or all of these 5 residues were still active. The deletion mutant of the last 4 residues and even the last 4 residues deletion mutant with substitution of the Ala or Glu for Lys619 still had sufficient activity to complement the growth of the strain FTL10. These results indicated that the length of the C-terminus of Rs_YidC is more important for its function than the amino acid composition or the charges of it, and the presence of an amino acid residue at position 619 is required for Rs_YidC function in E. coli. Our result also suggests that Rs_YidC may function differently as compared to its homologs. PMID- 26362179 TI - FGF1-FGFR1 axis promotes tongue squamous cell carcinoma (TSCC) metastasis through epithelial-mesenchymal transition (EMT). AB - Increasing evidences suggest a close association between tumor metastasis and the inflammatory factors secreted by tumor microenvironment. It has been reported that epithelial mesenchymal-transition (EMT) plays a significant role during multiple types of tumor metastasis and progression induced by inflammatory factor from tumor microenvironment. Previous researches implied that fibroblast growth factor 1 (FGF1) can promote tumor progression and cause poor prognosis in several types of malignant tumors via interacting with its receptor fibroblast growth factor receptor 1 (FGFR1). However, the effects of FGF1-FGFR1 on tongue squamous cell carcinoma (TSCC) are not yet completely understood. In the present study, we evaluated the effects and function of FGF1-FGFR1 axis on TSCC metastasis. In addition, we investigated whether the EMT pathway is involved in these effects, thus modulating the TSCC progression. The expression of FGFR1 was measured both in tongue cancer cell lines and tissues by qRT-PCR and western blot. We found that FGFR1 was up-regulated in TSCC tissues compared to non-neoplastic tongue tissues. Additionally, overexpression of FGFR1 is positively associated with poor differentiation and metastasis potential. Furthermore, the function of FGF1-FGFR1 was examined in TSCC cell line. The results implied that FGF1 can obviously promote Cal27 cells migration and invasion abilities through FGFR1, while the motile and invasive capabilities can be severely attenuated when knockdown the expression of FGFR1 by specific siRNAs. Further investigation results show that FGF1-FGFR1 axis promotes TSCC metastasis by modulating EMT pathway. However, this effect can be inhibited by blocking the FGF1-FGFR1 axis using FGFR1 specific siRNAs. In conclusion, our findings of the present study provide the evidences that FGF1-FGFR1 axis promotes the TSCC metastasis through the EMT pathway. PMID- 26362180 TI - Sugarcane Elongin C is involved in infection by sugarcane mosaic disease pathogens. AB - Sugarcane (Saccharum sp. hybrid) provides the main source of sugar for humans. Sugarcane mosaic disease (SMD) is a major threat to sugarcane production. Currently, control of SMD is mainly dependent on breeding resistant cultivars through hybridization, which is time-consuming. Understanding the mechanism of viral infection may facilitate novel strategies to breed cultivars resistant to SMD and to control the disease. In this study, a wide interaction was detected between the viral VPg protein and host proteins. Several genes were screened from sugarcane cDNA library that could interact with Sugarcane streak mosaic virus VPg, including SceIF4E1 and ScELC. ScELC was predicted to be a cytoplasmic protein, but subcellular localization analysis showed it was distributed both in cytoplasmic and nuclear, and interactions were also detected between ScELC and VPg of SCMV or SrMV that reveal ScELC was widely used in the SMD pathogen infection process. ScELC and VPgs interacted in the nucleus, and may function to enhance the viral transcription rate. ScELC also interacted with SceIF4E2 both in the cytoplasm and nucleus, but not with SceIF4E1 and SceIF4E3. These results suggest that ScELC may be essential for the function of SceIF4E2, an isomer of eIF4E. PMID- 26362181 TI - DNA visualization in single molecule studies carried out with optical tweezers: Covalent versus non-covalent attachment of fluorophores. AB - In this study, we investigated the use of the covalent attachment of fluorescent dyes to double-stranded DNA (dsDNA) stretched between particles using optical tweezers (OT) and compared the mechanical properties of the covalently functionalized chain to that of unmodified DNA and to DNA bound to a previously uncharacterized groove-binder, SYBR-gold. Modified DNA species were obtained by covalently linking azide-functionalized organic fluorophores onto the backbone of DNA chains via the alkyne moieties of modified bases that were incorporated during PCR. These DNA molecules were then constructed into dumbbells by attaching polystyrene particles to the respective chain ends via biotin or digoxigenin handles that had been pre-attached to the PCR primers which formed the ends of the synthesized molecule. Using the optical tweezers, the DNA was stretched by separating the two optically trapped polystyrene particles. Displacements of the particles were measured in 3D using an interpolation-based normalized cross correlation method and force-extension curves were calculated and fitted to the worm-like chain model to parameterize the mechanical properties of the DNA. Results showed that both the contour and persistence length of the covalently modified dsDNAs were indistinguishable from that of the unmodified dsDNA, whereas SYBR-gold binding perturbed the contour length of the chain in a force-dependent manner. PMID- 26362182 TI - High-density lipoproteins reduce palmitate-induced cardiomyocyte apoptosis in an AMPK-dependent manner. AB - Palmitate has been implicated in the induction of cardiomyocyte apoptosis via reducing the activity of 5' AMP-activated protein kinase (AMPK). We sought to evaluate whether high-density lipoproteins (HDLs), known for their cardioprotective features and their potential to increase AMPK activity, can reduce palmitate-induced cardiomyocyte apoptosis and whether this effect is AMPK dependent. Therefore, cardiomyocytes were isolated from adult Wistar rat hearts via perfusion on a Langendorff-apparatus and cultured in free fatty acid-free BSA control medium or 0.5 mM palmitate medium in the presence or absence of HDL (5 MUg protein/ml) with or without 0.1 MUM of the AMPK-inhibitor compound S for the analysis of Annexin V/propidium, genes involved in apoptosis and fatty acid oxidation, and cardiomyocyte contractility. We found that HDLs decreased palmitate-induced cardiomyocyte apoptosis as indicated by a reduction in Annexin V-positive cardiomyocytes and an increase in Bcl-2 versus Bax ratio. Concomitantly, HDLs increased the palmitate-impaired expression of genes involved in fatty acid oxidation. Furthermore, HDLs improved the palmitate-impaired cardiomyocyte contractility. All effects were mediated in an AMPK-dependent manner, concluding that HDLs reduce palmitate-induced cardiomyocyte apoptosis, resulting in improved cardiomyocyte contractility through a mechanism involving AMPK. PMID- 26362183 TI - Pivotal role of Sirt6 in the crosstalk among ageing, metabolic syndrome and osteoarthritis. AB - Osteoarthritis (OA) is a chronic degenerative joint disorder commonly associated with metabolic syndrome. As ageing and obesity has a great impact on the initiation/severity of OA, herein we sought to investigate the involvement of Sirt6 in the crosstalk between ageing and metabolic syndrome/OA. Sirt6 haploinsufficiency in mice promoted the expression of inflammatory cytokines in the IPFP. Enhanced inflammation of the IPFP in the aged Sirt6 +/- HFD group was paralleled with accelerated OA change, including osteophyte growth and chondrocyte hypertrophy. Conversely, mesenchyme-specific Sirt6-deficient mice revealed both attenuated chondrocyte hypertrophy and proteoglycan synthesis, although chondrocyte senescence was enhanced as shown in the aged WT mice. Thus Sirt6 has key roles in the relationship among ageing, metabolic syndrome, and OA. PMID- 26362184 TI - Maintenance of sweat glands by stem cells located in the acral epithelium. AB - The skin is responsible for a variety of physiological functions and is critical for wound healing and repair. Therefore, the regenerative capacity of the skin is important. However, stem cells responsible for maintaining the acral epithelium had not previously been identified. In this study, we identified the specific stem cells in the acral epithelium that participate in the long-term maintenance of sweat glands, ducts, and interadnexal epidermis and that facilitate the regeneration of these structures following injury. Lgr6-positive cells and Bmi1 positive cells were found to function as long-term multipotent stem cells that maintained the entire eccrine unit and the interadnexal epidermis. However, while Lgr6-positive cells were rapidly cycled and constantly supplied differentiated cells, Bmi1-positive cells were slow to cycle and occasionally entered the cell cycle under physiological conditions. Upon irradiation-induced injury, Bmi1 positive cells rapidly proliferated and regenerated injured epithelial tissue. Therefore, Bmi1-positive stem cells served as reservoir stem cells. Lgr5-positive cells were rapidly cycled and maintained only sweat glands; therefore, we concluded that these cells functioned as lineage-restricted progenitors. Taken together, our data demonstrated the identification of stem cells that maintained the entire acral epithelium and supported the different roles of three cellular classes. PMID- 26362185 TI - Calreticulin discriminates the proximal region at the N-glycosylation site of Glc1Man9GlcNAc2 ligand. AB - Calreticulin (CRT) is well known as a lectin-like chaperone that recognizes Glc1Man9GlcNAc2 (G1M9)-glycoproteins in the endoplasmic reticulum (ER). However, whether CRT can directly interact with the aglycone moiety (protein portion) of the glycoprotein remains controversial. To improve our understanding of CRT interactions, structure-defined G1M9-derivatives with different aglycones (-OH, Gly-NH2, and -Gly-Glu-(t)Bu) were used as CRT ligands, and their interactions with recombinant CRT were analyzed using thermal shift analysis. The results showed that CRT binds strongly to a G1M9-ligand in the order -Gly-Glu-(t)Bu > Gly-NH2 > -OH, which is the same as that of the reglucosylation of Man9GlcNAc2 (M9)-derivatives by the folding sensor enzyme UGGT (UDP-glucose: glycoprotein glucosyltransferase). Our results indicate that, similar to UGGT, CRT discriminates the proximal region at the N-glycosylation site, suggesting a similar mechanism mediating the recognition of aglycone moieties in the ER glycoprotein quality control system. PMID- 26362186 TI - Notoginsenoside R1 stimulates osteogenic function in primary osteoblasts via estrogen receptor signaling. AB - Notoginsenoside R1 (NGR1), a novel phytoestrogen isolated from Panax notoginseng, has been widely used in the treatment of microcirculatory diseases in Asian countries. Here we investigated the effect of NGR1 on osteoblast differentiation and mineralization process. Furthermore, we also evaluated NGR1's estrogenic properties, especially its effects on estrogen receptors (ERs). NGR1 activated the transcriptional activity of phosphorylated estrogen response element (pERE) luciferase (Luc) and induced ERalpha phosphorylation in hBMSC. In addition, ER activation correlated with induction and was associated with osteoblast differentiation biomarkers including alkaline phosphatase activity and transcription of osteoblastic genes, e.g., type I collagen (COL1), osteonectin, osteocalcin (OC), runt related protein 2 (Runx2), and osterix. NGR1 also promoted the mineralization process of osteoblasts. The NGR1-induced effects were confirmed to be mediated by the ER by the observation that pretreatment of the osteoblasts with the ER antagonist, ICI 182,780 fully blocked the effects. Our results showed that NGR1 stimulates osteogenic differentiation of cultured osteoblasts by activating ER signaling and in turn might be a potential therapeutic alternative for the prevention and treatment of osteoporosis. PMID- 26362187 TI - Altering the orientation of a fused protein to the RNA-binding ribosomal protein L7Ae and its derivatives through circular permutation. AB - RNA-protein complexes (RNPs) are useful for constructing functional nano-objects because a variety of functional proteins can be displayed on a designed RNA scaffold. Here, we report circular permutations of an RNA-binding protein L7Ae based on the three-dimensional structure information to alter the orientation of the displayed proteins on the RNA scaffold. An electrophoretic mobility shift assay and atomic force microscopy (AFM) analysis revealed that most of the designed circular permutants formed an RNP nano-object. Moreover, the alteration of the enhanced green fluorescent protein (EGFP) orientation was confirmed with AFM by employing EGFP on the L7Ae permutant on the RNA. The results demonstrate that targeted fine-tuning of the stereo-specific fixation of a protein on a protein-binding RNA is feasible by using the circular permutation technique. PMID- 26362188 TI - Branched-chain amino acids attenuate early kidney injury in diabetic rats. AB - Diabetic nephropathy (DN) is the most severe diabetic microvascular complication. The pathogenesis of diabetic nephropathy is complex, and oxidative stress plays an important role in the development of diabetic nephropathy. Elevated reactive oxygen species (ROS) levels activate various signaling pathways and influence the activities of transforming growth factor-beta (TGF-beta) and matrix metalloproteinase-9 (MMP-9), which contributes to glomerular hypertrophy. Branched-chain amino acids (BCAAs) are widely used in clinical treatment, and BCAAs can reduce the oxidative stress associated with the diabetic pancreas and some liver diseases. Thus, the aim of the present study was to determine whether BCAAs could attenuate oxidative stress in the kidneys of streptozotocin (STZ) induced diabetic rats to prevent early diabetic kidney injury. Male Wistar rats were fed for two weeks with a normal chow diet or a high-fat diet in which 40% of calories were derived from fat. After this two-week period, the mice fed normal chow were injected with vehicle, while the high-fat diet group was injected intraperitoneally (i.p.) with 40 mg/kg STZ. The STZ-treated group was randomly divided into four subgroups that were treated with different doses of BCAAs or vehicle for two months by oral gavage. Plasma glucose, plasma creatinine, urinary protein and JNK, TGF-beta, and MMP-9 mRNA and protein expression levels were measured in the rats. The ROS levels and proteinuria in the STZ-induced diabetic rats were significantly higher than those in the control groups. Moreover, early kidney injury occurred in the STZ-induced diabetic rats. However, BCAAs treatment decreased ROS levels, proteinuria and kidney injury. Moreover, JNK, TGF-beta and MMP-9 mRNA and protein levels were significantly increased in the diabetic rats when compared with the control rats, and BCAAs treatment reversed these changes. Our results suggest that BCAAs counter oxidative stress in the kidneys of diabetic rats and alleviate diabetic kidney injury via the JNK/TGF-beta/MMP-9 pathway. PMID- 26362189 TI - Curcumin promotes browning of white adipose tissue in a norepinephrine-dependent way. AB - Brown adipose tissue converts energy from food into heat via the mitochondrial uncoupling protein UCP1, defending against cold. In some conditions, inducible 'brown-like' adipocytes, also known as beige adipocytes, can develop within white adipose tissue (WAT). These beige adipocytes have characteristics similar to classical brown adipocytes and thus can burn lipids to produce heat. In the current study, we demonstrated that curcumin (50 or 100 mg/kg/day) decreased bodyweight and fat mass without affecting food intake in mice. We further demonstrated that curcumin improves cold tolerance in mice. This effect was possibly mediated by the emergence of beige adipocytes and the increase of thermogenic gene expression and mitochondrial biogenesis in inguinal WAT. In addition, curcumin promotes beta3AR gene expression in inguinal WAT and elevates the levels of plasma norepinephrine, a hormone that can induce WAT browning. Taken together, our data suggest that curcumin can potentially prevent obesity by inducing browning of inguinal WAT via the norepinephrine-beta3AR pathway. PMID- 26362190 TI - [Triage in emergency departments. Comparative evaluation of 4 international triage systems]. AB - BACKGROUND: Facing increasing pressure emergency departments have to replace the previously unstructured approach used to document incoming patients by a standardized quick method, which allows easy documentation of the results. OBJECTIVES: The article describes the initial situation in international comparison and compares the available systems. The aim is to answer the following questions: what aspects should be taken into consideration when choosing a system, and what impact does this have on the selection of a system. MATERIALS AND METHODS: Starting with the reflection of preliminary thoughts from Hamburg in 2000 regarding system decision-making, these considerations will be supplemented by the latest developments. The legal and factual backgrounds are represented in international comparison and from this the consequences for Germany are derived. Included are the most common five-tier systems Australasian Triage Scale, Canadian Triage and Acuity Scale, Emergency Severity Index and the Manchester Triage System. The systems are summarized and their strengths and weaknesses highlighted. RESULTS AND CONCLUSIONS: In the current situation and circumstances in German emergency departments best usability and maximum safety seems to be promised by the Manchester Triage System. Legal and structural requirements are taken into consideration by this system. Of particular advantage of the system is the international and national networking, which enables the integration of international developments and experience. PMID- 26362191 TI - [Acute mesenteric ischemia]. AB - BACKGROUND: Acute vascular occlusion within the mesenteric circulation leads to ischemic damage of the corresponding bowel segment, which starts on the mucosal level and progresses transmurally. OBJECTIVES: Report on pathogenesis, clinical picture and treatment of various forms of intestinal ischemia. MATERIALS AND METHODS: Analysis of the available literature taking into consideration our own experience. RESULTS: Frequently, predisposing diseases and risk factors are present (e.g., cardiac diseases, hypercoagulability, status post cardiac surgery, circulatory failure, or administration of vasoconstrictive drugs). Acute small bowel ischemia-caused by either mesenteric embolism, mesenteric artery thrombosis, nonocclusive mesenteric ischemia (NOMI) or mesenteric venous thrombosis-represents an acute emergency. If this condition is suspected clinically, the diagnosis must be established immediately by computed tomography of the abdomen with intravenous administration of contrast medium in order to prevent irreversible damage to the small bowel. Medical treatment is supportive. If possible, occluded vessels may be re-opened either by radiologic intervention or surgically. Irreversibly damaged bowel segments must be surgically removed. Ischemic colitis has a benign course in most cases if limited to reversible mucosal damage. The diagnosis is based mainly on colonoscopy and computed tomography findings, and treatment is symptom oriented. Rarely, severe manifestations with a worse prognosis due to considerable comorbidities occur. In such cases, surgical removal of the ischemic bowel is frequently required. CONCLUSION: Even today, acute mesenteric ischemia is associated with a poor prognosis. To improve survival and to reduce long-term morbidity, a rapid and systematic diagnostic workup is mandatory. PMID- 26362192 TI - Patterns of carbon storage in relation to shade tolerance in southern South American species. AB - PREMISE OF THE STUDY: Carbon (C) allocation to storage in woody tissues at the expense of growth is thought to promote shade tolerance, yet few studies on the subject examined C storage during maximum growth and considered stand influences. I asked how C storage in different plant tissues relates to shade tolerance in temperate forests with contrasting climates and physiognomies, and whether relationships vary during the growing season. METHODS: In the late spring and late summer, I harvested seedlings of eight species with contrasting light requirements from the understory of a cold rainforest and a Mediterranean forest in Chile. Nonstructural carbohydrate (NSC) concentrations and pools (i.e., biomass x NSC concentration) were determined in leaves, aboveground wood, and roots. The effects of shade tolerance and sampling date on the NSCs were analyzed for each forest and tissue with linear mixed-effects models. KEY RESULTS: In both forests, concentrations of NSC and soluble sugars in woody tissues, as well as fractions of NSC in these tissues, were lower in shade tolerant than in shade intolerant species. For root NSC concentrations, these trends depended on the sampling date: in the late spring the concentrations were similar in shade tolerant and intolerant species, while in the late summer they were lower in shade tolerant species. CONCLUSIONS: Shade tolerance is not linked to C storage in the two studied forests, suggesting that allocation to growth or defenses could be more advantageous for low light persistence. Alternatively, high levels of C storage could be also selected in shade intolerant species to face herbivory or drought. PMID- 26362193 TI - Effects of range-wide variation in climate and isolation on floral traits and reproductive output of Clarkia pulchella. AB - PREMISE OF THE STUDY: Plant mating systems and geographic range limits are conceptually linked by shared underlying drivers, including landscape-level heterogeneity in climate and in species' abundance. Studies of how geography and climate interact to affect plant traits that influence mating system and population dynamics can lend insight to ecological and evolutionary processes shaping ranges. Here, we examined how spatiotemporal variation in climate affects reproductive output of a mixed-mating annual, Clarkia pulchella. We also tested the effects of population isolation and climate on mating-system-related floral traits across the range. METHODS: We measured reproductive output and floral traits on herbarium specimens collected across the range of C. pulchella. We extracted climate data associated with specimens and derived a population isolation metric from a species distribution model. We then examined how predictors of reproductive output and floral traits vary among populations of increasing distance from the range center. Finally, we tested whether reproductive output and floral traits vary with increasing distance from the center of the range. KEY RESULTS: Reproductive output decreased as summer precipitation decreased, and low precipitation may contribute to limiting the southern and western range edges of C. pulchella. High spring and summer temperatures are correlated with low herkogamy, but these climatic factors show contrasting spatial patterns in different quadrants of the range. CONCLUSIONS: Limiting factors differ among different parts of the range. Due to the partial decoupling of geography and environment, examining relationships between climate, reproductive output, and mating-system-related floral traits reveals spatial patterns that might be missed when focusing solely on geographic position. PMID- 26362194 TI - Novel BRAF and KRAS Mutations in Papillary Thyroid Carcinoma Arising in Struma Ovarii. AB - Papillary carcinomas of thyroid type rarely arise within struma ovarii. There are limited data on the immunohistochemical and molecular features of these tumors. Three cases of papillary carcinoma arising in struma ovarii (PCSO) were identified. The clinicopathological features were reviewed and immunohistochemical staining for HBME-1, cytokeratin (CK) 19, and CD56 was performed. Tumor DNA was sequenced for somatic mutations using a panel of 26 oncogenes, with a particular focus on BRAF and KRAS mutations. The patients were aged 22, 48, and 55 years. All cases were FIGO stage IA. Two tumors were of classical histological type, and one was a follicular variant papillary carcinoma. All tumors expressed HBME-1 and two were positive for CK19. CD56 was negative in all three cases. One tumor demonstrated a BRAF G469A mutation in exon 11, and in a second case, a KRAS Q61K double base mutation in exon 3 was detected. These mutations have not been described previously in PCSO. No mutations were detected in the benign follicular components of the tumors adjacent to the malignant papillary tissue. None of the patients had tumor recurrence on clinical follow-up (range 11 months to 81/2 years). HBME-1, CK19, and CD56 are useful immunohistochemical markers of PCSO. Novel BRAF and KRAS mutations were identified in two of three tumors suggesting that mutations in PCSO may differ from those commonly identified in papillary carcinoma of the eutopic thyroid. The clinical significance of these mutations is uncertain but follow-up data in this small series support the generally good prognosis of PCSO. PMID- 26362195 TI - Does antihypertensive treatment with renin-angiotensin system inhibitors prevent the development of diabetic kidney disease? AB - BACKGROUND: Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease worldwide. Renin-angiotensin system (RAS) inhibitors are the first-line treatment for diabetic patients with hypertension. However, whether RAS inhibitors prevent the development of DKD remains controversial. We conducted a retrospective cohort study quantifying the preventive effect of antihypertensive treatment with RAS inhibitors on DKD, using data from specific health check-ups and health insurance claims. METHODS: The study subjects were 418 patients with diabetes and hypertension, drawn from health insurance societies located in Fukuoka and Shizuoka prefectures in Japan. The subjects were divided into three groups, according to the type of antihypertensive treatment they received. They were then compared in terms of the development of DKD, using the diagnostic codes from ICD-10. RESULTS: Thirty subjects (6.2%) developed DKD during the study period between April 2011 and September 2013. RAS inhibitor treated group showed a significantly lower risk of DKD [adjusted odds ratio (AOR) = 0.35; 95% confidential interval (CI): 0.16-0.76] compared with the no treatment group. CONCLUSION: We conclude that antihypertensive treatment with RAS inhibitors is potentially useful for preventing the development of DKD. PMID- 26362196 TI - Long non-coding RNA Loc554202 induces apoptosis in colorectal cancer cells via the caspase cleavage cascades. AB - BACKGROUND: Aberrant expression of long noncoding RNAs (lncRNAs) has frequently been reported in cancer studies, including those of colorectal cancer (CRC). Increasing evidence suggests that lncRNAs are significantly correlated with the pathogenesis, development and metastasis of cancer. Loc554202 is a 2166-bp transcript on human chromosome 9p21.3, the expression of which is dysregulated in breast and lung cancer cells. However, its role in CRC remains under investigation. METHODS: Quantitative real-time polymerase chain reaction (qRT PCR) was carried out to assess the relative expression of Loc554202 in CRC cell lines and tissues. Gain and/or loss of function approaches were used to investigate the potential functional roles in cell proliferation and apoptosis in vitro and in vivo. qRT-PCR, western-blotting and immunohistochemistry were used to evaluate the mRNA and protein expression of apoptosis-related factors. RESULTS: Loc554202 was significantly downregulated in cancerous tissues and CRC cell lines compared with adjacent normal tissue and a normal human intestinal epithelial cell line. Low Loc554202 expression was closely associated with advanced pathologic stage and a larger tumor size. The overexpression of Loc554202 decreased the cell proliferation and induced apoptosis in vitro and hindered tumorigenesis in vivo. Loc554202 regulated cell apoptosis partly through the activation of specific caspase cleavage cascades. CONCLUSION: Our results suggest that Loc554202 may play an important role in the progression of CRC and could be a candidate prognostic biomarker or a target for new cancer therapies. PMID- 26362197 TI - Optimizing the clinical utility of PCA3 to diagnose prostate cancer in initial prostate biopsy. AB - BACKGROUND: PCA3 has been included in a nomogram outperforming previous clinical models for the prediction of any prostate cancer (PCa) and high grade PCa (HGPCa) at the initial prostate biopsy (IBx). Our objective is to validate such IBx specific PCA3-based nomogram. We also aim to optimize the use of this nomogram in clinical practice through the definition of risk groups. METHODS: Independent external validation. Clinical and biopsy data from a contemporary cohort of 401 men with the same inclusion criteria to those used to build up the reference's nomogram in IBx. The predictive value of the nomogram was assessed by means of calibration curves and discrimination ability through the area under the curve (AUC). Clinical utility of the nomogram was analyzed by choosing thresholds points that minimize the overlapping between probability density functions (PDF) in PCa and no PCa and HGPCa and no HGPCa groups, and net benefit was assessed by decision curves. RESULTS: We detect 28% of PCa and 11 % of HGPCa in IBx, contrasting to the 46 and 20% at the reference series. Due to this, there is an overestimation of the nomogram probabilities shown in the calibration curve for PCa. The AUC values are 0.736 for PCa (C.I.95%:0.68-0.79) and 0.786 for HGPCa (C.I.95%:0.71-0.87) showing an adequate discrimination ability. PDF show differences in the distributions of nomogram probabilities in PCa and not PCa patient groups. A minimization of the overlapping between these curves confirms the threshold probability of harboring PCa >30 % proposed by Hansen is useful to indicate a IBx, but a cut-off > 40% could be better in series of opportunistic screening like ours. Similar results appear in HGPCa analysis. The decision curve also shows a net benefit of 6.31% for the threshold probability of 40%. CONCLUSIONS: PCA3 is an useful tool to select patients for IBx. Patients with a calculated probability of having PCa over 40% should be counseled to undergo an IBx if opportunistic screening is required. PMID- 26362198 TI - Downregulation of PHEX in multibacillary leprosy patients: observational cross sectional study. AB - BACKGROUND: Peripheral nerve injury and bone lesions, well known leprosy complications, lead to deformities and incapacities. The phosphate-regulating gene with homologies to endopeptidase on the X chromosome (PHEX) encodes a homonymous protein (PHEX) implicated in bone metabolism. PHEX/PHEX alterations may result in bone and cartilage lesions. PHEX expression is downregulated by intracellular Mycobacterium leprae (M. leprae) in cultures of human Schwann cells and osteoblasts. M. leprae in vivo effect on PHEX/PHEX is not known. METHODS: Cross-sectional observational study of 36 leprosy patients (22 lepromatous and 14 borderline-tuberculoid) and 20 healthy volunteers (HV). The following tests were performed: PHEX flow cytometric analysis on blood mononuclear cells, cytokine production in culture supernatant, 25-hydroxyvitamin D (OHvitD) serum levels and (99m)Tc-MDP three-phase bone scintigraphy, radiography of upper and lower extremities and blood and urine biochemistry. RESULTS: Significantly lower PHEX expression levels were observed in lepromatous patients than in the other groups (chi(2) = 16.554, p < 0.001 for lymphocytes and chi(2) = 13.933, p = 0.001 for monocytes). Low levels of 25-(OHvitD) were observed in HV (median = 23.0 ng/mL) and BT patients (median = 27.5 ng/mL) and normal serum levels were found in LL patients (median = 38.6 ng/mL). Inflammatory cytokines, such as TNF, a PHEX transcription repressor, were lower after stimulation with M. leprae in peripheral blood mononuclear cells from lepromatous in comparison to BT patients and HV (chi(2) = 10.820, p < 0.001). CONCLUSION: Downregulation of PHEX may constitute an important early component of bone loss and joint damage in leprosy. The present results suggest a direct effect produced by M. leprae on the osteoarticular system that may use this mechanism. PMID- 26362199 TI - Progress testing in the medical curriculum: students' approaches to learning and perceived stress. AB - BACKGROUND: Progress Tests (PTs) draw on a common question bank to assess all students in a programme against graduate outcomes. Theoretically PTs drive deep approaches to learning and reduce assessment-related stress. In 2013, PTs were introduced to two year groups of medical students (Years 2 and 4), whereas students in Years 3 and 5 were taking traditional high-stakes assessments. Staged introduction of PTs into our medical curriculum provided a time-limited opportunity for a comparative study. The main purpose of the current study was to compare the impact of PTs on undergraduate medical students' approaches to learning and perceived stress with that of traditional high-stakes assessments. We also aimed to investigate the associations between approaches to learning, stress and PT scores. METHODS: Undergraduate medical students (N = 333 and N = 298 at Time 1 and Time 2 respectively) answered the Revised Study Process Questionnaire (R-SPQ-2F) and the Perceived Stress Scale (PSS) at two time points to evaluate change over time. The R-SPQ-2F generated a surface approach and a deep approach score; the PSS generated an overall perceived stress score. RESULTS: We found no significant differences between the two groups in approaches to learning at either time point, and no significant changes in approaches to learning over time in either cohort. Levels of stress increased significantly at the end of the year (Time 2) for students in the traditional assessment cohort, but not in the PT cohort. In the PT cohort, surface approach to learning, but not stress, was a significant negative predictor of students' PT scores. CONCLUSIONS: While confirming an association between surface approaches to learning and lower PT scores, we failed to demonstrate an effect of PTs on approaches to learning. However, a reduction in assessment-associated stress is an important finding. PMID- 26362200 TI - Re: Long-term recurrence and chronic pain after repair for small umbilical or epigastric hernias: a regional cohort study. PMID- 26362201 TI - Can sepsis predict deep venous thrombosis in colorectal surgery? AB - BACKGROUND: Little data exist regarding the impact of sepsis on deep venous thrombosis (DVT) in colorectal surgery patients. We sought to elucidate this relationship. METHODS: Current Procedural Terminology codes were used to identify patients who underwent colorectal surgery as reported to the National Surgical Quality Improvement Program in 2010. The relationship between DVT and sepsis was then explored in a matched population. RESULTS: Of the 26,554 patients who underwent colorectal surgery, 462 (1.7%) developed a DVT. The largest dependent correlations with DVT were malnutrition (33% vs 57%), emergency operation (15% vs 31%), open operation (58% vs 78%), and prolonged ventilator requirement (5% vs 24%; all P < .001). After propensity score matching, urosepsis (.5% vs 1.9%), organ/space sepsis (1.1% vs 4.8%), pneumosepsis (.5% vs 5.8%), and overall perioperative sepsis (18% vs 39%; all P <= .04) were associated with DVT. The strongest independent predictor of DVT was pneumosepsis (odds ratio 15.9, 95% confidence interval 3.7 to 67.2, P < .001). CONCLUSION: Perioperative sepsis is a significant risk factor for postoperative DVT in the colorectal surgery population. PMID- 26362202 TI - Defining surgical outcomes and quality of life in massive ventral hernia repair: an international multicenter prospective study. AB - BACKGROUND: Our goal was to set criteria for massive ventral hernia and to compare surgical outcomes and quality of life after ventral hernia repair (VHR). METHODS: The International Hernia Mesh Registry was queried for patients undergoing VHR from 2007 to 2013. Defect was categorized as massive if the width or length was greater than 15 cm or area greater than 150 cm(2). Massive VHR was compared to regular VHR. RESULTS: A total of 878 patients underwent VHR: 436 open, 442 laparoscopic with 13 deaths (1.5%) and 45 hernia recurrences (5.1%). Of those, 158 patients (18%) met criteria for massive VHR. Massive VHR patients had longer length of stay (LOS) and operative time and more hematomas, wound infections, wound complications, and pneumonias (P < .05). On multivariate analysis, LOS was longer, and early postoperative pain and activity limitation were greater in massive VHRs (P < .01). Massive VHR in the laparoscopic approach resulted in greater long-term mesh sensation (P < .01). CONCLUSIONS: VHR in massive hernias have increased rates of complications and longer LOS. PMID- 26362203 TI - Diagnostic value of maspin in distinguishing adenocarcinoma from benign biliary epithelium on endoscopic bile duct biopsy. AB - Histopathologic distinction between benign and malignant epithelia on endoscopic bile duct biopsy can be extremely challenging due to small sample size, crush artifact, and a propensity for marked inflammatory and reactive changes after stent placement. Our previous studies have shown that the insulin-like growth factor II mRNA-binding protein 3, S100P, and the von Hippel-Lindau gene product (pVHL) can help the distinction. This study analyzed 134 endoscopic bile duct biopsy specimens (adenocarcinoma 45, atypical 31, and benign 58) by immunohistochemistry for the expression of maspin, a serine protease inhibitor. The results demonstrated that (1) maspin expression was more frequently detected in malignant than in benign biopsies; (2) malignant biopsies frequently showed diffuse, strong/intermediate, and combined nuclear/cytoplasmic staining patterns for maspin, which were much less commonly seen in benign biopsies; (3) the malignant staining patterns for maspin observed in atypical biopsies were consistent with follow-up data showing that 67% of these patients were subsequently diagnosed with adenocarcinoma; (4) a maspin+/S100P+/pVHL- staining profile was seen in 75% of malignant biopsies but in none of the benign cases. These observations demonstrate that maspin is a useful addition to the diagnostic immunohistochemical panel (S100P, pVHL, and insulin-like growth factor II mRNA binding protein 3) to help distinguish malignant from benign epithelia on challenging bile duct biopsies. PMID- 26362204 TI - Increased oxidative stress contributes to cardiomyocyte dysfunction and death in patients with Fabry disease cardiomyopathy. AB - Cardiac dysfunction of Fabry disease (FD) has been associated with myofilament damage and cell death as result of alpha-galactosidase A deficiency and globotriaosylceramide accumulation. We sought to evaluate the role of oxidative stress in FD cardiomyocyte dysfunction. Myocardial tissue from 18 patients with FD was investigated for the expression of inducible nitric oxide synthase (iNOS) and nitrotyrosine by immunohistochemistry. Western blot analysis for nitrotyrosine was also performed. Oxidative damage to DNA was investigated by immunostaining for 8-hydroxydeoxyguanosine (8-OHdG), whereas apoptosis was evaluated by in situ ligation with hairpin probes. iNOS and nitrotyrosine expression was increased in FD hearts compared with hypertrophic cardiomyopathy and normal controls. Remarkably, immunostaining was homogeneously expressed in FD male cardiomyocytes, whereas it was only detected in the affected cardiomyocytes of FD females. Western blot analysis confirmed an increase in FD cardiomyocyte protein nitration compared with controls. 8-OHdG was expressed in 25% of cardiomyocyte nuclei from FD patients, whereas it was absent in controls. The intensity of immunostaining for iNOS/nitrotyrosine correlated with 8-OHdG expression in cardiomyocyte nuclei. Apoptosis of FD cardiomyocytes was 187-fold higher than in controls, and apoptotic nuclei were positive for 8-OHdG. Cardiac dysfunction of FD reflects increased myocardial nitric oxide production with oxidative damage of cardiomyocyte myofilaments and DNA, causing cell dysfunction and death. PMID- 26362205 TI - Artificial sweetener neohesperidin dihydrochalcone showed antioxidative, anti inflammatory and anti-apoptosis effects against paraquat-induced liver injury in mice. AB - The present study evaluated the protective effect of artificial sweetener neohesperidin dihydrochalcone (NHDC) against paraquat (PQ)-induced acute liver injury in mice. A single dose of PQ (75mg/kg body weight, i.p.) induced acute liver toxicity with the evidences of increased liver damage biomarkers, aspartate transaminase (AST) and alanine transaminase (ALT) activities in serum. Consistently, PQ decreased the antioxidant capacity by reducing glutathione peroxidase (GP-X), glutathione-S-transferase (GST) and catalase (CAT) activities, glutathione (GSH) level and total antioxidant capacity (T-AOC), as well as increasing reactive oxygen species (ROS) and thiobarbituric acid reactive substances (TBARS) levels. Histopathological examination revealed that PQ induced numerous changes in the liver tissues. Immunochemical staining assay indicated the upregulation of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expressions. However, NHDC ameliorates PQ-induced hepatic toxicity in mice by reversing these parameters. Additionally, NHDC significantly inhibited PQ induced nuclear factor-kappa B (NF-kappaB) expression and mitochondrial-driven apoptotic signaling. TUNEL assay confirmed that PQ-induced apoptosis was relieved by NHDC. In conclusion, these findings suggested that NHDC showed potent antioxidant, anti-inflammatory and anti-apoptotic effects against PQ-induced acute liver damage. PMID- 26362206 TI - Recent progress in revealing the biological and medical significance of the non neuronal cholinergic system. AB - This special issue of International Immunopharmacology is the proceedings of the Fourth International Symposium on Non-neuronal Acetylcholine that was held on August 28-30, 2014 at the Justus Liebig University of Giessen in Germany. It contains original contributions of meeting participants covering the significant progress in understanding of the biological and medical significance of the non neuronal cholinergic system extending from exciting insights into molecular mechanisms regulating this system via miRNAs over the discovery of novel cholinergic cellular signaling circuitries to clinical implications in cancer, wound healing, immunity and inflammation, cardiovascular, respiratory and other diseases. PMID- 26362207 TI - Inhibition of airway inflammation and remodeling by sitagliptin in murine chronic asthma. AB - In this study the role of sitagliptin, dipeptidyl peptidase inhibitor, DPP-4, and dexamethasone in ameliorating inflammation and remodeling of chronic asthma in a mouse model were investigated. Mice sensitized to ovalbumin were chronically challenged with aerosolized antigen for 3days a week continued for 8weeks. During this period animals were treated with sitagliptin or dexamethasone daily. Assessment of inflammatory cell, oxidative markers, total nitrate/nitrite (NOx), interleukin (IL)-13, transforming growth factor-beta1 (TGF-beta1) in bronchoalveolar lavage (BAL) and/or lung tissue were done. Also histopathological and immuno-histochemical analysis for lung was carried out. Compared with vehicle alone, treatment with sitagliptin or dexamethasone significantly reduced accumulation of eosinophils and chronic inflammatory cells, subepithelial collagenization, and thickening of the airway epithelium. Also both drug reduced goblet cell hyperplasia, oxidative stress, TGF-beta1, IL-13 and epithelial cytoplasmic immunoreactivity for nuclear factor kappa-B (NFkappa-B). These data indicate that sitagliptin like dexamethasone may play a beneficial role reducing airway inflammation and remodeling in chronic murine model of asthma. PMID- 26362208 TI - Protective and immunogenic effects of Escherichia coli-expressed infectious pancreatic necrosis virus (IPNV) VP2-VP3 fusion protein in rainbow trout. AB - Infectious Pancreatic Necrosis Virus (IPNV) is a member of the family Birnaviridae which causes significant losses in the aquaculture industry. To develop a recombinant vaccine for IPNV, a cDNA construct of IPNV VP2-VP3 fusion gene was prepared and cloned into an Escherichia coli (E. coli) expression vector (pET-26b) to obtain recombinant protein products. A study was conducted to determine the antibody responses and protective capacity of this recombinant vaccine expressing VP2-VP3 fusion protein. Subsequently, juvenile rainbow trout were inoculated by injecting purified recombinant IPNV VP2-VP3 proteins, followed by challenge with virulent IPNV in rainbow trout. Our results demonstrate that recombinant E. coli derived VP2-VP3 fusion protein induced a strong and significantly (P < 0.05) higher IgM antibody response in serum samples compared to control groups. Following intraperitoneal challenge, the relative percent survival (RPS) rate of survivors was 83% for the vaccinated group. Statistical analysis of IgM levels indicated that immunogenicity of recombinant VP2-VP3 protein, combined with adjuvant, was much higher than any other groups of rainbow trout challenged with virulent IPNV. This result was confirmed by measuring the viral loads of IPNV in immunized rainbow trout which was drastically reduced, as analyzed by real-time RT-PCR. In summary, we demonstrate that E. coli-expressed IPNV VP2-VP3 injectable vaccine is highly immunogenic and protective against IPNV infection. PMID- 26362209 TI - The first echinoderm poly-U-binding factor 60 kDa (PUF60) from sea cucumber (Stichopus monotuberculatus): Molecular characterization, inducible expression and involvement of apoptosis. AB - Poly-U-binding factor 60 kDa (PUF60), also known as Ro RNA binding protein (RoBPI) and FBP interacting repressor (FIR), is a multifunctional protein that is involved in a variety of nuclear processes including pre-mRNA splicing, apoptosis and transcription regulation. In this study, the first echinoderm PUF60 named StmPUF60 was identified from sea cucumber (Stichopus monotuberculatus). The StmPUF60 cDNA is 4503 bp in length, containing a 5'-untranslated region (UTR) of 34 bp, a 3'-UTR of 2963 bp and an open reading frame (ORF) of 1506 bp that encoding a protein of 501 amino acids with a deduced molecular weight of 54.15 kDa and a predicted isoelectric point of 5.15. The putative StmPUF60 protein possesses all the main characteristics of known PUF60 proteins, including two RNA recognition motifs (RRM1 and RRM2), a C-terminal PUMP domain and two conserved nucleic acid-binding ribonucleoprotein sequences (RNP1 and RNP2). For the gene structure, StmPUF60 contains nine exons separated by eight introns. In addition, the highest level of StmPUF60 mRNA expression was noticed in the gonad, followed by coelomocytes, intestine, respiratory tree and body wall. In in vivo experiments, the expression of StmPUF60 mRNA in coelomocytes and intestine was significantly up-regulated by lipopolysaccharides (LPS) challenge, suggesting that the sea cucumber PUF60 might play critical roles in the innate immune defense against bacterial infections. Moreover, we further confirmed that overexpressed StmPUF60 could induce apoptosis, and this function of StmPUF60 may be one of the innate immune defense mechanisms for sea cucumber against pathogen infections. PMID- 26362210 TI - Chronic stress effects of high doses of vitamin D3 on Megalobrama amblycephala. AB - Dietary vitamin D3 plays an important role in the growth of aquatic animals, but long-term excessive feeding has potential hazards. In this study, Megalobrama amblycephala specimens were fed different experimental diets with 2000 IU/kg or 200,000 IU/kg of vitamin D3 for 90 days, in order to evaluate chronic stress effects of high doses of vitamin D3 on growth, immunity, and structural damage to enterohepatic tissues. The results showed that high doses of vitamin D3 did not have a significant influence on the growth performance of M. amblycephala (P > 0.05), but it significantly reduced the survival rate after infection by Aeromonas hydrophila (P < 0.05). Serum albumin, alkaline phosphatase, and insulin levels, as well as hepatic total antioxidant capacity, were also significantly reduced (P < 0.05). Serum cortisol levels and hepatic heat stress protein 70 expression in M. amblycephala showed that high doses of vitamin D3 significantly inhibit the anti-stress ability of M. amblycephala (P < 0.05). Paraffin tissue sections and electron microscopy showed that high doses of vitamin D3 could cause different degrees of structural damage to enterohepatic tissues of M. amblycephala. Our results indicate that, although M. amblycephala can tolerate high doses of dietary vitamin D3 over a long period, its glycolipid metabolism, immune function, anti-stress function, and resistance to pathogenic infections are adversely affected. PMID- 26362211 TI - BMA agrees to re-enter talks over new consultant contract. PMID- 26362212 TI - A rare occurrence of hepatic portal venous gas in a patient with chemotherapy induced enterocolitis: the rise of benign aetiologies. AB - Hepatic portal venous gas (HPVG) is often viewed as an ominous imaging finding with a poor prognosis and a high mortality rate. We recently encountered a case of HPVG in a patient with advanced metastatic prostate cancer previously treated with chemotherapy and radiotherapy. A laparotomy was performed, which was negative. Although HPVG secondary to chemotherapy is extremely rare, we as clinicians need to consider this aetiology and other benign aetiologies. With the increased rate of benign aetiologies and their successful conservative management, the role of emergency laparotomies needs to be re-considered. PMID- 26362213 TI - David Oliver: What to do about end of life scare stories. PMID- 26362214 TI - New functional and aesthetic composite materials used as an alternative to traditional post materials for the restoration of endodontically treated teeth. AB - OBJECTIVES: To tailor composites of polyethylene-hydroxyapatite to function as a new intracanal post for the restoration of endodontically treated teeth (ETT). METHODS: Silanated hydroxyapatite (HA) and zirconium dioxide (ZrO2) filled low density polyethylene (LDPE) composites were fabricated by a melt extrusion process and characterised using infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and dynamic mechanical analysis (DMA). The flexural strength and modulus were determined in dry state and post ageing in simulated body fluid and fractured surfaces analysed by SEM. The water uptake and radiographic appearance of the experimental composites were also measured and compared with a commercially known endodontic fibre post. Data were submitted to one-way analysis of variance (ANOVA) and post hoc Tukey multiple comparison tests at a level of significance P<0.05. RESULTS: The LDPE/HA composites were structurally flexible and the HA content had a significant effect on the flexural strength and modulus. A univariate analysis of variance showed no significant differences in modulus and strength (P<0.05) post accelerated ageing in simulated body fluid with very low water uptake. The melting point of the LDPE/HA composites ranged between 135 and 136 degrees C, which would facilitate removal in case of retreatment using conventional dental heating devices. The inclusion of HA reduced the damping thereby enhancing dimensional stability, whilst the addition of zirconia yielded a semi-translucent material that was sufficiently radiopaque, comparable to commercial posts, thus yielding aesthetic materials. CONCLUSIONS: Innovative materials for restoration of ETT were developed; offering considerable benefits over the currently available material in terms of biomechanical and thermal properties. CLINICAL SIGNIFICANCE: This study provided a new option for the development of a new intracanal post made up of functional and aesthetic composites. PMID- 26362215 TI - DNA-binding properties of a cGMP-binding CRP homologue that controls development of metabolically dormant cysts of Rhodospirillum centenum. AB - Rhodospirillum centenum utilizes 3',5'-cyclic guanosine monophosphate (cGMP) as a messenger to regulate development of desiccation-resistant cysts. In this study, we demonstrated that gcyA, gcyB and gcyC, coding for putative subunits of a guanylyl cyclase, increase expression from 8- to 500-fold when cells transition from vegetative to cyst phases of growth. This induction did not occur in a strain that is defective in cGMP synthesis or in a strain that contains a deletion of cgrA that codes for a cGMP-binding homologue of Escherichia coli catabolite repressor protein (CRP). We also demonstrated that cgrA auto-induces its own expression in the presence of cGMP, indicating that a feed-forward loop is used to ramp up cGMP production as cells undergo encystment. Inspection of an intragenic region upstream of gcyB revealed a sequence that is identical to the CRP consensus sequence from E. coli. DNase I and fluorescence anisotropy analyses demonstrated that CgrA bound to this target sequence at a protein : cGMP ratio of 1 : 2 with Kd ~61 nM. This was in contrast to CgrA in the presence of cAMP, which exhibited Kd ~1795 nM. CgrA thus constitutes a novel variant of CRP that utilizes cGMP to regulate production of cGMP synthase for the control of cyst development. PMID- 26362216 TI - Red blood cells open promising avenues for longitudinal studies of ageing in laboratory, non-model and wild animals. AB - Ageing is characterized by a progressive deterioration of multiple physiological and molecular pathways, which impair organismal performance and increase risks of death with advancing age. Hence, ageing studies must identify physiological and molecular pathways that show signs of age-related deterioration, and test their association with the risk of death and longevity. This approach necessitates longitudinal sampling of the same individuals, and therefore requires a minimally invasive sampling technique that provides access to the larger spectrum of physiological and molecular pathways that are putatively associated with ageing. The present paper underlines the interest in using red blood cells (RBCs) as a promising target for longitudinal studies of ageing in vertebrates. RBCs provide valuable information on the following six pathways: cell maintenance and turnover (RBC number, size, and heterogeneity), glucose homeostasis (RBC glycated haemoglobin), oxidative stress parameters, membrane composition and integrity, mitochondrial functioning, and telomere dynamics. The last two pathways are specific to RBCs of non-mammalian species, which possess a nucleus and functional mitochondria. We present the current knowledge about RBCs and age-dependent changes in these pathways in non-model and wild species that are especially suitable to address questions related to ageing using longitudinal studies. We discuss how the different pathways relate with survival and lifespan and give information on their genetic and environmental determinants to appraise their evolutionary potential. PMID- 26362217 TI - What can long-lived mutants tell us about mechanisms causing aging and lifespan variation in natural environments? AB - Long-lived mutants of model organisms have brought remarkable progress in our understanding of aging mechanisms. However, long-lived mutants are usually maintained in optimal standardized laboratory environments (SLEs), and it is not obvious to what extent insights from long-lived mutants in SLEs can be generalized to more natural environments. To address this question, we reviewed experiments that compared the fitness and lifespan advantage of long-lived mutants relative to wild type controls in SLEs and more challenging environments in various model organisms such as yeast Saccharomyces cerevisiae, the nematode worm Caenorhabditis elegans, the fruitfly Drosophila melanogaster and the mouse Mus musculus. In competition experiments over multiple generations, the long lived mutants had a lower fitness relative to wild type controls, and this disadvantage was the clearest when the environment included natural challenges such as limited food (N=6 studies). It is well known that most long-lived mutants have impaired reproduction, which provides one reason for the fitness disadvantage. However, based on 12 experiments, we found that the lifespan advantage of long-lived mutants is diminished in more challenging environments, often to the extent that the wild type controls outlive the long-lived mutants. Thus, it appears that information on aging mechanisms obtained from long-lived mutants in SLEs may be specific to such environments, because those same mechanisms do not extend lifespan in more natural environments. This suggests that different mechanisms cause variation in aging and lifespan in SLEs compared to natural populations. PMID- 26362218 TI - Age gene expression and coexpression progressive signatures in peripheral blood leukocytes. AB - Both cellular senescence and organismic aging are known to be dynamic processes that start early in life and progress constantly during the whole life of the individual. In this work, with the objective of identifying signatures of age related progressive change at the transcriptomic level, we have performed a whole genome gene expression analysis of peripheral blood leukocytes in a group of healthy individuals with ages ranging from 14 to 93 years. A set of genes with progressively changing gene expression (either increase or decrease with age) has been identified and contextualized in a coexpression network. A modularity analysis has been performed on this network and biological-term and pathway enrichment analyses have been used for biological interpretation of each module. In summary, the results of the present work reveal the existence of a transcriptomic component that shows progressive expression changes associated to age in peripheral blood leukocytes, highlighting both the dynamic nature of the process and the need to complement young vs. elder studies with longitudinal studies that include middle aged individuals. From the transcriptional point of view, immunosenescence seems to be occurring from a relatively early age, at least from the late 20s/early 30s, and the 49-56 year old age-range appears to be critical. In general, the genes that, according to our results, show progressive expression changes with aging are involved in pathogenic/cellular processes that have classically been linked to aging in humans: cancer, immune processes and cellular growth vs. maintenance. PMID- 26362219 TI - The heuristic value of redundancy models of aging. AB - Molecular studies of aging aim to unravel the cause(s) of aging bottom-up, but linking these mechanisms to organismal level processes remains a challenge. We propose that complementary top-down data-directed modelling of organismal level empirical findings may contribute to developing these links. To this end, we explore the heuristic value of redundancy models of aging to develop a deeper insight into the mechanisms causing variation in senescence and lifespan. We start by showing (i) how different redundancy model parameters affect projected aging and mortality, and (ii) how variation in redundancy model parameters relates to variation in parameters of the Gompertz equation. Lifestyle changes or medical interventions during life can modify mortality rate, and we investigate (iii) how interventions that change specific redundancy parameters within the model affect subsequent mortality and actuarial senescence. Lastly, as an example of data-directed modelling and the insights that can be gained from this, (iv) we fit a redundancy model to mortality patterns observed by Mair et al. (2003; Science 301: 1731-1733) in Drosophila that were subjected to dietary restriction and temperature manipulations. Mair et al. found that dietary restriction instantaneously reduced mortality rate without affecting aging, while temperature manipulations had more transient effects on mortality rate and did affect aging. We show that after adjusting model parameters the redundancy model describes both effects well, and a comparison of the parameter values yields a deeper insight in the mechanisms causing these contrasting effects. We see replacement of the redundancy model parameters by more detailed sub-models of these parameters as a next step in linking demographic patterns to underlying molecular mechanisms. PMID- 26362220 TI - Tissue loss with subcutaneous immunotherapy--Nicolau syndrome. PMID- 26362221 TI - [Practical risk analysis]. AB - Risk analysis is typically considered from two complementary points of view: predictive analysis performed prior, and retrospective analysis, which follows the internal reporting of adverse situations or malfunctions, both on the organizational and material or human aspects. The purpose of these additional analyzes is to ensure that planned or implemented measures allow to keep risks to a level deemed tolerable or acceptable at a given time and in a given situation. Where a risk is deemed unacceptable, risk reduction measures should be considered (prevention, limiting the consequences and protection). PMID- 26362222 TI - Letter to the Editor of the Journal of Microbiological Methods. PMID- 26362223 TI - Reply of the authors. PMID- 26362224 TI - Evaluation of baicalein, chitosan and usnic acid effect on Candida parapsilosis and Candida krusei biofilm using a Cellavista device. AB - Biofilms are often the cause of chronic human infections and contaminate industrial or medical equipment. The traditional approach has been to use increasing concentrations of antibiotics, but microorganisms rapidly develop multiresistance to them. Therefore, we investigated the use of natural substances as an alternative solution. The quantification of the biofilms based on the colonized areas was measured using a Cellavista automatic microscope equipped with image analysis software. Using the Cellavista device brings new possibilities for qualification and quantification of sessile cells. In our study, this feature was documented by exploring the antifungal/anti-biofilm activity of amphotericin B, baicalein, chitosan and usnic acid against yeast biofilm formation. The influence of these substances on the formation and eradication of opportunistic pathogenic yeasts Candida parapsilosis and Candida krusei biofilms was studied in 96-well polystyrene microtiter plates. While amphotericin B was not very efficient, the use of baicalein and chitosan, even in minimum inhibitory concentrations, was found to rapidly decrease the colonized areas in the wells. The usnic acid did not display any significant antibiofilm properties even at concentration 300MUgml(-1). Our results propose that Cellavista is a promising tool for the study of yeast biofilm formation and the effects of antimicrobial agents. PMID- 26362225 TI - Supervised recursive segmentation of volumetric CT images for 3D reconstruction of lung and vessel tree. AB - Three dimensional reconstruction of lung and vessel tree has great significance to 3D observation and quantitative analysis for lung diseases. This paper presents non-sheltered 3D models of lung and vessel tree based on a supervised semi-3D lung tissues segmentation method. A recursive strategy based on geometric active contour is proposed instead of the "coarse-to-fine" framework in existing literature to extract lung tissues from the volumetric CT slices. In this model, the segmentation of the current slice is supervised by the result of the previous one slice due to the slight changes between adjacent slice of lung tissues. Through this mechanism, lung tissues in all the slices are segmented fast and accurately. The serious problems of left and right lungs fusion, caused by partial volume effects, and segmentation of pleural nodules can be settled meanwhile during the semi-3D process. The proposed scheme is evaluated by fifteen scans, from eight healthy participants and seven participants suffering from early-stage lung tumors. The results validate the good performance of the proposed method compared with the "coarse-to-fine" framework. The segmented datasets are utilized to reconstruct the non-sheltered 3D models of lung and vessel tree. PMID- 26362227 TI - The impact of depression and diabetes mellitus on older workers' functioning. AB - OBJECTIVE: Using the International Classification of Functioning, Disability and Health as a framework, this study investigates the impact of depression and diabetes mellitus on older workers' functioning (problems with concentration, physical functioning, need for recovery and work and social participation restrictions). The study focuses on how these chronic conditions, in their interaction with the work context, affect older workers' functioning, which may be an important precursor of early retirement. METHODS: Older workers (>= 45years) with depression (n=127) or diabetes mellitus (n=107) enrolled in the prospective Maastricht Cohort Study (MCS) were followed between October 2008 and October 2012. Linear, logistic and Cox regression analyses were performed to investigate the effect of these health conditions on workers' functioning compared to a reference group of older workers without a chronic condition (n=1612). The interaction with participants' working conditions (psychological job demands, decision latitude and strenuous work) was also analysed. RESULTS: Compared to the reference group, depression and diabetes mellitus were (over time) positively related with need for recovery caseness and restrictions in social participation but not with restrictions in work participation. Depression was positively related with concentration problems and need for recovery, whereas diabetes mellitus was negatively related with physical functioning. Finally, the relationship between functioning and depression and diabetes mellitus depends on working conditions. CONCLUSION: Older workers with depression or diabetes mellitus are vulnerable to losses in specific domains of functioning. The impact on functioning varies across working conditions, providing insight for disease tailored preventive measures. PMID- 26362226 TI - Tibial bone responses to 6-month calcium and vitamin D supplementation in young male jockeys: A randomised controlled trial. AB - Young male jockeys compromise bone health by engaging in caloric restriction and high volumes of physical activity during periods of musculoskeletal growth and development. The aim of this randomised, double-blinded, placebo-controlled trial was to establish whether calcium and vitamin D supplementation would improve bone properties of young male jockeys. We conducted a 6-month trial with two groups of weight-, height- and age-matched apprentice male jockeys (age=20.2 +/- 3.2 yrs). Participants were supplemented with 800 mg of calcium and 400 IU of vitamin D (S, n=8) or a placebo (cellulose) (P, n=9) daily for 6-months. Baseline calcium intake was (669.7 +/- 274.3 (S) vs 790.4 +/- 423.9 (P) and vitamin D 64.6 +/- 19.5 (S) vs 81.2 +/- 24.4 (P) with no statistical differences. Peripheral quantitative computed tomography (pQCT) measured ultra-distal (4%) and proximal (66%) tibial bone properties at baseline and 6 months. Blood-borne markers of bone turnover, P1NP and CTX and vitamin D concentration were assessed. After co varying for height, weight and baseline bone measurements, the supplemented group displayed greater post-intervention bone properties at the 66% proximal site with cortical content (mgmm) 6.6% greater (p<0.001), cortical area (mm(2)) 5.9% larger (p<0.001), cortical density (mgcm(2)) 1.3% greater (p=0.001), and total area (mm(2)) 4% larger (p=0.003). No other between group differences in bone variables were observed. Blood analysis indicated higher vitamin D levels (18.1%, p=0.014) and lower CTx (ng/L) (-24.8%, p=0.011) in the supplemented group with no differences observed in P1NP. This is the first randomised controlled trial to examine the efficacy of calcium and vitamin D supplementation in improving bone properties in a highly vulnerable, young athletic, weight-restricted population. Results using pQCT indicate beneficial effects of supplementation on bone properties in as little as six months. Although the study size is small, this intervention appears promising as a strategy for improving bone health in young athletes in weight-restricted sports. PMID- 26362228 TI - Nonoperative management of rectal cancer after chemoradiation opposed to resection after complete clinical response. A comparative study. AB - INTRODUCTION: Surgery is the standard treatment of rectal cancer after neoadjuvant therapy. Some authors advocate a nonoperative management (NOM) after complete clinical response (cCR) following chemoradiotherapy (CRT). We compare our results with NOM to standard resection in a retrospective analysis. METHODS: Rectal adenocarcinomas submitted to NOM after CRT between September 2002 and December 2013 were compared to surgical patients that had pathological complete response (pCR) during the same period. Endpoints were Overall Survival (OS), Disease Free Survival (DFS), Local Relapse (LR) and Distant Relapse (DR). RESULTS: Forty-two NOM patients compared to 69 pCR patients operated after a median interval of 35 weeks after CRT. NOM tumors were distal (83.3% vs 59.4%, p = 0.011), less obstructive (26.2% vs 54.4%, p = 0.005) and had a lower digital rectal score (p = 0.024). Twelve (28.0%) recurrences in NOM group and eight (11.5%) in the surgical group occurred after a follow-up of 47.7 and 46.7 months respectively. Isolated LR occurred in five (11%) NOM patients and one (1.4%) in the surgical group. Four (80%) LR were surgically salvaged in NOM group. No difference in OS was found (71.6% vs 89.9%, p = 0.316) but there was a higher DFS favoring surgical group (60.9% vs 82.8%, p = 0.011). Distal tumors had worse OS compared to proximal tumors in surgical group (5-year OS of 85.5% vs 96.2%, p = 0.038). CONCLUSION: The NOM achieved OS comparable to surgical treatment and spared patients from surgical morbidity but it resulted in more recurrences. This approach cannot be advocated routinely and controlled trials are warranted. PMID- 26362229 TI - Optimal escapement in stage-structured fisheries with environmental stochasticity. AB - Stage-structured population models are commonly used to understand fish population dynamics and additionally for stock assessment. Unfortunately, there is little theory on the optimal harvest of stage-structured populations, especially in the presence of stochastic fluctuations. In this paper, we find closed form optimal equilibrium escapement policies for a three-dimensional, discrete-time, stage-structured population model with linear growth, post-harvest nonlinear recruitment, and stage-specific pricing and extend the analytic results to structured populations with environmental stochasticity. When only fishing reproductive adults, stochasticity does not affect optimal escapement policies. However, when harvesting immature fish, the addition of stochasticity can increase or decrease optimal escapement depending on the second and third derivative of the recruitment function. For logistic recruitment, stochasticity reduces optimal immature escapement by a multiplicative factor of one over one plus the variance of the environmental noise. Using hard clam, Mercenaria mercenaria, as an example and assuming Beverton-Holt recruitment, we show that optimal fishing of hard clam targets the immature stage class exclusively and that environmental stochasticity increases optimal escapement for low discount rates and decreases optimal escapement for high discount rates. PMID- 26362230 TI - Comparison of mathematical frameworks for modeling erythropoiesis in the context of malaria infection. AB - Malaria is an infectious disease present all around the globe and responsible for half a million deaths per year. A within-host model of this infection requires a framework capable of properly approximating not only the blood stage of the infection but also the erythropoietic process that is in charge of overcoming the malaria induced anemia. Within this context, we compare ordinary differential equations (ODEs) with and without age classes, delayed differential equations (DDEs), and discrete recursive equations (DREs) with age classes. Results show that ODEs without age classes are fair approximations that do not provide a crisp temporal representation of the processes involved, and inclusion of age classes only mitigates the problem to some degree. DDEs perform well with respect to generating the essentially fixed delay between cell production and cell removal due to age, but the inclusion of any other processes, such as sudden blood loss, becomes cumbersome. The framework that was found to perform best in representing the dynamics of red blood cells during malaria infection is a DRE with age classes. In this model structure, the amount of time a cell remains alive is easily controlled, and the addition of age dependent or independent processes is straightforward. All events that populations of cells face during their lifespan, like growth or adaptation in differentiation or maturation rate, are properly represented in this framework. PMID- 26362231 TI - A multiobjective optimization approach for combating Aedes aegypti using chemical and biological alternated step-size control. AB - Dengue epidemics, one of the most important viral disease worldwide, can be prevented by combating the transmission vector Aedes aegypti. In support of this aim, this article proposes to analyze the Dengue vector control problem in a multiobjective optimization approach, in which the intention is to minimize both social and economic costs, using a dynamic mathematical model representing the mosquitoes' population. It consists in finding optimal alternated step-size control policies combining chemical (via application of insecticides) and biological control (via insertion of sterile males produced by irradiation). All the optimal policies consists in apply insecticides just at the beginning of the season and, then, keep the mosquitoes in an acceptable level spreading into environment a few amount of sterile males. The optimization model analysis is driven by the use of genetic algorithms. Finally, it performs a statistic test showing that the multiobjective approach is effective in achieving the same effect of variations in the cost parameters. Then, using the proposed methodology, it is possible to find, in a single run, given a decision maker, the optimal number of days and the respective amounts in which each control strategy must be applied, according to the tradeoff between using more insecticide with less transmission mosquitoes or more sterile males with more transmission mosquitoes. PMID- 26362232 TI - Monte Carlo methods for light propagation in biological tissues. AB - Light propagation in turbid media is driven by the equation of radiative transfer. We give a formal probabilistic representation of its solution in the framework of biological tissues and we implement algorithms based on Monte Carlo methods in order to estimate the quantity of light that is received by a homogeneous tissue when emitted by an optic fiber. A variance reduction method is studied and implemented, as well as a Markov chain Monte Carlo method based on the Metropolis-Hastings algorithm. The resulting estimating methods are then compared to the so-called Wang-Prahl (or Wang) method. Finally, the formal representation allows to derive a non-linear optimization algorithm close to Levenberg-Marquardt that is used for the estimation of the scattering and absorption coefficients of the tissue from measurements. PMID- 26362233 TI - Short-term effectiveness of spinal manipulative therapy versus functional technique in patients with chronic nonspecific low back pain: a pragmatic randomized controlled trial. AB - BACKGROUND CONTEXT: Chronic low back pain (LBP) is a prevalent condition associated with pain, disability, decreased quality of life, and fear of movement. To date, no studies have compared the effectiveness of spinal manipulation and functional technique for the management of this population. PURPOSE: This study aimed to compare the effectiveness of spinal manipulation and functional technique on pain, disability, kinesiophobia, and quality of life in patients with chronic LBP. STUDY DESIGN/SETTING: A single-blind pragmatic randomized controlled trial conducted in a university research clinic was carried out. PATIENT SAMPLE: Sixty-two patients (62% female, age: 45+/-7) with chronic LBP comprised the patient sample. OUTCOME MEASURES: Data on disability (Roland Morris Disability Questionnaire [RMQ], Oswestry Low Back Pain Disability Index [ODI]), pain intensity (Numerical Pain Rate Scale [NPRS]), fear of movement (Tampa Scale of Kinesiophobia [TSK]), quality of life (Short Form-36 [SF-36] quality of life questionnaire), isometric resistance of abdominal muscles (McQuade test), and spinal mobility in flexion (finger-to-floor distance) were collected at baseline immediately after the intervention phase and at 1 month postintervention by an assessor blinded to group allocation of the patients. METHODS: Patients were randomly assigned to the spinal manipulative therapy group or the functional technique group and received three once-weekly sessions. RESULTS: In comparison to patients receiving functional technique, those receiving spinal manipulation experienced statistically, although not clinically, significant greater reductions in terms of RMQ (standardized mean difference in score changes between groups at post-treatment: 0.1; at 1 month: 0.1) and ODI (post-treatment: 2.9; at 1 month: 1.4). Linear longitudinal analysis showed a significant improvement in both groups over time for RMQ (manipulative: F=68.51, p<.001; functional: F=28.58, p<.001) and ODI (manipulative: F=104.66, p<.001; functional: F=32.15, p=.001). However, significant treatment-by-time interactions were not detected for pain intensity (p=.488), TSK (p=.552), any domains of the SF-36 quality of life questionnaire (p<=.164), McQuade test (p=.512), and finger to-floor distance (p=.194). Differences between and within groups were not clinically meaningful in any of the reported measures. CONCLUSIONS: In comparison to functional technique, spinal manipulative therapy showed greater reduction in disability in patients with chronic LBP, but not in terms of pain, fear of movement, quality of life, isometric resistance of trunk flexors, or spinal mobility. However, differences in disability were not clinically meaningful; therefore, spinal manipulative therapy did not result in any clinically important short-term benefits over functional technique therapy. In addition, as neither group met the threshold for minimum clinically important difference following treatment, neither treatment resulted in a clinically meaningful benefit. PMID- 26362234 TI - Immuno-chemistry of hydroxyl radical modified GAD-65: A possible role in experimental and human diabetes mellitus. AB - The repertoire of known auto-antigens is limited to a very small proportion of all human proteins, and the reason why only some proteins become auto-antigens is unclear. The 65 kDa isoform of the enzyme glutamic acid decarboxylase (GAD-65) is a major auto-antigen in type I diabetes, and in various neurological diseases. Most patients with type I diabetes (70-80%) have auto-antibodies against GAD-65, which often appear years before clinical onset of the autoimmune diabetes. Thus, the aim of the study is to focus on the immunogenicity of GAD65 and its reactive oxygen species (ROS) conformer in STZ-induced diabetic rats and on human diabetic patients. In the present study, GAD-65 was modified by hydroxyl radical following Fenton's reaction. The modifications in the structure of the GAD-65 are supported by UV-vis and fluorescence spectral studies. Immunogenicity of both native and hydroxyl radical modified GAD-65 (ROS-GAD-65) was studied in experimental rabbits and was confirmed by inducing type I diabetes in experimental male albino rats using streptozotocin (45 mg/kg). We found that ROS-GAD-65 was a better immunogen as compared to the native GAD-65. A considerable high binding to ROS-GAD-65 was observed as compared to native GAD-65 in both the serum antibodies from diabetes animal models and as well as in the serum samples of type I diabetes. Hydrogen peroxide under the exposure of UV light produces hydroxyl radical (.OH) which is most potent oxidant, and could cause protein damage (GAD-65) to the extent of generating neo-epitopes on the molecule, thus making it immunogenic. PMID- 26362235 TI - Platelet rich plasma versus corticosteroid injection for plantar fasciitis: A comparative study. AB - INTRODUCTION: Intractable plantar fasciitis can be a difficult condition to treat. Early results of platelet rich plasma (PRP) injection have been promising. We compared PRP to traditional cortisone injection in the treatment of chronic cases of plantar fasciitis resistant to traditional nonoperative management. The aim of the study was to compare the efficacy of PRP to that of Steroid at 3, 6 and 12 months after injection. METHODS: 60 heels with intractable plantar fasciitis who had failed conservative treatment were randomised to receive either PRP or Steroid injection. All patients were assessed with the Roles-Maudsley (RM) Score, Visual Analogue Score (VAS) for pain and the American Orthopaedic Foot and Ankle Society (AOFAS) score. Data was collected prospectively on the cohort, pre treatment, at 3, 6 and 12 months post injection and the results were compared. RESULTS: Pre-injection, the two groups were well matched with no statistically significant difference. At 3 months, all three outcome scores had significantly improved from their pretreatment level in both groups. The scores in the Steroid arm were marginally better than in the PRP arm, but this difference was not statistically significant. At 6 months, there was no statistically significant difference between the two groups, though there was a trend for the PRP scores to become better than the Steroid scores. At 12 months, the RM, VAS and AOFAS scores in the PRP arm (1.9, 3.3 and 88.5) were significantly better than the Steroid arm (2.6, 5.3 and 75) with P values of .013, .028 and .033, respectively. CONCLUSIONS: PRP is as effective as Steroid injection at achieving symptom relief at 3 and 6 months after injection, for the treatment of plantar fasciitis, but unlike Steroid, its effect does not wear off with time. At 12 months, PRP is significantly more effective than Steroid, making it better and more durable than cortisone injection. PMID- 26362236 TI - The effect of orthotics on intersegmental foot kinematics and the EMG activity of select lower leg muscles. AB - BACKGROUND: Persons with exertional related leg pain are managed using orthoses. This study aimed to determine the effectiveness of two orthoses in altering foot motion and muscle activity in symptomatic individuals. METHODS: 52 subjects with lower extremity pain complaints of a non-traumatic, mechanical origin received one of two orthoses. Foot kinematics and EMG activity were recorded while treadmill walking in 3 footwear conditions. The peak EMG activity of the sandal and sandal orthotic trials (normalized to peak barefoot values) and foot motion during 4 subphases of stance were obtained. Using a multivariate multilevel model via linear mixed models, the effect of orthoses within these phases on motion and EMG was determined. RESULTS: An effect of orthotic type was not present for any of the rearfoot or forefoot motions (p>.10). A significant effect of footwear and orthotic type on first ray motion (p<.05) during subphases 2 and 4 was seen. During subphase 4 an interaction effect between footwear condition and orthotic type on tibialis posterior EMG activity (p=.036) was present. CONCLUSION: Orthoses are unable to control rear or midfoot motion but appear to control first ray motion and during late stance, affect tibialis posterior muscle activity. Public trials registry number: NCRT02143947. PMID- 26362237 TI - 1st metatarsophalangeal joint fusion: A comparison of non-union and gender differences between locking and non-locking plating systems. AB - BACKGROUND: Fusion of the first metatarsophalangeal joint (1st MTPJ) is a common surgical procedure used to treat a variety of diseases and deformities of the forefoot. Fixation methods vary and typically fusion rates are good. OBJECTIVES: The objectives of the study are to demonstrate whether there is any advantage to using locking as opposed to non-locking plates for 1st MTPJ fusion. Additionally the study aims to determine whether there is any difference in non-union rates according to gender. METHODS: One hundred and seventy two consecutive 1st MTPJ fusions were performed for 153 patients. 40 patients (23%) were male and 132 (77%) female. Twenty patients received Hallu-fixTM plates, 76 CharlotteTM plates and 76 AnchorageTM plates. Postoperative radiographs were reviewed for non-union. Failure rates were compared using Fisher's exact tests (p=0.05). RESULTS: Twelve (6.9%) non-unions were identified. The difference in failure rates between all systems was not statistically significant. However, the difference in fusion rates between males (17.5%) and females (3.8%) was significant. CONCLUSION: This study finds that 1st MTPJ fusion is an effective method to treat diseases of the 1st MTPJ. Locking plates may offer better fusion rates than their non-locking counterparts. This is especially evident in male patients. PMID- 26362238 TI - First metatarsophalangeal arthroscopy in patients with post-traumatic hallux valgus. AB - Post-traumatic hallux valgus is relatively rare and has been reported after rupture of the medial collateral ligament of the first metatarsophalangeal (MTP 1) joint; Lisfranc joint injury; turf toe injury; medial plantar nerve entrapment secondary to tibial fracture or first metatarsal fracture. Post-traumatic hallux valgus after medial collateral ligament injury has a high incidence of MTP-1 pathology. Detailed history and clinical examination can facilitate differentiation of the source(s) of the patient's symptoms and assist accurate formulation of the surgical plan. First, MTP arthroscopy is a feasible diagnostic and therapeutic tool to manage the MTP-1 joint pain in hallux valgus following injury to the MTP-1 joint. PMID- 26362240 TI - Angiolymphoid hyperplasia with eosinophilia of the head arising within the aponeurosis. PMID- 26362239 TI - Crystal structure of the Mycobacterium tuberculosis transcriptional regulator Rv0302. AB - Mycobacterium tuberculosis is a pathogenic bacterial species, which is neither Gram positive nor Gram negative. It has a unique cell wall, making it difficult to kill and conferring resistance to antibiotics that disrupt cell wall biosynthesis. Thus, the mycobacterial cell wall is critical to the virulence of these pathogens. Recent work shows that the mycobacterial membrane protein large (MmpL) family of transporters contributes to cell wall biosynthesis by exporting fatty acids and lipidic elements of the cell wall. The expression of the Mycobacterium tuberculosis MmpL proteins is controlled by a complicated regulatory network system. Here we report crystallographic structures of two forms of the TetR-family transcriptional regulator Rv0302, which participates in regulating the expression of MmpL proteins. The structures reveal a dimeric, two domain molecule with architecture consistent with the TetR family of regulators. Comparison of the two Rv0302 crystal structures suggests that the conformational changes leading to derepression may be due to a rigid body rotational motion within the dimer interface of the regulator. Using fluorescence polarization and electrophoretic mobility shift assays, we demonstrate the recognition of promoter and intragenic regions of multiple mmpL genes by this protein. In addition, our isothermal titration calorimetry and electrophoretic mobility shift experiments indicate that fatty acids may be the natural ligand of this regulator. Taken together, these experiments provide new perspectives on the regulation of the MmpL family of transporters. PMID- 26362241 TI - Pain management during radiotherapy and radiochemotherapy in oropharyngeal cancer patients: single-institution experience. AB - AIM OF THE STUDY: Radiotherapy (RT) is a radical therapeutic option for patients with oropharyngeal cancer (OPC). It induces an acute postradiation reaction that may cause significant pain. The aim of this study was to analyse pain occurrence and intensity, as well as type and effectiveness of analgesic treatment, in OPC patients undergoing RT or radiochemotherapy (RT-CT). MATERIAL AND METHODS: Retrospective data were obtained for 42 OPC patients at clinical stages I-IVA, treated with adjuvant RT or RT-CT or definite RT or RT-CcT at the Comprehensive Cancer Center in Bialystok, Poland. Pain intensity and type of analgesic treatment during the therapy were analysed and compared with the intensity of the radiation-induced acute reaction, assessed weekly according to the Dische score. RESULTS: Thirty-nine (92.9%) patients received analgesic treatment. Analgesic therapy was started in 27 (64.3%) patients with administration of non-steroidal anti-inflammatory drugs (NSAIDs) and/or paracetamol, in seven (16.7%) with mild opioids and in five (11.9%) with strong opioids. Strong opioids were used during therapy in 21 (50%) patients. Co-analgesics were administered to six patients. Breakthrough pain was observed in 10 (23.8%) patients. CONCLUSIONS: High incidence of pain during RT and RT-CT calls for increased awareness of the importance of pain monitoring and treatment during RT of OPC patients. The analgesic treatment had to be adjusted individually. PMID- 26362243 TI - Ischaemic pancreatitis and pseudocyst: a rare complication of embolization of gastroduodenal artery aneurysm. PMID- 26362242 TI - Quantitative susceptibility mapping of the midbrain in Parkinson's disease. AB - BACKGROUND: Parkinson's disease (PD) is marked pathologically by dopamine neuron loss and iron overload in the substantia nigra pars compacta. Midbrain iron content is reported to be increased in PD based on magnetic resonance imaging (MRI) R2* changes. Because quantitative susceptibility mapping is a novel MRI approach to measure iron content, we compared it with R2* for assessing midbrain changes in PD. METHODS: Quantitative susceptibility mapping and R2* maps were obtained from 47 PD patients and 47 healthy controls. Midbrain susceptibility and R2* values were analyzed by using both voxel-based and region-of-interest approaches in normalized space, and analyzed along with clinical data, including disease duration, Unified Parkinson's Disease Rating Scale (UPDRS) I, II, and III subscores, and levodopa-equivalent daily dosage. All studies were done while PD patients were "on drug." RESULTS: Compared with controls, PD patients showed significantly increased susceptibility values in both right (cluster size = 106 mm(3)) and left (164 mm(3)) midbrain, located ventrolateral to the red nucleus that corresponded to the substantia nigra pars compacta. Susceptibility values in this region were correlated significantly with disease duration, UPDRS II, and levodopa-equivalent daily dosage. Conversely, R2* was increased significantly only in a much smaller region (62 mm(3)) of the left lateral substantia nigra pars compacta and was not significantly correlated with clinical parameters. CONCLUSION: The use of quantitative susceptibility mapping demonstrated marked nigral changes that correlated with clinical PD status more sensitively than R2*. These data suggest that quantitative susceptibility mapping may be a superior imaging biomarker to R2* for estimating brain iron levels in PD. PMID- 26362244 TI - Biopolymeric nanocomposites with enhanced interphases. AB - Ultrathin and robust nanocomposite membranes were fabricated by incorporating graphene oxide (GO) sheets into a silk fibroin (SF) matrix by a dynamic spin assisted layer-by-layer assembly (dSA-LbL). We observed that in contrast to traditional SA-LbL reported earlier fast solution removal during dropping of solution on constantly spinning substrates resulted in largely unfolded biomacromolecules with enhanced surface interactions and suppressed nanofibril formation. The resulting laminated nanocomposites possess outstanding mechanical properties, significantly exceeding those previously reported for conventional LbL films with similar composition. The tensile modulus reached extremely high values of 170 GPa, which have never been reported for graphene oxide-based nanocomposites, the ultimate strength was close to 300 MPa, and the toughness was above 3.4 MJ m(-3). The failure modes observed for these membranes suggested the self-reinforcing mechanism of adjacent graphene oxide sheets with strong 2 nm thick silk interphase composed mostly from individual backbones. This interphase reinforcement leads to the effective load transfer between the graphene oxide components in reinforced laminated nanocomposite materials with excellent mechanical strength that surpasses those known today for conventional flexible laminated carbon nanocomposites from graphene oxide and biopolymer components. PMID- 26362245 TI - Effects of compassionate thinking on negative emotions. AB - The present study compared the effect of compassionate thinking with other methods traditionally used in cognitive behavioural therapy (cognitive reappraisal, responsibility reattribution, and self-deflection). An instructional manipulation was used, and 207 undergraduate students were randomly assigned to one of these thinking styles or a control condition. The results revealed that participants who engaged in compassionate thinking and cognitive reappraisal reported significantly lower levels of negative emotions compared to those in the responsibility reattribution and control conditions. Furthermore, results of hierarchical regression analyses suggested that habitual use of self-compassion reduced negative emotions in all conditions. These findings suggest that self compassion and reappraisal reduce negative emotions more than reattribution and self-deflection. PMID- 26362246 TI - Association between the severity of coronary artery stenosis and the combination of the difference in blood pressure between arms and brachial-ankle pulse wave velocity. AB - BACKGROUND: A difference in systolic blood pressure (SBP) >=10 mmHg between the arms is associated with an increased risk of coronary artery disease (CAD) and mortality in high-risk patients. METHODS AND RESULTS: Four hundred and fourteen patients were divided into three groups according to the percent most severe luminal narrowing of a coronary artery as diagnosed by coronary computed tomography angiography: no or mild coronary stenosis (0-49%), moderate stenosis (50-69%) and severe stenosis (>=70%) groups. The relative difference in SBP between arms in the severe group was significantly lower than those in the no or mild and moderate groups. The brachial-ankle pulse wave velocity (baPWV) significantly increased as the severity of coronary stenosis increased. We confirmed that severe coronary stenosis was independently associated with both the relative difference in SBP between arms and baPWV, in addition to age, gender, hypertension, dyslipidemia, diabetes mellitus and ankle-brachial index by a logistic regression analysis. The group with a relative difference in SBP between arms of <1 mmHg and baPWV >= 1613 cm/s showed a higher percentage of patients with severe coronary stenosis than groups that met neither or only one of these criteria. CONCLUSION: The combination of the relative difference in SBP between arms and baPWV may be a more effective approach for the non-invasive assessment of the severity of CAD. PMID- 26362247 TI - Squaring the round: An unusual progressive graphomotor impairment with post mortem findings. AB - Investigations of neurodegenerative disorders may reveal functional relationships in the cognitive system. C.S. was a 63-year-old right-handed man with post-mortem confirmed Pick's disease with a range of progressive impairments including non fluent aphasia, speech, limb, oculomotor, and buccofacial apraxia, but mostly intact intelligence, perception, orientation, memory, semantics, and phonology. During progression, agrammatism in writing with impairments in syntactic comprehension emerged in parallel with an unusual graphomotor deficit in drawing and writing, with an increasing deterioration of graphic short-term memory. We investigated C.S.'s graphomotor deficit longitudinally using tests of writing and drawing on letters, words, and sentences and drawing to command and copying. We also tested C.S.'s short-term graphemic buffer experimentally. Analysis showed deficits on selective aspects of graphomotor implementation of writing and drawing, mainly affecting the production of circles and curves, but not short straight lines in drawing and writing, and graphomotor short-term memory, which paralleled impairments of written syntax and syntactic comprehension. We believe this to be the first detailed analysis of such an unusual progressive impairment in graphomotor production, which may be related to problems with agrammatic agraphia and impairments affecting shared components of cognition reflecting damage to shared neural networks. Alternatively, they may simply reflect the effects of coincidental damage to separate mechanisms responsible for aspects of writing, drawing, and syntactic processing. Longitudinal investigations of emerging deficits in progressive conditions like C.S.'s provides an opportunity to examine the progressive emergence of symptoms in an individual with multiple progressive impairments as they appear and examine putative relationships between them. PMID- 26362248 TI - Viscoelastic substance in prefilled syringe as an etiology of Toxic Anterior Segment Syndrome. AB - CONTEXT: Toxic Anterior Segment Syndrome (TASS) is an acute postoperative inflammatory reaction in which a noninfectious substance enters the anterior segment and induces toxic damage to the intraocular tissues. OBJECTIVE: To present etiologic investigation of two consecutive clusters of TASS. TASS outbreak and investigation: This paper presents two consecutive clusters of TASS in 15 of the 24 uneventful surgeries and the investigation carried out to find the etiology. After the occurrence of first cluster of TASS, sterilization related etiology was explored; however, we did not find any lacunae in the sterilization and cleaning process in the operating theater (OT). Nevertheless, multiple changes in cleaning process were implemented. Still a second cluster of TASS was encountered in the following session of OT. Several other factors which include preservatives, hand gloves, intraocular lenses, medications/solutions, intraocular penetration of topically administered drugs, and viscoelastics were investigated as the possible etiology of the second consecutive cluster of TASS; however, most of them were ruled out. The newly introduced viscoelastic I-visc(r) 1.4% sodium hyaluronate (I medical, i-Medical Ophthalmic International GmbH, Heidelberg, Germany) was thought to be the most likely cause and was replaced with previously in use sodium hyaluronate 1.5% and lidocaine hydrochloride 1% (Visthesia, CZ, Germany) in the following session of OT. No further TASS incident was encountered after replacing the viscoelastic. CONCLUSION: Investigation revealed that 1.4% sodium hyaluronate in prefilled syringe (PFS) (I-visc(r) 1.4%) was the etiologic factor of two consecutive clusters of TASS. While TASS due to residual denatured ophthalamic viscosurgical devices (OVDs) is a common knowledge, current study brings out that even disposable viscoelastic material supplied in PFSs can be an etiology of TASS. It is important to recognize that contamination of OVDs with endotoxins can occur at the time of manufacturing. Therefore, in the absence of appropriate guidelines for ophthalmic preparations, endotoxin limit for medical preparations (i.e. <0.5 endotoxin units/ml) must be considered during OVD manufacture. PMID- 26362249 TI - Oral and inhaled glucocorticoid use and risk of Achilles or biceps tendon rupture: a population-based case-control study. AB - BACKGROUND: Tendinotoxicity of glucocorticoids (GC) has been shown, but evidence on how this translates into clinical practice remains scarce. OBJECTIVES: To explore the association between oral or inhaled GC use and the risk of Achilles or biceps tendon rupture (ATR/BTR). METHODS: We identified patients aged 18 to 89 years with incident ATR or BTR (1995-2013) for a matched (1:4) case-control analysis using the UK-based Clinical Practice Research Datalink. We stratified oral GC use by indication, timing and duration of use, continuous versus intermittent use, cumulative dose, and average daily dose. We stratified inhaled GC use by timing and number of prescriptions. RESULTS: Among 8,202 cases, we observed increased odds ratios (ORs) around 3.0 for continuous oral GC use, which declined shortly after therapy cessation (similarly across indications). Odds ratios increased with average daily dose (>= 10 mg/day, OR 4.05, 95% CI 2.32 7.08) and were elevated after one cycle of high-dose oral GC (>= 20 mg/day). There was no effect of inhaled GC at any level of exposure. CONCLUSION: Our results provide evidence that oral GC therapy increases the risk of tendon rupture in a dose-response relationship. A single short-term high-dose GC treatment course may be sufficient transiently to increase the risk of tendon rupture. PMID- 26362251 TI - A systematic screening to identify de novo mutations causing sporadic early-onset Parkinson's disease. AB - Despite the many advances in our understanding of the genetic basis of Mendelian forms of Parkinson's disease (PD), a large number of early-onset cases still remain to be explained. Many of these cases, present with a form of disease that is identical to that underlined by genetic causes, but do not have mutations in any of the currently known disease-causing genes. Here, we hypothesized that de novo mutations may account for a proportion of these early-onset, sporadic cases. We performed exome sequencing in full parent-child trios where the proband presents with typical PD to unequivocally identify de novo mutations. This approach allows us to test all genes in the genome in an unbiased manner. We have identified and confirmed 20 coding de novo mutations in 21 trios. We have used publicly available population genetic data to compare variant frequencies and our independent in-house dataset of exome sequencing in PD (with over 1200 cases) to identify additional variants in the same genes. Of the genes identified to carry de novo mutations, PTEN, VAPB and ASNA1 are supported by various sources of data to be involved in PD. We show that these genes are reported to be within a protein-protein interaction network with PD genes and that they contain additional rare, case-specific, mutations in our independent cohort of PD cases. Our results support the involvement of these three genes in PD and suggest that testing for de novo mutations in sporadic disease may aid in the identification of novel disease-causing genes. PMID- 26362250 TI - miR-132/212 deficiency impairs tau metabolism and promotes pathological aggregation in vivo. AB - Alzheimer's disease (AD) and related tauopathies comprise a large group of neurodegenerative diseases associated with the pathological aggregation of tau protein. While much effort has focused on understanding the function of tau, little is known about the endogenous mechanisms regulating tau metabolism in vivo and how these contribute to disease. Previously, we have shown that the microRNA (miRNA) cluster miR-132/212 is downregulated in tauopathies such as AD. Here, we report that miR-132/212 deficiency in mice leads to increased tau expression, phosphorylation and aggregation. Using reporter assays and cell-based studies, we demonstrate that miR-132 directly targets tau mRNA to regulate its expression. We identified GSK-3beta and PP2B as effectors of abnormal tau phosphorylation in vivo. Deletion of miR-132/212 induced tau aggregation in mice expressing endogenous or human mutant tau, an effect associated with autophagy dysfunction. Conversely, treatment of AD mice with miR-132 mimics restored in part memory function and tau metabolism. Finally, miR-132 and miR-212 levels correlated with insoluble tau and cognitive impairment in humans. These findings support a role for miR-132/212 in the regulation of tau pathology in mice and humans and provide new alternatives for therapeutic development. PMID- 26362252 TI - Myofibrillar disruption and RNA-binding protein aggregation in a mouse model of limb-girdle muscular dystrophy 1D. AB - Limb-girdle muscular dystrophy type 1D (LGMD1D) is caused by dominantly inherited missense mutations in DNAJB6, an Hsp40 co-chaperone. LGMD1D muscle has rimmed vacuoles and inclusion bodies containing DNAJB6, Z-disc proteins and TDP-43. DNAJB6 is expressed as two isoforms; DNAJB6a and DNAJB6b. Both isoforms contain LGMD1D mutant residues and are expressed in human muscle. To identify which mutant isoform confers disease pathogenesis and generate a mouse model of LGMD1D, we evaluated DNAJB6 expression and localization in skeletal muscle as well as generating DNAJB6 isoform specific expressing transgenic mice. DNAJB6a localized to myonuclei while DNAJB6b was sarcoplasmic. LGMD1D mutations in DNAJB6a or DNAJB6b did not alter this localization in mouse muscle. Transgenic mice expressing the LGMD1D mutant, F93L, in DNAJB6b under a muscle-specific promoter became weak, had early lethality and developed muscle pathology consistent with myopathy after 2 months; whereas mice expressing the same F93L mutation in DNAJB6a or overexpressing DNAJB6a or DNAJB6b wild-type transgenes remained unaffected after 1 year. DNAJB6b localized to the Z-disc and DNAJB6b-F93L expressing mouse muscle had myofibrillar disorganization and desmin inclusions. Consistent with DNAJB6 dysfunction, keratin 8/18, a DNAJB6 client also accumulated in DNAJB6b-F93L expressing mouse muscle. The RNA-binding proteins hnRNPA1 and hnRNPA2/B1 accumulated and co-localized with DNAJB6 at sarcoplasmic stress granules suggesting that these proteins maybe novel DNAJB6b clients. Similarly, hnRNPA1 and hnRNPA2/B1 formed sarcoplasmic aggregates in patients with LGMD1D. Our data support that LGMD1D mutations in DNAJB6 disrupt its sarcoplasmic function suggesting a role for DNAJB6b in Z-disc organization and stress granule kinetics. PMID- 26362253 TI - Glucocerebrosidase deficiency accelerates the accumulation of proteinase K resistant alpha-synuclein and aggravates neurodegeneration in a Drosophila model of Parkinson's disease. AB - Alpha-synuclein (alphaSyn) plays a central role in the pathogenesis of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Recent multicenter genetic studies have revealed that mutations in the glucocerebrosidase 1 (GBA1) gene, which are responsible for Gaucher's disease, are strong risk factors for PD and DLB. However, the mechanistic link between the functional loss of glucocerebrosidase (GCase) and the toxicity of alphaSyn in vivo is not fully understood. In this study, we employed Drosophila models to examine the effect of GCase deficiency on the neurotoxicity of alphaSyn and its molecular mechanism. Behavioral and histological analyses showed that knockdown of the Drosophila homolog of GBA1 (dGBA1) exacerbates the locomotor dysfunction, loss of dopaminergic neurons and retinal degeneration of alphaSyn-expressing flies. This phenotypic aggravation was associated with the accumulation of proteinase K (PK) resistant alphaSyn, rather than with changes in the total amount of alphaSyn, raising the possibility that glucosylceramide (GlcCer), a substrate of GCase, accelerates the misfolding of alphaSyn. Indeed, in vitro experiments revealed that GlcCer directly promotes the conversion of recombinant alphaSyn into the PK resistant form, representing a toxic conformational change. Similar to dGBA1 knockdown, knockdown of the Drosophila homolog of beta-galactosidase (beta-Gal) also aggravated locomotor dysfunction of the alphaSyn flies, and its substrate GM1 ganglioside accelerated the formation of PK-resistant alphaSyn. Our findings suggest that the functional loss of GCase or beta-Gal promotes the toxic conversion of alphaSyn via aberrant interactions between alphaSyn and their substrate glycolipids, leading to the aggravation of alphaSyn-mediated neurodegeneration. PMID- 26362254 TI - Molecular analyses of juvenile granulosa cell tumors bearing AKT1 mutations provide insights into tumor biology and therapeutic leads. AB - Juvenile granulosa cell tumors (JGCTs) of the ovary are pediatric neoplasms representing 5% of all granulosa cell tumors (GCTs). Most GCTs are of adult type (AGCTs) and bear a mutation in the FOXL2 gene. The molecular basis of JGCTs is poorly understood, although mutations in the GNAS gene have been reported. We have detected in-frame duplications within the oncogene AKT1 in >60% of the JGCTs studied. Here, to evaluate the functional impact of these duplications and the existence of potential co-driver alterations, we have sequenced the transcriptome of four JGCTs and compared them with control transcriptomes. A search for gene variants detected only private alterations probably unrelated with tumorigenesis, suggesting that tandem duplications are the best candidates to underlie tumor formation in the absence of GNAS alterations. We previously showed that the duplications were specific to JGCTs. However, the screening of eight AGCTs samples without FOXL2 mutation showed the existence of an AKT1 duplication in one case, also having a stromal luteoma. The analysis of RNA-Seq data pinpointed a series of differentially expressed genes, involved in cytokine and hormone signaling and cell division-related processes. Further analyses pointed to the existence of a possible dedifferentiation process and suggested that most of the transcriptomic dysregulation might be mediated by a limited set of transcription factors perturbed by AKT1 activation. Finally, we show that commercially available AKT inhibitors can modulate the in vitro activity of various mutated forms. These results shed light on the pathogenesis of JGCTs and provide therapeutic leads for a targeted treatment. PMID- 26362255 TI - Two novel COLVI long chains in zebrafish that are essential for muscle development. AB - Collagen VI (COLVI), a protein ubiquitously expressed in connective tissues, is crucial for structural integrity, cellular adhesion, migration and survival. Six different genes are recognized in mammalians, encoding six COLVI-chains that assemble as two 'short' (alpha1, alpha2) and one 'long' chain (theoretically any one of alpha3-6). In humans, defects in the most widely expressed heterotrimer (alpha123), due to mutations in the COL6A1-3 genes, cause a heterogeneous group of neuromuscular disorders, collectively termed COLVI-related muscle disorders. Little is known about the function(s) of the recently described alpha4-6 chains and no mutations have been detected yet. In this study, we characterized two novel COLVI long chains in zebrafish that are most homologous to the mammalian alpha4 chain; therefore, we named the corresponding genes col6a4a and col6a4b. These orthologues represent ancestors of the mammalian Col6a4-6 genes. By in situ hybridization and RT-qPCR, we unveiled a distinctive expression kinetics for col6a4b, compared with the other col6a genes. Using morpholino antisense oligonucleotides targeting col6a4a, col6a4b and col6a2, we modelled partial and complete COLVI deficiency, respectively. All morphant embryos presented altered muscle structure and impaired motility. While apoptosis was not drastically increased, autophagy induction was defective in all morphants. Furthermore, motoneuron axon growth was abnormal in these morphants. Importantly, some phenotypical differences emerged between col6a4a and col6a4b morphants, suggesting only partial functional redundancy. Overall, our results further confirm the importance of COLVI in zebrafish muscle development and may provide important clues for potential human phenotypes associated with deficiency of the recently described COLVI-chains. PMID- 26362256 TI - FGFR2 mutation in 46,XY sex reversal with craniosynostosis. AB - Patients with 46,XY gonadal dysgenesis (GD) exhibit genital anomalies, which range from hypospadias to complete male-to-female sex reversal. However, a molecular diagnosis is made in only 30% of cases. Heterozygous mutations in the human FGFR2 gene cause various craniosynostosis syndromes including Crouzon and Pfeiffer, but testicular defects were not reported. Here, we describe a patient whose features we would suggest represent a new FGFR2-related syndrome, craniosynostosis with XY male-to-female sex reversal or CSR. The craniosynostosis patient was chromosomally XY, but presented as a phenotypic female due to complete GD. DNA sequencing identified the FGFR2c heterozygous missense mutation, c.1025G>C (p.Cys342Ser). Substitution of Cys342 by Ser or other amino acids (Arg/Phe/Try/Tyr) has been previously reported in Crouzon and Pfeiffer syndrome. We show that the 'knock-in' Crouzon mouse model Fgfr2c(C342Y/C342Y) carrying a Cys342Tyr substitution displays XY gonadal sex reversal with variable expressivity. We also show that despite FGFR2c-Cys342Tyr being widely considered a gain-of-function mutation, Cys342Tyr substitution in the gonad leads to loss of function, as demonstrated by sex reversal in Fgfr2c(C342Y/-) mice carrying the knock-in allele on a null background. The rarity of our patient suggests the influence of modifier genes which exacerbated the testicular phenotype. Indeed, patient whole exome analysis revealed several potential modifiers expressed in Sertoli cells at the time of testis determination in mice. In summary, this study identifies the first FGFR2 mutation in a 46,XY GD patient. We conclude that, in certain rare genetic contexts, maintaining normal levels of FGFR2 signaling is important for human testis determination. PMID- 26362257 TI - Vapb/Amyotrophic lateral sclerosis 8 knock-in mice display slowly progressive motor behavior defects accompanying ER stress and autophagic response. AB - Missense mutations (P56S) in Vapb are associated with autosomal dominant motor neuron diseases: amyotrophic lateral sclerosis and lower motor neuron disease. Although transgenic mice overexpressing the mutant vesicle-associated membrane protein-associated protein B (VAPB) protein with neuron-specific promoters have provided some insight into the toxic properties of the mutant proteins, their role in pathogenesis remains unclear. To identify pathological defects in animals expressing the P56S mutant VAPB protein at physiological levels in the appropriate tissues, we have generated Vapb knock-in mice replacing wild-type Vapb gene with P56S mutant Vapb gene and analyzed the resulting pathological phenotypes. Heterozygous P56S Vapb knock-in mice show mild age-dependent defects in motor behaviors as characteristic features of the disease. The homozygous P56S Vapb knock-in mice show more severe defects compared with heterozygous mice reflecting the dominant and dose-dependent effects of P56S mutation. Significantly, the knock-in mice demonstrate accumulation of P56S VAPB protein and ubiquitinated proteins in cytoplasmic inclusions, selectively in motor neurons. The mutant mice demonstrate induction of ER stress and autophagic response in motor neurons before obvious onset of behavioral defects, suggesting that these cellular biological defects might contribute to the initiation of the disease. The P56S Vapb knock-in mice could be a valuable tool to gain a better understanding of the mechanisms by which the disease arises. PMID- 26362258 TI - Accelerated reproductive aging in females lacking a novel centromere protein SYCP2L. AB - Menopause results from loss of ovarian function and marks the end of a woman's reproductive life. Alleles of the human SYCP2L locus are associated with age at natural menopause (ANM). SYCP2L is a paralogue of the synaptonemal complex protein SYCP2 and is expressed exclusively in oocytes. Here we report that SYCP2L localizes to centromeres of dictyate stage oocytes, which represent the limited pool of primordial oocytes that are formed perinatally and remain arrested till ovulation. Centromere localization of SYCP2L requires its C-terminal portion, which is missing in truncated variants resulting from low-frequency nonsense mutations identified in humans. Female mice lacking SYCP2L undergo a significantly higher progressive loss of oocytes with age compared with wild-type females and are less fertile. Specifically, the pool of primordial oocytes becomes more rapidly depleted in SYCP2L-deficient than in wild-type females, such that with aging, fewer oocytes undergo maturation in developing follicles. We find that a human SYCP2L intronic single nucleotide polymorphism (SNP) rs2153157, which is associated with ANM, changes the splicing efficiency of U12-type minor introns and may therefore regulate the steady-state amount of SYCP2L transcript. Furthermore, the more efficiently spliced allele of this intronic SNP in SYCP2L is associated with increased ANM. Our results suggest that SYCP2L promotes the survival of primordial oocytes and thus provide functional evidence for its association with ANM in humans. PMID- 26362259 TI - Web-Based Intervention for Teachers of Elementary Students With ADHD: Randomized Controlled Trial. AB - OBJECTIVE: To test the acceptability, satisfaction, and effectiveness of a web based intervention for teachers of elementary school-aged children with ADHD. METHOD: Elementary classroom teachers (N = 58), along with their students with ADHD, participated in a randomized controlled trial. The program consisted of six sessions that included evidence-based intervention strategies for reducing ADHD symptoms and impairment in the classroom setting. Teachers also had access to a moderated Discussion Board and an online ADHD coach. Questionnaire data were electronically collected from teachers and parents pre-intervention, post intervention (6 weeks), and after an additional 6-week follow-up. RESULTS: Intent to-treat analyses found significant improvements based on teacher (but not parent) reports of core ADHD symptoms and impairment for the Teacher Help for ADHD treatment group. Teachers reported a high level of acceptability and satisfaction. CONCLUSION: Web-based ADHD interventions have the potential to reduce the barriers to treatment utilization and implementation that are common problems for school-based ADHD interventions. PMID- 26362262 TI - The Frequency of Peripheral Blood CD4+FoxP3+ Regulatory T Cells in Women With Pre eclampsia and Those With High-risk Factors for Pre-eclampsia. AB - OBJECTIVE: We compared the frequency of peripheral blood Treg cells in women with pre-eclampsia (PE) and in those without, and investigated whether the frequency of Treg cells in women with high-risk factor for PE changed during pregnancy. METHODS: We examined the frequency of CD4+FoxP3+ Treg cells in the peripheral blood using flow cytometry. Eleven women with PE and 10 women without PE (controls) were included. Every control had any risk factors for PE, such as high blood pressure, bilateral notching or a past history of PE or gestational hypertension. Blood sampling was conducted 1-3 times in the controls. RESULTS: No significant differences were observed in the frequency of Treg cells between women with PE and the controls [mean +/- SE (%): 5.74 +/- 0.91 versus 5.48 +/- 0.94, p = 0.843]. In five controls with serial sampling, the frequency of Treg cells significantly decreased from 5.83 +/- 1.20 to 2.99 +/- 0.54 (p = 0.046) (week of the first sampling to that of the last sampling [mean +/- SD]: 21.5 +/- 1.6 weeks to 31.2 +/- 2.5 weeks). CONCLUSION: The frequency of Treg cells in women with PE was almost identical to that in the controls. The frequency of Treg cells in the controls was reduced by half from the second trimester to the third trimester. These results suggested that the levels of Treg cells in a high-risk pregnant cohort were decreased to those in women with PE in the third trimester irrespective of the occurrence of PE. PMID- 26362261 TI - A bacterial toxin and a nonenveloped virus hijack ER-to-cytosol membrane translocation pathways to cause disease. AB - A dedicated network of cellular factors ensures that proteins translocated into the endoplasmic reticulum (ER) are folded correctly before they exit this compartment en route to other cellular destinations or for secretion. When proteins misfold, selective ER-resident enzymes and chaperones are recruited to rectify the protein-misfolding problem in order to maintain cellular proteostasis. However, when a protein becomes terminally misfolded, it is ejected into the cytosol and degraded by the proteasome via a pathway called ER associated degradation (ERAD). Strikingly, toxins and viruses can hijack elements of the ERAD pathway to access the host cytosol and cause infection. This review focuses on emerging data illuminating the molecular mechanisms by which these toxic agents co-opt the ER-to-cytosol translocation process to cause disease. PMID- 26362263 TI - Public Perceptions of Doctors of Chiropractic: Results of a National Survey and Examination of Variation According to Respondents' Likelihood to Use Chiropractic, Experience With Chiropractic, and Chiropractic Supply in Local Health Care Markets. AB - OBJECTIVES: The purpose of this study was to determine whether general perceptions of doctors of chiropractic (DCs) varied according to likeliness to use chiropractic care, whether particular demographic characteristics were associated with chiropractic care use, and whether perception of DCs varied according to the per-capita supply of DCs in local health care markets. METHODS: We performed a secondary analysis of results from a 26-item nationally representative survey of 5422 members of The Gallup Panel that was conducted in the spring of 2015 (response rate, 29%) that sought to elicit the perceptions and use of DCs by US adults. We compared survey responses across: (1) respondents who had different likelihoods to use DCs for treatment of neck or back pain and (2) respondents who had different experiences using DCs. We linked respondents' zip codes to hospital referral regions for which we had the per-capita supply of DCs. Using the chi(2) test, we examined relationships between likeliness to use a DC, experience using a DC, respondent demographic variables, perceptions of DCs, and the per-capita supply of DCs in the local health care market. RESULTS: Most (61.4%) respondents believed that chiropractic care was effective at treating neck and back pain, 52.6% thought DCs were trustworthy, and 24.2% thought chiropractic care was dangerous; however, as respondents' likelihood to use a DC increased, perceptions of effectiveness and trustworthiness increased, and perceptions of danger decreased. Of all 5422 survey respondents, 744 or 13.7% indicated that they had seen a DC within the last 12 months. As one moved from distant to more recent experience using a DC, respondents were more likely to be female, married, white, and employed; those who had a distant history of using a DC were older and more likely to be retired than the other groups. A higher per capita supply of DCs was associated with higher utilization rates and showed a more favorable regard for DCs. CONCLUSIONS: US adults often use chiropractic care, generally regard DCs favorably, and largely perceive that chiropractic care is safe. Where there is a higher per-capita supply of DCs in the local health care market, utilization and positive perceptions of chiropractic are higher. PMID- 26362264 TI - BALB/c and C57BL/6 Mice Differ in Polyreactive IgA Abundance, which Impacts the Generation of Antigen-Specific IgA and Microbiota Diversity. AB - The interrelationship between IgAs and microbiota diversity is still unclear. Here we show that BALB/c mice had higher abundance and diversity of IgAs than C57BL/6 mice and that this correlated with increased microbiota diversity. We show that polyreactive IgAs mediated the entrance of non-invasive bacteria to Peyer's patches, independently of CX3CR1(+) phagocytes. This allowed the induction of bacteria-specific IgA and the establishment of a positive feedback loop of IgA production. Cohousing of mice or fecal transplantation had little or no influence on IgA production and had only partial impact on microbiota composition. Germ-free BALB/c, but not C57BL/6, mice already had polyreactive IgAs that influenced microbiota diversity and selection after colonization. Together, these data suggest that genetic predisposition to produce polyreactive IgAs has a strong impact on the generation of antigen-specific IgAs and the selection and maintenance of microbiota diversity. PMID- 26362265 TI - Tissue-Specific Distribution of iNKT Cells Impacts Their Cytokine Response. AB - Three subsets of invariant natural killer T (iNKT) cells have been identified, NKT1, NKT2, and NKT17, which produce distinct cytokines when stimulated, but little is known about their localization. Here, we have defined the anatomic localization and systemic distribution of these subsets and measured their cytokine production. Thymic NKT2 cells that produced interleukin-4 (IL-4) at steady state were located in the medulla and conditioned medullary thymocytes. NKT2 cells were abundant in the mesenteric lymph node (LN) of BALB/c mice and produced IL-4 in the T cell zone that conditioned other lymphocytes. Intravenous injection of alpha-galactosylceramide activated NKT1 cells with vascular access, but not LN or thymic NKT cells, resulting in systemic interferon-gamma and IL-4 production, while oral alpha-galactosylceramide activated NKT2 cells in the mesenteric LN, resulting in local IL-4 release. These findings indicate that the localization of iNKT cells governs their cytokine response both at steady state and upon activation. PMID- 26362266 TI - Magnitude and Kinetics of CD8+ T Cell Activation during Hyperacute HIV Infection Impact Viral Set Point. AB - CD8(+) T cells contribute to the control of HIV, but it is not clear whether initial immune responses modulate the viral set point. We screened high-risk uninfected women twice a week for plasma HIV RNA and identified 12 hyperacute infections. Onset of viremia elicited a massive HIV-specific CD8(+) T cell response, with limited bystander activation of non-HIV memory CD8(+) T cells. HIV specific CD8(+) T cells secreted little interferon-gamma, underwent rapid apoptosis, and failed to upregulate the interleukin-7 receptor, known to be important for T cell survival. The rapidity to peak CD8(+) T cell activation and the absolute magnitude of activation induced by the exponential rise in viremia were inversely correlated with set point viremia. These data indicate that rapid, high magnitude HIV-induced CD8(+) T cell responses are crucial for subsequent immune control of acute infection, which has important implications for HIV vaccine design. PMID- 26362267 TI - Interactive Big Data Resource to Elucidate Human Immune Pathways and Diseases. AB - Many functionally important interactions between genes and proteins involved in immunological diseases and processes are unknown. The exponential growth in public high-throughput data offers an opportunity to expand this knowledge. To unlock human-immunology-relevant insight contained in the global biomedical research effort, including all public high-throughput datasets, we performed immunological-pathway-focused Bayesian integration of a comprehensive, heterogeneous compendium comprising 38,088 genome-scale experiments. The distillation of this knowledge into immunological networks of functional relationships between molecular entities (ImmuNet), and tools to mine this resource, are accessible to the public at http://immunet.princeton.edu. The predictive capacity of ImmuNet, established by rigorous statistical validation, is easily accessed by experimentalists to generate data-driven hypotheses. We demonstrate the power of this approach through the identification of unique host virus interaction responses, and we show how ImmuNet complements genetic studies by predicting disease-associated genes. ImmuNet should be widely beneficial for investigating the mechanisms of the human immune system and immunological diseases. PMID- 26362268 TI - Inhibition of 13-cis retinoic acid-induced gene expression of reactive-resistance genes by thalidomide in glioblastoma tumours in vivo. AB - The cell differentiation potential of 13-cis retinoic acid (RA) has not succeeded in the clinical treatment of glioblastoma (GBM) so far. However, RA may also induce the expression of resistance genes such as HOXB7 which can be suppressed by Thalidomide (THAL). Therefore, we tested if combined treatment with RA+THAL may inhibit growth of glioblastoma in vivo. Treatment with RA+THAL but not RA or THAL alone significantly inhibited tumour growth. The synergistic effect of RA and THAL was corroborated by the effect on proliferation of glioblastoma cell lines in vitro. HOXB7 was not upregulated but microarray analysis validated by real-time PCR identified four potential resistance genes (IL-8, HILDPA, IGFBPA, and ANGPTL4) whose upregulation by RA was suppressed by THAL. Furthermore, genes coding for small nucleolar RNAs (snoRNA) were identified as a target for RA for the first time, and their upregulation was maintained after combined treatment. Pathway analysis showed upregulation of the Ribosome pathway and downregulation of pathways associated with proliferation and inflammation. In conclusion, combined treatment with RA + THAL delayed growth of GBM xenografts and suppressed putative resistance genes associated with hypoxia and angiogenesis. This encourages further pre-clinical and clinical studies of this drug combination in GBM. PMID- 26362270 TI - Genome-wide Association Study (GWAS) of mesocotyl elongation based on re sequencing approach in rice. AB - BACKGROUND: Mechanized dry seeded rice can save both labour and water resources. Rice seedling establishment is sensitive to sowing depth while mesocotyl elongation facilitates the emergence of deeply sown seeds. RESULTS: A set of 270 rice accessions, including 170 from the mini-core collection of Chinese rice germplasm (C Collection) and 100 varieties used in a breeding program for drought resistance (D Collection), was screened for mesocotyl lengths of seedlings grown in water (MLw) in darkness and in 5 cm sand culture (MLs). Twenty six accessions (10.53 %) have MLw longer than 1.0 cm. Eleven accessions had the highest mesocotyl lengths, i.e. 1.4 - 5.05 cm of MLw and 3.0 - 6.4 cm in 10 cm sand culture, including 7 upland landraces or varieties. The genotypic data of 1,019,883 SNPs were developed by re-sequencing of those accessions. A whole genome SNP array (Rice SNP50) was used to genotype 24 accessions as a validation panel, giving 98.41 % of consistent SNPs with the re-sequencing data in average. GWAS based on compressed mixed linear model was conducted using GAPIT. Based on a threshold of -log(P) >=8.0, 13 loci were associated to MLw on rice chromosome 1, 3, 4, 5, 6 and 9, respectively. Three associated loci, on chromosome 3, 6, and 10, were detected for MLs. A set of 99 associated SNPs for MLw, based on a compromised threshold (-log(P) >=7.0), located in intergenic regions or different positions of 36 annotated genes, including one cullin and one growth regulating factor gene. CONCLUSIONS: Higher proportion and extension of elongated mesocotyls were observed in the mini-core collection of rice germplasm and upland rice landraces or varieties, possibly causing the correlation between mesocotyl elongation and drought resistance. GWAS found 13 loci for mesocotyl length measured in dark germination that confirmed the previously reported co-location of two QTLs across populations and experiments. Associated SNPs hit 36 annotated genes including function-matching candidates like cullin and GRF. The germplasm with elongated mesocotyl, especially upland landraces or varieties, and the associated SNPs could be useful in further studies and breeding of mechanized dry seeded rice. PMID- 26362269 TI - IL-1beta produced by aggressive breast cancer cells is one of the factors that dictate their interactions with mesenchymal stem cells through chemokine production. AB - The aim of this work was to understand whether the nature of breast cancer cells could modify the nature of the dialog of mesenchymal stem cells (MSCs) with cancer cells. By treating MSCs with the conditioned medium of metastatic Estrogen receptor (ER)-negative MDA-MB-231, or non-metastatic ER-positive MCF-7 breast cancer cells, we observed that a number of chemokines were produced at higher levels by MSCs treated with MDA-MB-231 conditioned medium (CM). MDA-MB-231 cells were able to induce NF-kappaB signaling in MSC cells. This was shown by the use of a NF-kB chemical inhibitor or an IkappaB dominant negative mutant, nuclear translocation of p65 and induction of NF-kappaB signature. Our results suggest that MDA-MB-231 cells exert their effects on MSCs through the secretion of IL 1beta, that activates MSCs and induces the same chemokines as the MDA-MB-231CM. In addition, inhibition of IL-1beta secretion in the MDA-MB-231 cells reduces the induced production of a panel of chemokines by MSCs, as well the motility of MDA MB-231 cells. Our data suggest that aggressive breast cancer cells secrete IL 1beta, which increases the production of chemokines by MSCs. PMID- 26362271 TI - Excessive watering eyes in gastric cancer patients receiving S-1 chemotherapy. AB - BACKGROUND: Watering eyes is a common late adverse event associated with S-1 chemotherapy; however, the frequency and predictive factors are not known. METHODS: This study included 304 consecutive gastric cancer patients treated with adjuvant S-1 monotherapy for 1 year at Shizuoka Cancer Center. We retrospectively evaluated the frequency of watering eyes, and explored other nonhematological adverse events during the first course of S-1 monotherapy which could become predictive factors for watering eyes. RESULTS: The severest grade of watering eyes during S-1 monotherapy was grade 2 in 41 patients (13.5 %) and grade 3 in 36 patients (11.8 %). The median time to onset of grade 2 and grade 3 watering eyes was 82 days (range 6-344 days) and 249 days (range 84-653 days), respectively, and the median cumulative S-1 dose at the onset of grade 2 and grade 3 watering eyes was 4174 mg/m(2) (range 491-16,095 mg/m(2)) and 10,243 mg/m(2) (range 4943 16,341 mg/m(2)), respectively. Multivariate analysis showed that anorexia (odds ratio 2.37, P = 0.008), oral mucositis (odds ratio 3.86, P = 0.0003), skin hyperpigmentation (odds ratio 3.84, P = 0.0001), and rash (odds ratio 3.76, P = 0.01) observed during the first course were significantly associated with watering eyes. CONCLUSION: The risk of watering eyes was higher in patients who also had anorexia, oral mucositis, skin hyperpigmentation, or rash during first course of S-1 monotherapy than in those without them. PMID- 26362272 TI - Retrospective assessment of patterns of recurrence relative to radiotherapy volumes for adjuvant conformal chemoradiotherapy in gastric cancer. AB - BACKGROUND: Since the Intergroup 0116 study was published in 2000, adjuvant postoperative chemoradiotherapy using CT-planned and 3D conformal/intensity modulated radiotherapy has been offered routinely to fit patients with resected gastric cancer at Princess Margaret Hospital .The objective of this study was to analyze patterns of disease recurrence with respect to the radiotherapy volumes. METHODS: For the date and site (local, locoregional, or distant) of the first recurrence, medical records were reviewed for all patients treated at Princess Margaret Hospital with adjuvant chemoradiotherapy for resected gastric adenocarcinoma (January 1, 2000 to November 30, 2009). Patients whose recurrences were limited to local and/or regional sites were selected for further analysis. Available diagnostic imaging of the recurrence site was registered to the original planning radiotherapy dataset for contouring. If necessary to respect changes in anatomy, the contour was translocated on the basis of anatomic descriptors. The center of mass for each recurrence was identified as a point and its location was categorized according to the isodose encompassing it; in field (90 % or more), marginal (50-89 %), or out of field (less than 50 %). RESULTS: Of all 197 patients, 14 (7 %) had isolated locoregional failure, constituting 20 % of all 71 patients with a recurrence. Successful fusions were feasible in five cases. Of these recurrences, four were in field and one was marginal. In a further four cases, visual inspection was used, showing one in-field recurrence, one marginal recurrence, and two out-of-field recurrences. In five patients, either a useable original dataset or diagnostic imaging of the recurrence was not available. CONCLUSIONS: The rates of isolated local/locoregional tumor recurrence in this study were low. Of the small number of recurrences available for analysis, most (five of nine) were in field. Further studies involving a larger cohort of patients might allow a more meaningful analysis of trends in the recurrence site with evolving radiotherapy techniques. PMID- 26362274 TI - Fondaparinux for Management of Heparin-induced Thrombocytopenia after Cardiovascular Intervention: A Systematic Review. AB - OBJECTIVES: The efficacy and safety of fondaparinux, an emerging therapeutic option for heparin-induced thrombocytopenia (HIT), remain unclear in cardiac surgery patients with HIT. METHODS: Using several search criteria, we reviewed all cases of fondaparinux use in patients who developed HIT after any cardiovascular intervention and were indexed in MEDLINE by August 2014. Based on pre-specified criteria, cases were divided into confirmed HIT, probable HIT and possible HIT. The outcome of fondaparinux use in each group was compared using Chi-square test. RESULTS: Of 43 total cases, 22 had confirmed HIT and 21 had possible HIT. Valve replacement or repair (39%) and heart transplant or ventricular assist device placement (21%) were the most common preceding cardiovascular interventions. Creatinine clearance <30 ml was present in 27% and 52% of confirmed and possible HIT respectively. Overall the risk of new thrombosis and bleeding with fondaparinux were 4.6% and 7% respectively, without any differences in the two subgroups. The majority (86%) of cases improved clinically; of the remainder patients, similar percentage of cases with possible HIT and confirmed HIT died (24% vs. 5%; p= 0.102). None of the deaths were attributed to HIT or complications of bleeding. CONCLUSION: Within the limitations of this study, the risk of thrombosis and bleeding with fondaparinux use in cardiac surgery patients with HIT are low and largely comparable to outcomes reported in literature with other agents. PMID- 26362275 TI - Fibrinolytic Actinokinase--A Short Review. AB - The prevalence of cardiovascular disease is one of the major causes of overall mortality. It kills almost 18-19 million individuals annually. There are a number of synthetic drug departures but the major effects are hemorrhagic impact, immunogenicity, and high price, due to restricted applications. Actinomycetes are the most economically and biotechnologically valuable prokaryotes. They are known to be responsible for the production and successful exploitation as a source of secondary metabolites, and are found to be abundant and active in marine sediments. Natural thrombolytic drugs are increasingly reported as safer, more fascinating and less costly. Actinokinase is a serine protease which cleaves alpha-chain, beta-chains and gamma-chains of fibrinogen. Hence, such mechanistic property makes actinokinase an interesting feature. These microbial fibrinolytic proteases are used for therapeutic approach of medical interest and have biotechnological applications to treat cardiovascular diseases. PMID- 26362273 TI - Report on ISCTM Consensus Meeting on Clinical Assessment of Response to Treatment of Cognitive Impairment in Schizophrenia. AB - If treatments for cognitive impairment are to be utilized successfully, clinicians must be able to determine whether they are effective and which patients should receive them. In order to develop consensus on these issues, the International Society for CNS Clinical Trials and Methodology (ISCTM) held a meeting of experts on March 20, 2014, in Washington, DC. Consensus was reached on several important issues. Cognitive impairment and functional disability were viewed as equally important treatment targets. The group supported the notion that sufficient data are not available to exclude patients from available treatments on the basis of age, severity of cognitive impairment, severity of positive symptoms, or the potential to benefit functionally from treatment. The group reached consensus that cognitive remediation is likely to provide substantial benefits in combination with procognitive medications, although a substantial minority believed that medications can be administered without nonpharmacological therapy. There was little consensus on the best methods for assessing cognitive change in clinical practice. Some participants supported the view that performance-based measures are essential for measurement of cognitive change; others pointed to their cost and time requirements as evidence of impracticality. Interview-based measures of cognitive and functional change were viewed as more practical, but lacking validity without informant involvement or frequent contact from clinicians. The lack of consensus on assessment methods was viewed as attributable to differences in experience and education among key stakeholders and significant gaps in available empirical data. Research on the reliability, validity, sensitivity, and practicality of competing methods will facilitate consensus. PMID- 26362276 TI - Prolylcarboxypeptidase gene expression in the heart and kidney: Effects of obesity and diabetes. AB - Prolylcarboxypeptidase (PRCP) regulates plasma prekallikrein/high molecular weight kininogen/bradykinin axis. It also modulates angiotensin II (Ang II), angiotensin III (Ang III), and alpha-melanocyte stimulating hormone (alpha-MSH) physiological effects. Study suggests that increased plasma PRCP level is associated with cardiovascular risk factors, such as atherosclerosis, inflammation, and diabetes. Since expression pattern of PRCP in Zucker diabetic fatty (ZDF) rat vascular tissue remain unproved, we aimed to study its expression in the heart and kidney. The purpose of the present study was also to obtain systemic information of inflammation status with regard to PRCP expression and function in a high-fat diet (HFD)- fed ZDF rats. The ZDF rats were divided into 2 groups, which were fed a high-fat diet for 16 weeks or 32 weeks. Differential expression and pathological significance of PRCP expression during the consecutive stages of renal disease development were identified. After 16 weeks, ZDF rats exhibited early transiently altered PRCP expression in the heart and kidneys. After 32 weeks, ZDF rats showed continuously altered expression in PRCP and inflammatory markers, which was linked to severe hyperglycemia and nephropathy. Altered expression of PRCP associated with inflammatory mediators was illustrated to be functionally relevant. In further support of an important role of PRCP, we found PRCP protein to be highly elevated in rat plasma and in human plasma and the anti-diabetic agents reversed it. These findings indicate that impairment of tissues within the cardiovascular system influences PRCP expression and suggest that pathogenic mechanisms of deregulated PRCP expression warrant further investigation. PMID- 26362277 TI - Atrial fibrillation in the elderly. AB - The prevalence of atrial fibrillation (AF) increases with age and two-thirds of patients with AF aged over 75 years. In addition, co-morbidities are frequent in the elderly and worsen the prognosis. There are poorer quality of life, increased number of hospitalizations and cardiovascular events. The annual death rate was 8% in patients older than 75 years, and higher among women. There is a significant association between AF and cognitive disorders. Despite highest stroke risk, elderly have been paradoxically less likely to receive oral anticoagulation. This review summarizes available data on the epidemiology, risk factors, and scores of bleeding and systemic embolism, evolution and the approach of elderly patients with AF. PMID- 26362278 TI - Design, Synthesis and Evaluation of Antiplatelet Aggregation Inhibitory Activities of the Analogs of Picotamide. AB - A new class of 4-ethoxyisophthalamides is reported, based on the novel approach of linking the 4-ethoxy to Picotamide. Picotamide, as a combined inhibitor of Thromboxane A2 synthase and receptor, is synthesized in 1985 and attracted the attention of researchers. To improve our knowledge of the structure-activity relationship (SAR) and to obtain new anti-platelet drugs, total 24 unreported compounds of 4-ethoxyisophthalamides were designed and synthesized and were devised taking example by structural features of Picotamide and 4-methoxy-N1,N3 diphenylisophthalamide. The structures of target compounds were identified by MS, 1H-NMR and IR and the in vitro anti-platelet aggregation activities were assessed by Born test. The in vitro results revealed that thirteen derivatives (2b, 2g, 2u, 2q, 2f, 2a, 2r, 2j, 2i, 2v, 2h, 2s, 2d) showed platelet aggregation inhibitory activities induced by 5.0 mM ADP with IC50 values ranging over 0.35 uM 1.12 uM and the pre-six compounds had superior anti-platelet aggregation activities than the reference drug Picotamide, while 2b was the best. These consequences suggested that this novel series may have potential as structural templates for the design and subsequent development of new platelet anti aggregatory drugs. PMID- 26362279 TI - Suspected pharmacokinetic interaction between raltegravir and the 3D regimen of ombitasvir, dasabuvir and paritaprevir/ritonavir in an HIV-HCV liver transplant recipient. PMID- 26362280 TI - Solution structure of an avirulence protein, AVR-Pia, from Magnaporthe oryzae. PMID- 26362281 TI - Computational analysis of amoeboid swimming at low Reynolds number. AB - Recent experimental work has shown that eukaryotic cells can swim in a fluid as well as crawl on a substrate. We investigate the swimming behavior of Dictyostelium discoideum amoebae who swim by initiating traveling protrusions at the front that propagate rearward. In our model we prescribe the velocity at the surface of the swimming cell, and use techniques of complex analysis to develop 2D models that enable us to study the fluid-cell interaction. Shapes that approximate the protrusions used by Dictyostelium discoideum can be generated via the Schwarz-Christoffel transformation, and the boundary-value problem that results for swimmers in the Stokes flow regime is then reduced to an integral equation on the boundary of the unit disk. We analyze the swimming characteristics of several varieties of swimming Dictyostelium discoideum amoebae, and discuss how the slenderness of the cell body and the shapes of the protrusion effect the swimming of these cells. The results may provide guidance in designing low Reynolds number swimming models. PMID- 26362282 TI - Predicting a Response to Antibiotics in Patients with the Irritable Bowel Syndrome. AB - BACKGROUND: Antibiotics for presumed small intestinal bacterial overgrowth have been shown to improve irritable bowel syndrome symptoms in at least 40% of subjects. A lactulose breath test for small intestinal bacterial overgrowth has been used to select patients who will respond. However, its predictive value, using the classic definition of a positive lactulose breath test, has been disappointing. AIMS: We conducted a retrospective evaluation to study characteristics of the lactulose breath test that may be predictive of a response to antibiotics in patients with the irritable bowel syndrome. METHODS: A clinical practice database was interrogated for consecutive patients who had a lactulose breath test for irritable bowel syndrome symptoms and a subsequent antibiotic course. Hydrogen + methane levels with carbon dioxide correction were plotted against time. Various profiles of the breath test curves were catalogued and compared with respect to their predictive value for symptom response to antibiotics. RESULTS: Lactulose breath test graphs of 561 patients of all irritable bowel syndrome subtypes were grouped into categories based on their hydrogen + methane levels with respect to time. Of subjects whose hydrogen + methane rise was <20 ppm throughout the test (group 1; N = 95), 94.7% improved after antibiotics (95% CI 90.1-99.3). Of those with a rise <20 ppm within the first 90 min but a rise >50 ppm thereafter (group 3; N = 53), 47.2% improved (95% CI 33.7-60.6). The difference between groups 1 and 3 was statistically significant P < 0.001. CONCLUSION: A lactulose breath test appears to be useful in predicting response to antibiotics in patients with the irritable bowel syndrome. A hydrogen + methane rise <20 ppm throughout the duration of the test is most predictive. This observation contradicts the classic definition of a positive lactulose breath test. PMID- 26362284 TI - Cognitive decline in Parkinson disease: How steep and crowded is the slope? PMID- 26362283 TI - Higher neutrophil counts before thrombolysis for cerebral ischemia predict worse outcomes. AB - OBJECTIVE: To determine whether higher neutrophil counts before IV recombinant tissue plasminogen activator (rtPA) administration in ischemic stroke (IS) patients are associated with symptomatic intracerebral hemorrhages (sICH) and worse outcomes at 3 months. METHODS: Blood samples for leukocyte, neutrophil, and lymphocyte counts were drawn before IV rtPA administration in IS patients included in the cohorts of Lille and Helsinki. The primary endpoint was sICH (European Cooperative Acute Stroke-II definition). Secondary endpoints were death and excellent (modified Rankin Scale [mRS] score 0-1 or equal to prestroke mRS) and good (mRS score 0-2 or equal to prestroke mRS) outcomes at 3 months. RESULTS: We included 846 patients (median age 71 years; 50.8% men). The neutrophil count and neutrophil to lymphocyte ratio (NLR) were independently associated with the 4 endpoints: sICH (adjusted odds ratio [adjOR] for an increase of 1,000 neutrophils = 1.21 and adjOR 1.11, respectively), death (adjOR 1.16 and adjOR 1.08), and excellent (adjOR 0.87 and adjOR 0.85) and good (adjOR 0.86 and adjOR 0.91) outcomes. The total leukocyte count was not associated with any of the 4 endpoints. The best discriminating factor for sICH was NLR >=4.80 (sensitivity 66.7%, specificity 71.3%, likelihood ratio 2.32). Patients with NLR >=4.80 had a 3.71-fold increased risk for sICH (95% confidence interval adjOR: 1.97-6.98) compared to patients with NLR <4.80. CONCLUSIONS: Higher neutrophil counts and NLR are independently associated with sICH and worse outcome at 3 months. The identification of mediators of this effect could provide new targets for neuroprotection in patients treated by rtPA. PMID- 26362285 TI - Longitudinal study of normal cognition in Parkinson disease. AB - OBJECTIVE: To report the rates and predictors of progression from normal cognition to either mild cognitive impairment (MCI) or dementia using standardized neuropsychological methods. METHODS: A prospective cohort of patients diagnosed with Parkinson disease (PD) and baseline normal cognition was assessed for cognitive decline, performance, and function for a minimum of 2 years, and up to 6. A panel of movement disorders experts classified patients as having normal cognition, MCI, or dementia, with 55/68 (80.9%) of eligible patients seen at year 6. Kaplan-Meier curves and Cox proportional hazard models were used to examine cognitive decline and its predictors. RESULTS: We enrolled 141 patients, who averaged 68.8 years of age, 63% men, who had PD on average for 5 years. The cumulative incidence of cognitive impairment was 8.5% at year 1, increasing to 47.4% by year 6. All incident MCI cases had progressed to dementia by year 5. In a multivariate analysis, predictors of future decline were male sex (p = 0.02), higher Unified Parkinson's Disease Rating Scale motor score (p <= 0.001), and worse global cognitive score (p < 0.001). CONCLUSIONS: Approximately half of patients with PD with normal cognition at baseline develop cognitive impairment within 6 years and all new MCI cases progress to dementia within 5 years. Our results show that the transition from normal cognition to cognitive impairment, including dementia, occurs frequently and quickly. Certain clinical and cognitive variables may be useful in predicting progression to cognitive impairment in PD. PMID- 26362287 TI - Charcot-Marie-Tooth disease: New insights from skin biopsy. AB - OBJECTIVE: To evaluate, by skin biopsy, dermal nerve fibers in 31 patients with 3 common Charcot-Marie-Tooth (CMT) genotypes (CMT1A, late-onset CMT1B, and CMTX1), and rarer forms of CMT caused by mutations in RAB7 (CMT2B), TRPV4 (CMT2C), and GDAP1 (AR-CMT2K) genes. METHODS: We investigated axonal loss by quantifying Meissner corpuscles and intrapapillary myelinated endings and evaluated morphometric changes in myelinated dermal nerve fibers by measuring fiber caliber, internodal, and nodal gap length. RESULTS: The density of both Meissner corpuscles and intrapapillary myelinated endings was reduced in skin samples from patients with CMT1A and all the other CMT genotypes. Nodal gaps were larger in all the CMT genotypes though widening was greater in CMT1A. Perhaps an altered communication between axons and glia may be a common feature for multiple forms of CMT. Internodal lengths were shorter in all the CMT genotypes, and patients with CMT1A had the shortest internodes of all our patients. The uniformly shortened internodes in all the CMT genotypes suggest that mutations in both myelin and axon genes may developmentally impede internode formation. The extent of internodal shortening and nodal gap widening are likely both important in determining nerve conduction velocities in CMT. CONCLUSIONS: This study extends the information gained from skin biopsies on morphologic abnormalities in various forms of CMT and provides insights into potential pathomechanisms of axonal and demyelinating CMT. PMID- 26362288 TI - Cerebral hemorrhage following thrombolytic therapy for stroke: Are neutrophils really neutral? PMID- 26362286 TI - A randomized, double-blind, placebo-controlled trial of resveratrol for Alzheimer disease. AB - OBJECTIVE: A randomized, placebo-controlled, double-blind, multicenter 52-week phase 2 trial of resveratrol in individuals with mild to moderate Alzheimer disease (AD) examined its safety and tolerability and effects on biomarker (plasma Abeta40 and Abeta42, CSF Abeta40, Abeta42, tau, and phospho-tau 181) and volumetric MRI outcomes (primary outcomes) and clinical outcomes (secondary outcomes). METHODS: Participants (n = 119) were randomized to placebo or resveratrol 500 mg orally once daily (with dose escalation by 500-mg increments every 13 weeks, ending with 1,000 mg twice daily). Brain MRI and CSF collection were performed at baseline and after completion of treatment. Detailed pharmacokinetics were performed on a subset (n = 15) at baseline and weeks 13, 26, 39, and 52. RESULTS: Resveratrol and its major metabolites were measurable in plasma and CSF. The most common adverse events were nausea, diarrhea, and weight loss. CSF Abeta40 and plasma Abeta40 levels declined more in the placebo group than the resveratrol-treated group, resulting in a significant difference at week 52. Brain volume loss was increased by resveratrol treatment compared to placebo. CONCLUSIONS: Resveratrol was safe and well-tolerated. Resveratrol and its major metabolites penetrated the blood-brain barrier to have CNS effects. Further studies are required to interpret the biomarker changes associated with resveratrol treatment. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with AD resveratrol is safe, well-tolerated, and alters some AD biomarker trajectories. The study is rated Class II because more than 2 primary outcomes were designated. PMID- 26362290 TI - Global Antimicrobial Stewardship: Challenges and Successes from Frontline Stewards. PMID- 26362289 TI - Accelerated rates of protein evolution in barley grain and pistil biased genes might be legacy of domestication. AB - Traits related to grain and reproductive organs in grass crops have been under continuous directional selection during domestication. Barley is one of the oldest domesticated crops in human history. Thus genes associated with the grain and reproductive organs in barley may show evidence of dramatic evolutionary change. To understand how artificial selection contributes to protein evolution of biased genes in different barley organs, we used Digital Gene Expression analysis of six barley organs (grain, pistil, anther, leaf, stem and root) to identify genes with biased expression in specific organs. Pairwise comparisons of orthologs between barley and Brachypodium distachyon, as well as between highland and lowland barley cultivars mutually indicated that grain and pistil biased genes show relatively higher protein evolutionary rates compared with the median of all orthologs and other organ biased genes. Lineage-specific protein evolutionary rates estimation showed similar patterns with elevated protein evolution in barley grain and pistil biased genes, yet protein sequences generally evolve much faster in the lowland barley cultivar. Further functional annotations revealed that some of these grain and pistil biased genes with rapid protein evolution are related to nutrient biosynthesis and cell cycle/division. Our analyses provide insights into how domestication differentially shaped the evolution of genes specific to different organs of a crop species, and implications for future functional studies of domestication genes. PMID- 26362291 TI - Antimicrobial Stewardship with Pharmacist Intervention Improves Timeliness of Antimicrobials Across Thirty-three Hospitals in South Africa. AB - INTRODUCTION: Ensuring timely administration of antimicrobials is critical in the management of patients with infections. Mortality increases by 7.6% for every hour of delay in the administration of antimicrobial therapy in patients with sepsis. The time elapsed from the written antibiotic order to actual intravenous administration or 'hang-time' can often be several hours due to logistics within the hospital. Our purpose is to evaluate the change in compliance with administering antimicrobials within an hour of prescription after implementation of a national antibiotic stewardship pharmacist-driven hang-time process improvement protocol. METHODS: This was a prospective multicenter study in 33 South African hospitals from 1 July 2013-30 August 2014. Two pilot sites established the mechanism for noninfectious disease pharmacists to make interventions and document hang-time data. Following this, a hang-time compliance assessment was initiated using the tools of healthcare improvement spread methodology. This consisted of five stages and an implementation toolkit was developed. The pharmacist study coordinator was responsible for implementation, the development of an implementation toolkit and real-time coordination of data with monthly feedback to all sites. RESULTS: A total of 32,985 patients who received intravenous antibiotics were assessed for hang-time compliance with first doses of new antibiotic orders. Over the 60-week period, 21,069 patients received antibiotics within an hour following prescription and were assessed as hang-time compliant. The change in improvement of hang-time compliance following implementation of a pharmacist-driven hang-time process improvement protocol was 41.2% pre-intervention week 1 (164/398) to 78.4% post-intervention week 60 (480/612; P < 0.0001). Pharmacists reviewed and evaluated twice as many patients during the final 4 weeks (1680) compared to the first 4 weeks (834; P < 0.0001). CONCLUSION: Noninfectious disease pharmacists can significantly improve the timely administration of antimicrobials and contribute to low-hanging-fruit antimicrobial stewardship initiatives within a hospital system in a resource limited country. PMID- 26362292 TI - Considerations About Antimicrobial Stewardship in Settings with Epidemic Extended Spectrum beta-Lactamase-Producing or Carbapenem-Resistant Enterobacteriaceae. AB - Infections caused by gram-negative bacteria (GNB) resistant to multiple classes of antibiotics are increasing in many hospitals. Extended-spectrum beta-lactamase (ESBL)-producing and carbapenem-resistant Enterobacteriaceae in particular are now endemic in many parts of the world and represent a serious public health threat. In this era, antimicrobial stewardship programs are essential as targeted and responsible use of antibiotics improves patient outcomes and hopefully limits the selective pressure that drives the further emergence of resistance. However, some stewardship strategies aimed at promoting carbapenem-sparing regimens remain controversial and are difficult to implement when resistance rates to non carbapenem antibiotics are increasing. Coordinated efforts between stewardship programs and infection control are essential for reversing conditions that favor the emergence and dissemination of multidrug-resistant GNB within the hospital and identifying extra-institutional "feeder reservoirs" of resistant strains such as long-term care facilities, where colonization is common despite limited numbers of serious infections. In settings where ESBL resistance is endemic, the cost-effectiveness of expanded infection control efforts and antimicrobial stewardship is still unknown. Once a patient has been colonized, selective oral or digestive decontamination may be considered, but evidence supporting its effectiveness is limited in patients who are already colonized or in centers with high rates of resistance. Moreover, temporary success at decolonization may be associated with a higher risk of relapse with strains that are resistant to the decolonizing antibiotics. PMID- 26362294 TI - Antimicrobial Stewardship in Australian Hospitals and Other Settings. AB - Australia's model of antimicrobial stewardship (AMS) has evolved significantly over recent years, from a long-standing national approach of antimicrobial prescribing guidelines and antimicrobial prescribing restrictions to recent advances including the first National Antimicrobial Resistance Strategy and incorporating mandatory AMS as part of hospital accreditation standards. AMS programs are most commonly found in the hospital setting. Various models are used throughout the country based on the local context and resources available. Programs implemented at Alfred Health and the Royal Brisbane and Women's Hospital represent two successful models in tertiary referral settings that accommodate a general ward setting as well as specialized areas with a high infection burden. Measurement of outcomes related to AMS activities remains poorly standardized, with process indicators such as antimicrobial utilization forming a large proportion of outcome measurement. Presently there is no requirement for any AMS outcome measurements to be reported externally. Point prevalence surveys of appropriateness of prescribing and compliance with prescribing guidelines are widely used at a national level. Despite this, there is still a paucity of published Australian data to support the effect of AMS on patient clinical outcomes. Private hospitals, the community, veterinary medicine and aged care sectors represent an important area for future AMS expansion within Australia. The AMS focus has traditionally been on prescribing restrictions (through the Commonwealth funding agencies); however, recent work has described other areas for improvement and development in both settings. AMS in Australia continues to evolve. The recent development of an Australian strategic plan to link antimicrobial utilization and resistance surveillance with policy represents an important step forward for the future of AMS in Australia. PMID- 26362293 TI - Antimicrobial Stewardship in the Emergency Department. AB - The literature contains robust evidence on the positive impact of antimicrobial stewardship programs (ASP) in the inpatient setting. With national policies shifting toward provisions of quality health care, the impetus to expand ASP services becomes an important strategy for institutions. However data on stewardship initiatives in other settings are less characterized. For organizations with an established ASP team, it is rational to consider expanding these services to the emergency department (ED). The ED serves as an interface between the inpatient and community settings. It is often the first place where patients present for medical care, including for common infections. Challenges inherent to the fast-paced nature of the environment must be recognized for successful ASP implementation in the ED. Based on the current literature, a combination of strategies for initiating ASP services in the ED will be described. Furthermore, common scenarios and management approaches are proposed for respiratory tract, skin and soft tissue, and urinary tract infections. Expansion of ASP services across the health care continuum may improve patient outcomes with a potential associated decrease in health care costs while preventing adverse effects including the development of antibiotic resistance. PMID- 26362295 TI - Antimicrobial Stewardship from Policy to Practice: Experiences from UK Antimicrobial Pharmacists. AB - Antimicrobial stewardship in the UK has evolved dramatically in the last 15 years. Factors driving this include initial central funding for specialist pharmacists and mandatory reductions in healthcare-associated infections (particularly Clostridium difficile infection). More recently, the introduction of national stewardship guidelines, and an increased focus on stewardship as part of the UK five-year antimicrobial resistance strategy, have accelerated and embedded developments. Antimicrobial pharmacists have been instrumental in effecting changes at an organizational and national level. This article describes the evolution of the antimicrobial pharmacist role, its impact, the progress toward the actions listed in the five-year resistance strategy, and novel emerging areas in stewardship in the UK. PMID- 26362296 TI - Impact of Antimicrobial Stewardship Program (ASP) on Outcomes in Patients with Acute Bacterial Skin and Skin Structure Infections (ABSSSIs) in an Acute-Tertiary Care Hospital. AB - INTRODUCTION: Acute bacterial skin and skin structure infections (ABSSSIs) are among the most common infections treated in hospitals, but to date, there has been little information with regards to the implementation of Antimicrobial Stewardship Programs (ASPs) for patients with ABSSSIs. Hence, we aim to evaluate the impact of ASPs on the following outcomes in patients with ABSSSIs: duration of therapy and hospital stay, 14-day reinfection, infection-related readmissions and mortality. METHODS: A retrospective review of the ASP database was conducted, focusing on selected outcomes (as above) among all patients in whom the institution's ASP recommended a change in antibiotic regimen-de-escalation of the antibiotic based on culture results; discontinuation of the antibiotic; narrowing of the empirical coverage; and intravenous-to-oral (i.v.-to-p.o.) switch between September 2009 and December 2012. Data were expressed as mean +/- standard deviation for continuous variables, and unpaired Student's t test was performed to determine intergroup differences between mean values. For categorical variables, data were presented as number and percentage and analyzed using the chi (2) test or Fisher's exact test, as appropriate. RESULTS: ASP recommended 407 interventions with an overall acceptance rate of 66.8%. ASP interventions significantly reduced median duration of therapy by 2 [from a median (interquartile range, IQR) of 8 (6-12) days to 6 (4-9) days] and median length of stay by 5 days [from median (IQR) of 12 (5-32) days to 7 (3-18) days]. This led to an estimated total cost avoidance of USD 0.7 million. There were no significant differences in the 14-day reinfection, infection-related readmission and mortality rates between patients whose physicians accepted and those who rejected ASP interventions. CONCLUSION: Interventions recommended by the ASP in Singapore General Hospital were safe and associated with a significant reduction in duration of therapy and hospital stay. The results of our study have affirmed the role of ASP in optimizing the care of patients with ABSSSI. PMID- 26362297 TI - Father Involvement and Young, Rural African American Men's Engagement in Substance Misuse and Multiple Sexual Partnerships. AB - This study was designed to examine the associations of biological father and social father involvement during childhood with African American young men's development and engagement in risk behaviors. With a sample of 505 young men living in the rural South of the United States, a dual mediation model was tested in which retrospective reports of involvement from biological fathers and social fathers were linked to young men's substance misuse and multiple sexual partnerships through men's relational schemas and future expectations. Results from structural equation modeling indicated that levels of involvement from biological fathers and social fathers predicted young men's relational schemas; only biological fathers' involvement predicted future expectations. In turn, future expectations predicted levels of substance misuse, and negative relational schemas predicted multiple sexual partnerships. Biological fathers' involvement evinced significant indirect associations with young men's substance misuse and multiple sexual partnerships through both schemas and expectations; social fathers' involvement exhibited an indirect association with multiple sexual partnerships through relational schemas. Findings highlight the unique influences of biological fathers and social fathers on multiple domains of African American young men's psychosocial development that subsequently render young men more or less likely to engage in risk behaviors. PMID- 26362298 TI - Transcriptional master regulator analysis in breast cancer genetic networks. AB - Gene regulatory networks account for the delicate mechanisms that control gene expression. Under certain circumstances, gene regulatory programs may give rise to amplification cascades. Such transcriptional cascades are events in which activation of key-responsive transcription factors called master regulators trigger a series of gene expression events. The action of transcriptional master regulators is then important for the establishment of certain programs like cell development and differentiation. However, such cascades have also been related with the onset and maintenance of cancer phenotypes. Here we present a systematic implementation of a series of algorithms aimed at the inference of a gene regulatory network and analysis of transcriptional master regulators in the context of primary breast cancer cells. Such studies were performed in a highly curated database of 880 microarray gene expression experiments on biopsy-captured tissue corresponding to primary breast cancer and healthy controls. Biological function and biochemical pathway enrichment analyses were also performed to study the role that the processes controlled - at the transcriptional level - by such master regulators may have in relation to primary breast cancer. We found that transcription factors such as AGTR2, ZNF132, TFDP3 and others are master regulators in this gene regulatory network. Sets of genes controlled by these regulators are involved in processes that are well-known hallmarks of cancer. This kind of analyses may help to understand the most upstream events in the development of phenotypes, in particular, those regarding cancer biology. PMID- 26362299 TI - Core and peripheral connectivity based cluster analysis over PPI network. AB - A number of methods have been proposed in the literature of protein-protein interaction (PPI) network analysis for detection of clusters in the network. Clusters are identified by these methods using various graph theoretic criteria. Most of these methods have been found time consuming due to involvement of preprocessing and post processing tasks. In addition, they do not achieve high precision and recall consistently and simultaneously. Moreover, the existing methods do not employ the idea of core-periphery structural pattern of protein complexes effectively to extract clusters. In this paper, we introduce a clustering method named CPCA based on a recent observation by researchers that a protein complex in a PPI network is arranged as a relatively dense core region and additional proteins weakly connected to the core. CPCA uses two connectivity criterion functions to identify core and peripheral regions of the cluster. To locate initial node of a cluster we introduce a measure called DNQ (Degree based Neighborhood Qualification) index that evaluates tendency of the node to be part of a cluster. CPCA performs well when compared with well-known counterparts. Along with protein complex gold standards, a co-localization dataset has also been used for validation of the results. PMID- 26362300 TI - An Update on Inpatient Hypertension Management. AB - Hypertension is highly prevalent affecting nearly one third of the US adult population. Though generally approached as an outpatient disorder, elevated blood pressure is observed in a majority of hospitalized patients. The spectrum of hypertensive disease ranges from patients with hypertensive emergency including markedly elevated blood pressure and associated end-organ damage to asymptomatic patients with minimally elevated pressures of unclear significance. It is important to note that current evidence-based hypertension guidelines do not specifically address inpatient hypertension. This narrative review focuses primarily on best practices for diagnosing and managing nonemergent hypertension in the inpatient setting. We describe examples of common hypertensive syndromes, provide suggestions for optimal post-acute management, and point to evidence based or consensus guidelines where available. In addition, we describe a practical approach to managing asymptomatic elevated blood pressure observed in the inpatient setting. Finally, arranging effective care transitions to ensure optimal ongoing hypertension management is appropriate in all cases. PMID- 26362302 TI - SGLT2 inhibitors. AB - Diabetes mellitus is a serious health issue and an economic burden, rising in epidemic proportions over the last few decades worldwide. Although several treatment options are available, only half of the global diabetic population achieves the recommended or individualized glycemic targets. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of antidiabetic agents with a novel insulin-independent action. SGLT2 is a transporter found in the proximal renal tubules, responsible for the reabsorption of most of the glucose filtered by the kidney. Inhibition of SGLT2 lowers the blood glucose level by promoting the urinary excretion of excess glucose. Due to their insulin-independent action, SGLT2 inhibitors can be used with any degree of beta-cell dysfunction or insulin resistance, related to a very low risk of hypoglycemia. In addition to improving glycemic control, SGLT2 inhibitors have been associated with a reduction in weight and blood pressure when used as monotherapy or in combination with other antidiabetic agents in patients with type 2 diabetes mellitus (T2DM). Treatment with SGLT2 inhibitors is usually well tolerated; however, they have been associated with an increased incidence of urinary tract and genital infections, although these infections are usually mild and easy to treat. SGLT2 inhibitors are a promising new option in the armamentarium of drugs for patients with T2DM. PMID- 26362303 TI - Snap-lock bags with red band: A study of manufacturing characteristics, thermal and chemical properties. AB - Drug packaging is commonly submitted to the Forensic Chemistry and Physics Laboratory of the Health Sciences Authority, Singapore, for examination. The drugs seized are often packaged in plastic bags. These bags are examined for linkages to provide law enforcement with useful associations between the traffickers and drug abusers. The plastic bags submitted may include snap-lock bags, some with a red band located above the snap-lock closure and some without. Current techniques for examination involve looking at the physical characteristics (dimensions, thickness and polarising patterns) and manufacturing marks of these bags. In cases where manufacturing marks on the main body of the bags are poor or absent, the manufacturing characteristics present on the red band can be examined. A study involving approximately 1000 bags was conducted to better understand the variations in the manufacturing characteristics of the red band. This understanding is crucial in helping to determine associations/eliminations between bags. Two instrumental techniques, namely differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR) were explored to evaluate the effectiveness of examining the chemical composition to discriminate the bags. PMID- 26362301 TI - The Evaluation and Therapeutic Management of Hypertension in the Transplant Patient. AB - Organ transplantation is the therapeutic option of choice in the appropriate patient with end-organ disease. A major comorbidity after the transplant is the development of hypertension which is a risk factor for cardiovascular disease. Cardiovascular disease is the most common cause of death in this population even when there is a functioning graft. It is essential to evaluate post-transplant hypertension not only in the office setting but at home and at night as well. Hence, the use of 24-h ambulatory blood pressure monitoring in both diagnosis and long-term care of this patient population is paramount. Factors involved in uncontrolled hypertension include the donor, recipient, and those specific to the transplant such as immunosuppressive drug exposure. The major offending immunosuppressive agents belong to the calcineurin inhibitor class. The therapy of post-transplant hypertension involves pharmaceutical and non-pharmaceutical interventions that should be tailored to the specific patient and type of transplant. There is clearly a need for more definitive data and quality studies in both the renal and non-renal transplant populations. PMID- 26362304 TI - [Ligament reconstruction in extensor tendon dislocation]. AB - OBJECTIVE: Stabile recentering the extensor tendon over the top of the head of the metacarpal to restore the exact tension and the direction. INDICATIONS: Dislocation of the extensor tendon at the metacarpophalangeal (MP) joint with functional disabilities of the fingers. CONTRAINDICATIONS: Severe osteoarthritis of the MP joint. Accompanying injuries of collateral ligaments. Fibrosis of the MP joint or contractures of the intrinsic muscles. SURGICAL TECHNIQUE: Curved 8 cm skin incision at distal metacarpal, MP joint, and proximal phalanx. A distally pedicled central tendon strip from the extensor digitorum communis (EDC) tendon is removed. Centralization of the tendon by reconstructing the sagittal ligament and the proximal part of the extensor hood. The tendon strip is wrapped around the tendon of the interossous muscle. POSTOPERATIVE MANAGEMENT: Immobilization of the MP joint in 30 degrees flexion with free proximal interphalangeal (PIP) and distal interphalangeal (DIP) joints for 4 weeks. Full fist after 5 weeks. RESULTS: In all 16 patients good or very good results were achieved. There were no recurrences of tendon dislocations, no MP joint contractures, and only a few minor extensor tendon adhesions. PMID- 26362305 TI - A case of acute subdural hematoma due to ruptured aneurysm detected by postmortem angiography. AB - Acute subdural hematoma (ASDH) is mostly caused by head trauma, but intrinsic causes also exist such as aneurysm rupture. We describe here a case involving a man in his 70s who was found lying on the bedroom floor by his family. CT performed at the hospital showed ASDH and a forensic autopsy was requested. Postmortem cerebral angiography showed dilatation of the bifurcation of the middle cerebral artery, which coincided with the dilated part of the Sylvian fissure. Extravasation of contrast medium into the subdural hematoma from this site was suggestive of a ruptured aneurysm. Autopsy revealed a fleshy hematoma (total weight 110 g) in the right subdural space and findings of brain herniation. As indicated on angiography, a ruptured saccular aneurysm was confirmed at the bifurcation of the middle cerebral artery. Obvious injuries to the head or face could not be detected on either external or internal examination, and intrinsic ASDH due to a ruptured middle cerebral artery aneurysm was determined as the cause of death. One of the key points of forensic diagnosis is the strict differentiation between intrinsic and extrinsic onset for conditions leading to death. Although most subdural hematomas (SDH) are caused by extrinsic factors, forensic pathologists should consider the possibility of intrinsic SDH. In addition, postmortem angiography can be useful for identifying vascular lesions in such cases. PMID- 26362306 TI - Possible application of CT morphometry of the calcaneus and talus in forensic anthropological identification. AB - Computed tomography (CT) data provide information for volumetric and radiographic density analysis. The present study investigated the application of virtual CT volumetry of the tarsal bones to estimation of the sex, stature, and body weight using postmortem CT (PMCT) data of forensic autopsy cases. Three-dimensional (3D) images of the bilateral foot bones of intact Japanese subjects after adolescence (age >= 15 years, n = 179, 100 males and 79 females) were reconstructed on an automated CT image analyzer system. Measured parameters were mass volume, mean CT value (HU), and total CT value of the talus and calcaneus. Mean CT values of these bones showed age-dependent decreases in elderly subjects over 60 years of age for both sexes, with significant sex-related differences especially in the elderly. The mass volumes and total CT values of the talus and calcaneus showed significant sex-related differences, and also moderate correlations with body height and weight for bilateral bones in all cases (r = 0.58-0.78, p < 0.0001); however, the correlations of these parameters of the female talus with body weight were insufficient (r = 0.41-0.61, p < 0.0001). These observations indicate the applicability of virtual CT morphometry of the talus and calcaneus using an automated analyzer to estimate the sex and stature in forensic identification; however, greater variations should be considered in body weight estimations of females. PMID- 26362307 TI - Early Respiratory Infections and the Development of Asthma in the First 27 Years of Life. AB - Previous studies have provided contradictory evidence on the role of early childhood respiratory infections in the development of asthma and other allergic diseases during childhood. We investigated early-life respiratory infections as predictors of the development of asthma in a 20-year prospective cohort study (the Espoo Cohort Study, 1991-2011). Information on upper respiratory tract infections (URTIs) and lower respiratory tract infections (LRTIs) was collected with a parent-administered baseline questionnaire covering the preceding 12 months (part 1; n = 2,228), and information on LRTIs leading to hospitalization was obtained from the National Hospital Discharge Registry (part 2; n = 2,568). The incidence of asthma was assessed on the basis of 6-year and 20-year follow-up questionnaires. Adjusted hazard ratios were estimated using Cox proportional hazards models. Both URTIs (adjusted hazard ratio (HR) = 1.64, 95% confidence interval (CI): 1.22, 2.19) and LRTIs (adjusted HR = 2.11, 95% CI: 1.48, 3.00) in early childhood were strong predictors of asthma incidence up to young adulthood (ages 20-27 years). A declining age trend was present for both URTIs (P-trend < 0.01) and LRTIs (P-trend < 0.001). In part 2 of our analysis, a significant risk of asthma was found in relation to LRTIs requiring hospitalization (adjusted HR = 1.93, 95% CI: 1.10, 3.38). The results provide new evidence that respiratory tract infections in early life predict the development of asthma through childhood to young adulthood. PMID- 26362308 TI - Stress-Induced Depressive Behaviors Require a Functional NLRP3 Inflammasome. AB - Depression is a major public health concern in modern society, yet little is known about the molecular link between this condition and neuroinflammation. The inflammasome complex was recently shown to be implicated in depression. The present study shows the implication of NLRP3 inflammasome in animal model of stress-induced depression. Accordingly, we show here that in the absence of a NLRP3 inflammasome, prolonged stress does not provoke depressive behaviors or microglial activation in mice or dampen hippocampal neurogenesis. Indeed, NLRP3 deletion or inhibition of microglial activation impairs the stress-induced alterations associated with depression. According to these findings in animal model, the inflammasome could be a target for new therapeutic interventions to prevent depression in patients. PMID- 26362309 TI - Neprilysin Confers Genetic Susceptibility to Alzheimer's Disease in Han Chinese. AB - Alzheimer's disease (AD) is a progressive neurodegenerative disease, with increasing incidence all over the world. Amyloid-beta (Abeta) was considered to be the original cause to AD, and many reported pathogenic or risk genes for AD were located in the Abeta generation and degradation pathways. Neprilysin (NEP), insulin-degrading enzyme (IDE), and matrix metalloprotease-9 (MMP-9) are the most important Abeta-degrading proteases. Accumulating genetic evidence suggested that single nucleotide polymorphisms (SNPs) of these genes confer susceptibility to AD in Caucasian populations. In this study, we screened eight SNPs within these three Abeta-degrading protease genes in 1475 individuals of two independent Han Chinese case-control cohorts. SNP rs1816558 of NEP was found to be significantly associated with AD after adjustment for epsilon4 allele of the apolipoprotein E gene (APOEepsilon4) and the Bonferroni correction. The remaining variants were not associated with risk of AD in Han Chinese sample set. Further data mining revealed that messenger RNA (mRNA) level of NEP substantially increased during the development of AD and was positively correlated with APP expression. The combined results indicated that NEP confers genetic susceptibility to AD in Han Chinese populations. PMID- 26362310 TI - Chemotherapy induces Notch1-dependent MRP1 up-regulation, inhibition of which sensitizes breast cancer cells to chemotherapy. AB - BACKGROUND: Multi-drug Resistance associated Protein-1 (MRP1) can export chemotherapeutics from cancer cells and is implicated in chemoresistance, particularly as is it known to be up-regulated by chemotherapeutics. Our aims in this study were to determine whether activation of Notch signalling is responsible for chemotherapy-induced MRP1 expression Notch in breast cancers, and whether this pathway can be manipulated with an inhibitor of Notch activity. METHODS: MRP1 and Notch1 were investigated in 29 patients treated with neoadjuvant chemotherapy (NAC) for breast cancer, using immunohistochemistry on matched biopsy (pre-NAC) and surgical samples (post-NAC). Breast epithelial cell cultures (T47D, HB2) were treated with doxorubicin in the presence and absence of functional Notch1, and qPCR, siRNA, Western blots, ELISAs and flow-cytometry were used to establish interactions. RESULTS: In clinical samples, Notch1 was activated by neoadjuvant chemotherapy (Wilcoxon signed-rank p < 0.0001) and this correlated with induction of MRP1 expression (rho = 0.6 p = 0.0008). In breast cell lines, doxorubicin induced MRP1 expression and function (non-linear regression p < 0.004). In the breast cancer line T47D, doxorubicin activated Notch1 and, critically, inhibition of Notch1 activation with the gamma-secretase inhibitor DAPT abolished the doxorubicin-induced increase in MRP1 expression and function (t-test p < 0.05), resulting in enhanced cellular retention of doxorubicin and increased doxorubicin-induced apoptosis (t-test p = 0.0002). In HB2 cells, an immortal but non-cancer derived breast cell line, Notch1 independent MRP1 induction was noted and DAPT did not enhance doxorubicin-induced apoptosis. CONCLUSIONS: Notch inhibitors may have potential in sensitizing breast cancer cells to chemotherapeutics and therefore in tackling chemoresistance. PMID- 26362313 TI - Deficiencies in services for acute upper gastrointestinal bleeding. PMID- 26362312 TI - DDR2 facilitates hepatocellular carcinoma invasion and metastasis via activating ERK signaling and stabilizing SNAIL1. AB - BACKGROUND: Several studies have found that DDR2 is up-regulated in many tumor types and facilitates tumor progression. However, the role of DDR2 in hepatocellular carcinoma (HCC) progression and its downstream signaling pathways remain unclear. METHODS: DDR2 expression was assessed in several cell lines and 112 pairs of HCC and matched adjacent noncancerous liver tissues. Clinical significance of DDR2 in HCC was analyzed. Phosphorylated DDR2 (p-DDR2) expression was detected by immunoblotting to evaluate its correlation with DDR2. The effect of DDR2 on HCC cell migration and invasion were examined. Cycloheximide chase experiments were performed to detect the half-life of SNAIL1. Moreover, DDR2 expression was detected by immunohistochemistry to evaluate its correlation with SNAIL1. The regulatory effect of DDR2 on ERK signaling, SNAIL1, EMT, MT1-MMP and MMP2 was confirmed by immunoblotting. The effect of type I collagen on DDR2/ERK2/SNAIL1 signaling was assessed. RESULTS: DDR2 was more highly expressed in HCC than in non-HCC tissues. DDR2 overexpression was correlated with clinicopathological features of poor prognosis. Clinical analysis revealed that DDR2 is an independent prognostic marker for predicting overall survival and disease free survival of HCC patients. Overexpression of DDR2 is associated with p-DDR2 amplification. In vitro studies showed that DDR2 facilitates HCC cell invasion, migration and EMT via activating ERK2 and stabilizing SNAIL1. DDR2 can up-regulate MT1-MMP and MMP2 expression through ERK2/SNAIL1 signaling in HCC. Additionally, collagen I can induce DDR2/ERK2/SNAIL1 signaling activation in HCC cells. CONCLUSIONS: Our findings suggest that DDR2 plays an important role in promoting HCC cell invasion and migration, and may serve as a novel therapeutic target in HCC. PMID- 26362311 TI - The role of antigen presenting cells in the induction of HIV-1 latency in resting CD4(+) T-cells. AB - BACKGROUND: Combination antiretroviral therapy (cART) is able to control HIV-1 viral replication, however long-lived latent infection in resting memory CD4(+) T cells persist. The mechanisms for establishment and maintenance of latent infection in resting memory CD4(+) T-cells remain unclear. Previously we have shown that HIV-1 infection of resting CD4(+) T-cells co-cultured with CD11c(+) myeloid dendritic cells (mDC) produced a population of non-proliferating T-cells with latent infection. Here we asked whether different antigen presenting cells (APC), including subpopulations of DC and monocytes, were able to induce post integration latent infection in resting CD4(+) T-cells, and examined potential cell interactions that may be involved using RNA-seq. RESULTS: mDC (CD1c(+)), SLAN(+) DC and CD14(+) monocytes were most efficient in stimulating proliferation of CD4(+) T-cells during syngeneic culture and in generating post-integration latent infection in non-proliferating CD4(+) T-cells following HIV-1 infection of APC-T cell co-cultures. In comparison, plasmacytoid DC (pDC) and B-cells did not induce latent infection in APC-T-cell co-cultures. We compared the RNA expression profiles of APC subpopulations that could and could not induce latency in non proliferating CD4(+) T-cells. Gene expression analysis, comparing the CD1c(+) mDC, SLAN(+) DC and CD14(+) monocyte subpopulations to pDC identified 53 upregulated genes that encode proteins expressed on the plasma membrane that could signal to CD4(+) T-cells via cell-cell interactions (32 genes), immune checkpoints (IC) (5 genes), T-cell activation (9 genes), regulation of apoptosis (5 genes), antigen presentation (1 gene) and through unknown ligands (1 gene). CONCLUSIONS: APC subpopulations from the myeloid lineage, specifically mDC subpopulations and CD14(+) monocytes, were able to efficiently induce post integration HIV-1 latency in non-proliferating CD4(+) T-cells in vitro. Inhibition of key pathways involved in mDC-T-cell interactions and HIV-1 latency may provide novel targets to eliminate HIV-1 latency. PMID- 26362314 TI - An efficient identification approach for stable and unstable nonlinear systems using Colliding Bodies Optimization algorithm. AB - This paper presents an efficient approach to identify different stable and practically useful Hammerstein models as well as unstable nonlinear process along with its stable closed loop counterpart with the help of an evolutionary algorithm as Colliding Bodies Optimization (CBO) optimization algorithm. The performance measures of the CBO based optimization approach such as precision, accuracy are justified with the minimum output mean square value (MSE) which signifies that the amount of bias and variance in the output domain are also the least. It is also observed that the optimization of output MSE in the presence of outliers has resulted in a very close estimation of the output parameters consistently, which also justifies the effective general applicability of the CBO algorithm towards the system identification problem and also establishes the practical usefulness of the applied approach. Optimum values of the MSEs, computational times and statistical information of the MSEs are all found to be the superior as compared with those of the other existing similar types of stochastic algorithms based approaches reported in different recent literature, which establish the robustness and efficiency of the applied CBO based identification scheme. PMID- 26362316 TI - First conference on cancer immunotherapy gets "explosion of interest". PMID- 26362315 TI - Optimal detection of hypothyroidism in early stage laryngeal cancer treated with radiotherapy. AB - BACKGROUND: Hypothyroidism following radiation therapy (RT) for treatment of Head and Neck Cancer (HNC) is a common occurrence. Rates of hypothyroidism following RT for Early Stage Laryngeal Squamous Cell Carcinoma (ES-LSCC) are among the highest. Although routine screening for hypothyroidism is recommended; its optimal schedule has not yet been established. We aim to determine the prevalence and optimal timing of testing for hypothyroidism in ES-LSCC treated with RT. METHOD: We conducted a population-based cohort study. Data was extracted from a prospective provincial head and neck cancer database. Demographic, survival data, and pre- and post-treatment thyroid stimulating hormone (TSH) levels were obtained for patients diagnosed with ES-LSCC from 2008-2012. Inclusion criteria consisted of patients diagnosed clinically with ES-LSCC (T1 or 2, N0, M0) treated with curative intent. Patients were excluded if there was a history of hypothyroidism before the treatment or any previous history of head and neck cancers. RESULTS: Ninety-five patients were included in this study. Mean age was 66.1 years (range: 44.0-88.0 years) and 82.3% of patients were male. Glottis was the most common subsite at 77.9% and the average follow-up was 40 months (Range: 12-56 months). Five-year overall survival generated using the Kaplan-Meier method was 79%. Incidence of hypothyroidism after RT was found to be 46.9%. The greatest frequency of developing hypothyroidism was at 12 months. CONCLUSIONS: We found a high prevalence of hypothyroidism for ES-LSCC treated with RT, with the highest rate at 12 months. Consequently, we recommend possible routine screening for hypothyroidism using TSH level starting at 12 months. To our knowledge, this is the first study to suggest the optimal timing for the detection of hypothyroidism. PMID- 26362317 TI - Comprehensive Assessment of Oxidatively Induced Modifications of DNA in a Rat Model of Human Wilson's Disease. AB - Defective copper excretion from hepatocytes in Wilson's disease causes accumulation of copper ions with increased generation of reactive oxygen species via the Fenton-type reaction. Here we developed a nanoflow liquid chromatography nanoelectrospray ionization-tandem mass spectrometry coupled with the isotope dilution method for the simultaneous quantification of oxidatively induced DNA modifications. This method enabled measurement, in microgram quantities of DNA, of four oxidative stress-induced lesions, including direct ROS-induced purine cyclonucleosides (cPus) and two exocyclic adducts induced by byproducts of lipid peroxidation, i.e. 1,N(6)-etheno-2'-deoxyadenosine (epsilondA) and 1,N(2)-etheno 2'-deoxyguanosine (epsilondG). Analysis of liver tissues of Long-Evans Cinnamon rats, which constitute an animal model of human Wilson's disease, and their healthy counterparts [i.e. Long-Evans Agouti rats] showed significantly higher levels of all four DNA lesions in Long-Evans Cinnamon than Long-Evans Agouti rats. Moreover, cPus were present at much higher levels than epsilondA and epsilondG lesions. In contrast, the level of 5-hydroxymethyl-2'-deoxycytidine (5 HmdC), an oxidation product of 5-methyl-2'-deoxycytidine (5-mdC), was markedly lower in the liver tissues of Long-Evans Cinnamon than Long-Evans Agouti rats, though no differences were observed for the levels of 5-mdC. In vitro biochemical assay showed that Cu(2+) ions could directly inhibit the activity of Tet enzymes. Together, these results suggest that aberrant copper accumulation may perturb genomic stability by elevating oxidatively induced DNA lesions, and by altering epigenetic pathways of gene regulation. PMID- 26362318 TI - New Regulators of Clathrin-Mediated Endocytosis Identified in Saccharomyces cerevisiae by Systematic Quantitative Fluorescence Microscopy. AB - Despite the importance of clathrin-mediated endocytosis (CME) for cell biology, it is unclear if all components of the machinery have been discovered and many regulatory aspects remain poorly understood. Here, using Saccharomyces cerevisiae and a fluorescence microscopy screening approach we identify previously unknown regulatory factors of the endocytic machinery. We further studied the top scoring protein identified in the screen, Ubx3, a member of the conserved ubiquitin regulatory X (UBX) protein family. In vivo and in vitro approaches demonstrate that Ubx3 is a new coat component. Ubx3-GFP has typical endocytic coat protein dynamics with a patch lifetime of 45 +/- 3 sec. Ubx3 contains a W-box that mediates physical interaction with clathrin and Ubx3-GFP patch lifetime depends on clathrin. Deletion of the UBX3 gene caused defects in the uptake of Lucifer Yellow and the methionine transporter Mup1 demonstrating that Ubx3 is needed for efficient endocytosis. Further, the UBX domain is required both for localization and function of Ubx3 at endocytic sites. Mechanistically, Ubx3 regulates dynamics and patch lifetime of the early arriving protein Ede1 but not later arriving coat proteins or actin assembly. Conversely, Ede1 regulates the patch lifetime of Ubx3. Ubx3 likely regulates CME via the AAA-ATPase Cdc48, a ubiquitin-editing complex. Our results uncovered new components of the CME machinery that regulate this fundamental process. PMID- 26362319 TI - Termination of Replication Stress Signaling via Concerted Action of the Slx4 Scaffold and the PP4 Phosphatase. AB - In response to replication stress, signaling mediated by DNA damage checkpoint kinases protects genome integrity. However, following repair or bypass of DNA lesions, checkpoint signaling needs to be terminated for continued cell cycle progression and proliferation. In budding yeast, the PP4 phosphatase has been shown to play a key role in preventing hyperactivation of the checkpoint kinase Rad53. In addition, we recently uncovered a phosphatase-independent mechanism for downregulating Rad53 in which the DNA repair scaffold Slx4 decreases engagement of the checkpoint adaptor Rad9 at DNA lesions. Here we reveal that proper termination of checkpoint signaling following the bypass of replication blocks imposed by alkylated DNA adducts requires the concerted action of these two fundamentally distinct mechanisms of checkpoint downregulation. Cells lacking both SLX4 and the PP4-subunit PPH3 display a synergistic increase in Rad53 signaling and are exquisitely sensitive to the DNA alkylating agent methyl methanesulfonate, which induces replication blocks and extensive formation of chromosomal linkages due to template switching mechanisms required for fork bypass. Rad53 hypersignaling in these cells seems to converge to a strong repression of Mus81-Mms4, the endonuclease complex responsible for resolving chromosomal linkages, thus explaining the selective sensitivity of slx4Delta pph3Delta cells to alkylation damage. Our results support a model in which Slx4 acts locally to downregulate Rad53 activation following fork bypass, while PP4 acts on pools of active Rad53 that have diffused from the site of lesions. We propose that the proper spatial coordination of the Slx4 scaffold and PP4 action is crucial to allow timely activation of Mus81-Mms4 and, therefore, proper chromosome segregation. PMID- 26362320 TI - Assessment at UK medical schools varies substantially in volume, type and intensity and correlates with postgraduate attainment. AB - BACKGROUND: In the United Kingdom (UK), medical schools are free to develop local systems and policies that govern student assessment and progression. Successful completion of an undergraduate medical degree results in the automatic award of a provisional licence to practice medicine by the General Medical Council (GMC). Such a licensing process relies heavily on the assumption that individual schools develop similarly rigorous assessment policies. Little work has evaluated variability of undergraduate medical assessment between medical schools. That absence is important in the light of the GMC's recent announcement of the introduction of the UKMLA (UK Medical Licensing Assessment) for all doctors who wish to practise in the UK. The present study aimed to quantify and compare the volume, type and intensity of summative assessment across medicine (A100) courses in the United Kingdom, and to assess whether intensity of assessment correlates with the postgraduate attainment of doctors from these schools. METHODS: Locally knowledgeable students in each school were approached to take part in guided questionnaire interviews via telephone or Skype(TM). Their understanding of assessment at their medical school was probed, and later validated with the assessment department of the respective medical school. We gathered data for 25 of 27 A100 programmes in the UK and compared volume, type and intensity of assessment between schools. We then correlated these data with the mean first attempt score of graduates sitting MRCGP and MRCP(UK), as well as with UKFPO selection measures. RESULTS: The median written assessment volume across all schools was 2000 min (mean = 2027, SD = 586, LQ = 1500, UQ = 2500, range = 1000 3200) and 1400 marks (mean = 1555, SD = 463, LQ = 1200, UQ = 1800, range = 1100 2800). The median practical assessment volume was 400 min (mean = 472, SD = 207, LQ = 400, UQ = 600, range = 200-1000). The median intensity (minutes per mark ratio) of summative written assessment was 1.24 min per mark (mean = 1.28, SD = 0.30, LQ = 1.11, UQ = 1.37, range = 0.85-2.08). An exploratory analysis suggested a significant correlation of total assessment time with mean first-attempt score on both the knowledge and the clinical assessments of MRCGP and of MRCP(UK). CONCLUSIONS: There are substantial differences in the volume, format and intensity of undergraduate assessment between UK medical schools. These findings suggest a potential for differences in the reliability of detecting poorly performing students, or differences in identifying and stratifying academically equivalent students for ranking in the Foundation Programme Application System (FPAS). Furthermore, these differences appear to directly correlate with performance in postgraduate examinations. Taken together, our findings highlight highly variable local assessment procedures that warrant further investigation to establish their potential impact on students. PMID- 26362322 TI - Improving Retention in HIV Care: A Cost-effective Strategy to Turn the Tide on HIV and AIDS in the United States. PMID- 26362321 TI - The Epidemiologic and Economic Impact of Improving HIV Testing, Linkage, and Retention in Care in the United States. AB - BACKGROUND: Recent guidelines advocate early antiretroviral therapy (ART) to decrease human immunodeficiency virus (HIV) morbidity and prevent transmission, but suboptimal engagement in care may compromise impact. We sought to determine the economic and epidemiologic impact of incomplete engagement in HIV care in the United States. METHODS: We constructed a dynamic transmission model of HIV among US adults (aged 15-65 years) and conducted a cost-effectiveness analysis of improvements along the HIV care continuum : We evaluated enhanced HIV testing (annual for high-risk groups), increased 3-month linkage to care (to 90%), and improved retention (50% relative reduction in yearly disengagement and 50% increase in reengagement). Our primary outcomes were HIV incidence, mortality, costs and quality-adjusted life-years (QALYs). RESULTS: Despite early ART initiation, a projected 1.39 million (95% uncertainty range [UR], 0.91-2.2 million) new HIV infections will occur at a (discounted) cost of $256 billion ($199-298 billion) over 2 decades at existing levels of HIV care engagement. Enhanced testing with increased linkage has modest epidemiologic benefits and could reduce incident HIV infections by 21% (95% UR, 13%-26%) at a cost of $65 700 per QALY gained ($44 500-111 000). By contrast, comprehensive improvements that couples enhanced testing and linkage with improved retention would reduce HIV incidence by 54% (95% UR, 37%-68%) and mortality rate by 64% (46%-78%), at a cost-effectiveness ratio of $45 300 per QALY gained ($27 800-72 300). CONCLUSIONS: Failure to improve engagement in HIV care in the United States leads to excess infections, treatment costs, and deaths. Interventions that improve not just HIV screening but also retention in care are needed to optimize epidemiologic impact and cost-effectiveness. PMID- 26362323 TI - Mechano-stimulated modifications in the chloroplast antioxidant system and proteome changes are associated with cold response in wheat. AB - BACKGROUND: Mechanical wounding can cause morphological and developmental changes in plants, which may affect the responses to abiotic stresses. However, the mechano-stimulation triggered regulation network remains elusive. Here, the mechano-stimulation was applied at two different times during the growth period of wheat before exposing the plants to cold stress (5.6 degrees C lower temperature than the ambient temperature, viz., 5.0 degrees C) at the jointing stage. RESULTS: Results showed that mechano-stimulation at the Zadoks growth stage 26 activated the antioxidant system, and substantially, maintained the homeostasis of reactive oxygen species. In turn, the stimulation improved the electron transport and photosynthetic rate of wheat plants exposed to cold stress at the jointing stage. Proteomic and transcriptional analyses revealed that the oxidative stress defense, ATP synthesis, and photosynthesis-related proteins and genes were similarly modulated by mechano-stimulation and the cold stress. CONCLUSIONS: It was concluded that mechano-stimulated modifications of the chloroplast antioxidant system and proteome changes are related to cold tolerance in wheat. The findings might provide deeper insights into roles of reactive oxygen species in mechano-stimulated cold tolerance of photosynthetic apparatus, and be helpful to explore novel approaches to mitigate the impacts of low temperature occurring at critical developmental stages. PMID- 26362325 TI - Collaborative derivation of reference intervals for major clinical laboratory tests in Japan. AB - OBJECTIVES: Three multicentre studies of reference intervals were conducted recently in Japan. The Committee on Common Reference Intervals of the Japan Society of Clinical Chemistry sought to establish common reference intervals for 40 laboratory tests which were measured in common in the three studies and regarded as well harmonized in Japan. METHODS: The study protocols were comparable with recruitment mostly from hospital workers with body mass index <=28 and no medications. Age and sex distributions were made equal to obtain a final data size of 6345 individuals. Between-subgroup differences were expressed as the SD ratio (between-subgroup SD divided by SD representing the reference interval). Between-study differences were all within acceptable levels, and thus the three datasets were merged. RESULTS: By adopting SD ratio >=0.50 as a guide, sex-specific reference intervals were necessary for 12 assays. Age-specific reference intervals for females partitioned at age 45 were required for five analytes. The reference intervals derived by the parametric method resulted in appreciable narrowing of the ranges by applying the latent abnormal values exclusion method in 10 items which were closely associated with prevalent disorders among healthy individuals. Sex- and age-related profiles of reference values, derived from individuals with no abnormal results in major tests, showed peculiar patterns specific to each analyte. CONCLUSION: Common reference intervals for nationwide use were developed for 40 major tests, based on three multicentre studies by advanced statistical methods. Sex- and age-related profiles of reference values are of great relevance not only for interpreting test results, but for applying clinical decision limits specified in various clinical guidelines. PMID- 26362326 TI - [Cytology in uropathological diagnostics]. AB - Cytology in uropathological diagnostics is mainly performed for oncological purposes. The assessment of malignancy by urothelial cell morphology is therefore decisive; however, cytology is only sensitive enough to detect high-grade tumor cells and the different low-grade tumors cannot be reliably diagnosed. Thus, the four-tier classification system of cytological findings (i.e. negative, atypical cells but significance uncertain, suspicious and positive) refers to high-grade tumor cells only. Furthermore, for valid cytological diagnostics not only the cytological specimen but also clinical information on cystoscopy findings and, if applicable, a biopsy should be evaluated together. In difficult differential diagnostic settings, e.g. differentiation between reactive versus neoplastic atypia or difficult to access lesions in the upper urinary tract, additional fluorescence in situ hybridization of cytological preparations might be helpful. At the moment there are no indications for further immunocytology or additional biomarker tests. PMID- 26362327 TI - [Novel biomarkers in renal cell carcinoma. Identification and functional characterization]. AB - Due to advanced imaging techniques, renal cell carcinoma (RCC) is now identified earlier, often in localized stages. As a result, nephron-sparing surgical resection is possible in most cases. The development of new targeted therapies has changed the way metastatic RCC is treated. Despite this positive trend with improved survival rates and expanding treatment options, reliable biomarkers for better predicting disease course are lacking. These are urgently needed to enable personalized therapy based on the treatment-associated risks, the presence of comorbidities, and molecular tumor characteristics. We were able to show that proteins with a regulatory influence on apoptotic signal cascades represent not only promising prognostic markers, but also interesting targets for new therapeutic approaches. Furthermore, our data demonstrate that molecular tests are necessary to correctly classify a RCC with Xp11.2 translocation, since in addition to translocation, amplification can also result in TFE3 activation. Translational research with RCC biomarker identification and establishment, as well as molecular characterization and subtyping of RCCs is required to guide therapeutic decisions and enable personalized medicine in RCC patients. PMID- 26362328 TI - Characterization and Functional Analysis of Pyrabactin Resistance-Like Abscisic Acid Receptor Family in Rice. AB - BACKGROUND: Abscisic acid (ABA) plays crucial roles in regulating plant growth and development, especially in responding to abiotic stress. The pyrabactin resistance-like (PYL) abscisic acid receptor family has been identified and widely characterized in Arabidopsis. However, PYL families in rice were largely unknown. In the present study, 10 out of 13 PYL orthologs in rice (OsPYL) were isolated and investigated. RESULTS: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis showed that expression of OsPYL genes is tissue specific and display differential response to ABA treatment, implying their functional diversity. The interaction between 10 OsPYL members and 5 protein phosphatase 2C in rice (OsPP2C) members was investigated in yeast two-hybrid and tobacco transient expression assays, and an overall interaction map was generated, which was suggestive of the diversity and complexity of ABA-sensing signaling in rice. To study the biological function of OsPYLs, two OsPYL genes (OsPYL3 and OsPYL9) were overexpressed in rice. Phenotypic analysis of OsPYL3 and OsPYL9 transgenic rice showed that OsPYLs positively regulated the ABA response during the seed germination. More importantly, the overexpression of OsPYL3 and OsPYL9 substantially improved drought and cold stress tolerance in rice. CONCLUSION: Taken together, we comprehensively uncovered the properties of OsPYLs, which may be good candidates for the improvement of abiotic stress tolerance in rice. PMID- 26362329 TI - Psychrobacter fjordensis sp. nov., a psychrotolerant bacterium isolated from an Arctic fjord in Svalbard. AB - A Gram-negative, non-motile, non-spore-forming, psychrotolerant and halotolerant bacterium designated BSw21516B(T), was obtained from seawater in Kongsfjorden, a glacial fjord in the Arctic Svalbard and subjected to taxonomic analysis using a polyphasic approach. This bacterium was observed to optimally grow at 25-29 degrees C; between at 4 and 34 degrees C, but not at >35 degrees C; and in the presence of 0-8 % (w/v) NaCl at an optimum concentration of 2-5 % (w/v) NaCl. Strain BSw21516B(T) was found to contain Ubiquinone-8 (Q-8) as a predominant respiratory lipoquinone and C18:1 omega9c and summed feature 3 (C16:1 omega7c and/or iso-C15:0 2-OH) as predominant cellular fatty acids. Phylogenetic analysis of 16S rRNA and gyrB gene sequences showed that this isolate belongs to the genus Psychrobacter and is closely related to Psychrobacter fozii LMG 21280(T), which was isolated from a sediment sample in Antarctica. DNA hybridization experiments revealed a low level of DNA-DNA relatedness (less than 58.6 %) between strain BSw21516B(T) and its closest relatives. Based on these results a new species Psychrobacter fjordensis sp. nov. is proposed (type strain BSw21516B(T) = KCTC 42279(T) = CCTCC AB 2014020(T)). PMID- 26362330 TI - A heavy metal tolerant novel bacterium, Bacillus malikii sp. nov., isolated from tannery effluent wastewater. AB - The taxonomic position of a Gram-stain positive and heavy metal tolerant bacterium, designated strain NCCP-662(T), was investigated by polyphasic characterisation. Cells of strain NCCP-662(T) were observed to be rod to filamentous shaped, motile and strictly aerobic, and to grow at 10-50 degrees C (optimum 30-37 degrees C) and at pH range of 6-10 (optimum pH 7-8). The strain was found to be able to tolerate 0-12 % NaCl (w/v) and heavy metals (Cr 1200 ppm, Pb 1800 ppm and Cu 1200 ppm) in tryptic soya agar medium. The phylogenetic analysis based on the 16S rRNA gene sequence of strain NCCP-662(T) showed that it belongs to the genus Bacillus and showed high sequence similarity (98.2 and 98.0 %, respectively) with the type strains of Bacillus niabensis 4T19(T) and Bacillus halosaccharovorans E33(T). The chemotaxonomic data showed that the major quinone is MK-7; the predominant cellular fatty acids are anteiso-C15 :0, iso-C14:0, iso C16:0 and C16:0 and iso-C15:0; the major polar lipids are diphosphatidylglycerol, phosphatidylglycerol along with several unidentified glycolipids, phospholipids and polar lipids. The DNA G+C content was determined to be 36.9 mol%. These data also support the affiliation of strain NCCP-662(T) with the genus Bacillus. The level of DNA-DNA relatedness between strain NCCP-662(T) and B. niabensis JCM 16399(T) was 20.5 +/- 0.5 %. On the basis of physiological and biochemical characteristics, phylogenetic analyses and DNA-DNA hybridization data, strain NCCP-662(T) can be clearly differentiated from the validly named Bacillus species and thus represents a new species, for which the name Bacillus malikii sp. nov. is proposed with the type strain NCCP-662(T) (= LMG 28369(T) = DSM 29005(T) = JCM 30192(T)). PMID- 26362331 TI - Transcriptomic response of Saccharomyces cerevisiae for its adaptation to sulphuric acid-induced stress. AB - In bioethanol production plants, yeast cells are generally recycled between fermentation batches by using a treatment with sulphuric acid at a pH ranging from 2.0 to 2.5. We have previously shown that Saccharomyces cerevisiae cells exposed to sulphuric acid treatment induce the general stress response pathway, fail to activate the protein kinase A signalling cascade and requires the mechanisms of cell wall integrity and high osmolarity glycerol pathways in order to survive in this stressful condition. In the present work, we used transcriptome-wide analysis as well as physiological assays to identify the transient metabolic responses of S. cerevisiae under sulphuric acid treatment. The results presented herein indicate that survival depends on a metabolic reprogramming of the yeast cells in order to assure the yeast cell viability by preventing cell growth under this harmful condition. It involves the differential expression of a subset of genes related to cell wall composition and integrity, oxidation-reduction processes, carbohydrate metabolism, ATP synthesis and iron uptake. These results open prospects for application of this knowledge in the improvement of industrial processes based on metabolic engineering to select yeasts resistant to acid treatment. PMID- 26362332 TI - Kocuria subflava sp. nov., isolated from marine sediment from the Indian Ocean. AB - A novel Gram-staining positive, catalase-positive, oxidase-negative, aerobic, non motile coccus, designated strain YIM 13062(T), was isolated from a marine sediment sample collected from the Indian Ocean. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain YIM 13062(T) belongs to the genus Kocuria, and is closely related to Kocuria polaris NBRC 103063(T) (97.8 % similarity), Kocuria rosea NBRC 3768(T) (97.6 % similarity) and Kocuria carniphila JCM 14118(T) (97.4 % similarity). The strain grew optimally at 28 degrees C, pH 8.0 and in the presence of 2-4 % (w/v) NaCl. Cell-wall peptidoglycan type was Lys-Ala3 (type A3alpha). The major isoprenoid quinones were MK-6(H2) and MK-7(H2). The polar lipids of strain YIM 13062(T) consisted of diphosphatidylglycerol (DPG), phosphatidylglycerol (PG), one unidentified phospholipid (PL), one unidentified aminophospholipid (APL), two unidentified aminolipids (AL) and four unidentified lipids (L). Major fatty acids of the novel isolate were anteiso-C15:0, iso-C14:0 and C18:1 2OH. The genomic DNA G+C content of strain YIM 13062(T) was 68.0 mol%. The level of DNA-DNA relatedness between strain YIM 13062(T) and K. polaris NBRC 103063(T), K. rosea NBRC 3768(T), K. carniphila JCM 14118(T) were 53.2, 48.8 and 42.6 %, respectively. On the basis of genotypic and phenotypic data, it is apparent that strain YIM 13062(T) represents a novel species of the genus Kocuria, for which the name Kocuria subflava sp. nov. is proposed. The type strain is YIM 13062(T) (=CGMCC 4.7252(T)=KCTC 39547(T)). PMID- 26362333 TI - Ruxolitinib: A Review in Polycythaemia Vera. AB - Ruxolitinib (Jakavi((r)), Jakafi((r))) is an orally administered, first-in-class Janus Kinase (JAK) 1 and 2 inhibitor that was recently approved for the treatment of patients with polycythaemia vera (PV) who have responded inadequately to or are intolerant of hydroxyurea. By inhibiting JAK 1 and 2, ruxolitinib reduces hyperactive JAK-signal transducers and activators of transcription (STAT) signalling that is implicated in the pathogenesis of PV. This article briefly reviews the pharmacology of the drug, focusing on its clinical use in patients with PV. In the phase III RESPONSE trial in PV patients who had an inadequate response to or unacceptable adverse effects from hydroxyurea, ruxolitinib was superior to best available therapy in reducing haematocrit without phlebotomy and reducing spleen size after 32 weeks of treatment. Ruxolitinib was also associated with reducing leukocyte and platelet counts and improving symptoms. Patient follow-up demonstrated that response to ruxolitinib was durable, including preliminary results after up to 80 weeks of treatment. The drug is generally well tolerated, although mild to moderate anaemia, thrombocytopenia and lymphopenia were common in the RESPONSE trial. These effects can usually be managed with dosage modification and did not lead to therapy discontinuation in the RESPONSE trial. Thus, for a subgroup of PV patients for whom few treatment options have existed previously, ruxolitinib provides a valid option. PMID- 26362334 TI - The importance of effective communication in interprofessional practice: perspectives of maternity clinicians. AB - Midwives and doctors require effective information-sharing strategies to provide safe and evidence-based care for women and infants, but this can be difficult to achieve. This article describes maternity care professionals' perceptions of communication in their current workplace in Australia. We invoke social identity theory (SIT) to explore how these perceptions affect interprofessional practice. A survey was conducted with 337 participants (281 midwives and 56 doctors). Using exploratory factor analysis we developed three scales that measured interprofessional workplace practice collaboration. Results indicated an intergroup environment in maternity care in which the professionals found exchange of ideas difficult, and where differences with respect to decision making and professional skills were apparent. Although scores on some measures of collaboration were high, the two professions differed on their ratings of the importance of team behaviors, information sharing, and interprofessional socialization as indicators of collaborative practice. These results highlight the complexities among maternity care providers with different professional identities, and demonstrate the impact of professional identity on interprofessional communication. PMID- 26362335 TI - Prediction of disability progression in fingolimod-treated patients. AB - PURPOSE: The aim of the study was to evaluate whether early disease activity during fingolimod treatment could predict disease progression in patients with relapsing-remitting multiple sclerosis (RRMS). METHODS: We included RRMS patients who received fingolimod for at least 12 months with a >=36 months of follow-up. Early disease activity was assessed by the modified Rio score (MRS). Association between MRS at 12 months and time to disability progression over the following two years was assessed using Kaplan-Meier survival curves analysis and Cox proportional hazards model. RESULTS: At 1 year from starting treatment, 14 (58.3%), 5 (20.8%), 3 (12.5%) and 2 (8.3%) subjects had a MRS=0, 1, 2, and 3, respectively. The risk of disability progression in the next 2 years was associated to the MRS and increased from 21.1% in patients with MRS=0-1 to 80% in those with MRS>=2 (adjusted HR=19.67; 95% CI=2.30-167.79; p=0.006). CONCLUSIONS: Early disease activity is suggested to be associated with the risk of disease progression in patients receiving fingolimod and MRS could be a reliable tool to identify the subjects at higher risk of unfavorable course. PMID- 26362336 TI - Quantitative evaluation of gait ataxia by accelerometers. AB - An appropriate biomarker for spinocerebellar degeneration (SCD) has not been identified. Here, we performed gait analysis on patients with pure cerebellar type SCD and assessed whether the obtained data could be used as a neurophysiological biomarker for cerebellar ataxia. We analyzed 25 SCD patients, 25 patients with Parkinson's disease as a disease control, and 25 healthy control individuals. Acceleration signals during 6 min of walking and 1 min of standing were measured by two sets of triaxial accelerometers that were secured with a fixation vest to the middle of the lower and upper back of each subject. We extracted two gait parameters, the average and the coefficient of variation of motion trajectory amplitude, from each acceleration component. Then, each component was analyzed by correlation with the Scale for the Assessment and Rating of Ataxia (SARA) and the Berg Balance Scale (BBS). Compared with the gait control of healthy subjects and concerning correlation with severity and disease specificity, our results suggest that the average amplitude of medial-lateral (upper back) of straight gait is a physiological biomarker for cerebellar ataxia. Our results suggest that gait analysis is a quantitative and concise evaluation scale for the severity of cerebellar ataxia. PMID- 26362337 TI - Thalamus and MS: Role of thalamic atrophy in daily living and employment activities of MS patients. PMID- 26362338 TI - Usefulness of intraventricular infusion of antifungal drugs through Ommaya reservoirs for cryptococcal meningitis treatment. AB - INTRODUCTION: Cryptococcal meningitis is a severe infection among immunosuppressed individuals, with a high mortality rate. Although amphotericin B is the first-choice drug for treatment, its use is restricted when adverse effects are clinically problematic. The usefulness of intraventricular infusion of antifungal drugs through Ommaya reservoirs for cryptococcal meningitis treatment has been unconfirmed. We evaluated the efficacy of intraventricular infusion of amphotericin B through Ommaya reservoirs. MATERIALS AND METHODS: We retrospectively analyzed 10 consecutive patients with cryptococcal meningitis who were refractory to systemic administration of antifungal drugs. RESULTS: Fever or nausea occurred in most patients. However, no patient complained of serious complications such as renal toxicity. Seven patients recovered completely or partially, whereas three patients died. CONCLUSIONS: To establish the efficacy of the intraventricular infusion of antifungal drugs through Ommaya reservoirs for cryptococcal meningitis, a prospective investigation should be designed to compare those treated according to the updated guidelines and those treated with antifungal drugs through the Ommaya reservoirs. PMID- 26362339 TI - Diagnostic value of hyperfibrinogenemia as a predictive factor for appendiceal perforation in acute appendicitis. AB - BACKGROUND: Acute appendicitis is one of the most common emergency requiring operation. As the first discovered coagulation factor, plasma fibrinogen frequently increases with inflammation due to the activation of coagulation. The aim of this retrospective study was to investigate the diagnostic value of hyperfibrinogenemia as a preoperative laboratory marker for appendiceal perforation in patients with acute appendicitis. MATERIALS AND METHODS: We identified 455 patients (202 females, 253 males; mean age, 31.7 years) with histologically confirmed acute appendicitis who underwent laparoscopic or open appendectomy. Results of preoperative laboratory values and post-operative histologic results were analysed retrospectively. A multivariate logistic regression model was performed to determine patient's age and laboratory tests associated with perforated appendicitis. RESULT: Mean plasma fibrinogen level of all patients was 3.99 g/L (1.41 SD; range, 1.73-10.6 g/L; median, 3.69 g/L). Patients with appendiceal perforation had a mean fibrinogen level of 5.72 g/L (1.52 SD; range, 3.38-10.04 g/L; median, 5.28 g/L), which was significantly higher than those with nonperforated groups (P = 0.001). Multivariate analysis showed fibrinogen and D-dimer were associated with perforation (P = 0.001, P = 0.014, respectively). Areas under the receiver operating characteristic curve of fibrinogen for discriminating acute perforated appendicitis from non-perforated groups were larger than white blood cell and D-dimer. CONCLUSIONS: Hyperfibrinogenemia was common in patients with acute appendicitis and fibrinogen may be useful as a predictive factor for appendiceal perforation. PMID- 26362340 TI - Apamin-Sensitive K+ Current Upregulation in Volume-Overload Heart Failure is Associated with the Decreased Interaction of CK2 with SK2. AB - Recent studies have shown that the sensitivity of apamin-sensitive K(+) current (I KAS, mediated by apamin-sensitive small conductance calcium-activated potassium channels subunits) to intracellular Ca(2+) is increased in heart failure (HF), leading to I KAS upregulation, action potential duration shortening, early after depolarization, and recurrent spontaneous ventricular fibrillation. We hypothesized that casein kinase 2 (CK2) interacted with small conductance calcium-activated potassium channels (SK) is decreased in HF, and protein phosphatase 2A (PP2A) is increased on the opposite, upregulating the sensitivity of I KAS to intracellular Ca(2+) in HF. Rat model of volume-overload HF was established by an abdominal arteriovenous fistula procedure. The expression of SK channels, PP2A and CK2 was detected by Western blot analysis. Interaction and colocalization of CK2 with SK channel were detected by co immunoprecipitation analysis and double immunofluorescence staining. In HF rat left ventricle, SK3 was increased by 100 % (P < 0.05), and SK2 was not significantly changed. PP2A protein was increased by 94.7 % in HF rats (P < 0.05), whereas the level of CK2 was almost unchanged. We found that CK2 colocalized with SK2 and SK3 in rat left ventricle. With anti-CK2alpha antibody, SK2 and SK3 were immunoprecipitated, the level of precipitated SK2 decreased by half, whereas precipitated SK3 was almost unchanged. In conclusion, the increased expression of total PP2A and decreased interaction of CK2 with SK2 may underlie enhanced sensitivity of I KAS to intracellular Ca(2+) in volume-overload HF rat. PMID- 26362341 TI - Ouabain Modulates the Lipid Composition of Hippocampal Plasma Membranes from Rats with LPS-induced Neuroinflammation. AB - The effects of ouabain (OUA) and lipopolysaccharide (LPS) in vivo on hippocampal membranes (RHM) of Wistar male rats aged 3 months were analyzed. After intraperitoneal (i.p.) injection of OUA only, LPS only, OUA plus LPS, or saline, the content of proteins, phospholipids, cholesterol and gangliosides from RHM was analyzed. The total protein and cholesterol contents of RHM were not significantly affected by OUA or LPS for the experimentally paired groups. In contrast, total phospholipids and gangliosides were strongly modulated by either OUA or LPS treatments. LPS reduced the total phospholipids (roughly 23 %) and increased the total gangliosides (approximately 40 %). OUA alone increased the total phospholipids (around 23 %) and also the total gangliosides (nearly 34 %). OUA pretreatment compensated the LPS-induced changes, preserving the total phospholipids and gangliosides around the same levels of the control. Thus, an acute treatment with OUA not only modulated the composition of hippocampal membranes from 3-month-old rats, but also was apparently able to counteract membrane alterations resulting from LPS-induced neuroinflammation. This study demonstrates for the first time that the OUA capacity modulates the lipid composition of hippocampal plasma membranes from rats with LPS-induced neuroinflammation. PMID- 26362342 TI - Usefulness of EUS-guided fine needle aspiration biopsy in the diagnosis of suspected or recurring lymphoproliferative disorders. AB - BACKGROUND: EUS-guided fine needle aspiration biopsy (EUS-FNAB) of deep-seated lymphadenopathy is proposed to identify lymphoproliferative disorders when no superficial lesion is accessible. METHODS: We analyzed prospectively collected data of 115 EUS-FNABs from 73 thoracic or abdomino-pelvic targets in 52 patients with suspected lymphoproliferative disorders (LPDs) between January 2005 and May 2011 from a single institution. Conventional histology and immunohistochemistry procedures were performed on samples. RESULTS: No complications were recorded. An LPD was identified in 29 cases and ruled out in 21 cases. In 2 cases the analysis was negative, but an LPD was identified using a secondary procedure. For the identification of LPDs irrespective of subtype, this procedure has positive and negative predictive values of 100% and 91.3% respectively, with 93.6% sensitivity and 100% specificity. In 31 patients finally diagnosed with LPDs, an accurate diagnosis meeting the 2008 World Health Organization classification criteria was established in 21 (68%) cases, success being significantly associated with target size above 30 mm in multivariate analysis (odds ratio 7.47; p = 0.05). CONCLUSION: EUS-FNAB of deep-seated lymphadenopathy with conventional morphological assessment appears to have a high diagnostic value for LPD identification and can obviate invasive surgery. A sub-classification was possible in two thirds of the cases. PMID- 26362343 TI - Neoadjuvant dasatinib for muscle-invasive bladder cancer with tissue analysis of biologic activity. AB - OBJECTIVES: Preclinical urothelial carcinoma models suggest activity of dasatinib, an oral SRC-family kinase (SFK) inhibitor. We sought to determine the feasibility and biologic activity of neoadjuvant dasatinib (Neo-D) in patients with muscle-invasive urothelial carcinoma of the bladder (miUCB) preceding radical cystectomy (RC). MATERIALS AND METHODS: A prospective multisite phase II trial was conducted. Key eligibility criteria included: resectable miUCB (T2-T4a, N0, M0), and Eastern Cooperative Oncology Group performance status 0 to 1. Patients received oral Neo-D 100mg once daily for 28+/-7 days followed by RC 8 to 24 hours after the last dose. The primary end point was feasibility, defined as>=60% of patients with miUCB completing therapy without treatment-related dose limiting toxicity (DLT). Pre- and posttreatment tumor immunohistochemistry of phosphorylated SFK (pSFK), Ki-67, and cleaved caspase (Cas)-3 results were analyzed by paired t test. RESULTS: The study completed full accrual with enrollment of 25 patients of whom 23 were evaluable for feasibility. The study achieved its primary end point with 15 patients (65%) completing therapy without treatment-related DLTs. DLTs included: fatigue (n = 2), pulmonary embolism, abdominal pain, supraventricular tachycardia, enteric fistula, hematuria, and dyspnea (n = 1 each). At RC, 5 patients (23%) had=60 years, or age multiplied by 10. RESULTS: In young subjects, the DULCIS low cutoff levels resulted in half the recurrent events that would have occurred using the other criteria. In elderly patients, the DULCIS results were similar to those calculated for the two age adjusted criteria. The adoption of traditional VTE exclusion criteria would have led to positive results in the large majority of elderly subjects, without a significant reduction in the rate of recurrent event. CONCLUSION: The results confirm the usefulness of the cutoff levels used in DULCIS. PMID- 26362348 TI - Erratum. PMID- 26362349 TI - A pH-triggered delayed-release chronotherapeutic drug delivery system of aceclofenac for effective management of early morning symptoms of rheumatoid arthritis. AB - CONTEXT: Rheumatoid arthritis (RA) is differentiated as an early morning exacerbation of the core arthritis condition associated with increase in pain and stiffness in joints and necessitate for medication. OBJECTIVE: The aim of the present work was to develop and optimise a pH-triggered delayed-release colon specific aceclofenac microspheres and to accomplish chronotherapy of RA. METHODS: A 3-factor, 3-level Box-Behnken design (BBD) was used to optimise selected variables. Developed formulation was evaluated for in vivo delayed response and anti-arthritis activity in rats. RESULTS: The particle size and encapsulation efficacy of these microspheres were 117.36 +/- 10.54 um and 85.06 +/- 5.85%, respectively. Optimised formulation was analysed by SEM, DSC, X-RPD and FTIR. The in vivo evaluation revealed delayed anti-inflammatory activity in carrageenan induced rats and anti-arthritic activity in freund's adjuvant-induced arthritis rats. CONCLUSION: The optimised aceclofenac microspheres formulation is potential for the chronotherapy of early morning symptoms of RA. PMID- 26362350 TI - Potential external contamination of pneumatic seed drills during sowing of dressed maize seeds. AB - BACKGROUND: The use of pneumatic drills in maize cultivation causes dispersion in the atmosphere of some harmful substances normally used for dressing maize seeds. Some of the dust particles may be deposited on the machine's body, becoming dangerous for the environment and for operators. The aim of the present study was to analyse the amount of dust deposited on the frame of drills during maize sowing operations. Tests were performed with different drills and in different operating conditions. RESULTS: Data analysis showed that a significant amount (up to 30%) of the tracer can be deposited on the drill body. When wind was not present, higher quantities of tracer were collected and the forward speed did not influence significantly the tracer deposit on the seed drills. The use of different devices designed to prevent dust dispersion was able to limit up to 95% but was not able to eliminate the external contamination of the drill. CONCLUSION: The particles present on drills could become a problem for the operator during the filling of the drill. Additionally, the environment can be contaminated if pesticide remains on the drill, generating point-source pollution when the drill is parked outside. (c) 2015 Society of Chemical Industry. PMID- 26362351 TI - Disruption of phactr-1 pathway triggers pro-inflammatory and pro-atherogenic factors: New insights in atherosclerosis development. AB - Significant interest has recently emerged for phosphatase and actin regulatory protein (PHACTR1) gene in heart diseases prognosis. However, the functional role of phactr-1 protein remains elusive in heart related-diseases such as atherosclerosis, coronary artery calcification, ischaemic stroke, coronary artery stenosis and early-onset myocardial infarction. Phactr-1 is directly regulated by vascular endothelial growth factor A165 (VEGF-A165) through VEGF receptor 1 (VEGR 1) and Neuropilin-1 (NRP-1). Using an antagonist peptide approach to inhibit the interaction of VEGF-A165 to NRP-1 and VEGF-R1, we highlighted the importance of both cysteine residues located at the end of VEGF-A165 exon-7 and at the exon-8 to generate functional peptides, which decreased Phactr-1 expression. Here, we report original data showing Phactr-1 down-expression induces the expression of Matrix Metalloproteinase (MMP) regulators such as Tissue inhibitor of metalloproteinase (TIMP-1/-2) and Reversion-inducing-cysteine-rich protein with kazal motifs (RECK). Furthermore, focal adhesion kinases (FAK/PYK2/PAXILLIN) and metabolic stress (AMPK/CREB/eNOS) pathways were inhibited in endothelial cells. Moreover, the decrease of phactr-1 expression induced several factors implicated in atherosclerotic events such as oxidized low-density lipoprotein receptors (CD36, Clusterin, Cadherin-13), pro-inflammatory proteins including Thrombin, Thrombin receptor 1 (PAR-1), A Disintegrin And Metalloprotease domain-9/-17 (ADAM 9/-17), Trombospondin-2 and Galectin-3. Besides, Phactr-1 down-expression also induces emerging atherosclerosis biomarkers such as semicarbazide-sensitive amine oxidase (SSAO) and TGF-beta-inducible gene h3 (betaIG-H3). In this report, we show for the first time the direct evidence of the phactr-1 biological function in the regulation of pro-atherosclerotic molecules. This intriguing result strengthened heart diseases PHACTR-1 single-nucleotide polymorphisms (SNP) correlation. Taken together, our result highlighted the pivotal role of phactr-1 protein in the pathogenesis of atherosclerosis. PMID- 26362352 TI - The evidence for low-dose CT screening of lung cancer. AB - Lung cancer remains the leading cause of cancer-related death in the United States. An effective screening tool for early lung cancer detection has long been sought. Early chest radiograph and low-dose computed tomography (LDCT) screening trials were promising and demonstrated increased cancer detection. However, these studies were not able to improve lung cancer mortality. The National Lung Screening Trial resulted in decreased lung cancer mortality with LDCT screening in a high-risk population. Similar trials are currently underway in Europe. With LDCT now being widely implemented, it is paramount for radiologists to understand the evidence for lung cancer screening. PMID- 26362353 TI - Hemorrhagic fever with renal syndrome-related encephalopathy: magnetic resonance imaging findings. AB - OBJECTIVE: To report the incidence and findings of brain magnetic resonance imaging (MRI) in patients with hemorrhagic fever with renal syndrome (HFRS) related encephalopathy along with its clinical course. METHODS: Medical records and brain MRI were reviewed from January 2004 to January 2013. The final cohort consisted of 145 patients. Brain MRI findings were correlated with associated clinical stage of disease. RESULTS: The MRI findings associated with clinical course of HFRS-related encephalopathy were posterior reversible encephalopathy syndrome pattern (n=3) in oliguric phase and splenial lesion pattern (n=1) in febrile phase. CONCLUSIONS: Brain MRI findings in HFRS-related encephalopathy may be associated with the clinical course of HFRS. PMID- 26362354 TI - Diagnosis of adhesive capsulitis: comparison of contrast-enhanced MRI with noncontrast-enhanced MRI. AB - OBJECTIVE: To compare the diagnostic performance of contrast-enhanced (CE) magnetic resonance imaging (MRI) and non-CE MRI for adhesive capsulitis (AC). METHODS: CE MRI of 50 AC and 53 non-AC patients were reviewed by two radiologists independently. RESULTS: Axillary capsular thickening and T2 hyperintensity (sensitivity=92-94%; specificity=53-64%) and enhancement of the axillary capsule and rotator interval (sensitivity=92-98%; specificity=38-64%) were helpful in diagnosing AC. Interobserver reliability was highest with axillary joint capsule enhancement (kappa=0.92). CONCLUSION: Non-CE and CE MRI are helpful in confirming the clinical diagnosis of AC. CE-MRI may improve assessment of the rotator interval and diagnostic confidence in patients with AC. PMID- 26362356 TI - Measurement of gait speed in older adults to identify complications associated with frailty: A systematic review. AB - Several frailty screening tests in older cancer patients were developed but their statistical performance is low. We aimed to assess whether measurement of usual gait speed (GS) alone could be used as a frailty screening test in older cancer patients. This systematic review was conducted on "pub med" between 1984 and 2014 and included reviews and original studies. Eligibility criteria were: GS over a short distance, alone or included in composite walking tests (Timed Get Up and Go test: TGUG, Short Physical Performance Battery: SPPB) in older people (aged 65 and over) living in a community setting and predictive value of GS on medical complications associated with frailty. 46 articles were finally selected. GS alone is consensual and recommended for screening sarcopenia in elderly. A slow GS is predictive of early death, disability, falls and hospitalization/institutionalization in older people living in a community setting. GS alone is comparable to composite walking tests that do not provide additional information on the medical complications associated with frailty. Despite few studies in geriatric oncology, GS seems to predict overall survival and disability. We suggest GS over 4m (at a threshold of 1m/s) as a new frailty screening test in older cancer patients (65 and over) to guide the implementation of a comprehensive geriatric assessment during the initial management phase or during follow-up. Prospective cohort studies are needed to validate this algorithm and compare it with other screening tool. PMID- 26362355 TI - Symptoms, weight loss, and physical function in a lifestyle intervention study of older cancer survivors. AB - OBJECTIVES: Many older cancer survivors are overweight or obese, with additional illness burden increasing functional decline, which may affect their ability to engage in lifestyle interventions. This study examined how overweight long-term survivors' symptom severity associated with comorbidity prior to a diet and exercise intervention was associated with post-intervention function and examined symptoms' effects on function through change in physical activity, diet quality, and weight status. MATERIALS AND METHODS: This is a secondary data analysis of 514 breast, prostate, and colorectal cancer survivors who participated in the one year home-based diet and exercise intervention Reach-Out to Enhance Wellness trial. Measures included symptoms, weight, physical activity, diet quality, overall physical function (PF), and basic and advanced lower extremity function (BLEF and ALEF). Simple and serial mediation analyses were conducted to examine direct effects of symptom severity on PF, BLEF, and ALEF and indirect effects of symptom severity through changes in diet quality, physical activity, and weight. RESULTS: Symptom severity was directly associated with lower functioning scores for PF (b=-0.63 p<0.001), BLEF (b=-0.33, p<0.001), and ALEF (b=-0.22, p<0.001). Indirect effects of symptom severity through weight loss, physical activity, and diet were not significant. Weight loss and physical activity were associated with higher PF and ALEF and diet quality was associated with higher BLEF. CONCLUSION: Symptom severity of older, overweight cancer survivors negatively affects physical function. However, greater weight loss and more physical activity were associated with higher functioning scores, regardless of symptom severity. PMID- 26362357 TI - Chronic liver injury in mice promotes impairment of skin barrier function via tumor necrosis factor-alpha. AB - CONTEXT: Alcohol is frequently used to induce chronic liver injury in laboratory animals. Alcohol causes oxidative stress in the liver and increases the expression of inflammatory mediators that cause hepatocellular damage. However, during chronic liver injury, it is unclear if/how these liver-derived factors affect distal tissues, such as the skin. OBJECTIVE: The purpose of this study was to evaluate skin barrier function during chronic liver injury. MATERIALS AND METHODS: Hairless mice were administered 5% or 10% ethanol for 8 weeks, and damages to the liver and skin were assessed using histological and protein analysis methods, as well as by detecting inflammatory mediators in the plasma. RESULTS: After alcohol administration, the plasma concentration of the aspartate and alanine aminotransferases increased, while albumin levels decreased. In mice with alcohol-induced liver injury, transepidermal water loss was significantly increased, and skin hydration decreased concurrent with ceramide and type I collagen degradation. The plasma concentrations of [Formula: see text]/[Formula: see text] and tumor necrosis factor-alpha (TNF-alpha) were significantly increased in mice with induced liver injury. TNF receptor (TNFR) 2 expression was upregulated in the skin of alcohol-administered mice, while TNFR1 levels remained constant. Interestingly, the impairment of skin barrier function in mice administered with 10% ethanol was ameliorated by administering an anti-TNF-alpha antibody. CONCLUSIONS: We propose a novel mechanism whereby plasma TNF-alpha, via TNFR2 alone or with TNFR1, plays an important role in skin barrier function during chronic liver disease in these mouse models. PMID- 26362358 TI - The potential of synthetic indolylquinoline derivatives for Abeta aggregation reduction by chemical chaperone activity. AB - Alzheimer's disease (AD) is the most prevalent form of dementia associated with progressive cognitive decline and memory loss. Extracellular beta-amyloid (Abeta) is a major constituent of senile plaques, one of the pathological hallmarks of AD. Abeta deposition causes neuronal death via a number of possible mechanisms such as increasing oxidative stress. Therefore therapeutic approaches to identify novel Abeta aggregate reducers could be effective for AD treatment. Using a Trx His-Abeta biochemical assay, we screened 11 synthetic indolylquinoline compounds, and found NC009-1, -2, -6 and -7 displaying potential to reduce Abeta aggregation. Treating Tet-On Abeta-GFP 293 cells with these compounds reduced Abeta aggregation and reactive oxygen species. These compounds also promoted neurite outgrowth in Tet-On Abeta-GFP SH-SY5Y cells. Furthermore, treatment with above compounds improved neuronal cell viability, neurite outgrowth, and synaptophysin expression level in mouse hippocampal primary culture under oligomeric Abeta-induced cytotoxicity. Moreover, the tested NC009-1 significantly ameliorated Abeta-induced inhibition of hippocampal long-term potentiation in mouse hippocampal slices. Our results demonstrate how synthetic indolylquinoline compounds are likely to work as chemical chaperones in Abeta-aggregation reduction and neuroprotection, providing insight into the possible applications of indolylquinoline compounds in AD treatment. PMID- 26362359 TI - Long-term administration of the antidepressant vilazodone modulates rat brain monoaminergic systems. AB - Vilazodone has high affinity for the human 5-hydroxytryptamine1A (h5-HT1A) receptor and for the serotonin transporter (5-HTT). A previous in vivo microdialysis experiment showed that a single administration of vilazodone, dose dependently increases extracellular 5-HT but not norepinephrine (NE) or dopamine (DA) levels in rat medial prefrontal cortex and ventral hippocampus. The effects of vilazodone on monoaminergic systems were assessed using single-unit extracellular recordings and microiontophoresis in the rat brain. Following depletion of 5-HT with para-chlorophenylalanine methyl-ester hydrochloride (PCPA), vilazodone still suppressed neuronal firing of dorsal raphe nucleus (DRN) 5-HT neurons to a similar extent than controls, indicating that this inhibition is via 5-HT1A receptors activation. Following 2-day intraperitoneal administration of vilazodone (5 mg/kg/day), there was a significant decrease in 5 HT neuronal firing which recovered to baseline levels by day 14 of administration, likely due to 5-HT1A autoreceptor desensitization. Two- and 14 day administration of vilazodone decreased the mean firing and bursting activities of ventral tegmental area (VTA) DA neurons, while only its repeated administration significantly dampened the mean firing rate of locus coeruleus (LC) NE neurons. Vilazodone acted as an agonist at 5-HT1A receptors, while showing a 5-HTT blocking capacity when injected acutely. After repeated vilazodone regimen, while there was no change in sensitivity of 5-HT1A receptors, the enhancement in 5-HT transmission yielded an increase in the tonic activation of these receptors located in the hippocampus. PMID- 26362360 TI - Depressive-like behavior observed with a minimal loss of locus coeruleus (LC) neurons following administration of 6-hydroxydopamine is associated with electrophysiological changes and reversed with precursors of norepinephrine. AB - Depression is a common co-morbid condition most often observed in subjects with mild cognitive impairment (MCI) and during the early stages of Alzheimer's disease (AD). Dysfunction of the central noradrenergic nervous system is an important component in depression. In AD, locus coeruleus (LC) noradrenergic neurons are significantly reduced pathologically and the reduction of LC neurons is hypothesized to begin very early in the progression of the disorder; however, it is not known if dysfunction of the noradrenergic system due to early LC neuronal loss is involved in mediating depression in early AD. Therefore, the purpose of this study was to determine in an animal model if a loss of noradrenergic LC neurons results in depressive-like behavior. The LC noradrenergic neuronal population was reduced by the bilateral administration of the neurotoxin 6-hydroxydopamine (6-OHDA) directly into the LC. Forced swim test (FST) was performed three weeks after the administration of 6-OHDA (5, 10 and 14 MUg/MUl), animals administered the 5 MUg/MUl of 6-OHDA demonstrated a significant increase in immobility, indicating depressive-like behavior. This increase in immobility at the 5 MUg/MUl dose was observed with a minimal loss of LC noradrenergic neurons as compared to LC neuronal loss observed at 10 and 14 MUg/MUl dose. A significant positive correlation between the number of surviving LC neurons after 6-OHDA and FST immobile time was observed, suggesting that in animals with a minimal loss of LC neurons (or a greater number of surviving LC neurons) following 6-OHDA demonstrated depressive-like behavior. As the 6-OHDA induced loss of LC neurons is increased, the time spent immobile is reduced. Depressive-like behavior was also observed with the 5 MUg/MUl dose of 6-OHDA with a second behavior test, sucrose consumption. FST increased immobility following 6 OHDA (5 MUg/MUl) was reversed by the administration of a single dose of L-1-3-4 dihydroxyphenylalanine (DOPA) or l-threo-3,4-dihydroxyphenylserine (DOPS) prior to behavioral assessment. Surviving LC neurons 3 weeks after 6-OHDA (5 MUg/MUl) demonstrated compensatory changes of increased firing frequency, a more irregular firing pattern, and a higher percentage of cells firing in bursts. These results indicate that depressive-like behavior in mice is observed following the administration of 6-OHDA and the loss of LC noradrenergic neurons; however, the depressive-like behavior correlates positively with the number of surviving LC neurons with 6-OHDA administration. This data suggests the depression observed in MCI subjects and in the early stages of AD may due to the hypothesized early, minimal loss of LC neurons with remaining LC neurons being more active than normal. PMID- 26362362 TI - Mark Hanson: a developmental health pioneer. PMID- 26362361 TI - The new psychoactive substances 5-(2-aminopropyl)indole (5-IT) and 6-(2 aminopropyl)indole (6-IT) interact with monoamine transporters in brain tissue. AB - In recent years, use of psychoactive synthetic stimulants has grown rapidly. 5-(2 Aminopropyl)indole (5-IT) is a synthetic drug associated with a number of fatalities, that appears to be one of the newest 3,4 methylenedioxymethamphetamine (MDMA) replacements. Here, the monoamine-releasing properties of 5-IT, its structural isomer 6-(2-aminopropyl)indole (6-IT), and MDMA were compared using in vitro release assays at transporters for dopamine (DAT), norepinephrine (NET), and serotonin (SERT) in rat brain synaptosomes. In vivo pharmacology was assessed by locomotor activity and a functional observational battery (FOB) in mice. 5-IT and 6-IT were potent substrates at DAT, NET, and SERT. In contrast with the non-selective releasing properties of MDMA, 5 IT displayed greater potency for release at DAT over SERT, while 6-IT displayed greater potency for release at SERT over DAT. 5-IT produced locomotor stimulation and typical stimulant effects in the FOB similar to those produced by MDMA. Conversely, 6-IT increased behaviors associated with 5-HT toxicity. 5-IT likely has high abuse potential, which may be somewhat diminished by its slow onset of in vivo effects, whereas 6-IT may have low abuse liability, but enhanced risk for adverse effects. Results indicate that subtle differences in the chemical structure of transporter ligands can have profound effects on biological activity. The potent monoamine-releasing actions of 5-IT, coupled with its known inhibition of MAO A, could underlie its dangerous effects when administered alone, and in combination with other monoaminergic drugs or medications. Consequently, 5-IT and related compounds may pose substantial risk for abuse and serious adverse effects in human users. PMID- 26362364 TI - New insights into the variable effectiveness of levothyroxine monotherapy for hypothyroidism. PMID- 26362365 TI - Vascular Malformations and Their Treatment in the Growing Patient. AB - Vascular anomalies consisting of 2 groups of lesions, vascular tumors and vascular malformations, frequently arise in the head and neck and often occur in the pediatric age group. This classification is based on the differences in natural history, histologic features, and cellular turnover of the 2 groups. The management of these anomalies can be challenging, and evidence-based decisions about treatment are complicated by an inconsistency in the nomenclature for these lesions found in the literature. This article covers the clinical presentation, etiology, and pathophysiology and treatment approaches of the vascular anomalies in the pediatric population. PMID- 26362366 TI - Medication-related osteonecrosis of the jaw(MRONJ) that is linked to the treatment of malignant. Introduction. PMID- 26362367 TI - The Frequency of Medication-related Osteonecrosis of the Jaw and its Associated Risk Factors. AB - This article provides the best current frequency estimate of medication-related osteonecrosis of the jaws (MRONJ), and identifies factors associated with the risk of developing osteonecrosis of the jaw (ONJ) among patients exposed to relevant medications (ie, antiresorptive or antiangiogenic agents). MRONJ is a rare but serious complication of cancer treatment or osteoporosis management. This review confirms that antiresorptive medications such as oral or intravenous bisphosphonates and denosumab are the most common risk factors for developing ONJ. The risk of MRONJ is greater in patients with cancer than in those receiving antiresorptive treatments for osteoporosis by a factor of 10. PMID- 26362368 TI - Initial experience in hybrid PET-MRI for evaluation of refractory focal onset epilepsy. AB - PURPOSE: We aim to evaluate the utility/improved accuracy of hybrid PET/MR compared to current practice separate 3T MRI and PET-CT imaging for localization of seizure foci. METHOD: In a pilot study, twenty-nine patients undergoing epilepsy surgery evaluation were imaged using PET/MR. This subject group had 29 previous clinical 3T MRI as well as 12 PET-CT studies. Prior clinical PET and MR images were read sequentially while the hybrid PET/MR was concurrently read. RESULTS: The median interval between hybrid PET/MR and prior imaging studies was 5 months (range 1-77 months). In 24 patients, there was no change in the read between the clinical exams and hybrid PET/MR while new anatomical or functional lesions were identified by hybrid PET/MR in 5 patients without significant clinical change. Four new anatomical MR lesions were seen with concordant PET findings. The remaining patient revealed a new abnormal PET lesion without an MR abnormality. All new PET/MR lesions were clinically significant with concordant EEG and/or SPECT results as potential epileptic foci. CONCLUSION: Our initial hybrid PET-MRI experience increased diagnostic yields for detection of potential epileptic lesions. This may be due to the unique advantage of improved co registration and simultaneous review of both structural and functional data. PMID- 26362369 TI - A case of infant hot water epilepsy: A clinical commentary with video sequences. PMID- 26362370 TI - Genetic association study of the HLA class II alleles DRB1, DQA1, and DQB1 in patients with pharmacoresistant temporal lobe epilepsy associated with mesial hippocampal sclerosis. AB - PURPOSE: Temporal lobe epilepsy (TLE) is the most common variety of focal epilepsy among adults. The neuroinflammatory mechanisms of epilepsies may be involved in the genesis of seizures and refractory epilepsies, particularly in the case of progressive syndromes such as TLE associated with mesial hippocampal sclerosis (TLE-HS). The goal of the present study is investigate the genetic profile of susceptibility of individuals with TLE-HS by analyzing the possible association of TLE-HS with human leukocyte antigen (HLA) DRB1, DQA1 and DQB1 alleles. METHODS: Peripheral blood samples were collected from 42 individuals with pharmacoresistant TLE-HS and 89 healthy controls. The typing of the HLA class II alleles from DRB1, DQB1, and DQA1 loci were analyzed using sequence specific primer-polymerase chain reaction (SSP-PCR) and identified through sequencing. Statistical analysis of relative allele frequencies was performed using an Excel spreadsheet; p-value, relative risk (RR), and odds ratio (OR) were calculated using the software Epi Info 6.0. p-values <0.05 following Bonferroni's method correction were considered statistically significant. RESULTS: HLA DRB1*13:02 was the only allele with a statistically significant difference (p=0.01) in frequency between patients and controls. However, the significance was lost following Bonferroni's method correction (p=0.44). The remainder of the alleles in the HLA-DRB1, HLA-DQB1 and HLA-DQA1 regions did not exhibit any significant association. CONCLUSION: The allele HLA DRB1*13:02 has exhibited a tendency to behave as a susceptibility factor for TLE-HS. PMID- 26362371 TI - Familial epilepsy in Algeria: Clinical features and inheritance profiles. AB - PURPOSE: To document the clinical characteristics and inheritance pattern of epilepsy in multigeneration Algerian families. METHODS: Affected members from extended families with familial epilepsy were assessed at the University Hospital of Oran in Algeria. Available medical records, neurological examination, electroencephalography and imaging data were reviewed. The epilepsy type was classified according to the criteria of the International League Against Epilepsy and modes of inheritance were deduced from pedigree analysis. RESULTS: The study population included 40 probands; 23 male (57.5%) and 17 female subjects (42.5%). The mean age of seizure onset was 9.5 +/- 6.1 years. According to seizure onset, 16 patients (40%) had focal seizures and 20 (50%) had generalized seizures. Seizure control was achieved for two patients (5%) for 10 years, while 28 (70%) were seizure-free for 3 months. Eleven patients (27.5%) had prior febrile seizures, 12 were diagnosed with psychiatric disorders and four families had syndromic epilepsy. The consanguinity rate among parents of affected was 50% with phenotypic concordance observed in 25 families (62.5%). Pedigree analysis suggested autosomal dominant (AD) inheritance with or without reduced penetrance in 18 families (45%), probable autosomal recessive (AR) inheritance in 14 families (35%), and an X-linked recessive inheritance in one family. CONCLUSION: This study reveals large Algerian families with multigenerational inheritance of epilepsy. Molecular testing such as exome sequencing would clarify the genetic basis of epilepsy in some of our families. PMID- 26362372 TI - COL4A1 gene mutation--beyond a vascular syndrome. PMID- 26362373 TI - Early electroencephalography in patients with Emergency Room diagnoses of suspected new-onset seizures: Diagnostic yield and impact on clinical decision making. AB - PURPOSE: To assess the utility of acute electroencephalography (EEG) performed in the emergency room (ER) and its impact on subsequent management of patients with new-onset seizures. Adults who recover fully in the ER following suspected isolated new-onset seizures are usually discharged to the neurology clinic for further review. An EEG at that stage may be normal. We sought to assess the feasibility and yield of early EEG in the ER setting, its impact on management. METHODS: A prospective study from January 2008 to January 2011 of patients diagnosed by ER physicians with uncomplicated suspected first episodes of unprovoked convulsive seizures. All patients underwent routine 30-min EEG in the ER prior to discharge and specialist review was arranged in the epilepsy clinic within 2 weeks of presentation. Management decisions were at the discretion of the treating neurologist. Seizure recurrence was assessed during a follow up period between 9 months and 3 years. RESULTS: 136 patients were included in the study (92 males). Mean age was 32 years (range 16-73). Forty had abnormal EEGs: 16 focal epileptiform discharges, 12 focal slowing, 10 generalized spike-wave discharges and 2 generalized slowing. Using multivariate analysis, those with abnormal EEG (51% vs 11%, p = 0.003) and abnormal MRI (53% vs 28%, p < 0.001) were more likely to be commenced on anticonvulsant therapy. Abnormal MRI (p = 0.001) was independently associated with a higher risk of recurrence. CONCLUSIONS: Following an ER diagnosis of new-onset uncomplicated seizure, early EEG had a high diagnostic yield. Abnormal EEG and abnormal MRI significantly contributed to decision-making regarding treatment at specialist review. Abnormal MRI was associated with significantly higher risks of subsequent seizures. PMID- 26362374 TI - Choice of the first anti-epileptic drug in elderly patients with newly diagnosed epilepsy: A Finnish retrospective study. AB - PURPOSE: The choice of initial anti-epileptic drug (AED) for elderly and younger adult patients with newly diagnosed epilepsy was assessed. METHODS: The pattern of initial prescription of AEDs between 2000 and 2013 was retrospectively studied in two community-dwelling cohorts, identified from the case records of Kuopio University Hospital (KUH): elderly subjects (aged 65 or above at the time of diagnosis; n = 529) and a random sample of younger adults (16-64 years old at the time of diagnosis; n = 201). Furthermore, nationwide register data from the Social Insurance Institution of Finland were included in the analysis, from the years 2004 and 2012. RESULTS: Valproic acid (VPA) and carbamazepine (CBZ) were the most common initial AEDs both among the elderly (49% and 31% of prescriptions, respectively) and for the patients in the younger-adults group (19% and 61%, respectively) in the KUH data. In the nationwide register data, the most frequently used initial AEDs for the elderly were VPA and oxcarbazepine. The selection of VPA was associated with higher age (P < 0.001), myocardial infarction (P = 0.003), and stroke (P = 0.013). Lower probability of receiving CBZ was observed with more advanced age (P < 0.001) and myocardial infarction (P = 0.002), whereas diabetes (P = 0.018) and atrial fibrillation (P = 0.045) predicted a higher probability. CONCLUSION: First-generation AEDs are still the most commonly employed first drugs for elderly patients with newly diagnosed epilepsy in Finland. Age and comorbid conditions have an effect in the choice of the initial AED treatment. PMID- 26362376 TI - Lidocaine for status epilepticus in adults. AB - INTRODUCTION: Our goal was to perform a systematic review of the literature on the use of intravenous lidocaine in adults for status epilepticus (SE) and refractory status epilepticus (RSE) to determine its impact on seizure control. METHODS: All articles from MEDLINE, BIOSIS, EMBASE, Global Health, HealthStar, Scopus, Cochrane Library, the International Clinical Trials Registry Platform (inception to November 2014), and gray literature were searched. The strength of evidence was adjudicated using both the Oxford and GRADE methodology by two independent reviewers. RESULTS: Overall, 13 studies were identified, with 11 manuscripts and 2 meeting abstracts. Seventy-six adult patients were treated for 82 episodes of SE/RSE. Patients had varying numbers of anti-epileptic drugs (AEDs), 1-12, on board prior to lidocaine therapy. During 69 of the 82 (84.1%) episodes of SE/RSE, phenytoin was on board. The dose regimen of lidocaine varied, with some utilizing bolus dosing alone; others utilizing a combination of bolus and infusion therapy. Overall, 70.7% of seizures responded to lidocaine, with complete cessation and greater than 50% reduction seen in 64.1% and 6.1% respectively. Patient outcomes were sparingly reported. CONCLUSIONS: There currently exists level 4, GRADE C evidence to support the consideration of lidocaine for SE and RSE in the adult population. Thus there is currently weak evidence to support the use of lidocaine in this context. Further prospective studies of lidocaine administration in this setting are warranted. PMID- 26362375 TI - Subiculum-entorhinal cortex interactions during in vitro ictogenesis. AB - PURPOSE: Our aim was to establish the contribution of neuronal networks located in the entorhinal cortex (EC) and subiculum to the generation of interictal and ictal onset patterns recorded in vitro. METHODS: We employed field potential recordings of epileptiform activity in rat brain slices induced with the application of the K(+) channel blocker 4-aminopyridine. Local connections between the EC and subiculum were severed to understand how EC-subicular circuits contribute to patterns of epileptiform synchronization. RESULTS: First, we found that ictal discharges occurred synchronously in these two structures, initiating from either the EC or subiculum, and were characterized by low voltage fast (LVF) or sudden onsets. Second, sudden onset ictal events initiated more frequently in the EC, whereas LVF onset ictal discharges appeared more likely to initiate in the subiculum (P<0.001). In both structures, polyspike interictal discharges occurred in brain slices generating sudden onset ictal events while isolated slow interictal discharges were recorded in experiments characterized by LVF onset ictal activity. Third, severing the connections between subiculum and EC desynchronized both interictal and ictal discharges occurring in these two regions, leading to a significant decrease in ictal duration (regardless of the onset type) along with blockade of polyspike interictal activity in subiculum. CONCLUSIONS: These findings highlight the contribution of EC-subicular interactions to epileptiform synchronization and, specifically, to ictogenesis in this in vitro model. PMID- 26362377 TI - The adverse event profile of levetiracetam: A meta-analysis on children and adults. AB - PURPOSE: To analyze the adverse events (AEs) significantly associated with levetiracetam (LEV) therapy through a meta-analysis of all available double blind, randomized placebo-controlled trials (RCTs), performed in any age, gender, ethnic background and disease. General tolerability and study withdrawals due to AEs associated with LEV treatment were also investigated. In addition, a dose effect responses relationship for all variables was assessed. METHODS: RCTs were identified searching Medline (PubMed), Embase and Cochrane CENTRAL for the words "Levetiracetam" and "randomized controlled trial", with different search strategies, setting the limits "humans" and "English". Very common and common AEs according to the summary of product characteristics were investigated. RevMan version 5.2 was used for the statistical analyses. Risk difference with 95% confidence intervals was used to investigate the association of any AEs and withdrawal with LEV. RESULTS: Twenty-six studies with 2832 patients were included in the RCTs analysis. Nasopharyngitis, somnolence, dizziness, nervousness/irritability and asthenia/fatigue were statistically significant associated with LEV. In addition, LEV was significantly associated with an increased risk of AEs-related withdrawals. No dose-response relationship was found for any of the assessed variables. CONCLUSIONS: This first large meta analysis suggests that participants were more likely to discontinue LEV than placebo. The AE profile confirmed that LEV is associated with few unfavorable sedative, vestibulocerebellar and behavioral effects, such as nervousness and irritability. However, there does not seem to be a clear dose-response relationship. PMID- 26362378 TI - Diagnostic criteria currently proposed for "ictal epileptic headache": Perspectives on strengths, weaknesses and pitfalls. AB - PURPOSE: When we published the diagnostic criteria for "ictal epileptic headache" in 2012, we deliberately and consciously chose to adopt restrictive criteria that probably underestimate the phenomenon, rather than spread panic among patients and physicians who are reluctant to accept this entity. METHODS: Here we discuss four intriguing clinical cases to highlight why we believe, to this day, that it is necessary to follow these restrictive diagnostic criteria. CONCLUSIONS: EEG is not recommended as a routine examination for children diagnosed with headache, but it is mandatory and must be carried out promptly in cases of prolonged headache that does not respond to antimigraine drugs, if epilepsy is suspected or has been diagnosed previously. This is not a marginal or irrelevant question because possible isolated, non-motor, ictal manifestations should be taken into account before declaring that an epileptic patient is "seizure free" so as to ensure that any decision taken to suspend anticonvulsant therapy is safe. PMID- 26362379 TI - Neurophysiological and clinical findings on Nodding Syndrome in 21 South Sudanese children and a review of the literature. AB - PURPOSE: To describe the neurophysiological and clinical features of Nodding Syndrome (NS) in South Sudan. METHODS: The study was performed at the Epilepsy Service of "Usratuna" sited in Juba, South Sudan. The clinical history of each subject was collected along with an EEG tracing. RESULTS: Twenty-one children (10 females) were diagnosed with NS. Fifteen (72%) children were classified as Probable NS and six (28%) as Confirmed NS. They ranged in age between 6 and 14 years, and age at seizure onset ranged from 5 to 12 years. All the subjects presented with intellectual disability which was mild in severity in 12 (57%) cases, moderate in seven (33%) cases and severe in two (10%) cases. Interictal EEG was abnormal in 20 subjects. In 18 (85%) subjects, the EEG showed 2-3.5 Hz spike-and-wave discharges often intermingled with sharp waves. Intermittent light stimulation was normal. In 12 (57%) children, interictal abnormalities were activated by hyperventilation. Ictal EEG was obtained in three patients. In all ictal EEGs head nodding episodes came in clusters during hyperventilation. None of the patients achieved good seizure control even if all of them received antiepileptic treatment (carbamazepine alone [43%] or in association with phenobarbitone or phenytoin). CONCLUSION: This study confirms that NS is an encephalopathy and intellectual disabilities are partially independent of seizure frequency and EEG pathological activity. Based on interictal and ictal EEG patterns and on the experience of other researchers, valproic acid would seem to be the first-choice antiepileptic drug. NS in South Sudan presents with clinical and neurophysiological features which are similar to those described in northern Uganda and more severe than in Tanzania. PMID- 26362381 TI - The role of sleep electroencephalography in patients with new onset epilepsy. AB - PURPOSE: An increased propensity for seizures is associated with different stages of the sleep-wake cycle. In this study, we prospectively analyzed patients with new-onset epilepsy and investigated the clinical correlates of the yield obtained from sleep electroencephalography (EEG) recordings in patients with a normal wakefulness EEG. METHODS: All patients admitted to our epilepsy unit due to unprovoked epileptic seizures and not yet treated with antiepileptic drugs were recruited consecutively for the last three years. All had a routine EEG at wakefulness (WEEG), and those with no epileptiform activity had a video-EEG recording during sleep (SEEG). RESULTS: We investigated a total of 241 patients; 129 patients (53.5%) had both wakefulness and sleep EEG recordings. The patients with abnormal WEEG were older than those with normal WEEG (p = 0.005). Abnormal WEEG was detected in only 31.2% of patients with focal seizures, but in 77.3% of patients with generalized seizures (p < 0.001). WEEG was abnormal in 44.0% of patients with diurnal seizures, but in 27.5% of nocturnal seizures (p = 0.007). Abnormal WEEG was present in 75.5% of patients with a presumed genetic origin and in 59.3% of patients with structural etiology (p < 0.001). Sleep EEG detected an abnormality in 41.8% of patients with normal WEEG; of these, 82.8% were focal abnormalities. In contrast, the majority of abnormalities detected in WEEG were generalized (55.8%, p < 0.001). CONCLUSION: Our results showed a greater likelihood of abnormal WEEG in older patients and in those with generalized epilepsy, diurnally precipitating seizures, and epilepsy of presumed genetic origin. PMID- 26362382 TI - Seizure-triggered Takotsubo syndrome rarely causes SUDEP. AB - Since almost 20 y it is known that seizures may trigger Takotsubo syndrome (TTS). Since then it has been repeatedly proposed that TTS could be the cause of sudden unexpected death in epilepsy (SUDEP). A review of the so far reported cases of seizure-triggered TTS was carried out to see how often seizure-triggered TTS is fatal. Altogether 59 papers were identified which reported altogether 74 patients with seizure-triggered TTS. Age was reported in 70 patients and ranged from 18 to 82 y. Gender was reported in 70 cases and was female in 60 cases (86%). The type of triggering seizure was reported in 47 cases. In 28 patients (60%) the trigger was a generalized tonic clonic seizure, in 15 cases (32%) a generalized status epilepticus, and in 3 cases a complex partial seizure. The outcome was mentioned in 63 of the 74 patients. Full recovery was reported in 61 cases (97%), incomplete recovery in none of the patients, and a fatal outcome in 2 patients (3%). Fatalities are rare in patients experiencing seizure-triggered TTS. This is why seizure-triggered TTS does not seem to play a major role in the pathogenesis of SUDEP. PMID- 26362380 TI - Efficacy and safety of lacosamide as first add-on or later adjunctive treatment for uncontrolled partial-onset seizures: A multicentre open-label trial. AB - PURPOSE: To evaluate the efficacy and safety of lacosamide administered as either first add-on or later add-on antiepileptic drug (AED) therapy for patients with uncontrolled partial-onset seizures (POS). METHODS: In this open-label, multicentre trial, patients with POS initiated oral lacosamide (titrated to 400 mg/day) either as add-on to first AED monotherapy, or as later add-on to 1-3 concomitant AEDs after >= 2 previous AEDs. The primary efficacy variable was the proportion of patients achieving seizure freedom for the first 12 weeks of the 24 week Maintenance Phase. RESULTS: 456 patients received >= 1 dose of lacosamide (96 as first add-on, 360 as later add-on). In the first add-on cohort, 27/72 (37.5%) patients completed 12 weeks treatment and remained seizure-free; 18/68 (26.5%) remained seizure-free after 24 weeks. 64/91 (70.3%) patients achieved >= 50% reduction in seizure frequency during maintenance treatment. This was accompanied by a mean 7.1 +/- 16.00 point improvement from Baseline in the Quality of Life Inventory in Epilepsy (QOLIE-31-P) total score for 24-week completers, with improvement reported in all subscales. Most common treatment emergent adverse events (TEAEs) were dizziness (31.3%) and headache (13.5%). In the later add-on cohort, 39/261 (14.9%) and 29/249 (11.6%) patients remained seizure-free after completing 12 and 24 weeks' treatment, respectively. 178/353 (50.4%) patients achieved >= 50% reduction in seizure frequency during maintenance treatment. Mean change in QOLIE-31-P total score was 4.8 +/- 14.74 points among 24-week completers. Common TEAEs were dizziness (33.6%), somnolence (15.0%) and headache (11.4%). CONCLUSIONS: Lacosamide initiated as first add-on treatment was efficacious and well tolerated in patients with uncontrolled POS. PMID- 26362383 TI - Temporal current-source of spikes suggests initial treatment failure in childhood absence epilepsy. AB - PURPOSE: In addition to the frontal lobe, the temporal lobe may also be involved in typical absence seizures. However, few studies have addressed the relationship between this involvement and drug responsiveness in childhood absence epilepsy (CAE). In this study, we observed the current-source distribution (CSD) of generalized spike-and-wave discharges (GSWDs) and investigated the relationship between temporal lobe involvement in the CSD and responsiveness to initial antiepileptic drug (AED) in CAE. METHOD: Seventeen consecutive patients with CAE were retrospectively enrolled in the study. Patients were divided into an initial response group and an initial-failure group, according to their responsiveness to the initial AED treatment. For each patient, the spike peak CSD of an averaged GSWD was obtained from the initial electroencephalogram. We compared the incidence of temporal involvement in the CSD between the two groups. We also compared clinical variables, including age of onset, gender, type and dose of first AED, time to cessation of clinical seizures, and seizure-free status. RESULTS: The initial-response and initial-failure groups contained 12 and five patients, respectively. Temporal lobe involvement was more frequent (80% vs. 17%, p = 0.03), and time to cessation of clinical seizures was more prolonged (median 2.5 months vs. 8 months, p<0.01) in the initial-failure than in the initial response group. None of the other variables studied differed between groups. CONCLUSION: Initial AED failure was associated with temporal involvement in the CSD of CAE patients. This electrophysiological information may be helpful in clinical practice by estimating the efficacy of initial AED treatment in AED naive CAE patients in advance. PMID- 26362384 TI - Cost of status epilepticus in a tertiary care hospital in India. AB - PURPOSE: Status epilepticus (SE) is one of the most important neurological emergencies. The present study evaluated both direct cost of SE and predictors of cost in an Indian tertiary care teaching hospital in Lucknow India. METHODS: SE was defined as continuous seizure for >= 5 min or recurrent seizures without regaining consciousness. Etiologies of SE were categorized as acute central nervous system (CNS) pathology, acute non-CNS pathology, chronic CNS pathology, congenital disorders and others. Patients requiring mechanical ventilation (MV) received ventilators free of cost. Mortality and disability on discharge were noted. RESULTS: Fifty-five patients aged 8-90 years were included (males, 33). Fifty (89.3%) patients had generalized convulsive SE. The severity of SE as assessed by Status Epilepticus Scoring Scale was unfavorable (score, 3-6) in 41 (74.5%) patients. The etiology of SE was categorized as acute CNS pathology in 28 (51%) patients, non-CNS and chronic CNS pathology in 11 (19.6%) patients each, remote congenital pathology in 2 (3.6%), and others in 3 (5.6%). Thirty (53.6%) patients had comorbidities. Median duration of hospitalization was 7 (range, 1 72) days.Twenty six patients were hospitalized for >7 days. SE was controlled by 2 drugs in 47 (85.5%) patients and refractory to 2 intravenous antiepileptic drugs in 8 (14.5%). Nineteen (34.5%) patients died, and 29 (51.8%) showed favorable outcomes on discharge. Median hospital expenditure per case was INR 19,900 ($309.87; range, INR 1600-574,000). On multivariate analysis, SE hospitalization costs were determined by refractoriness of SE and mechanical ventilation (MV). Hospitalization cost of SE was lower than those of stroke. CONCLUSION: Acute non-CNS pathology is largely responsible for the high cost of SE, particularly refractory SE requiring mechanical ventilation. PMID- 26362385 TI - Systematic review of the efficacy in seizure control and safety of neuronavigation in epilepsy surgery: The need for well-designed prospective studies. AB - PURPOSE: To evaluate the efficacy of surgery with neuronavigation compared to conventional neurosurgical treatment of epilepsy in terms of safety and seizure outcomes and to assess the quality of the evidence base of neuronavigation in this clinical context. METHOD: Systematic review using the electronic databases of Cochrane, CRD, PubMed, Embase, SciELO and LILACS in Portuguese, English and Spanish. The [MeSH] terms included "epilepsy" and "neuronavigation". ELIGIBILITY CRITERIA: Studies assessing surgery with neuronavigation for the surgical treatment of epilepsy or brain injuries associated with epileptic seizures. RESULTS: We identified 28 original articles. All articles yielded scientific evidence of low quality. Outcome data presented in the articles identified was heterogeneous and did not amount to compelling evidence that epilepsy surgery with neuronavigation produces higher rates of seizure control, a reduced need for reoperations, or lower rates of complications or postoperative neurological deficits. CONCLUSION: We were unable to find any publications providing convincing evidence that neuronavigation improves outcomes of epilepsy surgery. Whilst this does not mean that neuronavigation cannot improve neurosurgical outcomes in this clinical setting, well-designed research studies evaluating the role of neuronavigation are urgently needed. PMID- 26362386 TI - Repackaged sodium valproate tablets--Meeting quality and adherence to ensure seizure control. AB - PURPOSE: Sodium valproate, which is commonly repacked to assist with adherence to ensure seizure control, is hygroscopic and therefore sensitive to moisture. The aim of this study was thus to determine the stability implications of removing the enteric coated tablets from their original packaging and repackaging into a Dose Administration Aid (DAA) with storage under various environmental conditions. METHODS: Physicochemical stability of enteric coated sodium valproate tablets repackaged into a DAA and stored at controlled room temperature, accelerated and refrigerated conditions was evaluated for 28 days. A validated high performance liquid chromatography method was used for the quantitation of the drug content. RESULTS: Although the chemical stability (sodium valproate between 95 and 105% of labelled content) was maintained for 28 days for all storage conditions, for those tablets stored under accelerated conditions the integrity of the enteric coat was compromised after only 8 days. CONCLUSIONS: Repackaging of enteric coated sodium valproate should be undertaken with caution and be informed by storage climate. This is particularly relevant for those patients living in hot, humid environments where they should be advised to store their DAA in a refrigerator. PMID- 26362387 TI - Bitemporal epilepsy: A specific anatomo-electro-clinical phenotype in the temporal lobe epilepsy spectrum. AB - PURPOSE: Temporal lobe epilepsy (TLE) with bilateral ictal involvement (bitemporal epilepsy, BTLE) is an intriguing form of TLE whose characteristics need to be carefully identified as BTLE patients are not good surgical candidates. The purpose of this study was to define the anatomo-electro-clinical features differentiating BTLE from unilateral TLE (UTLE). METHODS: Forty-eight BTLE patients underwent long-term video-EEG monitoring (VEEG) and experienced seizures with bilateral temporal lobe involvement. Their main electro-clinical (demographics, interictal and ictal EEG, ictal signs) and neuro-imaging [brain magnetic resonance imaging (MRI)] data were compared with those of a group of 38 UTLE patients. RESULTS: In comparison with the UTLE patients, the BTLE cohort was significantly older at the time of epilepsy onset (p = 0.023), more frequently experienced bilateral asynchronous interictal epileptiform discharges during wakefulness (p = 0.001) and sleep (p < 0.001), bilateral upper limb dystonia (p = 0.005), and auditory auras (p = 0.027), and less frequently showed a recognisable initial ictal EEG pattern of focal flattening or low-voltage fast activity (p < 0.001), post-ictal memory of seizures (p = 0.001), staring (p < 0.001), head deviation (p = 0.004), oro-alimentary automatisms (p = 0.006), and positive brain MRI (p < 0.001). MRI revealed neoplastic lesions (p = 0.007) or alterations other than hippocampal sclerosis (p = 0.028) only in the UTLE patients. CONCLUSION: The possibility of recognising BTLE patients during pre-surgical evaluation or being able to suspect bitemporal seizures before VEEG by identifying particular anatomo electro-clinical patterns is diagnostically important for epileptologists and can help to prevent possible surgical failures. PMID- 26362388 TI - Familial temporal lobe epilepsy due to focal cortical dysplasia type IIIa. AB - PURPOSE: Focal cortical dysplasia (FCD) represents a common cause of refractory epilepsy. It is considered a sporadic disorder, but its occasional familial occurrence suggests the involvement of genetic mechanisms. METHODS: Siblings with intractable epilepsy were referred for epilepsy surgery evaluation. Both patients were examined using video-EEG monitoring, MRI examination and PET imaging. They underwent left anteromedial temporal lobe resection. RESULTS: Electroclinical features pointed to left temporal lobe epilepsy and MRI examination revealed typical signs of left-sided hippocampal sclerosis and increased white matter signal intensity in the left temporal pole. PET examination confirmed interictal hypometabolism in the left temporal lobe. Histopathological examination of resected tissue demonstrated the presence FCD type IIIa, i.e. hippocampal sclerosis and focal cortical dysplasia in the left temporal pole. CONCLUSION: We present a unique case of refractory mesial temporal lobe epilepsy in siblings, characterized by an identical clinical profile and histopathology of FCD type IIIa, who were successfully treated by epilepsy surgery. The presence of such a high concordance between the clinical and morphological data, together with the occurrence of epilepsy and febrile seizures in three generations of the family pedigree points towards a possible genetic nature of the observed FCD type IIIa. PMID- 26362389 TI - A systematic review of suggestive seizure induction for the diagnosis of psychogenic nonepileptic seizures. AB - Suggestive seizure induction is a widely used method for diagnosing psychogenic nonepileptic seizures (PNES). Despite seven decades of multidisciplinary research, however, there is still no unified protocol, no definitive agreement on the ethical framework and no consensus on diagnostic utility. This systematic review surveys the evidence at hand and addresses clinically relevant aspects of suggestive seizure induction. In addition to its use for facilitating the diagnostic process, its mechanism of action and utility in elucidating the psychopathology of PNES will be discussed. PMID- 26362391 TI - Transient global amnesia with a hippocampal lesion followed by transient epileptic amnesia. PMID- 26362390 TI - Blockade of endothelin B receptor improves the efficacy of levetiracetam in chronic epileptic rats. AB - PURPOSE: To elucidate the mechanisms that regulate p-glycoprotein (PGP) expression and function in pharmacoresistant epilepsy, we investigated the effect of an ETB receptor antagonist (BQ788) and a p38 mitogen-activated protein kinase (p38MAPK) inhibitor (SB202190) on intractable seizures in chronic epileptic rats. METHODS: Lithium-pilocarpine-induced chronic epileptic rats were used in the present study. Animals were given levetiracetam (LEV), LEV + SB202190, LEV + BQ788, SB202190 or BQ788 over a 3-day period using an osmotic pump. Seizure activity was recorded by video-EEG monitoring with 2h of recording per day at the same time of day. We also performed western blot after EEG analysis. RESULTS: Compared to control animals, PGP, ETB receptor and p38MAPK expression was increased in the hippocampus of epileptic animals. Neither SB202190 nor BQ788 affected the spontaneous seizure activity in epileptic rats. Three of ten rats were responders and achieved complete seizure control or significant reduction in seizure activity by LEV. In four of ten rats, seizure frequency was unaltered by LEV (non-responders). LEV + SB202190 reduced seizure duration, but not seizure frequency, in both responders and non-responders. LEV + BQ788 alleviated seizure frequency and seizure duration in both responders and non-responders. Compared to responders, PGP and ETB receptor expression was enhanced in the hippocampus of non-responders. CONCLUSION: To the best of our knowledge, these findings are the first indications of the role of ETB receptor in pharmacoresistant epilepsy. Therefore, the present data suggest that the regulation of the ETB receptor mediated signaling pathway may be important for identification of new therapeutic strategies for improving antiepileptic drug efficacy. PMID- 26362392 TI - Semiological and psychiatric characteristics of children with psychogenic nonepileptic seizures: Gender-related differences. AB - PURPOSE: To compare semiological characteristics, precipitating stress factors and psychiatric diagnoses of girls and boys with psychogenic nonepileptic seizures (PNESs). METHODS: We retrospectively reviewed medical records of children diagnosed with PNES and who also underwent psychiatric evaluation. Sixty two children (44 girls, 18 boys), aged 11-18 years (mean age 14.19 +/- 1.96 years) were included. Diagnosis of PNES was established by any of the following: (1) observation of the seizure by a neurologist and routine EEG, (2) evaluation of amateur video records of the typical seizure and routine EEG, or (3) video-EEG monitoring. Psychiatric examinations of patients were performed using the Schedule for Affective Disorders and Schizophrenia for School Age Children Present and Lifetime Version (KSADS-PL). RESULTS: Tremor was the most prevalent ictal motor sign in both girls and boys. Atonic falls and longer episodes were significantly more frequent in girls than boys. Tonic-clonic-like movements of the extremities were significantly more prevalent in boys than girls. No gender specific differences were observed in the rates of semiological types. Academic underachievement was the most prevalent precipitating stressor for boys, and was significantly more prevalent in boys than girls. The rate of major depression was significantly higher in girls than boys. The most prominent diagnosis in boys was attention deficit/hyperactivity disorder, and this was significantly more prevalent than in girls. CONCLUSION: PNES in males of juvenile age may be a distinct entity from that in girls with different semiological and psychogenic correlates. Consideration of these gender-related differences may be beneficial for the early recognition and treatment of PNES. PMID- 26362393 TI - Relationship between mono-hydroxy-carbazepine serum concentrations and adverse effects in patients on oxcarbazepine monotherapy. AB - PURPOSE: To evaluate the relationship between serum concentrations of mono hydroxy-carbazepine (MHD), the main metabolite of oxcarbazepine (OXC), and the occurrence of adverse effects (AE) in a large group of patients on OXC monotherapy. METHODS: An antiepileptic drug (AED) therapeutic drug monitoring (TDM) database was analyzed especially with regard to OXC dosage, MHD serum concentration, and the occurrence of AE. In total, 893 blood samples of 442 patients were included in this retrospective study. The statistical evaluation was performed by means of Kaplan-Meier estimates, log-rank tests and generalized estimating equations (GEE). RESULTS: At least one AE was reported in 78 (17.6%) of the 442 patients. At MHD serum concentrations of 30.0 MUg/ml and 43.7 MUg/ml and OXC dosages of 33.1 mg/kg and 62.3 mg/kg, 25% and 75% of patients, respectively, experienced at least one AE. Log-rank tests indicated that younger patients (<18 years) may be able to tolerate higher MHD serum levels (p = 0.006) and higher OXC dosages per body weight (p < 0.001) compared to adult patients (>= 18 years). Furthermore, AEs occurred at higher body-weight adjusted OXC dosages of extended release formulations compared to immediate-release formulations (p = 0.010), whereas MHD serum levels at which AEs occurred did not differ significantly between formulations (p = 0.125). Multivariate GEE confirmed the results. CONCLUSION: The occurrence of AEs is significantly (and non-linearly) dependent on MHD serum level, whereas the dependence of OXC dosage is less distinctive. But, tolerability of OXC seems to depend on age of the patients as well as on pharmaceutical formulation of OXC. PMID- 26362394 TI - Thyroid hormones: Possible roles in epilepsy pathology. AB - Thyroid hormones (THs) L-thyroxine and L-triiodothyronine, primarily known as metabolism regulators, are tyrosine-derived hormones produced by the thyroid gland. They play an essential role in normal central nervous system development and physiological function. By binding to nuclear receptors and modulating gene expression, THs influence neuronal migration, differentiation, myelination, synaptogenesis and neurogenesis in developing and adult brains. Any uncorrected THs supply deficiency in early life may result in irreversible neurological and motor deficits. The development and function of GABAergic neurons as well as glutamatergic transmission are also affected by THs. Though the underlying molecular mechanisms still remain unknown, the effects of THs on inhibitory and excitatory neurons may affect brain seizure activity. The enduring predisposition of the brain to generate epileptic seizures leads to a complex chronic brain disorder known as epilepsy. Pathologically, epilepsy may be accompanied by mitochondrial dysfunction, oxidative stress and eventually dysregulation of excitatory glutamatergic and inhibitory GABAergic neurotransmission. Based on the latest evidence on the association between THs and epilepsy, we hypothesize that THs abnormalities may contribute to the pathogenesis of epilepsy. We also review gender differences and the presumed underlying mechanisms through which TH abnormalities may affect epilepsy here. PMID- 26362395 TI - Peripheral administration of palmitoylated prolactin-releasing peptide induces Fos expression in hypothalamic neurons involved in energy homeostasis in NMRI male mice. AB - Energy homeostasis is the result of a balance between energy intake and expenditure, and the hypothalamus plays a key role in the regulation of these processes. The hypothalamic prolactin-releasing peptide (PrRP) is involved in food intake regulation and energy homeostasis, although only its lipidized analogs exert central anorexigenic effects after peripheral administration. The aim of the present study was to delineate the extent of the Fos expression as a marker of neuronal activation within the hypothalamic structures involved in food intake regulation after peripherally administered palmitoylated PrRP31 (palm PrRP31) and to determine whether the anorexigenic effect of peripherally administered palm-PrRP31 influence the activity of hypocretin (HCRT) and oxytocin (OXY) neurons, i.e., the neuropeptides crucially involved in the regulation of energy homeostasis. The data confirmed an anorexigenic effect of palm-PrRP31 treatment (5mg/kg, s.c.) in mice. In the palm-PrRP31-treated animals, a significant increase in Fos expression was observed in the hypothalamic paraventricular (PVN), dorsomedial (DMN), and arcuate (Arc) nuclei and in the neurons of the nucleus of the solitary tract (NTS). Moreover, significant Fos expression was observed in the lateral hypothalamic area (LHA) HCRT neurons and PVN OXY neurons after palm-PrRP31 administration. The present findings may indicate that palm-PrRP31 may be involved in energy homeostasis via the activation of several hypothalamic structures. Fos activation of the hypothalamic OXY and HCRT neurons in the PVN and LHA emphasizes the importance of the areas mentioned in the central action of palm-PrRP31. PMID- 26362396 TI - Advance care planning in cystic fibrosis: Current practices, challenges, and opportunities. AB - BACKGROUND: Studies in cystic fibrosis (CF) report late attention to advance care planning (ACP). The purpose of this study was to examine ACP with patients receiving care at US adult CF care programs. METHODS: Chart abstraction was used to examine ACP with adults with CF dying from respiratory failure between 2011 and 2013. RESULTS: We reviewed 210 deaths among 67 CF care programs. Median age at death was 29 years (range 18-73). Median FEV1 in the year preceding death was 33% predicted (range 13-100%); 68% had severe lung disease with FEV1<40% predicted. ACP was documented for 129 (61%), often during hospitalization (61%). Those with ACP had earlier documentation of treatment preferences, before the last month of life (73% v. 35%; p=<0.01). Advance directives were completed by 93% of those with ACP versus 75% without (p<0.01); DNR orders and health care proxy designation occurred more often for those with ACP. Patients awaiting lung transplant had similar rates of ACP as those who were not (67% v. 61%; p=0.55). The frequency of ACP varied significantly among the 29 programs contributing data from four or more deaths. CONCLUSIONS: ACP in CF often occurs late in the disease course. Important decisions default to surrogates when opportunities for ACP are missed. Provision of ACP varies significantly among adult CF care programs. Careful evaluation of opportunities to enhance ACP and implementation of recommended approaches may lead to better practices in this important aspect of CF care. PMID- 26362397 TI - CF healthcare workers feel unprepared in providing suitable end of life care and desire more education: Results of a nationwide survey. AB - INTRODUCTION: Little is known about the depth of knowledge and preparedness of CF caregivers in delivering end of life and palliative care to CF patients and families. METHOD: Nationwide survey questionnaires for CF care providers using the CF Foundation Listserv electronic web-based tool. RESULTS: The majority of non-physician CF care providers (55%) had more than 15 years of experience in their discipline and 84% of physician had greater than 15 years of experience. The majority reported that they felt "somewhat" or "very" involved in palliative or end of life care in their current role. Yet, when asked whether they felt adequately prepared to deliver palliative and end of life care, only 18% reported that they were "fully prepared" and 45% felt that they were only "minimally" or "not" prepared. Further, only one third of respondents received more than 10h of education in general palliative or end-of-life care, while only 10% had received more than 10h of education specific to CF end of life care. The majority (73%) of CF healthcare providers preferred more education specific to CF end of life care. CONCLUSION: CF healthcare providers are involved in CF end of life issues but a fair number did not understand their role and felt inadequately prepared in delivering suitable end of life and palliative care. Many desired more education in the provision of such care. PMID- 26362398 TI - Magnetic resonance-transcranial ultrasound fusion imaging: A novel tool for brain electrode location. AB - BACKGROUND: A combination of preoperative magnetic resonance imaging (MRI) with real-time transcranial ultrasound, known as fusion imaging, may improve postoperative control of deep brain stimulation (DBS) electrode location. Fusion imaging, however, employs a weak magnetic field for tracking the position of the ultrasound transducer and the patient's head. Here we assessed its feasibility, safety, and clinical relevance in patients with DBS. METHODS: Eighteen imaging sessions were conducted in 15 patients (7 women; aged 52.4 +/- 14.4 y) with DBS of subthalamic nucleus (n = 6), globus pallidus interna (n = 5), ventro intermediate (n = 3), or anterior (n = 1) thalamic nucleus and clinically suspected lead displacement. Minimum distance between DBS generator and magnetic field transmitter was kept at 65 cm. The pre-implantation MRI dataset was loaded into the ultrasound system for the fusion imaging examination. The DBS lead position was rated using validated criteria. Generator DBS parameters and neurological state of patients were monitored. RESULTS: Magnetic resonance ultrasound fusion imaging and volume navigation were feasible in all cases and provided with real-time imaging capabilities of DBS lead and its location within the superimposed magnetic resonance images. Of 35 assessed lead locations, 30 were rated optimal, three suboptimal, and two displaced. In two cases, electrodes were re-implanted after confirming their inappropriate location on computed tomography (CT) scan. No influence of fusion imaging on clinical state of patients, or on DBS implantable pulse generator function, was found. CONCLUSIONS: Magnetic resonance-ultrasound real-time fusion imaging of DBS electrodes is safe with distinct precautions and improves assessment of electrode location. It may lower the need for repeated CT or MRI scans in DBS patients. PMID- 26362399 TI - Dclk1+ small intestinal epithelial tuft cells display the hallmarks of quiescence and self-renewal. AB - To date, no discrete genetic signature has been defined for isolated Dclk1+ tuft cells within the small intestine. Furthermore, recent reports on the functional significance of Dclk1+ cells in the small intestine have been inconsistent. These cells have been proposed to be fully differentiated cells, reserve stem cells, and tumor stem cells. In order to elucidate the potential function of Dclk1+ cells, we FACS-sorted Dclk1+ cells from mouse small intestinal epithelium using transgenic mice expressing YFP under the control of the Dclk1 promoter (Dclk1 CreER;Rosa26-YFP). Analysis of sorted YFP+ cells demonstrated marked enrichment (~6000 fold) for Dclk1 mRNA compared with YFP- cells. Dclk1+ population display ~6 fold enrichment for the putative quiescent stem cell marker Bmi1. We observed significantly greater expression of pluripotency genes, pro-survival genes, and quiescence markers in the Dclk1+ population. A significant increase in self renewal capability (14-fold) was observed in in vitro isolated Dclk1+ cells. The unique genetic report presented in this manuscript suggests that Dclk1+ cells may maintain quiescence, pluripotency, and metabolic activity for survival/longevity. Functionally, these reserve characteristics manifest in vitro, with Dclk1+ cells exhibiting greater ability to self-renew. These findings indicate that quiescent stem-like functionality is a feature of Dclk1-expressing tuft cells. PMID- 26362402 TI - Monitoring of biogenic amines and drugs of various therapeutic groups in urine samples with use of HPLC. AB - A high-performance liquid chromatography method for simultaneous separation and determination of biogenic amines [dopamine, epinephrine, serotonin and its six metabolites (normetanephrine, metanephrine, 3,4-dihydroxyphenylacetic acid, 4 hydroxy-3-methoxyphenylglycol, homovanilic acid and 5-hydroxyindoloacetic acid)] with drugs from different therapeutically groups [analgesics (paracetamol, metamizol), diuretics (furosemide) and antibiotics (cefazolin, fluconazole)] was developed. A chromatographic column with pre-column with octadecylsilane phase (C18e ) and two detectors - diode array serial connected and fluorescence - was used. Gradient elution of mixture of acetate buffer (pH 4.66) and methanol as a mobile phase was applied. The limit of detection (LOD) of 8-10 ng/mL and limit of quantitation (LOQ) of 24-30 ng/mL for biogenic amines, as well as the LOD of 50 100 ng/mL and the LOQ of 150-300 ng/mL for drugs, were determined. The applied sample preparation method allowed recoveries of 93% for the biogenic amines and 92% for the drugs to be achieved. The developed procedure has been applied to simultaneous determination of the examined compounds in urine samples and could be used in clinical analysis. PMID- 26362401 TI - Interferon-regulatory factor-1 (IRF1) regulates bevacizumab induced autophagy. AB - PURPOSE: Antiangiogenic therapy is commonly being used for the treatment of glioblastoma. However, the benefits of angiogenesis inhibitors are typically transient and resistance often develops. Determining the mechanism of treatment failure of the VEGF monoclonal antibody bevacizumab for malignant glioma would provide insight into approaches to overcome therapeutic resistance. EXPERIMENTAL DESIGN: In this study, we evaluated the effects of bevacizumab on the autophagy of glioma cells and determined target genes involving in the regulation of bevacizumab-induced autophagy. RESULTS: We demonstrated that bevacizumab treatment increased expression of autophagy markers and autophagosome formation in cell culture experiments as well as in in vivo studies. Gene expression profile analysis performed on murine xenograft models of glioblastoma showed increased transcriptional levels of STAT1/IRF1 signaling in bevacizumab resistant tumors compared to control tumors. In vitro experiments showed that bevacizumab treatment increased IRF1 expression in a dose and time dependent manner, which was coincident with bevacizumab-mediated autophagy. Down regulation of IRF1 by shRNA blocked autophagy and increased AIF-dependent apoptosis in bevacizumab treated glioma cells. Consistently, IRF1 depletion increased the efficacy of anti VEGF therapy in a glioma xenograft model, which was due to less bevacizumab promoted autophagy and increased apoptosis in tumors with down-regulated IRF1. CONCLUSIONS: These data suggest that IRF1 may regulate bevacizumab-induced autophagy, and may be one important mediator of glioblastoma resistant to bevacizumab. PMID- 26362404 TI - Trends in the Average Age of Quitting Among U.S. Adult Cigarette Smokers. AB - INTRODUCTION: Quitting smoking at any age confers health benefits. However, studies have suggested that quitting by age 35 years leads to mortality rates similar to never smokers. This study assessed whether the mean and median ages of past-year quitting and prevalence of past-year quit attempts and successful quitting by age group changed over time. METHODS: Data came from 113,599 adult cigarette smokers participating in the 1997-2012 National Health Interview Survey, an annual, cross-sectional household survey of U.S. adults aged >=18 years. Mean and median ages of past-year successful abstinence (quit 6-12 months) were computed. Orthogonal polynomial logistic regression models tested for trends in quit attempts and successful quitting. Data were analyzed in 2014. RESULTS: The average age of quitting (40.0 years in 1997-1998, 39.5 years in 2011-2012, p=0.80) and median age of quitting (35.9 years in 1997-1998, 36.9 years in 2011 2012, p=0.62) did not change over time. During 1997-2012, the percentage of smokers making a past-year quit attempt increased among those aged 25-34, 35-44, and 45-64 years; the percentage of smokers who reported quitting successfully increased among those aged 25-34 and 35-44 years (p<0.001). CONCLUSIONS: Although the average age of quitting did not change over time, increases in past-year quit attempts and successful quitting occurred among adults aged 25-44 years. Proven population-level interventions--including price increases, mass media campaigns, comprehensive smoke-free policies, and health systems interventions--should be continued to further increase cessation, particularly among younger adults. PMID- 26362403 TI - The Development of the Recovery Assessments by Phone Points (RAPP): A Mobile Phone App for Postoperative Recovery Monitoring and Assessment. AB - BACKGROUND: In Sweden, day surgery is performed in almost 2 million patients per year. Patient satisfaction is closely related to potential adverse events during the recovery process. A way to empower patients and give them the opportunity to affect care delivery is to let them evaluate their recovery process. The most common evaluation method is a follow-up telephone call by a nurse one or two days after surgery. In recent years, mHealth apps have been used to evaluate the nurse patient relationship for self-management in chronic diseases or to evaluate pain after surgery. To the best of our knowledge, no previous research has explored the recovery process after day surgery via mobile phone in a Swedish cohort. OBJECTIVE: The objective of the study is to describe the process of developing a mobile phone app using a Swedish Web-based Quality of Recovery (SwQoR) questionnaire to evaluate postoperative recovery after day surgery. METHODS: The development process included five steps: (1) setting up an interdisciplinary task force, (2) evaluating the potential needs of app users, (3) developing the Swedish Web version of a QoR questionnaire, (4) constructing a mobile phone app, and (5) evaluating the interface and design by staff working in a day-surgery department and patients undergoing day surgery. A task force including specialists in information and communication technology, eHealth, and nursing care worked closely together to develop a Web-based app. Modifications to the QoR questionnaire were inspired by instruments used in the field of recovery for both children and adults. The Web-based app, Recovery Assessment by Phone Points (RAPP) consists of two parts: (1) a mobile app installed on the patient's private mobile phone, and (2) an administrator interface for the researchers. RESULTS: The final version of the SwQoR questionnaire, which includes 31 items, was successfully installed in RAPP. The interface and the design were evaluated by asking for user opinions about the design and usefulness of the app with 10 day surgery patients. Some minor adjustments were made concerning text size and screen color. CONCLUSIONS: Taking advantage of joint expertise, a useable Web based app adaptable to different technical platforms was constructed. In addition, the SwQoR was successfully transferred into digital format for use on mobile phones. PMID- 26362400 TI - Progresses towards safe and efficient gene therapy vectors. AB - The emergence of genetic engineering at the beginning of the 1970's opened the era of biomedical technologies, which aims to improve human health using genetic manipulation techniques in a clinical context. Gene therapy represents an innovating and appealing strategy for treatment of human diseases, which utilizes vehicles or vectors for delivering therapeutic genes into the patients' body. However, a few past unsuccessful events that negatively marked the beginning of gene therapy resulted in the need for further studies regarding the design and biology of gene therapy vectors, so that this innovating treatment approach can successfully move from bench to bedside. In this paper, we review the major gene delivery vectors and recent improvements made in their design meant to overcome the issues that commonly arise with the use of gene therapy vectors. At the end of the manuscript, we summarized the main advantages and disadvantages of common gene therapy vectors and we discuss possible future directions for potential therapeutic vectors. PMID- 26362405 TI - Outreach for Annual Colorectal Cancer Screening: A Budget Impact Analysis for Community Health Centers. AB - INTRODUCTION: Fecal immunochemical testing (FIT) is an attractive approach for colorectal cancer screening at community health centers. This budget impact analysis investigated benefits and costs of FIT outreach-with FIT kits mailed to patients, followed by reminders and phone calls-compared with point-of-care (POC) strategies. METHODS: Five screening and cost outcomes were simulated over 1 year at a "base case" community health center serving 1000 screening-eligible patients: (1) FIT completion among patients due for screening; (2) proportion up to-date on screening; (3) cost per patient due for screening; (4) cost per completed FIT; and (5) total organizational cost. Uncertainty analysis investigated potential savings from optimizing staff workflows during FIT outreach. Data were collected in 2012-2014, with analysis conducted 2014-2015. RESULTS: Using POC strategies, 24.0% of patients due for screening completed FIT, versus 42.4% under outreach (18.4% absolute difference). When calculations included patients up-to-date on screening from prior colonoscopy, 41.7% were up to-date via POC, versus 55.8% for outreach (14.1% absolute difference). POC cost $4.93 per patient, versus $30.43 for outreach ($25.50 difference). Cost per patient screened was $20.60 for POC and $71.84 for outreach ($51.24 difference). Total organizational cost was $3,779 for POC distribution and $23,315 for outreach ($19,536 difference). Outreach costs decreased by approximately one fourth under optimized workflows. CONCLUSIONS: Outreach is an effective, practical, relatively low-cost strategy; costs could be reduced further by optimizing staff workflows. Despite its value, outreach costs more than POC distribution and may be difficult for community health centers to implement under current payment models. PMID- 26362406 TI - Face-to-face Information and Emotional Support from Trained Nurses Reduce Pain During Screening Mammography: Results from a Randomized Controlled Trial. AB - Pain and discomfort during breast examination can affect a woman's adherence to breast cancer-screening programs. The aim of this study was to determine whether a nursing intervention protocol that provides verbal information and support to women could reduce pain during mammography. A randomized controlled trial of 436 Spanish women aged 50-69 who attended a breast-screening program was performed. The experimental group received a customized nursing intervention that provided face-to-face information and emotional support during the examination. Pain and anxiety were measured using a visual analogue scale and the State-Trait Anxiety Inventory, respectively. Data regarding several potential confounders were also collected. The adjusted means of pain level in the study group were obtained from multiple linear regressions, and the adjusted odds ratios (OR) and 95% confidence intervals (CI) were obtained via logistic regression. After the intervention, the level of pain was significantly lower (p = .03) in the experimental group (0.98 +/- 2.28) compared with the group treated with normal care (1.48 +/- 2.29). Consequently, the probability of feeling pain during mammography was lower among women in the experimental group (OR = 0.44; 95% CI: 0.24-0.81). The intervention was more effective among women with the highest anxiety levels (OR = 0.33; 95% CI: 0.11-0.98), who did not expect pain (OR = 0.28; 95% CI: 0.08-0.97), and who did not fear the outcome of the mammography (OR = 0.18; 95% CI: 0.04-0.85). Providing verbal information, as well as supporting the women during the test, is a simple and achievable intervention for nurses and can help to reduce pain during screening mammography. PMID- 26362407 TI - Destabilization of the dimer interface is a common consequence of diverse ALS associated mutations in metal free SOD1. AB - Neurotoxic misfolding of Cu, Zn-superoxide dismutase (SOD1) is implicated in causing amyotrophic lateral sclerosis, a devastating and incurable neurodegenerative disease. Disease-linked mutations in SOD1 have been proposed to promote misfolding and aggregation by decreasing protein stability and increasing the proportion of less folded forms of the protein. Here we report direct measurement of the thermodynamic effects of chemically and structurally diverse mutations on the stability of the dimer interface for metal free (apo) SOD1 using isothermal titration calorimetry and size exclusion chromatography. Remarkably, all mutations studied, even ones distant from the dimer interface, decrease interface stability, and increase the population of monomeric SOD1. We interpret the thermodynamic data to mean that substantial structural perturbations accompany dimer dissociation, resulting in the formation of poorly packed and malleable dissociated monomers. These findings provide key information for understanding the mechanisms and energetics underlying normal maturation of SOD1, as well as toxic SOD1 misfolding pathways associated with disease. Furthermore, accurate prediction of protein-protein association remains very difficult, especially when large structural changes are involved in the process, and our findings provide a quantitative set of data for such cases, to improve modelling of protein association. PMID- 26362408 TI - [Vascular myeloproliferative neoplasm with normal cell blood count: Exploration and medical management]. AB - Negative BCR ABL myeloproliferative neoplasm (MPN) such as polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (MFP) are clonal hematological malignancies and may lead to a high risk of venous, arterial or microcirculatory thrombosis. Atypical sites of thrombosis can sometimes reveal the neoplasm disorder. Their diagnoses are a major issue because of the propensity to develop acute myeloid leukemia and/or myelofibrosis. The acquired JAK2V617F variant (Janus kinase 2; 9p24) is a prevalent MPN and also a sensitive marker for PV diagnosis (95% positive mutation), but not specific since found in approximately 50% of patients with ET and MFP. PATIENT AND METHODS: We present a diagnostic and a therapeutic approach based on one patient with microcirculatory ischemic manifestations in the toes, and who had strictly normal cell blood counts and was positive for JAK2V617F mutation: thrombotic risk factor evaluation; bone marrow biopsy; red cell adhesion assays. These experimental assays are promising for the development of new therapeutics in MPN; they assess red cell adherence to the vascular endothelium after the phosphorylation of Lu/BCAM subsequent to a positive JAK2V617F mutation. RESULTS: Compared with controls, our patient exhibited increased Lu/BCAM receptor phosphorylation and red blood cell adhesion. CONCLUSION: This development may lead to improved care for patients with thrombotic manifestations, normal blood cell counts, and a positive JAK2V617F mutation: multidisciplinary management, including regular hematological monitoring, could lead to the introduction of a cytoreductive treatment. PMID- 26362409 TI - Anti-inflammatory effects of linezolid on carrageenan-induced paw edema in rats. AB - The immunomodulatory activity of linezolid has recently been reported using in vitro experimental models. However, the anti-inflammatory activity of linezolid has not yet been demonstrated using in vivo experimental models. Therefore, the aim of the present study was to demonstrate the anti-inflammatory activity of linezolid and other anti-MRSA agents using the carrageenan-induced rat paw edema model. The pretreatment with 50 mg/kg linezolid significantly suppressed edema rates, compared with control (5% glucose), with edema rates at 0.5 and 3 h after the administration of carrageenan being 17.3 +/- 3.5 and 30.8 +/- 3.0%, respectively. On the other hand, edema rates were not suppressed by the pretreatments with 50 mg/kg vancomycin, teicoplanin, arbekacin, and daptomycin. Furthermore, we demonstrated that linezolid exhibited anti-inflammatory activity in a concentration-dependent manner. These effects were observed at linezolid concentrations that are achievable in human serum with conventional dosing. In conclusion, the results of the present study suggest that the anti-inflammatory activities of linezolid, in addition to its antimicrobial effects, have a protective effect against destructive inflammatory responses in areas of inflammation. PMID- 26362411 TI - Association of the bradykinin receptors genes variants with hypertension: a case control study and meta-analysis. AB - BACKGROUND: The present study was to investigate the role of bradykinin receptors genes polymorphisms on hypertension risk in Northern Han Chinese population. We also carried out a meta-analysis on Chinese to derive a more full assessment of this association. METHODS AND RESULTS: A total of 976 subjects from Northern Han Chinese and 7 studies with 1599 cases and 1425 controls were included in this case-control study and in the current meta-analysis, respectively. For the case control study, we identified the genotypes of -58T/C and 1098A/G polymorphism in BDKRB2 and BDKRB1 genes, respectively, by TaqMan PCR method. Overall, we found significant association between the -58T/C polymorphism and the increased risk of hypertension in the allele comparison (p = 0.01, OR = 1.386, 95% CI [1.138 1.688]). Subgroup analysis by gender suggested that this obvious association could still be found in males, but not in females. For the 1098A/G polymorphism, no significant association was revealed in overall and subgroup analysis. For the meta-analysis involving the -58T/C polymorphism, a significant association between this polymorphism and hypertension was observed in the whole group. In Chinese Han subgroup, we found significant association with hypertension in allele comparison(C vs. T: p = 0.03, OR = 1.28, 95% CI 1.03-1.59, pheterogeneity = 0.05). CONCLUSIONS: Our case-control study indicated that -58T/C might be significantly associated with the increased risk of hypertension in Northern Han Chinese population, which was partially confirmed by our meta-analysis. PMID- 26362410 TI - Cell and matrix response of temporomandibular cartilage to mechanical loading. AB - OBJECTIVES: The generation of transgenic mice expressing green fluorescent proteins (GFPs) has greatly aided our understanding of the development of connective tissues such as bone and cartilage. Perturbation of a biological system such as the temporomandibular joint (TMJ) within its adaptive remodeling capacity is particularly useful in analyzing cellular lineage progression. The objectives of this study were to determine: (i) if GFP reporters expressed in the TMJ indicate the different stages of cell maturation in fibrocartilage and (ii) how mechanical loading affects cellular response in different regions of the cartilage. DESIGN/METHODS: Four-week-old transgenic mice harboring combinations of fluorescent reporters (Dkk3-eGFP, Col1a1(3.6 kb)-GFPcyan, Col1a1(3.6 kb) GFPtpz, Col2a1-GFPcyan, and Col10a1-RFPcherry) were used to analyze the expression pattern of transgenes in the mandibular condylar cartilage (MCC). To study the effect of TMJ loading, animals were subjected to forced mouth opening with custom springs exerting 50 g force for 1 h/day for 5 days. Dynamic mineralization and cellular proliferation (EdU-labeling) were assessed in loaded vs control mice. RESULTS: Dkk3 expression was seen in the superficial zone of the MCC, followed by Col1 in the cartilage zone, Col2 in the prehypertrophic zone, and Col10 in the hypertrophic zone at and below the tidemark. TMJ loading increased expression of the GFP reporters and EdU-labeling of cells in the cartilage, resulting in a thickness increase of all layers of the cartilage. In addition, mineral apposition increased resulting in Col10 expression by unmineralized cells above the tidemark. CONCLUSION: The TMJ responded to static loading by forming thicker cartilage through adaptive remodeling. PMID- 26362412 TI - Heterologous gshF gene expression in various vector systems in Escherichia coli for enhanced glutathione production. AB - Glutathione (GSH), an important bioactive product, is widely used in production of pharmaceuticals and foods. In this study, four different vector systems, pET28a, pUC18, pUC19-P32, and pUC19-Pabb, were applied for expression of gshF, encoding the bifunctional glutathione synthetase of Streptococcus thermophiles. These four constructs were named as pET28a-gshF, pUC18-gshF, pUC19-P32-gshF and pUC19-Pabb-gshF, respectively, and then introduced into Escherichia coli strain BL21(DE3) for further investigation of protein expression and GSH production. The expression levels of the GshF in BL21(pUC19-P32-gshF) and BL21(pUC19-Pabb-gshF) were much lower than those of BL21(pET28a-gshF) and BL21(pUC18-gshF). In the fed batch fermentation, the GSH accumulated by BL21(pUC18-gshF) reached 15.21 g/L, which was the highest level of GSH biosynthesis ever reported. Although BL21(pUC19-Pabb-gshF) produced less GSH compared to BL21(pUC18-gshF), the final GSH concentration produced by BL21 (pUC19-Pabb-gshF) still accumulated to 5.09 g/L, which indicated the potential application of the constitutive promoter in GSH production. PMID- 26362413 TI - Manipulating pyruvate to acetyl-CoA conversion in Escherichia coli for anaerobic succinate biosynthesis from glucose with the yield close to the stoichiometric maximum. AB - Efficient succinate production in Escherichia coli is attained during anaerobic glucose fermentation in biosynthetic processes combining the reductive branch of the TCA cycle and the glyoxylate bypass. Pyruvate dehydrogenase (PDH) or pyruvate formate lyase (PFL) serves in E. coli as a source of acetyl-CoA, a substrate for the glyoxylate bypass. Depending on enzymes responsible for acetyl-CoA generation, the contribution of the glyoxylate bypass to the anaerobic succinate biosynthesis may vary to support redox balance resulting in diverse maximum achievable yield values. Anaerobic succinate biosynthesis from glucose was studied using E. coli strains with altered expression of genes encoding PFL and PDH. For acetyl-CoA formation by PFL, the yield of 1.32 mol succinate per mole of glucose was achieved with the theoretical value of 1.6 mol/mol. Involvement of PDH in anaerobic acetyl-CoA synthesis increased succinate yield up to 1.49 mol/mol, which is 89.8% of the predicted maximum (1.6(6) mol/mol). The maximum yield of 1.69 mol succinate per mol glucose, amounting to 98.8% of the stoichiometric maximum (1.71 mol/mol), was achieved with the strain possessing PDH as the primary anaerobic source of acetyl-CoA. During high cell density fermentation, the best engineered strain produced high amounts of succinate (570.7 mM) and only small quantities of acetate (11.9 mM). PMID- 26362414 TI - Television viewing and fatty liver in early midlife. The Cardiovascular Risk in Young Finns Study. AB - INTRODUCTION: Both sedentary behaviour and fatty liver are associated with increased risk of obesity and non-communicable diseases, but their relationship remains unknown. We investigated the relationship of television (TV) viewing time with serum gamma-glutamyltransferase (GGT) and Fatty Liver Index (FLI), and ultrasonographically assessed liver fat. METHODS: A total of 1,367 adults of the population-based Cardiovascular Risk in Young Finns study (748 women, 619 men, aged 34-49 years) had fasting serum GGT, triglycerides, weight, height, and waist circumference, and self-reported TV time data from 2001, 2007, and 2011. Changes in GGT and FLI, and liver ultrasound images in 2011 were studied in groups with constantly low (<= 1 h/d), moderate (1-3 h/d), or high (>= 3 h/d) daily TV time, and in groups with >= 1 hour increase/decrease in daily TV time between 2001 and 2011. RESULTS: Constantly high TV time was associated with higher GGT and FLI (P < 0.02 in both), and 2.3-fold (95% CI 1.2-4.5) increased risk of fatty liver regardless of age, sex, leisure-time and occupational physical activity, energy intake, diet composition, alcohol use, sleep duration, socioeconomic status, and smoking. Adjustment for BMI partly attenuated the associations. CONCLUSIONS: High TV viewing increases fatty liver risk. It may be one mechanism linking sedentary behaviour with increased cardiometabolic disease risks. PMID- 26362415 TI - Eosinophilic pustular folliculitis associated with hematological disorders: A report of two cases and review of Japanese literature. AB - Eosinophilic pustular folliculitis (EPF) occurs in patients with hematological disorders. However, clinical information about hematological disorder-associated EPF is scarce. We report two cases of EPF associated with mantle cell lymphoma and reviewed the available published work on Japanese cases. We identified a total of 23 Japanese cases, including the two cases reported here, who had hematological disorder-associated EPF. Fourteen cases were associated with treatment for hematological malignancies (transplantation-related EPF) and nine cases were associated with hematological malignancies themselves (hematological malignancy-related EPF). Although the skin eruption was clinically indistinguishable between the two subtypes, transplantation-related EPF occurred on the face and trunk of young and middle-aged men and women, whereas hematological malignancy-related EPF occurred mostly on the face of older men. Peripheral blood eosinophilia was more frequently observed in transplantation related EPF. These observations suggest variations among patients with EPF associated with hematological disorders. PMID- 26362416 TI - Haemostatic management for oral surgery in patients supported with left ventricular assist device--a preliminary retrospective study. AB - We investigated haemostatic management, frequency of postoperative bleeding, and prognosis of patients who had left ventricular assist devices, and who were having oral surgical procedures between April 2002 and March 2014, to identify risk factors for bleeding and find out which were the best methods of haemostasis. Medical records were examined retrospectively and we recorded details of the patients, and frequency of bleeding together with factors associated with it. Twenty-nine patients had 39 oral operations, and there were 17 bleeds (44%). The first procedure for each patient was used for statistical calculations. Duration of bleeding tended to be longer for patients with implantable devices (median (interquartile range, IQR) 12.0 (3-18) days) than for those with extracorporeal devices (median (IQR) 3.0 (1-4) days; p=0.079). There was a significantly greater difference in prothrombin time-international normalised ratio (PT-INR) before and after operation in patients who bled, whose median (range) was 0.85 (0.2-1.81), than in those who did not (median (IQR) 0.16 (-0.09-0.31) (p=0.015). There were moderate correlations with postoperative bleeding were seen for the difference between preoperative and postoperative PT INR (r=0.479, p=0.012) and PT-INR value when bleeding (r=0.407, p=0.035). In conclusion, postoperative bleeding occurred after oral operations in 17/29 patients with left ventricular assist devices by a median (IQR) of 0.85 (0.2 1.81) of the preoperative value. PMID- 26362417 TI - Pep19 drives epitope spreading in periodontitis and periodontitis-associated autoimmune diseases. AB - BACKGROUND AND OBJECTIVE: Epitope spreading is one of valid mechanisms operating in immunopathological processes of infection-induced autoimmune diseases. We hypothesized that the peptide 19 from Porphyromonas gingivalis heat shock protein (HSP) 60 (Pep19) may be the dominant epitope from which epitope-specific immune response to subdominant epitopes may diversify sequentially into autoimmune responses directed at human neoepitopes in P. gingivalis-induced periodontitis and autoimmune diseases. However, the exact feature and mechanism on how Pep19 may drive epitope spreading into human autoantigens in chronic periodontitis or P. gingivalis-induced experimental periodontitis has not been clarified. The present study was performed with the following specific aims: (i) to delineate retrospectively the features of epitope spreading by human cross-sectional analysis; (ii) to demonstrate prospectively the epitope spreading into new antigenic determinants in an ordered, predictable and sequential manner in experimental periodontitis; and (iii) to clarify the mechanism on how immunization with Pep19 may mobilize helper T cells or elicit B-cell responses to human autoantigens and neoantigen. MATERIAL AND METHODS: The study was devised for two independent investigations - a cross-sectional analysis on clinical subjects and a prospective analysis on experimental periodontitis - each being subdivided further into two additional independent observations. Cross-sectional dot immunoblot pattern against a panel of peptides of P. gingivalis HSP60 and human HSP60 was performed among age-dependent healthy subjects and between healthy subjects, patients with chronic periodontitis and patients with autoimmune disease, to identify epitope spreading. A peptide-specific T-cell line was established for phenotype analysis and for proliferation assay to an array of identical peptides. An identical prospective analysis was performed in P. gingivalis-induced experimental periodontitis or in Pep19-immunized mice. Cross reactivity of anti-Pep19 monoclonal antibody was also investigated. RESULTS: A dominant immune response exclusively to Pep19 prevailed in healthy human subjects (before the age of 40) and mice that persisted in chronic periodontitis and autoimmune diseases without being replaced further by subsequent subdominant epitopes. A sequential epitope spreading provoked by Pep19 to subdominant autoantigen peptide 19 from human HSP60 (Hu19) in most healthy human subjects and mice, and to autoantigen peptide 9 from human HSP60 (Hu9) and neoantigen oxidized low-density lipoprotein (ox-LDL) in P. gingivalis-induced chronic periodontitis and autoimmune diseases could be demonstrated in a reproducible and predictable manner. T-cell proliferative activity to multiple autoantigens Hu19, Hu9 and ox LDL, and cross-reactivity of anti-Pep19 monoclonal antibody to these epitopes may be proposed as cellular and molecular mechanisms responsible for the phenomenon. Moreover, the predictive value of Pep19 for Hu9 increased remarkably in the disease group when compared with that of the healthy group. CONCLUSION: Taken together, epitope spreading to Hu19, Hu9 and ox-LDL provoked by Pep19 could be proposed as a solid phenomenon observed in P. gingivalis-induced chronic periodontitis and infection-induced autoimmune diseases in a reproducible and predictable manner. T-cell proliferative activity to these peptides and cross reactivity of anti-Pep19 antibodies to multiple human autoantigens could be proposed as cellular and molecular mechanisms responsible for this phenomenon. PMID- 26362418 TI - Association between nutritional status and subjective health status in chronically ill children attending special schools. AB - PURPOSE: In hospitalized children with a chronic disease, malnutrition was associated with a lower subjective health status. In outpatient children with a chronic disease attending special schools, this association has never been studied. The aim of this study was to assess the association between nutritional status and subjective health status in chronically ill children attending special schools. METHODS: Overall, 642 children, median age 9.8 years (IQR 7.7-11.5), 60 % male, 72 % Caucasian, were included in this prospective study in nine special schools for chronically ill children in the Netherlands. Overall malnutrition was assessed as: acute malnutrition (<-2 SDS for weight for height (WFH)) and chronic malnutrition (<-2 SDS for height for age). The malnutrition risk was assessed with the nutritional risk-screening tool STRONGkids. Subjective health status was assessed with EQ-5D. RESULTS: Overall, 16 % of the children had overall malnutrition: 3 % acute and 13 % chronic malnutrition. Nurses reported 'some/severe problems' on the health status dimensions mobility (15 %), self-care (17 %), usual activities (19 %), pain/discomfort (22 %), and anxiety/depression (22 %) in chronically ill children. Their mean visual analogue scale score (VAS) was 73.0 (SD 11.1). Malnutrition, medication usage, and younger age explained 38 % of the variance of the VAS score. CONCLUSIONS: The presence of overall malnutrition in chronically ill children attending special schools was associated with lower subjective health status, especially in younger children and in those with chronic medication usage. Therefore, it is important to develop and use profile-screening tools to identify these children. PMID- 26362419 TI - Prospective validation study of Cernea classification for predicting EMG alterations of the external branch of the superior laryngeal nerve. AB - PURPOSES: Cernea classification is applied to describe the external branch of the superior laryngeal nerve (EBSLN). Using intraoperative neural monitoring we evaluated whether or not this classification is useful for predicting which EBSLN subtype has an increased risk of injury. METHODS: An analysis of 400 EBSLN. The identification of EBSLN was achieved with both cricothyroid muscle twitch and the glottis evoked electromyography response. We defined S1 initial EBSLN stimulation at identification and S2 final nerve stimulation achieved in the most cranial aspect of the nerve exposed above the area of surgical dissection after superior artery ligation. RESULTS: The mean S1 amplitude acquired was 259+/67 (180-421), 321 +/79 (192-391), 371 +/38 (200-551) MUV, respectively, for type 1, 2A, 2B (p = 0.08). The S1 and S2 amplitudes were similar in type 1 (p = 0.3). The S1 and S2 determinations changed significantly in type 2A and 2B (p = 0.04 and 0.03). EBSLN which demonstrated a >25 % decreased amplitude in S2 increased significantly from Type 1 (4.9 %) to Type 2A (11.2 %) and 2B (18 %) (p = 0.01). None of type 1, 2.8 % type 2A and 3 % type 2B showed a loss of EBSLN conductivity. The latency determinations did not vary significantly for any parameter compared. CONCLUSIONS: The Cernea classification was, therefore, found to predict the risk of EBSLN stress. We identified amplitude differences between S1 and S2 determinations in type 2A and 2B, thus confirming that surgical dissection in these subtypes is, therefore, extremely difficult to perform. PMID- 26362420 TI - A community-driven hypertension treatment group in rural Honduras. AB - BACKGROUND: We formed a self-funded hypertension treatment group in a resource poor community in rural Honduras. After training community health workers and creating protocols for standardized treatment, we used group membership fees to maintain the group, purchase generic medications in bulk on the local market, and hire a physician to manage treatment. We then assessed whether participation in the group improved treatment, medication adherence, and hypertension control. DESIGN: This is a program evaluation using quasi-experimental design and no control group. Using data from the 86 members of the hypertension treatment group, we analyzed baseline and follow-up surveys of members, along with 30 months of clinical records of treatment, medication adherence, and blood pressure readings. RESULTS: Our initial hypertension needs assessment revealed that at baseline, community hypertensives relied on the local Ministry of Health clinic as their source of anti-hypertensive medications and reported that irregular supply interfered with medication adherence. At baseline, hypertension group members were mainly female, overweight or obese, physically active, non-smoking, and non-drinking. After 30 months of managing the treatment group, we found a significant increase in medication adherence, from 54.8 to 76.2% (p<0.01), and hypertension control (<140/90 mmHg), from 31.4 to 54.7% (p<0.01). We also found a mean monthly decrease of 0.39 mmHg in systolic blood pressure (p<0.01). At the end of the 30-month observation period, the local Ministry of Health system had increased provision of low-cost anti-hypertensive medications and adopted the hypertension treatment group's treatment protocols. CONCLUSIONS: Formation of a self-funded, community-based hypertension treatment group in a rural, resource poor community is feasible, and group participation may improve treatment, medication adherence, and hypertension control and can serve as a political driver for improving hypertension treatment services provided by the public system. PMID- 26362421 TI - The use of cell phones and radio communication systems to reduce delays in getting help for pregnant women in low- and middle-income countries: a scoping review. AB - BACKGROUND: Delays in getting medical help are important factors in the deaths of many pregnant women and unborn children in the low- and middle-income countries (LMIC). Studies have suggested that the use of cell phones and radio communication systems might reduce such delays. OBJECTIVES: We review the literature regarding the impact of cell phones and radio communication systems on delays in getting medical help by pregnant women in the LMIC. DESIGN: Cochrane Library, PubMed, Maternity and Infant care (Ovid), Web of Science (ISI), and Google Scholar were searched for studies relating to the use of cell phones for maternal and child health services, supplemented with hand searches. We included studies in LMIC and in English involving the simple use of cell phones (or radio communication) to either make calls or send text messages. RESULTS: Fifteen studies met the inclusion criteria. All the studies, while of various designs, demonstrated positive contributory effects of cell phones or radio communication systems in reducing delays experienced by pregnant women in getting medical help. CONCLUSIONS: While the results suggested that cell phones could contribute in reducing delays, more studies of a longer duration are needed to strengthen the finding. PMID- 26362422 TI - Total elbow joint replacement for fractures in the elderly--Functional and radiological outcomes. AB - AIM: The purpose of this paper was to review the literature on the treatment of intra-articular fractures of the distal humerus in the elderly in order to evaluate the place for total elbow replacement (TER) in the light of our experience over the past 15 years. METHODS: A review of the records of 11 consecutive patients over the age of 60 years who underwent primary TER for comminuted fractures of the distal humerus between 1997 and 2011 were reviewed and the surviving patients were interviewed. The Scopus database was used to perform a pragmatic review of the literature published between the mid-1990s and the present-day. RESULTS: At the time of the most recent follow-up 3.5 years following surgery (range: 2-6 years) 7 patients assessed with the Mayo elbow performance index were classified as excellent, 4 were classified as good. There were no complications requiring further procedures encountered. Five surviving patients remain satisfied with the function of their TER. The number of papers recommending TER for treatment of these fractures continues to increase with time. CONCLUSIONS: TER is now the treatment of choice for unreconstructable fractures of the distal humerus in the elderly. This option should therefore be available at the time of surgery for all distal humeral fractures in this patient population. A surgical approach other than olecranon osteotomy, which would preclude TER is therefore required. PMID- 26362423 TI - Evaluation of Congenital Valvular Heart Diseases by the Pediatrician: When to Follow, When to Refer for Intervention? AB - Isolated congenital valvular heart disease in children constitutes a small fraction of congenital heart diseases. Valve involvement is seen more along with other congenital diseases. The most commonly involved valve is the pulmonary valve followed by the aortic valve. Stenotic lesions of the pulmonary and aortic valves are more frequently encountered than mitral and tricuspid valvular lesions. The presentation depends on the severity of the lesion and the age of the patient. Symptoms range from asymptomatic status to florid symptoms of valve obstruction and/or leak. Detailed clinical assessment and various imaging techniques confirm the diagnosis and help in management planning. Transcatheter balloon dilatation for obstructive pulmonary valve has very good long-term outcomes. The results of balloon dilation of aortic valve are also good enough for it to be the treatment of choice. Significant lesions of the mitral and tricuspid valve, regurgitant lesions, sub and supra valvular obstructions require surgical correction. Most valvar lesions mandate regular follow up. Communication and coordination between the pediatric cardiologist and the pediatrician helps in the optimal management. PMID- 26362424 TI - Algorithm for early discharge after total thyroidectomy using PTH to predict hypocalcemia: prospective study. AB - PURPOSE: Hypocalcemia is the most common complication after total thyroidectomy. The aim of this study was to determine whether postoperative parathyroid hormone (PTH) levels predict hypocalcemia in order to design an algorithm for early discharge. METHODS: We present a prospective study including patients who underwent total thyroidectomy. Hypocalcemia was defined as serum ionized calcium < 1.09 mmol/L or clinical evidence of hypocalcemia. PTH measurement was performed preoperatively and at 1, 3, and 6 h postoperatively. The percent decline of preoperative values was calculated for each time point. RESULTS: One hundred and six patients were included. Thirty-six (33.9%) patients presented hypocalcemia. A 50% decline in PTH levels at 3 h postoperatively showed the highest sensitivity and specificity to predict hypocalcemia (91 and 73%, respectively). No patients with a decrease <35% developed hypocalcemia (100% sensitivity), and all patients with a decrease >80% had hypocalcemia (100% specificity). CONCLUSIONS: PTH determination at 3 h postoperatively is a reliable predictor of hypocalcemia. According to the proposed algorithm, patients with less than 80% drop in PTH levels can be safely discharged the day of the surgery. PMID- 26362425 TI - Enucleation and evisceration at a tertiary care hospital in a developing country. AB - BACKGROUND: To analyze the demographics, indications, and surgical outcomes of anophthalmic surgery (enucleation and evisceration) at Jordan University Hospital during a 5-year period. METHODS: We conducted a retrospective chart review of patients who had undergone evisceration or enucleation between August 2006 and June 2011. The data collected included age at time of surgery, sex, affected eye, surgical indication, implant size, and postoperative complications. RESULTS: Anophthalmic surgery was performed for 68 eyes of 67 patients during the study period (42 (62 %) eviscerations and 26 (38 %) enucleations). Forty-three patients (64 %) were men, and 40 (59 %) eyes were right eyes. Trauma was the leading cause for anophthalmic surgery in 40 % of cases followed by a blind painful eye secondary to glaucoma (19 %) in the enucleation group and endophthalmitis (28.6 %) in the evisceration group. The most common anophthalmic surgery complication was wound dehiscence in 11.5 % of patients in the enucleation and 9.5 % in the evisceration groups. The mean and median sizes of the implants for evisceration were 16.6 and 18.0 mm, respectively; for enucleation, both were 20 mm. CONCLUSIONS: Evisceration was the preferred anophthalmic surgery in our series unless contraindicated. Trauma was the most common predisposing factor for evisceration and enucleation in our tertiary care center followed by blind painful eyes and endophthalmitis. The most common complication was wound dehiscence in both groups. PMID- 26362426 TI - Methodology manual for European Association for Cardio-Thoracic Surgery (EACTS) clinical guidelines. AB - The goal of all clinical guidelines is to assist patients and practitioners in making healthcare decisions. However, clinical guidelines have been questioned about their quality, transparency and independence. Based on the revision of manuals by other scientific cardiothoracic organizations, this document provides instructions for the development of European Association for Cardio-Thoracic Surgery (EACTS) clinical guidelines and other types of evidence-based documents. Four key areas have been addressed: (i) selection of taskforce members and transparency of relations with the industry, (ii) methods for critical appraisal of medical evidence, (iii) rules for writing recommendations and (iv) review process. It is hoped that, by adopting this methodology, clinical guidelines produced by the EACTS will be well balanced, objective and, importantly, trusted by physicians and patients who benefit from their implementation. PMID- 26362427 TI - Mid-term haemodynamic is important after implantation of a tissue valve but long term durability is what makes the difference. PMID- 26362428 TI - The combined role of sinuses of Valsalva and flow pulsatility improves energy loss of the aortic valve. AB - OBJECTIVES: Normal aortic valve opening and closing movement is a complex mechanism mainly regulated by the blood flow characteristics and the cyclic modifications of the aortic root. Our previous in vitro observations demonstrated that the presence of the Valsalva sinuses, independently from root compliance, is important in reducing systolic pressure drop across the aortic valve. This in vitro study was designed to ascertain if this effect is dependent on the flow characteristics. METHODS: Stentless 21, 23 and 25 mm aortic prostheses were sutured inside Dacron graft with and without sinuses. Hydrodynamic performance of the root models was investigated in steady-state (continuous) and unsteady-state (pulsatile) flow regimes. Aortic transvalvular pressure drop and effective orifice area (EOA) were evaluated. RESULTS: The continuous flow analysis revealed that no marked differences in pressure drop characterized the two root configurations at flow regimes lower than 15 l/min, independently of valve size. Conversely, at higher flow regimes (up to 30 l/min) a relatively low pressure drop continued to characterize grafts with sinuses, whereas marked increments in pressure drop were measured in straight grafts, especially in the smaller size (77.05 +/- 4.58 vs 23.80 +/- 2.44 mmHg; 18.40 +/- 1.31 vs 7.66 +/- 0.37 mmHg and 29.54 +/- 0.17 vs 7.12 +/- 0.07 mmHg, for 21, 23 and 25 mm valve, respectively). Under pulsatile conditions, the presence of sinuses clearly confirmed lower pressure drops also more evident in the smaller valve sizes (53.89 +/- 1.06 vs 11.6 +/- 0.24 mmHg at 7 l/min for 21 mm valve). EOA values were always lower in the absence of sinuses. In continuous flow regimes, at 30 l/min EOA of 25 mm valve size was 3.67 +/- 0.02 cm(2) in the Valsalva model versus 1.79 +/- 0.01 cm(2) for the Straight model. In pulsatile tests, at 7 l/min a 25-valve size demonstrated an EOA of 5.47 +/- 0.60 in the Valsalva model versus 2.50 +/- 0.02 cm(2) in the Straight model. CONCLUSIONS: These findings (i) confirm the hypothesis that the sinuses of Valsalva play a key role in optimizing the aortic haemodynamics during systole, minimizing energy losses; (ii) suggest that the sinuses of Valsalva are needed because of the complex nature of blood flow during ejection. PMID- 26362429 TI - Regulated drainage reduces the incidence of recurrence after uniportal video assisted thoracoscopic bullectomy for primary spontaneous pneumothorax: a propensity case-matched comparison of regulated and unregulated drainage?. AB - OBJECTIVES: To compare the recurrence rate of primary spontaneous pneumothorax (PSP) after uniportal video assisted thoracic surgery (VATS) bullectomy and mechanical pleurodesis in patients managed with a regulating pressure drainage system compared and those managed with a traditional one. METHODS: Retrospective propensity score case-matched analysis of 174 consecutive patients submitted to uniportal VATS bullectomy and mechanical pleural abrasion (2007-13) in two centres. Definition of recurrence: Recurrent PSP requiring new treatment (i.e. aspiration, chest tube reinsertion, reoperation) within 12 months from the operation. All patients were managed with a single 24-Fr chest tube. Group 1 (106 patients): Tube connected to a traditional device (T) maintained on wall suction (-20 cmH2O) for 48 h. Group 2 (68 patients): Tube connected to a regulating pressure device (R) set at -20 cmH2O for 48 h. Chest tube removal criteria: No air leak (no bubbling or air flow <20 ml/min for at least 8 h) and pleural effusion <200 ml/day. Propensity score case-matching analysis was performed using the following variables: Age, gender, height, weight, side of operation, dystrophic score, length of stapled parenchyma. RESULTS: The two groups of 68 pairs were well matched for baseline and surgical characteristics. Patients of Group 2 (R) showed a significantly lower incidence of recurrence rate compared with matched counterparts (T) (3, 4.4 vs 10, 14%, P = 0.041). There were no differences in persistent air leak incidence, chest tube duration or hospital stay between the groups. Group 2 had a higher 48-h output of pleural effusion compared with Group 1 (P < 0.0001). CONCLUSIONS: By stabilizing the pleural pressure at the preset values, novel regulating pressure devices may enhance pleurodesis, leading to a reduced incidence of PSP recurrences after uniportal VATS bullectomy and pleural abrasion. PMID- 26362433 TI - Full seven day NHS service is unachievable in near future, conference hears. PMID- 26362430 TI - Capsid display of a conserved human papillomavirus L2 peptide in the adenovirus 5 hexon protein: a candidate prophylactic hpv vaccine approach. AB - BACKGROUND: Infection by any one of 15 high risk human papillomavirus (hrHPV) types causes most invasive cervical cancers. Their oncogenic genome is encapsidated by L1 (major) and L2 (minor) coat proteins. Current HPV prophylactic vaccines are composed of L1 virus-like particles (VLP) that elicit type restricted immunity. An N-terminal region of L2 protein identified by neutralizing monoclonal antibodies comprises a protective epitope conserved among HPV types, but it is weakly immunogenic compared to L1 VLP. The major antigenic capsid protein of adenovirus type 5 (Ad5) is hexon which contains 9 hypervariable regions (HVRs) that form the immunodominant neutralizing epitopes. Insertion of weakly antigenic foreign B cell epitopes into these HVRs has shown promise in eliciting robust neutralizing antibody responses. Thus here we sought to generate a broadly protective prophylactic HPV vaccine candidate by inserting a conserved protective L2 epitope into the Ad5 hexon protein for VLP-like display. METHODS: Four recombinant adenoviruses were generated without significant compromise of viral replication by introduction of HPV16 amino acids L2 12-41 into Ad5 hexon, either by insertion into, or substitution of, either hexon HVR1 or HVR5. RESULTS: Vaccination of mice three times with each of these L2-recombinant adenoviruses induced similarly robust adenovirus-specific serum antibody but weak titers against L2. These L2-specific responses were enhanced by vaccination in the presence of alum and monophoryl lipid A adjuvant. Sera obtained after the third immunization exhibited low neutralizing antibody titers against HPV16 and HPV73. L2-recombinant adenovirus vaccination without adjuvant provided partial protection of mice against HPV16 challenge to either the vagina or skin. In contrast, vaccination with each L2-recombinant adenovirus formulated in adjuvant provided robust protection against vaginal challenge with HPV16, but not against HPV56. CONCLUSION: We conclude that introduction of HPV16 L2 12-41 epitope into Ad5 hexon HVR1 or HVR5 is a feasible method of generating a protective HPV vaccine, but further optimization is required to strengthen the L2-specific response and broaden protection to the more diverse hrHPV. PMID- 26362432 TI - Preoperative vocal cord paralysis and its association with malignant thyroid disease and other pathological features. AB - BACKGROUND: Vocal cord paralysis (VCP) is found in both benign and malignant thyroid disease. This study was performed to determine if the presence of preoperative VCP predicts malignancy. METHODS: A retrospective analysis was performed on a cohort of 1923 consecutive patients undergoing thyroid surgery. The incidence of preoperative VCP was recorded. Patient and nodule characteristics were correlated with final pathology. RESULTS: 1.3% of our cohort was found to have preoperative VCP. Malignant pathology was discovered in 76% of patients with preoperative VCP. Among these patients, 72% had a left sided paralysis. 10.5% of patients with preoperative VCP had perineural invasion (PNI) on final pathology, compared to 1.1% of patients with normal VC function. CONCLUSION: Preoperative VCP appears to be a strong, though not an absolute, indicator of malignancy. Most VCP were on the left side. Assessing for preoperative VCP is crucial in all patients who need thyroid surgery, as even benign nodules can be accompanied by preoperative vocal cord paralysis. PMID- 26362431 TI - Identification and validation of potential prognostic lncRNA biomarkers for predicting survival in patients with multiple myeloma. AB - BACKGROUND: Dysregulated long non-coding RNAs (lncRNAs) have been found to have oncogenic and/or tumor suppressive roles in the development and progression of cancer, implying their potentials as novel independent biomarkers for cancer diagnosis and prognosis. However, the prognostic significance of expression profile-based lncRNA signature for outcome prediction in patients with multiple myeloma (MM) has not yet been investigated. METHODS: LncRNA expression profiles of a large cohort of patients with MM were obtained and analyzed by repurposing the publically available microarray data. An lncRNA-focus risk score model was developed from the training dataset, and then validated in the testing and another two independent external datasets. The time-dependent receiver operating characteristic (ROC) curve was used to evaluate the prognostic performance for survival prediction. The biological function of prognostic lncRNAs was predicted using bioinformatics analysis. RESULTS: Four lncRNAs were identified to be significantly associated with overall survival (OS) of patients with MM in the training dataset, and were combined to develop a four-lncRNA prognostic signature to stratify patients into high-risk and low-risk groups. Patients of training dataset in the high-risk group exhibited shorter OS than those in the low-risk group (HR = 2.718, 95 % CI = 1.937-3.815, p <0.001). The similar prognostic values of four-lncRNA signature were observed in the testing dataset, entire GSE24080 dataset and another two independent external datasets. Multivariate Cox regression and stratified analysis showed that the prognostic power of four lncRNA signature was independent of clinical features, including serum beta 2 microglobulin (Sbeta2M), serum albumin (ALB) and lactate dehydrogenase (LDH). ROC analysis also demonstrated the better performance for predicting 3-year OS. Functional enrichment analysis suggested that these four lncRNAs may be involved in known genetic and epigenetic events linked to MM. CONCLUSIONS: Our results demonstrated potential application of lncRNAs as novel independent biomarkers for diagnosis and prognosis in MM. These lncRNA biomarkers may contribute to the understanding of underlying molecular basis of MM. PMID- 26362434 TI - Scholarly research productivity is not related to higher three-year licensure pass rates for physical therapy academic programs. AB - BACKGROUND: In the domain of academia, the scholarship of research may include, but not limited to, peer-reviewed publications, presentations, or grant submissions. Programmatic research productivity is one of many measures of academic program reputation and ranking. Another measure or tool for quantifying learning success among physical therapists education programs in the USA is 100 % three year pass rates of graduates on the standardized National Physical Therapy Examination (NPTE). In this study, we endeavored to determine if there was an association between research productivity through artifacts and 100 % three year pass rates on the NPTE. METHODS: This observational study involved using pre approved database exploration representing all accredited programs in the USA who graduated physical therapists during 2009, 2010 and 2011. Descriptive variables captured included raw research productivity artifacts such as peer reviewed publications and books, number of professional presentations, number of scholarly submissions, total grant dollars, and numbers of grants submitted. Descriptive statistics and comparisons (using chi square and t-tests) among program characteristics and research artifacts were calculated. Univariate logistic regression analyses, with appropriate control variables were used to determine associations between research artifacts and 100 % pass rates. RESULTS: Number of scholarly artifacts submitted, faculty with grants, and grant proposals submitted were significantly higher in programs with 100 % three year pass rates. However, after controlling for program characteristics such as grade point average, diversity percentage of cohort, public/private institution, and number of faculty, there were no significant associations between scholarly artifacts and 100 % three year pass rates. CONCLUSIONS: Factors outside of research artifacts are likely better predictors for passing the NPTE. PMID- 26362435 TI - Storying, fiction and philosophy: turning our attention to the traumatised or damaged nurse. AB - The Francis Report, the result of a UK public inquiry into ongoing mistreatment of patients at a large teaching hospital, revealed deep-rooted flaws in care delivery and professional performance. It led to regulatory review, policy initiatives and public outcry. To this point, it has not led to any extended or focused discussion on the sustenance or well-being of nurses so that we might avoid it happening again. This paper emerges from the writing and publication of a novel called Stranger Than Kindness and a subsequent PhD. The novel explored the themes of damaged or hurt healthcare professionals and their attempts at restoration or in one case, redemption. The paper uses the novel as 'data' for an articulation of the emotional world of (some) nurses and imports three theoretical perspectives; McGilchrist's work on the divided brain, Damasio's work on emotion and Merleau-Ponty's phenomenology to support an emerging philosophical position of embodied cognition. PMID- 26362437 TI - Differential Interactive Effects of Cartilage Traumatization and Blood Exposure In Vitro and In Vivo. AB - BACKGROUND: Sport injuries of the knee often lead to posttraumatic arthritis. In addition to direct damage of the cartilage, trauma-associated intra-articular bleeding may cause hemarthrosis. Both blood exposure and trauma are known to induce cell death and inflammation and to enhance proteoglycan release in cartilage. HYPOTHESIS: Blood exposure increases chondrocyte death as well as inflammatory and degenerative processes in traumatized cartilage. STUDY DESIGN: Controlled laboratory study. METHODS: Human macroscopically intact osteoarthritic (OA) cartilage explants were impacted by a drop-tower system (0.59 J) and cultivated with or without 10% blood. Interactive effects were studied concerning cell survival, gene expression, and the release of mediators over 24 hours and 96 hours. To evaluate the effects of trauma and hemarthrosis in vivo, a newly established blunt cartilage trauma model in the rabbit was used. Treatment of the knee joints of mature New Zealand White rabbits consisted of the following groups: control (C), arthrotomy (A), arthrotomy with cartilage trauma (AT; 1.0 J), and arthrotomy with cartilage trauma and blood injection (ATH). After 1 and 12 weeks, inflammatory mediators in the synovial fluid and histological changes of the cartilage were determined, and immunohistological staining was performed. RESULTS: The in vitro studies revealed a significant additional or synergistic effect of blood exposure on trauma-induced chondrocyte death, interleukin (IL) 1beta and prostaglandin-E2 (PGE2) release, and matrix metalloproteinase (MMP)/pro MMP level. Singular arthrotomy in vivo induced a temporary inflammation. Histologically, cartilage trauma caused significant OA changes that were not aggravated by an additional hemarthrosis. Trauma led to a persistent deposition of terminal complement complex (TCC), being enhanced by hemarthrosis. However, trauma-induced formation of osteophytes and arthrotomy-induced elevation of tumor necrosis factor-alpha release were reduced by hemarthrosis. CONCLUSION: While blood exposure clearly aggravated trauma-induced OA processes in the in vitro model, a singular blood injection revealed heterogeneous effects in vivo, enhancing TCC deposition but reducing trauma-induced osteophyte formation while the histological score of traumatized cartilage was not further impaired. CLINICAL RELEVANCE: The results of this study indicate that a singular, limited bleeding event might not exacerbate early trauma-induced cartilage degeneration in joint injuries. An early removal of intra-articular blood may not prevent the final resulting cartilage damage. PMID- 26362436 TI - Ruptured Tendons in Anabolic-Androgenic Steroid Users: A Cross-Sectional Cohort Study. AB - BACKGROUND: Accumulating case reports have described tendon rupture in men who use anabolic-androgenic steroids (AAS). However, no controlled study has assessed the history of tendon rupture in a large cohort of AAS users and comparison nonusers. HYPOTHESIS: Men reporting long-term AAS abuse would report an elevated lifetime incidence of tendon rupture compared with non-AAS-using bodybuilders. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Medical histories were obtained from 142 experienced male bodybuilders aged 35 to 55 years recruited in the course of 2 studies. Of these men, 88 reported at least 2 years of cumulative lifetime AAS use, and 54 reported no history of AAS use. In men reporting a history of tendon rupture, the circumstances of the injury, prodromal symptoms, concomitant drug or alcohol use, and details of current and lifetime AAS use (if applicable) were recorded. Surgical records were obtained for most participants. RESULTS: Nineteen (22%) of the AAS users, but only 3 (6%) of the nonusers, reported at least 1 lifetime tendon rupture. The hazard ratio for a first ruptured tendon in AAS users versus nonusers was 9.0 (95% CI, 2.5-32.3; P < .001). Several men reported 2 or more independent lifetime tendon ruptures. Interestingly, upper-body tendon ruptures occurred exclusively in the AAS group (15 [17%] AAS users vs 0 nonusers; risk difference, 0.17 [95% CI, 0.09-0.25]; P < .001 [hazard ratio not estimable]), whereas there was no significant difference between users and nonusers in risk for lower-body ruptures (6 [7%] AAS users, 3 [6%] nonusers; hazard ratio, 3.1 [95% CI, 0.7-13.8]; P = .13). Of 31 individual tendon ruptures assessed, only 6 (19%) occurred while weightlifting, with the majority occurring during other sports activities. Eight (26%) ruptures followed prodromal symptoms of nonspecific pain in the region. Virtually all ruptures were treated surgically, with complete or near-complete ultimate restoration of function. CONCLUSION: AAS abusers, compared with otherwise similar bodybuilders, showed a markedly increased risk of tendon ruptures, particularly upper-body tendon rupture. PMID- 26362439 TI - Estimating the Upper Limit of Lifetime Probability Distribution, Based on Data of Japanese Centenarians. AB - In modern biology, theories of aging fall mainly into two groups: damage theories and programed theories. If programed theories are true, the probability that human beings live beyond a specific age will be zero. In contrast, if damage theories are true, such an age does not exist, and a longevity record will be eventually destroyed. In this article, for examining real state, a special type of binomial model based on the generalized Pareto distribution has been applied to data of Japanese centenarians. From the results, it is concluded that the upper limit of lifetime probability distribution in the Japanese population has been estimated 123 years. PMID- 26362438 TI - Molecular Characterization of the NLRC4 Expression in Relation to Interleukin-18 Levels. AB - BACKGROUND: Interleukin-18 (IL-18) is a pleiotropic cytokine centrally involved in the cytokine cascade with complex immunomodulatory functions in innate and acquired immunity. Circulating IL-18 concentrations are associated with type 2 diabetes mellitus, cardiovascular events, and diverse inflammatory and autoimmune disorders. METHODS AND RESULTS: To identify causal variants affecting circulating IL-18 concentrations, we applied various omics and molecular biology approaches. By genome-wide association study, we confirmed association of IL-18 levels with a single nucleotide polymorphism in the untranslated exon 2 of the inflammasome component NLRC4 (NLR family, caspase recruitment domain-containing 4) gene on chromosome 2 (rs385076; P=2.4 * 10(-45)). Subsequent molecular analyses by gene expression analysis and reporter gene assays indicated an effect of rs385076 on NLRC4 expression and differential isoform usage by modulating binding of the transcription factor PU.1. CONCLUSIONS: Our study provides evidence for the functional causality of single nucleotide polymorphism rs385076 within the NLRC4 gene in relation to IL-18 activation. PMID- 26362440 TI - Parkinsonism in Older Adults and Its Association With Adverse Health Outcomes and Neuropathology. AB - BACKGROUND: Mild parkinsonian signs have been documented in community-dwelling older adults without Parkinson's disease. We estimated the proportion of older adults with parkinsonism and examined its association with adverse health outcomes and indices of brain pathology. METHODS: Four parkinsonian signs were assessed with the motor portion of the Unified Parkinson's Disease Rating Scale in 2,962 older adults who agreed to annual evaluation and brain autopsy. We used Cox proportional hazards models to examine the association of parkinsonism (two or more signs) and possible parkinsonism (one sign) with adverse health outcomes and regression models in 1,160 decedents to examine the association of parkinsonism and neuropathology. RESULTS: At study entry about 25% (N = 776, 26.2%) had parkinsonism and 30% had possible parkinsonism (N = 885, 29.9%). Parkinsonism was strongly related to age. The frequency was 11.8% for people younger than 75 years, 29.1% for those aged 75-84 years, and 43.7% for those aged 85 years or older. Parkinsonism was associated with an increased hazard of death, of mild cognitive impairment, of Alzheimer's disease and disability. Individuals with possible parkinsonism also had an increased risk for adverse health outcomes compared to individuals without parkinsonism. Postmortem indices of macroscopic and microscopic infarcts, arteriolosclerosis, and atherosclerosis were associated with parkinsonism proximate to death. CONCLUSIONS: Parkinsonism is common in older adults and is associated with an increased risk of adverse health outcomes and postmortem indices of brain pathology. Its association with age suggests that it will increase in our aging population. PMID- 26362441 TI - Serum uric acid level as a risk factor for acute kidney injury in hospitalized patients: a retrospective database analysis using the integrated medical information system at Kochi Medical School hospital. AB - BACKGROUND AND OBJECTIVES: Recent studies have shown that both low and high levels of serum uric acid (SUA) before cardiovascular surgery are independent risk factors for postoperative acute kidney injury (AKI). However, these studies were limited by their small sample sizes. Here, we investigated the association between SUA levels and AKI by performing a retrospective database analysis of almost 30 years of data from 81,770 hospitalized patients. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENT: Hospitalized patients aged >=18 years were retrospectively enrolled. AKI was diagnosed according to the Kidney Disease: Improving Global Outcomes 2012 Clinical Practice Guideline (KDIGO) criteria. Multivariate logistic regression analyses were performed to investigate the independent association between SUA levels and the incidence of AKI. SUA levels were treated as categorical variables because the relationship between SUA and the incidence of AKI has been suggested to be J-shaped or U-shaped. In addition to stratified SUA levels, we considered kidney function and related comorbidities, medications, and procedures performed prior to AKI onset as possible confounding risk factors. RESULTS: The final study cohort included 59,219 adult patients. Adjusted odds ratios of AKI incidence were higher in both the high- and low-SUA strata. Odds ratios tended to become larger in the higher range of SUA levels in women than in men. Additionally, this study showed that AKI risk was elevated in patients with SUA levels <=7 mg/dL. An SUA level >7 mg/dL is considered the point of initiation of uric acid crystallization. CONCLUSIONS: SUA level could be an independent risk factor for AKI development in hospitalized patients. Additionally, our results might suggest that intervention to lower SUA levels is necessary, even in cases of moderate elevation that does not warrant hyperuricemia treatment. Results also showed that SUA levels that require attention are lower for women than for men. PMID- 26362442 TI - Assessment of kidney function in children by enzymatic determination of 2- or 24 h creatinine clearance: comparison with inulin clearance. AB - BACKGROUND: Although renal inulin clearance (Cin) is the gold standard for evaluation of kidney function, it cannot be measured easily. Therefore, creatinine clearance (Ccr) is often used clinically to evaluate kidney function. Enzymatically measured Ccr was recently found to be much higher than Cin because of the tubular secretion of creatinine (Cr). This study compared three measures of renal clearance, inulin, 2-h Ccr, and 24-h Ccr, in children. METHODS: Kidney function was evaluated in 76 children (51 males and 25 females) aged 1 month to 18 years with chronic kidney disease (CKD) by three renal clearance methods at almost the same time. RESULTS: Correlations between each pair of three renal clearance measurements were determined. Approximate glomerular filtration rate (GFR) was equal to 62 % of 2-h Ccr or 76 % of 24-h Ccr. CONCLUSION: Cr secretion by renal tubules was approximately 50 % of the GFR. In this study, we indicate that the measurements of 2-h Ccr or 24-h Ccr do not show true GFR but we could infer approximate GFR from the values. The use of 2- or 24-h Ccr might contribute to the treatment of pediatric CKD patients. PMID- 26362443 TI - Rhinosinusitis in morbidity registrations in Dutch General Practice: a retro spective case-control study. AB - BACKGROUND: There is only limited accurate data on the epidemiology of rhinosinusitis in primary care. This study was conducted to assess the incidence of acute and chronic rhinosinusitis by analysing data from two Dutch general practice registration projects. Several patient characteristics and diseases are related to the diagnosis rhinosinusitis. METHODS: The Continuous Morbidity Registration (CMR) and the Transitionproject (TP) are used to analyse the data on rhinosinusitis in primary practice. Both registries use codes to register diagnoses. RESULTS: In the CMR 3244 patients are registered with rhinosinusitis and in the TP 5424 CMR: The absolute incidence of (acute) rhinosinusitis is 5191 (18.8 per 1000 patient years). Regarding an odds ratio of 5.58, having nasal polyps is strongest related to rhinosinusitis compared to the other evaluated comorbidities. A separate code for chronic rhinosinusitis exists, but is not in use. TP: Acute and chronic rhinosinusitis are coded as one diagnosis. The incidence of rhinosinusitis is 5574 or 28.7 per 1000 patient years. Patients who visit their general practitioner with "symptoms/complaints of sinus", allergic rhinitis and "other diseases of the respiratory system" have the highest chances to be diagnosed with rhinosinusitis. Medication is prescribed in 90.6 % of the cases. CONCLUSIONS: Rhinosinusitis is a common diagnosis in primary practice. In the used registries no difference could be made between acute and chronic rhinosinusitis, but they give insight in comorbidity and interventions taken by the GP in case of rhinosinusitis. PMID- 26362444 TI - "Targeting the Heart" in Heart Failure: Myocardial Recovery in Heart Failure With Reduced Ejection Fraction. AB - Myocardial recovery in heart failure (HF) is possible, but its determinants are not fully defined. At least partial functional improvement is possible with current evidence-based therapies. However, once significant HF symptoms develop, patients have varied trajectories, including: 1) structural and functional recovery; 2) stabilization (remission); and 3) acceleration to end-stage HF/death. All 3 trajectories may be interrupted by sudden death. These trajectories may represent the interplay of heterogeneous causality, genetic predeterminants, and disease phenotypes. Enhanced phenotypic description with cardiac magnetic resonance imaging, molecular imaging, or circulating biomarkers of the heterogeneous HF population may provide insights regarding specific biological targets amenable to existing and novel therapeutic strategies. The identification of patients in "remission," before progression to the end stage of predominantly nonviable tissue (e.g., fibrosis), has implications for clinical practice and future trials because such patients may be more likely to experience myocardial recovery (cardiac reserve). The identification of dysfunctional but viable myocardium and its diverse pathophysiological causes may provide opportunities to investigate existing and novel therapeutics aimed at enhancing myocardial recovery. PMID- 26362445 TI - Validation of a Simple Score to Determine Risk of Early Rejection After Pediatric Heart Transplantation. AB - OBJECTIVES: This study aimed to develop a reliable and feasible score to assess the risk of rejection in pediatric heart transplantation recipients during the first post-transplant year. BACKGROUND: The first post-transplant year is the most likely time for rejection to occur in pediatric heart transplantation. Rejection during this period is associated with worse outcomes. METHODS: The United Network for Organ Sharing database was queried for pediatric patients (age <18 years) who underwent isolated orthotopic heart transplantation from January 1, 2000 to December 31, 2012. Transplantations were divided into a derivation cohort (n = 2,686) and a validation (n = 509) cohort. The validation cohort was randomly selected from 20% of transplantations from 2005 to 2012. Covariates found to be associated with rejection (p < 0.2) were included in the initial multivariable logistic regression model. The final model was derived by including only variables independently associated with rejection. A risk score was then developed using relative magnitudes of the covariates' odds ratio. The score was then tested in the validation cohort. RESULTS: A 9-point risk score using 3 variables (age, cardiac diagnosis, and panel reactive antibody) was developed. Mean score in the derivation and validation cohorts were 4.5 +/- 2.6 and 4.8 +/- 2.7, respectively. A higher score was associated with an increased rate of rejection (score = 0, 10.6% in the validation cohort vs. score = 9, 40%; p < 0.01). In weighted regression analysis, the model-predicted risk of rejection correlated closely with the actual rates of rejection in the validation cohort (R(2) = 0.86; p < 0.01). CONCLUSIONS: The rejection score is accurate in determining the risk of early rejection in pediatric heart transplantation recipients. The score has the potential to be used in clinical practice to aid in determining the immunosuppressant regimen and the frequency of rejection surveillance in the first post-transplant year. PMID- 26362446 TI - Taking First Steps Toward Modeling Risk of Rejection in Children. PMID- 26362448 TI - Guanylyl Cyclase-A Receptor Activation With Natriuretic Propeptides. PMID- 26362447 TI - Pro-Atrial Natriuretic Peptide: A Novel Guanylyl Cyclase-A Receptor Activator That Goes Beyond Atrial and B-Type Natriuretic Peptides. AB - OBJECTIVES: The aim of this study was to determine if the atrial natriuretic peptide (ANP) precursor proANP is biologically active compared with ANP and B type natriuretic peptide (BNP). BACKGROUND: ProANP is produced in the atria and processed to ANP and activates the guanylyl cyclase receptor-A (GC-A) and its second messenger, cyclic guanosine monophosphate (cGMP). ProANP is found in the human circulation, but its bioavailability is undefined. METHODS: The in vivo actions of proANP compared with ANP, BNP, and placebo were investigated in normal canines (667 pmol/kg, n = 5/group). cGMP activation in human embryonic kidney 293 cells expressing GC-A or guanylyl cyclase receptor-B was also determined. ProANP processing and degradation were observed in serum from normal subjects (n = 13) and patients with heart failure (n = 14) ex vivo. RESULTS: ProANP had greater diuretic and natriuretic properties, with more sustained renal tubular actions, compared with ANP and BNP in vivo in normal canines, including marked renal vasodilation not observed with ANP or BNP. ProANP also resulted in greater and more prolonged cardiac unloading than ANP but much less hypotensive effects than BNP. ProANP stimulated cGMP generation by GC-A as much as ANP. ProANP was processed to ANP in serum from normal control subjects and patients with heart failure ex vivo. CONCLUSIONS: ProANP represents a novel activator of GC-A with enhanced diuretic, natriuretic, and renal vasodilating properties, and it may represent a key circulating natriuretic peptide in cardiorenal and blood pressure homeostasis. These results support the concepts that proANP may be a potential innovative therapeutic beyond ANP or BNP for cardiorenal diseases, including heart failure. PMID- 26362449 TI - Photoplethysmographic Signal to Screen Sleep-Disordered Breathing in Hospitalized Heart Failure Patients: Feasibility of a Prospective Clinical Pathway. AB - OBJECTIVES: The purpose of this study was to evaluate the plethysmographic signal derived oxygen desaturation index (ODI) as an inpatient screening strategy to identify sleep-disordered breathing (SDB) in patients with congestive heart failure (CHF). BACKGROUND: SDB is highly prevalent among patients hospitalized with CHF but is widely underdiagnosed. We evaluated overnight photoplethysmography as a possible screening strategy for hospitalized patients with CHF. METHODS: Consecutively admitted heart failure patients with high clinical suspicion of SDB and ODI >=5 were offered outpatient polysomnography (PSG), which was completed within 4 weeks of discharge. PSG was considered positive if the apnea hypoxia index (AHI) was >=5. A Bland-Altman plot was used to assess agreement between ODI and AHI. Receiver-operator characteristics were determined for ODI >=5 and AHI >=5. RESULTS: A screening questionnaire identified 246 of 282 consecutive patients with positive symptoms for SDB. Of these patients, 105 patients were offered further evaluation and 86 had ODI >=5 (mean ODI 17 +/- 17). Among these 86 patients, 68 underwent outpatient PSG within 4 weeks of discharge. PSG showed that 64 (94%) had SDB, with a mean AHI of 28. Inpatient ODI correlated well with PSG-derived AHI. The area under the curve was 0.82 for AHI >=5. The Bland-Altman plot revealed no major bias. Matthew's correlation coefficient revealed that the optimal cut-off for ODI is 5. CONCLUSIONS: Screening hospitalized patients with heart failure using targeted inpatient ODI identifies a cohort of patients with a high prevalence of SDB. Our screening strategy provides a potentially cost-effective method for early detection and treatment of SDB. PMID- 26362450 TI - Screening for Sleep-Disordered Breathing in Patients Hospitalized for Heart Failure. PMID- 26362451 TI - What Is a Life Worth?: A Tribute to Dr. William Little, a Pioneer in the Understanding of Heart Failure With Preserved Ejection Fraction. PMID- 26362452 TI - An adaptive real-time beat detection method for continuous pressure signals. AB - A novel adaptive real-time beat detection method for pressure related signals is proposed by virtue of an enhanced mean shift (EMS) algorithm. This EMS method consists of three components: spectral estimates of the heart rate, enhanced mean shift algorithm and classification logic. The Welch power spectral density method is employed to estimate the heart rate. An enhanced mean shift algorithm is then applied to improve the morphologic features of the blood pressure signals and detect the maxima of the blood pressure signals effectively. Finally, according to estimated heart rate, the classification logic is established to detect the locations of misdetections and over detections within the accepted heart rate limits. The parameters of the algorithm are adaptively tuned for ensuring its robustness in various heart rate conditions. The performance of the EMS method is validated with expert annotations of two standard databases and a non-invasive dataset. The results from this method show that the sensitivity (Se) and positive predictivity (+P) are significantly improved (i.e., Se > 99.45 %, +P > 98.28 %, and p value 0.0474) by comparison with the existing scheme from the previously published literature. PMID- 26362453 TI - Information diffusion, Facebook clusters, and the simplicial model of social aggregation: a computational simulation of simplicial diffusers for community health interventions. AB - By integrating the simplicial model of social aggregation with existing research on opinion leadership and diffusion networks, this article introduces the constructs of simplicial diffusers (mathematically defined as nodes embedded in simplexes; a simplex is a socially bonded cluster) and simplicial diffusing sets (mathematically defined as minimal covers of a simplicial complex; a simplicial complex is a social aggregation in which socially bonded clusters are embedded) to propose a strategic approach for information diffusion of cancer screenings as a health intervention on Facebook for community cancer prevention and control. This approach is novel in its incorporation of interpersonally bonded clusters, culturally distinct subgroups, and different united social entities that coexist within a larger community into a computational simulation to select sets of simplicial diffusers with the highest degree of information diffusion for health intervention dissemination. The unique contributions of the article also include seven propositions and five algorithmic steps for computationally modeling the simplicial model with Facebook data. PMID- 26362454 TI - The environment quality of heavy metals in sediments from the central Bohai Sea. AB - The heavy metals (Cu, Co, Ni, Zn, Cr, Pb, Cd) in surface and core sediments from the central Bohai Sea were analyzed to evaluate the temporal/spatial distribution and pollution status. Cd exhibited gradual increase vertically, while others were stable or declined slightly in core sediments. In surface sediments, metals showed higher values in 'central mud area of the Bohai Sea' and the coastal area of the Bohai Bay. Cd and Pb also had high levels in the northeastern part of Bohai Sea. Both the contamination factors (CFs) and the geo-accumulation index (Igeo) indicated that Cu, Co, Ni, and Cr were not at pollution levels, while Pb, Zn, and Cd indicated moderate contamination. Compared with sediment quality guidelines (SQGs), Cu, Zn, Cr, Pb, and Cd were likely to produce occasional adverse biological effects, while Ni showed possible ecotoxicological risks. The combined levels of the metals have a 21% probability of being toxic. PMID- 26362455 TI - Sources, concentrations and risk factors of organochlorine pesticides in soil, water and sediment in the Yellow River estuary. AB - The environmental occurrence, sources and risk factors of organochlorine pesticides (HCHs and DDTs) and their isomers or metabolites were studied using comprehensive surveys (including soil, surface water, groundwater and sediment sampling) conducted in the Yellow River Delta (YRD). HCHs and DDTs were all detected in multi environmental media. Compared with reported organochlorine pesticide values in China and abroad and with related environmental quality standards, the concentrations of HCHs and DDTs were generally at low levels in the YRD. Composition of OCPs (DDT metabolites and HCH isomers) showed that DDTs in the multiple environments of the YRD not only came from residues of dicofol but also from atmospheric deposition, while HCH pollution results from the historical usage of a mixture of technical HCH and lindane. Furthermore, the sum of Excess Lifetime Cancer Risk (?ELCR) exposure to HCHs exceeded the generally acceptable risk level of 1.0E-06 recommended by the USEPA for carcinogenic chemicals. PMID- 26362456 TI - Evaluation of steelmaking slag as basal media for coastal primary producers. AB - The use of granular steelmaking slag as a substitute for natural sand in the construction of tidal flats was investigated. Using an intertidal flat simulator, we evaluated dephosphorization slag mixed with 8% by dry weight of dredged sediment (DPS+DS) as a basal medium for the growth of benthic macro- and microalgae in comparison with silica sand mixed with 8% dredged sediment (SS+DS). Species compositions of macro- and microalgae were distinctly different between DPS+DS and SS+DS. The mean dry weight of macroalgae on DPS+DS was three orders of magnitude higher than that on SS+DS. Sediment shear strength and pH were higher in DPS+DS than in SS+DS or in the sediment of natural tidal flats. These results suggest that DPS contributes to changing the sediment environment, thereby changing the algal composition compared to the composition on natural tidal flats. PMID- 26362457 TI - Exceptionally high Cd levels and other trace elements in eggshells of American oystercatcher (Haematopus palliatus) from the Bahia Blanca Estuary, Argentina. AB - Concentrations of six trace metals were determined in the eggshells of American oystercatchers (Haematopus palliatus) from the Bahia Blanca estuary, Argentina. All metals measured in selected samples presented concentrations above the detection limit. Means found for Cu, Pb, Cr, Zn and Ni were as follow: 2.02+/ 0.52, 7.23+/-2.33, 0.78+/-0.03, 2.22+/-1.13 and 6.05+/-0.89mg/kg dw. The mean concentrations of Cd found were surprisingly high: 13.28+/-3.38mg/kg dw. Previous studies made on prey items of the American oystercatchers showed low to medium concentrations of the six trace metals. This may indicate a possible transfer of the metals that are available in the environment through food chains. Our study indicates that American oystercatchers sequester heavy metals in their eggshells. Therefore the eggshells may be useful as biomonitors for trace metal contamination in the Bahia Blanca estuary. PMID- 26362458 TI - The assessment of the spatial and seasonal variability of chromophoric dissolved organic matter in the Southern Yellow Sea and the East China Sea. AB - Samples of chromophoric dissolved organic matter (CDOM) from the Southern Yellow Sea (SYS) and the East China Sea (ECS) were evaluated by fluorescent Excitation Emission Matrix (EEM) combined with Parallel Factorial Analysis (PARAFAC). Three terrestrial humic-like components (C1, C2 and C3) and one autochthonous protein like component (C4) were identified. As for seasonal variations, CDOM displayed the following order on the whole: summer>spring>autumn. The C1, C2 and C3 components were mainly dominated by terrestrial inputs and their spatial distributions and temporal variations also can be influenced by primary productivity of phytoplankton, microbial activities and photobleaching. C4 was produced by phytoplankton and microorganisms and consumed by marine bacteria, and besides its distribution was attributed to the influence of riverine inputs. Terrestrial inputs were the dominant sources of CDOM in the SYS and ECS. PMID- 26362459 TI - Phase I and pharmacological trial of lapatinib in combination with gemcitabine in patients with advanced breast cancer. AB - BACKGROUND: Lapatinib has proven efficacy as monotherapy and in combination with capecitabine in patients with metastatic breast cancer (MBC) overexpressing HER2 and/or EGFR. Gemcitabine also has anti-tumor activity in MBC and a favourable toxicity profile. In this phase I study lapatinib and gemcitabine were combined. METHODS: Female patients with advanced BC were given lapatinib once daily (QD) in 28-day cycles with gemcitabine administered on day 1, 8 and 15. Physical examinations, vital signs and blood sampling for hematology, clinical chemistry and pharmacokinetics (PK) and radiological assessments of disease were performed at regular intervals. RESULTS: In total, 33 patients were included. Six dose limiting toxicities were observed, mostly grade 3 increases in liver function tests. Most common toxicities were fatigue (73%), nausea (70%), diarrhea (58%), increases in ALAT and ASAT (55 and 52%, respectively) and rash (46%). The maximum tolerated dose was lapatinib 1250 mg QD with gemcitabine 1000 mg/m(2). Lapatinib and gemcitabine PK did not appear to be influenced by each other. Anti-tumor activity was observed with one patient (4%) showing complete response and six (23%) partial response. CONCLUSION: Despite a slightly increased toxicity profile compared to their respective monotherapies, lapatinib and gemcitabine can be safely combined while showing signs of anti-tumor activity. PMID- 26362460 TI - Achieving the composite endpoint of glycated haemoglobin <7.0%, no weight gain and no hypoglycaemia in the once-weekly dulaglutide AWARD programme. AB - AIM: To compare the effectiveness of dulaglutide 1.5 and 0.75 mg with active comparators and placebo with regard to a composite endpoint of glycated haemoglobin (HbA1c), weight and hypoglycaemia, using post hoc analyses. METHODS: A logistic regression analysis was performed on the intention-to-treat population, using data from the last observation carried forward, and the composite endpoint of HbA1c <7.0% (53 mmol/mol), no weight gain (<=0 kg) and no hypoglycaemia (glucose <3.0 mmol/l or severe hypoglycaemia) after 26 weeks for each trial in the AWARD programme separately. RESULTS: At 26 weeks, within each study, 37-58% of patients on dulaglutide 1.5 mg, 27-49% of patients on dulaglutide 0.75 mg, and 9-61% of patients on active comparators achieved the composite endpoint. Significantly more patients reached the composite endpoint with dulaglutide 1.5 mg than with metformin, sitagliptin, exenatide twice daily or insulin glargine: odds ratio (OR) 1.5 [95% confidence interval (CI) 1.0, 2.2; p < 0.05], OR 4.5 (95% CI 3.0, 6.6; p < 0.001), OR 2.6 (95% CI 1.8, 3.7; p < 0.001) and OR 7.4 (95% CI 4.4, 12.6; p < 0.001), respectively, with no difference between dulaglutide 1.5 mg and liraglutide 1.8 mg. In addition, significantly more patients reached the composite endpoint with dulaglutide 0.75 mg than with sitagliptin or insulin glargine: OR 3.3 (95% CI 2.2, 4.8; p < 0.001) and OR 4.5 (95% CI 2.7, 7.8; p < 0.001), respectively. CONCLUSIONS: Dulaglutide is an effective treatment option, resulting in a similar or greater proportion of patients reaching the HbA1c target of <7.0% (53 mmol/mol), without weight gain or hypoglycaemia compared with active comparators. PMID- 26362461 TI - Denitrification of overlying water by microbial electrochemical snorkel. AB - A novel microbial electrochemical snorkel (MES) bioreactor was constructed by inserting an iron rod into the sediment of a simulated natural water body for the first time. Its nitrate removal performance and mechanism were investigated. The DNA high-throughput sequencing analysis indicates that denitrifying bacteria were grown on the iron rod in the overlying solution. The XRD analysis on the oxides formed on the surface of the iron rod indicates that they are goethite and green rust. In the MES system, the green rust on the iron rod can concentrate nitrate and denitrifying bacteria, forming an anaerobic biocathode. The denitrifying bacteria can reduce the nitrate into nitrogen with the electrons moved from the sediment. The nitrate removal efficiency reached 98% in 16days. This novel MES system showed excellent in-situ nitrate removal performance by moving and concentrating the electrons in sediment and the nitrate in overlying solution in an anaerobic microenvironment. PMID- 26362462 TI - Conversion of dried Aspergillus candidus mycelia grown on waste whey to biodiesel by in situ acid transesterification. AB - This study reports optimization of the transesterification reaction step on dried biomass of an oleaginous fungus Aspergillus candidus grown on agro-dairy waste, whey. Acid catalyzed transesterification was performed and variables affecting esterification, viz., catalyst methanol and chloroform concentrations, temperature, time, and biomass were investigated. Statistical optimization of the transesterification reaction using Plackett-Burman Design showed biomass to be the predominant factor with a 12.5-fold increase in total FAME from 25.6 to 320mg. Studies indicate that the transesterification efficiency in terms of conversion is favored by employing lower biomass loadings. A. candidus exhibited FAME profiles containing desirable saturated (30.2%), monounsaturated (31.5%) and polyunsaturated methyl esters (38.3%). The predicted and experimentally determined biodiesel properties (density, kinematic viscosity, iodine value, cetane number, TAN, water content, total and free glycerol) were in accordance with international (ASTM D6751, EN 14214) and national (IS 15607) standards. PMID- 26362463 TI - Subcritical hydrothermal pretreatment of olive mill solid waste for biofuel production. AB - The hydrothermal pretreatment of olive mill solid waste amended with 0.6M organic acids was studied at temperatures between 100 and 170 degrees C. Acetic and formic acids which are endogenous intermediates of hemiacetyl splitting at subcritical conditions were tested. Formic acid, with smaller molecular size and lower pKa, was found to be more effective than acetic in the entire range of temperatures tested. Yield of enzymatic hydrolysis was significantly enhanced (>2 folds) at temperatures above 140 degrees C. Concentration of aldehyde byproducts in the medium increased with temperature and pressure and addition of organic acids, however, the highest concentration detected (ca 1g/L) did not surpass values reported as inhibitory of sugars fermentation to ethanol by either yeast or bacteria. Aldehyde production was more affected by temperature than by acid addition. Concluding, addition of formic acid to hydrothermal pretreatment at relatively mild temperatures (140-170 degrees C) and pressure (10-13 atm) improved saccharification yield while saving energy. PMID- 26362464 TI - Development of a biomass torrefaction process integrated with oxy-fuel combustion. AB - Torrefaction of forest residues was studied under conditions relevant to oxy-fuel combustion flue gases. The results showed that the torrefaction in CO2 had a lower solid mass yield (81.36%) than that (83.06%) in N2. Addition of steam into CO2 (CO2/H2O=1/0.7 mole/mole) resulted in a higher mass yield (83.30%) compared to 81.36% in CO2. The energy yield was consistently increased from 79.17% to 84.12% or 88.32% for the torrefaction in N2, CO2, or the CO2 and steam mixture, respectively. On the other hand, additions of O2 into the mixture of steam and CO2 led to reductions in both mass yield (from 83.30% to 82.57% or 76.44%) and energy yield (from 88.32% to 84.65% or 79.16%, for the torrefaction in steam and CO2 without O2, with 5% v/v, or 10% v/v of O2, respectively). PMID- 26362465 TI - Development of the Italian Version of the Pain Vigilance and Awareness Questionnaire in Subjects with Chronic Low Back Pain: Cross-cultural Adaptation, Confirmatory Factor Analysis, Reliability and Validity. AB - BACKGROUND: Growing attention is being given to cognitive-behavioural measures to improve interventions for spinal disorders. The Pain Vigilance and Awareness Questionnaire (PVAQ) has never been validated in Italian subjects with chronic low back pain (LBP). PURPOSE: The purpose of this study is translating, culturally adapting and validating the Italian version of PVAQ (PVAQ-I). METHODS: A cross-sectional evaluation of the psychometric properties of the PVAQ-I on patients with chronic LBP was conducted. The questionnaire was culturally adapted in accordance with international standards. The psychometric testing included confirmatory factor analysis, reliability by internal consistency (Cronbach's alpha) and test-retest reliability (intra-class correlation coefficient, ICC); construct validity by comparing the PVAQ-I with the Pain Catastrophising Scale (PCS), the Tampa Scale of Kinesiophobia (TSK), the Hospital Anxiety and Depression Score (HADS), the Chronic Pain Acceptance Questionnaire (CPAQ), a Numerical Rating Scale of pain intensity (NRS) and the Oswestry Disability Questionnaire (ODI); and sensitivity to change by calculating the smallest detectable change. RESULTS: The PVAQ-I was administered to 131 subjects with chronic LBP (77 females, mean age of 48 +/- 16 years, median symptoms duration of 12 months). Factor analysis confirmed a two-factor (passive awareness and active vigilance), 13-item solution, which led to an acceptable data-model fit. Internal consistency (alpha = 0.91) and test-retest reliability (ICC = 0.92) were good. As a priori hypothesized, construct validity showed moderate correlations between the PVAQ-I and PCS (r = 0.60), TSK (r = 0.44) and HADS-Anxiety (r = 0.53) and low correlations with HADS-Depression (r = 0.28), NRS (r = 0.28), ODI (r = 0.23) and CPAQ (r = -0.12). The smallest detectable change was 9. CONCLUSION: The PVAQ was successfully translated into Italian and proved to have satisfactory psychometric properties. Its use is recommended for clinical and research purposes. PMID- 26362466 TI - Associations of Organizational Justice with Tinnitus and the Mediating Role of Depressive Symptoms and Burnout-Findings from a Cross-Sectional Study. AB - BACKGROUND: Tinnitus refers to the perception of a sound while an external source is absent. Research has identified work-related stress and its potential mental health-related sequelaes, i.e., depression and burnout, as risk factors for tinnitus. Perceived unfairness at work (organizational injustice), which is considered a psychosocial occupational stressor, has been shown to predict depression and burnout but its potential associations with tinnitus remains unaddressed. PURPOSE: The aim was to determine the relationship of organizational injustice with tinnitus, and to examine depression and burnout as potential mediators. METHOD: Cross-sectional data from a sample of 1632 employees were used. Tinnitus was assessed by self-report (n = 207; 13.9 %). Organizational justice and its subcomponents (interactional and procedural justice), burnout, and depressive symptoms were measured by validated questionnaires. Associations were assessed by logistic regressions, and mediation was assessed by maximum likelihood logistic regression estimations. RESULTS: Overall organizational justice, interactional and procedural justice were inversely related to tinnitus (z-score for overall justice: OR = 0.754; 95 % CI = 0.649 to 0.876). These associations were independent of demographics, socioeconomic status, job characteristics (including potential noise exposure), and health behaviors. Mediation analyses suggested a potential mediation by burnout (95 % CI indirect effect -0.188 to -0.066) and depressive symptoms (95 % CI indirect effect -0.160 to -0.043). Parallel multiple mediation analysis revealed that mediation through burnout was significantly larger than through depressive symptoms. CONCLUSION: Organizational justice appeared inversely related to tinnitus and this association was explained by individual differences in burnout symptoms, suggesting mediation. Longitudinal studies may further help to strengthen the evidence base for prevention of tinnitus through promotion of organizational justice and prevention of burnout. PMID- 26362467 TI - Environmental Susceptibility of the Sperm Epigenome During Windows of Male Germ Cell Development. AB - Male germ cells require multiple epigenetic reprogramming events during their lifespan to achieve reproductive capacity. An emerging body of compelling data demonstrates that environmental exposures can be embodied within the developing male germ cell as epigenetic marks. In turn, these epigenetic marks can impart information at fertilization to affect the trajectory of offspring health and development. While it is recognized that in utero epigenetic reprogramming of male germ cells is a particularly susceptible window to environmental exposures, other such windows exist during germ cell development. The objective of this review is to discuss epigenetic reprogramming events during male germ cell development and to provide supporting evidence from animal and human studies that during specific periods of development, germ cells are susceptible to environmentally induced epigenetic errors. Moving forward, the nascent field of sperm epigenetics research is likely to advance our understanding of paternal environmental determinants of offspring health and development. PMID- 26362468 TI - Cell death mechanisms of plant-derived anticancer drugs: beyond apoptosis. AB - Despite remarkable progress in the discovery and development of novel cancer therapeutics, cancer remains the second leading cause of death in the world. For many years, compounds derived from plants have been at the forefront as an important source of anticancer therapies and have played a vital role in the prevention and treatment of cancer because of their availability, and relatively low toxicity when compared with chemotherapy. More than 3000 plant species have been reported to treat cancer and about thirty plant-derived compounds have been isolated so far and have been tested in cancer clinical trials. The mechanisms of action of plant-derived anticancer drugs are numerous and most of them induce apoptotic cell death that may be intrinsic or extrinsic, and caspase and/or p53 dependent or independent mechanisms. Alternative modes of cell death by plant derived anticancer drugs are emerging and include mainly autophagy, necrosis-like programmed cell death, mitotic catastrophe, and senescence leading to cell death. Considering that the non-apoptotic cell death mechanisms of plant-derived anticancer drugs are less reviewed than the apoptotic ones, this paper attempts to focus on such alternative cell death pathways for some representative anticancer plant natural compounds in clinical development. In particular, emphasis will be on some promising polyphenolics such as resveratrol, curcumin, and genistein; alkaloids namely berberine, noscapine, and colchicine; terpenoids such as parthenolide, triptolide, and betulinic acid; and the organosulfur compound sulforaphane. The understanding of non-apoptotic cell death mechanisms induced by these drugs would provide insights into the possibility of exploiting novel molecular pathways and targets of plant-derived compounds for future cancer therapeutics. PMID- 26362470 TI - Hemothorax Management After Endovascular Treatment For Thoracic Aortic Rupture. AB - OBJECTIVES: The aim was to describe and analyze the management of hemothorax (HTX) and the occurrence of respiratory complications after endovascular repair of thoracic aortic rupture (TEVAR). METHODS: This was a multicenter study with retrospective analysis. Between November 2000 and December 2012, all patients with confirmed HTX due to rupture of the descending thoracic aorta treated with TEVAR were included. Respiratory function (acid base status, Pao2, Paco2, lactate, and respiratory index) was monitored throughout hospitalization. Primary endpoints were survival and post-operative respiratory complications. RESULTS: Fifty-six patients were treated. The mean age was 62 +/- 21 years (range 18-92 years). Etiology included traumatic rupture (n = 23, 41%), atherosclerotic aneurysm (n = 20, 36%), Debakey type IIIa dissection (n = 8, 14%), and penetrating aortic ulcer (n = 5, 9%). The primary technical success of TEVAR was 100%. The in hospital mortality rate was 12.5% (n = 7). Hemothorax was drained in 21 (37.5%) cases. In hospital respiratory complications occurred in 23 (41%) patients who required a longer intensive care unit stay (days 2.3 +/- 0.7 vs. 1.9 +/- 0.8, p = .017), and hospitalization (26 +/- 17 vs. 19 +/- 17, p = .021). Those who developed post-operative respiratory complications had lower pre operative PO2 values (mmHg, 80 +/- 24 vs. 91 +/- 21, p = .012). Respiratory complications and in hospital mortality did not differ among aortic pathologies (p = .269 and p = 1.0, respectively), nor did in hospital mortality differ between patients with and without respiratory complications (13% vs. 12%; p = .990). CONCLUSIONS: Thoracic aortic rupture still has a high mortality rate. Respiratory complications have not been eliminated by endovascular repair. HTX evacuation may have had a positive influence on the survival in these patients. Although traumatic and degenerative ruptures are two significantly different scenarios, survival and respiratory outcomes were similar and were not affected by the underlying aortic disease. PMID- 26362471 TI - Role of AKT and ERK pathways in controlling sensitivity to ionizing radiation and adaptive response induced by low-dose radiation in human immune cells. AB - Despite many studies of the effect of ionizing radiation, biological mechanisms of action might differ greatly depend on dose, dose rate, and cell type. This study was performed to explore the effects of low- and high-dose radiation in human immune cell lines. We examined cell sensitivity after irradiation with 0.05, 0.1, or 2Gy in two normal cell lines and three tumor cell lines. Low-dose radiation of 0.05 and 0.1Gy had no effect on cell survival in any tested cell line, with the exception of IM-9 cells, whose viability was transiently increased. However, IM-9 and C1R-sB7 cells were very sensitive to high-dose radiation-induced cell death, whereas Jurkat and JM1 cells showed moderate sensitivity, and THP-1 cells were completely resistant. This radiosensitivity was correlated with basal AKT activation, which is induced by phosphorylation. In radiosensitive IM-9 cells, priming with chronic low-dose irradiation blocked cell death induced by high-dose radiation challenge via inhibition of caspase activation and PARP cleavage. AKT phosphorylation was not altered in IM-9 cells, but ERK phosphorylation was greatly elevated immediately after chronic low-dose irradiation. Taken together, our results suggest that the different responses of normal and tumor cells to low-dose and high-dose radiation depend on AKT activation, which is regulated by protein phosphatase 2 (PP2A). In radiosensitive normal cells lacking basal AKT activity, chronic low-dose radiation increases activation of the ERK pathway, which plays an important role in the adaptive response to radiation, providing a very important insight into understanding the effects of ionizing radiation on health. PMID- 26362472 TI - EMPoWARed: Edmonton pediatric warfarin self-management study. AB - BACKGROUND: Patient self-management (PSM) in adults is safer and more cost effective than conventional management. Warfarin is a narrow therapeutic index drug with individual patient response to changes and frequently a long-term therapy. Children and their families are proposed to be able to effectively manage their child's warfarin therapy. Increased health related quality of life is highly associated with effective therapy in patients with chronic conditions. OBJECTIVES: The aim of this study is to evaluate the safety and efficacy of PSM over time including HRQOL and variables that may influence PFU success at PSM. PATIENTS/METHODS: Children and their family units (PFUs) current performing patient self-testing/monitoring for >= 3 months were enrolled in this cohort study. PFUs participated in comprehensive education on warfarin testing and management followed by an apprenticeship. Socio-demographic, clinical, and laboratory data were collected to evaluate safety and efficacy and health related quality of life. Outcomes were compared between the first 6 months on PSM (phase 1) and the last 6 months data collected on PSM (phase 2). RESULTS: Forty-two patients performed PSM for a median of 2.7 years (range: 1.1-6.2 years). Time in therapeutic range was 90% and 92.9% (p=0.30) in phases 1 and 2 respectively. All measures were strongly associated with improved heath related quality of life. PFUs socio-demographic status did not influence success at PSM. All PFUs maintained warfarin knowledge and INR testing competency. Warfarin dosing decision errors median 0 (range: 0-5, p=0.73) and a median 0 (range 0-4, p=0.55) per patient in phases 1 and 2 respectively. There were no adverse hemorrhagic or thrombotic events. CONCLUSIONS: Empowering PFUs to self-manage warfarin results in increased knowledge and understanding of their health condition, improved commitment to their health care and adherence to medication regimens and is demonstrated to be sustainable over time. PMID- 26362473 TI - C3435T polymorphism of the ABCB1 gene is associated with poor clopidogrel responsiveness in a Mexican population undergoing percutaneous coronary intervention. AB - BACKGROUND: Clopidogrel is a pro-drug and its intestinal absorption is limited by the P-glycoprotein encoded by the ABCB1 gene. It is metabolized hepatically by cytochrome P450 enzymes encoded by CYP genes to produce an active metabolite that antagonizes the P2Y12 platelet receptor. Some patients exhibit poor clopidogrel responsiveness due to polymorphisms, resulting in thrombotic events. The aim of this study was to determine the relationship between poor clopidogrel responsiveness and the ABCB1, CYP and P2RY12 gene polymorphisms among patients undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS: Two hundred seventy-six patients who underwent PCI were included in this study. Clopidogrel responsiveness was determined via optical aggregometry in platelet rich plasma using 10 MUM ADP. Patients exhibiting a platelet aggregation response higher than 70% were classified as poor responders. The genetic polymorphisms were analyzed via real-time PCR. Poor responsiveness to clopidogrel was noted in 22.1% of the patients. The TT genotype of the C3435T polymorphism of the ABCB1 gene and omeprazole usage were each associated with poor clopidogrel responsiveness (Exp (beta) 2.73, p=0.009 and Exp (beta) 3.86, p=0.04, respectively). CONCLUSION: Poor clopidogrel responsiveness is associated with the TT genotype of the C3435T polymorphism of the ABCB1 gene. PMID- 26362474 TI - Thromboelastography Identifies Cyclic Haemostatic Variations in Healthy Women Using Oral Contraceptives. AB - Using thromboelastography (TEG) and standard laboratory haemostatic tests we examined the influence of the menstrual cycle and monophasic oral contraceptive (OC) use on haemostasis in healthy women. Tests were performed on citrated whole blood and plasma (respectively) collected from 33 healthy non-pregnant women (18 non-OC users and 15 OC users) during menses, the follicular phase and the luteal phase of non-OC users, and the placebo, early-medicated phase, and late-medicated phase of OC users. Results for various coagulation parameters determined by TEG and standard laboratory haemostatic tests were compared within and between groups. TEG detected significantly increased coagulability in OC users during the late-medicated phase when compared to the placebo and early-medicated phases, whereas standard laboratory haemostatic tests failed to reveal significant differences in haemostasis within the OC steroid medication cycle. Neither TEG nor standard laboratory haemostatic tests detected significant differences in haemostasis within the menstrual cycle in non-OC users. When compared to non-OC users, TEG revealed that OC users had significantly increased coagulability only during the late-medicated phase; whereas standard laboratory haemostatic tests detected significant differences between all individual phases of the steroid medication cycle of OC users and the combined phases of the menstrual cycle in non-OC users. In conclusion, TEG provides additional insight into haemostatic function not identifiable using standard laboratory haemostatic tests. PMID- 26362475 TI - Eleven Asian countries pledge tougher action on tobacco. PMID- 26362476 TI - Evaluation of factors predicting clinical pleural injury during percutaneous nephrolithotomy: a prospective study. AB - The purpose of this study is to prospectively identify factors that predict the chance of pleural injury (detected clinically or on postoperative X-ray chest) during percutaneous nephrolithotomy (PCNL). All patients with renal/upper ureteric stones, undergoing PCNL between January 2013 and June 2014, were evaluated for pleural injury. An erect chest X-ray on inspiration was done within 6 h of PCNL. The patients were divided into Groups A and B depending on whether they developed or did not develop pleural injury. Patient-, stone-, renal-, and procedure-related factors were compared between the two groups. 332 patients with mean age 36.76 +/- 15.01 years (range 4-80) and M:F of 172:160 fulfilled the inclusion criteria. Pleural complications occurred in 10 patients (3 %). Of 141 patients with supracostal punctures (59 had additional infracostal punctures), 4.2 % (n = 6) had pleural injury. Of 191 patients with only infracostal punctures, 4 developed pleural injuries (2 %). Patients in group A had significantly lower age (27.00 +/- 11.18 vs. 37.06 +/- 15.03, p = 0.03) and lower BMI (18.0 +/- 1.90 vs. 21.12 +/- 2.24 p = 0.002). Incidence of pleural injury was significantly higher (p = 0.001) on right side [4.0 % (7/172) vs. 1.8 %, 3/160)]. Incidence of pleural injury had no association with staghorn calculi, stone surface area (590.51 +/- 313.88 for Group A vs. 593.02 +/- 387.10 for Group B; p = 0.11), degree of hydronephrosis, and operative time (65.13 +/- 19.45 for Group A vs. 72.21 +/- 19.56 for Group B; p = 0.06). On multivariate analysis, only low BMI and mean age <27 years were associated with higher risk of pleural injury. Higher incidence of pleural injury was noted in patients with low BMI and younger age. PMID- 26362477 TI - Activation of endothelial IKCa channels underlies NO-dependent myoendothelial feedback. AB - Agonist-induced vasoconstriction triggers a negative feedback response whereby movement of charged ions through gap junctions and/or release of endothelium derived (NO) limit further reductions in diameter, a mechanism termed myoendothelial feedback. Recent studies indicate that electrical myoendothelial feedback can be accounted for by flux of inositol trisphosphate (IP3) through myoendothelial gap junctions resulting in localized increases in endothelial Ca(2+) to activate intermediate conductance calcium-activated potassium (IKCa) channels, the resultant hyperpolarization then conducting back to the smooth muscle to attenuate agonist-induced depolarization and tone. In the present study we tested the hypothesis that activation of IKCa channels underlies NO-mediated myoendothelial feedback. Functional experiments showed that block of IP3 receptors, IKCa channels, gap junctions and transient receptor potential canonical type-3 (TRPC3) channels caused endothelium-dependent potentiation of agonist-induced increase in tone which was not additive with that caused by inhibition of NO synthase supporting a role for these proteins in NO-mediated myoendothelial feedback. Localized densities of IKCa and TRPC3 channels occurred at the internal elastic lamina/endothelial-smooth muscle interface in rat basilar arteries, potential communication sites between the two cell layers. Smooth muscle depolarization to contractile agonists was accompanied by IKCa channel mediated endothelial hyperpolarization providing the first demonstration of IKCa channel-mediated hyperpolarization of the endothelium in response to contractile agonists. Inhibition of IKCa channels, gap junctions, TRPC3 channels or NO synthase potentiated smooth muscle depolarization to agonists in a non-additive manner. Together these data indicate that rather being distinct pathways for the modulation of smooth muscle tone, NO and endothelial IKCa channels are involved in an integrated mechanism for the regulation of agonist-induced vasoconstriction. PMID- 26362478 TI - Early detection of psychosis: helpful or stigmatizing experience? A qualitative study. AB - AIM: Despite the large scientific debate concerning potential stigmatizing effects of identifying an individual as being in an at-risk mental state (ARMS) for psychosis, studies investigating this topic from the subjective perspective of patients are rare. This study assesses whether ARMS individuals experience stigmatization and to what extent being informed about the ARMS is experienced as helpful or harmful. METHODS: Eleven ARMS individuals, currently participating in the follow-up assessments of the prospective Basel Fruherkennung von Psychosen (FePsy; English: Early Detection of Psychosis) study, were interviewed in detail using a semistructured qualitative interview developed for this purpose. Data were analysed using Interpretative Phenomenological Analysis. RESULTS: Most individuals experiencing first symptoms reported sensing that there was 'something wrong with them' and felt in need of help. They were relieved that a specific term was assigned to their symptoms. The support received from the early detection centre was generally experienced as helpful. Many patients reported stigmatization and discrimination that appeared to be the result of altered behaviour and social withdrawal due to the prepsychotic symptoms they experienced prior to contact with the early detection clinic. CONCLUSIONS: The results suggest that early detection services help individuals cope with symptoms and potential stigmatization rather than enhancing or causing the latter. More emphasis should be put on the subjective experiences of those concerned when debating the advantages and disadvantages of early detection with regard to stigma. There was no evidence for increased perceived stigma and discrimination as a result of receiving information about the ARMS. PMID- 26362479 TI - Lipid-PEG conjugates sterically stabilize and reduce the toxicity of phytantriol based lyotropic liquid crystalline nanoparticles. AB - Lyotropic liquid crystalline nanoparticle dispersions are of interest as delivery vectors for biomedicine. Aqueous dispersions of liposomes, cubosomes, and hexosomes are commonly stabilized by nonionic amphiphilic block copolymers to prevent flocculation and phase separation. Pluronic stabilizers such as F127 are commonly used; however, there is increasing interest in using chemically reactive stabilizers for enhanced functionalization and specificity in therapeutic delivery applications. This study has explored the ability of 1,2-distearoyl-sn glycero-3-phosphoethanolamine conjugated with poly(ethylene glycol) (DSPE-PEGMW) (2000 Da <= MW <= 5000 Da) to engineer and stabilize phytantriol-based lyotropic liquid crystalline dispersions. The poly(ethylene glycol) (PEG) moiety provides a tunable handle to the headgroup hydrophilicity/hydrophobicity to allow access to a range of nanoarchitectures in these systems. Specifically, it was observed that increasing PEG molecular weight promotes greater interfacial curvature of the dispersions, with liposomes (Lalpha) present at lower PEG molecular weight (MW 2000 Da), and a propensity for cubosomes (QII(P) or QII(D) phase) at MW 3400 Da or 5000 Da. In comparison to Pluronic F127-stabilized cubosomes, those made using DSPE-PEG3400 or DSPE-PEG5000 had enlarged internal water channels. The toxicity of these cubosomes was assessed in vitro using A549 and CHO cell lines, with cubosomes prepared using DSPE-PEG5000 having reduced cytotoxicity relative to their Pluronic F127-stabilized analogues. PMID- 26362480 TI - Role of tympanometric volume in paediatric tympanoplasty. AB - OBJECTIVE: To determine the prognostic significance of "Tympaometric Volume" for paediatric tympanoplasty type I in a select age-group of 5-8 years. METHODS: A prospective study was conducted in 30 children with chronic suppurative otitis media-inactive mucosal disease of either sex. Pre-operative tympanometric volume was recorded in all the cases and statistically analysed with the graft uptake results post-operatively. All the patients underwent tympanoplasty type I by underlay technique using temporalis fascia graft. An intact graft at the end of 6 months, and a postoperative hearing improvement of 10 dB or greater in two consecutive frequencies, was regarded as surgical and audiological success, respectively. The statistical analysis was done using Mantel Haenszel chi(2) i.e. Chi square test, and Fisher exact p value test for confirmation. RESULTS: We recorded an impressive surgical success rate of 87% and an audiological improvement of 70% in this study. On the basis of mean tympanometric volume of 1.6 cm(3) the patients were divided into two groups: in Group A (tympanometric volume<1.6 cm(3)), and group B (tympanometric volume>1.6 cm(3)). A graft uptake of 95% and 77% was recorded in Group A & B, respectively. However, the statistical evaluation of the data revealed no significant effect of this factor. CONCLUSIONS: In this study no correlation between the tympanometric volume and the surgical success of paediatric tympanoplasty in select age group of 5-8 years was observed. PMID- 26362481 TI - Paediatric subglottic stenosis - Have things changed? Our experience from a developing tertiary referral centre. AB - BACKGROUND: Paediatric airway disorders are common, particularly in the context of improved ventilation methods for neonates in intensive care units. Management is not standardised. OBJECTIVES: To assess the number, severity, management and outcomes of all patients diagnosed with subglottic stenosis at a developing tertiary referral centre. STUDY DESIGN: 19 month prospective longitudinal study. STUDY POPULATION: All patients who underwent microlaryngobronchoscopy (MLB) were included. Subglottic stenosis (SGS) was graded intraoperatively using the Myer Cotton classification. RESULTS: 102 patients underwent MLB during this period. 33 of 102 patients (32.4%) were diagnosed with SGS+/-other co-pathologies. Mean and median age at diagnostic procedure were 24.7 months (SD 23.5) and 18 months, respectively. At their first MLB, 22 of 33 patients (66.7%) were found to have a Grade 1 SGS, 7 of 33 (21.2%) were Grade 2 and the remaining 4 of 33 (12.1%) were Grade 3. We had no patients with Grade 4 SGS. During this period, these patients with SGS underwent 73 MLBs+/-interventions (2.21 per patient) such as incision and balloon dilatation, tracheostomy (2 of 33) or ultimately, laryngotracheal reconstruction (LTR) (2 of 33). A further 3 patients have since undergone LTR. No significant unexpected events occurred. CONCLUSIONS: These findings suggest that subglottic stenosis may be evolving in terms of its presentation and management. Management can more often be endoscopic and perhaps avoid tracheostomy or laryngotracheal reconstruction. Further long term prospective studies are required. PMID- 26362482 TI - The utility of bronchoalveolar lavage findings in the diagnosis of eosinophilic esophagitis in children. AB - INTRODUCTION: Bronchoalveolar lavage (BAL)-nucleated cell counts and the lipid laden alveolar macrophage index (LLMI) have been investigated in predicting chronic aspiration as well as reflux esophagitis with variable results. To date, BAL neutrophil percentages and the LLMI have not been described in patients with eosinophilic esophagitis (EoE). OBJECTIVES: To evaluate BAL neutrophil percentages and LLMI levels in patients with EoE and compare these levels in patients with aerodigestive concerns without biopsy-proven EoE. METHODS: Retrospective review of patients referred to an aerodigestive evaluation team for overlapping aerodigestive complaints (dysphagia, stridor, subglottic stenosis, feeding intolerance, and chronic aspiration). Patients underwent microlaryngoscopy, esophagogastroduodenoscopy with biopsy, and bronchoscopy and BAL were indicated by symptoms. BAL neutrophil percentages, LLMI levels, esophageal biopsy results, and esophageal dual-probe pH/impedance were recorded and compared. RESULTS: Fifty-one patients were included in the study that underwent comprehensive workup for aerodigestive complaints. Patients were subdivided into two groups: (1) negative esophageal biopsy (for EoE) and (2) positive esophageal biopsy. There were no significant differences between the groups in percentage neutrophils (p=0.55, unpaired t-test) or LLMI levels (p=0.14, unpaired t-test). DISCUSSION: BAL neutrophil percentages and the LLMI are unreliable in identifying patients with silent aspiration and gastroesophageal reflux. To date, there is no report of the utility of BAL neutrophil percentages and the LLMI in diagnosing patients with EoE. Our series indicates no correlation in neutrophil percentages or LLMI in patients with EoE versus patients without EoE that are referred to tertiary centers with aerodigestive concerns. CONCLUSION: BAL neutrophil percentages and LLMI levels are not a reliable predictor of eosinophilic esophagitis in children with complex aerodigestive concerns. Esophageal biopsy remains the gold standard for diagnosis of EoE and the challenge remains to find other markers that raise suspicion for EoE for the non-gastroenterologist or that stage the extent of disease beyond the esophagus. PMID- 26362484 TI - Assessment of testicular dose during preoperative radiotherapy for rectal cancer. AB - BACKGROUND: Radiotherapy (RT) for rectal cancer can have adverse effects on testicular function resulting in azoospermia and low testosterone levels. Variability of testicular dose (TD) due to differences in position of testes has been assessed with scrotal dosimeters and resulted in substantial variability of delivered TD. The aim of this study was to estimate planned and delivered TD using a treatment planning system (TPS). METHODS: In 101 men treated with RT for rectal cancer the cumulative mean TD (mTD) was calculated by TPS based on plan computed tomography (CT) to evaluate the effect of different predictors on planned TD. The delivered TD was estimated by TPS based on repeated cone-beam CTs in 32 of 101 men to assess within-person variability of planned and delivered TD in a longitudinal analysis. RESULTS: The median planned mTD for short course RT was 0.57 Gy (range 0.06-14.37 Gy) and 0.81 Gy (range 0.36-10.80 Gy) for long course RT. The median planned mTD was similar to the median delivered mTD in the 32 men analysed over the entire course of RT (p=0.84). The mTD did not change significantly over time of planning and delivering RT. The variation in proximity between testes and planning target volume (PTV) was related to within-person variability of mTD in men on the 50th and 75th percentile of mTD and as expected the absolute difference between planned and delivered mTD increased with higher mTD. CONCLUSION: Testicular doses calculated based on plan-CT are an accurate estimation of delivered TD based on repeated cone beam (CB)CT. The within-person variability of TD is related to variation in proximity between testes and PTV in men with moderate to high TD. PMID- 26362483 TI - Changes in the amino acid sequence of the recombinant human factor VIIa analog, vatreptacog alfa, are associated with clinical immunogenicity. AB - BACKGROUND: Vatreptacog alfa, a recombinant human factor VIIa (rFVIIa) analog developed to improve the treatment of bleeds in hemophilia patients with inhibitors, differs from native FVIIa by three amino acid substitutions. In a randomized, double-blind, crossover, confirmatory phase III trial (adept(TM) 2), 8/72 (11%) hemophilia A or B patients with inhibitors treated for acute bleeds developed anti-drug antibodies (ADAs) to vatreptacog alfa. OBJECTIVES: To characterize the formation of anti-vatreptacog alfa ADAs in hemophilia patients with inhibitors. METHODS/PATIENTS: This was a post hoc analysis of adept(TM) 2. Immunoglobulin isotype determination, specificity analysis of rFVIIa cross reactive antibodies, epitope mapping of rFVIIa single mutant analogs and pharmacokinetic (PK) profiling were performed to characterize the ADAs. RESULTS: Immunoglobulin isotyping indicated that the ADAs were of the immunoglobulin G subtype. In epitope mapping, none of the rFVIIa single mutant analogs (V158D, E296V or M298Q) contained the complete antibody epitope, confirming that the antibodies were specific for vatreptacog alfa. In two patients, for whom PK profiling was performed both before and after the development of ADAs, vatreptacog alfa showed a prolonged elimination phase following ADA development. During the follow-up evaluation, the rFVIIa cross-reactivity disappeared after the last vatreptacog alfa exposure, despite continued exposure to rFVIIa as part of standard care. CONCLUSIONS: Results from the vatreptacog alfa phase III trial demonstrate that the specific changes made, albeit relatively small, to the FVIIa molecule alter its clinical immunogenicity. PMID- 26362485 TI - Targeted temperature management and neuroprognostication after cardiac arrest: A survey in Belgium. PMID- 26362469 TI - The Physiology, Pathology, and Pharmacology of Voltage-Gated Calcium Channels and Their Future Therapeutic Potential. AB - Voltage-gated calcium channels are required for many key functions in the body. In this review, the different subtypes of voltage-gated calcium channels are described and their physiologic roles and pharmacology are outlined. We describe the current uses of drugs interacting with the different calcium channel subtypes and subunits, as well as specific areas in which there is strong potential for future drug development. Current therapeutic agents include drugs targeting L type Ca(V)1.2 calcium channels, particularly 1,4-dihydropyridines, which are widely used in the treatment of hypertension. T-type (Ca(V)3) channels are a target of ethosuximide, widely used in absence epilepsy. The auxiliary subunit alpha2delta-1 is the therapeutic target of the gabapentinoid drugs, which are of value in certain epilepsies and chronic neuropathic pain. The limited use of intrathecal ziconotide, a peptide blocker of N-type (Ca(V)2.2) calcium channels, as a treatment of intractable pain, gives an indication that these channels represent excellent drug targets for various pain conditions. We describe how selectivity for different subtypes of calcium channels (e.g., Ca(V)1.2 and Ca(V)1.3 L-type channels) may be achieved in the future by exploiting differences between channel isoforms in terms of sequence and biophysical properties, variation in splicing in different target tissues, and differences in the properties of the target tissues themselves in terms of membrane potential or firing frequency. Thus, use-dependent blockers of the different isoforms could selectively block calcium channels in particular pathologies, such as nociceptive neurons in pain states or in epileptic brain circuits. Of important future potential are selective Ca(V)1.3 blockers for neuropsychiatric diseases, neuroprotection in Parkinson's disease, and resistant hypertension. In addition, selective or nonselective T-type channel blockers are considered potential therapeutic targets in epilepsy, pain, obesity, sleep, and anxiety. Use-dependent N-type calcium channel blockers are likely to be of therapeutic use in chronic pain conditions. Thus, more selective calcium channel blockers hold promise for therapeutic intervention. PMID- 26362486 TI - The prevalence and significance of abnormal vital signs prior to in-hospital cardiac arrest. AB - BACKGROUND: Patients suffering in-hospital cardiac arrest often show signs of physiological deterioration before the event. The purpose of this study was to determine the prevalence of abnormal vital signs 1-4h before cardiac arrest, and to evaluate the association between these vital sign abnormalities and in hospital mortality. METHODS: We included adults from the Get With the Guidelines((r))- Resuscitation registry with an in-hospital cardiac arrest. We used two a priori definitions for vital signs: abnormal (heart rate (HR) <= 60 or >= 100 min(-1), respiratory rate (RR) <= 10 or >20 min(-1) and systolic blood pressure (SBP) <= 90 mm Hg) and severely abnormal (HR <= 50 or >= 130 min(-1), RR <= 8 or >= 30 min(-1) and SBP <= 80 mm Hg). We evaluated the association between the number of abnormal vital signs and in-hospital mortality using a multivariable logistic regression model. RESULTS: 7851 patients were included. Individual vital signs were associated with in-hospital mortality. The majority of patients (59.4%) had at least one abnormal vital sign 1-4h before the arrest and 13.4% had at least one severely abnormal sign. We found a step-wise increase in mortality with increasing number of abnormal vital signs within the abnormal (odds ratio (OR) 1.53 (CI: 1.42-1.64) and severely abnormal groups (OR 1.62 (CI: 1.38-1.90)). This remained in multivariable analysis (abnormal: OR 1.38 (CI: 1.28 1.48), and severely abnormal: OR 1.40 (CI: 1.18-1.65)). CONCLUSION: Abnormal vital signs are prevalent 1-4h before in-hospital cardiac arrest on hospital wards. In-hospital mortality increases with increasing number of pre-arrest abnormal vital signs as well as increased severity of vital sign derangements. PMID- 26362487 TI - The effect of targeted temperature management on coagulation parameters and bleeding events after out-of-hospital cardiac arrest of presumed cardiac cause. AB - AIMS: Targeted temperature management (TTM) is part of the standard treatment of comatose patients after out-of-hospital cardiac arrest (OHCA) to attenuate neurological injury. In other clinical settings, hypothermia promotes coagulopathy leading to an increase in bleeding and thrombosis tendency. Thus, concern has been raised as to whether TTM can be applied safely, as acute myocardial infarction requiring primary percutaneous coronary intervention (PCI) with the need of effective antiplatelet therapy is frequent following OHCA. This study investigated the influence of TTM at 33 or 36 degrees C on various laboratory and coagulation parameters. METHODS AND RESULTS: In this single-center predefined substudy of the TTM trial, 171 patients were randomized to TTM at either 33 or 36 degrees C in the postresuscitation phase. The two subgroups were compared regarding standard laboratory coagulation parameters, thrombelastography (TEG), bleeding, and stent thrombosis events. Platelet counts were lower in the TTM33-group compared to TTM36 (p=0.009), but neither standard coagulation nor TEG parameters showed any difference between the groups. TEG revealed a normocoagulable state in the majority of patients, while approximately 20% of the population presented as hypercoagulable. Adverse events included 38 bleeding events, one stent thrombosis, and one reinfarction, with no significant difference between the groups. CONCLUSIONS: There was no evidence supporting the assumption that TTM at 33 degrees C was associated with impaired hemostasis or increased the frequency of adverse bleeding and thrombotic events compared to TTM at 36 degrees C. We found that TTM at either temperature can safely be applied in the postresuscitation phase after acute myocardial infarction and primary PCI. PMID- 26362488 TI - Compensating for poor primary implant stability in different bone densities by varying implant geometry: a laboratory study. AB - The aim of this study was to determine the influence of implant diameter and length on primary stability in artificial bone blocks. In total, 240 implants of various diameters (O 3.3, 4.1, and 4.8mm) and lengths (8 and 12 mm) were inserted in four artificial bone blocks of different densities (D1-D4). The primary stability for each bone block density was measured and compared with the primary stability of a narrow and short implant (O 3.3mm, length 8mm) in the next higher density block. Analysis was done by three-way ANOVA, and mean differences were determined with the 95% confidence interval. Levels of primary stability achieved by choosing the next higher diameter or length were not comparable to those of the next level of block density. However, equivalent values could be achieved by selecting the largest diameter for short and long implants in the lowest block density D4, as well as for long implants in bone type D2. The diameter of an implant has greater influence on primary stability than length. In particular, in the case of poor bone quality, a variation of implant geometry can lead to significant improvement in primary stability. PMID- 26362489 TI - Systematic review and meta-analysis of the efficacy of hilotherapy following oral and maxillofacial surgery. AB - Craniofacial surgery causes immediate postoperative pain, oedema, and functional limitations. Hilotherapy delivers cooled water to the face at 15 degrees C and may reduce the postoperative recovery time. This work presents a meta-analysis of short-term postoperative outcomes after hilotherapy. Following a systematic literature search, comparative trials of patients undergoing surgical interventions in the maxillofacial region and receiving either hilotherapy or ice cooling therapy were included for meta-analysis. Demographics and surgical outcomes were extracted. Data were analysed using Comprehensive Meta-Analysis software. Mean (SEM) data were calculated for demographic variables and standardized mean differences with the 95% confidence interval for surgical outcomes. Five trials were analysed, providing 206 patients for evaluation; mean patient age was 29.4 (9.4) years. Hilotherapy reduced pain (10-point visual analogue scale) at 48 h (P<0.010) and 72 h (P<0.050), as well as postoperative facial oedema (P<0.010), compared to ice-cooling treatment. Trismus and facial neurological scores were also improved (P=0.08). Patients preferred hilotherapy to other cooling methods (P<0.010). Hilotherapy appears to be effective in reducing postoperative facial pain, oedema, and trismus, and in improving patient reported outcomes. Well-designed randomized controlled clinical trials are required to clarify the procedure-specific efficacy of postoperative hilotherapy and optimal durations of treatment. PMID- 26362490 TI - Thyroid abscess: A case report. PMID- 26362491 TI - Endoscopic septoplasty: Tips and pearls. AB - This article is designed to provide a step-by-step description of our endoscopic septoplasty technique and discuss its difficulties and technical tips. Endoscopic septoplasty comprises 10 steps: diagnostic endoscopy, subperichondral infiltration, left mucosal incision, dissection of the left subperichondral flap, cartilage incision (0.5 centimetre posterior to the mucosal incision), dissection of the right subperichondral flap, anterior cartilage resection, perpendicular plate dissection, dissection and resection of the maxillary crest, endoscopic revision, mucosal suture and Silastic stents. A satisfactory postoperative result was observed at 3 months in 97% of cases in this series. The main contraindication to endoscopic septoplasty is anterior columellar deviation of the nasal septum requiring a conventional procedure. PMID- 26362492 TI - Apnoea and delayed cardiorespiratory arrest after endoscopy for oropharyngeal squamous cell carcinoma. PMID- 26362493 TI - A case of retrobulbar optic neuritis caused by duloxetine. AB - Psychotropic medications may cause many ocular adverse effects including toxic optic neuropathy. We present a unique case of a 44-year-old woman using duloxetine who presented with unilateral visual loss due to retrobulbar neuritis. Physicians and patients should be alerted to this potential side effect. To the best of our knowledge, this is the first case of developing retrobulbar neuritis related to duloxetine usage. PMID- 26362494 TI - Pre-stimulus alpha and post-stimulus N2 foreshadow imminent errors in a single task. AB - Performance errors have been attributed to distinct neural mechanisms in different tasks. Two temporally and physiologically dissociable neural patterns prior to errors, i.e., pre-stimulus alpha (8-13 Hz) power indicative of sustained attention and post-stimulus N2 amplitude indicative of cognitive control, have been widely (but independently) reported in many studies. However, it is still largely unknown whether these two neural mechanisms for error commission exist in a single task at the same time and, if so, whether they can be probed simultaneously and how they lead to response accuracy (collectively or separately). To this end, we measured high-density electroencephalography (EEG) signals in a color-word matching Stroop task. We quantified both patterns on EEG data from individual stimulus condition (congruent or incongruent), as well as on pooled data from both conditions. Enhanced pre-stimulus alpha power for errors was identified over the parieto-occipital area in the congruent condition and the pooled data. Reduced post-stimulus N2 amplitude was only revealed in the incongruent condition. More importantly, for the first time, a balanced interaction between these two EEG patterns was revealed in correct trials, but not in error trials. These findings suggest that errors in one task could occur due to distinct neural mechanisms, e.g., poor sustained attention, poor cognitive control, or missed balance between these two. The present results further suggest that the detection of neural patterns related to different neural mechanisms could be complicated by other modulation factors, such as stimulus condition. Therefore, more than one neural marker should be simultaneously monitored to effectively predict imminent errors. PMID- 26362495 TI - Present status, actions taken and future considerations due to the findings of E. multilocularis in two Scandinavian countries. AB - When Echinococcus (E.) multilocularis was first detected in mainland Scandinavia in Denmark in 2000, surveillance was initiated/intensified in Sweden, mainland Norway and Finland. After 10 years of surveillance these countries all fulfilled the requirements of freedom from E. multilocularis as defined by the EU, i.e. a prevalence in final hosts <1% with 95% confidence level. However, in 2011 E. multilocularis was detected in Sweden for the first time and surveillance was increased in all four countries. Finland and mainland Norway are currently considered free from E. multilocularis, whereas the prevalence in foxes in Sweden and Denmark is approximately 0.1% and 1.0%, respectively. E. multilocularis has been found in foxes from three different areas in Denmark: Copenhagen (2000), Hojer (2012-14) and Grindsted (2014). Unlike Sweden, Norway and Finland, human alveolar echinococcosis (AE) is not notifiable in Denmark, and the number of human cases is therefore unknown. In Sweden, E. multilocularis has been found in foxes in four counties, Vastra Gotaland, Sodermanland, Dalarna (2011) and Smaland (2014). E. multilocularis has also been found in an intermediate host in Sodermanland (2014). Two cases of AE have been reported in humans (2012), both infected abroad. No cases of E. multilocularis or AE have been reported in Finland and Norway. Recommendations and future considerations are discussed further. PMID- 26362497 TI - Consideration of all evidence about community treatment orders. PMID- 26362496 TI - Effect of increased compulsion on readmission to hospital or disengagement from community services for patients with psychosis: follow-up of a cohort from the OCTET trial. AB - BACKGROUND: Community treatment orders (CTOs) have not been shown in randomised trials to reduce readmission to hospital in patients with psychosis, but these trials have been short (11-12 months). We previously investigated the effect of CTOs on readmission rates over 12 months in a randomised trial (OCTET). Here, we present follow-up data for a cohort of individuals recruited to our original trial to examine the long-term effect of CTOs on readmissions and the risk of patients disengaging from mental health services temporarily or enduringly. METHODS: For OCTET, an open-label, parallel, randomised controlled trial, we recruited patients aged 18-65 years involuntarily admitted to mental health hospitals in 32 trusts in England, with a diagnosis of psychosis and deemed suitable for CTOs by their clinicians. Between Nov 10, 2008, and Feb 22, 2011, we recruited and randomly assigned 336 eligible patients (1:1) to be discharged on either a CTO (n=167) or to voluntary status via Section 17 leave (control group; n=169). For the analysis presented in this report, we assessed data at 36 months for 330 of these patients. We tested rates of readmission to hospital, time to first readmission, number of readmissions, and duration of readmission in patients assigned to CTO versus those assigned to control, and in all patients with CTO experience at any time in the 36 months versus those without. We also tested whether duration of CTO affected readmission outcomes in patients with CTO experience. We examined discontinuation (>=60 days between clinical contacts) and disengagement from services (no clinical contact for >=90 days with no return to contact) in the whole cohort. OCTET is registered with isrctn.com, number ISRCTN73110773. FINDINGS: We obtained data for 330 patients in the relevant period between Nov 10, 2008 and Feb 22, 2014 (36 months after the last patient was randomly assigned to OCTET). We identified no difference between the randomised groups in the numbers of patients readmitted (100 [61%] of 165 CTOs vs 113 [68%] of 165 controls; relative risk 0.88 [95% CI 0.75-1.03]), number of readmissions (mean 2.4 readmissions [SD 1.91] vs 2.2 [1.43]; incident density ratio [IDR] 0.97 [95% CI 0.76-1.24]), duration of readmissions (median 117.5 days [IQR 63-303] vs 139.5 days [63.0-309.5]; IDR 0.84 [95% CI 0.51-1.38]), or time to first readmission (median 601.0 days [95% CI 387.0-777.0] vs 420.0 days [352.0 548.0]; hazard ratio [HR] 0.81 [95% CI 0.62-1.06]). The CTO experience group had significantly more readmissions than the group without (IDR 1.39 [95% CI 1.07 1.79]) and we noted no significant difference between groups in readmission rates, duration of readmission, or time to first readmission. We did not identify a linear relationship between readmission outcomes and duration of CTO. 19 (6%) patients disengaged from services (12 [7%] of 165 CTOs vs 7 [4%] of 165 controls). Longer duration of compulsion was associated with later disengagement (HR 0.946 [95% CI 0.90-0.99, p=0.023). 187 (57%) experienced no discontinuities, and we noted no significant difference between the CTO and control groups for time to disengagement or number of discontinuities. Levels of discontinuity were associated with compulsion (IDR 0.973 [95% CI 0.96-0.99, p<0.0001]. We identified no effect of baseline characteristics on the associations between compulsion and disengagement. INTERPRETATION: We identified no evidence that increased compulsion leads to improved readmission outcomes or to disengagement from services in patients with psychosis over 36 months. The level of persisting clinical follow-up was much higher than expected, irrespective of CTO status, and could partly account for the absence of CTO effect. The findings from our 36 month follow-up support our original findings that CTOs do not provide patient benefits, and the continued high level of their use should be reviewed. FUNDING: National Institute for Health Research. PMID- 26362498 TI - In vitro inhibition of AKR1Cs by sulphonylureas and the structural basis. AB - Recent epidemiological studies show conflicting data for the first-line anti diabetic sulphonylureas drugs in treating cancer progression in type II diabetes patients. How sulphonylureas promote or diminish tumor growth is not fully understood. Here, we report that seven sulphonylureas exhibit different in vitro inhibition towards AKR1Cs (AKR1C1, AKR1C2, AKR1C3), which are critical steroid hormone metabolism enzymes that are related to prostate cancer, breast cancer and endometrial diseases. Interactions of the sulphonylureas and AKR1Cs were analyzed by X-ray crystallography. PMID- 26362499 TI - Canavanine activates imidazoline I-2 receptors to reduce hyperglycemia in type 1 like diabetic rats. AB - Canavanine is a guanidinium derivative that has the basic structure of a ligand for the imidazoline receptor (I-R). Furthermore, canavanine is found in an herb that has been shown to improve diabetic disorders. Thus, the present study was designed to investigate the anti-hyperglycemic action of canavanine in rats with streptozotocin (STZ)-induced type 1-like diabetes. Canavanine decreased hyperglycemia in the STZ-induced diabetic rats, and this action was blocked by the antagonist specific to imidazoline I-2 receptors (I-2R), BU224, in a dose dependent manner. Additionally, canavanine increased the plasma beta-endorphin level, as measured using enzyme-linked immunosorbent assay (ELISA), and this increase was also blocked by BU224 in the same manner. Moreover, amiloride at a dose sufficient to block I-2AR attenuated the actions of canavanine, including the increased beta-endorphin level and the antihyperglycemic effect. Otherwise, canavanine increased the radioactive glucose uptake into skeletal muscles isolated from the diabetic rats. Furthermore, canavanine increased the phosphorylation of AMPK measured using Western blot analysis in these isolated skeletal muscles in a dose-dependent manner. Additionally, the insulin sensitivity of the diabetic rats was markedly increased by canavanine, and this action was also blocked by BU224. Overall, canavanine is capable of activating imidazoline I-2R; I-2AR is linked to an increase in the plasma level of beta endorphin, and I-2BR is related to effects on the glucose uptake by skeletal muscle that reduces hyperglycemia in type 1-like diabetic rats. Therefore, canavanine can be developed as effective agent to treat the diabetic disorders in the future. PMID- 26362500 TI - Cadmium induces the activation of cell wall integrity pathway in budding yeast. AB - MAP kinases are important signaling molecules regulating cell survival, proliferation and differentiation, and can be activated by cadmium stress. In this study, we demonstrate that cadmium induces phosphorylation of the yeast cell wall integrity (CWI) pathway_MAP kinase Slt2, and this cadmium-induced CWI activation is mediated by the cell surface sensor Mid2 through the GEF Rom1, the central regulator Rho1 and Bck1. Nevertheless, cadmium stress does not affect the subcellular localization of Slt2 proteins. In addition, this cadmium-induced CWI activation is independent on the calcium/calcineurin signaling and the high osmolarity glycerol (HOG) signaling pathways in yeast cells. Furthermore, we tested the cadmium sensitivity of 42 paired double-gene deletion mutants between six CWI components and seven components of the HOG pathway. Our results indicate that the CWI pathway is epistatic to the HOG pathway in cadmium sensitivity. However, gene deletion mutations for the Swi4/Swi6 transcription factor complex show synergistic effects with mutations of HOG components in cadmium sensitivity. PMID- 26362501 TI - Significance of investigating allelopathic interactions of marine organisms in the discovery and development of cytotoxic compounds. AB - Marine sessile organisms often inhabit rocky substrata, which are crowded by other sessile organisms. They acquire living space via growth interactions and/or by allelopathy. They are known to secrete toxic compounds having multiple roles. These compounds have been explored for their possible applications in cancer chemotherapy, because of their ability to kill rapidly dividing cells of competitor organisms. As compared to the therapeutic applications of these compounds, their possible ecological role in competition for space has received little attention. To select the potential candidate organisms for the isolation of lead cytotoxic molecules, it is important to understand their chemical ecology with special emphasis on their allelopathic interactions with their competitors. Knowledge of the ecological role of allelopathic compounds will contribute significantly to an understanding of their natural variability and help us to plan effective and sustainable wild harvests to obtain novel cytotoxic chemicals. This review highlights the significance of studying allelopathic interactions of marine invertebrates in the discovery of cytotoxic compounds, by selecting sponge as a model organism. PMID- 26362502 TI - Proapoptotic activity and ABCC1-related multidrug resistance reduction ability of semisynthetic oleanolic acid derivatives DIOXOL and HIMOXOL in human acute promyelocytic leukemia cells. AB - One of the main problems of present-day oncology is the ability of neoplastic cells to develop different mechanisms of resistance to chemotherapeutic agent. A natural compound oleanolic acid (OA) was found to be active against many types of neoplastic cells. This paper examines the influence of eight semisynthetic oleanolic acid derivatives on drug-sensitive human acute promyelocytic leukemia cell line HL-60 and its multidrug resistant subline ABCC1 overexpressing HL 60/AR. Viability inhibition, proapoptotic activity, as well as influence on the ABCC1 gene expression level, ability to inhibit the transport function of multidrug resistance associated protein 1 (ABCC1) and to alter its level by the tested compounds, were evaluated. The most potent compounds were DIOXOL (methyl 3,11-dioxoolean-12-en-28-oate) and HIMOXOL (methyl 3-hydroxyimino-11-oxoolean-12 en-28-oate). DIOXOL was most efficient in inducing apoptosis of HL-60 cells. It activated both intrinsic and extrinsic pathways of apoptotic cell death. Proapoptotic properties of DIOXOL were probably related to the significant decrease of p65 NFkappaB level and inhibition of its translocation to the nucleus. In turn, HIMOXOL was the most potent compound against resistant HL-60/AR cells. It inhibited ABCC1 transport function (short time response) and decreased the level of ABCC1 protein (long time response) as a result of reduction of ABCC1 expression. PMID- 26362503 TI - On behalf of tradition: An analysis of medical student and physician beliefs on how anatomy should be taught. AB - Human anatomy, one of the basic medical sciences, is a time-honored discipline. As such, it is taught using traditional methods, cadaveric dissection chief among them. Medical imaging has recently gained popularity as a teaching method in anatomy courses. In light of a general tendency to reduce course hours, this has resulted in a decrease of dissection time and intense debates between traditional and modern approaches to anatomy teaching. In an attempt to explore trends in the attitudes of medical professionals toward the various methods of anatomy teaching, medical imaging in particular, the authors constructed a questionnaire and conducted a nationwide survey among medical students (in all stages at medical school), residents, and specialists in all fields of medicine. The survey results demonstrated indisputable appreciation of traditional methods of anatomy teaching, particularly cadaveric dissection, and showed that specialists believe significantly more strongly than clinical or preclinical students that anatomy and medical imaging should be taught separately. Strong correlations among the components of the traditional approach to anatomy instruction were also found. In light of the results, it was recommended that imaging should be incorporated into anatomy courses with caution, and, as far as possible, not at the expense of dissection time. It was advised that medical imaging has to be taught as a separate course, parallel to a traditional anatomy course. This will allow anatomical principles to be appreciated, which in turn will serve the students when they study radiology. "And we proceed in the following order: in front walks Nikolai with the slides or atlases, I come after him, and after me, his head humbly lowered, strides the cart horse; or else, if necessary, a cadaver is carried in first, after the cadaver walks Nikolai, and so on. At my appearance, the students rise, then sit down, and the murmur of the sea suddenly grows still. Calm ensues." -From "A Boring Story: From the Notebook of an Old Man" by Anton Chekhov. PMID- 26362505 TI - Histological analysis of loaded zirconia and titanium dental implants: an experimental study in the dog mandible. AB - OBJECTIVE: To assess whether or not peri-implant soft tissue dimensions and hard tissue integration of loaded zirconia implants are similar to those of a titanium implant. MATERIALS AND METHODS: In six dogs, two one-piece zirconia implants (VC, ZD), a two-piece zirconia implant (BPI) and a control one-piece titanium implant (STM) were randomly placed. CAD/CAM crowns were cemented at 6 months. Six months later, animals were killed and histomorphometric analyses were performed, including: the level of the mucosal margin, the extent of the peri-implant mucosa, the marginal bone loss and the bone-to-implant contact (BIC). Means of outcomes variables were calculated together with their corresponding 95% confidence intervals. RESULTS: In general, the mucosal margin was located coronally to the implant shoulder. The buccal peri-implant mucosa ranged between 2.64 +/- 0.70 mm (VC) and 3.03 +/- 1.71 mm (ZD) (for all median comparisons p > 0.05). The relative marginal bone loss ranged between 0.65 +/- 0.61 mm (BPI) and 1.73 +/- 1.68 mm (ZD) (buccal side), and between 0.55 +/- 0.37 mm (VC) and 1.69 +/- 1.56 mm (ZD) (lingual side) (p > 0.05). The mean BIC ranged between 78.6% +/- 17.3% (ZD) and 87.9% +/- 13.6% (STM) without statistically significant differences between the groups (p > 0.05). CONCLUSIONS: One- and two-piece zirconia rendered similar peri-implant soft tissue dimensions and osseointegration compared to titanium implants that were placed at 6 months of loading. Zirconia implants, however, exhibited a relatively high fracture rate. PMID- 26362504 TI - p53 controls colorectal cancer cell invasion by inhibiting the NF-kappaB-mediated activation of Fascin. AB - p53 mutation is known to contribute to cancer progression. Fascin is an actin bundling protein and has been recently identified to promote cancer cell migration and invasion through its role in formation of cellular protrusions such as filopodia and invadopodia. However, the relationship between p53 and Fascin is not understood. Here, we have found a new link between them. In colorectal adenocarcinomas, p53 mutation correlated with high NF-kappaB, Fascin and low E cadherin expression. Moreover, this expression profile was shown to contribute to poor overall survival in patients with colorectal cancer. Wild-type p53 could inhibit NF-kappaB activity that repressed the expression of Fascin and cancer cell invasiveness. In contrast, in p53-deficient primary cultured cells, NF kappaB activity was enhanced and then activation of NF-kappaB increased the expression of Fascin. In further analysis, we showed that NF-kappaB was a key determinant for p53 deletion-stimulated Fascin expression. Inhibition of NF kappaB/p65 expression by pharmacological compound or p65 siRNA suppressed Fascin activity in p53-deficient cells. Moreover, restoration of p53 expression decreased the activation of Fascin through suppression of the NF-kappaB pathway. Taken together, these data suggest that a negative-feedback loop exists, whereby p53 can suppress colorectal cancer cell invasion by inhibiting the NF-kappaB mediated activation of Fascin. PMID- 26362506 TI - The Clinical Usefulness of Sleep Studies in Children. AB - Sleep disordered breathing is common in children and has the potential to have a significant impact on cognition, activity and social interaction. The overnight in-laboratory polysomnography (PSG) continues to be the gold standard instrument for the investigation of sleep-disordered breathing in children. It has the ability to rule in or rule out the need for intervention for common conditions such as obstructive sleep apnoea, assess the role of sleep quality in children and adolescents with hypersomnolence, provide physiologic data in children with hypoventilation as may be seen in neuromuscular disease and assist in the assessment of children with structural airway and lung abnormalities. Polysomnography is valuable and the only reliable method to differentiate habitual snoring from many levels of sleep apnoea syndrome [1]. The American Academy of Paediatrics recommends that, in order to diagnose and manage OSA syndrome, all children should be screened for snoring and complex cases should be referred to a specialist. PSG is the diagnostic gold standard and adenotonsillectomy is the first line of treatment [2]. There is no evidence to support nap studies or ambulatory sleep studies in children [3]. With adequate staffing, expertise, and a child and family-friendly environment, children of any age can undergo a sleep study. PMID- 26362507 TI - Diagnostic Methods in Primary Ciliary Dyskinesia. AB - Diagnosing primary ciliary dyskinesia is difficult. With no reference standard, a combination of tests is needed; most tests require expensive equipment and specialist scientists. We review the advances in diagnostic testing over the past hundred years, with emphasis on recent advances. We particularly focus on use of high-speed video analysis, transmission electron microscopy, nasal nitric oxide and genetic testing. We discuss the international efforts that are in place to advance the evidence base for diagnostic tests. PMID- 26362508 TI - Biokinetics in repeated-dosing in vitro drug toxicity studies. AB - The aim of the EU FP7 Predict-IV project was to improve the predictivity of in vitro assays for unwanted effects of drugs after repeated dosing. The project assessed the added benefit of integrating long-lived in vitro organotypic cell systems with 'omics' technologies and in silico modelling, including systems biology and pharmacokinetic assessments. RPTEC/TERT1 kidney cells, primary rat and human hepatocytes, HepaRG liver cells and 2D and 3D primary brain cultures were dosed daily or every other day for 14 days to a selection of drugs varying in their mechanism of pharmacological action. Since concentration-effect relationships not only depend on the activity of the drug or the sensitivity of the target, but also on the distribution of compounds in the in vitro system, the concentration of a selection of drugs in cells, microtitre plate plastic and medium was measured over time. Results, reviewed in this paper, indicate that lipophilic drugs bind significantly to plastic labware. A few drugs, including less lipophilic drugs, bind to cell-attachment matrices. Chemicals that reach high concentrations in cells, including cyclosporin A and amiodarone, significantly accumulate over time after repeated dosing, partly explaining their increased toxicity after repeated dosing, compared to a single dose. PMID- 26362509 TI - Assessment of the eye irritation potential of chemicals: A comparison study between two test methods based on human 3D hemi-cornea models. AB - We have recently developed two hemi-cornea models (Bartok et al., Toxicol in Vitro 29, 72, 2015; Zorn-Kruppa et al. PLoS One 9, e114181, 2014), which allow the correct prediction of eye irritation potential of chemicals according to the United Nations globally harmonized system of classification and labeling of chemicals (UN GHS). Both models comprise a multilayered epithelium and a stroma with embedded keratocytes in a collagenous matrix. These two models were compared, using a set of fourteen test chemicals. Their effects after 10 and 60 minutes (min) exposure were assessed from the quantification of cell viability using the MTT reduction assay. The first approach separately quantifies the damage inflicted to the epithelium and the stroma. The second approach quantifies the depth of injury by recording cell death as a function of depth. The classification obtained by the two models was compared to the Draize rabbit eye test and an ex vivo model using rabbit cornea (Jester et al. Toxicol in Vitro. 24, 597-604, 2010). With a 60 min exposure, both of our models are able to clearly differentiate UN GHS Category 1 and UN GHS Category 2 test chemicals. PMID- 26362510 TI - Low-concentration uranium enters the HepG2 cell nucleus rapidly and induces cell stress response. AB - This study aimed to compare the cell stress effects of low and high uranium concentrations and relate them to its localization, precipitate formation, and exposure time. The time-course analysis shows that uranium appears in cell nuclei as a soluble form within 5 min of exposure, and quickly induces expression of antioxidant and DNA repair genes. On the other hand, precipitate formations began at the very beginning of exposure at the 300-MUM concentration, but took longer to appear at lower concentrations. Adaptive response might occur at low concentrations but are overwhelmed at high concentrations, especially when uranium precipitates are abundant. PMID- 26362511 TI - The Walking Interventions Through Texting (WalkIT) Trial: Rationale, Design, and Protocol for a Factorial Randomized Controlled Trial of Adaptive Interventions for Overweight and Obese, Inactive Adults. AB - BACKGROUND: Walking is a widely accepted and frequently targeted health promotion approach to increase physical activity (PA). Interventions to increase PA have produced only small improvements. Stronger and more potent behavioral intervention components are needed to increase time spent in PA, improve cardiometabolic risk markers, and optimize health. OBJECTIVE: Our aim is to present the rationale and methods from the WalkIT Trial, a 4-month factorial randomized controlled trial (RCT) in inactive, overweight/obese adults. The main purpose of the study was to evaluate whether intensive adaptive components result in greater improvements to adults' PA compared to the static intervention components. METHODS: Participants enrolled in a 2x2 factorial RCT and were assigned to one of four semi-automated, text message-based walking interventions. Experimental components included adaptive versus static steps/day goals, and immediate versus delayed reinforcement. Principles of percentile shaping and behavioral economics were used to operationalize experimental components. A Fitbit Zip measured the main outcome: participants' daily physical activity (steps and cadence) over the 4-month duration of the study. Secondary outcomes included self-reported PA, psychosocial outcomes, aerobic fitness, and cardiorespiratory risk factors assessed pre/post in a laboratory setting. Participants were recruited through email listservs and websites affiliated with the university campus, community businesses and local government, social groups, and social media advertising. RESULTS: This study has completed data collection as of December 2014, but data cleaning and preliminary analyses are still in progress. We expect to complete analysis of the main outcomes in late 2015 to early 2016. CONCLUSIONS: The Walking Interventions through Texting (WalkIT) Trial will further the understanding of theory-based intervention components to increase the PA of men and women who are healthy, insufficiently active and are overweight or obese. WalkIT is one of the first studies focusing on the individual components of combined goal setting and reward structures in a factorial design to increase walking. The trial is expected to produce results useful to future research interventions and perhaps industry initiatives, primarily focused on mHealth, goal setting, and those looking to promote behavior change through performance-based incentives. TRIAL REGISTRATION: ClinicalTrials.gov NCT02053259; https://clinicaltrials.gov/ct2/show/NCT02053259 (Archived by WebCite at http://www.webcitation.org/6b65xLvmg). PMID- 26362512 TI - [Incidental finding of an abdominal secreting paraganglioma: A case report]. PMID- 26362513 TI - [Complete remission under azathioprine in a corticoresistant case of Cogan's syndrome]. PMID- 26362514 TI - [Idiopathic non-cirrhotic portal hypertension: An update]. AB - Idiopathic non-cirrhotic portal hypertension is an under-estimated cause of portal hypertension. The diagnosis requires the exclusion of cirrhosis, common causes of chronic liver disease and venous obstruction of the portal and hepatic veins. It has been associated with various extra-hepatic conditions that are most frequently immunologic, prothrombotic, hematologic and toxic. The most frequent clinical complications are variceal hemorrhage and portal vein thrombosis. Complications of portal hypertension should be managed as in patients with cirrhosis. PMID- 26362515 TI - [On intoxication alphachloralose to addiction]. PMID- 26362516 TI - A model for activation of the hexadecameric phosphorylase kinase complex deduced from zero-length oxidative crosslinking. AB - Phosphorylase kinase (PhK) is a hexadecameric (alphabetagammadelta)(4) enzyme complex that upon activation by phosphorylation stimulates glycogenolysis. Due to its large size (1.3 MDa), elucidating the structural changes associated with the activation of PhK has been challenging, although phosphoactivation has been linked with an increased tendency of the enzyme's regulatory beta-subunits to self-associate. Here we report the effect of a peptide mimetic of the phosphoryltable N-termini of beta on the selective, zero-length, oxidative crosslinking of these regulatory subunits to form beta-beta dimers in the nonactivated PhK complex. This peptide stimulated beta-beta dimer formation when not phosphorylated, but was considerably less effective in its phosphorylated form. Because this peptide mimetic of beta competes with its counterpart region in the nonactivated enzyme complex in binding to the catalytic gamma-subunit, we were able to formulate a structural model for the phosphoactivation of PhK. In this model, the nonactivated state of PhK is maintained by the interaction between the nonphosphorylated N-termini of beta and the regulatory C-terminal domains of the gamma-subunits; phosphorylation of beta weakens this interaction, leading to activation of the gamma-subunits. PMID- 26362517 TI - [Antibiotic resistance of community-acquired uropathogenic Enterobacteriaceae isolated in Sfax (Tunisia)]. PMID- 26362518 TI - Behavioral and pharmacological characteristics of bortezomib-induced peripheral neuropathy in rats. AB - Bortezomib, an effective anticancer drug for multiple myeloma, often causes peripheral neuropathy which is mainly characterized by numbness and painful paresthesia. Nevertheless, there is no effective strategy to escape or treat bortezomib-induced peripheral neuropathy (BIPN), because we have understood few mechanism of this side effect. In this study, we evaluated behavioral and pathological characteristics of BIPN, and investigated pharmacological efficacy of various analgesic drugs and adjuvants on mechanical allodynia induced by bortezomib treatment in rats. The repeated administration of bortezomib induced mechanical and cold allodynia. There was axonal degeneration of sciatic nerve behind these neuropathic symptoms. Furthermore, the exposure to bortezomib shortened neurite length in PC12 cells. Finally, the result of evaluation of anti allodynic potency, oral administration of tramadol (10 mg/kg), pregabalin (3 mg/kg), duloxetine (30 mg/kg) or mexiletine (100 mg/kg), but not amitriptyline or diclofenac, transiently relieved the mechanical allodynia induced by bortezomib. These results suggest that axonal degeneration of the sciatic nerve is involved in BIPN and that some analgesic drugs and adjuvants are effective in the relief of painful neuropathy. PMID- 26362519 TI - (Pro)renin Receptor Blockade Ameliorates Cardiac Injury and Remodeling and Improves Function After Myocardial Infarction. AB - BACKGROUND: The (pro)renin receptor [(P)RR] is implicated in the pathogenesis of cardiovascular disease. We investigated the effects of (P)RR blockade after myocardial infarction (MI) in a mouse coronary-ligation model. METHODS AND RESULTS: Mice underwent sham control surgeries (n = 8) or induction of MI followed by 28 days' treatment with a vehicle control (n = 8) or (P)RR antagonist (n = 8). Compared with sham control subjects, MI + vehicle mice demonstrated reduced left ventricular (LV) ejection fraction (LVEF: P < .001) and fractional shortening (P < .001), and increased LV end-systolic and -diastolic volumes (LVESV: P < .001; LVEDV: P < .001) 28 days after MI. In addition, MI decreased LV posterior wall and septal diameters (both P < .001), increased heart weight-body weight ratios (P < .05), LV collagen deposition, and cardiomyocyte diameter (both P < .001), and up-regulated collagen 1 (P < .01) and beta-myosin heavy chain (beta-MHC: P < .05) mRNA. Compared with MI + vehicle mice, (P)RR antagonism after MI reduced infarct size (P < .01), improved LVEF (P < .001), fractional shortening (P < .001), and stroke volume (P < .05), and decreased LVESV (P < .001) and LVEDV (P < .001). (P)RR antagonism also reversed MI-induced transmural thinning (P < .001) and reduced LV fibrosis (P < .01), cardiomyocyte size (P < .001), and ventricular collagen 1 (P < .01), beta-MHC (P = .06), transforming growth factor beta1 (P < .01), and angiotensin-converting enzyme (P < .05) expression. CONCLUSIONS: The present study found that (P)RR blockade after MI in mice ameliorates infarct size, cardiac fibrosis/hypertrophy, and cardiac dysfunction and identifies the receptor as a potential therapeutic target in this setting. PMID- 26362520 TI - Activities and Compensation of Advanced Heart Failure Specialists: Results of the Heart Failure Society of America (HFSA) Survey. AB - BACKGROUND: In the current era, where advanced heart failure (AHF) has become an American Board of Internal Medicine-certified subspecialty, new data are needed to benchmark and value levels of clinical effort performed by AHF specialists (AHFMDs). METHODS AND RESULTS: A 36-question survey was sent to 728 AHFMDs, members of the Heart Failure Society of America, and 224 (31%) responded. Overall, 56% worked in academic medical centers (AMCs) and were younger (48 +/- 9 y vs 52 +/- 10 y; P < .01) and were represented by a higher proportion of women (34% vs 21%, P < .01) compared with non-AMCs. The percentage of time in clinical care was lower in AMCs (64 +/- 19% vs 78 +/- 18%; P = .002), with similar concentration on evaluation and management services (79 +/- 18% in AMCs vs 72 +/- 18 % in non-AMCs; P = NS). The majority of nonclinical time was spent in program administration (10% in both AMCs and non-AMCs) and education/research (15% in AMC vs 5% in non-AMCs). Although 69% of respondents were compensated by work-relative value units (wRVUs), only a small percentage knew their target or the amount of RVUs generated. The mean annual wRVUs generated were lower in AMCs compared to non-AMCs (5,452 +/- 1,961 vs 9,071 +/- 3,484; P < .001). The annual compensation in AMCs was lower than in non-AMCs (45% vs 10% <$250,000 and 17% vs 61% >$350,000; P < .001) and the satisfaction with compensation was higher in non AMCs. CONCLUSIONS: AHFMDs' compensation is largely dependent by practice type (AMC vs non-AMC) and clinical productivity as measured by wRVUs. These data provide an opportunity for benchmarking work effort and compensation for AHFMDs, allowing distinction from segments of cardiologists with greater opportunity to accrue procedural wRVUs. They also show several differences between AMCs and non AMCs that should be considered when formulating work assignment and compensation for AHFMDs. PMID- 26362521 TI - A Reminiscence about Early Times of Vitreous Water in Electron Cryomicroscopy. PMID- 26362522 TI - Re-examining current breast cancer screening: An analysis of the 2009 U.S. Preventive Services Task Force guidelines for breast cancer screening. AB - The U.S. Preventive Services Task Force (USPSTF) released new mammography screening guidelines in November 2009. The panel's comprehensive review of evidence for this preventive service concluded that the net benefit of screening mammography was too small to justify universal screening for women younger than 50 years of age but advocated continuing universal screening, though biennially rather than annually, for women ages 50-74 years. Under these new recommendations, it is possible undetected early breast cancers may increase and result in increases in breast cancer morbidity. This policy analysis assessed the impact of the new guidelines regarding whether the policy changes have affected breast cancer detection and treatment in the ensuing 5 years, and whether these guidelines may affect morbidity and mortality from breast cancer in the future. Trade-offs are present in cost-effectiveness and earlier detection with better treatment for women ages 40-49 years. Follow-up studies will be crucial to monitor changes in outcome for mortality and surgical intervention and ascertain the full impact of the new guidelines for women younger than 50 years. PMID- 26362523 TI - Correlation between arterial stiffness and coronary flow velocity reserve in subjects with pulse wave velocity >1400 cm/s. AB - Brachial-ankle pulse wave velocity (ba-PWV) is an independent predictor for cardiovascular events. Coronary flow velocity reserve (CFVR) provides important information for coronary endothelial function. In the present study, we investigated the possible relationship between PWV and CFVR, especially in subjects with PWV > 1400 cm/s. Seventy five subjects were divided into two groups based on baPWV value (baPWV > 1400 cm/s versus baPWV < 1400 cm/s). PWV and CFVR were measured by Colin VP-1000 apparatus and non-invasive Doppler echocardiography, respectively. Our results showed that CFVR was significantly lower in patients with baPWV > 1400 cm/s than in patients with baPWV < 1400 cm/s (2.57 +/- 0.68 versus 3.04 +/- 0.73, p < 0.01). baPWV was negatively correlated with CFVR in the entire study group (r = -0.45, p < 0.0001) even adjusting for age, prevalence of diabetes mellitus and systolic blood pressure (r = -0.33, p = 0.044). Moreover, baPWV was markedly negatively correlated with CFVR in patients with baPWV > 1400 cm/s (r = -0.42, p < 0.01). Multiple linear regressions showed that baPWV was independently associated with CFVR in the entire study group (beta = -0.702, p < 0.001). Our results showed that large arterial stiffness was negatively correlated with decreased CFVR especially in subjects with baPWV > 1400 cm/s, and baPWV was independently associated with CFVR. PMID- 26362524 TI - Unravelling the genetic components involved in the immune response of pigs vaccinated against influenza virus. AB - A genome-wide association study for immune response to influenza vaccination in a crossbred swine population was conducted. Swine influenza is caused by influenza A virus (FLUAV) which is considered one of the most prevalent respiratory pathogens in swine worldwide. The main strategy used to control influenza in swine herds is through vaccination. However, the currently circulating FLUAV subtypes in swine are genetically and antigenically diverse and their interaction with the host genetics poses a challenge for the production of efficacious and cross-protective vaccines. In this study, 103 pigs vaccinated with an inactivated H1N1 pandemic virus were genotyped with the Illumina PorcineSNP60V2 BeadChip for the identification of genetic markers associated with immune response efficacy to influenza A virus vaccination. Immune response was measured based on the presence or absence of HA (hemagglutinin) and NP (nucleoprotein) antibodies induced by vaccination and detected in swine sera by the hemagglutination inhibition (HI) and ELISA assays, respectively. The ELISA test was also used as a measurement of antibody levels produced following the FLUAV vaccination. Associations were tested with x(2) test for a case and control data and using maximum likelihood method for the quantitative data, where a moderate association was considered if p<5*10(-5). When testing the association using the HI results, three markers with unknown location and three located on chromosomes SSCX, SSC14 and SSC18 were identified as associated with the immune response. Using the response to vaccination measured by ELISA as a qualitative and quantitative phenotype, four genomic regions were associated with immune response: one on SSC12 and three on chromosomes SSC1, SSC7, and SSC15, respectively. Those regions harbor important functional candidate genes possibly involved with the degree of immune response to vaccination. These results show an important role of host genetics in the immune response to influenza vaccination. Genetic selection for pigs with better response to FLUAV vaccination might be an alternative to reduce the impact of influenza virus infection in the swine industry. However, these results should to be validated in additional populations before its use. PMID- 26362525 TI - Long noncoding RNA: Novel links between gene expression and innate immunity. AB - Protection against infection and maintenance of homeostasis are the hallmarks of the innate immune system. The complex signaling cascades that occur following microbial infection have been studied intensely for a number of years and long noncoding RNA (lncRNA) represent novel regulatory components of these pathways. The catalogue of lncRNA present in our genomes continues to increase as deep sequencing data becomes available. It is clear that they represent critical regulatory steps in a large number of biological systems yet we currently understand the functions for approximately 1% of all annotated lncRNA. This review will cover the recent findings on the emerging roles for lncRNA in controlling the inflammatory response and their mechanisms of action. Gaining a better understanding of these processes could facilitate the development of novel therapeutics to prevent damaging inflammation. PMID- 26362526 TI - Clinician and educator experiences of facilitating students' transition back to school following acquired brain injury: A qualitative systematic review. AB - OBJECTIVE: Transition back to school following paediatric acquired brain injury (ABI) is complex. It must be facilitated by healthcare and educational professionals, who need to work together to return affected students to learning. This qualitative systematic review synthesizes qualitative studies on clinicians' and educators' experiences of facilitating hospital-to-school transitions following ABI. METHODS: A search was conducted using seven electronic databases (CINAHL, Cochrane, EMBASE, ERIC, HealthSTAR, MEDLINE, PsycINFO) and key resources were manually reviewed. Publications selected for inclusion had a sample of clinicians and/or educators who worked with children/youth with ABI and focused on hospital-to-school transition processes from the professionals' perspectives. RESULTS: The initial search returned 4761 publications. Of those, 10 met the inclusion criteria. Six main themes emerged across those publications. Three related to transition barriers: (1) lack of training and education regarding transition processes; (2) lack of communication between stakeholders; and (3) lack of preparation for transition. The remaining three presented items that both facilitate and/or impede the transition process: (4) supports available; (5) linking agents; and (6) policies and procedures guiding transition. CONCLUSIONS: Clinicians and educators called for collaboration and communication to support students' transition back to school. Further inquiry into designated linking agents and policies that facilitate hospital-to-school transitions for students following ABI may address these lacking areas. PMID- 26362527 TI - An improved region growing algorithm for phase correction in MRI. AB - PURPOSE: To develop an improved region-growing algorithm for phase correction in MRI. METHODS: Phase correction in MRI can sometimes be formulated as selecting a vector for each pixel of an image from two candidate vectors so that the orientation of the output is spatially smooth. Existing algorithms may run into difficulty in the presence of high noise, artifacts, or spatially isolated objects. In this study, we developed an improved region-growing algorithm to include the following novel and salient features: 1) automated quality guidance for determining the sequence of region growing, 2) joint consideration of two candidate vectors in selecting the output vector, and 3) automated segmentation during region growing for handling spatially isolated objects. The phase correction algorithm was tested in different body parts of five healthy volunteers at 3.0T and of one healthy volunteer at 1.5T for two-point Dixon water and fat imaging with flexible echo times. RESULTS: The algorithm achieved successful phase correction in all the data sets tested, providing improvement in areas of known difficulty, when compared with an algorithm lacking the new features. CONCLUSION: The improved region-growing algorithm can be used for reliable and robust phase correction even when regions of high noise, artifacts, or spatially isolated objects are present in an image. Magn Reson Med 76:519-529, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26362528 TI - Monoclonal antibodies - A new era in the treatment of multiple myeloma. AB - Monoclonal antibodies (mAbs) are currently the most investigated therapeutic compounds in oncology, but there is no monoclonal antibody approved in the treatment of multiple myeloma (MM). Nevertheless several really promising molecules are under investigation in phase III clinical trials. Dominantly daratumumab (anti-CD38) and elotuzumab (anti-CS1) showed extraordinary effectiveness in phase I/II trials. The toxicity was acceptable which is important for their addition to standard anti-myeloma agents like proteasome inhibitors or immunomodulatory drugs. Monoclonal antibodies such as denosumab (anti-RANKL) or BHQ880 (anti-DKK-1) are investigated also in the management of myeloma bone disease. This review is focused on the most promising mAbs, their mechanisms of action and the rationale of use. Practically all available results have been described. If the ongoing trials confirm the efficacy and safety of mAbs, they would become an important part of MM treatment that would be translated in the further improvement of therapeutic outcomes. PMID- 26362529 TI - Clinical effect of azithromycin as an adjunct to non-surgical treatment of chronic periodontitis: a meta-analysis of randomized controlled clinical trials. AB - The results of recent published studies focusing on the effect of azithromycin as an adjunct to scaling and root planing (SRP) in the treatment of chronic periodontitis are inconsistent. We conducted a meta-analysis of randomized controlled clinical trials to examine the effect of azithromycin combined with SRP on periodontal clinical parameters as compared to SRP alone. An electronic search was carried out on Pubmed, Embase and the Cochrane Central Register of Controlled Trials from their earliest records through December 28, 2014 to identify studies that met pre-stated inclusion criteria. Reference lists of retrieved articles were also reviewed. Data were extracted independently by two authors. Either a fixed- or random-effects model was used to calculate the overall effect sizes of azithromycin on probing depth, attachment level (AL) and bleeding on probing (BOP). Heterogeneity was evaluated using the Q test and I(2) statistic. Publication bias was evaluated by Begg's test and Egger's test. A total of 14 trials were included in the meta-analysis. Compared with SRP alone, locally delivered azithromycin plus SRP statistically significantly reduced probing depth by 0.99 mm (95% CI 0.42-1.57) and increased AL by 1.12 mm (95% CI 0.31-1.92). In addition, systemically administered azithromycin plus SRP statistically significantly reduced probing depth by 0.21 mm (95% CI 0.12-0.29), BOP by 4.50% (95% CI 1.45-7.56) and increased AL by 0.23 mm (95% CI 0.07-0.39). Sensitivity analysis yielded similar results. No evidence of publication bias was observed. The additional benefit of systemic azithromycin was shown at the initially deep probing depth sites, but not at shallow or moderate sites. The overall effect sizes of systemic azithromycin showed a tendency to decrease with time, and meta-regression analysis suggested a negative relation between the length of follow-up and net change in probing depth (r = -0.05, p = 0.02). This meta-analysis provides further evidence that azithromycin used as an adjunct to SRP significantly improves the efficacy of non-surgical periodontal therapy on reducing probing depth, BOP and improving AL, particularly at the initially deep probing depth sites. PMID- 26362530 TI - Potential for beneficial application of sulfate reducing bacteria in sulfate containing domestic wastewater treatment. AB - The activity of sulfate reducing bacteria (SRB) in domestic wastewater treatment plants (WWTP) is often considered as a problem due to H2S formation and potential related odour and corrosion of materials. However, when controlled well, these bacteria can be effectively used in a positive manner for the treatment of wastewater. The main advantages of using SRB in wastewater treatment are: (1) minimal sludge production, (2) reduction of potential pathogens presence, (3) removal of heavy metals and (4) as pre-treatment of anaerobic digestion. These advantages are accessory to efficient and stable COD removal by SRB. Though only a few studies have been conducted on SRB treatment of domestic wastewater, the many studies performed on industrial wastewater provide information on the potential of SRB in domestic wastewater treatment. A key-parameter analyses literature study comprising pH, organic substrates, sulfate, salt, temperature and oxygen revealed that the conditions are well suited for the application of SRB in domestic wastewater treatment. Since the application of SRB in WWTP has environmental benefits its application is worth considering for wastewater treatment, when sulfate is present in the influent. PMID- 26362531 TI - Preeclampsia: Syndrome or Disease? AB - The focus on disease mechanisms underlying the hypertension and proteinuria defining preeclampsia has increased knowledge of the pathophysiology yet we lack both therapy and predictors. We propose this is in part due to the fact that diagnostic findings identify a "preeclampsia syndrome" but do not necessarily indicate the most important pathophysiology nor if organs are involved as cause or consequence. The increased risk for later life cardiovascular disease in women who develop preeclampsia suggests the stress test of pregnancy exposes pre existing subclinical vascular disease. The dogma that inadequate trophoblast invasion and ischemia/reperfusion injury to the placenta is "the" cause of preeclampsia is more relevant to early onset preeclampsia (<34 weeks). There is much less evidence for defective placentation in late onset preeclampsia where maternal constitutive factors or susceptibility to vascular damage is more relevant. The contribution of differing disease phenotypes to the syndrome may explain the inability of biomarker studies to identify all preeclampsia. Identification of phenotypes will require large amounts of prospective clinical data and biospecimens, collected in a harmonized manner with analysis in an unbiased discovery approach. PMID- 26362532 TI - Phylogeographic analysis of Japanese encephalitis virus in India (1956-2012). AB - Japanese encephalitis virus (JEV) isolates from India phylogenetically belong to two genotypes, III and I. We used envelope gene sequences from GenBank, representing different states of India and other countries, to study the spatiotemporal transmission histories of these two JEV genotypes separately. Genotype III was found to have been successively introduced in the 1930s, 1950s and 1960s, followed by genotype I twice around 2003-2006. Changes in JEV disease patterns in India over the last five decades could thus be attributed to multiple introductions of JEV strains from neighboring Asian countries along with increased transmission potential due to altered ecological settings. PMID- 26362533 TI - "Picking up the pieces" - Meanings of receiving home nursing care when being old and living with advanced cancer in a rural area. AB - Rural home nursing care is a neglected area in the research of palliative care offered to older cancer patients. Because access to specialized services is hampered by long distances and fragmented infrastructure, palliative care is often provided through standard home nursing services and delivered by general district nurses. This study aimed to illuminate the lived experience and to interpret the meaning of receiving home nursing care when being old and living with advanced cancer in a rural area in Norway. Narrative interviews were conducted with nine older persons, and a phenomenological hermeneutic approach was used to interpret the meaning of the lived experience. The analysis revealed three themes, each with subthemes: being content with what one gets, falling into place, and losing one's place. The phrase picking up the pieces was found useful to sum up the meaning of this lived experience. The three respective themes refer to how the pieces symbolize the remaining parts of life or available services in their environment, and how the older persons may see themselves as pieces or bricks in a puzzle. A strong place attachment (physical insideness, social insideness, and autobiographical insideness) is demonstrated by the informants in this study and suggests that the rural context may provide an advantageous healthcare environment. Its potential to be a source of comfort, security, and identity concurs with cancer patients' strong desire for being seen as unique persons. The study shows that district nurses play an essential role in the provision of palliative care for older rural patients. However, the therapeutic value of being in one's familiar landscape seems to depend on how homecare nurses manage to locate it and use it in a more or less person-centred manner. Communication skills and attentiveness to psychosocial aspects of patient care stand out as important attributes for nursing in this context. PMID- 26362534 TI - Simple scoring system for prediction of mortality in Fournier's gangrene. AB - PURPOSE: To create new scoring system for prediction of hospital mortality for patients with Fournier's gangrene(FG). MATERIAL AND METHOD: In total, 84 patients with FG were enrolled into this study. The demographic and clinical characteristics of patients were analyzed retrospectively. RESULTS: The mortality rate was 11.9 %. On multivariate analyses, age >60 years, BUN >40 mg/dl, RDW >14.95 %, albumin level <20 mg/dl and presence of sepsis were significant and independent predictors of mortality. The predictive value of our score for mortality was 95.1 %. CONCLUSION: Our scoring system shows adequate discriminatory function for prediction of mortality in patients with FG. Further larger scale studies can improve the performance of our score. PMID- 26362535 TI - The impact of increased plasma ratios in massively transfused trauma patients: a prospective analysis. AB - PURPOSE: Transfusion ratios approaching 1:1 FFP:PRBC for trauma resuscitation have become the de facto standard of care. The aim of this study was to prospectively evaluate the effect of increasing ratios of FFP:PRBC transfusion on survival for massively transfused civilian trauma patients as well as determine if time to reach the target ratio had any effect on outcomes. METHODS: This is a prospective, observational study of all trauma patients requiring a massive transfusion (>=10 PRBC in <=24 h) at a level 1 trauma center over a 2.5-year period. The ratio of FFP:PRBC was tracked hourly up to 24 h post-initiation of massive transfusion. A logistic regression model was utilized to identify the ideal ratio associated with mortality prediction. A stepwise logistic regression was performed to identify independent predictors of mortality. RESULTS: The study population was predominantly male (89 %) with a mean age of 34.8 +/- 16. On admission, 22 % had a systolic blood pressure <=90 mmHg, 47 % had a heart rate >=120, and 25 % had a GCS <=8. The overall mortality was 33 %. The ratio of FFP:PRBC >= 1:1.5 was the second most important independent predictor of mortality for this population (R (2) = 0.59). Survivors had a higher FFP:PRBC ratio at all times during the first 24 h of resuscitation. CONCLUSIONS: Achieving a ratio of FFP:PRBC >= 1:1.5 after the initial 24 h of resuscitation significantly improves survival in massively transfused trauma patients compared to patients that achieved a ratio <1:1.5. PMID- 26362536 TI - Proteomic analysis of HIV-1 Gag interacting partners using proximity-dependent biotinylation. AB - BACKGROUND: The human immunodeficiency virus type 1 (HIV-1) Gag polyprotein is necessary and sufficient to assemble non-infectious particles. Given that HIV-1 subverts many host proteins at all stages of its life cycle, it is essential to identify these interactions as potential targets for antiretroviral therapy. FINDINGS: This work demonstrates the use of proximity-dependent biotin identification (BioID) of host proteins and complexes that are proximal to the N terminal domains of the HIV-1 Gag polyprotein. Two of the hits identified in the BioID screen were validated by immunoprecipation and confirmed the interaction of DDX17 and RPS6 with HIV-1 Gag. CONCLUSIONS: Our results show that BioID is both a successful and complementary method to screen for nearby interacting proteins of HIV-1 Gag during the replicative cycle in different cell lines. PMID- 26362539 TI - Effects of Performance Versus Game-Based Mobile Applications on Response to Exercise. AB - BACKGROUND: Given the popularity of mobile applications (apps) designed to increase exercise participation, it is important to understand their effects on psychological predictors of exercise behavior. PURPOSE: This study tested a performance feedback-based app compared to a game-based app to examine their effects on aspects of immediate response to an exercise bout. METHODS: Twenty eight participants completed a 30-min treadmill run while using one of two randomly assigned mobile running apps: Nike + Running, a performance-monitoring app which theoretically induces an associative, goal-driven state, or Zombies Run!, an app which turns the experience of running into a virtual reality game, theoretically inducing dissociation from primary exercise goals. RESULTS: The two conditions did not differ on primary motivational state outcomes; however, participants reported more associative attentional focus in the performance monitoring app condition compared to more dissociative focus in the game-based app condition. CONCLUSIONS: Game-based and performance-tracking running apps may not have differential effects on goal motivation during exercise. However, game based apps may help recreational exercisers dissociate from exercise more readily. Increasing the enjoyment of an exercise bout through the development of new and innovative mobile technologies is an important avenue for future research. PMID- 26362537 TI - Diagnostic accuracy and prognostic utility of D Dimer in acute appendicitis in children. AB - The objective was to determine the uselfulness of D Dimer (DD) as a diagnostic or prognostic marker in acute appendicitis (AA) in children using a prospective observational study in the pediatric emergency department of a tertiary hospital. We enrolled 135 patients aged 1-16 years presenting with abdominal pain consistent with AA, who required laboratory studies. We analyzed clinical, analytical variables and histopathology findings (when they underwent surgery). Statistical analysis was conducted using SPSS. 38.5% of the children were clinically diagnosed with AA (n = 52), confirmed by pathology in 51 patients. 55.8% were gangrenous appendicitis. Leucocyte count, C-reactive protein (CRP), and DD were higher in the AA group and in the gangrenous appendicitis group (p < 0.05), with highest values of DD in the gangrenous group. The area under the receiving operating characteristics (ROC) curve for DD in the diagnosis of AA is 0.66 (95% CI 0.56-0.75). For DD cut-off point of 230 ng/mL, sensitivity (Se) was 0.40, specificity (Sp) 0.80, positive predictive value (PPV) 0.57, and negative predictive value (NPV) 0.66. The area under the ROC curve for DD in children with gangrenous appendicitis is 0.93 (95% CI 0.87-1). A DD cut-off point of 230 ng/mL exhibited: Se = 0.69, Sp = 1, PPV = 1 and NPV = 0.72. CONCLUSION: DD levels increase in patients with AA. Although it does not constitute a useful diagnostic marker, it could be a good prognostic marker. PMID- 26362538 TI - Expert consensus statement 'Neonatologist-performed Echocardiography (NoPE)' training and accreditation in UK. AB - Targeted echocardiographic assessments of haemodynamic status are increasingly utilised in many settings. Application in the neonatal intensive care units (NICU) is increasingly demanded but challenging given the risk of underlying structural lesions. This statement follows discussions in UK led by the Neonatologists with an Interest in Cardiology and Haemodynamics (NICHe) group in collaboration with the British Congenital Cardiac Association (BCCA) and the Paediatricians with Expertise in Cardiology Special Interest Group (PECSIG). Clear consensus was agreed on multiple aspects of best practice for neonatologist performed echocardiogram (NoPE)-rigorous attention to infection control and cardiorespiratory/thermal stability, early referral to paediatric cardiology with suspicion of structural disease, reporting on standardised templates, reliable image storage, regular skills maintenance, collaboration with a designated paediatric cardiologist, and regular scan audit/review. It was agreed that NoPE assessments should confidently exclude structural lesions at first scan. Practitioners would be expected to screen and establish gross normality of structure at first scan and obtain confirmation from paediatric cardiologist if required, and subsequently, functional echocardiography can be performed for haemodynamic assessment to guide management of newborn babies. To achieve training, NICHe group suggested that mandatory placements could be undertaken during core registrar training or neonatal subspecialty grid training with a paediatric cardiology placement for 6 months and a neonatology placement for a minimum of 6 months. In the future, we hope to define a precise curriculum for assessments. Technological advances may provide solutions-improvements in telemedicine may have neonatologists assessing haemodynamic status with paediatric cardiologists excluding structural lesions and neonatal echocardiography simulators could increase exposure to multiple pathologies and allow limitless practice in image acquisition. CONCLUSION: We propose developing training places in specialist paediatric cardiology centres and neonatal units to facilitate training and suggest all UK practitioners performing neonatologist performed echocardiogram adopt this current best practice statement. WHAT IS KNOWN: Neonatologist-performed echocardiogram (NoPE) also known as targeted neonatal echocardiography (TNE) or functional ECHO is increasingly recognised and utilised in care of sick newborn and premature babies. There are differences in training for echocardiography across continents and formal accreditation processes are lacking. WHAT IS NEW: This is the first document of consensus best practice statement for training of neonatologists in neonatologist-performed echocardiogram (NoPE), jointly drafted by Neonatologists with interest in cardiology & haemodynamics (NICHe), paediatric cardiology and paediatricians with expertise in cardiology interest groups in UK. Key elements of a code of practice for neonatologist-performed echocardiogram are suggested. PMID- 26362540 TI - Comparison of scleral buckling and vitrectomy using wide angle viewing system for rhegmatogenous retinal detachment in patients older than 35 years. AB - BACKGROUND: To compare scleral buckling (SB) and pars plana vitrectomy (PPV) using a wide angle viewing system (WAVS) for uncomplicated phakic rhegmatogenous retinal detachment (RRD). METHODS: The medical records of patients with uncomplicated phakic RRD were retrospectively reviewed. Eyes with pseudophakic or attached fovea were excluded. Patients treated with SB were classified as group B, and PPV using WAVS as group V. Primary success rate, visual acuity (VA), macular complications, and sustained subretinal fluid (SRF) were compared between groups. RESULTS: Seventy-two eyes were included in group B and 57 eyes in group V. Group B had better preoperative VA (1.38 +/- 0.87 vs 1.84 +/- 0.97 in LogMAR, P = 0.010), but worse final VA (0.51 +/- 0.48 vs 0.30 +/- 0.23, P = 0.012) than group V. The primary success rate of 94.7 % in group V was higher than 77.8 % in group B (P = 0.010). Final success rate was 100 % in both groups. There was no significant difference in macular complications between groups (P = 0.087). Sustained SRF was found in 22 eyes in group B (38.6 %), while only two eyes in group V exhibited sustained SRF (2.8 %, P < 0.001). CONCLUSIONS: Pars plana vitrectomy using WAVS was more efficacious than SB for treating uncomplicated phakic RRD. PMID- 26362542 TI - Class-specific regulation of pro-inflammatory genes by MyD88 pathways and IkappaBzeta. PMID- 26362543 TI - WD repeat-containing protein 5 (WDR5) localizes to the midbody and regulates abscission. PMID- 26362541 TI - Comparing the effectiveness of selective laser trabeculoplasty with topical medication as initial treatment (the Glaucoma Initial Treatment Study): study protocol for a randomised controlled trial. AB - BACKGROUND: Glaucoma is the leading cause of irreversible blindness in the world. Estimated to affect 60 million people worldwide, this figure is expected to rise to 80 million by 2020. Untreated, glaucoma leads to visual decay and eventually to blindness, and can significantly reduce quality of life. First-line treatment in patients with primary open-angle glaucoma and exfoliative glaucoma is topical medical therapy with ocular hypotensives as eye drops. However, eye drops have several disadvantages including cost, possible local and systemic side effects, and adherence and perseverance issues. Randomised controlled trials have demonstrated that selective laser trabeculoplasty is equally as effective in lowering intraocular pressure as eye drops. However, the impact of these two treatment modalities from the patient and economic perspectives has not been adequately determined. Thus, it remains unclear whether topical medical therapy or selective laser trabeculoplasty should be recommended as first-line treatment for glaucoma. METHODS/DESIGN: This protocol describes an international, multi centre, randomised controlled trial to determine the optimum first-line therapy for people with primary open-angle glaucoma and exfoliative glaucoma. This study will compare the effect of selective laser trabeculoplasty and topical medication with respect to patients' generic and glaucoma-specific quality of life. The trial will also provide a detailed cost-effectiveness analysis and compare the clinical effectiveness with respect to the degree of intraocular pressure lowering and rates of treatment failure. Research coordinators in each centre will identify and recruit previously untreated patients with primary open-angle glaucoma and exfoliative glaucoma. Those who meet the eligibility criteria will be invited to enter a randomised controlled trial with either selective laser trabeculoplasty or topical ocular hypotensive therapy, according to a stepped regimen. Outcome assessment will be measured at 6 weeks and at 6, 12, and 24 months post-treatment. Regular clinic follow-ups will continue as clinically indicated between study outcome visits. DISCUSSION: The Glaucoma Initial Treatment Study is the first multi-centred RCT to determine the optimum first line therapy for people with glaucoma. Our trial will have an unprecedented capacity to meaningfully transform the treatment and management of glaucoma in Australia and overseas. TRIAL REGISTRATION: ACTRN12611000720910; Date registered: 11 July 2011. PMID- 26362544 TI - Validity and practical utility of accelerometry for the measurement of in-hand physical activity in horses. AB - BACKGROUND: Accelerometers are valid, practical and reliable tools for the measurement of habitual physical activity (PA). Quantification of PA in horses is desirable for use in research and clinical settings. The objective of this study was to evaluate a triaxial accelerometer for objective measurement of PA in the horse by assessment of their practical utility and validity. Horses were recruited to establish both the optimal site of accelerometer attachment and questionnaire designed to explore owner acceptance. Validity and cut-off values were obtained by assessing PA at various gaits. Validation study- 20 horses wore the accelerometer while being filmed for 10 min each of rest, walking and trotting and 5 mins of canter work. Practical utility study- five horses wore accelerometers on polls and withers for 18 h; compliance and relative data losses were quantified. RESULTS: Accelerometry output differed significantly between the four PA levels (P < 0*001) for both wither and poll placement. For withers placement, ROC analyses found optimal sensitivity and specificity at a cut-off of <47 counts per minute (cpm) for rest (sensitivity 99.5 %, specificity 100 %), 967 2424 cpm for trotting (sensitivity 96.7 %, specificity 100 %) and >=2425 cpm for cantering (sensitivity 96.0 %, specificity 97.0 %). Attachment at the poll resulted in optimal sensitivity and specificity at a cut-off of <707 counts per minute (cpm) for rest (sensitivity 97.5 %, specificity 99.6 %), 1546-2609 cpm for trotting (sensitivity 90.33 %, specificity 79.25 %) and >=2610 cpm for cantering (sensitivity 100 %, specificity 100 %) In terms of practical utility, accelerometry was well tolerated and owner acceptance high. CONCLUSION: Accelerometry data correlated well with varying levels of in-hand equine activity. The use of accelerometers is a valid method for objective measurement of controlled PA in the horse. PMID- 26362545 TI - Anterior chest wall resection and reconstruction for locally advanced breast cancer. AB - With breast cancer awareness, the incidence of large invasive tumours is rare. We present a video of locally advanced breast cancer invading the anterior chest wall requiring en bloc resection that resulted in a large chest wall defect with exposed pleural and pericardial surface. Skeletal reconstruction and provision of adequate soft tissue coverage in order to avoid respiratory failure was challenging. A 58-year-old female presented with a 3-year history of locally invasive breast carcinoma with contiguous spread to sternum, clavicles, sternoclavicular joints and bilateral second to fifth ribs. She underwent total sternectomy, bilateral second to fifth ribs and chest wall resection resulting in a 21 * 18 cm chest wall defect. Reconstruction of her sternum was with methyl methacrylate cement prosthesis. Ribs were reconstructed with titanium plates. Soft tissue coverage was achieved with left vertical rectus abdominis pedicle flap, right external oblique transposition flap and a right latissimus dorsi free flap. Flap failure necessitated a right vastus lateralis free flap. She was discharged ambulant without respiratory compromise. Resection and reconstruction of large chest wall defects is possible due to new bioprosthetic materials and is possible with acceptable morbidity and mortality. PMID- 26362546 TI - Effects of Spectral Degradation on Attentional Modulation of Cortical Auditory Responses to Continuous Speech. AB - This study investigates the effect of spectral degradation on cortical speech encoding in complex auditory scenes. Young normal-hearing listeners were simultaneously presented with two speech streams and were instructed to attend to only one of them. The speech mixtures were subjected to noise-channel vocoding to preserve the temporal envelope and degrade the spectral information of speech. Each subject was tested with five spectral resolution conditions (unprocessed speech, 64-, 32-, 16-, and 8-channel vocoder conditions) and two target-to-masker ratio (TMR) conditions (3 and 0 dB). Ongoing electroencephalographic (EEG) responses and speech comprehension were measured in each spectral and TMR condition for each subject. Neural tracking of each speech stream was characterized by cross-correlating the EEG responses with the envelope of each of the simultaneous speech streams at different time lags. Results showed that spectral degradation and TMR both significantly influenced how top-down attention modulated the EEG responses to the attended and unattended speech. That is, the EEG responses to the attended and unattended speech streams differed more for the higher (unprocessed, 64 ch, and 32 ch) than the lower (16 and 8 ch) spectral resolution conditions, as well as for the higher (3 dB) than the lower TMR (0 dB) condition. The magnitude of differential neural modulation responses to the attended and unattended speech streams significantly correlated with speech comprehension scores. These results suggest that severe spectral degradation and low TMR hinder speech stream segregation, making it difficult to employ top-down attention to differentially process different speech streams. PMID- 26362547 TI - Implications of the "Consensus Communication on Early Peanut Introduction in the Prevention of Peanut Allergy in High-Risk Infants" for Allergists, Primary Care Physicians, Patients, and Society. PMID- 26362548 TI - Contact Dermatitis for the Practicing Allergist. AB - This article provides an overview of important practice recommendations from the recently updated Contact Dermatitis Practice Parameter. This updated parameter provides essential recommendations pertaining to clinical history, physical examination, and patch testing evaluation of patients suspected of allergic contact dermatitis. In addition to providing guidance for performing and interpreting closed patch testing, the updated parameter provides concrete recommendations for assessing metal hypersensitivity in patients receiving prosthetic devices, for evaluating workers with occupational contact dermatitis, and also for addressing allergic contact dermatitis in children. Finally, the document provides practical recommendations useful for educating patients regarding avoidance of exposure to known contact sensitizers in the home and at work. The Contact Dermatitis Parameter is designed as a practical, evidence-based clinical tool to be used by allergists and dermatologists who routinely are called upon to evaluate patients with skin disorders. PMID- 26362549 TI - Pediatric Allergic Contact Dermatitis: Lessons for Better Care. AB - Allergic contact dermatitis (ACD) is an immune-mediated condition that is likely underrecognized in children. ACD is the result of primary sensitization and secondary elicitation by allergy-provoking haptens. A detailed clinical history and physical examination may yield diagnosis. Patch testing is the criterion standard diagnostic tool for confirming the diagnosis of ACD in both children and adults. Herein, we present an overview of pediatric ACD, an analysis of relevant current literature on the topic, focused management recommendations, and a discussion of existing knowledge gaps that must be addressed by future research. PMID- 26362550 TI - Allergy to Surgical Implants. AB - Surgical implants have a wide array of therapeutic uses, most commonly in joint replacements, but also in repair of pes excavatum and spinal disorders, in cardiac devices (stents, patches, pacers, valves), in gynecological implants, and in dentistry. Many of the metals used are immunologically active, as are the methacrylates and epoxies used in conjunction with several of these devices. Allergic responses to surgical components can present atypically as failure of the device, with nonspecific symptoms of localized pain, swelling, warmth, loosening, instability, itching, or burning; localized rash is infrequent. Identification of the specific metal and cement components used in a particular implant can be difficult, but is crucial to guide testing and interpretation of results. Nickel, cobalt, and chromium remain the most common metals implicated in implant failure due to metal sensitization; methacrylate-based cements are also important contributors. This review will provide a guide on how to assess and interpret the clinical history, identify the components used in surgery, test for sensitization, and provide advice on possible solutions. Data on the pathways of metal-induced immune stimulation are included. In this setting, the allergist, the dermatologist, or both have the potential to significantly improve surgical outcomes and patient care. PMID- 26362551 TI - Over-the-Counter Oral Phenylephrine: A Placebo for Nasal Congestion. PMID- 26362552 TI - How Patient Experiences Should Change Our Approach to Treating Patients with Aspirin-Exacerbated Respiratory Disease. PMID- 26362553 TI - Ultrafine-Particle Inhalers, the Holy Grail of Inhaled Corticosteroid Therapy, or Not! PMID- 26362554 TI - Chronic Rhinosinusitis. PMID- 26362555 TI - Epinephrine autoinjectors: Compression and propulsion do have a role in delivery depth. PMID- 26362556 TI - Reply: To PMID 25634219. PMID- 26362557 TI - A useful method to detect opioid allergies. PMID- 26362558 TI - Reply: To PMID 25956313. PMID- 26362559 TI - Understanding long-term opioid prescribing for non-cancer pain in primary care: a qualitative study. AB - BACKGROUND: The place of opioids in the management of chronic, non-cancer pain is limited. Even so their use is escalating, leading to concerns that patients are prescribed strong opioids inappropriately and alternatives to medication are under-used. We aimed to understand the processes which bring about and perpetuate long-term prescribing of opioids for chronic, non-cancer pain. METHODS: We held semi-structured interviews with patients and focus groups with general practitioners (GPs). Participants included 23 patients currently prescribed long term opioids and 15 GPs from Leeds and Bradford, United Kingdom (UK). We used a grounded approach to the analysis of transcripts. RESULTS: Patients are driven by the needs for pain relief, explanation, and improvement or maintenance of quality of life. GPs' responses are shaped by how UK general practice is organised, available therapeutic choices and their expertise in managing chronic pain, especially when facing diagnostic uncertainty or when their own approach is at odds with the patient's wishes. Four features of the resulting transaction between patients and doctors influence prescribing: lack of clarity of strategy, including the risk of any plans being subverted by urgent demands; lack of certainty about locus of control in decision-making, especially in relation to prescribing; continuity in the doctor-patient relationship; and mutuality and trust. CONCLUSIONS: Problematic prescribing occurs when patients experience repeated consultations that do not meet their needs and GPs feel unable to negotiate alternative approaches to treatment. Therapeutic short-termism is perpetuated by inconsistent clinical encounters and the absence of mutually agreed formulations of underlying problems and plans of action. Apart from commissioning improved access to appropriate specialist services, general practices should also consider how they manage problematic opioid prescribing and be prepared to set boundaries with patients. PMID- 26362560 TI - Promoting conversations between physicians and families about childhood obesity: evaluation of physician communication training within a clinical practice improvement initiative. AB - Childhood obesity rates have incrementally increased since the 1980s, sparking calls for initiatives focused on addressing this public health concern. In response, the family medicine residency clinic profiled in this research designed, executed, and evaluated a practice improvement initiative focused on physician communication behaviors and clinic processes that impact the management of unhealthy pediatric weight. The results of the evaluation effort demonstrated increased physician knowledge of communication principles, improvements in weight management counseling rates, and opportunities for health delivery system changes to promote the effective clinical management of unhealthy pediatric weight. PMID- 26362561 TI - Effects of Running on Chronic Diseases and Cardiovascular and All-Cause Mortality. AB - Considerable evidence has established the link between high levels of physical activity (PA) and all-cause and cardiovascular disease (CVD)-specific mortality. Running is a popular form of vigorous PA that has been associated with better overall survival, but there is debate about the dose-response relationship between running and CVD and all-cause survival. In this review, we specifically reviewed studies published in PubMed since 2000 that included at least 500 runners and 5-year follow-up so as to analyze the relationship between vigorous aerobic PA, specifically running, and major health consequences, especially CVD and all-cause mortality. We also made recommendations on the optimal dose of running associated with protection against CVD and premature mortality, as well as briefly discuss the potential cardiotoxicity of a high dose of aerobic exercise, including running (eg, marathons). PMID- 26362562 TI - Technology support to a telehealth in the home service: Qualitative observations. AB - INTRODUCTION: The Flinders University Telehealth in the Home (FTH) trial was an action research initiative that introduced and evaluated the impact of telehealth services on palliative care patients living in the community, home-based rehabilitation services for the elderly, and services to the elderly in residential aged care. The aim of this study was to understand the issues encountered during the provision of technology services that supported this trial. METHODS: A mixed methods approach was undertaken to analyse the roles of information and communication technology (ICT) and clinical staff in design, technology management and training. The data sources were staff observations and documents including job logs, meetings, emails and technology descriptions. RESULTS: Use of consumer technology for telehealth required customisation of applications and services. Clinicians played a key role in definition of applications and the embedding of workflow into applications. Usability of applications was key to their subsequent use. Management of design creep and technology services, coupled with support and training for clinicians were important to maintenance of a telehealth service. DISCUSSION: In the setting described, an iterative approach to the development of telehealth services to the home using consumer technologies was needed. The efficient management of consumer devices in multiple settings will become critical as telehealth services grow in scale. Effective collaboration between clinical and technical stakeholders and further workforce education in telehealth can be key enablers for the transition of face-to-face care to a telehealth mode of delivery. PMID- 26362563 TI - Feasibility of telemedicine or telephone-based family intervention for rural paediatric obesity: Cluster randomized control trial. PMID- 26362564 TI - Effects of dextromethorphan as add-on to sitagliptin on blood glucose and serum insulin concentrations in individuals with type 2 diabetes mellitus: a randomized, placebo-controlled, double-blinded, multiple crossover, single-dose clinical trial. AB - In this clinical trial, we investigated the blood glucose (BG)-lowering effects of 30, 60 and 90 mg dextromethorphan (DXM) as well as 100 mg sitagliptin alone versus combinations of DXM and sitagliptin during an oral glucose tolerance test (OGTT) in 20 men with T2DM. The combination of 60 mg DXM plus 100 mg sitagliptin was observed to have the strongest effect in the OGTT. It lowered maximum BG concentrations and increased the baseline-adjusted area under the curve for serum insulin concentrations in the first 30 min of the OGTT (mean +/- standard deviation 240 +/- 47 mg/dl and 8.1 +/- 6.1 mU/l/h, respectively) to a significantly larger extent than did 100 mg sitagliptin alone (254 +/- 50 mg/dl and 5.8 +/- 2.5 mU/l/h, respectively; p < 0.05) and placebo (272 +/- 49 mg/dl and 3.9 +/- 3.0 mU/l/h, respectively; p < 0.001). All study drugs were well tolerated, alone and in combination, without serious adverse events or hypoglycaemia. Long-term clinical trials are now warranted to investigate the potential of the combination of 30 or 60 mg DXM and dipeptidyl peptidase-4 inhibitors in the treatment of individuals with T2DM, in particular as preclinical studies have identified the beta-cell protective properties of DXM. PMID- 26362565 TI - Novel Iminocoumarin Derivatives: Synthesis, Spectroscopic and Computational Studies. AB - Three novel iminocoumarin derivatives with high quantum yield are synthesized from 3-benzimidazole substituted coumarin and different aromatic aldehydes. The photophysical behavior of the synthesized compounds was studied using UV-visible and fluorescence spectroscopy in polar and non-polar solvents. The compounds show absorption maxima at around 450 nm and emission maxima at around 500 nm. The quantum yields of compounds in dichloromethane and chloroform are more than 0.90. The absorption, emission and quantum yield of compounds are dependent on the polarity of solvents. Along with an intense absorption, these compounds show shoulder absorption peak in the studied solvents. The solvent polarity plots revealed the charge transfer process in the synthesized molecules from donor to acceptor. Density Functional Theory and Time Dependent Density Functional Theory computations have been used to have more understanding of the structural, molecular, electronic and photophysical parameters of the dyes. The dyes were characterized by FT-IR, (1)H NMR, (13)C NMR and mass spectral analysis. PMID- 26362566 TI - Corticosteroids for acute bacterial meningitis. AB - BACKGROUND: In experimental studies, the outcome of bacterial meningitis has been related to the severity of inflammation in the subarachnoid space. Corticosteroids reduce this inflammatory response. OBJECTIVES: To examine the effect of adjuvant corticosteroid therapy versus placebo on mortality, hearing loss and neurological sequelae in people of all ages with acute bacterial meningitis. SEARCH METHODS: We searched CENTRAL (2015, Issue 1), MEDLINE (1966 to January week 4, 2015), EMBASE (1974 to February 2015), Web of Science (2010 to February 2015), CINAHL (2010 to February 2015) and LILACS (2010 to February 2015). SELECTION CRITERIA: Randomised controlled trials (RCTs) of corticosteroids for acute bacterial meningitis. DATA COLLECTION AND ANALYSIS: We scored RCTs for methodological quality. We collected outcomes and adverse effects. We performed subgroup analyses for children and adults, causative organisms, low-income versus high-income countries, time of steroid administration and study quality. MAIN RESULTS: We included 25 studies involving 4121 participants (2511 children and 1517 adults; 93 mixed population). Four studies were of high quality with no risk of bias, 14 of medium quality and seven of low quality, indicating a moderate risk of bias for the total analysis. Nine studies were performed in low-income countries and 16 in high-income countries.Corticosteroids were associated with a non-significant reduction in mortality (17.8% versus 19.9%; risk ratio (RR) 0.90, 95% confidence interval (CI) 0.80 to 1.01, P value = 0.07). A similar non significant reduction in mortality was observed in adults receiving corticosteroids (RR 0.74, 95% CI 0.53 to 1.05, P value = 0.09). Corticosteroids were associated with lower rates of severe hearing loss (RR 0.67, 95% CI 0.51 to 0.88), any hearing loss (RR 0.74, 95% CI 0.63 to 0.87) and neurological sequelae (RR 0.83, 95% CI 0.69 to 1.00).Subgroup analyses for causative organisms showed that corticosteroids reduced mortality in Streptococcus pneumoniae (S. pneumoniae) meningitis (RR 0.84, 95% CI 0.72 to 0.98), but not in Haemophilus influenzae (H. influenzae) orNeisseria meningitidis (N. meningitidis) meningitis. Corticosteroids reduced severe hearing loss in children with H. influenzae meningitis (RR 0.34, 95% CI 0.20 to 0.59) but not in children with meningitis due to non-Haemophilus species.In high-income countries, corticosteroids reduced severe hearing loss (RR 0.51, 95% CI 0.35 to 0.73), any hearing loss (RR 0.58, 95% CI 0.45 to 0.73) and short-term neurological sequelae (RR 0.64, 95% CI 0.48 to 0.85). There was no beneficial effect of corticosteroid therapy in low-income countries.Subgroup analysis for study quality showed no effect of corticosteroids on severe hearing loss in high-quality studies.Corticosteroid treatment was associated with an increase in recurrent fever (RR 1.27, 95% CI 1.09 to 1.47), but not with other adverse events. AUTHORS' CONCLUSIONS: Corticosteroids significantly reduced hearing loss and neurological sequelae, but did not reduce overall mortality. Data support the use of corticosteroids in patients with bacterial meningitis in high-income countries. We found no beneficial effect in low-income countries. PMID- 26362567 TI - Life expectancy of young adults with follicular lymphoma. AB - BACKGROUND: This study was aimed at investigating the clinical features and outcomes of follicular lymphoma (FL) patients younger than 40 years, which have not been extensively investigated yet. PATIENTS AND METHODS: One hundred and fifty-five patients younger than 40 years were retrospectively studied from a series of 1002 FL patients diagnosed in four different European Oncology Centres (Barcelona, Spain; Bellinzona, Switzerland; London, UK; Novara, Italy) from 1985 to 2010. RESULTS: Patients younger than 40 had a lower incidence of elevated LDH, high beta2-microglobulin, and a high-risk Follicular Lymphoma International Prognostic Index (FLIPI) score, whereas bone marrow involvement and bulky and disseminated lymphadenopathy were more frequent. At a median follow-up of 10 years, younger patients, in comparison with those older than 40, had significantly better overall (OS), cause-specific survival (CSS), and progression free survival (PFS), with 10-year OS rate of 81% versus 51% (P < 0.0001), 10-year CSS rate of 82% versus 60% (P < 0.0001), and 10-year PFS of 39% versus 24% (P = 0.0098). However, there were no significant CSS and PFS differences in comparison with the patients aged 40-60. In multivariate analysis, having the lymphoma diagnosed in the last two decades and a favourable FLIPI score were associated with a significantly longer PFS and CSS in younger patients, whereas only FLIPI retained statistical significance for OS. CONCLUSIONS: In our series, FL patients younger than 40 have a median OS of 24 years and their outcome seems to be improving over time. However, they still have a significantly shorter life expectancy than that of an age-matched general healthy population. PMID- 26362568 TI - Disease characteristics, treatment patterns, and outcomes of follicular lymphoma in patients 40 years of age and younger: an analysis from the National Lymphocare Study?. AB - BACKGROUND: Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma, with median age at diagnosis in the seventh decade. FL in young adults (YAs), defined as diagnosis at <=40 years, is uncommon. No standard approaches exist guiding the treatment of YA FL, and little is known about their disease characteristics and outcomes. To gain further insights into YA FL, we analyzed the National LymphoCare Study (NLCS) to describe characteristics, initial treatments, and outcomes in this population versus patients aged >40 years. PATIENTS AND METHODS: Using the NLCS database, we stratified FL patients by age: 18-40 (YA), 41-60, 61-70, 71-80, and >80 years. Survival probability was estimated using Kaplan-Meier methodology. We examined associations between age and survival using hazard ratios and 95% confidence intervals (CIs) from multivariable Cox models. RESULTS: Of 2652 eligible FL patients in the NLCS, 164 (6%) were YAs. Of YA patients, 69% had advanced disease, 80% had low-grade histology, and 50% had good-risk disease according to the Follicular Lymphoma International Prognostic Index (FLIPI). Nineteen percent underwent observation, 12% received rituximab monotherapy, and 46% received chemoimmunotherapy [in 59% of these: R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone)]. With a median follow-up of 8 years, overall survival (OS) at 2, 5, and 8 years was 98% (95% CI 93-99), 94% (95% CI 89-97), and 90% (95% CI 83-94), respectively. Median progression-free survival (PFS) was 7.3 years (95% CI 5.6 not reached). CONCLUSIONS: In one of the largest cohorts of YA FL patients treated in the rituximab era, disease characteristics and outcomes were similar to patients aged 41-60 years, with favorable OS and PFS in YAs. Longer-term outcomes and YA-specific survivorship concerns should be considered when defining management. These data may not support the need for more aggressive therapies in YA FL. CLINICAL TRIAL NUMBER: Roche/Genentech ML01377 (U2963n). PMID- 26362569 TI - Potential of the microbial assay for risk assessment (MARA) for assessing ecotoxicological effects of herbicides to non-target organisms. AB - Many microbiotests that have been proposed for use in the risk assessment of environmental pollutants have the drawback of lacking relevant published data on various aspects of their test application possibilities and therefore do not receive the regulatory recognition which they may deserve. The MARA bioassay lacks published data for many relevant environmental pollutants, particularly pesticides and this may limit its use in regulatory framework. The present study has assessed the sensitivity of the MARA bioassay relative to other established bioassays (Daphnia magna and Oreochromis niloticus) to two widely used herbicide formulations: Roundup (having glyphosate as active ingredient) and Herbextra (with the active ingredient being 2,4-dichlorophenoxyacetic acid-2,4-D). Roundup was found to be more toxic than Herbextra in all three bioassays. The D. magna EC50 s obtained for Roundup and Herbextra were respectively 5.55 and 356.61 mg/l while the LC50 s for O. niloticus were 11.30 and 222,28 mg/l respectively. In the case of the MARA bioassay microbial toxic concentrations (MTCs) for individual species ranged from 6.85 to 468 mg/l with an overall mean MTC of 101.82 mg/l for glyphosate and from 74.67 to 13,333 mg/l for 2,4-D giving an overall mean MTC of 2855.88 mg/l. Although the overall MTCs from the MARA bioassay were much higher than the LC50 s and EC50 s from the fish and daphnia bioassays respectively, the most sensitive MARA organism for each of the herbicides had MTCs that were comparable to or lower than the corresponding endpoints from the other bioassays implying that the MARA assay is a potentially useful bioassay for risk assessment of pesticides. PMID- 26362570 TI - [Salmon-pink colored conjunctival tumor with amyloid deposits]. AB - An 82-year-old male patient presented with a salmon-pink colored conjunctival tumor of the left eye. A circumscribed, dense and whitish portion was detected by clinical examination. The histophological and immunhistochemical examination of the biopsy tissue revealed a CD20+ marginal zone lymphoma of the conjunctiva with amyloid deposits. Extranodal marginal zone lymphoma at this site is the most common lymphoma of the ocular adnexa and accounts for 5-10% of malignant diseases. An association with amyloid production is very rare and according to the current state of knowledge has no known impact on the outcome. PMID- 26362571 TI - The Collection and Analysis of Carbon Monoxide Levels as an Indirect Measure of Smoke Exposure in Pregnant Adolescents at a Multidisciplinary Teen Obstetrics Clinic. AB - STUDY OBJECTIVE: In this study we aimed to collect and analyze CO levels as an indirect measure of smoke exposure in pregnant adolescents. DESIGN, SETTING, AND PARTICIPANTS: Participants included pregnant adolescents who received antenatal care over 18 months (2012-2013) at the Multidisciplinary Teen Obstetrics Clinic at a tertiary-care hospital in Southeastern Ontario. INTERVENTIONS: The CO breath test is a noninvasive method that is used to assess smoke exposure, in which nonsmokers have levels of 0-6 ppm, and levels of 7-10, 11-20 and more than 20 ppm are consistent with light, typical, and heavy smokers, respectively. Expired CO, smoking status, cigarette number, and home secondhand smoke exposure were documented at 3 clinic visits. MAIN OUTCOME MEASURES: To determine mean CO levels as a measure of smoke exposure and prevalence of secondhand smoke exposure. RESULTS: The mean age of participants was 17.6 years. CO means (ppm) across 3 visits were 6.0, 5.9, and 4.8. Sixty-two percent of patients were self-reported nonsmokers, 38% were self-reported smokers (n = 93). CO means (standard error of the mean) were consistently different for nonsmokers vs smokers at visits 1 to 3, respectively: 2.9 (0.79) vs 9.7 (1.8); 3.0 (0.71) vs 12.9 (2.2), and 2.4 (0.71) vs 8.8 (1.5; P < .01, t test; n = 91). Of patient's highest CO (COmax), 62%, 9%, 15%, and 12% had levels of 6 or less, 7-10, 11-20, and greater than 20, respectively. Eighty-four percent of pregnant adolescents had home secondhand smoke exposure, which included 40% of nonsmokers and 100% of smokers (n = 57). Although most nonsmokers had a COmax of 6 or fewer ppm, 56% of smokers had COmax greater than 10 ppm (P < .05, chi(2)). CONCLUSION: Emphasis on smoking cessation is imperative in pregnant adolescents and should particularly target partners and families, because secondhand smoke exposure was very prevalent. PMID- 26362572 TI - Cross-Family Comparative Proteomic Study and Molecular Phylogeny of MAP Kinases in Plants. AB - Mitogen-activated protein kinases are serine/threonine-specific protein kinases and they are closely related to cyclin-dependent kinases. They constitute functionally significant family of proteins that is involved in various cellular functions like response to mitogens, osmotic stress, heat shock and proinflammatory cytokines as well as known to play key role in proliferation, gene expression, differentiation, mitosis, cell survival, and apoptosis. MAP kinases are characteristically found in eukaryotes only, though they are fairly diverse and encountered in all animals, fungi and plants, and even in an array of unicellular eukaryotes. In this study 24 MAP kinase sequences from various plant species were selected in order to compare their conserved regions, amino acid composition, evolutionary orders and other statistical parameters. PMID- 26362573 TI - Expression patterns and quantitative assessment of neurochemical markers in the lung of the gray bichir, Polypterus senegalus (Cuvier, 1829). AB - Anatomical and functional studies of the autonomic innervation and the putative oxygen receptors-the neuroepithelial (NEC)-like cells of the bichirs are lacking. The present paper describes the distribution of both NEC-like cells and the polymorphous granular cells (PGCs) that populate the mucociliated epithelium of the lung in the air breathing fish Polypterus senegalus. By using confocal immunohistochemistry we determined the coexpression of specific neurochemical markers. Colocalization studies showed that 5HT is coexpressed with calbindin and nNOS in the NEC-like cells and PGCs, and choline acetyltransferase (ChAT) is coexpressed with nNOS in both the two types of cells. Distribution of neurotransmitters (5HT, NO) and neurochemical marker ChAT is also investigated in the lung muscle. The role of these transmitters may be the autonomic control of circulation and respiration. However, the importance of these signals for the respiratory responses in the species studied is still not known. The present study also shows for the first time the simultaneous occurrence of piscidin 1 and 5HT in the PGCs. The function of these cells being equivalent to ones found in fish gill subepithelial parenchyma, is still not known. Due to the importance of piscidin 1 in local immune defense, more research is useful to understand a possible interaction of PGCs with immune response in the bichir lung. PMID- 26362574 TI - Implementation of Computerized Physician Order Entry Is Associated With Increased Thrombolytic Administration for Emergency Department Patients With Acute Ischemic Stroke. AB - STUDY OBJECTIVE: Electronic health record systems with computerized physician order entry and condition-specific order sets are intended to standardize patient management and minimize errors of omission. However, the effect of these systems on disease-specific process measures and patient outcomes is not well established. We seek to evaluate the effect of computerized physician order entry electronic health record implementation on process measures and short-term health outcomes for patients hospitalized with acute ischemic stroke. METHODS: We conducted a quasi-experimental cohort study of patients hospitalized for acute ischemic stroke with concurrent controls that took advantage of the staggered implementation of a comprehensive computerized physician order entry electronic health record across 16 medical centers within an integrated health care delivery system from 2007 to 2012. The study population included all patients admitted to the hospital from the emergency department (ED) for acute ischemic stroke, with an initial neuroimaging study within 2.5 hours of ED arrival. We evaluated the association between the availability of a computerized physician order entry electronic health record and the rates of ED intravenous tissue plasminogen activator administration, hospital-acquired pneumonia, and inhospital and 90-day mortality, using doubly robust estimation models to adjust for demographics, comorbidities, secular trends, and concurrent primary stroke center certification status at each center. RESULTS: Of 10,081 eligible patients, 6,686 (66.3%) were treated in centers after the computerized physician order entry electronic health record had been implemented. Computerized physician order entry was associated with significantly higher rates of intravenous tissue plasminogen activator administration (rate difference 3.4%; 95% confidence interval 0.8% to 6.0%) but not with significant rate differences in pneumonia or mortality. CONCLUSION: For patients hospitalized for acute ischemic stroke, computerized physician order entry use was associated with increased use of intravenous tissue plasminogen activator. PMID- 26362576 TI - QRS-based assessment of myocardial damage and adverse events associated with cardiac sarcoidosis. AB - BACKGROUND: Cardiac sarcoidosis (CS) generates myocardial scar and arrhythmogenic substrate. CS diagnosis according to the Japanese Ministry of Health and Welfare guidelines relies, among others, on cardiac magnetic resonance imaging with late gadolinium enhancement (CMR-LGE). However, access to CMR-LGE is limited. The electrocardiography-based Selvester QRS score has been validated for identifying myocardial scar in ischemic/nonischemic cardiomyopathy, but its efficacy has not been tested to evaluate CS. OBJECTIVE: The purpose of this study was to examine whether the QRS score can be applied to CS. METHODS: CS-associated myocardial scar was assessed by both CMR-LGE and QRS scoring in patients with extra-CS (n = 59). RESULTS: Of 59 patients, 35 (59%) were diagnosed with CS according to the Japanese Ministry of Health and Welfare guidelines. QRS-estimated scar mass positively correlated with that quantified by CMR-LGE (signal intensity >=2SD above the reference; r = 0.68; P < .001). Receiver operating characteristic curves demonstrated optimal cutoffs of 9% CMR-LGE scar and 3-point QRS score to identify patients with CS. The areas under the curves of CMR-LGE and the QRS score were not significantly different (0.83 and 0.78, respectively; P = .27); both methods demonstrated similar diagnostic performance. A QRS score of >=3 led to a higher incidence of CS-associated adverse events (death/fatal arrhythmia/heart failure hospitalization) than did a QRS score of <3 (35 +/- 21 months of follow-up; P = .01). QRS score was an independent predictor of risk in multivariate analysis (P = .03). CONCLUSION: The Selvester QRS scoring estimates CS-associated myocardial damage and identifies patients with CS equally well as CMR-LGE. A higher QRS score is also associated with an increased risk of life threatening events in CS, indicating its potential use as a risk predictor. PMID- 26362577 TI - Prevalence of subcutaneous implantable cardioverter-defibrillator candidacy based on template ECG screening in patients with hypertrophic cardiomyopathy. AB - BACKGROUND: Subcutaneous implantable cardioverter-defibrillator (S-ICD) is a promising option for patients with hypertrophic cardiomyopathy (HCM). Patients with HCM can present markedly abnormal electrocardiograms (ECGs), and there are no data on what percentage of patients with HCM fail the prerequisite S-ICD vector screening. OBJECTIVE: The purpose of this study was to determine the failure rate of the prerequisite vector screening using 1 or 2 acceptable vectors stratified for risk profile for sudden cardiac death and predictors of failure. METHODS: ECG recordings from consecutive patients with HCM simulating the S-ICD sensing vectors were analyzed with the S-ICD screening tool. Eligibility was defined by 1 or 2 appropriate vectors. Medical history, ultrasound characteristics, and 12-lead ECG characteristics were analyzed and the individual arrhythmic risk at 5 year was determined to study potential predictors of failure. RESULTS: One hundred sixty-five (118 men; mean age 51 +/- 16 years) patients were analyzed. Twenty-two patients (13%) had a high risk of sudden cardiac death, 33 (20%) had intermediate to high risk, and 110 (67%) had low risk. Twenty-six patients (16%) had no suitable vector, including 8 of 22 high risk patients (36%). The primary cause of failure was high T-wave voltages in 25% of the vectors analyzed. T-wave inversions in >2 leads on the surface 12-lead ECG (odds ratio 15.6; 95% confidence interval 4.9-50.3; P < .001) and prior myectomy (odds ratio 8.4; 95% confidence interval 2.1-33.1; P = .002) were significantly associated with screening failure in a multivariable model. CONCLUSION: Currently available preimplant screening algorithms recommended by the manufacturer are associated with a significant failure rate in patients with HCM, particularly in the high-risk subgroup. PMID- 26362578 TI - Changes in triglyceride levels in ultra-high risk for psychosis individuals treated with omega-3 fatty acids. AB - AIM: The aim of this analysis was to assess changes in lipid parameters, specifically in triglyceride (TG) levels, in a population at ultra-high risk (UHR) for psychosis treated with omega-3 polyunsaturated fatty acids (PUFAs) versus placebo. METHODS: Data were derived from a randomized, double-blind, placebo-controlled trial conducted at an early psychosis unit. Eighty-one individuals, aged 13-25 years, at UHR for psychosis participated in a 12-week intervention trial of 1.2 g/day of omega-3 PUFAs (n = 41) versus placebo (n = 40). Lipid and C-reactive protein levels were collected at baseline and after 12 weeks. RESULTS: Between-group comparisons showed no significant difference in TG levels after the intervention. However, in individuals with baseline TG levels above 150 mg dL-1 there was a significant mean TG reduction of 67.29 (SD 42.54; P = 0.006) in the omega-3 group (n = 7). CONCLUSION: In this sample of UHR individuals, a 12-week intervention with omega-3 PUFAs was effective in reducing previously elevated TG levels. This might introduce the possibility of altering the lipid profile and thus the risk of cardiovascular morbidity of UHR individuals. PMID- 26362579 TI - Interpersonal violence: quantifying the burden of injury in a South African trauma centre. AB - INTRODUCTION: Interpersonal violence is an epidemic in South Africa and remains an under-reported and expensive burden on health resources. In most of the developing world there is little or no descriptive information about the expense of treating the consequences of interpersonal violence. OBJECTIVE: To review the direct burden of interpersonal violence on a tertiary hospital in Northern KwaZulu-Natal, an area known to have high rates of poverty and violent crime. MATERIAL AND METHODS: A retrospective case note review of emergency hospital admissions between January and March 2013 was carried out. The reports included demographic characteristics, admitting diagnosis and surgical management. Case files were reviewed to determine cost drivers, such as radiological investigations, blood products, theatre usage and specialist care. RESULTS: Trauma accounted for 374 hospital admissions from the emergency department, of which 142 (38%) were attributable to interpersonal violence (16% of total admissions). One hundred and fifty-six hospital bed days were used over the study period. The average inpatient stay was 9.8 days with 58% requiring a resuscitation bed on admission. One-third of patients underwent emergency surgery and eight patients required postoperative intensive care. The minimum hospital expenditure for interpersonal violence injuries over 3 months was R8 367 788 ($783 960). DISCUSSION: Interpersonal violence is the source of a significant financial burden on the South African health system. Patients are often severely injured and require a high level of specialist investigations and surgical care. This study gives evidence to improve budget and workload planning for regional surgical departments and supports the need for more effective primary prevention. PMID- 26362580 TI - Psychological distress in medical patients seeking ED care for somatic reasons: results of a systematic literature review. AB - OBJECTIVES: The aim of this systematic literature review is to investigate (A) currently used instruments for assessing psychological distress, (B) the prevalence of psychological distress in medical emergency department (ED) patients with acute somatic conditions and (C) empirical evidence on how predictors are associated with psychological distress. METHODS: We conducted an electronic literature search using three databases to identify studies that used validated instruments for detection of psychological distress in adult patients presented to the ED with somatic (non-psychiatric) complaints. From a total of 1688 potential articles, 18 studies were selected for in-depth review. RESULTS: A total of 13 instruments have been applied for assessment of distress including screening questionnaires and briefly structured clinical interviews. Using these instruments, the prevalence of psychological distress detected in medical ED patients was between 4% and 47%. Psychological distress in general and particularly depression and anxiety have been found to be associated with demographic factors (eg, female gender, middle age) and illness-related variables (eg, urgency of triage category). Some studies reported that coexisting psychological distress of medical patients identified in the ED was associated with physical and psychological health status after ED discharge. Importantly, during routine clinical care, only few patients with psychological distress were diagnosed by their treating physicians. CONCLUSIONS: There is strong evidence that psychological distress is an important and prevalent cofactor in medically ill patients presenting to the ED with harmful associations with (subjective) health outcomes. To prove causality, future research should investigate whether screening and lowering psychological distress with specific interventions would result in better patient outcomes. PMID- 26362581 TI - Beyond triage: the diagnostic accuracy of emergency department nursing staff risk assessment in patients with suspected acute coronary syndromes. AB - OBJECTIVES: To establish the accuracy of emergency department (ED) nursing staff risk assessment using an established chest pain risk score alone and when incorporated with presentation high-sensitivity troponin testing as part of an accelerated diagnostic protocol (ADP). DESIGN: Prospective observational study comparing nursing and physician risk assessment using the modified Goldman (m Goldman) score and a predefined ADP, incorporating presentation high-sensitivity troponin. SETTING: A UK District ED. PATIENTS: Consecutive patients, aged >=18, with suspected cardiac chest pain and non-ischaemic ECG, for whom the treating physician determined serial troponin testing was required. OUTCOME MEASURES: 30 day major adverse cardiac events (MACE). RESULTS: 960 participants were recruited. 912/960 (95.0%) had m-Goldman scores recorded by physicians and 745/960 (77.6%) by nursing staff. The area under the curve of the m-Goldman score in predicting 30-day MACE was 0.647 (95% CI 0.594 to 0.700) for physicians and 0.572 (95% CI 0.510 to 0.634) for nursing staff (p=0.09). When incorporated into an ADP, sensitivity for the rule-out of MACE was 99.2% (95% CI 94.8% to 100%) and 96.7% (90.3% to 99.2%) for physicians and nurses, respectively. One patient in the physician group (0.3%) and three patients (1.1%) in the nursing group were classified as low risk yet had MACE. There was fair agreement in the identification of low-risk patients (kappa 0.31, 95% CI 0.24 to 0.38). CONCLUSIONS: The diagnostic accuracy of ED nursing staff risk assessment is similar to that of ED physicians and interobserver reliability between assessor groups is fair. When incorporating high-sensitivity troponin testing, a nurse-led ADP has a miss rate of 1.1% for MACE at 30 days. TRIAL REGISTRATION NUMBER: Controlled Trials Database (ISRCTN no. 21109279). PMID- 26362582 TI - Confirmation of suboptimal protocols in spinal immobilisation? AB - BACKGROUND: Spinal immobilisation during extrication of patients in road traffic collisions is routinely used despite the lack of evidence for this practice. In a previous proof of concept study (n=1), we recorded up to four times more cervical spine movement during extrication using conventional techniques than self controlled extrication. OBJECTIVE: The objective of this study was to establish, using biomechanical analysis which technique provides the minimal deviation of the cervical spine from the neutral in-line position during extrication from a vehicle in a larger sample of variable age, height and mass. METHODS: A crew of two paramedics and four fire-fighters extricated 16 immobilised participants from a vehicle using six techniques for each participant. Participants were marked with biomechanical sensors and relative movement between the sensors was captured via high-speed infrared motion analysis cameras. A three-dimensional mathematical model was developed and a repeated-measures analysis of variance was used to compare movement across extrication techniques. RESULTS: Controlled self extrication without a collar resulted in a mean movement of 13.33 degrees from the neutral in-line position of the cervical spine compared to a mean movement of 18.84 degrees during one of the equipment-aided extrications. Two equipment aided techniques had significantly higher movement (p<0.05) than other techniques. Both height (p=0.003) and mass (p=0.02) of the participants were significant independent predictors of movement. CONCLUSIONS: These data support the findings of the proof of concept study, for haemodynamically stable patients controlled self-extrication causes less movement of the cervical spine than extrications performed using traditional prehospital rescue equipment. PMID- 26362583 TI - Amyloidogenic Properties of Short alpha-L-Glutamic Acid Oligomers. AB - Poly-L-glutamic acid (PLGA) forms amyloid-like beta2-fibrils with the main spectral component of vibrational amide I' band unusually shifted below 1600 cm( 1). This distinct infrared feature has been attributed to the presence of bifurcated hydrogen bonds coupling C?O and N-D (N-H) groups of the main chains to glutamate side chains. Here, we investigate how decreasing the chain length of PLGA affects its capacity to form beta2-fibrils. A series of acidified aqueous solutions of synthetic (l-Glu)n peptides (n ~ 200, 10, 6, 5, 4, and 3) were incubated at high temperature. We observed that n = 4 is the critical chain length for which formation of aggregates with the beta2-like infrared features is still observed under such conditions. Interestingly, according to atomic force microscopy (AFM), the self-assembly of (L-Glu)n chains varying vastly in length produces fibrils with rather uniform diameters of approximately 4-6 nm. Kinetic experiments on (L-Glu)5 and (L-Glu)200 peptides indicate that the fibrillation is significantly accelerated not only in the presence of homologous seeds but also upon cross-seeding, suggesting thereby a common self-assembly theme for (L-Glu)n chains of various lengths. Our results are discussed in the context of mechanisms of amyloidogenic fibrillation of homopolypeptides. PMID- 26362575 TI - Meta-analysis of Genome-Wide Association Studies for Extraversion: Findings from the Genetics of Personality Consortium. AB - Extraversion is a relatively stable and heritable personality trait associated with numerous psychosocial, lifestyle and health outcomes. Despite its substantial heritability, no genetic variants have been detected in previous genome-wide association (GWA) studies, which may be due to relatively small sample sizes of those studies. Here, we report on a large meta-analysis of GWA studies for extraversion in 63,030 subjects in 29 cohorts. Extraversion item data from multiple personality inventories were harmonized across inventories and cohorts. No genome-wide significant associations were found at the single nucleotide polymorphism (SNP) level but there was one significant hit at the gene level for a long non-coding RNA site (LOC101928162). Genome-wide complex trait analysis in two large cohorts showed that the additive variance explained by common SNPs was not significantly different from zero, but polygenic risk scores, weighted using linkage information, significantly predicted extraversion scores in an independent cohort. These results show that extraversion is a highly polygenic personality trait, with an architecture possibly different from other complex human traits, including other personality traits. Future studies are required to further determine which genetic variants, by what modes of gene action, constitute the heritable nature of extraversion. PMID- 26362584 TI - Comparative validity of the Adult Attachment Interview and the Adult Attachment Projective. AB - The Adult Attachment Interview (AAI) and the Adult Attachment Projective (AAP) purport to measure the same attachment classifications. The aims of this study were to determine the concurrent validity of the AAI and AAP, and to compare their ability to predict indicators of risk associated with socioeconomic status (SES), depression, and 5-HTTLPR genotype. Results indicated no agreement between AAI and AAP attachment classifications in a sample of late adolescents. As predicted, individuals classified as "unresolved" with regard to loss or trauma were significantly more likely to be of lower SES, have higher levels of depression, and have the 5-HTTLPR "ss" genotype than individuals with secure, preoccupied, or dismissing attachments. These associations, however, were only significant when attachment was classified with the AAI. Results suggest that the AAI and AAP measure different facets of attachment as a result of their unique methodologies and coding criteria. Further research is needed to support their comparability before investigators can assume that the AAP is a valid substitute for the AAI. PMID- 26362585 TI - Lipid nanocapsules for behavioural testing in aquatic toxicology: Time-response of Eurytemora affinis to environmental concentrations of PAHs and PCB. AB - The increasing interest for behavioural investigations in aquatic toxicology has heightened the need for developing tools that allow realistic exposure conditions and provide robust quantitative data. Calanoid copepods dominate the zooplankton community in marine and brackish environments. These small organisms have emerged as attractive models because of the sensitivity of their behaviour to important environmental parameters and the significance of self-induced motion in their ecology. Estuarine copepods are particularly relevant in this context because of their incessant exposure to high levels of pollution. We used lipid nanocapsules to deliver sub-lethal concentrations of PAHs (pyrene, phenanthrene and fluoranthene) and PCB 153 into the digestive track of males and females Eurytemora affinis. This novel approach enabled us to achieve both contact and trophic exposure without using phytoplankton, and to expose copepods to small hydrophobic molecules without using organic solvent. We reconstructed the motion of many copepods swimming simultaneously by means of three-dimensional particle tracking velocimetry. We quantified the combined effects of contact and trophic toxicity by comparing the kinematic and diffusive properties of their motion immediately and after 3h and 24h of exposure. Despite the lack of toxicity of their excipients, both empty and loaded capsules increased swimming activity and velocity immediately after exposure. Laser microscopy imaging shows adhesion of nanocapsules on the exoskeleton of the animals, suggesting contact toxicity. The behavioural response resembles an escape reaction allowing copepods to escape stressful conditions. The contact toxicity of empty capsules and pollutants appeared to be additive and nanocapsules loaded with PCB caused the greatest effects. We observed a progressive accumulation of capsules in the digestive track of the animals after 3h and 24h of exposure, which suggests an increasing contribution of systemic toxicity. Nanocapsules filled with PAHs caused a smaller response compared to empty capsules, which we attribute to the narcotic properties of these toxicants. The sharp decrease in velocity after 24h of exposure to capsules loaded with PCB suggests physiological incapacitation following systemic toxicity. Clear differences are visible between genders in their response to empty and loaded capsules, for all exposure durations. Females appear to be less sensitive than males, suggesting different tolerance to stress conditions. Our results confirm the feasibility of using lipid nanocapsules to identify pollutant-induced behavioural alteration in the plankton. They also add new insights into the contact and systemic toxicity of common pollutants. We expect that our results will assist and evoke further research to develop suitable nanocarrier systems for behavioural testing. PMID- 26362586 TI - The efficacy of polycaprolactone/hydroxyapatite scaffold in combination with mesenchymal stem cells for bone tissue engineering. AB - Major drawbacks of using an autograft are the possibilities of insufficient bony source and patient's morbidity after operation. Bone tissue engineering technology, therefore, has been applied for repairing bony defects. Previous study showed that a novel fabricated 3D-Polycaprolactone/Hydroxyapatite (PCL/HAp) scaffold possessed a good biocompatibility for bone cells. This study aimed to determine the ability of PCL/HAp for supporting cell growth, gene expression, and osteogenic differentiation in three types of mesenchymal stem cells, including bone marrow-derived mesenchymal stem cells (BMSCs), dental pulp stem cells (DPSCs), and adiposed-derived mesenchymal stem cells (ADSCs). These were assessed by cell viability assay (MTT), reverse-transcription polymerase chain reaction (RT-PCR) analysis, alkaline phosphatase activity, and osteogenic differentiation by alizarin red-S staining. The results showed that PCL/HAp scaffold could support growth of all three types of mesenchymal stem cells. In addition, DPSCs with PCL/HAp showed the highest level of calcium deposition compared to other groups. In conclusion, DPSCs exhibited a better compatibility with these scaffolds compared to BMSCs and ADSCs. However, the PCL/HAp could be a good candidate scaffold for all tested mesenchymal stem cells in bone tissue engineering. PMID- 26362587 TI - Prognostic effect of hENT1, dCK and HuR expression by morphological type in periampullary adenocarcinoma, including pancreatic cancer. AB - BACKGROUND: Putative biomarkers of gemcitabine response have been extensively studied in pancreatic cancer, but less so in other types of periampullary adenocarcinoma. The most studied biomarker is human equilibrative nucleoside transporter 1 (hENT1), and the activating enzyme deoxycytidine kinase (dCK) has also been linked to treatment response. The RNA-binding protein human antigen R (HuR) has been demonstrated to confer increased dCK levels in vitro and to predict gemcitabine response in vivo. Here, we investigated the prognostic impact of hENT1, dCK and HuR in pancreatobiliary (PB) and intestinal (I) type periampullary cancers, respectively. MATERIAL AND METHODS: Immunohistochemical expression of hENT1, dCK and HuR was evaluated in tissue microarrays with all primary tumours and 103 paired lymph node metastases from a consecutive retrospective cohort of 175 patients with resected periampullary adenocarcinomas. RESULTS: In patients with PB-type tumours, neither hENT1 nor dCK expression was prognostic. A high HuR cytoplasmic/nuclear ratio was associated with a significantly reduced five-year overall survival (OS) in patients receiving adjuvant gemcitabine (HR 2.07, 95% CI 1.03-4.17) but not in untreated patients (pinteraction = 0.028). In patients with I-type tumours receiving adjuvant chemotherapy, high dCK expression was significantly associated with a prolonged recurrence-free survival (RFS) (HR 0.09, 95% CI 0.01-0.73, pinteraction = 0.023). Furthermore, HuR expression was associated with a prolonged OS and RFS in unadjusted but not in adjusted analysis and hENT1 expression was an independent predictor of a prolonged RFS (HR 0.24, 95% CI 0.10-0.59), regardless of adjuvant treatment. CONCLUSION: hENT1 expression is a favourable prognostic factor in I type, but not in PB-type tumours. High dCK expression is a favourable prognostic factor in patients with I-type tumours receiving adjuvant treatment and a high cytoplasmic/nuclear HuR ratio is a negative prognostic factor in gemcitabine treated PB-type tumours. Morphological subtype should always be considered in biomarker studies on periampullary cancer. PMID- 26362589 TI - Intestinal ultrasonography in infants with moderate or severe hypoxic-ischemic encephalopathy receiving hypothermia. AB - BACKGROUND: Infants with hypoxic-ischemic encephalopathy (HIE) may develop multiorgan dysfunction, but assessment of intestinal involvement is imprecise and based on nonspecific clinical signs that may occur several days later. Ultrasound imaging has been described as a helpful tool in assessing intestinal involvement in many gastrointestinal disorders. OBJECTIVE: Describe abdominal ultrasonography findings in infants receiving therapeutic hypothermia and investigate its association with the severity of the hypoxic-ischemic insult and death. MATERIALS AND METHODS: Studies were performed within the first 36 h of life to assess intestinal appearance (normal bowel, bowel wall echogenicity and thickness, and sloughed mucosa), free fluid, peristalsis and intramural perfusion. These findings were compared between infants with moderate and severe encephalopathy. Ultrasound findings were also categorized in three major groups and compared with markers of severity of the hypoxic-ischemic insult and with mortality. RESULTS: Nineteen infants with moderate and 9 with severe HIE at admission were studied (17.7 +/- 9.5 h of life). Major ultrasonography findings were increased bowel wall echogenicity (78%), free fluid (75%), decreased or absent peristalsis (50%) and sloughing of the intestinal mucosa (21%). Abnormal intestinal findings such as increased bowel wall echogenicity in all quadrants and presence of sloughed mucosa were associated with more severe hypoxic-ischemic insult. All 12 patients with normal bowel appearance or increased bowel wall echogenicity restricted to only one quadrant survived, whereas 7/15 (47%) patients with increased bowel wall echogenicity in all four quadrants died during hospitalization. The presence of sloughed mucosa was associated with increased mortality (P < 0.001). CONCLUSION: In infants receiving therapeutic hypothermia, a high prevalence of intestinal involvement was noted by using ultrasonographic assessment. An association between intestinal findings and severity of hypoxic-ischemic insult was observed. The presence of sloughed mucosa is a potential ultrasonographic sign of severity. PMID- 26362588 TI - A time to be stressed? Time perspectives and cortisol dynamics among healthy adults. AB - Perceptions of past, present, and future events may be related to stress pathophysiology. We assessed whether Time Perspective (TP) is associated with cortisol dynamics among healthy adults (N=61, Ages=18-35, M=22.9, SD=4.1) exposed to the Trier Social Stress Test (TSST). TP was measured according to two profiles: maladaptive Deviation from Balanced TP (DBTP) and adaptive Deviation from Negative TP (DNTP). Eight salivary cortisol samples were analyzed using area under the curve with respect to ground (AUCg) and to increase (AUCi). Statistic analyses involved partial correlations controlling for depressive symptoms. Results for both sexes showed that higher DBTP scores were associated with lower cortisol AUCg scores, while higher DNTP scores were associated with higher cortisol AUCg scores. These novel findings suggest that maladaptive TP profiles influence hypocortisolism, whereas adaptive TP profiles influence hypercortisolism. Thus, TP profiles may impact conditions characterized by altered cortisol concentrations. PMID- 26362590 TI - Early vs. late reverse ventricular remodeling in patients with cardiomyopathy. AB - BACKGROUND: Predictors of left ventricular reverse remodeling (LVRR) and differences in the time taken to achieve LVRR remain unclear. METHODS: We consecutively registered 129 patients with severe cardiomyopathy admitted with heart failure (HF). Patients were followed for a median of 778.0 days (IQ: 457.0, 1078.0). LVRR was defined as a decrease in indexed left ventricular systolic dimension of at least 15% additional to a 25% improvement in left ventricular ejection fraction at outpatient check-up compared with discharge. LVRR accomplishment within 400 days was defined as early-LVRR opposing the remaining late-LVRR patients. Primary endpoint was a composite of all-cause mortality and HF re-hospitalization. RESULTS: LVRR was observed in 51 patients (39.5%). Baseline predictors for LVRR were age younger than 60 years (OR, 3.27; 95% CI 1.04-10.37, p=0.043), no history of previous HF hospitalization (OR, 0.32; 95% CI 0.12-0.86, p=0.025), and systolic blood pressure (sBP) >100mmHg at discharge (OR, 4.39; 95% CI 1.39-13.81, p=0.011). Overall, there were 51 endpoint events [LVRR 11 (21.6%) vs. non-LVRR 40 (49.4%), p<0.001]. LVRR was a significant predictor of favorable prognosis (HR, 3.77; 95% CI 1.68-8.47, p<0.001). Notably, 41 (80.4%) patients qualified for early-LVRR. Early-LVRR was associated with better prognosis compared with late-LVRR [early-LVRR 6 (14.6%) vs. late-LVRR 5 (50.0%), p=0.066]. Among assessed variables, sBP >100mmHg at discharge was a significant predictor of early-LVRR (OR, 10.87; 95% CI 1.19-100.0, p=0.034). CONCLUSION: Prognosis was improved in patients who achieved LVRR. Early-LVRR tended to be an advantage in terms of long-term prognosis. Higher sBP was a predictor not only for all-LVRR but also early-LVRR. PMID- 26362591 TI - Author's reply. PMID- 26362592 TI - Esthetic prosthodontic treatment - The state-of-the-art. PMID- 26362593 TI - Relationships between perceived chewing ability, objective masticatory function and oral health-related quality of life in mandibulectomy or glossectomy patients with a dento-maxillary prosthesis. AB - PURPOSE: This preliminary study examined whether the type of surgery performed for head and neck lesion was associated perceived chewing ability, objective masticatory function, and oral health-related quality of life (OHRQoL) in patients who required a dento-maxillary prosthesis postoperatively. METHODS: Thirty-eight patients with a dento-maxillary prosthesis were divided into three groups according to the type of surgery received: marginal mandibulectomy, segmental mandibulectomy with bony reconstruction, or glossectomy. Perceived chewing ability, objective mixing ability, and OHRQoL were evaluated using a food intake questionnaire, color-changeable chewing gum, and the Geriatric Oral Health Assessment Index (GOHAI), respectively. Differences in the scores obtained by the three measures were compared between the surgical groups using the Kruskal-Wallis test, and associations between the scores in each group were analyzed by Spearman's rank correlation analysis. RESULTS: Objective mixing ability was found to be significantly low only in patients who underwent glossectomy. No other measures differed significantly between the surgical groups. Perceived chewing ability and objective mixing ability were significantly associated in the marginal mandibulectomy and glossectomy groups but not in the segmental mandibulectomy group. Furthermore, GOHAI score was significantly associated with perceived chewing ability and objective mixing ability in the marginal mandibulectomy group. CONCLUSIONS: Within the limitations of this study, the present findings suggest that the type of surgery received might influence food mixing ability. Associations among food mixing ability, perceived chewing and OHRQoL are not accountable depending on the type of surgery received, indicating the presence of other contributing factors to be considered. PMID- 26362594 TI - NICE recommends tighter blood sugar control in diabetes to reduce risk of complications. PMID- 26362595 TI - Ibrutinib-A double-edge sword in cancer and autoimmune disorders. AB - Targeted therapies have appeared as new treatment options for several disease types, including cancer and autoimmune disorders. Of several targets, tyrosine kinases (TKs) are among the most promising. Overexpression of TKs provides a target for novel therapeutic agents, including small molecule inhibitors of tyrosine kinases (TKI). Ibrutinib (PCI-32765) is a TKI of Bruton's tyrosine kinase (Btk), a key kinase of the B-cell receptor signaling pathway that plays a significant role in the proliferation, differentiation and survival of B cells. In addition to inhibitory effects, recent studies have shown that ibrutinib has multiple immunomodulatory effects. It binds covalently to IL-2 inducible tyrosine kinase (Itk) in T lymphocytes and suppresses the survival of T-helper (Th) 2 cells. This changes the balance of Th1/Th2 cells toward Th1 subset, which are the main immune cells targeting tumor cells. The dual activity of ibrutinib has paid a great attention and several studies are evaluating the anti-tumor and immunomodulatory effects in cancer, autoimmune disorders and infectious diseases. In this article we review the inhibitory and immunomodulatory effects of ibrutinib in B-cell malignancies, autoimmune diseases and infections, as well as the communication between the Ror1 receptor tyrosine kinase and BCR and effects of ibrutinib on this crosstalk. PMID- 26362597 TI - Trajectories of decline in cognition and daily functioning in preclinical dementia. AB - INTRODUCTION: Although preclinical dementia is characterized by decline in cognition and daily functioning, little is known on their temporal sequence. We investigated trajectories of cognition and daily functioning in preclinical dementia, during 18 years of follow-up. METHODS: In 856 dementia cases and 1712 controls, we repetitively assessed cognition and daily functioning with memory complaints, mini-mental state examination (MMSE), instrumental activities of daily living (IADL), and basic activities of daily living (BADL). RESULTS: Dementia cases first reported memory complaints 16 years before diagnosis, followed by decline in MMSE, IADL, and finally BADL. Vascular dementia related to earlier decline in daily functioning but later in cognition, compared with Alzheimer's disease. Higher education related to larger preclinical cognitive decline, whereas apolipoprotein E (APOE) epsilon4 carriers declined less in daily functioning. DISCUSSION: These results emphasize the long hierarchical preclinical trajectory of functional decline in dementia. Furthermore, they show that various pathologic, environmental, and genetic factors may influence these trajectories of decline. PMID- 26362596 TI - The pattern of amyloid accumulation in the brains of adults with Down syndrome. AB - INTRODUCTION: Adults with Down syndrome (DS) invariably develop Alzheimer's disease (AD) neuropathology. Understanding amyloid deposition in DS can yield crucial information about disease pathogenesis. METHODS: Forty-nine adults with DS aged 25-65 underwent positron emission tomography with Pittsburgh compound-B (PIB). Regional PIB binding was assessed with respect to age, clinical, and cognitive status. RESULTS: Abnormal PIB binding became evident from 39 years, first in striatum followed by rostral prefrontal-cingulo-parietal regions, then caudal frontal, rostral temporal, primary sensorimotor and occipital, and finally parahippocampal cortex, thalamus, and amygdala. PIB binding was related to age, diagnostic status, and cognitive function. DISCUSSION: PIB binding in DS, first appearing in striatum, began around age 40 and was strongly associated with dementia and cognitive decline. The absence of a substantial time lag between amyloid accumulation and cognitive decline contrasts to sporadic/familial AD and suggests this population's suitability for an amyloid primary prevention trial. PMID- 26362598 TI - Solanocapsine derivatives as potential inhibitors of acetylcholinesterase: Synthesis, molecular docking and biological studies. AB - The investigation of natural products in medicinal chemistry is essential today. In this context, acetylcholinesterase (AChE) inhibitors comprise one type of the compounds most actively studied in the search for an effective treatment of symptoms of Alzheimer's disease. This work describes the isolation of a natural compound, solanocapsine, the preparation of its chemical derivatives, the evaluation of AChE inhibitory activity, and the structure-activity analysis of relevant cases. The influence of structural variations on the inhibitory potency was carefully investigated by modifying different reactive parts of the parent molecule. A theoretical study was also carried out into the binding mode of representative compounds to the enzyme through molecular modeling. The biological properties of the series were investigated. Through this study valuable information was obtained of steroidal alkaloid-type compounds as a starting point for the synthesis of AChE inhibitors. PMID- 26362599 TI - Induction of hormone-sensitive lipase/cholesteryl esterase gene expression by C/EBPalpha independently of the PKA pathway in the adrenocortical Y-1 cells. AB - The effect of C/EBPalpha on the expression of LIPE gene encoding hormone sensitive lipase/cholesteryl esterase (HSL) was investigated in Y-1 CCL79 cells. It was found that transfection of these cells with the vector overexpressing C/EBPalpha increased both the level of LIPE transcript, measured by RT-qPCR, and the luminesce emitted by luciferase reporter gene fused to the -2150 fragment of LIPE promoter. Activation of adenylyl cyclase by forskolin resulted in 2.5-fold increase in the intensity of luminescence and over 3-fold increase in luminescence was observed when the cells were cotransfected with the vector overexpressing C/EBP. The incubation of C/EBP-cotransfected cells with forskolin caused over 6-fold increase in the intensity of luminescence, suggesting that the effects of C/EBPalpha and forskolin are additive. The analysis of sequence of the proximal LIPE promoter showed multiple binding sites for various transcription factors including C/EBPalpha site, which is located between nucleotides -46 bp and -59 bp. When the Y-1 cells were transfected with the recombinant vector containing -60 bp fragment of LIPE promoter fused to the luciferase reporter gene and were cotransfected with the vector overexpressing C/EBPalpha, the luminescence increases about 9-fold indicating that C/EBPalpha stimulates the expression of LIPE by reacting with its response element. The results indicate that C/EBPalpha stimulates the expression of LIPE independently of the PKA pathway by binding to a response element situated within the -60 bp fragment of LIPE promoter. This suggests that C/EBPalpha might be involved in the regulation of LIPE expression and thus cholesterol supply for steroid hormone synthesis. PMID- 26362600 TI - Unveiling the molecular mechanism of brassinosteroids: Insights from structure based molecular modeling studies. AB - Brassinosteroid (BR) phytohormones play indispensable roles in plant growth and development. Brassinolide (BL) and 24-epibrassinolide (24-epiBL) are the most active ones among the BRs reported thus far. Unfortunately, the extremely low natural content and intricate synthesis process limit their popularization in agricultural production. Earlier reports to discover alternative compounds have resulted in molecules with nearly same scaffold structure and without diversity in chemical space. In the present study, receptors structure based BRs regulation mechanism was analyzed. First, we examined the detailed binding interactions and their dynamic stability between BL and its receptor BRI1 and co-receptor BAK1. Then, the binding modes and binding free energies for 24-epiBL and a series of representative BRs binding with BRI1 and BRI1-BAK1 were carried out by molecular docking, energy minimization and MM-PBSA free energy calculation. The obtained binding structures and energetic results provided vital insights into the structural factors affecting the activity from both receptors and BRs aspects. Subsequently, the obtained knowledge will serve as valuable guidance to build pharmacophore models for rational screening of new scaffold alternative BRs. PMID- 26362601 TI - Vascular Health and Genetic Risk Affect Mild Cognitive Impairment Status and 4 Year Stability: Evidence From the Victoria Longitudinal Study. AB - OBJECTIVES: Mild cognitive impairment (MCI) is a high-risk condition for progression to Alzheimer's disease (AD). Vascular health is a key mechanism underlying age-related cognitive decline and neurodegeneration. AD-related genetic risk factors may be associated with preclinical cognitive status changes. We examine independent and cross-domain interactive effects of vascular and genetic markers for predicting MCI status and stability. METHOD: We used cross sectional and 2-wave longitudinal data from the Victoria Longitudinal Study, including indicators of vascular health (e.g., reported vascular diseases, measured lung capacity and pulse rate) and genetic risk factors-that is, apolipoprotein E (APOE; rs429358 and rs7412; the presence vs absence of epsilon4) and catechol-O-methyltransferase (COMT; rs4680; met/met vs val/val). We examined associations with objectively classified (a) cognitive status at baseline (not impaired congnitive (NIC) controls vs MCI) and (b) stability or transition of cognitive status across a 4-year interval (stable NIC-NIC vs chronic MCI-MCI or transitional NIC-MCI). RESULTS: Using logistic regression, indicators of vascular health, both independently and interactively with APOE epsilon4, were associated with risk of MCI at baseline and/or associated with MCI conversion or MCI stability over the retest interval. DISCUSSION: Several vascular health markers of aging predict MCI risk. Interactively, APOE epsilon4 may intensify the vascular health risk for MCI. PMID- 26362603 TI - Ageism Comes of Age. PMID- 26362604 TI - The quality gap in mental health treatment in Australia. PMID- 26362602 TI - Marianismo and Caregiving Role Beliefs Among U.S.-Born and Immigrant Mexican Women. AB - OBJECTIVES: We aimed to explore how women of Mexican-origin conceptualized caregiving as a construct in terms of cultural beliefs, social norms, role functioning, and familial obligations. We examined the personal experiences of U.S-born and immigrant Mexican female caregivers to identify how these 2 groups differed in their views of the caregiver role. METHODS: We conducted 1-time in depth interviews with 44 caregivers living in Southern California. Our study was guided by marianismo, a traditional role occupied by women in the Mexican family. We analyzed data from a grounded theory approach involving the constant comparative method to refine and categorize the data. RESULTS: The majority of all caregivers had similar views about caregiving as an undertaking by choice, and almost all caregivers engaged in self-sacrificing actions to fulfill the marianismo role. Despite these similarities, U.S.-born and immigrant caregivers used different words to describe the same concepts or assigned different meanings to other key aspects of caregiving, suggesting that these 2 groups had different underlying motivations for caregiving and orientations to the role. DISCUSSION: Our findings highlight the complexity of language and culture in underlying caregiving concepts, making the concepts challenging to operationalize and define in a heterogeneous sample of Latinos. PMID- 26362605 TI - Are there any situations where community treatment orders are effective? PMID- 26362608 TI - Correction. PMID- 26362606 TI - Arabidopsis SEIPIN Proteins Modulate Triacylglycerol Accumulation and Influence Lipid Droplet Proliferation. AB - The lipodystrophy protein SEIPIN is important for lipid droplet (LD) biogenesis in human and yeast cells. In contrast with the single SEIPIN genes in humans and yeast, there are three SEIPIN homologs in Arabidopsis thaliana, designated SEIPIN1, SEIPIN2, and SEIPIN3. Essentially nothing is known about the functions of SEIPIN homologs in plants. Here, a yeast (Saccharomyces cerevisiae) SEIPIN deletion mutant strain and a plant (Nicotiana benthamiana) transient expression system were used to test the ability of Arabidopsis SEIPINs to influence LD morphology. In both species, expression of SEIPIN1 promoted accumulation of large sized lipid droplets, while expression of SEIPIN2 and especially SEIPIN3 promoted small LDs. Arabidopsis SEIPINs increased triacylglycerol levels and altered composition. In tobacco, endoplasmic reticulum (ER)-localized SEIPINs reorganized the normal, reticulated ER structure into discrete ER domains that colocalized with LDs. N-terminal deletions and swapping experiments of SEIPIN1 and 3 revealed that this region of SEIPIN determines LD size. Ectopic overexpression of SEIPIN1 in Arabidopsis resulted in increased numbers of large LDs in leaves, as well as in seeds, and increased seed oil content by up to 10% over wild-type seeds. By contrast, RNAi suppression of SEIPIN1 resulted in smaller seeds and, as a consequence, a reduction in the amount of oil per seed compared with the wild type. Overall, our results indicate that Arabidopsis SEIPINs are part of a conserved LD biogenesis machinery in eukaryotes and that in plants these proteins may have evolved specialized roles in the storage of neutral lipids by differentially modulating the number and sizes of lipid droplets. PMID- 26362607 TI - The Birth of a Black Rice Gene and Its Local Spread by Introgression. AB - The origin and spread of novel agronomic traits during crop domestication are complex events in plant evolution. Wild rice (Oryza rufipogon) has red grains due to the accumulation of proanthocyanidins, whereas most cultivated rice (Oryza sativa) varieties have white grains induced by a defective allele in the Rc basic helix-loop-helix (bHLH) gene. Although the events surrounding the origin and spread of black rice traits remain unknown, varieties with black grains due to anthocyanin accumulation are distributed in various locations throughout Asia. Here, we show that the black grain trait originated from ectopic expression of the Kala4 bHLH gene due to rearrangement in the promoter region. Both the Rc and Kala4 genes activate upstream flavonol biosynthesis genes, such as chalcone synthase and dihydroflavonol-4-reductase, and downstream genes, such as leucoanthocyanidin reductase and leucoanthocyanidin dioxygenase, to produce the respective specific pigments. Genome analysis of 21 black rice varieties as well as red- and white-grained landraces demonstrated that black rice arose in tropical japonica and its subsequent spread to the indica subspecies can be attributed to the causal alleles of Kala4. The relatively small size of genomic fragments of tropical japonica origin in some indica varieties indicates that refined introgression must have occurred by natural crossbreeding in the course of evolution of the black trait in rice. PMID- 26362611 TI - Extra-endoscopic mechanical lithotripsy of an impacted gallstone passing in the duodenum through a cholecystoduodenal fistula. PMID- 26362609 TI - Non-autonomous overgrowth by oncogenic niche cells: Cellular cooperation and competition in tumorigenesis. AB - Tumor progression is classically viewed as the Darwinian evolution of subclones that sequentially acquire genetic mutations and autonomously overproliferate. However, growing evidence suggests that tumor microenvironment and subclone heterogeneity contribute to non-autonomous tumor progression. Recent Drosophila studies revealed a common mechanism by which clones of genetically altered cells trigger non-autonomous overgrowth. Such "oncogenic niche cells" (ONCs) do not overgrow but instead stimulate neighbor overgrowth and metastasis. Establishment of ONCs depends on competition and cooperation between heterogeneous cell populations. This review characterizes diverse ONCs identified in Drosophila and describes the genetic basis of non-autonomous tumor progression. Similar mechanisms may contribute to mammalian cancer progression and recurrence. PMID- 26362610 TI - PAX8 pathogenic variants in Chinese patients with congenital hypothyroidism. AB - BACKGROUND: The clinical presentation of patients with congenital hypothyroidism (CH) caused by paired box gene 8 (PAX8) pathogenic variants is variable and PAX8 mutation rates differ significantly among different populations. This study was set to examine the PAX8 mutation spectrum and prevalence among patients with CH in Guangxi Zhuang Autonomous Region, China. METHODS: Peripheral venous blood samples were collected from the patients. Genomic DNA was extracted from peripheral blood leukocytes. All exons of the 11 known CH associated genes including PAX8 together with their exon-intron boundaries were screened by next generation sequencing (NGS). Permanent or transient CH was determined using the results of thyroid function tests after temporary withdrawal of L-thyroxine (L T4) therapy at approximately 2 years of age. RESULTS: Next generation sequencing analysis of PAX8 in 378 CH patients revealed five different mutations in nine individuals (two are siblings). The mutations included two known missense variants, namely c.92G>A (p.R31H) and c.91C>T (p.R31C), and one novel missense variant c.68G>T (p.G23V), as well as two novel nonsense variants c.1090C>T (p. R364X) and c.658C>T (p.R220X). The variant c.92G>A (p.R31H) is highly recurrent in our patient cohort but the clinical phenotypes vary greatly among those carrying this variant. PAX8 pathogenic variants were mainly associated with permanent CH. CONCLUSION: The prevalence of PAX8 pathogenic variants was 2.38% among patients with CH in Guangxi. Our study expanded the PAX8 mutation spectrum and provided the best estimation of PAX8 mutation rate among CH patients in Guangxi, China. PMID- 26362612 TI - Asymptomatic true gallbladder duplication. PMID- 26362613 TI - Manually calculated oesophageal bolus clearance time increases in parallel with reflux severity at impedance-pH monitoring. AB - BACKGROUND: Oesophageal clearance has been scarcely studied. AIMS: Oesophageal clearance in endoscopy-negative heartburn was assessed to detect differences in bolus clearance time among patients sub-grouped according to impedance-pH findings. METHODS: In 118 consecutive endoscopy-negative heartburn patients impedance-pH monitoring was performed off-therapy. Acid exposure time, number of refluxes, baseline impedance, post-reflux swallow-induced peristaltic wave index and both automated and manual bolus clearance time were calculated. Patients were sub-grouped into pH/impedance positive (abnormal acid exposure and/or number of refluxes) and pH/impedance negative (normal acid exposure and number of refluxes), the former further subdivided on the basis of abnormal/normal acid exposure time (pH+/-) and abnormal/normal number of refluxes (impedance+/-). RESULTS: Poor correlation (r=0.35) between automated and manual bolus clearance time was found. Manual bolus clearance time progressively decreased from pH+/impedance+ (42.6s), pH+/impedance- (27.1s), pH-/impedance+ (17.8s) to pH /impedance- (10.8s). There was an inverse correlation between manual bolus clearance time and both baseline impedance and post-reflux swallow-induced peristaltic wave index, and a direct correlation between manual bolus clearance and acid exposure time. A manual bolus clearance time value of 14.8s had an accuracy of 93% to differentiate pH/impedance positive from pH/impedance negative patients. CONCLUSIONS: When manually measured, bolus clearance time reflects reflux severity, confirming the pathophysiological relevance of oesophageal clearance in reflux disease. PMID- 26362614 TI - Acetaminophen metabolism after liver resection: A prospective case-control study. AB - BACKGROUND: The effect of liver resection on acetaminophen metabolism and whether it is affected by residual liver volume is poorly understood. METHODS: We investigated the effects of liver resection on acetaminophen metabolism in a single centre, prospective observational, case-control study of inpatients. Patients undergoing liver resection were administered therapeutic post-operative acetaminophen. Glutathione and urinary acetaminophen metabolites were measured over the first three post-operative days and compared between patients with low (Group A) and high (Group B) residual liver volume. RESULTS: 41 patients (41% female, median age 62 [IQR 53-72] years) were included. Mean urinary cysteine levels increased significantly from post-operative day 1 to 2 (578.0 mg/day 95% CI 478.9-677.1 vs. 775.4 mg/day, 95% CI 625.7-925.1; p=0.03). Group A (n=11) had significantly higher median levels of cysteine (day 1, 464.3 mg/day [IQR 355.6 582.0]; day 3, 717.6 mg/day [IQR 423.5-1104.0]) compared to Group B (n=11): day 1, 545.4 mg/day (IQR 346.9-843.5); day 3, 508.1mg/day (IQR 390.8-788.4; p=0.048). No significant difference was observed in glutathione or 5-oxoproline levels between the groups. CONCLUSION: Low residual liver volume results in altered acetaminophen metabolism, however, no evidence of glutathione deficiency was observed. Therapeutic acetaminophen is safe after major liver resection provided liver function is adequate. PMID- 26362615 TI - Efficacy of air polishing for the non-surgical treatment of peri-implant diseases: a systematic review. AB - FOCUSED QUESTION: In patients suffering from peri-implant diseases, what is the efficacy of air polishing on changing signs of inflammation compared with control treatments (i.e. alternative measures for plaque removal with or without adjunctive antiseptic and/ or antibiotic therapy)? MATERIAL & METHODS: After electronic database and hand search, 10 full-text articles were independently screened by two reviewers. Finally, a total of five studies (six publications) fulfilled the inclusion criteria. The weighted mean difference (WMD) [p; 95% CI] in bleeding on probing- (BOP) (primary outcome) and probing pocket depth- (PD) reductions was estimated using a random effect model. RESULTS: All studies reported on residual BOP scores after therapy. A narrative data synthesis did not reveal any major improvement of bleeding index/ BOP or disease resolution following air polishing over mechanical debridement at mucositis sites. At peri implantitis sites, WMD in BOP reduction between test and control (mechanical debridement with or without local antiseptic therapy, Er:YAG laser) groups was 23.83% [p = 0.048; 95% CI (-47.47, -0.20)] favouring air polishing over control measures. CONCLUSIONS: While glycine powder air polishing is as effective as the control treatments at mucositis sites, it may improve the efficacy of non surgical treatment of peri-implantitis over the control measures investigated. A complete disease resolution was commonly not obtained. PMID- 26362617 TI - Carotid Artery Stenting (CAS) Outcomes May Vary between Operators and/or Institutions. The Results from Centers of CAS Excellence May Not Be Generalizable. PMID- 26362616 TI - Treatment of Basal Cell Carcinoma Using a One-Stop-Shop With Reflectance Confocal Microscopy: Study Design and Protocol of a Randomized Controlled Multicenter Trial. AB - BACKGROUND: Basal cell carcinoma (BCC) is the most common cancer diagnosed in white populations worldwide. The rising incidence of BCC is becoming a major worldwide public health problem. Therefore, there is a need for more efficient management. OBJECTIVE: The aim of this research is to assess the efficacy and safety of a one-stop-shop (OSS) concept, using real-time in vivo reflectance confocal microscopy (RCM) (Vivascope 1500; Lucid Technologies, Henrietta, NY, USA) as a diagnostic tool, prior to surgical management of new primary BCCs. METHODS: This is a prospective non-inferiority multi-center RCT designed to compare the "OSS concept using RCM" to current standards of care in diagnosing and treating clinically suspected BCC. Patients >= 18 years attending our outpatient clinic at the Department of Dermatology, Academic Medical Center, University of Amsterdam, and the Department of Dermatology, the Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital (Amsterdam, The Netherlands) with a clinically suspected new primary BCC lesion will be considered for enrollment using predefined inclusion and exclusion criteria, and will be randomly allocated to the experimental or control group. The main outcome parameter is the assessment of incomplete surgical excision margins on the final pathology report of confirmed BCC lesions (either by punch biopsy or RCM imaging). Other outcome measures include diagnostic accuracy (sensitivity and specificity) of RCM for diagnosing BCC and dividing between subtypes, and throughput time. Patient satisfaction data will be collected postoperatively after 3 months during routine follow-up. RESULTS: This research is investigator initiated and received ethics approval. Patient recruitment started in February 2015, and we expect all study-related activities to be completed by fall 2015. CONCLUSIONS: This RCT is the first to examine an OSS concept using RCM for diagnosing and treating clinically suspected BCC lesions. Results of this research are expected to have applications in evidence-based practice for the increasing number of patients suffering from BCC and possibly lead to a more efficient disease management strategy. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02285790; https://clinicaltrial.gov/ct2/show/NCT02285790 (Archived by WebCite at http://www.webcitation.org/6b2LfDKWu). PMID- 26362618 TI - Intravascular Leiomyomatosis with Intracardiac Extension. AB - Intravenous leiomyomatosis (IVL) is a rare nonmalignant tumor defined as a benign smooth muscle cell neoplasia in the veins. Patients with IVL may present with symptoms of a uterine leiomyoma such as pelvic pain and vaginal bleeding, or cardiorespiratory symptoms, including dyspnea and leg swelling. We report the case of a 65-year-old otherwise healthy Caucasian woman. Past medical history consisted of hysterectomy and left salpingo-oophorectomy 15 years before for multiple uterine fibromyomas associated with leiomyoma of vascular origin. A thoracoabdominal computed tomography (CT) scan confirmed the presence of a mass, measuring 76 * 37 * 44 mm, arising from the inferior vena cava (IVC) at the level of the left renal vein extending all the way into the right atrium and right ventricle. At laparotomy, a tumoral mass was excised from the left broad ligament up to the left renal vein and from the IVC up to its retrohepatic tract. Sternotomy was performed and cardiopulmonary bypass (CPB) was established among ascending aorta, upper vena cava, and right common femoral vein. After atriotomy, a voluminous and firm mass was excised from the right atrium, down to the level of the IVC. CPB was maintained for 80 min. Perioperative transfusion included two plasma and two red blood cells units. No adjuvant treatment was administered. Follow-up with annual CT scans was performed. Patient had no signs of recurrence after 3 years. PMID- 26362619 TI - Concomitant Vascular War Trauma Saturating a French Forward Surgical Team Deployed to Support the Victims of the Syrian War (2013). Interest of the Vascular Damage Control. AB - Vascular injuries from war require an emergency treatment whose objective is to quickly obtain hemostasis and the restoration of arterial flow. In this context of heavy trauma and limited means, damage control surgery is recommended and is based on the use of temporary vascular shunts (TVSs). We report the management of the simultaneous arrival of 2 vascular injuries of war in a field hospital. Patient 1 presented a ballistic trauma of the elbow with a section of the humeral artery (Gustillo IIIC). A TVS was set up during the external fixation of the elbow. Final revascularization was carried out and aponevrotomies of the forearm were performed. Patient 2 had a riddled knee with an open fracture of the femur, an avulsion of the popliteal artery, and a hemorrhagic shock. A strategy of damage control surgery was carried out with placing an arterial and venous shunt. Aponevrotomies of the leg were carried out before casting. For the traumatisms of the arteries of the members, the use of shunts is reserved for the lesions of the proximal vessels. Many vascular shunts available have the same performances to restore the arterial flow and prevent secondary thrombosis. The time before the final revascularization depends on the clinical condition of the patient. The value of anticoagulation in these cases was not shown. PMID- 26362620 TI - A Review of the Potential Local Mechanisms by Which Exercise Improves Functional Outcomes in Intermittent Claudication. AB - BACKGROUND: Intermittent claudication (IC) is a common condition which is associated with significant quality of life limitation. National Institute for Health and Care Excellence guidelines recommend a group-based supervised exercise program as the primary treatment option for claudication, based on clinical and cost effectiveness. This review aims to assess the mechanisms by which exercise improves outcomes in patients with IC. METHODS: MEDLINE, EMBASE, and PubMed were searched using the search strategy "claudication" [AND] "exercise" [AND] "mechanisms." Searches were limited from 1947 to October 2014. Only full-text articles published in the English language in adults (over 18 years of age) were eligible for the review. Any trial involving a nonsupervised exercise program was excluded. Abstracts identified by the database search were interrogated for relevance and citations from the shortlisted papers were hand searched for relevant references. RESULTS: The search yielded a total of 112 studies, of which 42 were duplicates. Forty-seven of the remaining 70 were deemed appropriate for inclusion in the review. Exercise is the first-line treatment for IC. Supervised exercise programs improve walking distances, endothelial and mitochondrial function, muscle strength, and endurance. Furthermore, it leads to a generalized improvement in cardiovascular fitness and overall quality of life. CONCLUSIONS: The mechanism by which exercise improves outcome in claudicants is complicated and multifactorial. Further research is required in this area to fully elucidate the precise and predominant mechanisms and to assess whether targeted exercise program modification maximizes mechanism efficacy and patient outcome. PMID- 26362621 TI - Staged Hybrid Repair of an Intrathoracic Subclavian Artery Aneurysm Associated with a Long Segment Dissection. AB - Intrathoracic subclavian artery aneurysms (ISAAs) are infrequently seen in clinical practice. We report the repair of a left ISAA associated with a long segment dissection from the ostia extending to the axillary artery. A hybrid approach was used. Carotid-to-axillary bypass using a reversed greater saphenous vein was first performed, followed by coverage of the origin of the subclavian artery using a thoracic stent graft. Finally, percutaneous access of the radial artery with coil embolization was performed to successfully thrombose the ISAA. PMID- 26362622 TI - Intraoperative veno-venous extracorporeal lung support in thoracic surgery: a single-centre experience. AB - OBJECTIVES: Intraoperative extracorporeal lung support (ECLS) during thoracic surgical procedures is a modern concept that is gaining increasing acceptance. So far, cardiopulmonary bypass (CPB), veno-arterial extracorporeal membrane oxygenation (v-a-ECMO) or pumpless arterio-venous interventional lung assist (iLA) were utilized for intraoperative support. Only a few case reports have described the use of veno-venous ECMO for intraoperative ECLS. Here, we report our experience with intraoperative ECLS using different veno-venous low-flow and high-flow settings adapted to the individual patient requirements. METHODS: Between April 2014 and April 2015, 9 patients underwent pulmonary resections under ECLS. In 6 patients, a twin-port double-lumen cannula was inserted percutaneously into the right femoral vein for low-flow ECLS. In 3 patients, high flow ECLS was achieved either by femoro-atrial (n = 1) or femoro-jugular cannulation. RESULTS: Indications for ECLS were severely impaired lung function (n = 3), previous pulmonary resections including contralateral pneumonectomy (n = 4), previous single-lung transplantation (sLTX) (n = 1) and extended carinal pneumonectomy (n = 1). Procedures included segmentectomy (n = 3), extended lobectomy with bronchial and vascular anastomoses (n = 1), VATS lobectomy (n = 2), extended left-sided carinal pneumonectomy (n = 1) as well as extended metastasectomy (n = 2). Low-flow ECLS allowed for apnoea up to 45 min in patients with previous pneumonectomy (n = 3) and facilitated protective single-lung ventilation in patients (n = 3) with severely impaired pulmonary function. During trans-sternal carinal pneumonectomy (n = 1), high-flow ECLS achieved by femoro atrial cannulation allowed for apnoea for 40 min, avoiding cross-field ventilation. In 2 patients requiring extended metastasectomy after previous lobectomy of the contralateral lower lobe (n = 1) or pulmonary metastases in the graft after sLTX for end-stage fibrosis (n = 1), high-flow ECLS by percutaneous femoro-jugular cannulation allowed for extensive metastasectomy under optimal atelectasis of the lung. CONCLUSIONS: For intraoperative ECLS, different modes may be applied depending on the intended procedures and required mechanical ventilation. In our experience, different settings of veno-venous ECLS provide sufficient partial or complete lung support, avoiding possible complications associated with other forms of extracorporeal support such as CPB or v-a-ECMO. PMID- 26362623 TI - Impact of the total pericardial closure using bilateral trap door incision and pericardial cavity intervention on outcomes following coronary artery bypass grafting: a randomized, controlled, parallel-group prospective study. AB - OBJECTIVES: In this randomized, controlled and parallel-group prospective study, the feasibility of total pericardial closure with an intrapericardial drain and a pericardio-pleural window (pericardial cavity intervention) was investigated by examining postoperative outcomes, including atrial fibrillation and pericardial effusion, following coronary artery surgery. METHODS: Cases were classified into two groups using a random procedure: the closure group and the open group. Insertion of an intrapericardial drain along the right atrium, pericardio-pleural window and total closure of the pericardium were performed in patients in the closure group. Partial closure of the pericardium was performed in patients in the open group. A straight semi-rigid drain was inserted into the extrapericardial anterior mediastinum and a right angle drain was inserted into the left chest in all patients. The primary endpoint was to evaluate the impact of surgical technique on the rate of postoperative in-hospital atrial fibrillation in the closure group. The secondary endpoint was to evaluate the relationship between the surgical technique and postoperative amount of pericardial effusion. RESULTS: A total of 142 isolated, on-pump cases were examined: 72 in the open group and 70 in the closure group. Postoperative atrial fibrillation occurred in 27.78% of the cases in the open group and 8.57% of the patients in the closure group (P = 0.003). Another statistically significant outcome was the lower incidence of small pericardial effusion in the patient group with a closed pericardium during the second day of postoperative care (P = 0.039). The length of both critical care unit (P = 0.008) and hospital stay (P = 0.047) were also significantly shorter in the patient group with a closed pericardium. CONCLUSIONS: Total pericardiorrhaphy with pericardial cavity intervention can be acceptable and favourable in terms of its outcomes, including reducing incidence of postoperative atrial fibrillation, pericardial effusion and length of hospitalization. PMID- 26362624 TI - High-risk patients and postoperative complications following video-assisted thoracic surgery lobectomy: a case-matched comparison with lower-risk counterparts?. AB - OBJECTIVES: To assess the postoperative incidence of major complications in high risk patients following video-assisted thoracoscopic surgery (VATS) lobectomy for lung cancer compared with their lower risk counterparts. METHODS: A retrospective analysis on prospectively collected data of 348 consecutive patients subjected to VATS lobectomy (August 2012-September 2014) was performed. Patients were defined as high risk if one or more of the following characteristics were present: age >75 years, forced expiratory volume in 1 s (FEV1) <50%, carbon monoxide lung diffusion capacity (DLCO) <50%, history of coronary artery disease (CAD). Severity of complications was graded using the Thoracic Morbidity and Mortality (TM&M) score; major complications were defined if the TM&M score was greater than 2. The propensity score was used to match high-risk patients with their lower risk counterparts in order to minimize the influence of other confounders on outcome. The following variables were used to construct the propensity score: gender, side of operation, body mass index, American Society of Anaesthesiologists score, Eastern Cooperative Oncology Group score, Charlson's Comorbidity Index, number of functioning segments resected. RESULTS: The high risk group consisted of 141 patients (age >75 years: 84 patients; FEV1 <50: 14 patients; DLCO <50: 25 patients; history of CAD: 37 patients). The propensity score yielded two groups of 135 patients (high-risk vs low-risk) well matched for several baseline characteristics except for a lower performance status in the higher-risk group. Compared with their low-risk counterparts, high-risk patients had a higher incidence of cardiopulmonary complications (28 cases, 21% vs 14 cases, 10%; P < 0.0001) and major cardiopulmonary complications (12 cases, 9% vs 3 cases, 2%; P < 0.0001). Postoperative stay was 3 days longer in high-risk patients (8.6 vs 5.5 days, P = 0.0031). The 30-day or in-hospital mortality rates were not different between the two groups (2 cases, 1.5% vs 3 cases, 2.2%, P = 0.93). CONCLUSIONS: The incidence of major complications after VATS lobectomy in high-risk patients is low, but not negligible. This information can be used when discussing surgical risk with the patient during preoperative counselling. PMID- 26362625 TI - Long-term outcomes after surgical ablation for atrial fibrillation in patients with continuous heart rhythm monitoring devices. AB - OBJECTIVES: Surgical ablation for atrial fibrillation (AF) is an established therapy for the treatment of concomitant AF in cardiac surgery patients. We aim to present our prospective experience with 99 continuously monitored patients and investigate whether enhanced monitoring can identify patterns and factors influencing AF recurrence after surgical AF ablation. METHODS: Ninety-nine patients (73 males; age: 68.0 +/- 9.2 years) with documented preoperative AF (paroxysmal: 29; persistent: 18; long-lasting persistent: 52, mean preoperative duration: 46 +/- 53 months) underwent concomitant biatrial surgical ablation (Cox Maze III: 29), full set left atrial cryoablation (n = 22), high-intensity focused ultrasound (HIFU) box lesion (n = 46) or right-sided ablation (n = 2). Postoperative rhythm disclosure was provided via an implantable device. Scheduled follow-up was performed quarterly (mean +/- standard deviation: 1.75 +/- 1.16 years, 173.7 patient-years). RESULTS: The mean postoperative AF burden during the follow-up was 7 +/- 19% (median: 0.2%). Seventy-one and 82 patients had AF burden <1% and <5%, respectively. The preoperative AF duration, preoperative ejection fraction, mitral valve surgery and HIFU in patients with more persistent AF were associated with statistically significant higher postoperative AF burdens. The pattern of AF recurrence during the 3-month blanking period was associated with the amount of later AF recurrence. CONCLUSIONS: Continuous rhythm disclosure reveals that very small amounts of AF burden after surgical ablation are common. The preoperative duration of AF and the use of a box lesion only in patients with longer AF persistence history were independently associated with higher postoperative AF burden recurrence. The temporal AF pattern during the blanking period after ablation should be considered for further patient management and might serve as a prognostic factor. PMID- 26362626 TI - Common arterial trunk: current implementation of the primary and staged repair strategies. AB - OBJECTIVES: In this study, we report our experience on the primary and staged surgical approaches for common arterial trunk (CAT) repair. METHODS: Between August 2003 and February 2015, 16 consecutive patients underwent CAT repair in our institution. Two different approaches have been followed: group 'primary repair' (PR) consists of patients suitable for straightforward CAT repair, who underwent surgery electively at 1-3 months of age (n = 13); group 'staged repair' (SR) consists of critically ill neonates with CAT and poor preoperative status or coexisting interrupted aortic arch (n = 3). They underwent staged CAT repair with aortic arch repair and right ventricular-to-pulmonary artery (RV-PA) shunt within the neonatal period, followed by an intracardiac repair later in infancy. RESULTS: Median age at initial surgical treatment was 8 days (range: 7-21 days) in group SR and 34 days (range: 14-91 days) in group PR (P = 0.03). Mean Aristotle Comprehensive Complexity score was 11 +/- 0.6 (range: 11-13) in group PR and 18 +/- 3.1 (range: 15-21) in group SR (P < 0.01). Follow-up was completed with a median duration of 3.6 years (range: 8 months to 11 years). There was neither early nor late mortality in both groups. In group SR, the median interval to second stage surgery was 216 days (range: 216-260 days). Seven patients (54%) in group PR required reoperation for RV-PA conduit failure (n = 4), truncal valve repair/replacement (n = 2) or both (n = 1). After initial surgery, Kaplan-Meier freedom from reoperation after 1, 2 and 8 years was 77 +/- 12, 68 +/- 13 and 20 +/- 17% in group PR, and 0% in group SR (log-rank P < 0.01). Although all patients in group SR required reoperation to complete the anatomical correction (second stage procedure), there was no surgical reintervention of truncal valve and aortic arch thereafter. CONCLUSIONS: Routine elective CAT repair could be safely performed at 1-3 months of age. However, neonatal CAT repair could be associated with a higher mortality especially in the presence of an interrupted aortic arch. In such cases, a staged CAT repair seems to be associated with favourable postoperative course and improved hospital survival, despite the inevitable need for reoperation, which can be performed at a relatively low risk. PMID- 26362627 TI - Successful hybrid treatment for huge visceral artery aneurysms with contained rupture complicating segmental arterial mediolysis. AB - Segmental arterial mediolysis (SAM) is a rare arteriopathy that can cause acute abdomen. This report describes the case of a 31-year old male suffering from huge visceral aneurysms with contained rupture. We established a treatment strategy using a hybrid procedure that consisted of endovascular and surgical techniques for these splenic, common hepatic artery and coeliac axis aneurysms related to SAM. The patient was successfully treated with aorto-superior mesenteric artery bypass followed by endovascular aortic stent grafting to interrupt inflow to coeliac aneurysms, and distal splenopancreatectomy with en bloc resection of those aneurysms. We conclude that this hybrid procedure consisting of endovascular and surgical techniques is useful and is a safe treatment option for SAM-related visceral aneurysms. PMID- 26362628 TI - Repair of a simple total anomalous pulmonary venous connection coexisting with a persistent left superior vena cava. AB - A simple total anomalous pulmonary venous connection (TAPVC) coexisting with a persistent left superior vena cava (PLSVC) is extremely rare. Connection of the PLSVC with the coronary sinus behind the left atrium induces coronary sinus dilatation. This reduces the free posterior wall space to which the common pulmonary vein is anastomosed for repairing the anomalous connection. Postoperative recurrent pulmonary venous obstruction (PVO) is the most important complication. To prevent PVO, sufficient tension-free anastomosis is necessary. When dilated, the coronary sinus becomes an obstacle for obtaining sufficient incision length in the left atrial cavity. We encountered two cases of a simple TAPVC with a PLSVC in infants weighing 1.8 and 2.9 kg, respectively. To obtain sufficient incision length, we extended the incision line to the right atrium for an atypical supracardiac TAPVC and incised from the left atrium to the coronary sinus via the right atrium for an infracardiac TAPVC. Moreover, we recreated the atrial septum with a rightward shift using a tanned pericardium in both cases. The postoperative courses were uneventful, without recurrent PVO. PMID- 26362629 TI - Is low serum albumin associated with postoperative complications in patients undergoing cardiac surgery? AB - A best evidence topic was written according to a structured protocol. The clinical question investigated was: is low serum albumin associated with postoperative complications in patients undergoing cardiac surgery? There were 62 papers retrieved using the reported search strategy. Of these, 12 publications embodied the best evidence to answer this clinical question. The authors, journal, date and country of the publication, patient group investigated, study design, relevant outcomes and results of these papers were tabulated. This paper includes a total of 12 589 patients, and of the papers reviewed, 4 were level 3 and 8 level 4. Each of the publications reviewed and compared either all or some of the following postoperative complications: mortality, postoperative bleeding requiring reoperation, prolonged hospital stay and ventilatory support, infection, liver dysfunction, delirium and acute kidney injury (AKI). Of the studies that examined postoperative mortality, all except for three established a significant multivariate association with low preoperative albumin level. Some scepticism is required in accepting other results that were only present in univariate analysis. While three studies examined multiple levels of serum albumin, most dichotomized the serum albumin levels into normal and abnormal groups. This led to differing classifications of hypoalbuminaemia, ranging from less than 2.5 to 4.0 g/dl. The available evidence, however, suggests that low preoperative serum albumin level in patients undergoing cardiac surgery is associated with the following: (i) increased risk of mortality after surgery and (ii) greater incidence of postoperative morbidity. While the evidence supports the use of preoperative albumin in assessing post-cardiac surgery complications, a specific level of albumin considered to be abnormal cannot be concluded from this review. PMID- 26362630 TI - Cardiovascular Magnetic Resonance Visualization of Cardiac Amyloid Infiltration: Challenges and Opportunities. PMID- 26362631 TI - Prognostic Value of Late Gadolinium Enhancement Cardiovascular Magnetic Resonance in Cardiac Amyloidosis. AB - BACKGROUND: The prognosis and treatment of the 2 main types of cardiac amyloidosis, immunoglobulin light chain (AL) and transthyretin (ATTR) amyloidosis, are substantially influenced by cardiac involvement. Cardiovascular magnetic resonance with late gadolinium enhancement (LGE) is a reference standard for the diagnosis of cardiac amyloidosis, but its potential for stratifying risk is unknown. METHODS AND RESULTS: Two hundred fifty prospectively recruited subjects, 122 patients with ATTR amyloid, 9 asymptomatic mutation carriers, and 119 patients with AL amyloidosis, underwent LGE cardiovascular magnetic resonance. Subjects were followed up for a mean of 24+/-13 months. LGE was performed with phase-sensitive inversion recovery (PSIR) and without (magnitude only). These were compared with extracellular volume measured with T1 mapping. PSIR was superior to magnitude-only inversion recovery LGE because PSIR always nulled the tissue (blood or myocardium) with the longest T1 (least gadolinium). LGE was classified into 3 patterns: none, subendocardial, and transmural, which were associated with increasing amyloid burden as defined by extracellular volume (P<0.0001), with transitions from none to subendocardial LGE at an extracellular volume of 0.40 to 0.43 (AL) and 0.39 to 0.40 (ATTR) and to transmural at 0.48 to 0.55 (AL) and 0.47 to 0.59 (ATTR). Sixty-seven patients (27%) died. Transmural LGE predicted death (hazard ratio, 5.4; 95% confidence interval, 2.1-13.7; P<0.0001) and remained independent after adjustment for N-terminal pro-brain natriuretic peptide, ejection fraction, stroke volume index, E/E', and left ventricular mass index (hazard ratio, 4.1; 95% confidence interval, 1.3-13.1; P<0.05). CONCLUSIONS: There is a continuum of cardiac involvement in systemic AL and ATTR amyloidosis. Transmural LGE is determined reliably by PSIR and represents advanced cardiac amyloidosis. The PSIR technique provides incremental information on outcome even after adjustment for known prognostic factors. PMID- 26362632 TI - The Contemporary Safety and Effectiveness of Lower Extremity Bypass Surgery and Peripheral Endovascular Interventions in the Treatment of Symptomatic Peripheral Arterial Disease. AB - BACKGROUND: Treatment for symptomatic peripheral artery disease includes lower extremity bypass surgery (LEB) and peripheral endovascular interventions (PVIs); however, limited comparative effectiveness data exist between the 2 therapies. We assessed the safety and effectiveness of LEB and PVI in patients with symptomatic claudication and critical limb ischemia. METHODS AND RESULTS: In a community based clinical registry at 2 large integrated healthcare delivery systems, we compared 883 patients undergoing PVI and 975 patients undergoing LEB between January 1, 2005 and December 31, 2011. Rates of target lesion revascularization were greater for PVI than for LEB in patients presenting with claudication (12.3+/-2.7% and 19.0+/-3.5% at 1 and 3 years versus 5.2+/-2.4% and 8.3+/-3.1%, log-rank P<0.001) and critical limb ischemia (19.1+/-4.8% and 31.6+/-6.3% at 1 and 3 years versus 10.8+/-2.5% and 16.0+/-3.2%, log-rank P<0.001). However, in comparison with PVI, LEB was associated with increased rates of complications up to 30 days following the procedure (37.1% versus 11.9%, P<0.001). There were no differences in amputation rates between the 2 groups. Findings remained consistent in sensitivity analyses by using propensity methods to account for treatment selection. CONCLUSIONS: In patients with symptomatic peripheral artery disease, in comparison with LEB, PVI was associated with fewer 30-day procedural complications, higher revascularization rates at 1 and 3 years, and no difference in subsequent amputations. PMID- 26362633 TI - Adipocyte-Derived Hormone Leptin Is a Direct Regulator of Aldosterone Secretion, Which Promotes Endothelial Dysfunction and Cardiac Fibrosis. AB - BACKGROUND: In obesity, the excessive synthesis of aldosterone contributes to the development and progression of metabolic and cardiovascular dysfunctions. Obesity induced hyperaldosteronism is independent of the known regulators of aldosterone secretion, but reliant on unidentified adipocyte-derived factors. We hypothesized that the adipokine leptin is a direct regulator of aldosterone synthase (CYP11B2) expression and aldosterone release and promotes cardiovascular dysfunction via aldosterone-dependent mechanisms. METHODS AND RESULTS: Immunostaining of human adrenal cross-sections and adrenocortical cells revealed that adrenocortical cells coexpress CYP11B2 and leptin receptors. Measurements of adrenal CYP11B2 expression and plasma aldosterone levels showed that increases in endogenous (obesity) or exogenous (infusion) leptin dose-dependently raised CYP11B2 expression and aldosterone without elevating plasma angiotensin II, potassium or corticosterone. Neither angiotensin II receptors blockade nor alpha and beta adrenergic receptors inhibition blunted leptin-induced aldosterone secretion. Identical results were obtained in cultured adrenocortical cells. Enhanced leptin signaling elevated CYP11B2 expression and plasma aldosterone, whereas deficiency in leptin or leptin receptors blunted obesity-induced increases in CYP11B2 and aldosterone, ruling out a role for obesity per se. Leptin increased intracellular calcium, elevated calmodulin and calmodulin-kinase II expression, whereas calcium chelation blunted leptin-mediated increases in CYP11B2, in adrenocortical cells. Mineralocorticoid receptor blockade blunted leptin-induced endothelial dysfunction and increases in cardiac fibrotic markers. CONCLUSIONS: Leptin is a newly described regulator of aldosterone synthesis that acts directly on adrenal glomerulosa cells to increase CYP11B2 expression and enhance aldosterone production via calcium-dependent mechanisms. Furthermore, leptin-mediated aldosterone secretion contributes to cardiovascular disease by promoting endothelial dysfunction and the expression of profibrotic markers in the heart. PMID- 26362635 TI - Arrhythmia Protection in Hypokalemia: A Novel Role of Ca2+-Activated K+ Currents in the Ventricle. PMID- 26362634 TI - Small-Conductance Calcium-Activated Potassium Current Is Activated During Hypokalemia and Masks Short-Term Cardiac Memory Induced by Ventricular Pacing. AB - BACKGROUND: Hypokalemia increases the vulnerability to ventricular fibrillation. We hypothesize that the apamin-sensitive small-conductance calcium-activated potassium current (IKAS) is activated during hypokalemia and that IKAS blockade is proarrhythmic. METHODS AND RESULTS: Optical mapping was performed in 23 Langendorff-perfused rabbit ventricles with atrioventricular block and either right or left ventricular pacing during normokalemia or hypokalemia. Apamin prolonged the action potential duration (APD) measured to 80% repolarization (APD80) by 26 milliseconds (95% confidence interval [CI], 14-37) during normokalemia and by 54 milliseconds (95% CI, 40-68) during hypokalemia (P=0.01) at a 1000-millisecond pacing cycle length. In hypokalemic ventricles, apamin increased the maximal slope of APD restitution, the pacing cycle length threshold of APD alternans, the pacing cycle length for wave-break induction, and the area of spatially discordant APD alternans. Apamin significantly facilitated the induction of sustained ventricular fibrillation (from 3 of 9 hearts to 9 of 9 hearts; P=0.009). Short-term cardiac memory was assessed by the slope of APD80 versus activation time. The slope increased from 0.01 (95% CI, -0.09 to 0.12) at baseline to 0.34 (95% CI, 0.23-0.44) after apamin (P<0.001) during right ventricular pacing and from 0.07 (95% CI, -0.05 to 0.20) to 0.54 (95% CI, 0.06 1.03) after apamin infusion (P=0.045) during left ventricular pacing. Patch-clamp studies confirmed increased IKAS in isolated rabbit ventricular myocytes during hypokalemia (P=0.038). CONCLUSIONS: Hypokalemia activates IKAS to shorten APD and maintain repolarization reserve at late activation sites during ventricular pacing. IKAS blockade prominently lengthens the APD at late activation sites and facilitates ventricular fibrillation induction. PMID- 26362636 TI - Subchronic exposure to leachate activates key markers linked with neurological disorder in Wistar male rat. AB - The linking of various environmental chemicals exposure to neurodegenerative disorders is current. This study was undertaken to elucidate the toxic effects and the underlying biochemical mechanism of leachate obtained from Elewi Odo municipal battery recycling site (EOMABRL) using key markers of neuronal damage in rat via an oral route. Analysis of the concentrations of heavy metals showed that lead, cadmium, nickel, chromium, manganese, and iron were higher than the acceptable limits set by the regulatory authority-the World Health Organization. Whereas, copper, zinc, and cobalt were lower than permissible limits. EOMABRL was administered at 0, 20, 40, 60, 80, and 100% concentrations to adult male rats for 60 days. An in vitro study was also carried out in the cerebellum to assess cholinesterase biochemistry assays. Following exposure, brain was collected to determine the antioxidant status. EOMABRL administration significantly increased superoxide dismutase (SOD) and catalase (CAT) activities, and a sequential decrease in reduced glutathione (GSH) level with a concomitant increase in the accumulation of hydrogen peroxide (H2O2) and malondialdehyde (MDA) level was observed, when compared with the control. The treated rat had a significant (P < 0.05) increase in the activities of acetycholinesterase (AChE) and butyrylcholinesterase (BuChE). Taken together, these findings conclude that some possible mechanisms by which EOMABRL elicits neuronal disorder in male rat could be through the activation of AChE and BuChE and induction of oxidative stress with necrosis of neuronal cells. PMID- 26362637 TI - Evidence for anaerobic ammonium oxidation process in freshwater sediments of aquaculture ponds. AB - The anaerobic ammonium oxidation (anammox) process, which can simultaneously remove ammonium and nitrite, both toxic to aquatic animals, can be very important to the aquaculture industry. Here, the presence and activity of anammox bacteria in the sediments of four different freshwater aquaculture ponds were investigated by using Illumina-based 16S rRNA gene sequencing, quantitative PCR assays and (15)N stable isotope measurements. Different genera of anammox bacteria were detected in the examined pond sediments, including Candidatus Brocadia, Candidatus Kuenenia and Candidatus Anammoxoglobus, with Candidatus Brocadia being the dominant anammox genus. Quantitative PCR of hydrazine synthase genes showed that the abundance of anammox bacteria ranged from 5.6 * 10(4) to 2.1 * 10(5) copies g(-1) sediment in the examined ponds. The potential anammox rates ranged between 3.7 and 19.4 nmol N2 g(-1) sediment day(-1), and the potential denitrification rates varied from 107.1 to 300.3 nmol N2 g(-1) sediment day(-1). The anammox process contributed 1.2-15.3% to sediment dinitrogen gas production, while the remainder would be due to denitrification. It is estimated that a total loss of 2.1-10.9 g N m(-2) per year could be attributed to the anammox process in the examined ponds, suggesting that this process could contribute to nitrogen removal in freshwater aquaculture ponds. PMID- 26362638 TI - Oxidative stress responses and toxin accumulation in the freshwater snail Radix swinhoei (Gastropoda, Pulmonata) exposed to microcystin-LR. AB - Microcystin-LR (MCLR) is one of the most common toxins in eutrophic freshwater ecosystems. The ecotoxicological effects of MCLR in freshwater ecosystems have been widely documented; however, the physiological effects of MCLR on freshwater snails and the underlying toxicity/detoxification mechanisms have not been well investigated. In this laboratory study, antioxidant system responses in the hepatopancreas and the digestive tract of Radix swinhoei, a typical freshwater snail, exposed to 0.01 mg/L to 2 mg/L MCLR were explored. Antioxidant enzymes, particularly superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD), in the digestive tracts were effectively generated at 0.2 and 2 mg/L MCLR. However, SOD and CAT activities in the hepatopancreas were activated only at 0.2 mg/L MCLR. Glutathione (GSH) concentrations in the digestive tracts significantly increased at 0.01 to 0.2 mg/L MCLR; by comparison, GSH concentrations in the hepatopancreas remained stable. No oxidative damage (lipid peroxidations) occurred in the digestive tracts and the hepatopancreas when the snail was exposed to <=0.2 mg/L MCLR. MCLR accumulation in different snail tissues was also examined. MCLR accumulated in different tissues and showed the following pattern: hepatopancreas > gonads > digestive tracts > muscles. Bioaccumulated concentrations in these four tissues increased as MCLR exposure concentrations increased; by contrast, bioaccumulation factors decreased as MCLR exposure concentrations increased. Our results indicated that R. swinhoei is sensitively responsive to MCLR by changing antioxidant system status to cope with the toxicity. Snails may be vectors of MCs that transfer MCs in eutrophic lakes via food chains or food web. PMID- 26362639 TI - Effectiveness of bulking agents for co-composting penicillin mycelial dreg (PMD) and sewage sludge in pilot-scale system. AB - Penicillin mycelial dreg (PMD) has a distinguishing characteristic of the high content of penicillin residue and nutrients. The existing handling of PMD used as feed additive of livestock and poultry is facing a direct challenge of penicillin transportation into environment due to the inadequate absorption through the digestive system. This work aims at examining the feasibility of co-composting of PMD with sewage sludge (SWS) in a pilot-scale system and evaluating the effect of four bulking agents. Seven treatments were co-composted over a 32-day period in 390-L reactors using the same PMD and SWS with different bulking agents, corresponding to the seven formulas (T-1: PMD + SWS + RS; T-2: PMD + SWS + WS; T 3: PMD + SWS + RS + SD; T-4: PMD + SWS + WS + SD; T-5: PMD + SWS + SD; T-6: PMD + SWS + RS + WS; control: PMD + SWS). The parameters monitored over this period included temperature, organic matter (OM), TN, NH4(+)-N, NO3(-)-N, pH, EC, penicillin residue, as well as germination index (GI). The results showed that co composting PMD and SWS with BA is feasible. The highest rate of OM mineralization was observed in T-3, while below 30% for T-2, T-4, and T-5. Furthermore, the SD addition resulted in both the increase in the duration of thermophilic stage and maximum temperature and the decrease in TN losses, particularly in T-3, suggesting that the formula of the T-3 is very suitable option for the co composting of PMD and SWS. PMID- 26362640 TI - A review of soil cadmium contamination in China including a health risk assessment. AB - Cadmium (Cd) is one of the most serious soil contaminants in China, and it poses an increasing risk to human health as large amounts of Cd are emitted into the environment. However, knowledge about soil Cd concentrations and the human health risks of these concentrations at a national scale is limited. In this study, we conducted a review of 190 articles about soil Cd concentrations during 2001 to 2010. The study involved 146 cities in China, and we quantified the risks to human health according to different regions. The results showed that elevated Cd levels were present compared to the background value of soil in 1990, and the soil Cd concentrations in the Guangxi province exceeded even the class III Soil Environmental Quality standard, which is the limit for the normal growth of plants. The Chinese soil Cd concentrations ranged from 0.003 mg kg(-1) to 9.57 mg kg(-1). The soil Cd concentrations had the following trend: northwest > southwest > south central > east > northeast > north. The sources of soil Cd are mainly from smelting, mining, waste disposal, fertilizer and pesticide application, and vehicle exhaust, etc. but differentiated in various regions. The soil Cd contamination in urban areas was more serious than contamination in the agricultural areas. Currently, there is no significant non-carcinogenic risk in any of the provinces. Regarding the different exposure pathways, the dermal pathway is the primary source of soil Cd exposure, and the risk associated with this pathway is generally hundreds of times higher than the risk for an ingestion pathway. For most of the provinces, the health risk to the urban population was higher than the risk to the rural population. For each population, the carcinogenic risk was less than 10(-6) in most of the provinces, except for the urban population in the Hunan province. If the other exposure pathways are fully considered, then the people in these areas may have a higher carcinogenic risk. This review provides a comprehensive assessment of soil Cd pollution in China, and it identifies policy recommendations for pollution mitigation and environmental management in the relevant regions. PMID- 26362641 TI - Effect of thermal pre-treatment on the availability of PAHs for successive chemical oxidation in contaminated soils. AB - This is the premier study designed to evaluate the impact of thermal pre treatment on the availability of polycyclic aromatic hydrocarbons (PAHs) for successive removal by chemical oxidation. Experiments were conducted in two soils having different PAH distribution originating from former coking plant sites (Homecourt, H, and Neuves Maisons, NM) located in northeast of France. Soil samples were pre-heated at 60, 100, and 150 degrees C for 1 week under inert atmosphere (N2). Pre-heating resulted in slight removal of PAHs (<10%) and loss of extractable organic matter (EOM). Then, these pre-heated soil samples were subjected to Fenton-like oxidation (H2O2 and magnetite) at room temperature. Chemical oxidation in soil without any pre-treatment showed almost no PAH degradation underscoring the unavailability of PAHs. However, chemical oxidation in pre-heated soils showed significant PAH degradation (19, 29, and 43% in NM soil and 31, 36, and 47% in H soil pre-treated at 60, 100, and 150 degrees C, respectively). No preferential removal of PAHs was observed after chemical oxidation in both soils. These results indicated the significant impact of pre heating temperature on the availability of PAHs in contaminated soils and therefore may have strong implications in the remediation of contaminated soils especially where pollutant availability is a limiting factor. PMID- 26362643 TI - Editorial: Contemporary siRNA Therapeutics and the Current State-of-Art. PMID- 26362642 TI - Arsenic release from the abiotic oxidation of arsenopyrite under the impact of waterborne H2O2: a SEM and XPS study. AB - Our previous study has proven that waterborne hydrogen peroxide can affect the arsenic releasing process from arsenopyrite powder, but little is known about the change of morphology and element constitutes on arsenopyrite surface. In this study, a simulated experiment was conducted to examine the effects of hydrogen peroxide (at a concentration range of 5-50 MUM) on the abiotic oxidation of arsenopyrite cubes. Scanning electron microscopy (SEM), energy dispersive X-ray spectrometer (EDS), and X-ray photoelectron spectroscopy (XPS) were used to characterize the changes of microstructure morphology and elemental species on arsenopyrite surface. The results showed that micromolar level of H2O2 accelerated the release of arsenic and iron but passivated the sulfur release from arsenopyrite surfaces. As(III) oxidation in solution was enhanced at the early part of the experiment, but the release of As(III) was facilitated at the latter part. As(V) concentrations in solution increased along with the elevated H2O2 dosage level. The SEM images showed different surface microstructure on the surface of CK and all the treatments. EDS results showed that the ratios of S/Fe, Fe/As, and S/As in bulk arsenopyrite revealed evident increasing trend along with the increase of H2O2 dosage level. As the result of surface leaching, the XPS results did not show significant trend, while it suggests that H2O2 accelerated the formation of Fe-As oxidized layer on the arsenopyrite surface. PMID- 26362644 TI - Progress in Topical siRNA Delivery Approaches for Skin Disorders. AB - The topical application of therapeutic agent has shown promising efficacy in the treatment of skin disorders. The siRNA based therapies have been used for treatment of various disorders including skin diseases. The topical delivery of siRNA based therapies has opened new perspectives for the treatment of skin disorders. The use of siRNA is limited due to the rapid degradation and poor cellular uptake. Also, the stratum corneum, the top layer of skin is the major barrier for the delivery of topical agents. There is unmet need for efficient topical formulation that will deliver the siRNA to the site of action and also overcome the associated siRNA delivery limitations. The topical delivery of siRNA has been achieved using viral or nonviral methods, and the combination of non viral methods with an active permeation method such as iontophoresis, sonophoresis or microneedles for the treatment of skin disorders. These delivery approaches have been tested in a preclinical setup and few cases the results have shown promise for clinical trials. This review provides an update on the advances in the non-viral delivery approaches for siRNA delivery for skin disorders and use of various delivery approaches for efficient delivery at the disease site. PMID- 26362645 TI - Pygidiopsis cambodiensis n. sp. (Digenea: Heterophyidae) from experimental hamsters infected with metacercariae in mullets from Cambodia. AB - Pygidiopsis cambodiensis n. sp. is described based on adult flukes recovered from Syrian golden hamsters experimentally infected with metacercariae from mullets (Liza macrolepis) purchased at a local fish market in Phnom Penh, Cambodia. The specimens were examined by light and scanning electron microscopy. Among the 13 species so far assigned to Pygidiopsis, the new species belongs to the summa-type (including Pygidiopsis pelecani, Pygidiopsis phalacrocoracis, Pygidiopsis piclaumoreli, Pygidiopsis plana, and Pygidiopsis summa) which lack circumoral spines and have vitelline follicles extending posteriorly from the level of the ovary some distance into the post-testicular space and the uterus not exceeding the acetabulum anteriorly. The new species differs from the other five species of the summa-type particularly in the morphology of the ventrogenital complex, including the genital sac, gonotyl, and gonotyl spines (= rodlets). The genital sac is well developed, sucker-like, slightly larger than the ventral sucker, muscular, and equipped with two gonotyls on the ventral side of the sac. Gonotyls are protruding pad-like, and the number of rodlets on the left gonotyl is four to five and that on the right gonotyl is 10-11 in two rows. This is the fifth Pygidiopsis species reported in Asia, following P. summa (Japan, Korea, and Vietnam), P. phalacrocorasis (Japan), P. pelecani (China), and Pygidiopsis marivillai (Philippines). PMID- 26362646 TI - Toxoplasma gondii, Dirofilaria immitis, feline immunodeficiency virus (FIV), and feline leukemia virus (FeLV) infections in stray and pet cats (Felis catus) in northwest China: co-infections and risk factors. AB - This study was conducted to estimate the prevalence of Toxoplasma gondii, Dirofilaria immitis, feline immunodeficiency virus (FIV), and feline leukemia virus (FeLV) infections among stray and pet cats in Lanzhou, northwest China, and to identify the influence of age, gender, and regions on seropositivity. T. gondii antibodies were examined in cat sera by the modified agglutination test (MAT). The circulating antigens of D. immitis and FeLV and specific antibodies to FIV were examined using kits commercially available. The overall prevalence of T. gondii, FIV, FeLV, and D. immitis was 19.34, 9.12, 11.33, and 3.04 %, respectively. For the genetic characterization of T. gondii genotypes in cats, genomic DNA was extracted from the seropositive cats and the T. gondii B1 gene was amplified using a semi-nested PCR. DNA samples giving positive B1 amplification were then genotyped using multilocus PCR-RFLP. Two T. gondii genotypes (ToxoDB#9 and ToxoDB#1) were identified. Results of the multivariate logistic regression analysis showed that older cats are more likely to be seropositive than juveniles for T. gondii, FIV, FeLV, and D. immitis. This is the first report of T. gondii genotypes in cats in northwest China. Moreover, the present study is the first study of retrovirus and D. immitis seroprevalence in cats in China. The results revealed that T. gondii, FIV, and FeLV infections are common in stray and pet cats in northwest China. PMID- 26362647 TI - Metaphyseal bone loss in revision knee arthroplasty. AB - The etiology of bone loss encountered during revision total knee arthroplasty (TKA) is often multifactorial and can include stress shielding, osteolysis, osteonecrosis, infection, mechanical loss due to a grossly loose implant, and iatrogenic loss at the time of implant resection. Selection of the reconstructive technique(s) to manage bone deficiency is determined by the location and magnitude of bone loss, ligament integrity, surgeon experience, and patient factors including the potential for additional revision, functional demand, and comorbidities. Smaller, contained defects are reliably managed with bone graft, cement augmented with screw fixation, or modular augments. Large metaphyseal defects require more extensive reconstruction such as impaction bone grafting with or without mesh augmentation, prosthetic augmentation, use of bulk structural allografts, or use of metaphyseal cones or sleeves. While each technique has advantages and disadvantages, the most optimal method for reconstruction of large metaphyseal bone defects during revision TKA is not clearly established. PMID- 26362648 TI - Antidepressant prescribing in Irish children: secular trends and international comparison in the context of a safety warning. AB - BACKGROUND: In 2003, the Irish Medicines Board (IMB) warned against the treatment of childhood depression with selective serotonin reuptake inhibitors (SSRIs) due to increased risk of suicide. This study examined the effect of this warning on the prevalence of anti-depressants in Irish children and compared age and gender trends and international comparisons of prescription rates. METHODS: A retrospective cohort study of the Irish Health Service Executive (HSE) pharmacy claims database for the General Medical Services (GMS) scheme for dispensed medication. Data were obtained for 2002-2011 for those aged <= 15 years. Prevalence of anti-depressants per 1000 eligible population, along with 95% confidence intervals, were calculated. A negative binomial regression analysis was used to investigate trends and compare rates across years, sex and age groups (0-4, 5-11, 12-15 years). International prescribing data were retrieved from the literature. RESULTS: The prevalence of anti-depressants decreased from 4.74/1000 population (95% CI: 4.47-5.01) in 2002 to 2.61/1000 population (95% CI: 2.43 2.80) in 2008. SSRI rates decreased from 2002 to 2008. Prescription rates for contra-indicated SSRIs paroxetine, sertraline and citralopram decreased significantly from 2002 to 2005, and, apart from paroxetine, only small fluctuations were seen from 2005 onwards. Fluoxetine was the most frequently prescribed anti-depressant and rates increased between 2002 and 2011. Anti depressant rates were higher for younger boys and older girls. The Irish prevalence was lower than the US, similar to the U.K. and higher than Germany and Denmark. CONCLUSIONS: The direction and timing of these trends suggest that medical practitioners followed the IMB advice. PMID- 26362649 TI - Gene expression meta-analysis reveals immune response convergence on the IFNgamma STAT1-IRF1 axis and adaptive immune resistance mechanisms in lymphoma. AB - BACKGROUND: Cancers adapt to immune-surveillance through evasion. Immune responses against carcinoma and melanoma converge on cytotoxic effectors and IFNgamma-STAT1-IRF1 signalling. Local IFN-driven immune checkpoint expression can mediate feedback inhibition and adaptive immune resistance. Whether such coupled immune polarization and adaptive resistance is generalisable to lymphoid malignancies is incompletely defined. The host response in diffuse large B-cell lymphoma (DLBCL), the commonest aggressive lymphoid malignancy, provides an empirical model. METHODS: Using ten publicly available gene expression data sets encompassing 2030 cases we explore the nature of host response in DLBCL. Starting from the "cell of origin" paradigm for DLBCL classification, we use the consistency of differential expression to define polarized patterns of immune response genes in DLBCL, and derive a linear classifier of immune response gene expression. We validate and extend the results in an approach independent of "cell of origin" classification based on gene expression correlations across all data sets. RESULTS: T-cell and cytotoxic gene expression with polarization along the IFNgamma-STAT1-IRF1 axis provides a defining feature of the immune response in DLBCL. This response is associated with improved outcome, particularly in the germinal centre B-cell subsets of DLBCL. Analysis of gene correlations across all data sets, independent of "cell of origin" class, demonstrates a consistent association with a hierarchy of immune-regulatory gene expression that places IDO1, LAG3 and FGL2 ahead of PD1-ligands CD274 and PDCD1LG2. CONCLUSION: Immune responses in DLBCL converge onto the IFNgamma-STAT1-IRF1 axis and link to diverse potential mediators of adaptive immune resistance identifying future therapeutic targets. PMID- 26362650 TI - Emergence and predominance of norovirus GII.17 in Huzhou, China, 2014-2015. AB - BACKGROUND: Norovirus (NoV) has been recognized as the leading cause of both outbreaks and sporadic cases of acute gastroenteritis in children and adults worldwide. Stool samples collected from outpatients with clinical symptoms of acute gastroenteritis in all age groups at the First People's Hospital in Huzhou, Huzhou, China between March 2014 and February 2015 were analyzed to gain insight into the epidemiology and genetic variation in NoV strains circulating in China. METHOD: Real-time RT-PCR (qPCR) was performed for Norovirus detection. RT-PCR were used for genomic amplification and sequencing. Genogroup and genotype were assigned using the NoV Noronet typing tool and the strains were named according to the time of isolation. The phylogenetic analysis was conducted using MEGA 5. RESULTS: Of the 809 specimens, 193 (23.9 %) were positive for NoV, with GII.4 and GII.17 the most commonly identified strains. Phylogenetic analysis confirmed the presence of five recombinant strains in Huzhou. Recombinants GII.P13/GII.17 and GII.P12/GII.4 were newly detected in China. The GII.P13/GII.17 recombinant was first identified in October 2014 and steadily replaced GII.Pe/GII.4 (GII.4 Sydney 2012) as the predominant circulating NoV genotype. CONCLUSION: This is the first report of the detection of GII.17 in the Huzhou area and of a NoV genotype being detected in greater numbers than GII.4. Furthermore, our results indicated that following the emergence of GII.17 in October 2014, it steadily replaced the previous circulating GII.4 Sydney2012 strain, which was the dominant circulating genotype for the past 2 years. As norovirus are the important cause of nonbacterial gastroenteritis, continuous and comprehensive study of the norovirus strains involved in large and cost-effective acute gastroenteritis would help understanding the molecular epidemiology of norovirus infections and development of improved prevention and control measures. PMID- 26362651 TI - Nuclear heterogeneity in conidial populations of Aspergillus flavus. AB - Aspergillus flavus is a major producer of aflatoxin and an opportunistic pathogen for a wide range of hosts. Understanding genotypic and phenotypic variation within strains of A. flavus is important for controlling disease and reducing aflatoxin contamination. A. flavus is multinucleate and predominantly haploid (n) and homokaryotic. Although cryptic heterokaryosis may occur in nature, it is unclear how nuclei in A. flavus influence genetic heterogeneity and if nuclear condition plays a role in fungal ecology. A. flavus mainly reproduces asexually by producing conidia. In order to observe whether conidia are homokaryotic or heterokaryotic, we labeled nuclei of A. flavus using two different nuclear localized fluorescent reporters. The reporter constructs (pYH2A and pCH2B), encode histones HH2A and HH2B fused at the C terminus with either yellow (EYFP) or cyan (ECFP) fluorescent proteins, respectively. The constructs were transformed into the double auxotrophic strain AFC-1 (-pyrG, -argD) to generate a strain containing each reporter construct. By taking advantage of the nutritional requirement for each strain, we were able to generate fusants between FR36 ( argD) expressing yellow fluorescence, and FR46 (-pyr4) expressing cyan fluorescence. Conidia from fusants between FR36 and FR46 showed three types of fluorescence: only EYFP, only ECFP or both EYFP+ECFP. Conidia containing nuclei expressing EYFP+ECFP were separated by Fluorescence-Activated Cell sorting (FACS) and were found to contain both yellow and cyan fluorescent markers in the same nucleus. Further characterization of conidia having only one nucleus but expressing both EYFP+ECFP fluorescence were found to be diploid (2n). Our findings suggest that A. flavus maintains nuclear heterogeneity in conidial populations. PMID- 26362652 TI - Gene-gene interaction analysis identifies a new genetic risk factor for colorectal cancer. AB - BACKGROUND: Adiponectin levels have been shown to be associated with colorectal cancer (CRC). Furthermore, a newly identified adiponectin receptor, T-cadherin, has been associated with plasma adiponectin levels. Therefore, we investigated the potential for a genetic association between T-cadherin and CRC risk. RESULT: We conducted a case-control study using the Korean Cancer Prevention study-II cohort, which is composed of 325 CRC patients and 977 normal individuals. Study results revealed that rs3865188 in the 5' flanking region of the T-cadherin gene (CDH13) was significantly associated with CRC (p = 0.0474). The odds ratio (OR) for the TT genotype as compared to the TA + AA genotype was 1.577 (p = 0.0144). In addition, the interaction between CDH13 and the adiponectin gene (APN) for CRC risk was investigated using a logistic regression analysis. Among six APN single nucleotide polymorphisms (rs182052, rs17366568, rs2241767, rs3821799, rs3774261, and rs6773957), an interaction with the rs3865188 was found for four (rs2241767, rs3821799, rs3774261, and rs6773957). The group with combined genotypes of TT for rs3865188 and GG for rs377426 displayed the highest risk for CRC development as compared to those with the other genotype combinations. The OR for the TT/GG genotype as compared to the AA/AA genotype was 4.108 (p = 0.004). Furthermore, the plasma adiponectin level showed a correlation with the gene-gene interaction, and the group with the highest risk for CRC had the lowest adiponectin level (median, 4.8 MUg/mL for the TT/GG genotype vs.7.835 MUg/mL for the AA/AA genotype, p = 0.0017). CONCLUSIONS: The present study identified a new genetic factor for CRC risk and an interaction between CDH13 and APN in CRC risk. These genetic factors may be useful for predicting CRC risk. PMID- 26362653 TI - Widespread and Adaptive Alterations in Genome-Wide Gene Expression Associated with Ecological Divergence of Two Oryza Species. AB - Ecological speciation is a common mechanism by which new species arise. Despite great efforts, the role of gene expression in ecological divergence and speciation is poorly understood. Here, we conducted a genome-wide gene expression investigation of two Oryza species that are evolutionarily young and distinct in ecology and morphology. Using digital gene expression technology and the paired end RNA sequencing method, we obtained 21,415 expressed genes across three reproduction-related tissues. Of them, approximately 8% (1,717) differed significantly in expression levels between the two species and these differentially expressed genes are randomly distributed across the genome. Moreover, 62% (1,064) of the differentially expressed genes exhibited a signature of directional selection in at least one species. Importantly, the genes with differential expression between species evolved more rapidly at the 5' flanking sequences than the genes without differential expression relative to coding sequences, suggesting that cis-regulatory changes are likely adaptive and play an important role in the ecological divergence of the two species. Finally, we showed evidence of significant differentiation between species in phenotype traits and observed that genes with differential expression were overrepresented with functional terms involving phenotypic and ecological differentiation between the two species, including reproduction- and stress-related characteristics. Our findings demonstrate that ecological speciation is associated with widespread and adaptive alterations in genome-wide gene expression and provide new insights into the importance of regulatory evolution in ecological speciation in plants. PMID- 26362654 TI - The effect of semaphorin 3A on fracture healing in osteoporotic rats. AB - BACKGROUNDS: Semaphorin 3A (Sema3A) was demonstrated to exert an osteoprotective effect by both inhibiting osteoclastic bone resorption and promoting osteoblastic bone formation. The effect of Sema3A on fracture healing of osteoporotic rats was investigated in this study. METHODS: Twelve weeks after bilateral ovariectomy, all animals underwent unilateral transverse osteotomy on the proximal tibiae, and were then randomly divided into two groups. Rats received vehicle (control) or weekly local injection of Sema3A (500 MUg/kg) into the injury site (group Sema3A) after fracture surgery until sacrifice at 4 and 8 weeks. Specimens were harvested and examined by radiography, iDXA, histology, micro-CT, and three-point bending test. RESULTS: Compared to control, Sema3A treatment significantly increased bone mineral density, percent bone volume and biomechanical strength of the callus at 4 and 8 weeks post-fracture. At 8 weeks after fracture, the bone volume of callus showed no difference between groups, while the average cross-sectional area of callus in the control group was 43.8 % higher than that of Sema3A group. Histological images showed increased callus formation at 4 weeks post-fracture and better callus ossification in the Sema3A group, while callus remodeling in the control group seemed to be delayed and not well bridged. CONCLUSIONS: Results in this study indicated that Sema3A treatment increased callus volume and density at 4 weeks post-fracture, and induced promoted callus ossification and remodeling at 8 weeks post-fracture compared to control. PMID- 26362655 TI - Potential risk of excising the femoral insertion of the popliteus tendon during primary total knee arthroplasty: a biometric study. AB - BACKGROUND: During total knee arthroplasty (TKA), excision of the popliteus tendon leads to extensive static gaps and reduced mobility. The purpose of this study was to determine the positional relationship between the femoral insertion of the popliteus tendon and the bone cutting lines of various TKA systems. METHODS: This study included 21 cadaveric right femurs presenting no macroscopic deformity. The lateral image of the femur and the template of the femoral component were overlaid to determine the preservation/excision of the popliteus tendon insertion. TKA systems used were Genesis II, NexGen, low contact stress (LCS), PFC Sigma, Scorpio, and Vanguard. The knees in which the insertion was preserved in all implants or excised in at least one implant were classified into intact or the high-risk groups, respectively. RESULTS: The popliteus tendon was preserved in all specimens with the LCS system. In contrast, the popliteus tendon insertion was excised in >=1/3 of the specimens with the other systems. The anteroposterior diameter was significantly larger in the intact group than that in the high-risk group (58.1 +/- 4.5 mm vs. 53.7 +/- 2.7 mm; p = 0.018). The high risk group included more knees from female cadavers than the intact group (70 vs. 9 %; p = 0.008). CONCLUSION: During primary TKA, the femoral insertion of the popliteus tendon could be inevitably excised, regardless of technical problems. We demonstrate that the unique design of the LCS system preserves the popliteus tendon insertion. In addition, small knees and females may be risk factors for excision of the insertion. PMID- 26362656 TI - [Carotid aneurysm as a differential diagnosis of a cervical tumor]. AB - This article presents the case of a patient with a submandibular cervical tumor initially suspected to be a large lymph node or glomus tumor. However, the diagnostic workup prior to taking a biopsy sample revealed an extracranial aneurysm of the internal carotid artery. In order to prevent a permanent neurologic deficit arising from thromboembolism, the aneurysm was excluded by resection and arterial continuity was restored. Extracranial aneurysms of the internal carotid artery are rare, but serious differential diagnoses of cervical nodes. It is of paramount importance that this differential diagnosis be considered before initiating invasive diagnostics of these tumors. PMID- 26362657 TI - Investigation of the relationship between arterial stiffness and sleep architecture in patients with essential hypertension. AB - A change in sleep architecture might increase the risk of hypertension and worsen target organs. This study thus aimed to study the features of sleep architecture and examine its relationship with pulse wave velocity (PWV), a measure of arterial stiffness, in patients with essential hypertension and healthy people aged 45-65 years (n = 106). We collected data on demographics, the serum index, overnight polysomnography, vascular testing and ambulatory blood pressure in addition to measuring arterial stiffness and monitoring sleep respiration. We found that patients with hypertension had longer sleep latency and shorter duration. Their sleep efficiency and the ratio of N3 in non-rapid eye movement (NREM) and rapid eye movement were lower, while the micro-arousal index (MI), N1 and N2 in NREM, and the apnea-hypopnea index were higher than normal people in controls. PWV raised with a decrease in N3 and an increase in the MI. In summary, there were notable changes in sleep architecture and with a decrease in N3 and increase in MI can accelerate arterial stiffness and then worsen target organ damage in patients with hypertension. PMID- 26362658 TI - A molecular model for the free energy, bending elasticity, and persistence length of wormlike micelles. AB - An expression for the elastic free-energy density of a wormlike micelle is derived taking into account interactions between its constituent molecules. The resulting expression is quadratic in the curvature and torsion of the centerline of micelle and thus resembles free-energy density functions for polymer chains and helical filaments such as DNA. The model is applied on a wormlike micelle in the shape of a circular arc, open or closed. Conditions under which linear chains in dilute systems transform into toroidal rings are analyzed. Two concrete anisotropic soft-core interaction potentials are used to calculate the elastic moduli present in the derived model, in terms of the density of the molecules and their dimensions. Expressions for the persistence length of the wormlike micelle are found based on the flexural rigidities so obtained. Similar to previous observations, our results indicate that the persistence length of a wormlike micelle increases as the aspect ratio of its constituent molecules increases. A detailed application of the model on wormlike micelles of toroidal geometry, along with employing statistical-thermodynamical concepts of self-assembly is performed, and the results are found to be well consistent with the literature. Steps to obtain the material parameters through possible experiments are discussed. PMID- 26362659 TI - Immunogenicity and safety of early vaccination with two doses of a combined measles-mumps-rubella-varicella vaccine in healthy Indian children from 9 months of age: a phase III, randomised, non-inferiority trial. AB - OBJECTIVE: This study (NCT00969436) compared the immunogenicity and safety of measles-mumps-rubella (MMR) followed by MMR+varicella (V) vaccines to (1) 2 doses of combined MMRV and (2) MMR followed by MMRV, in Indian children. DESIGN: Phase III, open, randomised, non-inferiority study. SETTING: 6 tertiary care hospitals located in India. PARTICIPANTS: Healthy participants aged 9-10 months not previously vaccinated against/exposed to measles, mumps, rubella and varicella or without a history of these diseases. INTERVENTIONS: Participants were randomised (2:2:1) to receive 2 doses of either MMRV (MMRV/MMRV group) or MMR followed by MMRV (MMR/MMRV group) or MMR followed by MMR+V (MMR/MMR+V, control group) at 9 and 15 months of age. Antibody titres against measles, mumps and rubella were measured using ELISA and against varicella using an immunofluorescence assay. MAIN OUTCOME MEASURES: To demonstrate non-inferiority of the 2 vaccination regimens versus the control in terms of seroconversion rates, defined as a group difference with a lower bound of the 95% CI >-10% for each antigen, 43 days postdose 2. Parents/guardians recorded solicited local and general symptoms for a 4-day and 43-day period after each vaccine dose, respectively. RESULTS: Seroconversion rates postdose 1 ranged from 87.5% to 93.2% for measles, 83.3% to 86.1% for mumps and 98.7% to 100% for rubella across the 3 vaccine groups. The seroconversion rates postdose 2 were 100% for measles, mumps and rubella and at least 95.8% for varicella across the 3 vaccine groups. Non-inferiority of MMRV/MMRV and MMR/MMRV to MMR/MMR+V was achieved for all antigens, 43 days postdose 2. The 3 vaccination regimens were generally well tolerated in terms of solicited local and general symptoms. CONCLUSIONS: The immune responses elicited by the MMRV/MMRV and MMR/MMRV vaccination regimens were non-inferior to those elicited by the MMR/MMR+V regimen for all antigens. The 3 vaccination schedules also exhibited an acceptable safety profile in Indian children. TRIAL REGISTRATION NUMBER: NCT00969436. PMID- 26362660 TI - Risk of myocardial infarction (MI) and death following MI in people with chronic obstructive pulmonary disease (COPD): a systematic review and meta-analysis. AB - OBJECTIVES: Cardiovascular disease is an important comorbidity in patients with chronic obstructive pulmonary disease (COPD). We aimed to systematically review the evidence for: (1) risk of myocardial infarction (MI) in people with COPD; (2) risk of MI associated with acute exacerbation of COPD (AECOPD); (3) risk of death after MI in people with COPD. DESIGN: Systematic review and meta-analysis. METHODS: MEDLINE, EMBASE and SCI were searched up to January 2015. Two reviewers screened abstracts and full text records, extracted data and assessed studies for risk of bias. We used the generic inverse variance method to pool effect estimates, where possible. Evidence was synthesised in a narrative review where meta-analysis was not possible. RESULTS: Searches yielded 8362 records, and 24 observational studies were included. Meta-analysis showed increased risk of MI associated with COPD (HR 1.72, 95% CI 1.22 to 2.42) for cohort analyses, but not in case-control studies: OR 1.18 (0.80 to 1.76). Both included studies that investigated the risk of MI associated with AECOPD found an increased risk of MI after AECOPD (incidence rate ratios, IRR 2.27, 1.10 to 4.70, and IRR 13.04, 1.71 to 99.7). Meta-analysis showed weak evidence for increased risk of death for patients with COPD in hospital after MI (OR 1.13, 0.97 to 1.31). However, meta analysis showed an increased risk of death after MI for patients with COPD during follow-up (HR 1.26, 1.13 to 1.40). CONCLUSIONS: There is good evidence that COPD is associated with increased risk of MI; however, it is unclear to what extent this association is due to smoking status. There is some evidence that the risk of MI is higher during AECOPD than stable periods. There is poor evidence that COPD is associated with increased in hospital mortality after an MI, and good evidence that longer term mortality is higher for patients with COPD after an MI. PMID- 26362661 TI - Effect of zinc added to a daily small-quantity lipid-based nutrient supplement on diarrhoea, malaria, fever and respiratory infections in young children in rural Burkina Faso: a cluster-randomised trial. AB - OBJECTIVE: Preventive zinc supplementation in the form of tablets or syrup reduces the incidence of diarrhoea and acute lower respiratory tract infections (RTI), but its effect on malaria is inconsistent. When zinc is administered with other micronutrients or foods, its effect is also uncertain. We assessed the effects of different amounts and sources of zinc on the frequency of diarrhoea, malaria, fever and RTI in young children. DESIGN, SETTING AND POPULATIONS: This community-based, double-blind, placebo-controlled, cluster-randomised trial of 2435 children 9 months of age was carried out between April 2010 and July 2012 in rural southwestern Burkina Faso. INTERVENTIONS: Participants were randomly assigned at the concession level to receive daily 1 of 4 interventions for 9 months: (1) 20 g small-quantity lipid-based nutrient supplement (SQ-LNS) without zinc and placebo tablet, (2) 20 g SQ-LNS with 5 mg zinc and placebo tablet, (3) 20 g SQ-LNS with 10 mg zinc and placebo tablet or (4) 20 g SQ-LNS without zinc and 5 mg zinc tablet. Participants were visited weekly in their homes for morbidity surveillance for 9 months, and those with uncomplicated diarrhoea and malaria received treatment from the study field workers in the community. MAIN OUTCOMES: Incidence and longitudinal prevalence of diarrhoea, malaria, fever, and lower and upper RTI by intervention group. RESULTS: The incidence of diarrhoea, malaria and fever was 1.10 (+/-1.03 SD), 0.61 (+/-0.66 SD) and 1.49 (+/-1.12 SD) episodes per 100 child-days at risk, respectively, and did not differ by intervention group (p=0.589, p=0.856 and p=0.830, respectively). The longitudinal prevalence of acute lower RTI (0.1%; 95% IC 0.1-0.2%) and of upper RTI (7.8%; 95% IC 7.1-8.4%) did not differ among groups (p=0.234 and p=0.501, respectively). CONCLUSIONS: Inclusion of 5 or 10 mg zinc in SQ-LNS and provision of 5 mg zinc dispersible tablet along with SQ-LNS had no impact on the incidence of diarrhoea, malaria and fever or the longitudinal prevalence of RTI compared with SQ-LNS without zinc in this population. TRIAL REGISTRATION NUMBER: NCT00944281. PMID- 26362662 TI - What would encourage help-seeking for memory problems among UK-based South Asians? A qualitative study. AB - OBJECTIVES: People from Minority Ethnic groups tend to present late to dementia services, often in crisis. Culture-specific barriers to help-seeking seem to underlie this. We sought to determine these barriers to timely help-seeking for dementia among people from South Asian backgrounds and what the features of an intervention to overcome them would be. STUDY DESIGN: Qualitative study to delineate barriers to and facilitators of help-seeking for South Asian adults with dementia through focus groups and individual interviews. SETTING: Community settings in and around Greater London. PARTICIPANTS: To achieve a maximum variation sample, we purposively recruited 53 English or Bengali speaking South Asian adults without a known diagnosis of dementia through community centres and snowballing. RESULTS: Participants ranged in age from 18 to 83 years, were mostly female and were 60% Bangladeshi. We recruited people from different religions and occupational backgrounds and included those with experience of caring for someone with dementia as well as those without this experience. Participants identified four main barriers to timely diagnosis: barriers to help-seeking for memory problems; the threshold for seeking help for memory problems; ways to overcome barriers to help-seeking; what features an educational resource should have. CONCLUSIONS: We have identified the features of an intervention with the potential to improve timely dementia diagnosis in South Asians. The next steps are to devise and test such an intervention. PMID- 26362663 TI - Monitoring patient safety in primary care: an exploratory study using in-depth semistructured interviews. AB - OBJECTIVES: To explore how information and data are used to monitor patient safety and quality of primary care by professionals working in, or supporting, primary healthcare. DESIGN: Qualitative study of semistructured interviews with a directed content analysis of transcripts. SETTING: North-West London, UK. PARTICIPANTS: 21 individuals from various levels of the primary healthcare system were recruited, including general practitioners, practice nurses, practice managers, members of Clinical Commissioning Group (CCG) governing bodies, and senior members of regional patient safety teams. RESULTS: Participants described being overwhelmed with complicated data which lacked any meaningful analyses about safety and quality. There was also a lack of clarity over which patient safety events are expected to be reported or monitored. Participants also reported uncertainty on whose responsibility it was to act on patient safety information or concerns. At the practice level, there was a range of disincentives for responding to and acting on safety issues and concerns, with few reported benefits. Participants made recommendations to improve future monitoring. CONCLUSIONS: There is a need for clearer information in the form of specific guidelines, policies and procedures with regard to who monitors patient safety in primary care, what is monitored and how it should be monitored. PMID- 26362664 TI - Long-term effect of physical activity on health-related quality of life among menopausal women: a 4-year follow-up study to a randomised controlled trial. AB - OBJECTIVES: The aim of the study was to explore the long-term effects of physical activity intervention on quality of life (QoL) 4 years after an original randomised controlled trial (RCT). DESIGN: Cohort study after an RCT. SETTING: 95 of the 159 women from the original RCT participated in weight, height and waist circumference measurements, performed the UKK 2 km Walk Test and completed the SF 36 Health Survey questionnaire. Multilevel mixed regression models were performed in order to compare the original and current group in an RCT setting. PARTICIPANTS: There were 159 participants in the original RCT; 2.5 years later, 102 of the women responded to a questionnaire and 4-year after the trial, there were 95 respondents. The inclusion criteria in the original RCT were: being symptomatic, experiencing daily hot flushes, age between 40 and 63 years, not using hormone therapy now or in the past 3 months, sedentary lifestyle and having last menstruated 3-36 months earlier. MAIN OUTCOME MEASURE: Health-related QoL as measured with the SF-36 instrument. RESULTS: Women in the intervention group had a significantly higher probability of improved physical functioning (OR 1.41; 95% CI 1.00 to 1.99) as compared with women in the control group. In addition, women in the intervention group had higher odds of good role functioning (OR 1.21; 95% CI 0.88 to 1.67), physical health (OR 1.33; 95% CI 0.96 to 1.84) and general health (OR 1.14; 95% CI 0.81 to 1.62), relative to women in the control group, although the differences did not reach statistical significance. CONCLUSIONS: Women in the intervention group showed positive long-term effects on physical and mental dimensions of QoL after 4 years. TRIAL REGISTRATION NUMBER: ISRCTN54690027. PMID- 26362665 TI - E-cigarette marketing in UK stores: an observational audit and retailers' views. AB - OBJECTIVES: To explore how e-cigarettes are being promoted at point of sale in the UK and how retailers perceive market trends. SETTING: Fixed retail outlets subject to a ban on the display of tobacco products. PARTICIPANTS: Observational audit of all stores selling tobacco products (n=96) in 4 Scottish communities, conducted over 2 waves 12 months apart (2013-2014), and qualitative interviews with small retailers (n=25) in 4 matched communities. PRIMARY AND SECONDARY OUTCOME MEASURES: The audit measured e-cigarette display characteristics, advertising materials and proximity to other products, and differences by area level disadvantage. Interviews explored retailers' perceptions of e-cigarette market opportunities and risks, and customer responses. RESULTS: The number of e cigarette point-of-sale display units and number of brands displayed increased between waves. E-cigarettes were displayed close to products of interest to children in 36% of stores. Stores in more affluent areas were less likely to have external e-cigarette advertising than those in deprived areas. Although e cigarettes delivered high profit margins, retailers were confused by the diversity of brands and products, and uncertain of the sector's viability. Some customers were perceived to purchase e-cigarettes as cessation aids, and others, particularly low-income smokers, as a cheaper adjunct to conventional tobacco. CONCLUSIONS: E-cigarette point-of-sale displays and number of brands displayed increased over 12 months, a potential cause for concern given their lack of regulation. Further scrutiny is needed of the content and effects of such advertising, and the potentially normalising effects of placing e-cigarettes next to products of interest to children. PMID- 26362666 TI - External validity of a randomised controlled trial on the treatment of severe infections caused by MRSA. AB - OBJECTIVES: To assess the external validity of a pragmatic, investigator initiated RCT on treatment of severe infections caused by methicillin-resistant Staphylococcus aureus (MRSA), we compared patient characteristics and treatment effect estimates for patients included in the RCT versus those excluded. PARTICIPANTS AND OUTCOMES: The RCT included hospitalised patients with documented or highly-probable invasive MRSA infections who were randomised to vancomycin versus trimethoprim-sulfamethoxazole (TMP-SMX) treatment, between 2007 and 2014. A concomitant observational study prospectively included all consecutive patients, between 2008 and 2011, who were excluded from the RCT due to no consent, meningitis, left-sided endocarditis, severe neutropaenia, chronic renal dialysis or treatment with study medications for longer than 48 h. The primary outcomes were clinical failure at day 7 and 30-day mortality for both studies. We compared baseline and infection characteristics, outcome rates and treatment effect estimates for included versus excluded patients. RESULTS: The RCT included 252 patients who were compared with 220 excluded patients who were observed. Inability to provide informed consent was the main reason for patient exclusion. Excluded patients' functional and cognitive performance was significantly poorer than that of included patients. Sepsis was more severe among excluded patients (higher rates of mechanical ventilation, indwelling catheters, septic shock and organ failure). Clinical failure occurred in 83/252 (32.9%) versus 175/220 (79.5%) and deaths in 32 (12.7%) versus 64 (29.1%) for included versus excluded patients, p<0.001 for both comparisons. Comparing vancomycin to TMP-SMX, in the RCT mortality, was non-significantly lower with vancomycin (OR 0.76, 95% CIs 0.36 to 1.62), while in the observational analysis of excluded patients, mortality was significantly higher with vancomycin (OR 2.63, 1.04 to 6.65), p=0.04 for the difference. CONCLUSIONS: Patient characteristics, outcome event rates and treatment effects differed significantly in the setting of a RCT, despite its pragmatic design, compared to patients treated outside the trial settings. PMID- 26362667 TI - Understanding trends in blood pressure and their associations with body mass index in Chinese children, from 1985 to 2010: a cross-sectional observational study. AB - OBJECTIVE: Understanding trends in blood pressure (BP) in childhood is crucial to addressing and reducing the burden of adulthood hypertension and associated mortality in the future. In view of growing obesity in Chinese children, we sought to investigate the trends in BP and the influence of body mass index (BMI) on them. DESIGN, SETTING AND PARTICIPANTS: We included 1,010,153 children aged 8 17 years, with completed records from a large national successive cross-sectional survey, the Chinese National Survey on Students' Constitution and Health, between 1985 and 2010. MAIN OUTCOME MEASUREMENTS: BP was measured according to the recommendation of the National High Blood Pressure Education Program Working Group, and the elevated BP was based on sex-, age- and height-specific 95th centile of the recommendation. RESULTS: The adjusted mean systolic BP in boys and girls decreased by 3.9 and 5.6 mm Hg between 1985 and 2005, and increased by 1.3 and 1.0 mm Hg between 2005 and 2010, respectively. Corresponding adjusted prevalence of elevated systolic BP in boys and girls declined from 5.1% and 5.5% to 3.5% and 2.5% between 1985 and 2005, and increased to 4.9% and 3.5% in 2010, respectively. Adjusted mean BMI of boys and girls in 2010 was 2.0 and 1.2 kg/m(2) higher than those in 1985, respectively. The prevalence of obesity rose from 0% to 3.4% in boys and 0.9% in girls. Further adjusting for BMI did not change these trends in systolic BP. A similar pattern was also observed in diastolic BP. CONCLUSIONS: After declining for 20 years, BP levels in Chinese children started to climb upwards. These trends in BP cannot be fully explained by BMI. The investigation of other determinants of BP may provide additional opportunity to curb the current upward BP trend in Chinese children. PMID- 26362668 TI - Long-term musculoskeletal morbidity after adult burn injury: a population-based cohort study. AB - OBJECTIVE: To investigate if adults who are hospitalised for a burn injury have increased long-term hospital use for musculoskeletal diseases. DESIGN: A population-based retrospective cohort study using linked administrative health data from the Western Australian Data Linkage System. SUBJECTS: Records of 17,753 persons aged at least 20 years when hospitalised for a first burn injury in Western Australia during the period 1980-2012, and 70,758 persons who were age and gender-frequency matched with no injury admissions randomly selected from Western Australia's electoral roll. MAIN OUTCOME MEASURES: Admission rates and cumulative length of stay for musculoskeletal diseases. Negative binomial and Cox proportional hazards regression modelling were used to generate incidence rate ratios (IRR) and HRs with 95% CIs, respectively. RESULTS: After adjustment for pre-existing health status and demographic characteristics, the burn cohort had almost twice the hospitalisation rate for a musculoskeletal condition (IRR, 95% CI 1.98, 1.86 to 2.10), and spent 3.70 times as long in hospital with a musculoskeletal diagnosis (95% CI 3.10 to 4.42) over the 33-year period, than the uninjured comparison cohort. Adjusted survival analyses of incident post-burn musculoskeletal disease admissions found significant increases for the 15-year post burn discharge period (0-6 months: HR, 95% CI 2.51, 2.04 to 3.11; 6 months-2 years: HR, 95% CI 1.77, 1.53 to 2.05; 2-15 years: HR, 95% CI 1.32, 1.23 to 1.42). Incident admission rates were significantly elevated for 20 years post-burn for minor and severe burn injury for a range of musculoskeletal diseases that included arthropathies, dorsopathies, osteopathies and soft tissue disorders. CONCLUSIONS: Minor and severe burn injuries were associated with significantly increased post-burn incident admission rates, long-term hospital use and prolonged length of stay for a range of musculoskeletal diseases. Further research is required that facilitates identification of at-risk patients and appropriate treatment pathways, to reduce the long-term morbidity associated with burns. PMID- 26362669 TI - Development and validation of a brief screener to measure the Health Literacy Responsiveness of Primary Care Practices (HLPC). AB - BACKGROUND: The evolving approach of health literate health care organizations (HLHO) receives considerable support from health policy makers. Up to now, there are no performance measures available to assess the application of health literacy strategies by health care professionals in the primary care setting. This paper describes the development and validation of the Health Literate Primary Care Practice screener (HLPC). The screener can be used as a self assessment tool for primary care organizations (PCO) that aim to elucidate the health literacy responsiveness of their organization. METHODS: The HLPC is a 4 item screener developed in a multi-level process following a theory-driven approach including a literature review, consultations with scientists and cognitive tests with patients in PCO. The screener was applied in a national random sample of N = 1125 adults living in Germany. Item and psychometric properties were analyzed by determining item discrimination and reliability as well as performing a confirmatory factor analysis (CFA) to test the instruments unidimensionality. Criterion validity was investigated by performing bivariate correlations between the HLPC score and heath care quality measures. RESULTS: The HLPC scale demonstrated good item discrimination and internal consistency (alpha = 0.86). CFA verified a one-factor structure of the scale and analysis on the criterion validity revealed a significant correlation between the HLPC score and patients satisfaction with the general practitioner, accessibility of the PCO and support in care-coordination received in the PCO. CONCLUSIONS: The HLPC is a valid screener to provide insights in the extent of the utilization of health literacy strategies in primary care practices. PMID- 26362670 TI - Fertility and Minority: A Study in Two Provinces of Iran Using Matching Estimator Technique. AB - The main aim of this study was to compare fertility in minor (Sunnah) and major (Shia) religious groups of Iran after matching the two groups by some confounding factors. 12,099 data of population and census survey of Iran in 2011 in two provinces of Guilan and Kurdistan were used in this study. Propensity scoring matching method was used for matching two groups. First confounder variables were found and after that the groups were matched. Principal component analysis was used to make a socioeconomic (SES) variable. At the end, two groups were compared to each other by nearest neighborhood method. Also Poisson regression was used to find the effective factors of fertility. Before using matching method, the results showed that fertility in Kurdistan was higher than Guilan, but after matching, fertility in Guilan was higher. The results of regression model showed that in Guilan, living in urban region, age and level of education had effect on fertility, but in Kurdistan, education, age and SES were effective factors. PMID- 26362671 TI - Identifying Barriers to Delirium Screening and Prevention in the Pediatric ICU: Evaluation of PICU Staff Knowledge. AB - Delirium in the pediatric intensive care unit (PICU) setting is often unrecognized and undertreated. The importance of screening and identification of ICU delirium has been identified in both adult and pediatric literature. Delirium increases ICU morbidity, length of mechanical ventilation and length of stay. The objective of this study was to determine the current knowledge level about delirium and its risk factors among pediatric critical care nurses through a short questionnaire. We hypothesized that before a targeted educational intervention, PICU care providers do not have an adequate knowledge base for accurate screening and diagnosis of delirium in critically ill children. A 17 question online survey was given to all nurses in a tertiary 36-bed PICU to assess current knowledge about delirium in children. The response rate was 73% (105/143). When asked to identify the correct way to diagnose pediatric delirium, 11.4% of nurses surveyed (12/105) incorrectly believed that Glasgow Coma Score is the appropriate screening tool. A large proportion of respondents (40/105) believed that benzodiazepines are helpful in treatment of delirium. The results of the survey identified specific knowledge gaps about risk factors and treatment of pediatric delirium in the critically ill child. There is a critical need for education about pediatric delirium and its risk factors among PICU staff prior to unit-wide implementation of a delirium screening and prevention program, specifically with regards to screening methods and pharmacologic risk factors. These results are likely generalizable to all physicians, nurses and staff who care for critically ill children. PMID- 26362673 TI - Smoking effects on quality of life of allergic rhinitis patients after sublingual immunotherapy. AB - BACKGROUND: Although tobacco smoking is of great concern, there is no evidence for the effects of smoking on quality of life (QoL) results after sublingual immunotherapy (SLIT). OBJECTIVE: This study aims tomicron explore any association between smoking habits (duration and quantity) and QoL results after SLIT in allergic rhinitis (AR). METHODOLOGY: One hundred and sixty three patients following SLIT for AR were participated. SLIT efficacy related to smoking was prospectively evaluated by means of validated widely used QoL questionnaires, either for assessing psychology (Zung Anxiety Scale, State-Trait Anxiety Inventory, Zung Depression Scale and Beck Depression Inventory) or generic (Short Form-36) ones, pre- and immediately upon cessation of SLIT. Smoking habits were expressed in pack-years. RESULTS: Significant improvement of total symptoms score (T5SS) and of all QoL questionnaires' results were observed in our patients' group, both for smokers and non smokers. The comparison of changes between smokers and non smokers, controlling for the effect of all patients' characteristics, showed that there was no significant differences on improvement values. Additionally multivariate linear regression analysis revealed that the effect of pack-years on the QoL scales was not significant. CONCLUSIONS: Our results suggest that smoking habits (quantity of daily smoking and duration) do not influence the success of SLIT with regards to QoL outcomes. PMID- 26362672 TI - Functional organization of the mammalian auditory midbrain. AB - The inferior colliculus (IC) is a critical nexus between the auditory brainstem and the forebrain. Parallel auditory pathways that emerge from the brainstem are integrated in the IC. In this integration, de-novo auditory information processed as local and ascending inputs converge via the complex neural circuit of the IC. However, it is still unclear how information is processed within the neural circuit. The purpose of this review is to give an anatomical and physiological overview of the IC neural circuit. We address the functional organization of the IC where the excitatory and inhibitory synaptic inputs interact to shape the responses of IC neurons to sound. PMID- 26362674 TI - Deletion of arcA increased the production of acetyl-CoA-derived chemicals in recombinant Escherichia coli. AB - OBJECTIVE: Acetyl-CoA is used to produce many valuable metabolites in Escherichia coli. However, acetate overflow is a major shortcoming. Knockout of the global regulator gene, arcA, may solve this problem. RESULTS: The arcA gene of E. coli BL21(DE3) was knocked out, and the production of phloroglucinol (PG) and 3 hydroxypropionate (3HP), both derived from acetyl-CoA, were used to evaluate its effect. The arcA mutants had higher cell yields and higher glucose utilization efficiencies than the corresponding control strains, and the productions of PG and 3HP were 0.92 g/l and 0.27 g/l, respectively; more than twice that of the control strains. Furthermore, arcA knockout also showed significant repression on formation of acetate, the major byproduct in fermentation. Acetate concentrations were decreased 69.4 % and 87 % by arcA knockout during the production of PG and 3HP, respectively. CONCLUSIONS: The arcA gene knockout is a solution to acetate overflow and may improve production of a wide range of acetyl-CoA-derived metabolites. PMID- 26362675 TI - Peripheral blood NK cells expressing HLA-G, IL-10 and TGF-beta in healthy donors and breast cancer patients. AB - Human natural killer (NK) cells are not only professional cytotoxic cells integrated into effector branch of innate immunity, but they are also regulatory cells, managing different immune processes. Immunoregulatory NK cells, expressing HLA-G and IL-10, have been generated in vitro from human hematopoietic progenitors and found in vivo among decidual NK cells of pregnant women. Human peripheral blood NK cells have been shown to acquire suppressive properties after HLA-G uptake during trogocytosis. Moreover, it has been shown that circulating NK cells contain a trace amount of cells producing TGF-beta and IL-10, which exert a suppressive influence upon innate and adaptive immunity. In this study, we report on a minor subset of peripheral blood HLA-G(+) NK cells possessing suppressive activity toward effector functions of NK cells. Further we demonstrate an increased number of circulating HLA-G(+), IL-10(+), and TGF-beta(+) NK cells in breast cancer patients which might impair efficiency of anti-tumor immunity. PMID- 26362677 TI - Characteristics of hopanoid hydrocarbons in ambient PM10 and motor vehicle emissions and coal ash in Taiyuan, China. AB - Hopanoid hydrocarbon content in ambient particulate matter (PM) of less than or equal to 10 MUm aerodynamic diameter (PM10) was sampled at seven sites representative of different functional districts, and measured by gas chromatography-mass spectrometry. 17alpha(H),21beta(H)-hopane (C30alphabeta) and 17alpha(H),21beta(H)-30-norhopane (C29alphabeta) were dominant in all samples. Hopanes in motor vehicle emissions from various fuel-type engines (gasoline, diesel and natural gas) and coal ash were qualitatively measured, and the amount of C30alphabeta was about two to three times greater than that of C29alphabeta. Distinct seasonal variations (winter/summer differences) were observed at higher concentrations (45.54-108.29 ng/m(3)) of total hopanes in winter and lower (2.59 28.26 ng/m(3)) in summer. There were also clear spatial variations of hopanes in Taiyuan, with samples with greater hopane concentrations in downtown areas, but less in summer. The spatial distribution reversed in winter. Distributions and relative abundances of selected hopanes from PM10 and source emissions indicated that in summer, vehicle exhaust was the dominant fossil fuel combustion source (C30alphabeta was >C29alphabeta), and that the contribution of coal combustion was slightly greater at suburban sites. However, the contribution of coal combustion sources increased significantly at all sites in winter, especially in suburban areas, where C29alphabeta exceeded C30alphabeta. Hopanoid indexes revealed a classification of vehicle exhaust and coal combustion emissions in PM10. The results imply that during rapid urbanization, it is crucial to strengthen the construction of infrastructure such as central heating in new city districts and to increase the use of natural gas instead of residential coal burning. PMID- 26362676 TI - Glucose-deprivation increases thyroid cancer cells sensitivity to metformin. AB - Metformin inhibits thyroid cancer cell growth. We sought to determine if variable glucose concentrations in medium alter the anti-cancer efficacy of metformin. Thyroid cancer cells (FTC133 and BCPAP) were cultured in high-glucose (20 mM) and low-glucose (5 mM) medium before treatment with metformin. Cell viability and apoptosis assays were performed. Expression of glycolytic genes was examined by real-time PCR, western blot, and immunostaining. Metformin inhibited cellular proliferation in high-glucose medium and induced cell death in low-glucose medium. In low-, but not in high-glucose medium, metformin induced endoplasmic reticulum stress, autophagy, and oncosis. At micromolar concentrations, metformin induced phosphorylation of AMP-activated protein kinase and blocked p-pS6 in low glucose medium. Metformin increased the rate of glucose consumption from the medium and prompted medium acidification. Medium supplementation with glucose reversed metformin-inducible morphological changes. Treatment with an inhibitor of glycolysis (2-deoxy-d-glucose (2-DG)) increased thyroid cancer cell sensitivity to metformin. The combination of 2-DG with metformin led to cell death. Thyroid cancer cell lines were characterized by over-expression of glycolytic genes, and metformin decreased the protein level of pyruvate kinase muscle 2 (PKM2). PKM2 expression was detected in recurrent thyroid cancer tissue samples. In conclusion, we have demonstrated that the glucose concentration in the cellular milieu is a factor modulating metformin's anti-cancer activity. These data suggest that the combination of metformin with inhibitors of glycolysis could represent a new strategy for the treatment of thyroid cancer. PMID- 26362678 TI - Sources of organic pollution in particulate matter and soil of Silesian Agglomeration (Poland): evidence from geochemical markers. AB - The exact input of particular sources to polycyclic aromatic hydrocarbons (PAHs) concentrations in urban and industrial agglomerations is still not well recognized. The major breakthrough is possible using geochemical markers. In the air aerosol and soil samples from areas located in the direct influence of industry/traffic in Silesian Agglomeration (Poland), PAHs and other organic compounds were analyzed, including geochemical markers (biomarkers) and polar compounds from fossil fuels and biomass. Gas chromatography (GC-FID) and gas chromatography-mass spectrometry (GC-MS) were applied to investigate the composition of particulate matter and soil extracts. The results suggest that the predominant source of PAHs is fossil fuel. The presence and distribution of steranes, pentacyclic triterpenoids (i.e., hopanes and moretanes) and alkyl PAHs point to traffic emissions and fossil fuel combustion, mainly bituminous coal for power and heat purposes, as the main source of PAHs in the region. Moreover, the presence of fossil fuel biomarker in particulate matter and soil extracts from a rural site, previously considered to be free of organic pollution, requires a cautious interpretation for PAHs results. Apart from the fossil fuel, also other sources of contamination were identified in particulate matter extracts by their markers: phenols and levoglucosan for biomass and diisopropylnaphthalenes for printing materials combustion. The absence of polar biomass combustion indicators in soil extracts might be related to their higher reactivity. PMID- 26362679 TI - Variation of the slope of the tentorium during childhood. AB - BACKGROUND AND PURPOSE: Neural structures in the posterior fossa grow at different rates during development. While there are computationally intensive approaches to analyze growth of the cerebellum and brainstem, there is a paucity of information about summary measures of normal posterior fossa development suitable for real-time clinical use. The present study investigates changes in the trajectory of the tentorium as measured by the occipital and tentorial angles at different stages of development. METHODS: A retrospective study was conducted drawing from a Boston Children's Hospital database of over 1500 magnetic resonance imaging (MRI) studies. The imaging study population included fetuses older than 20 gestational weeks and children between the ages of 0 and 10 years. Two parameters were measured for all subjects: (1) the tentorial angle (the angle between the tentorium and a line from the internal occipital protuberance to the tuberculum sellae) and (2) the occipital angle (the angle between the tentorium and a line from the internal occipital protuberance to the opisthion). Descriptive statistics were used to analyze the study cohort. RESULTS: We reviewed 1510 brain MRI studies, and 367 studies met the inclusion criteria (125 fetal and 242 postnatal studies). During fetal development, the inclination of the tentorium showed an ascending course, while it plateaus after birth. CONCLUSIONS: During the second and third trimesters, the tentorial and occipital angles steadily increase reflecting the dynamic growth of the posterior fossa structures. Postnatally, the tentorial angle decreases and the tentorium slopes downward and plateaus, possibly due to stabilization of posterior fossa development and ongoing growth of the cerebrum. Together, these findings suggest that the tentorial angle can serve as an imaging biomarker of posterior fossa development during the second half of fetal life. PMID- 26362680 TI - Development and validation of a spina bifida-specific pediatric quality of life questionnaire: the Spina Bifida Pediatric Questionnaire, SBPQ. AB - PURPOSE: Based on existing questionnaires and patient interview, a health-related quality of life (HRQoL) questionnaire in spina bifida (SB) children is created and validated, the Spina Bifida Pediatric Questionnaire (SBPQ). METHODS: SB patients from the SB reference centre Ghent University Hospital, Belgium, with mental ability between 6 and 18 years old and their parents were asked to participate in the study, together with a control group. RESULTS: Thirty-nine patients and parents answered the questionnaire once, 20 patients and their parents the test-retest. Thirty-five controls answered the questionnaire once, 34 controls and their parents the test-retest. The final questionnaire was retained when 3 consecutive patients approved all items. Visual clues were added for children with a mental ability below 10 years of age. The test-retest showed a good to excellent agreement for child self-report in 5 domains (not for social functioning), for parent proxy report in all domains (6), for control self-report in 4 domains (not for domain home) and for control parent proxy report in all domains (5). Internal consistency reliability was good in child self-report and in parent proxy report, except for physical functioning in child self-report. There was parent-child agreement for 4 out of 6 domains. Regarding social and emotional functioning, QoL was rated lower by parents than by children themselves. CONCLUSION: A SB HRQoL questionnaire was developed and validated. Because of visual aid, this questionnaire can be used by both young children and adolescents. PMID- 26362681 TI - Dye-linked D-amino acid dehydrogenases: biochemical characteristics and applications in biotechnology. AB - Dye-linked D-amino acid dehydrogenases (Dye-DADHs) catalyze the dehydrogenation of free D-amino acids in the presence of an artificial electron acceptor. Although Dye-DADHs functioning in catabolism of L-alanine and as primary enzymes in electron transport chains are widely distributed in mesophilic Gram-negative bacteria, biochemical and biotechnological information on these enzymes remains scanty. This is in large part due to their instability after isolation. On the other hand, in the last decade, several novel types of Dye-DADH have been found in thermophilic bacteria and hyperthermophilic archaea, where they contribute not only to L-alanine catabolism but also to the catabolism of other amino acids, including D-arginine and L-hydroxyproline. In this minireview, we summarize recent developments in our understanding of the biochemical characteristics of Dye-DADHs and their specific application to electrochemical biosensors. PMID- 26362682 TI - Advances and needs for endotoxin-free production strains. AB - The choice of an appropriate microbial host cell and suitable production conditions is crucial for the downstream processing of pharmaceutical- and food grade products. Although Escherichia coli serves as a highly valuable leading platform for the production of value-added products, like most Gram-negative bacteria, this bacterium contains a potent immunostimulatory lipopolysaccharide (LPS), referred to as an endotoxin. In contrast, Gram-positive bacteria, notably Bacillus, lactic acid bacteria (LAB), Corynebacterium, and yeasts have been extensively used as generally recognized as safe (GRAS) endotoxin-free platforms for the production of a variety of products. This review summarizes the currently available knowledge on the utilization of these representative Gram-positive bacteria for the production of eco- and bio-friendly products, particularly natural polyesters, polyhydroxyalkanoates, bacteriocins, and membrane proteins. The successful case studies presented here serve to inspire the use of these microorganisms as a main-player or by-player depending on their individual properties for the industrial production of these desirable targets. PMID- 26362683 TI - To spin or not to spin: spider silk fibers and more. AB - Spider silk fibers have a sophisticated hierarchical structure composed of proteins with highly repetitive sequences. Their extraordinary mechanical properties, defined by a unique combination of strength and extensibility, are superior to most man-made fibers. Therefore, spider silk has fascinated mankind for thousands of years. However, due to their aggressive territorial behavior, farming of spiders is not feasible on a large scale. For this reason, biotechnological approaches were recently developed for the production of recombinant spider silk proteins. These recombinant proteins can be assembled into a variety of morphologies with a great range of properties for technical and medical applications. Here, the different approaches of biotechnological production and the advances in material processing toward various applications will be reviewed. PMID- 26362684 TI - Antimicrobial potentials of Helicteres isora silver nanoparticles against extensively drug-resistant (XDR) clinical isolates of Pseudomonas aeruginosa. AB - Pseudomonas aeruginosa is a leading opportunistic pathogen and its expanding drug resistance is a growing menace to public health. Its ubiquitous nature and multiple resistance mechanisms make it a difficult target for antimicrobial chemotherapy and require a fresh approach for developing new antimicrobial agents against it. The broad-spectrum antibacterial effects of silver nanoparticles (SNPs) make them an excellent candidate for use in the medical field. However, attempts made to check their potency against extensively drug-resistant (XDR) microbes are meager. This study describes the biosynthesis and biostabilization of SNPs by Helicteres isora aqueous fruit extract and their characterization by ultraviolet-visible spectroscopy, transmission electron microscopy, dynamic light scattering, X-ray diffraction, and Fourier transform infrared spectroscopy. Majority of SNPs synthesized were of 8--20-nm size. SNPs exhibited dose-dependent antibacterial activities against four XDR P. aeruginosa (XDR-PA) clinical isolates as revealed by growth curves, with a minimum inhibitory concentration of 300 MUg/ml. The SNPs exhibited antimicrobial activity against all strains, with maximum zone of inhibition (16.4 mm) in XRD-PA-2 at 1000 MUg/ml. Amongst four strains, their susceptibilities to SNPs were in the following order: XDR-PA-2 > XDR-PA-4 > XDR-PA-3 > XDR-PA-1. The exposure of bacterial cells to 300 MUg/ml SNPs resulted into a substantial leakage of reducing sugars and proteins, inactivation of respiratory chain dehydrogenases, and eventual cell death. SNPs also induced lipid peroxidation, a possible underlying factor to membrane porosity. The effects were more pronounced in XDR-PA-2 which may be correlated with its higher susceptibility to SNPs. These results are indicative of SNP induced turbulence of membranous permeability as an important causal factor in XDR-PA growth inhibition and death. PMID- 26362685 TI - Atypical effect of temperature tuning on the insertion of the catalytic iron sulfur center in a recombinant [FeFe]-hydrogenase. AB - The expression of recombinant [FeFe]-hydrogenases is an important step for the production of large amount of these enzymes for their exploitation in biotechnology and for the characterization of the protein-metal cofactor interactions. The correct assembly of the organometallic catalytic site, named H cluster, requires a dedicated set of maturases that must be coexpressed in the microbial hosts or used for in vitro assembly of the active enzymes. In this work, the effect of the post-induction temperature on the recombinant expression of CaHydA [FeFe]-hydrogenase in E. coli is investigated. The results show a peculiar behavior: the enzyme expression is maximum at lower temperatures (20 degrees C), while the specific activity of the purified CaHydA is higher at higher temperature (30 degrees C), as a consequence of improved protein folding and active site incorporation. PMID- 26362686 TI - Experiencing the body during pregnancy: A qualitative research study among Spanish sportswomen. AB - The aim of the current qualitative phenomenological study was to describe the body experiences during pregnancy among Spanish elite sportswomen. Twenty Spanish sportswomen with the following criteria were included: (1) aged between 18 and 65 years; (2) had been pregnant during their professional sporting career; and (3) after the end of their pregnancy, had returned to their professional sports career for at least 1 year. A qualitative thematic analysis was conducted. Data were collected from May 2010 to April 2012 using in-depth personal interviews, investigator's field notes, and extracts from the participants' personal letters. Identified themes included: (1) a new body; (2) body control; (3) to feel their bodies and communicate with them; and (4) body's beauty ideal. Understanding the meaning of the body experience for elite Spanish sportswomen might provide us with deeper insight into their expectations and might help in the development of training systems focused on them. PMID- 26362687 TI - Apportionment of lumbar L2-S1 rotation across individual motion segments during a dynamic lifting task. AB - Segmental apportionment of lumbar (L2-S1) rotation is a critical input parameter for musculoskeletal models and a candidate metric for clinical assessment of spinal health, but such data are sparse. This paper aims to quantify the time variant and load-dependent characteristics of intervertebral contributions to L2 S1 extension during a dynamic lifting task. Eleven healthy participants lifted multiple weights (4.5, 9.1, and 13.6 kg) from a trunk-flexed to an upright position while being imaged by a dynamic stereo X-ray system at 30 frames/s. Vertebral (L2-S1) motion was tracked using a previously validated volumetric model-based tracking method that employs 3D bone models reconstructed from subject-specific CT images to obtain high-accuracy (<=0.26 degrees , 0.2 mm) 3D vertebral kinematics. Individual intervertebral motions as percentages of the total L2-S1 extension were computed at each % increment of the motion to show the segmental apportionment. Results showed L3-L4 (25.8+/-2.2%) and L4-L5 (31+/-3.1%) together contributed a larger share (~60% combined) compared to L2-L3 (21.7+/ 3.7%) and L5-S1 (22.6+/-4.7%); L4-L5 consistently provided the largest contribution of the measured segments. Relative changes over time in L3-L4 (6+/ 12.5%) and L4-L5 (0.5+/-10.2%) contribution were minimal; in contrast, L2-L3 (18+/-20.1%) contribution increased while L5-S1 (-33+/-22.9%) contribution decreased in a somewhat complementary fashion as motion progressed. No significant effect of the magnitude of load lifted on individual segmental contribution patterns was detected. The current study updated the knowledge regarding apportionment of lumbar (L2-S1) motion among individual segments, serving both as input into musculoskeletal models and as potential biomechanical markers of low back disorders. PMID- 26362688 TI - Leisure and social participation in patients 4-10 years after aneurysmal subarachnoid haemorrhage. AB - OBJECTIVE: To investigate the long-term resumption of leisure and social activities in patients with aneurysmal subarachnoid haemorrhage (aSAH) and to determine the role of executive dysfunction and aneurysms in anterior brain regions in particular. METHOD: Leisure and social functioning of 200 patients with aSAH having anterior or posterior aneurysms was determined using the Role Resumption List (RRL). Executive functioning was investigated using the Dysexecutive Questionnaire (DEX) and sub-scales Social Convention (SC) and Executive Cognition (EC). Mood, fatigue and cognitive problems were investigated with the Hospital Anxiety and Depression Scale (HADS) and Brain Injury Symptom Checklist (BISC). RESULTS: Of all patients, 46.5% reported complete return to previous leisure activities and 61.5% reported no changes in social interactions. HADS depression score, fatigue, DEX-EC sub-scale score and work status post-aSAH were predictors of leisure resumption. For social re-integration, HADS depression score, cognitive problems and fatigue were predictors. Aneurysm location did not influence leisure and social re-integration. CONCLUSIONS: A substantial number of the patients still experience problems in resuming previous activities in the chronic phase post-aSAH, influenced by cognitive, executive and depressive problems, as well as current work status and fatigue. Aneurysm location does not seem to influence this resumption. PMID- 26362689 TI - Molecular aspects of glucose homeostasis in skeletal muscle--A focus on the molecular mechanisms of insulin resistance. AB - Among all the varied actions of insulin, regulation of glucose homeostasis is the most critical and intensively studied. With the availability of glucose from nutrient metabolism, insulin action in muscle results in increased glucose disposal via uptake from the circulation and storage of excess, thereby maintaining euglycemia. This major action of insulin is executed by redistribution of the glucose transporter protein, GLUT4 from intracellular storage sites to the plasma membrane and storage of glucose in the form of glycogen which also involves modulation of actin dynamics that govern trafficking of all the signal proteins of insulin signal transduction. The cellular mechanisms responsible for these trafficking events and the defects associated with insulin resistance are largely enigmatic, and this review provides a consolidated overview of the various molecular mechanisms involved in insulin dependent glucose homeostasis in skeletal muscle, as insulin resistance at this major peripheral site impacts whole body glucose homeostasis. PMID- 26362691 TI - Patient navigation and financial incentives to promote smoking cessation in an underserved primary care population: A randomized controlled trial protocol. AB - Despite the high risk of tobacco-related morbidity and mortality among low-income persons, few studies have connected low-income smokers to evidence-based treatments. We will examine a smoking cessation intervention integrated into primary care. To begin, we completed qualitative formative research to refine an intervention utilizing the services of a patient navigator trained to promote smoking cessation. Next, we will conduct a randomized controlled trial combining two interventions: patient navigation and financial incentives. The goal of the intervention is to promote smoking cessation among patients who receive primary care in a large urban safety-net hospital. Our intervention will encourage patients to utilize existing smoking cessation resources (e.g., quit lines, smoking cessation groups, discussing smoking cessation with their primary care providers). To test our intervention, we will conduct a randomized controlled trial, randomizing 352 patients to the intervention condition (patient navigation and financial incentives) or an enhanced traditional care control condition. We will perform follow-up at 6, 12, and 18 months following the start of the intervention. Evaluation of the intervention will target several implementation variables: reach (participation rate and representativeness), effectiveness (smoking cessation at 12 months [primary outcome]), unintended consequences (e.g., purchase of illicit substances with incentive money), adoption (use of intervention across primary care suites), implementation (delivery of intervention), and maintenance (smoking cessation after conclusion of intervention). Improving the implementation of smoking cessation interventions in primary care settings serving large underserved populations could have substantial public health impact, reducing cancer-related morbidity/mortality and associated health disparities. PMID- 26362692 TI - Examination of a brief anxiety sensitivity cognitive concerns intervention on suicidality among individuals with obsessive-compulsive symptoms. AB - A growing body of research has demonstrated elevated rates of suicidality among individuals with obsessive-compulsive disorder (OCD). Recently, it has been proposed that the cognitive concerns component of anxiety sensitivity (AS) may be one factor contributing to this association. AS cognitive concerns, which reflect fears of mental incapacitation, has been found to be associated with OCD and increased suicidality in a number of populations. However, questions remain as to whether reductions in AS cognitive concerns will lead to subsequent reductions in suicidality among individuals with OCD symptoms. In the current study, the sample (N=54) was comprised of individuals with elevated OCD symptoms recruited from the community who were participating in a larger randomized clinical trial. Individuals were randomly assigned to a one-session AS cognitive concerns intervention or a health information control intervention and assessed at post treatment and one-month follow-up. Results indicated that the active intervention produced significantly greater reductions in AS cognitive concerns immediately post-intervention. Moreover, changes in AS cognitive concerns following the intervention mediated changes in suicidality at one-month follow-up. Findings are discussed in regard to adjunct interventions for OCD. PMID- 26362690 TI - Long-term Exercise After Pulmonary Rehabilitation (LEAP): Design and rationale of a randomized controlled trial of Tai Chi. AB - BACKGROUND: Persons with chronic obstructive pulmonary disease (COPD) have reduced exercise capacity and levels of physical activity. Supervised, facility based pulmonary rehabilitation programs improve exercise capacity and reduce dyspnea, but novel long-term strategies are needed to maintain the benefits gained. Mind-body modalities such as Tai Chi which combine aerobic activity, coordination of breathing, and cognitive techniques that alleviate the physical inactivity, dyspnea, and anxiety and depression that are the hallmarks of COPD are promising strategies. METHODS/DESIGN: We have designed a randomized controlled study to examine whether Tai Chi will maintain exercise capacity in persons with COPD who have recently completed a supervised pulmonary rehabilitation program, compared to standard care. The primary outcome is 6-min walk test distance at 6 months. Secondary outcomes include health-related quality of life, dyspnea, mood, occurrence of acute exacerbations, engagement in physical activity, exercise self-efficacy, and exercise adherence. Simultaneously, we are conducting a pilot study of group walking. We will enroll 90 persons who will be randomized to one of three arms in a 2:2:1 ratio: Tai Chi, standard care, or group-based walking. DISCUSSION: The Long-term Exercise After Pulmonary Rehabilitation (LEAP) study is a novel and clinically relevant trial. We will enroll a well-characterized cohort of persons with COPD and will comprehensively assess physiological and psychosocial outcomes. Results of this study will provide the evidence base for persons with COPD to engage in Tai Chi as a low cost, long-term modality to sustain physical activity in persons who have completed a standard short-term pulmonary rehabilitation program. TRIAL REGISTRATION: This trial is registered in Clinical Trials.gov, with the ID number of NCT01998724. PMID- 26362693 TI - A nationwide assessment comparing nonelective open with minimally invasive complex colorectal procedures. AB - AIM: The use of minimally invasive colorectal surgery has increased greatly for both benign and malignant disease. Studies evaluating complex procedures have been largely limited to elective indications. We aimed to compare the outcome of a laparoscopic with an open transverse (TC) and total abdominal colectomy (TAC) in the nonelective setting. METHOD: Comparative analysis was made using the Nationwide Inpatient Sample (2008-11) of patients undergoing a nonelective TC or TAC identified by ICD-9-CM procedure codes. The risk-adjusted 30-day outcome was assessed using regression modelling accounting for patient characteristics, comorbidity and surgical procedure. RESULTS: We identified 7261 admissions including 818 laparoscopic and 6443 open procedures. The mean age of the population was 65 +/- 17 years and patients in the laparoscopic group were younger (56 +/- 20 vs. 66 +/- 17 years; P < 0.05). The rate of a single complication was lower in the laparoscopic group (26% vs. 38%; P < 0.01), but this did not remain significant following a logistic regression analysis. Mortality was significantly lower in the laparoscopic group (3.1% vs. 17%; P < 0.01) and this remained true after adjusting for covariates (OR = 0.62; P < 0.05). Laparoscopic cases were associated with a shorter median length of stay (10 vs. 13 days; P < 0.01) and hospital charge ($75,758 vs. $98,833; P < 0.01). CONCLUSION: A nonelective laparoscopic TC or TAC is associated with an equivalent complication rate and lower mortality compared with an open operation. The results should encourage surgeons with the appropriate skills to consider a laparoscopic approach for nonelective pathology requiring a complex colectomy. PMID- 26362694 TI - Adult foreign body aspirations treated for many years with the diagnosis of asthma: report of two cases. AB - While foreign body aspirations are mostly seen in children, they are also observed in adulthood, but in a rare frequency. As it can be asymptomatic for a long time, it can also be confused with many clinical conditions, such as asthma, which can cause chronic cough. Various complications, such as bronchiectasis and pneumonia, can develop in the presence of long-standing aspirated foreign body. In this study, we present two cases one of whom diagnosed with asthma and treated for 30 years, and the other diagnosed with asthma and treated for 10 years. Although no pulmonary complications developed in our first case, bronchiectasis in the right middle lobe developed in our second case. PMID- 26362695 TI - Renal AH Amyloidosis Associated With a Truncated Immunoglobulin Heavy Chain Undetectable by Immunostaining. AB - AH amyloidosis is a rare type of amyloidosis caused by deposition of monoclonal immunoglobulin heavy chain. The key diagnostic feature is positive immunostaining for a single class of immunoglobulin heavy chain. We report a case of AH amyloidosis with immunoglobulin G (IgG) lambda monoclonal gammopathy that was diagnosed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) after immunostaining of renal tissue for immunoglobulin heavy chain gave negative results. The molecular weight of the purified renal amyloid protein was ~11kDa, which was determined by LC-MS/MS analysis to correspond to an amino acid sequence comprising the variable region and a truncated portion of the constant region of IgG heavy chain. The exact same truncated heavy chain was detected by LC-MS/MS of a protein isolated from the patient's serum, suggesting that the truncated serum protein was the precursor of the amyloid protein. Because antibodies to immunoglobulin heavy chain recognize the Fc portion, the large deletion in the constant region could explain the negative results upon immunostaining. Direct protein detection by LC-MS/MS is a powerful aid to diagnose renal AH amyloidosis, particularly when the findings of immunoglobulin staining are inconsistent with the background monoclonal gammopathy. PMID- 26362697 TI - Enhanced gene expression in the brain following intravenous administration of lactoferrin-bearing polypropylenimine dendriplex. AB - The possibility of using gene therapy for the treatment of brain diseases such as brain cancer, Alzheimer's and Parkinson's diseases, is currently hampered by the lack of gene delivery systems able to cross the blood-brain barrier and deliver DNA to the brain following intravenous administration. On the basis that lactoferrin can effectively reach the brain by using specific receptors for crossing the blood-brain barrier, we propose to investigate if a lactoferrin bearing generation 3-diaminobutyric polypropylenimine (DAB) dendrimer would allow the transport of plasmid DNA to the brain after intravenous administration. In this work, we demonstrated that the conjugation of lactoferrin to the dendrimer led to an enhanced DNA uptake by 2.1-fold in bEnd.3 murine brain capillary endothelial cells compared to the unmodified dendriplex in vitro. In vivo, the intravenous administration of lactoferrin-bearing DAB dendriplex resulted in a significantly increased gene expression in the brain, by more than 6.4-fold compared to that of DAB dendriplex, while decreasing gene expression in the lung and the kidneys. Gene expression in the brain was significantly higher than in any other major organs of the body. Lactoferrin-bearing generation 3 polypropylenimine dendrimer is therefore a highly promising delivery system for systemic gene delivery to the brain. PMID- 26362696 TI - GFR Estimation Using beta-Trace Protein and beta2-Microglobulin in CKD. AB - BACKGROUND: beta-Trace protein (BTP) and beta2-microglobulin (B2M) are novel glomerular filtration markers that have stronger associations with adverse outcomes than creatinine. Comparisons of BTP and B2M to creatinine and cystatin C are limited by the absence of rigorously developed glomerular filtration rate (GFR) estimating equations for the novel markers. STUDY DESIGN: Study of diagnostic test accuracy. SETTING & PARTICIPANTS: Pooled database of 3 populations with chronic kidney disease (CKD) with mean measured GFR of 48 mL/min/1.73 m2 (N=3,551; MDRD [Modification of Diet in Renal Disease] Study, AASK [African American Study of Kidney Disease and Hypertension], and CRIC [Chronic Renal Insufficiency Cohort] Study). INDEX TESTS: GFR estimated using creatinine, cystatin C, BTP, or B2M level. REFERENCE TEST: GFR measured as the urinary clearance of iothalamate. RESULTS: For BTP and B2M, coefficients for age, sex, and race were smaller than for creatinine and were similar or smaller than for cystatin C. For B2M, coefficients for sex, age, and race were smaller than for creatinine and were similar (age and race) or smaller (sex) than for cystatin C. The final equations with BTP (BTP, age, and sex) or B2M (B2M alone) were less accurate than either the CKD-EPI (CKD Epidemiology Collaboration) creatinine or cystatin C equations. The combined BTP-B2M equation (BTP and B2M alone) had similar accuracy to the CKD-EPI creatinine or cystatin C equation. The average of the BTP-B2M equation and the CKD-EPI creatinine-cystatin C equation was not more accurate than the CKD-EPI creatinine-cystatin C equation. LIMITATIONS: No external validation population, study population was restricted to CKD, few participants older than 65 years, or nonblack nonwhite race. CONCLUSIONS: BTP and B2M are less influenced by age, sex, and race than creatinine and less influenced by race than cystatin C, but provide less accurate GFR estimates than the CKD-EPI creatinine and cystatin C equations. The CKD-EPI BTP and B2M equation provides a methodological advance for their study as filtration markers and in their associations with risk and adverse outcomes, but further study is required before clinical use. PMID- 26362699 TI - Utilization and impact of a pulsed-xenon ultraviolet room disinfection system and multidisciplinary care team on Clostridium difficile in a long-term acute care facility. AB - Health care-associated transmission of Clostridium difficile has been well documented in long-term acute care facilities. This article reports on 2 interventions aimed at reducing the transmission risk: multidisciplinary care teams and no-touch pulsed-xenon disinfection. C difficile transmission rates were tracked over a 39-month period while these 2 interventions were implemented. After a baseline period of 1 year, multidisciplinary teams were implemented for an additional 1-year period with a focus on reducing C difficile infection. During this time, transmission rates dropped 17% (P = .91). In the following 15 month period, the multidisciplinary teams continued, and pulsed-xenon disinfection was added as an adjunct to manual cleaning of patient rooms and common areas. During this time, transmission rates dropped 57% (P = .02). These results indicate that the combined use of multidisciplinary teams and pulsed xenon disinfection can have a significant impact on C difficile transmission rates in long-term care facilities. PMID- 26362700 TI - Inadequate documentation of urinary tract infection symptoms in the medical chart. AB - We evaluated symptom documentation for 312 inpatients with bacteriuria by comparing information found in the chart with that obtained prospectively from the medical and nursing team caring for the patient. There was only moderate agreement (kappa = 0.55), and only 77% of symptomatic patients had any symptom documented in the chart. PMID- 26362701 TI - The role of CD4 on mechanical properties of live cell membrane. AB - Although much progress has been made in the characterization and identification of CD4 functions, its role in mechanical properties of cell membrane remains largely unknown. Here an atomic force microscopy (AFM) was used to investigate the roles of CD4 in the elasticity of the leukemic human Jurkat (clone E6-1) cell membranes. Analysis of the approach force curves with Hertz model for a completely elastic soft sample measured on the selected CD4+ and CD4- cells showed that CD4+ cell membrane was softer than CD4- one. To confirm that CD4 plays a role in altering cell elasticity, human embryonic kidney 293T cells were transiently transfected with wild type (wt) CD4 plasmid before being used in AFM nanoindentation experiments. The results also demonstrated CD4- membrane was stiffer than CD4+ one suggesting that CD4 integrated into plasma membrane and altered its mechanical properties. The study gives insights into the role of CD4 on cell membrane mechanical characteristics and might be helpful for development of cell biology and medicine. PMID- 26362698 TI - Drug and gene delivery across the blood-brain barrier with focused ultrasound. AB - The blood-brain barrier (BBB) remains one of the most significant limitations to treatments of central nervous system (CNS) disorders including brain tumors, neurodegenerative diseases and psychiatric disorders. It is now well-established that focused ultrasound (FUS) in conjunction with contrast agent microbubbles may be used to non-invasively and temporarily disrupt the BBB, allowing localized delivery of systemically administered therapeutic agents as large as 100nm in size to the CNS. Importantly, recent technological advances now permit FUS application through the intact human skull, obviating the need for invasive and risky surgical procedures. When used in combination with magnetic resonance imaging, FUS may be applied precisely to pre-selected CNS targets. Indeed, FUS devices capable of sub-millimeter precision are currently in several clinical trials. FUS mediated BBB disruption has the potential to fundamentally change how CNS diseases are treated, unlocking potential for combinatorial treatments with nanotechnology, markedly increasing the efficacy of existing therapeutics that otherwise do not cross the BBB effectively, and permitting safe repeated treatments. This article comprehensively reviews recent studies on the targeted delivery of therapeutics into the CNS with FUS and offers perspectives on the future of this technology. PMID- 26362702 TI - Risk factors for cardiovascular disease in rheumatoid arthritis patients from Mato Grosso do Sul. AB - OBJECTIVE: To identify risk factors for cardiovascular disease in patients with Rheumatoid Arthritis (RA). MATERIAL AND METHODS: A descriptive cross-sectional study with 71 patients with established RA. The instruments used were: DAS-28, HAQ and SF-36, and the following parameters were determined: the erythrocyte sedimentation rate, capillary blood glucose; total cholesterol (TC) and its fractions, thyroid hormones, antinuclear antibodies (ANA), rheumatoid factor (RF) and antibodies against citrullinated proteins (ACPAs). Patients were classified into groups HAQ <= 1 (mild dysfunction) and HAQ > 1 (moderate and severe dysfunction) and, according to the HAQ scores, in groups treated with corticosteroids (CS) and without CS. RESULTS: 9 patients were male and 62 female with mean age and duration of disease of 53.45 (+/- 10.7) and 9.9 (+/- 8.6), respectively. RF was positive in 52 (76%), ACPAs in 54 (76.1%) and ANA in 12 (16.9%). Thirty-six patients (50.7%) had systemic hypertension, 9 (12.68%) diabetes mellitus, 16 (22.5%) hypothyroidism, 33 (46.5%) dyslipidemia and 8 (11.27%) were smokers. The results of TC >240 were found in 53.8% for group HAQ >1 (26) and in 24.4% for group HAQ <= 1 (45) (p=0.020). These groups did not differ as to presence of comorbidities or drug treatment. Triglyceride levels >200 for the group with CS (42.4%) versus without CS (18.42%) were significant (p=0.025). CONCLUSION: An association of increased TC and triglycerides with results of HAQ <= 1 and with CS use was noted, reinforcing the importance of screening risk factors associated with cardiovascular disease in RA. PMID- 26362703 TI - Early intervention services in psychosis: from evidence to wide implementation. AB - AIM: Early intervention (EI) in psychosis is a comprehensive and evidence-based approach aimed at detection and treatment of psychotic symptoms in their early stages. This paper presents core features and noteworthy aspects of the evidence basis and limitations of EI, the importance of programme fidelity, challenges for its widespread dissemination and economic perspectives related to it. METHODS: This paper is a narrative review about the evidence supporting EI and the challenges to its widespread dissemination. RESULTS: In spite of evidence of a wide range of benefits, widespread dissemination has been slow, and even currently implemented programmes might be threatened. This reflects in part the shortcomings of mental health care in general, such as low priority for funding, stigma and structural problems. Successful examples of advocacy, mobilization and destigmatization campaigns have overcome these difficulties. CONCLUSIONS: Funding for mental health in general and for EI services appears low relative to need. One key argument for better funding for EI can be found in its favourable cost effectiveness, but not all stakeholders beyond mental health administrators are aware of this. Positive impacts of EI programmes on excess unemployment and tax forgone suggest that social affairs and labour ministries - and not only health ministries - could be more involved in governance of mental health issues; ministries of justice and education are other sector stakeholders than can benefit. Wider dissemination of EI services will probably benefit from better integration of potential funders, promotion of joint targets and shared financial or budgetary incentives. PMID- 26362704 TI - Learning to Appreciate Swiss Cheese and Other Industrial Engineering Concepts. PMID- 26362705 TI - RO-ILS: Radiation Oncology Incident Learning System: A report from the first year of experience. AB - PURPOSE: Incident learning is a critical tool to improve patient safety. The Patient Safety and Quality Improvement Act of 2005 established essential legal protections to allow for the collection and analysis of medical incidents nationwide. METHODS AND MATERIALS: Working with a federally listed patient safety organization (PSO), the American Society for Radiation Oncology and the American Association of Physicists in Medicine established RO-ILS: Radiation Oncology Incident Learning System (RO-ILS). This paper provides an overview of the RO-ILS background, development, structure, and workflow, as well as examples of preliminary data and lessons learned. RO-ILS is actively collecting, analyzing, and reporting patient safety events. RESULTS: As of February 24, 2015, 46 institutions have signed contracts with Clarity PSO, with 33 contracts pending. Of these, 27 sites have entered 739 patient safety events into local database space, with 358 events (48%) pushed to the national database. CONCLUSIONS: To establish an optimal safety culture, radiation oncology departments should establish formal systems for incident learning that include participation in a nationwide incident learning program such as RO-ILS. PMID- 26362706 TI - Can emergent treatments result in more severe errors?: An analysis of a large institutional near-miss incident reporting database. AB - PURPOSE: Emergent radiation treatments may be subject to more errors because of the compressed time frame. Few data exist on the magnitude of this problem or how to guide safety improvement interventions. The purpose of this study is to examine patterns of near-miss events in emergent treatments using a large institutional incident reporting system. METHODS AND MATERIALS: Events in the incident reporting database from February 2012 to October 2013 were reviewed prospectively by a multidisciplinary team to identify emergent treatments. Reports were scored for potential near-miss risk index (NMRI) on a 0 to 4 scale. Workflow steps of where events originated and were detected were analyzed. Events were categorized by use of the causal factor system from the Radiation Oncology Incident Learning System. Mann-Whitney U tests were used to compare mean NMRI score, and Fisher exact tests were performed to compare the proportion of high risk events between emergent and nonemergent treatments and between emergent treatments on weekdays and weekends or holidays. RESULTS: Over the study period, approximately 1600 patients were treated, 190 of them emergently. Seventy-one incident reports were submitted for 55 unique patients. Fewer events were reported for emergent treatments than for nonemergent treatments (0.37 events per new treatment vs 0.86; P < .01). Mean risk index for emergent reports was 1.90 versus 1.48 for nonemergent reports (P < .01). Rate of NMRI 4 was 10% for emergent treatments versus 4% for nonemergent treatments (P < .01). Emergent treatments started on a weekend or holiday had a higher proportion of critical near-miss events than emergent treatments started during the week (37% vs 7.9%, P = .034). CONCLUSIONS: In this study, fewer near-miss incidents were reported per treatment course for emergent treatments. This may be attributable to reporting bias. More importantly, when emergent near misses occur, they are of greater severity. PMID- 26362707 TI - Applying Normal Accident Theory to radiation oncology: Failures are normal but patient harm can be prevented. PMID- 26362708 TI - Accuracy of positron emission tomography may be improved when combined with postcontrast high-resolution computed tomography scanIn Regard to Pepek et al. PMID- 26362709 TI - In Reply to Giron et al. PMID- 26362710 TI - Separating the dosimetric consequences of changing tumor anatomy from positional uncertainty for conventional fractionated lung cancer patients.: In Regard to Grams et al. PMID- 26362711 TI - In Reply to Yartsev and Chen. PMID- 26362712 TI - Embracing Errors in Simulation-Based Training: The Effect of Error Training on Retention and Transfer of Central Venous Catheter Skills. AB - INTRODUCTION: Error management training is an approach that encourages exposure to errors during initial skill acquisition so that learners can be equipped with important error identification, management, and metacognitive skills. The purpose of this study was to determine how an error-focused training program affected performance, retention, and transfer of central venous catheter (CVC) placement skills when compared with traditional training methodologies. METHODS: Surgical interns (N = 30) participated in a 1-hour session featuring an instructional video and practice performing internal jugular (IJ) and subclavian (SC) CVC placement with guided instruction. All interns underwent baseline knowledge and skill assessment for IJ and SC (pretest) CVC placement; watched a "correct-only" (CO) or "correct + error" (CE) instructional video; practiced for 30 minutes; and were posttested on knowledge and IJ and SC CVC placement. Skill retention and transfer (femoral CVC placement) were assessed 30 days later. All skills tests (pretest, posttest, and transfer) were videorecorded and deidentified for evaluation by a single blinded instructor using a validated 17-item checklist. RESULTS: Both the groups exhibited significant improvements (p < 0.001) in knowledge and skills after the 1-hour training program, but the increase of items achieved on the performance checklist did not differ between conditions (CO: IJ Delta = 35%, SC Delta = 29%; CE: IJ Delta = 36%, subclavian Delta = 33%). However, 1 month later, the CO group exhibited significant declines in skill retention on IJ CVC placement (from 68% at posttraining to 44% at day 30; p < 0.05) and SC CVC placement (from 63% at posttraining to 49% at day 30; p < 0.05), whereas the CE group did not have significant decreases in performance. The CE group performed significantly better on femoral CVC placement (i.e., transfer task; 62% vs 38%; p < 0.01) and on 2 of the 3 complication scenarios (p < 0.05) when compared with the CO group. CONCLUSIONS: These data indicate that incorporating error-based activities and discussions into training programs can be beneficial for skill retention and transfer. PMID- 26362713 TI - The best of intentions: patients' intentions to request health care workers cleanse hands before examinations. AB - The Centers for Disease Control and Prevention (CDC) recommends that patients ask health care providers to cleanse their hands in the patients' presence for each examination. This study investigates the utility of the recommendation in light of potential challenges stemming from norms in the provider-patient relationship. In addition, we investigate the role of individual differences that may make such a discussion especially difficult (e.g., interaction anxiety) or seem inappropriate (e.g., authoritarianism). We also seek to identify how well-known predictors of behavioral intentions (i.e., attitudes, subjective norms, efficacy, outcome benefits and costs) affect intentions to perform this specific behavior. In total, 250 hospitalized, postsurgical patients were asked about their own likelihood of following the CDC recommendation. They were also asked to view and respond to video depictions of a doctor and patient interaction that varied the presence of a patient request and a doctor's cleansing. Results of the study suggest the CDC recommendation, without additional considerations, is unlikely to reduce dangers posed by health care worker transmission of infectious disease. PMID- 26362714 TI - Validation of a T1 and T2* leakage correction method based on multiecho dynamic susceptibility contrast MRI using MION as a reference standard. AB - PURPOSE: A combined biophysical- and pharmacokinetic-based method is proposed to separate, quantify, and correct for both T1 and T2* leakage effects using dual echo dynamic susceptibility contrast (DSC) acquisitions to provide more accurate hemodynamic measures, as validated by a reference intravascular contrast agent (CA). THEORY AND METHODS: Dual-echo DSC-MRI data were acquired in two rodent glioma models. The T1 leakage effects were removed and also quantified to subsequently correct for the remaining T2* leakage effects. Pharmacokinetic, biophysical, and combined biophysical and pharmacokinetic models were used to obtain corrected cerebral blood volume (CBV) and cerebral blood flow (CBF), and these were compared with CBV and CBF from an intravascular CA. RESULTS: T1 corrected CBV was significantly overestimated compared with MION CBV, while T1 + T2*-correction yielded CBV values closer to the reference values. The pharmacokinetic and simplified biophysical methods showed similar results and underestimated CBV in tumors exhibiting strong T2* leakage effects. The combined method was effective for correcting T1 and T2* leakage effects across tumor types. CONCLUSION: Correcting for both T1 and T2* leakage effects yielded more accurate measures of CBV. The combined correction method yields more reliable CBV measures than either correction method alone, but for certain brain tumor types (e.g., gliomas), the simplified biophysical method may provide a robust and computationally efficient alternative. Magn Reson Med 76:613-625, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26362716 TI - miR-506 Inhibits Epithelial-to-Mesenchymal Transition and Angiogenesis in Gastric Cancer. AB - Gastric cancer is one of the most common malignancies in developing countries. We examined the possible role of miR-506 in gastric cancer, investigated its associations with the clinical outcomes of gastric cancer patients, and explored its potential role in angiogenesis and the metastasis of gastric cancer cells. We found that miR-506 expression was a useful marker for stratifying patients from early to advanced clinical stages and for overall survival prediction. miR-506 overexpression inhibited the epithelial-to-mesenchymal transition of gastric cancer cells; however, depletion of miR-506 promoted it. In addition, miR-506 suppressed gastric cancer angiogenesis and was associated with decreased matrix metalloproteinase-9 expression. We also found that ETS1 was a miR-506 target, and it was expressed in 71.10% of gastric cancer tissue samples. Moreover, ETS1 expression was associated with matrix metalloproteinase-9 expression (P < 0.001). In conclusion, miR-506 was identified as an ETS1 targeting suppressor of metastatic invasion and angiogenesis in gastric cancer. PMID- 26362717 TI - Insulin-Like Growth Factor-1 Contributes to Mucosal Repair by beta-Arrestin2 Mediated Extracellular Signal-Related Kinase Signaling in Experimental Colitis. AB - Insulin-like growth factor-1 (IGF-1) possesses the ability to attenuate intestinal damage and promote mucosal repair of colitis. beta-Arrestins, as the scaffolding proteins of G protein-coupled receptors or non-G protein-coupled receptors signaling, can be involved in IGF-1-mediated signaling pathways. However, the interaction of IGF-1 and beta-arrestin2 in the mucosal repair of experimental colitis remains unexplored. Ulcerative colitis was induced in beta arrestin2 wild-type mice and beta-arrestin2 knockout littermates by using 3% dextran sulfate sodium for 5 days, followed by regular water consumption for 1, 2, 3, and 4 weeks to analyze the mucosal repair from experimental colitis. Disease activity index and histologic score analyses were performed. Apoptosis and proliferation were assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling and Ki-67 staining, respectively. The expressions of beta arrestin2, phospho (p)-IGF-1R, and p-extracellular signal-regulated kinase (ERK)1/2 were examined. Furthermore, beta-arrestin2 was overexpressed or altered in HCT116 cells by transfection before IGF-1 treatment in vitro. IGF-1 and beta arrestin2 expression was up-regulated in the repairing phase of experimental colitis. Targeted deletion of beta-arrestin2 delayed the repair of colitis by inhibiting cell proliferation without affecting the levels of IGF-1 and p-IGF-1R. The beta-arrestin2/ERK signaling pathway was involved in IGF-1-mediated mucosal repair through promoting epithelial cell and goblet cell regeneration from experimental colitis. These results indicate that IGF-1 contributes to the mucosal repair by beta-arrestin2-mediated ERK signaling in experimental colitis. PMID- 26362719 TI - Imperceptible signs: remnants of magnetisme in scientific discourses on hypnotism in late nineteenth-century France. AB - In 1880s France, hypnotism enjoyed unique medico-scientific legitimacy. This was in striking contrast to preceding decades when its precursor, magnetisme animal, was rejected by the medical/academic establishment as a disreputable, supernaturally tinged practice. Did the legitimation of hypnotism result from researchers repudiating any reference to the wondrous? Or did strands of magnetic thinking persist? This article interrogates the relations among hypnotism, magnetisme, and the domain of the wondrous through close analysis of scientific texts on hypnotism. In question is the notion that somnambulist subjects possessed hyperacute senses, enabling them to perceive usually imperceptible signs, and thus inadvertently to denature researchers' experiments (a phenomenon known as unconscious suggestion). The article explores researchers' uncritical and unanimous acceptance of these ideas, arguing that they originate in a holdover from magnetisme. This complicates our understanding of the continuities and discontinuities between science and a precursor "pseudo-science," and, more narrowly, of the notorious Salpetriere-Nancy "battle" over hypnotism. PMID- 26362720 TI - Influence of dual-task on sit-to-stand-to-sit postural control in Parkinson's disease. AB - Postural control deficits are the most disabling aspects of Parkinson's disease (PD), resulting in decreased mobility and functional independence. The aim of this study was to assess the postural control stability, revealed by variables based on the centre of pressure (CoP), in individuals with PD while performing a sit-to-stand-to-sit sequence under single- and dual-task conditions. An observational, analytical and cross-sectional study was performed. The sample consisted of 9 individuals with PD and 9 healthy controls. A force platform was used to measure the CoP displacement and velocity during the sit-to-stand-to-sit sequence. The results were statistically analysed. Individuals with PD required greater durations for the sit-to-stand-to-sit sequence than the controls (p < 0.05). The anteroposterior and mediolateral CoP displacement were higher in the individuals with PD (p < 0.05). However, only the anteroposterior CoP velocity in the stand-to-sit phase (p = 0.006) was lower in the same individuals. Comparing the single- and dual-task conditions in both groups, the duration, the anteroposterior CoP displacement and velocity were higher in the dual-task condition (p < 0.05). The individuals with PD presented reduced postural control stability during the sit-to-stand-to-sit sequence, especially when under the dual task condition. These individuals have deficits not only in motor performance, but also in cognitive performance when performing the sit-to-stand-to-sit sequence in their daily life tasks. Moreover, both deficits tend to be intensified when two tasks are performed simultaneously. PMID- 26362718 TI - Jak2-Stat5a/b Signaling Induces Epithelial-to-Mesenchymal Transition and Stem Like Cell Properties in Prostate Cancer. AB - Active Stat5a/b predicts early recurrence and disease-specific death in prostate cancer (PC), which both typically are caused by development of metastatic disease. Herein, we demonstrate that Stat5a/b induces epithelial-to-mesenchymal transition (EMT) of PC cells, as shown by Stat5a/b regulation of EMT marker expression (Twist1, E-cadherin, N-cadherin, vimentin, and fibronectin) in PC cell lines, xenograft tumors in vivo, and patient-derived PCs ex vivo using organ explant cultures. Jak2-Stat5a/b signaling induced functional end points of EMT as well, indicated by disruption of epithelial cell monolayers and increased migration and adhesion of PC cells to fibronectin. Knockdown of Twist1 suppressed Jak2-Stat5a/b-induced EMT properties of PC cells, which were rescued by re introduction of Twist1, indicating that Twist1 mediates Stat5a/b-induced EMT in PC cells. While promoting EMT, Jak2-Stat5a/b signaling induced stem-like properties in PC cells, such as sphere formation and expression of cancer stem cell markers, including BMI1. Mechanistically, both Twist1 and BMI1 were critical for Stat5a/b induction of stem-like features, because genetic knockdown of Twist1 suppressed Stat5a/b-induced BMI1 expression and sphere formation in stem cell culture conditions, which were rescued by re-introduction of BMI1. By using human prolactin knock-in mice, we demonstrate that prolactin-Stat5a/b signaling promoted metastases formation of PC cells in vivo. In conclusion, our data support the concept that Jak2-Stat5a/b signaling promotes metastatic progression of PC by inducing EMT and stem cell properties in PC cells. PMID- 26362721 TI - Automatic detection of selective arterial devices for advanced visualization during abdominal aortic aneurysm endovascular repair. AB - Here we address the automatic segmentation of endovascular devices used in the endovascular repair (EVAR) of abdominal aortic aneurysms (AAA) that deform vascular tissues. Using this approach, the vascular structure is automatically reshaped solving the issue of misregistration observed on 2D/3D image fusion for EVAR guidance. The endovascular devices we considered are the graduated pigtail catheter (PC) used for contrast injection and the stent-graft delivery device (DD). The segmentation of the DD was enhanced using an asymmetric Frangi filter. The segmented geometries were then analysed using their specific features to remove artefacts. The radiopaque markers of the PC were enhanced using a fusion of Hessian and newly introduced gradient norm shift filters. Extensive experiments were performed using a database of images taken during 28 AAA-EVAR interventions. This dataset was divided into two parts: the first half was used to optimize parameters and the second to compile performances using optimal values obtained. The radiopaque markers of the PC were detected with a sensitivity of 88.3% and a positive predictive value (PPV) of 96%. The PC can therefore be positioned with a majority of its markers localized while the artefacts were all located inside the vessel lumen. The major parts of the DD, the dilatator tip and the pusher surfaces, were detected accurately with a sensitivity of 85.9% and a PPV of 88.7%. The less visible part of the DD, the stent enclosed within the sheath, was segmented with a sensitivity of 63.4% because the radiopacity of this region is low and uneven. The centreline of the DD in this stent region was alternatively traced within a 0.74 mm mean error. The automatic segmentation of endovascular devices during EVAR is feasible and accurate; it could be useful to perform elastic registration of the vascular lumen during endovascular repair. PMID- 26362722 TI - Dynamic tumor-tracking radiotherapy with real-time monitoring for liver tumors using a gimbal mounted linac. AB - PURPOSE: Dynamic tumor-tracking stereotactic body radiotherapy (DTT-SBRT) for liver tumors with real-time monitoring was carried out using a gimbal-mounted linear accelerator and the efficacy of the system was determined. In addition, four-dimensional (4D) dose distribution, tumor-tracking accuracy, and tumor marker positional variations were evaluated. MATERIALS AND METHODS: A fiducial marker was implanted near the tumor prior to treatment planning. The prescription dose at the isocenter was 48-60 Gy, delivered in four or eight fractions. The 4D dose distributions were calculated with a Monte Carlo method and compared to the static SBRT plan. The intrafractional errors between the predicted target positions and the actual target positions were calculated. RESULTS: Eleven lesions from ten patients were treated successfully. DTT-SBRT allowed an average 16% reduction in the mean liver dose compared to static SBRT, without altering the target dose. The average 95th percentiles of the intrafractional prediction errors were 1.1, 2.3, and 1.7 mm in the left-right, cranio-caudal, and anterior posterior directions, respectively. After a median follow-up of 11 months, the local control rate was 90%. CONCLUSIONS: Our early experience demonstrated the dose reductions in normal tissues and high accuracy in tumor tracking, with good local control using DTT-SBRT with real-time monitoring in the treatment of liver tumors. PMID- 26362723 TI - Phase I dose-escalation study of stereotactic body radiotherapy (SBRT) for poor surgical candidates with localized renal cell carcinoma. AB - PURPOSE: To evaluate the tolerability of escalating doses of stereotactic body radiotherapy (SBRT) for primary treatment of localized renal cell carcinoma (RCC) in poor surgical candidates. PATIENTS AND METHODS: Eligible patients included those with clinically staged radiographic and or pathologically confirmed RCC who had not undergone previous abdominal or pelvic radiotherapy. All patients had comorbid medical conditions which precluded surgery. Median (range) patient age was 77.6years (range 59-89) years and all patients had Karnofsky Performance Status of ?60. Median tumor volume was 57.9cm(3) (range 13.8-174.7cm(3)). Dose limiting toxicity (DLT) was defined as grade 3 or worse gastrointestinal/genitourinary toxicity by Common Terminology Criteria of Adverse Events (version 4). Tumor response was assessed by imaging results using Response Evaluation Criteria In Solid Tumors (RECIST) measurement and percutaneous biopsy. RESULTS: A total of 19 patients (13 men and 6 women) were treated on protocol from June 2006 through August 2011. Groups of 3-6 patients received 24, 32, 40, and 48Gy in 4 fractions. Median (range) follow-up was 13. 7months (5.9 34.7months). For possibly treatment-related acute toxicities, one patient developed grade 2 fatigue and one developed grade 4 duodenal ulcer. For possibly treatment-related late toxicities, 2 patients experienced grade 3 renal toxicity (worsening chronic kidney disease), one reported grade 2 urinary incontinence and one developed grade 4 duodenal ulcer. Among the 15 patients with evaluable response, 3 and 12 had partial response and stable disease, respectively, utilizing RECIST criteria. Among the 11 patients who had post-SBRT biopsy, only one (9%) was negative on first biopsy and an additional one (9%) turned negative without further therapy on second biopsy. CONCLUSIONS: Dose escalation to 48Gy in 4 fractions has been achieved successfully without dose-limiting toxicities. A planned extension of this phase I trial is currently underway treating patients to 60Gy in 3 fractions to further evaluate this experimental therapy. PMID- 26362724 TI - Amyloid beta: Walking on the dark side of the moon. AB - For some decades, amyloid beta (Abeta) has only been considered as a cytotoxic peptide, putative cause and marker of Alzheimer's disease (AD). Today, however, a considerable amount of evidence goes against the classical amyloid hypothesis and illustrates a new picture in which the Abeta loss of function, rather than its accumulation, has a pathogenic role in AD. In this concise review, we summarize some highlights of a collection of research pointing to the physiological function of Abeta and its role in the mechanisms of memory formation. PMID- 26362725 TI - Non-coding RNA-mediated epigenetic regulation of liver fibrosis. AB - Hepatic stellate cells (HSC) activation plays a key role in liver fibrosis. Numerous studies have indicated that non-coding RNAs (ncRNAs) control liver fibrosis and fibroblasts proliferation. Greater knowledge of the role of the ncRNAs-mediated epigenetic mechanism in liver fibrosis could improve understanding of the liver fibrosis pathogenesis. The aim of this review is to describe the present knowledge about the ncRNAs significantly participating in liver fibrosis and HSC activation, and look ahead on new perspectives of ncRNAs mediated epigenetic mechanism research. Moreover, we will discuss examples of non coding RNAs that interact with histone modification or DNA methylation to regulate gene expression in liver fibrosis. Diverse classes of ncRNAs, ranging from microRNAs (miRs) to long non-coding RNAs (LncRNAs), have emerged as key regulators of several important aspects of function, including cell proliferation, activation, etc. In addition, recent advances suggest the important role of ncRNAs transcripts in epigenetic gene regulation. Targeting the miRs and LncRNAs can be a promising direction in liver fibrosis treatment. We discuss new perspectives of miRs and LncRNAs in liver fibrosis and HSC activation, mainly including interaction with histone modification or DNA methylation to regulate gene expression. These epigenetic mechanisms form powerful ncRNAs surveillance systems that may represent new targets for liver fibrosis therapeutic intervention. PMID- 26362726 TI - First-trimester biochemical markers of placentation in screening for gestational diabetes mellitus. AB - OBJECTIVE: To investigate whether first-trimester biochemical markers of placentation, including pregnancy-associated plasma protein-A (PAPP-A) and placental growth factor (PLGF), are altered in women that subsequently develop gestational diabetes mellitus (GDM) and to examine their potential value in improving the performance of screening for GDM by maternal characteristics and medical history. METHODS: The study population of 31,225 singleton pregnancies, including 787 cases that developed GDM, was drawn from women undergoing routine prospective screening for pregnancy complications at 11-13 weeks' gestation. Maternal serum PAPP-A and PLGF were measured and the levels were expressed as multiples of the median (MoM) after adjustment for maternal characteristics and medical history. The performance of screening for GDM by maternal factors and MoM values of PAPP-A and PLGF was evaluated by receiver operating characteristic (ROC) curves. RESULTS: In the GDM group, compared to the unaffected group, the median PAPP-A was reduced (0.949, 95% CI 0.913-0.987 MoM) (p=0.0009) and median PLGF was increased (1.053, 95% CI 1.023-1.083 MoM) (p=0.004). The performance of screening for GDM by maternal factors was not improved by the addition of PAPP-A and/or PLGF. CONCLUSIONS: First trimester maternal serum PAPP-A and PLGF are not useful in screening for GDM. PMID- 26362727 TI - Increased expression of ATP-binding cassette transporter A1 (ABCA1) as a possible mechanism for the protective effect of cilostazol against hepatic steatosis. AB - OBJECTIVE: Cilostazol, a phosphodiesterase 3, has been widely used in patients with arterial disease and is known to have additional beneficial effects on dyslipidemia. However, the effect of cilostazol on hepatic steatosis has not been fully elucidated. We investigated the effect of cilostazol on hepatic ABCA1 expression and hepatic steatosis in diet-induced obesity mice model. METHODS: Hepatic ABCA1 expression and lipid accumulation were analyzed in HepG2 cell lines treated with cilostazol. Male C57BL/6 mice were randomly divided into three groups: (1) fed normal chow diet with vehicle; (2) fed high-fat diet (HFD) with vehicle; (3) fed HFD with cilostazol. Cilostazol (30 mg/kg) was orally administered once daily for 9 weeks. RESULTS: Cilostazol significantly enhanced ABCA1 expression and restored ABCA1 expression reduced by palmitate in HepG2 cells. Cilostazol treatment ameliorated lipid accumulation induced by palmitate, and this effect was diminished when ABCA1 or LRP1 was silenced by small interference RNA. After silencing of LRP1, ABCA1 expression was decreased in HepG2 cells. Cilostazol significantly enhanced hepatic ABCA1 expression and decreased hepatic fat in HFD-fed mice. Hepatic expression of cleaved caspase-3 and PARP1 was also decreased in HFD-fed mice treated with cilostazol. CONCLUSIONS: Cilostazol ameliorated hepatic steatosis and increased ABCA1 expression in the hepatocytes. Enhancing ABCA1 expression with cilostazol represents a potential therapeutic avenue for treatment of hepatic steatosis. PMID- 26362728 TI - Weight regaining: From statistics and behaviors to physiology and metabolism. AB - Achieving maintenance of weight loss is crucial to combat obesity. However, most individuals tend to regain weight. Data from successful maintainers show that they remain vigilant and constantly apply techniques to oppose the course of regaining. On the other hand, current advances in obesity research show that the reduced obese state is a state of altered physiology in terms of energy balance. This review describes the physiological adaptations occurring after weight loss that predispose to regaining. Specifically, changes regarding body composition, hormonal background, energy expenditure and control of food intake are discussed. Moreover, metabolites that can act as regain predictors and dietary techniques to oppose regaining are presented. PMID- 26362729 TI - Similarities in the surface area/volume ratio in the fibers of the recurrent laryngeal nerve can explain the symmetry in the vocal fold mobility? AB - We demonstrate in this paper that although there are statistical differences for all morphometric data [axon length, axon diameter, myelinated fiber diameter and degree of the myelination (g-Ratio)] between the fibers of recurrent laryngeal nerve right and left, the surface area/volume ratio in the fibers of both nerves is exactly the same (1/1.7). Thereby, this paper presents the hypothesis that this similarity between the nerves can actually trigger a considerable synchrony in mobility of the intrinsic muscles of the larynx that control of the vocal folds. PMID- 26362730 TI - Immobilised UGT1A9 may be used to treat paracetamol overdose. PMID- 26362731 TI - Pulse wave myelopathy: An update of an hypothesis highlighting the similarities between syringomyelia and normal pressure hydrocephalus. AB - Most hypotheses trying to explain the pathophysiology of idiopathic syringomyelia involve mechanisms whereby CSF is pumped against a pressure gradient, from the subarachnoid space into the cord parenchyma. On review, these theories have universally failed to explain the disease process. A few papers have suggested that the syrinx fluid may originate from the cord capillary bed itself. However, in these papers, the fluid is said to accumulate due to impaired fluid drainage out of the cord. Again, there is little evidence to substantiate this. This proffered hypothesis looks at the problem from the perspective that syringomyelia and normal pressure hydrocephalus are almost identical in their manifestations but only differ in their site of effect within the neuraxis. It is suggested that the primary trigger for syringomyelia is a reduction in the compliance of the veins draining the spinal cord. This reduces the efficiency of the pulse wave dampening, occurring within the cord parenchyma, increasing arteriolar and capillary pulse pressure. The increased capillary pulse pressure opens the blood spinal cord barrier due to a direct effect upon the wall integrity and interstitial fluid accumulates due to an increased secretion rate. An increase in arteriolar pulse pressure increases the kinetic energy within the cord parenchyma and this disrupts the cytoarchitecture allowing the fluid to accumulate into small cystic regions in the cord. With time the cystic regions coalesce to form one large cavity which continues to increase in size due to the ongoing interstitial fluid secretion and the hyperdynamic cord vasculature. PMID- 26362732 TI - Th17 cytokines regulate osteoclastogenesis in rheumatoid arthritis. AB - This study determined the effect of type 17 helper T-cell (Th17) cytokines on osteoclastogenesis in rheumatoid arthritis (RA). The expression of IL-17 and receptor activator of NF-kappaB ligand (RANKL) was determined in synovial tissue, fibroblast-like synoviocytes (FLSs), and synovial fluids of RA patients using immunostaining and enzyme-linked immunosorbent assay. Th17 cytokine-induced RANKL expression was studied in RA FLS by using real-time PCR, luciferase activity assays, and Western blot analysis. Human peripheral blood monocytes were cultured with macrophage colony-stimulating factor and Th17 cytokines, after which osteoclastogenesis was evaluated by counting the number of tartrate-resistant acid phosphatase-positive multinucleated cells. Osteoclastogenesis was also evaluated after monocytes were co-cultured with IL-17-prestimulated FLS. There was significant correlation between RANKL and IL-17 levels in RA synovial fluid. IL-17, IL-21, and IL-22 increased the expression of Rankl mRNA in RA FLS, and the IL-17-induced RANKL expression decreased by the inhibition of Act1, tumor necrosis factor receptor-associated factor 6, NF-kappaB, and activator protein-1. Th17 cytokines and IL-17-prestimulated FLS induced osteoclastogenesis from monocytes in the absence of exogenous RANKL. The osteoclastic effect was reduced by inhibition of tumor necrosis factor-alpha. Th17 cytokines have a dual effect on osteoclastogenesis in RA: direct induction of osteoclastogenesis from monocytes and up-regulation of RANKL production in RA FLS. This Th17 cytokine/RANKL axis could be a potential therapeutic target for bone destruction in RA. PMID- 26362733 TI - Microglial keratan sulfate epitope elicits in central nervous tissues of transgenic model mice and patients with amyotrophic lateral sclerosis. AB - The functional role of 5D4 antibody-reactive keratan sulfate (KS) in the pathogenesis of neurodegenerative diseases is unknown. We therefore studied the expression of 5D4-reactive KS in amyotrophic lateral sclerosis (ALS), a motor neuron-degenerative disease, with the use of SOD1(G93A) ALS model mice and patients with ALS. Histochemical and immunoelectron microscopic characterizations showed that the 5D4-reactive KS is expressed in Mac2/galectin-3-positive activated or proliferating microglia of SOD1(G93A) ALS model mice at disease end stage and that the KS is an O-linked glycan modified with sialic acid and fucose, which was thus far shown to exist in cartilage. Intriguingly, microglial KS was detected in the spinal cord and brainstem but not in the cerebral cortex of SOD1(G93A) mice. We found that KSGal6ST, a galactose-6-sulfotransferase, is required for biosynthesis of the microglial 5D4-reactive KS by generating SOD1(G93A)/KSGal6ST(-/-) mice. The requirement of GlcNAc6ST1 for this synthesis was corroborated by analyzing SOD1(G93A)/GlcNAc6ST1(-/-) mice. These results indicate that both galactose-6- and N acteylglucosamine-6-sulfated KS elicited in the spinal cord and brainstem are associated with the degeneration of spinal and bulbar lower motor neurons in ALS pathology and may play a role in disease progression via microglial activation and proliferation. PMID- 26362734 TI - What's in an item? Predicting social outcomes in schizophrenia spectrum disorders from the PANSS item "Poor Rapport". PMID- 26362735 TI - The impact of Herpes simplex virus type 1 on cognitive impairments in young, healthy individuals - A historical prospective study. AB - Herpes simplex virus (HSV) is a highly prevalent neurotropic virus. Although on the whole, chronic, latent or persistent infection is considered to be relatively benign, HSV infections can cause cognitive impairment during and after acute encephalitis. Some studies have documented cognitive impairment in exposed persons that is untraceable to encephalitis. Most studies have focused on these impairments in the mentally ill, mostly among individuals with schizophrenia, and only recently have studies begun to examine the impact of HSV infection on the cognition of healthy individuals. Subjects were a representative, random sample of 612 soldiers before active duty in the Israeli military (Israeli defense force - IDF), 62.2% HSV positive (n=381) and 38.8% HSV negative (n=231). Cognitive functioning and language abilities were compared between these groups, controlling for years of education, immigration status, and gender. Compared to soldiers who were sero-negative, soldiers who were sero-positive for HSV had significantly lower IQ scores (IQ=97.96, SD=15.19 vs IQ=103.23, SD=14.23; p<=0.001, effect size (ES)=0.2), and significantly lower Hebrew language scores (ES=0.1, p<=0.01). The results remained significant after removing subjects with mild depression, anxiety or personality disorders. Although we could not control for socio-economic status directly, our findings indicate that infection with HSV 1 is associated with reduced cognitive functioning in healthy individuals. This finding adds to the growing number of studies in the schizophrenia literature and indicates that many research findings seemingly characteristic of schizophrenia are related to the association between HSV exposure and cognitive functioning in general, and are not illness specific. PMID- 26362736 TI - Reward-dependent modulation of working memory is associated with negative symptoms in schizophrenia. AB - The negative symptoms of schizophrenia have been associated with altered neural activity during both reward processing and cognitive processing. Even though increasing evidence suggests a strong interaction between these two domains, it has not been studied in relation to negative symptoms. To elucidate neural mechanisms of the reward-cognition interaction, we applied a letter variant of the n-back working memory task and varied the financial incentives for performance. In the interaction contrast, we found a significantly activated cluster in the rostral anterior cingulate cortex (ACC), the middle frontal gyrus, and the bilateral superior frontal gyrus. The interaction did not differ significantly between the patient group and a healthy control group, suggesting that patients with schizophrenia are on average able to integrate reward information and utilize this information to maximize cognitive performance. However within the patient group, we found a significant inverse correlation of ACC activity with the factor diminished expression. This finding is consistent with the model that a lack of available cognitive resources leads to diminished expression. We therefore argue that patients with diminished expression have difficulties in recruiting additional cognitive resources (as implemented in the ACC) in response to an anticipated reward. Due to this lack of cognitive resources, less processing capacity is available for effective expression, resulting in diminished expressive behavior. PMID- 26362737 TI - Infections and musculoskeletal conditions. Preface. PMID- 26362738 TI - The association between rheumatoid arthritis and periodontitis. AB - The relationship between rheumatoid arthritis and poor oral health has been recognised for many decades. The association between periodontal infection and the risk of developing RA has been the subject of epidemiological, clinical and basic science research in recent times. Converging and reproducible evidence now makes a clear case for the role of specific periodontal infective pathogens in initiating, amplifying and perpetuating rheumatoid arthritis. The unique enzymatic properties of the periodontal pathogen Porphyromonas gingivalis and its contribution to the burden of citrullinated peptides is now well established. The impact of localized infection such as periodontitis in shaping specific anti citrullinated peptide immune responses highlights a key area for treatment, prevention and risk assessment in rheumatoid arthritis. PMID- 26362739 TI - The intestinal microbiome in human disease and how it relates to arthritis and spondyloarthritis. AB - Humans and microbes have developed a symbiotic relationship over time, and alterations in this symbiotic relationship have been linked to several immune mediated diseases such as inflammatory bowel disease, type 1 diabetes and spondyloarthropathies. Improvements in sequencing technologies, coupled with a renaissance in 16S rRNA gene based community profiling, have enabled the characterization of microbiomes throughout the body including the gut. Improved characterization and understanding of the human gut microbiome means the gut flora is progressively being explored as a target for novel therapies including probiotics and faecal microbiota transplants. These innovative therapies are increasingly used for patients with debilitating conditions where conventional treatments have failed. This review discusses the current understanding of the interplay between host genetics and the gut microbiome in the pathogenesis of spondyloarthropathies, and how this may relate to potential therapies for these conditions. PMID- 26362740 TI - Role of genetics in infection-associated arthritis. AB - Genetic discoveries in arthritis and their associated biological pathways spanning the innate and adaptive immune system demonstrate the strong association between susceptibility to arthritis and control of exogenous organisms. The canonical theory of the aetiology of immune-mediated arthritis and other immune mediated diseases is that the introduction of exogenous antigenic stimuli to a genetically susceptible host sets up the environment for an abnormal immune response manifesting as disease. A disruption in host-microbe homeostasis driven by disease-associated genetic variants could ultimately provide the source of exogenous antigen triggering disease development. We discuss genetic variants impacting the innate and adaptive arms of the immune system and their relationship to microbial control and arthritic disease. We go on to consider the evidence for a relationship between HLA-B27, infection and arthritis, and then emerging evidence for an interaction between microbiota and rheumatoid arthritis. PMID- 26362741 TI - Vasculitis related to viral and other microbial agents. AB - Vasculitis due to infection may occur as a consequence of the inflammation of vessel walls due to direct or contiguous infection, type II or immune complex mediated reaction, cell-mediated hypersensitivity, or inflammation due to immune dysregulation triggered by bacterial toxin and/or superantigen production. As immunosuppressive therapy administered in the absence of antimicrobial therapy may increase morbidity and fail to effect the resolution of infection-associated vascular inflammation, it is important to consider infectious entities as potential inciting factors in vasculitis syndromes. The causality between infection and vasculitis has been established in hepatitis B-associated polyarteritis nodosa (HBV-PAN) and hepatitis C-associated (cryoglobulinemic) vasculitis (HCV-CV). The review summarizes the recent literature on the pathophysiological mechanisms and the approaches to the management of HBV-PAN and HCV-CV. Roles of other viral and microbial infections, which either manifest as vasculitic syndromes or are implicated in the pathogenesis of primary vasculitides, are also discussed. PMID- 26362743 TI - Arthropod-borne arthritides. AB - Infections with several types of viral and bacterial pathogens are able to cause arthritic disease. Arthropod vectors such as ticks and mosquitoes transmit a number of these arthritis-causing pathogens, and as these vectors increase their global distribution, so too do the diseases they spread. The typical clinical manifestations of infectious arthritis are often similar in presentation to rheumatoid arthritis. Hence, care needs to be taken in the diagnoses and management of these conditions. Additionally, clinical reports suggest that prolonged arthropathies may result from infection, highlighting the need for careful clinical management and further research into underlying disease mechanisms. PMID- 26362744 TI - Septic arthritis in immunocompetent and immunosuppressed hosts. AB - Septic arthritis has long been considered an orthopedic emergency. Historically, Neisseria gonorrhoeae and Staphylococcus aureus have been the most common causes of septic arthritis worldwide but in the modern era of biological therapy and extensive use of prosthetic joint replacements, the spectrum of microbiological causes of septic arthritis has widened considerably. There are also new approaches to diagnosis but therapy remains a challenge, with a need for careful consideration of a combined medical and surgical approach in most cases. PMID- 26362742 TI - Evolving spectrum of HIV-associated rheumatic syndromes. AB - At the end of 2013, 35 million people worldwide were infected with HIV. The prognosis of HIV has been transformed by combination antiretroviral therapy (cART). Providing compliance is good, the use of cART has normalised the life expectancy of HIV-infected people leading to a growing population of people with chronic infection. Management of HIV patients has therefore needed to adapt in order to not only control viral activity but also manage long-term complications of HIV and cART. Rheumatological manifestations of HIV were first described in 1989. Since then, there have been case reports, case series and epidemiological studies describing different clinical manifestations of HIV in the musculoskeletal system. This review will encompass musculoskeletal pain, fibromyalgia, systemic lupus erythematosus (SLE) and inflammatory arthritis in HIV. We will aim to report on the prevalence of these conditions and the risk factors, explore the impact of the virus on the clinical presentations and discuss implications for diagnosis and management. PMID- 26362745 TI - Risk of infection with biologic antirheumatic therapies in patients with rheumatoid arthritis. AB - There are currently 10 licensed biologic therapies for the treatment of rheumatoid arthritis in 2014. In this article, we review the risk of serious infection (SI) for biologic therapies. This risk has been closely studied over the last 15 years within randomised controlled trials, long-term extension studies and observational drug registers, especially for the first three antitumour necrosis factor (TNF) drugs, namely infliximab, etanercept and adalimumab. The risk of SI with the newer biologics rituximab, tocilizumab, abatacept and tofacitinib is also reviewed, although further data from long-term observational studies are awaited. Beyond all-site SI, we review the risk of tuberculosis, other opportunistic infections and herpes zoster, and the effect of screening on TB rates. Lastly, we review emerging opportunities for stratifying the risk. Patients can be risk-stratified based on both modifiable and non modifiable patient characteristics such as age, co-morbidity, glucocorticoid use, functional status and recent previous SI. PMID- 26362746 TI - Role of vaccinations and prophylaxis in rheumatic diseases. AB - Targeted strategies for reducing the increased risk of infection in patients with autoimmune rheumatic diseases include vaccinations as well as antibiotic prophylaxis in selected patients. However, there are still issues under debate: Is vaccination in patients with rheumatic diseases immunogenic? Is it safe? What is the impact of immunosuppressive drugs on vaccine immunogenicity and safety? Does vaccination cause disease flares? In which cases is prophylaxis against Pneumocystis jirovecii required? This review addresses these important questions to which clinicians and researchers still do not have definite answers. The first part includes immunization recommendations and reviews current data on vaccine efficacy and safety in patients with rheumatic diseases. The second part discusses prophylaxis for Pneumocystis pneumonia. PMID- 26362748 TI - Are some diets "mass murder"? PMID- 26362747 TI - Treatment considerations in patients with concomitant viral infection and autoimmune rheumatic diseases. AB - Widespread use of immunosuppressive drugs, both conventional disease-modifying antirheumatic drugs (cDMARDs) and biologic disease-modifying antirheumatic drugs (bDMARDs), in autoimmune rheumatic diseases (ARDs) has been found to be associated with the reactivation of underlying latent viruses. The clinical features of virus reactivation can sometimes mimic flare of the underlying ARDs. The correct diagnosis and management of such reactivation is crucial, as increasing the dose of immunosuppressive drugs to treat a presumed flare of underlying ARDs would probably be of no benefit, and it could exert a detrimental effect on the host. This review focused on the effects of immunosuppressive drugs on underlying chronic viral infections, particularly hepatitis B virus, hepatitis C virus, human immunodeficiency virus, varicella zoster virus, Epstein-Barr virus, cytomegalovirus, John Cunningham (JC) virus, Kaposi sarcoma-associated herpesvirus, and human papillomavirus in patients with ARDs. It also covered the effect of interferon-alpha, which is used to treat chronic hepatitis infection, and the induction of autoimmunity. PMID- 26362749 TI - Olopatadine hydrochloride suppresses hot flashes induced by topical treatment with tacrolimus ointment in rats. AB - Tacrolimus ointment is prescribed for patients with atopic dermatitis, although it is known to cause transient burning sensations and hot flashes in the applied skin. The aim of this study was to evaluate the effects of olopatadine hydrochloride (olopatadine), an antiallergic agent with a histamine H1 receptor (H1R) antagonistic activity, on the incidence of hot flashes induced by topical treatment with tacrolimus ointment in rats. Consequently, the skin temperature was increased by the topical application of tacrolimus ointment in rats, and the rise in skin temperature was inhibited by pretreatment with olopatadine in a dose dependent manner. Inhibitory effect of olopatadine on tacrolimus-induced skin temperature elevation was significantly more potent than that of cetirizine hydrochloride, other antiallergic agent with H1R antagonistic activity, at doses in which both agents exhibit comparable H1R antagonistic activity in rats. These results suggest that H1R antagonistic activity-independent mechanism contribute to the inhibitory effect of olopatadine on tacrolimus-induced skin temperature elevation. Olopatadine also significantly inhibited increases in vascular permeability and nerve growth factor production in the skin induced by topical tacrolimus treatment. Thus, the onset of hot flashes in rats is quantitatively determined by measuring the skin temperature and olopatadine attenuates hot flashes induced by topical tacrolimus ointment in rats, suggesting that the combination application with olopatadine and tacrolimus ointment is useful for improving medication adherence with tacrolimus ointment treatment in patients with atopic dermatitis. PMID- 26362750 TI - Silibinin alleviates high glucose-suppressed osteogenic differentiation of human bone marrow stromal cells via antioxidant effect and PI3K/Akt signaling. AB - High glucose is one of the possible causes for osteoporosis and fracture in diabetes mellitus. Our previous study showed that silibinin can increase osteogenic effect by stimulating osteogenic genes expression in human bone marrow stem cells (hBMSCs). However, no study has yet investigated the effect of silibinin on osteogenic differentiation of hBMSCs cultured with high glucose. The aim of this study was to evaluate the influence of high glucose on osteogenic differentiation of hBMSCs and to determine if silibinin can alleviate those effects. In this study, the hBMSCs were cultured in an osteogenic medium with physiological (normal glucose, NG, 5.5mM) or diabetic (high glucose, HG, 30mM). The effects of silibinin on HG-induced osteogenic differentiation were evaluated by alkaline phosphatas (ALP) activity assay, Von Kossa staining and real time polymerase chain reaction. HG-induced oxidative damage was also assessed. Western blot were performed to examine the role of PI3K/Akt pathway. We demonstrated that HG suppressed osteogenic differentiation of hBMSCs, manifested by a decrease in expression of osteogenic markers and an increase of oxidative damage markers including reactive oxygen species and lipid peroxide (MDA). Remarkably, all of the observed oxidative damage and osteogenic dysfunction induced by HG were inhibited by silibinin. Furthermore, the PI3K/Akt pathway was activated by silibinin. These results demonstrate that silibinin may attenuate HG-mediated hBMSCs dysfunction through antioxidant effect and modulation of PI3K/Akt pathway, suggesting that silibinin may be a superior drug candidate for the treatment of diabetes related bone diseases. PMID- 26362751 TI - Ethyl rosmarinate relaxes rat aorta by an endothelium-independent pathway. AB - Ethyl rosmarinate is an ester derivative of rosmarinic acid, a major constituent of Hyptis suaveolens. The present study investigated the vasorelaxant mechanism of ethyl rosmarinate in isolated rat aortic rings using an organ bath system. Ethyl rosmarinate (0.1 uM-3mM) produced concentration-dependent relaxation in aortic rings pre-contracted with phenylephrine (10 uM), exhibiting a pD2 value of 4.56 +/- 0.08 and an Emax value of 93.82 +/- 5.00% (in endothelium-intact rings), as well as a pD2 value of 4.42 +/- 0.05 and an Emax value of 92.10 +/- 3.78% (in endothelium-denuded rings). In the endothelium-denuded rings, the vasorelaxant effect of ethyl rosmarinate was reduced by only 4-aminopyridine (1mM); however, this was not the case with tetraethylammonium (5mM), glibenclamide (10 uM), barium chloride (1mM), and 1H-[1,2,4] oxadiazolo [4,3-a]quinoxalin-1-one (ODQ, 1 uM). Ethyl rosmarinate also reduced the contraction induced by phenylephrine (10 uM) and caffeine (20mM) in a Ca(2+)-free solution, and inhibited the contraction induced by increasing extracellular Ca(2+) influx, which was induced by KCl (80 mM). Ethyl rosmarinate (10 uM) inhibits concentration-response curves for phenylephrine, while in the same concentration of ethyl rosmarinate has no effect on contractions induced by increasing concentrations of calcium in the presence of high extracellular potassium. Our results suggests that ethyl rosmarinate induces relaxation in aortic rings via an endothelium-independent pathway, which involves the opening of voltage-gated potassium (Kv) channels and the blockade of both Ca(2+)release from intracellular stores and extracellular Ca(2+) influx. Moreover, ethyl-rosmarinate acts on the extracellular Ca(2+) influx inhibition by interacting with voltage-operated calcium channels (VOCCs) and receptor-operated calcium channels (ROCCs). PMID- 26362752 TI - Chronic fluoxetine treatment increases NO bioavailability and calcium-sensitive potassium channels activation in rat mesenteric resistance arteries. AB - Fluoxetine, a selective serotonin reuptake inhibitor (SSRI), has effects beyond its antidepressant properties, altering, e.g., mechanisms involved in blood pressure and vasomotor tone control. Although many studies have addressed the acute impact of fluoxetine on the cardiovascular system, there is a paucity of information on the chronic vascular effects of this SSRI. We tested the hypothesis that chronic fluoxetine treatment enhances the vascular reactivity to vasodilator stimuli by increasing nitric oxide (NO) signaling and activation of potassium (K+) channels. Wistar rats were divided into two groups: (I) vehicle (water for 21 days) or (II) chronic fluoxetine (10 mg/kg/day in the drinking water for 21 days). Fluoxetine treatment increased endothelium-dependent and independent vasorelaxation (analyzed by mesenteric resistance arteries reactivity) as well as constitutive NO synthase (NOS) activity, phosphorylation of eNOS at Serine1177 and NO production, determined by western blot and fluorescence. On the other hand, fluoxetine treatment did not alter vascular expression of neuronal and inducible NOS or guanylyl cyclase (GC). Arteries from fluoxetine-treated rats exhibited increased relaxation to pinacidil. Increased acetylcholine vasorelaxation was abolished by a calcium-activated K+ channel (KCa) blocker, but not by an inhibitor of KATP channels. On the other hand, vascular responses to Bay 41-2272 and 8-bromo-cGMP were similar between the groups. In conclusion, chronic fluoxetine treatment increases endothelium dependent and independent relaxation of mesenteric resistance arteries by mechanisms that involve increased eNOS activity, NO generation, and KCa channels activation. These effects may contribute to the cardiovascular effects associated with chronic fluoxetine treatment. PMID- 26362753 TI - Diagnostic utility of QuantiFERON-TB Gold In-Tube test in pediatric tuberculosis disease in Taiwanese children. AB - PURPOSE: To compare the performance of a commercial interferon-gamma release assay, QuantiFERON TB Gold-in-Tube (QFG-IT) with the tuberculin skin test (TST) in Taiwanese children for the diagnosis of active tuberculosis (TB). METHODS: A retrospective chart analysis of pediatric patients (<18 years of age) who underwent QFG-IT tests and TST for the confirmation of active TB between January 2008 and June 2014. RESULTS: The sensitivity of QFG-IT was 100% [95% confidence interval (CI): 63.1-100], versus sensitivity of 62.5% for TST (95% CI 24.5-91.5). The positive predictive value of QFG-IT was 100 (95% CI: 89.7-100), while the negative predictive value for TST was 86.9% (95% CI: 67-96.3). Among three patients with Bacillus Calmette-Guerin (BCG) osteitis, two patients with TST were positive, but all tested samples for QFG-IT were negative. CONCLUSION: QFG-IT assay was more sensitive for the diagnosis of TB disease than TST in an intermediate burden population with universal neonatal BCG vaccination. The increased recognition of BCG induced osteitis in recent years has alerted physicians that BCG induced lesions should be suspected when TST is positive but QFG-IT is negative. Despite higher costs for QFG-IT than TST, they have additional value for the diagnosis of active TB and should be performed when a diagnosis of TB remains in doubt. PMID- 26362754 TI - Emergence of Streptococcus suis serotype 9 infection in humans. PMID- 26362756 TI - Occurrence and risk indicators of medication-related osteonecrosis of the jaw after dental extraction: a systematic review and meta-analysis. AB - AIMS: The primary objective was to assess the occurrence rate of Medication Related OsteoNecrosis of the Jaw (MRONJ) after dental extraction in patients treated with Antiresorptive Drugs (ARD) for OsteoPorosis (OP) or for oncological reasons. The secondary objective was to compare the extraction techniques regarding the occurrence of MRONJ. MATERIALS AND METHODS: A systematic search in PubMed/MEDLINE, EMBASE and LILACS databases was performed. Prospective studies considering human patients treated with ARD and providing information regarding the occurrence of MRONJ after dental extraction were selected. Meta-analysis for incidence of MRONJ at the patient level was performed. The effect of administration route and surgical technique on MRONJ was evaluated. RESULTS: The risk of MRONJ after dental extraction was significantly higher in patients treated with ARD for oncological reasons (3.2%) than in those treated with per os ARD for OP (0.15%) (p < 0.0001). Dental extraction performed with adjusted extraction protocols decreased significantly MRONJ development. Potential risk indicators such as concomitant medications and pre-existing osteomyelitis were identified. CONCLUSION: The risk of MRONJ after dental extraction in patients treated with ARD exists, especially in patients treated for oncologic reasons. This risk tends to decrease with adjusted extraction protocols. PMID- 26362755 TI - Therapeutic strategies targeting cancer stem cells. AB - Cancer stem cells (CSCs) are undifferentiated cancer cells with a high tumorigenic activity, the ability to undergo self-renewal, and a multilineage differentiation potential. Cancer stem cells are responsible for the development of tumor cell heterogeneity, a key feature for resistance to anticancer treatments including conventional chemotherapy, radiation therapy, and molecularly targeted therapy. Furthermore, minimal residual disease, the major cause of cancer recurrence and metastasis, is enriched in CSCs. Cancer stem cells also possess the property of "robustness", which encompasses several characteristics including a slow cell cycle, the ability to detoxify or mediate the efflux of cytotoxic agents, resistance to oxidative stress, and a rapid response to DNA damage, all of which contribute to the development of therapeutic resistance. The identification of mechanisms underlying such characteristics and the development of novel approaches to target them will be required for the therapeutic elimination of CSCs and the complete eradication of tumors. In this review, we focus on two prospective therapeutic approaches that target CSCs with the aim of disrupting their quiescence or redox defense capability. PMID- 26362757 TI - A first-level evaluation of a school-based family programme for adolescent social, emotional and behavioural difficulties. AB - This study is a first-level evaluation of an intervention targeted at adolescents with social, emotional and behavioural difficulties in Irish post-primary schools. It is a combined implementation of the Working Things Out adolescent programme and the Parents Plus Adolescent Programme (WTOPPAP). Overall, 47 parents and their children (mean age: 13.81 years) took part in the study. The study used a repeated measures design to assess change at pre- and post intervention and 5-month follow-up using the Strengths and Difficulties Questionnaire, McMaster General Functioning Scale, Goal Attainment (parent- and adolescent-rated), Parent Stress Scale and Kansas Parenting Satisfaction Scale (parent-rated) as assessment measures. This study found that parent-rated child total difficulties and adolescent-rated emotional difficulties significantly improved from pre-test to 5-month follow-up. Parent- and adolescent-rated goals, and parent-rated child conduct difficulties, parental stress and satisfaction with parenting also significantly improved from pre- to post-test. These gains were largely maintained at 5-month follow-up. These findings indicate that the WTOPPAP may be an effective intervention for adolescents with emotional and behavioural difficulties and their parents. It was demonstrated that a manualised family intervention could be effectively rolled out at a number of school locations, with delivery and evaluation being conducted by school staff. Further implications are also discussed. PMID- 26362758 TI - Efficient therapy of ischaemic lesions with VEGF121-fibrin in an animal model of systemic sclerosis. AB - BACKGROUND: In systemic sclerosis (SSc), chronic and uncontrolled overexpression of vascular endothelial growth factor (VEGF) results in chaotic vessels, and intractable fingertip ulcers. Vice versa, VEGF is a potent mediator of angiogenesis if temporally and spatially controlled. We have addressed this therapeutic dilemma in SSc by a novel approach using a VEGF121 variant that covalently binds to fibrin and gets released on demand by cellular enzymatic activity. Using University of California at Davis (UCD)-206 chickens, we tested the hypothesis that cell-demanded release of fibrin-bound VEGF121 leads to the formation of stable blood vessels, and clinical improvement of ischaemic lesions. METHODS: Ninety-one early and late ischaemic comb and neck skin lesions of UCD 206 chickens were treated locally with VEGF121-fibrin, fibrin alone, or left untreated. After 1 week of treatment the clinical outcome was assessed. Angiogenesis was studied by immunofluorescence staining of vascular markers quantitatively analysed using TissueQuest. RESULTS: Overall, 79.3% of the lesions treated with VEGF121-fibrin showed clinical improvement, whereas 71.0% of fibrin treated controls, and 93.1% of untreated lesions deteriorated. This was accompanied by significantly increased growth of stable microvessels, upregulation of the proangiogenic VEGFR-2 and its regulator TAL-1, and increase of endogenous endothelial VEGF expression. CONCLUSIONS: Our findings in the avian model of SSc suggest that cell-demanded release of VEGF121 from fibrin matrix induces controlled angiogenesis by differential regulation of VEGFR-1 and VEGFR-2 expression, shifting the balance towards the proangiogenic VEGFR-2. The study shows the potential of covalently conjugated VEGF-fibrin matrices for the therapy of ischaemic lesions such as fingertip ulcers. PMID- 26362761 TI - Special Issue--Investigating the neurotoxicity of flame retardants: past, present, and future. PMID- 26362760 TI - Utility of component analyses in subjects undergoing sublingual immunotherapy for peanut allergy. AB - BACKGROUND: Sublingual immunotherapy (SLIT) with peanut changes clinical and immune responses in most peanut-allergic individuals, but the response is highly variable. OBJECTIVE: We sought to examine the component-specific effects of peanut SLIT and determine whether peanut component testing could predict the outcome of a double-blind, placebo-controlled food challenge (DBPCFC) after 12 months of peanut SLIT. METHODS: We included 33 subjects who underwent peanut SLIT with a DBPCFC of 2500 mg of peanut protein performed after 12 months of therapy. Plasma samples from baseline and after 12 months of peanut SLIT were assayed using ImmunoCAP for IgE and IgG4 against whole peanut, Ara h 1, Ara h 2, Ara h 3, Ara h 8, and Ara h 9. RESULTS: Following 12 months of SLIT, 10 subjects (30%) passed the DBPCFC without symptoms and were considered desensitized. Subjects that failed the DBPCFC tolerated a median of 460 mg peanut protein (range: 10 1710 mg). The desensitized group had significantly lower baseline levels of IgE against peanut (median 40.8 vs. 231 kUA /L, P = 0.0082), Ara h 2 (median 17 vs. 113 kUA /L, P = 0.0082), and Ara h 3 (median 0.3 vs. 8.5 kUA /L, P = 0.0396). ROC curves indicated that baseline IgE against peanut and Ara h 2 were equally effective at discriminating between the two groups (AUC = 0.7957, P = 0.007752 for both). CONCLUSION AND CLINICAL RELEVANCE: In this cohort of subjects undergoing SLIT for peanut allergy, lower baseline levels of IgE against Ara h 2, Ara h 3, and peanut were associated with successful desensitization. PMID- 26362759 TI - Dense genotyping of immune-related loci in idiopathic inflammatory myopathies confirms HLA alleles as the strongest genetic risk factor and suggests different genetic background for major clinical subgroups. AB - OBJECTIVES: The idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of rare autoimmune diseases characterised by muscle weakness and extramuscular manifestations such as skin rashes and interstitial lung disease. We genotyped 2566 IIM cases of Caucasian descent using the Immunochip; a custom array covering 186 established autoimmune susceptibility loci. The cohort was predominantly comprised of patients with dermatomyositis (DM, n=879), juvenile DM (JDM, n=481), polymyositis (PM, n=931) and inclusion body myositis (n=252) collected from 14 countries through the Myositis Genetics Consortium. RESULTS: The human leucocyte antigen (HLA) and PTPN22 regions reached genome-wide significance (p<5*10(-8)). Nine regions were associated at a significance level of p<2.25*10(-5), including UBE2L3, CD28 and TRAF6, with evidence of independent effects within STAT4. Analysis of clinical subgroups revealed distinct differences between PM, and DM and JDM. PTPN22 was associated at genome-wide significance with PM, but not DM and JDM, suggesting this effect is driven by PM. Additional suggestive associations including IL18R1 and RGS1 in PM and GSDMB in DM were identified. HLA imputation confirmed that alleles HLA-DRB1*03:01 and HLA B*08:01 of the 8.1 ancestral haplotype (8.1AH) are most strongly associated with IIM, and provides evidence that amino acids within the HLA, such as HLA-DQB1 position 57 in DM, may explain part of the risk in this locus. Associations with alleles outside the 8.1AH reveal differences between PM, DM and JDM. CONCLUSIONS: This work represents the largest IIM genetic study to date, reveals new insights into the genetic architecture of these rare diseases and suggests different predominating pathophysiology in different clinical subgroups. PMID- 26362763 TI - Molecular marker development from transcript sequences and germplasm evaluation for cultivated peanut (Arachis hypogaea L.). AB - Molecular markers are important tools for genotyping in genetic studies and molecular breeding. The SSR and SNP are two commonly used marker systems developed from genomic or transcript sequences. The objectives of this study were to: (1) assemble and annotate the publicly available ESTs in Arachis and the in house short reads, (2) develop and validate SSR and SNP markers, and (3) investigate the genetic diversity and population structure of the peanut breeding lines and the U.S. peanut mini core collection using developed SSR markers. An NCBI EST dataset with 252,951 sequences and an in-house 454 RNAseq dataset with 288,701 sequences were assembled separately after trimming. Transcript sequence comparison and phylogenetic analysis suggested that peanut is closer to cowpea and scarlet bean than to soybean, common bean and Medicago. From these two datasets, 6455 novel SSRs and 11,902 SNPs were identified. Of the discovered SSRs, 380 representing various SSR types were selected for PCR validation. The amplification rate was 89.2 %. Twenty-two (6.5 %) SSRs were polymorphic between at least one pair of four genotypes. Sanger sequencing of PCR products targeting 110 SNPs revealed 13 true SNPs between tetraploid genotypes and 193 homoeologous SNPs within genotypes. Eight out of the 22 polymorphic SSR markers were selected to evaluate the genetic diversity of Florida peanut breeding lines and the U.S. peanut mini core collection. This marker set demonstrated high discrimination power by displaying an average polymorphism information content value of 0.783, a combined probability of identity of 10(-11), and a combined power of exclusion of 0.99991. The structure analysis revealed four sub-populations among the peanut accessions and lines evaluated. The results of this study enriched the peanut genomic resources, provided over 6000 novel SSR markers and the credentials for true peanut SNP marker development, and demonstrated the power of newly developed SSR markers in genotyping peanut germplasm and breeding materials. PMID- 26362762 TI - An increased need for dietary cysteine in support of glutathione synthesis may underlie the increased risk for mortality associated with low protein intake in the elderly. AB - Restricted dietary intakes of protein or essential amino acids tend to slow aging and boost lifespan in rodents, presumably because they downregulate IGF I/Akt/mTORC1 signaling that acts as a pacesetter for aging and promotes cancer induction. A recent analysis of the National Health and Nutrition Examination Survey (NHANES) III cohort has revealed that relatively low protein intakes in mid-life (under 10 % of calories) are indeed associated with decreased subsequent risk for mortality. However, in those over 65 at baseline, such low protein intakes were associated with increased risk for mortality. This finding accords well with other epidemiology correlating relatively high protein intakes with lower risk for loss of lean mass and bone density in the elderly. Increased efficiency of protein translation reflecting increased leucine intake and consequent greater mTORC1 activity may play a role in this effect; however, at present there is little solid evidence that leucine supplementation provides important long-term benefits to the elderly. Aside from its potential pro anabolic impact, higher dietary protein intakes may protect the elderly in another way-by providing increased amino acid substrate for synthesis of key protective factors. There is growing evidence, in both rodents and humans, that glutathione synthesis declines with increasing age, likely reflecting diminished function of Nrf2-dependent inductive mechanisms that boost expression of glutamate cysteine ligase (GCL), rate-limiting for glutathione synthesis. Intracellular glutathione blunts the negative impact of reactive oxygen species (ROS) on cell health and functions both by acting as an oxidant scavenger and by opposing the pro-inflammatory influence of hydrogen peroxide on cell signaling. Fortunately, since GCL's K m for cysteine is close to intracellular cysteine levels, increased intakes of cysteine-achieved from whole proteins or via supplementation with N-acetylcysteine (NAC)-can achieve a compensatory increase in glutathione synthesis, such that more youthful tissue levels of this compound can be restored. Supplementation with phase 2 inducers-such as lipoic acid-can likewise increase glutathione levels by promoting increased GCL expression. In aging humans and/or rodents, NAC supplementation has exerted favorable effects on vascular health, muscle strength, bone density, cell-mediated immunity, markers of systemic inflammation, preservation of cognitive function, progression of neurodegeneration, and the clinical course of influenza-effects which could be expected to lessen mortality and stave off frailty. Hence, greater cysteine availability may explain much of the favorable impact of higher protein intakes on mortality and frailty risk in the elderly, and joint supplementation with NAC and lipoic acid could be notably protective in the elderly, particularly in those who follow plant-based diets relatively low in protein. It is less clear whether the lower arginine intake associated with low-protein diets has an adverse impact on vascular health. PMID- 26362764 TI - What Constitutes an "Adequate" Trial in Migraine Prevention? AB - Comprehensively assessing the quality of prior preventive treatment attempts often reveals modifiable variables that may account for treatment failure. Similarly, a comprehensive and systematic approach when planning a preventive medication trial is critical for optimizing the chances of treatment success. In this review, we summarize the key elements to be included when assessing the adequacy of a preventive treatment trial. We have developed and included checklists that can be used by providers to improve their assessments of prior preventive treatment trials and to assist with planning a high-quality treatment trial with a new migraine preventive medication. PMID- 26362765 TI - The Nature, Extent, and Consequences of Genetic Variation in the opa Repeats of Notch in Drosophila. AB - Polyglutamine (pQ) tracts are abundant in proteins co-interacting on DNA. The lengths of these pQ tracts can modulate their interaction strengths. However, pQ tracts >40 residues are pathologically prone to amyloidogenic self-assembly. Here, we assess the extent and consequences of variation in the pQ-encoding opa repeats of Notch in Drosophila melanogaster. We use Sanger sequencing to genotype opa sequences ([Formula: see text]-CAX repeats), which have resisted assembly using short sequence reads. While most sampled lines carry the major allele opa31 encoding Q13HQ17 or the opa32 allele encoding Q13HQ18, many lines carry rare alleles encoding pQ tracts >32 residues: opa33a (Q14HQ18), opa33b (Q15HQ17), opa34 (Q16HQ17), opa35a1/opa35a2 (Q13HQ21), opa36 (Q13HQ22), and opa37 (Q13HQ23). Only one rare allele encodes a tract <31 residues: opa23 (Q13-Q10). This opa23 allele shortens the pQ tract while simultaneously eliminating the interrupting histidine. We introgressed these opa variant alleles into common backgrounds and measured the frequency of Notch-type phenotypes. Homozygotes for the short and long opa alleles have defects in embryonic survival and sensory bristle organ patterning, and sometimes show wing notching. Consistent with functional differences between Notch opa variants, we find that a scute inversion carrying the rare opa33b allele suppresses the bristle patterning defect caused by achaete/scute insufficiency, while an equivalent scute inversion carrying opa31 manifests the patterning defect. Our results demonstrate the existence of potent pQ variants of Notch and the need for long read genotyping of key repeat variables underlying gene regulatory networks. PMID- 26362766 TI - Flux Control in a Defense Pathway in Arabidopsis thaliana Is Robust to Environmental Perturbations and Controls Variation in Adaptive Traits. AB - The connections leading from genotype to fitness are not well understood, yet they are crucial for a diverse set of disciplines. Uncovering the general properties of biochemical pathways that influence ecologically important traits is an effective way to understand these connections. Enzyme flux control (or, control over pathway output) is one such pathway property. The flux-controlling enzyme in the antiherbivory aliphatic glucosinolate pathway of Arabidopsis thaliana has majority flux control under benign greenhouse conditions and has evidence of nonneutral evolution. However, it is unknown how patterns of flux control may change in different environments, or if insect herbivores respond to differences in pathway flux. We test this, first through genetic manipulation of the loci that code for the aliphatic glucosinolate pathway enzymes under a variety of environments (reduced water, reduced soil nutrients, leaf wounding and methyl jasmonate treatments), and find that flux control is consistently in the first enzyme of the pathway. We also find that a generalist herbivore, Trichoplusia ni, modifies its feeding behavior depending on the flux through the glucosinolate pathway. The influence over herbivore behavior combined with the consistency of flux control suggests that genes controlling flux might be repeatedly targeted by natural selection in diverse environments and species. PMID- 26362767 TI - Slit Binding via the Ig1 Domain Is Essential for Midline Repulsion by Drosophila Robo1 but Dispensable for Receptor Expression, Localization, and Regulation in Vivo. AB - The midline repellant ligand Slit and its Roundabout (Robo) family receptors constitute the major midline repulsive pathway in bilaterians. Slit proteins produced at the midline of the central nervous system (CNS) signal through Robo receptors expressed on axons to prevent them from crossing the midline, and thus regulate connectivity between the two sides of the nervous system. Biochemical structure and interaction studies support a model in which Slit binding to the first immunoglobulin-like (Ig1) domain of Robo receptors activates a repulsive signaling pathway in axonal growth cones. Here, we examine the in vivo functional importance of the Ig1 domain of the Drosophila Robo1 receptor, which controls midline crossing of axons in response to Slit during development of the embryonic CNS. We show that deleting Ig1 from Robo1 disrupts Slit binding in cultured Drosophila cells, and that a Robo1 variant lacking Ig1 (Robo1(?Ig1)) is unable to promote ectopic midline repulsion in gain-of-function studies in the Drosophila embryonic CNS. We show that the Ig1 domain is not required for proper expression, axonal localization, or Commissureless (Comm)-dependent regulation of Robo1 in vivo, and we use a genetic rescue assay to show that Robo1(?Ig1) is unable to substitute for full-length Robo1 to properly regulate midline crossing of axons. These results establish a direct link between in vitro biochemical studies of Slit-Robo interactions and in vivo genetic studies of Slit-Robo signaling during midline axon guidance, and distinguish Slit-dependent from Slit-independent aspects of Robo1 expression, regulation, and activity during embryonic development. PMID- 26362768 TI - Synthesis of New Harmine Isoxazoles and Evaluation of their Potential Anti Alzheimer, Anti-inflammatory, and Anticancer Activities. AB - Harmine 1 was extracted from the seeds of Peganum harmala. From this natural molecule, a new series of isoxazole derivatives with complete regiospecificity were prepared using 1,3-dipolar cycloaddition reactions with various arylnitrile oxides. Harmine and its derivatives were characterized by (1)H NMR, (13)C NMR and HRMS. The evaluation of their anti-acetylcholinesterase (AChE), anti-5 lipoxygenase (5-LOX), anti-xanthine oxidase (XOD) and anticancer activities were studied in vitro against AChE, 5-LOX and XOD enzymes, respectively, and in HTC 116, MCF7 and OVCAR-3 cancer cell lines. The prepared derivatives were shown to be inactive against the XOD enzyme (0-38.3 +/- 1.9% at 100 uM). Compound 2 exhibited the best anti-AChE activity (IC50=1.9 +/- 1.5 uM). Derivatives 3a, 3b and 3d had moderate cytotoxic activities (IC50=5.0 +/- 0.3 uM (3a) and IC50=6.3 +/- 0.4 uM (3b) against HCT 116 cells, IC50=5.0 +/- 1.0 uM (3d) against MCF7 cells). PMID- 26362769 TI - Retailer opinions about and compliance with family smoking prevention and tobacco control act point of sale provisions: a survey of tobacco retailers. AB - BACKGROUND: The objectives of this study were to document retailer opinions about tobacco control policy at the point of sale (POS) and link these opinions with store level compliance with sales and marketing provisions of the Tobacco Control Act. METHODS: This study conducted interviews of 252 tobacco retailers in three counties in North Carolina and linked their opinions with in-person observational audit data of their stores' compliance with POS policies. We conducted analyses examining retailer factors associated with noncompliance using Generalized Estimating Equations (GEE) controlling for individual, store, neighborhood, and county factors. RESULTS: Over 90 % of retailers support minors' access provisions and a large minority (over 40 %) support graphic warnings and promotion bans. Low levels of support were found for a potential ban on menthol cigarettes (17 %). Store noncompliance with tobacco control policies was associated with both more reported retailer barriers to compliance and less support for POS policies. Awareness of and source of information about tobacco control regulations were not associated with compliance when accounting for neighborhood and county characteristics. CONCLUSIONS: Retailers expressed some support for a wide range of POS policies. Advocates and government agencies tasked with enforcement can work with retailers as stakeholders to enhance support, mitigate barriers, and promote compliance with tobacco control efforts at the point of sale. PMID- 26362770 TI - Microalbuminuria in non-diabetic patients with unstable angina/non ST-segment elevation myocardial infarction. AB - BACKGROUND: Microalbuminuria (MAU) is defined as an urinary albumin excretion rate between 20-200 mg/l or 30-300 mg/day. It is a surrogate marker for endothelial dysfunction and is independently associated with atherosclerotis in diabetic and in non-diabetic patients. We assessed the prevalence of MAU in non diabetic patients who presented with UA/NSTEMI and the relation of MAU to the severity of coronary artery disease in patients at a cardiac care center in Iraq. METHODS: Seventy non-diabetic patients referred to the Iraqi Center for Heart Disease, Baghdad, between November 1st 2010 and June 1st 2011 with the diagnosis of UA/NSTEMI were included in this study. Physical examination, ECG and echocardiography were performed on all patients. TIMI ("Thrombolysis in Myocardial Infarction") risk score was obtained. Urine samples were collected and sent for quantitative determination of MAU. All patients underwent diagnostic coronary angiography. Data are give as mean (quantitative and percent) +/- SD. RESULTS: Fifty-three men (76%) and 17 (24%) women (mean age 56 +/- 12 years) were investigated. Overall 37 (53%) individuals presented with arterial hypertension and 41 (59%) with a history of smoking. 58 patients (83%) had ischemic ECG changes (defined as ST segment depression more than 1 mm from baseline, and/or T wave inversion), 52 (74%) had echocardiographic findings indicative of ischemia (defined as segmental wall motion abnormalities). Twenty-one (30%) patients tested positive for MAU. There was a significant correlation of echocardiographic signs of ischemia and MAU, (n = 20 (38%), p < 0.01). There was a clear relationship between MAU and TIMI risk score. Additionally, MAU was more common in patients with multivessel coronary artery disease (CAD) (p < 0.001). There was no statistically significant correlation between MAU and mean age, sex, smoking, and blood pressure. CONCLUSION: In this analysis of patients with UA/NSTEMI we found a strong correlation of microalbuminuria with echocardiographic changes and findings in coronary angiography. PMID- 26362771 TI - Giant aneurysm of the left main coronary artery with fistulous communication to the right atrium. AB - The giant coronary artery aneurysm combined with coronary artery fistula is extremely uncommon. In our case, there was a giant aneurysm of the left main coronary artery with fistulous communication to the right atrium, combined with moderate aortic valve regurgitation, which was initially found by transthoracic echocardiogram and subsequently confirmed by the 256-slice multidetector computer tomography (MDCT) coronary angiography. After consultation, the patient received surgical treatment, including the closure of the drainage and origin sites of the aneurysm and the aortic valve replacement. The patient recovered uneventfully. PMID- 26362773 TI - Antinociceptive effect of 1400 W, an inhibitor of inducible nitric oxide synthase, following hind paw incision in rats. AB - Acute tissue damage is accompanied by synthesis of nitric oxide (NO) in the inflamed tissue as well as in the spinal cord. NO release at the spinal level is likely involved in the neuroplastic changes contributing to pain. Also, previous studies indicate that this could be due to the inducible isoform of the nitric oxide synthase (iNOS) enzyme. Though, the role of NO has been investigated in several animal models of nociception, the precise contribution of NO to nociception arising from hind paw incision is unknown, which is a rodent model of postoperative pain. In the present work, we have estimated the formation of NO in Sprague-Dawley rats, both at the site of incision and the corresponding spinal cord levels by Griess assay. Subsequently, naive rats were implanted with chronic indwelling intrathecal (i.t.) catheters. Fixed quantity (30 MUg) of 1400 W, an iNOS inhibitor, was either administered locally into the wound at the time of incision or into the i.t. space, 15 min before hind paw incision. In a different set, i.t. 1400 W was administered, 20 h after incision. Control group received i.t. saline. Nociception was evaluated by guarding score, mechanical allodynia and thermal hyperalgesia. NO level was significantly increased between 4 h - day 1 locally and at 4 h at the spinal level after incision. Local inhibition of iNOS produced transient decrease of guarding (4-12 h) whereas pronounced decrease of guarding and allodynia was evident after spinal inhibition of iNOS. Also, spinal NO level decreased after i.t. drug administration. Post-incision drug treatment resulted in greater antinociceptive effect at day 1 though not on day 2. These results indicate involvement of NO in postincisional nociception in rats. PMID- 26362772 TI - Japanese encephalitis virus replicon-based vaccine expressing enterovirus-71 epitope confers dual protection from lethal challenges. AB - BACKGROUND: To construct safer recombinant flavivirus vaccine, we exploited Japanese encephalitis virus (JEV) replicon-based platform to generate single round infectious particles (SRIPs) that expressed heterologous neutralizing epitope SP70 derived from enterovirus-71 (EV71). Such pseudo-infectious virus particles, named SRIP-SP70, although are not genuine viable viruses, closely mimic live virus infection to elicit immune responses within one round of viral life cycle. RESULTS: We found that, besides gaining of full protection to thwart JEV lethal challenge, female outbred ICR mice, when were immunized with SRIP-SP70 by prime-boost protocol, could not only induce SP70-specific and IgG2a predominant antibodies but also provide their newborns certain degree of protection against EV71 lethal challenge. CONCLUSIONS: Our results therefore exemplify that this vaccination strategy could indeed confer an immunized host a dual protective immunity against subsequent lethal challenge from JEV or EV71. PMID- 26362774 TI - The CB1 Neutral Antagonist Tetrahydrocannabivarin Reduces Default Mode Network and Increases Executive Control Network Resting State Functional Connectivity in Healthy Volunteers. AB - BACKGROUND: The cannabinoid cannabinoid type 1 (CB1) neutral antagonist tetrahydrocannabivarin (THCv) has been suggested as a possible treatment for obesity, but without the depressogenic side-effects of inverse antagonists such as Rimonabant. However, how THCv might affect the resting state functional connectivity of the human brain is as yet unknown. METHOD: We examined the effects of a single 10mg oral dose of THCv and placebo in 20 healthy volunteers in a randomized, within-subject, double-blind design. Using resting state functional magnetic resonance imaging and seed-based connectivity analyses, we selected the amygdala, insula, orbitofrontal cortex, and dorsal medial prefrontal cortex (dmPFC) as regions of interest. Mood and subjective experience were also measured before and after drug administration using self-report scales. RESULTS: Our results revealed, as expected, no significant differences in the subjective experience with a single dose of THCv. However, we found reduced resting state functional connectivity between the amygdala seed region and the default mode network and increased resting state functional connectivity between the amygdala seed region and the dorsal anterior cingulate cortex and between the dmPFC seed region and the inferior frontal gyrus/medial frontal gyrus. We also found a positive correlation under placebo for the amygdala-precuneus connectivity with the body mass index, although this correlation was not apparent under THCv. CONCLUSION: Our findings are the first to show that treatment with the CB1 neutral antagonist THCv decreases resting state functional connectivity in the default mode network and increases connectivity in the cognitive control network and dorsal visual stream network. This effect profile suggests possible therapeutic activity of THCv for obesity, where functional connectivity has been found to be altered in these regions. PMID- 26362776 TI - Dental status of an institutionalized elderly population of 60 years and over in Qingdao, China. AB - OBJECTIVES: The aim of this study was to investigate dental status of institutionalized elders and to relate outcomes with background variables and oral functionality. MATERIALS AND METHODS: Dental status of 512 elders (>=60 years) from eight nursing homes in Qingdao were analyzed in terms of prevalence of decayed (D), missing (M), filled (F), and replaced teeth (R). Multivariate logistic regression was applied to determine relationships with the background variables age, gender, and SES. Prevalence of D, M, and F was analyzed also for separate dental regions. For determining oral functionality, prevalence of dentitions with >=20 teeth without and with tooth replacements was plotted against age. RESULTS: Mean number of D varied from 3.8 at 60 years to 4.6 at 90 years, M from 3.6 at 60 years to 6.7 at 90 years for the lower jaw, and from 3.0 at 60 years to 8.0 at 90 years for the upper. Mean number of F in each jaw was low: 0.2 at 60 years to 0.4 at 90 years. Gender and SES effects were limited. Molars had significantly higher prevalence of D and M than premolar and anterior teeth. Seventy percent of participants of 60 years had >=20 natural teeth and 12 % at 90 years. Including tooth replacements, 96 % at 60 years, and 84 % at 90 years had >=20 teeth. CONCLUSIONS: In this sample of institutionalized elders, dental status of the majority of participants did not represent a functional dentition without tooth replacements. CLINICAL RELEVANCE: Institutionalized Chinese elders showed relatively low numbers of decayed teeth but high numbers of missing teeth. PMID- 26362775 TI - Hippocampal PPARdelta Overexpression or Activation Represses Stress-Induced Depressive Behaviors and Enhances Neurogenesis. AB - BACKGROUND: Emerging data have demonstrated that peroxisome proliferator activated receptor delta (PPARdelta) activation confers a potentially neuroprotective role in some neurodegenerative diseases. However, whether PPARdelta is involved in depression is unknown. METHODS: In this study, PPARdelta was firstly investigated in the chronic mild stress (CMS) and learned helplessness (LH) models of depression. The changes in depressive behaviors and hippocampal neurogenesis were investigated after PPARdelta overexpression by microinfusion of the lentiviral vector, containing the coding sequence of mouse PPARdelta (LV-PPARdelta), into the bilateral dentate gyri of the hippocampus or PPARdelta activation by repeated systemic administration of PPARdelta agonist GW0742 (5 or 10mg/kg.d, i.p., for 21 d). RESULTS: We found that both CMS and LH resulted in a significant decrease in the PPARdelta expression in the hippocampi of mice, and this change was reversed by treatment with the antidepressant fluoxetine. PPARdelta overexpression and PPARdelta activation each suppressed the CMS- and LH-induced depressive-like behavior and produced an antidepressive effect. In vivo or in vitro studies also showed that both overexpression and activation of PPARdelta enhanced proliferation or differentiation of neural stem cells in the hippocampi of mice. CONCLUSIONS: These results suggest that hippocampal PPARdelta upregulation represses stress-induced depressive behaviors, accompanied by enhancement of neurogenesis. PMID- 26362777 TI - Sialoendoscopy as a diagnostic and therapeutic option for obstructive diseases of the large salivary glands-a retrospective analysis. AB - OBJECTIVES: The diagnosis and therapy of obstructive inflammatory disorders of the salivary glands have changed in the past decades following the introduction of sialoendoscopy. The aims of the present study were to analyze the relevance of sialoendoscopy using our own data and to compare the results to those of other studies. PATIENTS AND METHODS: A retrospective analysis of 70 patients was performed, who were treated for obstructive disorders of the parotid and/or submandibular gland in whom sialoendoscopy was indicated. Two categories of interventions were considered: diagnostic interventional sialoendoscopy and endoscope-assisted interventions. Interventional sialoendoscopy procedures requiring extirpation of the gland were included in the analysis, as were abnormal intraductal processes that were detected during endoscopy. RESULTS: Treatment was successful in 58 of 67 (86.6 %) procedures (sialoendoscopy without surgical intervention n = 59; endoscope-assisted surgical intervention n = 8). Based on the underlying disease, the success rate was 88.6 % (n = 39) in patients with obstructive sialadenitis without sialolithiasis and 86.6 % (n = 19) in patients with sialolithiasis. It was not possible to draw definitive conclusions on the underlying disease from the observed pathological intraductal changes. CONCLUSIONS: Sialoendoscopy is an effective and safe diagnostic and therapeutic option with low complication rate. However, limiting factors such as the size or the position of potentially removable obstacles must be taken into consideration. CLINICAL RELEVANCE: The rate of gland extirpations can be reduced using sialoendoscopy. PMID- 26362778 TI - Clinical evaluation comparing the fit of all-ceramic crowns obtained from silicone and digital intraoral impressions. AB - OBJECTIVES: The aim of this study is to compare the fit of all-ceramic crowns fabricated from conventional silicone impressions with the fit of all-ceramic crowns fabricated from intraoral digital impressions. METHODS: Twenty patients with 26 posterior teeth with a prosthetic demand were selected for the study. Two crowns (Straumann-Zerion) were made for each preparation. One crown was fabricated from an intraoral digital impression system (IDI group; Cadent-iTero), and the other crown was fabricated from a conventional one-step silicone impression (CI group; Express Penta Putty and Body Light). To replicate the interface between the crown and the preparation, each crown was cemented on its corresponding clinical preparation with ultra-flow silicone (Express Ultra Light Body). Each crown was embedded in resin to stabilize the registered interface, cut in 2-mm-thick slices in a buco-lingual orientation. Internal misfit was measured in microns using stereomicroscopy with a magnification of *40. Measurements were taken at different landmarks: margin, chamfer angle, axial, crest, and occlusal fosse. After checking for normality, data was analyzed using paired Student's t test (alpha = 0.05). RESULTS: Fit values were significantly affected by the impression technique (p = 0.000). Mean internal misfit and mean marginal misfit were 111.40 MUm (SD = 54.04)/80.29 MUm (SD = 26.24) for the crowns of the IDI group and 173.00 MUm (SD = 92.65)/133.51 MUm (SD = 48.78) for the CI group. CONCLUSION: All-ceramic crowns fabricated from intraoral digital impressions with parallel confocal technology demonstrated a clinically acceptable internal and marginal fit as conventional impression. CLINICAL SIGNIFICANCE: Intraoral digital impressions as initial step to the digital workflow could further improve the marginal adaptation of all ceramic single crowns. TRIAL REGISTRATION: http://www.isrctn.com/ISRCTN16111844. PMID- 26362779 TI - Classification and ordination of main plant communities along an altitudinal gradient in the arid and temperate climates of northeastern Mexico. AB - Quantitative data on the ecology of the main plant communities along an altitudinal gradient in northeastern Mexico were obtained with the aim of identifying the most important environmental variables that affect plant distribution and composition. The main threats to these communities were also investigated. Importance value index (IVi) of the 39 most important species and 16 environmental variables were recorded at 35 altitudinal gradients each spaced at intervals of at least 100-m altitude. Classification and ordination of vegetation showed six well-differentiated but overlapping plant communities: alpine meadow, cold conifer forest, mesic mixed forest, xeric scrub, Tamaulipan piedmont scrub, and halophytic grassland. Altitude, minimum and average temperatures, and organic matter content are the main variables affecting the plant distribution in northeastern Mexico. Urban growth, mechanized agriculture, and changes in land use are the main threats in the short and medium term to plant communities in this area. Climate change also seems to be having an impact at present or in the near future as shown by the presence of exotic shrubs from warmer areas in mesic and temperate areas inhabited by oak and oak-pine forest. PMID- 26362780 TI - Mildly elevated serum total bilirubin levels are negatively associated with carotid atherosclerosis among elderly persons with type 2 diabetes. AB - Diabetes is strongly associated with several mechanisms of tissue damage such as oxidative stress. Serum bilirubin may have a beneficial role in preventing oxidative changes in cardiovascular disease (CVD). Limited information is available on whether serum bilirubin is an independent confounding factor for carotid atherosclerosis among elderly persons with type 2 diabetes. The study subjects were 169 men aged 79 +/- 8 (mean +/- SD) years and 205 women aged 81 +/- 8 years that were enrolled consecutively from patients in the medical department. Carotid intima-media thickness (IMT) and plaque were derived via B-mode ultrasonography. Multiple linear regression analysis showed that serum total bilirubin (beta = -0.160) was significantly associated with carotid IMT. Compared to subjects with a serum total bilirubin of tertile-1 (0.13-0.58 mg/dL), the multivariate-adjusted odds ratio (95% confidence interval) of carotid IMT >=1.0 mm including plaque and carotid plaque was 0.46 (0.23-0.93) and 0.32 (0.17-0.60) in the Tertile-3 group (0.87-1.93 mg/dL), respectively. Next, data were further stratified by gender, age, smoking status, medication and prevalence of CVD. There were no significant differences in serum total bilirubin levels between selected subgroups. Our data demonstrated a negative association between serum total bilirubin and carotid atherosclerosis among elderly persons with type 2 diabetes. PMID- 26362781 TI - Bradyrhizobium viridifuturi sp. nov., encompassing nitrogen-fixing symbionts of legumes used for green manure and environmental services. AB - Symbiotic nitrogen-fixing bacteria, commonly called rhizobia, are agronomically important because they can provide significant amounts of nitrogen to plants and help in recovery of impoverished soils and improvement of degraded environments. In recent years, with advances in molecular techniques, several studies have shown that these bacteria have high levels of genetic diversity, resulting in taxonomic reclassifications and descriptions of new species. However, despite the advances achieved, highly conserved 16S ribosomal genes (16S rRNA) do not elucidate differences between species of several genera, including the genus Bradyrhizobium. Other methodologies, such as multilocus sequence analysis (MLSA), have been used in such cases, with good results. In this study, three strains (SEMIAs 690T, 6387 and 6428) of the genus Bradyrhizobium, isolated from nitrogen fixing nodules of Centrosema and Acacia species, without clear taxonomic positions, were studied. These strains differed from genetically closely related species according to the results of MLSA of four housekeeping genes (dnaK, glnII, gyrB and recA) and nucleotide identities of the concatenated genes with those of related species ranged from 87.8 % to 95.7 %, being highest with Bradyrhizobium elkanii. DNA-DNA hybridization (less than 32 % DNA relatedness) and average nucleotide identity values of the whole genomes (less than 90.5 %) indicated that these strains represented a novel species, and phenotypic traits were determined. Our data supported the description of the SEMIA strains as Bradyrhizobium viridifuturi sp. nov., and SEMIA 690T ( = CNPSo 991T = C 100aT = BR 1804T = LMG 28866T), isolated from Centrosema pubescens, was chosen as type strain. PMID- 26362782 TI - Deep peroneal nerve palsy with isolated lateral compartment syndrome secondary to peroneus longus tear: a report of two cases and a review of the literature. AB - Drop foot is typically caused by neurologic disease such as lumbar disc herniation, but we report two rare cases of deep peroneal nerve palsy with isolated lateral compartment syndrome secondary to peroneus longus tears. Both patients developed mild pain in the lower legs while playing sport, and were aware of drop foot. As compartment pressures were elevated, fasciotomy was performed immediately, and the tendon of the peroneus longus was completely detached from its proximal origin. The patients were able to return their original sports after 3 months, and clinical examination revealed no hypesthesia or muscle weakness in the deep peroneal nerve area at the time of last follow-up. The common peroneal nerve pierced the deep fascia and lay over the fibular neck, which formed the floor of a short tunnel (the so-called fibular tunnel), then passed the lateral compartment just behind the peroneus longus. The characteristic anatomical situation between the fibular tunnel and peroneus longus might have caused deep peroneal nerve palsy in these two cases after hematoma adjacent to the fibular tunnel increased lateral compartment pressure. PMID- 26362784 TI - Patient Reported Kneeling Ability in Fixed and Mobile Bearing Knee Arthroplasty. AB - Kneeling is an important function of the knee joint required for many daily activities. Bearing type is thought to influence functional outcome following UKA and TKA. Self-reported kneeling ability was recorded in 471 UKA and 206 TKA patients with fixed or mobile bearing implants. Kneeling ability was recorded from the Oxford Knee Score question 7. The self-reported ability to kneel was similar in patients with fixed and mobile bearing UKA implants following surgery. In TKA, greater proportions of patients were able to kneel in the fixed compared to the mobile bearing groups up to two years after surgery indicating that self reported kneeling ability is enhanced in fixed compared to mobile bearing TKA. PMID- 26362783 TI - Platelet-rich plasma versus autologous blood versus steroid injection in lateral epicondylitis: systematic review and network meta-analysis. AB - BACKGROUND: Clinical outcomes between the use of platelet-rich plasma (PRP), autologous blood (AB) and corticosteroid (CS) injection in lateral epicondylitis are still controversial. MATERIALS AND METHODS: A systematic review and network meta-analysis of randomized controlled trials was conducted with the aim of comparing relevant clinical outcomes between the use of PRP, AB and CS injection. Medline and Scopus databases were searched from inception to January 2015. A network meta-analysis was performed by applying weight regression for continuous outcomes and a mixed-effect Poisson regression for dichotomous outcomes. RESULTS: Ten of 374 identified studies were eligible. When compared to CS, AB injection showed significantly improved effects with unstandardized mean differences (UMD) in pain visual analog scale (VAS), Disabilities of Arm Shoulder and Hand (DASH), Patient-Related Tennis Elbow Evaluation (PRTEE) score and pressure pain threshold (PPT) of -2.5 (95 % confidence interval, -3.5, -1.5), -25.5 (-33.8, -17.2), -5.3 (-9.1, -1.6) and 9.9 (5.6, 14.2), respectively. PRP injections also showed significantly improved VAS and DASH scores when compared with CS. PRP showed significantly better VAS with UMD when compared to AB injection. AB injection has a higher risk of adverse effects, with a relative risk of 1.78 (1.00, 3.17), when compared to CS. The network meta-analysis suggested no statistically significant difference in multiple active treatment comparisons of VAS, DASH and PRTEE when comparing PRP and AB injections. However, AB injection had improved DASH score and PPT when compared with PRP injection. In terms of adverse effects, AB injection had a higher risk than PRP injection. CONCLUSIONS: This network meta analysis provided additional information that PRP injection can improve pain and lower the risk of complications, whereas AB injection can improve pain, disabilities scores and pressure pain threshold but has a higher risk of complications. LEVEL OF EVIDENCE: Level I evidence. PMID- 26362785 TI - Preoperative Staphylococcus aureus Screening/Decolonization Protocol Before Total Joint Arthroplasty-Results of a Small Prospective Randomized Trial. AB - To study the prevalence of Staphylococcus aureus carriage and the impact of preoperatively treating carriers in prosthetic joint infection (PJI), a prospective randomized trial was organized. From January 2010 to December 2012, 1028 of 1305 total joint arthroplasties performed were screened, and selected carriers underwent preoperative decolonization. We observed a 22.2% (228/1028) S aureus colonization rate and only 0.8% methicillin-resistant S aureus. Prosthetic joint infection rate was higher, albeit not significantly, in S aureus carriers than among noncarriers-3.9% (9/228) vs 2.0% (16/800). Treated and untreated carriers showed no significant differences-3.4% (3/89) vs 4.3% (6/139). Most of the 14 S aureus PJI occurred in noncarriers suggesting a lack of causal relation between nasal and PJI S aureus. No clear benefit in screening/decolonizing carriers before total joint arthroplasty could be demonstrated. PMID- 26362786 TI - Correction for Tymula et al., Like cognitive function, decision making across the life span shows profound age-related changes. PMID- 26362787 TI - Gradual regime shifts in fairy circles. AB - Large responses of ecosystems to small changes in the conditions--regime shifts- are of great interest and importance. In spatially extended ecosystems, these shifts may be local or global. Using empirical data and mathematical modeling, we investigated the dynamics of the Namibian fairy circle ecosystem as a case study of regime shifts in a pattern-forming ecosystem. Our results provide new support, based on the dynamics of the ecosystem, for the view of fairy circles as a self organization phenomenon driven by water-vegetation interactions. The study further suggests that fairy circle birth and death processes correspond to spatially confined transitions between alternative stable states. Cascades of such transitions, possible in various pattern-forming systems, result in gradual rather than abrupt regime shifts. PMID- 26362789 TI - Correction for Futrell et al., Large-scale evidence of dependency length minimization in 37 languages. PMID- 26362788 TI - Proteomic mapping in live Drosophila tissues using an engineered ascorbate peroxidase. AB - Characterization of the proteome of organelles and subcellular domains is essential for understanding cellular organization and identifying protein complexes as well as networks of protein interactions. We established a proteomic mapping platform in live Drosophila tissues using an engineered ascorbate peroxidase (APEX). Upon activation, the APEX enzyme catalyzes the biotinylation of neighboring endogenous proteins that can then be isolated and identified by mass spectrometry. We demonstrate that APEX labeling functions effectively in multiple fly tissues for different subcellular compartments and maps the mitochondrial matrix proteome of Drosophila muscle to demonstrate the power of APEX for characterizing subcellular proteomes in live cells. Further, we generate "MitoMax," a database that provides an inventory of Drosophila mitochondrial proteins with subcompartmental annotation. Altogether, APEX labeling in live Drosophila tissues provides an opportunity to characterize the organelle proteome of specific cell types in different physiological conditions. PMID- 26362790 TI - [Spinal osteochondroma: diagnostic imaging and treatment. Case reports]. AB - BACKGROUND: Osteochondromas are benign bony tumours, with only 1 to 4% being located in the spine. It occurs more frequently in the cervical spine, with C2 being the vertebra most affected. The neurological presentation is slow due to the growth characteristics of the tumour. Computed axial tomography is the reference method for diagnosis. Surgical management is indicated for patients with neurological impairment or pain. CLINICAL CASE: The first case presents a 21 year-old male with osteochondroma located in the spinous processes of L2, L3 and L4. The second case is a 20-year-old female with multiple osteochondromatosis with tumours at the right lateral mass of C1, with extension to C2 and tumours on the spinous processes of C5 and C7. Both patients presented with painful symptoms, which were resolved after surgical resection of the tumours. CONCLUSIONS: The rarity of these conditions, relevance of a clinical-radiographic diagnosis, and considerations required for surgical treatment are discussed here. PMID- 26362791 TI - Acupuncture in pregnancy. PMID- 26362792 TI - The safety of obstetric acupuncture: forbidden points revisited. AB - BACKGROUND/AIM: Although the safety of acupuncture per se in pregnancy is reasonably well accepted, there remains debate regarding needling at points historically considered to be 'forbidden' during pregnancy. This article reviews the scientific literature on this topic. MAIN FINDINGS: There is no objective evidence of harm following needling at forbidden points, summarised by the following four lines of evidence. (1) In 15 clinical trials (n=823 women receiving n=4549-7234 acupuncture treatments at one or more forbidden points) rates of preterm birth (PTB) and stillbirth following are equivalent to those in untreated control groups and consistent with background rates of these complications in the general population. (2) Observational studies, including a large cohort of 5885 pregnant women needled at forbidden points at all stage of pregnancy, demonstrate that rates of miscarriage, PTB, preterm prelabour rupture of membranes (PPROM), and preterm contractions (preterm labour (PTL) or threatened PTL) are comparable with untreated controls and/or consistent with their anticipated incidence. (3) There is no reliable evidence that acupuncture/electroacupuncture (EA) can induce miscarriage/labour, even under otherwise favourable circumstances such as post-dates pregnancy or intrauterine fetal death. (4) Laboratory experiments using pregnant rats have demonstrated that repeated EA at forbidden points throughout gestation does not influence rates of post-implantation embryonic demise or cause miscarriage, fetal loss or resorption. CONCLUSIONS: These findings are reassuring and will help individualised risk:benefit assessment before treating pregnant women. Given the numerous evidence-based indications for obstetric acupuncture and lack of evidence of harm, risk:benefit assessments will often fall in favour of treatment. PMID- 26362793 TI - A pilot study on the use of acupuncture or pelvic floor muscle training for mixed urinary incontinence. AB - OBJECTIVES: To determine the feasibility and acceptability of traditional Chinese medicine (TCM) acupuncture and pelvic floor muscle training (PFMT) in reducing symptoms and bothersomeness in women with mixed urinary incontinence (MUI); and to estimate the sample size for a full scale trial. METHODS: Thirty-four women with MUI were randomly assigned to either 12 sessions of TCM acupuncture, 12 sessions of PFMT, or to a waiting list control group. Outcome measures included an assessment of interest to participate in the trial, identification of successful recruitment strategies, the appropriateness of eligibility criteria, and compliance with treatment. Clinical outcomes were assessed at baseline and 12 weeks, and included the International Consultation on Incontinence Questionnaire Urinary Incontinence-Short Form (ICIQ-UI SF), expectations of treatment effect, and adverse events. RESULTS: Recruitment was feasible and randomisation worked adequately by means of SurveyMonkey. SurveyMonkey does not permit stratification by ICIQ-UI SF baseline score. Fourteen of 22 women found the treatment options acceptable. The dropout rate was high, especially in the control group (6/12). Outcome forms were completed by 20 of 34 women. The median (IQR) changes of the ICIQ-UI SF scores in the acupuncture, physiotherapy, and waiting list group were 5.5 (2.3 to 6.8), 1.0 (-3.0 to 4.5), and 1.5 (-1.5 to 3.0), respectively, suggesting the need for a full scale trial. CONCLUSIONS: Women with MUI were willing to participate in this study. There is a need for adjusting eligibility criteria. A sample size of 129 women, 43 in three arms, is required. No major adverse events occurred. PMID- 26362794 TI - Withdrawal of ventilation at the patient's request in MND: a retrospective exploration of the ethical and legal issues that have arisen for doctors in the UK. AB - BACKGROUND: Ventilatory support has benefits including prolonging survival for respiratory failure in motor neurone disease (MND). At some point some patients may wish to stop the intervention. The National Institute of Health and Care Excellence (NICE) guidance recommends research is needed on ventilation withdrawal. There is little literature focusing on the issues doctors encounter when withdrawing ventilation at the request of a patient. AIM: To identify and explore with doctors the ethical and legal issues that they had encountered in the withdrawal of ventilation at the request of a patient with MND. METHOD: A retrospective thematic analysis of interviews of 24 doctors (including palliative care, respiratory, neurology and general practice) regarding their experiences with withdrawal of ventilation support from patients with MND. RESULTS: Respondents found withdrawal of ventilation at the request of patients with MND to pose legal, ethical and moral challenges in five themes: ethical and legal rights to withdrawal from treatment; discussions with family; discussions with colleagues; experiences of legal advice; issues contributing to ethical complexity. Though clear about the legality of withdrawal of treatment in theory, the practice led to ethical and moral uncertainty and mixed feelings. Many respondents had experienced negative reactions from other healthcare professionals when these colleagues were unclear of the distinction between palliation of symptoms, withdrawal of treatment and assisted death. CONCLUSIONS: Legal, ethical and practical guidance is needed for professionals who support a patient with MND who wishes to withdraw from ventilation. Open discussion of the ethical challenges is needed as well as education and support for professionals. PMID- 26362797 TI - Abstracts 2015. PMID- 26362795 TI - Effects of acotiamide on esophageal motor function and gastroesophageal reflux in healthy volunteers. AB - BACKGROUND: The prevalence of gastroesophageal reflux disease (GERD) has been increasing worldwide, with proton pump inhibitor (PPI) administration the current mainstay therapy for affected individuals. However, PPI efficacy is insufficient especially for non-erosive reflux disease. Although it has been reported that prokinetic drugs improve GERD, their effects on esophageal function remain to be clearly investigated. In the present study, we evaluated the direct effects of acotiamide, a novel prokinetic agent for the treatment of functional dyspepsia, on esophageal motor function and gastroesophageal reflux. METHODS: Ten adult healthy volunteers (average age 24 years, range 20-36 years; 7 males, 3 females) were enrolled. Esophageal body peristaltic contractions and lower esophageal sphincter (LES) pressure with and without acotiamide administration were recorded using high resolution manometry using a cross-over protocol. Total and acidic reflux levels for 24 h and during the postprandial period were also recorded using a multichannel intraluminal impedance and pH monitoring system. Data were analyzed blind by one observer. RESULTS: Acotiamide at a standard dose of 300 mg/day did not significantly stimulate esophageal motor function. Although the frequency of swallows with weak contraction tended to decrease with acotiamide administration, the difference as compared to no administration was not statistically significant. In addition, the drug neither decreased total or postprandial gastroesophageal acid/non-acid reflux events nor accelerated esophageal clearance time. CONCLUSIONS: Acotiamide, a novel gastrointestinal motility modulator, at a standard dose did not significantly affect esophageal motor functions or gastroesophageal reflux in healthy adults. Additional investigations with GERD patients are necessary to elucidate its clinical significance. TRIAL REGISTRATION: This study was registered on 1st August 2013 with the University Hospital Medical Information Network (UMIN) clinical trials registry, as number: UMIN000011260. PMID- 26362796 TI - Hormone signaling requirements for the conversion of non-mammary mouse cells to mammary cell fate(s) in vivo. AB - Mammotropic hormones and growth factors play a very important role in mammary growth and differentiation. Here, hormones including Estrogen, Progesterone, Prolactin, their cognate receptors, and the growth factor Amphiregulin, are tested with respect to their roles in signaling non-mammary cells from the mouse to redirect to mammary epithelial cell fate(s). This was done in the context of glandular regeneration in pubertal athymic female mice. Our previous studies demonstrated that mammary stem cell niches are recapitulated during gland regeneration in vivo. During this process, cells of exogenous origin cooperate with mammary epithelial cells to form mammary stem cell niches and thus respond to normal developmental signals. In all cases tested with the possible exception of estrogen receptor alpha (ER-alpha), hormone signaling is dispensable for non mammary cells to undertake mammary epithelial cell fate(s), proliferate, and contribute progeny to chimeric mammary outgrowths. Importantly, redirected non mammary cell progeny, regardless of their source, have the ability to self-renew and contribute offspring to secondary mammary outgrowths derived from transplanted chimeric mammary fragments; thus suggesting that some of these cells are capable of mammary stem cell/progenitor functions. PMID- 26362798 TI - A closed-circuit anesthesia ventilator facilitates significant reduction in sevoflurane consumption in clinical practice. PMID- 26362799 TI - The impact of changes in drug availability for hemodynamic management in pheochromocytoma: pret-a-porter or tailor-made? PMID- 26362800 TI - Failure of metyrosine therapy for preoperative management of pheochromocytoma: a case report. AB - PURPOSE: Pheochromocytomas (PHEOS) are rare catecholamine-secreting adrenal tumours requiring surgical resection. Preoperative alpha-adrenergic receptor blockade to prevent intraoperative hypertension has traditionally been achieved with phenoxybenzamine. Due to changes in the availability of phenoxybenzamine in Canada, alternate therapies are needed for patients. We report our first experience using metyrosine, a tyrosine hydroxylase inhibitor, for preoperative management in a symptomatic patient with a unilateral PHEO. CLINICAL FEATURES: A 50-yr-old male was referred to our centre with a history of symptoms suggestive of a catecholamine-secreting PHEO, including tachycardia, diaphoresis, nervousness, and tremor. Computerized tomography revealed a right adrenal mass, and additional positive imaging and elevated urine epinephrine levels supported a diagnosis of PHEO. The patient was admitted to hospital five days prior to surgery, and metyrosine therapy was initiated and titrated to 4 g daily over four days. Despite adequate blood pressure (BP) control leading up to the resection, the initial BP reading in the operating room was 191/106 mmHg, but it subsequently declined and was well controlled during induction (100-110 mmHg systolic BP). Significant hypertension (up to 201/110 mmHg) developed upon tumour manipulation and resolved with phentolamine administration and surgical isolation of the tumour. The patient's BP remained stable throughout the residual part of the procedure and in the recovery room and step-down unit. CONCLUSION: In the case of this patient's PHEO, the use of metyrosine was unsatisfactory in achieving sufficient inhibition of catecholamine synthesis as evidenced by significant intraoperative hypertension. Metyrosine could have a role in preoperative management of these patients, but it may not be optimal as monotherapy for some patients with actively secreting tumours. PMID- 26362801 TI - Type I, II, and III Interferons: Regulating Immunity to Mycobacterium tuberculosis Infection. AB - Interferons (IFNs) are cytokines released by host cells in response to the presence of pathogens or tumor cells. The aim of this review was to present the previously known and new findings about the role of interferons type I and II, and recently discovered type III in Mycobacterium tuberculosis (M. tuberculosis) infection control. Infection of various cell types with M. tuberculosis induce both IFN-alpha and IFN-beta synthesis. The majority of the studies support the findings that IFN type I actually promotes infection with M. tuberculosis. It has been well establish that IFN-gamma has protective function against M. tuberculosis and the other mycobacteria and that the primary source of this cytokine are CD4(+) and CD8(+) T cells. Recently, it has been shown that also the innate lymphocytes, gammadelta T cells, natural killer (NK) T cells, and NK cells can also be the source of IFN-gamma in response to mycobacterial infection. Several studies have shown that CD4(+) T cells protect mice against M. tuberculosis independently of IFN-gamma. The balance between IFN-gamma and different cytokines such as IL-10 and other Th2 cell cytokines is likely to influence disease outcome. Type I IFN appears to be detrimental through at least three separate, but overlapping, type I IFN-mediated mechanisms: induction of excessive apoptosis, specific suppression of Th1 and IFN-gamma responses, and dampening of the immune response by strong IL-10 induction. Recently it has been found that M. tuberculosis infection in A549 lung epithelial cells stimulate up regulation of IFN-lambda genes in vitro. IFN-lambdas also have a role in modulation of Th1/Th2 response. IFN-lambdas are not essential for M. tuberculosis infection control, but can give some contribution in immune response to this pathogen. PMID- 26362802 TI - Factors associated with receiving Pap tests among married immigrant women of Vietnamese origin in southern Taiwan. AB - The purpose of this study was to explore the factors associated with Pap testing among married immigrant women of Vietnamese origin residing in Taiwan, including demographics, knowledge of cervical cancer, knowledge of Pap tests, fatalism, attitudes toward cervical cancer, and barriers to receiving Pap tests. A cross sectional correlational design was used. Data were collected from July 2012 to January 2013. Participants were recruited through snowball sampling in two communities in Southern Taiwan. A total of 451 married immigrant women of Vietnamese origin aged 30 years and over were invited to participate in the study and 427 participated. Data analysis included descriptive statistics and multivariate logistic regression. Participants with no children were significantly less likely to have received a Pap test (odds ratio = 0.278, 95% confidence interval [CI] = 0.135-0.569); each additional point of knowledge about Pap tests increased the likelihood of having a Pap test by 19% (odds ratio = 1.190, 95% CI = 1.093-1.297), and each additional point in barriers to receiving Pap tests decreased the chances of having received a Pap test (odds ratio = 0.714, 95% CI = 0.637-0.800). The results can provide governments with a reference for developing policies for cervical cancer prevention among married immigrant Vietnamese women. PMID- 26362803 TI - Phenotype-associated inbreeding biases estimates of inbreeding depression in a wild bird population. AB - Inbreeding depression is usually quantified by regressing individual phenotypic values on inbreeding coefficients, implicitly assuming there is no correlation between an individual's phenotype and the kinship coefficient to its mate. If such an association between parental phenotype and parental kinship exists, and if the trait of interest is heritable, estimates of inbreeding depression can be biased. Here we first derive the expected bias as a function of the covariance between mean parental breeding value and parental kinship. Subsequently, we use simulated data to confirm the existence of this bias, and show that it can be accounted for in a quantitative genetic animal model. Finally, we use long-term individual-based data for white-throated dippers (Cinclus cinclus), a bird species in which inbreeding is relatively common, to obtain an empirical estimate of this bias. We show that during part of the study period, parents of inbred birds had shorter wings than those of outbred birds, and as wing length is heritable, inbred individuals were smaller, independent of any inbreeding effects. This resulted in the overestimation of inbreeding effects. Similarly, during a period when parents of inbred birds had longer wings, we found that inbreeding effects were underestimated. We discuss how such associations may have arisen in this system, and why they are likely to occur in others, too. Overall, we demonstrate how less biased estimates of inbreeding depression can be obtained within a quantitative genetic framework, and suggest that inbreeding and additive genetic effects should be accounted for simultaneously whenever possible. PMID- 26362804 TI - The reciprocal association between mammographic breast density, hyaluronan synthesis and patient outcome. AB - Low mammographic breast density (MBD) and increased hyaluronan (HA) synthesis have been shown to have adverse effects on breast cancer prognosis. We aimed at elucidating the background of risk associated with mammographic characteristics, MBD and HA and its synthesizing isoforms in an attempt to uncover potential underlying biological mechanisms. MBD and mammographic characteristics of 270 patients were classified according to percentile density (very low density VLD, <=25 %; mixed density MID, >25 %) and the BI-RADS 5th edition lexicon. Breast density and mammographic features were correlated with the localization and expression of HA, CD44, and HAS1-3 isoforms, and their combined effect on patients' survivals was explored. VLD showed an increased level of HA-positive carcinoma cells and stromal HA, HAS2, and HAS3. Tumors presenting as masses had more HA-positive carcinoma cells and more stromal HAS2 and HAS3. Indistinct margin tumors showed more stromal HA and HAS3. Patients who combined both VLD breasts with either high HA in carcinoma cells or stroma showed a worse prognosis compared to low levels (carcinoma cells 58.0 vs. 80.5 %, p = 0.001; stroma 64.2 vs. 79.6 %, p = 0.017), while no similar HA-related effect was observed in MID breasts. Our findings suggest a strong reciprocal relationship between low MBD and HA expression and synthesis. The expression of both factors simultaneously leads to an especially adverse prognostic effect which might have an impact on treatment decision in the future. Moreover, HA around cancer cells may inhibit chemotherapy agents and antibody treatments from reaching cancer cells. PMID- 26362805 TI - Describing sorption of pharmaceuticals to lake and river sediments, and sewage sludge from UNESCO Biosphere Reserve Kristianstads Vattenrike by chromatographic asymmetry factors and recovery measurements. AB - Over the past 30 years a vast number of studies have demonstrated the presence of pharmaceutical residues in the environment. But still knowledge is scarce regarding the interaction of these emerging pollutants with various matrices in nature. A chromatographic system with on-line detection was developed to perform a sorption study of six selected pharmaceuticals to four natural sediments and dewatered digested sewage treatment plant sludge with differing physicochemical characteristics. Sorption effects, measured as asymmetry factors and recoveries, differed pronouncedly among the pharmaceuticals and between the matrices, which could be explained by basic physicochemical properties of the investigated compounds in relation to matrix characteristics. Protonated and deprotonated molecular properties had the greatest importance for sorbate-sorbent interactions. Atenolol, with cationic properties, showed the highest degree of sorption regardless of the matrix studied. Diclofenac and furosemide, both acids, showed the least tendency towards interactions to natural matrices. Among the neutral compounds bendroflumethiazide, carbamazepine and oxazepam, weaker forces, such as van der Waals, aromatic electron donor-acceptor interactions, and hydrogen forces, seemed more important to determine sorption differences. Results revealed that sorption of pharmaceuticals on natural sediments decreased in the order: atenolol (+)>bendroflumethiazide>oxazepam>carbamazepine>diclofenac ( )>furosemide (-). The matrix content of organic matter measured as total organic carbon (TOC) clearly dictated drug sorption. Beside from studying matrix interaction, these results and the developed technique and methodology might find use in the development of new removal processes of pharmaceuticals from wastewater based on improved knowledge concerning chemical interactions to filter materials. PMID- 26362806 TI - Thin layer chromatography coupled with electrospray ionization mass spectrometry for direct analysis of raw samples. AB - Conventional mass spectrometric analysis of raw samples commonly requires sample pretreatment and chromatographic separation using high performance liquid chromatography or gas chromatography, which could be time-consuming and laborious. In this study, thin layer chromatography (TLC) coupled with electrospray ionization mass spectrometry (ESI-MS) was developed for direct analysis of raw samples. The sorbent material of the TLC plate was found to be able to retain the interfering compounds and allow interested analytes to be extracted, ionized and detected by ESI-MS with much reduced matrix interference. Our results showed that this method could be effectively applied in direct analysis of samples containing common interfering compounds, e.g., salts and detergents, and rapid detection and quantitation of target analytes in raw samples. Offline and online separation and detection of different components in mixture samples, e.g., plant extracts, using TLC-ESI-MS were also demonstrated. Overall, this study revealed that TLC-ESI-MS could be a simple, rapid and efficient method for analysis of raw samples. PMID- 26362807 TI - Determination of biogenic amines in beer and wine by capillary electrophoresis tandem mass spectrometry. AB - A capillary electrophoresis-tandem mass spectrometry (CE-MS/MS) method for the simultaneous assessment of nine biogenic amines (spermine, spermidine, putrescine, cadaverine, histamine, phenylethylamine, tryptamine, tyramine, and urocanic acid) in commercial samples of beer and wine is introduced. The samples were submitted to a simple clean-up step with poly(vinylpolypyrrolidone) followed by filtration. Electrophoretic separation in a polyvinyl alcohol (PVA)-coated capillary using 0.5 mol L(-1) acetic acid (pH 2.5) as background electrolyte and detection by electrospray-tandem mass spectrometry was employed. The range of the correlation coefficients of the calibration curves of the analyzed compounds was 0.996-0.999, and the limits of detection and limits of quantification were in the range of 1-2 MUg L(-1) and 3-8 MUg L(-1), respectively. The recovery values for samples spiked at three concentration levels (0.2, 0.5, and 1.0 mg L(-1)) ranged from 87 to 113% with standard deviation not greater than 5.8%. The use of a PVA coated silica capillary allows suppressing the electroosmotic flow and, consequently, increasing of the separation efficiency. The method was successfully used to determine biogenic amines in commercial samples of beer and wine. PMID- 26362808 TI - Optimization of conditions in on-line comprehensive two-dimensional reversed phase liquid chromatography. Experimental comparison with one-dimensional reversed phase liquid chromatography for the separation of peptides. AB - Comprehensive on-line two-dimensional liquid chromatography is an attractive technique to enhance peak capacity and deal with complex samples. Yet, its optimization is not straightforward and requires to take into account a huge number of parameters to finally obtain a good compromise between different criteria which are often conflicting. In this study, we propose a procedure for RPLC*RPLC separations able to define, for a given analysis time, the optimized LC*LC parameters for achieving the best compromise between high peak capacity and low dilution. This procedure makes use of both a prediction tool based on theoretical relationships and a Pareto-optimality approach to optimize these two criteria. The possibility to split the flow-rate of the first dimension before the interface is taken into account as well as the focusing effect in the second dimension. This optimization procedure is applied to the prediction of optimized conditions for the separation of peptides. The need for very short and efficient columns (typically 30 mm as column length and 1.3 MUm as particle diameter) in the second dimension is clearly established whatever the geometry of the first dimension column. Furthermore it is shown that several sets of quite different conditions in the first dimension can lead to similar results and hence that additional quality descriptors are required to make a decision. RPLC*RPLC separations of a protein digest were carried out and the obtained results were found in very good accordance with the predicted ones. Our results were compared to the top results reported in the literature for 1D-RPLC separations of peptides. More than 4-fold increase in peak capacity (5100 vs 1150) at 200 min has been obtained. Furthermore a 40-fold gain in analysis time (1h vs 40 h) was obtained for achieving 1800 as effective peak capacity which is close to the highest peak capacity reported in 1D-RPLC for the separation of peptides. PMID- 26362809 TI - One-pot synthesized functionalized mesoporous silica as a reversed-phase sorbent for solid-phase extraction of endocrine disrupting compounds in milks. AB - A new procedure for the determination of 12 naturally occurring hormones and some related synthetic chemicals in milk, commonly used as growth promoters in cattle, is reported. The method is based on liquid-liquid extraction followed by solid phase extraction (SPE) using a new one-pot synthesized ordered mesoporous silica (of the SBA-15 type) functionalized with octadecyl groups (denoted as SBA-15-C18 CO) as reversed-phase sorbent. The analytes were eluted with methanol and then submitted to HPLC with diode array detection. Under optimal conditions, the method quantification limit for the analytes ranged from 0.023 to 1.36MUg/mL. The sorbent affored the extraction of estrone, 17beta-estradiol, estriol, progesterone, hexestrol, diethylstilbestrol, 4-androstene-3,17-dione, ethinylestradiol, 17alpha-methyltestosterone, nandrolone, prednisolone and testosterone with mean recoveries ranging from 72% to 105% (except for diethylstilbestrol) with RSD<11%. These results were comparable and, in some cases, even better than those obtained with other extraction methods, therefore SBA-15-C18-CO mesoporous silica possess a high potential as a reversed-phase sorbent for SPE of the 12 mentioned endocrine disrupting compounds in milk samples. PMID- 26362810 TI - Online coupling of hydrophilic interaction/strong cation exchange/reversed-phase liquid chromatography with porous graphitic carbon liquid chromatography for simultaneous proteomics and N-glycomics analysis. AB - In this study we developed a fully automated three-dimensional (3D) liquid chromatography methodology-comprising hydrophilic interaction separation as the first dimension, strong cation exchange fractionation as the second dimension, and low-pH reversed-phase (RP) separation as the third dimension-in conjunction downstream with additional complementary porous graphitic carbon separation, to capture non-retained hydrophilic analytes, for both shotgun proteomics and N glycomics analyses. The performance of the 3D system alone was benchmarked through the analysis of the total lysate of Saccharomyces cerevisiae, leading to improved hydrophilic peptide coverage, from which we identified 19% and 24% more proteins and peptides, respectively, relative to those identified from a two dimensional hydrophilic interaction liquid chromatography and low-pH RP chromatography (HILIC-RP) system over the same mass spectrometric acquisition time; consequently, the 3D platform also provided enhanced proteome and protein coverage. When we applied the integrated technology to analyses of the total lysate of primary cerebellar granule neurons, we characterized a total of 2201 proteins and 16,937 unique peptides for this primary cell line, providing one of its most comprehensive datasets. Our new integrated technology also exhibited excellent performance in the first N-glycomics analysis of cynomolgus monkey plasma; we successfully identified 122 proposed N-glycans and 135 N-glycosylation sites from 122 N-glycoproteins, and confirmed the presence of 38 N glycolylneuraminic acid-containing N-glycans, a rare occurrence in human plasma, through tandem mass spectrometry for the first time. PMID- 26362811 TI - Developmental and gender influences on executive function following concussion in youth hockey players. AB - BACKGROUND: Concussion is the most common athletic injury in youth who are simultaneously undergoing rapid developmental changes in the brain, specifically the development of executive functions (EF). The developing brain is more vulnerable to concussive injury with a protracted and different trajectory of recovery than that of adults. Thus, there is a critical need to enhance understanding of how concussion affects EF in youth. OBJECTIVE: To investigate the effects of age, gender and concussion history (i.e. concussion incidence, recency, severity) on EF in youth hockey players. METHODS: This 3-year cross sectional and longitudinal multiple cohort study examined data from 211 hockey players of 8-15 years of age. Mixed-effects modelling was used to examine the influence of age, gender and concussion on EF in youth athletes. FINDINGS: Baseline analyses revealed significant age and gender effects on measures of EF. Multiple effects of concussion history on measures of cognitive flexibility (F = 2.48, p = 0.03) and psychomotor speed (F = 2.59, p = 0.04) were found. IMPLICATIONS: This study highlights the impact of age, gender and concussion on EF in youth. These findings provide foundational knowledge to better manage cognitive sequelae following sports-related concussion. PMID- 26362813 TI - Long-term neuroglobin expression of human astrocytes following brain trauma. AB - Neuroglobin (Ngb), a 17 kDa monomeric protein, was initially described as a vertebrate oxygen-binding heme protein in 2000 and detected in metabolically active organs or cells, like the brain, peripheral nervous system as well as certain endocrine cells. A large array of initial experimental work reported that Ngb displayed a neuron restricted expression pattern in mammalian brains. However, growing evidence indicated astrocytes may also express Ngb under pathological conditions. To address the question whether human astrocytes express Ngb under traumatic insults, we investigated Ngb immuno-reactivity in post-mortem human brain tissues that died of acute, sub-acute and chronic brain trauma, respectively. We observed astrocytic Ngb expression in sub-acute and chronic traumatic brains rather than acute traumatic brains. Strikingly, the Ngb immuno reactive astrocytes were still strongly detectable in groups that died 12 months after brain trauma. Our findings may imply an unexplored role of Ngb in astrocytes and the involved mechanisms were suggested to be further characterized. Also, therapeutic application of Ngb or Ngb-inducible chemical compounds in neuro-genesis or astrocytic scar forming can be expected. PMID- 26362812 TI - All-cause and cause-specific mortality of different migrant populations in Europe. AB - This study aimed to examine differences in all-cause mortality and main causes of death across different migrant and local-born populations living in six European countries. We used data from population and mortality registers from Denmark, England & Wales, France, Netherlands, Scotland, and Spain. We calculated age standardized mortality rates for men and women aged 0-69 years. Country-specific data were pooled to assess weighted mortality rate ratios (MRRs) using Poisson regression. Analyses were stratified by age group, country of destination, and main cause of death. In six countries combined, all-cause mortality was lower for men and women from East Asia (MRRs 0.66; 95 % confidence interval 0.62-0.71 and 0.76; 0.69-0.82, respectively), and Other Latin America (0.44; 0.42-0.46 and 0.56; 0.54-0.59, respectively) than local-born populations. Mortality rates were similar for those from Turkey. All-cause mortality was higher in men and women from North Africa (1.09; 1.08-1.11 and 1.19; 1.17-1.22, respectively) and Eastern Europe (1.30; 1.27-1.33 and 1.05; 1.01-1.08, respectively), and women from Sub Saharan Africa (1.34; 1.30-1.38). The pattern differed by age group and country of destination. Most migrants had higher mortality due to infectious diseases and homicide while cancer mortality and suicide were lower. CVD mortality differed by migrant population. To conclude, mortality patterns varied across migrant populations in European countries. Future research should focus both on migrant populations with favourable and less favourable mortality pattern, in order to understand this heterogeneity and to drive policy at the European level. PMID- 26362814 TI - The habenula and iron metabolism in cerebral mouse models of multiple sclerosis. AB - Iron accumulates in the CNS of patients with multiple sclerosis, but our understanding of the mechanism accounting for this accumulation is unclear. Mouse models of cerebral experimental autoimmune encephalomyelitis (EAE) in C57BL/6 and SJL mice were used together with a histochemical stain for iron and immunohistochemical stains for transferrin receptor, synaptophysin, iron regulatory protein 1 (IRP1) and/or IRP2 to investigate the role of disease activity on CNS iron metabolism. The expression of transferrin receptor, but not IRP1 or IRP2, increased in the medial habenula, which is adjacent to the third ventricle, in response to both types of cerebral EAE. In the habenula, the elevated expression of transferrin receptor in C57BL/6 mice with cerebral EAE was generally restricted to the medial habenula while the expression in SJL mice with cerebral EAE was more diffusely expressed. Iron levels were increased in all regions of the habenula in C57BL/6 mice with cerebral EAE, and in the medial and medial lateral but not the lateral habenula in SJL mice with cerebral EAE. Synaptophysin, which has been observed previously in endocytic vesicles together with the transferrin receptor, was concentrated at the medial habenula, but its levels did not increase with disease in C57BL/6 mice with cerebral EAE. Our results support the model that the medial habenula responds to disease activity by upregulating transferrin receptor to facilitate the movement of iron into the brain from the third ventricle, raising the possibility that a similar mechanism accounts for iron accumulation in deep gray matter structures in patients with multiple sclerosis. PMID- 26362815 TI - Biomarkers for Primary Sjogren's Syndrome. AB - Primary Sjogren's syndrome (pSS) is a systemic autoimmune disease with exocrine gland dysfunction and multi-organ involvement. Recent progress in understanding the pathogenesis of pSS offers an opportunity to find new biomarkers for the diagnosis and assessment of disease activity. Screening noninvasive biomarkers from the saliva and tears has significant potential. The need for specific and sensitive biomarker candidates in pSS is significant. This review aims to summarize recent advances in the identification of biomarkers of Sjogren syndrome, trying to identify reliable, sensitive, and specific biomarkers that can be used to guide treatment decisions. PMID- 26362816 TI - Biomarkers of An Autoimmune Skin Disease--Psoriasis. AB - Psoriasis is one of the most prevalent autoimmune skin diseases. However, its etiology and pathogenesis are still unclear. Over the last decade, omics-based technologies have been extensively utilized for biomarker discovery. As a result, some promising markers for psoriasis have been identified at the genome, transcriptome, proteome, and metabolome level. These discoveries have provided new insights into the underlying molecular mechanisms and signaling pathways in psoriasis pathogenesis. More importantly, some of these markers may prove useful in the diagnosis of psoriasis and in the prediction of disease progression once they have been validated. In this review, we summarize the most recent findings in psoriasis biomarker discovery. In addition, we will discuss several emerging technologies and their potential for novel biomarker discovery and diagnostics for psoriasis. PMID- 26362817 TI - Adipose tissue adaptive response to trans-10,cis-12-conjugated linoleic acid engages alternatively activated M2 macrophages. AB - In mice, nutritional supplementation with the trans-10,cis-12 isomer of linoleic acid (t10,c12-CLA) promotes lipoatrophy, hyperinsulinemia, and macrophage infiltration in white adipose tissue (WAT). We explored the dynamics of these interrelated responses over 2 consecutive 7 d periods of t10,c12-CLA administration and withdrawal. t10,c12-CLA down-regulated lipogenic and lipolytic gene expression and increased collagen deposition, but with no evidence of cross linking. An abundant CD45(+) cell infiltrate, comprising prominently CD206(+)CD11c(-) macrophages, was found in WAT in association with an anti inflammatory gene signature. Infiltration of natural killer (NK) and dendritic cells contributed to WAT's innate immune response to t10,c12-CLA. Less abundant adaptive immune cells colonized WAT, including B, NK T, gammadelta T, and alphabeta T cells. By contrast, T-regulatory cell abundance was not affected. Interruption of treatment allowed recovery of WAT mass and normalization of insulinemia, coincident with regain of WAT homeostasis owing to a coordinated reversion of genic, structural, and immune deregulations. These data revealed a striking resilience of WAT after a short-term metabolic injury induced by t10,c12 CLA, which relies on alternatively activated M2 macrophage engagement. In addition, the temporal links between variations in WAT alterations and insulinemia upon t10,c12-CLA manipulation strengthen the view that WAT dysfunctional status is critically involved in altered glucose homeostasis. PMID- 26362818 TI - Bilateral posterior tibial nerve stimulation for functional anorectal pain--short term outcome. PMID- 26362819 TI - Short-term results of percutaneous treatment of acetabular fractures: functional outcomes, radiographic assessment and complications. AB - PURPOSE: Our purpose was to assess functional outcomes, radiographic characteristics and complications in patients who underwent fixation of acetabular fracture using percutaneous means only. METHODS: This was a retrospective cohort study of adult patients with an acetabular fracture admitted to a level 1 trauma centre and treated with closed reduction and percutaneous fixation. Nineteen patients were identified, and mechanism of injury, radiologic classification of fracture, complications and functional outcomes were analysed. Outcome measurements included Patient Reported Outcomes Measurement Information System (PROMIS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores, which are validated patient questionnaires assessing functional outcome. They are scored as a point range on a per-question basis, with a combined range possibility of 0-96 for WOMAC and 5-75 for PROMIS. RESULTS: Nineteen patients over a two year period were reviewed. Fracture displacement improved following surgery from a mean 7.3 mm (range 0-33 mm) to 2.6 mm (range 0 12 mm). Complications included one post-operative death from non-ST-segment elevation myocardial infarction, sciatic nerve injury, malpositioned screw and deep infection. There were no vascular injuries, pulmonary emboli or deep venous thromboses. Of the 19 patients eligible for the study, seven completed both PROMIS mobility and WOMAC osteoarthritis questionnaires at a mean follow-up of 572 days (1.57 years), with a range of 435-862 days. The average WOMAC score was 7.4 (range 0-30) and mean PROMIS score 66.4 (range 50-75). CONCLUSIONS: Functional outcomes in this study are comparable with other published studies and support percutaneous management of acetabular fractures as an effective alternative to open reduction and internal fixation. PMID- 26362820 TI - High nodal positivity rates even in good clinical responders after chemoradiation of rectal cancer: is organ preservation feasible? AB - AIM: Local excision (LE) is emerging as a treatment option for rectal cancer responding well to chemoradiation. However, it does not address the mesorectal nodal burden. We aimed to identify the factors influencing nodal positivity and subsequently defined a low-risk group by including only patients at low risk. METHOD: A single-centre, retrospective database analysis was carried out of patients with radically resected rectal cancer after neoadjuvant chemoradiation. RESULTS: This study included 524 patients with predominantly low rectal tumours. Nodal positivity among ypT0, T1 and T2 groups was 14.7%, 28% and 30%, respectively. Multivariate analysis with stepwise logistic regression identified the following low-risk features: age >= 40 years, nonsignet ring cell carcinoma (SRCC) histology and pathological complete response (pCR). Sixty-nine patients fulfilling all three criteria were analysed and the nodal positivity was found to be 10.1%, which implies that, if these patients had been selected for LE, one in 10 would have had positive mesorectal nodes. CONCLUSION: Even in patients with low-risk criteria (pCR, non-SRCC histology and age >= 40 years), the residual positive nodal disease burden is 10%. Whether this high incidence of residual nodal disease translates into a similar risk of locoregional recurrence if an organ-preservation strategy is adopted is unclear. PMID- 26362821 TI - Progressive compensatory symbiosis: spouse caregiver experiences of caring for persons with dementia in Taiwan. AB - OBJECTIVES: Spouse caregivers have been the predominant family members who care for persons with dementia in Taiwan. Although studies in western countries have described the caregiving experiences and changes in the marital relationship for these spouse caregivers, this information is lacking in Taiwan. This study explored the experiences of spouse caregivers caring for persons with dementia in Taiwan. METHODS: A grounded theory approach was used for this qualitative descriptive study. Data were collected through recorded in-depth interviews and observations with 15 spouse caregivers of persons with dementia. Constant comparative analysis was used to analyse the transcripts and field notes. RESULTS: Analysis of interview transcripts revealed that the experiences of caregiving for spouse caregivers who lived with persons with dementia could be described as 'progressive compensatory symbiosis.' This core category included three components: awareness of unbalanced intimacy, making a commitment and implementing a compensatory scheme. These experiences could be either mutually beneficial or unbalanced and fluctuated as the disease progressed through the phases of 'subtle,' 'revealed' and 'confirmed,' which also influence the pace, transition and evolution of the compensatory symbiosis. CONCLUSION: This exploratory study describes the family caregiving experiences for 15 spouse caregivers of persons with dementia in Taiwan. These results can provide guidance for developing interventions to prepare, facilitate and promote a mutually beneficial adjustment for spousal caregivers and their spouses as dementia progresses. The findings are worthy of further investigation with a larger sample and a prospective design. PMID- 26362822 TI - Detection and assessment of infectivity of hepatitis E virus in urine. AB - BACKGROUND & AIMS: Hepatitis E virus (HEV) is known to be excreted in the stool but there has been no report of its presence in urine. This study investigated the presence of HEV RNA and antigen (HEV-Ag) in urine and its possible transmission. METHODS: Serum and urine samples from patients with chronic or acute HEV infection and HEV infected monkeys were tested for viral and biochemical markers. Liver and kidney biopsies from the infected monkeys were analyzed by histopathology and immunohistochemistry. The infectivity of HEV from urine was assessed by inoculation into monkeys. RESULTS: HEV RNA and HEV-Ag were detected persistently in the urine of a patient with chronic HEV infection. Subsequently, HEV RNA was detected in the urine of three of the eight (37.5%) acute patients, all of whom had detectable HEV-Ag in their urine. HEV RNA and HEV Ag were also detectable in the urine of HEV infected monkeys. The ratio of HEV-Ag to RNA in the urine of the infected monkeys was significantly higher than in their sera and feces. The parameters of routine urinalysis remained within the normal ranges in the hepatitis E patients and infected monkeys, however, pathological changes and HEV-Ag were observed in the kidneys of the infected monkeys. Furthermore, one of two monkeys became infected with HEV after inoculation with urine from another infected monkey. CONCLUSIONS: HEV infection may result in kidney injury and the urine may pose a risk of transmission. HEV-Ag detection in urine may be valuable for diagnosis of ongoing HEV infection. PMID- 26362823 TI - Protective effect of the multitarget compound DPH-4 on human SSAO/VAP-1 expressing hCMEC/D3 cells under oxygen-glucose deprivation conditions: an in vitro experimental model of cerebral ischaemia. AB - BACKGROUND AND PURPOSE: Stroke and Alzheimer's disease (AD) are related pathologies in which the cerebrovascular system is involved. Plasma levels of semicarbazide-sensitive amine oxidase/vascular adhesion protein 1 (SSAO/VAP-1, also known as Primary Amine Oxidase -PrAO) are increased in both stroke and AD patients and contribute to the vascular damage. During inflammation, its enzymatic activity mediates leukocyte recruitment to the injured tissue, inducing damage in the blood-brain barrier (BBB) and neuronal tissue. We hypothesized that by altering cerebrovascular function, SSAO/VAP-1 might play a role in the stroke AD transition. Therefore, we evaluated the protective effect of the novel multitarget-directed ligand DPH-4, initially designed for AD therapy, on the BBB. EXPERIMENTAL APPROACH: A human microvascular brain endothelial cell line expressing human SSAO/VAP-1 was generated, as the expression of SSAO/VAP-1 is lost in cultured cells. To simulate ischaemic damage, these cells were subjected to oxygen and glucose deprivation (OGD) and re-oxygenation conditions. The protective role of DPH-4 was then evaluated in the presence of methylamine, an SSAO substrate, and/or beta-amyloid (Abeta). KEY RESULTS: Under our conditions, DPH-4 protected brain endothelial cells from OGD and re-oxygenation-induced damage, and also decreased SSAO-dependent leukocyte adhesion. DPH-4 was also effective at preventing the damage induced by OGD and re-oxygenation in the presence of Abeta as a model of AD pathology. CONCLUSIONS AND IMPLICATIONS: From these results, we concluded that the multitarget compound DPH-4 might be of therapeutic benefit to delay the onset and/or progression of the neurological pathologies associated with stroke and AD, which appear to be linked. PMID- 26362824 TI - Volumetric measurement of artificial pure ground-glass nodules at low-dose CT: Comparisons between hybrid iterative reconstruction and filtered back projection. AB - PURPOSE: To compare hybrid iterative reconstruction (HIR) with filtered back projection (FBP) in the volumetry of artificial pure ground-glass nodules (GGNs) with low-dose computed tomography (CT). MATERIALS AND METHODS: Artificial GGNs (10 mm-diameter, 523.6 mm(3), -660 HU) in an anthropomorphic chest phantom were scanned by a 256-row multi-slice CT with three dose levels (10, 30, 100 mAs). Each scan was repeated six times. Each set was reconstructed by FBP and HIR at 0.625-mm thickness. The volumes of artificial GGNs placed at the lung apex and middle lung field of the chest phantom were measured by two observers. Semi automated measurements were performed by clicking the cursor in the center of GGNs, and manual measurements were performed by tracing GGNs on axial section. Modification of the trace was added on a sagittal or coronal section if necessary. Measurement errors were calculated for both the FBP and HIR at each dose level. We used the Wilcoxon signed rank test to identify any significant difference between the measurement errors of the FBP and HIR. Inter-observer, intra-observer, and inter-scan variabilities were evaluated by Bland Altman analysis with limits of agreements given by 95% confidence intervals. RESULTS: There were significant differences in measurement errors only at the lung apex between FBP and HIR with 10 mAs in both the semi-automated (observer 1, -37% vs. 7.2%; observer 2, -39% vs. 1.9%) and manual methods (observer 1, -29% vs. 7.5%; observer 2, -30% vs. 1.1%), respectively (P<0.05). HIR provided each variability equal to or less than one half of that of FBP at 10 mAs in both methods. In the semi-automated method, the inter-observer and intra-observer variabilities obtained by HIR at 10 mAs were -11% to 17% and -6.7% to 6.7%, whereas those for FBP at 10 mAs were -29% to 30% and -38% to 20%, respectively. The inter-scan variability for FBP at 100 mAs vs. HIR at 10 mAs was -9.5% to 11%, and that for FBP at 100 mAs vs. FBP at 10 mAs was -73% to 32%. In the manual method, the inter observer and intra-observer variabilities for HIR at 10 mAs were -14% to 22% and 9.8% to 22%, and those for FBP at 10 mAs were -45% to 36% and -31% to 28%, respectively. The inter-scan variability for FBP at 100 mAs vs. HIR at 10 mAs was -7.4% to 23%, and that for FBP at 100 mAs vs. FBP at 10 mAs was -52% to 26%. CONCLUSION: HIR is superior to FBP in the volumetry of artificial pure GGNs at lung apex with low-dose CT. PMID- 26362825 TI - In vivo monitoring of the inflammatory response in a stented mouse aorta model. AB - The popularity of vascular stents continues to increase for a variety of applications, including coronary, lower limb, renal, carotid, and neurovascular disorders. However, their clinical effectiveness is hindered by numerous postdeployment complications, which may stimulate inflammatory and fibrotic reactions. The purpose of this study was to evaluate the vessel inflammatory response via in vivo imaging in a mouse stent implantation model. Corroded and noncorroded self-expanding miniature nitinol stents were implanted in mice abdominal aortas, and novel in vivo imaging techniques were used to assess trafficking and accumulation of fluorescent donor monocytes as well as cellular proliferation at the implantation site. Monocytes were quantitatively tracked in vivo and found to rapidly clear from circulation within hours after injection. Differences were found between the test groups with respect to the numbers of recruited monocytes and the intensity of the resulting fluorescent signal. Image analysis also revealed a subtle increase in matrix metalloproteinase activity in corroded compared with the normal stented aortas. In conclusion, this study has been successful in developing a murine stent inflammation model and applying novel in vivo imaging tools and methods to monitor the complex biological processes of the host vascular wall response. PMID- 26362826 TI - Controlling type 2 diabetes mellitus with herbal medicines: A triple-blind randomized clinical trial of efficacy and safety. AB - BACKGROUND: The use of alternative medicines is common in patients with diabetes mellitus. The primary aim of the present study was to determine the effects of cinnamon and Caucasian whortleberry (Vaccinium arctostaphylos L.) on blood glucose control, lipid profile and body mass index (BMI) in patients with type 2 diabetes (T2DM). METHODS: In all, 105 T2DM patients were recruited to the present randomized triple-blinded clinical trial. Patients were randomly divided into three groups and administered either placebo, cinnamon or whortleberry supplements (1 g/day) for 90 days. Fasting blood glucose (FBG), serum insulin, lipid profiles, and HbA1c were measured before and after the study. RESULTS: There were no significant differences in baseline characteristics among the three groups. After treatment, FBG, 2-h blood postprandial glucose and homeostasis model assessment of insulin resistance (HOMA-IR) scores were significantly reduced in patients in the whortleberry group, but not in the placebo group. After treatment, there was a significant difference in BMI between the cinnamon and control groups (P = 0.02). There were no significant differences in any variables between the cinnamon and whortleberry groups (P>0.05 for all). In addition, there was a significant decrease in all indices of glucose control in all the cinnamon and whortleberry groups (P < 0.05). CONCLUSIONS: There were no significant differences in blood glucose levels, insulin sensitivity or lipid profile among the three groups. However, the use of cinnamon and whortleberry in addition to conventional medical treatment is recommended to adjust weight and blood glucose levels in patients with T2DM, respectively. PMID- 26362827 TI - The Step approach to Message Design and Testing (SatMDT): A conceptual framework to guide the development and evaluation of persuasive health messages. AB - This paper provides an important and timely overview of a conceptual framework designed to assist with the development of message content, as well as the evaluation, of persuasive health messages. While an earlier version of this framework was presented in a prior publication by the authors in 2009, important refinements to the framework have seen it evolve in recent years, warranting the need for an updated review. This paper outlines the Step approach to Message Design and Testing (or SatMDT) in accordance with the theoretical evidence which underpins, as well as empirical evidence which demonstrates the relevance and feasibility of, each of the framework's steps. The development and testing of the framework have thus far been based exclusively within the road safety advertising context; however, the view expressed herein is that the framework may have broader appeal and application to the health persuasion context. PMID- 26362828 TI - Fascin-1 expression as stratification marker in borderline epithelial tumours of the ovary. AB - AIMS: To evaluate the actin-bundling protein fascin-1 (FSCN1) as marker for borderline ovarian tumours (BOTs). METHODS: We analysed a retrospective cohort of 140 BOTs with validated diagnosis by an independent pathologist. Immunohistochemical detection of FSCN1 was quantified as combined immunoreactive score (CIS) blinded to clinical patient data. Analyses were first performed for FSCN1 positive versus negative, and then verified using three categories derived from the observed distribution (negative, weak, strong; CIS 0, 1-2, 3-9). RESULTS: We detected FSCN1 positivity in 51.4%, and strong expression (CIS 3-9) in 14.3% of the samples. FSCN1 positivity was associated with serous subtype (p<0.001) and micropapillary pattern (p<0.001). Correlation with micropapillary pattern remained significant within the serous BOT (SBOT) subgroup (p=0.022). Strong FSCN1 expression (CIS 3-9) was associated both with the presence of implants (p=0.022), and a higher International Federation of Gynecology and Obstetrics (FIGO) stage (p=0.020). CONCLUSIONS: Our analysis links FSCN1 with SBOT with micropapillary pattern. Strong expression is associated with higher FIGO stage and the presence of implants, both related to elevated risk of recurrence. Hence, FSCN1 is an interesting marker worth further analyses of its prognostic value in BOTs. PMID- 26362829 TI - Nonmedical information seeking amid conflicting health information: negative and positive effects on prostate cancer screening. AB - This study investigates the impact of seeking information about the prostate specific antigen (PSA) test on men's PSA test use during a period of conflicting recommendations. Analyses used longitudinal survey data collected in 2005 and 2006 from a nationally representative sample of U.S. males aged 40-70 years (n = 777). Cross-sectionally, nonmedical information seeking was significantly associated with increased odds of having a PSA test in the past year (Time 1 odds ratio [OR] = 9.74, p < .01, 95% confidence interval [CI] = 4.37, 21.70; Time 2 OR = 5.78, p < .01, 95% CI = 3.17, 10.55). However, lagged analyses showed that among men who had a PSA at Time 1, active seeking is associated with reduced odds of later having a PSA test (OR = 0.33, p < .05, 95% CI = 0.13, 0.85). Participants who had not had a PSA test in the past year very rarely sought information about PSA tests. Information acquisition in an environment of conflicting recommendations may influence adoption of cancer screening behaviors. PMID- 26362830 TI - An analysis of the blood pressure and safety outcomes to renal denervation in African Americans and Non-African Americans in the SYMPLICITY HTN-3 trial. AB - SYMPLICITY HTN-3, the first trial of renal denervation (RDN) versus sham, enrolled 26% African Americans, a prospectively stratified cohort. Although the 6 month systolic blood pressure (SBP) reduction in African Americans (AAs) was similar in the RDN group (-15.5 +/- 25.4 mm Hg, n = 85 vs. -17.8 +/- 29.2, n = 49, P = .641), the sham SBP response was 9.2 mm Hg greater (P = .057) in AAs than non-AAs. In multivariate analyses, sham SBP response was predicted by an interaction between AA and a complex antihypertensive regimen (at least one antihypertensive medication prescribed >=3 times daily), while in the RDN group, SBP response was predicted by an interaction between AA race and baseline BP >= 180 mm Hg. AA race did not independently predict SBP response in either sham or RDN. There appears to be effect modification by race with individual-level patient characteristics in both treatment arms that affect the observed pattern of SBP responses. PMID- 26362833 TI - Bilateral Orbital IgG4-Related Disease with Systemic and Corneal Involvement Showing an Excellent Response to Steroid and Rituximab Therapy: Report of a Case with 11 Years Follow-Up. AB - IgG4-related disease is a newly recognized fibro-inflammatory condition. The purpose of this report is to present a patient with 11 years of follow-up, who revealed characteristic features of IgG4-related disease with systemic, orbital and corneal involvement and showed a favorable response to steroids and rituximab treatment. PMID- 26362832 TI - Characterizing brain tissue by assessment of the distribution of anisotropic microstructural environments in diffusion-compartment imaging (DIAMOND). AB - PURPOSE: To develop a statistical model for the tridimensional diffusion MRI signal at each voxel that describes the signal arising from each tissue compartment in each voxel. THEORY AND METHODS: In prior work, a statistical model of the apparent diffusion coefficient was shown to well-characterize the diffusivity and heterogeneity of the mono-directional diffusion MRI signal. However, this model was unable to characterize the three-dimensional anisotropic diffusion observed in the brain. We introduce a new model that extends the statistical distribution representation to be fully tridimensional, in which apparent diffusion coefficients are extended to be diffusion tensors. The set of compartments present at a voxel is modeled by a finite sum of unimodal continuous distributions of diffusion tensors. Each distribution provides measures of each compartment microstructural diffusivity and heterogeneity. RESULTS: The ability to estimate the tridimensional diffusivity and heterogeneity of multiple fascicles and of free diffusion is demonstrated. CONCLUSION: Our novel tissue model allows for the characterization of the intra-voxel orientational heterogeneity, a prerequisite for accurate tractography while also characterizing the overall tridimensional diffusivity and heterogeneity of each tissue compartment. The model parameters can be estimated from short duration acquisitions. The diffusivity and heterogeneity microstructural parameters may provide novel indicator of the presence of disease or injury. Magn Reson Med 76:963-977, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26362834 TI - Authentication of the origin of sucrose-based sugar products using quantitative natural abundance (13) C NMR. AB - BACKGROUND: Due to possible falsification of sugar cane products with cheaper alternative (sugar beet) on the market, a simple analytical methodology needs to be developed to control the authenticity of sugar products. RESULTS: A direct (13) C nuclear magnetic resonance (NMR) method has been validated to differentiate between sucrose-based sugar products produced from sugar beet (C3 plant) and sugar cane (C4 plant). The method is based on calculating relative (13) C content of the C1, C2, C5, and the C1, C4, C5, C6 positions of the glycosyl and fructosyl moieties of the sucrose molecule, respectively. NMR acquisition parameters and data processing have been optimized to reach a high level of intraday and interday precision (<0.2%). Good linearity (R(2) = 0.93) was obtained for the beet sugar-cane sugar blends containing from 0 to 100 wt% of beet sugar. The method was applied to ten commercial sucrose-based sugar products of different botanical origin. Principal component analysis (PCA) was applied to the relative peak areas for replicate measurements to visualize the difference between studied products. CONCLUSION: The (13) C NMR method is a good alternative to complex isotope ratio mass spectrometry measurements for routine detection and semi-quantification of adulteration of commercial cane sugar (C4 plant) with less expensive beet sugar (C3 plant). (c) 2015 Society of Chemical Industry. PMID- 26362831 TI - Correlations of plasma renin activity and aldosterone concentration with ambulatory blood pressure responses to nebivolol and valsartan, alone and in combination, in hypertension. AB - After demonstration of the antihypertensive efficacy of the combination of the beta-blocker nebivolol and the angiotensin receptor blocker valsartan in an 8 week, randomized, placebo-controlled trial (N = 4161), we now report the effects of this treatment on the renin-angiotensin-aldosterone system in a substudy (n = 805). Plasma renin activity increased with valsartan (54%-73%) and decreased with nebivolol (51%-65%) and the combination treatment (17%-39%). Plasma aldosterone decreased with individual treatments (valsartan, 11%-22%; nebivolol, 20%-26%), with the largest reduction (35%) observed with maximum combination dose (20 mg nebivolol/320 mg valsartan). Baseline ln(plasma renin activity) correlated with the 8-week reductions in 24-hour systolic and diastolic BP following treatments with the combination (all doses combined, P = .003 and P < .001) and nebivolol (both, P < .001), but not with valsartan. Baseline ln(aldosterone) correlated with 24-hour systolic and diastolic BP reductions following combination treatment only (P < .001 and P = .005). The implications of the renin-angiotensin aldosterone system effects of this beta blocker-angiotensin receptor blocker combination should be explored further. PMID- 26362835 TI - Neuroimaging for patient selection for medial temporal lobe epilepsy surgery: Part 1 Structural neuroimaging. AB - The objective of part one of this review is to present the structural neuroimaging techniques that are currently used to evaluate patients with temporal lobe epilepsy (TLE), and to discuss their potential to define patient eligibility for medial temporal lobe surgery. A PubMed query, using Medline and Embase, and subsequent review, was performed for all English language studies published after 1990, reporting neuroimaging methods for the evaluation of patients with TLE. The extracted data included demographic variables, population and study design, imaging methods, gold standard methods, imaging findings, surgical outcomes and conclusions. Overall, 56 papers were reviewed, including a total of 1517 patients. This review highlights the following structural neuroimaging techniques: MRI, diffusion-weighted imaging, tractography, electroencephalography and magnetoencephalography. The developments in neuroimaging during the last decades have led to remarkable improvements in surgical precision, postsurgical outcome, prognosis, and the rate of seizure control in patients with TLE. The use of multiple imaging methods provides improved outcomes, and further improvements will be possible with future studies of larger patient cohorts. PMID- 26362836 TI - Proton tunneling in the A?T Watson-Crick DNA base pair: myth or reality? AB - The results and conclusions reached by Godbeer et al. in their recent work, that proton tunneling in the A?T(WC) Watson-Crick (WC) DNA base pair occurs according to the Lowdin's (L) model, but with a small (~10(-9)) probability were critically analyzed. Here, it was shown that this finding overestimates the possibility of the proton tunneling at the A?T(WC)<->A*?T*(L) tautomerization, because this process cannot be implemented as a chemical reaction. Furthermore, it was outlined those biologically important nucleobase mispairs (A?A*<->A*?A, G?G*< >G*?G, T?T*<->T*?T, C?C*<->C*?C, H?H*<->H*?H (H - hypoxanthine)) - the players in the field of the spontaneous point mutagenesis - where the tunneling of protons is expected and for which the application of the model proposed by Godbeer et al. can be productive. PMID- 26362837 TI - Biophysical and biochemical aspects of antifreeze proteins: Using computational tools to extract atomistic information. AB - Antifreeze proteins (AFPs) are the key biomolecules that protect species from extreme climatic conditions. Studies of AFPs, which are based on recognition of ice plane and structural motifs, have provided vital information that point towards the mechanism responsible for executing antifreeze activity. Importantly, the use of experimental techniques has revealed key information for AFPs, but the exact microscopic details are still not well understood, which limits the application and design of novel antifreeze agents. The present review focuses on the importance of computational tools for investigating (i) molecular properties, (ii) structure-function relationships, and (iii) AFP-ice interactions at atomistic levels. In this context, important details pertaining to the methodological approaches used in molecular dynamics studies of AFPs are also discussed. It is hoped that the information presented herein is helpful for enriching our knowledge of antifreeze properties, which can potentially pave the way for the successful design of novel antifreeze biomolecular agents. PMID- 26362838 TI - Hybrid Russe Procedure for Scaphoid Waist Fracture Nonunion With Deformity. AB - PURPOSE: To assess the results of a hybrid Russe procedure using a corticocancellous strut, cancellous autologous nonvascularized bone graft, and cannulated headless compression screw to reduce the deformity reliably from a collapsed scaphoid nonunion, provide osteoinductive stimulus, and stabilize the fracture for predictable union. METHODS: A hybrid Russe procedure was performed for scaphoid waist fracture nonunions with humpback deformity and no evidence of avascular necrosis. A volar distal radius autologous bone graft was harvested and a strut of cortical bone was fashioned and placed into the nonunion site to restore length and alignment. We packed cancellous bone graft in the remainder of the nonunion site and fixed the scaphoid was with a headless compression screw. Union was determined by radiographs or computed tomography, and intrascaphoid, scapholunate, and radiolunate angles were calculated on final radiographs. We recorded wrist range of motion, grip strength, pinch strength, pain, and complications. RESULTS: Fourteen male and 3 female patients (average age, 32 years; range, 16-78 years), with a mean follow-up of 32 months, were examined clinically and radiographically. All 17 scaphoids united with a mean time for union of 3.6 months. The mean postoperative intrascaphoid angle was significantly reduced from 65 degrees preoperatively to 35 degrees postoperatively. The mean radiolunate angle was significantly improved from 20 degrees from neutral (lunate tilted dorsally) preoperatively to 0 degrees postoperatively. The scapholunate angle also demonstrated significant improvement from 70 degrees preoperatively to 56 degrees postoperatively. Grip strength improved from 70% of the contralateral hand to 89% after the procedure. All patients were satisfied with the functional outcome and no donor site morbidity or hardware issues were identified. CONCLUSIONS: This straightforward hybrid Russe technique predictably restored radiolunate, scapholunate, and intrascaphoid angles with a 100% union incidence. The technique provides excellent functional results in patients with a challenging clinical problem, and we recommend it for scaphoid fracture waist nonunions with dorsal intercalated segment instability deformity. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV. PMID- 26362839 TI - The Effect of Timing on the Treatment and Outcome of Combined Fourth and Fifth Carpometacarpal Fracture Dislocations. AB - PURPOSE: In this study, we designed a prospective project to test the hypothesis that acute fourth and fifth carpometacarpal (CMC) fracture dislocations can be treated conservatively with good restoration of strength, range of motion (ROM), and function, whereas patients with delayed treatment of fourth and fifth CMC fracture dislocations should be treated with open reduction and internal fixation (ORIF). METHODS: We evaluated the results of 20 patients with acute and 6 patients with subacute fourth and fifth CMC fracture dislocations. All 20 acute CMC fracture dislocations were treated conservatively, whereas 3 of the 6 patients with subacute injuries underwent operative intervention. The sensibility, ROM, and grip strength of the hands were tested during 1-year follow up. The Michigan Hand Outcomes Questionnaire and control radiographs were also taken. RESULTS: All 20 patients with acute CMC fracture dislocations showed good restoration of grip strength, ROM, and function, with an average Michigan Hand Outcomes Questionnaire score of 98 +/- 2 at 1-year follow-up. Patients with delayed diagnosis who underwent conservative treatment had noticeable deformity of their injured hands, pain complaints, limited ROM at the fourth and fifth CMC joints, and decreased grip strength. The 3 patients with delayed diagnosis treated with ORIF showed good restoration of grip strength, ROM, and function. CONCLUSIONS: Patients with acute CMC fracture dislocations can be treated by closed reduction with good restoration of grip strength, ROM, and function. In patients with delayed presentation of CMC fracture dislocations, we recommend ORIF. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV. PMID- 26362840 TI - Intermittent Letrozole Administration as Adjuvant Endocrine Therapy for Postmenopausal Women With Hormone Receptor-Positive Early Breast Cancer: A Biologic Study. AB - BACKGROUND: Letrozole withdrawal for 3 months might permit estrogenic stimulation in residual resistant breast cancer disease susceptible to letrozole reintroduction. We investigated the impact of a 3-month letrozole-free interval on serum estradiol levels in patients with early stage breast cancer. PATIENTS AND METHODS: Postmenopausal women with estrogen receptor- and/or progesterone receptor-positive (> 10% of immunoreactive cells), node-negative early breast cancer were eligible. Patients received letrozole for 5 years with a 3-month treatment-free interval after the first year of therapy. The primary end point was to evaluate the increase in serum estradiol levels after a 3-month treatment free interval. The secondary end points were the evaluations of other biologic markers (eg, follicle-stimulating hormone, luteinizing hormone, cholesterol, high density lipoprotein, triglycerides, osteocalcin). RESULTS: From November 2007 to February 2012, 130 evaluable patients were enrolled. The median age was 61 years. Mean values of estradiol levels at time of discontinuation were 5.6 pg/mL (standard deviation 1.7). Estradiol levels increased after a 3-month treatment free interval by a mean of 3.3 pg/mL (66%; P < .0001). Follicle-stimulating hormone and luteinizing hormone levels decreased from baseline by a mean of 7.5 mU/mL (P < .0001), and 1.4 mU/mL (P = .0062), respectively. Triglycerides decreased from baseline by a mean of 8.6 mg/dL (P = .036), and osteocalcin increased by a mean of 2.8 ng/mL (P = .013). CONCLUSION: Intermittent letrozole significantly affects estradiol levels. PMID- 26362841 TI - I-DECIDE: An Online Intervention Drawing on the Psychosocial Readiness Model for Women Experiencing Domestic Violence. AB - BACKGROUND: Domestic violence (DV) perpetrated by men against women is a pervasive global problem with significant physical and emotional consequences. Although some face-to-face interventions in health care settings have shown promise, there are barriers to disclosure to health care practitioners and women may not be ready to access or accept help, reducing uptake. Similar to the mental health field, interventions from clinical practice can be adapted to be delivered by technology. PURPOSE: This article outlines the theoretical and conceptual development of I-DECIDE, an online healthy relationship tool and safety decision aid for women experiencing DV. The article explores the use of the Psychosocial Readiness Model (PRM) as a theoretical framework for the intervention and evaluation. METHODS: This is a theoretical article drawing on current theory and literature around health care and online interventions for DV. RESULTS: The article argues that the Internet as a method of intervention delivery for DV might overcome many of the barriers present in health care settings. Using the PRM as a framework for an online DV intervention may help women on a pathway to safety and well-being for themselves and their children. This hypothesis will be tested in a randomized, controlled trial in 2015/2016. CONCLUSION: This article highlights the importance of using a theoretical model in intervention development and evaluation. PMID- 26362842 TI - Cost analysis of biologic drugs in rheumatoid arthritis first line treatment after methotrexate failure according to patients' body weight. AB - OBJECTIVE: The objective was to assess the influence of patients' weight in the cost of rheumatoid arthritis treatment with biologic drugs used in first line after non-adequate response to methotrexate. PATIENTS AND METHOD: Pharmaceutical and administration costs were calculated in two scenarios: non-optimization and optimization of intravenous (IV) vials. The retrospective analysis of 66 patients from a Spanish 1,000 beds-hospital Rheumatology Clinic Service was used to obtain posology and weight data. The study time horizon was two years. Costs were expressed in 2013 euros. RESULTS: For an average 69kg-weighted patient the lowest cost corresponded to abatacept subcutaneous (SC ABA) (?21,028.09) in the scenario without IV vials optimization and infliximab (IFX) (?20,779.29) with optimization. Considering patients' weight in the scenario without IV vials optimization infliximab (IFX) was the least expensive drug in patients ranged 45 49kg, IV ABA in 50-59kg and SC ABA in patients over 60kg. With IV vials optimization IFX was the least expensive drug in patients under 69kg and SC ABA over 70kg. CONCLUSIONS: Assuming comparable effectiveness of biological drugs, patient's weight is a variable to consider, potentials savings could reach ?20,000 in two years. PMID- 26362843 TI - Diagnostic and therapeutic delay of rheumatoid arthritis and its relationship with health care devices in Catalonia. The AUDIT study. AB - OBJECTIVE: Diagnosis and therapy of patients with early onset rheumatoid arthritis (RA) is influenced by accessibility to specialized care devices. We attempted to analyze the impact of their availability. METHODS: We analyzed time related to diagnosis delay measuring: 1) Time from first clinical symptoms to the first visit with the Rheumatologist; 2) Time from referral to the first visit of Rheumatology; 3) Time between first symptom until final diagnosis; 4) time between first symptom until the initiation of the first disease-modifying antirheumatic drug (DMARD). The presence of these 6 rheumatology devices was defined: 1) early arthritis monographic clinics, 2) RA monographic clinics, 3) Mechanisms for fast programming, 4) Algorithms for referral from primary care (PC), 5) rheumatology consultation services in PC and 6) consulting services in PC. RESULTS: The mean time from onset of symptoms to diagnosis or the establishment of a DMARD in RA patients in Catalonia is very long (11 months). Patients seen in rheumatology devices such as RA monographic clinics, rheumatology consultation in PC and specially in early arthritis clinics are treated early with DMARDs. CONCLUSION: the existence of monographic clinics or consulting in primary care centers is essential to improve early care of RA patients. PMID- 26362844 TI - Matrix metalloproteinase 13-containing exosomes promote nasopharyngeal carcinoma metastasis. AB - Nasopharyngeal cancer (NPC) is an endemic type of head and neck cancer with a high rate of cervical lymph node metastasis. Metastasis is the major cause of death in NPC patients. Increasing evidence indicates that exosomes play a pivotal role in promoting cancer metastasis by enhancing angiogenesis and ECM degradation. Matrix metalloproteinase 13 is an important kind of matrix proteinase that is often overexpressed in various tumors and increases the risk of metastasis. However, little is known about the potential role of MMP13 containing exosomes in NPC. In this study, we found that MMP13 was overexpressed in NPC cells and exosomes purified from conditioned medium (CM) as well as NPC patients' plasma. Transwell analysis revealed that MMP13-containing exosomes facilitated the metastasis of NPC cells. Furthermore, siRNA inhibited the effect of MMP13-containing exosomes on tumor cells metastasis as well as angiogenesis. The current findings provided novel insight into the vital role of MMP13 containing exosomes in NPC progression which might offer unique insights for potential therapeutic strategies for NPC progressions. PMID- 26362845 TI - Assisted dying bill is defeated in House of Commons by 330 to 118 votes. PMID- 26362846 TI - Rosiglitazone activation of PPARgamma-dependent signaling is neuroprotective in mutant huntingtin expressing cells. AB - Peroxisome proliferator-activated receptor gamma (PPARgamma) is a crucial transcription factor for neuroprotection in several brain diseases. Using a mouse model of Huntington's Disease (HD), we recently showed that PPARgamma not only played a major function in preventing HD, but also oral intake of a PPARgamma agonist (thiazolidinedione, TZD) significantly reduced the formation of mutant Huntingtin (mHtt) aggregates in the brain (e.g., cortex and striatum). The molecular mechanisms by which PPARgamma exerts its HD neuroprotective effects remain unresolved. We investigated whether the PPARgamma agonist (rosiglitazone) mediates neuroprotection in the mHtt expressing neuroblastoma cell line (N2A). Here we show that rosiglitazone upregulated the endogenous expression of PPARgamma, its downstream target genes (including PGC1alpha, NRF-1 and Tfam) and mitochondrial function in mHtt expressing N2A cells. Rosiglitazone treatment also significantly reduced mHtt aggregates that included ubiquitin (Ub) and heat shock factor 1 (HSF1), as assessed by a filter-retardation assay, and increased the levels of the functional ubiquitin-proteasome system (UPS), HSF1 and heat shock protein 27/70 (HSP27/70) in N2A cells. Moreover, rosiglitazone treatment normalized endoplasmic reticulum (ER) stress sensors Bip, CHOP and ASK1, and significantly increased N2A cell survival. Taken together, these findings unveil new insights into the mechanisms by which activation of PPARgamma signaling protects against the HD-mediated neuronal impairment. Further, our data also support the concept that PPARgamma may be a novel therapeutic target for treating HD. PMID- 26362847 TI - Association of periodontitis with persistent, pro-atherogenic antibody responses. AB - AIM: To study antibody responses associated with molecular mimicry in periodontitis. MATERIAL & METHODS: Fifty-four periodontitis cases (mean age 54.0 years) and 44 controls (53.6 years) were examined, after which cases received periodontal treatment. Established immunoassays were used to analyse levels of antibodies against two pathogens, Aggregatibacter actinomycetemcomitans (Aa) and Porphyromonas gingivalis (Pg), heat shock proteins (Hsp), Hsp60, Hsp65, and Hsp70, and epitopes of oxidized low-density lipoprotein (oxLDL) (CuOx-LDL and MDA LDL) in plasma samples that were collected at baseline and after 3 (n = 48) and 6 (n = 30) months. RESULTS: When age, sex, smoking habit, and the number of teeth were considered in multivariate logistic regressions, Aa and Pg IgG, Hsp65-IgA, CuOx-LDL-IgG and -IgM, and MDA-LDL-IgG antibody levels were associated with periodontitis, whereas Hsp60-IgG2 antibody levels were inversely associated. The Aa antibody levels significantly correlated with the levels of IgA antibodies to Hsp65 and Hsp70, and both OxLDL IgA antibody levels. The levels of antibodies to Pg correlated with IgG antibodies to Hsp60, Hsp70, and both oxLDL antibody epitopes. None of the antibody levels changed significantly after treatment. CONCLUSIONS: Periodontitis is associated with persistently high levels of circulating antibodies that are reactive with pathogen- and host-derived antigens. PMID- 26362848 TI - Comparative Survival of Patients With Anal Adenocarcinoma, Squamous Cell Carcinoma of the Anus, and Rectal Adenocarcinoma. AB - BACKGROUND: Anal adenocarcinoma (AA) represents 5% to 10% of anal cancer. Little is known about its natural history and prognosis. Using population-based data, we defined the outcomes of AA relative to other anorectal malignancies. PATIENTS AND METHODS: We analyzed the Surveillance, Epidemiology, and End Results 18 database to identify patients >= 18 years old with AA, squamous cell carcinoma of the anus (SCCA), and rectal adenocarcinoma (RA) diagnosed between 1990 and 2011. Median overall survival (OS), 1-year, 3-year, 5-year, and 10-year OS were computed using actuarial methods. The log rank test was used to estimate the difference between Kaplan-Meier survival curves. A Cox proportional hazard regression model was used to adjust the effects of other covariates on survival, including age, year diagnosed, sex, stage, surgery, and radiation. RESULTS: Of 57,369 cases, 0.8% (n = 462) were patients with AA, 87.8% (n = 50,382) were patients with RA, and 11.4% (n = 6525) were patients with SCCA. The median age for AA was 69 years (range, 20 96 years), 66 years (range, 18-103 years) for RA, and 66 years (range, 14-104 years) for SCCA. The median OS was significantly lower for AA (33 months), compared with SCCA (118 months) and RA (68 months) (P < .01). In multivariate analysis, AA had a worse prognosis compared with SCCA (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.59-0.75; P < .01) and RA (HR, 0.68; 95% CI, 0.61 0.77; P < .01), after adjusting for age, sex, race, stage, grade, radiation, and surgery. There was a strong trend for improved survival among patients who received radical surgery (HR, 0.71; 95% CI, 0.51-1.00; P = .05). CONCLUSION: AA confers a significantly worse prognosis than SCCA and RA. PMID- 26362849 TI - Exposure to a farm environment is associated with T helper 1 and regulatory cytokines at age 4.5 years. AB - BACKGROUND: Farm exposure has been shown to protect from childhood asthma and allergic diseases, but underlying immunological mechanisms are not clear yet. OBJECTIVE: To explore whether farming lifestyle determines cytokine profile of peripheral blood mononuclear cells (PBMCs) of 4.5-year-old children (n = 88) from the Finnish PASTURE birth cohort study. METHODS: We analysed regulatory (IL-10, IL-2), T helper 1 (Th1)-associated (IL-12, IFN-gamma), inflammatory (IL-1beta, TNF, CXCL8) and Th2-associated (IL-13) cytokines in unstimulated PBMCs and after a short-term (5 h) stimulation with lipopolysaccharide (LPS). Specific farm exposures (stables, hay barn, farm milk) at age 4 years were assessed from questionnaires. RESULTS: The unstimulated PBMCs of farm children produced more IL 10 (GMR 1.22, P = 0.032), IL-12 (GMR 1.24, P = 0.012) and IFN-gamma (GMR 1.24, P = 0.024) than those of non-farm children. Also, specific farm exposures were associated with higher spontaneous production of cytokines. The number of specific farm exposures tended to be dose dependently associated with higher spontaneous production of IFN-gamma (test for trends, P = 0.013) and lower LPS induced production of TNF (test for trends, P = 0.025). CONCLUSION AND CLINICAL RELEVANCE: Farming lifestyle seemed to be associated with increased spontaneous production of Th1 and regulatory cytokines. Decreased TNF responses to short-term LPS stimulation in farm-exposed children may imply tolerogenic immune mechanisms. These novel findings might contribute to the asthma and allergy protection in farm environment. PMID- 26362850 TI - Hsp90/Cdc37 assembly modulates TGFbeta receptor-II to act as a profibrotic regulator of TGFbeta signaling during cardiac hypertrophy. AB - Cardiac hypertrophy is accompanied by excessive collagen deposition in the heart. Despite painstaking research on this fatal disease, the precise role of molecular chaperones in myocardial fibrosis has not yet been elucidated. In this study, we have analyzed the mechanism by which Heat shock protein 90 (Hsp90)/Cell division cycle 37 (Cdc37) assembly modulates cardiac hypertrophy associated fibrosis. For the in vitro hypertrophy model, Angiotensin II (AngII) treated cultured adult cardiac fibroblasts were used, whereas the in vivo hypertrophy model was generated by renal artery ligation in adult male Wistar rats (Rattus norvegicus). Pretreatment with the Hsp90 inhibitor or the blocking of Hsp90-Cdc37 interactions during pressure overload hypertrophy resulted in ubiquitin-mediated proteasomal degradation of TGFbeta receptor-II (TbetaR-II) leading to termination of TGFbeta mediated signaling. In both cases significant reduction in collagen synthesis was observed revealing the Hsp90/Cdc37 complex as an integral profibrotic component of TGFbeta signaling during cardiac hypertrophy. PMID- 26362851 TI - The Role of Chiropractic Care in the Treatment of Dizziness or Balance Disorders: Analysis of National Health Interview Survey Data. AB - The purpose of this study was to explore the role of chiropractic in the treatment of dizziness or balance disorders through an analysis of data from the 2008 National Health Interview Survey. Odds ratios and 95% confidence intervals (CIs) were used to assess the likelihood that respondents with dizziness or balance problems perceived that they were helped by specified practitioners. Eleven percent of respondents reported having had a balance or dizziness problem; more than 35% were aged 65 years and older. The odds ratio for perceiving being helped by a chiropractor was 4.36 (95% CI, 1.17-16.31) for respondents aged 65 years or older; 9.5 (95% CI, 7.92-11.40) for respondents reporting head or neck trauma; and 13.78 (95% CI, 5.59-33.99) for those reporting neurological or muscular conditions as the cause of their balance or dizziness. PMID- 26362852 TI - The effect of temperature on arson incidence in Toronto, Ontario, Canada. AB - Studies of crime and weather have largely excluded arson from empirical and theoretical consideration, yet weather could influence arson frequency over short time frames, influencing the motivation and activity of potential arsonists, as well as the physical possibility of fire ignition. This study aims to understand the role of weather on urban arson in order to determine its role in explaining short-term variations in arson frequency. We use data reported to the Ontario Fire Marshall's office of arson events in the City of Toronto between 1996 and 2007 to estimate the effect of temperature, precipitation, wind conditions and air pressure on arson events while controlling for the effects of holidays, weekends and other calendar-related events. We find that temperature has an independent association with daily arson frequency, as do precipitation and air pressure. In this study area, cold weather has a larger influence on arson frequency than hot weather. There is also some evidence that extremely hot and cold temperatures may be associated with lower day-time arson frequency, while night-time arson seems to have a simpler positive linear association with temperature. PMID- 26362853 TI - Rock outcrops reduce temperature-induced stress for tropical conifer by decoupling regional climate in the semiarid environment. AB - We aimed to understand the effect of rock outcrops on the growth of Podocarpus lambertii within a microrefuge. Our hypothesis holds that the growth and survival of this species depend on the regional climate decoupling provided by rock outcrops. To test this hypothesis, we characterized the microclimate of (1) surrounding vegetation, (2) rock outcrop corridors, and (3) adjacencies. We assessed population structure by collecting data of specimen stem diameter and height. We also assessed differences between vegetation associated or not with outcrops using satellite imaging. For dendrochronological analyses, we sampled 42 individuals. Tree rings of 31 individuals were dated, and climate-growth relationships were tested. Rock outcrops produce a favorable microclimate by reducing average temperature by 4.9 degrees C and increasing average air humidity by 12 %. They also reduce the variability of atmospheric temperature by 42 % and air humidity by 20 % supporting a vegetation with higher leaf area index. Within this vegetation, specimen height was strongly constrained by the outcrop height. Although temperature and precipitation modulate this species growth, temperature-induced stress is the key limiting growth factor for this population of P. lambertii. We conclude that this species growth and survival depend on the presence of rock outcrops. These topography elements decouple regional climate in a favorable way for this species growth. However, these benefits are restricted to the areas sheltered by rock outcrops. Although this microrefuge supported P. lambertii growth so far, it is unclear whether this protection would be sufficient to withstand the stress of future climate changes. PMID- 26362854 TI - Erratum to: Estimating the Differential Costs of Criminal Activity for Juvenile Drug Court Participants: Challenges and Recommendations. PMID- 26362855 TI - The Relevance of Social Theory in the Practice of Environmental Management. AB - In this paper I argue that the dominance of certain paradigms and theories on policies can have an influence on the value added by impact assessments. A link exists between paradigms and theories and policies and consequently the practices humans develop to tackle real world problems. I also argue that different types of thinking (contained in paradigms and theories) need to be integrated, at least at the scientific level, to enhance our understanding of social phenomena. This in turn can have a positive influence on policy processes that follow impact assessment recommendations. I am not arguing for the adoption of theoretical positions by practitioners, Instead, I contend that if impact assessments are informed by a variety of paradigms and theories, the policy practitioner might have a better understanding of the issue and the moral choices he or she needs to make. I will highlight the connection between theory and policies with practical examples from the social impact assessment of the De Hoop Dam, which was constructed on the Steelpoort River. I also argue for an integration of different theories to give a deeper understanding of real world problems. PMID- 26362857 TI - Erratum to: Infusion of donor lymphocytes expressing the herpes simplex virus thymidine kinase suicide gene for recurrent hematologic malignancies after allogeneic hematopoietic stem cell transplantation. PMID- 26362856 TI - Risk factors associated with mortality in patients infected with influenza A/H1N1 in Mexico. AB - BACKGROUND: Influenza virus pandemics vary dramatically in their severity and mortality. Thus, it is very important to identify populations with high risks of developing severe illness to reduce mortality in future pandemics. The purpose was to determine the mortality-associated risk factors in hospitalized Mexican patients infected with influenza A/H1N1. RESULTS: The risk factors associated with mortality were: male sex [odds ratio (OR) = 5.25, confidence interval (CI) = 1.22-28.95], medical attention delayed >3 days (OR = 9.9, CI = 1.51-64.52), anti flu therapy delayed >3 days (OR = 10.0, CI = 1.07-93.43), admission to intensive care unit (ICU) (OR = 9.9, CI = 1.51-64.52) and creatinine levels >1.0 mg/dL when admitted to hospital (OR = 11.2, CI = 1.05-120.32). After adjusting for the effects of potentially confounding variables in a logistic regression model, delayed medical attention (OR = 13.91, CI = 1.09-41.42, p = 0.044) and ICU hospitalization (OR = 11.02, CI = 1.59-76.25, p = 0.015) were the only predictors of mortality. CONCLUSION: Early medical attention is essential for reducing the mortality risk in patients with influenza A/H1N1, while a requirement for ICU management increases the risk. PMID- 26362858 TI - Rapamycin restores p14, p15 and p57 expression and inhibits the mTOR/p70S6K pathway in acute lymphoblastic leukemia cells. AB - The aim of the present study was to investigate the effects of rapamycin and its underlying mechanisms on acute lymphoblastic leukemia (ALL) cells. We found that the p14, p15, and p57 genes were not expressed in ALL cell lines (Molt-4 and Nalm 6) and adult ALL patients, whereas mTOR, 4E-BP1, and p70S6K were highly expressed. In Molt-4 and Nalm-6 cells exposed to rapamycin, cell viability decreased and the cell cycle was arrested at the G1/S phase. Rapamycin restored p14, p15, and p57 gene expression through demethylation of the promoters of these genes. As expected, rapamycin also increased p14 and p15 protein expression in both Molt-4 and Nalm-6 cells, as well as p57 protein expression in Nalm-6 cells. Rapamycin additionally decreased mTOR and p70S6K mRNA levels, as well as p70S6K and p-p70S6K protein levels. However, depletion of mTOR by siRNA did not alter the expression and promoter methylation states of p14, p15, and p57. These results indicate that the inhibitory effect of rapamycin may be due mainly to increased p14, p15, and p57 expression via promoter demethylation and decreased mTOR and p70S6K expression in ALL cell lines. These results suggest a potential role for rapamycin in the treatment of adult ALL. PMID- 26362859 TI - iNOS affects matrix production in distal lung fibroblasts from patients with mild asthma. AB - INTRODUCTION: A high level of exhaled nitric oxide (NO) is a marker for inflammation in the airways of asthmatic subjects. However, little is known about how NO and inducible nitric oxides synthase (iNOS) activity may affect remodelling in the distal lung. We hypothesized that there is a link between iNOS and ongoing remodelling processes in the distal lung of mild asthmatics. METHODS: Patients with mild asthma (n = 6) and healthy control subjects (n = 8) were included. Exhaled NO was measured at different flow rates and alveolar NO concentrations were calculated. For studies of remodelling processes in the distal lung, primary fibroblasts were grown from transbronchial biopsies and stimulated with unselective and selective NOS inhibitors or a NO donor. The mRNA expression of iNOS and synthesis of NO (indirectly as nitrite/nitrate) were measured and distal lung fibroblast synthesis of the extracellular matrix proteoglycans were analysed. RESULTS: The distal lung fibroblasts expressed iNOS, and there was a tendency of higher expression in fibroblasts from patients with asthma. The selective iNOS inhibitor 1400 W inhibited iNOS expression and NO synthesis in fibroblasts from patients with asthma (p = 0.031). Treatment with 1400 W significantly increased synthesis of the proteoglycan versican (p = 0.018) in distal fibroblasts from patients with asthma whereas there were no effects in fibroblasts from control subjects. CONCLUSIONS: Our data suggest that there is a link between iNOS and remodelling in the distal lung of subjects with mild asthma and that iNOS could have a modulatory role in pathological airway remodelling. PMID- 26362860 TI - Cross-reactivity of commercially available anti-human monoclonal antibodies with canine cytokines: establishment of a reliable panel to detect the functional profile of peripheral blood lymphocytes by intracytoplasmic staining. AB - BACKGROUND: The process for obtaining monoclonal antibodies against a specific antigen is very laborious, involves sophisticated technologies and it is not available in most research laboratories. Considering that most cytokines remain partially conserved among species during evolution, the search for antibody cross reactivity is an important strategy for immunological studies in veterinary medicine. In this context, the amino acid sequence from human and canine cytokines have demonstrated 49-96 % homology, suggesting high probability of cross-reactivity amongst monoclonal antibodies. For this, 17 commercially available anti-human monoclonal antibodies [IL-1alpha, IL-1beta, IL-2, IL-4, IL 5, IL-6, IL-8 (#1, #2), IL-10, IL-12, IL-13, IL-17A, IFN-gamma (#1, #2), TNF alpha (#1, #2) and TGF-beta], were evaluated in vitro for intracellular cytokine detection in a stimulated canine blood culture by flow cytometry and confocal microscopy. Lymphocytes from peripheral blood of healthy and two unhealthy dogs were analyzed. RESULTS: Eleven anti-human mAbs [IL-1alpha, IL-4, IL-5, IL-6, IL-8 (#1, #2), IL-12, IL-17A, TNF-alpha (#1, #2) and TGF-beta] cross-reacted against canine intracellular cytokines. The specificity of the assays was not affected after Fc-blocking. Three anti-human cytokine mAbs [IL-4, IL-8 (#2) and TGF-beta] when evaluated by confocal microscopy also cross-reacted with intracellular canine cytokines. The identification of human mAbs that cross-reacted with canine cytokines may support their use as immunological biomarkers in veterinary medicine studies. CONCLUSION: The identification of these 11 anti-human cytokine mAbs that cross-reacted with canine cytokines will be useful immunological biomarkers for pathological conditions by flow cytometry and fluorescence microscopy in dogs. PMID- 26362862 TI - Long-term ambient air pollution exposure and risk of high blood pressure among citizens in Nis, Serbia. AB - Epidemiological studies suggest that long-term exposure to air pollution increases the risk for high blood pressure (BP). The aim of our study is to evaluate any effects in BP in citizens exposed to long-term ambient air pollution. The subjects are 1136 citizens, aged 18-70 years, living for more than 5 years in the same home in the areas with a different level of air pollution. The air concentrations of black smoke and sulfur dioxide were determined in the period from 2001 to 2011. We measured systolic and diastolic BP and heart rate. Multivariate methods were used in the analysis. Alcohol consumption had the greatest influence on the incidence of hypertension as a risk factor (RR: 3.461; 95% CI: 1.72-6.93) and age had the least (RR: 1.23; 95% CI: 1.183-1.92). Exposure to air pollution increases risk for developing hypertension 2.5 times (95% CI: 1.46-4.49). Physical activity has proved to be statistically significant protective factor for the development of hypertension. Long-term exposure to low levels of main air pollutants is significantly associated with elevated risk of hypertension. PMID- 26362861 TI - Parental urinary biomarkers of preconception exposure to bisphenol A and phthalates in relation to birth outcomes. AB - BACKGROUND: Bisphenol A (BPA) and phthalates are ubiquitous non-persistent endocrine disrupting chemicals whose relation with infant birth size is not clearly understood. METHODS: We examined associations between maternal and paternal preconception urinary concentrations of total BPA and 14 phthalate metabolites and birth size for 233 infants. Multiple linear regression models were used to estimate parental quartiles of BPA and phthalates in relation to birth weight, length, head circumference, and ponderal index with separate models run for each parent adjusting for age, smoking, body mass index, education, alcohol, parity, and creatinine. Models also included an interaction term for each chemical and infant sex and were further adjusted to include the other partner's chemical concentrations. RESULTS: In maternal models adjusted for partner's exposure and covariates, reductions in birth weight (range: 178-215 g; p < 0.05) were observed for the 2nd quartile of maternal monomethyl phthalate, mono-[(2-carboxymethyl) hexyl] phthalate and mono-n-octyl phthalate when compared with the 1st quartiles. The 3rd quartile of monoethylhexyl phthalate (mEHP) was also associated with a 200.16 g (95 % CI: -386.90, -13.42) reduction. Similar reductions in birth weight were observed for the 2(nd) quartile of paternal mEHP (beta = -191.93 g; 95 % CI: -381.61, -2.25). Additionally, select maternal urinary metabolites were associated with decreased head circumference, birth length and gestational age. However, paternal concentrations were generally associated with increased birth length and gestational age. CONCLUSIONS: We observed some suggestion that preconception maternal and paternal urinary concentration of BPA and specific phthalate metabolites may be associated with smaller birth size and increased gestational age, though the findings appeared to be parent and chemical specific. PMID- 26362863 TI - Associations between high callous-unemotional traits and quality of life across youths with non-conduct disorder diagnoses. AB - Research regarding callous-unemotional (CU) traits in non-conduct disorder (CD) diagnoses is sparse. We investigated the presence of high CU traits and their associations with quality of life (QoL) in a clinically referred sample of youths with non-CD diagnoses. Parents of 1018 children referred to a child and adolescent psychiatric clinic and rated their child's CU traits and QoL. Experienced clinicians derived DSM-IV-TR diagnoses based on systematic clinical evaluations of these children. High CU traits compared to low CU traits were present in 38.5 % of the sample, and more often in boys than girls (69.4 vs. 30.6 %, p = .004), and were associated with more police contacts (12.2 vs. 3.5 %, p < .001). Logistic regression analyses revealed that those with diagnoses of autism spectrum disorder (odds ratio; OR = 1.61; 95 % CI 1.24-2.09; p < .001) and disruptive behavior disorder not otherwise specified/oppositional defiant disorder (OR = 4.98; 95 % CI 2.93-8.64; p < .001), but not attention deficit/hyperactivity disorder (OR = 1.01; 95 % CI .79-1.31; p = .94), were more likely to have high than low CU traits. Those with anxiety/mood disorders were more likely to have low than high CU traits (OR = .59; 95 % CI .42-82; p = .002). In all diagnostic groups, high CU compared to low CU traits were associated with significantly lower QoL, while controlling for gender, age, and comorbidity. As such, high CU traits significantly modify QoL in non-CD disorders. PMID- 26362864 TI - Sepsis-associated pulmonary complications in emergency department patients monitored with serial lactate: An observational cohort study. AB - PURPOSE: Patients with severe sepsis and septic shock are at high risk for development of pulmonary complications, including acute respiratory distress syndrome (ARDS). Serial lactate monitoring is a useful tool to gauge global tissue hypoxia in emergency department (ED) patients with sepsis. We hypothesized that patients undergoing serial lactate monitoring (SL) would demonstrate a decreased incidence of pulmonary complications. METHODS: This is a retrospective observational cohort study of adult severe sepsis and septic shock patients with elevated lactate presenting to a large academic ED. A total of 243 patients were assigned to SL (n=132) or no serial lactate monitoring (NL; n=111). The primary outcome was a composite of pulmonary complications: (1) ARDS development and (2) respiratory failure. RESULTS: Twenty-eight patients (21%) in the SL group and 37 patients (33%) in the NL group developed the primary outcome (P=.03). Multivariate analysis demonstrated an association between the NL group and development of pulmonary complications (adjusted odds ratio [aOR], 2.1; confidence interval [CI], 1.15-3.78). Emergency department mechanical ventilation was independently associated with development of ARDS (aOR, 3.5; 1.8-7.0). In the a priori subgroup of patients mechanically ventilated in the ED (n=97), those who developed ARDS received higher tidal volumes compared to patients who did not develop ARDS (8.7 mL/kg predicted body weight [interquartile range, 7.6-9.5] vs 7.6 [interquartile range, 6.8-9.0]; P<.01). CONCLUSIONS: Serial lactate monitoring is associated with a decrease in major pulmonary complications in severe sepsis and septic shock. Acute respiratory distress syndrome incidence is also influenced by ED-based mechanical ventilation. These results provide 2 potentially modifiable variables to be targeted in future studies to prevent pulmonary complications in this patient subset. PMID- 26362865 TI - Heterozygous inactivation of plasma membrane Ca(2+)-ATPase in mice increases glucose-induced insulin release and beta cell proliferation, mass and viability. AB - AIMS/HYPOTHESIS: Calcium plays an important role in the process of glucose induced insulin release in pancreatic beta cells. These cells are equipped with a double system responsible for Ca(2+) extrusion--the Na/Ca exchanger (NCX) and the plasma membrane Ca(2+)-ATPase (PMCA). We have shown that heterozygous inactivation of NCX1 in mice increased glucose-induced insulin release and stimulated beta cell proliferation and mass. In the present study, we examined the effects of heterozygous inactivation of the PMCA on beta cell function. METHODS: Biological and morphological methods (Ca(2+) imaging, Ca(2+) uptake, glucose metabolism, insulin release and immunohistochemistry) were used to assess beta cell function and proliferation in Pmca2 (also known as Atp2b2) heterozygous mice and control littermates ex vivo. Blood glucose and insulin levels were also measured to assess glucose metabolism in vivo. RESULTS: Pmca (isoform 2) heterozygous inactivation increased intracellular Ca(2+) stores and glucose induced insulin release. Moreover, increased beta cell proliferation, mass, viability and islet size were observed in Pmca2 heterozygous mice. However, no differences in beta cell glucose metabolism, proinsulin immunostaining and insulin content were observed. CONCLUSIONS/INTERPRETATION: The present data indicates that inhibition of Ca(2+) extrusion from the beta cell and its subsequent intracellular accumulation stimulates beta cell function, proliferation and mass. This is in agreement with our previous results observed in mice displaying heterozygous inactivation of NCX, and indicates that inhibition of Ca(2+) extrusion mechanisms by small molecules in beta cells may represent a new approach in the treatment of type 1 and type 2 diabetes. PMID- 26362866 TI - Bradyrhizobium tropiciagri sp. nov. and Bradyrhizobium embrapense sp. nov., nitrogen-fixing symbionts of tropical forage legumes. AB - Biological nitrogen fixation is a key process for agricultural production and environmental sustainability, but there are comparatively few studies of symbionts of tropical pasture legumes, as well as few described species of the genus Bradyrhizobium, although it is the predominant rhizobial genus in the tropics. A detailed polyphasic study was conducted with two strains of the genus Bradyrhizobium used in commercial inoculants for tropical pastures in Brazil, CNPSo 1112T, isolated from perennial soybean (Neonotonia wightii), and CNPSo 2833T, from desmodium (Desmodium heterocarpon). Based on 16S-rRNA gene phylogeny, both strains were grouped in the Bradyrhizobium elkanii superclade, but were not clearly clustered with any known species. Multilocus sequence analysis of three (glnII, gyrB and recA) and five (plus atpD and dnaK) housekeeping genes confirmed that the strains are positioned in two distinct clades. Comparison with intergenic transcribed spacer sequences of type strains of described species of the genus Bradyrhizobium showed similarity lower than 93.1 %, and differences were confirmed by BOX-PCR analysis. Nucleotide identity of three housekeeping genes with type strains of described species ranged from 88.1 to 96.2 %. Average nucleotide identity of genome sequences showed values below the threshold for distinct species of the genus Bradyrhizobium ( < 90.6 %), and the value between the two strains was also below this threshold (91.2 %). Analysis of nifH and nodC gene sequences positioned the two strains in a clade distinct from other species of the genus Bradyrhizobium. Morphophysiological, genotypic and genomic data supported the description of two novel species in the genus Bradyrhizobium, Bradyrhizobium tropiciagri sp. nov. (type strain CNPSo 1112T = SMS 303T = BR 1009T = SEMIA 6148T = LMG 28867T) and Bradyrhizobium embrapense sp. nov. (type strain CNPSo 2833T = CIAT 2372T = BR 2212T = SEMIA 6208T = U674T = LMG 2987). PMID- 26362867 TI - Quality target negotiation in health care: evidence from the English NHS. AB - We examine how public sector third-party purchasers and hospitals negotiate quality targets when a fixed proportion of hospital revenue is required to be linked to quality. We develop a bargaining model linking the number of quality targets to purchaser and hospital characteristics. Using data extracted from 153 contracts for acute hospital services in England in 2010/2011, we find that the number of quality targets is associated with the purchaser's population health and its budget, the hospital type, whether the purchaser delegated negotiation to an agency, and the quality targets imposed by the supervising regional health authority. PMID- 26362868 TI - The regulation of ER export and Golgi retention of ST3Gal5 (GM3/GM4 synthase) and B4GalNAcT1 (GM2/GD2/GA2 synthase) by arginine/lysine-based motif adjacent to the transmembrane domain. AB - In the Golgi maturation model, the Golgi cisternae dynamically mature along a secretory pathway. In this dynamic process, glycosyltransferases are transported from the endoplasmic reticulum (ER) to the Golgi apparatus where they remain and function. The precise mechanism behind this maturation process remains unclear. We investigated two glycosyltransferases, ST3Gal5 (ST3G5) and B4GalNAcT1 (B4GN1), involved in ganglioside synthesis and examined their signal sequences for ER export and Golgi retention. Reports have suggested that the [R/K](X)[R/K] motif functions as an ER exporting signal; however, this signal sequence is insufficient in stably expressed, full-length ST3G5. Through further analysis, we have clarified that the (2)R(3)R(X)(5) (9)K(X)(3) (13)K sequence in ST3G5 is essential for ER export. We have named the sequence the R/K-based motif. On the other hand, for ER export of B4GN1, the homodimer formation in addition to the R/K-based motif is required for ER export suggesting the importance of unidentified lumenal side interaction. We found that ST3G5 R2A/R3A and K9A/K13A mutants localized not only in Golgi apparatus but also in endosomes. Furthermore, the amounts of mature type asparagine-linked (N)-glycans in ST3G5 R2A/R3A and K9A/K13A mutants were decreased compared with those in wild-type proteins, and the stability of the mutants was lower. These results suggest that the R/K-based motif is necessary for the Golgi retention of ST3G5 and that the retention is involved in the maturation of N-glycans and in stability. Thus, several basic amino acids located on the cytoplasmic tail of ST3G5 play important roles in both ER export and Golgi retention. PMID- 26362869 TI - Cloning and expression of 3-deoxy-d-manno-oct-2-ulosonic acid alpha-ketoside hydrolase from oyster hepatopancreas?. AB - We have previously reported that oyster hepatopancreas contained three unusual alpha-ketoside hydrolases: (i) a 3-deoxy-d-manno-oct-2-ulosonic acid alpha ketoside hydrolase (alpha-Kdo-ase), (ii) a 3-deoxy-D-glycero-D-galacto-non-2 ulosonic acid alpha-ketoside hydrolase and (iii) a bifunctional ketoside hydrolase capable of cleaving both the alpha-ketosides of Kdn and Neu5Ac (Kdn sialidase). After completing the purification of Kdn-sialidase, we proceeded to clone the gene encoding this enzyme. Unexpectedly, we found that instead of expressing Kdn-sialidase, our cloned gene expressed alpha-Kdo-ase activity. The full-length gene, consisting of 1176-bp (392 amino acids, Mr 44,604), expressed an active recombinant alpha-Kdo-ase (R-alpha-Kdo-ase) in yeast and CHO-S cells, but not in various Escherichia coli strains. The deduced amino acid sequence contains two Asp boxes (S(277)PDDGKTW and S(328)TDQGKTW) commonly found in sialidases, but is devoid of the signature FRIP-motif of sialidase. The R-alpha Kdo-ase effectively hydrolyzed the Kdo in the core-oligosaccharide of the structurally defined lipopolysaccharide (LPS), Re-LPS (Kdo(2)-Lipid A) from Salmonella minnesota R595 and E. coli D31m4. However, Rd-LPS from S. minnesota R7 that contained an extra outer core phosphorylated heptose was only slowly hydrolyzed. The complex type LPS from Neisseria meningitides A1 and M992 that contained extra 5-6 sugar units at the outer core were refractory to R-alpha-Kdo ase. This R-alpha-Kdo-ase should become useful for studying the structure and function of Kdo-containing glycans. PMID- 26362870 TI - The clastogenicity of 4NQO is cell-type dependent and linked to cytotoxicity, length of exposure and p53 proficiency. AB - 4-Nitroquinoline 1-oxide (4NQO) is used as a positive control in various genotoxicity assays because of its known mutagenic and carcinogenic properties. The chemical is converted into 4-hydroxyaminoquinoline 1-oxide and gives rise to three main DNA adducts, N-(deoxyguanosin-8-yl)-4AQO, 3-(desoxyguanosin-N (2)-yl) 4AQO and 3-(deoxyadenosin-N (6)-yl)-4AQO. This study was designed to assess the shape of the dose-response curve at low concentrations of 4NQO in three human lymphoblastoid cell lines, MCL-5, AHH-1 and TK6 as well as the mouse lymphoma L5178Y cell line in vitro. Chromosomal damage was investigated using the in vitro micronucleus assay, while further gene mutation and DNA damage studies were carried out using the hypoxanthine-guanine phosphoribosyltransferase forward mutation and comet assays. 4NQO showed little to no significant increases in micronucleus induction in the human lymphoblastoid cell lines, even up to 55+/-5% toxicity. A dose-response relationship could only be observed in the mouse lymphoma cell line L5178Y after 4NQO treatment, even at concentrations with no reduction in cell viability. Further significant increases in gene mutation and DNA damage induction were observed. Hence, 4NQO is a more effective point mutagen than clastogen, and its suitability as a positive control for genotoxicity testing has to be evaluated for every individual assay. PMID- 26362871 TI - Validation of coding algorithms for the identification of patients hospitalized for alcoholic hepatitis using administrative data. AB - BACKGROUND: Epidemiologic studies of alcoholic hepatitis (AH) have been hindered by the lack of a validated International Classification of Disease (ICD) coding algorithm for use with administrative data. Our objective was to validate coding algorithms for AH using a hospitalization database. METHODS: The Hospital Discharge Abstract Database (DAD) was used to identify consecutive adults (>=18 years) hospitalized in the Calgary region with a diagnosis code for AH (ICD-10, K70.1) between 01/2008 and 08/2012. Medical records were reviewed to confirm the diagnosis of AH, defined as a history of heavy alcohol consumption, elevated AST and/or ALT (<300 U/L), serum bilirubin >34 MUmol/L, and elevated INR. Subgroup analyses were performed according to the diagnosis field in which the code was recorded (primary vs. secondary) and AH severity. Algorithms that incorporated ICD-10 codes for cirrhosis and its complications were also examined. RESULTS: Of 228 potential AH cases, 122 patients had confirmed AH, corresponding to a positive predictive value (PPV) of 54% (95% CI 47-60%). PPV improved when AH was the primary versus a secondary diagnosis (67% vs. 21%; P < 0.001). Algorithms that included diagnosis codes for ascites (PPV 75%; 95% CI 63-86%), cirrhosis (PPV 60%; 47-73%), and gastrointestinal hemorrhage (PPV 62%; 51-73%) had improved performance, however, the prevalence of these diagnoses in confirmed AH cases was low (29-39%). CONCLUSIONS: In conclusion the low PPV of the diagnosis code for AH suggests that caution is necessary if this hospitalization database is used in large-scale epidemiologic studies of this condition. PMID- 26362872 TI - Barriers and Challenges of Cancer Patients and Their Experience with Patient Navigators in the Rural US/Mexico Border Region. AB - Patient navigation is a widely used approach to minimize health disparities among socioeconomically marginalized cancer patients. Although patient navigation is widely used, there is a dearth of studies exploring patient experience with navigators among rural cancer patients. This qualitative study explores the challenges and barriers to cancer care faced by cancer patients living in a US/Mexico border region in Southern California. We individually interviewed 22 cancer patients, most of whom were Latino. Data were analyzed using constant comparison with a reiterative analysis method. The main themes relating to barriers to care and experiences with patient navigators include the following: (1) removing financial barriers, (2) coordinating services, and (3) providing therapeutic interventions. The cancer patients highly valued the navigators for their knowledge about community resources, support, and advocacy. This study suggests that it is imperative that navigators know the regional and binational health care utilization issues that impact patients' access to cancer care. PMID- 26362873 TI - Behavioral Correlates of Prioritizing Popularity in Adolescence. AB - Little is known about individual differences in adolescents' motivation to achieve and maintain popularity. This study examined the moderating effects of prioritizing popularity on the associations between popularity and adjustment outcomes in late adolescence. Participants were 314 Dutch eleventh-grade students (M age = 16.83 years; 52 % male) who completed measures of popularity, prioritizing popularity, and prosocial, antisocial, and risk behaviors. It was hypothesized that associations between popularity and adjustment outcomes are stronger for adolescents who prioritize popularity. The results indicate that the combination of being popular and valuing popularity was strongly related to antisocial and risk behaviors, but not to prosocial behaviors. Adolescents' social status motivations thus play an important role in the association of popularity with antisocial and risk behaviors in late adolescence. PMID- 26362875 TI - Dose correction for post-contrast T1 mapping of the heart: the MESA study. AB - Post-contrast myocardial T1 (T1(myo,c)) values have been shown to be sensitive to myocardial fibrosis. Recent studies have shown differences in results obtained from T1(myo,c) and extracellular volume fraction (ECV) with respect to percentage fibrosis. By exploring the relationship between blood plasma volume and T1(myo,c), the underlying basis for the divergence can be explained. Furthermore, dose administration based on body mass index (BMI), age and gender can mitigate the divergence in results. Inter-subject comparison of T1(myo,c) required adjustment for dose (in mmol/kg), time and glomerular filtration rate. Further adjustment for effective dose based on lean muscle mass reflected by blood/plasma volume was performed. A test case of 605 subjects from the MESA study who had undergone pre- and post-contrast T1 mapping was studied. T1(myo,c) values were compared between subjects with and without metabolic syndrome (MetS), between smoking and non-smoking subjects, and subjects with and without impaired glucose tolerance, before and after dose adjustment based on plasma volume. Comparison with ECV (which is dose independent), pre-contrast myocardial T1 and blood normalized myocardial T1 values was also performed to validate the correction. There were significant differences in T1(myo,c) (post plasma volume correction) and ECV between current and former smokers (p value 0.017 and 0.01, respectively) but not T1(myo,c) prior to correction (p = 0.12). Prior to dose adjustment for plasma volume, p value was <0.001 for T1(myo,c) between MetS and non-MetS groups and was 0.13 between subjects with and without glucose intolerance; after adjustment for PV, p value was 0.63 and 0.99. Corresponding ECV p values were 0.44 and 0.99, respectively. Overall, ECV results showed the best agreement with PV corrected T1(myo,c) (mean absolute difference in p values = 0.073) and pre contrast myocardial T1 in comparison with other measures (T1(myo,c( prior to correction, blood/plasma T1 value normalized myocardium). Weight-based contrast dosing administered in mmol/kg results in a bias in T1 values which can lead to erroneous conclusions. After adjustment for lean muscle mass based on plasma volume, results from T1(myo,c) were in line with ECV derived results. Furthermore, the use of a modified equivalent dose adjusted for BMI, age, sex and hematocrit can be adopted for quantitative imaging. PMID- 26362874 TI - Acute ischemic stroke imaging: a practical approach for diagnosis and triage. AB - Ischemic stroke is a prevalent disease with significant associated morbidity and healthcare costs. There are currently effective intravenous and endovascular therapies that have the potential to improve functional outcome when used in the appropriate patient population. The utilization of various imaging modalities has been shown to be crucial in identifying which patients may benefit from these therapies. Therefore, a thorough understanding of the role that imaging plays in guiding therapeutic decisions in acute ischemic stroke patients is important. PMID- 26362876 TI - Drug-involved Mexican-origin girls' HIV prevention needs: A pilot study. AB - The purpose of this pilot study was to collect data to inform the development of an HIV prevention program for drug-involved Mexican-origin (MO) adolescent girls. Eighteen in-depth semi-structured interviews were conducted with drug-involved MO girls in addition to focus group discussions with nineteen other drug-involved MO girls and eight clinical service providers in 2009-2010. Emergent themes indicated that HIV prevention programs for drug-involved MO girls should be girl centered, focused on relationship development, and include trained peer facilitators who share the same cultural and "street" background as the girls. The program should omit scare tactics associated with risky sexual behaviors and emphasize individual empowerment skills useful to negotiate sexual decisions successfully. In addition, a girl-centered intervention for MO girls should address important concerns for this group, including resistance skills and strategies regarding relationships with older men, teenage motherhood, sexual infidelity, sexual coercion, and dating violence. Intervention activities should also be interactive with an emphasis on guiding girls as they learn to critically assess personal risk while at the same time learning skills and resources to address these issues in real life. PMID- 26362877 TI - Spatial assessment of monitoring network in coastal waters: a case study of Kuwait Bay. AB - Spatial analyses of water-quality-monitoring networks in coastal waters are important because pollution sources vary temporally and spatially. This study was conducted to evaluate the spatial distribution of the water-quality-monitoring network of Kuwait Bay using both geostatistical and multivariate techniques. Three years of monthly data collected from six existing monitoring stations covering Kuwait Bay between 2009 and 2011 were employed in conjunction with data collected from 20 field sampling sites. Field sampling locations were selected based on a stratified random sampling scheme oriented by an existing classification map of Kuwait Bay. Two water quality datasets obtained from different networks were compared by cluster analysis applied to the Water Quality Index (WQI) and other water quality parameters, after which the Kriging method was used to generate distribution maps of water quality for spatial assessment. Cluster analysis showed that the current monitoring network does not represent water quality patterns in Kuwait Bay. Specifically, the distribution maps revealed that the existing monitoring network is inadequate for heavily polluted areas such as Sulaibikhat Bay and the northern portion of Kuwait Bay. Accordingly, the monitoring system in Kuwait Bay must be revised or redesigned. The geostatistical approach and cluster analysis employed in this study will be useful for evaluating future proposed modifications to the monitoring stations network in Kuwait Bay. PMID- 26362878 TI - Effects of simulated acid rain on the morphology, phenology and dry biomass of a local variety of maize (Suwan-1) in Southwestern Nigeria. AB - Effects of acid rain on the morphology, phenology and dry biomass of maize (Suwan 1 variety) were investigated. The maize seedlings were subjected to different pH treatments (1.0, 2.0, 3.0, 4.0, 5.0 and 6.0) of simulated acid rain (SAR) with pH 7.0 as the control for a period of 90 days. The common morphological defects due to SAR application were necrosis and chlorosis. It was observed that necrosis increased in severity as the acidity increased whilst chlorosis was dominant as the acidity decreased. SAR encouraged rapid floral and cob growth but with the consequence of poor floral and cob development in pH 1.0 to 3.0 treatments. The result for the dry biomass indicates that pH treatments 2.0 to 7.0 for total plant biomass were not significantly different (P > 0.05) from one another, but were all significantly higher (P < 0.05) than pH 1.0. Therefore, it may be deduced that Suwan-1 has the potential to withstand acid rain but with pronounced morphological and phenological defects which, however, have the capacity to reduce drastically the market value of the crop. Therefore, it may be concluded that Suwan-1 tolerated acid rain in terms of the parameters studied at pH 4.0 to 7.0 which makes it a suitable crop in acid rain-stricken climes. This research could also serve as a good reference for further SAR studies on maize or other important cereals. PMID- 26362879 TI - Nephrolithiasis for the primary care physician. PMID- 26362880 TI - A Systematic Review of the Factors that Patients Use to Choose their Surgeon. AB - BACKGROUND: Given surgery's inherent risks, a patient should be able to make the most informed decisions possible in selecting surgical treatment. However, there is little information on what factors patients deem important when choosing a surgeon. We performed a systematic review of the literature focused on how patients select surgical care, focusing on identification of factors that influence patient choice as well as important sources of information used by patients. METHODS: A search of all available literature on factors associated with choice of surgeon/surgical care, as well as sources of information used by patients before undergoing surgery, was conducted using the MEDLINE/PubMed electronic database. RESULTS: Of the 2315 publications identified, 86 studies met inclusion criteria. Overall, patients draw upon a wide range of factors when choosing surgical care. Surgeon reputation and competency stood out as the most valued professional attributes. Patients also often selected surgeons based on their interpersonal skills. Many patients chose surgical care using hospital, rather than surgeon, characteristics. For these patients, hospital reputation and hospital distance were factors of primary importance. Importantly, most patients relied on word-of-mouth and physician referrals when choosing a surgeon. Patients also expressed interest in quality information on surgeons, indicating that these data would be useful in decision-making. CONCLUSIONS: Patients draw upon a myriad of factors when choosing a surgeon and the circumstances surrounding patients' decisions maybe differ based on sociodemographic, cultural, as well as other factors. Additional information on how patients choose surgeons or hospitals will help providers assist patients in finding their preferred caregivers. PMID- 26362881 TI - The value of noncoronary atherosclerosis for identifying coronary artery disease: results of the Leipzig LIFE Heart Study. AB - BACKGROUND: Despite the widespread use of noninvasive testing prior to invasive coronary diagnostic the diagnostic yield of elective coronary angiography has been reported low in subjects with suspected obstructive CAD. OBJECTIVE: To determine the predictive value of noncoronary atherosclerosis (NCA) in subjects with suspected stable coronary artery disease (CAD) intended to invasive coronary angiography. METHODS: Ultrasound-based assessment of carotid artery plaque (CAP), carotid intima-media thickness (CIMT) and ankle-brachial index (ABI) was performed in 2216 subjects with suspected CAD prior to coronary angiography. Logistic regression and c-statistics were used to analyze the diagnostic value of NCA for the presence of obstructive CAD and the intention to revascularization. RESULTS: Percentage of positive results of elective coronary angiography was low but comparable to other studies (41% obstructive CAD). We identified 1323 subjects (60%) with NCA, most of them were characterized by CAP (93%). CAP independently predicted obstructive CAD in addition to traditional risk factors and clinical factors while CIMT and ABI failed to improve the prediction. The presence of NCA and typical angina were the strongest predictors for obstructive CAD (OR 4.0 and 2.4, respectively). A large subgroup of patients (n = 703, 32%) with atypical clinical presentation and lack of NCA revealed a low indication for revascularization <15% indicating a large proportion of subjects with non obstructive CAD in this subgroup. CONCLUSION: The evaluation of noncoronary atherosclerosis has the potential to impact clinical decision making and to direct subsequent diagnostic procedures in subjects with suspected coronary artery disease. CLINICAL TRIAL REGISTRATION: NCT00497887. PMID- 26362882 TI - ECG changes on continuous telemetry preceding in-hospital cardiac arrests. AB - BACKGROUND: About 200,000 patients suffer from in-hospital cardiac arrest (IHCA) annually. Identification of at-risk patients is key to improving outcomes. The use of continuous ECG monitoring in identifying patients at risk for developing IHCA has not been studied. OBJECTIVE: To describe the profile and timing of ECG changes prior to IHCA. DESIGN: Retrospective, observational. SETTING: Single 520 bed tertiary care hospital. PATIENTS: IHCA in adults between April 2010 and March 2012 with at least 3 hours of continuous telemetry data immediately prior to IHCA. MEASUREMENTS: We evaluated up to 24 hours of telemetry data preceding IHCA for changes in PR, QRS, ST segment, arrhythmias, and QTc in ventricular tachycardia cases. We determined mechanism and likely clinical cause of the arrest by chart and telemetry review. RESULTS: We studied 81 IHCA patients, in whom the mechanism was ventricular tachycardia/fibrillation in 14 (18%), bradyasystolic in 21 (26%), and pulseless electrical activity (PEA) in 46 (56%). Preceding ECG changes were ST segment changes (31% of cases), atrial tachyarrhythmias (21%), bradyarrhythmias (28%), P wave axis change (21%),QRS prolongation (19%), PR prolongation (17%), isorhythmic dissociation (14%), nonsustained ventricular tachycardia (6%), and PR shortening (5%). At least one of these was present in 77% of all cases, and in 89% of IHCA caused by respiratory or multiorgan failure. Bradyarrhythmias were primarily seen with IHCA in the setting of respiratory or multiorgan failure, and PR and QRS prolongation with IHCA and concomitant multiorgan failure. LIMITATIONS: This is a retrospective study with a limited number of cases; each patient serves as their own control, and a separate control population has not yet been studied. CONCLUSIONS: ECG changes are commonly seen preceding IHCA, and have a pathophysiologic basis. Automated detection methods for ECG changes could potentially be used to better identify patients at risk for IHCA. PMID- 26362883 TI - Another case of transient resolution of chronic complete right bundle branch block following an acute myocardial infarction. PMID- 26362884 TI - REM sleep modulation by perifornical orexinergic inputs to the pedunculo-pontine tegmental neurons in rats. AB - Rapid eye movement sleep (REMS) is regulated by the interaction of the REM-ON and REM-OFF neurons located in the pedunculo-pontine-tegmentum (PPT) and the locus coeruleus (LC), respectively. Many other brain areas, particularly those controlling non-REMS (NREMS) and waking, modulate REMS by modulating these REMS related neurons. Perifornical (PeF) orexin (Ox)-ergic neurons are reported to increase waking and reduce NREMS as well as REMS; dysfunction of the PeF neurons are related to REMS loss-associated disorders. Hence, we were interested in understanding the neural mechanism of PeF-induced REMS modulation. As a first step we have recently reported that PeF Ox-ergic neurons modulate REMS by influencing the LC neurons (site for REM-OFF neurons). Thereafter, in this in vivo study we have explored the role of PeF inputs on the PPT neurons (site for REM-ON neurons) for the regulation of REMS. Chronic male rats were surgically prepared with implanted bilateral cannulae in PeF and PPT and electrodes for recording sleep-waking patterns. After post-surgical recovery sleep-waking-REMS were recorded when bilateral PeF neurons were stimulated by glutamate and simultaneously bilateral PPT neurons were infused with either saline or orexin receptor1 (OX1R) antagonist. It was observed that PeF stimulation increased waking and decreased NREMS as well as REMS, which were prevented by OX1R antagonist into the PPT. We conclude that the PeF stimulation-induced reduction in REMS was likely to be due to inhibition of REM-ON neurons in the PPT. As waking and NREMS are inversely related, subject to confirmation, the reduction in NREMS could be due to increased waking or vice versa. Based on our findings from this and earlier studies we have proposed a model showing connections between PeF and PPT-neurons for REMS regulation. PMID- 26362885 TI - mTOR signaling controls VGLUT2 expression to maintain pain hypersensitivity after tissue injury. AB - Mammalian target of rapamycin (mTOR) is a serine-threonine protein kinase that controls protein synthesis in the nervous system. Here, we characterized the role of protein synthesis regulation due to mTOR signaling in rat dorsal root ganglion (DRG) following plantar incision. The number of phosphorylated mTOR (p-mTOR) positive neurons was increased 2-4days after the incision. Rapamycin inhibited p mTOR expression in the DRG and thermal hypersensitivity 3days but not 1day after the incision. Vesicular glutamate transporter 2 (VGLUT2) expression was increased after the plantar incision, which was inhibited by rapamycin. These results demonstrated that tissue injury induces phosphorylation of mTOR and increased protein level of VGLUT2 in the DRG neurons. mTOR phosphorylation involves in maintenance of injury-induced thermal hypersensitivity. PMID- 26362886 TI - Critical role of the neural pathway from the intermediate medial mesopallium to the intermediate hyperpallium apicale in filial imprinting of domestic chicks (Gallus gallus domesticus). AB - Filial imprinting in precocial birds is a useful model for studying early learning and cognitive development, as it is characterized by a well-defined sensitive or critical period. We recently showed that the thyroid hormone 3,5,3' triiodothyronine (T3) determines the onset of the sensitive period. Moreover, exogenous injection of T3 into the intermediate medial mesopallium (IMM) region (analogous to the associative cortex in mammals) enables imprinting even on post hatch day 4 or 6 when the sensitive period has been terminated. However, the neural mechanisms downstream from T3 action in the IMM region remain elusive. Here, we analyzed the functional involvement of the intermediate hyperpallium apicale (IMHA) in T3 action. Bilateral excitotoxic ablation of the IMHA prevented imprinting in newly hatched chicks, and also suppressed the recovery of the sensitive period by systemic intra-venous or localized intra-IMM injection of T3 in day-4 chicks. In contrast to the effect in the IMM, direct injection of T3 into the IMHA did not enable imprinting in day-4 chicks. Moreover, bilateral ablation of IMHA after imprinting training impaired recall. These results suggest that the IMHA is critical for memory acquisition downstream following T3 action in the IMM and further, that it receives and retains information stored in the IMM for recall. Furthermore, both an avian adeno-associated viral construct containing an anterograde tracer (wheat-germ agglutinin) and a retrograde tracer (cholera toxin subunit B) revealed neural connections from the IMM to the IMHA. Taken together, our findings suggest that hierarchical processes from the primary area (IMM) to the secondary area (IMHA) are required for imprinting. PMID- 26362887 TI - Brain abnormalities in high-risk violent offenders and their association with psychopathic traits and criminal recidivism. AB - Measures of psychopathy have been proved to be valuable for risk assessment in violent criminals. However, the neuronal basis of psychopathy and its contribution to the prediction of criminal recidivism is still poorly understood. We compared structural imaging data from 40 male high-risk violent offenders and 37 non-delinquent healthy controls via voxel-based morphometry. Psychopathic traits and risk of violence recidivism were correlated with gray matter volume (GMV) of regions of interest previously shown relevant for criminal behavior. Relative to controls, criminals showed less GMV in the prefrontal cortex (PFC) and more GMV in cerebellar regions and basal ganglia structures. Within criminals, we found a negative correlation between prefrontal GMV and psychopathy. Additionally, there was a positive correlation between cerebellar GMV and psychopathy as well as risk of recidivism for violence. Moreover, GMVs of the basal ganglia and supplementary motor area (SMA) were positively correlated with anti-sociality. GMV of the amygdala was negatively correlated with dynamic risk for violence recidivism. In contrast, GMV of (para)limbic areas (orbitofrontal cortex, insula) was positively correlated with anti-sociality and risk of violence recidivism. The current investigation revealed that in violent offenders deviations in GMV of the PFC as well as areas involved in the motor component of impulse control (cerebellum, basal ganglia, SMA) are differentially related to psychopathic traits and the risk of violence recidivism. The results might be valuable for improving existing risk assessment tools. PMID- 26362888 TI - Genetic analysis of the isolated Faroe Islands reveals SORCS3 as a potential multiple sclerosis risk gene. AB - BACKGROUND: In search of the missing heritability in multiple sclerosis (MS), additional approaches adding to the genetic discoveries of large genome-wide association studies are warranted. OBJECTIVE: The objective of this research paper is to search for rare genetic MS risk variants in the genetically homogenous population of the isolated Faroe Islands. METHODS: Twenty-nine Faroese MS cases and 28 controls were genotyped with the HumanOmniExpressExome-chip. The individuals make up 1596 pair-combinations in which we searched for identical-by descent shared segments using the PLINK-program. RESULTS: A segment spanning 63 SNPs with excess case-case-pair sharing was identified (0.00173 < p > 0.00212). A haplotype consisting of 42 of the 63 identified SNPs which spanned the entire the Sortilin-related vacuolar protein sorting 10 domain containing receptor 3 (SORCS3) gene had a carrier frequency of 0.34 in cases but was not present in any controls (p = 0.0008). CONCLUSION: This study revealed an oversharing in case case-pairs of a segment spanning 63 SNPs and the entire SORCS3. While not previously associated with MS, SORCS3 appears to be important in neuronal plasticity through its binding of neurotrophin factors and involvement in glutamate homeostasis. Although additional work is needed to scrutinise the genetic effect of the SORCS3-covering haplotype, this study suggests that SORCS3 may also be important in MS pathogenesis. PMID- 26362890 TI - Uniform guidelines for reporting COI within industry-sponsored clinical trials (ISCT). PMID- 26362889 TI - A case of relapsing-remitting tumour-like inflammation of the central nervous system. AB - The case of a 37-year-old woman suffering from a relapsing-remitting tumefactive inflammatory disease of the central nervous system (CNS) is described. The patient had four severe relapses over eight years, and was treated with steroids, immunosuppression and plasma-exchange with modest benefit. No magnetic resonance imaging or cerebrospinal spinal fluid findings suggestive of multiple sclerosis emerged during the eight-year follow-up. 'Relapsing-remitting tumefactive inflammation' seems to have the features of a distinct inflammatory CNS disease. PMID- 26362891 TI - Altered resting-state functional connectivity in cognitively preserved pediatric onset MS patients and relationship to structural damage and cognitive performance. AB - OBJECTIVE: To evaluate resting-state functional connectivity (FC) and relationship to brain volumes and cognition in a sample of cognitively preserved pediatric-onset multiple sclerosis (MS) patients. METHODS: Sixteen cognitively intact pediatric-onset MS patients and 15 healthy age- and sex-matched controls underwent cognitive testing and 3T anatomical and functional MRI. Resting-state FC patterns were examined using region-of-interest-based timeseries correlations. RESULTS: Compared to controls, pediatric-onset MS patients demonstrated higher FC of the precuneus, particularly with the anterior cingulate cortex (z=4.21, p<.001), frontal medial cortex (z=3.48, p<.001), and cerebellum (z=3.72, p<.001). Greater T2 lesion volume and lower normalized thalamic volume were associated with reduced FC of the thalamus, especially for FC with the right superior occipital region (t=-2.87, p=.0123 and t=2.27, p=.04 respectively). FC of the left frontal medial cortex was negatively correlated with composite cognitive z score in the pediatric-onset MS group (p<.05). CONCLUSIONS: Greater resting-state FC between posterior and anterior brain regions is present in pediatric-onset MS. With greater disease-related structural pathology, there is a disruption of thalamo-cortical FC. In the absence of actual cognitive impairment, heightened FC of the frontal medial cortex was associated with lower cognitive performance, suggesting that greater functional resources are recruited during resting-state in patients with reduced cognitive efficiency. PMID- 26362892 TI - Pituitary-ovary axis and ovarian reserve in fertile women with multiple sclerosis: A pilot study. AB - Since a decline in the ovary function might impact the reproductive potential in women with multiple sclerosis (MS), we investigated the pituitary-ovary axis and ovarian reserve, including anti-Mullerian hormone (AMH) levels and ultrasound imaging of the ovaries, of 25 relapsing-remitting MS patients and 25 age-matched healthy controls. Mean levels of pituitary-gonadal hormones and age-adjusted parameters of ovarian reserve markers were not significantly different between both groups. Patients with higher disease activity (annualized relapse rate >0.5; n=9) had significantly lower AMH levels, total antral follicle count and ovarian volume, than those with lower disease activity. The finding of poorer ovarian reserve associated with higher disease activity should be taken into consideration since it may negatively impact the reproductive prognosis. PMID- 26362893 TI - Increased albumin quotient (QAlb) in patients after first clinical event suggestive of multiple sclerosis is associated with development of brain atrophy and greater disability 48 months later. AB - BACKGROUND: The utility of blood-brain barrier (BBB) biomarkers for clinical and magnetic resonance imaging progression in multiple sclerosis (MS) has not been extensively investigated. OBJECTIVES: To determine whether cerebrospinal fluid (CSF) measures of BBB at clinical onset predict radiological and clinical deterioration over 48 months. METHODS: This longitudinal study included 182 patients after first clinical event suggestive of MS treated with weekly intramuscular interferon beta-1a. CSF and serum samples were analyzed for leukocytes, total protein, albumin, immunoglobulins, and oligoclonal bands. Optimal thresholds for the albumin quotient (QAlb) were determined. Mixed-effect model analyses, adjusted for age, gender, and treatment escalation, were used to analyze relationship between CSF measures and disease activity outcomes over 48 months of follow-up. RESULTS: Increased QAlb at clinical onset was associated with enlargement of lateral ventricles (p = .001) and greater whole brain (p = .003), white matter (p < .001), corpus callosum (p < .001), and thalamus (p = .003) volume loss over 48 months. Higher QAlb was associated with higher Expanded Disability Status Scale score over 48 months (p = .002). CONCLUSIONS: Increased QAlb at clinical onset is associated with increased brain atrophy and greater disability in patients after first clinical event suggestive of MS. PMID- 26362894 TI - Retinal ganglion cell layer thinning within one month of presentation for optic neuritis. AB - BACKGROUND: Spectral domain optical coherence tomography (SD-OCT) reveals retinal ganglion cell layer plus inner plexiform layer (GCL+IPL) and peripapillary retinal nerve fiber layer (pRNFL) thinning in chronic optic nerve injury. At presentation, swelling of the pRNFL confounds evaluation of early axon loss. OBJECTIVE: We studied whether the GCL+IPL thins before the pRNFL, the trajectory of GCL+IPL loss and relationship to vision. METHODS: We prospectively evaluated 33 eyes (study) with new optic neuritis, using perimetry and SD-OCT with investigative three-dimensional layer segmentation and commercial two-dimensional segmentation to compute the GCL+IPL and pRNFL thickness. RESULTS: At presentation, GCL+IPL thickness (82.4+/-8.8 um) did not differ from unaffected fellow eyes (81.2+/-6.7 um), via the three-dimensional method, while the two dimensional method failed in 9% of study eyes. At 1-2 months, there was thinning of the pRNFL in 10% and of the GCL+IPL in 93% of study eyes. GCL+IPL reduction was greatest during the first 2 months. GCL+IPL thinning at 1-2 months correlated with GCL+IPL thinning at 6 months (r=0.84, P=0.01) and presentation visual acuity (r=0.48, P=0.006) and perimetric mean deviation (r=0.52, P=0.003). CONCLUSION: GGL+IPL is an early biomarker of structural injury in optic neuritis as thinning develops within 1-2 months of onset, prior to pRNFL thinning. PMID- 26362895 TI - Body mass index during adolescence, rather than childhood, is critical in determining MS risk. AB - OBJECTIVE: Obesity in childhood and during adolescence has repeatedly been associated with increased risk of developing multiple sclerosis (MS). We aimed to investigate whether the most critical period occurs during childhood or later, during adolescence. METHODS: Using a population-based case-control study (1586 cases and 2800 controls), individuals with different body sizes at age 10 and different body mass indices at age 20 were compared regarding MS risk, by calculating odds ratios with 95% confidence intervals. Potential interactions between HLA-DRB1*15 and absence of HLA-A*02, respectively, and both childhood and adolescent obesity were evaluated by calculating the attributable proportion due to interaction. RESULTS: Regardless of body size at age 10, individuals with adolescent obesity had a 90% increased risk of MS. Among participants who were not obese at age 20, no association was observed between body size at age 10 and subsequent MS risk. An interaction was observed between the HLA MS risk genes and adolescent, but not childhood, obesity. CONCLUSIONS: Our results suggest that BMI during adolescence, rather than childhood, is critical in determining MS risk. PMID- 26362896 TI - Cognitive impairment at diagnosis predicts 10-year multiple sclerosis progression. AB - BACKGROUND: Cognitive impairment occurs from the early phases of multiple sclerosis (MS), and more frequently affects secondary progressive (SP) subjects than relapsing-remitting (RR). OBJECTIVE: To investigate relationships between cognitive dysfunctions in newly diagnosed RRMS, and long-term MS-related outcomes. METHODS: The present 10-year retrospective longitudinal study included 155 RRMS subjects, tested with the Rao Brief Repeatable Battery at MS diagnosis. The reaching of Expanded Disability Status Scale (EDSS) 4.0, and the SP conversion were recorded. RESULTS: 67 subjects (43.2%) reached EDSS 4.0, and 34 subjects (21.9%) converted to SP during a follow-up period of 10.0+/-1.8 years. Subjects with cognitive impairment at diagnosis had a rate of reaching EDSS 4.0 more than three times greater (p<0.001; HR=3.183), and a rate of SP conversion more than two times greater, as compared to cognitively preserved subjects (p=0.008; HR=2.535). In particular, better scores in the Selective Reminding Test Delayed Recall and in the Symbol Digit Modalities Test at baseline were associated with lower SP conversion rates during the follow-up period (p=0.018; HR=0.835; and p=0.001; HR=0.941, respectively). CONCLUSION: Cognitive impairment, with particular involvement of processing speed and memory, predicts disability progression and SP conversion in newly diagnosed RRMS, highlighting the importance of cognitive assessment from the beginning of MS. PMID- 26362897 TI - Adaptive natural killer cell response to cytomegalovirus and disability progression in multiple sclerosis. AB - BACKGROUND: Human cytomegalovirus (HCMV) causes a highly prevalent infection which may have a multifaceted impact on chronic inflammatory disorders. However, its potential influence in multiple sclerosis (MS) remains controversial. The HCMV-host interaction may induce an adaptive reconfiguration of the natural killer (NK) cell compartment, whose hallmark is a persistent expansion of peripheral NKG2C+ NK-cells. OBJECTIVE: The purpose of this study was to evaluate whether the HCMV-driven NKG2C+ NK-cell expansion is related to the MS clinical course. METHODS: Multicentre analysis of NKG2C expression and genotype according to HCMV serostatus and time of assignment of irreversible disability scores in 246 MS patients prospectively followed up in our institutions. RESULTS: NKG2C expression was unrelated to disease-modifying drugs, remained stable under steady state conditions, and was higher in HCMV(+) NKG2C(+/+) homozygous individuals. NKG2C+ NK-cell expansion in HCMV(+) patients, as compared to HCMV(+) or HCMV(-) patients with lower NKG2C+ NK-cells proportions, conferred a lower risk of progression in Cox regression analysis (Expanded Disability Status Scale (EDSS)>3.0, hazard ratio (HR)=0.33, 95% confidence interval (CI) 0.15-0.71, p=0.005; EDSS>5.5, HR=0.23, 95% CI 0.07-0.74, p=0.014). Neither HCMV serostatus nor NKG2C genotype appeared to be related to disability progression. CONCLUSIONS: HCMV may exert a beneficial influence on MS, decreasing the risk of disability progression in those patients displaying a virus-driven NKG2C+ NK-cell expansion. PMID- 26362899 TI - Tumefactive demyelinating lesions: Characteristics of individual lesions, individual patients, or a unique disease entity? AB - Whether or not recurrent tumefactive demyelinating lesions are a unique form of CNS demyelinating disease or part of the continuum of multiple sclerosis is a question raised by the case report on which this commentary is based. Detailed review and immunopathologic study of biopsy material may not only confirm or refute a diagnosis of demyelinating disease, but potentially uncover unique features that may assist in understanding pathophysiology and nosology of rare cases with recurrent tumefactive demyelination. PMID- 26362898 TI - A 10-year follow-up of the European multicenter trial of interferon beta-1b in secondary-progressive multiple sclerosis. AB - OBJECTIVES: To explore long-term effects of treatment and prognostic relevance of variables assessed at baseline and during the European secondary progressive multiple sclerosis (SPMS) trial of interferon beta 1b (IFNB-1b). METHODS: We assessed 362 patients (60% female; median age 41 years; Expanded Disability Status Scale (EDSS): 5.5; 51% randomized to IFNB-1b) for their EDSS and treatment history after 10 years. Non-parametric analysis of covariance (ANCOVA) and multivariate linear regression models were applied. RESULTS: Median EDSS was 6.0 at the end of the randomized controlled trial (RCT), in the IFNB-1b and placebo groups, and 7.0 in long-term follow-up patients (those receiving IFNB-1b in the RCT were 6.5 and those receiving placebo in the RCT were 7.0; p = 0.086). 24 patients (6.6%) were deceased. The EDSS at baseline and the EDSS change during the RCT were the most important predictors of the EDSS 10 years later (partial R(2): 0.47). The ability to predict changes in EDSS 10 years after the RCT was limited (R(2): 0.12). Magnetic resonance imaging (MRI) measures remained in the predictive models, but explained < 5% of the variability. CONCLUSIONS: The results from this analysis did not provide convincing evidence to support a favorable long-term outcome in those patients allocated IFNB-1b during the RCT, in our SPMS cohort. The progressive stage of the disease remains largely unpredictable by clinical and conventional MRI measures, so better prognostic markers are needed. PMID- 26362900 TI - Efficacy of rituximab in refractory neuromyelitis optica. AB - BACKGROUND: Despite a growing use of rituximab (RTX) in neuromyelitis optica (NMO), data are lacking in patients with refractory NMO (RNMO), defined as cases with at least one relapse during immunosuppressive therapy. OBJECTIVE: The purpose of this study was to assess RTX as a maintenance therapy in RNMO. METHODS: Out of a total of 305 NMO cases from a population-based cohort, 21 RNMO patients received RTX during a mean follow-up period of 31 months. RESULTS: After RTX, 11 patients (52.3%) were relapse free, meaning that 47.7% were refractory to RTX. The mean annualized relapse rate decreased from 1.3 to 0.4 (p<0.001) and median EDSS from 5 to 3 (p=0.02). Body mass index (BMI) was predictive of EDSS worsening. CONCLUSIONS: RTX is an effective and well-tolerated treatment in RNMO. BMI could be a predictive factor for efficacy. PMID- 26362901 TI - Multiple sclerosis lesion formation and early evolution revisited: A weekly high resolution magnetic resonance imaging study. AB - BACKGROUND: Several magnetic resonance imaging (MRI) studies investigated the evolution of multiple sclerosis (MS) lesions to understand the pathophysiological mechanisms leading to blood-brain barrier breakdown and lesion formation. Only a few assessed the early natural history of MS lesions using short-interval longitudinal MRI. OBJECTIVE: The purpose of this study was to characterize MS lesion occurrence and early evolution on high-resolution MRI acquired at weekly intervals. METHODS: Active lesions were characterized on 3D fluid attenuation inversion recovery (FLAIR) and gadolinium-enhanced 3D T1-weighted MRI performed weekly (seven weeks) on five untreated patients with relapsing-remitting MS (RRMS). RESULTS: Active lesions (n=212) were detected in all patients. All showed contrast-enhancement on at least one time-point. Most new lesions (83.5%) were visible on FLAIR and post-contrast T1-weighted images at first detection; 11.2% showed activity on FLAIR images, one or more weeks before the appearance of contrast-enhancement; 12.5% enhanced before being apparent on FLAIR. CONCLUSION: Blood brain barrier disruption is a constant step in the natural history of active MS lesions, but does not always constitute the initial event. These findings are consistent with the existence of a subpopulation of lesions with an 'inside-out' genesis, where neurodegenerative processes might precede microglial activation, and a subsequent adaptive immune response. PMID- 26362902 TI - Progressive MS: from pathophysiology to drug discovery. AB - Progressive multiple sclerosis (MS) will be a major area of research interest for years to come. No treatments exist and success in the field will generalise to other neurological conditions where neurodegeneration coexists with neuroinflammation. The issue is complex, and interdisciplinary approaches - uniting scientists with different competences (neurobiology, immunogenetics, etc.) and 'mindsets' (academia and industry) - will be decisive. The International Progressive MS Alliance is catalysing this process through various initiatives, the most recent of which was a meeting where scientists from academia (also outside the MS field) and from industry reviewed data and strategies to determine the next steps towards the translation of current knowledge into effective therapies.Key findings are:(i). Concerted efforts are essential to prioritise pathogenetic mechanisms according to impact on the disease and druggability.(ii). Combination therapies will probably be needed, possibly early in the disease, along with new trial designs and treatment schedules.(iii). Drug screenings are a pragmatic approach hopefully enriched by the use of neural and oligodendrocyte progenitors differentiated from induced pluripotent stem cells (iPSCs).(iv). The field of network biology will increase our ability to predict therapeutic targets.(v). Genome-wide association studies (GWAS) must try to identify variants associated with disease progression. PMID- 26362903 TI - Effect of fingolimod on cardiac autonomic regulation in patients with multiple sclerosis. AB - BACKGROUND: Fingolimod modulates sphingosine-1-phosphate receptors that are also found in cardiovascular tissue. OBJECTIVE: To investigate the effects of fingolimod on cardiac autonomic regulation prospectively. METHODS: Twenty-seven relapsing-remitting multiple sclerosis patients underwent 24-hour electrocardiogram recording before, at the first day of fingolimod treatment (1d) and after three months of continuous dosing (3mo). The time interval between two consecutive R-peaks (RR-interval) was measured. Cardiac autonomic regulation was assessed by the various parameters of heart rate variability. Parasympathetic stimulation prolongs the RR-interval and increases heart rate variability while the effects of sympathetic stimulation are mainly the opposite. The low frequency/high frequency ratio reflects sympathovagal balance. RESULTS: From baseline to 1d, a prolongation of the RR-interval (P<0.001), an increase in the values of various heart rate variability parameters (P<0.05 to P<0.001) and a decrease in the low frequency/high frequency ratio (P<0.05) were demonstrated. At 3mo, although the RR-interval remained longer (P<0.01), the values of various heart rate variability parameters were lower (P<0.01 to P<0.001) as compared to baseline. At 3mo, the low frequency/high frequency ratio (P<0.05) was higher in men than in women although no such difference was found at baseline or at 1d. CONCLUSIONS: After an initial increase in parasympathetic regulation, continuous fingolimod dosing shifts cardiac autonomic regulation towards sympathetic predominance, especially in men. Careful follow-up of fingolimod-treated relapsing-remitting multiple sclerosis patients is warranted as sympathetic predominance associates generally with impaired outcome.ClinicalTrials.cov: NCT01704183. PMID- 26362904 TI - Higher intake of omega-3 polyunsaturated fatty acids is associated with a decreased risk of a first clinical diagnosis of central nervous system demyelination: Results from the Ausimmune Study. AB - BACKGROUND: There is contradictory evidence for a role of dietary fat in risk of multiple sclerosis (MS). OBJECTIVES: To examine the association between usual fat intake (total, saturated, monounsaturated (MUFA), polyunsaturated (PUFA), omega-3 and omega-6) and risk of a first clinical diagnosis of CNS demyelination (FCD). METHODS: Multi-centre incident case-control study in four regions of Australia during 2003-2006. Cases were aged 18-59 years and had a FCD; controls were matched to a case on age, sex and location. Dietary data were collected using a validated food frequency questionnaire. RESULTS: In 267 cases and 517 controls with dietary data, higher intake (per g/day) of omega-3 PUFA (adjusted odds ratio, AOR=0.61 (95% CI 0.40-0.93)), and particularly that derived from fish (AOR=0.54 (95% CI 0.31-0.93)) rather than from plants (AOR=0.75 (95% CI 0.39 1.43)) was associated with a decreased risk of FCD. Total fat intake and intake of other types of fat were not associated with FCD risk. CONCLUSIONS: There was a significant decrease in FCD risk with higher intake of omega-3 PUFA, particularly that originating from fish. There was no evidence to indicate that the intake of other types of dietary fat or fat quantity in the previous 12 months was associated with an altered risk of FCD. PMID- 26362905 TI - Optical coherence tomography indicates disease activity prior to clinical onset of central nervous system demyelination. AB - BACKGROUND: Establishing biomarkers for predicting disease activity in demyelinating disease of the central nervous system is crucial for designing appropriate disease modifiying treatment strategies. OBJECTIVE: To investigate retinal findings and disease activity in patients with radiologically isolated and clinically isolated syndromes. METHODS: We performed retinal optical coherence tomography and cerebral magnetic resonance imaging in healthy control individuals (n=19), in individuals with non-specific white matter lesions (n=18), and in patients with clinically isolated syndromes (n=18) and radiologically isolated syndromes (n=20). RESULTS: Reduced volume of retinal nerve fibre layer and increased volume of inner nuclear layer at baseline correlated with subsequent disease activity as measured by an increase in cerebral T2 lesion load in patients with radiologically isolated syndromes. Reduced volume of retinal nerve fibre layer and increased volumes of inner and outer nuclear layer were associated with progression into multiple sclerosis in patients with clinically isolated syndromes. CONCLUSION: Patients with radiologically and clinically isolated syndromes behave similarly concerning paraclinical disease activity in cerebral magnetic resonance imaging. In both conditions, reduction of retinal nerve fibre layer and increased inner nuclear layer and outer nuclear layer volumes predict disease activity and are associated with progression into multiple sclerosis. PMID- 26362906 TI - Assessment of nociceptive system in vegetative and minimally conscious state by using laser evoked potentials. AB - PRIMARY OBJECTIVE: The aim of this study is to assess if laser evoked potentials (LEPs) examination should be considered as an objective evidence of potential or residual pain perception capacity in vegetative (VS) and minimally conscious state (MCS) patients and if it could be a feasible methodology in order to differentiate these two clinical entities. RESEARCH DESIGN: This is a cross sectional observational study focusing on the role of LEP examination, which is an easy and objective neurophysiological approach of the nociceptive system. METHODS AND PROCEDURES: Thirteen VS and 10 MCS patients were enrolled. All subjects were evaluated clinically by using validated behavioural scales and underwent to upper and lower limbs LEP recording. MAIN OUTCOMES AND RESULTS: Intra-group LEPs analysis in VS patients highlighted significant differences for N2P2 latency (p = 0.036) and amplitude (p = 0.018). Inter-group LEPs analysis showed significant differences in post-anoxic condition for N2P2 latency (p = 0.034), amplitude (p = 0.034) and a trend in N2P2 latency in brain trauma (p = 0.07). Interestingly, correlation analysis showed a significant relationship between N2P2 amplitude and Coma Recovery Scale-Revised scoring in the post traumatic VS (r = 0.823, p = 0.044). CONCLUSIONS: The findings lead to detection of potential markers of conscious pain perception in patients with DOC, with important impact on therapeutic and rehabilitative management, and provide new information that may allow a better differential diagnosis. PMID- 26362907 TI - Fingolimod versus interferon beta/glatiramer acetate after natalizumab suspension in multiple sclerosis. AB - The comparative effectiveness of fingolimod versus interferon beta/glatiramer acetate was assessed in a multicentre, observational, prospectively acquired cohort study including 613 patients with relapsing multiple sclerosis discontinuing natalizumab in the Italian iMedWeb registry. First, after natalizumab suspension, the relapse risk during the untreated wash-out period and during the course of switch therapies was estimated through Poisson regression analyses in separated models. During the wash-out period an increased risk of relapses was found in patients with a higher number of relapses before natalizumab treatment (incidence rate ratio = 1.31, P = 0.0014) and in patients discontinuing natalizumab due to lack of efficacy (incidence rate ratio = 2.33, P = 0.0288), patient's choice (incidence rate ratio = 2.18, P = 0.0064) and adverse events (incidence rate ratio = 2.09, P = 0.0084). The strongest independent factors influencing the relapse risk after the start of switch therapies were a wash-out duration longer than 3 months (incidence rate ratio = 1.78, P < 0.0001), the number of relapses experienced during and before natalizumab treatment (incidence rate ratio = 1.61, P < 0.0001; incidence rate ratio = 1.13, P = 0.0118, respectively) and the presence of comorbidities (incidence rate ratio = 1.4, P = 0.0097). Switching to fingolimod was associated with a 64% reduction of the adjusted-risk for relapse in comparison with switching to interferon beta/glatiramer acetate (incidence rate ratio = 0.36, P < 0.0001). Secondly, patients who switched to fingolimod or to interferon beta/glatiramer acetate were propensity score-matched on a 1-to-1 basis at the switching date. In the propensity score-matched sample a Poisson model showed a significant lower incidence of relapses in patients treated with fingolimod in comparison with those treated with interferon beta/glatiramer acetate (incidence rate ratio = 0.52, P = 0.0003) during a 12-month follow-up. The cumulative probability of a first relapse after the treatment switch was significantly lower in patients receiving fingolimod than in those receiving interferon beta/glatiramer acetate (P = 0.028). The robustness of this result was also confirmed by sensitivity analyses in subgroups with different wash-out durations (less or more than 3 months). Time to 3-month confirmed disability progression was not significantly different between the two groups (Hazard ratio = 0.58; P = 0.1931). Our results indicate a superiority of fingolimod in comparison to interferon beta/glatiramer acetate in controlling disease reactivation after natalizumab discontinuation in the real life setting. PMID- 26362908 TI - No parkinsonism in SCA2 and SCA3 despite severe neurodegeneration of the dopaminergic substantia nigra. AB - See Klockgether (doi:10.1093/awv253) for a scientific commentary on this article.The spinocerebellar ataxias types 2 (SCA2) and 3 (SCA3) are autosomal dominantly inherited cerebellar ataxias which are caused by CAG trinucleotide repeat expansions in the coding regions of the disease-specific genes. Although previous post-mortem studies repeatedly revealed a consistent neurodegeneration of the dopaminergic substantia nigra in patients with SCA2 and with SCA3, parkinsonian motor features evolve only rarely. As the pathophysiological mechanism how SCA2 and SCA3 patients do not exhibit parkinsonism is still enigmatic, we performed a positron emission tomography and a post-mortem study of two independent cohorts of SCA2 and SCA3 patients with and without parkinsonian features. Positron emission tomography revealed a significant reduction of dopamine transporter levels in the striatum as well as largely unaffected postsynaptic striatal D2 receptors. In spite of this remarkable pathology in the motor mesostriatal pathway, only 4 of 19 SCA2 and SCA3 patients suffered from parkinsonism. The post-mortem investigation revealed, in addition to an extensive neuronal loss in the dopaminergic substantia nigra of all patients with spinocerebellar ataxia, a consistent affection of the thalamic ventral anterior and ventral lateral nuclei, the pallidum and the cholinergic pedunculopontine nucleus. With the exception of a single patient with SCA3 who suffered from parkinsonian motor features during his lifetime, the subthalamic nucleus underwent severe neuronal loss, which was clearly more severe in its motor territory than in its limbic or associative territories. Our observation that lesions of the motor territory of the subthalamic nucleus were consistently associated with the prevention of parkinsonism in our SCA2 and SCA3 patients matches the clinical experience that selective targeting of the motor territory of the subthalamic nucleus by focal lesions or deep brain stimulation can ameliorate parkinsonian motor features and is likely to counteract the manifestation of parkinsonism in SCA2 and SCA3 despite a severe neurodegeneration of the dopaminergic substantia nigra. PMID- 26362909 TI - Screening for CHCHD10 mutations in a large cohort of sporadic ALS patients: no evidence for pathogenicity of the p.P34S variant. PMID- 26362911 TI - Pretreatment hematologic markers as prognostic factors in patients with nasopharyngeal carcinoma: Neutrophil-lymphocyte ratio and platelet-lymphocyte ratio. AB - BACKGROUND: Pretreatment hematological markers of inflammatory response have emerged as prognostic factors for patients with cancer. In this study, we evaluated the prognostic significance of various hematologic parameters in patients with nasopharyngeal carcinoma (NPC). METHODS: Clinical data from 251 patients with NPC were retrospectively collected. Neutrophil counts, lymphocyte counts, platelet counts, neutrophil-lymphocyte ratio (NLR), and platelet lymphocyte ratio (PLR) were adopted as potential prognostic biomarkers. The Kaplan-Meier method and log-rank test were adopted to calculate and compare the progression-free survival (PFS) and overall survival (OS) rates. The Cox proportional hazards model was used to carry out univariate and multivariate analyses. RESULTS: NLR >=2.7 (hazard ratio [HR] = 2.01; 95% confidence interval [CI] = 1.23-3.29; p = .005) and PLR >=167.2 (HR = 2.12; 95% CI = 1.35-3.33; p = .001) were significantly associated with shorter PFS, whereas PLR >=163.4 (HR = 2.64; 95% CI = 1.25-5.60; p = .011) was correlated with poor OS. CONCLUSION: Pretreatment NLR and PLR can be independent prognostic factors for patients with NPC. (c) 2015 Wiley Periodicals, Head Neck 38: E1332-E1340, 2016. PMID- 26362910 TI - CHCHD10 Pro34Ser is not a highly penetrant pathogenic variant for amyotrophic lateral sclerosis and frontotemporal dementia. PMID- 26362912 TI - Rapid and sensitive screening of some acidic micronutrients in infant foods by HPLC with fluorescent detector. AB - BACKGROUND: Currently, commercially prepared complementary foods have become an important part of the diet of many infants and toddlers. But the method for simultaneous analysis of different types of micronutrient remains poorly investigated, which hinders the rapid and comprehensive quality control of infant foods. In the presented study, we first tried to employ the fluorescence labeling strategy combined with high-performance liquid chromatography-fluorescence detection for simultaneous determination of some acidic micronutrients including biotin, nicotinic acid, linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, arachidonic acid and linoleic acid in infant foods. RESULTS: 2-(5 Benzoacridine) ethyl-p-toluenesulfonate was used as the fluorescence labeling reagent for simultaneous labeling of the seven components. The labeling conditions were optimized systematically by response surface methodology. The correlation coefficients for the calibration curves of the tested compounds ranged from 0.9991 to 0.9998. Limits of detection were in the range of 1.99-3.05 nmol L(-1) . Relative standard deviation values of retention time and peak area of seven compounds were less than 0.05% and 0.75%, respectively. The intra- and inter-day precision was in the range of 1.81-3.80% and 3.21-4.30%, respectively. When applied to analysis of several infant foods it showed good applicability. CONCLUSION: The developed method has been proven to be simple, inexpensive, selective, sensitive, accurate and reliable for analysis of some acidic micronutrients in infant foodstuffs. Furthermore, this developed method also has powerful potential in the analysis of many other complementary foodstuffs. (c) 2015 Society of Chemical Industry. PMID- 26362913 TI - Chondrogenic potential of physically treated bovine cartilage matrix derived porous scaffolds on human dermal fibroblast cells. AB - Extracellular matrices have drawn attention in tissue engineering as potential biomaterials for scaffold fabrication because of their bioactive components. Noninvasive techniques of scaffold fabrication and cross-linking treatments are believed to maintain the integrity of bioactive molecules while providing proper architectural and mechanical properties. Cartilage matrix derived scaffolds are designed to support the maintenance of chondrocytes and provide proper signals for differentiation of chondroinducible cells. Chondroinductive potential of bovine articular cartilage matrix derived porous scaffolds on human dermal fibroblasts and the effect of scaffold shrinkage on chondrogenesis were investigated. An increase in sulfated glycosaminoglycans production along with upregulation of chondrogenic genes confirmed that physically treated cartilage matrix derived scaffolds have chondrogenic potential on human dermal fibroblasts. PMID- 26362914 TI - Effect of intra-operative autonomic nerve stimulation on pelvic nerve preservation during radical laparoscopic proctectomy. AB - AIM: This study assessed the effect of intra-operative electrical nerve stimulation (INS) on pelvic autonomic nerve preservation (PANP) during laparoscopic resection for rectal cancer. METHOD: A total of 189 consecutive cases of radical laparoscopic proctectomy were included. PANP was assessed visually or with INS. Urinary function was evaluated by residual urine volume (RUV), International Prostatic Symptom Score (IPSS) and recatheterization rate. Erectile function was evaluated using the International Index of Erectile Function (IIEF-5) scale. RESULTS: INS successfully confirmed PANP in 65 (91.5%) patients, while direct vision confirmed PANP in only 72 (61.0%) patients. Compared with the successfully confirmed patients, failed patients in the INS group exhibited higher postoperative RUV (100.0 +/- 34.6 vs 25.2 +/- 13.6 ml, P = 0.003), higher IPSS (7 days, 20.0 +/- 8.6 vs 6.5 +/- 2.4, P = 0.012; 1 month, 13.5 +/- 6.0 vs 5.3 +/- 1.9, P = 0.020; 6 months, 11.7 +/- 5.1 vs 4.5 +/- 1.7, P = 0.018), a greater number of incidences of a micturition disorder (66.7% vs 1.5%, P = 0.000), higher recatheterization rates (33.3% vs 1.5%, P = 0.017) and a lower IIEF score at 3 months (8.25 +/- 0.96 vs 10.93 +/- 1.99, P = 0.012) and 6 months (12.50 +/- 1.29 vs 15.63 +/- 1.65, P = 0.001) postoperatively. Compared with the vision group, the INS group had less deterioration in postoperative RUV (31.5 +/- 26.4 vs 54.0 +/- 46.7 ml, P = 0.000), lower IPSS (7 days, 7.7 +/- 5.0 vs 11.0 +/- 6.6, P = 0.000; 1 month, 6.0 +/- 3.3 vs 7.6 +/- 5.4, P = 0.012) and higher IIEF score (3 months, 10.69 +/- 2.07 vs 9.42 +/- 2.05, P = 0.001; 6 months, 15.36 +/- 1.85 vs 13.64 +/- 2.00, P = 0.000) as well as a lower incidence of urination disorders (7.0% vs 17.8%, P = 0.038). CONCLUSION: INS is effective for the accurate evaluation of PANP during radical laparoscopic proctectomy. Combined with INS, laparoscopic proctectomy is more effective in urogenital function protection. PMID- 26362915 TI - Clomiphene-Associated Suicide Behavior in a Man Treated for Hypogonadism: Case Report and Review of The Literature. PMID- 26362916 TI - The Early-Career Consultation Psychiatrist: The Superspecialist. PMID- 26362917 TI - Exercise-induced elevation of liver enzymes in a healthy female research volunteer. PMID- 26362918 TI - Polyallergy as a Proxy: Premature Yet Promising. PMID- 26362919 TI - Neuropsychiatric Lupus is Complex. PMID- 26362920 TI - Mechanical stimulation in the engineering of heart muscle. AB - Recreating the beating heart in the laboratory continues to be a formidable bioengineering challenge. The fundamental feature of the heart is its pumping action, requiring considerable mechanical forces to compress a blood filled chamber with a defined in- and outlet. Ventricular output crucially depends on venous loading of the ventricles (preload) and on the force generated by the preloaded ventricles to overcome arterial blood pressure (afterload). The rate of contraction is controlled by the spontaneously active sinus node and transmission of its electrical impulses into the ventricles. The underlying principles for these physiological processes are described by the Frank-Starling mechanism and Bowditch phenomenon. It is essential to consider these principles in the design and evaluation of tissue engineered myocardium. This review focuses on current strategies to evoke mechanical loading in hydrogel-based heart muscle engineering. PMID- 26362921 TI - Tumor microenvironment for cancer stem cells. AB - Tumor tissues consist of heterogeneous cancer cells including cancer stem cells (CSCs) that can terminally differentiate into cancer cells. Tissue-specific stem cells in normal organs maintain their stemness in a specific microenvironment, the stem cell niche; several studies have suggested that there are specific microenvironments that maintain CSCs in an immature phenotype. Cell types in a CSC niche vary from fibroblasts, to endothelial cells, immune cells, and so on; these non-cancer cells have been suggested to change their original features in the normal tissue/organ and to acquire a phenotype that protects CSCs from anticancer therapies. Therefore, to kill CSCs, we need to understand the cellular and molecular mechanisms involved in the maintenance of the immature phenotype of CSCs and in drug resistance. PMID- 26362922 TI - Metatranscriptomic discovery of plant biomass-degrading capacity from grass carp intestinal microbiomes. AB - Despite the economic importance of fish, the ecology and metabolic capacity of fish microbiomes are largely unknown. Here, we sequenced the metatranscriptome of the intestinal microbiota of grass carp, Ctenopharyngodon idellus, a freshwater herbivorous fish species. Our results confirmed previous work describing the bacterial composition of the microbiota at the phylum level as being dominated by Firmicutes, Fusobacteria, Proteobacteria and Bacteriodetes. Comparative transcriptomes of the microbiomes of fish fed with different experimental diets indicated that the bacterial transcriptomes are influenced by host diet. Although hydrolases and cellulosome-based systems predicted to be involved in degradation of the main chain of cellulose, xylan, mannan and pectin were identified, transcripts with glycoside hydrolase modules targeting the side chains of noncellulosic polysaccharides were more abundant. Predominant 'COG' (Clusters of Orthologous Group) categories in the intestinal microbiome included those for energy production and conversion, as well as carbohydrate and amino acid transport and metabolism. These results suggest that the grass carp intestinal microbiome functions in carbohydrate turnover and fermentation, which likely provides energy for both host and microbiota. Grass carp intestinal microbiome thus reflects its evolutionary adaption for harvesting nutrients for an herbivore with a high-throughput nutritional strategy that is not dominated by cellulose digestion but rather the degradation of intracellular polysaccharides. PMID- 26362923 TI - Assessing environmental drivers of microbial communities in estuarine soils of the Aconcagua River in Central Chile. AB - Aconcagua River basin (Central Chile) harbors diverse economic activities such as agriculture, mining and a crude oil refinery. The aim of this study was to assess environmental drivers of microbial communities in Aconcagua River estuarine soils, which may be influenced by anthropogenic activities taking place upstream and by natural processes such as tides and flood runoffs. Physicochemical parameters were measured in floodplain soils along the estuary. Bacteria, Actinobacteria, Alphaproteobacteria, Betaproteobacteria, Pseudomonas, Bacillus and Fungi were studied by DGGE fingerprinting of 16S rRNA gene and ribosomal ITS 1 amplified from community DNA. Correlations between environment and communities were assessed by distance-based redundancy analysis. Mainly hydrocarbons, pH and the composed variable copper/arsenic/calcium but in less extent nitrogen and organic matter/phosphorous/magnesium correlated with community structures at different taxonomic levels. Aromatic hydrocarbons degradation potential by bacterial community was studied. Polycyclic aromatic hydrocarbon ring hydroxylating dioxygenases genes were detected only at upstream sites. Naphthalene dioxygenase ndo genes were heterogeneously distributed along estuary, and related to Pseudomonas, Delftia, Comamonas and Ralstonia. IncP-1 plasmids were mainly present at downstream sites, whereas IncP-7 and IncP-9 plasmids showed a heterogeneous distribution. This study strongly suggests that pH, copper, arsenic and hydrocarbons are main drivers of microbial communities in Aconcagua River estuarine soils. PMID- 26362924 TI - Differentiation of 1-aminocyclopropane-1-carboxylate (ACC) deaminase from its homologs is the key for identifying bacteria containing ACC deaminase. AB - 1-Aminocyclopropane-1-carboxylate (ACC) deaminase-mediated reduction of ethylene generation in plants under abiotic stresses is a key mechanism by which bacteria can promote plant growth. Misidentification of ACC deaminase and the ACC deaminase structure gene (acdS) can lead to overestimation of the number of bacteria containing ACC deaminase and their function in ecosystems. Previous non specific amplification of acdS homologs has led to an overestimation of the horizontal transfer of acdS genes. Here, we designed consensus-degenerate hybrid oligonucleotide primers (acdSf3, acdSr3 and acdSr4) based on differentiating the key residues in ACC deaminases from those of homologs for specific amplification of partial acdS genes. PCR amplification, sequencing and phylogenetic analysis identified acdS genes from a wide range of proteobacteria and actinobacteria. PCR amplification and a genomic search did not find the acdS gene in bacteria belonging to Pseudomonas stutzeri or in the genera Enterobacter, Klebsiella or Bacillus. We showed that differentiating the acdS gene and ACC deaminase from their homologs was crucial for the molecular identification of bacteria containing ACC deaminase and for understanding the evolution of the acdS gene. We provide an effective method for screening and identifying bacteria containing ACC deaminase. PMID- 26362925 TI - Temperature dependences of growth rates and carrying capacities of marine bacteria depart from metabolic theoretical predictions. AB - Using the metabolic theory of ecology (MTE) framework, we evaluated over a whole annual cycle the monthly responses to temperature of the growth rates (MU) and carrying capacities (K) of heterotrophic bacterioplankton at a temperate coastal site. We used experimental incubations spanning 6oC with bacterial physiological groups identified by flow cytometry according to membrane integrity (live), nucleic acid content (HNA and LNA) and respiratory activity (CTC+). The temperature dependence of MU at the exponential phase of growth was summarized by the activation energy (E), which was variable (-0.52 to 0.72 eV) but followed a seasonal pattern, only reaching the hypothesized value for aerobic heterotrophs of 0.65 eV during the spring bloom for the most active bacterial groups (live, HNA, CTC+). K (i.e. maximum experimental abundance) peaked at 4 * 10(6) cells mL( 1) and generally covaried with MU but, contrary to MTE predictions, it did not decrease consistently with temperature. In the case of live cells, the responses of MU and K to temperature were positively correlated and related to seasonal changes in substrate availability, indicating that the responses of bacteria to warming are far from homogeneous and poorly explained by MTE at our site. PMID- 26362926 TI - Addressing the conundrum of multimorbidity in heart failure: Do we need a more strategic approach to improve health outcomes? AB - There is clear evidence across the globe that the clinical complexity of patients presenting to hospital with the syndrome of heart failure is increasing - not only in terms of the presence of concurrent disease states, but with additional socio-demographic risk factors that complicate treatment. Management strategies that treat heart failure as the main determinant of health outcomes ignores the multiple and complex issues that will inevitably erode the efficacy and efficiency of current heart failure management programmes. This complex problem (or conundrum) requires a different way of thinking around the complex interactions that underpin poor outcomes in heart failure. In this context, we present the COordinated NUrse-led inteNsified Disease management for continuity of caRe for mUltiMorbidity in Heart Failure (CONUNDRUM-HF) matrix that may well inform future research and models of care to achieve better health outcomes in this rapidly increasing patient population. PMID- 26362929 TI - Do young e-cigarette users become smokers? PMID- 26362930 TI - Dynamics of IL-4 and IL-13 expression in the airways of sheep following allergen challenge. AB - BACKGROUND: IL-4 and IL-13 play a critical yet poorly understood role in orchestrating the recruitment and activation of effector cells of the asthmatic response and driving the pathophysiology of allergic asthma. The house dust mite (HDM) sheep asthma model displays many features of the human condition and is an ideal model to further elucidate the involvement of these critical Th2 cytokines. We hypothesized that airway exposure to HDM allergen would induce or elevate the expression profile of IL-4 and IL-13 during the allergic airway response in this large animal model of asthma. METHODS: Bronchoalveolar lavage (BAL) samples were collected from saline- and house dust mite (HDM)- challenged lung lobes of sensitized sheep from 0 to 48 h post-challenge. BAL cytokines (IL-4, IL-13, IL-6, IL-10, TNF-alpha) were each measured by ELISA. IL-4 and IL-13 expression was assessed in BAL leukocytes by flow cytometry and in airway tissue sections by immunohistology. RESULTS: IL-4 and IL-13 were increased in BAL samples following airway allergen challenge. HDM challenge resulted in a significant increase in BAL IL-4 levels at 4 h compared to saline-challenged airways, while BAL IL-13 levels were elevated at all time-points after allergen challenge. IL-6 levels were maintained following HDM challenge but declined after saline challenge, while HDM administration resulted in an acute elevation in IL-10 at 4 h but no change in TNF-alpha levels over time. Lymphocytes were the main early source of IL-4, with IL-4 release by alveolar macrophages (AMs) prominent from 24 h post allergen challenge. IL-13 producing AMs were increased at 4 and 24 h following HDM compared to saline challenge, and tissue staining provided evidence of IL-13 expression in airway epithelium as well as immune cells in airway tissue. CONCLUSION: In a sheep model of allergic asthma, airway inflammation is accompanied by the temporal release of key cytokines following allergen exposure that primarily reflects the Th2-driven nature of the immune response in asthma. The present study demonstrates for the first time the involvement of IL-4 and IL 13 in a relevant large animal model of allergic airways disease. PMID- 26362931 TI - Autophagy as a defense strategy against stress: focus on Paracentrotus lividus sea urchin embryos exposed to cadmium. AB - Autophagy is used by organisms as a defense strategy to face environmental stress. This mechanism has been described as one of the most important intracellular pathways responsible for the degradation and recycling of proteins and organelles. It can act as a cell survival mechanism if the cellular damage is not too extensive or as a cell death mechanism if the damage/stress is irreversible; in the latter case, it can operate as an independent pathway or together with the apoptotic one. In this review, we discuss the autophagic process activated in several aquatic organisms exposed to different types of environmental stressors, focusing on the sea urchin embryo, a suitable system recently included into the guidelines for the use and interpretation of assays to monitor autophagy. After cadmium (Cd) exposure, a heavy metal recognized as an environmental toxicant, the sea urchin embryo is able to adopt different defense mechanisms, in a hierarchical way. Among these, autophagy is one of the main responses activated to preserve the developmental program. Finally, we discuss the interplay between autophagy and apoptosis in the sea urchin embryo, a temporal and functional choice that depends on the intensity of stress conditions. PMID- 26362932 TI - Tribenuron-Methyl Induces Male Sterility through Anther-Specific Inhibition of Acetolactate Synthase Leading to Autophagic Cell Death. AB - Tribenuron-methyl (TM) is a powerful sulfonylurea herbicide that inhibits branched-chain amino acid (BCAA) biosynthesis by targeting the catalytic subunit (CSR1) of acetolactate synthase (ALS). Selective induction of male sterility by foliar spraying of TM at low doses has been widely used for hybrid seed production in rapeseed (Brassica napus); however, the underlying mechanism remains unknown. Here, we report greater TM accumulation and subsequent stronger ALS inhibition and BCAA starvation in anthers than in leaves and stems after TM application. Constitutive or anther-specific expression of csr1-1D (a CSR1 mutant) eliminated anther-selective ALS inhibition and reversed the TM-induced male sterile phenotype in both rapeseed and Arabidopsis. The results of TM daub stem experiments, combined with the observations of little TM accumulation in anthers and reversion of TM-induced male sterility by targeted expression of the TM metabolism gene Bel in either the mesophyll or phloem, suggested that foliar sprayed TM was polar-transported to anthers mainly through the mesophyll and phloem. Microscopy and immunoblotting revealed that autophagy, a bulk degradation process induced during cell death, was elevated in TM-induced male sterile anthers and by anther-specific knockdown of ALS. Moreover, TM-induced pollen abortion was significantly inhibited by the autophagy inhibitor 3-MA. These data suggested that TM was polar-transported to anthers, resulting in BCAA starvation via anther-specific ALS inhibition and, ultimately, autophagic cell death in anthers. PMID- 26362933 TI - Erratum to: Prevalence of tetracycline resistance genes among multi-drug resistant bacteria from selected water distribution systems in southwestern Nigeria. PMID- 26362934 TI - Long Noncoding RNAs as Targets and Regulators of Nuclear Receptors. AB - Intensive research has been directed at the discovery, biogenesis, and expression patterns of long noncoding RNAs , yet their biochemical functions have remained elusive for the most part. Nuclear receptors that interpret signaling mediated by small molecule hormones play a role in regulating the expression of some long noncoding RNAs. More importantly, these RNAs have also been shown to effect hormone-affected gene transcription regulated by the nuclear receptors. In this chapter, we summarize the current knowledge that has been acquired on hormonal signaling inducing expression of long noncoding RNAs and how they then may act in trans or in cis to modulate gene transcription. We highlight a few of these noncoding RNA molecules in terms of how they may impact hormone-driven cancers. Future directions critical for moving this field forward are presented, with a clear emphasis on the need for better biochemical approaches to address the mechanism of action of these exciting RNAs. PMID- 26362935 TI - The Memory Function of the B Cell Antigen Receptor. AB - Activated B lymphocytes preserve their antigen experience by differentiating into long-lived pools of antibody-secreting plasma cells or various types of memory B cells (MBCs). The former population constantly produces serum immunoglobulins with sufficient specificity and affinity to thwart infections with recurrent pathogens. By contrast, memory B cell populations retain their antigen receptors on the cell surface and hence need pathogen-induced differentiation steps before they can actively contribute to host defense. The terminal differentiation of MBCs into antibody-secreting plasma cells is hallmarked by the absence of the lag phase characteristic for primary antibody responses. Moreover, secondary antibody responses are predominantly driven by MBCs that bear an antigen receptor of the IgG class on their surface although IgM-positive memory populations exist as well. These fundamental principles of B cell memory were enigmatic for decades. Only recently, we have begun to understand the underlying mechanisms. This review summarizes our current understanding of how different subpopulations of MBCs are generated during primary immune responses and how their functional heterogeneity on antigen recall is controlled by different signaling capabilities of B cell antigen receptor (BCR) isotypes and by the nature of the antigen. PMID- 26362936 TI - GPs' income fell 3% in a year, UK data show. PMID- 26362937 TI - Assessing the capacity to diagnose human African trypanosomiasis among health care personnel from Chama and Mambwe districts of eastern Zambia. AB - BACKGROUND: Human African Trypanosomiasis (HAT) is a neglected tropical disease affecting poor rural communities living in tsetse-infested regions of sub-Saharan Africa. In Zambia, sporadic cases of HAT have been reported mainly in the old foci along the tsetse-infested Luangwa river valley in north-eastern part of the country. In such places where malaria is the major endemic febrile disease, with possibilities of co-infections of HAT and malaria and where the levels of alertness to the presence of HAT among health care personnel (HCP) is low, there is a high chance of misdiagnosing HAT for malaria because of their similarities in clinical presentation. This study, conducted in Zambia's tsetse-infested rural health centres (RHCs) of Chama and Mambwe districts, was designed to investigate the staffing levels, the HCP levels of alertness to the occurrence of HAT and their capacity to detect the disease. METHODS: Structured questionnaires were used to collect information pertaining to HAT alertness and the capacity to detect the disease from 101 HCP in a cross sectional study of 23 RHCs drawn from Zambia's Chama and Mambwe districts between April and July 2013. The data collected were analyzed using Stata/SE version 11.0. RESULTS: Participants from both Chama and Mambwe district RHCs reported similar very low levels of qualified HCP and laboratory technicians, and that they had similar basic tools for HAT diagnosis. Although not statistically significant, respondents from Chama (~89%) tended to be more aware about the occurrence of HAT compared to their Mambwe counterparts (~78%). Whereas ~40% of the HCP from Chama district (n = 52) claimed to have encountered at least one case of HAT, only ~4% of their Mambwe counterparts (n = 49) had similar experiences (P = 0.000). CONCLUSION: Health care personnel in RHCs from Chama tended to be more alert to the occurrence of HAT than the HCP from Mambwe district. The extremely low levels of categorized HCP, general absence of functional laboratories, coupled with absence of national HAT surveillance and control programs, are among some of the serious challenges that Zambia's Chama and Mambwe districts face to control/eliminate HAT. PMID- 26362939 TI - Comparison of Fe-Al-modified natural materials by an electrochemical method and chemical precipitation for the adsorption of F- and As(V). AB - The adsorption of fluoride and arsenic ions by modified natural materials may have an impact on the removal of F- and As(V) from waters. In this work, a zeolitic material and pozzolan (commonly known as pumicite) were modified with aluminium an iron by an electrochemical method and chemical precipitation, respectively. The adsorbents were characterized by X-ray diffraction, scanning electron microscopy with energy X-ray disperse spectroscopy analysis and the point of zero charge (pHzpc). F- and As(V) adsorption properties of both materials were investigated. Adsorption kinetic data were best fitted to pseudo second-order model and equilibrium data to the Langmuir isotherm model. The highest F- and As(V) sorption capacities were obtained for modified zeolitic (0.866 mg/g) and pozzolan (3.35 mg/g) materials, respectively, with initial F- or As(V) concentrations of 10 mg/L. It was found that the unmodified materials did not show either adsorption of F- ions or As(V), which indicated that Al and Fe in the adsorbents are responsible for the adsorption of these ions. In general, both modified materials show similar capacities for the adsorption of F- and As(V). PMID- 26362938 TI - Expression and clinical significance of annexin A2 and human epididymis protein 4 in endometrial carcinoma. AB - BACKGROUND: It is well-known that the treatment and monitoring methods are limited for advanced stage of endometrial carcinoma. Biological molecules with expression changes during tumor progression become potential therapeutic targets for advanced stage endometrial carcinoma. Annexin A2 (ANXA2) has been reported to be overexpressed in recurrent endometrial carcinoma, and the expression of human epididymis protein 4 (HE4) is upregulated in endometrial carcinoma. What's more, ANXA2 and HE4 interacted in ovarian cancer and promoted the malignant biological behavior. We speculated that their interaction may exist in endometrial carcinoma as well. We evaluated the expression and the correlation relationship of ANXA2 and HE4 in endometrial carcinoma. METHODS: The expression of ANXA2 and HE4 protein in 84 endometrial carcinoma, 30 endometrial atypical hyperplasia, and 18 normal endometrial tissue samples were then measured using an immunohistochemical assay in paraffin embedded endometrial tissues. The structural relationship between ANXA2 and HE4 was explored by immunoprecipitation and double immunofluorescent staining. RESULTS: ANXA2 and HE4 co-localized in both endometrial tissues and endometrial carcinoma cells. ANXA2 and HE4 were expressed in 95.2 % and 85.7 % of the the endometrial carcinoma, respectively, which were significantly higher than normal endometrium (55.6 % and 16.7 %, both p < 0.05). The expression of ANXA2 and HE4 was significantly correlated with FIGO stage, degree of differentiation, myometrial invasion, and lymph node metastasis. ANXA2 was an independent risk factor for the prognosis of endometrial carcinoma (p < 0.05, hazard ratio [HR] = 8.004). The expression of ANXA2 and HE4 was positively correlated (Spearman correlation coefficient = 0.228, p < 0.05). HE4 was an independent factor for ANXA2 in multivariate linear regression model (p < 0.05). CONCLUSION: We revealed the co-localization of ANXA2 and HE4 in endometrial carcinoma. Expression levels of ANXA2 and HE4 were closely related to the malignant biological behavior of endometrial carcinoma, and ANXA2 was an independent risk factor for poor prognosis. The expression of ANXA2 and HE4 can affect each other. PMID- 26362940 TI - Long term outcomes of cemented endoprosthetic reconstruction for periarticular tumors of the distal femur. AB - BACKGROUND: In order to achieve an oncological margin during limb salvage surgery for tumors of the distal femur, part or the entire knee joint is frequently sacrificed. Endoprosthetics make limb salvage possible through restoration of a functional extremity. Currently there remains a paucity of data concerning their long-term outcomes and associated risk factors for failure. METHODS: We identified 152 patients who underwent an endoprosthetic reconstruction for an oncological process of the distal femur between 1972 and 2013. The mean follow-up was 10years. Mean age and body mass index (BMI) were 39years and 25.8 respectively. The most common pathology was osteosarcoma (n=78, 48%). Outcomes were compared to a control group of 20,643 patients undergoing total knee arthroplasty (TKA) for degenerative joint disease (DJD) during the same time period. RESULTS: The mean five-, 10-, 15-, 20-, and 25-year revision-free survival for an endoprosthesis was 76%, 63%, 51%, 36%, and 28%. Compared to the five-, 10-, 15-, 20-, and 25-year survival of 95%, 90%, 82%, 74%, and 67% for control TKAs (p<0.0001 at all-time points). Overall limb survival was 93%, with 11 patients undergoing amputation. There was no difference in implant survival comparing modular and custom endoprostheses. CONCLUSION: The results of this study show that given the complexity of these operations, the rate of revision surgery following endoprosthetic replacement is high. Nevertheless, the use of these modular reconstructions leads to a high rate of limb salvage (93%) over a 25-year period at our institution. LEVEL OF EVIDENCE: Level III. PMID- 26362941 TI - Motor and extra-motor gray matter atrophy in amyotrophic lateral sclerosis: quantitative meta-analyses of voxel-based morphometry studies. AB - Considerable evidence from previous voxel-based morphometry studies indicates widespread but heterogeneous gray matter (GM) deficits in amyotrophic lateral sclerosis (ALS). Here, we aimed to investigate the concurrence across voxel-based morphometry studies to help clarify the spatial pattern of GM abnormalities that underlie this condition. Comprehensive meta-analyses to assess regional GM anomalies in ALS were conducted with the Anisotropic Effect Size version of Signed Differential Mapping software package. Twenty studies, which reported 22 comparisons and were composed of 454 ALS patients and 426 healthy controls, were included in the meta-analyses. Regional GM atrophy in ALS was consistently found in the frontal, temporal, and somatosensory areas. Meta-regression demonstrated that the disease duration, disease severity, and age were significantly related to GM deficits in ALS patients. The present meta-analysis provides convergent evidence that ALS is a multisystem degenerative disorder that is accompanied by a unique and widespread pattern of robust cortical GM atrophy. Future studies should investigate whether this atrophy pattern is a diagnostic and prognostic marker. PMID- 26362942 TI - Endocannabinoid regulation of amyloid-induced neuroinflammation. AB - The modulation of endocannabinoid (EC) levels and the activation of cannabinoid receptors are seen as promising therapeutic strategies in a variety of diseases, including Alzheimer's disease (AD). We aimed to evaluate the effect of the pharmacologic and genetic inhibition of anandamide-degrading enzyme in a mouse model of AD (5xFAD). Pharmacologic inhibition of the fatty acid amide hydrolase (FAAH) had little impact on the expression of key enzymes and cytokines and also on the cognitive impairment, plaque deposition, and gliosis in 5xFAD mice. CB1 blockade exacerbated inflammation in this transgenic mouse model of AD. The genetic inactivation of FAAH led to increases in the expression of inflammatory cytokines. At the same time, FAAH-null 5xFAD mice exhibited a behavioral improvement in spatial memory that was independent of the level of anxiety and was not CB1 mediated. Finally, mice lacking FAAH showed diminished soluble amyloid levels, neuritic plaques, and gliosis. These data reinforce the notion of a role for the EC system in neuroinflammation and open new perspectives on the relevance of modulating EC levels in the inflamed brain. PMID- 26362943 TI - De novo FUS mutations are the most frequent genetic cause in early-onset German ALS patients. AB - In amyotrophic lateral sclerosis (ALS) patients with known genetic cause, mutations in chromosome 9 open reading frame 72 (C9orf72) and superoxide dismutase 1 (SOD1) account for most familial and late-onset sporadic cases, whereas mutations in fused in sarcoma (FUS) can be identified in just around 5% of familial and 1% of overall sporadic cases. There are only few reports on de novo FUS mutations in juvenile ALS patients. To date, no systematic evaluation on the frequency of de novo FUS mutations in early-onset ALS patients has been conducted. Here, we screened a cohort of 14 early-onset sporadic ALS patients (onset age <35 years) to determine the frequency of mutations in C9orf72, SOD1, and FUS in this defined patient cohort. All patients were recruited prospectively by a single center in a period of 38 months. No mutations were detected in SOD1 or C9orf72; however, we identified 6 individuals (43%) carrying a heterozygous FUS mutation including 1 mutation that has not been described earlier (c.1504delG [p.Asp502Thrfs*27]). Genetic testing of parents was possible in 5 families and revealed that the mutations in these patients arose de novo. Three of the 6 identified patients presented with initial bulbar symptoms. Our study identifies FUS mutations as the most frequent genetic cause in early-onset ALS. Genetic testing of FUS thus seems indicated in sporadic early-onset ALS patients especially if showing predominant bulbar symptoms and an aggressive disease course. PMID- 26362945 TI - Haemophilus influenzae strains possess variations in the global transcriptional profile in response to oxygen levels and this influences sensitivity to environmental stresses. AB - An alcohol dehydrogenase, AdhC, is required for Haemophilus influenzae Rd KW20 growth with high oxygen. AdhC protects against both exogenous and metabolically generated, endogenous reactive aldehydes. However, adhC in the strain 86-028NP is a pseudogene. Unlike the Rd KW20 adhC mutant, 86-028NP does grow with high oxygen. This suggests the differences between Rd KW20 and 86-028NP include broader pathways, such as for the maintenance of redox and metabolism that avoids the toxicity related to oxygen. We hypothesized that these differences affect their resistance to relevant toxic chemicals, including reactive aldehydes. Across a range of oxygen concentrations, despite the growth profiles of Rd KW20 and 86-028NP being similar, there was a significant variation in their sensitivity to reactive aldehydes. 86-028NP is more sensitive to methylglyoxal, formaldehyde and glycolaldehyde under high oxygen than low oxygen as well as compared to Rd KW20. Also, as oxygen levels changed the whole genome gene expression profiles of Rd KW20 and 86-028NP revealed distinctions in their transcriptomes (the iron, FNR and ArcAB regulons). These were indicative of a difference in their intracellular redox properties and we show it is this that underpins their survival against reactive aldehydes. PMID- 26362944 TI - Assessing efficacy of different nucleos(t)ide backbones in NNRTI-containing regimens in the Swiss HIV Cohort Study. AB - BACKGROUND: The most recommended NRTI combinations as first-line antiretroviral treatment for HIV-1 infection in resource-rich settings are tenofovir/emtricitabine, abacavir/lamivudine, tenofovir/lamivudine and zidovudine/lamivudine. Efficacy studies of these combinations also considering pill numbers, dosing frequencies and ethnicities are rare. METHODS: We included patients starting first-line combination ART (cART) with or switching from first line cART without treatment failure to tenofovir/emtricitabine, abacavir/lamivudine, tenofovir/lamivudine and zidovudine/lamivudine plus efavirenz or nevirapine. Cox proportional hazards regression was used to investigate the effect of the different NRTI combinations on two primary outcomes: virological failure (VF) and emergence of NRTI resistance. Additionally, we performed a pill burden analysis and adjusted the model for pill number and dosing frequency. RESULTS: Failure events per treated patient for the four NRTI combinations were as follows: 19/1858 (tenofovir/emtricitabine), 9/387 (abacavir/lamivudine), 11/344 (tenofovir/lamivudine) and 45/1244 (zidovudine/lamivudine). Compared with tenofovir/emtricitabine, abacavir/lamivudine had an adjusted HR for having VF of 2.01 (95% CI 0.86-4.55), tenofovir/lamivudine 2.89 (1.22-6.88) and zidovudine/lamivudine 2.28 (1.01-5.14), whereas for the emergence of NRTI resistance abacavir/lamivudine had an HR of 1.17 (0.11-12.2), tenofovir/lamivudine 11.3 (2.34-55.3) and zidovudine/lamivudine 4.02 (0.78-20.7). Differences among regimens disappeared when models were additionally adjusted for pill burden. However, non-white patients compared with white patients and higher pill number per day were associated with increased risks of VF and emergence of NRTI resistance: HR of non-white ethnicity for VF was 2.85 (1.64-4.96) and for NRTI resistance 3.54 (1.20-10.4); HR of pill burden for VF was 1.41 (1.01-1.96) and for NRTI resistance 1.72 (0.97-3.02). CONCLUSIONS: Although VF and emergence of resistance was very low in the population studied, tenofovir/emtricitabine appears to be superior to abacavir/lamivudine, tenofovir/lamivudine and zidovudine/lamivudine. However, it is unclear whether these differences are due to the substances as such or to an association of tenofovir/emtricitabine regimens with lower pill burden. PMID- 26362946 TI - Increasing gender and ethnic diversity in the health care workforce: The case of Arab male nurses in Israel. AB - BACKGROUND: Despite recent attempts at increasing health care workforce diversity, a measure that was found to reduce health disparities, men remain a minority in the traditionally female occupation of nursing. One exception to this observation is the Arab ethnic minority in Israel that includes numerous male nurses. OBJECTIVE: Determining the percentage of Arab male nurses in the Israeli health care system and understanding how they perceive and negotiate their masculinity. METHODOLOGY: We used both quantitative and qualitative methodologies. Quantitative statistics were obtained from the 2011 to 2013 Labor Force Survey conducted by the Israel Central Bureau of Statistics and qualitative data derived from 13 semi-structured, in-depth interviews with Arab nurses working in Israeli public hospitals, conducted during 2014. FINDINGS: Nursing constitutes a prominent employment path for Arab men in Israel and is more prominent as an employment path for Arab men than that for Jewish men. A total of 38.6% of all Arab nurses were men and only 7.5% of Jews and others. Quantitative data thus reveal that men do not constitute a minority among Arab nurses. Similarly, qualitative findings show that Arab male nurses do not manifest marginal masculinity but rather demonstrate many elements of hegemonic masculinity. Arab male nurses distinguish themselves and differentiate their roles from those of female nurses, expressing their motives for choosing the nursing profession in terms of hegemonic gender roles for men in Arab society in Israel. CONCLUSIONS: Although nursing is a traditionally female occupation, it offers an opportunity for Arab men to demonstrate their masculinity. Arab male nurses choose nursing as a means rather than an end, however, meaning that many of them might not remain in the profession. This observation is significant because of the importance of retaining men from ethnic minorities in nursing, especially in multicultural societies. PMID- 26362948 TI - Effect of Shift Work on Nocturia. AB - OBJECTIVE: To identify the circadian sensitive component of nocturia by comparing nocturia in patients who voluntarily choose a disrupted circadian rhythm, that is, shift workers, with those who maintain normal day-night cycles. MATERIALS AND METHODS: Between 2011 and 2013, a total of 1741 untreated patients, 1376 nonshift workers and 365 shift workers, were compared for nocturia indices based on frequency volume charts (FVCs). General linear model of 8-hour interval urine production and frequency were compared between FVCs of nonshift workers, FVCs of night-shift workers, and FVCs of day-shift workers. RESULTS: Nocturia frequency was increased in the night-shift workers (2.38 +/- 1.44) compared with nonshift workers (2.18 +/- 1.04) (P <.01). Whereas nocturnal polyuria index did not increase significantly (0.33 +/- 0.19 for night-shift workers, 0.34 +/- 0.13 for nonshift workers, P = .24), nocturnal bladder capacity index increased significantly (1.41 +/- 1.06 for night-shift workers, 1.26 +/- 0.92 for nonshift workers, P <.01). Eight-hour interval indices show that urine production changed with shift (P <.01), whereas voiding frequency remains unchanged despite shift changes (P = .35). CONCLUSION: Patients in alternating work shifts showed increased nocturia, especially during their night shift. These changes tended to be more associated with decreased nocturnal bladder capacity than increased nocturnal polyuria. PMID- 26362947 TI - New Chronic Kidney Disease and Overall Survival After Nephrectomy for Small Renal Cortical Tumors. AB - OBJECTIVE: To evaluate kidney functional and overall survival (OS) outcomes in a cohort of patients who underwent partial nephrectomy (PN) or radical nephrectomy (RN) for tumors <=4 cm. MATERIALS AND METHODS: We performed a retrospective study on 2110 patients who underwent PN or RN with normal contralateral kidneys and normal serum creatinine from 1989 through 2012. Estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Primary end points were baseline incidence of CKD, OS, and new onset of eGFR <=60 and <=45 mL/min/1.73 m(2). RESULTS: Preoperatively, 30% and 8% of the cohort had eGFR <=60 and <=45 mL/min/1.73 m(2), respectively. Five-year freedom from eGFR <=60 mL/min/1.73 m(2) was 24% (95% confidence interval [CI], 19%-30%) and 76% (95% CI, 72%-78%) for RN and PN, respectively, and 5-year freedom from eGFR <=45 mL/min/1.73 m(2) was 51% (95% CI, 45%-56%) and 91% (95% CI, 89%-93%) for RN and PN, respectively. On multivariable analysis, hazard ratio for RN vs PN was 4.98 (95% CI, 4.11-6.04, P <.0001) for new onset of eGFR <=60 mL/min/1.73 m(2) and 9.28 (95% CI, 7.26-11.86, P <.0001) for new onset of eGFR <=45 mL/min/1.73 m(2). The RN group had a higher rate of death per year than the partial group (hazard ratio = 1.61, 95% CI, 1.24-2.08, P = .0003). CONCLUSION: The present study confirms published works demonstrating that a significant proportion of patients have pre-existing CKD. In patients with normal kidney function, RN is associated with a significantly higher risk for developing CKD and worse OS than PN. PMID- 26362949 TI - Post-traumatic High-flow Priapism: Multidetector Computed Tomography Demonstration. AB - High-flow priapism due to pseudoaneurysm is a relatively rare urologic condition. Clear anatomic delineation of the number and origin of feeding vessels facilitates pre-embolization planning. Computed tomographic angiography can afford a three-dimensional display of the feeding vessels. We present a 26-year old man with post-traumatic high-flow priapism, which is the first case studied with computed tomographic angiography. PMID- 26362950 TI - Identification of Spermatogenically Active Regions in Rat Testes by Using Narrow band Imaging System. AB - OBJECTIVE: To evaluate the feasibility of narrow-band imaging (NBI) system in microdissection testicular sperm extraction (micro-TESE). MATERIALS AND METHODS: Firstly, we investigated angiogenic potential in human testicular specimens obtained from 48 patients who underwent micro-TESE. We then created a testicular injury model in rats with a single topical injection of cisplatin into the testes, and the testes were observed with and without NBI. To assess the relation between pathological changes and visual images, an immunofluorescence study of blood vessels in rat testes was carried out. We finally conducted an experiment that assumed micro-TESE by using a nonobstructive azoospermia (NOA) rat model induced by busulfan. RESULTS: The number of blood vessels in the specimens of hypospermatogenesis was significantly greater than that in the specimens of maturation arrest and Sertoli cell only. In rat testes, cisplatin caused atrophic changes, and significant differences in visual color between atrophic and normal lesions were noted using NBI. The number of seminiferous tubules with spermatozoa in atrophic regions was significantly lower than that in normal regions, and a significantly small number of blood vessels in atrophic regions was also noted compared with that in normal regions. NBI also identified patchy spermatogenesis in the busulfan-induced NOA rat model. CONCLUSION: An NBI system can distinguish spermatogenically active regions through the visualization of blood vessels in rat testes. This system may have the potential to provide useful information during micro-TESE for men with NOA. PMID- 26362951 TI - Molecular epidemiology of multidrug-resistant Acinetobacter baumannii isolates in a university hospital in Nepal reveals the emergence of a novel epidemic clonal lineage. AB - The emergence of multidrug-resistant (MDR) Acinetobacter baumannii has become a serious medical problem worldwide. To clarify the genetic and epidemiological properties of MDR A. baumannii strains isolated from a medical setting in Nepal, 246 Acinetobacter spp. isolates obtained from different patients were screened for MDR A. baumannii by antimicrobial disk susceptibility testing. Whole genomes of the MDR A. baumannii isolates were sequenced by MiSeqTM (Illumina), and the complete genome of one isolate (IOMTU433) was sequenced by PacBio RS II. Phylogenetic trees were constructed from single nucleotide polymorphism concatemers. Multilocus sequence types were deduced and drug resistance genes were identified. Of the 246 Acinetobacter spp. isolates, 122 (49.6%) were MDR A. baumannii, with the majority being resistant to aminoglycosides, carbapenems and fluoroquinolones but not to colistin and tigecycline. These isolates harboured the 16S rRNA methylase gene armA as well as bla(NDM-1), bla(OXA-23) or bla(OXA 58). MDR A. baumannii isolates belonging to clonal complex 1 (CC1) and CC2 as well as a novel clonal complex (CC149) have spread throughout a medical setting in Nepal. The MDR isolates harboured genes encoding carbapenemases (OXA and NDM 1) and a 16S rRNA methylase (ArmA). PMID- 26362952 TI - Defining renal recovery: pitfalls to be avoided. PMID- 26362953 TI - Severe hypercoagulable state on veno-arterial extracorporeal membrane oxygenation. PMID- 26362954 TI - Infants Perceive Three-Dimensional Illusory Contours as Occluding Surfaces. AB - The study assessed the contribution of stereoscopic depth cues to infants' perception of a Kanizsa rectangle as a surface that temporarily occludes a moving object. In Experiment 1, the Kanizsa figure was shifted into the foreground by enriching it with stereoscopic depth information. According to the results, perception of a three-dimensional Kanizsa figure as an occluding surface emerges between 5 (n = 16) and 7 (n = 16) months of age. Experiment 2 demonstrated that 7 month-old (n = 16) infants performed similarly to the 7-month-olds who participated in Experiment 1 if the moving object was shifted into the background. These findings suggest that 7-month-old infants respond to stereoscopic depth cues and that they exploit it to perceive subjective contours as occluders. PMID- 26362955 TI - Neurorehabilitation for Parkinson's disease: Future perspectives for behavioural adaptation. AB - Parkinson's disease is a common neurodegenerative disorder, resulting in both motor and non-motor symptoms that significantly reduce quality of life. Treatment consists of both pharmaceutical and non-pharmaceutical treatment approaches. Neurorehabilitation is an important non-pharmaceutical treatment approach, and a prime component of this is formed by the training of behavioural adaptations that can assist patients to cope better with their motor and non-motor symptoms. Optimal delivery of neurorehabilitation requires a tailor-made, personalized approach. In this review we discuss the great potential for growth in the field of neurorehabilitation. Specifically, we will focus on four relatively new developments: visual rehabilitation (because Parkinson patients are very dependent on optimal vision); cueing delivered by wearable devices (allowing for objective, continuous, and quantitative detection of mobility problems, such that cueing can be delivered effectively in an on-demand manner - i.e., with external cues being delivered only at a time when they are needed most); exergaming (to promote compliance with exercise programs); and telemedicine (allowing for delivery of expert rehabilitation advice to the patient's own home). Evidence in these new fields is growing, based on good clinical trials, fuelling hope that state-of-the-art neurorehabilitation can make a real impact on improving the quality of life of patients affected by Parkinson's disease. PMID- 26362957 TI - The protective effects of tadalafil on renal damage following ischemia reperfusion injury in rats. AB - Ischemia-reperfusion injury can cause renal damage, and phosphodiesterase inhibitors are reported to regulate antioxidant activity. We investigated the prevention of renal damage using tadalafil after renal ischemia reperfusion (I/R) injury in rats. A total of 21 adult male Wistar albino rats were randomly divided into three groups of seven, including Group 1-control, Group 2-I/R, and Group 3 tadalafil + I/R group (I/R-T group) received tadalafil intraperitoneally at 30 minutes before ischemia. Inducible nitric oxide synthase, endothelial nitric oxide synthase, malondialdehyde, and total antioxidant capacity levels were evaluated, and histopathological changes and apoptosis in the groups were examined. Tadalafil decreased malondialdehyde levels in the I/R group and increased the total antioxidant capacity level. Histopathological and immunohistochemical findings revealed that tadalafil decreased renal injury scores and the ratios of injured cells, as measured through apoptotic protease activating factor 1, inducible nitric oxide synthase, and endothelial nitric oxide synthase levels. We suggest that tadalafil has protective effects against I/R-related renal tissue injury. PMID- 26362956 TI - Risk group characteristics and viral transmission clusters in South-East Asian patients infected with human immunodeficiency virus-1 (HIV-1) circulating recombinant form (CRF) 01_AE and subtype B. AB - Human immunodeficiency virus (HIV)-1 epidemics in Asian countries are driven by varying exposures. The epidemiology of the regional pandemic has been changing with the spread of HIV-1 to lower-risk populations through sexual transmission. Common HIV-1 genotypes include subtype B and circulating recombinant form (CRF) 01_AE. Our objective was to use HIV-1 genotypic data to better quantify local epidemics. TASER-M is a multicenter prospective cohort of HIV-infected patients. Associations between HIV exposure, patient sex, country of sample origin and HIV 1 genotype were evaluated by multivariate logistic regression. Phylogenetic methods were used on genotypic data to investigate transmission relationships. A total of 1086 patients from Thailand, Hong Kong, Malaysia and the Philippines were included in analyses. Proportions of male patients within countries varied (Thailand: 55.6%, Hong Kong: 86.1%, Malaysia: 81.4%, Philippines: 93.8%; p < 0.001) as did HIV exposures (heterosexual contact: Thailand: 85.7%, Hong Kong, 46.2%, Malaysia: 47.8%, Philippines: 25.0%; p < 0.001). After adjustment, we found increased subtype B infection among men who have sex with men, relative to heterosexual-reported exposures (odds ratio = 2.4, p < 0.001). We further describe four transmission clusters of eight to 15 treatment naive, predominantly symptomatic patients (two each for subtype B and CRF01_AE). Risk-group subpopulations differed with respect to the infecting HIV-1 genotype. Homosexual exposure patients had higher odds of being infected with subtype B. Where HIV-1 genotypes circulate within countries or patient risk-groups, local monitoring of genotype-specific transmissions may play a role in focusing public health prevention strategies. Phylogenetic evaluations provide complementary information for surveillance and monitoring of viruses with high mutation rates such as HIV-1 and Ebola. PMID- 26362958 TI - Effects of sugammadex on the prevention of postoperative peritoneal adhesions. AB - Many materials and techniques have been used to prevent and repair intra abdominal adhesions, but an effective solution has not been found. The aim of this study is to research the effect of sugammadex on intra-abdominal adhesions in an experimentally induced intra-abdominal adhesion model. Twenty-four female Wistar albino rats were included in the study. The experimental animals were randomly divided into three groups: the sugammadex group (Group SX, n = 8), the control group (Group C, n = 8), and the sham group (Group S, n = 8). After starvation for 1 night, the rats were injected with a 50 mg/kg intramuscular dose of ketamine and a 5 mg/kg intramuscular dose of xylazine for anesthesia. The rats in the SX group were given 3 mL sugammadex into the peritoneal cavity, while rats in the control group were given 3 mL 0.9% sodium chloride. In the sham group, the peritoneal cavity was opened, but no chemicals were administered. All rats were sacrificed on the 10(th) postoperative day. The adhesions were staged as 0, 1, 2, and 3 according to Evans et al.'s model. Our evaluation of macroscopic adhesion intensity found statistically significant differences between the groups. The sugammadex group was observed to have fewer adhesions in a statistically significant manner compared with the control group (p < 0.05). In our experimental intra-abdominal adhesion model in rats, we observed that sugammadex prevented postoperative intra-abdominal adhesions. PMID- 26362959 TI - Comparison of the postoperative analgesic effects of paracetamol-codeine phosphate and naproxen sodium-codeine phosphate for lumbar disk surgery. AB - The aim of this study was to compared the efficacy of paracetamol-codeine phosphate and naproxen sodium-codeine phosphate on postoperative pain and tramadol consumption during the first 24 hours after a lumbar disk surgery. After Ethics Committee approval and informed consent had been obtained, 64 patients were allocated into three groups. Patients received oral paracetamol-codeine (300 mg + 30 mg; Group P), naproxen sodium-codeine (550 mg + 30 mg; Group N), or placebo tablets (Group C) 30 minutes prior to induction of anesthesia. Patient controlled analgesia was supplied postoperatively using tramadol. Pain intensity, tramadol consumption, and side effects were recorded every 1 hour, 2 hours, 6 hours, 12 hours, and 24 hours after surgery. Whole study period pain intensity (visual analogue scale scores) was lower in Group P (p = 0.007) and Group N (p = 0.001), compared with Group C, however, there was no statistically significant difference between Group P and Group N regarding pain intensity (p > 0.05). Tramadol consumption was lower in Group P and Group N, compared with Group C (p < 0.001), and in turn the lowest incidence of tramadol consumption was detected in Group P compared with Group N (p < 0.001) and Group C (p < 0.001). Side effects were similar between the groups. Preemptive administration of paracetamol-codeine and naproxen sodium-codeine combination significantly reduced tramadol consumption and provided more effective analgesia compared with placebo. The paracetamol-codeine combination was superior to naproxen sodium-codeine with regard to tramadol consumption. PMID- 26362960 TI - Titanium Elastic Nail versus plate fixation of displaced midshaft clavicle fractures: A retrospective comparison study. AB - This study has two purposes: (1) to compare the clinical results between the Titanium Elastic Nail (TEN) and plate fixation of the displaced midshaft clavicle fracture; and (2) to demonstrate the relationship between length shortening and functional outcome after TEN fixation, especially in the comminuted fracture pattern. A retrospective, case-controlled study was conducted and 55 patients were included in our study: 25 in the TEN fixation group (TEN group) and 30 in the plate fixation group (plate group). All patients were classified into four subgroups: simple fracture in the TEN group (ST; n = 13), simple fracture in the plate group (SP; n = 15), comminuted fracture in the TEN group (CT; n = 12), and comminuted fracture in the plate group (CP; n = 15). Wound size was significantly smaller in the TEN group (p < 0.001). The injured clavicular length after fracture healing was significantly shorter in the TEN group (p = 0.036). There was no significant difference in the mean Constant and DASH scores. Injured clavicle shortening was significantly larger in the CT subgroup (p = 0.018). However, there was no statistically significant difference in Constant score and DASH score while comparing the CT subgroup to other subgroups. Although TEN fixation may lead to a higher degree of length shortening after bony union especially in cases of comminuted fracture pattern, no statistically significant difference was observed in objective functional results as compared to other subgroups. Therefore, TEN can be used to fix a displaced midshaft clavicle fracture even in cases of comminuted fracture pattern, which overall is an effective and less surgically invasive procedure. PMID- 26362961 TI - What is harmful for male fertility: cell phone or the wireless Internet? AB - In this study, we aimed to assess the potential harmful effects of radiofrequency electromagnetic radiation on sperm parameters. We requested semen for analyses from the male patients coming to our infertility division and also asked them to fill out an anonymous questionnaire. We queried their mobile phone and wireless Internet usage frequencies in order to determine their radiofrequency electromagnetic radiation exposure. A total of 1082 patients filled the questionnaire but 51 of them were excluded from the study because of azoospermia. There was no significant difference between sperm counts and sperm morphology excluding sperm motility, due to mobile phone usage period, (p = 0.074, p = 0.909, and p = 0.05, respectively). The total motile sperm count and the progressive motile sperm count decreased due to the increase of internet usage (p = 0.032 and p = 0.033, respectively). In line with the total motile sperm count, progressive motile sperm count also decreased with wireless Internet usage compared with the wired Internet connection usage (p = 0.009 and p = 0.018, respectively). There was a negative correlation between wireless Internet usage duration and the total sperm count (r = -0.089, p = 0.039). We have also explored the negative effect of wireless Internet use on sperm motility according to our preliminary results. PMID- 26362963 TI - Challenges in the diagnosis of renal tuberculosis. PMID- 26362962 TI - Stress, needs, and quality of life of people living with human immunodeficiency virus/AIDS in Taiwan. AB - Human immunodeficiency virus (HIV)/AIDS is a manageable infectious disease by the effectiveness of highly active antiretroviral therapy. AIDS-related stigma and conflict may create distress and deteriorate quality of life (QoL) of people living with HIV/AIDS (PLWHA). This cross-sectional, descriptive, correlational study using structural questionnaires aimed to explore the stress, needs, QoL, and associated factors of PLWHA in Taiwan. A total of 200 PLWHA participating in this study needed most on treatment of HIV and prevention of AIDS, and health maintenance. They had worse QoL in physical, psychological, and social domains (all p < 0.001) than the general population. Stress was the most significant predictor (beta = -0.25 to -0.54, p < 0.01) for all four domains of QoL. Needs was not significantly associated with QoL. The QoL of PLWHA can be explained by demographics, self-perception on health, needs, and stress for 25.3-40.7% of variances. No association existed between CD4(+) counts and QoL in Taiwanese PLWHA. It is important to recognize the perception of PLWHA on their health status, which is significantly associated with their QoL, besides monitoring their physical indicators of health (CD4(+) counts). To recognize the stress and needs that PLWHA experience and to develop intervention programs targeting strategies on HIV disclosure, prevention and health maintenance are crucial for PLWHA's QoL. PMID- 26362964 TI - Reply: Challenges in the diagnosis of renal tuberculosis. PMID- 26362965 TI - Laparoscopic approach is the treatment of choice for sclerosing angiomatoid nodular transformation of the spleen. PMID- 26362966 TI - Long-term outcomes and predictors in pediatric liver retransplantation. AB - Historically, 9-29% of pediatric liver transplant recipients have required retransplantation. Although outcomes have improved over the last decade, currently published patient and graft survival remain lower after retransplant than after primary transplant. Data from liver retransplantation recipients at our institution between 1991 and 2013 were retrospectively reviewed. Kaplan-Meier estimates were used to depict patient and graft survival. Predictors of survival were analyzed using a series of Cox proportional hazards models. Predictors were analyzed separately for patients who had "early" (<= 30 days after primary transplant) and "late" retransplants. Eighty-four patients underwent retransplant at a median time of 241 days. Sixty percent had late retransplants. At one, five, and 10 yr, actuarial patient and graft survival were 73%/71%, 66%/63%, and 58%/53%, respectively. Since 2002, patient and graft survival improved to 86%/86% at one yr and 93%/87% at five yr. While operative complications were a common cause of death after earlier retransplants, since 2002, infection has been the only cause of death. Significant morbidities at five-yr follow-up include renal dysfunction (15%), diabetes (13%), hypertension (26%), chronic rejection (7%), and PTLD (2%). Current survival after pediatric liver retransplantation has improved significantly, but long-term immunosuppressant morbidity remains an opportunity for improvement. PMID- 26362967 TI - Trajectory Auto-Corrected image reconstruction. AB - PURPOSE: To estimate k-space trajectory errors in non-Cartesian acquisitions and reconstruct distortion-free images, without trajectory measurements or gradient calibrations. THEORY AND METHODS: The Trajectory Auto-Corrected image Reconstruction method jointly estimates k-space trajectory errors and images, based on SENSE and SPIRiT parallel imaging reconstruction. The underlying idea is that parallel imaging and oversampling in the center of k-space provides data redundancy that can be exploited to simultaneously reconstruct images and correct trajectory errors. Trajectory errors are represented as weighted sums of trajectory-dependent error basis functions, the coefficients of which are estimated using gradient-based optimization. RESULTS: Trajectory Auto-Corrected image Reconstruction was applied to reconstruct images and errors in golden angle radial, center-out radial, and spiral in vivo 7 Tesla brain acquisitions in five subjects. Compared to reconstructions using nominal trajectories, Trajectory auto corrected image reconstructions contained considerably less blurring and streaking and were of similar quality to images reconstructed using measured k space trajectories in the center-out radial and spiral cases. Reconstruction cost function reductions and improvements in normalized image gradient squared were also similar to those for images reconstructed using measured trajectories. CONCLUSION: Trajectory Auto-Corrected image Reconstruction enables non-Cartesian image reconstructions free from trajectory errors without the need for separate gradient calibrations or trajectory measurements. Magn Reson Med 76:757-768, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26362968 TI - Bone reconstruction after surgical treatment of experimental peri-implantitis defects at a sandblasted/acid-etched hydroxyapatite-coated implant: an experimental study in the dog. AB - OBJECTIVES: The objective of this study was to evaluate bone formation/osseointegration following surgical treatment of experimental peri implantitis at dental implants with different surface characteristics exposed to ligature-induced breakdown conditions. METHODS: Ten turned (control), 10 sandblasted/acid-etched (SA), and 10 SA/hydroxyapatite nanocoated (HA) implants were installed into the edentulated posterior mandible in five Beagle dogs and allowed to osseointegrate for 12 weeks. Ligature-induced breakdown defects were then induced over 23 weeks using stainless steel wire ligatures. The ligatures were removed and soft tissues were allowed to heal for 3 weeks. Next, exposed implant surfaces were decontaminated followed by guided bone regeneration using a collagen membrane and submerged wound healing. The animals were euthanized for histometric analysis at 12 weeks post-surgery. RESULTS: The radiographic analysis showed vertical bone loss following ligature-induced breakdown without statistically significant differences among implant technologies. The histometric analysis showed significantly enhanced bone formation (height) at SA and SA/HA compared with turned implants (p = 0.028) following reconstructive surgery. Bone formation area was greater at SA/HA compared with turned implants, however the difference did not reach statistical significance. CONCLUSIONS: While ligature induced defect progression does not appear implant surface dependent in this animal model, bone formation at the decontaminated implant surfaces appears more favourable at SA and SA/HA over turned implants following reconstructive surgery. PMID- 26362969 TI - Ex vivo relaxations of pulmonary arteries induced by prostacyclin mimetics are highly dependent of the precontractile agents. AB - Prostacyclin (PGI2) mimetics (iloprost, treprostinil) are potent vasodilators (primarily via IP-receptor activation) and major therapeutic interventions for pulmonary hypertension (PH). Increased plasma levels of endothelin (ET-1), thromboxane (TxA2) and catecholamines have been demonstrated from patients with PH. In this study, we aimed to compare relaxant effects of iloprost and treprostinil on human (HPA) and rat pulmonary arteries precontracted with either ET-1, thromboxane (U46619) or an alpha-adrenergic receptor agonist (Norepinephrine, NE or phenylephrine, PE). Treprostinil and iloprost induced vasorelaxation of HPA precontracted with NE, ET-1 or U46619. We obtained greater relaxation response and sensitivity to treprostinil when ET-1 or U46619 were used to induce the precontraction in comparison to NE. In contrast, iloprost showed less relaxation response and sensitivity in HPA precontracted with U46619 versus NE. In the rat, treprostinil and iloprost induced vasorelaxation of pulmonary arteries precontracted with PE and U46619 but minimally with ET-1. However, in rat pulmonary arteries, PE-induced precontractions were comparatively low amplitude. Our study showed that the ex vivo relaxation or sensitivity of pulmonary arteries induced by PGI2 mimetics is highly dependent on both the pre contraction agent and the species. To best extrapolate to effects on human tissue, our results suggest that U46619 is the appropriate contractile agent for assessing the relaxant effect of PGI2 mimetics in rat pulmonary arteries. Finally we suggest that in PH patients with high plasma concentration of TxA2, treprostinil (not iloprost) would be a preferential treatment. On the other hand, if the ET-1 plasmatic level is high, either treprostinil or iloprost will be effective. PMID- 26362970 TI - [Idiopathic Nephrotic Syndrome: recommendations of the Nephrology Branch of the Chilean Society of Pediatrics. Part One]. AB - Idiopathic nephrotic syndrome is the most common glomerular disease in childhood, affecting 1 to 3 per 100,000 children under the age of 16. It most commonly occurs in ages between 2 and 10. Its cause is unknown and its histology corresponds to minimal change disease in 90% of cases, or focal segmental glomerulosclerosis. 80 to 90% of cases respond to steroids (steroid-sensitive nephrotic syndrome) with good prognosis and long-term preservation of renal function over time. 70% of patients with SSNS have one or more relapses in their evolution, and of these, 50% behave as frequent relapsing or steroid-dependent, a group that concentrate the risk of steroid toxicity. Patients with steroid resistant nephrotic syndrome have a poor prognosis and 50% of them evolve to end stage renal disease. The goal of therapy is to induce and maintain remission of the disease, reducing the risk secondary to proteinuria while minimizing the adverse effects of treatments, especially with prolonged use of corticosteroids. This paper is the result of the collaborative effort of the Nephrology Branch of the Chilean Society of Pediatrics with aims at helping pediatricians and pediatric nephrologists to treat pediatric SNI. In this first part, recommendations of steroid-sensitive nephrotic syndrome are discussed. PMID- 26362971 TI - Reduced protein availability by albumen removal during chicken embryogenesis decreases body weight and induces hormonal changes. AB - NEW FINDINGS: What is the central question of this study? Prenatal protein undernutrition by albumen removal in an avian model of fetal programming leads to long-term programming effects, but when do these effects first appear and are these programming effects regulated by the same candidate genes as in mammals? What is the main finding and its importance? The present results indicate that prenatal protein undernutrition by albumen removal induces phenotypical and hormonal changes in the early posthatch period, when the mismatch between the prenatal and postnatal environment first arises, but these changes are not accompanied by an altered gene expression of the selected candidate genes. Studies of the chicken offer a unique model for investigation of the direct effects of reduced prenatal protein availability by the partial replacement of albumen with saline in eggs at embryonic day 1 (albumen-deprived group). The results were compared with mock-treated sham chicks and non-treated control chicks. Although no differences in hatch weight were found, body weight and growth were reduced in the albumen-deprived chicks until 3 weeks of age. The feed intake of the albumen-deprived chicks, however, was increased compared with the control (day 13-21) and the sham chicks (day 16-18). In the albumen-deprived chicks, the ratio of thyroxine to 3,5,3'-triiodothyronine in the plasma was increased compared with the control chicks, whereas the plasma corticosterone level was increased only at day 7 compared with both other groups. The plasma glucose concentration and glucose tolerance were not affected by treatment. Several candidate genes previously associated with effects of prenatal protein deprivation in mammals were examined in the liver of newly hatched chicks. Gene expression of glycogen synthase 2, glycogen phosphorylase 1, peroxisome proliferator-activated receptor alpha and gamma and glucocorticoid receptor was not affected by the treatment. In conclusion, reduction of prenatal protein availability led to differences in body weight and influenced hormones involved in metabolism and growth. Gene expression of the selected candidate genes was not altered, in contrast to mammals. PMID- 26362972 TI - Contributions of cerebellar event-based temporal processing and preparatory function to speech perception. AB - The role of the cerebellum in the anatomical and functional architecture of the brain is a matter of ongoing debate. We propose that cerebellar temporal processing contributes to speech perception on a number of accounts: temporally precise cerebellar encoding and rapid transmission of an event-based representation of the temporal structure of the speech signal serves to prepare areas in the cerebral cortex for the subsequent perceptual integration of sensory information. As speech dynamically evolves in time this fundamental preparatory function may extend its scope to the predictive allocation of attention in time and supports the fine-tuning of temporally specific models of the environment. In this framework, an oscillatory account considering a range of frequencies may best serve the linking of the temporal and speech processing systems. Lastly, the concerted action of these processes may not only advance predictive adaptation to basic auditory dynamics but optimize the perceptual integration of speech. PMID- 26362973 TI - Interaction between fat type and lysolecithin supplementation in broiler feeds. AB - Lysolecithins are added to poultry diets to promote the intestinal absorption of nutrients, in particular of dietary fats. Lysolecithins contain a mixture of phospho- and lysophospholipids and differ in composition depending on the conditions and source of the lecithin used for its production. The importance of the lysolecithin composition and its interaction with the fat type was investigated in vitro in a fat digestion model and in vivo in a digestibility trial with broilers (24 to 28 d age). The in vitro digestion of soybean oil and pig lard was investigated without and with the inclusion of soybean or rapeseed lysolecithin. Correspondingly, for the digestibility trial, 108 Ross 308 male broilers were assigned to 6 dietary treatments: a basal diet with either soybean oil (5.3%) or pig lard (5.8%), each basal diet supplemented with 250 ppm soybean lysolecithin, and each basal diet supplemented with 250 ppm rapeseed lysolecithin. In vitro pig lard digestibility was significantly lower compared to soybean oil digestibility. Although in vivo no significant difference was observed for crude fat digestibility, broilers fed the basal diet with pig lard had a lower (P < 0.05) DM digestibility, nitrogen retention, and AMEn compared to those fed the basal diet with soybean oil. Lysolecithin supplementation showed a significant interaction with the fat type, both in vitro and in vivo. The in vitro hydrolysis of pig lard, but not of soybean oil, increased (P < 0.001) with supplementation of soybean and rapeseed lysolecithin. Moreover, soybean and rapeseed lysolecithin supplementation improved (P < 0.05) DM digestibility of the basal diet with pig lard by 5.1 and 5.7%, respectively; nitrogen retention by 2.8 and 3.1 g/kg, respectively; and AMEn by 182 and 199 kcal/kg, respectively. Despite the major difference in molecular composition, there was, however, no impact of the lysolecithin composition on in vitro and in vivo fat digestibility. This study demonstrates that the improvements that can be made with lysolecithin supplementation are highly dependent on the fat incorporated in broiler feeds. PMID- 26362974 TI - Effects of heat stress on peripheral T and B lymphocyte profiles and IgG and IgM serum levels in broiler chickens vaccinated for Newcastle disease virus. AB - Multiple factors, such as environment, nutritional status, and disease, induce stress in animals during livestock production. It has been shown that poultry exposed to stressors for prolonged periods had decreases in their performance parameters, mortality and decreased host resistance to pathogenic agents. It seems that early age stress may have long-lasting impact and could possibly modify the expression of their genetic potential on growth performance and immunity. This study aimed to discuss the effects of early-age heat stress on the blood lymphocyte phenotypes (B and T lymphocytes) and plasma immunoglobulin levels (IgM and IgG) in chickens vaccinated against paramixovirus of the Newcastle (NC) disease (LaSota strain). For this purpose, 96 male chickens (Cobb) were divided into 4 groups: 1) control (C), 2) heat-stressed (HS), 3) control vaccinated (C/V), and 4) heat-stressed and Vaccinated (HS/V). The NC vaccine was administered twice on experimental day (ED) 7 and ED14, and the heat stress (38 +/- 1 degrees C) was applied from ED2 to ED6. The data showed that HS increased the corticosterone serum levels in the HS group compared with the control groups (C and C/V groups). At ED7, increased concentrations of IgM were observed in birds in the HS and HS/V groups compared with C and C/V animals; chickens from the HS/V group presented increased IgG levels compared with those in the birds of the C group. The heat stress shifted the immune cell profile from B-lymphocyte to a T-cytotoxic and T-helper lymphocyte profile, and this immune cell pattern persisted until the end of the study period. It was concluded that heat stress immunomodulated the immune function response of the chickens to the NC disease vaccine challenge. PMID- 26362975 TI - Effects of flavones of sea buckthorn fruits on growth performance, carcass quality, fat deposition and lipometabolism for broilers. AB - The objective of this study was to evaluate the effects of different levels of flavones of sea buckthorn fruits (FSBF) on growth performance, carcass quality, fat deposition, and lipometabolism for broilers. 240 one-day-old Arbor Acres male broilers were randomly allotted to 4 dietary treatments (0, 0.05%, 0.10%, and 0.15% FSBF) with 6 replicates of 10 birds. Broilers were reared for 42 d. Results showed FSBF quadratically improved average daily feed intake (ADFI), average daily gain (ADG), and final body weight (BW) (P = 0.002, P = 0.019 and P = 0.018, respectively). The abdominal fat percentage in 0.05%, 0.10%, and 0.15% FSBF supplementation groups was decreased by 21.08%, 19.12%, and 19.61% with respect to the control group, respectively (P < 0.05). The intramuscular fat (IMF) content in the breast muscle of the broilers was increased by 7.21%, 23.42% and 6.30% in 0.05%, 0.10% and 0.15% FSBF groups, and that in the thigh meat was raised by 4.43%, 24.63% and 12.32%, compared with the control group, respectively (P < 0.05). FSBF had a quadratic effect on the abdominal fat percentage and IMF in the breast muscle (P < 0.05). Dietary FSBF also modified fatty acids of muscular tissues, resulting in a higher ratio of unsaturated to saturated fatty acids (P < 0.05). Supplementing FSBF in the diet greatly decreased the levels of triglyceride, cholesterol, and low-density lipoprotein cholesterol (P < 0.05). Moreover, the quadratic responses were also observed in the levels of insulin and adiponectin in serum (P = 0.020 and P = 0.037, respectively). Abdominal fat percentage was correlated negatively with insulin and positively with adiponectin (P < 0.05). IMF content in the breast and thigh muscles were correlated positively with insulin, and negatively with adiponectin (P < 0.05). A positive correlation existed between breast muscle, IMF, and leptin (P < 0.05). In conclusion, adding FSBF into the diets affected growth performance and fat deposition of broilers by regulating lipometabolism. Fat deposition and distribution of broilers were closely associated with concentrations of insulin and adiponectin. The optimal level of FSBF supplemented in diet was 0.05 to 0.10% in this study. PMID- 26362976 TI - Are parent-reared red-legged partridges (Alectoris rufa) better candidates for re establishment purposes? AB - Aiming to produce game birds suitable for re-establishment purposes, we studied the survival and behavior of 31 adult red-legged partridges reared by their natural parents in captivity (parent-reared) and 67 wild red-legs (35 adults and 32 subadults). Birds were radio-tracked and released in a game estate where management targeting small game species was conducted and shooting was not allowed. Survival of parent-reared partridges was shorter (mean 108 d) than wild adults (mean 160 d), though no significant differences were found. Parent-reared birds showed a longer escape reaction (mean 11.7 sec) than wild adults (mean 0.4 sec) and were mainly predated by terrestrial predators (52%), whereas the most important source of predation in wild red-legs was raptors (49%). The home range of parent-reared (mean 23 ha) was not significantly lower than wild adults (mean 27 ha). Nineteen percent of parent-reared and 31.4% of wild adults paired successfully, and we recorded 6 pairs in which one bird was wild and the other parent-reared and one pair in which both birds were parent-reared. A small proportion of red-legs started incubation (parent-reared 12.9%, wild 20%), and the proportion completing incubation was similar among wild and parent-reared birds. Overall, parent-reared red-legs showed similar survival and behavior compared to wild red-legs and better than intensively reared, so parent-reared red-legs should be chosen for the re-establishment of wild populations. PMID- 26362977 TI - Influence of the main cereal and feed form of the rearing phase diets on performance, digestive tract, and body traits of brown-egg laying pullets from hatch to 17 weeks of age. AB - The effects of the main cereal and feed form of the rearing phase diets on growth performance, gastrointestinal tract characteristics, and body traits were studied in brown-egg pullets from hatch to 17 wk of age. Eight dietary treatments that were a combination of 2 main cereals (corn vs. wheat) and 4 feeding programs were used. The feeding program consisted in feeding crumbles from 0 to 5, 0 to 10, or 0 to 17 wk of age followed by mash until 17 wk, or feeding mash continuously from 0 to 17 wk. Each treatment was replicated 9 times. From hatch to 17 wk of age, pullets fed corn had similar ADG but poorer feed conversion ratio (FCR; P < 0.001) than pullets fed wheat. Also, pullets fed crumbles continuously (0 to 17 wk) had greater ADG (12.3 vs. 11.5 g; P < 0.001) and better FCR (4.21 vs. 4.36; P < 0.001) than pullets feed mash continuously, with pullets that were changed at any age of the rearing period from crumbles to mash feeding showing intermediate results. At 17 wk of age, the relative weights (% BW) of the gastrointestinal tract and gizzard were greater in pullets fed corn than in pullets fed wheat (P < 0.01) but the relative length (cm/kg full BW) of the small intestine, body, and tarsus was not affected. Pullets fed crumbles continuously had lighter gizzards (P < 0.001), higher gizzard pH (P < 0.001), and were shorter (P < 0.01) than pullets fed mash continuously, with pullets fed the other 2 treatments being intermediate. In summary, wheat can be used in substitution of corn in pullet diets without any adverse effect on growth performance. Feeding crumbles improves pullet performance but hinders gizzard and gastrointestinal tract development. Growth performance, gastrointestinal tract, and body traits of the pullets re adapt quickly to changes in feed form of the rearing diets. PMID- 26362978 TI - Effect of plant extracts derived from thyme on male broiler performance. AB - The effect of dietary thyme-oil extract (TOE) supplementation on immune functions of broilers were assessed by feeding graded levels (50, 100, 200, or 400 ppm) of TOE to male broiler chicks during a 42-d feeding trial compared with negative- or positive-control diets. Dietary control treatments included a negative-control diet with no feed-additive supplementation and 2 positive-control groups supplemented with either virginiamycin or zinc bacitracin. In total, 300 1-day old Ross * Ross male broilers were randomly assigned to 6 dietary treatments that consisted of 5 replicates of 10 birds each. On d 21 and 42, 2 birds from each replicate were killed by cervical cutting to measure the relative weights of spleen and bursa of Fabricius. At 25 d of age, chicks were injected with 0.5 mL of 10% SRBC suspension. Broilers fed with 200 ppm of TOE had heavier weights of bursa of Fabricius than those fed other dietary treatments at d 42 of age. Furthermore, dietary inclusion of 100 ppm of TOE resulted in higher (P < 0.05) total immunoglobulin response in primary antibody titer against sheep erythrocytes compared with other dietary treatments. On the other hand, diet modifications had no significant effect on blood leukocyte subpopulations and heterophil-to-lymphocyte ratio. These results suggest that dietary supplementation with TOE, especially at the level of 100 ppm, can improve immunological responses of broiler chicks. PMID- 26362979 TI - Manipulation of broiler chickens sex differentiation by in ovo injection of aromatase inhibitors, and garlic and tomato extracts. AB - The influence of in ovo administration of aromatase inhibitors, clomiphen citrate, tomoxifen, and garlic and tomato extracts on sex differentiation in broiler chickens were investigated in 2 experiments. Five hundred, and 1,000 fertile eggs from Ross 308 strain were used in experiments 1 and 2, respectively. In both experiments, eggs were divided into 5 groups: control group (DW, 0.1 mL/egg), tomoxifen (0.05 mg/egg), clomiphene citrate (0.05 mg/egg), garlic and tomato extracts (0.1 mL/egg). Eggs were sanitized and prepared for incubation in a regular automatic hatchery. Experimental preparations were injected into eggs at day 5 of the incubation period. Injection sites on the eggs were cleaned with 70% ethylic alcohol, bored by a needle, and aromatase inhibitors were injected into the white from the thin end of the eggs by insulin syringe and then sealed by melted paraffin. In experiment 1, hatched one-day-old chicks (mixed-sex) were raised till 42 days of age in 25 floor pens with a completely randomized design. Experiment 2 was designed to investigate the effects of sex and treatments on the feed-to-gain ratio of broiler chicks. In experiment 2, hatched one-day-old chicks were feather sexed and raised till 42 days of age in 50 floor pens. A completely randomized design with a 2 * 5 factorial arrangement of treatments (sex*treatment) was used. Gonads of the chicks were checked to determine their sex on day 42 by optic microscope to make sure feather sexing was correct. At the end of both experiments, on day 42, one bird from each pen was slaughtered for carcass analysis. In experiment 1, hatchability and the one-day-old weight of chicks showed no significant differences among treatments (P > 0.05). However, in ovo administration of garlic and tomato extracts caused the highest percentage of male chicks (P < 0.05). Also, the percentage of thighs and wings of the males were significantly higher than those of females (P < 0.05). In experiment 2, feed to-gain ratio of male and female broiler chicks showed no significant differences among treatments (P > 0.05). PMID- 26362980 TI - Halobacillus sediminis sp. nov., a moderately halophilic bacterium isolated from a solar saltern sediment. AB - A Gram-staining-positive, moderately halophilic bacterium, designated strain NGS 2T, was isolated from sediment of a solar saltern pond located in Shinan, Korea. Strain NGS-2T was a strictly aerobic, non-motile rod that grew at pH 5.0-10.0 (optimum, pH 8.0), at 10-30 degrees C (optimum, 28 degrees C) and in the presence of 1-20 % (w/v) NaCl (optimum, 10 % NaCl). Phylogenetic analyses based on 16S rRNA gene sequences indicated that strain NGS-2T belonged to the genus Halobacillus, with sequence similarity of 98.4-95.8 % to existing type strains, showing the highest sequence similarity to Halobacillus dabanensis D-8T (98.4 %), H. litoralis SL-4T (98.4 %), H. trueperi SL-5T (98.2 %), H. faecis IGA7-4T (98.2 %), H. profundi IS-Hb4T (98.1 %) and H. mangrovi MS10T (98.0 %). The major polar lipids were phosphatidylglycerol, phosphatidylethanolamine, phosphatidyl-N methylethanolamine and an unknown glycolipid. The cell-wall peptidoglycan was based on l-Orn-d-Asp, the predominant isoprenoid quinone was menaquinone 7 (MK-7) and the major fatty acids were anteiso-C15: 0 and anteiso-C17: 0. The DNA G+C content of the novel isolate was 45.0 mol%. Levels of DNA-DNA relatedness between strain NGS-2T and the type strains of 12 other species of the genus ranged from 32 to 3 %. On the basis of the polyphasic analysis conducted in this study, strain NGS-2T represents a novel species of the genus Halobacillus, for which the name Halobacillus sediminis sp. nov. is proposed. The type strain is NGS-2T ( = KACC 18263T = NBRC 110639T). PMID- 26362981 TI - A single mutation in the gene responsible for the mucoid phenotype of Bifidobacterium animalis subsp. lactis confers surface and functional characteristics. AB - Exopolysaccharides (EPS) are extracellular carbohydrate polymers synthesized by a large variety of bacteria. Their physiological functions have been extensively studied, but many of their roles have not yet been elucidated. We have sequenced the genomes of two isogenic strains of Bifidobacterium animalis subsp. lactis that differ in their EPS-producing phenotype. The original strain displays a nonmucoid appearance, and the mutant derived thereof has acquired a mucoid phenotype. The sequence analysis of their genomes revealed a nonsynonymous mutation in the gene Balat_1410, putatively involved in the elongation of the EPS chain. By comparing a strain from which this gene had been deleted with strains containing the wild-type and mutated genes, we were able to show that each strain displays different cell surface characteristics. The mucoid EPS synthesized by the strain harboring the mutation in Balat_1410 provided higher resistance to gastrointestinal conditions and increased the capability for adhesion to human enterocytes. In addition, the cytokine profiles of human peripheral blood mononuclear cells and ex vivo colon tissues suggest that the mucoid strain could have higher anti-inflammatory activity. Our findings provide relevant data on the function of Balat_1410 and reveal that the mucoid phenotype is able to alter some of the most relevant functional properties of the cells. PMID- 26362982 TI - Meta-analysis of the effects of sanitizing treatments on Salmonella, Escherichia coli O157:H7, and Listeria monocytogenes inactivation in fresh produce. AB - The aim of this study was to perform a meta-analysis of the effects of sanitizing treatments of fresh produce on Salmonella spp., Escherichia coli O157:H7, and Listeria monocytogenes. From 55 primary studies found to report on such effects, 40 were selected based on specific criteria, leading to more than 1,000 data on mean log reductions of these three bacterial pathogens impairing the safety of fresh produce. Data were partitioned to build three meta-analytical models that could allow the assessment of differences in mean log reductions among pathogens, fresh produce, and sanitizers. Moderating variables assessed in the meta analytical models included type of fresh produce, type of sanitizer, concentration, and treatment time and temperature. Further, a proposal was done to classify the sanitizers according to bactericidal efficacy by means of a meta analytical dendrogram. The results indicated that both time and temperature significantly affected the mean log reductions of the sanitizing treatment (P < 0.0001). In general, sanitizer treatments led to lower mean log reductions when applied to leafy greens (for example, 0.68 log reductions [0.00 to 1.37] achieved in lettuce) compared to other, nonleafy vegetables (for example, 3.04 mean log reductions [2.32 to 3.76] obtained for carrots). Among the pathogens, E. coli O157:H7 was more resistant to ozone (1.6 mean log reductions), while L. monocytogenes and Salmonella presented high resistance to organic acids, such as citric acid, acetic acid, and lactic acid (~3.0 mean log reductions). With regard to the sanitizers, it has been found that slightly acidic electrolyzed water, acidified sodium chlorite, and the gaseous chlorine dioxide clustered together, indicating that they possessed the strongest bactericidal effect. The results reported seem to be an important achievement for advancing the global understanding of the effectiveness of sanitizers for microbial safety of fresh produce. PMID- 26362983 TI - High prevalence and genetic heterogeneity of rodent-borne Bartonella species on Heixiazi Island, China. AB - We performed genetic analysis of Bartonella isolates from rodent populations from Heixiazi Island in northeast China. Animals were captured at four sites representing grassland and brushwood habitats in 2011 and examined for the prevalence and genetic diversity of Bartonella species, their relationship to their hosts, and geographic distribution. A high prevalence (57.7%) and a high diversity (14 unique genotypes which belonged to 8 clades) of Bartonella spp. were detected from 71 rodents comprising 5 species and 4 genera from 3 rodent families. Forty-one Bartonella isolates were recovered and identified, including B. taylorii, B. japonica, B. coopersplainsensis, B. grahamii, B. washoensis subsp. cynomysii, B. doshiae, and two novel Bartonella species, by sequencing of four genes (gltA, the 16S rRNA gene, ftsZ, and rpoB). The isolates of B. taylorii and B. grahamii were the most prevalent and exhibited genetic difference from isolates identified elsewhere. Several isolates clustered with strains from Japan and far-eastern Russia; strains isolated from the same host typically were found within the same cluster. Species descriptions are provided for Bartonella heixiaziensis sp. nov. and B. fuyuanensis sp. nov. PMID- 26362984 TI - Metabolic engineering of a novel muconic acid biosynthesis pathway via 4 hydroxybenzoic acid in Escherichia coli. AB - cis,cis-Muconic acid (MA) is a commercially important raw material used in pharmaceuticals, functional resins, and agrochemicals. MA is also a potential platform chemical for the production of adipic acid (AA), terephthalic acid, caprolactam, and 1,6-hexanediol. A strain of Escherichia coli K-12, BW25113, was genetically modified, and a novel nonnative metabolic pathway was introduced for the synthesis of MA from glucose. The proposed pathway converted chorismate from the aromatic amino acid pathway to MA via 4-hydroxybenzoic acid (PHB). Three nonnative genes, pobA, aroY, and catA, coding for 4-hydroxybenzoate hydrolyase, protocatechuate decarboxylase, and catechol 1,2-dioxygenase, respectively, were functionally expressed in E. coli to establish the MA biosynthetic pathway. E. coli native genes ubiC, aroF(FBR), aroE, and aroL were overexpressed and the genes ptsH, ptsI, crr, and pykF were deleted from the E. coli genome in order to increase the precursors of the proposed MA pathway. The final engineered E. coli strain produced nearly 170 mg/liter of MA from simple carbon sources in shake flask experiments. The proposed pathway was proved to be functionally active, and the strategy can be used for future metabolic engineering efforts for production of MA from renewable sugars. PMID- 26362985 TI - Membrane-associated glucose-methanol-choline oxidoreductase family enzymes PhcC and PhcD are essential for enantioselective catabolism of dehydrodiconiferyl alcohol. AB - Sphingobium sp. strain SYK-6 is able to degrade various lignin-derived biaryls, including a phenylcoumaran-type compound, dehydrodiconiferyl alcohol (DCA). In SYK-6 cells, the alcohol group of the B-ring side chain of DCA is initially oxidized to the carboxyl group to generate 3-(2-(4-hydroxy-3-methoxyphenyl)-3 (hydroxymethyl)-7-methoxy-2,3-dihydrobenzofuran-5-yl) acrylic acid (DCA-C). Next, the alcohol group of the A-ring side chain of DCA-C is oxidized to the carboxyl group, and then the resulting metabolite is catabolized through vanillin and 5 formylferulate. In this study, the genes involved in the conversion of DCA-C were identified and characterized. The DCA-C oxidation activities in SYK-6 were enhanced in the presence of flavin adenine dinucleotide and an artificial electron acceptor and were induced ca. 1.6-fold when the cells were grown with DCA. Based on these observations, SLG_09480 (phcC) and SLG_09500 (phcD), encoding glucose-methanol-choline oxidoreductase family proteins, were presumed to encode DCA-C oxidases. Analyses of phcC and phcD mutants indicated that PhcC and PhcD are essential for the conversion of (+)-DCA-C and (-)-DCA-C, respectively. When phcC and phcD were expressed in SYK-6 and Escherichia coli, the gene products were mainly observed in their membrane fractions. The membrane fractions of E. coli that expressed phcC and phcD catalyzed the specific conversion of DCA-C into the corresponding carboxyl derivatives. In the oxidation of DCA-C, PhcC and PhcD effectively utilized ubiquinone derivatives as electron acceptors. Furthermore, the transcription of a putative cytochrome c gene was significantly induced in SYK-6 grown with DCA. The DCA-C oxidation catalyzed by membrane-associated PhcC and PhcD appears to be coupled to the respiratory chain. PMID- 26362986 TI - Expansion of the tetracycline-dependent regulation toolbox for Helicobacter pylori. AB - In an effort to gain greater understanding of the biology and infection processes of Helicobacter pylori, we have expanded the functionality of the tetracycline dependent gene regulation (tet) system to provide more improved and versatile genetic control and facilitate the generation of conditional mutants to study essential genes. Second-generation tetracycline-responsive H. pylori uPtetO5 promoters were based on the mutated core ureA promoter. Single point mutations at either the ribosomal binding site or the start codon were introduced to shift the regulatory range of three uPtetO5 derivatives. All promoters were tested for regulation by TetR and revTetR using dapD, a gene essential to peptidoglycan biosynthesis, as a reporter. All tet promoters were effectively regulated by both TetR and revTetR, and their regulation windows overlapped so as to cover a broad range of expression levels. tet promoters uPtetO5m1 and uPtetO5m2 could be sufficiently silenced by both TetR and revTetR so that the conditional mutants could not grow in the absence of diaminopimelic acid (DAP). Furthermore, through the use of these inducible promoters, we reveal that insufficient DAP biosynthesis results in viable cells with altered morphology. Overall, the development and optimization of tet regulation for H. pylori will not only permit the study of essential genes but also facilitate investigations into gene dosage effects on H. pylori physiology. PMID- 26362988 TI - Inheritance, Realized Heritability, and Biochemical Mechanisms of Malathion Resistance in Bactrocera dorsalis (Diptera: Tephritidae). AB - To better characterize the resistance development and therefore establish effective pest management strategies, this study was undertaken to investigate the inheritance mode and biochemical mechanisms of malathion resistance in the oriental fruit fly, Bactrocera dorsalis (Hendel), which is one of the most notorious pests in the world. After 22 generations of selection with malathion, the malathion-resistant (MR) strain of B. dorsalis developed a 34-fold resistance compared with a laboratory susceptible strain [malathion-susceptible (MS)]. Bioassay results showed that there was no significant difference between the LD50 values of malathion against the progenies from both reciprocal crosses (F(1)-SR and F(1)-RS). The degree of dominance values (D) was calculated as 0.39 and 0.32 for F(1)-RS and F(1)-SR, respectively. The logarithm dosage-probit mortality lines of the F(2) generation and progeny from the backcross showed no clear plateaus of mortality across a range of doses. In addition, Chi-square analysis revealed significant differences between the mortality data and the theoretical expectations. The realized heritability (h(2)) value was 0.16 in the laboratory selected resistant strain of B. dorsalis. Enzymatic activities identified significant changes of carboxylesterases, cytochrome P450 (general oxidases), and glutathione S-transferases in MR compared with the MS strain of B. dorsalis. Taken together, this study revealed for the first time that malathion resistance in B. dorsalis follows an autosomal, incompletely dominant, and polygenic mode of inheritance and is closely associated with significantly elevated activities of three major detoxification enzymes. PMID- 26362987 TI - Genome-wide RNA sequencing analysis of quorum sensing-controlled regulons in the plant-associated Burkholderia glumae PG1 strain. AB - Burkholderia glumae PG1 is a soil-associated motile plant-pathogenic bacterium possessing a cell density-dependent regulation system called quorum sensing (QS). Its genome contains three genes, here designated bgaI1 to bgaI3, encoding distinct autoinducer-1 (AI-1) synthases, which are capable of synthesizing QS signaling molecules. Here, we report on the construction of B. glumae PG1 DeltabgaI1, DeltabgaI2, and DeltabgaI3 mutants, their phenotypic characterization, and genome-wide transcriptome analysis using RNA sequencing (RNA-seq) technology. Knockout of each of these bgaI genes resulted in strongly decreased motility, reduced extracellular lipase activity, a reduced ability to cause plant tissue maceration, and decreased pathogenicity. RNA-seq analysis of all three B. glumae PG1 AI-1 synthase mutants performed in the transition from exponential to stationary growth phase revealed differential expression of a significant number of predicted genes. In comparison with the levels of gene expression by wild-type strain B. glumae PG1, 481 genes were differentially expressed in the DeltabgaI1 mutant, 213 were differentially expressed in the DeltabgaI2 mutant, and 367 were differentially expressed in the DeltabgaI3 mutant. Interestingly, only a minor set of 78 genes was coregulated in all three mutants. The majority of the QS-regulated genes were linked to metabolic activities, and the most pronounced regulation was observed for genes involved in rhamnolipid and Flp pilus biosynthesis and the type VI secretion system and genes linked to a clustered regularly interspaced short palindromic repeat (CRISPR)-cas gene cluster. PMID- 26362989 TI - Early Detection and Mitigation of Resistance to Bt Maize by Western Corn Rootworm (Coleoptera: Chrysomelidae). AB - Transgenic Bt maize that produces less than a high-dose has been widely adopted and presents considerable insect resistance management (IRM) challenges. Western corn rootworm, Diabrotica virgifera virgifera LeConte, has rapidly evolved resistance to Bt maize in the field, leading to local loss of efficacy for some corn rootworm Bt maize events. Documenting and responding to this resistance has been complicated by a lack of rapid diagnostic bioassays and by regulatory triggers that hinder timely and effective management responses. These failures are of great concern to the scientific and agricultural community. Specific challenges posed by western corn rootworm resistance to Bt maize, and more general concerns around Bt crops that produce less than a high-dose of Bt toxin, have caused uncertainty around current IRM protocols. More than 15 years of experience with IRM has shown that high-dose and refuge-based IRM is not applicable to Bt crops that produce less than a high-dose. Adaptive IRM approaches and pro-active, integrated IRM-pest management strategies are needed and should be in place before release of new technologies that produce less than a high-dose. We suggest changes in IRM strategies to preserve the utility of corn rootworm Bt maize by 1) targeting local resistance management earlier in the sequence of responses to resistance and 2) developing area-wide criteria to address widespread economic losses. We also favor consideration of policies and programs to counteract economic forces that are contributing to rapid resistance evolution. PMID- 26362990 TI - Prionic Acid: An Effective Sex Attractant for an Important Pest of Sugarcane, Dorysthenes granulosus (Coleoptera: Cerambycidae: Prioninae). AB - Male Dorysthenes granulosus (Thomson, 1860) (Coleoptera: Cerambycidae: Prioninae) were caught in traps baited with racemic 3,5-dimethyldodecanoic acid (prionic acid) during field screening trials in China that tested known cerambycid pheromones. This species is an important pest of sugarcane (Saccharum officinarum L.). In follow-up dose-response trials, plastic sachets loaded with 1 or 0.1 mg of prionic acid were equally attractive to male beetles, whereas lower doses were no better than controls. Two commercial prionic acid lures also were attractive, suggesting that traps baited with prionic acid can be rapidly incorporated into integrated pest management programs targeting this major pest. It is likely that this compound is a major component of the female-produced sex pheromone of D. granulosus because this species is in the same subfamily as Prionus californicus Motschulsky, 1845, the species from which prionic acid was originally identified. PMID- 26362991 TI - Effects of Methyl Eugenol Feeding on Mating Compatibility of Asian Population of Bactrocera dorsalis (Diptera: Tephritidae) with African Population and with B. carambolae. AB - Males of some species included in the Bactrocera dorsalis complex are strongly attracted to methyl eugenol (ME) (1,2-dimethoxy-4-(2-propenyl) benzene), a natural compound occurring in a variety of plant species. ME feeding of males of the B. dorsalis complex is known to enhance their mating competitiveness. Within B. dorsalis, recent studies show that Asian and African populations of B. dorsalis are sexually compatible, while populations of B. dorsalis and Bactrocera carambolae are relatively incompatible. The objectives of this study were to examine whether ME feeding by males affects mating compatibility between Asian and African populations of B. dorsalis and ME feeding reduces male mating incompatibility between B. dorsalis (Asian population) and B. carambolae. The data confirmed that Asian and African populations of B. dorsalis are sexually compatible for mating and showed that ME feeding only increased the number of matings. Though ME feeding also increased the number of matings of B. dorsalis (Asian population) and B. carambolae males but the sexual incompatibility between both species was not reduced by treatment with ME. These results conform to the efforts resolving the biological species limits among B. dorsalis complex and have implications for fruit fly control programs in fields and horticultural trade. PMID- 26362992 TI - TLR4 Activation Promotes the Secretion of IL-8 Which Enhances the Invasion and Proliferation of Endometrial Stromal Cells in an Autocrine Manner via the FAK Signal Pathway. AB - PROBLEM: Chronic inflammation is important for the occurrence of endometriosis, but the molecular mechanisms are still poorly understood. TLR4 is not only expressed on immune cells but is also present in the human endometrium, and its regulation might be crucial for the pathogenesis of endometriosis. METHOD OF STUDY: In this study, the expression of TLR4 in normal, eutopic endometrium, and ectopic tissues was analyzed by immunohistochemistry. The expression of the key molecules in endometrial stromal cells (ESCs) was assessed by in-cell Western assays. The invasion of eutopic ESCs from patients with endometriosis was evaluated by Matrigel invasion assay. The effects of CXCL8 on the proliferation of ESCs in vitro were assessed using BrdU assays. RESULTS: We found that the expression of TLR4 is higher in the eutopic endometrium than the normal endometrium and that ectopic tissue had the highest level of expression. TLR4 activation stimulated IL-8 secretion and the expression of its receptor CXCR1 in ESCs by activating p38/ERK, but not JNK and NK-kappaB signal pathways. IL-8 could enhance the invasion and proliferation of ESCs through the FAK signal pathway, and these effects could be abolished by an anti-CXCL8 neutralizing antibody or by a FAK inhibitor. PMID- 26362993 TI - Plasticity of crassulacean acid metabolism at subtropical latitudes: a pineapple case study. AB - Plants with the crassulacean acid metabolism (CAM) express high-metabolic plasticity, to adjust to environmental stresses. This article hypothesizes that irradiance and nocturnal temperatures are the major limitations for CAM at higher latitudes such as the Azores (37 degrees 45'N). Circadian CAM expression in Ananas comosus L. Merr. (pineapple) was assessed by the diurnal pattern of leaf carbon fixation into l-malate at the solstices and equinoxes, and confirmed by determining maximal phosphoenolpyruvate carboxylase (PEPC) activity in plant material. Metabolic adjustments to environmental conditions were confirmed by gas exchange measurements, and integrated with environmental data to determine CAM's limiting factors: light and temperature. CAM plasticity was observed at the equinoxes, under similar photoperiods, but different environmental conditions. In spring, CAM expression was similar between vegetative and flowering plants, while in autumn, flowering (before anthesis) and fructifying (with fully developed fruit before ripening) plants accumulated more l-malate. Below 100 umol m(-2) s( 1) , CAM phase I was extended, reducing CAM phase III during the day. Carbon fixation inhibition may occur by two major pathways: nocturnal temperature (<15 degrees C) inhibiting PEPC activity and l-malate accumulation; and low irradiance influencing the interplay between CAM phase I and III, affecting carboxylation and decarboxylation. Both have important consequences for plant development in autumn and winter. Observations were confirmed by flowering time prediction using environmental data, emphasizing that CAM expression had a strong seasonal regulation due to a complex network response to light and temperature, allowing pineapple to survive in environments not suitable for high productivity. PMID- 26362994 TI - Are foods with fat-related claims useful for weight management? AB - Many consumers believe that foods labelled with fat claims (e.g. low fat) are lower in calories than comparable regular foods and are therefore helpful for weight management. However, it is unknown whether such foods are actually lower in calories. Our aims were to determine 1) the relative proportion of foods carrying fat claims among various food categories within the Canadian marketplace; and 2) whether foods with fat claims are actually lower in calories than comparable foods without claims. The Food Label Information Program 2010, a database of Canadian foods developed at the University of Toronto, was used to compare the calorie content of products with and without fat claims within a given food subcategory, as defined by Schedule M of the Food and Drug Regulations. Median differences of 25% or greater were deemed nutritionally significant, as that is the minimum difference required for comparative claims such as "reduced" and "lower" in the Food and Drug Regulations. Fat claims were present on up to 68% of products in a given food subcategory. Products with fat claims were not significantly lower in both fat and calories compared to comparable products without fat claims in more than half of the subcategories (24 out of 40) analyzed. Conversely, in 16 subcategories, foods with fat claims were at least 25% lower in calories; however, for many of these foods, the absolute difference in calories was small, i.e., for 9 of the 16 subcategories, the absolute difference between foods with and without fat claims was <50 calories, even though the relative percent difference was high. This research suggests that foods with fat claims may be misleading consumers and undermining their efforts to manage body weight or prevent obesity. PMID- 26362995 TI - [Pathomimia and plastic surgery, a case report]. AB - Pathomimia is defined as a dummy pathology self-induced deliberately and is neither associated with mental confusion nor disturbance of consciousness. This article reports a case of pathomimia in plastic surgery. One of our patients had intentionally injected physiological saline solution into her breast implants in order to increase their volume. Implants removal was necessary because of severe local inflammatory signs. Psychiatric assessment revealed body dysmorphic disorder (BDD) developed on an hysterical personality, which explained the self induced injuries. This nosologic entity must be promptly identified because it's diagnosis remains problematic and a multidisciplinary medical management is essential. PMID- 26362997 TI - Panobinostat for the Treatment of Multiple Myeloma. AB - Panobinostat is a potent oral deacetylase inhibitor that alters gene expression through epigenetic mechanisms and inhibits protein degradation. It was recently approved by the FDA and EMA for use in combination with bortezomib and dexamethasone in patients with multiple myeloma who have received >=2 prior regimens, including bortezomib and an immunomodulatory drug. Panobinostat was approved based on results from the phase III PANORAMA 1 trial in patients with relapsed or relapsed and refractory multiple myeloma, which showed that panobinostat plus bortezomib and dexamethasone significantly extended progression free survival (median, 12.0 months) compared with placebo plus bortezomib and dexamethasone (median, 8.1 months; P < 0.0001). Additional ongoing trials are evaluating panobinostat in combination with other partners in the relapsed/refractory and newly diagnosed treatment settings. This review focuses on panobinostat and its mechanism of action, pharmacokinetics, and clinical data in the treatment of relapsed or relapsed and refractory multiple myeloma. PMID- 26362996 TI - Molecular Pathways: Targeting ATR in Cancer Therapy. AB - The human ATR gene encodes a kinase that is activated by DNA damage and replication stress as a central transducer of a checkpoint signaling pathway. Once activated, ATR phosphorylates multiple substrates, including the kinase Chk1, to regulate cell-cycle progression, replication fork stability, and DNA repair. These events promote cell survival during replication stress and in cells with DNA damage. Accordingly, there has been the tantalizing possibility that ATR inhibitors would be therapeutically useful, especially if they were more effective in tumor versus normal cells. Indeed, multiple studies have demonstrated that alterations that promote tumorigenesis, such as defects in the ATM-p53 pathway, constitutive oncogene activation, and acquisition of the alternative lengthening of telomeres pathway, render tumor cells sensitive to ATR inhibitor monotherapy and/or increase the synergy between ATR inhibitors and genotoxic chemotherapies. Now, nearly two decades after the discovery of ATR, two highly selective and potent ATR inhibitors, AZD6738 and VX-970, are in early phase clinical trials either as monotherapies or paired with a variety of genotoxic chemotherapies. These trials will generate important insights into the effects of ATR inhibition in humans and the potential role of inhibiting this kinase in the treatment of human malignancies. PMID- 26362998 TI - Seek and Ye Shall Find: Subclonal Anaplastic Lymphoma Kinase Mutations. AB - Bellini and colleagues demonstrate the importance of next-generation sequencing to uncover subclonal anaplastic lymphoma kinase (ALK) mutations in neuroblastoma. Although the significance of these subclonal aberrations is not yet understood, deep sequencing could identify patients whose tumors may respond to ALK inhibitors. PMID- 26363000 TI - Kent GPs commission surgical services from France. PMID- 26362999 TI - From DNA Damage to Nucleic Acid Sensing: A Strategy to Enhance Radiation Therapy. AB - Local irradiation (IR) is widely used in the treatment of primary and metastatic tumors. However, the impact of IR on the immune response is currently being defined. Local and distant relapse after radiotherapy often occurs. The current rationale for the use of IR is based on direct cytotoxicity to cancer cells; however, recent studies have shown that reduction of tumor burden following ablative (large-dose) IR largely depends on type I IFN signaling and CD8(+) T cell response. Here, we review recent findings indicating that antitumor effects of radiation are contributed by both innate and adaptive immune responses. We focus on immune mechanisms, including cytosolic DNA sensing pathways that bridge the traditional view of IR-mediated DNA damage to DNA-sensing immune pathways. Also, we discuss how the efficacy of radiotherapy might be enhanced by targeting nucleic acid-sensing pathways. These findings highlight the mechanisms governing tumor escape from the immune response and the therapeutic potential of synergistic strategies to improve the efficacy of radiotherapy via immunotherapeutic intervention. PMID- 26363001 TI - The effect of the introduction of a nationwide DUR system where local DUR systems are operating--The Korean experience. AB - OBJECTIVE: Outpatient clinics in Korea usually have local DUR (drug utilisation review) systems, which are integrated with EMRs or health insurance claims submission systems. Whenever, the government announces a list of drug contraindications, each local DUR system loads the list and applies it in practice. In December 2010, a nationwide DUR system was introduced. This study is to investigate the impact of the nationwide DUR system on prescribing practices where local DUR systems are already operating. METHODS: Between January 2009 and December 2012 the monthly number of drugs per prescription was retrieved from the health insurance claims data warehouse at the Health Insurance Review and Assessment (HIRA). The monthly proportions of 3 DDI (drug-drug interaction) pairs, 6 drug-age contraindications, and 3 drug-pregnancy contraindications from January 2007 to December 2012, at the outpatient clinic level, were also retrieved. An interrupted time series analysis was used for controlling government announcements of drug contraindications. RESULTS: There was no difference in the number of drugs per prescription before and after the introduction of the nationwide DUR system. Most proportions of the 3 DDI pairs, 6 drug-age contraindications, and 3 drug-pregnancy contraindications, were significantly reduced following the government announcement of drug contraindications in the short term and/or long term. CONCLUSION: The number of drugs per prescription was not related to the nationwide DUR introduction in places where local DUR systems are operating. The introduction of duplicate guidelines, in locations where the guidelines were already well followed, is considered to be the main reason for this. Furthermore, the Doctor's ignorance of alerts, and their continued substitution of regulated drugs, for non-regulated drugs, likely played a role in nullifying the effectiveness of the nationwide DUR system. PMID- 26363002 TI - Radial q-space sampling for DSI. AB - PURPOSE: Diffusion spectrum imaging (DSI) has been shown to be an effective tool for noninvasively depicting the anatomical details of brain microstructure. Existing implementations of DSI sample the diffusion encoding space using a rectangular grid. Here we present a different implementation of DSI whereby a radially symmetric q-space sampling scheme for DSI is used to improve the angular resolution and accuracy of the reconstructed orientation distribution functions. METHODS: Q-space is sampled by acquiring several q-space samples along a number of radial lines. Each of these radial lines in q-space is analytically connected to a value of the orientation distribution functions at the same angular location by the Fourier slice theorem. RESULTS: Computer simulations and in vivo brain results demonstrate that radial diffusion spectrum imaging correctly estimates the orientation distribution functions when moderately high b-values (4000 s/mm2) and number of q-space samples (236) are used. CONCLUSION: The nominal angular resolution of radial diffusion spectrum imaging depends on the number of radial lines used in the sampling scheme, and only weakly on the maximum b-value. In addition, the radial analytical reconstruction reduces truncation artifacts which affect Cartesian reconstructions. Hence, a radial acquisition of q-space can be favorable for DSI. Magn Reson Med 76:769-780, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26363003 TI - Regulation of the human ether-a-go-go-related gene (hERG) potassium channel by Nedd4 family interacting proteins (Ndfips). AB - The cardiac electrical disorder long QT syndrome (LQTS) pre-disposes affected individuals to ventricular arrhythmias and sudden death. Dysfunction of the human ether-a-go-go-related gene (hERG)-encoded rapidly activating delayed rectifier K(+) channel (IKr) is a major cause of LQTS. The expression of hERG channels is controlled by anterograde trafficking of newly synthesized channels to and retrograde degradation of existing channels from the plasma membrane. We have previously shown that the E3 ubiquitin (Ub) ligase Nedd4-2 (neural precursor cell expressed developmentally down-regulated protein 4-2) targets the PY motif of hERG channels to initiate channel degradation. Although both immature and mature hERG channels contain the PY motif, Nedd4-2 selectively mediates the degradation of mature hERG channels. In the present study, we demonstrate that Nedd4-2 is directed to specific cellular compartments by the Nedd4 family interacting proteins, Nedd4 family-interacting protein 1 (Ndfip1) and Ndfip2. Ndfip1 is primarily localized in the Golgi apparatus where it recruits Nedd4-2 to mediate the degradation of mature hERG proteins during channel trafficking to the plasma membrane. Although Ndfip2 directs Nedd4-2 to the Golgi apparatus, it also recruits Nedd4-2 to the multivesicular bodies (MVBs), which may impair MVB function and impede the degradation of mature hERG proteins mediated by Nedd4-2. These findings extend our understanding of hERG channel regulation and provide information which may be useful for the rescue of impaired hERG function in LQTS. PMID- 26363004 TI - Paracrine Engineering of Human Cardiac Stem Cells With Insulin-Like Growth Factor 1 Enhances Myocardial Repair. AB - BACKGROUND: Insulin-like growth factor 1 (IGF-1) activates prosurvival pathways and improves postischemic cardiac function, but this key cytokine is not robustly expressed by cultured human cardiac stem cells. We explored the influence of an enhanced IGF-1 paracrine signature on explant-derived cardiac stem cell-mediated cardiac repair. METHODS AND RESULTS: Receptor profiling demonstrated that IGF-1 receptor expression was increased in the infarct border zones of experimentally infarcted mice by 1 week after myocardial infarction. Human explant-derived cells underwent somatic gene transfer to overexpress human IGF-1 or the green fluorescent protein reporter alone. After culture in hypoxic reduced-serum media, overexpression of IGF-1 enhanced proliferation and expression of prosurvival transcripts and prosurvival proteins and decreased expression of apoptotic markers in both explant-derived cells and cocultured neonatal rat ventricular cardiomyocytes. Transplant of explant-derived cells genetically engineered to overexpress IGF-1 into immunodeficient mice 1 week after infarction boosted IGF-1 content within infarcted tissue and long-term engraftment of transplanted cells while reducing apoptosis and long-term myocardial scarring. CONCLUSIONS: Paracrine engineering of explant-derived cells to overexpress IGF-1 provided a targeted means of improving cardiac stem cell-mediated repair by enhancing the long-term survival of transplanted cells and surrounding myocardium. PMID- 26363005 TI - Effects of Cardiac Resynchronization Therapy on Cardiac Remodeling and Contractile Function: Results From Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction (REVERSE). AB - BACKGROUND: Cardiac resynchronization therapy results in improved ejection fraction in patients with heart failure. We sought to determine whether these effects were mediated by changes in contractility, afterload, or volumes. METHODS AND RESULTS: In 610 patients with New York Heart Association class I/II heart failure from the Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction (REVERSE) study, we performed detailed quantitative echocardiography assessment prior to and following cardiac resynchronization therapy. We derived measures of contractility (the slope [end-systolic elastance] and the volume intercept of the end-systolic pressure-volume relationship, stroke work, and preload recruitable stroke work), measures of arterial load and ventricular-arterial coupling, and measures of chamber size (volume intercept, end-systolic and end-diastolic volumes). At 6 and 12 months, cardiac resynchronization therapy was associated with a reduction in the volume intercept and end-systolic and end-diastolic volumes (P<0.01). There were no consistent effects on end-systolic elastance, stroke work, preload recruitable stroke work, or ventricular-arterial coupling. In the active cardiac resynchronization therapy population, baseline measures of arterial load were associated with the clinical composite score (odds ratio 1.30, 95% CI 1.04 to 1.63, P=0.02). The volume intercept was associated with mortality (hazard ratio 1.90, 95% CI 1.01 to 3.59, P=0.047) and more modestly with the combined end point of mortality or heart failure hospitalization (hazard ratio 1.48, 95% CI 0.8 to 2.25, P=0.06). In contrast, end-systolic elastance, stroke work, preload recruitable stroke work, and ventricular-arterial coupling were not associated with any outcomes. CONCLUSION: In patients with NYHA Class I/II heart failure, cardiac resynchronization therapy exerts favorable changes in left ventricular end systolic and end-diastolic volumes and the volume intercept. The volume intercept may be useful to gain insight into prognosis in heart failure. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00271154. PMID- 26363006 TI - A TDO2-AhR signaling axis facilitates anoikis resistance and metastasis in triple negative breast cancer. AB - The ability of a cancer cell to develop resistance to anoikis, a programmed cell death process triggered by substratum detachment, is a critical step in the metastatic cascade. Triple-negative breast cancers (TNBC) exhibit higher rates of metastasis after diagnosis, relative to estrogen-positive breast cancers, but while TNBC cells are relatively more resistant to anoikis, the mechanisms involved are unclear. Through gene expression and metabolomic profiling of TNBC cells in forced suspension culture, we identified a molecular pathway critical for anchorage-independent cell survival. TNBC cells in suspension upregulated multiple genes in the kynurenine pathway of tryptophan catabolism, including the enzyme tryptophan 2,3-dioxygenase (TDO2), in an NF-kappaB-dependent manner. Kynurenine production mediated by TDO2 in TNBC cells was sufficient to activate aryl hydrocarbon receptor (AhR), an endogenous kynurenine receptor. Notably, pharmacologic inhibition or genetic attenuation of TDO2 or AhR increased cellular sensitivity to anoikis, and also reduced proliferation, migration, and invasion of TNBC cells. In vivo, TDO2 inhibitor-treated TNBC cells inhibited colonization of the lung, suggesting that TDO2 enhanced metastatic capacity. In clinical specimens of TNBC, elevated expression of TDO2 was associated with increased disease grade, estrogen receptor-negative status, and shorter overall survival. Our results define an NF-kappaB-regulated signaling axis that promotes anoikis resistance, suggest functional connections with inflammatory modulation by the kynurenine pathway, and highlight TDO2 as an attractive target for treatment of this aggressive breast cancer subtype. PMID- 26363007 TI - CD73 is associated with poor prognosis in high-grade serous ovarian cancer. AB - The cell surface nucleotidase CD73 is an immunosuppressive enzyme involved in tumor progression and metastasis. Although preclinical studies suggest that CD73 can be targeted for cancer treatment, the clinical impact of CD73 in ovarian cancer remains unclear. In this study, we investigated the prognostic value of CD73 in high-grade serous (HGS) ovarian cancer using gene and protein expression analyses. Our results demonstrate that high levels of CD73 are significantly associated with shorter disease-free survival and overall survival in patients with HGS ovarian cancer. Furthermore, high levels of CD73 expression in ovarian tumor cells abolished the good prognosis associated with intraepithelial CD8(+) cells. Notably, CD73 gene expression was highest in the C1/stromal molecular subtype of HGS ovarian cancer and positively correlated with an epithelial-to mesenchymal transition gene signature. Moreover, in vitro studies revealed that CD73 and extracellular adenosine enhance ovarian tumor cell growth as well as expression of antiapoptotic BCL-2 family members. Finally, in vivo coinjection of ID8 mouse ovarian tumor cells with mouse embryonic fibroblasts showed that CD73 expression in fibroblasts promotes tumor immune escape and thereby tumor growth. In conclusion, our study highlights a role for CD73 as a prognostic marker of patient survival and also as a candidate therapeutic target in HGS ovarian cancers. PMID- 26363008 TI - Generation of a mouse model of atypical teratoid/rhabdoid tumor of the central nervous system through combined deletion of Snf5 and p53. AB - Malignant rhabdoid tumors arise in several anatomic locations and are associated with poor outcomes. In the brain, these tumors are known as atypical teratoid/rhabdoid tumors (AT/RT). While genetically engineered models for malignant rhabdoid tumors exist, none of them recapitulate AT/RT, for which preclinical models remain lacking. In the majority of AT/RT, LOH occurs at the genetic locus SNF5 (Ini1/BAF47/Smarcb1), which functions as a subunit of the SWI/SNF chromatin-remodeling complex and a tumor suppressor in familial and sporadic malignant rhabdoid tumors. Therefore, we generated mice in which Snf5 was ablated specifically in nestin-positive and/or glial fibrillary acid protein (GFAP)-positive progenitor cells of the developing central nervous system (CNS). Snf5 ablation in nestin-positive cells resulted in early lethality that could not be rescued by loss of p53. However, Snf5 ablation in GFAP-positive cells caused a neurodegenerative phenotype exacerbated by p53 loss. Notably, these double mutants exhibited AT/RT development, associated with an earlier failure in granule neuron migration in the cerebellum, reduced neuronal projections in the hippocampus, degeneration of the corpus callosum, and ataxia and seizures. Gene expression analysis confirmed that the tumors that arose in Snf5/p53 mutant mice were distinct from other neural tumors and most closely resembled human AT/RT. Our findings uncover a novel role for Snf5 in oligodendrocyte generation and survival, and they offer evidence of the first genetically engineered mouse model for AT/RT in the CNS. PMID- 26363009 TI - Activation status of the pregnane X receptor influences vemurafenib availability in humanized mouse models. AB - Vemurafenib is a revolutionary treatment for melanoma, but the magnitude of therapeutic response is highly variable, and the rapid acquisition of resistance is frequent. Here, we examine how vemurafenib disposition, particularly through cytochrome P450-mediated oxidation pathways, could potentially influence these outcomes using a panel of knockout and transgenic humanized mouse models. We identified CYP3A4 as the major enzyme involved in the metabolism of vemurafenib in in vitro assays with human liver microsomes. However, mice expressing human CYP3A4 did not process vemurafenib to a greater extent than CYP3A4-null animals, suggesting that other pregnane X receptor (PXR)-regulated pathways may contribute more significantly to vemurafenib metabolism in vivo. Activation of PXR, but not of the closely related constitutive androstane receptor, profoundly reduced circulating levels of vemurafenib in humanized mice. This effect was independent of CYP3A4 and was negated by cotreatment with the drug efflux transporter inhibitor elacridar. Finally, vemurafenib strongly induced PXR activity in vitro, but only weakly induced PXR in vivo. Taken together, our findings demonstrate that vemurafenib is unlikely to exhibit a clinically significant interaction with CYP3A4, but that modulation of bioavailability through PXR-mediated regulation of drug transporters (e.g., by other drugs) has the potential to markedly influence systemic exposure and thereby therapeutic outcomes. PMID- 26363010 TI - Elevated expression of the C-type lectin CD93 in the glioblastoma vasculature regulates cytoskeletal rearrangements that enhance vessel function and reduce host survival. AB - Glioblastoma is an aggressive brain tumor characterized by an abnormal blood vasculature that is hyperpermeable. Here, we report a novel role for CD93 in regulating angiogenesis in this setting by modulating cell-cell and cell-matrix adhesion of endothelial cells. Tissue microarray analysis demonstrated that vascular expression of CD93 was correlated with poor survival in a clinical cohort of patients with high-grade astrocytic glioma. Similarly, intracranial growth in the GL261 mouse model of glioma was delayed significantly in CD93(-/-) hosts, resulting in improved survival compared with wild-type mice. This effect was associated with increased vascular permeability and decreased vascular perfusion of tumors, indicating reduced vessel functionality in the absence of CD93. RNAi-mediated attenuation of CD93 in endothelial cells diminished VEGF induced tube formation in a three-dimensional collagen gel. CD93 was required for efficient endothelial cell migration and proper cell polarization in vitro. Further, in endothelial cells where CD93 was attenuated, decreased cell spreading led to a severe reduction in cell adhesion, a lack of proper cell contacts, a loss of VE-cadherin, and aberrant actin stress fiber formation. Our results identify CD93 as a key regulator of glioma angiogenesis and vascular function, acting via cytoskeletal rearrangements required for cell-cell and cell-matrix adhesion. PMID- 26363011 TI - YAP promotes malignant progression of Lkb1-deficient lung adenocarcinoma through downstream regulation of survivin. AB - The serine/threonine kinase LKB1 is a well-characterized tumor suppressor that governs diverse cellular processes, including growth, polarity, and metabolism. Somatic-inactivating mutations in LKB1 are observed in about 15% to 30% of non small cell lung cancers (NSCLC). LKB1 inactivation confers lung adenocarcinomas (ADC) with malignant features that remain refractory to therapeutic intervention. YAP activation has been linked to LKB1 deficiency, but the role of YAP in lung ADC formation and progression is uncertain. In this study, we showed that ectopic expression of YAP in type II alveolar epithelial cells led to hyperplasia in mouse lungs. YAP overexpression in the Kras(G12D) lung cancer mouse model accelerated lung ADC progression. Conversely, YAP deletion dramatically delayed the progression of lung ADC in LKB1-deficient Kras(G12D) mice. Mechanistic studies identified the antiapoptotic oncoprotein survivin as the downstream mediator of YAP responsible for promoting malignant progression of LKB1-deficient lung ADC. Collectively, our findings identify YAP as an important contributor to lung cancer progression, rationalizing YAP inhibition in the context of LKB1 deficiency as a therapeutic strategy to treat lung ADC. PMID- 26363013 TI - Teaching microbiology to undergraduate students in the humanities and the social sciences. AB - This paper summarizes my experiences teaching a 28-hour course on the bacterial world for undergraduate students in the humanities and the social sciences at the Hebrew University of Jerusalem. This course was offered in the framework of a program in which students must obtain credit points for courses offered by other faculties to broaden their education. Most students had little biology in high school and had never been exposed to the basics of chemistry. Using a historical approach, highlighting the work of pioneers such as van Leeuwenhoek, Koch, Fleming, Pasteur, Winogradsky and Woese, I covered a broad area of general, medical, environmental and evolutionary microbiology. The lectures included basic concepts of organic and inorganic chemistry necessary to understand the principles of fermentations and chemoautotrophy, and basic molecular biology to explain biotechnology using transgenic microorganisms and molecular phylogeny. Teaching the basics of microbiology to intelligent students lacking any background in the natural sciences was a rewarding experience. Some students complained that, in spite of my efforts, basic concepts of chemistry remained beyond their understanding. But overall the students' evaluation showed that the course had achieved its goal. PMID- 26363012 TI - Radioprotection of IDH1-Mutated Cancer Cells by the IDH1-Mutant Inhibitor AGI 5198. AB - Isocitrate dehydrogenase 1 (IDH1) is mutated in various types of human cancer to IDH1(R132H), a structural alteration that leads to catalysis of alpha ketoglutarate to the oncometabolite D-2-hydroxyglutarate. In this study, we present evidence that small-molecule inhibitors of IDH1(R132H) that are being developed for cancer therapy may pose risks with coadministration of radiotherapy. Cancer cells heterozygous for the IDH1(R132H) mutation exhibited less IDH-mediated production of NADPH, such that after exposure to ionizing radiation (IR), there were higher levels of reactive oxygen species, DNA double strand breaks, and cell death compared with IDH1 wild-type cells. These effects were reversed by the IDH1(R132H) inhibitor AGI-5198. Exposure of IDH1 wild-type cells to D-2-hydroxyglutarate was sufficient to reduce IDH-mediated NADPH production and increase IR sensitivity. Mechanistic investigations revealed that the radiosensitivity of heterozygous cells was independent of the well-described DNA hypermethylation phenotype in IDH1-mutated cancers. Thus, our results argue that altered oxidative stress responses are a plausible mechanism to understand the radiosensitivity of IDH1-mutated cancer cells. Further, they offer an explanation for the relatively longer survival of patients with IDH1-mutated tumors, and they imply that administration of IDH1(R132H) inhibitors in these patients may limit irradiation efficacy in this setting. PMID- 26363014 TI - Detection of outer membrane vesicles in Synechocystis PCC 6803. AB - It has been well established that many species of Gram-negative bacteria release nanoscale outer membrane vesicles (OMVs) during normal growth. Furthermore, the roles of these structures in heterotrophic bacteria have been extensively characterized. However, little is known about the existence or function of OMVs in photoautotrophs. In the present study, we report for the first time the production of OMVs by the model photosynthetic organism Synechocystis sp. PCC 6803, a species of biotechnological importance. We detected extracellular proteins and lipids in cell-free supernatants derived from Synechocystis culture, yet the cytoplasmic and thylakoid membrane markers NADH oxidase and chlorophyll were absent. This indicated that the extracellular proteins and lipids derived from the outer membrane, and not from cell lysis. Furthermore, we identified spherical structures within the expected size range of OMVs in Synechocystis culture using scanning electron microscopy. Taken together, these results suggest that the repertoire of Gram-negative bacteria that are known to produce OMVs may be expanded to include Synechocystis PCC6803. Because of the considerable genetic characterization of Synechocystis in particular, our discovery has the potential to support novel biotechnological applications as well. PMID- 26363015 TI - Inoculum optimization of Clostridium beijerinckii for reproducible growth. AB - Spore-forming solventogenic Clostridium spp. are receiving renewed attention due to their butanol production abilities. However, there is an absence of literature describing the preparation of dense, vigorous and homogeneous seed cultures of Clostridium spp., guaranteeing reproducibility during fermentation. Therefore, we performed a series of growth experiments of Clostridium beijerinckii NCIMB 8052 and its offspring SA-1 to evaluate the influence of inoculum age (harvest time) on the subsequent population's maximum specific growth rate, as a signal of population homogeneity. The organisms were cultivated in Reinforced Clostridial Medium and supplemented sweet sorghum juice. The best inoculum ages coincided with the late-exponential growth phase: between 9 and 11 h in the conditions tested. Additionally, the harvest time was delayed up to 4 h by pre-adapting the seed culture with 0.75 g L(-1) butyric acid. These findings were validated by performing a series of bench-top batch fermentations showcasing reproducibility in growth kinetics with 95% confidence limits. Overall, these experiments allowed us to understand the transient nature of seed cultures of C. beijerinckii NCIMB 8052 and SA-1, while enabling reproducibility and consistent culture performance. PMID- 26363016 TI - A membrane transporter required for 3-hydroxybutyrate uptake during the early sporulation stage in Bacillus subtilis. AB - Exogenous 3-hydroxybutyrate can be utilized by a variety of soil bacteria as a carbon and energy source. However, the membrane transporter responsible for 3 hydroxybutyrate uptake remains unidentified. The Bacillus subtilis strain 168 gene yxjC (herein renamed hbuT) encodes a putative gluconate transporter GntT type membrane transporter with a previously unknown function. hbuT is organized within the same operon with genes that are used for metabolism of 3 hydroxybutyrate. Here we report that a null mutation of hbuT reduced uptake of 3 hydroxybutyrate by B. subtilis cells grown in nutrient sporulation medium. The SigE-controlled HbuT transporter apparently plays a major role in the uptake of 3 hydroxybutyrate. Uptake of 3-hydroxybutyrate by the HbuT transporter occurred in a specific manner at the early sporulation stage. SigE-controlled hbuT expression and 3-hydroxybutyrate uptake were also subject to CcpA-mediated glucose repression. hbuT expression was not induced by exogenous 3-hydroxybutyrate and B. subtilis cells could not utilize 3-hydroxybutyrate as a sole carbon source for growth. HbuT homologs are present in a wide variety of Gram-positive Bacillus species, some Gram-negative Acinetobacter species and a small group of other bacteria. This is the first tentative identification of a membrane transporter responsible for the uptake of 3-hydroxybutyrate in bacteria. PMID- 26363017 TI - A novel DNA-binding protein from Campylobacter jejuni bacteriophage NCTC12673. AB - We previously suggested that the double-stranded genomic DNA of Campylobacter jejuni bacteriophage NCTC12673 was complexed with proteins. Mass spectrometry of peptides obtained from tryptic digests of purified phage DNA indicated that phage protein Gp001 co-purified with the DNA. Gp001 is an acidic protein that lacks any obvious homology or conserved domains found in known DNA-binding proteins. The DNA-binding ability of recombinant Gp001 was examined using an electrophoretic mobility shift assay. Slow DNA-Gp001 complex formation was observed at pH 5.5, but not at neutral or basic pH. This nucleoprotein complex had difficulty entering agarose gels used in the assay while proteinase K pretreatment released the DNA from the complex. No mobility shift was observed when the DNA was immediately subjected to electrophoresis after mixing with Gp001, even if both components were separately pre-incubated at pH 5.5. The complexed DNA was unable to transform chemically competent Escherichia coli cells and was less susceptible to degradation by nucleases. The formation of Gp001-DNA complexes at low pH may provide a mechanism for maintaining DNA integrity while the phage pursues its host through the gastrointestinal tract. Also, this feature can potentially be used to improve DNA delivery protocols applied in gene therapy. PMID- 26363018 TI - Engineering of Corynebacterium glutamicum for growth and succinate production from levoglucosan, a pyrolytic sugar substrate. AB - Thermochemical processing provides continuous production of bio-oils from lignocellulosic biomass. Levoglucosan, a pyrolytic sugar substrate C6H10O5 in a bio-oil, has been used for ethanol production using engineered Escherichia coli. Here we provide the first example for succinate production from levoglucosan with Corynebacterium glutamicum, a well-known industrial amino acid producer. Heterologous expression of a gene encoding a sugar kinase from Lipomyces starkeyi, Gibberella zeae or Pseudomonas aeruginosa was employed for levoglucosan conversion in C. glutamicum because the wild type was unable to utilize levoglucosan as sole carbon source. As result, expression of a levoglucosan kinase (LGK) of L. starkeyi only enabled growth with levoglucosan as sole carbon source in CgXII minimal medium by catalyzing conversion of levoglucosan to glucose-6-phosphate. Subsequently, the lgk gene was expressed in an aerobic succinate producer of C. glutamicum, strain BL-1. The recombinant strain showed a higher succinate yield (0.25 g g(-1)) from 2% (w/v) levoglucosan than the reference strain BL-1 from 2% (w/v) glucose (0.19 g g(-1)), confirming that levoglucosan is an attractive carbon substrate for C. glutamicum producer strains. In summary, we demonstrated that a pyrolytic sugar could be a potential carbon source for microbial cell factories. PMID- 26363019 TI - Bidirectional signaling in the competence regulatory pathway of Streptococcus mutans. AB - Streptococcus mutans expresses comX (also known as sigX), which encodes a sigma factor that is required for development of genetic competence, in response to the peptide signals XIP and CSP and environmental factors. XIP (sigX inducing peptide) is derived from ComS and activates comX unimodally in chemically defined media via the ComRS system. CSP (competence stimulating peptide) activates comX bimodally in peptide-rich media through the ComDE two-component system. However, CSP-ComDE activation of comX is indirect and involves ComRS. Therefore, the bimodality of CSP-dependent activation of comX may arise from either ComRS or ComDE. Here we study, at the single-cell level, how genes in the CSP signaling pathway respond to CSP, XIP and media. Our data indicate that activation of comX stimulates expression of comE. In addition, activation of comE requires intact comR and comS genes. Therefore, not only does CSP-ComDE stimulate the ComRS pathway to activate comX expression, but ComRS activation of comX also stimulates expression of the CSP-ComDE pathway and its regulon. The results demonstrate the mutual interconnection of the signaling pathways that control bacteriocin expression (ComDE) and genetic competence (ComRS), both of which are linked to lytic and virulence behaviors. PMID- 26363020 TI - Co-LncRNA: investigating the lncRNA combinatorial effects in GO annotations and KEGG pathways based on human RNA-Seq data. AB - Long non-coding RNAs (lncRNAs) are emerging as key regulators of diverse biological processes and diseases. However, the combinatorial effects of these molecules in a specific biological function are poorly understood. Identifying co expressed protein-coding genes of lncRNAs would provide ample insight into lncRNA functions. To facilitate such an effort, we have developed Co-LncRNA, which is a web-based computational tool that allows users to identify GO annotations and KEGG pathways that may be affected by co-expressed protein-coding genes of a single or multiple lncRNAs. LncRNA co-expressed protein-coding genes were first identified in publicly available human RNA-Seq datasets, including 241 datasets across 6560 total individuals representing 28 tissue types/cell lines. Then, the lncRNA combinatorial effects in a given GO annotations or KEGG pathways are taken into account by the simultaneous analysis of multiple lncRNAs in user-selected individual or multiple datasets, which is realized by enrichment analysis. In addition, this software provides a graphical overview of pathways that are modulated by lncRNAs, as well as a specific tool to display the relevant networks between lncRNAs and their co-expressed protein-coding genes. Co-LncRNA also supports users in uploading their own lncRNA and protein-coding gene expression profiles to investigate the lncRNA combinatorial effects. It will be continuously updated with more human RNA-Seq datasets on an annual basis. Taken together, Co LncRNA provides a web-based application for investigating lncRNA combinatorial effects, which could shed light on their biological roles and could be a valuable resource for this community. Database URL: http://www.bio-bigdata.com/Co-LncRNA/. PMID- 26363021 TI - LncReg: a reference resource for lncRNA-associated regulatory networks. AB - Long non-coding RNAs (lncRNAs) are critical in the regulation of various biological processes. In recent years, plethora of lncRNAs have been identified in mammalian genomes through different approaches, and the researchers are constantly reporting the regulatory roles of these lncRNAs, which leads to complexity of literature about particular lncRNAs. Therefore, for the convenience of the researchers, we collected regulatory relationships of the lncRNAs and built a database called 'LncReg'. This database is developed by collecting 1081 validated lncRNA-associated regulatory entries, including 258 non-redundant lncRNAs and 571 non-redundant genes. With regulatory relationships information, LncReg can provide overall perspectives of regulatory networks of lncRNAs and comprehensive data for bioinformatics research, which is useful for understanding the functional roles of lncRNAs. Database URL: http://bioinformatics.ustc.edu.cn/lncreg/. PMID- 26363022 TI - The Impact of Childhood Hearing Loss on the Family: Mothers' and Fathers' Stress and Coping Resources. AB - Parenting children who are deaf or hard of hearing (D/HH) presents unique long term challenges that can place the parents at a greater risk for elevated levels of parenting stress. Adaptation of families to the various challenges presented by childhood hearing loss is influenced by their personal and social coping resources available for managing these stressors and challenges. The current study examined differences in parenting stress and personal (i.e., acceptance of the child who is D/HH and parents' sense of parenting self-efficacy) and social (i.e., formal and informal social support) coping resources between mothers and fathers of children who are D/HH in the Arab sector in Israel. Further, the study examined the relations between coping resources and parenting stress among these parents. Participants included 30 Israeli Arab mother-father couples (n = 60) having a child who is D/HH aged 3-8 years. Findings revealed no significant differences between mothers and fathers regarding parenting stress, child acceptance, or parental support systems. However, mothers reported significantly higher self-efficacy. In addition, correlation analysis indicated that higher coping resources decreased parenting stress levels. Theoretical and practical implications of parental gender in the context of cultural background are discussed regarding parent intervention programs. PMID- 26363023 TI - Mechanisms involved in the inhibition of glycolysis by cyanide and antimycin A in Candida albicans and its reversal by hydrogen peroxide. A common feature in Candida species. AB - In Candida albicans, cyanide and antimycin A inhibited K(+) transport, not only with ethanol-O2 as the substrate, but also with glucose. The reason for this was that they inhibited not only respiration, but also fermentation, decreasing ATP production. Measurements of oxygen levels in cell suspensions allowed identification of the electron pathways involved. NADH fluorescence levels increased in the presence of the inhibitors, indirectly indicating lower levels of NAD(+) and so pointing to glyceraldehyde-3-phosphate dehydrogenase as the limiting step responsible for the inhibition of glycolysis, which was confirmed by the levels of glycolytic intermediaries. The cyanide effect could be reversed by hydrogen peroxide, mainly due to an activity by which H2O2 can be reduced by electrons flowing from NADH through a pathway that can be inhibited by antimycin A, and appears to be a cytochrome c peroxidase. Therefore, the inhibition of glycolysis by the respiratory inhibitors seems to be due to the decreased availability of NAD(+), resulting in a decreased activity of glyceraldehyde-3 phosphate dehydrogenase. Compartmentalization of pyridine nucleotides in favor of the mitochondria can contribute to explaining the low fermentation capacity of C. albicans. Similar results were obtained with three C. albicans strains, Candida dubliniensis and, to a lower degree, Candida parapsilosis. PMID- 26363026 TI - Low-Turnover Drug Molecules: A Current Challenge for Drug Metabolism Scientists. AB - In vitro assays using liver subcellular fractions or suspended hepatocytes for characterizing the metabolism of drug candidates play an integral role in the optimization strategy employed by medicinal chemists. However, conventional in vitro assays have limitations in their ability to predict clearance and generate metabolites for low-turnover (slowly metabolized) drug molecules. Due to a rapid loss in the activity of the drug-metabolizing enzymes, in vitro incubations are typically performed for a maximum of 1 hour with liver microsomes to 4 hours with suspended hepatocytes. Such incubations are insufficient to generate a robust metabolic response for compounds that are slowly metabolized. Thus, the challenge of accurately estimating low human clearance with confidence has emerged to be among the top challenges that drug metabolism scientists are confronted with today. In response, investigators have evaluated novel methodologies to extend incubation times and more sufficiently measure metabolism of low-turnover drugs. These methods include plated human hepatocytes in monoculture, and a novel in vitro methodology using a relay of sequential incubations with suspended cryopreserved hepatocytes. In addition, more complex in vitro cellular models, such as HepatoPac (Hepregen, Medford, MA), a micropatterned hepatocyte-fibroblast coculture system, and the HuREL (Beverley Hills, CA) hepatic coculture system, have been developed and characterized that demonstrate prolonged enzyme activity. In this review, the advantages and disadvantages of each of these in vitro methodologies as it relates to the prediction of clearance and metabolite identification will be described in an effort to provide drug metabolism scientists with the most up-to-date experimental options for dealing with the complex issue of low-turnover drug candidates. PMID- 26363027 TI - A robust AMMI model for the analysis of genotype-by-environment data. AB - MOTIVATION: One of the most widely used models to analyse genotype-by-environment data is the additive main effects and multiplicative interaction (AMMI) model. Genotype-by-environment data resulting from multi-location trials are usually organized in two-way tables with genotypes in the rows and environments (location year combinations) in the columns. The AMMI model applies singular value decomposition (SVD) to the residuals of a specific linear model, to decompose the genotype-by-environment interaction (GEI) into a sum of multiplicative terms. However, SVD, being a least squares method, is highly sensitive to contamination and the presence of even a single outlier, if extreme, may draw the leading principal component towards itself resulting in possible misinterpretations and in turn lead to bad practical decisions. Since, as in many other real-life studies the distribution of these data is usually not normal due to the presence of outlying observations, either resulting from measurement errors or sometimes from individual intrinsic characteristics, robust SVD methods have been suggested to help overcome this handicap. RESULTS: We propose a robust generalization of the AMMI model (the R-AMMI model) that overcomes the fragility of its classical version when the data are contaminated. Here, robust statistical methods replace the classic ones to model, structure and analyse GEI. The performance of the robust extensions of the AMMI model is assessed through a Monte Carlo simulation study where several contamination schemes are considered. Applications to two real plant datasets are also presented to illustrate the benefits of the proposed methodology, which can be broadened to both animal and human genetics studies. AVAILABILITY AND IMPLEMENTATION: Source code implemented in R is available in the supplementary material under the function r-AMMI. CONTACT: paulocanas@gmail.com SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26363028 TI - BamHash: a checksum program for verifying the integrity of sequence data. AB - SUMMARY: Large resequencing projects require a significant amount of storage for raw sequences, as well as alignment files. Because the raw sequences are redundant once the alignment has been generated, it is possible to keep only the alignment files. We present BamHash, a checksum based method to ensure that the read pairs in FASTQ files match exactly the read pairs stored in BAM files, regardless of the ordering of reads. BamHash can be used to verify the integrity of the files stored and discover any discrepancies. Thus, BamHash can be used to determine if it is safe to delete the FASTQ files storing raw sequencing read after alignment, without the loss of data. AVAILABILITY AND IMPLEMENTATION: The software is implemented in C++, GPL licensed and available at https://github.com/DecodeGenetics/BamHash CONTACT: pmelsted@hi.is. PMID- 26363029 TI - An algorithm for automated layout of process description maps drawn in SBGN. AB - MOTIVATION: Evolving technology has increased the focus on genomics. The combination of today's advanced techniques with decades of molecular biology research has yielded huge amounts of pathway data. A standard, named the Systems Biology Graphical Notation (SBGN), was recently introduced to allow scientists to represent biological pathways in an unambiguous, easy-to-understand and efficient manner. Although there are a number of automated layout algorithms for various types of biological networks, currently none specialize on process description (PD) maps as defined by SBGN. RESULTS: We propose a new automated layout algorithm for PD maps drawn in SBGN. Our algorithm is based on a force-directed automated layout algorithm called Compound Spring Embedder (CoSE). On top of the existing force scheme, additional heuristics employing new types of forces and movement rules are defined to address SBGN-specific rules. Our algorithm is the only automatic layout algorithm that properly addresses all SBGN rules for drawing PD maps, including placement of substrates and products of process nodes on opposite sides, compact tiling of members of molecular complexes and extensively making use of nested structures (compound nodes) to properly draw cellular locations and molecular complex structures. As demonstrated experimentally, the algorithm results in significant improvements over use of a generic layout algorithm such as CoSE in addressing SBGN rules on top of commonly accepted graph drawing criteria. AVAILABILITY AND IMPLEMENTATION: An implementation of our algorithm in Java is available within ChiLay library (https://github.com/iVis-at-Bilkent/chilay). CONTACT: ugur@cs.bilkent.edu.tr or dogrusoz@cbio.mskcc.org SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26363031 TI - Mutagenic, surviving and tumorigenic effects of follicular fluid in the context of p53 loss: initiation of fimbria carcinogenesis. AB - Ovulation is the strongest risk factor for ovarian high-grade serous carcinoma (HGSC) that largely originates from the fallopian tube fimbriae and always carries loss-of-function mutations of TP53 in both early and late lesions. Mature ovarian follicle contains high level of reactive oxygen species (ROS). When released from ovulation, follicular fluid (FF) bathes the fimbriae and may lead to DNA double-strand break (DSB) and neoplastic transformation. In this study, we examined the mutagenic and tumorigenic activities of human pre-ovulatory FFs. A subset (6/11) of FFs was found with high levels of ROS whereas the antioxidant capacities were indifferent. These ROS(high) FFs induced intracellular ROS and DSBs in the secretory cell population of fimbriae epithelium. When p53 and Rb were turned down, the FF-exposed secretory cells overcame apoptosis and expanded the population carrying ROS and DSB. The cancer initiation and promotion effects of FF were further recapitulated in Trp53 (-/-) mice. When introduced into the mammary fat pad, ROS(high) but not ROS(low) FFs induced early-onset B-cell lymphoma. Cotreatment with physiological concentration of melatonin, a potent antioxidant, ameliorated the mutagenic and tumorigenic effect of ROS(high) FF in vitro and in vivo. The study revealed ROS and mitogens in mature ovarian follicles could initiate the transformation of fimbria epithelium in the context of p53 loss and melatonin is a potent preventive agent. PMID- 26363030 TI - Peripheral blood mitochondrial DNA copy number, length heteroplasmy and breast cancer risk: a replication study. AB - Oxidative stress has consistently been linked to breast carcinogenesis, and mitochondria play a significant role in regulating reactive oxygen species generation. In our previous study, we found that increased levels of mitochondrial DNA (mtDNA) copy number and the presence of mitochondrial length heteroplasmies in the hypervariable (HV) regions 1 and 2 (HV1 and HV2) in peripheral blood are associated with increased risk of breast cancer. In current study with 1000 breast cancer cases and 1000 healthy controls, we intended to replicate our previous findings. Overall, levels of mtDNA copy number were significantly higher in breast cancer cases than healthy controls (mean: 1.17 versus 0.94, P < 0.001). In the multivariate linear regression analysis, increased mtDNA copy number levels were associated with a 1.32-fold increased risk of breast cancer [adjusted odds ratio (OR) = 1.32, 95% confidence interval (CI) = 1.15-1.67]. Breast cancer cases were more likely to have HV1 and HV2 region length heteroplasmies than healthy controls (P < 0.001, respectively). The existence of HV1 and HV2 length heteroplasmies was associated with 2.01- and 1.63 folds increased risk of breast cancer (for HV1: OR = 2.01, 95% CI = 1.66-2.42; for HV2: OR = 1.63, 95% CI = 1.34-1.92). Additionally, joint effects among mtDNA copy number, HV1 and HV2 length heteroplasmies were observed. Our results are consistent with our previous findings and further support the roles of mtDNA copy number and mtDNA length heteroplasmies that may play in the development of breast cancer. PMID- 26363032 TI - Transgenic mice overexpressing arginase 1 in monocytic cell lineage are affected by lympho-myeloproliferative disorders and disseminated intravascular coagulation. AB - Arginase (ARG) is a metabolic enzyme present in two isoforms that hydrolyze l arginine to urea and ornithine. In humans, ARG isoform 1 is also expressed in cells of the myeloid lineage. ARG activity promotes tumour growth and inhibits T lymphocyte activation. However, the two ARG transgenic mouse lines produced so far failed to show such effects. We have generated, in two different genetic backgrounds, transgenic mice constitutively expressing ARG1 under the control of the CD68 promoter in macrophages and monocytes. Both heterozygous and homozygous transgenic mice showed a relevant increase in mortality at early age, compared with wild-type siblings (67/267 and 48/181 versus 8/149, respectively, both P < 0.005). This increase was due to high incidence of haematologic malignancies, in particular myeloid leukaemia, myeloid dysplasia, lymphomas and disseminated intravascular coagulation (DIC), diseases that were absent in wild-type mice. Atrophy of lymphoid organs due to reduction in T-cell compartment was also detected. Our results indicate that ARG activity may participate in the pathogenesis of lymphoproliferative and myeloproliferative disorders, suggest the involvement of alterations of L-arginine metabolism in the onset of DIC and confirm a role for the enzyme in regulating T-cell homeostasis. PMID- 26363034 TI - Placental ADAMTS-12 Levels in the Pathogenesis of Preeclampsia and Intrahepatic Cholestasis of Pregnancy. AB - Our aim was to determine whether placental A Disintegrin-like Metalloproteinase with ThromboSpondin motif 12 (ADAMTS-12), arylesterase (ARES) levels, total oxidant status (TOS), and total antioxidant status (TAS) differ in preeclampsia, intrahepatic cholestasis of pregnancy (ICP), and uncomplicated pregnancies or not. A prospective case-control study was carried out including 84 pregnant women (26 with ICP, 28 preeclamptic patients, and 30 healthy controls). Levels of ADAMTS-12, TAS, TOS, and ARES were studied in the supernatants of placental tissue homogenates. Placental ADAMTS-12 levels were distributed as 240.9 pg/mg in ICP, 289.7 pg/mg in preeclampsia, and 310.8 pg/mg in control groups. Levels of ADAMTS-12 (odds ratio = 6.509, 95% confidence interval:1.070-39.592, P = .042) in the placenta of the ICP were significantly lower than those in preeclampsia and control groups (P = .004), but no statistical significant difference was determined between preeclampsia and control groups. Decreased levels of placental ADAMTS-12 were found to be associated with ICP, suggesting a possible role of inflammation in the pathogenesis. PMID- 26363035 TI - Expression and Significance of WNT4 in Ectopic and Eutopic Endometrium of Human Endometriosis. AB - The objective was to investigate the expression of the WNT4 gene in ectopic endometrium and eutopic endometrium (EU) during endometriosis and the relationship of WNT4 expression with the menstrual cycle. Ectopic endometrium and EU tissues were collected from 30 women with pathologically confirmed endometriosis and 30 women without endometriosis. The WNT4 protein and messenger RNA (mRNA) expression levels were measured by fluorescence-based quantitative real-time polymerase chain reaction, immunohistochemistry, and Western blot methods. The expression of WNT4 was not significantly correlated with the menstrual cycle, and there were no significant differences when WNT4 expression in proliferative endometrium was compared with that in secretory endometrium within each group. There were no significant differences between the protein and mRNA expression of WNT4 in ectopic endometrium and in EU from participants with endometriosis. The WNT4 expression level in EU was significantly reduced compared with that in normal endometrium of the control group, even when analyzed by the menstrual cycle phase. WNT4 was also downregulated in ectopic lesions. This study provides further evidence supporting the theory of "EU determinism" in the pathogenesis of endometriosis. PMID- 26363036 TI - Capacitation-Associated Glycocomponents of Mammalian Sperm. AB - Mammalian fertilization is a series of events that are mostly carbohydrate mediated. The male gamete glycocomponents are extensively synthesized and modified during sperm development and sperm transport in the reproductive tracts. Freshly ejaculated mammalian sperm are required to undergo capacitation, which takes place in the female reproductive system, in order to become fully fertilizable. Several lines of evidence reveal changes in glycosylated sperm constituents during capacitation. Although the contributions of these molecular changes to capacitation are not completely understood, the presence, rearrangement, and/or modification of these sperm glycocomponents have been demonstrated to be important for fertilization. The following review summarizes mammalian sperm glycoconstituents, with emphasis on their molecular changes during capacitation. PMID- 26363033 TI - Identification of lung cancer histology-specific variants applying Bayesian framework variant prioritization approaches within the TRICL and ILCCO consortia. AB - Large-scale genome-wide association studies (GWAS) have likely uncovered all common variants at the GWAS significance level. Additional variants within the suggestive range (0.0001> P > 5*10(-8)) are, however, still of interest for identifying causal associations. This analysis aimed to apply novel variant prioritization approaches to identify additional lung cancer variants that may not reach the GWAS level. Effects were combined across studies with a total of 33456 controls and 6756 adenocarcinoma (AC; 13 studies), 5061 squamous cell carcinoma (SCC; 12 studies) and 2216 small cell lung cancer cases (9 studies). Based on prior information such as variant physical properties and functional significance, we applied stratified false discovery rates, hierarchical modeling and Bayesian false discovery probabilities for variant prioritization. We conducted a fine mapping analysis as validation of our methods by examining top ranking novel variants in six independent populations with a total of 3128 cases and 2966 controls. Three novel loci in the suggestive range were identified based on our Bayesian framework analyses: KCNIP4 at 4p15.2 (rs6448050, P = 4.6*10(-7)) and MTMR2 at 11q21 (rs10501831, P = 3.1*10(-6)) with SCC, as well as GAREM at 18q12.1 (rs11662168, P = 3.4*10(-7)) with AC. Use of our prioritization methods validated two of the top three loci associated with SCC (P = 1.05*10(-4) for KCNIP4, represented by rs9799795) and AC (P = 2.16*10(-4) for GAREM, represented by rs3786309) in the independent fine mapping populations. This study highlights the utility of using prior functional data for sequence variants in prioritization analyses to search for robust signals in the suggestive range. PMID- 26363037 TI - An efficient resampling method for calibrating single and gene-based rare variant association analysis in case-control studies. AB - For aggregation tests of genes or regions, the set of included variants often have small total minor allele counts (MACs), and this is particularly true when the most deleterious sets of variants are considered. When MAC is low, commonly used asymptotic tests are not well calibrated for binary phenotypes and can have conservative or anti-conservative results and potential power loss. Empirical p values obtained via resampling methods are computationally costly for highly significant p-values and the results can be conservative due to the discrete nature of resampling tests. Based on the observation that only the individuals containing minor alleles contribute to the score statistics, we develop an efficient resampling method for single and multiple variant score-based tests that can adjust for covariates. Our method can improve computational efficiency >1000-fold over conventional resampling for low MAC variant sets. We ameliorate the conservativeness of results through the use of mid-p-values. Using the estimated minimum achievable p-value for each test, we calibrate QQ plots and provide an effective number of tests. In analysis of a case-control study with deep exome sequence, we demonstrate that our methods are both well calibrated and also reduce computation time significantly compared with resampling methods. PMID- 26363038 TI - Synthetic Cannabinoid Receptor Agonists: a heterogeneous class of novel psychoactive substance with emerging risk of psychosis. PMID- 26363039 TI - Group cognitive-behavioural therapy may reduce symptoms and impairment in adolescents with attention-deficit/hyperactivity disorder. PMID- 26363040 TI - ECT is superior to pharmacotherapy for the short-term treatment of medication resistant inpatients with bipolar depression. PMID- 26363043 TI - Recurrent syncope: differential diagnosis and management. PMID- 26363041 TI - Family Model of Diabetes Education With a Pacific Islander Community. AB - PURPOSE: The purpose of the study was to use a community-based participatory research approach to pilot-test a family model of diabetes education conducted in participants' homes with extended family members. METHODS: The pilot test included 6 families (27 participants) who took part in a family model of diabetes self-management education (DSME) using an intervention-driven pre- and posttest design with the aim of improving glycemic control as measured by A1C. Questionnaires and additional biometric data were also collected. Researchers systematically documented elements of feasibility using participant observations and research field reports. RESULTS: More than three-fourths (78%) of participants were retained in the study. Posttest results indicated a 5% reduction in A1C across all participants and a 7% reduction among those with type 2 diabetes. Feasibility of an in-home model with extended family members was documented, along with observations and recommendations for further DSME adaptations related to blood glucose monitoring, physical activity, nutrition, and medication adherence. CONCLUSIONS: The information gained from this pilot helps to bridge the gap between knowledge of an evidence-based intervention and its actual implementation within a unique minority population with especially high rates of type 2 diabetes and significant health disparities. Building on the emerging literature of family models of DSME, this study shows that the family model delivered in the home had high acceptance and that the intervention was more accessible for this hard-to-reach population. PMID- 26363044 TI - Prognostic value of BNP in heart failure with preserved or reduced ejection fraction. PMID- 26363045 TI - The vulnerable atherosclerotic plaque: in vivo identification and potential therapeutic avenues. PMID- 26363046 TI - A Disorder of Qi: Breathing Exercise as a Cure for Neurasthenia in Japan, 1900 1945. AB - Neurasthenia became a common disease and caused widespread concern in Japan at the turn of the twentieth century, whereas only a couple of decades earlier the term "nerve" had been unfamiliar, if not unknown, to many Japanese. By exploring the theories and practices of breathing exercise-one of the most popular treatments for neurasthenia at the time-this paper attempts to understand how people who practiced breathing exercises for their nervous ills perceived, conceived, and accordingly cared for their nerves. It argues that they understood "nerve" based on their existing conceptions of qi Neurasthenia was for them a disorder of qi, although the qi had assumed modern appearances as blood and nervous current. The paper hopes to contribute to the understanding of how the concept of nerves has been accepted and assimilated in East Asia. It also points out the need to understand the varied cultures of nerves not only at the level of concept and metaphor, but also at the level of perception and experience. PMID- 26363047 TI - The History of Medicine in Medical Education. PMID- 26363048 TI - Assessment of patient engagement with a mobile application among service members in transition. AB - OBJECTIVE: This article examines engagement with a mobile application ("mCare") for wounded Service Members rehabilitating in their communities. Many had behavioral health problems, Traumatic Brain Injury (TBI), and/or post-traumatic stress disorder (PTS). The article also examines associations between Service Members' background characteristics and their engagement with mCare. MATERIALS AND METHODS: This analysis included participants who received mCare (n = 95) in a randomized controlled trial. mCare participants received status questionnaires daily for up to 36 weeks. Participant engagement encompasses exposure to mCare, percentage of questionnaires responded to, and response time. Participants were grouped by health status-that is, presence/absence of behavioral health problems, PTS, and/or TBI. Histograms and regression analyses examined engagement by participants' health status and background characteristics. RESULTS: Exposure to mCare did not differ by health status. Participants usually responded to >=60% of the questionnaires weekly, generally in <=10 h; however, participants with behavioral health problems had several weeks with <50% response and the longest response times. Total questionnaires responded to and response time did not differ statistically by health status. Older age and higher General Well-Being Schedule scores were associated with greater and faster response. DISCUSSION: The sustained response to the questionnaires suggests engagement. Overall level of response surpassed trends reported for American's usage of mobile applications. With a few exceptions, Service Members engaged with mCare irrespective of health status. CONCLUSION: Mobile health has the potential to increase the quantity and quality of patient-provider communications in a community-based, rehabilitation care setting, above that of standard care. PMID- 26363049 TI - Class A Scavenger Receptor-Mediated Double-Stranded RNA Internalization Is Independent of Innate Antiviral Signaling and Does Not Require Phosphatidylinositol 3-Kinase Activity. AB - dsRNA is a potent trigger of innate immune signaling, eliciting effects within virally infected cells and after release from dying cells. Given its inherent stability, extracellular dsRNA induces both local and systemic effects. Although the class A scavenger receptors (SR-As) mediate dsRNA entry, it is unknown whether they contribute to signaling beyond ligand internalization. In this study, we investigated whether SR-As contribute to innate immune signaling independent of the classic TLR and retinoic acid-inducible gene-I-like receptor (RLR) pathways. We generated a stable A549 human epithelial cell line with inducible expression of the hepatitis C virus protease NS3/4A, which efficiently cleaves TRIF and IFN-beta promoter stimulator 1, adaptors for TLR3 and the RLRs, respectively. Cells expressing NS3/4A and TLR3/MyD88/IFN-beta promoter stimulator 1(-/-) mouse embryonic fibroblasts completely lacked antiviral activity to extracellular dsRNA relative to control cells, suggesting that SR-As do not possess signaling capacity independent of TLR3 or the RLRs. Previous studies implicated PI3K signaling in SR-A-mediated activities and in downstream production of type I IFN. We found that SR-A-mediated dsRNA internalization occurs independent of PI3K activation, whereas downstream signaling leading to IFN production was partially dependent on PI3K activity. Overall, these findings suggest that SR-A-mediated dsRNA internalization is independent of innate antiviral signaling. PMID- 26363050 TI - alpha1-Antitrypsin Combines with Plasma Fatty Acids and Induces Angiopoietin-like Protein 4 Expression. AB - alpha1-Antitrypsin (A1AT) purified from human plasma upregulates expression and release of angiopoietin-like protein 4 (Angptl4) in adherent human blood monocytes and in human lung microvascular endothelial cells, providing a mechanism for the broad immune-regulatory properties of A1AT independent of its antiprotease activity. In this study, we demonstrate that A1AT (Prolastin), a potent inducer of Angptl4, contains significant quantities of the fatty acids (FA) linoleic acid (C18:2) and oleic acid (C18:1). However, only trace amounts of FAs were present in preparations that failed to increase Angplt4 expression, for example, A1AT (Zemaira) or M-type A1AT purified by affinity chromatography. FA pull-down assays with Western blot analysis revealed a FA-binding ability of A1AT. In human blood-adherent monocytes, A1AT-FA conjugates upregulated expression of Angptl4 (54.9-fold, p < 0.001), FA-binding protein 4 (FABP4) (11.4 fold, p < 0.001), and, to a lesser degree, FA translocase (CD36) (3.1-fold, p < 0.001) relative to A1AT devoid of FA (A1AT-0). These latter effects of A1AT-FA were blocked by inhibitors of peroxisome proliferator-activated receptor (PPAR) beta/delta (ST247) and PPARgamma (GW9662). When compared with controls, cell pretreatment with ST247 diminished the effect of A1AT-LA on Angptl4 mRNA (11.6- versus 4.1-fold, p < 0.001) and FABP4 mRNA (5.4- versus 2.8-fold, p < 0.001). Similarly, preincubation of cells with GW9662 inhibited inducing effect of A1AT LA on Angptl4 mRNA (by 2-fold, p < 0.001) and FABP4 mRNA (by 3-fold, p < 0.001). Thus, A1AT binds to FA, and it is this form of A1AT that induces Angptl4 and FABP4 expression via a PPAR-dependent pathway. These findings provide a mechanism for the unexplored area of A1AT biology independent of its antiprotease properties. PMID- 26363051 TI - Prenatal Allogeneic Tolerance in Mice Remains Stable Despite Potent Viral Immune Activation. AB - Transplanting stem cells before birth offers an unparalleled opportunity to initiate corrective treatment for numerous childhood diseases with minimal or no host conditioning. Although long-term engraftment has been demonstrated following in utero hematopoietic cellular transplantation during immune quiescence, it is unclear if prenatal tolerance becomes unstable with immune activation such as during a viral syndrome. Using a murine model of in utero hematopoietic cellular transplantation, the impact of an infection with lymphocytic choriomeningitis virus on prenatal allospecific tolerance was examined. The findings in this report illustrate that established mechanisms of donor-specific tolerance are strained during potent immune activation. Specifically, a transient reversal in the anergy of alloreactive lymphocytes is seen in parallel with the global immune response toward the virus. However, these changes return to baseline following resolution of the infection. Importantly, prenatal engraftment remains stable during and after immune activation. Collectively, these findings illustrate the robust nature of allospecific tolerance in prenatal mixed chimerism compared with models of postnatal chimerism and provides additional support for the prenatal approach to the treatment of congenital benign cellular disease. PMID- 26363052 TI - PU.1 Expression in T Follicular Helper Cells Limits CD40L-Dependent Germinal Center B Cell Development. AB - PU.1 is an ETS family transcription factor that is important for the development of multiple hematopoietic cell lineages. Previous work demonstrated a critical role for PU.1 in promoting Th9 development and in limiting Th2 cytokine production. Whether PU.1 has functions in other Th lineages is not clear. In this study, we examined the effects of ectopic expression of PU.1 in CD4(+) T cells and observed decreased expression of genes involved with the function of T follicular helper (Tfh) cells, including Il21 and Tnfsf5 (encoding CD40L). T cells from conditional mutant mice that lack expression of PU.1 in T cells (Sfpi1(lck-/-)) demonstrated increased production of CD40L and IL-21 in vitro. Following adjuvant-dependent or adjuvant-independent immunization, we observed that Sfpi1(lck-/-) mice had increased numbers of Tfh cells, increased germinal center B cells (GCB cells), and increased Ab production in vivo. This correlated with increased expression of IL-21 and CD40L in Tfh cells from Sfpi1(lck-/-) mice compared with control mice. Finally, although blockade of IL-21 did not affect GCB cells in Sfpi1(lck-/-) mice, anti-CD40L treatment of immunized Sfpi1(lck-/-) mice decreased GCB cell numbers and Ag-specific Ig concentrations. Together, these data indicate an inhibitory role for PU.1 in the function of Tfh cells, germinal centers, and Tfh-dependent humoral immunity. PMID- 26363053 TI - Phosphatase PP4 Negatively Regulates Type I IFN Production and Antiviral Innate Immunity by Dephosphorylating and Deactivating TBK1. AB - The effective recognition of viral infection and subsequent type I IFN production is essential for the host antiviral innate immune responses. The phosphorylation and activation of kinase TANK-binding kinase 1 (TBK1) plays crucial roles in the production of type I IFN mediated by TLR and retinoic acid-inducible gene I-like receptors. Type I IFN expression must be tightly regulated to prevent the development of immunopathological disorders. However, how the activated TBK1 is negatively regulated by phosphatases remains poorly understood. In this study, we identified a previously unknown role of protein phosphatase (PP)4 by acting as a TBK1 phosphatase. PP4 expression was upregulated in macrophages infected with RNA virus, vesicular stomatitis virus, and Sendai virus in vitro and in vivo. Knockdown of PP4C, the catalytic subunit of PP4, significantly increased type I IFN production in macrophages and dentritic cells triggered by TLR3/4 ligands, vesicular stomatitis virus, and Sendai virus, and thus inhibited virus replication. Similar results were also found in peritoneal macrophages with PP4C silencing in vivo and i.p. infection of RNA virus. Accordingly, ectopic expression of PP4C inhibited virus-induced type I IFN production and promoted virus replication. However, overexpression of a phosphatase-dead PP4C mutant abolished the inhibitory effects of wild-type PP4C on type I IFN production. Mechanistically, PP4 directly bound TBK1 upon virus infection, then dephosphorylated TBK1 at Ser(172) and inhibited TBK1 activation, and subsequently restrained IFN regulatory factor 3 activation, resulting in suppressed production of type I IFN and IFN-stimulated genes. Thus, serine/threonine phosphatase PP4 functions as a novel feedback negative regulator of RNA virus-triggered innate immunity. PMID- 26363054 TI - Sharpin Controls Osteogenic Differentiation of Mesenchymal Bone Marrow Cells. AB - The cytosolic protein Sharpin is a component of the linear ubiquitin chain assembly complex, which regulates NF-kappaB signaling in response to specific ligands, such as TNF-alpha. Its inactivating mutation in chronic proliferative dermatitis mutation (Cpdm) mice causes multiorgan inflammation, yet this phenotype is not transferable into wild-type mice by hematopoietic stem cell transfer. Recent evidence demonstrated that Cpdm mice additionally display low bone mass, and that this osteopenia is corrected by Tnf deletion. Because the cellular mechanism underlying this pathology, however, was still undefined, we performed a thorough skeletal phenotyping of Cpdm mice on the basis of nondecalcified histology and cellular and dynamic histomorphometry. We show that the trabecular and cortical osteopenia in Cpdm mice is solely explained by impaired bone formation, whereas osteoclastogenesis is unaffected. Consistently, Cpdm primary calvarial cells display reduced osteogenic capacity ex vivo, and the same was observed with CD11b(-) bone marrow cells. Unexpectedly, short-term treatment of these cultures with TNF-alpha did not reveal an impaired molecular response in the absence of Sharpin. Instead, genome-wide and gene-specific expression analyses revealed that Cpdm mesenchymal cells display increased responsiveness toward TNF-alpha-induced expression of specific cytokines, such as CXCL5, IL-1beta, and IL-6. Therefore, our data not only demonstrate that the skeletal defects of Cpdm mice are specifically caused by impaired differentiation of osteoprogenitor cells, they also suggest that increased cytokine expression in mesenchymal bone marrow cells contributes to the inflammatory phenotype of Cpdm mice. PMID- 26363056 TI - IL-4-Producing Dendritic Cells Induced during Schistosoma japonica Infection Promote Th2 Cells via IL-4-Dependent Pathway. AB - Although dendritic cells (DCs) have been widely demonstrated to play essential roles in initiation of Th2 responses in helminth infections and allergic reactions, the mechanisms remain uncertain largely because DCs do not produce IL 4. In present investigation, we have uncovered a novel subset of DCs from mice infected with Th2-provoking pathogens Schistosoma japonica, which independently promoted Th2 cells via IL-4-dependent pathway. These DCs contained similar levels of IL-4 mRNA and higher levels of IL-12p40 mRNA comparing to basophils, correlating to their Th2-promoting and Th1-promoting dual polarization capacities. Characterized by expression of FcepsilonRI(+), these DCs were induced independent of T cells. Further investigations revealed that Th2-promoting FcepsilonRI(+) DCs were monocyte-derived inflammatory DCs, which were sufficient to induce Th2 cells in vivo. Egg Ags together with GM-CSF or IL-3 alone were able to stimulate the generation of Th2-promoting FcepsilonRI(+) DCs from bone marrow cells in vitro. To our knowledge, our data for the first time demonstrate that IL 4-producing DCs are induced under some Th2-provoking situations, and they should play important roles in initiation of Th2 response. PMID- 26363055 TI - NK Cells Preferentially Target Tumor Cells with a Cancer Stem Cell Phenotype. AB - Increasing evidence supports the hypothesis that cancer stem cells (CSCs) are resistant to antiproliferative therapies, able to repopulate tumor bulk, and seed metastasis. NK cells are able to target stem cells as shown by their ability to reject allogeneic hematopoietic stem cells but not solid tissue grafts. Using multiple preclinical models, including NK coculture (autologous and allogeneic) with multiple human cancer cell lines and dissociated primary cancer specimens and NK transfer in NSG mice harboring orthotopic pancreatic cancer xenografts, we assessed CSC viability, CSC frequency, expression of death receptor ligands, and tumor burden. We demonstrate that activated NK cells are capable of preferentially killing CSCs identified by multiple CSC markers (CD24(+)/CD44(+), CD133(+), and aldehyde dehydrogenase(bright)) from a wide variety of human cancer cell lines in vitro and dissociated primary cancer specimens ex vivo. We observed comparable effector function of allogeneic and autologous NK cells. We also observed preferential upregulation of NK activation ligands MICA/B, Fas, and DR5 on CSCs. Blocking studies further implicated an NKG2D-dependent mechanism for NK killing of CSCs. Treatment of orthotopic human pancreatic cancer tumor-bearing NSG mice with activated NK cells led to significant reductions in both intratumoral CSCs and tumor burden. Taken together, these data from multiple preclinical models, including a strong reliance on primary human cancer specimens, provide compelling preclinical evidence that activated NK cells preferentially target cancer cells with a CSC phenotype, highlighting the translational potential of NK immunotherapy as part of a combined modality approach for refractory solid malignancies. PMID- 26363057 TI - Cutting Edge: The Orphan Nuclear Receptor Nr4a1 Regulates CD8+ T Cell Expansion and Effector Function through Direct Repression of Irf4. AB - The transcription factor IFN regulatory factor (IRF)4 was shown to play a crucial role in the protective CD8(+) T cell response; however, regulation of IRF4 expression in CD8(+) T cells remains unclear. In this article, we report a critical role for Nr4a1 in regulating the expansion, differentiation, and function of CD8(+) T cells through direct transcriptional repression of Irf4. Without Nr4a1, the regulation of IRF4 is lost, driving an increase in Irf4 expression and, in turn, resulting in a faster rate of CD8 T cell proliferation and expansion. Nr4a1-deficient mice show increases in CD8 T cell effector responses with improved clearance of Listeria monocytogenes. Our data support a novel and critical role for Nr4a1 in the regulation of CD8(+) T cell expansion and effector function through transcriptional repression of Irf4. PMID- 26363058 TI - IL-10 Potentiates Differentiation of Human Induced Regulatory T Cells via STAT3 and Foxo1. AB - Foxp3(+) regulatory T cells (Tregs) play essential roles in maintaining the immune balance. Although the majority of Tregs are formed in the thymus, increasing evidence suggests that induced Tregs (iTregs) may be generated in the periphery from naive cells. However, unlike in the murine system, significant controversy exists regarding the suppressive capacity of these iTregs in humans, especially those generated in vitro in the presence of TGF-beta. Although it is well known that IL-10 is an important mediator of Treg suppression, the action of IL-10 on Tregs themselves is less well characterized. In this article, we show that the presence of IL-10, in addition to TGF-beta, leads to increased expansion of Foxp3(+) iTregs with enhanced CTLA-4 expression and suppressive capability, comparable to that of natural Tregs. This process is dependent on IL-10R-mediated STAT3 signaling, as supported by the lack of an IL-10 effect in patients with IL 10R deficiency and dominant-negative STAT3 mutation. Additionally, IL-10-induced inhibition of Akt phosphorylation and subsequent preservation of Foxo1 function are critical. These results highlight a previously unrecognized function of IL-10 in human iTreg generation, with potential therapeutic implications for the treatment of immune diseases, such as autoimmunity and allergy. PMID- 26363060 TI - Insight Into the Ultrastructure of Antennal Sensilla of Mythimna separata (Lepidoptera: Noctuidae). AB - The oriental armyworm, Mythimna separata (Walk), is one of the most serious pests of cereals in Asia and Australasia. The structure and distribution of the antennal sensilla of M. separata were studied by scanning electron microscopy and transmission electron microscopy. The results showed that antennae of both female and male M. separata are filiform in shape. Three groups and seven morphological sensillum types were recorded in both sexes, including uniporous sensilla (sensilla chaetica), multiporous sensilla (sensilla trichodea, basiconica, coeloconica, and styloconica), and aporous sensilla (sensilla squamiformia and Bohm bristles). S. trichodea, which were the most abundant sensilla, was made of three subtypes (ST I, ST II, and ST III) according to external features and two subtypes of s. basiconica (SB I and SB II) and s. coeloconica (SCo I and SCo II) were identified, respectively. Sexual dimorphisms in sensilla of M. separata were mainly perceived as the variations in the numbers of several sensilla subtypes. Also, the possible functions of the antennal sensilla were discussed. These results contribute to our understanding of the function of antennae in the behavior of M. separata. PMID- 26363059 TI - The Cellular Localization of Human Cytomegalovirus Glycoprotein Expression Greatly Influences the Frequency and Functional Phenotype of Specific CD4+ T Cell Responses. AB - CMV infection is a significant cause of morbidity and mortality in immunocompromised individuals, and the development of a vaccine is of high priority. Glycoprotein B (gB) is a leading vaccine candidate but the glycoprotein H (gH) pentameric complex is now recognized as the major target for neutralizing Abs. However, little is known about the T cell immune response against gH and glycoprotein L (gL) and this is likely to be an important attribute for vaccine immunogenicity. In this study, we examine and contrast the magnitude and phenotype of the T cell immune response against gB, gH, and gL within healthy donors. gB-specific CD4(+) T cells were found in 95% of donors, and 29 epitopes were defined with gB-specific response sizes ranging from 0.02 to 2.88% of the CD4(+) T cell pool. In contrast, only 20% of donors exhibited a T cell response against gH or gL. Additionally, gB-specific CD4(+) T cells exhibited a more cytotoxic phenotype, with high levels of granzyme B expression. Glycoproteins were effectively presented following delivery to APCs but only gB-derived epitopes were presented following endogenous synthesis. gB expression was observed exclusively within vesicular structures colocalizing with HLA-DM whereas gH was distributed evenly throughout the cytoplasm. Grafting of the C-terminal domain from gB onto gH could not transfer this pattern of presentation. These results reveal that gB is a uniquely immunogenic CMV glycoprotein and this is likely to reflect its unique pattern of endogenous Ag presentation. Consideration may be required toward mechanisms that boost cellular immunity to gH and gL within future subunit vaccines. PMID- 26363061 TI - Transovarial Effect of Novaluron on Tribolium castaneum (Coleoptera: Tenebrionidae) After Termination of Direct Contact. AB - The insect growth regulator novaluron (Rimon 10 EC, Makhteshim-Agan Ltd, Israel) is used against many field pests on corn, vegetables, orchards, forests, and cotton plantations. Previously, we studied various effects of novaluron on stored grain pests. Termination in Tribolium castaneum (Herbst) eggs hatching after treating adults with novaluron and following restoration after adult transfer to untreated media was observed. The objective of this study was to investigate the restoration of T. castaneum egg hatch following transfer of adults from treated media to untreated favorable and unfavorable media. The time needed for hatching restoration of 50% of eggs laid by adults transferred from novaluron (1 ppm) treated flour to untreated flour (RT50) was 2.7 d. RT50 for those transferred to untreated wheat grain was 4.1 d. RT90 in flour was 3.6 d, in grain--6.1 d. Varieties of RTs in grain and in flour with nonoverlapping confidence intervals indicate that RTs were significantly different. Delay of eggs hatching restoration for adults transferred from treated flour to unfavorable media (Petri dishes with limited amount of flour, lying of eggs not detected) was observed. RT50 in flour was 2.1 d and RT90--3.1 d, while RT50 in the unfavorable media was 3.4 d and RT90 6.5 d. Delayed effect of egg hatching restoration after adult transfer to unfavorable media provides evidence of the significant role of insect physiological state in novaluron excretion and (or) degradation by T. castaneum females. PMID- 26363063 TI - Fleas and Flea-Associated Bartonella Species in Dogs and Cats from Peru. AB - In the present study, we investigated 238 fleas collected from cats and dogs in three regions of Peru (Ancash, Cajamarca, and Lima) for the presence of Bartonella DNA. Bartonella spp. were detected by amplification of the citrate synthase gene (16.4%) and the 16S-23S intergenic spacer region (20.6%). Bartonella rochalimae was the most common species detected followed by Bartonella clarridgeiae and Bartonella henselae. Our results demonstrate that dogs and cats in Peru are infested with fleas harboring zoonotic Bartonella spp. and these infected fleas could pose a disease risk for humans. PMID- 26363062 TI - Stress kinases in the modulation of metabolism and energy balance. AB - Obesity is a new global pandemic, with growing incidence and prevalence. This disease is associated with increased risk of several pathologies, including diabetes, cardiovascular diseases, and cancer. The mechanisms underlying obesity associated metabolic changes are the focus of efforts to identify new therapies. Stress-activated protein kinases (SAPK), including cJun N-terminal kinases (JNKs) and p38, are required for cellular responses to metabolic stress and therefore might contribute to the pathogenesis of obesity. Tissue-specific knockout models support a cell-type-specific role for JNK isoforms, in particular JNK1, highlighting its importance in cell homeostasis and organ crosstalk. However, more efforts are needed to elucidate the specific roles of other JNK isoforms and p38 family members in metabolism and obesity. This review provides an overview of the role of SAPKs in the regulation of metabolism. PMID- 26363064 TI - A Cell-based Fluorescence Resonance Energy Transfer (FRET) Sensor Reveals Inter- and Intragenogroup Variations in Norovirus Protease Activity and Polyprotein Cleavage. AB - The viral protease represents a key drug target for the development of antiviral therapeutics. Because many protease inhibitors mimic protease substrates, differences in substrate recognition between proteases may affect their sensitivity to a given inhibitor. Here we use a cell-based FRET sensor to investigate the activity of different norovirus proteases upon cleavage of various norovirus cleavage sites inserted into a linker region separating cyan fluorescent protein and yellow fluorescent protein. Using this system, we demonstrate that differences in substrate processing exist between proteases from human noroviruses (genogroups I (GI) and II) and the commonly used murine norovirus (MNV, genogroup V) model. These altered the cleavage efficiency of specific cleavage sites both within and between genogroups. The differences observed between these proteases may affect sensitivity to protease inhibitors and the suitability of MNV as a model system for testing such molecules against the human norovirus protease. Finally, we demonstrate that replacement of MNV polyprotein cleavage sites with the GI or GII equivalents, with the exception of the NS6-7 junction, leads to the production of infectious virus when the MNV NS6 protease, but not the GI or GII proteases, are present. PMID- 26363065 TI - Potassium Bisperoxo(1,10-phenanthroline)oxovanadate (bpV(phen)) Induces Apoptosis and Pyroptosis and Disrupts the P62-HDAC6 Protein Interaction to Suppress the Acetylated Microtubule-dependent Degradation of Autophagosomes. AB - Autophagy is a cellular process that controls and executes the turnover of dysfunctional organelles and misfolded or abnormally aggregated proteins. Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) activates the initiation of autophagy. Autophagosomes migrate along acetylated microtubules to fuse with lysosomes to execute the degradation of the engulfed substrates that usually bind with sequestosome 1 (SQSTM1, p62). Microtubule-associated protein 1 light chain 3 (LC3) traces the autophagy process by converting from the LC3-I to the LC3-II isoform and serves as a major marker of autophagy flux. Potassium bisperoxo(1,10-phenanthroline)oxovanadate (bpV(phen)) is an insulin mimic and a PTEN inhibitor and has the potential to treat different diseases. Here we show that bpV(phen) enhances the ubiquitination of p62, reduces the stability of p62, disrupts the interaction between p62 and histone deacetylase 6 (HDAC6), activates the deacetylase activity of HDAC6 on alpha-tubulin, and impairs stable acetylated microtubules. Microtubular destabilization leads to the blockade of autophagosome lysosome fusion and accumulation of autophagosomes. Autophagy defects lead to oxidative stress and lysosomal rupture, which trigger different types of cell death, including apoptosis and pyroptosis. The consistent results from multiple systems, including mouse and different types of mammalian cells, are different from the predicted function of bpV(phen) as a PTEN inhibitor to activate autophagy flux. In addition, levels of p62 are reduced but not elevated when autophagosomal degradation is blocked, revealing a novel function of p62 in autophagy regulation. Therefore, it is necessary to pay attention to the roles of bpV(phen) in autophagy, apoptosis, and pyroptosis when it is developed as a drug. PMID- 26363066 TI - Novel Insights into Interleukin 6 (IL-6) Cis- and Trans-signaling Pathways by Differentially Manipulating the Assembly of the IL-6 Signaling Complex. AB - The IL-6 signaling complex is described as a hexamer, formed by the association of two IL-6.IL-6 receptor (IL-6R).gp130 trimers, with gp130 being the signal transducer inducing cis- and trans-mediated signaling via a membrane-bound or soluble form of the IL-6R, respectively. 25F10 is an anti-mouse IL-6R mAb that binds to both membrane-bound IL-6R and soluble IL-6R with the unique property of specifically inhibiting trans-mediated signaling events. In this study, epitope mapping revealed that 25F10 interacts at site IIb of IL-6R but allows the binding of IL-6 to the IL-6R and the recruitment of gp130, forming a trimer complex. Binding of 25F10 to IL-6R prevented the formation of the hexameric complex obligate for trans-mediated signaling, suggesting that the cis- and trans-modes of IL-6 signaling adopt different mechanisms for receptor complex assembly. To study this phenomenon also in the human system, we developed NI-1201, a mAb that targets, in the human IL-6R sequence, the epitope recognized by 25F10 for mice. Interestingly, NI-1201, however, did not selectively inhibit human IL-6 trans signaling, although both mAbs produced beneficial outcomes in conditions of exacerbated IL-6 as compared with a site I-directed mAb. These findings shed light on the complexity of IL-6 signaling. First, triggering cis- versus trans mediated IL-6 signaling occurs via distinctive mechanisms for receptor complex assembly in mice. Second, the formation of the receptor complex leading to cis- and trans-signaling biology in mice and humans is different, and this should be taken into account when developing strategies to inhibit IL-6 clinically. PMID- 26363067 TI - EphA2 Receptor Unliganded Dimers Suppress EphA2 Pro-tumorigenic Signaling. AB - The EphA2 receptor tyrosine kinase promotes cell migration and cancer malignancy through a ligand- and kinase-independent distinctive mechanism that has been linked to high Ser-897 phosphorylation and low tyrosine phosphorylation. Here, we demonstrate that EphA2 forms dimers in the plasma membrane of HEK293T cells in the absence of ephrin ligand binding, suggesting that the current seeding mechanism model of EphA2 activation is incomplete. We also characterize a dimerization-deficient EphA2 mutant that shows enhanced ability to promote cell migration, concomitant with increased Ser-897 phosphorylation and decreased tyrosine phosphorylation compared with EphA2 wild type. Our data reveal a correlation between unliganded dimerization and tumorigenic signaling and suggest that EphA2 pro-tumorigenic activity is mediated by the EphA2 monomer. Thus, a therapeutic strategy that aims at the stabilization of EphA2 dimers may be beneficial for the treatment of cancers linked to EphA2 overexpression. PMID- 26363068 TI - Crystal Structure of the Homing Endonuclease I-CvuI Provides a New Template for Genome Modification. AB - Homing endonucleases recognize and generate a DNA double-strand break, which has been used to promote gene targeting. These enzymes recognize long DNA stretches; they are highly sequence-specific enzymes and display a very low frequency of cleavage even in complete genomes. Although a large number of homing endonucleases have been identified, the landscape of possible target sequences is still very limited to cover the complexity of the whole eukaryotic genome. Therefore, the finding and molecular analysis of homing endonucleases identified but not yet characterized may widen the landscape of possible target sequences. The previous characterization of protein-DNA interaction before the engineering of new homing endonucleases is essential for further enzyme modification. Here we report the crystal structure of I-CvuI in complex with its target DNA and with the target DNA of I-CreI, a homologue enzyme widely used in genome engineering. To characterize the enzyme cleavage mechanism, we have solved the I-CvuI DNA structures in the presence of non-catalytic (Ca(2+)) and catalytic ions (Mg(2+)). We have also analyzed the metal dependence of DNA cleavage using Mg(2+) ions at different concentrations ranging from non-cleavable to cleavable concentrations obtained from in vitro cleavage experiments. The structure of I-CvuI homing endonuclease expands the current repertoire for engineering custom specificities, both by itself as a new scaffold alone and in hybrid constructs with other related homing endonucleases or other DNA-binding protein templates. PMID- 26363069 TI - Structural basis for the interaction between the Golgi reassembly-stacking protein GRASP65 and the Golgi matrix protein GM130. AB - GM130 and GRASP65 are Golgi peripheral membrane proteins that play a key role in Golgi stacking and vesicle tethering. However, the molecular details of their interaction and their structural role as a functional unit remain unclear. Here, we present the crystal structure of the PDZ domains of GRASP65 in complex with the GM130 C-terminal peptide at 1.96-A resolution. In contrast to previous findings proposing that GM130 interacts with GRASP65 at the PDZ2 domain only, our crystal structure of the complex indicates that GM130 binds to GRASP65 at two distinct sites concurrently and that both the PDZ1 and PDZ2 domains of GRASP65 participate in this molecular interaction. Mutagenesis experiments support these structural observations and demonstrate that they are required for GRASP65-GM130 association. PMID- 26363070 TI - Single Molecule Imaging Deciphers the Relation between Mobility and Signaling of a Prototypical G Protein-coupled Receptor in Living Cells. AB - Lateral diffusion enables efficient interactions between membrane proteins, leading to signal transmission across the plasma membrane. An open question is how the spatiotemporal distribution of cell surface receptors influences the transmembrane signaling network. Here we addressed this issue by studying the mobility of a prototypical G protein-coupled receptor, the neurokinin-1 receptor, during its different phases of cellular signaling. Attaching a single quantum dot to individual neurokinin-1 receptors enabled us to follow with high spatial and temporal resolution over long time regimes the fate of individual receptors at the plasma membrane. Single receptor trajectories revealed a very heterogeneous mobility distribution pattern with diffusion constants ranging from 0.0005 to 0.1 MUm(2)/s comprising receptors freely diffusing and others confined in 100-600-nm sized membrane domains as well as immobile receptors. A two-dimensional representation of mobility and confinement resolved two major, broadly distributed receptor populations, one showing high mobility and low lateral restriction and the other showing low mobility and high restriction. We found that about 40% of the receptors in the basal state are already confined in membrane domains and are associated with clathrin. After stimulation with an agonist, an additional 30% of receptors became further confined. Using inhibitors of clathrin-mediated endocytosis, we found that the fraction of confined receptors at the basal state depends on the quantity of membrane-associated clathrin and is correlated to a significant decrease of the canonical pathway activity of the receptors. This shows that the high plasticity of receptor mobility is of central importance for receptor homeostasis and fine regulation of receptor activity. PMID- 26363071 TI - Agonism, Antagonism, and Inverse Agonism Bias at the Ghrelin Receptor Signaling. AB - The G protein-coupled receptor GHS-R1a mediates ghrelin-induced growth hormone secretion, food intake, and reward-seeking behaviors. GHS-R1a signals through Gq, Gi/o, G13, and arrestin. Biasing GHS-R1a signaling with specific ligands may lead to the development of more selective drugs to treat obesity or addiction with minimal side effects. To delineate ligand selectivity at GHS-R1a signaling, we analyzed in detail the efficacy of a panel of synthetic ligands activating the different pathways associated with GHS-R1a in HEK293T cells. Besides beta arrestin2 recruitment and ERK1/2 phosphorylation, we monitored activation of a large panel of G protein subtypes using a bioluminescence resonance energy transfer-based assay with G protein-activation biosensors. We first found that unlike full agonists, Gq partial agonists were unable to trigger beta-arrestin2 recruitment and ERK1/2 phosphorylation. Using G protein-activation biosensors, we then demonstrated that ghrelin promoted activation of Gq, Gi1, Gi2, Gi3, Goa, Gob, and G13 but not Gs and G12. Besides, we identified some GHS-R1a ligands that preferentially activated Gq and antagonized ghrelin-mediated Gi/Go activation. Finally, we unambiguously demonstrated that in addition to Gq, GHS-R1a also promoted constitutive activation of G13. Importantly, we identified some ligands that were selective inverse agonists toward Gq but not of G13. This demonstrates that bias at GHS-R1a signaling can occur not only with regard to agonism but also to inverse agonism. Our data, combined with other in vivo studies, may facilitate the design of drugs selectively targeting individual signaling pathways to treat only the therapeutically relevant function. PMID- 26363072 TI - Cardiac RNA induces inflammatory responses in cardiomyocytes and immune cells via Toll-like receptor 7 signaling. AB - We have recently reported that extracellular RNA (exRNA) released from necrotic cells induces cytokine production in cardiomyocytes and immune cells and contributes to myocardial ischemia/reperfusion injury. However, the signaling mechanism by which exRNA exhibits its pro-inflammatory effect is unknown. Here we hypothesize that exRNA directly induces inflammation through specific Toll-like receptors (TLRs). To test the hypothesis, we treated rat neonatal cardiomyocytes, mouse bone marrow-derived macrophages (BMDM), or mouse neutrophils with RNA (2.5 10 MUg/ml) isolated from rat cardiomyocytes or the hearts from mouse, rat, and human. We found that cellular RNA induced production of several cytokines such as macrophage inflammatory protein-2 (MIP-2), ILs, TNFalpha, and the effect was completely diminished by RNase, but not DNase. The RNA-induced cytokine production was partially inhibited in cells treated with TLR7 antagonist or genetically deficient in TLR7. Deletion of myeloid differentiation primary response protein 88 (MyD88), a downstream adapter of TLRs including TLR7, abolished the RNA-induced MIP-2 production. Surprisingly, genetic deletion of TLR3 had no impact on the RNA-induced MIP-2 response. Importantly, extracellular RNA released from damaged cardiomyocytes also induced cytokine production. Finally, mice treated with 50 MUg of RNA intraperitoneal injection exhibited acute peritonitis as evidenced by marked neutrophil and monocyte migration into the peritoneal space. Together, these data demonstrate that exRNA of cardiac origin exhibits a potent pro-inflammatory property in vitro and in vivo and that exRNA induces cytokine production through TLR7-MyD88 signaling. PMID- 26363073 TI - Encephalomyocarditis Virus 3C Protease Relieves TRAF Family Member-associated NF kappaB Activator (TANK) Inhibitory Effect on TRAF6-mediated NF-kappaB Signaling through Cleavage of TANK. AB - TRAF family member-associated NF-kappaB activator (TANK) is a negative regulator of canonical NF-kappaB signaling in the Toll-like receptor- and B-cell receptor mediated signaling pathways. However, functions of TANK in viral infection mediated NF-kappaB activation remain unclear. Here, we reported that TANK was cleaved by encephalomyocarditis virus 3C at the 197 and 291 glutamine residues, which depends on its cysteine protease activity. In addition, encephalomyocarditis virus 3C impaired the ability of TANK to inhibit TRAF6 mediated NF-kappaB signaling. Interestingly, we found that several viral proteases encoded by the foot and mouth disease virus, porcine reproductive and respiratory syndrome virus, and equine arteritis virus also cleaved TANK. Our results suggest that TANK is a novel target of some viral proteases, indicating that some positive RNA viruses have evolved to utilize their major proteases to regulate NF-kappaB activation. PMID- 26363075 TI - Erratum. PMID- 26363081 TI - Is There Still a Survival Advantage to Bypass Surgery Over Percutaneous Intervention in the Modern Era? AB - The method of revascularization for multi-vessel coronary artery disease (MVD) has traditionally been coronary artery bypass grafting (CABG), however, due to recent advances in the field of percutaneous coronary intervention (PCI), this latter technique has gained in popularity and its role in guidelines has been promoted. This review aims to address the current data available for the treatment of patients with complex coronary disease, including the specific disease subset in those with diabetes mellitus, focusing on the importance of risk stratification and review by the 'Heart Team'. The concept of complete versus incomplete revascularization and the assessment of lesions utilizing functional techniques are discussed. Over recent years, PCI has grown to become the most frequently performed therapeutic intervention in medicine and continues to grow. There are encouraging data that this is an effective and safe treatment option in selected patients, however, neither strategy alone can provide a solution for the entire spectrum of patients with MVD. PMID- 26363082 TI - Reconstructing the hidden states in time course data of stochastic models. AB - Parameter estimation is central for analyzing models in Systems Biology. The relevance of stochastic modeling in the field is increasing. Therefore, the need for tailored parameter estimation techniques is increasing as well. Challenges for parameter estimation are partial observability, measurement noise, and the computational complexity arising from the dimension of the parameter space. This article extends the multiple shooting for stochastic systems' method, developed for inference in intrinsic stochastic systems. The treatment of extrinsic noise and the estimation of the unobserved states is improved, by taking into account the correlation between unobserved and observed species. This article demonstrates the power of the method on different scenarios of a Lotka-Volterra model, including cases in which the prey population dies out or explodes, and a Calcium oscillation system. Besides showing how the new extension improves the accuracy of the parameter estimates, this article analyzes the accuracy of the state estimates. In contrast to previous approaches, the new approach is well able to estimate states and parameters for all the scenarios. As it does not need stochastic simulations, it is of the same order of speed as conventional least squares parameter estimation methods with respect to computational time. PMID- 26363074 TI - Substrate-induced unlocking of the inner gate determines the catalytic efficiency of a neurotransmitter:sodium symporter. AB - Neurotransmitter:sodium symporters (NSSs) mediate reuptake of neurotransmitters from the synaptic cleft and are targets for several therapeutics and psychostimulants. The prokaryotic NSS homologue, LeuT, represents a principal structural model for Na(+)-coupled transport catalyzed by these proteins. Here, we used site-directed fluorescence quenching spectroscopy to identify in LeuT a substrate-induced conformational rearrangement at the inner gate conceivably leading to formation of a structural intermediate preceding transition to the inward-open conformation. The substrate-induced, Na(+)-dependent change required an intact primary substrate-binding site and involved increased water exposure of the cytoplasmic end of transmembrane segment 5. The findings were supported by simulations predicting disruption of an intracellular interaction network leading to a discrete rotation of transmembrane segment 5 and the adjacent intracellular loop 2. The magnitude of the spectroscopic response correlated inversely with the transport rate for different substrates, suggesting that stability of the intermediate represents an unrecognized rate-limiting barrier in the NSS transport mechanism. PMID- 26363083 TI - Chemical reaction network approaches to Biochemical Systems Theory. AB - This paper provides a framework to represent a Biochemical Systems Theory (BST) model (in either GMA or S-system form) as a chemical reaction network with power law kinetics. Using this representation, some basic properties and the application of recent results of Chemical Reaction Network Theory regarding steady states of such systems are shown. In particular, Injectivity Theory, including network concordance [36] and the Jacobian Determinant Criterion [43], a "Lifting Theorem" for steady states [26] and the comprehensive results of Muller and Regensburger [31] on complex balanced equilibria are discussed. A partial extension of a recent Emulation Theorem of Cardelli for mass action systems [3] is derived for a subclass of power law kinetic systems. However, it is also shown that the GMA and S-system models of human purine metabolism [10] do not display the reactant-determined kinetics assumed by Muller and Regensburger and hence only a subset of BST models can be handled with their approach. Moreover, since the reaction networks underlying many BST models are not weakly reversible, results for non-complex balanced equilibria are also needed. PMID- 26363084 TI - Drosophila type IV collagen mutation associates with immune system activation and intestinal dysfunction. AB - The basal lamina (BM) contains numerous components with a predominance of type IV collagens. Clinical manifestations associated with mutations of the human COL4A1 gene include perinatal cerebral hemorrhage and porencephaly, hereditary angiopathy, nephropathy, aneurysms and muscle cramps (HANAC), ocular dysgenesis, myopathy, Walker-Warburg syndrome and systemic tissue degeneration. In Drosophila, the phenotype associated with dominant temperature sensitive mutations of col4a1 include severe myopathy resulting from massive degradation of striated muscle fibers, and in the gut, degeneration of circular visceral muscle cells and epithelial cells following detachment from the BM. In order to determine the consequences of altered BMfunctions due to aberrant COL4A1 protein, we have carried out a series of tests using Drosophila DTS-L3 mutants from our allelic series of col4a1 mutations with confirmed degeneration of various cell types and lowest survival rate among the col4a1 mutant lines at restrictive temperature. Results demonstrated epithelial cell degeneration in the gut, shortened gut, enlarged midgut with multiple diverticulae, intestinal dysfunction and shortened life span. Midgut immunohistochemistry analyses confirmed altered expression and distribution of BM components integrin PSI and PSII alpha subunits, laminin gamma 1, and COL4A1 both in larvae and adults. Global gene expression analysis revealed activation of the effector AMP genes of the primary innate immune system including Metchnikowin, Diptericin, Diptericin B, and edin that preceded morphological changes. Attacin::GFP midgut expression pattern further supported these changes. An increase in ROS production and changes in gut bacterial flora were also noted and may have further enhanced an immune response. The phenotypic features of Drosophila col4a1 mutants confirmed an essential role for type IV collagen in maintaining epithelial integrity, gut morphology and intestinal function and suggest that aberrant structure and function of the COL4A1 protein may also be a significant factor in modulating immunity. PMID- 26363085 TI - DNA vaccination boosts Bacillus Calmette-Guerin protection against mycobacterial infection in zebrafish. AB - Despite the widespread use of the current Bacillus Calmette-Guerin (BCG) vaccine, tuberculosis is still a major cause of morbidity and mortality worldwide. Vaccination with BCG does not prevent a Mycobacterium tuberculosis infection, nor does it inhibit the reactivation of latent tuberculosis. Here, we show that adult zebrafish are modestly and variably protected from a mycobacterial infection by BCG vaccination. An intraperitoneal (i.p.) BCG vaccination was associated with enhanced survival upon a high-dose (20,000 bacteria) Mycobacterium marinum infection. In addition, BCG-vaccinated fish were more able to restrict a low-dose (30 bacteria) intraperitoneal infection with M. marinum, as indicated by lower bacterial loads at six weeks post infection (wpi). However, the vaccination could not completely prevent an infection. A qRT-PCR analysis comparing BCG-vaccinated and unvaccinated fish upon a mycobacterial infection indicated that the induction of Tumor necrosis factor (TNF) was more modest in vaccinated fish. The partial protection gained by BCG could be boosted by a DNA vaccine combining Ag85B, ESAT6 and a resuscitation-related gene RpfE, suggesting that this combination of antigens could be useful for a future BCG booster vaccine. We conclude that zebrafish is a useful early-phase preclinical model for studying subunit vaccines designed for boosting the effects of BCG. PMID- 26363086 TI - Nemo like kinase negatively regulates NF-kappaB activation and coelomocytes apoptosis in Apostichopus japonicus. AB - Nuclear factor kappa B (NF-kappaB) transcription factors are related to several physiological processes, including innate and acquired immunity. In this study, a novel negative regulator of the Nemo-like kinase (NLK) gene was identified from Apostichopus japonicus through PCR (denoted as AjNLK). The complete AjNLK cDNA was of 2335 bp, with a 5'-UTR of 315 bp, a 3'-UTR of 718 bp, and a putative ORF of 1302 bp, and encoded a polypeptide of 433 amino acid residues with a typical serine/threonine protein kinase domain. Blast analysis revealed that AjNLK shared a high degree of structural conservation with its counterparts from other invertebrates and vertebrates. Spatial expression analysis indicated that the expression of AjNLK mRNA transcripts was higher in the tentacles than that in coelomocytes. The expression of AjNLK mRNA in coelomocytes was suppressed after Vibrio splendidus challenge by 0.51-fold and 0.41-fold at 72 and 96 h, respectively, compared with that in the control group. Similarly, AjNLK expression was down-regulated in primary coelomocytes exposed to 1 MUg mL(-1) lipopolysaccharide (LPS). Functional investigation further revealed that the NF kappaB factor p105 was induced at both mRNA and protein levels after AjNLK silencing in vitro. Meanwhile, the apoptosis of LPS-induced coelomocytes was significantly inhibited in AjNLK siRNA-transfected coelomocytes. These results supported that AjNLK negatively regulated NF-kappaB activation and cell apoptosis in sea cucumber. PMID- 26363087 TI - Megasonic sonication for cost-effective and automatable elution of Cryptosporidium from filters and membranes. AB - Sample processing is a highly challenging stage in the monitoring of waterborne pathogens. This step is time-consuming, requires highly trained technicians and often results in low recovery rates of pathogens. In the UK but also in other parts of the world, Cryptosporidium is the only pathogen directly tested for in routine operational monitoring. The traditional sampling process involves the filtration of 1000L of water, semi-automated elution of the filters and membranes with recovery rates of about 30-40% typically. This paper explores the use of megasonic sonication in an attempt to increase recovery rates and reduce both the time required for processing and the number of labour-intensive steps. Results demonstrate that megasonic energy assisted elution is equally effective as the traditional manual process in terms of recovery rates. Major advantages are however offered in terms of reduction of the elution volume enabling the current centrifugation stage to be avoided. This saves time, equipment and staff costs and critically removes the step in the process that would be most challenging to automate, paving the way thereby for highly effective automated solutions to pathogens monitoring. PMID- 26363088 TI - The willingness to pay of parties to traffic accidents for loss of productivity and consolation compensation. AB - In this study, willingness to pay (WTP) for loss of productivity and consolation compensation by parties to traffic accidents is investigated using the Tobit model. In addition, WTP is compared to compensation determined by Taiwanese courts. The modelling results showed that variables such as education, average individual monthly income, traffic accident history, past experience of severe traffic accident injuries, the number of working days lost due to a traffic accident, past experience of accepting compensation for traffic accident-caused productivity loss and past experience of accepting consolation compensation caused by traffic accidents have a positive impact on WTP. In addition, average WTP for these two accident costs were obtained. We found that parties to traffic accidents were willing to pay more than 90% of the compensation determined by the court in the scenario of minor and moderate injuries. Parties were willing to pay approximately 80% of the compensation determined by the court for severe injuries, disability and fatality. Therefore, related agencies can use our study findings as the basis for determining the compensation that parties should pay for productivity losses caused by traffic accidents of different types. PMID- 26363090 TI - Sodium thiosulfate protects brain in rat model of adenine induced vascular calcification. AB - Vascular bed calcification is a common feature of ends stage renal disease that may lead to a complication in cardiovascular and cerebrovascular beds, which is a promoting cause of myocardial infarction, stroke, dementia and aneurysms. Sodium thiosulfate (STS) due to its multiple properties such as antioxidant and calcium chelation has been reported to prevent vascular calcification in uremic rats, without mentioning its impact on cerebral function. Moreover, the previous studies have not explored the effect of STS on the mitochondrial dysfunction, one of the main pathophysiological features associated with the disease and the main site for STS metabolism. The present study addresses this limitation by using a rat model where 0.75% adenine was administered to induce vascular calcification and 400 mg/kg b wt. of STS was given as preventive and curative agent. The blood and urine chemistries along with histopathology of aorta confirms the renal protective effect of STS in two modes of administration. The brain oxidative stress assessment was made through TBARS level, catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities, found to be in the near normal level. STS administration not only reduced the mitochondrial oxidative stress (measured by TBARS, SOD, GPx and CAT) but also preserved the mitochondrial respiratory enzyme activities (NADH dehydrogenase, Succinate dehydrogenase and Malate dehydrogenase) and its physiology (measured by P/O ratio and RCR). In fact, the protective effect of STS was prominent, when it was administered as a curative agent, where low H2S and high thiosulfate level was observed along with low cystathionine beta synthase activity, confirms thiosulfate mediated renal protection. In conclusion, STS when given after induction of calcification is protective to the brain by preserving its mitochondria, compared to the treatment given concomitantly. PMID- 26363091 TI - Relationship Between Reverse Remodeling and Cardiopulmonary Exercise Capacity in Heart Failure Patients Undergoing Cardiac Resynchronization Therapy. AB - BACKGROUND: Studies on the relationship between left ventricular reverse remodeling and cardiopulmonary exercise capacity in heart failure patients undergoing cardiac resynchronization therapy (CRT) are scarce and inconclusive. METHODS AND RESULTS: Eighty-four patients with a 1st-time CRT-defibrillator (mean age 65 +/- 11; 73% male) underwent echocardiography and cardiopulmonary exercise testing (CPX) before implantation (baseline) and 6 months after implantation. At baseline, patients also completed a set of questionnaires measuring mental and physical health. The association between echocardiographic response (left ventricular end-systolic volume decrease >=15%) and a comprehensive set of CPX results was examined. Echocardiographic responders (54%) demonstrated higher peak oxygen consumption and better exercise performance than nonresponders at baseline and at 6-month follow-up. Furthermore, only echocardiographic responders showed improvements in ventilatory efficiency during follow-up. Multivariable repeated measures analyses revealed that, besides reverse remodeling, New York Heart Association functional class II and good patient-reported health status before implantation were the most important correlates of higher average oxygen consumption during exercise, and that nonischemic etiology and smaller pre implantation QRS width were associated with better ventilatory efficiency over time. CONCLUSIONS: During the first 6 months of CRT there was a significant positive association between reverse remodeling and cardiopulmonary exercise capacity. PMID- 26363089 TI - Micro- and nanodevices integrated with biomolecular probes. AB - Understanding how biomolecules, proteins and cells interact with their surroundings and other biological entities has become the fundamental design criterion for most biomedical micro- and nanodevices. Advances in biology, medicine, and nanofabrication technologies complement each other and allow us to engineer new tools based on biomolecules utilized as probes. Engineered micro/nanosystems and biomolecules in nature have remarkably robust compatibility in terms of function, size, and physical properties. This article presents the state of the art in micro- and nanoscale devices designed and fabricated with biomolecular probes as their vital constituents. General design and fabrication concepts are presented and three major platform technologies are highlighted: microcantilevers, micro/nanopillars, and microfluidics. Overview of each technology, typical fabrication details, and application areas are presented by emphasizing significant achievements, current challenges, and future opportunities. PMID- 26363092 TI - Dopamine signaling regulates the projection patterns in the mouse chiasm. AB - Ocular albinism (OA) is characterized by inadequate L-3, 4-dihydroxyphenylalanine (L-DOPA) and dopamine (DA) in the eyes. This study investigated DA-related signaling pathways in mouse chiasm projection patterns and the potential role of ocular albinism type 1 (OA1) and dopamine 1A (D1A) receptors in the optic pathway. In embryonic day (E) E13-E15 retina, most L-DOPA and OA1-positive cells were distributed among Muller glial cells on E13 and retinal ganglion cells (RGC) on E14. In the ventral diencephalon, OA1 and L-DOPA were strongly expressed on the optic chiasm (OC) and optic tract (OT), respectively, but weak on the optic stalk (OS). At E13-E15, DA and D1A staining was predominately expressed in radially arranged cells with a neuronal expression pattern. In the ventral diencephalon, DA and D1A were strongly expressed on the OC, OT and OS. Furthermore, L-DOPA significantly inhibited retinal axon outgrowth in both the dorsal nasal (DN) and ventral temporal (VT) groups. DA inhibited retinal axon outgrowth, which was abolished by the D1A antagonist SCH23390. Brain slice cultures indicated that L-DOPA inhibited axons that crossed at the OC of E13 embryos, which was not abolished by DA. L-DOPA also inhibited axons that crossed at the OC of albino mice. Albino mice exhibited reduced ipsilateral retinal projections compared with C57 pigmented mice. No significant difference was identified in the uncrossed projections of albino mice following L-DOPA and DA expression. Furthermore, transcription factor Zic family member 2 (Zic2) upregulated OA1 mRNA expression. Our findings provide critical insights into DA related signaling in retinal development. PMID- 26363093 TI - Vasoactive intestinal peptide administration after stroke in rats enhances neurogenesis and improves neurological function. AB - The aim of this study was to investigate the effects of vasoactive intestinal peptide (VIP) on neurogenesis and neurological function after cerebral ischemia. Rats were intracerebroventricular administered with VIP after a 2h middle cerebral artery occlusion (MCAO) and sacrificed at 7, 14 and 28 days after MCAO. Functional outcome was studied with the modified neurological severity score. The infarct volume was evaluated via histology. Neurogenesis, angiogenesis and the protein expression of vascular endothelial growth factor (VEGF) were measured by immunohistochemistry and Western blotting analysis, respectively. The treatment with VIP significantly reduced the neurological severity score and the infarc volume, and increased the numbers of bromodeoxyuridine (BrdU) immunoreactive cells and doublecortin immunoreactive area in the subventricular zone (SVZ) at 7, 14 and 28 days after ischemia. The cerebral protein levels of VEGF and VEGF expression in the SVZ were also enhanced in VIP-treated rats at 7 days after stroke. VIP treatment obviously increased the number of BrdU positive endothelial cells in the SVZ and density of cerebral microvessels in the ischemic boundary at 28 days after ischemia. Our study suggests that in the ischemic rat brain VIP reduces brain damage and promotes neurogenesis by increasing VEGF. VIP-enhanced neurogenesis is associated with angiogenesis. These changes may contribute to improvement in functional outcome. PMID- 26363095 TI - Bladder Mass in Newborn: Case Report and Review of Literature. AB - Benign proliferative lesions of the bladder are exceptional in neonates. We describe a case of a 3-day-old neonate, presenting with bloody meconium and sonographic diagnosis of bladder mass. Cystoscopic biopsies were performed and a diagnosis of polypoid cystitis was made. The patient was treated conservatively and the lesion healed during follow-up. We review the literature of other cases of neonatal bladder masses. PMID- 26363096 TI - Investigation of biochemical changes of the ovine calpain 3 exon-10 polymorphism. AB - Calpain 3 (CAPN3) is a tissue specific calpain, and its mRNA is the most expressed calpain isoform in skeletal muscles. Many mutations and polymorphisms within the human CAPN3 gene have been reported and related to limb-girdle muscular dystrophy. Several reports link CAPN3 polymorphisms and meat quality. An association between three allele variants in exon-10 of ovine CAPN3 and the yield of fat trimmed meat cuts has been reported. This research investigated the biochemical significance of polymorphic variation in CAPN3. CAPN3 mRNA sequences were obtained from muscle samples collected from lambs which were homozygous for each of the three alleles. Four single base substitutions were found besides those in exon-10, but none of them, including the variations within exon-10, caused a change in amino acid sequence. The expression of CAPN3 mRNA and the amounts of CAPN3 protein were also compared among genotypes, and no significant differences were found. These results suggest that the reported association of specific allele variants within CAPN3 exon-10 to phenotype variations were not direct effects of CAPN3 polymorphisms. Interspecies analyses of the CAPN3 sequences indicated that the sequence reported here is more likely to be the correct common ovine CAPN3 sequence than the reference sequence. PMID- 26363094 TI - Hyperactivity and depression-like traits in Bax KO mice. AB - The Bax gene is a member of the Bcl-2 gene family and its pro-apoptotic Bcl associated X (Bax) protein is believed to be crucial in regulating apoptosis during neuronal development as well as following injury. With the advent of mouse genomics, mice lacking the pro-apoptotic Bax gene (Bax KO) have been extensively used to study how cell death helps to determine synaptic circuitry formation during neurodevelopment and disease. Surprisingly, in spite of its wide use and the association of programmed neuronal death with motor dysfunctions and depression, the effects of Bax deletion on mice spontaneous locomotor activity and depression-like traits are unknown. Here we examine the behavioral characteristics of Bax KO male mice using classical paradigms to evaluate spontaneous locomotor activity and depressive-like responses. In the open field, Bax KO animals exhibited greater locomotor activity than their control littermates. In the forced swimming test, Bax KO mice displayed greater immobility times, a behavior despair state, when compared to controls. Collectively, our findings corroborate the notion that a fine balance between cell survival and death early during development is critical for normal brain function later in life. Furthermore, it points out the importance of considering depressive-like and hyperactivity behavioral phenotypes when conducting neurodevelopmental and other studies using the Bax KO strain. PMID- 26363097 TI - Down-regulated expression of miR-134 contributes to paclitaxel resistance in human ovarian cancer cells. AB - MiR-134 has been reported to have a role in the development and progression of various cancers. In this study, we found that miR-134 expression was significantly decreased in chemo-resistant serous epithelial ovarian cancer (EOC) patients. Over-expression of miR-134 enhanced the sensitivity of SKOV3-TR30 cells to paclitaxel, and increased paclitaxel-induced apoptosis. Further, Pak2 was identified as a direct target of miR-134, and Pak2-specific siRNA increased cell inhibition rate and promoted paclitaxal-induced apoptosis. By regulating Pak2 expression, miR-134 could mediate Bad phosphorylation at Ser112 and Ser136, which affected cell survival and apoptosis. In conclusion, our findings indicate that repression of miR-134 and consequent up-regulation of Pak2 might contribute to paclitaxel resistance. PMID- 26363099 TI - An eccentric calpain, CAPN3/p94/calpain-3. AB - Calpains are Ca(2+)-regulated proteolytic enzymes that are involved in a variety of biological phenomena. Calpains process substrates by limited proteolysis to modulate various protein functions in the cell, and are thus called "modulator proteases." CAPN3, previously called p94 or calpain-3, has unique features that are not found in any of the other 14 human calpains, or even in other proteases. For instance, CAPN3 undergoes extremely rapid and exhaustive autodegradation. CAPN3 is also the first (and so far, the only) intracellular enzyme found to depend on Na(+) for its activation. CAPN3 has both proteolytic and non proteolytic functions. It has the interesting distinction of being the only protease, other than a few virus proteases, with the ability to regain protease function after its autolytic dissociation; this occurs through a process known as intermolecular complementation (iMOC). Gene mutations causing CAPN3 defects are responsible for limb-girdle muscular dystrophy type 2A (LGMD2A). Unusual characteristics of CAPN3 have fascinated researchers, but have also hampered conventional biochemical analysis. In this review, we describe significant findings about CAPN3 from its discovery to the present, and suggest promising avenues for future CAPN3 research. PMID- 26363098 TI - Growth phase-dependent composition of the Helicobacter pylori exoproteome. AB - Helicobacter pylori colonizes the human stomach and is associated with an increased risk of gastric cancer and peptic ulcer disease. Analysis of H. pylori protein secretion is complicated by the occurrence of bacterial autolysis. In this study, we analyzed the exoproteome of H. pylori at multiple phases of bacterial growth and identified 74 proteins that are selectively released into the extracellular space. These include proteins known to cause alterations in host cells, antigenic proteins, and additional proteins that have not yet been studied in any detail. The composition of the H. pylori exoproteome is dependent on the phase of bacterial growth. For example, the proportional abundance of the vacuolating toxin VacA in culture supernatant is higher during late growth phases than early growth phases, whereas the proportional abundance of many other proteins is higher during early growth phases. We detected marked variation in the subcellular localization of putative secreted proteins within soluble and membrane fractions derived from intact bacteria. By providing a comprehensive view of the H. pylori exoproteome, these results provide new insights into the array of secreted H. pylori proteins that may cause alterations in the gastric environment. PMID- 26363100 TI - Anticancer molecule AS1411 exhibits low nanomolar antiviral activity against HIV 1. AB - During clinical trials, a number of fully characterized molecules are dropped along the way because they do not provide enough benefit for the patient. Some of them show limited side effects and might be of great use for other applications. AS1411 is a nucleolin-targeting aptamer that underwent phase II clinical trials as anticancer agent. Here, we show that AS1411 exhibits extremely potent antiviral activity and is therefore an attractive new lead as anti-HIV agent. PMID- 26363101 TI - The role of dietary acid load and mild metabolic acidosis in insulin resistance in humans. AB - Type 2 diabetes is increasingly being recognised as a global health crisis (World Health Organisation). Insulin resistance is closely associated with obesity and precedes the development of type 2 diabetes. However, there is now increasing evidence to suggest that diet itself may independently be associated with type 2 diabetes risk. A diet with a high acid load (or high potential renal net acid load, PRAL) can result in a decrease in pH towards the lower end of the normal physiological range, which may in turn lead to the development of insulin resistance. Conversely, reducing dietary acid load (the so called 'alkaline diet') may be protective and prevent the onset of type 2 diabetes. Here, we explore the influence of dietary acid load on the development of mild metabolic acidosis and induction of insulin resistance. Whilst large prospective cohort studies link high dietary acid load or low serum bicarbonate with the development of type 2 diabetes, the effect of a diet with a low acid (or high alkaline) load remains unclear. Further interventional studies are required to investigate the influence of dietary composition on the body's acid/base balance, insulin resistance and incidence of type 2 diabetes. PMID- 26363102 TI - The size of the primary cilium and acetylated tubulin are modulated during adipocyte differentiation: Analysis of HDAC6 functions in these processes. AB - The primary cilium is an organelle present in most of the cells of the organism. Ciliopathies, such as the Bardet Biedl and the Alstrom syndromes are associated with obesity. We, and others, have shown that the primary cilium undergoes size modifications during adipocyte differentiation of human adipose stromal cells. We show here that the levels of acetylated alpha-tubulin, a constituent of the primary cilium, and the expression of HDAC6, the enzyme that deacetylates alpha tubulin and is responsible for the loss of the cilium during mitosis, are modulated during adipogenesis. Moreover, during adipocyte differentiation cells that express higher level of HDAC6 are the first to lose their primary cilium. We have investigated the function of HDAC6 on adipocyte differentiation and on the primary cilium. We observe that inhibition of HDAC6 activity leads to a decrease in adipocyte differentiation. This is associated with an inhibition of the initial elongation of the cilium. Interestingly, overexpression of HDAC6 inhibits adipocyte differentiation and blunts the elongation of the primary cilium. In both situations, inhibition of adipocyte differentiation was not associated with an inhibition of the glucocorticoid receptor activity. This indicates that HDAC6 controls adipogenesis through the levels of acetylated alpha-tubulin. Moreover, we show that although HDAC6 expression increases during adipocyte differentiation it is not sufficient to provoke the loss of the cilium. This suggests the existence of a novel mechanism for the loss of the cilium. Together, these data indicate that HDAC6, and acetylated alpha-tubulin, are important regulator of adipocyte differentiation. PMID- 26363103 TI - Urinary myoglobin quantification by high-performance liquid chromatography: An alternative measurement for exercise-induced muscle damage. AB - This study investigated a means of quantifying urinary myoglobin using a novel reverse-phase high-performance liquid chromatography (RP-HPLC) method that is an alternative measure of exercise-induced muscle damage. It also investigated the effect of storage and alkalization on urinary myoglobin stability issues. An RP HPLC method was validated by precision and repeatability experiments. Myoglobin stability was determined through spiked urine samples stored at various temperatures over an 8-week period using alkalization and dilution in a pH 7.0 buffer. The method was validated with urine collected from mixed martial arts fighters during a competition and training session. The method produced linearity from 5 to 1000 MUg/ml (R(2) = 0.997), intra- and inter-assay coefficients of variation from 0.32 to 2.94%, and a lower detection limit of 0.2 MUg/ml in the final dilution and 2 MUg/ml in the original urine sample. Recovery ranged from 96.4 to 102.5%, myoglobin remained stable at 4 degrees C when diluted in a pH 7.0 buffer after 20 h, and a significant increase (P < 0.01) and an identifiable peak were observed following a mixed martial arts contest and training session. Storage length and conditions had significant effects (P < 0.05) on stability. The method's simplicity and noninvasive nature means it can be used as an alternative muscle damage assay following exercise and trauma. PMID- 26363104 TI - Large abdominoscrotal hydrocele: Uncommon surgical entity. AB - INTRODUCTION: An abdominoscrotal hydrocele (ASH) consists of a large inguinoscrotal hydrocele which communicates in an hour glass fashion with a large "intraabdominal component". Mostly affects single testis but very rarely can present bilaterally. PRESENTATION OF CASE: We are presenting here a young 25 year old patient with large right sided scrotal swelling encroaching over lower abdomen. Clinically it was abdominoscrotal hydrocele which was confirmed with CT abdomen and later on subjected for surgery. DISCUSSION: Abdominoscrotal hydrocele is rarest type of hydrocele; first described by Dupuytren. The etiology of ASH is unknown; however, different theories have been described in literature to explain the pathogenesis. Diagnosis of ASH is done by clinical examination and is confirmed by radiological examination. Though ultrasonography is the first choice, in few selected cases contrast enhanced computerized tomography or magnetic resonant imaging may be helpful for more anatomical delineation. It may present with various complications secondary to pressure exerted by the components of the ASH. Surgical excision of the sac is the only definitive treatment option. There is no role of conservative treatment. Sometimes, decompression of the cyst needed to ease the dissection of the sac. CONCLUSION: Abdominoscrotal hydrocele differential should be considered while dealing with large lower abdominal swelling along with scrotal swelling. PMID- 26363105 TI - Perforated Meckel's diverticulum in an adult due to faecolith: A case report and review of literature. AB - Meckel's diverticulum (MD) is a persistent remnant of the vitelointestinal duct and is present in 2% of population [1]. It is the most common congenital malformation of the gastrointestinal tract. It can present clinically as haemorrhage, diverticulitis, intussusception, chronic ulceration, intestinal obstruction and perforation. Complicated presentation, especially bleeding, tends to be more common in the paediatric group, whereas intestinal obstruction is more common in adults [2]. Patients with a perforation of Meckel's diverticulum by an enterolith are rare and may present with right iliac fossa pain, which mimics acute appendicitis. PMID- 26363106 TI - Cytomegalovirus enteritis with ischemia in an immunocompetent patient: A rare case report. AB - INTRODUCTION: Cytomegalovirus (CMV) is predominantly an opportunistic infection in the immunocompromised patients. Though, there are few cases of CMV colitis being reported in the immunocompetent individuals, CMV enteritis is exceedingly rare and enteritis leading into small bowel ischemia has never been reported yet. PRESENTATION OF CASE: A-78-year-old male patient presented with distal small obstruction for 4 days duration. Clinical examination revealed a distended abdomen and localised peritonism in right iliac fossa. An initial computed tomography (CT) scan revealed distended small bowel loops up to the thickened inflammed terminal illeum with no free fluid or gas and a normal appendix. No immunosuppressive risk factors such as human immunodeficiency virus, transplant procedures, or steroid therapy were present. Hematologic investigations showed leucocytosis with neutrophilia. Diagnostic laparoscopy confirmed a thickened terminal ileum causing small bowel obstruction. Laparoscopy converted to laparotomy and right hemicolectomy was performed. Histology showed isolated small bowel ischemia with ulcerative changes and cytomegalovirus inclusions. The patient was started on ganciclovir therapy and subsequently had an uneventful recovery and discharged after 16 days. DISCUSSION: Cytomegalovirus enteritis was initially not suspected in our patient. In this case CMV caused ischemia of the small bowel without evidence of colonic involvement. Even in elderly patients, the small bowel remains resilient to the ischemic changes because of the copious blood supply. CONCLUSION: We report possibly the first case of isolated small bowel ischaemia caused by cytomegalovirus in immunocompetent individuals, needed surgical resection. PMID- 26363107 TI - Positivity and incidence of human papillomavirus in women attending gynecological department of a major comprehensive hospital in Kunming, China 2012-2014. AB - HPV DNA testing is receiving increasing popularity in cervical cancer screening. There is a lack of universal guidelines on HPV testing. Our study aimed to assess age-specific and year-on-year trend of HPV positivity and incidence and HPV retesting among 26,457 individual women attending the gynecological department at the First People's Hospital of Yunnan Province (FPHY) who had an HPV testing between January 1, 2012 and December 31, 2014. HPV 16, HPV 52, and cp8304 ranked among top 5 with regard to positivity in each year and overall incidence. The positivity of various HPV types peaked among women aged 15-19 years, then sharply decreased with age, stabilized among women aged 25-49 years and then surged again among women aged 50 years and older. The positivity of high-risk (HR) HPV types, including HPV 16, 18, 31, 33, 56 and 58, were on the rise during the time period (P < 0.05 for all). HR HPV types tended to be more likely to persist than LR HPV types (P < 0.05). Additionally, the incidence rate for any HR HPV type was also significantly higher than that for any LR HPV type (42.8 vs. 12.6 per 100 person years, P < 0.001). The majority (57.3-77.5%) of women detected with HR HPV types did not retest within 12 months. Clinical guidelines on HPV DNA testing are needed and education, and counseling about HPV infection and its implications for women detected with HPV at clinical settings, are warranted. PMID- 26363108 TI - Compaction behavior and deformation mechanism of directly compressible textured mannitol in a rotary tablet press simulator. AB - Textured mannitol powder is widely used as a pharmaceutical excipient for tablet compaction. In order to choose the right tableting parameters, it is necessary to understand its mechanical behavior during deformation under industrial tableting conditions. The aim of this study was to evaluate the mechanical behavior during deformation of a textured mannitol using a rotary tablet press simulator. Mean yield pressure (Py) obtained by Heckel modeling, Walker coefficients (W) and Stress Rate Sensitivity (SRS) were compared to reference excipients, known for either their plastic (microcrystalline cellulose) or fragmentary (lactose and dibasic calcium phosphate) deformation behavior. Py, W and SRS values showed that the studied textured mannitol has a fragmentary deformation mechanism. Furthermore, this mechanical behavior was not sensitive to lubrication, which is characteristic of fragmentary excipients. PMID- 26363109 TI - The bending strength of tablets with a breaking line--Comparison of the results of an elastic and a "brittle cracking" finite element model with experimental findings. AB - The aim of this work was to ascertain the influence of the position of the breaking line of bevel-edged tablets in a three-point bending test. Two different brands of commercially available, flat-round, bevel-edged tablets with a single central breaking line were studied. Breaking line positions tested, relative to the upper loading roll, were 0 degrees , 22.5 degrees , 45 degrees , 67.5 degrees and 90 degrees . The breaking line faced either up- or downwards during the test. The practical results were compared with FEM results simulating similar test configurations. Tablets failed mainly across the failure plane, resulting in two tablet halves. An exception to this was found for tablets where the breaking line faced down and was positioned at an angle of 22.5 degrees relative to the loading plane. Here the crack followed the breaking line in the centre of the tablets and only diverged towards the loading plane position at the edges of the tablets. The breaking line facing upwards resulted in a significantly higher tensile strength of the tablets compared to it facing downwards. However, with one exception, the orientation of the breaking line relative to the loading plane appeared not to affect the tensile strength values. A fully elastic FEM model indicated that both the position of the breaking line relative to the loading plane and as to whether the breaking line faced up- or downwards during the bending test would result in considerably different failure loads during practical experiments. The results also suggested that regardless of the breaking line position, when it is facing down crack propagation should start at the outer edges propagating towards the midpoint of the discs until failure occurs. Failure should hence always result in equal tablet halves, whereby the failure plane should coincide with the loading plane. Neither predictions fully reflected the practical behaviour of the tablets. Using a brittle cracking FEM model significantly larger tensile stresses for tablets with the breaking line positioned downwards at 0 degrees or 22.5 degrees relative to the loading plane were still predicted, but the differences between model and experimental values was greatly reduced. The remaining differences are more likely due to the inadequacy of the equation available to calculate the experimental tensile strength values. This equation cannot account for the presence of a breaking line and overestimates the thickness of the loading plane by the depth of the breaking line when in 0 degrees or 22.5 degrees position. If the depth of the breaking line is taken into account, the model predictions and the experimental findings are comparable. Also, in the brittle cracking FEM simulations the predicted crack propagation patterns were similar to those found in the experiments, and the model stress distributions across the lower surfaces were much more homogeneous and streamlined parallel to the loading plane. The brittle cracking model hence reflected the practicalities of the bending test more closely. The findings suggested that with the breaking line facing down fracture should always start in the centre of a tablet at its lower surface, initiated by the breaking line. Due to simultaneous development of larger stresses along the y-axis the tablet should still break into two equal halves along the loading plane, unless the position of the breaking line relative to the loading plane was 22.5 degrees . In this case the tablet would fail by a mixed process, whereby failure would occur mainly along the breaking line, but due to simultaneous crack formation at the lower surface close to the bevel edge parallel to the loading plane the final breaking pattern would deviate from the breaking line about half-way from its centre, as seen in the practical experiments. PMID- 26363110 TI - Delivery of tissue plasminogen activator and streptokinase magnetic nanoparticles to target vascular diseases. AB - Thrombolytic therapy for acute myocardial infarction standardly makes use of the medications streptokinase (SK) and tissue plasminogen activator (tPA). In this study, the potential of silica-coated magnetic nanoparticles (SiO2-MNPs) as nanocarriers clinical thrombolytic therapy was investigated. SiO2-MNPs for use in targeted therapeutic delivery of tPA and SK were prepared using a combined technique incorporating controlled precipitation and hydrothermal methods. Response surface methodology (RSM) was employed to evaluate the efficiency of the SiO2-MNPs. The production of SK secreted from Streptococcus equi was enhanced using random mutagenesis. The tPA and SK A were encapsulated by means of a silanizing agent with a surface rich in 3-aminopropyltrimethoxysilane layered around the SiO2-MNPs. Blood clot lysis assays and fibrin-containing agarose plates were used to carry out in vitro thrombolysis testing. The optimum conditions for producing MNPs were found to be at pH=13 and at a temperature of 75 degrees C for 45 min. Culture conditions of 2.75% NaCl concentration at initial pH=7.5 for 90 s under UV resulted in maximum SK activity. The tPA/SK conjugated SiO2-MNPs (SiO2-MNP-tPA-SK) increased operating stability in whole blood and storage stability in a buffer by 92%. More effective thrombolysis using magnetic targeting was indicated by a 38% reduction in blood clot lysis time achieved with SiO2-MNP-tPA-SK compared to administering the SiO2-MNPs without guidance. The silica-coated magnetic nanocarriers developed in this study show potential for improved clinical thrombolytic therapy. PMID- 26363111 TI - Understanding the impact of media viscosity on dissolution of a highly water soluble drug within a USP 2 mini vessel dissolution apparatus using an optical planar induced fluorescence (PLIF) method. AB - In this study, planar induced fluorescence (PLIF) was used for the first time to evaluate variability in drug dissolution data using Rhodamine-6G doped tablets within small volume USP 2 apparatus. The results were compared with tablets contained theophylline (THE) drug for conventional dissolution analysis. The impact of hydrodynamics, sampling point, dissolution media viscosity and pH were investigated to note effects on release of these two actives from the hydrophilic matrix tablets. As expected mixing performance was poor with complex and reduced velocities at the bottom of the vessel close to the tablet surface; this mixing became even worse as the viscosity of the fluid increased. The sampling point for dissolution can affect the results due to in-homogenous mixing within the vessel; this effect is exacerbated with higher viscosity dissolution fluids. The dissolution profiles of RH-6G measured via PLIF and THE measured using UV analysis were not statistically different demonstrating that RH-6G is an appropriate probe to mimic the release profile of a highly soluble drug. A linear correlation was accomplished between the release data of the drug and the dye (R(2)>0.9). The dissolution profile of the dye, obtained with the analysis of the PLIF images, can be used in order to evaluate how the viscosity and the mixing performance of USP 2 mini vessel affect the interpretation of the dissolution data of the targeted drug. PMID- 26363112 TI - In situ gel-forming AP-57 peptide delivery system for cutaneous wound healing. AB - In situ gel-forming system as local drug delivery system in dermal traumas has generated a great interest. Accumulating evidence shows that antimicrobial peptides play pivotal roles in the process of wound healing. Here in this study, to explore the potential application of antimicrobial peptide in wound healing, biodegradable poly(L-lactic acid)-Pluronic L35-poly(L-lactic acid) (PLLA-L35 PLLA) was developed at first. Then based on this polymer, an injectable in situ gel-forming system composed of human antimicrobial peptides 57 (AP-57) loaded nanoparticles and thermosensitive hydrogel was prepared and applied for cutaneous wound healing. AP-57 peptides were enclosed with biocompatible nanoparticles (AP 57-NPs) with high drug loading and encapsulation efficiency. AP-57-NPs were further encapsulated in a thermosensitive hydrogel (AP-57-NPs-H) to facilitate its application in cutaneous wound repair. As a result, AP-57-NPs-H released AP 57 in an extended period and exhibited quite low cytotoxicity and high anti oxidant activity in vitro. Moreover, AP-57-NPs-H was free-flowing liquid at room temperature, and can form non-flowing gel without any crosslink agent upon applied on the wounds. In vivo wound healing assay using full-thickness dermal defect model of SD rats indicated that AP-57-NPs-H could significantly promote wound healing. At day 14 after operation, AP-57-NPs-H treated group showed nearly complete wound closure of 96.78 +/- 3.12%, whereas NS, NPs-H and AP-57-NPs group recovered by about 68.78 +/- 4.93%, 81.96 +/- 3.26% and 87.80 +/- 4.62%, respectively. Histopathological examination suggested that AP-57-NPs-H could promote cutaneous wound healing through enhancing granulation tissue formation, increasing collagen deposition and promoting angiogenesis in the wound tissue. Therefore, AP-57-NPs-H might have potential application in wound healing. PMID- 26363113 TI - Engineering of Harobin for enhanced fibrinolytic activity obtained by random and site-directed mutagenesis. AB - We have previously published a report on the cloning and characterization of Harobin, a fibrinolytic serine protease. However, the broad application of this fibrinolytic enzyme is limited by its low expression level that was achieved in Pichia pastoris. To counteract this shortcoming, random and site-directed mutagenesis have been combined in order to improve functional expression and activity of Harobin. By screening 400 clones from random mutant libraries for enhanced fibrinolytic activity, two mutants were obtained: N111R, R230G. By performing site-directed mutagenesis, a Harobin double mutant, N111R/R230G, was constructed and can be functionally expressed at higher level than the wild type enzyme. In addition, it possessed much higher fibrinolytic and amidolytic activity than the wild type enzyme and other single mutants. The N111R/R230G expressed in basal salts medium was purified by a three step purification procedure. At pH of 6.0-9.0, and the temperature range of 40-90 degrees C, N111R/R230G was more active and more heat resistant. The fibrinolytic activities of Harobin mutants were completely inhibited by PMSF and SBTI, but not by EDTA, EGTA, DTT, indicating that Harobin is a serine protease. N111R/R230G showed much better anti-thrombosis effect than wild type Harobin and single mutants, and could significantly increase bleeding and clotting time. Intravenous injection of N111R/R230G in spontaneous hypertensive rats (SHR) led to a significant reduction in systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) (p < 0.01), while heart rate (HR) was not affected. The in vitro and in vivo results of the present study revealed that Harobin double mutant N111R/R230G is an appropriate candidate for biotechnological applications due to its high expression level and high activity in area of thrombosis and hypertension. PMID- 26363114 TI - Production of bioactive wheat puroindoline proteins in Nicotiana benthamiana using a virus-based transient expression system. AB - The emergence of antibiotic resistant pathogenic strains of bacteria has necessitated the development of novel antimicrobial agents. The puroindoline A and B (PINA and PINB) proteins of wheat, well-known for their roles in determining the important phenotype of grain texture, are also antimicrobial, making them attractive as natural bio-control agents. However, the biochemical basis of PIN functionality remains unclear due to limitations in expressing them at the required yield and purity and lack of accurate tertiary structure. This study focussed on rapid transient expression of PINs targeted to different subcellular compartments (chloroplast, apoplast, endoplasmic reticulum and cytosol) of Nicotiana benthamiana leaf cells using the deconstructed tobacco mosaic virus-based 'magnICON(r)' system. The expressed recombinant PINs were characterised by Western blot using the Durotest anti-friabilin antibody, enzyme linked immunosorbent assays (ELISA) and antimicrobial activity tests. Maximum yield of the His-tagged PINs occurred when targeted to the chloroplast. Both PINs exhibited oligomeric and monomeric forms on gels, but Western blots with the widely used Durotest anti-friabilin antibody identified only oligomeric forms. Only the PINs purified by a hydrophobic interaction method exhibited monomeric forms with the anti-His tag antibody, indicating correct folding. Interestingly, the Durotest antibody did not bind to monomers, suggesting their epitope may be obscured. PINs purified by His-tag affinity purification under native conditions or by the hydrophobic method exhibited antimicrobial activities. The successful in planta expression and optimisation of purification will enable future studies to examine the detailed structure of the PINs and explore novel bio-control applications in health, food and/or agriculture. PMID- 26363115 TI - Purification of a dimeric arginine deiminase from Enterococcus faecium GR7 and study of its anti-cancerous activity. AB - The arginine deiminase (ADI, E.C 3.5.3.6) - a key enzyme of ADI pathway of Enterococcus faecium GR7 was purified to homogeneity. A sequential purification strategy involving ammonium sulfate fractionation, molecular sieve followed by Sephadex G-100 gel filtration was applied to the crude culture filtrate to obtain a pure enzyme preparation. The enzyme was purified with a fold of 16.92 and showed a final specific activity of 76.65IU/mg with a 49.17% yield. The dimeric ADI has a molecular mass of about 94,364.929Da, and comprises of hetrodimers of 49.1kDa and 46.5kDa as determined by MALDI-TOF and PAGE analysis. To assess anti cancerous activity of ADI by MTT assay was carried out against cancer cell lines (MCF-7, Sp2/0-Ag14 and Hep-G2). Purified ADI exhibited the most profound antiproliferative activity against Hep-G2 cells; with half-maximal inhibitory concentration (IC50) of 1.95MUg/ml. Purified ADI from E. faecium GR7 was observed to induce apoptosis in the Hep-G2 cells by DNA fragmentation assay. Our findings suggest the possibility of a future use of ADI from E. faecium GR7 as a potential anticancer drug. PMID- 26363116 TI - Purification of diverse hemoglobins by metal salt precipitation. AB - Although donated blood is the preferred material for transfusion, its limited availability and stringent storage requirements have motivated the development of blood substitutes. The giant extracellular hemoglobin (aka erythrocruorin) of the earthworm Lumbricus terrestris (LtEc) has shown promise as a blood substitute, but an efficient purification method for LtEc must be developed to meet the potential large demand for blood substitutes. In this work, an optimized purification process that uses divalent and trivalent metal salts to selectively precipitate human, earthworm, and bloodworm hemoglobin (HbA, LtEc, and GdHb, respectively) from crude solutions was developed. Although several metal ions were able to selectively precipitate LtEc, Zn(2+) and Ni(2+) provided the lowest heme oxidation and highest overall yield of LtEc. In contrast, Zn(2+) was the only metal ion that completely precipitated HbA and GdHb. Polyacrylamide gel electrophoresis (PAGE) analysis shows that metal precipitation removes several impurities to provide highly pure hemoglobin samples. Heme oxidation levels were relatively low for Zn(2+)-purified HbA and LtEc (2.4+/-1.3% and 5.3+/-2.1%, respectively), but slightly higher for Ni(2+)-purified LtEc (8.4+/-1.2%). The oxygen affinity and cooperativity of the precipitated samples are also identical to samples purified with tangential flow filtration (TFF) alone, indicating the metal precipitation does not significantly affect the function of the hemoglobins. Overall, these results show that hemoglobins from several different species can be highly purified using a combination of metal (Zn(2+)) precipitation and tangential flow filtration. PMID- 26363117 TI - Overexpression, purification and enzymatic characterization of a recombinant Arabian camel Camelus dromedarius glucose-6-phosphate dehydrogenase. AB - In a previous study the full-length open reading frame of the Arabian camel, Camelus dromedarius liver cytosolic glucose-6-phosphate dehydrogenase (G6PD) cDNA was determined using reverse transcription polymerase chain reaction. The C. dromedarius cDNA was found to be 1545 nucleotides (accession number JN098421) that encodes a protein of 515 amino acids residues. In the present study, C. dromedarius recombinant G6PD was heterologously overexpressed in Escherichia coli BL21 (DE3) pLysS and purified by immobilized metal affinity fast protein liquid chromatography (FPLC) in a single step. The purity and molecular weight of the enzyme were analyzed on SDS-PAGE and the purified enzyme showed a single band on the gel with a molecular weight of 63.0 KDa. The specific activity was determined to be 2000 EU/mg protein. The optimum temperature and pH were found to be 60 degrees C and 7.4, respectively. The isoelectric point (pI) for the purified G6PD was determined to be 6.4. The apparent Km values for the two substrates NADP+ and G6P were found to be 23.2 MUM and 66.7 MUM, respectively. The far-UV circular dichroism (CD) spectra of G6PD showed that it has two minima at 208 and 222 nm as well as maxima at 193 nm which is characteristic of high content of alpha-helix. Moreover, the far-UV CD spectra of the G6PD in the presence or absence of NADP+ were nearly identical. PMID- 26363118 TI - Characterization of recombinant homocitrate synthase from Candida albicans. AB - LYS21 and LYS22 genes from Candida albicans encoding isoforms of homocitrate synthase (HCS), an enzyme catalyzing the first committed step in the l-lysine biosynthetic pathway, were cloned and expressed as N-oligoHistagged fusion proteins in Escherichia coli. The purified gene products revealed HCS activity, i.e. catalyzed the condensation of alpha-ketoglutarate with acetyl-coenzyme A to yield homocitrate. The recombinant enzymes were purified to homogeneity and characterized for their physical properties and substrate specificities. As determined by size-exclusion chromatography (SEC) and native page electrophoresis, both isoenzymes adopt multiple quaternary structures, with the homotetrameric one being the most abundant. The KM (acetyl-CoA)=0.8+/-0.15mM and KM (alpha-ketoglutarate)=0.113+/-0.02mM for His6CaLys21p and KM (acetyl CoA)=0.48+/-0.09mM and KM (alpha-ketoglutarate)=0.152+/-0.03mM values for His6CaLys22p were determined. Both enzyme versions were inhibited by l-Lys, i.e. the end product of the alpha-aminoadipate pathway but Lys22p was more sensitive than Lys21p, with Ki (L-Lys)=128+/-8MUM for His6CaLys21p and Ki (L-Lys)=4.37+/ 0.68MUM for His6CaLys22p. The isoforms of C. albicans HCS exhibited differential sensitivity to several l-Lys analogues. Most notably, dl-alpha difluoromethyllysine strongly inhibited His6CaLys22p (IC50 32+/-3MUM) but was not inhibitory at all towards His6CaLys21p. Differential sensitivity of recombinant C. albicans Deltalys21/LYS22, LYS21/Deltalys22 and Deltalys21/Deltalys22 mutant strains to lysine analog, 2-aminoethyl-l-cysteine and biochemical properties of homocitrate synthase isoforms suggest different roles of two HCS isoenzymes in alpha-aminoadipate pathway. PMID- 26363119 TI - Cloning and expression of phosphoenolpyruvate carboxykinase from a cestode parasite and its solubilization from inclusion bodies using l-arginine. AB - Phosphoenolpyruvate carboxykinase is an essential regulatory enzyme of glycolysis in the cestode parasite, Raillietina echinobothrida, and is considered a potential target for anthelmintic action because of its differential activity from that of its avian host. However, due to the unavailability of its structure, the mechanism of regulation of PEPCK from R. echinobothrida (rePEPCK) and its interaction with possible modulators remain unclear. Hence, in this study, the rePEPCK gene was cloned into pGEX-4T-3 and overexpressed for its characterization. On being induced by IPTG, the recombinant rePEPCK was expressed as inclusion bodies (IBs); hence, various agents, like different inducer concentrations, temperature, time, host cell types, culture media, pH, and additives, were used to bring the protein to soluble form. Finally, a significant amount (~46%) of rePEPCK was solubilized from IBs by adding 2M l-arginine. Near UV circular dichroism spectra analysis indicated that l-arginine (2M) had no effect on the conformation of the protein. In this study, we have reported a yield of ~73mg of purified rePEPCK per 1L of culture. The purified rePEPCK retained its biological activity, and Km of the enzyme for its substrate was determined and discussed. The availability of recombinant rePEPCK may help in biochemical- and biophysical-studies to explore its molecular mechanisms and regulations. PMID- 26363120 TI - Purification, characterization, and crystallization of membrane bound Escherichia coli tyrosine kinase. AB - Escherichia coli tyrosine kinase (Etk) is a membrane bound kinase in gram negative bacteria that regulates the export of capsular polysaccharides (CPS). The molecular mechanism behind CPS regulation remains unclear, despite access to a crystal structure of the cytoplasmic kinase domain of Etk. In this study, an efficient protocol to produce full length Etk solubilized in n-dodecyl-beta-d maltoside has been established with high yield. We have determined that detergent solubilized Etk retains kinase activity, but the protein is prone to aggregation, degradation, and has been unsuccessful in protein crystallization trials. In response, we designed and characterized truncations of Etk that do not aggregate and have led to successful crystallization experiments. In this article, we discuss our optimized expression and purification protocol for Etk, the design of Etk protein truncations, and the behavior of Etk during purification in a range of stabilizing detergents. These efforts have successfully produced protein suitable for crystallization. Our results will be a useful guide for future structural and functional studies of the bacterial tyrosine kinase family. PMID- 26363121 TI - Expression and purification of HER2 extracellular domain proteins in Schneider2 insect cells. AB - Overexpression of human epidermal growth factor receptor 2 (HER2/ErbB2/Neu) results in ligand independent activation of kinase signaling and is found in about 30% of human breast cancers, and is correlated with a more aggressive tumor phenotype. The HER2 extracellular domain (ECD) consists of four domains - I, II, III and IV. Although the role of each domain in the dimerization and activation of the receptor has been extensively studied, the role of domain IV (DIV) is not clearly understood yet. In our previous studies, we reported peptidomimetic molecules inhibit HER2:HER3 heterodimerization. In order to study the binding interactions of peptidomimetics with HER2 DIV in detail, properly folded recombinant HER2 protein in pure form is important. We have expressed and purified HER2 ECD and DIV proteins in the Drosophila melanogaster Schneider2 (S2) cell line. Using the commercial Drosophila expression system (DES), we transfected S2 cells with plasmids designed to direct the expression of secreted recombinant HER2 ECD and DIV proteins. The secreted proteins were purified from the conditioned medium by filtration, ultrafiltration, dialysis and nickel affinity chromatography techniques. The purified HER2 proteins were then analyzed using Western blot, mass spectrometry and circular dichroism (CD) spectroscopy. PMID- 26363122 TI - BacMam production of active recombinant lecithin-cholesterol acyltransferase: Expression, purification and characterization. AB - Lecithin-cholesterol acyltransferase (LCAT) is a key enzyme in the esterification of cholesterol and its subsequent incorporation into the core of high density lipoprotein (HDL) particles. It is also involved in reverse cholesterol transport (RCT), the mechanism by which cholesterol is removed from peripheral cells and transported to the liver for excretion. These processes are involved in the development of atherosclerosis and coronary heart disease (CHD) and may have therapeutic implications. This work describes the use of baculovirus as a transducing vector to express LCAT in mammalian cells, expression of the recombinant protein as a high-mannose glycoform suitable for deglycosylation by Endo H and its purification to homogeneity and characterization. The importance of producing underglycosylated forms of secreted glycoproteins to obtain high resolution crystal structures is discussed. PMID- 26363123 TI - Reverse transcription loop-mediated isothermal amplification for rapid and quantitative assay of covert mortality nodavirus in shrimp. AB - A disease known as covert mortality disease has become an increasing problem in the shrimp farming industry in recent years in China and several countries of Southeast Asia, leading to serious losses in production. Litopenaeus vannamei (also known as Pacific white shrimp) is affected by this disease that leads to a range of clinical symptoms including hepatopancreas atrophy and necrosis, soft shell, slow growth, and abdominal muscle whitening and necrosis in the acute stage of disease. A new nodavirus, termed covert mortality nodavirus (CMNV), has been shown to be the etiological agent. In this study, we report a sensitive and specific real-time reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay for the rapid and quantitative detection of CMNV. The optimal conditions for this newly developed RT-LAMP reaction were found to be 6mM MgCl2 and 1.6mM dNTPs, an incubation temperature of 65 degrees C and a reaction time of 50min. The analytical sensitivity of the RT-LAMP assay was estimated to be 6.3pg total RNA of CMNV-infected shrimp and 27 copies of the target plasmid. The diagnostic sensitivity and specificity of the newly developed assay versus the standard nested reverse transcription PCR (RT-PCR) assay was 96.4% and 94.4%, respectively. The reaction products were detected by visual inspection after staining with an in-tube DNA fluorescent dye, a measure taken to eliminate the risk of contamination. The quantitative RT-LAMP assay for CMNV showed high correlation coefficient (r2=0.9953) when the initial templates were above 1000 copies, however the correlation coefficient decreased when the initial templates were lower than 1000 copies. Test of viral load in shrimp indicated that the viral loads varied from 1.5*102 to 6.7*106 copies per mg of cephalothorax tissue. Thus, the CMNV RT-LAMP assay is a sensitive and specific new tool for the field detection and quantification of CMNV in the diagnosis and surveillance of covert mortality disease. PMID- 26363125 TI - The evolution of animal genomes. AB - Genome sequences are now available for hundreds of species sampled across the animal phylogeny, bringing key features of animal genome evolution into sharper focus. The field of animal evolutionary genomics has focused on identifying and classifying the diversity genomic features, reconstructing the history of evolutionary changes in animal genomes, and testing hypotheses about the evolutionary relationships of animals. The grand challenges moving forward are to connect evolutionary changes in genomes with particular evolutionary changes in phenotypes, and to determine which changes are driven by selection. This will require far greater genome sampling both across and within species, extensive phenotype data, a well resolved animal phylogeny, and advances in comparative methods. PMID- 26363124 TI - Bacterial CRISPR: accomplishments and prospects. AB - In this review we briefly describe the development of CRISPR tools for genome editing and control of transcription in bacteria. We focus on the Type II CRISPR/Cas9 system, provide specific examples for use of the system, and highlight the advantages and disadvantages of CRISPR versus other techniques. We suggest potential strategies for combining CRISPR tools with high-throughput approaches to elucidate gene function in bacteria. PMID- 26363127 TI - Perspectives of Clinicians Involved in the RESTART-Study: Outcomes of a Focus Group. AB - PURPOSE: The purpose of this study was to explore the attitudes and beliefs of speech-language pathologists (SLPs) with regard to the Lidcombe Program and Demands and Capacities-based treatment and to examine how these attitudes and beliefs might have changed as a result of participating in the RESTART-study. METHOD: A focus group meeting with 13 SLPs was organized. The discussion was structured using questions on therapy preference, attitudes about and explicit comparison of both treatments and treatment manuals, and learnings of trial participation. RESULTS: Four main themes were identified. First, a change in attitude toward treatment choice was observed. Second, this change was related to a change in beliefs about the potential of both treatments. Third, aspects of the treatments regarded as success factors were considered. Last, learning outcomes and increased professionalism as a result of participating in the RESTART-trial were discussed. CONCLUSIONS: This study showed how attitudes and beliefs of SLPs with regard to the Lidcombe Program and Demands and Capacities-based treatment evolved during a randomized trial. This work increases our understanding of the role of attitudes and beliefs in the uptake and utilization of therapies and demonstrates the importance of collecting qualitative data. Results and recommendations should prove of value in implementing the RESTART-trial results and in training SLPs. PMID- 26363126 TI - Perturbed meibomian gland and tarsal plate morphogenesis by excess TGFalpha in eyelid stroma. AB - Transforming growth factor alpha (TGFalpha) belongs to the epidermal growth factor (EGF) family and is known to play an important role during eyelid morphogenesis. In this study, we showed that ectopic expression of TGFalpha in the stroma of Kera-rtTA/tet-O-TGFalpha bitransgenic mice results in precocious eye opening, abnormal morphogenesis of the meibomian gland, tendon and tarsal plate malformation and epithelium hyperplasia. TGFalpha did not change proliferation and differentiation of meibocytes, but promoted proliferation and inhibited differentiation of the tarsal plate tenocytes. These results suggest that proper formation of the tendon and tarsal plate in the mouse eyelid is required for normal morphogenesis of the meibomian gland. PMID- 26363129 TI - Cognitive intermediate phenotype and genetic risk for psychosis. AB - Intermediate phenotypes (IPs) are defined as measurable liability traits underlying complex phenotypes, posited to be more genetically tractable than the phenotypes themselves. Here we review evidence for cognition as an IP of psychosis, and highlight topical advances in the literature: first, heritability estimation of cognitive abilities using genomewide complex-trait analysis; second, evidence that cognition lies upstream to schizophrenia liability; third, use of polygenic risk scores rather than single genetic variants to examine genetic overlap between cognitive IPs and schizophrenia; and fourth, use of cognitive IPs for schizophrenia risk gene discovery and functional characterization. We end with future directions in using cognitive IPs to study genetic risk of psychosis, including methodological refinements and shifting research focus from identifying IPs to using them. PMID- 26363128 TI - The MANDELA study: A multicenter, randomized, open-label, parallel group trial to refine the use of everolimus after heart transplantation. AB - In recent years a series of trials has sought to define the optimal protocol for everolimus-based immunosuppression in heart transplantation, with the goal of minimizing exposure to calcineurin inhibitors (CNIs) and harnessing the non immunosuppressive benefits of everolimus. Randomized studies have demonstrated that immunosuppressive potency can be maintained in heart transplant patients receiving everolimus despite marked CNI reduction, although very early CNI withdrawal may be inadvisable. A potential renal advantage has been shown for everolimus, but the optimal time for conversion and the adequate reduction in CNI exposure remain to be defined. Other reasons for use of everolimus include a substantial reduction in the risk of cytomegalovirus infection, and evidence for inhibition of cardiac allograft vasculopathy, a major cause of graft loss. The ongoing MANDELA study is a 12-month multicenter, randomized, open-label, parallel group study in which efficacy, renal function and safety are compared in approximately 200 heart transplant patients. Patients receive CNI therapy, steroids and everolimus or mycophenolic acid during months 3 to 6 post transplant, and are then randomized at month 6 post-transplant (i) to convert to CNI-free immunosuppression with everolimus and mycophenolic acid or (ii) to continue reduced-exposure CNI, with concomitant everolimus. Patients are then followed to month 18 post-transplant The rationale and expectations for the trial and its methodology are described herein. PMID- 26363130 TI - Elevational speciation in action? Restricted gene flow associated with adaptive divergence across an altitudinal gradient. AB - Evolutionary theory predicts that divergent selection pressures across elevational gradients could cause adaptive divergence and reproductive isolation in the process of ecological speciation. Although there is substantial evidence for adaptive divergence across elevation, there is less evidence that this restricts gene flow. Previous work in the boreal chorus frog (Pseudacris maculata) has demonstrated adaptive divergence in morphological, life history and physiological traits across an elevational gradient from approximately 1500-3000 m in the Colorado Front Range, USA. We tested whether this adaptive divergence is associated with restricted gene flow across elevation - as would be expected if incipient speciation were occurring - and, if so, whether behavioural isolation contributes to reproductive isolation. Our analysis of 12 microsatellite loci in 797 frogs from 53 populations revealed restricted gene flow across elevation, even after controlling for geographic distance and topography. Calls also varied significantly across elevation in dominant frequency, pulse number and pulse duration, which was partly, but not entirely, due to variation in body size and temperature across elevation. However, call variation did not result in strong behavioural isolation: in phonotaxis experiments, low-elevation females tended to prefer an average low-elevation call over a high-elevation call, and vice versa for high-elevation females, but this trend was not statistically significant. In summary, our results show that adaptive divergence across elevation restricts gene flow in P. maculata, but the mechanisms for this potential incipient speciation remain open. PMID- 26363131 TI - Determination of LC50 and sub-chronic neurotoxicity of diesel exhaust nanoparticles. AB - Air pollution is a major problem faced globally and is seen associated with central nervous system (CNS) disorders like neuropathology and neuro inflammation. Here, we investigated the CNS disorders as a result of sub-chronic exposure (90 days) to diesel exhaust nanoparticles (DENPs) and explored the minimal levels of DENPs needed to exhibit the early mediators of neuro inflammation and neuropathology. Male and female wistar rats (6 rats per group) were exposed to DENPs (1/5th, 1/10th and 1/15th LC50) by inhalation for 4h per day, 5 days per week over 90 days and neurotoxicity end-points were analyzed. DENP exposure caused elevation in levels of pro-inflammatory cytokines, amyloid beta 42 (Abeta 42), reactive oxygen species (ROS), hydrogen peroxide (H2O2), nitrate (NO3(-)), nitrite (NO2(-)) and apurinic/apyrimidinic sites (AP) at varying degrees at different sections of rat brain. Hence, exposure to DENPs resulted in dose-dependent toxicity and was closely correlated to increased inflammation, DNA damage and oxidative stress. PMID- 26363132 TI - Cytotoxic effect of nanosilver particles on testicular tissue: Evidence for biochemical stress and Hsp70-2 protein expression. AB - Lastly, there are growing evidences that nanosilver (NS) particles highly induce cytotoxic impacts in vitro and in vivo. Here, we analyzed the dose dependent effect of NS on histological changes, biochemical alterations and endocrine statuses, sperm parameters as well as chaperone Hsp70-2 expression. NS particles (50-60nm) were administrated in 3 doses of 0.5, 1 and 5mg/kg, intraperitoneally, for 35 days. The 0.3mL normal saline was administrated in control-sham group. Histological alterations, sperm parameters, serum levels of LH, FSH and testosterone were evaluated. Germinal and Leydig cells RNA damage, Leydig cells steroidogenic foci, the testicular and sperm total antioxidant capacity (TAC), malondialdehyde (MDA), nitric oxide (NO) levels, immunohistochemical (IHC) expression and mRNA level of Hsp70-2 were analyzed. The NS, dose dependently, resulted in enhanced germinal cells degeneration, necrosis, seminiferous tubules atrophy and decreased serum levels of LH, FSH and testosterone. Elevated germinal and Leydig cells RNA damage associated with increased sperm abnormalities were observed in NS-treated groups. Expression of Hsp70-2 was up-regulated in 0.5mg/kg, while its expression was decreased in 1 and 5mg/kg NS-treated groups. Testicular and sperm TAC levels reduced. However, the MDA and NO levels significantly (P<0.05) increased in all NS-treated groups. No histological and biochemical changes were detected in control-sham group. In conclusion, the NS particles exert their pathological impact via affecting testicular antioxidant and endocrine statuses, which in turn lead to diminished expression of Hsp70-2. Ultimately, by this mechanism NS particles adversely impact the cellular RNA, DNA and protein contents. PMID- 26363133 TI - Effects of subcytotoxic cadmium on morphology of glial fibrillary acidic protein network in astrocytes derived from murine neural stem/progenitor cells. AB - The susceptibility of mouse neural stem/progenitor cells (NSPCs) to heavy-metal cytotoxicity was assessed by measuring cell viability following exposure to heavy metal chlorides (ZnCl2, CdCl2, CuCl2, and HgCl2, respectively). We determined half-maximal inhibitory concentration (IC50) values, subcytotoxic doses, capacity for neural differentiation, and morphological features of glial fibrillary acidic protein (GFAP) network at the subcytotoxic doses of heavy metal ions. Experiments were performed using two protocols for the exposure at subcytotoxic doses of heavy metal ions; these protocols included simultaneous exposure with the induction of NSPC differentiation and sequential exposure after the induction for 1 week. Exposure to HgCl2 using both protocols reduced the ratio of neuronal NSPC differentiation. Although sequential exposure to CdCl2 reduced the size of GFAP network, simultaneous exposure did not induce any change. In conclusion, image analyses of the cytoskeletal morphology of NSPCs as a novel tool for assessing neurodevelopmental cytotoxicity enabled us to obtain new information about the localization of cytoskeletal proteins. PMID- 26363134 TI - Bioaccumulation of decamethylpentacyclosiloxane (D5): A review. AB - Decamethylpentacyclosiloxane (D5) is a widely used, high-production volume personal care product with an octanol-water partition coefficient (log K(OW)) of 8.09. Because of D5's high K(OW) and widespread use, it is subject to bioaccumulation assessments in many countries. The present study provides a compilation and an in-depth, independent review of bioaccumulation studies involving D5. The findings indicate that D5 exhibits depuration rates in fish and mammals that exceed those of extremely hydrophobic, nonbiotransformable substances; that D5 is subject to biotransformation in mammals and fish; that observed bioconcentration factors in fish range between 1040 L/kg and 4920 L/kg wet weight in laboratory studies using non-radiolabeled D5 and between 5900 L/kg and 13 700 L/kg wet weight in an experiment using C(14) radiolabeled D5; and that D5 was not observed to biomagnify in most laboratory experiments and field studies. Review of the available studies shows a high degree of internal consistency among findings from different studies and supports a broad comprehensive approach in bioaccumulation assessments that includes information from studies with a variety of designs and incorporates multiple bioaccumulation measures in addition to the K(OW) and bioconcentration factor. PMID- 26363135 TI - HhAntag, a Hedgehog Signaling Antagonist, Suppresses Chondrogenesis and Modulates Canonical and Non-Canonical BMP Signaling. AB - Chondrogenesis subtends the development of most skeletal elements and involves mesenchymal cell condensations differentiating into growth plate chondrocytes that proliferate, undergo hypertrophy, and are replaced by bone. In the pediatric disorder Hereditary Multiple Exostoses, however, chondrogenesis occurs also at ectopic sites and causes formation of benign cartilaginous tumors--exostoses- near the growth plates. No treatment is currently available to prevent or reverse exostosis formation. Here, we asked whether chondrogenesis could be stopped by targeting the hedgehog pathway, one of its major regulators. Micromass cultures of limb mesenchymal cells were treated with increasing amounts of the hedgehog inhibitor HhAntag or vehicle. The drug effectively blocked chondrogenesis and did so in a dose-dependent manner as monitored by: alcian blue-positive cartilage nodule formation; gene expression of cartilage marker genes; and reporter activity in Gli1-LacZ cell cultures. HhAntag blocked chondrogenesis even when the cultures were co-treated with bone morphogenetic protein 2 (rhBMP-2), a strong pro-chondrogenic factor. Immunoblots showed that HhAntag action included modulation of canonical (pSmad1/5/8) and non-canonical (pp38) BMP signaling. In cultures co-treated with HhAntag plus rhBMP-2, there was a surprising strong up regulation of pp38 levels. Implantation of rhBMP-2-coated beads near metacarpal elements in cultured forelimb explants induced formation of ectopic cartilage that however, was counteracted by HhAntag co-treatment. Collectively, our data indicate that HhAntag inhibits not only hedgehog signaling, but also modulates canonical and non-canonical BMP signaling and blocks basal and rhBMP2-stimulated chondrogenesis, thus representing a potentially powerful drug-based strategy to counter ectopic cartilage growth or induce its involution. PMID- 26363136 TI - Alexidine Dihydrochloride Attenuates Osteoclast Formation and Bone Resorption and Protects Against LPS-Induced Osteolysis. AB - Aseptic loosening and periprosthetic infection leading to inflammatory osteolysis is a major complication associated with total joint arthroplasty (TJA). The liberation of bacterial products and/or implant-derived wear particles activates immune cells that produce pro-osteoclastogenic cytokines that enhance osteoclast recruitment and activity, leading to bone destruction and osteolysis. Therefore, agents that prevent the inflammatory response and/or attenuate excessive osteoclast (OC) formation and bone resorption offer therapeutic potential by prolonging the life of TJA implants. Alexidine dihydrochloride (AD) is a bisbiguanide compound commonly used as an oral disinfectant and in contact lens solutions. It possesses antimicrobial, anti-inflammatory and anticancer properties; however, its effects on OC biology are poorly described. Here, we demonstrate that AD inhibits OC formation and bone resorption in vitro and exert prophylatic protection against LPS-induced osteolysis in vivo. Biochemical analysis demonstrated that AD suppressed receptor activator of NF-kappaB ligand (RANKL)-induced activation of mitogen-activated protein kinases (ERK, p38, and JNK), leading to the downregulation of NFATc1. Furthermore, AD disrupted F-actin ring formation and attenuated the ability of mature OC to resorb bone. Collectively, our findings suggest that AD may be a promising prophylactic anti osteoclastic/resorptive agent for the treatment of osteolytic diseases caused by excessive OC formation and function. PMID- 26363137 TI - Ventral striatal gamma oscillations are highly variable from trial to trial, and are dominated by behavioural state, and only weakly influenced by outcome value. AB - The human and rodent ventral striatal local field potentials show striking oscillations in the gamma band (~ 40-100 Hz), which have been linked to aspects of behaviour such as reward anticipation and delivery, movement initiation, learning from feedback, and decision-making. These oscillations show a rich temporal organization, whose relationship with behavioural variables is not well understood. Here, we show that, in rats performing a conditioned approach task, low-gamma and high-gamma oscillations during an immobile reward anticipation epoch were largely insensitive to outcome value, even though rats distinguished behaviourally between different outcomes, and single units encoded outcome value. Behaviour was highly stereotyped, yet we observed large variability from trial to trial in the occurrence and timing of these oscillations. Furthermore, higher order features such as high-gamma power leading low-gamma power, and phase amplitude coupling to lower-frequency bands, were only marginally modulated by outcome value. Moreover, these patterns closely resembled those found during off task rest periods in which no rewards could be earned. These observations suggest a new interpretation of ventral striatal gamma oscillations as reflecting a default or resting state, with only minor and highly variable modulation by specific task-related variables. PMID- 26363138 TI - Factors Influencing Choices of Contextualized Versus Traditional Practices With Children and Adolescents Who Have Traumatic Brain Injury. AB - PURPOSE: This preliminary investigation examined speech-language pathologists' (SLPs') use of contextualized practices (i.e., functional, personally relevant, nonhierarchical, and collaborative) compared with traditional practices (i.e., clinical, generic, hierarchical, and expert driven) with school-age children and adolescents with traumatic brain injury (TBI). METHODS: An electronic survey asked SLPs about their use of clinical activities described as more or less contextualized. Research questions focused on frequency of using contextualized practices and factors associated with their use or nonuse. RESULTS: Seventy responses met criteria for analysis; 98% of these participants reported using at least 1 contextualized practice. Higher use of contextualized practices was associated with working in schools compared to health care settings, access to experts, and greater experience with TBI. Most frequently cited reasons for not using contextualized practices included not fitting the student and scheduling issues. CONCLUSIONS: Factors associated with using contextualized practices suggest that access to experts and experience with TBI are critical components for facilitating contextualized practice recommendations. Reasons for not using certain contextualized practices highlight the need to address scheduling issues and to increase education about practices that may best meet the unique needs of students with TBI. PMID- 26363139 TI - Whole transcriptome profiling of adult and infective stages of the trematode Opisthorchis felineus. AB - Opisthorchis felineus, the trematode belonging to the family Opisthorchiidae, is a causative agent of the infection called opisthorchiasis or liver fluke infection. Being a close relative of Opisthorchis viverrini and Clonorchis sinensis (oriental liver flukes) it is encountered in northern Eurasia, especially in Russia, Kazakhstan, Belarus, Ukraine, and Baltic countries. Whole genome data for oriental liver flukes revealed their adaptations for life in the bile duct but our knowledge of O. felineus is scarce. To address this knowledge gap and uncover evolutionary aspect of the adaptations on the transcriptomic level, we used RNA-sequencing approach to investigate two stages of the parasite residing in different hosts. Bioinformatic analysis revealed specific features affecting various biochemical pathways and gene networks. Namely, we observed the loss of genes involved in polyamine synthesis, methionine salvage and peroxisome biogenesis. Some of the gene families, like MD-2 lipid binding proteins, calmodulins and cathepsins on the contrary have expanded compared to free living eukaryotes. We identified significant differences between the stages in homeodomain-containing genes, G-protein coupled receptors, and neuroactive signaling systems. Granulin-like growth factors specific for O. felineus were also identified. In this work, we provide the first whole transcriptome investigation of this parasite. We also hope that these results will create a background for further molecular research of helminth infections and opisthorchiasis in particular. PMID- 26363140 TI - The executive control network and symptomatic improvement in attention deficit/hyperactivity disorder. AB - BACKGROUND: One neurodevelopmental theory hypothesizes remission of attention deficit/hyperactivity disorder (ADHD) to result from improved prefrontal top-down control, while ADHD, independent of the current diagnosis, is characterized by stable non-cortical deficits (Halperin & Schulz, 2006). We tested this theory using resting state functional MRI (fMRI) data in a large sample of adolescents with remitting ADHD, persistent ADHD, and healthy controls. METHODS: Participants in this follow-up study were 100 healthy controls and 129 adolescents with ADHD combined type at baseline (mean age at baseline 11.8 years; at follow-up 17.5 years). Diagnostic information was collected twice and augmented with magnetic resonance imaging (MRI) scanning at follow-up. We used resting state functional connectivity (RSFC) of the executive control network to investigate whether improved prefrontal top-down control was related to a developmental decrease in ADHD symptoms. In addition, we tested whether non-cortical RSFC, i.e., cerebellar and striatal RSFC, was aberrant in persistent and/or remittent ADHD compared to controls. RESULTS: Higher connectivity within frontal regions (anterior cingulate cortex) of the executive control network was related to decreases in ADHD symptoms. This association was driven by change in hyperactive/impulsive symptoms and not by change in inattention. Participants with remitting ADHD showed stronger RSFC than controls within this network, while persistent ADHD cases exhibited RSFC strengths intermediate to remittent ADHD cases and controls. Cerebellar and subcortical RSFC did not differ between participants with ADHD and controls. CONCLUSIONS: In line with the neurodevelopmental theory, symptom recovery in ADHD was related to stronger integration of prefrontal regions in the executive control network. The pattern of RSFC strength across remittent ADHD, persistent ADHD, and healthy controls potentially reflects the presence of compensatory neural mechanisms that aid symptomatic remission. PMID- 26363141 TI - Salivirus type 1 and type 2 in patients with acute gastroenteritis, Germany. AB - BACKGROUND: Salivirus (SaV-A) is a novel member of the family Picornaviridae and has been associated with acute gastroenteritis. Recently, a second type of SaV-A, SaV-A2, was identified in a sewage sample from Bangkok, Thailand. No information is available on the prevalence of SaV-A in Western Europe. OBJECTIVES: Stool samples from patients with symptoms of acute viral gastroenteritis were analyzed for SaV-A and the clinical course of SaV-A-positive individuals was evaluated. STUDY DESIGN: A total of 3019 fecal samples collected during 2012-2013 from 1941 hospitalized patients with acute gastroenteritis were screened for SaV-A by a newly designed real-time reverse transcription polymerase chain reaction targeting a conserved sequence in the 5'-untranslated region. Positive results were verified by sequencing the viral capsid protein 1 gene also allowing typing of the virus. Medical records of SaV-A-infected patients were reviewed for clinical features and laboratory data. RESULTS: SaV-A was detected in five patients. Viral RNA concentrations ranged from 7.1*10(6) to 7.2*10(8)copies/g feces. The viruses from four patients were classified as SaV-A1 while SaV-A2 was present in one patient. After reviewing the medical records, SaV-A could not be considered as the sole possible cause of gastroenteritis symptoms given the presence of other plausible causes in all five patients. CONCLUSION: SaV-A infection can be detected in Germany, Western Europe, albeit at low levels. The detection of SaV-A2 in Europe suggests wider spread of SaV-A2. Presence of SaV-A, even at high concentrations, in a stool sample provides no conclusive evidence that SaV is the major cause of the patient's gastroenteritis symptoms. PMID- 26363142 TI - Monitoring the patient response as an alternative to commercial negative quality control in infectious serology. AB - BACKGROUND: Traditional internal quality control schemes for qualitative infectious serology mostly rely on the use of commercial positive and negative quality control materials. However, with respect to the negative control, target values provided by the manufacturer are often poorly defined and non commutability of the commercial materials further complicates correct interpretation of control results. An alternative quality control procedure using the median patient seronegative response is presented. STUDY DESIGN: Daily patient median responses were calculated for our Hepatitis B surface antigen, Hepatitis B core antibody, Hepatitis C antibody and HIV antigen/antibody test systems. Because of the low prevalence of these viruses in our area, most patient responses are negative. A minimum of 5 patient samples per day was required to generate a stable daily median. Control limits were calculated and daily patient medians were plotted against commercial quality control results. RESULTS: Commercial negative controls and daily patient medians mostly behaved in the same way. Nevertheless, for the Hepatitis B surface antigen test, patient medians frequently exceeded the calculated control limit in contrast to commercial quality controls. This confirms that target ranges provided by the manufacturer are not always adequate. Moreover, an important matrix-related interference occurred on our HIV antigen/antibody test system and correct interpretation was only possible using daily patient median results. CONCLUSION: Monitoring the daily patient median response can be a valuable alternative to traditional commercial negative quality control. It's easy to perform, cost-free, provides additional information with respect to matrix effects and allows for the establishment of well-defined control limits. PMID- 26363144 TI - Tracing enteric pathogen contamination in sub-Saharan African groundwater. AB - Quantitative PCR (qPCR) can rapidly screen for an array of faecally-derived bacteria, which can be employed as tracers to understand groundwater vulnerability to faecal contamination. A microbial DNA qPCR array was used to examine 45 bacterial targets, potentially relating to enteric pathogens, in 22 groundwater supplies beneath the city of Kabwe, Zambia in both the dry and subsequent wet season. Thermotolerant (faecal) coliforms, sanitary risks, and tryptophan-like fluorescence, an emerging real-time reagentless faecal indicator, were also concurrently investigated. There was evidence for the presence of enteric bacterial contamination, through the detection of species and group specific 16S rRNA gene fragments, in 72% of supplies where sufficient DNA was available for qPCR analysis. DNA from the opportunistic pathogen Citrobacter freundii was most prevalent (69% analysed samples), with Vibrio cholerae also perennially persistent in groundwater (41% analysed samples). DNA from other species such as Bifidobacterium longum and Arcobacter butzleri was more seasonally transient. Bacterial DNA markers were most common in shallow hand-dug wells in laterite/saprolite implicating rapid subsurface pathways and vulnerability to pollution at the surface. Boreholes into the underlying dolomites were also contaminated beneath the city highlighting that a laterite/saprolite overburden, as occurs across much of sub-Saharan aquifer, does not adequately protect underlying bedrock groundwater resources. Nevertheless, peri-urban boreholes all tested negative establishing there is limited subsurface lateral transport of enteric bacteria outside the city limits. Thermotolerant coliforms were present in 97% of sites contaminated with enteric bacterial DNA markers. Furthermore, tryptophan-like fluorescence was also demonstrated as an effective indicator and was in excess of 1.4MUg/L in all contaminated sites. PMID- 26363145 TI - Influence of catchment vegetation on mercury accumulation in lake sediments from a long-term perspective. AB - Organic matter (OM) cycling has a large impact on the cycling of mercury (Hg) in the environment. Hence, it is important to have a thorough understanding on how changes in, e.g., catchment vegetation - through its effect on OM cycling - affect the behavior of Hg. To test whether shifts in vegetation had an effect on Hg-transport to lakes we investigated a sediment record from Herrenwieser See (Southern Germany). This lake has a well-defined Holocene vegetation history: at ~8700years BP Corylus avellana (hazel) was replaced by Quercus robur (oak), which was replaced by Abies alba (fir) and Fagus sylvatica (beech) ~5700years BP). We were particularly interested in testing if coniferous vegetation leads to a larger export of Hg to aquatic systems than deciduous vegetation. When hazel was replaced by oak, reduced soil erosion and increased transport of DOM-bound mercury from the catchment resulted in increases in both Hg-concentrations and accumulation rates (61ngg(-1) and 5.5ngcm(-2)yr.(-)(1) to 118ngg(-1) and 8.5ngcm( 2)yr.(-)(1)). However, even if Hg-concentrations increased also in association with the introduction of fir and beech (173ngg(-1)), as a result of higher Hg:C, there was no increase in Hg-accumulation rates (7.6ngcm(-2)yr.(-)(1)), because of a decreased input of OM. At around 2500years BP Hg-accumulation rates and Hg concentration indicated an additional input of Hg to the sediment (316ngg(-1) and 10.3ngcm(-2)yr.(-)(1)), which might be due to increased human activities in the area, e.g., forest burning or mining. Our results contrast those of several paired-catchment studies that suggest a higher release of Hg from coniferous than deciduous forest, and there is a need for studies with a long-term perspective to increase our understanding of the effects of slow and gradual processes on mercury cycling. PMID- 26363143 TI - A history of early life parental loss or separation is associated with successful cognitive-behavioral therapy in major depressive disorder. AB - BACKGROUND: There is a clinical need for evidence-based psychotherapy response biomarkers in major depressive disorder (MDD). Based on previous studies, we hypothesized that lower 24-h urinary cortisol levels and a history of early life stress/trauma would predict an improved antidepressant response to cognitive behavioral therapy (CBT). METHODS: 50 currently depressed MDD subjects were enrolled. 24-h urine was collected and measured for cortisol levels by radioimmunoassay (RIA). Subjects were also administered early life stress/trauma measures at baseline: Global Perceived Early-Life Stress (GPELS), The Early Life Trauma Inventory (ELTI) and Klein Loss Scale (KLS). The efficacy of a twelve-week course of once-weekly CBT was evaluated by the primary outcome measure, the 24 item Hamilton Depression Rating Scale (HDRS24), at baseline and every four weeks, and the Beck Depression Inventory at baseline and weekly thereafter. 42 subjects had at least one complete follow-up visit (>=4 weeks of CBT), and 30 subjects completed the full 12-week course. RESULTS: Baseline 24-h urinary cortisol levels did not correlate with CBT's antidepressant response. Higher KLS scores, a measure of early life parental loss or separation, correlated with delta HDRS24 (rs=-0.39, padjusted=0.05). Complementary general linear model analysis revealed enhanced CBT efficacy in patients with a history of early life parental loss or separation [F(1,35)=6.65, p=0.01]. LIMITATIONS: Small sample size, Treatment naive population. CONCLUSIONS: Early life parental separation or loss positively correlated with CBT's antidepressant efficacy in our sample and may warrant further study in larger clinical samples. PMID- 26363146 TI - A modeling framework for characterizing near-road air pollutant concentration at community scales. AB - In this study, we combine information from transportation network, traffic emissions, and dispersion model to develop a framework to inform exposure estimates for traffic-related air pollutants (TRAPs) with a high spatial resolution. A Research LINE source dispersion model (R-LINE) is used to model multiple TRAPs from roadways at Census-block level for two U.S. regions. We used a novel Space/Time Ordinary Kriging (STOK) approach that uses data from monitoring networks to provide urban background concentrations. To reduce the computational burden, we developed and applied the METeorologically-weighted Averaging for Risk and Exposure (METARE) approach with R-LINE, where a set of selected meteorological data and annual average daily traffic (AADT) are used to obtain annual averages. Compared with explicit modeling, using METARE reduces CPU time by 88-fold (46.8h versus 32min), while still retaining accuracy of exposure estimates. We show two examples in the Piedmont region in North Carolina (~105,000 receptors) and Portland, Maine (~7000 receptors) to characterize near road air quality. Concentrations for NOx, PM2.5, and benzene in Portland drop by over 40% within 200m away from the roadway. The concentration drop in North Carolina is less than that in Portland, as previously shown in an observation based study, showing the robustness of our approach. Heavy-duty diesel vehicles (HDDV) contribute over 55% of NOx and PM2.5 near interstate highways, while light duty gasoline vehicles (LDGV) contribute over 50% of benzene to urban areas where multiple roadways intersect. Normalized mean error (NME) between explicit modeling and METARE in Portland ranges from 12.6 to 14.5% and normalized mean bias (NMB) ranges from -12.9 to -11.2%. When considering a static emission rate (i.e. the emission does not have temporal variability), both NME and NMB improved (10.5% and -9.5%). Modeled concentrations in Detroit, Michigan at an array of near-road monitors are within a factor of 2 of observed values for CO but not NOx. PMID- 26363147 TI - Bioaccessibility of lead in urban soil of Broken Hill, Australia: A study based on in vitro digestion and the IEUBK model. AB - This study was conducted to investigate lead (Pb) bioaccessibility in urban soil and to assess health risk to children in the city of Broken Hill, Australia, which was established around one of the world's largest lead-zinc-silver mines. Fifty-three topsoil (0-0.1m) and 50 subsoil (0.3-0.5m) samples were collected from earthen footpaths, nature strips, parks or vacant land throughout the urban area. The soil samples were analysed for total Pb concentration, Pb bioaccessibility and Pb mineral phases, together with important soil physicochemical properties known to influence Pb bioaccessibility. Lead bioaccessibility ranged from 24% to 89% in topsoil and from 16% to 100% in subsoil, exhibiting a generally decreasing pattern with increasing distance from the orebody. Lead bioaccessibility was strongly positively related to total Pb concentration in both the topsoil and subsoil. In subsoil, a moderate negative correlation existed between Pb bioaccessibility and soil pH, while a moderate positive correlation existed between Pb bioaccessibility and soil organic matter (OM) content. In contrast, only a weak positive correlation existed between Pb bioaccessibility and OM content in topsoil. The presence of different Pb mineral phases also appeared to have caused variation in soil Pb bioaccessibility, with galena (PbS)-rich samples tending to exhibit lower Pb bioaccessibility. The prediction of blood lead (PbB) levels in Broken Hill children aged 1-4years using the IEUBK model well matched the measured data from a recent PbB screening, suggesting a high risk of childhood chronic low-level Pb exposure (PbB levels >5MUg/dL) in Broken Hill, especially in the vicinity of the orebody. Future Pb abatement programs in Broken Hill should utilise the IEUBK model to establish target soil Pb values in an effort to achieve particular child PbB outcomes. PMID- 26363148 TI - Effects of cadmium on bioaccumulation and biochemical stress response in rice (Oryza sativa L.). AB - This study investigated the effects of various Cd concentrations on the bioaccumulation, antioxidative defense, and stress responses of rice (Oryza sativa L.). The distribution characteristics of Cd in rice were in the following order: roots>stems>grains. The bioconcentration factor values of Cd increased at concentrations lower than 3.00 mg Cd/kg and approximately decreased to a constant value at concentrations higher than 3.00 mg Cd/kg. Rice showed a higher Cd accumulation potential at low Cd concentrations than at high Cd concentrations. The Freundlich isotherm model described well the adsorption isotherms of Cd in rice roots. The biosorption mechanism of rice roots was determined to be cooperative adsorption. The malondialdehyde (MDA) content increased at a concentration range of 0.00-5.00 mg/L, indicating the enhancement of lipid peroxidation. By contrast, the MDA content slightly decreased at concentrations higher than 5.00 mg/L. Peroxidase (POD) activity exhibited active response to oxidative stress at concentrations lower than 5.00 mg/L but was inhibited at concentrations higher than 5.00 mg/L. The response to Cd stress of the N-H, O-H and C-O functional groups in rice shoots was observed via Fourier transform infrared spectroscopy. PMID- 26363149 TI - Peptide fragment of thymosin beta4 increases hippocampal neurogenesis and facilitates spatial memory. AB - Although several studies have suggested the neuroprotective effect of thymosin beta4 (TB4), a major actin-sequestering protein, on the central nervous system, little is understood regarding the action of N-acetyl-serylaspartyl-lysyl-proline (Ac-SDKP), a peptide fragment of TB4 on brain function. Here, we examined neurogenesis-stimulative effect of Ac-SDKP. Intrahippocampal infusion of Ac-SDKP facilitated the generation of new neurons in the hippocampus. Ac-SDKP-treated mouse hippocampus showed an increase in beta-catenin stability with reduction of glycogen synthase kinase-3beta (GSK-3beta) activity. Moreover, inhibition of vascular endothelial growth factor (VEGF) signaling blocked Ac-SDKP-facilitated neural proliferation. Subchronic intrahippocampal infusion of Ac-SDKP also increased spatial memory. Taken together, these data demonstrate that Ac-SDKP functions as a regulator of neural proliferation and indicate that Ac-SDKP may be a therapeutic candidate for diseases characterized by neuronal loss. PMID- 26363150 TI - Alterations in primary motor cortex neurotransmission and gene expression in hemi parkinsonian rats with drug-induced dyskinesia. AB - Treatment of Parkinson's disease (PD) with dopamine replacement relieves symptoms of poverty of movement, but often causes drug-induced dyskinesias. Accumulating clinical and pre-clinical evidence suggests that the primary motor cortex (M1) is involved in the pathophysiology of PD and that modulating cortical activity may be a therapeutic target in PD and dyskinesia. However, surprisingly little is known about how M1 neurotransmitter tone or gene expression is altered in PD, dyskinesia or associated animal models. The present study utilized the rat unilateral 6-hydroxydopamine (6-OHDA) model of PD/dyskinesia to characterize structural and functional changes taking place in M1 monoamine innervation and gene expression. 6-OHDA caused dopamine pathology in M1, although the lesion was less severe than in the striatum. Rats with 6-OHDA lesions showed a PD motor impairment and developed dyskinesia when given L-DOPA or the D1 receptor agonist, SKF81297. M1 expression of two immediate-early genes (c-Fos and ARC) was strongly enhanced by either L-DOPA or SKF81297. At the same time, expression of genes specifically involved in glutamate and GABA signaling were either modestly affected or unchanged by lesion and/or treatment. We conclude that M1 neurotransmission and signal transduction in the rat 6-OHDA model of PD/dyskinesia mirror features of human PD, supporting the utility of the model to study M1 dysfunction in PD and the elucidation of novel pathophysiological mechanisms and therapeutic targets. PMID- 26363151 TI - Interleukin-33 is released in spinal cord and suppresses experimental autoimmune encephalomyelitis in mice. AB - Interleukin-33 (IL-33) is usually expressed in the nucleus as a non-histone chromatin-associated protein. After passively released by necrotic cells, it functions as an IL-1 family member. IL-33 is highly expressed in the central nervous system (CNS), whether IL-33 is actively released in the CNS and involved in experimental autoimmune encephalomyelitis (EAE) remains unclear. In this study, we found that IL-33 and receptor ST2 were expressed in the spinal cord of naive mice. Compared to naive situation, the intracellular IL-33 was dramatically decreased and extracellular IL-33 was markedly increased in the spinal cord in the pre-onset, onset and peak stage of EAE. In the chronic stage, the reverse happened. The decrease of intracellular IL-33 was related to the activation of astrocytes and the damage of neurons in situ during EAE. Astrocytes secreted IL 33 actively upon inflammatory stimulation in vitro. Furthermore, blockage of the CNS-derived IL-33 exacerbated EAE development. Our data demonstrated that IL-33 was released by activated astrocytes actively, and by damaged neurons during EAE. It plays a suppressive role in EAE development via an autocrine or paracrine manner. Our findings are helpful to understand the release feature and function of the CNS-derived IL-33 and supply a potential therapeutic target for multiple sclerosis. PMID- 26363152 TI - Progressive irreversible hearing loss is caused by stria vascularis degeneration in an Slc26a4-insufficient mouse model of large vestibular aqueduct syndrome. AB - Hearing loss of patients with enlargement of the vestibular aqueduct (EVA) can fluctuate or progress, with overall downward progression. The most common detectable cause of EVA is mutations of SLC26A4. We previously described a transgenic Slc26a4-insufficient mouse model of EVA in which Slc26a4 expression is controlled by doxycycline administration. Mice that received doxycycline from conception until embryonic day 17.5 (DE17.5; doxycycline discontinued at embryonic day 17.5) had fluctuating hearing loss between 1 and 6 months of age with an overall downward progression after 6 months of age. In this study, we characterized the cochlear functional and structural changes underlying irreversible hearing loss in DE17.5 mice at 12 months of age. The endocochlear potential was decreased and inversely correlated with auditory brainstem response thresholds. The stria vascularis was thickened and edematous in ears with less severe hearing loss, and thinned and atrophic in ears with more severe hearing loss. There were pathologic changes in marginal cell morphology and gene expression that were not observed at 3 months. We conclude that strial dysfunction and degeneration are the primary causes of irreversible progressive hearing loss in our Slc26a4-insufficient mouse model of EVA. This model of primary strial atrophy may be used to explore the mechanisms of progressive hearing loss due to strial dysfunction. PMID- 26363153 TI - Synergistic neuroprotection by epicatechin and quercetin: Activation of convergent mitochondrial signaling pathways. AB - In view of evidence that increased consumption of epicatechin (E) and quercetin (Q) may reduce the risk of stroke, we have measured the effects of combining E and Q on mitochondrial function and neuronal survival following oxygen-glucose deprivation (OGD). Relative to mouse cortical neuron cultures pretreated (24h) with either E or Q (0.1-10MUM), E+Q synergistically attenuated OGD-induced neuronal cell death. E, Q and E+Q (0.3MUM) increased spare respiratory capacity but only E+Q (0.3MUM) preserved this crucial parameter of neuronal mitochondrial function after OGD. These improvements were accompanied by corresponding increases in cyclic AMP response element binding protein (CREB) phosphorylation and the expression of CREB-target genes that promote neuronal survival (Bcl-2) and mitochondrial biogenesis (PGC-1alpha). Consistent with these findings, E+Q (0.1 and 1.0MUM) elevated mitochondrial gene expression (MT-ND2 and MT-ATP6) to a greater extent than E or Q after OGD. Q (0.3-3.0MUM), but not E (3.0MUM), elevated cytosolic calcium (Ca(2+)) spikes and the mitochondrial membrane potential. Conversely, E and E+Q (0.1 and 0.3MUM), but not Q (0.1 and 0.3MUM), activated protein kinase B (Akt). Nitric oxide synthase (NOS) inhibition with L N(G)-nitroarginine methyl ester (1.0MUM) blocked neuroprotection by E (0.3MUM) or Q (1.0MUM). Oral administration of E+Q (75mg/kg; once daily for 5days) reduced hypoxic-ischemic brain injury. These findings suggest E and Q activate Akt- and Ca(2+)-mediated signaling pathways that converge on NOS and CREB resulting in synergistic improvements in neuronal mitochondrial performance which confer profound protection against ischemic injury. PMID- 26363155 TI - Dwindling of cardio damaging effect of isoproterenol by Punica granatum L. peel extract involve activation of nitric oxide-mediated Nrf2/ARE signaling pathway and apoptosis inhibition. AB - Punica granatum L. (Punicaceae) peel is often considered as a food waste in-spite of its high bioactive metabolite composition. Primarily it is rich in therapeutically active phenolics that act on multiple cellular sites, through diverse mechanisms. Hence, the present study was envisaged to investigate the effect of standardised peel extract of P. granatum against isoproterenol (ISO) induced myocardial infarction (MI). ISO administration at a dose of 150 mg/kg; s.c., twice at 24 h interval resulted in electrocardiographic abnormalities with increased heart weight and myocardial tissue damage signifying MI. Pretreatment with the extract at 50, 100 and 200 mg/kg; p.o., for 21 days prior to ISO intoxication (30 min prior to intoxication on day 22 and 23) attenuated the observed changes, along with increased myocardial tissue superoxide dismutase activity, reduced glutathione and nitrite levels, and decreased lipid peroxidation. The extract treated groups also showed reduced serum marker enzymes of MI, showing maximum effect at highest tested dose. Immunohistochemical studies revealed increased myocardial expression of nuclear factor erythroid 2-related factor 2 (Nrf2), endothelial nitric oxide synthase (eNOS) and Bcl-2 proteins in the extract treated groups with decreased Bax expression. From the results it can be concluded that the extract pretreatment prevents ISO-induced MI through increased myocardial expression of eNOS, leading to nitric oxide-mediated Nrf2 activation, thus upregulating antioxidant mechanisms, along with inhibition of apoptosis. PMID- 26363156 TI - Factors of Good Collaboration in Home-Based End-of-Life Care: A Questionnaire Survey of Japanese Home Care Nurses, Home Helpers, and Care Managers. AB - Good interprofessional work (IPW) is essential to provide quality home-based end of-life (EOL) care. The purpose of this study was to explore the factors of "good collaboration," as evaluated separately by home care nurses (HNs), home helpers (HHs), and care managers (CMs). The relationship was examined between their evaluation of good collaboration and their recent actual experience of interprofessional collaborative work for a home-based EOL case. The questionnaire was returned nationwide by 378 HNs, 305 HHs, and 476 CMs, and data were collected on 177 EOL cases from HNs, 84 cases from HHs, and 123 cases from CMs. Evaluation of good collaboration by HNs was associated with working with a CM with whom they had multiple collaborative experiences, the client being independent for their toileting until just before dying, and sharing information regarding the client's EOL decision with an HH 1 month before dying. Evaluation of good collaboration by HHs was associated with working at an agency that collaborated with fewer CM agencies and working at an agency that allowed staff to visit dying clients. Evaluation of good collaboration by CMs was associated only with the client being dependent for toileting. Our results highlighted the characteristics of how each professional seeks to collaborate depending on their preparedness, contexts, and resultant expectations toward other professionals when entering the IPW for home based EOL care. To promote good IPW for home-based EOL care further, professionals need to understand these differences among ourselves and try to meet others' expectations. PMID- 26363154 TI - Abnormal Brain Dynamics Underlie Speech Production in Children with Autism Spectrum Disorder. AB - A large proportion of children with autism spectrum disorder (ASD) have speech and/or language difficulties. While a number of structural and functional neuroimaging methods have been used to explore the brain differences in ASD with regards to speech and language comprehension and production, the neurobiology of basic speech function in ASD has not been examined. Magnetoencephalography (MEG) is a neuroimaging modality with high spatial and temporal resolution that can be applied to the examination of brain dynamics underlying speech as it can capture the fast responses fundamental to this function. We acquired MEG from 21 children with high-functioning autism (mean age: 11.43 years) and 21 age- and sex-matched controls as they performed a simple oromotor task, a phoneme production task and a phonemic sequencing task. Results showed significant differences in activation magnitude and peak latencies in primary motor cortex (Brodmann Area 4), motor planning areas (BA 6), temporal sequencing and sensorimotor integration areas (BA 22/13) and executive control areas (BA 9). Our findings of significant functional brain differences between these two groups on these simple oromotor and phonemic tasks suggest that these deficits may be foundational and could underlie the language deficits seen in ASD. PMID- 26363157 TI - Transnational Support of Asian Indian Elderly in India: Examining Patterns of Exchanges. AB - Using a mixed methods approach, the provision of support exchanges between family members across national borders was examined. Specifically, this project examined transnational support among Asian Indian elderly residing in India whose children resided outside India. Seventy adults participated in this project in the cities of Bangalore and Mumbai. Individuals participated in either a focus group meeting or completed a survey to examine their transnational family support experiences. Most seniors were educated, of middle-income category or higher, socially active, enjoyed good health, and were not keen to live in multigeneration households. Survey findings suggest that transnational care is reciprocal in nature and that communication technology has enhanced intergenerational contact. The older adults' report of support exchanges provided and received between generations showed significant differences on certain types of support. Undoubtedly, in today's rapidly growing global economy, a great deal of emotional support, communication, and exchanges takes place between adults and their elderly parents across national borders. PMID- 26363158 TI - Approaches to Information Sharing and Assessment: Evidence From a Demonstration Program. AB - This article categorizes and delineates approaches to information sharing and assessment in a demonstration program established by central government in England. Its purpose was to develop and test a set of principles relating to a general assessment framework for adults in demonstrator sites, maximizing the use of information technology where feasible. The method employed comprised the systematic analysis of documents associated with the funding application and a telephone interview with personnel in each site. Data were collected from 17 initiatives, 13 of which provided detailed information on information sharing within the assessment process. A taxonomy of approaches was produced and information sharing in the assessment process reported in terms of setting and personnel; approaches to data collection, storage, and transfer; and changes to the process. A classification of the initiatives within a demonstration program was a useful means of describing them. Measures of intermediate outcomes captured changes in information sharing between agencies. Local initiatives were successful in promoting electronic information sharing between health and social care agencies. PMID- 26363159 TI - A Patient-Centered Transitions Framework for Persons With Complex Chronic Conditions. AB - Hospitals are under increasing pressures by governing bodies to meet mandated performance standards and fiscal targets. As a result, hospitals are incentivized by funders to discharge patients efficiently and effectively. Gaining insight into the patient experience of discharge, as well as understanding patient needs and concerns, is prudent. Leveraging this knowledge may expedite patient discharge and potentially minimize hospital readmission rates. The purpose of this study was to better understand the discharge experiences and concerns of patients with multiple chronic diseases-a population currently understudied. In this study, qualitative survey data were analyzed from a large scale, mixed methods study that took place in 2011 at Bridgepoint Hospital, a complex continuing care and rehabilitation facility in Toronto, Canada. One hundred and sixteen patients were interviewed individually using a self-designed survey composed of open- and close-ended questions. All data pertaining to hospital discharge were extracted and examined using qualitative descriptive analysis. Key discharge concerns were related to process (next steps in the care plan, friction in the provider-patient relationship, premature discharge), consequences (relocation, impact on family, leaving the comforts and security of the hospital), and needs (availability of home care, managing daily activities, navigating the predisability home). Our findings are presented in a patient centered framework that can be used as a guide for future discharge strategies for complex patient populations. PMID- 26363160 TI - Extending borders. PMID- 26363161 TI - Endoscopic surgery for malignant sinonasal tumours: an eighteen year experience. AB - INTRODUCTION: Curative resection of malignant tumours of the skull base is increasingly undertaken endoscopically. Hitherto the diverse histology, rarity and long natural history have made it difficult to accrue statistically robust cohorts for comparison with conventional craniofacial resection. It is now possible to make such a comparison in a large personal cohort. METHOD: Data on all cases of sinonasal malignancy undergoing endoscopic resection with curative intent over an eighteen year period were collected prospectively and analysed for survival and prognostic factors. RESULTS: There were 140 cases, 68 men and 72 women, aged 20-92 years (mean 63 yrs). Follow-up ranged from 6-184 months (mean 60 months). Eighteen different histopathologies were represented with olfactory neuroblastoma (36), malignant melanoma (33) and adenocarcinoma (19) being the commonest. Additional radiotherapy was given in 95 cases and chemotherapy in 49. Overall survival is 84% at 5 years and 69% at 10 years. Overall disease-free survival was 77% at 5 years and 56% at ten. Overall and disease-free survival at 5 (and 10) years is, respectively, 97% and 90% for olfactory neuroblastoma, 79% and 68% for adenocarcinoma and 56% and 39% for malignant melanoma. CONCLUSION: These results show that endoscopic resection is an alternative to conventional craniofacial resection in selected cases. PMID- 26363162 TI - Current management of sinonasal undifferentiated carcinoma. AB - BACKGROUND: The management of sinonasal undifferentiated carcinoma (SNUC) remains unclear. Low incidence and poor outcomes make treatment standardization difficult. The objective of this study was to review the used treatment and our outcomes. METHODS: From 2001 to 2013, 17 cases of SNUC were treated at our department. Charts were reviewed for standard demographic, tumour size and extension, histological features, treatment strategies, surgical approach, adjuvant therapies, outcomes and complications. RESULTS: All patients presented with extensive local disease and 2 patients also had neck metastases. All patients were treated using a multimodality approach: 10 patients underwent surgery and postoperative chemoradiation, 1 patient was treated with surgery and adjuvant radiotherapy, 3 patients were treated with neoadjuvant chemotherapy, surgery and postoperative chemoradiation and the remaining 3 patients were treated with chemoradiotherapy. After median follow-up of 39 months 6 patients developed recurrences. The 3-year local control rate was 76% and the 5-year rate of overall survival was 58%. CONCLUSIONS: Management and outcomes of SNUC have improved due to advances in surgery and radiotherapy. Gross tumour resection followed by postoperative radiotherapy should be the standard of care in patients with SNUC. High-precision high-dose radiotherapy should be implemented to try to improve the outcomes. PMID- 26363163 TI - Exposure to odours improves olfactory function in healthy children. AB - BACKGROUND: Short-term exposure to odours, also called "olfactory training" has been shown to improve olfactory function in healthy people but also in people with olfactory loss. Aim of this single center, prospective, controlled study was to investigate the change of olfactory function following twice-daily, short-term exposure to 4 odours over a period of approximately 12 weeks. MATERIAL AND METHODS: We compared odour identification abilities and odour thresholds between an olfactory training group (TR group) and a group that did not perform such training (noTR group). Participants exposed themselves twice daily to 4 odours ("rose", "eucalyptus", "lemon", "clove"). Olfactory testing was performed before and after the training period using the "Sniffin' Sticks" test kit (odour identification plus odour thresholds). RESULTS: At baseline the two groups were not significantly different in terms of age and measures of olfactory sensitivity. The TR group performed significantly better for odour thresholds for all 4 odours compared to the noTR group after 12 weeks of olfactory training. Also, with regard to odour identification the TR group outperformed the noTR group. No significant differences were found for diary-based intensity ratings. CONCLUSION: Repeated exposure to odours seems to improve general olfactory sensitivity in children. PMID- 26363164 TI - Post-operative budesonide irrigations for patients with polyposis: a blinded, randomized controlled trial. AB - OBJECTIVE: To compare normal saline (NS) vs. NS+budesonide irrigations in post- functional endoscopic sinus surgery (FESS) patients with chronic rhinosinusitis with polyposis (CRSwNP). Currently, no evidence exists for NS+budesonide irrigation over NS irrigation alone. STUDY DESIGN: Prospective, single-blind, randomized controlled trial. METHODS: Subjects were prospectively enrolled to NS or NS+budesonide arms. Patients were evaluated at pre-operative and three post operative visits (POV): POV1 (1-2 weeks post-op), POV2 (3-8 weeks post-op), and POV3 (3-6 months post-op). Patients were evaluated by three quality of life (QOL) questionnaires (SNOT-22, RSOM-31, and RSDI) and two olfaction scores (UPSIT and the PEA test). RESULTS: Fifty patients were randomized, with 25 patients in the NS arm and 25 patients in the NS+budesonide arm. Two patients had unexpected pathology and were excluded from the study. By POV2 and POV3, patients experienced a significant improvement in all three QOL surveys, although the degree of improvement between arms was not significant up through POV3. Neither arm experienced significant olfactory improvement up through POV3. CONCLUSIONS: While both NS and NS+budesonide treatments improve QOL for post-FESS patients, neither intervention significantly increases QOL as compared to the other. Olfaction was not significantly improved in either treatment group. PMID- 26363165 TI - The effect of "Pyriform Turbinoplasty" on nasal airflow using a virtual model. AB - BACKGROUND: A new procedure, pyriform turbinoplasty, is described and nasal airflow is measured before and after this procedure in a virtual model. METHODOLOGY: Pyriform turbinoplasty is the submucosal reduction of the bone of the frontal process of the maxilla and the lacrimal bone. It opens part of the lateral margin of the nasal valve area with minimal damage to nasal mucosa. The resection of bone in this area can be extended by "nasal wall lateralization" when the lacrimal bone that joins the uncinate process behind the lacrimal duct as well as the base of the inferior turbinate and the edge of the maxilla at the rim of the pyriform aperture are removed. Nasal airflow was simulated using computational fluid dynamics and ANSYS Fluent solver. RESULTS: Analysis using fluid dynamics showed that these procedures help ventilation in the main airflow areas without substantially altering the normal pattern of airflow. CONCLUSIONS: The changes after performing a pyriform turbinoplasty seem to be an improvement when compared to the changes after inferior turbinate surgery that can misdirect the airflow largely through the inferior meatus. PMID- 26363166 TI - Reduced effect of intravenous antibiotic treatment on sinonasal markers in pulmonary inflammation. AB - BACKGROUND: Chronic bacterial rhinosinusitis is a common feature in Cystic fibrosis (CF) as mucociliary clearance in the sinonasal compartment is impaired. Aim of the present prospective study was to compare dynamics of inflammatory markers in the upper and lower airways (UAW/LAW) during systemic antibiotic therapy. METHODS: Nasal lavage and sputum of 16 CF-patients receiving an IV antibiotic treatment against Pseudomonas aeruginosa and/ or Staphylococcus aureus were collected before and during treatment (median after 7.5 days). Cytological changes, DNA concentration, and inflammatory markers interleukin (IL)-4, IL-8, IL 13 and Myeloperoxidase (MPO) were assessed in samples from both airway compartments. RESULTS: Total cell count declined significantly in LAW-samples but not in UAW. Although MPO and IL-8 decreased significantly in both airway compartments, this was considerably more pronounced for LAW (median decrease MPO: LAW=9.8-fold vs UAW=1.75-fold, respectively; IL-8: LAW=3-fold vs UAW=1.9-fold, respectively). DISCUSSION: This is the first publication demonstrating substantially lower effects of IV-antibiotic treatment on sinonasal than on pulmonary inflammatory markers. Consequently, our findings highlight limitations of systemic antibiotic treatment to control infection in the sinonasal compartment. Primarily, we attribute this to the paranasal sinus structure: these hollow organs, which in bacterial sinusitis are frequently filled with pus, mucoeceles and polyps, are not reached effectively by systemic antibiotic treatment. PMID- 26363167 TI - The influence of European legislation on the use of diagnostic test allergens for nasal allergen provocation in routine care of patients with allergic rhinitis. AB - In patients with allergic rhinitis (AR), the nasal provocation test (NPT) is the standard procedure to evaluate the clinical response of the nasal mucosa to allergens with a high specificity and sensitivity. In AR, it is the only test that really measures the response of the diseased mucosa to allergens while skin prick test and serum IgE confirm the clinical suspicion of sensitization. Moreover, it is of special relevance in the detection of patients with Local Allergic Rhinitis (LAR), where general sensitization cannot be measured. For the evaluation of therapeutic interventions, NPT has been used for the clinical monitoring of antiallergic drugs and allergen specific immunotherapy. Legislation within the European Union (EU) defines allergens used for diagnostic tests like NPT to be medicinal products according to Directive 2001/83 EC, but national law is considering these products to be medicinal devices in a number of EU countries. Thus, NPT products are governed by different legislations and therefore standards throughout the EU. In consequence, allergens used for diagnostic purposes need different registrations and Marketing Authorization by national authorities. After a transition period, regulations of EU Directives are to be implemented in national law by all member states. At the moment, most EU countries have not fully implemented these Directives, however, it can be expected that most countries will implement it and enforce their rules within the next years. This development has a tremendous impact on the availability of diagnostic allergens for NPT in Europe and will make make nasal provocation testing very difficult if not impossible. We describe the current situation of diagnostic allergens under the special legislative conditions in the EU with special focus on allergen products used for NPT and the consequences for the diagnosis of AR and LAR. PMID- 26363168 TI - Autophagy is deficient and inversely correlated with COX-2 expression in nasal polyps: a novel insight into the inflammation mechanism. AB - BACKGROUND: Nasal polyposis is characterised by persistent inflammation of the upper airways. Autophagy has been implicated in many chronic inflammatory diseases. Whether autophagy plays a role in nasal polyp (NP) inflammation is completely unknown and deserves investigation. METHODS: LC3 and COX-2 expression, the common autophagy and inflammation indicators, respectively, was analysed by immunoblotting in fresh tissues of NP and control nasal mucosa (NM). Primary cultures of NP-derived fibroblasts (NPDFs) and NMDFs were established for in vitro studies. Autophagy was induced by amino acid starvation and LC3 ectopic overexpression or inhibited by 3-methyladenine in the fibroblasts. Inflammation was induced by IL1-beta and TNF-alpha. LC3 and COX-2 expression was confirmed in NP specimens by immunohistochemistry. RESULTS: LC3 expression was decreased while COX-2 expression was significantly increased in fresh NP tissues compared with the NM control. In NMDFs and NPDFs, autophagy induction by starvation and LC3 overexpression downregulated COX-2 expression. Conversely, autophagy inhibition by 3-methyladenine enhanced COX-2 expression. However, IL1-beta and TNF-alpha had no effect on autophagy. Immunohistochemical studies on the NP specimens showed that most displayed low LC3 expression, whereas COX-2 was highly expressed in >50% of the specimens. Examination of two consecutive NP sections from the same tissue blocks revealed a negative correlation between LC3 and COX-2 expression. CONCLUSION: Autophagy is deficient in NP tissues and COX-2 is negatively regulated by autophagy in NP-derived fibroblasts. Since COX-2 is essential for the production of pro-inflammatory mediators, this study might help interpret persistent mucosal inflammation in NP. Attenuation of inflammation by restoring autophagy might be a therapeutic strategy for treating NP. PMID- 26363169 TI - Manifestation of eosinophilic granulomatosis with polyangiitis in head and neck. AB - INTRODUCTION: Besides an obvious clinical involvement of the ear, nose and throat (ENT)-region in Eosinophilic Granulomatosis with Polyangiitis (EGPA), systematic data is sparse. Only a few case series and case reports are available that particularly describe rhinological, otological or other manifestations of EGPA in the ENT-region. Therefore, the objective of this study is to systematically describe data on ENT-region involvement in a large series of EGPA patients. METHOD: EGPA patients examined in the Department of Otorhinolaryngology of the Christian-Albrechts-University of Kiel between 1990 and 2010 were included in the study. Criteria for ENT-manifestation were assigned to five subgroups (history, ENT examination, audiological and rhinological diagnostic findings and cranial MRI) and documented cumulatively. EGPA patients were examined in a standardized way based on the validated Ear Nose and Throat Activity Score (ENTAS) or its precursor, including audiological and rhinological diagnostic findings. MRI scans were analysed to further evaluate ENT involvement. RESULTS: A total of 95 EGPA patients were included in the study. In approximately 80% of them, ENT involvement was documented and the assumption of a frequent rhinological manifestation in patients with EGPA was confirmed. Moreover, the data reveals remarkable evidence for an otological manifestation. A missing correlation between the rhinological and the otological manifestation indicates an independent autoimmune-inflammatory process for this manifestation. CONCLUSION: The data of the largest monocentric study presented here confirms the hypothesis of a frequent ENT involvement in EGPA patients, in whom rhinological and otological manifestations are most common. Therefore, treatment should include long term follow-up and should be managed interdisciplinary. PMID- 26363171 TI - An evaluation of early countermeasures to reduce the risk of internal radiation exposure after the Fukushima nuclear incident in Japan. AB - After a radiation-release incident, intake of radionuclides in the initial stage immediately following the incident may be the major contributor to total internal radiation exposure for individuals in affected areas. However, evaluation of early internal contamination risk is greatly lacking. This study assessed the relationship between initial stage evacuation/indoor sheltering and internal radiation contamination levels 4 months after the 2011 Fukushima nuclear incident in Japan and estimated potential pathways of the contamination. The study population comprised 525 participants in the internal radiation screening program at Minamisoma Municipal General Hospital, 23 km north of the Fukushima nuclear plant. The analysed dataset included the results of a screening performed in July 2011, 4 months after the incident, and of a questionnaire on early-incident response behaviours, such as sheltering indoors and evacuations, completed by participants. Association between such early countermeasures and internal contamination levels of cesium-134 were assessed using Tobit multiple regression analyses. Our study shows that individuals who evacuated to areas outside Fukushima Prefecture had similar contamination levels of cesium-134 to individuals who stayed in Fukushima (relative risk: 0.86; 95% confidence interval: 0.74-0.99). Time spent outdoors had no significant relationship with contamination levels. The effects of inhalation from radiological plumes released from the nuclear plant on total internal radiation contamination might be so low as to be undetectable by the whole-body counting unit used to examine participants. Given the apparent limited effectiveness of evacuation and indoor sheltering on internal contamination, the decision to implement such early responses to a radiation-release incident should be made by carefully balancing their potential benefits and health risks. PMID- 26363170 TI - Developmental Activation of the AHR Increases Effector CD4+ T Cells and Exacerbates Symptoms in Autoimmune Disease-Prone Gnaq+/- Mice. AB - Perinatal environmental exposures are potentially important contributors to the increase in autoimmune diseases. Yet, the mechanisms by which these exposures increase self-reactive immune responses later in life are poorly understood. Autoimmune diseases require CD4(+) T cells for initiation, progression, and/or clinical symptoms; thus, developmental exposures that cause durable changes in CD4(+) T cells may play a role. Early life activation of the aryl hydrocarbon receptor (AHR) causes persistent changes in the response of CD4(+) T cells to infection later in life but whether CD4(+) T cells are affected by developmental exposure in the context of an autoimmune disease is unknown. Gnaq(+/-) mice develop symptoms of autoimmune disease similar to those measured clinically, and therefore can be used to evaluate gene-environment interactions during development on disease progression. Herein, we examined the effect of AHR activation in utero and via lactation, or solely via lactation, on disease onset and severity in adult Gnaq(+/-) offspring. Developmental activation of the AHR accelerated disease in Gnaq(+/-) mice, and this correlates with increases in effector CD4(+) T-cell populations. Increased symptom onset and cellular changes due to early life AHR activation were more evident in female Gnaq(+/-) mice compared with males. These observations suggest that developmental AHR activation by pollutants, and other exogenous ligands, may increase the likelihood that genetically predisposed individuals will develop clinical symptoms of autoimmune disease later in life. PMID- 26363172 TI - Dual indices for prioritizing investment in decentralized HIV services at Nigerian primary health care facilities. AB - Decentralizing health services, including those for HIV prevention and treatment, is one strategy for maximizing the use of limited resources and expanding treatment options; yet few methods exist for systematically identifying where investments for service expansion might be most effective, in terms of meeting needs and rapid availability of improved services. The Nigerian Government, the United States Government under the President's Emergency Plan for AIDS Relief (PEPFAR) program and other donors are expanding services for prevention of mother to-child transmission (PMTCT) of HIV to primary health care facilities in Nigeria. Nigerian primary care facilities vary greatly in their readiness to deliver HIV/AIDS services. In 2012, MEASURE Evaluation assessed 268 PEPFAR supported primary health care facilities in Nigeria and developed a systematic method for prioritizing these facilities for expansion of PMTCT services. Each assessed facility was scored based on two indices with multiple, weighted variables: one measured facility readiness to provide PMTCT services, the other measured local need for the services and feasibility of expansion. These two scores were compiled and the summary score used as the basis for prioritizing facilities for PMTCT service expansion. The rationale was that using need and readiness to identify where to expand PMTCT services would result in more efficient allocation of resources. A review of the results showed that the indices achieved the desired effect-that is prioritizing facilities with high need even when readiness was problematic and also prioritizing facilities where rapid scale-up was feasible. This article describes the development of the two part index and discusses advantages of using this approach when planning service expansion. The authors' objective is to contribute to development of methodologies for prioritizing investments in HIV, as well as other public health arenas, that should improve cost-effectiveness and strengthen services and systems in resource-limited countries. PMID- 26363173 TI - Influence of CO2 and Temperature on Metabolism and Development of Helicoverpa armigera (Noctuidae: Lepidoptera). AB - Climate change will have a major bearing on survival and development of insects as a result of increase in CO2 and temperature. Therefore, we studied the direct effects of CO2 and temperature on larval development and metabolism in cotton bollworm, Helicoverpa armigera (Hubner). The larvae were reared under a range of CO2 (350, 550, and 750 ppm) and temperature (15, 25, 35, and 45 degrees C) regimes on artificial diet. Elevated CO2 negatively affected the larval survival, larval weight, larval period, pupation, and adult emergence, but showed a positive effect on pupal weight, pupal period, and fecundity. Increase in temperature exhibited a negative effect on larval survival, larval period, pupal weights, and pupal period, but a positive effect on larval growth. Pupation and adult emergence were optimum at 25 degrees C. Elevated CO2 and temperature increased food consumption and metabolism of larvae by enhancing the activity of midgut proteases, carbohydrases (amylase and cellulase), and mitochondrial enzymes and therefore may cause more damage to crop production. Elevated CO2 and global warming will affect insect growth and development, which will change the interactions between the insect pests and their crop hosts. Therefore, there is need to gain an understanding of these interactions to develop strategies for mitigating the effects of climate change. PMID- 26363174 TI - Molecular Characterization of Six Small Heat Shock Proteins and Their Responses Under Cadmium Stress in Oxya chinensis (Orthoptera: Acridoidea). AB - Small heat shock proteins (sHSPs) have been implicated in many physiological processes and play important roles in the response to various stresses. In this study, the full-length sequences of six sHSPs: OcHSP19.1, 19.8, 20.4, 20.7, 21.1, and 23.8 were obtained from the rice grasshopper Oxya chinensis transcriptome database. The deduced amino acid sequences of the six OcsHSPs contain a typical alpha-crystallin domain, which consists of approximately 100 amino acid residues and five beta-strands. The phylogenetic analysis suggested that OcHSP23.8 was orthologous to the sHSPs of other species and that OcHSP19.1, 20.4, 20.7, and 21.1 were species specific, whereas OcHSP19.8 did not cluster closely to Orthoptera but was placed on the basal end of the cluster. Developmental stage dependent and tissue-specific expression patterns were evaluated using quantitative real-time polymerase chain reaction. The six genes were expressed in all developmental stages and showed clear tissue specificity. The cadmium acute experiment indicates that Cd(2+) can induce the six genes. However, various response patterns were observed among these genes under Cd(2+) stress conditions. OcHSP19.1, 19.8, 20.4, and 20.7 were highly induced by 2.61 mM Cd(2+) at 24 h. OcHSP23.8 was significantly upregulated by 2.61 mM Cd(2+) at 6 h. For OcHSP21.1, the highest expression levels were found after treatment with 0.87 mM Cd(2+) for 24 h, 1.74 mM Cd(2+) for 36 h, and 2.61 mM Cd(2+) for 12 h. These differential characteristics will facilitate future investigations into the physiological functions of sHSPs. PMID- 26363175 TI - Human cell structure-driven model construction for predicting protein subcellular location from biological images. AB - MOTIVATION: The systematic study of subcellular location pattern is very important for fully characterizing the human proteome. Nowadays, with the great advances in automated microscopic imaging, accurate bioimage-based classification methods to predict protein subcellular locations are highly desired. All existing models were constructed on the independent parallel hypothesis, where the cellular component classes are positioned independently in a multi-class classification engine. The important structural information of cellular compartments is missed. To deal with this problem for developing more accurate models, we proposed a novel cell structure-driven classifier construction approach (SC-PSorter) by employing the prior biological structural information in the learning model. Specifically, the structural relationship among the cellular components is reflected by a new codeword matrix under the error correcting output coding framework. Then, we construct multiple SC-PSorter-based classifiers corresponding to the columns of the error correcting output coding codeword matrix using a multi-kernel support vector machine classification approach. Finally, we perform the classifier ensemble by combining those multiple SC PSorter-based classifiers via majority voting. RESULTS: We evaluate our method on a collection of 1636 immunohistochemistry images from the Human Protein Atlas database. The experimental results show that our method achieves an overall accuracy of 89.0%, which is 6.4% higher than the state-of-the-art method. AVAILABILITY AND IMPLEMENTATION: The dataset and code can be downloaded from https://github.com/shaoweinuaa/. CONTACT: dqzhang@nuaa.edu.cn SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26363176 TI - markophylo: Markov chain analysis on phylogenetic trees. AB - SUMMARY: Continuous-time Markov chain models with finite state space are routinely used for analysis of discrete character data on phylogenetic trees. Examples of such discrete character data include restriction sites, gene family presence/absence, intron presence/absence and gene family size data. While models with constrained substitution rate matrices have been used to good effect, more biologically realistic models have been increasingly implemented in the recent literature combining, e.g., site rate variation, site partitioning, branch specific rates, allowing for non-stationary prior root probabilities, correcting for sampling bias, etc. to name a few. Here, a flexible and fast R package is introduced that infers evolutionary rates of discrete characters on a tree within a probabilistic framework. The package, markophylo, fits maximum-likelihood models using Markov chains on phylogenetic trees. The package is efficient, with the workhorse functions written in C++ and the interface in user-friendly R. AVAILABILITY AND IMPLEMENTATION: markophylo is available as a platform independent R package from the Comprehensive R Archive Network at https://cran.r project.org/web/packages/markophylo/. A vignette with numerous examples is also provided with the R package. CONTACT: udang@mcmaster.ca SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26363177 TI - CD30 cell graphs of Hodgkin lymphoma are not scale-free--an image analysis approach. AB - MOTIVATION: Hodgkin lymphoma (HL) is a type of B-cell lymphoma. To diagnose the subtypes, biopsies are taken and immunostained. The slides are scanned to produce high-resolution digital whole slide images (WSI). Pathologists manually inspect the spatial distribution of cells, but little is known on the statistical properties of cell distributions in WSIs. Such properties would give valuable information for the construction of theoretical models that describe the invasion of malignant cells in the lymph node and the intercellular interactions. RESULTS: In this work, we define and discuss HL cell graphs. We identify CD30(+) cells in HL WSIs, bringing together the fields of digital imaging and network analysis. We define special graphs based on the positions of the immunostained cells. We present an automatic analysis of complete WSIs to determine significant morphological and immunohistochemical features of HL cells and their spatial distribution in the lymph node tissue under three different medical conditions: lymphadenitis (LA) and two types of HL. We analyze the vertex degree distributions of CD30 cell graphs and compare them to a null model. CD30 cell graphs show higher vertex degrees than expected by a random unit disk graph, suggesting clustering of the cells. We found that a gamma distribution is suitable to model the vertex degree distributions of CD30 cell graphs, meaning that they are not scale-free. Moreover, we compare the graphs for LA and two subtypes of HL. LA and classical HL showed different vertex degree distributions. The vertex degree distributions of the two HL subtypes NScHL and mixed cellularity HL (MXcHL) were similar. AVAILABILITY AND IMPLEMENTATION: The CellProfiler pipeline used for cell detection is available at https://sourceforge.net/projects/cellgraphs/. CONTACT: ina.koch@bioinformatik.uni frankfurt.de SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26363178 TI - DIVAS: a centralized genetic variant repository representing 150,000 individuals from multiple disease cohorts. AB - MOTIVATION: A plethora of sequenced and genotyped disease cohorts is available to the biomedical research community, spread across many portals and represented in various formats. RESULTS: We have gathered several large studies, including GERA and GRU, and computed population- and disease-specific genetic variant frequencies. In total, our portal provides fast access to genetic variants observed in 84,928 individuals from 39 disease populations. We also include 66,335 controls, such as the 1000 Genomes and Scripps Wellderly. CONCLUSION: Combining multiple studies helps validate disease-associated variants in each underlying data set, detect potential false positives using frequencies of control populations, and identify novel candidate disease-causing alterations in known or suspected genes. AVAILABILITY AND IMPLEMENTATION: https://rvs.u.hpc.mssm.edu/divas CONTACT: rong.chen@mssm.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26363179 TI - A four-country ring test of nontarget effects of ivermectin residues on the function of coprophilous communities of arthropods in breaking down livestock dung. AB - By degrading the dung of livestock that graze on pastures, coprophilous arthropods accelerate the cycling of nutrients to maintain pasture quality. Many veterinary medicinal products, such as ivermectin, are excreted unchanged in the dung of treated livestock. These residues can be insecticidal and may reduce the function (i.e., dung-degradation) of the coprophilous community. In the present study, we used a standard method to monitor the degradation of dung from cattle treated with ivermectin. The present study was performed during a 1-yr period on pastures in Canada, France, The Netherlands, and Switzerland. Large effects of residue were detected on the coprophilous community, but degradation of dung was not significantly hampered. The results emphasize that failure to detect an effect of veterinary medicinal product residues on dung-degradation does not mean that the residues do not affect the coprophilous community. Rather, insect activity is only one of many factors that affect degradation, and these other factors may mask the nontarget effect of residues. Environ Toxicol Chem 2016;35:1953-1958. (c) 2015 SETAC. PMID- 26363180 TI - Targeting c-Met in Cancer by MicroRNAs: Potential Therapeutic Applications in Hepatocellular Carcinoma. AB - Preclinical Research Cancer is one of the world's deadliest diseases, with very low survival rates and increased occurrence in the future. Successfully developed target-based therapies have significantly changed cancer treatment. However, primary and/or acquired resistance in the tumor is a major challenge in current therapies and novel combinational therapies are required. RNA interference mediated gene inactivation, alone or in combination with other current therapies, provides novel promising therapeutics that can improve cure rate and overcome resistance mechanisms to conventional therapeutics. Hepatocyte Growth Factor/c Met signaling is one of the most frequently dysregulated pathways in human cancers and abnormal c-Met activation is correlated with poor clinical outcomes and drug resistance in hepatocellular carcinoma (HCC). In recent years, a growing number of studies have identified several inhibitors and microRNAs (miRNAs), specifically targeting c-Met in various cancers, including HCC. In this review, we discuss current knowledge regarding miRNAs, focusing on their involvement in cancer and their potential as research tools and therapeutics. Then, we focus on the potential use of c-Met targeting miRNAs for suppressing aberrant c-Met signaling in HCC treatment. PMID- 26363181 TI - To treat or not to treat: a rare case of pseudo-thrombotic thrombocytopenic purpura in a Jehovah's Witness. AB - BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is a rare microvascular occlusive disorder characterized by systemic intravascular aggregation of platelets, thrombocytopenia, and mechanical injury to red blood cells. We report a rare case of pernicious anemia presenting as TTP in a Jehovah's Witness. CASE REPORT: A 46-year-old Jehovah's Witness female presented with epigastric pain, vomiting, and diarrhea for 2 days and fatigue and paresthesias for 4 weeks. Initial laboratory evaluation showed severe anemia and thrombocytopenia with elevated total bilirubin and lactate dehydrogenase. Peripheral blood smear showed schistocytes, macroovalocytes, and hypersegmented neutrophils. TTP was suspected and plasmapheresis was offered. The patient refused it due to her religious beliefs. Due to the presence of macroovalocytes and hypersegmented neutrophils, vitamin B12 level was checked and found to be extremely low. Anti-intrinsic factor antibodies and anti-parietal cell antibodies were also positive; hence a diagnosis of pernicious anemia was established. Treatment with intramuscular vitamin B12 was initiated, which resulted in dramatic neurologic and hematologic improvement. DISCUSSION: Vitamin B12 deficiency can lead to elevated levels of homocysteine in the blood. Homocysteine can cause endothelial dysfunction, which can lead to formation of microvascular thrombi. Due to this phenomenon, vitamin B12 deficiency can rarely present with schistocytes and thrombocytopenia, which combined with other stigmata of vitamin B12 deficiency, can be misdiagnosed as TTP. PMID- 26363182 TI - Long-term elevated air [CO2 ] strengthens photosynthetic functioning and mitigates the impact of supra-optimal temperatures in tropical Coffea arabica and C. canephora species. AB - The tropical coffee crop has been predicted to be threatened by future climate changes and global warming. However, the real biological effects of such changes remain unknown. Therefore, this work aims to link the physiological and biochemical responses of photosynthesis to elevated air [CO2 ] and temperature in cultivated genotypes of Coffea arabica L. (cv. Icatu and IPR108) and Coffea canephora cv. Conilon CL153. Plants were grown for ca. 10 months at 25/20 degrees C (day/night) and 380 or 700 MUl CO2 l(-1) and then subjected to temperature increase (0.5 degrees C day(-1) ) to 42/34 degrees C. Leaf impacts related to stomatal traits, gas exchanges, C isotope composition, fluorescence parameters, thylakoid electron transport and enzyme activities were assessed at 25/20, 31/25, 37/30 and 42/34 degrees C. The results showed that (1) both species were remarkably heat tolerant up to 37/30 degrees C, but at 42/34 degrees C a threshold for irreversible nonstomatal deleterious effects was reached. Impairments were greater in C. arabica (especially in Icatu) and under normal [CO2 ]. Photosystems and thylakoid electron transport were shown to be quite heat tolerant, contrasting to the enzymes related to energy metabolism, including RuBisCO, which were the most sensitive components. (2) Significant stomatal trait modifications were promoted almost exclusively by temperature and were species dependent. Elevated [CO2 ], (3) strongly mitigated the impact of temperature on both species, particularly at 42/34 degrees C, modifying the response to supra optimal temperatures, (4) promoted higher water-use efficiency under moderately higher temperature (31/25 degrees C) and (5) did not provoke photosynthetic downregulation. Instead, enhancements in [CO2 ] strengthened photosynthetic photochemical efficiency, energy use and biochemical functioning at all temperatures. Our novel findings demonstrate a relevant heat resilience of coffee species and that elevated [CO2 ] remarkably mitigated the impact of heat on coffee physiology, therefore playing a key role in this crop sustainability under future climate change scenarios. PMID- 26363183 TI - Low but significant genetic differentiation underlies biologically meaningful phenotypic divergence in a large Atlantic salmon population. AB - Despite decades of research assessing the genetic structure of natural populations, the biological meaning of low yet significant genetic divergence often remains unclear due to a lack of associated phenotypic and ecological information. At the same time, structured populations with low genetic divergence and overlapping boundaries can potentially provide excellent models to study adaptation and reproductive isolation in cases where high-resolution genetic markers and relevant phenotypic and life history information are available. Here, we combined single nucleotide polymorphism (SNP)-based population inference with extensive phenotypic and life history data to identify potential biological mechanisms driving fine-scale subpopulation differentiation in Atlantic salmon (Salmo salar) from the Teno River, a major salmon river in Europe. Two sympatrically occurring subpopulations had low but significant genetic differentiation (FST = 0.018) and displayed marked differences in the distribution of life history strategies, including variation in juvenile growth rate, age at maturity and size within age classes. Large, late-maturing individuals were virtually absent from one of the two subpopulations, and there were significant differences in juvenile growth rates and size at age after oceanic migration between individuals in the respective subpopulations. Our findings suggest that different evolutionary processes affect each subpopulation and that hybridization and subsequent selection may maintain low genetic differentiation without hindering adaptive divergence. PMID- 26363184 TI - Stable 5-Hydroxymethylcytosine (5hmC) Acquisition Marks Gene Activation During Chondrogenic Differentiation. AB - Regulation of gene expression changes during chondrogenic differentiation by DNA methylation and demethylation is little understood. Methylated cytosines (5mC) are oxidized by the ten-eleven-translocation (TET) proteins to 5 hydroxymethylcytosines (5hmC), 5-formylcytosines (5fC), and 5-carboxylcytosines (5caC), eventually leading to a replacement by unmethylated cytosines (C), ie, DNA demethylation. Additionally, 5hmC is stable and acts as an epigenetic mark by itself. Here, we report that global changes in 5hmC mark chondrogenic differentiation in vivo and in vitro. Tibia anlagen and growth plate analyses during limb development at mouse embryonic days E 11.5, 13.5, and 17.5 showed dynamic changes in 5hmC levels in the differentiating chondrocytes. A similar increase in 5hmC levels was observed in the ATDC5 chondroprogenitor cell line accompanied by increased expression of the TET proteins during in vitro differentiation. Loss of TET1 in ATDC5 decreased 5hmC levels and impaired differentiation, demonstrating a functional role for TET1-mediated 5hmC dynamics in chondrogenic differentiation. Global analyses of the 5hmC-enriched sequences during early and late chondrogenic differentiation identified 5hmC distribution to be enriched in the regulatory regions of genes preceding the transcription start site (TSS), as well as in the gene bodies. Stable gains in 5hmC were observed in specific subsets of genes, including genes associated with cartilage development and in chondrogenic lineage-specific genes. 5hmC gains in regulatory promoter and enhancer regions as well as in gene bodies were strongly associated with activated but not repressed genes, indicating a potential regulatory role for DNA hydroxymethylation in chondrogenic gene expression. PMID- 26363185 TI - Arginine as an eluent overcomes the hindrance of monoclonal antibody quantification by dextran sulfate in protein A affinity chromatography. AB - Analytical chromatography using protein A affinity columns was employed for the fast and simple quantitative analysis of monoclonal antibodies (mAb) from suspension cultures of recombinant Chinese hamster ovary (rCHO) cells. Reliable results could not be obtained from analysis of rCHO cell culture supernatants containing dextran sulfate using elution buffers such as phosphate, glycine, or MgCl2 . These problems increased as the number of analysis and the concentration of dextran sulfate in samples increased. Arginine was identified as an alternative eluent to overcome the hindrance by dextran sulfate. When the samples contain dextran sulfate up to 100 mg/L, the elution buffer containing 0.6-1.0 M arginine at pH 3.0-3.8 is useful for the effective analysis. Reproducible results in the mAb quantification could be obtained by this developed arginine elution buffer from rCHO cell culture supernatants containing dextran sulfate. PMID- 26363186 TI - Improving Preschool Educators' Interactive Shared Book Reading: Effects of Coaching in Professional Development. AB - PURPOSE: The objective of this study was to examine the effects of coaching by speech-language pathologists on educators' interactive shared book reading, children's participation in shared reading, and children's language development. METHOD: Thirty-two educators and small groups of preschoolers were randomly assigned to experimental and comparison groups. The experimental group (n = 15) received 4 in-service workshops plus 5 individualized coaching sessions. The comparison group received only the 4 workshops. Participants were video-recorded during a shared book reading activity with a small group of children at pretest and posttest. The video recordings were transcribed and coded to yield measures of conversations, educators' questions, and children's responses. The mean length of utterances of the children's responses was also calculated. RESULTS: There were no significant Time * Group interaction effects for the number and length of shared reading conversations or for the number of participants in these conversations. However, significant Time * Group interactions were observed for the use of educators' experiential reasoning questions, children's experiential reasoning responses, and the mean length of utterances of children's responses. CONCLUSION: These results suggest that coaching increases educators' use of inferential questions, enhancing an interactive shared-reading strategy that had a direct impact on the children's quality and complexity of language. PMID- 26363187 TI - A systematic review of best practices in teaching ophthalmology to medical students. AB - Ophthalmic medical student education is a cornerstone to improving eye health care globally. We review the current state of the literature, listing barriers to potential best practices for undergraduate ophthalmology teaching and learning within medical curricula. We describe recent advances and pedagogical approaches in ophthalmic education and propose specific recommendations for further improvements and research. Future research should concentrate on developing teaching and learning innovations that may result in a more time- and resource effective models for interactive and integrated learning. As well as demonstrating that a competency-based approach results not just in better eye health, but also improvements in patient care, education, and medical care in general. By optimizing teaching available through improved evidence-based education, the ultimate goal is to increase medical students' knowledge and produce graduates who are highly trained in eye examination skills, resulting in improved patient eye care through timely diagnosis, referrals, and treatment. PMID- 26363188 TI - Stereoselective synthesis of 1beta,25-Dihydroxyvitamin D3 and its 26,27 hexadeuterated derivative. AB - A mild convergent synthesis of 1beta,25-dihydroxyvitamin D3 (3a), a metabolite of vitamin D3, and its C26,27-hexadeuterated derivative (3b) are described. The A ring and the CD-fragments are constructed from (R)-carvone and Inhoffen-Lythgoe diol, respectively. The triene system is assembled by a Pd(0)-catalyzed process, which involves an enol-triflate (A-ring fragment) and an alkenyl boronate (CD side chain fragment). Deuterium labeling is introduced at the last step of the synthesis. PMID- 26363189 TI - Dynamic spatiotemporal brain analyses using high-performance electrical neuroimaging, Part II: A step-by-step tutorial. AB - Our recently published analytic toolbox (Cacioppo et al., 2014), running under MATLAB environment and Brainstorm, offered a theoretical framework and set of validation studies for the automatic detection of event-related changes in the global pattern and global field power of electrical brain activity. Here, we provide a step-by-step tutorial of this toolbox along with a detailed description of analytical plans (aka the Chicago Electrical Neuroimaging Analytics, CENA) for the statistical analysis of brain microstate configuration and global field power in within and between-subject designs. Available CENA functions include: (1) a difference wave function; (2) a high-performance microsegmentation suite (HPMS), which consists of three specific analytic tools: (i) a root mean square error (RMSE) metric for identifying stable states and transition states across discrete event-related brain microstates; (ii) a similarity metric based on cosine distance in n dimensional sensor space to determine whether template maps for successive brain microstates differ in configuration of brain activity, and (iii) global field power (GFP) metrics for identifying changes in the overall level of activation of the brain; (3) a bootstrapping function for assessing the extent to which the solutions identified in the HPMS are robust (reliable, generalizable) and for empirically deriving additional experimental hypotheses; and (4) step-by step procedures for performing a priori contrasts for data analysis. CENA is freely available for brain data spatiotemporal analyses at https://hpenlaboratory.uchicago.edu/page/cena, with sample data, user tutorial videos, and documentation. PMID- 26363190 TI - Mechanically evoked cortical potentials: A physiological approach to assessment of anorectal sensory pathways. AB - BACKGROUND: Normal defaecation involves activation of anorectal mechanoreceptors responsive to pressure and stretch. The aim of this study was to develop selective anal and rectal mucosal light-touch stimulation suitable for measurement of cortical evoked potentials (EPs) in order to explore the sensory arm of these pathways. NEW METHOD: A novel device was manufactured to deliver selective rectal and/or anal light-touch stimulation using a shielded inter dental brush mounted on a rotating stepper motor (1Hz, 1ms, 15 degrees rotation). Resultant somatosensory EPs recorded with a 32-channel cortical multi electrode array were compared to those elicited by electrical anorectal stimulation (2mm anal plug electrode [1Hz, 1ms, 10V]). RESULTS: Eighteen anaesthetized female Wistar rats (body mass 180-250g) were studied. Electrical and mechanical stimulation provoked similar maximal response amplitudes (electrical anorectal 39.0MUV[SEM 5.5], mechanical anal 42.2MUV[8.1], mechanical rectal 45.8MUV[9.0]). Response latency was longer following mechanical stimulation (electrical anorectal 8.8ms[0.5], mechanical anal 16.4ms[1.1], mechanical rectal 18.3ms[2.5]). The extent of activated sensory cortex was smaller for mechanical stimulation. Sensory inferior rectal nerve activity was greater during anal compared to rectal mechanical in a subgroup of 4 rats. Evoked potentials were reproducible over 40min in a subgroup of 9 rats. COMPARISON WITH EXISTING METHODS: Cortical EPs are typically recorded in response to non physiological electrical stimuli. The use of a mechanical stimulus may provide a more localized physiological method of assessment. CONCLUSIONS: To the authors' knowledge these are the first selective brush-elicited anal and rectal EPs recorded in animals and provide a physiological approach to testing of anorectal afferent pathways. PMID- 26363191 TI - L-DOPA modulates cell viability through the ERK-c-Jun system in PC12 and dopaminergic neuronal cells. AB - L-DOPA causes neurotoxicity by modulating the Epac-ERK system in PC12 cells. This study investigated the effects of a single treatment with L-DOPA and multiple treatments with L-DOPA (MT-LD) on ERK1/2 and JNK1/2-c-Jun systems. In PC12 cells, a toxic L-DOPA concentration (200 MUM) induced sustained ERK1/2 and JNK1/2 phosphorylation that was inhibited by the Epac inhibitor brefeldin A, but not by the PKA inhibitor H89. This ERK1/2 and JNK1/2 phosphorylation was also inhibited by ERK1/2 (U0126) and JNK1/2 (SP600125) inhibitors, respectively, but sustained ERK1/2 phosphorylation was not affected by JNK1/2 phosphorylation. A non-toxic L DOPA concentration (20 MUM) induced c-Jun phosphorylation (Ser73) via transient ERK1/2 phosphorylation, whereas the toxic L-DOPA concentration induced c-Jun phosphorylation (Ser63) and c-Jun expression via Epac-sustained ERK1/2-JNK1/2 phosphorylation, which then enhanced cleaved caspase-3 expression. MT-LD (20 MUM) initially enhanced c-Jun phosphorylation (Ser73) (for 1-4 days), but later (5-6 days) induced c-Jun phosphorylation (Ser63) and c-Jun expression. In the 6 hydroxydopamine-lesioned rat model of Parkinson's disease, L-DOPA administration (10 mg/kg) protected against neurotoxicity through c-Jun phosphorylation (Ser73) for 1-2 weeks. However, L-DOPA administration (10 or 30 mg/kg) showed neurotoxicity through c-Jun phosphorylation (Ser63) and c-Jun expression via ERK1/2 phosphorylation for 3-4 weeks. Thus, in PC12 cells, non-toxic L-DOPA treatment maintained cell survival through c-Jun phosphorylation (Ser73). By contrast, toxic L-DOPA treatment or MT-LD (20 MUM) induced c-Jun phosphorylation (Ser63) and c-Jun expression via Epac-dependent sustained ERK1/2 and JNK1/2 phosphorylation, which subsequently led to cell death. These results were validated by those obtained after long-term L-DOPA administration in a rat model of Parkinson's disease. Our data indicate that L-DOPA causes neurotoxicity via the ERK1/2-c-Jun system in dopaminergic neuronal cells. PMID- 26363192 TI - Shanzhiside methylester, the principle effective iridoid glycoside from the analgesic herb Lamiophlomis rotata, reduces neuropathic pain by stimulating spinal microglial beta-endorphin expression. AB - Lamiophlomis rotata (L. rotata, Duyiwei) is an orally available Tibetan analgesic herb widely prescribed in China. Shanzhiside methylester (SM) is a principle effective iridoid glycoside of L. rotata and serves as a small molecule glucagon like peptide-1 (GLP-1) receptor agonist. This study aims to evaluate the signal mechanisms underlying SM anti-allodynia, determine the ability of SM to induce anti-allodynic tolerance, and illustrate the interactions between SM and morphine, or SM and beta-endorphin, in anti-allodynia and anti-allodynic tolerance. Intrathecal SM exerted dose-dependent and long-lasting (>4 h) anti allodynic effects in spinal nerve injury-induced neuropathic rats, with a maximal inhibition of 49% and a projected ED50 of 40.4 MUg. SM and the peptidic GLP-1 receptor agonist exenatide treatments over 7 days did not induce self-tolerance to anti-allodynia or cross-tolerance to morphine or beta-endorphin. In contrast, morphine and beta-endorphin induced self-tolerance and cross-tolerance to SM and exenatide. In the spinal dorsal horn and primary microglia, SM significantly evoked beta-endorphin expression, which was completely prevented by the microglial inhibitor minocycline and p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580. SM anti-allodynia was totally inhibited by the GLP-1 receptor antagonist exendin(9-39), minocycline, beta-endorphin antiserum, MU-opioid receptor antagonist CTAP, and SB203580. SM and exenatide specifically activated spinal p38 MAPK phosphorylation. These results indicate that SM reduces neuropathic pain by activating spinal GLP-1 receptors and subsequently stimulating microglial beta-endorphin expression via the p38 MAPK signaling. Stimulation of the endogenous beta-endorphin expression may be a novel and effective strategy for the discovery and development of analgesics for the long term treatment of chronic pain. PMID- 26363193 TI - Anandamide mediates cognitive judgement bias in rats. AB - In the present study, we investigated the effects of acute pharmacological manipulation of the endocannabinoid (EC) system on the valence of cognitive judgement bias of rats in the ambiguous-cue interpretation (ACI) paradigm. To accomplish this goal, after initial behavioural training, different groups of rats received single, systemic injections of the irreversible anandamide (AEA) hydrolysis inhibitor URB597, the cannabinoid receptor type 1 (CB1) inverse agonist AM251, the cannabinoid receptor type 2 (CB2) inverse agonist AM630, the combination of URB597 and AM251, and a combination of URB597 and AM630 and were subsequently tested with the ACI paradigm. We report that URB597 at a dose of 1 mg/kg significantly biased animals towards positive interpretation of the ambiguous cue and that this effect was abolished by pre-treatment with AM251 (1 mg/kg) or AM630 (1 mg/kg). The CB1 and CB2 inverse agonists administered alone (1 mg/kg) had no statistically significant effects on the interpretation of the ambiguous cue by rats. Our findings suggest involvement of the endocannabinoid system in the mediation of optimistic judgement bias. PMID- 26363194 TI - Opiorphin causes a panicolytic-like effect in rat panic models mediated by MU opioid receptors in the dorsal periaqueductal gray. AB - Reported evidence indicates that endogenous opioid peptides regulate the expression of escape behavior in rats, a panic-related defensive response, through MU-opioid receptors (MORs) in the dorsal periaqueductal gray (dPAG). These peptides are rapidly catabolized by degrading enzymes, including neutral endopeptidase (NEP) and aminopeptidase N (APN). Opiorphin is a peptide inhibitor of both NEP and APN and potentiates the action of endogenous enkephalins. This study evaluated the effects of intravenous and intra-dPAG administration of opiorphin on escape responses in the elevated T-maze and in a dPAG electrical stimulation test in rats. We also evaluated the involvement of MORs in the effects of opiorphin using the selective MOR antagonist CTOP. A dose of 2.0 mg/kg, i.v., of opiorphin impaired escape performance in both tests. Similar effects were observed with intra-dPAG administration of 5.0 nmol of opiorphin. Local pretreatment with 1.0 nmol CTOP antagonized the anti-escape effects of intra-dPAG opiorphin in both tests, as well as the effect of systemically administered opiorphin (2.0 mg/kg, i.v.) in the electrical stimulation test. These results indicate that opiorphin has an antipanic-like effect that is mediated by MORs in the dPAG. They may open new perspectives for the development of opiorphin analogues with greater bioavailability and physicochemical characteristics in the pursuit of new medications for the treatment of panic disorder. PMID- 26363195 TI - Lactobacillus plantarum vaccine vector expressing hemagglutinin provides protection against H9N2 challenge infection. AB - Hemagglutinin (HA) has been demonstrated as an effective candidate vaccine antigen against AIVs. Dendritic cell-targeting peptide (DCpep) can enhance the robustness of immune responses. The purpose of this study was to evaluate whether DCpep could enhance the immune response against H9N2 AIV when utilizing Lactobacillus plantarum NC8 (NC8) to present HA-DCpep in mouse and chicken models. To accomplish this, a mucosal vaccine of a recombinant NC8 strain expressing HA and DCpep that was constructed in a previous study was employed. Orally administered NC8-pSIP409-HA-DCpep elicited high serum titers of hemagglutination-inhibition (HI) antibodies in mice and also induced robust T cell immune responses in both mouse and chicken models. Orally administered NC8 pSIP409-HA-DCpep elicited high serum titers of hemagglutination-inhibition (HI) antibodies in mice and also induced robust T cell immune responses in both mouse and chicken models. These results revealed that recombinant L. plantarum NC8 pSIP409-HA-DCpep is an effective vaccine candidate against H9N2 AIVs. PMID- 26363196 TI - Identification and characterization of a highly pathogenic H5N1 avian influenza A virus during an outbreak in vaccinated chickens in Egypt. AB - Highly pathogenic avian influenza A (HPAI) H5N1 viruses continue to be a major veterinary and public health problem in Egypt. Continued surveillance of these viruses is necessary to devise strategies to control the spread of the virus and to monitor its evolutionary patterns. This is a report of the identification of a variant strain of HPAI H5N1 virus during an outbreak in 2010 in vaccinated chicken flocks in a poultry farm in Assiut, Egypt. Vaccination of chickens with an oil-emulsified inactivated A/chicken/Mexico/232/94 (H5N2) vaccine induced high levels of hemagglutination inhibition (HI) antibody titers reaching up to 9 log2. However, all flocks irrespective of the number of vaccine doses and the resultant HI titer levels came down with severe influenza infections. The qRT-PCR and rapid antigen test confirmed the influenza virus to be from H5N1 subtype. Sequencing of the hemagglutinin (HA) gene fragment from ten independent samples demonstrated that a single H5N1 strain was involved. This strain belonged to clade 2.2.1 and had several mutations in the receptor-binding site of the HA protein, thereby producing a variant strain of HPAI H5N1 virus which was antigenically different from the parent clade 2.2.1 virus circulating in Egypt at that time. In order to define the variability in HPAI H5N1 viruses over time in Egypt, we sequenced another H5N1 virus that was causing infections in chickens in 2014. Phylogenetic analysis revealed that both viruses had further distanced from the parent virus circulating during 2010. This study highlights that the antigenic mutations in HPAI H5N1 viruses represent a definitive challenge for the development of an effective vaccine for poultry. Overall, the results emphasize the need for continued surveillance of H5N1 outbreaks and extensive characterization of virus isolates from vaccinated and non-vaccinated poultry populations to better understand genetic changes and their implications. PMID- 26363197 TI - The functional dlt operon of Clostridium butyricum controls the D-alanylation of cell wall components and influences cell septation and vancomycin-induced lysis. AB - Clostridium butyricum is a Gram-positive bacterium involved in the development of necrotizing enterocolitis (NEC) in preterm infants. To colonize the digestive tract, components of the cell wall of C. butyricum must interact with the intestinal mucosa. The D-alanylation of cell wall components such as teichoic acids results in a net positive charge on the cell wall, which is important for many functions of Gram-positive bacteria. Notably, D-alanylation mediates resistance to antimicrobial peptides and antibiotics. Here, we show that the dlt operon of C. butyricum encodes the enzymes responsible for the D-alanylation of cell wall components and influences the surface properties of the cell wall. We show that the D-alanylation of cell wall components controls the septation of C. butyricum, which is an essential mechanism during vegetative growth. Furthermore, we find that D-alanylation is involved in the resistance of C. butyricum to some cationic antimicrobial peptides (CAMPs) and lysozyme. Finally, we show that the D alanylation of cell wall components influences vancomycin-induced lysis. PMID- 26363198 TI - Molecular determinants of thyroid hormone receptor selectivity in a series of phosphonic acid derivatives: 3D-QSAR analysis and molecular docking. AB - A mathematical study was performed on a set of phosphonic acid derivatives that are substrates for thyroid hormone receptor beta (TRbeta) and thyroid hormone receptor alpha (TRalpha), three-dimensional quantitative structure-activity relationship (3D-QSAR) models using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methods were employed to investigate the structural requirements for this series of compounds with improved activity. Some descriptors were also employed to significantly improve the performance of the derived models. The CoMFA model for TRbeta exhibited Rcv(2) of 0.612, Rpred(2) of 0.7218, whereas CoMSIA model showed Rcv(2) of 0.621, R(2)pred of 0.7358; the CoMFA model for TRalpha displayed Rcv(2) of 0.678, Rpred(2) of 0.6424, and the CoMSIA model had Rcv(2) of 0.671, Rpred(2) of 0.6932, which indicate that the constructed models are statistically significant. The derived contour maps further pointed out the regions where interactive fields may influence the activity. In order to validate the QSAR models and explore the origin of the selectivity at the amino acid level, molecular docking was developed, and the results indicate that Arg282, Arg320, Asn331, Gly332, Thr329 and His435 for TRbeta, but Ala225, Arg228, Met259, Arg262 and His381 for TRalpha, respectively are important residues. The information obtained from the QSAR models can be used in the design of more potent TR agonists. PMID- 26363199 TI - The protective effect of Trillin LPS-induced acute lung injury by the regulations of inflammation and oxidative state. AB - Inflammation response and oxidative stress have been reported to be involved in the pathogenesis of acute lung injury (ALI). Accordingly, anti-inflammatory treatment is proposed to be a possible efficient therapeutic strategy for ALI. The purpose of our present study was to evaluate the anti-inflammatory efficacy of trillin (Tr) on ALI induced by lipopolysaccharide (LPS) in mice and explore the underlying mechanism. BALB/c mice received Tr (50, 100 mg/kg) intraperitoneally 1 h prior to the intratracheal instillation of lipopolysaccharide (LPS) challenge. Pretreatment with Tr at the dose of 50, 100 mg/kg markedly ameliorated lung wet-to-dry weight (W/D) ratio, myeloperoxidase (MPO) activity and pulmonary histopathological conditions. In addition, the protective efficacy of Tr might be attributed to the down-regulations of neutrophil infiltration, malondialdehyde (MDA), inflammatory cytokines and the up regulations of super-oxide dismutase (SOD), catalase(CAT), glutathione(GSH), Glutathione Peroxidase(GSH-Px) in bronchoalveolar lavage fluid (BALF). Meanwhile, our study revealed some correlations between (NF-E2-related factor 2) Nrf2/heme oxygenase (HO)-1/nuclear factor-kappa B (NF-kappaB) pathways and the beneficial effect of Tr, as evidenced by the significant up-regulations of HO-1 and Nrf2 protein expressions as well as the down-regulations of p-NF-kappaB and p inhibitor of NF-kappaB (IkappaB) in lung tissues. Taken together, our results indicated that Tr exhibited protective effect on LPS-induced ALI by the regulations of related inflammatory events via the activations of Nrf2, HO-1 and NF-kappaB pathway. The current study indicated that Tr could be a potentially effective candidate medicine for the treatment of ALI. PMID- 26363200 TI - Acetaminophen hepatotoxicity and sterile inflammation: The mechanism of protection of Chlorogenic acid. AB - Acetaminophen hepatotoxicity is characterized by extensive necrotic cell death and a sterile inflammatory response. A recent report suggested that a therapeutic intervention with chlorogenic acid, a dietary polyphenolic compound, protects against acetaminophen-induced liver injury by inhibiting the inflammatory injury. The purpose of this letter is to discuss a number of reasons why the protective mechanism of chlorogenic acid against acetaminophen hepatotoxicity does not involve an anti-inflammatory effect and provides an alternative explanation for the observed protection. PMID- 26363201 TI - Differential sensitivity of immature and mature ventral mesencephalic neurons to rotenone induced neurotoxicity in vitro. AB - Rotenone induced neuronal toxicity in ventral mesencephalic (VM) dopaminergic (DA) neurons in culture is widely accepted as an important model for the investigation of Parkinson's disease (PD). However, little is known about developmental stage dependent toxic effects of rotenone on VM neurons in vitro. The objective of present study is to investigate the effect of rotenone on developing VM neurons at immature versus mature stages. Primary VM neurons were cultured in the absence of glial cells. Exposure of VM neurons to rotenone for 2 days induced cell death in both immature and mature neurons in a concentration dependent manner, but to a greater extent in mature neurons. While rotenone treated mature VM neurons showed alpha-synuclein aggregation and sensitivity to DA neurons, immature VM neurons exhibited only DA neuronal sensitivity but not alpha-synuclein aggregation. In addition, on rotenone treatment, enhancement of caspase-3 activity and reactive oxygen species (ROS) production were higher in mature VM neurons than in immature neurons. These results suggest that even though both mature and immature VM neurons are sensitive to rotenone, their manifestations differ from each other, with only mature VM neurons exhibiting Parkinsonian conditions. PMID- 26363202 TI - Low doses of bisphenol A stimulate the proliferation of breast cancer cells via ERK1/2/ERRgamma signals. AB - The effects and mechanisms of bisphenol A (BPA) on the development of breast cancer are still not well illustrated. The present study revealed that nanomolar BPA significantly promoted the proliferation of both estrogen receptor (ER) positive (MCF-7) and negative (SkBr3) breast cancer cells, which was confirmed by up regulation of proliferating cell nuclear antigen (PCNA) and Bcl-2. Neither ERalpha nor G-protein-coupled estrogen receptor (GPER) mediated this effect of BPA because their inhibitors had no effect on the BPA induced cell proliferation. However, silencing of estrogen related receptor gamma (ERRgamma) by its specific siRNA significantly abolished BPA induced proliferation of breast cancer cells, while si-ERRalpha had no similar effect. Moreover, nanomolar BPA up regulated the mRNA and protein levels of ERRgamma and triggered its nuclear translocation via a time dependent manner. Further studies revealed that 10(-8)M BPA obviously increased the phosphorylation of ERK1/2, while had no similar effect on the phosphorylation of JNK and p38 MAPK. Further, PD 98059, the inhibitor of ERK1/2, significantly abolished the BPA induced up regulation of ERRgamma and proliferation of breast cancer cells. Collectively, our results revealed that nanomolar BPA can trigger the proliferation of breast cancer cells via ERK1/2/ERRgamma signals. Given that nanomolar BPA has been widely detected in human tissues, the clinical relevance of BPA and breast cancer progression should be further investigated. PMID- 26363203 TI - In vitro assessment of environmental stress of persistent organic pollutants on the Indo-Pacific humpback dolphin. AB - Persistent organic pollutants (POPs) are detected ubiquitously and are linked to range of adverse health effects. The Indo-Pacific humpback dolphin inhabited the Pearl River Estuary (PRE), China, where high concentrations of POPs have been reported. This study evaluated the threats posed by POPs in the environment to the dolphin using an in vitro system. We selected BNF(beta-naphthoflavone) and four POPs (DDTs (dichlorodiphenyltrichloroethanes), CHLs(chlorides), HCHs(hexachlorocyclohexanes) and HCB(hexachlorobenzene)) which had been accumulated in the dolphin with high concentrations to treat the cultured skin fibroblast cells (ScSF cells) of the dolphin, and investigated the expression patterns of the ecological stress biomarkers CYP1A1, AHR and HSP70 in the cell line. The results showed that CYP1A1 was up-regulated after being exposed to different concentrations of BNF, DDTs and HCHs. CHLs, HCHs and HCB promoted AHR expression. HSP70 expression was increased by high concentrations of BNF and DDTs. Moreover, comet assay experiments revealed that DDTs produced higher degree of DNA damage to ScSF cells than other POPs, implying that the Indo-Pacific humpback dolphin in the PRE has been threatened by POPs accumulated in the body, especially by DDTs. Our results provided important information to assess the risk of the Indo-Pacific humpback dolphin raised by environmental POPs in vivo. PMID- 26363204 TI - A novel role of long non-coding RNAs in response to X-ray irradiation. AB - In the present study, the role of lncRNAs in response to radiation-induced DNA damage and oxidative stress were explored to improve our understanding of the biological pathways activated upon radiation-induced toxicity. The toxicity of X ray radiation on human bronchial epithelial cell lines (HBE) was determined through a dose-dependent increase in ROS production and gamma-H2AX formation and changes to lncRNA expression was observed and quantified using lncRNA-specific microarrays. 115 lncRNAs expression was increased in a dose-dependent manner following X-ray irradiation. Bioinformatic prediction algorithms determined that these lncRNAs significantly affect the p53 signaling pathway, and, more specifically, the BRCA 1 transcription factor and coding genes adjacent to BRCA 1. Our results highlight a previously uncharacterized role for lncRNAs to act via the p53-pathway in response to X-ray-induced DNA damage, and suggest lncRNAs may serve as novel indicators for radiation toxicity. PMID- 26363205 TI - Opinion of the Scientific Committee on Consumer Safety (SCCS)--Revision of the opinion on the safety of aluminium in cosmetic products. PMID- 26363206 TI - Opinion of the Scientific Committee on Consumer safety (SCCS) - Revision of the opinion on the safety of the use of titanium dioxide, nano form, in cosmetic products. PMID- 26363207 TI - Acute toxicity of sodium formononetin-3'-sulphonate (Sul-F) in Sprague-Dawley rats and Beagle dogs. AB - Sodium formononetin-3'-sulphonate (Sul-F, C16H12O7SNa), a water-soluble derivate of formononetin, provided significant neuroprotective and cardioprotective effects in vitro and in vivo. The aim of this study was to evaluate acute toxicity of Sul-F after intravenous administration in rats and dogs. Animals were intravenously administered Sul-F at the maximum dosage of 2000 mg/kg and 1000 mg/kg in rats and dogs, respectively. After treatment, rats and dogs were monitored for 14 days. Body weight, clinical signs, the hematological and biochemical findings, and pathological examination were performed. The results showed that no Sul-F related clinical signs of toxicity or mortality were observed in rats. Of note, the transient vomiting was found in dogs after Sul-F administration 15-20 min. In addition, a white crystal, non-metabolic Sul-F, was found after urine volatilization in Sul-F treated animals (rats and dogs). However, neither biochemical findings nor histopathological changes due to Sul-F treatment were found in tests. In summary, the present study results provided practical guidance for selecting a safe dosage for Sul-F further studies and clinical trials in the future. PMID- 26363208 TI - A 90-day subchronic study of rats fed lean pork from genetically modified pigs with muscle-specific expression of recombinant follistatin. AB - Because cardiovascular disease incidence has rapidly increased in recent years, people are choosing relatively healthier diets with low animal fat. A transgenic pig with low fat and a high percentage of lean meat was created in 2011; this pig overexpresses the follistatin (FST) gene. To evaluate the safety of lean pork derived from genetically modified (GM) pigs, a subchronic oral toxicity study was conducted using Sprague-Dawley rats. GM pork and non-GM pork were incorporated into the diet at levels of 3.75%, 7.5%, and 15% (w/w), and the main nutrients of the various diets were subsequently balanced. The safety of GM pork was assessed by comparison of the toxicology response variables in Sprague-Dawley rats consuming diets containing GM pork with those consuming non-GM pork. No treatment related adverse or toxic effects were observed based on an examination of the daily clinical signs, body weight, food consumption, hematology, serum biochemistry, and organ weight or based on gross and histopathological examination. The results demonstrate that GM pork is as safe for consumption as conventional pork. PMID- 26363209 TI - Height-resolved quantification of microstructure and texture in polycrystalline thin films using TEM orientation mapping. AB - A method is presented for the quantitative investigation of microstructure and texture evolution in polycrystalline thin films based on in-plane automated crystal orientation mapping in transmission electron microscopy, from the substrate up. To demonstrate the method we apply it to the example of low pressure metal-organic chemical vapor deposited ZnO layers. First, orientation mapping is applied to standard cross-section and plan-view transmission electron microscopy samples of films, illustrating how plan-view samples both reduce the occurrence of grain overlap that is detrimental to reliable orientation mapping and also improve sampling statistics compared to cross-sections. Motivated by this, orientation mapping has been combined with a double-wedge method for specimen preparation developed by Spiecker et al. (2007) [1], which creates a large area plan-view sample that traverses the film thickness. By measuring >10,000 grains in the film, the resulting data give access to grain size, orientation and misorientation distributions in function of height above the substrate within the film, which are, in turn, the inputs necessary for quantitative assessment of growth models and simulations. The orientation data are directly related to microstructural images, allowing correlation of orientations with in-plane and out-of-plane grain sizes and shapes. The spatial correlation of the entire data set gives insights into previously unnoticed growth mechanisms such as the presence of renucleation or preferred misorientations. Finally, the data set can be used to guide targeted, local studies by other transmission electron microscopy techniques. This is demonstrated by the site-specific application of nano-beam diffraction to validate the presence of coherent [2110]/(0113) twin boundaries first suggested by the orientation mapping. PMID- 26363210 TI - Relationship between removal of circumflex iliac nodes distal to the external iliac nodes and postoperative lower-extremity lymphedema in uterine cervical cancer. AB - OBJECTIVE: This study aimed to determine if there is a causal relationship between removal of the circumflex iliac nodes distal to the external iliac nodes (CINDEIN) and postoperative lower-extremity lymphedema (POLEL) after systematic lymphadenectomy in patients with cervical cancer. METHODS: A retrospective chart review was performed for all living cervical cancer patients who underwent lymphadenectomy and were managed at Hokkaido Cancer Center between 1993 and 2013. The type of lymphadenectomy gradually shifted from lymphadenectomy with removal of CINDEIN to without CINDEIN dissection during this period. The study period was divided into two phases: from 1993-2007 (first phase) and from 2008-2013 (second phase). We identified patients with POLEL. Logistic regression analysis was used to select the risk factors for POLEL. RESULTS: Implementation of CINDEIN dissection lymphadenectomy (94.0% vs. 20.6%, p<0.0001) and adjuvant radiotherapy (26.1% vs. 4.5%, p<0.0001) was significantly higher in the first phase than in the second phase. Of 398 patients evaluated, POLEL was noted in medical records of 80 (20.1%) patients with a median follow-up period of 78.0months. The occurrence rate of POLEL was significantly higher in the first phase than in the second phase (32.2% vs. 8.0%, p<0.0001), despite no change in the number of dissected lymph nodes between the two phases. Multivariate analysis showed that adjuvant radiation therapy (odds ratio=2.6, 95% confidence interval=1.4-4.8) and removal of CINDEIN (odds ratio=4.6, 95% confidence interval=2.4-9.0) were independent risk factors for POLEL. CONCLUSION: Elimination of CINDEIN dissection is helpful for reducing the incidence of POLEL. PMID- 26363211 TI - Biopsychosocial predictors of pain among women recovering from surgery for endometrial cancer. AB - OBJECTIVE: This study investigated post-surgical changes in pain among endometrial cancer patients, as well as the extent to which emotional distress and inflammatory and regulatory cytokine levels were associated with pain. METHODS: Women (N=71) who underwent surgery for endometrial cancer completed questionnaires assessing pain intensity and interference, depression, and anxiety at 1week, 4weeks, and 16weeks post-surgery. Participants also provided a blood sample for the analysis of a panel of 7 cytokines at the same time points. RESULTS: Participants showed significant declines in pain intensity and pain interference from 1week to 4weeks post-surgery, after which pain remained stable. After adjusting for time since surgery, surgery type, adjuvant therapy, disease stage, age, and BMI, mixed-effects linear regression models indicated that greater depression and anxiety were associated with both greater pain intensity and interference. Higher levels of circulating IL-6 were also correlated with greater pain intensity, but not interference. Fixed-effects linear regression models indicated that temporal variation in depression, anxiety, and IL-6 within individual patients was associated with corresponding changes in pain. Pain symptoms were maximal when anxiety, depression, and IL-6 were highest. No other cytokines were associated with changes in pain. CONCLUSION: These findings indicate that depression, anxiety, and IL-6 may exacerbate pain during the recovery period following surgery for a gynecologic malignancy. Targeting these psychological processes and the proinflammatory cytokine IL-6 in women with more severe and persistent pain may help to reduce suffering and improve post-surgical recovery. PMID- 26363212 TI - Robotic versus laparoscopic versus open surgery in morbidly obese endometrial cancer patients - a comparative analysis of total charges and complication rates. AB - OBJECTIVE: To compare the complications and charges of robotic vs. laparoscopic vs. open surgeries in morbidly obese patients treated for endometrial cancer. METHODS: Data were obtained from the Nationwide Inpatient Sample from 2011. Chi squared, Wilcoxon rank sum two-sample tests, and multivariate analyses were used for statistical analyses. RESULTS: Of 1087 morbidly obese (BMI >=40kg/m(2)) endometrial cancer patients (median age: 59years, range: 22 to 89), 567 (52%) had open surgery (OS), 98 (9%) laparoscopic (LS), and 422 (39%) robotic surgery (RS). 23% of OS, 13% of LS, and 8% of RS patients experienced an intraoperative or postoperative complication including: blood transfusions, mechanical ventilation, urinary tract injury, gastrointestinal injury, wound debridement, infection, venous thromboembolism, and lymphedema (p<0.0001). RS and LS patients were less likely to receive blood transfusions compared to OS (5% and 6% vs. 14%, respectively; p<0.0001). The median lengths of hospitalization for OS, LS, and RS patients were 4, 1, and 1days, respectively (p<0.0001). Median total charges associated with OS, LS, and RS were $39,281, $40,997, and $45,030 (p=0.037), respectively. CONCLUSIONS: In morbidly obese endometrial cancer patients, minimally invasive robotic or laparoscopic surgeries were associated with fewer complications and less days of hospitalization relative to open surgery. Compared to laparoscopic approach, robotic surgeries had comparable rates of complications but higher charges. PMID- 26363213 TI - Bisphenol A stimulates the epithelial mesenchymal transition of estrogen negative breast cancer cells via FOXA1 signals. AB - Estrogen receptor negative (ER-) breast cancer are associated with increased risks for metastasis and high rates of recurrence. Our present study revealed that nanomolar bisphenol A (BPA), a typical endocrine disrupting chemical, promoted the in vitro migration and induced mesenchymal transition (EMT) of ER breast cancer cells. PCR array revealed that BPA can down regulate 12 and up regulate 2 genes involved in regulation of signal transduction and biological pathways of breast cancer. The down regulated genes included FOXA1, which is a key determinant of endocrine response and down regulated by BPA via a time dependent manner. Silencing of FOXA1 by siRNA triggered the EMT of SkBr3 cells. While over expression of FOXA1 abolished BPA induced EMT. Further, 10(-8) M BPA significantly increased the phosphorylation of ERK1/2, p38-MAPK, and Akt in SkBr3 cells, while only PI3K/Akt inhibitor LY294002 attenuated the BPA induced down regulation of FOXA1 and E-Cadherin (E-Cad). Over expression of Akt also suppressed FOXA1 expression in SkBr3 cells. It suggested that PI3K/Akt mediated, at least partially, BPA induced EMT of ER-breast cancer cells. In summary, our data provided the first evidence that BPA can promote the EMT of ER-breast cancer cells through down regulation of FOXA1. PMID- 26363214 TI - Enhanced heme accessibility in horse heart mini-myoglobin: Insights from molecular modelling and reactivity studies. AB - Mini-myoglobin (mini-HHMb) is a fragment of horse-heart myoglobin (HHMb) considered to be the prototype of the product encoded by the central exon of the HHMb gene. For this reason, mini-HHMb has been studied extensively showing that carbonylation and oxygenation properties of the ferrous form are similar to those of the full-length protein, while kinetics and thermodynamics of azide binding to the ferric form are significantly different from those of HHMb. To analyze the structure-function relationships in mini-HHMb and the role of conformational fluctuations in ligand accessibility, the molecular model of mini-HHMb has been built and refined by molecular dynamics simulations, and analyzed in parallel with that of full length HHMb. Moreover, imidazole binding parameters of ferric mini-HHMb and HHMb have been determined. Furthermore, structural data of ferric mini-HHMb and HHMb have been correlated with the imidazole and previously determined azide binding properties. Present results indicate that, despite the extensive trimming, the heme-alpha-helices E-F substructure is essentially unaltered in mini-HHMb with respect to HHMb. However, the heme-Fe atom displays an enhanced accessibility in mini-HHMb, which may affect both ligand association and dissociation kinetics. PMID- 26363215 TI - Introduction to special issue: Neurotoxicity of brominated flame retardants and the quest for safer alternatives. PMID- 26363216 TI - Neurotoxicity and risk assessment of brominated and alternative flame retardants. AB - Brominated flame retardants (BFRs) are widely used chemicals that prevent or slow the onset and spreading of fire. Unfortunately, many of these compounds pose serious threats for human health and the environment, indicating an urgent need for safe(r) and less persistent alternative flame retardants (AFRs). As previous research identified the nervous system as a sensitive target organ, the neurotoxicity of past and present flame retardants is reviewed. First, an overview of the neurotoxicity of BFRs in humans and experimental animals is provided, and some common in vitro neurotoxic mechanisms of action are discussed. The combined epidemiological and toxicological studies clearly underline the need for replacing BFRs. Many potentially suitable AFRs are already in use, despite the absence of a full profile of their environmental behavior and toxicological properties. To prioritize the suitability of some selected halogenated and non halogenated organophosphorous flame retardants and inorganic halogen-free flame retardants, the available neurotoxic data of these AFRs are discussed. The suitability of the AFRs is rank-ordered and combined with human exposure data (serum concentrations, breast milk concentrations and house dust concentrations) and physicochemical properties (useful to predict e.g. bioavailability and persistence in the environment) for a first semi-quantitative risk assessment of the AFRs. As can be concluded from the reviewed data, several BFRs and AFRs share some neurotoxic effects and modes of action. Moreover, the available neurotoxicity data indicate that some AFRs may be suitable substitutes for BFRs. However, proper risk assessment is hampered by an overall scarcity of data, particularly regarding environmental persistence, human exposure levels, and the formation of breakdown products and possible metabolites as well as their toxicity. Until these data gaps in environmental behavioral and toxicological profiles are filled, large scale use of these chemicals should be cautioned. PMID- 26363217 TI - Intraoperative visualization of pancreatic juice leaking from the pancreatic stump in a swine model. PMID- 26363218 TI - The ADAR1 editing enzyme is encapsidated into HIV-1 virions. AB - Adenosine deaminase acting on RNA1 (ADAR1) was previously reported to affect HIV 1 replication. We report data showing that ADAR1 interacts with the HIV-1 p55 Gag protein, the major structural protein of the immature virus capsid. Furthermore, we found that the endogenous ADAR1 is incorporated into virions purified from the supernatant of primary HIV-1-infected CD4(+) T lymphocytes. Additional experiments demonstrated that the expression of the p55 Gag protein is sufficient for ADAR1 incorporation into virus-like particles (VLPs). Overall, our data originally support the evidence that ADAR1 can be part of the cell protein array uploaded in HIV-1 particles. PMID- 26363219 TI - Regulation of the tumor marker Fascin by the viral oncoprotein Tax of human T cell leukemia virus type 1 (HTLV-1) depends on promoter activation and on a promoter-independent mechanism. AB - Adult T-cell leukemia/lymphoma is a highly infiltrative neoplasia of CD4(+) T lymphocytes that occurs in about 5% of carriers infected with the deltaretrovirus human T-cell leukemia virus type 1 (HTLV-1). The viral oncoprotein Tax perturbs cellular signaling pathways leading to upregulation of host cell factors, amongst them the actin-bundling protein Fascin, an invasion marker of several types of cancer. However, transcriptional regulation of Fascin by Tax is poorly understood. In this study, we identified a triple mode of transcriptional induction of Fascin by Tax, which requires (1) NF-kappaB-dependent promoter activation, (2) a Tax-responsive region in the Fascin promoter, and (3) a promoter-independent mechanism sensitive to the Src family kinase inhibitor PP2. Thus, Tax regulates Fascin by a multitude of signals. Beyond, using Tax expressing and virus-transformed lymphocytes as a model system, our study is the first to identify the invasion marker Fascin as a novel target of PP2, an inhibitor of metastasis. PMID- 26363220 TI - Pathogenesis of Delayed Tension Intraventricular Pneumocephalus in Shunted Patient: Possible Role of Nocturnal Positive Pressure Ventilation. AB - BACKGROUND: Delayed intraventricular pneumocephalus is a very rare and potentially serious complication of ventriculoperitoneal shunt. It can occur several months or years after shunting. Its pathogenesis is unclear. We herein discuss the underlying mechanisms and particularly the possible role of positive pressure ventilation. CASE DESCRIPTION: A 60 year-old man presented with a lateral ventricle neurocytoma microsurgically resected complicated by a late onset (15 months) postoperative hydrocephalus requiring an adjustable ventriculoperitoneal (VP) shunt. One month later, the patient was diagnosed with a sleep apnea and required a continuous positive airway pressure (CPAP) device. A few weeks afterward the patient presented with headaches and alteration of consciousness. CT-Scan revealed a massive intraventricular pneumocephalus associated with a millimetric left petrous bone defect. A transient breakout of the positive ventilation and a subtemporal surgical repair of the defect led to the rapid resolution of the pneumocephalus. DISCUSSION: Delayed intraventricular pneumocephalus requires two conditions: a VP shunt and an osteodural defect. The CPAP may play an important trigger role in the pathogenesis of this complication through a ball valve mechanism. The management relies on transient suspension of the positive ventilation and the surgical repair of the identified defect with or without pressure adjustments of the valve. CONCLUSION: Intraventricular pneumocephalus is a potentially serious complication of patients with a VP shunt and receiving positive pressure ventilation. The introduction of a CPAP device must be discussed with the neurosurgeon beforehand in shunted patients. PMID- 26363221 TI - AMPK-dependent modulation of hepatic lipid metabolism by nesfatin-1. AB - The aim of this study was to characterize the mechanism by which peripheral nesfatin-1 regulates hepatic lipid metabolism. Continuous peripheral infusion of nesfatin-1 reduced adiposity and plasma levels of triglyceride and cholesterol. In mice fed high fat diet, peripheral nesfatin-1 significantly decreased hepatic steatosis measured by triglyceride content and oil red staining area and diameter. These alterations were associated with a significant reduction in lipogenesis-related transcriptional factors PPARgamma and SREBP1, as well as rate limited enzyme genes such as acaca, fasn, gpam, dgat1 and dgat2. In primary hepatocytes, nesfatin-1 inhibited both basal and oleic acid stimulated triglyceride accumulation, which was accompanied by a decrement in lipogenesis related genes and an increase in beta-oxidation-related genes. In cultured hepatocytes, nesfatin-1 increased levels of AMPK phosphorylation. Inhibition of AMPK by compound C blocked the reduction of triglyceride content elicited by nesfatin-1. Our studies demonstrate that nesfatin-1 attenuates lipid accumulation in hepatocytes by an AMPK-dependent mechanism. PMID- 26363222 TI - Corticotropin-releasing hormone (CRH) stimulates cocaine- and amphetamine regulated transcript gene (CART1) expression through CRH type 1 receptor (CRHR1) in chicken anterior pituitary. AB - Cocaine- and amphetamine-regulated transcript (CART) peptide(s) is generally viewed as neuropeptide(s) and can control food intake in vertebrates, however, our recent study revealed that CART1 peptide is predominantly expressed in chicken anterior pituitary, suggesting that cCART1 peptide is a novel pituitary hormone in chickens and its expression is likely controlled by hypothalamic factor(s). To test this hypothesis, in this study, we examined the spatial expression of CART1 in chicken anterior pituitary and investigated the effect of hypothalamic corticotropin-releasing hormone (CRH) on pituitary cCART1 expression. The results showed that: 1) CART1 is expressed in both caudal and cephalic lobes of chicken anterior pituitary, revealed by quantitative real-time PCR (qPCR), western blot and immuno-histochemical staining; 2) CRH potently stimulates cCART1 mRNA expression in cultured chick pituitary cells, as examined by qPCR, and this effect is blocked by CP154526 (and not K41498), an antagonist specific for chicken CRH type I receptor (cCRHR1), suggesting that cCRHR1 expressed on corticotrophs mediates this action; 3) the stimulatory effect of CRH on pituitary cCART1 expression is inhibited by pharmacological drugs targeting the intracellular AC/cAMP/PKA, PLC/IP3/Ca(2+), and MEK/ERK signaling pathways. This finding, together with the functional coupling of these signaling pathways to cCRHR1 expressed in CHO cells demonstrated by luciferase reporter assay systems, indicates that these intracellular signaling pathways coupled to cCRHR1 can mediate CRH action. Collectively, our present study offers the first substantial evidence that hypothalamic CRH can stimulate pituitary CART1 expression via activation of CRHR1 in a vertebrate species. PMID- 26363223 TI - Inhibition of c-Src/p38 MAPK pathway ameliorates renal tubular epithelial cells apoptosis in db/db mice. AB - Renal tubular epithelial cells (RTEC) apoptosis, which plays a key role in the pathogenesis and progression of diabetic nephropathy (DN), is believed to be contributive to the hyperglycemia-induced kidney failure, though the exact mechanisms remain elusive. In this study, we investigated how inhibition of c Src/p38 MAPK pathway would affect RTEC apoptosis. The c-Src inhibitor PP2 i.p. administered every other day for 8 weeks to diabetic db/db mice significantly reduced their kidney weights, daily urinary volumes, blood glucose, blood urea nitrogen, serum creatinine, triglyceride and urine albumin excretion, whereas deactivation of c-Src and p38 MAPK were also observed, along with decreases in both Bax/Bcl-2 ratio and cleaved caspase-3 level in the kidneys. In vitro, exposure of HK-2 cells (a human RTEC line), to high glucose (HG) promoted phosphorylation of c-Src and p38 MAPK, and subsequently, as revealed by western blotting, TUNEL assay and flow cytometry, increased cell death, which can be inhibited by PP2. Especially, a specific p38 MAPK inhibitor, SB203580, that both attenuated HG-induced c-Src activation and abrogated the expression of PPARgamma and CHOP, also reduced apoptosis. Taken together, PP2 inhibits c-Src and therefore reduces apoptosis in RTEC, which at least in part, is due to suppressed p38 MAPK activation in diabetic kidney. PMID- 26363224 TI - CMKLR1 and GPR1 mediate chemerin signaling through the RhoA/ROCK pathway. AB - Chemerin is an adipose-derived hormone that regulates immunity and energy homesotasis. To date, all known chemerin functions have been attributed to activation of the G protein-coupled receptor chemokine-like receptor-1 (CMKLR1). Chemerin is also the only known ligand for a second receptor, G protein-coupled receptor-1 (GPR1), whose signaling and function remains unknown. This study investigated the in vitro signal transduction mechanisms of CMKLR1 and GPR1 using a panel of luciferase-reporters and pathway-specific inhibitors. Herein we report the novel finding that chemerin signals through a RhoA and rho-associated protein kinase (ROCK)-dependent pathway for activation of the transcriptional regulator serum-response factor (SRF). Despite similarities in RhoA/ROCK, Galphai/o, and MAPK signaling, we also demonstrate species-specific and receptor-dependent variations in GPR1 and CMKLR1 signaling and expression of the SRF target genes EGR1, FOS and VCL. Moreover, we demonstrate that signaling through p38, Galphai/o, RhoA, and ROCK is required for chemerin-mediated chemotaxis of L1.2 lymphocytes and AGS gastric adenocarcinoma cells. These results provide, to our knowledge, the first empirical evidence that GPR1 is a functional chemerin receptor and identify RhoA/SRF as a novel chemerin-signaling axis via both CMKLR1 and GPR1. PMID- 26363226 TI - Facial affect recognition in body dysmorphic disorder versus obsessive-compulsive disorder: An eye-tracking study. AB - BACKGROUND: Body dysmorphic disorder (BDD) is characterised by repetitive behaviours and/or mental acts occurring in response to preoccupations with perceived defects or flaws in physical appearance (American Psychiatric Association, 2013). This study aimed to investigate facial affect recognition in BDD using an integrated eye-tracking paradigm. METHOD: Participants were 21 BDD patients, 19 obsessive-compulsive disorder (OCD) patients and 21 healthy controls (HC), who were age-, sex-, and IQ-matched. Stimuli were from the Pictures of Facial Affect (Ekman & Friesen, 1975), and outcome measures were affect recognition accuracy as well as spatial and temporal scanpath parameters. RESULTS: Relative to OCD and HC groups, BDD patients demonstrated significantly poorer facial affect perception and an angry recognition bias. An atypical scanning strategy encompassing significantly more blinks, fewer fixations of extended mean durations, higher mean saccade amplitudes, and less visual attention devoted to salient facial features was found. CONCLUSIONS: Patients with BDD were substantially impaired in the scanning of faces, and unable to extract affect-related information, likely indicating deficits in basic perceptual operations. PMID- 26363225 TI - Breast cancer cells: Modulation by melatonin and the ubiquitin-proteasome system- a review. AB - Melatonin inhibits human breast cancer cells stimulated with estrogen. This antiproliferative action depends on the presence of the estrogen receptor alpha (ERalpha) in the human MCF-7 cell line and is strictly dose-dependent. Since researchers concerned with melatonin and breast cancer have not considered the relevance of the ubiquitin-proteasome system to this research in this review we do so. The fact that the first breast cancer susceptibility gene to be identified, Brca1, functions as a ubiquitin ligase indicates that the ubiquitin proteasome system has a role in regulating susceptibility to breast cancer. While mutations of this gene increase the incidence of breast cancer, the wild type gene suppresses estrogen-dependent transcriptional events relying on the estrogen receptor ERalpha. Three other ubiquitin ligases, SCF(Skp2), E6AP and APC, interact directly with ERalpha at the ERE and AP-1 promoters of ERalpha target genes. Melatonin, like proteasome inhibitors, decreases estrogen-induced gene transcription. Indeed, it has been reported that melatonin specifically inhibits estrogen-induced transcription mediated by ERalpha at the ERE and AP1 gene promoters. Herein, we present a model in which the inhibitory action of melatonin on MCF-7 cells is mediated, directly or indirectly, by the ubiquitin-proteasome system. In this model ERalpha, apoptotic proteins, and cell cycle proteins, all influenced by melatonin, are substrates of key ubiquitin ligases including SCF(Skp2), E6AP, and SCF(B-TrCP). Since dysfunction of the ubiquitin-proteasome system is a risk factor for breast cancer, this model provides a context in which to test the clinical potential, and limitations, of melatonin and proteasome inhibitors. PMID- 26363228 TI - In vitro immunotoxicological effects of heavy metals on European sea bass (Dicentrarchus labrax L.) head-kidney leucocytes. AB - The knowledge about the direct effects of heavy metals on fish leucocytes is still limited. We investigate the in vitro effects of heavy metals (Cd, Hg, Pb or As) on oxidative stress, viability and innate immune parameters of head-kidney leucocytes (HKLs) from European sea bass (Dicentrarchus labrax). Production of free oxygen radicals was induced by Cd, Hg and As, mainly after 30 min of exposure. Cd and Hg promoted both apoptosis and necrosis cell death while Pb and As did only apoptosis, in all cases in a concentration-dependent manner. Moreover, expression of genes related to oxidative stress and apoptosis was significantly induced by Hg and Pb but down-regulated by As. In addition, the expression of the metallothionein A gene was up-regulated by Cd and Pb exposure though this transcript, as well as the heat shock protein 70, was down-regulated by Hg. Cd, methylmercury (MeHg) and As reduced the phagocytic ability, whereas Hg and Pb increased it. Interestingly, all the heavy metals decreased the phagocytic capacity (the number of ingested particles per cell). Leucocyte respiratory burst changed depending on the metal exposure, usually in a time- and dose-manner. Interestingly, the expression of immune-related genes was slightly affected by Cd, MeHg, As or Pb being Hg the form producing the greatest alterations, which included down-regulation of immunoglobulin M and hepcidin, as well as the up regulation of interleukin-1 beta mRNA levels. This study provides an in vitro approach for elucidating the heavy metals toxicity, and particularly the immunotoxicity, in fish leucocytes. PMID- 26363227 TI - ClC-3 deficiency prevents atherosclerotic lesion development in ApoE-/- mice. AB - BACKGROUND: Recent evidence suggested that ClC-3, encoding Cl(-) channel or Cl( )/H(+) antiporter, plays a critical role in regulation of a variety of physiological functions. However, remarkably little is known about whether ClC-3 is involved in atherosclerosis. This study aims to establish the involvement and direct role of ClC-3 in atherogenesis and underlying mechanisms by using ClC-3 and ApoE double null mice. METHODS AND RESULTS: After a 16-week western-type high fat diet, the ClC-3(+/+)ApoE(-/-) mice developed widespread atherosclerotic lesions in aorta. However, the lesion size was significantly reduced in aorta of ClC-3(-/-)ApoE(-/-) mice. Compared with the ClC-3(+/+) controls, there was significantly decreased ox-LDL binding and uptake in isolated peritoneal macrophages from ClC-3(-/-) mice. Moreover, the expression of scavenger receptor SR-A, but not CD36, was significantly decreased in both ClC-3(-/-) peritoneal macrophages and aortic lesions from ClC-3(-/-)ApoE(-/-) mice. These findings were further confirmed in ox-LDL-treated RAW264.7 macrophages, which showed that silence of ClC-3 inhibited SR-A expression, ox-LDL accumulation and foam cell formation, whereas overexpression of ClC-3 produced the opposite effects. In addition, ClC-3 siRNA significantly inhibited, whereas ClC-3 overexpression increased, the phosphorylation of JNK/p38 MAPK in ox-LDL-treated RAW264.7 foam cells. Pretreatment with JNK or p38 inhibitor abolished ClC-3-induced increase in SR-A expression and ox-LDL uptake. Finally, the increased JNK/p38 phosphorylation and SR-A expression induced by ClC-3 could be mimicked by reduction of [Cl(-)]i by low Cl(-) solution. CONCLUSIONS: Our findings demonstrated that ClC-3 deficiency inhibits atherosclerotic lesion development, possibly via suppression of JNK/p38 MAPK dependent SR-A expression and foam cell formation. PMID- 26363229 TI - Inhibition of SERPINe1 reduces rhabdoviral infections in zebrafish. AB - While exploring the molecular mechanisms behind the fin hemorrhages that follow zebrafish (Danio rerio) early infection with viral haemorrhagic septicemia virus (VHSV), we discovered that most serpin (serine protease inhibitor) gene transcripts were upregulated, except those of serpine1. Surprisingly, only SERPINe1-derived 14-mer peptide and low molecular weight drugs targeting SERPINe1 (i.e. tannic acid, EGCG, tiplaxtinin) inhibited in vitro infections not only of VHSV, but also of other fish rhabdoviruses such as infectious hematopoietic necrosis virus (IHNV) and spring viremia carp virus (SVCV). While the mechanisms that inhibited rhabdoviral infections remain speculative, these and other results suggested that SERPINEe1-derived peptide specifically targeted viral infectivity rather than virions. Practical applications might be developed from these studies since preliminary evidences showed that tannic acid could be used to reduce VHSV caused mortalities. These studies are an example of how the identification of host genes targeted by viral infections using microarrays might facilitate the identification of novel prevention drugs in aquaculture and illuminate viral infection mechanisms. PMID- 26363230 TI - Gene structure, molecular characterization and transcriptional expression of two p38 isoforms (MAPK11 and MAPK14) from rock bream (Oplegnathus fasciatus). AB - The p38 kinases are one of the four subgroups of mitogen-activated protein kinase (MAPK) superfamily which are involved in the innate immunity. The p38 subfamily that includes four members namely p38alpha (MAPK14), p38beta (MAPK11), p38gamma (MAPK12) and p38delta (MAPK13), regulates the activation of several transcription factors. In this study, a p38beta (OfMAPK11) homolog and a p38alpha (OfMAPK14) homolog of Oplegnathus fasciatus were identified at genomic level. Results clearly showed that both MAPK11 and MAPK14 are well-conserved at both genomic structural- and amino acid (aa)-levels. Genomic sequences of OfMAPK11 (~ 15.6 kb) and OfMAPK14 (~ 13.4 kb) had 12 exons. A comparison of exon-intron structural arrangement of these genes from different vertebrate lineages indicated that all the exon lengths are highly conserved, except their terminal exons. Full-length cDNAs of OfMAPK11 (3957 bp) and OfMAPK14 (2504 bp) encoded corresponding proteins of 361 aa and 360 aa, respectively. Both OfMAPK proteins harbored a Ser/Thr protein kinases catalytic domain (S_TKc domain) which includes an activation loop with a dual phosphorylation site (TGY motif) and several specific-binding sites for ATP and substrates. Molecular modeling of the activation loop and substrate binding sites of rock bream MAPKs revealed the conservation of crucial residues and their orientation in 3D space. Transcripts of OfMAPKs were ubiquitously detected in eleven tissues examined, however at different levels. The modulation of OfMAPKs' transcription upon pathogen-associated molecular patterns (PAMPs: flagellin, lipopolysaccharide and poly I:C) and pathogens (Edwardsiella tarda, Streptococcus iniae and rock bream iridovirus) was investigated. Among the seven examined tissues, the flagellin-challenge upregulated the mRNA level of both OfMAPKs in the head kidney. Meanwhile, modulation of OfMAPK mRNA expression in the liver upon other immune-challenges varied in a time-dependent manner. Collectively, these results suggest that OfMAPKs are true members of p38 subfamily, which might be induced by different immune stimuli. PMID- 26363231 TI - Characterization and expression analysis of laboratory of genetics and physiology 2 gene in sea perch, Lateolabrax japonicus. AB - LGP2 (laboratory of genetics and physiology 2) as a key component of the retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs), plays a predominant role in modulating RLRs-mediated cellular antiviral signaling during viral infection. In the present study, we cloned the LGP2 gene from the sea perch (Lateolabrax japonicus) (LjLGP2), an economically important farmed fish. The complete cDNA sequence of LjLGP2 was 2790 nt and encoded a polypeptide of 682 amino acids which contains four main structural domains: one DEAD/DEAH box helicase domain, one conserved restriction domain of bacterial type III restriction enzyme, one helicase superfamily c-terminal domain and one C-terminal domain of RIG-I, similar to most vertebrate LGP2. Subcellular localization analysis showed that LjLGP2 spanned the entire cytosol. The LjLGP2 mRNA was widespread expressed in the tested 10 tissues of healthy fish and significantly up-regulated post NNV infection. Furthermore, time course analysis showed that LjLGP2 transcripts significantly increased in the spleen, kidney and liver tissues after NNV infection. LjLGP2 mRNA expression was rapidly and significantly up-regulated in LJB cells after poly I:C stimulation and NNV infection. The present results suggest that LjLGP2 may be involved in recognization of NNV and play a role in antiviral innate immune against NNV in sea perch. PMID- 26363232 TI - Molecular diversity and evolution of defensins in the manila clam Ruditapes philippinarum. AB - Four types of defensins were identified in Manila clam and designated as Rpdef1, Rpdef2, Rpdef3 and Rpdef4, which encoded a polypeptide of 49, 46, 45 and 42 amino acids, respectively. Sequence alignments indicated that Rpdef1 shared 46.9% identity with Rpdef2, 40.8% with Rpdef3, and 34.7% with Rpdef4. Analysis of transcript polymorphism showed that Rpdef3 accounted for about 60% frequency of Rpdefs occurrence in clams from three geographic origins (Dalian, Qingdao and Hangzhou). By quantitative real-time RT-PCR (qRT-PCR) analysis, the transcripts of Rpdefs were mainly detected in hemocytes and they responded sensitively to bacterial challenge in hemocytes. Evolutionary analysis indicated that all Rpdefs were under positive selection with positively selected basic amino acid residues detected in the C-terminal regions, which perhaps have a functional relevance by modifying the charge distribution of Rpdefs. The results also showed some lineages with dN/dS > 1, suggesting positive selection pressures existed in some lineages of phylogeny tree constructed by mollusk defensins. Overall, our results suggest that Rpdefs perhaps played important roles in host defense and positive selection is the major driving force in generating high diversity of defensins in the Manila clam. PMID- 26363233 TI - Fish chemokines 14, 20 and 25: A comparative statement on computational analysis and mRNA regulation upon pathogenic infection. AB - In this study, we reported a molecular characterization of three CC chemokines namely, CsCC-Chem14, CsCC-Chem20 and CsCC-Chem25 which are were identified from the established cDNA library of striped murrel Channa striatus. Multiple sequence alignment of all the three chemokines revealed the presence of gene specific domains and motifs including small cytokine domain, IL8 like domain, receptor binding site and glycosaminoglycan (GAG) binding sites. Three dimensional structures of the chemokines under study showed an important facet on their anti microbial property. Tissue specific mRNA expression showed that the CsCC-Chem14 is highly expressed in spleen, CsCC-Chem20 in liver and CsCC-Chem25 in trunk kidney. On challenge C. striatus with oomycete fungus Aphanomyces invadans, both CsCC-Chem20 and CsCC-Chem25 showed significant (P < 0.05) up-regulation compared to CsCC-Chem14. The increase in the expression levels of CsCC-Chem20 and CsCC Chem25 due to infection showed that they are antimicrobial proteins. But considering the CsCC-Chem14 expression, it is found to be a constitutive chemokine and is involved in homeostatic function in spleen of C. striatus. C. striatus challenged with bacteria Aeromonas hydrophila also exhibited different up-regulation pattern in all the three chemokines at various time points. However, extensive studies are required to determine the functional activities of CsCC-Chem14, CsCC-Chem20 and CsCC-Chem25 in vitro and in vivo to gain more knowledge at the molecular and proteomic levels. PMID- 26363234 TI - Structural and evolutionary characteristics of fish-specific TLR19. AB - Toll-like receptors (TLRs) are important pattern recognition receptors in the innate immune system of fish. Although ten years have passed since the first identification, the systematic knowledge about fish-specific TLR19 is still far insufficient. In present study, a phylogenetic analysis showed that TLR19 belonged to family 11, and clustered with TLR20 and TLR11/12 on the evolutionary tree. TLR20 is the closest paralogue of TLR19. The ectodomain of TLR19 contains 24 leucine-rich repeat (LRR) modules. The electrostatic surface potential analysis indicated that the modeled structure of TLR19 ectodomain showed much stronger polarity on the ascending lateral surface than on the descending lateral surface. The ascending lateral surface with strong electrostatic surface potential possibly mainly participates in the ligand binding of TLR19 ectodomain. The quite small dN/dS value at the TLR19 locus showed that TLR19 was very conserved. Approximately one third codons in the coding sequence of TLR19 were subjected to significantly negative selection, whereas only 5 codons underwent significantly positive selection. Overall, these findings possibly help in deepening the understanding to fish-specific TLR19. PMID- 26363235 TI - Transcriptome immunomodulation of in-feed additives in Atlantic salmon Salmo salar infested with sea lice Caligus rogercresseyi. AB - One of the most significant threats to the Chilean salmon aquaculture industry is the ectoparasitic sea louse Caligus rogercresseyi. To cope with sea lice infestations, functional diets have become an important component in strengthening the host immune response. The aim of this study was to evaluate molecular mechanisms activated through immunostimulation by in-feed plant-derived additives in Atlantic salmon infected with sea lice. Herein, a transcriptome-wide sequencing analysis was performed from skin and head kidney tissues, evidencing that the immune response genes were the most variable after the challenge, especially in the head kidney, while other genes involved in metabolism were highly expressed individuals fed with the immunostimulants. Interestingly, defensive enzymes such as Cytochrome p450 and serpins were down-regulated in infested individuals, especially in skin tissue. Additionally, MHC-I and MHC-II genes were differentially expressed after the incorporation of the in-feed additives, giving some cues about the protection mechanisms of plant-derived compound as immunostimulants for infested salmons. This is the first published study that evaluates the transcriptomic response of sea lice-infested Atlantic salmon fed with in-feed additives. PMID- 26363236 TI - Sulfated galactans from Gracilaria fisheri bind to shrimp haemocyte membrane proteins and stimulate the expression of immune genes. AB - Previous studies demonstrated that sulfated galactans (SG) from Gracilaria fisheri (G. fisheri) exhibit immunostimulant activity in shrimp. The present study was conducted to test the hypothesis that SG stimulates signaling molecules of the immune response of shrimp by binding to receptors on the host cell membrane. Accordingly, we evaluated the ability of SG to bind to shrimp haemocytes and showed that SG bound to the shrimp haemocyte membrane (SHM), potentially to specific receptors. Furthermore, this binding was associated with an activation of immune response genes of shrimp. Data from confocal laser scanning micrographs revealed that FITC-labeled SG bound to haemocytes. Far western blot analysis demonstrated that SHM peptides, with molecular sizes of 13, 14, 15, 17, and 25 kDa, were associated with SG. Peptide sequence analysis of the isolated bands using LC-MS/MS and NCBI blast search revealed the identity of the 13, 14, and 17 kDa peptides as lipopolysaccharide and beta-1,3-glucan binding protein (LGBP). SG induced the expression of immune related genes and downstream signaling mediators of LGBP including IMD, IKKs, NF-kappaB, antimicrobial peptides (crustin and PEN-4), the antiviral immunity (dicer), and proPO system (proPO-I and proPO-II). A LGBP neutralizing assay with anti-LGBP antibody indicated a decrease in SG-induced expression of LGBP downstream signaling mediators and the immune related genes. In conclusion, this study demonstrated that the SG-stimulated immune activity in haemocytes is mediated, in part, through the LGBP, and IMD-NF-kappaB pathway. PMID- 26363237 TI - A synthetic peptide derived from the D1 domain of flagellin induced the expression of proinflammatory cytokines in fish macrophages. AB - Flagellin is the main protein component of flagellum in Gram negative and positive bacteria, and it is also the ligand that activates the Toll-like receptor 5 (TLR5) in fish and mammals. In higher vertebrates, flagellin induces the activation of the membrane-bound TLR5 (TLR5M), which promotes the expression of proinflammatory cytokines and chemokines, and other immunological functions. We have previously reported that recombinant flagellin from Vibrio anguillarum and its ND1 domain are able to upregulate the expression of genes encoding major the proinflammatory mediators in gilthead seabream and rainbow trout macrophages. Considering the key role of D1 domain of flagellin for binding to TLR5M and its immunostimulatory activity, we designed and chemically synthesized a peptide derived of this region. The effects of the synthetic peptide were evaluated in vitro using head kidney macrophages from gilthead seabream (Sparus aurata L., Perciformes, Sparidae) and rainbow trout (Oncorhynchus mykiss W., Salmoniformes, Salmonidae). In both species the expression of genes encoding the proinflammatory cytokines interleukin-1beta (IL-1beta) and tumour necrosis factor-alpha (TNF alpha), and the chemokine IL-8, was induced upon stimulation of macrophages with the D1 domain synthetic peptide. IL-1beta and IL-8 were the most upregulated genes and to a lesser extent TNF-alpha. Interestingly, however, the induction activity of the synthetic peptide was higher in gilthead seabream than in rainbow trout macrophages. The results were confirmed at the protein levels for IL-8. Collectively, these results suggest that synthetic peptide derived from flagelling could be a promising approach for the immunostimulation and vaccination of farmed fish. PMID- 26363238 TI - Do ferns and lycophytes function as medicinal plants? A study of their low representation in traditional pharmacopoeias. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Ethnobotany is becoming an important tool for understanding how traditional medical systems are organized and which variables affect their structure and dynamics. However, some phenomena observed in ethnobotanical studies led us to question whether such phenomena are real or methodological artifacts. The small proportion of ferns and lycophytes in ethnobotanical surveys of medicinal plants is one such phenomenon, and its causes should be identified using different approach levels. The present study aimed to clarify the reasons for a low representation of these two groups in studies of medicinal plants. MATERIALS AND METHODS: The present study considered the following hypotheses: 1) ferns and lycophytes are little represented in different ethnobotanical studies because of inadequate data collection methods to record these species; 2) ferns and lycophytes are little represented because of the local perception of their low therapeutic efficacy; and 3) species of ferns and lycophytes are represented in local pharmacopoeias in proportion to the size of their families. We chose rural communities from Chapada do Araripe, Northeast Brazil to test our hypotheses. Data on the medicinal plant repertoires of the communities and on the perceived therapeutic efficacy of ferns were obtained using two different methods, semi-structured interviews associated with free lists and a checklist interview, both applied to local specialists. The resulting data were analyzed differently for each test. In addition, data regarding the total flora x medicinal flora ratio were obtained with a floristic survey and accessing data banks from previous studies performed by our research team. RESULTS: All hypotheses were confirmed, showing that all three factors contributed to the low representation of these plant groups as medicinal resources. The present study showed that free-list interviews are not a good method to access traditional knowledge of medicinal ferns and lycophytes and that the use of visual stimuli can help the memory of the informants, thus making it possible to associate the perceived characteristics with plant use. The results also showed that individuals perceive these plants as inferior therapeutic resources compared to angiosperms, which contributes to knowledge of their use not being transmitted. The final result of the present study was that the distribution of medicinal fern and lycophyte species within families was consistent with the total flora x medicinal flora ratio. This result indicates that even if the most appropriate data collection method was used for the ethnobotanical survey, the number of species would not be as expressive as that of angiosperms. PMID- 26363239 TI - Multi-parameter optimization of a neutron backscattering landmine detection system. AB - A study was performed to enhance the neutron moderation and investigate the response of a landmine detection system based on measuring backscattered neutrons with a (3)He detector. Parameters affecting the system's response were simultaneously optimized to improve the sensitivity of the detection system. The optimized sensitivity of the detection system was analyzed for different horizontal and lateral positions of a landmine. PMID- 26363240 TI - Verification of Compton scattering spectrum of a 662keV photon beam scattered on a cylindrical steel target using MCNP5 code. AB - This article focuses on the possible application of a (137)Cs low-radioactive source (5mCi) and a NaI(Tl) detector for measuring the saturation thickness of solid cylindrical steel targets. In order to increase the reliability of the obtained experimental results and to verify the detector response function of Compton scattering spectrum, simulation using Monte Carlo N-particle (MCNP5) code is performed. The obtained results are in good agreement with the response functions of the simulation scattering and experimental scattering spectra. On the basis of such spectra, the saturation depth of a steel cylinder is determined by experiment and simulation at about 27mm using gamma energy of 662keV ((137)Cs) at a scattering angle of 120 degrees . This study aims at measuring the diameter of solid cylindrical objects by gamma-scattering technique. PMID- 26363241 TI - Intramedullary contrast injection in the setting of a split spinal cord. PMID- 26363242 TI - A multilobulated, pan-columnar cervical spine lesion causing myelopathy. PMID- 26363243 TI - Severe vertebra collapse due to vertebra osteonecrosis after percutaneous vertebroplasty. PMID- 26363244 TI - Entirely ossified subdural meningioma in thoracic vertebral canal. PMID- 26363245 TI - Posterior arch defect of the atlas in a patient with acute trauma. PMID- 26363246 TI - Traumatic burst fracture and dislocation of the lumbar spine with an intact neurologic function. PMID- 26363247 TI - Lumbar Paget disease with spinal stenosis and conus medullaris compression. PMID- 26363248 TI - A rare case of malignant nonfunctional retroperitoneal paraganglioma with C3 spinous process metastasis. PMID- 26363249 TI - Pelvic Ewing sarcoma: a radiologic and histopathologic correlation. PMID- 26363250 TI - The long-term outcome of lumbar fusion in the Swedish lumbar spine study. AB - BACKGROUND CONTEXT: Current literature suggests that in the long-term, fusion of the lumbar spine in chronic low back pain (CLBP) does not result in an outcome clearly better than structured conservative treatment modes. PURPOSE: This study aimed to assess the long-term outcome of lumbar fusion in CLBP, and also to assess methodological problems in long-term randomized controlled trials (RCTs). STUDY DESIGN: A prospective randomized study was carried out. PATIENT SAMPLE: A total of 294 patients (144 women and 150 men) with CLBP of at least 2 years' duration were randomized to lumbar fusion or non-specific physiotherapy. The mean follow-up time was 12.8 years (range 9-22). The follow up rate was 85%; exclusion of deceased patients resulted in a follow-up rate of 92%. OUTCOME MEASURES: Global Assessment (GA) of back pain, Oswestry Disability Index (ODI), visual analogue scale (VAS) for back and leg pain, Zung depression scale were determined. Work status, pain medication, and pain frequency were also documented. METHODS: Standardized outcome questionnaires were obtained before treatment and at long-term follow-up. To optimize control for group changers, four models of data analysis were used according to (1) intention to treat (ITT), (2) "as treated" (AT), (3) per protocol (PP), and (4) if the conservative group automatically classify group changers as unchanged or worse in GA (GCAC). The initial study was sponsored by Acromed (US$50,000-US$100,000). RESULTS: Except for the ITT model, the GA, the primary outcome measure, was significantly better for fusion. The proportion of patients much better or better in the fusion group was 66%, 65%, and 65% in the AT, PP, and GCAC models, respectively. In the conservative group, the same proportions were 31%, 37%, and 22%, respectively. However, the ODI, VAS back pain, work status, pain medication, and pain frequency were similar between the two groups. CONCLUSIONS: One can conclude that from the patient's perspective, reflected by the GA, lumbar fusion surgery is a valid treatment option in CLBP. On the other hand, secondary outcome measures such as ODI and work status, best analyzed by the PP model, indicated that substantial disability remained at long-term after fusion as well as after conservative treatment. The lack of objective outcome measures in CLBP and the cross-over problem transforms an RCT to an observational study, that is, Level 2 evidence. The discrepancy between the primary and secondary outcome measures prevents a strong conclusion on whether to recommend fusion in non-specific low back pain. PMID- 26363251 TI - Intradural calcifying pseudoneoplasm. PMID- 26363252 TI - Lentivirus technologies for modulation of the immune system. AB - Lentiviral vectors (LVV) are important tools for the treatment of immune system disorders. Integration of therapeutic genetic material into the haematopoietic stem cell compartment using LVV can mediate long-term correction of haematopoietic lineages, thereby correcting disease phenotypes. Twenty years of vector development have successfully brought LVV to the clinic, with follow up studies of clinical trials treating primary immunodeficiencies now being reported. Results have demonstrated clear improvements in the quality of life for patients with a number of conditions in the absence of the severe adverse events observed in earlier retroviral gene therapy trials. Growing interest in gene modified adoptive T cell transfer as an alternative strategy has driven further technology innovation, including characterisation of novel viral envelopes. We will also discuss the progression of gene editing technology to preclinical investigations in models of immune deficiency. PMID- 26363253 TI - Non-rigid image registration with anatomical structure constraint for assessing locoregional therapy of hepatocellular carcinoma. AB - PURPOSE: Assessing the treated region with locoregional therapy (LT) provides valuable information for predicting hepatocellular carcinoma (HCC) recurrence. The commonly used of assessment method is inefficient because it only compares two-dimensional CT images manually. In our previous work, we automatically aligned the two CT volumes to evaluate the therapeutic efficiency using registration algorithms. The non-rigid registration is applied to capture local deformation, however, it usually destroys internal structure. Taking these into consideration, this paper proposes a novel non-rigid registration approach for evaluating LT of HCC to maintain the image integrity. METHOD: In our registration algorithm, a global affine transformation combined with localized cubic B-spline is used to estimate the significant non-rigid motions of two livers. The proposed method extends a classical non-rigid registration based on mutual information (MI) that uses an anatomical structure term to constrain the local deformation. The energy function can be defined based on the total one associated with the anatomical structure and deformation information. Optimal transformation is obtained by finding the equilibrium state in which the total energy is minimized, indicating that the anatomical landmarks have found their correspondences. Thus, we can use the same transformation to automatically transform the ablative region to the optimal position. RESULTS: Registration accuracy is evaluated using the clinical data. Improved results are obtained with respect to all criteria in our proposed method (MI-LC) than those in the MI-based non-rigid registration. The landmark distance error (LDE) of MI-LC is decreased by an average of 3.93mm compared to the case of MI-based registration. Moreover, it could be found regardless of how many landmarks applied in our proposed method, a significant reduction in LDE values using registrations based on MI-LC compared with those based on MI is confirmed. CONCLUSION: Our proposed approach can guarantee the continuity, the accuracy and the smoothness of structures by constraining the anatomical features. The results clearly indicate that our method can retain the local deformation of the image. In addition, it assures the anatomical structure stability. PMID- 26363254 TI - A fast algorithm to estimate inverse consistent image transformation based on corresponding landmarks. AB - Inverse consistency is an important feature for non-rigid image transformation in medical imaging analysis. In this paper, a simple and efficient inverse consistent image transformation estimation algorithm is proposed to preserve correspondence of landmarks and accelerate convergence. The proposed algorithm estimates both the forward and backward transformations simultaneously in the way that they are inverse to each other based on the correspondence of landmarks. Instead of computing the inverse functions and the inverse consistent transformations, respectively, we combine them together, which can improve computation efficiency significantly. Moreover, radial basis functions (RBFs) based transformation is adopted in our algorithm, which can handle deformation with local or global support. Our algorithm maps one landmark to its corresponding position exactly using the forward and backward transformations. Moreover, our algorithm is employed to estimate the forward and backward transformations in robust point matching, as well to demonstrate the application of our algorithm in image registration. The experiment results of uniform grids and test images indicate the improvement of the proposed algorithm in the aspect of inverse consistency of transformations and the reduction of the computation time of the forward and the backward transformations. The performance of our algorithm applying to robust point matching is evaluated using both brain slices and lung slices. Our experiments show that by combing robust point matching with our algorithm, the registration accuracy can be improved and the smoothness of transformations can be preserved. PMID- 26363256 TI - Decentralizing conservation and diversifying livelihoods within Kanchenjunga Conservation Area, Nepal. AB - To alleviate poverty and enhance conservation in resource dependent communities, managers must identify existing livelihood strategies and the associated factors that impede household access to livelihood assets. Researchers increasingly advocate reallocating management power from exclusionary central institutions to a decentralized system of management based on local and inclusive participation. However, it is yet to be shown if decentralizing conservation leads to diversified livelihoods within a protected area. The purpose of this study was to identify and assess factors affecting household livelihood diversification within Nepal's Kanchenjunga Conservation Area Project, the first protected area in Asia to decentralize conservation. We randomly surveyed 25% of Kanchenjunga households to assess household socioeconomic and demographic characteristics and access to livelihood assets. We used a cluster analysis with the ten most common income generating activities (both on- and off-farm) to group the strategies households use to diversify livelihoods, and a multinomial logistic regression to identify predictors of livelihood diversification. We found four distinct groups of household livelihood strategies with a range of diversification that directly corresponded to household income. The predictors of livelihood diversification were more related to pre-existing socioeconomic and demographic factors (e.g., more landholdings and livestock, fewer dependents, receiving remittances) than activities sponsored by decentralizing conservation (e.g., microcredit, training, education, interaction with project staff). Taken together, our findings indicate that without direct policies to target marginalized groups, decentralized conservation in Kanchenjunga will continue to exclude marginalized groups, limiting a household's ability to diversify their livelihood and perpetuating their dependence on natural resources. PMID- 26363255 TI - Tanshinone II A, a multiple target neuroprotectant, promotes caveolae-dependent neuronal differentiation. AB - Neuron loss is one fundamental features of neurodegenerative diseases. Stimulating endogenous neurogenesis, especially neuronal differentiation, might potentially provide therapeutic effects to these diseases. In this study, tanshinone II A (TIIA), a multiple target neuroprotectant, was demonstrated to promote dose-dependent neuronal differentiation in three cell models of immortalized C17.2 neuronal stem cells, rat embryonic cortical neural stem cells (NSCs) and rat PC12 pheochromocytoma cells. In particular, TIIA exerted promising effects on NSCs even at the dose of 3 nM. In PC12 cells, TIIA activated mitogen activated protein kinase 42/44 (MAPK42/44) and its downstream transcription factor, cAMP response element-binding protein (CREB). In addition, TIIA up regulated the expressions of brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF). The MEK inhibitor and the antagonist to the receptors of NGF and BDNF could partially attenuate the differentiation effects, indicating that MAPK42/44 mediated BDNF and NGF signals were involved in TIIA's differentiation effects. Caveolin-1 (CAV-1), the major functional protein of membrane caveolae, plays critical roles in the endocytosis of exogenous materials. CAV1, which was activated by TIIA, might help TIIA transport across cell membrane to initiate its differentiation effects. It was proven by the evidences that suppressing the function of caveolin inhibited the differentiation effects of TIIA. Therefore, we concluded that TIIA promoted neuronal differentiation partially through MAPK42/44 mediated BDNF and NGF signals in a caveolae-dependent manner. PMID- 26363257 TI - Post-treatment of molasses wastewater by electrocoagulation and process optimization through response surface analysis. AB - Molasses wastewater is a high strength effluent of food industry such as distilleries, sugar and yeast production plants etc. It is characterized by a dark brown color and exhibits a high content in substances of recalcitrant nature such as melanoidins. In this study, electrocoagulation (EC) was studied as a post treatment step for biologically treated molasses wastewater with high nitrogen content obtained from a baker's yeast industry. Iron and copper electrodes were used in various forms; the influence and interaction of current density, molasses wastewater dilution, and reaction time, on COD, color, ammonium and nitrate removal rates and operating cost were studied and optimized through Box Behnken's response surface analysis. Reaction time varied from 0.5 to 4 h, current density varied from 5 to 40 mA/cm(2) and dilution from 0 to 90% (v/v expressed as water concentration). pH, conductivity and temperature measurements were also carried out during each experiment. From preliminary experiments, it was concluded that the application of aeration and sample dilution, considerably influenced the kinetics of the process. The obtained results showed that COD removal varied between 10 and 54%, corresponding to an operation cost ranging from 0.2 to 33 euro/kg COD removed. Significant removal rates were obtained for nitrogen as nitrate and ammonium (i.e. 70% ammonium removal). A linear relation of COD and ammonium to the design parameters was observed, while operation cost and nitrate removal responded in a curvilinear function. A low ratio of electrode surface to treated volume was used, associated to a low investment cost; in addition, iron wastes could be utilized as low cost electrodes i.e. iron fillings from lathes, aiming to a low operation cost due to electrodes replacement. In general, electrocoagulation proved to be an effective and low cost process for biologically treated molasses-wastewater treatment for additional removal of COD and nitrogen content and color reduction. Treated effluent samples with good quality were produced by EC, with COD, NH4-N and NO3-N concentrations of 180, 52 and 2 mg/l respectively. Response surface analysis revealed that optimized conditions could be established under moderate molasses wastewater dilution, (e.g. 45%), at 3.5 h treatment time and 33 mA/cm(2) current density. PMID- 26363258 TI - Impact of hydrodynamics on pollutant degradation and energy efficiency of VUV/UV and H2O2/UV oxidation processes. AB - The Vacuum-UV/UV process, an incipient catalyst/chemical-free advanced oxidation process (AOP), is potentially a cost-effective solution for the removal of harmful micropollutants from water. Utilizing a novel mechanistic numerical model, this work aimed to establish a thorough understanding of the degradation mechanisms in the VUV/UV process operating under continuous flow conditions, when compared with the widely applied H2O2/UV AOP. Of particular interest was the examination of the impact of flow characteristics (hydrodynamics) on the degradation efficacy of a target micropollutant during the VUV/UV and H2O2/UV AOPs. While hydroxyl radical (OH) oxidation was the dominant degradation pathway in both processes, the degradation efficacy of the VUV/UV process showed much stronger correlation with the extent of mixing in the photoreactor. Under a uniform flow regime, the degradation efficiency of the target pollutant achieved by the H2O2/UV process with 2- and 5 ppm H2O2 was greater than that provided by the VUV/UV process. Nonetheless, introduction of mixing and circulation zones to the VUV/UV reactor resulted in superior performance compared with the H2O2/UV AOP. Based on the electrical energy-per-order (EEO) analysis, incorporation of circulation zones resulted in a reduction of up to 50% in the overall energy cost of the VUV/UV AOP, while the corresponding reduction for the 5-ppm H2O2/UV system was less than 5%. Furthermore, the extent of OH scavenging of natural organic matter (NOM) on energy efficiency of the VUV/UV and H2O2/UV AOPs under continuous flow conditions was assessed using the EEO analysis. PMID- 26363259 TI - A study on the effects of different hydraulic loading rates (HLR) on pollutant removal efficiency of subsurface horizontal-flow constructed wetlands used for treatment of domestic wastewaters. AB - The research into the treatment of domestic wastewaters originating from Buyukdolluk village in Edirne Province was carried out over a 3 year experimental period. The wastewaters of the settlement were treated using a constructed wetland with subsurface horizontal flow, and the effects of different hydraulic loading levels on removal efficiency were studied. In order to achieve this goal, three equal chambers (ponds) of 300 m(2) each were constructed and planted with Phragmites australis. Each of the chambers was loaded with domestic wastewater with average flow discharge creating hydraulic loading rates of 0. m(3) day(-1) m(-2); 0.075 m(3) day(-1) m(-2) and 0.125 m(3) day(-1) m(-2), respectively. According to the results of the study, the inlet levels of the pollutant parameters with carbon origin in the water samples taken from the system entrance are high and the average values for three years are respectively: Biological Oxygen Demand, BOD5 -324.5 mg L(-1); Chemical Oxygen Demand, COD -484,0 mg L(-1); suspended solids (TSS) -147.3 mg L(-1) and Oil and Grease -0.123 mg L(-1). It was also determined that the removal rates of the system were closely dependent on the applied hydraulic loading levels and the highest removal rates of 64.9%, 62.5%, 86.3% and 80.34% for BOD5, COD, TSS and Oil and Grease, respectively, were determined in the pond with a hydraulic loading rate of 0.050 m(3) day(-1) m(-2). Lower removal of 57.9%, 55.5%, 81.4% and 74.5% for BOD5, COD, TSS and Oil and Grease were recorded in the pond with a hydraulic loading rate of 0.075 m(3) day( 1) m(-2); and these values were 49.1%, 47.8%, 70.9% and 62.1% for the pond with a hydraulic loading rate of 0.125 m(3) day(-1) m(-2). High removal rates were also recorded for the other investigated pollution parameters. PMID- 26363260 TI - Using functional traits to assess the resistance of subalpine grassland to trampling by mountain biking and hiking. AB - Functional traits reflect plant responses to disturbance, including from visitor impacts. The impacts of mountain biking and hiking on functional composition were compared using a common experimental protocol in a subalpine grassland in the Australian Alps. The overlapping cover of all species was recorded two weeks after different intensities of hiking (200 and 500 passes) and mountain biking (none, 25, 75, 200 and 500 passes). Species' functional trait data were combined with their relative cover to calculate community trait weighted means for plant height, leaf area, percentage leaf dry matter content and Specific Leaf Area (SLA). Species such as Poa fawcettiae with larger leaves and SLA but lower dry weight content of leaves were more resistant to use, with differences between bikers and hikers only apparent at the highest levels of use tested. This differs from some vegetation communities in Europe where plants with smaller leaves were more resistant to hiking. More research using functional traits may account for differences in species responses to trampling. Managers of conservation areas used for hiking and biking need to minimise off trail use by both user groups. PMID- 26363261 TI - Immobilisation of lead and zinc in contaminated soil using compost derived from industrial eggshell. AB - This study aims to evaluate the capacity of a compost obtained by co-composting of industrial eggshell (CES) to immobilise lead (Pb) and zinc (Zn) in an acidic soil contaminated by mining activities. Mature compost without eggshell (CWES) and natural eggshell (ES) were also tested as soil amendments for comparison purposes. Three different application rates were used for each material, ensuring the same quantity in terms of neutralizing capacity. Incubation experiments were conducted under controlled conditions and CO2 emissions monitored for 94 days. The environmental availability of Pb and Zn in the amended soil was assessed and bioassays were performed at the end of the incubation period. When eggshells were present, the CES compost raised the soil pH to values higher than 6 and reduced the soil mobile fraction for both Pb and Zn, in more than 95%. Soil toxicity towards Vibrio fischeri was also suppressed and environmental risk decreased to "low level". However, the immobilisation in the acid insoluble soil component was significantly achieved only for Zn. In addition, regarding soil carbon dynamics the CO2-C emissions were enhanced, mainly in the case of the highest rate of amendment. Both first order-E and parallel first order models may adequately describe the kinetic data of CO2-C cumulative release. Without eggshells, the CWES compost revealed limited effect on heavy metals immobilisation, likely due to its small capacity to correct soil acidity, at lower application rates. Using solely eggshells, the ES waste had similar outcomes when compared with CES, but at the higher application rate, CO2 emissions were enhanced with the eggshell compost due to the contribution of biotic carbon present therein. Therefore, this study points out that CES is an effective liming material and may be used for in situ remediation of contaminated soil with Pb and Zn. PMID- 26363262 TI - Selective autocatalytic reduction of NO from sintering flue gas by the hot sintered ore in the presence of NH3. AB - In this paper, the selective autocatalytic reduction of NO by NH3 combined with multi-metal oxides in the hot sintered ore was studied, and the catalytic activity of the hot sintered ore was investigated as a function of temperature, NH3/NO ratio, O2 content, H2O and SO2. The experimental results indicated that the hot sintered ore, when combined with NH3, had a maximum denitration efficiency of 37.67% at 450 degrees C, 3000 h(-1) gas hourly space velocity (GHSV) and a NH3/NO ratio of 0.4/1. Additionally, it was found that O2 played an important role in removing NOx. However, high O2 content had a negative effect on NO reduction. H2O was found to promote the denitration efficiency in the absence of SO2, while SO2 inhibited the catalytic activity of the sintered ore. In the presence of H2O and SO2, the catalytic activity of the sintered ore was dramatically suppressed. PMID- 26363263 TI - Prevalence of fibromyalgia and co-morbid bipolar disorder: A systematic review and meta-analysis. AB - BACKGROUND: Fibromyalgia (FM) is a chronic disorder with high morbidity and significant health service utilization costs. Few studies have reported on the phenotypic overlap of FM and bipolar disorder (BD). The aim of this review is to qualitatively and quantitatively summarize the results and clinical implications of the extant literature on the co-occurrence of FM and BD. METHODS: A systematic search of PubMed/Medline, Cochrane, PsycINFO, CINAHL and Embase was conducted to search for relevant articles. Articles were included if incidence and/or prevalence of BD was determined in the FM sample. Results of prevalence were pooled from all studies. Pooled odds ratio (OR) was calculated based on case control studies using standard meta-analytic methods. RESULTS: A total of nine studies were included. The pooled rate of BD comorbidity in samples of FM patients was 21% (n=678); however, results varied greatly as a function of study methodology. Case-controlled studies revealed a pooled OR of 7.55 of BD co morbidity in samples of FM patients [95% Confidence Interval (CI)=3.9-14.62, FM n=268, controls n=413] with low heterogeneity (I(2)=0%). LIMITATIONS: The current study was limited by the low number of available studies and heterogeneity of study methods and results. CONCLUSIONS: These data strongly suggest an association between BD and FM. Future studies employing a validated diagnostic screen are needed in order to more accurately determine the prevalence of BD in FM. An adequate psychiatric assessment is recommended in FM patients with suspected symptoms consistent with BD prior to administration of antidepressants in the treatment of FM. PMID- 26363264 TI - Circadian preference links to depression in general adult population. AB - BACKGROUND: Preference to time the daily activities towards the evening hours has been associated with a greater likelihood for depression in earlier studies consisting of relatively small samples. METHODS: In the current study, we analyzed the relationship between chronotype and depression using a combined population-based sample of 10,503 Finnish adults aged 25 to 74 years from the two national FINRISK 2007 and 2012 health examination studies. RESULTS: Our results confirmed that eveningness was significantly associated with the increased odds for a diagnosed depressive disorder, antidepressant medication, and depressive symptoms (p<0.0001 for each), after controlling for a range of depression attributed and potential confounding factors. Regardless of depressive symptoms, Evening-types had lower systolic and diastolic blood pressures, a smaller waist circumference, and a lower body weight than other chronotypes. LIMITATIONS: A limitation to our study is that the assessment of chronotype and information about depression was based on the self-report information only. However, the big population-based sample, which is derived from a national health examination survey, is a major strength of our study. CONCLUSIONS: In conclusion, our study is in line the results from the previous, smaller sample size studies confirming that Evening-types have higher risk for depression than other chronotypes. This risk is elevated even among those Evening-types with sufficient amount of sleep. PMID- 26363265 TI - Exploring trajectories of diabetes distress in adults with type 2 diabetes; a latent class growth modeling approach. AB - BACKGROUND: Moderate to severe diabetes distress (DD) is a common comorbidity among adults with type 2 diabetes. Cross-sectional studies find DD is strongly correlated with poor diabetes management, however little is known about the pattern of change of DD symptoms over long periods of time. We sought to identify and describe a set of distinct longitudinal trajectories of DD over 4 years of follow-up time. METHODS: We used data derived from the Evaluation of Diabetes Treatment study (2011-2014), a longitudinal community-based survey of Canadian adults (40-75 years) with type 2 diabetes (n=1135). To determine the number and shape of trajectories, we used a latent class growth modeling approach. RESULTS: Five distinct trajectories of DD were identified. Trajectories 1 and 2 comprised participants with persistently low (61%) or persistently low, but at risk (22%) levels of distress. Trajectory 3 (7.5%) included participants with decreasing moderate levels of distress. Trajectory 4 (6.5%) consisted of participants with increasing moderate levels of distress. Trajectory 5 (2.4%) included participants with persistently severe levels of distress. LIMITATIONS: Different populations may produce different DD trajectories and thus the generalizability of the strata identified in this report remains to be investigated. Future research is needed to determine the extent to which time-varying covariates might alter the path of DD trajectories. CONCLUSIONS: For most individuals, DD is a fairly stable condition over 4 years of follow-up time. However, for a subset of individuals, DD symptoms worsened over time. Medical health professionals might consider repeated screenings for DD in adults with type 2 diabetes. PMID- 26363266 TI - Psychomotor retardation is linked to frontal alpha asymmetry in major depression. AB - BACKGROUND: Psychomotor disturbances are a main clinical feature of major depressive disorder (MDD) but little is known about their EEG signature. One of the most replicated EEG findings in MDD is resting frontal asymmetry in the alpha band (FAA), which is thought to be a correlate of withdrawal behavior and reduced approach motivation. The purpose of this study was to assess psychomotor alterations, alpha band power, FAA and investigate the association between them. METHODS: 20 MDD patients and 19 healthy subjects were enrolled. Alpha power and FAA scores were calculated from a resting state EEG. Wrist actigraphy was recorded from the non-dominant arm for 24 h and activity level scores (AL) were extrapolated from the wakeful periods. RESULTS: MDD patients had a left lateralized frontal alpha activity and lower AL scores when compared to healthy subjects. A significant correlation was found between mean FAA and AL scores. A negative covariance between power in the lower alpha range and AL scores over the motor cortex bilaterally was detected. LIMITATIONS: Relatively small sample size. Patients were pharmacologically treated with antidepressants. CONCLUSIONS: This study replicates the finding of left-lateralized FAA and lower AL scores in MDD patients, and establishes the first evidence of significant correlations between alpha power, FAA scores and measures of motor activity, which may be interpreted as an expression of impaired motivational drive in MDD. PMID- 26363267 TI - Elucidation of innovative antibiofilm materials. AB - It is known for roughly a decade that bacterial communities (called biofilms) are responsible for significant enhanced antibiotherapy resistance. Biofilms are involved in tissue persistent infection, causing direct or collateral damage leading to chronic wounds development and impairing natural wound healing. In this study, we are interested in the development of supported protein materials which consist of asymmetric membranes as reservoir supports for the incorporation and controlled release of biomolecules capable of dissolving biofilms (or preventing their formation) and their use as wound dressing for chronic wound treatment. In a first step, polyhydroxyalkanoates (PHAs) asymmetric membranes were prepared using wet phase inversion technique. Scanning microscopy (SEM) analysis has showed the influence of different processing parameters. In a second step, the porous side of the membranes were functionalized with a surface treatment and then loaded with the antibiofilm agent (dispersin B). In a third step, the properties and antibiofilm performance of the loaded-membranes were evaluated. Exposure of Staphylococcus epidermidis biofilms to such systems weakly inhibited biofilm formation (weak preventive effect) but caused their detachment and disaggregation (strong curative effect). These initial results are promising since they open the way to a new generation of effective tools in the struggle against persistent bacterial infections exhibiting enhanced antibiotherapy resistance, and in particular in the case of infected chronic wounds. PMID- 26363268 TI - Preparation, characterization, cellular response and in vivo osseointegration of polyetheretherketone/nano-hydroxyapatite/carbon fiber ternary biocomposite. AB - As FDA-approved implantable material, polyetheretherketone (PEEK) is becoming a prime candidate to replace traditional surgical metallic implants made of titanium (Ti) and its alloys, since it has a lower elastic modulus than Ti. The bioinertness and defective osteointegration of PEEK, however, limit its clinical adoption as load-bearing dental/orthopedic material. The present work aimed at developing a PEEK bioactive ternary composite, polyetheretherketone/nano hydroxyapatite/carbon fiber (PEEK/n-HA/CF), and evaluating it as a potential bone repairing material by assessment of growth and differentiation of osteoblast-like MG63 cells and by estimation of osteointegration in vivo. Our results indicated that the adhesion, proliferation and osteogenic differentiation of cells, as well as the mechanical properties were greatly promoted for the PEEK/n-HA/CF biocomposite compared with pure PEEK matrix. More importantly, the ternary composite implant boosted in vivo bioactivity and osseointegration in canine tooth defect model. Thus, the PEEK/n-HA/CF ternary biocomposite with enhanced mechanics and biological performances hold great potential as bioactive implant material in dental and orthopedic applications. PMID- 26363269 TI - Surface modification of zirconia with polydopamine to enhance fibroblast response and decrease bacterial activity in vitro: A potential technique for soft tissue engineering applications. AB - The quality of soft-tissue integration plays an important role in the short- and long-term success of dental implants. The aim of the present study was to provide a surface modification approach for zirconia implant abutment materials and to evaluate its influence on fibroblast behavior and oral bacteria adhesion, which are the two main factors influencing the quality of peri-implant soft-tissue seal. In this study, polydopamine (PDA)-coated zirconia was prepared and the surface characteristics were evaluated using scanning electron microscopy, atomic force microscopy, a contact-angle-measuring device, X-ray photoelectron spectroscopy, and Raman spectroscopy. The responses of human gingival fibroblasts (HGFs) to PDA-coated zirconia; i.e., adhesion, proliferation, morphology, protein synthesis, and gene expression, were analyzed. Additionally, the adhesion of Streptococcus gordonii and Streptococcus mutans to zirconia after PDA coating was assessed by scanning electron microscopy and live/dead staining. The material surface analyses suggested the successful coating of PDA onto the zirconia surface. The PDA coating significantly increased cell adhesion and proliferation compared with pristine zirconia. HGFs exhibited a high degree of spreading and secreted a high level of collagen type I on PDA-modified disks. Upregulation of integrin alpha5, beta1, beta3 and fibronectin was noted in HGFs cultured on PDA coated zirconia. The number of adherent bacteria decreased significantly on zirconia after PDA coating. In summary, our result suggest that PDA is able to modify the surface of zirconia, influence HGFs' behavior and reduce bacterial adhesion. Therefore, this surface modification approach holds great potential for improving soft-tissue integration around zirconia abutments in clinical application. PMID- 26363270 TI - Composite hydrogel of chitosan-poly(hydroxybutyrate-co-valerate) with chondroitin sulfate nanoparticles for nucleus pulposus tissue engineering. AB - Intervertebral disc degeneration, occurring mainly in nucleus pulposus (NP), is a leading cause of low back pain. In seeking to mitigate this condition, investigators in the field of NP tissue engineering have increasingly studied the use of hydrogels. However, these hydrogels should possess appropriate mechanical strength and swelling pressure, and concurrently support the proliferation of chondrocyte-like cells. The objective of this study was to develop and validate a composite hydrogel for NP tissue engineering, made of chitosan poly(hydroxybutyrate-co-valerate) (CP) with chondroitin sulfate (CS) nanoparticles, without using a cross linker. The water uptake ability, as well as the viscoelastic properties of this composite hydrogel, was similar to native tissue, as reflected in the complex shear modulus and stress relaxation values. The hydrogel could withstand varying stress corresponding to daily activities like lying down (0.01 MPa), sitting (0.5 MPa) and standing (1.0 MPa) under dynamic conditions. The hydrogels were stable in PBS for 2 weeks and its stiffness, elastic and viscous modulus did not alter significantly during this period. Both CP and CP-CS hydrogels could assist the viability and adhesion of adipose derived rat mesenchymal stem cells (ADMSCs). The viability and chondrogenic differentiation of MSCs was significantly enhanced in presence of CS nanoparticles. Thus, CS nanoparticles-incorporated chitosan-PHBV hydrogels offer great potential for NP tissue engineering. PMID- 26363271 TI - Frequent Gain and Loss of Resistance against Tobacco Mosaic Virus in Nicotiana Species. PMID- 26363272 TI - BZR1 Interacts with HY5 to Mediate Brassinosteroid- and Light-Regulated Cotyledon Opening in Arabidopsis in Darkness. AB - Light and brassinosteroid (BR) are two central stimuli that regulate plant photomorphogenesis. Although previous phenotypic and physiological studies have implied possible interactions between BR and light in regulating photomorphogenesis, the underlying molecular mechanism(s) remain largely unknown. In the present study, we identified a physical connection between the BR and light signaling pathways, which was mediated by the BR-regulated transcription factor BZR1 and light-regulated transcription factor HY5 in Arabidopsis thaliana. Genetic evidence showed that the gain-of-function bzr1-1D mutant in the BR signaling pathway and loss-of-function hy5-215 mutant in the light signaling pathway exhibited closed cotyledons under BR-deficient and dark-grown conditions and both bzr1-1D and hy5-215 mutants were able to suppress the cotyledon opening phenotype of the BR-insensitive mutants bri1-5 and bin2-1. Biochemical studies demonstrated that BZR1 interacts with HY5 both in vitro and in vivo and ectopic expression of HY5 considerably reduces the accumulation of BZR1 protein. In addition, HY5 specifically interacts with the dephosphorylated form of BZR1 and attenuates BZR1's transcriptional activity in regulating its target genes related to cotyledon opening. Our study provides a molecular framework for coordination of BR and light signals in regulating cotyledon opening, an important process in photomorphogenesis in plants. PMID- 26363274 TI - Responses of the sea anemone, Exaiptasia pallida, to ocean acidification conditions and copper exposure. AB - Ocean acidification (OA) is a growing concern due to its deleterious effects on aquatic organisms. Additionally, the combined effects of OA and other local stressors like metal pollution are largely unknown. In this study, we examined physiological effects in the sea anemone, Exaiptasia pallida after exposure to the global stressor carbon dioxide (CO2), as well as the local stressor copper (Cu) over 7 days. Cu accumulated in the tissues of E. pallida in a concentration dependent manner. At some time points, sea anemones exposed to 1000 ppm CO2 had higher tissue Cu concentrations than those exposed to 400 ppm CO2 at the same Cu exposure concentrations. In general, the activities of all anti-oxidant enzymes measured (catalase, CAT; glutathione peroxidase, GPx, glutathione reductase, GR) increased with exposure to increasing Cu concentrations. Significant differences in GR, CAT and to some degree GPx activity, were observed due to increasing CO2 exposure in control treatments. Sea anemones exposed to Cu in combination with higher CO2 generally had higher anti-oxidant enzyme activities than those exposed to the same concentration of Cu and lower CO2. Activity of the enzyme, carbonic anhydrase (CA), involved in acid-base balance, was significantly decreased with increasing Cu exposure. At the two lowest Cu concentrations, the extent of CA inhibition was lessened with increasing CO2 concentration. These results provide insight into toxic mechanisms of both Cu and CO2 exposure to the sensitive cnidarian E. pallida and have implications for environmental exposure of multiple contaminants. PMID- 26363273 TI - Three dimensionality of gleno-humeral deformities in obstetrical brachial plexus palsy. AB - The primary objective of this study was to test the hypothesis that gleno-humeral deformity in children and adolescent with obstetrical brachial plexus palsy is three-dimensional (3D). The study also compared the metrological properties of typical two-dimensional gleno-humeral measures to the newly developed 3D measures. Thirteen individuals (age = 11.8 +/- 3.3 years) with obstetrical brachial plexus palsy participated in this IRB-approved study. 3D axial magnetic resonance images were acquired for both shoulders. Glenoid and humeral models were created in order to quantify 3D glenoid version, humeral head migration, and glenoid concavity. Two-dimensional (2D) measures were acquired as recommended in the literature. All measures were completed by two observers in this observer blind study. Compared to the non-involved side, the glenoid was more retroverted (7.91 degrees , p = 0.003) and inferiorly oriented (7.28 degrees , p = 0.009). The humeral head was migrated more posteriorly (5.54 mm, p = 0.007), inferiorly ( 3.96 mm, p = 0.013), and medially (-3.63 mm,p = 0.002). Eleven of the 13 glenoids were concave, based on the 3D glenoid models. The concurrent validity between three- and 2D measures were highly dependent of the parameter measured, the slice level used for the 2D analysis, and the presence/absence of pathology (0.63 < r < 0.91). The standard error of measurement for the 2D anterior-posterior version (>3 degrees ) was larger than that for the 3D measure of version (<1 degrees ) on the involved side. This study clearly demonstrated that the gleno-humeral deformation in obstetrical brachial plexus palsy is 3D, emphasizing the need for 3D subject specific gleno-humeral shape analysis for follow-up and treatment plans in children with obstetrical brachial plexus palsy. PMID- 26363275 TI - Establishment of the first humpback whale fibroblast cell lines and their application in chemical risk assessment. AB - This paper reports the first successful derivation and characterization of humpback whale fibroblast cell lines. Primary fibroblasts were isolated from the dermal connective tissue of skin biopsies, cultured at 37 degrees C and 5% CO2 in the standard mammalian medium DMEM/F12 supplemented with 10% fetal bovine serum (FBS). Of nine initial biopsies, two cell lines were established from two different animals and designated HuWa1 and HuWa2. The cells have a stable karyotype with 2n=44, which has commonly been observed in other baleen whale species. Cells were verified as being fibroblasts based on their spindle-shaped morphology, adherence to plastic and positive immunoreaction to vimentin. Population doubling time was determined to be ~41 h and cells were successfully cryopreserved and thawed. To date, HuWa1 cells have been propagated 30 times. Cells proliferate at the tested temperatures, 30, 33.5 and 37 degrees C, but show the highest rate of proliferation at 37 degrees C. Short-term exposure to para,para'-dichlorodiphenyldichloroethylene (p,p'-DDE), a priority compound accumulating in southern hemisphere humpback whales, resulted in a concentration dependent loss of cell viability. The effective concentration which caused a 50% reduction in HuWa1 cell viability (EC50 value) was approximately six times greater than the EC50 value for the same chemical measured with human dermal fibroblasts. HuWa1 exposed to a natural, p,p'-DDE-containing, chemical mixture extracted from whale blubber showed distinctively higher sensitivity than to p,p' DDE alone. Thus, we provide the first cytotoxicological data for humpback whales and with establishment of the HuWa cell lines, a unique in vitro model for the study of the whales' sensitivity and cellular response to chemicals and other environmental stressors. PMID- 26363276 TI - Development of a Specific Latex Agglutination Test to Detect Antibodies of Enterovirus 71. AB - A latex agglutination test (LAT) was developed for the rapid detection of antibodies against the VP1 or VP1 proteins of Enterovirus 71 (EV71). The proteins of interest including prokaryotically expressed VP1 and two strains of anti-VP1 monoclonal antibody (McAb) against EV71 were covalently linked to carboxylated latex using ethyl-dimethyl-amino-propyl carbodiimide (EDC) to prepare sensitized latex beads. LAT was evaluated by an enzyme-linked immunosorbent assay (ELISA) as a reference test. The VP1-LAT showed a sensitivity of 87.0%, specificity of 88.9%, and an agreement ratio of 90.0% in detecting VP1 in 100 serum samples from experimentally infected mice, whereas these values were 86.8, 96.7, and 93.3%, respectively, for 608 clinical human serum samples. The VP1-LAT has advantages over other assays in terms of low cost, rapidity, chemical stability, high sensitivity, repeatability, and specificity. The LAT established in the present study is a rapid and simple test suitable for field monitoring of antibodies against VP1-EV71. PMID- 26363277 TI - The larval head anatomy of Rhyacophila (Rhyacophilidae) with discussion on mouthpart homology and the groundplan of Trichoptera. AB - The external and internal features of the larval head of Rhyacophila fasciata (Trichoptera: Rhyacophilidae) were described in detail. Anatomical examinations were carried out using a multimethod approach including histology, scanning electron microscopy, confocal laser-scanning microscopy, microcomputed tomography, and computer-based three-dimensional reconstructions. Additionally, the information on the larval head of Limnephilus flavicornis (Limnephilidae) and Hydropsyche angustipennis (Hydropsychidae) available in the literature were reinvestigated. These anatomical data were used to address major questions of homology and terminology, that is, the ventral closure of the head capsule, the sclerites, and appendages of labium and maxilla and their muscles. These topics were discussed by summarizing the main hypotheses present in the literature and a critical inclusion of new findings. Consequently, the inner lobe of the maxilla very likely represents the galea. The distal maxillary sclerite (palpifer) is an anatomical composite formation at least including dististipes and lacinia. Based on these homology hypotheses several potential groundplan features of the larval head of Trichoptera were reconstructed. The head of Rhyacophila shows several presumably plesiomorphic features as for instance the prognath orientation of the mouthparts, the well-developed hypocranial bridge, the triangular submentum and eyes composed of seven stemmata. Derived features of Rhyacophila are the reduced antennae, the anterior directing of three stemmata and the shift of the tentorio stipital muscle to the mentum. PMID- 26363278 TI - Therapeutic approaches of uncomplicated arterial hypertension in patients with COPD. AB - The concomitant presence of systemic arterial hypertension and chronic obstructive pulmonary disease (COPD) is frequent. Indeed, arterial hypertension is the most common comorbid disease in COPD patients. Since many antihypertensive drugs can act on airway function the treatment of arterial hypertension in COPD patients appears complex. Moreover, in these patients, a combined therapy is required for the adequate control of blood pressure. Currently, available data are inconsistent and not always comparable. Therefore the aim of this review is to analyze how antihypertensive drugs can affect airway function in order to improve the clinical management of hypertensive patients with COPD. Thiazide diuretics and calcium channel blockers appear the first-choice pharmacological treatment for these patients. PMID- 26363279 TI - Clarithromycin ameliorates pulmonary inflammation induced by short term cigarette smoke exposure in mice. AB - BACKGROUND: Cigarette smoking is considered to be one of major causes of acute worsening of asthma as well as chronic obstructive pulmonary disease (COPD). Macrolide antibiotics have been reported to reduce the risk of exacerbations of COPD, and possibly neutrophilic asthma. However, the effect of clarithromycin (CAM) on pulmonary inflammation caused by short term exposure to cigarette smoke still remains to be investigated. METHODS: C57BL/6J female mice were daily exposed to tobacco smoke using a tobacco smoke exposure system, or clean air for 8 days, while simultaneously treated with either oral CAM or vehicles. Twenty four hours after the last exposure, mice were anaesthetized and sacrificed, and bronchoalveolar lavage (BAL) fluids were collected. Cellular responses in BAL fluids were evaluated. Levels of cytokine mRNA in the lung tissues were measured by quantitative RT-PCR. Paraffin-embedded lung tissues were evaluated to quantitate degree of neutrophil infiltration. RESULTS: The numbers of total cells, macrophages and neutrophils in the BAL fluid of smoke-exposed mice were significantly increased as compared to clean air group. These changes were significantly ameliorated in CAM-treated mice. The lung morphological analysis confirmed decrease of neutrophils by CAM treatment. Studies by quantitative PCR demonstrated CAM treatment significantly reduced lung expression levels of IL 17A, keratinocyte-derived chemokine (KC), granulocyte-macrophage colony stimulating factor (GM-CSF) and MMP-9 induced by cigarette smoke. CONCLUSION: We demonstrate that CAM administration resolves enhanced pulmonary inflammation induced by short term cigarette smoke exposure in mice. PMID- 26363280 TI - Two new triterpenoid estersaponins and biological activities of Pittosporum tobira 'Variegata' (Thunb.) W. T. Aiton leaves. AB - Two new triterpenoid estersaponins (1, 2) were isolated from the leaves of Pittosporum tobira 'Variegata' (Thunb.) W. T. Aiton, along with one known saponin (3) and one known flavonoid glycoside (4). Their structures were established by different spectroscopic methods including 1D and 2D NMR, UV, as well as ESI-MS analysis. The investigated 80% aqueous methanol extract showed significant dose dependent inhibition of acetic acid induced abdominal writhing in mice. The n butanol fraction exerted moderate antimicrobial activity against Staphylococcus aureus and Escherichia coli. In addition, it showed in vitro antioxidant activity with IC50 value (7.3 MUg/ml) lower than that of the positive control ascorbic acid (11.2 MUg/ml), using DPPH free radical scavenging activity method. Evaluation of its in vitro cytotoxicity showed strong activity against breast carcinoma (MCF-7), hepatocellular carcinoma (HepG2), and colon carcinoma (HCT) cell lines. PMID- 26363281 TI - Practical considerations to drug dosing in children with acute kidney injury. AB - Medication dosing for children with acute kidney injury (AKI) needs to be individualized based on pharmacokinetic and pharmacodynamic principles of the prescribed drugswhenever possible to optimize therapeutic outcome and to minimize toxicity. The pediatric RIFLE criteria should be prospectively utilized to identify patients at highest risk of developing AKI. Serum creatinine and urine output along with volume status should be utilized to guide drug dosing when urinary biomarkers including kidney injury molecule 1, interleukin-18, or neutrophil gelatinase-associated lipocalin are not readily available. Because of the presence of a positive fluid balance in early stages of AKI, the dosing regimen for many drugs, especially antimicrobial agents, should be initiated at a larger loading dose based on the expected volume of distribution to achieve target serum concentrations.When possible, therapeutic drug monitoring should be utilized for those medications where serum drug concentrations can be obtained in a clinically relevant time frame. For these medications, close monitoring of serum drug concentrations is highly recommended. This review addresses drug dosing strategies in pediatric patients with AKI including the roles of therapeutic drug monitoring and newer kidney injury biomarkers. PMID- 26363282 TI - Characterization of beta-defensin 42 expressed in principal cells at the initial segment of the rat epididymis. AB - beta-defensins, preferentially expressed in male reproductive tracts, particularly in the testes and epididymis with region-specific patterns, play an important role in both innate immunity and sperm fertility. Expressed in the caput region of epididymis, beta-defensins have been known to contribute to innate immunity, sperm motility initiation, and maintenance. However, beta defensins of the initial region remain to be uncharacterized. In this study, rat beta-defensin 42 (Defb42) was revealed to be exclusively located in the principal cells at the initial segment of the rat epididymis and its sperm's acrosome. Furthermore, the expression of Defb42 was dependent on luminal testicular factors and developmental phases. The recombinant Defb42 was predominantly antimicrobial not against Candida albicans, but against Escherichia coli and Staphylococcus aureus. Based on these findings, Defb42 was suggested to play a dual role in sperm fertility and host defense in rat epididymis. PMID- 26363283 TI - The Role of Vascular Imaging in Guiding Routine Percutaneous Coronary Interventions: A Meta-Analysis of Bare Metal Stent and Drug-Eluting Stent Trials. AB - BACKGROUND: The routine use of vascular imaging including intravascular ultrasound (IVUS) and optical coherence tomography (OCT) in guiding percutaneous coronary interventions (PCI) is still controversial especially when using drug eluting stents. A meta-analysis of trials using bare metal stents was previously published. METHODS: We conducted a meta-analysis of available published trials that compared imaging-guided PCI and angiography-guided PCI in patients undergoing routine PCI only. Trials that enrolled patients with acute coronary syndrome were excluded to decrease heterogeneity. We aimed to study both drug eluting stents (DES) as well as bare metal stents (BMS). We identified seven randomized controlled trials on IVUS-guided bare metal stents. We also identified three randomized controlled trials on IVUS-guided drug-eluting stents. To improve the power of the drug-eluting stent data, we identified, and included, nine registries that compared IVUS-guided PCI to angiography-guided PCI in the drug eluting stent era. Nonrandomized registries that included BMS only were excluded as there are multiple previous meta-analyses that studied these patients. Finally, we identified one registry that compared OCT-guided PCI to angiography guided PCI using either a BMS or a DES. A total of 14,197 patients were studied overall. The meta-analysis was conducted using a random effect model. RESULTS: Imaging guidance was associated with a significantly larger postintervention minimal luminal diameter (SMD: 0.289. 95% CI: 0.213-0.365. P < 0.01). Imaging guided stenting was associated with a significant decrease in the major adverse cardiac events (MACE) in the DES patients (odds ratio: 0.810. 95% CI: 0.719 0.912. P < 0.01) and combined DES and BMS patients (odds ratio: 0.782. 95% CI: 0.686-0.890. P < 0.01). Imaging guidance was associated with significantly lower events of death from all causes in DES patients (odds ratio: 0.654. 95% CI: 0.468 0.916. P < 0.01) and in the combined DES and BMS patients (odds ratio: 0.727. 95% CI: 0.540-0.980. P < 0.01). The risk of myocardial infarction (MI) was significantly lower with imaging guidance in both, DES patients (odds ratio: 0.551. 95% CI: 0.363-0.837. P < 0.01) and combined DES and BMS patients (odds ratio: 0.589. 95% CI: 0.425-0.816. P < 0.01). This may, in part, be explained by the significantly lower risk of stent thrombosis in imaging-guided DES patients (odds ratio: 0.651. 95% CI: 0.499-0.850. P < 0.01) and combined DES and BMS patients (odds ratio: 0.665. 95% CI: 0.513-0.862. P < 0.01). Patients who received a DES showed no difference between imaging guidance and angiography guidance in repeated target lesion revascularization, while the analysis of BMS alone and the DES and BMS combined showed significant superiority of the imaging guided PCI group. CONCLUSION: Imaging-guided PCI significantly lowered the risk of death, MI, stent thrombosis, and the combined MACE in DES-implanted patients and all stented patients (DES or BMS). However, imaging guidance had no significant effect on repeated target vessel or target lesion revascularization in patients who received DES, likely due to the effect of the drug in the stent. PMID- 26363284 TI - Soil organic matter quantity and quality shape microbial community compositions of subtropical broadleaved forests. AB - As two major forest types in the subtropics, broadleaved evergreen and broadleaved deciduous forests have long interested ecologists. However, little is known about their belowground ecosystems despite their ecological importance in driving biogeochemical cycling. Here, we used Illumina MiSeq sequencing targeting 16S rRNA gene and a microarray named GeoChip targeting functional genes to analyse microbial communities in broadleaved evergreen and deciduous forest soils of Shennongjia Mountain of Central China, a region known as 'The Oriental Botanic Garden' for its extraordinarily rich biodiversity. We observed higher plant diversity and relatively richer nutrients in the broadleaved evergreen forest than the deciduous forest. In odds to our expectation that plant communities shaped soil microbial communities, we found that soil organic matter quantity and quality, but not plant community parameters, were the best predictors of microbial communities. Actinobacteria, a copiotrophic phylum, was more abundant in the broadleaved evergreen forest, while Verrucomicrobia, an oligotrophic phylum, was more abundant in the broadleaved deciduous forest. The density of the correlation network of microbial OTUs was higher in the broadleaved deciduous forest but its modularity was smaller, reflecting lower resistance to environment changes. In addition, keystone OTUs of the broadleaved deciduous forest were mainly oligotrophic. Microbial functional genes associated with recalcitrant carbon degradation were also more abundant in the broadleaved deciduous forests, resulting in low accumulation of organic matters. Collectively, these findings revealed the important role of soil organic matter in shaping microbial taxonomic and functional traits. PMID- 26363285 TI - Comparison of Psychophysiological and Dual-Task Measures of Listening Effort. AB - PURPOSE: We wished to make a comparison of psychophysiological measures of listening effort with subjective and dual-task measures of listening effort for a diotic-dichotic-digits and a sentences-in-noise task. METHOD: Three groups of young adults (18-38 years old) with normal hearing participated in three experiments: two psychophysiological studies for two different listening tasks and a dual-task measure for a sentences-in-noise task. Psychophysiological variables included skin conductance, heart-rate variability, and heart rate; the dual-task measure was a letter-identification task. Heart-rate variability was quantified with the difference from baseline for the normalized standard deviation of R to R. RESULTS: Heart-rate variability differences from baseline were greater for increased task complexity and for poorer signal-to-noise ratios (SNRs). The dual-task measure of listening effort also increased for sentences presented at a +5 dB SNR compared with a +15 dB SNR. Skin conductance was elevated for greater task complexity only, and similar across noise conditions. None of these measures were significantly correlated with subjective measures of listening effort. CONCLUSIONS: Heart-rate variability appears to be a robust psychophysiological indicator of listening effort, sensitive to both task complexity and SNR. This sensitivity to SNR was similar to a dual-task measure of listening effort. PMID- 26363287 TI - Antenatal cardiotocography for fetal assessment. AB - BACKGROUND: Cardiotocography (CTG) is a continuous recording of the fetal heart rate obtained via an ultrasound transducer placed on the mother's abdomen. CTG is widely used in pregnancy as a method of assessing fetal well-being, predominantly in pregnancies with increased risk of complications. OBJECTIVES: To assess the effectiveness of antenatal CTG (both traditional and computerised assessments) in improving outcomes for mothers and babies during and after pregnancy. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (26 June 2015) and reference lists of retrieved studies. SELECTION CRITERIA: Randomised and quasi-randomised trials that compared traditional antenatal CTG with no CTG or CTG results concealed; computerised CTG with no CTG or CTG results concealed; and computerised CTG with traditional CTG. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. MAIN RESULTS: Six studies (involving 2105 women) are included. Overall, the included studies were not of high quality, and only two had both adequate randomisation sequence generation and allocation concealment. All studies that were able to be included enrolled only women at increased risk of complications.Comparison of traditional CTG versus no CTG showed no significant difference identified in perinatal mortality (risk ratio (RR) 2.05, 95% confidence interval (CI) 0.95 to 4.42, 2.3% versus 1.1%, four studies, N = 1627, low quality evidence) or potentially preventable deaths (RR 2.46, 95% CI 0.96 to 6.30, four studies, N = 1627), though the meta-analysis was underpowered to assess this outcome. Similarly, there was no significant difference identified in caesarean sections (RR 1.06, 95% CI 0.88 to 1.28, 19.7% versus 18.5%, three trials, N = 1279, low quality evidence). There was also no significant difference identified for secondary outcomes related to Apgar scores less than seven at five minutes (RR 0.83, 95% CI 0.37 to 1.88, one trial, N = 396, very low quality evidence); or admission to neonatal special care units or neonatal intensive care units (RR 1.08, 95% CI 0.84 to 1.39, two trials, N = 883, low quality evidence), nor in the other secondary outcomes that were assessed.There were no eligible studies that compared computerised CTG with no CTG.Comparison of computerised CTG versus traditional CTG showed a significant reduction in perinatal mortality with computerised CTG (RR 0.20, 95% CI 0.04 to 0.88, two studies, 0.9% versus 4.2%, 469 women, moderate quality evidence). However, there was no significant difference identified in potentially preventable deaths (RR 0.23, 95% CI 0.04 to 1.29, two studies, N = 469), though the meta-analysis was underpowered to assess this outcome. There was no significant difference identified in caesarean sections (RR 0.87, 95% CI 0.61 to 1.24, 63% versus 72%, one study, N = 59, low quality evidence), Apgar scores less than seven at five minutes (RR 1.31, 95% CI 0.30 to 5.74, two studies, N = 469, very low quality evidence) or in secondary outcomes. AUTHORS' CONCLUSIONS: There is no clear evidence that antenatal CTG improves perinatal outcome, but further studies focusing on the use of computerised CTG in specific populations of women with increased risk of complications are warranted. PMID- 26363286 TI - CCN1 Regulates Chondrocyte Maturation and Cartilage Development. AB - WNT/beta-CATENIN signaling is involved in multiple aspects of skeletal development, including chondrocyte differentiation and maturation. Although the functions of beta-CATENIN in chondrocytes have been extensively investigated through gain-of-function and loss-of-function mouse models, the precise downstream effectors through which beta-CATENIN regulates these processes are not well defined. Here, we report that the matricellular protein, CCN1, is induced by WNT/beta-CATENIN signaling in chondrocytes. Specifically, we found that beta CATENIN signaling promotes CCN1 expression in isolated primary sternal chondrocytes and both embryonic and postnatal cartilage. Additionally, we show that, in vitro, CCN1 overexpression promotes chondrocyte maturation, whereas inhibition of endogenous CCN1 function inhibits maturation. To explore the role of CCN1 on cartilage development and homeostasis in vivo, we generated a novel transgenic mouse model for conditional Ccn1 overexpression and show that cartilage-specific CCN1 overexpression leads to chondrodysplasia during development and cartilage degeneration in adult mice. Finally, we demonstrate that CCN1 expression increases in mouse knee joint tissues after meniscal/ligamentous injury (MLI) and in human cartilage after meniscal tear. Collectively, our data suggest that CCN1 is an important regulator of chondrocyte maturation during cartilage development and homeostasis. PMID- 26363288 TI - The long journey of botulinum neurotoxins into the synapse. AB - Botulinum neurotoxins (BoNT) cause the disease botulism, a flaccid paralysis of the muscle. They are also very effective, widely used medicines applied locally in sub-nanogram quantities. BoNTs are released together with several non-toxic, associated proteins as progenitor toxin complexes (PCT) by Clostridium botulinum to become highly potent oral poisons ingested via contaminated food. They block the neurotransmission in susceptible animals and humans already in nanogram quantities due to their specific ability to enter motoneurons and to cleave only selected neuronal proteins involved in neuroexocytosis. BoNTs have developed a sophisticated strategy to passage the gastrointestinal tract and to be absorbed in the intestine of the host to finally attack neurons. A non-toxic non hemagglutinin (NTNHA) forms a binary complex with BoNT to protect it from gastrointestinal degradation. This binary M-PTC is one component of the bi modular 14-subunit ~760 kDa large progenitor toxin complex. The other component is the structurally and functionally independent dodecameric hemagglutinin (HA) complex which facilitates the absorption on the intestinal epithelium by glycan binding. Subsequent to its transcytosis the HA complex disrupts the tight junction of the intestinal barrier from the basolateral side by binding to E cadherin. Now, the L-PTC can also enter the circulation by paracellular routes in much larger quantities. From here, the dissociated BoNTs reach the neuromuscular junction and accumulate via interaction with polysialo gangliosides, complex glycolipids, on motoneurons at the neuromuscular junction. Subsequently, additional specific binding to luminal segments of synaptic vesicles proteins like SV2 and synaptotagmin leads to their uptake. Finally, the neurotoxins shut down the synaptic vesicle cycle, which they had exploited before to enter their target cells, via specific cleavage of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins, which constitute the core components of the cellular membrane fusion machinery. PMID- 26363289 TI - BbMP-1, a new metalloproteinase isolated from Bothrops brazili snake venom with in vitro antiplasmodial properties. AB - This study describes the biochemical and functional characterization of a new metalloproteinase named BbMP-1, isolated from Bothrops brazili venom. BbMP-1 was homogeneous on SDS-PAGE, presented molecular mass of 22,933Da and pI 6.4. The primary structure was partially elucidated with high identity with others metalloproteinases from Viperidae venoms. The enzymatic activity on azocasein was evaluated in different experimental conditions (pH, temperature). A significant reduction in enzyme activity after exposure to chelators of divalent cations (EDTA), reducing agents (DTT), pH less than 5.0 or temperatures higher than 45 degrees C was observed. BbMP-1 showed activity on fibrinogen degrading Aalpha chain quickly and to a lesser extent the Bbeta chain. Also demostrated to be weakly hemorrhagic, presenting however, significant myotoxic and edematogenic activity. The in vitro activity of BbMP-1 against Plasmodium falciparum showed an IC50 of 3.2 +/- 2.0 MUg/mL. This study may help to understand the pathophysiological effects induced by this group of toxin and their participation in the symptoms observed in cases of snake envenomation. Moreover, this result is representative for this group of proteins and shows the biotechnological potential of BbMP-1 by the demonstration of its antiplasmodial activity. PMID- 26363290 TI - A new Kunitz-type plasmin inhibitor from scorpion venom. AB - Kunitz-type peptides from venomous animals are an important source of lead drug candidates towards human plasmin, a target of protease-associated diseases. However, no Kunitz-type plasmin inhibitor from venomous scorpion has been characterized. Here, we first investigated plasmin inhibiting activities of eight known Kunitz-type scorpion toxins Hg1, BmKTT-1, BmKTT-2, BmKTT-3, LmKTT-1a, LmKTT 1b, LmKTT-1c and BmKPI, and found a new plasmin inhibitor BmKTT-2, a Kunitz-type toxin peptide from the scorpion Buthus martensi karch. Protease inhibitory activity assay showed that BmKTT-2 potently inhibited plasmin with a Ki value of 8.75 +/- 2.05 nM. Structure-function relationship studies between BmKTT-2 and plasmin showed that BmKTT-2 is a classical Kunitz-type plasmin inhibitor: Lys13 in BmKTT-2 is the P1 site, and Ala14 in BmKTT-2 is the P1' site. Interestingly, BmKTT-2 has potent inhibiting activities towards three important digestive serine proteases trypsin, chymotrypsin and elastase, suggesting a good stability for administering oral medications. To the best of our knowledge, BmKTT-2 is the first Kunitz-type human plasmin inhibitor from scorpion venom, providing novel insights into drug developments targeting human plasmin protease. PMID- 26363291 TI - Congenital malformations caused by Stryphnodendron fissuratum (Leg. Mimosoideae) in guinea pigs (Cavia porcellus). AB - The aim of this study was to evaluate the toxicity of Stryphnodendron fissuratum pods in guinea pigs (Cavia porcellus) and test the hypothesis that this plant has teratogenic effects. Thus, sixteen guinea pigs were randomly divided into four groups of four animals each. Groups 10, 20 and 40 consisted of guinea pigs that received commercial food that contained crushed pods of S. fissuratum at concentrations of 10, 20 and 40 g/kg, respectively, during the period of organogenesis. Control group consisted of guinea pigs under the same management conditions that did not receive crushed pods of S. fissuratum in their food. In all experimental groups, the main clinical signs of poisoning consisted of anorexia, prostration, absence of vocalizations, alopecia, diarrhea, and abortions within the adult guinea pigs. Those that did not abort gave birth to weak, malnourished pups, some of which had fetal malformations. The main teratogenic changes consisted of eventration, arthrogryposis, amelia of the forelimbs, anophthalmia, microphthalmia, anotia and agnathia. The reductions in the number of offspring and the malformations observed in the experimental groups suggest that S. fissuratum affects fetal development and is teratogenic. PMID- 26363292 TI - Transcripts involved in hemostasis: Exploring salivary complexes from Haementeria vizottoi leeches through transcriptomics, phylogenetic studies and structural features. AB - Throughout evolution, parasites have adapted in order to successfully intervene in the host defense, producing specific peptides and proteins. Interestingly, these peptides and proteins have been exploited as potential drug candidates against several diseases. Furthermore, biotechnology studies and cDNA libraries have remarkably contributed to identify potentially bioactive molecules. In this regard, herein, a cDNA library of salivary complexes from Haementeria vizottoi leeches was constructed, the transcriptome was characterized and a phylogenetic analysis was performed considering antistasin-like and antiplatelet-like proteins. Hundred twenty three transcripts were identified coding for putative proteins involved in animal feeding (representing about 10% of the expression level). These sequences showed similarities with myohemerythrins, carbonic anhydrases, anticoagulants, antimicrobials, proteases and protease inhibitors. The phylogenetic analysis, regarding antistasin-like and antiplatetlet-like proteins, revealed two main clades in the Rhynchobdellida leeches. As expected, the sequences from H. vizottoi have presented high similarities with those types of proteins. Thus, our findings could be helpful not only to identify new coagulation inhibitors, but also to better understand the biological composition of the salivary complexes. PMID- 26363293 TI - Functional importance of the Gly cluster in transmembrane helix 2 of the Bordetella pertussis CyaA-hemolysin: Implications for toxin oligomerization and pore formation. AB - Adenylate cyclase-hemolysin (CyaA) is a major virulence factor of Bordetella pertussis causing whooping cough in humans. We previously showed that two transmembrane helices (alpha2 and alpha3) in the hemolysin domain (CyaA-Hly) are crucially involved in hemolytic activity. Here, PCR-based substitutions were employed to investigate a potential involvement in hemolysis of a series of four Gly residues (Gly(530), Gly(533), Gly(537) and Gly(544)) which map onto one face of a helical wheel plot of pore-lining helix 2. All CyaA-Hly mutant toxins were over-expressed in Escherichia coli as 126-kDa soluble proteins at levels comparable to the wild-type toxin. A drastic reduction in hemolytic activity against sheep erythrocytes was observed for three CyaA-Hly mutants, i.e. G530A, G533A and G537A, but not G544A, suggesting a functional importance of the Gly(530)_Gly(533)_Gly(537) cluster. A homology-based structure of the alpha2-loop alpha3 hairpin revealed that this crucial Gly cluster arranged as a GXXGXXXG motif is conceivably involved in helix-helix association. Furthermore, a plausible pore model comprising three alpha2-loop-alpha3 hairpins implicated that Gly(530)XXGly(533)XXXGly(537) could function as an important framework for toxin oligomerization. Altogether, our present data signify for the first time that the Gly(530)_Gly(533)_Gly(537) cluster in transmembrane helix 2 serves as a crucial constituent of the CyaA-Hly trimeric pore structure. PMID- 26363294 TI - Functional characterization of the Tetranychus urticae CYP392A11, a cytochrome P450 that hydroxylates the METI acaricides cyenopyrafen and fenpyroximate. AB - Cyenopyrafen is a Mitochondrial Electron Transport Inhibitor (METI) acaricide with a novel mode of action at complex II, which has been recently developed for the control of the spider mite Tetranychus urticae, a pest of eminent importance globally. However, some populations of T. urticae are cross-resistant to this molecule, and cyenopyrafen resistance can be readily selected in the lab. The cytochrome P450s genes CYP392A11 and CYP392A12 have been strongly associated with the phenotype. We expressed the CYP392A11 and the CYP392A12 genes with T. urticae cytochrome P450 reductase (CPR) in Escherichia coli. CYP392A12 was expressed predominately as an inactive form, witnessed by a peak at P420, despite optimization efforts on expression conditions. However, expression of CYP392A11 produced a functional enzyme, with high activity and preference for the substrates Luciferin-ME EGE and ethoxycoumarin. CYP392A11 catalyses the conversion of cyenopyrafen to a hydroxylated analogue (kcat = 2.37 pmol/min/pmol P450), as well as the hydroxylation of fenpyroximate (kcat = 1.85 pmol/min/pmol P450). In addition, transgenic expression of CYP392A11 in Drosophila melanogaster, in conjunction with TuCPR, confers significant levels of fenpyroximate resistance. The overexpression of CYP392A11 in multi-resistant T. urticae strains, not previously exposed to cyenopyrafen, which had been indicated by microarray studies, was confirmed by qPCR, and it was correlated with significant levels of cyenopyrafen and fenpyroximate cross-resistance. The implications of our findings for insecticide resistance management strategies are discussed. PMID- 26363295 TI - BmBR-C Z4 is an upstream regulatory factor of BmPOUM2 controlling the pupal specific expression of BmWCP4 in the silkworm, Bombyx mori. AB - 20-hydroxyecdysone (20E)-induced expression of the wing disc cuticle protein gene BmWCP4 was mediated by the transcription factor BmPOUM2, which binds to the cis response elements (CREs) of BmWCP4 gene in Bombyx mori. In this study we report the regulation of BmPOUM2. RT-PCR analysis indicated that in response to 20E, BmPOUM2 was expressed at higher levels in the wing discs during the pre-pupal and mid-pupal stages than other stages and the expression pattern of BmBR-C Z1, BmBR C Z2 and BmBR-C Z4 was in tandem with the expression of BmPOUM2. BmBR-C Z4 was induced by 20E in the wing discs, whereas BmBR-C Z1 and BmBR-C Z2 were not. Three potential BR-C Z4 cis-response elements (CREs) were identified in the promoter region of BmPOUM2. The expression of BmPOUM2 mRNA and protein was increased by the over-expression of BmBR-C Z4 in BmN cells, which acted at the promoter of BmPOUM2. Electrophoretic mobility shift assay (EMSA) and the luciferase activity analysis under the control of wild-type and mutants of the BR-C Z4 CREs suggested that BmBR-C Z4 protein bound to the predicted BRC-Z4 CRE C (-684 ~ -660). Taken together the data suggest that BmBR-C Z4 is a direct upstream regulator of BmPOUM2 and regulates the pupal-specific expression of BmWCP4 through BmPOUM2. PMID- 26363296 TI - Transposition burst of mariner-like elements in the sequenced genome of Rhodnius prolixus. AB - Transposable elements (TEs) are widespread in insect's genomes. However, there are wide differences in the proportion of the total DNA content occupied by these repetitive sequences in different species. We have analyzed the TEs present in R. prolixus (vector of the Chagas disease) and showed that 3.0% of this genome is occupied by Class II TEs, belonging mainly to the Tc1-mariner superfamily (1.65%) and MITEs (1.84%). Interestingly, most of this genomic content is due to the expansion of two subfamilies belonging to: irritans himar, a well characterized subfamily of mariners, and prolixus1, one of the two novel subfamilies here described. The high amount of sequences in these subfamilies suggests that bursts of transposition occurred during the life cycle of this family. In an attempt to characterize these elements, we performed an in silico analysis of the sequences corresponding to the DDD/E domain of the transposase gene. We performed an evolutionary analysis including network and Bayesian coalescent-based methods in order to infer the dynamics of the amplification, as well as to estimate the time of the bursts identified in these subfamilies. Given our data, we hypothesized that the TE expansions occurred around the time of speciation of R. prolixus around 1.4 mya. This suggestion lays on the "Transposon Model" of TE evolution, in which the members of a TE population that are replicative active are present at multiple loci in the genome, but their replicative potential varies, and of the "Life Cycle Model" that states that when present-day TEs have been involved in amplification bursts, they share an ancestral copy that dates back to this initial amplification. PMID- 26363297 TI - A point mutation in the acetylcholinesterase-1 gene is associated with chlorpyrifos resistance in the plant bug Apolygus lucorum. AB - Control of Chinese Apolygus lucorum relies heavily on organophosphate insecticides. Here we describe resistance to the organophosphate chlorpyrifos in an A. lucorum strain, BZ-R, which was developed from a field-collected strain (BZ) by selection with chlorpyrifos in the laboratory. BZ-R showed 21-58 fold resistance to chlorpyrifos compared with the laboratory reference strain LSF and another susceptible strain, BZ-S, derived from BZ. BZ-R also showed several fold resistance to two other organophosphates and a carbamate. No synergism of chlorpyrifos by metabolic enzyme inhibitors nor any increase in detoxifying enzyme activities were observed in BZ-R. No sequence differences in acetylcholinesterase-2 were found to be associated with the resistance but the frequency of an alanine to serine substitution at position 216 of acetylcholinesterase-1 was 100% in BZ-R, ~21-23% in SLF and BZ, and 0% in BZ-S. A single generation treatment of chlorpyrifos on the BZ strain also increased its frequency of the serine substitution to 64%. Recombinantly expressed acetylcholinesterase-1 carrying the serine substitution was about five fold less sensitive to inhibition by chlorpyrifos oxon than the wild-type enzyme. Quantitative real-time PCR found no differences in ace1 or ace2 expression levels among the strains tested. Thus the chlorpyrifos resistance is strongly associated with the serine substituted acetylcholinesterase-1. An equivalent substitution has been found to confer resistance to many organophosphate and carbamate insecticides in four other insect species. PMID- 26363298 TI - Longitudinal analysis of peripheral and intrahepatic NK cells in chronic HCV patients during antiviral therapy. AB - INTRODUCTION: A strong immune response is integral to the clearance of HCV infection. NK cells are specialized cells that are able to inhibit replication of HCV in infected hepatocytes. Previous studies have correlated therapy outcome in HCV to the expression of various markers on NK cells. However, the effect of viral load reduction on NK cell function during therapy is still largely unknown, particularly in the liver. Therefore we investigated NK cell phenotype and effector function in both the peripheral and intrahepatic compartments during the course of antiviral therapy in chronic HCV patients. METHODS: Chronic HCV patients were treated for 24 or 48weeks with triple therapy consisting of telaprevir, pegIFN-alpha and ribavirin. Blood and fine needle aspiration (FNA) biopsies of the liver were collected at start and 6h, 1week and 12weeks during therapy. Flowcytometry was performed for expression of different markers (NKG2A, NKG2D, NKp46, and CD69). RESULTS: Our results demonstrate a highly activated phenotype of NK cells in liver compared to blood in chronic HCV patients. Six hours after start of triple therapy, no activation of intrahepatic NK cells was observed in the liver as compared to baseline. At 1week after start of triple therapy, the frequency of NK cells with the activating receptor NKp46 was increased in blood, whereas at week 12, the frequencies of the inhibitory receptor NKG2A was increased. No alterations were observed during therapy in liver NK cell phenotype. CONCLUSION: IFN-based therapy for chronic HCV affects NK cell phenotype in peripheral blood more than in the liver. PMID- 26363299 TI - Right fronto-limbic atrophy is associated with reduced empathy in refractory unilateral mesial temporal lobe epilepsy. AB - Refractory mesial temporal lobe epilepsy (MTLE) is the most frequent focal epilepsy and is often accompanied by deficits in social cognition including emotion recognition, theory of mind, and empathy. Consistent with the neuronal networks that are crucial for normal social-cognitive processing, these impairments have been associated with functional changes in fronto-temporal regions. However, although atrophy in unilateral MTLE also affects regions of the temporal and frontal lobes that underlie social cognition, little is known about the structural correlates of social-cognitive deficits in refractory MTLE. In the present study, a psychometrically validated empathy questionnaire was combined with whole-brain voxel-based morphometry (VBM) to investigate the relationship between self-reported affective and cognitive empathy and gray matter volume in 55 subjects (13 patients with right MTLE, 9 patients with left MTLE, and 33 healthy controls). Consistent with the brain regions underlying social cognition, our results show that lower affective and cognitive empathy was associated with smaller volume in predominantly right fronto-limbic regions, including the right hippocampus, parahippocampal gyrus, thalamus, fusiform gyrus, inferior temporal gyrus, dorsomedial and dorsolateral prefrontal cortices, and in the bilateral midbrain. The only region that was associated with both affective and cognitive empathy was the right mesial temporal lobe. These findings indicate that patients with right MTLE are at increased risk for reduced empathy towards others' internal states and they shed new light on the structural correlates of impaired social cognition frequently accompanying refractory MTLE. In line with previous evidence from patients with neurodegenerative disease and stroke, the present study suggests that empathy depends upon the integrity of right fronto-limbic and brainstem regions and highlights the importance of the right mesial temporal lobe and midbrain structures for human empathy. PMID- 26363300 TI - Current strategies for sustaining drug release from electrospun nanofibers. AB - Electrospun drug-eluting fibers are emerging as a novel dosage form for multipurpose prevention against sexually transmitted infections, including HIV, and unintended pregnancy. Previous work from our lab and others show the versatility of this platform to deliver large doses of physico-chemically diverse agents. However, there is still an unmet need to develop practical fiber formulations for water-soluble small molecule drugs needed at high dosing due to intrinsic low potency or desire for sustained prevention. To date, most sustained release fibers have been restricted to the delivery of biologics or hydrophobic small molecules at low drug loading of typically <1 wt.%, which is often impractical for most clinical applications. For hydrophilic small molecule drugs, their high aqueous solubility and poor partitioning and incompatibility with insoluble polymers make long-term release even more challenging. Here we investigate several existing strategies to sustain release of hydrophilic small molecule drugs that are highly-loaded in electrospun fibers. In particular, we investigate what is known about the design constraints required to realize multi day release from fibers fabricated from uniaxial and coaxial electrospinning. PMID- 26363301 TI - Bio-inspired materials in drug delivery: Exploring the role of pulmonary surfactant in siRNA inhalation therapy. AB - Many pathologies of the respiratory tract are inadequately treated with existing small molecule-based therapies. The emergence of RNA interference (RNAi) enables the post-transcriptional silencing of key molecular disease factors that cannot readily be targeted with conventional small molecule drugs. Pulmonary administration of RNAi effectors, such as small interfering RNA (siRNA), allows direct delivery into the lung tissue, hence reducing systemic exposure. Unfortunately, the clinical translation of RNAi is severely hampered by inefficient delivery of siRNA therapeutics towards the cytoplasm of the target cells. In order to have a better control of the siRNA delivery process, both extra- and intracellular, siRNAs are typically formulated in nanosized delivery vehicles (nanoparticles, NPs). In the lower airways, which are the targeted sites of action for multiple pulmonary disorders, these siRNA-loaded NPs will encounter the pulmonary surfactant (PS) layer, covering the entire alveolar surface. The interaction between the instilled siRNA-loaded NPs and the PS at this nano-bio interface results in the adsorption of PS components onto the surface of the NPs. The formation of this so-called biomolecular corona conceals the original NP surface and will therefore profoundly determine the biological efficacy of the NP. Though this interplay has initially been regarded as a barrier towards efficient siRNA delivery to the respiratory target cell, recent reports have illustrated that the interaction with PS might also be beneficial for local pulmonary siRNA delivery. PMID- 26363303 TI - Phase separation in lipid bilayer membranes induced by intermixing at a boundary of two phases with different components. AB - We have demonstrated that dynamic phase separation is induced by coalescence of two self-spreading supported lipid bilayers (SLBs) with different components. Coalescence between a phosphocholine/sphingolipid SLB and a phosphocholine/cholesterol one forms raft-like liquid ordered (Lo) domains, which can be observed by fluorescence microscopy at the boundary of two phases. This phase separation process indicates that lipid molecules, such as sphingolipid and cholesterol, are intermixed. When saturated phospholipid is used instead of sphingolipid, small Lo domains are formed. Cholesterol is harder to incorporate with domains of saturated phospholipid than that of sphingolipid. This technique is very useful for observation of lipid-lipid interactions. PMID- 26363304 TI - Friends in low places: The impact of locations and companions on 21st birthday drinking. AB - The present research examined how various locations and companions were associated with hazardous drinking during 21st birthday celebrations. The sample included 912 college students (57% female) who completed an online survey to examine 21st birthday drinking. Locations included bars, friends' houses, restaurants, outdoor barbecues, homes, parents' homes, and Fraternity/Sorority houses. Companions included friends, family members, casual acquaintances, roommates, significant others, Fraternity/Sorority members, and none (alone). Participants consumed an average of 7.6 drinks and reached an average eBAC of .15 during their 21st birthday celebrations. Locations accounted for 20%/18% of the variance in number of drinks and eBAC, respectively, whereas companions accounted for 23%/20% of the variance. Drinking with romantic partners was associated with less drinking, whereas drinking with Fraternity/Sorority members was associated with more drinking. Stepwise regressions combining locations and companions suggested that, overall, celebrating in a bar setting and with Fraternity and Sorority members were the strongest variables associated with drinking. With the exception of a bar setting, companions were the most important contextual factors associated with 21st birthday drinking. PMID- 26363305 TI - Single-session interventions for problem gambling may be as effective as longer treatments: Results of a randomized control trial. AB - Empirically supported treatments for problem gambling tend to be multimodal combining cognitive, behavior and motivational interventions. Since problem gamblers often prefer briefer treatments it is important that interventions adopt strategies that are optimally effective. In this study, 99 community-recruited problem gamblers (74% male, mean age: 47.5 years) were randomized to one of four treatments: six sessions of cognitive therapy, behavior therapy, and motivational therapy or a single-session intervention. The sample was followed up for 12 months post-treatment. In both the Intent-to-Treat and Completer statistical analyses, no significant group differences on key gambling variables (i.e., frequency, expenditures, severity) were found. All four treatments showed significant improvement as a result of treatment that endured throughout the follow-up period. These results, although preliminary, suggest that very brief, single-session interventions may be as effective as longer treatments. PMID- 26363302 TI - DNA methylation changes in epithelial ovarian cancer histotypes. AB - Survival after a diagnosis of ovarian cancer has not improved, and despite histological differences, treatment is similar for all cases. Understanding the molecular basis for ovarian cancer risk and prognosis is fundamental, and to this end much has been gleaned about genetic changes contributing to risk, and to a lesser extent, survival. There's considerable evidence for genetic differences between the four pathologically defined histological subtypes; however, the contribution of epigenetics is less well documented. In this report, we review alterations in DNA methylation in ovarian cancer, focusing on histological subtypes, and studies examining the roles of methylation in determining therapy response. As epigenetics is making its way into clinical care, we review the application of cell free DNA methylation to ovarian cancer diagnosis and care. Finally, we comment on recurrent limitations in the DNA methylation literature for ovarian cancer, which can and should be addressed to mature this field. PMID- 26363306 TI - An experimental test of assessment reactivity within a web-based brief alcohol intervention study for college students. AB - OBJECTIVE: Web-based brief alcohol intervention (WBI) programs have efficacy in a wide range of college students and have been widely disseminated to universities to address heavy alcohol use. In the majority of efficacy studies, web-based research assessments were conducted before the intervention. Web-based research assessments may elicit reactivity, which could inflate estimates of WBI efficacy. The current study tested whether web-based research assessments conducted in combination with a WBI had additive effects on alcohol use outcomes, compared to a WBI only. METHODS: Undergraduate students (n=856) from universities in the United States and Canada participated in this online study. Eligible individuals were randomized to complete 1) research assessments+WBI or 2) WBI-only. Alcohol consumption, alcohol-related problems, and protective behaviors were assessed at one-month follow up. RESULTS: Multiple regression using 20 multiply imputed datasets indicated that there were no significant differences at follow up in alcohol use, alcohol-related problems, or protective behaviors used when controlling for variables with theoretical and statistical relevance. A repeated measures analysis of covariance revealed a significant decrease in peak estimated blood alcohol concentration in both groups, but no differential effects by randomized group. There were no significant moderating effects from gender, hazardous alcohol use, or motivation to change drinking. CONCLUSIONS: Web-based research assessments combined with a web-based alcohol intervention did not inflate estimates of intervention efficacy when measured within-subjects. Our findings suggest universities may be observing intervention effects similar to those cited in efficacy studies, although effectiveness trials are needed. PMID- 26363307 TI - Drinking norms, readiness to change, and gender as moderators of a combined alcohol intervention for first-year college students. AB - INTRODUCTION: Alcohol interventions targeting college students and their parents have been shown to be efficacious. Little research has examined moderators of intervention efficacy to help tailor interventions for subgroups of students. METHOD: This study is a secondary data analysis of readiness to change, drinking norms, and gender as moderators of an efficacious peer- and parent-based intervention (Turrisi et al., 2009). Students (n=680) were randomized to the combined peer and parent intervention (n=342) or assessment-only control (n=338). RESULTS: The combined intervention reduced peak blood alcohol content (BAC) compared to control. Gender and norms did not moderate the relationship between the intervention and drinking. Significant interactions were found between gender, precontemplation, and intervention. Students in the combined condition with higher precontemplation had lower weekly drinking compared to those with lower precontemplation. This pattern was also found among men for peak BAC and alcohol-related consequences but not among women, indicating a three-way interaction. CONCLUSION: Interventions may need to consider readiness to change and gender to optimize effectiveness. PMID- 26363308 TI - Toxicology of 3-epi-deoxynivalenol, a deoxynivalenol-transformation product by Devosia mutans 17-2-E-8. AB - Microbial detoxification of deoxynivalenol (DON) represents a new approach to treating DON-contaminated grains. A bacterium Devosia mutans 17-2-E-8 was capable of completely transforming DON into a major product 3-epi-DON and a minor product 3-keto-DON. Evaluation of toxicities of these DON-transformation products is an important part of hazard characterization prior to commercialization of the biotransformation application. Cytotoxicities of the products were demonstrated by two assays: a MTT bioassay assessing cell viability and a BrdU assay assessing DNA synthesis. Compared with DON, the IC50 values of 3-epi-DON and 3-keto-DON were respectively 357 and 3.03 times higher in the MTT bioassay, and were respectively 1181 and 4.54 times higher in the BrdU bioassay. Toxicological effects of 14-day oral exposure of the B6C3F1 mouse to DON and 3-epi-DON were also investigated. Overall, there were no differences between the control (free of toxin) and the 25 mg/kg bw/day or 100 mg/kg bw/day 3-epi-DON treatments in body and organ weights, hematology and organ histopathology. However, in mice exposed to DON (2 mg/kg bw/day), white blood cell numbers and serum immunoglobulin levels were altered relative to controls, and lesions were observed in adrenals, thymus, stomach, spleen and colon. Taken together, in vitro and in vivo studies indicate that 3-epi-DON is substantially less toxic than DON. PMID- 26363309 TI - Urban Adolescents' and Young Adults' Decision-Making Process around Selection of Intrauterine Contraception. AB - STUDY OBJECTIVE: To examine adolescent and young adults' priorities, values, and preferences affecting the choice to use an intrauterine contraceptive device (IUD). DESIGN: Qualitative exploratory study with analysis done using a modified grounded theory approach. SETTING: Outpatient adolescent medicine clinic located within an academic children's hospital in the Bronx, New York. PARTICIPANTS: Twenty-seven women aged 16 to 25 years of age on the day of their IUD insertion. INTERVENTIONS AND MAIN OUTCOME MEASURES: We conducted semistructured interviews exploring participant's decision making process around selecting an IUD. We were specifically interested in elucidating factors that could potentially improve IUD counseling. RESULTS: We identified 4 broad factors affecting choice: (1) personal; (2) IUD device-specific; (3) health care provider; and (4) social network. Most of the participants perceived an ease with a user-independent method and were attracted by the high efficacy of IUDs, potential longevity of use, and the option to remove the device before its expiration. Participants described their health care provider as being the most influential individual during the IUD decision-making process via provision of reliable, accurate contraceptive information and demonstration of an actual device. Of all people in their social network, mothers played the biggest role. CONCLUSION: Adolescents and young women who choose an IUD appear to value the IUDs' efficacy and convenience, their relationship with and elements of clinicians' contraceptive counseling, and their mother's support. Our results suggest that during IUD counseling, clinicians should discuss these device-specific benefits, elicit patient questions and concerns, and use visual aids including the device itself. Incorporating the factors we found most salient into routine IUD counseling might increase the number of adolescents and young women who choose an IUD as a good fit for them. PMID- 26363310 TI - In-vivo administration of clozapine affects behaviour but does not reverse dendritic spine deficits in the 14-3-3zeta KO mouse model of schizophrenia-like disorders. AB - Clozapine is an atypical antipsychotic drug used in the treatment of schizophrenia, which has been shown to reverse behavioural and dendritic spine deficits in mice. It has recently been shown that deficiency of 14-3-3zeta has an association with schizophrenia, and that a mouse model lacking this protein displays several schizophrenia-like behavioural deficits. To test the effect of clozapine in this mouse model, 14-3-3zeta KO mice were administered clozapine (5mg/kg) for two weeks prior to being analysed in a test battery of cognition, anxiety, and despair (depression-like) behaviours. Following behavioural testing brain samples were collected for analysis of specific anatomical defects and dendritic spine formation. We found that clozapine reduced despair behaviour of 14-3-3zeta KO mice in the forced swim test (FST) and altered the behaviour of wild types and 14-3-3zeta KO mice in the Y-maze task. In contrast, clozapine had no effects on hippocampal laminar defects or decreased dendritic spine density observed in 14-3-3zeta KO mice. Our results suggest that clozapine may have beneficial effects on clinical behaviours associated with deficiencies in the 14 3-3zeta molecular pathway, despite having no effects on morphological defects. These findings may provide mechanistic insight to the action of this drug. PMID- 26363311 TI - Atypical antipsychotic properties of AD-6048, a primary metabolite of blonanserin. AB - Blonanserin is a new atypical antipsychotic drug that shows high affinities to dopamine D2 and 5-HT2 receptors; however, the mechanisms underlying its atypicality are not fully understood. In this study, we evaluated the antipsychotic properties of AD-6048, a primary metabolite of blonanserin, to determine if it contributes to the atypicality of blonanserin. Subcutaneous administration of AD-6048 (0.3-1mg/kg) significantly inhibited apomorphine (APO) induced climbing behavior with an ED50 value of 0.200mg/kg, the potency being 1/3 1/5 times that of haloperidol (HAL). AD-6048 did not cause extrapyramidal side effects (EPS) even at high doses (up to 10mg/kg, s.c.), whereas HAL at doses of 0.1-3mg/kg (s.c.) significantly induced bradykinesia and catalepsy in a dose dependent manner. Thus, the therapeutic index (potency ratios of anti-APO action to that of EPS induction) of AD-6048 was much higher than that of haloperidol, illustrating that AD-6048 per se possesses atypical antipsychotic properties. In addition, immunohistochemical analysis of Fos protein expression revealed that both AD-6048 and HAL significantly increased Fos expression in the shell part of the nucleus accumbens and the striatum. However, in contrast to HAL which preferentially enhanced striatal Fos expression, AD-6048 showed a preferential action to the nucleus accumbens. These results indicate that AD-6048 acts as an atypical antipsychotic, which seems to at least partly contribute to the atypicality of blonanserin. PMID- 26363312 TI - Acute opioid administration induces hypothalamic-pituitary-adrenal activation and is mediated by genetic variation in interleukin (Il)1B. AB - There is a complex relationship between drug dependence and stress, with alcohol and other drugs of abuse both relieving stress and potentially inducing physiological stress responses in the user. Opioid drugs have been shown to modulate hypothalamic-pituitary-adrenal (HPA) activity in animal models and individual response to this modulation may play a role in continuation of drug use. Healthy young Caucasian adults were administered a single dose of immediate release oxycodone (20mg, n=30) or assigned to a control group (n=19) that was not administered the drug. At 0, 1, 2, 4 and 6h post-administration, blood and saliva samples were collected along with assessment of pupil diameter. The HPA response was determined by measurement of salivary cortisol through a commercially available enzyme-linked immunosorbent assay (ELISA). The results were compared to genotype at the -511 and -31 positions in the interleukin1B (IL1B) gene. No difference in cortisol production was initially observed between the two groups, however, when participants were separated based on their genotype for two single nucleotide polymorphisms in the promoter of the IL1B gene, which have been shown to occur at a higher frequency in opioid-dependent populations, individuals carrying the -511T and -31 C alleles (-511 C/T, -31 C/T or -511 T/T, -31 C/C) had a significantly (p<0.05) higher cortisol levels compared to individuals homozygous for the -511 C and -31T alleles. These results suggest that individuals carrying the -511T and -31 C alleles experience HPA activation in response to opioid administration and therefore may be less likely to undertake subsequent self-administration. PMID- 26363313 TI - The nitric oxide donor molsidomine induces anxiolytic-like behaviour in two different rat models of anxiety. AB - Experimental evidence indicates the implication of the nitric oxide (NO) in anxiety. Contradictory results were reported however, concerning the effects of NO donors in animal models of anxiety disorders. The present study investigated the effects of the NO donor molsidomine on anxiety-like behaviour and compared them with the anxiolytic diazepam in rats. For this purpose, the light/dark and the open field tests were used. The effects of molsidomine on motility were also assessed. Intraperitoneal (i.p.) administration of molsidomine (1 and 4mg/kg) did not influence rats' performance either in the light/dark or in the open field test. Administration of 2mg/kg molsidomine significantly prolonged the time spent in the light chamber in the rats compared with the vehicle-treated animals, did not affect the first latency to enter the dark chamber and did not influence the number of transitions between the light and dark compartments of the apparatus. In the open field test, rats that received 2mg/kg molsidomine spent more time in the central zone of the apparatus and exhibited an increment of rearing episodes compared with control and to molsidomine 1 and 4mg/kg-treated rats. Nevertheless, molsidomine, at any dose tested, did not alter locomotor activity compared with vehicle-treated rats in a motility test. The present results indicate that the 2mg/kg molsidomine induced anxiolytic-like effects in the light/dark and open field tests in the rat cannot be attributed to changes in locomotor activity. The magnitude of the molsidomine (2mg/kg)-induced anxiolytic-like effects was not different to that produced by the benzodiazepine anxiolytic diazepam (1mg/kg). PMID- 26363314 TI - Low dose EGCG treatment beginning in adolescence does not improve cognitive impairment in a Down syndrome mouse model. AB - Down syndrome (DS) or Trisomy 21 causes intellectual disabilities in humans and the Ts65Dn DS mouse model is deficient in learning and memory tasks. DYRK1A is triplicated in DS and Ts65Dn mice. Ts65Dn mice were given up to ~20mg/kg/day epigallocatechin-3-gallate (EGCG), a Dyrk1a inhibitor, or water beginning on postnatal day 24 and continuing for three or seven weeks, and were tested on a series of behavioral and learning tasks, including a novel balance beam test. Ts65Dn as compared to control mice exhibited higher locomotor activity, impaired novel object recognition, impaired balance beam and decreased spatial learning and memory. Neither EGCG treatment improved performance of the Ts65Dn mice on these tasks. Ts65Dn mice had a non-significant increase in Dyrk1a activity in the hippocampus and cerebellum. Given the translational value of the Ts65Dn mouse model, further studies will be needed to identify the EGCG doses (and mechanisms) that may improve cognitive function. PMID- 26363316 TI - An efficient and green pretreatment to stimulate short-chain fatty acids production from waste activated sludge anaerobic fermentation using free nitrous acid. AB - Short-chain fatty acid (SCFA) production from waste activated sludge (WAS) anaerobic fermentation is often limited by the slow hydrolysis rate and poor substrate availability, thus a long fermentation time is required. This paper reports a new pretreatment approach, i.e., using free nitrous acid (FNA) to pretreat sludge, for significantly enhanced SCFA production. Experimental results showed the highest SCFA production occurred at 1.8 mg FNA/L with time of day 6, which was 3.7-fold of the blank at fermentation time of day 12. Mechanism studies revealed that FNA pretreatment accelerated disruption of both extracellular polymeric substances and cell envelope. It was also found that FNA pretreatment benefited hydrolysis and acidification processes but inhibited the activities of methanogens, thereby promoting the yield of SCFA. In addition, the FNA pretreatment substantially stimulated the activities of key enzymes responsible for hydrolysis and acidification, which were consistent with the improvement of solubilization, hydrolysis and acidification of WAS anaerobic fermentation. PMID- 26363315 TI - Repositioning antipsychotic chlorpromazine for treating colorectal cancer by inhibiting sirtuin 1. AB - Investigating existing drugs for repositioning can enable overcoming bottlenecks in the drug development process. Here, we investigated the effect and molecular mechanism of the antipsychotic drug chlorpromazine (CPZ) and identified its potential for treating colorectal cancer (CRC). Human CRC cell lines harboring different p53 statuses were used to investigate the inhibitory mechanism of CPZ. CPZ effectively inhibited tumor growth and induced apoptosis in CRC cells in a p53-dependent manner. Activation of c-jun N-terminal kinase (JNK) was crucial for CPZ-induced p53 expression and the subsequent induction of tumor apoptosis. Induction of p53 acetylation at lysine382 was involved in CPZ-mediated tumor apoptosis, and this induction was attenuated by sirtuin 1 (SIRT1), a class III histone deacetylase. By contrast, knocking down SIRT1 sensitized tumor cells to CPZ treatment. Moreover, CPZ induced the degradation of SIRT1 protein participating downstream of JNK, and JNK suppression abrogated CPZ-mediated SIRT1 downregulation. Clinical analysis revealed a significant association between high SIRT1 expression and poor outcome in CRC patients. These data suggest that SIRT1 is an attractive therapeutic target for CRC and that CPZ is a potential repositioned drug for treating CRC. PMID- 26363317 TI - Cadmium exposure to murine macrophages decreases their inflammatory responses and increases their oxidative stress. AB - Cadmium (Cd) is an environmental contaminant that poses serious risks to human and wildlife health. The oxidative stress and inflammatory responses induced by Cd were evaluated in RAW264.7 cells. A significant decrease in the cell viability was observed in the group treated with 3 uM Cd for 24 h. The mRNA levels of tumor necrosis factor-alpha (TNFalpha), interleukin-6 (IL6), interleukin-1alpha (IL1alpha) and Interleukin-1beta (IL1beta) were generally increased or decreased by Cd exposure for 6 and 24 h, respectively. Moreover, pretreatment of the RAW264.7 cells with Cd for 24 h inhibited the transcriptional status of TNFalpha, IL6, IL1alpha and IL1beta and the release of these cytokines in response to a 6-h lipopolysaccharide (LPS) treatment in a dose-dependent manner. Furthermore, the Cd exposure elicited oxidative stress not only by disturbing the transcriptional status of genes including superoxide dismutase (Sod), catalase (Cat), glutathione peroxidase(Gpx), glutathione S-transferase 1 a (Gst1a), NAD(P)H: quinone oxidoreductase 1(Nqo1), heme oxygenase 1(Ho-1) but also the enzyme activities of SOD, CAT and glutathione S-transferase (GST). The effects of Cd on the mRNA levels and activities of anti-oxidative enzymes were dependent on the exposure period and dose. These results suggested that Cd exposure generated oxidative stress and decreased the inflammatory responses in a murine macrophage cell line. Furthermore, oxidative stress may be a possible mechanism to explain the dysregulation of the immune function caused by heavy metals in this in vitro system. PMID- 26363318 TI - Insights into the degradation of chlorimuron-ethyl by Stenotrophomonas maltophilia D310-3. AB - In this study, the effects of cultivation conditions on the degradation of chlorimuron-ethyl by Stenotrophomonas maltophilia D310-3, which exhibits a high chlorimuron-ethyl-degrading capability, were investigated. To improve the biodegradation efficiency, the cultivation conditions were optimized using response surface methodology (RSM) based on Box-Behnken design (BBD). The maximum biodegradation rate (89.9%) was obtained at the optimal conditions (culture time, 6 d; substrate concentration, 50.21 mg L(-1); pH, 5.95; temperature, 30.15 degrees C). The Andrews model was used to describe the dynamic change regularity of the specific degradation rate as the substrate concentration increased, and the values of the maximum specific degradation rate (q(max)), half-saturation constant (K(S)) and inhibition constant (K(i)) were 78.87 d(-1), 9180.97 mg L(-1) and 0.28 mg L(-1), respectively. Eight degradation products were captured and identified by liquid chromatography-mass spectrometry (LC-MS) and Fourier transform infrared (FTIR) spectrometry, and three possible degradation pathways are proposed based on the results of high-performance liquid chromatography (HPLC), LC-MS and FTIR analyses as well as results reported in relevant literature. To the best of our knowledge, this is the first systematic study of the degradation pathway of chlorimuron-ethyl by S. maltophilia D310-3. This study provides valuable information for further exploration of the microbial degradation of other sulfonylurea herbicides. PMID- 26363319 TI - Biomagnification of endocrine disrupting chemicals (EDCs) by Pleuronectes yokohamae: Does P. yokohamae accumulate dietary EDCs? AB - We evaluated the potential for biomagnification of endocrine disrupting chemicals (EDCs) such as nonylphenol (NP), octylphenol (OP), bisphenol A (BP), and natural estrogens such as estrone (E1) and 17beta-estradiol (E2) in a benthic fish, Pleuronectes yokohamae. The assimilation efficiencies (AE) of most EDCs ranged from 88 to 96% suggesting that they were efficiently incorporated and assimilated into P. yokohamae, except for NP (50%). However, the biomagnification factor (BMF) values were <1.0 suggesting that the compounds were not biomagnifying. Additionally, three of the target EDCs were not detected (BP, E1 and E2). Glucuronidation activity towards BP (11.44 +/- 2.5 nmol/mg protein/min) and E2 (12.41 +/- 3.2 nmol/mg protein/min) was high in the intestine suggesting that EDCs were glucuronidated prior to excretion into bile. Thus, we conclude that biomagnification of dietary EDCs is reduced in P. yokohamae because of effective glucuronidation. PMID- 26363320 TI - Ecotoxicogenomics: Microarray interlaboratory comparability. AB - Transcriptomic analysis can complement traditional ecotoxicology data by providing mechanistic insight, and by identifying sub-lethal organismal responses and contaminant classes underlying observed toxicity. Before transcriptomic information can be used in monitoring and risk assessment, it is necessary to determine its reproducibility and detect key steps impacting the reliable identification of differentially expressed genes. A custom 15K-probe microarray was used to conduct transcriptomics analyses across six laboratories with estuarine amphipods exposed to cyfluthrin-spiked or control sediments (10 days). Two sample types were generated, one consisted of total RNA extracts (Ex) from exposed and control samples (extracted by one laboratory) and the other consisted of exposed and control whole body amphipods (WB) from which each laboratory extracted RNA. Our findings indicate that gene expression microarray results are repeatable. Differentially expressed data had a higher degree of repeatability across all laboratories in samples with similar RNA quality (Ex) when compared to WB samples with more variable RNA quality. Despite such variability a subset of genes were consistently identified as differentially expressed across all laboratories and sample types. We found that the differences among the individual laboratory results can be attributed to several factors including RNA quality and technical expertise, but the overall results can be improved by following consistent protocols and with appropriate training. PMID- 26363321 TI - Dissipation and distribution of chlorpyrifos in selected vegetables through foliage and root uptake. AB - Dissipation, distribution and uptake pathways of chlorpyrifos were investigated in pakchoi (Brassica chinensis L.) and lettuce (Lactuca sativa) with foliage treatments under a greenhouse trial and root treatments under a hydroponic experiment. The dissipation trends were similar for chlorpyrifos in pakchoi and lettuce with different treatments. More than 94% of chlorpyrifos was degraded in the samples for both of the vegetables 21 days after the foliage treatments. For the root treatment, the dissipation rate of chlorpyrifos in pakchoi and lettuce at the low concentration was greater than 93%, however, for the high concentrations, the dissipation rates were all under 90%. Both shoots and roots of the vegetables were able to absorb chlorpyrifos from the environment and distribute it inside the plants. Root concentration factor (RCF) values at different concentrations with the hydroponic experiment ranged from 5 to 39 for pakchoi, and from 14 to 35 for lettuce. The translocation factor (TF) representing the capability of the vegetables to translocate contaminants was significantly different for pakchoi and lettuce with foliage and root treatments. The values of TF with foliage treatments ranged from 0.003 to 0.22 for pakchoi, and from 0.032 to 1.63 for lettuce. The values of TF with root treatments ranged from 0.01 to 0.17 for pakchoi, and from 0.003 to 0.23 for lettuce. Significant difference of TF was found between pakchoi and lettuce with foliage treatments, and at high concentrations (10 and 50 mg L(-1)) with root treatments as well. However, there was no significant difference of TF between pakchoi and lettuce at 1 mg L(-1) with root treatment. PMID- 26363322 TI - Amphetamine exposure imbalanced antioxidant activity in the bivalve Dreissena polymorpha causing oxidative and genetic damage. AB - Illicit drugs have been recognized as emerging aquatic pollutants due to their presence in aquatic ecosystems up to ug/L level. Among these, the synthetic psycho-stimulant drug amphetamine (AMPH) is commonly found in both surface and wastewaters worldwide. Even though the environmental occurrence of AMPH is well known, the information on its toxicity towards non-target freshwater organisms is completely lacking. This study investigated the imbalance of the oxidative status and both oxidative and genetic damage induced by a 14-day exposure to two concentrations (500 ng/L and 5000 ng/L) of AMPH on the freshwater bivalve Dreissena polymorpha by the application of a biomarker suite. We investigated the activity of antioxidant enzymes (SOD, CAT and GPx), the phase II detoxifying enzyme GST, the lipid peroxidation level (LPO) and protein carbonyl content (PCC), as well as primary (Single Cell Gel Electrophoresis assay) and fixed (DNA diffusion assay and Micronucleus test) genetic damage. Our results showed that a current realistic AMPH concentration (500 ng/L) did neither cause notable imbalances in enzymatic activities, nor oxidative and genetic damage to cellular macromolecules. In contrast, the bell-shaped trend of antioxidants showed at the highest tested concentration (5000 ng/L) suggested an overproduction of reactive oxygen species, leading to oxidative damage, as confirmed by the significant increase of protein carbonylation and DNA fragmentation. PMID- 26363323 TI - Toxicological effects of benzo(a)pyrene, DDT and their mixture on the green mussel Perna viridis revealed by proteomic and metabolomic approaches. AB - Benzo(a)pyrene (BaP) and dichlorodiphenyltrichloroethane (DDT) are persistent organic pollutants and environmental estrogens (EEs) with known toxicity towards the green mussel, Perna viridis. In this study, the toxic effects of BaP (10 ug/L) and DDT (10 ug/L) and their mixture were assessed in green mussel gills with proteomic and metabolomic approaches. Metabolic responses indicated that BaP mainly caused disturbance in osmotic regulation by significantly decrease in branched chain amino acids, dimethylamine and dimethylglycine in gills of male green mussels after exposure for 7 days. DDT mainly caused disturbance in osmotic regulation and energy metabolism by differential alteration of betaine, dimethylamine, dimethylglycine, amino acids, and succinate in gills of male green mussels. However, the mixture of BaP and DDT didn't show obvious metabolite changes. Proteomic analysis showed different protein expression profiles between different treatment groups, which demonstrated that BaP, DDT and their mixture may have different modes of action. Proteomic responses revealed that BaP induced cell apoptosis, disturbance in protein digestion and energy metabolism in gills of green mussels, whereas DDT exposure altered proteins that were associated with oxidative stress, cytoskeleton and cell structure, protein digestion and energy metabolism. However, the mixture of BaP and DDT affected proteins related to the oxidative stress, cytoskeleton and cell structure, protein biosynthesis and modification, energy metabolism, growth and apoptosis. PMID- 26363324 TI - Heavy metals produce toxicity, oxidative stress and apoptosis in the marine teleost fish SAF-1 cell line. AB - The use of cell lines to test the toxicity of aquatic pollutants is a valuable alternative to fish bioassays. In this study, fibroblast SAF-1 cells from the marine gilthead seabream (Sparus aurata L.) were exposed for 24 h to the heavy metals Cd, Hg, MeHg (Methylmercury), As or Pb and the resulting cytotoxicity was assessed. Neutral red (NR), MTT-tetrazolio (MTT), crystal violet (CV) and lactate dehydrogenase (LDH) viability tests showed that SAF-1 cells exposed to the above heavy metals produced a dose-dependent reduction in the number of viable cells. Methylmercury showed the highest toxicity (EC50 = 0.01 mM) followed by As, Cd, Hg and Pb. NR was the most sensitive method followed by MTT, CV and LDH. SAF-1 cells incubated with each of the heavy metals also exhibited an increase in the production of reactive oxygen species and apoptosis cell death. Moreover, the corresponding gene expression profiles pointed to the induction of the metallothionein protective system, cellular and oxidative stress and apoptosis after heavy metal exposure for 24 h. This report describes and compares tools for evaluating the potential effects of marine contamination using the SAF-1 cell line. PMID- 26363325 TI - Oxidative stress, DNA damage and antioxidant enzyme activities in the pacific white shrimp (Litopenaeus vannamei) when exposed to hypoxia and reoxygenation. AB - To evaluate the genotoxic and physiological effects of acute hypoxia on the pacific white shrimp (L. vannamei), shrimps were treated firstly with three dissolved oxygen levels 6.5 ppm (control), 3.0 ppm and 1.5 ppm for 24 h, respectively, and then reoxygenated (6.5 ppm) for 24 h. The changes of superoxide dismutase (SOD) activity, glutathione peroxidases (GPX) activity, malondialdehyde (MDA) concentration and DNA damage in the tissues of gill, hepatopancreas and hemolymph were examined during the period of hypoxia and reoxygenation. The results indicated SOD activity, GPX activity, MDA concentration and DNA damage all increased basically compared with the control during the period of hypoxia except for MDA concentrations in the gill at 12 h and 24 h hypoxia (3.0 ppm), and these parameters were recovered to some degree during the period of reoxygenation. Moreover, the comet assays in the tissues of gill and hepatopancreas showed an obvious time- and dose-dependent response to hypoxia, which indicated comet assay in the two tissues could be used as sensitive biomarker to detect the occurrence of hypoxia. We conclude that acute hypoxia can induce oxidative stress, DNA damage and lipid peroxidation in the tissues of gill, hepatopancreas and hemolymph of L. vannamei and the DNA damage may come from hypoxia-induced oxidative stress. PMID- 26363326 TI - Laboratory study of the particle-size distribution of Decabromodiphenyl ether (BDE-209) in ambient air. AB - Laboratory measurements for particle-size distribution of Decabromodiphenyl ether (BDE-209) were performed in a 0.5 m(3) sealed room at 25 degrees C. BDE-209 was manually bounded to ambient particles. An electrostatic field-sampler was employed to collect particles. The number of collected particles (n(i,j), i and j was the class of particle diameter and applied voltage on electrostatic field sampler sampler, respectively) and the corresponding mass of BDE-209 in collected particles (m(?i,j)) were determined in a series of 6 experiments. The particle size distribution coefficient (ki) was calculated through equations related to n(i,j) and m(?i,j), and the particle-size distribution of BDE-209 was determined by ki.n(i,j). Results revealed that BDE-209 distributed in particles of all size and were not affiliated with fine particles as in field measurements. The particle size-fraction should be taken into account when discussing the particle size distribution of BDE-209 in ambient air due to the normalized coefficients (normalized to k1) and were approximately in the same order of magnitude for each diameter class. The method described in the present study was deemed feasible in determining the particle-size distribution of BDE-209 from vaporization sources and helpful to understanding the instinct rule of particle-size distribution of BDE-209, and potentially feasible for other SVOCs. PMID- 26363327 TI - Long term performance of membranes in an anaerobic membrane bioreactor treating municipal wastewater. AB - The long term impact of SRT (100-40 days) and recovery cleaning on membrane performance of an AnMBR treating authentic municipal wastewater in a large pilot plant was assessed. Successful operation of the pilot plant at a flux of 17 LMH was maintained for a period of 536 days during which the longest period of operation without recovery cleaning or membrane replacement was 178 days. Lower SRT (40 days) reduced the fouling propensity of the mixed liquor in terms of TSS concentration and the dewaterability indicators including colloidal COD (cCOD) concentration and capillary suction time (CST). Critical fluxes ranged from 21 to 23 LMH to 25-27 LMH for SRTs of 70 and 40 days respectively and this was consistent with the reduced concentrations of TSS and improved dewaterability under the latter conditions. Recovery cleaning was found to result in substantial reduction of resistance as indicated by both pilot plant operation and clean water flux tests. The long-term fouling rate was observed to be higher with cleaned membranes as compared to virgin membranes. The lower membrane fouling with virgin membranes suggested that accumulation of foulants, which were resistant to cleaning, caused the higher fouling rates for the cleaned membranes. PMID- 26363328 TI - Novel process of bio-chemical ammonia removal from air streams using a water reflux system and zeolite as filter media. AB - A novel biofilter that removes ammonia from air streams and converts it to nitrogen gas has been developed and operated continuously for 300 days. The ammonia from the incoming up-flow air stream is first absorbed into water and the carrier material, zeolite. A continuous gravity reflux of condensed water from the exit of the biofilter provides moisture for nitrifying bacteria to develop and convert dissolved ammonia (ammonium) to nitrite/nitrate. The down-flow of the condensed water reflux washes down nitrite/nitrate preventing ammonium and nitrite/nitrate accumulation at the top region of the biofilter. The evaporation caused by the inflow air leads to the accumulation of nitrite to extremely high concentrations in the bottom of the biofilter. The high nitrite concentrations favour the spontaneous chemical oxidation of ammonium by nitrite to nitrogen (N2). Tests showed that this chemical reaction was catalysed by the zeolite filter medium and allowed it to take place at room temperature. This study shows that ammonia can be removed from air streams and converted to N2 in a fully aerated single step biofilter. The process also overcomes the problem of microorganism-inhibition and resulted in zero leachate production. PMID- 26363329 TI - Assessment of heavy metals contamination in sediments from three adjacent regions of the Yellow River using metal chemical fractions and multivariate analysis techniques. AB - Metal chemical fractions obtained by optimized BCR three-stage extraction procedure and multivariate analysis techniques were exploited for assessing 7 heavy metals (Cr, Pb, Cd, Co, Cu, Zn and Ni) in sediments from Gansu province, Ningxia and Inner Mongolia Autonomous Regions of the Yellow River in Northern China. The results indicated that higher susceptibility and bioavailability of Cr and Cd with a strong anthropogenic source were due to their higher availability in the exchangeable fraction. A portion of Pb, Cd, Co, Zn, and Ni in reducible fraction may be due to the fact that they can form stable complexes with Fe and Mn oxides. Substantial amount of Pb, Co, Ni and Cu was observed as oxidizable fraction because of their strong affinity to the organic matters so that they can complex with humic substances in sediments. The high geo-accumulation indexes (I(geo)) for Cr and Cd showed their higher environmental risk to the aquatic biota. Principal component analysis (PCA) revealed that high toxic Cr and Cd in polluted sites (Cd in S10, S11 and Cr in S13) may be contributed to anthropogenic sources, it was consistent with the results of dual hierarchical clustering analysis (DHCA), which could give more details about contributing sources. PMID- 26363330 TI - Comment on "Halogenated indigo dyes: A likely source of 1,3,6,8 tetrabromocarbazole and some other halogenated carbazoles in the environment". PMID- 26363331 TI - EUS-guided ethanol lavage does not reliably ablate pancreatic cystic neoplasms (with video). AB - BACKGROUND: The true efficacy of EUS-guided ethanol lavage (EEL) of pancreatic cystic neoplasms is unclear. This study aimed to assess long-term outcomes and adverse events of EEL by using a standardized protocol. METHODS: Single-center, prospective, pilot study in which participants with suspected mucinous cyst neoplasms or branch duct intraductal papillary mucinous neoplasms >=1 cm in maximum diameter underwent EEL with 80% ethanol. Follow-up cross-sectional imaging was obtained to assess for changes in cyst volume. RESULTS: Twenty-three patients underwent EEL (57% male, mean age 70 years). Mean duration of follow-up was 40 months (range 9-82 months). Mean calculated final concentration of ethanol achieved in treated cysts was 50% (range 0%-79%). Complete resolution of pancreatic cystic neoplasms occurred in 2 participants (9%). When stratified into those participants who achieved >=80% versus <80% reduction in cyst volume, no statistically significant differences were seen with regard to patient demographics, cyst characteristics, or final concentration of ethanol achieved in the treated cyst. Greater decreases in cyst volume were seen in presumed nonmucinous cysts compared with presumed mucinous cysts (P = .006). Two early adverse events occurred. Five participants died during the study follow-up period (4 from nonpancreatic causes), including 1 participant who was diagnosed with pancreatic adenocarcinoma thought to have arisen from the treated branch duct intraductal papillary mucinous neoplasm 41 months after undergoing EEL. CONCLUSIONS: As performed in this study, EEL therapy does not appear to be a promising method for prevention of malignancy in pancreatic cysts. Endoscopic methods that effectively and completely ablate pancreatic cystic neoplasms are needed. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT02158039.). PMID- 26363332 TI - Randomized, double-blind trial of CO2 versus air insufflation in children undergoing colonoscopy. AB - BACKGROUND AND AIMS: Studies in adults have shown that postprocedural abdominal pain is reduced with the use of carbon dioxide (CO(2)) instead of air for insufflation during colonoscopy. The aim of our study was to compare postprocedural abdominal pain and girth in children undergoing colonoscopy using CO(2) or air for insufflation. METHODS: This was a prospective, randomized, double-blind study that included 76 consecutive pediatric patients undergoing colonoscopy for various indications. Patients were randomly assigned to either CO(2) or air insufflation. At 2, 4, and 24 hours after the examination, the patients' pain was assessed by using the 11-point numerical rating scale. The waist circumference was measured 10 minutes and 2 and 4 hours after colonoscopy. RESULTS: A significantly higher proportion of patients had no pain after colonoscopy in the CO(2) group compared with the air group (82 vs 37% at 2 hours and 95% vs. 63% at 4 hours, P < .001). Mean abdominal pain scores 2 and 4 hours after the procedure were statistically significantly lower in the CO(2) group compared with the control air group (0.5 vs 2.6 at 2 hours and 0.1 vs 1.2 at 4 hours, P < .001). There was no difference in waist circumference between the 2 groups at all time intervals. CONCLUSION: The results of this randomized trial show clear benefits of CO(2) insufflation for colonoscopy in reducing postprocedural discomfort. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT02407639.). PMID- 26363333 TI - A phase IIb study comparing the safety and efficacy of remimazolam and midazolam in patients undergoing colonoscopy. AB - BACKGROUND AND AIMS: Remimazolam is an ultra-short-acting benzodiazepine currently being developed for procedural sedation and for induction and maintenance of anesthesia. This trial was the fourth study for procedural sedation. The aim was to compare the safety and efficacy profile of remimazolam and to refine suitable doses for subsequent phase III studies in this indication. METHODS: This was a randomized, double-blind, parallel group, active controlled clinical trial with 162 male and female patients, aged 18 to 70, scheduled to undergo a routine colonoscopy. Patients were randomized to receive 1 of 3 remimazolam doses or midazolam for sedation. Supplemental oxygen and 100 MUg of fentanyl was given before procedures were started, and the colonoscopy commenced as soon as suitable sedation had been achieved (Modified Observer's Assessment of Alertness/Sedation score <=3). Top-up doses of the study drug and/or fentanyl were allowed to maintain suitable sedation and/or analgesia. Response was defined as sufficient sedation, no rescue sedative, and no ventilation required. RESULTS: This study showed that a single dose of remimazolam or midazolam, followed by top up doses to maintain suitable sedation, provided adequate sedation with a high success rate (>92%) for the remimazolam groups, compared with 75% for the midazolam group (P = .007). There was no requirement for mechanical ventilation in any group, and procedure failures were all due to use of rescue sedative. CONCLUSIONS: The high success rates and good safety profile of remimazolam observed in this study warrants further investigation and confirmation in phase III trials. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT01145222.). PMID- 26363334 TI - Colon capsule endoscopy compared with other modalities in the evaluation of pediatric Crohn's disease of the small bowel and colon. AB - BACKGROUND AND AIMS: Data on colon capsule endoscopy (CCE) in evaluating the small bowel and colon concurrently are rare. This study aimed to evaluate the accuracy of CCE in assessing disease activity of the small bowel and colon in pediatric Crohn's disease (CD) by comparison with magnetic resonance enterography (MRE), small-intestine contrast US (SICUS), and ileocolonoscopy. METHODS: We prospectively enrolled 40 consecutive patients (22 male, 18 female, mean age 13.1 +/- 3.1 years) with CD of the small bowel and colon. All underwent SICUS, MRE, CCE, and ileocolonoscopy sequentially over 5 days. All investigators were blinded to patient history and test results. Patients were classified as active or inactive for the small bowel and the colon according to specific criteria for each tool (simple endoscopic score for CD, Lewis score, US and magnetic resonance parameters of activity). For colon mucosa evaluation, ileocolonoscopy was the comparator. For the small bowel, a consensus panel was convened. RESULTS: Sensitivity of CCE to detect colon inflammation was 89%, and specificity was 100%. The positive predictive value (PPV) and negative predictive value (NPV) of CCE for colon inflammation were 100% and 91%, respectively. In the small bowel, CCE showed 90% sensitivity, 94% specificity, with PPV and NPV of 95% and 90%, respectively. Accuracy parameters for SICUS (sensitivity 90%, specificity 83%) and MRE (sensitivity 85%, specificity 89%) were lower than those for CCE. No serious adverse events related to the CCE procedure or preparation were reported. CONCLUSIONS: CCE is of great usefulness in evaluating both small bowel and colon mucosa in pediatric CD. This single, noninvasive tool makes it possible to evaluate the small-bowel and the colon concurrently with high diagnostic accuracy. Future multicenter studies need to define the role of CCE in the routine management of pediatric patients with CD. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT02199626.). PMID- 26363335 TI - Effective equations for anisotropic glioma spread with proliferation: a multiscale approach and comparisons with previous settings. AB - Glioma is a common type of primary brain tumour, with a strongly invasive potential, often exhibiting non-uniform, highly irregular growth. This makes it difficult to assess the degree of extent of the tumour, hence bringing about a supplementary challenge for the treatment. It is therefore necessary to understand the migratory behaviour of glioma in greater detail. In this paper, we propose a multiscale model for glioma growth and migration. Our model couples the microscale dynamics (reduced to the binding of surface receptors to the surrounding tissue) with a kinetic transport equation for the cell density on the mesoscopic level of individual cells. On the latter scale, we also include the proliferation of tumour cells via effects of interaction with the tissue. An adequate parabolic scaling yields a convection-diffusion-reaction equation, for which the coefficients can be explicitly determined from the information about the tissue obtained by diffusion tensor imaging (DTI). Numerical simulations relying on DTI measurements confirm the biological findings that glioma spread along white matter tracts. PMID- 26363336 TI - Clinical Functional Capacity Testing in Patients With Facioscapulohumeral Muscular Dystrophy: Construct Validity and Interrater Reliability of Antigravity Tests. AB - OBJECTIVE: To evaluate the construct validity and interrater reliability of 4 simple antigravity tests in a small group of patients with facioscapulohumeral muscular dystrophy (FSHD). DESIGN: Case-control study. SETTING: University medical center. PARTICIPANTS: Patients with various severity levels of FSHD (n=9) and healthy control subjects (n=10) were included (N=19). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: A 4-point ordinal scale was designed to grade performance on the following 4 antigravity tests: sit to stance, stance to sit, step up, and step down. In addition, the 6-minute walk test, 10-m walking test, Berg Balance Scale, and timed Up and Go test were administered as conventional tests. Construct validity was determined by linear regression analysis using the Clinical Severity Score (CSS) as the dependent variable. Interrater agreement was tested using a kappa analysis. RESULTS: Patients with FSHD performed worse on all 4 antigravity tests compared with the controls. Stronger correlations were found within than between test categories (antigravity vs conventional). The antigravity tests revealed the highest explained variance with regard to the CSS (R(2)=.86, P=.014). Interrater agreement was generally good. CONCLUSIONS: The results of this exploratory study support the construct validity and interrater reliability of the proposed antigravity tests for the assessment of functional capacity in patients with FSHD taking into account the use of compensatory strategies. Future research should further validate these results in a larger sample of patients with FSHD. PMID- 26363337 TI - The influence of lipid-containing plaque composition assessed by near-infrared spectroscopy on coronary lesion remodelling. AB - AIMS: Vessel remodelling is commonly observed in coronary atherosclerosis, but factors influencing remodelling, such as plaque lipid content, remain poorly described. METHODS AND RESULTS: Remodelling index (RI) was calculated as the ratio of lesion to proximal and distal references external membrane area and was categorized as follows: positive (PR; RI > 1.05), intermediate (IR; RI 0.95 1.05), and negative remodelling (NR; RI < 0.95). RI was studied by near-infrared spectroscopy (NIRS) as a function of lipid content metrics, including the maximal 4 mm lipid core burden index of the segment (maxLCBI4 mm) and intravascular ultrasound (IVUS) lesion plaque burden (PB). The authors further stratified the analysis according to obstructive (>=50%) and non-obstructive (<50%) lesions using quantitative coronary angiography. Receiver-operating characteristic curves were performed to describe the maxLCBI4 mm level associated with PR. From May 2012 to November 2014, 100 de novo lesions from 67 patients underwent simultaneous NIRS-IVUS. PR was found in 28% of the lesions. There was a positive linear correlation between RI and maxLCBI4 mm (rho = 0.58; P < 0.001). Although PR lesions had a larger PB than NR or IR (P < 0.001), the correlation of RI with maxLCBI4 mm was stronger compared with plaque volume (rho = 0.18; P = 0.07) and with per cent PB (rho = 0.41; P < 0.001). This relationship remained significant for obstructive (rho = 0.72; P < 0.001) and non-obstructive lesions (rho = 0.48; P < 0.001). By receiver-operating characteristic curve analysis, values of maxLCBI4 mm >= 439 were predictive for PR (area under the curve = 0.79, 95% confidence interval: 0.69-0.89). CONCLUSION: In vivo coronary lesion remodelling is positively correlated with lipid plaque content assessed by NIRS rather than simply PB. Thus, the use of NIRS can potentially aid in further stratifying vulnerable lesions. PMID- 26363338 TI - Sweet and brittle - Diabetes mellitus and the skeleton. PMID- 26363339 TI - Transplantation of hypoxia preconditioned bone marrow mesenchymal stem cells enhances angiogenesis and osteogenesis in rabbit femoral head osteonecrosis. AB - PURPOSE: Osteonecrosis of the femoral head may be a disease resulting from abnormal proliferation or differentiation of mesenchymal stem cells. The present investigation explored the novel strategy of hypoxia-preconditioned BMMSCs to reverse the impairment of osteonecrosis BMMSCs and enhance the therapeutic potential of hypoxia-treated BMMSC transplantation. METHODS: BMMSCs from the anterior superior iliac spine region of osteonecrosis rabbit were cultured under 20% O2 or 2% O2 conditions. Normal BMMSCs were cultured under 20% O2 condition as control. Growth factors secreted were examined by enzyme-linked immunosorbent assay. 20% O2 or 2% O2 BMMSCs were injected into the femoral head of rabbits after core decompression. Cell viability and apoptosis were assessed in vitro, and TUNEL staining of the femoral head was analyzed after transplantation. Angiogenesis (capillary-like structure formation, CD31 immunohistochemical staining and ink infusion angiography) and osteogenesis (Alizarin red-S staining, micro-CT scanning and OCN immunohistochemical staining) tests were conducted as well. RESULTS: 2% O2 exposure up-regulated growth factor secretion in BMMSCs. Apoptosis in 2% O2 group was lower when compared with that in 20% O2 osteonecrosis group. Cell viability in 2% O2 was significantly higher when compared with that in 20% O2 osteonecrosis group. Growth factor secretion, cell viability, apoptosis, capillary-like structure formation, Alizarin red-S staining, and ALP staining showed no difference between the 2% O2 BMMSC and normal BMMSC groups. Transplantation of 2% O2 versus 20% O2 mesenchymal stem cells after core decompression resulted in an increase in angiogenesis function and a decrease in local tissue apoptosis. Our study also found that osteogenesis function was improved after hypoxic stem cell transplantation. CONCLUSION: Hypoxic preconditioning of BMMSCs is an effective means of reversing the impairment of osteonecrosis BMMSCs, promoting their regenerative capability and therapeutic potential for the treatment of osteonecrosis. PMID- 26363340 TI - The direct pathway from the brainstem reticular formation to the cerebral cortex in the ascending reticular activating system: A diffusion tensor imaging study. AB - Precise evaluation of the ascending reticular activating system (ARAS) is important for diagnosis, prediction of prognosis, and management of patients with disorders of impaired consciousness. In the current study, we attempted to reconstruct the direct neural pathway between the brainstem reticular formation (RF) and the cerebral cortex in normal subjects, using diffusion tensor imaging (DTI). Forty-one healthy subjects were recruited for this study. DTIs were performed using a sensitivity-encoding head coil at 1.5Tesla with FMRIB Software Library. For connectivity of the brainstem RF, we used two regions of interest (ROIs) for the brainstem RF (seed ROI) and the thalamus and hypothalamus (exclusion ROI). Connectivity was defined as the incidence of connection between the brainstem RF and target brain regions at the threshold of 5 and 50 streamlines. Regarding the thresholds of 5 and 50, the brainstem RF showed high connectivity to the lateral prefrontal cortex (lPFC, 67.1% and 20.7%) and ventromedial prefrontal cortex (vmPFC, 50.0% and 18.3%), respectively. In contrast, the brainstem RF showed low connectivity to the primary motor cortex (31.7% and 3.7%), premotor cortex (24.4% and 3.7%), primary somatosensory cortex (23.2% and 2.4%), orbitofrontal cortex (17.1% and 7.3%), and posterior parietal cortex (12.2% and 0%), respectively. The brainstem RF was mainly connected to the prefrontal cortex, particularly lPFC and vmPFC. We believe that the methodology and results of this study would be useful to clinicians involved in the care of patients with impaired consciousness and researchers in studies of the ARAS. PMID- 26363341 TI - An emotional functioning item bank of 24 items for computerized adaptive testing (CAT) was established. AB - OBJECTIVE: To improve measurement precision, the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Group is developing an item bank for computerized adaptive testing (CAT) of emotional functioning (EF). The item bank will be within the conceptual framework of the widely used EORTC Quality of Life questionnaire (QLQ-C30). STUDY DESIGN AND SETTING: On the basis of literature search and evaluations by international samples of experts and cancer patients, 38 candidate items were developed. The psychometric properties of the items were evaluated in a large international sample of cancer patients. This included evaluations of dimensionality, item response theory (IRT) model fit, differential item functioning (DIF), and of measurement precision/statistical power. RESULTS: Responses were obtained from 1,023 cancer patients from four countries. The evaluations showed that 24 items could be included in a unidimensional IRT model. DIF did not seem to have any significant impact on the estimation of EF. Evaluations indicated that the CAT measure may reduce sample size requirements by up to 50% compared to the QLQ-C30 EF scale without reducing power. CONCLUSION: On the basis of thorough psychometric evaluations, we have established an EF item bank of 24 items. This will allow for more precise and flexible measurement of EF, while maintaining backward compatibility with the QLQ-C30 EF scale. PMID- 26363342 TI - Repeat infusion of autologous bone marrow cells in multiple sclerosis: protocol for a phase I extension study (SIAMMS-II). AB - INTRODUCTION: The 'Study of Intravenous Autologous Marrow in Multiple Sclerosis (SIAMMS)' trial was a safety and feasibility study which examined the effect of intravenous infusion of autologous bone marrow without myeloablative therapy. This trial was well tolerated and improvement was noted in the global evoked potential (GEP)--a neurophysiological secondary outcome measure recording speed of conduction in central nervous system pathways. The efficacy of intravenous delivery of autologous marrow in progressive multiple sclerosis (MS) will be examined in the phase II study the 'Assessment of Bone Marrow-Derived Cellular Therapy in Progressive Multiple Sclerosis (ACTiMuS; NCT01815632)'. In parallel with the 'ACTiMuS' study, the current study 'SIAMMS-II' will explore the feasibility of repeated, non-myeloablative autologous bone marrow-derived cell therapy in progressive MS. Furthermore, information will be obtained regarding the persistence or otherwise of improvements in conduction in central nervous system pathways observed in the original 'SIAMMS' study and whether these can be reproduced or augmented by a second infusion of autologous bone marrow-derived cells. METHODS AND ANALYSIS: An open, prospective, single-centre phase I extension study. The six patients with progressive MS who participated in the 'SIAMMS' study will be invited to undergo repeat bone marrow harvest and receive an intravenous infusion of autologous, unfractionated bone marrow as a day-case procedure. The primary outcome measure is the number of adverse events, and secondary outcome measures will include change in clinical rating scales of disability, GEP and cranial MRI. ETHICS AND DISSEMINATION: The study has UK National Research Ethics Committee approval (13/SW/0255). Study results will be disseminated via peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT01932593. PMID- 26363343 TI - Peptide Probes Reveal a Hydrophobic Steric Ratchet in the Anthrax Toxin Protective Antigen Translocase. AB - Anthrax toxin is a tripartite virulence factor produced by Bacillus anthracis during infection. Under acidic endosomal pH conditions, the toxin's protective antigen (PA) component forms a transmembrane channel in host cells. The PA channel then translocates its two enzyme components, lethal factor and edema factor, into the host cytosol under the proton motive force. Protein translocation under a proton motive force is catalyzed by a series of nonspecific polypeptide binding sites, called clamps. A 10-residue guest/host peptide model system, KKKKKXXSXX, was used to functionally probe polypeptide-clamp interactions within wild-type PA channels. The guest residues were Thr, Ala, Leu, Phe, Tyr, and Trp. In steady-state translocation experiments, the channel blocked most tightly with peptides that had increasing amounts of nonpolar surface area. Cooperative peptide binding was observed in the Trp-containing peptide sequence but not the other tested sequences. Trp substitutions into a flexible, uncharged linker between the lethal factor amino-terminal domain and diphtheria toxin A chain expedited translocation. Therefore, peptide-clamp sites in translocase channels can sense large steric features (like tryptophan) in peptides, and while these steric interactions may make a peptide translocate poorly, in the context of folded domains, they can make the protein translocate more rapidly presumably via a hydrophobic steric ratchet mechanism. PMID- 26363344 TI - When sentences live up to your expectations. AB - Speech recognition is rapid, automatic and amazingly robust. How the brain is able to decode speech from noisy acoustic inputs is unknown. We show that the brain recognizes speech by integrating bottom-up acoustic signals with top-down predictions. Subjects listened to intelligible normal and unintelligible fine structure speech that lacked the predictability of the temporal envelope and did not enable access to higher linguistic representations. Their top-down predictions were manipulated using priming. Activation for unintelligible fine structure speech was confined to primary auditory cortices, but propagated into posterior middle temporal areas when fine structure speech was made intelligible by top-down predictions. By contrast, normal speech engaged posterior middle temporal areas irrespective of subjects' predictions. Critically, when speech violated subjects' expectations, activation increases in anterior temporal gyri/sulci signalled a prediction error and the need for new semantic integration. In line with predictive coding, our findings compellingly demonstrate that top-down predictions determine whether and how the brain translates bottom-up acoustic inputs into intelligible speech. PMID- 26363345 TI - Changes in functional connectivity dynamics associated with vigilance network in taxi drivers. AB - An increasing number of neuroimaging studies have suggested that the fluctuations of low-frequency resting-state functional connectivity (FC) are not noise but are instead linked to the shift between distinct cognitive states. However, there is very limited knowledge about whether and how the fluctuations of FC at rest are influenced by long-term training and experience. Here, we investigated how the dynamics of resting-state FC are linked to driving behavior by comparing 20 licensed taxi drivers with 20 healthy non-drivers using a sliding window approach. We found that the driving experience could be effectively decoded with 90% (p<0.001) accuracy by the amplitude of low-frequency fluctuations in some specific connections, based on a multivariate pattern analysis technique. Interestingly, the majority of these connections fell within a set of distributed regions named "the vigilance network". Moreover, the decreased amplitude of the FC fluctuations within the vigilance network in the drivers was negatively correlated with the number of years that they had driven a taxi. Furthermore, temporally quasi-stable functional connectivity segmentation revealed significant differences between the drivers and non-drivers in the dwell time of specific vigilance-related transient brain states, although the brain's repertoire of functional states was preserved. Overall, these results suggested a significant link between the changes in the time-dependent aspects of resting-state FC within the vigilance network and long-term driving experiences. The results not only improve our understanding of how the brain supports driving behavior but also shed new light on the relationship between the dynamics of functional brain networks and individual behaviors. PMID- 26363346 TI - Neuromagnetic evidence for hippocampal modulation of auditory processing. AB - The hippocampus is well known to be involved in memory, as well as in perceptual processing. To date, the electrophysiological process by which unilateral hippocampal lesions, such as hippocampal sclerosis (HS), modulate the auditory processing remains unknown. Auditory-evoked magnetic fields (AEFs) are valuable for evaluating auditory functions, because M100, a major component of AEFs, originates from auditory areas. Therefore, AEFs of mesial temporal lobe epilepsy (mTLE, n=17) with unilateral HS were compared with those of healthy (HC, n=17) and disease controls (n=9), thereby determining whether AEFs were indicative of hippocampal influences on the auditory processing. Monaural tone-burst stimuli were presented for each side, followed by analysis of M100 and a previously less characterized exogenous component (M400: 300-500ms). The frequency of acceptable M100 dipoles was significantly decreased in the HS side. Beam-forming-based source localization analysis also showed decreased activity of the auditory area, which corresponded to the inadequately estimated dipoles. M400 was found to be related to the medial temporal structure on the HS side. Volumetric analysis was also performed, focusing on the auditory-related areas (planum temporale, Heschl's gyrus, and superior temporal gyrus), as well as the hippocampus. M100 amplitudes positively correlated with hippocampal and planum temporale volumes in the HC group, whereas they negatively correlated with Heschl's gyrus volume in the mTLE group. Interestingly, significantly enhanced M400 component was observed in the HS side of the mTLE patients. In addition, the M400 component positively correlated with Heschl's gyrus volume and tended to positively correlate with disease duration. M400 was markedly diminished after hippocampal resection. Although volumetric analysis showed decreased hippocampal volume in the HS side, the planum temporale and Heschl's gyrus, the two major sources of M100, were preserved. These results suggested that HS significantly influenced AEFs. Therefore, we concluded that the hippocampus modulates auditory processing differently under normal conditions and in HS. PMID- 26363347 TI - Frequency-dependent spatiotemporal profiles of visual responses recorded with subdural ECoG electrodes in awake monkeys: Differences between high- and low frequency activity. AB - Electrocorticography (ECoG) constitutes a powerful and promising neural recording modality in humans and animals. ECoG signals are often decomposed into several frequency bands, among which the so-called high-gamma band (80-250Hz) has been proposed to reflect local cortical functions near the cortical surface below the ECoG electrodes. It is typically assumed that the lower the frequency bands, the lower the spatial resolution of the signals; thus, there is not much to gain by analyzing the event-related changes of the ECoG signals in the lower-frequency bands. However, differences across frequency bands have not been systematically investigated. To address this issue, we recorded ECoG activity from two awake monkeys performing a retinotopic mapping task. We characterized the spatiotemporal profiles of the visual responses in the time-frequency domain. We defined the preferred spatial position, receptive field (RF), and response latencies of band-limited power (BLP) (i.e., alpha [3.9-11.7Hz], beta [15.6 23.4Hz], low [30-80Hz] and high [80-250Hz] gamma) for each electrode and compared them across bands and time-domain visual evoked potentials (VEPs). At the population level, we found that the spatial preferences were comparable across bands and VEPs. The high-gamma power showed a smaller RF than the other bands and VEPs. The response latencies for the alpha band were always longer than the latencies for the other bands and fastest in VEPs. Comparing the response profiles in both space and time for each cortical region (V1, V4+, and TEO/TE) revealed regional idiosyncrasies. Although the latencies of visual responses in the beta, low-, and high-gamma bands were almost identical in V1 and V4+, beta and low-gamma BLP occurred about 17ms earlier than high-gamma power in TEO/TE. Furthermore, TEO/TE exhibited a unique pattern in the spatial response profile: the alpha and high-gamma responses tended to prefer the foveal regions, whereas the beta and low-gamma responses preferred the peripheral visual fields with larger RFs. This suggests that neurons in TEO/TE first receive less selective spatial information via beta and low-gamma BLP but later receive more fine-tuned spatial foveal information via high-gamma power. This result is consistent with a hypothesis previously proposed by Nakamura et al. (1993) that states that visual processing in TEO/TE starts with coarse-grained information, which primes subsequent fine-grained information. Collectively, our results demonstrate that ECoG can be a potent tool for investigating the nature of the neural computations in each cortical region that cannot be fully understood by measuring only the spiking activity, through the incorporation of the knowledge of the spatiotemporal characteristics across all frequency bands. PMID- 26363348 TI - Time-varying effective connectivity of the cortical neuroelectric activity associated with behavioural microsleeps. AB - An episode of complete failure to respond during an attentive task accompanied by behavioural signs of sleep is called a behavioural microsleep. We proposed a combination of high-resolution EEG and an advanced method for time-varying effective connectivity estimation for reconstructing the temporal evolution of the causal relations between cortical regions when microsleeps occur during a continuous visuomotor task. We found connectivity patterns involving left-right frontal, left-right parietal, and left-frontal/right-parietal connections commencing in the interval [-500; -250] ms prior to the onset of microsleeps and disappearing at the end of the microsleeps. Our results from global graph indices derived from effective connectivity analysis have revealed EEG-based biomarkers of all stages of microsleeps (preceding, onset, pre-recovery, recovery). In particular, this raises the possibility of being able to predict microsleeps in real-world tasks and initiate a 'wake-up' intervention to avert the microsleeps and, hence, prevent injurious and even multi-fatality accidents. PMID- 26363349 TI - More bilateral, more anterior: Alterations of brain organization in the large scale structural network in Chinese dyslexia. AB - Abnormalities in large-scale brain networks have been recently reported in dyslexia; however, it remains unclear whether these abnormalities are congenital (due to dyslexia per se) or arise later in development. Here, structural magnetic resonance imaging data of 17 Chinese reading disabled (RD) and 17 age-matched typically developing (TD) children were used to construct cortical thickness (sensitive to postnatal development) and surface area (sensitive to prenatal development) networks. In the thickness network, compared to TD, RD showed reduced nodal network properties (e.g., degree and betweenness) in the left hemisphere along with enhanced nodal properties mainly in the right hemisphere. As for the surface area network, compared to TD, RD demonstrated lower nodal properties in the posterior brain regions and higher nodal properties in the anterior brain regions. Furthermore, hubs in both the thickness and surface area networks in RD were more distributed in frontal areas and less distributed in parietal areas, whereas TD showed the opposite pattern. Altogether, these findings indicate that the aberrant structural connectivity in the dyslexic individuals was not only due to a late developmental effect reflected in the altered thickness network, but may also be a congenital effect during prenatal development, reflected in the altered surface network. PMID- 26363350 TI - Arterial impulse model for the BOLD response to brief neural activation. AB - The blood oxygen level dependent (BOLD) signal evoked by brief neural stimulation, the hemodynamic response function (HRF), is a critical feature of neurovascular coupling. The HRF is directly related to local transient changes in oxygen supplied by cerebral blood flow (CBF) and oxygen demand, the cerebral metabolic rate of oxygen (CMRO2). Previous efforts to explain the HRF have relied upon the hypothesis that CBF produces a non-linear venous dilation within the cortical parenchyma. Instead, the observed dynamics correspond to prompt arterial dilation without venous volume change. This work develops an alternative biomechanical model for the BOLD response based on the hypothesis that prompt upstream dilation creates an arterial flow impulse amenable to linear description. This flow model is coupled to a continuum description of oxygen transport. Measurements using high-resolution fMRI demonstrate the efficacy of the model. The model predicts substantial spatial variations of the oxygen saturation along the length of capillaries and veins, and fits the varied gamut of measured HRFs by the combined effects of corresponding CBF and CMRO2 responses. Three interesting relationships among the hemodynamic parameters are predicted. First, there is an offset linear correlation with approximately unity slope between CBF and CMRO2 responses. Second, the HRF undershoot is strongly correlated to the corresponding CBF undershoot. Third, late-time-CMRO2 response can contribute to a slow recovery to baseline, lengthening the HRF undershoot. The model provides a powerful mathematical framework to understand the dynamics of neurovascular and neurometabolic responses that form the BOLD HRF. PMID- 26363351 TI - Caenorhabditis elegans DAF-16/FOXO transcription factor and its mammalian homologs associate with age-related disease. AB - The insulin/IGF-1 signaling pathway is evolutionarily conserved and its function is mediated largely by FOXO transcription factors. Reduced insulin/IGF-1 signaling leads to translocation of FOXO proteins from the cytoplasm to the nucleus where they activate a set of genes that mediate oxidative stress, heat shock, and xenobiotic responses, innate immunity, metabolism, and autophagy. Disruptions in the insulin/IGF-1 signaling pathway affect lifespan in many species. Over the past two decades, the function of these FOXO proteins in age related diseases has been extensively studied, in the model organism Caenorhabditis elegans as well as in humans. In this review we investigate the mechanisms by which FOXO proteins influence the development of age-related disease pathways in both species. PMID- 26363353 TI - Parotid Gland Swelling Leading to Human Immunodeficiency Virus Infection Diagnosis. PMID- 26363352 TI - Automatically finding relevant citations for clinical guideline development. AB - OBJECTIVE: Literature database search is a crucial step in the development of clinical practice guidelines and systematic reviews. In the age of information technology, the process of literature search is still conducted manually, therefore it is costly, slow and subject to human errors. In this research, we sought to improve the traditional search approach using innovative query expansion and citation ranking approaches. METHODS: We developed a citation retrieval system composed of query expansion and citation ranking methods. The methods are unsupervised and easily integrated over the PubMed search engine. To validate the system, we developed a gold standard consisting of citations that were systematically searched and screened to support the development of cardiovascular clinical practice guidelines. The expansion and ranking methods were evaluated separately and compared with baseline approaches. RESULTS: Compared with the baseline PubMed expansion, the query expansion algorithm improved recall (80.2% vs. 51.5%) with small loss on precision (0.4% vs. 0.6%). The algorithm could find all citations used to support a larger number of guideline recommendations than the baseline approach (64.5% vs. 37.2%, p<0.001). In addition, the citation ranking approach performed better than PubMed's "most recent" ranking (average precision +6.5%, recall@k +21.1%, p<0.001), PubMed's rank by "relevance" (average precision +6.1%, recall@k +14.8%, p<0.001), and the machine learning classifier that identifies scientifically sound studies from MEDLINE citations (average precision +4.9%, recall@k +4.2%, p<0.001). CONCLUSIONS: Our unsupervised query expansion and ranking techniques are more flexible and effective than PubMed's default search engine behavior and the machine learning classifier. Automated citation finding is promising to augment the traditional literature search. PMID- 26363354 TI - Adrenal Crisis: Still a Deadly Event in the 21st Century. AB - Adrenal crisis is a life-threatening medical emergency, associated with a high mortality unless it is appropriately recognized and early treatment is rendered. Despite it being a treatable condition for almost 70 years, failure of adequate preventive measures or delayed treatment has often led to unnecessary deaths. Gastrointestinal illness is the most common precipitant for an adrenal crisis. Although most patients are educated about "sick day rules," patients, and physicians too, are often reluctant to increase their glucocorticoid doses or switch to parenteral injections, and thereby fail to avert the rapid deterioration of the patients' condition. Therefore, more can be done to prevent an adrenal crisis, as well as to ensure that adequate acute medical care is instituted after a crisis has occurred. There is generally a paucity of studies on adrenal crisis. Hence, we will review the current literature, while also focusing on the incidence, presentation, treatment, prevention strategies, and latest recommendations in terms of steroid dosing in stress situations. PMID- 26363355 TI - Retail Clinics: A Shift From Episodic Acute Care to Partners in Coordinated Care. PMID- 26363356 TI - The effects of advertisements that sexually objectify women on state body dissatisfaction and judgments of women: The moderating roles of gender and internalization. AB - Experimental studies have demonstrated that exposure to idealized images of women increases state body image disturbance. However, little work has experimentally examined the effects of exposure to images that sexually objectify women, especially as it relates to women and men's state body dissatisfaction and judgments of women. In the current study, 437 women and men were randomly assigned to view advertisements that sexually objectify women and portray appearance ideals, or to view non-appearance-related advertisements. Results indicated that state body dissatisfaction increased for women and men exposed to advertisements that sexually objectified women, although this effect was larger for women. Trait internalization of appearance ideals moderated this effect, indicating that women and men with higher internalization exhibited greater state body dissatisfaction after viewing women sexually objectified in advertisements. Exposure to women sexually objectified in advertisements did not affect women's or men's attractiveness or competence ratings of women in university advertisements. PMID- 26363357 TI - Body image and appearance perceptions from immigrant adolescents in Canada: An interpretive description. AB - Body dissatisfaction has been linked to a number of poor health outcomes, including eating disorders. However, very few studies have investigated body dissatisfaction among immigrant adolescents. Using inductive qualitative inquiry, this study recruited a purposeful sample of immigrant adolescents (N=18, 78% female) with an eating disorder (n=8) and without an eating disorder (n=10). All adolescents were between 16 and 19 years of age (M=16.80, SD=0.89) and were recruited from three municipalities in Ontario. Each adolescent participated in a face-to-face, qualitative interview. Content analysis revealed descriptions of body image that were similar across the sample. The main themes emerging from this work include (a) the "moderately slim" and "moderately muscular" ideal, (b) the "slim and curvy paradox," (c) "ideal" privilege, (d) having an "expected" appearance, and (e) wishful comparisons. Findings have implications for reducing appearance-related dissatisfaction among immigrant adolescents in Canada. PMID- 26363358 TI - Both the Jasmonic Acid and the Salicylic Acid Pathways Contribute to Resistance to the Biotrophic Clubroot Agent Plasmodiophora brassicae in Arabidopsis. AB - The role of salicylic acid (SA) and jasmonic acid (JA) signaling in resistance to root pathogens has been poorly documented. We assessed the contribution of SA and JA to basal and partial resistance of Arabidopsis to the biotrophic clubroot agent Plasmodiophora brassicae. SA and JA levels as well as the expression of the SA-responsive genes PR2 and PR5 and the JA-responsive genes ARGAH2 and THI2.1 were monitored in infected roots of the accessions Col-0 (susceptible) and Bur-0 (partially resistant). SA signaling was activated in Bur-0 but not in Col-0. The JA pathway was weakly activated in Bur-0 but was strongly induced in Col-0. The contribution of both pathways to clubroot resistance was then assessed using exogenous phytohormone application and mutants affected in SA or JA signaling. Exogenous SA treatment decreased clubroot symptoms in the two Arabidopsis accessions, whereas JA treatment reduced clubroot symptoms only in Col-0. The cpr5-2 mutant, in which SA responses are constitutively induced, was more resistant to clubroot than the corresponding wild type, and the JA signaling deficient mutant jar1 was more susceptible. Finally, we showed that the JA mediated induction of NATA1 drove N(delta)-acetylornithine biosynthesis in infected Col-0 roots. The 35S::NATA1 and nata1 lines displayed reduced or enhanced clubroot symptoms, respectively, thus suggesting that in Col-0 this pathway was involved in the JA-mediated basal clubroot resistance. Overall, our data support the idea that, depending on the Arabidopsis accession, both SA and JA signaling can play a role in partial inhibition of clubroot development in compatible interactions with P. brassicae. PMID- 26363359 TI - Engineering a Platform for Photosynthetic Pigment, Hormone and Cembrane-Related Diterpenoid Production in Nicotiana tabacum. AB - Plants synthesize a large number of isoprenoids that are of nutritional, medicinal and industrial importance. 1-Deoxy-d-xylulose 5-phosphate reductoisomerase (DXR) catalyzes the first committed step for plastidial isoprenoid biosynthesis. Here, we identified two DXR isogenes, designated NtDXR1 and NtDXR2, from tetraploid common tobacco (Nicotiana tabacum L.). Southern blotting and genotyping analysis revealed that two NtDXR genes existed in the tetraploid tobacco genome; NtDXR1 and NtDXR2 were separately derived from N. tomentosiformis and N. sylvestris. Both NtDXRs were localized in chloroplasts. Expression patterns indicated that NtDXR1 and NtDXR2 had similar expression profiles. NtDXR genes were highly expressed in leaves with or without trichomes; expression was relatively reduced in flowers and stems, weak in leaf trichomes and marginal in roots and seeds. Overexpressing NtDXR1 under control of the 35S promoter resulted in longer primary roots and enhancement of various photosynthetic pigments and hormones in leaves. In contrast, there were no significant changes in cembrane-related diterpenoids synthesized in glandular trichomes. To elucidate further the function of DXR in the biosynthesis of diterpenoids, overexpression vectors for NtDXR1 under the control of a trichome specific CYP promoter were transferred to tobacco plants. CYP:NtDXR1 tobacco exhibited larger glandular cells and increased cembrane-related diterpenoids in leaf glandular trichomes. Moreover, transcripts of eight MEP (2-C-methyl-d erythritol 4-phosphate) pathway genes were significantly up-regulated in NtDXR1 overexpressing tobacco plants, indicating that overexpression of NtDXR could boost the expression of downstream genes in the MEP pathway. Our results suggested that overexpression of NtDXR1 could increase the levels of photosynthetic pigments, leaf surface exudates and hormones though the MEP pathway. PMID- 26363360 TI - The beta-catenin signaling pathway induces aggressive potential in breast cancer by up-regulating the chemokine CCL5. AB - beta-Catenin signaling plays a pivotal role in the genesis of a variety of malignant tumors, but its role in breast cancer has not been fully elucidated. Here, we examined whether deregulation of beta-catenin signaling is related to the aggressive characteristics of certain types of breast cancers. Analysis of cytokine levels in MDA-MB-231 cells overexpressing a constitutively active form of beta-catenin (CAbeta-catenin) revealed a higher level of CCL5 expression. Cells transfected with CAbeta-catenin or stimulated with recombinant CCL5 exhibited increased cell invasion activity and spheroid formation in vitro. Furthermore, CAbeta-catenin-transfected MDA-MB-231 cells formed larger tumor masses that contained more Ki-67-positive cells and infiltrating lymphocytes than did the control cells. An inhibitor of CCR5 and a pan-CXCR neutralizing antibody dramatically reduced CAbeta-catenin-promoted activities. In addition to CCL5, 6 BIO, a chemical activator of beta-catenin, induced cell invasion and spheroid formation in MDA-MB-231 cells. Furthermore, high levels of nuclear beta-catenin accumulation were detected in breast cancer in patients with metastasis but not in those without metastasis. Nuclear beta-catenin localization is related to increased CCL5 production in breast cancer. These findings suggest that beta catenin expression enhances tumor progression via chemokine production in breast cancers and that beta-catenin signaling is a critical regulator of the aggressive traits of breast cancers. PMID- 26363361 TI - Localization of 14-3-3delta/xi on the neuronal cell surface. AB - 14-3-3 proteins are intracellularly expressed as ubiquitous adaptor proteins. Here, we found localization of 14-3-3delta/xi on the neuronal cell surface. 14-3 3delta/xi was identified as a membrane target for 15-deoxy-Delta(12,14) prostaglandin J2 (15d-PGJ2). 15d-PGJ2 is a pathological mediator of neurodegenerative diseases including Alzheimer's disease (AD). A causative peptide for AD, amyloid beta, is one of binding partner of 14-3-3delta/xi. Non permeabilized neurons were used to avoid the intracellular effects of anti-14-3 3delta/xi antibody in the present study. The plasmalemmal 14-3-3delta/xi, but not the cytosolic one, was stimulated by its specific antibody, resulting in neuronal cell death. The neurotoxicity of anti-14-3-3delta/xi antibody was suppressed by an antioxidant, catalase. Catalase prevented neurons from anti-14-3-3delta/xi antibody-generating neurotoxic H2O2. The neuroprotective effect of catalase was also detected with the post-treatment of neurons after the application of anti-14 3-3delta/xi antibody. Activation of mitogen-activated protein kinase signaling cascade is a down-stream consequence of H2O2 exposure. A c-Jun N-terminal kinase inhibitor suppressed anti-14-3-3delta/xi antibody-induced neuronal cell death. To my knowledge, this is the first report that the antibody-stimulated plasmalemmal 14-3-3delta/xi induced neuronal cell death. Furthermore, H2O2 and JNK contributed to the neurotoxicity of anti-14-3-3delta/xi antibody as well as those of amyloid beta and 15d-PGJ2. PMID- 26363362 TI - United States trends in thrombolysis for older adults with acute ischemic stroke. AB - OBJECTIVE: Thrombolysis for ischemic stroke has been increasing in the United States. We sought to investigate recent trends in thrombolysis use in older adults. METHODS: A retrospective, observational analysis of hospitalization data from the Nationwide Inpatient Sample (NIS) in 2005-2010 was performed. Older adults (>=65 years) admitted with a primary diagnosis of acute ischemic stroke were included. Trends in the population-based rates of thrombolysis and outcomes from the NIS were evaluated using the Cochran-Armitage test. RESULTS: Thrombolysis in older adult stroke patients increased from 1.7% to 5.4% (2005 2010; trend P<0.001). Large increases were observed among urban patients, urban hospitals, and high volume facilities. Individuals >=85 years were less likely to receive thrombolysis than younger ages throughout the study period, although there was an increase from an odds ratio of 0.50 (95% CI: 0.44-0.57) to 0.75 (95% CI: 0.69-0.81) from 2005-2006 to 2009-2010 when compared to 65-74 year olds. For those receiving thrombolysis, no change was observed in intracerebral hemorrhage over time. In-hospital mortality rates did not change significantly over the study period for age subgroups and length of stay declined from 2005 to 2010 for the thrombolysis group (7.6 vs 7.0 days; trend P<0.001). CONCLUSIONS: Rates of thrombolysis in older adults progressively increased, especially in the oldest old. Increases were largely driven by urban and high volume hospitals. PMID- 26363363 TI - Quality of life in patients with PD and their caregiving spouses: A view from both sides. AB - OBJECTIVE: In contrast to the wealth of studies on quality of life (QoL) in patients with Parkinson's disease, the number of reports on QoL in caregivers, especially partners as primary caregivers, is fairly limited. In this report we wanted to investigate if patients and caregiving partners are able to reliably estimate each other's present and former QoL. METHODS: We used a visual analogue scale in order to obtain the patients' and their partners' scores of present and former QoL. Moreover we studied correlations of these mutual estimates with demographic variables and measures of patient dependency. RESULTS: As expected both patients and partners considered their QoL as decreased when compared to former QoL. Interestingly both patients and partners were able to reliably estimate each other's QoL. Patients judged their own former QoL and that of their partner as lower as did their partners. All QoL measures were significantly correlated to measures of mental state and patient dependency. There was a negative correlation with increasing age but not with disease duration. CONCLUSION: These results indicate the validity of using proxy information by a caregiving partner in estimations of QoL. PMID- 26363364 TI - A minimally invasive approach to defects of the pars interarticularis: Restoring function in competitive athletes. AB - OBJECTIVES: To understand that young athletes have a higher incidence of pars interarticularis defects than the general population. This may be due to an immature spine put under higher stress loads at an early age. Traditionally, surgery was reserved for those who failed conservative therapy, and consisted of open exposure, bone grafting and placement of pedicle screws. This leads to a long recovery period and limited ability to return to competitive sport. METHODS: Four collegiate and professional level athletes, three high school athletes, and one member of the National Guard presented with back pain from spondylolysis without spondylolisthesis. All underwent minimally invasive surgery (MIS) to directly repair the pars defect, for a total of sixteen pars defects repaired in eight patients. Described is an application of a MIS pars repair technique that has not previously been reported, which recreates the normal anatomy rather fusing across a motion segment. RESULTS: Five patients were discharged the day following surgery and three were discharged on postoperative day 2. Six of the patients returned to their previous level of competitiveness. Two were unable to achieve the same level of play, both of whom failed to fuse the spondylolysis. Patients all initially reported clinical improvement postoperatively and there was overall mean improvement on patient reported outcome measures (SF36 physical and mental component scores, visual analog scale, and Oswestry disability index). CONCLUSION: MIS advantages include less muscle tissue disruption and restoration of the natural anatomy. This leads to a more rapid recovery, decreased perioperative pain, minimal blood loss, earlier mobilization and decreased hospital length of stay. Overall this allows the athlete to start therapy earlier and return to competition sooner and at his/her pre-operative competitive level. The described MIS repair technique outcomes are similar to those that have been reported in the literature and have allowed a high rate of return to athletics in high performing patients; critical to their quality of life. PMID- 26363365 TI - Short-term impact of fampridine on motor and cognitive functions, mood and quality of life among multiple sclerosis patients. AB - OBJECTIVE: Previous studies have predominantly investigated the effect of fampridine on lower extremities motor functions while data on its impact on other symptoms of multiple sclerosis (MS) are scarce. The aim of our study was to assess the impact of fampridine on walking, arm/hand function, fatigue, cognitive function, mood and quality of life among responders. METHODS: Our prospective non randomized study included 30 patients with different types of MS, aged 35-70, EDSS value 3.5-6.5. They were treated with 10mg of fampridine twice daily. The examinations were performed before the treatment, after 14 days, when responders were defined by T25FW (Timed 25-Foot Walk) and 2-min walk test (2MWT) was performed, and after 28 days of treatment, when only the responders were examined. Standardized protocols and questionnaires were used to evaluate the impact of fampridine on walking speed (T25FW, 2MWT), arm/hand function (9-HPT - Nine-Hole Peg Test), cognitive function (PASAT - Paced Auditory Serial Addition Test), total MSFC score (Multiple Sclerosis Functional Composite), fatigue (MFIS Modified Fatigue Impact Scale), mood (BDI - Beck Depression Inventory) and quality of life (EQ-5D index, EQ-VAS - Euro Quality of Life - 5 Dimension questionnaire and visual analogue scale) in responders. RESULTS: Response rate was 56.7%. Average improvement of T25FW and 2MWT after 14 days of treatment in responders was 3.6s (34.5%) and 37.4m (42.3%), respectively. This improvement persisted after 28 days of treatment. In non-responders there was no significant improvement of T25FW after 14 days (p=0.689), but there was improvement of 2MWT for 13.4m (14.3%) (p=0.000). After 28 days of treatment significant improvement among responders occurred in total MSFC score (p=0.001), 9-HPT (p=0.002), BDI (p=0.005), MFIS total score (p=0.003), physical (p=0.001), cognitive (p=0.008) MFIS subscales, and EQ-5D index (p=0.012). There were implied trends towards improvement in EQ-VAS and psychosocial MFIS subscale, yet not significant (p=0.057 and p=0.127, respectively). There was no statistically significant improvement of PASAT (p=0.432). CONCLUSIONS: The results of our study highlight the potential of fampridine for improving not only walking speed but also arm/hand function, physical and cognitive fatigue, mood and quality of life. There was no objective improvement of cognitive function. Further placebo controlled studies will be needed for precise definition of fampridine's action beyond its impact on walking. PMID- 26363367 TI - Comparison of templates for homology model of rho1 GABAC receptors: More insights to the orthosteric binding site's structure and functionality. AB - Five sets of rho1 GABAC homology models were generated based on X-ray crystal structures of the acetylcholine binding protein (AChBP), the ion channel from Caenorhabditis elegans (GLIC), the ion channel from Erwinia chrysanthemi (ELIC), the homomeric GABAA beta3 ion channel, and the homomeric alpha-subunit of glutamate-gated homopentameric chloride channel (GluCl). The GluCl based model was found to the represent the structure of rho1 GABAC receptors. The GABA pose docked in the selected best model was confirmed by QM-polarized ligand docking and induced fit docking protocol, and used to study molecular interactions in the rho1 GABA binding site. The potential interactions of identified residues are discussed. This study identified several residues with potential ligand interactions located on loops F and G with their side chain oriented toward the binding site such as Ser215 and Gln83. The partial agonists muscimol and imidazole-4-acetic acid (I4AA) were docked into the binding site of the most reliable 'GABA bound' homology model. The potency and efficacy of these partial agonists in activating recombinant rho1 receptors were correlated with their docking results. The model predicts that muscimol resembles GABA in the docking pose with similar interactions. However, I4AA has a very different docking pose to GABA and was predicted by the model to form pi-pi stacking with aromatic residues in the orthosteric binding site. A set of TPMPA bound rho1 homology models based on the GluClalpha 'apo state' template was built in order to study a competitive antagonist in the rho1 orthosteric binding site. The results demonstrated the ability of our model to explain most experimental findings and predict potential roles of residues within the orthosteric binding site. PMID- 26363368 TI - Atopic dermatitis is associated with Caesarean sections in Korean adolescents, but asthma is not. AB - AIM: Studies on the associations between mode of delivery and allergic diseases have produced different results, and research has rarely been conducted in Asian countries such as South Korea. This study assessed the relationship between mode of delivery and atopic dermatitis and asthma in Korean adolescents. METHODS: Data collected from the Korea National Health and Nutrition Examination Survey between 2010 and 2011 were used. We included 1302 adolescents aged from 12 to 18 years, and multivariable logistic regression analysis was performed. RESULTS: The odds ratio (OR) of having atopic dermatitis in adolescents born by Caesarean section compared with vaginal delivery was 1.50, with a 95% confidence interval (95% CI) of 1.01-2.22, after adjusting for age and sex. The association remained significant after further adjustments for body mass index, breastfeeding and serum 25-hydroxyvitamin D level (OR = 1.61, 95% CI = 1.05-2.47) and when fat intake was added to those variables (OR = 1.80, 95% CI = 1.14-2.85). However, asthma was not associated with mode of delivery in any of the models. CONCLUSIONS: Atopic dermatitis in adolescents was associated with Caesarean delivery, which is common in South Korea. The findings suggest that the frequency of this practice should be reconsidered and that further research with longitudinal evaluation of relevant mechanisms is needed. PMID- 26363369 TI - Evaluation of a rapid method for the simultaneous quantification of ribavirin, sofosbuvir and its metabolite in rat plasma by UPLC-MS/MS. AB - A rapid and sensitive ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for the determination of ribavirin, sofosbuvir and its metabolite GS-331007 in rat plasma was established. The analytes and the internal standard (midazolam) were separated on an Acquity UPLC BEH C18 chromatography column (2.1mm*50mm, 1.7MUm) using gradient elution with a mobile phase of acetonitrile and 0.1% formic acid in water at a flow rate of 0.4mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) mode to monitor the precursor-to-product ion transitions of m/z 245.1->113.1 for ribavirin, m/z 530.3->243.1 for sofosbuvir, m/z 261.5->113.1 for GS-331007 and m/z 326.2->291.1 for midazolam (IS) using a positive electrospray ionization interface. The method was validated over a concentration range of 5-1000ng/mL for ribavirin, 10-2000ng/mL for sofosbuvir and 10-2000ng/mL for GS-331007. Total time for each chromatograph was 3.0min. The intra- and inter-day precision and accuracy of the quality control samples at low, medium, and high concentration levels exhibited relative standard deviations (RSD) <10.0% and the accuracy values ranged from -10.6% to 11.6%. The method was successfully applied to a pharmacokinetic study of ribavirin, sofosbuvir and GS 331007 in rats. PMID- 26363366 TI - IL-21-driven neoplasms in SJL mice mimic some key features of human angioimmunoblastic T-cell lymphoma. AB - SJL/J mice exhibit a high incidence of mature B-cell lymphomas that require CD4(+) T cells for their development. We found that their spleens and lymph nodes contained increased numbers of germinal centers and T follicular helper (TFH) cells. Microarray analyses revealed high levels of transcripts encoding IL-21 associated with high levels of serum IL-21. We developed IL-21 receptor (IL21R) deficient Swiss Jim Lambart (SJL) mice to determine the role of IL-21 in disease. These mice had reduced numbers of TFH cells, lower serum levels of IL-21, and few germinal center B cells, and they did not develop B-cell tumors, suggesting IL-21 dependent B-cell lymphomagenesis. We also noted a series of features common to SJL disease and human angioimmunoblastic T-cell lymphoma (AITL), a malignancy of TFH cells. Gene expression analyses of AITL showed that essentially all cases expressed elevated levels of transcripts for IL21, IL21R, and a series of genes associated with TFH cell development and function. These results identify a mouse model with features of AITL and suggest that patients with the disease might benefit from therapeutic interventions that interrupt IL-21 signaling. PMID- 26363370 TI - Simultaneous determination of macitentan and its active metabolite in human plasma by liquid chromatography-tandem mass spectrometry. AB - Macitentan is a newly approved endothelin receptor antagonist (ERA) for the long term treatment of PAH with superior receptor-binding properties and a longer duration of action compared to other available ERAs. However, analytical methods for simultaneous determination of macitentan and its active metabolite, ACT 132577, in human plasma have not been fully reported in the literature. In this work, a fast, sensitive, and reliable high-performance liquid chromatography tandem mass spectrometry method (HPLC-MS/MS) was firstly developed and completely validated for simultaneous determination of macitentan and its active metabolite in human plasma. Plasma samples were processed with a protein precipitation using acetonitrile, followed by chromatographic separation using an Inertsil ODS-SP column (100*2.1mm, 3.5MUm) under isocratic elution with a mobile phase consisting of acetonitrile and 0.2% formic acid at a flow rate of 0.3mL/min. Quantification was operated in multiple reaction monitoring (MRM) mode using the transitions m/z 547.1->201.0 for macitentan, m/z 589.0->203.0 for ACT-132577, and m/z 380.5 >243.3 for the IS (donepezil). The assay exhibited a linear range of 1-500ng/mL for both macitentan and ACT-132577. The accuracy and the intra- and inter precisions were within acceptable ranges and no significant matrix effect was observed during the method validation. The developed method was successfully utilized to a human pharmacokinetic study of macitentan as well as ACT-132577 after oral administration of 10mg macitentan tablet in healthy Chinese volunteers. PMID- 26363371 TI - Vacuum-powered bubble-assisted solvent extraction followed by macroporous resin enrichment for isolation of podophyllotoxin from Sinopodophyllum emodi. AB - A vacuum-powered bubble-assisted solvent extraction (VBE) technique was used to extract podophyllotoxin from the root of Sinopodophyllum emodi. We optimized the VBE procedure and showed it had the highest efficiency of extraction compared to other conventional extraction techniques. Based upon the results of single-factor experiments, a three-factor, three-level experiment design was developed by application of a Box-Behnken design. The method was validated by stability, repeatability and recovery experiments. The optimal conditions were: solvent, 60% (v/v) ethanol; particle size of the sample, 60-80 mesh; soak time, 2h; liquid/solid ratio, 21L/kg; air flow, 32mL/min; vacuum-powered bubble extraction time, 65min. The VBE method we developed achieved efficient extraction of podophyllotoxin from S. emodi. The podophyllotoxin extracted can be enriched and separated by an HPD300 macroporous resin adsorption and desorption process. The results indicated that VBE is a convenient, rapid and efficient sample preparation technique. PMID- 26363372 TI - Preparative isolation, quantification and antioxidant activity of dihydrochalcones from Sweet Tea (Lithocarpus polystachyus Rehd.). AB - Dihydrochalcones are the main active components of Lithocarpus polystachyus Rehd. (Sweet Tea), they are directly related to the sweet tonic beverage and traditional herb. In this work, two runs of preparative high-speed counter current chromatography (HSCCC) with a two-phase solvent system composed of n hexane/ethyl acetate/ethanol/water (1:4:3:4, v/v) were employed to separate three dihydrochalcones (phloridzin, trilobatin and phloretin) from Sweet Tea. About 6.4mg of phloridzin, 48.4mg of trilobatin, and 4.7mg of phloretin with purities of 96.7%, 98.4% and 98.1% were obtained from 130mg of the crude Sweet Tea extract. Phloridzin, trilobatin, and phloretin had effective radical scavenging activities, with IC50 values of 866.80, 20.16 and 179.47MUg/mL, respectively, in a 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical method. The contents of phloridzin, trilobatin and phloretin in dried old leaves and tender leaves of tea were in the range of 10.1-18.0, 113.7-128.8, 3.6-4.3mg/g and 9.3-9.8, 82.9-103.1, 1.9-2.5mg/g, respectively. The results indicated that the HPLC had good precision, accuracy and repeatability for the determination of three dihydrochalcones in samples. PMID- 26363373 TI - A rapid and simple method for the simultaneous determination of four endogenous monoamine neurotransmitters in rat brain using hydrophilic interaction liquid chromatography coupled with atmospheric-pressure chemical ionization tandem mass spectrometry. AB - Endogenous monoamine neurotransmitters play an essential role in neural communication in mammalians. Many quantitative methods for endogenous monoamines have been developed during recent decades. Yet, matrix effect was usually a challenge in the quantification, in many cases asking for tedious sample preparation or sacrificing sensitivity. In this work, a simple, fast and sensitive method with no matrix effect was developed to simultaneously determine four endogenous monoamines including serotonin, dopamine, epinephrine and norepinephrine in rat brain tissues, using hydrophilic interaction liquid chromatography coupled with atmospheric-pressure chemical ionization tandem mass spectrometry. Various conditions, including columns, chromatographic conditions, ion source, MS/MS conditions, and brain tissue preparation methods, were optimized and validated. Pre-weighed 20mg brain sample could be effectively and reproducibly homogenized and protein-precipitated by 20 times value of 0.2% formic acid in cold organic solvents (methanol-acetonitrile, 10:90, v/v). This method exhibited excellent linearity for all analytes (regression coefficients>0.998 or 0.999). The precision, expressed as coefficients of variation, was less than 3.43% for intra-day analyses and ranged from 4.17% to 15.5% for inter-day analyses. Good performance was showed in limit of detection (between 0.3nM and 3.0nM for all analytes), recovery (90.8-120%), matrix effect (84.4-107%), accuracy (89.8-100%) and stability (88.3-104%). The validated method was well applied to simultaneously determine the endogenous serotonin, dopamine, epinephrine and norepinephrine in four brain sections of 18 Wistar rats. The quantification of four endogenous monoamines in rat brain performed excellently in the sensitivity, high throughput, simple sample preparation and matrix effect. PMID- 26363374 TI - Electrospun nanostructured polystyrene as a new coating material for solid-phase microextraction: Application to separation of multipesticides from honey samples. AB - For the first time, electrospun polystyrene nanostructure was used as coating material on a stainless steel wire for solid-phase microextraction. Surface morphology of the coating was studied by scanning electron microscopy which showed the formation of nanofibers on the wire. The coating was stable after conditioning at 250 degrees C for 2h. The efficiency of the polystyrene coating was approved by extracting a mixture of seven pesticides (polar and apolar) from head space of honey samples followed by gas chromatography-mass spectrometry. The important parameters affecting extraction efficiency such as, extraction time and temperature, desorption conditions, agitation rate and ionic strength were investigated. Under optimized experimental conditions, detection limits for the investigated pesticides ranged from 0.1-2MUgL(-1). The intra- and inter-day precisions of the developed method were 3.5-17.6% and 10.0-25.0%, respectively. Finally, all the investigated pesticides were spiked to honey samples and extracted by the proposed method. The accuracies of determination of all the species were found to be in the range of 81-125%. PMID- 26363375 TI - Agent-based modeling of porous scaffold degradation and vascularization: Optimal scaffold design based on architecture and degradation dynamics. AB - A multi-layer agent-based model (ABM) of biomaterial scaffold vascularization is extended to consider the effects of scaffold degradation kinetics on blood vessel formation. A degradation model describing the bulk disintegration of porous hydrogels is incorporated into the ABM. The combined degradation-angiogenesis model is used to investigate growing blood vessel networks in the presence of a degradable scaffold structure. Simulation results indicate that higher porosity, larger mean pore size, and rapid degradation allow faster vascularization when not considering the structural support of the scaffold. However, premature loss of structural support results in failure for the material. A strategy using multi layer scaffold with different degradation rates in each layer was investigated as a way to address this issue. Vascularization was improved with the multi-layered scaffold model compared to the single-layer model. The ABM developed provides insight into the characteristics that influence the selection of optimal geometric parameters and degradation behavior of scaffolds, and enables easy refinement of the model as new knowledge about the underlying biological phenomena becomes available. STATEMENT OF SIGNIFICANCE: This paper proposes a multi-layer agent-based model (ABM) of biomaterial scaffold vascularization integrated with a structural-kinetic model describing bulk degradation of porous hydrogels to consider the effects of scaffold degradation kinetics on blood vessel formation. This enables the assessment of scaffold characteristics and in particular the disintegration characteristics of the scaffold on angiogenesis. Simulation results indicate that higher porosity, larger mean pore size, and rapid degradation allow faster vascularization when not considering the structural support of the scaffold. However, premature loss of structural support by scaffold disintegration results in failure of the material and disruption of angiogenesis. A strategy using multi-layer scaffold with different degradation rates in each layer was investigated as away to address this issue. Vascularization was improved with the multi-layered scaffold model compared to the single-layer model. The ABM developed provides insight into the characteristics that influence the selection of optimal geometric and degradation characteristics of tissue engineering scaffolds. PMID- 26363377 TI - Correlating cell transfectability and motility on materials with different physico-chemical properties. AB - Gene delivery into cells can be facilitated by adding plasmid DNA/transfection reagent complexes in culture medium or pre-adsorbing the complexes on the substrate before cell seeding. Using transfection reagents, however, often causes cytotoxicity. Effective delivery of naked plasmid without any transfection reagent remains a challenge. In this study, we cultured human umbilical cord derived mesenchymal stem cells (hMSCs) on different biomaterial substrates with different physico-chemical properties and examined the transfectability of naked plasmid. Specifically, we synthesized a negatively charged polyurethane (PU) to mimic the hyaluronan-modified chitosan (CS-HA) membranes previously found to promote the transfection of naked plasmid. We observed that the PU membranes were as effective as CS-HA membranes in substrate-mediated delivery of naked plasmid into hMSCs. PU membranes with surface microgrooves further increased the gene delivery efficiency to a similar level as the commercial transfection reagent but without the harmful effect. The gene delivery efficiency was associated with the extent of activation of cellular integrins beta1 and alpha5 on different substrates. Moreover, the delivery efficiency was positively correlated with the cell migration rate on various substrates. The substrate-mediated gene delivery by synthetic polymeric substrates supports that integrin activation and cell behavior (e.g. migration and transfectability) changes can be modulated by synthetic polymer surface with microfeatures. The transfection by PU microgrooves is easy, nontoxic, and as effective as the commercial transfection reagent. PMID- 26363376 TI - Biological thiols-triggered hydrogen sulfide releasing microfibers for tissue engineering applications. AB - By electrospinning of polycaprolactone (PCL) solutions containing N (benzoylthio)benzamide (NSHD1), a H2S donor, fibrous scaffolds with hydrogen sulfide (H2S) releasing capability (H2S-fibers) are fabricated. The resultant microfibers are capable of releasing H2S upon immersion in aqueous solution containing biological thiols under physiological conditions. The H2S release peaks of H2S-fibers appeared at 2-4h, while the peak of donor alone showed at 45 min. H2S release half-lives of H2S-fibers were 10-20 times longer than that of donor alone. Furthermore, H2S-fibers can protect cells from H2O2 induced oxidative damage by significantly decreasing the production of intracellular reactive oxygen species (ROS). Finally, we investigated the H2S-fibers application as a wound dressing in vitro. Given that H2S has a broad range of physiological functions, H2S-fibers hold great potential for various biomedical applications. STATEMENT OF SIGNIFICANCE: Hydrogen sulfide, as a gaseous messenger, plays a crucial role in many physiological and pathological conditions. Recent studies about functions of H2S suggests H2S-based therapy could be promising therapeutic strategy for many diseases, such as cardiovascular disease, arthritis, and inflammatory bowel disease. Although many H2S donors have been developed and applied for biomedical studies, most of H2S donors have the shortage that the H2S release is either too fast or uncontrollable, which poorly mimic the biological generation of H2S. By simply combining electrospinning technique with our designed biological thiols activated H2S donor, NSHD1, we fabricated H2S releasing microfibers (H2S-fibers). This H2S-fibers significantly prolonged the releasing time compared to H2S donor alone. By adjusting the electrospinning parameters, tunable releasing profiles can be achieved. Moreover, the H2S fibers can protect cardiac myoblasts H9c2 and fibroblast NIH 3T3 from oxidative damage and support their proliferation as cellular scaffolds. To our knowledge, this is the first report of electrospun fibers with H2S releasing capacity. We anticipate this H2S-releasing scaffold will have great potential for biomedical applications. PMID- 26363378 TI - Highly selective BSA imprinted polyacrylamide hydrogels facilitated by a metal coding MIP approach. AB - We report the fabrication of metal-coded molecularly imprinted polymers (MIPs) using hydrogel-based protein imprinting techniques. A Co(II) complex was prepared using (E)-2-((2 hydrazide-(4-vinylbenzyl)hydrazono)methyl)phenol; along with iron(III) chloroprotoporphyrin (Hemin), vinylferrocene (VFc), zinc(II) protoporphyrin (ZnPP) and protoporphyrin (PP), these complexes were introduced into the MIPs as co-monomers for metal-coding of non-metalloprotein imprints. Results indicate a 66% enhancement for bovine serum albumin (BSA) protein binding capacities (Q, mg/g) via metal-ion/ligand exchange properties within the metal coded MIPs. Specifically, Co(II)-complex-based MIPs exhibited 92 +/- 1% specific binding with Q values of 5.7 +/- 0.45 mg BSA/g polymer and imprinting factors (IF) of 14.8 +/- 1.9 (MIP/non-imprinted (NIP) control). The selectivity of our Co(II)-coded BSA MIPs were also tested using bovine haemoglobin (BHb), lysozyme (Lyz), and trypsin (Tryp). By evaluating imprinting factors (K), each of the latter proteins was found to have lower affinities in comparison to cognate BSA template. The hydrogels were further characterised by thermal analysis and differential scanning calorimetry (DSC) to assess optimum polymer composition. STATEMENT OF SIGNIFICANCE: The development of hydrogel-based molecularly imprinted polymer (HydroMIPs) technology for the memory imprinting of proteins and for protein biosensor development presents many possibilities, including uses in bio-sample clean-up or selective extraction, replacement of biological antibodies in immunoassays and biosensors for medicine and the environment. Biosensors for proteins and viruses are currently expensive to develop because they require the use of expensive antibodies. Because of their biomimicry capabilities (and their potential to act as synthetic antibodies), HydroMIPs potentially offer a route to the development of new low-cost biosensors. Herein, a metal ion-mediated imprinting approach was employed to metal-code our hydrogel based MIPs for the selective recognition of bovine serum albumin (BSA). Specifically, Co(II)-complex based MIPs exhibited a 66% enhancement (in comparison to our normal MIPs) exhibiting 92 +/- 1% specific binding with Q values of 5.7 +/- 0.45 mg BSA/g polymer and imprinting factors (IF) of 14.8 +/- 1.9 (MIP/ non-imprinted (NIP) control). The proposed metal-coded MIPs for protein recognition are intended to lead to unprecedented improvement in MIP selectivity and for future biosensor development that rely on an electrochemical redox processes. PMID- 26363379 TI - Evolutionary conservation and function of the human embryonic stem cell specific miR-302/367 cluster. AB - miRNA clusters define a group of related miRNAs closely localized in the genome with an evolution that remains poorly understood. The miR-302/367 cluster represents a single polycistronic transcript that produces five precursor miRNAs. The cluster is highly expressed and essential for maintenance of human embryonic stem cells. We found the cluster to be highly conserved and present in most mammals. In primates, seed sequence and miRNA structure are conserved, but inter precursor sequences are evolving. Insertions of new miRNAs, deletions of individual miRNAs, and a cluster duplication observed in different species suggest an actively evolving cluster. Core transcriptional machinery consisting of NANOG and OCT-4 transcription factors that define stem cells are present upstream of the miR-302/367 cluster. Interestingly, we found the miR-302/367 cluster flanking region to be enriched as a target site of other miRNAs suggesting a mechanism for feedback control. Analysis of miR-302 and miR-367 targets demonstrated concordance of gene set enrichment groups at high gene ontology levels. This cluster also expresses isomiRs providing another means of establishing sequence diversity. Finally, using three different kidney tumor datasets, we observed consistent expression of miR-302 family members in normal tissue while adjacent tumor tissue showed a significant lack of expression. Clustering expression levels of miR-302 validated target genes showed a significant correlation between miR-302/367 cluster miRNAs and a subset of validated gene targets in healthy and adjacent tumor tissues. Taken together, our data show a highly conserved and still evolving miRNA cluster that may have additional unrecognized functions. PMID- 26363380 TI - Seroprevalence of mumps in an epidemic period in Medellin, Colombia. AB - OBJECTIVE: We related seroprevalence and outbreaks data in order to identify factors that could explain the occurrence of outbreaks despite high vaccination coverage in Medellin Colombia. METHODS: Samples from a population seroprevalence data obtained in 2009 in a random survey were analyzed. IgG levels were determined for mumps using 2 commercial tests of 2119 individuals aged 6-64 years. A comparative analysis was undertaken using age-specific mumps seroprevalence data and information of 98 epidemiological investigations of mumps outbreaks reported in 2009. RESULTS: Overall, seroprevalence was 91.6% (95% CI=89.3-93.5%). The age-specific seronegativity was 20.3% and 20.6% in age groups 11-15 years and 16-20 years respectively. Individuals aged 6-20 years were the most affected during outbreaks. In individuals born in 2003, a year after the change in the booster schedule from 10 to 5 years, the proportion of unvaccinated individuals (14%) and those who received only one dose of MMR (45%) increased substantially. On average, 23.5 days elapsed between the onset of symptoms in secondary cases and the outbreak investigation. CONCLUSION: Potential contributing factors for the occurrence of outbreaks of mumps were the relatively high prevalence of seronegativity among individuals aged 11-20 years, delays in investigation and control of outbreaks, and incomplete vaccination schedules. PMID- 26363382 TI - Synthetic TRP2 long-peptide and alpha-galactosylceramide formulated into cationic liposomes elicit CD8+ T-cell responses and prevent tumour progression. AB - The lipid antigen alpha-galactosylceramide (alpha-GalCer) is a potent activator of invariant natural killer T-cells (iNKT cells) and can stimulate cytotoxic and anti-tumour immune responses. However optimal responses appear to be induced by alpha-GalCer when cell-based vaccines are delivered intravenously. Here we investigated if co-delivery of protein and peptide antigens along with alpha GalCer in a liposomal formulation could stimulate therapeutic anti-tumour immune responses. Cationic liposomes were inherently immune-stimulatory and induced cytotoxic immune responses when delivered both by intravenous and subcutaneous injection. However, only vaccine delivered intravenously stimulated therapeutic anti-tumour immune responses to a peptide antigen. Surface modification with polyethylene glycol (PEG) did not improve immune responses to either intravenously or subcutaneously delivered vaccines. Immune responses to short and long peptide sequences (CD8 and CD4 epitopes) of the self-antigen tyrosinase related protein 2 (TRP2) as a vaccine antigen, co-delivered with alpha-GalCer in either cationic liposomes or PBS were further examined. Enhanced production of IFN-gamma, increased cytotoxic T-cell responses and tumour survival were observed when a long TRP2-peptide was delivered with alpha-GalCer in cationic liposomes. PMID- 26363381 TI - Protection by novel vaccine candidates, Mycobacterium tuberculosis DeltamosR and DeltaechA7, against challenge with a Mycobacterium tuberculosis Beijing strain. AB - Mycobacterium tuberculosis, the etiological agent of tuberculosis (TB), infects over two billion people, claiming around 1.5 million lives annually. The only vaccine approved for clinical use against this disease is the Bacillus Calmette Guerin (BCG) vaccine. Unfortunately, BCG has limited efficacy against the adult, pulmonary form of tuberculosis. This vaccine was developed from M. bovis with antigen expression and host specificity that differ from M. tuberculosis. To address these problems, we have designed two novel, live attenuated vaccine (LAV) candidates on an M. tuberculosis background: DeltamosR and DeltaechA7. These targeted genes are important to M. tuberculosis pathogenicity during infection. To examine the efficacy of these strains, C57BL/6 mice were vaccinated subcutaneously with either LAV, BCG, or PBS. Both LAV strains persisted up to 16 weeks in the spleens or lungs of vaccinated mice, while eliciting minimal pathology prior to challenge. Following challenge with a selected, high virulence M. tuberculosis Beijing strain, protection was notably greater for both groups of LAV vaccinated animals as compared to BCG at both 30 and 60 days post-challenge. Additionally, vaccination with either DeltamosR or DeltaechA7 elicited an immune response similar to BCG. Although these strains require further development to meet safety standards, this first evidence of protection by these two new, live attenuated vaccine candidates shows promise. PMID- 26363383 TI - Introduction: Management of endometriosis: moving toward a problem-oriented and patient-centered approach. AB - Endometriosis is a protean disease, and its manifestations, associated clinical problems, and possible treatments are numerous. Deep endometriosis that infiltrates multiple pelvic organs should be considered the most severe endometriotic form that poses the most difficult therapeutic uncertainties in both infertility and pelvic pain symptoms limiting quality of life. The available evidence demonstrates that endometriosis is not only a gynecologic disorder but, contrary to previous belief, its impact extends into pregnancy, delivery, and the post-partum period. The old clinical tenet that pregnancy is a cure for endometriosis may be revealed as fallacious. Safe and effective modalities to reduce the risk of the recurrence of symptoms and lesions after conservative surgery for endometriosis are now available. These treatment options should be offered post-operatively to women not immediately seeking conception. Endometriosis is associated with a moderate increase in ovarian cancer risk. However, as there are no definitive demonstrations that endometriosis constitutes per se a pre-neoplastic condition, it seems currently unwise to set-up a screening program to detect undiagnosed endometriosis in asymptomatic women. Endometriosis is not a cancer; therefore a paradigm shift from treatment of lesions to treatment of symptoms is warranted. Management should be shaped on the main clinical problem, taking into consideration a woman's preferences and priorities. Quantitative information should be provided to describe the potential benefits, potential harms, and costs of each treatment alternative. Counseling should be complete and transparent, and the duty of the caring gynecologist is to inform the woman on the pros and cons of each option and support her in the shared decision-making process. The physician should be able to explain in detail all the available treatments, and not only those that the physician prefers or is able to offer. PMID- 26363384 TI - Difference in birth weight of consecutive sibling singletons is not found in oocyte donation when comparing fresh versus frozen embryo replacements. AB - OBJECTIVE: First, to assess if there are any differences in birth weight or gestational length in newborns from egg-donation pregnancies delivering singletons, originating from either fresh or frozen-thawed embryos when they were developed and delivered within the same mothers. Second, to determine if there are any clinical, phenotypic, or laboratory factors influencing this relationship, including the origin of the oocyte (same or different donor), the order of the children (first fresh or first frozen-thawed embryo transfer), the embryo freezing technique (vitrification or slow freezing), the in vitro embryo culture length, and the duration that embryos remained frozen. DESIGN: Retrospective cohorts study. SETTING: University-affiliated infertility centers. PATIENT(S): A total of 360 women undergoing oocyte donation (OD), delivering (>28 weeks) at least two babies, each one from a single pregnancy, originating from at least one fresh and one frozen-thawed embryo transfer, controlling maternal and laboratory characteristics, to test the effect of embryo freezing on children size (n = 731). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Birth weight, gestational age, weight percentile, being large for gestational age (LGA), small for gestational age (SGA), size out of normal range (ONR = LGA + SGA), and macrosomy. RESULT(S): From fresh versus thawed embryos, respectively, mean birth weight of children was 3,183.7 g versus 3,226.4 g, gestational age was 272.1 days versus 268.8 days, and mean weight percentiles were 47.6 versus 50.1. The proportions and corresponding odds ratios (ORs) from fresh versus thawed embryos, respectively, were for LGA 13.6% versus 11.3% (OR 0.81), for SGA 9.4% versus 12.5% (OR 1.37), for ONR 23.1% versus 23.8% (OR 1.04), and for macrosomy 0.3% versus 0.8% (OR 3.1). After adjusting for clinically relevant variables, the ORs were for LGA 0.96, for SGA 1.40, for ONR 1.20, and for macrosomy not computable. None of the stated measures were significantly different. Also, independent analyses run on the origin of the oocytes, cryopreservation technique, cleavage stage of the embryos, and time that embryos remained frozen did not reveal any significant trends. CONCLUSION(S): This study comparing siblings from OD cycles, and eliminating the independent variables that affect early events in pregnancy, revealed no difference in duration of gestation and live birth weights between fetuses obtained after the replacement of fresh or frozen embryos. Moreover, no clinical, phenotypic, or laboratory factors appeared to be relevant, once statistically controlled. PMID- 26363385 TI - Mid-pregnancy, perinatal, and neonatal reproductive endocrinology: a prospective cohort study in twins and singleton control subjects. AB - OBJECTIVE: To answer the questions: Are perinatal reproductive hormone profiles different in case of a twin compared with a singleton pregnancy? Are reproductive endocrine profiles of twin girls influenced by their male co-twin and vice versa? DESIGN: Prospective cohort study from January 2004 to October 2009. SETTING: Not applicable. PATIENT(S): A total of 204 mothers of twins and 248 singleton control subjects, aged >18 years, pregnant with a twin or singleton and no endocrine disease or malignancy. INTERVENTION(S): Blood samples were collected at mid gestation from the mother and at delivery from the mothers and the umbilical cords. Estrogens, androgens, sex hormone-binding globulin, progesterone, and gonadotropins were measured. MAIN OUTCOME MEASURE(S): Hormonal profiles were compared between singletons and twins, different types of twins, and opposite-sex and same-sex twins. RESULT(S): Estrogen and progesterone concentrations were higher in mothers of twins compared with singletons, but twin babies had lower estrogen and progesterone concentrations at birth. Opposite-sex twin girls did not have higher androgens in cord blood compared with same-sex twin girls. Boys of an opposite-sex twin had lower luteinizing hormone concentrations compared with dizygotic twin boys with a brother as a co-twin. CONCLUSION(S): Children from a twin are not overexposed to sex steroids at the time of birth, despite higher concentrations in their mothers, and girls from opposite sex twins do not show androgenic influences from their male co-twin. The female co-twin may influence the hypothalamic-pituitary-testicular axis of her brother via central inhibition. PMID- 26363386 TI - Three-dimensional sperm surface reconstruction: a novel approach to assessing sperm morphology. AB - OBJECTIVE: To create a rapid, inexpensive, efficient, and reproducible real-time three-dimensional (3-D) analysis of viable spermatozoa. Previous studies have demonstrated that abnormal semen profiles are associated with a modest increase in the frequency of sperm chromosomal abnormalities, and that sperm with aberrations in the shape and contours of the head may be carriers of chromatinic defects. Although high-power magnification and enhanced video-generated magnification have been suggested, these techniques are inherently limited by the clarity of the image, the time required for the analysis, and the risk of variable head-positioning during imaging. DESIGN: In vitro experiment. SETTING: University-affiliated infertility research laboratory. PATIENT(S): Anonymous sperm donors. INTERVENTION(S): Individual motile sperm were identified, analyzed at *600 magnification, and a 10-second digital video was obtained. MAIN OUTCOME MEASURE(S): Image-tracking software captured serial photographs of sperm from recorded videos. Images were automatically extracted from each video frame using enhanced correlation coefficient maximization; the general shape of the sperm was extracted via space-carving. The reconstructed image was rotated to permit viewing from any direction, and the final image was rendered through interpolation. RESULT(S): This technique yielded images that enable noninvasive, 3-D, real-time, in vitro assessment of sperm surface morphology. CONCLUSION(S): This proof-of-principle demonstrates that by keeping spermatozoa in a fluid environment, a 3-D sperm-surface reconstruction can be created. This technique can be automated, requires minimal computing power, and utilizes equipment already available in most embryology laboratories. PMID- 26363387 TI - Treatment of pain associated with deep endometriosis: alternatives and evidence. AB - Pain is the most evident clinical manifestation of deep infiltrating endometriosis (DIE). Several hormonal and immunologic mechanisms are markedly altered in DIE compared with superficial peritoneal and ovarian endometriosis, and may explain its most aggressive behavior and the presence of severe pain symptoms. Hormonal therapies, such as combined hormonal contraceptives and progestogens, should be regarded as first-line treatment, as they are efficacious, safe, and well tolerated. Gonadotropin-releasing hormone agonists may be used in patients with symptoms persisting after the administration of first-line therapies. Scanty literature is available for danazol treatment in patients with DIE and, however, it has become less popular due to the high rates of androgenic adverse events (AEs). The partial relief of pain that often is achieved with available therapies and its recurrence after the suspension of the treatment have brought to the development of new therapies (such as aromatase inhibitors, oral GnRH antagonists) that are currently under investigation. Surgical excision of DIE should be considered in patients with pain symptoms persisting after first-line hormonal therapies. The benefits of surgery in terms of pain improvement should be always balanced with the risk of intraoperative complications and for this reason surgical cases should be referred to tertiary centers for the treatment of DIE. A multidisciplinary approach is mandatory in patients with DIE involving the bowel and/or the urinary tract. PMID- 26363388 TI - Access to fertility services by transgender persons: an Ethics Committee opinion. AB - This statement explores the ethical considerations surrounding the provision of fertility services to transgender individuals and concludes that denial of access to fertility services is not justified. PMID- 26363389 TI - Higher pregnancy rates using testicular sperm in men with severe oligospermia. AB - OBJECTIVE: To evaluate assisted reproductive technology (ART) outcomes using testicular sperm in oligospermic men who previously failed to achieve paternity using TUNEL-positive ejaculated sperm. DESIGN: Retrospective cohort. SETTING: Academic medical center. PATIENT(S): Twenty-four oligospermic men who failed one or more ART cycles using ejaculated sperm with TUNEL-positive proportion >7%, and subsequently underwent microsurgical testicular sperm extraction (TESE). INTERVENTION(S): TESE followed by intracytoplasmic sperm injection (ICSI). MAIN OUTCOME MEASURE(S): TUNEL-positive level in ejaculated and testicular sperm; clinical pregnancy. RESULT(S): The mean TUNEL-positive level was 24.5% for ejaculated sperm, and 4.6% for testicular sperm. Clinical pregnancy was achieved in the first ART cycle with testicular sperm in 12 (50%) out of 24 couples. There was no statistically significant difference in maternal and paternal age, maternal gravity and parity, number of previous ART attempts, concentration or motility of retrieved sperm, number of oocytes retrieved, fertilization rate, or number of embryos transferred between couples who did and did not achieve pregnancy. No miscarriages occurred. All 12 pregnancies resulted in the delivery of healthy children. CONCLUSION(S): The percentage of TUNEL-positive cells is lower in testicular sperm for oligospermic men who have abnormal ejaculated sperm DNA fragmentation. The use of testicular sperm for ICSI was associated with a 50% pregnancy and live-birth rate for couples who had previously failed one or more IVF-ICSI cycles with ejaculated sperm. No other clinical predictors of successful pregnancies after the use of surgically retrieved sperm could be identified. In men with elevated TUNEL-positive ejaculated sperm and failed ART, TESE may be considered. PMID- 26363390 TI - Silver nanoparticles coated with natural polysaccharides as models to study AgNP aggregation kinetics using UV-Visible spectrophotometry upon discharge in complex environments. AB - This study provides quantitative information on the aggregation and dissolution behaviour of silver nanoparticles (AgNPs) upon discharge in fresh and sea waters, represented here as NaCl solutions of increasing ionic strength (up to 1M) and natural fjord waters. Natural polysaccharides, sodium alginate (ALG) and gum Arabic (GA), were used as coatings to stabilize the AgNPs and the compounds acted as models to study AgNP aggregation kinetics. The DLVO theory was used to quantitatively describe the interactions between the AgNPs. The stability of AgNPs was established using UV-Visible spectrophotometry, including unique information collected during the first seconds of the aggregaton process. Alginate coating resulted in a moderate stabilization of AgNPs in terms of critical coagulation concentration (~82mM NaCl) and a low dissolution of <10% total Ag in NaCl solutions up to 1M. Gum Arabic coated AgNPs were more strongly stabilized, with ~7-30% size increase up to 77mM NaCl, but only when the silver ion content initially present in solution was low (<10% total Ag). The ALG and GA coated AgNPs showed a strongly enhanced stability in natural fjord waters (ca. 5h required to reduce the area of the surface plasmon resonance band (SPRB) by two fold) compared with NaCl at an equivalent ionic strength (1-2min period for a two fold SPRB reduction). This is ascribed to a stabilizing effect from dissolved organic matter present in natural fjord waters. Interestingly, for AgNP-GA solutions with 40% of total silver present as unreacted silver ions in the NP stock solution, fast aggregation kinetics were observed in NaCl solutions (SPRB area was reduced by ca. 50% within 40-150min), with even more rapid removal in fjord waters, attributed to the high amount of silver-chloride charged species, that interact with the NP coating and/or organic matter and reduce the NPs stabilization. PMID- 26363391 TI - The assessment of water use and reuse through reported data: A US case study. AB - Increasing demands for freshwater make it necessary to find innovative ways to extend the life of our water resources, and to manage them in a sustainable way. Indirect water reuse plays a role in meeting freshwater demands but there is limited documentation of it. There is a need to analyze its current status for water resources planning and conservation, and for understanding how it potentially impacts human health. However, the fact that data are archived in discrete uncoordinated databases by different state and federal entities, limits the capacity to complete holistic analysis of critical resources at large watershed scales. Humans alter the water cycle for food production, manufacturing, energy production, provision of potable water and recreation. Ecosystems services are affected at watershed scales but there are also global scale impacts from greenhouse gas emissions enabled by access to cooling, processing and irrigation water. To better document these issues and to demonstrate the utility of such an analysis, we studied the Wabash River Watershed located in the U.S. Midwest. Data for water extraction, use, discharge, and river flow were collected, curated and reorganized in order to characterize the water use and reuse within the basin. Indirect water reuse was estimated by comparing treated wastewater discharges with stream flows at selected points within the watershed. Results show that during the low flow months of July October, wastewater discharges into the Wabash River basin contributed 82 to 121% of the stream flow, demonstrating that the level of water use and unplanned reuse is significant. These results suggest that intentional water reuse for consumptive purposes such as landscape or agricultural irrigation could have substantial ecological impacts by diminishing stream flow during vulnerable low flow periods. PMID- 26363392 TI - Nitrate bioreduction in redox-variable low permeability sediments. AB - Lowpermeability zone (LPZ) can play an important role as a sink or secondary source in contaminant transport in groundwater system. This study investigated the rate and end product of nitrate bioreduction in LPZ sediments. The sedimentswere fromthe U.S. Department of Energy's Hanford Site,where nitrate is a groundwater contaminant as a by-product of radionuclide waste discharges. The LPZ at the Hanford site consists of two layerswith an oxidized layer on top and reduced layer below. The oxidized layer is directly in contact with the overlying contaminated aquifer, while the reduced layer is in contact with an uncontaminated aquifer below. The experimental results showed that nitrate bioreduction rate and end-product differed significantly in the sediments. The bioreduction rate in the oxidized sediment was significantly faster than that in the reduced one. A significant amount of N2O was accumulated in the reduced sediment; while in the oxidized sediment, N2O was further reduced to N2. RT-PCR analysis revealed that nosZ, the gene that codes for N2O reductase, was below detection limit in the reduced sediment. Batch experiments and kinetic modeling were performed to provide insights into the role of organic carbon bioavailability, biomass growth, and competition between nitrate and its reducing products for electrons fromelectron donors. The results revealed that it is important to consider sediment redox conditions and functional genes in understanding and modeling nitrate bioreduction in subsurface sediments. The results also implied that LPZ sediments can be important sink of nitrate and a potential secondary source of N2O as a nitrate bioreduction product in groundwater. PMID- 26363393 TI - Occurrence of selected antibiotics and antiretroviral drugs in Nairobi River Basin, Kenya. AB - In this paper, we investigated the occurrence of three antibiotics (sulfamethoxazole, trimethoprim and ciprofloxacin) and three antiretroviral (lamivudine, nevirapine and zidovudine) drugs in the Nairobi River Basin, Kenya. The analytical procedure involved extraction using solid phase extraction followed by liquid chromatography-electrospray ionization tandem mass spectrometry (SPE-LC-ESI-MS/MS). In this study, 40 sites were selected for sampling, including 38 sites along the rivers and 2 wastewater treatment effluent sites. All the studied compounds were detected with sulfamethoxazole having the highest detection frequency of 97.5% and ciprofloxacin had the lowest at 60%. The results showed that the concentration of the drugs increased in highly populated regions especially within the informal settlements. The maximum (median) concentrations in the river waters for sulfamethoxazole, trimethoprim, ciprofloxacin, lamivudine, nevirapine and zidovudine in ng/L were 13,800 (1800), 2650 (327), 509 (129), 5430 (1000), 4860 (769), and 7680 (660), respectively. The maximum concentrations in the river waters were generally higher than those of the wastewater treatment plant effluents signifying that the rivers are substantially contaminated by domestic wastewater. The environmental risk was evaluated by calculating the risk quotients (RQs) for algae, daphnia and fish based on the maximum and median concentrations of the analytes in the river basin and was expressed as the ratios of measured environmental concentrations (MEC) to predicted no effect concentrations (PNEC). The RQs ranged from 0 to 507.8 and apart from lamivudine that had a low RQ, all the other analytes had RQ>1 at maximum and median measured concentrations for at least one taxonomic group. The high RQs are indicative of possible adverse ecological effects and calls for corrective and mitigation strategies. PMID- 26363394 TI - Effects of the terbuthylazine metabolite terbuthylazine-desethyl on common carp embryos and larvae. AB - Toxicity of terbuthylazine-desethyl to embryos and larvae of common carp (Cyprinus carpio) was assessed. Based on mortality, the lethal concentration of terbuthylazine-desethyl was estimated to be 31days LC50=441.6MUg/L. Carp exposed to terbuthylazine-desethyl at 1800MUg/L exhibited lower weight and length at 7days of exposure compared to the control group. By day 20, carp exposed to 900MUg/L terbuthylazine-desethyl showed lower weight and length compared to control group. Terbuthylazine-desethyl in concentrations (180, 900, and 1800MUg/L) caused delay in ontogenetic development. Total superoxide dismutase activity was significantly lower in all exposed groups. Exposure to 180 and 900MUg/L terbuthylazine-desethyl was associated with alteration of the caudal kidney tubular system including peritubular dilatation detachment of epithelial cells from the basal lamina, and focal autolytic disintegration of the tubular epithelia. Chronic terbuthylazine-desethyl exposure affected survival, growth, ontogenetic development, and the antioxidant system and caused pathological changes to the caudal kidney. PMID- 26363395 TI - Upscaling NZ-DNDC using a regression based meta-model to estimate direct N2O emissions from New Zealand grazed pastures. AB - The availability of detailed input data frequently limits the application of process-based models at large scale. In this study, we produced simplified meta models of the simulated nitrous oxide (N2O) emission factors (EF) using NZ-DNDC. Monte Carlo simulations were performed and the results investigated using multiple regression analysis to produce simplified meta-models of EF. These meta models were then used to estimate direct N2O emissions from grazed pastures in New Zealand. New Zealand EF maps were generated using the meta-models with data from national scale soil maps. Direct emissions of N2O from grazed pasture were calculated by multiplying the EF map with a nitrogen (N) input map. Three meta models were considered. Model 1 included only the soil organic carbon in the top 30cm (SOC30), Model 2 also included a clay content factor, and Model 3 added the interaction between SOC30 and clay. The median annual national direct N2O emissions from grazed pastures estimated using each model (assuming model errors were purely random) were: 9.6GgN (Model 1), 13.6GgN (Model 2), and 11.9GgN (Model 3). These values corresponded to an average EF of 0.53%, 0.75% and 0.63% respectively, while the corresponding average EF using New Zealand national inventory values was 0.67%. If the model error can be assumed to be independent for each pixel then the 95% confidence interval for the N2O emissions was of the order of +/-0.4-0.7%, which is much lower than existing methods. However, spatial correlations in the model errors could invalidate this assumption. Under the extreme assumption that the model error for each pixel was identical the 95% confidence interval was approximately +/-100-200%. Therefore further work is needed to assess the degree of spatial correlation in the model errors. PMID- 26363396 TI - Evaluation of the ornithogenic influence on the trophic state of East Mediterranean wetland ecosystem using trend analysis. AB - The Great Rift Valley portion of the East African-Eurasian Migratory Flyway is extremely important globally because of the numbers (>500 million) and diversity of seasonal traveling birds. The construction of the Agmon wetland (1.1km(2)) in the Hula Valley, Israel in 1994 and a change in crop type and rotation has attracted increasing number of Eurasian cranes (Grus grus) to winter in the wetland (>40,000 in 2014). The birds are fed in an area of 100ha and roost during the night in the wetland for protection from predators. Feeding practices have yielded an eco-tourism bonanza with over 400,000 visitors annually. However, this practice may have negative impacts on the trophic state of the wetland. We performed trend analyses using monthly means of selected constituents collected from mid-1994 to 2014. The temporal distribution of TN and TP concentrations in the inlets did not change with time. The concentrations of TN and TP in the outlet increased significantly during the earlier monitoring period. Kendall Theil regression showed that TP concentrations in the outlet increased significantly from a monthly mean of 180MUgL(-1) in 2010 to a monthly mean of 260MUgL(-1) in 2014. Similarly, the results of chlorophyll a concentrations in the outlet showed a sharp upturn in the latter part of the series from a mean of 66mgL(-1) in 2010 to a mean of 122mgL(-1) in 2014. The concurrent increase of TP and chlorophyll a, the two most important parameters affecting a waterbody trophic index coincided with the observed increase in the number of roosting cranes in the wetland. Hence, we assume that the continued increases in TP concentrations could transform the wetland from a mild eutrophic to a permanent hypereutrophic state. Reducing the number of roosting cranes may prevent this from happening. PMID- 26363397 TI - Nitrate pollution of groundwater; all right..., but nothing else? AB - Contamination from agricultural sources and, in particular, nitrate pollution, is one of the main concerns in groundwater management. However, this type of pollution entails the entrance of other substances into the aquifer, as well as it may promote other processes. In this study, we deal with hydrochemical and isotopic analysis of groundwater samples from four distinct zones in Catalonia (NE Spain), which include 5 different aquifer types, to investigate the influence of fertilization on the overall hydrochemical composition of groundwater. Results indicate that intense fertilizer application, causing high nitrate pollution in aquifers, also homogenize the contents of the major dissolved ions (i.e.; Cl(-), SO4(2-), Ca(2+), Na(+), K(+), and Mg(2+)). Thus, when groundwater in igneous and sedimentary aquifers is compared, significant differences are observed under natural conditions for Cl(-), Na(+) and Ca(2+) (with p-values ranging from <0.001 to 0.038), and when high nitrate concentrations occur, these differences are reduced (most p-values ranged between 0.054 and 0.978). Moreover, positive linear relationships between nitrate and some ions are found indicating the magnitude of the fertilization impact on groundwater hydrochemistry (with R(2) values of 0.490, 0.609 and 0.470, for SO4(2-), Ca(2+) and Cl(-), respectively). Nevertheless, the increasing concentration of specific ions is not only attributed to agricultural pollution, but to their enhancing effect upon the biogeochemical processes that control water-rock interactions. Such results raise awareness that these processes should be evaluated in advance in order to assess an adequate groundwater resources management. PMID- 26363398 TI - Transfer of elements relevant to nuclear fuel cycle from soil to boreal plants and animals in experimental meso- and microcosms. AB - Uranium (U), cobalt (Co), molybdenum (Mo), nickel (Ni), lead (Pb), thorium (Th) and zinc (Zn) occur naturally in soil but their radioactive isotopes can also be released into the environment during the nuclear fuel cycle. The transfer of these elements was studied in three different trophic levels in experimental mesocosms containing downy birch (Betula pubescens), narrow buckler fern (Dryopteris carthusiana) and Scandinavian small-reed (Calamagrostis purpurea ssp. Phragmitoides) as producers, snails (Arianta arbostorum) as herbivores, and earthworms (Lumbricus terrestris) as decomposers. To determine more precisely whether the element uptake of snails is mainly via their food (birch leaves) or both via soil and food, a separate microcosm experiment was also performed. The element uptake of snails did not generally depend on the presence of soil, indicating that the main uptake route was food, except for U, where soil contact was important for uptake when soil U concentration was high. Transfer of elements from soil to plants was not linear, i.e. it was not correctly described by constant concentration ratios (CR) commonly applied in radioecological modeling. Similar nonlinear transfer was found for the invertebrate animals included in this study: elements other than U were taken up more efficiently when element concentration in soil or food was low. PMID- 26363399 TI - Spatial distribution, temporal variation and risks of parabens and their chlorinated derivatives in urban surface water in Beijing, China. AB - The occurrence and distribution of 13 target compounds, including eight parabens, four chlorinated parabens and p-hydroxybenzoic acid (PHBA), were detected in surface water samples at 35 sampling sites in the Beijing River system, China. The surface water samples were collected from the main rivers and lakes in the urban area monthly from July 2013 to June 2014 (except the frozen period). Laboratory analyses revealed that parabens were ubiquitous in the surface water of Beijing. PHBA was the predominant compound in the surface water samples, with the average concentration of 239ngL(-1), followed by the total amount of chlorinated parabens (average 50.1ng/L) and parabens (average 44.3ng/L). It is noteworthy that octylparaben with longer chain was firstly detected in the surface water. Significant difference was observed for paraben concentrations from different sampling sites, and the highest level of parabens was found in the Xiaotaihou River, which was mainly due to the untreated sewage discharge. Seasonal variation of target compounds in the urban surface water was also studied, and parabens exhibited a different temporal variation from chlorinated derivatives. A combination of factors including high residual chlorine level and water temperature as well as intense ultraviolet radiation might enhance the persistence of chlorinated parabens in chlorinated water during the wet season. Risk assessment showed that parabens and their chlorinated derivatives are not likely to produce biological effects on aquatic ecosystems at current levels in the surface water of Beijing. PMID- 26363400 TI - Association between indoor air pollutant exposure and blood pressure and heart rate in subjects according to body mass index. AB - This study investigates the effects of high body mass index (BMI) of subjects on individual who exhibited high cardiovascular disease indexes with blood pressure (BP) and heart rate (HR) when exposed to high levels of indoor air pollutants. We collected 115 office workers, and measured their systolic blood pressure (SBP), diastolic blood pressure (DBP) and HR at the end of the workday. The subjects were divided into three groups according to BMI: 18-24 (normal weight), 24-27 (overweight) and >27 (obese). This study also measured the levels of carbon dioxide (CO2), total volatile organic compounds (TVOC), particulate matter with an aerodynamic diameter less than 2.5MUm (PM2.5), as well as the bacteria and fungi in the subjects' work-places. The pollutant effects were divided by median. Two-way analysis of variance (ANOVA) was used to analyze the health effects of indoor air pollution exposure according to BMI. Our study showed that higher levels of SBP, DBP and HR occurred in subjects who were overweight or obese as compared to those with normal weight. Moreover, there was higher level of SBP in subjects who were overweight or obese when they were exposed to higher levels of TVOC and fungi (p<0.05). We also found higher value for DBP and HR with increasing BMI to be associated with exposure to higher TVOC levels. This study suggests that individuals with higher BMI have higher cardiovascular disease risk when they are exposed to poor indoor air quality (IAQ), and specifically in terms of TVOC. PMID- 26363401 TI - Temporal trends for inflow of perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA) to Tokyo Bay, Japan, estimated by a receptor-oriented approach. AB - We estimated inflow rates of perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA) to Tokyo Bay, Japan, between February 2004 and February 2011 by a receptor-oriented approach based on quarterly samplings of the bay water. Temporal trends in these inflow rates are an important basis for evaluating changes in PFOS and PFOA emissions in the Tokyo Bay catchment basin. A mixing model estimated the average concentrations of these compounds in the freshwater inflow to the bay, which were then multiplied by estimated freshwater inflow rates to obtain the inflow rates of these compounds. The receptor-oriented approach enabled us to comprehensively cover inflow to the bay, including inflow via direct discharge to the bay. On a logarithmic basis, the rate of inflow for PFOS decreased gradually, particularly after 2006, whereas that for PFOA exhibited a marked stepwise decrease from 2006 to 2007. The rate of inflow for PFOS decreased from 730kg/y during 2004-2006 to 160kg/y in 2010, whereas that for PFOA decreased from 2000kg/y during 2004-2006 to 290kg/y in 2010. These reductions probably reflected reductions in the use and emission of these compounds and their precursors in the Tokyo Bay catchment basin. Our estimated per-person inflow rates (i.e., inflow rates divided by the estimated population in the basin) for PFOS were generally comparable to previously reported per person waterborne emission rates in Japan and other countries, whereas those for PFOA were generally higher than previously reported per-person waterborne emission rates. A comparison with previous estimates of household emission rates of these compounds suggested that our inflow estimates included a considerable contribution from point industrial sources. PMID- 26363402 TI - Pharmaceutical concentrations in screened municipal wastewaters in Victoria, British Columbia: A comparison with prescription rates and predicted concentrations. AB - Pharmaceuticals and personal care products (PPCPs) are emerging chemicals of concern detected in surface waters globally. Recent reviews advocate that PPCP occurrence, fate, and exposure need to be better predicted and characterized. The use of pharmaceutical prescription rates to estimate PPCP concentrations in the environment has been suggested. Concentrations of 7 pharmaceuticals (acetylsalicylic acid, diclofenac, fenoprofen, gemfibrozil, ibuprofen, ketoprofen, and naproxen) were measured in municipal wastewater using gas chromatography/ion trap-tandem mass spectroscopy (GC/IT-MS/MS). Subregional pharmaceutical prescription data were investigated to determine whether they could predict measured effluent concentrations (MECs) in wastewaters. Predicted effluent concentrations (PECs) for 5 of the 7 pharmaceuticals were within 2-fold agreement of the MECs when the fraction of parent pharmaceutical excreted was not considered. When the fraction of parent pharmaceutical excreted was considered, the respective PECs decreased, and most were within an order of magnitude of the MECs. Regression relationships of monthly PECs versus MECs were statistically significant (p < 0.05) but weak (R(2) = 0.18-0.56) for all pharmaceuticals except ketoprofen. This suggests high variability in the data and may be the result of factors influencing MECs such as the analytical methods used, wastewater sampling frequency, and methodology. The PECs were based solely on prescription rates and did not account for inputs of pharmaceuticals that had a significant over-the counter component or were from other sources (e.g., hospitals). PMID- 26363403 TI - Education in infection control: A need for European certification. AB - Healthcare-associated infections are common adverse events in acute-care medicine, causing significant morbidity and mortality. There has been a significant increase in the commitment to infection prevention and control (IPC) among European countries in recent years. However, there is still heterogeneity in training opportunities and IPC qualifications. The European Union promotes the harmonization of IPC strategies among member states. The European Centre for Disease Prevention and Control (ECDC)-commissioned Training in Infection Control in Europe project sets the stage for harmonization of IPC activities in Europe by issuing a list of core competencies for IPC professionals. European certification of IPC training and professionals would be the next logical step, which must be achieved by close collaboration between different stakeholders in Europe such as the ECDC, the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), the European Union of Medical Specialities, and the national IPC societies. Therefore, the ESCMID has launched the new European Committee on Infection Control to take the lead in the implementation of a European (board) certificate for IPC professionals. PMID- 26363405 TI - Diagnosis of Aerococcus urinae infections: Importance of matrix-assisted laser desorption ionization time-of-flight mass spectrometry and broad-range 16S rDNA PCR. PMID- 26363404 TI - Strain features and distributions in pneumococci from children with invasive disease before and after 13-valent conjugate vaccine implementation in the USA. AB - The effect of second-generation pneumococcal conjugate vaccines on invasive pneumococcal disease (IPD) strain distributions have not yet been well described. We analysed IPD isolates recovered from children aged <5 years through Active Bacterial Core surveillance before (2008-2009; n = 828) and after (2011-2013; n = 600) 13-valent pneumococcal conjugate vaccine (PCV13) implementation. We employed conventional testing, PCR/electrospray ionization mass spectrometry and whole genome sequence (WGS) analysis to identify serotypes, resistance features, genotypes, and pilus types. PCV13, licensed in February 2010, effectively targeted all major 19A and 7F genotypes, and decreased antimicrobial resistance, primarily owing to removal of the 19A/ST320 complex. The strain complex contributing most to the remaining beta-lactam resistance during 2011-2013 was 35B/ST558. Significant emergence of non-vaccine clonal complexes was not evident. Because of the removal of vaccine serotype strains, positivity for one or both pilus types (PI-1 and PI-2) decreased in the post-PCV13 years 2011-2013 relative to 2008-2009 (decreases of 32-55% for PI-1, and >95% for PI-2 and combined PI-1 + PI-2). beta-Lactam susceptibility phenotypes correlated consistently with transpeptidase region sequence combinations of the three major penicillin-binding proteins (PBPs) determined through WGS analysis. Other major resistance features were predictable by DNA signatures from WGS analysis. Multilocus sequence data combined with PBP combinations identified progeny, serotype donors and recipient strains in serotype switch events. PCV13 decreased the frequency of all PCV13 serotype clones and concurrently decreased the frequency of strain subsets with resistance and/or adherence features conducive to successful carriage. Our results serve as a reference describing key features of current paediatric IPD strains in the USA after PCV13 implementation. PMID- 26363406 TI - Minimum requirements in infection control. AB - Infection control (IC) activities are facing new challenges, but the resources dedicated to IC are too frequently insufficient. Heterogeneity of resources among centres and countries is huge, a fact that at least partly explains the differences in the results obtained. In this article, we review and discuss the available recommendations for minimum requirements in IC related to organizational aspects, IC staffing and the training of these staff, ward staffing, structural issues, and microbiological support. A professional-based consensus on the minimum requirements for IC in European centres based on present challenges and societal demands is needed. PMID- 26363407 TI - MW polyomavirus and STL polyomavirus present in tonsillar tissues from children with chronic tonsillar disease. AB - We aimed to explore the frequency of all 13 human polyomaviruses (HPyVs), especially MW polyomavirus (MWPyV) and STL polyomavirus (STLPyV), in tonsillar tissues from Chinese children with chronic tonsillar disease. We examined 99 swabs from mucosal surfaces of palatine tonsils, in which six HPyVs were detected. MWPyV and STLPyV were each detected in two samples. This provides new evidence for the hypothesis that the lymphoid system may play a role in HPyV infection and persistence. We need to define their role in tonsillar disease in the future. PMID- 26363408 TI - Transcriptome analysis of the pearl oyster (Pinctada fucata) hemocytes in response to Vibrio alginolyticus infection. AB - The pearl oyster Pinctada fucata is cultured widely for production of marine pearls in China, while mass mortalities, likely related to pathogenic infections, have occurred frequently in juvenile, mother and operated oysters. To address this issue, understanding host defense mechanisms of P. fucata against pathogenic challenge is extremely important. In the present study, a comparative analysis of hemocyte transcriptomes of P. fucata before and after Vibrio alginolyticus infection was conducted using the Illumina/Hiseq-2000 RNA-Seq technology. A total of 56,345,139 clean reads were generated and then assembled into 74,007 unigenes with an average length of 680 bp and an N50 of 1197 bp. Unigenes were annotated by comparing against non-redundant protein sequence (nr), non-redundant nucleotide (nt), Swiss-Prot, Pfam, Gene Ontology database (GO), Clusters of Orthologous Groups (COG) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, and 29,615 unigenes (40.01%) were annotated in at least one database. There were 636 genes (518 up-regulated and 118 down-regulated) that were significantly differentially expressed after bacterial challenge, and among which 369 were associated with 122 pathways, including classical immune-related pathways, such as 'MAPK signaling pathway', 'Chemokine signaling pathway', 'Apoptosis' and 'Wnt signaling pathway'. These findings provide information on the pearl oyster innate immunity and may contribute to developing strategies for management of diseases and long-term sustainability of P. fucata culture. PMID- 26363409 TI - Ex vivo lymphocyte phenotyping during Plasmodium falciparum sporozoite immunization in humans. AB - Immunization of malaria-naive volunteers under chemoprophylaxis with Plasmodium falciparum sporozoites (CPS) efficiently and reproducibly induces sterile protection and thus constitutes an excellent model to study protective immune responses against malaria. Here, we performed the first longitudinal assessment of lymphocyte activation and differentiation kinetics during sporozoite immunization in 15 volunteers by ex vivo lymphocyte flow cytometry analysis. Both CD4 and CD8 T cells as well as gammadeltaT cells, NK cells and CD3+ CD56+ cells showed increased activation and proliferation following immunization. Transient induction of the transcription factor T-bet and the cytotoxic molecule granzyme B indicated a role of Th1 responses and cytotoxic T cells in CPS-induced immunity. The absolute number of gammadeltaT cells as well as the proportion of granzyme B containing gammadeltaT cells showed a significant and sustained increase. Regulatory T-cell (Treg) proliferation was significantly higher after the second immunization in subjects subsequently not protected against challenge infection. These findings indicate an important role for gammadeltaT cells, Th1 and cytotoxic responses in whole sporozoite immunization with a possibly suppressive role of Tregs. PMID- 26363410 TI - Gestational Age and Autism Spectrum Disorder: Trends in Risk Over Time. AB - Autism Spectrum Disorder (ASD) is a serious neurodevelopmental disorder. Several previous studies have identified preterm birth as a risk factor for ASD but none has studied whether the association between gestational age and ASD has changed over time. This is a Danish population-based follow-up study including live-born singletons born in Denmark between 1980 and 2009, identified in the Danish Medical Birth Registry, a study population of 1,775,397 children. We used a Cox regression model combined with spline to study the risk for ASD by gestational age across three decades of birth cohorts. We included 19,020 children diagnosed with ASD. Across all birth year cohorts, we found that the risk of being diagnosed with ASD increased with lower gestational age (P-value: <0.01). Across all gestational weeks, we found a statistically significant higher risk estimates in birth cohort 1980 to 1989, compared to birth cohorts 1990 to 1999 and 2000 to 2009, respectively. No statistically significant difference in risk estimates was observed between birth cohort 1990 to 1999 and 2000 to 2009. The observed time trend in risk of ASD after preterm birth may reflect: (1) a change in the risk profile of persons with ASD due to the broadening of ASD diagnostic criteria over time; or (2) improved neonatal care for low GA infants, which has reduced risk of adverse outcomes like ASD in preterm children. PMID- 26363411 TI - The population genomics of rapid adaptation: disentangling signatures of selection and demography in white sands lizards. AB - Understanding the process of adaptation during rapid environmental change remains one of the central focal points of evolutionary biology. The recently formed White Sands system of southern New Mexico offers an outstanding example of rapid adaptation, with a variety of species having rapidly evolved blanched forms on the dunes that contrast with their close relatives in the surrounding dark soil habitat. In this study, we focus on two of the White Sands lizard species, Sceloporus cowlesi and Aspidoscelis inornata, for which previous research has linked mutations in the melanocortin-1 receptor gene (Mc1r) to blanched coloration. We sampled populations both on and off the dunes and used a custom sequence capture assay based on probed fosmid libraries to obtain >50 kb of sequence around Mc1r and hundreds of other random genomic locations. We then used model-based statistical inference methods to describe the demographic and adaptive history characterizing the colonization of White Sands. We identified a number of similarities between the two focal species, including strong evidence of selection in the blanched populations in the Mc1r region. We also found important differences between the species, suggesting different colonization times, different genetic architecture underlying the blanched phenotype and different ages of the beneficial alleles. Finally, the beneficial allele is dominant in S. cowlesi and recessive in A. inornata, allowing for a rare empirical test of theoretically expected patterns of selective sweeps under these differing models. PMID- 26363412 TI - An Open Conversation on Using Eye-Gaze Methods in Studies of Neurodevelopmental Disorders. AB - PURPOSE: Eye-gaze methods have the potential to advance the study of neurodevelopmental disorders. Despite their increasing use, challenges arise in using these methods with individuals with neurodevelopmental disorders and in reporting sufficient methodological detail such that the resulting research is replicable and interpretable. METHOD: This tutorial presents key considerations involved in designing and conducting eye-gaze studies for individuals with neurodevelopmental disorders and proposes conventions for reporting the results of such studies. RESULTS: Methodological decisions (e.g., whether to use automated eye tracking or manual coding, implementing strategies to scaffold children's performance, defining valid trials) have cascading effects on the conclusions drawn from eye-gaze data. Research reports that include specific information about procedures, missing data, and selection of participants will facilitate interpretation and replication. CONCLUSIONS: Eye-gaze methods provide exciting opportunities for studying neurodevelopmental disorders. Open discussion of the issues presented in this tutorial will improve the pace of productivity and the impact of advances in research on neurodevelopmental disorders. PMID- 26363413 TI - Prophylactic levofloxacin in pediatric neutropenic patients during autologous hematopoietic stem cell transplantation. AB - BACKGROUND: Using fluoroquinolone prophylaxis in pediatric neutropenic patients is a controversial issue due to the concern about emergence of resistant strains in addition to the lack of pediatric studies. This study was performed to assess the effectiveness of levofloxacin prophylaxis in pediatric patients during autologous stem cell transplantation. METHODS: This was an observational study of pediatric patients who underwent autologous stem cell transplantation, comparing patients who received levofloxacin prophylaxis to historical controls. RESULTS: A total of 96 patients were included (46 patients in the control group and 50 patients received levofloxacin). The median duration till onset of first fever was 11 d in the control group as compared to 15 d in patients who received levofloxacin (p <= 0.001). The incidence of infectious complications was higher in patients without levofloxacin (4/46) than those with levofloxacin (1/50). The median duration of empirical antibiotic use was 10 d in the levofloxacin group compared with 14 d in the control group (p < 0.001). CONCLUSION: Levofloxacin prophylaxis delayed first spike of fever, decreased the incidence of septic complications, and shortened the duration of empiric antibiotic use, but its impact on emergence of resistant organisms should be closely monitored. PMID- 26363414 TI - Comment on "Are repeated assisted reproductive technology treatments and an unsuccessful outcome risk factors for unipolar depression in infertile women?". PMID- 26363415 TI - Measuring the visual salience of alignments by their non-accidentalness. AB - Quantitative approaches are part of the understanding of contour integration and the Gestalt law of good continuation. The present study introduces a new quantitative approach based on the a contrario theory, which formalizes the non accidentalness principle for good continuation. This model yields an ideal observer algorithm, able to detect non-accidental alignments in Gabor patterns. More precisely, this parameterless algorithm associates with each candidate percept a measure, the Number of False Alarms (NFA), quantifying its degree of masking. To evaluate the approach, we compared this ideal observer with the human attentive performance on three experiments of straight contours detection in arrays of Gabor patches. The experiments showed a strong correlation between the detectability of the target stimuli and their degree of non-accidentalness, as measured by our model. What is more, the algorithm's detection curves were very similar to the ones of human subjects. This fact seems to validate our proposed measurement method as a convenient way to predict the visibility of alignments. This framework could be generalized to other Gestalts. PMID- 26363416 TI - Depletion of the AMPAR reserve pool impairs synaptic plasticity in a model of hepatic encephalopathy. AB - Hepatic encephalopathy (HE) is the most common neuropsychiatric complication of acute or chronic liver failure. Clinical symptoms include cognitive and intellectual dysfunction as well as impaired motor activity and coordination. There is general consensus that increased levels of ammonia play a central role in the pathogenesis of HE. However, it is still elusive how cognitive performance including the ability to learn and memorize information is affected by ammonia at molecular levels. In the present study, we have employed a neuroglial co-culture model, which preserves neuroglial interplay but allows for cell-type specific molecular and functional analyses, to investigate glutamatergic neurotransmission under conditions of high ammonia. Chronic exposure to ammonia significantly reduced neuronal mRNA and protein expression of AMPA-subtype glutamate receptors (AMPARs), which mediate most fast excitatory neurotransmission in the brain. Surprisingly, neurons were able to fully maintain basal glutamatergic neurotransmission as recorded by AMPAR-mediated miniature excitatory postsynaptic currents (mEPSCs) even when >50% of total AMPARs were lost. However, long lasting, activity-dependent changes in the efficacy of synaptic communication, which model the capability of the brain to learn and store information, were severely constrained. Whereas synaptic efficacy could still be depressed, an increase in synaptic strength was abolished. We conclude that neurons retain basal glutamatergic transmission at the expense of the extrasynaptic population of AMPARs, which is revealed when the extrasynaptic reserve pool is recruited in vain for synaptic potentiation. Our findings thus offer a molecular model, which might not only explain impaired synaptic plasticity in HE but also in other neurological diseases accompanied by a decrease in extrasynaptic AMPAR expression. PMID- 26363417 TI - Investigating acute satiation and meal termination effects of a commercial lipid emulsion: A breakfast meal study. AB - BACKGROUND: Early clinical studies showed the commercial lipid emulsion FabulessTM to decrease energy intake (EI) and prevent weight regain, but later studies have failed to confirm this finding. Where appetite suppression has been observed it is commonly attributed to the ileal brake, where emulsified fats pass undigested to the distal small intestine and promote later satiety, but satiety profiles suggest possible transient effects within 15 min. The aim of this study was to determine whether this emulsion promotes short-term satiation and meal termination. METHODS: In a randomised cross-over intervention 18 lean men were given 4 lipid preloads immediately prior to a breakfast meal, during which ad libitum food consumption, time to meal termination and VAS-rated appetite scores were measured. Preloads were given as lipid emulsion and lipid control, both alone as a 'shot' and combined with a dairy yoghurt: (i) lipid emulsion alone (LE, FabulessTM 4.2g lipid, 0.2MJ), (ii) lipid control alone (LC, 4.2g lipid, 0.2 MJ), (iii) LE+yoghurt (1.2 MJ), (iv) LC+yoghurt (1.2MJ). RESULTS: Whilst both yoghurt preloads suppressed EI at breakfast relative to the 'shots', as expected, neither lipid emulsion suppressed EI or triggered more rapid meal termination when compared to energy matched lipid controls (P>0.05). There was also no difference in VAS-assessed appetite scores between emulsion and control, for either preload. CONCLUSIONS: When consumed with a meal there was no evidence in lean men that this commercial lipid emulsion promotes satiation or suppresses short-term food intake. PMID- 26363418 TI - Association of 5-HTTLPR polymorphism with smoking behaviors: A meta-analysis. AB - Published articles reported controversial results about the association of 5 HTTLPR polymorphism with the risk of smoking behaviors. A meta-analysis was performed to assess the association between 5-HTTLPR polymorphism and smoking behaviors. A comprehensive search was conducted to identify studies (from January, 1990 to December, 2014) of the aforementioned association. The Q test and the I(2) statistic were used to examine between-study heterogeneity. Fixed or random effect model was selected based on heterogeneity test among studies. Meta regression was used to explore the potential sources of between-study heterogeneity. Publication bias was estimated using funnel plots and Harbord test. Twenty-one published articles were included. Overall, we didn't find any significant association of 5-HTTLPR polymorphism with smoking initiation and smoking cessation in any of allele, dominant and recessive models. In the subgroup analysis stratified by ethnicity (Caucasian and Asian) or by whether smokers accepted the treatment for smoking cessation or not (Yes/No), there were still no significant associations detected in all genetic models. In conclusion, this meta-analysis suggested that there might be no association of 5-HTTLPR polymorphism with the risk of smoking behaviors. Further studies are needed to confirm these conclusions. PMID- 26363419 TI - Pleasure as an ally of healthy eating? Contrasting visceral and Epicurean eating pleasure and their association with portion size preferences and wellbeing. AB - Research on overeating and self-regulation has associated eating pleasure with short-term visceral impulses triggered by hunger, external cues, or internal emotional urges. Drawing on research on the social and cultural dimensions of eating, we contrast this approach with what we call "Epicurean" eating pleasure, which is the enduring pleasure derived from the aesthetic appreciation of the sensory and symbolic value of the food. To contrast both approaches, we develop and test a scale measuring Epicurean eating pleasure tendencies and show that they are distinct from the tendency to experience visceral pleasure (measured using the external eating and emotional eating scales). We find that Epicurean eating pleasure is more prevalent among women than men but is independent of age, income and education. Unlike visceral eating pleasure tendencies, Epicurean eating tendencies are associated with a preference for smaller food portions and higher wellbeing, and not associated with higher BMI. Overall, we argue that the moralizing approach equating the pleasure of eating with 'low-level' visceral urges should give way to a more holistic approach which recognizes the positive role of Epicurean eating pleasure in healthy eating and wellbeing. PMID- 26363420 TI - Eating in response to exercise cues: Role of self-control fatigue, exercise habits, and eating restraint. AB - Identifying moderators of compensatory eating is important for understanding the failure of many people to lose weight in response to increased exercise levels. A previous study demonstrated that individuals shown action words (e.g., "active" or "go") were primed by these words to increase energy intake. Further studies have demonstrated that individual differences (e.g. differences in body mass) affect susceptibility to relevant priming cues. Based on these findings, this study examined individual differences, including exercise habits, tendencies toward compensatory eating, dietary restraint, and body mass that may serve as moderators of compensatory eating in the context of conceptual priming. A 2 * 2 design was utilized to analyze the effects of both priming and a self-control task on energy intake. Participants were presented with several snack foods under the guise of a taste test, with energy intake (kcal) during this taste test as the primary outcome variable. Results of this study indicate that, among those with higher baseline levels of exercise, lower energy intake was found for those exposed to exercise cues relative to those who did not receive these cues. In addition, the influence of the self-control fatigue condition was dependent on body mass index. PMID- 26363421 TI - Cultural specificity in food choice - The case of ethnography in Japan. AB - Previous studies examining food choice from a cross-cultural perspective were based primarily on quantitative research using the Food Choice Questionnaire (FCQ). This study suggests ethnography as a complementary research method in cross-cultural food choice studies. While use of the FCQ resulted in findings of cultural differences in food choice processes, within a preliminary motive list, ethnography allows the exploration of new, possibly culture-specific motives for food choice. Moreover, ethnography allows a deeper understanding of the cultural background of food choice processes in a studied culture. Using Japan as a case study, this research demonstrates the use of ethnography to argue that variety is a primary motive for food choice in contemporary Japanese culture. Variety is hence regarded here as a part of a larger food culture attribute, an "adventurous palate," which can also provide a background for previous FCQ findings (Prescott, Young, O'neill, Yau, & Stevens, 2002). PMID- 26363422 TI - The placemat protocol: Measuring preschoolers' healthy-meal schemas with pretend meals. AB - Nutrition instruction can lead to more healthful food choices among children, but little is known about preschoolers' healthy-meal schemas because there are few developmentally appropriate measures. This study validated the Placemat Protocol, a novel measure of preschooler healthy-meal schemas using realistic food models to assemble pretend meals. Preschoolers (N = 247, mean age 4 years 8 months) created 2 meals (preferred and healthy), completed measures of verbal nutrition knowledge and vocabulary, and were weighed and measured for BMI. Parents reported healthy eating guidance, child dietary intake, and family demographics. Children used an average of 5.1 energy-dense (ED) and 3.4 nutrient-dense (ND) foods for their preferred meal, but reversed the ratio to 3.1 ED and 5.1 ND foods for their healthy meal. Healthy meals contained fewer estimated kcal, less fat, less sugar, and more fiber than preferred meals. Meal differences held for younger children, children with lower verbal nutrition knowledge and vocabulary, and child subgroups at higher risk for obesity. Placemat Protocol data correlated with parent healthy eating guidance and child obesogenic dietary intake as expected. The Placemat Protocol shows promise for assessing developing healthy-meal schemas before children can fully articulate their knowledge on verbal measures. PMID- 26363423 TI - Using the animal to the last bit: Consumer preferences for different beef cuts. AB - Meat is expensive to produce, making it is essential to understand the importance consumers pay to different meat cuts. Previous research on consumers' meat choices has mainly focused on meat species, while consumer preferences for meat cuts has so far only received limited interest. The aim of this study is to shed some light into this relatively unexplored area by answering four research questions. First, this study intends to show the relative importance meat cuts play in relation to other extrinsic product attributes. Secondly, this paper looks into differences in choice criteria between regular and special occasions. Third, consumer segments that differ in their preferences and beef purchase are identified, and, finally, the meat purchase portfolios of these segments are revealed. A stated preference methodology of a discrete choice experiment with cut-specific prices covering several meat cuts simultaneously is proposed to answer the research questions. The sample consists of 1500 respondents representative of the Italian population in terms of age, gender and geographic location The results shows that meat cut is the most important factor when choosing bovine meat followed by quality certification (origin), production technique, the type of breed and price. In terms of consumption occasions, we observe significantly lower price sensitivity for marbled steaks and cutlets for special occasions compared to normal occasions. Segmentation analysis shows that while the choices of two segments (comprising about 40% of the sample) are mostly driven by extrinsic product attributes, the remaining segments are mostly driven by meat cuts. These varying preferences are also reflected in the purchase portfolios of the different segments, while less variability is detected from a socio-demographic perspective. PMID- 26363424 TI - Gait analysis in a mouse model resembling Leigh disease. AB - Leigh disease (LD) is one of the clinical phenotypes of mitochondrial OXPHOS disorders and also known as sub-acute necrotizing encephalomyelopathy. The disease has an incidence of 1 in 77,000 live births. Symptoms typically begin early in life and prognosis for LD patients is poor. Currently, no clinically effective treatments are available. Suitable animal and cellular models are necessary for the understanding of the neuropathology and the development of successful new therapeutic strategies. In this study we used the Ndufs4 knockout (Ndufs4(-/-)) mouse, a model of mitochondrial complex I deficiency. Ndusf4(-/-) mice exhibit progressive neurodegeneration, which closely resemble the human LD phenotype. When dissecting behavioral abnormalities in animal models it is of great importance to apply translational tools that are clinically relevant. To distinguish gait abnormalities in patients, simple walking tests can be assessed, but in animals this is not easy. This study is the first to demonstrate automated CatWalk gait analysis in the Ndufs4(-/-) mouse model. Marked differences were noted between Ndufs4(-/-) and control mice in dynamic, static, coordination and support parameters. Variation of walking speed was significantly increased in Ndufs4(-/-) mice, suggesting hampered and uncoordinated gait. Furthermore, decreased regularity index, increased base of support and changes in support were noted in the Ndufs4(-/-) mice. Here, we report the ability of the CatWalk system to sensitively assess gait abnormalities in Ndufs4(-/-) mice. This objective gait analysis can be of great value for intervention and drug efficacy studies in animal models for mitochondrial disease. PMID- 26363426 TI - Recurrent Lower-Extremity Compartment Syndrome after Four-Compartment Fasciotomy Secondary to Acute Limb Ischemia. AB - Lower-extremity compartment syndrome is a limb-threatening event necessitating emergent treatment using fasciotomy. Recurrent compartment syndrome is rare and has only been reported after trauma and in conjunction with underlying connective tissue disorders. In this report, we present a case of recurrent lower-extremity compartment syndrome caused by ischemia-reperfusion injury, in a patient previously treated with adequate 4-compartment fasciotomies. As such, this is the first reported case of recurrent compartment syndrome in the setting of ischemia reperfusion injury that required treatment with 4-compartment fasciotomies on both occasions. This case demonstrates that fasciotomy is not protective against the development of recurrent compartment syndrome due to ischemia-reperfusion injury and that patients at high risk require monitoring. PMID- 26363427 TI - Mycotic Aneurysm of the Common Carotid Artery as a Presenting Symptom for Early Colorectal Malignancy. AB - Mycotic carotid aneurysms are rare vascular conditions that are associated with high mortality if left untreated. We present a gentleman who had a progressively enlarging tender pulsatile swelling on the right side of neck. Emergency computed tomography scan showed a large mycotic aneurysm arising from the right common carotid artery, and he underwent emergency open exploration with interposition bypass graft. Bacteroides fragilis species, which signified gastrointestinal related sepsis, was isolated from the thrombus culture. Subsequently search of systemic septic source showed an early rectal adenocarcinoma. This is the first case in the world's literature of a patient who had B. fragilis mycotic carotid aneurysm as a presenting complaint of his occult rectal malignancy. PMID- 26363425 TI - Association of change in brain structure to objectively measured physical activity and sedentary behavior in older adults: Age, Gene/Environment Susceptibility-Reykjavik Study. AB - Many studies have examined the hypothesis that greater participation in physical activity (PA) is associated with less brain atrophy. Here we examine, in a sub sample (n=352, mean age 79.1 years) of the Age, Gene/Environment Susceptibility Reykjavik Study cohort, the association of the baseline and 5-year change in magnetic resonance imaging (MRI)-derived volumes of gray matter (GM) and white matter (WM) to active and sedentary behavior (SB) measured at the end of the 5 year period by a hip-worn accelerometer for seven consecutive days. More GM (beta=0.11; p=0.044) and WM (beta=0.11; p=0.030) at baseline was associated with more total physical activity (TPA). Also, when adjusting for baseline values, the 5-year change in GM (beta=0.14; p=0.0037) and WM (beta=0.11; p=0.030) was associated with TPA. The 5-year change in WM was associated with SB (beta=-0.11; p=0.0007). These data suggest that objectively measured PA and SB late in life are associated with current and prior cross-sectional measures of brain atrophy, and that change over time is associated with PA and SB in expected directions. PMID- 26363428 TI - Endovascular Treatment of 2 True Degenerative Aneurysms of Superficial Femoral Arteries. AB - We report the rare observation of a 58-year-old patient presenting 2 degenerative aneurysms of the superficial femoral arteries, with a rupture of the right aneurysm, treated by covered stents, with a satisfying midterm follow-up. The endovascular approach is a minimally invasive procedure which should be proposed as the first-line treatment to all the patients presenting aneurysms of the superficial femoral arteries, both asymptomatic as complicated. PMID- 26363429 TI - Emergency contraception: A multispecialty survey of clinician knowledge and practices. AB - OBJECTIVES: To assess knowledge and provision of emergency contraception (EC), particularly the most effective methods. STUDY DESIGN: A web-based survey was distributed to a cross-sectional convenience sample of healthcare providers across specialties treating reproductive-aged women. The survey was sent to 3260 practicing physicians and advanced practice clinicians in 14 academic centers between February 2013 and April 2014. We analyzed responses by provider specialty using multivariable logistic regression. RESULTS: The final sample included 1684 providers (response rate=51.7%). Ninety-five percent of the respondents had heard of levonorgestrel (LNG) EC. Among reproductive health specialists, 81% provide LNG EC in their practice, although only half (52%) had heard of ulipristal acetate (UPA) and very few provide it (14%). The majority in family medicine (69%) and emergency medicine (74%) provide LNG, in contrast to 42% of internists and 55% of pediatricians. However, the more effective methods [UPA and copper intrauterine device (IUD)] were little known and rarely provided outside of reproductive health specialties; 18% of internists and 14% of emergency medicine providers had heard of UPA and 4% provide it. Only 22% of emergency providers and 32% of pediatricians had heard of the copper IUD used as EC. Among reproductive health specialists, only 36% provide copper IUD as EC in their practice. Specialty, provider type and proportion of women of reproductive age in the practice were related to knowledge and provision of some forms of EC. CONCLUSIONS: Awareness and provision of the most effective EC methods, UPA and the copper IUD (which are provider dependent), are substantially lower than for LNG EC, especially among providers who do not focus on reproductive health. IMPLICATIONS: In our sample of 1684 healthcare providers from diverse specialties who treat reproductive-aged women, knowledge and provision of the most effective forms of EC (UPA and the copper IUD) are far lower than for LNG EC. Women should be offered the full range of EC methods. PMID- 26363430 TI - Controlled release of copper from an intrauterine device using a biodegradable polymer. AB - BACKGROUND: The adverse effects of copper intrauterine devices (IUDs) such as abnormal bleeding, pain and cramps may be due in part to the burst release of copper ions during the first few months of usage. This study focuses on controlling the initial burst release of copper ions. STUDY DESIGN: This study evaluated in vitro release rates of copper for a period of 1 year from standard CuT380 IUDs (n=6) and from CuT380 IUDs coated with poly(dl-lactide-co-glycolide) (PLGA) films (n=6). This study characterized the coated device for its morphological changes during degradation of film by scanning electron microscopy (SEM). RESULTS: CuT380 IUDs coated with PLGA film with a thickness of 0.10+/-0.02 mm showed a reduced initial copper release (40-80 mcg/day) compared with uncoated CuT380 IUDs (150-200 mcg/day). Statistically significant (p<.05) results were obtained at different time intervals during the overall study period of 1 year. SEM images showed degradation of coating. CONCLUSION: Coating a CuT380 IUD with biodegradable polymer reduced the initial copper release without affecting release at 1 year. Clinical trials are required to determine whether this could reduce side effects such as bleeding and pain associated with copper containing IUDs. PMID- 26363431 TI - Ectopic pregnancy with use of progestin-only injectables and contraceptive implants: a systematic review. AB - BACKGROUND: Use of contraception lowers a woman's risk of experiencing an ectopic pregnancy. In the case of method failure, however, progestin-only contraceptives may be more likely to result in ectopic pregnancies than some other methods such as combined hormonal and barrier contraceptives. OBJECTIVE: To describe ectopic pregnancy risk associated with use of implants and progestin-only injectable contraceptives through a systematic review of published studies. DATA SOURCES: We searched electronic databases for articles in any language published through May 2015 describing studies of progestin-only injectables and implants. We also searched bibliographies and review articles for additional studies. STUDY SELECTION AND EXTRACTION: Studies that reported any pregnancies were included in the review. Independent data extraction was performed by two authors based on predefined data fields, and where possible, we calculated the proportion of pregnancies that were ectopic and the ectopic pregnancy incidence rate per 1000 woman-years. RESULTS: Fifty-three studies of implants and 28 studies of injectables were identified; 79% reported pregnancy location. The proportion of ectopic pregnancy ranged from 0 to 100% with an incidence of 0-2.9 per 1000 woman years in studies of marketed levonorgestrel implants. Studies of etonogestrel implants and the injectables, depot-medroxyprogesterone acetate and norethisterone enanthate, reported few ectopic pregnancies. CONCLUSION: Progestin only contraceptive implants and injectables protect against ectopic pregnancy by being highly effective in preventing pregnancy overall; however, the absolute risk of ectopic pregnancy varies by type of progestin. Risk of ectopic pregnancy should not be a deterrent for use or provision of these methods. PMID- 26363432 TI - Using a dyadic logistic multilevel model to analyze couple data. AB - There is growing recognition within the sexual and reproductive health field of the importance of incorporating both partners' perspectives when examining sexual and reproductive health behaviors. Yet, the analytical approaches to address couple data have not been readily integrated and utilized within the demographic and public health literature. This paper seeks to provide readers unfamiliar with analytical approaches to couple data an applied example of the use of dyadic logistic multilevel modeling, a useful approach to analyzing couple data to assess the individual, partner and couple characteristics that are related to individuals' reproductively relevant beliefs, attitudes and behaviors. The use of multilevel models in reproductive health research can help researchers develop a more comprehensive picture of the way in which individuals' reproductive health outcomes are situated in a larger relationship and cultural context. PMID- 26363434 TI - Withdrawal as pregnancy prevention and associated risk factors among US high school students: findings from the 2011 National Youth Risk Behavior Survey. AB - PURPOSE: Withdrawal is less effective for preventing pregnancy than other contraceptive methods and offers no protection against sexually transmitted infections including HIV. Little is known from a national perspective about adolescents who primarily use withdrawal. This study describes the prevalence of withdrawal as their primary method of pregnancy prevention at last sexual intercourse among sexually active US high school students and associations with sexual risk and substance use. METHODS: Data from the 2011 National Youth Risk Behavior Survey were used to estimate sexually active students' most recent contraceptive method. Logistic regressions examined sexual behaviors and substance use, comparing students who used withdrawal to those who used no method, a condom and a highly effective method. RESULTS: Among 4793 currently sexually active students, 10.2% used withdrawal only, 12.4% used no method, 53.6% used a condom and 23.8% used a more effective method as their primary form of pregnancy prevention during last sexual intercourse. Students who used withdrawal were less likely than those who used no method to have had sexual intercourse before age 13 years (Adjusted Prevalence Ratio (APR) =.56) and currently use cocaine (APR=.36). Among females, students who used withdrawal were more likely to engage in risky behaviors than those who used a condom and those who used a highly effective method of pregnancy prevention in a number of ways (e.g., having multiple sex partners during the past 3 months, current alcohol use, binge drinking, current marijuana use, drank alcohol or used drugs before last sexual intercourse). CONCLUSIONS: Approximately 1 in 10 sexually active students used withdrawal only, about the same percentage as those who used no method. Health care providers and others who serve adolescents may want to discuss its pros and cons with their clients and help ensure that they have information about and access to other contraceptive methods that are more effective at preventing pregnancy and sexually transmitted infections. Health care professionals should not consider young people who use withdrawal similar in risk to those that use no method. PMID- 26363435 TI - Circulating CD34-positive cells, glomerular filtration rate and triglycerides in relation to hypertension. AB - OBJECTIVE: Serum triglycerides have been reported to be independently associated with the development of chronic kidney disease (CKD), which is known to play a role in vascular disturbance. On the other hand, circulating CD34-positve cells, including endothelial progenitor cells, are reported to contribute to vascular repair. However, no studies have reported on the correlation between triglycerides and the number of CD34-positive cells. Since hypertension is well known factor for vascular impairment, the degree of correlation between serum triglycerides and circulating CD34-positve cells should account for hypertension status. METHODS: We conducted a cross-sectional study of 274 elderly Japanese men aged >= 60 years (range 60-79 years) undergoing general health checkups. RESULTS: Multiple linear regression analysis of non-hypertensive subjects adjusting for classical cardiovascular risk factors showed that although triglyceride levels (1SD increments; 64 mg/dL) did not significantly correlate with glomerular filtration rate (GFR) (beta = -2.06, p = 0.163), a significant positive correlation was seen between triglycerides and the number of circulating CD34 positive cells (beta = 0.50, p = 0.004). In hypertensive subjects, a significant inverse correlation between triglycerides and GFR was observed (beta = -2.66, p = 0.035), whereas no significant correlation between triglycerides and the number of circulating CD34-positive cells was noted (beta = -0.004, p = 0.974). CONCLUSION: Since endothelial progenitor cells (CD34-positive cells) have been reported to contribute to vascular repair, our results indicate that in non hypertensive subjects, triglycerides may stimulate an increase in circulating CD34-positive cells (vascular repair) by inducing vascular disturbance. PMID- 26363433 TI - A randomized controlled trial of daily text messages versus monthly paper diaries to collect bleeding data after intrauterine device insertion. AB - OBJECTIVE: Bleeding data in contraceptive trials are often collected using daily diaries, but data quality may vary due to compliance and recall bias. Text messaging is a widespread and promising modality for data collection. STUDY DESIGN: This trial randomized participants 1:1 to use text messages or paper diaries to report on bleeding experienced during the 90 days after intrauterine device (IUD) insertion. Participants chose either the copper T380A or the 52-mg levonorgestrel IUD. Our primary outcome was number of days of reported bleeding data. We hypothesized that data gathered with daily text messages would have fewer missing values than paper diaries. Intention to treat analyses used the rank-sum test to compare medians. RESULTS: Two hundred thirty women enrolled, and randomization yielded groups similar in baseline characteristics. Twenty percent of participants provided no bleeding data; of these, 77% were assigned to paper diaries. With 90 days of reporting, approximately 20% in each group provided complete bleeding data. The text group reported a median of 82 days [interquartile range (IQR) 40-89] and the paper group reported a median of 36 days (IQR 0-88) (p<=.001). The number of responses received decreased gradually over the 90-day period but was always higher in the text group. Women who had attained higher levels of education did well regardless of data collection modality, while response rates of text messages were greater among those with a high school education or less (p<.01). CONCLUSIONS: Participants reporting bleeding via text messages provided more complete data than women using paper diaries. IMPLICATIONS: Depending on resources and population of interest, text messages may be a useful modality to improve data collection for patient-reported outcomes. PMID- 26363436 TI - Natural human apoA-I mutations L141RPisa and L159RFIN alter HDL structure and functionality and promote atherosclerosis development in mice. AB - OBJECTIVE: Mutations in human apolipoprotein A-I (apoA-I) are associated with low high-density lipoprotein (HDL) cholesterol levels and pathological conditions such as premature atherosclerosis and amyloidosis. In this study we functionally characterized two natural human apoA-I mutations, L141RPisa and L159RFIN, in vivo. METHODS: We generated transgenic mice expressing either wild-type (WT) or the two mutant forms of human apoA-I on a mouse apoA-I(-/-) background and analyzed for abnormalities in their lipid and lipoprotein profiles. HDL structure and functionality, as well as atherosclerosis development following a 14-week high-fat diet were assessed in these mice. RESULTS: The expression of either apoA I mutant was associated with markedly reduced serum apoA-I (<10% of WT apoA-I), total and HDL-cholesterol levels (~20% and ~7% of WT apoA-I, respectively) and the formation of few small size HDL particles with prebeta2 and alpha3, alpha4 electrophoretic mobility. HDL particles containing either of the two apoA-I mutants exhibited attenuated anti-oxidative properties as indicated by their inability to prevent low-density lipoprotein oxidation, and by decreased activities of paraoxonase-1 and platelet-activating factor acetylhydrolase. However, the apoA-I(L141R)Pisa or apoA-I(L159R)FIN-containing HDL particles demonstrated increased capacity to promote ATP-Binding Cassette Transporter A1 mediated cholesterol efflux from macrophages. Expression of apoA-I(L141R)Pisa or apoA-I(L159R)FIN mutations in mice was associated with increased diet-induced atherosclerosis compared to either WT apoA-I transgenic or apoA-I(-/-) mice. CONCLUSIONS: These findings suggest that natural apoA-I mutations L141RPisa and L159RFIN affect the biogenesis and the functionality of HDL in vivo and predispose to diet-induced atherosclerosis in the absence of any other genetic defect. PMID- 26363437 TI - Mediation analysis of the relationship between sex, cardiovascular risk factors and mortality from coronary heart disease: Findings from the population-based VHM&PP cohort. AB - BACKGROUND: In Europe, annually about 77,000 women, but 253,000 men die prematurely from coronary heart disease (CHD) before the age of 65 years. This gap narrows with increasing age and disappears after the eighth life decade. However, little is known regarding the contribution of cardiovascular risk factors to this sex difference. OBJECTIVE: We investigated to what extent men's higher risk of dying from CHD is explained through a different risk factor profile, as compared to women. METHODS: Mediation analysis technique was used to assess the specific contributions of blood pressure, cholesterol, glucose, and smoking to the difference between men and women regarding CHD mortality in a large Austrian cohort consisting of 117,264 individuals younger than 50 years (as a proxy for pre-menopausal status) and 54,998 older ones, with 3892 deaths due to CHD during a median follow-up of 14.6 years. RESULTS: Adjusting for age and year of examination, we observed a male versus female CHD mortality hazard ratio (HR) of 4.7 (95% CI: 3.4-5.9) in individuals younger than 50 years, of which 40.9% (95% CI: 27.1%-54.7%) was explained through risk factor pathways, mainly through blood pressure. In older participants, there was a HR of 1.9 (95% CI: 1.8-2.0) of which 8.2% (95% CI: 4.6%-11.7%) was mediated through the risk factors. CONCLUSION: The extent to which major risk factors contribute to the sex difference regarding CHD mortality decreases with age. The female survival advantage was explained to a substantial part through the pathways of major risk factors only in younger individuals. PMID- 26363438 TI - A Mediterranean diet and risk of myocardial infarction, heart failure and stroke: A population-based cohort study. AB - BACKGROUND AND AIMS: The Mediterranean diet, which is palatable and easily achievable, has been associated with lower all-cause and cardiovascular disease (CVD) incidence and mortality. Data on heart failure (HF) and stroke types are lacking. The aim was to examine a Mediterranean diet in relation to incidence of myocardial infarction (MI), HF and stroke types in a Swedish prospective cohort. METHODS: In a population-based cohort of 32,921 women, diet was assessed through a self-administered questionnaire. The modified Mediterranean diet (mMED) score was created based on high consumption of vegetables, fruits, legumes, nuts, whole grains, fermented dairy products, fish and monounsaturated fat, moderate intakes of alcohol and low consumption of red meat, on a 0-8 scale. Relative risks (RR) with 95% confidence intervals (CI), adjusted for potential confounders, were estimated by Cox proportional hazards regression models. RESULTS: During 10 y of follow-up (1998-2008), 1109 MIs, 1648 HFs, 1270 ischemic strokes and 262 total hemorrhagic strokes were ascertained. A high adherence to the mMED score (6-8), compared to low, was associated with a lower risk of MI (RR: 0.74, 95% CI: 0.61 0.90, p = 0.003), HF (RR: 0.79, 95% CI: 0.68-0.93, p = 0.004) and ischemic stroke (RR: 0.78, 95% CI: 0.65-0.93, p = 0.007), but not hemorrhagic stroke (RR: 0.88, 95% CI: 0.61-1.29, p = 0.53). CONCLUSIONS: Better adherence to a Mediterranean diet was associated with lower risk of MI, HF and ischemic stroke. The Mediterranean diet is most likely to be beneficial in primary prevention of all major types of atherosclerosis-related CVD. PMID- 26363439 TI - Evaluation of gunshot residue (GSR) evidence: Surveys of prevalence of GSR on clothing and frequency of residue types. AB - The evaluative approach is a logical approach to interpreting scientific findings in criminal cases, applying knowledge regarding the transfer, persistence and recovery of particulate material. The application of this approach to interpreting the finding of gunshot residue on the clothing of a suspect requires knowledge of background levels of GSR on clothing and on the frequency of different residue types in a particular environment. The cuffs of 100 upper outer garments submitted to a forensic laboratory in connection with non-firearms offences were sampled for gunshot residue. No 3-component lead/antimony/barium particles were found on 98 of them. Two 3-component particles were found on one of them and one 3-component particle was found on another. The frequency of occurrence of various particle types regarded as consistent with GSR was also explored. The findings show that, while 3-component particles were somewhat more likely to be encountered by chance on clothing than on hands, they are still relatively uncommon events. To investigate the frequency of occurrence of particular residue types, 100 discharged rounds of ammunition recovered at crime scenes were sampled and the types of residue present were determined. The results show that some residue types are significantly more common than others. Both sets of data will be of value in evaluating the significance of finding GSR on clothing of suspects in criminal cases. PMID- 26363440 TI - Development of a comprehensive spectral library of sildenafil and related active analogues using LC-QTOF-MS and its application for screening counterfeit pharmaceuticals. AB - The abuse or misuse of forged erectile-dysfunction drugs, containing phosphodiesterase type 5 inhibitors (e.g. sildenafil), is a serious issue globally. Therefore, the detection of sildenafil and related active analogues in counterfeit pharmaceuticals or the differentiation between counterfeit and authentic drugs has been performed with a variety of analytical techniques. Recently, a liquid chromatography-hybrid quadrupole time-of-flight mass spectrometry (LC-QTOF-MS)-based in-house library, consisting of accurate mass ion fragmentation information and retention times, was effectively applied to screen a large number of compounds in field of forensic toxicology. However, a comprehensive LC-QTOF-MS spectral library of sildenafil and related active analogues has not yet been reported. In the present study, a spectral library of 40 compounds of sildenafil and related analogues was developed with accurate mass spectra and retention times using LC-QTOF-MS, and applied to screen nine marketed counterfeit products. The in-house library successfully identified sildenafil, dimethylsildenafil, hydroxyhomosildenafil, demethylhongdenafil, pseudovardenafil and vardenafil in the samples. Our LC-QTOF-MS-based spectral library search is considered a powerful approach for identifying sildenafil and related active analogues in counterfeit pharmaceuticals. PMID- 26363441 TI - The effect of common imaging and hot water maceration on DNA recovery from skeletal remains. AB - Identifying human remains often begins with cleaning and imaging the material. Hot water maceration is used to remove adherent soft tissue from bone and radiographs are taken to better visualize osseous details. Heat and radiation are known to have harmful effects on DNA, but their ability to degrade DNA when used for cleaning and imaging has not been well studied. To better understand their individual and combined effects on the recoverability of DNA from bone, skeletal samples were subjected to (1) hot water maceration (62 degrees C for 45 min); (2) CT scanning (0.6mm slices, 120 kV, 10.4s); (3) X-ray (50 kVp, 150 mA, 0.03 s, 40 in); and (4) all 3 treatments combined. Forty-eight DNA samples were extracted, quantified and amplified with the AmpFLSTR((r)) Identifiler((r)) system. Nearly all of the processed samples had reduced RFU values relative to the unprocessed samples, indicating some amount of genetic loss. This loss did not always translate into loss of profile completeness, since only a few samples had a reduction in the number of loci detected after processing. DNA yields were not significantly reduced by any one of the processing methods, however the results indicate that the damaging effects are additive. It is possible that processing may reduce a bone's DNA reservoir and as more procedures are preformed, the pool of available genetic information might be diminished. Many intrinsic and extrinsic factors can affect the recoverability of DNA from bone. Collecting a DNA sample prior to processing avoids the negative effects from hot water maceration and radiological imaging. PMID- 26363442 TI - A randomized controlled 27 years follow up of three resin composites in Class II restorations. AB - OBJECTIVE: To evaluate the durability of three conventional resin composites in Class II restorations during 27 years. METHODS: Thirty participants, 25 female and 5 male (mean age 38.2 years, range 25-63), received at least three (one set) as similar as possible Class II restorations of moderate size. The three cavities were chosen at random to be restored with a chemical-cured (Clearfil Posterior) and two visible light-cured resin composites (Adaptic II, Occlusin). A chemical cured enamel bonding agent (Clearfil New Bond) was applied after Ca(OH)2 covering of dentin and enamel etch. Marginal sealing of the restorations was performed after finishing. One operator placed 99 restorations (33 sets). Evaluation was performed with slightly modified USPHS criteria at baseline, 2, 3, 10 and 27 years. RESULTS: Postoperative sensitivity was observed in 5 patients. Three participants with 11 restorations (11%) could not be evaluated at the 27 year recall. Thirty-seven restorations failed (13 AII, 10 CP and 14 O). The overall success rate after 27 years was 56.5% (AII 55.2%, CP 63.0%, O 51.7%; p=0.70), with an annual failure rate of 1.6%. The main reason for failure was secondary caries (54.1%), followed by occlusal wear (21.6%) and material fracture (18.9%). Non-acceptable color match was seen in 24 (28.3%) of the restorations (AII 2, CP 16, O 6). Cox regression-analysis showed significant influence of the covariates tooth type, caries risk, and bruxing activity of the participants. CONCLUSIONS: Class II restorations of the three conventional resin composites showed an acceptable success rate during the 27 year evaluation. PMID- 26363443 TI - Tolerability and Clinical Activity of Post-Transplantation Azacitidine in Patients Allografted for Acute Myeloid Leukemia Treated on the RICAZA Trial. AB - Disease relapse is the major causes of treatment failure after allogeneic stem cell transplantation (SCT) in patients with acute myeloid leukemia (AML). As well as demonstrating significant clinical activity in AML, azacitidine (AZA) upregulates putative tumor antigens, inducing a CD8(+) T cell response with the potential to augment a graft-versus-leukemia effect. We, therefore, studied the feasibility and clinical sequelae of the administration of AZA during the first year after transplantation in 51 patients with AML undergoing allogeneic SCT. Fourteen patients did not commence AZA either because of transplantation complications or withdrawal of consent. Thirty-seven patients commenced AZA at a median of 54 days (range, 40 to 194 days) after transplantation, which was well tolerated in the majority of patients. Thirty-one patients completed 3 or more cycles of AZA. Sixteen patients relapsed at a median time of 8 months after transplantation. No patient developed extensive chronic graft-versus-host disease. The induction of a post-transplantation CD8(+) T cell response to 1 or more tumor-specific peptides was studied in 28 patients. Induction of a CD8(+) T cell response was associated with a reduced risk of disease relapse (hazard ratio [HR], .30; 95% confidence interval [CI], .10 to .85; P = .02) and improved relapse-free survival (HR, .29; 95% CI, .10 to .83; P = .02) taking into account death as a competing risk. In conclusion, AZA is well tolerated after transplantation and appears to have the capacity to reduce the relapse risk in patients who demonstrate a CD8(+) T cell response to tumor antigens. These observations require confirmation in a prospective clinical trial. PMID- 26363444 TI - Low Counts of B Cells, Natural Killer Cells, Monocytes, Dendritic Cells, Basophils, and Eosinophils are Associated with Postengraftment Infections after Allogeneic Hematopoietic Cell Transplantation. AB - Hematopoietic cell transplant (HCT) recipients are immunocompromised and thus predisposed to infections. We set out to determine the deficiency of which immune cell subset(s) may predispose to postengraftment infections. We determined day 28, 56, 84, and 180 blood counts of multiple immune cell subsets in 219 allogeneic transplant recipients conditioned with busulfan, fludarabine, and Thymoglobulin. Deficiency of a subset was considered to be associated with infections if the low subset count was significantly associated with subsequent high infection rate per multivariate analysis in both discovery and validation cohorts. Low counts of monocytes (total and inflammatory) and basophils, and low IgA levels were associated with viral infections. Low plasmacytoid dendritic cell (PDC) counts were associated with bacterial infections. Low inflammatory monocyte counts were associated with fungal infections. Low counts of total and naive B cells, total and CD56(high) natural killer (NK) cells, total and inflammatory monocytes, myeloid dendritic cells (MDCs), PDCs, basophils and eosinophils, and low levels of IgA were associated with any infections (due to any pathogen or presumed). In conclusion, deficiencies of B cells, NK cells, monocytes, MDCs, PDCs, basophils, eosinophils, and/or IgA plasma cells appear to predispose to postengraftment infections. PMID- 26363445 TI - In Memory of Mark D. Wood, Ph.D., Professor of Psychology (1960-2015). PMID- 26363446 TI - The Effectiveness of Message Framing and Temporal Context on College Student Alcohol Use and Problems: A Selective E-Mail Intervention. AB - AIMS: Only one study has examined message framing on college drinking, but did so in a laboratory setting among a general sample of college students. The current study was designed to: (a) compare the efficacy of emailed interventions differing by message framing and temporal context on alcohol involvement among heavy drinking college students and (b) examine need for cognition (NFC), consideration of future consequences (CFC) and self-efficacy as putative moderators. METHODS: Hazardous drinking college students (N = 220) were randomly assigned to conditions in a 2 (Frame: gain vs. loss) * 2 (Temporal Context: long term vs. short-term consequences) factorial design. Participants received four emails on heavy drinking consequences phrased in a manner consistent with their condition. After each message, participants were given a manipulation check. Participants were sent a 1-month follow-up assessment. Primary outcome measures were heavy episodic drinking (HED) and alcohol-related problems. We hypothesized two main effects (less alcohol consumption in the gain-frame and short-term condition), qualified by a Frame * Temporal Context interaction with substantially less alcohol involvement in the gain-frame/short-term condition. RESULTS: There was very little study attrition (96.4% completed follow-up survey, 93.2-99.5% completed manipulation checks), and strong effects were observed for the manipulations. A 2 * 2 ANCOVA, controlling for baseline alcohol involvement, revealed no consistent main effects or interactions on either outcome. No moderation was observed for any putative moderator. CONCLUSIONS: These results do not replicate prior laboratory-based research. The null findings may be attributed to the heavy drinking sample or electronic means of message delivery. PMID- 26363447 TI - Point-of-sale tobacco marketing in rural and urban Ohio: Could the new landscape of Tobacco products widen inequalities? AB - Considerable research has examined how cigarette point-of-sale advertising is closely related to smoking-related disparities across communities. Yet few studies have examined marketing of alternative tobacco products (e.g., e cigarettes). The goal of the present study was to examine external point-of-sale marketing of various tobacco products and determine its association with community-level demographics (population density, economic-disadvantage, race/ethnicity) in urban and rural regions of Ohio. During the summer of 2014, fieldworkers collected comprehensive tobacco marketing data from 199 stores in Ohio (99 in Appalachia, 100 in Columbus), including information on external features. The address of each store was geocoded to its census tract, providing information about the community in which the store was located. Results indicated that promotions for e-cigarettes and advertising for menthol cigarettes, cigarillos, and cigars were more prevalent in communities with a higher percentage of African Americans. Cigarillos advertising was more likely in high disadvantage and urban communities. A greater variety of products were also advertised outside retailers in urban, high-disadvantage, African American communities. Findings provide evidence of differential tobacco marketing at the external point-of-sale, which disproportionately targets urban, economically disadvantaged, and African American communities. There is a need for tobacco control policies that will help improve equity and reduce health disparities. PMID- 26363448 TI - FCGR2A, FCGR3A polymorphisms and therapeutic efficacy of anti-EGFR monoclonal antibody in metastatic colorectal cancer. AB - Anti-EGFR monoclonal antibodies (mAb) such as cetuximab, panitumumab are one kind of efficacious targeted drugs in treatment of metastatic colorectal cancer (mCRC). However, only a small proportion of patients harbored wild-KRAS genotype can benefit from it. We hypothesized that personal genetic heterogeneity might be the main cause leading to obvious difference in its clinical efficacy. A retrospective study including 82 mCRC patients treated with chemotherapy plus cetuximab and a comprehensive meta-analysis containing 2831 cases within sixteen eligible studies were conducted to investigate the possible association between FCGR2A H131R and FCGR3A V158F and clinical outcome of mCRC patients treated with anti-EGFR mAb based therapy. Results of the retrospective study showed that H131R within FCGR2A or V158F within FCGR3A were not associated with clinical outcome in 82 KRAS wild chemorefractory mCRC patients in co-dominant, dominant, recessive, over-dominant, allele genetic models. However, the comprehensive meta-analysis with the largest of sample size obtained the significant result between FCGR3A V158F and PFS (FV/VV vs. FF: Ph = 0.027, MSR = 0.680, 95%CI = 0.549-0.842 in overall population; Ph = 0.12, MSR = 0.728, 95%CI = 0.648-0.818 in KRAS wild population) and OS (VV vs. FF: Ph < 0.001, MSR = 0.733, 95%CI = 0.578-0.930 in overall population). These findings indicate that KRAS wild chemorefractory mCRC individual harbored genotype FF of V158Fcan benefit from anti-EGFR mAb adjuvant therapy in terms of PFS and OS, and it may be useful genetic biomarker to predict clinical survival of mCRC individuals with anti-EGFR mAb based therapy. PMID- 26363449 TI - The development of a new condom use expectancy scale for at-risk adults. AB - RATIONALE: Engaging in risky sexual behavior increases transmission of HIV. OBJECTIVE: The present study used previously elicited salient outcomes of condom use to examine the factor structure and test the predictive utility of a condom use expectancy scale. METHODS: Participants were drug offenders from court ordered drug diversion programs in Southern California. The condom use expectancy scale consisted of three factors: positive condom outcome items, negative condom outcome items, and safe sex items. RESULTS: The factor analysis confirmed the three-factor structure. Positive condom use expectancies were a significant predictor of both condom use and intentions to use condoms, and negative condom use expectancies predicted non-use of condoms. CONCLUSION: Understanding conditions of condom use can aid public health researchers and practitioners to better identify those in need of HIV prevention and how to target those needs. PMID- 26363450 TI - Towards an understanding of the relationship of functional literacy and numeracy to geographical health inequalities. AB - The relative contributions of functional literacy and functional numeracy to health disparities remain poorly understood in developed world contexts. We seek to unpack their distinctive contributions and to examine how these contributions are framed by place-based deprivation and rurality. We present a multilevel logistic analysis of the 2011 Skills for Life Survey (SfLS), a representative governmental survey of adults aged 16-65 in England. Outcome measures were self assessed health status and the presence of self-reported long-term health conditions. Exposure variables were functional literacy (FL) and functional numeracy (FN). Age, sex, individual socio-economic status, ethnicity, whether English was a first language, non-UK birthplaces, housing tenure and geography were included as potential confounders and mediators. Geography was measured as area-based deprivation and urban/rural status. FL and FN were both independently associated with self-assessed health status, though the association attenuated after taking account of confounders and mediators. For long-term conditions, the association with FN remained significant following inclusion of confounders and mediators whilst FL attenuated to non-significance. Rurality did not influence these associations. Area deprivation was a significant factor in attenuating the association between FL and self-assessed health status. Policy makers and health professionals will need to be aware of the distinctive impact of FN as well as FL when combating health inequalities, promoting health and managing long-term conditions. PMID- 26363451 TI - Impact of hospital delivery on child mortality: An analysis of adolescent mothers in Bangladesh. AB - New medical inventions for saving young lives are not enough if these do not reach the children and the mother. The present paper provides new evidence that institutional delivery can significantly lower child mortality risks, because it ensures effective and timely access to modern diagnostics and medical treatments to save lives. We exploit the exogenous variation in community's access to local health facilities (both traditional and modern) before and after the completion of the 'Women's Health Project' in 2005 (that enhanced emergency obstetric care in women friendly environment) to identify the causal effect of hospital delivery on various mortality rates among children. Our best estimates come from the parents fixed effects models that help limiting any parents-level omitted variable estimation bias. Using 2007 Bangladesh Demographic Health Survey data from about 6000 children born during 2002-2007, we show that, ceteris paribus, access to family welfare clinic particularly boosted hospital delivery likelihood, which in turn lowered neo-natal, early and infant mortality rates. The beneficial effect was particularly pronouncedamong adolescent mothers after the completion of Women's Health Project in 2005; infant mortality for this cohort was more than halved when delivery took place in a health facility. PMID- 26363452 TI - Sexually dimorphic expression of CREB binding protein in the green anole brain. AB - Green anoles are seasonally breeding lizards in which male sexual behavior is primarily regulated by an annual increase in testosterone. This hormone activates stereotyped behaviors, as well as morphological and biochemical changes in the brain, with greater effect in the breeding season than in the non-breeding season. This study is the first description of CREB binding protein (CBP) in the reptilian brain, and investigates the possibility that changes in CBP, an androgen receptor coactivator, may facilitate differences in responsiveness to testosterone across seasons. A portion of this gene was cloned for the green anole, and in situ hybridization was performed to examine the expression of CBP in the brains of gonadally intact male and female green anoles across breeding states. Additionally, hormonal regulation of CBP was evaluated across sex and season in animals that were gonadectomized and treated with testosterone or a control. Similar to other vertebrates, CBP was expressed at relatively high levels in steroid-sensitive brain regions. In the anole ventromedial amygdala, CBP mRNA levels were nearly twice as high in gonadally intact females compared to males. In contrast, CBP expression did not differ across seasons or hormone manipulation in this brain region. No significant effects were detected in the preoptic area or ventromedial hypothalamus. This pattern suggests that CBP might influence female-biased functions controlled by the ventromedial amygdala, but is not consistent with a role in mediating seasonal differences in responsiveness to testosterone in these areas associated with reproductive function. PMID- 26363453 TI - Autophagy inhibits endothelial progenitor cells migration via the regulation of MMP2, MMP9 and uPA under normoxia condition. AB - OBJECTIVE: The aim of this study was to explore the role of autophagy on the regulation of endothelial progenitor cells (EPCs) migration under normoxic condition. METHODS: After EPCs were isolated and characterized in vitro, we employed Atg5 knocking down and rapamycin to monitor the autophagy, and performed wound healing and transwell assay to assess the cell migration. On the mechanism, the expression of matrix metalloproteinases (MMPs) and urokinase type plasminogen activator (uPA) was evaluated. RESULTS: Atg5 knocking down and rapamycin could respectively inhibit and enhance autophagy, which could result in significantly increased and decreased cell migration in wound healing and transwell assay under normoxic condition. Moreover, Atg5 knocking down could significantly increase the expression of MMP2, MMP9 and uPA in EPCs while rapamycin could decrease the expression of uPA and MMP9. In addition, the mTOR-P70 S6K pathway was also involved in EPCs migration regulation. CONCLUSIONS: These results demonstrated that autophagy could regulate the EPCs migration through mTOR-P70 S6K pathway, and MMP2, MMP9 and uPA may also involve in the regulation mechanism. PMID- 26363454 TI - Protective effects of methane-rich saline on diabetic retinopathy via anti inflammation in a streptozotocin-induced diabetic rat model. AB - As the commonest complication of diabetes mellitus (DM), diabetic retinopathy (DR) is a neuro-vascular disease with chronic inflammatory. Methane could exert potential therapeutic interest in inflammatory pathologies in previous studies. Our study aims to evaluate the protective effects of methane-rich saline on DR and investigate the potential role of related MicroRNA (miRNA) in diabetic rats. Streptozotocin-induced diabetic Sprague-Dawley rats were injected intraperitoneally with methane-rich or normal saline (5 ml/kg) daily for eight weeks. Morphology changes and blood-retinal barrier (BRB) permeability were assessed by hematoxylin eosin staining and Evans blue leakage. Retinal inflammatory cytokines levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL1-beta) were evaluated by immunohistochemistry. Retinal protein expressions of glial fibrillary acidic protein (GFAP) and vascular endothelial growth factor (VEGF) were determined by western blotting. Retinal miRNA expressions were examined by miRNA-specific microarray, verified by quantitative RT-PCR and predicted by GO enrichment and KEGG pathway analysis. There was no significant changes in blood glucose level and body weight of diabetic rats with methane-rich or normal saline treatment, but the decreased retinal thickness, retinal ganglial cell loss and BRB breakdown were all significantly suppressed by methane treatment. DM-induced retinal overexpressions of TNF-alpha, IL-1beta, GFAP and VEGF were also significantly ameliorated. Moreover, the methane treatment significantly up-regulated retinal levels of miR 192-5p (related to apoptosis and tyrosine kinase signaling pathway) and miR-335 (related to proliferation, oxidative stress and leukocyte). Methane exerts protective effect on DR via anti-inflammation, which may be related to the regulatory mechanism of miRNAs. PMID- 26363455 TI - TIA-1 and TIAR interact with 5'-UTR of enterovirus 71 genome and facilitate viral replication. AB - Enterovirus 71 is one of the major causative pathogens of HFMD in children. Upon infection, the viral RNA is translated in an IRES-dependent manner and requires several host factors for effective replication. Here, we found that T-cell restricted intracellular antigen 1 (TIA-1), and TIA-1 related protein (TIAR) were translocated from nucleus to cytoplasm after EV71 infection and localized to the sites of viral replication. We found that TIA-1 and TIAR can facilitate EV71 replication by enhancing the viral genome synthesis in host cells. We demonstrated that both proteins bound to the stem-loop I of 5'-UTR of viral genome and improved the stability of viral genomic RNA. Our results suggest that TIA-1 and TIAR are two new host factors that interact with 5-UTR of EV71 genome and positively regulate viral replication. PMID- 26363456 TI - High glucose and interleukin 1beta-induced apoptosis in human umbilical vein endothelial cells involves in down-regulation of monocarboxylate transporter 4. AB - Hyperglycaemia and inflammatory can induce apoptosis in vascular endothelial cells, which contributes to the development of vascular complications in diabetes. Endothelial cells depend on glycolysis for their energy metabolism, and monocarboxylate transporters (MCTs) regulate intracellular pH by mediating the influx and efflux of lactate. Here, we evaluate the role of MCT4 in high glucose (HG) and interleukin 1beta (IL-1beta)-induced apoptosis in human umbilical vein endothelial cells (HUVECs). We demonstrate that aortic endothelium damage is severe in db/db mice by using scanning ion conductance microscopy (SICM). HG and IL-1beta decrease MCT4 and its location on plasma membrane, as well as increase lactic acid accumulation and apoptosis in HUVECs. Knockdown of MCT4 blocks lactate efflux to result in lactic acid accumulation and pH dropping, which is involved in triggering apoptosis in HUVECs. PMID- 26363457 TI - Two inhibitory systems and CKIs regulate cell cycle exit of mammalian cardiomyocytes after birth. AB - Mammalian cardiomyocytes actively proliferate during embryonic stages, following which they exit their cell cycle after birth, and the exit is maintained. Previously, we showed that two inhibitory systems (the G1-phase inhibitory system: repression of cyclin D1 expression; the M-phase inhibitory system: inhibition of CDK1 activation) maintain the cell cycle exit of mouse adult cardiomyocytes. We also showed that two CDK inhibitors (CKIs), p21(Cip1) and p27(Kip1), regulate the cell cycle exit in a portion of postnatal cardiomyocytes. It remains unknown whether the two inhibitory systems are involved in the cell cycle exit of postnatal cardiomyocytes and whether p21(Cip1) and p27(Kip1) also inhibit entry to M-phase. Here, we showed that more than 40% of cardiomyocytes entered an additional cell cycle by induction of cyclin D1 expression at postnatal stages, but M-phase entry was inhibited in the majority of cardiomyocytes. Marked cell cycle progression and endoreplication were observed in cardiomyocytes of p21(Cip1) knockout mice at 4 weeks of age. In addition, tri- and tetranucleated cardiomyocytes increased significantly in p21(Cip1) knockout mice. These data showed that the G1-phase inhibitory system and two CKIs (p21(Cip1) and p27(Kip1)) inhibit entry to an additional cell cycle in postnatal cardiomyocytes, and that the M-phase inhibitory system and p21(Cip1) inhibit M phase entry of cardiomyocytes which have entered the additional cell cycle. PMID- 26363458 TI - Endoplasmic reticulum stress-mediated autophagy contributes to bluetongue virus infection via the PERK-eIF2alpha pathway. AB - Bluetongue virus (BTV) is an important pathogen of wild and domestic ruminants. We have previously reported that BTV1 infection induced autophagy for its own benefit, but how this occurs remains unclear. Here, the classical autophagy features including autophagsomes formation, GFP-LC3 dots and LC3-II conversation were shown in BTV1-infected cells, we also found the endoplasmic reticulum (ER) stress was triggered by BTV1 infection, which was demonstrated by the increased transcription level of the ER stress marker GRP78 and the expanded morphology of ER. During ER stress, PERK and eIF2alpha phosphorylation increased along with BTV1 infection, consistent with the elevated LC3 level, indicating that the PERK pathway of the unfolded protein response (UPR) was activated. In addition, both the blockage of PERK by GSK2656157 or knockdown of eIF2alpha by siRNA reduced the level of LC3, which suggested that the PERK-eIF2alpha pathway contributed to autophagy induced by BTV1. Furthermore, inactivation of PERK or silencing of eIF2alpha both significantly reduced the expression of VP2 protein and the viral yields in the supernatants. In sum, these data suggest that ER stress mediates autophagy via the PERK-eIF2alpha pathway and contributes to BTV1 replication, thus offering new insight into the molecular mechanisms of the BTV-host interaction. PMID- 26363459 TI - Functional requirement of tyrosine residue 429 within CD5 cytoplasmic domain for regulation of T cell activation and survival. AB - CD5 has been mainly described as a negative regulator of TCR and BCR signaling and recent evidence has shown an important role for this receptor in delivering pro-survival signals. However, the molecular mechanisms underlying these processes remain unresolved. TCR crosslinking leads to phosphorylation of three tyrosine residues within the cytoplasmic tail of CD5 (Y429, Y441 and Y463) leading to the recruitment of signaling molecules like PI3K, c-Cbl and RasGAP; nevertheless, the role of these residues in T cell survival has not yet been assessed. In this study, we show that alanine-scanning mutagenesis of such tyrosine residues, either singly or in combination, leads to an increased thymocyte cell death with or without alpha-CD3 stimulation. Remarkably, the T cell death observed with each individual tyrosine mutant was Caspase 3 independent. Furthermore, Y429 mutation resulted in a hyper-phosphorylation of ERK suggesting that this tyrosine residue regulates cell survival through down modulation of TCR signaling. Mutation of Y441 or Y463 did not induce hyper responsiveness to TCR activation, indicating that they promoted T-cell survival by a TCR signal-independent pathway. Our results show that three tyrosine-based domains within CD5 cytoplasmic tail promote T-cell survival through non overlapping mechanisms. This study also reveals that Y429 domain of CD5, previously described as a "pseudo ITAM", is functionally an ITIM domain in T cells. PMID- 26363460 TI - Comparisons of chewing rhythm, craniomandibular morphology, body mass and height between mothers and their biological daughters. AB - OBJECTIVE: To study and compare the relationships between mean chewing cycle duration, selected cephalometric variables representing mandibular length, face height, etc., measured in women and in their teenage or young-adult biological daughters. DESIGN: Daughters were recruited from local high schools and the University of Michigan School of Dentistry. Selection criteria included healthy females with full dentition, 1st molar occlusion, no active orthodontics, no medical conditions nor medication use that could interfere with normal masticatory motor function. Mothers had to be biologically related to their daughters. All data were obtained in the School of Dentistry. Measurements obtained from lateral cephalograms included: two "jaw length" measures, condylion gnathion and gonion-gnathion, and four measures of facial profile including lower anterior face height, and angles sella-nasion-A point (SNA), sella-nasion-B point (SNB) and A point-nasion-B point (ANB). Mean cycle duration was calculated from 60 continuous chewing cycles, where a cycle was defined as the time between two successive maximum jaw openings in the vertical dimension. Other variables included subject height and weight. Linear and logistic regression analyses were used to evaluate the mother-daughter relationships and to study the relationships between cephalometric variables and chewing cycle duration. RESULTS: Height, weight, Co-Gn and Go-Gn were significantly correlated between mother-daughter pairs; however, mean cycle duration was not (r(2)=0.015). Mean cycle duration was positively correlated with ANB and height in mothers, but negatively correlated with Co-Gn in daughters. CONCLUSIONS: Chewing rate is not correlated between mothers and daughters in humans. PMID- 26363461 TI - Association between polymorphism of MMP-1 promoter and the susceptibility to anterior disc displacement and temporomandibular joint osteoarthritis. AB - OBJECTIVE: To investigate the correlation of the polymorphism of MMP-1 promoter ( 1607 1G/2G) with the susceptibility to anterior disc displacement (ADD) and temporomandibular joint osteoarthritis (TMJ OA). METHODS: A total of 185 healthy individuals (group A), 141 unilateral ADDWR patients (group B), and 321 unilateral ADDWOR patients (group C) were included in the investigation. Group C included 115 patients without TMJ OA (named group C-1) and 206 with TMJ OA (named group C-2). The genotyping of this single nucleotide polymorphism was evaluated by high resolution melting assay. Pairwise comparison between the distributions of genotypes and alleles in these groups was conducted with a multivariate logistic regression model adjusted on the basis of possible covariates. RESULTS: A significant difference in the 2G2G genotype frequency was found among the different groups on the basis of three sets of comparisons (P(C-A)<0.0005; P(C1 B)=0.049; P(C2-B)=0.018). The susceptibility of 2G2G genotype carriers to ADDWOR with or without TMJ OA was considerably higher than that of other genotypes carriers (OR(C-A)=2.455; OR(C1-B)=1.849; OR(C2-B)=1.912). A significant difference in 1G2G genotype frequency was also observed on the basis of two sets of comparisons (P(C-A)<0.0005; P(C2-B)=0.041). The susceptibility of 1G2G genotype carriers to ADDWOR with or without TMJ OA was also considerably higher than that of other genotype carriers (OR(C-A)=2.641; OR(C2-B)=1.896). CONCLUSION: The -1607 1G/2G polymorphism of MMP-1 promoter may be related to the susceptibility to ADDWOR with or without TMJ OA. PMID- 26363462 TI - Calorimetric and spectroscopic investigations of the binding of metallated porphyrins to G-quadruplex DNA. AB - BACKGROUND: The human telomere contains tandem repeat of (TTAGG) capable of forming a higher order DNA structure known as G-quadruplex. Porphyrin molecules such as TMPyP4 bind and stabilize G-quadruplex structure. METHODS: Isothermal titration calorimetry (ITC), circular dichroism (CD), and mass spectroscopy (ESI/MS), were used to investigate the interactions between TMPyP4 and the Co(III), Ni(II), Cu(II), and Zn(II) complexes of TMPyP4 (e.g. Co(III)-TMPyP4) and a model human telomere G-quadruplex (hTel22) at or near physiologic ionic strength ([Na(+)] or [K(+)]~0.15M). RESULTS: The apo-TMPyP4, Ni(II)-TMPyP4, and Cu(II)-TMPyP4 all formed complexes having a saturation stoichiometry of 4:1, moles of ligand per mole of DNA. Binding of apo-TMPyP4, Ni(II)-TMPyP4, and Cu(II) TMPyP4 is described by a "four-independent-sites model". The two highest-affinity sites exhibit a K in the range of 10(8) to 10(10)M(-1) with the two lower affinity sites exhibiting a K in the range of 10(4) to 10(5)M(-1). Binding of Co(III)-TMPyP4, and Zn(II)-TMPyP4, is best described by a "two-independent-sites model" in which only the end-stacking binding mode is observed with a K in the range of 10(4) to 10(5)M(-1). CONCLUSIONS: In the case of apo-TMPyP4, Ni(II) TMPyP4, and Cu(II)-TMPyP4, the thermodynamic signatures for the two binding modes are consistent with an "end stacking" mechanism for the higher affinity binding mode and an "intercalation" mechanism for the lower affinity binding mode. In the case of Co(III)-TMPyP4 and Zn(II)-TMPyP4, both the lower affinity for the "end stacking" mode and the loss of the intercalative mode for forming the 2:1 complexes with hTel22 are attributed to the preferred metal coordination geometry and the presence of axial ligands. GENERAL SIGNIFICANCE: The preferred coordination geometry around the metal center strongly influences the energetics of the interactions between the metallated-TMPyP4 and the model human telomeric G quadruplex. PMID- 26363463 TI - An invertebrate model for CNS drug discovery: Transcriptomic and functional analysis of a mammalian P-glycoprotein ortholog. AB - BACKGROUND: ABC efflux transporters at the blood brain barrier (BBB), namely the P-glycoprotein (P-gp), restrain the development of central nervous system (CNS) drugs. Consequently, early screening of CNS drug candidates is pivotal to identify those affected by efflux activity. Therefore, simple, high-throughput and predictive screening models are required. The grasshopper (locust) has been developed as an invertebrate in situ model for BBB permeability assessment, as it has shown similarities to vertebrate models. METHODS: Transcriptome profiling of ABC efflux transporters in the locust brain was performed. Subsequently, identified transcripts were matched with their counterparts in human, rat, mouse and Drosophila melanogaster, based on amino acid sequence similarity, and phylogenetic trees were constructed to reveal the most likely evolutionary history of the proteins. Further, functional characterization of a P-gp ortholog was achieved through transport studies, using a selective P-gp substrate and locust brain in situ, followed by kinetic analyses. RESULTS: A protein with high sequence similarity to the ABCB1 gene of vertebrates was found in the locust brain, which encodes P-gp in human and is considered the most vital efflux pump. Functionally, this model showed transport kinetic behaviors comparable to those obtained from in vitro models. Particularly, substrate affinity of the putative P gp was observed as in P-gp expressing cells lines, used for predicting drug penetration across biological barriers. CONCLUSION: Findings suggest a conserved mechanism of brain efflux activity between insects and vertebrates, confirming that this model holds promise for inexpensive and high-throughput screening relative to in vivo models, for CNS drug discovery. PMID- 26363464 TI - Engineering degrons of yeast ornithine decarboxylase as vehicles for efficient targeted protein degradation. AB - BACKGROUND: Ornithine decarboxylase (ODC), which catalyzes the first step of polyamine biosynthesis, undergoes rapid targeted degradation (TPD) with the help of its two degron sequences, namely the N-terminal 50 residues (N50) and alpha/beta domain (alpha/beta) housing antizyme binding element (AzBE), in response to increased polyamine levels. Antizyme binds to AzBE of ODC and delivers it to proteasome for degradation. Entire ODC was used as a tag to demonstrate TPD of chimeric proteins. METHODS: Here we fashioned three peptide sequences from yeast ODC to test their capability to act as degrons, namely N50, alpha/beta and Nalpha/beta (a combination of N50 and alpha/beta), and monitored their degradation potentials in chimeric proteins. We have examined the correlation between degradation potentials and structural integrity of the peptides, to find mechanistic explanations. RESULTS: Nalpha/beta with two signals in tandem is a better degron, under the regulation of antizyme. N50 like N44 reported earlier could drive chimeric proteins to degradation, while alpha/beta could not act as an independent degron. Strong correlation was observed between functional efficacy of the peptides and their structural integrity. N50, which was believed to be unstructured, displayed propensity for helical conformation. Nalpha/beta exhibited optimal structure, while alpha/beta failed to adopt native like conformation. CONCLUSIONS AND GENERAL SIGNIFICANCE: Functional efficacy of the degron Nalpha/beta is a consequence of its structural integrity. Nalpha/beta and N50 could target chimeric proteins to degradation. However, alpha/beta failed in the quest. Nalpha/beta, regulated by antizyme, is better suited than N50 for TPD to understand the function of novel proteins. PMID- 26363465 TI - Genome-Wide SNP Analysis of Southern African Populations Provides New Insights into the Dispersal of Bantu-Speaking Groups. AB - The expansion of Bantu-speaking agropastoralist populations had a great impact on the genetic, linguistic, and cultural variation of sub-Saharan Africa. It is generally accepted that Bantu languages originated in an area around the present border between Cameroon and Nigeria approximately 5,000 years ago, from where they spread South and East becoming the largest African linguistic branch. The demic consequences of this event are reflected in the relatively high genetic homogeneity observed across most of sub-Saharan Africa populations. In this work, we explored genome-wide single nucleotide polymorphism data from 28 populations to characterize the genetic components present in sub-Saharan African populations. Combining novel data from four Southern African populations with previously published results, we reject the hypothesis that the "non-Bantu" genetic component reported in South-Eastern Africa (Mozambique) reflects extensive gene flow between incoming agriculturalist and resident hunter-gatherer communities. We alternatively suggest that this novel component is the result of demographic dynamics associated with the Bantu dispersal. PMID- 26363467 TI - The Prognostic Impact of a Positive Vascular Margin on pT3 Clear Cell Renal Cell Carcinoma. AB - PURPOSE: We examined the impact of positive vascular margins in patients with pT3 clear cell renal cell carcinoma. MATERIALS AND METHODS: After excluding patients with nonvascular positive margins, metastasis, lymph node involvement, neoadjuvant therapy or nonclear cell histology, we identified 224 patients with venous tumor invasion through our institutional database from 1999 to 2013. Kaplan-Meier analysis and log rank tests were used to evaluate whether positive vascular margins were associated with progression-free survival or cancer specific survival. RESULTS: There were 41 patients (18%) with a positive vascular margin. Margin status was directly related to the level of invasion (p <0.0001). Compared to the negative vascular margin group the positive group had a significantly worse progression-free survival (p=0.01) but not cancer specific survival (p=0.3). Similarly the level of vascular thrombus invasion was significantly associated with worse progression-free survival (p=0.02) but not cancer specific survival (p=0.4). The 3-year progression-free survival was worst with inferior vena cava invasion and best with segmental/muscular venous branch invasion (54%, 95% CI 34-70 vs 76%, 95% CI 64-85). Among patients with only main renal vein thrombus, vascular margin status was not associated with progression free survival (p=0.5) or cancer specific survival (p=0.2). CONCLUSIONS: In patients with pT3N0/XM0 clear cell renal cell carcinoma positive vascular margins are associated with risk of disease progression. However, the risk of relapse associated with positive vascular margins is driven by the extent of vascular thrombus invasion. These findings suggest that the clinical significance of vascular margin status as currently defined in pT3 clear cell renal cell carcinoma is minimal. PMID- 26363468 TI - Construction of an MRI 3D high resolution sheep brain template. AB - Sheep is a developing animal model used in the field of neurosciences for the study of many behavioral, physiological or pathophysiological mechanisms, including for example, the central control of social behavior, brain injury or neurodegenerative diseases. However, sheep remains an orphan species in the field of magnetic resonance imaging (MRI). Therefore, a mean image (template), resulting of registrations of multiple subject images is needed and currently does not exist. In this study, we: i) computed multimodal high resolution 3D in vivo sheep brain templates of T1 weighted (T1W) and T2W images, ii) computed gray matter (GM), white matter (WM) and cerebrospinal fluid (CSF) prior probability maps using linear and optimized non-linear registrations iii) used prior probability maps to perform the segmentation of a single brain tissues. Computed multimodal sheep brain templates showed to preserve and underline all brain patterns of a single T1W or T2W image, and prior probability maps allowed to improve the segmentation of brain tissues. Finally, we demonstrated that these templates and prior probability maps were able to be portable in other publicly available imaging software and could be used as standardized spaces for multi institution neuroimaging studies or other neuroscience methods. PMID- 26363466 TI - Suppression of Nkx3.2 by phosphatidylinositol-3-kinase signaling regulates cartilage development by modulating chondrocyte hypertrophy. AB - Phosphatidylinositol-3-kinase (PI3K) is a key regulator of diverse biological processes including cell proliferation, migration, survival, and differentiation. While a role of PI3K in chondrocyte differentiation has been suggested, its precise mechanisms of action are poorly understood. Here we show that PI3K signaling can down-regulate Nkx3.2 at both mRNA and protein levels in various chondrocyte cultures in vitro. In addition, we have intriguingly found that p85beta, not p85alpha, is specifically employed as a regulatory subunit for PI3K mediated Nkx3.2 suppression. Furthermore, we found that regulation of Nkx3.2 by PI3K requires Rac1-PAK1, but not Akt, signaling downstream of PI3K. Finally, using embryonic limb bud cultures, ex vivo long bone cultures, and p85beta knockout mice, we demonstrated that PI3K-mediated suppression of Nkx3.2 in chondrocytes plays a role in the control of cartilage hypertrophy during skeletal development in vertebrates. PMID- 26363469 TI - Measurement of ketamine and xylazine in rat brain by liquid-liquid extraction and gas chromatography-mass spectrometry. AB - INTRODUCTION: In human and veterinary medicine, the injectable drugs ketamine and xylazine are mainly used in combination to induce, and then maintain general anaesthesia; they also provide pain and stress relief. Some side-effects have been reported on the auditory brainstem response, a method is therefore required to determine their concentrations in the brain. METHODS: This paper presents a method to determine nanogramme quantities of ketamine and xylazine in rat brain using liquid-liquid extraction and gas chromatography-mass spectrometry in selective ion monitoring mode. The technique requires only 0.5 g of sample, and uses xylazine d6 as an internal standard. RESULTS: The method was linear between 0.86 and 34.4 MUg/g of brain. Limits of quantification were 378 and 87 ng (approximately 0.76 and 0.17 MUg/g of brain) for ketamine and xylazine, respectively. The reliability of the method in terms of accuracy, within-day and between-day precision was also demonstrated. For xylazine, bias and intra-day precision were good (<3.0%), as was between-day precision (<10.5%); the equivalent values for ketamine were 7%, 11.1% and 20.9%, respectively. Stability of the analytes in the matrix at -80 degrees C was assessed over five months; both compounds were found to be stable for at least 1 month, even at very low concentrations. The procedure was successfully applied to determine (for the first time) the in vivo brain levels of both drugs in animals following systemic administration. DISCUSSION: The procedure will be useful in future studies of the side-effects of these drugs, and their interactions with other compounds. PMID- 26363470 TI - Spectral study of interaction between chondroitin sulfate and nanoparticles and its application in quantitative analysis. AB - In this work, the interaction between chondroitin sulfate (CS) and gold nanoparticles (GNPs) and silver nanoparticles (SNPs) was characterized for the first time. Plasma resonance scattering (PRS) and plasma resonance absorption (PRA) were used to investigate the characteristics of their spectrum. The results suggested that the CS with negative charge could interact with metal nanoparticles with negative charge and the adsorption of CS on the surface of SNPs was more regular than that of GNPs. The resonance scattering spectra also further confirmed the interaction between CS and SNPs. A new method for detection of CS based on the interaction was developed. CS concentrations in the range of 0.02-3.5 MUg/mL were proportional to the decreases of absorbance of SNPs. Compared with other reported methods, the proposed method is simple and workable without complex process, high consumption and expensive equipments. The developed method was applied to the determination of the CS contents from different biological origins and the results were compared with those obtained by the method of Chinese Pharmacopeia. The effects of matrix in plasma and other glycosaminoglycans on the determination of CS were also investigated. The results showed that a small quantity of blood plasma had no effect on the determination of CS and when the concentration ratio of CS to heparin was more than 10:1, the influence of heparin on the detection of CS could be ignored. This work gave a specific research direction for the detection of CS in the presence of metal nanoparticles. PMID- 26363471 TI - Binding of Cu(II) ions to peptides studied by fluorescence spectroscopy and isothermal titration calorimetry. AB - Steady-state and time-resolved fluorescence quenching measurements supported by Isothermal Titration Calorimetry (ITC) were used to study the interactions of Cu(2+) with four peptides. Two of them were taken from the N-terminal part of the FBP28 protein (formin binding protein) WW domain: Tyr-Lys-Thr-Ala-Asp-Gly-Lys-Thr Tyr-NH2 (D9) and its mutant Tyr-Lys-Thr-Ala-Asn-Gly-Lys-Thr-Tyr-NH2 (D9_M) as well as two mutated peptides from the B3 domain of the immunoglobulin binding protein G derived from Streptococcus: Asp-Val-Ala-Thr-Tyr-Thr-NH2 (J1) and Glu Val-Ala-Thr-Tyr-Thr-NH2 (J2). The measurements were carried out at 298.15K in 20mM 2-(N-morpholino)ethanesulfonic acid (MES) buffer solution with a pH of 6. The fluorescence of all peptides was quenched by Cu(2+) ions. The stoichiometry, conditional stability constants and thermodynamic parameters for the interactions of the Cu(2+) ions with D9 and D9_M were determined from the calorimetric data. The values of the conditional stability constants were additionally determined from fluorescence quenching measurements and compared with those obtained from calorimetric studies. There was a good correlation between data obtained from the two techniques. On the other hand, the studies revealed that J1 and J2 do not exhibit an affinity towards metal ions. The obtained results prove that fluorescence quenching experiments may be successfully used in order to determine stability constants of complexes with fluorescent ligands. Finally, based on the obtained results, the coordinating properties of the peptides towards the Cu(2+) ions are discussed. PMID- 26363472 TI - Globular adiponectin controls insulin-mediated vasoreactivity in muscle through AMPKalpha2. AB - Decreased tissue perfusion increases the risk of developing insulin resistance and cardiovascular disease in obesity, and decreased levels of globular adiponectin (gAdn) have been proposed to contribute to this risk. We hypothesized that gAdn controls insulin's vasoactive effects through AMP-activated protein kinase (AMPK), specifically its alpha2 subunit, and studied the mechanisms involved. In healthy volunteers, we found that decreased plasma gAdn levels in obese subjects associate with insulin resistance and reduced capillary perfusion during hyperinsulinemia. In cultured human microvascular endothelial cells (HMEC), gAdn increased AMPK activity. In isolated muscle resistance arteries gAdn uncovered insulin-induced vasodilation by selectively inhibiting insulin-induced activation of ERK1/2, and the AMPK inhibitor compound C as well as genetic deletion of AMPKalpha2 blunted insulin-induced vasodilation. In HMEC deletion of AMPKalpha2 abolished insulin-induced Ser(1177) phosphorylation of eNOS. In mice we confirmed that AMPKalpha2 deficiency decreases insulin sensitivity, and this was accompanied by decreased muscle microvascular blood volume during hyperinsulinemia in vivo. This impairment was accompanied by a decrease in arterial Ser(1177) phosphorylation of eNOS, which closely related to AMPK activity. In conclusion, globular adiponectin controls muscle perfusion during hyperinsulinemia through AMPKalpha2, which determines the balance between NO and ET-1 activity in muscle resistance arteries. Our findings provide a novel mechanism linking reduced gAdn-AMPK signaling to insulin resistance and impaired organ perfusion. PMID- 26363473 TI - Oxidative stress in chronic vascular disease: From prediction to prevention. AB - This review article is intended to describe the strong relationship between oxidative stress and vascular disease. Reactive oxygen species (ROS) play an important role in the pathogenesis of vascular disease: oxidative stress is intimately linked to atherosclerosis, through oxidation of LDL and endothelial dysfunction, to diabetes, mainly through advanced glycation end-products (AGEs)/receptor for AGE (RAGE) axis impairment, protein kinase C (PKC), aldose reductase (AR) and NADPH oxidase (NOX) dysfunction, and to hypertension, through renin-angiotensin system(RAS) dysfunction. Several oxidative stress biomarkers have been proposed to detect oxidative stress levels and to improve our current understanding of the mechanisms underlying vascular disease. These biomarkers include ROS-generating and quenching molecules, and ROS-modified compounds, such as F2-isoprostanes. An efficient therapeutic approach to vascular diseases cannot exclude evaluation and treatment of oxidative stress. In fact, oxidative stress represents an important target of several drugs and nutraceuticals, including antidiabetic agents, statins, renin-angiotensin system blockers, polyphenols and other antioxidants. A better understanding of the relations between atherosclerosis, diabetes, hypertension and ROS and the discovery of new oxidative stress targets will translate into consistent benefits for effective vascular disease treatment and prevention. PMID- 26363474 TI - Association is not causation! PMID- 26363475 TI - Efficacy of ultrasound-indicated cerclage in twin pregnancies, REPLAY. PMID- 26363476 TI - Potential harms outweigh benefits of indefinite monitoring of stable adnexal masses. AB - The management of women with asymptomatic adnexal masses should aim to balance potential benefit with potential harm. While masses with highly worrisome features or other signs of malignancy should be referred for surgery, the vast majority of masses have an indeterminate or benign appearance and are candidates for observation. Evidence supports the use of initial short-term serial ultrasound in distinguishing between benign and malignant masses. However, benefit from prolonged, potentially life-long monitoring of stable masses has not been demonstrated. Since the goal of monitoring an adnexal mass is to observe for worrisome growth or increasing complexity as an indicator of malignancy, if the mass remains stable, the likelihood of malignancy and therefore, the potential benefit of observation wanes with time. The recognition that Type 2 high grade serous cancers, which are responsible for the majority of deaths from ovarian cancer, arise from fallopian tube rather than ovarian precursors, further diminishes the likelihood that monitoring a stable ovarian mass will lead to early diagnosis of high grade disease. While some Type 1 cancers may develop from ovarian precursors, the available data suggest that any measurable benefit of monitoring known lesions for detection of these cancers is realized within the first year of observation. The argument in favor of indefinite, potentially life long monitoring of stable masses also fails to adequately account for the risks of perpetual imaging, which include the risk of incidental findings, an increased likelihood of unnecessary surgery, patient anxiety and cost. It is not always better to order a test than not order a test. Given the absence of evidence of benefit, observation of stable small adnexal masses should be limited in duration in order to minimize potential harms. PMID- 26363477 TI - Metroplasty to treat chronic pelvic pain resulting from outflow tract mullerian anomalies. AB - Chronic pelvic pain can result from noncommunicating uterine cavities in patients with mullerian anomalies. Traditional management has been to resect the noncommunicating uterine horn. Two cases are described. One had a unicornuate uterus with noncommunicating left uterine horn (American Fertility Society [AFS] classification IIb) and the other had a normal external uterine contour with noncommunicating left uterine cavity that did not fit any category of the AFS classification of mullerian anomalies. Attempts at connecting the noncommunicating cavities hysteroscopically failed in both cases. Successful unification of the cavities was subsequently achieved in the first case using the classic Strassman metroplasty with the assistance of the robot. The unification of uterine cavities was achieved using a modified Strassman metroplasty in the second patient, as there was no uterine horn for landmark. Robot assistance was utilized in this case as well. Both patients are symptom free after surgery. We conclude that laparoscopic Strassman metroplasty, with or without robot assistance, is a viable alternative to resection of uterine horns in patients with hematometra, chronic pelvic pain, and noncommunicating uterine cavities. PMID- 26363478 TI - Cerclage in twin pregnancies: we should wait before making definitive recommendations. PMID- 26363480 TI - Reply. PMID- 26363479 TI - Reply. PMID- 26363481 TI - Transvaginal cervical length scans to prevent prematurity in twins: a randomized controlled trial. AB - BACKGROUND: Twin pregnancies are associated with an increased risk of perinatal morbidity and mortality primarily due to spontaneous preterm deliveries. The mean gestational age for delivery is 35.3 weeks and twins account for 23% of preterm births <32 weeks. A number of strategies have been proposed to prevent preterm deliveries: tocolytics, bed rest, hospitalization, home uterine activity monitoring, cerclage, and most recently, progesterone. Unfortunately, none have proven effective. Recent metaanalyses and reviews suggest that transvaginal cervical length (TVCL) ultrasound in the second trimester is a powerful predictor of preterm birth among asymptomatic women. Indeed, TVCL has the highest positive and negative predictive values for determining the risk of spontaneous preterm delivery in twin pregnancies. It follows that TVCL assessment may allow identification of a subset of twin pregnancies that re better candidates for interventions intended to prevent prematurity. OBJECTIVE: We sought to determine whether use of TVCL prolongs gestation in twin pregnancies. STUDY DESIGN: This is a multicenter, randomized, controlled trial of 125 dichorionic or monochorionic/diamniotic twin pregnancies without prior preterm birth <28 weeks. The study group (n = 63) had TVCL and digital exams monthly from 16-28 weeks and were managed with a standard algorithm for activity restriction and cerclage. The control group (n = 62) had monthly digital cervical examinations but no routine TVCL ultrasound examinations. The primary outcome was gestational age at delivery. Secondary outcomes included percentage of deliveries <35 weeks, and maternal and neonatal outcomes. RESULTS: The mean gestational age at delivery was 35.7 weeks (95% confidence interval [CI], 35.2-36.2) among those managed with TVCL and 35.5 weeks (95% CI, 34.7-36.4) among the control patients. The Kaplan Meier estimates of deliveries <38 weeks were not significantly different between groups. This was true whether we compared curves with a log-rank test (P = .67), Breslow test (P = .67), or Tarone-Ware test (P = .64). The percentage of deliveries <35 0/7 weeks did not differ: 27.4% for subjects managed with routine TVCL and 28.6% for control subjects (relative risk, 0.96; 95% CI, 0.60-1.54). Our study had an 80% power to detect a 12-day difference in the gestational age at delivery with 95% confidence. CONCLUSION: The overall mean length of gestation and the percentage of women delivering <35 weeks did not differ between twin gestations managed with TVCL and digital exams monthly from 16-28 weeks with a standard algorithm for activity restriction and cerclage and controls who had monthly digital cervical examinations but no routine TVCL. Routine second trimester transvaginal ultrasound assessment of cervical length is not associated with improved outcomes when incorporated into the standard management of otherwise low-risk twin pregnancies. PMID- 26363482 TI - Efficacy of ultrasound-indicated cerclage in twin pregnancies: is evidence-based medicine always the right choice? PMID- 26363483 TI - Influence of race and ethnicity on in vitro fertilization outcomes: systematic review. AB - OBJECTIVE: We conducted a systematic review to evaluate the influence of race and ethnicity on clinical pregnancy and live birth outcomes after in vitro fertilization (IVF). STUDY: We searched PubMed, EMBASE, Web of Science, CINAHL, POPLINE, and Cochrane Central, and hand-searched relevant articles published through July 22, 2015. STUDY APPRAISAL AND SYNTHESIS METHODS: Two reviewers independently evaluated abstracts to identify studies that compared clinical pregnancy rates and live birth rates for >=2 racial and/or ethnic groups after nondonor IVF cycles. RESULTS: Twenty-four studies were included. All 5 US registry-based studies showed that black, Hispanic, and Asian women had lower clinical pregnancy rates and/or live birth rates after IVF, compared with white women. Similarly, most clinic-specific studies reported significant disparities in these primary outcomes, potentially attributable to differences in infertility diagnosis, spontaneous abortion, and obesity. Studies varied with respect to definitions of race/ethnicity, inclusion of first cycles vs multiple cycles for individual women, and collected covariates. Most studies were limited by sample size, inadequate adjustment for confounding, selection bias, and extensive missing data. CONCLUSIONS: Although current evidence points to race and ethnicity, especially black race, as strong predictors of poorer outcomes after IVF, the utility of results is constrained by the limitations described. PMID- 26363484 TI - Self-plagiarism: a misnomer. PMID- 26363485 TI - Are we stopping preterm birth trials too early? PMID- 26363486 TI - Expectant management in cholestasis in pregnancy. PMID- 26363487 TI - Trauma and Child Health: An Introduction to the Special Issue. AB - Potentially traumatic events are common occurrences that can lead to significant psychological distress, and yet, there has been remarkably little attention to the associations between traumatic events and youth's physical health. The articles contained in this Special Issue of the Journal of Pediatric Psychology represent a significant step forward in the establishment of "Trauma and Child Health" as a major area of study within the field of pediatric psychology. In this introductory article, we briefly describe several contextual issues that may help to set the stage for the articles contained in this Special Issue. These contextual issues include the most common types of traumatic events that are studied, as well as the features of traumatic events that may affect physical and mental health outcomes, such as whether casualties or interpersonal violence is involved. PMID- 26363488 TI - Relations Between Baseline and Nonlinear Longitudinal Changes in Children's Body Mass Index and Internalizing Symptoms. AB - OBJECTIVE: To determine whether initial body mass index for age (zBMI) and internalizing symptoms predict longitudinal changes in zBMI and internalizing symptoms-and the extent to which sex and race moderate these relations. METHODS: Participants included 12,674 (51% male) youth from the Early Childhood Longitudinal Study, Kindergarten Class 1998-1999. Data were collected in kindergarten, 1st, 3rd, 5th, and 8th grades. Teacher-reported internalizing symptoms were measured with the Social Rating Scale. RESULTS: Internalizing symptoms followed a quadratic growth trajectory, with initial low levels of symptoms that gradually increased over time and eventually leveled. zBMI followed a piecewise growth trajectory, with a transition in slope at 1st grade. Interactions emerged between zBMI and internalizing symptoms for White males. CONCLUSIONS: Associations between internalizing symptoms and BMI begin in early childhood for White males, and changes in zBMI are a function of the interactive effect of initial levels of internalizing difficulties and adiposity status. PMID- 26363489 TI - Simultaneous determination of triptolide, tripterifordin, celastrol and nine sesquiterpene alkaloids in Tripterygium preparations using high-performance liquid chromatography-triple quadrupole mass spectrometry. AB - Tripterygium wilfordii tablet (TWT) and Tripterygium hypoglaucum tablet (THT), the preparations of the two Tripterygium herbs, are well known for the treatment of rheumatoid arthritis and other related inflammatory diseases clinically. In the present study, a high performance liquid chromatography (HPLC) coupled with electrospray ionization (ESI) tandem triple quadrupole mass spectrometry (QQQ/MS) method was developed for simultaneous quantification of 12 chemical components in Tripterygium preparations. The fragmentation patterns of analytes using ESI and collision-induced dissociation (CID) techniques were reported. This assay method was validated with respect to linearity (r(2)>0.9991), precision, repeatability, and accuracy (recovery rate between 97.2 and 104.2%). The proposed method was successfully applied for simultaneous quantification of the 12 compounds in Tripterygium preparations from the different manufactures. In addition, to evaluate the quality of Tripterygium preparations, partial least square discrimination analysis (PLS-DA) was performed to differentiate the contents of 12 compounds. In conclusion, the established HPLC/QQQ/MS method was proven to be useful and efficient for quality control of Tripterygium preparations. PMID- 26363490 TI - Development and validation of an LC-MS/MS method for the determination of SB 505124 in rat plasma: Application to pharmacokinetic study. AB - A sensitive, selective and rapid liquid chromatography-electrospray ionization tandem mass spectrometry (LC-MS/MS) method has been developed for the quantification of the novel transforming growth factor-beta (TGF-beta) inhibitor SB-505124 in rat plasma and then validated. Plasma samples were prepared by simple protein precipitation. Separation was performed on a Diamonsil ODS chromatography column using a mobile phase of acetonitrile and 0.1% (v/v) aqueous formic acid. SB-505124 and the internal standard doxorubicin were detected in the positive ion mode using multiple reaction monitoring of the transitions at m/z 336.2->320.1 and 544.2->397.2, respectively. Calibration curve was linear (r>0.9996) over a concentration range of 10-5000 ng/mL with the lower quantification limit of 10 ng/mL. Both intra- and inter-day precision were within 6.5% and trueness were not more than 3.1%. Extraction recovery and matrix effect were within acceptable limits. Stability tests showed that SB-505124 and the IS remained stable throughout the analytical procedure. The validated LC-MS/MS method was then used to analyze the pharmacokinetics of SB-505124 administered to rats intravenously (8 mg/kg) or orally (10 mg/kg). Oral bioavailability of SB 505124 was calculated as 76.4%, indicating the potential of SB-505124 as an orally administered drug. PMID- 26363491 TI - Validated RP-HPLC and TLC-Densitometric Methods for Analysis of Ternary Mixture of Cetylpyridinium Chloride, Chlorocresol and Lidocaine in Oral Antiseptic Formulation. AB - This work was concerned with development, optimization, application and validation of reversed phase high performance liquid chromatography (RP-HPLC) and thin layer chromatography (TLC)-densitometric methods for analysis of cetylpyridinium chloride, chlorocresol and lidocaine in Canyon((r)) gel. The first developed RP-HPLC method depended on chromatographic separation on a ZORBAX Eclipse Plus C8 column, with elution with a mobile phase consisting of 0.05% phosphoric acid solution : acetonitrile : methanol (15 : 24 : 61, by volume), pumping the mobile phase at a flow rate of 1.00 mL min(-1), with ultraviolet detection at 220 nm. While in the subsequently developed method, the TLC densitometric method, complete separation of the studied mixture was achieved using methanol : acetone : acetic acid (7 : 3 : 0.2, by volume) as a mobile phase, aluminum plates precoated with silica gel 60 F254 as a stationary phase and 215 nm as the scanning wavelength. Factors affecting the developed methods were studied and optimized; moreover, methods had been validated as per the International Conference of Harmonization guideline and the results indicated that the suggested methods were reproducible, reliable and applicable for rapid routine analysis. Statistical comparison of the two developed methods with the reported HPLC ones using F- and Student's t tests showed no significant difference. PMID- 26363492 TI - Simultaneous Quantification of 11 Constituents in Wuji Pill Using Ultra Performance Liquid Chromatography Coupled With a Triple Quadrupole Electrospray Tandem Mass Spectrometry. AB - An ultra performance liquid chromatography coupled with a triple quadrupole electrospray tandem mass spectrometry (UPLC-MS-MS) method was developed for analyzing and identifying the constituents of 11 compounds including berberine, epiberberine, berberrubine, jatrorrhizine, coptisine, palmatine, evodiamine, rutaecarpine, limonin, paeoniflorin and albiflorin in Wuji pill (WJ pill), a traditional Chinese medicine. The chromatographic separation was performed on a C18 column and the mobile phase was composed of water (0.1% formic acid and 2 mmol ammonium acetate) and methanol with a linear gradient elution. The detection was performed by multiple reaction monitoring mode, using electrospray ionization in the positive ion mode. The total run time was 14 min. The calibration curves were linear with all correlation coefficients higher than 0.9987 in the tested range. The intra- and interday precisions were no more than 4.9%, and the average recoveries were from 92.4 to 107.8% with the relative standard deviations no more than 7.8%. The developed method was successfully employed to analyze five batches of WJ pill samples. This is the first time to establish a method for the quality control of WJ pill to ensure the safety and efficacy in clinical applications effectively. PMID- 26363493 TI - An immobilization-free electrochemical impedance biosensor based on duplex specific nuclease assisted target recycling for amplified detection of microRNA. AB - An immobilization-free electrochemical impedance biosensor for microRNA detection was developed in this work, which was based on both the duplex-specific nuclease assisted target recycling (DSNATR) and capture probes (Cps) enriched from the solution to electrode surface via magnetic beads (MBs). In the absence of miR-21, Cps cannot be hydrolyzed due to the low activity of duplex-specific nuclease (DSN) against ssDNA. Therefore, the intact Cps could be attached to the surface of magnetic glass carbon electrode (MGCE), resulting in a compact negatively charged layer as well as a large charge-transfer resistance. While in the presence of miR-21, it hybridized with Cp to form a DNA-RNA heteroduplex. Due to the considerable cleavage preference for DNA in DNA-RNA hybrids, DSN hydrolyzed the target-binding part of the Cp while liberating the intact miR-21 to hybridize with a new Cp and initiate the second cycle of hydrolysis. In this way, a single miR-21 was able to trigger the permanent hydrolysis of multiple Cps. Finally, all Cps were digested. Thus, the negatively charged layer could not be formed, resulting in a small charge-transfer resistance. By employing the above strategy, the proposed biosensor achieved ultrahigh sensitivity toward miR-21 with a detection limit of 60aM. Meanwhile, the method showed little cross-hybridization among the closely related miRNA family members even at the single-base-mismatched level. Successful attempts were made in applying the approach to detect miR-21 in human serum samples of breast cancer patients. PMID- 26363494 TI - Design of two electrode system for detection of antioxidant capacity with photoelectrochemical platform. AB - Recently, a flow photoelectrochemical cell has been first developed and applied to assay global antioxidant capacity in our group. Yet, shortcomings of liquid reference electrode such as sample contaminations from the leaking of the reference solution, mechanically fragile, temperature and light sensitivity, etc. are significant restrictions for integration and miniaturization of photoelectrochemical sensing instruments, which have greatly limited their practical applications. Bearing these problems, in this work a novel two electrode flow photoelectron-chemical system (two-EPCS) has been developed for detection of antioxidant capacity. It is noteworthy that the electrochemical modulation-free mode (detection at the potential of 0.0V) is performed, which has greatly simplified the analysis process and will result in significant simplifications of the instrument integrations. During the sample analysis, both standard antioxidants and commercial beverages were detected. Results evaluated from the two-EPCS are well agreed with those of the traditional three-EPCS at low potentials. By unloading of the reference electrode, it is of great convenience to design a novel photoelectrochemical microfluidic chip based on the two-EPCS, which has also been successfully applied for antioxidant capacity assay. It is satisfactory that comparable detection concentration range and sensitivity were accomplished by applying the microfluidic chip technique. Moreover, the two-EPCS is verified to be a universal platform which does not depend on selected optoelectronic materials but pervasive for general photocatalysts. Such a two EPCS should be considered as a feasible alternative to the three-EPCS, which will become a promising candidate for industrial and commercial photoelectrochemical sensing instrument integrations in the future. PMID- 26363495 TI - Depressive-like phenotype induced by AAV-mediated overexpression of human alpha synuclein in midbrain dopaminergic neurons. AB - Parkinson's disease (PD) is a neurodegenerative disorder characterized by a progressive loss of nigral dopaminergic neurons and by the presence of aggregates containing alpha-synuclein called Lewy bodies. Viral vector-induced overexpression of alpha-synuclein in dopaminergic neurons represents a model of PD which recapitulates disease progression better than commonly used neurotoxin models. Previous studies using this model have reported motor and cognitive impairments, whereas depression, mood and anxiety phenotypes are less described. To investigate these psychiatric phenotypes, Sprague-Dawley rats received bilateral injections of a recombinant adeno-associated virus (AAV) vector expressing human alpha-synuclein or GFP into the substantia nigra pars compacta. Behavior was assessed at two timepoints: 3 and 8 weeks post-injection. We report that nigral alpha-synuclein overexpression led to a pronounced nigral dopaminergic cell loss accompanied by a smaller cell loss in the ventral tegmental area, and to a decreased striatal density of dopaminergic fibers. The AAV-alpha-synuclein group exhibited modest, but significant motor impairments 8 weeks after vector administration. The AAV-alpha-synuclein group displayed depressive-like behavior in the forced swim test after 3 weeks, and reduced sucrose preference at week 8. At both timepoints, overexpression of alpha synuclein was linked to a hyperactive hypothalamic-pituitary-adrenal (HPA) axis regulation of corticosterone. The depressive-like phenotype was also correlated with decreased nigral brain-derived neurotrophic factor and spinophilin levels, and with decreased striatal levels of the activity-regulated cytoskeleton associated protein. This study demonstrates that AAV-mediated alpha-synuclein overexpression in dopamine neurons is not only useful to model motor impairments of PD, but also depression. This study also provides evidence that depression in experimental Parkinsonism is correlated to dysregulation of the HPA axis and to alterations in proteins involved in synaptic plasticity. PMID- 26363496 TI - (R1441C) LRRK2 induces the degeneration of SN dopaminergic neurons and alters the expression of genes regulating neuronal survival in a transgenic mouse model. AB - Mutation of leucine-rich repeat kinase 2 (LRRK2) is the most common genetic cause of both familial and sporadic Parkinson's disease (PD) cases. Several mutations in LRRK2 gene were reported in PD patients. R1441 is the second most frequent site of LRRK2 mutation. We generated (R1441C) LRRK2 transgenic mice that displayed motor deficits at the age of 16 months. Compared with wild-type mice, 16-month-old (R1441C) LRRK2 mice exhibited a significant reduction in the number of substantia nigra (SN) dopaminergic neurons. To elucidate molecular pathogenic pathways involved in (R1441C) LRRK2-induced death of SN dopaminergic neurons, we performed microarray analysis to visualize altered mRNA expressions in the SN of (R1441C) LRRK2 mouse. In the SN of (R1441C) LRRK2 transgenic mouse, the mRNA expression of three genes that promote cell death was upregulated, while the mRNA expression of seven genes that contribute to neurogenesis/neuroprotection was significantly downregulated. Our results suggest that altered expression of these genes involved in regulating neuronal survival may contribute to the pathogenesis of (R1441C) LRRK2-induced PD. PMID- 26363497 TI - Update on the efficacy of extracorporeal shockwave treatment for myofascial pain syndrome and fibromyalgia. AB - Chronic muscle pain syndrome is one of the main causes of musculoskeletal pathologies requiring treatment. Many terms have been used in the past to describe painful muscular syndromes in the absence of evident local nociception such as myogelosis, muscle hardening, myalgia, muscular rheumatism, fibrositis or myofascial trigger point with or without referred pain. If it persists over six months or more, it often becomes therapy resistant and frequently results in chronic generalized pain, characterized by a high degree of subjective suffering. Myofascial pain syndrome (MPS) is defined as a series of sensory, motor, and autonomic symptoms caused by a stiffness of the muscle, caused by hyperirritable nodules in musculoskeletal fibers, known as myofascial trigger points (MTP), and fascial constrictions. Fibromyalgia (FM) is a chronic condition that involves both central and peripheral sensitization and for which no curative treatment is available at the present time. Fibromyalgia shares some of the features of MPS, such as hyperirritability. Many treatments options have been described for muscle pain syndrome, with differing evidence of efficacy. Extracorporeal Shockwave Treatment (ESWT) offers a new and promising treatment for muscular disorders. We will review the existing bibliography on the evidence of the efficacy of ESWT for MPS, paying particular attention to MTP (Myofascial Trigger Point) and Fibromyalgia (FM). PMID- 26363498 TI - A new step aeration approach towards the improvement of nitrogen removal in a full scale Carrousel oxidation ditch. AB - Two aeration modes, step aeration and point aeration, were used in a full-scale Carrousel oxidation ditch with microporous aeration. The nitrogen removal performance and mechanism were analyzed. With the same total aeration input, both aeration modes demonstrated good nitrification outcomes with the average efficiency in removing NH4(+)-N of more than 98%. However, the average removal efficiencies for total nitrogen were 89.3% and 77.6% under step aeration and point aeration, respectively. The results indicated that an extended aerobic zone followed the aeration zones could affect the proportion of anoxic and oxic zones. The step aeration with larger anoxic zones indicated better TN removal efficiency. More importantly, step aeration provided the suitable environment for both nitrifiers and denitrifiers. The diversity and relative abundance of denitrifying bacteria under the step aeration (1.55%) was higher than that under the point aeration (1.12%), which resulted in an overall higher TN removal efficiency. PMID- 26363499 TI - High production of erythritol from Candida sorbosivorans SSE-24 and its inhibitory effect on biofilm formation of Streptococcus mutans. AB - Amongst different isolates screened for erythritol production, isolate no. SSE-24 was found to be the best erythritol producer and identified as Candida sorbosivorans SSE-24. Statistical optimization was used to determine the optimum level of the significant variables for maximum erythritol production. The interactive effects of glucose, inoculum level and yeast extract were determined to be significant. The optimum medium composition for erythritol production was 160 g/L glucose, 12 g/L yeast extract, 10% inoculum level and 0.35 g/L FeSO4?7H2O. The production of erythritol was successfully scaled up to a 30 L level, where 60.20 g/L of erythritol was produced, with a yield of 0.38 g/g. The fermentation broth was purified by activated charcoal followed by vacuum concentration, ion exchange chromatography and crystallization. Purity of erythritol was further determined by NMR. Significant inhibitory effect of erythritol on growth (>78%) and biofilm formation (40.2%) of Streptococcus mutans enhances the importance of this study. PMID- 26363500 TI - Simultaneous saccharification and co-fermentation of dry diluted acid pretreated corn stover at high dry matter loading: Overcoming the inhibitors by non-tolerant yeast. AB - Dry dilute acid pretreatment (DDAP) is a promising method for lignocellulose bioconversion, although inhibitors generated during the pretreatment impede the fermentation severely. We developed the simultaneous saccharification and co fermentation (SScF) of DDAP pretreated biomass at high solid loading using xylose fermenting Saccharomyces cerevisiae, SyBE005. Effect of temperature on SScF showed that ethanol yield at 34 degrees C was 10.2% higher than that at 38 degrees C. Ethanol concentration reached 29.5 g/L at 15% (w/w) dry matter loading, while SScF almost ceased at the beginning at 25% (w/w) dry matter loading of DDAP pretreated corn stover. According to the effect of the diluted hydrolysate on the fermentation of strain SyBE005, a fed-batch mode was developed for the SScF of DDAP pretreated corn stover with 25% dry matter loading without detoxification, and 40.0 g/L ethanol was achieved. In addition, high yeast inoculation improved xylose utilization and the final ethanol concentration reached 47.2 g/L. PMID- 26363502 TI - Impurities contained in antifungal drug ketoconazole are potent activators of human aryl hydrocarbon receptor. AB - Antifungal drug ketoconazole is a mixture of (+)/(-) cis-enantiomers, which also contains several impurities. Ketoconazole was identified as an activator of aryl hydrocarbon receptor AhR by three independent research teams. In the current paper we demonstrate that impurities contained in ketoconazole preparations are strong activators of human AhR and inducers of CYP1A1. Impurity IMP-C had similar potency (EC50), but 10-15 times higher efficacy (magnitude of induction) towards AhR, comparing to (+)-ketoconazole, as revealed by gene reporter assay in AZ-AHR stably transfected cells. Impurities IMP-B and IMP-C, and in lesser extent IMP-E, induced a formation of AhR-DNA complex, as demonstrated by electromobility shift assay EMSA. Impurities IMP-C and IMP-E dose-dependently induced CYP1A1 mRNA after 24 h, and their effects were comparable to those by (+)-ketoconazole. The level of CYP1A1 protein in HepG2 cells was strongly increased by IMP-C after 48h. In conclusion, our data further elucidated molecular effects of ketoconazole towards AhR signaling pathway, with possible implications in ketoconazole role in skin chemoprevention and/or damage, involving AhR. PMID- 26363501 TI - Valorisation of mixed bakery waste in non-sterilized fermentation for L-lactic acid production by an evolved Thermoanaerobacterium sp. strain. AB - In this study, an advanced biorefinery technology that uses mixed bakery waste has been developed to produce l-lactic acid using an adaptively evolved Thermoanaerobacterium aotearoense LA1002-G40 in a non-sterilized system. Under these conditions, mixed bakery waste was directly hydrolysed by Aspergillus awamori and Aspergillus oryzae, resulting in a nutrient-rich hydrolysate containing 83.6g/L glucose, 9.5 g/L fructose and 612 mg/L free amino nitrogen. T. aotearoense LA1002-G40 was evaluated and then adaptively evolved to grow in this nutrient-rich hydrolysate. Using a 5-L fermenter, the overall lactic acid production from mixed bakery waste was 0.18 g/g with a titer, productivity and yield of 78.5 g/L, 1.63 g/L/h and 0.85 g/g, respectively. This is an innovative procedure involving a complete bioconversion process for l-lactic acid produced from mixed bakery waste under non-sterilized conditions. The proposed process could be potentially applied to turn food waste into l-lactic acid in an economically feasible way. PMID- 26363503 TI - Effect of PCB 126 on aryl hydrocarbon receptor 1 (AHR1) and AHR1 nuclear translocator 1 (ARNT1) mRNA expression and CYP1 monooxygenase activity in chicken (Gallus domesticus) ovarian follicles. AB - The aim of the experiment was to study the in vitro effect of 3,3',4,4',5 pentachlorobiphenyl (PCB 126; a coplanar PCB congener) on aryl hydrocarbon receptor (AHR1) and AHR1 nuclear translocator (ARNT1) mRNA expression and the activity of CYP1 family monooxygenases in chicken ovarian follicles. White (1-4 mm) and yellowish (4-8 mm) prehierarchical follicles as well as fragments of the theca and granulosa layers of the 3 largest preovulatory follicles (F3-F1) were incubated in a medium supplemented with 0 (control group), 1, 10 or 100 nM PCB 126. The incubation was carried out for 6 h or 24 h for determination of mRNA expression of AHR1 and ARNT1 genes (real-time qPCR) and CYP1 monooxygenase activity (EROD and MROD fluorometric assays), respectively. It was found that chicken ovarian follicles express mRNA of AHR1 and ARNT1 genes. A modulatory effect of PCB 126 on AHR1 and ARNT1 expression depended not only on the biphenyl concentration but also on the follicular layer and the maturational state of the follicle. EROD and MROD activities appeared predominantly in the granulosa layer of the yellow preovulatory follicles. PCB 126 induced these activities in a dose dependent manner in all ovarian follicles. The obtained results suggest that ovarian follicles, especially the granulosa layer, are involved in the detoxification process of PCBs in the laying hen. Taking this finding into consideration it can be suggested that the granulosa layer of the yellow hierarchical follicles plays a key role in the protective mechanism which reduces the amount of transferred dioxin-like compounds into the yolk of the oocyte. PMID- 26363504 TI - On resonance phase alternated CWFP sequences for rapid and simultaneous measurement of relaxation times. AB - T1 and T2 relaxation times have been frequently used as probes for physical chemical properties in several time-domain NMR applications (TD-NMR) such as food, polymers and petroleum industries. T2 measurements are usually achieved using the traditional Carr-Purcell-Meiboom-Gill (CPMG) pulse sequence because it is a fast and robust method. On the other hand, the traditional methods for determining T1, i.e., inversion and saturation recovery, are time-consuming, driving several authors to develop rapid 1D and 2D methods to obtain T1 and T2 or T1/T2 ratio. However, these methods usually require sophisticated processing and/or high signal to noise ratio (SNR). This led us to develop simple methods for rapid and simultaneous determination of T1 and T2 using Continuous Wave Free Precession (CWFP) and Carr-Purcell Continuous Wave Free Precession (CP-CWFP) pulse sequences. Nevertheless, a drawback of these sequences is that they require specific adjustment of the frequency offset or the time interval between pulses (Tp). In this paper we present an alternative form of these sequences, named CWFPx-x, CP-CWFPx-x, where a train of pi/2 pulses with phases alternated by pi enable performing the experiments on-resonance and independently of Tp, when Tp 100 fL). Cognition was assessed by delayed word recall test (DWRT), digit symbol substitution test (DSST), word fluency test (WFT), and global Z-score at Visit 2 (1990-1992) and Visit 4 (1996-1998). Adjusted linear regression models and splines were used. RESULTS: Cross-sectionally, anemia overall was associated with lower cognitive test scores on DSST and global Z-score among men and women (all p < .05), but not on DWRT or WFT. Anemia subtypes were associated similarly with cognition, with strongest associations for the DSST and global Z-score. Additionally, elevated hemoglobin level was associated with nonsignificantly worse cognition in cross-sectional analyses, suggesting a nonlinear association of hemoglobin with cognition. In contrast, anemia overall and anemia subtypes were not associated with cognition in prospective analyses (all p > .05). CONCLUSIONS: There was a cross-sectional, but not prospective, nonlinear association between hemoglobin concentrations and cognitive function, although only associations of low levels of hemoglobin (anemia) were statistically significant. Subtypes of anemia had similar magnitudes of associations with cognition. PMID- 26363512 TI - Rey-Lopez et al. respond to "the metabolically healthy obesity phenotype". PMID- 26363513 TI - Is the metabolically healthy obesity phenotype an irrelevant artifact for public health? AB - Some obese persons do not develop (at least in the short term) the metabolic complications of obesity that are thought to be causally linked to cardiovascular events or premature mortality. This phenomenon has been termed "metabolically healthy obesity" (MHO), and it has received much attention recently, to the extent that some authors argue that "new metrics" must be developed to estimate the risk associated with obesity beyond body mass index. In this commentary, we argue that the MHO phenotype is not benign and as such has very limited relevance as a public health target. More efforts must be allocated to reducing the distal and actual causal agents that lead to weight gain, instead of the current disproportionate scientific interest in the biological processes that explain the heterogeneity of obesity. PMID- 26363514 TI - Trajectories of Body Mass Index and Their Associations With Mortality Among Older Japanese: Do They Differ From Those of Western Populations? AB - Few studies have focused on the relationship between the trajectories of long term changes in body mass index (BMI; weight (kg)/height (m)(2)) and all-cause mortality in old age, particularly in non-Western populations. We evaluated this association by applying group-based mixture models to data derived from the National Survey of the Japanese Elderly, which included 4,869 adults aged 60 or more years, with up to 7 repeated observations between 1987 and 2006. Four distinct BMI trajectories were identified: "low-normal weight, decreasing" (baseline BMI = 18.7; 23.8% of sample); "mid-normal weight, decreasing" (baseline BMI = 21.9; 44.6% of sample); "high-normal weight, decreasing" (baseline BMI = 24.8; 26.5% of sample); and "overweight, stable" (baseline BMI = 28.7; 5.2% of sample). Survival analysis with an average follow-up of 13.8 years showed that trajectories of higher BMI were associated with lower mortality. In particular, relative to those with a mid-normal weight, decreasing BMI trajectory, those with an overweight, stable BMI trajectory had the lowest mortality, and those with a low-normal, decreasing BMI trajectory had the highest mortality. In sharp contrast with prior observations from Western populations, BMI changes lie primarily within the normal-weight range, and virtually no older Japanese are obese. The association between BMI trajectories and mortality varies according to the distribution of BMI within the population. PMID- 26363515 TI - Invited commentary: limitations and usefulness of the metabolically healthy obesity phenotype. AB - The fraction of the obese population who appear to be free of the metabolic abnormalities that usually accompany excess adiposity has garnered a great deal of attention recently. The so-called "metabolically healthy obesity" concept is thought to offer a refinement of the traditional obesity definitions that are based solely on anthropometry. The commentary by Rey-Lopez et al. (Am J Epidemiol. 2015;182(9):737-741) in this issue of the Journal highlights several limitations of the "metabolically healthy obesity" concept and calls into question its usefulness as a public health metric. We discuss several of the issues raised by these authors and offer some perspective on why the utility of this concept remains unresolved. PMID- 26363516 TI - Anal Fistula Plug for Perianal Fistulising Crohn's Disease: an Important Trial for Inflammatory Bowel Disease Surgeons. PMID- 26363517 TI - A Case of Cronkhite-Canada Syndrome with a Colitis-mimicking Endoscopic Presentation. PMID- 26363518 TI - Vascular Anomalies and Inflammatory Bowel Disease. PMID- 26363519 TI - From cell to cell: the breakdown of intercellular connectivity after stroke and how to regain contact. PMID- 26363520 TI - Did the adoption of accelerated partial-breast irradiation reduce the noncompliance with adjuvant radiation in lumpectomy patients? AB - BACKGROUND: The underutilization of radiation therapy after breast-conserving surgery in early-stage breast cancer patients has been attributed to the inconvenience and potential side effects of whole-breast radiation treatment regimens. Accelerated partial-breast irradiation (APBI) involves twice-daily treatments more than 4 to 5 days, which could potentially improve convenience and adherence for women undergoing treatment. METHODS: We studied local therapies in about one-third of a million female breast cancer patients who were diagnosed between January 2000 and June 2011. RESULTS: We found that the use of APBI brachytherapy increased rapidly from .2% in 2000 to about 3.1% in 2008 and leveled off after 2009. The increased use of APBI did not reduce the percentage of early-stage breast cancer patients who improperly forego radiation (about 14% over the whole study period). CONCLUSIONS: Noncompliance with adjuvant radiation is still common when shortened radiation therapy becomes increasingly accessible. PMID- 26363521 TI - HLA-DR*0401 expression in the NOD mice prevents the development of autoimmune diabetes by multiple alterations in the T-cell compartment. AB - Several human HLA alleles have been found associated with type 1 diabetes (T1D), but their precise role is not clearly defined. Herein, we report that a human MHC class II (HLA-DR*0401) allele transgene that has been expressed into NOD (H 2(g7)I-E(null)) mice prone to T1D rendered the mice resistant to the disease. T1D resistance occurred in the context of multi-point T-cell alterations such as: (i) skewed CD4/CD8 T-cell ratio, (ii) decreased size of CD4(+)CD44(high) T memory pool, (iii) aberrant TCR Vbeta repertoire, (iv) increased neonatal number of Foxp3(+) and TR-1(+) regulatory cells, and (v) reduced IFN-gamma inflammatory response vs. enhanced IL-10 suppressogenic response of T-cells upon polyclonal and antigen-specific stimulation. The T-cells from NOD/DR4 Tg mice were unable to induce or suppress diabetes in NOD/RAG deficient mice. This study describes a multifaceted regulatory function of the HLA-DR*0401 allele strongly associated with the lack of T1D development in NOD mice. PMID- 26363522 TI - ERK1, 2, and 5 expression and activation in dopaminergic brain regions during postnatal development. AB - Degeneration and dysfunctioning of dopaminergic neurons in the midbrain have been associated with serious neurodegenerative and neuropsychiatric disorders. Elucidating the underlying neurobiology of these neurons during early postnatal development may provide important information regarding the etiology of these disorders. Cellular signaling pathways have been shown to regulate postnatal neuronal development. Among several signaling pathways, extracellular-regulated mitogen kinases (ERK) 1, 2, and 5 have been shown to be crucial for the survival and function of dopaminergic neurons. In this study, the basal expression and activation of ERK1, 2, and 5 were studied during postnatal development in regions rich in DA cells and terminals. In the striatum (STR) and ventral mesencephalon regions of the substantia nigra (SN) and ventral tegmental area (VTA), ERK5 expression and activation were high during early postnatal days and declined with aging. Interestingly, sharp increases in phosphorylated or activated ERK1 and ERK2 were observed at postnatal day (PND) 7 in the SN and VTA. In contrast, in the STR, the levels of phosphorylated ERK1 and 2 were significantly higher at PND0 than at any other PND examined. Overall, the understanding of alterations in ERK signaling in regions rich in DA cells and DA terminals during postnatal neuronal development may provide information about their role in regulation of dopamine neuronal development which may ultimately provide insight into the underlying mechanisms of dopamine neurodegeneration. PMID- 26363523 TI - Age-dependent differential expression profile of a novel intergenic long noncoding RNA in rat brain. AB - Long noncoding RNAs (lncRNAs) are >=200 nt long, abundant class of non-protein coding RNAs that are transcribed in complex, sense- and antisense patterns from the intergenic and intronic regions of mammalian genome. Mammalian central nervous system constitutes the largest repertoire of noncoding transcripts that are known to be expressed in developmentally regulated and cell-type specific manners. Although many lncRNAs, functioning in the brain development and diseases are known, none involved in brain aging has been reported so far. Here, we report involvement of a novel, repeat sequence (simple repeats and SINES)-containing, trans-spliced, long intergenic non-protein coding RNA (lincRNA), named as LINC RBE (rat brain expressed transcript) involved in maturation and aging of mammalian brain. The LINC-RBE is strongly expressed in the rat brain and the upstream/downstream sequences of its DNA in the chromosome 5 contain binding sites for many cell growth, survival and development-specific transcriptional factors. Through RT-PCR and RNA in situ hybridization, LINC-RBE was found to be expressed in an age-dependent manner with significantly higher level of expression in the brain of adult (16 weeks) compared to both immature (4 weeks) and old (70 weeks) rats. Moreover, the expression pattern of the LINC-RBE showed distinct association with the specific neuro-anatomical regions, cell types and sub-cellular compartments of the rat brain in an age-related manner. Thus, its expression increased from immature stage to adulthood and declined further in old age. This is a first-time report of involvement of an intergenic repeat sequence containing lncRNA in different regions of the rat brain in an age-dependent manner. PMID- 26363524 TI - Association between sleep duration and obesity is modified by dietary macronutrients intake in Korean. AB - BACKGROUND: Short sleep duration has been reported to be inversely associated with risk of obesity. METHODS: The effects of sleep duration on obesity-related variables and the interaction of sleep duration and dietary macronutrients consumption on risk of obesity were analysed in 14,111 subjects aged 20-79 from the Korean National Health and Nutrition Examination Survey. RESULTS: Sleep restriction to less than 7h per day resulted in higher body mass index, plasma triglyceride level, and obesity prevalence for women, but not for men. Protein intake was significantly lower in subjects with lower sleep duration for both men and women. The subjects with short sleep duration were significantly higher fat consumption for men, whereas carbohydrate consumption for women. Among subjects whose carbohydrate consumption was above the median, subjects with sleep duration of less than 7h per day increased their odds of being obese (OR=1.255, 95% CI: 1.073-1.476, P<0.001) compared to subjects with sleep duration more than 7h per day for women. CONCLUSIONS: Our results showed that sleep duration positively correlated with protein consumption, but negatively correlated with carbohydrate consumption, which might lead to high risk of obesity for women. Also, our findings support a significant association between sleep duration and obesity related variables and this association has been potentially modified by dietary macronutrients consumption in women subjects. PMID- 26363525 TI - Indolent T-lymphoblastic proliferation: a name with specific meaning. PMID- 26363526 TI - GRIM-19 expression is a potent prognostic marker in colorectal cancer. AB - Retinoid-interferon-induced mortality-19 (GRIM-19), a recently discovered cell death regulatory gene, may function as a tumor suppressor in many human malignancies. However, the expression of GRIM-19 in and its prognostic value for patients with colorectal cancer (CRC) have not been well investigated to date. Here, GRIM-19 expression was measured immunohistochemically in 94 colon samples and by quantitative real-time reverse transcriptase polymerase chain reaction in 15 paired CRC tissues and adjacent normal tissues. The prognostic significance was assessed using Kaplan-Meier survival estimates and log-rank tests. Our results showed that GRIM-19 mRNA and protein levels in adenoma tissues were similar to those in adjacent normal tissues. However, GRIM-19 expression was severely depressed in carcinomas compared to matched normal tissues (P = .000). Additionally, we found GRIM-19 to be located in both the cytoplasm and nucleus in normal tissues but only in the cytoplasm in CRC tissues. Alteration in GRIM-19 expression occurs early in the pathogenesis of CRC; moreover, low GRIM-19 expression was associated with poor tumor differentiation (P = .013), the presence of lymph nodes (P = .000), metastasis to other organs (P = .045) and vascular invasion (P = .010). During a mean period of 40 months follow-up, patients without GRIM-19 had a statistically significantly lower rate of recurrence/metastasis (P < .05) and a shorter overall survival time (P < .01) than the patients with GRIM-19 expression. Taken together, GRIM-19 expression is closely associated with CRC progression and might be a very promising prognostic biomarker for CRC patients. PMID- 26363527 TI - Autophagy-related genes Raptor, Rictor, and Beclin1 expression and relationship with multidrug resistance in colorectal carcinoma. AB - This study aims to evaluate the relationship between the expressions of autophagy related genes Raptor, Rictor, and Beclin1 and the expression of multidrug resistance (MDR) gene in colorectal cancer (CRC) patients. Immunohistochemistry and real-time polymerase chain reaction were used to detect the protein and messenger RNA expressions of mammalian target of rapamycin (mTOR), Raptor, Rictor, Beclin1, light chain 3 (LC3), and MDR-1 in 279 CRC specimens. Patients were followed up annually by telephone or at an outpatient clinic. Results revealed that the protein and messenger RNA expressions of Beclin1, LC3, mTOR, Raptor, Rictor, and MDR-1 in CRC are significantly higher than in adjacent tissues. LC3 expression in poorly differentiated CRC is higher than that in well differentiated CRC, and the expression of mTOR, Raptor, Rictor, and LC3 in lymph node metastasis is higher than that obtained in the absence of lymph node metastasis. The expression of LC3 is positively correlated with those of Beclin1 and Rictor and negatively correlated with Raptor and mTOR in CRC. The expression of Raptor is negatively correlated with Rictor. The expression of MDR-1 is positively correlated with those of Beclin1, LC3, and Rictor and negatively correlated with Raptor and mTOR. Kaplan-Meier analysis revealed that the 5-year survival rate of patients without lymph node metastasis; positive expression of Rictor, Beclin1, and LC3; and negative expression of Raptor and mTOR were higher than those with these characteristics. To conclude, the expressions of Beclin1, Raptor, and Rictor are related to the development and progression of colorectal carcinoma and MDR. ( CLINICAL TRIAL REGISTRATION NUMBER: 2014-009-01.). PMID- 26363528 TI - Characterization of estrogen receptor-negative/progesterone receptor-positive breast cancer. AB - Despite the controversies, estrogen receptor-negative/progesterone receptor positive (ER-/PR+) breast cancers have a reported incidence of 1% to 4%. These tumors are less well defined, and it is unclear whether ER-/PR+ represents a distinct subtype. Thus, we analyzed 5374 consecutive breast cancers to characterize the clinicopathological features of this underrecognized subset of tumors. The ER-/PR+ tumors, constituting 2.3% of the total, were mostly high grade and significantly seen in younger patients and African American women when compared with the ER+/PR+ and ER+/PR- groups, but similar to that of ER-/PR- phenotype (P < .0001). A significantly prolonged relapse-free survival (RFS) was associated with the ER+/PR+ subtype when compared with the ER+/PR- (P = .0002) or ER-/PR+ (P = .0004) tumors, whereas all 3 groups showed a superior outcome to that of the ER-/PR- phenotype. In the subset of patients receiving endocrine therapy, those with ER+/PR+ tumors had a significantly prolonged RFS (P = .001) and disease-specific survival (P = .005) when compared with the group with an ER+/PR- phenotype, but did not significantly differ from those with ER-/PR+ tumors. No significant survival advantage was found between the ER+/PR- and ER /PR+ tumors in any group of patients analyzed. Furthermore, a higher PR expression was associated with a favorable RFS and disease-specific survival in the patients with ER-/PR+ tumors. Therefore, the ER-/PR+ tumors demonstrate a similar, if not higher than, response rate to endocrine therapy when compared with the ER+/PR- tumors and thus are important to identify. Routine PR testing remains necessary in assisting clinical decision making in the pursuit of precision medicine. PMID- 26363529 TI - Smoking is associated with increased resting energy expenditure in the general population: The NEO study. AB - OBJECTIVE: Animal studies and human studies in small selected populations have shown a positive association between nicotine smoking and resting energy expenditure (REE), but data in large cohorts are lacking. We aimed to investigate the association between smoking behavior and REE in a large, population-based study. DESIGN: Population-based cross-sectional study. METHODS: In this cross sectional analysis of baseline measurements from the Netherlands Epidemiology of Obesity (NEO) study (n=6673), we included participants with REE measurement by indirect calorimetry who were not using lipid or glucose lowering drugs (n=1189). We used linear regression analysis to examine the association of smoking status (never, former, occasional, current smoker) and smoking quantity (pack years) with REE per kilogram (kg) fat free mass (FFM) and with REE adjusted for FFM. Models were adjusted for age, sex, ethnicity, educational level, physical activity, energy intake and body mass index (BMI). RESULTS: Mean (standard deviation, SD) age was 55.2 (5.9) years and BMI was 26.3 (4.4) kg/m(2). 60% of the participants were women. Mean (SD) REE/FFM (kcal/day/kg FFM) was for male never smokers 25.1 (2.0), male current smokers 26.4 (2.8), female never smokers 28.9 (2.5) and female current smokers 30.1 (3.7). After adjustment, only current smokers had a higher REE/FFM (mean difference 1.28, 95% CI 0.64, 1.92), and a higher REE adjusted for FFM (mean difference 60.3 kcal/day, 95% CI 29.1, 91.5), compared with never smokers. There was no association between pack years and REE/FFM (mean difference -0.01, 95% CI -0.06, 0.04) or REE adjusted for FFM (mean difference 0.2, 95% CI -2.4, 2.8) in current smokers. CONCLUSION: Current smoking is associated with a higher resting energy expenditure compared with never smoking in a large population-based cohort. PMID- 26363531 TI - Vale Professor Patrick Wall. AB - Professor Patrick Wall changed the way we think about pain. Until the middle of the 20th Century, pain was considered primarily to be a symptom of disease or injury. Pain was classically viewed in terms of a single mechanism consisting of a modality-specific, hard-wired system of nerve fibres running between the periphery and a specific pain centre in the brain. The implication of this view was that pain could only result from clear tissue pathology, with the result that physiotherapy treatment was often directed at the peripheral source of the pain. However, this does not fit with clinical observation, in that there is little correlation between the amount of tissue damage suffered by patients and the degree of pain that they feel. PMID- 26363530 TI - [Pneumococcal infections: Appraisal and perspectives in terms of adult vaccination]. AB - Pneumococcal diseases are the first cause of bacterial infections in adult and in the aged adult. While its considerable morbi-mortality is potentially preventable through vaccination, the interest of anti-pneumococcal vaccination in these populations is still debated. Effectiveness appraisal of current anti pneumococcal vaccines and the perspectives in terms of preventive strategies against Streptococcus pneumoniae infections in the adult population are presented. PMID- 26363532 TI - Exploring inter-subject anatomic variability using a population of patient specific femurs and a statistical shape and intensity model. AB - This paper is motivated by the need to accurately and efficiently measure key periosteal and endosteal parameters of the femur, known to critically influence hip biomechanics following arthroplasty. The proposed approach uses statistical shape and intensity models (SSIMs) to represent the variability across a wide range of patients, in terms of femoral shape and bone density. The approach feasibility is demonstrated by using a training dataset of computer tomography scans from British subjects aged 25-106 years (75 male and 34 female). For each gender, a thousand new virtual femur geometries were generated using a subset of principal components required to capture 95% of the variance in both female and male training datasets. Significant differences were found in basic anatomic parameters between females and males: anteversion, CCD angle, femur and neck lengths, head offsets and radius, cortical thickness, densities in both Gruen and neck zones. The measured anteversion for female subjects was found to be twice as high as that for male subjects: 13 +/- 6.4 degrees vs. 6.3 +/- 7.8 degrees using the training datasets compared to 12.96 +/- 6.68 vs. 5.83 +/- 9.2 using the thousand virtual femurs. No significant differences were found in canal flare indexes. The proposed methodology is a valuable tool for automatically generating a large specific population of femurs, targeting specific patients, supporting implant design and femoral reconstructive surgery. PMID- 26363533 TI - Alison's Story--A Cautionary Tale in the Age of Genomic Medicine. AB - Alison's story illustrates the disastrous consequences of not securing an accurate family history when evaluating a patient for solid tumor malignancy; this is even more acute when the patient is diagnosed at a young age or has other close relatives affected by the disease. Rapidly advancing genomic technologies directly challenge traditional management practices of referring all patients who may require genetic testing to a genetic counselor or clinical genetics service because next-generation targeted molecular therapies may be indicated based on genomic DNA analysis and may be required urgently to treat life-threatening advanced disease, at times, before genetic counseling. PMID- 26363534 TI - Securing and Documenting Cancer Family History in the Age of the Electronic Medical Record. AB - Family health history is one of the least expensive, most useful, and most underused methods available to conduct assessments of the genetic aspect of a condition or to target the need for a genetic evaluation. This article introduces to the surgical oncologist the reason and process of collecting family history information. As medical records shift from paper to electronic formats, pedigree drawings are not readily available within the electronic health records. International efforts are underway to develop searchable, updatable, and interoperable formats that can collect family history information to inform clinical decision support for genetic risk assessment. PMID- 26363535 TI - Certified Genetic Counselors: A Crucial Clinical Resource in the Management of Patients with Suspected Hereditary Cancer Syndromes. AB - The role of the cancer genetic counselor in the management of patients with cancer is discussed in this article. This includes explaining what a genetic counselor is trained to do and how they are credentialed and licensed. In addition, the article explains who to refer for cancer genetic counseling. Once referred, the article describes what actually happens in a pretest and posttest cancer genetic counseling session. Use of a cancer genetic registry and how it can help in practice is discussed. Finally, several mechanisms for identifying a cancer genetic counselor at one's institution or nearby are outlined. PMID- 26363536 TI - Confidentiality & the Risk of Genetic Discrimination: What Surgeons Need to Know. AB - In the past decade, laws have been passed to provide legal protections against genetic discrimination. Many members of the public and medical providers are unaware of the legislation, and concerns about genetic privacy can prevent delivery of optimal medical care. Patient health information, including genetic testing and family history, is protected under the Health Insurance Portability and Accountability Act and the Genetic Information Nondiscrimination Act. Additional protections are granted through the Americans with Disabilities Act, state laws, and the Affordable Care Act. Communicating a genetic test result back to a patient is important for medical management decisions and family members. PMID- 26363537 TI - The Genetics of Colorectal Cancer. AB - The hereditary colorectal cancer syndromes comprise a heterogeneous group of conditions with varying cancer risks, gastrointestinal polyp types, nonmalignant findings, and inheritance patterns. Although each one is unique in its own right, these syndromes often have overlapping features, making diagnoses difficult in select cases. Obtaining accurate polyp history (histologic type, number, location, and age of onset), cancer history (location, type, and age of onset), and other nonmalignant features is imperative in determining the likely disease diagnosis and thereby the appropriate genetic tests for precise diagnosis in a timely fashion. This process often necessitates collaboration among surgical oncology team members and genetic counselors. PMID- 26363538 TI - The Genetics of Breast Cancer: What the Surgical Oncologist Needs to Know. AB - This article summarizes the impact of germline predisposition to breast cancer on the surgical management of breast cancer and breast cancer risk. Surgical implications of germline predisposition to breast cancer are now more nuanced due to the application of increasingly more complicated next-generation sequencing based tests. The rapid pace of change will continue to challenge paradigms for genetic cancer risk assessment, which can influence the medical and surgical management of breast cancer risk as well as strategies for screening and for risk reduction. PMID- 26363539 TI - Hereditary Pancreatic Cancer Syndromes. AB - Despite decades of scientific and clinical research, pancreatic ductal adenocarcinoma (PDAC) remains a lethal malignancy. The clinical and pathologic features of PDAC, specifically the known environmental and genetic risk factors, are reviewed here with special emphasis on the hereditary pancreatic cancer (HPC) syndromes. For these latter conditions, strategies are described for their identification, for primary and secondary prevention in unaffected carriers, and for disease management in affected carriers. Nascent steps have been made toward personalized medicine based on the rational use of screening, tumor subtyping, and targeted therapies; these have been guided by growing knowledge of HPC syndromes in PDAC. PMID- 26363540 TI - Hereditary Gastric Cancer Syndromes. AB - Hereditary gastric cancer syndromes are a rare but distinct cause of gastric cancers. The genetic mutations underlying most affected families are unknown. Mutations of CDH1 occur in some patients affected by hereditary diffuse gastric cancer, and is the only practical marker for guiding management. Carriers of CDH1 mutations are at risk for a highly penetrant, aggressive and early-onset diffuse type gastric cancer, and these individuals are usually offered prophylactic total gastrectomy. Further research is required to identify other genetic mutations responsible for these syndromes to improve our understanding of the underlying disease mechanisms and optimize the clinical management of affected individuals. PMID- 26363541 TI - Genetic Testing in the Multidisciplinary Management of Melanoma. AB - Melanoma is increasing in incidence and represents an aggressive type of cancer. Efforts have focused on identifying genetic factors in melanoma carcinogenesis to guide prevention, screening, early detection, and targeted therapy. This article reviews the hereditary risk factors associated with melanoma and the known molecular pathways and genetic mutations associated with this disease. This article also explores the controversies associated with genetic testing and the latest advances in identifying genetic targets in melanoma, which offer promise for future application in the multidisciplinary management of melanoma. PMID- 26363543 TI - Sequence Variants of Uncertain Significance: What to Do When Genetic Test Results Are Not Definitive. AB - Clinical genetic testing for cancer predisposition syndromes often identifies DNA changes whose effects cannot be interpreted easily. These changes, often referred to as variants of uncertain significance (VUS), are not useful for clinical management. In contrast with clearly pathogenic mutations, VUS do not firmly diagnose a specific syndrome at the molecular level and cannot be used to identify with certainty which relatives are mutation carriers and which relatives are free of the syndrome. This article discusses the approach to evaluating VUS and how clinicians can play a key role in advancing the field to benefit all patients. PMID- 26363544 TI - Surgical Oncology Clinics of North America. The Role of Genetic Testing in Surgical Oncology. Foreword. PMID- 26363545 TI - Surgical Oncology in the Age of Genomic Medicine. PMID- 26363546 TI - Effect of home reliner on occlusal relationships and oral mucosa: viscoelastic analyses by smoothed particle hydrodynamics simulation. AB - BACKGROUND: For decades, many reports have expressed negative opinions about home reliner (HR), because it may result in residual ridge resorption. Recently, some clinical studies evaluated HR. However, the effect of HR on occlusal relationships and the oral mucosa remains unclear. Here, we dynamically analyzed the situation in which a patient applies HR to an upper complete denture. METHODS: We numerically simulated the effect of HR on occlusal relationships and the oral mucosa. In the simulation, the thickness of HR was set to 2mm as a proper amount and 4mm as an excessive amount. The loading points were set at the center of the right and left occlusal surfaces of the denture. RESULTS: Compared with the case without using HR, at proper amounts (2mm on the right and left sides), HR suppressed the depression of the ill-fitting denture, and stress on the oral mucosa was decreased. In the excessive HR model (4mm on the right and left sides), the vertical occlusal dimension was increased, and stress on the oral mucosa originally fitted with the denture base was increased. When the denture was modeled in an inclined position (2mm on the left side and 4mm on the right side), stress on the oral mucosa on the left buccal side was markedly increased. CONCLUSION: It was found that when an improper amount of HR was applied, the occlusal vertical dimension increased and the oral mucosa was pressured more than that under non-HR conditions. PMID- 26363542 TI - Multiple Endocrine Neoplasia: Genetics and Clinical Management. AB - Early diagnosis of multiple endocrine neoplasia (MEN) syndromes is critical for optimal clinical outcomes; before the MEN syndromes can be diagnosed, they must be suspected. Genetic testing for germline alterations in both the MEN type 1 (MEN1) gene and RET proto-oncogene is crucial to identifying those at risk in affected kindreds and directing timely surveillance and surgical therapy to those at greatest risk of potentially life-threatening neoplasia. Pancreatic, thymic, and bronchial neuroendocrine tumors are the leading cause of death in patients with MEN1 and should be aggressively considered by at least biannual computed tomography imaging. PMID- 26363547 TI - Autologous Infant and Allogeneic Adult Red Cells Demonstrate Similar Concurrent Post-Transfusion Survival in Very Low Birth Weight Neonates. AB - OBJECTIVE: Based on the hypothesis that neonatal autologous red blood cell (RBC) survival (RCS) is substantially shorter than adult RBC, we concurrently tracked the survival of transfused biotin-labeled autologous neonatal and allogeneic adult RBC into ventilated, very low birth weight infants. STUDY DESIGN: RBC aliquots from the first clinically ordered, allogeneic adult RBC transfusion and from autologous infant blood were labeled at separate biotin densities (biotin labeled RBC [BioRBC]) and transfused. Survival of these BioRBCs populations were concurrently followed over weeks by flow cytometric enumeration using leftover blood. Relative tracking of infant autologous and adult allogeneic BioRBC was analyzed by linear mixed modeling of batched weekly data. When possible, Kidd antigen (Jka and Jkb) mismatches between infant and donor RBCs were also used to track these 2 populations. RESULTS: Contrary to our hypothesis, concurrent tracking curves of RCS of neonatal and adult BioRBC in 15 study infants did not differ until week 7, after which neonatal RCS became shortened to 59%-79% of adult enumeration values for uncertain reasons. Analysis of mismatched Kidd antigen RBC showed similar results, thus, confirming that BioRBC tracking is not perturbed by biotin RBC labeling. CONCLUSIONS: This study illustrates the utility of multidensity BioRBC labeling for concurrent measurement of RCS of multiple RBC populations in vivo. The similar RCS results observed for neonatal and adult BioRBCs transfused into very low birth weight infants provides strong evidence that the circulatory environment of the newborn infant, not intrinsic infant adult RBC differences, is the primary determinant of erythrocyte survival. TRIAL REGISTRATION: Clinicaltrials.gov: NCT00731588. PMID- 26363549 TI - Perspective health promotion policy planning to adapt to climate change. PMID- 26363548 TI - Insulin Sensitivity and beta-Cell Function Improve after Gastric Bypass in Severely Obese Adolescents. AB - OBJECTIVE: To test the hypothesis that insulin secretion and insulin sensitivity would be improved in adolescents after Roux-en-Y gastric bypass (RYGB). STUDY DESIGN: A longitudinal study of 22 adolescents and young adults without diabetes undergoing laparoscopic RYGB (mean age 17.1 +/- 1.42 years; range 14.5-20.1; male/female 8/14; Non-Hispanic White/African American 17/5) was conducted. Intravenous glucose tolerance tests were done to obtain insulin sensitivity (insulin sensitivity index), insulin secretion (acute insulin response to glucose ), and the disposition index as primary outcome variables. These variables were compared over the 1 year of observation using linear mixed modeling. RESULTS: In the 1-year following surgery, body mass index fell by 38% from a mean of 61 +/- 12.3 to 39 +/- 8.0 kg/m(2) (P < .01). Over the year following surgery, fasting glucose and insulin values declined by 54% and 63%, respectively. Insulin sensitivity index increased 300% (P < .01), acute insulin response to glucose decreased 56% (P < .01), leading to a nearly 2-fold increase in the disposition index (P < .01). Consistent with improved beta-cell function, the proinsulin to C peptide ratio decreased by 21% (P < .01). CONCLUSIONS: RYGB reduced body mass index and improved both insulin sensitivity and beta-cell function in severely obese teens and young adults. These findings demonstrate that RYGB is associated with marked metabolic improvements in obese young people even as significant obesity persists. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00360373. PMID- 26363550 TI - Inverse correlation between fibrinogen and bone mineral density in women: Preliminary findings. AB - Hemostatic factors may be involved in bone health. The present preliminary study investigated the association between plasma fibrinogen and bone mineral density (BMD) in perimenopausal women. A significant inverse correlation between fibrinogen and BMD was observed (correlation coefficient = -0.42, p < 0.01). This correlation appeared to be more clearly observed in the subgroup with a high level of high-sensitivity C-reactive protein than in that with a low level of high-sensitivity C-reactive protein, and in the subgroup with a high level of diacron reactive oxygen metabolites (an oxidative stress marker) than in that with a low level of diacron reactive oxygen metabolites. Thus, fibrinogen may be a possible marker of BMD in this population. More studies on the associations among hemostasis, inflammation, oxidative stress, and bone metabolism are warranted in the clinical setting. PMID- 26363551 TI - Patch detachment after mitral valve repair with posterior leaflet augmentation: a case report. AB - Mitral valve (MV) repair is indicated for patients with severe MR. We report a case of acute MR caused by patch detachment after posterior leaflet augmentation in MV repair. A 65-year-old male underwent MV repair with posterior leaflet augmentation and coronary artery bypass graft 1 month prior to this study. An inverted T-shaped incision was made on the posterior mitral leaflet (PML), and a piece of autologous fresh pericardium was sewn in the PML defect. Seven days after hospital discharge, he started feeling chest pain and presented with pulseless electrical activity. Ultrasonic cardiography showed severe mitral regurgitation (MR), which was suggestive of acute MR. We performed emergency reoperation. The edge of the autologous pericardial patch was detached from the anterior papillary muscle, and MV replacement was performed. He was discharged from the hospital 55 days after the reoperation and returned to his normal daily life. We conclude that avoidance of tension focalization during MV repair may be important. PMID- 26363552 TI - The role of CYP2A5 in liver injury and fibrosis: chemical-specific difference. AB - Liver injuries induced by carbon tetrachloride (CCL4) or thioacetamide (TAA) are dependent on cytochrome P450 2E1 (CYP2E1). CYP2A5 can be induced by TAA but not by CCL4. In this study, liver injury including fibrosis induced by CCL4 or TAA were investigated in wild-type (WT) mice and CYP2A5 knockout (cyp2a5 (-/-) ) mice as well as in CYP2E1 knockout (cyp2e1 (-/-) ) mice as a comparison. Acute and subchronic liver injuries including fibrosis were induced by CCL4 and TAA in WT mice but not in cyp2e1 (-/-) mice, confirming the indispensable role of CYP2E1 in CCL4 and TAA hepatotoxicity. WT mice and cyp2a5 (-/-) mice developed comparable acute liver injury induced by a single injection of CCL4 as well as subchronic liver injury including fibrosis induced by 1 month of repeated administration of CCL4, suggesting that CYP2A5 does not affect CCL4-induced liver injury and fibrosis. However, while 200 mg/kg TAA-induced acute liver injury was comparable in WT mice and cyp2a5 (-/-) mice, 75 and 100 mg/kg TAA-induced liver injury were more severe in cyp2a5 (-/-) mice than those found in WT mice. After multiple injections with 200 mg/kg TAA for 1 month, while subchronic liver injury as indicated by serum aminotransferases was comparable in WT mice and cyp2a5 (-/-) mice, liver fibrosis was more severe in cyp2a5 (-/-) mice than that found in WT mice. These results suggest that while both CCL4- and TAA-induced liver injuries and fibrosis are CYP2E1 dependent, under some conditions, CYP2A5 may protect against TAA-induced liver injury and fibrosis, but it does not affect CCL4 hepatotoxicity. PMID- 26363554 TI - TRIM39 negatively regulates the NFkappaB-mediated signaling pathway through stabilization of Cactin. AB - NFkappaB is one of the central regulators of cell survival, immunity, inflammation, carcinogenesis and organogenesis. The activation of NFkappaB is strictly regulated by several posttranslational modifications including phosphorylation, neddylation and ubiquitination. Several types of ubiquitination play important roles in multi-step regulations of the NFkappaB pathway. Some of the tripartite motif-containing (TRIM) proteins functioning as E3 ubiquitin ligases are known to regulate various biological processes such as inflammatory signaling pathways. One of the TRIM family proteins, TRIM39, for which the gene has single nucleotide polymorphisms, has been identified as one of the genetic factors in Behcet's disease. However, the role of TRIM39 in inflammatory signaling had not been fully elucidated. In this study, to elucidate the function of TRIM39 in inflammatory signaling, we performed yeast two-hybrid screening using TRIM39 as a bait and identified Cactin, which has been reported to inhibit NFkappaB- and TLR-mediated transcriptions. We show that TRIM39 stabilizes Cactin protein and that Cactin is upregulated after TNFalpha stimulation. TRIM39 knockdown also causes activation of the NFkappaB signal. These findings suggest that TRIM39 negatively regulates the NFkappaB signal in collaboration with Cactin induced by inflammatory stimulants such as TNFalpha. PMID- 26363553 TI - Mitochondrial Lon protease at the crossroads of oxidative stress, ageing and cancer. AB - Lon protease is a nuclear DNA-encoded mitochondrial enzyme highly conserved throughout evolution, involved in the degradation of damaged and oxidized proteins of the mitochondrial matrix, in the correct folding of proteins imported in mitochondria, and in the maintenance of mitochondrial DNA. Lon expression is induced by various stimuli, including hypoxia and reactive oxygen species, and provides protection against cell stress. Lon down-regulation is associated with ageing and with cell senescence, while up-regulation is observed in tumour cells, and is correlated with a more aggressive phenotype of cancer. Lon up-regulation contributes to metabolic reprogramming observed in cancer, favours the switch from a respiratory to a glycolytic metabolism, helping cancer cell survival in the tumour microenvironment, and contributes to epithelial to mesenchymal transition. Silencing of Lon, or pharmacological inhibition of its activity, causes cell death in various cancer cells. Thus, Lon can be included in the growing class of proteins that are not responsible for oncogenic transformation, but that are essential for survival and proliferation of cancer cells, and that can be considered as a new target for development of anticancer drugs. PMID- 26363555 TI - A live attenuated BCG vaccine overexpressing multistage antigens Ag85B and HspX provides superior protection against Mycobacterium tuberculosis infection. AB - Tuberculosis (TB) remains one of the most menacing infectious diseases, although attenuated Mycobacterium bovis Bacillus Calmette-Guerin (BCG) vaccine has been widely used to protect children against primary TB. There are increasing evidences that rapid growing and dormant Mycobacterium tuberculosis (M. tuberculosis) coexist in vivo after infection. However, BCG vaccine only elicits cell-mediated immune responses to secretory antigens expressed by rapid growing pathogen. BCG vaccine is thus unable to thwart the reactivation of latent tuberculosis infection (LTBI), and its protection wanes over age after neonatal immunization. In order to extend its ability for a durable protection, a novel recombinant BCG (rBCG) strain, named rBCG::XB, was constructed by overexpressing immunodominant multistage antigens of Ag85B and HspX, which are expressed by both rapid replicating and dormant M. tuberculosis. Long-term protective effect and immunogenicity of rBCG::XB were compared with the parental BCG in vaccinated C57BL/6 mice. Our results demonstrated that rBCG::XB provided the stronger and long-lasting protection against M. tuberculosis H37Rv intranasal infection than BCG. The rBCG::XB not only elicited the more durable multistage antigen-specific CD4(+)Th1-biased immune responses and specific polyfunctional CD4(+)T cells but also augmented the CD8(+) CTL effects against Ag85B in vivo. In particular, higher levels of CD4(+) TEM and CD8(+) TCM cells, dominated by IL2(+) CD4(+) and CD8(+) TCM cells, were obtained in the spleen of rBCG::XB vaccinated mice. Therefore, our findings indicate that rBCG::XB is a promising candidate to improve the efficacy of BCG. PMID- 26363556 TI - Domain function dissection and catalytic properties of Listeria monocytogenes p60 protein with bacteriolytic activity. AB - The major extracellular protein p60 of Listeria monocytogenes (Lm-p60) is an autolysin that can hydrolyze the peptidoglycan of bacterial cell wall and has been shown to be required for L. monocytogenes virulence. The predicted three dimensional structure of Lm-p60 showed that Lm-p60 could be split into two independent structural domains at the amino acid residue 270. Conserved motif analysis showed that V30, D207, S395, and H444 are the key amino acid residues of the corresponding motifs. However, not only the actual functions of these two domains but also the catalytic properties of Lm-p60 are unclear. We try to express recombinant Lm-p60 and identify the functions of two domains by residue substitution (V30A, D207A, S395A, and H444A) and peptide truncation. The C terminal domain was identified as catalytic element and N-terminal domain as substrate recognition and binding element. Either N-terminal domain truncation or C-terminal domain truncation presents corresponding biological activity. The catalytic activity of Lm-p60 with a malfunctioned substrate-binding domain was decreased, while the substrate binding was not affected by a mulfunctioned catalytic domain. With turbidimetric method, we determined the optimal conditions for the bacteriolytic activity of Lm-p60 against Micrococcus lysodeikficus. The assay for the effect of Lm-p60 on the bacteriolytic activity of lysozyme revealed that the combined use of Lm-p60 protein with lysozyme showed a strong synergistic effect on the bacteriolytic activity. PMID- 26363558 TI - Reliability, validity, and responsiveness of the Japanese version of the Patient Specific Functional Scale in patients with neck pain. AB - PURPOSE: The aims of this study were to translate and culturally adapt the Patient-Specific Functional Scale (PSFS) and validate the Japanese version of the PSFS (PSFS-J) in outpatients with neck pain. METHODS: The PSFS was translated and adapted into Japanese in accordance with the published guidelines. A total of 103 outpatients with neck pain were recruited for this study. Psychometric evaluation included test-retest reliability, convergent validity by comparing the PSFS-J to the Neck Disability Index (NDI), patient's global impression of change (PGIC), and responsiveness (unpaired t test, minimal detectable change). RESULTS: The intraclass correlation coefficient for test-retest reliability was 0.98 (95% confidence interval = 0.95-0.99). The Pearson correlation coefficient with the NDI was -0.35. The Spearman correlation coefficient showed a strong relationship between the change score in the PSFS-J and PGIC (-0.70). The analysis of responsiveness was calculated with the unpaired t test showing a significant difference between the stable and improved patients (P < 0.01). The minimal detectable change was calculated as 0.64. CONCLUSIONS: The Japanese version of the PSFS is a valid, reliable, and responsive instrument to assess Japanese outpatients with neck pain. PMID- 26363557 TI - Efflux systems in bacteria and their metabolic engineering applications. AB - The production of valuable chemicals from metabolically engineered microbes can be limited by excretion from the cell. Efflux is often overlooked as a bottleneck in metabolic pathways, despite its impact on alleviating feedback inhibition and product toxicity. In the past, it has been assumed that endogenous efflux pumps and membrane porins can accommodate product efflux rates; however, there are an increasing number of examples wherein overexpressing efflux systems is required to improve metabolite production. In this review, we highlight specific examples from the literature where metabolite export has been studied to identify unknown transporters, increase tolerance to metabolites, and improve the production capabilities of engineered bacteria. The review focuses on the export of a broad spectrum of valuable chemicals including amino acids, sugars, flavins, biofuels, and solvents. The combined set of examples supports the hypothesis that efflux systems can be identified and engineered to confer export capabilities on industrially relevant microbes. PMID- 26363559 TI - Polyurethane on titanium unconstrained disc arthroplasty versus anterior discectomy and fusion for the treatment of cervical disc disease: a review of level I-II randomized clinical trials including clinical outcomes. AB - PURPOSE: To contrast the clinical and radiologic outcomes and adverse events of anterior cervical discectomy and fusion (ACDF) with a single cervical disc arthroplasty design, the polyurethane on titanium unconstrained cervical disc (PTUCD). METHODS: This is a systematic review of randomized clinical trials (RCT) with evidence level I-II reporting clinical outcomes. After a search on different databases including PubMed, Cochrane Central Register of Controlled Trials, and Ovid MEDLINE, a total of 10 RCTs out of 51 studies found were entered in the study. RTCs were searched from the earliest available records in 2005 to November 2014. RESULTS: Out of a total of 1101 patients, 562 were randomly assigned into the PTUCD arthroplasty group and 539 into the ACDF group. The mean follow-up was 30.9 months. Patients undergoing arthroplasty had lower Neck Disability Index, and better SF-36 Physical component scores than ACDF patients. Patients with PTUCD arthroplasty had also less radiological degenerative changes at the upper adjacent level. Overall adverse events were twice more frequent in patients with ACDF. The rate of revision surgery including both adjacent and index level was slightly higher in patients with ACDF, showing no statistically significant difference. CONCLUSIONS: According to this review, PTUCD arthroplasty showed a global superiority to ACDF in clinical outcomes. The impact of both surgical techniques on the cervical spine (radiological spine deterioration and/or complications) was more severe in patients undergoing ACDF. However, the rate of revision surgeries at any cervical level was equivalent for ACDF and PTUCD arthroplasty. PMID- 26363560 TI - The influence of adjacent level disc disease on discectomy outcomes. AB - PURPOSE: The state of adjacent level discs and its impact on surgical outcomes following single-level lumbar discectomy have not been previously investigated. The purpose of the present study was to determine if a significant relationship exists between the degree of preoperative adjacent level disc degeneration and post-operative clinical outcomes following lumbar discectomy. METHODS: This study retrospectively used preoperative magnetic resonance imaging (MRI) and prospectively collected data from a randomized clinical trial at two tertiary care academic hospitals. Patients who underwent a primary, single-level lumbar discectomy were included. Exclusion criteria included prior lumbar surgery. Outcome measures were the Modified Oswestry Disability Index (ODI) score and Visual Analog Scale (VAS) scores for back and leg pain. These were recorded at baseline and at 3 months, 1, and 2 years postoperatively. An independent reviewer graded adjacent level disc degeneration on all preoperative MRIs using the Pfirrmann grading scale. These data were then analyzed for correlation with each outcome measure. RESULTS: Forty-seven patients were included in the study. No statistically significant correlations were found when comparing preoperative 3 month or 1-year postoperative scores or change from baseline of any outcome measure between Pfirrmann grades. Only about half the patients had 2-year follow up, but at that time point a statistically significant difference in back VAS scores was observed between Pfirrmann groups. No other significant differences were observed at that point. CONCLUSIONS: The degree of preoperative adjacent level degeneration does not significantly affect functional or pain relief outcomes following lumbar discectomy up to 1 year after surgery. PMID- 26363562 TI - [Maxillary advancement osteotomy with sequelae cleft lip and palate: Dilemma between occlusion and aesthetic profile]. AB - INTRODUCTION: Maxillary hypoplasia is a common sequela of cleft lip and palate. Its surgical treatment consists in a maxillary advancement by distraction or by conventional orthognathic surgery but morphological results are unpredictable. Our goal in this study was to see if the esthetical results (on the lip and the nose) of maxillary advancement were correlated to the preservation of lateral incisor space of the cleft side. PATIENTS AND METHOD: This retrospective study included 38 patients operated between 2002 and 2013. Unilateral clefts were studied independently from bilateral clefts. Profile aesthetics was evaluated independently and subjectively by two surgeons and scored on an 8-point scale. The result was classified as "good" if the score was superior or equal to 6. The score was correlated to the following parameters: amount of maxillary advancement, upper incisor axis, preservation of the missing lateral incisor space. RESULTS: In the "good result" group, the space of the lateral incisor was less often preserved. The nasolabial angle was more open and the upper central incisor axis more vertical. These results were more pronounced in bilateral clefts, but also found in unilateral clefts. DISCUSSION: Under reservation of the subjective evaluation and of the small number of patients, it seemed that lateral incisor space closure improved the profile of patients treated by maxillary advancement for cleft lip and palate sequelae. PMID- 26363563 TI - The 1-min sit-to-stand test--A simple functional capacity test in cystic fibrosis? AB - BACKGROUND: We aimed to assess the measurement properties and the minimal important difference (MID) of the 1-min sit-to-stand (STS) test in cystic fibrosis (CF). METHODS: Patients with CF were tested during a pulmonary rehabilitation program. Five STS tests were performed during the program; two tests at the beginning (STS0 and STS1) and three tests at the end (STS2a-2c). Exercise capacity, pulmonary function, and health-related quality of life (HRQoL) and patient-reported health status were measured at the beginning and end of the program. We calculated overall mean, standard deviation, coefficient of variation (CV), and intraclass correlation coefficient (ICC) of the STS test. The MID was calculated using anchor-based and distributional methods. RESULTS: Fourteen participants (8 female, mean age 30.4+/-6.1years) were included. STS test performance increased significantly from STS0 to STS1 indicative of a learning effect. Test-retest reliability for the subsequent STS2a-2c tests was excellent (ICC 0.98, 95% CI 0.96-0.99). The estimated MID for the STS test was 5 repetitions. STS test performance was responsive to change (effect size of 0.97) and correlated with exercise capacity (r=0.63-0.73) and with the physical functioning HRQoL scale (r=0.72). CONCLUSIONS: The 1-min STS test appears to be a reliable, valid, and feasible test to measure functional capacity in patients with CF. PMID- 26363561 TI - Surgery for adult spondylolisthesis: a systematic review of the evidence. AB - Surgery for isthmic and degenerative spondylolisthesis (SL) in adults is carried out very frequently in everyday practice. However, it is still unclear whether the results of surgery are better than those of conservative treatment and whether decompression alone or instrumented fusion with decompression should be recommended. In addition, the role of reduction is unclear. Four clinically relevant key questions were addressed in this study: (1) Is surgery more successful than conservative treatment in relation to pain and function in adult patients with isthmic SL? (2) Is surgery more successful than conservative treatment in relation to pain and function in adult patients with degenerative SL? (3) Is instrumented fusion with decompression more successful in relation to pain and function than decompression alone in adult patients with degenerative SL and spinal canal stenosis? (4) Is instrumented fusion with reduction more successful in relation to pain and function than instrumented fusion without reduction in adult patients with isthmic or degenerative SL? A systematic PubMed search was carried out to identify randomized and nonrandomized controlled trials on these topics. Papers were analyzed systematically in a search for the best evidence. A total of 18 studies was identified and analyzed: two for question 1, eight for question 2, four for question 3, and four for question 4. Surgery appears to be better than conservative treatment in adults with isthmic SL (poor evidence) and also in adults with degenerative SL (good evidence). Instrumented fusion with decompression appears to be more successful than decompression alone in adults with degenerative SL and spinal stenosis (poor evidence). Reduction and instrumented fusion does not appear to be more successful than instrumented fusion without reduction in adults with isthmic or degenerative SL (moderate evidence). PMID- 26363564 TI - Biokinetic analysis of tissue boron (10B) concentrations of glioma patients treated with BNCT in Finland. AB - A total of 98 patients with glioma were treated with BPA-F-mediated boron neutron capture therapy (BNCT) in Finland from 1999 to 2011. Thirty-nine (40%) had undergone surgery for newly diagnosed glioblastoma and 59 (60%) had malignant glioma recurrence after surgery. In this study we applied a closed 3-compartment model based on dynamic (18)F-BPA-PET studies to estimate the BPA-F concentrations in the tumor and the normal brain with time. Altogether 22 patients with recurrent glioma, treated within the context of a clinical trial, were evaluated using their individual measured whole blood (10)B concentrations as an input to the model. The delivered radiation doses to tumor and the normal brain were recalculated based on the modeled (10)B concentrations in the tissues during neutron irradiation. The model predicts from -7% to +29% (average, +11%) change in the average tumor doses as compared with the previously estimated doses, and from 17% to 61% (average, 36%) higher average normal brain doses than previously estimated due to the non-constant tumor-to-blood concentration ratios and considerably higher estimated (10)B concentrations in the brain at the time of neutron irradiation. PMID- 26363565 TI - Mechanical and electromyographic responses during the 3-min all-out test in competitive cyclists. AB - While the 3-min all-out test is an ideal exercise paradigm to study muscle fatigue during dynamic whole-body exercise, so far it has been used mainly to provide insight into the bioenergetic determinants of performance. To shed some light into the development of peripheral muscle fatigue during the 3-min all-out test, we investigated the time course of muscle-fibre conduction velocity (MFCV). Twelve well-trained cyclists (23 +/- 3 yrs) performed an incremental test, a 3 min all-out familiarization trial and a 3-min all-out test. Surface electromyographic signals were detected from the vastus lateralis muscle of the dominant limb. MFCV decreased with power output, though with a somewhat different time course, and the two parameters were strongly correlated (r = 0.87; P < 0.001). A modest decrease in MFCV (17.7 +/- 4.8%), probably due to the endurance characteristics of the subjects, may help explain why a relatively high power output (79 +/- 8% of the peak power output of the incremental test; 60 +/- 14% of the difference between this peak value and the gas exchange threshold) was still maintained at the end of the test. These findings suggest that muscle fatigue substantially affects performance in the 3-min all-out test, expanding on the traditional bioenergetic explanation that performance is limited by rate and capacity of energy supply. PMID- 26363566 TI - [Paediatric prescribing of anti-asthmatics in primary care in Castilla-Leon. Geographical variability]. AB - INTRODUCTION AND OBJECTIVES: Asthma is one of the most prevalent chronic diseases with effective treatment in paediatrics. The aim of this study is to describe the paediatric prescribing of anti-asthmatics in Castilla-Leon, analyzing its geographic variability and temporal evolution. MATERIAL AND METHODS: An analysis was made of prescriptions dispensed in pharmacies of R03 therapeutic subgroup (anti-asthmatic agents), and the active ingredients mepyramine and ketotifen, prescribed in children less than 14 years of age in the Castilla-Leon health service from 2005 to 2010 in Primary Care. Data is presented in prescribed daily doses per thousand inhabitants per day (PDHD) for each active ingredient being calculated raw rates and age-adjusted to the variables health area, type of health zone and year of study. RESULTS: A total of 462,354 prescriptions of anti asthmatic agents were dispensed to a population of 1,580,229 persons/year. There was wide variation between areas in the type and intensity of anti-asthmatic agents used, partly explained by differences in the prevalence of asthma. Montelukast predominated as controller drug in most of them (PDHD 3.1 to 7.7), being similar the consumption intensity in the three types of health zones (PDHD 4.7 to 4.8). The annual variability was low. CONCLUSIONS: The study describes the paediatric prescribing pattern of anti-asthmatic agents in Castilla-Leon between 2005-2010. It shows wide geographical variation, as well as inadequacies regarding current recommendations of asthma treatment. PMID- 26363569 TI - Early Goal-Directed Ventilation: Serving the Greater Good? PMID- 26363568 TI - Marijuana consequences in a motivational context: Goal congruence reduces likelihood of taking steps toward change. AB - This study tested a model of marijuana use, problems, and motivation and barriers to change among a sample of 422 undergraduate students ages 18-25 (M=19.68, SD=1.60) who used marijuana at least once in the past 6 months. We tested a structural equation model (SEM) with use motives (i.e., coping, enhancement, and expansion), perceived use utility, and gender as exogenous variables predicting marijuana use behavior (i.e., use and problems), motivation to change (i.e., problem recognition and perceived costs and benefits of change), and the ultimate outcome, taking steps to reduce marijuana use. Controlling for level of use and problems, expansion motives had a direct effect on increased perceived costs of change and enhancement motives had direct inverse effects on problem recognition and perceived benefits of change. However, the total effect of expansion motives on taking steps was not significant. The perceived role of marijuana in achieving personal strivings (i.e., use utility) was inversely associated with problem recognition, perceived benefits of change, and taking steps toward change. In contrast, coping motives, despite being associated with greater perceived costs of change, were positively associated with taking steps. Problem recognition was positively associated with both increased perceived costs and benefits of reducing marijuana use, reflecting individuals' ambivalence about change. As expected, perceived benefits and costs of reducing use were positively and negatively associated with taking steps toward changing marijuana use, respectively. The results identify individual difference factors that contribute to motivation for change and are consistent with motivational models of change readiness. These results highlight the extent to which integration of marijuana use with personal goal achievement may interfere with taking steps to change use patterns despite associated negative consequences. PMID- 26363567 TI - High seroprevalence of HCV in the Abruzzo Region, Italy: results on a large sample from opt-out pre-surgical screening. AB - PURPOSE: Available estimates of the prevalence of chronic HCV infection in Italy are quite conflicting, varying from 1.5 to 22.5%, with an apparent north to south gradient. As Direct Acting Antivirals are expensive, both National and local governmental Agencies are in urgent need of detailed and reliable estimates of HCV patients to be treated, nationwide and in each district. We investigated the prevalence of anti-HCV antibodies in a large unselected sample of surgical patients providing consent to in-hospital opt-out pre-surgical HCV screening, at two hospitals from the Abruzzo Region, Italy. METHODS: Data were retrieved for 55,533 screened patients (4.1% of the total population in the Abruzzo Region), admitted in the Orthopedic and General Surgery wards of Pescara and Teramo Hospitals from 1999 to 2014. RESULTS: The prevalence of anti-HCV antibodies was 4.4% in the total sample. HCV-positive patients had a mean age of 63.8 +/- 19.9 years; 49.2% were males. From 1999 to 2014, the prevalence of HCV antibodies decreased from 5.4% to 4.1%; at both sites, however, two age-related-peaks were evidenced, the first among patients aged 30-49 years, the second among those older than 70 years. Statistical analyses confirmed a significant trend to decrease over time and a higher prevalence in Pescara and among males (all p < 0.01). CONCLUSIONS: Data retrieved from opt-out pre-surgical screening programs may allow inexpensive and easy-to-perform estimates of HCV seroprevalence from large samples of unselected patients with a well-defined provenience, which may turn useful for future treatment resource allocation. PMID- 26363570 TI - A Clinical Decision Rule to Identify Emergency Department Patients at Low Risk for Acute Coronary Syndrome Who Do Not Need Objective Coronary Artery Disease Testing: The No Objective Testing Rule. AB - STUDY OBJECTIVE: We derive a clinical decision rule for ongoing investigation of patients who present to the emergency department (ED) with chest pain. The rule identifies patients who are at low risk of acute coronary syndrome and could be discharged without further cardiac testing. METHODS: This was a prospective observational study of 2,396 patients who presented to 2 EDs with chest pain suggestive of acute coronary syndrome and had normal troponin and ECG results 2 hours after presentation. Research nurses collected clinical data on presentation, and the primary endpoint was diagnosis of acute coronary syndrome within 30 days of presentation to the ED. Logistic regression analyses were conducted on 50 bootstrapped samples to identify predictors of acute coronary syndrome. A rule was derived and diagnostic accuracy statistics were computed. RESULTS: Acute coronary syndrome was diagnosed in 126 (5.3%) patients. Regression analyses identified the following predictors of acute coronary syndrome: cardiac risk factors, age, sex, previous myocardial infarction, or coronary artery disease and nitrate use. A rule was derived that identified 753 low-risk patients (31.4%), with sensitivity 97.6% (95% confidence interval [CI] 93.2% to 99.5%), negative predictive value 99.6% (95% CI 98.8% to 99.9%), specificity 33.0% (95% CI 31.1% to 35.0%), and positive predictive value 7.5% (95% CI 6.3% to 8.9%) for acute coronary syndrome. This was referred to as the no objective testing rule. CONCLUSION: We have derived a clinical decision rule for chest pain patients with negative early cardiac biomarker and ECG testing results that identifies 31% at low risk and who may not require objective testing for coronary artery disease. A prospective trial is required to confirm these findings. PMID- 26363571 TI - Incidence and Risk Factors for Postcontrast Acute Kidney Injury in Survivors of Sudden Cardiac Arrest. AB - STUDY OBJECTIVE: Survivors of sudden cardiac arrest may be exposed to iodinated contrast from invasive coronary angiography or contrast-enhanced computed tomography, although the effects on incident acute kidney injury are unknown. The study objective was to determine whether contrast administration within the first 24 hours was associated with acute kidney injury in survivors of sudden cardiac arrest. METHODS: This cohort study, derived from a prospective clinical trial, included patients with sudden cardiac arrest who survived for 48 hours, had no history of end-stage renal disease, and had at least 2 serum creatinine measurements during hospitalization. The contrast group included patients with exposure to iodinated contrast within 24 hours of sudden cardiac arrest. Incident acute kidney injury and first-time dialysis were compared between contrast and no contrast groups and then controlled for known acute kidney injury risk factors. RESULTS: Of the 199 survivors of sudden cardiac arrest, 94 received iodinated contrast. Mean baseline serum creatinine level was 1.3 mg/dL (95% confidence interval [CI] 1.4 to 1.5 mg/dL) for the contrast group and 1.6 mg/dL (95% CI 1.4 to 1.7 mg/dL) for the no contrast group. Incident acute kidney injury was lower in the contrast group (12.8%) than the no contrast group (17.1%; difference 4.4%; 95% CI -9.2% to 17.5%). Contrast administration was not associated with significant increases in incident acute kidney injury within quartiles of baseline serum creatinine level or after controlling for age, sex, race, congestive heart failure, diabetes, and admission serum creatinine level by regression analysis. Older age was independently associated with acute kidney injury. CONCLUSION: Despite elevated baseline serum creatinine level in most survivors of sudden cardiac arrest, iodinated contrast administration was not associated with incident acute kidney injury even when other acute kidney injury risk factors were controlled for. Thus, although acute kidney injury is not uncommon among survivors of sudden cardiac arrest, early (<24 hours) contrast administration from imaging procedures did not confer an increased risk for acute kidney injury. PMID- 26363572 TI - A hospital based surveillance system to assess the burden of trauma in KwaZulu Natal Province South Africa. AB - INTRODUCTION: In response to the ongoing excessive burden of trauma in South Africa the Data Management and Epidemiology Units of the Department of Health in conjunction with a group of trauma specialists developed a number of trauma data variables for inclusion on the routine District Health Information System (DHIS). The aim of this study is to describe the process followed and review the 2012 2014 data. METHODOLOGY: The variables collected included: total patient numbers assessed in the emergency room with a diagnosis of trauma; the mechanisms of trauma (blunt assault, motor vehicle accident, pedestrian vehicle accident, stab, gunshot wound, other); any trauma patient admitted to a health facility ward/ICU for longer than 12h; and whether the patient required transfer to a higher centre of care. All trauma deaths in hospital were recorded. The severity of trauma was measured using the Emergency Medical Services (EMS) classification of blue code (dead), red code (stretcher case with deranged physiology), yellow code (stretcher case with normal physiology) and green code (able to walk with normal physiology. The DHIS trauma data from April 2012 to March 2014 was reviewed. RESULTS: There were 197,219 emergency room visits for trauma in KZN in the 2013/2014 financial year. This constitutes 27.0% of all emergency room visits. The ratio of intentional to non-intentional injury is 45:55. There were 18,716 admissions to public sector hospitals for trauma in KZN in the 2013/2014 financial year. This constitutes 2.4% of all admissions in the province. There were 1045 inpatient deaths due to trauma in the same period, constituting 2.5% of all inpatient deaths. The overall rate of trauma in KZN was 17 per 1000 population. CONCLUSION: The adapted DHIS has successfully collected essential data that quantify the hospital burden of trauma in KZN province. This has provided the most complete overview of the burden of trauma in the Province. These trauma indicators should remain a permanent part of the DHIS to allow planners to track the trauma epidemic and to institute informed management strategies. PMID- 26363574 TI - The Effect of a Bone Tunnel During Ligament Reconstruction for Trapeziometacarpal Osteoarthritis: A 5-Year Follow-up. AB - PURPOSE: To compare in trapeziometacarpal (TMC) osteoarthritis the effects of trapeziectomy with tendon interposition and ligament reconstruction (LRTI) with or without a bone tunnel after a mean follow-up of 5 years. METHODS: We randomized 79 women (aged 40 years or older) with stage IV TMC osteoarthritis to either trapeziectomy with LRTI using a bone tunnel (Burton-Pellegrini) or a tendon sling arthroplasty (Weilby). Before surgery and at 3 months and 1 year after surgery, patients were evaluated for pain, function, strength, satisfaction, and complications. Of these patients, 72% were evaluated after a mean follow-up of 5 years (range, 3.8-6.4 years). RESULTS: There were no significant differences in function and pain (Patient-Rated Wrist and Hand Evaluation) between treatment groups after a mean follow-up of 5 years. In addition, grip and pinch strength, satisfaction, and persisting complications did not differ between groups. Three patients in the Weilby group had repeat surgery (2 for symptomatic scaphotrapezoidal osteoarthritis and 1 elsewhere) and one in the Burton-Pellegrini group operated on again elsewhere. Furthermore, 3 patients who were first conservatively treated for a trigger finger or neuroma were operated on again because conservative therapy failed. Two more patients were operated on again because of de Quervain tendinitis and carpal tunnel syndrome. The overall treatment effect of both groups together showed no significant differences between results at 1 and 5 years after surgery, except for grip strength, which improved for both groups. CONCLUSIONS: This study showed that improved function, strength, and satisfaction obtained at 1 year after trapeziectomy with LRTI with or without the use of a bone tunnel for stage IV TMC thumb osteoarthritis was maintained after 5 years. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic I. PMID- 26363573 TI - Clinical comparison of two different plating methods in minimally invasive plate osteosynthesis for clavicular midshaft fractures: A randomized controlled trial. AB - AIM: The aim of this study was to compare the clinical and radiographic outcomes between two different plating methods (superior vs. anteroinferior) in minimally invasive plate osteosynthesis (MIPO) for acute displaced clavicular shaft fractures. MATERIALS AND METHODS: A prospective, randomized controlled trial was performed in a single centre. Nineteen patients were treated with superior plating and 18 with anteroinferior plating using the MIPO technique. A 3.5-mm locking reconstruction plate was bent preoperatively and applied to either the anteroinferior or superior aspect of the clavicle through two separate incisions. The operating time, time to union, the proportional length difference, complications, and functional outcome of the shoulder joint were evaluated using the Constant score and the University of California Los Angeles (UCLA) score. RESULTS: There was no statistically significant difference in the Constant score and UCLA score. The mean time to union was 16.8 weeks for superior plating and 17.1 weeks for anteroinferior plating (p=0.866). The average operation time was 77.2min in superior plating and 79.4min in anteroinferior plating (p=0.491). One patient in the superior plating group showed plate failure. Despite no significant difference, one patient had nonunion in the superior plating group (p>0.999). CONCLUSIONS: From a clinical perspective, although MIPO with anteroinferior plating provides better outcomes especially in complications without statistically significant difference, both plating methods provided satisfactory clinical and radiographic outcomes. LEVEL OF EVIDENCE: Level I, a single-centre, prospective, randomized controlled trial. PMID- 26363575 TI - [Importance of dyslipidaemia in cardiovascular disease: a point of view]. AB - The authors present their view on the prevention of cardiovascular diseases, accepting the European ESC/EAS guidelines. They consider that the aim of the lipid control, based on LDL-C goals, is essential for the prevention and treatment of cardiovascular diseases. In subjects with metabolic syndrome (mainly, abdominal obesity, pre-diabetes and diabetes), the primary objective should be apoB or Non-HDL-C, which are better associated with cardiovascular risk. The treatment must be lifestyle changes and control of other risk factors. After calculating cardiovascular risk, statins are the first therapeutic step, with the strength and dose needed to achieve LDL-C goals. If targets are not achieved, ezetimibe or resins should be added. A new group of potent cholesterol lowering agents, the PCSK-9 monoclonal antibodies, have recently been approved in Spain. Subjects at very high cardiovascular risk that have achieved LDL-C goals, or other objectives (apoB, Non-HDL-C), other drugs (fibrates, omega-3) capable of modifying triglycerides and HDL-C could be added, if necessary. Treatment to reduce cardiovascular risk and prevent cardiovascular disease has proven effective in all populations and at all age groups. Subjects older than 80years should be individually assessed, taking into consideration possible comorbidities. PMID- 26363576 TI - Afferent hyperexcitability in neuropathic pain and the inconvenient truth about its degeneracy. AB - Neuropathic pain, which arises from damage to the nervous system, is a major unmet clinical challenge. Reversing the neuronal hyperexcitability induced by nerve damage is a logical treatment strategy but has proven frustratingly difficult. Here, we propose a novel explanation for that difficulty. Changes in several different ion channels are individually sufficient to cause hyperexcitability in primary somatosensory neurons. Despite offering multiple drug targets, this scenario is problematic: if multiple sufficient changes are triggered by nerve injury, then no single change is necessary for hyperexcitability. This so-called degeneracy compromises therapeutic interventions because drug effects on any one ion channel can be circumvented by changes occurring in other ion channels. Overcoming degeneracy demands a more integrative approach to drug discovery. PMID- 26363577 TI - Self-reported obstructive sleep apnea, simple snoring, and various markers of sleep-disordered breathing as predictors of cardiovascular risk. AB - PURPOSE: Our objective was to investigate whether self-reported obstructive sleep apnea (OSA), simple snoring, and various markers of sleep-disordered breathing (SDB) are associated with cardiovascular risk. METHODS: We examined a representative nationwide cohort of 5177 Finnish adults aged >=30 years. The participants underwent measurement of traditional cardiovascular risk factors and answered SDB-related questions derived from the Basic Nordic Sleep Questionnaire, which were used to operationalize self-reported OSA. The primary end point was incidence of a cardiovascular event (cardiovascular mortality, non-fatal myocardial infarction, non-fatal stroke, hospitalization for heart failure, or coronary interventions). RESULTS: During a median follow-up of 11.2 years and 52,910 person-years of follow-up, 634 participants suffered a cardiovascular event. In multivariable-adjusted Cox models, self-reported OSA (hazard ratio [HR] 1.34; 95 % confidence interval [CI] 1.04-1.73; p = 0.03) was an independent predictor of cardiovascular events. Self-reported simple snoring by itself was not associated with future cardiovascular events (HR 0.88 versus non-snorers, 95 % CI 0.75-1.04, p = 0.15). However, among snorers (n = 3152), frequent breathing cessations (HR 2.19, 95 % CI 1.26-3.81, p = 0.006) and very loud and irregular snoring (HR 1.82, 95 % CI 1.31-2.54, p < 0.001) were associated with cardiovascular risk. CONCLUSIONS: Self-reported OSA and SDB-related snoring variables are associated with cardiovascular risk, whereas simple snoring is not. In clinical practice and in surveys, questions concerning only habitual snoring should be amended with questions focusing on respiratory pauses and snoring stertorousness, which can be used to estimate the risk of OSA and cardiovascular events. PMID- 26363579 TI - The neural basis of one's own conscious and unconscious emotional states. AB - The study of emotional states has recently received considerable attention within the cognitive and neural sciences. However, limited work has been done to synthesize this growing body of literature within a coherent hierarchical, neuro cognitive framework. In this article, we review evidence pertaining to three interacting hierarchical neural systems associated with the generation, perception and regulation of one's own emotional state. In the framework we propose, emotion generation proceeds through a series of appraisal mechanisms - some of which appear to require more cognitively sophisticated computational processing (and hence more time) than others - that ultimately trigger iterative adjustments to one's bodily state (as well as to the modes of processing in other cognitive systems). Perceiving one's own emotions then involves a multi-stage interoceptive/somatosensory process by which these body state patterns are detected and assigned conceptual emotional meaning. Finally, emotion regulation can be understood as a hierarchical control system that, at various levels, modulates autonomic reactions, appraisal mechanisms, attention, the contents of working memory, and goal-directed action selection. We highlight implications this integrative model may have for competing theories of emotion and emotional consciousness and for guiding future research. PMID- 26363578 TI - Weighted STOP-Bang and screening for sleep-disordered breathing. AB - BACKGROUND: STOP-Bang is a tool for predicting the likelihood for sleep disordered breathing (SDB). In the conventional score, all variables are dichotomous. Our aim was to identify whether modifying the STOP-Bang scoring tool by weighting the variables could improve test characteristics. METHODS: Subjects who participated in the Sleep Heart Health Study (SHHS) were included in this analysis using a derivation dataset (n = 1667) and a validation dataset (n = 4774). In the derivation dataset, each STOP-Bang variable was evaluated using linear regression against the presence of SDB (AHI > 15/h) in order to determine the coefficients that would allow variable weighting. In other models, BMI, age, and neck circumference were entered as continuous variables. The sum of the weighted dichotomous variables yielded a weighted STOP-Bang (wSTOP-Bang). The sum of the weighted-continuous variables yielded a continuous STOP-Bang (cSTOP-Bang). The wSTOP-Bang, cSTOP-Bang, and the conventional STOP-Bang scores were then applied to the validation dataset, and receiver operating characteristic (ROC) curves were constructed. RESULTS: The area under the curve (AUC) for cSTOP-Bang (0.738) was greater than the AUC for conventional STOP-Bang (0.706) and wSTOP Bang (0.69). The sensitivities for cSTOP-Bang, STOP-Bang, and wSTOP-Bang were similar at 93.2, 93.2, and 93.3 %, respectively. The cSTOP-Bang had a higher specificity (31.8 %) than both STOP-Bang (23.2 %) and wSTOP-Bang (23.6 %). The cSTOP-Bang had a higher likelihood ratio of a positive test (1.36) than both STOP Bang (1.21) and wSTOP-Bang (1.22). CONCLUSIONS: Modifying the STOP-Bang score by weighting the variables and using continuous variables for BMI, age, and neck circumference can maintain sensitivity while improving specificity, positive likelihood ratio, and area under the receiver operating characteristic curve. PMID- 26363580 TI - Early results of a novel technique: Hindfoot fusion in talus osteonecrosis prior to ankle arthroplasty: A case series. AB - BACKGROUND: The purpose of this study was to evaluate the clinical outcome of a two staged approach of subtalar arthrodesis followed by TAR for patients with ankle arthritis and AVN talus. METHODS: Out of total 210 TARs performed at our institute; 7 patients underwent a two staged procedure between 2006 and 2010. All patients had over 3 years of follow up (except one). The clinical results were assessed using AOFAS, WOMAC, SF-36 and patient satisfaction scores. RESULTS: The mean follow up was 3 years. There was significant improvement in AOFAS and WOMAC (pain and stiffness) from pre-op to 3 years post-op (P<0.05). SF 36 scores improved from pre-op to 3 years post-op for 6/8 domains. 5 patients were satisfied at 3 years for overall surgical outcomes, 4 were satisfied with pain relief. Radiological signs of talar subsidence were noted in 2 patients at year 1. This did not progress at 3 years and did not deteriorate clinical outcome. CONCLUSION: We recommend our two staged approach to deal with this difficult clinical problem. We believe this approach is safe for TAR surgery where talar vascularity and bone quality is questionable leading to reduced talar subsidence, ischaemic pain and improvement in longevity of TAR. LEVEL OF EVIDENCE: Evidence IV (Retrospective case series). PMID- 26363581 TI - An alternative solution for computer controlled tuning and matching of existing NMR probes. AB - Tuning and matching of NMR probes is necessary for many fields of NMR application including temperature dependent NMR, thermoporometry and cryoporometry, or when significantly different types of samples are measured in automation using sample changers. Mismatch of the probe is an especially critical issue in the case of high magnetic fields, polar or ionic solvents, or extreme thermal conditions. Careful tuning is particularly important for quantitative NMR measurements. Manual tuning and matching of the NMR probe is not possible in the case of automated or remotely controlled measurements. Spectrometer manufacturers offer modern probes equipped with automatic tuning/matching mechanics, like Bruker ATMTM, suitable for these experiments. The disadvantages of probes with built-in ATMTM are the significantly higher price, and the non-detachable and non-portable construction. Computer controlled tuning and matching is highly desirrable in solid state NMR since no industrial solution has been developed yet for MAS NMR probes. We present an alternative solution for computer controlled tuning and matching of existing Bruker probes. Building costs are significantly lower, since only commercially available components and ICs are used. PMID- 26363582 TI - High-resolution NMR of hydrogen in organic solids by DNP enhanced natural abundance deuterium spectroscopy. AB - We demonstrate that high field (9.4 T) dynamic nuclear polarization (DNP) at cryogenic (~100 K) sample temperatures enables the rapid acquisition of natural abundance (1)H-(2)H cross-polarization magic angle spinning (CPMAS) solid-state NMR spectra of organic solids. Spectra were obtained by impregnating substrates with a solution of the stable DNP polarizing agent TEKPol in tetrachloroethane. Tetrachloroethane is a non-solvent for the solids, and the unmodified substrates are then polarized through spin diffusion. High quality natural abundance (2)H CPMAS spectra of histidine hydrochloride monohydrate, glycylglycine and theophylline were acquired in less than 2h, providing direct access to hydrogen chemical shifts and quadrupolar couplings. The spectral resolution of the (2)H solid-state NMR spectra is comparable to that of (1)H spectra obtained with state of the art homonuclear decoupling techniques. PMID- 26363584 TI - Faster and cleaner real-time pure shift NMR experiments. AB - Real-time pure shift experiments provide highly resolved proton NMR spectra which do not require any special processing. Although being more sensitive than their pseudo 2D counterparts, their signal intensities per unit time are still far below regular NMR spectra. In addition, scalar coupling evolution during the individual data chunks produces decoupling sidebands. Here we show that faster and cleaner real-time pure shift spectra can be obtained through the implementation of two parameter alterations. Variation of the FID chunk lengths between individual transients significantly suppresses decoupling sidebands for any kind of real-time pure shift spectra and thus allows for example the analysis of minor components in compound mixtures. Shifting the excitation frequency between individual scans of real-time slice-selective pure shift spectra increases their sensitivity obtainable in unit time by allowing faster repetitions of acquisitions. PMID- 26363583 TI - Correcting surface coil excitation inhomogeneities in single-shot SPEN MRI. AB - Given their high sensitivity and ability to limit the field of view (FOV), surface coils are often used in magnetic resonance spectroscopy (MRS) and imaging (MRI). A major downside of surface coils is their inherent radiofrequency (RF) B1 heterogeneity across the FOV, decreasing with increasing distance from the coil and giving rise to image distortions due to non-uniform spatial responses. A robust way to compensate for B1 inhomogeneities is to employ adiabatic inversion pulses, yet these are not well adapted to all imaging sequences - including to single-shot approaches like echo planar imaging (EPI). Hybrid spatiotemporal encoding (SPEN) sequences relying on frequency-swept pulses provide another ultrafast MRI alternative, that could help solve this problem thanks to their built-in heterogeneous spatial manipulations. This study explores how this intrinsic SPEN-based spatial discrimination, could be used to compensate for the B1 inhomogeneities inherent to surface coils. Experiments carried out in both phantoms and in vivo rat brains demonstrate that, by suitably modulating the amplitude of a SPEN chirp pulse that progressively excites the spins in a direction normal to the coil, it is possible to compensate for the RF transmit inhomogeneities and thus improve sensitivity and image fidelity. PMID- 26363585 TI - SCI Longitudinal Aging Study: 40 Years of Research. AB - BACKGROUND: The Spinal Cord Injury (SCI) Longitudinal Aging Study was initiated in 1973 and has conducted 8 assessments over the past 40 years. It was designed to help rehabilitation professionals understand the life situation of people with SCI, but it has developed into the most long-standing study of aging and SCI and has resulted in over 50 publications. OBJECTIVE: Our purpose was to provide a detailed history of the study, response patterns, utilization of measures, and a summary of key findings reported in the literature. METHODS: Five participant samples have been incorporated over the 40 years, with enrollment in 1973, 1984, 1993 (2 samples), and 2003. A total of 2,208 participants have completed 6,001 assessments, with a particularly large number of assessments among those who are more than 40 years post injury (n = 349). RESULTS: The overall results have indicated changing patterns of outcomes over time as persons with SCI age, with some notable declines in participation and health. There has been a survivor effect whereby persons who are more active, well-adjusted, and healthier live longer. CONCLUSIONS: This study has several important features that are required for longitudinal research including (a) consistency of follow-up, (b) consistency of measures over time, (c) addition of new participant samples to counteract attrition, and (d) inclusion of a large number of individuals who have reached aging milestones unparalleled in the literature. Data from this study can inform the literature on the natural course of aging with SCI. PMID- 26363586 TI - Injuries and Falls in an Aging Cohort with Spinal Cord Injury: SCI Aging Study. AB - BACKGROUND: Limited research suggests that additional "subsequent" injuries occur frequently among persons with an existing spinal cord injury (SCI), which may result in further significant complications and added disability. OBJECTIVE: The purpose of this study was to (a) report the 12-month incidence of injuries by age in an aging SCI cohort, (b) report the 12-month incidence of falls, (c) assess the impact of injuries on participation by age, and (d) assess the relationship of age with injuries and falls while controlling for potential confounding factors. METHODS: Participants (N = 759) responded to questions about injuries and falls resulting in injury in the past year. Demographic and SCI characteristics, binge drinking, and prescription medication use were measured. RESULTS: A total of 19.2% reported 1 or more injuries in the past year, and 10.4% reported a fall resulting in an injury in the past year. Among those who sustained 1 or more injuries, 22.8% had at least 1 hospitalization for an injury within the past 12 months. Additionally, 47.6% were limited in their normal daily activities for a week or more due to injury. Prescription medication use was associated with injury in the past year and falls resulting in injury. Equal time between walking and wheelchair use as the primary mode of locomotion was also associated with falls in the past year. CONCLUSIONS: Future research should investigate circumstances surrounding subsequent injuries to aid in prevention efforts. Additionally, information is needed on whether subsequent injuries further contribute to physical disability. PMID- 26363587 TI - Impact of Marital Status on 20-Year Subjective Well-being Trajectories. AB - BACKGROUND: It is well-known that marital status has a significant impact on subjective well-being (SWB). However, research examining the long-term influence of marital status on SWB after spinal cord injury (SCI) is limited. OBJECTIVE: To identify the relationship between marital status and SWB trajectories over time, using 20 years of longitudinal data. METHODS: We conducted a cohort study, including 1,032 participants surveyed 5 times in 1993, 1998, 2003, 2008, and 2013. Participants were identified from outpatient records of 2 Midwestern hospitals and 1 Southeastern specialty hospital. The Life Situation Questionnaire Revised (LSQ-R) was used to measure multiple aspects of SWB. A multilevel model was applied to analyze the 5 repeated measurements. RESULTS: The married or cohabitating participants enjoyed the best SWB at baseline, but their home satisfaction and global satisfaction declined over time and their social isolation increased slightly. For divorced, separated, or widowed people, the negative effects of marital loss attenuated over time. For single individuals, SWB, except for environmental barriers, did not change positively over time if they remained single. CONCLUSIONS: Using longitudinal data with 5 repeated measurements, our study showed a complicated relationship between marital and relationship status with SWB and how these relationships change over time for people with chronic SCI. PMID- 26363588 TI - Aging and Spinal Cord Injury: External Causes of Injury and Implications for Prevention. AB - BACKGROUND: Despite a consistent trend toward older age at time of spinal cord injury (SCI), little is known about the external causes of SCI in the elderly. OBJECTIVE: To examine environmental circumstances, documented by International Classification of Diseases, 10th Revision, Clinical Modification codes, at time of SCI among older adults. METHODS: Data on individuals injured in 2005 or later were retrieved from the National SCI Database. Demographics, injury profiles, and external causes of injury were compared between the study group (age >60 years, n = 1,079) and reference group (age 16-45 years, n = 3,579) using chi-square and Student t tests. RESULTS: Among the elderly, falls were the most common etiology of SCI (60%), followed by transport accidents (24%) and complications of medical and surgical care (12%). In the younger group, transport accidents were the most common etiology of SCI (49%), followed by falls (22%) and assault (21%). Falls on the same level (30%), from stairs and steps (22%), and other slipping, tripping, and stumbling (11%) were the most common mechanisms of falls in the elderly group. Among motor vehicle accidents, car occupant injured in a collision with another car was the most common mechanism of injury among the elderly (28%). CONCLUSIONS: There is an urgent need for effective fall prevention programs among the elderly to reduce SCI in this expanding population. Details on the mechanisms of falls and other major causes of SCI among the elderly provided in this study should inform the development of future interventions for high-risk persons, activities, and environments. PMID- 26363589 TI - Sexual Function, Satisfaction, and Use of Aids for Sexual Activity in Middle-Aged Adults with Long-Term Physical Disability. AB - BACKGROUND: Sexuality is an important aspect of quality of life in individuals with disabilities, yet little is known about what factors contribute to sexual satisfaction as these individuals age. METHODS: Middle-aged adults with physical disabilities completed a cross-sectional survey that included measures of sexual activity, function, and satisfaction. RESULTS: Consistent with studies of able bodied adults, sexual function was the strongest predictor of satisfaction. However, depression also predicted sexual satisfaction for women. Use of aids for sexual activity varied by disability type and was generally associated with better function. Lowest levels of sexual satisfaction were reported by men with SCI. CONCLUSIONS: Depression may negatively impact sexual satisfaction in women, beyond contributions of sexual dysfunction, and effective use of sexual aids may improve function in this population. PMID- 26363590 TI - Participation and Life Satisfaction in Aged People with Spinal Cord Injury: Does Age at Onset Make a Difference? AB - BACKGROUND: Few studies have reported on outcomes in samples of elderly people with SCI and the impact of the age at onset of SCI is unclear. OBJECTIVE: To study levels of participation and life satisfaction in individuals with SCI aged 65 years or older and to analyze differences in participation and life satisfaction scores between individuals injured before or after 50 years of age. METHODS: This cross-sectional survey included 128 individuals with SCI who were at least 65 years old. Age at onset was dichotomized as <50 or >= 50 years of age. Participation was measured with the Frequency scale of the Utrecht Scale for Evaluation-Participation, and life satisfaction was measured with 5 items of the World Health Organization Quality of Life abbreviated form. RESULTS: Participants who were injured before 50 years of age showed similar levels of functional status and numbers of secondary health conditions but higher participation and life satisfaction scores compared to participants injured at older age. In the multiple regression analysis of participation, lower current age, higher education, and having paraplegia were significant independent determinants of increased participation (explained variance, 25.7%). In the regression analysis of life satisfaction, lower age at onset and higher education were significant independent determinants of higher life satisfaction (explained variance, 15.3%). CONCLUSIONS: Lower age at onset was associated with better participation and life satisfaction. This study did not reveal indications for worsening participation or life satisfaction due to an accelerated aging effect in this sample of persons with SCI. PMID- 26363591 TI - Reliability and Validity of the Sensory Component of the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI): A Systematic Review. AB - BACKGROUND: Since 1982, the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) has been used to classify sensation of spinal cord injury (SCI) through pinprick and light touch scores. The absence of proprioception, pain, and temperature within this scale creates questions about its validity and accuracy. OBJECTIVE: To assess whether the sensory component of the ISNCSCI represents a reliable and valid measure of classification of SCI. METHODS: A systematic review of studies examining the reliability and validity of the sensory component of the ISNCSCI published between 1982 and February 2013 was conducted. The electronic databases MEDLINE via Ovid, CINAHL, PEDro, and Scopus were searched for relevant articles. A secondary search of reference lists was also completed. Chosen articles were assessed according to the Oxford Centre for Evidence-Based Medicine hierarchy of evidence and critically appraised using the McMasters Critical Review Form. A statistical analysis was conducted to investigate the variability of the results given by reliability studies. RESULTS: Twelve studies were identified: 9 reviewed reliability and 3 reviewed validity. All studies demonstrated low levels of evidence and moderate critical appraisal scores. The majority of the articles (~67%; 6/9) assessing the reliability suggested that training was positively associated with better posttest results. The results of the 3 studies that assessed the validity of the ISNCSCI scale were confounding. CONCLUSIONS: Due to the low to moderate quality of the current literature, the sensory component of the ISNCSCI requires further revision and investigation if it is to be a useful tool in clinical trials. PMID- 26363592 TI - Neurogenic Bladder and Urodynamic Outcomes in Patients with Spinal Cord Myelopathy. AB - BACKGROUND: Urodynamics (UDs) are routine in traumatic spinal cord injury (SCI), but there are few reports regarding nontraumatic spinal cord myelopathy (SCM) patients. PURPOSE: To describe the neurogenic bladder and UD outcomes in SCM patients and determine whether the UD recommendations result in clinically important changes to bladder management. METHODS: This retrospective case study examined a series of SCM patients admitted to a spinal rehabilitation service who underwent UDs between January 1, 2000 and June 30, 2010. RESULTS: Sixty-five UD tests were performed a median of 7 months post SCM. Most (n = 34; 57%) patients were male, and the median age was 60 years. Most patients (n = 46; 77%) were paraplegic and were continent of urine (n = 38; 58%). Thirty-five (46%) patients voided on sensation, 26 (40%) performed intermittent self-catheterization, and 9 (14%) had an indwelling catheter. The most common UD finding was overactive detrusor with no dysynergia (n = 31; 48%), followed by overactive detrusor with sphincter dysynergia (n = 16; 25%) and detrusor areflexia/underactive (n = 12; 18%). Key UD findings were median cystometric capacity 414 mL (interquartile range [IQR], 300-590), median maximum detrusor contraction 49.5 cmH2O (IQR, 25 85), and median residual volume post voiding 100 mL (IQR, 5-200). The recommendations for changes to bladder management following UDs resulted in clinically important changes to existing strategies in 57 studies (88%). CONCLUSIONS: Future studies should ascertain whether our screening protocol is appropriate, and a longer-term follow-up should examine the relationship between UD recommendations and prevention of complications. PMID- 26363593 TI - Assessment of Attention to Clothing and Impact of Its Restrictive Factors in Iranian Patients with Traumatic Spinal Cord Injury (ACIRF-SCI): Introduction of a New Questionnaire. AB - BACKGROUND: Patients with spinal cord injury (SCI) deal with various restrictive factors regarding their clothing, such as disability and difficulty with access to shopping centers. OBJECTIVE: We designed a questionnaire to assess attention to clothing and impact of its restrictive factors among Iranian patients with SCI (ACIRF-SCI). METHODS: The ACIRF-SCI has 5 domains: functional, medical, attitude, aesthetic, and emotional. The first 3 domains reflect the impact of restrictive factors (factors that restrict attention to clothing), and the last 2 domains reflect attention to clothing and fashion. Functional restrictive factors include disability and dependence. Medical restrictive factors include existence of specific medical conditions that interfere with clothing choice. Construct validity was assessed by factorial analysis, and reliability was expressed by Cronbach's alpha. RESULTS: A total of 100 patients (75 men and 25 women) entered this study. Patients with a lower injury level had a higher total score (P < .0001), and similarly, patients with paraplegia had higher scores than those with tetraplegia (P < .0001), which illustrates an admissible discriminant validity. Postinjury duration was positively associated with total scores (r = 0.21, P = .04). Construct validity was 0.97, and Cronbach's alpha was 0.61. CONCLUSIONS: Iranian patients with SCI who have greater ability and independence experience a lower impact of restrictive factors related to clothing. The ACIRF-SCI reveals that this assumption is statistically significant, which shows its admissible discriminant validity. The measured construct validity (0.97) and reliability (internal consistency expressed by alpha = 0.61) are acceptable. PMID- 26363596 TI - Geometry: a secret weapon in the fight against viruses. PMID- 26363597 TI - A call for us all to resist the resistance. PMID- 26363599 TI - Treatment of a mastoid defect by free anterolateral thigh flap. AB - INTRODUCTION: Free anterolateral thigh (ALT) flap constitutes an alternative to latissimus dorsi and radial forearm flaps for head and neck reconstruction. The authors report a case of mastoid reconstruction in a patient with multi-operated cholesteatoma associated with tubal dysfunction. CASE REPORT: This patient presented a fistula of the lateral semicircular canal and invagination of retroauricular soft tissues responsible for non-compensated almost complete areflexia with anacusis. She did not present any signs of cholesteatoma recurrence, but chronic inflammation of the mastoidectomy cavity. The head and neck procedure consisted of translabyrinthine labyrinthectomy: resection of the atrophic retroauricular skin, resection of the vestibular neurosensory tissue and obliteration of the mastoidectomy cavity. An ALT flap measuring 5*5 cm, anastomosed to the superior thyroid artery and facial vein, was used to cover the defect. Careful defatting of the flap allowed filling of the defect, while providing a sufficient quantity of appropriate tissue. The postoperative course was uneventful and the patient was considerably improved. The only donor site sequelae consisted of a thin linear scar. CONCLUSION: The free anterolateral thigh flap, a reliable, polyvalent flap that can be shaped as needed and which is associated with minimal donor site morbidity, constitutes a good alternative for head and neck reconstruction. PMID- 26363598 TI - Insights into the Genetic Susceptibility to Type 2 Diabetes from Genome-Wide Association Studies of Obesity-Related Traits. AB - Obesity and type 2 diabetes (T2D) are common and complex metabolic diseases, which are caused by an interchange between environmental and genetic factors. Recently, a number of large-scale genome-wide association studies (GWAS) have improved our knowledge of the genetic architecture and biological mechanisms of these diseases. Currently, more than ~250 genetic loci have been found for monogenic, syndromic, or common forms of T2D and/or obesity-related traits. In this review, we discuss the implications of these GWAS for obesity and T2D, and investigate the overlap of loci for obesity-related traits and T2D, highlighting potential mechanisms that affect T2D susceptibility. PMID- 26363600 TI - Speech perception, production and intelligibility in French-speaking children with profound hearing loss and early cochlear implantation after congenital cytomegalovirus infection. AB - OBJECTIVE: To analyze speech in children with profound hearing loss following congenital cytomegalovirus (cCMV) infection with cochlear implantation (CI) before the age of 3 years. MATERIAL AND METHODS: In a cohort of 15 children with profound hearing loss, speech perception, production and intelligibility were assessed before and 3 years after CI; variables impacting results were explored. RESULTS: Post-CI, median word recognition was 74% on closed-list and 48% on open list testing; 80% of children acquired speech production; and 60% were intelligible for all listeners or listeners attentive to lip-reading and/or aware of the child's hearing loss. Univariate analysis identified 3 variables (mean post-CI hearing threshold, bilateral vestibular areflexia, and brain abnormality on MRI) with significant negative impact on the development of speech perception, production and intelligibility. CONCLUSION: CI showed positive impact on hearing and speech in children with post-cCMV profound hearing loss. Our study demonstrated the key role of maximizing post-CI hearing gain. A few children had insufficient progress, especially in case of bilateral vestibular areflexia and/or brain abnormality on MRI. This led us to suggest that balance rehabilitation and speech therapy should be intensified in such cases. PMID- 26363601 TI - Extranodal non-Hodgkin lymphoma of the sinonasal cavities: A 22-case report. AB - OBJECTIVE: To determine presenting features, management and prognosis in extranodal non-Hodgkin lymphoma of the sinonasal tract. MATERIAL AND METHODS: A retrospective study between 2004 and 2013 in the University Hospital Center of Nantes (France) recruited patients with lymphoma discovered by sinonasal involvement. Epidemiologic, diagnostic, clinical and prognostic criteria were analyzed, with survival studied on the Kaplan-Meier estimator and Log-rank test. RESULTS: Twenty-two patients were included: 14 male, 7 female, with a mean age of 65 years at diagnosis. All had non-Hodgkin lymphoma, with strong predominance of diffuse large B-cell lymphoma (77%). Seven patients had risk factors for lymphoma (infection by HIV, EBV or chronic lymphocytic leukemia). A majority (68%) had advanced tumor at diagnosis (stage IV on the Ann Arbor classification). Most were located in the craniofacial bones (68%), mainly involving the maxillary or ethmoidal sinuses. The most frequent presenting symptoms were unilateral nasal obstruction, mucopurulent rhinorrhea, recurrent epistaxis or diplopia. Treatment consisted in chemotherapy, in some cases associated to radiotherapy. Overall survival was 82% at 12 months and 73% at 36 months. Recurrence-free survival was 76% at 12 months and 64% at 36 months. CONCLUSION: Lymphoma is an aggressive pathology; revelation by sinonasal involvement is rare. Recommended treatment is chemotherapy, possibly associated to radiotherapy. Prognosis depends on histologic type, Ann Arbor stage at diagnosis and the therapeutic options available for the individual patient. PMID- 26363602 TI - State of the art of endoscopic frontal sinus cerebrospinal fluid leak repair. AB - Frontal sinus cerebrospinal fluid leaks are rare and their surgical management is difficult. Up until recently, they could only be treated by open surgery with an osteoplastic flap. With the development of endoscopic surgery, less invasive techniques such as an exclusive endoscopic approach can now be used, ensuring a simpler postoperative course. However, these techniques require a thorough knowledge of frontal sinus anatomy and endoscopic CSF leak repair. This knowledge is essential both to ensure closure of the CSF leak and to preserve frontal sinus patency. PMID- 26363604 TI - How do midwives in Slovenia view their professional status? AB - OBJECTIVE: The aim of the study was to explore Slovenian midwives' views of their professional status. The influence of participants' educational background on their views was also examined, since higher education is related to professionalism. DESIGN: This was a quantitative descriptive survey, using postal data collection. The questionnaire comprised of six elements crucial for professionalism--three elements distinctive of 'old' professionalism (power, ethics, specific knowledge) and three characteristics of 'new' professionalism (reflective practice, inter-professional collaboration and partnership with users). PARTICIPANTS: A total of 300 midwives who were registered in a national register of nurses and midwives at the time of the study. The response rate was 50.7% (152 returned the questionnaire). Participants that were on a probationary period were excluded, leaving 128 questionnaires for analysis (43%). Some 40.9% participants had secondary midwifery education, 56.7% had higher midwifery education and only few (2.4%) finished postgraduate education. FINDINGS: The majority of participants did not consider midwifery to be a specific profession. Midwives with secondary education were more likely to consider practical skills to be important than theoretical midwifery knowledge. In general midwives did not feel enabled to practice autonomously; and this caused them to face ethical dilemmas when aiming to fulfil women's wishes. All participants with midwifery secondary school education thought that obstetrics jeopardises midwifery scope of practice, but only half of the BSc participants thought this. One-fifth of all participants estimated that midwifery is also threatened by nursing. The respondents reported feeling a lack of control over their professional activity and policy making; however the majority of midwives claimed that they were willing to take on more responsibility for independent practice. KEY CONCLUSIONS: Slovenian midwifery cannot be considered to be a profession yet. It faces several hindrances, due to its historical development. IMPLICATIONS FOR PRACTICE: In order to develop a specific professional identity for midwives, the content and structure of education should be analysed and changed in order to improve socialisation and professionalism. In clinical settings, the scope of midwifery practice and responsibilities, as defined by EU directives, should be agreed by all professional groups. PMID- 26363603 TI - The origin of prostate metastases: emerging insights. AB - The outcome of patients with prostate cancer (PCa) is mainly dependent on the presence or absence of distant metastases. Although several advances have been made in understanding the biological basis of this tumor, the mechanisms underlying PCa metastatic spread are not fully clear. The lack of a clear origin for PCa metastasis may be partially due to the evidence of PCa heterogeneity between primary tumor and metastases and among different metastatic sites. Cross metastatic seeding and the de novo monoclonal seeding of daughter metastases have been proposed as crucial events during metastasis. This process requires the contribution of tumor environment, which modulates cancer cell homing and growth, and involves several components including cancer stem cells (CSCs), tumor secreted microvesicles, circulating tumor cells (CTCs), and immune cells. In this review, we have focused on the recent findings on the origin of prostate metastasis, showing the contribution of tumor microenvironment to this evolutionary process. PMID- 26363605 TI - Suspect screening of large numbers of emerging contaminants in environmental waters using artificial neural networks for chromatographic retention time prediction and high resolution mass spectrometry data analysis. AB - The recent development of broad-scope high resolution mass spectrometry (HRMS) screening methods has resulted in a much improved capability for new compound identification in environmental samples. However, positive identifications at the ng/L concentration level rely on analytical reference standards for chromatographic retention time (tR) and mass spectral comparisons. Chromatographic tR prediction can play a role in increasing confidence in suspect screening efforts for new compounds in the environment, especially when standards are not available, but reliable methods are lacking. The current work focuses on the development of artificial neural networks (ANNs) for tR prediction in gradient reversed-phase liquid chromatography and applied along with HRMS data to suspect screening of wastewater and environmental surface water samples. Based on a compound tR dataset of >500 compounds, an optimized 4-layer back-propagation multi-layer perceptron model enabled predictions for 85% of all compounds to within 2min of their measured tR for training (n=344) and verification (n=100) datasets. To evaluate the ANN ability for generalization to new data, the model was further tested using 100 randomly selected compounds and revealed 95% prediction accuracy within the 2-minute elution interval. Given the increasing concern on the presence of drug metabolites and other transformation products (TPs) in the aquatic environment, the model was applied along with HRMS data for preliminary identification of pharmaceutically-related compounds in real samples. Examples of compounds where reference standards were subsequently acquired and later confirmed are also presented. To our knowledge, this work presents for the first time, the successful application of an accurate retention time predictor and HRMS data-mining using the largest number of compounds to preliminarily identify new or emerging contaminants in wastewater and surface waters. PMID- 26363606 TI - Gender differences in farmers' responses to climate change adaptation in Yongqiao District, China. AB - This study examines the gender differences in farmers' responses to climate change adaption in Yongqiao District, China. A random sampling technique was used to select 220 household heads, while descriptive statistics and binary logit models were used to analyze the data obtained from the households. We determine that male and female respondents are not significantly different in their knowledge and perceptions of climate change, but there is a gender difference in adopting climate change adaptation measures. Male-headed households are more likely to adopt new technology for water conservation and to increase investment in irrigation infrastructure. The research also indicates that the adaptation decisions of male and female heads are influenced by different sets of factors. The findings of this research help to elucidate the determinants of climate change adaptation decisions for male and female-headed households and the strategic interventions necessary for effective adaptation. PMID- 26363607 TI - The effects of indoor and outdoor dust exposure on the growth, sensitivity to oxidative-stress, and biofilm production of three opportunistic bacterial pathogens. AB - Within the last decade, many studies have highlighted the radical changes in the components of indoor and outdoor dust. For example, agents like automobile emitted platinum group elements and different kinds of organic phthalates and esters have been reported to be accumulating in the biosphere. Humans consistently face dermal, respiratory, and dietary exposures to these particles while indoors and outdoors. In fact, dust particulate matter has been associated with close to 500,000 deaths per year in Europe and about 200,000 deaths per year in the United States. To date, there has been limited examination of the physiological impact of indoor and outdoor dust exposure on normal flora microbes. In this study, the effect of indoor- and outdoor-dust exposure on three opportunistic bacterial species (Escherichia coli, Enterococcus faecalis, and Pseudomonas aeruginosa) was assessed. Specifically, bacterial growth, oxidative stress resistance, and biofilm production were measured following indoor- and outdoor-dust exposures. Studies were conducted in nutritionally-rich and -poor environments typically encountered by bacteria. Surprisingly, indoor-dust (200MUg/mL), enhanced the growth of all three bacterial species in nutrient-poor conditions, but slowed growth in nutrient-rich conditions. In nutrient-rich medium, 100MUg/mL exposure of either indoor- or outdoor-dust resulted in significantly reduced oxidative stress resistance in E. coli. Most interestingly, dust (indoor and outdoor), either in nutrient-rich or -poor conditions, significantly increased biofilm production in all three bacterial species. These data suggest that indoor and outdoor dust, can modify opportunistic bacteria through altering growth, sensitivity to oxidative stress, and their virulence potential through enhanced biofilm formation. PMID- 26363608 TI - Occurrence and risk assessment of organophosphate esters in drinking water from Eastern China. AB - Organophosphate esters (OPEs) are ubiquitous in the environment and may pose potential health risks to humans. Drinking water is suspected as one possible exposure pathway of OPEs to humans. In this study, we investigated the residues of 9 OPEs in five types of drinking water in Eastern China. The median concentrations of Sigma9OPEs were determined to be 3.99, 4.50, 27.6, 59.2 and 192ng/L in the bottled, well, barreled, direct drinking and tap waters, respectively. Triethyl phosphate (TEP) was the most abundant OPE in the tap water and filtered drinking water with median concentrations of 50.2 and 30.2ng/L, respectively. The mixture of tri(chloropropyl) phosphate (TCPP) and tri(chloroisopropyl) phosphate (TCIPP), named here as TCPP, dominated in the barreled and well water with median concentrations of 8.04 and 2.49ng/L, respectively. The calculated average daily doses of OPEs ranged from 0.14 to 7.07ng/kgbw/day for people consuming the five different types of drinking water. Among the drinking water, the tap water exhibited the highest exposure doses of OPEs. The calculated non-cancer hazard quotients (10(-4)-10(-7)) from OPEs were much lower than the theoretical threshold of risk. The carcinogenic risks posed by TCEP were very low (<10(-7)) for all types of drinking water. The results revealed that there was currently low risk to human health from exposure to OPEs through drinking water in Eastern China. PMID- 26363609 TI - An assessment of current antenatal care practices and identification of modifiable risk factors for prematurity and low birth weight infants in pregnancy in Solomon Islands. PMID- 26363611 TI - Wild Help for Enhancing Genetic Resistance in Lentil Against Fungal Diseases. AB - Lentil (Lens culinaris) is one of the cool season grain legume crops and an important source of dietary proteins and fibre. Fungal diseases are main constraints to lentil production and account for significant yield and quality losses. Lentil has a narrow genetic base presumably due to a bottleneck during domestication and as a result, any resistance to fungal diseases in the cultivated genepool is gradually eroded and overcome by pathogens. New sources of resistance have been identified in wild lentil (Lens ervoides). This article provides an overview of harnessing resistance potential of wild germplasm to enhance genetic resistance in lentil cultivars using next-generation sequencing based genotyping, comparative genomics and marker-assisted selection breeding. PMID- 26363610 TI - Developmental changes in polyunsaturated fetal plasma phospholipids and feto maternal plasma phospholipid ratios and their association with bronchopulmonary dysplasia. AB - BACKGROUND: Docosahexaenoic (C22:6) and arachidonic acid (C20:4) are long-chain polyunsaturated fatty acids (LC-PUFA), essential to fetal development, and preferentially transported by plasma phospholipids. OBJECTIVE: To characterize fetal and maternal plasma phospholipid changes during gestation, and to investigate whether LC-PUFA phospholipid profiles are associated with bronchopulmonary dysplasia (BPD). DESIGN: Cord plasma and parturient serum from N = 108 pregnancies [24-42 week postmenstrual age (PMA)] were collected. Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were analyzed with tandem mass spectrometry. PMA-associated changes were quantified, and break point analyses served to describe nonlinear changes during gestation. RESULTS: PC and PE were lower in cord than in parturient samples. In parturients, PC decreased until 33 week PMA, but then re-increased, whereas in cord plasma, concentrations linearly decreased. Fetal PC and PC sub-group values correlated with maternal values. C20:4-PC was twofold higher in cord than in maternal samples throughout gestation. C22:6-PC values, however, exceeded maternal values only beyond 33 week PMA. Consequently, early preterm C20:4-PC-to-C22:6-PC ratio largely exceeded term infant values. In infants born before 28 week PMA, a low C20:4-PC-to-C22:6-PC ratio was associated with BPD severity. CONCLUSIONS: Fetal plasma LC-PUFA-PC composition correlates with maternal values. Fetal C20:4-PC exceeds maternal values throughout gestation, whereas C22:6-PC exceeds maternal values only beyond 33 week PMA, resulting in a low fetal C20:4-PC/C22:6-PC ratio only toward end gestation. A low C20:4-PC/C22:6-PC ratio before 28 week PMA is associated with BPD severity. These data point to a concept of PMA-adjusted ARA and DHA supplementation and, potentially, cord plasma phospholipid analysis for BPD prediction. PMID- 26363612 TI - Parental responsibility beliefs: associations with parental anxiety and behaviours in the context of childhood anxiety disorders. AB - BACKGROUND: High levels of parental anxiety are associated with poor treatment outcomes for children with anxiety disorders. Associated parental cognitions and behaviours have been implicated as impediments to successful treatment. We examined the association between parental responsibility beliefs, maternal anxiety and parenting behaviours in the context of childhood anxiety disorders. METHODS: Anxious and non-anxious mothers of 7-12 year old children with a current anxiety disorder reported their parental responsibility beliefs using a questionnaire measure. Parental behaviours towards their child during a stressor task were measured. RESULTS: Parents with a current anxiety disorder reported a greater sense of responsibility for their child's actions and wellbeing than parents who scored within the normal range for anxiety. Furthermore, higher parental responsibility was associated with more intrusive and less warm behaviours in parent-child interactions and there was an indirect effect between maternal anxiety and maternal intrusive behaviours via parental responsibility beliefs. LIMITATIONS: The sample was limited to a treatment-seeking, relatively high socio-economic population and only mothers were included so replication with more diverse groups is needed. The use of a range of stressor tasks may have allowed for a more comprehensive assessment of parental behaviours. CONCLUSIONS: The findings suggest that parental anxiety disorder is associated with an elevated sense of parental responsibility and may promote parental behaviours likely to inhibit optimum child treatment outcomes. Parental responsibility beliefs may therefore be important to target in child anxiety treatments in the context of parental anxiety disorders. PMID- 26363613 TI - Inflammation as a neurobiological substrate of cognitive impairment in bipolar disorder: Evidence, pathophysiology and treatment implications. AB - BACKGROUND: Bipolar disorder (BD) has been associated with cognitive impairment during depressed, manic and euthymic periods. Inflammation has been shown to be involved in the pathophysiology of BD and cognitive impairment. METHODS: For this systematic review, the MEDLINE/PubMed, Embase, Google Scholar and ClinicalTrials.gov databases were searched for relevant articles assessing the association between cognitive function and inflammatory markers in BD subjects. A discussion of potential mechanisms and therapeutic implications is also included to provide further context to the subject matter. RESULTS: Eight studies, including a total of 555 BD subjects, assessing the association between cognitive function and inflammatory markers were identified. Cognitive dysfunction was associated with elevated levels of pro-inflammatory markers YKL40, IL-6, sCD40L, IL-1Ra, hsCRP and TNF-alpha. Mechanistically, elevation in inflammatory cytokines alters monoamine levels leading to cognitive and affective dysfunction. Neuro inflammation, manifesting as microglial activation, leads to increased oxidative stress, pathologic synaptic pruning and impaired neuroplasticity in key brain regions sub-serving mood and cognition. Immune dysfunction also activates the hypothalamic-pituitary-adrenal (HPA) axis leading to hypercortisolemia and metabolic dysfunction, further promoting neuronal dysfunction. Anti-inflammatory agents are therefore currently being investigated in the treatment of BD and appear to exert an antidepressant effect; however, cognitive outcomes have yet to be reported. CONCLUSION: Several studies suggest that immune dysfunction is associated with cognitive impairment in BD. Several neurobiological pathways have been identified whereby immune dysfunction may promote cognitive impairment in BD. Future investigations of anti-inflammatory agents targeting cognitive function as a treatment outcome are merited. PMID- 26363614 TI - Confirmatory factor analysis of the Cornell scale for depression in dementia among patient with dementia of various degrees. AB - BACKGROUND: Depression in dementia is difficult to diagnose. The psychometric qualities of the Cornell scale for depression in dementia and whether depression varies depending on the dementia severity are still controversial. DESIGN: Cross sectional study of memory clinic and nursing-home patients. METHODS: A sample of 1682 patients (750 from memory clinics and 932 from nursing homes) with Clinical dementia rating scale score of one or higher was evaluated with the Cornell scale. The sample was randomly divided into two groups. Exploratory factor analysis was performed on one-half of the patients and confirmatory factor analysis on the other half. It was further analysed whether the scores of the sub scales differed across CDR score. RESULTS: A five-factor solution fitted the data best according to both the exploratory and confirmatory factor analysis: 'mood', 'physical', 'cyclic', 'retardation' and 'behaviour'. Further, it was found that the sum score of the Cornell scale differs significantly across dementia severity (p=0.018). The mood and the cyclic sub-scales scores did not vary across dementia severity, unlike the three remaining sub-scales scores. CONCLUSION: A five-factor solution of the Cornell scale best fitted the data according to both exploratory and confirmatory factor analysis. The mood and cyclic factors' scores did not vary across dementia severity, and this might suggest that they are the core symptoms of depression that are equally present regardless of dementia severity. The other factors scores were higher in severe dementia, which might suggest that these factors are related to the dementia. PMID- 26363615 TI - Men's use of positive strategies for preventing and managing depression: A qualitative investigation. AB - BACKGROUND: One in eight men experience depression and men account for 75% of suicides. Previous research has focused on men's reluctance to seek help and use of unhelpful coping strategies. METHOD: Thematic analysis was used on transcripts from 21 focus groups and 24 in-depth interviews focused on positive strategies men use to prevent and manage depression. RESULTS: In total, 168 men were recruited and the majority (63%) reported no current depression. Four major themes were identified, where men: (1) used a broad variety of positive strategies and made clear distinctions between prevention and management, (2) used strategies that were "typically masculine", as well as challenged expectations of manliness, (3) felt powerless in the face of suicide, and (4) had accumulated wisdom they felt was beneficial for others. Men specifically advised others to talk about problems. Prevention relied upon regular routines for "balance", while management relied upon "having a plan". LIMITATIONS: The majority of the men were aged over 55 years and highly educated. Younger men or those without tertiary education may favour different strategies. CONCLUSIONS: In contrast to using only unhelpful strategies, the men used a broad range of positive strategies and adapted their use depending on mood, symptom or problem severity. Use of positive strategies was sophisticated, nuanced, and often underlined by a guiding philosophy. Rather than simply reacting to problems, men actively engaged in preventing the development of depressed moods, and made conscious choices about when or how to take action. Clinical and public health implications are discussed. PMID- 26363616 TI - A preliminary investigation of a novel training to target cognitive biases towards negative social stimuli in Anorexia Nervosa. AB - BACKGROUND: Patients with Anorexia Nervosa (AN) experience high levels of social difficulties and anxiety. These problems might be underpinned by negatively biased processing of social stimuli. The aim of this study was to examine the feasibility of using a novel Cognitive Bias Modification (CBM) training to target information processing biases in patients with AN. METHODS: Twenty-eight patients with AN completed a baseline and end of intervention assessment of mood and social appraisals. The CBM training consisted of 5 sessions and included an attentional probe task to train attention towards positive social stimuli and an ambiguous scenarios task to train benign or neutral interpretations of ambiguous social scenarios. RESULTS: At baseline patients displayed an attention and interpretation bias towards negative social stimuli. At the end of intervention there was a medium sized increase in attention to positive faces and fewer negative interpretations of ambiguous social stimuli. There were also lower levels of anxiety and higher levels of self-compassion in response to a judgemental video clip. LIMITATIONS: The lack of a control group is the main limitation to this preliminary study as the changes obtained may have resulted from non-specific aspects of the inpatient treatment. CONCLUSIONS: A novel CBM training is associated with more positive processing of social information in AN. It would be of interest to test the hypothesis that reducing cognitive biases towards social stimuli impacts on wider features of an eating disorder. PMID- 26363617 TI - Interpretation of ambiguity: Differences between children and adolescents with and without an anxiety disorder. AB - BACKGROUND: Theory and treatment of anxiety disorders in young people are commonly based on the premise that interpretation biases found in anxious adults are also found in children and adolescents. Although there is some evidence that this may be the case, studies have not typically taken age into account, which is surprising given the normative changes in cognition that occur throughout childhood. The aim of the current study was to identify whether associations between anxiety disorder status and interpretation biases differed in children and adolescents. METHODS: The responses of children (7-10 years) and adolescents (13-16 years) with and without anxiety disorders (n=120) were compared on an ambiguous scenarios task. RESULTS: Children and adolescents with an anxiety disorder showed significantly higher levels of threat interpretation and avoidant strategies than non-anxious children and adolescents. However, age significantly moderated the effect of anxiety disorder status on interpretation of ambiguity, in that adolescents with anxiety disorders showed significantly higher levels of threat interpretation and associated negative emotion than non-anxious adolescents, but a similar relationship was not observed among children. CONCLUSIONS: The findings suggest that theoretical accounts of interpretation biases in anxiety disorders in children and adolescents should distinguish between different developmental periods. For both ages, treatment that targets behavioral avoidance appears warranted. However, while adolescents are likely to benefit from treatment that addresses interpretation biases, there may be limited benefit for children under the age of ten. PMID- 26363618 TI - Control-related frontal-striatal function is associated with past suicidal ideation and behavior in patients with recent-onset psychotic major mood disorders. AB - OBJECTIVE: Suicide is highly-prevalent in major mood disorders, yet it remains unclear how suicidal ideation and suicidal behavior relate to brain functions, especially those that support control processes. We evaluated how prefrontal cortex (PFC) activity during goal-representation (an important component of cognitive control) relates to past suicidal ideation and behavior in patients with psychotic major mood disorders. METHOD: 30 patients with recent-onset of either DSM-IV-TR-defined bipolar disorder type I (n=21) or major depressive disorder (n=9) with psychotic features, but neither in a major mood episode nor acutely psychotic at study, were evaluated for past suicidal ideation and behavior (Columbia Suicide Severity Rating Scale) and functional MRI during cognitive control task performance. Group-level regression models of brain activation accounted for current depression, psychosis and trait impulsivity. RESULTS: Intensity of past suicidal ideation was associated with higher control related activation in right-hemisphere regions including the ventrolateral PFC (VLPFC) and orbitofrontal cortex, rostral insula, and dorsal striatum. Among those with past suicidal ideation (n=16), past suicidal behavior (n=8) was associated with higher control-related activation in right-hemisphere regions including VLPFC, rostrolateral PFC, and frontal operculum/rostral insula; and relatively lower activity in midline parietal regions, including cuneus and precuneus. LIMITATIONS: The sample size of subjects with past suicidal behavior was modest, and all subjects were taking psychotropic medication. CONCLUSIONS: This study provides unique evidence that in early-course psychotic major mood disorders, suicidal ideation and behavior histories directly relate to PFC-based circuit function in support of cognitive control. PMID- 26363619 TI - Assessment of functional tag single nucleotide polymorphisms within the DRD2 gene as risk factors for post-traumatic stress disorder in the Han Chinese population. AB - BACKGROUND: Gene variations related to the dopaminergic pathway have been implicated in a number of neuropsychiatric disorders, including post-traumatic stress disorder (PTSD). Dopamine D2 receptor (DRD2) has been shown to significantly contribute to neuropsychiatric disorders and may specifically contribute to predisposition to PTSD. This study aimed to evaluate the association of polymorphisms within the entire DRD2 gene with PTSD in a case control study. MATERIALS AND METHODS: A total of 834 unrelated Han Chinese adults, including 497 healthy volunteers and 337 patients with PTSD, were used in this study. Fifteen tag single-nucleotide polymorphisms (tSNPs) were selected spanning the entire DRD2 gene through the construction of haplotype bins. Genotypes were gathered using an improved multiplex ligation detection reaction (iMLDR) technique. Allelic frequencies and clinical characteristics were compared in two independent Han Chinese populations. Moreover, the functionality of the rs2075652 and rs7131056 polymorphisms were assessed by measuring transcriptional enhancer activities. RESULTS: Fifteen tag SNPs were identified in the Han Chinese population and all were common SNPs. Among 15 tSNPs, two of them (rs2075652 and rs7131056) significantly associated with PTSD. PTSD individuals were more likely to carry the rs2075652A and rs7131056A allele compared to the controls (P<0.05). The haplotype GTGATCGCGCAGGCG, had a risk effect on PTSD occurrence (OR=1.75, 95% CI: 1.24-2.48, P=0.002). Additionally, the rs2075652 polymorphism contained intronic enhancer activities. CONCLUSIONS: The rs2075652 and rs7131056 polymorphisms, and the haplotype GTGATCGCGCAGGCG within the DRD2 gene, may be potential markers to predict susceptibility to PTSD. PMID- 26363620 TI - Addressing key issues in the consanguinity-related risk of autosomal recessive disorders in consanguineous communities: lessons from a qualitative study of British Pakistanis. AB - Currently, there is no consensus regarding services required to help families with consanguineous marriages manage their increased genetic reproductive risk. Genetic services for communities with a preference for consanguineous marriage in the UK remain patchy, often poor. Receiving two disparate explanations of the cause of recessive disorders (cousin marriage and recessive inheritance) leads to confusion among families. Further, the realisation that couples in non consanguineous relationships have affected children leads to mistrust of professional advice. British Pakistani families at-risk for recessive disorders lack an understanding of recessive disorders and their inheritance. Such an understanding is empowering and can be shared within the extended family to enable informed choice. In a three-site qualitative study of British Pakistanis, we explored family and health professional perspectives on recessively inherited conditions. Our findings suggest, firstly, that family networks hold strong potential for cascading genetic information, making the adoption of a family centred approach an efficient strategy for this community. However, this is dependent on provision of high-quality and timely information from health care providers. Secondly, families' experience was of ill-coordinated and time-starved services, with few having access to specialist provision from Regional Genetics Services; these perspectives were consistent with health professionals' views of services. Thirdly, we confirm previous findings that genetic information is difficult to communicate and comprehend, further complicated by the need to communicate the relationship between cousin marriage and recessive disorders. A communication tool we developed and piloted is described and offered as a useful resource for communicating complex genetic information. PMID- 26363621 TI - The histone variant H2A.Z is dynamically expressed in the developing mouse placenta and in differentiating trophoblast stem cells. AB - The histone variant H2A.Z is important in establishing new chromatin environments necessary for permitting changes in gene expression and thus differentiation in mouse embryonic stem (mES) cells. In this study we show that H2A.Z is highly expressed in the early mouse placenta, and is specifically limited to progenitor like trophoblast cells. Using in vitro models, we revealed distinct differences in H2A.Z abundance between undifferentiated, differentiating and differentiated mouse trophoblast stem (mTS) cells. Our work supports the hypothesis that in addition to roles in differentiating mES cells, H2A.Z is also involved in the differentiation of extra-embryonic tissues. PMID- 26363622 TI - Twenty years of National Reference and Consultant laboratories for infectious diseases in Germany. PMID- 26363623 TI - Death due to diabetic ketoacidosis: Induction by the consumption of synthetic cannabinoids? AB - We present a case study on a man who suffered from diabetic ketoacidosis, probably following consumption of synthetic cannabinoids. In blood from a femoral vein AB-CHMINACA, AB-FUBINACA, AM-2201, 5F-AMB, 5F-APINACA, EAM-2201, JWH-018, JWH-122, MAM-2201, STS135 and THJ 2201 could be detected by LC-MS/MS. Diagnosis of ketoacidosis as cause of death was carried out using biochemical measurements of glucose and lactate concentrations in vitreous humour (sum formula: 463 mg/dl) and cerebrospinal fluid (sum formula: 506 mg/dl), of acetone (163 mg/l in femoral venous blood) and of HbA1c (98 mmol/mol). Death due to hyperglycaemia could have been induced by skipping of insulin doses due to his intoxicated state or by the cannabinoids which were described to be able to produce hyperglycaemia themselves. PMID- 26363624 TI - Discrimination of ginseng cultivation regions using light stable isotope analysis. AB - Korean ginseng is considered to be a precious health food in Asia. Today, thieves frequently compromise ginseng farms by pervasive theft. Thus, studies regarding the characteristics of ginseng according to growth region are required in order to deter ginseng thieves and prevent theft. In this study, 6 regions were selected on the basis of Korea regional criteria (si, gun, gu), and two ginseng farms were randomly selected from each of the 6 regions. Then 4-6 samples of ginseng were acquired from each ginseng farm. The stable isotopic compositions of H, O, C, and N of the collected ginseng samples were analyzed. As a result, differences in the hydrogen isotope ratios could be used to distinguish regional differences, and differences in the nitrogen isotope ratios yielded characteristic information regarding the farms from which the samples were obtained. Thus, stable isotope values could be used to differentiate samples according to regional differences. Therefore, stable isotope analysis serves as a powerful tool to discriminate the regional origin of Korean ginseng samples from across Korea. PMID- 26363625 TI - Omics Approaches for the Engineering of Pathogen Resistant Plants. AB - The attack of different pathogens, such as bacteria, fungi and viruses has a negative impact on crop production. In counter such attacks, plants have developed different strategies involving the modification of gene expression, activation of several metabolic pathways and post-translational modification of proteins, which culminate into the accumulation of primary and secondary metabolites implicated in plant defense responses. The recent advancement in omics techniques allows the increase coverage of plants transcriptomes, proteomes and metabolomes during pathogen attack, and the modulation of the response after the infection. Omics techniques also allow us to learn more about the biological cycle of the pathogens in addition to the identification of novel virulence factors in pathogens and their host targets. Both approaches become important to decipher the mechanism underlying pathogen attacks and to develop strategies for improving disease-resistant plants. In this review, we summarize some of the contribution of genomics, transcriptomics, proteomics, metabolomics and metallomics in devising the strategies to obtain plants with increased resistance to pathogens. These approaches constitute important research tools in the development of new technologies for the protection against diseases and increase plant production. PMID- 26363626 TI - Relationships between preclinical course grades and standardized exam performance. AB - Success in residency matching is largely contingent upon standardized exam scores. Identifying predictors of standardized exam performance could promote primary intervention and lead to design insights for preclinical courses. We hypothesized that clinically relevant courses with an emphasis on higher-order cognitive understanding are most strongly associated with performance on United States Medical Licensing Examination Step exams and National Board of Medical Examiners clinical subject exams. Academic data from students between 2007 and 2012 were collected. Preclinical course scores and standardized exam scores were used for statistical modeling with multiple linear regression. Preclinical courses were categorized as having either a basic science or a clinical knowledge focus. Medical College Admissions Test scores were included as an additional predictive variable. The study sample comprised 795 graduating medical students. Median score on Step 1 was 234 (interquartile range 219-245.5), and 10.2 % (81/795) scored lower than one standard deviation below the national average (205). Pathology course score was the strongest predictor of performance on all clinical subject exams and Step exams, outperforming the Medical College Admissions Test in strength of association. Using Pathology score <75 as a screening metric for Step 1 score <205 results in sensitivity and specificity of 37 and 97 %, respectively, and a likelihood ratio of 11.9. Performance in Pathology, a clinically relevant course with case-based learning, is significantly related to subsequent performance on standardized exams. Multiple linear regression is useful for identifying courses that have potential as risk stratifiers. PMID- 26363627 TI - The Vertebral Fracture Cascade: Etiology and Clinical Implications. AB - A vertebral fracture is a marker of bone fragility and is associated with a downward spiral of recurrent fractures known as the vertebral fracture cascade. Etiology of this unfortunate cascade includes bone and muscle loss from immobility, changes in spinal mechanics causing increased loading on adjacent vertebrae, and the development of an increased thoracic kyphosis (hyperkyphosis [HK]). Degenerative disc disease, common in osteoporotic patients, can also cause HK. HK of any etiology has been associated with decreased thoracic extensor muscle strength, unstable gait, increased body sway, decreased physical and pulmonary functions, chronic pain, and increased spinal loads contributing to the vertebral fracture cascade. Preventing this downward spiral requires a multidisciplinary approach that includes early identification, consideration of pharmacologic treatment, early mobilization of the fracture patient, appropriate exercise, and back protection. Exercise should include weight-bearing and muscle strengthening activities, but caution is needed to avoid undue stress on the back. Physical therapy can be particularly helpful by teaching the patient how to safely perform daily activities and can assist the patient in establishing a safe exercise program that avoids flexion but promotes back extension and weight bearing activities. Hopefully, these measures will decrease pain, prevent falls, improve posture, prevent additional bone and muscle loss, and potentially abort the devastating downward spiral of the vertebral fracture cascade. PMID- 26363628 TI - Epidemiology of travel-associated infections in Oman 1999-2013: A retrospective analysis. AB - BACKGROUND: The number of travelers in Oman has increased significantly in the last 2 decades with an increase in the expatriate population workforce leading to the emergence of infections related to travel. This paper aims to highlight the burden of travel-related infections in Oman. METHOD: Our study is a descriptive record-based review and analysis of travel-associated diseases over a 14 year time period from 1999 to 2013. The data was sourced from the communicable disease surveillance system, and central public health laboratory results. RESULTS: From 1999 to 2013 there were a combined total of 7022 cases of cholera, chikungunya, dengue, filariasis, leptospirosis, meningococcal infection, poliomyelitis, measles, schistosomiasis, viral hepatitis (A), typhoid and para-typhoid reported to and subsequently investigated by the Department of Communicable Diseases. Among these cases, 558 (7.9%) were attributed to travel. Fifty percent of these patients were admitted to hospitals. CONCLUSION: Travel-associated infections account for about 8% of notifiable infections in Oman and have low mortality rate. However, some travel-associated infections are considered as a threat to polio eradication and measles elimination programs. Furthermore, some can cause outbreaks that can overwhelm the healthcare system. PMID- 26363630 TI - Acrimonious acronymania. PMID- 26363629 TI - Association between hyperuricemia and clinical adverse outcomes after percutaneous coronary intervention: A meta-analysis. PMID- 26363631 TI - Intra-carotid arterial administration of autologous peripheral blood-derived endothelial progenitor cells improves acute ischemic stroke neurological outcomes in rats. AB - OBJECTIVE: We tested the hypothesis that transfusion of autologous peripheral blood-derived endothelial progenitor cells (PBDEPC) via the internal carotid artery could reduce brain-infarct zone (BIZ) and neurological deficit in rats following acute ischemic stroke (IS) induced by 50-min left middle cerebral artery occlusion. DESIGN: Adult male Sprague-Dawley rats (n=60) were equally divided into group 1 [sham control (SC)], group 2 [SC-PBDEPC (5.7 * 10(6)/kg)], group 3 (IS), group 4 [IS-low-dose PBDEPC (1.7 * 10(6)/kg)], group 5 [IS-high dose PBDEPC (5.7*10(6)/kg)]. Groups 2 to 5 received G-CSF (35 MUg/kg subcutaneously) for 4 days before drawing blood for PBDEPC culture. MEASUREMENTS AND MAIN RESULTS: By day 90, BIZ determined by histopathology (area) and brain MRI (volume) were highest in group 3, lowest in groups 1 and 2, higher in group 4 than in group 5 (all p<0.0001), and not significantly different between groups 1 and 2. Sensorimotor functional results exhibited an opposite pattern of BIZ among groups 3 to 5 (p<0.005). Angiogenesis biomarkers (SDF-1alpha, CXCR4, VEGF, angiopoietin-1) significantly increased progressively from groups 1 and 2 to group 5 (all p<0.0001). Oxidative-stress (NOX-1, NOX-2, oxidized protein), apoptotic (cleaved caspase 3 and PARP, mitochondrial Bax), inflammatory (MMP-9, TNF-alpha, AQP-4, GFAP, iNOS), and brain-damaged (cytosolic cytochrome-C) biomarkers showed an identical pattern, whereas anti-inflammatory (Bcl-2), mitochondrial preservation (mitochondrial cytochrome-C, PGC-1alpha), and endothelial function (CD31+, vWF+, eNOS) biomarkers, and vessel density showed an opposite pattern of BIZ among these five groups (all p<0.001). CONCLUSION: Higher dose was superior to lower-dose EPC treatment for reducing BIZ and improving neurological functional outcome. PMID- 26363632 TI - Impella ventricular support in clinical practice: Collaborative viewpoint from a European expert user group. AB - Mechanical circulatory support represents an evolving field of clinical research and practice. Currently, several cardiac assist devices have been developed but, among different institutions and countries, a large variation in indications for use and device selection exists. The Impella platform is an easy to use percutaneous circulatory support device which is increasingly used worldwide. During 2014, we established a working group of European physicians who have collected considerable experience with the Impella device in recent years. By critically comparing the individual experiences and the operative protocols, this working group attempted to establish the best clinical practice with the technology. The present paper reviews the main theoretical principles of Impella and provides an up-to-date summary of the best practical aspects of device use which may help others gain the maximal advantage with Impella technology in a variety of clinical settings. PMID- 26363633 TI - Discovery of highly soluble antibodies prior to purification using affinity capture self-interaction nanoparticle spectroscopy. AB - Self-association of monoclonal antibodies (mAbs) at high concentrations can result in developability challenges such as poor solubility, aggregation, opalescence and high viscosity. There is a significant unmet need for methods that can evaluate self-association propensities of concentrated mAbs at the earliest stages in antibody discovery to avoid downstream issues. We have previously developed a method (affinity-capture self-interaction nanoparticle spectroscopy, AC-SINS) that is capable of detecting weak antibody self interactions using unusually dilute mAb solutions (tens of ug/ml). Here we optimize and implement this assay for characterization of unpurified and highly dilute mAbs directly in cell culture media. This assay was applied to screen 87 mAbs obtained via immunization. Our measurements reveal a wide range of self associative propensities for mAbs that bind to the same antigen and which differ mainly in their complementarity-determining regions. The least associative mAbs identified by AC-SINS were confirmed to be highly soluble when purified and concentrated by three to five orders of magnitude. This approach represents a key advance in screening mAb variants using unpurified antibody samples, and it holds significant potential to both improve initial candidate selection as well as to guide protein engineering efforts to improve the properties of specific mAb candidates. PMID- 26363634 TI - Exploration of the R code-based mathematical model for PMI estimation using profiling of RNA degradation in rat brain tissue at different temperatures. AB - Precise estimation of postmortem interval (PMI) is crucial in some criminal cases. This study aims to find some optimal markers for PMI estimation and build a mathematical model that could be used in various temperature conditions. Different mRNA and microRNA markers in rat brain samples were detected using real time fluorescent quantitative PCR at 12 time points within 144 h postmortem and at temperatures of 4, 15, 25, and 35 degrees C. Samples from 36 other rats were used to verify the animal mathematical model. Brain-specific mir-9 and mir-125b are effective endogenous control markers that are not affected by PMI up to 144 h postmortem under these temperatures, whereas the commonly used U6 is not a suitable endogenous control in this study. Among all the candidate markers, DeltaCt (beta-actin) has the best correlation coefficient with PMI and was used to build a new model using R software which can simultaneously manage both PMI and temperature parameters. This animal mathematical model is verified using samples from 36 other rats and shows increased accuracy for higher temperatures and longer PMI. In this study, beta-actin was found to be an optimal marker to estimate PMI and some other markers were found to be suitable to act as endogenous controls. Additionally, we have used R code software to build a model of PMI estimation that could be used in various temperature conditions. PMID- 26363635 TI - Takotsubo cardiomyopathy associated with rupture of the left ventricular apex: assessment of histopathological features of a fatal case and literature review. AB - Takotsubo cardiomyopathy, also known as "broken heart syndrome," is a cardiac entity characterized by transient left ventricular dysfunction without obstructive atherosclerotic coronary artery disease. An episode of emotional stress is believed to act as a trigger in the development of this syndrome, which typically occurs in female patients. We report a fatal case of a previously healthy 70-year-old woman who suffered an out-of-hospital cardiac arrest and cardiac rupture during emotional distress, due to Takotsubo cardiomyopathy. Ventricular rupture with Takotsubo cardiomyopathy is rare, but our case emphasizes the importance of dealing with this serious and potentially life threatening disease. Takotsubo cardiomyopathy should be considered as a differential diagnosis in cases of early-developing heart failure, and clinicians should subsequently use adequate diagnostic and therapeutic options. PMID- 26363636 TI - Combination therapy for carbapenem-resistant Enterobacteriaceae: increasing evidence, unanswered questions, potential solutions. AB - Carbapenem-resistant Enterobacteriaceae (CRE) are associated with a high mortality rate and are an increasing problem worldwide. In this mini-review, we consider the growing number of observational studies in favour of combination therapy but highlight the absence of randomised control trials. We discuss the importance of data on minimum inhibitory concentrations (MICs), both for surveillance and for individual patient management. We examine the issues surrounding the use of carbapenems, polymyxins and tigecycline in the treatment of CRE. When and how should we be using carbapenems? Which polymyxin is best? Is tigecycline much maligned? Further studies are urgently needed to validate drug combinations, doses and ratios to maximise efficacy whilst reducing drug exposure and adverse effects. PMID- 26363637 TI - Nasopharyngeal carriage and macrolide resistance in Indigenous children with bronchiectasis randomized to long-term azithromycin or placebo. AB - Although long-term azithromycin decreases exacerbation frequency in bronchiectasis, increased macrolide resistance is concerning. We investigated macrolide resistance determinants in a secondary analysis of a multicenter randomized controlled trial. Indigenous Australian children living in remote regions and urban New Zealand Maori and Pacific Islander children with bronchiectasis were randomized to weekly azithromycin (30 mg/kg) or placebo for up to 24 months and followed post-intervention for up to 12 months. Nurses administered and recorded medications given and collected nasopharyngeal swabs 3 6 monthly for culture and antimicrobial susceptibility testing. Nasopharyngeal carriage of Haemophilus influenzae and Moraxella catarrhalis was significantly lower in azithromycin compared to placebo groups, while macrolide-resistant Streptococcus pneumoniae and Staphylococcus aureus carriage was significantly higher. Australian children, compared to New Zealand children, had higher carriage overall, significantly higher carriage of macrolide-resistant bacteria at baseline (16/38 versus 2/40 children) and during the intervention (69/152 versus 22/239 swabs), and lower mean adherence to study medication (63 % versus 92 %). Adherence >=70 % (versus <70 %) in the Australian azithromycin group was associated with lower carriage of any pathogen [odds ratio (OR) 0.19, 95 % confidence interval (CI) 0.07-0.53] and fewer macrolide-resistant pathogens (OR 0.34, 95 % CI 0.14-0.81). Post-intervention (median 6 months), macrolide resistance in S. pneumoniae declined significantly in the azithromycin group, from 79 % (11/14) to 7 % (1/14) of positive swabs, but S. aureus strains remained 100 % macrolide resistant. Azithromycin treatment, the Australian remote setting, and adherence <70 % were significant independent determinants of macrolide resistance in children with bronchiectasis. Adherence to treatment may limit macrolide resistance by suppressing carriage. PMID- 26363639 TI - Is aerobic workload positively related to ambulatory blood pressure? A cross sectional field study among cleaners. AB - PURPOSE: Cardiovascular disease is prevalent among workers with high levels of occupational physical activity. The increased risk may be due to a high relative aerobic workload, possibly leading to increased blood pressure. However, studies investigating the relation between relative aerobic workload and ambulatory blood pressure (ABP) are lacking. The aim was to explore the relationship between objectively measured relative aerobic workload and ABP. METHODS: A total of 116 cleaners aged 18-65 years were included after informed consent was obtained. A portable device (Spacelabs 90217) was mounted for 24-h measurements of ABP, and an Actiheart was mounted for 24-h heart rate measurements to calculate relative aerobic workload as percentage of relative heart rate reserve. A repeated-measure multi-adjusted mixed model was applied for analysis. RESULTS: A fully adjusted mixed model of measurements throughout the day showed significant positive relations (p < 0.001): a 1% increase in mean relative aerobic workload was associated with an increase of 0.42 +/- 0.05 mmHg (95% CI 0.32-0.52 mmHg) in systolic ABP and 0.30 +/- 0.04 mmHg (95% CI 0.22-0.38 mmHg) in diastolic ABP. Correlations between relative aerobic workload and ABP were significant. CONCLUSIONS: Because workers may have an elevated relative aerobic workload for several hours each working day, this relationship may elucidate a mechanism behind the increased risk for cardiovascular disease among workers exposed to high levels of occupational physical activity. PMID- 26363638 TI - 3,5-Disubstituted Isoxazole Derivatives: Potential Inhibitors of Inflammation and Cancer. AB - The products of arachidonic acid metabolism by lipoxygenase (LOX) and cyclooxygenase (COX) significantly contribute to inflammation and carcinogenesis. Particularly, overproduction of leukotrienes and prostaglandins contribute to tumor growth by inducing formation of new blood vessels that sustain tumor cell viability and growth. Hence, search for novel anticancer drug via inhibition of LOX and COX enzymes constitutes an impressive strategy till date. In this context, a series of isoxazole derivatives were synthesized and screened for their anti-inflammatory activity via LOX and COX inhibition. Among these, 3-(3 methylthiophen-2-yl)-5-(3,4,5-trimethoxyphenyl)isoxazole (2b) showed significant inhibitory activity toward LOX and COX-2. Additionally, 2b showed a good inhibition of tumor growth, peritoneal angiogenesis, and ascite formation in Ehrlich ascites carcinoma (EAC) cell mouse model. Further, the in silico molecular studies also revealed that the compound 2b binds to the catalytic domain of LOX and COX-1 and COX-2 strongly with high atomic contact energy (ACE) score compared to standard drug. These initial pharmacological data support the fact that the compound 2b serves as the basis in developing anti-inflammatory and anticancer agents. PMID- 26363642 TI - Characterization of a spermidine hydroxycinnamoyltransferase in Malus domestica highlights the evolutionary conservation of trihydroxycinnamoyl spermidines in pollen coat of core Eudicotyledons. AB - Phenolamides, so called hydroxycinnamic acid amides, are specialized metabolites produced in higher plants, involved in development, reproduction and serve as defence compounds in biotic interactions. Among them, trihydroxycinnamoyl spermidine derivatives were initially found to be synthetized by a spermidine hydroxycinnamoyltransferase (AtSHT) in Arabidopsis thaliana and to accumulate in the pollen coat. This study reports the identification, in Malus domestica, of an acyltransferase able to complement the sht mutant of Arabidopsis. The quantitative RT-PCR expression profile of MdSHT reveals a specific expression in flowers coordinated with anther development and tapetum cell activities. Three phenolamides including N (1),N (5),N (10)-tricoumaroyl spermidine and N (1),N (5) dicoumaroyl-N (10)-caffeoyl spermidine identified by LC/MS, were shown to accumulate specifically in pollen grain coat of apple tree. Moreover, in vitro biochemical characterization confirmed MdSHT capacity to synthesize tri substituted spermidine derivatives with a substrate specificity restricted to p coumaroyl-CoA and caffeoyl-CoA as an acyl donor. Further investigations of the presence of tri-substituted hydroxycinnamoyl spermidine conjugates in higher plants were performed by targeted metabolic analyses in pollens coupled with bioinformatic analyses of putative SHT orthologues in a wide range of available plant genomes. This work highlights a probable early evolutionary appearance in the common ancestral core Eudicotyledons of a novel enzyme from the BAHD acyltransferase superfamily, dedicated to the synthesis of trihydroxycinnamoyl spermidines in pollen coat. This pathway was maintained in most species; however, recent evolutionary divergences have appeared among Eudicotyledons, such as an organ reallocation of SHT gene expression in Fabales and a loss of SHT in Malvales and Cucurbitales. PMID- 26363640 TI - Apolipoprotein A1, B levels, and their ratio and the risk of a first stroke: a meta-analysis and case-control study. AB - The associations of levels of apolipoprotein A1 (ApoA1) and apolipoprotein B and ApoB/A1 ratio and risk of a first stroke have not been reliably documented. We performed a meta-analysis to summarize the relationships and confirmed them in a case-control study. We identified relevant publications in PubMed and Embase databases up to June 1, 2015. A Dersimonian-Laird random effects model was used to compute summary relative risks (RRs) and 95 % confidence intervals (CIs). A case-control study was conducted in a southern Chinese population. We included 8 cohort and 4 case-control studies (222,774 subjects; 10,032 first stroke events) in the meta-analysis. Reduced ApoA1 level and increased ApoB level and ApoB/A1 ratio was associated with a first stroke in cohort studies (RR 0.86 [95 % CI 0.79 0.94], 1.66 [1.62-1.69], and 1.66 [1.63-1.70], respectively) and reduced ApoA1 level and increased ApoB/A1 ratio in case-control studies (0.68 [0.47-0.99] and 1.76 [1.50-2.06], respectively). When stratified by stroke type in cohort studies, the RR for ischemic stroke was 0.83 (0.76-0.90), 1.36 (1.32-1.40), and 1.38 (1.35-1.42) for the 3 factors, respectively. In our case-control study (1013 cases; 1029 controls), the OR for a first ischemic stroke was 0.83 (0.74-0.92), 1.33 (1.18-1.48) and 2.10 (1.76-2.51), respectively, with increased ApoA1 level associated with hemorrhagic stroke (1.37 [1.06-1.78]). Meta-analysis suggests that reduced ApoA1 level and increased ApoB level and ApoB/A1 ratio are risk factors for a first ischemic but not hemorrhagic stroke. Elevated ApoA1 level may be a risk factor for a first hemorrhagic stroke. PMID- 26363641 TI - Development of a novel method to evaluate sialylation of glycoproteins and analysis of gp96 sialylation in Hela, SW1990 and A549 cell lines. AB - BACKGROUND: Glycoproteins play a critical role in the cellular activities of eukaryotes. Sialic acid is typically the outermost monosaccharide of glycolipids and glycoproteins, and is necessary for normal development. RESULTS: A strategy based on avidin-biotin affinity was established to enrich sialylated glycoproteins from HeLa cervical carcinoma, SW1990 pancreatic adenocarcinoma, and A549 lung adenocarcinoma cells. Using HPLC-MS/MS, western blot, real-time PCR, and enzyme-linked immunosorbent assay, gp96 was identified in all three cell lines. No significant difference in the protein expression of gp96 was detected at the whole cell level, but the amount of biotinylated gp96 in SW1990 cells was 30-40% lower than that in A549 and HeLa cells, and the amount of sialylated gp96 in SW1990 cells was 30% lower than that in A549 and HeLa cells. Immunoblotting results showed that the expression of sialyltransferase proteins in the total cell lysates from HeLa and A549 cells were higher than that in SW1990 cells. CONCLUSIONS: We established a new method for investigating the expression and sialylation of glycoproteins using metabolic labeling, click chemistry, and avidin-biotin affinity. We successfully used this method to purify sialylated glycoproteins from cancer cell lines. Our results showed that the levels of gp96 sialylation varied across different cancer cell lines, and this may be because of differences in sialyltransferase expression. PMID- 26363643 TI - Emergency response readiness for primary school children. AB - Objective The aim of the present study was to determine whether a 1-day basic life support (BLS) training program can significantly increase emergency response readiness for primary school children. Methods One hundred and seven children aged 11-12 years completed a program led by surf lifesaving instructors. A 50 item quiz was administered 1 week before and 1 and 8 weeks after training. Results Significant improvements were gained in knowledge of cardiopulmonary resuscitation (CPR; P<0.001), the response sequence for emergency situations (DRSABCD action plan) and various emergency scenarios, including choking (P<0.001) and severe bleeding (P<0.001). Knowledge and understanding were retained at the 8-week follow-up. Students reported increased confidence in assisting others after training, consistent with previous studies. Conclusions A 1-day training program can significantly increase BLS knowledge and confidence to provide assistance in an emergency situation. Findings reinforce the value of school-based training that provides a general foundation for emergency response readiness. What is known about this topic? The importance and value of teaching BLS to school children is well established in the US, UK and Europe. However, in the past 20 years there has been little or no published Australian evaluation research in this area, despite thousands of training programs running each year around the country for children in first aid, CPR and water safety. What does this paper add? This paper confirms that Australian primary school children can benefit significantly from short, targeted BLS training programs that provide the basic skills and confidence for them to respond in an emergency situation. What are the implications for practitioners? The paper provides a training and evaluation framework that can be used by health educators for age-appropriate BLS programs. The study shows that making training real-world and relevant, especially having hands-on CPR practice with manikins, can address common barriers to performing first aid and CPR reported by young people. PMID- 26363644 TI - Staphylococcus haemolyticus - an emerging threat in the twilight of the antibiotics age. AB - Staphylococcus haemolyticus is one of the most frequent aetiological factors of staphylococcal infections. This species seems to lack the important virulence attributes described in other staphylococci. However, studies have shown that the presence of various enzymes, cytolysins and surface substances affects the virulence of S. haemolyticus. Nevertheless, none of them has been identified as crucial and determinative. Despite this, S. haemolyticus is, after Staphylococcus epidermidis, the second most frequently isolated coagulase-negative staphylococcus from clinical cases, notably from blood infections, including sepsis. This raises the question of what is the reason for the increasing clinical significance of S. haemolyticus? The most important factor might be the ability to acquire multiresistance against available antimicrobial agents, even glycopeptides. The unusual genome plasticity of S. haemolyticus strains manifested by a large number of insertion sequences and identified SNPs might contribute to its acquisition of antibiotic resistance. Interspecies transfer of SCCmec cassettes suggests that S. haemolyticus might also be the reservoir of resistance genes for other staphylococci, including Staphylococcus aureus. Taking into consideration the great adaptability and the ability to survive in the hospital environment, especially on medical devices, S. haemolyticus becomes a crucial factor in nosocomial infections caused by multiresistant staphylococci. PMID- 26363645 TI - Description of Acinetobacter populi sp. nov. isolated from symptomatic bark of Populus x euramericana canker. AB - Five Gram-negative, non-motile, rod-shaped bacterial strains were isolated from cankers of Populus x euramericana collected from different locations in Puyang city, Henan Province, China. The five strains were characterized by nutritional and physiological testing and DNA sequence analysis. Haemolysis was not observed on agar media supplemented with sheep erythrocytes. The strains could be distinguished from members of most species of the genus Acinetobacter by their inability to assimilate L-arginine and benzoate. The five strains formed a single branch in phylogenetic trees based on 16S rRNA, gyrB and rpoB individual gene sequence analysis,indicating that they all belonged to a single taxon within the genus Acinetobacter. DNA-DNA hybridization results indicated that the five isolates represented to a single species that was separate from Acinetobacter puyangensis. On the basis of the phenotypic, genotypic and phylogenetic characteristics, the five strains are considered to represent a novel species of the genus Acinetobacter, for which the name Acinetobacter populi sp. nov. is proposed. The typestrain of A. populi sp. nov. is PBJ7T (CFCC 11170T=KCTC 42272T). PMID- 26363646 TI - Treadmill training for patients with Parkinson's disease. AB - BACKGROUND: Treadmill training is used in rehabilitation and is described as improving gait parameters of patients with Parkinson's disease. OBJECTIVES: To assess the effectiveness of treadmill training in improving the gait of patients with Parkinson's disease and the acceptability and safety of this type of therapy. SEARCH METHODS: We searched the Cochrane Movement Disorders Group Specialised Register (see Review Group details for more information) (last searched September 2014), Cochrane Central Register of Controlled Trials (The Cochrane Library 2014, Issue 10), MEDLINE (1950 to September 2014), and EMBASE (1980 to September 2014). We also handsearched relevant conference proceedings, searched trials and research registers, and checked reference lists (last searched September 2014). We contacted trialists, experts and researchers in the field and manufacturers of commercial devices. SELECTION CRITERIA: We included randomised controlled trials comparing treadmill training with no treadmill training in patients with Parkinson's disease. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion, assessed trial quality and extracted data. We contacted the trialists for additional information. We analysed the results as mean differences (MDs) for continuous variables and relative risk differences (RD) for dichotomous variables. MAIN RESULTS: We included 18 trials (633 participants) in this update of this review. Treadmill training improved gait speed (MD = 0.09 m/s; 95% confidence interval (CI) 0.03 to 0.14; P = 0.001; I(2) = 24%; moderate quality of evidence), stride length (MD = 0.05 metres; 95% CI 0.01 to 0.09; P = 0.01; I(2) = 0%; low quality of evidence), but walking distance (MD = 48.9 metres; 95% CI -1.32 to 99.14; P = 0.06; I(2) = 91%; very low quality of evidence) and cadence did not improve (MD = 2.16 steps/minute; 95% CI -0.13 to 4.46; P = 0.07; I(2) = 28%; low quality of evidence) at the end of study. Treadmill training did not increase the risk of patients dropping out from intervention (RD = -0.02; 95% CI -0.06 to 0.02; P = 0.32; I(2) = 13%; moderate quality of evidence). Adverse events were not reported in included studies. AUTHORS' CONCLUSIONS: This update of our systematic review provides evidence from eighteen trials with moderate to low risk of bias that the use of treadmill training in patients with PD may improve clinically relevant gait parameters such as gait speed and stride length (moderate and low quality of evidence, respectively). This apparent benefit for patients is, however, not supported by all secondary variables (e.g. cadence and walking distance). Comparing physiotherapy and treadmill training against other alternatives in the treatment of gait hypokinesia such as physiotherapy without treadmill training this type of therapy seems to be more beneficial in practice without increased risk. The gain seems small to moderate clinically relevant. However, the results must be interpreted with caution because it is not known how long these improvements may last and some studies used no intervention in the control group and underlie some risk of bias. Additionally the results were heterogenous and we found variations between the trials in patient characteristics, the duration and amount of training, and types of treadmill training applied. PMID- 26363649 TI - Multidisciplinary management of locally advanced pancreatic ductal adenocarcinoma. PMID- 26363650 TI - A Survey of Cardiothoracic Surgical Training in the United Kingdom: Realities of a 6-Year Integrated Training Program. AB - BACKGROUND: In recent years, cardiothoracic (CT) surgical training has faced several challenges, including a reduction in working hours and trainees favoring shorter training programs. We carried out a national survey in the United Kingdom (UK) to assess the CT 6-year training program. METHODS: All CT trainees in the UK (n = 121) were sent an online survey. This was combined with a debate at the Society for CT Surgery of Great Britain and Ireland. RESULTS: Ninety-one (75.2%) of all trainees responded. Despite 56 (68.1%) being rostered for more than a 48 hour week, 31 (34.1%) of all trainees work an extra 10 hours. The majority (56, 61.5%) thought that on-calls and night duty are useful. Just over half of the trainees (47, 51.6%) spend at least 2 full days in the operating room, but 79 (86.8%) thought that this is too little and would spend voluntary time operating. Simulation of operations is thought to be useful; however, few thought that this should take more precedence in their training program. The majority of trainees thought that the current assessment of surgical training is suboptimal and does not examine surgical skill. Similarly, the majority thought that a defined number of operations is required before qualification. CONCLUSIONS: Trainees remain committed to their profession and are willing to dedicate more time perfecting their art. They believe that despite wanting extra operating experience, they will be ready for independent practice at the completion of their training. It rests with training bodies to find alternative assessments for surgical ability and to define experience at the exit point of training. PMID- 26363651 TI - The Effectiveness of Postoperative Radiotherapy in Patients With Completely Resected Thymoma: A Meta-Analysis. AB - BACKGROUND: This meta-analysis aimed to provide a pooled analysis of clinical studies correlating postoperative radiotherapy (PORT) with survival in patients with completely resected thymoma. METHODS: According to the recommendations of the Cochrane Collaboration, we established a rigorous study protocol. An electronic search was conducted using online databases. Hazard ratios (HRs) and 95% confidence intervals (CIs) were used in this meta-analysis and were calculated from published survival data. A meta-analysis was conducted to assess the impact of PORT in completely resected thymoma on overall survival (OS), disease-free survival (DFS). and disease-specific survival (DSS). We also performed a subgroup analysis for OS of patients with stage II and stage III thymoma. RESULTS: Fourteen studies, which included 3,823 patients (2,096 patients who received PORT and 1,727 patients who did not receive PORT), met the selection criteria. From the available data, the thymoma patients with PORT who did not undergo resection did not have significantly improved OS (HR 0.99; 95% CI 0.87 to 1.13; p = 0.87), DFS (HR 1.21; 95% CI 0.97 to 1.51; p = 0.09), or DSS (HR 0.66; 95% CI 0.39 to 1.13; p = 0.13) compared with the patients who did not undergo PORT. However, our subgroup analysis showed a significant difference in OS in patients with stage II thymoma (HR 0.57; 95% CI 0.41 to 0.80; p = 0.001) and patients with stage III thymoma (HR 0.73; 95% CI 0.59 to 0.90; p = 0.004). CONCLUSION: Our results showed that for completely resected thymoma, PORT had no advantage in the overall group of patients but increased OS in the patients with stage II and III thymoma after a complete resection. On the basis of this study, PORT is beneficial in patients with stage II and III patients after a complete resection. PMID- 26363652 TI - Venous Thromboembolic Complications of Lung Transplantation: A Contemporary Single-Institution Review. AB - BACKGROUND: The incidence and consequences of deep venous thrombosis (DVT) and pulmonary embolism (PE) have not been described recently in lung transplant recipients. We sought to characterize DVT and PE in a contemporary series of lung transplant recipients and describe their association with clinical outcomes. METHODS: The records of all lung transplant recipients from July 1, 2008, to June 30, 2013, were reviewed and analyzed. DVT was diagnosed by venous duplex ultrasonography. PE was diagnosed by computed tomography angiography, nuclear ventilation/perfusion scanning, or pulmonary angiography. RESULTS: The study comprised 117 patients who underwent 123 transplants. The median age was 63 years (range, 17 to 77 years). Forty-five patients (39%) had evidence of lower extremity DVT, 53 (45%) had no evidence of lower extremity DVT, and 19 (16%) were not tested. Fifty-three (45%) had evidence of upper extremity DVT, 30 (26%) had no evidence of upper extremity DVT, and 34 (29%) were not tested. Eighteen (15%) had evidence of PE, 82 (70%) had no evidence of PE, and 17 (15%) were not tested. A multivariable, stepwise Cox proportional hazards model revealed that the presence of lower extremity DVT (hazard ratio, 2.43; 95% confidence interval, 1.29 to 4.64), use of cardiopulmonary bypass (hazard ratio, 2.21; 95% confidence interval, 1.04 to 4.68), and unilateral lung transplantation (hazard ratio, 2.13; 95% confidence interval, 1.07 to 4.25) were associated with diminished survival. CONCLUSIONS: The incidence of DVT and PE in lung transplant recipients is high. Posttransplant surveillance and treatment based on findings are warranted. PMID- 26363653 TI - Hydrodynamic Performance of the Medtronic CoreValve and the Edwards SAPIEN XT Transcatheter Heart Valve in Surgical Bioprostheses: An In Vitro Valve-in-Valve Model. AB - BACKGROUND: Valve-in-valve transcatheter aortic valve replacement (TAVR) is becoming a valuable option with promising clinical results in failed bioprosthetic heart valves. Sizing recommendations are based on size compatibility rather than on broad clinical data, in vitro measurements, or biomechanical evidence. The hemodynamic performance of transcatheter heart valves within degenerated surgical heart valves is unknown. METHODS: We evaluated the in vitro hydrodynamic performance of two commercially available transcatheter heart valves (Medtronic CoreValve [Medtronic, Minneapolis, MN] and Edwards SAPIEN XT [Edwards Lifesciences, Irvine, CA]) in two different bioprosthetic aortic valves (Edwards Perimount [Edwards Lifesciences] and St. Jude Trifecta [St. Jude Medical, St. Paul, MN]). RESULTS: Within the Edwards Perimount (23 mm) prosthesis, pressure gradients were higher for the SAPIEN XT compared with the CoreValve (11.2 +/- 0.1 mm Hg versus 10.1 +/- 0.1 mm Hg, p < 0.01), whereas effective orifice area (1.99 +/- 0.01 cm(2) versus 1.80 +/- 0.01 cm(2), p < 0.01) and total paravalvular leakage (9.0% +/- 1.0% versus 5.4% +/- 1.3%, p < 0.01) were increased when using the CoreValve. Similarly, measurements in the St. Jude Trifecta revealed higher transvalvular pressure gradients (13.0 +/- 0.2 mm Hg versus 10.9 +/- 0.3 mm Hg, p < 0.01) and lower effective orifice area for the SAPIEN XT compared with the CoreValve. However, total relative regurgitation was higher with SAPIEN XT as compared with the CoreValve in St. Jude Trifecta prostheses (11.2% +/- 1.4% versus 8.3% +/- 0.9%, p < 0.01). CONCLUSIONS: Both transcatheter heart valve prostheses performed well in the described valve-in valve settings. Hydrodynamic results were in line with the International Organization for Standardization standards for all configurations. The observed differences indicate a necessity for preclinical valve-in-valve tests in addition to clinical long-term data about longevity. PMID- 26363654 TI - Antegrade or Retrograde Cerebral Perfusion in Ascending Aorta and Hemiarch Surgery? A Propensity-Matched Analysis. AB - BACKGROUND: Over the years, numerous options have been proposed for surgical management of ascending aorta and aortic arch pathology in an attempt to minimize postoperative morbidity and probability of death. We present a propensity score matching analysis of 259 patients from a single unit who were operated on under deep hypothermic arrest with retrograde cerebral perfusion (DHCA/RCP) or moderate hypothermic circulatory arrest with selective antegrade cerebral perfusion (via common carotid artery) (MHCA/ACP). METHODS: Between 2006 and 2014 a total of 259 consecutive patients underwent ascending aorta and hemiarch correction under HCA. DHCA/RCP and MHCA/ACP were performed on 207 and 52 patients, respectively. Baseline patient characteristics accounted for in the propensity matching were age, sex, acute aortic dissection, emergency operation, re-operation, preoperative hemodynamic instability, preoperative kidney injury, and CA time. After propensity scoring 40 pairs (80 patients) were successfully matched (p = 0.732). Outcomes were defined as the incidence of postoperative neurologic complications, 30-day mortality, and all-cause midterm mortality. RESULTS: Surgical procedure that involved the MHCA/ACP technique was associated with 76.5% decreased risk (risk ratio, 0.235; 95% CI, 0.079 to 0.699) of postoperative neurologic complications (p = 0.009). In addition to MHCA/ACP in surgical procedure for acute aortic dissection a relevant trend was established for 30-day mortality (risk ratio, 0.333; 95% CI, 0.09 to 1.23). For midterm all-cause mortality, MHCA/ACP modestly decreased the number of deaths (p = 0.0456) in comparison with the DHCA/RCP technique. CONCLUSIONS: MHCA/ACP in aortic arch surgical procedure is associated with a decreased risk of all types of neurologic complications and a trend toward decreased 30-day and midterm mortality in comparison with DHCA/RCP. PMID- 26363655 TI - [Soins Psychiatrie, a reference for 35 years]. PMID- 26363656 TI - [Relevance of psychosocial rehabilitation in psychiatry]. PMID- 26363657 TI - [Psychosocial rehabilitation in France]. AB - For a long time in France, readaptation and reinsertion have been considered separately. While readaptation focuses on the way the patient "adapts again", reintegration looks at the place of the readaptation, the society or the group. Today, psychosocial rehabilitation encompasses both of these notions by taking into account the medical and social aspects. PMID- 26363658 TI - [Psychoeducation and cognitive remediation, which place in rehabilitation?]. AB - Rehabilitation techniques aim to reduce the functional impact of severe psychological disorders. The recent development of techniques aimed at the manifestations of the pathology, such as psychoeducation and cognitive remediation, raise questions about how they differ from standard therapies. Beyond their functional purpose, the consideration of the individual's current or future action potential, seems to constitute one of the key aspects. PMID- 26363659 TI - [Recovery]. AB - The historical fatalism of the impossibility of recovering from psychosis eased from the 1970s with the shaping of the idea of a possible recovery. Recovery is today the objective for the patient and caregivers. The key to achieving this lies in the encounter with Others. A collective approach, on the level of the institution, must be established. The aim is to create opportunities for the patient to express their doubts and feelings. PMID- 26363660 TI - [Nursing support in a housing association apartment]. AB - A transferable lease project jointly run by the municipal authorities, the departmental council, the local mental health council and the hospital, has been set up for the benefit of patients in the process of reintegration. In this context, the work of the nurse is based around the individual support of the patient, integration within networks and the establishment of the project within the community. PMID- 26363661 TI - [The benefit of self-assessment in rehabilitation]. AB - The clinical stabilisation of the patient is a phase which is favourable for carrying out self-assessment to help them determine their resources. Adapted assessment scales are useful tools. On the basis of these, an initial care project is put in place which takes shape as and when the assessments are carried out. Ensuring the patient follows a therapeutic education programme aims particularly at improving their knowledge of their health. PMID- 26363662 TI - [A warrior named Gaspard]. AB - "Gaspard is a warrior" is a metaphor highlighting the long battle undertaken by mental health patients to recover from their condition. At each stage, Gaspard, a fictional character embodying many of the patients seen by professionals, is given several therapeutic tools to help him carry out his fight. In the background, nurses, thanks to their key role and position, are important allies as they support the person with mental health problems on their path towards rehabilitation. This article reflects on the clinical approach. PMID- 26363663 TI - [Using money as a therapeutic tool in a therapeutic day centre]. AB - Can money be used as a tool in the resocialisation of patients? Other than the clinical and institutional issues which its use within a therapeutic day centre raises, it can nevertheless help the caregiver bring projects to fruition and the patients to become engaged in them. PMID- 26363664 TI - [4/5 Melanie Klein]. PMID- 26363665 TI - Sickness: From the focus on cytokines, prostaglandins, and complement factors to the perspectives of neurons. AB - Systemic inflammation leads to a variety of physiological (e.g. fever) and behavioral (e.g. anorexia, immobility, social withdrawal, depressed mood, disturbed sleep) responses that are collectively known as sickness. While these phenomena have been studied for the past few decades, the neurobiological mechanisms by which sickness occurs remain unclear. In this review, we first revisit how the body senses and responds to infections and injuries by eliciting systemic inflammation. Next, we focus on how peripheral inflammatory molecules such as cytokines, prostaglandins, and activated complement factors communicate with the brain to trigger neuroinflammation and sickness. Since depression also involves inflammation, we further elaborate on the interrelationship between sickness and depression. Finally, we discuss how immune activation can modulate neurons in the brain, and suggest future perspectives to help unravel how changes in neuronal functions relate to sickness responses. PMID- 26363666 TI - Neurological changes in brain structure and functions among individuals with a history of childhood sexual abuse: A review. AB - OBJECTIVE: Review literature focused on neurological associations in brain structure among individuals with a history of childhood sexual abuse (CSA). METHODOLOGY: A review of literature examining physiological irregularities in brain structures of individuals with a history of CSA was conducted. RESULTS: Results revealed that a history of CSA was associated with irregularities in the cortical and subcortical regions of the brain. These irregularities have been recognized to contribute to various cognitive, behavioral, and psychological health outcomes later in life. Age of CSA onset was associated with differential neurological brain structures. CONCLUSION: Mental and behavioral health problems such as anxiety, depression, substance abuse, dissociative disorders, and sexual dysfunction are associated with CSA and may persist into adulthood. Research depicting the associations of CSA on neurological outcomes emphasizes the need to examine the biological and subsequent psychological outcomes associated with CSA. Early intervention is imperative for CSA survivors. PMID- 26363668 TI - Midwives' and obstetricians' perceptions of risk and its impact on clinical practice and decision-making in labour: An integrative review. AB - BACKGROUND: Risk and risk assessment are increasingly affecting how maternity services are governed with rates of intervention continuing to rise in obstetric led services for low-risk women. AIM: This review synthesises original research that examines how perceptions of risk impact on midwives' and obstetricians' facilitation of care for low-risk women in labour. METHODS: A five stage process for conducting integrative reviews was employed. A robust search strategy incorporated electronic searches in The Cochrane Database of Systematic Reviews, EBSCO, EMBASE and Scopus from 2009 to 2014. The initial search resulted in the retrieval of 2429 articles which were reduced to 14 through a systematic process. FINDINGS: The results of this review revealed an over-arching theme of an assumption of abnormality in the birthing process leading to unnecessary intervention and surveillance. Three sub-themes are presented under this central theme - (1) external influences on risk perception that include practice guidelines and professional responsibility; (2) influence of personal fears and values on risk perception focusing on differing attitudes to physiological birth; (3) impact of professionals' perceptions of risk on women's decision-making in labour. CONCLUSION: Practice is influenced by an assumption of birth as abnormal and is compounded by issues such as institutional risk management, lack of midwifery responsibility, fear of involvement in adverse outcomes and personal values regarding physiological birth. These findings suggest that a shift in focus away from risk and towards health and wellbeing in the planning of maternity care may go some way towards providing a solution to the increasing intervention rates for low-risk women. PMID- 26363669 TI - The 'temporal effect' in hominids: Reinvestigating the nature of support for a chimp-human clade in bone morphology. AB - In 2004, an analysis by Lockwood and colleagues of hard-tissue morphology, using geometric morphometrics on the temporal bone, succeeded in recovering the correct phylogeny of living hominids without resorting to potentially problematic methods for transforming continuous shape variables into meristic characters. That work has increased hope that by using modern analytical methods and phylogenetically informative anatomical data we might one day be able to accurately infer the relationships of hominins, including the closest extinct relatives of modern humans. In the present study, using 3D virtually generated models of the hominid temporal bone and a larger suite of geometric morphometric and comparative techniques, we have re-examined the evidence for a Pan-Homo clade. Despite differences in samples, as well as the type of raw data, the effect of measurement error (and especially landmark digitization by a different operator), but also a broader perspective brought in by our diverse set of approaches, our reanalysis largely supports Lockwood and colleagues' original results. However, by focusing not only mainly on shape (as in the original 2004 analysis) but also on size and 'size-corrected' (non-allometric) shape, we demonstrate that the strong phylogenetic signal in the temporal bone is largely related to similarities in size. Thus, with this study, we are not suggesting the use of a single 'character', such as size, for phylogenetic inference, but we do challenge the common view that shape, with its highly complex and multivariate nature, is necessarily more phylogenetically informative than size and that actually size and size-related shape variation (i.e., allometry) confound phylogenetic inference based on morphology. This perspective may in fact be less generalizable than often believed. Thus, while we confirm the original findings by Lockwood et al., we provide a deep reinterpretation of their nature and potential implications for hominid phylogenetics and we show how crucial it is not to overlook size in geometric morphometric analyses. PMID- 26363670 TI - Is there any association between parental education and child mortality? A study in a rural area of Bangladesh. AB - OBJECTIVES: To assess the association between parental education and under-five mortality, using the Integrated Management of Childhood Illness (IMCI) data from rural Bangladesh. It also investigated whether the association of parental education with under-five mortality had changed over time. STUDY DESIGN: This study was nested in the IMCI cluster randomized controlled trial. METHODS: Participants considered for the analysis were all children aged under five years from the baseline (1995-2000) and the final (2002-2007) IMCI household survey. The analysis sample included 39,875 and 38,544 live births from the baseline and the final survey respectively. The outcome variable was under-five mortality and the exposure variables were mother's and father's education. Data were analysed with logistic regression. RESULTS: In 2002-2007, the odds of the under-five mortality were 38% lower for the children with mother having secondary education, compared to the children with uneducated mother. For similar educational differences for fathers, at the same time period, the odds of the under-five mortality were 16% lower. The association of mother's education with under-five mortality was significantly stronger in 2002-2007 compared to 1995-2000. CONCLUSIONS: Mother's education appears to have a strong and significant association with under-five mortality, compared to father's education. The association of mother's education with under-five mortality appears to have increased over time. Our findings indicate that investing on girls' education is a good strategy to combat infant mortality in developing countries. PMID- 26363667 TI - Dorsal raphe nucleus projecting retinal ganglion cells: Why Y cells? AB - Retinal ganglion Y (alpha) cells are found in retinas ranging from frogs to mice to primates. The highly conserved nature of the large, fast conducting retinal Y cell is a testament to its fundamental task, although precisely what this task is remained ill-defined. The recent discovery that Y-alpha retinal ganglion cells send axon collaterals to the serotonergic dorsal raphe nucleus (DRN) in addition to the lateral geniculate nucleus (LGN), medial interlaminar nucleus (MIN), pretectum and the superior colliculus (SC) has offered new insights into the important survival tasks performed by these cells with highly branched axons. We propose that in addition to its role in visual perception, the Y-alpha retinal ganglion cell provides concurrent signals via axon collaterals to the DRN, the major source of serotonergic afferents to the forebrain, to dramatically inhibit 5-HT activity during orientation or alerting/escape responses, which dis facilitates ongoing tonic motor activity while dis-inhibiting sensory information processing throughout the visual system. The new data provide a fresh view of these evolutionarily old retinal ganglion cells. PMID- 26363671 TI - [Smoking cessation in older smokers. A retrospective study in 181 older smokers managed in a smoking cessation clinic]. AB - INTRODUCTION: Smoking is a factor associated with premature death, including in older people. Stopping smoking reduces related mortality even after the age of 60. The aim of this study, conducted in a smoking cessation clinic, was to describe the characteristics of these older smokers and their quit attempts. METHOD: A retrospective study was performed from the patient files of a smoking cessation clinic between 1999/01/01 and 2009/12/31; "older" smokers (>=60 years; n=181) were compared to "young" smokers (<60 years; n=1425). RESULTS: Compared to young smokers, older smokers had a higher frequency of cardio-pulmonary diseases (82.3 % vs. 46.7 %; P<0.0001) and current depressions (45.3% vs. 35.7%; P=0.012); their abstinence rate at 12 months was higher (44.2% vs. 32.9%; P=0.0025). An age over 60 years was associated with a higher success rate (OR=1.83; CI 95%: 1.29 2.59). CONCLUSION: Cessation smoking attempts are as likely to be successful in older smokers as in younger smokers. Physicians should advise and assist older smokers to quit and if necessary refer them to smoking cessation clinics. Smoking cessation guidelines therefore will apply without reserve in seniors. PMID- 26363672 TI - Do We Need a Novel Nephrometry Scoring System in Partial Nephrectomy? PMID- 26363673 TI - Impact of Parkinson's disease and levodopa on resting state functional connectivity related to speech prosody control. AB - BACKGROUND: Impaired speech prosody is common in Parkinson's disease (PD). We assessed the impact of PD and levodopa on MRI resting-state functional connectivity (rs-FC) underlying speech prosody control. METHODS: We studied 19 PD patients in the OFF and ON dopaminergic conditions and 15 age-matched healthy controls using functional MRI and seed partial least squares correlation (PLSC) analysis. In the PD group, we also correlated levodopa-induced rs-FC changes with the results of acoustic analysis. RESULTS: The PLCS analysis revealed a significant impact of PD but not of medication on the rs-FC strength of spatial correlation maps seeded by the anterior cingulate (p = 0.006), the right orofacial primary sensorimotor cortex (OF_SM1; p = 0.025) and the right caudate head (CN; p = 0.047). In the PD group, levodopa-induced changes in the CN and OF_SM1 connectivity strengths were related to changes in speech prosody. CONCLUSIONS: We demonstrated an impact of PD but not of levodopa on rs-FC within the brain networks related to speech prosody control. When only the PD patients were taken into account, the association between treatment-induced changes in speech prosody and changes in rs-FC within the associative striato-prefrontal and motor speech networks was found. PMID- 26363674 TI - What's eating the internet? Content and perceived harm of pro-eating disorder websites. AB - The internet is a popular tool for information dissemination and community building, serving many purposes from social networking to support seeking. However, there may be a downside to using some online support communities. For individuals with eating disorders (EDs), it is possible that certain online communities may reinforce the negative social aspects that encourage these disorders, rather than positive aspects that would facilitate treatment and recovery. Previous research identified several linguistic themes present on pro eating disorder websites in an attempt to better understand the web-based conversation in the pro-eating disorder movement. We hypothesized that differences in theme presentation may predict changes in perceived harm. The present study sought to understand the perceived harm, and presentation patterns of pro-eating disorder (Pro-ED) website content. We replicated and extended previous research by having laypersons code these websites' content using previously identified linguistic themes and rate perceived harm. Our data replicate and extend the previous research by finding the same associations between co-occurring themes, and investigating associated perceived harm. We found that themes of Sacrifice, Control, Deceit, and Solidarity were associated with the highest perceived harm scores. In addition, we suggest an initial conceptualization of the "Eating Disorder Lifestyle", and its associations with the themes of Isolation, Success, and Solidarity. This research may provide clinicians with information to better understand the potential influence these sites have on eating disorders. PMID- 26363675 TI - Patients with back pain value the process, as well as outcomes, of care. AB - of May S (2001): An explorative, qualitative study into patients' satisfaction with physiotherapy. PMID- 26363676 TI - Evaluating geodesic active contours in microcalcifications segmentation on mammograms. AB - Breast cancer is the most commonly occurring type of cancer among women, and it is the major cause of female cancer-related deaths worldwide. Its incidence is increasing in developed as well as developing countries. Efficient strategies to reduce the high death rates due to breast cancer include early detection and tumor removal in the initial stages of the disease. Clinical and mammographic examinations are considered the best methods for detecting the early signs of breast cancer; however, these techniques are highly dependent on breast characteristics, equipment quality, and physician experience. Computer-aided diagnosis (CADx) systems have been developed to improve the accuracy of mammographic diagnosis; usually such systems may involve three steps: (i) segmentation; (ii) parameter extraction and selection of the segmented lesions and (iii) lesions classification. Literature considers the first step as the most important of them, as it has a direct impact on the lesions characteristics that will be used in the further steps. In this study, the original contribution is a microcalcification segmentation method based on the geodesic active contours (GAC) technique associated with anisotropic texture filtering as well as the radiologists' knowledge. Radiologists actively participate on the final step of the method, selecting the final segmentation that allows elaborating an adequate diagnosis hypothesis with the segmented microcalcifications presented in a region of interest (ROI). The proposed method was assessed by employing 1000 ROIs extracted from images of the Digital Database for Screening Mammography (DDSM). For the selected ROIs, the rate of adequately segmented microcalcifications to establish a diagnosis hypothesis was at least 86.9%, according to the radiologists. The quantitative test, based on the area overlap measure (AOM), yielded a mean of 0.52+/-0.20 for the segmented images, when all 2136 segmented microcalcifications were considered. Moreover, a statistical difference was observed between the AOM values for large and small microcalcifications. The proposed method had better or similar performance as compared to literature for microcalcifications with maximum diameters larger than 460MUm. For smaller microcalcifications the performance was limited. PMID- 26363677 TI - Analysis of the method for ventilation heterogeneity assessment using the Otis model and forced oscillations. AB - Increased heterogeneity of the lung disturbs pulmonary gas exchange. During bronchoconstriction, inflammation of lung parenchyma or acute respiratory distress syndrome, inhomogeneous lung ventilation can become bimodal and increase the risk of ventilator-induced lung injury during mechanical ventilation. A simple index sensitive to ventilation heterogeneity would be very useful in clinical practice. In the case of bimodal ventilation, the index (H) can be defined as the ratio between the longer and shorter time constant characterising regions of contrary mechanical properties. These time constants can be derived from the Otis model fitted to input impedance (Zin) measured using forced oscillations. In this paper we systematically investigated properties of the aforementioned approach. The research included both numerical simulations and real experiments with a dual-lung simulator. Firstly, a computational model mimicking the physical simulator was derived and then used as a forward model to generate synthetic flow and pressure signals. These data were used to calculate the input impedance and then the Otis inverse model was fitted to Zin by means of the Levenberg-Marquardt (LM) algorithm. Finally, the obtained estimates of model parameters were used to compute H. The analysis of the above procedure was performed in the frame of Monte Carlo simulations. For each selected value of H, forward simulations with randomly chosen lung parameters were repeated 1000 times. Resulting signals were superimposed by additive Gaussian noise. The estimated values of H properly indicated the increasing level of simulated inhomogeneity, however with underestimation and variation increasing with H. The main factor responsible for the growing estimation bias was the fixed starting vector required by the LM algorithm. Introduction of a correction formula perfectly reduced this systematic error. The experimental results with the dual lung simulator confirmed potential of the proposed procedure to properly deduce the lung heterogeneity level. We conclude that the heterogeneity index H can be used to assess bimodal ventilation imbalances in cases when this phenomenon dominates lung properties, however future analyses, including the impact of lung tissue viscoelasticity and distributed airway or tissue inhomogeneity on H estimates, as well as studies in the time domain, are advisable. PMID- 26363678 TI - A prototype of a novel cell phone application for tracking the vaccination coverage of children in rural communities. AB - Immunization saves millions of lives against vaccine-preventable diseases. Yet, 24 million children born every year do not receive proper immunization during their first year. UNICEF and WHO have emphasized the need to strengthen the immunization surveillance and monitoring in developing countries to reduce childhood deaths. In this regard, we present a software application called Jeev to track the vaccination coverage of children in rural communities. Jeev synergistically combines the power of smartphones and the ubiquity of cellular infrastructure, QR codes, and national identification cards. We present the design of Jeev and highlight its unique features along with a detailed evaluation of its performance and power consumption using the National Immunization Survey datasets. We are in discussion with a non-profit organization in Haiti to pilot test Jeev in order to study its effectiveness and identify socio-cultural issues that may arise in a large-scale deployment. PMID- 26363679 TI - A comparison of multiple patient reported outcome measures in identifying major depressive disorder in people with multiple sclerosis. AB - BACKGROUND: Depression is one of the most prominent and debilitating symptoms in individuals with multiple sclerosis (MS), yet there is currently no consensus on the best instruments for depression screening in MS. More head to head comparisons of available screening instruments are needed to advise MS researchers and clinicians. METHODS: A cross-sectional comparison of the effectiveness of screening for MDD using multiple patient reported outcome (PRO) screeners against a modified SCID telephone interview was completed in 164 individuals with MS. Stratum goals were set for depression levels to ensure participation by people with borderline and higher levels of depression. Criterion standard was a modified SCID MDD module. PRO measures included the PHQ 9, BDI-FS, PROMIS depression, Neuro-QOL depression, M-PHQ-2, PHQ-2, and CESD. RESULTS: 48 (29%) individuals met the modified SCID criteria for MDD. The sensitivity of the PRO measures ranged from 60% to 100% while specificity ranged from 46% to 86%. The ROC area for the PRO measures ranged from 0.79 to 0.83. Revised (higher) cutoff scores were suggested by the ROC analyses for most self reported screeners. LIMITATIONS: Enrollment was stopped early because of difficulties with recruitment. Several SCID recording could not be reviewed and diagnosis confirmed. CONCLUSIONS: CESD-10 and PHQ9 had the best diagnostic performance using optimal cutoffs, but no one PRO measure stood out as significantly better than any other. Even when revised cutoff scores were used, none of the self-reported screeners identified people with MDD with adequate accuracy. More accurate self-reported screeners would facilitate diagnosing of MDD for both research and clinical purposes. PMID- 26363680 TI - Risk of bipolar disorder among adolescents with allergic rhinitis: A nationwide longitudinal study. AB - BACKGROUND: Previous studies have suggested an immunological dysfunction in bipolar disorder, but none has investigated the temporal association between allergic rhinitis (AR) and bipolar disorder. METHODS: Using Taiwan National Health Insurance Research Database, 9506 adolescents aged 12-18 years with allergic rhinitis were enrolled between 2000 and 2008 and compared to 38,024 age and gender-matched (1:4) control groups. Subjects of bipolar disorder that occurred up to the end of follow-up (December 31, 2011) were identified. RESULTS: Adolescents with AR had a significantly higher incidence of developing bipolar disorder (0.77 vs. 0.18 per 1000 person-years, p<0.001) during the follow-up period than the controls. Adolescents with AR had an increased risk (hazard ratio [HR]: 4.62, 95% confidence interval [CI]: 3.17-6.75) of developing bipolar disorder in their later life compared to the control group after adjusting for demographic data and comorbid allergic diseases. DISCUSSION: This is the first study showing a temporal association between AR and bipolar disorder, in that patients who had AR in adolescence exhibited an increased risk of developing bipolar disorder in later life. Further study would be required to investigate the underlying mechanism about this association. PMID- 26363681 TI - Editor's perspectives - September 2015. PMID- 26363682 TI - Scalable gastroscopic video summarization via similar-inhibition dictionary selection. AB - OBJECTIVE: This paper aims at developing an automated gastroscopic video summarization algorithm to assist clinicians to more effectively go through the abnormal contents of the video. METHODS AND MATERIALS: To select the most representative frames from the original video sequence, we formulate the problem of gastroscopic video summarization as a dictionary selection issue. Different from the traditional dictionary selection methods, which take into account only the number and reconstruction ability of selected key frames, our model introduces the similar-inhibition constraint to reinforce the diversity of selected key frames. We calculate the attention cost by merging both gaze and content change into a prior cue to help select the frames with more high-level semantic information. Moreover, we adopt an image quality evaluation process to eliminate the interference of the poor quality images and a segmentation process to reduce the computational complexity. RESULTS: For experiments, we build a new gastroscopic video dataset captured from 30 volunteers with more than 400k images and compare our method with the state-of-the-arts using the content consistency, index consistency and content-index consistency with the ground truth. Compared with all competitors, our method obtains the best results in 23 of 30 videos evaluated based on content consistency, 24 of 30 videos evaluated based on index consistency and all videos evaluated based on content-index consistency. CONCLUSIONS: For gastroscopic video summarization, we propose an automated annotation method via similar-inhibition dictionary selection. Our model can achieve better performance compared with other state-of-the-art models and supplies more suitable key frames for diagnosis. The developed algorithm can be automatically adapted to various real applications, such as the training of young clinicians, computer-aided diagnosis or medical report generation. PMID- 26363683 TI - Predicting readmission risk with institution-specific prediction models. AB - OBJECTIVE: The ability to predict patient readmission risk is extremely valuable for hospitals, especially under the Hospital Readmission Reduction Program of the Center for Medicare and Medicaid Services which went into effect starting October 1, 2012. There is a plethora of work in the literature that deals with developing readmission risk prediction models, but most of them do not have sufficient prediction accuracy to be deployed in a clinical setting, partly because different hospitals may have different characteristics in their patient populations. METHODS AND MATERIALS: We propose a generic framework for institution-specific readmission risk prediction, which takes patient data from a single institution and produces a statistical risk prediction model optimized for that particular institution and, optionally, for a specific condition. This provides great flexibility in model building, and is also able to provide institution-specific insights in its readmitted patient population. We have experimented with classification methods such as support vector machines, and prognosis methods such as the Cox regression. We compared our methods with industry-standard methods such as the LACE model, and showed the proposed framework is not only more flexible but also more effective. RESULTS: We applied our framework to patient data from three hospitals, and obtained some initial results for heart failure (HF), acute myocardial infarction (AMI), pneumonia (PN) patients as well as patients with all conditions. On Hospital 2, the LACE model yielded AUC 0.57, 0.56, 0.53 and 0.55 for AMI, HF, PN and All Cause readmission prediction, respectively, while the proposed model yielded 0.66, 0.65, 0.63, 0.74 for the corresponding conditions, all significantly better than the LACE counterpart. The proposed models that leverage all features at discharge time is more accurate than the models that only leverage features at admission time (0.66 vs. 0.61 for AMI, 0.65 vs. 0.61 for HF, 0.63 vs. 0.56 for PN, 0.74 vs. 0.60 for All Cause). Furthermore, the proposed admission-time models already outperform the performance of LACE, which is a discharge-time model (0.61 vs. 0.57 for AMI, 0.61 vs. 0.56 for HF, 0.56 vs. 0.53 for PN, 0.60 vs. 0.55 for All Cause). Similar conclusions can be drawn from other hospitals as well. The same performance comparison also holds for precision and recall at top-decile predictions. Most of the performance improvements are statistically significant. CONCLUSIONS: The institution-specific readmission risk prediction framework is more flexible and more effective than the one-size-fit-all models like the LACE, sometimes twice and three-time more effective. The admission-time models are able to give early warning signs compared to the discharge-time models, and may be able to help hospital staff intervene early while the patient is still in the hospital. PMID- 26363684 TI - Repetitive peripheral magnetic stimulation to reduce pain or improve sensorimotor impairments: A literature review on parameters of application and afferents recruitment. AB - INTRODUCTION: Repetitive peripheral magnetic stimulation (rPMS over spinal root, nerve or muscle belly) is a promising technology in physiopathology research. As compared to electrical stimulation, rPMS is deemed to activate deep conductive structures and produce strong muscle contractions and massive proprioceptive afferents with minimal cutaneous recruitment. RPMS may thus act differently on neural plasticity involved in pain reduction and motor recovery in musculoskeletal or neurological conditions. However, literature is very scant and still controversial concerning afferents recruited by rPMS, thus no consensus is reached yet for its clinical use. STUDY AIM: This review dealt with stimulation parameters reported in any scientific research that applied rPMS as an intervention to improve somatosensory or motor disorders with a view of proposing recommendations for future applications. Also, controversy on afferents recruitment was discussed. RESULTS: The literature search resulted in 24 studies. Literature is scant on the topic but our review presents the rationale and the experimental data that may underlie the selection of parameters in future studies using rPMS as an intervention. Although controversy remains, the review presents that the specific recruitment of sensory afferents by magnetic stimulation may offer advantages and disadvantages depending on the pathology. CONCLUSIONS: The review proposed recommendations to improve rPMS application in clinical research. However, the development of guidelines still requires methodological and clinical studies enrolling larger samples and with randomized sham-controlled designs. PMID- 26363685 TI - Automatic detection of rhythmic and periodic patterns in critical care EEG based on American Clinical Neurophysiology Society (ACNS) standardized terminology. AB - AIMS OF THE STUDY: Continuous EEG from critical care patients needs to be evaluated time efficiently to maximize the treatment effect. A computational method will be presented that detects rhythmic and periodic patterns according to the critical care EEG terminology (CCET) of the American Clinical Neurophysiology Society (ACNS). The aim is to show that these detected patterns support EEG experts in writing neurophysiological reports. MATERIALS AND METHODS: First of all, three case reports exemplify the evaluation procedure using graphically presented detections. Second, 187 hours of EEG from 10 critical care patients were used in a comparative trial study. For each patient the result of a review session using the EEG and the visualized pattern detections was compared to the original neurophysiology report. RESULTS: In three out of five patients with reported seizures, all seizures were reported correctly. In two patients, several subtle clinical seizures with unclear EEG correlation were missed. Lateralized periodic patterns (LPD) were correctly found in 2/2 patients and EEG slowing was correctly found in 7/9 patients. In 8/10 patients, additional EEG features were found including LPDs, EEG slowing, and seizures. CONCLUSION: The use of automatic pattern detection will assist in review of EEG and increase efficiency. The implementation of bedside surveillance devices using our detection algorithm appears to be feasible and remains to be confirmed in further multicenter studies. PMID- 26363686 TI - Video-assisted thoracoscopic surgical decortication in the elderly with thoracic empyema: Five years' experience. AB - BACKGROUND: Video-assisted thoracoscopic surgery (VATS) with decortication is a major treatment for thoracic empyema in the fibropurulent stage. Compared to open thoracotomy, VATS decortication has similar efficacy but fewer postoperative complications in the treatment of thoracic empyema. The role of VATS decortication in the elderly had rarely been investigated. METHODS: From January 2006 to August 2011, we retrospectively enrolled 33 patients older than 65 years diagnosed as thoracic empyema and treated with VATS decortication. We analyzed the outcomes of this geriatric population, including surgical effectiveness, postoperative morbidity, and mortality. RESULTS: A total of 33 patients with mean age of 73.6 +/- 7.1 years received VATS decortication for their empyema. Twenty one (63.6%) patients were male. Only one patient died of progressive sepsis, due to pulmonary infection 9 days after VATS decortication. The 30-day mortality was 3% after the surgery. The major etiology (87.9%) of thoracic empyema was pneumonia. The main causes of postoperation morbidity included respiratory failure requiring mechanical ventilation for >7 days (15.2%) and septic shock (15.2%), followed by persistent air leakage for >7 days (9.1%). Twenty-four (75%) of 32 patients had good re-expansion of the affected lung 3 months after VATS decortication. CONCLUSION: We concluded that VATS decortication in the treatment of thoracic empyema is effective in elderly patients. The major concerns of postoperative complications are respiratory failure and sepsis. PMID- 26363687 TI - The benefits and risks of proton pump inhibitor therapy. PMID- 26363688 TI - [Comparison of the effectivity of oral and intra-articular administration of tenoxicam in patients with knee osteoarthritis]. AB - BACKGROUND AND OBJECTIVES: Tenoxicam is widely used in osteoarthritis treatment and we aimed to compare the effectivity of oral and intra-articular administration of tenoxicam in osteoarthritis treatment. METHODS: This study was performed between 2011 and 2012 by retrospectively analyzing and comparing the findings of 60 patients who were clinically and radiologically diagnosed with knee degenerative osteoarthritis in Bunyan state hospital pain policlinic. 60 patients included in the study were divided into two groups. The first group (tenoxicam IA, n=30) included patient findings of those subjected to intra articular injection of 20mg tenoxicam to the knee once a week for three weeks and the second group (oral tenoxicam, n=30) included patients who were administered 20mg oral tenoxicam once a day for three weeks. All patients were clinically evaluated pre-treatment and in the 1st week, 1st month and 3rd month post treatment according to specified criteria. RESULTS AND CONCLUSIONS: 22 of 60 patients included in the study were male and 38 were female. In both groups significant improvements were detected in all of the observed parameters: visual analog scale, Western Ontario McMaster Osteoarthritis Index (pain, physical activity, knee stiffness) and Lequesne index scores and in the evaluations performed in 1st week, 1st month and 3rd month with respect to pre-treatment values. Besides, a better compliance to treatment and gastrointestinal system tolerability in tenoxicam IA group was also observed. Intra-articular tenoxicam administration could be thought as an alternative treatment method in patients with knee osteoarthritis who cannot use oral tenoxicam especially due to systemic gastrointestinal system side effects and those who have difficulties in adapting to treatment. PMID- 26363689 TI - [Lidocaine alleviates propofol related pain much better than metoprolol and nitroglycerin]. AB - BACKGROUND AND OBJECTIVES: Injection pain after propofol administration is common and may disturb patients' comfort. The aim of this study was to compare effectiveness of intravenous (iv) nitroglycerin, lidocaine and metoprolol applied through the veins on the dorsum of hand or antecubital vein on eliminating propofol injection pain. METHOD: There were 147 patients and they were grouped according to the analgesic administered. Metoprolol (n=31, Group M), lidocaine (n=32, Group L) and nitroglycerin (n=29, Group N) were applied through iv catheter at dorsum hand vein or antecubital vein. Pain was evaluated by 4 point scale (0 - no pain, 1 - light pain, 2 - mild pain, 3 - severe pain) in 5, 10, 15 and 20th seconds. ASA, BMI, patient demographics, education level and the effect of pathways for injection and location of operations were analyzed for their effect on total pain score. RESULTS: There were no differences between the groups in terms of total pain score (p=0.981). There were no differences in terms of total pain score depending on ASA, education level, location of operation. However, lidocaine was more effective when compared with metoprolol (p=0.015) and nitroglycerin (p=0.001) among groups. Although neither lidocaine nor metoprolol had any difference on pain management when applied from antecubital or dorsal hand vein (p>0.05), nitroglycerin injection from antecubital vein had demonstrated statistically lower pain scores (p=0.001). CONCLUSION: We found lidocaine to be the most effective analgesic in decreasing propofol related pain. We therefore suggest iv lidocaine for alleviating propofol related pain at operations. PMID- 26363690 TI - [Comparison of the i-gelTM and the Laryngeal Mask Airway ClassicTM in terms of clinical performance]. AB - PURPOSE: The i-gelTM is one of the second generation supraglottic airway devices. Our study was designed to compare the i-gel and the Laryngeal Mask Airway ClassicTM with respect to the clinical performance. METHODS: We compared the performance of the i-gel with that of the Laryngeal Mask Airway Classic in 120 patients undergoing urologic surgery during general anesthesia without muscle relaxant with respect to the number of attempts for successful insertion, insertion time, peak airway pressure, incidence of regurgitation, fiberoptic glottic view and postoperative complications. Second generation supraglottic airway devices were inserted by the same anesthesiologist, experienced in use of both devices (>200 uses and first time failure rate <5%). Methylene blue method was used to detect gastric regurgitation. RESULTS: There was no statistical difference between the two groups regarding the success of insertion of second generation supraglottic airway device (p=0.951). The laryngeal mask insertion time for the i-gel group was significantly shorter than that for the Laryngeal Mask Airway Classic group (11.6+/-2.4s versus 13.1+/-1.8s [p=0.001]). The fiberoptic glottic view scores for the i-gel group was significantly better than that for the ones for the Laryngeal Mask Airway Classic group (p=0.001). On fiberoptic view, there was no sign of methylene blue dye at any time point in either group. In addition, there was no difference between the groups in patient response regarding the presence of a sore throat when questioned 24h after the procedure (p=0.752). CONCLUSION: Both devices had good performance with low postoperative complications and without occurrence of regurgitation. The i-gel provided a shorter insertion time and a better fiberoptic view than the Laryngeal Mask Airway Classic. PMID- 26363691 TI - [Effectiveness of sub-Tenon's block in pediatric strabismus surgery]. AB - BACKGROUND AND OBJECTIVES: Strabismus surgery is a frequently performed pediatric ocular procedure. A frequently occurring major problem in patients receiving this treatment involves the oculocardiac reflex. This reflex is associated with an increased incidence of postoperative nausea, vomiting, and pain. The aim of this study was to investigate the effects of a sub-Tenon's block on the oculocardiac reflex, pain, and postoperative nausea and vomiting. METHODS: 40 patients aged 5 16 years with American Society of Anesthesiologists status I-II undergoing elective strabismus surgery were included in this study. Patients included were randomly assigned into two groups by using a sealed envelope method. In group 1 (n=20), patients did not receive sub-Tenon's anesthesia. In group 2 (n=20), following intubation, sub-Tenon's anesthesia was performed with the eye undergoing surgery. Atropine use, pain scores, oculocardiac reflex, and postoperative nausea and vomiting incidences were compared between groups. RESULTS: There were no significant differences between groups with regard to oculocardiac reflex and atropine use (p>0.05). Pain scores 30min post-surgery were significantly lower in group 2 than in group 1 (p<0.05). Additional analgesic needed during the postoperative period was significantly lower in group 2 compared to group 1 (p<0.05). CONCLUSIONS: In conclusion, we think that a sub Tenon's block, combined with general anesthesia, is not effective and reliable in decreasing oculocardiac reflex and postoperative nausea and vomiting. However, this method is safe for reducing postoperative pain and decreasing additional analgesia required in pediatric strabismus surgery. PMID- 26363692 TI - [Changes in the distance between carina and orotracheal tube during open or videolaparoscopic bariatric surgery]. AB - OBJECTIVE: To examine whether there are changes in the distance between the orotracheal tubeand carina induced by orthostatic retractor placement or by pneumoperitoneum insufflation in obese patients undergoing gastroplasty. METHODS: 60 patients undergoing bariatric surgery by two techniques: open (G1) or videola paroscopic (G2) gastroplasty were studied. After tracheal intubation, adequate ventilation of both hemitoraxes was confirmed by lung auscultation. The distance orotracheal tube-carina was estimated with the use of a fiber bronchoscope before and after installation of orthostatic retractors in G1 or before and after insufflation of pneumoperitoneum in patients in G2. RESULTS: G1 was composed of 22 and G2 of 38 patients. No cases of endobronchial intubationwere detected in either group. The mean orotracheal tube-carina distance variation was estimated in -0.03 cm (95% CI 0.06 to -0.13) in the group of patients undergoing open gastroplastyand in -0.42 cm (95% CI -0.56 to -1.4) in the group of patients undergoing videolaparoscopic gastroplasty. The extremes of variation in each group were: 0.5 cm to -1.6 cm in patients under-going open surgery and 0.1 cm to 2.2 cm in patients undergoing videolaparoscopic surgery. CONCLUSIONS: There was no significant change in orotracheal tube-CA distance after placementof orthostatic retractors in patients undergoing open gastroplasty. There was a reduction inorotracheal tube-CA distance after insufflation of pneumoperitoneum in patients undergoing videolaparoscopic gastroplasty. We recommend attention to lung auscultation and to signals of ventilation monitoring and reevaluation of orotracheal tube placement after peritoneal insufflation. PMID- 26363693 TI - [Adverse respiratory events after general anesthesia in patients at high risk of obstructive sleep apnea syndrome]. AB - INTRODUCTION: Patients with STOP-BANG score >3 have a high risk of Obstructive sleep apnea. The aim of this study was to evaluate early postoperative respiratory complications in adults with STOP-BANG score >3 after general anesthesia. METHODS: This is a prospective double cohort study matching 59 pairs of adult patients with STOP-BANG score >3 (high risk of obstructive sleep apnea) and patients with STOP-BANG score <3 (low risk of obstructive sleep apnea), similar with respect to gender, age and type of surgery, admitted after elective surgery in the Post-Anaesthesia Care Unit in May 2011. Primary outcome was the development of adverse respiratory events. Demographics data, perioperative variables, and postoperative length of stay in the Post-Anesthesia Care Unit and in hospital were recorded. The Mann-Whitney test, the chi-square test and the Fisher exact test were used for comparisons. RESULTS: Subjects in both pairs of study subjects had a median age of 56 years, including 25% males, and 59% were submitted to intra-abdominal surgery. High risk of obstructive sleep apnea patients had a higher median body mass index (31 versus 24kg/m(2), p<0.001) and had more frequently co-morbidities, including hypertension (58% versus 24%, p<0.001), dyslipidemia (46% versus 17%, p<0.001) and insulin-treated diabetes mellitus (17% versus 2%, p=0.004). These patients were submitted more frequently to bariatric surgery (20% versus 2%, p=0.002). Patients with high risk of obstructive sleep apnea had more frequently adverse respiratory events (39% versus 10%, p<0.001), mild to moderate desaturation (15% versus 0%, p=0.001) and inability to breathe deeply (34% versus 9%, p=0.001). CONCLUSION: After general anesthesia high risk of obstructive sleep apnea patients had an increased incidence of postoperative respiratory complications. PMID- 26363694 TI - [Ketamine-propofol sedation in circumcision]. AB - BACKGROUND AND OBJECTIVE: to compare the therapeutic effects of ketamine alone or ketamine plus propofol on analgesia, sedation, recovery time, side effects in premedicated children with midazolam-ketamine-atropin who are prepared circumcision operation. METHODS: 60 American Society of Anaesthesiologists physical status I-II children, aged between 3 and 9 years, undergoing circumcision operations under sedation were recruited according to a randomize and double-blind institutional review board-approved protocol. Patients were randomized into two groups via sealed envelope assignment. Both groups were administered a mixture of midazolam 0.05mg/kg+ketamine 3mg/kg+atropine 0.02mg/kg intramuscularly in the presence of parents in the pre-operative holding area. Patients were induced with propofol-ketamine in Group I or ketamine alone in Group II. RESULTS: in the between-group comparisons, age, weight, initial systolic blood pressure, a difference in terms of the initial pulse rate was observed (p>0.050). Initial diastolic blood pressure and subsequent serial measurements of 5, 10, 15, 20thmin, systolic blood pressure, diastolic blood pressure and pulse rate in ketamine group were significantly higher (p<0.050). CONCLUSION: propofol-ketamine (Ketofol) provided better sedation quality and hemodynamy than ketamine alone in pediatric circumcision operations. We did not observe significant complications during sedation in these two groups. Therefore, ketofol appears to be an effective and safe sedation method for circumcision operation. PMID- 26363695 TI - [Perioperative morbidity and mortality in the first year of life: a systematic review (1997-2012)]. AB - BACKGROUND AND OBJECTIVES: Although many recognize that the first year of life and specifically the neonatal period are associated with increased risk of anesthetic morbidity and mortality, there are no studies directed to these pediatric subpopulations. This systematic review of the scientific literature including the last 15 years aimed to analyze the epidemiology of morbidity and mortality associated with general anesthesia and surgery in the first year of life and particularly in the neonatal (first month) period. CONTENT: The review was conducted by searching publications in Medline/PubMed databases, and the following outcomes were evaluated: early mortality in the first year of life (<1 Yr) and in subgroups of different vulnerability in this age group (0-30 days and 1-12 months) and the prevalence of cardiac arrest and perioperative critical/adverse events of various types in the same subgroups. CONCLUSIONS: The current literature indicates great variability in mortality and morbidity in the age group under consideration and in its subgroups. However, despite the obvious methodological heterogeneity and absence of specific studies, epidemiological profiles of morbidity and mortality related to anesthesia in children in the first year of life show higher frequency of morbidity and mortality in this age group, with the highest peaks of incidence in the neonates' anesthesia. PMID- 26363696 TI - [Treatment of status migrainosus by general anesthesia: a case report]. AB - BACKGROUND AND OBJECTIVES: The status migrainosus is a complication of migraine characterizedby severe headache for more than 72 h that did not respond to treatment, with risk of strokeand suicide. Researches on treatment are directed to drugs that stimulate GABA receptors; propofol and isoflurane act on sub-GABAa receptors and theoretically could be interesting. The first has been the subject of research in severe migraine. Opioids are employed in pain, and its use in chronic headache is debatable, but these agents are employed in acute cases. The goalis to present a case of refractory status migrainosus in that we decided to break the pain cycle by general anesthesia. CASE REPORT: Female patient, aged 50 years, with status migrainosus, in the last five days withvisits to the emergency department, medicated parenterally with various agents without result. Without comorbidities, dehydrated, described her pain as "well over 10" in Visual NumericScale (VNS). After consulting the literature, and given the apparent severity of the condition, we opted for a general anesthesia: induction with fentanyl, propofol, and vecuroniumand maintenance with isoflurane and propofol for two hours. Following the treatment, in the postanesthetic recuperation (PAR), the patient related her pain as VNS 3, and was released after five hours with VNS 2. Subsequently, her preventive treatment was resumed. CONCLUSION: Status migrainosus is a rare disabling complication and anesthetics have been the subject of research in its treatment; the option for general anesthesia with agents that stimulate GABA receptors, propofol and isoflurane, in association with fentanyl, proved effective and should encourage new research. PMID- 26363697 TI - ["Loss of breath" as a cause of postoperative hypoxia and bradycardia in children submitted to tonsillectomy]. AB - BACKGROUND AND OBJECTIVES: The "shortness of breath" or "breathing interruption" crisis can be considered a cause of hypoxia in childhood. It is characterized by the presence of a triggering factor followed by weeping and apnea in expiration accompanied by cyanosis or pallor. The sequence of events may include bradycardia, loss of consciousness, abnormal postural toneand even asystole. A review of the literature revealed only two reports of postoperative apneacaused by "shortness of breath". CASE REPORT: This article describes the case of a child with a history of "shortness of breath" undiagnosed before the adenotonsillectomy, but that represented the cause of episodes of hypoxemia and bradycardia in the postoperative period. CONCLUSIONS: the "shortness of breath" crisis should be considered as a possible cause of perioperative hypoxia in children, especially when there is a history suggestive of this problem. As some events may be accompanied by bradycardia, loss of consciousness, abnormal postural tone and even asystole, observation in a hospital setting should be considered. PMID- 26363698 TI - [Anaesthesia for infant with Jarcho Levin syndrome: case report]. AB - Jarcho Levin syndrome is a rare disorder. There are various vertebral and costal anomalies. Severe deformities and abnormal fusion of ribs and vertebrae cause respiratory insufficiency and pneumonia. We present anaesthesia in a patient with Jarcho Levin syndrome for vesicoureteral reflux. PMID- 26363699 TI - [Life-threatening acute subdural haematoma after combinedspinal-epidural anaesthesia in labour]. AB - BACKGROUND AND OBJECTIVES: Only few reports in literature have pointed out to the possibility of a cranial subdural haematoma formation associated with dural puncture during spinal orepidural analgesia. We herein describe such a rare case who was diagnosed to have acute subdural haematoma after combined spinal-epidural anaesthesia used in labour. CASE REPORT: A 34-year-old, primigravid women with a gestation of 38 weeks underwent cae-sarean section under combined spinal-epidural anaesthesia and gave birth to a healthy boy. Thirty-two hours after delivery, her moderate headache progressed to a severe headache associated with nausea and vomiting and later was more complicated with a generalized tonic-clonic seizure and ensuing lethargy. Computed tomography of the brain demonstrated a right-sided fronto-temporo-parietal acute subdural haematoma with diffuse cerebral oedema. She under-went urgent FTP craniotomy and evacuation of the haematoma. Early postoperative cranial computed tomography showed a clean operative site. Eight days after subdural haematoma surgery, she became lethargic again, and this time cranial computed tomography disclosed anextradural haematoma under the bone flap for which she had to undergo surgery again. Two days later, she was discharged home with Karnofsky performance score of 90/100. At follow-up exam, she was neurologically intact and her cranial computed tomography and magnetic resonance were normal. CONCLUSIONS: As conclusion, with the use of this combined spinal epidural anaesthesia, it should be kept in mind that headache does not always mean low pressure headache associated with spinal anaesthesia and that a catastrophic complication of subdural haematoma may also occur. PMID- 26363700 TI - [Letter to the editor commenting the study published in the journal by Ascedio Jose Rodrigues et al. (Rev Bras Anestesiol 2013,63(4):358-361), regarding intubation with flexible bronchoscope]. PMID- 26363702 TI - Knitting up the ravelled sleeve of care: sleep and psychosis. PMID- 26363701 TI - Efficacy of cognitive behavioural therapy for sleep improvement in patients with persistent delusions and hallucinations (BEST): a prospective, assessor-blind, randomised controlled pilot trial. AB - BACKGROUND: Sleep disturbance occurs in most patients with delusions or hallucinations and should be treated as a clinical problem in its own right. However, cognitive behavioural therapy (CBT)-the best evidence-based treatment for insomnia-has not been tested in this patient population. We aimed to pilot procedures for a randomised trial testing CBT for sleep problems in patients with current psychotic experiences, and to provide a preliminary assessment of potential benefit. METHODS: We did this prospective, assessor-blind, randomised controlled pilot trial (Better Sleep Trial [BEST]) at two mental health centres in the UK. Patients (aged 18-65 years) with persistent distressing delusions or hallucinations in the context of insomnia and a schizophrenia spectrum diagnosis were randomly assigned (1:1), via a web-based randomisation system with minimisation to balance for sex, insomnia severity, and psychotic experiences, to receive either eight sessions of CBT plus standard care (medication and contact with the local clinical team) or standard care alone. Research assessors were masked to group allocation. Assessment of outcome was done at weeks 0, 12 (post treatment), and 24 (follow-up). The primary efficacy outcomes were insomnia assessed by the Insomnia Severity Index (ISI) and delusions and hallucinations assessed by the Psychotic Symptoms Rating Scale (PSYRATS) at week 12. We did analysis by intention to treat, with an aim to provide confidence interval estimation of treatment effects. This study is registered with ISRCTN, number 33695128. FINDINGS: Between Dec 14, 2012, and May 22, 2013, and Nov 7, 2013, and Aug 26, 2014, we randomly assigned 50 patients to receive CBT plus standard care (n=24) or standard care alone (n=26). The last assessments were completed on Feb 10, 2015. 48 (96%) patients provided follow-up data. 23 (96%) patients offered CBT took up the intervention. Compared with standard care, CBT led to reductions in insomnia in the large effect size range at week 12 (adjusted mean difference 6.1, 95% CI 3.0-9.2, effect size d=1.9). By week 12, nine (41%) of 22 patients receiving CBT and one (4%) of 25 patients receiving standard care alone no longer had insomnia, with ISI scores lower than the cutoff for insomnia. The treatment effect estimation for CBT covered a range from reducing but also increasing delusions (adjusted mean difference 0.3, 95% CI -2.0 to 2.6) and hallucinations ( 1.9, -6.5 to 2.7). Three patients, all in the CBT group, had five adverse events, although none were regarded as related to study treatment. INTERPRETATION: Our findings show that CBT for insomnia might be highly effective for improving sleep in patients with persistent delusions or hallucinations. A larger, suitably powered phase 3 study is now needed to provide a precise estimate of the effects of CBT for sleep problems, both on sleep and psychotic experiences. FUNDING: Research for Patient Benefit Programme, National Institute for Health Research. PMID- 26363704 TI - Care workers health in Swiss nursing homes and its association with psychosocial work environment: A cross-sectional study. AB - BACKGROUND: Previous studies have demonstrated poor health of care workers in nursing homes. Yet, little is known about the prevalence of physical and mental health outcomes, and their associations with the psychosocial work environment in nursing homes. OBJECTIVES: (1) To explore the prevalence of physical and mental health outcomes of care workers in Swiss nursing homes, (2) their association with psychosocial work environment. METHODS: This is a secondary data analysis of the cross-sectional Swiss Nursing Home Human Resources Project (SHURP). We used survey data on socio-demographic characteristics and work environment factors from care workers (N=3471) working in Swiss nursing homes (N=155), collected between May 2012 and April 2013. GEE logistic regression models were used to estimate the relationship between psychosocial work environment and physical and mental health outcomes, taking into account care workers' age. RESULTS: Back pain (19.0%) and emotional exhaustion (24.2%) were the most frequent self-reported physical and mental health. Back pain was associated with increased workload (odds ratios (OR) 1.52, confidence interval (CI) 1.29-1.79), conflict with other health professionals and lack of recognition (OR 1.72, CI 1.40-2.11), and frequent verbal aggression by residents (OR 1.36, CI 1.06-1.74), and inversely associated with staffing adequacy (OR 0.69, CI 0.56-0.84); emotional exhaustion was associated with increased workload (OR 1.96, CI 1.65-2.34), lack of job preparation (OR 1.41, CI 1.14-1.73), and conflict with other health professionals and lack of recognition (OR 1.68, CI 1.37-2.06), and inversely associated with leadership (OR 0.70, CI 0.56-0.87). CONCLUSIONS: Physical and mental health among care workers in Swiss nursing homes is of concern. Modifying psychosocial work environment factors offer promising strategies to improve health. Longitudinal studies are needed to conduct targeted assessments of care workers health status, taking into account their age, along with the exposure to all four domains of the proposed WHO model. PMID- 26363703 TI - [Mammary duct ectasia in children: A case report]. AB - INTRODUCTION: Bloody nipple discharge is an infrequent symptom during childhood. The most common cause in this population is mammary duct ectasia (MDE), which is a benign and self-limiting condition, that is characterized by dilatation of the mammary ducts, fibrosis and periductal inflammation. OBJECTIVE: Report of a case of MDE in order to improve physicians' diagnosis accuracy and avoid aggressive studies and treatments. CASE REPORT: Six-months old male healthy infant, exclusively breastfeeded, that visited our clinic with a lump beneath his right nipple and bloody discharge from the same nipple. An ultrasound was performed which showed a multicystic lesion suggestive of MDE. Watchful waiting was decided as treatment, with good evolution after six months of follow up. CONCLUSIONS: The MDE is the leading cause of bloody discharge in pediatric population, being a benign condition that resolves spontaneously before nine months. The knowledge of this condition is essential so as to accurately diagnose and treat it. PMID- 26363705 TI - Using sense-making theory to aid understanding of the recognition, assessment and management of pain in patients with dementia in acute hospital settings. AB - BACKGROUND: The recognition, assessment and management of pain in hospital settings is suboptimal, and is a particular challenge in patients with dementia. The existing process guiding pain assessment and management in clinical settings is based on the assumption that nurses follow a sequential linear approach to decision making. In this paper we re-evaluate this theoretical assumption drawing on findings from a study of pain recognition, assessment and management in patients with dementia. AIM: To provide a revised conceptual model of pain recognition, assessment and management based on sense-making theories of decision making. METHODS: The research we refer to is an exploratory ethnographic study using nested case sites. Patients with dementia (n=31) were the unit of data collection, nested in 11 wards (vascular, continuing care, stroke rehabilitation, orthopaedic, acute medicine, care of the elderly, elective and emergency surgery), located in four NHS hospital organizations in the UK. Data consisted of observations of patients at bedside (170h in total); observations of the context of care; audits of patient hospital records; documentary analysis of artefacts; semi-structured interviews (n=56) and informal open conversations with staff and carers (family members). FINDINGS: Existing conceptualizations of pain recognition, assessment and management do not fully explain how the decision process occurs in clinical practice. Our research indicates that pain recognition, assessment and management is not an individual cognitive activity; rather it is carried out by groups of individuals over time and within a specific organizational culture or climate, which influences both health care professional and patient behaviour. CONCLUSIONS: We propose a revised theoretical model of decision making related to pain assessment and management for patients with dementia based on theories of sense-making, which is reflective of the reality of clinical decision making in acute hospital wards. The revised model recognizes the salience of individual cognition as well as acknowledging that decisions are constructed through social interaction and organizational context. The model will be used in further research to develop decision support interventions to assist with the assessment and management of patients with dementia in acute hospital settings. PMID- 26363706 TI - The Development of Cortical Microinfarcts Is Associated with Intracranial Atherosclerosis: Data from the Chinese Intracranial Atherosclerosis Study. AB - BACKGROUND: Little is known about the association between the cortical microinfarcts (CMIs) and intracranial atherosclerosis (ICAS) in Chinese patients with ischemic stroke. This study was designed to analyze the association and evaluate the role of CMIs in clinical outcomes. METHODS: We evaluated 1421 consecutive patients who had experienced an acute cerebral ischemia within 7 days after symptom onset and evaluated the presence of CMIs and ICAS based on patients' 3.0-T magnetic resonance imaging and magnetic resonance angiography scans. Baseline characteristics, patient risk factors, and clinical outcomes were analyzed to investigate the different outcomes between the CMIs (n = 209) group and non-CMIs (n = 1212) group. RESULTS: CMIs were present in 14.7% persons. The following parameters were associated with risk of CMIs: advanced age, National Institutes of Health Stroke Scale score on admission, lower level of systemic blood pressure, lower triglycerides level, ICAS, and cerebral microbleeds (CMBs). On multivariate logistic regression analysis, ICAS remained an independent risk factor for the development of CMIs (adjusted odds ratio, 1.493; 95% confidence interval, 1.022-2.182; P = .038). At the time point of 1 year after stroke, the rates of poor outcome (modified Rankin Scale, 3-6) in CMIs group (33.5%) were statistically significantly different from the non-CMIs group (22.6%; P = .001). In addition, patients in CMIs group had a significantly higher stroke recurrence rate than patients in the non-CMIs group (6.7% versus 4%; P = .085). CONCLUSIONS: The development of CMIs is strongly associated with ICAS. CMIs are independent predictors of poor prognosis in patients with ischemic stroke. PMID- 26363707 TI - Metabolic Syndrome Predicts Refractoriness to Intravenous Thrombolysis in Acute Ischemic Stroke. AB - BACKGROUND: Metabolic syndrome (MetS) has been associated with higher resistance to clot lysis at 24 hours after tissue plasminogen activator (tPA) administration in patients with acute ischemic stroke. We aimed to test this hypothesis at earlier time points, when neurointerventional rescue procedures may still be indicated to achieve arterial recanalization. METHODS: This is a prospective and observational study in consecutive stroke patients with MCA occlusion treated with IV tPA. MetS was diagnosed following the unified criteria of the last Joint Interim Statement 2009 participating several major organizations. The primary outcome variable was resistance to thrombolysis, defined as the absence of complete middle cerebral artery recanalization 2 hours after tPA bolus assessed by transcranial color-coded duplex or when rescue mechanical thrombectomy after IV tPA was required. Secondary outcome variables were dramatic neurological improvement (decrease in >=10 points, or a National Institutes of Health Stroke Scale [NIHSS] score of 0-1 at 24 hours), symptomatic intracerebral hemorrhage following European-Australasian Acute Stroke Study II criteria, infarct volume at 24 hours (calculated by using the formula for irregular volumes, ABC/2), and good outcome (modified Rankin Scale score < 3) at 3 months. RESULTS: A total of 234 patients (median baseline NIHSS score 16 [10-20]) were included and 146 (62.4%) fulfilled MetS criteria. After multivariate analysis, MetS emerged as an independent predictor of resistance to thrombolysis (odds ratio = 2.2 [1.3-4.2], P = .01) and absence of dramatic neurological improvement (odds ratio = .5 [.28 .97], P = .04). In addition, MetS conferred poorer functional outcome, higher symptomatic intracerebral hemorrhage rate, and increased infarct volume, although these associations disappeared after adjustment for covariates. CONCLUSIONS: MetS predicts patients with middle cerebral artery occlusion refractory to early clot dissolution after IV tPA. This finding may help in acute clinical decision making. PMID- 26363709 TI - Omics Approach to Identify Factors Involved in Brassica Disease Resistance. AB - Understanding plant's defense mechanisms and their response to biotic stresses is of fundamental meaning for the development of resistant crop varieties and more productive agriculture. The Brassica genus involves a large variety of economically important species and cultivars used as vegetable source, oilseeds, forage and ornamental. Damage caused by pathogens attack affects negatively various aspects of plant growth, development, and crop productivity. Over the last few decades, advances in plant physiology, genetics, and molecular biology have greatly improved our understanding of plant responses to biotic stress conditions. In this regard, various 'omics' technologies enable qualitative and quantitative monitoring of the abundance of various biological molecules in a high-throughput manner, and thus allow determination of their variation between different biological states on a genomic scale. In this review, we have described advances in 'omic' tools (genomics, transcriptomics, proteomics and metabolomics) in the view of conventional and modern approaches being used to elucidate the molecular mechanisms that underlie Brassica disease resistance. PMID- 26363708 TI - [An anorectal lesion: An unexpected association!]. PMID- 26363710 TI - Feasibility of Automated Three-Dimensional Rotational Mechanics by Real-Time Volume Transthoracic Echocardiography: Preliminary Accuracy and Reproducibility Data Compared with Cardiovascular Magnetic Resonance. AB - BACKGROUND: Three-dimensional (3D) speckle-tracking echocardiography (STE) for myocardial strain imaging may be superior to two-dimensional STE, especially with respect to rotational mechanics. Automated strain measurements from nonstitched 3D STE may improve work flow and clinical utility. The aim of this study was to test the feasibility of model-based 3D STE for the automated measurement of voxel circumferential strain (Ecc) and myocardial rotation. METHODS: Thirty-five individuals (12 healthy volunteers, 12 patients with dilated cardiomyopathy, and 11 patients with hypertensive left ventricular [LV] hypertrophy) were prospectively studied. The latter two groups did not have significant coronary artery disease on coronary arteriography. Tagged cardiovascular magnetic resonance (CMR) and feature-tracking CMR were used as reference standards. Regional (apex and mid left ventricle) and slice (within a region) Ecc and rotation were measured by real-time volume transthoracic echocardiography (nonstitched) using an automated algorithm. RESULTS: Compared with both CMR techniques, apical and mid-LV Ecc (concordance correlation coefficients [CCCs], 0.84-0.95 and 0.48-0.68) and rotation (CCCs, 0.70-0.95 and 0.42-0.68) showed excellent, good, and moderate agreement, respectively. At the LV base, rotation showed poor agreement with CMR methods (CCC, 0.04-0.21), consistent with previous descriptions, but calculated LV twist showed moderate to good correlation with CMR techniques (CCC, 0.61-0.84). However, the 95% CI for measurements between techniques was wide, emphasizing the challenges in comparing voxel deformation by 3D echocardiography with CMR, compounded by differences in approaches to measuring deformation, and matching regional and slice measurements between techniques. Reproducibility (n = 10, including test-retest variability) of automated 3D strain and rotation measurements was good to excellent (coefficient of variation < 10%) and was comparable with that of CMR methods (coefficient of variation < 10%) in the same patients. CONCLUSIONS: The data from this study show that automated measurements of voxel rotational mechanics by real-time volume transthoracic echocardiography is feasible and comparable with tagged CMR and feature-tracking CMR strain measurements, albeit with wide limits of agreement, emphasizing the differences between the modalities. Furthermore, this automated 3D speckle-tracking echocardiographic approach shows excellent reproducibility, including test-retest variability, comparable with that of the CMR methods. PMID- 26363711 TI - Profiling Individual Surgeon Performance Using Information from a High-Quality Clinical Registry: Opportunities and Limitations. AB - BACKGROUND: There is increasing interest in profiling the quality of individual medical providers. Valid assessment of individuals should highlight improvement opportunities, but must be considered in the context of limitations. STUDY DESIGN: High quality clinical data from the American College of Surgeons NSQIP, gathered in accordance with strict policies and specifications, was used to construct individual surgeon-level assessments. There were 39,976 cases evaluated, performed by 197 surgeons across 9 hospitals. Both 2-level (cases by surgeon) and 3-level (cases by surgeon by hospital) risk-adjusted, hierarchical regression analyses were performed. Outcomes were 30-day postoperative morbidity, surgical site infection, and mortality. Surgeon performance was compared in both absolute and relative terms. "Signal-to-noise" reliability was calculated for surgeons and models. Projected case requirements for reliability levels were generated. RESULTS: Surgeon performances could be distinguished to different degrees: morbidity distinguished best, mortality least. Outliers could be identified for morbidity and infection, but not mortality. Reliability was also highest for morbidity and lowest for mortality. Even models with high overall reliability did not assess all providers reliably. Incorporating institutional effects had predictable effects: penalizing providers at "good" institutions, benefiting providers at "poor" institutions. CONCLUSIONS: Individual surgeon profiles can, at times, be distinguished with moderate or good reliability, but to different degrees in different models. Absolute and relative comparisons are feasible. Incorporating institutional level effects in individual provider modeling presents an interesting policy dilemma, appearing to benefit providers at "poor-performing" institutions, but penalizing those at "high-performing" ones. No portrayal of individual medical provider quality should be accepted without consideration of modeling rationale and, critically, reliability. PMID- 26363712 TI - Resident education in robotic-assisted vertical sleeve gastrectomy: outcomes and cost-analysis of 411 consecutive cases. AB - BACKGROUND: Robotic technology is increasingly prevalent in bariatric surgery, yet there are national deficiencies in exposure of surgical residents to robotic techniques. OBJECTIVES: The purpose of this study is to accurately characterize the perioperative outcomes of a resident teaching model using the robotic assisted sleeve gastrectomy. SETTING: University Hospital. METHODS: We identified 411 consecutive patients who underwent robotic sleeve gastrectomy at our institution from a prospectively maintained administrative database. Perioperative morbidity, operative time, and supply cost of the procedure were analyzed. RESULTS: Mean operative time was 96.4+/-24.9 minutes; mean robot usage time was 63.9 minutes (range 30.0-122.0 min). Ninety-day morbidities included reoperation (0.72%), major bleeding complications (0.48%), staple line leak (0.24%), stricture (0.97%), need for blood transfusion (3.86%), surgical site infection (1.69%), deep vein thrombosis (0.48%), and pulmonary embolism (0.48%). Mortality was nil. The resident cohort achieved operative time plateaus after five consecutive cases. Subset analysis for fiscal year 2014 demonstrated significantly increased supply cost for robotic sleeve gastrectomy compared with its laparoscopic equivalent. CONCLUSION: Robotic-assisted sleeve gastrectomy can be instituted as a model for resident robotic education with rates of morbidity and operative times equivalent to historical laparoscopic controls. The robot's enhanced ergonomics and its opportunity for resident education must be weighed against its increased supply cost. PMID- 26363713 TI - Detailed anatomy of staple line crossings in sleeve gastrectomies for morbid obesity. PMID- 26363714 TI - Postoperative marijuana use and disordered eating among bariatric surgery patients. AB - BACKGROUND: Current literature is scarce in documenting marijuana use after bariatric weight loss surgery (WLS). OBJECTIVES: The objective of this study was to explore the association among marijuana use patterns, disordered eating, and food addiction behaviors in patients 2 years after WLS. SETTING: A university hospital in the United States. METHODS: Participants (N = 50, mean age 28 y, standard deviation = 5.8) were administered a structured assessment that included the Addiction Severity Index, Yale Food Addiction Scale, Eating Disorder Examination Questionnaire, and Disordered Eating Questionnaire. Marijuana use was defined based on the Addiction Severity Index as current use (within 30 d), recent use (use in last year), and increased use (increased use since surgery). Data were analyzed using Fisher's exact tests and linear regression methods adjusting for age, gender, race/ethnicity, time since surgery, and change in body mass index. RESULTS: The majority of the sample was female (76%) and underwent Roux-en-Y gastric bypass (62%). Eighteen percent (18%) of the sample reported current marijuana use; 38% reported recent use; and 21.4% reported increased use post-WLS. A loss of controlled food intake was associated with current (P = .02) and increased post-WLS use (P = .01). Increased use and/or regular marijuana use predicted higher scores on eating disorder subscales compared with respective counterparts (P<.05). Current use did not significantly predict higher scores on the Yale Food Addiction Scale. CONCLUSIONS: Findings indicated marijuana use in post-WLS patients despite recommendations against use. A subgroup of WLS patients may be at risk for disordered eating post-WLS, particularly those who used marijuana before surgery, and should be closely monitored for several years post WLS. PMID- 26363715 TI - Early outcomes of laparoscopic sleeve gastrectomy in a multiethnic Asian cohort. AB - BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) has become a popular bariatric operation worldwide. OBJECTIVES: To report early outcomes of patients with LSG performed. SETTINGS: University hospital and a restructured hospital, Singapore. METHODS: Data of patients who underwent LSG as a primary procedure from 2008 to 2013 were analyzed for change in body mass index (BMI), percentage of weight loss (%WL), and percentage of excess weight loss (%EWL). The remission of obesity related co-morbidities after LSG was analyzed. Logistic regression analyses were performed to determine predictive factors for perioperative complication and suboptimal EWL. RESULTS: Two hundred operations were performed on a cohort that consisted of 74 Chinese, 57 Malay, and 52 Indian patients and 17 patients from other ethnic groups. Mean preoperative weight and BMI were 118.1+/-26.8 kg and 43.0+/-8.0 kg/m(2), respectively. Mean follow-up duration was 16.7+/-9.4 months. At 6, 12, 24 and 36 months, the percentage of patients followed-up were 79.5%, 75.7%, 50.0%, and 50.0%, and the mean %EWL were 51.2%, 61.2%, 60.9%, and 51.0%, respectively. Postoperative complications occurred in 9 patients (4.5%), 5 of whom (2.5%) required reoperation. There was no mortality in our series. Remission of type 2 diabetes mellitus (T2DM) was significantly associated with achieving>50% EWL (P = .009). Patients>50 years of age and higher preoperative BMI were significant factors for failure to achieve>50% EWL at 1 year after LSG. CONCLUSION: LSG is a safe and effective operation for achieving significant weight loss and improvement of co-morbidities in multiethnic Asian population. Adequate EWL is important to achieve remission of T2DM. Older patients and higher preoperative BMI are predictive factors for suboptimal EWL. PMID- 26363716 TI - Bariatric surgery: a viable treatment option for patients with severe mental illness. AB - BACKGROUND: Although bariatric surgery has become a recognized treatment for obesity, its utility among patients with severe psychiatric disorders has not been extensively studied. A few studies have reported similar weight loss outcomes in these patients, but psychiatric status after bariatric surgery has been studied only minimally, and it is unknown if exacerbation of the mental illness affects weight loss. OBJECTIVES: The aim of this study was to shed greater light on the issue of serious mental illness and bariatric surgery. Specifically, do patients with a diagnosis of schizophrenia, bipolar I, and bipolar II have poorer weight loss outcomes postbariatric surgery than the general bariatric surgery population? Also, do patients with these diagnoses experience an exacerbation of psychiatric symptoms after bariatric surgery, and if so, is the exacerbation of these disorders linked to poorer weight loss results? SETTING: Midwest university medical center. METHODS: A medical record review of approximately 1500 bariatric patients in a Midwest university medical center was conducted to identify those patients with diagnoses of schizophrenia, bipolar I, and bipolar II. Information was gathered on bariatric surgery outcomes and changes in psychiatric status postsurgery. RESULTS: Eighteen patients were identified as undergoing bariatric surgery and having a diagnosis of schizophrenia, bipolar I, or bipolar II. Weight loss in this group was significant and comparable to expected outcomes of absolute weight lost, changes in body mass index, and percentage excess weight loss for patients in the typical bariatric population. Postsurgery psychiatric status was known on 10 patients. All 10 patients experienced some exacerbation of psychiatric problems yet weight loss outcomes were still as expected. CONCLUSION: Bariatric surgery is a viable obesity treatment option for patients with schizophrenia, bipolar I, and bipolar II disorders. Symptom exacerbations occurred postsurgery, although it is not clear if these were due to the surgery or would have occurred in the normal course of the illness. PMID- 26363717 TI - Variation in the use of minimally invasive bariatric surgery. AB - BACKGROUND: Obesity is a significant public health problem in the United States. Despite the known benefits of bariatric surgery, most patients eligible for bariatric surgery do not receive it. Access to minimally invasive bariatric surgery (MIS), the surgical gold standard, may be a limitation. OBJECTIVES: We investigated geographic variation in the utilization of laparoscopy for bariatric surgical procedures. METHODS: We utilized a unique 3-state inpatient database. Adult patients receiving initial bariatric surgery were included. Patients were divided into hospital service areas (HSAs). Rates of MIS utilization in each HSA were calculated. HSAs were divided into quintiles of utilization. Patient and hospital characteristics were compared across quintiles. RESULTS: Over the 5-year study period, 127,008 patients received bariatric surgery. MIS technology was available in all HSAs. MIS was performed in 88.4% of procedures and was performed in 70.6% of patients in the lowest quintile compared with 97.0% in the highest (P<.01). The use of laparoscopy across quintiles varied significantly by rural hospital status: All 7 rural hospitals were located in the lowest quintile of utilization. CONCLUSION: Variation in the performance of MIS bariatric surgical procedures exists. These differences can likely be attributed to physician preference or patient population. Obesity rates are elevated in rural areas. The implementation of MIS bariatric surgery programs in rural areas may improve the treatment of obesity and downstream co-morbidities in these populations. PMID- 26363718 TI - Comment on: Quality and safety in obesity surgery-15 years of Roux-en-Y gastric bypass outcomes from a longitudinal database. PMID- 26363719 TI - Sweet potato cysteine proteases SPAE and SPCP2 participate in sporamin degradation during storage root sprouting. AB - Sweet potato sporamins are trypsin inhibitors and exhibit strong resistance to digestion by pepsin, trypsin and chymotrypsin. In addition, they constitute the major storage proteins in the sweet potato and, after degradation, provide nitrogen as a nutrient for seedling regrowth in sprouting storage roots. In this report, four cysteine proteases-one asparaginyl endopeptidase (SPAE), two papain like cysteine proteases (SPCP1 and SPCP2), and one granulin-containing cysteine protease (SPCP3)-were studied to determine their association with sporamin degradation in sprouting storage roots. Sporamin degradation became significant in the flesh of storage roots starting from week 4 after sprouting and this correlated with expression levels of SPAE and SPCP2, but not of SPCP1 and SPCP3. In the outer flesh near the skin, sporamin degradation was more evident and occurred earlier than in the inner flesh of storage roots. Degradation of sporamins in the outer flesh was inversely correlated with the distance of the storage root from the sprout. Exogenous application of SPAE and SPCP2, but not SPCP3, fusion proteins to crude extracts of the outer flesh (i.e., extracted from a depth of 0.3cm and within 2cm of one-week-old sprouts) promoted in vitro sporamin degradation in a dose-dependent manner. Pre-treatment of SPAE and SPCP2 fusion proteins at 95 degrees C for 5min prior to their application to the crude extracts reduced sporamin degradation. These data show that sweet potato asparaginyl endopeptidase SPAE and papain-like cysteine protease SPCP2 participate in sporamin degradation during storage root sprouting. PMID- 26363720 TI - Recovery in bipolar depression: Post-hoc analysis of a placebo-controlled lurasidone trial followed by a long-term continuation study. AB - BACKGROUND: In this post-hoc analysis, rates of remission and recovery were evaluated in patients with bipolar depression treated with lurasidone. METHODS: Outpatients meeting DSM-IV-TR criteria for bipolar I depression, were randomized to 6 weeks of once-daily, double-blind treatment with lurasidone 20-60mg, lurasidone 80-120mg or placebo, followed by a 6-month, open-label, flexible-dose, lurasidone continuation study. Recovery was defined as meeting criteria for combined symptomatic remission (Montgomery-Asberg Depression Rating Scale total score <=12) and functional remission (all Sheehan Disability Scale domain scores <=3) sustained for at least 3 months in the 6-month continuation study. RESULTS: A significantly higher proportion of lurasidone-treated patients met criteria for combined symptomatic remission and functional remission (33.3%, 91/273) compared to the placebo group (21.0%, 30/143, p<0.05, NNT=9) at the 6-week study endpoint. In the 6-month continuation study, the proportion of lurasidone-treated patients achieving sustained recovery was 60.7% (85/140) and 44.9% (31/69), for patients who continued lurasidone treatment and who switched from placebo to lurasidone, respectively. LIMITATIONS: The definition of recovery used has not been previously validated and the analysis was post hoc. Lack of a control group in the continuation study limits data interpretation. CONCLUSIONS: Recovery in patients with bipolar depression was assessed based on rates of combined symptomatic and functional remission sustained over time. A majority of patients initially treated with lurasidone in the acute phase achieved recovery status in the continuation study. Treatment with lurasidone (vs. placebo) earlier in the course of the bipolar depressive episode increased the likelihood of subsequent recovery. PMID- 26363721 TI - Quality of life of older adults in rural southern Brazil. AB - INTRODUCTION: Ageing in rural communities poses unique challenges that can have an impact on older adults' quality of life (QoL). These limitations can be costly to the healthcare system but there is potential for them to be addressed with a better understanding of factors that affect QoL. The goal of this study was to assess the perceptions of QoL of older adults living in rural areas of southern Brazil and to identify factors associated with QoL in this population. METHODS: A cross-sectional study was conducted with 197 older adults (mean age 69.7+/-7.5 years). Instruments included the Katz and Lawton activities of daily living scales, QoL instruments and a questionnaire that addressed social, economic, demographic and health variables. Multiple regression analysis was performed, using various domains and overall QoL as dependent variables. RESULTS: Older adults who were more independent, living with a spouse, with higher income and educational levels, fewer morbidities, fewer years of tobacco use, and who did not report falls in the last year were significantly more likely to rate their QoL higher on one or more domains/measures. CONCLUSIONS: Factors associated with QoL of older adults in rural areas are similar to those found in studies conducted in urban areas, but the rural context may influence these variables in unique ways. PMID- 26363722 TI - Improving Quality of Cardiac Care: A Global Mandate. PMID- 26363723 TI - Five-year trends of selected halogenated flame retardants in the atmosphere of Northeast China. AB - This study collected 227 pairs of gas phase and particle phase air samples in a typical urban city of Northeast China from 2008 to 2013. Four alternative halogenated flame retardants for polybrominated diphenyl ethers (PBDEs) were analyzed, namely 2-ethylhexyl 2,3,4,5-tetrabromobenzoate (EHTBB), bis (2 ethylhexyl) tetrabromophthalate (BEHTBP), syn-dechlorane plus (syn-DP) and anti dechlorane plus (anti-DP). The average concentrations for EHTBB and BEHTBP were 5.2 +/- 20 and 30 +/- 200 pg/m3, respectively, while for syn-DP and anti-DPwere 1.9+/-5.1 and 5.8+/-18 pg/m3, respectively. Generally, they were frequently detected in the particle phase, and the gas/particle partitioning suggested they were the maximum partition chemicals. The fractional abundance of EHTBB (fEHTBB) and syn-DP (fsyn)were comparablewith those in other studies. Strong local sources were identified based on the air parcel backward trajectories and the potential source contribution function. The concentrations of these chemicals were significantly increased during this sampling campaign, possibly suggesting their increasing usages from 2008 to 2013 in China. PMID- 26363724 TI - Extended sorption partitioning models for pesticide leaching risk assessments: Can we improve upon the koc concept? AB - Models used to assess leaching of pesticides to groundwater still rely on the sorption koc value, even though its limitations have been known for several decades, especially for soils of low organic carbon content (i.e. subsoils). This is mainly because the general applicability of any improved model approach that is also simple enough to use for regulatory purposes has not been demonstrated. The objective of this study was to test and compare alternative models of sorption that could be useful in pesticide risk assessment and management. To this end, a database containing the results of batch sorption experiments for pesticides was compiled from published studies in the literature, which placed at least as much emphasis on measurements in subsoil horizons as in topsoil. The database includes 785 data entries from 34 different published studies and for 21 different active substances. Overall, the apparent koc value, koc(app), roughly doubled as the soil organic carbon content decreased by a factor of ten. Nevertheless, in nearly half of the individual datasets, a constant koc value proved to be an adequate model. Further analysis showed that significant increases in koc(app) in subsoil were found primarily for the more weakly adsorbing compounds (koc values=65years and varied according to geographic, longitudinal (0.07%; 95% CI: 0.05, 0.10), and climatic characteristics and the scale of DTR (0.33%; 95% CI: 0.12, 0.55) for overall all-cause mortality. The DTR is a risk factor affecting human health, depending on geographic location and the temperature variation, with particular vulnerability in aged populations. PMID- 26363727 TI - Mixing ratio and carbon isotopic composition investigation of atmospheric CO2 in Beijing, China. AB - The stable isotope composition of atmospheric CO2 can be used as a tracer in the study of urban carbon cycles, which are affected by anthropogenic and biogenic CO2 components. Continuous measurements of the mixing ratio and delta(13)C of atmospheric CO2 were conducted in Beijing from Nov. 15, 2012 to Mar. 8, 2014 including two heating seasons and a vegetative season. Both delta(13)C and the isotopic composition of source CO2 (delta(13)CS) were depleted in the heating seasons and enriched in the vegetative season. The diurnal variations in the CO2 mixing ratio and delta(13)C contained two peaks in the heating season, which are due to the effects of morning rush hour traffic. Seasonal and diurnal patterns of the CO2 mixing ratio and delta(13)C were affected by anthropogenic emissions and biogenic activity. Assuming that the primary CO2 sources at night (22:00-04:00) were coal and natural gas combustion during heating seasons I and II, an isotopic mass balance analysis indicated that coal combustion had average contributions of 83.83+/-14.11% and 86.84+/-12.27% and that natural gas had average contributions of 16.17+/-14.11% and 13.16+/-12.27%, respectively. The delta(13)C of background CO2 in air was the main error source in the isotopic mass balance model. Both the mixing ratio and delta(13)C of atmospheric CO2 had significant linear relationships with the air quality index (AQI) and can be used to indicate local air pollution conditions. Energy structure optimization, for example, reducing coal consumption, will improve the local air conditions in Beijing. PMID- 26363728 TI - Physical activity level and associated factors among civil servants in Xi'an, China. AB - OBJECTIVES: This study investigated physical activity levels and associated factors among civil servants in Xi'an, China, to provide reference data for the implementation of health improvement strategies among civil servants. DESIGN: A cross-section study. METHODS: A random sample of 1000 civil servants aged 18-60 years and employed by the Xi'an civic government was assessed by using the Chinese version of the International Physical Activity Questionnaire. Associations between physical activity and sociodemographic characteristics, family history of chronic disease, and existing disease were evaluated by the Mann-Whitney U-test, Kruskal-Wallis H-test, and binary logistic regression. RESULTS: The response rate was 92.4%. The median physical activity score was 2227 metabolic equivalents of task (MET) minutes per week (interquartile range [IQR]: 1308-3802METmin/week). Among the 924 participants, 7.4% did not meet minimum recommendations for physical activity, 57.3% had moderate activity levels, and 35.4% had high activity levels. Participants spent most of their time on occupational activities (median: 869METmin/week, IQR: 228-1953METmin/week). Female sex (odds ratio [OR]:0.40, 95% confidence interval [CI]:0.29-0.55), age>=51 years (OR: 0.45, 95%CI: 0.27-0.75), and family history of chronic disease (OR: 0.67, 95%CI: 0.48-0.94) were associated with significantly lower odds of a high activity level. CONCLUSIONS: Most civil servants in Xi'an, China, have moderate activity levels. Some have high activity levels, but few engage in vigorous-intensity physical activity. Interventions to encourage a high level of physical activity are needed, especially for women, older civil servants, and those with family histories of chronic disease. PMID- 26363729 TI - Synthesis, characterization and vibrational spectroscopic study of Co, Mg co doped LiMnPO4. AB - The isostructural olivine-like LiM(II)PO4 compounds [M(II)=Mn, Mn0.9Co0.1, Mn0.8Co0.1Mg0.1] were successfully generated through the solid state reaction from the synthesized NH4M(II)PO4?H2O precursors. The TG/DTG/DTA, AAS/AES, FTIR and XRD methods were employed to confirm both NH4M(II)PO4?H2O and LiM(II)PO4 compounds. Their morphologies were studied by SEM method. The shift of two theta angle of XRD to higher values was observed in metal doping compounds, which indicate the formation of the single phase of isodivalent doping of Co(2+) and Mg(2+) ions according to the change in the lattice parameters and cell volumes. Their infrared spectra are reported and discussed with respect to the normal vibrations of NH4(+), PO4(3-), P2O7(4-) and H2O molecules using factor group analysis. The correlation field splitting analysis of PO4(3-) in NH4M(II)PO4?H2O (orthorhombic system, Pmn2(1), C(2v)(7) and Z=2, [(3*5)-6]*2=18 internal modes) symbolized as T(d)-C(s)-C(2v)(7) suggested the number of vibrational modes to be: Gamma(Vib)=A1(6)+A2(3)+B1(6)+B2(3) and A1(6)+A2(3)+B1(3)+B2(6) for zx and yz plane respectively. While, LiM(II)PO4 crystallizes in the orthorhombic system the space group Pnma (D(2h)(16)), Z=4 and the site symmetry of PO4(3-) is C(s). The correlation field splitting of type T(d)-C(s)-D(2h)(16) were reported in relation to [(3*5)-6]*4=36 internal modes for PO4(3-) unit in the structure. PMID- 26363730 TI - Microwave-assisted Bi2Se3 nanoparticles using various organic solvents. AB - Microwave assisted Bi2Se3 nanoparticles were synthesized from five different solvents DMF, EG, EG+H2O, EDA+dil.HNO3 and N2H4+H2O+Ethanol. The influence of solvents on purity of the compound was analysed by using X-ray diffraction patterns. The result indicates pure rhombohedral Bi2Se3 nanoparticles formed for N2H4+H2O+Ethanol. The presence of vibrational bands in the range of 400-800 cm( 1) is confirmed the formation of Bi2Se3. The maximum optical absorption observed around 450 nm and the band gap values are found in the range of 1.5 eV-2.17 eV for all the solvents. The nanostructure of the Bi2Se3 particles change with solvents. From the experimental results, the solvent N2H4+H2O+Ethanol produces pure nanosize Bi2Se3 particles under the microwave assisted method. PMID- 26363731 TI - Selective interactions of trivalent cations Fe3+, Al3+ and Cr3+ turn on fluorescence in a naphthalimide based single molecular probe. AB - Synthesis and fluorescence turn-on behavior of a naphthalimide based probe is described. Selective interactions of trivalent cations Fe(3+), Al(3+) or Cr(3+) with probe 1 inhibit the PET operating in the probe, and thereby, permit the detection of these trivalent cations present in aqueous samples and live cells. Failure of other trivalent cations (Eu(3+), Gd(3+) and Nb(3+)) to inhibit the PET process in 1 demonstrates the role of chelating ring size vis-a-vis ionic radius in the selective recognition of specific metal ions. PMID- 26363732 TI - Relationship between knee adduction moment patterns extracted using principal component analysis and discrete measures with different amplitude normalizations: Implications for knee osteoarthritis progression studies. AB - BACKGROUND: Knee adduction moment discrete features (peaks and impulses) are commonly reported in knee osteoarthritis gait studies, but they do not necessarily capture loading patterns. Principal component analysis extracts dynamic patterns, but can be difficult to interpret. This methodological study determined relationships between external knee adduction moment discrete measures and principal component analysis features, and examined whether amplitude normalization methods influenced differences in those with knee osteoarthritis who progressed to surgery versus those that did not. METHODS: 54 knee osteoarthritis patients had three-dimensional biomechanical measures assessed during walking. Knee adduction moments were calculated and non-normalized and amplitude-normalized waveforms using two common methods were calculated. Patterns were extracted using principal component analysis. Knee adduction moment peak and impulse were calculated. Correlation coefficients were determined between two knee adduction moment patterns extracted and peak and impulse. T-tests evaluated between-group differences. FINDINGS: An overall magnitude pattern was correlated with peak (r=0.88-0.90, p<0.05) and impulse (r=0.93, p<0.05). A pattern capturing a difference between early and mid/late -stance knee adduction moment was significantly correlated with peak (r=0.27-0.40, p<0.05), but explained minimal variance. Between-group peak differences were only affected by amplitude normalization method. INTERPRETATION: Findings suggest that the overall magnitude knee adduction moment principal pattern does not provide unique information from peak and impulse measures. However, low correlations and minimal variance explained between the pattern capturing ability to unload the joint during mid stance and the two discrete measures, suggests that this pattern captured a unique waveform feature. PMID- 26363733 TI - Developmental changes in the expression and function of TRPC6 channels related the F-actin organization during differentiation in podocytes. AB - The transient receptor potential canonical (TRPC) 6 channel is an important ion channel located in podocytes, which plays an essential role in regulating calcium homeostasis of the cell signaling. Podocytes are specialized, terminally differentiated cells surrounding glomerular capillaries, and are the subject of keen interest because of their key roles in kidney development and disease. Here we wonder whether TRPC6 channels undergo developmental changes in the expression and function during the podocyte differentiation, and whether they contribute to the maturation of podocytes. Using morphological, immunohistochemical and electrophysiological techniques, we investigated the development of distribution and expression of TRPC6 in conditionally immortalized mouse podocyte cell line. Our results showed that the distribution of TRPC6 channels changed with the maturity of podocyte differentiation. The fluorescent intensity of TRPC6 on cell surface increased, which was accompanied by a corresponding increase in the density of current flowing through the channels. TRPC6 inhibition by TRPC6 siRNA or SKF-96365, a blocker or TRP cation channels, resulted in F-actin cytoskeleton disruption only on the developmental stage of podocytes. These results strongly support the conclusion that TPRC6 is an essential component of the slit diaphragm and is required for development of glomerulus. PMID- 26363734 TI - Respiratory management of patients with Fukuyama congenital muscular dystrophy. AB - BACKGROUND: Fukuyama congenital muscular dystrophy (FCMD), characterized by intellectual impairment associated with cortical migration defects, is an autosomal recessive disorder caused by mutation in the fukutin gene. It is the second most common type of muscular dystrophy in Japan. Respiratory dysfunction, along with cardiomyopathy, can be life-threatening in patients with advanced stage FCMD. However, few reports have focused on this issue. METHODS: We retrospectively studied respiratory dysfunction and therapeutic management in 48 genetically diagnosed FCMD patients (mean age 11.0 years; range 3.6-31.9 years). RESULTS: Mechanical ventilation was initiated at a median age of 12.1 years in 16 patients, 14 of whom received non-invasive positive pressure ventilation (NPPV) while the other 2 underwent tracheostomy with invasive ventilation (TIV). The two TIV cases had unexpectedly required the initiation of ventilatory support at the ages of 15.7 and 18.0 years, respectively, because of unsuccessful extubation followed by serious respiratory infections, despite rather good respiratory function before these episodes. Patients carrying a compound heterozygous founder mutation or with a severe phenotype tended to need ventilatory support 2-3 years earlier than homozygous patients and those with the typical or mild phenotype. Mechanical insufflation-exsufflation (MI-E) interventions were also employed in six patients with serious dysphagia and were well-tolerated in all cases. CONCLUSION: For respiratory management, it is important to regularly evaluate respiratory function in FCMD patients over 10 years of age, since intellectual impairment and insomnia often mask the signs of respiratory dysfunction. Most patients, despite poor cooperation due to intellectual impairment, can tolerate NPPV and MI-E provided that a carefully worked-out plan is adopted. PMID- 26363735 TI - The relationship between sperm quality in cool-shipped semen and embryo recovery rate in horses. AB - The relationship between the quality of cool-shipped stallion semen and fertility has not been adequately described. This study evaluated sperm quality of cool shipped semen from 459 ejaculates (N = 130 stallions) that were used for insemination of 196 embryo donor mares (n = 496 estrous cycles). Embryo recovery rate (ERR; %) increased, as all sperm measures (e.g., motility, viability, DNA quality, morphology, concentration, and total number) increased. Threshold values are reported for each sperm quality measure (e.g., total sperm motility >= 65%) that separate two ERR groups (e.g., average: ~50% ERR; high: ~65% ERR). PMID- 26363736 TI - Oscillating Transcriptome during Rice-Magnaporthe Interaction. AB - Rice blast disease caused by the fungus, Magnaporthe oryzae, is one of the most devastating diseases of rice. Deciphering molecular mechanism of host-pathogen interactions is of great importance in devising disease management strategies. Transcription being the first step for gene regulation in eukaryotes, basic understanding of the transcriptome is sine qua non for devising effective management strategy. The availability of genome sequences of rice and M. oryzae has facilitated the process to a large extent. The current review summarizes recent understanding of rice-blast pathosystem, application of transcriptomics approaches to understand the interactions employing different platforms, major determinants in the interaction and possibility of using certain candidate for conditioning enhanced disease resistance (Effector Triggered Immunity and PAMP Triggered Immunity) and downstream signalling in rice. A better understanding of the interaction elements and effective strategies hold potential to reduce yield losses in rice caused by M. oryzae. PMID- 26363737 TI - Reducing maternal mortality on a countrywide scale: The role of emergency obstetric training. AB - Training programmes to improve health worker skills in managing obstetric emergencies have been introduced in various countries with the aim of reducing maternal mortality through these interventions. In South Africa, based on an ongoing confidential enquiry system started in 1997, detailed information about maternal deaths is published in the form of regular 'Saving Mothers' reports. This article tracks the recommendations made in successive Saving Mothers reports with regard to emergency obstetric training, and it assesses the impact of these recommendations on reducing maternal mortality. Since 2009, South Africa has had its own training package, Essential Steps in the Management of Obstetric Emergencies (ESMOE), which the last three Saving Mothers reports have specifically recommended for all doctors and midwives working in maternity units. A special emphasis has been placed on the need for the simulation training component of ESMOE, also called obstetric 'fire drills', to be integrated into the clinical routines of all maternity units. The latest Saving Mothers report (2011-2013) suggests there has been little progress so far in improving emergency obstetric skills, indicating a need for further scale-up of ESMOE training in the country. The example of the KwaZulu-Natal province of South Africa is used to illustrate the process of scale-up and factors likely to facilitate that scale up, including the introduction of ESMOE into the undergraduate medical training curriculum. Additional factors in the health system that are required to convert improved skills levels into improved quality of care and a reduction in maternal mortality are discussed. These include intelligent government health policies, formulated with input from clinical experts; strong clinical leadership to ensure that doctors and nurses apply the skills they have learnt appropriately, and work professionally and ethically; and a culture of clinical governance. PMID- 26363741 TI - Depression is a systemic disease. PMID- 26363742 TI - Major depressive disorder in chronic heart failure patients: Does silent cerebral infarction cause major depressive disorder in this patient population? AB - OBJECTIVE: Depression frequently occurs in patients with heart failure as similar pathophysiological mechanisms present in both these diseases. Patients with dilated cardiomyopathy (DCM) have a high incidence of clinically asymptomatic silent cerebral infarction (SCI). This study aimed to evaluate the relation between SCI and major depressive disorder (MDD), and between MDD and clinical and biochemical parameters in DCM patients. METHODS: Patients with ischemic and non ischemic DCM who had chronic heart failure (CHF) (39 male, 10 female, age 60+/-10 years) were included in the study. Mean patient ejection fraction (EF) was 34+/ 10%. Patients had no localized neurological symptoms or stroke history. The etiology of DCM was ischemic in 40 and non-ischemic in 9 patients. Twenty-five age-matched healthy volunteers served as a control group for comparison of SCI and MDD prevalence. RESULTS: Patients had mild to severe CHF symptoms. Prevalence of SCI and MDD was significantly higher in patients with DCM than in the control group; 63% vs 8%; p<0.001, and 52% vs 20%; p<0.001 respectively. Patients with SCI had a higher prevalence of MDD than patients without SCI in DCM (61% vs 27%, p=0.02). CONCLUSION: CHF patients have an increased prevalence of SCI and MDD. Patients with SCI have a higher prevalence of MDD compared to patients without SCI in CHF. PMID- 26363743 TI - Determinants of iatrogenic femoral pseudoaneurysm after cardiac catheterization or percutaneous coronary intervention via the femoral artery. AB - OBJECTIVE: This study aimed to define the prevalence and predictors for pseudoaneurysm after coronary angiography, cardiac catheterization and percutaneous coronary interventions (PCIs) performed via the femoral artery. METHODS: The study included 8469 patients enrolled between January 2007 and December 2009 on whom cardiac catheterization, coronary and/or peripheral angiography and PCIs via the femoral artery were performed. All data, including clinical characteristics and complications, were obtained retrospectively from patient chart records. RESULTS: Pseudoaneurysm was detected in 65 (0.76%) patients. Pseudoaneurysm was ascertained more frequently in patients with a history of coronary artery disease (0.9% vs. 0.4%; p=0.012), in females than in males (1.4% vs. 0.5%; p<0.001), in patients older than 65 years (1.2% vs. 0.6%; p=0.002), in patients with a history of femoral artery intervention (1.2% vs. 0.6%; p=0.01), in hypertensives than in normotensives (1.3% vs. 0.5%; p<0.001), in patients taking low molecular weight heparin (1.0% vs. 0.2%; p<0.001), in patients taking clopidogrel (1.0% vs. 0.4%; p=0.007), and in patients with chronic renal disease (3.8% vs. 0.7%; p<0.001). There was no statistically significant trend (1.2% vs. 0.7%; p=0.053) towards more pseudoaneurysm formation in emergent interventions than in elective procedures. CONCLUSION: Patients with a higher risk of pseudoaneurysm development following intervention via the femoral artery should be specified and extra attention given during the intervention. These patients should be informed of the increased risk of this complication and its results, and should be under close follow-up concerning development of iatrogenic femoral pseudoaneurysm. PMID- 26363744 TI - The prognostic value of a prominent Q wave in lead (-)aVR in acute anterior wall myocardial infarction. AB - OBJECTIVE: This study aimed to determine the association of a prominent Q wave in lead (-)aVR with clinical, echocardiographic and angiographic findings in anterior ST elevation myocardial infarction (STEMI) and to evaluate the role of this finding in short-term and long-term outcomes. METHODS: During a one-year period, 150 patients with first time anterior STEMI were screened and 121 patients with no other cardiopulmonary and renal comorbid diagnoses were included in the study. Patients were allocated into two groups based on presence or absence of a prominent Q wave in lead (-)aVR. All clinical, electrocardiographic, echocardiographic and angiographic data were recorded and compared between the groups. In-hospital adverse outcomes and mortality as well as two-year survival were also compared. RESULTS: Among 121 patients (mean age: 62.8+/-12.5 years) 26.4% had a prominent Q wave in lead (-)aVR. The prevalence of multi-vessel disease was higher in patients with a Q wave (76.9% vs. 52.8%, p=0.03). ST segment elevation in lead V6 was significantly more common in those with a Q wave (50% vs. 30.3%, p=0.04). Posterobasal region motion abnormality was more common in the Q wave group. (9.4% vs. 1.2% respectively, p=0.04). Overall, mortality was higher in the Q wave group; however, it was not statistically significant (15.4% vs. 9.3%, p=0.39). CONCLUSION: In anterior STEMI, presence of a Q wave in lead ( )aVR is associated with occlusion of multiple arteries. Short- and mid-term mortality are not affected by this ECG finding. PMID- 26363745 TI - Transcatheter aortic valve implantation in the presence of hematologic malignancies. AB - OBJECTIVE: Cardiac surgery may be performed in patients with hematologic disorders, but carries an increased risk of morbidity. This series describes an experience of transcatheter aortic valve implantation (TAVI) in patients with hematologic malignancies, and highlights the technical considerations to be kept in mind. METHODS: Between June 2011 and April 2014, 133 consecutive high-risk patients with symptomatic severe aortic stenosis were treated with TAVI at our centre. Based on consensus among the local heart team, five patients with hematologic malignancies (myelodysplastic syndrome [2],chronic lymphocytic leukemia [2], Hodgkin lymphoma [1]) were considered high risk for surgery (Logistic EUROSCORE 17.2+/-14.0% and STS score 5.8+/-4.3%). Serial echocardiographic and clinical follow-ups were done pre- and post-procedure, at discharge, and at 1, 3, 6 and 12 months. RESULTS: Our procedural success rate was 80%. Two heart valves were implanted in one patient due to aortic embolization of the previous valve. Perforation of the right ventricle and cardiac tamponade occurred in the same patient. Mean blood transfusion requirement was 1.0+/-1.4 U (range: 0 to 3 U). Mean aortic valve gradient was reduced from baseline to 9.2+/ 3.27 mmHg, and the effective orifice area was significantly increased to 1.96+/ 0.29 cm2. Paravalvular aortic regurgitation (AR) was absent-mild in all the patients. CONCLUSION: This present series demonstrates that TAVI with a balloon expandable valve can be performed safely and effectively and is technically feasible in high-risk patients with hematologic malignancies. PMID- 26363746 TI - Evaluation of depression and anxiety in parents of children undergoing cardiac catheterization. AB - OBJECTIVE: This study aimed to determine pre-procedure depression and anxiety levels among a group of parents whose children had congenital heart disease and were undergoing angiography. METHODS: The study comprised parents of 73 congenital heart disease patients undergoing angiography. The Beck Depression Inventory (BDI) and the Beck Anxiety Inventory (BAI) were used to evaluate the depression and anxiety scores. RESULTS: Sixty-one patients (83.6%) had acyanotic congenital heart disease, and 25 patients (34.2%) were undergoing diagnostic angiography. BDI scores among the mothers determined that 8 (11%) had mild, 14 (19.2%) moderate, and 10 (13.7%) severe depression. Their BAI scores showed that 16 (21.9%) had mild, 8 (11%) moderate, and 13 (17.8%) severe anxiety. BDI scores for the fathers showed that 12 (16.4%) had mild, 10 (13.7%) moderate, and 8 (11%) severe depression. Their BAI scores showed that 12 (16.4%) had mild, 10 (13.7%) moderate, and 8 (11%) severe anxiety. A comparison of mothers of cyanotic patients and those of acyanotic patients in terms of depression and anxiety levels revealed a statistically significant difference (p=0.050 and 0.043, respectively). CONCLUSION: Angiography was associated with increased levels of depression and anxiety in parents of children with congenital heart diseases. In comparison to parents of patients with acyanotic congenital heart disease, mothers of patients with cyanotic congenital heart disease had significantly higher levels of depression and anxiety. PMID- 26363747 TI - Pulmonary and ventricular functions in children with repaired tetralogy of Fallot. AB - OBJECTIVE: This study aimed to evaluate biventricular function, brain natriuretic peptide levels, respiratory function test and 6 minute walking test (6MWT) in children with repaired tetralogy of Fallot (TOF), and analyse the correlation between these variables and clinical status. METHODS: Twenty-five children (14 boys, 11 girls; aged 6 to 17 years) with repaired TOF (Group 1) and 25 age-sex matched healthy controls (Group 2) were enrolled in the study. Tissue Doppler echocardiography, respiratory function test, 6MWT distance and brain natriuretic peptide levels were measured. RESULTS: Mean ages of the children at TOF corrective surgery and at study time were 5.1+/-3.5 years and 11.6+/-2.7 years respectively. The duration between palliative operation and corrective surgery was 4.3+/-2.0 years, and the follow-up period after corrective surgery was 6.3+/ 3.0 years. The right ventricular and left ventricular myocardial performance indices (MPIs), and isovolumic relaxation and contraction times were significantly higher in Group 1 than in Group 2 (p<0.01). Spirometry displayed significantly reduced forced vital capacity (FVC), forced expiratory volume in one second (FEV1), forced expiratory flow 25-75% (FEF25-75) and inspirational capacity in Group 1 compared to Group 2 (p<0.01). In Group 1, 6MWT distances were significantly lower than in Group 2 (p=0.001). Right ventricular MPI is correlated with FEV1, FVC and 6MWT distance in the current study. CONCLUSION: The children with repaired TOF had impaired ventricular and pulmonary functions. Hence, right ventricular MPI along with FEV1, FVC and 6MWT distance may be useful in the follow-up of children with repaired TOF. PMID- 26363749 TI - An unusual thrombolytic therapy decision in prosthetic valve thrombosis during early pregnancy. AB - Pregnancy is among the risk factors for mechanical valve thrombosis, and even though thrombolytic therapy is contraindicated during pregnancy, it may be used in the treatment of this life-threatening complication. This case report describes a pregnant patient, whose echocardiogram showed evident gradient increase on her mechanical prosthetic mitral valve, and who was treated successfully with tissue plasminogen activator for mechanical valve thrombosis. PMID- 26363748 TI - A rare coronary anomaly with masked diagnosis: Anomalous left circumflex artery from right pulmonary artery. AB - Anomalous origin of the circumflex coronary artery from the pulmonary artery is a rare congenital coronary anomaly. While it generally follows an asymptomatic course, if undiagnosed it may lead to severe clinical outcomes, including sudden death. The condition can be masked by associated defects, so when it is clinically suspected, diagnosis must be confirmed by conventional and/or magnetic resonance angiography, even if echocardiography clearly shows coronary roots. This report describes a patient who underwent neonatal surgery for aortic coarctation and was diagnosed with coronary artery anomaly at 15 months old. PMID- 26363750 TI - Acute coronary syndrome due to midazolam use: Kounis syndrome during a transurethral prostatectomy. AB - Developments in the drugs industry are leading to more rare drug side effects being encountered in clinical practice. Of these side effects, allergic reactions and hypersensitivity are seen in the usage of a large group of drugs such as antibiotics, analgesics, antineoplastics, contrast agents, corticosteroids, intravenous anesthetics, nonsteroidal anti-inflammatory drugs, and proton pump inhibitors. One important result of these reactions is acute coronary syndrome, which may have serious life-threatening results. This syndrome was first described in 1991 by Kounis as an 'allergic angina syndrome progressing to acute myocardial infarction', and thereafter called 'allergic myocardial infarction'. This case report presents a 70-year-old male who had angina and dyspnea after administration of midazolam at the beginning of a transurethral prostatectomy operation. PMID- 26363751 TI - Percutaneous transcatheter closure of a descending aorta to vertebral venous plexus fistula using an Amplatzer Vascular Plug 2: a case report. AB - A descending aorta to vertebral venous plexus fistula is an extremely rare form of arteriovenous fistula. A 10-month-old infant was referred to the hospital for evaluation of a murmur. On examination, a continuous murmur was heard in the entire back. Transthoracic echocardiography revealed left heart chamber dilatation in the presence of preserved left ventricle systolic function. Computerized tomography angiography with 3-dimensional reconstruction, and lateral projection aortography revealed a descending aorta-vertebral venous plexus fistula measuring 4.8 mm in the aortic orifice. The fistula was embolized using an Amplatzer Vascular Plug 2. PMID- 26363752 TI - Non-surgical treatment of a right ventricle puncture during diagnostic pericardiocentesis. AB - Pericardiocentesis is a life-saving procedure performed in cardiac tamponade cases occurring in infective, inflammatory or malignancy conditions, or following percutaneous coronary intervention, cardiac device implantation or catheter ablation. In spite of advanced imaging methods, a substantial risk of complication persists. Emergent surgical intervention may be required, in particular during advancement of the catheter into the heart chambers or in cases of wall rupture. Furthermore, in all these cases, patients have a high risk of surgery because of existing comorbidities. This case presents a patient suspected of tuberculous pericarditis who underwent diagnostic pericardiocentesis complicated by right ventricular puncture. The catheter in the right ventricle was withdrawn via a second catheter placed in the pericardial cavity. Spontaneous blood control was established, and with no increase in pericardial effusion surgical intervention was not required. This method can be applied in certain conditions, including cardiac injury caused by pericardiocentesis or intracardiac manipulations, thus eliminating the need for high-risk surgical intervention. PMID- 26363753 TI - Catheter ablation of ventricular arrhythmia originating in the tricuspid annulus in a patient with biventricular noncompaction: a case report. AB - It is rare for ventricular tachycardia arising from the right ventricle to originate in the tricuspid annulus, and the clinical presentation and cardiac abnormalities associated with this type of arrhythmia have not been clearly established. This report describes a case of biventricular noncompaction presenting with ventricular arrhythmia originating in the tricuspid annulus and successfully treated with radiofrequency ablation. PMID- 26363754 TI - How to perform an endomyocardial biopsy? PMID- 26363755 TI - A case of Gerbode-type ventricular septal defect and mitral anterior valve cleft with severe regurgitation. PMID- 26363756 TI - Concomitant presence of blood cyst and atrial septal defect: A rare association. PMID- 26363757 TI - An unusual cause of syncope: Mitral valve myxoma. PMID- 26363758 TI - Common atrium: A rare congenital heart anomaly. PMID- 26363759 TI - One sinus, three arteries: An unexpected coronary anomaly. PMID- 26363760 TI - Where do we stand in occupational cardiology? PMID- 26363761 TI - An elderly patient with atresia of the left main stem. PMID- 26363762 TI - Authors' reply. PMID- 26363763 TI - Is balloon sizing still necessary in the era of real-time 3D transesophageal echocardiography? PMID- 26363764 TI - Does occupation refer to an advantage or obstacle before transradial cardiac catheterization? PMID- 26363765 TI - Left ventricular hypertrabeculation/noncompaction in hyperoxaluria. PMID- 26363766 TI - Authors' reply. PMID- 26363767 TI - Escherichia coli O157:H7 reduction in hamburgers with regard to premature browning of minced beef, colour score and method for determining doneness. AB - This study investigated the effect of premature browning (PMB) on the survival of Escherichia coli O157:H7 in beef hamburgers after cooking with respect to interior colour of the hamburger and recommendations to cook hamburgers to a core temperature of 71 degrees C. Assessment of doneness by visual inspection or measurement of internal temperature was compared in terms of survival and the increased relative risk of illness due to PMB was estimated. At the last consume by-day, hamburgers made from minced meat packaged in 80/20 O2/CO2 (MAP hamburger) and from meat minced at retail packaged in atmospheric condition (control hamburger) were inoculated with a gfp-tagged strain of E. coli O157:H7 (E. coli O157:H7gfp+). Hamburgers were cooked for different times during assessment of the core temperature every 30s and cut in halves after cooking. Doneness was evaluated based on visual judgement of the internal colour using a score chart (C score) from 'uncooked' (score 1) to 'tan with no evidence of pink' (score 5). An alternative five point score chart (TCC-score) including texture of the meat, clarity of meat juice and internal colour was also developed. Enumeration of viable E. coli O157:H7gfp+ in cooked hamburgers was based on fluorescent colonies recovered from plates. Results showed that MAP hamburgers developed PMB when compared with controls (P=0.0003) and that the shortest cooking time for the highest C-score was 6 and 11 min for MAP and control hamburgers, respectively. The mean temperature in the MAP hamburger was then 60.3 degrees C. The TCC-score reduced the difference between MAP and control hamburgers. It was also shown that the survival of E. coli O157:H7gfp+ was highest in MAP hamburgers. The predicted absolute risks for illness were highest for MAP hamburgers for all C-scores and the relative risk associated with PMB increased with doneness. For a C-score of 4 (slightly pink) the predicted relative risk for illness was 300 times higher for MAP hamburger than for controls. A variable pathogen reduction was observed when cooking hamburgers to temperatures of 70-76 degrees C (the 5th and 95th percentile range was around 3.3 log CFU). The lower reductions, at the 5th percentile, may, depending on initial contamination levels, not be enough to ensure sufficient and safe inactivation of E. coli O157:H7. Efforts to inform consumers about PMB in minced meat packaged in high oxygen packages (>=60% O2) are needed with the aim to make consumers use thermometers correctly or at least not determine doneness based only on meat colour. PMID- 26363768 TI - Medical innovation laws: an unnecessary innovation. AB - Objective This paper aims to demonstrate that any suggestion that there is a need for specific innovation laws is flawed. Innovation is central to good medical practice and is adequately supported by current law. Methods The paper reviews the nature of medical innovation and outlines recent attempts in the UK to introduce specific laws aimed at 'encouraging' and 'supporting' innovation. The current legal framework is outlined and the role of the law in relation to medical innovation explored. Results The analysis demonstrates the cyclic relationship between medical advancement and the law and concludes that there is no requirement for specific innovation laws. Conclusions The law not only supports innovation and development in medical treatment but encourages it as central to a functioning medical system. There is no need to introduce specific laws aimed at medical innovation; to do so represents an unnecessary legal innovation and serves to complicate matters. What is known about the topic? Over recent months, there has been a great deal of discussion surrounding the law in the context of medical innovation. This was driven by the attempts in the UK to introduce specific laws in the Medical Innovation Bill. The general subject matter - negligence and the expected standard of care in the provision of treatment - is very well understood, but not in cases where the treatment can be described as innovative. The general rhetoric in both the UK and Australia around the Medical Innovation Bill demonstrates a lack of understanding of the position of the law with regards to innovative treatment. What does this paper add? This paper adds clarity to the debate. It presents the law and explains the manner in which the law can operate around innovative treatment. The paper asserts that medical innovation is both supported and encouraged by existing legal principles. What are the implications for practitioners? The paper presents an argument that can guide the policy position in this area. It also provides clarity around the legal position and expected standard of care for those who are introducing innovative medical treatment. PMID- 26363769 TI - Causal mediation analysis with a latent mediator. AB - Health researchers are often interested in assessing the direct effect of a treatment or exposure on an outcome variable, as well as its indirect (or mediation) effect through an intermediate variable (or mediator). For an outcome following a nonlinear model, the mediation formula may be used to estimate causally interpretable mediation effects. This method, like others, assumes that the mediator is observed. However, as is common in structural equations modeling, we may wish to consider a latent (unobserved) mediator. We follow a potential outcomes framework and assume a generalized structural equations model (GSEM). We provide maximum-likelihood estimation of GSEM parameters using an approximate Monte Carlo EM algorithm, coupled with a mediation formula approach to estimate natural direct and indirect effects. The method relies on an untestable sequential ignorability assumption; we assess robustness to this assumption by adapting a recently proposed method for sensitivity analysis. Simulation studies show good properties of the proposed estimators in plausible scenarios. Our method is applied to a study of the effect of mother education on occurrence of adolescent dental caries, in which we examine possible mediation through latent oral health behavior. PMID- 26363770 TI - Red wine is more than just an alcoholic beverage. PMID- 26363771 TI - Position statement of the SEMI, SED, redGDPS, SEC, SEEDO, SEEN, SEMERGEN y SEMFYC. AB - Obesity and excess weight are the main preventable causes of type 2 diabetes (DM2). When diagnosing type 2 diabetes, clinicians should establish the degree of obesity according to the body mass index (BMI) and, for patients with excess weight, measure the waist circumference. The proper treatment of DM2 requires a simultaneous approach to excess weight/obesity and the other cardiovascular risk factors, such as hypertension, dyslipidaemia and smoking. Nondrug interventions (e.g., diet and exercise) have proven benefits in preventing and treating patients with DM2 and excess weight/obesity and should follow an individual and multidisciplinary approach, with structured programs equipped with specific resources. Weight gain associated with antidiabetic treatment can hinder glycaemic control, compromise treatment adherence, worsen the vascular risk profile and limit the cardiovascular benefits of treatment. Therefore, it is significant to avoid weight gain, a measure that can be cost-effective. Antidiabetic drugs with benefits in body weight have also demonstrated their benefit in patients with BMIs <30. In general, the treatment of patients with DM2 and obesity will depend both on the degree of obesity and the associated comorbidity. Clinical trials on DM2 intervention should consider combined objectives that include not only glycaemic control but also other variables such as the risk of hypoglycaemia and the effect of treatment on body weight. PMID- 26363772 TI - Maternal Stress in Gestation: Birth Outcomes and Stress-Related Hormone Response of the Neonates. AB - BACKGROUND: Relatively few studies have been made on neurobehavioral outcomes of prenatal maternal stress during the newborn period, and little research has focused on umbilical cord stress hormones including cortisol, adrenocorticotropic hormone (ACTH), norepinephrine, and epinephrine. Our objective was to investigate the effects of prenatal maternal life stressors on neonatal birth outcomes, neurobehavioral development, and stress-related hormones levels. METHODS: Participants were 142 mothers and their infants; 71 were selected as the prenatal life stressor exposed group and 71 as the control group matched on maternal age, gestational week, delivery type, socioeconomic and education status, and newborns' sex. Maternal life stressors during pregnancy were determined using the Life Events Scale for Pregnant Women. Neonatal neurobehavioral development was assessed with the Neonatal Behavioral Neurological Assessment. Umbilical cord plasma stress-related hormones, including ACTH, cortisol, norepinephrine, and epinephrine were measured using an enzyme-linked immunosorbent assay. RESULTS: In the prenatal life stressors exposed group, newborns had significantly lower birth weight, smaller head circumference (p < 0.01, p < 0.01, respectively). Scores of Neonatal Behavioral Neurological Assessment were significantly reduced (p < 0.001). Cord plasma ACTH, norepinephrine, and epinephrine levels were significantly increased (p < 0.001), but cortisol levels were reduced (p < 0.001). CONCLUSION: Prenatal maternal stress may negatively affect fetal birth outcomes, neurobehavioral development and affect neonates' cord plasma ACTH, cortisol, norepinephrine, and epinephrine. PMID- 26363773 TI - Author's response. PMID- 26363774 TI - Reviewer's response. PMID- 26363775 TI - New methods for treatment effect calibration, with applications to non inferiority trials. AB - In comparative effectiveness research, it is often of interest to calibrate treatment effect estimates from a clinical trial to a target population that differs from the study population. One important application is an indirect comparison of a new treatment with a placebo control on the basis of two separate randomized clinical trials: a non-inferiority trial comparing the new treatment with an active control and a historical trial comparing the active control with placebo. The available methods for treatment effect calibration include an outcome regression (OR) method based on a regression model for the outcome and a weighting method based on a propensity score (PS) model. This article proposes new methods for treatment effect calibration: one based on a conditional effect (CE) model and two doubly robust (DR) methods. The first DR method involves a PS model and an OR model, is asymptotically valid if either model is correct, and attains the semiparametric information bound if both models are correct. The second DR method involves a PS model, a CE model, and possibly an OR model, is asymptotically valid under the union of the PS and CE models, and attains the semiparametric information bound if all three models are correct. The various methods are compared in a simulation study and applied to recent clinical trials for treating human immunodeficiency virus infection. PMID- 26363776 TI - Sensitivity of glomalin-related soil protein to wildfires: Immediate and medium term changes. AB - Forest fires are part of many ecosystems, especially in the Mediterranean Basin. Depending on the fire severity, they can be a great disturbance, so it is of special importance to know their impact on the ecosystem elements. In this study, we measured the sensitivity of glomalin related soil protein (GRSP), a glycoprotein produced by arbuscular mycorrhizal fungi (AMF), to fire perturbation. Two wildfire-affected areas in the SE Spain (Gata and Gorga) were studied. Soil organic carbon (SOC) was also measured. Effects on GRSP immediately after fire were analyzed in both areas, while in Gorga a monitoring of GRSP stocks over a year period after the fire was also carried out. Soil samplings were carried out every 4months. Plots (1*2m2) were installed beneath pines and shrubs in burned and an adjacent control area. Results of GRSP content immediately after a fire only showed significant differences for shrub plots (burned vs control) (p<0.01) in the Gorga site. However, a year of monitoring showed significant fire effect on GRSP content in both plot types (pines and shrubs). Control plots varied considerably over time, while in burned plots GRSP content remained constant during the whole studied period. This research provides evidence of the sensitivity of GRSP to a wildfire perturbation. PMID- 26363777 TI - Limbic correlates of fearlessness and disinhibition in incarcerated youth: Exploring the brain-behavior relationship with the Hare Psychopathy Checklist: Youth Version. AB - The purpose of this study was to determine whether scores on two temperament dimensions (fearlessness and disinhibition) correlated differentially with gray matter volumes in two limbic regions (amygdala and hippocampus). It was predicted that the fearlessness dimension would correlate with low gray matter volumes in the amygdala and the disinhibition dimension would correlate with low gray matter volumes in the hippocampus after controlling for age, IQ, regular substance use, and total brain volume. Participants were 191 male adolescents (age range=13-19 years) incarcerated in a maximum-security juvenile facility. Structural magnetic resonance imaging (MRI) analysis of the limbic and paralimbic regions of the brain was conducted. The temperament dimensions were estimated with items from the Psychopathy Checklist: Youth Version (PCL: YV: Forth et al., 2003). Analyses showed that the fearlessness dimension correlated negatively with gray matter volumes in the amygdala and the disinhibition dimension correlated negatively with gray matter volumes in the hippocampus but not vice versa. These findings provide preliminary support for the construct validity of the fearlessness and disinhibition temperament dimensions and offer confirmatory evidence for involvement of the amygdala and hippocampus in fear conditioning and behavioral inhibition, respectively. PMID- 26363778 TI - Paper membrane-based SERS platform for the determination of glucose in blood samples. AB - In this report, we present a paper membrane-based surface-enhanced Raman scattering (SERS) platform for the determination of blood glucose level using a nitrocellulose membrane as substrate paper, and the microfluidic channel was simply constructed by wax-printing method. The rod-shaped gold nanorod particles were modified with 4-mercaptophenylboronic acid (4-MBA) and 1-decanethiol (1-DT) molecules and used as embedded SERS probe for paper-based microfluidics. The SERS measurement area was simply constructed by dropping gold nanoparticles on nitrocellulose membrane, and the blood sample was dropped on the membrane hydrophilic channel. While the blood cells and proteins were held on nitrocellulose membrane, glucose molecules were moved through the channel toward the SERS measurement area. Scanning electron microscopy (SEM) was used to confirm the effective separation of blood matrix, and total analysis is completed in 5 min. In SERS measurements, the intensity of the band at 1070 cm(-1) which is attributed to B-OH vibration decreased depending on the rise in glucose concentration in the blood sample. The glucose concentration was found to be 5.43 +/- 0.51 mM in the reference blood sample by using a calibration equation, and the certified value for glucose was 6.17 +/- 0.11 mM. The recovery of the glucose in the reference blood sample was about 88 %. According to these results, the developed paper-based microfluidic SERS platform has been found to be suitable for use for the detection of glucose in blood samples without any pretreatment procedure. We believe that paper-based microfluidic systems may provide a wide field of usage for paper-based applications. PMID- 26363779 TI - Modification of chemical and conformational properties of natural organic matter by click chemistry as revealed by ESI-Orbitrap mass spectrometry. AB - A click reaction is reported here for the first time as a useful technique to control the conformational stability of natural organic matter (NOM) suprastructures. Click conjugates were successfully formed between a previously butynylated NOM hydrophobic fraction and a hydrophilic polyethylene glycol (PEG) amino chain. The click products were shown by size exclusion chromatography (HPSEC) hyphenated with Orbitrap mass spectrometry (MS) in electrospray ionization (ESI) (+), while precursors were visible in ESI (-). Despite their increase in molecular weight, HPSEC elution of click conjugates occurred after that of precursors, thus showing their departure from the NOM supramolecular association. This indicates that the click-conjugated NOM molecules were varied in their hydrophilic and cationic character and lost the capacity to accommodate in the original hydrophobic suprastructures. The most abundant product had the C16H30O5N4 formula, a click conjugate of butanoic acid, while other products were short-chained (C4-C8) linear unsaturated and hydroxylated carboxylic acids. Tandem MS revealed formation of triazole rings in clicked conjugates and their two fragmentations at the ester and the C-N alkyl-aryl bonds. The behavior of NOM molecules modified by click chemistry confirms that hydrophobicity and ionic charge of humic molecules play a pivotal role in stabilizing intermolecular forces in NOM. Moreover, the versatility of the click reaction may become useful to decorate NOM molecules with a variety of substrates, in order to alter NOM conformational and chemical properties and diversify its applications in the environment. PMID- 26363780 TI - Ninth Advanced Study Course on Optical Chemical Sensors--nanotechnology for (bio)chemical sensors. PMID- 26363781 TI - Clinicopathological outcomes of preoperative chemoradiotherapy using S-1 plus Irinotecan for T4 lower rectal cancer. AB - PURPOSE: To investigate the clinicopathological outcomes of patients with T4 lower rectal cancer treated using preoperative chemoradiotherapy with S-1 plus Irinotecan. METHODS: Between 2005 and 2011, 35 patients with T4M0 lower rectal cancer, diagnosed initially as T4a in 12 and as T4b in 23, were treated with 45 Gy of radiotherapy concomitantly with S-1 plus Irinotecan. The median follow-up period was 50.6 months (range 2-123 months). RESULTS: A total of 32 patients (91.4 %) completed the radiotherapy and 26 (74.3 %) completed the full chemotherapy regimen. Radical surgery was then performed in 33 (94.3 %) of the 35 patients after the exclusion of two patients, who had macroscopic residual disease. The pathological diagnosis was downstaged from T4a to ypT0-3 in all 12 of those patients (100 %) and from T4b to ypT0-4a in 20 of those 23 patients (87.0 %). The tumor regression grade of 1a/1b/2/3 (complete response) was 10/8/15/2, respectively. In terms of long-term survival, the 5-year local relapse free survival rate was 74.8 % and the recurrence-free survival rate was 52.0 %. CONCLUSIONS: This regimen may result in favorable downstaging. Moreover, in this series, pathological evidence of involvement of adjacent organs was rare following preoperative chemoradiotherapy, in the patients with disease diagnosed as T4b at the initial staging. PMID- 26363782 TI - A novel Dock8 gene mutation confers diabetogenic susceptibility in the LEW.1AR1/Ztm-iddm rat, an animal model of human type 1 diabetes. AB - AIMS/HYPOTHESIS: The LEW.1AR1-iddm rat, an animal model of human type 1 diabetes, arose through a spontaneous mutation within the inbred strain LEW.1AR1. A susceptibility locus (Iddm8) on rat chromosome 1 (RNO1) has been identified previously, which is accompanied by autoimmune diabetes and the additional phenotype of a variable CD3(+) T cell frequency. METHODS: In the present study we characterised the Iddm8 region on RNO1 in backcross strains using the genetically divergent Brown Norway (BN) and Paris (PAR) rats. Candidate genes of the Iddm8 region were sequenced for mutation analysis. RESULTS: The Iddm8 region could be subdivided by single nucleotide polymorphism (SNP) analyses. In the first region, a mutation in exon 44 of the Dock8 gene was identified resulting in an amino acid exchange in the protein from glutamine to glutamate. This exchange is unique for the LEW.1AR1-iddm rat. In the second region, a SNP was detected in exon 11 of the Vwa2 gene with an exchange from arginine to tryptophan. This SNP is also present in other rat strains. CONCLUSIONS/INTERPRETATION: The Dock8 mutation gave rise to a new type 1 diabetes rat model with very close similarity to type 1 diabetes in humans, providing a deepened insight into the impact of genes involved in diabetes development. PMID- 26363784 TI - Application of advanced machine learning methods on resting-state fMRI network for identification of mild cognitive impairment and Alzheimer's disease. AB - The study of brain networks by resting-state functional magnetic resonance imaging (rs-fMRI) is a promising method for identifying patients with dementia from healthy controls (HC). Using graph theory, different aspects of the brain network can be efficiently characterized by calculating measures of integration and segregation. In this study, we combined a graph theoretical approach with advanced machine learning methods to study the brain network in 89 patients with mild cognitive impairment (MCI), 34 patients with Alzheimer's disease (AD), and 45 age-matched HC. The rs-fMRI connectivity matrix was constructed using a brain parcellation based on a 264 putative functional areas. Using the optimal features extracted from the graph measures, we were able to accurately classify three groups (i.e., HC, MCI, and AD) with accuracy of 88.4 %. We also investigated performance of our proposed method for a binary classification of a group (e.g., MCI) from two other groups (e.g., HC and AD). The classification accuracies for identifying HC from AD and MCI, AD from HC and MCI, and MCI from HC and AD, were 87.3, 97.5, and 72.0 %, respectively. In addition, results based on the parcellation of 264 regions were compared to that of the automated anatomical labeling atlas (AAL), consisted of 90 regions. The accuracy of classification of three groups using AAL was degraded to 83.2 %. Our results show that combining the graph measures with the machine learning approach, on the basis of the rs fMRI connectivity analysis, may assist in diagnosis of AD and MCI. PMID- 26363783 TI - Protein kinase Cdelta regulates nuclear export of FOXO1 through phosphorylation of the chaperone 14-3-3zeta. AB - AIMS/HYPOTHESIS: Forkhead box protein O1 (FOXO1) is a transcription factor essential for beta cell fate. Protein kinase B-dependent phosphorylation of FOXO1 at S256 (P-FOXO1) enables its binding to 14-3-3 dimers and nuclear export. Dephosphorylated FOXO1 enters nuclei and activates pro-apoptotic genes. Since our previous observations suggest that protein kinase C delta (PKCdelta) induces nuclear accumulation of FOXO1, the underlying mechanism was examined. METHODS: In human islets, genetically modified mice and INS-1E cells apoptosis was assessed by TUNEL staining. Subcellular translocation of proteins was examined by confocal microscopy and signalling pathways were analysed by western blotting and overlay assay. RESULTS: In PKCdelta-overexpressing (PKCdelta-tg) mouse islet cells and INS-1E cells FOXO1 accumulated in nuclei, surprisingly, as P-FOXO1. PKCdelta-tg decelerated IGF-1-dependent stimulation of nuclear export, indicating that changes in export caused nuclear retention of P-FOXO1. Nuclear accumulation of P FOXO1 was accompanied by increased phosphorylation of 14-3-3zeta at S58 and reduced dimerisation of 14-3-3zeta. Palmitic acid further augmented phosphorylation of 14-3-3zeta and triggered nuclear accumulation of FOXO1 in both INS-1E and human islet cells. Furthermore, the overexpression of a phosphomimicking mutant of 14-3-3zeta (S58D) enhanced nuclear FOXO1. In accordance with the nuclear accumulation of P-FOXO1, PKCdelta overexpression alone did not increase apoptotic cell death. Additionally, insulin secretion and glucose homeostasis in PKCdelta-overexpressing mice remained unaffected. CONCLUSIONS/INTERPRETATION: These results suggest that PKCdelta-mediated phosphorylation of 14-3-3zeta contributes to the nuclear retention of FOXO1, even when FOXO1 is phosphorylated as under non-stress conditions. P-FOXO1 does not induce pro-apoptotic genes, but may rather exert beneficial effects on beta cells. PMID- 26363785 TI - Colorectal cancer DNA methylation patterns from patients in Manaus, Brazil. AB - BACKGROUND: DNA methylation is commonly linked with the silencing of the gene expression for many tumor suppressor genes. As such, determining DNA methylation patterns should aid, in times to come, in the diagnosis and personal treatment for various types of cancers. Here, we analyzed the methylation pattern from five colorectal cancer patients from the Amazon state in Brazil for four tumor suppressor genes, viz.: DAPK, CDH1, CDKN2A, and TIMP2 by employing a polymerase chain reaction (PCR) specific to methylation. Efforts in the study of colorectal cancer are fundamental as it is the third most of highest incidence in the world. RESULTS: Tumor biopsies were methylated in 1/5 (20%), 2/5 (40%), 4/5 (80%), and 4/5 (80%) for CDH1, CDKN2A, DAPK, and TIMP2 genes, respectively. The margin biopsies were methylated in 3/7 (43%), 2/7 (28%), 7/7 (100%), and 6/7 (86%) for CDH1, CDKN2A, DAPK, and TIMP2, respectively. CONCLUSIONS: Our findings showed DAPK and TIMP2 to be methylated in most samples from both tumor tissues and adjacent non-neoplastic margins; thus presenting distinct methylation patterns. This emphasizes the importance of better understanding of the relation of these patterns with cancer in the context of different populations. PMID- 26363786 TI - Imaging features of synovial chondromatosis of the spine: a review of 28 cases. AB - OBJECTIVE: To describe the radiographic, CT, and MRI appearance of synovial chondromatosis of the spine. MATERIALS AND METHODS: Radiology and pathology databases were searched for cases of spinal synovial chondromatosis from 1984 through 2013, yielding 29 patients (16 males, 13 females). The average age was 45 years. Twenty-eight patients had imaging studies available for review including seven radiographs, two myelograms, 13 CT, and 23 MRI exams. RESULTS: Cases were located in the cervical spine (16), thoracic spine (6), lumbar spine (6), and sacrum (1). Twenty-two cases (79%) had an epidural component. Eighteen (64%) had a neural foraminal component. Sixteen (57%) had a paraspinal component. The mass abutted a facet joint in 96% of cases. Nearly all (96%) showed a normal facet joint without internal erosive changes. Most (79%) showed evidence of chronic extrinsic bony erosion, usually involving the surface of the facet. Only 44% had calcifications as a dominant finding. Most patients (88%) had evidence of neural compression. On T1-weighted MRI, 80% showed intermediate or a combination of intermediate and dark signal. On T2-weighted images, 89% showed heterogeneous signal with discrete areas of dark signal. The majority (83%) showed a peripheral pattern of enhancement, usually peripheral nodular. CONCLUSIONS: Synovial chondromatosis should be considered in the differential diagnosis when evaluating an epidural and/or paraspinal mass near a facet joint, especially when there is evidence of chronic extrinsic bone erosion, dark signal or nodules on T1 and/or T2, and nonenhancing fluid or myxoid signal centrally with thin or nodular peripheral enhancement. PMID- 26363788 TI - Improving the redistribution of the security lessons in healthcare: An evaluation of the Generic Security Template. AB - CONTEXT: The recurrence of past security breaches in healthcare showed that lessons had not been effectively learned across different healthcare organisations. Recent studies have identified the need to improve learning from incidents and to share security knowledge to prevent future attacks. Generic Security Templates (GSTs) have been proposed to facilitate this knowledge transfer. The objective of this paper is to evaluate whether potential users in healthcare organisations can exploit the GST technique to share lessons learned from security incidents. METHODOLOGY: We conducted a series of case studies to evaluate GSTs. In particular, we used a GST for a security incident in the US Veterans' Affairs Administration to explore whether security lessons could be applied in a very different Chinese healthcare organisation. RESULTS: The results showed that Chinese security professional accepted the use of GSTs and that cyber security lessons could be transferred to a Chinese healthcare organisation using this approach. The users also identified the weaknesses and strengths of GSTs, providing suggestions for future improvements. CONCLUSION: Generic Security Templates can be used to redistribute lessons learned from security incidents. Sharing cyber security lessons helps organisations consider their own practices and assess whether applicable security standards address concerns raised in previous breaches in other countries. The experience gained from this study provides the basis for future work in conducting similar studies in other healthcare organisations. PMID- 26363787 TI - Ebola Virus Infection: Overview and Update on Prevention and Treatment. AB - In 2014 and 2015, the largest Ebola virus disease (EVD) outbreak in history affected large populations across West Africa. The goal of this report is to provide an update on the epidemic and review current progress in the development, evaluation and deployment of prevention and treatment strategies for EVD. Relevant information was identified through a comprehensive literature search using Medline, PubMed and CINAHL Complete and using the search terms Ebola, Ebola virus disease, Ebola hemorrhagic fever, West Africa outbreak, Ebola transmission, Ebola symptoms and signs, Ebola diagnosis, Ebola treatment, vaccines for Ebola and clinical trials on Ebola. Through 22 July 2015, a total of 27,741 EVD cases and 11,284 deaths were reported from all affected countries. Several therapeutic agents and novel vaccines for EVD have been developed and are now undergoing evaluation. Concurrent with active case investigation, contact tracing, surveillance and supportive care to patients and communities, there has been rapid progress in the development of new therapies and vaccines against EVD. Continued focus on strengthening clinical and public health infrastructure will have direct benefits in controlling the spread of EVD and will provide a strong foundation for deployment of new drugs and vaccines to affected countries when they become available. The unprecedented West Africa Ebola outbreak, response measures, and ensuing drug and vaccine development suggest that new tools for Ebola control may be available in the near future. PMID- 26363790 TI - Mobilization for HIV Voluntary Counseling and Testing Services in Vietnam: Clients' Risk Behaviors, Attitudes and Willingness to Pay. AB - A multi-site survey was conducted on a sample of 365 clients to assess their willingness to pay for HIV voluntary counseling and testing (VCT) services in Ha Noi and Nam Dinh province, two epicenters of Vietnam. By using contingent valuation technique, the results showed that most of respondents (95.1 %) were willing to pay averagely 155 (95 % CI 132-177) thousands Vietnam Dong (~US $7.75, 2013) for a VCT service. Clients who were female, had middle income level, and current opioid users were willing to pay less; meanwhile clients who had university level of education were willing to pay more for a VCT service. The results highlighted the high rate of willingness to pay for the service at a high amount by VCT clients. These findings contribute to the implementation of co payment scheme for VCT services toward the financial sustainability of HIV/AIDS programs in Vietnam. PMID- 26363789 TI - Correlates of Seroadaptation Strategies Among Black Men Who have Sex with Men (MSM) in 4 US Cities. AB - We assessed associations of demographic, psychosocial, and substance use factors with seroadaptation strategies among 835 BMSM in four US cities. Seroadaptation strategies were practiced by 59.8 % of men, with 10.5 % practicing 100 % condom use, 26.5 % serosorting, 7.2 % condom serosorting, and 15.6 % seropositioning. In multivariable analyses, compared to men who used no seroadaptation strategies, serosorters were older, were less likely to be HIV infected, had fewer male sex partners, and had higher levels of social support and sexual self-efficacy. Condom serosorters had less psychological distress, were more likely to use methamphetamine, and had higher levels of sexual self-efficacy. Seropositioners were older, were less likely to be HIV infected, to have a main partner, and report alcohol/drug use with sex, while having higher levels of sexual self efficacy. Seroadaptation practices among BMSM need to be considered to address perceived safer sex strategies and strengthen access to a broader reach of culturally-relevant prevention efforts. PMID- 26363791 TI - Physiological amyloid-beta clearance in the periphery and its therapeutic potential for Alzheimer's disease. AB - Amyloid-beta (Abeta) plays a pivotal role in the pathogenesis of Alzheimer's disease (AD). The physiological capacity of peripheral tissues and organs in clearing brain-derived Abeta and its therapeutic potential for AD remains largely unknown. Here, we measured blood Abeta levels in different locations of the circulation in humans and mice, and used a parabiosis model to investigate the effect of peripheral Abeta catabolism on AD pathogenesis. We found that blood Abeta levels in the inferior/posterior vena cava were lower than that in the superior vena cava in both humans and mice. In addition, injected (125)I labeled Abeta40 was located mostly in the liver, kidney, gastrointestinal tract, and skin but very little in the brain; suggesting that Abeta derived from the brain can be cleared in the periphery. Parabiosis before and after Abeta deposition in the brain significantly reduced brain Abeta burden without alterations in the expression of amyloid precursor protein, Abeta generating and degrading enzymes, Abeta transport receptors, and AD-type pathologies including hyperphosphorylated tau, neuroinflammation, as well as neuronal degeneration and loss in the brains of parabiotic AD mice. Our study revealed that the peripheral system is potent in clearing brain Abeta and preventing AD pathogenesis. The present work suggests that peripheral Abeta clearance is a valid therapeutic approach for AD, and implies that deficits in the Abeta clearance in the periphery might also contribute to AD pathogenesis. PMID- 26363793 TI - Testing the Validity of a Cognitive Behavioral Model for Gambling Behavior. AB - Currently, cognitive behavioral therapies appear to be one of the most studied treatments for gambling problems and studies show it is effective in treating gambling problems. However, cognitive behavior models have not been widely tested using statistical means. Thus, the aim of this study was to test the validity of the pathways postulated in the cognitive behavioral theory of gambling behavior using structural equation modeling (AMOS 20). Several questionnaires assessing a range of gambling specific variables (e.g., gambling urges, cognitions and behaviors) and gambling correlates (e.g., psychological states, and coping styles) were distributed to 969 participants from the community. Results showed that negative psychological states (i.e., depression, anxiety and stress) only directly predicted gambling behavior, whereas gambling urges predicted gambling behavior directly as well as indirectly via gambling cognitions. Avoidance coping predicted gambling behavior only indirectly via gambling cognitions. Negative psychological states were significantly related to gambling cognitions as well as avoidance coping. In addition, significant gender differences were also found. The results provided confirmation for the validity of the pathways postulated in the cognitive behavioral theory of gambling behavior. It also highlighted the importance of gender differences in conceptualizing gambling behavior. PMID- 26363792 TI - The molecular aspects of chordoma. AB - Chordomas are one of the rarest bone tumors, and they originate from remnants of embryonic notochord along the spine, more frequently at the skull base and sacrum. Although they are relatively slow growing and low grade, chordomas are highly recurrent, aggressive, locally invasive, and prone to metastasize to the lungs, bone, and the liver. Chordomas highly and generally show a dual epithelial mesenchymal differentiation. These tumors resist chemotherapy and radiotherapy; therefore, radical surgery and high-dose radiation are the most used treatments, although there is no standard way to treat the disease. The molecular biology process behind the initiation and progression of a chordoma needs to be revealed for a better understanding of the disease and to develop more effective therapies. Efforts to discover the mysteries of these molecular aspects have delineated several molecular and genetic alterations in this tumor. Here, we review and describe the emerging insights into the molecular landscape of chordomas. PMID- 26363794 TI - Synthesis of diverse pyrazole-4-sulfonyl chlorides starting from 2 (benzylthio)malonaldehyde. AB - A series of pyrazole-4-sulfonyl chlorides was obtained by a convenient 2-step method starting from synthetically available 2-(benzylthio)malonaldehyde. The method can be applied for the effective multi-gram synthesis of diverse pyrazole containing sulfonyl chlorides which are mostly not available by other methods. PMID- 26363795 TI - The Role of MAPT in Neurodegenerative Diseases: Genetics, Mechanisms and Therapy. AB - Microtubule-associated protein tau (MAPT) is a gene responsible for encoding tau protein, which is tightly implicated in keeping the function of microtubules and axonal transport. Hyperphosphorylated tau protein participates in the formation of neurofibrillary tangles (NFTs), which characterize many neurodegenerative disorders termed tauopathies. Genome-wide association studies (GWAS) have demonstrated numerous single nucleotide polymorphisms (SNPs) located in MAPT associated with various neurodegenerative diseases. Thus, it has been presumed that MAPT plays a crucial role in pathogenesis of neurodegeneration via affecting the structure and function of tau. Here, we review the advanced studies to summarize the biochemical properties of MAPT and its encoded protein, as well as the genetics and epigenetics of MAPT in neurodegeneration. Finally, given the potential mechanisms of MAPT to neurodegeneration pathogenesis, targeting MAPT and tau might present significant treatments of MAPT mutation-related neurodegeneration. Affirmatively, the identification of MAPT is extremely beneficial for improving our understanding of the pathogenesis of various neurodegenerative diseases and developing the mechanism-based therapies. PMID- 26363796 TI - Lesion Expansion in Experimental Demyelination Animal Models and Multiple Sclerosis Lesions. AB - Gray matter pathology is an important aspect of multiple sclerosis (MS) pathogenesis and disease progression. In a recent study, we were able to demonstrate that the higher myelin content in the white matter parts of the brain is an important variable in the neuroinflammatory response during demyelinating events. Whether higher white matter myelination contributes to lesion development and progression is not known. Here, we compared lesion size of intra-cortical vs. white matter MS lesions. Furthermore, dynamics of lesion development was compared in the cuprizone and lysophosphatidylcholine models. We provide clear evidence that in the human brain, white matter lesions are significantly increased in size as compared to intra-cortical gray matter lesions. In addition, studies using the cuprizone mouse model revealed that the autonomous progression of white matter lesions is more severe compared to that in the gray matter. Focal demyelination revealed that the application of equal amounts of lysophosphatidylcholine results in more severe demyelination in the white compared to the gray matter. In summary, lesion progression is most intense in myelin-rich white matter regions, irrespective of the initial lesion trigger mechanism. A better understanding of myelin debris-triggered lesion expansion will pave the way for the development of new protective strategies in the future. PMID- 26363797 TI - IRAS Modulates Opioid Tolerance and Dependence by Regulating MU Opioid Receptor Trafficking. AB - Imidazoline receptor antisera-selected (IRAS) protein, the mouse homologue named Nischarin, was found to target to early endosomes with properties of sorting nexins in vitro. Recently, we generated IRAS knockout mice and found IRAS deficiency exacerbated the analgesic tolerance and physical dependence caused by opioids, suggesting that IRAS plays a role in regulating MU opioid receptor (MOR) functions. In the present study, we found that IRAS interacts with MOR and regulates MOR trafficking in vitro. In the CHO or HEK293 cells co-expressing MOR and IRAS, IRAS, through its PX domain, interacted with MOR. The interaction facilitated the recycling of internalized MOR and prevented MOR downregulation induced by DAMGO, the MOR agonist. Functionally, IRAS accelerated MOR resensitization and attenuated DAMGO-induced MOR desensitization, which is believed as one of mechanisms mediating opioid tolerance and dependence. Taken together, we propose that IRAS is a new MOR interacting protein and regulates agonist-induced trafficking of MOR via sorting internalized MOR to the recycling pathway, which may be a molecular mechanism underlying IRAS modulating opioid tolerance and dependence. PMID- 26363798 TI - Transcription of subtelomere tandemly repetitive DNA in chicken embryogenesis. AB - Transcription of tandemly repetitive DNA in embryogenesis seems to be of special interest due to a crucial role of non-coding RNAs in many aspects of development. However, only a few data are available on tandem repeats transcription at subtelomere regions of chromosomes during vertebrate embryogenesis. To reduce this gap, we examined stage and tissue-specific pattern of subtelomeric PO41 (pattern of 41 bp) tandem repeat transcription during embryogenesis of chicken (Gallus gallus domesticus). Using whole-mount RNA fluorescent in situ hybridization and reverse transcription PCR with specific primers, we demonstrated that both strands of PO41 repeat are transcribed at each of the studied stages of chicken embryo development: from 7-8 HH to 20 HH stages. Subtelomere-derived transcripts localize in the nuclei of all cell types and throughout the all embryonic bodies: head, somites, tail, wings and buds. In embryo-dividing cells and cultured embryonic fibroblasts, PO41 RNAs envelop terminal regions of chromosomes. PO41-containing RNAs are predominantly single stranded and can be polyadenylated, indicating appearance of non-nascent form of subtelomeric transcripts. PO41 repeat RNAs represent a rare example of ubiquitously transcribed non-coding RNAs, such as Xist/XIST RNA or telomere repeat-containing RNA. Distribution of PO41 repeat transcripts at different stages of embryo development and among cell types has extremely uniform pattern, indicating on possible universal functions of PO41 non-coding RNAs. PMID- 26363799 TI - Completing the human genome: the progress and challenge of satellite DNA assembly. AB - Genomic studies rely on accurate chromosome assemblies to explore sequence-based models of cell biology, evolution and biomedical disease. However, even the extensively studied human genome has not yet reached a complete, 'telomere-to telomere', chromosome assembly. The largest assembly gaps remain in centromeric regions and acrocentric short arms, sites known to contain megabase-sized arrays of tandem repeats, or satellite DNAs. This review aims to briefly address the progress and challenges of generating correct assemblies of satellite DNA arrays. Although the focus is placed on the human genome, many concepts presented here are applicable to other genomes. PMID- 26363800 TI - Short interspersed DNA elements and miRNAs: a novel hidden gene regulation layer in zebrafish? AB - In this study, we investigated by in silico analysis the possible correlation between microRNAs (miRNAs) and Anamnia V-SINEs (a superfamily of short interspersed nuclear elements), which belong to those retroposon families that have been preserved in vertebrate genomes for millions of years and are actively transcribed because they are embedded in the 3' untranslated region (UTR) of several genes. We report the results of the analysis of the genomic distribution of these mobile elements in zebrafish (Danio rerio) and discuss their involvement in generating miRNA gene loci. The computational study showed that the genes predicted to bear V-SINEs can be targeted by miRNAs with a very high hybridization E-value. Gene ontology analysis indicates that these genes are mainly involved in metabolic, membrane, and cytoplasmic signaling pathways. Nearly all the miRNAs that were predicted to target the V-SINEs of these genes, i.e., miR-338, miR-9, miR-181, miR-724, miR-735, and miR-204, have been validated in similar regulatory roles in mammals. The large number of genes bearing a V SINE involved in metabolic and cellular processes suggests that V-SINEs may play a role in modulating cell responses to different stimuli and in preserving the metabolic balance during cell proliferation and differentiation. Although they need experimental validation, these preliminary results suggest that in the genome of D. rerio, as in other TE families in vertebrates, the preservation of V SINE retroposons may also have been favored by their putative role in gene network modulation. PMID- 26363801 TI - Association of elevated glycosylated hemoglobin A1c with hyperfiltration in a middle-aged and elderly Chinese population with prediabetes or newly diagnosed diabetes: a cross-sectional study. AB - BACKGROUND: To examine whether elevated glycosylated hemoglobin A1c (HbA1c) is associated with hyperfiltration in a middle-aged and elderly Chinese population. METHODS: Anthropometric and biochemical examinations were performed in 2491 individuals from the general population, aged 40-79 years, who participated in the Huaian Diabetes Prevention Program. The estimated glomerular filtration rate (eGFR) was calculated from creatinine levels using the CKD-EPI formula. Hyperfiltration was defined as eGFR >90(th) percentile. RESULTS: After adjustment [for age, gender, waistline, body mass index, blood pressure, smoking, alcohol consumption, cholesterol, log(triglycerides), high-density lipoprotein, low density lipoprotein, serum uric acid, sodium intake, hypertension, and use of angiotensin converting enzyme inhibitors or angiotensin receptor blockers], HbA1c and fasting plasma glucose (FPG) were found to be independently positively associated with eGFR. Additionally, after multivariate adjustment, the odds ratios (95 % CI) for hyperfiltration calculated for a 1-unit increase in HbA1c and FPG were 1.396 (1.089-1.790) and 1.306 (1.117-1.526), respectively. Compared with participants with HbA1c levels <5.7%, the odds ratios (95 % CI) for hyperfiltration were 2.344 (1.025-5.364) in participants with HbA1c levels of 6.21-6.49%, and 2.965 (1.537-5.720) in those with HbA1c levels >= 6.5%. CONCLUSION: Elevated HbA1c (>= 6.21%) is associated with an increased odds of hyperfiltration in middle-aged and elderly Chinese. Longitudinal studies are needed to explore whether hyperfiltration increases the odds of diabetic nephropathy in individuals with prediabetes. PMID- 26363802 TI - Update on the Medical Management of Crohn's Disease. AB - The medical management of Crohn's disease is a rapidly evolving field with expanding therapeutic drug options and treatment strategies. In addition to corticosteroids, immunomodulators, and anti-tumor necrosis (anti-TNF) agents, a new anti-adhesion medication (vedolizumab) has been approved. Individualized patient-based dosing of immunomodulators and biologic agents is now possible with therapeutic drug monitoring (TDM). There is a changing paradigm in treatment goals to achieve deeper remission identified by composite clinical and endoscopic endpoints. More aggressive treatment strategies in the postoperative setting have been proposed due to emerging data on medication efficacy in this setting. Management algorithms that stratify CD patients into risk groups to balance treatment benefit against adverse events and costs are being developed to translate research into clinical practice. This review provides an update on these new developments for practicing gastroenterologists. PMID- 26363804 TI - Subxiphoid video-assisted thoracoscopic surgery versus standard video-assisted thoracoscopic surgery for anatomic pulmonary lobectomy. AB - BACKGROUND: A subxiphoid surgical approach to thoracic cavity operations has potential advantages such as preventing injuries to intercostal nerves and vessels due to the bypass of the intercostal space during thoracic surgery. The aim of this study was to compare the feasibility and efficacy of the subxiphoid and standard transthoracic approaches for anatomic pulmonary lobectomy in a canine model. METHODS: Nineteen dogs were assigned for pulmonary lobectomy using either the subxiphoid (n = 10) or standard transthoracic approaches (n = 9). Each group underwent thoracic exploration and anatomic pulmonary lobectomy. Subxiphoid thoracoscopy was performed with a flexible bronchoscope via a 3-cm incision over the xiphoid process. In the conventional thoracoscopy group, approach to the thoracic cavity was obtained through a 3-cm incision over the seventh intercostal space. Physiological parameters (respiratory rate and body temperature) and blood samples (white blood cell counts and arterial blood gases) were collected during the preoperative and postoperative periods. Surgical outcomes data (operating time, operative complications, and body weight gain) were also collected and compared between the groups. The animals were sacrificed 14 d after surgery for necropsy evaluations. RESULTS: Anatomic pulmonary lobectomy was successfully performed without intraoperative and postoperative complications in all animals. There were no significant differences in the mean operating times or weight gain after surgery between the subxiphoid and the standard transthoracic approach groups. In terms of physiological and pulmonary parameters, there were no observed differences between the two surgical groups for respiratory rate, body temperature, white blood cell counts, and arterial blood gases at any time during the study. Necropsy confirmed the success of lobectomy without complication in all studied animals. CONCLUSIONS: This study demonstrated that the subxiphoid approach was comparable with the standard transthoracic approach for anatomic pulmonary lobectomy, in terms of feasibility and effectiveness. PMID- 26363805 TI - The effect of CoolClot hemostatic agent on skin wound healing in rats. AB - BACKGROUND: Hemostatic agents can play a key role in controlling severe hemorrhage after trauma. Previously, some criteria have been defined for improving the quality of these products; one of them is that the hemostat causes no further tissue injury. CoolClot is a recently introduced hemostatic agent that its effects on wound healing have not yet been examined, which this study aims to address. MATERIALS AND METHODS: Thirty-four adult male Sprague-Dawley rats were assigned randomly to two groups (n = 17): a study group where CoolClot hemostatic agent was applied on their wounds, and a control group whose wounds were washed only with sterile saline. The rats underwent dorsal full-thickness skin excisional wounds (20 mm diameter). On day 12 after wounding, seven rats were chosen in a random manner from each of the groups of study and control, and their skin biopsies from the wound sites were sent for histologic examination. Skin samples of the remaining rats in each group were taken on the 21st d after wound creation. Wound healing was also monitored photographically. In addition, wound surface temperature after wounding, and the application of CoolClot was recorded. RESULTS: There was no significant difference between the groups of study and control regarding the examined histopathologic parameters. The maximum increase in wound surface temperature was 1.56 degrees C. CONCLUSIONS: One-time topical usage of CoolClot has no significant negative effect on the wound healing process. In addition, no significant increase in wound surface temperature will occur after the application of this agent. PMID- 26363806 TI - Ultrasound-guided transversus abdominis plane block in patients undergoing open inguinal hernia repair: 0.125% bupivacaine provides similar analgesic effect compared to 0.25% bupivacaine. AB - STUDY OBJECTIVE: To evaluate the effectiveness of 0.125% bupivacaine compared to 0.25% bupivacaine for ultrasound-guided transversus abdominis plane (TAP) block in patients undergoing open inguinal hernia repair. DESIGN: Randomized, double blind study. SETTING: Educational and research hospital. PATIENTS: Forty adult patients of American Society of Anesthesiologists physical status I-III undergoing elective primary unilateral open inguinal hernia repair under spinal anesthesia. INTERVENTIONS: Patients in group I received 20 mL of 0.25% bupivacaine, whereas patients in group II received 20 mL of 0.125% bupivacaine for TAP block at the end of the surgery. MEASUREMENTS: Pain intensity was assessed at rest and during coughing using 10-cm visual analog scale score at 5, 15, 30, and 45 minutes and 1, 2, 4, 6, 12, and 24 hours after TAP block. Morphine consumption and time to first morphine requirement were recorded. MAIN RESULTS: Visual analog scale scores at rest and during coughing were not significantly different between groups at all time points measured. Twenty-four hours of morphine consumption (7.72+/-7.33 mg in group I and 6.06+/-5.20 mg in group II; P=.437) and time to first morphine requirement (182.35+/-125.16 minutes in group I and 143.21+/-87.28 minutes in group II; P=.332) were not different between groups. CONCLUSIONS: 0.125% Bupivacaine provides similar analgesic effect compared to 0.25% bupivacaine for ultrasound-guided TAP block in patients undergoing open inguinal hernia repair. PMID- 26363803 TI - The relationship between COPD and lung cancer. AB - Both COPD and lung cancer are major worldwide health concerns owing to cigarette smoking, and represent a huge, worldwide, preventable disease burden. Whilst the majority of smokers will not develop either COPD or lung cancer, they are closely related diseases, occurring as co-morbidities at a higher rate than if they were independently triggered by smoking. Lung cancer and COPD may be different aspects of the same disease, with the same underlying predispositions, whether this is an underlying genetic predisposition, telomere shortening, mitochondrial dysfunction or premature aging. In the majority of smokers, the burden of smoking may be dealt with by the body's defense mechanisms: anti-oxidants such as superoxide dismutases, anti-proteases and DNA repair mechanisms. However, in the case of both diseases these fail, leading to cancer if mutations occur or COPD if damage to the cell and proteins becomes too great. Alternatively COPD could be a driving factor in lung cancer, by increasing oxidative stress and the resulting DNA damage, chronic exposure to pro-inflammatory cytokines, repression of the DNA repair mechanisms and increased cellular proliferation. Understanding the mechanisms that drive these processes in primary cells from patients with these diseases along with better disease models is essential for the development of new treatments. PMID- 26363807 TI - A comparative study of four independent methods to measure LDL particle concentration. AB - BACKGROUND: Low-density lipoprotein particle concentration (LDL-P) is generally more predictive of clinical cardiovascular endpoints than LDL cholesterol (LDL C). Few studies have directly compared multiple LDL-P methods, particularly with ultracentrifugation. OBJECTIVE: Examine comparability and precision of 4 LDL-P methods. METHODS: We divided serum from 48 subjects into blinded triplicates and measured LDL-P in 3 separate laboratories by 4 methods: ultracentrifugation (reference method), a novel electrophoretic method, and nuclear magnetic resonance spectroscopy (NMR) by 2 independent methods: a 400 MHz Vantera((r)) instrument supplied by Liposcience (LS-NMR) and operated at ARUP Laboratories, and a 600 MHz Bruker instrument (ASCEND 600) operated at Health Diagnostic Laboratory (HD-NMR). RESULTS: Of the 4 methods, ultracentrifugation was the most precise and LS-NMR the least; the latter had a significantly greater CV (p < 0.0001) as compared with all 3 of the other methods, although all CVs were clinically acceptable. The electrophoretic method showed similar precision to ultracentrifugation, while HD-NMR was intermediate. The HD-NMR had the slope closest to 1 (0.90, 95% CI 0.71 to 1.09) and the intercept closest to 0 (-48, 353 to 256) compared to the ultracentrifugation method in Deming regression models. While the two NMR methods correlated well (r = 0.95) with each other and had a slope equivalent to 1 (1.08, 0.98 to 1.19), their intercept in Deming regression excluded 0 (194, 53 to 335) indicating a vertical shift between the two methods. CONCLUSIONS: This LDL-P method comparison may prove useful for future research and clinical applications. PMID- 26363808 TI - Effect of a new PPAR-gamma agonist, lobeglitazone, on neointimal formation after balloon injury in rats and the development of atherosclerosis. AB - OBJECTIVE: The ligand-activated transcription factor peroxisome proliferator activated receptor gamma (PPARgamma) is a key factor in adipogenesis, insulin sensitivity, and cell cycle regulation. Activated PPARgamma might also have anti inflammatory and antiatherogenic properties. We tested whether lobeglitazone, a new PPARgamma agonist, might protect against atherosclerosis. METHODS: A rat model of balloon injury to the carotid artery, and high-fat, high-cholesterol diet-fed apolipoprotein E gene knockout (ApoE(-/-)) mice were studied. RESULTS: After the balloon injury, lobeglitazone treatment (0.3 and 0.9 mg/kg) caused a significant decrease in the intima-media ratio compared with control rats (2.2 +/ 0.9, 1.8 +/- 0.8, vs. 3.3 +/- 1.2, P < 0.01). Consistent with this, in ApoE(-/-) mice fed a high-fat diet, lobeglitazone treatment (1, 3, and 10 mg/kg) for 8 weeks reduced atherosclerotic lesion sizes in the aorta compared with the control mice in a dose-dependent manner. Treatment of vascular smooth muscle cells with lobeglitazone inhibited proliferation and migration and blocked the cell cycle G0/G1 to S phase progression dose-dependently. In response to lobeglitazone, tumor necrosis factor alpha (TNFalpha)-induced monocyte-endothelial cell adhesion was decreased by downregulating the levels of adhesion molecules. TNFalpha induced nuclear factor kappa-B (NF-kappaB) p65 translocation into the nucleus was also blocked in endothelial cells. Insulin resistance was decreased by lobeglitazone treatment. Circulating levels of high sensitivity C-reactive protein and monocyte chemoattractant protein-1 were decreased while adiponectin levels were increased by lobeglitazone in the high-fat diet-fed ApoE(-/-) mice. CONCLUSION: Lobeglitazone has antiatherosclerotic properties and has potential for treating patients with diabetes and cardiovascular risk. PMID- 26363809 TI - Expert opinion on first-line therapy in the treatment of castration-resistant prostate cancer. AB - Treatment of metastatic castration-resistant prostate cancer (mCRPC) has been revolutionized in recent years. It is well known that androgen receptor is still active in most patients with disease progression and serum testosterone levels <50 ng/dL. Moreover, further hormonal maneuvers, either through decreasing androgen levels (abiraterone) or by targeting the androgen receptor (AR) pathway (enzalutamide), prolong survival. In addition, a new cytostatic able to overcome docetaxel resistance, cabazitaxel, and the radioisotope radium 223 have been incorporated to the armamentarium of mCRPC. mCRPC is not only a heterogeneous tumor, it changes over time developing neuroendocrine features or selection of clones resistant to hormonal maneuvers. In addition, the multiplicity of current treatments, make it necessary to design algorithms that help the specialist to choose the most appropriate treatment for a particular patient. The lack of randomized trials comparing face to face the different available options limit the scope of this review. In this article, the authors describe the prognostic factors for first line therapy in patients with mCRPC, and propose a treatment algorithm for mCRPC based on the levels of scientific evidence available and, if not available, on the consensus between medical professionals. Finally, the panel discuss how to define progressive disease in the setting of mCRPC and treatment with targeted therapies. PMID- 26363810 TI - Diamond-shaped anastomosis for supermicrosurgical side-to-side lymphaticovenular anastomosis. PMID- 26363811 TI - Frontalis muscle transfer technique for correction of severe congenital blepharoptosis in Chinese patients: An analysis of surgical outcomes related to frontalis muscle function. AB - AIM: The aim of this study is to evaluate the surgical outcomes related to frontalis muscle function using the frontalis muscle transfer technique in Chinese patients with severe congenital blepharoptosis and poor levator function. MATERIALS AND METHOD: Between December 2003 and December 2011, using the frontalis muscle transfer technique, 37 patients of Chinese origin underwent surgery on 53 eyelids. The frontalis muscle function was assessed and categorized as poor (excursion <= 7 mm) and good (excursion > 7 mm) before the surgery. The results, including complications of the treatment procedure, were followed up and evaluated. Using the Cochran-Mantel-Haenszel statistic, the preoperative ptosis severity was compared with the degree of ptosis correction, and the preoperative frontalis muscle function was compared with the degree of ptosis correction using Fisher's exact test for paired data. A two-sided value of p < 0.05 was considered statistically significant. RESULTS: Of the total eyelids considered, sufficient postoperative correction of ptosis was achieved in 43 eyelids (81.1%), while the correction was insufficient in 10 eyelids (18.9%). Fifteen (28.3%) eyelids were either overcorrected (n = 5) or undercorrected (n = 10). The rate of lagophthalmos was 3.8%. Eyelids with preoperative frontalis muscle function >7 mm had a higher rate of sufficient correction in comparison to those with preoperative frontalis muscle function <=7 mm (91.2% vs. 63.2%; p < 0.05). However, postoperative ptosis correction had no relationship with preoperative ptosis severity. CONCLUSION: The frontalis muscle is the main motor muscle used in the correction of severe blepharoptosis via the frontalis muscle transfer technique. Although the technique is considered to be an effective surgical method for the correction of severe blepharoptosis, the outcome of the correction procedure depends on the preoperative frontalis muscle function of the patient. PMID- 26363813 TI - Functional connectivity change across multiple cortical networks relates to episodic memory changes in aging. AB - A major task of contemporary cognitive neuroscience of aging is to explain why episodic memory declines. Change in resting-state functional connectivity (rsFC) could be a mechanism accounting for reduced function. We addressed this through 3 studies. In study 1, 119 healthy participants (20-83 years) were followed for 3.5 years with verbal recall testing and magnetic resonance imaging. Independent of atrophy, recall change was related to change in rsFC in anatomically widespread areas. Striking age-effects were observed in that a positive relationship between rsFC and memory characterized older participants while a negative relationship was seen among the younger and middle-aged. This suggests that cognitive consequences of rsFC change are not stable across age. In study 2 and 3, the age dependent differences in rsFC-memory relationship were replicated by use of a simulation model (study 2) and by a cross-sectional experimental recognition memory task (study 3). In conclusion, memory changes were related to altered rsFC in an age-dependent manner, and future research needs to detail the mechanisms behind age-varying relationships. PMID- 26363815 TI - OMICS in Plant Disease Resistance. AB - The term OMICS, which look into the global profiling and analysis of various cellular molecules, has gained new heights with the advancement of next generation sequencing and mass spectrometry technologies. It has broader implication in genetic improvement of crops for resistance against various diseases of economic significance. This focus issue entitled OMICS in Plant Disease Resistance highlights the implication of OMICS (genomics, transcriptomics, proteomics and metabolomics) in agricultural research. PMID- 26363814 TI - A mouse model of endocardial fibroelastosis. AB - BACKGROUND: Endocardial fibroelastosis (EFE) is a pathologic condition of abnormal deposition of collagen and elastin within the endocardium of the heart. It is seen in conjunction with a variety of diseases including hypoplastic left heart syndrome and viral endocarditis. While an experimental model using heterotopic heart transplant in rats has been described, we sought to fully describe a mouse model that can be used to further elucidate the potential mechanisms of and treatments for EFE. MATERIALS AND METHODS: The hearts of 2-day old C57BL/6 mice were transplanted into the abdomen of 7-week-old C57BL/6 mice. At 2 weeks, the hearts were harvested and histologic analysis was performed using hematoxylin and eosin, Masson's trichrome, Russell-Movat's pentachrome, Picrosirius red, Hart's, Verhoeff-Van Gieson, and Weigert's Resorcin-Fuchsin stains. Additionally, one heart was analyzed using transmission electron microscopy (TEM). RESULTS: Specimens demonstrated abnormal accumulation of both collagen and elastin within the endocardium with occasional expansion into the myocardium. Heterogeneity in extracellular matrix deposition was noted in the histologic specimens. In addition, TEM demonstrated the presence of excess collagen within the endocardium. CONCLUSIONS: The heterotopic transplantation of an immature heart into a mouse results in changes consistent with EFE. This model is appropriate to investigate the etiology and treatment of EFE. PMID- 26363812 TI - Pitx3 deficiency produces decreased dopamine signaling and induces motor deficits in Pitx3(-/-) mice. AB - Midbrain dopamine (DA) neurons are involved in cognition, control of motor activity, and emotion-related behaviors. Degeneration of DA neurons particularly in the substantia nigra is a hallmark of Parkinson's disease. The homeobox transcription factor, Pitx3, plays a critical role in the development, function, and maintenance of midbrain DA neurons. We found that in young adult Pitx3-null mice, Pitx3(-/-), there was decreased tyrosine hydroxylase staining, indicating a loss of DA neurons particularly in the substantia nigra. In addition, fast-scan cyclic voltammetry and microdialysis assays of DA release indicated that the lack of Pitx3 caused a significant reduction of striatal DA release. Tonic DA release was impaired more significantly than the phasic DA release induced by burst firing of DA neurons. Furthermore, behavioral tests revealed that Pitx3(-/-) mice displayed abnormal motor activities, including impaired motor coordination and decreased locomotion. In summary, these data provide further evidence that Pitx3 is specifically required for DA-related function and, if impaired, Pitx3 could contribute during the pathogenesis of Parkinson's disease. PMID- 26363816 TI - Comparative evaluation of the effect of cyclodextrins and pH on aqueous solubility of apigenin. AB - The aqueous solubility of a flavonoid, apigenin, was studied in the presence of first generation cyclodextrins (alpha-CyD, beta-CyD, gamma-CyD), ionic and nonionic synthetic derivatives of beta-CyD, namely SBE-beta-CyD, HP-beta-CyD and RM-beta-CyD at various physiological pH. The order of solubility enhancement was as follows: RM-beta-CyD>SBE-beta-CyD>gamma-CyD>HP-beta-CyD>beta-CyD>alpha-CyD. The phase solubility diagrams of HP-beta-CyD and SBE-beta-CyD indicated Higuchi AL subtype behavior, suggesting 1:1 stoichiometry of the complex. In contrast, AP subtype, so higher order complex formation can be assumed in the case of RM-beta CyD and gamma-CyD. The formation of inclusion complexes has been confirmed by absorption and fluorescence spectroscopic measurements. Increased antioxidant activity was observed due to the inclusion complexes. These results prove that synthetic derivatives of beta-CyD will be potentially useful excipients in the development of drug delivery systems for healthcare products containing flavonoids. PMID- 26363817 TI - Rice Responses and Resistance to Planthopper-Borne Viruses at Transcriptomic and Proteomic Levels. AB - Rice (Oryza sativa) is one of the most important cereal crops in the world, especially in Asian areas. Rice virus diseases are considered as the most serious threat to rice yields. Most rice viruses are transmitted by hemipteran insects such as planthoppers and leafhoppers. In Asia five rice viruses are transmitted mainly by three planthopper species in a persistent manner: Rice stripe virus, Rice black-streaked dwarf virus, Rice ragged stunt virus, Rice grassy stunt virus, and Southern rice black-streaked dwarf virus. In rice antivirus studies, several individual genes have been shown to function in rice resistance to viruses. Since plant responses to viral infection are complex, system-level omic studies are required to fully understand the responses. Recently more and more omic studies have appeared in the literatures on relationships between planthoppers and viruses, employing microarray, RNA-Seq, small RNA deep sequencing, degradome sequencing, and proteomic analysis. In this paper, we review the current knowledge and progress of omic studies in rice plant responses and resistance to four planthopper-borned viruses. We also discuss progress in the omic study of the interactions of planthoppers and rice viruses. Future research directions and translational applications of fundamental knowledge of virus-vector-rice interactions are proposed. PMID- 26363818 TI - [Acute anterior myocardial infarction as presenting feature of antiphospholipid syndrome related lupus arthritis]. AB - INTRODUCTION: Antiphospholipid syndrome is an autoimmune disorder causing venous and arterial thrombosis. Acute coronary complications are rare but potentially dramatic. CASE REPORT: We report a 39-year-old woman who presented with an acute anterior myocardial infarction after intravenous corticosteroids as part of the treatment of lupus arthritis and revealing antiphospholipid syndrome. Emergency coronary angiography was performed with drug-eluting stent angioplasty despite the need for anticoagulation and dual antiplatelet therapy. CONCLUSION: Antiplatelet and anticoagulant therapy management is pivotal in patients with antiphospholipid syndrome and acute coronary syndrome to prevent thrombosis recurrence. PMID- 26363819 TI - Serum alkaline phosphatase as a predictor of worsening renal function in patients with acute decompensated heart failure. AB - BACKGROUND: Venous congestion has come into focus as an important hemodynamic factor for worsening renal function (WRF) in patients with acute decompensated heart failure (ADHF). Serum alkaline phosphatase (ALP) was reported as a biological marker of liver congestion in ADHF. The purpose of this study was to determine whether ALP is a predictor of WRF in patients with ADHF. METHODS: We enrolled consecutive patients admitted to a single cardiovascular center with ADHF, and defined WRF as an increase in creatinine of >0.3 mg/dl during hospitalization and chronic kidney disease (CKD) as an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2). The patients were classified into tertiles by ALP level (<203, 203-278, and >278 IU/L). RESULTS: A total of 972 patients (mean age, 76+/-13 years; 54% male) were retrospectively analyzed. WRF was identified in 132 patients (13.6%). In multivariate logistic regression analysis, baseline CKD [odds ratio (OR) 2.46, 95% confidence interval (CI) 1.48 4.08, p<0.001], serum albumin (OR 0.52, 95% CI 0.35-0.77, p=0.001), and diabetes (OR 2.07, 95% CI 1.37-3.12, p<0.001) were associated with WRF. Compared with the lowest tertile (ALP <203 IU/L), an adjusted OR of WRF was 1.69 (95% CI 1.02-2.79, p=0.04) in the middle tertile (ALP, 203-278 IU/L) and 1.95 (95% CI 1.20-3.21, p=0.008) in the highest tertile (ALP >278 IU/L). CONCLUSION: Serum ALP is an independent predictor of WRF in the clinical course of ADHF. PMID- 26363820 TI - The value of cardiac magnetic resonance and distribution of late gadolinium enhancement for risk stratification of sudden cardiac death in patients with hypertrophic cardiomyopathy. AB - BACKGROUND: The presence of late gadolinium enhancement (LGE) in hypertrophic cardiomyopathy (HCM) is associated with worse clinical outcome and the extent of LGE predicts the increased risk of sudden cardiac death (SCD). Limited data exist regarding the distribution of LGE. We attempted to verify whether the presence of LGE outside the interventricular insertion points carries additional risk for patients with HCM. METHODS: In this prospective study, 328 patients with HCM, who underwent cardiac magnetic resonance (CMR) were enrolled. Five major risk factors for SCD were assessed in all patients. The median follow-up was 37 months. RESULTS: LGE was detected in 226 (68.9%) patients. In 70 (21.3%) patients it was present only at the interventricular insertion points - LGE (+) group, while in 156 (47.6%) it was noted in other locations - LGE (++) group. Primary endpoint defined as SCD or appropriate implantable cardioverter-defibrillator intervention occurred in 14 (4.3%) patients, one in LGE (+) and 13 in LGE (++). In multivariable analysis including five traditional risk factors and left ventricular ejection fraction <50%, only the presence of LGE outside the insertion points was a significant predictor of SCD/aborted SCD (HR 10.01, 95% CI 1.21-83.86, p=0.033). The performance of the multivariable sudden cardiac death risk model was improved by the addition of LGE (++) to the traditional risk factors (likelihood ratio p=0.005). The Kaplan-Meier curves showed better event free survival in the LGE (-) and LGE (+) patient groups compared to the LGE (++) group. CONCLUSIONS: In HCM patients, presence of LGE outside interventricular insertion points is associated with increased risk of sudden cardiac death or its equivalent as well as overall mortality. Cardiac fibrosis as a substrate for SCD in HCM may be identified on CMR and serve as an imaging biomarker of increased risk. PMID- 26363821 TI - Aqueous extraction of hemicelluloses from spruce--From hot to warm. AB - Aqueous extraction of hemicelluloses from spruce sapwood was performed at 90 degrees C and 110 degrees C. One of the main goals was to study if the same reaction mechanisms are valid at low temperatures as the ones observed previously at higher temperatures. An intensified cascade reactor system with a high liquid solid ratio (~ 180) was used in the experiments. Differences between the sugar specific extraction rates were observed especially in the beginning of the extraction processes. The experimental results fitted well to a kinetic model developed at higher temperatures, which confirms that the dissolution occurs with the same mechanisms at low temperature. Moreover, the correlation of the pH with the amount of sugars dissolved concurred with previous observations. The results contradict the assumption that low temperature dissolution would not occur and they help in studying the early stages of extraction as the kinetics are considerably slowed down. PMID- 26363822 TI - Progressive deconstruction of Arundo donax Linn. to fermentable sugars by acid catalyzed ionic liquid pretreatment. AB - Acid enhanced ionic liquid (IL) 1-n-butyl-3-methylimidazolium chloride ([C4 mim]Cl) pretreatment has shown great potential for boosting the yield of sugars from biomass cost-effectively and environmental-friendly. Pretreatment with shorter processing time will promote the commercial viability. In this work, pretreatment of reduced Amberlyst catalysis time of 34 min was demonstrated to be the most effective among time-varying pretreatments, evidenced by partial removal of hemicellulose and cellulose crystal transformation of Arundo donax Linn. A higher fermentable sugar concentration of 10.42 g/L (2% substrate) was obtained after 72 h of saccharification than the others. Total processing time to reach 92% glucose yield was cut down to approximately 26 h. Progressive deconstruction of crop cell wall was occurred with increased catalysis time by gradual releasing of H3O(+) of Amberlyst. However, vast lignin re-deposited polymers on fibers could hinder further enzymatic hydrolysis. These discoveries provide new insights into a more economic pretreatment for bioethanol production. PMID- 26363823 TI - Reinitiation of Withdrawn or Modified Neuroimaging Requests After Collaborative Consultation. AB - RATIONALE AND OBJECTIVES: This study explored four common sequences of interaction between providers and a collaborative, nondenial model preauthorization program to assess the extent to which the collaborative consultation impacted care delivered to a patient in the 30 days after a neuroimaging consult. In each of the sequences examined, providers interacted with the preauthorization program's consulting radiologist and modified their imaging study requests during the interaction. If providers did not subsequently reinitiate the original study requests, then it suggests that the study resulting from the collaborative consultation fulfilled the providers' clinical objective. MATERIALS AND METHODS: Four years of retrospective authorization and clinical data were analyzed to determine the rate at which requests modified through peer to-peer consultation were reinitiated in the following four sequences: 1) request for head computed tomography (CT) modified to head magnetic resonance imaging (MRI), 2) request for both head CT and intracranial CT angiography (CTA) or both head MRI and intracranial MRA modified to a request for a single study, 3) request for both a CT of the head and sinuses modified to a request for a single study, and 4) request for an MRI of the head and orbits modified to a request for a single study. RESULTS: In three of the sequences, no provider reinitiated a study within 30 days. In the fourth sequence, only 4 of 64 (6%) withdrawn requests for head CT/MRI or head CTA/MRA were reinitiated within 30 days. CONCLUSIONS: Modifications after collaborative consultations rarely lead to repeat imaging requests, confirming the utility of the consultations. PMID- 26363824 TI - Satisfaction of Search in Chest Radiography 2015. AB - RATIONALE AND OBJECTIVES: Two decades have passed since the publication of laboratory studies of satisfaction of search (SOS) in chest radiography. Those studies were performed using film. The current investigation tests for SOS effects in computed radiography of the chest. METHODS: Sixty-four chest computed radiographs half demonstrating various "test" abnormalities were read twice by 20 radiologists, once with and once without the addition of a simulated pulmonary nodule. Receiver-operating characteristic detection accuracy and decision thresholds were analyzed to study the effects of adding the nodule on detecting the test abnormalities. Results of previous studies were reanalyzed using similar modern techniques. RESULTS: In the present study, adding nodules did not influence detection accuracy for the other abnormalities (P = .93), but did induce a reluctance to report them (P < .001). Adding nodules did not affect inspection time (P = .58) so the reluctance to report was not associated with reduced search. Reanalysis revealed a similar decision threshold shift that had not been recognized in the early studies of SOS in chest radiography (P < .01) in addition to reduced detection accuracy (P < .01). CONCLUSIONS: The nature of SOS in chest radiography has changed, but it is not clear why. ADVANCES IN KNOWLEDGE: SOS may be changing as a function of changes in radiology education and practice. PMID- 26363825 TI - Prospective study evaluating the effect of mifepristone on E-cadherin expression in villi in early pregnancy. AB - BACKGROUND: E-cadherin plays an important regulatory role in implantation, embryo development and placentation. This study aimed to determine the effect of mifepristone on E-cadherin expression in human villi in early pregnancy. STUDY DESIGN: Forty healthy women seeking elective pregnancy termination at 5-7 weeks of gestation were recruited. Of these, 22 women chose medical termination (mifepristone-treated group) and took 25mg mifepristone every 12h for 3 days and 600MUg buccal misoprostol on the morning of the fourth day. The other 18 women underwent vacuum aspiration (control group). Following collection of villi, E cadherin protein expression was assessed by immunohistochemical analysis, and E cadherin mRNA expression was assessed by reverse transcription-polymerase chain reaction. RESULTS: E-cadherin protein expression was significantly higher (p<0.05) in villous cytotrophoblast cells in the mifepristone-treated group compared with the control group. E-cadherin mRNA expression was also significantly higher (p<0.01) in the mifepristone-treated group compared with the control group. CONCLUSION: E-cadherin expression in villi may be involved in mifepristone-induced pregnancy termination. PMID- 26363826 TI - Incremental cost-effectiveness of trauma service improvements for road trauma casualties: experience of an Australian major trauma centre. AB - Objective The aim of the present study was to estimate the cost-effectiveness of trauma service funding enhancements at an inner city major trauma centre. Methods The present study was a cost-effectiveness analysis using retrospective trauma registry data of all major trauma patients (injury severity score >15) presenting after road trauma between 2001 and 2012. The primary outcome was cost per life year gained associated with the intervention period (2007-12) compared with the pre-intervention period (2001-06). Incremental costs were represented by all trauma-related funding enhancements undertaken between 2007 and 2010. Risk adjustment for years of life lost was conducted using zero-inflated negative binomial regression modelling. All costs were expressed in 2012 Australian dollar values. Results In all, 876 patients were identified during the study period. The incremental cost of trauma enhancements between 2007 and 2012 totalled $7.91million, of which $2.86million (36%) was attributable to road trauma patients. After adjustment for important covariates, the odds of in-hospital mortality reduced by around half (adjusted odds ratio (OR) 0.48; 95% confidence interval (CI) 0.27, 0.82; P=0.01). The incremental cost-effectiveness ratio was A$7600 per life year gained (95% CI A$5524, $19333). Conclusion Trauma service funding enhancements that enabled a quality improvement program at a single major trauma centre were found to be cost-effective based on current international and Australian standards. What is known about this topic? Trauma quality improvement programs have been implemented across most designated trauma hospitals in an effort to improve hospital care processes and outcomes for injured patients. These involve a combination of education and training, the use of audit and key performance indicators. What does this paper add? A trauma quality improvement program initiated at an Australian Major Trauma Centre was found to be cost effective over 12 years with respect to years of life saved in road trauma patients. What are the implications for practitioners? The results suggest that adequate resourcing of trauma centres to enable quality improvement programs may be a cost-effective measure to reduce in-hospital mortality following road trauma. PMID- 26363827 TI - Outcome of Muscle-Invasive Urothelial Bladder Cancer After Radical Cystectomy. AB - We aimed at clarification of reasons for recurrence of urothelial carcinoma after radical cystectomy in a retrospective study that included 189 patients. Presence of lymphovascular invasion even in node-negative cases, high tumor grade, and high nodal stage appeared to be independent predictors for recurrence. This raises the necessity for postoperative multimodality treatment to improve disease free survival. BACKGROUND: Radical cystectomy remains the gold standard for local control of muscle-invasive bladder cancer. Despite that, a significant proportion of patients develop disease recurrence. Several predictors for recurrence have been described and the implication of such factors on development of recurrence will help in modification of treatment strategies to improve the prognosis of bladder cancer patients. PATIENTS AND METHODS: This is a retrospective study carried on patients with muscle-invasive urothelial carcinoma who underwent radical cystectomy at the National Cancer Institute in 3 years; January 2007 to December 2009, and analyzed for the development of recurrence and potential risk factors. RESULTS: The 3-year disease-free survival (DFS) rate was 56%. Seventy patients (37%) developed disease recurrence during the follow-up period. Of these recurrences, 17 patients (24.3%) developed local and/or regional recurrences, 45 patients (64.3%) developed distant metastasis, and 8 patients (11.4%) developed local and/or regional and distant recurrences. In univariate analysis, lymph node metastasis (P < .001), lymphovascular invasion (LVI) (P < .001), high grade (P = .005), and advanced tumor stage (P = .002) were significantly associated with development of recurrence. In multivariate analysis, lymph node metastasis, LVI, and high grade were significantly associated with tumor recurrence and poor DFS. CONCLUSION: Lymph node metastasis, LVI, and high tumor grade were independent prognostic factors that affected tumor recurrence and DFS. LVI status should be reported in radical cystectomy specimens to help in risk assessment of patients especially in node-negative cases. PMID- 26363828 TI - Stroke rehabilitation: Does the therapy area provide a physical challenge? AB - It has been previously shown that stroke patients undergoing rehabilitation perform most physical activity under the supervision of a therapist when in the therapy area and very little activity when elsewhere. The aim of this paper was to identify conditions surrounding the performance of physical activity in the therapy area, in order to design strategies which would increase physical activity throughout the rehabilitation unit. Sixteen hemiplegic patients were observed in the therapy area. They were most active when with a therapist, whereas when alone, nearly two-thirds of their time was spent inactive. it appears that it is too difficult for patients to bridge the gap between fully supervised and unsupervised practice. Strategies to provide patients with semi supervised practice as a way of increasing the amount of overall physical activity, such as group sessions, are explored. PMID- 26363829 TI - Sonographic measurement of diaphragmatic displacement during tidal breathing manoeuvres - a reliability study. AB - The aim of this investigation was to establish a reliable method of measuring diaphragm movement during relaxed tidal breathing. This study follows a previous study in which test-retest reliability was established for maximal breaths but not for tidal breaths (Blaney and Sawyer 1997). Twelve normal subjects were tested in a semi-reclined long sitting position. Sonographic measurements were taken for tidal breaths during four different patterns of breathing. All breaths were controlled for inspired volume. Testing was repeated one week later under the same conditions. The results showed that the method for measuring diaphragmatic movement at tidal breathing during a given pattern of breathing was reliable. This method will allow further investigation of the diaphragm during different breathing manoeuvres at tidal volume. PMID- 26363830 TI - People living in remote communities can have best-practice diabetes care. PMID- 26363831 TI - Detection of Deep Venous Thrombosis Using a Pocket-Size Ultrasound Examination Device. PMID- 26363832 TI - Resting Aortic Valve Area at Normal Transaortic Flow Rate Reflects True Valve Area in Suspected Low-Gradient Severe Aortic Stenosis. AB - OBJECTIVES: This study sought to assess the diagnostic impact of stress echocardiography (SE) in patients with suspected low-flow, low-gradient aortic stenosis but normal resting transvalvular flow rate. BACKGROUND: SE may help to distinguish between true severe aortic stenosis and pseudosevere aortic stenosis in patients with low aortic valve area (AVA) and mean gradient. However, if rest flow rate is normal, then SE may not confer any additional diagnostic value, irrespective of resting left ventricular ejection fraction (LVEF) and indexed stroke volume (SVi). METHODS: Sixty-seven patients with suspected low-flow, low gradient aortic stenosis who underwent SE were retrospectively studied. Following stratification by rest LVEF, SVi, and flow rate-using cutoffs of 50%, 35 ml/m(2), and 200 ml/s, respectively-we tested for significant changes in AVA during SE. RESULTS: Mean age was 77 +/- 9 years and 60% of patients were male. Mean values for rest variables were as follows: AVA: 0.77 +/- 0.12 cm(2); mean gradient: 27 +/- 7 mm Hg; flow rate: 182 +/- 37 ml/s; SVi: 32 +/- 8 ml/m(2); and LVEF: 45 +/- 15%. During SE, significant increases in AVA were observed regardless of resting LVEF and SVi state. In patients with rest flow rate >=200 ml/s, AVA did not increase significantly during stress (rest AVA: 0.90 cm(2) vs. stress AVA: 0.97 cm(2); p = 0.11), and positive predictive value for confirming underlying true severe aortic stenosis was 84%. In adjusted analyses, rest flow rate was the only parameter associated with severe AS (odds ratio: 1.05, 95% confidence interval: 1.0 to 1.1; p = 0.002). CONCLUSIONS: Rest AVA measured under normal flow rate conditions is likely to reflect the true severity of AS and unlikely to change significantly with SE. Flow normalization may only be required in patients with AVA <1 cm(2) and mean gradient <40 mm Hg when the rest flow rate is <200 ml/s. PMID- 26363833 TI - Independent Impact of RV Involvement on In-Hospital Outcome of Patients With Takotsubo Syndrome. PMID- 26363835 TI - Fusiform Appearance of Myocardial Bridging Detected by OCT. PMID- 26363834 TI - Coronary Artery Axial Plaque Stress and its Relationship With Lesion Geometry: Application of Computational Fluid Dynamics to Coronary CT Angiography. AB - OBJECTIVES: The purpose of this study was to characterize the hemodynamic force acting on plaque and to investigate its relationship with lesion geometry. BACKGROUND: Coronary plaque rupture occurs when plaque stress exceeds plaque strength. METHODS: Computational fluid dynamics was applied to 114 lesions (81 patients) from coronary computed tomography angiography. The axial plaque stress (APS) was computed by extracting the axial component of hemodynamic stress acting on stenotic lesions, and the axial lesion asymmetry was assessed by the luminal radius change over length (radius gradient [RG]). Lesions were divided into upstream-dominant (upstream RG > downstream RG) and downstream-dominant lesions (upstream RG < downstream RG) according to the RG. RESULTS: Thirty-three lesions (28.9%) showed net retrograde axial plaque force. Upstream APS linearly increased as lesion severity increased, whereas downstream APS exhibited a concave function for lesion severity. There was a negative correlation (r = -0.274, p = 0.003) between APS and lesion length. The pressure gradient, computed tomography-derived fractional flow reserve (FFRCT), and wall shear stress were consistently higher in upstream segments, regardless of the lesion asymmetry. However, APS was higher in the upstream segment of upstream-dominant lesions (11,371.96 +/- 5,575.14 dyne/cm(2) vs. 6,878.14 +/- 4,319.51 dyne/cm(2), p < 0.001), and in the downstream segment of downstream-dominant lesions (7,681.12 +/- 4,556.99 dyne/cm(2) vs. 11,990.55 +/- 5,556.64 dyne/cm(2), p < 0.001). Although there were no differences in FFRCT, % diameter stenosis, and wall shear stress pattern, the distribution of APS was different between upstream- and downstream-dominant lesions. CONCLUSIONS: APS uniquely characterizes the stenotic segment and has a strong relationship with lesion geometry. Clinical application of these hemodynamic and geometric indices may be helpful to assess the future risk of plaque rupture and to determine treatment strategy for patients with coronary artery disease. (Evaluation of FFR, WSS, and TPF Using CCTA; NCT01857687). PMID- 26363836 TI - Noninvasive Prediction of Atherosclerotic Progression: The PROSPECT-MSCT Study. PMID- 26363837 TI - Nationwide Laboratory Adherence to Myocardial Perfusion Imaging Radiation Dose Reduction Practices: A Report From the Intersocietal Accreditation Commission Data Repository. AB - OBJECTIVES: This study sought to examine current laboratory practices for radiation effective doses for myocardial perfusion imaging (MPI) and laboratory adherence to guideline-directed radiation reduction practices. BACKGROUND: A recent focus on radiation dose reduction for cardiovascular imaging has led to several published guidelines and consensus statements detailing performance metrics for laboratory practices. We sought to examine laboratory adherence to optimized radiation dose protocol recommendations among 5,216 submitted cases from 1,074 MPI laboratories evaluated for Intersocietal Accreditation Commission accreditation. METHODS: Eligible imaging centers included MPI laboratories enrolled in the Intersocietal Accreditation Commission data repository of accreditation applications from 2012 to 2013. Accreditation requires submission of 3 to 5 cases for evaluation of a range of representative cases. Based on standard dosimetry for rest and stress MPI, an effective dose (in millisieverts) was calculated. Model simulations were performed to estimate guideline-directed effective doses. RESULTS: The average effective dose was 14.9 +/- 5.8 mSv (range 1.4 to 42.4 mSv). A 1-day technetium Tc 99m protocol was used in 82.9% of cases, whereas a 2-day technetium Tc 99m and dual isotope protocol was used in 7.5% of submitted cases. Only 1.5% of participating imaging centers met current guidelines for an average laboratory radiation exposure <=9 mSv, whereas 10.1% of patient effective doses were >20.0 mSv. A model simulation replacing the radiation exposure of dual isotope MPI with that of a 1-day technetium Tc 99m protocol reduced the proportion of patients receiving an effective dose >20 mSv to only 2.7% of cases (p < 0.0001). CONCLUSIONS: Mandatory laboratory accreditation for MPI allows for examination of current radiation dosimetry practices. Current guidelines for reduced patient-specific radiation exposure are rarely implemented, with few laboratories meeting recommendations of <=9 mSv for 50% of patients. Increased educational efforts and the development of performance measures for laboratory accreditation may be required to meet current radiation dose-reduction standards. PMID- 26363838 TI - Lumen Measurements From Quantitative Coronary Angiography and IVUS: A PROSPECT Substudy. PMID- 26363839 TI - Localization of Coronary High-Intensity Signals on T1-Weighted MR Imaging: Relation to Plaque Morphology and Clinical Severity of Angina Pectoris. AB - OBJECTIVES: This study sought to investigate the relationship between localization of high-intensity signals (HISs) on T1-weighted imaging (T1WI) with the noncontrast magnetic resonance technique and plaque morphology detected on optical coherence tomography, and the clinical severity of angina pectoris. BACKGROUND: Since the introduction of the T1WI noncontrast magnetic resonance technique for plaque imaging, some groups have reported that HISs in the coronary artery on T1WI are associated with a vulnerable morphology and future cardiac events. However, the association between the localization of HISs, such as coronary intrawall or intraluminal, and plaque morphology has not been investigated. METHODS: One hundred lesions with either stable or unstable angina were included and divided into 3 groups according to the following criteria using T1WI. First, the plaques with the ratio between the signal intensities of coronary plaque and cardiac muscle <=1.0 were classified as non-HISs (n = 39). Then, HISs with the ratio between the signal intensities of coronary plaque and cardiac muscle >1.0 were classified into 2 types by using cross-sectional T1WI. Those localized within the coronary wall when the lumen was identified were defined as intrawall HISs (n = 37), whereas those occupying the lumen when the lumen was not, or even if only partly, identified, were defined as intraluminal HISs (n = 24). RESULTS: Multivariate analysis revealed that intrawall HISs were associated with macrophage accumulation and the absence of calcification assessed by using optical coherence tomography. In contrast, thrombus and intimal vasculature were independent factors associated with intraluminal HISs. Furthermore, 50% of patients with intraluminal HISs experienced rest angina, such as Braunwald class II or III. CONCLUSIONS: This study shows that intrawall and intraluminal HISs on T1WI in patients with angina are related to the different types of vulnerable plaque morphology and the clinical severity. PMID- 26363841 TI - Aliikangiella marina gen. nov., sp. nov., a marine bacterium from the culture broth of Picochlorum sp. 122, and proposal of Kangiellaceae fam. nov. in the order Oceanospirillales. AB - A Gram-stain-negative, non-motile, non-spore-forming, long rod-shaped bacterium, designated strain GYP-15T, was isolated from the culture broth of a marine microalga, Picochloruma sp. 122. Phylogenetic analyses revealed that strain GYP 15T shared 90.6 % 16S rRNA gene sequence similarity with its closest relative, Kangiella aquimarina KCTC 12183T, and represents a distinct phylogenetic lineage in a robust clade consisting of GYP-15T and members of the genera Kangiella and Pleionea in the order Oceanospirillales. Chemotaxonomic and physiological characteristics, including major cellular fatty acids, NaCl tolerance and pattern of carbon source utilization, could also readily distinguish strain GYP-15T from all established genera and species. Thus, it is concluded that strain GYP-15T represents a novel species of a new genus, for which the name Aliikangiella marina gen. nov., sp. nov. is proposed. The type strain of Aliikangiella marina is GYP-15T ( = MCCC 1K01163T = KCTC 42667T). Based on phylogenetic results, 16S rRNA gene signature nucleotide pattern and some physiological characteristics, the three genera Kangiella, Pleionea and Aliikangiella are proposed to make up a novel family, Kangiellaceae fam. nov., in the order Oceanospirillales. PMID- 26363842 TI - Wagering the future: Cognitive distortions, impulsivity, delay discounting, and time perspective in adolescent gambling. AB - This study investigated the relationship of cognitive distortions, self-reported impulsivity, delay discounting, and time perspective to gambling severity in Italian adolescents. One thousand and thirty high school students were administered the South Oaks Gambling Screen Revised for Adolescents (SOGS-RA), the Gambling Related Cognitions Scale (GRCS), the Barratt Impulsiveness Scale (BIS-11), the Monetary Choice Questionnaire (MCQ), and the Consideration of Future Consequences Scale (CFC-14). A factor analysis, used to evaluate common factors assessed by the different measures, revealed a three-factor structure of Cognitive distortions, Impulsive present orientation, and Delay discounting. The results of regression analysis using factor scores showed that males scored higher than females on the SOGS-RA and that gambling severity correlated positively with high scores on the three factors. These results indicate that cognitive distortions associated with gambling are a powerful predictor of gambling severity, and that adolescent gamblers are impaired in their abilities to think about the future. PMID- 26363840 TI - Severity of Remodeling, Myocardial Viability, and Survival in Ischemic LV Dysfunction After Surgical Revascularization. AB - OBJECTIVES: This study sought to test the hypothesis that end-systolic volume (ESV), as a marker of severity of left ventricular (LV) remodeling, influences the relationship between myocardial viability and survival in patients with coronary artery disease and LV systolic dysfunction. BACKGROUND: Retrospective studies of ischemic LV dysfunction suggest that the severity of LV remodeling determines whether myocardial viability predicts improved survival with surgical compared with medical therapy, with coronary artery bypass grafting (CABG) only benefitting patients with viable myocardium who have smaller ESV. However, this has not been tested prospectively. METHODS: Interactions of end-systolic volume index (ESVI), myocardial viability, and treatment with respect to survival were assessed in patients in the prospective randomized STICH (Comparison of Surgical and Medical Treatment for Congestive Heart Failure and Coronary Artery Disease) trial of CABG versus medical therapy who underwent viability assessment (n = 601; age 61 +/- 9 years; ejection fraction <=35%), with a median follow-up of 5.1 years. Median ESVI was 84 ml/m(2). Viability was assessed by single-photon emission computed tomography or dobutamine echocardiography using pre-specified criteria. RESULTS: Mortality was highest among patients with larger ESVI and nonviability (p < 0.001), but no interaction was observed between ESVI, viability status, and treatment assignment (p = 0.491). Specifically, the effect of CABG versus medical therapy in patients with viable myocardium and ESVI <=84 ml/m(2) (hazard ratio [HR]: 0.85; 95% confidence interval [CI]: 0.56 to 1.29) was no different than in patients with viability and ESVI >84 ml/m(2) (HR: 0.87; 95% CI: 0.57 to 1.31). Other ESVI thresholds yielded similar results, including ESVI <=60 ml/m(2) (HR: 0.87; 95% CI: 0.44 to 1.74). ESVI and viability assessed as continuous rather than dichotomous variables yielded similar results (p = 0.562). CONCLUSIONS: Among patients with ischemic cardiomyopathy, those with greater LV ESVI and no substantial viability had worse prognosis. However, the effect of CABG relative to medical therapy was not differentially influenced by the combination of these 2 factors. Lower ESVI did not identify patients in whom myocardial viability predicted better outcome with CABG relative to medical therapy. (Comparison of Surgical and Medical Treatment for Congestive Heart Failure and Coronary Artery Disease [STICH]; NCT00023595). PMID- 26363843 TI - Long-term Outcomes of Patients with Acute Myocardial Infarction Presenting to Regional and Remote Hospitals. AB - BACKGROUND: Acute myocardial infarction (AMI) has poorer outcomes in disadvantaged populations such as those in regional and remote locations. We compared long-term outcomes associated with presentation to regional or remote hospitals among AMI patients. METHODS AND RESULTS: Administrative claims data from New South Wales (27% regional and remote residents) was used to identify patients >18 years admitted to any NSW hospital with a principal diagnosis of AMI (ICD10 codes: I21.0-I21.4) between 01/07/2004 and 30/06/2008. Hospital of presentation location with a population of <250,000 was defined as regional and remote while hospitals with a population >250,000 were deemed urban. Receipt of revascularisation and mortality were analysed and adjusted for age, comorbidities and previous revascularisation. Patients were censored at death or end of the follow-up period (31 December 2009). 39,798 patients were identified with 9,393 (23.6%) regional and remote presenters. In multivariable models, regional and remote presentation was associated with reduced rates of revascularisation (OR 0.30 95%CI 0.28-0.32; p<0.001), no impact on overall mortality (HR 1.04 95%CI 0.99-1.02; p=0.11), but with increased mortality for patients presenting with STEMI (HR 1.14; 95% CI 1.06-1.23; p<0.001). The propensity analysis was consistent with these findings. CONCLUSIONS: Presentation to a regional and remote hospital was associated with lower revascularisation rates following AMI, but with a higher long-term mortality if presenting with ST segment elevation. PMID- 26363844 TI - 3D harmonic phase tracking with anatomical regularization. AB - This paper presents a novel algorithm that extends HARP to handle 3D tagged MRI images. HARP results were regularized by an original regularization framework defined in an anatomical space of coordinates. In the meantime, myocardium incompressibility was integrated in order to correct the radial strain which is reported to be more challenging to recover. Both the tracking and regularization of LV displacements were done on a volumetric mesh to be computationally efficient. Also, a window-weighted regression method was extended to cardiac motion tracking which helps maintain a low complexity even at finer scales. On healthy volunteers, the tracking accuracy was found to be as accurate as the best candidates of a recent benchmark. Strain accuracy was evaluated on synthetic data, showing low bias and strain errors under 5% (excluding outliers) for longitudinal and circumferential strains, while the second and third quartiles of the radial strain errors are in the (-5%,5%) range. In clinical data, strain dispersion was shown to correlate with the extent of transmural fibrosis. Also, reduced deformation values were found inside infarcted segments. PMID- 26363845 TI - Multi-atlas learner fusion: An efficient segmentation approach for large-scale data. AB - We propose multi-atlas learner fusion (MLF), a framework for rapidly and accurately replicating the highly accurate, yet computationally expensive, multi atlas segmentation framework based on fusing local learners. In the largest whole brain multi-atlas study yet reported, multi-atlas segmentations are estimated for a training set of 3464 MR brain images. Using these multi-atlas estimates we (1) estimate a low-dimensional representation for selecting locally appropriate example images, and (2) build AdaBoost learners that map a weak initial segmentation to the multi-atlas segmentation result. Thus, to segment a new target image we project the image into the low-dimensional space, construct a weak initial segmentation, and fuse the trained, locally selected, learners. The MLF framework cuts the runtime on a modern computer from 36 h down to 3-8 min - a 270* speedup - by completely bypassing the need for deformable atlas-target registrations. Additionally, we (1) describe a technique for optimizing the weak initial segmentation and the AdaBoost learning parameters, (2) quantify the ability to replicate the multi-atlas result with mean accuracies approaching the multi-atlas intra-subject reproducibility on a testing set of 380 images, (3) demonstrate significant increases in the reproducibility of intra-subject segmentations when compared to a state-of-the-art multi-atlas framework on a separate reproducibility dataset, (4) show that under the MLF framework the large scale data model significantly improve the segmentation over the small-scale model under the MLF framework, and (5) indicate that the MLF framework has comparable performance as state-of-the-art multi-atlas segmentation algorithms without using non-local information. PMID- 26363846 TI - Attaining genetic height potential: Analysis of height outcomes from the ANSWER Program in children treated with growth hormone over 5 years. AB - OBJECTIVE: This study aimed to assess attainment of genetic height potential after long-term growth hormone (GH) treatment in GH-naive children diagnosed with isolated growth hormone deficiency (IGHD), multiple pituitary hormone deficiency (MPHD), born small for gestational age (SGA), or idiopathic short stature (ISS) enrolled in the American Norditropin(r) STUDIES: Web-enabled Research (ANSWER) Program. DESIGN: Children with IGHD (n=2884), MPHD (n=200), SGA (n=481), or ISS (n=733) with baseline height standard deviation score (HSDS)<=-2 were assessed over 5 years of GH treatment for mean HSDS, change in HSDS (DeltaHSDS), and corrected HSDS (HSDS-target HSDS). RESULTS: Mean HSDS and corrected HSDS significantly increased to close to target height across all diagnostic groups after 5 years of GH treatment (P<0.0001). ?HSDS at year 5 increased for all groups (IGHD: 1.8; MPHD: 2.1; SGA: 1.8; ISS: 1.6). Among patients who continued GH for 5 years, mean insulin-like growth factor-I (IGF-I) SDS increased to within normal range across all groups. Body mass index (BMI) SDS remained relatively stable in all diagnostic groups. Bone age (BA) increased, and the mean BA to chronological age (BA/CA) ratio reached or approached 1 across diagnostic groups over 5 years of GH treatment. CONCLUSIONS: Long-term GH therapy resulted in a significant increase in mean HSDS and corrected HSDS from baseline values in all diagnostic groups. The observed increase in mean corrected HSDS is consistent with growth that approached the patients' genetic height potential, although complete height gains will be evaluated at the attainment of final height. PMID- 26363848 TI - Approach to the Patient With a Negative Anion Gap. AB - When anion gap calculation generates a very small or negative number, an explanation must be sought. Sporadic (nonreproducible) measurement errors and systematic (reproducible) laboratory errors must be considered. If an error is ruled out, 2 general possibilities exist. A true anion gap reduction can be generated by either reduced concentrations of unmeasured anions such as albumin or increased concentrations of unmeasured cations such as magnesium, calcium, or lithium. This teaching case describes a patient with aspirin (salicylate) poisoning whose anion gap was markedly reduced (-47 mEq/L). The discussion systematically reviews the possibilities and provides the explanation for this unusual laboratory result. PMID- 26363847 TI - The Pharmacokinetics of Intradialytic Administration of Eculizumab in an Infant. PMID- 26363849 TI - Performance of GFR Estimating Equations Stratified by Measured or Estimated GFR: Implications for Interpretation. PMID- 26363850 TI - Human nails metabolite analysis: A rapid and simple method for quantification of uric acid in human fingernail by high-performance liquid chromatography with UV detection. AB - A rapid and simple analytical method for the quantification of uric acid (UA) in human fingernails by high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection is described. UA was extracted from human fingernail samples at 90 degrees C for 20min, then separated on an Inertsil ODS-2 column (250*4.6mm I.D., 5.0MUm, GL Sciences) by isocratic elution using methanol: 74mM phosphate buffer (pH 2.2) 2:98 (v/v). An UV detector was used to monitor at 284nm. The results indicated that under optimized measurement conditions results were achieved within 8.0min, and a good linearity was achieved from the calibration curves (r(2)>0.9999) in the range of 1.0-10000ng; the limit of detection (S/N=3) was 2.0pg, the inter-day and intra-day assay precisions were all less than 0.46% and the mean recoveries (%) of the uric acid spiked in the human fingernail were 101.95%. The amounts of UA in the fingernails of healthy volunteers were determined. PMID- 26363851 TI - Development of analytical method for simultaneous determination of five rodent unique bile acids in rat plasma using ultra-performance liquid chromatography coupled with time-of-flight mass spectrometry. AB - Bile acids (BAs) are crucial for the diagnosis, follow-up, and prognostics of liver injuries and other BA metabolism related diseases. In particular, rodent unique BAs, alpha-muricholic acid (alpha-MCA), beta-MCA, omega-MCA, tauro-alpha MCA (alpha-TMCA), and beta-TMCA, are valuable biomarkers for preclinical drug development. To the best of our knowledge, however, a simple, selective, sensitive, and robust analytical method for omega-MCA and taurine-conjugated MCAs has never been reported. We have developed a simple, selective, and sensitive analytical method for measurement of 16 BAs including the five rodent unique BAs in rat plasma using an ultra-performance liquid chromatography time-of-flight mass spectrometry (UPLC-TOF-MS) method. Activated charcoal was utilized to prepare BA-free plasma, which served as the surrogate matrix for the preparation of calibration standards and quality control (QC) samples. Results of matrix effects evaluation suggested that the BA-free plasma could be adequate as a surrogate matrix for BAs determination. Three stable isotope labelled internal standards were separated by reverse phase UPLC using gradient elution and were detected by TOF-MS in negative ion mode. The calibration curve was linear for all BAs over a range of 10-25ng/mL to 1000-10,000ng/mL, with overall imprecision below 15% and 20% at lower limit of quantification (LLOQ), respectively. This analytical method was used to determine BA concentrations in more than 300 plasma samples from rats with liver injuries induced using alpha-naphthylisocyanate, carbon tetrachloride, or flutamide. The alteration of BA concentrations was most evident for necrosis, and cholestasis hepatotoxins, with more subtle effects by steatosis and idiosyncratic hepatotoxins. In conclusion, we have developed a simple, selective, and sensitive analytical method to measure plasma 16 BAs including 5 rodent unique BAs, alpha-MCA, beta-MCA, omega-MCA, alpha-TMCA, and beta-TMCA. Our data suggested that alpha-TMCA and beta-TMCA could be useful for identification or prediction of liver injuries, a currently unmet need in preclinical toxicity. Our method using TOF-MS is useful to determine BAs in rat plasma and of use in structural analyses of metabolites in early stage of drug development. PMID- 26363852 TI - Effects of footshocks on anxiety-like behavior and mRNA levels of precursor peptides for corticotropin releasing factor and opioids in the forebrain of the rat. AB - Corticotropin releasing factor (CRF) and dynorphin are neuropeptides that are associated with the negative emotional states. Experimental evidence indicates that dynorphin neurons located in the nucleus accumbens and CRF neurons in the bed nucleus of the stria terminalis (BST) and the central nucleus of the amygdala (CeA) mediate anxiety-like behaviors immediately after the stressful experience (24-48h). The present study was done to evaluate if changes in the levels of the mRNA for these peptides in the striatum, BST, and CeA were associated with the long-lasting avoidance of novelty, a measure of an anxiety-like state, in a subset of rats exposed to unpredictable and moderately intense footshocks (5*2s of 1.5mA). Shocked rats with enhanced fear to a novel tone 24h after the footshocks (high responders; HR) displayed long-lasting avoidance in the elevated T-maze whereas shocked rats with low levels of acute fear (low responders; LR) had low levels of avoidance similar to nonshocked rats. An increase in the level of proCRF mRNA was detected in the CeA of the HR compared to LR and nonshocked rats but not in other areas of the brain sampled. In contrast, prodynorphin and proenkephalin mRNA levels in the striatum, BST and CeA were not different between HR, LR and nonshocked rats. This study provides evidence that CRF neurons in the CeA may play a role in the anxiety-like state produced in a subset of rats exposed to footshocks. PMID- 26363854 TI - [Fetal programming of chronic diseases: Current concepts and epigenetics]. PMID- 26363853 TI - PGC-1alpha controls mitochondrial biogenesis and dynamics in lead-induced neurotoxicity. AB - Due to its role in regulation of mitochondrial function, PGC1alpha is emerging as an important player in ageing and neurodegenerative disorders. PGC1alpha exerts its neuroprotective effects by promoting mitochondrial biogenesis (MB) and functioning. However, the precise regulatory role of PGC1alpha in the control of mitochondrial dynamics (MD) and neurotoxicity is still unknown. Here we elucidate the role of PGC1alphain vitro and in vivo in the regulatory context of MB and MD in response to lead (II) acetate as a relevant model of neurotoxicity. We show that there is an adaptive response (AR) to lead, orchestrated by the BAP31 calcium signalling system operating between the ER and mitochondria. We find that this hormetic response is controlled by a cell-tolerated increase of PGC1alpha expression, which in turn induces a balanced expression of fusion/fission genes by binding to their promoters and implying its direct role in regulation of MD. However, dysregulation of PGC1alpha expression through either stable downregulation or overexpression, renders cells more susceptible to lead insult leading to mitochondrial fragmentation and cell death. Our data provide novel evidence that PGC1alpha expression is a key regulator of MD and the maintenance of tolerated PGC1alpha expression may offer a promising strategy for neuroprotective therapies. PMID- 26363855 TI - [Child health environment in the context of relocating of camp site families to social housing]. AB - INTRODUCTION: Housing interventions aimed at overcoming poverty can lead to changes in the health status of children by modifying risk factors in their physical and social environment OBJECTIVE: the aim was to identify children's environmental health factors to change with the relocation of families from slums to public housing. SUBJECTS AND METHOD: A cross-sectional study was conducted in children ages 2-8 years old of families relocated to public housing (n=115) who were compared to children residing in slums (n=88) in Santiago, Chile. Family socioeconomic characteristics, indoor environment and neighborhoods were collected. It was included respiratory symptoms, accidents and maternal-child care of children. chi2, Fisher and Mann-Whitney test were used to compare groups. RESULTS: There were differences in households related to pets keeping, presence of humidity/molds in homes, types of fuels, and perceived safety problems in neighborhoods (p<0.05). The families from slums reported higher tenancy of pets (73.8% v/s 32.2%%), humidity/molds in homes (43.,2% v/s 18.3%), use of wood for heating (39.8% v/s 0.0%), compared with families of public housing. Residents of public housing perceived more safety problems in neighborhood, and children have more asthma related symptoms and have lower diversity of accidents in home. CONCLUSION: Among the factors studied, indoor air quality and safety in neighborhoods could be linked to changes from the relocation of families. This reinforces the need to deepen the positive and negative influences of residential mobility of these groups focused on child welfare perspective. PMID- 26363856 TI - [Sociodemographic and clinical characteristic of the population attended in the Instituto Teleton de Santiago]. AB - The Institutos Teleton care for 85% of the Chilean child population with neuromusculoskeletal disability, the large percentage concentrating in this population. However, there are no registers that enable a profile to be determined on this population. OBJECTIVE: To determine the profile of patients attending the Instituto Teleton de Santiago during the year 2012. PATIENTS AND METHOD: The sociodemographic characteristics were analyzed from the computerised records of the Instituto Teleton de Santiago on active patients who were seen during the year 2012. RESULTS: A total of 8,959 patients were seen during the study year in the Instituto Teleton de Santiago. As regards socioeconomic level, 33.3% were in extreme poverty, 28.7% to low-middle level. The main clinical diagnoses were cerebral palsy and other encephalopathies that also lead to motor disability, and accounted for 55.4% of the cases. CONCLUSIONS: As a result of determining this profile, it would be appropriate to encourage the need for a national register of the child population with disability, as well as their particular characteristics in order to make decisions on public policy, as a destination for funds or support programs. PMID- 26363857 TI - [Incidence of admissions due to pneumonia in children under 24 months old before and after the introduction of the 10-valent pneumococcal conjugate vaccine into the National Immunization Program of Chile]. AB - INTRODUCTION: Streptococcus pneumoniae is the leading cause of bacterial pneumonia in children, especially in the hospitalized population. The 10-valent pneumococcal vaccine was included in the National Immunization Program of Chile in 2011. This study aims to evaluate the incidence of pneumonia in hospitalized children<24 months of age in the Luis Calvo Mackenna Hospital before and after the introduction of the pneumococcal vaccine into the National Immunization Program. PATIENTS AND METHODS: Passive surveillance study. Patients<24 months with discharge diagnosis of bacterial pneumonia from Luis Calvo Mackenna Hospital were studied between 2009 and 2013. Data were obtained from the Luis Calvo Mackenna Hospital's Statistical Service. The incidence of pneumonia was evaluated in the pre-vaccination period (2009-2010) and in the post-vaccination period (2012-2013). RESULTS: During the study period, an average of 4,321 discharges/year was observed in children<24 months (range: 3,587-4,702), with a significant decrease from pre- to post-vaccination vaccine period (4,644 vs 4,013, P<.001). The average incidence of pneumonia ranged from 3.4/100,000 to 1.5/100,000 in the pre- and post-vaccine period, respectively (P=.009), with an annual mean of 157 cases of pneumonia in the pre- vaccine period, and 62 cases in the postvaccine period (P<.001) and a decrease in incidence between the two periods of 56%. CONCLUSION: This study confirms information previously obtained in other countries, which show a decrease in the incidence of pneumonia associated with the implementation of a pneumococcal vaccine at the population level. Ongoing surveillance is required to evaluate if this effect is maintained over time and expands to older populations. PMID- 26363858 TI - [High flow nasal cannula in infants: Experience in a critical patient unit]. AB - INTRODUCTION: The high flow nasal cannula (HFNC) is a method of respiratory support that is increasingly being used in paediatrics due to its results and safety. OBJECTIVE: To determine the efficacy of HFNC, as well as to evaluate the factors related to its failure and complications associated with its use in infants. PATIENTS AND METHOD: An analysis was performed on the demographic, clinical, blood gas, and radiological data, as well as the complications of patients connected to a HFNC in a critical care unit between June 2012 and September 2014. A comparison was made between the patients who failed and those who responded to HFNC. A failure was considered as the need for further respiratory support during the first 48hours of connection. The Kolmogorov Smirnov, Mann-Whitney U, chi squared and the Exact Fisher test were used, as well as correlations and a binary logistic regression model for P<=.05. RESULTS: The study included 109 patients, with a median age and weight: 1 month (0.2-20 months) and 3.7kg (2-10kg); 95 percentile: 3.7 months and 5.7kg, respectively. The most frequent diagnosis and radiological pattern was bronchiolitis (53.2%) and interstitial infiltration (56%). Around 70.6% responded. There was a significant difference between failure and response in the diagnosis (P=.013), radiography (P=018), connection context (P<.0001), pCO2 (median 40.7mmHg [15.4-67 mmHg] versus 47.3mmHg [28.6-71.3mmHg], P=.004) and hours on HFNC (median 60.75hrs [5-621.5 hrs] versus 10.5hrs [1-29 hrs], P<.0001). The OR of the PCO2 >= 55mmHg for failure was 2.97 (95% CI; 1.08-8.17; P=.035). No patient died and no complications were recorded. CONCLUSION: The percentage success observed was similar to that published. In this sample, the failure of HFNC was only associated with an initial pCO2 >= 55mmHg. On there being no complications reported as regards it use, it is considered safe, although a randomised, controlled, multicentre study is required to compare and contrast these results. PMID- 26363859 TI - [Severe vitamin D deficiency in children from Punta Arenas, Chile: Influence of nutritional status on the response to supplementation]. AB - There is a high risk of vitamin D (VD) deficiency in the population of southern Chile that can be treated with VD supplements. Weight excess (WE) can influence the response to supplements. OBJECTIVES: To study the prevalence of VD deficiency and the effect of cholecalciferol (VD3) supplements in healthy children from Punta Arenas, Chile, and evaluate a possible association with nutritional status. METHODOLOGY: Demographic and anthropometric data, as well as laboratory assessment of serum 25-hidroxyvitamin D (25OHD) and other bone metabolism parameters were evaluated. After baseline evaluation, children were supplemented with VD3 1600 IU/day for one month, after which 25OHD was retested. RESULTS: Of the 108 children studied, 50% were boys, and had a mean age of 9.6+/-0.5 years. Nutritional assessment showed that 39% had normal weight, 46% were overweight, and 15% were obese. Median 25OHD was 10.9ng/ml: 96.3% had deficiency (<20ng/ml) and 3.7% insufficiency (20-29ng/ml). Severe deficiency was found in 62% (<12ng/ml). Baseline 25OHD was not affected by nutritional status. After supplementation, median 25OHD was 17.5ng/ml: 62% had deficiency, 36% insufficiency, and 2% sufficiency (>30ng/ml). Children with WE had a significantly lower increase in 25OHD than children with normal weight (5+/-5.5 vs. 7.7+/-4.9, p=03). Children with WE may require 32% higher VD dose than normal weight children to attain the same 25OHD concentration. CONCLUSIONS: Chilean schoolchildren from Punta Arenas have high prevalence of WE and VD deficiency, with a majority in the range of severe VD deficiency. WE interferes in the response to VD supplementation, leading to a lower increase in 25OHD. PMID- 26363860 TI - [Ingestion of caustic substances in children: 3 years of experience]. AB - INTRODUCTION: There is no clear consensus on the management of accidental ingestion of caustic substances in paediatrics. The aim of this study was to determine the profile of the paediatric population treated due to caustic ingestion in a Healthcare Centre. PATIENTS AND METHOD: A descriptive study was conducted on patients treated for the ingestion of caustic substances in our hospital during the period 2008-2011. RESULTS: A total of 12 patients were treated, with a mean age of 3.8 years (1-13 years), with the majority males (58.8%). An alkaline product was ingested by 58.3%, and an acid by 41.6%. The majority (58.3%) did not refer to symptoms and the remainder referred to vomiting (33.3%), odynophagia (16.6%), haematemesis (8.3%), hyper-salivation (8.3%) and shortness of breath (8.3%). Oral cavity lesions were observed in 75% of cases. All, except one, were accidental. An endoscopy was performed on all of them (100%) between 12 and 24hours post-ingestion, with pathological findings in 41.6%. In the group that ingested an alkali, 2 (16.6%) patients had lesions, one a grade 2B and one a grade 3 oesophagitis. In the acid ingestion group, 4 (33.3%) patients had lesions; one grade 1-2A oesophagitis, two acute non-erosive gastritis, and one acute haemorrhagic gastritis. A follow-up endoscopy was performed depending on the previous endoscopic findings. Only two patients presented with complications. CONCLUSIONS: Emphasis is placed on the endoscopic evaluation in the first 24hours of deliberate asymptomatic ingestions, as well as a strict follow-up in those that ingested acids, due to delayed associated lesions. PMID- 26363861 TI - [Pediatric intervertebral disc calcification: A rare cause of acquired torticollis. Case report]. AB - INTRODUCTION: Pain and cervical muscle spasm are common reasons why parents bring children to the pediatric emergency department. The first steps are the gathering of medical history of the patient and a physical examination. If musculoskeletal damage is suspected, cervical spine x-rays should be obtained. An intervertebral disc calcification finding, in the absence of other radiological lesions should suggest pediatric intervertebral disc calcification. OBJECTIVE: To present a case of intervertebral disc calcification, a rare condition that must be considered in the differential diagnosis of torticollis and neck pain in childhood. CASE REPORT: A seven-year-old male patient without morbid history and no history of trauma or rough sport practice. He consulted the emergency room for pain and cervical contracture for the last six days. C reactive protein and red cell sedimentatio rates were slightly elevated. Imaging studies showed calcification of the C5-C6 intrvertebral disc and anterior disc protrusion. The patient was hospitalized for evaluation and pain management, with good clinical response and continue afterwards with non-steroidal anti-inflammatory drugs and a soft collar. At the 6-month-follow up, the patient had resolved symptoms and calcifications. CONCLUSIONS: Pediatric intervertebral disc calcification is a rare cause of acquired torticollis, with a benign and self-limited outcome. Conservative management, as well as clinical and imaging follow-up is recommended. PMID- 26363862 TI - [Use of inflammatory markers for monitoring paediatric asthma]. AB - The assessment of asthma control takes into account the symptoms, quality of life, lung function, and inflammatory markers. In the last few years, there has been a large increase in the number of publications related to the study of biomarkers in the management of paediatric asthma. Despite the large variety of inflammatory markers described in research studies, only a small group has shown to be useful in monitoring the disease. Induced sputum eosinophils offer the most solid evidence in assessing asthma control. Exhaled breath condensate and urinary leucotrienes could be useful in the future if there is standardisation in their procedures and interpretation of the results. Nitric oxide, basic eosinophil cationic protein, and bronchial biopsy with bronchoalveolar lavage, only appeared to be useful in a reduced group of patients. PMID- 26363863 TI - [What should the paediatrician know about hyperphenylalaninaemia?]. AB - Hyperphenylalaninaemias are defined by a blood phenylalanine over 2mg/dl. The main cause is due to a mutation in the gene that codes the phenylalanine hydroxylase that catalyses the reaction that converts phenylalanine into tyrosine. The hyperphenylalaninaemias are classified into benign or mild hyperphenylalaninaemias, or mild, moderate or classic phenylketonurias. Due to its delayed detection outside the neonatal period it causes severe mental retardation. Its detection along with congenital hypothyroidism has been part of the National Neonatal Screening Program since 1992 in Chile. This article aims to answer the most common questions asked by the paediatrician when faced with a patient with hyperphenylalaninaemias. PMID- 26363864 TI - Reverse Epidemiology of Traditional Cardiovascular Risk Factors in the Geriatric Population. AB - Traditional risk factors of cardiovascular death in the general population, including body mass index (BMI), serum cholesterol, and blood pressure (BP), are also found to relate to outcomes in the geriatric population, but in an opposite direction. Some degrees of elevated BMI, serum cholesterols, and BP are reportedly associated with lower, instead of higher, risk of death among the elderly. This phenomenon is termed "reverse epidemiology" or "risk factor paradox" (such as obesity paradox) and is also observed in a variety of chronic disease states such as end-stage renal disease requiring dialysis, chronic heart failure, rheumatoid arthritis, and AIDS. Several possible causes are hypothesized to explain this risk factor reversal: competing short-term and long-term killers, improved hemodynamic stability in the obese, adipokine protection against tumor necrosis factor-alpha, lipoprotein protection against endotoxins, and lipophilic toxin sequestration by the adipose tissue. It is possible that the current thresholds for intervention and goal levels for such traditional risk factors as BMI, serum cholesterol, and BP derived based on younger populations do not apply to the elderly, and that new levels for such risk factors should be developed for the elderly population. Reverse epidemiology of conventional cardiovascular risk factors may have a bearing on the management of the geriatric population, thus it deserves further attention. PMID- 26363865 TI - Three-Dimensional Evaluation of Implant Positioning in the Maxillary Sinus Septum: A Retrospective Study. AB - BACKGROUND: The aim of this study was to simulate implant placement in the maxillary sinus septum, as a potential alternative site to avoid sinus grafting. MATERIAL AND METHODS: One hundred partially or completely edentulous patients, with their maxillary sinus septum present in the edentulous region, were selected from the database of the Department of Maxillofacial Surgery, Cliniques Universitaires Saint Luc, Bruxelles, Belgium. Three-dimensional (3D) reconstructions were created using 3D planning software. 3D reconstructions were performed for each maxillary sinus. Using the software implant library, the implants that presented the best fit with the maxillary sinus septum and that followed the established inclusion criteria were selected. RESULTS: All of the implants were inserted in premolar and molar regions. Most implants were inserted in the position of the second molar (21 of 55) or in the position of the first molar (17 of 55). In all sites the most frequently used implant was 4 mm in diameter and 7 mm in height. The mean coronal angle for the implant was 80.19+/ 17.13 degrees and the mean sagittal angle was 94.83+/-9.94 degrees. The septal height represents 38.13% of the total available bone height (ABH). The mean percentage of the septum used to insert the implants was 47.33+/-2.47%. The septum increased the available bone height by a mean value of 2.18+/-1.47 mm. In 45 cases, the septa did not permit implant placement. CONCLUSIONS: In completely edentulous patients, inserting implants in sinus septa does not exclude the need for sinus grafting, but in partially edentulous patients, this minimally invasive technique is an alternative to subantral augmentation. PMID- 26363866 TI - New multifunctional melatonin-derived benzylpyridinium bromides with potent cholinergic, antioxidant, and neuroprotective properties as innovative drugs for Alzheimer's disease. AB - A novel series of melatonin-derived benzylpyridinium bromides have been designed, synthesized, and evaluated as multi-functional anti-AD agents with cholinesterase inhibitory, antioxidant, and neuroprotective activities. In vitro studies showed that most of these compounds exhibited potent inhibitory activity toward h-AChE and h-BuChE, and good antioxidant capacity in the ORAC assay. In particular, compound 19 was the most attractive derivative, showing the highest potency to inhibit ChEs (AChE: IC50 = 0.11 MUM; BuChE: IC50 = 1.1 MUM) and good antioxidant ability (ORAC (trolox) = 3.41). Kinetic and molecular modeling studies indicated that 19 was a mixed-type inhibitor, binding simultaneously to active and peripheral sites of AChE. Moreover, 19 also showed good neuroprotective effects in human SH-SY5Y neuroblastoma cells. Taken together, these results suggested that compound 19 might be a promising multi-target drug candidate worthy of further pursuit. PMID- 26363867 TI - Delta(5)-Cholenoyl-amino acids as selective and orally available antagonists of the Eph-ephrin system. AB - The Eph receptor-ephrin system is an emerging target for the development of novel anti-angiogenic therapies. Research programs aimed at developing small-molecule antagonists of the Eph receptors are still in their initial stage as available compounds suffer from pharmacological drawbacks, limiting their application in vitro and in vivo. In the present work, we report the design, synthesis and evaluation of structure-activity relationships of a class of Delta(5)-cholenoyl amino acid conjugates as Eph-ephrin antagonists. As a major achievement of our exploration, we identified N-(3beta-hydroxy-Delta(5)-cholen-24-oyl)-L-tryptophan (UniPR1331) as the first small molecule antagonist of the Eph-ephrin system effective as an anti-angiogenic agent in endothelial cells, bioavailable in mice by the oral route and devoid of biological activity on G protein-coupled and nuclear receptors targeted by bile acid derivatives. PMID- 26363869 TI - Design, synthesis and biological evaluation of novel 1,2,4-triazolo [3,4 b][1,3,4] thiadiazines bearing furan and thiophene nucleus. AB - Twenty-six novel 1,2,4-triazolo [3,4-b][1,3,4] thiadiazines containing furan and thiophene nucleus were designed, synthesized and evaluated for their antiproliferative activities. The results indicated that most of the compounds showed moderate to potent antiproliferative activities against four cancer cell lines, PC-3, HepG2, A549, and MCF-7. Particularly, compound 32 showed eleven-, three-, and two-fold improvement compared to positive control fluorouracil in inhibiting HepG2, PC-3, and A549 cell proliferation with IC50 values of 5.09, 3.70 and 12.74 MUM, respectively. Further flow-activated cell sorting analysis revealed that the most promising compound 32 displayed a significant effect on G2/M cell-cycle arrest in a dose-dependent manner in PC-3 cells. These encouraging results should provide important information for the development of new anticancer agents. PMID- 26363868 TI - 3-Nitrotriazole-based piperazides as potent antitrypanosomal agents. AB - Novel linear 3-nitro-1H-1,2,4-triazole-based piperazides were synthesized and evaluated as antitrypanosomal agents. In addition, some bisarylpiperazine ethanones which were formed as by-products were also screened for antiparasitic activity. Most 3-nitrotriazole-based derivatives were potent and selective against Trypanosoma cruzi parasites, but only one displayed these desired properties against Trypanosoma brucei rhodesiense. Moreover, two 3-nitrotriazole based chlorophenylpiperazides were moderately and selectively active against Leishmania donovani. Although the bisarylpiperazine-ethanones were active or moderately active against T. cruzi, none of them demonstrated an acceptable selectivity. In general, 3-nitrotriazole-based piperazides were less toxic to host L6 cells than the previously evaluated 3-nitrotriazole-based piperazines and seven of 13 were 1.54- to 31.2-fold more potent antichagasic agents than the reference drug benznidazole. Selected compounds showed good ADMET characteristics. One potent in vitro antichagasic compound (3) was tested in an acute murine model and demonstrated antichagasic activity after a 10-day treatment of 15 mg/kg/day. However, neither compound 3 nor benznidazole showed a statistically significant P value compared to control due to high variability in parasite burden among the untreated animals. Working as prodrugs, 3-nitrotriazole based piperazides were excellent substrates of trypanosomal type I nitroreductases and constitute a novel class of potentially effective and more affordable antitrypanosomal agents. PMID- 26363871 TI - Discovery of WQ-3810: Design, synthesis, and evaluation of 7-(3 alkylaminoazetidin-1-yl)fluoro-quinolones as orally active antibacterial agents. AB - Novel 7-(3-alkylaminoazetidin-1-yl)fluoroquinolones were designed, synthesized, and evaluated for their antibacterial activities and oral absorption rates. Against Gram-negative bacteria, 10a-e, which have various alkyl groups containing different numbers of carbon atoms (C0-C3) at the C-7 alkylaminoazetidine position, showed potent and similar antibacterial activities, whereas the activity of 10f (C4, t-Bu) was significantly lower than those of 10a-e. Conversely, the oral absorption rates of 10a-e in rats increased depending on the number of carbon atoms in the alkyl groups; 10d (C3, n-Pr) and 10e (C3, i-Pr) had high oral absorption rates (>90% at 10 mg/kg). These results demonstrated that the introduction of alkyl groups onto C-7 aminoazetidine is useful for the improvement of the oral absorption rates of these drugs while maintaining their antibacterial activities. As a conclusion, from this series of fluoroquinolones, WQ-3810 (10e), having 3-isopropylaminoazetidine as the C-7 substituent, was identified as an orally active antibacterial agent with a potent in vitro activity. PMID- 26363870 TI - Synthesis and evaluation of 1-hydroxy/methoxy-4-methyl-2-phenyl-1H-imidazole-5 carboxylic acid derivatives as non-purine xanthine oxidase inhibitors. AB - Xanthine oxidase is a key enzyme that catalyses hypoxanthine and xanthine to uric acid, whose overproduction leads to the gout-causing hyperuricemia. In this study, a series of 1-hydroxy/methoxy-4-methyl-2-phenyl-1H-imidazole-5-carboxylic acid derivatives (4a-4k and 6a-6k) was synthesized and evaluated for their inhibitory potency against xanthine oxidase. The 1-hydroxyl substituted derivatives 4a-4k showed excellent inhibitory potency with IC50 values ranging from 0.003 MUM to 1.2 MUM, with compounds 4d (IC50 = 0.003 MUM), 4e (IC50 = 0.003 MUM), and 4f (IC50 = 0.006 MUM) manifesting the most potent xanthine oxidase inhibitory potency that were comparable with that of Febuxostat (IC50 = 0.01 MUM). Lineweaver-Burk plot analysis revealed that representative compound 4f acted as a mixed-type inhibitor for xanthine oxidase. The basis of significant inhibition of xanthine oxidase by 4f was rationalized by its molecular docking into the active site of xanthine dehydrogenase. PMID- 26363872 TI - Synthesis and structure-activity relationship study of benzofuran-based chalconoids bearing benzylpyridinium moiety as potent acetylcholinesterase inhibitors. AB - A series of benzofuran-based chalconoids 6a-v were designed and synthesized as new potential AChE inhibitors. The in vitro assay of synthesized compounds 6a-v showed that most compounds had significant anti-AChE activity at micromolar or sub-micromolar levels. Among the tested compounds, 3-pyridinium derivative 6m bearing N-(2-bromobenzyl) moiety and 7-methoxy substituent on the benzofuran ring exhibited superior activity. This compound with IC50 value of 0.027 MUM was as potent as standard drug donepezil. PMID- 26363873 TI - How do changes in the population tested for chlamydia over time affect observed trends in chlamydia positivity? Analysis of routinely collected data from young women tested for chlamydia in family planning clinics in the Pacific Northwest (USA), between 2003 and 2010. AB - Background The proportion of chlamydia tests that are positive (positivity) is dependent on the population tested and the test technology used. The way in which changes in these variables might affect trends in positivity over time is investigated. METHODS: Data from 15- to 24-year-old women tested for chlamydia in family planning clinics participating in the Infertility Prevention Project in the Pacific Northwest, United States (USA Public Health Service Region X) during 2003-2010 (n=590557) were analysed. Trends in positivity and in test, demographic and sexual behaviour variables were identified. Unadjusted and adjusted trends in chlamydia positivity were calculated using logistic regression. RESULTS: The proportion of tests carried out using nucleic acid amplification tests (NAATs) increased dramatically during the analysis period in two states. Smaller changes in demographic and behavioural characteristics were seen. Controlling for test technology used had the largest effect on the trend in testing positive per year, leading to a fall in the calculated odds ratio of testing positive from 1.06 to 1.02 in Oregon, and from 1.07 to 1.02 in Idaho. Controlling for other variables had minimal effect on chlamydia positivity trends. CONCLUSIONS: Changes in NAAT use had a large effect on observed trends in chlamydia positivity over time in the two states where NAATs were introduced during the analysis period. While trends in chlamydia positivity may be a useful metric for monitoring chlamydia burden, it is important to consider changes in test type when interpreting these data. PMID- 26363874 TI - Chemical constituents of plants from the genus Buxus. PMID- 26363875 TI - Mitsunobu alkylation of cancerostatic 5-fluorouridine with (2E)-10-hydroxydec-2 enoic acid, a fatty acid from royal jelly with multiple biological activities. AB - 5-Fluorouridine (1) - a nucleoside antimetabolite with strong cancerostatic properties - was protected i) at the 2'- and 3'-OH groups with a heptan-4-ylidene residue and ii) at the 5'-OH group with a (4-methoxyphenyl)(diphenyl)methyl residue. This fully protected compound, 3, was submitted to a Mitsunobu reaction with the N-hydroxysuccinimide (NHS) ester, 5, of (2E)-10-hydroxydec-2-enoic acid (4) which gave nucleolipid 6. The latter was detritylated with Cl2 CHCOOH to yield the co-drug 7 as NHS ester. PMID- 26363876 TI - Secondary metabolites from Aspergillus fumigatus, an endophytic fungus from the liverwort Heteroscyphus tener (Steph.) Schiffn. AB - Three new metabolites, asperfumigatin (1), isochaetominine (10), and 8'-O methylasterric acid (21), together with nineteen known compounds, were obtained from the culture of Aspergillus fumigatus, an endophytic fungus from the Chinese liverwort Heteroscyphus tener (Steph.) Schiffn. Their structures were established by extensive analysis of the spectroscopic data. The absolute configurations of 1 and 10 were determined by analysis of their respective CD spectra. Cytotoxicity of these isolates against four human cancer cell lines was also determined. PMID- 26363877 TI - Argania spinosa var. mutica and var. apiculata: variation of fatty-acid composition, phenolic content, and antioxidant and alpha-amylase-inhibitory activities among varieties, organs, and development stages. AB - Argania spinosa includes two varieties, var. apiculata and var. mutica. These argan varieties were introduced into Tunisia in ancient times and are actually cultivated in some botanic gardens. Little is known about the chemical differentiation among these argan varieties. Hence, the aim of this study was to determine the fatty-acid composition, the total phenolic and flavonoid contents, and the antioxidant and alpha-amylase-inhibitory activities of leaf, seed, and pulp extracts of both argan varieties harvested during the months of January to April. The fatty-acid distribution was found to depend on the argan variety, the plant organ, and the harvest time. Significant variations in the phenolic contents were observed between the investigated varieties as well as between leaves, pulps, and seeds of each variety. As expected, phenolic compounds were found to be contributors to the antioxidant and alpha-amylase-inhibitory activities of both argan varieties. The chemical differentiation observed among the two argan varieties, based mainly on the fatty-acid composition, might have some chemotaxonomic value. PMID- 26363878 TI - Recent findings in the chemistry of odorants from four Baccharis species and their impact as chemical markers. AB - Baccharis is a widespread genus belonging to the Asteraceae family that includes almost 400 species exclusively from the Americas. Even when studied in detail, the taxonomic classification among species from this genus is not yet fully defined. Within the framework of our study of the volatile composition of the Baccharis genus, four species (B. trimera, B. milleflora, B. tridentata, and B. uncinella) were collected from the 'Campos de Cima da Serra' highlands of the Brazilian state of Rio Grande do Sul. The aerial parts were dried and extracted by the simultaneous distillation extraction (SDE) procedure. This is the first time that SDE has been applied to obtain and compare the volatile-extract composition in the Baccharis genus. Characterization of the volatile extracts allowed the identification of 180 peaks with many coeluting components; these latter being detailed for the first time for this genus. The multivariate statistical analyses allowed separating the volatile extracts of the four populations of Baccharis into two separate groups. The first one included the B. milleflora, B. trimera, and B. uncinella volatile extracts. The three species showed a high degree of similarity in their volatile composition, which was characterized by the presence of high contents of sesquiterpene compounds, in particular of spathulenol. The second group comprised the extract of B. tridentata, which contained alpha-pinene, beta-pinene, limonene, and (E)-beta ocimene in high amounts. PMID- 26363879 TI - Polyketides from mantis-associated fungus Daldinia eschscholzii IFB-TL01. AB - Three new polyketides, named daldinone F (1), nodulisporin G (2), and dalmanol C (3), together with five known compounds, 4-8, were isolated from cultures of Daldinia eschscholzii. The structures of the new compounds were elucidated by extensive NMR and MS analyses. Compound 1 showed moderate cytotoxic activity against SW480 cancer cells with an IC50 value of 9.59 MUM, and its absolute configuration was determined by single crystal X-ray diffraction. PMID- 26363881 TI - Studying the structural and folding features of long-sequence trichobrachin peptides. AB - In this theoretical study, the folding processes of long-sequence trichobrachin peptides (i.e., TB IIb peptides) were investigated by molecular dynamics methods. The formation of various helical structures (i.e., 310 -, alpha-, and left-handed alpha-helices) was studied with regard to the entire sequence of peptides, as well as to each amino acid. The results pointed out that TB IIb molecules showed a propensity to form helical conformations, and they could be characterized by 310 -helical structure rather than by alpha-helical structure. The formation of local (i.e., i<-i+3 and i<-i+4) as well as of non-local (i.e., i<-i+n, where n>4; and all i->i+n) H-bonds was also examined. The results revealed that the occurrence of local, helix-stabilizing H-bonds was in agreement with the appearance of helical conformations, and the non-local H-bonds did not produce relevant effects on the evolution of helical structures. Based on the data obtained by our structural investigation, differences were observed between the TB IIb peptides, according to the type of amino acid located in the 17th position of their sequences. In summary, the folding processes were explored for TB IIb molecules, and our theoretical study led to the conclusion that these long sequence peptaibols showed characteristic structural and folding features. PMID- 26363880 TI - Diterpenes from the roots of Oryza sativa L. and their inhibition activity on NO production in LPS-stimulated RAW264.7 macrophages. AB - Two new pimarane diterpenoids, momilactone D (3) and momilactone E (5), along with three known diterpenoids, momilactone A (1), sandaracopimaradien-3-one (2), and oryzalexin A (4) were isolated from Oryza sativa roots. The chemical structures of the compounds were determined by spectroscopic data analysis. The isolated diterpenoids were evaluated for their ability to inhibit NO production and iNOS mRNA and protein expression in LPS-stimulated RAW264.7 macrophages. Compound 4 showed strong inhibition activity on NO production, and compounds 1 and 4 decreased the expression of iNOS mRNA and protein levels. PMID- 26363882 TI - Essential oils and diethyl ether extracts of Serbian Xeranthemum cylindraceum and X. annum: chemical composition, antimicrobial activity, and chemotaxonomic implications. AB - Detailed GC and GC-MS analyses of the essential oils and Et2 O extracts of two Xeranthemum species - X. cylindraceum and X. annum - resulted in the identification of 254 components, in total. Terpenoids constituted the major part of both X. cylindraceum and X. annum essential oils and extracts (51.8-65.7%, and 50.7%, resp.). Among the sesquiterpenoids, the extracts of both investigated taxa contained the guaianolide xerantholide, its 11,13-dihydro derivatives, and two additional sesquiterpene lactones: an eudesmanolide, 11,13 dihydroisoalantolactone, and a pseudoguaianolide, confertin. The last two lactones and both isomers of 11,13-dihydroxerantholide have not been previously detected in Xeranthemum species. The isolated extracts of X. cylindraceum and X. annum were tested in a broth microdilution assay against a panel of microorganisms. The tested extracts demonstrated significant antimicrobial inhibitory activity, ranging from 30 to 260 MUg/ml, being most active against Bacillus cereus and Staphylococcus aureus, an important human pathogen, with MIC close in value to those of chloramphenicol. Chemotaxonomic significance of the sesquiterpene lactones' distribution in the taxa investigated in this study and those detected earlier in phylogenetically close species (up to the level of the tribe Cardueae) was also discussed. PMID- 26363884 TI - Merosesquiterpenoids and ten-membered macrolides from a soft coral-derived Lophiostoma sp. fungus. AB - One new merosesquiterpenoid, craterellin D (1), along with one known analog, craterellin A (2), and five known ten-membered macrolides, 3-7, were isolated from a soft coral-derived Lophiostoma sp. fungus. The absolute configuration of 1 was established based on biogenetic consideration with the co-isolated analog 2, whose configuration was determined by modified Mosher's method and single-crystal X-ray diffraction analysis using CuKalpha radiation. The absolute configuration of 3 was determined by X-ray diffraction analysis using CuKalpha radiation. Compounds 2 and 3 showed antibacterial activities against Bacillus cereus with a MIC value of 3.12 MUM. PMID- 26363883 TI - Bioactive steroid derivatives and butyrolactone derivatives from a gorgonian derived Aspergillus sp. fungus. AB - Six steroid derivatives, 1-6, and five butyrolactone derivatives, 7-11, were isolated from the fermentation broth of a gorgonian-derived Aspergillus sp. fungus. Their structures were elucidated on the basis of NMR and MS spectral data. Compound 1 is a new, highly conjugated steroid. The NMR and MS data of 7 and 8 are reported for the first time, as their structures were listed in SciFinder Scholar with no associated reference. Compounds 1, 4, 5, and 8-11 inhibited the larval settlement of barnacle Balanus amphitrite with EC50 values ranging from 0.63 to 18.4 MUg ml(-1) . Butyrolactone derivatives 7 and 8 showed pronounced antibacterial activities against Staphylococcus aureus with the same MIC values as the positive control ciprofloxacin (MIC 1.56 MUM for all three compounds). PMID- 26363885 TI - Effect of volatile organic compounds from bacteria on nematodes. AB - The five studied bacterial strains could produce volatile organic compounds (VOCs) that kill nematodes. Based on their 16S rRNA sequences, these strains were identified as Pseudochrobactrum saccharolyticum, Wautersiella falsenii, Proteus hauseri, Arthrobacter nicotianae, and Achromobacter xylosoxidans. The bacterial VOCs were extracted using solid-phase micro-extraction (SPME) and subsequently identified by GC/MS analysis. The VOCs covered a wide range of aldehydes, ketones, alkyls, alcohols, alkenes, esters, alkynes, acids, ethers, as well as heterocyclic and phenolic compounds. Among the 53 VOCs identified, 19 candidates, produced by different bacteria, were selected to test their nematicidal activity (NA) against Caenorhabditis elegans and Meloidogyne incognita. The seven compounds with the highest NAs were acetophenone, S-methyl thiobutyrate, dimethyl disulfide, ethyl 3,3-dimethylacrylate, nonan-2-one, 1-methoxy-4-methylbenzene, and butyl isovalerate. Among them, S-methyl thiobutyrate showed a stronger NA than the commercial insecticide dimethyl disulfide. It was reported for the first time here that the five bacterial strains as well as S-methyl thiobutyrate, ethyl 3,3-dimethylacrylate, 1-methoxy-4-methylbenzene, and butyl isovalerate possess NA. These strains and compounds might provide new insights in the search for novel nematicides. PMID- 26363886 TI - Detection of a new piperideine alkaloid in the pygidial glands of some Stenus beetles. AB - Rove beetles of the genus Stenus produce and store bioactive alkaloids like stenusine (3), 3-(2-methylbut-1-enyl)pyridine (4), and cicindeloine (5) in their pygidial glands to protect themselves from predation and microorganismic infestation. The biosynthesis of stenusine (3), 3-(2-methylbut-1-enyl)pyridine (4), and cicindeloine (5) was previously investigated in Stenus bimaculatus, Stenus similis, and Stenus solutus, respectively. The piperideine alkaloid cicindeloine (5) occurs also as a major compound in the pygidial gland secretion of Stenus cicindeloides. The three metabolites follow the same biosynthetic pathway, where the N-heterocyclic ring is derived from L-lysine and the side chain from L-isoleucine. The different alkaloids are finally obtained by few modifications of shared precursor molecules, such as 2,3,4,5-tetrahydro-5-(2 methylbutylidene)pyridine (1). This piperideine alkaloid was synthesized and detected by GC/MS and GC at a chiral phase in the pygidial glands of Stenus similis, Stenus tarsalis, and Stenus cicindeloides. PMID- 26363887 TI - Nematicidal triterpenoids from Lantana camara. AB - A new triterpene, lancamarolide (1), and seven known triterpenes, oleanonic acid (2), lantadene A (3), 11alpha-hydroxy-3-oxours-12-en-28-oic acid (4), betulinic acid (5), lantadene B (6), and lantaninilic acid (7) were isolated from the aerial parts of Lantana camara in the course of bioassay-guided isolation, and their nematicidal activities against Meloidogyne incognita, the root knot nematode, were carried out. Oleanonic acid was found to be the most active compound and exhibited 80% mortality after 72 h at 0.0625% concentration, which is comparable with that of the standard furadan. PMID- 26363888 TI - Comments on: Prone and direct posterior approach for management of posterior column tibial plateau fractures of K.-C. Lin, Y.-W. Tarng, G.-Y. Lin, S.-W. Yang, C.-J. Hsu, J.-H. Renn published in Orthop Traumatol Surg Res 2015;101(4):477-482. PMID- 26363889 TI - Actifit(r) scaffold implantation: Influence of preoperative meniscal extrusion on morphological and clinical outcomes. AB - BACKGROUND: Meniscal substitutes have been suggested for the treatment of knee pain after partial meniscectomy. However, despite the partial nature of the initial meniscectomy, secondary extrusion of the substitute is common. The primary objective of this study was to evaluate morphological outcomes of meniscal substitute implantation and their potential associations with preoperative meniscal extrusion. HYPOTHESIS: Preoperative absolute meniscal extrusion in the coronal plane predicts poorer morphological and clinical outcomes. MATERIAL AND METHODS: Consecutive patients who received an Actifit((r)) meniscal substitute between 2008 and 2011 were included prospectively. After 1 year and 2 years, the IKDC score and KOOS were determined and magnetic resonance imaging performed. The morphological evaluation consisted in measuring meniscal extrusion and cartilage coverage by the substitute in the coronal and sagittal planes. RESULTS: Twenty patients were included. Among them, 3 required subsequent removal of the substitute. The mean subjective IKDC score increased from 48.1 preoperatively to 56.4 after 2 years. Over the same period, the function/sports/recreational activities component of the KOOS improved significantly (42.9 vs. 55.0, P=0.04). Positive correlations between preoperative and 1-year values were demonstrated for both cartilage coverage in the coronal and the sagittal planes (P=0.03 and P=0.04, respectively) and coronal absolute meniscal extrusion (P=0.05). No significant differences were found between preoperative and 2-year values of cartilage coverage in the coronal and sagittal planes (P=0.38). There was a negative correlation linking preoperative meniscal extrusion in the coronal plane to 1-year cartilage coverage in the coronal and sagittal planes (P=0.01 and P=0.04, respectively). Preoperative absolute meniscal extrusion in the coronal plane correlated negatively with the subjective IKDC score after 1 year (P=0.02). DISCUSSION: Preoperative meniscal extrusion in the coronal plane strongly predicts clinical and morphological outcomes. Marked preoperative meniscal extrusion, even in a patient with symptoms after partial meniscectomy, should prompt an appraisal of whether allograft replacement may be more appropriate than a meniscal substitute. LEVEL OF EVIDENCE: IV, prospective study. PMID- 26363890 TI - Comments on: Double tendon transfer for the correction of drop-foot by M.-Y. Grauwin, G. Wavreille, C. Fontaine published in Orthop Traumatol Surg Res 2015;101(1):115-8. PMID- 26363891 TI - The network of molecular chaperones: insights in the cellular proteostasis machinery. PMID- 26363892 TI - Comparing treatment policies with assistance from the structural nested mean model. AB - Treatment policies, also known as dynamic treatment regimes, are sequences of decision rules that link the observed patient history with treatment recommendations. Multiple, plausible, treatment policies are frequently constructed by researchers using expert opinion, theories, and reviews of the literature. Often these different policies represent competing approaches to managing an illness. Here, we develop an "assisted estimator" that can be used to compare the mean outcome of competing treatment policies. The term "assisted" refers to the fact estimators from the Structural Nested Mean Model, a parametric model for the causal effect of treatment at each time point, are used in the process of estimating the mean outcome. This work is motivated by our work on comparing the mean outcome of two competing treatment policies using data from the ExTENd study in alcohol dependence. PMID- 26363893 TI - Thoraco dorsal artery perforator flap for trismus release in a young girl. AB - Trismus is a frequent complication occurring after treatment of tumors of the pterygomaxillary fossa. Local flaps and full-thickness skin grafts fail to release it because they usually lead to scar contracture in previously irradiated tissues. We propose to release it with a thoracodorsal artery perforator flap, which is feasible in children like other perforator flaps. It is interesting because it is thinner than the anterolateral thigh flap and its scar may be less disgraceful and easier to hide. PMID- 26363894 TI - Understanding paediatric allergic fungal sinusitis: Is it more aggressive? AB - OBJECTIVE: To study and characterize the features of AFRS in children as compared to adults. METHODS: 50 consecutive patients of AFRS attending our outpatient department were included in the study from July 2011 to December 2013. They were divided into two groups (A and B) according to age being <=14 years and >14 years. Clinical history and examination included anterior rhinoscopy, SNOT 20 scores, CT of Nose and PNS (para nasal sinuses) (Lund Mackay scores), diagnostic nasal endoscopy (Kupferberg's grades), punch biopsy from nasal polyp, serum IgE, absolute eosinophil counts (AEC) and Aspergillus skin hypersensitivity test was done in all patients for conformation of AFRS. Bent and Kuhn's criteria were used for diagnosis. Sweat chloride levels were done in all patients of group A. RESULTS: Group A had 12 patients and group B had 38. Mean duration of symptoms was significantly less in children as compared to adults (p<0.05). All patients of both groups had nasal polyposis at presentation. Unilateral disease and multisinus involvement was more common in children (6/12) as compared to adults. Proptosis (2/12) and telecanthus (4/12) was more common in children (group A) as compared to adults (group B). LM (Lund Mackay) scores and serum IgE were significantly high in children as compared to adults. Follow up CT scans showed early evidence of recurrence in children as compared to adults (p<0.05). CONCLUSION: AFRS was seen to be more aggressive in children with increased fungal load when compared with adults. Typically, AFRS in children was less responsive to treatment with increased recurrence rates. PMID- 26363895 TI - Skeletal facial deformity in patients with beta thalassemia major: Report of one Tunisian case and a review of the literature. AB - beta Thalassemia is an inherited genetic disorder of hemoglobin synthesis characterized by a reduction of beta chains of globin. Typical features of patients with beta thalassemia are skeletal modifications, particularly in the skull and in the facial bones. In thalassemia major, involvement of the facial skeleton can result in severe disfigurement, often referred to as "rodent facies". Various surgical approaches to correct the facial deformity have been advocated; however, treatment remains controversial. The worse the patient's systemic condition, the more unstable and more complicated the surgical procedure. Patient with multisystemic disorder and severe deformity, such as in our case, with a complete lack of cortical bone for bone fixation, might not be amenable to such procedures. Thorough knowledge of the multiple systemic manifestations, therapy, and prognosis of this syndrome is necessary to formulate a safe, comprehensive surgical plan for these patients. PMID- 26363896 TI - Cyclin D1 and Ewing's sarcoma/PNET: A microarray analysis. AB - Recent immunohistochemical analyses have showed that cyclin D1 is expressed in soft tissue Ewing's sarcoma/peripheral neuroectodermal tumor (PNET) of childhood and adolescents, while it is undetectable in both embryonal and alveolar rhabdomyosarcoma. In the present paper, microarray analysis provided evidence of a significant upregulation of cyclin D1 in Ewing's sarcoma as compared to normal tissues. In addition, we confirmed our previous findings of a significant over expression of cyclin D1 in Ewing sarcoma as compared to rhabdomyosarcoma. Bioinformatic analysis also allowed to identify some other genes, strongly correlated to cyclin D1, which, although not previously studied in pediatric tumors, could represent novel markers for the diagnosis and prognosis of Ewing's sarcoma/PNET. The data herein provided support not only the use of cyclin D1 as a diagnostic marker of Ewing sarcoma/PNET but also the possibility of using drugs targeting cyclin D1 as potential therapeutic strategies. PMID- 26363897 TI - The future of the EANS Neurosurgeons of Europe, unite! PMID- 26363898 TI - Clinical, biological, and microbiological pattern associated with ventriculostomy related infection: a retrospective longitudinal study. AB - BACKGROUND: Our aim was to describe the pattern of ventriculostomy-related infection (VRI) development using a dynamic approach. STUDY DESIGN: Retrospective longitudinal study. METHODS: We analyzed the files of 449 neurosurgical patients who underwent placement of external ventricular drain (EVD). During the study period, CSF sampling was performed on a daily base setting. VRI was defined as a positive CSF culture resulting in antibiotic treatment. For VRI patients, we arbitrary defined day 0 (D0) as the day antibiotic treatment was started. In these patients, we compared dynamic changes in clinical and biological parameters at four pre-determined time points: (D-4, D-3, D-2, D-1) with those of D0. For all CSF-positive cultures, we compared CSF biochemical markers' evolution pattern between VRI patients and the others, considered as a control cohort. RESULTS: Thirty-two suffered from VRI. Peripheral white blood cell count did not differ between D-4-D0. Median body temperature, CSF cell count, median Glasgow Coma Scale, CSF protein, and glucose concentrations were significantly different between D-4, D-3, D-2, and D0. At D0, 100 % of CSF samples yielded organisms in culture. The physician caring for the patient decided to treat VRI based upon positive CSF culture in only 28 % (9/32) of cases. In the control cohort, CSF markers' profile trends to normalize, while it worsens in the VRI patients. CONCLUSIONS: We showed that clinical symptoms and biological abnormalities of VRI evolved over time. Our data suggest that VRI decision to treat relies upon a bundle of evidence, including dynamic changes in CSF laboratory exams combined with microbiological analysis. PMID- 26363899 TI - Lack of ethnic differences in the pharmacokinetics and pharmacodynamics of inclacumab in healthy Japanese and Caucasian subjects. AB - PURPOSE: Inclacumab, a novel monoclonal antibody against P-selectin, is in development for the treatment and prevention of atherosclerotic cardiovascular diseases. This study was conducted to investigate potential differences in the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single intravenous doses of inclacumab between Japanese and Caucasian healthy volunteers. METHOD: Sixty-two subjects (31 Japanese and 31 Caucasian) were enrolled in a single-center, open-label, parallel, three dose groups (0.3, 3.0, and 20 mg/kg), single-dose study in Japanese and Caucasian healthy volunteers. Inclacumab concentrations, platelet-leukocyte aggregates (PLA), free/total soluble P-selectin (sP-selectin) ratio, and antibody formation were measured along with routine safety monitoring during the conduct of the study. RESULTS: The PK profiles of inclacumab in Caucasian and Japanese subjects were similar following single-dose intravenous infusion. The statistical analysis of peak (C max) and total exposure (AUClast) indicated that bioavailability was similar for both races when corrected for body weight. The geometric mean ratios for AUClast and C max in the Japanese versus Caucasian cohort were 101 and 111%, respectively, in 0.3 mg/kg dose group, 108 and 107%, respectively, in 3.0 mg/kg dose group, and 97 and 96%, respectively, in 20 mg/kg dose group. No differences were observed in the level of PLA inhibition and mean free/total soluble P selectin ratio between Japanese and Caucasian subjects. PK/PD relationship between the free/total sP-selectin ratio or PLA and plasma concentration of inclacumab appeared to be similar in both Japanese and Caucasian populations. The effect of race as a covariate was explored on both PK/PD models for PLA and free/total sP-selectin ratio and did not have a significant effect over the reduced model without race as a covariate. CONCLUSIONS: Ethnicity had no clinically relevant influence on inclacumab pharmacokinetics or pharmacodynamics. No dose adjustment of inclacumab is required for differences in race. PMID- 26363901 TI - Clinically suspected heparin-induced thrombocytopenia during extracorporeal membrane oxygenation. AB - PURPOSE: Patients receiving extracorporeal membrane oxygenation (ECMO) are at risk for thrombocytopenia including heparin-induced thrombocytopenia (HIT). The purpose of this study was to determine the frequency of suspected HIT in patients receiving ECMO and unfractionated heparin (UFH). MATERIALS AND METHODS: We conducted a retrospective review in adult patients on ECMO. Patients were included if they received ECMO for at least 5 days and concomitant UFH. RESULTS: There were 119 patients who met inclusion criteria. Twenty-three patients (19%) had a heparin-platelet factor 4 immunoassay performed. Patients with suspected HIT had a significantly lower platelet count within the first 3 days of ECMO, 69*10(9)/L (22-126*10(9)/L) vs 87.5*10(9)/L (63-149*10(9)/L); P=.04. The lowest platelet count on the day of HIT testing was 43*10(9)/L (26-73), representing a 71% reduction from baseline. Twenty patients (87%) had an optical density score less than 0.4, and all patients had a score less than 1.0. A functional assay was performed in 7 patients (30%), with only 1 patient having laboratory-confirmed HIT. CONCLUSIONS: The evaluation of HIT occurred in a small percentage of patients, with HIT rarely being detected. Patients who had heparin-platelet factor 4 immunoassay testing exhibited lower platelet counts with a similar duration of ECMO and UFH exposure. PMID- 26363900 TI - Anxious-depression among Hispanic/Latinos from different backgrounds: results from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). AB - BACKGROUND: Anxious-depression is a constellation of symptoms, frequently encountered among patients in primary care centers. There is a need to study how anxious-depression presents among Hispanic/Latinos of different backgrounds. OBJECTIVE: To study the construct of anxious-depression among 16,064 Hispanic/Latinos of different backgrounds participating in the Hispanic Community Health Study/Study of Latinos. We hypothesized that Hispanic/Latinos will cluster in 3 classes: low anxiety/high depression, high anxiety/low depression and a combined anxious-depression construct. METHODS: Using latent profile analysis, symptoms of depression and anxiety measured by the 10-item Center for Epidemiologic Studies Depression Scale and 10-item State-Trait Anxiety Inventory were evaluated to determine if an anxious-depression typology would result. A multinomial logistic regression analysis explored the association of the 3-class solution with different Hispanic/Latino backgrounds controlling for age, gender, language, education and income. RESULTS: A 3-class mixed anxious-depression structure emerged with 10% of Hispanic/Latinos in the high, 30% in the moderate and 60% in the low anxious-depression category. After adjusting for age, gender, language preference, income and education, individuals of Puerto Rican background were more likely to experience high (OR = 1.79, p < 0.05) and moderate (OR = 1.36, p < 0.05) (vs. low) anxious-depression symptomatology compared to those of Mexican background. Individuals of Central American and South American background were less likely to experience high (OR = 0.68, p < 0.05) and moderate (OR = 0.8, p < 0.05) (vs. low) anxious-depression compared to those of Mexican background. CONCLUSION: Anxious-depression symptomatology varied among this sample of Hispanic/Latino groups. These classes should be investigated as to their relationship with different health outcomes relevant to the Hispanic/Latino of different backgrounds. PMID- 26363902 TI - Gastric Stenosis After Laparoscopic Sleeve Gastrectomy: Diagnosis and Management. AB - PURPOSE: The use of laparoscopic sleeve gastrectomy (LSG) is increasing worldwide. Although post-LSG gastric stenosis (GS) is less frequent, it has not been well defined and lacks standardized management procedures. The objective of the present study was to describe a series of patients with GS symptoms after LSG and to develop a standardized management procedure for this complication. METHODS: We performed a retrospective analysis of a prospective database of patients presenting with GS after LSG procedures performed between January 2008 and March 2014. The primary efficacy criterion was the frequency of post-LSG GS. GS was classified as functional (i.e. a gastric twist) or organic. The secondary efficacy criteria included the time interval between LSG and diagnosis of GS, the type of stenosis, the type of management, and the follow-up data. RESULTS: During the study period, 1210 patients underwent primary or secondary LSG. Seventeen patients had post-operative symptoms of GS (1.4%); one patient had achalasia that had not been diagnosed preoperatively and thus was excluded from our analysis. The median time interval between LSG and diagnosis of GS was 47.2 days (1-114). Eleven patients had organic GS and six had functional GS. Seven patients required nutritional support. Endoscopic treatment was successful in 15 patients (88.2%) after balloon dilatation (n = 13) or insertion of a covered stent (n = 2). Two of the 15 patients required conversion to Roux-en-Y gastric bypass (11.8%). CONCLUSION: GS after LSG is a rare complication but requires standardized management. Most cases can be treated successfully with endoscopic balloon dilatation. PMID- 26363903 TI - Simultaneous evaluation of brain tumour metabolism, structure and blood volume using [(18)F]-fluoroethyltyrosine (FET) PET/MRI: feasibility, agreement and initial experience. AB - PURPOSE: Both [(18)F]-fluoroethyltyrosine (FET) PET and blood volume (BV) MRI supplement routine T1-weighted contrast-enhanced MRI in gliomas, but whether the two modalities provide identical or complementary information is unresolved. The aims of the study were to investigate the feasibility of simultaneous structural MRI, BV MRI and FET PET of gliomas using an integrated PET/MRI scanner and to assess the spatial and quantitative agreement in tumour imaging between BV MRI and FET PET. METHODS: A total of 32 glioma patients underwent a 20-min static simultaneous PET/MRI acquisition on a Siemens mMR system 20 min after injection of 200 MBq FET. The MRI protocol included standard structural MRI and dynamic susceptibility contrast (DSC) imaging for BV measurements. Maximal relative tumour FET uptake (TBRmax) and BV (rBVmax), and Dice coefficients were calculated to assess the quantitative and spatial congruence in the tumour volumes determined by FET PET, BV MRI and contrast-enhanced MRI. RESULTS: FET volume and TBRmax were higher in BV-positive than in BV-negative scans, and both VOLBV and rBVmax were higher in FET-positive than in FET-negative scans. TBRmax and rBVmax were positively correlated (R (2) = 0.59, p < 0.001). FET and BV positivity were in agreement in only 26 of the 32 patients and in 42 of 63 lesions, and spatial congruence in the tumour volumes as assessed by the Dice coefficients was generally poor with median Dice coefficients exceeding 0.1 in less than half the patients positive on at least one modality for any pair of modalities. In 56 % of the patients susceptibility artefacts in DSC BV maps overlapped the tumour on MRI. CONCLUSION: The study demonstrated that although tumour volumes determined by BV MRI and FET PET were quantitatively correlated, their spatial congruence in a mixed population of treated glioma patients was generally poor, and the modalities did not provide the same information in this population of patients. Combined imaging of brain tumour metabolism and perfusion using hybrid PET/MR systems may provide complementary information on tumour biology, but the potential clinical value remains to be determined in future trials. PMID- 26363904 TI - Anomalous d-like surface resonances on Mo(110) analyzed by time-of-flight momentum microscopy. AB - The electronic surface states on Mo(110) have been investigated using time-of flight momentum microscopy with synchrotron radiation (hnu=35 eV). This novel angle-resolved photoemission approach yields a simultaneous acquisition of the E vs-k spectral function in the full surface Brillouin zone and several eV energy interval. (kx,ky,EB)-maps with 3.4 A(-1) diameter reveal a rich structure of d like surface resonances in the spin-orbit induced partial band gap. Calculations using the one-step model in its density matrix formulation predict an anomalous state with Dirac-like signature and Rashba spin texture crossing the bandgap at Gamma- and EB=1.2 eV. The experiment shows that the linear dispersion persists away from the Gamma--point in an extended energy- and k?-range. Analogously to a similar state previously found on W(110) the dispersion is linear along H--Gamma- H- and almost zero along N--Gamma--N-. The similarity is surprising since the spin-orbit interaction is 5 times smaller in Mo. A second point with unusual topology is found midway between Gamma- and N-. Band symmetries are probed by linear dichroism. PMID- 26363905 TI - Escaping herbivory: ocean warming as a refuge for primary producers where consumer metabolism and consumption cannot pursue. AB - Ocean warming is anticipated to strengthen the persistence of turf-forming habitat, yet the concomitant elevation of grazer metabolic rates may accelerate per capita rates of consumption to counter turf predominance. Whilst this possibility of strong top-down control is supported by the metabolic theory of ecology (MTE), it assumes that consumer metabolism and consumption keep pace with increasing production. This assumption was tested by quantifying the metabolic rates of turfs and herbivorous gastropods under a series of elevated temperatures in which the ensuing production and consumption were observed. We discovered that as temperature increases towards near-future levels (year 2100), consumption rates of gastropods peak earlier than the rate of growth of producers. Hence, turfs have greater capacity to persist under near-future temperatures than the capacity for herbivores to counter their growth. These results suggest that whilst MTE predicts stronger top-down control, understanding whether consumer producer responses are synchronous is key to assessing the future strength of top down control. PMID- 26363906 TI - Dissecting the smell of fear from conspecific and heterospecific prey: investigating the processes that induce anti-predator defenses. AB - Prey use chemical cues from predation events to obtain information about predation risk to alter their phenotypes. Though we know how many prey respond to predators, we still have a poor understanding of the processes and chemical cues involved during a predation event. We examined how gray treefrog tadpoles (Hyla versicolor) altered their behavior and morphology when raised with cues from different stages of predator attack, predators fed different amounts of prey, and predators consuming different combinations of treefrog tadpoles or snails (Helisoma trivolvis). We found that starved predators and predators fed snails induced no defensive responses whereas tadpoles exposed to a predator consuming gray treefrogs induced greater hiding, lower activity, and relatively deeper tails. We also found that the tadpoles did not respond to crushed, chewed, or digested conspecifics, but they did respond to consumed (i.e., chewed plus digested) conspecifics. When we increased the treefrog biomass consumed by predators, tadpoles frequently increased their defenses when only tadpoles were consumed and always increased their defenses when the total diet biomass was held constant via the inclusion of snails. When predators experienced temporal variation in diet composition, including cues from snails to cause additional digestive cues or chemical noise, there was no effect on tadpole phenotypes. Our results suggest that amphibian prey rely on cues from both chewing and digestion of conspecifics and that the presence of cues from digested heterospecifics play little or no role in adding chemical noise or increased digestive enzymes and by products that could potentially interfere with induced defenses. PMID- 26363907 TI - Treatment of Myasthenia Gravis in the Aged. AB - Myasthenia gravis is diagnosed at a progressively later age and the incidence continuously increases in the aged with a clear male predominance. People above the age of 65 constitute more than 50% of the newly diagnosed. Commonly, patients present with focal (ocular or bulbar) weakness. A high index of suspicion is needed to achieve early diagnosis and improve prognosis. Management options include acetylcholinesterase inhibitors, steroids, and immunosuppressants. Of the immunosuppressants, azathioprine is one of the most widely used due to its demonstrated effect and favorable side-effect profile. Others include cyclosporine, tacrolimus, mycophenolate mofetil, and cyclophosphamide. The use of mycophenolate mofetil is still controversial. Monoclonal antibodies, like rituximab, eculizumab, and belimumab, are relatively new therapeutic options in autoimmune diseases. Rituximab is of special interest in muscle-specific tyrosine kinase antibody-positive patients. A novel skeletal muscle activator and stem cell transplantation are being studied. There is no place for standard thymectomy in the older age groups except for thymomas and with computer-assisted endoscopy. Generally, the disease responds well to treatment at this age but comorbidities make medication choice more complex. Successful treatment is associated with improved survival, and quality of life can be remarkably improved during the whole survival period. As the median age of onset is 65 years and has been increasing steadily, it appears necessary to review the subject of treatment of myasthenia gravis in the aged. PMID- 26363908 TI - Neuropathic Pain Among Community-Dwelling Older People: A Clinical Study in Finland. AB - BACKGROUND: Neuropathic pain is more common among older people than in the general population, and the efficacy of medical treatment often remains unsatisfactory. OBJECTIVE: The aim of this study was to assess the presence, diagnostic certainty, etiology and treatment of neuropathic pain in community dwelling older people with chronic pain. METHODS: Independently living older people aged 75, 80 and 85 years subject to communal preventive home visits with chronic pain were invited to a clinical pain examination by a geriatrician. RESULTS: Overall, 106 patients consented to participate in the clinical study. Neuropathic pain was diagnosed in 51 (48%) patients, with 75% of pain states definite and 25% probable neuropathic pain. The most common etiology was degenerative disease of the spinal column causing radiculopathy. At the study visit, 11 patients (22% of neuropathic pain patients) were receiving medication that was demonstrated to be effective against neuropathic pain. The geriatrician recommended a trial of a new medicine for 17 patients, but only six continued the medication going forward. CONCLUSIONS: Neuropathic pain was surprisingly common in our cohort. Finding effective pain medication is challenging due to comorbidities, possible side effects, and vulnerability in older age. Other pain management methods should be considered. PMID- 26363909 TI - Use of Statins and Risk of Dementia in Heart Failure: A Retrospective Cohort Study. AB - OBJECTIVE: Heart failure (HF) is associated with an increased risk of dementia, and studies show that dyslipidemia may be involved in the pathogenesis of dementia. However, it is unclear whether 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are associated with a lower risk of dementia in HF patients. The present study examines the effectiveness of statins to prevent dementia in HF patients. METHODS: This retrospective longitudinal study used a cohort of patients with HF identified from a local US Medicare Advantage Prescription Drug plan to examine the incidence of dementia with up to 3 years of follow-up. A multivariable time-dependent Cox model and inverse probability-of-treatment weighting (IPTW) of the marginal structural model were used to estimate the risk of developing dementia. Adjusted dementia rate ratios were estimated among current and former statin users, as compared with nonusers. RESULTS: The study included a total of 8062 HF patients (mean age 74.47 +/- 9.21 years), of whom 1135 (14.08%) were diagnosed with dementia during a median follow up of 22 months. Using the time-dependent Cox model, the adjusted dementia rate ratios among current and former users were 0.93 (95% confidence interval [CI] 0.71-1.21) and 0.99 (95% CI 0.79-1.25), respectively. Use of IPTW resulted in similar findings of 1.24 (95% conservative CI 0.89-1.72) among current users and 0.94 (95% conservative CI 0.67-1.31) among former users as compared with nonusers. CONCLUSION: This study found no difference in the risk of dementia among current and former users of statins as compared with nonusers in an already at-risk HF population. PMID- 26363910 TI - Flavonoids isolated from Tridax procumbens (TPF) inhibit osteoclasts differentiation and bone resorption. AB - BACKGROUND: The Tridax procumbens flavonoids (TPF), are well known for their medicinal properties among local natives. The TPF are traditionally used for dropsy, anaemia, arthritis, gout, asthma, ulcer, piles, and urinary problems. It also used in treating gastric problems, body pain, and rheumatic pains of joints. The TPF have been reported to increase osteogenic functioning in mesenchymal stem cells. However, their effects on osteoclastogenesis remain unclear. The TPF isolated from T. procumbens and investigated the effects of the TPF inhibit on osteoclast differentiation and bone resorption activities using primary osteoclastic cells. Osteoclast formation was assessed by counting the number of tartrate resistant acid phosphatase (TRAP) positive multinucleated cells and by measuring both TRAP activities. RESULTS: The TPF significantly suppressed the RANKL-induced differentiation of osteoclasts and the formation of pits in primary osteoclastic cells. The TPF also decreased the expression of mRNAs related to osteoclast differentiation, including Trap, Cathepsin K, Mmp-9, and Mmp-13 in primary osteoclastic cells. The treatment of primary osteoclastic cells with the TPF decreased Cathepsin K, Mmp-9, and Mmp-13 proteins expression in primary osteoclastic cells. CONCLUSION: These results indicated that TPF inhibit osteoclastogenesis and pits formation activities. Our results suggest that the TPF could be a potential anti-bone resorptic agent to treat patients with bone loss-associated diseases such as osteoporosis. PMID- 26363911 TI - A century later: rediscovery, culturing and phylogenetic analysis of Diploospora rosea, a rare onygenalean hyphomycete. AB - Nearly 100 years after its first discovery, Diploospora rosea was detected on biologically damaged parchment paper in Rome, Italy and isolated from house dust collected in Micronesia. The isolation of this culture permitted morphological study of colony characters, conidium and conidiophore development, and phylogenetic investigations using sequences of nuc 18S rDNA, internal transcribed spacers, and 28S rDNA. The results indicate that D. rosea is an onygenalean fungus, of uncertain taxonomic position, basal or sister to the Gymnoascaceae. Based on observations of the parchments using SEM-Energy Dispersive Spectroscopy, we speculate that the fungus occurs in archival and domestic environments subject to periodic wetting. Its ability to grow on all low water activity media used in the study, including malt extract agar amended with 60% sucrose, confirms its xerophilic nature. PMID- 26363912 TI - Sphingomonas arantia sp. nov., isolated from Hoh Xil basin, China. AB - A Gram-negative, rod-shaped, non-motile, non-spore forming, aerobic, orange pigmented bacterium, designated strain 6P(T), was isolated from a soil sample collected from the Hoh Xil basin, China. Strain 6P(T) grew optimally at 25 degrees C, pH 7.0-7.5 and NaCl concentration of 0-1 % (w/v). Phylogenetic analysis based on 16S rRNA gene sequences showed that strain 6P(T) belongs to the genus Sphingomonas, with high sequence similarity (97.1 %) to Sphingomonas fennica. The DNA-DNA hybridization homology with S. fennica DSM 13665(T) was 45.3 %. The DNA G+C content of the novel strain is 65.3 mol%. The isolate contained Q 10 as the only respiratory quinone. The major polar lipids are diphosphatidylglycerol (DPG), phosphatidylethanolamine (PE), phosphatidylglycerol (PG), phosphatidylcholine (PC) and sphingoglycolipid (SGL). C18:1 omega7c and C16:1 omega7c are the major fatty acids. On the basis of the polyphasic evidence presented, strain 6P(T) represents a novel species of the genus Sphingomonas, for which the name Sphingomonas arantia sp. nov. is proposed. The type strain is 6P(T) (=CGMCC 1.12702(T) = JCM 19855(T)). PMID- 26363913 TI - An Analysis of State Autism Educational Assessment Practices and Requirements. AB - States differ in the procedures and criteria used to identify ASD. These differences are likely to impact the prevalence and age of identification for children with ASD. The purpose of the current study was to examine the specific state variations in ASD identification and eligibility criteria requirements. We examined variations by state in autism assessment practices and the proportion of children eligible for special education services under the autism category. Overall, our findings suggest that ASD identification practices vary across states, but most states use federal guidelines, at least in part, to set their requirements. Implications and recommendations for policy and practice are discussed. PMID- 26363914 TI - Perceived Social Competence and Loneliness Among Young Children with ASD: Child, Parent and Teacher Reports. AB - Perceived loneliness and social competence were assessed for 127 children with ASD without comorbid ID, 4-7 years old, through child self-report. Using an abbreviated version of the Loneliness and Social Dissatisfaction Questionnaire (LSDQ; Cassidy and Asher in Child Dev 63:250-365, 1992), the majority of children reported friendships, yet a considerable proportion also reported social difficulties. Factor analysis of the abbreviated LSDQ identified three factors, which were significantly associated with parent- and teacher-reported variables. Regression analyses revealed parent-reported social skills deficits and teacher reported conflict in the student-teacher relationship to be associated with child reported loneliness. Implications for practice are discussed. PMID- 26363915 TI - Does evaluation of the ligamentous compartment enhance diagnostic utility of sacroiliac joint MRI in axial spondyloarthritis? AB - INTRODUCTION: Inflammation of the sacroiliac joints (SIJ) is a fundamental clinical feature of axial spondyloarthritis (SpA). The anatomy of the irregularly shaped SIJ is complex with an antero-inferior cartilaginous compartment containing central hyaline and peripheral fibrocartilage, and a dorso-superior ligamentous compartment. Several scoring modules to systematically assess SIJ magnetic resonance imaging (MRI) in SpA have been developed. Nearly all of them are based on the cartilaginous joint compartment alone. However, there are only limited data about the frequency of inflammatory lesions in the ligamentous compartment and their potential diagnostic utility in axial SpA. We therefore aimed to evaluate the ligamentous compartment on sacroiliac joint MRI for lesion distribution and potential incremental value towards diagnosis of SpA over and above the traditional assessment of the cartilaginous compartment alone. METHODS: Two independent cohorts of 69 and 88 consecutive back pain patients <=50 years were referred for suspected SpA (cohort A) or acute anterior uveitis plus back pain (cohort B). Patients were classified according to rheumatologist expert opinion based on clinical, radiographic and laboratory examination as having nonradiographic axial SpA (nr-axSpA; n = 51), ankylosing spondylitis (n = 34), or nonspecific back pain (NSBP; n = 72). Five blinded readers assessed SIJ MRI globally for presence/absence of SpA. Bone marrow edema (BME) and fat metaplasia were recorded in the cartilaginous and ligamentous compartment. The incremental value of evaluating the ligamentous additionally to the cartilaginous compartment alone for diagnosis of SpA was graded qualitatively. We determined the lesion distribution between the two compartments, and the impact of the ligamentous compartment evaluation on diagnostic utility. RESULTS: MRI bone marrow lesions solely in the ligamentous compartment in the absence of lesions in the cartilaginous compartment were reported in just 0-2.0/0-4.0 % (BME/fat metaplasia) of all subjects. Additional assessment of the ligamentous compartment was regarded as essential for diagnosis in 0 and 0.6 %, and as contributory in 28.0 and 7.7 % of nr-axSpA patients in cohorts A and B, respectively. Concomitant BME in both compartments was evident in 11.6-42.0 % of nr-axSpA and 2.1-2.4 % of NSBP patients. CONCLUSION: Assessing the ligamentous compartment on SIJ MRI provided no incremental value for diagnosis of axial SpA. However, concomitant BME in both compartments may help discriminate nr-axSpA from NSBP. PMID- 26363917 TI - Failure properties of vena cava tissue due to deep penetration during filter insertion. AB - In this work, we use an in-vitro mechanical test to explore the resistance of biaxially stretched vena cava tissue against deep perforation and a methodology which integrates experimental and numerical modeling to identify constitutive fracture properties of the vena cava. Six sheep vena cava were harvested just after killing, and cyclic uniaxial tension tests in longitudinal and circumferential directions and biaxial deep penetration tests were performed. After that, we use a nonlinear finite element model to simulate in vitro penetration of the cava tissue in order to fit the fracture properties under penetration of the vena cava by defining a cohesive fracture zone. An iterative process was developed in order to fit the fracture properties of the vena cava using the previously obtained experimental results. The proposed solutions were obtained with fracture energy of 0.22 or 0.33 N/mm. In comparison with the experimental data, the simulation using [Formula: see text], [Formula: see text], and [Formula: see text] parameters ([Formula: see text]) is in good agreement with results from penetration experiments of cava tissue. It is noticeable that the parameter estimation process of the fracture behavior is more accurate than the estimation process of the elastic behavior for the toe region of the curve. PMID- 26363918 TI - Reducing the Risks of Firearm Violence in High Schools: Principals' Perceptions and Practices. AB - This study assessed the perceptions and practices of a national sample of secondary school principals regarding reducing firearm violence in high schools. Data were collected via three-wave postal mailings. A 59-item valid and reliable questionnaire was mailed to a national random sample of 800 secondary school principals. Of the 349 principals (46 %) that responded, 17 % reported a firearm incident at their school in the past 5 years. Principals perceived inadequate parental monitoring (70 %), inadequate mental health services (64 %), peer harassment/bullying (59 %), and easy access to firearms (50 %) as the main causes of firearm violence in schools. The three barriers to implementing firearm violence prevention practices were: lack of expertise as to which practices to implement (33 %), lack of time (30 %), and lack of research as to which practices are most effective (30 %). Less than half of schools trained school personnel regarding firearm violence issues. The findings indicate that firearm incidents at schools may be more common than previously thought. A significant portion of principals are at a loss as to what to implement because of a lack of empirical evidence on what is effective. More research is needed to find the most effective school interventions for reducing firearm violence. PMID- 26363919 TI - Evidence of Fluconazole-Resistant Candida Species in Tortoises and Sea Turtles. AB - The aim of this study was to evaluate the antifungal susceptibility of Candida spp. recovered from tortoises (Chelonoidis spp.) and sea turtles (Chelonia mydas, Caretta caretta, Lepidochelys olivacea, Eretmochelys imbricata). For this purpose, material from the oral cavity and cloaca of 77 animals (60 tortoises and 17 sea turtles) was collected. The collected specimens were seeded on 2% Sabouraud dextrose agar with chloramphenicol, and the identification was carried out by morphological and biochemical methods. Sixty-six isolates were recovered from tortoises, out of which 27 were C. tropicalis, 27 C. famata, 7 C. albicans, 4 C. guilliermondii and 1 C. intermedia, whereas 12 strains were obtained from sea turtles, which were identified as Candida parapsilosis (n = 4), Candida guilliermondii (n = 4), Candida tropicalis (n = 2), Candida albicans (n = 1) and Candida intermedia (n = 1). The minimum inhibitory concentrations for amphotericin B, itraconazole and fluconazole ranged from 0.03125 to 0.5, 0.03125 to >16 and 0.125 to >64, respectively. Overall, 19 azole-resistant strains (14 C. tropicalis and 5 C. albicans) were found. Thus, this study shows that Testudines carry azole-resistant Candida spp. PMID- 26363916 TI - MR-proADM Predicts Exercise Capacity and Survival Superior to Other Biomarkers in PH. AB - PURPOSE: Besides the established biomarker NT-proBNP, the new cardiovascular biomarkers MR-proANP, MR-proADM, Copeptin, and CT-proET-1 are promising to evaluate hemodynamics, exercise parameters, and prognosis in patients with pulmonary hypertension (PH). METHODS: 125 consecutive patients with pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH) were prospectively enrolled at five German PH centers. Blood samples were taken during right heart catheterization. The primary study endpoint was the correlation between biomarkers and hemodynamic and exercise parameters. As secondary endpoint, prediction of 1-year mortality was evaluated. RESULTS: MR proADM showed the strongest correlations with 6MWD and VO2peak, whereas NT-proBNP showed the strongest correlations with PVR, PAPm, and CI. In multivariate analysis, only MR-proADM was independently associated with exercise variables, whereas only NT-proBNP independently predicted hemodynamic parameters. All biomarkers were associated with 1-year survival, with MR-proADM showing the highest C index of 0.78. In multivariate analysis, MR-proADM predicted survival independent of age, 6-MWD, CI, RAP, and NT-proBNP. The cut-off of 1.08 nmol/l provided a sensitivity of 83 % and specificity of 66 %. CONCLUSIONS: Different biomarkers reflect distinctive disease aspects in PH. NT-proBNP best predicts hemodynamic impairment while MR-proADM strongly correlates with exercise capacity. Additionally, MR-proADM represents a promising new marker to evaluate prognosis in patients with PAH and CTEPH. Multi-marker strategies should further be evaluated. PMID- 26363920 TI - Paracoccidioidomycosis Mimicking Sarcoidosis: A Review of 8 Cases. AB - Sarcoidosis is a multisystem disorder that is characterized by noncaseous epithelioid cell granulomas, which may affect almost any organ. Thoracic involvement is common and accounts for most of the morbidity and mortality associated with this disease. The diagnosis is based on exhaustive exclusion of differential diagnoses, particularly granulomatous infections. We report data on eight patients with paracoccidioidomycosis mimicking sarcoidosis. Five patients presented with a chronic pulmonary type infection and three had a disseminated form after immunosuppressive treatment. The mycological diagnosis in noncaseating granulomas is emphasized and reviewed. PMID- 26363921 TI - Early Diagnosis of Cutaneous Mucormycosis Due to Lichtheimia corymbifera After a Traffic Accident. AB - A case report of cutaneous mucormycosis and obstacles to early diagnosis is presented. A 38-year-old male was involved in a car accident that led to amputation of both lower limbs. Subsequently, he developed fungal wound infection of the left lower limb stump. The infection was detected very early, although the diagnosis was difficult because only a small area was affected and histopathological examination was initially negative. The infection was proven by microscopy, culture and histopathology. The isolate was identified by sequencing of the rDNA ITS region gene (internal transcribed spacer region of ribosomal DNA) as Lichtheimia corymbifera. Liposomal amphotericin B and surgery were successful in management of the disease. PMID- 26363923 TI - [One-year results on the safety and efficacy of the InnFocus MicroShuntTM depending on placement and concentration of mitomycin C]. AB - PURPOSE: To compare intraocular pressure (IOP) at one year with the InnFocus MicroShunt((r)) with or without cataract surgery with according to placement and concentration of mitomycin C (MMC) DESIGN: A retrospective two-center, two surgeon study (France and Dominican Republic). PATIENTS AND METHODS: Adults with POAG requiring filtering surgery. One MicroShunt((r)) was placed in one eye of each patient. The effect of concentration and site of application of MMC was assessed by IOP and medication reduction at one year. RESULTS: Eighty-seven eyes were studied with one-year follow-up. Twenty-three eyes treated with 0.4 mg/mL MMC close to the limbus demonstrated a 55% reduction in IOP from 23.8 +/- 5.3 at baseline to 10.7 +/- 2.8 mmHg at one year. Topical glaucoma medication/patient was reduced 85% from 2.4 +/- 0.9 to 0.3 +/- 0.8. Thirty-one eyes treated with 0.2mg/mL MMC close to the limbus demonstrated a 52% reduction in IOP from 27.9 +/ 6.7 at baseline to 13.3 +/- 3.3 mmHg at one year. Topical glaucoma medication/patient was reduced 88% from 2.5 +/- 1.4 to 0.5 +/- 1.0. Thirty-three eyes treated with 0.4 mg/mL MMC deep in the pocket demonstrated a 38% reduction in IOP from 25.4 +/- 7.9 at baseline to 15.7 +/- 4.6 mmHg at one year. Topical glaucoma medication/patient was reduced 72% from 2.9 +/- 1.0 to 0.8 +/- 1.3. There were no sight-threatening long-term adverse events. CONCLUSION: The InnFocus MicroShunt((r)) is a filtering surgery whose efficacy is related to the location of application and concentration of MMC used. PMID- 26363922 TI - Advances in therapeutics for chronic hepatitis B. AB - Chronic hepatitis B infection remains a major disease burden globally, and leads to high risk of hepatocellular carcinoma development. Current therapies of nucleot(s)ide analogues and interferon alpha treatment remain limited in their efficacy. Several key findings in the hepatitis B virus (HBV) life cycle have led to the development of novel antiviral drugs to inhibit viral replication and persistence. In addition, recent studies on HBV-specific innate and adaptive immune responses have advanced development of immunotherapy to restore immune mediated virus control in chronic hepatitis B patients. In this review, we discuss potential new therapeutic strategies targeting HBV or the host immune system that might lead to a sustained cure for chronic hepatitis B. PMID- 26363924 TI - Gender Differences: A Lifetime Analysis of the Economic Burden of Alzheimer's Disease. AB - BACKGROUND: Gender is one of the best-established differences in risk for Alzheimer's disease (AD) and other forms of dementia, with women being at greater risk. However, the financial implications are unknown. This study aims at understanding the economic burden of AD by gender. METHOD: This study takes a life-time perspective to investigate the burden of AD over the course of the disease. Nationally representative Medicare Current Beneficiary Survey data were used to estimate the course of illness of AD from age 65 to death and the incremental costs of AD on Medicare and Medicaid. Published data on the use and costs of assisted living facilities, home health care, and informal care were imputed into the course of illness to calculate the lifetime costs of these services. RESULTS: Females and males have distinctively different patterns of course of illness of AD. Women face higher risks of having AD (15.5% vs. 13.1%) and of serving as informal caregivers for AD patients (6.8% vs. 4.0%) before death. Medicare and Medicaid account for major payers of AD care for both genders, but the greatest economic challenge of AD to women is the cost of the informal care they deliver, resulting in women bearing six times the cost of men. CONCLUSION: Public policy interventions that aim at curing or slowing the progress of AD will greatly benefit the welfare and economic status of women. PMID- 26363925 TI - Cerebral vasospasm and corticospinal tract injury induced by a modified rat model of subarachnoid hemorrhage. AB - OBJECTIVE: Double-hemorrhage rat models of subarachnoid hemorrhages (SAH) are most effective at simulating delayed cerebral vasospasms (CVS). The present study modified the models to minimize additional trauma and investigated injury of the corticospinal tract (CST) using diffusion tensor imaging (DTI). METHODS: On the first day, 0.3ml of autologous arterial blood was collected by puncturing the caudal artery and injected into the cisterna magna via percutaneous puncture; and the operation was repeated on the third day. The diameters of the basilar artery (BA), middle cerebral artery (MCA), and anterior cerebral artery (ACA) were measured by magnetic resonance angiography on days 3, 5, 7, 9, and 11 post-SAH. Meanwhile, on days 3, 7, 11, 15 and 19, DTI was performed to evaluate the injury of the CST at cerebral peduncle (CP) and pyramidal tract (Py) by measuring fractional anisotropy (FA) value. RESULTS: Blood was deposited mainly in the basal cistern. Diameters of BA, MCA, and ACA were significantly reduced. FA value of the CP was lower in the SAH group than in the control group; but FA value of Py wasn't different between the two groups. CONCLUSION: This is a minimally invasive and high performance rat model of SAH. Additionally, the occurrence of CVS is firm and the axons in CP are injured. PMID- 26363926 TI - The putative acceleration of optic neuritis when combined with chronic hepatitis B. AB - PURPOSE: To review the clinical features of optic neuritis (ON) combined with chronic hepatitis B (CHB) retrospectively. METHOD: Clinical data were reviewed for hospitalized patients diagnosed with isolated ON combined with chronic hepatitis B (CHB-ON) in the Chinese People's Liberation Army General Hospital. The ON diagnosis was confirmed following the criteria of the Optic Neuritis Treatment Trial (ONTT) group. The diagnostic criteria for CHB was serological positivity for hepatitis B surface antigen (HBsAg) for more than 6 months. Other infectious conditions that might lead to bias were excluded. RESULTS: A total of 13 patients (6 female and 7 male, 23 involved eyes) diagnosed with CHB-ON were selected. A total of 12/13 patients presented as atypical ON: 10/13 of the patients exhibited simultaneous or early sequential bilateral eye involvement; 11/13 involved eyes in the acute phase presented with pronounced optic disc edema; and 11/13 patients exhibited corticosteroid resistant. A total of 12/23 affected eyes suffered severe vision loss (<20/200) at the end of the follow-up period, which averaged 13.7 (4-31) months. None of the patients progressed to multiple sclerosis (MS) or neuromyelitis optica (NMO). All blood samples were negative for serological aquaporin 4-antibody using the cell-based assay. CONCLUSIONS: CHB-ON usually presented as the atypical form. Chronic hepatitis B virus infection may lead to the tendency for ON exacerbation. PMID- 26363927 TI - n-3 Polyunsaturated fatty acids inhibit Fc epsilon receptor I-mediated mast cell activation. AB - In vivo models show that n-3 polyunsaturated fatty acids (PUFA) inhibit some of the processes associated with allergic inflammation but the direct effect of n-3 PUFA on mast cells, the major effector cells in allergy, is poorly understood. We sought to determine the effect and mechanism of n-3 PUFA on Fc epsilon receptor I (FcepsilonRI)-mediated signal transduction and mast cell activation. Bone marrow derived mast cells (BMMC) were differentiated from bone marrow obtained from C57BL/6 wild-type (WT) and fat-1 transgenic mice. The fat-1 mice express fatty acid n-3 desaturase and produce endogenous n-3 PUFA. For comparison, exogenous n 3 PUFA were supplemented to WT BMMC and human mast cell (LAD2) cultures. Fat-1 BMMC released less beta-hexosaminidase (beta-hex) and cysteinyl leukotrienes and produced less tumor necrosis factor and chemokine (C-C motif) ligand 2. n-3 PUFA supplementation reduced LAD2 and BMMC degranulation (beta-hex release) following FcepsilonRI activation. Fat-1 BMMC expressed less constitutive Lyn and linker of activated T cells (LAT), and FcepsilonRI-mediated phosphorylation of Lyn, spleen tyrosine kinase and LAT were reduced in fat-1 BMMC. Although the expression of surface and whole cell FcepsilonRI was similar in WT and fat-1 BMMC, unstimulated fat-1 BMMC showed reduced FcepsilonRI localization to lipid rafts, and stimulation with antigen resulted in aberrant FcepsilonRI shuttling to the rafts. Our results show that n-3 PUFA suppress FcepsilonRI-mediated activation of mast cells, which results in reduced mediator release. This effect is associated with a decrease in LAT and Lyn expression as well as abnormal shuttling of FcepsilonRI to lipid rafts. PMID- 26363928 TI - omega-6 (18:2) and omega-3 (18:3) fatty acids in reconstituted high-density lipoproteins show different functionality of anti-atherosclerotic properties and embryo toxicity. AB - Among unsaturated fatty acids, epidemiologic studies have demonstrated that omega 6 (linoleic acid) and omega-3 (linolenic acid) fatty acids show different associations with risk of cardiovascular disease (CVD), although its molecular mechanisms remain unclear. To determine why consumption of omega-3 fatty acid is associated with lower risk of CVD, we investigated the biological functions of omega-6 (linoleic acid) and omega-3 (linolenic acid) in reconstituted HDL (rHDL) after encapsulation using human cells and zebrafish embryo. Apolipoprotein A-I (apoA-I) is the principal protein behind the beneficial functions of HDL, which include potent anti-oxidant, anti-inflammatory, and anti-atherosclerotic activities in blood. Several rHDLs were synthesized with apoA-I and different molar ratio of omega-6 or omega-3 fatty acid. Both fatty acids showed similar solubility in rHDL up to a molar ratio of 95:5:1:10 (palmitoyloleoyl phosphatidylcholine:cholesterol:apoA-I:fatty acid). Although both rHDL showed similar structural properties and alpha-helical contents, omega-6-rHDL showed loss of anti-oxidant ability against LDL oxidation. Uptake of acetylated LDL into macrophages was inhibited by omega-3-rHDL but not omega-6-rHDL, suggesting that omega-6-rHDL has higher pro-atherosclerotic activity. omega-3-rHDL showed more enhanced cholesterol efflux activity with less accumulation of triglyceride in the macrophage. omega-6-rHDL caused more senescence in human dermal fibroblast cells with cytotoxicity, while omega-3-rHDL treatment inhibited the senescence. In zebrafish embryo survivability, omega-3-rHDL-injected embryos showed 86+/-3% survival, whereas omega-6-rHDL-injected ones showed 72+/-2% survival as well as an elevated inflammatory response in zebrafish embryos. In conclusion, omega-6 rHDL and omega-3-rHDL show different physiological activities in atherosclerosis, inflammation, and cellular senescence. PMID- 26363930 TI - Oral Alitretinoin in the Treatment of Severe Refractory Chronic Hand Eczema in the Spanish National Health System: Description and Analysis of Current Clinical Practice. AB - BACKGROUND AND OBJECTIVE: Hand eczema affects nearly 10% of the population. The condition becomes severe and chronic in 5% to 7% of cases and is refractory to topical corticosteroids in 2% to 4%. This study aimed to describe the current use of oral alitretinoin in treating Spanish national health system patients with hand eczema that is refractory to potent topical corticosteroids. MATERIALS AND METHODS: Observational, descriptive, exploratory, cross-sectional study based on the retrospective analysis of records for patients with hand eczema treated with alitretinoin in the Spanish national health system. RESULTS: We reviewed the records for 62 patients in 13 hospitals in 5 different administrative areas (autonomous communities) of Spain. Alitretinoin was usually used at a dosage of 30mg/d. In most cases the physician judged the clinical response to be satisfactory after a single cycle. The recorded adverse effects were foreseeable and of the type reported for systemic retinoids. The dermatologists agreed that the clinical benefits achieved with alitretinoin favored adherence to treatment and an early return to work. CONCLUSIONS: The results show that oral alitretinoin is being used according to established recommendations and that response is good, with few adverse effects. The dermatologists agreed that the benefits favored adherence and improved the patients' health related quality of life. PMID- 26363929 TI - Step-up fecal microbiota transplantation strategy: a pilot study for steroid dependent ulcerative colitis. AB - BACKGROUND: The strategy of using fecal microbiota transplantation (FMT) for refractory ulcerative colitis (UC) remains unclear if single FMT failed to induce remission. This study aimed to evaluate the efficacy and safety of a designed step-up FMT strategy for the steroid-dependent UC. METHODS: Fifteen patients with steroid-dependent UC were enrolled, and treated with step-up FMT strategy. Follow up clinical data was collected for a minimum of 3 months. Fecal microbiota composition before and post FMT of patients and related donors were analyzed by 16S rRNA sequencing. RESULTS: Eight of fourteen (57.1 %) patients achieved clinical improvement and were able to discontinue steroids following step-up FMT. One patient was lost to follow-up. Among the 8 patients who responded, five (35.7 %) received one FMT therapy, one (7.1 %) received two FMTs, and two (14.2 %) received two FMTs plus a scheduled course of steroids. Four (28.6 %) of the 8 patients who responded maintained long-term remission during follow-up (3-18 months). Six patients (42.9 %) failed to meet the criteria of clinical improvement and maintained steroid dependence, though three experienced transient or partial improvement. Microbiota analysis showed that FMT altered the composition greatly, and a microbiota composition highly similar to that of the donor emerged in the patients with successful treatment. No severe adverse events occurred during treatment and follow-up. CONCLUSIONS: Step-up FMT strategy shows promise as a therapeutic strategy for patients with steroid-dependent UC, likely due to the successful restructuring of gut microbial composition. TRIAL REGISTRATION: ClinicalTrials.gov, Number NCT01790061. PMID- 26363931 TI - Cutaneous metastases on the head and neck from a papillary thyroid carcinoma, follicular variant. PMID- 26363934 TI - Creating Conditions for Effective Nutrition Education. PMID- 26363935 TI - Weighing in on Weight. PMID- 26363933 TI - Facility- and Patient-Level Factors Associated with Esophageal Variceal Screening in the USA. AB - BACKGROUND AND AIM: The American Association for the Study of Liver Disease (AASLD) recommends screening for esophageal varices (EV) by esophagoduodenoscopy (EGD) in patients with cirrhosis to guide decisions regarding primary prophylaxis for EV hemorrhage. We aimed to identify patient and facility factors associated with EV screening in veterans with hepatitis C (HCV)-associated cirrhosis. METHODS: This was a population-based cohort study. Veterans with HCV and newly diagnosed cirrhosis between 1/1/2004 and 12/31/2005 and followed until 12/31/2011 were included. The primary outcome was receipt of EGD within 1 year of cirrhosis diagnosis. Patient- and facility-level factors associated with EV screening were determined. RESULTS: A total of 4230 patients with HCV cirrhosis were identified. During median follow-up of 6.1 years (IQR: 4.0-8.0), 21.5 % developed a decompensating event, and 38.3 % died. Fifty-four percent received an EGD, and 33.8 % had an EGD within guidelines. Median time from cirrhosis diagnosis to EGD was 72 days (IQR: 12-176). Factors independently associated with receipt of EV screening were a decompensation event (OR 1.16, CI 1.01-1.32) and gastroenterology/hepatology clinic access (OR 2.1, CI 1.73-2.46), whereas cardiovascular (OR 0.81, CI 0.69-0.95), mental health (OR 0.79, CI 0.68-0.91), and respiratory (OR 0.85, CI 0.72-0.99) comorbidities were associated with reduced likelihood of EV screening. CONCLUSION: EV screening per AASLD guidelines occurs in only one-third of patients. This missed opportunity was strongly associated with access to gastroenterology/hepatology specialty care. Additionally, providers may be relying on clinical cues (i.e., decompensation) to prompt referral for endoscopy suggesting education to improve compliance with guidelines is needed. PMID- 26363932 TI - Current Approaches to Quantifying Tonic and Reflex Autonomic Outflows Controlling Cardiovascular Function in Humans and Experimental Animals. AB - The role of the autonomic nervous system in the pathophysiology of human and experimental models of cardiovascular disease is well established. In the recent years, there have been some rapid developments in the diagnostic approaches used to assess and monitor autonomic functions. Although most of these methods are devoted for research purposes in laboratory animals, many have still found their way to routine clinical practice. To name a few, direct long-term telemetry recording of sympathetic nerve activity (SNA) in rodents, single-unit SNA recording using microneurography in human subjects and spectral analysis of blood pressure and heart rate in both humans and animals have recently received an overwhelming attention. In this article, we therefore provide an overview of the methods and techniques used to assess tonic and reflex autonomic functions in humans and experimental animals, highlighting current advances available and procedure description, limitations and usefulness for diagnostic purposes. PMID- 26363936 TI - Eating Disorders and Associated Health Risks Among University Students. AB - OBJECTIVE: To determine the prevalence of eating disorders among university students and its relationship to behavioral characteristics and substance use. DESIGN: Cross-sectional study collected socioeconomic characteristics and behavioral risk. SETTING: University of Upper Normandy, France. PARTICIPANTS: University student volunteers. PHENOMENON OF INTEREST: The Sick, Control, One stone, Fat, Food (SCOFF) screening test was used to identify subjects with eating disorders by a confidential questionnaire self-administered either online or on paper. ANALYSIS: Multivariate logistic regression models with P < .05 considered significant. RESULTS: A total of 3,457 students were included with a male-to female ratio of 0.57. The prevalence of positive SCOFF screening was 20.5% among students. A positive relation between the positive SCOFF was observed with female gender (adjusted odds ratio [AOR], 2.98; 95% confidence interval [CI], 2.28-3.89; P < .001), stress (AOR, 1.10; 95% CI, 1.09-1.12; P < .001), depression (AOR, 8.62; 95% CI, 3.37-22.10; P < .001) alcohol abuse problems (AOR, 1.52; 95% CI, 1.20-1.95; P = .006), and risk of cyber-addiction (AOR, 5.09; 95% CI, 2.69-9.62; P < .001). CONCLUSIONS AND IMPLICATIONS: Eating disorders are highly prevalent among university students in France and associated with other behavior risks, stress, and depression. It might prove necessary in the future to screen students with the SCOFF questionnaire upon entry to the university to inform student about the risk of eating disorders and advise them to consult with their general practitioner. PMID- 26363937 TI - Test-Retest Reliability of the National Health and Nutrition Examination Survey's 5-Item Food Insecurity Questionnaire Completed by Fourth-Grade Children. AB - OBJECTIVE: To examine test-retest reliability and internal consistency of a 5 item food insecurity questionnaire used in the National Health and Nutrition Examination Survey (NHANES). METHODS: Researchers administered NHANES's questionnaire in the classroom to 92 fourth-grade children (74 African American; 48 girls) in 2 sessions 27-30 days apart in spring, 2011. Each classroom administration lasted 5-10 minutes. RESULTS: Test-retest reliability was 0.66 (Kendall tau), which is modest. Internal consistency (Cronbach alpha) was .67 and .70 for respective administrations. Food insecurity scores were related to gender (adjusted P = .05) and academic achievement (adjusted P = .004) but not to socioeconomic status or body mass index percentile (binomial regression). On average, boys reported higher food insecurity than girls. Children with lower academic achievement scores reported higher food insecurity than children with higher academic achievement scores. CONCLUSIONS AND IMPLICATIONS: NHANES's 5-item questionnaire may be group administered to assess food insecurity efficiently as reported by individual fourth-grade children. PMID- 26363938 TI - An Entertainment-Based Approach to Promote Fruits and Vegetables to Young Children. PMID- 26363939 TI - Indications and Outcomes of Osteoporosis and Bone Modulation Therapies. AB - Osteoporosis is a disorder of bone strength that leads to an increased risk of fractures. It is most commonly seen in patients aged 50 or older, although it can sometimes occur at a younger age if there are other comorbidities present. The most common cause of osteoporosis by far is menopause, although it also occurs in men, usually with higher morbidity rates than those seen in women. There are many treatment options available, such as anabolics and antiresorptives, with many more currently being developed. However, osteoporosis remains grossly unrecognized and untreated, resulting in a significant strain on the American economy. PMID- 26363940 TI - Patent ductus arteriosus occlusion in small dogs utilizing a low profile Amplatz(r) canine duct occluder prototype. AB - OBJECTIVES: To develop procedural methodology and assess the safety, utility and effectiveness of a low profile Amplatz((r)) canine duct occluder (ACDO) prototype in dogs deemed too small to undergo ductal occlusion with the commercially available ACDO device. ANIMALS: Twenty-one dogs with left-to-right shunting patent ductus arteriosus (PDA). Dogs were >=1.5 kg but considered too small to accommodate a 6 Fr catheter or 4 Fr sheath within the femoral artery. METHODS: Prospective canine study using a low profile ACDO prototype delivered through a 4 Fr catheter via a femoral arterial approach. Procedural methods, fluoroscopy time, perioperative complications, and residual ductal flow were evaluated, and angiographic ductal morphology and dimensions were tabulated. RESULTS: All 21 dogs underwent successful ductal occlusion using the prototype device, 4 Fr catheter, and right femoral artery approach. No perioperative complications or device embolization occurred. The median minimal ductal diameter was 1.9 mm (range, 0.4-3.4), and the median device size deployed was 4 mm (range, 3-6). Complete ductal occlusion was noted in 17 dogs (81%) on post-deployment angiography. Twenty dogs (95%) had no residual flow on echocardiography performed the following day. In the 17 dogs (81%) that returned for a long-term (>=3months) follow-up evaluation, all had complete ductal occlusion based on echocardiography. CONCLUSIONS: The low profile ACDO prototype is a safe and effective method of PDA occlusion in the small dog. The deployment procedure appears of similar technical difficulty to the commercially available ACDO. PMID- 26363941 TI - Prevalence of congenital heart disease in 76,301 mixed-breed dogs and 57,025 mixed-breed cats. AB - OBJECTIVE: Assess the prevalence of congenital heart disease (CHD) in a large population of mixed-breed dogs and cats. ANIMALS: 76,301 mixed-breed dogs and 57,025 mixed-breed cats. METHODS: Retrospective review of records and examinations based on specified diagnostic criteria. RESULTS: Among mixed-breed dogs, the prevalence of CHD was 0.13% (51.4% female) and of innocent murmurs was 0.10% (53.0% male). Pulmonic stenosis was the most common defect followed by patent ductus arteriosus, aortic stenosis, and ventricular septal defect. Among mixed-breed cats, prevalence of CHD was 0.14% (55.2% male) and of innocent murmurs was 0.16% (54.4% male). When the 25 cats with dynamic left or right ventricular outflow obstruction were counted with cases of innocent murmurs, the overall prevalence was 0.2%. Ventricular septal defects were the most common feline CHD followed closely by aortic stenosis and hypertrophic obstructive cardiomyopathy. There was no overall sex predilection for CHD in mixed-breed cats or dogs, and no significant difference in CHD prevalence between cats or dogs. Among dogs, subvalvular aortic stenosis and mitral valve dysplasia had a male predisposition while patent ductus arteriosus had a female predisposition. Among cats, valvular pulmonic stenosis, subvalvular and valvular aortic stenosis, and ventricular septal defects had a male predisposition while pulmonary artery stenosis had a female predisposition. CONCLUSIONS: The prevalence of CHD in a mixed-breed dogs and cats is lower than for prior studies, perhaps due to the lack of purebreds in the study population or actual changes in disease prevalence. PMID- 26363942 TI - Calcium, phosphorus, and bone metabolism in the fetus and newborn. AB - The placenta actively transports minerals whereas the intestines and kidneys may be nonessential for fetal mineral homeostasis. Mineral concentrations are higher in fetal blood than in adults in order for the developing skeleton to accrete adequate mineral content. Fetal bone development and serum mineral regulation are dependent upon parathyroid hormone (PTH) and PTH-related protein (PTHrP), but not calcitriol, fibroblast growth factor-23, calcitonin, or the sex steroids. After birth, a switch from fetal to neonatal regulatory mechanisms is triggered by loss of the placental calcium infusion, onset of a breathing, and a postnatal fall in serum calcium and rise in phosphorus. This is followed by an increase in PTH, then a rise in calcitriol, and developmental changes in kidneys and intestines. Serum calcium increases and phosphorus declines over days. The intestines become the main source of mineral, while kidneys reabsorb mineral, and bone turnover contributes additional mineral to the circulation. PMID- 26363943 TI - Development of a liquid chromatography-electrospray ionization-tandem mass spectrometry method for the simultaneous analysis of intact glucosinolates and isothiocyanates in Brassicaceae seeds and functional foods. AB - A new high pressure liquid chromatography-electrospray ionization-tandem mass spectrometry method for the simultaneous determination of glucosinolates, as glucoraphanin and glucoerucin, and the corresponding isothiocyanates, as sulforaphane and erucin, was developed and applied to quantify these compounds in Eruca sativa defatted seed meals and enriched functional foods. The method involved solvent extraction, separation was achieved in gradient mode using water with 0.5% formic acid and acetonitrile with 0.5% formic acid and using a reverse phase C18 column. The electrospray ion source operated in negative and positive mode for the detection of glucosinolates and isothiocyanates, respectively, and the multiple reaction monitoring (MRM) was selected as acquisition mode. The method was validated following the ICH guidelines. Replicate experiments demonstrated a good accuracy (bias%<10%) and precision (CV%<10%). Detection limits and quantification limits are in the range of 1-400ng/mL for each analytes. Calibration curves were validated on concentration ranges from 0.05 to 50MUg/mL. The method proved to be suitable for glucosinolates and isothiocyanates determination both in biomasses and in complex matrices such as food products enriched with glucosinolates, or nutraceutical bakery products. In addition, the developed method was applied to the simultaneous determination of glucosinolates and isothiocyanates in bakery product enriched with glucosinolates, to evaluate their thermal stability after different industrial processes from cultivation phases to consumer processing. PMID- 26363944 TI - A straightforward methodology for designing continuous monoclonal antibody capture multi-column chromatography processes. AB - A simple process development strategy for continuous capture multi-column chromatography (MCC) is described. The approach involves a few single column breakthrough experiments, based on several simplifying observations that enable users to rapidly convert batch processes into well-designed multi-column processes. The method was validated using a BioSMB((r)) (Pall Life Sciences) lab scale multi-column system and a mAb capture process employing Protein A resin. The approach enables users to optimize MCC processes based on their internal preferences and constraints without requiring any mathematical modeling expertise. PMID- 26363945 TI - Using active flow technology columns for high through-put and efficient analyses: The drive towards ultra-high through-put high-performance liquid chromatography with mass spectral detection. AB - The performance of active flow technology chromatography columns in parallel segmented flow mode packed with 5 MUm Hypersil GOLD particles was compared to conventional UHPLC columns packed with 1.9 MUm Hypersil GOLD particles. While the conventional UHPLC columns produced more theoretical plates at the optimum flow rate, when separations were performed at maximum through-put the larger particle size AFT column out-performed the UHPLC column. When both the AFT column and the UHPLC column were operated such that they yielded the same number of theoretical plates per separation, the separation on the AFT column was twice as fast as that on the UHPLC column, with the same level of sensitivity and at just 70% of the back pressure. Furthermore, as the flow velocity further increased the performance gain on the AFT column compared to the UHPLC column improved. An additional advantage of the AFT column was that the flow stream at the exit of the column was split in the radial cross section of the peak profile. This enables the AFT column to be coupled to a flow limiting detector, such as a mass spectrometer. When operated under high through-put conditions separations as fast as six seconds, using mobile phase flow rates in the order of 5-6 mL/min have been recorded. PMID- 26363946 TI - The evolution of analytical chemistry methods in foodomics. AB - The methodologies of food analysis have greatly evolved over the past 100 years, from basic assays based on solution chemistry to those relying on the modern instrumental platforms. Today, the development and optimization of integrated analytical approaches based on different techniques to study at molecular level the chemical composition of a food may allow to define a 'food fingerprint', valuable to assess nutritional value, safety and quality, authenticity and security of foods. This comprehensive strategy, defined foodomics, includes emerging work areas such as food chemistry, phytochemistry, advanced analytical techniques, biosensors and bioinformatics. Integrated approaches can help to elucidate some critical issues in food analysis, but also to face the new challenges of a globalized world: security, sustainability and food productions in response to environmental world-wide changes. They include the development of powerful analytical methods to ensure the origin and quality of food, as well as the discovery of biomarkers to identify potential food safety problems. In the area of nutrition, the future challenge is to identify, through specific biomarkers, individual peculiarities that allow early diagnosis and then a personalized prognosis and diet for patients with food-related disorders. Far from the aim of an exhaustive review of the abundant literature dedicated to the applications of omic sciences in food analysis, we will explore how classical approaches, such as those used in chemistry and biochemistry, have evolved to intersect with the new omics technologies to produce a progress in our understanding of the complexity of foods. Perhaps most importantly, a key objective of the review will be to explore the development of simple and robust methods for a fully applied use of omics data in food science. PMID- 26363947 TI - Automated dynamic hollow fiber liquid-liquid-liquid microextraction combined with capillary electrophoresis for speciation of mercury in biological and environmental samples. AB - A simple home-made automatic dynamic hollow fiber based liquid-liquid-liquid microextraction (AD-HF-LLLME) device was designed and constructed for the simultaneous extraction of organomercury and inorganic mercury species with the assistant of a programmable flow injection analyzer. With 18-crown-6 as the complexing reagent, mercury species including methyl-, ethyl-, phenyl- and inorganic mercury were extracted into the organic phase (chlorobenzene), and then back-extracted into the acceptor phase of 0.1% (m/v) 3-mercapto-1-propanesulfonic acid (MPS) aqueous solution. Compared with automatic static (AS)-HF-LLLME system, the extraction equilibrium of target mercury species was obtained in shorter time with higher extraction efficiency in AD-HF-LLLME system. Based on it, a new method of AD-HF-LLLME coupled with large volume sample stacking (LVSS)-capillary electrophoresis (CE)/UV detection was developed for the simultaneous analysis of methyl-, phenyl- and inorganic mercury species in biological samples and environmental water. Under the optimized conditions, AD-HF-LLLME provided high enrichment factors (EFs) of 149-253-fold within relatively short extraction equilibrium time (25min) and good precision with RSD between 3.8 and 8.1%. By combining AD-HF-LLLME with LVSS-CE/UV, EFs were magnified up to 2195-fold and the limits of detection (at S/N=3) for target mercury species were improved to be sub ppb level. PMID- 26363948 TI - Determination of imidazole derivatives by micellar electrokinetic chromatography combined with solid-phase microextraction using activated carbon-polymer monolith as adsorbent. AB - In this study, an effective method for the separation of imidazole derivatives 2 methylimidazole (2-MEI), 4- methylimidazole (4-MEI) and 2-acetyl-4 tetrahydroxybutylimidazole (THI) in caramel colors using cation-selective exhaustive injection and sweeping micellar electrokinetic chromatography (CSEI sweeping-MEKC) was developed. The limits of detection (LOD) and quantitation (LOQ) for the CSEI-sweeping-MEKC method were in the range of 4.3-80MUgL(-1) and 14-270MUgL(-1), respectively. Meanwhile, a rapid fabrication activated carbon polymer (AC-polymer) monolithic column as adsorbent for solid-phase microextraction (SPME) of imidazole colors was developed. Under the optimized SPME condition, the extraction recoveries for intra-day, inter-day and column-to column were in the range of 84.5-95.1% (<6.3% RSDs), 85.6-96.1% (<4.9% RSDs), and 81.3-96.1% (<7.1% RSDs), respectively. The LODs and LOQs of AC-polymer monolithic column combined with CSEI-sweeping-MEKC method were in the range of 33.4 60.4MUgL(-1) and 111.7-201.2MUgL(-1), respectively. The use of AC-polymer as SPME adsorbent demonstrated the reduction of matrix effect in food samples such as soft drink and alcoholic beverage thereby benefiting successful determination of trace-level caramel colors residues using CSEI-sweeping-MEKC method. The developed AC-polymer monolithic column can be reused for more than 30 times without any significant loss in the extraction recovery for imidazole derivatives. PMID- 26363949 TI - Determination of dyes in cosmetic products by micro-matrix solid phase dispersion and liquid chromatography coupled to tandem mass spectrometry. AB - A simple method based on micro-matrix solid phase dispersion (MSPD) followed by liquid chromatography-mass spectrometry (LC-MS/MS) has been developed for the rapid and simultaneous determination of nine regulated water-soluble dyes in personal care and decorative products. The proposed miniaturized extraction procedure was optimized by means of experimental designs in order to obtain the highest extraction efficiency. Under the optimal selected conditions, the method was validated showing satisfactory performance in terms of linearity, sensitivity, and intra-day and inter-day precision. Recoveries were evaluated in different cosmetic matrices and they can be considered quantitative with average values between 70 and 120% with relative standard deviations (RSD) lower than 15%. Finally, the validated method was applied to 24 samples of cosmetic and personal care products, including decorative makeup, lipsticks, lip gloss, toothpastes, regenerating creams, shampoos, and eye shadows, among others, to cover a broad range of commercial real samples. Seven of the analyzed dyes were detected, being declared all of them in the label list of ingredients. More than 50% of the samples contained at least two dyes. Tartrazine was the most frequently found (50% of the samples) at concentration levels of 0.243-79.9MUgg( 1). Other targets were found in 1-9 samples, highlighting the presence of Quinoline at high concentration (>500MUgg(-1)) in a toothpaste sample. PMID- 26363950 TI - Matrix effects in human urine analysis using multi-targeted liquid chromatography tandem mass spectrometry. AB - Different sample preparation methods were tested for human urine for the subsequent analysis with a LC-MS/MS multimethod to quantify 65 micropollutants (pesticides, pharmaceuticals, personal care products, industrial chemicals and metabolites) within the general population. Direct injection of diluted urine revealed highly variable and often severe signal suppression for nearly all analytes at relevant concentration levels during electrospray ionization. Urine samples were highly variable in their total organic carbon (500-10,000mgL(-1)) and creatinine (0.35-13mM) content as well as in electrical conductivity (3 19mScm(-1)) but these differences did not correlate clearly with the strength of matrix effects. Therefore, matrix removal by solid phase extraction was intended and different mixed-mode sorbents were tested. Results showed poor apparent recoveries likely due to insufficient separation of target analytes and matrix compounds for all tested sorbents. The wide variability and high concentration levels of urine constituents strongly affect electrospray ionization as well as recovery during extraction at the sub-microgram per liter level. Especially, the hydrophobic interaction at the hydrophilic-lipophilic-balanced sorbent was affected. It is concluded that the urine matrix is too strong, too diverse and too variable to allow one sample preparation method for the very diverse analytes of a LC-MS/MS multimethod. Instead dedicated methods appear more promising. PMID- 26363952 TI - [The chatting gathering, a new type of learning session in primary care]. PMID- 26363951 TI - High resolution mass spectrometry for quantitative analysis and untargeted screening of algal toxins in mussels and passive samplers. AB - Measurement of marine algal toxins has traditionally focussed on shellfish monitoring while, over the last decade, passive sampling has been introduced as a complementary tool for exploratory studies. Since 2011, liquid chromatography tandem mass spectrometry (LC-MS/MS) has been adopted as the EU reference method (No. 15/2011) for detection and quantitation of lipophilic toxins. Traditional LC MS approaches have been based on low-resolution mass spectrometry (LRMS), however, advances in instrument platforms have led to a heightened interest in the use of high-resolution mass spectrometry (HRMS) for toxin detection. This work describes the use of HRMS in combination with passive sampling as a progressive approach to marine algal toxin surveys. Experiments focused on comparison of LRMS and HRMS for determination of a broad range of toxins in shellfish and passive samplers. Matrix effects are an important issue to address in LC-MS; therefore, this phenomenon was evaluated for mussels (Mytilus galloprovincialis) and passive samplers using LRMS (triple quadrupole) and HRMS (quadrupole time-of-flight and Orbitrap) instruments. Matrix-matched calibration solutions containing okadaic acid and dinophysistoxins, pectenotoxin, azaspiracids, yessotoxins, domoic acid, pinnatoxins, gymnodimine A and 13 desmethyl spirolide C were prepared. Similar matrix effects were observed on all instruments types. Most notably, there was ion enhancement for pectenotoxins, okadaic acid/dinophysistoxins on one hand, and ion suppression for yessotoxins on the other. Interestingly, the ion selected for quantitation of PTX2 also influenced the magnitude of matrix effects, with the sodium adduct typically exhibiting less susceptibility to matrix effects than the ammonium adduct. As expected, mussel as a biological matrix, quantitatively produced significantly more matrix effects than passive sampler extracts, irrespective of toxin. Sample dilution was demonstrated as an effective measure to reduce matrix effects for all compounds, and was found to be particularly useful for the non-targeted approach. Limits of detection and method accuracy were comparable between the systems tested, demonstrating the applicability of HRMS as an effective tool for screening and quantitative analysis. HRMS offers the advantage of untargeted analysis, meaning that datasets can be retrospectively analyzed. HRMS (full scan) chromatograms of passive samplers yielded significantly less complex data sets than mussels, and were thus more easily screened for unknowns. Consequently, we recommend the use of HRMS in combination with passive sampling for studies investigating emerging or hitherto uncharacterized toxins. PMID- 26363953 TI - [Health surveillance for early detection of burnout in primary care physicians syndrome]. PMID- 26363954 TI - [Relationship between perceived emotional intelligence and professional quality of life with the achievement of occupational objectives in the costa del sol primary health care district]. AB - OBJECTIVE: To examine the relationship between "Quality of Professional Life" and "Perceived Emotional Intelligence" and the relationship of both of these with the level of achievement of occupational objectives in the Costa del Sol Primary Health Care District. DESIGN: Multicentre descriptive cross-sectional observational study. LOCATION: The Costa del Sol Primary Health Care District in the province of Malaga. PARTICIPANTS: Sample of Employees of all categories in fixed and contracted employment in the Management Units of the Costa del Sol District. (N=303). Respondents 247 (81.5%) PRINCIPAL MEASUREMENTS: The data collected was that of the percentage of achievement of objectives in 2010 and the socio-demographic data of the participants, using ad hoc designed self-report questionnaires. The TMMS -24 questionnaire was used to measure the "Perceived Emotional Intelligence", with the following dimensions: Perception, comprehension, and emotional control, and the CVP-35 measuring: management support, work demands, and intrinsic motivation. RESULTS: Significant correlationas were observed between Quality of Professional Life and Emotional Intelligence in the Regulation (p<.01) and Comprehension categories (p<0.05). There were also significant correlations between the profession and the type of contract in the achievement of objectives (p<.005), and quality of professional life and type of contract (p<.05). CONCLUSIONS: The perceived quality of professional life is related to perception and regulation dimensions of Emotional Intelligence. Knowledge of emotion management methods should be promoted by management organisations for all employees. PMID- 26363955 TI - [Differences and similarities of primary care in the German and Spanish health care systems]. AB - An efficient primary care is of particular importance for any countries' health care system. Many differences exist on how distinctive countries try to obtain the goal of an efficient, cost-effective primary care for its population. In this article we conducted a selective literature review, which includes both scientific and socio-political publications. The findings are complemented with the experience of a Spanish physician from Seville in her last year of training in family medicine, who completed a four months long rotation in the German health care system. We highlighted different features by comparing both countries, including their health care expenditure, the relation between primary and secondary care, the organization in the academic field and the training of future primary care physicians. It is clear that primary care in both countries plays a central role, have to deal with shortcomings, and in some points one system can learn from the other. PMID- 26363956 TI - [PERSIRIS study: observational study, postmarketing, prospective, to evaluate the persistence to treatment with monthly risedronate in women with osteoporosis]. AB - OBJECTIVE: To assess the persistence of treatment with monthly risedronate and know the reasons of persistence and nontherapeutic persistence and the profile of the non-persistent patients. DESING: Observational, postmarketin and prospective study. LOCATION: Primary care, traumatology, rheumatology, gynecology and geriatrics of Catalonia. PARTICIPANTS: Women with osteoporosis treated with monthly risedronate that previously had abandoned weekly bisphosphonate therapy. MAIN MEASUREMENTS: Percentage of patients on persistent monthly risedronate year of their prescription, reasons for persistent and non persistent and profile of non persistent patients in relation to biodemographic data, clinical data and risk factors for fracture. RESULTS: 289 evaluable patients with a mean age of 68.3. At 12 months of initiation with monthly risedronate, 58.1% of patients remained on treatment. Most frequent reasons for leaving: fear of having side effects and belief that the disease is typical of the age. Reasons remarkable persistence: comfort/ease and dosage. Significant differences were observed between persistent and non-persistent patients relative to: employment status, number of concomitant therapy and height; however the results of possible associated factors must be contextualized within the study characteristics and the difference in size does not seem clinically relevant. CONCLUSIONS: The administration of therapeutic patterns more comfortable as monthly risedronate in osteoporosis, could facilitate persistence in patients improving the effectiveness of the drug. However in that persistence can also influence biodemographic and clinical variables and diverse of various kinds. PMID- 26363957 TI - Outcomes of a Comprehensive Youth Program for HIV-infected Adolescents in Thailand. AB - We developed an intervention program for HIV-infected Thai adolescents with two group sessions and two individual sessions, focusing on four strategies: health knowledge, coping skills, sexual risk reduction, and life goals. An audio computer-assisted self-interview (ACASI) was administered to assess knowledge, attitudes, and practices (KAP) regarding antiretroviral therapy management, reproductive health, and HIV-associated risk behavior. The program was implemented in two HIV clinics; 165 (84%) adolescents (intervention group) participated in the program; 32 (16%) completed the ACASI without participating in the group or individual sessions (nonintervention group). The median age was 14 years, and 56% were female. Baseline KAP scores of the intervention and nonintervention groups were similar. Two months after the intervention, knowledge and attitude scores increased (p < .01) in the intervention group, and the increase was sustained at 6 months. KAP scores did not change from baseline in the nonintervention group at 6 or 12 months after enrollment. PMID- 26363958 TI - Transcriptomic Analyses on the Role of Nitric Oxide in Plant Disease Resistance. AB - Nitric oxide (NO) is a gaseous molecule having key roles in many physiological processes such as germination, growth, development and senescence. It has been also shown the important role of NO as a signaling molecule in the response to a wide variety of stress situations, including both biotic and abiotic stress conditions. In the last few years, a growing number of studies have focused on NO cell targets by several approaches such as transcriptomic and proteomic analyses. This review is centered on offering an update about the principal medium- and large-scale transcriptomic analyses performed with several NO donors including microarray, cDNA-amplification fragment length polymorphism (AFLP) and high throughput sequencing (RNA-seq technology) approaches mainly focused on the role of this reactive nitrogen species in relation to plant disease resistance. Different putative NO-responsive genes have been identified in different plant tissues and plant species by application of several NO donors suggesting the implication of NO-responsive genes with plant adaptive responses to biotic stress processes. Finally, it is also provided an overview about common transcription factor-binding sites of NO-responsive genes and the need to further analyze the different NO-targets by other omics studies. PMID- 26363960 TI - Fuzzy wavelet plus a quantum neural network as a design base for power system stability enhancement. AB - In this study, we introduce an indirect adaptive fuzzy wavelet neural controller (IAFWNC) as a power system stabilizer to damp inter-area modes of oscillations in a multi-machine power system. Quantum computing is an efficient method for improving the computational efficiency of neural networks, so we developed an identifier based on a quantum neural network (QNN) to train the IAFWNC in the proposed scheme. All of the controller parameters are tuned online based on the Lyapunov stability theory to guarantee the closed-loop stability. A two-machine, two-area power system equipped with a static synchronous series compensator as a series flexible ac transmission system was used to demonstrate the effectiveness of the proposed controller. The simulation and experimental results demonstrated that the proposed IAFWNC scheme can achieve favorable control performance. PMID- 26363961 TI - Investigation on Amari's dynamical neural field with global constant inhibition. AB - In this paper, the properties of Amari's dynamical neural field with global constant inhibition induced by its kernel are investigated. Amari's dynamical neural field illustrates many neurophysiological phenomena successfully and has been applied to unsupervised learning like data clustering in recent years. In its applications, the stationary solution to Amari's dynamical neural field plays an important role that the underlying patterns being perceived are usually presented as the excited region in it. However, the type of stationary solution to dynamical neural field with typical kernel is often sensitive to parameters of its kernel that limits its range of application. Different from dynamical neural field with typical kernel that have been discussed a lot, there are few theoretical results on dynamical neural field with global constant inhibitory kernel that has already shown better performance in practice. In this paper, some important results on existence and stability of stationary solution to dynamical neural field with global constant inhibitory kernel are obtained. All of these results show that such kind of dynamical neural field has better potential for missions like data clustering than those with typical kernels, which provide a theoretical basis of its further extensive application. PMID- 26363959 TI - Rho GTPase signalling in cell migration. AB - Cells migrate in multiple different ways depending on their environment, which includes the extracellular matrix composition, interactions with other cells, and chemical stimuli. For all types of cell migration, Rho GTPases play a central role, although the relative contribution of each Rho GTPase depends on the environment and cell type. Here, I review recent advances in our understanding of how Rho GTPases contribute to different types of migration, comparing lamellipodium-driven versus bleb-driven migration modes. I also describe how cells migrate across the endothelium. In addition to Rho, Rac and Cdc42, which are well known to regulate migration, I discuss the roles of other less-well characterized members of the Rho family. PMID- 26363962 TI - The Power of Omics to Identify Plant Susceptibility Factors and to Study Resistance to Root-knot Nematodes. AB - Technology has contributed to the advances on the genomic, transcriptomic, metabolomic and proteomic analyses of the plant-root-knot nematode (RKN) interaction. Holistic approaches to obtain expression profiles, such as cDNA libraries, differential display, q-PCR, microarray hybridization, massive sequencing, etc., have increased our knowledge on the molecular aspects of the interaction and have triggered the development of biotechnological tools to control this plague. An important limitation, however, has been the difficulty of cross-comparative analysis of these data. The construction of a database, NEMATIC, compiling microarray data available in Arabidopsis of the interaction with plant endoparasitic nematodes facilitated the in silico analysis, but is not sufficient for the handling of 'omic' information of different plant species. Omics combined with cell isolation techniques have shed some light on the heterogeneous expression signatures of nematode induced gall tissues, i.e., plant defences are specifically inhibited in giant cells within the gall aiding the nematode for a successful establishment. The natural resistance against RKNs varies from an early hypersensitive reaction before the establishment of the nematode, to the arrest of gall growth. The molecular bases of these mechanisms, not fully understood yet, could disclose powerful targets for the development of biotechnology based tools for nematode control. PMID- 26363964 TI - Emotional intelligence training: A necessity for nursing education curriculum. PMID- 26363963 TI - Capturing readiness to learn and collaboration as explored with an interprofessional simulation scenario: A mixed-methods research study. AB - BACKGROUND: Didactic lecture does not lend itself to teaching interprofessional collaboration. High-fidelity human patient simulation with a focus on clinical situations/scenarios is highly conducive to interprofessional education. Consequently, a need for research supporting the incorporation of interprofessional education with high-fidelity patient simulation based technology exists. OBJECTIVES: The purpose of this study was to explore readiness for interprofessional learning and collaboration among pre-licensure health professions students participating in an interprofessional education human patient simulation experience. METHODS: Using a mixed methods convergent parallel design, a sample of 53 pre-licensure health professions students enrolled in nursing, respiratory therapy, health administration, and physical therapy programs within a college of health professions participated in high-fidelity human patient simulation experiences. Perceptions of interprofessional learning and collaboration were measured with the revised Readiness for Interprofessional Learning Scale (RIPLS) and the Health Professional Collaboration Scale (HPCS). Focus groups were conducted during the simulation post-briefing to obtain qualitative data. Statistical analysis included non-parametric, inferential statistics. Qualitative data were analyzed using a phenomenological approach. RESULTS: Pre- and post-RIPLS demonstrated pre-licensure health professions students reported significantly more positive attitudes about readiness for interprofessional learning post-simulation in the areas of team work and collaboration, negative professional identity, and positive professional identity. Post-simulation HPCS revealed pre-licensure nursing and health administration groups reported greater health collaboration during simulation than physical therapy students. Qualitative analysis yielded three themes: "exposure to experiential learning," "acquisition of interactional relationships," and "presence of chronology in role preparation." Quantitative and qualitative data converged around the finding that physical therapy students had less positive perceptions of the experience because they viewed physical therapy practice as occurring one-on-one rather than in groups. CONCLUSION: Findings support that pre-licensure students are ready to engage in interprofessional education through exposure to an experiential format such as high-fidelity human patient simulation. PMID- 26363965 TI - Myotonia-like symptoms in a patient with spinal and bulbar muscular atrophy. AB - We describe the case of a 33-year-old man with a 4-year history of worsening muscle stiffness and weakness in his right hand. He showed elevated serum creatine kinase levels at the onset of muscle stiffness that was characterized by delayed muscle relaxation after voluntary contraction. This symptom often occurred during cold exposure, and was partially attenuated by sodium channel blockade. Electrodiagnostic findings in repetitive nerve stimulation, short exercise, and cooling tests were normal. Electromyography showed chronic denervation potentials in his cranial, cervical, thoracic, and lumbosacral myotomes without myotonic discharge. He exhibited facial and tongue fasciculations, hypernasality, gynecomastia, neurogenic changes in muscle biopsy, and increased serum testosterone levels. Spinal and bulbar muscular atrophy (SBMA) was diagnosed on the basis of the CAG trinucleotide expansion in the gene coding androgen receptor. A myotonia-like symptom without myotonic discharge may present as an early neurological sign of SBMA, which possibly reflects a sodium channel dysfunction in skeletal muscles. PMID- 26363966 TI - Congenital myasthenic syndrome due to mutation in CHRNE gene with clinical worsening and thymic hyperplasia attributed to association with autoimmune myasthenia gravis. AB - We report a patient with congenital myasthenic syndrome (CMS) due to mutation in CHRNE with symptoms since the age of 4; mild to moderate fatigable weakness involved mainly ocular, bulbar and limb muscles; functional impact of the disease in their development and physical activity was modest. By the age of 34, the patient experienced gradual worsening of fatigue with dyspnoea and pronounced limb weakness, requiring significant increase of pyridostigmine. Further, a remarkable and sustained clinical improvement followed thymectomy with hyperplastic thymus. Despite of the absence of detectable antibodies to acetyl choline receptor (AChR) (including clustered-AChR), muscle-specific kinase and low-density lipoprotein receptor-related protein-4 antibodies in the serum obtained nine years after thymectomy, the clinical, genetic and histological features are in keeping with the extremely rare association of two rare neuromuscular junction disorders - CMS and myasthenia gravis (MG). The inexistence of other conditions that could potentially associate with thymic hyperplasia also supports the diagnosis of MG. PMID- 26363967 TI - Significant response to immune therapies in a case of subacute necrotizing myopathy and FKRP mutations. AB - Necrotizing myopathies can be encountered in various conditions as acquired myopathies (toxic or autoimmune) or muscular dystrophies. We report a twenty-year old Caucasian woman who presented with clinical findings suggestive of an inflammatory myopathy: subacute onset of lower limb muscle weakness, myalgia, weight loss and absence of family history. The serum creatine kinase level was elevated at 4738 IU/L (normal range, 25-175 IU/L). Muscle biopsy was consistent with necrotizing myopathy. The patient showed significant clinical improvement following corticosteroid, azathioprine and intravenous immunoglobulin treatments. Biological tests revealed no specific autoantibodies associated with necrotizing autoimmune myopathies. Immunohistochemical staining for sarcolemmal proteins in muscle biopsy samples finally led to a diagnosis of limb-girdle muscular dystrophy 2I (fukutin-related protein gene mutations). The response to immune therapies suggested a possible inflammatory component associated with the muscular dystrophy and highlighted the potential benefit of corticosteroid treatment in patients with LGMD2I and subacute onset. PMID- 26363968 TI - Attention-deficit/hyperactivity disorder, methylphenidate use and the risk of developing schizophrenia spectrum disorders: A nationwide population-based study in Taiwan. AB - This study estimated the risk of developing psychotic disorders by comparing children with ADHD to non-ADHD controls, and to examine whether methylphenidate (MPH) treatment influences the risks of psychotic disorders. A nationwide cohort of patients who were newly diagnosed with ADHD (n=73,049) and age- and gender matched controls (n=73,049) were selected from Taiwan's National Health Insurance database from January 2000 to December 2011. All participants were observed until December 31, 2011. Cox regression models were used to estimate the effects of ADHD diagnosis and MPH use on subsequent outcomes. Having a diagnosis of any psychotic disorder and of schizophrenia were set as two different outcomes and were analyzed separately. Compared to the control group, the ADHD group showed significantly increased risk of developing any psychotic disorder (adjusted hazard ratio [aHR], 5.20; 95% confidence interval [CI], 4.30-6.30) and schizophrenia (aHR, 4.65; 95% CI, 3.59-6.04). Compared to ADHD patients without psychosis, patients with ADHD who developed psychosis had significantly older age at first diagnosis of ADHD (9.4+/-3.3years vs. 10.6+/-4.0years). Among patients with ADHD, MPH use significantly increased the risk of developing any psychotic disorder (aHR, 1.20; 95% CI, 1.04-1.40), but did not increase the risk of developing schizophrenia (aHR, 1.16; 95% CI, 0.94-1.42). The results indicated that previous diagnoses of ADHD are a powerful indicator of developing psychotic disorders. Nevertheless, the specific mechanisms of the relationships between ADHD, MPH use and psychotic disorders need further elucidation in future clinical studies. PMID- 26363969 TI - Psychiatric disorders in child and adolescent offspring of patients with schizophrenia and bipolar disorder: A controlled study. AB - BACKGROUND: Early clinical manifestations predating schizophrenia (SZ) and bipolar disorder (BP) have not been fully characterized. Child offspring studies are a valuable opportunity to study the natural history of the illness from its earliest stages. However, there is limited evidence assessing young offspring of SZ and BP simultaneously. We set out to assess rates of psychiatric disorders in child and adolescent offspring of SZ and BP, relative to offspring of community controls, so as to characterize the early phenotype of the disorders comparatively. METHODS: SZ and BP parents with offspring aged 7-17years were recruited through adult mental health services of two tertiary hospitals. Community control (CC) parents were recruited from the same geographical area. Ninety BP-offspring, 41 SZ-offspring and 107 CC-offspring were assessed using the K-SADS-PL by child psychiatrists blinded to parental status. Differences in prevalence of psychiatric disorders between groups were adjusted for confounders and for sibling correlation using generalised estimating equations. RESULTS: We found a gradient of clinical severity and social disadvantage between SZ, BP and CC-offspring. After adjusting for socio-demographic confounders, SZ and BP offspring presented higher rates of attention deficit hyperactivity disorder (ADHD) than CC-offspring. ADHD was more prevalent in SZ-offspring than BP offspring, and BP-offspring presented a higher prevalence of depression than CC offspring. CONCLUSIONS: The higher rates of ADHD in SZ-offspring suggest that abnormal neurodevelopmental processes may exert a stronger influence in SZ than BP. Follow-up of these children will help elucidate the role of ADHD and depression phenotypes in predicting future transition to SZ or BP. PMID- 26363971 TI - Intra-arterial Therapy in the Early Treatment of Acute Ischaemic Stroke. PMID- 26363970 TI - Abnormal GABAergic function and face processing in schizophrenia: A pharmacologic fMRI study. AB - The involvement of the gamma-aminobutyric acid (GABA) system in schizophrenia is suggested by postmortem studies and the common use of GABA receptor-potentiating agents in treatment. In a recent study, we used a benzodiazepine challenge to demonstrate abnormal GABAergic function during processing of negative visual stimuli in schizophrenia. This study extended this investigation by mapping GABAergic mechanisms associated with face processing and social appraisal in schizophrenia using a benzodiazepine challenge. Fourteen stable, medicated schizophrenia/schizoaffective patients (SZ) and 13 healthy controls (HC) underwent functional MRI using the blood oxygenation level-dependent (BOLD) technique while they performed the Socio-emotional Preference Task (SePT) on emotional face stimuli ("Do you like this face?"). Participants received single blinded intravenous saline and lorazepam (LRZ) in two separate sessions separated by 1-3weeks. Both SZ and HC recruited medial prefrontal cortex/anterior cingulate during the SePT, relative to gender identification. A significant drug by group interaction was observed in the medial occipital cortex, such that SZ showed increased BOLD signal to LRZ challenge, while HC showed an expected decrease of signal; the interaction did not vary by task. The altered BOLD response to LRZ challenge in SZ was significantly correlated with increased negative affect across multiple measures. The altered response to LRZ challenge suggests that abnormal face processing and negative affect in SZ are associated with altered GABAergic function in the visual cortex, underscoring the role of impaired visual processing in socio-emotional deficits in schizophrenia. PMID- 26363972 TI - An Experimental Evaluation of Device/Arterial Wall Compliance Mismatch for Four Stent-Graft Devices and a Multi-layer Flow Modulator Device for the Treatment of Abdominal Aortic Aneurysms. AB - OBJECTIVE/BACKGROUND: To investigate experimentally the arterial wall/device compliance mismatch of four stent-graft devices and a multilayer flow modulator within the supra- and infrarenal locations for the treatment of abdominal aortic aneurysms (AAA). METHODS: Five devices (MFM, EndurantII, Excluder, Zenith, and Fortron) were tested under physiological flow conditions within a flow simulator system comprising of a patient-specific thin-walled flexible AAA perfusion model with replicated intraluminal thrombus, supported by the spinal column. Devices were submitted to circumferential force tests and implanted in the perfusion model for circumferential arterial pressure/diameter measurements. Parameters, including radial resistive force, supra-/infrarenal compliance, pulsatile arterial energy loss (PAEL), pulse wave velocity (PWV), and wave reflection coefficient (Gamma), were computed to characterise the devices' performance. RESULTS: The Zenith and EndurantII devices had the highest radial resistive force (up to 3 N/cm), while the Fortron device had the lowest (0.11 N/cm). Supra- and infrarenal compliance varied between 6.9-5.1 * 10(-4)/mmHg and 4.8-5.4 * 10( 4)/mmHg, respectively. Two devices (EndurantII and Excluder) significantly decreased infrarenal compliance by 13-26% (p < .001). Four devices increased the PAEL by 13-44% (p < .006). The PWV ranged from 10.9 m/s (MFM; p = .164) to 15.1 m/s (EndurantII; p < .001). There was an increase of 8-238% (p < .001) in the reflection coefficient for all devices. CONCLUSION: Commercially available endovascular devices lower the aortic wall compliance after implantation. The MFM was found to be the most compliant in the suprarenal region, while the Fortron device was the most compliant in the infrarenal region. Choosing the most compliant devices for treating AAAs produces positive gains in the aortic elastic recoil, thus minimising the device related complications. PMID- 26363973 TI - Protective effects of protostemonine on LPS/GalN-induced acute liver failure: Roles of increased hepatic expression of heme oxygenase-1. AB - Here, we explored protective effects of protostemonine (PSN), on mouse acute liver failure induced by lipopolysaccharide/d-galactosamine (LPS/GalN). PSN dose dependently declined LPS/GalN-induced lethality of mice as well as increase of ALT/AST activities in their serum. Hepatoprotective effects of PSN were also supported by liver histopathological examinations. After LPS/GalN treatment, severe oxidative stresses in the liver could be detected by boosted MDA and ROS as well as decreased GSH. Moreover, hepatic expression of pro-inflammatory cytokines, including TNF-alpha, IL-1beta and IL-6, were sharply elevated. These symptoms were dose-dependently ameliorated by PSN. Mechanistically, PSN promoted the transcription and translation of heme oxygenase-1 (HO-1) in hepatocytes and liver Kupffer cells. Nrf2 is a master transcription factor contributing to the expression of HO-1. PSN elevated Nrf2 nuclear accumulation and enhanced Nrf2/HO-1 promoter interaction. Suppressing enzyme activity of HO-1 by co-treating mice with HO-1 inhibitor ZnPP abolished protective effects of PSN. ZnPP also abrogated alleviative impacts of PSN on LPS/GalN-mediated hepatic oxidative stresses and inflammatory responses. Finally, we showed that PSN exhibited undetectable toxic effects on vital organs of mice. Our findings suggested that PSN is able to attenuate LPS/GalN-induced acute liver failure and upregulating HO-1 expression is implicated in its hepatoprotective activity. PMID- 26363974 TI - Epigallocatechin-3-gallate attenuates bone cancer pain involving decreasing spinal Tumor Necrosis Factor-alpha expression in a mouse model. AB - Tumor metastasis to bone often elicits a wide array of symptoms, in which pain is a significant factor in catastrophic complications of bone cancer. The complete understanding of bone cancer-related pain is still unknown, while several pathophysiological components have been suggested, from tumor-stimulated osteolysis, nerve compression, stimulations of ion channels, and locally generated inflammatory cytokines. In particular, it has been shown that pro inflammatory cytokine TNFalpha-mediated actions are necessary for the development of bone cancer pain. As a member of catechin family in green tea extracts, EGCG (Epigallocatechin-3-gallate) can reduce excess free radicals and attenuate overactive inflammatory signaling including TNFalpha. In addition, EGCG or its related molecules have been used to control neuropathic pain in various preclinical settings. However, its potential use in bone cancer-caused pain has not yet been reported. Here we show that treating a mouse model of bone cancer by EGCG, results in a dramatic reduction in pain behavior and a significant decrease of TNFalpha expression within the spinal cord of tumor-bearing mice. Thus, this study reveals an anti-nociceptive role for EGCG in the progression of pain caused by tumor bone metastasis, and highlights a potential scheme by using anti TNFalpha as a therapeutic option for osteolytic pain. PMID- 26363975 TI - Nicotine promotes rooting in leaf explants of in vitro raised seedlings of tomato, Lycopersicon esculentum Miller var. Pusa Ruby. AB - Nicotine promotes rooting in leaf explants of tomato (Lycopersicon esculentum Miller var. Pusa Ruby). Nicotine at 10(-9) to 10(-3) M concentrations was added to the MS basal medium. The optimum response (three-fold increase in rooting) was obtained at 10(-7) M nicotine-enriched MS medium. At the same level i.e. 10(-7) M Nicotine induced dramatic increase (11-fold) in the number of secondary roots per root. We have shown earlier that exogenous acetylcholine induces a similar response in tomato leaves. Since nicotine is an agonist of one of the two acetylcholine receptors in animals, its ability to simulate ACh action in a plant system suggests the presence of the same molecular mechanism operative in both, animal and plant cells. PMID- 26363976 TI - Norisoboldine ameliorates DSS-induced ulcerative colitis in mice through induction of regulatory T cells in colons. AB - Norisoboldine (NOR), the main active constituent of Radix Linderae, was previously demonstrated to ameliorate collagen-induced arthritis in rats through regulating the imbalance of T cells in intestines, which implied its therapeutic potential in inflammatory bowel disease. Here, we investigated the effect of NOR on ulcerative colitis (UC) induced by dextran sulfate sodium (DSS) in mice. Results showed that NOR (20, 40mg/kg) markedly reduced the symptoms of colitis, the levels of IL-1beta and TNF-alpha, and the activation of ERK, p38 MAPK and NF kappaB-p65. NOR only slightly decreased the levels of IFN-gamma and IL-17A in mouse colons, but it dramatically increased the level of IL-10 at both protein and mRNA grades. Consistently, NOR increased the number of CD4(+)CD25(+)Foxp3(+) Treg cells more obviously than it decreased that of CD4(+)IL-17(+) Th17 cells in mesenteric lymph nodes (MLNs) and colonic lamina proprias (LPs) of colitis mice, and promoted the expression of Foxp3 mRNA in colon tissues. It could facilitate the in vitro differentiation of Treg cells from naive T cells and promote the phosphorylations of Smad2/3 in colon tissues of colitis mice. On the other hand, NOR did not affect the expressions of homing receptors CCR9 and alpha4beta7 in SPs, and homing ligands CCL25 and Madcam-1 in MLNs and colonic LPs, suggesting that the increase of Treg cells in colons by NOR was not due to gut homing. In conclusion, NOR can ameliorate DSS-induced UC in mice, and the mechanisms involve reduction of pro-inflammatory cytokines and selective induction of Treg cells in colons. PMID- 26363977 TI - A correction in the CDM methodological tool for estimating methane emissions from solid waste disposal sites. AB - Solid waste disposal sites (SWDS) - especially landfills - are a significant source of methane, a greenhouse gas. Although having the potential to be captured and used as a fuel, most of the methane formed in SWDS is emitted to the atmosphere, mainly in developing countries. Methane emissions have to be estimated in national inventories. To help this task the Intergovernmental Panel on Climate Change (IPCC) has published three sets of guidelines. In addition, the Kyoto Protocol established the Clean Development Mechanism (CDM) to assist the developed countries to offset their own greenhouse gas emissions by assisting other countries to achieve sustainable development while reducing emissions. Based on methodologies provided by the IPCC regarding SWDS, the CDM Executive Board has issued a tool to be used by project developers for estimating baseline methane emissions in their project activities - on burning biogas from landfills or on preventing biomass to be landfilled and so avoiding methane emissions. Some inconsistencies in the first two IPCC guidelines have already been pointed out in an Annex of IPCC latest edition, although with hidden details. The CDM tool uses a model for methane estimation that takes on board parameters, factors and assumptions provided in the latest IPCC guidelines, while using in its core equation the one of the second IPCC edition with its shortcoming as well as allowing a misunderstanding of the time variable. Consequences of wrong ex-ante estimation of baseline emissions regarding CDM project activities can be of economical or environmental type. Example of the first type is the overestimation of 18% in an actual project on biogas from landfill in Brazil that harms its developers; of the second type, the overestimation of 35% in a project preventing municipal solid waste from being landfilled in China, which harms the environment, not for the project per se but for the undue generated carbon credits. In a simulated landfill - the same amount of waste for 20 years -, the error would be an overestimation of 25% if the CDM project activity starts from the very first year or an underestimation of 15% if it starts just after the landfill closure. Therefore, a correction in the tool to calculate emissions from landfills as adopted by the CDM Executive Board is needed. Moreover, in countries not using the latest IPCC guidelines, which provides clear formulas to prevent misunderstandings, inventory compilers can also benefit from this paper by having more accurate results in national GHG inventories related to solid waste disposal, especially when increasing amounts of waste are landfilled, which is the case of the developing countries. PMID- 26363978 TI - Structure-oriented beliefs and disability due to back pain. AB - The modern costly epidemic of disability due to back pain is considered to be effectively the result of various beliefs as to the cause, and therefore appropriate management, of this commonplace, generally benign and self-limiting symptom. Prominent is the belief that spontaneous or provoked pain is evidence of some problem with the structure of the spine. As such, along with therapeutic rest, the logical means of relieving pain would be with interventions which actually or purportedly influence structure. Evidence is discussed endorsing the existence, likely origins, potency, fallacy and dysfunctional consequences of this view in the context of the unique 20th Century phenomenon, chronic disability following non-specific back pain. PMID- 26363979 TI - The effect of lung compliance and experience on manual hyperinflation. AB - This study was designed to investigate the factors which affect the safe and effective performance of manual hyperinflation by physiotherapists. To determine this, experienced and student physiotherapists were requested to deliver manual hyperinflations at tidal volumes of 1000mLorpeak inspiratory pressures of 15cm H2O during a series of trials with variations in lung compliance. These hyperinflations were delivered into an artificial lung system. Subjects were blind to random changes in lung compliance and were only allowed the feel of the bag for feedback during testing. It was found that compliance had a significant effect on the tidal volumes and pressures generated, and bothgroups of subjects allowed peak inspiratory pressure to rise significantly when lung compliance was low. Experience, hand size and grip strength of individuals did not influence these results. PMID- 26363980 TI - New Zealand patients' understanding of brand substitution and opinions on copayment options for choice of medicine brand. AB - Objective The aim of the present study was to better understand the views and experiences of New Zealand patients on switching between brands of prescription medicines and on alternative funding options for the provision of medicines, including an increase in copayments. Methods A self-administered questionnaire was offered to selected patients through participating community pharmacies. Pharmacies were stratified according to level of deprivation of the community served before random selection and invitation for involvement in the study. Patient understanding of and rationale for brand substitution was assessed. Preference for different copayment options was elicited, together with demographic and other explanatory information. Results In all, 194 patient completed questionnaires were returned. Some gaps in patient knowledge and understanding of brand changes were evident. Most respondents indicated a preference for the existing subsidy arrangements with little desire expressed for alternatives. Around half were willing to contribute towards paying for a choice of brand other than the subsidised brand; however, the maximum contribution nominated was disproportionately lower than real cost differences between originator brand and generics. Conclusion The findings of the present study suggest that although most patients have experienced brand changes without any problems occurring, a lack of knowledge about substitution does persist. There may be some additional gain in ensuring New Zealanders are aware of the full cost of their medicines at the point of dispensing to reinforce the benefits of the Pharmaceutical Management Agency (PHARMAC) purchasing model. What is known about the topic? Generic reference pricing is used as a mechanism to make savings to pharmaceutical budgets; however, reticence to the use of generic medicines persists. What does this paper add? Most New Zealand patients experience brand changes without any problems occurring; however, a lack of knowledge about substitution does persist. The dollar value patients indicate they would contribute for brand choice is lower than the true cost difference between brands. What are the implications for practitioners? Opportunities exist for healthcare professionals to reinforce generic policies and there may be some additional gain in ensuring New Zealanders are aware of the full cost of their medicines at the point of dispensing. PMID- 26363981 TI - Long-term durability of alumina ceramic heads in THA. AB - BACKGROUND: The optimal type of bearing for hip arthroplasty remains a matter of debate. Ceramic-on-polyethylene (CoP) bearings are frequently used in younger and more active patients to reduce wear and increase biocompatibility compared to Metal-on-Polyethylene (MoP) bearings. However, in comparison to metal heads, the fracture risk of ceramic heads is higher. In addition, ceramic head fractures pose a serious complication which often necessitates major revision surgery. To date, there are no long-term data (>20 years of follow-up) reporting fracture rates of the ceramic femoral heads in CoP bearings. The purpose of this research was to investigate long-term CoP fracture rate. METHODS: We evaluated the clinical and radiographic results of 348 cementless THAs treated with 2nd generation Biolox Al2O3 Ceramic-on-Polyethylene (CoP) bearings consecutively implanted between January 1985 and December 1989. The mean age at implantation was 57 years. The patients were followed for a minimum of 20 years. At the final 111 had died, and 5 were lost to follow-up. The cumulative incidence of ceramic head fractures in the long-term was estimated using a competing risk analysis. RESULTS: The cumulative incidence of ceramic head fracture after 22-years was estimated with a competing risk analysis at 0.29% after 22-years (SE = 2.09%; 95% - CI: 0.03-1.5%). The radiographic analysis revealed no impending failures at final follow-up. DISCUSSION/CONCLUSION: The fracture rate of second-generation ceramic heads using a CoP articulation remains very low into the third decade after cementless THA. PMID- 26363982 TI - Patterns of Venous Thromboembolism Prophylaxis During Treatment of Acute Leukemia: Results of a North American Web-Based Survey. AB - BACKGROUND: Venous thromboembolism (VTE) occurs in 2% to 12% of patients with acute leukemia (AL) despite disease- and therapy-associated thrombocytopenia, and it can be associated with significant morbidity and mortality. Because of the few high-quality studies, there are no evidence-based guidelines for VTE prophylaxis in this patient population. We sought to determine the spectrum of practice regarding prevention of VTE in patients with AL during induction and consolidation therapies. METHODS: We conducted a 19-question Web-based survey directed at North American providers caring for these patients. One hundred fifty one of 215 responses received were eligible for analysis, with a response rate of 20.9% among physicians who treated leukemias. RESULTS: Overall, 47% and 45% of providers reported using pharmacologic VTE prophylaxis during induction and consolidation phases, respectively. Approximately 15% of providers did not provide any VTE prophylaxis, while 36% used mechanical methods and ambulation. Among providers who did not recommend pharmacologic prophylaxis, the most commonly cited reasons were the perceived high risk of bleeding (51%), absence of data supporting use (38%), and perceived low risk of VTE (11%). CONCLUSION: Large, prospective studies are needed to define the safest and most effective approach to VTE prevention in patients with AL. PMID- 26363983 TI - Direct and indirect toxic effects of cotton-derived cellulose nanofibres on filamentous green algae. AB - Recently, cellulose nanofibers (CNFs) have attracted considerable attention as natural, abundant polymers with excellent mechanical properties and biodegradability. CNFs provide a new materials platform for the sustainable production of high-performance nano-enable products for various applications. Given the increasing rates of CNF production, the potential for their release to the environment and the subsequent impact on ecosystem is becoming an increasing concern that needs to be addressed. Here, we used the Klebsormidium flaccidum as a bioindicator organism of terrestrial and freshwater habitats pollution using a battery of biomarkers. Our results show that cotton CNFs inhibit the proliferation of algae and induce morphological changes in them. The two main toxicity mechanisms induced by cotton CNFs are: (i) a direct contact of CNFs with the cell wall and cellular membrane and (ii) an indirect effect through the generation of reactive oxygen species (ROS). PMID- 26363984 TI - Environmental distribution and associated human health risk due to trace elements and organic compounds in soil in Jiangxi province, China. AB - The government of China launched its first national soil quality and pollution survey (NSQPS) during April 2006 to December 2013. Data gathered in several earlier soil surveys were rarely used to understand the status of pollution. In this study, the dataset collected at the provincial level was analyzed for the first time. Concentrations, distribution, diversity, and human health risks of trace elements (As, Cd, Co, Cr, Cu, Hg, Mn, Ni, Pb, Se, V and Zn) and organic pollutants (benzene hexachloride (BHCs), dichlorodiphenyltrichloroethanes (DDTs), phthalic acid esters (PAEs), polycyclic aromatic hydrocarbon (PAHs), polychlorinated biphenyls (PCBs), and petroleum hydrocarbons (PHCs)) in surface soil samples collected across Jiangxi province,China were presented. The results showed that, the proportion of contaminants with concentrations higher than their corresponding regulatory reference value ranged from 0.12% to 17%. It is worth note that, the local residents are exposed to moderate non-carcinogenic and carcinogenic risks at some sites. The comprehensive analysis of soil pollutants provide baseline information for establishing a long-term soil environmental monitoring program in Jiangxi province, China. PMID- 26363986 TI - Removing the primary tumour in metastatic breast cancer. PMID- 26363985 TI - Locoregional treatment versus no treatment of the primary tumour in metastatic breast cancer: an open-label randomised controlled trial. AB - BACKGROUND: The role of locoregional treatment in women with metastatic breast cancer at first presentation is unclear. Preclinical evidence suggests that such treatment might help the growth of metastatic disease, whereas many retrospective analyses in clinical cohorts have suggested a favourable effect of locoregional treatment in these patients. We aimed to compare the effect of locoregional treatment with no treatment on outcome in women with metastatic breast cancer at initial presentation. METHODS: In this open-label, randomised controlled trial, we recruited previously untreated patients (<=65 years of age with an estimated remaining life expectancy of at least 1 year) presenting with de-novo metastatic breast cancer from Tata Memorial Centre, Mumbai, India. Patients were randomly assigned (1:1) to receive locoregional treatment directed at their primary breast tumour and axillary lymph nodes, or no locoregional treatment, by a computer generated block randomisation sequence (block size of four). Randomisation was stratified by site of distant metastases, number of metastatic lesions, and hormone receptor status. Patients with resectable primary tumour in the breast that could be treated with endocrine therapy were randomly assigned upfront, whereas those with an unresectable primary tumour were planned for chemotherapy before randomisation. Of the patients who had chemotherapy before randomisation, we randomly assigned patients who had an objective tumour response after six to eight cycles of chemotherapy. The primary endpoint was overall survival analysed by intention to treat. This study is registered with ClinicalTrials.gov, NCT00193778. FINDINGS: Between Feb 7, 2005, and Jan 18, 2013, of the 716 women presenting with de-novo metastatic breast cancer, we randomly assigned 350 patients: 173 to locoregional treatment and 177 to no locoregional treatment. At data cut-off of Nov 1, 2013, median follow-up was 23 months (IQR 12.2-38.7) with 235 deaths (locoregional treatment n=118, no locoregional treatment n=117). Median overall survival was 19.2 months (95% CI 15.98-22.46) in the locoregional treatment group and 20.5 months (16.96-23.98) in the no-locoregional treatment group (HR 1.04, 95% CI 0.81-1.34; p=0.79), and the corresponding 2-year overall survival was 41.9% (95% CI 33.9-49.7) in the locoregional treatment group and 43.0% (35.2-50.8) in the no locoregional treatment group. The only adverse event noted was wound infection related to surgery in one patient in the locoregional treatment group. INTERPRETATION: There is no evidence to suggest that locoregional treatment of the primary tumour affects overall survival in patients with metastatic breast cancer at initial presentation who have responded to front line chemotherapy, and this procedure should not be part of routine practice. PMID- 26363987 TI - Impact of aflatoxin B1 on the pharmacokinetic disposition of enrofloxacin in broiler chickens. AB - The potential impact of subchronic exposure of aflatoxin B1 was investigated on the pharmacokinetic disposition of enrofloxacin in broiler chickens. Broiler chickens given either normal or aflatoxin B1 (750MUg/kg diet) supplemented diet for 6 weeks received a single oral dose of enrofloxacin (10mg/kg body wt). Blood samples were drawn from the brachial vein at predetermined time intervals after drug administration. Enrofloxacin plasma concentrations analyzed by RP-HPLC were significantly lower in aflatoxin B1-exposed broiler chickens at 0.167, 0.5 and 1.0h after drug administration. In aflatoxin B1-exposed broiler chickens, the absorption rate constant (ka) of enrofloxacin (0.20+/-0.05h(-1)) was significantly decreased as compared to the unexposed birds (0.98+/-0.31h(-1)). The values of [Formula: see text] , tmax and AUC0-infinity of enrofloxacin were nonsignificantly increased by 17%, 26% and 17% in aflatoxin-exposed broiler chickens, respectively. Subchronic aflatoxin B1 exposure markedly decreased the initial absorption of enrofloxacin without significantly influencing other pharmacokinetic parameters in broiler chickens. PMID- 26363988 TI - Alpha-ketoglutarate attenuates toxic effects of sodium nitroprusside and hydrogen peroxide in Drosophila melanogaster. AB - The protective effects of dietary alpha-ketoglutarate (AKG) are described that aid fruit flies, Drosophila melanogaster, to resist sodium nitroprusside (SNP) and hydrogen peroxide toxicity. Food supplementation with 10mM AKG alleviated toxic effects of 1mM SNP added to food and improved fly development. Dietary AKG also prevented the increase in levels of oxidative stress markers seen in SNP reared adult flies. In vitro AKG did not affect the rate of SNP decomposition and did not bind iron and nitrite ions released in this process. Alpha-ketoglutarate also displayed high H2O2-scavenging activity in vitro and efficiently protected adult flies against this compound in combined treatments. Based on the observed antioxidant activity of AKG, it may be suggested that the antioxidant mode of AKG action (apart from its cyanide-binding capability) may be used to prevent the toxic effects of SNP and improve general physiological state of D. melanogaster and other animals and humans. PMID- 26363989 TI - [Who is the user of socio-health interventions and what are their needs?]. AB - Socio-health interventions include performance and care intended to attend to the needs of people who have suffered a decrease in their personal autonomy because of their age, illness or disability. Oriented towards achieving an improvement in the quality of life of people in that situation, they try to meet the requirements of people in an integrated way. To intervene in those situations involves providing technical aids and environmental, custom and social changes as well as personal care needed to improve their quality of life and enhance their skills and well-being. Scientific advances and demographic and social changes have determined a change in the profile of socio-health interventions' receivers, highlighting longevity, chronicity of processes and aging of the informal caregiver. The aim of this work is to characterize the person receiving the social-health interventions and to reflect on what their needs are. To do this we have conducted a biomedical studies' review through literature searches at ScienceDirect as well as a review of national institutional documentation related to people in dependent situations and their family caregivers. People who need socio-health help establish a heterogeneous population in respect of their needs. Both the person with disabilities and their informal caregiver need to be considered as an object of interest and attention. PMID- 26363990 TI - [Is a strategy of bio-socio-ethic necessary?]. AB - AIM: The aim of this paper is to assess the need for a common ethics strategy shared by 2 of the cornerstones of human welfare: the healthcare and social services sectors. METHOD: An observational cross-sectional descriptive study was performed by surveying social services and healthcare professionals. A purposive sampling technique was used. The questionnaire consisted of 10 questions about ethical conflicts in professional practice and respondents' views on a proposed shared approach to bioethics and ethics in social intervention. RESULTS: 124 professionals completed the questionnaire, 56% of the health sector and 44% of the social services sector. About 90% professionals surveyed had had to make difficult ethical decisions in their work and would welcome a common approach to ethics in the social services and healthcare sectors. 75% said that conflicts are occurring more frequently in both sectors simultaneously and that they were resolved preferably individually and independently. CONCLUSIONS: The survey respondents believe that a common approach to tackling ethical conflicts in professional practice is required. Nevertheless, it is still rare for ethics committees to intervene in the conflict resolution process and for decision making support and evaluation tools to be used. PMID- 26363991 TI - [Complex chronic care situations and socio-health coordination]. AB - Patient-centered healthcare is currently one of the most pursued goals in health services. It is necessary to ensure a sufficient level of cooperative and coordinated work between different providers and settings, including family and social and community resources. Clinical integration occurs when the care provided by health professionals and providers is integrated into a single coherent process through different professions using shared guidelines and protocols. Such coordination can be developed at three levels: macro, which involves the integration of one or more of the three basic elements that support health care (the health plan, primary care and specialty care), with the aim of reducing fragmentation of care; meso, where health and social services are coordinated to provide comprehensive care to elderly and chronic patients; and micro, aimed to improve coordination in individual patients and caregivers. The implementation of new roles, such as Advanced Practice Nursing, along with improvements in family physicians' problem-solving capacity in certain processes, or modifying the place of provision of certain services are key to ensure services adapted to the requirements of chronic patients. PMID- 26363992 TI - [Predictors of institutionalization of elderly persons in dependency situation in Andalusia]. AB - OBJECTIVE: Identifying preferences regarding type of care and risk factors for institutionalization of elderly persons in dependency situations in Andalusia. METHODS: The data on 200,039 persons registered in the System for Autonomy and Dependency Care over the period 2007-2012 were analysed. The study population was described in terms of: age, dependency situation, preferences, support network and clinical factors at the time of inclusion in the study. Separate analysis was made for men and women. A logistic regression model was designed to determine the risk factors for institutionalization for each sex. RESULTS: 87,4% of women and 85,9% of men expressed their wish to receive care in their own home. The risk of institutionalization is three times higher among men than among women. Among women, the risks of institutionalization are: level of dependency, wishing to move into a residential care home, medium consistency and fragility of support network and being diagnosed with dementia. Among men, the risks are: wishing to move into a residential care home and low or medium consistency of support network. CONCLUSIONS: Care in the home is the preferred alternative for elderly persons in dependency situations. The risk of institutionalization is conditioned more by the preferences of the person and their family and the characteristics of the support network than by individual's clinical condition. PMID- 26363993 TI - [Experiences, models and key factors for the coordination and integration of social and health services]. PMID- 26363994 TI - Sphingomonas fonticola sp. nov., isolated from spring water. AB - A bacterial strain designated TNR-2T was isolated from spring water in Taiwan and characterized using a polyphasic taxonomic approach. Cells of strain TNR-2T were aerobic,Gram-stain-negative, straight rods, motile by a single polar flagellum and containing poly-beta-hydroxybutyrate. The cells were covered by large capsules and formed yellow colonies.Growth occurred at 15-37 degrees C (optimum, 20-30 degrees C), with 0-1.0% NaCl (optimum, 0-0.1 %)and at pH 5.0-8.0 (optimum, pH 6.0). According to a phylogenetic tree based on 16S rRNA gene sequence analysis, strain TNR-2T belonged to the genus Sphingomonas and clustered with Sphingomonas alpina S8-3T, with which it shared the highest 16S rRNA gene sequence similarity (95.6 %). The major fatty acids (.10 %) of strain TNR-2T were C18 : 1omega7c, C17 : 1omega6c and C16 : 0. The DNA G+C content was 62.8 mol%. The major isoprenoid quinone was Q-10.The major polyamine was homospermidine. The polar lipid profile consisted ofsphingoglycolipid, phosphatidylethanolamine, phosphatidylglycerol,phosphatidylmonomethylethanolamine, phosphatidylcholine, diphosphatidylglycerol,two uncharacterized glycolipids and an uncharacterized phospholipid. Phenotypic characteristics of the novel strain differed from those of the closest related species of the genus Sphingomonas. On the basis of the genotypic, chemotaxonomic and phenotypic data, strain TNR-2T represents a novel species in the genus Sphingomonas, for which the nameS phingomonas fonticola sp. nov. is proposed. The type strain is TNR-2T (=BCRC80539T=LMG 27384T=KCTC 32258T). PMID- 26363995 TI - Expanding diversity of glycan receptor usage by rotaviruses. AB - Rotaviruses are major etiologic agents of severe gastroenteritis in human and animals, infecting the mature intestinal epithelium. Their attachment to host cell glycans is mediated through the virion spike protein. This is considered to be crucial for successful host cell invasion by rotaviruses. Recent studies have greatly expanded our understanding of the diversity of glycans commonly recognized by rotaviruses, to include the ganglioside GM1a and histo-blood group antigens. Here, these new findings are integrated with advances in knowledge of spike protein structure, rotavirus entry mechanisms and innate intestinal immunity to provide an overview of the variety of rotavirus glycan receptors and their roles in cell penetration, host tropism and pathogenesis. PMID- 26363997 TI - [Type I interferonopathies]. AB - Type I interferonopathies are a group of Mendelian disorders characterized by a common physiopathology: the up-regulation of type I interferons. To date, interferonopathies include Aicardi-Goutieres syndrome, familial chilblain lupus, spondyenchondromatosis, PRoteasome-associated auto-inflammatory syndrome (PRAAS) and Singleton-Merten syndrome. These diseases present phenotypic overlap including cutaneous features like chilblain lupus, that can be inaugural or present within the first months of life. This novel set of inborn errors of immunity is evolving rapidly, with recognition of new diseases and genes. Recent and improved understanding of the physiopathology of overexpression of type I interferons has allowed the development of targeted therapies, currently being evaluated, like Janus-kinases or reverse transcriptase inhibitors. PMID- 26363998 TI - [Infantile scurvy: Two cases]. AB - BACKGROUND: Scurvy is the classic and most severe form of vitamin C deficiency. This condition has become extremely rare among children in the industrialized countries. PATIENTS AND METHODS: We report the case of two boys presenting bone pain associated with haemorrhagic gingivitis, with perifollicular purpura of the lower limbs in one boy. The children had an unbalanced diet. Scurvy was associated with vitamin D and iron deficiency. The dermatological and radiological abnormalities seen were characteristic and a favourable outcome was rapidly obtained following supplementation. DISCUSSION: The possibility of this forgotten historical illness should not be overlooked in the presence of these dermatological and rheumatologic signs, since this can help avoid unnecessary or excessively aggressive investigations. PMID- 26363996 TI - The microbiome modulates arbovirus transmission in mosquitoes. AB - Mosquito-transmitted arthropod-borne viruses (arboviruses) such as dengue virus, chikungunya virus, and West Nile virus constitute a major public health burden and are increasing in severity and frequency worldwide. The microbiota associated with mosquitoes (comprised of viruses, bacteria, fungi and protozoa) can profoundly influence many host phenotypes including vector competence, which can either be enhanced or suppressed. Thus, the tripartite interactions between the mosquito vector, its microbiota and the pathogens they transmit offer novel possibilities to control arthropod-borne diseases. PMID- 26363999 TI - [Angiomatoid fibrous histiocytoma in children: 6 cases]. AB - BACKGROUND: Angiomatoid fibrous histiocytoma (AFH) is a soft-tissue tumour of uncertain differentiation most often arising in the extremities of children and young adults. AFH is a little-known neoplasm and its rarity may result in it being misdiagnosed as either a reactive lesion or a benign or higher-grade tumour. We report 6 cases of AFH in children and we review the clinicopathological and molecular features of this neoplasm published in the literature. PATIENTS AND METHODS: The children (aged 4 to 16 years) presented a single nodule involving the forearm (4/6), the trunk or the buttock, and all 5 nodules appeared spontaneously. Microscopic examination revealed well circumscribed nodular lesions comprising a fibrous pseudo-capsule, haemorrhagic non-endothelial-lined pseudocystic spaces, and sheets of spindle and ovoid cells with dense surrounding lymphoplasmacytic infiltrate. Tumours were positive for desmin, CD68, CD99 and smooth-muscle actin markers. A fusion gene (EWSR1-ATF1) was found in the 3 cases in which molecular investigation was performed. DISCUSSION: In our series, a diagnosis of AFH had in no event been evoked after clinical examination and radiological investigation. The diagnosis was based in all cases on recognition of characteristic features during histological examination and it was confirmed in 3 cases by the recognition of fusion genes. Complete excision with wide margins allowed complete cure in all cases, supporting a good prognosis of AFH, although long-term follow-up is still mandatory to rule out relapse or metastases, which although rare, are responsible for fatal cases. To avoid unnecessary surgery in patients with AFH, an ultrasound core-needle biopsy should be performed as a first step in order to provide precise diagnosis enabling complete excision to be performed, with the margins being decided in multidisciplinary meetings involving teams specialised in soft tissue tumours. PMID- 26364000 TI - [Risk factors associated with leg erysipelas (cellulitis) in sub-Saharan Africa: A multicentre case-control study]. AB - BACKGROUND: Acute bacterial cellulitis of the leg (erysipelas) is a common problem involving considerable morbidity in dermatology practice in Africa. Previous studies conducted in Europe and North Africa have highlighted lymphoedema and toe-web intertrigo as independent factors associated with leg erysipelas. The aim of this case-control study was to identify risk factors associated with leg erysipelas in sub-Saharan Africa, within a different socio economic and culture context. PATIENTS AND METHODS: We conducted a prospective case-control study in hospital dermatology departments in 8 sub-Saharan African countries over a 12-month period (October 2013 to September 2014). Each case of acute leg cellulitis was matched with 2 controls for age (+/-5 years) and sex. We analysed the general and local factors. RESULTS: During the study period, 364 cases (223 female, 141 male) were matched with 728 controls. The mean age was 42.15+/-15.15 years for patients and 42.11+/-36 years for controls. Multivariate analysis showed the following to be independent risk factors associated with leg erysipelas in our study: obesity (odds ratio [OR]=2.82 ; 95% confidence interval: 2.11-3.76), lymphoedema (OR=3.87, 95%CI: 2.17-6.89), voluntary cosmetic depigmentation (OR=4.29, 95%CI: 2.35-7.83), neglected traumatic wound (OR=37.2, 95%CI: 24.9-57.72) and toe-web intertrigo (OR=37.86, 95%CI: 22.27-64.5). CONCLUSION: The results of this study confirms the major role of local risk factors (toe-web intertrigo, lymphoedema) previously identified in other geographical settings. However, the originality of our study consists of the identification of voluntary cosmetic depigmentation as a risk factor for leg erysipelas in sub-Saharan Africa. PMID- 26364002 TI - Treatment Outcome of Repaired Root Perforation: A Systematic Review and Meta analysis. AB - INTRODUCTION: This study aimed to review systematically the reported treatment outcome of repaired root perforation and to identify any preoperative factors that may influence the outcome of such repair. METHODS: A comprehensive search was conducted by using 4 electronic databases, as well as manual search of cited references, to identify reports related to root perforation. Clinical studies published from 1950 to mid-2014 that evaluated the outcome of repaired root perforations were identified. Studies were further screened for similar characteristics for pooling of data for meta-analysis. RESULTS: Seventeen studies were included for systematic review and 12 suitable for meta-analysis. An overall pooled success rate of 72.5% (confidence interval, 61.9%-81.0%) was estimated for nonsurgical repair of root perforations. The use of mineral trioxide aggregate appeared to enhance the success rate to 80.9% (confidence interval, 67.1%-89.8%), but the difference was not statistically significant. The presence of pre existing radiolucency adjacent to the perforation site fared a lower chance of success after repair (P < .05). Maxillary teeth demonstrated a significantly higher success rate compared with their mandibular counterpart (P < .05). CONCLUSIONS: Within the limitations of this study, it may be concluded that nonsurgical repair of root perforation results in a success rate of more than 70%. Teeth in the maxillary arch and absence of preoperative radiolucency adjacent to the perforation are favorable preoperative factors for healing after perforation repair. In view of the relatively high rate of clinical success, nonsurgical repair may be considered as the preferred treatment to handle this complication that arises during root canal therapy. PMID- 26364001 TI - The changing epidemiology of Acinetobacter spp. producing OXA carbapenemases causing bloodstream infections in Brazil: a BrasNet report. AB - We evaluated the epidemiology of Acinetobacter spp. recovered from patients diagnosed with bloodstream infections in 9 tertiary hospitals located in all Brazilian geographic regions between April and August 2014. Although OXA-23 producing Acinetobacter baumannii clones were disseminated in most hospitals, it was observed for the first time the spread of OXA-72 among clonally related A. baumannii isolated from distinct hospitals. Interestingly, Acinetobacter pittii was the most frequent species found in a Northern region hospital. Contrasting with the multisusceptible profile displayed by A. pittii isolates, the tetracyclines and polymyxins were the only antimicrobials active against all A. baumannii isolates. PMID- 26364003 TI - Comparative Evaluation of the Efficiency of Manual and Rotary Gutta-percha Removal Techniques. AB - INTRODUCTION: This study aimed to evaluate the efficiency of 2 manual and 2 rotary gutta-percha (GP) removal techniques in terms of both the total operating time and GP remnants left in the canal. METHODS: GP was removed with manual techniques using H-files and xylene (H + X) and H-files and System B (H + SB) (SybronEndo, Orange, CA) and with rotary techniques using the ProTaper Univeral Retreatment (PTUR) (Dentsply Maillefer, Ballaigues, Switzerland) and D-RaCe Retreatment (D-RR) (FKG Dentaire, La Chaux-de-Fonds, Switzerland) systems. The total operating time was evaluated as the time taken to reach the working length and completely remove GP until no radiopaque remnants were observed in the final radiograph. Any GP remnants left in the canal were evaluated in terms of percentage in the whole canal. RESULTS: Rotary techniques were significantly faster and left lesser GP remnants than manual techniques (P < .05). In rotary techniques, the D-RR system was significantly faster than the PTUR system (P < .05), but there was no significant difference between them regarding GP remnants (P > .05). In manual techniques, H + X was significantly faster and left lesser GP remnants than H + SB (P < .05). CONCLUSIONS: Rotary techniques were more efficient than manual techniques in GP removal. Overall, the D-RaCe Retreatment system was most efficient, whereas manual use of H-files with System B was least efficient. However, because all the techniques showed GP remnants in the canal and radiographs failed to show these remnants, additional measures would be required to ensure complete GP removal and check for cleaner canals during endodontic retreatment. PMID- 26364004 TI - Combination of Mineral Trioxide Aggregate and Platelet-rich Fibrin Promotes the Odontoblastic Differentiation and Mineralization of Human Dental Pulp Cells via BMP/Smad Signaling Pathway. AB - INTRODUCTION: Recent reports have shown that the combined use of platelet-rich fibrin (PRF), an autologous fibrin matrix, and mineral trioxide aggregate (MTA) as root filling material is beneficial for the endodontic management of an open apex. However, the potential of the combination of MTA and PRF as an odontogenic inducer in human dental pulp cells (HDPCs) in vitro has not yet been studied. The purpose of this study was to evaluate the effect of the combination of MTA and PRF on odontoblastic maturation in HDPCs. METHODS: HDPCs extracted from third molars were directly cultured with MTA and PRF extract (PRFe). Odontoblastic differentiation of HDPCs was evaluated by measuring the alkaline phosphatase (ALP) activity, and the expression of odontogenesis-related genes was detected using reverse-transcription polymerase chain reaction or Western blot. Mineralization formation was assessed by alizarin red staining. RESULTS: HDPCs treated with MTA and PRFe significantly up-regulated the expression of dentin sialoprotein and dentin matrix protein-1 and enhanced ALP activity and mineralization compared with those with MTA or PRFe treatment alone. In addition, the combination of MTA and PRFe induced the activation of bone morphogenic proteins (BMP)/Smad, whereas LDN193189, the bone morphogenic protein inhibitor, attenuated dentin sialophosphoprotein and dentin matrix protein-1 expression, ALP activity, and mineralization enhanced by MTA and PRFe treatment. CONCLUSIONS: This study shows that the combination of MTA and PRF has a synergistic effect on the stimulation of odontoblastic differentiation of HDPCs via the modulation of the BMP/Smad signaling pathway. PMID- 26364005 TI - Developmental changes in sleep and breathing across infancy and childhood. AB - Sleep and breathing are physiological processes that begin in utero and undergo progressive change. While the major period of change for both sleep and breathing occurs during the months after birth, considered a period of vulnerability, more subtle changes continue to occur throughout childhood. The systems that control sleep and breathing develop separately, but sleep represents an activity state during which breathing and breathing control is significantly altered. Infants and young children may spend up to 12 hours a day sleeping; therefore, the effects of sleep on breathing are fundamental to understanding both processes in childhood. This review summarizes the current literature relevant to understanding the normal development of sleep and breathing across infancy and childhood. PMID- 26364006 TI - Vaccines to prevent pneumonia in children - a developing country perspective. AB - Pneumonia accounted for 15% of the 6.3 million deaths among children younger than five years in 2013, a total of approximately 935,000 deaths worldwide. Routine vaccination against common childhood illnesses has been identified as one of the most cost-effective strategies to prevent death from pneumonia. Vaccine preventable or potentially preventable diseases commonly linked with respiratory tract infections include Streptococcus pneumoniae, Haemophilus influenza type-b (Hib), pertussis, influenza, measles, and tuberculosis. Although here have been great strides in the development and administration of effective vaccines, the countries that carry the largest disease burdens still struggle to vaccinate their children and newer conjugated vaccines remain out of reach for many. The Global Vaccine Action Plan (GVAP) has identified priority areas for innovation in research in all aspects of immunisation development and delivery to ensure equitable access to vaccines for all. PMID- 26364007 TI - HIV after 40 in rural South Africa: A life course approach to HIV vulnerability among middle aged and older adults. AB - South Africa has the highest number of people living with HIV in the world (over 6 million) as well as a rapidly aging population, with 15% of the population aged 50 and over. High HIV prevalence in rural former apartheid homeland areas suggests substantial aging with HIV and acquisition of HIV at older ages. We develop a life course approach to HIV vulnerability, highlighting the rise and fall of risk and protection as people age, as well as the role of contextual density in shaping HIV vulnerability. Using this approach, we draw on an innovative multi-method data set collected within the Agincourt Health and Demographic Surveillance System in South Africa, combining survey data with 60 nested life history interviews and 9 community focus group interviews. We examine HIV risk and protective factors among adults aged 40-80, as well as how and why these factors vary among people at older ages. PMID- 26364008 TI - Health in police officers: Role of risk factor clusters and police divisions. AB - OBJECTIVE: Law enforcement is a stressful occupation associated with significant health problems. To date, most studies have focused on one specific factor or one domain of risk factors (e.g., organizational, personal). However, it is more likely that specific combinations of risk factors are differentially health relevant and further, depend on the area of police work. METHODS: A self-selected group of officers from the criminal, community, and emergency division (N = 84) of a Swiss state police department answered questionnaires assessing personal and organizational risk factors as well as mental and physical health indicators. RESULTS: In general, few differences were observed across divisions in terms of risk factors or health indicators. Cluster analysis of all risk factors established a high-risk and a low-risk cluster with significant links to all mental health outcomes. Risk cluster-by-division interactions revealed that, in the high-risk cluster, Emergency officers reported fewer physical symptoms, while community officers reported more posttraumatic stress symptoms. Criminal officers in the high-risk cluster tended to perceived more stress. Finally, perceived stress did not mediate the relationship between risk clusters and posttraumatic stress symptoms. CONCLUSION: In summary, our results support the notion that police officers are a heterogeneous population in terms of processes linking risk factors and health indicators. This heterogeneity thereby appeared to be more dependent on personal factors and individuals' perception of their own work conditions than division-specific work environments. Our findings further suggest that stress-reduction interventions that do not target job-relevant sources of stress may only show limited effectiveness in reducing health risks associated with police work. PMID- 26364009 TI - Job-loss and weight gain in British adults: Evidence from two longitudinal studies. AB - Overweight and obesity have been associated with unemployment but less is known about changes in weight associated with changes in employment. We examined weight changes associated with job-loss, retirement and maintaining employment in two samples of working adults in the United Kingdom. This was a prospective study of 7201 adults in the European Prospective Investigation of Cancer (EPIC)-Norfolk study (aged 39-76 years) and 4539 adults in the British Household Panel Survey (BHPS) who were followed up over 43 months and 26 months, respectively. In both samples, changes in measured (EPIC) and self-reported (BHPS) weight were computed for each participant and assessed in relation to three employment transitions: maintaining paid employment, retirement and job-loss. Regression models adjusted for potential confounders. Further analyses evaluated the contribution of diet, physical activity and smoking to weight gain. In EPIC-Norfolk, weight change differed across the three employment transitions for women but not men. The mean (95% CI) annualised change in weight for women who became unemployed over the follow-up period was 0.70 (0.55, 0.85) kg/y while those who maintained employment gained 0.49 (0.43, 0.55) kg/y (P = 0.007). Accounting for changes in smoking, diet and physical activity did not substantially alter the difference in weight gain among groups. In BHPS, job-loss was associated with weight gain of 1.56 (0.89, 2.23) kg/y, while those who maintained employment 0.60 (0.53, 0.68) kg/y (P < 0.001). In both samples, weight changes associated with retirement were similar to those staying in work. In BHPS, job-loss was also associated with significant declines in self-reported well-being and increases in sleep-loss. Two UK-based samples of working adults reveal strong associations between job-loss and excess weight gain. The mediating behaviours are so far unclear but psychosocial mechanisms and sleep-loss may contribute to the excess weight gain among individuals who become unemployed. PMID- 26364010 TI - Fear, blame and transparency: Obstetric caregivers' rationales for high caesarean section rates in a low-resource setting. AB - In recent decades, there has been growing attention to the overuse of caesarean section (CS) globally. In light of a high CS rate at a university hospital in Tanzania, we aimed to explore obstetric caregivers' rationales for their hospital's CS rate to identify factors that might cause CS overuse. After participant observations, we performed 22 semi-structured individual in-depth interviews and 2 focus group discussions with 5-6 caregivers in each. Respondents were consultants, specialists, residents, and midwives. The study relied on a framework of naturalistic inquiry and we analyzed data using thematic analysis. As a conceptual framework, we situated our findings in the discussion of how transparency and auditing can induce behavioral change and have unintended effects. Caregivers had divergent opinions on whether the hospital's CS rate was a problem or not, but most thought that there was an overuse of CS. All caregivers rationalized the high CS rate by referring to circumstances outside their control. In private practice, some stated they were affected by the economic compensation for CS, while others argued that unnecessary CSs were due to maternal demand. Residents often missed support from their senior colleagues when making decisions, and felt that midwives pushed them to perform CSs. Many caregivers stated that their fear of blame from colleagues and management in case of poor outcomes made them advocate for, or perform, CSs on doubtful indications. In order to lower CS rates, caregivers must acknowledge their roles as decision makers, and strive to minimize unnecessary CSs. Although auditing and transparency are important to improve patient safety, they must be used with sensitivity regarding any unintended or counterproductive effects they might have. PMID- 26364011 TI - The association of daily physical symptoms with future health. AB - RATIONALE: Daily physical symptoms play a critical role in health and illness experiences. Despite their daily prevalence, the ability of these symptoms to predict future health status is debated. OBJECTIVE: The current study examined whether physical symptom reports predict future health outcomes independent of trait measures of emotion. METHODS: Participants (N = 1189) who completed both Midlife in the United States (MIDUS) Surveys I and II as well as the National Study of Daily Experiences (NSDE) reported their daily physical symptoms at baseline and number of reported chronic conditions and functional disability nearly 10 years later. RESULTS: Physical symptoms at baseline significantly predicted the occurrence of chronic conditions and functional impairment at long term follow-up, even after adjusting for self-reported affect, self-reported health, and previous health status. CONCLUSION: Findings suggest that daily physical symptoms are unique indicators of future health status. PMID- 26364016 TI - Anal intraepithelial neoplasia among HIV-positive men who have sex with men. AB - Neoplasia is the second most common cause of mortality in HIV patients. The prevalence of anal cancer among men who have sex with men (MSM) has continued to increase since the introduction of antiretroviral therapy. We screened 94 HIV infected MSM patients. We found high-grade squamous intraepithelial lesions (HSIL) in six of the patients. The calculated prevalence of HSIL was 6.4% (95% confidence interval: 2.9-13.2). The study and implementation of screening programs for high-risk groups is a priority. PMID- 26364017 TI - Delays in diagnosis and treatment of lung cancer: Lessons from US healthcare settings. PMID- 26364018 TI - Introduction: Recommended Iron Levels for Nutritional Formulas for Infants. PMID- 26364020 TI - Balancing Benefits and Risks of Iron Fortification in Resource-Rich Countries. PMID- 26364021 TI - Balancing the Benefits and Risks of Iron Fortification in Resource-Constrained Settings. PMID- 26364019 TI - Pathophysiology of Iron Homeostasis during Inflammatory States. PMID- 26364022 TI - Iron: Current Landscape and Efforts to Address a Complex Issue in a Complex World. PMID- 26364023 TI - Postdischarge Iron Requirements of the Preterm Infant. PMID- 26364024 TI - Iron Requirements for Infants with Cow Milk Protein Allergy. PMID- 26364025 TI - Summary of Current Recommendations on Iron Provision and Monitoring of Iron Status for Breastfed and Formula-Fed Infants in Resource-Rich and Resource Constrained Countries. PMID- 26364026 TI - Expert Recommendations on Iron Fortification in Infants. PMID- 26364027 TI - Developmental Physiology of Iron Absorption, Homeostasis, and Metabolism in the Healthy Term Infant. PMID- 26364029 TI - Coagulation Factor Concentrates Fail to Restore Alterations in Fibrin Formation Caused by Rivaroxaban or Dabigatran in Studies With Flowing Blood From Treated Healthy Volunteers. AB - We evaluated the hemostatic alterations in blood from healthy individuals treated for 5 days with direct oral anticoagulants (DOACs) rivaroxaban (20 mg/d) or dabigatran (150 mg/12 h) in a single-blind clinical trial with crossover assignment (NCT01478282). We assessed the potential of prothrombin complex concentrates, activated prothrombin complex concentrates, or recombinant activated factor VII, when added ex vivo, to reverse the alterations caused by these DOACs. Blood was drawn at maximum plasma concentration after the last dose of each DOAC, and modifications in coagulation biomarkers were evaluated using a series of tests performed under steady conditions including routine coagulation, thrombin generation, and thromboelastometry assays. Additional studies in standardized flow devices were applied to evaluate alterations on platelet deposition and fibrin formation on damaged vascular surfaces exposed to flowing blood. Both DOACs caused important modifications of all coagulation biomarkers and significantly reduced fibrin formation in flow studies. Alterations in biomarkers observed in steady laboratory tests were normalized and occasionally overcompensated by procoagulant strategies. In contrast, reductions in fibrin formation observed in studies with flowing blood were improved, although never completely restored to baseline levels. Effects of dabigatran in flow studies appeared more resistant to reversal strategies than those of rivaroxaban. Inconsistencies between results of coagulation studies in steady or flowing assays not only raise concerns about the adequacy of the earlier tests to predict the restoration of the coagulopathy induced by DOACs but also suggest limitations of nonspecific procoagulant strategies to control severe coagulopathy in patients inadvertently overexposed these agents. PMID- 26364028 TI - Plant cytochrome P450s: nomenclature and involvement in natural product biosynthesis. AB - Cytochrome P450s constitute the largest family of enzymatic proteins in plants acting on various endogenous and xenobiotic molecules. They are monooxygenases that insert one oxygen atom into inert hydrophobic molecules to make them more reactive and hydro-soluble. Besides for physiological functions, the extremely versatile cytochrome P450 biocatalysts are highly demanded in the fields of biotechnology, medicine, and phytoremediation. The nature of reactions catalyzed by P450s is irreversible, which makes these enzymes attractions in the evolution of plant metabolic pathways. P450s are prime targets in metabolic engineering approaches for improving plant defense against insects and pathogens and for production of secondary metabolites such as the anti-neoplastic drugs taxol or indole alkaloids. The emerging examples of P450 involvement in natural product synthesis in traditional medicinal plant species are becoming increasingly interesting, as they provide new alternatives to modern medicines. In view of the divergent roles of P450s, we review their classification and nomenclature, functions and evolution, role in biosynthesis of secondary metabolites, and use as tools in pharmacology. PMID- 26364030 TI - Content of Zinc and Copper in Selected Plants Growing Along a Motorway. AB - In 2011 a study was carried out analyzing the effects of road traffic on bioaccumulation of zinc and copper in selected species of dicotyledonous plants growing on adjacent grasslands. To do the research the plants were sampled from the 9-km-long Siedlce bypass, a part of the international route E-30. They were collected during the flowering stage, at following distances from the road: 1, 5, 10, 15 m. The content of zinc and copper was determined with the AAS method, with dry mineralisation done before. The highest concentration of the elements, regardless of the distance from the road, was found in Taraxacum spec. Among the tested plants, the lowest zinc content was in Vicia cracca, and the lowest copper content in Rumex acetosa. The limit for copper content was exceeded in Taraxacum spec. and, slightly, in Achillea millefolium growing at the roadside, closest to the roadway. PMID- 26364031 TI - Changes in Surface Charge Density of Blood Cells in Fatal Accidental Hypothermia. AB - The objective of this research was to evaluate postmortem changes concerning electric charge of human erythrocytes and thrombocytes in fatal accidental hypothermia. The surface charge density values were determined on the basis of the electrophoretic mobility measurements of the cells conducted at various pH values of electrolyte solution. The surface charge of erythrocyte membranes after fatal accidental hypothermia increased compared to the control group within whole range of experimental pH values. Moreover, a slight shift of the isoelectric point of erythrocyte membranes towards high pH values was observed. The surface charge of thrombocyte membranes in fatal accidental hypothermia decreased at low pH compared to the control group. However, at pH range 4-9, the values increased compared to the control group. The isoelectric point of thrombocyte membranes after fatal accidental hypothermia was slightly shifted towards low pH values compared to the control group. The observed changes are probably connected with the partial destruction and functional changes of the blood cell structure. PMID- 26364032 TI - Generations of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors: Perils and Progress. AB - OPINION STATEMENT: Epidermal growth factor receptor (EGFR) mutations have been detected in approximately 10 % of North American patients diagnosed with non small cell lung cancer (NSCLC). Approximately 90 % of these mutations are exon 19 deletions or exon 21 L858R point mutations. First- and second-generation EGFR tyrosine kinase inhibitors (TKIs) are approved as first-line therapy based on clinical trials demonstrating superior response rates, progression free survival (PFS), and overall survival (OS) compared to chemotherapy in patients with EGFR mutation-positive NSCLC treated with an EGFR TKI prior to chemotherapy. However, the majority of patients treated with an EGFR TKI develop resistance to therapy within about 12 months, approximately 50 % of patients due to a second site mutation, the T790M mutation occurring within exon 20. At the time of progression, the EGFR TKI is most commonly discontinued and a different systemic therapy is initiated. However, oncogene addiction persists and recent exciting data with third-generation EGFR TKIs suggests that acquired resistance may be surmountable. The newest EGFR TKIs have shown activity against EGFR-mutant NSCLC after progression on first-generation TKIs, including those with T90M, while sparing wild-type EGFR and hence appear to be both well tolerated and efficacious. At this time, it appears that third-generation EGFR TKIs are effective following first-generation therapy, and determining the most appropriate sequence to maximize overall survival is a matter of ongoing investigation. As the arsenal of active agents in EGFR mutant NSCLC grows, future research into potential combinations, optimal timing, and resistance mechanisms of these new treatments, as well as their possible role in the adjuvant, post chemoradiation, and neoadjuvant settings holds great promise for this group of patients. PMID- 26364033 TI - Morphometric variability of pyramidalis muscle and its clinical significance. AB - PURPOSE: The goal of the study is to analyze the morphometric diversity of the pyramidalis muscle (PM) and to evaluate how it is affected by gender and side of occurrence. MATERIALS AND METHODS: Ninety-six (50 male and 46 female) formalin embalmed Greek cadavers were dissected. RESULTS: The PM was present in 93.8 %, usually bilaterally (79.2 %) than unilaterally (14.6 %) (p = 0.003) and more frequently in females (91.3 %) than in males (68 %) (p = 0.0001). Side symmetry was detected. The mean length of PM in males and females was 8.37 +/- 2.80 and 6.18 +/- 1.64 cm on the right and 7.50 +/- 2.66 and 6.56 +/- 1.68 cm on the left side. Male predominance existed on the right and left-sided PM lengths (p = 0.0001 and p = 0.054). The mean width of the right-sided PMs in males and females was 1.61 +/- 0.55 and 1.50 +/- 0.44 cm and the left-sided 1.56 +/- 0.53 and 1.55 +/- 0.38 cm without gender dimorphism. The positive correlation between the PM length and width indicates a symmetrical muscle augmentation on the two dimensions. CONCLUSIONS: The study demonstrates that the PM is almost constant in Greeks. Among populations the muscle morphometric variability, its clinical significance and its variable uses will help surgeons when intervening in the lower abdominal wall. PMID- 26364034 TI - A morphometric analysis of the superior cervical ganglion and its surrounding structures. AB - PURPOSE: The aim of this cadaveric study was to detect the superior cervical ganglion (SCG) in a topographic manner according to vertebrae and to determine the relationship between the vertebrae, mandibular angle and longus colli muscle through morphometric analysis. METHODS: The present study was performed on 40 SCG of 20 human cadavers (16 males, 4 females). The level of the SCG was determined based on the vertebrae. Ganglion length, width and thickness were detected. Distance to the adjacent vertebra, the mandibular angle and medial side of the longus colli muscle were measured. The results were evaluated statistically. RESULTS: The SCG existing in all cadavers was detected at the C2 vertebra level in 34 cadavers and at the C3 vertebra level in 6 cadavers. The average length, width and thickness of the SCG were 15.18 +/- 1.12, 4.62 +/- 0.25, and 1.83 +/- 0.10 mm, respectively. No statistically significant difference was detected in terms of the distances between the ganglion and anterior tubercle of transverse processes of the vertebrae as well as the mandibular angle on either side. The distance between the SCG and the medial edge of the longus colli muscle was significantly greater on the left side in both men (p < 0.001) and women (p < 0.01). CONCLUSION: Recognition of morphometric characteristics of the SCG and detection of its location according to adjacent formations may serve as a guide for nerve blockage studies and help surgeons to preserve the ganglion in both anterior and anterolateral cervical approaches. PMID- 26364040 TI - Relationships between maximum temperature and heat-related illness across North Carolina, USA. AB - Heat kills more people than any other weather-related event in the USA, resulting in hundreds of fatalities each year. In North Carolina, heat-related illness accounts for over 2,000 yearly emergency department admissions. In this study, data on emergency department (ED) visits for heat-related illness (HRI) were obtained from the North Carolina Disease Event Tracking and Epidemiologic Collection Tool to identify spatiotemporal relationships between temperature and morbidity across six warm seasons (May-September) from 2007 to 2012. Spatiotemporal relationships are explored across different regions (e.g., coastal plain, rural) and demographics (e.g., gender, age) to determine the differential impact of heat stress on populations. This research reveals that most cases of HRI occur on days with climatologically normal temperatures (e.g., 31 to 35 degrees C); however, HRI rates increase substantially on days with abnormally high daily maximum temperatures (e.g., 31 to 38 degrees C). HRI ED visits decreased on days with extreme heat (e.g., greater than 38 degrees C), suggesting that populations are taking preventative measures during extreme heat and therefore mitigating heat-related illness. PMID- 26364042 TI - Could cigarette packaging be used as a tool to make prevention of smoke-induced respiratory diseases? AB - The most important consequences of smoking are chronic obstructive pulmonary disease (COPD) and lung cancer (LC). Although the use of shocking images and warning messages on cigarette packaging is a valid tool of smoke dishabituation, unfortunately, millions of people go on smoking. Our hypotheses is that cigarette packet covers could also be used to give further messages, especially meant to spur also a screening of smoke-induced respiratory diseases. Messages on cigarette packaging suggesting smokers to perform a spirometry and a chest X-ray may persuade them not only to quit their habit but also to have a screening for COPD and LC prevention. If our hypotheses is taken into account it will have a strong worldwide impact. PMID- 26364041 TI - A Dose-Finding Study of Dexketoprofen in Patients Undergoing Laparoscopic Cholecystectomy: A Randomized Clinical Trial on Effects on the Analgesic Concentration of Oxycodone. AB - BACKGROUND: Dexketoprofen has been shown to provide efficient analgesia and an opioid-sparing effect after orthopedic surgery. In this dose-finding study, we evaluated the analgesic efficacy and opioid-sparing effect of dexketoprofen administered intravenously (i.v.) after laparoscopic cholecystectomy (LCC). METHODS: Twenty-four patients undergoing LCC were randomized to receive dexketoprofen 10 or 50 mg i.v. 15 min before the end of the surgery. Subjects were provided with 0.2 mg/kg of oxycodone at anesthesia induction. In the recovery room, pain was assessed with an 11-point numerical rating scale (NRS; score of 0 = no pain, score of 10 = most severe pain) every 10 min. When the NRS score was >=3/10 at rest or >=5/10 at wound compression, a plasma sample was taken for analysis of oxycodone [to determine the minimum effective concentration (MEC)], its metabolites, and dexketoprofen. After that, subjects were titrated with oxycodone 2 or 3 mg i.v. every 10 min until the NRS score was <3/10 at rest and <5/10 at wound compression. At this point, a second plasma sample was taken for analysis of oxycodone [minimum effective analgesic concentration (MEAC)], its metabolites, and dexketoprofen. RESULTS: At the onset of pain, the plasma oxycodone concentrations (MEC) were similar in the two groups: median 60 ng/mL (range 37-73) in the 10 mg group and median 52 ng/mL (range 24-79) in the 50 mg group. At the time of pain relief, the MEACs were 98 ng/mL (range 59-150) in the 10 mg group and 80 ng/mL (range 45-128) in the 50 mg group. The total doses of oxycodone needed to achieve pain relief were similar: 0.11 mg/kg (range 0-0.33) in the 10 mg group and 0.08 mg/kg (range 0-0.24) in the 50 mg group. Eleven subjects developed mild desaturation or a decreased respiratory rate after oxycodone titration. CONCLUSION: In the present double-blinded, randomized clinical trial, the need for a rescue opioid analgesic, oxycodone, was similar with the two dose levels of dexketoprofen-10 and 50 mg i.v.-after LCC. PMID- 26364043 TI - Dietary modifications in Parkinson's disease: A neuroprotective intervention? AB - Parkinson's disease (PD) is the second most common neurodegenerative disease, with the prevalence increasing as the population ages. Many mechanisms have been implicated in the pathogenesis of PD including oxidative stress, mitochondrial dysfunction, protein aggregation, and inflammation. Current treatment strategies focus on symptomatic improvement. However, therapies to modify disease progression are lacking. A whole food, plant-based diet contains many compounds that fight oxidative stress and inflammation. Evidence from animal models show that various phytochemicals may alter the mechanisms contributing to PD pathophysiology. Epidemiological studies show a relationship between reduced risk of PD and diet. We hypothesize that phytochemicals in plant-based foods may contribute to neuroprotection in PD and that adopting a plant-based diet may provide symptomatic improvement and alter disease progression in PD. PMID- 26364044 TI - Fracture healing redefined. AB - It is well established that local mechanical conditions and interfragmentary movement are important factors for successful bone healing and may vary dramatically with patient fracture-load and activity. Up until now however it was technically impossible to use these key influence parameters in the aftercare treatment process of human lower extremity fractures. We propose a theory that with state of the art sensor technology these biomechanical influences can not only be monitored in vivo, but also used for individualized therapy protocols. Local measurement systems for fracture healing are available but remain research tools, due to various technical issues. To investigate the biomechanical influences on healing right away surrogate sensor tools are needed. Various gait characteristics have been proposed as surrogate measures. Currently available sensor tools could be modified with the appropriate support structure to allow such measurements continuously over the course of a fracture healing. Interdisciplinary work between clinicians, software engineers with computer and biomechanical simulations is needed. Through such a sensor system human boundary conditions for fracture healing could not only be defined for the first time, but also used for a unique, extendible aftercare system. With this tool critical healing situations would be detected much earlier and could be prevented with easy activity modifications, reducing patient and socioeconomic burden of disease. The hypothesis, necessary tools and support structures are presented. PMID- 26364045 TI - Wheat-based foods and non celiac gluten/wheat sensitivity: Is drastic processing the main key issue? AB - While gluten and wheat must be absolutely avoided in coeliac disease and allergy, respectively, nutritional recommendations are largely more confused about non coeliac wheat/gluten sensitivity (NCWGS). Today, some even recommend avoiding all cereal-based foods. In this paper, the increased NCWGS prevalence is hypothesized to parallel the use of more and more drastic processes applied to the original wheat grain. First, a parallel between gluten-related disorders and wheat processing and consumption evolution is briefly proposed. Notably, increased use of exogenous vital gluten is considered. Drastic processing in wheat technology are mainly grain fractionation and refining followed by recombination and salt, sugars and fats addition, being able to render ultra-processed cereal-based foods more prone to trigger chronic low-grade inflammation. Concerning bread, intensive kneading and the choice of wheat varieties with high baking quality may have rendered gluten less digestible, moving digestion from pancreatic to intestinal proteases. The hypothesis of a gluten resistant fraction reaching colon and interacting with microflora is also considered in relation with increased inflammation. Besides, wheat flour refining removes fiber co-passenger which have potential anti-inflammatory property able to protect digestive epithelium. Finally, some research tracks are proposed, notably the comparison of NCWGS prevalence in populations consuming ultra-versus minimally-processed cereal-based foods. PMID- 26364046 TI - An epigenetic basis for autism spectrum disorder risk and oral contraceptive use. AB - In the United States 1 in 68 children are diagnosed with autism spectrum disorder (ASD). Although the etiology is unknown, many scientists believe ASD is caused by a combination of genetic and environmental factors and/or epigenetic factors. The widespread use of oral contraceptives is one environmental risk factor that has been greatly overlooked in the biomedical literature. Oral contraceptives, synthetic hormones created to imitate natural human hormones and disrupt endogenous endocrine function to inhibit pregnancy, may be causing the harmful neurodevelopmental effects that result in the increased prevalence of ASD. It is conceivable that the synthetic hormones repeatedly assault the oocyte causing persistent changes in expression of the estrogen receptor beta gene. Ethinylestradiol, a known endocrine disruptor, may trigger DNA methylation of the estrogen receptor beta gene causing decreased mRNA resulting in impaired brain estrogen signaling in progeny. In addition, it is possible the deleterious effects are transgenerational as the estrogen receptor gene and many of its targets may be imprinted and the methylation marks protected from global demethylation and preserved through fertilization and beyond to progeny generations. This article will delineate the hypothesis that ethinylestradiol activates DNA methylation of the estrogen receptor beta gene causing decreased mRNA resulting in diminished brain estrogen signaling in offspring of mothers exposed to oral contraceptives. Considering the detrimental epigenetic and transgenerational effects proposed, it calls for further study. PMID- 26364047 TI - Preventing in-stent restenosis using lipoprotein (a), lipid and cholesterol adsorbent materials. AB - Atherosclerosis is one of the major cause of mortality in developed countries. The characteristic lesion of atherosclerosis is the atheroma or plaque that forms through thickening of the inner layer of the vessel wall (called the intima). The development of stent in 1980s revolutionised treatment of cardiovascular diseases, including atherosclerosis. However the advent of stenting was hindered by the new problem of in-stent restenosis. It was demonstrated that in-stent restenosis was the result of a new pathology in the form of neointimal hyperplasia, which was a maladaptive healing response to bare-metal stent implantation. Recent evidence suggests that although drug-eluting stent (DES) have reduced restenosis rates, important concerns have been raised regarding increased late stent thrombosis, myocardial infarction and death. With advances in nanotechnology and smart materials, covered stents has been proposed to overcome this problem. This is due to in-stent late restenosis and thromboses are mainly caused by smooth muscle cells (SMC) proliferation. Studies showed that there is a relation between high low-density lipoprotein (LDL) and lipoprotein (a) [Lp(a)] level in blood stream and chance of in-stent restenosis, moreover studies show that Lp(a) could stimulate SMC proliferation. We hypothesis development of covered stent with novel design and use of smart materials which could adsorb cholesterol and prevent contact between Lp(a) and vessel wall to overcome problem indicated in DES. In addition cost of stents will significantly reduce by elimination of drugs as well as complex manufacturing of the drug incorporation. PMID- 26364048 TI - Rhizobium helianthi sp. nov., isolated from the rhizosphere of sunflower. AB - A Gram-stain-negative, non-spore-forming, rod-shaped and aerobic bacterium, designated Xi19T, was isolated from a soil sample collected from the rhizosphere of sunflower (Helianthus annuus) in Wuyuan county of Inner Mongolia, China and was characterized taxonomically by using a polyphasic approach. Phylogenetic analysis based on 16S rRNA gene sequences indicated that the novel isolate was related to species of the genus Rhizobium, sharing the greatest 16S rRNA gene sequence similarity with Rhizobium rhizoryzae J3-AN59T (98.4 %), followed by Rhizobium pseudoryzae J3-A127T (97.4 %). There were low similarities ( < 91 %) between the atpD, recA and glnII gene sequences of the novel strain and those of members of the genus Rhizobium. DNA-DNA hybridization values between strain Xi19T and the most related strain Rhizobium rhizoryzae J3-AN59T were low. The major cellular fatty acids of strain Xi19T were C16 : 0, summed feature 8 (C18 : 1omega7c and/or C18 : 1omega6c) and C19 : 0 cyclo omega8c. Q-10 was identified as the predominant ubiquinone and the major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and phosphatidylcholine. The DNA G+C content of strain Xi19T was 60.2 mol%. On the basis of physiological and biochemical characteristics, coupled with genotypic data obtained in this work, strain Xi19T represents a novel species of the genus Rhizobium, for which the name Rhizobium helianthi is proposed. The type strain is Xi19T ( = CGMCC 1.12192T = KCTC 23879T). PMID- 26364049 TI - Relationship of metabolic and endocrine parameters to brain glucose metabolism in older adults: do cognitively-normal older adults have a particular metabolic phenotype? AB - Our primary objective in this study was to quantify whole brain and regional cerebral metabolic rates of glucose (CMRg) in young and older adults in order to determine age-normalized reference CMRg values for healthy older adults with normal cognition for age. Our secondary objectives were to--(i) report a broader range of metabolic and endocrine parameters including body fat composition that could form the basis for the concept of a 'metabolic phenotype' in cognitively normal, older adults, and (ii) to assess whether medications commonly used to control blood lipids, blood pressure or thyroxine affect CMRg values in older adults. Cognition assessed by a battery of tests was normal for age and education in both groups. Compared to the young group (25 years old; n = 34), the older group (72 years old; n = 41) had ~14% lower CMRg (MUmol/100 g/min) specifically in the frontal cortex, and 18% lower CMRg in the caudate. Lower grey matter volume and cortical thickness was widespread in the older group. These differences in CMRg, grey matter volume and cortical thickness were present in the absence of any known evidence for prodromal Alzheimer's disease (AD). Percent total body fat was positively correlated with CMRg in many brain regions but only in the older group. Before and after controlling for body fat, HOMA2-IR was significantly positively correlated to CMRg in several brain regions in the older group. These data show that compared to a healthy younger adult, the metabolic phenotype of a cognitively-normal 72 year old person includes similar plasma glucose, insulin, cholesterol, triglycerides and TSH, higher hemoglobin A1c and percent body fat, lower CMRg in the superior frontal cortex and caudate, but the same CMRg in the hippocampus and white matter. Age-normalization of cognitive test results is standard practice and we would suggest that regional CMRg in cognitively healthy older adults should also be age-normalized. PMID- 26364051 TI - Evaluation of applied public health emergency system at Prince Mohammed International Airport in Almedinah during Hajj season 2014: a qualitative case study. AB - BACKGROUND: During the Hajj season 2014, several public health measures were applied by the Ministry of Health at Prince Mohammed International Airport in Almedinah. However, several operational defects affected the provision of preventive health services for passengers and airport workers. This study aims to evaluate the applied public health emergency system at the airport, detect any potential gaps and to provide appropriate operational solutions. METHODS: This is a qualitative case study conducted at Prince Mohammed International Airport in Almedinah during the 2014 Hajj season, September 2014. Data were collected via semi-structured interviews, focus groups and policy document reviews. Interviews were conducted with the 14 individuals of the airport's decision makers and relevant health practitioners. Data were recorded via taking notes during interviews and data coding was performed to produce the main themes and subthemes of the study. RESULTS: The main findings of the study revealed three main defects affecting the applied public health emergency system at the airport. The main themes were mainly related to shortage in logistics related to public health emergency systems, shortage in proper documentation of policies and lack of documented protocols of communications among airport stakeholders. CONCLUSIONS: The study highlighted the main factors hindering the application of public health emergency measures at the airport. A Public Health Emergency Contingency Plan was proposed as a method to regulate the process of providing logistics for public health preventive services, the method of producing documented policies and methods of producing Memoranda of Understandings as communication regulators. PMID- 26364050 TI - Some Operational Characteristics of Glycine Release in Rat Retina: The Role of Reverse Mode Operation of Glycine Transporter Type-1 (GlyT-1) in Ischemic Conditions. AB - Rat posterior eyecups containing the retina were prepared, loaded with [(3)H]glycine and superfused in order to determine its release originated from glycinergic amacrine cells and/or glial cells. Deprivation of oxygen and glucose from the Krebs-bicarbonate buffer used for superfusion evoked a marked increase of [(3)H]glycine release, an effect that was found to be external Ca(2+) independent. Whereas oxygen and glucose deprivation increased [(3)H]glycine release, its uptake was reduced suggesting that energy deficiency shifts glycine transporter type-1 operation from normal to reverse mode. The increased release of [(3)H]glycine evoked by oxygen and glucose deprivation was suspended by addition of the non-competitive glycine transporter type-1 inhibitor NFPS and the competitive inhibitor ACPPB further suggesting the involvement of this transporter in the mediation of [(3)H]glycine release. Oxygen and glucose deprivation also evoked [(3)H]glutamate release from rat retina and the concomitantly occurring release of the NMDA receptor agonist glutamate and the coagonist glycine makes NMDA receptor pathological overstimulation possible in hypoxic conditions. [(3)H]Glutamate release was suspended by addition of the excitatory amino acid transporter inhibitor TBOA. Sarcosine, a substrate inhibitor of glycine transporter type-1, also increased [(3)H]glycine release probably by heteroexchange shifting transporter operation into reverse mode. This effect of sarcosine was also external Ca(2+)-independent and could be suspended by NFPS. Energy deficiency in retina induced by ouabain, an inhibitor of the Na(+)-K(+)-dependent ATPase, and by rotenone, a mitochondrial complex I inhibitor added with the glycolytic inhibitor 2-deoxy-D-glucose, led to increase of retinal [(3)H]glycine efflux. These effects of ouabain and rotenone/2-deoxy-D-glucose could also be blocked by NFPS pointed to the preferential reverse mode operation of glycine transporter type-1 as a consequence of impaired cellular energy homeostasis. Immunohistochemical studies revealed that glycine transporter type 1, of which reverse mode operation assures [(3)H]glycine release, is expressed in amacrine cells in the inner nuclear and plexiform layers of the retina and also in Muller macroglia cells. We conclude that disruption of the balanced normal/reverse mode operation of glycine transporter type-1 is likely a significant factor contributing to neurotoxic processes of the retina. The possibility to inhibit glycine transporter type-1 mediated glycine efflux by drugs more potently than glycine uptake might offer some therapeutic potential for the treatment of various neurodegenerative disorders of the retina. PMID- 26364052 TI - Do tanning salons adhere to new legal regulations? Results of a simulated client trial in Germany. AB - In August 2009 and January 2012, two regulations were passed in Germany to limit UV exposure in the general population. These regulations state that no minors are allowed to use tanning devices. Personnel of tanning salons is mandated to offer counseling regarding individual skin type, to create a dosage plan with the customer and to provide a list describing harmful effects of UV radiation. Furthermore, a poster of warning criteria has to be visible and readable at all times inside the tanning salon. It is unclear whether these regulations are followed by employees of tanning salons in Germany, and we are not aware of any studies examining the implementation of the regulations at individual salons. We performed a simulated client study visiting 20 tanning salons in the city-state of Bremen in the year 2014, using a short checklist of criteria derived from the legal requirements, to evaluate whether legal requirements were followed or not. We found that only 20 % of the tanning salons communicated adverse health effects of UV radiation in visible posters and other materials and that only 60 % of the salons offered the required determination of the skin type to customers. In addition, only 60 % of the salons offered to complete the required dosage plan with their customers. To conclude, our results suggest that the new regulations are insufficiently implemented in Bremen. Additional control mechanisms appear necessary to ensure that consumers are protected from possible carcinogenic effects of excessive UV radiation. PMID- 26364053 TI - Barriers to Access of Primary Healthcare by Immigrant Populations in Canada: A Literature Review. AB - To summarize information obtained from original research about barriers to access of primary healthcare by Canadian immigrants' and to identify research gaps. Electronic databases of primary research articles and grey literature were searched without restricting the time period. The preferred reporting items for systematic reviews and meta-analyses statement was followed for literature selection. Articles were selected based on three criteria: (a) the study population was Canadian legal immigrant(s), (b) the research was about the barriers to accessing primary healthcare in Canada, and (c) the article was written in English. Relevant information from the articles was extracted into tabular format and classified for thematic analysis. Identified barriers were grouped into five themes: cultural, communication, socio-economic status, healthcare system structure and immigrant knowledge. The barriers to accessing primary healthcare in each of these categories can provide insight and subsequent direction for changes needed to improve immigrant care and mitigate their deterioration in health status. The demographic and ethno-cultural distributions of the study populations across the provinces highlight the need to expand research to encompass more varied immigrant groups across more regions of Canada, including more research on male immigrants and immigrant seniors, and to increase research related to health care providers' perspectives on the barriers. PMID- 26364055 TI - Chemical shift assignments of the fibronectin III like domains 7-8 of type VII collagen. AB - Type VII collagen (Col7) is important for skin stability. This is underlined by the severe skin blistering phenotype in the Col7 related diseases dystrophic epidermolysis bullosa and epidermolysis bullosa acquisita (EBA). Col7 has a large N-terminal non-collagenous domain (NC1) that is followed by the triple helical collagenous domain. The NC1 domain has subdomains with homology to adhesion molecules and mediates important interactions within the extracellular matrix. An 185 amino acid long part of the NC1-subdomain termed fibronectin III like domains 7 and 8 (FNIII7-8) was investigated. Antibodies against this region are pathogenic in a mouse model of EBA and one reported missense mutations of Col7 lies within these domains. The nearly complete NMR resonance assignment of recombinant FNIII7-8 of Col7 is reported. PMID- 26364054 TI - Latent Tuberculosis Infection Among Immigrant and Refugee Children Arriving in the United States: 2010. AB - Immigrants and refugees age 2-14 years entering the United States from countries with estimated tuberculosis (TB) incidence rate >=20 per 100,000 population are screened for TB. Children with TB disease are treated before US arrival. Children with positive tuberculin skin tests (TST), but negative TB evaluation during their pre-immigration examination, are classified with latent TB infection (LTBI) and are recommended for re-evaluation post-arrival. We examined post-immigration TB evaluation and therapy for children arriving with LTBI. We reviewed medical exam data from immigrant children with medical conditions and all refugee children arriving during 2010. Medical examination data were available for 67,334 children. Of these, 8231 (12 %) had LTBI pre-immigration; 5749 (70 %) were re evaluated for TB post-immigration, and 64 % were retested by TST or IGRA. The pre immigration LTBI diagnosis was changed for 38 % when retested by TST and for 71 % retested by IGRA. Estimated LTBI therapy initiation and completion rates were 68 and 12 %. In this population, testing with IGRA may limit the number of children targeted for therapy. Increased pre-immigration TB screening with post immigration follow-up evaluation leading to completion of LTBI therapy should be encouraged to prevent TB reactivation. PMID- 26364056 TI - Backbone and side-chain resonance assignment of the A147T polymorph of mouse TSPO in complex with a high-affinity radioligand. AB - The integral polytopic membrane protein TSPO is the target for numerous endogenous and synthetic ligands. However, the affinity of many ligands is influenced by a common polymorphism in TSPO, in which an alanine at position 147 is replaced by threonine, thereby complicating the use of several radioligands for clinical diagnosis. In contrast, the best-characterized TSPO ligand (R) PK11195 binds with similar affinity to both variants of mitochondrial TSPO (wild type and A147T variant). Here we report the (1)H, (13)C, (15)N backbone and side chain resonance assignment of the A147T polymorph of TSPO from Mus Musculus in complex with (R)-PK11195 in DPC detergent micelles. More than 90 % of all resonances were sequence-specifically assigned, demonstrating the ability to obtain high-quality spectral data for both the backbone and the side-chains of medically relevant integral membrane proteins. PMID- 26364057 TI - Gene mutations in gastric cancer: a review of recent next-generation sequencing studies. AB - Gastric cancer (GC) is one of the most common malignancies worldwide. Although some driver genes have been identified in GC, the molecular compositions of GC have not been fully understood. The development of next-generation sequencing (NGS) provides a high-throughput and systematic method to identify all genetic alterations in the cancer genome, especially in the field of mutation detection. NGS studies in GC have discovered some novel driver mutations. In this review, we focused on novel gene mutations discovered by NGS studies, along with some well known driver genes in GC. We organized mutated genes from the perspective of related biological pathways. Mutations in genes relating to genome integrity (TP53, BRCA2), chromatin remodeling (ARID1A), cell adhesion (CDH1, FAT4, CTNNA1), cytoskeleton and cell motility (RHOA), Wnt pathway (CTNNB1, APC, RNF43), and RTK pathway (RTKs, RAS family, MAPK pathway, PIK pathway) are discussed. Efforts to establish a molecular classification based on NGS data which is valuable for future targeted therapy for GC are introduced. Comprehensive dissection of the molecular profile of GC cannot only unveil the molecular basis for GC but also identify genes of clinical utility, especially potential and specific therapeutic targets for GC. PMID- 26364059 TI - Efficacy of water- and oil-in-water-formulated Metarhizium anisopliae in Rhipicephalus sanguineus eggs and eclosing larvae. AB - Conidia of the entomopathogenic fungus Metarhizium anisopliae (Ascomycota: Clavicipitaceae) were assessed against Rhipicephalus sanguineus (Arachnida: Ixodidae) eggs under laboratory conditions. Clusters of 25 eggs were applied either directly with the fungal conidial formulations or set on previously fungus treated filter paper. Treatments consisted of conidia formulated in water or an oil-in-water emulsion at final concentrations of 3.3 * 10(3), 10(4), 3.3 * 10(4), 10(5), or 3.3 * 10(5) conidia/cm(2). The development of mycelium and new conidia on egg clusters incubated at 25 degrees C and humidity close to saturation depended on conidial concentration, formulation, and application technique. No larvae eclosed from eggs after direct applications of conidia regardless of the formulation. The eclosion and survival of larvae from indirectly treated egg clusters depended on the type of formulation and conidial concentration applied. Oil-in-water formulations of conidia demonstrated the highest activity against eggs of R. sanguineus. PMID- 26364058 TI - Metabolomic approach to profile functional and metabolic changes in heart failure. AB - BACKGROUND: Heart failure (HF) is characterized by a series of adaptive changes in energy metabolism. The use of metabolomics enables the parallel assessment of a wide range of metabolites. In this study, we appraised whether metabolic changes correlate with HF severity, assessed as an impairment of functional contractility, and attempted to interpret the role of metabolic changes in determining systolic dysfunction. METHODS: A 500 MHz proton nuclear magnetic resonance ((1)H-NMR)-based analysis was performed on blood samples from three groups of individuals: 9 control subjects (Group A), 9 HF patients with mild to moderate impairment of left ventricle ejection fraction (LVEF: 41.9 +/- 4.0 %; Group B), and 15 HF patients with severe LVEF impairment (25.3 +/- 10.3 %; Group C). In order to create a descriptive model of HF, a supervised orthogonal projection on latent structures discriminant analysis (OPLS-DA) was applied using speckle tracking-derived longitudinal strain rate as the Y-variable in the multivariate analysis. RESULTS: OPLS-DA identified three metabolic clusters related to the studied groups achieving good values for R(2) [R(2)(X) = 0.64; R(2)(Y) = 0.59] and Q(2) (0.39). The most important metabolites implicated in the clustering were 2-hydroxybutyrate, glycine, methylmalonate, and myo-inositol. CONCLUSIONS: The results demonstrate the suitability of metabolomics in combination with functional evaluation techniques in HF staging. This innovative tool should facilitate investigation of perturbed metabolic pathways in HF and their correlation with the impairment of myocardial function. PMID- 26364061 TI - The artery of Adamkiewicz: More interesting than practical? PMID- 26364060 TI - Insomnia in the Military: Application and Effectiveness of Cognitive and Pharmacologic Therapies. AB - Insomnia is one of the most common complaints of US armed service members. Diagnosis and treatment of insomnia in active duty and veteran populations are often complicated by comorbid disorders experienced by military personnel, such as post-traumatic stress disorder (PTSD) and traumatic brain injury (TBI). Cognitive behavioral therapy for insomnia (CBTi), pharmacologic interventions, and alternative therapies are discussed as relevant to their applications within military populations. Future directions in research are suggested. PMID- 26364062 TI - Aspirin resistance: A role in left ventricular assist device thrombosis? PMID- 26364063 TI - Surgery meets fluid dynamics: Into the vortex. PMID- 26364064 TI - Gospel of the guidelines. PMID- 26364065 TI - Integrating LIDAR and forest inventories to fill the trees outside forests data gap. AB - Forest inventories are commonly used to estimate total tree biomass of forest land even though they are not traditionally designed to measure biomass of trees outside forests (TOF). The consequence may be an inaccurate representation of all of the aboveground biomass, which propagates error to the outputs of spatial and process models that rely on the inventory data. An ideal approach to fill this data gap would be to integrate TOF measurements within a traditional forest inventory for a parsimonious estimate of total tree biomass. In this study, Light Detection and Ranging (LIDAR) data were used to predict biomass of TOF in all "nonforest" Forest Inventory and Analysis (FIA) plots in the state of Maryland. To validate the LIDAR-based biomass predictions, a field crew was sent to measure TOF on nonforest plots in three Maryland counties, revealing close agreement at both the plot and county scales between the two estimates. Total tree biomass in Maryland increased by 25.5 Tg, or 15.6%, when biomass of TOF were included. In two counties (Carroll and Howard), there was a 47% increase. In contrast, counties located further away from the interstate highway corridor showed only a modest increase in biomass when TOF were added because nonforest conditions were less common in those areas. The advantage of this approach for estimating biomass of TOF is that it is compatible with, and explicitly separates TOF biomass from, forest biomass already measured by FIA crews. By predicting biomass of TOF at actual FIA plots, this approach is directly compatible with traditionally reported FIA forest biomass, providing a framework for other states to follow, and should improve carbon reporting and modeling activities in Maryland. PMID- 26364066 TI - Identification and characterization of odorous gas emission from a full-scale food waste anaerobic digestion plant in China. AB - Odorous gas emission characteristic along with the successive processes of a typical full-scale food waste (FW) anaerobic digestion plant in China was investigated in September and January. Seasonal variations in pollutant concentration and principal component analysis (PCA) showed markedly different characteristics between the two months. However, the main reason for the seasonal difference at the sorting process differed from the reason for the seasonal difference at other treatment units. Most odorous volatile organic compound (VOC) concentrations tested near an anaerobic digestion tank were similar and low in both months. Odor indices, including odor contribution (OC) and odor activity value (OAV) of various odorants, were further calculated to evaluate the malodor degree and contribution to the nuisance smell of any odorant. Brought about by people's different dietary habits, H2S and sulfocompounds were found to be dominant contributors to the large total OVA in the January test. By contrast, oxygenated organic compounds played an important role on the sum of OVA in September. PMID- 26364067 TI - Invited Commentary: Professional Autonomy, Self-Regulation and Quality Improvement. PMID- 26364068 TI - Lobectomy by Video-Assisted Thoracic Surgery or Muscle-Sparing Thoracotomy for Stage 1 Lung Cancer: Could Cost-Effectiveness Give the Answer? PMID- 26364069 TI - Video-Assisted Thoracic Surgery vs Muscle-Sparing Thoracotomy: Prioritizing Randomized Trial to Assess Complications and Long-Term Survival over Cost Comparisons: In Reply to Spartalis and colleagues. PMID- 26364070 TI - Effectiveness of Minocycline/Rifampin vs Chlorhexidine/Silver Sulfadiazine Impregnated Central Venous Catheters. PMID- 26364072 TI - The Natural History of Multinodular Goiter. PMID- 26364071 TI - Preventing Central Line-Associated Bloodstream Infection: In Reply to Mermel. PMID- 26364074 TI - On the 2D-transition, hysteresis and thermodynamic equilibrium of Kr adsorption on a graphite surface. AB - The adsorption and desorption of Kr on graphite at temperatures in the range 60 88K, was systematically investigated using a combination of several simulation techniques including: Grand Canonical Monte Carlo (GCMC), Canonical kinetic-Monte Carlo (C-kMC) and the Mid-Density Scheme (MDS). Particular emphasis was placed on the gas-solid, gas-liquid and liquid-solid 2D phase transitions. For temperatures below the bulk triple point, the transition from a 2D-liquid-like monolayer to a 2D-solid-like state is manifested as a sub-step in the isotherm. A further increase in the chemical potential leads to another rearrangement of the 2D-solid like state from a disordered structure to an ordered structure that is signalled by (1) another sub-step in the monolayer region and (2) a spike in the plot of the isosteric heat versus density at loadings close to the dense monolayer coverage concentration. Whenever a 2D transition occurs in a grand canonical isotherm it is always associated with a hysteresis, a feature that is not widely recognised in the literature. We studied in details this hysteresis with the analysis of the canonical isotherm, obtained with C-kMC, which exhibits a van der Waals (vdW) type loop with a vertical segment in the middle. We complemented the hysteresis loop and the vdW curve with the analysis of the equilibrium transition obtained with the MDS, and found that the equilibrium transition coincides exactly with the vertical segment of the C-kMC isotherm, indicating the co existence of two phases at equilibrium. We also analysed adsorption at higher layers and found that the 2D-coexistence is also observed, provided that the temperature is well below the triple point. Finally the 2D-critical temperatures were obtained for the first three layers and they are in good agreement with the experimental data in the literature. PMID- 26364075 TI - Semifluorinated thiols in Langmuir monolayers - a study by nonlinear and linear vibrational spectroscopies. AB - A series of semifluorinated thiols of the general formula CmF2m+1CnH2nSH (abbr. FmHnSH) have been synthesized and characterized in Langmuir monolayers with surface pressure-area isotherms, complemented with polarization-modulated reflection absorption spectroscopy (PM-IRRAS) and sum-frequency generation (SFG) techniques. A comparative analysis was performed for compounds having the same length of fluorinated segment (F10) and variable length of the hydrogenated part (H6, H10, H12), and having identical hydrogenated segment (H12) connected to a fluorinated moiety of different lengths (F6, F8, F10). For the sake of comparison, an alkanethiol (H18SH) was also examined, and F10H10COOH and F10H10OH molecules were used for helping the assignment of SFG spectra of CH stretches. SFG was applied to investigate the hydrocarbon chain and the terminal CF3 group, while PM-IRRAS was used to probe CF2 groups. The number of gauche defects in the hydrocarbon chain increased with the increasing length of the molecule, either by elongation of the hydrogenated or perfluorinated part. SFG measurements recorded at three polarization combinations (ppp, ssp, sps) enabled us to estimate the tilt angle of the terminal CF3 group in semifluorinated thiol molecules as ranging from 35 degrees to 45 degrees , which is consistent with nearly vertical fluorinated segments. Upon increasing the surface pressure, the fluorinated segment gets slightly more upright, but the hydrocarbon chain tilt increases while keeping the same average number of gauche defects. The extent of disorder in the hydrogenated segment may be controlled by varying the size of the fluorinated segment, and this could be exploited for designing functionalized surfaces with insertion of other molecules in the defect region. PMID- 26364076 TI - Inulin as a novel biocompatible coating: evaluation of surface affinities toward CaHPO4, alpha-Fe2O3, ZnO, CaHPO4@ZnO and alpha-Fe2O3@ZnO nanoparticles. AB - The introduction of biocompatible coatings onto nanoparticle surfaces can be synthetically challenging. In this work, calcium phosphate (brushite, CaHPO4?2H2O), iron oxide (hematite, alpha-Fe2O3), zinc oxide (ZnO), and CaHPO4@ZnO and alpha-Fe2O3@ZnO nanoparticles were synthesized and treated with the biocompatible, biodegradable, polysaccharide inulin {(2R,3S,4S,5R)-2 [[(2R,3S,4S,5R)-3,4-dihydroxy-2,5-bis(hydroxymethyl)oxolan-2-yl]oxymethyl]-5 (hydroxymethyl)oxolane-2,3,4-triol} under mild conditions. The products were fully characterized by Fourier transforms infrared (FTIR) spectroscopy, energy dispersive spectroscopy (EDS), dynamic light scattering (DLS), differential thermogravimetric/differential thermal analysis (TGA/DTA), transmission electron microscopy (TEM) and powder X-ray diffraction (XRD). Surface interactions among hematite and brushite with inulin are weak, but coating the nanoparticle surface with ZnO increased the affinity toward the polysaccharide. Inulin adsorption on the nanoparticle surface was confirmed by thermal and spectroscopic analyses. The nanoparticles had diameters ranging from 50 to 80nm, with nearly spherical morphology. The nanoparticles sizes, stability and solubility in water could make them useful as components for enriched foods. PMID- 26364077 TI - The challenge of a ban on animal testing for the development of a regulated legal market for new psychoactive substances (NPS) ('legal highs') in New Zealand: Issues and options for resolution. AB - BACKGROUND: In mid-July 2013, New Zealand passed the Psychoactive Substances Act (PSA), which allowed 'low risk' psychoactive products ('legal highs') to be approved for legal sale. In early May 2014, following public protest, the Psychoactive Substances Amendment Act (PSAA) was passed banning animal testing of psychoactive products, potentially making the new regime unworkable. AIM: To investigate strategies to overcome the impasse created by the animal testing ban. METHODS: Solutions to the impasse were investigated using 'scenario' and 'stakeholder' analysis. Legislation, parliamentary debates, and regulatory statements related to the PSA and animal testing were reviewed. Strategies to resolve the impasse were discussed with stakeholders including the Psychoactive Substances Regulatory Authority (PSRA) officials, health officials, a legal high industry lawyer, and a leading legal highs manufacturer. This process generated six possible scenarios and five decision-making criteria of key importance to major stakeholders. Scenarios were then evaluated based on feedback from the industry and regulators. RESULTS: The six scenarios were: (1) pragmatic modification of the animal testing ban; (2) waiting until new non-animal test models are internationally accepted; (3) use of non-validated replacement test methods; (4) judicial challenge of the animal testing ban; (5) 'creative compliance' by only presenting human clinical trial results; and (6) philosophical re-conceptualisation of the 'benefits' from psychoactive products. Options 1 and 5 appear to be the most attractive overall solutions. However, both rely on a new political consensus and astute framing of the issues by political communicators. Political decision makers may be happy to accept Scenario 2 which would impose significant delays. CONCLUSIONS: A 'failed' pharmaceutical product with psychoactive effects may have the test data required to be approved under Scenarios 1 and 5. Ultimately, the pleasurable benefits from psychoactive products may need to be included in the debate. PMID- 26364078 TI - In their own words: Content analysis of pathways to recovery among individuals with the lived experience of homelessness and alcohol use disorders. AB - BACKGROUND: Alcohol use disorders (AUDs) are more prevalent among homeless individuals than in the general population, and homeless individuals are disproportionately affected by alcohol-related morbidity and mortality. Unfortunately, abstinence-based approaches are neither desirable to nor highly effective for most members of this population. Recent research has indicated that homeless people aspire to clinically significant recovery goals beyond alcohol abstinence, including alcohol harm reduction and quality-of-life improvement. However, no research has documented this population's preferred pathways toward self-defined recovery. Considering principles of patient-centred care, a richer understanding of this population's desired pathways to recovery may help providers better engage and support them. METHODS: Participants (N=50) had lived experience of homelessness and AUDs and participated in semi-structured interviews regarding histories of homelessness, alcohol use, and abstinence-based treatment as well as suggestions for improving alcohol treatment. Conventional content analysis was used to ascertain participants' perceptions of abstinence based treatment and mutual-help modalities, while it additionally revealed alternative pathways to recovery. RESULTS: Most participants reported involvement in abstinence-based modalities for reasons other than the goal of achieving long term abstinence from alcohol (e.g., having shelter in winter months, "taking a break" from alcohol use, being among "like-minded people"). In contrast, most participants preferred alternative pathways to recovery, including fulfilling basic needs (e.g., obtaining housing), using harm reduction approaches (e.g., switching from higher to lower alcohol content beverages), engaging in meaningful activities (e.g., art, outings, spiritual/cultural activities), and making positive social connections. CONCLUSIONS: Most people with the lived experience of homelessness and AUDs we interviewed were uninterested in abstinence-based modalities as a means of attaining long-term alcohol abstinence. These individuals do, however, have creative ideas about alternative pathways to recovery that treatment providers may support to reduce alcohol-related harm and enhance quality of life. PMID- 26364079 TI - Sperm freezing to address the risk of azoospermia on the day of ICSI. AB - STUDY QUESTION: In which cases is freezing of ejaculated sperm indicated before ICSI? SUMMARY ANSWER: Sperm freezing should be performed only when out of two analyses at least one total sperm count in the ejaculate is lower than 10(6). WHAT IS KNOWN ALREADY: Due to variations in individual sperm parameters, in cases of severe oligozoospermia there is a risk of absence of spermatozoa on the day of ICSI, leading to cancellation of the attempt. Sperm freezing can avoid this problem but little is known of the parameters governing the decision to freeze sperm or not. STUDY DESIGN, SIZE, DURATION: This retrospective study included 247 men who underwent sperm cryopreservation to prevent the risk of azoospermia on the day of ICSI, from 2000 to 2012. PARTICIPANTS/MATERIALS, SETTING, METHODS: Receiver operating characteristic curve analysis was used to define the threshold value. The lowest total sperm count per ejaculate was studied as a predictive factor for the use of frozen sperm in a total of 593 ICSI attempts. Moreover, 2003 patients who had at least 4 semen analyses for andrological diagnosis have been studied to evaluate the reproducibility of sperm count. To evaluate the psychological impact of sperm freezing, a questionnaire was administered to 84 men who attended for sperm cryopreservation between June and December 2014. The cost of sperm freezing was analysed according to the French prices. MAIN RESULTS AND THE ROLE OF CHANCE: When at least one total sperm count was <10(5) the risk of azoospermia in at least one ICSI attempt was 52% (34/66) versus 3% (5/181) when all counts were >=10(5) (P < 0.0001). However, the study of the reproducibility of pre-ICSI semen analyses has shown wide variations among ejaculates, and therefore sperm freezing is recommended when one analysis from at least two, showed a sperm count <10(6). Such a policy could allow a saving of about ?70 000 by avoiding unnecessary sperm freezings. The psychological impact of sperm freezing was good since >70% of men had positive feelings about this technique. LIMITATIONS, REASONS FOR CAUTION: This was a fairly short-term study and preservation of future fertility was not assessed. It appeared impossible to find a threshold that would predict the risk of azoospermia with 100% accuracy. Therefore there is still a risk of absence of spermatozoa on the day of ICSI despite a good negative predictive value when no total sperm count was lower than 10(5). WIDER IMPLICATIONS OF THE FINDINGS: These data suggest that sperm freezing should be proposed when total sperm count is lower than 10(6) to avoid cancellation of the ICSI attempt due to azoospermia. PMID- 26364080 TI - A prospective randomized controlled trial investigating the effect of artificial shrinkage (collapse) on the implantation potential of vitrified blastocysts. AB - STUDY QUESTION: What is the effect of artificial shrinkage by laser-induced collapse before vitrification on the implantation potential after transfer of vitrified-warmed blastocysts? SUMMARY ANSWER: The artificial shrinkage by laser induced collapse did not significantly increase the implantation rate per transferred collapsed blastocyst (37.6%) compared with non-collapsed blastocysts (28.9%) [odds ratio (OR): 1.48, 95% confidence interval (CI): 0.78-2.83]. WHAT IS KNOWN ALREADY: Retrospective studies have demonstrated that artificial shrinkage of the blastocyst prior to vitrification can have a positive effect on blastocyst survival after warming. A recent study found a similar survival rate but higher implantation rate for collapsed blastocysts. So far, no randomized controlled trial has been conducted to investigate the implantation potential of collapsed blastocysts. STUDY DESIGN, SIZE, DURATION: Prospective randomized trial. Patients were recruited from December 2011 until April 2014 and warming cycles were included until July 2014. Patients were randomized in the fresh cycle if blastocysts were available for vitrification and were allocated to the study or control arm according to a computer-generated list. In the study group, blastocysts underwent laser-induced collapse before vitrification. In the control group, blastocysts were vitrified without collapsing. PARTICIPANTS/MATERIALS, SETTING, METHODS: In total, 443 patients signed informed consent and 270 patients had blastocysts vitrified. One-hundred and thirty-five patients were allocated to the study group and 135 to the control group. Sixty-nine patients from the study group and 69 from the control group returned for at least one warming cycle in which 85 and 93 blastocysts were warmed in the first cycle, respectively. Primary outcome was implantation rate per embryo transferred in the first warming cycle. Secondary outcomes were survival and transfer rates, blastocyst quality after warming, clinical pregnancy rate and implantation rate per warmed blastocyst. Blastocysts were vitrified-warmed one by one using closed vitrification and one or two blastocysts were transferred per warming cycle. MAIN RESULTS AND THE ROLE OF CHANCE: We calculated that the group sample sizes of 80 embryos in the collapse group and 80 embryos in the control group were needed to achieve 80% power to detect a difference between the group proportions of +20% with P < 0.05. In the study group, 69 first warming cycles resulted in 69 transfers with 1.2 blastocysts (n = 85) transferred. In the control group, an average of 1.3 blastocysts (n = 83) were transferred in 67 out of 69 warming cycles. Implantation rates per embryo transferred in the first warming cycle were not different between both groups (38 versus 29%, OR: 1.48; 95% CI: 0.78-2.83), neither was the implantation rate per warmed embryo (38 versus 26%, OR: 1.74; 95% CI: 0.92-3.29). When all warming cycles were considered (n = 135 in each group), survival rate after collapse was significantly higher compared with the control group (98.0 versus 92.0%, OR: 4.25; 95% CI: 1.19-15.21). Furthermore, a higher percentage of high-quality blastocysts (36.3 versus 23.5%, OR: 1.86; 95% CI: 1.12 3.08) and hatching blastocysts (19.2 versus 5.4%, OR: 4.18; 95% CI: 1.84-9.52) were found compared with the control group. LIMITATIONS, REASONS FOR CAUTION: The study lasted more than 2.5 years since fewer patients than expected returned for a warming cycle because of the high ongoing pregnancy rates in the fresh IVF/ICSI cycle. WIDER IMPLICATIONS OF THE FINDINGS: Although no significant higher implantation rate was found after collapse, the better survival and post-warm embryo quality convinced us to recognize a clinical benefit of artificial shrinkage and to implement it in routine vitrification practice. TRIAL REGISTRATION NUMBER: NCT01980225, www.clinicaltrials.gov. The first patient was included November 2011 and the study was registered October 2013. PMID- 26364081 TI - Frozen-thawed embryo transfer in a natural or mildly hormonally stimulated cycle in women with regular ovulatory cycles: a RCT. AB - STUDY QUESTION: Can ovarian stimulation with low dose hMG improve the implantation rate (IR) per frozen-thawed embryo transferred (FET) when compared with natural cycle in an FET programme in women with a regular ovulatory cycle? SUMMARY ANSWER: Both IR and live birth rate (LBR) per FET were similar in the group with mild ovarian stimulation and the natural cycle group. WHAT IS KNOWN ALREADY: Different cycle regimens for endometrial preparation are used prior to FET: spontaneous ovulatory cycles, cycles with artificial endometrial preparation using estrogen and progesterone hormones, and cycles stimulated with gonadotrophins or clomiphene citrate. At present, it is not clear which regimen results in the highest IR or LBR. More specifically, there are no RCTs in ovulatory women comparing reproductive outcome after FET during a natural cycle and during a hormonally stimulated cycle. STUDY DESIGN, SIZE, DURATION: A total of 410 women scheduled for FET during 579 cycles (December 2003-September 2013) were enrolled in an open-label RCT to natural cycle (NC FET group, n = 291) or to a cycle hormonally stimulated with s.c. gonadotrophins (hMG FET group, 37.5-75 IU per day, n = 288). A total of 672 embryos were transferred during 434 cycles (332 embryos and 213 cycles in the NC FET group; 340 embryos and 221 cycles in the hMG FET group). Assuming a = 0.05 and 80% power, it was calculated that 219 frozen thawed embryos were required for transfer in each group to demonstrate a difference of 10% in IR. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women were eligible according to the following inclusion criteria: regular ovulatory cycle, female age >=21 years and <=45 years, informed consent. FET cycles with preimplantation genetic screening were excluded. The primary outcome was IR per embryo transferred. Secondary outcomes included IR with fetal heart beat (FHB), LBR per embryo transferred and endometrial thickness on the day of hCG administration. Statistical analysis was by intention to treat and controlled for the presence of multiple measures, as eligible women could be randomized in more than one cycle. Chi-square and independent t-test were used to compare categorical and continuous variables. The relative risk (RR) was estimated using a Poisson model with log link. Hierarchical models with random intercepts for patient and cycle were considered to account for clustering of cycles within patients and of embryos within cycles. MAIN RESULTS AND THE ROLE OF CHANCE: The primary outcome, IR per embryo transferred, was not statistically different between the NC FET group (41/332 (12.35%)) and in the hMG FET group (55/340 (16.18%)) (RR 1.3 (95% confidence interval (CI) 0.9-2.0), P = 0.19). Similarly, the secondary outcome, IR with FHB per embryo transferred, was 34/332 (10.24%) in the NC FET group and 48/340 (14.12%) in the hMG FET group (RR 1.4 (95% CI 0.9 2.1), P = 0.15). The LBR per embryo transferred was 32/332 (9.64%) in the NC FET group and 45/340 (13.24%) in the hMG FET group (RR 1.4 (95% CI 0.9-2.2), P = 0.17). Endometrial thickness was also similar in both groups [8.9 (95% CI 8.7 9.1) in the NC FET group and 8.9 (95% CI 8.7-9.1) in the hMG FET group]. The duration of the follicular phase was significantly shorter (P < 0.001) in the hMG FET group [13.7 days (95% CI 13.2-14.2)] than in the NC FET group [15.4 days (95% CI 14.8-15.9)]. LIMITATIONS, REASONS FOR CAUTION: Randomization of cycles instead of patients; open-label design; relatively long period of recruitment. WIDER IMPLICATIONS OF THE FINDINGS: Our observation that the IR per embryo transferred is not significantly increased after FET during natural or gonadotrophin stimulated cycle, suggests that the effect of mild hormonal stimulation with gonadotrophins is smaller than what was considered clinically relevant with respect to reproductive outcome after FET. These data suggest that endometrial receptivity is not relevantly improved, but also not impaired after hormonal stimulation with gonadotrophins. Since FET during a natural cycle is cheaper and more patient-friendly, we recommend this regimen as the treatment of choice for women with regular cycles undergoing FET. TRIAL REGISTRATION NUMBER: clinicaltrials.gov NCT00492934. TRIAL REGISTRATION DATE: 26 June 2007. DATE OF FIRST PATIENT'S ENROLMENT: 1 December 2003. PMID- 26364082 TI - Pregnant women maintain body temperatures within safe limits during moderate intensity aqua-aerobic classes conducted in pools heated up to 33 degrees Celsius: an observational study. AB - QUESTION: What is the body temperature response of healthy pregnant women exercising at moderate intensity in an aqua-aerobics class where the water temperature is in the range of 28 to 33 degrees Celsius, as typically found in community swimming pools? DESIGN: An observational study. PARTICIPANTS: One hundred and nine women in the second and third trimester of pregnancy who were enrolled in a standardised aqua-aerobics class. OUTCOME MEASURES: Tympanic temperature was measured at rest pre-immersion (T1), after 35minutes of moderate intensity aqua-aerobic exercise (T2), after a further 10minutes of light exercise while still in the water (T3) and finally on departure from the facility (T4). The range of water temperatures in seven indoor community pools was 28.8 to 33.4 degrees Celsius. RESULTS: Body temperature increased by a mean of 0.16 degrees Celsius (SD 0.35, p<0.001) at T2, was maintained at this level at T3 and had returned to pre-immersion resting values at T4. Regression analysis demonstrated that the temperature response was not related to the water temperature (T2 r = 0.01, p = 0.9; T3 r = -0.02, p=0.9; T4 r=0.03, p=0.8). Analysis of variance demonstrated no difference in body temperature response between participants when grouped in the cooler, medium and warmer water temperatures (T2 F=0.94, p=0.40; T3 F=0.93, p=0.40; T4 F=0.70, p=0.50). CONCLUSIONS: Healthy pregnant women maintain body temperatures within safe limits during moderate-intensity aqua aerobic exercise conducted in pools heated up to 33 degrees Celsius. The study provides evidence to inform guidelines for safe water temperatures for aqua aerobic exercise during pregnancy. PMID- 26364083 TI - High-flow oxygen reduces 90-day mortality, compared with standard oxygen or non invasive ventilation, in patients with acute hypoxaemic respiratory failure [commentary]. PMID- 26364084 TI - Feedback about walking activity does not increase walking activity levels during inpatient rehabilitation after stroke [synopsis]. PMID- 26364085 TI - Very early mobilisation within 24 hours of stroke results in a less favourable outcome at 3 months [commentary 3]. PMID- 26364086 TI - Feedback about walking activity does not increase walking activity levels during inpatient rehabilitation after stroke [commentary]. PMID- 26364087 TI - Very early mobilisation within 24 hours of stroke results in a less favourable outcome at 3 months [synopsis]. PMID- 26364088 TI - Assessing baseline comparability in randomised trials. PMID- 26364089 TI - The evaluation of physical properties and in vitro cell behavior of PHB/PCL/sol gel derived silica hybrid scaffolds and PHB/PCL/fumed silica composite scaffolds. AB - PHB/PCL/sol-gel derived silica hybrid scaffolds (P5S1S) and PHB/PCL/fumed silica composite scaffolds (P5S1N) with a 5:1 organic/inorganic ratio were fabricated through a combination of electrospinning and sol-gel methods and dispersion electrospinning, respectively. In contrast to the silica nanoparticle aggregates appearing on the fiber surface of P5S1N, smooth and uniform fibers were obtained for P5S1S. The fiber diameter distribution, tensile strength, thermal gravimetric analysis (TGA), and cellular behavior of both types of scaffolds were characterized and studied. The tensile strength results and TGA indicated that the interfacial interaction between the organic and the inorganic phase was enhanced in P5S1S over the nanocomposite scaffolds, and cells exhibited significantly higher alkaline phosphate activity (ALP) for P5S1S, which makes P5S1S hybrid scaffolds candidate materials for bone tissue engineering applications. PMID- 26364090 TI - The stimuli-responsive multiphase behavior of core-shell nanogels with opposite charges and their potential application in in situ gelling system. AB - Concentrated p(N-isopropylacrylamide) (PNIPAM) nanogel dispersions exhibited rich temperature-sensitive sol-gel phase transition behavior. In the present work, the influence of electrostatic forces between nanogel particles, including attraction and repulsion, on the sol-gel phase transition behavior of PNIPAM nanogel dispersions has been studied. Both oppositely charged nanogels with core-shell structures (NIA and PND nanogels) were synthesized, and their shell charges were calculated to -0.33 and 0.082 mmol/g by potentiometric titration method. When mixed with various ratio of negative and positive charge (NC value), the resultant mixture dispersions of NIA and PND nanogel (OCNs) exhibited different aggregating behavior from NIA and PND nanogels. OCN-e aggregates (NC value=1/4), which exhibited temperature-independence of electric neutrality, had the maximum size, about 1.9-2.2 times larger than NIA or PND nanogels. Concentrated OCN-e dispersions exhibited stronger ability to form shrunken gel. Its CGC was about 2.0 wt%, 4-times lower than that of NIA and PND nanogels (about 8.0 wt%). In vitro and in vivo gelling results indicated that OCN-e aggregates could form free standing gel with good mechanical strength, and were promising to be developed as new in situ gelling system. PMID- 26364091 TI - Effect of inclusion complexation of meloxicam with beta-cyclodextrin- and beta cyclodextrin-based nanosponges on solubility, in vitro release and stability studies. AB - The objective of the present work was to develop inclusion complexes of meloxicam with beta-cyclodextrin- and beta-cyclodextrin-based nanosponges to enhance their solubility and stability and to prolong release using different methods that included physical mixing, kneading and sonication. Particle size, zeta potential, encapsulation efficiency, stability study results, in vitro and in vivo drug release study results, FTIR, DSC and XRPD were used as characterization parameters. SEM (Scanning Electron Microscope) studies revealed that the particle sizes of the inclusion complexes of meloxicam were within the range of 350 +/- 5.69-765 +/- 13.29 nm. The zeta potentials were sufficiently high to obtain stable formulations. In vitro and in vivo release studies revealed the controlled release of meloxicam from the nanosponges for 24h. The interaction of the meloxicam with the nanosponges was confirmed by FTIR and DSC. A XRPD study revealed that the crystalline nature of meloxicam was changed to an amorphous form due to the complexation with the nanosponges. A stability study revealed that the meloxicam nanosponges were stable. Therefore, beta-cyclodextrin-based nanosponges represent a novel approach for the controlled release of meloxicam for anti-inflammatory and analgesic effects. PMID- 26364093 TI - Cultural lag: A new challenge for mastitis control on dairy farms in the United States. AB - Recent changes in the US dairy industry include increases in herd size and the proportion of milk that is produced by large herds. These changes have been accompanied by an increased reliance on hired employees and an increasing role of immigrant labor to perform critical tasks such as milking cows. Thus, there is a growing need for training and education programs for dairy employees because many employees lack previous dairy experience and employee turnover rates are problematic on many farms. Although extension programs have played an important role in the education and support of dairy producers and allied professionals in attaining improved milk quality, dairy employees have limited access to educational programs. Additionally, metrics to assess employee learning are not validated and the ability to sustain work-related behavioral change has not been well described. In this article, we propose a model that may further our understanding of communication and cultural barriers between dairy managers and employees, based on a demonstration project in 12 Michigan dairy herds. As part of this demonstration, a pilot survey was tested to assess the management culture on dairy farms. Results from this survey found that only 23% of employees across all herds were able to meet with farm management on a regular basis, 36% of employees did not know somatic cell count goals for the farm for which they worked, and 71% of employees stated they primarily received training on milking protocols by other employees or that they learned on their own. Latino employees were more likely to not know farm goals or receive primary training on milking protocols from other employees or on their own compared with their English speaking counterparts. The survey information, along with input from focus group discussions with participating dairy producers, veterinarians, and employees, suggests that extension needs to build capacity for on-farm training and education for employees to support their engagement within dairy operations. PMID- 26364092 TI - Changes in milk yield, lactate dehydrogenase, milking frequency, and interquarter yield ratio persist for up to 8 weeks after antibiotic treatment of mastitis. AB - Within the dairy industry, the appearance of milk and withdrawal time due to antibiotic residuals in the milk are used to determine recovery status after cases of treated mastitis. However, both milk production and dairy cow behavior have been shown to be affected after the normalization of milk appearance, indicating that animals may not have fully recovered. The aim of the present study was to describe the changes in milk yield, lactate dehydrogenase activity, milking frequency, and interquarter yield ratio (defined as the coefficient of variation between the active quarters) after cases of naturally occurring mastitis with special focus on the recovery period after antibiotic treatment. A second aim was to examine whether these changes were affected by the pathogens present at the time of mastitis diagnosis. This retrospective study was based on a cohort data set including 1,032 lactations from 795 dairy cows kept on 2 Danish farms and milked by an automatic milking system. A total of 174 treated mastitis cases were compared with nontreated control cows from 5 wk before treatment and until 8 wk after. Treated mastitis resulted in reduced milk yield, elevated lactate dehydrogenase activity, lower milking frequency, and elevated interquarter yield ratio. Within these measures, deviations from baseline levels and from the control cows were found as early as 1 to 3 wk before the antibiotic treatment and peaked around the days of treatment. In some cases, the mastitic cows returned to premastitis levels, whereas in others they remained affected throughout the rest of the observation period. To correctly estimate the effects of treated mastitis and the recovery status of cows, it is important to take the individual cow into account and not only compare with herd levels, as this might mask the true degree of the changes. The effects on each outcome variable depended on the involved pathogen and differences were found between primiparous cows and older animals. However, in general, the changes in milk production, lactate dehydrogenase activity, and interquarter yield ratio showed parallels, suggesting that the recovery period continued for weeks after antibiotic treatment. These results call for further investigation into management of mastitic dairy cows to optimize recovery, limit milk loss, and ensure animal welfare during the period after mastitis. PMID- 26364094 TI - The effect of milking reinitiation following extended nonmilking periods on lactation in primiparous dairy cows. AB - In dairy cows, extended periods of nonmilking results in reduced milk secretion, modifications in milk composition, and eventually involution of the mammary glands. The aim of this study was to determine the effect of extended nonmilking periods on the recovery of milk yield and composition, and levels of prolactin and insulin-like growth factor-I in pasture-fed cows after resuming milking. Pasture-fed, primiparous, nonpregnant, Friesian dairy cows at mid lactation (mean +/- standard deviation, 97 +/- 2d in milk, 14.0 +/- 2.5 L/d) were divided into 3 groups (n=6 per group). The cows were subjected to nonmilking periods of 7, 14, or 28d. Twice-daily milking was resumed for 7d following the nonmilking periods. Milk yield recoveries at the end of the 7-d remilking period were 91, 51, and 29% for the 7, 14, and 28-d nonmilked groups, respectively. The somatic cell count declined to less than 400,000 cells/mL by d 3 and 6 of remilking for the 7- and 14-d-nonmilked groups, respectively, but remained greater than 800,000 cells/mL in the 28-d-nonmilked group through the 7-d remilking period. By d 7 of remilking, the somatic cell count for the 7-d-nonmilked group was not different from pretrial values. Upon remilking, the milk fat content returned to pretrial values for the 7- and 14-d-nonmilked groups, although it remained lower than pretrial for the 28-d-nonmilked group. All 3 nonmilked groups had a higher milk protein content following 7d of remilking, compared with pretrial values. The lactose content returned to pretrial values for the 7-d-nonmilked group but remained lower for the 14- and 28-d-nonmilked groups. Circulating prolactin concentrations increased once remilking was resumed, compared with the pretrial and nonmilking periods. Prolactin concentrations did not majorly differ between the groups, with the levels upon 7d of remilking remaining higher than the pretrial concentrations and the nonmilked periods. Plasma concentrations of insulin-like growth factor-I increased during the nonmilking period and were greater in all 3 nonmilked groups on d 1 of remilking than pretrial values and returned to pretrial concentrations following remilking for the 7-d-nonmilked group, whereas the 14- and 28-d-nonmilked groups remained higher than the pretrial values. These data indicate that the process of involution is fully reversed after remilking following 7d of milk stasis but more extended periods of nonmilking prevent the complete recovery of lactation. However, even after 28d of milk stasis, the milk synthesis capacity of the mammary gland could still be partially recovered. PMID- 26364095 TI - Effects of feeding birdsfoot trefoil hay on neutral detergent fiber digestion, nitrogen utilization efficiency, and lactational performance by dairy cows. AB - This experiment was conducted to determine effects of feeding birdsfoot trefoil hay-based diets in comparison with an alfalfa hay-based diet on N utilization efficiency, ruminal fermentation, and lactational performance by mid-lactation dairy cows. Nine multiparous lactating Holstein cows (131 +/- 22.6 d in milk), 3 of which were rumen fistulated, were fed 3 experimental diets in a replicated 3 * 3 Latin square design with 3 periods of 14 d of adaptation and 7 d of data and sample collection. Within squares, cows were randomly assigned to diets as follows: alfalfa hay-based diet (AHT), alfalfa and birdsfoot trefoil hay-based diet (ABT), and birdsfoot trefoil hay-based diet (BT). Intakes of dry matter and crude protein were similar across treatments, whereas ABT and BT diets resulted in decreased fiber intake compared with AHT. Feeding BT tended to increase neutral detergent fiber digestibility compared with AHT and ABT. Milk yield tended to increase for cows consuming ABT or BT diets. Milk true protein concentration and yield were greater for cows consuming ABT relative to those fed AHT. Concentration of total volatile fatty acids tended to increase by cows fed BT compared with those fed AHT and ABT. Feeding birdsfoot trefoil hay in a total mixed ration resulted in a tendency to decrease acetate proportion, but it tended to increase propionate proportion, leading to a tendency to decrease acetate-to propionate ratio. Whereas concentration of ammonia-N was similar across treatments, cows offered BT exhibited greater microbial protein yield relative to those fed AHT and ABT. Cows offered birdsfoot trefoil hay diets secreted more milk N than AHT, resulting in improved N utilization efficiency for milk N. The positive effects due to feeding birdsfoot trefoil hay were attributed to enhanced neutral detergent fiber digestion, and thus it could replace alfalfa hay in high forage dairy diets while improving N utilization efficiencies and maintaining lactational performance compared with alfalfa hay. PMID- 26364096 TI - Short communication: Quantification of carbohydrates in whey permeate products using high-performance anion-exchange chromatography with pulsed amperometric detection. AB - A method was developed for the characterization and quantification of the disaccharide lactose and 3 major bovine milk oligosaccharides (BMO) in dairy streams. Based on high-performance anion-exchange chromatography-pulsed amperometric detection (HPAE-PAD), this method is advantageous because it requires minimal sample preparation and achieves good chromatographic separation of oligosaccharide isomers within 30min. The linear dynamic range and limit of detection were 0.1 to 10mg/L and 0.03 to 0.22mg/L, respectively. Mean recoveries of the BMO were excellent and ranged from 98.4 to 100.4%. Without complicated sample preparation procedures, this HPAE-PAD method measured BMO [3' sialyllactose (3'SL), 6'-sialyllactose (6'SL), and 6'-sialyllactosamine (6'SLN)] and lactose using a single instrument, therefore increasing the accuracy of the measurement and applicability for the dairy industry. In colostrum whey permeate, 3'SL, 6'SL, and 6'SLN were 94, 29, and 46mg/L, respectively. This work is the first to demonstrate that some commercial products, currently marketed for supporting a healthy immune system, contain significant amounts of bioactive BMO and therefore, carry additional bioactivities. PMID- 26364097 TI - Short communication: Casein hydrolysate and whey proteins as excipients for cyanocobalamin to increase intestinal absorption in the lactating dairy cow. AB - Bioavailability of vitamin B12 is low in humans and animals. Improving vitamin B12 absorption is important for optimal performance in dairy cows and for increasing vitamin B12 concentrations in milk for human consumption. However, when supplemented in the diet, 80% of synthetic vitamin B12, cyanocobalamin (CN CBL), is degraded in the rumen of dairy cows and only 25% of the amount escaping destruction in the rumen disappears from the small intestine between the duodenal and ileal cannulas. In pigs, vitamin B12 from milk is more efficiently absorbed than synthetic CN-CBL. The objective of this study was to determine the efficacy of casein hydrolysate and whey proteins as excipients for CN-CBL to increase portal-drained viscera (PDV) flux of the vitamin in lactating dairy cows. Four multiparous lactating Holstein cows (237 +/- 17 DIM) equipped with a rumen cannula and catheters in the portal vein and a mesenteric artery were used in a randomized Youden square design. They were fed every 2 h to maintain steady digesta flow. On experimental days, they received a postruminal bolus of (1) CN CBL alone (0.1 g), (2) CN-CBL (0.1 g) + casein hydrolysate (10 g), or (3) CN-CBL (0.1 g) + whey proteins (10 g). Starting 30 min after the bolus, blood samples were taken simultaneously from the 2 catheters every 15 min during the first 2 h and then every 2 h until 24 h postbolus. Milk yield, DMI, and vitamin B12 portal arterial difference and PDV flux were analyzed using the MIXED procedure of SAS. Milk yield and DMI were not affected by treatments. The portal-arterial difference of vitamin B12 during the 24-h period following the bolus of vitamin was greater when the vitamin was given in solution with casein hydrolysate (2.9 +/- 4.6 pg/mL) than alone (-17.5 +/- 5.2 pg/mL) or with whey protein (-13.4 +/- 4.2 pg/mL). The treatment effects were similar for the PDV flux. The present results suggest that CN-CBL given with casein hydrolysate increases vitamin B12 absorption as compared with CN-CBL given alone. PMID- 26364098 TI - Evaluation of the epidemiological and economic consequences of control scenarios for bovine viral diarrhea virus in dairy herds. AB - Bovine viral diarrhea virus (BVDV) is an important endemic infection. However, no information was available on whether it would be economically beneficial to implement a national control program in the Netherlands. Therefore, a stochastic simulation model was developed in which control scenarios were added to compare the epidemiological and economic consequences of BVDV control in Dutch dairy herds in the next 10 yr. In the epidemiological part of the model, herds could be classified as susceptible, infectious, recovered, or vaccinated. The outputs of the epidemiological module served as input for the economic module. Net costs that could be attributed to bovine viral diarrhea consisted of production losses, costs for testing, and culling persistently infected cattle in the present voluntary Dutch BVDV control program and costs for vaccination. Four different control scenarios were simulated, involving testing and culling of persistently infected (based on serum or ear-notch testing), and monitoring BVDV statuses and vaccination and were derived from BVDV control programs that are currently executed in Europe. The costs and benefits of BVDV control in the current situation and in each of the simulated control scenarios were evaluated assuming an annual discount rate of 2%. The model estimated a mean BVDV herd prevalence of 18.0% in 2014 and showed a slightly decreasing prevalence over time. The outputs seemed realistic for the present situation in the Netherlands when compared with actual survey data. The average annual net costs associated with bovine viral diarrhea were estimated at ?27.8 million for the dairy industry. Two control scenarios were beneficial in controlling BVDV during the study period (between 2015 and 2025). In the scenario where tracing and removing of PI animals and monitoring of the subsequent status was obligatory, the benefit to cost (B/C) ratio was 1.5 (?1.5 benefit for each invested euro). In the scenario in which the BVDV status of all herds was determined, followed by voluntary measures before control measures became obligatory, the B/C ratio was 1.1. The B/C ratio of the scenarios included could be even higher when it was assumed that nondairy herds participated in the control program as well. The model provided the opportunity to compare the effect of voluntary and mandatory control scenarios on the BVDV prevalence and costs and benefits relative to the current situation in the Netherlands. The model was used to support policy makers in their decisions about a BVDV control program. PMID- 26364099 TI - Staphylococci in cattle and buffaloes with mastitis in Dakahlia Governorate, Egypt. AB - The aim of this study was to provide the first detailed insight into the population structure of Staphylococcus aureus in one modern dairy farm (Gamasa) and several household cows and buffaloes in Dakahlia Governorate, Egypt. Eight hundred seventy-two quarter milk samples of 218 dairy cattle and buffaloes with clinical and subclinical mastitis were investigated. Bacteria were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and staphylococci were further characterized by DNA sequencing of 16S rRNA genes and microarray analysis. Staphylococcus aureus was present in 5.6% of all collected samples, whereas methicillin-resistant S. aureus (MRSA) represented 24.5% of all identified S. aureus (12/49). Six clonal complexes (CC) of S. aureus were detected. Staphylococcus aureus CC398 (ST291/813)-MSSA (methicillin-susceptible S. aureus) was identified frequently in the Gamasa farm in addition to a few CC5-MRSA-V isolates. However, a small number of different isolates of S. aureus were found in household cattle and buffaloes harboring different CC. The presence of these genotypes of S. aureus in milk might indicate a public health hazard, because all of these CC have previously been isolated from human patients. Thus, a recommendation was given to the owner of the dairy farm to review the hygiene regimen on the farm. In perspective, further investigation regarding S. aureus screening of all lactating cows and personnel on the farm is warranted. PMID- 26364100 TI - Effects of soybean meal or canola meal on milk production and methane emissions in lactating dairy cows fed grass silage-based diets. AB - This study evaluated the effects of soybean meal (SBM) and heat-moisture-treated canola meal (TCM) on milk production and methane emissions in dairy cows fed grass silage-based diets. Twenty-eight Swedish Red cows were used in a cyclic change-over experiment with 4 periods of 21 d and with treatments in 2 * 4 factorial arrangement (however, the control diet without supplementary protein was not fed in replicate). The diets were fed ad libitum as a total mixed ration containing 600 g/kg of grass silage and 400 g/kg of concentrates on a dry matter (DM) basis. The concentrate without supplementary protein consisted of crimped barley and premix (312 and 88 g/kg of DM), providing 130 g of dietary crude protein (CP)/kg of DM. The other 6 concentrates were formulated to provide 170, 210, or 250 g of CP/kg of DM by replacing crimped barley with incremental amounts of SBM (50, 100, or 150 g/kg of diet DM) or TCM (70, 140, or 210 g/kg of diet DM). Feed intake was not influenced by dietary CP concentration, but tended to be greater in cows fed TCM diets compared with SBM diets. Milk and milk protein yield increased linearly with dietary CP concentration, with greater responses in cows fed TCM diets compared with SBM diets. Apparent N efficiency (milk N/N intake) decreased linearly with increasing dietary CP concentration and was lower for cows fed SBM diets than cows fed TCM diets. Milk urea concentration increased linearly with increased dietary CP concentration, with greater effects in cows fed SBM diets than in cows fed TCM diets. Plasma concentrations of total AA and essential AA increased with increasing dietary CP concentration, but no differences were observed between the 2 protein sources. Plasma concentrations of Lys, Met, and His were similar for both dietary protein sources. Total methane emissions were not influenced by diet, but emissions per kilogram of DM intake decreased quadratically, with the lowest value observed in cows fed intermediate levels of protein supplementation. Methane emissions per kilogram of energy corrected milk decreased more when dietary CP concentration increased in TCM diets compared with SBM diets. Overall, replacing SBM with TCM in total mixed rations based on grass silage had beneficial effects on milk production, N efficiency, and methane emissions across a wide range of dietary CP concentrations. PMID- 26364101 TI - Alternative strategies for genetic analyses of milk flow in dairy cattle. AB - Measurements for average milk flow (AMF) in kilograms of milk per minute of milking time from 629,161 Holstein cows from calving years 1990 to 2008 were used to estimate genetic covariance components using a variety of statistical models. For bivariate linear-threshold model applications, Gaussian-distributed AMF (linear sire model) was categorized into 2 distinct classes (threshold sire model) by setting arbitrary thresholds for extremely slow or extremely fast milking cows. In different bivariate runs with the 2 traits, Gaussian AMF and binary AMF, within a Bayesian framework, thresholds for the binary trait were 1.2, 1.6, 2.6, and 2.8 kg/min. Posterior heritabilities for AMF from the linear and the threshold models in all runs were in a narrow range and close to 0.26, and the posterior genetic correlation between AMF, defined as either a Gaussian or binary trait, was 0.99. A data subset was used to infer genetic and phenotypic relationships between AMF with test-day traits milk yield, fat percentage, protein percentage, somatic cell score (SCS), fat-to-protein ratio, and energy corrected milk using recursive linear sire models, standard multiple trait linear sire models, and multiple trait linear sire models accounting for the effect of a trait 1 on a trait 2, and of trait 2 on trait 3, via linear regressions. The time lagged 3-trait system focused on the first test-day trait after calving (trait 1), on AMF (trait 2), and on the test-day trait (trait 3) after the AMF measurement. Posterior means for heritabilities for AMF from linear and recursive linear models used for the reduced data set ranged between 0.29 and 0.38, and were slightly higher than heritabilities from the threshold models applied to the full data set. Genetic correlations from the recursive linear model and the linear model were similar for identical trait combinations including AMF and test day traits 1 and 3. The largest difference was found for the genetic correlation between AMF and fat percentage from the first test day (i.e., -0.31 from the recursive linear model vs. -0.26 from the linear model). Genetic correlations from the linear model, including an additional regression coefficient, partly differed, especially when comparing correlations between AMF and SCS and between AMF and fat-to-protein ratio recorded after the AMF measurement data. Structural equation coefficients from the recursive linear model and corresponding regression coefficients from the linear model with additional regression, both depicting associations on the phenotypic scale, were quite similar. From a physiological perspective, all models confirmed the antagonistic relationship between SCS with AMF on genetic and phenotypic scales. A pronounced recursive relationship was also noted between productivity (milk yield and energy-corrected milk) and AMF, suggesting further research using physiological parameters as indicators for cow stress response (e.g., level of hormones) should be conducted. PMID- 26364102 TI - Short communication: Substituting dry distillers grains with solubles and rumen protected amino acids for soybean meal in late-lactation cows' diets based on corn silage or ryegrass silage. AB - Excess protein in dairy cattle diets increases production costs and contributes to environmental pollution. The objective of the present study was to evaluate the effect of feeding dry distillers grains with solubles (DDGS) supplemented with rumen-protected Lys and Met in place of solvent-extracted soybean meal on the performance of late-lactation cows. Two experiments were carried out, with each using 24 late-lactating dairy cows distributed among 4 pens. In trial 1, corn silage was the main forage source. Control (HP1) total mixed ration (TMR) contained 16.3% crude protein (CP) with soybean meal as the main protein source. Treatment TMR (LP1) had 13.7% CP when soybean meal was replaced with DDGS and rumen-protected Lys and Met. Forage in trial 2 was ryegrass silage; control TMR (HP2; 15.4% CP) contained soybean meal and rumen-protected Met, whereas treatment TMR (LP2; 13.8% CP) contained DDGS and rumen-protected Lys and Met. Trials were analyzed as crossover design using the MIXED procedure of SAS (SAS Institute Inc., Cary NC) with cow as sampling unit and pen as the experimental unit. Treatments were similar in dry matter intake (21.0 and 20.4 kg/cow per day for HP1 and LP1, respectively) and milk yield (20.7 and 20.5 kg/cow per day for HP1 and LP1, respectively) during trial 1. Milk composition was similar between treatments, averaging 4.22, 3.73, 4.54, and 9.15, respectively, for fat, protein, lactose, and solids nonfat. Milk urea nitrogen decreased from 17.2 mg/dL for HP1 to 9.93 mg/dL for LP1. In trial 2, no significant differences were observed for dry matter intake (21.4 and 20.9 kg/cow per day for HP2 and LP2, respectively), milk yield (28.1 and 26.6 kg/d for HP2 and LP2, respectively), fat yield (0.99 vs. 0.92 kg/d for HP2 and LP2, respectively), protein yield (0.94 vs. 0.86 kg/d for HP2 and LP2, respectively) and lactose yield (1.37 vs. 1.28 for HP2 and LP2, respectively). Milk urea nitrogen decreased from 9.88 mg/dL with HP2 to 6.39 mg/dL with the LP2 treatment. Milk N efficiency tended to be higher for LP treatments in trial 1, but not in trial 2. Low milk urea N suggested nitrogen losses to the environment may be lower when cows were fed diets based on DDGS in both trials. The studies indicated that DDGS with rumen-protected Lys and Met could substitute solvent-extracted soybean meal in low-protein corn silage- and ryegrass silage-based diets for late-lactation dairy cows averaging 20.6 or 27.4 kg of milk/d, respectively. PMID- 26364103 TI - Release of angiotensin converting enzyme-inhibitor peptides during in vitro gastrointestinal digestion of Parmigiano Reggiano PDO cheese and their absorption through an in vitro model of intestinal epithelium. AB - The occurrence of 8 bovine casein-derived peptides (VPP, IPP, RYLGY, RYLG, AYFYPEL, AYFYPE, LHLPLP, and HLPLP) reported as angiotensin converting enzyme inhibitors (ACE-I) was investigated in the 3-kDa ultrafiltered water-soluble extract (WSE) of Parmigiano Reggiano (PR) cheese samples by ultra-performance liquid chromatography coupled to high-resolution mass spectrometry via an electrospray ionization source. Only VPP, IPP, LHLPLP, and HLPLP were revealed in the WSE, and their total amount was in the range of 8.46 to 21.55 mg/kg of cheese. Following in vitro static gastrointestinal digestion, the same ACE-I peptides along with the newly formed AYFYPEL and AYFYPE were found in the 3 kDa WSE of PR digestates. Digestates presented high amounts (1,880-3,053 mg/kg) of LHLPLP, whereas the remaining peptides accounted for 69.24 to 82.82 mg/kg. The half-maximal inhibitory concentration (IC50) values decreased from 7.92 +/- 2.08 in undigested cheese to 3.20 +/- 1.69 after in vitro gastrointestinal digestion. The 3-kDa WSE of digested cheeses were used to study the transport of the 8 ACE-I peptides across the monolayers of the Caco-2 cell culture grown on a semipermeable membrane of the transwells. After 1h of incubation, 649.20 +/- 148.85 mg/kg of LHLPLP remained in the apical compartment, whereas VPP, IPP, AYFYPEL, AYFYPE, and HLPLP accounted in total for less than 36.78 mg/kg. On average, 0.6% of LHLPLP initially present in the digestates added to the apical compartment were transported intact to the basolateral chamber after the same incubation time. Higher transport rate (2.9%) was ascertained for the peptide HLPLP. No other intact ACE-I peptides were revealed in the basolateral compartment. For the first time, these results demonstrated that the ACE-I peptides HLPLP and LHLPLP present in the in vitro digestates of PR cheese are partially absorbed through an in vitro model of human intestinal epithelium. PMID- 26364104 TI - Evaluation of performance of bacterial culture of feces and serum ELISA across stages of Johne's disease in cattle using a Bayesian latent class model. AB - The objective of this study was to evaluate the performance of bacterial culture of feces and serum ELISA to correctly identify cows with Mycobacterium avium ssp. paratuberculosis (MAP) at heavy, light, and non-fecal-shedding levels. A total of 29,785 parallel test results from bacterial culture of feces and serum ELISA were collected from 17 dairy herds in Minnesota, Pennsylvania, and Colorado. Samples were obtained from adult cows from dairy herds enrolled for up to 10 yr in the National Johne's Disease Demonstration Herd Project. A Bayesian latent class model was fitted to estimate the probabilities that bacterial culture of feces (using 72-h sedimentation or 30-min centrifugation methods) and serum ELISA results correctly identified cows as high positive, low positive, or negative given that cows were heavy, light, and non-shedders, respectively. The model assumed that no gold standard test was available and conditional independency existed between diagnostic tests. The estimated conditional probabilities that bacterial culture of feces correctly identified heavy shedders, light shedders, and non-shedders were 70.9, 32.0, and 98.5%, respectively. The same values for the serum ELISA were 60.6, 18.7, and 99.5%, respectively. Differences in diagnostic test performance were observed among states. These results improve the interpretation of results from bacterial culture of feces and serum ELISA for detection of MAP and MAP antibody (respectively), which can support on-farm infection control decisions and can be used to evaluate disease-testing strategies, taking into account the accuracy of these tests. PMID- 26364105 TI - Does animal welfare influence dairy farm efficiency? A two-stage approach. AB - This article investigated how process-based animal welfare indicators (PAI) affected the technical efficiency of German dairy farms. A sample of 115 North Rhine Westphalian dairy farms was used to estimate their technical efficiency with data envelopment analysis. A censored regression model was then applied to quantify the effects of PAI on technical efficiency. The results indicated that in particular a higher percentage of cow losses, a higher replacement rate, and a longer calving interval had, at their respective mean, a negative marginal effect on the technical efficiency of the sample farms. In contrast, a lower age of first calving, a higher in-milk performance, and a higher somatic cell count were positively correlated with technical efficiency. Some of the PAI followed a polynomial trend (i.e., their influence on technical efficiency did not have a constant sign, and levels for minimum/maximum technical efficiency were present). The minimum efficiency score at constant returns to scale was obtained when farmers had cow losses of 0.4%, a calving interval of 430d, and a cell count of 146,000 per milliliter. However, maximum technical efficiency was obtained at a milk yield of 9,796 kg per cow and year. The corresponding amounts in case of technical efficiency under variable returns to scale were at a similar level, except that milk yield showed a positive linear influence on technical efficiency. Moreover, technical efficiency under variable returns to scale was positively correlated with the fat content of milk. The lowest level of technical efficiency was reached at a fat content of 4.1%. Subsequently, we found that efficient dairy farms did not always correspond with recommended values concerning animal welfare criteria. Finally, the results showed that the assumption of a monotone effect direction of PAI on farm efficiency was inappropriate, and that this issue would need to be addressed in future research. PMID- 26364106 TI - Study of proteolysis in river buffalo mozzarella cheese using a proteomics approach. AB - The guarantee of the origin and quality of raw material is essential for the protection and valorization of Campana buffalo mozzarella cheese. The risk of utilization of semifinished products and stored milk in substitution for fresh milk is increasing, due to the continuous desire to reduce production costs. A proteomics approach and electrophoresis survey of retail mozzarella cheeses indicated different rates of proteolysis in the production of dairy industries. The use of fresh milk and correct cheesemaking protocol yielded only gamma caseins, which are derived from beta-casein by plasmin, and para-kappa-casein, which is derived from kappa-casein by chymosin. The detection of abnormal hydrolysis resulting in beta- and alphaS1-casein fragments, identified by mass spectrometry, indicates the use of stored milk or stored and pressed curd, or the reuse of unsold mozzarella cheese, to produce mozzarella. The formation of gamma caseins and other fragments during a long storage of raw materials at room or refrigeration temperature was ascribed to plasmin (endogenous milk enzyme), whereas formation of alphaS1-casein fragments, mainly alphaS1-I(6P)- and alphaS1 I(7P)-casein during the storage of curd was ascribed to the action of chymosin (exogenous enzyme) from rennet. Sodium dodecyl sulfate-PAGE and alkaline urea PAGE permitted us to evaluate the freshness of the raw materials used in the manufacturing of buffalo mozzarella cheese and to reveal possible inappropriate preservation. PMID- 26364107 TI - Susceptibility of whey protein isolate to oxidation and changes in physicochemical, structural, and digestibility characteristics. AB - Oxidation is an important factor for denaturing of whey protein isolate (WPI) during food processing. We studied the effects of chemical oxidation on physicochemical and structural changes along with in vitro digestibility of WPI in this work. Evaluation of physicochemical changes showed that carbonyl level and dityrosine content increased, whereas total and free thiol group levels decreased for oxidized WPI samples. For the structural changes, protein aggregation was measured by surface hydrophobicity, turbidity, and particle diameter, which was increased for oxidized WPI samples. The increase of the secondary structure beta-sheets and antiparallel beta-sheet also supported the aggregation of oxidized WPI. A direct quantitative relationship between physicochemical and structural changes and protein digestibility indicated that oxidation-related damage restricts the susceptibility of WPI to proteases. In conclusion, WPI had high susceptibility to oxidative stress, and both physicochemical and structural changes caused by severe oxidative stress could decrease the rate of in vitro digestibility of WPI. PMID- 26364108 TI - Joint genome-wide association study for milk fatty acid traits in Chinese and Danish Holstein populations. AB - The identification of causal genes or genomic regions associated with fatty acids (FA) will enhance our understanding of the pathways underlying FA synthesis and provide opportunities for changing milk fat composition through a genetic approach. The linkage disequilibrium between adjacent markers is highly consistent between the Chinese and Danish Holstein populations, such that a joint genome-wide association study (GWAS) can be performed. In this study, a joint GWAS was performed for 16 milk FA traits based on data of 784 Chinese and 371 Danish Holstein cows genotyped by a high-density bovine single nucleotide polymorphism (SNP) array. A total of 486,464 SNP markers on 29 bovine autosomes were used. Bonferroni corrections were applied to adjust the significance thresholds for multiple testing at the genome- and chromosome-wide levels. According to the analysis of either the Chinese or Danish data individually, the total numbers of overlapping SNP that were significant at the chromosome level were 94 for C14:1, 208 for the C14 index, and 1 for C18:0. Joint analysis using the combined data of the 2 populations detected greater numbers of significant SNP compared with either of the individual populations alone for 7 and 10 traits at the genome- and chromosome-wide significance levels, respectively. Greater numbers of significant SNP were detected for C18:0 and the C18 index in the Chinese population compared with the joint analysis. Sixty-five significant SNP across all traits had significantly different effects in the 2 populations. Ten FA were influenced by a quantitative trait loci (QTL) region including DGAT1. Both C14:1 and the C14 index were influenced by a QTL region including SCD1 in the combined population. Other QTL regions also showed significant associations with the studied FA. A large region (14.9-24.9 Mbp) in BTA26 significantly influenced C14:1 and the C14 index in both populations, mostly likely due to the SNP in SCD1. A QTL region (69.97-73.69 Mbp) on BTA9 showed a significantly different effect on C18:0 between the 2 populations. Detection of these important SNP and the corresponding QTL regions will be helpful for follow-up studies to identify causal mutations and their interaction with environments for milk FA in dairy cattle. PMID- 26364109 TI - Growth and gas formation by Lactobacillus wasatchensis, a novel obligatory heterofermentative nonstarter lactic acid bacterium, in Cheddar-style cheese made using a Streptococcus thermophilus starter. AB - A novel slow-growing, obligatory heterofermentative, nonstarter lactic acid bacterium (NSLAB), Lactobacillus wasatchensis WDC04, was studied for growth and gas production in Cheddar-style cheese made using Streptococcus thermophilus as the starter culture. Cheesemaking trials were conducted using S. thermophilus alone or in combination with Lb. wasatchensis deliberately added to cheese milk at a level of ~10(4) cfu/mL. Resulting cheeses were ripened at 6 or 12 degrees C. At d 1, starter streptococcal numbers were similar in both cheeses (~10(9) cfu/g) and fast-growing NSLAB lactobacilli counts were below detectable levels (<10(2) cfu/g). As expected, Lactobacillus wasatchensis counts were 3*10(5) cfu/g in cheeses inoculated with this bacterium and below enumeration limits in the control cheese. Starter streptococci decreased over time at both storage temperatures but declined more rapidly at 12 degrees C, especially in cheese also containing Lb. wasatchensis. Populations of fast-growing NSLAB and the slow growing Lb. wasatchensis reached 5*10(7) and 2*10(8) cfu/g, respectively, after 16 wk of storage at 12 degrees C. Growth of NSLAB coincided with a reduction in galactose concentration in the cheese from 0.6 to 0.1%. Levels of galactose at 6 degrees C had similar decrease. Gas formation and textural defects were only observed in cheese with added Lb. wasatchensis ripened at 12 degrees C. Use of S. thermophilus as starter culture resulted in galactose accumulation that Lb. wasatchensis can use to produce CO2, which contributes to late gas blowing in Cheddar-style cheeses, especially when the cheese is ripened at elevated temperature. PMID- 26364110 TI - Short communication: Genetic study of methane production predicted from milk fat composition in dairy cows. AB - Dairy cows produce enteric methane, a greenhouse gas with 25 times the global warming potential of CO2. Breeding could make a permanent, cumulative, and long term contribution to methane reduction. Due to a lack of accurate, repeatable, individual methane measurements needed for breeding, indicators of methane production based on milk fatty acids have been proposed. The aim of the present study was to quantify the genetic variation for predicted methane yields. The milk fat composition of 1,905 first-lactation Dutch Holstein-Friesian cows was used to investigate 3 different predicted methane yields (g/kg of DMI): Methane1, Methane2, and Methane3. Methane1 was based on the milk fat proportions of C17:0anteiso, C18:1 rans-10+11, C18:1 cis-11, and C18:1 cis-13 (R(2)=0.73). Methane2 was based on C4:0, C18:0, C18:1 trans-10+11, and C18:1 cis-11 (R(2)=0.70). Methane3 was based on C4:0, C6:0, and C18:1 trans-10+11 (R(2)=0.63). Predicted methane yields were demonstrated to be heritable traits, with heritabilities between 0.12 and 0.44. Breeding can, thus, be used to decrease methane production predicted based on milk fatty acids. PMID- 26364111 TI - Short communication: Determination of the ability of Thymox to kill or inhibit various species of microorganisms associated with infectious causes of bovine lameness in vitro. AB - Infectious claw diseases continue to plague cattle in intensively managed husbandry systems. Poor foot hygiene and constant moist environments lead to the infection and spread of diseases such as digital dermatitis (hairy heel warts), interdigital dermatitis, and interdigital phlegmon (foot rot). Currently, copper sulfate and formalin are the most widely used disinfecting agents in bovine footbaths; however, the industry could benefit from more environmentally and worker friendly substitutes. This study determined the in vitro minimum inhibitory concentrations and minimum bactericidal concentrations of Thymox (Laboratoire M2, Sherbrooke, Quebec, Canada) for a selection of microorganisms related to infectious bovine foot diseases. Thymox is a broad-spectrum agricultural disinfectant that is nontoxic, noncorrosive, and readily biodegradable. The values for minimum inhibitory concentration and minimum bactericidal concentration indicated that Thymox inhibited growth and killed the various species of microorganisms under study at much lower concentrations compared with the recommended working concentration of a 1% solution. Overall, the values found in this study of minimum inhibitory concentration and minimum bactericidal concentration of Thymox show its potential as an alternative antibacterial agent used in bovine footbaths; however, field trials are needed to determine its effectiveness for the control and prevention of infectious claw diseases. PMID- 26364112 TI - Short communication: Reference limits for blood analytes in Holstein late pregnant heifers and dry cows: Effects of parity, days relative to calving, and season. AB - Reference limits for metabolic profiles in Holstein late-pregnant heifers and dry cows were determined considering the effects of parity, days relative to calving, and season. Blood samples were collected from 104 pregnant heifers and 186 dry cows (68 primiparous and 118 pluriparous) from 60 to 10 d before the expected calving date in 31 dairy farms in northeastern Italy. Sampling was performed during summer (182 samples) and the following winter (108 samples). All the animals were judged as clinically healthy at a veterinary visit before sampling. Outliers were removed from data of each blood analyte, and variables that were not normally distributed were log transformed. A mixed model was used to test the fixed effects of parity (late-pregnant heifers, primiparous or pluriparous dry cows), class of days relative to calving (60-41 d, 40-21 d, 20-10 d), season (summer or winter), and the interactions between parity and class of days relative to calving and between parity and season, with farm as random effect. Single general reference limits and 95% confidence intervals were generated for analytes that did not vary according to fixed effects. Whenever a fixed effect included in the model significantly affected a given analyte, specific reference limits and 95% confidence intervals were generated for each of its levels. Albumin, urea, triglycerides, alanine aminotransferase, aspartate aminotransferase, creatinine kinase, conjugated bilirubin, calcium, phosphorus, magnesium, potassium, chloride, zinc, copper, and iron concentrations were not influenced by any of the fixed effects. Total protein, globulins, creatinine, glucose, alkaline phosphatase, gamma glutamyltransferase, lactate dehydrogenase, and sodium plasma concentrations were affected by parity. The class of days relative to calving had a significant effect on the concentrations of total protein, globulins, fatty acids, cholesterol, total bilirubin, and sodium. Season affected plasma concentrations of creatinine, glucose, fatty acids, lactate dehydrogenase, and sodium. Interactions between parity and class of days relative to calving and between parity and season did not significantly affect any of the blood analytes tested. The reference limits and the 95% confidence intervals for blood analytes determined in the study could help dairy practitioners to improve the accuracy of metabolic profile interpretation in Holstein late-pregnant cattle. PMID- 26364113 TI - Investigating the genetic background of bovine digital dermatitis using improved definitions of clinical status. AB - Bovine digital dermatitis (DD) is an increasing claw health problem in all cattle production systems worldwide. The objective of this study was to evaluate the use of an improved scoring of the clinical status for DD via M-scores accounting for the dynamics of the disease; that is, the transitions from one stage to another. The newly defined traits were then subjected to a genetic analysis to determine the genetic background for susceptibility to DD. Data consisted of 6,444 clinical observations from 729 Holstein heifers in a commercial dairy herd, collected applying the M-score system. The M-score system is a classification scheme for stages of DD that allows a macroscopic scoring based on clinical inspections of the bovine foot, thus it describes the stages of lesion development. The M-scores were used to define new DD trait definitions with different complexities. Linear mixed models and logistic models were used to identify fixed environmental effects and to estimate variance components. In total, 68% of all observations showed no DD status, whereas 11% were scored as infectious for and affected by DD, and 21% of all observations exhibited an affected but noninfectious status. For all traits, the probability of occurrence and clinical status were associated with age at observation and period of observation. Risk of becoming infected increased with age, and month of observation significantly affected all traits. Identification of the optimal month concerning DD herd status was consistent for all trait definitions; the last month of the trial was identified. In contrast, months exhibiting the highest least squares means of transformed scores differed depending on trait definition. In this respect, traits that can distinguish between healthy, infectious, and noninfectious stages of DD can account for the infectious potential of the herd and can serve as an alert tool. Estimates of heritabilities of traits studied ranged between 0.19 (+/-0.11) and 0.52 (+/ 0.17), revealing a tendency for higher values for more complex trait definitions. In terms of genetic selection, all trait definitions identified the best (i.e., most resistant) animals, but only the new trait definitions were able to distinguish between animals with average and high predispositions for DD. Considering repeated measurements resulted in heritability estimates ranging between 0.13 (+/-0.05) and 0.29 (+/-0.10). PMID- 26364114 TI - Short communication: Potential of Fresco-style cheese whey as a source of protein fractions with antioxidant and angiotensin-I-converting enzyme inhibitory activities. AB - Recently, traditional Mexican Fresco-style cheese production has been increasing, and the volume of cheese whey generated represents a problem. In this study, we investigated the chemical composition of Fresco-style cheese wheys and their potential as a source of protein fractions with antioxidant and angiotensin-I converting enzyme (ACE)-inhibitory activities. Three samples from Fresco, Panela, and Ranchero cheeses whey were physicochemically characterized. Water-soluble extracts were fractionated to obtain whey fractions with different molecular weights: 10-5, 5-3, 3-1 and <1 kDa. The results indicated differences in the lactose, protein, ash, and dry matter contents (% wt/wt) in the different Fresco style cheese wheys. All whey fractions had antioxidant and ACE-inhibitory activities. The 10-5 kDa whey fraction of Ranchero cheese had the highest Trolox equivalent antioxidant capacity (0.62 +/- 0.00 mM), and the 3-1 kDa Panela and Fresco cheese whey fractions showed the highest ACE-inhibitory activity (0.57 +/- 0.02 and 0.59 +/- 0.04 MUg/mL 50%-inhibitory concentration values, respectively). These results suggest that Fresco-style cheese wheys may be a source of protein fractions with bioactivity, and thus could be useful ingredients in the manufacture of functional foods with increased nutritional value. PMID- 26364115 TI - Effect of temperature and concentration on benzoyl peroxide bleaching efficacy and benzoic acid levels in whey protein concentrate. AB - Much of the fluid whey produced in the United States is a by-product of Cheddar cheese manufacture and must be bleached. Benzoyl peroxide (BP) is currently 1 of only 2 legal chemical bleaching agents for fluid whey in the United States, but benzoic acid is an unavoidable by-product of BP bleaching. Benzoyl peroxide is typically a powder, but new liquid BP dispersions are available. A greater understanding of the bleaching characteristics of BP is necessary. The objective of the study was to compare norbixin destruction, residual benzoic acid, and flavor differences between liquid whey and 80% whey protein concentrates (WPC80) bleached at different temperatures with 2 different benzoyl peroxides (soluble and insoluble). Two experiments were conducted in this study. For experiment 1, 3 factors (temperature, bleach type, bleach concentration) were evaluated for norbixin destruction using a response surface model-central composite design in liquid whey. For experiment 2, norbixin concentration, residual benzoic acid, and flavor differences were explored in WPC80 from whey bleached by the 2 commercially available BP (soluble and insoluble) at 5 mg/kg. In liquid whey, soluble BP bleached more norbixin than insoluble BP, especially at lower concentrations (5 and 10 mg/kg) at both cold (4 degrees C) and hot (50 degrees C) temperatures. The WPC80 from liquid whey bleached with BP at 50 degrees C had lower norbixin concentration, benzoic acid levels, cardboard flavor, and aldehyde levels than WPC80 from liquid whey bleached with BP at 4 degrees C. Regardless of temperature, soluble BP destroyed more norbixin at lower concentrations than insoluble BP. The WPC80 from soluble-BP-bleached wheys had lower cardboard flavor and lower aldehyde levels than WPC80 from insoluble-BP-bleached whey. This study suggests that new, soluble (liquid) BP can be used at lower concentrations than insoluble BP to achieve equivalent bleaching and that less residual benzoic acid remains in WPC80 powder from liquid whey bleached hot (50 degrees C) than cold (4 degrees C), which may provide opportunities to reduce benzoic acid residues in dried whey ingredients, expanding their marketability. PMID- 26364116 TI - Effects of forage source and extruded linseed supplementation on methane emissions from growing dairy cattle of differing body weights. AB - Changes in diet carbohydrate amount and type (i.e., starch vs. fiber) and dietary oil supplements can affect ruminant methane emissions. Our objectives were to measure methane emissions, whole-tract digestibility, and energy and nitrogen utilization from growing dairy cattle at 2 body weight (BW) ranges, fed diets containing either high maize silage (MS) or high grass silage (GS), without or with supplemental oil from extruded linseed (ELS). Four Holstein-Friesian heifers aged 13 mo (BW range from start to finish of 382 to 526 kg) were used in experiment 1, whereas 4 lighter heifers aged 12 mo (BW range from start to finish of 292 to 419 kg) were used in experiment 2. Diets were fed as total mixed rations with forage dry matter (DM) containing high MS or high GS and concentrates in proportions (forage:concentrate, DM basis) of either 75:25 (experiment 1) or 60:40 (experiment 2), respectively. Diets were supplemented without or with ELS (Lintec, BOCM Pauls Ltd., Wherstead, UK; 260 g of oil/kg of DM) at 6% of ration DM. Each experiment was a 4 * 4 Latin square design with 33-d periods, with measurements during d 29 to 33 while animals were housed in respiration chambers. Heifers fed MS at a heavier BW (experiment 1) emitted 20% less methane per unit of DM intake (yield) compared with GS (21.4 vs. 26.6, respectively). However, when repeated with heifers of a lower BW (experiment 2), methane yield did not differ between the 2 diets (26.6g/kg of DM intake). Differences in heifer BW had no overall effect on methane emissions, except when expressed as grams per kilogram of digestible organic matter (OMD) intake (32.4 vs. 36.6, heavy vs. light heifers). Heavier heifers fed MS in experiment 1 had a greater DM intake (9.4kg/d) and lower OMD (755 g/kg), but no difference in N utilization (31% of N intake) compared with heifers fed GS (7.9 kg/d and 799 g/kg, respectively). Tissue energy retention was nearly double for heifers fed MS compared with GS in experiment 1 (15 vs. 8% of energy intake, respectively). Heifers fed MS in experiment 2 had similar DM intake (7.2 kg/d) and retention of energy (5% of intake energy) and N (28% of N intake), compared with GS-fed heifers, but OMD was lower (741 vs. 765 g/kg, respectively). No effect of ELS was noted on any of the variables measured, irrespective of animal BW, and this was likely due to the relatively low amount of supplemental oil provided. Differences in heifer BW did not markedly influence dietary effects on methane emissions. Differences in methane yield were attributable to differences in dietary starch and fiber composition associated with forage type and source. PMID- 26364119 TI - Current Status of Proteomic Studies on Defense Responses in Rice. AB - Biotic stresses are constraints to plant growth and development negatively impacting crop production. To counter such stresses, plants have developed stress specific adaptations as well as simultaneous responses. The efficacy and magnitude of inducible adaptive responses are dependent on activation of signaling pathways and intracellular networks by modulating expression, or abundance, and/or post-translational modification of proteins associated with defense mechanisms. Proteomics plays an important role in elucidating plant defense mechanisms by mining the differential regulation of proteins to various biotic stresses. Rice, one of the most widely cultivated food crops in world, is constantly challenged by a variety of biotic stresses, and high-throughput proteomics approaches have been employed to unravel the molecular mechanism of the biotic stresses-response in rice. In this review, we summarize the latest advances of proteomic studies on defense responses and discuss the potential relevance of the proteins identified by proteomic means in rice defense mechanism. Furthermore, we provide perspective for proteomics in unraveling the molecular mechanism of rice immunity. PMID- 26364117 TI - An Overview of Proteomics Tools for Understanding Plant Defense Against Pathogens. AB - Plant diseases are responsible for important losses in crops and cause serious impacts in agricultural production. In the last years, proteomics has been used to examine plant defense responses against pathogens. Such studies may be pioneer in the generation of crops with enhanced resistance. In this review, we focus on proteomics advances in the understanding of host and non-host resistance against pathogens. PMID- 26364120 TI - [Candidemia subsequent to Clostridium difficile infection: direct relationship or coincidence?]. PMID- 26364121 TI - Assessing different measures of population-level vaccine protection using a case control study. AB - BACKGROUND: Case-control studies have not been examined for their utility in assessing population-level vaccine protection in individually randomized trials. METHODS: We used the data of a randomized, placebo-controlled trial of a cholera vaccine to compare the results of case-control analyses with those of cohort analyses. Cases of cholera were selected from the trial population followed for three years following dosing. For each case, we selected 4 age-matched controls who had not developed cholera. For each case and control, GIS was used to calculate vaccine coverage of individuals in a surrounding "virtual" cluster. Specific selection strategies were used to evaluate the vaccine protective effects. RESULTS: 66,900 out of 108,389 individuals received two doses of the assigned regimen. For direct protection among subjects in low vaccine coverage clusters, we observed 78% (95% CI: 47-91%) protection in a cohort analysis and 84% (95% CI: 60-94%) in case-control analysis after adjusting for confounding factors. Using our GIS-based approach, estimated indirect protection was 52% (95% CI: 10-74%) in cohort and 76% (95% CI: 47-89%) in case control analysis. Estimates of total and overall effectiveness were similar for cohort and case control analyses. CONCLUSION: The findings show that case-control analyses of individually randomized vaccine trials may be used to evaluate direct as well as population-level vaccine protection. PMID- 26364122 TI - Development of a novel protein biochip enabling validation of immunological assays and detection of serum IgG and IgM antibodies against Treponema pallidum pathogens in the patients with syphilis. AB - In this study, we developed a novel protein biochip methodology that was characterized by dithiobis (succinimidyl undecanoate) (DSU) and specialized for detection of serum IgG and IgM antibodies against Treponema pallidum pathogens in the patients with syphilis, respectively. The biochips were validated by a dimension of atomic force microscope (AFM). The visualized detection limit of IgG antibody on the biochip was 0.39MUg/ml. Finally, 286 serum samples from the patients with syphilis were simultaneously tested on the rTpN15-17-47 coated biochips. The results were evaluated in comparison with the assays of T. pallidum particle agglutination (TPPA) and the toluidine red unheated serum test (TRUST). The result demonstrated that the relative positive rate in the 286 patients by biochip was 99.0%, similar to that by TPPA (97.9%, P>0.05) and higher than that by TRUST, (76.2%, P<0.01). The detection specificities were 100% for the biochip and the TPPA and 97.0% for the TRUST. Thus, the protein biochip would provide a useful platform not only for enabling concurrent detection of the infectious antibodies directed against T. pallidum on a larger scale, but also for monitoring therapy modality of the disease. PMID- 26364123 TI - Inadvertent overinfusion of norepinephrine using infusion pump loading dose. AB - Programming infusion pumps has been recognised as a high-risk step and a source of adverse events (Nuckols et al., 2008; Hyman, 2010). Literature describing infusion pump loading dose errors and NORepinephrine complications is scarce (Girard et al., 2010). This case study presents the first ever report of an inadvertent overinfusion of NORepinephrine due to the loading dose option on the infusion pump, and resulting cardiac arrest of the patient. A patient was admitted to the emergency room and started on a NORepinephrine infusion inadvertently as a loading dose rather than a primary infusion. Historical values for the loading dose volume to be infused (VTBI) and primary rate were not adjusted during the setup. Eight hours and 58minutes later, the loading dose VTBI reached 0mL and the pump reverted to the historical primary rate of 999mL/hour. The event log showed that 37.1mL of NORepinephrine was infused resulting in an equivalent calculated bolus dose of 1.8mg administered in two minutes. The patient suffered a cardiac arrest and the infusion was stopped. No faults were found with the pump. Herein, we discuss our analysis of the pump event logs and propose further safety strategies and interventions. PMID- 26364124 TI - Characterization of annexin A2 in chicken follicle development: Evidence for its involvement in angiogenesis. AB - Annexin A2 (ANXA2) is a calcium-dependent, phospholipid-binding protein found in various cells and tissues. ANXA2 plays multiple roles in regulating cellular functions and is often over-expressed in different types of tumors including ovarian cancer. Others and we previously found that ANXA2 was up-regulated in the ovaries of hens with higher laying rate, indicated that ANXA2 is involved in avian follicle development. In this study, we found that ANXA2 mRNA expression increased during chicken ovary maturation and follicle development. In the pre ovulatory follicles, ANXA2 expression level was significantly higher in theca cells than granulosa cells. In theca cells, ANXA2 expression could be stimulated by follicle-stimulating hormone (FSH) and estrogen but not luteinizing hormone (LH) or progesterone. The core promoter regions control the basal and FSH-induced ANXA2 gene expression were identified. Forced expression of ANXA2 could induce the expression of angiogenic factors and receptors in theca cells. Furthermore, ANXA2 overexpression resulted increased vascular endothelial growth factor A (VEGFA) secretion and theca cell proliferation. Current study not only provides the first evidence of expression and regulation of ANXA2 in chicken ovary, but also suggests that ANXA2 is involved in follicular angiogenesis and contributes to successful follicle development and ovulation. PMID- 26364125 TI - Mass sperm motility is associated with fertility in sheep. AB - The study was to focus on the relationship between wave motion (mass sperm motility, measured by a mass sperm motility score, manually assessed by artificial insemination (AI) center operators) and fertility in male sheep. A dataset of 711,562 artificial inseminations performed in seven breeds by five French AI centers during the 2001-2005 time period was used for the analysis. Factors influencing the outcome of the insemination, which is a binary response observed at lambing of either success (1) or failure (0), were studied using a joint model within each breed and AI center (eight separate analyses). The joint model is a multivariate model where all information related to the female, the male and the insemination process were included to improve the estimation of the factor effects. Results were consistent for all analyses. The male factors affecting AI results were the age of the ram and the mass motility. After correction for the other factors of variation, the lambing rate increased quasi linearly from three to more than ten points with the mass sperm motility score depending on the breed and the AI center. The consistency of the relationship for all breeds indicated that mass sperm motility is predictive of the fertility resulting when sperm are used from a specific ejaculate. Nonetheless, predictability could be improved if an objective measurement of mass sperm motility were available as a substitute for the subjective scoring currently in use in AI centers. PMID- 26364126 TI - Learning in the workplace: the role of Nurse Managers. AB - Objective This research explores Nurse Managers' (NMs') influence on workplace learning. The facilitation of staff learning has implications for the role of NMs, who are responsible for the quality and safety of patient care. However, this aspect of their work is implicit and there is limited research in the area. Methods This paper discusses the findings from one hospital as part of a broader philosophical hermeneutic study conducted in two public hospitals over a 20-month timeframe. NMs participated in interviews, a period of observation, follow-up interviews and a focus group. Transcribed data was thematically analysed. Eraut's 'Two triangle theory of workplace learning' was used to interpret participants' accounts of how they facilitated workplace learning. Findings The analysis found that NMs worked to positively influence staff performance through learning in three domains: orientating new staff, assessing staff performance and managing underperformance. Conclusions This study purports that NMs influence workplace learning in ways that are seldom recognised. A more conscious understanding of the impact of their role can enable NMs to more purposefully influence workplace learning. Such understanding also has implications for the professional preparation of NMs for their role in the context of workplace learning, facilitating learning for change and enabling the advancement of quality and safety in healthcare. What is known about the topic? Studies exploring the influence of Nurse Managers in workplace learning have been limited to their role in the facilitation of formal learning. There is a paucity of research that examines their role in influencing informal learning. What does this paper add? The findings of this study draw on Eraut's 'Two triangle theory of workplace learning' to further define the interdependent relationship between management and educational practices. What are the implications for practitioners? NMs' awareness and deliberate use of their management role to enhance workplace learning will not only strengthen their role, but will also foster good learning environments and quality nursing services. PMID- 26364127 TI - Neurobiological underpinnings of sensation seeking trait in heroin abusers. AB - Neurobiological investigation of heroin revealed that abusers of this highly addictive substance show dysregulation in brain circuits for reward processing and cognitive control. Psychologically, personality traits related to reward processing and cognitive control differed between heroin abusers and non-abusers. Yet, there is no direct evidence on the relationship between these neurobiological and psychological findings on heroin abusers, and whether such relationship is altered in these abusers. The present study filled this research gap by integrating findings obtained via magnetic resonance imaging (structural volume and resting-state functional connectivity) and self-reported personality trait measures (Zuckerman's Sensation Seeking Scale and Barratt Impulsivity Scale) on 33 abstinent heroin users and 30 matched healthy controls. The key finding is a negative relationship between high sensation seeking tendency and midbrain structural volume in the heroin users. Importantly, there was stronger coupling between the midbrain and ventromedial prefrontal cortex and weaker coupling between the midbrain and dorsolateral prefrontal cortex in heroin users. Our findings offer significant insight into the neural underpinning of sensation seeking in heroin users. Importantly, the data shed light on a novel relationship between the mesolimbic-prefrontal pathway of the reward system and the high sensation seeking personality trait in heroin abusers. PMID- 26364128 TI - Author's response. AB - I am grateful to Andrew Leaver in his role as chairman of the NSW Chapter of Musculoskeletal Physiotherapy Australia for raising issues pertinent to our paper. It is this interest that encourages debate and helps to evolve further the ideas on a topic that has not been investigated previously. PMID- 26364130 TI - Molar absorption coefficients and stability constants of metal complexes of 4-(2 pyridylazo)resorcinol (PAR): Revisiting common chelating probe for the study of metalloproteins. AB - 4-(2-Pyridylazo)resorcinol (PAR) is one of the most popular chromogenic chelator used in the determination of the concentrations of various metal ions from the d, p and f blocks and their affinities for metal ion-binding biomolecules. The most important characteristics of such a sensor are the molar absorption coefficient and the metal-ligand complex dissociation constant. However, it must be remembered that these values are dependent on the specific experimental conditions (e.g. pH, solvent components, and reactant ratios). If one uses these values to process data obtained in different conditions, the final result can be under- or overestimated. We aimed to establish the spectral properties and the stability of PAR and its complexes accurately with Zn(2+), Cd(2+), Hg(2+), Co(2+), Ni(2+), Cu(2+), Mn(2+) and Pb(2+) at a multiple pH values. The obtained results account for the presence of different species of metal-PAR complexes in the physiological pH range of 5 to 8 and have been frequently neglected in previous studies. The effective molar absorption coefficient at 492 nm for the ZnHx(PAR)2 complex at pH7.4 in buffered water solution is 71,500 M(-1) cm(-1), and the dissociation constant of the complex in these conditions is 7.08*10(-13) M(2). To confirm these values and estimate the range of the dissociation constants of zinc-binding biomolecules that can be measured using PAR, we performed several titrations of zinc finger peptides and zinc chelators. Taken together, our results provide the updated parameters that are applicable to any experiment conducted using inexpensive and commercially available PAR. PMID- 26364129 TI - An asbestos-exposed family with multiple cases of pleural malignant mesothelioma without inheritance of a predisposing BAP1 mutation. AB - We report a family with domestic exposure to asbestos and diagnosis of multiple cancers, including eight pleural malignant mesotheliomas and several other lung or pleural tumors. DNA sequence analysis revealed no evidence for an inherited mutation of BAP1. Sequence analysis of other potentially relevant genes, including TP53, CDKN2A, and BARD1, also revealed no mutation. DNA microarray analysis of tissue from two mesotheliomas revealed multiple genomic imbalances, including consistent losses of overlapping segments in 2q, 6q, 9p, 14q, 15q, and 22q, but no losses of chromosome 3 harboring the BAP1 locus. However, the results of immunohistochemical analysis demonstrated loss of nuclear BAP1 staining in three of six mesotheliomas tested, suggesting that somatic alterations of BAP1 occurred in a subset of tumors from this family. Since mesothelioma could be confirmed in only a single generation, domestic exposure to asbestos may be the predominant cause of mesothelioma in this family. Given the existence of unspecified malignant pleural tumors and lung cancers in a prior generation, we discuss the possibility that some other tumor susceptibility or modifier gene(s) may contribute to the high incidence of mesothelioma in this family. Because the incidence of mesothelioma in this family is higher than that expected even in workers heavily exposed to asbestos, we conclude that both asbestos exposure and genetic factors have played a role in the high rate of mesothelioma and potentially other pleural or lung cancers seen in this family. PMID- 26364131 TI - Comparative solution equilibrium studies on pentamethylcyclopentadienyl rhodium complexes of 2,2'-bipyridine and ethylenediamine and their interaction with human serum albumin. AB - Complex formation equilibrium processes of the (N,N) donor containing 2,2' bipyridine (bpy) and ethylenediamine (en) with (eta(5) pentamethylcyclopentadienyl)rhodium(III) were investigated in aqueous solution via pH-potentiometry, (1)H NMR spectroscopy, and UV-vis spectrophotometry in the absence and presence of chloride ions. The structure of [RhCp*(en)Cl]ClO4 (Cp*, pentamethylcyclopentadienyl) was also studied by single-crystal X-ray diffraction. pKa values of 8.56 and 9.58 were determined for [RhCp*(bpy)(H2O)](2+) and [RhCp*(en)(H2O)](2+), respectively resulting in the formation of negligible amount of mixed hydroxido complexes at pH 7.4. Stability and the H2O/Cl(-) co-ligand exchange constants of bpy and en complexes considerably exceed those of the bidentate O-donor deferiprone. The strong affinity of the bpy and en complexes to chloride ions most probably contributes to their low antiproliferative effect. Interactions between human serum albumin (HSA) and [RhCp*(H2O)3](2+), its complexes formed with deferiprone, bpy and en were also monitored by (1)H NMR spectroscopy, ultrafiltration/UV-vis and spectrofluorometry. Numerous binding sites (>= 8) are available for [RhCp*(H2O)3](2+); and the interaction takes place most probably via covalent bonds through the imidazole nitrogen of His. According to the various fluorescence studies [RhCp*(H2O)3](2+) binds on sites I and II, and coordination of surface side chain donor atoms of the protein is also feasible. The binding of the bpy and en complex is weaker and slower compared to that of [RhCp*(H2O)3](2+), and formation of ternary HSA-RhCp*-ligand adducts was proved. In the case of the deferiprone complex, the RhCp* fragment is cleaved off when HSA is loaded with low equivalents of the compound. PMID- 26364132 TI - Human sparganosis, a neglected food borne zoonosis. AB - Human sparganosis is a food borne zoonosis caused by the plerocercoid larvae (spargana) of various diphyllobothroid tapeworms of the genus Spirometra. Human infections are acquired by ingesting the raw or undercooked meat of snakes or frogs, drinking untreated water, or using raw flesh in traditional poultices. More than 1600 cases of sparganosis have been documented worldwide, mostly in east and southeast Asia. Sporadic cases have been reported in South America, Europe, and Africa, and several cases have been described in travellers returning from endemic regions. Epidemiological data suggest that the increased effect of sparganosis on human health is because of greater consumption of raw meat of freshwater frogs and snakes. This Review provides information about the Spirometra parasites and their lifecycles, summarises clinical features, diagnosis, and treatment of human sparganosis, and describes geographical distribution and infection characteristics of Spirometra parasites in host animals. PMID- 26364133 TI - High-resolution genetic profile of viral genomes: why it matters. AB - The approval of novel antiviral treatments for hepatitis C virus (HCV) infection provides a great example of research driven medicine in action. However, the emergence of resistant viral strains to existing treatments reminds us of the ongoing challenge that we still face in HCV therapy. What can be done to minimize the health risk posed by viral variants that develop resistance and cause failure of therapy? Here we propose that a high-resolution genetic profiling approach that can assess the function at a single nucleotide/amino acid resolution, may provide a solution. We further discuss the potential application of this methodology in resolving viral resistance through the following three aspects: (1) high-resolution mapping of inflexible regions on the viral genome to identify better drug targets; (2) exhaustive drug resistance profiles to facilitate next generation drug design; (3) coupled with closely monitoring within-host virus quasi-species, drug resistance profiles can aid in optimized drug combination and personalized medicine in HCV treatments. PMID- 26364135 TI - [Survival of lung cancer patients treated at a referral hospital in Zaragoza (Spain)]. AB - OBJECTIVE: The aim of this work is to study the survival of lung cancer patients treated at a referral hospital in Zaragoza (Spain). MATERIAL AND METHOD: The Kaplan-Meier test was used to calculate observed survival. The automatic calculation of the Catalan Institute of Oncology was used to analyse relative survival. RESULTS: Mean survival time was 25.74 months. There was no difference when comparing age groups (P=.151), gender (P=.369), and histological type of tumour (P=.086). Survival by stage of the disease at diagnosis revealed statistically significant differences (P<.001). Relative survival 5 years after diagnosis for the group analysed was 14%. Survival was higher for men (15.5%), in patients under 60 (16.7%) and squamous tumours (18.7%). CONCLUSIONS: Survival by tumour stage was in line with the TNM Staging System for Lung Cancer. These results suggest that overall survival rate for lung cancer in Zaragoza remains very low in the long term, and this depends on the stage of the disease at diagnosis. PMID- 26364134 TI - Influenza virus-host interactomes as a basis for antiviral drug development. AB - Currently, antiviral drugs that target specific viral protein functions are available for the treatment of influenza; however, concern regarding the emergence of drug-resistant viruses is warranted, as is the urgent need for new antiviral targets, including non-viral targets, such as host cellular factors. Viruses rely on host cellular functions to replicate, and therefore a thorough understanding of the roles of virus-host interactions during influenza virus replication is essential to develop novel anti-influenza drugs that target the host factors involved in virus replication. Here, we review recent studies that used several approaches to identify host factors involved in influenza virus replication. These studies have permitted the construction of an interactome map of virus-host interactions in the influenza virus life cycle, clarifying the entire life cycle of this virus and accelerating the development of new antiviral drugs with a low propensity for the development of resistance. PMID- 26364136 TI - The evolving role of the masseter-to-facial (V-VII) nerve transfer for rehabilitation of the paralyzed face. AB - In cases where the proximal stump of the facial nerve is unavailable for repair or interposition nerve grafting, and there are intact distal facial nerve branches and viable mimetic muscles, then the masseter-to-facial (V-VII) nerve transfer can provide an effective means of smile restoration. Positive attributes of the V-VII transfer include: limited donor site morbidity, anatomic consistency, a dense population of myelinated motor nerve fibers capable of producing strong motion, synergy with the facial nerve and potential for effective cerebral adaptation yielding an effortless smile. The technique can be utilized in isolation or combined with cross face nerve grafts to further enhance spontaneity and resting tone. PMID- 26364137 TI - Lipofilling, an efficient solution for breast sequelae after cardiothoracic surgery. AB - Evolutions in pediatric cardiovascular surgery have allowed the treatment of a various range of cardiovascular malformations in infants. It is a difficult branch of surgery, with vital impact, which can also leave residual thoracic scars, possible sources for thoracomammary deformities in adults. Most thoracomammary deformities after thoracotomy are observed at puberty, when they appear as breast asymmetries. The main cause is the breast bud injured during thoracotomy. Several techniques have been suggested for breast reconstruction, but none give satisfying results. We have been practicing lipofilling since 1998 for breast reconstruction. Since 2001, we have started applying it to breast deformities. The final result is constant in time, natural, and has a good volume filler effect. We describe the fat grafting technique, an original technique, as a solution for this kind of deformities. The technique is illustrated by two clinical cases. In conclusion, fat grafting has really improved breast asymmetry due to iatrogenic deformation. Even if those cases are rare, surgeons have to know this kind of procedure. It is indeed a simple and efficient solution for those patients after childhood, with natural and long standing results. PMID- 26364139 TI - Do we really need to use our smartphones while driving? AB - Smartphone usage while driving, a prominent type of driver distraction, has become a major concern in the area of road safety. Answers to an internet survey by 757 Israeli drivers who own smartphones were analyzed with focus on two main purposes: (1) to gain insights regarding patterns of smartphone usage while driving and its motivation, (2) to probe drivers' views on the perceived risk and the need to use smartphones while driving, as well as their willingness to use blocking apps that limit such usages. Phone calls and texting were found to be the most common usages while driving, hence, both were chosen to be further analyzed. 73% (N=551) of the respondents make phone calls while driving and almost half of them may be considered frequent callers as they admit to do it intensively while driving. As for texting, 35% of the respondents (N=256) text while driving and a quarter of them do so frequently. While phone calls were perceived to compromise safety by 34% of the users, texting was perceived to compromise safety by 84% of the users. However, we found that drivers place limitations on themselves as more than 70% avoid texting when they think they need to devote attention to driving. A logistic regression model indicates that perceived need and perceived safety are significant factors associated with being a frequent smartphone phone calls user, but only perceived need significantly predicts being a frequent texting user. Approximately half of all the respondents are willing to try an app which blocks smartphone usage while driving. The willingness to use such technology was found to be related primarily to perceived need. Less significant factors are work-related usage and perceived safety. Frequency of usage was not found to affect this willingness, indicating that it should not be a factor in designing and implementing interventions to limit smartphone usage while driving. PMID- 26364140 TI - Examining signs of driver sleepiness, usage of sleepiness countermeasures and the associations with sleepy driving behaviours and individual factors. AB - The impairing effect from sleepiness is a major contributor to road crashes. The ability of a sleepy driver to perceive their level of sleepiness is an important consideration for road safety as well as the type of sleepiness countermeasure used by drivers as some sleepiness countermeasures are more effective than others. The aims of the current study were to determine the extent that the signs of driver sleepiness were associated with sleepy driving behaviours, as well as determining which individual factors (demographic, work, driving, and sleep related factors) were associated with using a roadside or in-vehicle sleepiness countermeasure. A sample of 1518 Australian drivers from the Australian State of New South Wales and the neighbouring Australian Capital Territory took part in the study. The participants' experiences with the signs of sleepiness were reasonably extensive. A number of the early signs of sleepiness (e.g., yawning, frequent eye blinks) were related with continuing to drive while sleepy, with the more advanced signs of sleepiness (e.g., difficulty keeping eyes open, dreamlike state of consciousness) associated with having a sleep-related close call. The individual factors associated with using a roadside sleepiness countermeasure included age (being older), education (tertiary level), difficulties getting to sleep, not continuing to drive while sleepy, and having experienced many signs of sleepiness. The results suggest that these participants have a reasonable awareness and experience with the signs of driver sleepiness. Factors related to previous experiences with sleepiness were associated with implementing a roadside countermeasure. Nonetheless, the high proportions of drivers performing sleepy driving behaviours suggest that concerted efforts are needed with road safety campaigns regarding the dangers of driving while sleepy. PMID- 26364138 TI - Abrasion arthroplasty increases mesenchymal stem cell content of postoperative joint effusions. AB - BACKGROUND: Abrasion arthroplasty (AAP) is a procedure by which intrinsic cartilage healing is believed to be stimulated. Although clinically accepted for degenerative and traumatic cartilage lesions scientific evidence at a molecular level that proves the effect of AAP is scarce. METHOD: Mononuclear cells were extracted from postoperative joint effusions 21.5 h post AAP and simple debridement of cartilage lesions. Luminex, ELISA and FACS experiments were performed. Immunohistochemical stainings of cell cultures for cartilage markers were used to confirm the findings. RESULTS: Postoperative joint effusions after AAP showed increased contents of Mononuclear cells compared to Arthroscopic Chondroplasty (ACP). BMP-4 and IGF were increased in AAP as complared to ACP. Mononuclear cells isolated after AAP express the MSC markers CD 73, CD 105, CD 90, CD 44 and are CD34 negative. Chondrogenic differentiation was demonstrated by positive staining for Sox9, collagen II, proteoglycan, chondroitin-4-sulfate. CONCLUSION: Our results support the clinical application of AAP as a procedure that enhances cartilage repair as an alternative to far more complex procedures that have gained popularity. Furthermore the data presented supports clinical investigations that recommend not to use suction drainage as by this procedure a considerable amount of the regeneratory potential of postoperative joint effusions might be extracted. PMID- 26364141 TI - Effects of ROS-relative NF-kappaB signaling on high glucose-induced TLR4 and MCP 1 expression in podocyte injury. AB - High glucose (HG) induced inflammation is central to progression in diabetic nephropathy (DN). Recent studies have suggested that nuclear factor-kappa B (NF kappaB) signaling activation is associated with DN, and podocyte damage may be involved in orchestrating these effects. Therefore, the aim of this study was to investigate the effects of NF-kappaB signaling on podocytes under HG conditions. The effects of HG and NF-kappaB signaling on podocytes were assessed by CCK-8 assay, cellular NF-kappaB translocation assay, measurement of reactive oxygen species (ROS) and Western blot analysis. We found that HG reduced cell viability, activated NF-kappaB signaling and up-regulated toll-like receptor 4 (TLR4) and monocyte chemoattractant protein-1 (MCP-1). In these cells, NF-kappaB inhibition with ammonium pyrrolidinethiocarbamate (PDTC) resulted in effectively constraining TLR4 and MCP-1 up-regulation, indicating that protective effects associated with the inhibition of NF-kappaB were linked to TLR4 and MCP-1 down regulation in podocytes. Furthermore, HG significantly increased the production of intracellular ROS. Pretreatment with N-acetyl-l-cysteine (NAC) significantly inhibited intracellular ROS generation and increased cell viability, accompanied by a significant NF-kappaB inhibition and suppression of TLR4 and inflammatory cytokine MCP-1 expression. Collectively, our novel data suggest that HG induces the over-experssion of TLR-4 and MCP-1 through a NF-kappaB-dependent signaling. NF-kappaB-mediated increased inflammation is possibly via ROS and contributes to the cell injury. These results may provide potential therapeutic target for diabetic nephropathy in the future. PMID- 26364142 TI - Phenotype and functions of B cells in patients with acute brain injuries. AB - BACKGROUND: Brain injuries (BI) induce a state of systemic immunosuppression, leading to a high risk of pneumonia. In this pilot study, we investigated the status of B cell compartment in BI patients. METHODS: A prospective observational study was performed in 2 intensive care units in a university hospital. Blood samples were collected in 14 patients at day 1 and day 7 after acute BI. The phenotype and the ability of B cells to secrete IL-10 were compared to 11 healthy volunteers (HV). RESULTS: Among the circulating lymphocytes, the frequency of B cells was significantly higher in BI patients compared to HV (p<0.001). B cells from BI patients displayed an activated profil on day 7 after BI, reflected by a significantly higher proportion of CD27(+) memory (p=0.01) and CD27(+) IgD(-) switched memory B cells (p=0.02), as well as a significantly higher blood level of IgA (p=0.001) and IgM (p<0.001) as compared to day 1. The frequency of IL-10 secreting B cells (IL-10(+) B cells) on day 1 and day 7 was significantly lower in BI patients compared to HV (p<0.05). Interestingly, we observed that all BI patients with high frequency of IL-10(+) B cells on day 1 displayed an episode of pneumonia, and had a longer duration of mechanical ventilation and ICU stay compared to BI patients with low proportion of IL-10(+) B cells. CONCLUSION: This study provides an extensive description of the phenotype and function of B cells in BI patients. Our results suggest that IL-10(+) B cells could play a major role in immunosuppression after BI. PMID- 26364143 TI - Investigation of a panel of monoclonal antibodies and polyclonal sera against anthrax toxins resulted in identification of an anti-lethal factor antibody with disease-enhancing characteristics. AB - Hybridomas were created using spleen of mice that were actively immunized with rLFn (recombinant N-terminal domain of lethal factor). Later on, separate group of mice were immunized with rLFn to obtain a polyclonal control for passive immunization studies of monoclonal antibodies. This led to the identification of one cohort of rLFn-immnized mice that harboured disease-enhancing polyclonal antibodies. At the same time, the monoclonal antibodies secreted by all the hybridomas were being tested. Two hybridomas secreted monoclonal antibodies (H10 and H8) that were cross-reactive with EF (edema factor) and LF (lethal factor), while the other two hybridomas secreted LF-specific antibodies (H7 and H11). Single chain variable fragment (LETscFv) was derived from H10 hybridoma. H11 was found to have disease-enhancing property. Combination of H11 with protective monoclonal antibodies (H8 and H10) reduced its disease enhancing nature. This in vitro abrogation of disease-enhancement provides the proof of concept that in polyclonal sera the disease enhancing character of a fraction of antibodies is overshadowed by the protective nature of the rest of the antibodies generated on active immunization. PMID- 26364144 TI - In vitro bioactivity of BiorootTM RCS, via A4 mouse pulpal stem cells. AB - OBJECTIVE: To evaluate the biocompatibility and osteoinductive properties of BiorootTM RCS (BR, Septodont, France) compared to Kerr's Pulp Canal SealerTM (PCS, Kerr, Italy) using the mouse pulp-derived stem cell line A4, which have an osteo/odontogenic potential in vitro and contribute to efficient bone repair in vivo. METHODS: A4 cells were cultured at the stem cell stage in the presence of solid disks of BR or PCS, whereas untreated A4 cells were used as control. After 3, 7, 10 days of direct contact with the sealers, cell viability was quantified using Trypan Blue exclusion assay. Immunolabelings were performed to assess the expression of odontoblast markers i.e. type 1 collagen, DMP1 or BSP. Finally, sealer-treated cells were induced toward osteo/odontogenic differentiation to assess the impact of the sealers on mineralization by Von Kossa staining. Statistical significance was evaluated by one-way analysis of variance and t-test (p<0.05). RESULTS: BR did not alter the viability and morphology of A4 pulpal cells compared to control group (p>0.05); however, living cell percentage of PCS was significantly lower compared to control and BR groups (p<0.05). BR preserved the intrinsic ability of A4 cells to express type 1 collagen, DMP1 or BSP at the stem cell stage. It did not alter the integrity of collagen fibers surrounding the cells and promoted overexpression of BSP and DMP1 at the cell surface. In contrast to PCS, BR did not compromise the mineralization potential of pulpal A4 stem cells. SIGNIFICANCE: BiorootTM RCS was not as cytotoxic as PCS. It did not recruit the pulpal stem cells toward differentiation but preserve their osteo odontogenic intrinsic properties. BiorootTM RCS might provide more suitable environment to induce stem cells for hard tissue deposition. PMID- 26364145 TI - Prognostic Implications of Tumor-Infiltrating Lymphocytes in Association With Programmed Death Ligand 1 Expression in Early-Stage Breast Cancer. AB - BACKGROUND: The immune system might influence breast cancer (BC) prognosis. However, the relationship between programmed death ligand 1 (PD-L1) and tumor infiltrating lymphocyte (TIL) profiles remains unclear with respect to BC subtypes. PATIENTS AND METHODS: We investigated the relationship between TIL profiles for CD8+ and forkhead box P3-positive (FOXP3+) and PD-L1 expression in primary tumor tissue using immunohistochemistry and the clinical outcomes in 2 patient cohorts at the National Cancer Center: 256 patients diagnosed with early stage BC from January 2001 to December 2005 and 77 hormone receptor (HR)-negative BC patients diagnosed from January 2006 to December 2008. Clinical data were collected, including HR status, human epidermal growth factor receptor 2 expression, disease-free survival, and overall survival (OS). RESULTS: The median patient age was 47 years (range, 28-78), and the median follow-up period was 9.8 years. Of the 333 patients, 186 (55.9%) had HR-positive and 125 (37.5%) had node positive BC. We found a strong positive correlation between CD8+ TILs and FOXP3+ TILs (P < .001). CD8+ TILs were more abundant in tumors with low PD-L1 expression (P < .001), although no association was found between FOXP3+ TILs and PD-L1 expression. More CD8+ TILs were present in HR-negative than in HR-positive BC (P < .001), and PD-L1 expression was more frequent in HR-positive BC (P < .001). A greater number of CD8+ TILs (increase in quartile) was strongly associated with OS (hazard ratio, 0.61; 95% confidence interval, 0.39-0.95; P = .03) only in HR negative BC when adjusted for various clinical factors. PD-L1 expression and FOXP3+ TILs did not exhibit such associations. CONCLUSION: Higher CD8+ lymphocyte infiltration was related to lower PD-L1 expression and higher FOXP3+ TIL infiltration in BC. Higher CD8+ TIL expression was associated with prolonged survival only in those with HR-negative BC. PMID- 26364146 TI - ED patient satisfaction: factors associated with satisfaction with care. PMID- 26364147 TI - Laparoscopic management for spontaneous rupture of left gastroepiploic vessel after forceful retching. AB - Spontaneous rupture of the left gastroepiploic vessel causing abdominal apoplexy or spontaneous hemoperitoneum is extremely rare. Such ambiguous condition can delay diagnosis, resulting in hypovolemic shock. Reporting such rare cases is valuable to clinicians. Here, we report a 19-year-old man who initially presented left upper quadrant pain and diaphoresis followed by vomiting after ingesting alcohol. He was diagnosed with diffuse hemoperitoneum and large amount of hematoma in left side of lesser sac due to spontaneous rupture of left gastroepiploic vessel. The patient underwent emergency exploratory laparoscopy. Bleeding was controlled by clipping the teared vessel. PMID- 26364148 TI - Elderly fall patients triaged to the trauma bay: age, injury patterns, and mortality risk. AB - BACKGROUND: Falls in the elderly are a significant cause of morbidity and mortality. We sought to better categorize this patient population and describe factors contributing to their falls. METHODS: This is a retrospective review of geriatric patients presenting to a level 1 community trauma center. We queried our trauma database for all patients 65 years and older presenting with fall and triaged to the trauma bay from 2008 to 2013. Researchers reviewed the patients' trauma intake paperwork to assess mechanism, injury, and location of fall, whereas discharge summaries were reviewed to determine disposition, morbidity, and mortality. RESULTS: A total of 650 encounters were analyzed. Five hundred thirty-nine resided at home (82.9%), 110 presented from nursing homes or assisted living (16.9%), and 1 came from hospice (0.15%). Ninety-five patients died or were placed on hospice as a result of their falls (14.7%), of which 88 came from home. Controlling for Injury Severity Score, living at home was an independent risk factor for fall-related mortality (odds ratio, 3.0). Comparing the elderly (age 65-79 years; n = 274) and the very elderly (age >=80 years; n = 376), there were no differences in Injury Severity Score (P = .33), likelihood of death (P = .49), likelihood of C-spine injury (P = 1.0), or likelihood of other axial or long bone skeletal injury (P = .23-1.0). There was a trend for increased likelihood of head injury in very elderly patients (P = 0.06). CONCLUSION: Prevention measures to limit morbidity and mortality in elderly fall patients should be aimed at the home setting, where most severe injuries occur. Very elderly patients may be at increased risk for intracranial fall-related injuries. PMID- 26364149 TI - Quantification of type VI secretion system activity in macrophages infected with Burkholderia cenocepacia. AB - The Gram-negative bacterial type VI secretion system (T6SS) delivers toxins to kill or inhibit the growth of susceptible bacteria, while other secretion systems target eukaryotic cells. Deletion of atsR, a negative regulator of virulence factors in B. cenocepacia K56-2, increases T6SS activity. Macrophages infected with a K56-2 DeltaatsR mutant display dramatic alterations in their actin cytoskeleton architecture that rely on the T6SS, which is responsible for the inactivation of multiple Rho-family GTPases by an unknown mechanism. We employed a strategy to standardize the bacterial infection of macrophages and densitometrically quantify the T6SS-associated cellular phenotype, which allowed us to characterize the phenotype of systematic deletions of each gene within the T6SS cluster and ten vgrG genes in K56-2 DeltaatsR. None of the genes from the T6SS core cluster nor the individual vgrG genes were directly responsible for the cytoskeletal changes in infected cells. However, a mutant strain with all vgrG genes deleted was unable to cause macrophage alterations. Despite not being able to identify a specific effector protein responsible for the cytoskeletal defects in macrophages, our strategy resulted in the identification of the critical core components and accessory proteins of the T6SS assembly machinery and provides a screening method to detect T6SS effectors targeting the actin cytoskeleton in macrophages by random mutagenesis. PMID- 26364154 TI - Determinants of recent HIV testing among male sex workers and other men who have sex with men in Shenzhen, China: a cross-sectional study. AB - We recruited 510 male sex workers (also referred as 'money boys' (MBs) and 533 other men who have sex with men (MSM) to investigate determinants of recent (last year) HIV testing in Shenzhen, China. Overall, 43% of MBs and 48% of other MSM reported having been tested for HIV in the last year. The most important determinant of testing among MBs was having multiple anal sex partners; among other MSM, the most important determinants were having a homosexual orientation and having a history of sexually transmissible infection. For MBs, education programs are needed to increase their awareness of actual HIV risk. For other MSM, destigmatising programs are needed. PMID- 26364155 TI - Classification of illicit heroin by UPLC-Q-TOF analysis of acidic and neutral manufacturing impurities. AB - The illicit manufacture of heroin results in the formation of trace levels of acidic and neutral manufacturing impurities that provide valuable information about the manufacturing process used. In this work, a new ultra performance liquid chromatography-quadrupole-time of flight mass spectrometry (UPLC-Q-TOF) method; that features high resolution, mass accuracy and sensitivity for profiling neutral and acidic heroin manufacturing impurities was developed. After the UPLC-Q-TOF analysis, the retention times and m/z data pairs of acidic and neutral manufacturing impurities were detected, and 19 peaks were found to be evidently different between heroin samples from "Golden Triangle" and "Golden Crescent". Based on the data set of these 19 impurities in 150 authentic heroin samples, classification of heroin geographic origins was successfully achieved utilizing partial least squares discriminant analysis (PLS-DA). By analyzing another data set of 267 authentic heroin samples, the developed discrimiant model was validated and proved to be accurate and reliable. PMID- 26364156 TI - The characteristics of post-neurosurgical bacterial meningitis in elective neurosurgery in 2012: A single institute study. AB - OBJECTIVE: Most post-neurosurgical meningitis research has been focused on large cohorts with numerous cases followed over several years. However, the characteristics of post-neurosurgical meningitis in an entire single year are still unclear, and knowledge of these characteristics might influence the selection of appropriate antibiotics and therapeutic strategies for the successful management of this disease. Our aim is to obtain a better understanding of post-neurosurgical meningitis over a single entire year. MATERIALS AND METHODS: Patients with positive meningitis cultures after neurosurgical operations in our hospital during the entire year of 2012 were included in the analysis. We report demographic characteristics, morbidity during different seasons, clinical and bacteriological profiles, sensitivity to antibiotics and causes of the post-neurosurgical meningitis infections in our cohort. RESULTS: Of the 6407 patients who underwent neurosurgical procedures during the study period, 146 developed post-neurosurgical meningitis and the overall incidence of meningitis was 2.28%. The incidence of meningitis was significantly higher in patients who underwent surgery in the autumn and winter than spring or summer (p=0.000). The most common organisms causing meningitis were Gram-positive bacteria, followed by the Klebsiella and Baumannii species. Compound sulfamethoxazole (52.6%) and vancomycin (10.5%) were the most active antibiotics against Gram-positive bacteria strains, whereas meropenem (43.8%) and polymyxin (18.8%) were active against Gram-negative bacillus strains. CONCLUSIONS: Post-neurosurgical meningitis usually occurs in the autumn and winter of the year in our hospital. Gram-positive organisms, which are sensitive to compound sulfamethoxazole and vancomycin, are the most common causative pathogens of post-neurosurgical meningitis in the northern mainland of China. PMID- 26364157 TI - Retrospective analysis on correlation factors of preserving the ligamentum flavum in microendoscopic discectomy. AB - OBJECTIVE: The present study was conducted to investigate the correlation factors of successful preservation of the ligamentum flavum (LF) in microendoscopic discectomy. METHODS: This retrospective review was carried out on 78 consecutive patients who underwent single segment microendoscopic discectomy projecting to preserve the LF between January 2012 to January 2013. The demographic and clinical data including age, gender, duration of disease, area of interlaminar space, disc level and position type of lumbar disc herniation were recorded. Intraoperative outcomes including duration of operation and peri-operative bleeding were recorded. Clinical outcomes were assessed by Oswestry disability index (ODI) and visual analog scale (VAS), and fibrosis formation was detected using computed tomographic scans with IV iopamidol injection. The follow up lasted six months. RESULTS: LF was successfully preserved in 54 patients (69.2%) and 24 patients (30.8%) underwent microendoscopic discectomy without preservation of LF. In multivariate logistic analysis, factors including age (OR, 1.17; 95% CI, 1.07-1.28; P<0.001) and area of the laminar space (OR, 0.09; 95% CI, 0.01 0.67; P=0.018) significantly associated with the preservation of LF. Other factors including gender, duration of ill course, disc level and position type seemed not associated with the preservation of the LF. In addition, there was no significant difference of the duration of the operation (P=0.689) as well as the peri-operative bleeding (P=0.147) between patients with preservation of the LF and patients without. However, patients with preservation of the LF showed significantly improved clinical outcomes (ODI: P=0.006, VAS: P=0.035) and less fibrosis formation than those without LF (P=0.018). CONCLUSIONS: Microendoscopic discectomy with preservation of the LF could achieve better clinical outcomes and less epidural fibrosis, while elder patients with smaller area of the laminar space should be deliberated on the preservation of the LF during the microendoscopic discectomy. PMID- 26364158 TI - Clinical evaluation of a multi-parameter customized respiratory TaqMan((r)) array card compared to conventional methods in immunocompromised patients. AB - BACKGROUND: Respiratory viral infections can cause significant morbidity and mortality in immunocompromised patients. Conventional tests routinely available at most institutions are limited by the number of detectable pathogens, by a poor sensitivity and/or a long turnaround time. OBJECTIVES: To compare the performance of routine conventional testing with direct fluorescent antibody assays and viral culture to a customized TaqMan(r) array card (TAC) real-time PCR method, targeting 24 viruses, 8 bacteria and 2 fungi simultaneously. STUDY DESIGN: We collected 143 respiratory samples from 120 symptomatic immunocompromised patients. Samples for which conventional and TAC results were discordant underwent further verification testing. RESULTS: The TAC assay identified viral pathogens in more samples than did conventional testing (77/143 versus 27/143; McNemar P<0.0001), even when TAC results for viruses that could not be detected by conventional testing were excluded from analysis (59/143 versus 26/143; P<0.0001). In addition, the TAC assay identified 18 samples with non-viral pathogens. Verification testing confirmed positive TAC results for 50 out of 55 samples for which conventional testing was negative. Two out of three samples with a positive conventional test but negative TAC result were confirmed positive. A viral and a total pathogen co-infection rate of 5.6% and 11.8% were found, respectively. CONCLUSIONS: The customized TAC assay resulted in a significantly increased identification of respiratory viruses. This study provides a practical real-life assessment of the performance of the TAC assay in a population for whom rapid and accurate diagnosis of viral and atypical pathogens is crucial for appropriate clinical management. PMID- 26364159 TI - Digoxin use after diagnosis of colorectal cancer and survival: a population-based cohort study. AB - BACKGROUND: Digoxin has been shown to affect a number of pathways that are of relevance to cancer, and its use has been associated with increased risks of breast and uterus cancer and, more recently, a 40% increase in colorectal cancer risk. These findings raise questions about the safety of digoxin use in colorectal cancer patients, and, therefore, we investigated whether digoxin use after colorectal cancer diagnosis increased the risk of colorectal cancer specific mortality. METHODS: A cohort of 10,357 colorectal cancer patients newly diagnosed from 1998 to 2009 was identified from English cancer registries and linked to the UK Clinical Practice Research Datalink (to provide digoxin and other prescription records) and to the Office of National Statistics mortality data (to identify 2,724 colorectal cancer-specific deaths). Using time-dependent Cox regression models, unadjusted and adjusted HRs and 95% confidence intervals (CI) were calculated for the association between postdiagnostic exposure to digoxin and colorectal cancer-specific mortality. RESULTS: Overall, 682 (6%) colorectal cancer patients used digoxin after diagnosis. Digoxin use was associated with a small increase in colorectal cancer-specific mortality before adjustment (HR, 1.25; 95% CI, 1.07-1.46), but after adjustment for confounders, the association was attenuated (adjusted HR, 1.10; 95% CI, 0.91-1.34) and there was no evidence of a dose response. CONCLUSIONS: In this large population-based colorectal cancer cohort, there was little evidence of an increase in colorectal cancer-specific mortality with digoxin use after diagnosis. IMPACT: These results provide some reassurance that digoxin use is safe in colorectal cancer patients. PMID- 26364160 TI - Hepatitis B virus infection and risk of nasopharyngeal carcinoma in southern China. AB - BACKGROUND: Whether or not hepatitis B virus (HBV) infection plays a role in the development of nasopharyngeal carcinoma (NPC) is largely unknown. Our study aimed to assess the association between HBV infection and the risk of NPC in Southern China. METHODS: We conducted a case-control study including 711 NPC cases and two groups of controls. The first control group consisted of 656 individuals with other benign tumors unrelated to HBV infection and the second group consisted of 680 healthy population controls. Multivariable ORs and corresponding 95% confidence intervals (CI) for NPC were estimated by logistic regression. RESULTS: Patients with NPC had higher prevalence of antibodies against hepatitis B core antigen-positive [anti-HBc-(+); 47.26%] compared with either benign tumor controls (39.33%; P < 0.01) or healthy controls (41.18%; P = 0.04). In multivariable models adjusting for a set of risk factors for NPC, anti-HBc-(+) was significantly associated with a higher risk of NPC [adjusted OR (AOR), 1.40; 95% CI, 1.12-1.74 compared with the benign tumor controls and AOR, 1.48; 95% CI, 1.05-2.08 compared with the healthy controls]. The association was not modified by hepatitis B surface antigen (HBsAg) status. Finally, compared with the healthy controls, individuals with both anti-HBc-(+) and EBV antibodies had largely increased risk of NPC (AOR, 141.82; 95% CI, 68.73-292.62). CONCLUSION: Our study suggests that HBV infection is associated with NPC risk in Southern China. IMPACT: Prevention for HBV infection may play a role in the development of NPC. PMID- 26364161 TI - Meta-analysis of vitamin D-binding protein and cancer risk. AB - BACKGROUND: Epidemiologic evidence supported a role for vitamin D and vitamin D receptor (VDR) polymorphisms in cancer risk. Beyond VDR, the biologic effects of vitamin D are mediated by the vitamin D-binding protein (DBP), a key protein in vitamin D metabolism. Furthermore, the gene encoding the DBP (GC, group-specific component) has an important role in the vitamin D pathway. Several studies investigated DBP serologic levels and GC polymorphisms in association with cancer risk with controversial results. Thus, we carried out a meta-analysis to investigate these associations. METHODS: We included 28 independent studies concerning the following tumors: basal cell carcinoma, bladder, breast, colon rectum, endometrium, liver, esophagus, stomach, melanoma, pancreas, prostate, and kidney. Through random-effect models, we calculated the summary odds ratios (SOR) for serum DBP and the GC polymorphisms rs2282679, rs12512631, rs7041, rs4588, rs17467825, rs1155563, and rs1352844. RESULTS: We found a borderline decrease in cancer risk for subjects with high compared with low levels of DBP [SOR, 0.75; 95% confidence interval (CI), 0.56-1.00]. Dose-response meta-analysis indicates a nonsignificant decrease risk for an increase of 1,000 nmol/L of DBP (SOR, 0.96; 95% CI, 0.91-1.01). We found no significant alterations in cancer risk for subjects carrying any of the studied GC polymorphisms compared with wild-type subjects both in the main analysis and in analyses stratified by cancer type and ethnicity. CONCLUSIONS: We found trends toward significance, suggesting a role of DBP in cancer etiology, which should be confirmed in further studies. IMPACT: To our knowledge, this is the first study to investigate GC polymorphisms and DBP serologic levels in association with any type of cancer. PMID- 26364162 TI - Pleiotropic analysis of cancer risk loci on esophageal adenocarcinoma risk. AB - BACKGROUND: Several cancer-associated loci identified from genome-wide association studies (GWAS) have been associated with risks of multiple cancer sites, suggesting pleiotropic effects. We investigated whether GWAS-identified risk variants for other common cancers are associated with risk of esophageal adenocarcinoma (EA) or its precursor, Barrett's esophagus. METHODS: We examined the associations between risks of EA and Barrett's esophagus and 387 SNPs that have been associated with risks of other cancers, by using genotype imputation data on 2,163 control participants and 3,885 (1,501 EA and 2,384 Barrett's esophagus) case patients from the Barrett's and Esophageal Adenocarcinoma Genetic Susceptibility Study, and investigated effect modification by smoking history, body mass index (BMI), and reflux/heartburn. RESULTS: After correcting for multiple testing, none of the tested 387 SNPs were statistically significantly associated with risk of EA or Barrett's esophagus. No evidence of effect modification by smoking, BMI, or reflux/heartburn was observed. CONCLUSIONS: Genetic risk variants for common cancers identified from GWAS appear not to be associated with risks of EA or Barrett's esophagus. IMPACT: To our knowledge, this is the first investigation of pleiotropic genetic associations with risks of EA and Barrett's esophagus. PMID- 26364163 TI - Interaction between common breast cancer susceptibility variants, genetic ancestry, and nongenetic risk factors in Hispanic women. AB - BACKGROUND: Most genetic variants associated with breast cancer risk have been discovered in women of European ancestry, and only a few genome-wide association studies (GWAS) have been conducted in minority groups. This research disparity persists in post-GWAS gene-environment interaction analyses. We tested the interaction between hormonal and lifestyle risk factors for breast cancer, and ten GWAS-identified SNPs among 2,107 Hispanic women with breast cancer and 2,587 unaffected controls, to gain insight into a previously reported gene by ancestry interaction in this population. METHODS: We estimated genetic ancestry with a set of 104 ancestry-informative markers selected to discriminate between Indigenous American and European ancestry. We used logistic regression models to evaluate main effects and interactions. RESULTS: We found that the rs13387042-2q35(G/A) SNP was associated with breast cancer risk only among postmenopausal women who never used hormone therapy [per A allele OR: 0.94 (95% confidence intervals, 0.74 1.20), 1.20 (0.94-1.53), and 1.49 (1.28-1.75) for current, former, and never hormone therapy users, respectively, Pinteraction 0.002] and premenopausal women who breastfed >12 months [OR: 1.01 (0.72-1.42), 1.19 (0.98-1.45), and 1.69 (1.26 2.26) for never, <12 months, and >12 months breastfeeding, respectively, Pinteraction 0.014]. CONCLUSIONS: The correlation between genetic ancestry, hormone replacement therapy use, and breastfeeding behavior partially explained a previously reported interaction between a breast cancer risk variant and genetic ancestry in Hispanic women. IMPACT: These results highlight the importance of understanding the interplay between genetic ancestry, genetics, and nongenetic risk factors and their contribution to breast cancer risk. PMID- 26364165 TI - In Memory of Dr. Paul Angulo (April 20, 1965 - February 25, 2015). PMID- 26364166 TI - Editorial Comment. PMID- 26364164 TI - Sex-specific associations of arsenic exposure with global DNA methylation and hydroxymethylation in leukocytes: results from two studies in Bangladesh. AB - BACKGROUND: Depletion of global 5-hydroxymethylcytosine (5-hmC) is observed in human cancers and is strongly implicated in skin cancer development. Although arsenic (As)-a class I human carcinogen linked to skin lesion and cancer risk-is known to be associated with changes in global %5-methylcytosine (%5-mC), its influence on 5-hmC has not been widely studied. METHODS: We evaluated associations of As in drinking water, urine, and blood with global %5-mC and %5 hmC in two studies of Bangladeshi adults: (i) leukocyte DNA in the Nutritional Influences on Arsenic Toxicity study (n = 196; 49% male, 19-66 years); and (ii) peripheral blood mononuclear cell DNA in the Folate and Oxidative Stress study (n = 375; 49% male, 30-63 years). RESULTS: Overall, As was not associated with global %5-mC or %5-hmC. Sex-specific analyses showed that associations of As exposure with global %5-hmC were positive in males and negative in females (P for interaction < 0.01). Analyses examining interactions by elevated plasma total homocysteine (tHcys), an indicator of B-vitamin deficiency, found that tHcys also modified the association between As and global %5-hmC (P for interaction < 0.10). CONCLUSION: In two samples, we observed associations between As exposure and global %5-hmC in blood DNA that were modified by sex and tHcys. IMPACT: Our findings suggest that As induces sex-specific changes in 5-hmC, an epigenetic mark that has been associated with cancer. Future research should explore whether altered %5-hmC is a mechanism underlying the sex-specific influences of As on skin lesion and cancer outcomes. PMID- 26364167 TI - Reply: To PMID 26135814. PMID- 26364168 TI - Prospective comparison of long term outcomes in patients with severe acute pancreatitis managed by operative and non operative measures. AB - AIM: Present study reports the long term functional and morphological changes following severe acute pancreatitis and compares patients managed by operative and non-operative methods. Association between morphological changes and functional parameters were studied. MATERIALS AND METHODS: 35 patients with one year of follow up after recovery from attack of acute pancreatitis were evaluated. RESULTS: Etiology was alcohol in 19, gallstones in 11 and idiopathic in 5. Fourteen patients were managed non-operatively and 21 operatively. Patients in non-operative group had a mean follow-up of 18.4 +/- 8.2 months while patients in necrosectomy group had 31.4 +/- 20.6 months. 40% patients had exocrine insufficiency (abnormal fecal fat) while 48.5% patients (17/35) had new onset diabetes. 90% patients had morphological changes in pancreas. Exocrine abnormality was significantly higher in necrosectomy group compared to non operative group (57.2% vs 14.1%, p = 0.01). Patients undergoing necrosectomy had higher incidence of endocrine dysfunction {61.9% in surgery and 28.5% in non operative group (p = 0.053)}. Operative group had more number of patients with completely non-visualized main pancreatic duct (MPD) (p = 0.028) and non operative group had significantly higher irregular MPD (p = 0.021). Exocrine dysfunction was more in patients with complete non-visualization of MPD and/or incompletely visualized MPD (p = 0.013). CONCLUSION: Patients managed non operatively had significantly less exocrine and endocrine dysfunction compared to operated patients. Exocrine dysfunction was significantly associated with complete non-visualization of MPD and/or incompletely visualized MPD. PMID- 26364169 TI - [Sociodemographic and Clinical Characteristics of Transsexual Individuals who Applied to a Psychiatry Clinic for Sex Reassignment Surgery]. AB - OBJECTIVE: The aim of the study was to investigate sociodemographic and clinical characteristics of people with gender dysphoria and differences of sociodemographic and clinical characteristics between female-to-male (FtM) and male-to-female (MtF) transsexual individuals. METHOD: This study examined retrospectively sociodemographic and clinical characteristics of 139 cases with the diagnosis of gender dysphoria who were willing to undergo sex reassignment surgery and were referred to the Cerrahpasa Medical Faculty between 2007-2013. RESULTS: Among 139 patients with gender dysphoria 102 were MtF (73,4%), and 37 patients were FtM (26,6%). In MtFs, rates of working in jobs which do not require high education level, unemployment, being a sex worker (p < 0,001), drug use (p = 0,017), and not having the health insurance (p < 0,001) were found to be significantly higher than FtMs. Rates of receiving psychotherapy for gender dysphoria (p = 0,001) and starting hormone therapy under the supervision of a doctor (p < 0,001) were significantly higher in FtMs, however higher rates of taking hormone therapy (p < 0,001) and undergoing surgery for sex reassignment (p < 0,001) were observed in the MtFs. CONCLUSION: There are significant differences both in sociodemographic characteristics and clinical characteristics between MtFs and FtMs. However further studies would be needed to identify underlying causes. PMID- 26364170 TI - [The Relationship of the Change in Symptoms and Cognitive Functions With the Change in Cortical Inhibition Parameters Measured by Transcranial Magnetic Stimulation: An Eight-Week Follow-Up Study]. AB - OBJECTIVE: Transcranial magnetic stimulation (TMS) studies show cortical inhibition (CI) abnormalities in patients with schizophrenia. However, the relationship between the changes in CI and the changes in psychopathology and cognition caused by antipsychotic treatment is not known. This is an 8 week follow up study which aims to evaluate the relationship of the change in the symptoms and cognitive functions with the change in the CI of the patients, who are switched to new atypical antipsychotic treatment, and to compare the TMS measures of patients with those of controls. METHOD: Thirteen patients and age, sex, education matched 13 controls were included in the study. Patients were assessed with TMS, Positive and Negative Syndrome Scale (PANSS) and neurocognitive battery at baseline and 8th week, while the control group was evaluated once, with neurocognitive battery and TMS. The CI parameters studied by TMS were resting motor threshold, cortical silent period, ipsilateral silent period (ISP), short interval-intracortical inhibition (SICI) and intracortical facilitation. RESULTS: Intracortical facilitation (ICF) was weaker, ISP was longer in patients than the controls both at the baseline and at the end of the eight weeks. Intracortical facilitation decreased with 8 weeks of antipsychotic treatment indicating an increase in CI. The decrease in PANSS general psychopathology score was related positively with the decrease in ICF. SICI was related positively with cognitive test performances cross-sectionally and longitudinally. CONCLUSION: Our findings suggest that increase in CI is associated with the improvement in the symptoms and the action of the atypical antipsychotics. PMID- 26364171 TI - [The Relationship Between Emotion Recognition and the Symptoms of Attention Deficit and Impulsivity in Adult Patients With Attention Deficit Hyperactivity Disorder]. AB - PURPOSE: Interpersonal relationship disorders in adults with Attention Deficit Hyperactivity Disorder (ADHD) can be associated with the impairment of non-verbal communication. The purpose of our study was to compare the emotion recognition, facial recognition and neuropsychological assessments of adult ADHD patients with those of healthy controls, and to thus determine the effect of neuropsychological data on the recognition of emotional expressions. METHODS: This study, which was based on a case-control model, was conducted with patients diagnosed with ADHD according to the DSM-IV-TR, being followed and monitored at the adult ADHD clinic of the Psychiatry Department of the Istanbul University Istanbul Medical Faculty Hospital. The study group consisted of 40 adults (27.5% female) between the ages of 20-65 (mean age 25.96 +/- 6.07; education level: 15.02+/-2.34 years) diagnosed with ADHD, and 40 controls who were matched/similar with the study group with respect to age, gender, and education level. In the ADHD group, 14 (35%) of the patients had concomitant diseases. Pictures of Facial Affect, the Benton Face Recognition Test, and the Continuous Performance Test were used to respectively evaluate emotion recognition, facial recognition, and attention deficit and impulsivity of the patients. RESULTS: It was determined that, in comparison to the control group, the ADHD group made more mistakes in recognizing all types of emotional expressions and neutral expressions. The ADHD group also demonstrated more cognitive mistakes. Facial recognition was similar in both groups. It was determined that impulsivity had a significant effect on facial recognition. CONCLUSION: The social relationship disorders observed in ADHD can be affected by emotion recognition processes. In future studies, it may be possible to investigate the effects that early psychopharmacological and psychotherapeutic interventions administered for the main symptoms of ADHD have on the impairment of emotion recognition. PMID- 26364172 TI - [The Relationship Between Marital Adjustment and Psychological Symptoms in Women: The Mediator Roles of Coping Strategies and Gender Role Attitudes]. AB - OBJECTIVE: The aim of this study were to investigate the mediator role of coping strategies and gender roles attitudes on the relationship between women's marital adjustment and psychological symptoms. METHODS: 248 married women participated in the study. Participants completed Marital Adjustment Scale, Ways of Coping Questionnaire, Brief Symptom Inventory, Gender Role Attitudes Scale and Demographic Information Form. RESULTS: Regression analyses revealed that Submissive (Sobel z= -2.47, p<.01) and Helpless Coping Approach (Sobel z=-2.95, p<.001) have partial mediator role on the relationship between marital relationship score and psychological symptom level. Also, having Egalitarian Gender Role Attitude effects the psychological symptoms in relation with the marital relationship, but it is seen that this effect is not higher enough to play a mediator role (Sobel z =-1.21, p>.05). CONCLUSION: Regression analysis showed that there is a statistically significant correlation between women's marital adjustment and their psychological symptoms, indicating that the marital adjustment decreases as the psychological symptoms increases. It is also found out that submissive and helpless coping approach have mediator roles in this relationship. Also, contrary to expectations, having egalitarian gender role attitude effects the psychological symptoms in relation with the marital relationship, but this effect does not seem to play a mediator role. It is thought that the effects of marriage and couple therapy approaches considering couples?s problem solving and coping styles should be examined in further studies. PMID- 26364173 TI - [A Study to Determine the Norms for the Trail Making Test For the Age Range of 20 49 in Turkey]. AB - OBJECTIVE: The main goal of the study is to determine the normative values of Trail Making Test (TMT) for people between 20-49 years of age; to examine the effect of age, education and sex variables over TMT scores and identify the reliability coefficient of the test. METHOD: The sample of the study consisted of 133 women and 130 men, 261 voluntary and healthy participants in total. The data of the research was collected according to 3 x 2 x 2 factorial experimental design; and the participants were distributed to experimental conditions well balanced in terms of the levels of age, education and sex. TMT A and B form, and Beck Depression Scale (BDS) were applied for the assessment. RESULTS: Seven scores were calculated determining for Turkish normative values; 3 x 2 x 2 factorial multivariate variance analysis was applied in order to identify the effect of levels of age, education and sex over TMT scores. According to the results of the analyses, it was found that main effect of education was significant, while the main effects of age and sex variables were not (p<.05). The test-retest reliability coefficients of the TMT changed between .71 and .87. CONCLUSION: This study indicated that especially the TMT B and subtest scores were affected by the education in the range of 20-49 years of age. Additionally, normative values depending on the means of TMT scores for 20-49 age group were obtained in the study; it was shown that TMT was a reliable assessment tool. PMID- 26364174 TI - [Adaptation of the Childhood Anxiety Sensitivity Index for Use in Turkey]. AB - OBJECTIVE: Anxiety sensitivity (AS) refers to the fear of anxiety-related sensations. The aim of the present study is to investigate the validity and reliability of Childhood Anxiety Sensitivity Index (CASI) and adapting it into Turkish. METHOD: The study group consisted of 328 healthy individuals whose age between 8-15 years old. All subjects included in the study filled out the Childhood Anxiety Sensitivity Index (CASI) and the State-Trait Anxiety Inventories for Children (STAI-C). RESULTS: The CASI was found to be significantly related to both trait and state anxiety scores (r=0.42 and r=0.32, respectively). It had a high internal consistency (Cronbach a= 0.74) and good test-retest reliability (r= 0.77, p< 0.001). Explorotary factor analyses showed that the CASI is comprised of 6 lower-order factors. However, CASI subfactors was established according to literature as a three factor model: physical, cognitive and social. CONCLUSION: According to the present study, the CASI Turkish version was shown to be a valid and a reliable scale. PMID- 26364175 TI - [Ethical Evaluation of Non-Therapeutic Male Circumcision]. AB - Elective circumcision for nonmedical reasons is a surgical approach which is historically long standing and accepted as the most performed procedure. The necessity of the procedure is usually for religious and traditional reasons alongside some medical ground related benefits to enable its social acceptability. The discussion of the subject from the aspect of ethics becomes necessary as there is no consensus about the benefits or harmfulness of nonmedical circumcision. Fundamental ethical discussions about circumcision, which contradicts legal acceptance criteria of any medical application, are related to the basic concepts of the existence of an individual such as sovereignty, the loss of bodily integrity, and privacy. The recent legal processes and the fact that the European Council and the American Academy of Pediatrics have put the issue on their agenda have increased the necessity of these ethical evaluations. The responsibility of consideration and evaluation of ethical permission of every circumcision procedure, besides discussing the necessity of circumcision for improvement and protection of health rests on the shoulders of the physicians because the dignity and intellectual identity of the profession require so. PMID- 26364176 TI - [A Case of Sporadic Creutzfeldt-Jakob Disease That Developed With Psychiatric Symptoms]. AB - Creutzfeldt-Jakob disease (CJD) is a fairly rare prion sickness characterized by rapidly progressive dementia and neuropsychiatric symptoms. The diversity of clinical characteristics of the disease causes difficulties during diagnosis. The first finding of the disease might be psychiatric symptoms. The male patient who was diagnosed with CJD after dementia, ataxia, and myoclonus developed rapidly following psychiatric symptoms, was presented in order to draw attention to the onset with psychiatric symptoms in CJD. PMID- 26364177 TI - [Pregabalin Dependence: A Case Report]. AB - Pregabalin is a new generation antiepileptic that exerts its effect by decreasing the release of such neurotransmitters as glutamate, noradrenaline, and substance P. Pregabalin can be prescribed in Turkey at 150-600 mg to treat neuropathic pain, generalized anxiety disorder, and fibromyalgia, and as concomitant therapy in adult patients with partial epilepsy. Experimental studies have shown that pregabalin could be beneficial in the treatment of benzodiazepine dependence and withdrawal, as well as for relapse prevention in patients with alcohol dependence. Nonetheless, the number of case reports on the abuse potential of pregabalin has increased. Herein we present a patient with pregabalin dependence. The patient?s underlying alcohol and polysubstance dependence, and symptoms of generalized anxiety were thought to contribute to the development of pregabalin dependence. The patient reported that he had experienced severe withdrawal symptoms when he tried to stop using pregabalin. Bupropion and low-dose quetiapine were added to his paroxetine treatment, and pregabalin was discontinued gradually. Following this treatment the patient had not exhibited any signs of pregabalin dependence for one month. Although pregabalin is a promising drug for various psychiatric disorders, it should be used carefully in patients with a history of substance dependence. PMID- 26364178 TI - [Clozapine and Olanzapine Associated Atrial Fibrillation: A Case Report]. AB - OBJECTIVE: Atrial fibrillation is a serious side effect of antipsychotic drugs, it is very rare but can be fatal. In this case report, a subject who developed an atrial fibrillation after receiving clozapine and olanzapine has been presented. CASE: A 49 year-old female patient with a 10-year history of schizophrenia with no additional disease history was admitted to the hospital with the diagnosis of schizophrenia. Clozapine was started to be given as 12,5 mg/day and then it was gradually increased for the patient. After the development of atrial fibrillation when the clozapine dose was at 100 mg/day (25th day of the treatment), the patient was monitored with daily ECG and no medicine was given in this period. Then, after one week, the clozapine was started to be given as 12.5 mg/day and it was increased to a dose of 100 mg per day. Meanwhile, a single dose of 10 mg of olanzapine velotab was given to the patient with no cardiac problems to prevent agitation and atrial fibrillation developed again after that. Holter ECG was within normal limits. Clozapine treatment was discontinued when the treatment dose was 250 mg/day, because atrial fibrillation developed again. After a drug free one week, atrial fibrillation did not occur during the following haloperidol, risperidone, quetiapine treatments. CONCLUSION: It is especially very important to monitor the cardiac side-effects in the patients who are using atypical antipsyhotic drugs and ECG monitorization is equally important. More studies are needed to be made towards the research of the antipsychotic arrhythmia relationship. PMID- 26364179 TI - [Insight and Social Functioning in Deficit and Nondeficit Schizophrenia]. PMID- 26364180 TI - Effectiveness of botulinum toxin injection in the treatment of de novo OAB symptoms following midurethral sling surgery. AB - INTRODUCTION AND HYPOTHESIS: Intravesical onabotulinumtoxinA (Botox(r)) is effective for idiopathic overactive bladder (OAB) symptoms. Our primary objective was to compare the efficacy of onabotulinumtoxinA for women with de novo OAB after midurethral sling (MUS) surgery and women with idiopathic OAB. METHODS: Women enrolled in this prospective study had idiopathic (n = 53) or de novo (n = 49) OAB symptoms after MUS, with at least one episode of urgency urine incontinence per day. OnabotulinumtoxinA (100 U) was administered in 20 intradetrusor injections. Postvoid residual volumes were checked at 2, 4 and 12 weeks. Participants completed a 3-day bladder diary and the King's Health Questionnaire (KHQ) before and 12 weeks after treatment. RESULTS: After 12 weeks, 22 patients (41.5 %) in the idiopathic OAB and 19 patients (38.8 %) in the de novo OAB groups were completely dry. OnabotulinumtoxinA injections had a significant benefit within both groups (p <0.001) to decrease both the daily numbers of voids (-2.39 and -2.0) and incontinence episodes (-1.38 and -1.44), with no significant difference between groups. We observed an increase of mean voided volume of >90 ml in both groups. Urinary retention was observed in four patients. CONCLUSIONS: We observed similar improvement in OAB symptoms after intravesical onabotulinumtoxinA injections within both groups. The rates of retention and requirement for catheterization even for women with a prior MUS were acceptable. These observational data provide evidence that onabotulinumtoxinA can effectively treat patients with OAB following stress urinary incontinence surgery. PMID- 26364181 TI - Early biomarkers from dynamic contrast-enhanced magnetic resonance imaging to predict the response to antiangiogenic therapy in high-grade gliomas. AB - INTRODUCTION: The aim of this study is to investigate whether early changes in tumor volume and perfusion measurements derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) may predict response to antiangiogenic therapy in recurrent high-grade gliomas. METHODS: Twenty-seven patients who received bevacizumab every 3 weeks were enrolled in the study. For each patient, three MRI scans were performed: at baseline, after the first dose, and after the fourth dose of bevacizumab. The entire tumor volume (V(tot)), as well as contrast enhanced and noncontrast-enhanced tumor subvolumes (V(CE-T1) and V(NON-CE-T1), respectively) were outlined using post-contrast T1-weighted images as a guide for the tumor location. Histogram analysis of normalized IAUGC (nIAUGC) and transfer constant K(trans) maps were performed. Each patient was classified as a responder patient if he/she had a partial response or a stable disease or as a nonresponder patient if he/she had progressive disease. RESULTS: Responding patients showed a larger reduction in V(NON-CE-T1) after a single dose, compared to nonresponding patients. Tumor subvolumes with increased values of nIAUGC and K(trans), after a single dose, significantly differed between responders and nonresponders. The radiological response was found to be significantly associated to the clinical outcome. After a single dose, V(tot) was predictive of overall survival (OS), while V(CE-T1) showed a tendency of correlation with OS. CONCLUSION: Tumor subvolumes with increased nIAUGC and K(trans) showed the potential for improving the diagnostic accuracy of DCE. Early assessments of the entire tumor volume, including necrotic areas, may provide complementary information of tumor behavior in response to anti-VEGF therapies and is worth further investigation. PMID- 26364183 TI - [Queries related to the technology of soybean seed inoculation with Bradyrhizobium spp]. AB - With the aim of exploiting symbiotic nitrogen fixation, soybean crops are inoculated with selected strains of Bradyrhizobium japonicum, Bradyrhizobium diazoefficiens or Bradyrhizobium elkanii (collectively referred to as Bradyrhizobium spp.). The most common method of inoculation used is seed inoculation, whether performed immediately before sowing or using preinoculated seeds or pretreated seeds by the professional seed treatment. The methodology of inoculation should not only cover the seeds with living rhizobia, but must also optimize the chances of these rhizobia to infect the roots and nodulate. To this end, inoculated rhizobia must be in such an amount and condition that would allow them to overcome the competition exerted by the rhizobia of the allochthonous population of the soil, which are usually less effective for nitrogen fixation and thus dilute the effect of inoculation on yield. This optimization requires solving some queries related to the current knowledge of seed inoculation, which are addressed in this article. I conclude that the aspects that require further research are the adhesion and survival of rhizobia on seeds, the release of rhizobia once the seeds are deposited in the soil, and the movement of rhizobia from the vicinity of the seeds to the infection sites in the roots. PMID- 26364182 TI - Mapping of cerebral metabolic rate of oxygen using dynamic susceptibility contrast and blood oxygen level dependent MR imaging in acute ischemic stroke. AB - INTRODUCTION: MR-derived cerebral metabolic rate of oxygen utilization (CMRO(2)) has been suggested to be analogous to PET-derived CMRO(2) and therefore may be used for detection of viable tissue at risk for infarction. The purpose of this study was to evaluate MR-derived CMRO(2) mapping in acute ischemic stroke in relation to established diffusion- and perfusion-weighted imaging. METHODS: In 23 patients (mean age 63 +/- 18.7 years, 11 women) with imaging findings for acute ischemic stroke, relative oxygen extraction fraction was calculated from quantitative transverse relaxation times (T2, T2*) and relative cerebral blood volume using a quantitative blood oxygenation level dependent (BOLD) approach in order to detect a local increase of deoxyhemoglobin. Relative CMRO(2) (rCMRO(2)) maps were calculated by multiplying relative oxygen extraction fraction (rOEF) by cerebral blood flow, derived from PWI. After co-registration, rCMRO(2) maps were evaluated in comparison with apparent diffusion coefficient (ADC) and time-to peak (TTP) maps. Mean rCMRO(2) values in areas with diffusion-restriction or TTP/ADC mismatch were compared with rCMRO(2) values in the contralateral tissue. RESULTS: In tissue with diffusion restriction, mean rCMRO(2) values were significantly decreased compared to perfusion-impaired (17.9 [95 % confidence interval 10.3, 25.0] vs. 58.1 [95 % confidence interval 50.1, 70.3]; P < 0.001) and tissue in the contralateral hemisphere (68.2 [95 % confidence interval 61.4, 75.0]; P < 0.001). rCMRO(2) in perfusion-impaired tissue showed no significant change compared to tissue in the contralateral hemisphere (58.1 [95 % confidence interval 50.1, 70.3] vs. 66.7 [95 % confidence interval 53.4, 73.4]; P = 0.34). CONCLUSION: MR-derived CMRO(2) was decreased within diffusion-restricted tissue and stable within perfusion-impaired tissue, suggesting that this technique may be adequate to reveal different pathophysiological stages in acute stroke. PMID- 26364184 TI - The fungus Nomuraea rileyi growing on dead larvae of Anticarsia gemmatalis associated with soybean plants (Glycine max) in Esperanza (Argentina). PMID- 26364185 TI - [Yeast irrigation enhances the nutritional content in hydroponic green maize fodder]. AB - The objective of this study was to evaluate the effect of irrigation with yeasts (Debaryomyces hansenii var. Fabry, Yarowia lipolytica YIBCS002, Yarowia lipolytica var. BCS and Candida pseudointermedia) on the final nutritional content of hydroponic green maize fodder (Zea Zea mays L.), applied at different fodder growth stages (1. seed-seedling stage, 2. seedling-plant 20cm, 3. during all the culture). Irrespective of the fodder growth stages at which they were applied, all yeasts tested enhanced the content of raw protein, lipids, ash, moisture and energy. The percentage of electrolytes (Na, K, Cl, sulphates, Ca and Mg) showed different responses depending on the kind of yeast applied; D. hansenii exhibited the highest increment in all electrolytes, except for phosphorous. We conclude that the addition of yeasts belonging to the genera Debaryomyces, Candida and Yarowia to the irrigation solution of hydroponic systems enhances the nutrient content of green fodder. This kind of irrigation can be applied to generate high commercial value cultures in limited spaces. PMID- 26364186 TI - Impact of hydroquinone used as a redox effector model on potential denitrification, microbial activity and redox condition of a cultivable soil. AB - In this microcosm study, we analyzed the effect produced by hydroquinone on the expression of soil biological denitrification, in relation to the redox state of the soil, both in terms of intensity factor (Eh') and capacity factor (amount of oxidized or reduced compounds). The supplementation of an Argiudoll soil with hydroquinone decreased the soil apparent reduction potential (Eh') and soil dehydrogenase activity (formazan production from tetrazolium chloride reduction; redox capacity factor), the relationship between both factors being highly significative, r=0.99 (p<0.001). The bacterial population (measured by colony forming units) increased, and the production of N2O was greater (p<0.001) at 200 and 400MUg/g dry soil doses. Furthermore, there was an inverse relationship between soil dehydrogenase activity and the number of bacteria (r=-0.82; p<0.05), increased denitrification activity and changes in the CO2/N2O ratio value. These results suggest that hydroquinone at supplemented doses modified the soil redox state and the functional structure of the microbial population. Acetate supplementation on soil with hydroquinone, to ensure the availability of an energy source for microbial development, confirmed the tendency of the results obtained with the supplementation of hydroquinone alone. The differences observed at increased doses of hydroquinone might be explained by differences on the hydroquinone redox species between treatments. PMID- 26364187 TI - [Microorganisms conferring beneficial health effects]. PMID- 26364188 TI - EDTA Chelation Therapy to Reduce Cardiovascular Events in Persons with Diabetes. AB - The Trial to Assess Chelation Therapy (TACT) was a randomized double-blind placebo-controlled trial enrolling patients age >=50 years with prior myocardial infarction. TACT used a 2 * 2 factorial design to study ethylene diamine tetraacetic acid (EDTA) chelation and high-dose vitamin supplementation. Chelation provided a modest but significant reduction in cardiovascular endpoints. The benefit was stronger and significant among participants with diabetes but absent in those without diabetes. Mechanisms by which chelation might reduce cardiovascular risk in persons with diabetes include the effects of EDTA chelation on transition and toxic metals. Transition metals, particularly copper and iron, play important roles in oxidative stress pathways. Toxic metals, in particular cadmium and lead, are toxic for the cardiovascular system. This review discusses the epidemiologic evidence and animal and human studies supporting the role of these metals in the development of diabetes and ischemic heart disease and potential ways by which EDTA chelation could confer cardiovascular benefit. PMID- 26364189 TI - Sub-Inhibitory Concentration of Piperacillin-Tazobactam May be Related to Virulence Properties of Filamentous Escherichia coli. AB - Sub-inhibitory concentrations of antibiotics are always generated as a consequence of antimicrobial therapy and the effects of such residual products in bacterial morphology are well documented, especially the filamentation generated by beta-lactams. The aim of this study was to investigate some morphological and pathological aspects (virulence factors) of Escherichia coli cultivated under half-minimum inhibitory concentration (1.0 ug/mL) of piperacillin-tazobactam (PTZ sub-MIC). PTZ sub-MIC promoted noticeable changes in the bacterial cells which reach the peak of morphological alterations (filamentation) and complexity at 16 h of antimicrobial exposure. Thereafter the filamentous cells and a control one, not treated with PTZ, were comparatively tested for growth curve; biochemical profile; oxidative stress tolerance; biofilm production and cell hydrophobicity; motility and pathogenicity in vivo. PTZ sub-MIC attenuated the E. coli growth rate, but without changes in carbohydrate fermentation or in traditional biochemical tests. Overall, the treatment of E. coli with sub-MIC of PTZ generated filamentous forms which were accompanied by the inhibition of virulence factors such as the oxidative stress response, biofilm formation, cell surface hydrophobicity, and motility. These results are consistent with the reduced pathogenicity observed for the filamentous E. coli in the murine model of intra abdominal infection. In other words, the treatment of E. coli with sub-MIC of PTZ suggests a decrease in their virulence. PMID- 26364191 TI - Larval Habitats Diversity and Distribution of the Mosquito (Diptera: Culicidae) Species in the Republic of Moldova. AB - A countrywide field survey of immature mosquitoes was conducted in Moldova with the aim to evaluate the Culicidae species composition in different larval habitats and their distribution in the country. In total, 259 potential larval habitats were sampled in the 53 localities, resulting in 9,456 specimens. Twenty species belonging to the genera Anopheles, Aedes, Culex, Culiseta, and Uranotaenia were collected. Mean species richness in aquatic habitats ranged from 1.00 to 4.00, and, for example, was higher in swamps, flood plains, ditches, and large ground pools and lower in rivers, streams, tree-holes, and containers. Six mosquito species were identified only in a single type of aquatic habitat. Anopheles maculipennis s.l., Culex pipiens pipiens L., and Culex modestus Ficalbi were the most abundant and distributed species representing over 80% of the identified specimens. Three, four, and five associated species were recorded from 23.5% of mosquito-positive aquatic habitats. Our findings demonstrate the co occurrence of Cx. p. pipiens and Culex torrentium Martini in natural and rural environments. It is concluded that the study area has undergone a dramatic ecological change since the previous studies in the 1950s, causing the near extinction of Culex theileri Theobald from Moldova. An. maculipennis s.l. larval abundance, reduced by the DDT control of the adults in the 1950s, had returned to those of the 1940s. Restoration of An. maculipennis s.l. abundance in combination with imported malaria cases constitute a risk of the reintroduction of malaria transmission in Moldova. PMID- 26364190 TI - The relationship between smoking and quality of life in advanced lung cancer patients: a prospective longitudinal study. AB - PURPOSE: Smoking is a major cause of lung cancer, and continued smoking may compromise treatment efficacy and quality of life (health-related quality of life (HRQoL)) in patients with advanced lung cancer. Our aims were to determine (i) preference for treatments which promote quality over length of life depending on smoking status, (ii) the relationship between HRQoL and smoking status at diagnosis (T1), after controlling for demographic and clinical variables, and (iii) changes in HRQoL 6 months after diagnosis (T2) depending on smoking status. METHODS: Two hundred ninety-six patients with advanced lung cancer were given questionnaires to assess HRQoL (EORTC QLQ-C30), time-trade-off for life quality versus quantity (QQQ) and smoking history (current, former or never smoker) at diagnosis (T1) and 6 months later (T2). Medical data were extracted from case records. RESULTS: Questionnaires were returned by 202 (68.2 %) patients at T1 and 114 (53.3 %) at T2. Patients favoured treatments that would enhance quality of life over increased longevity. Those who continued smoking after diagnosis reported worse HRQoL than former smokers or those who never smoked. Smoking status was a significant independent predictor of coughing in T1 (worse in smokers) and cognitive functioning in T2 (better in never smokers). CONCLUSIONS: Smoking by patients with advanced lung cancer is associated with worse symptoms on diagnosis and poorer HRQoL for those who continue smoking. The results have implications to help staff explain the consequences of smoking to patients. PMID- 26364192 TI - Starmera pilosocereana sp. nov., a yeast isolated from necrotic tissue of cacti in a sandy coastal dune ecosystem. AB - Two strains of a novel cactophilic yeast species were isolated from the columnar cactus Pilosocereus arrabidae in a sand dune ecosystem in Rio de Janeiro, Brazil. Phylogenetic analysis of sequences of the large subunit rRNA gene D1/D2 domains showed that the strains represent a sister species to Starmera caribaea, from which it differs by 21 nt substitutions and two indels. The novel species is heterothallic and the asci are deliquescent with the formation of two to four hat shaped ascospores. The name Starmera pilosocereana sp. nov. is proposed for the species. The type strain is UFMG-CM-Y316T ( = CBS 13266T) and the allotype is UFMG-CM-Y346a ( = CBS 13265). The Mycobank number is MB 810683. In addition, Candida stellimalicola belonging to the Starmera clade, is reassigned to Starmera as a new combination. PMID- 26364193 TI - Propofol and non-propofol based sedation for outpatient colonoscopy-prospective comparison of depth of sedation using an EEG based SEDLine monitor. AB - Propofol is a popular anesthetic sedative employed in colonoscopy. It is known to increase the patient satisfaction and improve throughput. However, there are concerns among the clinicians with regard to the depth of sedation, as a deeper degree of sedation is known to increase the incidence of aspiration and other adverse events. So we planned to compare the depth of sedation between propofol and non-propofol based sedation in patients undergoing outpatient colonoscopy, as measured by an electroencephalogram (EEG) based monitor SEDLine monitor (SedlineInc., San Diego, CA). The non-randomized prospective observational study was performed in the outpatient gastroenterology suite of the Hospital of the University of Pennsylvania, Philadelphia. Patients included ASA class I-III aged more than 18 years scheduled for colonoscopy under Propofol or non-propofol based sedation. After an institutional review board approval, a written consent was obtained from prospective patients. Sedation (propofol or non-propofol based) was administered by either a certified nurse anesthetist under the supervision of an anesthesiologist (propofol) or a registered endoscopy nurse under the guidance of the endoscopist performing the procedure (non-propofol sedation). Depth of sedation was measured with an EEG based SEDLine monitor. The sedation providers were blinded to the patient state index-the indicator of depth of sedation. PSI (patient state index-SEDLine reading) was documented at colonoscope insertion, removal and at the return of verbal responsiveness after colonoscope withdrawal. Sedation spectrum was retrieved from the data stored on the SEDLine monitor. Patients sedated with propofol experience significantly deeper degrees of sedation at all times during the procedure. Additionally, during significant part of the procedure, they are at PSI levels associated with deep general anesthesia. The group that received propofol was more deeply sedated and had lower PSI values. Lighter propofol titration protocols may lead to improved patient care such as lowering risk of aspiration and hypotension. The role of processed EEG monitors such as the SEDLine monitor to improve sedation protocols remains to be determined. Trial registration We obtained an ethical clearance from the Institute. No trial registration was mandated, as no interventional drug or investigational device were used during the study. PMID- 26364194 TI - Suitability of different growth substrates as source of nitrogen for sulfate reducing bacteria. AB - Sulfate reducing bacteria (SRB) mediated treatment of acid mine drainage is considered as a globally accepted technology. However, inadequate information on the role of nitrogen source in the augmentation of SRB significantly affects the overall treatment process. Sustenance of SRB depends on suitable nitrogen source which is considered as an important nutrient. This review focuses on the different nitrogen rich growth substrates for their effectiveness to support SRB growth and sulfate reduction in passive bioreactors. Compounds like NH4Cl, NH4HCO3, NO3 (-), aniline, tri-nitrotoluene, cornsteep liquor, peptone, urea, and chitin are reported to have served as nitrogen source for SRB. In association with fermentative bacteria, SRB can metabolize these complex compounds to NH4 (+), amines, and amino acids. After incorporation into cells, these compounds take part in the biosynthesis of nucleic acids, amino acids and enzyme co-factor. This work describes the status of current and the probable directions of the future research. PMID- 26364195 TI - Efficacy and safety of tenofovir in nucleos(t)ide-naive patients with genotype C chronic hepatitis B in real-life practice. AB - BACKGROUND: Tenofovir disoproxil fumarate (TDF) has demonstrated potent antiviral activity against hepatitis B virus (HBV) in clinical trials. Although its efficacy has been demonstrated in Caucasian populations, TDF has not previously been studied in Korean patients who present the predominance of HBV genotype C and of vertical or perinatal transmission. OBJECTIVE: The aim of this study was to evaluate the efficacy of TDF in Korean chronic hepatitis B (CHB) patients in real-life practice, and to determine the clinical variables that contribute to virologic response. SETTING: Large academic medical center in Korea. METHOD: We retrospectively investigated the efficacy of TDF treatment for more than 6 months in 151 nucleos(t)ide-naive CHB patients. MAIN OUTCOME MEASURE: The primary endpoint was a virologic response (VR), defined as an HBV DNA level of <12 IU/mL. Secondary endpoints were rates of alanine aminotransaminase (ALT) normalization, hepatitis B e antigen (HBeAg) seroconversion, virologic breakthrough, and safety. RESULTS: All patients were the genotype C2. The median duration of TDF treatment was 13 months (range 7-18 months). Ninety-two (61.0 %) patients were HBeAg positive. The mean pre-treatment HBV DNA level was 6.34 +/- 1.42 log10 IU/mL. Among the 131 patients with elevated ALT levels at baseline, 128 (97.7 %) patients achieved ALT normalization during TDF treatment. VR was achieved in 97 (64.2 %) patients. The cumulative rates of VR at 6, 9, 12, and 18 months were 47.0, 59.4, 67.9, and 69.3 %, respectively. Among the 92 HBeAg-positive patients, 14 (15.2 %) patients achieved HBeAg seroconversion. In multivariate analysis, absolute HBV DNA levels at baseline (P < 0.001; OR 0.529; 95 % CI 0.560-0.744) and HBeAg positivity (P = 0.015; OR 0.731; 95 % CI 0.615-0.869) were significantly associated with VR. Virologic breakthrough was observed in four patients. These four patients had poor adherence to TDF. Most of the adverse events were mild in severity. No significant changes were observed in serum creatinine and phosphorus levels. CONCLUSIONS: TDF was effective and well tolerated in Korean genotype C CHB patients in real life practice, consistent with larger registration trials. The absolute HBV DNA levels at baseline and HBeAg positivity were significantly associated with VR. PMID- 26364196 TI - Factors related to the provision of home-based end-of-life care among home-care nursing, home help, and care management agencies in Japan. AB - BACKGROUND: To promote home death, it is necessary to clarify the institutional barriers to conducting end-of-life (EOL) care and consider strategies to deal with this process. This study aims to clarify institution-related factors associated with the provision of home-based EOL care cases, and to compare them among three different types of home-care agencies. METHODS: We administered a cross-sectional survey throughout Japan to investigate the number and characteristics of EOL cases of home-care nursing (HN), home-help (HH) and care management (CM) agencies. Bivariate and multivariate analyses were performed for each type of agency to examine factors related to the provision of EOL care. RESULTS: 378 HN agencies, 274 HH agencies, and 452 CM agencies responded to the distributed questionnaire. HN agencies had on average 2.1 (SD = 4.0; range 0-60) home-based EOL cases in the last 3 months, while HH agencies had 0.9 (SD = 1.3; range 0-7) and CM agencies had 1.5 (SD = 2.2; range 0-18) in the last 6 months. In a multivariable analysis of HN agencies, a large number of staff (OR: 1.52; p < 0.001) and a large number of collaborating CM agencies (OR: 1.08; p = 0.008) were positively associated with the provision of EOL care; in HH agencies, accepting EOL clients in the agency (OR: 3.29; p < 0.001) was positively associated with the provision of EOL care; in CM agencies, the number of staff (OR: 1.21; p = 0.037), the number of collaborating HH agencies (OR: 1.07; p = 0.032), and whether home-care nurses and home helpers visit clients together (OR: 1.89; p = 0.007) were positively associated with the provision of EOL care. CONCLUSION: The agency's size and the inter-agency collaborative system seemed most important among HN agencies and CM agencies, while institutional preparedness for EOL was most important for HH agencies. These findings represent important new information for targeting different effective strategies in the promotion of home-based EOL care, depending on the agency type. PMID- 26364197 TI - Is it worth carrying out determination of N-butane in postmortem samples? A case report and a comprehensive review of the literature. AB - The aim of this article is to illustrate the importance of N-butane determination in postmortem samples through a case report and to propose actions and precautions to be taken into consideration when butane is suspected to be involved in cases of death. The case concerns a 15-year-old boy found dead after sniffing a cigarette lighter refill. Toxicological investigation revealed the presence of butane in the heart and femoral blood (1280 and 1170 MUg/L, respectively), in the gastric contents (326 MUg/L), and in the liver (1010 MUg/kg) and lung tissues (210 MUg/kg). Propane was present only in the blood samples at concentrations tenfolds lower.Butane can be involved in three kinds of fatalities: deliberate inhalations including volatile substance abuse (VSA), involuntary exposure, and homicides. A fatal outcome of butane inhalation can be caused by asphyxia and/or cardiac arrhythmia. In the context where butane exposure is evidenced by non-toxicological investigations, the usefulness of the determination of butane in postmortem samples is often questionable. However, it is admitted that butane-related deaths are generally underreported. Several difficulties including sample handling and storage, substantial variation in tissue concentrations, and lack of a lethal threshold make the interpretation of butane results challenging. In our opinion, systematic toxicological methods should be developed in order to analyze butane, at least when it concerns a typical VSA victim, even when butane is not actually suspected to be the cause of death. PMID- 26364198 TI - Discovery of novel drug targets and their functions using phenotypic screening of natural products. AB - Natural products are valuable resources that provide a variety of bioactive compounds and natural pharmacophores in modern drug discovery. Discovery of biologically active natural products and unraveling their target proteins to understand their mode of action have always been critical hurdles for their development into clinical drugs. For effective discovery and development of bioactive natural products into novel therapeutic drugs, comprehensive screening and identification of target proteins are indispensable. In this review, a systematic approach to understanding the mode of action of natural products isolated using phenotypic screening involving chemical proteomics-based target identification is introduced. This review highlights three natural products recently discovered via phenotypic screening, namely glucopiericidin A, ecumicin, and terpestacin, as representative case studies to revisit the pivotal role of natural products as powerful tools in discovering the novel functions and druggability of targets in biological systems and pathological diseases of interest. PMID- 26364199 TI - Development of engineered Escherichia coli whole-cell biocatalysts for high-level conversion of L-lysine into cadaverine. AB - A whole-cell biocatalytic system for the production of cadaverine from L-lysine has been developed. Among the investigated lysine decarboxylases from different microorganisms, Escherichia coli LdcC showed the best performance on cadaverine synthesis when E. coli XL1-Blue was used as the host strain. Six different strains of E. coli expressing E. coli LdcC were investigated and recombinant E. coli XL1-Blue, BL21(DE3) and W were chosen for further investigation since they showed higher conversion yield of lysine into cadaverine. The effects of substrate pH, substrate concentrations, buffering conditions, and biocatalyst concentrations have been investigated. Finally, recombinant E. coli XL1-Blue concentrated to an OD(600) of 50, converted 192.6 g/L (1317 mM) of crude lysine solution, obtained from an actual lysine manufacturing process, to 133.7 g/L (1308 mM) of cadaverine with a molar yield of 99.90 %. The whole-cell biocatalytic system described herein is expected to be applicable to the development of industrial bionylon production process. PMID- 26364201 TI - Human Identification Using Compressed ECG Signals. AB - As a result of the increased demand for improved life styles and the increment of senior citizens over the age of 65, new home care services are demanded. Simultaneously, the medical sector is increasingly becoming the new target of cybercriminals due the potential value of users' medical information. The use of biometrics seems an effective tool as a deterrent for many of such attacks. In this paper, we propose the use of electrocardiograms (ECGs) for the identification of individuals. For instance, for a telecare service, a user could be authenticated using the information extracted from her ECG signal. The majority of ECG-based biometrics systems extract information (fiducial features) from the characteristics points of an ECG wave. In this article, we propose the use of non-fiducial features via the Hadamard Transform (HT). We show how the use of highly compressed signals (only 24 coefficients of HT) is enough to unequivocally identify individuals with a high performance (classification accuracy of 0.97 and with identification system errors in the order of 10(-2)). PMID- 26364203 TI - JNCC guidelines for minimising the risk of injury and disturbance to marine mammals from seismic surveys: We can do better. AB - The U.K.'s Joint Nature Conservation Committee 1998 guidelines for minimising acoustic impacts from seismic surveys on marine mammals were the first of their kind. Covering both planning and operations, they included various measures for reducing the potential for damaging hearing - an appropriate focus at the time. Since introduction, the guidelines have been criticised for, among other things: the arbitrarily-sized safety zones; the lack of shut-down provisions; the use of mitigation measures that introduce more noise into the environment (e.g., soft starts); inadequate observer training; and the lack of standardised data collection protocols. Despite the concerns, the guidelines have remained largely unchanged. Moreover, increasing scientific recognition of the scope and magnitude of non-injurious impacts of sound on marine life has become much more widespread since the last revisions in 2010. Accordingly, here we present feasible and realistic recommendations for such improvements, in light of the current state of knowledge. PMID- 26364202 TI - Toward a Fault Tolerant Architecture for Vital Medical-Based Wearable Computing. AB - Advancements in computers and electronic technologies have led to the emergence of a new generation of efficient small intelligent systems. The products of such technologies might include Smartphones and wearable devices, which have attracted the attention of medical applications. These products are used less in critical medical applications because of their resource constraint and failure sensitivity. This is due to the fact that without safety considerations, small integrated hardware will endanger patients' lives. Therefore, proposing some principals is required to construct wearable systems in healthcare so that the existing concerns are dealt with. Accordingly, this paper proposes an architecture for constructing wearable systems in critical medical applications. The proposed architecture is a three-tier one, supporting data flow from body sensors to cloud. The tiers of this architecture include wearable computers, mobile computing, and mobile cloud computing. One of the features of this architecture is its high possible fault tolerance due to the nature of its components. Moreover, the required protocols are presented to coordinate the components of this architecture. Finally, the reliability of this architecture is assessed by simulating the architecture and its components, and other aspects of the proposed architecture are discussed. PMID- 26364204 TI - Evaluation for coastal reclamation feasibility using a comprehensive hydrodynamic framework: A case study in Haizhou Bay. AB - Coastal reclamation (CR) is a prevailing approach to solve the contradiction between the land shortage and the growing demand of living space for human beings. In general, environmental impact assessment (EIA) focuses on evaluating the feasibility of individual coastal reclamation project (CRP). However, few studies have investigated the cumulative effect of multiple CRPs on surrounding environment. In this study, an integrated framework based on coastal hydrodynamics was established, and then applied to the feasibility evaluation of multiple CRPs for future coastal management in Haizhou Bay, China. The results indicated that three out of five reclamation projects were feasible and the remaining two were forbidden in the study area, whereas EIA approves of all the CRPs. It provides a scientific reference for effective management of coastal reclamation and future environmental impact researches when new CRPs are proposed. PMID- 26364200 TI - Genetic manipulation of secondary metabolite biosynthesis for improved production in Streptomyces and other actinomycetes. AB - Actinomycetes continue to be important sources for the discovery of secondary metabolites for applications in human medicine, animal health, and crop protection. With the maturation of actinomycete genome mining as a robust approach to identify new and novel cryptic secondary metabolite gene clusters, it is critical to continue developing methods to activate and enhance secondary metabolite biosynthesis for discovery, development, and large-scale manufacturing. This review covers recent reports on promising new approaches and further validations or technical improvements of existing approaches to strain improvement applicable to a wide range of Streptomyces species and other actinomycetes. PMID- 26364205 TI - Transport of dissolved gas and its ecological impact after a gas release from deepwater. AB - Previous models on simulating gas releases in deepwater were not focused on the dissolved component and its impact on water quality. This paper presents a new model developed for simulating the transport/spread of dissolved methane from an underwater release and its impact on dissolved oxygen in ambient water. Methane dissolves into ambient water from gas phase, direct from hydrate phase, and from dissociating hydrates formed earlier. Dissolved methane affects the dissolved oxygen levels in ambient water due to microbial interaction and possible direct absorption of oxygen into methane bubbles. We use new model simulations of Deepspill field experiments to compare with instantaneous profiles which were unpublished until now. The comparisons are very good with a short time lag, but are within the acceptable discrepancy for models for emergency response and contingency planning. Scenario simulations show the effect on dissolved oxygen due to different methane release situations. PMID- 26364206 TI - Genome instability biomarkers and blood micronutrient risk profiles associated with mild cognitive impairment and Alzheimer's disease. AB - Successful maintenance of metabolic systems relating to accurate DNA replication and repair is critical for optimal lifelong human health. Should this homeostatic balance become impaired, genomic instability events can arise, compromising the integrity of the genome, which may result in gene expression and human disease. Both genome instability and micronutrient imbalance have been identified and implicated in diseases associated with accelerated ageing which potentially leads to an increased risk for the future development of clinically defined neurodegenerative disorders. Cognitive decline leading to the clinical diagnosis of mild cognitive impairment (MCI) has been shown to predict an increased risk in later life of developing Alzheimer's disease (AD). Knowledge on the impact of dietary factors in relation to MCI and AD risk is improving but incomplete; in particular the role of nutrient combinations (i.e. nutriomes) has not been thoroughly investigated. Currently, there is a need for preventative strategies as well as the identification of robust and reproducible diagnostic biomarkers that will allow identification of those individuals with increased risk for neurodegenerative diseases. Growing evidence suggests cells originating from different somatic tissues derived from individuals that have been clinically diagnosed with neurodegenerative disorders exhibit elevated frequencies of DNA damage compared to tissues of cognitively normal individuals which could be due to malnutrition. The objective of this review is to discuss current evidence and identify knowledge gaps relating to genome instability biomarkers and blood micronutrient profiles from human studies of MCI and AD that may be specific to and contribute to the increased risk of these diseases. This is a vital step in order to create research strategies for the future development of diagnostics that are indicative of dementia risk and to inform preventative therapies. PMID- 26364207 TI - Assessment of DNA damage and mRNA/miRNA transcriptional expression profiles in hyperglycemic versus non-hyperglycemic patients with type 2 diabetes mellitus. AB - The development of type 2 diabetes mellitus (T2D) is associated with a number of genetic and environmental factors. Hyperglycemia, a T2D hallmark, is related to several metabolic complications, comorbidities and increased DNA damage. However, the molecular alterations of a proper glucose control are still unclarified. In this study, we aimed to evaluate DNA damage (comet assay), as well as to compare the transcriptional expression (mRNA and miRNA analyzed by the microarray technique) displayed by peripheral blood mononuclear cells (PBMCs) from three distinct groups: hyperglycemic T2D patients (T2D-H, n=14), non-hyperglycemic T2D patients (T2D-N, n=15), and healthy non-diabetic individuals (n=16). The comet assay revealed significantly (p<0.05) higher levels of DNA damage in T2D-H group compared to both T2D-N and control groups, while a significant difference was not observed between the control and T2D-N groups. After bioinformatics analysis, the differentially expressed mRNAs were subjected to functional enrichment analysis (DAVID) and inflammatory response was among the enriched terms found when comparing T2D-N with controls and T2D-H with T2D-N. Concerning the gene set enrichment and gene set analyses, among the differentially expressed gene sets, three were of interest: regulation of DNA repair (T2D-H versus T2D-N), superoxide response (T2D-H versus control group), and response to endoplasmic reticulum stress (T2D-H versus control group). We also identified miRNAs related with T2D and hyperglycemia not yet associated with these conditions in the literature. Some of the differentially expressed mRNAs were among the predicted targets of the differentially expressed miRNAs. Our results showed the association of hyperglycemia with increased DNA damage and aberrant expression of miRNAs and genes related to several biological processes, such as inflammation, DNA repair, ROS production and antioxidant defense, highlighting the importance of proper glycemic control. Moreover, the transcriptional expression of miRNAs provided novel information for understanding the regulatory mechanisms involved in the T2D progression. PMID- 26364209 TI - Tracing delays in infection control measures in a nosocomial norovirus outbreak. PMID- 26364208 TI - Bare below the elbows: was the target the white coat? PMID- 26364210 TI - The inaugural Healthcare Infection Society Middle East Summit: 'No action today. No cure tomorrow.'. PMID- 26364212 TI - Erratum to: Phylogenetic characterization and promoter expression analysis of a novel hybrid protein disulfide isomerase/cargo receptor subfamily unique to plants and chromalveolates. PMID- 26364211 TI - Alleviating neuropathic pain mechanical allodynia by increasing Cdh1 in the anterior cingulate cortex. AB - BACKGROUND: Plastic changes in the anterior cingulate cortex (ACC) are critical in the pathogenesis of pain hypersensitivity caused by injury to peripheral nerves. Cdh1, a co-activator subunit of anaphase-promoting complex/cyclosome (APC/C) regulates synaptic differentiation and transmission. Based on this, we hypothesised that the APC/C-Cdh1 played an important role in long-term plastic changes induced by neuropathic pain in ACC. RESULTS: We employed spared nerve injury (SNI) model in rat and found Cdh1 protein level in the ACC was down regulated 3, 7 and 14 days after SNI surgery. We detected increase in c-Fos expression, numerical increase of organelles, swollen myelinated fibre and axon collapse of neuronal cells in the ACC of SNI rat. Additionally, AMPA receptor GluR1 subunit protein level was up-regulated on the membrane through a pathway that involves EphA4 mediated by APC/C-Cdh1, 3 and 7 days after SNI surgery. To confirm the effect of Cdh1 in neuropathic pain, Cdh1-expressing lentivirus was injected into the ACC of SNI rat. Intra-ACC treatment with Cdh1-expressing lentivirus vectors elevated Cdh1 levels, erased synaptic strengthening, as well as alleviating established mechanical allodynia in SNI rats. We also found Cdh1 expressing lentivirus normalised SNI-induced redistribution of AMPA receptor GluR1 subunit in ACC by regulating AMPA receptor trafficking. CONCLUSIONS: These results provide evidence that Cdh1 in ACC synapses may offer a novel therapeutic strategy for treating chronic neuropathic pain. PMID- 26364213 TI - Analyzing the Publish-or-Perish Paradigm with Game Theory: The Prisoner's Dilemma and a Possible Escape. AB - The publish-or-perish paradigm is a prevailing facet of science. We apply game theory to show that, under rather weak assumptions, this publication scenario takes the form of a prisoner's dilemma, which constitutes a substantial obstacle to beneficial delayed publication of more complete results. One way of avoiding this obstacle while allowing researchers to establish priority of discoveries would be an updated "pli cachete", a sealed envelope concept from the 1700s. We describe institutional rules that could additionally favour high-quality work and publications and provide examples of such policies that are already in place. Our analysis should be extended to other publication scenarios and the role of other stakeholders such as scientific journals or sponsors. PMID- 26364214 TI - Reversible Experiments: Putting Geological Disposal to the Test. AB - Conceiving of nuclear energy as a social experiment gives rise to the question of what to do when the experiment is no longer responsible or desirable. To be able to appropriately respond to such a situation, the nuclear energy technology in question should be reversible, i.e. it must be possible to stop its further development and implementation in society, and it must be possible to undo its undesirable consequences. This paper explores these two conditions by applying them to geological disposal of high-level radioactive waste (GD). Despite the fact that considerations of reversibility and retrievability have received increased attention in GD, the analysis in this paper concludes that GD cannot be considered reversible. Firstly, it would be difficult to stop its further development and implementation, since its historical development has led to a point where GD is significantly locked-in. Secondly, the strategy it employs for undoing undesirable consequences is less-than-ideal: it relies on containment of severely radiotoxic waste rather than attempting to eliminate this waste or its radioactivity. And while it may currently be technologically impossible to turn high-level waste into benign substances, GD's containment strategy makes it difficult to eliminate this waste's radioactivity when the possibility would arise. In all, GD should be critically reconsidered if the inclusion of reversibility considerations in radioactive waste management has indeed become as important as is sometimes claimed. PMID- 26364215 TI - An evaluation of indirubin analogues as phosphorylase kinase inhibitors. AB - Phosphorylase kinase (PhK) has been linked with a number of conditions such as glycogen storage diseases, psoriasis, type 2 diabetes and more recently, cancer (Camus et al., 2012 [6]). However, with few reported structural studies on PhK inhibitors, this hinders a structure based drug design approach. In this study, the inhibitory potential of 38 indirubin analogues have been investigated. 11 of these ligands had IC50 values in the range 0.170-0.360MUM, with indirubin-3' acetoxime (1c) the most potent. 7-Bromoindirubin-3'-oxime (13b), an antitumor compound which induces caspase-independent cell-death (Ribas et al., 2006 [20]) is revealed as a specific inhibitor of PhK (IC50=1.8MUM). Binding assay experiments performed using both PhK-holo and PhK-gammatrnc confirmed the inhibitory effects to arise from binding at the kinase domain (gamma subunit). High level computations using QM/MM-PBSA binding free energy calculations were in good agreement with experimental binding data, as determined using statistical analysis, and support binding at the ATP-binding site. The value of a QM description for the binding of halogenated ligands exhibiting sigma-hole effects is highlighted. A new statistical metric, the 'sum of the modified logarithm of ranks' (SMLR), has been defined which measures performance of a model for both the "early recognition" (ranking earlier/higher) of active compounds and their relative ordering by potency. Through a detailed structure activity relationship analysis considering other kinases (CDK2, CDK5 and GSK-3alpha/beta), 6'(Z) and 7(L) indirubin substitutions have been identified to achieve selective PhK inhibition. The key PhK binding site residues involved can also be targeted using other ligand scaffolds in future work. PMID- 26364216 TI - Effects of fish oil replacement by vegetable oil blend on digestive enzymes and tissue histomorphology of European sea bass (Dicentrarchus labrax) juveniles. AB - The impact of replacing circa 70% fish oil (FO) by a vegetable oil (VO) blend (rapeseed, linseed, palm oils; 20:50:30) in diets for European sea bass juveniles (IBW 96 +/- 0.8 g) was evaluated in terms of activities of digestive enzymes (amylase, lipase, alkaline phosphatase, trypsin and total alkaline proteases) in the anterior (AI) and posterior (PI) intestine and tissue morphology (pyloric caeca-PC, AI, PI, distal intestine-DI and liver). For that purpose, fish were fed the experimental diets for 36 days and then liver and intestine were sampled at 2, 6 and 24 h after the last meal. Alkaline protease characterization was also done in AI and PI at 6 h post-feeding. Dietary VO promoted higher alkaline phosphatase activity at 2 h post-feeding in the AI and at all sampling points in the PI. Total alkaline protease activity was higher at 6 h post-feeding in the PI of fish fed the FO diet. Identical number of bands was observed in zymograms of alkaline proteases of fish fed both diets. No alterations in the histomorphology of PC, AI, PI or DI were noticed in fish fed the VO diets, while in the liver a tendency towards increased hepatocyte vacuolization due to lipid accumulation was observed. Overall, and with the exception of a higher intestine alkaline phosphatase activity, 70% FO replacement by a VO blend in diets for European sea bass resulted in no distinctive alterations on the postprandial pattern of digestive enzyme activities and intestine histomorphology. PMID- 26364217 TI - Carbon nanoparticle induced cytotoxicity in human mesenchymal stem cells through upregulation of TNF3, NFKBIA and BCL2L1 genes. AB - Carbon based nanomaterials, including carbon nanotubes, graphene, nanodiamond and carbon nanoparticles, have emerged as potential candidates for a wide variety of applications because of their unusual electrical, mechanical, thermal and optical properties. However, our understanding of how increased usage of carbon based nanomaterials could lead to harmful effects in humans and other biological systems is inadequate. Our present investigation is focused on the cellular toxicity of carbon nanoparticles (CNPs) on human mesenchymal stem cells (hMSCs). Following exposure to CNPs, cell viability, nuclear morphological changes, apoptosis and cell cycle progression were monitored. Furthermore, the expression of genes involved in both cell death (e.g., P53, TNF3, CDKN1A, TNFRSF1A, TNFSF10, NFKBIA, BCL2L1) and cell cycle regulation (e.g., PCNA, EGR1, E2F1, CCNG1, CCND1, CCNC, CYCD3) were assessed using qPCR. Our results indicated that CNPs reduce cell viability and cause chromatin condensation and DNA fragmentation. Cell cycle analysis indicated that CNPs affect the cell cycle progression. However, the gene expression measurements confirmed that CNPs significantly upregulated the P53, TNF3, CDKNIA, and NFKBIA genes and downregulated the EGR1 gene in hMSCs. Our findings suggest that CNPs reduce cell viability by disrupting the expression of cell death genes in human mesenchymal stem cell (hMSC). The results of this investigation revealed that CNPs exhibited moderate toxicity on hMSCs. PMID- 26364218 TI - Sorption of four hydrophobic organic contaminants by biochars derived from maize straw, wood dust and swine manure at different pyrolytic temperatures. AB - Sorption behavior of acetochlor (ACE), dibutyl phthalate (DBP), 17alpha-Ethynyl estradiol (EE2) and phenanthrene (PHE) with biochars produced from three feedstocks (maize straw (MABs), pine wood dust (WDBs) and swine manure (SWBs)) at seven heat treatment temperatures (HTTs) was evaluated. The bulk polarity of these biochars declined with increasing HTT while the aromaticity and CO2-surface area (CO2-SA) rose. The surface OC contents of biochars were generally higher than bulk OC contents. The organic carbon (OC)-normalized CO2-SA (CO2-SA/OC) of biochars significantly correlated with the sorption coefficients (n and logK(oc)), suggesting that pore filling could dominate the sorption of tested sorbates. SWBs had higher logK(oc) values compared to MABs and WDBs, due to their higher ash contents. Additionally, the logK(oc) values for MABs was relatively greater than that for WDBs at low HTTs (<=400 degrees C), probably resulting from the higher CO2-SA/OC, ash contents and aromaticity of MABs. Surface polarity and the aliphatic C may dominate the sorption of WDBs obtained at relatively low HTTs (<=400 degrees C), while aromatic C affects the sorption of biochars at high HTTs. Results of this work aid to deepen our understanding of the sorption mechanisms, which is pivotal to wise utilization of biochars as sorbents for hazardous organic compounds. PMID- 26364219 TI - Degradation of triclocarban by a triclosan-degrading Sphingomonas sp. strain YL JM2C. AB - Bacterial degradation plays a vital role in determining the environmental fate of micropollutants like triclocarban. The mechanism of triclocarban degradation by pure bacterium is not yet explored. The purpose of this study was to identify metabolic pathway that might be involved in bacterial degradation of triclocarban. Triclosan-degrading Sphingomonas sp. strain YL-JM2C was first found to degrade up to 35% of triclocarban (4 mg L(-1)) within 5 d. Gas chromatography mass spectrometry detected 3,4-dichloroaniline, 4-chloroaniline and 4 chlorocatechol as the major metabolites of the triclocarban degradation. Furthermore, total organic carbon results confirmed that the intermediates, 3,4 dichloroaniline (4 mg L(-1)) and 4-chloroaniline (4 mg L(-1)) could be degraded up to 77% and 80% by strain YL-JM2C within 5 d. PMID- 26364220 TI - Formation of haloacetonitriles and haloacetamides and their precursors during chlorination of secondary effluents. AB - The formation of dichloroacetonitrile (DCAN), dichloroacetamide (DCAcAm) and trichloroacetamide (TCAcAm) during chlorination of secondary effluents was evaluated under different conditions. The formation of DCAN and DCAcAm increased, then decreased with increasing contact time and chlorine dose, while TCAcAm formation increased continually, exceeding DCAcAm formation after a relatively long contact time or in response to a relatively high chlorine dose (20-80 mg L( 1)). Increasing the sample pH from 6 to 9 reduced the formation of DCAN and TCAcAm, while DCAcAm formation was highest at pH 8. Precursors in the secondary effluent were characterized by separating the organic matter into several fractions using membrane filtration and XAD resins and then measuring the formation of DCAN, DCAcAm and TCAcAm from each fraction during chlorination. Dissolved organic matter (DOM) with a molecular weight less than 1 kDa dominated the formation of DCAcAm and TCAcAm. However, particle-associated DCAN precursors were detected in addition to potent DCAN precursors in the DOM fractions. Among the XAD fractions of DOM, the hydrophilic neutral fraction prevailed in the secondary effluent and produced the most DCAN, DCAcAm and TCAcAm per volume, and the hydrophilic basic fraction with a low organic content had the highest yields of DCAN, DCAcAm and TCAcAm on a DOC basis, so their dominant precursors were associated with hydrophilic matter. PMID- 26364221 TI - Non-monotonic dose-response effect of bisphenol A on rare minnow Gobiocypris rarus ovarian development. AB - Bisphenol A (BPA) is widely spread in the environment, and can cause various reproductive disrupting effects on different organisms, including fish. Our previous published study showed that BPA has non-monotonic (inverted U-shaped) dose-response effect on rare minnow Gobiocypris rarus ovarian weight at different concentrations. To investigate the potential mechanism, we exposed female rare minnow to 1, 15 and 225 ug L(-1) BPA for 7 days in the present study. The levels of vitellogenin (Vtg), sex hormones, hydrogen peroxide (H2O2), glutathione (GSH) and triglyceride (TG) were measured. RNA-seq of ovary tissues was also performed. Result showed that Vtg, sex hormone and TG levels showed an inverted U-shaped increased response, while H2O2 and GSH levels showed a U-shaped inhibited response. RNA-seq data showed that many genes involved in lipid metabolism, oxidative stress, and proteolysis processes were altered. The change of Vtg, H2O2, GSH and TG levels was possibly related to the altered sex hormone levels. Sex hormone's direct effect, Vtg accumulation, TG accumulation and oxidative stress induced proteolysis may contribute to the change of ovary weight. PMID- 26364222 TI - Fate of pharmaceuticals in full-scale source separated sanitation system. AB - Removal of 14 pharmaceuticals and 3 of their transformation products was studied in a full-scale source separated sanitation system with separate collection and treatment of black water and grey water. Black water is treated in an up-flow anaerobic sludge blanket (UASB) reactor followed by oxygen-limited autotrophic nitrification-denitrification in a rotating biological contactor and struvite precipitation. Grey water is treated in an aerobic activated sludge process. Concentration of 10 pharmaceuticals and 2 transformation products in black water ranged between low MUg/l to low mg/l. Additionally, 5 pharmaceuticals were also present in grey water in low MUg/l range. Pharmaceutical influent loads were distributed over two streams, i.e. diclofenac was present for 70% in grey water, while the other compounds were predominantly associated to black water. Removal in the UASB reactor fed with black water exceeded 70% for 9 pharmaceuticals out of the 12 detected, with only two pharmaceuticals removed by sorption to sludge. Ibuprofen and the transformation product of naproxen, desmethylnaproxen, were removed in the rotating biological contactor. In contrast, only paracetamol removal exceeded 90% in the grey water treatment system while removal of other 7 pharmaceuticals was below 40% or even negative. The efficiency of pharmaceutical removal in the source separated sanitation system was compared with removal in the conventional sewage treatment plants. Furthermore, effluent concentrations of black water and grey water treatment systems were compared with predicted no effect concentrations to assess toxicity of the effluent. Concentrations of diclofenac, ibuprofen and oxazepam in both effluents were higher than predicted no-effect concentrations, indicating the necessity of post-treatment. Ciprofloxacin, metoprolol and propranolol were found in UASB sludge in MUg/g range, while pharmaceutical concentrations in struvite did not exceed the detection limits. PMID- 26364223 TI - Mathematical model for interactions and transport of phosphorus and sediment in the Three Gorges Reservoir. AB - Phosphorus fate and transport in natural waters plays a crucial role in the ecology of rivers and reservoirs. In this paper, a coupled model of hydrodynamics, sediment transport, and phosphorus transport is established, in which the effects of sediment on phosphorus transport are considered in detail. Phosphorus adsorption is estimated using a mechanistic surface complexation model which is capable of simulating the adsorption characteristics under various aquatic chemistry conditions. The sediment dynamics are analyzed to evaluate the deposition and release of phosphorus at the bed surface. In addition, the aerobic layer and anaerobic layer of the sediments are distinguished to study the distribution of phosphorus between dissolved and particulate phases in the active sediment layer. The proposed model is applied to evaluate the effects of various operating rules on sediment and phosphorus retention in the Three Gorges Reservoir (TGR). Results show that the proposed model can reasonably reflect the phosphorus transport with sediment, and management scenarios that influence sediment retention will also influence the phosphorus balance in the TGR. However, modest operational changes which have only minor effects on sediment retention also have limited influence on the phosphorous balance. PMID- 26364224 TI - Hydrogen and lipid production from starch wastewater by co-culture of anaerobic sludge and oleaginous microalgae with simultaneous COD, nitrogen and phosphorus removal. AB - Anaerobic sludge (AS) and microalgae were co-cultured to enhance the energy conversion and nutrients removal from starch wastewater. Mixed ratio, starch concentration and initial pH played critical roles on the hydrogen and lipid production of the co-culture system. The maximum hydrogen production of 1508.3 mL L(-1) and total lipid concentration of 0.36 g L(-1) were obtained under the optimized mixed ratio (algae:AS) of 30:1, starch concentration of 6 g L(-1) and initial pH of 8. The main soluble metabolites in dark fermentation were acetate and butyrate, most of which can be consumed in co-cultivation. When sweet potato starch wastewater was used as the substrate, the highest COD, TN and TP removal and energy conversion efficiencies reached 80.5%, 88.7%, 80.1% and 34.2%, which were 176%, 178%, 200% and 119% higher than that of the control group (dark fermentation), respectively. This research provided a novel approach and achieved efficient simultaneous energy recovery and nutrients removal from starch wastewater by the co-culture system. PMID- 26364225 TI - Effects of activated carbon ageing in three PCB contaminated sediments: Sorption efficiency and secondary effects on Lumbriculus variegatus. AB - The sorption efficiency and possible secondary effects of activated carbon (AC) (o 63-200 MUm) was studied with Lumbriculus variegatus in three PCB contaminated sediments applying long AC-sediment contact time (3 years). AC amendment efficiently reduced PCB bioavailability as determined with both, L. variegatus bioaccumulation test and passive samplers. However, dose related secondary effects of AC on egestion rate and biomass were observed (applied doses 0.25% and 2.5% sediment dry weight). The sorption capacity and secondary effects remained similar when the experiments were repeated after three years of AC-sediment contact time. Further, transmission electron microscopy (TEM) samples revealed morphological changes in the L. variegatus gut wall microvilli layer. Sediment properties affected both sorption efficiency and secondary effects, but 2.5% AC addition had significant effects regardless of the sediment. In, conclusion, AC is an efficient and stable sorbent to decrease the bioavailability of PCBs. However, sediment dwelling organisms, such as Oligochaete worms in this study, may be sensitive to the carbon amendments. The secondary effects and possible morphological changes in benthic organisms should not be overlooked as in many cases they form the basis of the aquatic food webs. PMID- 26364226 TI - Sulfur-based mixotrophic denitrification corresponding to different electron donors and microbial profiling in anoxic fluidized-bed membrane bioreactors. AB - Sulfur-based mixotrophic denitrifying anoxic fluidized bed membrane bioreactors (AnFB-MBR) were developed for the treatment of nitrate-contaminated groundwater with minimized sulfate production. The nitrate removal rates obtained in the methanol- and ethanol-fed mixotrophic denitrifying AnFB-MBRs reached 1.44-3.84 g NO3 -N/L reactor d at a hydraulic retention time of 0.5 h, which were significantly superior to those reported in packed bed reactors. Compared to methanol, ethanol was found to be a more effective external carbon source for sulfur-based mixotrophic denitrification due to lower sulfate and total organic carbon concentrations in the effluent. Using pyrosequencing, the phylotypes of primary microbial groups in the reactor, including sulfur-oxidizing autotrophic denitrifiers, methanol- or ethanol-supported heterotrophic denitrifiers, were investigated in response to changes in electron donors. Principal component and heatmap analyses indicated that selection of electron donating substrates largely determined the microbial community structure. The abundance of Thiobacillus decreased from 45.1% in the sulfur-oxidizing autotrophic denitrifying reactor to 12.0% and 14.2% in sulfur-based methanol- and ethanol-fed mixotrophic denitrifying bioreactors, respectively. Heterotrophic Methyloversatilis and Thauera bacteria became more dominant in the mixotrophic denitrifying bioreactors, which were possibly responsible for the observed methanol- and ethanol-associated denitrification. PMID- 26364227 TI - Surprisingly low infertility rate in married type 2 diabetic women: A rather curious paradox to the current opinion of insulin resistance as the joint pathogenesis of poly cystic ovary syndrome and type 2 diabetes mellitus. AB - BACK GROUND: Sharing the same pathophysiologic principle which is insulin resistance, type 2 diabetes mellitus (T2DM) and poly cystic ovary syndrome (PCOS) are usually considered closely related and easily interchangeable medical entities. Numerous attempts have been made to document this illusory perspective. OBJECTIVE: Based on a delicate pathophysiologic notion, we believe that fully developed T2DM is infrequently observed with fully featured PCOS. MATERIALS AND METHODS: In an observational descriptive study 257 married T2DM women were consecutively included and meticulously investigated for fertility history and, albeit, clinical and biochemical features of PCOS. RESULTS: Of 257 married diabetic women only six (2.3%) had no children. In one case a male problem (azoospermia) and in the second case, late marriage (aged 45 at wedding ceremony) was the cause of infertility. Thus, only four (1.6%) might have been labeled as true female factor infertility. Astounding to report was the average pregnancies for each participant which was 5.1+/-2.5, ranging from zero to fifteen. CONCLUSION: we would suggest that, despite the well-established fact of insulin resistance as the common pathophysiologic process for T2DM and PCOS, they are definitely separate medical entities. As a matter of fact T2DM and PCOS are the two opposite aspect of the insulin resistance coin. PMID- 26364228 TI - Characterization of biochars derived from agriculture wastes and their adsorptive removal of atrazine from aqueous solution: A comparative study. AB - The physicochemical properties of biochars produced from soybeans (SBB), corn stalks (CSB), rice stalks (RSB), poultry manure (PMB), cattle manure (CMB), and pig manure (PgMB) and their adsorption characteristics of atrazine were investigated. The adsorption capacity increased with the increase of temperature and initial atrazine concentration. More atrazine was removed from basic solutions than acidic solutions, due to the effects of adsorption and hydrolysis. The Freundlich isotherm adsorption parameters indicated that the adsorption capacity decreased in the order SBB>RSB>CMB>CSB>PMB>PgMB, which is associated to the pore volume of biochars. The total pore volume and biochar pH were concluded to play important roles in determining the adsorption capacity, and they may have contributed to physical adsorption mechanisms dominating the overall adsorption process (the low activation energy for all of the biochars). Modified Freundlich and intraparticle diffusion models were used to describe the kinetics of the adsorption process. PMID- 26364229 TI - Enhanced production of recombinant Escherichia coli glutamate decarboxylase through optimization of induction strategy and addition of pyridoxine. AB - This report describes the optimization of recombinant Escherichia coli glutamate decarboxylase (GAD) production from engineered E. coli BL21(DE3) in a 3-L fermentor. Investigation of different induction strategies revealed that induction was optimal when the temperature was maintained at 30 degrees C, the inducer (lactose) was fed at a rate of 0.2 g L(-1)h(-1), and protein expression was induced when the cell density (OD600) reached 50. Under these conditions, the GAD activity of 1273.8 U mL(-1) was achieved. Because GAD is a pyridoxal 5' phosphate (PLP)-dependent enzyme, the effect of supplementing the medium with pyridoxine hydrochloride (PN), a cheap and stable PLP precursor, on GAD production was also investigated. When the culture medium was supplemented with PN to a concentration of 2mM at the initiation of protein expression, and then again 10h later, the GAD activity reached 3193.4 U mL(-1), which represented the highest GAD production ever reported. PMID- 26364230 TI - Stoichiometry and kinetics of the anaerobic ammonium oxidation (Anammox) with trace hydrazine addition. AB - Purpose of this study is to investigate the stoichiometry and kinetics of anaerobic ammonium oxidation (Anammox) with trace hydrazine addition. The stoichiometry was established based on the electron balance of Anammox process with trace N2H4 addition. The stoichiometric coefficients were determined by the proton consumption and the changes in substrates and products. It was found that trace N2H4 addition can increase the yield of Anammox bacteria (AnAOB) and reduce NO3(-) yield, which enhances the Anammox. Subsequently, kinetic model of Anammox with trace N2H4 addition was developed, and the parameters of the anaerobic degradation model of N2H4 were obtained for the first time. The maximum specific substrate utilization rate, half-saturation constant and inhibition constant of N2H4 were 25.09mgN/g VSS/d, 10.42mgN/L and 1393.88mgN/L, respectively. These kinetic parameters might provide important information for the engineering applications of Anammox with trace N2H4 addition. PMID- 26364231 TI - Combination of RNA sequencing and metabolite data to elucidate improved toxic compound tolerance and butanol fermentation of Clostridium acetobutylicum from wheat straw hydrolysate by supplying sodium sulfide. AB - Sodium sulfide (SS) was added to the non-detoxified wheat straw hydrolysate for ABE fermentation by Clostridium acetobutylicum CICC8012. Biochemical measurements demonstrated that supplementation with SS promoted earlier and enhanced conversion of acid to ABE and led to a 27.48% improvement in sugar consumption, a 20.48% improvement in the sugar-based ABE yield, a 47.63% improvement in the butanol titer, and a 53.50% improvement in the ABE concentration. The response of C. acetobutylicum CICC8012 at the mRNA level was examined by a transcriptional analysis performed with RNA sequencing. The expression of genes involved in the membrane transport of carbohydrates, glycolysis, and ABE formation increased following SS-supplemented fermentation, whereas the expression of genes encoding enzymes involved in acid formation decreased, which indicates that supplemental SS affected the central fermentative pathway, down-regulated the metabolic flux toward the acid formation branches, and up-regulated the metabolic flux toward the ABE formation branches. PMID- 26364233 TI - Metabolomics of Disease Resistance in Crops. AB - Plants are continuously exposed to the attack of invasive microorganisms, such as fungi or bacteria, and also viruses. To fight these attackers, plants develop different metabolic and genetic responses whose final outcome is the production of either toxic compounds that kill the pathogen or deter its growth, and/or semiotic molecules that alert other individuals from the same plant species. These molecules are derived from the secondary metabolism and their production is induced upon detection of a pathogen-associated molecular pattern (PAMP). These PAMPs are different molecules that are perceived by the host cell triggering defense responses. PAMP-elicited compounds are highly diverse and specific of every plant species and can be divided into preformed metabolites or phytoanticipins that are converted into toxic molecules upon pathogen perception, and toxic metabolites or phytoalexins that are produced only upon pathogen attack. Moreover, plant volatile emissions are also modified in response to pathogen attack to alert neighboring individuals or to make plants less attractive to pathogen vector arthropods. Plant metabolite profiling techniques have allowed the identification of novel antimicrobial molecules that are induced upon elicitation. However, more studies are required to assess the specific function of metabolites or metabolite blends on plant-microbe interactions. PMID- 26364232 TI - Frequency content and characteristics of ventricular conduction. AB - The spectrum of frequencies producing the QRS complex has not been fully explored. In this manuscript we review previous studies of QRS frequency content, and discuss our novel method of the conjoint analysis of the ECG signal in six dimensions: in the domain of three space dimensions, in time domain, and in frequency domain. Orbital frequency of QRS loop is introduced as a six dimensional characteristic of ventricular conduction, which helped to reveal inapparent ventricular conduction, and to characterize electrophysiological substrate. In this paper, we review our novel method in the historical context. PMID- 26364234 TI - A New Technique to Increase Reliability in Measuring the Axis of Bone. AB - Measuring bone angles is an important method for diagnosing disease and predicting the prognosis in orthopedics. Traditionally, the angle is measured using lines drawn manually and adjusted by the naked eye. The purpose of the present study was to propose new methods to measure the bone angles formed by the axes of the calcaneus with good reliability and low operational error. The 2 new methods used linear regression analysis of the points inside and on the "envelope" line. The traditional method used the vector of the lines drawn for calculation. Digital radiographs of the lateral view of the feet from 51 patients were collected, and the angles were measured using these 3 methods. Next, we analyzed the reliability, differences, and correlations of these 3 methods. The intra- and interobserver comparisons revealed significant differences between the results of the 2 new methods and those of the traditional method. In addition, the new methods had greater reliability and better intra- and interobserver correlations than did the traditional method. We suggest that these 2 new methods to measure bone axis should be added to the Picture Archiving and Communication System to obtain more reliable and standardized data in clinical practice and for future research purposes. PMID- 26364235 TI - Arthroscopic Resection of a Bilateral Calcaneonavicular Coalition in a Child. AB - Calcaneonavicular coalition is a congenital anomaly characterized by a connection between the calcaneus and the navicular. It can manifest as lateral foot pain, peroneal spastic flatfoot, and repeated ankle sprains. Surgery is required in the case of chronic pain and after failure of conservative treatment. The aim of surgical intervention is pain relief and preventing recurrence. Arthroscopic resection is a minimally invasive alternative that has the advantages of quicker recovery and better aesthetic results. This technique has shown significant symptomatic improvement and no recurrence at early follow-up points in a small number of reported cases. The present report presents the case of a child with bilateral calcaneonavicular coalition. This is the first report to our knowledge that describes the outcome of simultaneous bilateral arthroscopic resection of calcaneonavicular coalition in a child with a 2-year follow-up period. PMID- 26364236 TI - Pedobarography in the Assessment of Postoperative Calcaneal Fracture Pressure With Gait. AB - The purpose of the present study was to evaluate the benefits and importance of pedobarography in the diagnosis and treatment of plantar pressure changes in the postoperative follow-up of calcaneus fractures treated with open reduction and internal fixation. The 28 patients included 23 males (82%) and 5 females (18%). The clinical evaluation was performed using the American Orthopaedic Foot and Ankle Society hindfoot scoring system. The Bohler and Gissane angles were measured on the preoperative and postoperative radiographs. In the postoperative follow-up period (mean +/- standard deviation 22.25 +/- 10.8 months), all the patients underwent analysis with a dynamic pedobarogram. Because the arch index of the operated feet was 29.73% and that of the nonoperated feet was 28.94%, a similar slightly low arch was seen in both feet (p = .078). When the plantar surface maximum pressures were evaluated, a significant reduction was seen in the operated feet in the second, third, fourth, and fifth metatarsals and the medial hindfoot (p < .05). Displaced intra-articular calcaneus fractures resulted in a significant reduction in maximum pressure of the second, third, fourth, and fifth metatarsals and the medial hindfoot. Also, the hindfoot pressure was lateralized. Pedobarography is a simple and useful method for the diagnosis of plantar pressure changes occurring postoperatively. PMID- 26364238 TI - RNAseq and Proteomics for Analysing Complex Oomycete Plant Interactions. AB - The oomycetes include some of the most devastating plant pathogens. In this review we discuss the latest results from oomycete and plant studies with emphasis on interaction studies. We focus on the outcomes of RNAseq and proteomics studies and some pitfalls of these approaches. Both pathogenic interactions and biological control are discussed. We underline the usefulness of studies at several levels of complexity from studies of one organism, up to two or more and within agricultural fields (managed settings) up to wild ecosystems. Finally we identify areas of future interest such as detailed interactome studies, dual RNAseq studies, peptide modification studies and population/meta omics with or without biological control agents. PMID- 26364239 TI - A liquid chromatography-tandem mass spectrometry-based investigation of the lamellar interstitial metabolome in healthy horses and during experimental laminitis induction. AB - Lamellar bioenergetic failure is thought to contribute to laminitis pathogenesis but current knowledge of lamellar bioenergetic physiology is limited. Metabolomic analysis (MA) can systematically profile multiple metabolites. Applied to lamellar microdialysis samples (dialysate), lamellar bioenergetic changes during laminitis (the laminitis metabolome) can be characterised. The objectives of this study were to develop a technique for targeted MA of lamellar and skin dialysates in normal horses, and to compare the lamellar and plasma metabolomic profiles of normal horses with those from horses developing experimentally induced laminitis. Archived lamellar and skin dialysates (n = 7) and tissues (n = 6) from normal horses, and lamellar dialysate and plasma from horses given either 10 g/kg oligofructose (treatment group, OFT; n = 4) or sham (control group, CON; n = 4) were analysed. The concentrations of 44 intermediates of central carbon metabolism (CCM) were determined using liquid chromatography-tandem mass spectrometry. Data were analysed using multivariate (MVA) and univariate (UVA) analysis methods. The plasma metabolome appeared to be more variable than the lamellar metabolome by MVA, driven by malate, pyruvate, aconitate and glycolate. In lamellar dialysate, these metabolites decreased in OFT horses at the later time points. Plasma malate was markedly increased after 6 h in OFT horses. Plasma malate concentrations between OFT and CON at this time point were significantly different by UVA. MA of lamellar CCM was capable of differentiating horses developing experimental laminitis from controls. Lamellar malate, pyruvate, aconitate and glycolate, and plasma malate alone were identified as the source of differentiation between OFT and CON groups. These results highlighted clear discriminators between OFT and CON horses, suggesting that changes in energy metabolism occur locally in the lamellar tissue during laminitis development. The biological significance of these alterations requires further investigation. PMID- 26364240 TI - Significance of caveolin-1 and matrix metalloproteinase 14 gene expression in canine mammary tumours. AB - Canine mammary tumours (CMTs) are the most common neoplasms affecting female dogs. There is an urgent need for molecular biomarkers that can detect early stages of the disease in order to improve accuracy of CMT diagnosis. The aim of this study was to examine whether caveolin-1 (Cav-1) and matrix metalloproteinase 14 (MMP14) are associated with CMT histological malignancy and invasion. Sixty five benign and malignant CMT samples and six normal canine mammary glands were analysed using quantitative reverse transcription-polymerase chain reaction. Cav 1 and MMP14 genes were highly expressed in CMT tissues compared to normal tissues. Cav-1 especially was overexpressed in malignant and invasive CMT tissues. When a CMT cell line was cultured on fluorescent gelatin-coated coverslips, localisation of Cav-1 was observed at invadopodia-mediated degradation sites of the gelatin matrix. These findings suggest that Cav-1 may be involved in CMT invasion and that the markers may be useful for estimating CMT malignancy. PMID- 26364241 TI - NED (No Evidence of Disease). PMID- 26364237 TI - European surveillance for enterovirus D68 during the emerging North-American outbreak in 2014. AB - BACKGROUND: In August and September 2014, unexpected clusters of enterovirus-D68 (EV-D68) infections associated with severe respiratory disease emerged from North America. In September, the European Centre for Disease Prevention and Control (ECDC) asked European countries to strengthen respiratory sample screening for enterovirus detection and typing in cases with severe respiratory presentations. OBJECTIVES: To provide a detailed picture of EV-D68 epidemiology in Europe by conducting a retrospective and prospective laboratory analysis of clinical specimens. STUDY DESIGN: An initiative supported by the European Society for Clinical Virology (ESCV) and ECDC was launched to screen for EV-D68 in respiratory specimens between July 1st and December 1st 2014 in Europe and to sequence the VP1 region of detected viruses for phylogenetic analytic purposes. RESULTS: Forty-two institutes, representing 51 laboratories from 17 European countries, analyzed 17,248 specimens yielding 389 EV-D68 positive samples (2.26%) in 14 countries. The proportion of positive samples ranged between 0 and 25% per country. These infections resulted primarily in mild respiratory disease, mainly detected in young children presenting with wheezing and in immuno-compromised adults. The viruses detected in Europe are genetically very similar to those of the North-American epidemic and the majority (83%) could be assigned to clade B. Except for 3 acute flaccid paralysis (AFP) cases, one death and limited ICU admissions, no severe cases were reported. CONCLUSIONS: The European study showed that EV-D68 circulated in Europe during summer and fall of 2014 with a moderate disease burden and different pathogenic profile compared to the North-American epidemic. PMID- 26364242 TI - Revision of margins under frozen section in oral cancer: a retrospective study of involved margins in pT1 and pT2 oral cancers. AB - Operative assessment of the resection margins by frozen section is routine in many hospitals, but the usefulness of the technique relies on its sensitivity, specificity, sampling errors, and errors associated with relocation of involved margins. Its usefulness is indicated by assessment of overall survival and locoregional recurrence in patients whose margins were initially involved but were successfully revised after frozen section compared with those of the patients whose initially-involved margins were not revised. Patients with consecutive primary pT1, pT2 oral squamous cell carcinoma in whom initial resection resulted in involved margins were selected from the patients treated during the period January 2010 to December 2011 at a tertiary cancer hospital in India. The outcome of patients whose revision of margins after frozen section was successful was compared with that of patients who had "false negative" results after frozen section. Sixty-eight patients had involved margins after initial resection, of whom 42 (62%) had successful revision after frozen section (clear margins group). The remaining 26 patients (38%) had "false negative" results on frozen section, and had no further revision (invaded margins group). Local recurrence was more common in the invaded margins group, although not significantly so in this short retrospective series (p=0.08). The risk of death was greater in patients with local recurrence, hazard ratio (HR) 4.74 (95% CI 1.79 to 12.61, p=0.002). However, overall survival (p=0.73), incidence of locoregional recurrence (p=0.59) and neck recurrence (p=1.0), did not differ significantly between the groups. PMID- 26364243 TI - Frontal plane kinematics of the hip during running: Are they related to hip anatomy and strength? AB - Excessive hip adduction has been associated with a number of lower extremity overuse running injuries. The excessive motion has been suggested to be the result of reduced strength of the hip abductor musculature. Hip anatomical alignment has been postulated to influence hip abduction (HABD) strength and thus may impact hip adduction during running. The purpose of this study was to investigate the relationship between hip anatomy, HABD strength, and frontal plane kinematics during running. Peak isometric HABD strength, 3D lower extremity kinematics during running, femoral neck-shaft angle (NSA), and pelvis width-femur length (PW-FL) ratio were recorded for 25 female subjects. Pearson correlations (p<0.05) were performed between variables. A fair relationship was observed between femoral NSA and HABD strength (r=-0.47, p=0.02) where an increased NSA was associated with reduced HABD strength. No relationship was observed between HABD strength and hip adduction during running. None of the anatomical measurements, NSA or PW-FL, were associated with hip adduction during running. Deviations in the femoral NSA have a limited ability to influence peak isometric hip abduction strength or frontal plane hip kinematics during running. Hip abduction strength does also not appear to be linked with changes in hip kinematics. These findings in healthy individuals question whether excessive hip adduction typically seen in female runners with overuse injuries is caused by deviations in hip abduction strength or anatomical structure. PMID- 26364244 TI - National dental waitlists: what would it take to reset to zero? AB - Objective Over the years, long public dental waitlists across Australia have received much attention from the media. The issue for eligible patients, namely a further deterioration of dental health because of not being able to address dental concerns relatively quickly, has been the subject of several state and Federal initiatives. The present study provides a cost model for eliminating public dental waitlists across Australia and compares these results with the cost of contracting out public dental care to private clinics. Methods Waitlist data from across Australia were collected from publicly available sources and confirmed through direct communication with each individual State or Territory Dental Health body. Average costs associated with employing key dental personnel and performance figures were used from previously published data to estimate the potential financial commitment and probable public benefits. Results The cost model suggests that, on average, it would be more than twice as expensive to contract the work out to private dental clinics as to treat eligible patients within public dental clinics. It is estimated that the cost of eliminating the legacy dental waiting lists (over 12 months) would be between A$50 and A$100million depending on the method adopted. The effort would require some 360 dental teams. Conclusion The design of the Australian public dental care system that is targeted at meeting the needs of eligible patients into the future, in addition to being effective and sustainable, must also offer a level of protection to the taxpayer. The ability to address waitlist backlog identified in the present study clearly would require a mix of service models depending on service availability at different locations. Further research is needed to optimise the mix of service providers to address community needs. What is known about the topic? Long public dental waitlists across Australia have received much attention from the media. The topic has been the subject of debate at the government level and, over the years, has seen an increase in allocation of public funds in an effort to address the policy needs. What does this paper add? This study calculates the actual number of people on the public dental waitlist, provides a detailed analysis of the distribution of the demand for the services and offers a cost model for resetting public dental waitlists across Australia. What are the implications for practitioners? This study carries no implications for individual practitioners at the clinical level. However, at the state and national levels, this model offers direction to a more cost-effective allocation of public funds and human resources. PMID- 26364245 TI - Listing on MEDLINE: A new milestone for the Australian Journal of Physiotherapy. AB - The Editorial Board is pleased to announce that, commencing with the first issue of Volume 47, the Australian Journal of Physiotherapy will now be listed in the prestigious MEDLINE database. It has long been a goal of past and current Editorial Boards to achieve listing with MEDLINE because of the international exposure that such listing brings. Of the estimated 13,000 to 14,000 biomedical titles currently published throughout the world, about 4,500 titles are indexed and included in the MEDLINE database. MEDLINE is the principal online bibliographic citation database of MEDLARS system of the National Library of Medicine (USA) and includes all the citations published in Index Medicus as well as the citations published in two other indices, the Index to Dental Literature (IDL) and the International Nursing Index (INI). PMID- 26364246 TI - AJP Forum: Pre-Manipulative Testing of the Cervical Spine. AB - This issue of the Journal includes a new feature: the 'AJP Forum'. The Editorial Board envisages that this feature will be used from time to time to provide a venue for expert comment on issues of importance for physiotherapy practice. The first Forum examines issues related to premanipulative testing of the cervical spine. It follows the Australian Physiotherapy Association's recent release of Clinical Guidelines for Pre-Manipulative Procedures for the Cervical Spine (Magarey et al 2000). The 2000 guidelines replace the protocol published in 1988. PMID- 26364247 TI - The Musculoskeletal Physiotherapy of Australia position on pre-manipulative testing for the cervical spine. AB - The MPA undertook a survey of its members in 1997 to determine their compliance with and opinion of the APA Protocol for Pre-Manipulative Testing of the Cervical Spine (Magarey et al 2000a, Magarey et al submitted-a). As a result of that survey and a comprehensive literature review, the MPA developed a new set of guidelines for premanipulative procedures for the cervical spine (Magarey et al 2000b, Magarey et al submitted-b). PMID- 26364248 TI - Are we on the right track? AB - We applaud Musculoskeletal Physiotherapy Australia for the formulation of the new Pre-Manipulative guidelines. The new guidelines are a step forward from the previous protocol because they allow individual practitioners choice when making clinical decisions. The previous protocol proved to be legally challenging and further increased practitioners' fear of manipulating. PMID- 26364249 TI - Pre-manipulative testing: predicting risk or pretending to? AB - Clinical practice guidelines should be evidence-based and useful. Unfortunately, the APA guidelines largely are not. Their recommendations include. PMID- 26364250 TI - Do the guidelines do what they are supposed to? AB - The unwritten purpose of the guidelines appears to be to reduce risk to patients of cervical manipulation and to provide legal indemnity to physiotherapists. Do the guidelines achieve this purpose? PMID- 26364251 TI - Guidelines for pre-manipulative testing of the cervical spine - an appraisal. AB - Are the guidelines valid? It is not clear if recommendations were derived from evidence of high quality or from evidence that is much more liable to error. The majority of evidence is based on low level evidence; that is, physiology, bench research, or "first principles" (Sackett et al 2000). Studies of moderate level evidence, where inappropriate sampling and a narrow spectrum of study individuals was used, revealed vertebrobasilar insufficiency tests to be invalid. Information on the validity of the diagnostic studies, their accuracy, and detailed instruction for applying that evidence to our patients (Sackett et al 2000) was not reported in the guidelines. PMID- 26364252 TI - A valid pre-manipulative screening tool is needed. AB - The Australian Physiotherapy Association's Clinical Guidelines for Pre Manipulative Procedures for the Cervical Spine represent a positive step towards the goal of reducing the incidence of vertebrobasilar strokes following neck manipulation. Nevertheless, the predictive value of the guidelines is largely contingent upon the validity of the physical screening tests, particularly sustained end-range cervical rotation. The primary issue is the sensitivity of the tests for detecting patients with vertebral artery occlusion and vertebrobasilar insufficiency, and who are at high risk of experiencing significant forces during manipulation which could result in intimal dissection. PMID- 26364253 TI - Influence of vertebral artery blood flow research outcomes on clinical judgment. AB - There has been substantial additional research into the effects of cervical movements on vertebral artery blood flow since 1988, when the APA first formalised a Protocol for Pre-Manipulative Testing of the Cervical Spine and recommended its use in patients with upper quarter dysfunction. The development of duplex Doppler ultrasound equipment with colour enhancement, which allows measurements of velocity and flow rate of vertebral artery blood flow, has resulted in a burgeoning of in-vivo blood flow studies. PMID- 26364254 TI - Recovery study of cholinesterases and neurotoxic signs in the non-target freshwater invertebrate Chilina gibbosa after an acute exposure to an environmental concentration of azinphos-methyl. AB - Azinphos-methyl belongs to the class of organophosphate insecticides which are recognized for their anticholinesterase action. It is one of the most frequently used insecticides in the Upper Valley of Rio Negro and Rio Neuquen in Argentina, where agriculture represents the second most important economic activity. It has been detected in water from this North Patagonian region throughout the year and the maximum concentration found was 22.48 MUg L(-1) during the application period. Chilina gibbosa is a freshwater gastropod widely distributed in South America, particularly in Patagonia, Argentina and in Southern Chile. Toxicological studies performed with C. gibbosa in our laboratory have reported neurotoxicity signs and cholinesterase inhibition after exposure to azinphos methyl for 48 h. Recovery studies together with characterization of the enzyme and sensitivity of the enzyme to pesticides can improve the toxicological evaluation. However, little is known about recovery patterns in organisms exposed to organophosphates. The aim of the present work was to evaluate the recovery capacity (during 21 days in pesticide-free water) of cholinesterase activity and neurotoxicity in C. gibbosa after 48 h of exposure to azinphos-methyl. Also, lethality and carboxylesterase activity were registered during the recovery period. Regarding enzyme activities, after a 48-h exposure to 20 MUg L(-1) of azinphos-methyl, cholinesterases showed an inhibition of 85% with respect to control, while carboxylesterases were not affected. After 21 days in pesticide free water, cholinesterases continued to be inhibited (70%). Severe neurotoxicity signs were observed after exposure: 82% of the snails presented lack of adherence to vessels, 11% showed weak adherence, and 96% exhibited an abnormal protrusion of the head-foot region from shell. After 21 days in pesticide-free water, only 15% of the snails presented severe signs of neurotoxicity. However, during the recovery period significant lethality (30%) was registered in treated snails. C. gibbosa is a very sensitive organism to azinphos-methyl. These snails play an important role in the structure and function of aquatic food webs in this region. Thus, a decline of this species' population would probably have an impact on aquatic and non-aquatic communities. Our results show that C. gibbosa is a relevant sentinel species for studying exposure and effects of azinphos-methyl using behavioral and biochemical biomarkers. Neurotoxic behavioral signs are very sensitive, non-destructive biomarkers, which can be easily detected for about one week after acute exposure. Cholinesterse activity is a very useful biomarker showing a high sensitivity and a slow recovery capacity increasing the possibility to indirectly detect organophosphates for long periods after a contaminant event. PMID- 26364255 TI - Advances in systems biology--New trends and perspectives. PMID- 26364256 TI - Regional Hospital Collaboration and Outcomes in Medicare Heart Failure Patients: See You in 7. AB - OBJECTIVES: The objective of this study was to evaluate an interhospital collaborative approach to improve 7-day post-discharge follow-up (7dFU) rates and reduce 30-day readmissions in heart failure (HF) patients. BACKGROUND: Early post discharge follow-up after HF hospitalization is associated with lower 30-day readmission rates. METHODS: Observational analyses of Medicare HF patients discharged from 10 collaborating hospitals (CH) participating in the Southeast Michigan See You in 7 Collaborative were carried out. We compared pre intervention (May 1, 2011 to April 30, 2012) and intervention (May 1, 2012 to April 30, 2013) 7dFU rates, unadjusted 30-day readmissions, risk-standardized 30 day readmissions (RSRR), and Medicare payments in CH and Michigan nonparticipating hospitals (NPH). RESULTS: 7dFU rates increased but remained low in both groups (CH: 31.1% to 34.4%; p < 0.001; NPH: 30.2% to 32.6%; p <0.001). During the intervention period, unadjusted readmissions decreased significantly in both groups (CH: 29.0% to 27.3%; p <0.001; NPH: 26.4% to 25.8%, p = 0.004); mean RSRR decreased more in CH than in NPH (CH: 31.1% to 28.5%; p < 0.001; NPH: 26.7% to 26.1%, p = 0.02; p = 0.015 for intergroup comparisons). Findings were similar when CH outcomes were matched 1:1 with similar NPH outcomes. Combined Medicare payments for inpatient and 30 days of post-discharge care decreased by $182 in CH and by $63 in NPH (per eligible HF discharge). CONCLUSIONS: See You in 7 Collaborative participation was associated with significantly lower 30-day readmissions and Medicare payments in HF patients. Increases in 7dFU were modest, but associated processes aimed at this goal may have improved the transition from inpatient to outpatient care. Regional hospital collaboration to share best practices could potentially reduce HF readmissions and associated costs. PMID- 26364257 TI - Novel Interventional Therapies to Modulate the Autonomic Tone in Heart Failure. AB - Heart failure (HF) represents a significant and expanding public health burden associated with increasing prevalence and exponential growth in related health care costs. Contemporary advances in both pharmacological and nonpharmacological therapies have often been restricted in application and benefit. Given the critical role of the autonomic nervous system (ANS) in maintaining cardiovascular homeostasis in the failing heart, there has been increasing interest in the role of ANS modulation as a therapeutic modality in HF. In this review, we highlight the anatomy of the ANS and its role in the pathophysiology of HF, as well as metrics of its assessment. Given the limitations associated with pharmacological ANS modulation, including lack of specificity and medication intolerance, we focus in this review on contemporary nonpharmacological ANS modulation therapies. For each therapy-vagal nerve stimulation, carotid baroreceptor stimulation, spinal cord stimulation, and renal denervation-we review the rationale for modulation, pre-clinical and clinical assessments, as well as procedural considerations and limitations. We conclude by commenting on novel technologies and strategies for ANS modulation on the horizon. PMID- 26364258 TI - What's Harder: Seeing a Doctor or Reducing Readmissions? PMID- 26364259 TI - Recovery effect of phenylpropanoid glycosides from Magnolia obovata fruit on alloxan-induced pancreatic islet damage in zebrafish (Danio rerio). AB - Investigation of phytochemicals from Magnolia obovata fruit led to the isolation of three novel phenylpropanoid glycosides: obovatoside A-C (1-3) and two known phenylpropanoids, syringin (4) and pavonisol (5). The structures of 1-5 were determined by NMR, HRMS, IR and CD spectroscopic analyses. All compounds were evaluated for their effects on recovery from alloxan-induced pancreatic islet damage in zebrafish. All compounds increased the size of the injured pancreatic islet from 0.60- to 1.14-fold. Compounds 1 and 3-5 significantly increased glucose absorption in zebrafish. PMID- 26364260 TI - Assessing the contribution of the two protein disulfide isomerases PDIA1 and PDIA3 to cisplatin resistance. AB - Intracellular binding of cisplatin to non-DNA partners, such as proteins, has received increasing attention as an additional mode of action and as mechanism of resistance. We investigated two cisplatin-interacting isoforms of protein disulfide isomerase regarding their contribution to acquired cisplatin resistance using sensitive and resistant A2780/A2780cis ovarian cancer cells. Cisplatin cytotoxicity was assessed after knockdown of either protein disulfide isomerase family A member 1 (PDIA1) or protein disulfide isomerase family A member 3 (PDIA3). Whereas PDIA1 knockdown led to increased cytotoxicity in resistant A2780cis cells, PDIA3 knockdown showed no influence on cytotoxicity. Coincubation with propynoic acid carbamoyl methyl amide 31 (PACMA31), a PDIA1 inhibitor, resensitized A2780cis cells to cisplatin treatment. Determination of the combination index revealed that the combination of cisplatin and PACMA31 acts synergistically. Our results warrant further evaluation of PDIA1 as promising target for chemotherapy, and its inhibition by PACMA31 as a new therapeutic approach. PMID- 26364261 TI - The health gap: the challenge of an unequal world. PMID- 26364262 TI - Antiretroviral chemoprophylaxis: PROUD and pragmatism. PMID- 26364263 TI - Pre-exposure prophylaxis to prevent the acquisition of HIV-1 infection (PROUD): effectiveness results from the pilot phase of a pragmatic open-label randomised trial. AB - BACKGROUND: Randomised placebo-controlled trials have shown that daily oral pre exposure prophylaxis (PrEP) with tenofovir-emtricitabine reduces the risk of HIV infection. However, this benefit could be counteracted by risk compensation in users of PrEP. We did the PROUD study to assess this effect. METHODS: PROUD is an open-label randomised trial done at 13 sexual health clinics in England. We enrolled HIV-negative gay and other men who have sex with men who had had anal intercourse without a condom in the previous 90 days. Participants were randomly assigned (1:1) to receive daily combined tenofovir disoproxil fumarate (245 mg) and emtricitabine (200 mg) either immediately or after a deferral period of 1 year. Randomisation was done via web-based access to a central computer-generated list with variable block sizes (stratified by clinical site). Follow-up was quarterly. The primary outcomes for the pilot phase were time to accrue 500 participants and retention; secondary outcomes included incident HIV infection during the deferral period, safety, adherence, and risk compensation. The trial is registered with ISRCTN (number ISRCTN94465371) and ClinicalTrials.gov (NCT02065986). FINDINGS: We enrolled 544 participants (275 in the immediate group, 269 in the deferred group) between Nov 29, 2012, and April 30, 2014. Based on early evidence of effectiveness, the trial steering committee recommended on Oct 13, 2014, that all deferred participants be offered PrEP. Follow-up for HIV incidence was complete for 243 (94%) of 259 patient-years in the immediate group versus 222 (90%) of 245 patient-years in the deferred group. Three HIV infections occurred in the immediate group (1.2/100 person-years) versus 20 in the deferred group (9.0/100 person-years) despite 174 prescriptions of post-exposure prophylaxis in the deferred group (relative reduction 86%, 90% CI 64-96, p=0.0001; absolute difference 7.8/100 person-years, 90% CI 4.3-11.3). 13 men (90% CI 9-23) in a similar population would need access to 1 year of PrEP to avert one HIV infection. We recorded no serious adverse drug reactions; 28 adverse events, most commonly nausea, headache, and arthralgia, resulted in interruption of PrEp. We detected no difference in the occurrence of sexually transmitted infections, including rectal gonorrhoea and chlamydia, between groups, despite a suggestion of risk compensation among some PrEP recipients. INTERPRETATION: In this high incidence population, daily tenofovir-emtricitabine conferred even higher protection against HIV than in placebo-controlled trials, refuting concerns that effectiveness would be less in a real-world setting. There was no evidence of an increase in other sexually transmitted infections. Our findings strongly support the addition of PrEP to the standard of prevention for men who have sex with men at risk of HIV infection. FUNDING: MRC Clinical Trials Unit at UCL, Public Health England, and Gilead Sciences. PMID- 26364265 TI - Cannibalism stress response in Bacillus subtilis. AB - When faced with carbon source limitation, the Gram-positive soil organism Bacillus subtilis initiates a survival strategy called sporulation, which leads to the formation of highly resistant endospores that allow B. subtilis to survive even long periods of starvation. In order to avoid commitment to this energy demanding and irreversible process, B. subtilis employs another strategy called 'cannibalism' to delay sporulation as long as possible. Cannibalism involves the production and secretion of two cannibalism toxins, sporulation delaying protein (SDP) and sporulation killing factor (SKF), which are able to lyse sensitive siblings. The lysed cells are thought to then provide nutrients for the cannibals to slow down or even prevent them from entering sporulation. In this study, we uncovered the role of the cell envelope stress response (CESR), especially the Bce-like antimicrobial peptide detoxification modules, in the cannibalism stress response during the stationary phase. SDP and SKF specifically induce Bce-like systems and some extracytoplasmic function sigma factors in stationary-phase cultures, but only the latter provide some degree of protection. A full Bce response is only triggered by mature toxins, and not by toxin precursors. Our study provides insights into the close relationship between stationary-phase survival and the CESR of B. subtilis. PMID- 26364264 TI - Impaired respiratory function and heightened pulmonary inflammation in episodic binge ethanol intoxication and burn injury. AB - Clinical data indicate that cutaneous burn injuries covering greater than 10% of the total body surface area are associated with significant morbidity and mortality, in which pulmonary complications, including acute respiratory distress syndrome (ARDS), contribute to nearly half of all patient deaths. Approximately 50% of burn patients are intoxicated at the time of hospital admission, which increases days on ventilators by 3-fold, and doubles the length of hospitalization, compared to non-intoxicated burn patients. The most common drinking pattern in the United States is binge drinking, where an individual rapidly consumes alcoholic beverages (4 for women, 5 for men) in 2 h. An estimated 38 million Americans binge drink, often several times per month. Experimental data demonstrate that a single binge-ethanol exposure, prior to scald injury, impairs innate and adaptive immune responses, thereby enhancing infection susceptibility and amplifying pulmonary inflammation, neutrophil infiltration, and edema, and is associated with increased mortality. Since these characteristics are similar to those observed in ARDS burn patients, our study objective was to determine whether ethanol intoxication and burn injury and the subsequent pulmonary congestion affect physiological parameters of lung function, using non-invasive and unrestrained plethysmography in a murine model system. Furthermore, to mirror young adult binge-drinking patterns, and to determine the effect of multiple ethanol exposures on pulmonary inflammation, we utilized an episodic binge-ethanol exposure regimen, where mice were exposed to ethanol for a total of 6 days (3 days ethanol, 4 days rest, 3 days ethanol) prior to burn injury. Our analyses demonstrate mice exposed to episodic binge ethanol and burn injury have higher mortality, increased pulmonary congestion and neutrophil infiltration, elevated neutrophil chemoattractants, and respiratory dysfunction, compared to burn or ethanol intoxication alone. Overall, our study identifies plethysmography as a useful tool for characterizing respiratory function in a murine burn model and for future identification of therapeutic compounds capable of restoring pulmonary functionality. PMID- 26364266 TI - Medical image computing in diagnosis and intervention of spinal diseases. AB - Spinal image analysis and computer assisted intervention have emerged as new and independent research areas, due to the importance of treatment of spinal diseases, increasing availability of spinal imaging, and advances in analytics and navigation tools. Among others, multiple modality spinal image analysis and spinal navigation tools have emerged as two keys in this new area. We believe that further focused research in these two areas will lead to a much more efficient and accelerated research path, avoiding detours that exist in other applications, such as in brain and heart. PMID- 26364267 TI - Environmental risk assessment of acid rock drainage under uncertainty: The probability bounds and PHREEQC approach. AB - Acid rock drainage (ARD) is a major environmental problem that poses significant environmental risks during and after mining activities. A new methodology for environmental risk assessment based on probability bounds and a geochemical speciation model (PHREEQC) is presented. The methodology provides conservative and non-conservative ways of estimating risk of heavy metals posed to selected endpoints probabilistically, while propagating data and parameter uncertainties throughout the risk assessment steps. The methodology is demonstrated at a minesite located in British Columbia, Canada. The result of the methodology for the case study minesite shows the fate-and-transport of heavy metals is well simulated in the mine environment. In addition, the results of risk characterization for the case study show that there is risk due to transport of heavy metals into the environment. PMID- 26364268 TI - Assessment of the mechanisms involved in the removal of emerging contaminants by microalgae from wastewater: a laboratory scale study. AB - Aerated batch reactors (2.5L) fed either with urban or synthetic wastewater were inoculated with microalgae (dominated by Chlorella sp. and Scenedesmus sp.) to remove caffeine, ibuprofen, galaxolide, tributyl phosphate, 4-octylphenol, tris(2 chloroethyl) phosphate and carbamazepine for 10 incubation days. Non-aerated and darkness reactors were used as controls. Microalgae grew at a rate of 0.25 d(-1) with the complete removal of N-NH4 during the course of the experiment. After 10 incubation days, up to 99% of the microcontaminants with a Henry's law constant higher than 3 10(-1) Pa m(3) mol(-1) (i.e., 4-octylphenol, galaxolide, and tributyl phosphate) were removed by volatilization due to the effect of air stripping. Whereas biodegradation was effective for removing ibuprofen and caffeine, carbamazepine and tris(2-chloroethyl) phosphate behaved as recalcitrant compounds. The use of microalgae was proved to be relevant for increasing the biodegradation removal efficiency of ibuprofen by 40% and reducing the lag phase of caffeine by 3 days. Moreover, the enantioselective biodegradation of S ibuprofen suggested a biotic prevalent removal process, which was supported by the identification of carboxy-ibuprofen and hydroxy-ibuprofen. The results from microalgae reactors fed with synthetic wastewater showed no clear evidences of microalgae uptake of any of the studied microcontaminants. PMID- 26364269 TI - Determination of trace mercury in water based on N-octylpyridinium ionic liquids preconcentration and stripping voltammetry. AB - A novel method for determination of trace mercury in water is developed. The method is performed by extracting mercury firstly with ionic liquids (ILs) and then detecting the concentration of mercury in organic media with anodic stripping voltammetry. Liquid-liquid extraction of mercury(II) ions by four ionic liquids with N-octylpyridinium cations ([OPy](+)) was studied. N-octylpyridinium tetrafluoroborate and N-octylpyridinium trifluoromethylsulfonate were found to be efficient and selective extractant for mercury. Temperature controlled dispersive liquid phase microextraction (TC-DLPME) technique was utilized to improve the performance of preconcentration. After extraction, precipitated IL was diluted by acetonitrile buffer and mercury was detected by differential pulse stripping voltammetry (DPSV) with gold disc electrode. Mercury was enriched by 17 times while interfering ions were reduced by two orders of magnitude in the organic media under optimum condition. Sensitivity and selectivity for electrochemical determination of mercury were improved by using the proposed method. Tap, pond and waste water samples were analyzed with recoveries ranging from 81% to 107% and detection limit of 0.05 MUg/L. PMID- 26364270 TI - The consortium of heterogeneous cobalt phthalocyanine catalyst and bicarbonate ion as a novel platform for contaminants elimination based on peroxymonosulfate activation. AB - The design of catalytic oxidation processes with high efficiency has attracted considerable attention for a long while in environmental catalysis. In this work, a novel oxidation system, CFs-CoPc/PMS, was developed by coupling cellulosic fibers-bonded cobalt phthalocyanine (CFs-CoPc) with peroxymonosulfate (PMS). CFs CoPc/PMS system could effectively decolorize azo dyes such as Acid Red 1 (AR1) with almost 100% decolorization efficiency in 35 min, suggesting that the CFs CoPc/PMS system was a highly efficient oxidation process. In addition, bicarbonate ion (HCO3(-)) was further introduced to CFs-CoPc/PMS to construct a combined system, CFs-CoPc/PMS/HCO3(-). Remarkably, this system turned the negative effect of HCO3(-) observed in most reported Co/PMS systems into a positive one, which enhanced the AR1 decolorization with over 2-fold increase of the rate constant. The main factor responsible for the enhancement was high valent cobalt-oxo intermediates (PcCo(IV)=O), which was presumably generated via the heterolytic cleavage of the PMS OO bond by CoPc-HCO3(-) complex. It is noteworthy that high-valent cobalt-oxo intermediates as the major active species is different from most reported mechanisms in Co/PMS systems, in which hydroxyl and sulfate radicals are recognized as the dominant active species. This study paves an avenue for developing highly efficient catalytic oxidation technology for wastewater remediation. PMID- 26364271 TI - H7N9 influenza outbreak in China 2013: In silico analyses of conserved segments of the hemagglutinin as a basis for the selection of peptide vaccine targets. AB - The sudden emergence of a human infecting strain of H7N9 influenza virus in China in 2013 leading to fatalities in about 30% of the cases has caused wide concern that additional mutations in the strain leading to human to human transmission could lead to a deadly pandemic. It may happen in a short time span as the outbreak of H7N9 is more and more recurrent, which implies that H7N9 evolution is speeding up. H7N9 flu strains were not known to infect humans before this attack in China in February 2013 and it was solely an avian strain. While currently available drugs such as oseltamivir have been found to be largely effective against the H7N9, albeit with recent reported cases of development of resistance to the drug, there is a necessity to identify alternatives to combat this disease, especially if it assumes pandemic proportions. In our work, we have tried to investigate for the genetic changes in hemagglutinin (HA) protein sequence that lead to human infection by an avian infecting virus and identify possible peptide targets to design vaccines to control this upcoming risk. We identified three highly conserved regions in all H7 subtypes, of which one particular immunogenic surface exposed region was found to be well conserved in all human infecting H7N9 strains (accessed up to 27th March 2014). Compared to H7N9 avian strains, we identified two mutations in this conserved region at the receptor binding site of all post-February 2013 human-infecting H7N9China hemagglutinin protein sequences. One of the mutations is very close (3.6 A) to the hemagglutinin sialic acid binding pocket that may lead to better binding to human host's sialic acid due to the changes in hydrophobicity of the microenvironment of the binding site. We found that the peptide region with these mutational changes that are specific for human infecting H7N9 virus possess the possibility of being used as target for a peptide vaccine. PMID- 26364273 TI - Cortico-Striatal GABAergic and Glutamatergic Dysregulations in Subjects at Ultra High Risk for Psychosis Investigated with Proton Magnetic Resonance Spectroscopy. AB - BACKGROUND: Dysregulations of the major inhibitory and excitatory amino neurotransmitter systems of gamma-aminobutyric acid and glutamate, respectively, have been described in patients with schizophrenia. However, it is unclear whether these abnormalities are present in subjects at ultra-high risk for psychosis. METHODS: Twenty-three antipsychotic naive subjects at ultra-high risk and 24 healthy control subjects, matched for age, sex, handedness, cigarette smoking, and parental education, underwent proton magnetic resonance spectroscopy scans in the dorsal caudate bilaterally and the medial prefrontal cortex at 3T. Levels of gamma-aminobutyric acid and of the combined resonance of glutamate and glutamine (Glx) were obtained using the standard J-editing technique and expressed as peak area ratios relative to the synchronously acquired unsuppressed voxel water signal. RESULTS: Higher levels of gamma-aminobutyric acid (P<.001) and Glx (P=.007) were found in the dorsal caudate of the subjects at ultra-high risk than in the healthy controls. In the medial prefrontal cortex, likewise, both gamma-aminobutyric acid (P=.03) and Glx (P=.006) levels were higher in the ultra-high risk group than in the healthy controls. No group differences were found for any of the other metabolites (N-acetylaspartate, total choline, or total creatine) in the 2 regions of interest. CONCLUSIONS: This study presents the first evidence of abnormal elevations, in subjects at ultra-high risk, of gamma-aminobutyric acid and Glx in 2 brain regions that have been implicated in the pathophysiology of psychosis, warranting longitudinal studies to assess whether these neurotransmitter abnormalities can serve as noninvasive biomarkers of conversion risk to psychosis as well as of illness progression and treatment response. PMID- 26364274 TI - D-Cycloserine in Neuropsychiatric Diseases: A Systematic Review. AB - D-Cycloserine, known from tuberculosis therapy, has been widely introduced to neuropsychiatric studies, since its central active mechanism as a partial NMDA agonist has been found. In this review, we evaluate its therapeutic potential in neuropsychological disorders and discuss its pitfalls in terms of dosing and application frequency as well as its safety in low-dose therapy. Therefore, we identified 91 clinical trials by performing a Medline search. We demonstrate in part preliminary but increasing evidence that D-cycloserine may be effective in various psychiatric diseases, including schizophrenia, anxiety disorders, addiction, eating disorders, major depression, and autism as well as in neurological diseases, including dementia, Alzheimer's disease, and spinocerebellar degeneration. D-Cycloserine in low-dose therapy is safe, but there is still a need for new drugs with higher specificity to the different N methyl-D-aspartate-receptor subunits. PMID- 26364275 TI - Safety and Preliminary Efficacy of the Acetylcholinesterase Inhibitor Huperzine A as a Treatment for Cocaine Use Disorder. AB - BACKGROUND: Cholinergic transmission is altered by drugs of abuse and contributes to psychostimulant reinforcement. In particular, acetylcholinesterase inhibitors, like huperzine A, may be effective as treatments for cocaine use disorder. METHODS: The current report describes results from a double-blind, placebo controlled study in which participants (n=14-17/group) were randomized to huperzine A (0.4 or 0.8 mg) or placebo. Participants received randomized infusions of cocaine (0 and 40 mg, IV) on days 1 and 9. On day 10, participants received noncontingent, randomized infusions of cocaine (0 and 20mg, IV) before making 5 choices to receive additional infusions. RESULTS: Huperzine A was safe and well-tolerated and compared with placebo, treatment with huperzine A did not cause significant changes in any cocaine pharmacokinetic parameters (all P>.05). Time-course and peak effects analyses show that treatment with 0.4 mg of huperzine A significantly attenuated cocaine-induced increases of "Any Drug Effect," "High," "Stimulated," "Willing to Pay," and "Bad Effects" (all P>.05). CONCLUSIONS: The current study represents a significant contribution to the addiction field since it serves as the first published report on the safety and potential efficacy of huperzine A as a treatment for cocaine use disorder. PMID- 26364272 TI - Quantitative Proteomic Analysis Reveals Molecular Adaptations in the Hippocampal Synaptic Active Zone of Chronic Mild Stress-Unsusceptible Rats. AB - BACKGROUND: While stressful events are recognized as an important cause of major depressive disorder, some individuals exposed to life stressors maintain normal psychological functioning. The molecular mechanism(s) underlying this phenomenon remain unclear. Abnormal transmission and plasticity of hippocampal synapses have been implied to play a key role in the pathoetiology of major depressive disorder. METHODS: A chronic mild stress protocol was applied to separate susceptible and unsusceptible rat subpopulations. Proteomic analysis using an isobaric tag for relative and absolute quantitation coupled with tandem mass spectrometry was performed to identify differential proteins in enriched hippocampal synaptic junction preparations. RESULTS: A total of 4318 proteins were quantified, and 89 membrane proteins were present in differential amounts. Of these, SynaptomeDB identified 81 (91%) having a synapse-specific localization. The unbiased profiles identified several candidate proteins within the synaptic junction that may be associated with stress vulnerability or insusceptibility. Subsequent functional categorization revealed that protein systems particularly involved in membrane trafficking at the synaptic active zone exhibited a positive strain as potential molecular adaptations in the unsusceptible rats. Moreover, through STRING and immunoblotting analysis, membrane-associated GTP-bound Rab3a and Munc18-1 appear to coregulate syntaxin-1/SNAP25/VAMP2 assembly at the hippocampal presynaptic active zone of unsusceptible rats, facilitating SNARE mediated membrane fusion and neurotransmitter release, and may be part of a stress-protection mechanism in actively maintaining an emotional homeostasis. CONCLUSIONS: The present results support the concept that there is a range of potential protein adaptations in the hippocampal synaptic active zone of unsusceptible rats, revealing new investigative targets that may contribute to a better understanding of stress insusceptibility. PMID- 26364277 TI - Clarifying the Mechanisms of Antidepressants. PMID- 26364276 TI - S100B Serum Levels Predict Treatment Response in Patients with Melancholic Depression. AB - BACKGROUND: There is an ongoing search for biomarkers in psychiatry, for example, as diagnostic tools or predictors of treatment response. The neurotrophic factor S100 calcium binding protein B (S100B) has been discussed as a possible predictor of antidepressant response in patients with major depression, but also as a possible biomarker of an acute depressive state. The aim of the present study was to study the association of serum S100B levels with antidepressant treatment response and depression severity in melancholically depressed inpatients. METHODS: After a wash-out period of 1 week, 40 inpatients with melancholic depression were treated with either venlafaxine or imipramine. S100B levels and Hamilton Depression Rating Scale (HAM-D) scores were assessed at baseline, after 7 weeks of treatment, and after 6 months. RESULTS: Patients with high S100B levels at baseline showed a markedly better treatment response defined as relative reduction in HAM-D scores than those with low baseline S100B levels after 7 weeks (P=.002) and 6 months (P=.003). In linear regression models, S100B was a significant predictor for treatment response at both time points. It is of interest to note that nonresponders were detected with a predictive value of 85% and a false negative rate of 7.5%. S100B levels were not associated with depression severity and did not change with clinical improvement. CONCLUSIONS: Low S100B levels predict nonresponse to venlafaxine and imipramine with high precision. Future studies have to show which treatments are effective in patients with low levels of S100B so that this biomarker will help to reduce patients' burden of nonresponding to frequently used antidepressants. PMID- 26364278 TI - Mobility Outcomes Following Five Training Sessions with a Powered Exoskeleton. AB - BACKGROUND: Loss of legged mobility due to spinal cord injury (SCI) is associated with multiple physiological and psychological impacts. Powered exoskeletons offer the possibility of regained mobility and reversal or prevention of the secondary effects associated with immobility. OBJECTIVE: This study was conducted to evaluate mobility outcomes for individuals with SCI after 5 gait-training sessions with a powered exoskeleton, with a primary goal of characterizing the ease of learning and usability of the system. METHODS: Sixteen subjects with SCI were enrolled in a pilot clinical trial at Shepherd Center, Atlanta, Georgia, with injury levels ranging from C5 complete to L1 incomplete. An investigational Indego exoskeleton research kit was evaluated for ease of use and efficacy in providing legged mobility. Outcome measures of the study included the 10-meter walk test (10 MWT) and the 6-minute walk test (6 MWT) as well as measures of independence including donning and doffing times and the ability to walk on various surfaces. RESULTS: At the end of 5 sessions (1.5 hours per session), average walking speed was 0.22 m/s for persons with C5-6 motor complete tetraplegia, 0.26 m/s for T1-8 motor complete paraplegia, and 0.45 m/s for T9-L1 paraplegia. Distances covered in 6 minutes averaged 64 meters for those with C5 6, 74 meters for T1-8, and 121 meters for T9-L1. Additionally, all participants were able to walk on both indoor and outdoor surfaces. CONCLUSIONS: Results after only 5 sessions suggest that persons with tetraplegia and paraplegia learn to use the Indego exoskeleton quickly and can manage a variety of surfaces. Walking speeds and distances achieved also indicate that some individuals with paraplegia can quickly become limited community ambulators using this system. PMID- 26364279 TI - Assessment of In-Hospital Walking Velocity and Level of Assistance in a Powered Exoskeleton in Persons with Spinal Cord Injury. AB - BACKGROUND: Individuals with spinal cord injury (SCI) often use a wheelchair for mobility due to paralysis. Powered exoskeletal-assisted walking (EAW) provides a modality for walking overground with crutches. Little is known about the EAW velocities and level of assistance (LOA) needed for these devices. OBJECTIVE: The primary aim was to evaluate EAW velocity, number of sessions, and LOA and the relationships among them. The secondary aims were to report on safety and the qualitative analysis of gait and posture during EAW in a hospital setting. METHODS: Twelve individuals with SCI >= 1.5 years who were wheelchair users participated. They wore a powered exoskeleton (ReWalk; ReWalk Robotics, Inc., Marlborough, MA) with Lofstrand crutches to complete 10-meter (10 MWT) and 6 minute (6MWT) walk tests. LOA was defined as modified independence (MI), supervision (S), minimal assistance (Min), and moderate assistance (Mod). Best effort EAW velocity, LOA, and observational gait analysis were recorded. RESULTS: Seven of 12 participants ambulated >= 0.40 m/s. Five participants walked with MI, 3 with S, 3 with Min, and 1 with Mod. Significant inverse relationships were noted between LOA and EAW velocity for both 6 MWT (Z value = 2.63, Rho = 0.79, P = .0086) and 10 MWT (Z value = 2.62, Rho = 0.79, P = .0088). There were 13 episodes of mild skin abrasions. MI and S groups ambulated with 2-point alternating crutch pattern, whereas the Min and Mod groups favored 3-point crutch gait. CONCLUSIONS: Seven of 12 individuals studied were able to ambulate at EAW velocities >= 0.40 m/s, which is a velocity that may be conducive to outdoor activity-related community ambulation. The ReWalk is a safe device for in hospital ambulation. PMID- 26364280 TI - Time and Effort Required by Persons with Spinal Cord Injury to Learn to Use a Powered Exoskeleton for Assisted Walking. AB - BACKGROUND: Powered exoskeletons have been demonstrated as being safe for persons with spinal cord injury (SCI), but little is known about how users learn to manage these devices. OBJECTIVE: To quantify the time and effort required by persons with SCI to learn to use an exoskeleton for assisted walking. METHODS: A convenience sample was enrolled to learn to use the first-generation Ekso powered exoskeleton to walk. Participants were given up to 24 weekly sessions of instruction. Data were collected on assistance level, walking distance and speed, heart rate, perceived exertion, and adverse events. Time and effort was quantified by the number of sessions required for participants to stand up, walk for 30 minutes, and sit down, initially with minimal and subsequently with contact guard assistance. RESULTS: Of 22 enrolled participants, 9 screen-failed, and 7 had complete data. All of these 7 were men; 2 had tetraplegia and 5 had motor-complete injuries. Of these, 5 participants could stand, walk, and sit with contact guard or close supervision assistance, and 2 required minimal to moderate assistance. Walk times ranged from 28 to 94 minutes with average speeds ranging from 0.11 to 0.21 m/s. For all participants, heart rate changes and reported perceived exertion were consistent with light to moderate exercise. CONCLUSIONS: This study provides preliminary evidence that persons with neurological weakness due to SCI can learn to walk with little or no assistance and light to somewhat hard perceived exertion using a powered exoskeleton. Persons with different severities of injury, including those with motor complete C7 tetraplegia and motor incomplete C4 tetraplegia, may be able to learn to use this device. PMID- 26364281 TI - Acute Cardiorespiratory and Metabolic Responses During Exoskeleton-Assisted Walking Overground Among Persons with Chronic Spinal Cord Injury. AB - BACKGROUND: Lower extremity robotic exoskeleton technology is being developed with the promise of affording people with spinal cord injury (SCI) the opportunity to stand and walk. The mobility benefits of exoskeleton-assisted walking can be realized immediately, however the cardiorespiratory and metabolic benefits of this technology have not been thoroughly investigated. OBJECTIVE: The purpose of this pilot study was to evaluate the acute cardiorespiratory and metabolic responses associated with exoskeleton-assisted walking overground and to determine the degree to which these responses change at differing walking speeds. METHODS: Five subjects (4 male, 1 female) with chronic SCI (AIS A) volunteered for the study. Expired gases were collected during maximal graded exercise testing and two, 6-minute bouts of exoskeleton-assisted walking overground. Outcome measures included peak oxygen consumption (VO2peak), average oxygen consumption (VO2avg), peak heart rate (HRpeak), walking economy, metabolic equivalent of tasks for SCI (METssci), walk speed, and walk distance. RESULTS: Significant differences were observed between walk-1 and walk-2 for walk speed, total walk distance, VO2avg, and METssci. Exoskeleton-assisted walking resulted in %VO2peak range of 51.5% to 63.2%. The metabolic cost of exoskeleton-assisted walking ranged from 3.5 to 4.3 METssci. CONCLUSIONS: Persons with motor-complete SCI may be limited in their capacity to perform physical exercise to the extent needed to improve health and fitness. Based on preliminary data, cardiorespiratory and metabolic demands of exoskeleton-assisted walking are consistent with activities performed at a moderate intensity. PMID- 26364282 TI - Lower Extremity Strength Is Correlated with Walking Function After Incomplete SCI. AB - BACKGROUND: Lower extremity strength has been reported to relate to walking ability, however, the relationship between voluntary lower extremity muscle function as measured by isokinetic dynamometry and walking have not been thoroughly examined in individuals with incomplete spinal cord injury (iSCI). OBJECTIVE: To determine the extent to which measures of maximal voluntary isometric contraction (MVIC) and rate of torque development (RTD) in the knee extensor (KE) and plantar flexor (PF) muscle groups correlate with self-selected overground walking speed and spatiotemporal characteristics of walking. METHODS: Twenty-two subjects with chronic (>6 months) iSCI participated in a cross sectional study. Values for MVIC and RTD in the KE and PF muscle groups were determined by isokinetic dynamometry. Walking speed and spatiotemporal characteristics of walking were measured during overground walking. RESULTS: MVIC in the KE and PF muscle groups correlated significantly with walking speed. RTD was significantly correlated with walking speed in both muscle groups, the more involved PF muscle group showing the strongest correlation with walking speed (r = 0.728). RTD in the KE and PF muscle groups of the more-involved limb was significantly correlated with single support time of the more-involved limb. CONCLUSIONS: These data demonstrate that lower extremity strength is associated with walking ability after iSCI. Correlations for the muscle groups of the move involved side were stronger compared to the less-involved limb. In addition, PF function is highlighted as a potential limiting factor to walking speed along with the importance of RTD. PMID- 26364283 TI - Energy Cost of Lower Body Dressing, Pop-Over Transfers, and Manual Wheelchair Propulsion in People with Paraplegia Due to Motor-Complete Spinal Cord Injury. AB - BACKGROUND: Energy required for able-bodied individuals to perform common activities is well documented, whereas energy associated with daily activities among people with spinal cord injury (SCI) is less understood. OBJECTIVE: To determine energy expended during several basic physical tasks specific to individuals with paraplegia due to motor-complete SCI. METHODS: Sixteen adults with motor-complete SCI below T2 level and duration of paraplegia greater than 3 months were included. Oxygen consumption (VO2), caloric expenditure, and heart rate were measured at rest and while participants performed lower body dressing (LBD), pop-over transfers (POTs), and manual wheelchair propulsion (MWP) at a self-selected pace. These data were used to calculate energy expenditure in standard metabolic equivalents (METs), as defined by 1 MET = 3.5 mL O2/kg/min, and in SCI METs using the conversion 1 SCI MET = 2.7 mL O2/kg/min. RESULTS: VO2 at rest was 3.0 +/- 0.9 mL O2/kg/min, which equated to 0.9 +/- 0.3 standard METs and 1.1 +/- 0.4 SCI METs in energy expenditure. LBD required 3.2 +/- 0.7 METs and 4.1 +/- 0.9 SCI METs; POTs required 3.4 +/- 1.0 METs and 4.5 +/- 1.3 SCI METs; and MWP required 2.4 +/- 0.6 METs and 3.1 +/- 0.7 SCI METs. CONCLUSIONS: Resting VO2 for adults with motor-complete paraplegia is 3.0 mL O2/kg/min, which is lower than standard resting VO2 in able-bodied individuals. Progressively more energy is required to perform MWP, LBD, and POTs, respectively. Use of the standard METs formula may underestimate the level of intensity an individual with SCI uses to perform physical activities. PMID- 26364284 TI - Depression Following Spinal Cord Injury: Its Relationship to Demographic and Socioeconomic Indicators. AB - BACKGROUND: Depression is a common psychological problem that decreases life satisfaction and quality of life in people with spinal cord injury (SCI). OBJECTIVE: The aim of this study was to investigate the prevalence of depression after SCI and its association with pathophysiological, demographic, and socioeconomic factors, including sex, age, level of injury, financial status, and suicidal thoughts. METHODS: This was a cross-sectional study of 134 adults (>= 18 years old) with SCI who were referred to the Brain and Spinal Cord Injury Research Center (BASIR) clinic, Tehran University of Medical Sciences, for outpatient rehabilitation. The Beck Depression Inventory (BDI-II Persian), a 21 question multiple-choice inventory, was used to measure the presence and severity of depression. Data were collected by interview. RESULTS: Sixty-six (49.3%) participants had mild to severe depression. There was a higher probability of depression in individuals with SCI who were female, had tetraplegia, had suicidal thoughts, had a history of suicide attempt, had a low education level, or were taken cared for by a family member other than a spouse or parents. CONCLUSIONS: Depression was highly prevalent in individuals with SCI and was related to some demographic, pathophysiological, and socioeconomic indicators. The primary predictive indicators and the factors influencing depression should be determined to provide early detection and timely treatment to prevent more complications and improve quality of life for individuals with SCI. PMID- 26364285 TI - Effects of Adult Romantic Attachment and Social Support on Resilience and Depression in Individuals with Spinal Cord Injuries. AB - BACKGROUND: Spinal cord injury (SCI) can cause psychological consequences that negatively affect quality of life. It is increasingly recognized that factors such as resilience and social support may produce a buffering effect and are associated with improved health outcomes. However the influence of adult attachment style on an individual's ability to utilize social support after SCI has not been examined. OBJECTIVE: The purpose of this study was to examine relationships between adult romantic attachment perceived social support depression and resilience in individuals with SCI. In addition we evaluated potential mediating effects of social support and adult attachment on resilience and depression. METHODS: Participants included 106 adults with SCI undergoing inpatient rehabilitation. Individuals completed measures of adult attachment (avoidance and anxiety) social support resilience and depression. Path analysis was performed to assess for presence of mediation effects. RESULTS: When accounting for the smaller sample size support was found for the model (comparative fit index = .927; chi square = 7.86, P = .01; beta = -0.25, standard error [SE] = -2.93, P < .05). The mediating effect of social support on the association between attachment avoidance and resilience was the only hypothesized mediating effect found to be significant (beta = -0.25, SE = -2.93, P < .05). CONCLUSIONS: Results suggest that individuals with SCI with higher levels of attachment avoidance have lower perceived social support which relates to lower perceived resilience. Assessing attachment patterns during inpatient rehabilitation may allow therapists to intervene to provide greater support. PMID- 26364286 TI - Antidepressants Are Effective in Decreasing Neuropathic Pain After SCI: A Meta Analysis. AB - OBJECTIVE: To systematically review and assess the effectiveness and safety of antidepressants for neuropathic pain among individuals with spinal cord injury (SCI). METHODS: A systematic search was conducted using multiple databases for relevant articles published from 1980 to April 2014. Randomized controlled trials (RCTs) involving antidepressant treatment of neuropathic pain with >= 3 individuals and >= 50% of study population with SCI were included. Two independent reviewers selected studies based on inclusion criteria and then extracted data. Pooled analysis using Cohen's d to calculate standardized mean difference, standard error, and 95% confidence interval for primary (pain) and other secondary outcomes was conducted. RESULTS: Four RCTs met inclusion criteria. Of these, 2 studies assessed amitriptyline, 1 trazadone, and 1 duloxetine among individuals with neuropathic SCI pain. A small effect was seen in the effectiveness of antidepressants in decreasing pain among individuals with SCI (standardized mean difference = 0.34 +/- 0.15; 95% CI, 0.05-0.62; P = .02). A number needed to treat of 3.4 for 30% or more pain relief was found by pooling 2 studies. Of these, significantly higher risk of experiencing constipation (risk ratio [RR] = 1.74; 95% CI, 1.09-2.78; P = .02) and dry mouth (RR = 1.39; 95% CI, 1.04-1.85; P = .02) was found amongst individuals receiving antidepressant treatment compared to those in the control group. CONCLUSIONS: The current meta analysis demonstrates that antidepressants are effective in reducing neuropathic SCI pain. However, this should be interpreted with caution due to the limited number of studies. Further evaluation of long-term therapeutic options may be required. PMID- 26364287 TI - Protection and Repair After Spinal Cord Injury: Accomplishments and Future Directions. AB - It was an honor for me to present the 2014 G. Heiner Sell Memorial Lecture at the annual American Spinal Injury Association (ASIA) meeting in San Antonio. For this purpose, I provided a comprehensive review of the scope of research targeting discovery and translational and clinical investigations into spinal cord injury (SCI) research. Indeed, these are exciting times in the area of spinal cord research and clinical initiatives. Many laboratories and clinical programs throughout the world are publishing data related to the pathophysiology of SCI and new strategies for protecting and promoting recovery in both animal models and humans. For this lecture, several topics were discussed including neuroprotective and reparative strategies, neurorehabilitation, quality of life issues, and future directions. In the area of neuroprotection, pathophysiological events that may be targeted with therapeutic strategies, including pharmacological and targeted temperature management were reviewed. For reparative approaches, the importance of both intrinsic and extrinsic mechanisms of axonal regeneration was highlighted. Various cell therapies currently being tested in preclinical and clinical arenas were reviewed as well as ongoing US Food and Drug Administration approved trials for SCI patients. Neurorehabilitation is an evolving research field with locomotive training strategies, electrical stimulation, and brain-machine interface programs targeting various types of SCI. The importance of testing combination approaches including neuroprotective, reparative, and rehabilitative strategies to maximize recovery mechanisms was therefore emphasized. Finally, quality of life issues that affect thousands of individuals living with paralysis were also presented. Future directions and specific obstacles that require attention as we continue to move the SCI field forward were discussed. PMID- 26364288 TI - Stopping or continuing clopidogrel 12 months after drug-eluting stent placement: the OPTIDUAL randomized trial. AB - AIM: This open-label, randomized, and multicentre trial tested the hypothesis that, on a background of aspirin, continuing clopidogrel would be superior to stopping clopidogrel at 12 months following drug-eluting stent (DES) implantation. METHODS AND RESULTS: Patients (N = 1799) who had undergone placement of >=1 DES for stable coronary artery disease or acute coronary syndrome were included in 58 French sites (January 2009-January 2013). Patients (N = 1385) free of major cardiovascular/cerebrovascular events or major bleeding and on aspirin and clopidogrel 12 months after stenting were eligible for randomization (1:1) between continuing clopidogrel 75 mg daily (extended-dual antiplatelet therapy, DAPT, group) or discontinuing clopidogrel (aspirin group). The primary outcome was net adverse clinical events defined as the composite of death, myocardial infarction, stroke, or major bleeding. Follow-up was planned from a minimum of 6 to a maximum of 36 months after randomization. Owing to slow recruitment, the study was stopped after enrolment of 1385 of a planned 1966 patients. Median follow-up after stenting was 33.4 months. The primary outcome occurred in 40 patients (5.8%) in the extended-DAPT group and 52 in the aspirin group (7.5%; hazard ratio 0.75, 95% confidence interval 0.50-1.28; P = 0.17). Rates of death were 2.3% in the extended-DAPT group and 3.5% in the aspirin group (HR 0.65, 95% CI 0.34-1.22; P = 0.18). Rates of major bleeding were identical (2.0%, P = 0.95). CONCLUSIONS: Extended DAPT did not achieve superiority in reducing net adverse clinical events compared to 12 months of DAPT after DES placement. The power of the OPTIDUAL trial was however low and reduced by premature termination of enrolment. CLINICALTRIALSGOV NUMBER: NCT00822536. PMID- 26364289 TI - Coronary microvascular obstruction in acute myocardial infarction. AB - The success of a primary percutaneous intervention (PCI) in the setting of ST elevation myocardial infarction depends on the functional and structural integrity of coronary microcirculation. Coronary microvascular dysfunction and obstruction (CMVO) occurs in up to half of patients submitted to apparently successful primary PCI and is associated to a much worse outcome. The current review summarizes the complex mechanisms responsible for CMVO, including pre existing coronary microvascular dysfunction, and highlights the current limitations in the assessment of microvascular function. More importantly, at the light of the substantial failure of trials hitherto published on the treatment of CMVO, this review proposes a novel integrated therapeutic approach, which should overcome the limitations of previous studies. PMID- 26364290 TI - Who are the real bird brains? Qualitative differences in behavioral flexibility between dogs (Canis familiaris) and pigeons (Columba livia). AB - Pigeons given a simultaneous spatial discrimination reversal, in which a single reversal occurs at the midpoint of each session, consistently show anticipation prior to the reversal as well as perseveration after the reversal, suggesting that they use a less effective cue (time or trial number into the session) than what would be optimal to maximize reinforcement (local feedback from the most recent trials). In contrast, rats (Rattus norvegicus) and humans show near optimal reversal learning on this task. To determine whether this is a general characteristic of mammals, in the present research, pigeons (Columba livia) and dogs (Canis familiaris) were tested with a simultaneous spatial discrimination mid-session reversal. Overall, dogs performed the task more poorly than pigeons. Interestingly, both pigeons and dogs employed what resembled a timing strategy. However, dogs showed greater perseverative errors, suggesting that they may have relatively poorer working memory and inhibitory control with this task. The greater efficiency shown by pigeons with this task suggests they are better able to time and use the feedback from their preceding choice as the basis of their future choice, highlighting what may be a qualitative difference between the species. PMID- 26364291 TI - Validation of an Ultrasound Cardiac Output Monitor as a Bedside Tool for Pediatric Patients. AB - The aim of our study was to determine the validity of cardiac output (CO) measurements taken with the ultrasonic cardiac output monitor (USCOM) by comparing to CO measured by pulmonary arterial catheter (PAC) thermodilution during cardiac catheterization. We enrolled thirty-one children (<18 years) undergoing cardiac catheterization in this double-blinded, prospective, observational study. The median CO measured by USCOM was 4.37 L/min (IQR 3.73, 5.60 L/min) compared to 4.28 L/min (IQR 3.52, 5.26 L/min) by PAC thermodilution. The bias (mean difference) between the two methods was 0.2 L/min, and the 95% limits of agreement were -1.2 to 1.6 L/min. The mean percentage error of CO between USCOM and PAC thermodilution was 11%. When excluding a sole outlier, the bias between the two measures decreased to 0.1 L/min (95% limits of agreement 0.6 to 0.9 L/min), and the percentage error was reduced to 8%. The median SVRI measured by USCOM was 22.0 Wood Units (IQR 17.0, 26.8 Wood Units) compared to 22.1 Wood Units (IQR 17.6, 27.4 Wood Units) by PAC thermodilution. Bias (mean difference) between the two methods was -0.6 Wood Units, and the 95% limits of agreement were -8.2 to 6.9 Wood Units. We found that the estimation of CO and by extension SVRI with USCOM is reliable against pulmonary artery catheter thermodilution in children with normal cardiac anatomy. Given the noninvasive nature of USCOM, speed of measurement, and relative ease of use, it may be useful as a bedside tool for pediatric patients. PMID- 26364292 TI - Yamadazyma riverae sp. nov., a yeast species isolated from plant materials. AB - Nine strains of a novel yeast species were isolated from rotting wood, tree bark, ant nests or living as endophytes in leaves of Vellozia gigantea. Analysis of the sequences of the internal transcribed spacer (ITS) region and the D1/D2 domains of the large subunit rRNA gene showed that this species was related to Candida insectorum in the Yamadazyma clade. The novel species differed from closely related species by 10 and 11 substitutions in the ITS region and the D1/D2 domains of the large subunit of the rRNA gene, respectively. The species is heterothallic and forms asci with one to two hat-shaped ascospores. The name Yamadazyma riverae sp. nov. is proposed for the novel species. The type strain is UFMG-CM-Y444T ( = CBS 14121T) and the allotype strain is TT12 ( = CBS 14098 = UFMG-CM-Y577). The Mycobank number is MB 813221. PMID- 26364293 TI - Titrating the Cost of Plant Toxins Against Predators: a Case Study with Common Duikers, Sylvicapra grimmia. AB - Foragers face many variables that influence their food intake. These may include habitat structure, time, climate, resource characteristic, food quality, and plant defenses. I conducted foraging experiments using common duikers that involved: 1) testing the effect of plant toxins on foraging, and 2) titrating toxin intake against safety. I used giving up densities (GUDs, food remaining after foraging) to test for selection among trays containing alfalfa pellets treated with water, with 10% oxalic acid, or 10% quebracho tannin. Pairs of trays were placed within islands of woody vegetation and out in open grass. I also conducted a titration experiment by offering the duikers a choice between a patch with water-treated pellets placed at a risky site, or a patch with one of three oxalic acid-treated pellets at a safe site. This made it possible to determine the concentration of oxalic acid at which the cost of toxin in the safe site equals the predation cost at the risky site. The common duikers showed no selectivity among the three treatments at 10% concentration, however, GUDs in the open grass (i.e., safe) were significantly lower than in the wooded islands (i.e., risky). As the oxalic acid concentration increased at the safe sites, the duiker's food intake from the risky sites increased significantly. The results demonstrate that foraging hazards may come in different forms such as predation and plant toxins, and their interactions may alter habitat use, foraging patterns, and perceptions of risk. These variables occur under natural situations, altering the overall habitat quality. PMID- 26364294 TI - Highly Potent Extracts from Pea (Pisum sativum) and Maize (Zea mays) Roots Can Be Used to Induce Quiescence in Entomopathogenic Nematodes. AB - Root exudates can play an important role in plant-nematode interactions. Recent studies have shown that the root cap exudates obtained from several plant species trigger a state of dormancy or quiescence in various genera of nematodes. This phenomenon is not only of fundamental ecological interest, but also has application potential if the plant-produced compound(s) could be used to control harmful nematodes or help to prolong the shelf-life of beneficial entomopathogenic nematodes (EPNs). The identification of the compound(s) involved in quiescence induction has proven to be a major challenge and requires large amounts of active material. Here, we present a high-throughput method to obtain bioactive root extracts from flash-frozen root caps of green pea and maize. The root cap extract obtained via this method was considerably more potent in inducing quiescence than exudate obtained by a previously used method, and consistently induced quiescence in the EPN Heterorhabditis megidis, even after a 30-fold dilution. Extracts obtained from the rest of the root were equally effective in inducing quiescence. Infective juveniles (IJs) of H. megidis exposed to these extracts readily recovered from their quiescent state as soon as they were placed in moist soil, and they were at least as infectious as the IJs that had been stored in water. Excessive exposure of IJs to air interfered with the triggering of quiescence. The implications of these results and the next steps towards identification of the quiescence-inducing compound(s) are discussed from the perspective of applying EPN against soil-dwelling insect pests. PMID- 26364295 TI - Phenolic Compounds and Their Fates In Tropical Lepidopteran Larvae: Modifications In Alkaline Conditions. AB - Lepidopteran larvae encounter a variety of phenolic compounds while consuming their host plants. Some phenolics may oxidize under alkaline conditions prevailing in the larval guts, and the oxidation products may cause oxidative stress to the larvae. In this study, we aimed to find new ways to predict how phenolic compounds may be modified in the guts of herbivorous larvae. To do so, we studied the ease of oxidation of phenolic compounds from 12 tropical tree species. The leaf extracts were incubated in vitro in alkaline conditions, and the loss of total phenolics during incubation was used to estimate the oxidizability of extracts. The phenolic profiles of the leaf extracts before and after incubation were compared, revealing that some phenolic compounds were depleted during incubation. The leaves of the 12 tree species were each fed to 12 species of lepidopteran larvae that naturally feed on these trees. The phenolic profiles of larval frass were compared to those of in vitro incubated leaf extracts. These comparisons showed that the phenolic profiles of alkali-treated samples and frass samples were similar in many cases. This suggested that certain phenolics, such as ellagitannins, proanthocyanidins, and galloylquinic acid derivatives were modified by the alkaline pH of the larval gut. In other cases, the chromatographic profiles of frass and in vitro incubated leaf extracts were not similar, and new modifications of phenolics were detected in the frass. We conclude that the actual fates of phenolics in vivo are often more complicated than can be predicted by a simple in vitro method. PMID- 26364296 TI - Economic impact of 21-gene recurrence score testing on early-stage breast cancer in Ireland. AB - The 21-gene test is a validated multi-gene diagnostic test that predicts chemotherapy (CT) benefit in oestrogen receptor positive (ER+), lymph node negative (N0) breast cancer (BC) patients (pts). Ireland was the first public health care system to reimburse this test in Europe. Study objectives were to assess the impact of this test on decision-making and to analyse the economic impact of testing. Between October 2011 and February 2013, a national, retrospective, cross-sectional observational study of ER+, N0 BC pts tested with the 21-gene test was conducted. Surveyed breast medical oncologists, provided the assumption for the decision impact analysis that grade (G) 1 pts would not have received CT before testing and G2/3 pts would have received CT before testing. Descriptive statistical analyses were performed. 592 pts were identified; Low, intermediate and high recurrence score were identified in 53, 36 and 10 % pts, respectively. 384 (70 %) pts had G2, 129 (22 %) G3 and 76 (13 %) G1 tumours. Post testing, 345 pts (59 %) experienced a change in CT decision; 339 changed to hormone therapy alone and 6 advised to receive CT. 172 (30 %) pts received CT, 12 (3.9 %) of pts with low scores, 108 (50.9 %) of intermediate risk and 50 (90.9 %) of pts with high risk scores. Net reduction in CT use was 58 % and net savings achieved were ?793,565. Since public reimbursement, the introduction of the 21 gene test has resulted in a significant reduction in chemotherapy administration and cost savings for the Irish public healthcare system. PMID- 26364297 TI - Adiposity is associated with p53 gene mutations in breast cancer. AB - Mutations in the p53 gene are among the most frequent genetic events in human cancer and may be triggered by environmental and occupational exposures. We examined the association of clinical and pathological characteristics of breast tumors and breast cancer risk factors according to the prevalence and type of p53 mutations. Using tumor blocks from incident cases from a case-control study in western New York, we screened for p53 mutations in exons 2-11 using the Affymetrix p53 Gene Chip array and analyzed case-case comparisons using logistic regression. The p53 mutation frequency among cases was 28.1 %; 95 % were point mutations (13 % of which were silent) and the remainder were single base pair deletions. Sixty seven percent of all point mutations were transitions; 24 % of them are G:C>A:T at CpG sites. Positive p53 mutation status was associated with poorer differentiation (OR, 95 % CI 2.29, 1.21-4.32), higher nuclear grade (OR, 95 % CI 1.99, 1.22-3.25), and increased Ki-67 status (OR, 95 % CI 1.81, 1.10 2.98). Cases with P53 mutations were more likely to have a combined ER-positive and PR-negative status (OR, 95 % CI 1.65, 1.01-2.71), and a combined ER-negative and PR-negative status (OR, 95 % CI 2.18, 1.47-3.23). Body mass index >30 kg/m(2), waist circumference >79 cm, and waist-to-hip ratio >0.86 were also associated with p53 status; obese breast cancer cases are more likely to have p53 mutations (OR, 95 % CI 1.78, 1.19-2.68). We confirmed that p53 mutations are associated with less favorable tumor characteristics and identified an association of p53 mutation status and adiposity. PMID- 26364298 TI - Preparation and experimental research into retrievable rapamycin- and heparin coated vena cava filters: a pilot study. AB - The use of retrievable vena cava filters (RVCFs) was once commonplace, but filter retrieval was often very difficult. Most unsuccessful retrieval was due to intimal hyperplasia of the inferior vena cava and in-filter thrombosis. This pilot study aimed to design a drug-eluting RVCF. The hypothesis was that coated drugs could be released continuously to inhibit vena intimal hyperplasia and thrombosis, and thus improve the retrieval rates of RVCFs. Various concentrations of polycaprolactone (PCL)/chloroform solution were made from a mixture of Rapamycin and Heparin according to the quality of PCL. The drug was coated onto the surface of the filters by a process of dipping. In vitro tests were performed to check stability and in vitro drug release. Animals receiving filter implantation were divided into 4 groups, the experimental intervention group (EI), experimental laparotomy group (EL), control intervention group (CI), and control laparotomy group (CL). Filters were retrieved by laparotomy in the EL and CL groups, and by interventional operation in the EI and CI groups at 10, 20 and 30 days after implantation. Pathological endothelia biopsies were performed with wood grain-eosin (HE) staining and immunohistochemical examination, with the proliferating cell nuclear antigen (PCNA) index, and the results were compared between the experimental and control groups. The weight of thrombus within the filters was also measured by scale and compared. The coating concentration that succeeded in completely covering the surface was 0.2 g/ml. There was better coverage by SEM at this concentration, and the coated drugs had no obvious loss after filter release. The drug release curves showed that the amount of Heparin released was more than 50 % at day 1; Rapamycin released little in the first few days, beginning in earnest at 20 to 30 days. The filters were easy to retrieve at 10 days for both groups, while neither could be retrieved at 30 days. However, at 20 days the filter in the EI group could be retrieved with some difficulty, but the filter in the CI group couldn't be removed at all. The pathological examination and immunohistochemical PCNA examination results showed that the use of drug-eluting filters could effectively inhibit endothelial hyperplasia at 10 and 20 days, but was less effective at 30 days. There was no apparent difference in the total weight of blood clots between the experimental and control groups. We successfully conducted a pilot study into preparing Rapamycin- and Heparin coated RVCFs. In vitro and in vivo tests further proved the possibility of improving the retrieval rates of RVCFs by effectively inhibiting vein endothelial proliferation, but the anticoagulation and antithrombosis effects of Heparin were unsatisfactory. PMID- 26364299 TI - Subcutaneous emphysema and pneumomediastinum following cocaine inhalation: a case report. AB - INTRODUCTION: Subcutaneous emphysema or pneumomediastinum can occur as a complication of illicit drug use although this is rare. When occurring without a pneumothorax and spontaneously, it is usually treated conservatively, but can have serious consequences. CASE PRESENTATION: Here, we present the case of an otherwise healthy 23-year-old Caucasian man who presented to the Emergency Department at our institution and was found to have both subcutaneous emphysema and pneumomediastinum as a result of cocaine use. His only presenting symptom was mild chest pain and he had palpable subcutaneous crepitations. He underwent a series of investigations including a chest radiograph and computed tomography as well as a barium fluoroscopy study to rule out secondary pneumomediastinum, which can be fatal. There were no other pulmonary features of illicit drug use, such as granulomas or fibrosis, seen on radiological imaging. He was subsequently managed with a period of observation and supportive care. CONCLUSION: We report a rare case of subcutaneous emphysema and pneumomediastinum likely due to the nasal insufflation of cocaine. We discuss the necessary investigations to rule out any serious underlying pathology. These should be considered in patients who present with chest pain after cocaine use. PMID- 26364300 TI - Matrix Gla protein regulates differentiation of endothelial cells derived from mouse embryonic stem cells. AB - Matrix Gla protein (MGP) is an antagonist of bone morphogenetic proteins and expressed in vascular endothelial cells. Lack of MGP causes vascular abnormalities in multiple organs in mice. The objective of this study is to define the role of MGP in early endothelial differentiation. We find that expression of endothelial markers is highly induced in Mgp null organs, which, in wild type, contain high MGP expression. Furthermore, Mgp null embryonic stem cells express higher levels of endothelial markers than wild-type controls and an abnormal temporal pattern of expression. We also find that the Mgp-deficient endothelial cells adopt characteristics of mesenchymal stem cells. We conclude that loss of MGP causes dysregulation of early endothelial differentiation. PMID- 26364301 TI - Scale-up of a physiologically-based pharmacokinetic model to predict the disposition of monoclonal antibodies in monkeys. AB - Preclinical assessment of monoclonal antibody (mAb) disposition during drug development often includes investigations in non-human primate models. In many cases, mAb exhibit non-linear disposition that relates to mAb-target binding [i.e., target-mediated disposition (TMD)]. The goal of this work was to develop a physiologically-based pharmacokinetic (PBPK) model to predict non-linear mAb disposition in plasma and in tissues in monkeys. Physiological parameters for monkeys were collected from several sources, and plasma data for several mAbs associated with linear pharmacokinetics were digitized from prior literature reports. The digitized data displayed great variability; therefore, parameters describing inter-antibody variability in the rates of pinocytosis and convection were estimated. For prediction of the disposition of individual antibodies, we incorporated tissue concentrations of target proteins, where concentrations were estimated based on categorical immunohistochemistry scores, and with assumed localization of target within the interstitial space of each organ. Kinetics of target-mAb binding and target turnover, in the presence or absence of mAb, were implemented. The model was then employed to predict concentration versus time data, via Monte Carlo simulation, for two mAb that have been shown to exhibit TMD (2F8 and tocilizumab). Model predictions, performed a priori with no parameter fitting, were found to provide good prediction of dose-dependencies in plasma clearance, the areas under plasma concentration versu time curves, and the time course of plasma concentration data. This PBPK model may find utility in predicting plasma and tissue concentration versus time data and, potentially, the time-course of receptor occupancy (i.e., mAb-target binding) to support the design and interpretation of preclinical pharmacokinetic-pharmacodynamic investigations in non-human primates. PMID- 26364302 TI - The molecular chaperone CCT modulates the activity of the actin filament severing and capping protein gelsolin in vitro. AB - The oligomeric molecular chaperone CCT is essential for the folding of the highly abundant protein actin, which in its native state forms actin filaments that generate the traction forces required for cell motility. In addition to folding proteins, CCT can provide a platform for protein complex assembly and binds actin filaments assembled in vitro. Some individual subunits of CCT, when monomeric, have been shown to be functionally active, and in particular, the CCTepsilon subunit is involved in the serum response factor pathway that controls actin transcription. Thus, there is a complex interplay between CCT and actin that extends beyond actin folding. CCT has recently been shown to bind gelsolin, an actin filament severing protein that increases actin dynamics by generating filament ends for further actin polymerization. However, the biological significance of the CCT:gelsolin interaction is unknown. Here, using a co immunoprecipitation assay, we show that CCT binds directly to gelsolin in its calcium-activated, actin-severing conformation. Furthermore, using actin filaments retained from fixed and permeabilized cells, we demonstrate that CCT can inhibit the actin filament severing activity of gelsolin. As our work and that of others shows gelsolin is not folded by CCT, the CCT:gelsolin interaction represents a novel mode of binding where CCT may modulate protein activity. The data presented here reveal an additional level of interplay between CCT and actin mediated via gelsolin, suggesting that CCT may influence processes depending on gelsolin activity, such as cell motility. PMID- 26364303 TI - Age-related thermal response: the cellular resilience of juveniles. AB - Understanding species' responses to environmental challenges is key to predicting future biodiversity. However, there is currently little data on how developmental stages affect responses and also whether universal gene biomarkers to environmental stress can be identified both within and between species. Using the Antarctic clam, Laternula elliptica, as a model species, we examined both the tissue-specific and age-related (juvenile versus mature adult) gene expression response to acute non-lethal warming (12 h at 3 degrees C). In general, there was a relatively muted response to this sub-lethal thermal challenge when the expression profiles of treated animals, of either age, were compared with those of 0 degrees C controls, with none of the "classical" stress response genes up regulated. The expression profiles were very variable between the tissues of all animals, irrespective of age with no single transcript emerging as a universal biomarker of thermal stress. However, when the expression profiles of treated animals of the different age groups were directly compared, a very different pattern emerged. The profiles of the younger animals showed significant up regulation of chaperone and antioxidant transcripts when compared with those of the older animals. Thus, the younger animals showed evidence of a more robust cellular response to warming. These data substantiate previous physiological analyses showing a more resilient juvenile population. PMID- 26364304 TI - RE: Breast Cancer, Heart Disease, and Whispering "Fire" in a Public Theater. PMID- 26364305 TI - Response. PMID- 26364306 TI - Built Environment Features that Promote Cycling in School-Aged Children. AB - Previous research shows that children and youth who cycle to/from school are more active and fitter than those who travel by motorized modes. However, rates of cycling are low in many countries, and a better understanding of the correlates of cycling may inform the development of future interventions. This review summarizes the current literature on the built environment correlates of cycling among school-aged children and youth. While both studies of transportation and recreational cycling were eligible, the majority of the 12 included studies focused on the trip to/from school and consistently indicated that shorter distance between home and school is associated with greater odds of cycling. However, little is known about the correlates of cycling for other purposes. Furthermore, other built environment features have not been studied enough to allow strong conclusions to be drawn. Recommendations for future studies are proposed to address the limitations of current evidence. PMID- 26364308 TI - Innovations in the Use of Interactive Technology to Support Weight Management. AB - New and emerging mobile technologies are providing unprecedented possibilities for understanding and intervening on obesity-related behaviors in real time. However, the mobile health (mHealth) field has yet to catch up with the fast paced development of technology. Current mHealth efforts in weight management still tend to focus mainly on short message systems (SMS) interventions, rather than taking advantage of real-time sensing to develop just-in-time adaptive interventions (JITAIs). This paper will give an overview of the current technology landscape for sensing and intervening on three behaviors that are central to weight management: diet, physical activity, and sleep. Then five studies that really dig into the possibilities that these new technologies afford will be showcased. We conclude with a discussion of hurdles that mHealth obesity research has yet to overcome and a future-facing discussion. PMID- 26364309 TI - Anoctamin-1 Cl(-) channels in nociception: activation by an N-aroylaminothiazole and capsaicin and inhibition by T16A[inh]-A01. AB - BACKGROUND: Anoctamin 1 (ANO1 or TMEM16A) Ca(2+)-gated Cl(-) channels of nociceptor neurons are emerging as important molecular components of peripheral pain transduction. At physiological intracellular Cl(-) concentrations ([Cl(-)]i) sensory neuronal Cl(-) channels are excitatory. The ability of sensory neuronal ANO1 to trigger action potentials and subsequent nocifensive (pain) responses were examined by direct activation with an N-aroylaminothiazole. ANO1 channels are also activated by intracellular Ca(2+) ([Ca(2+)]i) from sensory neuronal TRPV1 (transient-receptor-potential vallinoid 1) ion channels and other noxicant receptors. Thus, sensory neuronal ANO1 can facilitate TRPV1 triggering of action potentials, resulting in enhanced nociception. This was investigated by reducing ANO1 facilitation of TRPV1 effects with: (1) T16A[inh]-A01 ANO1-inhibitor reagent at physiological [Cl(-)]i and (2) by lowering sensory neuronal [Cl(-)]i to switch ANO1 to be inhibitory. RESULTS: ANO1 effects on action potential firing of mouse dorsal root ganglia (DRG) neurons in vitro and mouse nocifensive behaviors in vivo were examined with an N-aroylaminothiazole ANO1-activator (E-act), a TRPV1 activator (capsaicin) and an ANO1-inhibitor (T16A[inh]-A01). At physiological [Cl(-)]i (40 mM), E-act (10 uM) increased current sizes (in voltage-clamp) and action potential firing (in current-clamp) recorded in DRG neurons using whole cell electrophysiology. To not disrupt TRPV1 carried-Ca(2+) activation of ANO1 in DRG neurons, ANO1 modulation of capsaicin-induced action potentials was measured by perforated-patch (Amphotericin-B) current-clamp technique. Subsequently, at physiological [Cl(-)]i, capsaicin (15 uM)-induced action potential firing was diminished by co-application with T16A[inh]-A01 (20 uM). Under conditions of low [Cl(-)]i (10 mM), ANO1 actions were reversed. Specifically, E-act did not trigger action potentials; however, capsaicin-induced action potential firing was inhibited by co-application of E-act, but was unaffected by co-application of T16A[inh]-A01. Nocifensive responses of mice hind paws were dramatically induced by subcutaneous injections of E-act (5 mM) or capsaicin (50 uM). The nocifensive responses were attenuated by co-injection with T16A[inh]-A01 (1.3 mM). CONCLUSIONS: An ANO1-activator (E-act) induced [Cl(-)]i-dependent sensory neuronal action potentials and mouse nocifensive behaviors; thus, direct ANO1 activation can induce pain perception. ANO1-inhibition attenuated capsaicin triggering of action potentials and capsaicin-induced nocifensive behaviors. These results indicate ANO1 channels are involved with TRPV1 actions in sensory neurons and inhibition of ANO1 could be a novel means of inducing analgesia. PMID- 26364307 TI - Built Environments and Active Living in Rural and Remote Areas: a Review of the Literature. AB - Rural children and adults are more likely to have obesity than their urban counterparts even after adjustment for individual-level behaviors, suggesting that rural environments may promote obesity. The rural built environment may be an important area of research that can help us understand rural-urban disparities in obesity. The purpose of this review is to summarize the rural built environment and active living literature, and to address key issues, gaps, and observations in the field. A literature review was conducted in spring 2015 to identify research published from 2000 to 2015. Our review suggests that limited active living built environments in rural communities and unique rural barriers to physical activity may contribute to a higher prevalence of obesity compared to urban populations. More empirical research is needed to build the evidence-base for the association between rural built environments, active living, and obesity. School- and community-based policies that expand active living opportunities in rural areas should also be closely examined. PMID- 26364310 TI - Production of herbicide-resistant medicinal plant Salvia miltiorrhiza transformed with the bar gene. AB - In this study, we successfully performed Agrobacterium-mediated genetic transformation of Salvia miltiorrhiza and produced herbicide-resistant transformants. Leaf discs of S. miltiorrhiza were infected with Agrobacterium tumefaciens EHA105 harboring pCAMBIA 3301. The pCAMBIA 3301 includes an intron containing gus reporter and a bar selection marker. To increase stable transformation efficiency, a two-step selection was employed which consists of herbicide resistance and gus expression. Here, we put more attention to the screening step of herbicide resistance. The current study provides an efficient screening system for the transformed plant of S. miltiorrhiza harboring bar gene. To determine the most suitable phosphinothricin concentration for plant selection, non-transformed leaf discs were grown on selection media containing six different phosphinothricin concentrations (0, 0.2, 0.4, 0.6, 0.8, and 1.0 mg/l). Based on the above results of non-transformed calluses, the sensitivity of phosphinothricin (0, 0.4, 0.8, 1.2, 1.6 mg/l) was tested in the screening of transgenic S. miltiorrhiza. We identified that 0.6 mg/l phosphinothricin should be suitable for selecting putatively transformed callus because non-transformed callus growth was effectively inhibited under this concentrations. When sprayed with Basta, the transgenic S. miltiorrhiza plants were tolerant to the herbicide. Hence, we report successful transformation of the bar gene conferring herbicide resistance to S. miltiorrhiza. PMID- 26364311 TI - Effect of salinity on methanogenic propionate degradation by acclimated marine sediment-derived culture. AB - Degradation of propionate under high salinity is needed for biomethane production from salt-containing feedstocks. In this study, marine sediment-derived culture was evaluated to determine the effect of salinity on methanogenic propionate degradation. Microbes in marine sediments were subjected to fed-batch cultivation on propionate for developing acclimatized cultures. The rate of propionate degradation increased eightfold during 10 rounds of cultivation. Microbial community composition was determined through pyrosequencing of 16S rRNA gene amplicons after 10 rounds of cultivation. Taxa analysis was conducted for the reads obtained by pyrosequencing. Known propionate degraders were undetectable in the acclimated culture. Comparison of bacterial taxa in the original sediment with those in the acclimated culture revealed that the populations of four bacterial taxa were significantly increased during acclimation. Methanolobus was the predominant archaea genus in the acclimated culture. The propionate degradation rate of the acclimated culture was not affected by salinity of up to equivalent of 1.9 % NaCl. The rate decreased at higher salinity levels and was more than 50 % of the maximum rate even at equivalent of 4.3 % NaCl. PMID- 26364313 TI - Linking Biomarker and Comparative Omics to Pathogens in Legumes. AB - It is envisioned that a more precise study of the association between the traits and biomarkers will dramatically decrease the time and costs required to bring new improved disease resistance lines to market. The field of omics has an enormous potential to assess diseases more precise, including the identification and understanding of pathogenic mechanisms in legume crops, and have been exemplified by a relatively large number of studies. Recently, molecular genetic studies have accumulated a huge amount of genotypic data, through a more affordable next generation sequencing (NGS) technology, causing the omics approaches to fall behind. In this paper I provide an overview of genomics and proteomics and their use in legume crops, including the use of comparative genomics to identify homologous markers within legume crops. PMID- 26364314 TI - Two heads are better than one: Australian tobacco control experts' and mental health change champions' consensus on addressing the problem of high smoking rates among people with mental illness. AB - Objective The aims of the present study were to explore the beliefs of Australian experts in tobacco control and change champions working in mental health and tobacco cessation, and to identify measures for addressing the problem of high smoking rates for people with mental illness. Methods Qualitative interviews were undertaken to explore participants' views, and the Delphi technique was used to achieve consensus on ways in which the problem would be best addressed. Results This consensus centred on the need for leadership within the mental health system. The problem was reconceptualised from being solely the responsibility of the mental health sector into an issue that requires the combined resources of a partnership and shared leadership between government and non-government services, public health leaders, policy makers and people with mental illness and their families. Conclusions Collaboration would raise the priority of the issue, reduce the debilitating effect of stigma and discrimination within the mental health sector and would place smoking reduction firmly on the political and public agenda. A recovery-orientated focus would increase the skill base and be inclusive of workers, families and carers of people with mental illness who face smoking issues on a daily basis. Reconceptualising this as an issue that would benefit from cooperation and partnerships would disrupt the notion that the problem is solely the responsibility of the mental health sector. What is known about the topic? Rates of smoking have remained high for people with mental illness despite population-wide public health strategies successfully reducing smoking rates in the general population. For people with mental illness, the benefits of quitting smoking for both their mental and physical health are overshadowed by concerns about the complexity of their needs. There is a lack of knowledge about how smoking cessation support can be improved to increase success rates in smokers with mental illness. What does this paper add? The present study is the first to bring a cross-sector lens of public health and mental health 'experts' together to discuss the reasons for the high rates of smoking among people with mental illness and to obtain their shared agreement on solutions. This Australian-specific study analyses participants' responses to the problem representation and reveals what the issue is considered to be, where action should occur and how the problem should be resolved. What are the implications for practitioners? For the Australian context, there is a need for leadership and a consistent smoke-free message about the benefits of not smoking. Staff working in mental health require training in providing brief interventions, motivational interviewing and pharmacological support. Joining together as a partnership of government and non-government services, including public health leaders and policy makers, and involving people with mental illness and their families, would benefit all concerned. PMID- 26364315 TI - Heterologous complementation studies in Escherichia coli with the Hyp accessory protein machinery from Chloroflexi provide insight into [NiFe]-hydrogenase large subunit recognition by the HypC protein family. AB - Six Hyp maturation proteins (HypABCDEF) are conserved in micro-organisms that synthesize [NiFe]-hydrogenases (Hyd). Of these, the HypC chaperones interact directly with the apo-form of the catalytically active large subunit of Hyd enzymes and are believed to transfer the Fe(CN)2CO moiety of the bimetallic cofactor from the Hyp machinery to this large subunit. In E. coli, HypC is specifically required for maturation of Hyd-3 while its paralogue, HybG, is specifically required for Hyd-2 maturation; either HypC or HybG can mature Hyd-1. In this study, we demonstrate that the products of the hypABFCDE operon from the deeply branching hydrogen-dependent and obligate organohalide-respiring bacterium Dehalococcoides mccartyi strain CBDB1 were capable of maturing and assembling active Hyd-1, Hyd-2 and Hyd-3 in an E. coli hyp mutant. Maturation of Hyd-1 was less efficient, presumably because HypB of E. coli was necessary to restore optimal enzyme activity. In a reciprocal maturation study, the highly O2 sensitive H2-uptake HupLS [NiFe]-hydrogenase from D. mccartyi CBDB1 was also synthesized in an active form in E. coli. Together, these findings indicated that HypC from D. mccartyi CBDB1 exhibits promiscuity in its large subunit interaction in E. coli. Based on these findings, we generated amino acid variants of E. coli HybG capable of partial recovery of Hyd-3-dependent H2 production in a hypC hybG double null mutant. Together, these findings identify amino acid regions in HypC accessory proteins that specify interaction with the large subunits of hydrogenase and demonstrate functional compatibility of Hyp accessory protein machineries. PMID- 26364316 TI - The European Network for Translational Research in Atrial Fibrillation (EUTRAF): objectives and initial results. AB - Atrial fibrillation (AF) is the most common sustained arrhythmia in the general population. As an age-related arrhythmia AF is becoming a huge socio-economic burden for European healthcare systems. Despite significant progress in our understanding of the pathophysiology of AF, therapeutic strategies for AF have not changed substantially and the major challenges in the management of AF are still unmet. This lack of progress may be related to the multifactorial pathogenesis of atrial remodelling and AF that hampers the identification of causative pathophysiological alterations in individual patients. Also, again new mechanisms have been identified and the relative contribution of these mechanisms still has to be established. In November 2010, the European Union launched the large collaborative project EUTRAF (European Network of Translational Research in Atrial Fibrillation) to address these challenges. The main aims of EUTRAF are to study the main mechanisms of initiation and perpetuation of AF, to identify the molecular alterations underlying atrial remodelling, to develop markers allowing to monitor this processes, and suggest strategies to treat AF based on insights in newly defined disease mechanisms. This article reports on the objectives, the structure, and initial results of this network. PMID- 26364317 TI - Solid-Phase Extraction of Sulfur Mustard Metabolites Using an Activated Carbon Fiber Sorbent. AB - A novel solid-phase extraction method using activated carbon fiber (ACF) was developed and validated. ACF has a vast network of pores of varying sizes and microporous structures that result in rapid adsorption and selective extraction of sulfur mustard metabolites according to the pH of eluting solvents. ACF could not only selectively extract thiodiglycol and 1-methylsulfinyl-2-[2-(methylthio) ethylsulfonyl]ethane eluting a 9:1 ratio of dichloromethane to acetone, and 1,1' sulfonylbis[2-(methylsulfinyl)ethane] and 1,1'-sulfonylbis- [2-S-(N acetylcysteinyl)ethane] eluting 3% hydrogen chloride in methanol, but could also eliminate most interference without loss of analytes during the loading and washing steps. A sample preparation method has been optimized for the extraction of sulfur mustard metabolites from human urine using an ACF sorbent. The newly developed extraction method was applied to the trace analysis of metabolites of sulfur mustard in human urine matrices in a confidence-building exercise for the analysis of biomedical samples provided by the Organisation for the Prohibition of Chemical Weapons. PMID- 26364318 TI - A multi-perspective service evaluation exploring tuberculosis contact screening attendance among adults at a North London hospital. AB - BACKGROUND: Non-attendance at TB contact screening clinics has been highlighted as a common phenomenon across a number of sites during recruitment to the PREDICT TB Study. This has obvious implications for the safety of patients, their communities and for NHS resources. The objective of this study was to explore why adults who have been in contact with TB do, and do not, attend their screening appointment, thereby allowing identification of interventions to reduce non attendance. METHODS: A multi-method approach was taken using 15 questionnaires with adults who attended for screening, 15 telephone questionnaires with adults who did not attend and in-depth interviews with 8 TB nurses. Interviews were coded to trace emerging descriptive themes, then refined through an iterative process of interpretation and recoding. RESULTS: Findings from the questionnaires and interviews were categorized into three principle themes following analysis: awareness, hospital factors and leadership. These themes deconstruct the complex phenomena of patients' lack of attendance at this TB contact screening service. CONCLUSION: Recommendations related to issues of leadership, outreach services, flexibility of clinic timing and awareness amongst both the local community and GPs were made. PMID- 26364319 TI - School outbreak of Escherichia coli O157 with high levels of transmission, Staffordshire, England, February 2012. AB - BACKGROUND: Verocytotoxin-producing Escherichia coli (VTEC) are bacteria that cause infectious gastroenteritis and in certain settings can cause widespread infection due to secondary transmission. We describe the findings of an investigation of a school-based outbreak of VTEC in Staffordshire, England. METHODS: Outbreak investigation at a school in February 2012 after two children were diagnosed with VTEC infection. Cases were defined as pupils and staff (or their household contacts) with gastrointestinal symptoms or asymptomatic screened persons, with laboratory confirmed VTEC O157 infection (phage type 32, verocytotoxin 2) occurring on or after 1 February 2012. Microbiological tests of food and faecal samples plus screening of asymptomatic contacts were undertaken. Epidemiological and clinical data were descriptively analysed. RESULTS: Thirty eight cases were detected. Nineteen were asymptomatic and identified via screening of 191 pupils. Infection was introduced into the school from an earlier household cluster, followed by extensive person-to-person transmission within the nursery/infant group with limited spread to the wider school population. CONCLUSIONS: Control measures included several interventions, in particular, universal screening of pupils and staff. Screening during school outbreaks is not underpinned by guidance but proved to be a key control measure. Screening of asymptomatic contacts should be considered in similar outbreaks. PMID- 26364320 TI - The impact of economic downturns and budget cuts on homelessness claim rates across 323 local authorities in England, 2004-12. AB - BACKGROUND: It is unclear why rates of homelessness claims in England have risen since 2010. We used variations in rates across local authorities to test the impact of economic downturns and budget cuts. METHODS: Using cross-area fixed effects models of data from 323 UK local authorities between 2004 and 2012, we evaluated associations of changes in statutory homelessness rates with economic activity (Gross Value Added per capita), unemployment, and local and central government expenditure. RESULTS: Each 10% fall in economic activity was associated with an increase of 0.45 homelessness claims per 1000 households (95% CI: 0.10-0.80). Increasing rates of homelessness were also strongly linked with government reductions in welfare spending. Disaggregating types of welfare expenditure, we found that strongest associations with reduced homelessness claims were spending on social care, housing services, discretionary housing payments and income support for older persons. CONCLUSIONS: Recession and austerity measures are associated with significant increases in rates of homelessness assistance. These findings likely understate the full burden of homelessness as they only capture those who seek aid. Future research is needed to investigate what is happening to vulnerable groups who may not obtain assistance, including those with mental health problems and rough sleepers. PMID- 26364322 TI - Response: Re: Performance on the Maintenance of Certification for Family Physicians (MC-FP) Examination: Comparison of Initial Certifiers with Experienced Physicians. PMID- 26364321 TI - Physiologic MRI for assessment of response to therapy and prognosis in glioblastoma. AB - Aside from bidimensional measurements from conventional contrast-enhanced MRI, there are no validated or FDA-qualified imaging biomarkers for high-grade gliomas. However, advanced functional MRI techniques, including perfusion- and diffusion-weighted MRI, have demonstrated much potential for determining prognosis, predicting therapeutic response, and assessing early treatment response. They may also prove useful for differentiating pseudoprogression from true progression after temozolomide chemoradiation and pseudoresponse from true response after anti-angiogenic therapy. This review will highlight recent developments using these techniques and emphasize the need for technical standardization and validation in prospective studies in order for these methods to become incorporated into standard-of-care imaging for brain tumor patients. PMID- 26364324 TI - 2014: Rural Medicare Advantage Enrollment Update. AB - Key Data Findings. (1) Reclassification of rural and urban county designations (due to the switch from 2000 census data to 2010 census data) resulted in a 10 percent decline in the number of Medicare eligible Americans living in rural counties in 2014 (from roughly 10.7 million to 9.6 million). These changes also resulted in a decline in the number of MA enrollees considered to be living in a rural area, from 2.19 million to 1.95 million. However, the percentage of Medicare beneficiaries enrolled in MA and prepaid plans in rural areas declined only slightly from 20.6 percent to 20.3 percent. (2) Rural Medicare Advantage (MA) and other prepaid plan enrollment in March 2014 was nearly 1.95 million, or 20.3 percent of all rural Medicare beneficiaries, an increase of more than 216,000 from March 2013. Enrollment increased to 1.99 million (20.4 percent) in October 2014. (3) In March 2014, 56 percent of rural MA enrollees were enrolled in Preferred Provider Organization (PPO) plans, 29 percent were enrolled in Health Maintenance Organization (HMO) or Point-of-Service (POS) plans, 7 percent were enrolled in Private Fee-for-Service (PFFS) plans, and 8 percent were enrolled in other prepaid plans, including Cost plans and Program of All Inclusive Care for the Elderly (PACE) plans. (4) States with the highest percentage of rural Medicare beneficiaries enrolled in MA and other prepaid plans include Minnesota (49.1 percent), Hawaii (41.1 percent), Pennsylvania (35.4 percent), Wisconsin (34.3 percent), New York (30.4 percent), and Ohio (30.1 percent). PMID- 26364323 TI - The American Board of Family Medicine Foundation Inaugurates the G. Gayle Stephens Keystone Conference Series. PMID- 26364325 TI - Schedules of Controlled Substances: Removal of [123I]Ioflupane From Schedule II of the Controlled Substances Act. Final rule. AB - With the issuance of this final rule, the Administrator of the Drug Enforcement Administration removes [123I]ioflupane from the schedules of the Controlled Substances Act. This action is pursuant to the Controlled Substances Act which requires that such actions be made on the record after an opportunity for a hearing through formal rulemaking. Prior to the effective date of this rule, [123I]ioflupane was, by definition, a schedule II controlled substance because it is derived from cocaine via ecgonine, both of which are schedule II controlled substances. This action removes the regulatory controls and administrative, civil, and criminal sanctions applicable to controlled substances, including those specific to schedule II controlled substances, on persons who handle (manufacture, distribute, reverse distribute, dispense, conduct research, import, export, or conduct chemical analysis) or propose to handle [123I]ioflupane. PMID- 26364326 TI - Developmental Strategies and Challenges of Rural Accountable Care Organizations. AB - This policy brief shares insights gained from site visits in 2013 to four Accountable Care Organizations (ACOs) serving rural Medicare beneficiaries. Initial strategic decisions made and challenges faced as the ACOs were being developed can inform development of other rural ACOs. Key Findings. (1) The rural ACOs we studied were formed as a step toward a value-driven rural delivery system, recognizing that ACO participation may or may not have a short term return on investment. (2) Common rural ACO strategies to increase health care value include care management, post-acute care redesign, medication management, and end-of-life care planning. (3) Access to data is an important enabler of population health management, care management, and provider participation. PMID- 26364327 TI - A Rural Taxonomy of Population and Health-Resource Characteristics. AB - This policy brief reports the newly developed taxonomy of rural places based on relevant population and health-resource characteristics; and discusses how this classification tool can be utilized by policy makers and rural communities. Key Findings. (1) We classified 10 distinct types of rural places based on characteristics related to both demand (population) and supply (health resources) sides of the health services market. (2) In descending order, the most significant dimensions in our classification were facility resources, provider resources, economic resources, and age distribution. (3) Each type of rural place was distinct from other types of places based on one or two defining dimensions. PMID- 26364328 TI - Immunization and Vaccine-related Implementation Research Advisory Committee (IVIR AC): summary of conclusions and recommendations, 9-11 June 2015 meeting. THEME: Research to minimize barriers and improve coverage of vaccines currently in use. PMID- 26364329 TI - Performance of acute flaccid paralysis (AFP)surveillance and incidence of poliomyelitis (data received in WHO Headquarters as of 25 August 2015). PMID- 26364330 TI - Review calls for community nursing 'field'. PMID- 26364331 TI - SPECIAL REPORT: CASELOADS. PART 1: SNAPSHOT. PMID- 26364332 TI - Understanding postpartum psychosis. PMID- 26364333 TI - The rough with the smooth: managing nappy rash. PMID- 26364334 TI - Listening to parents to improve health visiting practice. AB - Listening to the "voice" of the service user is now widely accepted as central to the delivery of high quality healthcare. This paper presents an overview of the importance of service user engagement and personalised care in health visiting with a brief review of recent policy and research. A personalised approach to health visiting practice is recommended to improve service user experience and uptake of the health visiting service offer and this is considered most significant when engaging "hard to reach" groups. A project report on a service user experience strategy within the 0-19 service of a NHS Trust in England is presented which describes initiatives to develop a health visiting and school nursing service that listens to service users. A cyclical service user engagement model which incorporates continuous reviews and service reconfiguration is described with examples of service changes in response to expressed local needs. PMID- 26364335 TI - The 'Born Bonded' programme: an antenatal service evaluation. AB - A service evaluation of an antenatal programme to improve 'bonding' with the unborn child is described. This was an attempt to see if Comfort Zone which was previously found to be useful by parents could also be helpful as part of an antenatal programme. As this was a preliminary investigation pragmatism was prioritised over a robust design. However given the limitations in the measures used all participants reported either the same or an improved bond with their unborn child. Further research is required to gather evidence for the effectiveness of Comfort Zone and its usefulness antenatally. PMID- 26364336 TI - The integrated model of restorative supervision for use within safeguarding. AB - This paper offers a review of a new model of supervision; the integrated restorative model, to underpin effective safeguarding supervision in health settings. This seeks to capitalize on the benefits of using both restorative supervision (Wallbank, 2010) and an integrated model commonly referred to as the 4x4x4 model (Morrison 2005, Wonnacott, 2012). It challenges the notion that restorative supervision is a stand- alone supervisory process sitting outside of safeguarding supervision and demonstrates how effective safeguarding supervision needs to combine critical reflective practice and critical thinking with a restorative experience in order for the professional to feel supported and maintain their capacity to think. The paper urges health settings to ensure that individuals undertaking safeguarding supervision are appropriately trained to identify how those sessions can support professionals to retain their reflective capacity and decision-making skills. PMID- 26364337 TI - Last word with ... ELIZABETH ANIONWU CBE. PMID- 26364338 TI - Information Governance's NEXT PHASE. MOVING HIM FROM THE 'WHY' OF IG TO THE 'HOW'. PMID- 26364339 TI - GETTING STARTED WITH INFORMATION GOVERNANCE. WHAT ARE YOU WAITING FOR? PMID- 26364341 TI - The 'Keys' to Help Solve Patient Data Matching. PMID- 26364340 TI - OWNING the EHR and INFORMATION GOVERNANCE at Your Facility. PMID- 26364342 TI - IG ROUNDTABLE--Assessing Organizational Progress in Implementing IG Practices. PMID- 26364343 TI - Guiding THE DEVELOPMENT OF HEALTH INFORMATION TECHNOLOGY STANDARDS FOR HIM PRACTICES. PMID- 26364344 TI - IG from the Ground UP. PMID- 26364345 TI - Interview With Mario J. Garner, EdD, FACHE, President and CEO of New Orleans East Hospital. PMID- 26364346 TI - Finding the Path to Innovation. PMID- 26364347 TI - Trending in 2015: Population Health. PMID- 26364348 TI - Nurse Against Nurse: Horizontal Bullying in the Nursing Profession. AB - Healthcare professionals are not immune to bullying; in fact, they experience bullying at an alarming rate. Sometimes the bullying is passed down from superiors, but frequently bullying occurs between coworkers. This is known as "horizontal bullying," and it has become a serious issue within the nursing profession. Horizontal bullying between nurses can cause negative consequences for everyone involved, in particular the nurses, patients, and the entire organization. To fully address and resolve horizontal bullying in the nursing profession, we must consider many factors. The first step is to establish what constitutes bullying and to develop a clear process for dealing with it when it occurs. Before it is possible to eliminate the problem, we need to understand why bullying takes place. To be effective, solutions to the problem of horizontal bullying in the nursing profession must include the entire healthcare industry. PMID- 26364349 TI - A Community Hospital-County Health Department Partnership to Reduce Preventable Readmissions: Lessons Learned for Population Health Management. AB - Healthcare reform has prompted hospital executives to adopt new strategies aimed at population health management. Research regarding the broad determinants of health suggests that if hospitals are to build successful population health management models, they must engage in collaborative partnerships with a variety of community stakeholders. In this report, the author describes a collaborative partnership between a community hospital and a county health department to reduce preventable readmissions. This program illustrates the important role that health information technology (HIT), managerial systems, new processes, and hospital culture play in collaborations with external parties. On a larger scale, these facilitators are key factors in developing population health business models such as accountable care organizations. A sound hospital infrastructure should be supported by hospital leaders and staff who are held accountable for community initiatives and communicate transparently with external partners. PMID- 26364350 TI - Pay for Performance: Are Hospitals Becoming More Efficient in Improving Their Patient Experience? AB - The Centers for Medicare & Medicaid Services (CMS) changed the way hospitals interact with patients when it implemented a pay-for-performance (P4P) system. Under this system, a financial reward or penalty is based in part on measures of patient experience. The program seeks to reward healthcare providers who expand their focus from solely delivering a highly technical set of services that improves the patient's health to creating an atmosphere that makes hospitalization more humane and respectful of patients' values and preferences. Refocusing priorities requires capital investment in more "patient-friendly" facilities or funding staff training programs. This study seeks to determine whether a relationship exists between inpatient costs and the score for "overall rating of hospital" (ORH) on the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) hospital version survey. Second, if a relationship exists, the study examines how that relationship changed during the time of CMS' implementation of its P4P program. The study's findings suggest that higher-cost hospitals have higher levels of positive patient experiences, after controlling for other variables. Importantly, the research findings indicate that hospitals are becoming more efficient in delivering care associated with higher levels of patient experience, coinciding with implementation of the P4P program. PMID- 26364351 TI - Practitioner application. PMID- 26364352 TI - Facilitating Implementation of Interprofessional Collaborative Practices Into Primary Care: A Trilogy of Driving Forces. AB - Implementing interprofessional collaborative practices in primary care is challenging, and research about its facilitating factors remains scarce. The goal of this participatory action research study was to better understand the driving forces during the early stage of the implementation process of a community-driven and patient-focused program in primary care titled "TRANSforming InTerprofessional cardiovascular disease prevention in primary care" (TRANSIT). Eight primary care clinics in Quebec, Canada, agreed to participate by creating and implementing an interprofessional facilitation team (IFT). Sixty-three participants volunteered to be part of an IFT, and 759 patients agreed to participate. We randomized six clinics into a supported facilitation ("supported") group, with an external facilitator (EF) and financial incentives for participants. We assigned two clinics to an unsupported facilitation ("unsupported") group, with no EF or financial incentives. After 3 months, we held one interview for the two EFs. After 6 months, we held eight focus groups with IFT members and another interview with each EF. The analyses revealed three key forces: (1) opportunity for dialogue through the IFT, (2) active role of the EF, and (3) change implementation budgets. Decision-makers designing implementation plans for interprofessional programs should ensure that these driving forces are activated. Further research should examine how these forces affect interprofessional practices and patient outcomes. PMID- 26364353 TI - Practitioner application. PMID- 26364354 TI - Effect of Environmental Factors on Cyanobacterial Abundance and Cyanotoxins Production in Natural and Drinking Water, Bangladesh. AB - Cyanobacterial blooms commonly appear during the summer months in ponds, lakes and reservoirs in Bangladesh. In these areas, fish mortality, odorous water and fish and human skin irritation and eye inflammation have been reported. The influence of physicochemical factors on the occurrence of cyanobacteria and its toxin levels were evaluated in natural and drinking water in Bangladesh. A highly sensitive immunosorbent assay was used to detect microcystins (MCs). Cyanobacteria were found in 22 of 23 samples and the dominant species were Microcystis aeruginosa, followed by Microcystisflosaquae, Anabeana crassa and Aphanizomenon flosaquae. Cyanobacterial abundance varied from 39 to 1315 x 10(3) cells mL(-1) in natural water and 31 to 49 x 10(3) cells mL(-1) in tap water. MC concentrations were 25-82300 pg mL(-1) with the highest value measured in the fish research pond, followed by Ishakha Lake. In tap water, MC concentrations ranged from 30-32 pg mL(-1). The correlation between nitrate-nitrogen (NO3-N) concentration and cyanobacterial cell abundance was R2 = 0.62 while that between cyanobacterial abundance and MC concentration was R2 = 0.98. The increased NO3-N from fish feed, organic manure, poultry and dairy farm waste and fertilizer from agricultural land eutrophicated the water bodies and triggered cyanobacterial bloom formation. The increased amount of cyanobacteria produced MCs, subsequently reducing the water quality. PMID- 26364355 TI - Application of Probiotic, Prebiotic and Synbiotic for the Control of Streptococcosis in Tilapia Oreochromis niloticus. AB - One of the fish diseases that is becoming the main problem in tilapia culture is streptococcosis caused by Streptococcus agalactiae. Application of probiotic, prebiotic and synbiotic are expected to be an alternative for controlling the disease. The purpose of this study was to examine the effectiveness of the administration of probiotic, prebiotic and synbiotic through artificial feed to control streptococcosis in tilapia. This study consisted of five treatments with three replications, namely positive control, negative control; 1% probiotic treatment; 2% prebiotic treatment and synbiotic treatment (1% probiotic and 2% prebiotic). Results showed that fish survival rate before the challenge test for all treatments was between 95 and 100%. Growth and feed conversion ratios in probiotic, prebiotic and synbiotic treatments were better than that of the controls. After the challenge test, the fish survival rate in probiotic, prebiotic and synbiotic treatments were 74.08, 74.08 and 85.19%, respectively; whereas, in the positive control it was only 18.52%. Results showed that S. agalactiae bacteria could be found in the brain, kidney, liver and eyes. The number of S. agalactiae bacteria and the damage level of various target organs in probiotic, prebiotic and synbiotic treatments were lower than that of positive control. PMID- 26364357 TI - Clarification of Tomato Juice with Polygalacturonase Obtained from Tomato Fruits Infected by Aspergillus niger. AB - Two varieties of tomato fruits commonly available in Nigerian markets are the Roma VF and Ibadan local varieties of tomato fruits. The Roma VF fruits are oval in shape. It is a common type of cultivar in the Northern region of Nigeria and it is not susceptible to cracking. The Ibadan local variety of tomato fruits is a local variety commonly found on farmers fields in South-western region of Nigeria. They are highly susceptible to cracking. The Ibadan local variety was employed for this research. There are lots of benefits derived from the consumption of tomato fruits. The fruits can be made into tomato juice clarified with pectinases. Polygalacturonase is one of the pectinases used commercially in the clarification of fruit juice from different fruits. This study examined the production of polygalacturonase during the deterioration of tomato fruits by Aspergillus niger and the role of the purified polygalacturonase in the clarification of tomato juice. Tomato fruits of the Ibadan local variety were inoculated with mycelia discs containing spores of a 96-h-old culture of Aspergillus niger served as the inoculum. The organism from the stock culture was subcultured onto potato dextrose agar plates. The extraction of polygalacturonase after 10 days of incubation at 27 degrees C was carried out by homogenizing the fruits with liquid extractant using the MSE homogenizer after the deteriorated fruits had been chilled for 30 min inside a freezer. Control fruits were similarly treated except that sterile potato dextrose agar served as the inoculum. The effect of different temperature of incubation and different volume of enzyme on the tomato juice from the tomato fruits was investigated. Extracts from the inoculated fruits exhibited appreciable polygalacturonase activity. The juice with polygalacturonase was visually clearer and more voluminous than the juice treated with water for all parameters studied. The highest volume of juice was obtained after an incubation period of 30 min for the tomato fruits. The increase in juice yield can be attributed to the hydrolysis of pectin which releases the sap inside the cells of the pulp. The occurrence of polygalacturonase in tomato tissues infected by A. niger coupled with the trace amount in the non-infected tissues suggests that the enzyme is of fungal origin. The role of the polygalacturonase in the clarification process was established. This study will be very useful for industrial tomato juice production. PMID- 26364356 TI - Prevention of Bacterial Biofilms Formation on Urinary Catheter by Selected Plant Extracts. AB - In this study, we investigated the feasibility of using Psidium guajava, Mangifera indica and Ocimum gratissimum leaf extracts in preventing Escherichia coli biofilm formation. The plants extractions were done with methanol under cold extraction. The various concentrations 5.0, 10.0 and 20.0 mg mL(-1) were used to coat 63 catheters under mild heat from water bath. Biofilm formation on the catheter was induced using cultures of E. coli. Biofilm formation was evaluated using aerobic plate count and turbidity at 600 nm. From the obtained results, Psidium guajava, Mangifera indica and Ocimum gratissimum delayed the onset of biofilm formation for a week. Ocimum gratissimum coated catheter had the highest inhibitory effect at 5.0, 10.0 and 20.0 mg mL(-1) with bacterial count ranging from 2.2 x 10(5)-7.0 x 10(4) and 5.7 x 10(5)-3.7 x10(5) for 120 and 128 h, respectively. The Psidium guajava coated catheter had the lowest inhibitory effect at 5.0, 10.0 and 20.0 mg mL(-1), with bacterial count ranging between 4.3 x 10(5)-1.9 x 10(3) and 7.7 x 10(5)-3.8 x 10(5) for 120 and 128 h, respectively. Despite the antimicrobial activities, the differences in the activity of these plant extracts were statistically not significant (p < 0.05). PMID- 26364358 TI - Application of Molecular and Serological Methods for Rapid Detection of Mycoplasma gallisepticum Infection (Avian mycoplasmosis). AB - Mycoplasma infection is a major problem in veterinary medicine and in poultry production. The pathogen has many strains, so that diagnosis of the disease using culture method is not effective. The objective of this work was to evaluate the prevalence of Mycoplasma gallisepticum (MG) in Kuwait poultry farms using serology and molecular methods in comparison to the culture under specific conditions. A total of 50 swab samples from choanal cleft and tracheal samples and blood samples were obtained from three different local farms, the blood samples were processed for an Enzyme Linked Immunosorbent Assay (ELISA) detection and the swab samples for Polymerase Chain Reaction (PCR) and culture methods detection. A PCR diagnostic kit (VenoMGs) and ELISA diagnostic kit (ProFLOK), were used in comparison to the traditional culture method, to study the spread of this disease in samples from broiler and layer flocks. Fifty chicken samples were tested for mycoplasmosis, samples tested with ELISA gave 24 positive (48%) and 29 were positive by PCR (58%) and only seven (14%) were positive with culture methods. Swab samples obtained from the choanal cleft gave more positive (60%) with PCR than tracheal samples (56.6%). The culture gave 20 and 5% positive, respectively for tracheal and choanal samples. The methods reported here are of high sensitivity and specificity for Mycoplasma. Both the PCR and ELISA methods are superior to culture method for detection of avian mycoplasmosis. This study showed that MG infection is prevalent in commercial broiler and layer chickens in Kuwait poultry farms. The use of these methods for surveillance of the disease will establish data concerning the predominant Mycoplasmosis diseases in Kuwait if done on a large scale. PMID- 26364359 TI - Quality of Dried Bacillus NP5 and its Effect on Growth Performance of Tilapia (Oreochromis niloticus). AB - The main things that need to be considered in the preparation of probiotics are viability during preparation and storage which are the disadvantages of the use of fresh culture probiotics. Dried probiotic can be applied through the feed, easy to be applied and has a long shelf life but application of dried probiotic in aquaculture is still not widely studied. This study aimed to evaluate the quality of dried Bacillus NP5 as the probiotic through in vitro assays and determine the best dose for the growth performance of tilapia. The treatment of in vitro assays including the production of dried probiotic without using of the coating material and dried by spray drying method (NS); freeze drying method (NF); with using of the coating material and dried by spray drying method (WS); freeze drying method (WF). The treatment which showed the best result at in vitro assays was applied for in vivo assays. The in vivo assays containing 4 treatments and 5 replicates which were control (K) and the administration of dried Bacillus NP5 Rf(R) (10(10) CFU g(-1)) in feed with dose of 0.5% (A), 1% (B) and 2% (C). The fish fed 3 times a day by at satiation for 28 days. Probiotic that encapsulated by maltodextrin and dried by spray drying method that stored in room temperature had the higher percentage product, viability after drying process and storage. The administration of 0.5% dried Bacillus NP5 showed the best growth performance in tilapia. PMID- 26364360 TI - Toxicity and Traces of Hg, Pb and Cd in the Hepatopancreas, Gills and Muscles of Perna viridis from Jakarta Bay, Indonesia. AB - Heavy metals contamination on the coast of Jakarta Bay has led to the level of pollution and can cause toxicity to organisms living in the sea, i.e., green mussels. Green mussels have the ability to detoxify metals entering their bodies. Their ability to accumulate metals is higher than other aquatic animals. This is due to their sedentary life which prevents them from avoiding the effects of pollution and their high tolerance to certain metals. The high concentration of metal content would be toxic to the cell because metal ions can act as oxidants and bind to organic and protein molecules. The results of the study showed that traces of heavy metals were detected in the hepatopancreas, gills, muscles and gonads organs of the mussels living in the waters of Muara Angke. Lead (Pb) and cadmium (Cd) were found in all four organs, while mercury (Hg) was not detected in the muscles. Traces of Hg and Cd were not detected in hepatopancreas, gills, muscles and gonads of green mussels in Panimbang, while Pb was detected by 0.00 1 in the male gonads and 0.01 in hepatopancreas. The concentration of Pb in the male gonads are still below the acceptable limit and concentration of Pb in the hepatopancreas is relatively equivalent to the acceptable limit. Metal detection in the organs above shows that the Muara Angke waters tend to be polluted and have an impact on the mussels weight loss as a result of heavy metal toxicity. PMID- 26364361 TI - [Top secret]. PMID- 26364362 TI - [PCSK9 inhibitors. A new approach for treatment of hypercholesterolemia]. AB - To date HMG-CoA-reductase inhibitors are the most effective drugs for reduction of LDL-cholesterol levels and for prevention of cardiovascular events. Inhibition of the enzyme PCSK9 (proprotein convertase subtilisin/kexin type 9), which is involved in depletion of the LDL-receptor, is a new pharmacologic approach. Inhibition of PCSK9 by monoclonal antibodies provokes an additional reduction of LDL-cholesterol levels by 50-60 % in addition to statins. Previous phase III studies indicate good compatibility. Ongoing long-term studies will answer questions of safety and influence on cardiovascular events. Although those results are not available yet, alirocumab and evolocumab have already been recommendd for approval. PMID- 26364363 TI - [Age-related macular degeneration - biology and treatment]. AB - Age-related macular degeneration (AMD) is the main cause for legal blindness of the elderly in the industrialized world and due to the demographic changes of the Western societies the prevalence is expected to increase strongly. The late forms of this disease are differentiated into geographic atrophy and exsudative (wet) AMD, where vessels grow from the choroid into the retina. On a biological level, the most important structure ofAMD pathogenesis in the photoreceptor/retinal pigment epithelium (RPE)/choroid complex. The interaction of the components of this structure enables the photoreceptors to function. Age-related alterations of this complex play an important role in the development of AMD. The exact triggers for AMD onset, however, are not known. There are no available therapies for the early forms of AMD or for geographic atrophy. However, the exsudative form can be treated by inhibiting vascular endothelial growth factor (VEGF). The currently available therapeutics (ranibizumab, aflibercept, bevacizumab) show good results in the clinic, however, in order to uphold the therapeutic effect they have to be regularly injected into the vitreous body. The inhibitors differ on a molecular level as well as on a biological level concerning their interaction with retinal pigment epithelial cells. PMID- 26364364 TI - [Influence of lifestyle on the risk of myocardial infarction. Four out of five events avoidable]. PMID- 26364365 TI - [Psoriasis and rosacea - more than just skin diseases. News from the 48th congress of the German Dermatological Society in Berlin]. PMID- 26364366 TI - [Current perspectives on evidence based medicine]. AB - Modern medicine and pharmacy practice has to be based on evidence. However, during the last years some problems have evolved concerning the proper use of the established methods. Some perspectives have been discussed at the annual congress of the German Network for Evidence-based Medicine. PMID- 26364369 TI - [E-health--a no-brainer?]. PMID- 26364368 TI - [Antacids may be frequently discontinued]. PMID- 26364370 TI - [Hygiene measures in MRSA infections. KRINKO directive versus scientific evidence]. PMID- 26364371 TI - [MRSA decolonization strategies and treatment of MRSA sepsis. News from Bad Honnef Symposium of the Paul Ehrlich Society for Chemotherapy]. PMID- 26364372 TI - [Clostridium difficile infection - an update]. AB - Clostridium difficile infection represents a severe illness which very often results in emergency surgery, intensive care unit stay or death. Although standard treatment procedures are well known and seem to be sufficient at the first glance, there is need for improvement of therapy guidelines due to high rates of recurrences or treatment failures. This article suggests some adjustments so far without claiming to be a complete review of all new development in this area. On the one hand, the recent actualization of the European guideline has been taken as a basis of this report; on the other hand some new highly promising developments in the treatment of CDI are exemplarily reported. Possibly the development with the highest impact in literature is fecal transplantation (or better said microbiome instillation). However, standard therapies need some critical review as well: an upgrading of vancomycin to first line therapy and with a higher daily dose (250 mg qid) might be beneficial for many patients. For severe CDI, there is a recommendation against the usage of metronidazole, since vancomycin represents a better alternative. The dosage ofvancomycin might be further increased: although some authors are precautious in this point, dosage of vancomycin 500 mg qid should be favored. Last but not least, the pipeline bears some good tools for treatment of recurrent and complicated CDI, first data are promising and we hope for more. PMID- 26364373 TI - [Electronic-prescribing. A brief overview]. PMID- 26364374 TI - [Electronic drug prescription - auto pilot for drug therapy?]. AB - In tertiary care, computerized physician order entries may improve performance, cross-linking, and documentation when prescribing drugs. A clinical decision support integrated in these systems is discussed to prevent additional medication errors. For an optimal performance, the implementation into the clinical information systems is required to gain access to patient data (e. g. from laboratory). In routine care, the question rises whether a benefit of the systems can be proven in clinical studies and whether there is a difference between the systems. To achieve optimal results, these systems should also consider specific requirements, i. e. the patient groups and prescribed drugs in the local setting. We performed a systematic literature evaluation searching for published data in the topic electronic prescribing to assess them in a structured analysis considering medical-pharmaceutical aspects. Additionally, we assessed three databases in German language and one in English language taking drug-drug interactions as an example to compare the identification of drug-related problems. Medication data from our own patients in a paediatric intensive care unit of a university hospital were analysed by the systems. Our results revealed strengths but also limitations of electronic prescribing. PMID- 26364376 TI - [What will bring new therapeutic strategies and concepts of disease in asthma and COPD?]. PMID- 26364375 TI - [Why bother with regression models?]. AB - In the last article, you learned about the interpretation of survival curves. This article is about the comparison of "survival" - or the time to any defined event. Two survival curves can be summarized with the hazard ratio, which is discussed in more detail in this article. In order to compare the "survival"of two treatment groups - particularly in non-randomised studies - additional variables (potential confounders) must be taken into account. This is done using a regression model, the so-called Cox-regression. After reading this article, hopefully these terms are more familiar to you. PMID- 26364377 TI - [Substitution exclusion of inhalatives]. PMID- 26364379 TI - [Our expertise is in demand]. PMID- 26364380 TI - [Treatment of arterial hypertension in children and adolescents--Update of therapeutic options]. AB - Changing living conditions, which lead to physical inactivity and obesity, are probably the main reason for the establishment of risk factors for cardiovascular diseases in children and adolescents. In the past those risk factors were typically seen only in the elderly. On long-term, the elevated body-mass-index is a very important risk factor for primary arterial hypertension in children and adolescents, because it is responsible for both structural and functional changes in the cardiovascular system. Regular screening for these target organ damages is necessary. However, the role of newer methods has still to be proven in current research. The primary therapeutical options for this group are life style interventions like body weight control and physical activity. Children and adolescents with arterial hypertension persisting despite life style interventions should receive medication early, in order to prevent persistent target organ damage. Drug therapy should start as mono therapy--depending on patient profile--with one ACE inhibitor, angiotensin II receptor antagonist, calcium channel blocker or beta-blocker. If blood pressure cannot be reduced into the target area by mono therapy, combination therapy with different mechanisms should be started. Forms of secondary arterial hypertension have to be treated according to the primary disease. PMID- 26364382 TI - [About the certainty of study results. What p-value and confidence intervalls tell us on it]. AB - In clinical trials data of individuals are collected, who are subjected to different treatments under controlled conditions. These studies investigate differences between interventions, and their results--provide the basis for clinical decision making in individuals or for policy decisions concerning entire patient populations. This requires reliable results. How confident a result of the study actually is, is illustrated by using various statistical parameters: p value or confidence interval. What these parameters are and how to interpret them, is the objective of this article. PMID- 26364381 TI - [Comprehensive medication analysis in a multi-morbid patients with chronic renal failure]. PMID- 26364383 TI - [Reduction of consumption as the first goal of therapy]. PMID- 26364384 TI - [Hyaluronidase addition brings benefits]. PMID- 26364385 TI - [Denosumab finds its way into the updated DVO guidelines]. PMID- 26364386 TI - [What methotrexate dose is optimal in combination with adalimumab?]. PMID- 26364387 TI - [Flupirtine helps - but pay attention to the liver!]. PMID- 26364388 TI - [New galenics increased tacrolimus bioavailability]. PMID- 26364389 TI - [Preventive role of specific immunoglobulins]. PMID- 26364390 TI - [Inhaled antibiotic use]. PMID- 26364392 TI - [Intoxicating self-medication]. PMID- 26364391 TI - [Basal insulin and liraglutide combined in a pen]. PMID- 26364393 TI - [Sweeteners - a risk factor for type 2 diabetes?]. PMID- 26364394 TI - [New drugs--chemical, pharmacological, metabolical, analytical and legal aspects]. AB - The characterisation of new psychoactive drugs which were identified in the last years in continuously increasing numbers is a challenge for different academic institutions. This paper gives an overview on new psychoactive drugs in regard of their chemistry, pharmacology, metabolism, analytics and legal aspects in Germany. PMID- 26364396 TI - [The number needed to treat (NNT) and the number needed to harm (NNH)]. AB - In our previous articles we introduced the relative and absolute expressions of risk: baseline risk, relative risk (RR), relative risk reduction (RRR), absolute risk reduction (ARR), or risk difference (RD). The "number needed to xy" is another concept to describe the results of a clinical trial. Depending on the investigated problem the "number needed to xy" is the "number needed to treat", the "number needed to harm", the "number needed to vaccinate", or the "number needed to screen". In this article of our series we introduce the number needed to treat (NNT) and the number needed to harm (NNH) as a method to characterize the difference of two compared therapy options. As the other effect sizes the NNT and NNH can be used to inform patients about the expected benefit (or harm) of different therapy options. PMID- 26364395 TI - [Treatment of intoxication with new psychoactive substances and methamphetamine]. AB - Fatal outcomes subsequent to the use of new psychoactive suostances are increasingly common in Germany. In this article, we present the clinical effects and associated side effects of the different classes of substances, as synthetic cannabinoids, synthetic cathinones, phenylethylamines, piperazines and methamphetamine, as well as diagnostic aspects and treatment options in case of symptoms of poisoning. PMID- 26364397 TI - [When is an iodine - substitution useful when counter-productive?]. PMID- 26364398 TI - [Discussion on the right estimation formula]. PMID- 26364399 TI - [Triptans are not teratogenic]. PMID- 26364400 TI - [Soft and gentle anesthesia]. PMID- 26364401 TI - [Effectiveness and tolerability of opioids for non-cancer pain]. PMID- 26364403 TI - [Long-term treatment of venous thromboembolism and prevention of relapse in cancer patients]. PMID- 26364402 TI - [Is colchicine suitable for prevention?]. PMID- 26364404 TI - [Scene of the crime. Liver]. PMID- 26364406 TI - [Nonalcoholic fatty liver disease. Pathophysiologically oriented diagnosis and therapy]. PMID- 26364405 TI - [Options in the treatment of hepatic encephalopathy]. AB - Hepatic encephalopathy is a result of insufficient liver function, with grave consequences for the patients. It is primarily caused by disturbed hepatic elimination of the neurotoxin, ammonia (NH3). Aside from dietetic measures, treatment rests on drugs designed to reduce the NH3 burden. The primary options, lactulose and the practically unabsorbable antibiotic rifaximin are suitable to decrease the bacterial NH3 generation in the intestine. Other antibiotics like neomycin at best have a place in acute treatment. L-ornithine-L-aspartate (LOLA) and branched-chain amino acids (valine, leucine, isoleucine) aim at supporting the scavenge of NH3 in glutamine; however, the final balance of this pathway is unfavourable. In addition, the constituents of LOLA enhance the capacity of the urea cycle and, ultimately, the elimination of NH3. As the evidence from available studies--is not unequivocal in each case, the current place of LOLA in treatment is that of an option for patients, who do not respond to standard therapy. PMID- 26364407 TI - [The fight against measles--problems on the road to elimination]. AB - Measles is a highly contagious viral disease that is associated with life threatening complications, especially in infants (<1 year) and adults. In the fight against measles, immunoprophylaxis is of crucial importance. By vaccination, in recent decades the incidence of the disease has been significantly reduced worldwide. In order to achieve global measles elimination in 2020, in many countries current epidemic transmission chains must be permanently broken. In addition, a significant reduction in measles incidence through higher vaccination rates must be achieved. PMID- 26364408 TI - [Painting by number--Survival curves and Kaplan-Meier method]. AB - Survival curves plot percent survival as a function of time. Results of clinical trials are often presented as survival curves. However, the purpose of survival analysis is not, as the name suggests, limited to "survival". Rather, it can concern the time to any defined event, desired or undesired. The me- thod behind these curves may be tricky; "reading" of the curves, however, is simple and intuitive. And with a few basic skills misinterpretations can usually be avoided. PMID- 26364409 TI - [There is medical optimism]. PMID- 26364410 TI - [Pasireotide as a new second-line treatment option]. PMID- 26364411 TI - [New hypodermic syringe improves administration quality]. PMID- 26364412 TI - [Bone density measurements after alendronate therapy?]. PMID- 26364413 TI - [Early intensive treatment reduces long-term mortality]. PMID- 26364414 TI - [Dulaglutide and liraglutide compared]. PMID- 26364415 TI - [HIV treatment and prevention]. PMID- 26364416 TI - TINY RESUSCITATION. A Facebook posting brings back precious EMS memory. PMID- 26364417 TI - QUESTIONABLE STATISTIC. PMID- 26364418 TI - EMS EPCRS. PMID- 26364419 TI - AUTHOR VICTORIA BRADLEE, PA-C, MHS, BS, EMT-B, RESPONDS. PMID- 26364420 TI - ROLE-PLAY. Using simulation to teach management skills. PMID- 26364421 TI - NOTICING NEGLECT. EMS is positioned to recognize & report potential abuse or maltreatment. PMID- 26364422 TI - IMPALED & OBESE. Trauma isn't always the most important aspect at the scene. PMID- 26364423 TI - ABUSE BARRIER. Providers don't know when to report child abuse. PMID- 26364425 TI - STATION-FRIENDLY WORKOUTS. Five exercises easily done at work. PMID- 26364426 TI - D.I.Y. INJURIES. A do-it-yourself guide to inexpensive, reusable simulation manikin moulage. PMID- 26364424 TI - Perils of SUMMER. How to treat pediatric summertime emergencies. PMID- 26364427 TI - CLOSING THE GAPS. Helping patients navigate the healthcare system in Baton Rouge, La. PMID- 26364428 TI - TOTAL QUALITY MANAGEMENT. Richmond Ambulance Authority uses technology to enhance its QA/QI process. PMID- 26364429 TI - Legal Highs. Learn how to identify & treat patients under the influence of so called legal substances of abuse. PMID- 26364430 TI - QUANTIFYING DIRECTORS. How much medical direction do we need? PMID- 26364431 TI - How Do I Know If My Dental Website Is Mobile-Friendly? PMID- 26364432 TI - How to Respond to a Negative Review. PMID- 26364433 TI - Ebola: Lessons Learned. PMID- 26364434 TI - The Internet as a Healthcare Advocate. PMID- 26364435 TI - Vision and the Coming of Age. PMID- 26364436 TI - Ebola Virus Disease. Resources and Guidance from the CDC. PMID- 26364437 TI - Helping Your Managers Manage: The Hallmarks of Superior Supervision. PMID- 26364438 TI - Federal Funding to Meet the Demands of Our Nation's Health-Care Needs Why Is This Year So Important? PMID- 26364439 TI - Meredith Winkler, RN, MSN, CRNO. PMID- 26364440 TI - [The teaching of occupational medicine in the Master of Science in Medicine in the twenty years since the introduction of Table XVIII]. AB - In 1991, the implementation of the new programme for education and training in Medicine and Surgery has introduced the teaching of Occupational Medicine (OM) as a compulsory subject for all medical students. After two decades from that event and in conjunction with the implementation of the new academic departments introduced by the law 240/2010, the aim of the present study was to address the current status and the main characteristics of education and training, including clinical activities, in OM in Italian Universities and to update the information on the related academic human resources available. A questionnaire was developed to investigate the different features of the academic staff belonging to the area of OM (SSD MED/44), and to evaluate the organization of teaching and the clinical activities performed by the Occupational Medicine sections. The results showed that among the 40 Italian universities with a degree course in Medicine and Surgery, 67% of them have at least one full professor, 72% one associate professor and 78% one assistant professor belonging to the area of OM. Nevertheless, a steady decrease in the number of academic staff is observed with time, which caused a lack of presence of the discipline in some universities. In most degree courses in Medicine and Surgery the teaching of OM is usually included in an integrated course together with other disciplines such as General and Applied Hygiene and/or Forensic and Legal Medicine. Within the integrated course the number of University Education & Training Credits (CFU, corresponding to approx. 25 hrs of teaching overall) assigned to OM is generally between 2 and 3 (61% of cases). The teaching of OM is also present in eight different master degree courses (MSc) and in 33 different triennial degree courses (BSc). To support the teaching clinical activities, such as workers' health surveillance, laboratories, ambulatories, and DH or inpatient activities are performed, in one or more of these forms, by almost all of the OM institutions. The findings of this study, despite being subject to change rapidly with time, still provide an invaluable set of information and should represent, therefore, a rational basis for planning the future recruitment of academic staff and for updating the contents and methodologies of graduate education and training in Occupational Medicine in Italian universities. PMID- 26364442 TI - [Health surveillance for employees who work in "areas suspected of pollution" or confined]. AB - About medical aspects related to the work involving confined spaces Neil McManus, one of the leading world expert on the topic, points out that now a days, besides what is required for general work environmental, no specific data can be found in the literature on health surveillance programs for workers engaged in activities in confined environments. Although there are activities in confined environments, which may include the adoption of operating procedures and protection systems similar to those one used in manufacturing jobs (e.g., use of PPE as respiratory mask and protective clothing, etc.) we must, however, emphasize that activities in confined environments involve specific working conditions of particular physical / psychological stress for employees. Working in these spaces has as consequences issues not found in other situations (being confined, difficulties in the movement, unable to access / exit, uncomfortable postures, etc.) and also, in emergency, it may involve difficulties with activities offirst aid or extraction of the worker injured and in some cases even obstruct them. Therefore we believe that it is important to begin a debate on the topic and to indicate what should be the physical requirements of the employees who have been called to work in this particular workplace. PMID- 26364441 TI - [DIFFERENT APPROACHES FOR CHEMICAL RISK ASSESSMENT IN LABORATORIES]. AB - The aim of this study was to compare the different approaches used for chemical risk assessment, in relation to the perception of riskfor operators, in some research laboratories of a hospital in Rome. All information regarding the chemicals used for the application of three algorithmic models for chemical risk assessment ("Movarisch", "Inforisk", "Archimede") were collected. An environmental and biological monitoring and a study on the combined exposure to multiple chemicals using the World Health Organization proposed steps were carried out. A questionnaire was prepared for the identification of risk perception. An estimation of chemical risk with algorithms was compared with data from monitoring: findings showed that estimated risk was higher than those identified with airborne or urine concentrations, always under their limit values. The study of multiple exposure showed a possible cumulative risk, in some cases, but the conditions of use (volume and time) often bring to a reduced one. The perception of risk attributed to the monitored hazardous substances showed a correct perception in all laboratories and for all workers, with regard to the substances manipulated. PMID- 26364443 TI - [Health issues and regulatory aspects of the use of ultrasound in physiotherapy]. AB - The use of ultrasounds in medicine requires, like all physical agents potentially harmful to human health, an accurate assessment of the risks to the health of patients. The nature and extent of these risks depend on exposure levels which in turn are differentiated according to the specific diagnostic or therapeutic applications. Intermediate exposure levels are associated to physiotherapic applications. To analyze specific issues relating to the effectiveness and safety of physiotherapic treatments, a review of the scientific literature and technical standards was carried out. At present, the actual effectiveness of ultrasound physiotherapy is still far from being clearly assessed: further clinical and experimental studies are needed in order to optimize therapies, determining the benefits and risks of treatments and deepening the understanding of the action mechanisms of the physical agent, even on the basis of a better characterization of those physical quantities mostly significant for biological effects. The examination of technical standards defining the security requirements of the equipment allowed the identification of some critical issues; on these bases some proposals are suggested for the improvement of quality and safety of treatments. PMID- 26364444 TI - [ANALYSIS OF A NEW ORGANIZATIONAL MODEL APPLIED TO THE PHYSIOTERAPY SERVICE C/O SURGERY DEPARTMENTS]. AB - The lowering number of physiotherapists c/o surgery departments of Orthopaedic Institute Gaetano Pini of Milan, required the application of a new organizational model based on the centralization of government activities, in order to optimize employment of staff. A programming and reporting tool was developed throught a database. The collected data (from January to December 2013) related to the reported physiotherapists activities were analysed and matched to operating theater's activities in order to find the correlation value. The results are lined up the hypothesis stated in the planning phase of the organizational model's project (in absence of hystorical referral). Correlation between Physiotherapists and Operation Theather's activities was good (r=0.59), giving us a reliable predictional model. This study has some limitations mostly related to the resistence expressed by employees in the change management. PMID- 26364445 TI - [CROSS-CULTURAL ADAPTATION, AND VALIDITY OF THE ITALIAN VERSION OF THE UPPER LiMB FUNCTIONAL INDEx (ULFI-I)]. AB - BACKGROUND: Outcome measures are the scientific basis for assessment and comparison of the effects of rehabilitative interventions. Among the instruments proposed for the evaluation of musculoskeletal disorders of the upper limb, the Upper Limb Functional Index (ULFI) was recently validated and translated into several languages, but it does not yet exist an Italian version yet. OBJECTIVE: To obtain an Italian validated version of ULFI, called ULFI-I. MATERIALS & METHODS: The translation process was conducted following the international guidelines of the forwardlbackward translation. The ULFI-I was subsequently validated by calculating: (1) internal consistency (Cronbach's a and item-to total correlation), (2) criterion validity (correlation r with the Disabilities of the Arm, Shoulder and Hand Questionnaire, DASH), and (3) test-retest reliability (ICC(2,1)) and measurement error (Standard Error of measurement, SEM and Minimal Detectable Change, MDC90. For the first two points we used a sample of 57 patients with upper limb orthopedic conditions, while the analysis of the. reliability required a further administration of the questionnaire carried out 3 days before on 33 subjects. I. Statistical analysis showed good levels of internal consistency (Cronbach's alpha=.90, item-to-total correlation between .45 and .73), high criterion validity (r=.81, P<0.01) and excellent reliability test retest reliability (ICC(2,1)=.94, CI=.89-.97). The SEM was found to be equal to 5 points, with a MDC90 estimated at 12 points. CONCLUSION: In this study the ULFI-I showed good psychometric properties, combined with speed and ease of administration and scoring. Its use will facilitate the comparison of data collected in Italy with international studies, ensuring greater uniformity of assessment. PMID- 26364446 TI - [STRESS DUE TO THE WORK-LIFE CONFLICT: ADVICES FROM APPLIED RESEARCH FOR COPING IT]. AB - Unlike most of the work-related stress research, which emphasizes how to manage stressors and maximize the psychological well-being, the present article focuses on one particular kind of stressor: the experience of conflict or interference between demands at work and responsibilities and commitments outside of the work setting, especially in respect offamily life and one's personal life. Referred to as "work-family conflict" or (more recently) "work-life conflict", this stressor has been demonstrated in research since the 1990s to exert a considerable impact on individuals' well-being along with other areas such as family functioning and even performance on the job. In contrast to the intra-role conflict, which refers to interference between roles within a single domain (e.g., the work context), work-family (or work-life) conflict is a form of inter-role interference which occurs when there is conflict across domains. In the 1980s and 1990s, research and writing in this area focused predominantly on work versus family, but in recent years the "non-work" component has been expanded to include other aspects of people's lives. For simplicity, we will refer to the two major spheres as the "work domain" (i.e., a person's paid employment) and the "life domain" (which comprises all other dimensions of life, including family, recreation, community activities and personal life). Although this classification is not entirely appropriate, it enables differentiation between the two spheres. PMID- 26364447 TI - Viral hepatitis today. PMID- 26364448 TI - The impact of an educational film on promoting knowledge and attitudes toward HIV in soldiers of the Serbian Armed Forces. AB - BACKGROUND/AIM: Millions of soldiers around the world represent one of the most vulnerable populations regarding exposure to human immunodeficiency virus (HIV) infection. The programs for HIV prevention remain the most viable approach to reducing the spread of HIV infection. Very few studies have tested the effectiveness of HIV preventive interventions undertaken in military population. The aim of this study was to determine the effectiveness of educational film to transfer knowledge about HIV infection to soldiers. METHODS: We performed a quasi experimental study among 102 soldiers of the Serbian Armed Forces. The experimental intervention consisted of the HIV knowledge pre-questionnaire, watching a film on HIV knowledge, then the post-HIV knowledge questionnaire. The results of pre- and post-HIV knowledge questionnaires were compared. RESULTS: There were 23 questions in the test. The average total score on the questionnaire before watching the film was 18.23 and after watching it was 20.14, which was statistically significant difference (p < 0.001). CONCLU- SIONS: The results of the study show that viewing a film on HIV infection is an effective method of transferring knowledge about HIV to the Serbian military population. PMID- 26364449 TI - Treatment of stable and unstable intertrochanteric fractures with selfdynamisable internal fixator (concept of double dynamisation). AB - BACGROUND/AIM. Intertrochanteric fractures of the femur are the third most common fractures among all bone fractures. Today in everyday orthopedic practice a number of different methods of treatment of trochanteric fractures of the femur are applied. Despite the improvement in the development of new implants, the percentage of serious complications of the treatment of these fractures remains very high, varying from 10% to 20%. One of the most serious complications of internal fixation of intertrochanteric fractures is nonunion of fractures due to the lack of additional axial dynamisation of implants. The aim of this study was to determine the efficacy of double dynamisation in stable and unstable intertrochanteric fractures treatment using the self dynamisable internal fixator. METHODS: During the period from 2000 to 2009 we analyzed the use of selfdynamisable internal fixator (SIF implant) in the treatment of 247 patients with stable and unstable intertrochanteric fractures. Fracture types were classified according to the AO Fracture Classification/Orthopaedic Trauma Association Scheme. Salvati and Wilson scoring systems were used for functional assessment considering pain, walking ability and hip movements of operated patients. RESULTS: Of the total number of treated patients, 134 were males and 113 females, aged 19 to 90 (average 49.6) years. More than a half of the patients were older than 50 years. Monitoring of the patients after the operation was carried out clinically and radiographically for a period of three to six months in all the patients, whereas a 2-year follow-up was conducted in 176 (71.2%) patients. The average duration of surgery was 47 min, the average blood loss 145 mL, and the average fluoroscopy time was 16 sec (8-97 sec). The average time for union was 3.7 months (3-6.6 months). Double dynamisation (dynamisation along the neck and shaft of the femur) was observed in 85 (34.4%) patients, and was on average 4.3 mm (1.5-8 mm). All fractures managed with dynamisation implants healed completely within no later than six months after the surgery. In 17 cases there was a cut-out phenomenon of implant, while in seven cases there was mechanical implant failure. Complications were detected within 3 to 6 weeks after surgery, and treated by the method of intramedullary fixation. During the study, there were no cases of infection and thromboembolic complications detected. CONCLUSION: The concept of double dynamisation improves the fracture healing in the stable and unstable intertrochangeric fractures using the selfdynamisable internal fixator. This biological method of fixation provides healing of intertrochanteric fracture in the optimum period of time, significantly reducing the risk for mechanical failure. PMID- 26364450 TI - Validation and cross-cultural adaptation of the questionnaire ThyPRO in thyroid patients in Serbia. AB - BACKGRAUND/AIM: The Thyroid Specific Patient Reported Outcome Measure (ThyPRO) questionnaire is self-administered and intended to measure quality of life of thyroid patients. The aim of this study was to investigate the validity and reliability of the translated new, ThyPRO questionnaire in Serbian patients with thyroid disease. METHODS: The translation process followed an internationally accepted methodology. The questionnaire was validated in 100 consecutive thyroid patients hospitalized in a tertiary level hospital, between April and August 2012. Internal reliabilities of ThyPRO scales were assesessed using Cronbach's alpha coefficient. Association between age, gender, education, marital and employment status, place of living, diagnosis, current treatment, hormonal status and patient quality of life were determined using Pearson's (r) and Spearman's (q) correlation coefficients. RESULTS: Internal consistency and reliability for ThyPRO scales were satisfactory. Cronbach's alpha coefficients of 13 multi-item scales of the ThyPRO were > 0.83 (range 0.83-0.95). The scores, obtained by this questionnaire, correlated significantly with patients gender, employment status, diagnosis, current treatment and place of living. A highly significant inverse relationship was found between scores and hormonal status as well as between scores and disease duration. Patients' age, marital status and thyroid stimulating hormone level did not influence any scale score. CONCLUSION: The ThyPRO may be useful in measuring health-related quality of life in patients with thyroid disease in Serbia. PMID- 26364451 TI - Incidence, predictors and prognostic implications of bleeding complicating primary percutaneous coronary intervention. AB - BACKGROUND/AIM: Data about bleeding complicating primary percutaneous coronary intervention (PCI) are more frequently obtained from randomized clinical trials on patients with acute coronary syndromes (ACS), but less frequently from surveys or registries on patients with ST-elevation myocardial infarction (STEMI). The aim of this study was to investigate the incidence, predictors and prognostic impact of in-hospital major bleeding in the population of unselected real-world patients with acute STEMI undergoing primary PCI. METHODS: All consecutive patients presenting with STEMI who underwent primary PCI at a single large tertiary healthcare center between January 2005 and July 2009, were studied. Major bleeding was defined according to the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) study criteria. We examined the association between in-hospital major bleeding and death or major adverse cardiac events (MACE) in patients treated with PCI. The primary outcomes were in-hospital and 6 month mortality and MACE. RESULTS: Of the 770 STEMI patients treated with primary PCI, in-hospital major bleeding occurred in 32 (4.2%) patients. Independent pre dictors of major bleeding were advanced age (>= 65 years), female gender, baseline anemia and elevated white blood cell (WBC) count and signs of congestive heart failure at admission (Killip class II-IV). In-hospital and 6 month mortality and MACE, rates were more than 2.5-fold-higher in patients who developed major bleeding compared with those who did not. Major bleeding was predictor of 6-month MACE, independent of a few risk factors (previous MI, previous PCI, diabetes mellitus and hypertension); (OR = 3.02; 95% CI for OR 1.20 7.61; p = 0.019) but was not a true independent predictor of MACE and mortality in the fully adjusted models. CONCLUSION: Patients of advanced age, female gender, with baseline anemia and elevated WBC count and those with Killip class II-IV at presentation are at particularly high risk of bleeding after primary PCI. Bleeding is associated with adverse outcome and may be an important marker of patient frailty, but it is not a true independent predictor of mortality/MACE. PMID- 26364452 TI - The clinical course of non-muscle invasive bladder cancer after transurethral resection of the tumor with or without subsequent intravesical application of bacillus Calmette-Guerin: The influence of patients gender and age. AB - BACGROUND/AIM: The therapy with intravesical instillation of bacillus Calmette Guerin (BCG) after transurethral resection (TUR) of tumor is the gold standard of treatment of non-muscle invasive bladder cancer (NMIBC). The role and importance of BCG intravesical therapy in various shape of tumors, were confirmed by our previous investigation. The aim of this study was to examine whether incidence of recurrence and tumor regression differs depending on sex and age of patients. METHODS: This study included a total of 899 patients suffering from NIMBC, treated at our institution from January 1, 2007 to March 1, 2013. Two groups of patients were formed: patients underwent TUR + BCG therapy (the group I) and the group II with patients in whom TUR was performed as only therapy. These two groups of patients were divided into subgroups of respondents male and female, age 60 years or younger and older than 60 years. Statistical analysis was performed using chi2 test and the Kolmogorov-Smirnov test. RESULTS: This research suggests that if the frequency of recurrence is seen as the only parameter, considering all the subjects, the lowest recurrence rate was determined in the male subjects, aged 60 years and younger who had received BCG after TUR. A high statistical significance was found in the incidence of recurrence in patients younger than 60 years, depending on the response to the therapy, while in those older than 60 years, the difference was at the level of statistical significance. This can be attributed to a certain degree of infravesical obstruction in older men. CONCLUSIONS: Sex and age of patients may have a significant influence on the course and outcome of NMIBC. The disease has the most malignant and most aggressive behavior when present in males older than 60 years. PMID- 26364453 TI - Reliability and validity of the Serbian version of Children's Dental Fear Questionnaire. AB - BACKGROUND/AIM: Dental anxiety leads to avoidance of dental treatment and could lead to impaired oral health. The aim of this study was to determine the reliability of the Serbian version of Children's Fear Survey Schedule Dental Subscale (CFSS-DS) and the relations between dental anxiety and oral health status in a sample of Serbian schoolchildren. METHODS: The CFSS-DS scale was translated into Serbian and administered to 231 (12-year old) patients of the Pediatric Dental Department, Public Health Center Cukarica, Belgrade. The number of healthy, decayed, missing and filled teeth (DMFT score) in children was determined by a clinical exam. RESULTS: The average CFSS-DS score was 26.47 +/- 10.33. The girls reported higher anxiety than the boys (p < 0.05). Most common fears were drilling, choking, going to the hospital and anesthesia. Lower CFSS-DS scores were recorded in children with all healthy teeth (p < 0.05). Children with higher CFSS-DS scores mostly visit the dentist due to pain or parental insistence, and those with lower anxiety scores more often visited dentist due to regular check-ups or non-invasive treatments (p < 0.01). A high value of the Cronbach's coefficient of internal consistency (alpha = 0.88) was found in the entire scale. CONCLUSION: The Serbian version of CFSS-DS questionnaire is reliable and valid psychometric instrument for evaluation of dental fear in Serbian children. Dental anxiety negatively affects dental attendance and oral health of the examined schoolchildren. PMID- 26364454 TI - Clinical significance of soluble Fas plasma levels in patients with sepsis. AB - BACKGROUND/AIM: The goal of modern clinical and experimental researches in the field of sepsis is to find one or more sensitive parameters that could predict the severity of sepsis and its outcome. In this study we investigated and compared the relationship of initial soluble Fas (sFas) plasma levels as well as Acute Physiology, Age and Chronic Health Evaluation II (APACHE II) score in 58 septic patients with severity and outcome of sepsis. METHODS: The diagnosis and assessment of disease severity was performed on the same day, based on clinical and laboratory parameters. The blood samples were used for monitoring of laboratory standard parameters necessary for the diagnosis of sepsis, organ dysfunction and assessment of disease severity, as well as for determination of levels of sFas. According to consensus criteria, patients were divided into those with sepsis (n = 16), severe sepsis (n = 30) or septic shock (n = 12), those with (n = 26) and without (n = 32) multiple organ dysfunction syndrome (MODS), and survivors (n = 45) and nonsurvivors (n = 13). RESULTS: Plasma sFas level (9.7 +/- 10.1; 0-44.2 U/mL) was elevated in 54.4% of patients. All the patients with septic shock, 76.9% of the patients with MODS and 84.6% patients who died had elevated sFas level. We observed a strong positive correlation between sFas and APACHE II score (p < 0.001). The level of sFas was significantly higher in patients with septic shock compared to normotensive patients (p < 0.001), patients with MODS compared to those without MODS (p < 0.001) and survivors compared to nonsurvivors (p < 0.01). CONCLUSIONS: Our results suggest that initial sFas plasma levels in patients with sepsis correlated with the values of APACHE II score and separated very well the patients with septic shock versus the normotensive patients, the patients with and without MODS, and survivors versus nonsurvivors. PMID- 26364455 TI - Different techniques of vessel reconstruction during kidney transplantation. AB - BACKGROUND/AIM: Multiple renal arteries (MRAs) represent a surgical challenge by the difficulty in performing anastomoses, bleeding and stenosis. MRAs should be preserved and special attention should be paid to accessory polar arteries. All renal arteries (RAs) must be reconstructed and prepared for safe anastomosis. The paper decribed the different techniques of vessel reconstruction during kidney transplantation including important steps within recovery of organs, preparation and implantation. METHODS: In a 16-year period (1996-2012) of kidney transplantation in the Military Medical Academy, Belgrade, a total of 310 living donors and 44 human cadaver kidney transplantations were performed, of which 28 (8%) kidneys had two or more RAs. RESULTS: All the transplanted kidneys had immediate function. We repaired 20 cases of donor kidneys with 2 arteries, 4 cases with three RAs, one case with 4 RAs, one case with 4 RAs and renal vein reconstruction, one case with 3 arteries and additional polytetrafluoroethylene (PTFE) graft reconstruction, one case with transected renal artery and reconstruction with 5 cm long deceased donor external iliac artery. There were no major complications and graft failure. At a minimum of 1-year follow-up, all the patients showed normal renal function. CONCLUSION: Donor kidney transplantation on a contralateral side and "end-to-end" anastomosis of the renal artery to the internal iliac artery (IA) is our standard procedure with satisfactory results. Renal artery reconstruction and anastomosis with IIA is a safe and highly efficient procedure and kidneys with MRAs are not contraindicated for transplantation. A surgical team should be fully competent to remove cadaveric abdominal organs to avoid accidental injuries of organs vessels. PMID- 26364456 TI - Multidisciplinary approach to nitric oxide signaling: Focus on the gastrointestinal and the central nervous system. PMID- 26364457 TI - Current concepts of radioimmonotherapy for lymphoma. PMID- 26364458 TI - Decompression as an effective primary approach to large radicular cyst in the maxillary sinus--A case report. AB - INTRODUCTION: Therapeutic approach to jaw cysts may depend on their dimensions and localization. Enucleation of cystic lesion is not always preferable in the first act, especially if large cysts are in close proximity to important anatomical structures. The aim of this paper was to present the outcome of the treatment protocol comprising preoperative decompression and subsequent enucleation of a large maxillary cyst. CASE REPORT: A 21-year-old male patient with large asymptomatic radicular cyst in the right maxillary sinus was presented to our clinic. Cone-beam computed tomography (CBCT) showed a large cyst, which perforated the right anterior maxillary wall by 1.5 cm, and was in the intimate contact with the orbital floor. Surgical treatment of the cystic lesion comprised: preoperative decompression with biopsy in the first act and enucleation, performed under general anesthesia, 6 months after the observation period. CONCLUSION: Decompression with subsequent enucleation proved to be effective treatment of large radicular cyst in maxillary sinus with low morbidity. PMID- 26364459 TI - A misdiagnosed myasthenia gravis with anti-muscle-specific tyrosine kinase antibodies with possible childhood onset. AB - INTRODUCTION: Childhood onset myasthenia gravis associated with anti-muscle specific tyrosine kinase antibodies is very rare and atypical in presentation. CASE REPORT: As a baby, the pre- sented patient was choking and sleeping with open eyes. She had weak cry and breathing difficulties. In childhood, there were fre- quent falls and fluctuating swallowing difficulties. At the age of 19 she was misdiagnosed with Miller Fisher syndrome due to the presence of diplopia, ataxia and hyporeflexia with spontaneous recovery. Repetitive nerve stimulation test was normal. Four years later, after several relapses, there was significant decrement on facial muscles. Neostigmine test was negative, provoking muscle fasciculations. Serum anti-muscle-specific tyrosine kinase antibodies were positive. With cyclosporine therapy she achieved the minimal manifestations status. CONCLUSION: The presented case confirms that childhood onset myasthenia gravis associated with anti-muscle-specific tyrosine kinase antibodies is often with atypical presentation and spontaneous remissions, so it could be easily misdiagnosed. PMID- 26364460 TI - Synchronous gastric and colonic cancer--A case report. AB - INTRODUCTION: Synchronous gastric and colorectal cancer is present in 4% of cases, commonly as additional finding. This is the case of invasive, synchronous gastric and sigmoid colon cancer. CASE REPORT: A 63-years-old male patient admitted to our institution complaining on pains in epigastrium, vomiting, rapid weight loss and occasional constipation. Using the method of esophagogastroduodenoscopy (EGD) the presence of ulcero-infiltrative tumor of gastric fundus was verified, and colonoscopy revealed stenosing tumor of sigmoid colon. Undergoing a multislice computed tomography (MSCI) of the thorax and the abdomen the changes on the patient's right lung appeared, while video-assisted thoracoscopy (VATS) and biopsy of the right lung excluded malignant dissemination. A total gastrectomy with omentectomy, splenectomy, D2 lymphadenectomy and typical left hemicolectomy were also performed. Histopathological examination verified invasive, diffuse gastric adenocarcinoma and invasive, tubular colon adenocarcinoma. The patient underwent systemic postoperative chemotherapy. Two years after the surgical procedure, the patient is alive, with no signs of recidivism. CONCLUSION: In patients with symptomatology which does not correspond to primary malignancy, just like in the presented case, additional diagnostics is required. Combined resection is adequate surgical procedure for synchronous gastric and colonic cancer. PMID- 26364461 TI - The effect of whole-body vibration and resistance training on muscle strength in a 13-year-old boy with m. biceps femoris lesion and posttraumatic calcification. AB - INTRODUCTION: Skeletal muscle atrophy is a common adaptation after major muscle lesion of m. biceps femoris that results in numerous health-sport related complications. Resistance strength training and whole-body vibration (WBV) have been recognized as an effective tool, which attenuates atrophy and evokes hypertrophy. CASE REPORT. We presented a 13-year-old boy with a lesion of m. biceps femoris and post-traumatic calcification sustained in soccer training session 6 month prior participation in this study. The patient underwent training 3 times a week for 7 weeks, including unilateral progressive WBV + resistance training (RT) of the right hamstrings muscle group using WBV and weights. Hamstrings muscle strength was measured using a Cybex isokinetic dynamometer. At the end of week 4, the patient peak torque value of the involved leg increased from 39% body weight (BW) to 72% BW and bilateral deficit decreased from -64% to 35%; at the end of week 7 the participant's peak torque value of the involved leg increased from 72% BW to 98% BW and bilateral deficit decreased from -35% to -3%, respectively. CONCLUSION: Unilateral WBV + RT protocol evokes strength increase in the hamstrings muscle group. This case study suggests that adding WBV, as well as the RT program have to be considered in the total management of strength disbalance. Further studies are needed to verify the efficiency of WBV + RT protocol over the classic physical therapy exercise program. PMID- 26364462 TI - Cervical poorly differentiated adenocarcinoma with dominant choriocarcinomatous pattern--A case report. AB - INTRODUCTION: Gestational trophoblastic neoplasm (GTN), choriocarcinoma in coexistence with primary cervical adenocarcinoma, is a rare event not easy to diagnose. Choriocarcinoma is a malignant form of GTN but curable if metastases do not appear early and spread fast. CASE REPORT: We presented choriocarcinoma in coexistence with primary cervical adenocarcinoma in a 48-year-old patient who had radical hysterectomy because of confirmed cervical carcinoma (Dg: Carcinomaporo vaginalis uteri FIGO st I B1). Histological findings confirmed cervical choriocarcinoma with extensive vascular invasion and apoptosis but GTN choriocarcinoma was finally confirmed after immunohystochemical examinations. Preoperative serum human gonadotropine (beta hCG) level stayed unknown. This patient did not have any pregnancy-like symptoms before the operation. The first beta hCG monitoring was done two months after the operation and found negative. According to the final diagnosis the decision of Consilium for Malignant Diseases was that this patient needed serum hCG monitoring as well as treatment with chemotherapy for high-risk GTN and consequent irradiation for adenocarcinoma. CONCLUSION: The early and proper diagnosis of nonmetastatic choriocarcinoma of nongestational origine in coexistence with cervical carcinoma is curable and can have good prognosis. PMID- 26364463 TI - Effect of cold water and inverse lighting on growth performance of broiler chickens under extreme heat stress. AB - The present study was carried out to investigate the effect of provision of extreme heat stress diet (EHD), inverse lighting, cold water on growth performance of broiler chickens exposed to extreme heat stress. The chickens were divided into four treatment groups, (T1, T2, T3, T4) as given below: Ti (EHD 1, 10:00-19:00 dark, 19:00-10:00 light, cool water 9 degrees C); T2 (EHD 2, 10:00 19:00 dark, 19:00-10:00 light, cool water 9 degrees C); T3 (EHD 1, 09:00-18:00 dark, 18:00-09:00 light, cool water 141C); T4 (EHD 2, 09:00-18:00 dark, 18:00 09:00 light, cool water 14 degrees C. EHD 1 contained soybean oil, molasses, methionine and lysine; EHD 2 contained the same ingredients as EHD 1 with addition of vitamin C. Groups T1 and T2 were given cooler water than the othertwo groups, and displayed higher body weight increase and diet intake as compared to T3 and T4 (p<0.05). The weights of their liver and gizzard were similar but the weights of the thymus and bursa of fabricius (F) were higher in groups T1 and T2 (p<0.05). It was observed that groups T1 and T2 displayed higher concentrations of blood triglyceride, total cholesterol, HDL-cholesterol and blood sugar as compared to T3 and T4; however LDL-cholesterol level was higher in groups T3 and T4 (p<0.05). T1 and T2 displayed higher levels of immunity substances such as IgG, IgAand IgM as compared to T3 and T4, but the blood level of corticosterone was lower in groups T1 and T2 (p<0.05). Ti and T2 contained higher amount of fecal Lactobacill as compared to T3 and T4; howeverT3 and T4 contained higher amount of fecal E. coli, total aerobic bacteria and coliform bacteria (p<0.05). Groups T1 and T2 displayed higher concentrations of cecal total short chain fatty acids, acetic acid and propionic acid but groups T3 and T4 displayed higher concentrations of butyric acid, isobutyric acid, valeric acid and isovaleric acid (p<0.05). The present study reports novel results such that the supply of extreme heat stress diet, inverse lighting (10:00-19:00 dark, 19:00-10:00 light) with cold water at 9 degrees C under extreme heat stress could enhance growth performance of broiler chickens. PMID- 26364464 TI - Influence of drought stress on cellular ultrastructure and antioxidant system in tea cultivars with different drought sensitivities. AB - Drought is the major yield-limiting abiotic factor of tea cultivation. In the present study, influence of drought stress on cellular ultrastructure and antioxidants was studied drought-tolerant (TV-23) and -sensitive (S.3/A3) tea cultivars by imposing drought stress for 21 days. Drought stress led to considerable structural alterations in mitochondria, chloroplast and vacuole. Lesser membrane integrity and higher structural damage was observed in S.3/A3. Chlorophyll a, chl-b and carotenoids content in leaves decreased in each cultivar; however, the decrement was more brisk in S.3/A3. Proline, total soluble sugar, ascorbic acid and abscisic acid were elevated in TV-23 whereas hydrogen peroxide, superoxide anion, lipid peroxidation and electrolyte leakage increased rapidly in S.3/A3. Starch content decreased both in leaves and roots of each cultivar and was more pronounced in roots of TV-23. Under drought, enhanced activities of ascorbate peroxidase, catalase, peroxidase and superoxide dismutase were recorded in both roots and leaves of each cultivar, but the rate of enhancement was more in TV-23. This indicated that tolerant cultivar exhibited higher antioxidant capacity and a stronger protective mechanism such that their ultrastructural integrity was better maintained during exposure to drought stress. PMID- 26364465 TI - Mineralogy of agricultural soil of selected regions of South Western Karnataka, Peninsular India. AB - Agricultural soils of selected regions of Southwestern Karnataka, Peninsular India, were subjected to systematic mineralogical characterization along with the study of soil physical properties. Physical properties such as soil texture and micro porosity were studied using particle size analyses and positron annihilation lifetime analysis (PALS) technique, respectively. The latter was used to analyze micro porosity of agricultural soil. Both major and minor minerals were identified and confirmed by some analytical techniques like thin section study, powder X-ray diffraction, X-ray fluorescence spectroscopy and Fourier transform infrared spectroscopy. PMID- 26364466 TI - Dose and time dependent efficacy alteration of different defoliants on seed cotton yield. AB - Field experiments were conducted during 2012 and 2013 to determine the effect of select defoliants i.e dropp ultra and ethrel, their optimal dose and suitable time of application on earliness and seed cotton yield in 3 American cotton cultivars. MRC7361BGII (3055.2 kg ha(-1)) and MRC7017BGII (2913.0 kg ha(-1)) resulted in significantly improved seed cotton yield as compared to F1 861 (2346.0 kg ha(-1)). Dropp ultra? @ 200 ml ha(-1) revealed highest yield (3018.7 kg ha(-1)) followed by ethrel @ 2000 ppm (2820.1 kg ha(-1)) and control (2730.0 kg ha(-1)) , while statistically least yield (2516.9 kg ha(-1)) was observed with higher dose of dropp ultra @ 225 ml ha(-1). Defoliants applied 150 days after sowing (DAS) resulted in significantly better yield (2853.3 kg ha(-1)) as compared to the early application at 140 DAS (2689.5 kg ha(-1) owing to improvement in open bolls and boll weight. Pooled data indicated that dropp ultra @ 200 ml ha(-1) has potential to promote crop earliness, better boll opening and their retention by keeping vegetative and reproductive growth in harmony to enhance seed cotton yield. PMID- 26364467 TI - In vitro cytotoxicity study for electron beam cured adhesive tape for bio-medical application. AB - A device made for biomedical applications must be biocompatible and biologically safe for use. The used ingredients may leach off a device into adjacent tissue and can harm the body after or during application. In the present study qualitative and quantitative methods were used to assess the cytotoxicity of electron beam (e-beam) cured polyurethane pressure sensitive adhesive (PU-PSA) tape materials made for different biomedical applications. In the qualitative morphological results, it was found that there was no cell lysis or morphological changes in triplicate culture wells of the extract of e-beam cured PU-PSAtape. In the quantitative method of cytotoxicity studies, MTT cell viability (%) for PSA tape samples were >90, i.e., relative value of toxicity was nil. In case of agar overlay test for test samples, the relative value of toxicity was nil, while in filter diffusion score for the test samples was between 0-0.2, hence the relative degree of toxicity was nil. PMID- 26364468 TI - Response surface methodology for standardisation of lignocellulosic biomass saccharification efficiency of NSF-2 fungus isolate. AB - Lignocellulosic biomass can be used as a low cost substrate for cellulase production. In the present study an attempt was made to optimize physicochemical condition standardization for simultaneous cellulase production by NSF-2 fungal isolate, using wheat straw as a substrate and enzymatic hydrolysis of wheat straw by cellulase produced in-vitro by NSF-2 fungal isolate. Experiments showed maximum saccharification after 5th day of incubation. Optimum pH and temperature for saccharification were 5 and 30 degrees C respectively. Further optimization was carried out by response surface methodology using Box-Behnken design (BBD). BBD was designed with different combinations of three variables (peptone as nitrogen source, lignocellulosic biomass as substrate and Tween--80 as surfactant, each at three levels 1 g l(-1), 2 g l(-1), 3 g l(-1), 0.5 g l(-1), 2.5 g l(-1), 5 g l(-1) and (0.05%, 0.10%, 0.15%) respectively. The model computed for R2 value (99.55%) indicated that this was appropriate and could be useful in predicting the effect of the studied variables. Experimental results showed maximum saccharification at the middle concentration of peptone and substrate, i.e., 2 g l(-1) and 2.5 g l(-1) respectively. Surfactant did not show much significant result. PMID- 26364469 TI - Synthetic and biological studies on thioxoquinazolinone substituted isoxazoles. AB - Eighteen novel 5-phenyl-3-(substitutedthioxoquinazolinonyl) isoxazoles (5a-r) were synthesized by cycloaddition of various chalcones with hydroxylaminehydrochloride (NH2OH.HCl). All the newly synthesized compounds were confirmed by their spectral and analytical data. They were evaluated for antimicrobial, antihelminthic, analgesic and anti-inflammatory activities with an objective to evaluate the effect of thioxoquinazolinone substituted isoxazoles. Compounds 5a, 5f, 5g, 5k and 51 showed significant antimicrobial, anthelmintic, analgesic and anti-inflammatory activities. Further, isoxazoles having bromo substituted thioxoquinazolinones exhibited excellent activities than iodo substituted thioxoquinazolinones. PMID- 26364470 TI - Evaluation-of soil enzyme activities as soil quality indicators in sludge-amended soils. AB - Soil enzymatic activities are commonly used as biomarkers of soil quality. Several organic and inorganic compounds found in municipal wastewater sludges can possibly be used as fertilizers. Monitoring and evaluating the quality of sludge amended soils with enzyme activities accepted as a beneficial practice with respect to sustainable soil management. In the present study, variation of some enzyme activities (Alkaline phosphatase, dehydrogenase, urease and beta glucosidase activities) in soils amended with municipal wastewater sludge at different application rates (50, 100 and 200 t ha(-1) dry sludge) was evaluated. Air dried sludge samples were applied to soil pots and sludge-soil mixtures were incubated during a period of three months at 28 degrees C. The results of the study showed that municipal wastewater sludge amendment apparently increased urease, dehydrogenase, alkaline phosphatase and P-glucosidase activities in soil by 48-70%, 14-47%, 33-66% and 9-14%, respectively. The maximum activity was generally observed in sludge amended soil with dose of 200 t ha(-1). Urease activity appeared to be a better indicator of soil enhancement with wastewater sludge, as its activity was more strongly increased by sludge amendment. Accordingly, urease activity is suggested to be soil quality indicator best suited for measuring existing conditions and potential changes in sludge-amended soil. PMID- 26364471 TI - Maturation profile and fecundity of the exotic Oreochromis niloticus in the River Yamuna, India. AB - The knowledge on the reproductive biology of fish Oreochromis niloticus (Linnaeus, 1758) in riverine condition is meagre in the Indian sub-continent which is necessary for the development of an appropriate fishery management protocols for the rivers. In this context, the gonadal maturation profile and fecundity of 0. niloticus was studied. Mature, spawning and spent females recorded in almost all the months of the year evidenced multiple and prolonged breeding behaviour. An overall sex ratio (M/F) of 1: 1.08 observed was statistically non-significant from expected 1:1 ratio (chi2=6.994219, p=0.8642) indicating that males and females were statistically equal in number. The absolute fecundity ranged from 1192 to 4760 with mean of 2590 eggs from ovary weighing between 1.91 g to 28.89 g. Monthly changes in gonado-somatic index (GSI) revealed that fish bred throughout the year except in July and August, but at peak between October-November and March-June. Size at first maturity of male was estimated as 229.6 mm with confidence limit of 235.9 and 223.6 mm and for female as 238.1 mm with confidence limit of 244.7 and 231.7 mm, respectively. PMID- 26364472 TI - Studies on characterization and removal of methylene blue with Delonix regia plant litters activated carbon encapsulated nano metal oxide. AB - An advanced adsorbent material prepared by encapsulating nano-metaloxide on an activated carbon of Delonix regia plant litters was tested for its efficiency and superiority as an improved, advanced activated carbon material. It was subjected to modern instrumental techniques to evolve its morphology and its structure by FTIR, SEM, TEM, XRD, EDAX and BET studies. The size of MgO particles was in the range of 20 nm-25 nm. The surface area of nano composite was 632 m2 g(-1). Experimental results, based on batch mode of experiments, indicated that the adsorbent could remove 90% dye for the adsorbent dosage of 100 mg, at pH 7.0 and contact time of 120 min. The adsorption equilibrium data were well correlated for both, Langmuir and Freundlich isotherms. The monolayer adsorption capacity Qo was found to be 14.425 mg g(-1) for the composite. The kinetic adsorption data fitted the pseudo first order modeled by Lagergren and also intra particle diffusion. Removal efficiency of the composite adsorbent was higher than the uncoated adsorbents. Regeneration of exhausted adsorbent showed considerable improved variation in comparison to normal activated carbon materials. PMID- 26364473 TI - Association of growth related seedling traits in Acacia senegal under arid environment of western Rajasthan. AB - Climatic models and predictions indicate increase in aridity world over due to global warming. Arid environments occupy about one third land area of the world. A. senegal is the most important dryland resource of western Rajasthan desert ecosystem. The seeds of 13 low and high seed yielding exotic and indigenous provenances were evaluated for diversity and interrelationship among growth related seedling traits targeting establishment and end use of this species. Under the present study most of the growth related seedling traits varied within and amongst provenances. Highly significant correlation of dry biomass per plant of more than 72% with root length (73.3%), collar diameter (72.2%), shoot dryweight (99.7%), root dry weight (95.7%) and seedling length (79.9%) under the present study may be used for early selection. Similarly, highly significant positive correlation of seedling length with seven out of 12 growth related seedling traits validate strong inherent association of these traits under strong genetic control and are amenable for selection. Significant negative correlation in number of nodules per plant with root/shoot length ratio (-57.6%) and no correlation with 10 out of 12 growth related seedling traits tested advocate emphasis on other growth related seedling traits in selection of elite A. senegal genotypes for afforestation. The non significant associations suggest that per cent germination was independent of other characters and could be selected separately. PMID- 26364474 TI - Influence of culture conditions on production of phytase by Zygosaccharomyces baili var. balil. AB - Microbial phytases are phosphohydrolytic enzymes which are gaining attention for their commercial exploitation in feed and food industry. In the present study, ten yeasts were isolated from different soil samples and screened for their phytase producing capability. Among these isolates, the most promising yeast strain was Zygosaccharomyces bailii var. bailii which produced highest phytase yield (6.36 U ml(-1)) in malt yeast extract glucose peptone (MYGP) medium. In order to improve phytase production by Zygosaccharomyces bailii, different physio chemical parameters were optimized. The optimal conditions for phytase production was found to be: incubation time-42 hr, temperature-30 degrees C, medium pH-6.0 and substrate (calcium phytate) concentration-0.1%. Glucose at 0.5% concentration supported higher phytase production (13.75 U ml(-1)) than other carbon sources tested. Metal ions (Ca+/+, Na+, K+, Mg++) and additives; ethylene diamine tetraacetate (EDTA), sodium dodecyl sulphate (SDS) and toluene did not affect enzyme production. However, Zn++, Ni++, Ba++, Pb++ and detergents like Triton X 100 and Tweens strongly inhibited (>90%) phytase production. An overall 2.21-fold enhancement in phytase activity (6.36-->14.03 U ml(-1)) was attained after optimization studies. PMID- 26364475 TI - Real time PCR expression analysis of gene encoding p5cs enzyme and proline metabolism under NaCI salinity in rice. AB - Regulation of proline accumulation in seedlings of rice (Oryza sativa L. cv. Lunishree) was investigated. The increasing concentration of NaCl from 85 mM to 425 mM NaCl progressively increased proline content in rice. The maximum increase in proline content was recorded at 425 mM NaCl concentration as compared to control and other concentrations of NaCl. The highest significant activity of proline synthesizing enzymes, delta1-Pyrrolline-5-carboxylate synthetase, delta1 Pyrrolline-5-carboxylate reductase and Ornithine-delta- aminotransferase with lowest activity of proline hydrolysis enzymes;Proline dehydrogenase was also recorded at 425 mM NaCl salinity over control and other concentrations of NaCI with insignificant increase in the activity of delta1-Pyrrolline-5-carboxylate synthetase and Ornithine-delta-aminotransferase at 85 mM NaCI over control. It was found that the transcript of gene encoded with p5cs is up regulated about 1.35 folds under salinity stress. This gene synthesis an osmo protectant to help the plant resist the change in osmotic imbalances. Externally addition of MnCl2 at 300 mg/220 ml 1/2 strength Hoagland solution, having 1% NaCI, was also seen to increase 893.9% proline content of this variety as compared to control. PMID- 26364476 TI - Comparison of pathogenicity of Alternaria pellucida and Curvularia lunata on weed Echinochloa species. AB - Echinochloa spp. are the most important weeds in rice fields. In this research Curvularia lunata and Alternaria pellucida were isolated from these weeds and their pathogenicity effects were compared on these weeds and five rice cultivars in a completely random design with three replications in greenhouse conditions. Fungi were inoculated on weeds and rice cultivars, using spore suspension consisting of 10' spore ml(-1) of distilled water. Results indicated significant effect of Curvularia lunata and Alternaria pellucida on Echinochloa oryzicola and E. crus-galli. In the present study, effect of C. lunata on fresh weight, dry weight and height of Echinochloa species based on variance analysis table, a significant reaction was observed for height and fresh weight, but for dry weight reaction was not significant. The effect of A. pellucida on fresh weight, dry weight and height of Echinochloa species based on variance analysis table, a significant reaction was observed for all the three traits. Also, rice cultivars did not show any significant reaction to C. lunata and A. pellucida. The results showed that in comparison between effect of Curvularia lunata and Alternaria pellucida on Echinochloa spp., disease rating caused by A. pellucida on E. oryzicola and E. crusalli was more than disease rating caused by C. lunata and these species of weed were more susceptible to A. pellucida. However, A. alternata can be considered as a better promising bioherbicide to control Echinochloa spp. PMID- 26364477 TI - Impact of Makowal type water system on crop productivity in Shivalik foothills of India. AB - The availability of water through community based water harvesting structure has intensified agriculture and improved livelihood of the surveyed beneficiary households in the Shivalik foothills of India. Before the introduction of Makowal Type Water Harvesting System (before MTWHS), only 83.8% farmers in kharif and 79.7% during rabi season were growing crops but after its introduction (after MTWHS) the corresponding values improved to 100% and 97.3%, respectively, thus increasing cropping intensity from 145% to 189%. Introduction of MTWHS enabled farmers to take paddy and agro-forestry during Kharif, and vegetables and fodder during Rabi season. The increase in cultivated area due to MTWHS was to the tune of 46.1% in Kharif and 36.3% during Rabi, while increase in crop productivity ranged from 55.1% to 111.3% in kharif and 8.6 to 132.0% in Rabiseason. Better availability of irrigation changed varietal spectrum in favour of hybrids and high yielding varieties and farmers started adopting improved agronomic practices targeting better input-use efficiency. The MTWHS produced positive impact on the on-farm (crops, dairy and agro-forestry) sources of income and reduced the relative dependence on off-farm activities (labour, community forest area, etc.) for earnings. This system has brought drinking water very close to hutments of rural women thus reducing their drudgery and saving time. In general, rainwater harvesting from forest watersheds has resulted in quantum jumps in crop and milk production and acted as a catalyst to tie up the economic interest of communities, along with forest protection. PMID- 26364478 TI - Release of zinc and cadmium from sludge amended soil as influenced by varying levels of moisture and temperature. AB - Limited information is available related to the effect of moisture and temperature on release of metals from sludge treated soils. In an incubation experiment, effect of ten levels of sludge (0, 1.12, 2.24, 4.48, 8.96, 17.9, 35.8, 71.6, 142, 285 g kg(-1)), two levels of moisture (field capacity and 2.5 cm standing water) and two levels of temperature (20 and 35 degrees C) on the release of zinc and cadmium was evaluated in acid and alkaline soils. The results indicated that application of sludge was more effective in enhancing EDTA extractable Zn and Cd in acid soil than in alkaline soil. On an average, maximum increase in release of EDTA extractable Zn and Cd were 32.0 and 5.2 fold in sludge treated soil over control. There was decrease in EDTA extractable Zn and Cd by 37.7% and 25.4%, respectively under submergence as compared to that under field capacity. On an average, the amount of EDTA extractable Zn and Cd increased by 22.6% and 43.6%, respectively at 35 degrees C than that at 20 degrees C. PMID- 26364479 TI - Assessment of genetic diversity in quality protein maize(QPM) inbreds using ISSR markers. AB - Genetic diversity of 49 maize inbreds was assessed using twelve ISSR primers. A wide variation in PCR products was revealed in terms of size (280 to 3000 bp), extent of polymorphism (94.87%) and number of bands (4-9). As a whole, 78 ISSR bands were produced (including four monomorphic bands) with an average of 6.5 bands per primer and the maximum number of bands (9) being produced by primer OUAT-8. Five ISSR primers (OUAT-8, OUAT-9, OUAT-15, OUAT 17 and OUAT-18) revealed higher PIC value (around 0.70) along with 100% polymorphism indicating better allelic diversity. While, ISSR primer OUAT-15 revealed higher number of polymorphic bands (8) with 100% polymorphism as well as considerably high PIC and Rp values. Thus, such an informative and discriminative primer is of immense value for the study of genetic diversity in a set of maize genotypes. The similarity index values ranged from 0.3 to 0.9 with an average of 0.522 and BQPM 1-14 maintained the highest genetic distance as revealed from its lowest average similarity coefficient value (0.393) with rest of the genotypes. BQPM 1-14, BQPM 1-8, BQPM 3-10, BQPM 6-8 and B 1110-7-2 were identified to be highly divergent among the test inbreds which could be sorted out as valuable materials for heterosis breeding for production of single cross hybrids. PMID- 26364480 TI - Efficacy evaluation of selected herbicides on weed control and productivity evaluation of Bt cotton in Punjab. AB - Field experiments were conducted during Kharif 2012 and 2013 to evaluate the efficacy of different herbicides for weed management in cotton. Highest seed cotton yield (3537.3 kg ha(-1)) was recorded in weed free plots followed by pendimethalin @1.0 kg a.i ha(-1) as Pre.em.+quizalofopethyl @50 g a.i ha(-1) post em at 2-4 weed leaf stage + one hoeing (3318.9 kg ha") owing to improved number of bolls per plant and boll weight. Statistically least yield was recorded underweedy check (1435.4 kg ha(-1)). Application of pyrithiobac sodium could not express any visible toxic effect on crop indicating its selectivity for cotton, although none of the tested new chemicals i.e., pyrithiobac sodium@ 62.5g a.i ha( 1) and quizalofopethyl @50g a.i ha(-1) when applied alone could not outperform the existing recommended chemicals for weed management. Yield losses to the extent of 6.2-59.4% were recorded due to weed competition. Weed control efficiency (WCE) was highest under weed free check (86.8%) followed by pendimethalin @1.0 kg a.i ha(-1) as Pre. em.+quizalofopethyl @50g a.i ha(-1), at 2-4 weed leaf stage + one hoeing (73.7%), whereas minimum values were for weedy check (24.7%). Though net returns (r94660 ha(-1)) were highest for weed free check but higher B:C ratio (2:11) was observed for pendimethalin @1.0 kg a.i ha( 1) as Pre em.+quizalofopethyl @50 g a.i ha(-1) post-em at 2-4 weed leaf stage+one hoeing. Therefore, for reasons such as labor shortage besides their timely availability, using these herbicides in combination with cultural practices could be the practical solution foreconomically efficient and effective weed management. PMID- 26364481 TI - Characterization of rice (Oryza sativa L.) genotypes on the basis of morpho physiological and biochemical traits grown under aerobic situation in rainfed ecosystem . AB - The objective of the present study was to examine the effect of aerobic situation on yield, physiological and biochemical traits of advanced breeding lines of rice. Experiment was conducted with two set of rice genotypes under two water regimes (aerobic and irrigated), during three consecutive wet seasons 2010-2012. Significant decrease in yield was observed in rice genotypes grown under aerobic situation as compared to the irrigated ones. Promising rice genotypes having the ability to maintain high plant biomass, harvest index, early vegetative vigour, improved physiological and biochemical traits in terms of relative water content (RWC), leaf area index (LAI), total soluble sugar, starch, protien and proline content help to sustain higher grain yield under aerobic situation. The yield gap between aerobic and irrigated rice ranged between 24% to 68%. Grain yield showed positive correlation with harvest index (0.434), test weight (0.647), plant biomass (0.411) and effective tiller numbers (0.473), whereas spikelet sterility was negative associated (-0.380). The current study suggested that promising genotypes viz., IR77298-14-1-2-130-2, IR84899-B-182-3-1-1-2, IR84887-B-157-38-1-1 3 and IR 84899-B-179-1-1-1-2 for aerobic situation, showing yield advantage due to better performance of physiological and biochemical traits, might be adopted in large area of rainfed ecosystem as well as in irrigated areas where water scarcity was a major problem. PMID- 26364482 TI - Fuel wood properties of some oak tree species of Manipur, India. AB - Five indigenous oak tree species, i.e., Castanopsis indica (Roxb. ex Lindl.) A.DC., Lithocarpus fenestratus (Roxb.) Rehder, Lithocarpus pachyphyllus (Kurz) Rehder, Lithocarpus polystachyus (Wall. ex A.DC.) Rehder and Quercus serrata Murray were estimated for their wood properties such as calorific value, density, moisture content and ash content from a sub-tropical forest of Haraothel hill, Senapati District, Manipur. Wood biomass components were found to have higher calorific value (kJ g(-)) than bark components. The calorific values for tree species were found highest in L. pachyphyllus (17.99 kJ g(-1)) followed by C. indica (17.98 kJ g1), L. fenestratus (17.96 kJ g"), L. polystachyus (17.80 kJ g( 1)) and Q. serrata (17.49 kJ g(-1)). Calorific values for bole bark, bole wood and branch bark were found significantly different (F > 3.48 at p = 0.05) in five oak tree species. Percentage of ash on dry weight basis was found to be highest in Q. serrata (4.73%) and lowest in C. indica (2.19%). Ash content of tree components gives a singnificant factor in determining fuelwood value index (FVI). Of all the five oak tree species, Q. serrata exhibited highest value of wood density (0.78 g cm-) and lowest was observed in C. indica (0.63 g cm(-3)). There was significant correlation between wood density (p<0.05), ash content (p<0.01) with calorific value in oak tree species. Fuelwood value index (FVI) was in the following order: C. indica (1109.70) > L. pachyphyllus (898.41)> L. polystachyus (879.02)> L. fenestratus (824.61)> Q. serrata (792.50). Thus, the present study suggests that C. indica may be considered as a fuelwood oak tree species in Manipur. PMID- 26364483 TI - Molecular analysis of soybean varying in water use efficiency using SSRs markers. AB - A set of 91 soybean germplasm lines, collected from different parts of the world, were screened for Water Use Efficiency (WUE) using Carbon Isotope Discrimination (CID) technique and were characterized for 10 quantitative traits. After screening under field condition, 44 soybean genotypes showed variations in WUE. Molecular diversity of these 44 diverse soybean lines was carried out with 26 Simple Sequence Repeats (SSRs) markers, of which 10 were polymorphic (38.47% polymorphism). 28 alleles were observed which were distributed over 10 loci, with an average of 2.8 alleles per locus. Polymorphism Information Content (PIC) value of 10 polymorphic markers ranged from 0.40 (locus Satt460) to 0.67 (locus satt260), with an average of 0.46. Pair-wise genetic similarity value, as calculated by simple matching coefficient, ranged from 0.99 to 0.40, with an average of 0.70. Genotypes were clustered using NTSYS-pc software employing unweighted paired group method using arithmetic averages to generate the dendrogram. Dendrogram exhibited 8 distinct clusters with a similarity coefficient of 0.69. Genotypes having low to medium and medium to high CID value were clustered in distant groups indicating usefulness of these polymorphic SSRs markers for differentiating genotypes on the basis of their CID value. The findings of this study indicate the need for broadening genetic base of the present Indian soybean cultivars through use of exotic sources of variation towards WUE. Thus, diverse genotypes identified in this study would be beneficial to soybean breeders to develop mapping population to identify QTLs for WUE. PMID- 26364484 TI - CO2 emission of coal spontaneous combustion and its relation with coal microstructure, China. AB - Coal spontaneous combustion is widely distributed all over the world. CO2 is the main greenhouse gas emitted by coal spontaneous combustion. In the present study characters of CO2 emitted by 10 typical Chinese coal spontaneous combustion and the influence of raw coal functional group on CO2 was studied. CO2 already exists under normal temperature as coal exposed in atmosphere. Under low temperature, the quality of CO2 released by coal spontaneous combustion is relatively small, but tends to increase. And corresponding with it, the oxygen consumption amount is also small. At medium temperature, the oxygen consumption increases rapidly and CO2 mass release rate begins to increase rapidly. Then, CO2 release rate increase rapidly under relatively high temperature (higher than 673 K). Over 873K, concentration of O2 is 6% and release rate of CO2 tends to be steady. It also concluded that mass ratio of CO to CO2 (CO/CO2) during coal spontaneous combustion was lowerthan 0.10 at low temperature. And then, it increased rapidly at medium temperature and reached to top at about 673 K. At 673-873 K, the ratio decreased again, and did not decrease evidently at about 873K. At temperature higher than 873K, the ratio was about 0.13. During the whole testing temperature range, CO/CO2 was not be higher than 0.26, lower than 0.2. This means that release rate of CO2 was much higher than CO during the whole process of coal spontaneous combustion. Moreover, the gas release quantity of CO2 is positively related with carbony content in raw coal. Carbonyl and carboxyl were both material basis of CO2. PMID- 26364485 TI - The effect of organic loading rate on VFA/COD ratio for methane production from an EGSB reactor. AB - The present study evaluated the effect of organic loading rate (OLR) on VFA/COD ratio for continuous production of methane using an expanded granular sludge bed(EGSB) reactor for 200 d. Reactor performances were studied in treating high OLRs ranging from 4.91 +/- 0.54 to 16.79 +/- 1.62 g-COD l(-1)d(-1) of glucose based synthetic wastewater in a mesophilic condition. Results showed that performance of anaerobic fermentation system was distinctly influenced by OLR in terms of organic removal efficiency, VFA yield, methane production rate and system stability.Acetic and propionic acids accounted for 80-90% of total VFA, and presented highest VFA concentration and composition of VFA showed minor changes with OLR variation. Moreover, an increase in OLR increased VFA/COD ratio in the whole operation period and high VFA/COD ratio could inhibit methanogenesis at high OLR (16.79 +/- 1.62 g-COD l(-1) d(-1)). PMID- 26364486 TI - Dentists deserve transparency from insurance carriers. PMID- 26364487 TI - A view from the midway. PMID- 26364488 TI - Connecting the dots between CHRONIC DISEASE and oral health. PMID- 26364489 TI - The FUTURE of DENTISTRY. PMID- 26364490 TI - Advice for working with an attorney. PMID- 26364491 TI - Like sailing, philanthropy offers perspective. PMID- 26364493 TI - See what Sam Wexler has been collecting. PMID- 26364492 TI - Advocates work to gain a seat at the table of policymakers. PMID- 26364494 TI - What practice model is right for you? PMID- 26364495 TI - Ophthalmic Nursing: More Than Meets the Eye. PMID- 26364496 TI - Welcome Summer. PMID- 26364497 TI - Glaucoma Medications Update: How to Improve Compliance and Adherence. PMID- 26364498 TI - Iris Heterochromia. PMID- 26364499 TI - Understanding Informed Consent. PMID- 26364500 TI - Age-Related Macular Degeneration (AMD) Agents. . PMID- 26364501 TI - Barbara Sanchez, RN, MSN. PMID- 26364502 TI - Geraniol attenuates 2-acetylaminofluorene induced oxidative stress, inflammation and apoptosis in the liver of wistar rats. AB - 2-Acetylaminofluorene (2-AAF), is a well-known liver toxicant, generally used to induce tumors in laboratory animals. Geraniol (GE), a monoterpene found in essential oils of herbs and fruits, has been known to possess preventive efficacy against chemically induced toxicities. The present study was designed to analyze the protective effect of GE against 2-AAF induced oxidative stress, inflammation, hyperproliferation and apoptotic tissue damage in the liver of female Wistar rats. 2-AAF (0.02% w/w in diet) was administered and subjected to partial hepatectomy, as a mitogenic stimulus for the induction of hyperproliferation of liver tissue. GE was pre-treated orally at two different doses (100 and 200 mg/kg b.wt.) dissolved in corn oil. GE pre-treatment significantly ameliorated 2-AAF induced oxidative damage by diminishing tissue lipid peroxidation accompanied by the increase in enzymatic activities of catalase, glutathione peroxidase, glutathione reductase, superoxide dismutase and reduced glutathione content. The level of serum toxicity markers (AST, ALT, LDH) was found to be decreased. Pre treatment with GE downregulated the expression of caspase-3,9, COX-2, NFkB, PCNA, iNOS, VEGF and significantly decreased disintegration of DNA. Histological findings further revealed that GE significantly restores the architecture of liver tissue. In the light of the above observations it may be concluded that GE may be used as preventive agent against 2-AAF induced oxidative stress, inflammation, hyperproliferation and apoptotic damage. PMID- 26364503 TI - Incidence and risk factors for community-associated methicillin-resistant Staphylococcus aureus in New York City, 2006-2012. AB - This study aims to describe changes in incidence and risk factors for community associated methicillin resistant Staphylococcus aureus (CA-MRSA) infections upon admission to two New York City hospitals from 2006 to 2012. We examined the first hospitalization for adult patients using electronic health record and administrative data and determined the annual incidence/1000 admissions of total S. aureus, total MRSA, and CA-MRSA (within 48 h of admission) in clinical specimens over the study period. Logistic regression was used to identify factors associated with CA-MRSA in 2006 and 2012. In 137 350 admissions, the incidence of S. aureus, MRSA, and CA-MRSA/1000 admissions were 15.6, 7.0, and 3.5, respectively. The total S. aureus and MRSA isolations decreased significantly over the study period (27% and 25%, respectively) while CA-MRSA incidence was unchanged. CA-MRSA increased as a proportion of all MRSA between 2006 (46%) and 2012 (62%), and was most frequently isolated from respiratory (1.5/1000) and blood (0.7/1000) cultures. Logistic regression analysis of factors associated with isolation of CA-MRSA showed that age ?65 years [odds ratio (OR) 2.3, 95% confidence interval (CI) 1.2-4.5], male gender (OR 1.8, 95% CI 1.2-2.8) and history of renal failure (OR 2.6, 95% CI 1.6-4.2) were significant predictors of infection in 2006. No predictors were identified in 2012. PMID- 26364504 TI - A freeze-dried kit formulation for the preparation of Lys(27)(99mTc-EDDA/HYNIC) Exendin(9-39)/99mTc-EDDA/HYNIC-Tyr3-Octreotide to detect benign and malignant insulinomas. AB - About 90% of insulinomas are benign and 5%-15% are malignant. Benign insulinomas express the glucagon-like peptide-1 receptor (GLP-1R) and low levels of somatostatin receptors (SSTR), while malignant insulinomas over-express SSTR or GLP-1R in low levels. A kit for the preparation of Lys(27)((99m)Tc-EDDA/HYNIC) Exendin(9-39)/(99m)Tc-EDDA/HYNIC-Tyr(3)Octreotide was formulated to detect 100% of insulinomas. The formulation showed radiochemical purity of 97+/-1%, high stability in human serum, and GLP-1R and SSTR affinity. The biodistribution and imaging studies demonstrated properties suitable for its use as a target-specific agent for the simultaneous molecular imaging of GRP-1R- and/or SSTR-positive tumors. PMID- 26364505 TI - Modulatory Effects of Curcumin and Tyrphostins (AG494 and AG1478) on Growth Regulation and Viability of LN229 Human Brain Cancer Cells. AB - In this study we employed curcumin as a potent adjuvant agent in the treatment of human brain cancer involving selective EGFR kinase inhibitors: tyrphostins AG494 and AG1478. Aim of this work was to evaluate the effect of tested compounds on autocrine growth, cell cycle, and viability of LN229 cells, as well as to assess their proapoptotic and genotoxic properties. Our results showed that all tested compounds significantly inhibited autocrine growth of the investigated cell line in a dose dependent manner. However they are characterized by different kinetics of cell growth inhibition. Suppression of growth by the tyrphostins was completely or partially reversible in contrast to curcumin. Curcumin increased the cytostatic and/or cytotoxic potential of AG494 and AG1478. Tyrphostins did not have genotoxic properties regardless of concentration used, whereas curcumin cytotoxic and genotoxic properties were directly proportional to the concentration. Curcumin significantly increased tyrphostins cytotoxicity. The most promising of the obtained results may be the use of curcumin and tyrphostin AG494 in the treatment of cancer cells. Anticancer effect of the mixture was confirmed by increase of cytotoxic effect, decrease of viability, stimulation of apoptotic procesess, irreversible DNA damage, and decrease of the ROS in the culture of glioblastoma cells. PMID- 26364507 TI - Immunotherapies currently in development for the treatment of type 1 diabetes. AB - INTRODUCTION: Type I diabetes (T1DM) is an autoimmune disorder that affects the pancreas' ability to produce insulin. While T1DM can be managed using insulin therapy, patients face financial burden, serious complications and premature mortality, from the disease. Efforts have sought to define and ultimately suppress the underlying autoimmune attack that results in T1DM. AREAS COVERED: The authors lay out promising immunosuppressive and immunomodulating drugs currently in development for T1DM and outline options for future immune treatment for the disorder. There have been several pharmacological strategies to combat the immune attack which will serve as the organization for this review: antigen specific therapies; monoclonal antibodies; fusion proteins; alternate Treg affectors. EXPERT OPINION: Immunosuppression and immunomodulation studies in T1DM demonstrated differing levels of slowing the progression of the immune attack; however, no single therapeutic approach provides a lasting halt of the immune attack and remission of the disease. The immunosuppressants (teplizumab, rituximab and abatacept) show promise in slowing the T1DM progressions for a specific subpopulation of T1DM patients, but this approach appears temporary and has the potential for unwanted side affects. Combination therapies may have the greatest chance of achieving durable cessation of the T1DM autoimmune attack. PMID- 26364508 TI - An evaluation of RVX-208 for the treatment of atherosclerosis. AB - INTRODUCTION: RVX-208 is a first-in-class, orally active, novel small molecule in development by Resverlogix Corporation (Calgary, AB, Canada). It acts through an epigenetic mechanism by inhibiting the bromodomain and extraterminal (BET) family of proteins, increasing apolipoprotein A-I (apoA-I) and targeting high-density lipoprotein (HDL) metabolism, including generating of nascent HDL and increased larger HDL particles, resulting in the stimulation of reverse cholesterol transport. RVX-208 also has a beneficial effect on inflammatory factors known to be involved in atherosclerosis and plaque stability. New therapeutic strategies are needed for patients with atherosclerosis. AREAS COVERED: In this review, the authors evaluate the use of RVX-208 as an agent for the treatment of atherosclerosis. The article is based on a literature search considering both animal and human studies available on PubMed as well as Media Releases from the Resverlogix Corporation. EXPERT OPINION: The current evidence suggests promising beneficial effects of this novel drug in the prevention and treatment of atherosclerosis and other metabolic disorders. Its unique mechanism of action is encouraging; it affects several pathways and has a modest effect on HDL levels. There is also a shift in particle size to larger HDL particles, which may have potent atheroprotective effects. Future clinical development is needed, including safety assessment. PMID- 26364509 TI - Magnetic Assembly and Cross-Linking of Nanoparticles for Releasable Magnetic Microstructures. AB - This article describes a versatile method to fabricate magnetic microstructures with complex two-dimensional geometric shapes using magnetically assembled iron oxide (Fe3O4) and cobalt ferrite (CoFe2O4) nanoparticles. Magnetic pole patterns are imprinted into magnetizable media, onto which magnetic nanoparticles are assembled from a colloidal suspension into defined shapes via the shaped magnetic field gradients. The kinetics of this assembly process are studied by evaluation of the microstructure features (e.g., line width and height) as a function of time, particle type, and volume fraction. After assembly, the iron oxide particles are cross-linked in situ and subsequently released by dissolving a sacrificial layer. The free-floating magnetic structures are shown to retain their patterned shape during manipulation with external magnetic fields. PMID- 26364510 TI - Clinical and Sociodemographic Factors Associated with Cognitive Impairment and Neuroprotection in Diabetes Patients. AB - The aim of this study is to analyze the potential impact of factors (clinical and demographic variables and comorbidities) associated with Diabetes Mellitus (DM) on certain mental processes related to cognitive impairment, with special attention to the analysis of parameters that define processing speed and executive function. Neuropsychological examination of elderly Spanish patients (N = 59, 33 females, M age 70.98 years) diagnosed with DM, in addition to application of an ad hoc questionnaire to collect information on comorbidities and other relevant demographic variables. Based on a cross-sectional design, correlational analysis was carried out. Cognitive performance showed an inverse relationship to age and cardiopathology while years of schooling and regular physical activity appeared as neuroprotective factors. DM is an illness which, linked to other variables, can be regarded as a risk factor for the development of cognitive impairment. Certain factors (physical activity and cognitive stimulation) have the potential to mitigate this tendency. There is a need to further our understanding of the neurobiological mechanisms involved. PMID- 26364511 TI - Potential biomarkers associated with diabetic glomerulopathy through proteomics. AB - Diabetic nephropathy (DN) is characterized by the development of progressive glomerulosclerotic lesions gradually leading to an increasing loss of functioning kidney parenchyma. Relatively little proteomic research of isolated glomeruli of experimental animal models has been done so far. Isolated glomerular proteomics is an innovative tool that potentially detects simultaneous expressions of glomeruli in diabetic pathological contexts. We compared the isolated glomerular profiles of rats with and without diabetes. The proteins in the aliquots of glomeruli were subjected to two-dimensional gel electrophoresis. The protein spots were matched and quantified using an imaging analysis system. The peptide mass fingerprints were identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry and a bioinformation search. We found that diabetes increased collagen type I and collagen type IV levels in diabetic glomeruli when compared to normal control group using Dynabeads. We found that rats with diabetes had significantly higher abundance of the Protein disulfide isomerase associated 3, Aspartoacylase-3,3-hydroxymethyl-3-methylglutaryl Coenzyme A lyase, Lactamase beta 2 and Agmat protein. However, diabetic glomeruli in rats had significantly lower levels of the Regucalcin, rCG52140, Aldo-keto reductase family 1, Peroxiredoxin 1, and l-arginine: glycine amidinotransferase. These proteins of interest were reported to modulate disturbances in the homeostasis of endoplasmic reticulum stress, disturbance of inflammatory and fibrinogenic activities, impairing endothelial function, and dysregulation in the antioxidation capacity/oxidative stress in several tissue types under pathological contexts. Taken together, our high-throughput isolated glomerular proteomic findings indicated that multiple pathological reactions presumably occurred in DN. PMID- 26364512 TI - Characteristics and international comparability of the Finnish matrix sentence test in cochlear implant recipients. AB - OBJECTIVES: The first Finnish sentence-based speech test in noise--the Finnish matrix sentence test--was recently developed. The aim of this study was to determine the characteristics of the new test with respect to test-retest reliability, speech recognition curve, and international comparability in Finnish cochlear implant (CI) recipients. DESIGN: The speech reception thresholds (SRT) were measured by means of an adaptive test procedure and compared with the results of the traditional Finnish word test. Additional measurements for concurrent slope and SRT estimation were conducted to determine the speech recognition curve and to check the test-retest reliability. STUDY SAMPLE: The measurements were performed on 78 Finnish CI recipients. In a subset of 25 patients, additional measurements for test-retest reliability and slope determination were performed. RESULTS: The mean SRT was -3.5 +/- 1.7 dB SNR, with only a weak correlation with the Finnish word test. Test-retest reliability was within +/- 1 dB and the mean slope of the speech recognition curve was 14.6 +/- 3.6 %/dB. The rehabilitation results were similar to the results published for the German matrix test. CONCLUSIONS: The Finnish matrix test was found to be suitable and efficient in CI recipients with similar characteristics as the German matrix test. PMID- 26364513 TI - Case series of multiple repeat caesarean sections: operative, maternal, and neonatal outcome. AB - OBJECTIVE: The objective of this study is to review the maternal and neonatal morbidity and mortality associated with six or more caesarean section (CS). METHODS: We conducted a retrospective chart review, at King Abdulaziz University Hospital (KAUH) in Jeddah, for all patients admitted between 2000 through 2010 and identified five patients having more than six CS deliveries. RESULTS: Deliveries occurred in the ranges of 31-38 weeks, from which four cases required emergency CS. There were two cases in the series with a placenta previa. There was a single case of uterine dehiscence. Only one case required a blood transfusion and was complicated with a placenta accreta, bladder injury, urinary tract infection, and prolonged maternal hospital stay with neonatal intensive care unit (NICU) admission. All cases had moderate to severe adhesion intra operatively. Operative time was long in all cases with a range 55-106 min. One of the five cases had a postoperative wound infection. Finally, none of the current series showed fetal or maternal mortalities. CONCLUSIONS: The long-term complications associated with CS should be discussed with patients in the first and subsequent pregnancies. This case series highlighted the outcomes in these unique cases of higher order caesareans. PMID- 26364514 TI - Ghrelin ameliorates impaired angiogenesis of ischemic myocardium through GHSR1a mediated AMPK/eNOS signal pathway in diabetic rats. AB - OBJECTIVES: Ghrelin, an endogenous ligand of the growth hormone secretagogue receptor (GHSR), has been found to stimulate angiogenesis in vivo and in vitro. However, the effect and the corresponding mechanisms of ghrelin on impaired myocardial angiogenesis in diabetic and myocardial infarction (MI) rat model are still unknown. METHODS: In the present study, adult SD rats were randomly divided into 4 groups: control, DM, DM+ghrelin, DM+ghrelin+[D-Lys3]-GHRP-6 groups. DM was induced by streptozotocin (STZ) 60 mg/kg body weight. 12 weeks post STZ injection all groups were subjected to MI, which was induced by ligation left anterior descending artery (LAD). Ghrelin and [D-Lys3]-GHRP-6 were administered via intraperitoneal injection at the doses 200 MUg/kg and 50mg/kg for 4 weeks, respectively. Left ventricular function, microvascular density (MVD), myocardial infarct size, the expression of hypoxia-inducible factor (HIF1alpha), vascular endothelial growth factor (VEGF), fetal liver kinase-1 (Flk-1) and fms-like tyrosine kinase-1 (Flt-1), AMPK and endothelial nitric oxide synthase (eNOS) phosphorylation were examined. RESULTS: Compared with the DM group, left ventricular ejection fraction (LVEF), fractional shortening (FS), and MVD were increased, whereas myocardial infarct size decreased remarkably in DM+ghrelin group. For the mechanism study, we found that ghrelin promoted the HIF1alpha, VEGF, Flk-1 and Flt-1 expression, AMPK and eNOS phosphorylation in diabetic rats. However, the above biochemical events in ghrelin treated diabetic rats were completely inhibited by GHSR-1a blocker [D-Lys3]-GHRP-6. CONCLUSIONS: These results suggest that administration of ghrelin ameliorates impaired angiogenesis in diabetic MI rats. And these beneficial effects derive from regulating GHSR1a mediated AMPK/eNOS signal pathway by upregulating of HIF1alpha, VEGF and its receptors Flk-1, Flt-1 expressions. PMID- 26364515 TI - Donor catch-up growth after laser surgery for twin-twin transfusion syndrome. AB - OBJECTIVE: To assess fetal growth after laser surgery for TTTS at the time of prenatal diagnosis, birth, and at 2years of age. DESIGN/METHODS: Growth data were collected from surviving children treated between 2007 and 2010 as part of a study to assess neurodevelopment at 24months (+/-6weeks) corrected age. Fetal weights were obtained via ultrasound using Hadlock's formula at the time of preoperative assessment for laser surgery. Birth weights were recorded by the staff at the delivering institutions. Weights at 2years corrected age were recorded at the time of neurodevelopmental testing. Weights were converted into percentiles according to standard growth curves. Growth restriction was defined as <10th percentile for given age. Multilevel latent growth curve models in Mplus (twins nested in families) examined weight change over time as a function of donor status, and repeated measures ANOVA was utilized to assess in donor recipient weight discordance over time for twin pairs. RESULTS: 99 of 206 children (56 of 130 families) were studied. There were no differences between enrolled and non-enrolled patients in donor/recipient status and survival rates, fetal demise, intrauterine growth restriction, Quintero stage, and gestational age of surgery or delivery. 48.5% were donors. The median fetal, birth, and 2 year weights for all twins were 288g, 1.9kg, and 11.8kg, respectively, and the overall prevalence of growth restriction was 28%, 22%, and 3%, respectively. Growth restriction rates at prenatal diagnosis were 56% in donors vs. 2% in recipients (OR=64.3, p<0.001); at birth, 35% vs. 10% (OR=5.0, p<0.01); and at 2years, 6% vs. 0%. Donors showed significant gains in weight percentile (B=13.1, p<0.001) and a significant decrease in growth restriction rates over time (B= 1.6, p<0.001). Weight discordance between donor and recipient pairs also significantly decreased over time (linear F(1,42)=54.34, p<0.001). CONCLUSIONS: After laser surgery for TTTS, donor twins exhibit significant catch-up growth by two years of age. PMID- 26364516 TI - Long term survival with cytotoxic T lymphocyte-associated antigen 4 blockade using tremelimumab. AB - PURPOSE: One of the hallmarks of cancer immunotherapy is the long duration of responses, evident with cytokines like interleukin-2 or a variety of cancer vaccines. However, there is limited information available on very long term outcomes of patients treated with anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) antibodies. Tremelimumab is an anti-CTLA-4 antibody of immunoglobulin G2 (IgG2) isotype initially tested in patients with advanced melanoma over 12 years ago. METHODS: We reviewed the outcomes of patients with advanced melanoma enrolled in four phase 1 and 2 tremelimumab trials at two sites to determine response rates and long-term survival. RESULTS: A total of 143 patients were enrolled at two institutions from 2002 to 2008. Tremelimumab administration varied between a single dose of 0.01 mg/kg and 15 mg/kg every 3 months. Median overall survival was 13 months (95% confidence interval (CI), 10-16.6), ranging from less than a month to 12+ years. An objective response rate of 15.6% was observed, with median duration of response of 6.5 years, range of 3-136+ months. The Kaplan-Meier estimated 5 year survival rate was 20% (95% CI, 13-26%), with 10 and 12.5 year survival rates of 16% (95% CI, 9-23%). CONCLUSIONS: CTLA-4 blockade with tremelimumab can lead to very long duration of objective anti-tumour responses beyond 12 years. PMID- 26364517 TI - Bayesian network meta-comparison of maintenance treatments for stage IIIb/IV non small-cell lung cancer (NSCLC) patients with good performance status not progressing after first-line induction chemotherapy: results by performance status, EGFR mutation, histology and response to previous induction. AB - BACKGROUND: Recent trials have suggested that maintenance treatments improve outcomes for patients not progressing after first-line therapy for advanced non small-cell lung cancer (NSCLC). However, physicians have little guidance on selecting which patients benefit the most and what drug or regimen is optimal. Here, we report a systematic review and network meta-analysis of maintenance treatments in subgroups determined by performance status (PS), epidermal growth factor receptor (EGFR) mutation, histology and response to induction. METHODS: PubMed and conference proceedings were reviewed and individual study relative efficacy measures were meta-analysed in a Bayesian hierarchical model. The primary outcome, overall survival (OS), was evaluated in terms of (i) posterior surface under cumulative ranking curve (SUCRA), (ii) probability of being best treatment, (iii) probability of outperforming no maintenance, and (iv) posterior median hazard ratio (95% credible interval). Secondary outcomes were progression free survival (PFS) and adverse events. FINDINGS: Twelve trials evaluating eight maintenance treatments in 3850 patients were meta-analysed. Selected maintenance treatments showed clinically meaningful benefits of ?20% reduction in hazards of death with ?90% probability of outperforming no maintenance in terms of OS: (i) switch to or continue pemetrexed (nonsquamous), continue gemcitabine, or switch to EGFR tyrosine kinase inhibitors (TKIs) for PS 0 patients, (ii) switch to pemetrexed (nonsquamous) for PS 1 patients, (iii) switch to EGFR TKI for EGFR mutation positive patients, (iv) switch to or continue pemetrexed or switch to EGFR TKI for nonsquamous patients, (v) continue gemcitabine for squamous patients, (vi) switch to docetaxel or continue gemcitabine for responders to induction, or (vii) switch to or continue pemetrexed (nonsquamous) or switch to EGFR TKI for patients with stable disease post-induction. INTERPRETATION: Maintenance treatments show clinically meaningful survival benefits in good performance status patients with advanced NSCLC not progressing after first-line chemotherapy. Benefits are optimised by targeting specific maintenance to individual patients guided by PS, EGFR mutation status, histology and response to induction. PMID- 26364518 TI - Gemcitabine, capecitabine and oxaliplatin with or without cetuximab in advanced biliary tract carcinoma. PMID- 26364519 TI - Knowledge, attitude and practice of health care providers toward Ebola virus disease in hotspots in Khartoum and White Nile states, Sudan, 2014. AB - BACKGROUND: Ebola virus disease (EVD) is an infectious disease associated with a high fatality rate. Health care providers (HCPs) are frequently infected while treating patients with suspected or confirmed EVD. Knowledge of, attitudes toward, and practices of HCP toward EVD, especially in hot spots, is an essential element to control the disease. MATERIALS AND METHODS: In this descriptive, cross sectional, health facility-based study, 258 HCPs were interviewed in different health facilities in hot spots in the targeted states, including district and federal hospitals and health centers, using a self-administrated questionnaire. RESULTS: The majority of respondents were house officers (40.7%), followed by nurses (26.4%). The remaining respondents were registrars, medical officers, and allied health professionals. All participants had heard about EVD. There were significant differences in the knowledge of doctors and allied health care providers regarding modes of transmission and clinical manifestations. Some false information, such as airborne transmission (53.1%) and insect transmission (20.2%), was reported by respondents. The majority of respondents (81.3%) claimed that they would treat patients with suspected EVD while taking a safe approach, 83.5% said they would notify health authorities about cases of suspected EVD, and 91.1% reported not attending any training sessions about EVD. CONCLUSION: The media plays an important role in increasing awareness about EVD. Regardless, however, researchers recommend more in-service training for HCPs to increase their knowledge about EVD. PMID- 26364520 TI - Control of extended-spectrum beta-lactamase-producing Enterobacteriaceae nosocomial acquisition in an intensive care unit: A time series regression analysis. AB - BACKGROUND: This study was undertaken to determine the temporal relationship between implementation of different interventions in an intensive care unit (ICU) and control of endemic nosocomial acquisition of extended-spectrum beta-lactamase Enterobacteriaceae (ESBLE). METHODS: This was a prospective observational study with time-series analysis of the monthly incidence of ESBLE and its predictors. In November 2007, after a 14-month baseline period, an intervention consisting of restriction of third-generation cephalosporins (3 GC) and increased use of alcohol-based hand rubs was implemented. In January 2008, an increased health care worker (HCW):patient ratio was also implemented. In March 2010, the ICU was closed, and patients were moved to a clean ICU. RESULTS: The first intervention resulted in global reduction in 3 GC and increased use of alcohol-based hand rub. A significant change in ESBLE incidence was observed in a full segmented univariate regression analysis (mean change in level, -0.91 +/- 0.19; P < .0001). After ICU closure, there was a dramatic reduction in ESBLE acquisition. According to the multivariate model, the ICU closure was the main protective factor. Before ICU closure, an increase in the HCW:patient ratio of 0.1 point tended to be associated with a decreased risk of ESBLE acquisition (relative risk, 0.28; 95% confidence interval, 0.06-1.25; P = .09). CONCLUSIONS: This study shows that ICU closure was associated with, but not necessarily the reason for, control of ESBLE cross-transmission in a nonoutbreak setting. Environmental ESBE sources may play a role in cross-transmission. PMID- 26364521 TI - Asthma camp referrals--letter to the editor. PMID- 26364522 TI - [Effects of Nursing Interventions for Fall Prevention in Hospitalized Patients: A Meta-analysis]. AB - PURPOSE: The purpose of this study was to identify which nursing interventions are the most effective in fall prevention for hospitalized patients. METHODS: From 3,675 papers searched, 34 were selected for inclusion in the meta-analysis. Number of fallers, falls, falls per 1,000 hospital-days, and injurious falls, fall protection activity, knowledge related to falls, and self-efficacy about falls were evaluated as outcome variables. Data were analyzed using the Comprehensive Meta Analysis (CMA) 2.2 Version program and the effect sizes were shown as the Odd Ratio (OR) and Hedges's g. RESULTS: Overall effect size of nursing interventions for fall prevention was OR=0.64 (95% CI: 0.57~0.73, p<.05) and Hedges's g=-0.24. The effect sizes (OR) of each intervention ranged from 0.34 to 0.93, and the most effective nursing intervention was the education & environment intervention (OR=0.34, 95% CI: 0.28~0.42, p<.001), followed by education intervention (OR=0.57, 95% CI: 0.50~0.67, p=.001). Subgroup analyses showed that multifaceted interventions (OR=0.76, 95% CI: 0.73~0.79, p<.001) were more effective than unifactorial interventions, and that activities for prevention of falls (OR=0.08, 95% CI: 0.05~0.15, p<.001) showed the largest effect size among outcome variables. CONCLUSION: Falls in hospitalized patients can be effectively prevented using the nursing interventions identified in this study. These findings provide scientific evidence for developing and using effective nursing interventions to improve the safety of hospitalized patients. PMID- 26364523 TI - [Effects of Dietary and Physical Activity Interventions on Metabolic Syndrome: A Meta-analysis]. AB - PURPOSE: This study identified effects of dietary and physical activity interventions including dietary interventions or physical activity interventions alone or combined dietary-physical activity interventions to improve symptoms in metabolic syndrome including abdominal obesity, high triglycerides, low high density lipoprotein cholesterol, elevated blood pressure, and elevated fasting glucose through meta-analysis. METHODS: Articles on metabolic syndrome X published from 1988 to 2013 were searched through electronic databases, Google Scholar, and reference reviews. Methodological quality was assessed by the checklist, SIGN (Scottish Intercollegiate Guidelines Network). RESULTS: In the meta-analysis, there were 9 articles reporting 13 interventions with 736 participants. Using random effect models, the dietary and/or physical activity interventions showed a lower mean difference in waist circumference (-1.30 cm, 95% CI:-2.44~-0.15, p=.027). The combined dietary-physical activity interventions showed a lower mean difference in waist circumference (-2.77 cm, 95% CI:-4.77~ 0.76, p=.007) and systolic blood pressure (-5.44 mmHg, 95% CI:-10.76~-0.12, p=.044). Additionally, interventions of over 24 weeks yielded a lower mean difference in waist circumference (-2.78 cm, 95% CI:-4.69~-0.87, p=.004) and diastolic blood pressure (-1.93 mmHg, 95% CI:-3.63~-0.22, p=.026). CONCLUSION: The findings indicate that dietary and/or physical activity interventions for metabolic syndrome reduce central obesity with no adverse effects. This finding provides objective evidences for dietary and physical activity management on metabolic syndrome as an efficient intervention. PMID- 26364524 TI - Implementing Evidence into Practice for Best Dementia Care. AB - PURPOSE: The purpose of this paper was to discuss the need for translation studies in dementia care and current translational endeavors, and to provide recommendations for evolving evidence-based dementia care. METHODS: A literature review yielded current evidence and translational efforts. RESULTS: Dementia care interventions need to be implemented at various service levels. Barriers to translation include evidence gaps, lack of the use of a conceptual framework to explain the implementation process, and unsupportive funding mechanisms for applying innovations. CONCLUSION: There is clear evidence of the need for and benefits of evidence-based dementia care for patients with dementia, family caregivers, and care professionals. The urgent need now is finding ways to advance translational activities and facilitate future research into translation science. PMID- 26364526 TI - [Nurses' Experiences of the Death of Patients in Geriatric Hospitals]. AB - PURPOSE: The purpose of this study was to identify and understand nurses' experiences of the death of patients in geriatric hospitals. METHODS: Van Manen's hermeneutic phenomenological analysis was applied in the interpretation of experiential descriptions of seven nurses who had experienced the death of patients in a geriatric hospital. RESULTS: The essential subjects derived from the experience of the nurses on the death of patients in a geriatric hospital are covered in the following 7 themes. 'Placed in death site', 'Difficult repetition of death and farewell', 'Emotional waves that rushes in after farewell', 'Dilemmas in a place with no preparation to greet expected death', 'Getting dull from continually being struck with sorrow', 'Being together with living death', and 'Showing courtesy for a good farewell and living well'. CONCLUSION: The results of this research will contribute to the development of policy on all the deaths of patients in geriatric hospitals and suggest basic data that need to be applied in real practice and directions to introduce plans for realistic improvements in nursing care of deathbed patients in geriatric hospitals. PMID- 26364525 TI - [Adaptation in Families of Children with Down Syndrome: A Mixed-methods Design]. AB - PURPOSE: The purpose of this study, which was guided by the Resiliency Model of Family Stress, Adjustment, and Adaptation, was twofold: (a) to explore family and parental adaptation and factors influencing family adaptation in Korean families of children with Down syndrome (DS) through a quantitative methodology and (b) to understand the life with a Korean child with DS through a qualitative method. METHODS: A mixed-methods design was adopted. A total of 147 parents of children with DS completed a package of questionnaires, and 19 parents participated in the in-depth interviews. Quantitative and qualitative data were analyzed using stepwise multiple regression and content analysis respectively. RESULTS: According to the quantitative data, the overall family adaptation scores indicated average family functioning. Financial status was an important variable in understanding both family and parental adaptation. Family adaptation was best explained by family problem solving and coping communication, condition management ability, and family hardiness. Family strains and family hardiness were the family factors with the most influence on parental adaption. Qualitative data analysis showed that family life with a child with DS encompassed both positive and negative aspects and was expressed with 5 themes, 10 categories, and 16 sub-categories. CONCLUSION: Results of this study expand our limited knowledge and understanding concerning families of children with DS in Korea and can be used to develop effective interventions to improve the adaptation of family as a unit as well as parental adaptation. PMID- 26364527 TI - [Identifying Usability Level and Factors Affecting Electronic Nursing Record Systems: A Multi-institutional Time-motion Approach]. AB - PURPOSE: The usability, user satisfaction, and impact of electronic nursing record (ENR) systems were investigated. METHODS: This mixed-method research was performed as a time-motion (TM) study and a survey which were carried out at six hospitals between August and November 2013. The TM study involved 108 nurses from medical, surgical, and intensive care units at each hospital, plus an additional 48 nurses who served as nonparticipating observers. In the survey, 1879 volunteer nurses completed the Impact of ENR Systems Scale, the System Usability Scale, and a global satisfaction scale. Qualitative and quantitative analyses were performed. RESULTS: The mean scores for the ENR impact, system usability, and satisfaction were 4.28 (out of 6), 58.62 (out of 100), and 74.31 (out of 100), respectively, and they differed significantly between hospitals (F=43.43, p<.001, F=53.08 and p<.001, and F=29.13 and p<.001, respectively). A workflow fragmentation assessment revealed different patterns of ENR system use among the included hospitals. Three user characteristics-educational background, practice period, and experience of using paper records-significantly affected the system usability and satisfaction scores. CONCLUSION: The system quality varied widely among the ENR systems. The generally low-to-moderate levels of system usability and user satisfaction suggest many opportunities for improvement. PMID- 26364528 TI - [Development and Effects of a Motivational Interviewing Self-management Program for Elderly Patients with Diabetes Mellitus]. AB - PURPOSE: This study was conducted to develop and test the effects of a motivational interviewing self-management program for use with elderly patients with diabetes mellitus. METHODS: A non-equivalent control group pretest-posttest design was used. The participants were 42 elderly diabetic patients (experimental group: 21, control group: 21). The motivational interviewing self-management program for elders with diabetes mellitus developed in this study consisted of a 12-week program in total (8 weeks for group motivational interviewing and education and 4 weeks for individual motivational interviewing on the phone). Data were collected between February 13 and May 3, 2013 and were analyzed using t test, paired t-test, and repeated measure ANOVA with SPSS/WIN 18.0. RESULTS: For the experimental group, significant improvement was found for self-efficacy, self care behavior, glycemic control and quality of life (daily life satisfaction, influence of disease) as compared to the control group. CONCLUSION: The study findings indicate that the motivational interviewing self-management program is effective and can be recommended as a nursing intervention for elderly patients with diabetes mellitus. PMID- 26364529 TI - [Validity and Reliability of ARQ-K (Korean Version of the Assault Response Questionnaire) for Emergency Department Nurses in Korea]. AB - PURPOSE: To investigate the validity and reliability of the Korean Version of the Assault Response Questionnaire (ARQ-K) measuring the intensity of reaction to victimization of emergency nurses in Korea. METHODS: An internal consistency reliability and construct validity using exploratory and confirmatory factor analysis were conducted using SPSS WIN (20.0) and AMOS (20.0). Survey data were collected from 321 nurses who worked in 3 levels - wide regional emergency centers, regional emergency centers, appointed emergency centers - of emergency care facilities in Busan, Korea. RESULTS: The Cronbach's alpha values regarding internal consistency were .77~.93 for the subscales of ARQ-K. Factor loadings of the 26 items on the four subscales ranged from .59 to .84. The four-subscale model was validated by confirmatory factor analysis (chi2/df=3.85, p<.001, RMR=.06, GFI=.80, NFI=.81, TLI=.83, CFI=.85, RMSEA=.09). CONCLUSION: This study shows that the Korean Version of the Assault Response Questionnaire is a valid and reliable instrument to assess nurses' reaction to victimization of emergency nurses in Korea. PMID- 26364530 TI - [Development and Application of a Self-management Program based on Prothrombin INR Monitoring for Patients with Cardiac Valve Replacement]. AB - PURPOSE: The purpose of this study was to develop and evaluate a self-management program based on INR monitoring for patients with cardiac valve replacement. METHODS: This program was comprised of five weekly sessions based on Sousa's Enhance-Behavior Performance Model. The first session included individual teaching, and the other four sessions included Prothrombin Time International Normalized Ratios (PT INR) self-monitoring, telephone counseling and self management checklist recording. Participants were patients who had cardiac valve replacement. They were randomly assigned to the experimental or control group. Sixteen in the experimental group participated in the self-management program and seventeen in the control group participated in general care. Self-management knowledge, self-efficacy, self-management behavior and PT INR were measured as dependent variables. Data were analyzed using Mann Whitney U-test, t-test and ANCOVA. RESULTS: The experimental group showed significantly higher post-test scores in self-management knowledge (t=5.86, p<.001), self-efficacy (F=18.32, p<.001), and self-management behavior (t=3.44, p=.002) compared to the control group. Also, the experimental group showed significantly higher frequency in maintaining the treatment range of PT INR compared to the control group (chi2=4.80, p=.028). CONCLUSION: The results of the research on the self management program based on PT INR monitoring showed that it is effective in improving self-management knowledge, self-efficacy, and self-management behavior as well as maintaining treatment range of PT INR of patients with cardiac valve replacement. PMID- 26364531 TI - [Analysis of Mission Statements and Organizational Performance of Hospitals in South Korea]. AB - PURPOSE: The purpose of the study was to examine mission statements and their elements and to investigate correlations between mission statements and organizational performance. METHODS: The current research was a descriptive study based on the examination of mission statements of 353 hospitals that posted mission statements on their webpage and 92 hospitals that made their income statements public. RESULTS: The most common mission element was 'identification of principal services', which accounted for 92.6%. Mission statements of hospitals included the average of 4.82 mission elements out of 9, and the objective of medical quality improvement was 0.81 among 6 objectives of IOM (Institute of Medicine). Net profit of hospitals with mission statements that have above average number of mission elements were significantly higher (t=2.71, p=.008) than those of other hospitals. Net profit was significantly correlated with mission statements (r=.26, p<.001), and mission elements (r=.29, p<.001). CONCLUSION: The results of the study empirically reveal that mission statements in the hospital affect organizational performance. That is, better organizational performance is shown for hospitals with better, more diversified, and more firmly stated mission statements which include identification of target customers, identification of principal services, contribution to society as a non-profit organization, and concern for employees. PMID- 26364532 TI - [Effects of Self-management Program applying Dongsasub Training on Self-efficacy, Self-esteem, Self-management Behavior and Blood Pressure in Older Adults with Hypertension]. AB - PURPOSE: The purpose of this study was to develop a self-management program applying Dongsasub training based on self-efficacy theory, and to verify the program effectiveness on self-esteem as well as self-efficacy, self-management behaviors, and blood pressure. METHODS: The study design was a non-equivalent, pre-post controlled quasi-experiment study. Thirty-eight patients aged 65 and older from a senior welfare center in Seoul participated in this study (20 patients in the experimental group and 18 patients in the control group). The self-management program applying Dongsasub training consisted of eight sessions. After development was complete the program was used with the experimental group. Outcome variables included self-efficacy, self-esteem, self-management behaviors measured by questionnaires, and blood pressure measured by electronic manometer. RESULTS: Self-efficacy (t=2.42, p=.021), self-esteem (t=2.57, p=.014) and self management behaviors (t=2.21, p=.034) were significantly higher and systolic blood pressure (t=-2.14, p=.040) was significantly lower in the experimental group compared to the control group. However, diastolic blood pressure (t=-.85, p=.400) was not significantly different between the two groups. CONCLUSION: The results indicate that the self-management program applying Dongsasub training can be used as a nursing intervention in community settings for improving self management behaviors for older adults with hypertension. PMID- 26364533 TI - [Effects of Foot-Reflexology Massage on Fatigue, Stress and Postpartum Depression in Postpartum Women]. AB - PURPOSE: To identify the effects of foot reflexology massage on fatigue, stress and depression of postpartum women. METHODS: A nonequivalent control group pre post design was used. A total of 70 women in a postpartum care center were recruited and were assigned to the experimental group (35) or control group (35). Foot reflexology massage was provided to the experimental group once a day for three days. Data were collected before and after the intervention program which was carried out from December, 2013 to February, 2014. Data were analyzed using Chi-square test, Fisher's exact test, and t-test. RESULTS: The level of fatigue in the experimental group was significantly lower than the control group (t= 2.74, p=.008). The level of cortisol in the urine of women in the experimental group was significantly lower than the control group (t=-2.19, p=.032). The level of depression in the experimental group was significantly lower than the control group (t=-3.00, p=.004). CONCLUSION: The results show that the foot reflexology massage is an effective nursing intervention to relieve fatigue, stress, and depression for postpartum women. PMID- 26364534 TI - [Predictors of Resilience in Adolescents with Leukemia]. AB - PURPOSE: The purpose of this study was to identify the factors relating to resilience for adolescents with leukemia and examine the relationship between these factors. METHODS: From June to September in 2014, 199 adolescents aged 11 to 21 participated in the study as they visited the out-patient clinic at C university hospital for follow-up care. To verify the predictors and the effects of resilience, uncertainty, symptom distress, perceived social support, spiritual perspective, defensive coping, courageous coping, hope, and self-transcendence were measured. Collected data were analyzed using hierarchical regression analysis with the SAS statistics program. RESULTS: The final regression model showed that courageous coping, hope, and self-transcendence were significant predictors related to resilience in adolescents with leukemia and explained for 63% of the variance in resilience. CONCLUSION: The findings indicate that adolescent-oriented intervention programs enhancing courageous coping, hope, and self-transcendence should be provide for adolescents with leukemia in order to overcome illness-related stress and support physical, psychological and social adjustment. PMID- 26364535 TI - [Factors Influencing Quality of Life during Chemotherapy for Colorectal Cancer Patients in South Korea]. AB - PURPOSE: The purpose of this study was to investigate the levels of physical symptoms, anxiety, depression, and quality of life (QOL) during chemotherapy for colorectal cancer patients in South Korea and to identify factors influencing their QOL. METHODS: Data were collected from 144 colorectal cancer patients receiving chemotherapy during 2012 at one general hospital located in Seoul. Physical symptoms were measured by the M. D. Anderson Symptom Inventory Gastrointestinal Cancer Module, and anxiety and depression were measured by the Hospital Anxiety Depression Scale. QOL was measured by the Functional Assessment of Cancer Therapy-Colorectal. Data were analyzed using descriptive statistics, t test, one-way ANOVA, Scheffe post hoc test, Pearson correlation and stepwise multiple regression. RESULTS: Mean age of the participants was 56.6 and most of them were not employed. In terms of cancer stage, 38.2% were in stage 3, followed by stage 4 (34.7%). The most frequent symptom was lack of appetite, followed by sleep disturbance and fatigue. The mean score for anxiety was 5.40 with a prevalence of 23% and that of depression 8.85 with a prevalence of 64.6%. The mean score for quality of life was 81.93 out of 136 and 75.3% of the variance in QOL was explained by depression, symptoms, anxiety, treatment place, and occupational status. Depression was the strongest predictive factor. CONCLUSION: Oncology professionals need to pay special attention to relieving depression as well as physical symptoms to improve QOL during chemotherapy for colorectal cancer patients. PMID- 26364536 TI - [Development and Validation of the Empowerment Scale for Woman with Breast Cancer]. AB - PURPOSE: The purpose of this study was to develop a scale to evaluate empowerment in woman with breast cancer and to examine the validity and reliability of the scale. METHODS: The development process for the initial items included a literature review, interviews, and construction of a conceptual framework. The identified items were evaluated for content validity by experts, resulting in 3 factors and 48 preliminary items. Participants were 319 women with breast cancer recruited to test reliability and validity of the preliminary scale. Data were analyzed using item analysis, confirmatory factor analysis, criterion related validity, internal consistency and test-retest reliability. RESULTS: The final scale consisted of 30 items and 3 factors. Factors, including 'intrapersonal factor' (14 items), 'interactional factor' (8 items), and 'behavioral factor' (8 items), were drawn up after confirmatory factor analysis. Goodness of fit of the final research model was very appropriate as shown by chi2/df=1.86, TLI=.90, CFI=.92, SRMR=.06, and RMSEA=.05. Criterion validity was evaluated by total correlation with the Cancer Empowerment Questionnaire .78. Cronbach's alpha for total items was .93 and test-retest reliability was .69. CONCLUSION: Findings from this study indicate that the scale can be used in the development of nursing interventions to promote the empowerment of women having breast cancer. PMID- 26364537 TI - [CORRIGENDUM]. PMID- 26364538 TI - Single inhibition of either PDE3 or PDE4 unmasks beta2-adrenoceptor-mediated inotropic and lusitropic effects in the left but not right ventricular myocardium of rat. AB - Cyclic nucleotide phosphodiesterase (PDE)3 and PDE4 provide the major PDE activity in cardiac myocytes and shape beta1-adrenoceptor-dependent cardiac cAMP signaling but their role in regulating beta2-adrenoceptor-mediated responses is less well known. We investigated potential differences in PDE3 and PDE4 activities between right (RV) and left (LV) ventricular myocardium, and their role in regulating beta2-adrenoceptor effects. PDE3 activity in the microsomal fraction was lower in RV than in LV but was the same in the cytosolic fraction. However, no significant difference between RV and LV was found when the PDE4 activity was studied. beta2-adrenoceptor activation increased inotropism and lusitropism in LV when measured in the presence of either the PDE3 inhibitor cilostamide, the PDE4 inhibitor rolipram or a non-selective PDE inhibitor IBMX. However, the joint inhibition of both PDE3 and PDE4 was necessary in RV to uncover beta2-adrenoceptor-induced inotropic and lusitropic effects. Our results indicate different regulation of beta2-adrenoceptor-mediated contractility by PDE3 and PDE4 in RV and LV of the rat heart. In the case of PDE3 due to a different contribution of the enzyme in the microsomal fraction whereas in the case of PDE4 it can be attributed to differences in the intracellular distribution and coupling to beta2-adrenoceptors. PMID- 26364539 TI - Host switching vs. host sharing in overlapping sylvatic Trypanosoma cruzi transmission cycles. AB - The principle of competitive exclusion is well established for multiple populations competing for the same resource, and simple models for multistrain infection exhibit it as well when cross-immunity precludes coinfections. However, multiple hosts provide niches for different pathogens to occupy simultaneously. This is the case for the vector-borne parasite Trypanosoma cruzi in overlapping sylvatic transmission cycles in the Americas, where it is enzootic. This study uses cycles in the USA involving two different hosts but the same vector species as a context for the study of the mechanisms behind the communication between the two cycles. Vectors dispersing in search of new hosts may be considered to move between the two cycles (host switching) or, more simply, to divide their time between the two host types (host sharing). Analysis considers host switching as an intermediate case between isolated cycles and intermingled cycles (host sharing) in order to examine the role played by the host-switching rate in permitting coexistence of multiple strains in a single-host population. Results show that although the population dynamics (demographic equilibria) in host switching models align well with those in the limiting models (host sharing or isolated cycles), infection dynamics differ significantly, in ways that sometimes illuminate the underlying epidemiology (such as differing host susceptibilities to infection) and sometimes reveal model limitations (such as host switching dominating the infection dynamics). Numerical work suggests that the model explains the trace presence of TcI in raccoons but not the more significant co persistence observed in woodrats. PMID- 26364540 TI - Rethinking environmental influences on child language development. PMID- 26364541 TI - Oncocytic parathyroid adenoma. AB - INTRODUCTION: Fine-needle aspiration cytology (FNAC) of thyroid nodules commonly reveals the presence of oncocytic cells (or Hurthle cells) in a follicular neoplasm. Histological examination is necessary to determine the benign or malignant nature of the tumour. However, oncocytic cells are also normally present in the parathyroid glands. CASE REPORT: A thyroid nodule was discovered on thyroid ultrasound in a woman with a history of left partial thyroid lobectomy. Fine-needle aspiration cytology revealed a follicular neoplasm comprising oncocytic cells (Hurthle cells). This woman also presented features of hyperparathyroidism with hypercalcaemia. (123)I/(99m)Tc-sestamibi and (18)F fluorocholine PET-CT scan revealed increased uptake over the remaining left thyroid lobe. Left lobectomy was completed together with thyroid exploration. Histological examination revealed a parathyroid adenoma in the residual thyroid tissue. Parathyroid hormone levels subsequently returned to normal. DISCUSSION: Cytomorphological similarities are often observed between parathyroid and Hurthle cell thyroid tumours. The parathyroid rather than thyroid nature of the tumour must be strongly suspected preoperatively in the presence of hyperparathyroidism. PMID- 26364542 TI - Nasal foreign bodies: Results of a study of 260 cases. AB - AIMS: Insertion of a foreign body in the nasal cavity is a very common incident in children. It is easily diagnosed, but the type of foreign body varies and extraction can sometimes be difficult, with risk of complications. The present study reports nasal foreign bodies seen in emergency in our ENT department, with an update on the state of knowledge. MATERIALS AND METHODS: A prospective study between May and August 2011 included all patients admitted to the ENT emergency unit for nasal foreign body. Data comprised age, gender, circumstances of discovery, symptoms, type of foreign body, extraction method and complications. RESULTS: Two hundred and sixty cases of nasal foreign body were included, representing 4.3% of all consultations in the unit. Mean age was 3 years (range: 1-16 years); the sex ratio was 1.4 (male predominance). The incident was reported by a family member or the actual child in 76.9% of cases (n=199), or discovered following nasal symptoms in 23.1% (n=61). The main types of foreign body were non organic synthetic beads in 18.8% of cases and vegetable forms in 17.7%. Extraction was easy, using forceps, micro-hooks or suction, in 91.53% of cases. Complications comprised infection (n=48), epistaxis (n=18) and nasal septum perforation (n=1). CONCLUSION: Nasal foreign bodies are a frequent accident in medical practice, especially in young children. They are generally harmless, but may incur complications if overlooked or when a button cell is involved, whence the importance of timely extraction. The best treatment, however, remains prevention. PMID- 26364543 TI - How can we reduce the global burden of disease? PMID- 26364545 TI - Hypertrichosis lanuginosa acquisita: a rare dermatological disorder. PMID- 26364546 TI - Primary biliary cirrhosis. AB - Primary biliary cirrhosis is a chronic cholestatic liver disease characterised by destruction of small intrahepatic bile ducts, leading to fibrosis and potential cirrhosis through resulting complications. The serological hallmark of primary biliary cirrhosis is the antimitochondrial antibody, a highly disease-specific antibody identified in about 95% of patients with primary biliary cirrhosis. These patients usually have fatigue and pruritus, both of which occur independently of disease severity. The typical course of primary biliary cirrhosis has changed substantially with the introduoction of ursodeoxycholic acid (UDCA). Several randomised placebo-controlled studies have shown that UDCA improves transplant-free survival in primary biliary cirrhosis. However, about 40% of patients do not have a biochemical response to UDCA and would benefit from new therapies. Liver transplantation is a life-saving surgery with excellent outcomes for those with decompensated cirrhosis. Meanwhile, research on nuclear receptor hormones has led to the development of exciting new potential treatments. This Seminar will review the current understanding of the epidemiology, pathogenesis, and natural history of primary biliary cirrhosis, discuss management of the disease and its sequelae, and introduce research on new therapeutic options. PMID- 26364547 TI - Regulator of G-Protein Signaling 7 Regulates Reward Behavior by Controlling Opioid Signaling in the Striatum. AB - BACKGROUND: Morphine mediates its euphoric and analgesic effects by acting on the MU-opioid receptor (MOR). MOR belongs to the family of G-protein coupled receptors whose signaling efficiency is controlled by the regulator of G-protein signaling (RGS) proteins. Our understanding of the molecular diversity of RGS proteins that control MOR signaling, their circuit specific actions, and underlying cellular mechanisms is very limited. METHODS: We used genetic approaches to ablate regulator of G-protein signaling 7 (RGS7) both globally and in specific neuronal populations. We used conditioned place preference and self administration paradigms to examine reward-related behavior and a battery of tests to assess analgesia, tolerance, and physical dependence to morphine. Electrophysiology approaches were applied to investigate the impact of RGS7 on morphine-induced alterations in neuronal excitability and plasticity of glutamatergic synapses. At least three animals were used for each assessment. RESULTS: Elimination of RGS7 enhanced reward, increased analgesia, delayed tolerance, and heightened withdrawal in response to morphine administration. RGS7 in striatal neurons was selectively responsible for determining the sensitivity of rewarding and reinforcing behaviors to morphine without affecting analgesia, tolerance, and withdrawal. In contrast, deletion of RGS7 in dopaminergic neurons did not influence morphine reward. RGS7 exerted its effects by controlling morphine-induced changes in excitability of medium spiny neurons in nucleus accumbens and gating the compositional plasticity of alpha-amino-3-hydroxy-5 methyl-4-isoxazole propionic acid and N-methyl-D-aspartate receptors. CONCLUSIONS: This study identifies RGS7 as a novel regulator of MOR signaling by dissecting its circuit specific actions and pinpointing its role in regulating morphine reward by controlling the activity of nucleus accumbens neurons. PMID- 26364549 TI - Arthroscopic Repair for Chronic Massive Rotator Cuff Tears: A Systematic Review. AB - PURPOSE: To systematically review the available evidence for arthroscopic repair of chronic massive rotator cuff tears and identify patient demographics, pre- and post-operative functional limitations, reparability and repair techniques, and retear rates. METHODS: Medline, Embase, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials were searched to identify all clinical papers describing arthroscopic repair of chronic massive rotator cuff tears. Papers were excluded if a definition of "massive" was not provided, if the definition of "massive" was considered inappropriate by agreement between the 2 reviewers, or if patients with smaller tears were also included in the study population. Study quality and clinical outcome data were pooled and summarized. RESULTS: There were 18 papers that met the eligibility criteria; they involved 954 patients with a mean age of 63 (range, 37 to 87), 48% of whom were female. There were 5 prospective and 13 retrospective study designs. The overall study quality was poor according to the Modified Coleman Methodology Score. Of the 954 repairs, 81% were complete repairs and 19% were partial repairs. The follow-up range was between 33 and 52 months, and the mean duration between symptom onset and surgery was 24 months. Single-row repairs were performed in 56% or patients, and double-row repairs were performed in 44%. A pooled analysis demonstrated an improvement in visual analog scale from 5.9 to 1.7, active range of motion from 125 degrees to 169 degrees , and the Constant Murley score from 49 to 74. The pooled retear rate was 79%. CONCLUSIONS: Arthroscopic repair of chronic massive rotator cuff tears is associated with complete repair in the majority of cases and consistently improves pain, range of motion, and functional outcome scores; however, the retear rate is high. Existing research on massive rotator cuff repair is limited to poor- to fair-quality studies. LEVEL OF EVIDENCE: Level IV, systematic review including Level IV studies. PMID- 26364548 TI - Markedly Lower Glutamic Acid Decarboxylase 67 Protein Levels in a Subset of Boutons in Schizophrenia. AB - BACKGROUND: Convergent findings indicate that cortical gamma-aminobutyric acid (GABA)ergic circuitry is altered in schizophrenia. Postmortem studies have consistently found lower levels of glutamic acid decarboxylase 67 (GAD67) messenger RNA (mRNA) in the prefrontal cortex (PFC) of subjects with schizophrenia. At the cellular level, the density of GABA neurons with detectable levels of GAD67 mRNA is ~30% lower across cortical layers. Knowing how this transcript deficit translates to GAD67 protein levels in axonal boutons is important for understanding the impact it might have on GABA synthesis. In addition, because reductions in GAD67 expression before, but not after, the maturation of GABAergic boutons results in a lower density of GABAergic boutons in mouse cortical cultures, knowing if GABAergic bouton density is altered in schizophrenia would provide insight into the timing of the GAD67 deficit. METHODS: PFC tissue sections from 20 matched pairs of schizophrenia and comparison subjects were immunolabeled for the vesicular GABA transporter (vGAT) and GAD67. RESULTS: vGAT+ bouton density did not differ between subject groups, consistent with findings that vGAT mRNA levels are unaltered in the illness and confirming that the number of cortical GABAergic boutons is not lower in schizophrenia. In contrast, in schizophrenia subjects, the proportion of vGAT+ boutons with detectable GAD67 levels (vGAT+/GAD67+ boutons) was 16% lower and mean GAD67 levels were 14% lower in the remaining vGAT+/GAD67+ boutons. CONCLUSIONS: Our findings suggest that GABA production is markedly reduced in a subset of boutons in the PFC of schizophrenia subjects and that this reduction likely occurs after the maturation of GABAergic boutons. PMID- 26364550 TI - Is Gleason Grade 5 Prostate Cancer Resistant to Conventional Androgen Deprivation Therapy? AB - Synthesis of data from randomized trials suggests that long-term versus short term androgen deprivation therapy may be most effective in men with Gleason grade 4 prostate cancer (PCa) and less or ineffective in men with Gleason grade 5 PCa. PMID- 26364552 TI - Finasteride and Bladder Cancer. PMID- 26364551 TI - A Randomised Phase 2 Study of AZD2014 Versus Everolimus in Patients with VEGF Refractory Metastatic Clear Cell Renal Cancer. AB - BACKGROUND: Everolimus is a mammalian target of rapamycin (mTOR) inhibitor used in vascular endothelial growth factor (VEGF)-refractory metastatic renal cell carcinoma (mRCC). It acts on only part of the mTOR complex (TORC1 alone). In vitro data support the use of mTOR inhibitors with broader activity (TORC1 and TORC2). OBJECTIVE: The purpose of this study was to determine whether combined TORC1 and TORC2 inhibition with AZD2014 has superior activity to everolimus in VEGF-refractory clear cell mRCC. DESIGN, SETTING, AND PARTICIPANTS: Patients with measurable mRCC and VEGF-refractory disease were eligible for this trial. INTERVENTION: Starting in February 2013, patients were randomised (1:1) to AZD2014 (50 mg twice daily) or everolimus (10 mg once daily) until progression of disease at 10 centres across the United Kingdom. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Progression-free survival (PFS) was the primary end point and was compared using the stratified log-rank test. Secondary end points included tolerability, response rates, overall survival (OS), and pharmacokinetics (PK) analysis. The study was planned to recruit 120 patients. RESULTS AND LIMITATIONS: Recruitment into the trial was stopped early (June 2014) due to lack of efficacy of AZD2014. At that point, 49 patients were randomised (26 to AZD2014 and 23 to everolimus). The PFS for AZD2014 and everolimus was 1.8 and 4.6 mo, respectively (hazard ratio: 2.8 [95% confidence interval (CI), 1.2 6.5]; p=0.01). Progression of disease as the best response to therapy was 69% for AZD2014 and 13% for everolimus (p<0.001). Grade 3-4 adverse events (AEs) occurred in 35% of AZD2014 and 48% of everolimus patients (p=0.3). Only 4% of patients stopped AZD2014 due to AEs. PK analysis suggested concentrations of AZD2014 were compatible with the therapeutic range. Final stratified OS hazard ratio at the time of trial closure (January 2015) was 3.1 (95% CI, 1.1-8.4; p<0.02). CONCLUSIONS: The PFS and OS of AZD2014 were inferior to everolimus in this setting despite acceptable AE and PK profiles. PATIENT SUMMARY: There is a strong rationale for testing mTOR inhibitors with a broader spectrum of activity than everolimus in metastatic clear cell renal cell carcinoma. AZD2014 is such an agent, but in this study, it was inferior to everolimus despite its attractive toxicity profile. PMID- 26364553 TI - Proteomic analysis of cerebrospinal fluid in California sea lions (Zalophus californianus) with domoic acid toxicosis identifies proteins associated with neurodegeneration. AB - Proteomic studies including marine mammals are rare, largely due to the lack of fully sequenced genomes. This has hampered the application of these techniques toward biomarker discovery efforts for monitoring of health and disease in these animals. We conducted a pilot label-free LC-MS/MS study to profile and compare the cerebrospinal fluid from California sea lions with domoic acid toxicosis (DAT) and without DAT. Across 11 samples, a total of 206 proteins were identified (FDR<0.1) using a composite mammalian database. Several peptide identifications were validated using stable isotope labeled peptides. Comparison of spectral counts revealed seven proteins that were elevated in the cerebrospinal fluid from sea lions with DAT: complement C3, complement factor B, dickkopf-3, malate dehydrogenase 1, neuron cell adhesion molecule 1, gelsolin, and neuronal cell adhesion molecule. Immunoblot analysis found reelin to be depressed in the cerebrospinal fluid from California sea lions with DAT. Mice administered domoic acid also had lower hippocampal reelin protein levels suggesting that domoic acid depresses reelin similar to kainic acid. In summary, proteomic analysis of cerebrospinal fluid in marine mammals is a useful tool to characterize the underlying molecular pathology of neurodegenerative disease. All MS data have been deposited in the ProteomeXchange with identifier PXD002105 (http://proteomecentral.proteomexchange.org/dataset/PXD002105). PMID- 26364554 TI - Catalytic mechanism and novel receptor binding sites of human parainfluenza virus type 3 hemagglutinin-neuraminidase (hPIV3 HN). AB - The human parainfluenza virus type 3 (hPIV3) hemagglutinin-neuraminidase (HN) has opposing functions of binding sialic acid receptors and cleaving them, facilitating virus release. The crystal structure of hPIV3 HN complexed with the substrate analogue difluorosialic acid (DFSA) revealed that catalysis by HN involves the formation of a covalently linked sialosyl-enzyme intermediate which was trapped along with a transition-state analogue resembling an oxocarbenium ion. This mechanism of enzyme catalysis was also confirmed in the crystal structure of the influenza N9 neuraminidase complexed with DFSA. Additionally, novel secondary receptor binding sites were identified in the hPIV3 HN-DFSA complex including one near the catalytic cavity which upon binding DFSA imposes subtle changes and may help the HN balance the opposing functions. Multiple receptor binding sites may increase avidity to facilitate cell binding and fusion promotion. The secondary receptor binding sites in the paramyxoviruses are so far unique to each virus type. PMID- 26364555 TI - Bohring-Opitz syndrome (BOS) with a new ASXL1 pathogenic variant: Review of the most prevalent molecular and phenotypic features of the syndrome. AB - Bohring-Opitz syndrome (BOS) was first described by Bohring et al. [1999]. The authors reported four cases which had several features in common, including a prominent metopic suture, hypertelorism, exophthalmos, cleft lip and palate, limb anomalies, as well as difficulty feeding with severe developmental delays. In almost 50% of cases that meet the clinical criteria for BOS, de novo frameshift and nonsense mutations in the ASXL1 gene have been detected, suggesting that loss of function of this gene is a major cause. We report on the clinical characterization of one young female patient who was evaluated because of severe developmental delays, failure to thrive, and multiple minor anomalies and was clinically diagnosed with BOS. Whole exome sequencing analysis detected one novel disruptive frameshift mutation in the ASXL1 gene and we were also able to confirm the presence of two CFTR mutations associated with her chronic pancreatitis with acute severe breakthrough attacks requiring multiple ICU admissions. This latter complication of pancreatitis further contributed to the complexity of the clinical presentation and represents an independent genetic finding. Our case report emphasizes the importance of highly specific phenotypic characterization of patients with complex phenotypes before proceeding with molecular studies. That approach will lead to more accurate molecular data interpretation and better clinical genetic diagnosis, particularly for those patients with rare, difficult to-diagnose disorders. PMID- 26364556 TI - The risk of pulmonary embolism and deep venous thrombosis in systemic lupus erythematosus: A general population-based study. AB - OBJECTIVE: To estimate the future risk and time trends of newly diagnosed venous thromboembolism (VTE) in individuals with incident systemic lupus erythematosus (SLE) in the general population. METHODS: Using a population-based database that includes all residents of British Columbia, Canada we conducted a study cohort of all patients with incident SLE and up to 10 age-, sex-, and entry-time-matched individuals from the general population. We compared incidence rates of pulmonary embolism (PE), deep venous thrombosis (DVT), and VTE between the two groups according to SLE disease duration. We calculated hazards ratios (HR), adjusting for confounders. RESULTS: Among 4863 individuals with SLE (86% female; mean age, 48.9 years), the incidence rates (IRs) of PE, DVT, and VTE were 2.58, 3.33, and 5.32 per 1000 person-years, respectively, whereas the corresponding rates in the comparison cohort were 0.67, 0.57, and 1.11 per 1000 person-years. Compared with non-SLE individuals, the multivariable HRs among SLE patients were 3.04 (95% CI: 2.08-4.45), 4.46 (95% CI: 3.11-6.41), and 3.55 (95% CI: 2.69-4.69), respectively. The age-, sex-, and entry-time-matched HRs for PE, DVT, and VTE were highest during the first year after SLE diagnosis [13.57 (95% CI: 7.66-24.02), 11.13 (95% CI: 6.55-18.90), and 12.89 (95% CI: 8.56-19.41), respectively]. CONCLUSION: These findings provide population-based evidence that patients with SLE have a substantially increased risk of VTE, especially in the first year after SLE diagnosis. Awareness and increased vigilance of this potentially fatal, but preventable, complication is recommended. PMID- 26364557 TI - Single-pulsed electromagnetic field therapy increases osteogenic differentiation through Wnt signaling pathway and sclerostin downregulation. AB - Pulsed electromagnetic field (PEMF) therapy has been used for more than three decades to treat bone diseases. The main complaint about using PEMF is that it is time-consuming. Previously, we showed single-pulsed electromagnetic field (SPEMF) applied for 3 min daily increased osteogenic differentiation of mesenchymal stem cells and accelerated bone growth in a long bone defect model. In the current study, we investigated the mechanism of SPEMF to increase osteogenic differentiation in osteoblastic cells. We found that both short-term (SS) and long-term (SL) SPEMF treatment increased mineralization, while alkaline phosphatase (ALP) activity increased during the first 5 days of SPEMF treatment. SS treatment increased gene expression of Wnt1, Wnt3a, Wnt10b, Fzd9, ALP, and Bmp2. Also, SPEMF inhibited sclerostin after 5 days of treatment, and that inhibition was more significant with SL treatment. SL SPEMF increased expression of parathyroid hormone-related protein (PTHrP) but decreased expression of Sost gene, which encodes sclerostin. Together, the early osteogenic effect of SPEMF utilizes the canonical Wnt signaling pathway while the inhibitory effect of long term SPEMF on sclerostin may be attributable to PTHrP upregulation. This study enhances our understanding of cellular mechanisms to support the previous finding and may provide new insight for clinical applications. PMID- 26364558 TI - Authors' reply to the comment on "Resveratrol improves insulin resistance, glucose and lipid metabolism in patients with non-alcoholic fatty liver disease: A randomized controlled trial" by Shihui Chen et al. [Dig. Liver Dis. 2015;47:226 32]. PMID- 26364559 TI - Hypothalamus-pituitary dysfunction is common in patients with stable cirrhosis and abnormal low dose synacthen test. AB - BACKGROUND: Adrenal insufficiency is often present in cirrhosis. We hypothesize that a prolonged adrenocorticotropic hormone (ACTH) stimulus can restore cellular capacity of adrenal glands to secrete cortisol. Aim of our study was to assess adrenal responsiveness to prolonged ACTH stimulation in cirrhotics. METHODS: Prospective observational study in 121 consecutively admitted cirrhotic patients undergoing a low dose short synacthen test and plasma ACTH measurement using a chemiluminescence immunoassay. Long synacthen test was performed if the low dose was abnormal. RESULTS: 46 patients had abnormal low dose short test (38%), and 29 underwent the long test: 41% showed normal response (Group 1), 55% showed delayed response (Group 2) and 1 had abnormal response (4%). Baseline ACTH levels did not significantly differ between the two groups. Median basal cortisol was higher in Group 1 (296 vs. 198 nmol/L; p=0.02). Using ROC curve basal cortisol <254 nmol/L was associated with a delayed long synacthen test response (AUC 0.78, p=0.001) with good accuracy (sensitivity 67%, specificity 81%). CONCLUSION: A delayed cortisol response after a prolonged ACTH stimulation is found in over fifty percent of cirrhotics with abnormal low dose short synacthen test, confirming that the mechanism of hypoadrenalism in these patients could be related both to adrenal cellular dysfunction and hypothalamus-pituitary adrenal axis impairment. PMID- 26364560 TI - Protein Corona Influences Cellular Uptake of Gold Nanoparticles by Phagocytic and Nonphagocytic Cells in a Size-Dependent Manner. AB - The interaction at nanobio is a critical issue in designing safe nanomaterials for biomedical applications. Recent studies have reported that it is nanoparticle protein corona rather than bare nanoparticle that determines the nanoparticle cell interactions, including endocytic pathway and biological responses. Here, we demonstrate the effects of protein corona on cellular uptake of different sized gold nanoparticles in different cell lines. The experimental results show that protein corona significantly decreases the internalization of Au NPs in a particle size- and cell type-dependent manner. Protein corona exhibits much more significant inhibition on the uptake of large-sized Au NPs by phagocytic cell than that of small-sized Au NPs by nonphagocytic cell. The endocytosis experiment indicates that different endocytic pathways might be responsible for the differential roles of protein corona in the interaction of different sized Au NPs with different cell lines. Our findings can provide useful information for rational design of nanomaterials in biomedical application. PMID- 26364561 TI - Timing of broncho-alveolar lavage for galactomannan testing in hematological oncology patients. PMID- 26364562 TI - An unusual case of gallbladder cancer. AB - Pure squamous cell carcinoma (SCC) of gallbladder is a very rare tumour and is responsible for only 3% of the malignant neoplasm of this organ. We report a case of SCC of gallbladder in a 58-year-old woman. Through this new observation, we propose to study the clinicopathologic features, pathogeny and treatment of this rare entity. PMID- 26364544 TI - Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. AB - BACKGROUND: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution. METHODS: Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk-outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990-2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol. FINDINGS: All risks combined account for 57.2% (95% uncertainty interval [UI] 55.8-58.5) of deaths and 41.6% (40.1-43.0) of DALYs. Risks quantified account for 87.9% (86.5-89.3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11.3 million deaths and 241.4 million DALYs, high systolic blood pressure for 10.4 million deaths and 208.1 million DALYs, child and maternal malnutrition for 1.7 million deaths and 176.9 million DALYs, tobacco smoke for 6.1 million deaths and 143.5 million DALYs, air pollution for 5.5 million deaths and 141.5 million DALYs, and high BMI for 4.4 million deaths and 134.0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa. INTERPRETATION: Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks. FUNDING: Bill & Melinda Gates Foundation. PMID- 26364565 TI - Investigation of diffusion length distribution on polycrystalline silicon wafers via photoluminescence methods. AB - Characterization of the diffusion length of solar cells in space has been widely studied using various methods, but few studies have focused on a fast, simple way to obtain the quantified diffusion length distribution on a silicon wafer. In this work, we present two different facile methods of doing this by fitting photoluminescence images taken in two different wavelength ranges or from different sides. These methods, which are based on measuring the ratio of two photoluminescence images, yield absolute values of the diffusion length and are less sensitive to the inhomogeneity of the incident laser beam. A theoretical simulation and experimental demonstration of this method are presented. The diffusion length distributions on a polycrystalline silicon wafer obtained by the two methods show good agreement. PMID- 26364564 TI - Exploring causal associations of alcohol with cardiovascular and metabolic risk factors in a Chinese population using Mendelian randomization analysis. AB - Observational studies suggest that moderate alcohol consumption may be protective for cardiovascular disease, but results may be biased by confounding and reverse causality. Mendelian randomization, which uses genetic variants as proxies for exposures, can minimise these biases and therefore strengthen causal inference. Using a genetic variant in the ALDH2 gene associated with alcohol consumption, rs671, we performed a Mendelian randomization analysis in 1,712 diabetes cases and 2,076 controls from Nantong, China. Analyses were performed using linear and logistic regression, stratified by sex and diabetes status. The A allele of rs671 was strongly associated with reduced odds of being an alcohol drinker in all groups, but prevalence of alcohol consumption amongst females was very low. The A allele was associated with reduced systolic and diastolic blood pressure and decreased total and HDL cholesterol in males. The A allele was also associated with decreased triglyceride levels, but only robustly in diabetic males. There was no strong evidence for associations between rs671 and any outcomes in females. Our results suggest that associations of alcohol consumption with blood pressure and HDL-cholesterol are causal. Alcohol also appeared to have adverse effects on triglyceride levels, although this may be restricted to diabetics. PMID- 26364566 TI - Overmodulation of projections as signal-to-noise enhancement method in EPR imaging. AB - A study concerning the image quality in electron paramagnetic resonance imaging in two-dimensional spatial experiments is presented. The aim of the measurements was to improve the signal-to-noise ratio (SNR) of the projections and the reconstructed image by applying modulation amplitude higher than the radical electron paramagnetic resonance linewidth. Data were gathered by applying four constant modulation amplitudes, where one was below 1/3 (Amod = 0.04 mT) of the radical linewidth (DeltaBpp = 0.14 mT). Three other modulation amplitude values were used in this experiment, leading to undermodulated (Amod < 1/3 DeltaBpp), partially overmodulated (Amod ~ 1/3 DeltaBpp) and fully overmodulated (Amod > > 1/3 DeltaBpp) projections. The advantages of an applied overmodulation condition were demonstrated in the study performed on a phantom containing four shapes of 1.25 mM water solution of 2, 2, 6, 6-tetramethyl-1-piperidinyloxyl. It was shown that even when the overmodulated reference spectrum was used in the deconvolution procedure, as well as the projection itself, the phantom shapes reconstructed as images directly correspond to those obtained in undermodulation conditions. It was shown that the best SNR of the reconstructed images is expected for the modulation amplitude close to 1/3 of the projection linewidth, which is defined as the distance from the first maximum to the last minimum of the gradient broadened spectrum. For higher modulation amplitude, the SNR of the reconstructed image is decreased, even if the SNR of the measured projection is increased. PMID- 26364567 TI - Self-healing multilayer polyelectrolyte composite film with chitosan and poly(acrylic acid). AB - If self-healing materials can be prepared via simple technology and methods using nontoxic materials, this would be a great step forward in the creation of environmentally friendly self-healing materials. In this paper, the specific structural parameters of the various hydrogen bonds between chitosan (CS) and polyacrylic acid (PAA) were calculated. Then, multilayer polyelectrolyte films were fabricated with CS and PAA based on layer-by-layer (LbL) self-assembly technology at different pH values. The possible influence of pH on the (CS/PAA) * 30 multilayer polyelectrolyte film was investigated. The results show that the interactions between CS and PAA, swelling capacity, microstructure, wettability, and self-healing ability are all governed by the pH of the CS solution. When the pH value of the CS solution is 3.0, the prepared multilayer polyelectrolyte film (CS3.0/PAA2.8) * 30 has fine-tuned interactions, a network-like structure, good swelling ability, good hydrophilicity, and excellent self-healing ability. This promises to greatly widen the future applications of environmentally friendly materials and bio-materials. PMID- 26364568 TI - Absolute Configuration Determination of Azulenyl Diols Isolated From Asymmetric Pinacol Coupling. AB - A convenient enantioselective approach for the pinacol coupling of 1 acetylazulene involving easily accessible (R)- or (S)-BINOLs as chiral additive is reported. This supposes the preformation of the chiral titanium-BINOL complex in 1:2 ratio and subsequent reduction with zinc when, 2,3-di(azulen-1-yl)butane 2,3-diol can be isolated in around 60% enantiomeric excess. The absolute configuration of the isolated enantiomers was assigned by comparison of the experimental and Boltzmann-weighted calculated VCD and ECD spectra and assigned as (+)-(2S;3S)-di(azulen-1-yl)butane-2,3-diol. Chirality 27:826-834, 2015. (c) 2015 Wiley Periodicals, Inc. PMID- 26364569 TI - Robot-assisted laparoendoscopic single-site inguinal lymphadenectomy: initial investigation in a cadaver model. PMID- 26364570 TI - Acute kidney injury: definition, diagnosis and epidemiology. AB - Acute kidney injury (AKI) is a common complication in hospitalized patients and great efforts by leading experts have been made in order to establish common definitions of AKI. The clinical use of these consensus definitions has led to a substantially improved understanding of AKI. In addition, the consensus definitions allow to compare AKI incidence and outcomes between different patient populations. As a result, it has become evident that AKI in the Western population represents a clinical syndrome with an incidence close to that of myocardial infarction. The aim of this review is to revisit the current concepts and definitions of AKI, to highlight its diagnosis, and to emphasize its epidemiological characteristics. Here, we will focus on the available literature reporting the epidemiology of AKI in critically ill patients. Sepsis, major surgery, and nephrotoxic drugs are the main causes of AKI in these patients, and its occurrence is associated with an increased risk for sustained chronic kidney injury. We also discuss the concept of renal angina as a possible future concept for improved clinical risk stratification to detect AKI. In this regard, we emphasize the importance of the use of novel biomarkers in the diagnosis of AKI, as they hold the potential to improve early diagnosis and prevention in the clinical setting. PMID- 26364571 TI - Prevention of infectious complications of percutaneous nephrolithotomy. AB - Infection and sepsis is a complication of percutaneous nephrolithotomy that can lead to morbidity, mortality, and increased costs. Herein we review the current relevant literature on the topic of prevention of sepsis after percutaneous nephrolithotomy. PMID- 26364573 TI - Europe in world regional perspective: formations of modernity and major historical transformations. AB - The paper seeks to present a world regional approach to the analysis of modernity and in doing so it also aims to make a contribution to comparative sociology and social theory. It is argued that world regions are the most suitable entry-point for comparing different socio-political constellations of our time, preferable to continents, civilizations and nation-states. However, a world regional foundation on its own is insufficient, due to the internal plurality and historically changing forms of world regions, and therefore needs to be accompanied by a concept that provides some degree of coherence within world regions and a tool for comparison with other world regions. The notion of modernity offers this level of generality while at the same time allowing for variety in its historical forms. Six main formations of modernity are identified, of which the European model was the first one and often a cultural reference for many other parts of the world. The thesis is that in the present day the most important developments are in the Asian and Latin American varieties, which unlike Europe are witnessing major historical transformation. Decisive in all of this is the question of democratization in the shaping of social imaginaries. Beginning with the problem of how to define the specificity of Europe, the paper provides an exploratory analysis of some of the salient considerations around a number of world regions, their formations of modernity, and the extent of major historical transformations in their present constitution. PMID- 26364572 TI - Immunoglobulin gene expression in umbilical cord blood-derived CD34+ hematopoietic stem/progenitor cells. AB - Recently, immunoglobulin (Ig) expression was reported in a variety of non-B lineage cells, including myeloid cells. We assessed whether hematopoietic stem/progenitor cells (HSC/HPCs) can express Ig. With Gene Expression Omnibus (GEO) microarray database analysis, we found that IGHM was expressed with the highest frequency and level in umbilical cord blood CD34(+) HSC/HPCs, followed by IGK@, IGHE, IGHD, IGHG1, and IGHA1, while IGL@ was nearly not expressed. Ig expression was further confirmed by molecular experiments and immunofluorescence. Moreover, HSC/HPCs-derived Ig displayed restricted/biased usages and VHDJH rearrangement patterns. These results suggest that Igs, especially IgM, may have a role in CD34(+) HSC/HPCs function. PMID- 26364574 TI - Methodological troubles as problems and phenomena: ethnomethodology and the question of 'method' in the social sciences. AB - Across the disciplinary frontiers of the social sciences, studies by social scientists treating their own investigative practices as sites of empirical inquiry have proliferated. Most of these studies have been retrospective, historical, after-the-fact reconstructions of social scientific studies mixing interview data with the (predominantly textual) traces that investigations leave behind. Observational studies of in situ work in social science research are, however, relatively scarce. Ethnomethodology was an early and prominent attempt to treat social science methodology as a topic for sociological investigations and, in this paper, we draw out what we see as its distinctive contribution: namely, a focus on troubles as features of the in situ, practical accomplishment of method, in particular, the way that research outcomes are shaped by the local practices of investigators in response to the troubles they encounter along the way. Based on two case studies, we distinguish methodological troubles as problems and methodological troubles as phenomena to be studied, and suggest the latter orientation provides an alternate starting point for addressing social scientists' investigative practices. PMID- 26364575 TI - Microstructures of economic action: talk, interaction and the bottom line. AB - This paper contributes to an expanding body of research that has analysed the interactional foundations of economic activity, and price determination, by quantifying the financial implications of different micro-interactional practices. Drawing on video recordings of naturalistic interaction the paper analyses a simple consumer choice, whether to pay one of two prices, the lower 'standard' price (L 8.00) or the higher 'gift aid' (L 8.80) price, to enter an arts institution. Utilizing resources from conversation analysis, the paper analyses different ways of posing this choice. It describes how, as interactional constraints tighten, standard prices become less socially desirable and customers increasingly 'volunteer' to pay the higher price. The paper contributes to sociological understandings of economic activity, demonstrating how simple one off choices, and prices, are accountably responsive to micro-interactional structures. PMID- 26364576 TI - Increasing inter-generational social mobility: is educational expansion the answer? AB - Reforms which increase the stock of education in a society have long been held by policy-makers as key to improving rates of intergenerational social mobility. Yet, despite the intuitive plausibility of this idea, the empirical evidence in support of an effect of educational expansion on social fluidity is both indirect and weak. In this paper we use the raising of the minimum school leaving age from 15 to 16 years in England and Wales in 1972 to estimate the effect of educational participation and qualification attainment on rates of intergenerational social class mobility. Because, in expectation, children born immediately before and after the policy was implemented are statistically exchangeable, the difference in the amount of education they received may be treated as exogenously determined. The exogenous nature of the additional education gain means that differences in rates of social mobility between cohorts affected by the reform can be treated as having been caused by the additional education. The data for the analysis come from the ONS Longitudinal Study, which links individual records from successive decennial censuses between 1971 and 2001. Our findings show that, although the reform resulted in an increase in educational attainment in the population as a whole and a weakening of the association between attainment and class origin, there was no reliably discernible increase in the rate of intergenerational social mobility. PMID- 26364577 TI - Direct light-induced polymerization of cobalt-based redox shuttles: an ultrafast way towards stable dye-sensitized solar cells. AB - The photopolymerization of Co(II)/Co(III) complexes for dye-sensitized solar cells (DSSCs) by means of a fast, inexpensive, in situ and inhibition-free process has been examined. We have succeeded in fabricating high-performance DSSCs able to retain a light-to-electricity power conversion efficiency exceeding 6.5% (8.5% at low intensity) after 1800 h of mixed (light on/off, temperature high/low) accelerated aging tests, thus revealing a possible way for the stabilization of these record-holding redox pairs. PMID- 26364578 TI - Zinc oxide nanoparticles induce lipoxygenase-mediated apoptosis and necrosis in human neuroblastoma SH-SY5Y cells. AB - Zinc oxide nanoparticles (ZnO NPs) are known to induce oxidative stress and modulate an inflammatory process in various cell types. Although the cytotoxic effects of ZnO NPs in various cell types have been evaluated, few neurotoxic surveys on ZnO NPs as well as rescue studies have been reported. This study was designed to examine the neurotoxic ZnO NP concentration according to exposure time and dose, and the mechanisms that underlie ZnO NP-induced neurotoxicity in the SH-SY5Y human neuroblastoma cell line. A significant reduction in neuronal viability as well as distinct morphological findings resulted from application of 15 MUM ZnO NPs. Apoptotic injury-as measured by annexin V and caspase 3/7 activities-was significantly elevated at 12 h and 24 h, but not 6 h, after ZnO NP exposure. However, electron microscopy revealed typical necrotic characteristics, such as swelling or loss of cell organelles and rupture of the cytosolic or nuclear membrane at 12 h and 24 h after ZnO NP exposure. In rescue studies, the lipoxygenase (LOX) inhibitor esculetin attenuated ZnO NP-induced neuronal injury. The elevation of PI3 kinase (PI3K) and p-Akt/Akt activities induced by ZnO NP was significantly decreased by esculetin or LY294002. Allopurinol, N-acetyl-l cysteine and alpha-tocopherol protected ZnO NP-induced cytotoxicity. Sodium nitroprusside (SNP)-induced neurotoxicity and ZnO NP-mediated NO overproduction were ameliorated by esculetin. Esculetin reduced the production of reactive oxygen species (ROS) and the depletion of antioxidant enzymes induced by ZnO NPs. The concentration of zinc from the dissolution of ZnO NPs increased in proportion to increases in the ZnO NPs concentration. These results suggest that ZnO NPs induce apoptosis via the PI3K/Akt/caspase-3/7 pathway and necrosis by LOX mediated ROS production elevation. PMID- 26364579 TI - Pressure ulcers induced by drug administration: A new concept and report of four cases in elderly patients. AB - Drug-induced akinesia is a potential cause of pressure ulcers. However, pressure ulcers that are caused by drug-induced akinesia are not considered an adverse drug reaction (ADR). We propose that drug-induced pressure ulcers (DIPU) are pressure ulcers that are caused by an external force that is experienced after drug administration, and we considered resolution of these ulcers after drug discontinuation to be a supportive finding. In this report, we reviewed the medical records of pressure ulcer cases from a 300-bed hospital. Among 148 patients, four patients with pressure ulcers met the criterion for DIPU. In these cases, the suspected DIPU were related to treatment with olanzapine, fluvoxamine, valproic acid, clotiazepam, triazolam and rilmazafone. These drugs were administrated to manage the patients' behavioral and psychological symptoms that accompanied dementia. The DIPU in these patients were categorized as stage IV according to the National Pressure Ulcer Advisory Panel criteria. Discontinuation of the causal drugs led to significant improvements or complete healing of the pressure ulcers, and the patients subsequently recovered their mobility. Therefore, we propose that DIPU are potential ADR that have been overlooked in clinical practice. Thus, recognition of DIPU as an ADR may be important in preventing and appropriately managing pressure ulcers among elderly patients. PMID- 26364580 TI - Surgical repair of the isolated incomplete median cleft lip. AB - Median cleft lip refers to a vertical cleft on the midline of the upper lip. It is a rare congenital craniofacial anomaly brought about by a fusion failure in the medial nasal prominence. A novel surgical approach to median cleft lips and their repair is reported herein, with reference to a clinical case. The patient had a cleft in the lower half of the upper lip. There were no other craniofacial anomalies in this patient other than the cleft. Within the framework of the patient's surgical treatment, a functional and cosmetically satisfactory result was achieved by performing a V-Y advancement flap on the columella base, Z-plasty in the vermillion zone, and Z pattern muscular tissue repair, without having to resort to any tissue excisions. PMID- 26364581 TI - Masitinib monotherapy in canine epitheliotropic lymphoma. AB - This study evaluated efficacy and side effects of masitinib in canine epitheliotropic lymphoma. Complete remission occurred in 2 of 10 dogs and lasted for median 85 days. Five dogs went into partial remission for median 60.5 days. Three pretreated dogs did not respond to therapy. Side effects occurred in six dogs and were mostly mild to moderate. Immunohistochemistry was available for eight dogs. KIT receptor was negative in all of them, six of eight lymphomas stained strongly positive for stem cell factor (SCF). platelet-derived growth factor (PDGF)-AA was weakly positive in two and negative in six. PDGF-BB was negative in four tumours, weakly positive in one and strongly positive in three. One was strongly positive for PDGF receptor (PDGFR)-beta, seven were negative for that receptor. Five showed strong expression of PDGFR-alpha, two showed weak expression, one was negative. In conclusion, masitinib is effective in treating canine epitheliotropic lymphoma. But its effects are most likely not generated through the KIT receptor. PMID- 26364582 TI - Direct Methylation of Amines with Carbon Dioxide and Molecular Hydrogen using Supported Gold Catalysts. AB - The N-methylation of amines with CO2 and H2 is an important step in the synthesis of bioactive compounds and chemical intermediates. The first heterogeneous Au catalyst is reported for this methylation reaction with good to excellent yields. The average turnover frequency (TOF) based on surface Au atoms is 45 h(-1) , which is the highest TOF value ever reported for the methylation of aniline with CO2 and H2 . Furthermore, the catalyst is tolerant toward a variety of amines, which includes aromatic, aliphatic, secondary, and primary amines. Preliminary mechanistic studies suggest that the N-alkyl formamide might be an intermediate in the N-methylation of amine process. Moreover, through a one-pot process, it is possible to convert primary amines, aldehydes, and CO2 into unsymmetrical tertiary amines with H2 as a reductant in the presence of the Au catalyst. PMID- 26364583 TI - Sipa1l3/SPAR3 is targeted to postsynaptic specializations and interacts with the Fezzin ProSAPiP1/Lzts3. AB - Rap GTPase-activating proteins (RapGAPs) are essential for synaptic function as they tightly regulate synaptic Rap signaling. Among the most abundant synaptic RapGAPs in brain are the Spine-associated RapGAPs (SPARs) Sipa1l1/SPAR and Sipa1l2/SPAR2, whereas nothing has been reported on Sipa1l3/SPAR3. In this study, we show that Sipa1l3/SPAR3 is conserved across species, has a distinct expression pattern in the developing rat brain and is localized at excitatory postsynapses. We further demonstrate that the Sipa1l3/SPAR3 C-terminus is required for postsynaptic targeting and represents an interaction module for Fezzins such as ProSAPiP1/Lzts3, a binding partner of the postsynaptic scaffold protein Shank3. Taken together, our data imply that Sipa1l3/SPAR3 is a hitherto unknown synaptic RapGAP, which is targeted to postsynaptic specializations and interacts with Fezzins. Spine-associated RapGAPs (SPARs) are essential modulators of synaptic signaling. Our study is the first to characterize the SPAR family member Sipa1l3/SPAR3 in neuronal tissue. We show that Sipa1l3/SPAR3 is conserved across species, has a distinct expression pattern in brain and is localized to excitatory postsynapses via its C-terminus, which represents an interaction module for other postsynaptic proteins including the Fezzin ProSAPiP1/Lzts3. PMID- 26364584 TI - Carnosine reverses the aging-induced down regulation of brain regional serotonergic system. AB - The purpose of the present investigation was to study the role of carnosine, an endogenous dipeptide biomolecule, on brain regional (cerebral cortex, hippocampus, hypothalamus and pons-medulla) serotonergic system during aging. Results showed an aging-induced brain region specific significant (a) increase in Trp (except cerebral cortex) and their 5-HIAA steady state level with an increase in their 5-HIAA accumulation and declination, (b) decrease in their both 5-HT steady state level and 5-HT accumulation (except cerebral cortex). A significant decrease in brain regional 5-HT/Trp ratio (except cerebral cortex) and increase in 5-HIAA/5-HT ratio were also observed during aging. Carnosine at lower dosages (0.5-1.0MUg/Kg/day, i.t. for 21 consecutive days) didn't produce any significant response in any of the brain regions, but higher dosages (2.0-2.5MUg/Kg/day, i.t. for 21 consecutive days) showed a significant response on those aging-induced brain regional serotonergic parameters. The treatment with carnosine (2.0MUg/Kg/day, i.t. for 21 consecutive days), attenuated these brain regional aging-induced serotonergic parameters and restored towards their basal levels that observed in 4 months young control rats. These results suggest that carnosine attenuates and restores the aging-induced brain regional down regulation of serotonergic system towards that observed in young rats' brain regions. PMID- 26364585 TI - Three-dimensional N,B-doped graphene aerogel as a synergistically enhanced metal free catalyst for the oxygen reduction reaction. AB - Here, a novel N,B-doped graphene aerogel, abbreviated as N,B-GA, was obtained via a two-step approach and served as a metal-free catalyst for the oxygen reduction reaction (ORR). This two-step method involved a hydrothermal reaction and a pyrolysis procedure, guaranteeing the efficient insertion of the heteroatoms. The resulting three-dimensional (3D) N,B-GA obtained at pyrolysis temperature of 1000 degrees C exhibited outstanding catalytic activity for the oxygen reduction reaction (ORR), comparable to that of Pt/C. In addition, the catalytic activity of this 3D N,B-GA was obviously better than that of the nitrogen-doped graphene aerogel (N-GA) and boron-doped graphene aerogel (B-GA) in terms of the onset potential, half-wave potential and diffusion limiting current density. The superior catalytic reactivity arises from the synergistic coupling of the B and N dopants within the graphene domains. PMID- 26364586 TI - Nanophotonic coherent light-matter interfaces based on rare-earth-doped crystals. AB - Quantum light-matter interfaces connecting stationary qubits to photons will enable optical networks for quantum communications, precise global time keeping, photon switching and studies of fundamental physics. Rare-earth-ion-doped crystals are state-of-the-art materials for optical quantum memories and quantum transducers between optical photons, microwave photons and spin waves. Here we demonstrate coupling of an ensemble of neodymium rare-earth-ions to photonic nanocavities fabricated in the yttrium orthosilicate host crystal. Cavity quantum electrodynamics effects including Purcell enhancement (F=42) and dipole-induced transparency are observed on the highly coherent (4)I(9/2)-(4)F(3/2) optical transition. Fluctuations in the cavity transmission due to statistical fine structure of the atomic density are measured, indicating operation at the quantum level. Coherent optical control of cavity-coupled rare-earth ions is performed via photon echoes. Long optical coherence times (T2~100 MUs) and small inhomogeneous broadening are measured for the cavity-coupled rare-earth ions, thus demonstrating their potential for on-chip scalable quantum light-matter interfaces. PMID- 26364587 TI - The Neuroprotective Role of Insulin Against MPP(+) -Induced Parkinson's Disease in Differentiated SH-SY5Y Cells. AB - Parkinson's disease (PD) is a common chronic neurodegenerative disorder associated with aging that primarily caused by the death of dopaminergic neurons in the substantia nigra pars compacta (SN). Retinoic acid (RA)-differentiated human neuroblastoma SH-SY5Y cells (SH-SY5Y+RA) have been broadly utilized in studies of mechanisms of the pathogenesis underlying 1-Methyl-4-phenyl pyridinium (MPP(+))-induced PD models. Here, we investigated the neuroprotective mechanisms of insulin on MPP(+)-induced neurotoxicity on SH-SY5Y+RA cells. Recent studies suggest that insulin has a protective effect against oxidative stress but not been elucidated for PD. In this study, pretreatment of insulin prevented the cell death in a dose dependent manner and lowered nitric oxide (NO) release, reactive oxygen species (ROS), and calcium ion (Ca(2+)) influx induced by MPP(+). Insulin also elevated tyrosine hydroxylase (TH) and insulin signaling pathways in dopaminergic neuron through activating PI3K/Akt/GSK-3 survival pathways which in turn inhibits MPP(+)-induced iNOS and ERK activation, and Bax to Bcl-2 ratio. These results suggest that insulin has a protective effect on MPP(+) neurotoxicity in SH-SY5Y+RA cells. PMID- 26364588 TI - Effect of glove occlusion on the skin barrier. AB - Wet work tasks are the most common exposures leading to occupational irritant contact dermatitis. Use of liquid-proof gloves is recommended when performing wet work, however, gloves may also contribute to impairment of the skin barrier and development of irritant contact dermatitis. The aim of this study is to review the literature on the effects of glove occlusion on skin barrier function. The PubMed database was searched up to 1 February 2015 for articles on the association between glove occlusion and skin barrier function, including human studies only and in English. Only experimental studies including assessment of the skin barrier function were included in the data analysis. Thirteen articles were identified, 8 with focus on occlusion alone, 7 with focus on occlusion in combination with irritant exposure (some overlapping), and 2 field studies. In conclusion, data from the literature showed that the negative effect of occlusion in itself is limited, and that only extensive and long-term occlusion will cause barrier impairment. However, studies investigating combined effect of occlusion and exposure to soaps/detergents indicate that occlusion significantly enhances the skin barrier damage caused by detergents/soaps in a dose-response fashion. PMID- 26364589 TI - Work ability, age and intention to leave aged care work. AB - AIM: To describe the work ability of mature age women workers in Australia's aged care sector, and to explore the relationship between ageing, work ability and intention to leave. METHOD: Logistic regression techniques were applied to a sample of 2721 responses to a survey of mature age women workers in the aged care sector. RESULTS: Mature age women working in the Australian aged care sector have relatively high levels of work ability by international standards. Furthermore, their work ability remains high in their 50s and 60s, in contrast to some prevailing stereotypes. However, work ability is a key determinant of intention to leave in key occupational groups. CONCLUSION: Our findings challenge some prevailing stereotypes about the work ability of mature age workers. However, they lend support for the development of retention strategies, which incorporate programs that target low work ability. PMID- 26364590 TI - Practical guide for calculating and representing biased signaling by GPCR ligands: A stepwise approach. AB - Signaling bias makes reference to the capacity of G-protein coupled receptor (GPCR) ligands to direct pharmacological stimuli to a subset of effectors among all of those controlled by the receptor. This new signaling modality has added texture to the classical notion of efficacy. In doing so, it has opened new avenues for the development of therapeutic GPCR ligands that specifically modulate signals underlying desired effects while sparing those that support undesired drug actions. Essential to taking advantage of this texture is the ability to identify, quantify and represent bias in a reliable and intuitive manner that ensures comparison among ligands. Here, we present a practical guide on how the operational model may be used to evaluate ligand efficiency to induce different responses, how differences in response may be used to estimate bias and how quantitative information derived from this analysis may be graphically represented to recreate a drug's unique signaling footprint. The approach used is discussed in terms of data interpretation and limitations that may influence the conclusions drawn from the analysis. PMID- 26364591 TI - Differentiation of human pluripotent stem cells into Medial Ganglionic Eminence vs. Caudal Ganglionic Eminence cells. AB - Human pluripotent stem cells (PSCs) represent an opportunity to study human development in vitro, to model diseases in a dish, to screen drugs as well as to provide an unlimited and ethically unimpeded source of therapeutic cells. Cortical GABAergic interneurons, which are generated from Medial Ganglionic Eminence (MGE) cells and Caudal Ganglionic Eminence (CGE) cells during embryonic development, regulate cortical neural networks by providing inhibitory inputs. Their malfunction, resulting in failure to intricately regulate neural circuit balance, has been implicated in brain diseases, such as schizophrenia, autism and epilepsy. In this study, using combinatorial and temporal modulation of developmentally relevant dorsoventral and rostrocaudal signaling pathways, we efficiently generated MGE cells vs. CGE cells from human PSCs, which predominantly generate Parvalbumin-expressing or Somatostatin-expressing interneurons vs. Calretinin-expressing interneurons, respectively. Efficient generation of specific differentiated progenies of hPSCs as shown in this study will be a pivotal step to realize the full potential of hPSCs for regenerative medicine, developmental studies, disease modeling, bioassay, and drug screening. PMID- 26364592 TI - A highly conserved NF-kappaB-responsive enhancer is critical for thymic expression of Aire in mice. AB - Autoimmune regulator (Aire) has a unique expression pattern in thymic medullary epithelial cells (mTECs), in which it plays a critical role in the activation of tissue-specific antigens. The expression of Aire in mTECs is activated by receptor activator of nuclear factor kappaB (RANK) signaling; however, the molecular mechanism behind this activation is unknown. Here, we characterize a conserved noncoding sequence 1 (CNS1) containing two NF-kappaB binding sites upstream of the Aire coding region. We show that CNS1-deficient mice lack thymic expression of Aire and share several features of Aire-knockout mice, including downregulation of Aire-dependent genes, impaired terminal differentiation of the mTEC population, and reduced production of thymic Treg cells. In addition, we show that CNS1 is indispensable for RANK-induced Aire expression and that CNS1 is activated by NF-kappaB pathway complexes containing RelA. Together, our results indicate that CNS1 is a critical link between RANK signaling, NF-kappaB activation, and thymic expression of Aire. PMID- 26364593 TI - Effect of smoking cessation for 1 year on periodontal biomarkers in gingival crevicular fluid. AB - BACKGROUND AND OBJECTIVE: The aim of this 12 mo prospective study was to assess the effect of smoking cessation on periodontal tissue without periodontal intervention, using matrix metalloproteinase (MMP)-8, MMP-9 and interleukin (IL) 1beta in gingival crevicular fluid, and nicotine and cotinine in saliva. MATERIAL AND METHODS: Of the 122 male smokers enrolled in a smoking cessation clinic, 11 quitters, nine non-quitters, six oscillators and 13 non-smokers participated in all experiments done at follow-up week 2, and follow-up months 2, 4, 6 and 12. The following were measured: gingival index; dental plaque index and sites of 3.5 mm < probing depth < 5.5 mm using a WHO probe for the full mouth; amounts of MMP 8, MMP-9 and IL-1beta in gingival crevicular fluid of the upper anterior teeth area using enzyme-linked immunosorbent assay; and concentrations of nicotine, cotinine and hydroxycotinine in saliva using high-performance liquid chromatography-tandem mass spectrometry. RESULTS: No significant differences in MMP-8 and MMP-9 in gingival crevicular fluid were detected between smokers, quit smokers, oscillators and non-smokers for 1 year. Only the amount of IL-1beta showed that smokers (90.14 +/- 65.32 pg/mL) had a significantly higher value compared with non-smokers (37.70 +/- 40.90 pg/mL), quit-smokers (32.11 +/- 40.50 pg/mL) and oscillators (11.90 +/- 12.46 pg/mL) at 2 mo follow-up (p = 0.007). IL 1beta had a positive correlation with nicotine (r = 0.351) and the cotinine (r = 0.376), nicotine (r = 0.492) and hydroxycotinine (r = 0.358), and hydroxycotinine (r = 0.413) levels at 2 wk and 4 and 6 mo follow-up, respectively. CONCLUSIONS: This 1-year prospective smoking cessation study without nonsurgical periodontal therapy shows IL-1beta in gingival crevicular fluid could have a positive relationship with the nicotine and cotinine levels in saliva. PMID- 26364594 TI - Insights into bread melanoidins: fate in the upper digestive tract and impact on the gut microbiota using in vitro systems. AB - Bread melanoidins are heterogeneous, nitrogen-containing, brown macromolecules generated during the last stages of the Maillard reaction in bread. The aim of this study was to investigate the impact and fate of these bread melanoidins in the human gastrointestinal tract using in vitro systems. Batch systems as well as the TNO gastrointestinal tract were used for studying the digestion of various bread samples. These samples included bread crumb, bread crust and two bread crust-simulating models: a fiber-free model (gluten, starch and glucose heated together) and its control, free of Maillard reaction products (gluten heated separately than starch and glucose). Furthermore, the impact of these two bread crust-simulating models on the gut microbiota was assessed using a static anaerobic batch system. Bread melanoidins from bread crust and its model were shown to be partially digested by amylases and proteases, suggesting that these melanoidins have peptidic as well as glycosidic bonds in their skeleton. The impact of bread melanoidins from the bread-crust-simulating models and their digestion products on the gut microbiota revealed an individual-dependent response for most flora except for enterobacteria. This flora decreased by -22%, 48% & -100% depending on the individual. Thus, bread melanoidins seem to exert an anti-inflammatory effect by inhibiting enterobacteria. PMID- 26364595 TI - hPso4/hPrp19: a critical component of DNA repair and DNA damage checkpoint complexes. AB - Genome integrity is vital to cellular homeostasis and its forfeiture is linked to deleterious consequences-cancer, immunodeficiency, genetic disorders and premature aging. The human ubiquitin ligase Pso4/Prp19 has emerged as a critical component of multiple DNA damage response (DDR) signaling networks. It not only senses DNA damage, binds double-stranded DNA in a sequence-independent manner, facilitates processing of damaged DNA, promotes DNA end joining, regulates replication protein A (RPA2) phosphorylation and ubiquitination at damaged DNA, but also regulates RNA splicing and mitotic spindle formation in its integral capacity as a scaffold for a multimeric core complex. Accordingly, by virtue of its regulatory and structural interactions with key proteins critical for genome integrity-DNA double-strand break (DSB) repair, DNA interstrand crosslink repair, repair of stalled replication forks and DNA end joining-it fills a unique niche in restoring genomic integrity after multiple types of DNA damage and thus has a vital role in maintaining chromatin integrity and cellular functions. These properties may underlie its ability to thwart replicative senescence and, not surprisingly, have been linked to the self-renewal and colony-forming ability of murine hematopoietic stem cells. This review highlights recent advances in hPso4 research that provides a fascinating glimpse into the pleiotropic activities of a ubiquitously expressed multifunctional E3 ubiquitin ligase. PMID- 26364596 TI - Molecular basis underlying resistance to Mps1/TTK inhibitors. AB - Mps1/TTK is a dual-specificity kinase, with an essential role in mitotic checkpoint signaling, which has emerged as a potential target in cancer therapy. Several Mps1/TTK small-molecule inhibitors have been described that exhibit promising activity in cell culture and xenograft models. Here, we investigated whether cancer cells can develop resistance to these drugs. To this end, we treated various cancer cell lines with sublethal concentrations of a potent Mps1/TTK inhibitor in order to isolate inhibitor-resistant monoclonal cell lines. We identified four point mutations in the catalytic domain of Mps1/TTK that gave rise to inhibitor resistance but retained wild-type catalytic activity. Interestingly, cross-resistance of the identified mutations to other Mps1/TTK inhibitors is limited. Our studies predict that Mps1/TTK inhibitor-resistant tumor cells can arise through the acquisition of mutations in the adenosine triphosphate-binding pocket of the kinase that prevent stable binding of the inhibitors. In addition, our results suggest that combinations of inhibitors could be used to prevent acquisition of drug resistance. Interestingly, cross resistance seems nonspecific for inhibitor scaffolds, a notion that can be exploited in future drug design to evict possible resistance mutations during clinical treatment. PMID- 26364597 TI - RUNX3 is a novel negative regulator of oncogenic TEAD-YAP complex in gastric cancer. AB - Runt-related transcription factor 3 (RUNX3) is a well-documented tumour suppressor that is frequently inactivated in gastric cancer. Here, we define a novel mechanism by which RUNX3 exerts its tumour suppressor activity involving the TEAD-YAP complex, a potent positive regulator of proliferative genes. We report that the TEAD-YAP complex is not only frequently hyperactivated in liver and breast cancer, but also confers a strong oncogenic activity in gastric epithelial cells. The increased expression of TEAD-YAP in tumour tissues significantly correlates with poorer overall survival of gastric cancer patients. Strikingly, RUNX3 physically interacts with the N-terminal region of TEAD through its Runt domain. This interaction markedly reduces the DNA-binding ability of TEAD that attenuates the downstream signalling of TEAD-YAP complex. Mutation of RUNX3 at Arginine 122 to Cysteine, which was previously identified in gastric cancer, impairs the interaction between RUNX3 and TEAD. Our data reveal that RUNX3 acts as a tumour suppressor by negatively regulating the TEAD-YAP oncogenic complex in gastric carcinogenesis. PMID- 26364598 TI - Breast cancer dissemination promoted by a neuregulin-collagenase 3 signalling node. AB - Advances in the treatment of breast cancer have resulted in increased survival. However, in the metastatic setting, the disease remains incurable. Therefore, understanding of the mechanisms that promote dissemination of breast cancer cells may favor the development of novel therapeutic strategies to fight those tumors. Here, we show that the ErbB ligands, Neuregulins (NRGs), promote metastatic dissemination of breast cancer cells by switching on a kinase-metalloproteinase network. Clinicopathological analyses demonstrated that NRG expression in breast tumors associated to lymph node invasion and poor patient outcome. Preclinical in vivo analyses showed that NRG expression favored in situ tumor growth, local spreading and metastatic dissemination. Genomic, biochemical and functional studies identified matrix metalloproteinases, particularly stromelysin 2 and collagenase 3, as key mediators of the NRG-induced dissemination properties of breast cancer cells. Mechanistic analyses demonstrated that NRG augmented metalloproteinase expression through a route controlled by ERK1/2 kinases. ERK1/2 increased collagenase 3 expression by controlling the activity of an SBF1-related transcription factor. In conclusion, we describe a pathway linked to breast cancer dissemination. The clinical availability of agents that target some of the components of this signalling pathway suggests that patients with tumors fed by NRGs or other factors able to activate the ERK-Collagenase 3 route may benefit from agents that act on that signalling axis. PMID- 26364599 TI - Targeting MET and AXL overcomes resistance to sunitinib therapy in renal cell carcinoma. AB - Antiangiogenic therapy resistance occurs frequently in patients with metastatic renal cell carcinoma (RCC). The purpose of this study was to understand the mechanism of resistance to sunitinib, an antiangiogenic small molecule, and to exploit this mechanism therapeutically. We hypothesized that sunitinib-induced upregulation of the prometastatic MET and AXL receptors is associated with resistance to sunitinib and with more aggressive tumor behavior. In the present study, tissue microarrays containing sunitinib-treated and untreated RCC tissues were stained with MET and AXL antibodies. The low malignant RCC cell line 786-O was chronically treated with sunitinib and assayed for AXL, MET, epithelial mesenchymal transition (EMT) protein expression and activation. Co-culture experiments were used to examine the effect of sunitinib pretreatment on endothelial cell growth. The effects of AXL and MET were evaluated in various cell-based models by short hairpin RNA or inhibition by cabozantinib, the multi tyrosine kinases inhibitor that targets vascular endothelial growth factor receptor, MET and AXL. Xenograft mouse models tested the ability of cabozantinib to rescue sunitinib resistance. We demonstrated that increased AXL and MET expression was associated with inferior clinical outcome in patients. Chronic sunitinib treatment of RCC cell lines activated both AXL and MET, induced EMT associated gene expression changes, including upregulation of Snail and beta catenin, and increased cell migration and invasion. Pretreatment with sunitinib enhanced angiogenesis in 786-0/human umbilical vein endothelial cell co-culture models. The suppression of AXL or MET expression and the inhibition of AXL and MET activation using cabozantinib both impaired chronic sunitinib treatment induced prometastatic behavior in cell culture and rescued acquired resistance to sunitinib in xenograft models. In summary, chronic sunitinib treatment induces the activation of AXL and MET signaling and promotes prometastatic behavior and angiogenesis. The inhibition of AXL and MET activity may overcome resistance induced by prolonged sunitinib therapy in metastatic RCC. PMID- 26364600 TI - NF-kB2 induces senescence bypass in melanoma via a direct transcriptional activation of EZH2. AB - Enhancer of Zeste homologue 2 (EZH2) belongs to the polycomb repressive complex 2 and catalyzes the methylation of histone H3 lysine 27. These pivotal epigenetic marks are altered in many cancers, including melanoma, as a result of EZH2 overexpression. Here, we show that the non-canonical-NF-kB pathway accounts for most of the NF-kB activity in melanoma cells, in contrast to non-cancer cells. We identify the non-canonical-NF-kB pathway as a key regulator of EZH2 expression in melanoma. We show a striking correlation between NF-kB2 and EZH2 expression in human melanoma metastases. We demonstrate that inhibition of the non-canonical NF kB pathway by targeting NF-kB2/p52 or the upstream kinase NIK restores the senescence program in melanoma cells through the decrease of EZH2. On the contrary, the overexpression of NF-kB2/p52 in normal human melanocytes prevents stress- and oncogene-induced senescence. Finally, we show in mouse models that the inhibition of the non-canonical NF-kB pathway restores senescence and induces a dramatic reduction in tumor growth compared with controls, thus providing potential drug targets for the re-induction of senescence in melanoma and other cancers where EZH2 is overexpressed. PMID- 26364601 TI - Structural centrosome aberrations favor proliferation by abrogating microtubule dependent tissue integrity of breast epithelial mammospheres. AB - Structural centrosome aberrations are frequently observed in early stage carcinomas, but their role in malignant transformation is poorly understood. Here, we examined the impact of overexpression of Ninein-like protein (Nlp) on the architecture of polarized epithelia in three-dimensional mammospheres. When Nlp was overexpressed to levels resembling those seen in human tumors, it formed striking centrosome-related bodies (CRBs), which sequestered Ninein and affected the kinetics of microtubule (MT) nucleation and release. In turn, the profound reorganization of the MT cytoskeleton resulted in mislocalization of several adhesion and junction proteins as well as the tumor suppressor Scribble, resulting in the disruption of epithelial polarity, cell-cell interactions and mammosphere architecture. Remarkably, cells harboring Nlp-CRBs displayed an enhanced proliferative response to epidermal growth factor. These results demonstrate that structural centrosome aberrations cause not only the disruption of epithelial polarity but also favor overproliferation, two phenotypes typically associated with human carcinomas. PMID- 26364603 TI - Neddylation controls basal MKK7 kinase activity in breast cancer cells. AB - The c-Jun NH2-terminal protein kinase (JNK) pathway has been implicated in mammary tumor development. However, the molecular mechanisms regulating JNK activity in breast cancer cells remain unclear. Here, we report that the inhibition of ubiquitination-like post-translational modification neddylation through different strategies results in enhanced basal JNK phosphorylation in human breast cancer cells. The upregulation of basal JNK phosphorylation upon neddylation inhibition is independent of the deneddylation of Cullins, the well characterized neddylation substrates. Since augmented basal JNK phosphorylation via ectopic MKK7 expression impedes proliferation and the epithelial-to mesenchymal transition (EMT) phenotype, the neddylation system might contribute to mammary tumor development partially through limiting basal JNK phosphorylation. Further exploration reveals that MKK7, a JNK-specific MAP2K, undergoes neddylation in human breast cancer cells. MKK7 co-precipitates with a fragment of Ran-binding protein 2 (RanBP2), a large multimodular and pleiotropic protein that has been recognized as a SUMO E3 ligase. Knockdown of RanBP2 attenuates MKK7 neddylation and augments basal JNK phosphorylation without affecting the neddylation of Cullins, whereas ectopic expression of a RanBP2 fragment possessing SUMO E3 activity (RanBP2DeltaFG) manifests the opposite effects. In vitro neddylation assays confirm that RanBP2DeltaFG works as the neddylation E3 ligase for MKK7. The basal kinase activity of endogenous MKK7 increases upon RanBP2 knockdown but decreases upon the ectopic expression of RanBP2DeltaFG. Furthermore, purified MKK7 shows reduced basal kinase activity after in vitro neddylation by RanBP2DeltaFG. Consistently, RanBP2 knockdown leads to reduced proliferation and impaired EMT phenotype in human breast cancer cells and the effects of RanBP2 knockdown are reversed by simultaneous MKK7 knockdown. Taken together, our data suggest that MKK7 undergoes neddylation in human breast cancer cells, which limits its basal kinase activity. PMID- 26364602 TI - YAP induces high-grade serous carcinoma in fallopian tube secretory epithelial cells. AB - Accumulating evidence indicates that ovarian high-grade serous carcinoma (HGSC) originates from fallopian tube secretory epithelial cells (FTSECs). However, the molecular mechanisms underlying the initiation and progression of HGSC derived from FTSECs remains unclear. In this study, we found that the Hippo/Yes associated protein (YAP) signaling pathway has a critical role in the initiation and progression of fallopian tube and ovarian HGSC. Importantly, YAP was overexpressed in inflammatory and cancerous fallopian tube tissues. Further, overexpression of wild-type YAP, or constitutively active YAP in immortalized FTSECs, induced cell proliferation, migration, colony formation and tumorigenesis. Moreover, the Hippo/YAP and the fibroblast growth factor (FGF) signaling pathways formed an autocrine/paracrine-positive feedback loop to drive the progression of the FTSEC-derived HGSC. Evidence in this study strongly suggests that combined therapy with inhibitors of YAP (such as verteporfin) and FGF receptors (such as BGJ398) can provide a novel therapeutic strategy to treat fallopian tube and ovarian HGSC. PMID- 26364604 TI - LZTFL1 suppresses lung tumorigenesis by maintaining differentiation of lung epithelial cells. AB - Lung cancer is the leading cause of cancer-related death in the United States, and metastatic behavior is largely responsible for this mortality. Mutations in multiple 'driver' oncogenes and tumor suppressors are known to contribute to the lung tumorigenesis and in some cases represent therapeutic targets. Leucine Zipper Transcription Factor-like 1 (LZTFL1) is located in the chromosome region 3p21.3 where allelic loss and genetic alterations occur early and frequently in lung cancers. Previously, we found that LZTFL1 is downregulated in epithelial tumors, including lung cancer, and functions as a tumor suppressor in gastric cancers. However, the functional role of LZTFL1 in lung oncogenesis is undefined. We show here that downregulation of LZTFL1 expression in non-small cell lung cancer is associated with recurrence and poor survival, whereas re-expression of LZTFL1 in lung tumor cells inhibited extravasation/colonization of circulating tumor cells to the lung and inhibited tumor growth in vivo. Mechanistically, we found that LZTFL1 is expressed in ciliated human bronchial epithelial cells (HBECs) and its expression correlates with HBEC differentiation. LZTFL1 inhibits transforming growth factor beta-activated mitogen-activated protein kinase and hedgehog signaling. Alteration of intracellular levels of LZTFL1 resulted in changes of expression of genes associated with epithelial-to-mesenchymal transition (EMT). We conclude that LZTFL1 inhibits lung tumorigenesis, possibly by maintaining epithelial cell differentiation and/or inhibition of signalings that lead to EMT and suggest that reactivation of LZTFL1 expression in tumor cells may be a novel lung cancer therapeutic approach. PMID- 26364605 TI - Mice deficient in Muc4 are resistant to experimental colitis and colitis associated colorectal cancer. AB - MUC4, a large transmembrane mucin normally expressed in the small and large intestine, is differentially expressed during inflammatory and malignant conditions of the colon. However, the expression pattern and the role of MUC4 in colitis and colorectal cancer (CRC) are inconclusive. Therefore, the aim of this study was to understand the role of Muc4 during inflammatory and malignant conditions of the colon. Here, we generated Muc4(-/-) mice and addressed its role in colitis and colitis-associated CRC using dextran sodium sulfate (DSS) and azoxymethane (AOM)-DSS experimental models, respectively. Muc4(-/-) mice were viable, fertile with no apparent defects. Muc4(-/-) mice displayed increased resistance to DSS-induced colitis compared with wild-type (WT) littermates that was evaluated by survival rate, body weight loss, diarrhea and fecal blood score, and histological score. Reduced infiltration of inflammatory cells, that is, CD3(+) lymphocytes and F4/80(+) macrophages was observed in the inflamed mucosa along with reduction in the mRNA levels of inflammatory cytokines interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha and anti-microbial genes Lysozyme M and SLPI in the colon of Muc4(-/-) mice compared with WT littermates. Compensatory upregulation of Muc2 and Muc3 mucins under basal and DSS treatment conditions partly explains the resistance observed in Muc4(-/-) mice. Accordingly, Muc4(-/-) mice exhibited significantly reduced tumor burden compared with WT mice assessed in a colitis-induced tumor model using AOM/DSS. An increased percentage of Ki67(+) nuclei was observed in the tumors from WT compared with Muc4(-/-) mice suggesting Muc4 to be critical in intestinal cell proliferation during tumorigenesis. Taken together, we conclusively demonstrate for the first time the role of Muc4 in driving intestinal inflammation and inflammation-associated tumorigenesis using a novel Muc4(-/-) mouse model. PMID- 26364606 TI - Stamping out RAF and MEK1/2 to inhibit the ERK1/2 pathway: an emerging threat to anticancer therapy. AB - The RAS-RAF-MEK1/2-ERK1/2 pathway is a key signal transduction pathway in the cells. Critically, it remains constitutively active in approximately 30% of human cancers, having key roles in cancer development, maintenance and progression, while being responsible for poorer prognosis and drug resistance. Consequently, the inhibition of this pathway has been the subject of intense research for >25 years. The advent of better patient screening techniques has increasingly shown that upstream regulators like RAS and RAF remain persistently mutated in many cancer types. These gain-of-function mutations, such as KRAS-4B(G12V/G13D/Q61K), NRAS(Q61L/Q61R) or BRAF(V600E), lead to tremendous increase in their activities, resulting in constitutively active extracellular signal-regulated kinase 1/2 (ERK1/2). They were not efficiently targeted by the first-generation inhibitors such as Lonafarnib or Sorafenib, which were essentially broad spectrum inhibitors targeting pan-RAS and pan-RAF, respectively. This triggered the development of the second-generation inhibitors selective against the mutated proteins. Second generation inhibitors such as Vemurafenib (Zelboraf) and Dabrafenib (Tafinlar) targeting BRAF(V600E), Trametinib (Mekinist) targeting MEK1/2 and the first generation pan-RAF inhibitor Sorafenib (Nexavar) have already been approved for treating renal, hepatocellular, thyroid cancers and BRAF(V600E/K) harboring metastatic melanoma. Others against RAF and MEK1/2 are presently undergoing clinical trials. Their success would depend on the better understanding of the acquired resistance mechanisms to these drugs in the cancer cells and the identification of predictive biomarkers for the proper administration of suitable inhibitor(s). PMID- 26364607 TI - Copy number variations of HLA-I and activation of NKp30 pathway determine the sensitivity of gastric cancer cells to the cytotoxicity of natural killer cells. AB - Nude mice are important in vivo model for characterization of cell malignancy behavior; however, many cancer cells fail to form tumors in it. Understanding this defective mechanism may provide novel insights into tumorigenesis and how tumor cells escape innate immunity. Whole-genome sequencing was conducted on two gastric cancer (GC) cells, BGC823 and AGS, which do and do not form tumors in nude mice, to identify their genomic differences relevant to natural killer (NK) cells. We found that the tumorigenic capacity of human GC cell lines was dependent on the recruitment and activation of NK cells in xenograft tumors. We used whole-genome sequence (WGS) on GC cell lines to identify potential genes controlling susceptibility to NK-mediated killing. The tumorigenic cell line BGC823 expressed high levels of HLA-I because of copy gain and was resistant to NK cell killing. In contrast, another cell line AGS expressing low levels of HLA I with activated NKp30/MAPK/IL-12 (interleukin-12) or IL-2 (interleukin-2) pathway was susceptible to NK lysis. Treatment of tumor bearing mice with systemic administration of IL-12 in combination with intratumor injection of anti HLA-I antibody significantly increased NK cell recruitment into xenograft tumors, which became sensitive to NK killing, resulting in reduced tumor progression. In human GC specimens, decreased HLA-I expression and increased NK cells surrounding tumor cells were correlated with decreased metastasis potential and better prognosis of patients. Our results provide a mechanistic basis for GC cells to escape NK lysis and a promising prospect of NK immunotherapy for GC cells. PMID- 26364608 TI - Comprehensive proteomic profiling identifies the androgen receptor axis and other signaling pathways as targets of microRNAs suppressed in metastatic prostate cancer. AB - MicroRNAs are important epigenetic regulators of protein expression by triggering degradation of target mRNAs and/or inhibiting their translation. Dysregulation of microRNA expression has been reported in several cancers, including prostate cancer (PC). We comprehensively characterized the proteomic footprint of a panel of 12 microRNAs that are potently suppressed in metastatic PC (SiM-miRNAs: miR-1, miR-133a, miR-133b, miR-135a, miR-143-3p, miR-145-3p, miR-205, miR-221-3p, miR 221-5p, miR-222-3p, miR-24-1-5p, and miR-31) using reverse-phase proteomic arrays. Re-expression of these SiM-miRNAs in PC cells suppressed cell proliferation and targeted key oncogenic pathways, including cell cycle, apoptosis, Akt/mammalian target of rapamycin signaling, metastasis and the androgen receptor (AR) axis. However, only 12%, at most, of these observed protein expression changes could be explained by predicted direct binding of miRNAs to corresponding mRNAs, suggesting that the majority of these proteomic effects result indirectly. AR and its steroid receptor coactivators (SRCs; SRC-1, -2 and -3) were recurrently affected by these SiM-miRNAs. In agreement, we identified inverse correlations between expression of these SiM-miRNAs and early clinical recurrence, as well as with AR transcriptional activity in human PC tissues. We also identified robust induction of miR-135a by androgen and strong direct binding of AR to the miR-135a locus. As miR-135a potently suppresses AR expression, this results in a negative feedback loop that suppresses AR protein expression in an androgen-dependent manner, while de-repressing AR expression upon androgen deprivation. Our results demonstrate that epigenetic silencing of these SiM-miRNAs can result in increased AR axis activity and cell proliferation, thus contributing to disease progression. We further demonstrate that a negative feedback loop involving miR-135a can restore AR expression under androgen deprivation conditions, thus contributing to the upregulation of AR protein expression in castration-resistant PC. Finally, our unbiased proteomic profiling demonstrates that the majority of actual protein expression changes induced by SiM-miRNAs cannot be explained based on predicted direct interactions. PMID- 26364609 TI - Ceramide limits phosphatidylinositol-3-kinase C2beta-controlled cell motility in ovarian cancer: potential of ceramide as a metastasis-suppressor lipid. AB - Targeting cell motility, which is required for dissemination and metastasis, has therapeutic potential for ovarian cancer metastasis, and regulatory mechanisms of cell motility need to be uncovered for developing novel therapeutics. Invasive ovarian cancer cells spontaneously formed protrusions, such as lamellipodia, which are required for generating locomotive force in cell motility. Short interfering RNA screening identified class II phosphatidylinositol 3-kinase C2beta (PI3KC2beta) as the predominant isoform of PI3K involved in lamellipodia formation of ovarian cancer cells. The bioactive sphingolipid ceramide has emerged as an antitumorigenic lipid, and treatment with short-chain C6-ceramide decreased the number of ovarian cancer cells with PI3KC2beta-driven lamellipodia. Pharmacological analysis demonstrated that long-chain ceramide regenerated from C6-ceramide through the salvage/recycling pathway, at least in part, mediated the action of C6-ceramide. Mechanistically, ceramide was revealed to interact with the PIK-catalytic domain of PI3KC2beta and affect its compartmentalization, thereby suppressing PI3KC2beta activation and its driven cell motility. Ceramide treatment also suppressed cell motility promoted by epithelial growth factor, which is a prometastatic factor. To examine the role of ceramide in ovarian cancer metastasis, ceramide liposomes were employed and confirmed to suppress cell motility in vitro. Ceramide liposomes had an inhibitory effect on peritoneal metastasis in a murine xenograft model of human ovarian cancer. Metastasis of PI3KC2beta knocked-down cells was insensitive to treatment with ceramide liposomes, suggesting specific involvement of ceramide interaction with PI3KC2beta in metastasis suppression. Our study identified ceramide as a bioactive lipid that limits PI3KC2beta-governed cell motility, and ceramide is proposed to serve as a metastasis-suppressor lipid in ovarian cancer. These findings could be translated into developing ceramide-based therapy for metastatic diseases. PMID- 26364610 TI - The HSP90 inhibitor, 17AAG, protects the intestinal stem cell niche and inhibits graft versus host disease development. AB - Graft versus host disease (GvHD), which is the primary complication of allogeneic bone marrow transplantation, can alter the intestinal barrier targeted by activated donor T-cells. Chemical inhibition of the stress protein HSP90 was demonstrated in vitro to inhibit T-cell activation and to modulate endoplasmic reticulum (ER) stress to which intestinal cells are highly susceptible. Since the HSP90 inhibitor 17-allylamino-demethoxygeldanamycin (17AAG) is developed in clinics, we explored here its ability to control intestinal acute GvHD in vivo in two mouse GvHD models (C57BL/6?BALB/c and FVB/N?Lgr5-eGFP), ex vivo in intestine organoids and in vitro in intestinal epithelial cultures. We show that 17AAG decreases GvHD-associated mortality without impairing graft versus leukemia effect. While 17AAG effect in T-cell activation is just moderate at the dose used in vivo, we observe a striking intestinal integrity protection. At the intestine level, the drug promotes the splicing of the transcription factor X-box binding protein 1 (XBP1), which is a key component of the ER stress. This effect is associated with a decrease in intestinal damage and an increase in Lgr5(+) stem cells, Paneth cells and defensins production. The importance of XBP1 splicing control is further confirmed in cultured cells and organoids of primary intestinal epithelium where XBP1 is either shRNA depleted or inhibited with toyocamycin. In conclusion, 17AAG has a protective effect on the epithelial intestinal barrier in mouse models of acute GvHD. This compound deserves to be tested in the therapeutic control of acute GvHD. PMID- 26364611 TI - RNA helicase DDX3: a novel therapeutic target in Ewing sarcoma. AB - RNA helicase DDX3 has oncogenic activity in breast and lung cancers and is required for translation of complex mRNA transcripts, including those encoding key cell-cycle regulatory proteins. We sought to determine the expression and function of DDX3 in sarcoma cells, and to investigate the antitumor activity of a novel small molecule DDX3 inhibitor, RK-33. Utilizing various sarcoma cell lines, xenografts and human tissue microarrays, we measured DDX3 expression at the mRNA and protein levels, and evaluated cytotoxicity of RK-33 in sarcoma cell lines. To study the role of DDX3 in Ewing sarcoma, we generated stable DDX3-knockdown Ewing sarcoma cell lines using DDX3-specific small hairpin RNA (shRNA), and assessed oncogenic activity. DDX3-knockdown and RK-33-treated Ewing sarcoma cells were compared with wild-type cells using an isobaric mass-tag quantitative proteomics approach to identify target proteins impacted by DDX3 inhibition. Overall, we found high expression of DDX3 in numerous human sarcoma subtypes compared with non-malignant mesenchymal cells, and knockdown of DDX3 by RNA interference inhibited oncogenic activity in Ewing sarcoma cells. Treatment with RK-33 was preferentially cytotoxic to sarcoma cells, including chemotherapy-resistant Ewing sarcoma stem cells, while sparing non-malignant cells. Sensitivity to RK-33 correlated with DDX3 protein expression. Growth of human Ewing sarcoma xenografts expressing high DDX3 was inhibited by RK-33 treatment in mice, without overt toxicity. DDX3 inhibition altered the Ewing sarcoma cellular proteome, especially proteins involved in DNA replication, mRNA translation and proteasome function. These data support further investigation of the role of DDX3 in sarcomas, advancement of RK-33 to Ewing sarcoma clinical trials and development of RNA helicase inhibition as a novel anti-neoplastic strategy. PMID- 26364612 TI - Targeting colorectal cancer via its microenvironment by inhibiting IGF-1 receptor insulin receptor substrate and STAT3 signaling. AB - The tumor microenvironment (TME) exerts critical pro-tumorigenic effects through cytokines and growth factors that support cancer cell proliferation, survival, motility and invasion. Insulin-like growth factor-1 (IGF-1) and signal transducer and activator of transcription 3 (STAT3) stimulate colorectal cancer development and progression via cell autonomous and microenvironmental effects. Using a unique inhibitor, NT157, which targets both IGF-1 receptor (IGF-1R) and STAT3, we show that these pathways regulate many TME functions associated with sporadic colonic tumorigenesis in CPC-APC mice, in which cancer development is driven by loss of the Apc tumor suppressor gene. NT157 causes a substantial reduction in tumor burden by affecting cancer cells, cancer-associated fibroblasts (CAF) and myeloid cells. Decreased cancer cell proliferation and increased apoptosis were accompanied by inhibition of CAF activation and decreased inflammation. Furthermore, NT157 inhibited expression of pro-tumorigenic cytokines, chemokines and growth factors, including IL-6, IL-11 and IL-23 as well as CCL2, CCL5, CXCL7, CXCL5, ICAM1 and TGFbeta; decreased cancer cell migratory activity and reduced their proliferation in the liver. NT157 represents a new class of anti-cancer drugs that affect both the malignant cell and its supportive microenvironment. PMID- 26364613 TI - LncRNA HOTAIR enhances ER signaling and confers tamoxifen resistance in breast cancer. AB - Tamoxifen, an estrogen receptor (ER) antagonist, is the mainstay treatment of breast cancer and the development of resistance represents a major obstacle for a cure. Although long non-coding RNAs such as HOTAIR have been implicated in breast tumorigenesis, their roles in chemotherapy resistance remain largely unknown. In this study, we report that HOTAIR (HOX antisense intergenic RNA) is upregulated in tamoxifen-resistant breast cancer tissues compared to their primary counterparts. Mechanistically, HOTAIR is a direct target of ER-mediated transcriptional repression and is thus restored upon the blockade of ER signaling, either by hormone deprivation or by tamoxifen treatment. Interestingly, this elevated HOTAIR increases ER protein level and thus enhances ER occupancy on the chromatin and potentiates its downstream gene regulation. HOTAIR overexpression is sufficient to activate the ER transcriptional program even under hormone-deprived conditions. Functionally, we found that HOTAIR overexpression increases breast cancer cell proliferation, whereas its depletion significantly impairs cell survival and abolishes tamoxifen-resistant cell growth. In conclusion, the long non-coding RNA HOTAIR is directly repressed by ER and its upregulation promotes ligand-independent ER activities and contributes to tamoxifen resistance. PMID- 26364614 TI - Extracellular vesicle-transported Semaphorin3A promotes vascular permeability in glioblastoma. AB - Glioblastoma are malignant highly vascularized brain tumours, which feature large oedema resulting from tumour-promoted vascular leakage. The pro-permeability factor Semaphorin3A (Sema3A) produced within glioblastoma has been linked to the loss of endothelial barrier integrity. Here, we report that extracellular vesicles (EVs) released by patient-derived glioblastoma cells disrupt the endothelial barrier. EVs expressed Sema3A at their surface, which accounted for in vitro elevation of brain endothelial permeability and in vivo vascular permeability, in both skin and brain vasculature. Blocking Sema3A or its receptor Neuropilin1 (NRP1) hampered EV-mediated permeability. In vivo models using ectopically and orthotopically xenografted mice revealed that Sema3A-containing EVs were efficiently detected in the blood stream. In keeping with this idea, sera from glioblastoma multiforme (GBM) patients also contain high levels of Sema3A carried in the EV fraction that enhanced vascular permeability, in a Sema3A/NRP1-dependent manner. Our results suggest that EV-delivered Sema3A orchestrates loss of barrier integrity in glioblastoma and may be of interest for prognostic purposes. PMID- 26364617 TI - The insulin degrading enzyme activates ubiquitin and promotes the formation of K48 and K63 diubiquitin. AB - We report an ATP-dependent ubiquitin conjugation with IDE which, in turn, promotes Ub-Ub linkages in tube tests. We propose a novel function for IDE as a non-canonical ubiquitin activating enzyme. PMID- 26364616 TI - Gankyrin facilitates follicle-stimulating hormone-driven ovarian cancer cell proliferation through the PI3K/AKT/HIF-1alpha/cyclin D1 pathway. AB - Gankyrin is a regulatory subunit of the 26kD proteasome complex. As a novel oncoprotein, gankyrin is expressed aberrantly in cancers from several different sites and has been shown to contribute to oncogenesis in endometrial and cervical carcinomas. Neither gankyrin's contribution to the development of epithelial ovarian cancer nor its interaction with follicle-stimulating hormone (FSH)-driven proliferation in ovarian cancer has been studied. Here we have found that gankyrin is overexpressed in ovarian cancers compared with benign ovarian cystadenomas and that gankyrin regulates FSH upregulation of cyclin D1. Importantly, gankyrin regulates PI3K/AKT signaling by downregulating PTEN. Prolonged AKT activation by FSH stimulation of the FSH receptor (FSHR) promotes gankyrin expression, which, in turn, enhances AKT activation by inhibiting PTEN. Overexpression of gankyrin decreases hypoxia inducible factor-1alpha (HIF-1alpha) protein levels, but has little effect on HIF-1alpha mRNA levels, which could be attributed to gankyrin mediating HIF-1alpha protein stability via the ubiquitin proteasome pathway. Reduction in HIF-1alpha protein stability led to attenuation of the binding with cyclin D1 promoter, resulted in abolishment of the negative regulation of cyclin D1 by HIF-1alpha, which promotes proliferation of ovarian cancer cells. Our results document that gankyrin regulates HIF-1alpha protein stability and cyclin D1 expression, ultimately mediating FSH-driven ovarian cancer cell proliferation. PMID- 26364615 TI - Emerging strategies for cancer immunoprevention. AB - The crucial role of the immune system in the formation and progression of tumors has been widely accepted. On one hand, the surveillance role of the immune system plays an important role in endogenous tumor prevention, but on the other hand, in some special circumstances such as in chronic inflammation, the immune system can actually contribute to the formation and progression of tumors. In recent years, there has been an explosion of novel targeted immunotherapies for advanced cancers. In the present manuscript, we explore known and potential various types of cancer prevention strategies and focus on nonvaccine-based cancer preventive strategies targeting the immune system at the early stages of tumorigenesis. PMID- 26364618 TI - Second trimester amniotic fluid myo-inositol concentrations in women later developing gestational diabetes mellitus or pregnancy-induced hypertension. AB - OBJECTIVE: To evaluate myo-inositol concentrations in amniotic fluid in women later developing gestational diabetes and hypertension. METHODS: A retrospective study was carried out with three groups of amniotic fluid samples (15-18 gestational weeks): 30 gestational hypertension pregnancies, 30 gestational diabetes pregnancies, and 30 normal pregnancy. RESULTS: A significant difference was observed in myo-inositol concentrations between the median gestational diabetes values (124.0 umol/L, IQR 90.0-162.5) and the control group values (79.0 umol/L, IQR 62.0-107.5), but also with gestational hypertension median values (79.0 umol/L, IQR 67.75-92.0) (p < 0.001). CONCLUSIONS: This study has shown that myo-inositol concentrations in amniotic fluid increased significantly in women later developing gestational diabetes compared to the control group. PMID- 26364620 TI - Grey Matter Volumes in Children with Conduct Problems and Varying Levels of Callous-Unemotional Traits. AB - Genetic, behavioural and functional neuroimaging studies have revealed that different vulnerabilities characterise children with conduct problems and high levels of callous-unemotional traits (CP/HCU) compared with children with conduct problems and low callous-unemotional traits (CP/LCU). We used voxel-based morphometry to study grey matter volume (GMV) in 89 male participants (aged 10 16), 60 of whom exhibited CP. The CP group was subdivided into CP/HCU (n = 29) and CP/LCU (n = 31). Whole-brain and regional GMV were compared across groups (CP vs. typically developing (TD) controls (n = 29); and CP/HCU vs. CP/LCU vs. TD). Whole-brain analyses showed reduced GMV in left middle frontal gyrus in the CP/HCU group compared with TD controls. Region-of-interest analyses showed reduced volume in bilateral orbitofrontal cortex (OFC) in the CP group as a whole compared with TD controls. Reduced volume in left OFC was found to be driven by the CP/HCU group only, with significant reductions relative to both TD controls and the CP/LCU group, and no difference between these latter two groups. Within the CP group left OFC volume was significantly predicted by CU traits, but not conduct disorder symptoms. Reduced right anterior cingulate cortex volume was also found in CP/HCU compared with TD controls. Our results support previous findings indicating that GMV differences in brain regions central to decision making and empathy are implicated in CP. However, they extend these data to suggest that some of these differences might specifically characterise the subgroup with CP/HCU, with GMV reduction in left OFC differentiating children with CP/HCU from those with CP/LCU. PMID- 26364619 TI - Extensive identification and analysis of conserved small ORFs in animals. AB - BACKGROUND: There is increasing evidence that transcripts or transcript regions annotated as non-coding can harbor functional short open reading frames (sORFs). Loss-of-function experiments have identified essential developmental or physiological roles for a few of the encoded peptides (micropeptides), but genome wide experimental or computational identification of functional sORFs remains challenging. RESULTS: Here, we expand our previously developed method and present results of an integrated computational pipeline for the identification of conserved sORFs in human, mouse, zebrafish, fruit fly, and the nematode C. elegans. Isolating specific conservation signatures indicative of purifying selection on amino acid (rather than nucleotide) sequence, we identify about 2,000 novel small ORFs located in the untranslated regions of canonical mRNAs or on transcripts annotated as non-coding. Predicted sORFs show stronger conservation signatures than those identified in previous studies and are sometimes conserved over large evolutionary distances. The encoded peptides have little homology to known proteins and are enriched in disordered regions and short linear interaction motifs. Published ribosome profiling data indicate translation of more than 100 novel sORFs, and mass spectrometry data provide evidence for more than 70 novel candidates. CONCLUSIONS: Taken together, we identify hundreds of previously unknown conserved sORFs in major model organisms. Our computational analyses and integration with experimental data show that these sORFs are expressed, often translated, and sometimes widely conserved, in some cases even between vertebrates and invertebrates. We thus provide an integrated resource of putatively functional micropeptides for functional validation in vivo. PMID- 26364622 TI - Child Maltreatment Among Singletons and Multiple Births in Japan: A Population Based Study. AB - BACKGROUND: The occurrence of multiple births has been recognized as a risk factor for child maltreatment. However, few population-based studies have examined the relationship between multiple births and child maltreatment. This study aimed to evaluate the degree of risk of child maltreatment among singletons and multiple births in Japan and to identify factors associated with increased risk. METHODS: Using population-based data, we analyzed the database of records on child maltreatment and medical checkups for infants aged 1.5 years filed at Nishinomiya City Public Health Center between April 2007 and March 2011. To protect personal information, the data were transferred to anonymized electronic files for analysis. RESULTS: After adjusting by logistic regression for each associated factor and gestation number, multiples themselves were not associated with the risk of child maltreatment. However, compared with singletons, multiples had a significantly higher rate of risk factors for child maltreatment, including low birth weight and neural abnormality. Moreover, compared with mothers of singleton, mothers of twins had a significantly higher rate of poor health, which is a risk factor of child maltreatment. CONCLUSION: Multiples were not associated with the risk of child maltreatment. However, compared with singletons, multiples and their mothers had a significantly higher rate of risk factors of child maltreatment. PMID- 26364621 TI - Marijuana use and risk of prediabetes and diabetes by middle adulthood: the Coronary Artery Risk Development in Young Adults (CARDIA) study. AB - AIMS/HYPOTHESIS: The impact of marijuana use on metabolic health is largely unknown. This study sought to clarify the cross-sectional and longitudinal associations between self-reported marijuana use, and prediabetes (defined as fasting glucose 5.6-6.9 mmol/l, 2 h glucose post OGTT 7.8-11.0 mmol/l or HbA1c 5.7-6.4% [39-47 mmol/mol]) and diabetes. METHODS: Data from the community-based Coronary Artery Risk Development in Young Adults (CARDIA) study were used to determine marijuana use and the presence of prediabetes and diabetes among participants. The association between marijuana use and the prevalence of prediabetes and diabetes was examined in 3,034 participants at CARDIA examination year 25 (2010-2011), while the incidence of prediabetes and diabetes according to previous marijuana use was assessed in 3,151 individuals who were free from prediabetes/diabetes at year 7 (1992-1993) and who returned for at least one of the four subsequent follow-up examinations over 18 years. RESULTS: The percentage of individuals who self-reported current use of marijuana declined over the course of the study's follow-up. After multivariable adjustment, higher odds of prediabetes were found for individuals who reported current use of marijuana (OR 1.65 [95% CI 1.15, 2.38]) and a lifetime use of 100 times or more (OR 1.49 [95% CI 1.06, 2.11]), compared with individuals who reported never using marijuana. There was no association between marijuana use and diabetes at CARDIA examination year 25. Over 18 years of follow-up, a greater risk of prediabetes (but not diabetes) was found for individuals who reported a lifetime use of marijuana of 100 times or more (HR 1.39 [95% CI 1.13, 1.71]), compared with individuals who had never used marijuana. CONCLUSIONS/INTERPRETATION: Marijuana use in young adulthood is associated with an increased risk of prediabetes by middle adulthood, but not with the development of diabetes by this age. PMID- 26364623 TI - Effects of flavonol-rich green tea cultivar (Camellia sinensis L.) on plasma oxidized LDL levels in hypercholesterolemic mice. AB - To examine the possible benefits of tea flavonols, we compared anti-atherogenic effects between common and flavonol-rich tea cultivars. The tea infusion made from a flavonol-rich cultivar, but not a common cultivar, significantly decreased the plasma oxidized low-density lipoprotein level in mice fed a high-cholesterol diet. The result suggests that tea flavonols have the potential to protect against cardiovascular diseases. PMID- 26364624 TI - Using patient-specific induced pluripotent stem cells to interrogate the pathogenicity of a novel retinal pigment epithelium-specific 65 kDa cryptic splice site mutation and confirm eligibility for enrollment into a clinical gene augmentation trial. AB - Retinal pigment epithelium-specific 65 kDa (RPE65)-associated Leber congenital amaurosis is an autosomal recessive disease that results in reduced visual acuity and night blindness beginning at birth. It is one of the few retinal degenerative disorders for which promising clinical gene transfer trials are currently underway. However, the ability to enroll patients in a gene augmentation trial is dependent on the identification of 2 bona fide disease-causing mutations, and there are some patients with the phenotype of RPE65-associated disease who might benefit from gene transfer but are ineligible because 2 disease-causing genetic variations have not yet been identified. Some such patients have novel mutations in RPE65 for which pathogenicity is difficult to confirm. The goal of this study was to determine if an intronic mutation identified in a 2-year-old patient with presumed RPE65-associated disease was truly pathogenic and grounds for inclusion in a clinical gene augmentation trial. Sequencing of the RPE65 gene revealed 2 mutations: (1) a previously identified disease-causing exonic leucine-to-proline mutation (L408P) and (2) a novel single point mutation in intron 3 (IVS3-11) resulting in an A>G change. RT-PCR analysis using RNA extracted from control human donor eye-derived primary RPE, control iPSC-RPE cells, and proband iPSC-RPE cells revealed that the identified IVS3-11 variation caused a splicing defect that resulted in a frameshift and insertion of a premature stop codon. In this study, we demonstrate how patient-specific iPSCs can be used to confirm pathogenicity of unknown mutations, which can enable positive clinical outcomes. PMID- 26364625 TI - Multiple neurofibromas occupying all the neural foramens. PMID- 26364626 TI - Exploring the Oxidation of Lignin-Derived Phenols by a Library of Laccase Mutants. AB - Saturation mutagenesis was performed over six residues delimiting the substrate binding pocket of a fungal laccase previously engineered in the lab. Mutant libraries were screened using sinapic acid as a model substrate, and those mutants presenting increased activity were selected for exploring the oxidation of lignin-derived phenols. The latter comprised a battery of phenolic compounds of interest due to their use as redox mediators or precursors of added-value products and their biological activity. The new laccase variants were investigated in a multi-screening assay and the structural determinants, at both the substrate and the protein level, for the oxidation of the different phenols are discussed. Laccase activity greatly varied only by changing one or two residues of the enzyme pocket. Our results suggest that once the redox potential threshold is surpassed, the contribution of the residues of the enzymatic pocket for substrate recognition and binding strongly influence the overall rate of the catalytic reaction. PMID- 26364627 TI - Synthetic Routes to N-9 Alkylated 8-Oxoguanines; Weak Inhibitors of the Human DNA Glycosylase OGG1. AB - The human 8-oxoguanine DNA glycosylase OGG1 is involved in base excision repair (BER), one of several DNA repair mechanisms that may counteract the effects of chemo- and radiation therapy for the treatment of cancer. We envisage that potent inhibitors of OGG1 may be found among the 9-alkyl-8-oxoguanines. Thus we explored synthetic routes to 8-oxoguanines and examined these as OGG1 inhibitors. The best reaction sequence started from 6-chloroguanine and involved N-9 alkylation, C-8 bromination, and finally simultaneous hydrolysis of both halides. Bromination before N-alkylation should only be considered when the N-substituent is not compatible with bromination conditions. The 8-oxoguanines were found to be weak inhibitors of OGG1. 6-Chloro-8-oxopurines, byproducts in the hydrolysis of 2,6 halopurines, turned out to be slightly better inhibitors than the corresponding 8 oxoguanines. PMID- 26364628 TI - Concise Synthesis of Broussonone A. AB - A concise and expeditious approach to the total synthesis of broussonone A, a p quinol natural compound, has been developed. The key features of the synthesis include the Grubbs II catalyst mediated cross metathesis of two aromatic subunits, and a chemoselective oxidative dearomatizationin the presence of two phenol moieties. Especially, optimization associated with the CM reaction of ortho-alkoxystyrenes was also studied, which are known to be ineffective for Ru catalyzed metathesis reactions under conventional reaction conditions because ortho-alkoxy group could coordinate to the ruthenium center, resulting in the potential complication of catalyst inhibition. PMID- 26364629 TI - Synthesis and Preliminary Biological Evaluation of 1,3,5-Triazine Amino Acid Derivatives to Study Their MAO Inhibitors. AB - Three series of 4,6-dimethoxy-, 4,6-dipiperidino- and 4,6-dimorpholino-1,3,5 triazin-2-yl) amino acid derivatives were synthesized and characterized. A preliminary study for their monoamine oxidase inhibitory activity showed that compounds 7, 18, and 25 had MAO-A inhibition activity comparable to that of the standard clorgyline, with apparently more selective inhibitory activity toward MAO-A than MAO-B and no significant acute toxicity. PMID- 26364630 TI - Antioxidant and Anti-Inflammatory Activities of a Natural Compound, Shizukahenriol, through Nrf2 Activation. AB - Imbalance in the antioxidant defense system leads to detrimental consequences, such as neurological disorders. The Nrf2 signaling is known as a main pathway involved in cellular defense system. Nrf2 is a transcription factor that regulates oxidative stress response by inducing expression of various antioxidant enzyme genes. In this study, we screened several pure natural compounds for Nrf2 activator. Among them, shizukahenriol (SZH), isolated from Chloranthus henryi, activated Nrf2, and induced expression of the Nrf2-dependent antioxidant enzymes HO-1, GCLC, and GCLM in BV-2 microglial cells. This natural compound was also effective in suppressing production of inflammatory molecules NO, TNF-alpha, and inhibition of NF-kappaB p65 translocation to the nucleus in a dose-dependent manner. We also examined whether SZH rescued the microglial cells from oxidative stress-induced cell death. Pretreatment with SZH dose-dependently attenuated H2O2 induced cytotoxicity in BV-2 microglial cells. These results suggested SZH as a potential neuroprotective agent for neurological disorders. PMID- 26364631 TI - Adsorption and Corrosion Inhibition Studies of Some Selected Dyes as Corrosion Inhibitors for Mild Steel in Acidic Medium: Gravimetric, Electrochemical, Quantum Chemical Studies and Synergistic Effect with Iodide Ions. AB - The corrosion inhibition properties of some organic dyes, namely Sunset Yellow (SS), Amaranth (AM), Allura Red (AR), Tartrazine (TZ) and Fast Green (FG), for mild steel corrosion in 0.5 M HCl solution, were investigated using gravimetric, potentiodynamic polarization techniques and quantum chemical calculations. The results showed that the studied dyes are good corrosion inhibitors with enhanced inhibition efficiencies. The inhibition efficiency of all the studied dyes increases with increase in concentration, and decreases with increase in temperature. The results showed that the inhibition efficiency of the dyes increases in the presence of KI due to synergistic interactions of the dye molecules with iodide (I(-)) ions. Potentiodynamic polarization results revealed that the studied dyes are mixed-type inhibitors both in the absence and presence of KI. The adsorption of the studied dyes on mild steel surface, with and without KI, obeys the Langmuir adsorption isotherm and involves physical adsorption mechanism. Quantum chemical calculations revealed that the most likely sites in the dye molecules for interactions with mild steel are the S, O, and N heteroatoms. PMID- 26364632 TI - RNA Aptamers as Molecular Tools to Study the Functionality of the Hepatitis C Virus CRE Region. AB - BACKGROUND: Hepatitis C virus (HCV) contains a (+) ssRNA genome with highly conserved structural, functional RNA domains, many of them with unknown roles for the consecution of the viral cycle. Such genomic domains are candidate therapeutic targets. This study reports the functional characterization of a set of aptamers targeting the cis-acting replication element (CRE) of the HCV genome, an essential partner for viral replication and also involved in the regulation of protein synthesis. METHODS: Forty-four aptamers were tested for their ability to interfere with viral RNA synthesis in a subgenomic replicon system. Some of the most efficient inhibitors were further evaluated for their potential to affect the recruitment of the HCV RNA-dependent RNA polymerase (NS5B) and the viral translation in cell culture. RESULTS: Four aptamers emerged as potent inhibitors of HCV replication by direct interaction with functional RNA domains of the CRE, yielding a decrease in the HCV RNA levels higher than 90%. Concomitantly, one of them also induced a significant increase in viral translation (>50%). The three remaining aptamers efficiently competed with the binding of the NS5B protein to the CRE. CONCLUSIONS: Present findings confirm the potential of the CRE as an anti-HCV target and support the use of aptamers as molecular tools for investigating the functionality of RNA domains in viral genomes. PMID- 26364633 TI - Synthesis of Novel 2,5-Disubstituted-1,3,4-thiadiazoles Clubbed 1,2,4-Triazole, 1,3,4-Thiadiazole, 1,3,4-Oxadiazole and/or Schiff Base as Potential Antimicrobial and Antiproliferative Agents. AB - In the present study, a new series of 2,5-disubstituted-1,3,4-thiadiazole tethered 1,2,4-triazole, 1,3,4-thiadiazole, 1,3,4-oxadiazole and Schiff base derivatives were synthesized and characterized by IR, 1H-NMR, (13)C-NMR, MS and elemental analyses. All compounds were screened for their antibacterial, antifungal and antiproliferative activity. Some of the synthesized derivatives have displayed promising biological activity. PMID- 26364634 TI - Comparing the Antibacterial and Functional Properties of Cameroonian and Manuka Honeys for Potential Wound Healing-Have We Come Full Cycle in Dealing with Antibiotic Resistance? AB - The increased incidence of bacterial resistance to antibiotics has generated renewed interest in "traditional" antimicrobials, such as honey. This paper reports on a study comparing physico-chemical, antioxidant and antibacterial characteristics (that potentially contribute in part, to the functional wound healing activity) of Cameroonian honeys with those of Manuka honey. Agar well diffusion was used to generate zones of inhibition against Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus while broth dilutions were used to study the minimum inhibitory concentrations (MICs). Non-peroxide activity was investigated by catalase for hydrogen peroxide reduction. The Cameroonian honeys demonstrated functional properties similar to Manuka honey, with strong correlations between the antioxidant activity and total phenol content of each honey. They were also as effective as Manuka honey in reducing bacteria load with an MIC of 10% w/v against all three bacteria and exhibited non-peroxide antimicrobial activity. These Cameroon honeys have potential therapeutic activity and may contain compounds with activity against Gram positive and Gram negative bacteria. Antibacterial agents from such natural sources present a potential affordable treatment of wound infections caused by antibiotic resistant bacteria, which are a leading cause of amputations and deaths in many African countries. PMID- 26364635 TI - Universal Capacitance Model for Real-Time Biomass in Cell Culture. AB - : Capacitance probes have the potential to revolutionize bioprocess control due to their safe and robust use and ability to detect even the smallest capacitors in the form of biological cells. Several techniques have evolved to model biomass statistically, however, there are problems with model transfer between cell lines and process conditions. Errors of transferred models in the declining phase of the culture range for linear models around +100% or worse, causing unnecessary delays with test runs during bioprocess development. The goal of this work was to develop one single universal model which can be adapted by considering a potentially mechanistic factor to estimate biomass in yet untested clones and scales. The novelty of this work is a methodology to select sensitive frequencies to build a statistical model which can be shared among fermentations with an error between 9% and 38% (mean error around 20%) for the whole process, including the declining phase. A simple linear factor was found to be responsible for the transferability of biomass models between cell lines, indicating a link to their phenotype or physiology. PMID- 26364636 TI - Smartphone-Based Bioelectrical Impedance Analysis Devices for Daily Obesity Management. AB - Current bioelectric impedance analysis (BIA) systems are often large, cumbersome devices which require strict electrode placement on the user, thus inhibiting mobile capabilities. In this work, we developed a handheld BIA device that measures impedance from multiple frequencies (5 kHz~200 kHz) with four contact electrodes and evaluated the BIA device against standard body composition analysis systems: a dual-energy X-ray absorptiometry (DXA) system (GE Lunar Prodigy, GE Healthcare, Buckinghamshire, UK) and a whole-body BIA system (InBody S10, InBody, Co. Ltd, Seoul, Korea). In the study, 568 healthy participants, varying widely in body mass index, age, and gender, were recruited at two research centers: the Samsung Medical Center (SMC) in South Korea and the Pennington Biomedical Research Center (PBRC) in the United States. From the measured impedance data, we analyzed individual body fat and skeletal muscle mass by applying linear regression analysis against target reference data. Results indicated strong correlations of impedance measurements between the prototype pathways and corresponding InBody S10 electrical pathways (R = 0.93, p < 0.0001). Additionally, body fat estimates from DXA did not yield significant differences (p > 0.728 (paired t-test), DXA mean body fat 29.45 +/- 10.77 kg, estimated body fat 29.52 +/- 12.53 kg). Thus, this portable BIA system shows a promising ability to estimate an individual's body composition that is comparable to large stationary BIA systems. PMID- 26364637 TI - A New Reassigned Spectrogram Method in Interference Detection for GNSS Receivers. AB - Interference detection is very important for Global Navigation Satellite System (GNSS) receivers. Current work on interference detection in GNSS receivers has mainly focused on time-frequency (TF) analysis techniques, such as spectrogram and Wigner-Ville distribution (WVD), where the spectrogram approach presents the TF resolution trade-off problem, since the analysis window is used, and the WVD method suffers from the very serious cross-term problem, due to its quadratic TF distribution nature. In order to solve the cross-term problem and to preserve good TF resolution in the TF plane at the same time, in this paper, a new TF distribution by using a reassigned spectrogram has been proposed in interference detection for GNSS receivers. This proposed reassigned spectrogram method efficiently combines the elimination of the cross-term provided by the spectrogram itself according to its inherent nature and the improvement of the TF aggregation property achieved by the reassignment method. Moreover, a notch filter has been adopted in interference mitigation for GNSS receivers, where receiver operating characteristics (ROCs) are used as metrics for the characterization of interference mitigation performance. The proposed interference detection method by using a reassigned spectrogram is evaluated by experiments on GPS L1 signals in the disturbing scenarios in comparison to the state-of-the-art TF analysis approaches. The analysis results show that the proposed interference detection technique effectively overcomes the cross-term problem and also keeps good TF localization properties, which has been proven to be valid and effective to enhance the interference Sensors 2015, 15 22168 detection performance; in addition, the adoption of the notch filter in interference mitigation has shown a significant acquisition performance improvement in terms of ROC curves for GNSS receivers in jamming environments. PMID- 26364638 TI - Simulations of Interdigitated Electrode Interactions with Gold Nanoparticles for Impedance-Based Biosensing Applications. AB - In this paper, we describe a point-of-care biosensor design. The uniqueness of our design is in its capability for detecting a wide variety of target biomolecules and the simplicity of nanoparticle enhanced electrical detection. The electrical properties of interdigitated electrodes (IDEs) and the mechanism for gold nanoparticle-enhanced impedance-based biosensor systems based on these electrodes are simulated using COMSOL Multiphysics software. Understanding these properties and how they can be affected is vital in designing effective biosensor devices. Simulations were used to show electrical screening develop over time for IDEs in a salt solution, as well as the electric field between individual digits of electrodes. Using these simulations, it was observed that gold nanoparticles bound closely to IDEs can lower the electric field magnitude between the digits of the electrode. The simulations are also shown to be a useful design tool in optimizing sensor function. Various different conditions, such as electrode dimensions and background ion concentrations, are shown to have a significant impact on the simulations. PMID- 26364639 TI - Real-Time QoS Routing Protocols in Wireless Multimedia Sensor Networks: Study and Analysis. AB - Many routing protocols have been proposed for wireless sensor networks. These routing protocols are almost always based on energy efficiency. However, recent advances in complementary metal-oxide semiconductor (CMOS) cameras and small microphones have led to the development of Wireless Multimedia Sensor Networks (WMSN) as a class of wireless sensor networks which pose additional challenges. The transmission of imaging and video data needs routing protocols with both energy efficiency and Quality of Service (QoS) characteristics in order to guarantee the efficient use of the sensor nodes and effective access to the collected data. Also, with integration of real time applications in Wireless Senor Networks (WSNs), the use of QoS routing protocols is not only becoming a significant topic, but is also gaining the attention of researchers. In designing an efficient QoS routing protocol, the reliability and guarantee of end-to-end delay are critical events while conserving energy. Thus, considerable research has been focused on designing energy efficient and robust QoS routing protocols. In this paper, we present a state of the art research work based on real-time QoS routing protocols for WMSNs that have already been proposed. This paper categorizes the real-time QoS routing protocols into probabilistic and deterministic protocols. In addition, both categories are classified into soft and hard real time protocols by highlighting the QoS issues including the limitations and features of each protocol. Furthermore, we have compared the performance of mobility-aware query based real-time QoS routing protocols from each category using Network Simulator-2 (NS2). This paper also focuses on the design challenges and future research directions as well as highlights the characteristics of each QoS routing protocol. PMID- 26364640 TI - Multi-Wavelength Based Optical Density Sensor for Autonomous Monitoring of Microalgae. AB - A multi-wavelength based optical density sensor unit was designed, developed, and evaluated to monitor microalgae growth in real time. The system consisted of five main components including: (1) laser diode modules as light sources; (2) photodiodes as detectors; (3) driver circuit; (4) flow cell; and (5) sensor housing temperature controller. The sensor unit was designed to be integrated into any microalgae culture system for both real time and non-real time optical density measurements and algae growth monitoring applications. It was shown that the sensor unit was capable of monitoring the dynamics and physiological changes of the microalgae culture in real-time. Algae biomass concentration was accurately estimated with optical density measurements at 650, 685 and 780 nm wavelengths used by the sensor unit. The sensor unit was able to monitor cell concentration as high as 1.05 g.L(-1) (1.51 * 108 cells.mL(-1)) during the culture growth without any sample preparation for the measurements. Since high cell concentrations do not need to be diluted using the sensor unit, the system has the potential to be used in industrial microalgae cultivation systems for real time monitoring and control applications that can lead to improved resource use efficiency. PMID- 26364641 TI - Mercury Toxicity and Contamination of Households from the Use of Skin Creams Adulterated with Mercurous Chloride (Calomel). AB - Inorganic mercury, in the form of mercurous chloride, or calomel, is intentionally added to some cosmetic products sold through informal channels in Mexico and the US for skin lightening and acne treatment. These products have led to multiple cases of mercury poisoning but few investigations have addressed the contamination of cream users' homes. We report on several cases of mercury poisoning among three Mexican-American families in California from use of mercury containing skin creams. Each case resulted in widespread household contamination and secondary contamination of family members. Urine mercury levels in cream users ranged from 37 to 482 ug/g creatinine and in non-users from non-detectable to 107 ug/g creatinine. Air concentrations of up to 8 ug/m3 of mercury within homes exceeded the USEPA/ATSDR health-based guidance and action level of <1.0 MUg/m3. Mercury contamination of cream users' homes presented a multi-pathway exposure environment to residents. Homes required extensive decontamination, including disposal of most household items, to achieve acceptable air levels. The acceptable air levels used were not designed to consider multi-pathway exposure scenarios. These findings support that the calomel is able to change valence form to elemental mercury and volatilize once exposed to the skin or surfaces in the indoor environment. PMID- 26364642 TI - Evaluation of the AnnAGNPS Model for Predicting Runoff and Nutrient Export in a Typical Small Watershed in the Hilly Region of Taihu Lake. AB - The application of hydrological and water quality models is an efficient approach to better understand the processes of environmental deterioration. This study evaluated the ability of the Annualized Agricultural Non-Point Source (AnnAGNPS) model to predict runoff, total nitrogen (TN) and total phosphorus (TP) loading in a typical small watershed of a hilly region near Taihu Lake, China. Runoff was calibrated and validated at both an annual and monthly scale, and parameter sensitivity analysis was performed for TN and TP before the two water quality components were calibrated. The results showed that the model satisfactorily simulated runoff at annual and monthly scales, both during calibration and validation processes. Additionally, results of parameter sensitivity analysis showed that the parameters Fertilizer rate, Fertilizer organic, Canopy cover and Fertilizer inorganic were more sensitive to TN output. In terms of TP, the parameters Residue mass ratio, Fertilizer rate, Fertilizer inorganic and Canopy cover were the most sensitive. Based on these sensitive parameters, calibration was performed. TN loading produced satisfactory results for both the calibration and validation processes, whereas the performance of TP loading was slightly poor. The simulation results showed that AnnAGNPS has the potential to be used as a valuable tool for the planning and management of watersheds. PMID- 26364643 TI - Taxonomic Characterization and Secondary Metabolite Profiling of Aspergillus Section Aspergillus Contaminating Feeds and Feedstuffs. AB - Xerophilic fungal species of the genus Aspergillus are economically highly relevant due to their ability to grow on low water activity substrates causing spoilage of stored goods and animal feeds. These fungi can synthesize a variety of secondary metabolites, many of which show animal toxicity, creating a health risk for food production animals and to humans as final consumers, respectively. Animal feeds used for rabbit, chinchilla and rainbow trout production in Argentina were analysed for the presence of xerophilic Aspergillus section Aspergillus species. High isolation frequencies (>60%) were detected in all the studied rabbit and chinchilla feeds, while the rainbow trout feeds showed lower fungal charge (25%). These section Aspergillus contaminations comprised predominantly five taxa. Twenty isolates were subjected to taxonomic characterization using both ascospore SEM micromorphology and two independent DNA loci sequencing. The secondary metabolite profiles of the isolates were determined qualitatively by HPLC-MS. All the isolates produced neoechinulin A, 17 isolates were positive for cladosporin and echinulin, and 18 were positive for neoechinulin B. Physcion and preechinulin were detected in a minor proportion of the isolates. This is the first report describing the detailed species composition and the secondary metabolite profiles of Aspergillus section Aspergillus contaminating animal feeds. PMID- 26364645 TI - Does Employee Recognition Affect Positive Psychological Functioning and Well Being? AB - Employee recognition is one of the typical characteristics of healthy organizations. The majority of research on recognition has studied the consequences of this variable on workers. But few investigations have focused on understanding what mechanisms mediate between recognition and its consequences. This work aims to understand whether the relationship between employee recognition and well-being, psychological resources mediate. To answer this question a sample of 1831 workers was used. The variables measured were: employee recognition, subjective well-being and positive psychological functioning (PPF), which consists of 11 psychological resources. In the analysis of data, structural equation models were applied. The results confirmed our hypothesis and showed that PPF mediate the relationship between recognition and well-being. The effect of recognition over PPF is two times greater (.39) with peer-recognition than with supervisor-recognition (.20), and, the effect of PPF over well-being is .59. This study highlights the importance of promoting employee recognition policies in organizations for the impact it has, not only on well-being, but also on the positive psychological functioning of the workers. PMID- 26364644 TI - In silico modeling of spore inhalation reveals fungal persistence following low dose exposure. AB - The human lung is constantly exposed to spores of the environmental mould Aspergillus fumigatus, a major opportunistic pathogen. The spectrum of resultant disease is the outcome of complex host-pathogen interactions, an integrated, quantitative understanding of which lies beyond the ethical and technical reach permitted by animal studies. Here we construct a mathematical model of spore inhalation and clearance by concerted actions of macrophages and neutrophils, and use it to derive a mechanistic understanding of pathogen clearance by the healthy, immunocompetent host. In particular, we investigated the impact of inoculum size upon outcomes of single-dose fungal exposure by simulated titrations of inoculation dose, from 10(6) to 10(2) spores. Simulated low-dose (10(2)) spore exposure, an everyday occurrence for humans, revealed a counter intuitive prediction of fungal persistence (>3 days). The model predictions were reflected in the short-term dynamics of experimental murine exposure to fungal spores, thereby highlighting the potential of mathematical modelling for studying relevant behaviours in experimental models of fungal disease. Our model suggests that infectious outcomes can be highly dependent upon short-term dynamics of fungal exposure, which may govern occurrence of cyclic or persistent subclinical fungal colonisation of the lung following low dose spore inhalation in non neutropenic hosts. PMID- 26364646 TI - High burden of invasive group A streptococcal disease in the Northern Territory of Australia. AB - Although the incidence of invasive group A streptococcal disease in northern Australia is very high, little is known of the regional epidemiology and molecular characteristics. We conducted a case series of Northern Territory residents reported between 2011 and 2013 with Streptococcus pyogenes isolates from a normally sterile site. Of the 128 reported episodes, the incidence was disproportionately high in the Indigenous population at 69.7/100 000 compared to 8.8/100 000 in the non-Indigenous population. Novel to the Northern Territory is the extremely high incidence in haemodialysis patients of 2205.9/100 000 population; and for whom targeted infection control measures could prevent transmission. The incidences in the tropical north and semi-arid Central Australian regions were similar. Case fatality was 8% (10/128) and streptococcal toxic shock syndrome occurred in 14 (11%) episodes. Molecular typing of 82 isolates identified 28 emm types, of which 63 (77%) were represented by four emm clusters. Typing confirmed transmission between infant twins. While the diverse range of emm types presents a challenge for effective coverage by vaccine formulations, the limited number of emm clusters raises optimism should cluster specific cross-protection prove efficacious. Further studies are required to determine effectiveness of chemoprophylaxis for contacts and to inform public health response. PMID- 26364647 TI - Bandgap Engineering of Phosphorene by Laser Oxidation toward Functional 2D Materials. AB - We demonstrate a straightforward and effective laser pruning approach to reduce multilayer black phosphorus (BP) to few-layer BP under ambient condition. Phosphorene oxides and suboxides are formed and the degree of laser-induced oxidation is controlled by the laser power. Since the band gaps of the phosphorene suboxide depend on the oxygen concentration, this simple technique is able to realize localized band gap engineering of the thin BP. Micropatterns of few-layer phosphorene suboxide flakes with unique optical and fluorescence properties are created. Remarkably, some of these suboxide flakes display long term (up to 2 weeks) stability in ambient condition. Comparing against the optical properties predicted by first-principle calculations, we develop a "calibration" map in using focused laser power as a handle to tune the band gap of the BP suboxide flake. Moreover, the surface of the laser patterned region is altered to be sensitive to toxic gas by way of fluorescence contrast. Therefore, the multicolored display is further demonstrated as a toxic gas monitor. In addition, the BP suboxide flake is demonstrated to exhibit higher drain current modulation and mobility comparable to that of the pristine BP in the electronic application. PMID- 26364648 TI - Pharmacogenetics of clozapine treatment response and side-effects in schizophrenia: an update. AB - INTRODUCTION: Clozapine (CLZ) is the most effective treatment for treatment resistant schizophrenia (SCZ) patients, with potential added benefits of reduction in suicide risk and aggression. However, CLZ is also mainly underused due to its high risk for the potentially lethal side-effect of agranulocytosis as well as weight gain and related metabolic dysregulation. Pharmacogenetics promises to enable the prediction of patient treatment response and risk of adverse effects based on patients' genetics, paving the way toward individualized treatment. AREA COVERED: This article reviews pharmacogenetics studies of CLZ response and side-effects with a focus on articles from January 2012 to February 2015, as an update to the previous reviews. Pharmacokinetic genes explored primarily include CYP1A2, while pharmacodynamic genes consisted of traditional pharmacogenetic targets such as brain-derived neurotrophic factor as well novel mitochondrial genes, NDUFS-1 and translocator protein. EXPERT OPINION: Pharmacogenetics is a promising avenue for individualized medication of CLZ in SCZ, with several consistently replicated gene variants predicting CLZ response and side-effects. However, a large proportion of studies have yielded mixed results. Large-scale Genome-wide association studies (e.g., CRESTAR) and targeted gene studies with standardized designs (response measurements, treatment durations, plasma level monitoring) are required for further progress toward clinical translation. Additionally, in order to improve study quality, we recommend accounting for important confounders, including polypharmacy, baseline measurements, treatment duration, gender, and age at onset. PMID- 26364649 TI - Comparative effects of cocaine and cocaethylene on alveolar epithelial type II cells. AB - Abuse of cocaine (COC) and alcohol have been among the leading causes of non prescription drug-related deaths in the USA and are known to cause acute and chronic lung diseases. The co-abuse of COC and alcohol results in the production of an active metabolite, cocaethylene (CE). The effects of COC and its metabolites on the respiratory system have been scarcely studied. This study was aimed at comparing the toxic effects of eqimolar concentration (1 mM) of COC and CE on alveolar epithelial type II cells. This was performed by measuring cell growth, viability, clonogenic activity, cell cycle and reactive oxygen species (ROS) generation. The treatment of CE and COC resulted in a significant inhibition of cell proliferation with the formation of an average of three colonies which measured about 1.74*10(-15) m each and 25 colonies each of about 5.73*10(-15) m, respectively, while untreated cells yielded 31 colonies of 8.75*10(-15) m (p<0.05). The treatments of CE and COC resulted in the reduction of the growth fraction of alveolar epithelial type II cells without significant decrease in viability. In addition, there was an approximately twofold increase in ROS generation as compared to the controls (p<0.05). Therefore, CE-induced inhibition of cellular proliferation may contribute to the pathogenesis of diffuse alveolar damage in co-abusers of COC and alcohol. PMID- 26364650 TI - Home blood pressure measurements: advantages and disadvantages compared to office and ambulatory monitoring. AB - Home blood pressure monitoring (HBPM) is an easy and standardized tool to measure blood pressure (BP) at home, which is recommended by several national and international guidelines to obtain reliable BP values. It is a useful and dependable measure of BP, which can add information to the more common and standardized methods, such as office (OBPM) and ambulatory blood pressure measurement (ABPM), and sometimes substitute for them. Along with ABPM, HBPM detects out-of-office BP levels, helping to identify the white-coat effect and masked hypertension. Moreover, the large number of BP measurements obtained with HBPM has been demonstrated to be associated with future cardiovascular events and to provide information on day-to-day variability; this is a new aspect, the clinical significance of which is still under evaluation. By giving patients a more active role in the management of their chronic disease, HBPM can improve treatment adherence. The present review focuses on all these aspects and describes the pros and cons of HBPM use compared to OBPM and ABPM. In conclusion, although some aspects need to be clarified, the scientific evidence collected so far should encourage the more widespread use of HBPM in clinical practice. PMID- 26364651 TI - Maternal perception of fetal movements in late pregnancy is affected by type and duration of fetal movement. AB - OBJECTIVE: A reduction in fetal movements has been proposed to identify pregnancies at risk of stillbirth. The utility of this approach is limited by variability in maternal perception of fetal movements. We aimed to determine the proportion of fetal movements observed by ultrasound that were maternally perceived and identify factors that affected maternal perception. METHOD: During 30-min recordings, women (n = 21) depressed a trigger upon perception of a fetal movement, while an ultrasound operator recorded observed movements according to the fetal parts involved. RESULTS: Women perceived between 2.4% and 81.0% (median 44.8%) of movements observed on scan. Synchronous movement of the fetal trunk and limbs was more likely to be recognized than either part in isolation (60.5% versus 37.5% and 30%, respectively). The ultrasound operator judged the fetus to be moving for a significantly greater proportion of the time than mothers (median 1.5% of total recording time versus 0.7%). There was no significant relationship between the ability to perceive fetal activity and placental site, parity, amniotic fluid index or maternal body mass index. CONCLUSION: Variations in maternal perception of fetal movements may affect detection of a clinically significant reduction in fetal movements for some women. PMID- 26364653 TI - Themenubersicht. PMID- 26364652 TI - Vorwort. PMID- 26364655 TI - Autorenverzeichnis. PMID- 26364656 TI - Inhaltsverzeichnis. PMID- 26364657 TI - Insight into the binding mode of a novel LSD1 inhibitor by molecular docking and molecular dynamics simulations. AB - Lysine-specific demethylase (LSD1) is an important enzyme for histone lysine methylation. Downregulated LSD1 expression has been linked to cancer proliferation, migration and invasion, indicating that it is an important target for anti-cancer medication. In the present study, the binding modes of a recent reported new series of LSD1 inhibitor were analyzed by using molecular docking and molecular dynamics simulations. A binding mode of these inhibitors was proposed based on the results. According to this binding mode, Thr628 can form two important hydrogen bonds with these inhibitors. Moreover, if the inhibitors can form an additional hydrogen bond with hydroxyl group of Ser289, the potency of the inhibitor can be greatly improved, such as the best inhibitor (compound 12d) in this series. Hydrophobic interactions between the inhibitors and LSD1 are also key contributor here, such as the interaction between the hydrophobic groups (benzene rings) of the inhibitors and the hydrophobic residues of LSD1 (including Val288, Val317, Val811, Ala814, Leu659, Trp751 and Tyr761). Based on the results and analysis, it may provide some useful information for future novel LSD1 inhibitor design. PMID- 26364658 TI - Perinatal outcomes with intrahepatic cholestasis of pregnancy in twin pregnancies. AB - OBJECTIVE: To describe perinatal outcomes of twin pregnancies complicated by intrahepatic cholestasis of pregnancy (ICP). METHODS: We conducted a retrospective cohort study of women delivered at a large tertiary obstetric center in Shanghai, China from January 2006 to May 2014. Delivery data were abstracted from medical records of all twin gestations delivered at the hospital. RESULTS: A total of 129/1922(6.7%) twin and 1190/92 273 singleton (1.3%) pregnancies were complicated by ICP. An increased risk of stillbirth among twin pregnancies was observed (3.9% and 0.8% in the ICP and non-ICP groups, respectively; aOR 5.75, 95% CI 2.00-16.6). Stillbirths with ICP and twins occurred between 33 and 35 weeks gestation compared to 36-38 weeks gestation among singletons. ICP in twins was also associated with an increased risk of preterm birth (<37 weeks) with an aOR of 4.17 (95% CI 2.47-7.04) and an aOR of 1.89 (95% CI 1.26-2.85) for delivery <35 weeks. Twin pregnancies complicated by ICP also had increased meconium staining of amniotic fluid and lower birth weight. CONCLUSIONS: Twin pregnancies with ICP have significantly increased risks of adverse perinatal outcomes including stillbirth and preterm birth. Stillbirth occurs at an earlier gestational age in twin gestation compared to singletons, suggesting that earlier scheduled delivery should be considered in these women. PMID- 26364659 TI - Asthma in schoolchildren in Monroe county, Florida: school-based needs assessment. AB - OBJECTIVES: Asthma is the most common chronic pediatric condition (14%) and the leading cause of school absenteeism in the USA. However, little is known about asthma prevalence and distribution in schoolchildren in the Florida Keys region (Monroe County). Thus, the objectives of this study were to assess asthma prevalence, symptoms, cost and distribution in schoolchildren in the Florida Keys region and to pinpoint where asthma management services are most needed. METHODS: Cross-sectional survey data on asthma prevalence, symptoms and socio-demographics was collected and analyzed by race, sex, grade and zip code. A total of 2313 parents of schoolchildren in the Florida Keys completed the adapted Harlem Empowerment Zone Asthma Initiative Questionnaire. The questionnaire was distributed to school principals, who sent them home with students to be filled out by parents or caregivers. We also analyzed data from the online Monroe County 2012 Florida Youth Tobacco Survey, the 2011 Florida CHARTS, the Medical Expenditures Panel Survey, and emergency departments (ED). Data were analyzed by race, sex, and grade. RESULTS: In total 14.5% of respondents had been told their child had asthma and 9.6% reported their child had wheezing in the last 12 months. The prevalence was higher in the Lower Keys and Key West regions. Parents from households where anyone smoked cigarettes (OR 1.52, 95% CI 1.11-2.09) and those who had a male child (1.53, 1.17-2.00) more often reported that their child had asthma. The rate of asthma-related ED visits for Black non-Hispanic schoolchildren (1202 per 100,000) was substantially higher than the numbers for White (250.2 per 100,000) and Hispanic schoolchildren (325.1 per 100,000). Most of the direct cost of asthma was concentrated in children in grades four through seven ($1236.02-$2147.02 per child). CONCLUSIONS: The asthma prevalence in a sample of schoolchildren in the Florida Keys region was comparable to the nationwide prevalence. Black non-Hispanic schoolchildren had more asthma-related ED visits that White and Hispanic schoolchildren. Most of the direct cost of asthma is concentrated in children in late elementary through early middle school grades. Interventions are needed, particularly targeting Black schoolchildren in late elementary through early middle school grades in Lower Keys and Key West region. PMID- 26364660 TI - Rosmarinic Acid Attenuates Sodium Taurocholate-Induced Acute Pancreatitis in Rats by Inhibiting Nuclear Factor-kappaB Activation. AB - Rosmarinic Acid (RA), a caffeic acid ester, has been shown to exert anti inflammation, anti-oxidant and antiallergic effects. Our study aimed to investigate the effect of RA in sodium taurocholate ( NaTC )-induced acute pancreatitis, both in vivo and in vitro. In vivo, RA (50 mg/kg) was administered intraperitoneally 2 h before sodium taurocholate injection. Rats were sacrificed 12 h, 24 h or 48 h after sodium taurocholate injection. Pretreatment with RA significantly ameliorated pancreas histopathological changes, decreased amylase and lipase activities in serum, lowered myeloperoxidase activity in the pancreas, reduced systematic and pancreatic interleukin-1 beta (IL-1beta), IL-6, and tumor necrosis factor-alpha (TNF-alpha) levels, and inhibited NF-kappaB translocation in pancreas. In vitro, pretreating the fresh rat pancreatic acinar cells with 80 MU mol/L RA 2 h before 3750 nmol/L sodium taurocholate or 10 ng/L TNF-alpha administration significantly attenuated the reduction of isolated pancreatic acinar cell viability and inhibited the nuclear activation and translocation of NF-kappaB. Based on our findings, RA appears to attenuate damage in sodium taurocholate-induced acute pancreatitis and reduce the release of inflammatory cytokines by inhibiting the activation of NF-kappaB. These findings might provide a basis for investigating the therapeutic role of RA in managing acute pancreatits. PMID- 26364661 TI - The Immunoregulatory Effects of Traditional Chinese Medicine on Treatment of Asthma or Asthmatic Inflammation. AB - Asthma is a chronic respiratory symptoms with variable airflow limitation and airway hyperresponsiveness (AHR), and causes high economic burden. Traditional Chinese medicine (TCM) has a long-lasting history of using herbal medicine in the treatment of various respiratory diseases including asthma. In the last several decades, an increasing number of herbs have been shown to be effective in the treatment of asthma in clinical trials or asthmatic inflammation in animal models. Literature about the effects of TCM on the immune system were searched in electronic databases such as PubMed, Google Scholar and Scopus from 2000 to 2014. 'TCM' and 'asthma' were used as keywords for the searches. Over 400 literatures were searched and the literatures about the immune system were selected and reviewed. We only reviewed literatures published in English. Accumulating evidence suggests that TCM can directly inhibit the activation and migration of inflammatory cells, regulate the balance of Th1/Th2 responses, and suppress allergic hyperreactivity through inducing regulatory T cells or attenuating the function of dendritic cells (DCs). These studies provided useful information to facilitate the use of TCM to treat asthma. This review was conducted to classify the findings based on their possible mechanisms of action reported. PMID- 26364662 TI - Icaritin Attenuates Myocardial Ischemia and Reperfusion Injury Via Anti Inflammatory and Anti-Oxidative Stress Effects in Rats. AB - Icaritin (ICT) is a traditional Chinese medicinal herb proved to be neuroprotective and exerts promoting effects on cardiac differentiation. However, its role in cardioprotection against myocardial ischemia/reperfusion (MI/R) injury remains largely unknown. This study aimed to investigate the effects of ICT treatment on MI/R injury and the underlying mechanisms. Rats were subjected to 30 min of myocardial ischemic insult followed by 3 h of reperfusion. ICT (3, 10, and 30 mg/kg) was administered intraperitoneally 10 min before reperfusion. ICT treatment at the dose of 10 and 30 mg/kg improved cardiac function and limited infarct size following MI/R. Meanwhile, ICT reduced plasma creatine kinase (CK), lactate dehydrogenase (LDH) activities and cardiomyocyte apoptosis in I/R heart tissue. Moreover, ICT treatment not only inhibited the pro inflammatory cytokine TNF-alpha production and increased the anti-inflammatory cytokine IL-10 level in myocardium but also reduced the increase in the generation of superoxide content and malondialdehyde (MDA) formation and simultaneously increased the anti-oxidant capability in I/R hearts. Furthermore, ICT treatment increased Akt phosphorylation and inhibited PTEN expression in I/R hearts. PI3K inhibitor wortmannin inhibited ICT-enhanced Akt phosphorylation, and blunted ICT-mediated anti-oxidative and anti-inflammatory effects and cardioprotection. Our study indicated for the first time that ICT reduces inflammation and oxidative stress and protects against MI/R injury in rats, which might be via a PI3K-Akt-dependent mechanism. PMID- 26364663 TI - Anti-Neuroinflammatory Effects of Uncaria sinensis in LPS-Stimulated BV2 Microglia Cells and Focal Cerebral Ischemic Mice. AB - Uncaria sinensis (US) has long been used as a traditional Korean medicine to treat cardiovascular and central nervous system diseases, including hypertension and cerebral ischemia. Several recent studies have indicated that US has neuroprotective and cerebrovascular protective effects in ischemic brain injury; however, little is known about the anti-inflammatory effects of US. Therefore, the present study was designed to validate the anti-inflammatory effects of US. The anti-neuroinflammatory properties of US on pro-inflammatory mediators were investigated in lipopolysaccharide (LPS)-stimulated murine BV2 microglia and injured brains induced by photothrombotic cortical ischemia. Hexane extracts of US (HEUS) significantly suppressed the production of nitric oxide (NO) and prostaglandin E2 (PGE2) in LPS-stimulated BV2 microglia and inhibited LPS-induced expression of iNOS and COX-2 in a dose-dependent manner without causing cytotoxicity in BV2 cells. In addition, HEUS significantly reduced the generation of pro-inflammatory cytokines, including TNF-alpha, IL-1beta, and IL-6. Moreover, HEUS treatment inhibited the transcriptional activity and nuclear translocation of NF-kappaB in LPS-stimulated BV2 cells. In an in vivo study, treatment of HEUS resulted in significantly reduced infarct volume and improved neurological function 48 h after ischemic brain injury, possibly through the inhibition of the production of pro-inflammatory cytokines. HEUS inhibits LPS-stimulated production of pro-inflammatory mediators and prevents cerebral ischemic damage, suggesting that US may have therapeutic potential for the prevention and treatment of ischemic stroke accompanied by microglia activation. PMID- 26364664 TI - Physical and anthropometric changes during pre- and in-season in professional soccer players. AB - BACKGROUND: The purpose of this study was to examine the changes in anthropometric and physical fitness characteristics in professional soccer players at the beginning of the season, after preseason camp and during in season. METHODS: Seventeen players were evaluated on three different periods (June: T0, August: T1 and December: T2). Each evaluation consisted of anthropometric measurements (body mass, height, and body fat) and physical fitness tests (counter movement jump [CMJ], counter movement jump with arm (CMJA), 10-m sprint, 30-m sprint and maximal aerobic speed [MAS]). RESULTS: Comparatively with T0, all physical performances achieved in T1 were significantly improved (MAS: P<0.01, 10-m sprint: P<0.05, 30-m sprint: P<0.05, CMJ: P<0.01, and CMJA: P<0.05). The decrease in training load during in-season is associated by significant decrement in MAS (P<0.05) and preserved performances in 10 (P=0.85) and 30-m sprint (P=0.99), CMJ (P=0.34) and CMJA (P=0.87) completed in T2 comparatively with T1. Physical fitness performances achieved in T2 remain higher than that obtained in T0 (MAS: P<0.01, 10-m sprint: P<0.01, 30-m sprint: P<0.05 and CMJ: P<0.05) and remain similar for CMJA (P=0.13). No significant changes were observed in anthropometric measurements throughout the study. CONCLUSIONS: The main finding of this study was that a greater training load accomplished during preseason could lead to an improvement in the physical fitness during in-season in professional soccer players. We suggest that this higher training load meets the needed required for the professional soccer although the training loads are declined during in-season. PMID- 26364665 TI - Physiological stress and performance analysis to karate combat. AB - BACKGROUND: This study aimed to evaluate the relationship between physiological, and parameters of performance analysis during karate contest. METHODS: Nine elite level karate athletes participated in this study. Saliva sample was collected pre and post-karate combat. RESULTS: Salivary cortisol (sC) post-combat 2 raised significantly compared to that recorded at pre-combat 1 (Delta%=105.3%; P=0.04; dz=0.78). The largest decrease of the salivary T/C ratio (sR) compared to pre combat 1 was recorded post-combat 2 (Delta%=-43.5%; P=0.03). Moreover, blood lactate concentration post-combat 1 correlated positively to sCpost-combat 1 (r=0.66; P=0.05) and negatively to both salivary testosterone (sT) (r=-0.76; P=0.01) and sRpost-combat 1 (r=-0.76; P=0.01). There was no significant relationship between hormonal measures and parameters of match analysis. CONCLUSIONS: Although under simulated condition, karate combat poses large physiological stress to the karateka. Additionally, physiological strain to karate combat led to a catabolic hormonal response. PMID- 26364666 TI - Preparing patients with cancer who work and treatment responsiveness. AB - BACKGROUND: Many patients with life-limiting illnesses continue to work because of financial reasons and because work provides good psychosocial support. A lack of appropriate advice/support through patient education could, however, make having a job detrimental to well-being (eg, symptom worsening). AIM: This study investigated the frequency with which patients received information that empowers their understanding of their condition, treatment, side effects of treatment and the likely impact on occupational functioning. DESIGN: A cross-sectional study. SETTING/PARTICIPANTS: An analysis of survey data from 3457 patients with cancer in employment. RESULTS: Logistic regression showed that patients who received information about the impact of cancer on work life or education are 1.72 times more likely to have a positive treatment outcome. Patients who receive written information about the type of cancer are 1.99 times more likely to have a positive treatment outcome. Also, patients who receive written information before a cancer-related operation are 1.90 times more likely to have a positive treatment outcome. Information about the side effects of cancer treatment produces worse odds of a positive treatment outcome (0.65-1). A stepwise logistic regression analysing the effects irrespective of current employment status in 6710 patients showed that preparing them produces nearly twice better odds of cancer treatment responsiveness. CONCLUSIONS: Palliative care teams should consider ways of actively advising patients who work. Whereas the results showed evidence of good practice in cancer care, there is a need to ensure that all working patients with potentially life-limiting illnesses receive similar support. PMID- 26364667 TI - A comparison between the two methods of magnesium sulfate administration for duration of 12 versus 24 h after delivery in patients with severe preeclampsia. AB - OBJECTIVES: To compare between the two methods of magnesium sulfate administration for duration of 12 versus 24 h after delivery in patients with severe preeclampsia. METHOD: The study was performed as a randomized clinical trial on 182 cases of severe preeclampsia. In one group, Mg sulfate (MgSO4) was prescribed for 12 h after delivery and, in the other group, it was prescribed for 24 h after delivery. Both groups were compared for occurrence of convulsion and other adverse effects. RESULTS: The women of the two groups did not have significant difference according to age, BMI, parity and gravidity, gestational age at the time of delivery. Also, systolic blood pressure, diastolic blood pressure, antihypertensive use, previous diabetes and renal disorders, gestational diabetes, and proteinuria were similar in both groups before treatment. One woman had convulsion in the 12-h group and MgSO4 was continued for 24 h in this case. Blood pressure, urine volume, and laboratory indexes did not show significant differences between the two groups before and after treatment. Also, adverse effects were similar in both groups. Pain of the injection site was less in the 12-h group (p = 0.048). CONCLUSION: Administration of MgSO4 for a duration of 12 h after delivery should be considered somehow as effective as 24 h prescription for preventing convulsion after delivery. PMID- 26364668 TI - Comments on "Evaluation Indexes of Military Hospitals From the Experts' Perspective: A Qualitative Study". PMID- 26364669 TI - Finding smORFs: getting closer. AB - Millions of small open reading frames exist in eukaryotes. We do not know how many, or which are translated, but bioinformatics is getting us closer to the answer. See related Research article: http://www.genomebiology.com/2015/16/1/179. PMID- 26364671 TI - Prescribing of neuraminidase inhibitors for influenza in UK primary care since the 2009 pandemic. AB - We determined prescribing rates of neuraminidase inhibitors (NIs) for influenza in UK primary care since 2009 in relation to national prescribing guidelines. All NI prescriptions issued during the influenza seasons between October 2010 and May 2013 were extracted from The Health Improvement Network (THIN), a large UK primary-care database. We calculated NI prescribing rates per 100,000 person weeks (pw) by age group, sex, deprivation level, influenza season and presence of chronic conditions with 95% confidence intervals (CIs), and used negative binomial regression models to determine the independent association between these variables and NI prescribing. NI prescribing was rare. The prescribing rate was 1.7/100,000 pw (95% CI 1.7-1.8) during influenza-active periods, and 0.1/100,000 (95% CI 0.1-0.1) during non-active periods. Prescribing rates were highest in 25- to 44-year-olds in 2010/2011 and in persons aged ?85 years in 2011/2012 and 2012/2013. Individuals with chronic conditions had significantly higher prescribing rates than persons without (rate ratio 2.62, 95% CI 2.27-3.03). GPs are more likely to prescribe NIs to high-risk individuals and during influenza active periods, as per national guidelines. We could not assess the proportion of patients with influenza-like illness who were prescribed an NI. PMID- 26364670 TI - Regulation of the chitin degradation and utilization system by the ChiX small RNA in Serratia marcescens 2170. AB - Serratia marcescens 2170 produces three different types of chitinases and chitin binding protein CBP21. We found that transposon insertion into the 5' untranslated region (5' UTR) of chiPQ-ctb led to defective chitinase and CBP21 production. ChiX small RNA possessed the complementary sequence of the 5' UTRs of the chiPQ-ctb and chiR and repressed the expression of chiP and chiR. ChiX was detected in a medium containing glucose, glycerol, GlcNAc, and (GlcNAc)2, but the expression of both chiP and chiR was only observed in a medium containing (GlcNAc)2. ?chiX mutant produced chitinases, CBP21, and chitobiase without induction. chiP transcripts were more abundant than those of chiR or chiX in a medium containing (GlcNAc)2. These results suggest that the constitutively expressed ChiX binds to the highly abundant chiP 5' UTR, thereby leading to the induction of chiR mRNA translation and the subsequent expression of chitinases and CBP21. PMID- 26364672 TI - Integrating Frailty Assessment Into Cardiovascular Decision Making. PMID- 26364673 TI - Class Anxiety in Secondary Education: Exploring Structural Relations with Perceived Control, Engagement, Disaffection, and Performance. AB - The aim of this study was to assess the relationships between class-related anxiety with perceived control, teacher-reported behavioral engagement, behavioral disaffection, and academic performance. Participants were 355 compulsory secondary students (9th and 10th grades; Mean age = 15.2 years; SD = 1.8 years). Structural equation models revealed performance was predicted by perceived control, anxiety, disaffection, and engagement. Perceived control predicted anxiety, disaffection, and engagement. Anxiety predicted disaffection and engagement, and partially mediated the effects from control on disaffection (beta = -.277, p < .005; CI = -.378, -.197) and engagement (beta = .170, p < .002; CI = .103 .258). The negative association between anxiety and performance was mediated by engagement and disaffection (beta = -.295, p < .002; CI = -.439, .182). Anxiety, engagement, and disaffection mediated the effects of control on performance (beta = .352, p < .003; CI = .279, .440). The implications of these results are discussed in the light of current theory and educational interventions. PMID- 26364674 TI - Proteomics studies on stress responses in diatoms. AB - Diatoms are a highly diverse group of eukaryotic phytoplankton that are distributed throughout marine and freshwater environments and are believed to be responsible for approximately 40% of the total marine primary productivity. The ecological success of diatoms suggests that they have developed a range of strategies to cope with various biotic and abiotic stress factors. It is of great interest to understand the adaptive responses of diatoms to different stresses in the marine environment. Proteomic technologies have been applied to the adaptive responses of marine diatoms under different growth conditions in recent years such as nitrogen starvation, iron limitation and phosphorus deficiency. These studies have provided clues to elucidate the sophisticated sensing mechanisms that control their adaptive responses. Although only a very limited number of proteomic studies were conducted in diatoms, the obtained data have led to a better understanding of the biochemical processes that contribute to their ecological success. This review presents the current status of proteomic studies of diatom stress responses and discusses the novel developments and applications for the analysis of protein post-translational modification in diatoms. The potential future application of proteomics could contribute to a better understanding of the physiological mechanisms underlying diatom acclimation to a given stress and the acquisition of an enhanced diatom stress tolerance. Future challenges and research opportunities in the proteomics studies of diatoms are also discussed. PMID- 26364675 TI - Drug Use in the Twittersphere: A Qualitative Contextual Analysis of Tweets About Prescription Drugs. AB - Tweets about prescription opioid use may reveal insights into the prescription drug epidemic. We qualitatively assessed 2,100 tweets about prescription opioids utilizing a Twitter Archiving Google Spreadsheet(r) and determined whether the tweet represented: abuse (i.e., use to get high), not abuse (i.e., use as analgesic), or was not characterizable (e.g., "I need a Percocet") and whether the connotation was positive (i.e. promote psychoactive or analgesic use), negative (i.e., adverse event), or not characterizable. Abuse was commonly described and the majority of terms (>66%) represented a positive connotation. Twitter can be a resource to observe trends in perceptions about prescription opioid use. PMID- 26364676 TI - Gradient echo single scan inversion recovery: application to proton and fluorine relaxation studies. AB - Single scan longitudinal relaxation measurement experiments enable rapid estimation of the spin-lattice relaxation time (T1 ) as the time series of spin relaxation is encoded spatially in the sample at different slices resulting in an order of magnitude saving in time. We consider here a single scan inversion recovery pulse sequence that incorporates a gradient echo sequence. The proposed pulse sequence provides spectra with significantly enhanced signal to noise ratio leading to an accurate estimation of T1 values. The method is applicable for measuring a range of T1 values, thus indicating the possibility of routine use of the method for several systems. A comparative study of different single scan methods currently available is presented, and the advantage of the proposed sequence is highlighted. The possibility of the use of the method for the study of cross-correlation effects for the case of fluorine in a single shot is also demonstrated. PMID- 26364677 TI - Theoretical analysis of NMR shieldings of group-11 metal halides on MX (M = Cu, Ag, Au; X = H, F, Cl, Br, I) molecular systems, and the appearance of quasi instabilities on AuF. AB - Accurate calculations of nuclear magnetic shieldings of group-11 metal halides, sigma(M; MX) (M = Cu, Ag, Au; X = H, F, Cl, Br, I), were performed with relativistic and nonrelativistic theoretical schemes in order to learn more about the importance of the involved electronic mechanisms that underlie such shieldings. We applied state of the art schemes: polarization propagators at a random phase level of approach (PP-RPA); spin-free Hamiltonian (SF); linear response elimination of small component (LRESC) and density functional theory (DFT) with two different functionals: B3LYP and PBE0. The results from DFT calculations are not close to those from the relativistic polarization propagator calculations at the RPA level of approach (RelPP-RPA), in line with previous results. The spin-orbit (SO) contribution to a shielding constant is important only for MF molecules (M = Cu, Ag, Au). Different electronic mechanisms are considered within the LRESC method, bunched into two groups: core- and ligand dependent. For the analysed shieldings the core-dependent electronic mechanisms are the most important ones; the ligand-dependent being only important for MF molecules. An out of range value for sigma(Au) is found in AuF. It was previously reported in the literature, either originated in the large fluorine electronegativity together with large spin-orbit coupling contributions; or, due to Fermi-contact contributions. We argue here that such an unexpected large value is an artifact originated in the appearance of quasi instabilities, and show how to handle this apparent problem. PMID- 26364678 TI - Asymmetric dimethylarginine but not osteoprotegerin correlates with disease severity in patients with moderate-to-severe psoriasis undergoing anti-tumor necrosis factor-alpha therapy. AB - Patients with psoriasis, in particular those with severe disease, have an increased risk of cardiovascular (CV) events compared with the general population. The aim of the present study is to determine whether correlation between asymmetric dimethylarginine (ADMA) and osteoprotegerin (OPG), two biomarkers associated with CV disease, and disease severity may exist in patients with moderate-to-severe psoriasis. We also aimed to establish if baseline serum levels of these two biomarkers could correlate with the degree of change in the clinical parameters of disease severity following the use of anti-tumor necrosis factor (TNF)-alpha therapy in these patients. This was a prospective study on a series of consecutive non-diabetic patients with moderate-to-severe psoriasis who completed 6 months of therapy with anti-TNF-alpha-adalimumab. Patients with kidney disease, hypertension or body mass index of 35 kg/m(2) or more were excluded. Metabolic and clinical evaluation was performed immediately prior to the onset of treatment and at month 6. Twenty-nine patients were assessed. Unlike OPG, a significant positive correlation between ADMA and resistin serum levels was found at the onset of adalimumab and also after 6 months of biologic therapy. We also observed a positive correlation between the percent of body surface area affected (BSA) and ADMA levels obtained before the onset of adalimumab and a negative correlation between baseline ADMA levels and a 6-month BSA change compared with baseline results. In patients with moderate-to-severe psoriasis, ADMA levels correlate with clinical markers of disease severity. PMID- 26364679 TI - Cost Analysis of Endoscopic Mucosal Resection vs Surgery for Large Laterally Spreading Colorectal Lesions. AB - BACKGROUND & AIMS: Large laterally spreading lesions (LSL) in the colon and rectum can be safely and effectively removed by endoscopic mucosal resection (EMR). However, many patients still undergo surgery. Endoscopic treatment may be more cost effective. We compared the costs of endoscopic versus surgical management of large LSL. METHODS: We performed a prospective, observational, multicenter study of consecutive patients referred to 1 of 7 academic hospitals in Australia for the management of large LSL (>= 20 mm) from January 2010 to December 2013. We collected data on numbers of patients undergoing EMR, actual endoscopic management costs (index colonoscopy, hospital stay, adverse events, and first surveillance colonoscopy), characteristics of patients and lesions, outcomes, and adverse events, and findings from follow-up examinations 14 days, 4 6 months, and 16-18 months after treatment. We compared data from patients who underwent EMR with those from a model in which all patients underwent surgery without any complications. Event-specific costs, based on Australian refined diagnosis-related group codes, were used to estimate average cost per patient. RESULTS: EMR was performed on 1489 lesions (mean size, 36 mm) in 1353 patients (mean age, 67 years; 52.1% male). Total costs involved in the endoscopic management of large LSL were US $6,316,593 and total inpatient hospitalization length of stay was 1180 days. The total cost predicted for the surgical management group was US $16,601,502, with a total inpatient hospitalization length of stay of 4986 days. Endoscopic management produced a potential total cost saving of US $10,284,909; the mean cost difference per patient was US $7602 (95% confidence interval, $8458-$9220; P < .001). Inpatient hospitalization length of stay was reduced by 2.81 nights per patient (95% confidence interval, 2.69-2.94; P < .001). CONCLUSIONS: In a large multicenter study, endoscopic management of large LSL by EMR was significantly more cost-effective than surgery. Endoscopic management by EMR at an appropriately experienced and resourced tertiary center should be considered the first line of therapy for most patients with this disorder. This approach is likely to deliver substantial overall health expenditure savings. ClinicalTrials.gov, Number: NCT01368289. PMID- 26364680 TI - Topological Linkage of DNA Tiles Bonded by Paranemic Cohesion. AB - Catenation is the process by which cyclic strands are combined like the links of a chain, whereas knotting changes the linking properties of a single strand. In the cell, topoisomerases catalyzing strand passage operations enable the knotting and catenation of DNA so that single- or double-stranded segments can be passed through each other. Here, we use a system of closed DNA structures involving a paranemic motif, called PX-DNA, to bind double strands of DNA together. These PX cohesive closed molecules contain complementary loops whose linking by Escherichia coli topoisomerase 1 (Topo 1) leads to various types of catenated and knotted structures. We were able to obtain specific DNA topological constructs by varying the lengths of the complementary tracts between the complementary loops. The formation of the structures was analyzed by denaturing gel electrophoresis, and the various topologies of the constructs were characterized using the program Knotilus. PMID- 26364681 TI - Proteomic profiling of gill GSTs in Mytilus galloprovincialis from the North of Portugal and Galicia evidences variations at protein isoform level with a possible relation with water quality. AB - Glutathione transferases (GSTs) are key for xenobiotic detoxification at the molecular level across phyla. These enzymes are therefore likely to be part of the defence mechanisms used by marine organisms, such as mussels, that thrive in highly polluted environments. Taking this hypothesis into account, we used proteomics to characterize the profile of GSTs from the gills of marine mussel Mytilus galloprovincialis in order to discriminate natural mussel populations exposed to different levels of pollution. Samples were collected between Cabo Home (Spain) and Matosinhos (Portugal) covering a north-south transect of approximately 122 Km of the Atlantic Ocean along the Western Coast of the Iberian Peninsula. GSTs from mussel gills were extracted and purified by affinity chromatography with glutathione as the binding substrate to the solid medium. We studied the abundance of GST isoforms by two-dimensional gel electrophoresis and matrix assisted laser desorption/ionization-time of flight mass spectrometry and assessed total activity. Eleven putative individual GSTs from classes Mu, Pi and Sigma were identified by proteomics. Few variations were observed in total GST activity of post-mitochondrial samples between sampling sites, with animals from Matosinhos (polluted site) showing highest GST activity and Cabo Home (clean site) showing lowest. This contrasts with the increased number of differences in the individual GST isoforms. Each mussel population showed unique GST proteomic profiles. Based on the results we conclude that proteomics surpasses the conventional GST enzymatic activity method to discriminate natural mussel populations and has potential application in environmental monitoring. It is reasonable to suggest that the GST proteomic profiles observed may reflect differences in contamination levels. PMID- 26364682 TI - Histopathological baseline levels and confounding factors in common sole (Solea solea) for marine environmental risk assessment. AB - Liver and gonad histopathology, biometric parameters and hepatic metal bioaccumulation were assessed monthly over a one-year period in common soles from the Basque continental shelf, in order to determine baseline levels and confounding factors within biomonitoring studies. Biometric parameters and hepatic metal bioaccumulation varied according to season and gender. Accordingly, hepatic histopathological traits presented seasonal variations related to the reproductive cycle. However, the hepatic histopathological index showed that seasonality and gender were not significant confounding factors. Conversely, the gonad histopathological index was modulated by season and gender. As for organ comparison, the liver endured more severe histopathological damage than the gonad. In brief, the sampling period and gender may not affect the estimation of hepatic histopathological indices for biomonitoring purposes. Nonetheless, due to different sensitivities to environmental 'noise' variables, the sampling period and gender differentiation should be thoroughly considered for the assessment of gonad histopathology, biometrics and metal bioaccumulation. PMID- 26364684 TI - Life-threatening hemorrhage associated with dental implant surgery: a review of the literature. AB - OBJECTIVES: Life-threatening bleeding may occur during implant placement. PURPOSE: The present review was conducted to evaluate the localization, the symptoms, and therapies of life-threatening bleedings associated with implant placement. MATERIAL AND METHODS: A literature review including 590 articles was performed in PubMed, Medline, and Cochrane database. Any article reporting on life-threatening bleeding was included which additionally reported on the site of implant surgery. RESULTS: Twenty-seven cases were extracted. In the majority of the cases, bleeding occurred in the anterior interforaminal region. Aside local management stopping the bleedings, most cases required intubation or tracheotomy. CONCLUSIONS: Surgeons must be aware of the risk of severe bleedings during implant surgery and should immediately refer patients to a specialized clinic in suspicious or proved cases. PMID- 26364683 TI - Aliens in Paradise. Boat density and exotic coastal mollusks in Moorea Island (French Polynesia). AB - Pacific islands are particularly vulnerable to the effects of invasive species. After habitat destruction or modification, invasive species are responsible for more biological extinctions than any other cause. Further, the rate of extinction of native species has been higher on islands than anywhere else in the world. Invasive species have also degraded native ecosystems. In order to detect exotic intertidal mollusk species, an extensive sampling around Moorea Island, a more or less unspoiled island surrounded by a rich coral reef habitat, has been developed considering that sampled points have different characteristics in wave exposure, algae coverage, type of substrate, distance to ports, distance to freshwater, distance sewage and boat traffic. Samples were DNA barcoded for unequivocal species assignation. The presence of five NIS among 26 species seems an important signal of introduction of alien biota in Moorea Island coast. However they were represented by a total of 38 individuals among 1487 mollusks (2.55%). While the distance to relatively big ports influenced directly species richness, the intensity of maritime traffic measured as boat density near sampling points was significantly associated with the frequency of exotic species. Other environmental factors did not show significant correlation with the frequency of exotics, suggesting that in an environment without big discontinuities, with little habitat modification, local boat traffic is the most influential factor in the spread of exotic species. This could be mitigated relatively easily by reducing boat density in local zones of ecological interest. PMID- 26364685 TI - Freeze-drying of live virus vaccines: A review. AB - Freeze-drying is the preferred method for stabilizing live, attenuated virus vaccines. After decades of research on several aspects of the process like the stabilization and destabilization mechanisms of the live, attenuated viruses during freeze-drying, the optimal formulation components and process settings are still matter of research. The molecular complexity of live, attenuated viruses, the multiple destabilization pathways and the lack of analytical techniques allowing the measurement of physicochemical changes in the antigen's structure during and after freeze-drying mean that they form a particular lyophilization challenge. The purpose of this review is to overview the available information on the development of the freeze-drying process of live, attenuated virus vaccines, herewith focusing on the freezing and drying stresses the viruses can undergo during processing as well as on the mechanisms and strategies (formulation and process) that are used to stabilize them during freeze-drying. PMID- 26364686 TI - Low load, high repetition resistance training program increases bone mineral density in untrained adults. AB - BACKGROUND: High load, low repetition resistance training increases BMD in untrained adults; however, many older and untrained adults cannot maintain this type of strenuous program. Our goal was to evaluate whether a low load, high repetition resistance training program would increase BMD in untrained adults. METHODS: Twenty sedentary, but otherwise healthy, adults (6 men and 14 women, age 28-63 yrs) completed a 27-week group exercise program. The participants were randomly assigned to one of two strength groups: one group completed full body, low load, high repetition weight training classes (S-WEIGHT), while the other group completed core focused fusion classes (S-CORE). Both groups also completed indoor cycling classes for cardiovascular conditioning. After a 3-week familiarization period, all participants completed a 12-week block of 5 fitness classes per week (3 cycling + 2 strength) and concluded with another 12-week block of 6 classes per week (3 cycling + 3 strength). We completed iDXA scans at baseline (week 3) and final (week 28). RESULTS: Compared to baseline, BMD significantly increased for S-WEIGHT in the arms (+4%, P<0.001), legs (+8%, P<0.01), pelvis (+6%, P<0.01) and lumbar spine (+4%, P<0.05), whereas BMD did not significantly change for S-CORE at any site. CONCLUSIONS: These results suggest that a low load, high repetition resistance training program may be an effective method to improve bone mass in adults. PMID- 26364687 TI - Kinetic analysis of the function of the upper body for elite race walkers during official men 20 km walking race. AB - BACKGROUND: This study investigated the function of the upper extremities of elite race walkers during official 20 km races, focusing on the angular momentum about the vertical axis and other parameters of the upper extremities. METHODS: Sixteen walkers were analysed using the three-dimensional direct linear transformation method during three official men's 20 km walking races. The subjects, included participants at the Olympics and World Championships, who finished without disqualification and had not been disqualified during the two years prior to or following the races analysed in the present study. RESULTS: The angular momenta of the upper and lower body were counterbalanced as in running and normal walking. The momentum of the upper body was mainly generated by the upper extremities. The joint force moment of the right shoulder and the joint torque at the left shoulder just before right toe-off were significantly correlated with the walking speed. These were counterbalanced by other moments and torques to the torso torque, which worked to obtain a large mechanical energy flow from the recovery leg to the support leg in the final phase of the support phase. CONCLUSIONS: Therefore, a function of the shoulder torque was to counterbalance the torso torque to gain a fast walking speed with substantial mechanical energy flow. PMID- 26364688 TI - Influence of recovery intensity on oxygen demand and repeated sprint performance. AB - BACKGROUND: This study aimed to determine effects of recovery intensity (passive, 20%, 30% and 40% VO2peak) on oxygen uptake kinetics, performance and blood lactate accumulation during repeated sprints. METHODS: Seven moderately-trained male participants (VO2peak: 48.1+/-5.1 mL/kg/min) performed four 30-second repeated Wingate tests on four separate occasions. RESULTS: Recovery of VO2 between sprints was prolonged with recovery intensity (time required to reach 50% VO2peak: passive: 50+/-9 s; 20%: 81+/-17 s; 30%: 130+/-43 s; 40%: 188+/-62 s, P<0.001), while VO2-to-sprint work ratio was mainly increased by the higher intensities (passive: 138+/-17 mL/min/kJ; 20%: 149+/-14 mL/min/kJ; 30%: 159+/-15 mL/min/kJ; 40%: 158+/-17 mL/min/kJ, P=0.001). The decline in peak power tended to be greater in the higher intensity conditions during sprint 2 (passive: 7.4+/ 5.4%; 20%: 5.8+/-7.9%; 30%: 12.7+/-7.4%; 40%: 12.7+/-5.5%, P=0.052), whereas average power was less decreased with recovery intensity during sprint 4 (passive: 22.4+/-8.9%; 20%: 19.9+/-6.1%; 30%: 18.4+/-7.3%; 40%: 16.6+/-6.2%, P=0.036). Blood lactate was not different with recovery intensity (P=0.251). CONCLUSIONS: The present study demonstrated that while the higher recovery intensities induce prolonged oxygen recovery and impaired peak power restoration during the initial sprints, those intensities provide a greater aerobic contribution to sprint performance, resulting in better power maintenance during the latter sprints. PMID- 26364689 TI - Exercise training at the crossover point improves bodily and cardiorespiratory data but not quality of life in women with metabolic syndrome. AB - BACKGROUND: This study investigated the effects of an exercise program at the intensity corresponding to the crossover point of substrate utilization (COP) on anthropometric measures, health-related quality of life (HRQoL) and cardiorespiratory fitness (i.e., peak oxygen uptake [VO2peak] and peak power output [Ppeak]) in women with metabolic syndrome (MetS). METHODS: Nineteen obese and post-menopausal women with MetS (age: 54.8+/-8.1 years, body mass: 89.0+/ 12.2 kg, Body Mass Index: 34.5+/-4.0 kg/m2) followed a 12-week program consisting of three 45-minute sessions per week of cycle ergometer exercise. The imposed exercise intensity corresponded to COP. Before and after the program, HRQoL, VO2peak and Ppeak were measured and then compared. RESULTS: Body mass (89.0+/ 12.2 vs. 86.2+/-11.0 kg), Body Mass Index (34.5+/-4.0 vs. 33.4+/-3.6 kg/m2), waist (106+/-10 vs. 100+/-9 cm) and hip (117+/-11 vs. 114+/-11 cm) circumferences, waist-to-hip ratio (0.91+/-0.07 vs. 0.88+/-0.07), fat mass (43.3+/-4.6 vs. 41.9+/-4.6%), fat-free mass (56.7+/-4.6 vs. 58.2+/-4.6%), VO2peak (16.6+/-3.4 vs. 18.1+/-4.1 mL/min/kg) and Ppeak (102+/-22 vs. 125+/-27 W) were significantly improved after the exercise program (P<0.05), but HRQoL showed no significant improvement on any subscale (i.e., physical functioning: performance limitation for physical activities including bathing and dressing, role physical: problems with work or other daily activities, bodily pain, general health, vitality, social functioning, role emotional and mental health; P>0.05). CONCLUSIONS: Although a 12-week exercise program at COP improved anthropometric measures and cardiorespiratory fitness in women with MetS, self-perceived HRQoL did not significantly improve. This finding may be linked to a significant but still insufficient reduction in body mass, probably because COP is too weak exercise intensity to induce important energy expenditure. PMID- 26364690 TI - Effects of a Whatsapp-delivered physical activity intervention to enhance health related physical fitness components and cardiovascular disease risk factors in older adults. AB - BACKGROUND: This pilot study evaluated the feasibility and preliminary effectiveness of a 10-week WhatsApp-based intervention aimed at enhancing health related physical fitness components and cardiovascular disease (CVD) risk factors compared with a face-to-face condition. METHODS: Participants (N.=32) were assigned to one of three groups: training group (N.=16), mobile group (N.=7) and control group (N.=9). Training group and mobile group performed the same training program, based on strength training with elastics bands and aerobic exercise, during 10 weeks; only the delivery mode differed. RESULTS: The mobile group increased handgrip strength, aerobic capacity and decreased systolic blood pressure and heart rate after exercise though there were no significant differences respect to control group. The training group decreased significantly systolic blood pressure (P=0.038), diastolic blood pressure (P=0.005), mean arterial pressure (P=0.006) and heart rate after exercise (P=0.002), respect to control group. CONCLUSIONS: Comparison between training and mobile group showed that WhatsApp-based physical activity intervention was less effective than face to-face condition. The results indicate that the use of an online social network produced slight changes in some health-related physical fitness components and CVD risk factors. PMID- 26364691 TI - Clinical and computed tomography tumour dimension assessments for planning wide excision of injection site sarcomas in cats: how strong is the agreement? AB - In injection site sarcoma (ISS) in cats lateral as well as deep margins should be correctly planned for a successful surgical outcome. The discrepancy between clinical and computed tomography (CT) measurements of dimension in resectable tumour has led to possible bias that affects the subsequent surgical dose. The aim of this study was to prospectively investigate the agreement between clinical and CT measurements of dimension in newly diagnosed ISS in cats. Fifty-three client-owned cats that underwent both clinical and CT measurements of the length and width of ISS were included. CT measurements showed a tendency towards being larger than clinical dimensions, and this difference increased with increasing tumour size. Based on our results, in further studies focusing on ISS in cats, the kind of assessment used to define tumour dimensions (CT versus clinic) should be declared and specified to properly consider surgical results and prognostic impact of this variable. PMID- 26364692 TI - Vagus Nerve and Vagus Nerve Stimulation, a Comprehensive Review: Part I. AB - The vagus nerve (VN), the "great wondering protector" of the body, comprises an intricate neuro-endocrine-immune network that maintains homeostasis. With reciprocal neural connections to multiple brain regions, the VN serves as a control center that integrates interoceptive information and responds with appropriate adaptive modulatory feedbacks. While most VN fibers are unmyelinated C-fibers from the visceral organs, myelinated A- and B-fiber play an important role in somatic sensory, motor, and parasympathetic innervation. VN fibers are primarily cholinergic but other noncholinergic nonadrenergic neurotransmitters are also involved. VN has four vagal nuclei that provide critical controls to the cardiovascular, respiratory, and alimentary systems. Latest studies revealed that VN is also involved in inflammation, mood, and pain regulation, all of which can be potentially modulated by vagus nerve stimulation (VNS). With a broad vagal neural network, VNS may exert a neuromodulatory effect to activate certain innate "protective" pathways for restoring health. PMID- 26364693 TI - Hypercaloric diet modulates effects of chronic stress: a behavioral and biometric study on rats. AB - Obesity is a chronic disease that has been associated with chronic stress and hypercaloric diet (HD) consumption. Increased ingestion of food containing sugar and fat ingredients (comfort food) is proposed to "compensate" chronic stress effects. However, this eating habit may increase body fat depositions leading to obesity. This study evaluated behavioral/physiological parameters seeking to establish whether there is an association between the effects of HD intake and stress, and to test the hypothesis that the development of anxious behavior and obesity during chronic stress periods depends on the type of diet. Sixty-day-old male Wistar rats (n = 100) were divided into four groups: standard chow, hypercaloric diet, chronic stress/standard chow and chronic stress/hypercaloric diet. Chronic stress was induced by restraint stress exposure for 1 h/day, for 80 d. At the end of this period, rat behavior was evaluated using open-field and plus-maze tests. The results showed that HD alone increased weight gain and adipose deposition in subcutaneous and mesenteric areas. However, stress reduced weight gain and adipose tissue in these areas. HD also increased naso-anal length and concurrent stress prevented this. Behavioral data indicated that stress increased anxiety-like behaviors and comfort food reduced these anxiogenic effects; locomotor activity increased in rats fed with HD. Furthermore, HD decreased corticosterone levels and stress increased adrenal weight. The data indicate that when rats are given HD and experience chronic stress this association reduces the pro-obesogenic effects of HD, and decreases adrenocortical activity. PMID- 26364696 TI - Dissipative particle dynamics simulation study on self-assembly of amphiphilic hyperbranched multiarm copolymers with different degrees of branching. AB - Hyperbranched multiarm copolymers (HMCs) have shown great potential to be excellent precursors in self-assembly to form various supramolecular structures in all scales and dimensions in solution. However, theoretical studies on the self-assembly of HMCs, especially the self-assembly dynamics and mechanisms, have been greatly lagging behind the experimental progress. Herein, we investigate the effect of degree of branching (DB) on the self-assembly structures of HMCs by dissipative particle dynamics (DPD) simulation. Our simulation results demonstrate that the self-assembly morphologies of HMCs can be changed from spherical micelles, wormlike micelles, to vesicles with the increase of DBs, which are qualitatively consistent with the experimental observations. In addition, both the self-assembly mechanisms and the dynamic processes for the formation of these three aggregates have been systematically disclosed through the simulations. These self-assembly details are difficult to be shown by experiments and are very useful to fully understand the self-assembly behaviors of HMCs. PMID- 26364695 TI - The Diagnostic and Prognostic Performance of Urinary FGFR3 Mutation Analysis in Bladder Cancer Surveillance: A Prospective Multicenter Study. AB - OBJECTIVE: To assess the diagnostic and prognostic performance of a noninvasive FGFR3 mutation analysis. After transurethral resection (TUR) of noninvasive bladder transitional cell carcinoma (B-TCC), recurrence occurs in 70% of patients, thus justifying cystoscopic surveillance. MATERIALS AND METHODS: A prospective multicenter study was carried out with a 2-year follow-up of patients with superficial B-TCC. Urine samples were collected before TUR and then before each cystoscopy during follow-up. Screening for the most prevalent FGFR3 mutations was done using urinary cells. The prognostic significance of an FGFR3 mutation at the time of the initial diagnosis was determined. The performance of the test in diagnosing and/or predicting recurrence during follow-up was assessed by calculating sensitivity and specificity. RESULTS: Of 191 patients studied, 74 (39%) had a positive analysis before TUR (FGFR3 mutation group). The presence of an FGFR3 mutation at the time of diagnosis was associated with a shorter time to recurrence (P = .02). During follow-up, 68 patients from the FGFR3 mutation group were evaluated. FGFR3 mutation analysis showed a sensitivity of 0.73 and a specificity of 0.87 when compared with the results of cystoscopy. A positive urine test was predictive of recurrence either at the time of the positive result or later during the 2-year follow-up, with a sensitivity of 0.70 and a specificity of 0.87. CONCLUSION: Among patients with an FGFR3 mutation in the initial tumor, a noninvasive urine test during follow-up can be valuable in diagnosing or predicting subsequent recurrence. PMID- 26364697 TI - A comprehensive guide to the surgical management of nonmelanoma skin cancer. PMID- 26364698 TI - Radiotherapy for management of basal and squamous cell carcinoma. PMID- 26364699 TI - Efficacy and Safety of Split Peroneal Tendon Lateral Ankle Stabilization. AB - Chronic lateral ankle instability is a common condition. Split peroneal tendon lateral ankle stabilization, a modification of the Chrisman-Snook procedure, is biomechanically stable and often used for severe and/or recurrent chronic lateral ankle instability. The purpose of the present study was to evaluate the efficacy and safety of this technique. Specifically, the midterm recurrence of instability and postoperative complications, such as stiffness, neurologic pain, and wound healing complications, were evaluated. We evaluated 30 consecutive procedures with a minimal follow-up period of 1 year. The mean follow-up period was 25 +/- 13 (median 19, range 13 to 62) months. Five patients (17%) developed recurrent ankle instability, of whom 4 underwent revision surgery. One superficial infection and two wound disruptions developed. Two patients experienced stiffness and eight (27%) surgically induced neurologic complaints, such as sural neuritis. Finally, 2 patients developed complex regional pain syndrome. PMID- 26364700 TI - Talar Fractures in Children: A Possible Injury After Go-Karting Accidents. AB - Go-karting is an increasingly popular high-energy sport enjoyed by both children and adults. Because of the speeds involved, accidents involving go-karts can lead to serious injury. We describe 6 talar fractures in 4 patients that resulted from go-karting accidents. Talar fractures can cause severe damage to the tibiotalar joint, talocalcaneal or subtalar joint, and the talonavicular joint. This damage can, in turn, lead to complications such as avascular necrosis, arthritis, nonunion, delayed union, and neuropraxia, which have the potential to cause long term disability in a child. PMID- 26364701 TI - Antibiotic Prophylaxis in Adults With Open Tibial Fractures: What Is the Evidence for Duration of Administration? A Systematic Review. AB - Open tibial fractures are common injuries after high-energy trauma such as road traffic accidents. Infection is one of the main complications of open fractures. Broad-spectrum antibiotics have been used for prophylaxis and treatment of infection in these fractures. The duration of antibiotic prophylaxis remains controversial, especially for the different types and grades of open fractures. No complete review, to date, has been performed of published studies to demonstrate the wide variety of duration of antibiotic use in practice to prevent infection, especially in open tibial fractures. The purpose of the present study was to review the evidence in the current data regarding the duration of prophylactic antibiotic administration in open tibial fractures and to identify the optimum duration of administration of antibiotics to minimize the risk of infection in these fractures. We reviewed and evaluated all published clinical trials claiming or cited elsewhere as being authoritative regarding the duration of prophylactic antibiotic use in open tibial fracture management. A large number of studies reported antibiotic prophylaxis in open fractures; however, only 8 met the inclusion criteria set out for our review. Only 1 randomized, double-blind, prospective study examined the duration of prophylactic antibiotic administration in open tibial fractures. That study suggested a short course of antibiotics is as effective as a long course in infection prophylaxis. The results of the present review highlight the need for a rigorous randomized, double-blind, multicenter trial to establish an agreed protocol for the optimal length of prophylactic antibiotic administration in open tibial fractures. PMID- 26364702 TI - Endosseous Fixation Device for Lapidus Arthrodesis: Technique, Early Experience, and Comparison With Crossed Screw Fixation. AB - First metatarsal cuneiform joint arthrodesis has been commonly used since the early 1900s for definitive treatment of a variety of conditions involving the medial column of the foot. Early applications of this procedure resulted in a relatively high rate of complications, including malunion and nonunion. We retrospectively examined a novel method of fixation involving an endosseous implant with a nonporous, rough exterior surface and compared it with the traditional crossed screw fixation, considered the standard of care for the procedure. Twenty-one feet in 19 patients served as the control group with crossed screws, and 18 feet in 17 patients served as the trial group using the study device. Null hypothesis testing was used to compare the outcomes parameters between the comparative groups. Postoperatively, the patients were allowed to walk in a prefabricated, removable, below-the-knee cast boot at a mean of 48.3 +/ 8.2 days in the control group and 24.4 +/- 9.7 days in the trial group. These differences were highly significant (p < .0001). Postoperatively, the patients were allowed to walk in a stiff-soled shoe at a mean of 65.2 +/- 8.4 days in the control group and 49.7 +/- 19.2 days in the trial group. These differences were also statistically significant (p = .0020). The patients in the control group required revision surgery in 7 of 21 procedures (33%), with 2 patients developing nonunion (9.5%). Only 1 patient in the trial group required revision surgery (5.8%), and no patient developed nonunion. From these results, we believe that the endosseous trial implant is a reliable option for fixation of the first metatarsal cuneiform arthrodesis procedure and might allow for earlier weightbearing with fewer postoperative complications. PMID- 26364703 TI - The Relationship Between the Sesamoid Complex and the First Metatarsal After Hallux Valgus Surgery Without Lateral Soft-Tissue Release: A Prospective Study. AB - Some investigators have emphasized restoring the relationship between the sesamoid complex and the first metatarsal head to reduce the risk of hallux valgus recurring after surgical reconstruction. In a prospective study, we analyzed whether the first metatarsophalangeal joint could be realigned after scarf-Akin bunionectomy without lateral soft tissue release. A total of 25 feet, in 22 patients, were prospectively enrolled and analyzed using anteroposterior radiographs and coronal computed tomography scans obtained before and 3 months after surgery. The Yildirim sesamoid position decreased from a preoperative of 2 (range 1 to 3) to a postoperative position of 0 (range 0 to 1; p < .001), the mean first intermetatarsal angle decreased from 12.6 degrees +/- 2.4 degrees to 5.8 degrees +/- 2.1 degrees (p < .001), and the mean distance between the second metatarsal and the tibial sesamoid changed from 25.7 +/- 4.6 to 25.9 +/- 4.6 (p = .59). Our findings suggest that dislocation of the sesamoid complex is actually caused by displacement of the first metatarsal. In conclusion, the scarf Akin bunionectomy adequately restores the alignment of the first metatarsophalangeal joint, including restoration of the sesamoid apparatus, without direct plantar-lateral soft tissue release. PMID- 26364704 TI - Effect of different amino acid patterns on semen quality of boars fed with low protein diets. AB - The objective of the present study was to determine the effect of different amino acid patterns on the semen quality of boars fed with low-protein diets. Twenty four boars were randomly divided into 4 groups (HP, LP1, LP2, and LP3). HP boars received 17% crude protein diet with a lysine:threonine:tryptophan:arginine (Lys:Thr:Trp:Arg) ratio of 100:50:20:104. Other boars received 13% CP and similar Lys levels (0.84%) with Lys:Thr:Trp:Arg ratios of 100:50:20:71, 100:76:38:71, and 100:76:38:120 for LP1, LP2, and LP3, respectively. These results showed sperm motility in the LP3 group was higher than in HP group during the 13-22 week period. The total sperm number, acrosome integrity ratio, and the effective total sperm number in LP3 and LP2 was higher than in other groups, and the abnormality ratio was lower than in other groups during the 13-18 week period. During 19-22 week period, in LP1 and LP3 groups, total sperm number and effective total sperm number were higher than in other groups, abnormality ratio was lower, and acrosome integrity ratio was higher than in the HP group. Nitric oxide synthase activity of seminal plasma and nitric oxide concentration of spermatozoa were significantly higher in the LP3 group than in other groups. Furthermore, mRNA expression of androgen receptor in testes was up-regulated in LP3. In conclusion, we suggest that the optimum ratio of Lys:Thr:Trp:Arg in a 13% CP diet for boars is 100:76:38:120, which results in similar or better reproductive performances than a 17% CP diet. PMID- 26364705 TI - Optimization of the sperm:oocyte ratio and sperm economy in the artificial reproduction of Rhamdia quelen using fructose as a sperm motility modulator. AB - This research was conducted to evaluate the effects of fructose as a modulator of sperm motility and its effects on the reduction in number of sperm cells in IVF using cryopreserved Rhamdia quelen semen. Sperm activation occurred in solutions containing fructose (0.0, 0.9, 1.8, 2.7, 3.6 and 4.5%). The sperm motility rate, velocity and duration of sperm motility were assessed by polynomial regression analysis and grouped by the principal component analysis (PCA). Then, the oocytes were mixed with semen at proportions of 1*10(4), 3*10(4), 5*10(4), 7*10(4) and 9*10(4) for the sperm:oocyte ratio and fertilization was induced by the activation of gametes with the fructose-containing solutions. The fertilization, hatching and larval normality rate were evaluated by response surface protocol and were further grouped by PCA. All sperm variables were affected by the activating solutions, and the most desirable theoretical results for the rate of sperm motility were obtained when using a solution containing 2.85% fructose. In the IVF and incubation assays, there was an interactive effect between the motile sperm:oocyte ratio and the fructose concentration on the rates of oocyte fertilization, hatching and on the clustered index for reproductive success. The results suggest the possibility of reducing the sperm cells on IVF by 17.77% when using a solution containing 2.28% fructose. In conclusion, the use of solutions containing fructose at concentrations that maximize sperm movement allow the reduction of the motile sperm:oocyte ratio, thus promoting sperm metabolic efficiencies and contributing to the feasibility of using cryopreserved semen at a large-scale in IVF. PMID- 26364706 TI - Benefits and problems of health-care robots in aged care settings: A comparison trial. AB - AIM: This study investigated whether multiple health-care robots could have any benefits or cause any problems in an aged care facility. METHOD: Fifty-three residents and 53 staff participated in a non-randomised controlled trial over 12 weeks. Six robots provided entertainment, communication and health-monitoring functions in staff rooms and activity lounges. These settings were compared to control settings without robots. RESULTS: There were no significant differences between groups in resident or staff outcomes, except a significant increase in job satisfaction in the control group only. The intervention group perceived the robots had more agency and experience than the control group did. Perceived agency of the robots decreased over time in both groups. Overall, we received very mixed responses with positive, neutral and negative comments. CONCLUSIONS: The robots had no major benefits or problems. Future research could give robots stronger operational roles, use more specific outcome measures, and perform cost benefit analyses. PMID- 26364708 TI - Ammine Calcium and Strontium Borohydrides: Syntheses, Structures, and Properties. AB - A new series of solvent- and halide-free ammine strontium metal borohydrides Sr(NH3 )n (BH4 )2 (n=1, 2, and 4) and further investigations of Ca(NH3 )n (BH4 )2 (n=1, 2, 4, and 6) are presented. Crystal structures have been determined by powder XRD and optimized by DFT calculations to evaluate the strength of the dihydrogen bonds. Sr(NH3 )(BH4 )2 (Pbcn) and Sr(NH3 )2 (BH4 )2 (Pnc2) are layered structures, whereas M(NH3 )4 (BH4 )2 (M=Ca and Sr; P21 /c) are molecular structures connected by dihydrogen bonds. Both series of compounds release NH3 gas upon thermal treatment if the partial pressure of ammonia is low. Therefore, the strength of the dihydrogen bonds, the structure of the compounds, and the NH3 /BH4 (-) ratio for M(NH3 )n (BH4 )m have little influence on the composition of the released gasses. The composition of the released gas depends mainly on the thermal stability of the ammine metal borohydride and the corresponding metal borohydride. PMID- 26364709 TI - Nanoparticle agglomerates of indomethacin: The role of poloxamers and matrix former on their dissolution and aerosolisation efficiency. AB - Nanoparticles (NPs) were prepared and assembled to microsized agglomerates with and without matrix formers (mannitol and L-leucine) by coupling wet milling and spray drying to harmonise the advantages of NPs with handling and aerodynamics of microparticles without induction of amorphisation. Indomethacin was selected as poorly water-soluble drug and poloxamers with different ratios of hydrophilic to hydrophobic domains were evaluated as stabilisers comparatively to D-alpha Tocopherol polyethylene-glycol succinate (TPGS). Particle size of nanosuspensions and morphology, size, crystal form, drug loading, redispersibility, in vitro dissolution, and in vitro aerosolisation of NP-agglomerates were determined. Molecular weight of stabilisers affected the rate but not the limit of NP size reduction and the length of hydrophilic segment in poloxamers was found important for the nanosuspension stabilisation. SEM revealed the structure of agglomerates consisting of nanocrystal assemblies. XRPD with DSC proved that NP agglomerates retained their crystallinity. NP-agglomerates exhibited enhanced dissolution compared to physical mixtures of drug and stabilisers while incorporation of matrix formers enabled redispersibility upon hydration and further increased the drug dissolution. Also, matrix formers resulted in significantly improved aerosolisation with higher fine particle fractions (49-62%) and smaller mass median aerodynamic diameters (<3.5 MUm), compared to cases without matrix formers (34-43% and <4.5 MUm). PMID- 26364710 TI - Development of self emulsifying lipid formulations of BCS class II drugs with low to medium lipophilicity. AB - Lipid-based formulations can be effective drug delivery systems for poorly water soluble chemical entities, provided they are designed with careful selection of the excipients, based on their role in the delivery system and in relation to drug properties. The primary factor leading to increased bioavailability is the administration of the drug in a pre-dissolved state thereby avoiding the dissolution limiting step. All model drugs tested (piroxicam, curcumin and nifedipine) belong to the same chemical space--small BCS class II molecules with logP ranging from 2 to 3. These drugs, exhibiting low to medium logP, are not soluble in lipophilic lipid-based excipients (e.g., vegetable oils). Water soluble and water-dispersible surfactants are able to dissolve the target dose of each drug in the dosage form and efficiently keep it in solution during dispersion. In vitro digestion testing was necessary to discriminate formulations and enable selection of the most robust one. For each molecule, the system with the best performance during dispersion/digestion tests did not comprise the surfactant which delivered the highest solvent capacity for the drug. This study demonstrates the potential of surfactant-based formulations - i.e., Type IV systems from the lipid formulation classification system - for this type of hydrophobic drug. PMID- 26364707 TI - On the predictive utility of animal models of osteoarthritis. AB - Animal models of osteoarthritis are extensively used for investigating disease pathways and for preclinical testing of novel therapies. Their predictive utility, however, has often been questioned, mainly because preclinical efficacy of novel therapeutics is poorly translated in clinical trials. In the current narrative review, we consider the preclinical models that were used to support undertaking clinical trials for disease-modifying osteoarthritis drugs, and compare outcomes between clinical and preclinical studies. We discuss this in light of the 1999 Food and Drug Administration draft guidelines for industry for use in the development of drugs, devices, and biological products intended for the treatment of osteoarthritis, which raised five considerations on the usefulness of osteoarthritis models. We systematically discuss what has been learnt regarding these five points since 1999, with emphasis on replicating distinct risk factors and subtypes of human osteoarthritis, and on comprehensive evaluation of the disease in animals, including pathology of all joint tissues, biomarker analysis, and assessment of pain and joint function. Finally, we discuss lessons learnt and propose some recommendations for how the evidence from preclinical research might be strengthened with a view to improving success in clinical translation. PMID- 26364711 TI - Role of solid carriers in pharmaceutical performance of solid supersaturable SEDDS of celecoxib. AB - Self emulsifying drug delivery system (SEDDS) has been increasingly used for improving the oral bioavailability of poorly water soluble drugs. SEDDS can be solidified by adsorbing them on different solid carriers. In the present study, the impact of properties of solid carrier on drug release profile from solid SEDDS was investigated. Celecoxib (CEL) loaded supersaturable SEDDS (S-SEDDS) was prepared and optimized by using optimal response surface design. Optimum composition of S-SEDDS corresponded to 10:45:45% v/v ratio of oil (Capryol 90), surfactant (Tween 20) and cosurfactant (Transcutol HP) with Soluplus (40 mg) as precipitation inhibitor. Different grades of silicon dioxide were selected based on their properties like surface area, porosity and hydrophobicity hydrophilicity, and used for preparation of solid S-SEDDS (SS-SEDDS) by adsorption method. All SS-SEDDS formulations in release studies, gave droplet size, PDI and zeta potential similar to S-SEDDS. The percent drug release after 120min from CEL powder, S-SEDDS and SS-SEDDS with Sylysia 350 fcp, Aerosil 300 Pharma, Aerosil 200 Pharma and Aerosil R 972 Pharma was found to be 0.58%, 100%, 38.44%, 9.63%, 2.53% and 5.99%, respectively. Drug release profiles were compared by using model independent methods. The differential drug release behavior of SS SEDDS was attributed to the different physico-chemical properties of solid carriers. SS-SEDDS with Sylysia 350 fcp showed higher drug release and greater dissolution efficiency. Oral bioavailability study also demonstrated 2.34 fold increase in Cmax and 4.82 fold increase in AUC (0-24h) when compared with CEL powder. This study highlights the rational for selection of solid carriers in the formulation development of solid SEDDS. PMID- 26364712 TI - Self-assembled nanostructured aqueous dispersions as dermal delivery systems. AB - Due to their high interfacial area and capability of loading hydrophobic, hydrophilic and amphiphilic drugs, self-assembled nanoparticles are the subject of much attention in view of an application of these dispersions as carrier systems for a variety of different active ingredients. Therefore, the effect of the internal nanostructure of oil-loaded monoglyceride-based nanoparticles on the dermal delivery of diclofenac sodium was investigated. The different self assembled phases of the nanostructured aqueous dispersions were characterized by small angle X-ray scattering (SAXS). The influence of the different phases ranging from cubic-bicontinuous, over hexagonal and cubic-micellar phases to emulsified microemulsions on the dermal delivery of the incorporated active was examined by Franz-type diffusion cell and in vitro tape stripping experiments on porcine skin. These studies revealed a dependency of the skin permeation of diclofenac sodium on the formulation's internal structure, which could be modified by varying the amount of R-(+)-limonene in the oil phase. A superiority of the emulsified microemulsion, possessing the highest amount of R-(+)-limonene, over cubic or hexagonal phases was evidenced in terms of dermal drug delivery. PMID- 26364713 TI - Collective relaxation dynamics and crystallization kinetics of the amorphous Biclotymol antiseptic. AB - We employ dielectric spectroscopy to monitor the relaxation dynamics and crystallization kinetics of the Biclotymol antiseptic in its amorphous phase. The glass transition temperature of the material as determined by dielectric spectroscopy is Tg = 290 +/- 1K. The primary (alpha) relaxation dynamics is observed to follow a Vogel-Fulcher-Tammann temperature dependence, with a kinetic fragility index m = 86 +/- 13, which classifies Biclotymol as a relatively fragile glass former. A secondary relaxation is also observed, corresponding to an intramolecular dynamic process of the non-rigid Biclotymol molecule. The crystallization kinetics, measured at four different temperatures above the glass transition temperature, follows an Avrami behavior with exponent virtually equal to n = 2, indicating one-dimensional crystallization into needle-like crystallites, as experimentally observed, with a time-constant nucleation rate. The activation barrier for crystallization is found to be Ea = 115 +/- 22 kJ mol( 1). PMID- 26364715 TI - Psychosocial Interventions Pre and Post Bariatric Surgery. AB - Despite positive results overall, a substantial number of patients experience poor long-term outcomes following bariatric surgery. One reason for variability in weight loss may be difficulty in making and sustaining changes in dietary intake and physical activity; post-surgery binge eating has also been associated with poorer weight outcomes. In this paper, we review available evidence on adjunctive psychosocial interventions for bariatric surgery patients. Although the literature is limited, evidence suggests that bariatric surgery patients may benefit from a comprehensive approach targeting diet, activity and psychological factors. We think the optimal time to initiate adjunctive intervention is after surgery, but before significant weight regain has occurred. Adaptive interventions incorporating advances in technology may prove to be effective for promoting behavioural self-management and psychosocial adjustment following bariatric surgery. For some patients, pharmacotherapy and reoperation may also play a role in a personalized approach to post-surgery care. PMID- 26364714 TI - Incomplete reporting of enhanced recovery elements and its impact on achieving quality improvement. AB - BACKGROUND: Enhanced recovery (ER) protocols are used widely in surgical practice. As protocols are multidisciplinary with multiple components, it is difficult to compare and contrast reports. The present study examined compliance and transferability to clinical practice among ER publications related to colorectal surgery. METHODS: PubMed, Embase and Cochrane Central Register databases were searched for current colorectal ER manuscripts. Each publication was assessed for the number of ER elements, whether the element was explained sufficiently so that it could be transferred to clinical practice, and compliance with the ER element. RESULTS: Some 50 publications met the reporting criteria for inclusion. A total of 22 ER elements were described. The median number of elements included in each publication was 9, and the median number of included patients was 130. The elements most commonly included in ER pathways were early postoperative diet advancement (49, 98 per cent) and early mobilization (47, 94 per cent). Early diet advancement was sufficiently explained in 43 (86 per cent) of the 50 publications, but only 22 (45 per cent) of 49 listing the variable reported compliance. The explanation for early mobilization was satisfactory in 41 (82 per cent) of the 50 publications, although only 14 (30 per cent) of 47 listing the variable reported compliance. Other ER elements had similar rates of explanation and compliance. The most frequently analysed outcome measures were morbidity (49, 98 per cent), length of stay (47, 94 per cent) and mortality (45, 90 per cent). CONCLUSION: The current standard of reporting is frequently incomplete. To transfer knowledge and facilitate implementation of pathways that demonstrate improvements in perioperative care and recovery, a consistent structured reporting platform is needed. PMID- 26364716 TI - Hydrolyzed whey protein prevents the development of food allergy to beta lactoglobulin in sensitized mice. AB - Food allergy is an adverse immune response to dietary proteins. Hydrolysates are frequently used for children with milk allergy. However, hydrolysates effects afterwards are poorly studied. The aim of this study was to investigate the immunological consequences of hydrolyzed whey protein in allergic mice. For that, we developed a novel model of food allergy in BALB/c mice sensitized with alum adsorbed beta-lactoglobulin. These mice were orally challenged with either whey protein or whey hydrolysate. Whey-challenged mice had elevated levels of specific IgE and lost weight. They also presented gut inflammation, enhanced levels of SIgA and IL-5 as well as decreased production of IL-4 and IL-10 in the intestinal mucosa. Conversely, mice challenged with hydrolyzate maintained normal levels of IgE, IL-4 and IL-5 and showed no sign of gut inflammation probably due to increased IL-12 production in the gut. Thus, consumption of hydrolysate prevented the development of clinical signs of food allergy in mice. PMID- 26364717 TI - Calorimetric study on pH-responsive block copolymer grafted lipid bilayers: rational design and development of liposomes. AB - This study is focused on chimeric advanced drug delivery nanosystems and specifically on pH-sensitive liposomes, combining lipids and pH-responsive amphiphilic block copolymers. Chimeric liposomes composed of 1,2-dipalmitoyl-sn glycero-3-phosphocholine (DPPC) and two different forms of block copolymers, i.e. poly(n-butylacrylate)-b-poly(acrylic acid) (PnBA-b-PAA) at 70 and 85% content of PAA at six different molar ratios, each form respectively. PAA block exhibits pH responsiveness, because of the regulative group of -COOH. -COOH is protonated under acidic pH (pKa ca. 4.2), while remains ionized under basic or neutral pH, leading to liposomes repulse and eventually stability. Lipid bilayers were prepared composed of DPPC and PnBA-b-PAA. Experiments were carried out using differential scanning calorimetry (DSC) in order to investigate their thermotropic properties. DSC indicated disappearance of pre-transition at all chimeric lipid bilayers and slight thermotropic changes of the main transition temperature. Chimeric liposomes have been prepared and their physicochemical characteristics have been explored by measuring the size, size distribution and zeta-potential, owned to the presence of pH-responsive polymer. At percentages containing medium to high amounts of the polymer, chimeric liposomes were found to retain their size during the stability studies. These results were well correlated with those indicated in the DSC measurements of lipid bilayers incorporating polymers in order to explain their physicochemical behavior. The incorporation of the appropriate amount of these novel pH-responsive block copolymers affects thus the cooperativity, the liposomal stabilization and imparts pH-responsiveness. PMID- 26364718 TI - Factors influencing the spatial distribution of Anopheles larvae in Coimbatore District, Tamil Nadu, India. AB - Malaria causes extensive morbidity and mortality in humans and results in significant economic losses in India. The distribution of immature malaria transmitting Anopheles mosquitoes was studied in 17 villages in Coimbatore District as a prelude to the development and implementation of vector control strategies that are intended to reduce the risk of human exposure to potentially infectious mosquitoes. Eight Anopheles species were recorded. The most numerous species were Anopheles vagus, Anopheles subpictus, and Anopheles hyrcanus. The location of mosquito development sites and the density of larvae in each village was evaluated for correlation with selected demographic, biologic, and land use parameters using remote sensing and geographic information systems (GIS) technology. We found the number of mosquito development sites in a village and the density of larvae in such sites to be positively correlated with human population density but not the surface area (km(2)) of the village. The number of mosquito development sites and the density of larvae in each site were not correlated. Data from this study are being used to construct a GIS-based mapping system that will enable the location of aquatic habitats with Anopheles larvae in the Coimbatore District, Tamil Nadu, India as target sites for the application of vector control. PMID- 26364719 TI - Novel detection of Helicobacter pylori in fish: A possible public health concern. AB - Helicobacter pylori is one of the most common human pathogens worldwide with serious clinical outcomes. Although, H. pylori is a major water-borne pathogen, its occurrence in fish is still unknown. This leads us to conduct the current study in order to clarify this point and to investigate the potential role of fish in the epidemiology of H. pylori. For this purpose, fecal samples were obtained from 315 fish from different species and were caught from various aquatic environments at different localities in Egypt. The obtained fecal samples were examined for the occurrence of H. pylori using monoclonal antibody based lateral flow immunoassay for antigen detection and after then the positive samples were confirmed by PCR. In addition, fecal samples from 18 fish handlers were also examined for the presence of H. pylori by lateral flow technique. The overall prevalence rates of H. pylori in the examined fish were 6.7% and 1.9% for LF and PCR, respectively, whereas 61.1% of fish handlers were positive. Only tilapia fish showed positive results by both techniques in rates 10.9% and 3.1%, respectively. Interestingly, H. pylori was detected in cultured and wild tilapia in various aquatic environments at different localities, whereas all other fish species were negative even those that were collected from the same water source where positive tilapia were caught. These results concluded that tilapia fish may be considered as a potential zoonotic reservoir for H. pylori and thus, H. pylori may become a new fish-borne pathogen. Further studies are needed to investigate the occurrence of H. pylori in other fish species. PMID- 26364720 TI - The lncRNA MALAT1 protects the endothelium against ox-LDL-induced dysfunction via upregulating the expression of the miR-22-3p target genes CXCR2 and AKT. AB - CXCR2 plays a key role in protecting the integrity of the endothelium. Emerging evidence has demonstrated that the long ncRNAs (lncRNA) Human metastasis associated lung adenocarcinoma transcript 1 (MALAT1) participates in the regulation of the pathophysiological processes. However, whether there is crosstalk between CXCR2 and MALAT1 remains unknown. In this study, we demonstrated that MALAT1 was upregulated in patients with unstable angina. MALAT1 silencing significantly downregulated the expression of the miR-22-3p target gene CXCR2 via reversing the effect of the miR-22-3p, resulting in the aggravation of Oxidized low-density lipoprotein (ox-LDL)-induced endothelial injury; this process was associated with the AKT pathway. Thus, MALAT1 protects the endothelium from ox-LDL-induced endothelial dysfunction partly through competing with miR-22-3p for endogenous RNA. PMID- 26364721 TI - Primary processing of CRISPR RNA by the endonuclease Cas6 in Staphylococcus epidermidis. AB - In many bacteria and archaea, an adaptive immune system (CRISPR-Cas) provides immunity against foreign genetic elements. This system uses CRISPR RNAs (crRNAs) derived from the CRISPR array, along with CRISPR-associated (Cas) proteins, to target foreign nucleic acids. In most CRISPR systems, endonucleolytic processing of crRNA precursors (pre-crRNAs) is essential for the pathway. Here we study the Cas6 endonuclease responsible for crRNA processing in the Type III-A CRISPR-Cas system from Staphylococcus epidermidis RP62a, a model for Type III-A CRISPR-Cas systems, and define substrate requirements for SeCas6 activity. We find that SeCas6 is necessary and sufficient for full-length crRNA biogenesis in vitro, and that it relies on both sequence and stem-loop structure in the 3' half of the CRISPR repeat for recognition and processing. PMID- 26364722 TI - Flocculation in Saccharomyces cerevisiae is regulated by RNA/DNA helicase Sen1p. AB - The Nrd1-Nab3-Sen1 (NNS) complex terminates transcription of non-coding RNA genes and mediates degradation of the produced transcript by the nuclear exosome. The NNS complex also represses some stress response genes, by stimulating premature termination. A well-characterized stress response in yeast is flocculation, where cells aggregate to form flocs under expression of lectin-encoding genes designated as FLOs. In this study, we demonstrated the role of the NNS complex and Rrp6p in the expression of flocculation genes: FLO1, FLO5, FLO9, and FLO10. Furthermore, a deletion mutant of the RNA processing machinery (RNT1), and SEN1 mutants that are unable to interact with Rnt1p, exhibit a flocculation phenotype. In summary, we have identified a cooperative role of Rnt1p, Rrp6p and the NNS complex in the repression of FLO genes. PMID- 26364724 TI - The feasibility of using 5D CNS software in obtaining standard fetal head measurements from volumes acquired by three-dimensional ultrasonography: comparison with two-dimensional ultrasound. AB - OBJECTIVE: To evaluate the performance of a new software (5D CNS) developed to automatically recognize the axial planes of the fetal brain from three dimensional volumes and to obtain the basic standard biometric measurements. The accuracy, reproducibility, and time required for analysis of 5D CNS were compared with that of two-dimensional (2D) ultrasound. METHODS: This was a prospective study of 120 uncomplicated singleton pregnancies undergoing routine second trimester examination. For every pregnancy standard biometric measurements including biparietal diameter, head circumference, distal lateral ventricle width, transverse cerebellar diameter and cisterna magna width were obtained using 2D ultrasound and three-dimensional (3D) ultrasound with 5D CNS software. Reliability and agreement of the two techniques were evaluated using intraclass correlation coefficients (ICCs) and proportionate Bland-Altman plots were constructed. The time necessary to complete the measurements with either technique was compared and intraobserver and interobserver agreements of measurements calculated. RESULTS: In 118/120 (98.3%), 5D CNS successfully reconstructed the axial diagnostic planes and calculated all the basic biometric head and brain measurements. The agreement between the two techniques was high for all the measurements considered (all ICCS > 0.920). The time necessary to measure the biometric variables considered was significantly shorter with 5D CNS (54 versus 115 s, p < 0.0001) than with 2D ultrasonography. No significant differences were found in 5D CNS repeated measurements obtained either by the same observer or by two independent observers. CONCLUSION: 5D CNS software allows us to obtain reliable biometric measurements of the fetal brain and to reduce the examination time. Its application may improve work-flow efficiency in ultrasonographic practices. PMID- 26364723 TI - Modeling chromosomes: Beyond pretty pictures. AB - Recently, Chromosome Conformation Capture (3C) based experiments have highlighted the importance of computational models for the study of chromosome organization. In this review, we propose that current computational models can be grouped into roughly four classes, with two classes of data-driven models: consensus structures and data-driven ensembles, and two classes of de novo models: structural ensembles and mechanistic ensembles. Finally, we highlight specific questions mechanistic ensembles can address. PMID- 26364725 TI - Female sex hormones modulate Porphyromonas gingivalis lipopolysaccharide-induced Toll-like receptor signaling in primary human monocytes. AB - BACKGROUND AND OBJECTIVE: Female sex hormones are elevated and are potential host response modifiers during pregnancy. Modulation of immune responses by estrogen and progesterone may be responsible for periodontal inflammation. Therefore, we aimed to investigate the role of beta-estradiol and progesterone in human monocyte immune responses, at cellular and molecular levels, to identify their role as a possible immunological link between pregnancy and periodontal disease. MATERIAL AND METHODS: Primary human monocytes were purified from human peripheral blood mononuclear cells by adherent method. Expression of Toll-like receptor (TLR) 2, 4 and CD14 was analyzed by flow cytometry. TLR2, TLR4, cyclooxygenase-2 (COX2), nuclear factor-kappa B (NF-kappaB) and NF-kappaB inhibitor-alpha mRNA expressions were measured using real-time reverse transcriptase-polymerase chain reaction and prostaglandin E2 secretion was assayed by enzyme-linked immunosorbent assay. NF-kappaB expression was also examined by immunofluorescence. Western blotting was performed to determine the activation of mitogen-activated protein kinase pathway. RESULTS: We report herein that both beta-estradiol and progesterone significantly reduced TLR2 expression at both protein and mRNA levels but had less of an effect on TLR4 expression in primary human monocytes. We also found that the hormones decreased monocyte cell surface protein expression of CD14. Significantly, beta-estradiol and progesterone dose dependently downregulated monocyte expression of COX2 mRNA. Pretreatment monocytes with beta-estradiol or progesterone reduced effects of Porphyromonas gingivalis lipopolysaccharide (LPS) on COX2 mRNA expression and decreased prostaglandin E2 secretion by the monocytes. Furthermore, we demonstrated that both beta-estradiol and progesterone inhibited P. gingivalis LPS-induced NF kappaB signaling pathway through the upregulation of NF-kappaB inhibitor-alpha expression. However, neither beta-estradiol nor progesterone altered the phosphorylation of the p38, the extracellular signal-regulated kinase 1/2 and the c-Jun N-terminal activated kinase in P. gingivalis LPS-stimulated monocytes. Thus, the inhibitory effects of these hormones on the response of human monocytes to P. gingivalis LPS appear to be independent on mitogen-activated protein kinase signaling pathway. CONCLUSION: The results of the present study suggest that beta estradiol and progesterone could influence the immune response of human monocytes to periodontal pathogens and this process may have a role in the clinical manifestations of periodontal disease associated with pregnancy. PMID- 26364726 TI - Prognostic significance of PLA2G4C gene polymorphism in patients with stage II colorectal cancer. AB - BACKGROUND: Phospholipase A2 Group IV C (PLA2G4C) catalyzes the release of certain fatty acids from phospholipids and plays a role in a range of physiological functions, such as remodeling of cell membranes and the production of prostaglandins. Furthermore, it has been proposed that PLA2G4C plays an important role in breast cancer cell chemotaxis. This study aimed to investigate the effect of a single nucleotide polymorphism (SNP) rs1549637 (T>A) of the PLA2G4C gene on the prognosis of colorectal cancer (CRC). MATERIAL AND METHODS: Whole blood DNA was extracted from 381 patients with CRC and 618 controls, and a TaqMan SNP genotyping assay was used to determine the distribution of the genotypes. Cancer-specific and disease-free survival was analyzed by Kaplan-Meier graphs and by uni- and multivariable Cox regression. RESULTS: The cancer-specific survival differed between the genotypes (p = 0.019) and the carriers of the A allele were associated with the highest risk of CRC death, with a hazard ratio (HR) of 1.72 [95% confidence interval (CI) 1.17-2.53, p = 0.006] compared with homozygous carriers of the T allele. This increased mortality in the carriers with the allele A was especially marked in stage II with an HR of 3.84 (95% CI 1.51-9.78, p = 0.005). CONCLUSION: The A allele in PLA2G4C SNP (rs1549637) is associated with a worse prognosis in patients with CRC, especially in stage II disease, and it could be a potential prognostic biomarker in the planning of individual adjuvant therapy in stage II patients. PMID- 26364727 TI - Nanostructured SnS-N-doped graphene as an advanced electrocatalyst for the hydrogen evolution reaction. AB - The hydrogen evolution reaction (HER) via water splitting requires the development of advanced and inexpensive electrocatalysts to replace expensive platinum (Pt)-based catalysts. The scalable hydrothermal synthesis of SnS on N reduced graphene (N-rGr) sheets is presented for the first time, which is used as a highly-active electrocatalyst with long-term stability in acidic, neutral, and alkaline media. This hybrid catalyst reveals a low overpotential of -125 mV, Tafel slope of 38 mV dec(-1), exchange current density of 6.23 mA cm(-2), onset potential of 59 mV, and long-term durability. PMID- 26364728 TI - A Retrospective Comparison of Mycophenolate Mofetil with Low-Exposure Cyclosporine Versus Standard Cyclosporine Therapy in De Novo Liver Transplant Patients. AB - BACKGROUND Data on low-exposure calcineurin inhibitor therapy with mycophenolate mofetil (MMF) in de novo liver transplant patients are limited and restricted to tacrolimus. MATERIAL AND METHODS Twenty-eight patients receiving cyclosporine and MMF at a single center were identified retrospectively and categorized as low exposure or standard-exposure CsA (median concentration <80 ng/mL [n=16] or >=80 ng/mL [n=12] during days 1-7) and analyzed to 12 weeks post-transplant. RESULTS Biopsy-proven acute rejection (Banff >=4) occurred in 3 low-CsA patients and no standard-CsA patients (p=0.238); graft failure occurred in 4 and zero patients, respectively (p=0.113); no graft loss was attributable to rejection. Mean (SD) estimated GFR at baseline and week 12 was 79.5 (45.3) and 79.3 (24.5) mL/min/1.73 m2 in the low-CsA group (p=0.508), and 106.0 (66.9) and 86.7 (23.2) mL/min/1.73 m2 in the standard-CsA group (p=0.093). Estimated GFR decreased significantly in patients with good baseline renal function (>=80 mL/min/1.73 m2) in the standard CsA (p=0.028) and increased markedly in patients with poor function (<=60 mL/min/1.73 m2) given low-CsA (p=0.043). There was no significant between-group difference regarding incidence of infections. CONCLUSIONS These preliminary findings suggest that immunosuppressive efficacy is maintained with low-exposure CsA and MMF in de novo liver transplant patients and good baseline renal function may be better preserved, but no benefit for infections was observed. PMID- 26364729 TI - In vitro activity of aminoglycosides against clinical isolates of Acinetobacter baumannii complex and other nonfermentative Gram-negative bacilli causing healthcare-associated bloodstream infections in Taiwan. AB - BACKGROUND/PURPOSE: Aminoglycosides possess in vitro activity against aerobic and facultative Gram-negative bacilli. However, nationwide surveillance on susceptibility data of Acinetobacter baumannii complex and Pseudomonas aeruginosa to aminoglycosides was limited, and aminoglycoside resistance has emerged in the past decade. We study the in vitro susceptibility of A. baumannii complex and other nonfermentative Gram-negative bacilli (NFGNB) to aminoglycosides. METHODS: A total of 378 NFGNB blood isolates causing healthcare-associated bloodstream infections during 2008 and 2013 at four medical centers in Taiwan were tested for their susceptibilities to four aminoglycosides using the agar dilution method (gentamicin, amikacin, tobramycin, and isepamicin) and disc diffusion method (isepamicin). RESULTS: A. baumannii was highly resistant to all four aminoglycosides (range of susceptibility, 0-4%), whereas >80% of Acinetobacter nosocomialis and Acinetobacter pittii blood isolates were susceptible to amikacin (susceptibility: 96% and 91%, respectively), tobramycin (susceptibility: 92% and 80%, respectively), and isepamicin (susceptibility: 96% and 80%, respectively). All aminoglycosides except gentamicin possessed good in vitro activity (>94%) against P. aeruginosa. Amikacin has the best in vitro activity against P. aeruginosa (susceptibility, 98%), followed by A. nosocomialis (96%), and A. pittii (91%), whereas tobramycin and isepamicin were less potent against A. pittii (both 80%). Aminoglycoside resistances were prevalent in Stenotrophomonas maltophilia and Burkholderia cepacia complex blood isolates in Taiwan. CONCLUSION: Genospecies among the A. baumannii complex had heterogeneous susceptibility profiles to aminoglycosides. Aminoglycosides, except gentamicin, remained good in vitro antimicrobial activity against P. aeruginosa. Further in vivo clinical data and continuous resistance monitoring are warranted for clinical practice guidance. PMID- 26364730 TI - Antipsychotic treatment reduces psychotic symptoms and markers of low-grade inflammation in first episode psychosis patients, but increases their body mass index. AB - OBJECTIVE: The main goal of the present study was to analyze levels of cytokines of the interleukin family (IL-1alpha, IL-1beta, IL-2, IL-4, IL-6, IL-8 and IL 10), interferon-gamma (IFN-gamma), monocyte chemoattractant protein-1 (MCP1), tumor necrosis factor-alpha (TNF-alpha), and vascular endothelial and endothelial growth factors (VEGF and EGF), in the blood samples of first-episode psychosis (FEP) patients before and seven months after the start of antipsychotic medication use. METHOD: 38 anti-psychotic medication-naive FEP patients and 37 healthy controls (HC) were recruited. Biochip array technology was used to measure cytokines and growth factors. RESULTS: The comparison of these markers in FEP patients and HC revealed significantly higher levels of EGF, IL-4 and IL-6 and significantly lower level of IL-1beta in FEP patients before the antipsychotic treatment. Multiple regression analysis demonstrated significant correlations between FEP and EGF, IL-1beta and smoking. Treatment with antipsychotic drugs resulted in a statistically significant amelioration of the symptoms of psychosis, but caused a significant increase in the body mass index (BMI) of patients. Levels of EGF, IL-2, VEGF, IL-6, IFN-gamma, IL-4, IL-8 and IL 1alpha were significantly lower in treated FEP patients compared to premedication levels. CONCLUSIONS: According to the present study, EGF and IL-1beta are markers of FEP. Antipsychotic drug treatment resulted in a significant clinical improvement of FEP patients and the suppression of positive symptoms was correlated with the decreased levels of EGF, IL-2 and IL-4. EGF was the strongest marker of FEP and treatment efficiency among the measured cytokines and growth factors. PMID- 26364731 TI - Spirometric prediction equations and the relationship between metabolic syndrome and spirometric parameters from an island in Fujian, China. AB - BACKGROUND: We investigated risk factors for decreased lung function among Chinese island residents (>=30 years) to determine the relationship between metabolic syndrome (MS) and decreased lung function. METHODS: From October 17, 2011 to November 1, 2011, 2607 residents aged >=30 years who lived on the Huangqi Peninsula of Fujian were enlisted by random cluster sampling. They completed a questionnaire designed according to the Burden of Obstructive Lung Disease (BOLD) questionnaire, and underwent physical examination, blood test, and lung function evaluation. We constructed spirometric prediction equations for forced vital capacity (FVC) and forced expiratory volume in one second (FEV1), determined the lower limits of normal for FVC, FEV1 and FEV1/FVC, and examined the relationship between lung function and MS. RESULTS: Prediction equations for normal island residents were as follows: FVC (L) = -0.023 * age (years) + 0.042 * height (cm) + 0.641 * weight (kg) - 3.607 (males); FVC (L) = -0.017 * age (years) + 0.030 * height (cm) + 0.009 * weight (kg) - 1.741 (females); FEV1 (L) = -0.023 * age (years) + 0.040 * height (cm) + 0.010 * weight (kg) - 2.999 (males); FEV1 (L) = 0.017 * age (years) + 0.026 * height (cm) + 0.007 * weight (kg) -1.135 (females). The odds ratio for MS for increased risk of decreased FVC was 4.623 (95%CI =3.626 5.894, P<0.001), and for increased risk of decreased FEV1 was 3.043 (95%CI =2.447 3.785, P<0.001). CONCLUSIONS: MS is a risk factor for decreased lung function in island residents >=30 years old. PMID- 26364732 TI - Prior regular exercise improves clinical outcome and reduces demyelination and axonal injury in experimental autoimmune encephalomyelitis. AB - Although previous studies have shown that forced exercise modulates inflammation and is therapeutic acutely for experimental autoimmune encephalomyelitis (EAE), the long-term benefits have not been evaluated. In this study, we investigated the effects of preconditioning exercise on the clinical and pathological progression of EAE. Female C57BL/6 mice were randomly assigned to either an exercised (Ex) or unexercised (UEx) group and all of them were induced for EAE. Mice in the Ex group had an attenuated clinical score relative to UEx mice throughout the study. At 42 dpi, flow cytometry analysis showed a significant reduction in B cells, CD4(+) T cells, and CD8(+) T cells infiltrating into the spinal cord in the Ex group compared to UEx. Ex mice also had a significant reduction in myelin damage with a corresponding increase in proteolipid protein expression. Finally, Ex mice had a significant reduction in axonal damage. Collectively, our study demonstrates for the first time that a prolonged and forced preconditioning protocol of exercise improves clinical outcome and attenuates pathological hallmarks of EAE at chronic disease. In this study, we show that a program of 6 weeks of preconditioning exercise promoted a significant reduction of cells infiltrating into the spinal cord, a significant reduction in myelin damage and a significant reduction in axonal damage in experimental autoimmune encephalomyelitis (EAE) mice at 42 dpi. Collectively, our study demonstrates for the first time that a preconditioning protocol of exercise improves clinical outcome and attenuates pathological hallmarks of EAE at chronic disease. PMID- 26364733 TI - Resolution and contrast enhancement of subtractive second harmonic generation microscopy with a circularly polarized vortex beam. AB - We extend the subtractive imaging method to label-free second harmonic generation (SHG) microscopy to enhance the spatial resolution and contrast. This method is based on the intensity difference between two images obtained with circularly polarized Gaussian and doughnut-shaped beams, respectively. By characterizing the intensity and polarization distributions of the two focused beams, we verify the feasibility of the subtractive imaging method in polarization dependent SHG microscopy. The resolution and contrast enhancement in different biological samples is demonstrated. This work will open a new avenue for the applications of SHG microscopy in biomedical research. PMID- 26364734 TI - Neuronal erythropoietin overexpression protects mice against age-related hearing loss (presbycusis). AB - So far, typical causes of presbycusis such as degeneration of hair cells and/or primary auditory (spiral ganglion) neurons cannot be treated. Because erythropoietin's (Epo) neuroprotective potential has been shown previously, we determined hearing thresholds of juvenile and aged mice overexpressing Epo in neuronal tissues. Behavioral audiometry revealed in contrast to 5 months of age, that 11-month-old Epo-transgenic mice had up to 35 dB lower hearing thresholds between 1.4 and 32 kHz, and at the highest frequencies (50-80 kHz), thresholds could be obtained in aged Epo-transgenic only but not anymore in old C57BL6 control mice. Click-evoked auditory brainstem response showed similar results. Numbers of spiral ganglion neurons in aged C57BL6 but not Epo-transgenic mice were dramatically reduced mainly in the basal turn, the location of high frequencies. In addition, there was a tendency to better preservation of inner and outer hair cells in Epo-transgenic mice. Hence, Epo's known neuroprotective action effectively suppresses the loss of spiral ganglion cells and probably also hair cells and, thus, development of presbycusis in mice. PMID- 26364735 TI - Quantitative analysis of the capillary network of aged APPswe/PS1dE9 transgenic mice. AB - A combination of immunohistochemical and stereological techniques were used to investigate the capillary network in the cerebral cortex of 18-month-old APPswe/PS1dE9 transgenic (Tg) mice and control littermates. Data regarding total capillary length, segment number, diffusion radius, and pericyte number are presented. The total length was 60 meters and there was a one-to-one relationship between the number of capillary segments and pericytes in both groups. Significant differences were not observed in the Tg and wild-type controls indicating that the Alzheimer's-like amyloidosis produced in this Tg mouse has a minimal affect on the structural integrity of the cerebral capillary network. PMID- 26364737 TI - Sphingosine 1-phosphate induced synthesis of glycocalyx on endothelial cells. AB - Sphingosine 1-phosphate (S1P) protects glycocalyx against shedding, playing important roles in endothelial functions. We previously found that glycocalyx on endothelial cells (ECs) was shed after plasma protein depletion. In the present study, we investigated the role of S1P on the recovery of glycocalyx, and tested whether it is mediated by phosphoinositide 3-kinase (PI3K) pathway. After depletion of plasma protein, ECs were treated with S1P for another 6h. And then, the major components of glycocalyx including syndecan-1 with attached heparan sulfate (HS) and chondroitin sulfate (CS) on endothelial cells were detected using confocal fluorescence microscopy. Role of PI3K in the S1P-induced synthesis of glycocalyx was confirmed by using the PI3K inhibitor (LY294002). Syndecan-1 with attached HS and CS were degraded with duration of plasma protein depletion. S1P induced recovery of syndecan-1 with attached HS and CS. The PI3K inhibitor LY294002 abolished the effect of S1P on recovery of glycocalyx. Thus, S1P induced synthesis of glycocalyx on endothelial cells and it is mediated by PI3K pathway. PMID- 26364736 TI - Silencing of TREM2 exacerbates tau pathology, neurodegenerative changes, and spatial learning deficits in P301S tau transgenic mice. AB - Tau pathology is a pathological hallmark for several neurodegenerative diseases including Alzheimer's disease and frontotemporal dementia. As a novel susceptibility gene for these 2 diseases, triggering receptor expressed on myeloid cells 2 (TREM2) gene encodes an immune receptor that is uniquely expressed by microglia. Recently, a correlation between TREM2 expression and hyperphosphorylated tau has been revealed in the brain of Alzheimer's disease patients, suggesting a potential association between TREM2 and tau pathology. However, the role of TREM2 in tau pathology remains unclear thus far. Herein, using P301S mice, we showed that TREM2 was upregulated in microglia during disease progression. Silencing of brain TREM2 exacerbated tau pathology in P301S mice. This exacerbation might be attributed to neuroinflammation-induced hyperactivation of tau kinases. Additionally, more severe neurodegenerative changes and spatial learning deficits were observed following TREM2 silencing. Our results imply that TREM2 attenuates tau kinase activity through restriction of neuroinflammation, and thus protects against tau pathology. These findings further suggest that TREM2 may represent as a potential therapeutic target for tau-related neurodegenerative diseases. PMID- 26364738 TI - Intrabody-mediated diverting of HP1beta to the cytoplasm induces co-aggregation of H3-H4 histones and lamin-B receptor. AB - Diverting a protein from its intracellular location is a unique property of intrabodies. To interfere with the intracellular traffic of heterochromatin protein 1beta (HP1beta) in living cells, we have generated a cytoplasmic targeted anti-HP1beta intrabody, specifically directed against the C-terminal portion of the molecule. HP1beta is a conserved component of mouse and human constitutive heterochromatin involved in diverse nuclear functions including gene silencing, DNA repair and nuclear membrane assembly. We found that the anti-HP1beta intrabody sequesters HP1beta into cytoplasmic aggregates, inhibiting its traffic to the nucleus. Lamin B receptor (LBR) and a subset of core histones (H3/H4) are also specifically co-sequestered in the cytoplasm of anti-HP1beta intrabody expressing cells. Methylated histone H3 at K9 (Me9H3), a marker of constitutive heterochromatin, is not affected by the anti-HP1beta intrabody expression. Hyper acetylating conditions completely dislodge H3 from HP1beta:LBR containing aggregates. The expression of anti-HP1beta scFv fragments induces apoptosis, associated with an alteration of nuclear morphology. Both these phenotypes are specifically rescued either by overexpression of recombinant full length HP1beta or by HP1beta mutant containing the chromoshadow domain, but not by recombinant LBR protein. The HP1beta-chromodomain mutant, on the other hand, does not rescue the phenotypes, but does compete with LBR for binding to HP1beta. These findings provide new insights into the mode of action of cytoplasmic-targeted intrabodies and the interaction between HP1beta and its binding partners involved in peripheral heterochromatin organisation. PMID- 26364739 TI - Increasing the efficiency of traveling wave ultrasonic motor by modifying the stator geometry. AB - Current traveling wave ultrasonic motor (TWUSM) utilizes comb-teeth structure as deflection amplifier. The position of the stator neutral axis to the stator contact surface is one of the factors that influences the deflection amplifier. Stator deflection directly effects on motor performance. In this study, the modification of the comb-teeth stator design is proposed to see its effect on motor efficiency. The modification is done so that the neutral axis position is further distance from the stator top contact surface. The proposed solution is to remove a selected mass element from the comb-teeth structure. Modeling, simulation and experimental work of the proposed concept is carried out utilizing Shinsei USR60 as the chosen TWUSM. The modeling and analyses are conducted through multi-physic finite element simulation MSC Marc Mentat. The results of the analyses and experimental work reveal that the modified comb-teeth stator increases the position of the neutral axis from the stator top surface. Due to the neutral axis shifting, the results also confirm that the proposed modified motor has higher efficiency compared to the non-modified motor. PMID- 26364740 TI - Comparative study of four interleukin 17 cytokines of tongue sole Cynoglossus semilaevis: Genomic structure, expression pattern, and promoter activity. AB - The interleukin (IL)-17 cytokine family participates in the regulation of many cellular functions. In the present study, we analyzed the genomic structure, expression, and promoter activity of four IL-17 members from the teleost fish tongue sole (Cynoglossus semilaevis), i.e. CsIL-17C CsIL-17D, CsIL-17F, and IL 17F like (IL-17Fl). We found that CsIL-17C, CsIL-17D, CsIL-17F, and CsIL-17Fl share 21.2%-28.6% overall sequence identities among themselves and 31.5%-71.2% overall sequence identities with their counterparts in other teleost. All four CsIL-17 members possess an IL-17 domain and four conserved cysteine residues. Phylogenetic analysis classified the four CsIL-17 members into three clusters. Under normal physiological conditions, the four CsIL-17 expressed in multiple tissues, especially non-immune tissues. Bacterial infection upregulated the expression of all four CsIL-17, while viral infection upregulated the expression of CsIL-17D and CsIL-17Fl but downregulated the expression of CsIL-17C and CsIL 17F. The 1.2 kb 5'-flanking regions of the four CsIL-17 exhibited apparent promoter activity and contain a number of putative transcription factor-binding sites. Furthermore, the promoter activities of CsIL-17C, CsIL-17D, and CsIL-17F, but not CsIL-17Fl, were modulated to significant extents by lipopolysaccharide, PolyI:C, and PMA. This study provides the first evidence that in teleost, different IL-17 members differ in expression pattern and promoter activity. PMID- 26364741 TI - Repeated handling compromises the immune suppression and improves the disease resistance in overwintering channel catfish (Ictalurus punctatus). AB - In winter, fish have suppressed immune functions and are susceptible to bacteria or virus which may lead to a high mortality. It is necessary to improve the immune response and disease resistance for overwintering fish. A recent study suggested that repeated handling increased the innate immune mechanisms and disease resistance in Senegalese sole. Therefore, the present study tested the hypothesis that appropriate repeated handling could compromise the immune depression and increase the disease resistance in channel catfish over winter. The experiment was carried out in field cages from Nov. 2012 to April 2013. Before the experiment, 35 fish with an average weight of 188.4 g were randomly assigned to one of six cages (2 m * 2 m * 2 m). Three cages were designed as the control group and did not receive any interfere. Fish in the other three cages received a weekly repeated handling of an air exposure for 5 min. Fish were not fed over winter. At the end of the trial, fish were challenged with Aeromonas hydrophila at a dose of 5.6 * 10(8) CFU ml(-1). The results showed that final body weight was not changed between groups. The spleen somatic index increased while the head kidney somatic index decreased in the unhandled fish after bacterial challenge, but these indices were not significantly changed in the repeated handled fish. Plasma cortisol levels in the control fish were induced at 6 h post challenge and then declined to the normal levels. However, plasma cortisol levels in the repeated handled fish did not show any significant change after bacteria challenge. The reduced inducement of heat shock protein 70 (HSP70) expression by repeated handling was observed in fish post bacterial challenge. After overwintering, repeated handled fish exhibited increased catalase (CAT) activities and reduced malondialdehyde (MDA) contents. Plasma total antioxidant capacity (TAOC), CAT and superoxide dismutase (SOD) activities of channel catfish were enhanced by repeated handling post bacterial challenge. The enhanced up regulation of Interleukin 8 (IL8), IL1beta-a, IL1beta-b together with the immune related genes of Toll-like receptor 2 (TLR2), TLR3, nucleotide-binding oligomerization domain 1 (NOD1) and NOD2 by repeated handling was found in catfish after bacterial challenge. The present results indicated that a combination of signaling pathways through TLRs and NODs was involved in the innate immune response of the overwintering repeated handled channel catfish against invading bacteria. PMID- 26364742 TI - A short-type peptidoglycan recognition protein from tongue sole (Cynoglossus semilaevis) promotes phagocytosis and defense against bacterial infection. AB - Peptidoglycan recognition proteins (PGRPs) are members of the innate immune system that interact with bacteria by binding to bacterial peptidoglycan. In this study, we examined the expression and function of a short type of PGRP, CsPGRP SC2, from tongue sole (Cynoglossus semilaevis). CsPGRP-SC2 contains 164 amino acid residues and shares 54.5%-65.3% overall sequence identities with other teleost PGRPs. CsPGRP-SC2 possesses an amidase domain with a conserved zinc binding site. CsPGRP-SC2 expression occurred in multiple tissues and was upregulated by bacterial and viral infection. Purified recombinant CsPGRP-SC2 (rCsPGRP-SC2) was able to bind and agglutinate Gram-positive bacteria in a Zn(2+) dependent manner. rCsPGRP-SC2 enhanced the uptake of the bound bacteria by host phagocytes and reduced bacterial dissemination and colonization in host tissues. These results indicate that CsPGRP-SC2 is an innate immune factor that participates in host defense against bacterial infection. PMID- 26364743 TI - Research advances on potential neurotoxicity of quantum dots. AB - With rapid development of nanotechnology, quantum dots (QDs) as advanced nanotechnology products have been widely used in biological and biomedical studies, including neuroscience, due to their superior optical properties. In recent years, there has been intense concern regarding the toxicity of QDs with a growing number of studies. However, the knowledge of neurotoxic consequences of QDs applied in living organisms is lagging behind their development, while a potential risk of neurotoxicity arises if mass production of QDs leads to increased exposure and distribution in the nervous system. Owing to the quantum size effect of QDs, they are capable of crossing the blood-brain barrier or moving along neural pathways and entering the brain. Nevertheless, the interactions of QDs with cells and tissues in the central nervous system are not well understood. This review highlighted research advances on the neurotoxicity of QDs in the central nervous system, including oxidative stress injury, elevated cytoplasmic Ca(2+) levels and autophagy to damage in vitro neural cells, and impairments of synaptic transmission and plasticity as well as brain functions in tested animals, with the hope of throwing light on future research directions of QD neurotoxicity, which is a demanding topic that requires further exploration. PMID- 26364745 TI - Flow Analysis: A Novel Approach For Classification. AB - We suggest a novel approach for classification of flow analysis methods according to the conditions under which the mass transfer processes and chemical reactions take place in the flow mode: dispersion-convection flow methods and forced convection flow methods. The first group includes continuous flow analysis, flow injection analysis, all injection analysis, sequential injection analysis, sequential injection chromatography, cross injection analysis, multi-commutated flow analysis, multi-syringe flow injection analysis, multi-pumping flow systems, loop flow analysis, and simultaneous injection effective mixing flow analysis. The second group includes segmented flow analysis, zone fluidics, flow batch analysis, sequential injection analysis with a mixing chamber, stepwise injection analysis, and multi-commutated stepwise injection analysis. The offered classification allows systematizing a large number of flow analysis methods. Recent developments and applications of dispersion-convection flow methods and forced-convection flow methods are presented. PMID- 26364744 TI - Heart and Brain Interactions--the Akershus Cardiac Examination (ACE) 1950 Study Design. AB - OBJECTIVES: The aim of the Akershus Cardiac Examination (ACE) 1950 Study is to investigate the development and progression of cardiovascular and cerebrovascular disease (CVD/CeVD) in an extensively characterized age cohort of middle-aged subjects with longitudinal long-term follow-up. DESIGN: The ACE 1950 Study is a prospective, population-based, age-cohort study of all men and women born in 1950 in Akershus County, Norway. The study involves a comprehensive baseline examination, especially for CVD/CeVD, including advanced ultrasound imaging and biobanking ("deep phenotyping"). We expect to obtain an inclusion rate of > 60% from the total study population of 5,827 eligible subjects. Enrollment will be completed during 2015. CONCLUSIONS: The ACE 1950 Study will have potential to generate new and relevant insight into identification of subclinical disease progression. Extensive phenotyping will enable identification of novel disease markers and mechanisms for subclinical disease, which can prove important for future disease prevention. PMID- 26364746 TI - Improved quorum sensing capacity by culturing Vibrio harveyi in microcapsules. AB - Microcapsule entrapped low density cells with culture (ELDCwc), different from free cell culture, conferred stronger stress resistance and improved cell viability of microorganisms. In this paper, the quorum sensing (QS) system of Vibrio harveyi was used to investigate changes when cells were cultured in microcapsules. Cells in ELDCwc group grew into cell aggregates, which facilitated cell-cell communication and led to increased bioluminescence intensity. Moreover, the luxS-AI-2 system, a well-studied QS signal pathway, was detected as both luxS gene and the AI-2 signaling molecule, and the results were analyzed with respect to QS capacity of unit cell. The V. harveyi of ELDCwc also showed higher relative gene expression and stronger quorum sensing capacity when compared with free cells. In conclusion, the confined microcapsule space can promote the cell aggregates formation, reduce cell-cell communication distance and increase local concentration of signal molecule, which are beneficial to bacterial QS. PMID- 26364747 TI - Review: in vitro microvessel models. AB - A wide range of perfusable microvessel models have been developed, exploiting advances in microfabrication, microfluidics, biomaterials, stem cell technology, and tissue engineering. These models vary in complexity and physiological relevance, but provide a diverse tool kit for the study of vascular phenomena and methods to vascularize artificial organs. Here we review the state-of-the-art in perfusable microvessel models, summarizing the different fabrication methods and highlighting advantages and limitations. PMID- 26364748 TI - Mycophenolate mofetil for lupus nephritis: an update. AB - Renal disease in systemic lupus erythematosus carries significant morbidity and mortality. Intensive immunosuppression to dampen kidney inflammation timely and maintenance therapy to prevent renal flares is necessary to reduce the long-term risk of renal failure. Mycophenolate mofetil (MMF) has emerged to be the first line treatment of lupus nephritis for its better safety profile compared with cyclophosphamide. In controlled trials, MMF is non-inferior to cyclophosphamide for induction therapy but is superior to azathioprine as maintenance therapy. Although biologics have shown promise in refractory lupus nephritis, combining MMF with a number of novel biological agents does not enhance the therapeutic efficacy. Recently, low-dose combination of MMF and tacrolimus has been shown to be more efficacious than intravenous pulse cyclophosphamide in inducing remission of lupus nephritis in Chinese patients. Therapeutic monitoring of the serum mycophenolic acid level to enhance the efficacy of MMF in lupus nephritis is being explored. PMID- 26364749 TI - Criteria for Applying the Lucas-Washburn Law. AB - Spontaneous imbibition happens in many natural and chemical engineering processes in which the mean advancing front usually follows Lucas-Washburn's law. However it has been found that the scaling law does not apply in many cases. There have been few criteria to determine under what conditions the Washburn law works. The effect of gravity on spontaneous imbibition in porous media was investigated both theoretically and experimentally. The mathematical model derived analytically was used to calculate the imbibition rates in porous media with different permeabilities. The results demonstrated that the effect of gravity on spontaneous imbibition was governed by the hydraulic conductivity of the porous media (permeability of the imbibition systems). The criteria for applying the Lucas-Washburn law have been proposed. The effect of gravity becomes more apparent with the increase in permeability or with the decrease in CGR number (the ratio of capillary pressure to gravity forces) and may be ignored when the CGR number is less than a specific value N(*)(cg) ? 3.0. The effect of gravity on imbibition in porous media can be modeled theoretically. It may not be necessary to conduct spontaneous imbibition experiments horizontally in order to exclude the effect of gravity, as has been done previously. PMID- 26364750 TI - Components of Intraflagellar Transport Complex A Function Independently of the Cilium to Regulate Canonical Wnt Signaling in Drosophila. AB - The development of multicellular organisms requires the precisely coordinated regulation of an evolutionarily conserved group of signaling pathways. Temporal and spatial control of these signaling cascades is achieved through networks of regulatory proteins, segregation of pathway components in specific subcellular compartments, or both. In vertebrates, dysregulation of primary cilia function has been strongly linked to developmental signaling defects, yet it remains unclear whether cilia sequester pathway components to regulate their activation or cilia-associated proteins directly modulate developmental signaling events. To elucidate this question, we conducted an RNAi-based screen in Drosophila non ciliated cells to test for cilium-independent loss-of-function phenotypes of ciliary proteins in developmental signaling pathways. Our results show no effect on Hedgehog signaling. In contrast, our screen identified several cilia associated proteins as functioning in canonical Wnt signaling. Further characterization of specific components of Intraflagellar Transport complex A uncovered a cilia-independent function in potentiating Wnt signals by promoting beta-catenin/Armadillo activity. PMID- 26364752 TI - Can consumers learn to ask three questions to improve shared decision making? A feasibility study of the ASK (AskShareKnow) Patient-Clinician Communication Model((r)) intervention in a primary health-care setting. AB - OBJECTIVE: To test the feasibility and assess the uptake and acceptability of implementing a consumer questions programme, AskShareKnow, to encourage consumers to use the questions '1. What are my options; 2. What are the possible benefits and harms of those options; 3. How likely are each of those benefits and harms to happen to me?' These three questions have previously shown important effects in improving the quality of information provided during consultations and in facilitating patient involvement. METHODS: This single-arm intervention study invited participants attending a reproductive and sexual health-care clinic to view a 4-min video-clip in the waiting room. Participants completed three questionnaires: (T1) prior to viewing the intervention; (T2) immediately after their consultation; and (T3) two weeks later. RESULTS: A total of 121 (78%) participants viewed the video-clip before their consultation. Eighty-four (69%) participants asked one or more questions, and 35 (29%) participants asked all three questions. For those making a decision, 55 (87%) participants asked one or more questions, while 27 (43%) participants asked all three questions. Eighty seven (72%) participants recommended the questions. After two weeks, 47 (49%) of the participants recalled the questions. CONCLUSIONS: Enabling patients to view a short video-clip before an appointment to improve information and involvement in health-care consultations is feasible and led to a high uptake of question asking in consultations. PRACTICE IMPLICATIONS: This AskShareKnow programme is a simple and feasible method of training patients to use a brief consumer-targeted intervention that has previously shown important effects in improving the quality of information provided during consultations and in facilitating patient involvement and use of evidence-based questions. PMID- 26364753 TI - Toxicological evaluation of ferrous N-carbamylglycinate chelate: Acute, Sub-acute toxicity and mutagenicity. AB - Iron is an essential trace element that is vital important in various biological process. A deficiency in iron could induce public health problem e.g. anaemia, while an overload could induce ROS production, lipid peroxidation and DNA bases modifications. In the present study, a new iron fortifier was synthesized, and its acute/sub-acute toxicity was investigated. According to the improved Karber's method, the median lethal dose (LD50) of the ferrous N-carbamylglycinate in SD rat was 3.02 g/kg and the 95% confidence intervals were between 2.78 and 3.31 g/kg. No biologically significant or test substance-related differences were observed in body weights, feed consumption, clinical signs, organ weights, histopathology, ophthalmology, hematology, and clinical chemistry parameters in any of the treatment groups of ferrous N-carbamylglycinate at target concentrations corresponding to 150, 300, and 600 mg/kg/day for 28 days. The no observed adverse effect level (NOAEL) for ferrous N-carbamylglycinate was at least 600 mg/kg b.w. day in rats. In addition, no evidence of mutagenicity was found, either in vitro in bacterial reverse mutation assay or in vivo in mice bone marrow micronucleus assay and sperm shape abnormality assay. On the basis of our findings, we conclude that ferrous N-carbamylglycinate is a low-toxic substance with no genotoxicity. PMID- 26364751 TI - Identification of Happyhour/MAP4K as Alternative Hpo/Mst-like Kinases in the Hippo Kinase Cascade. AB - In Drosophila and mammals, the canonical Hippo kinase cascade is mediated by Hpo/Mst acting through the intermediary kinase Wts/Lats to phosphorylate the transcriptional coactivator Yki/YAP/TAZ. Despite recent reports linking Yki/YAP/TAZ activity to the actin cytoskeleton, the underlying mechanisms are poorly understood and/or controversial. Using Drosophila imaginal discs as an in vivo model, we show that Wts, but not Hpo, is genetically indispensable for cytoskeleton-mediated subcellular localization of Yki. Through a systematic screen, we identify the Ste-20 kinase Happyhour (Hppy) and its mammalian counterpart MAP4K1/2/3/5 as an alternative kinase that phosphorylates the hydrophobic motif of Wts/Lats in a similar manner as Hpo/Mst. Consistent with their redundant function as activating kinases of Wts/Lats, combined loss of Hpo/Mst and Hppy/MAP4K abolishes cytoskeleton-mediated regulation of Yki/YAP subcellular localization, as well as YAP cytoplasmic translocation induced by contact inhibition. These Hpo/Mst-like kinases provide an expanded view of the Hippo kinase cascade in development and physiology. PMID- 26364754 TI - Comparison of residents' pesticide exposure with predictions obtained using the UK regulatory exposure assessment approach. AB - The UK regulatory methods currently used for estimating residents' potential pesticide exposure were assessed to determine whether they provide sufficiently conservative estimates. A non-random sample of 149 residents living within 100 m of fields where pesticides were sprayed provided first morning void urine samples one and/or two days after spraying. Using farmers' spray information, regulatory exposure assessment (REA) models were applied to estimate potential pesticide intake among residents, with a toxicokinetic (TK) model used to estimate urinary biomarker concentrations in the mornings of the two days following the spray. These were compared with actual measured urinary biomarker concentrations obtained following the spray applications. The study focused on five pesticides (cypermethrin, penconazole, captan, chlorpyrifos and chlormequat). All measured cypermethrin urinary biomarker levels were lower than the REA-predicted concentrations. Over 98% and 97% of the measured urinary biomarker concentrations for penconazole and captan respectively were lower than the REA-predicted exposures. Although a number of the chlorpyrifos and chlormequat spray-related urinary biomarker concentrations were greater than the predictions, investigation of the background urinary biomarker concentrations suggests these were not significantly different from the levels expected had no pesticide spraying occurred. The majority of measured concentrations being well below the REA predicted concentrations indicate that, in these cases, the REA is sufficiently conservative. PMID- 26364755 TI - ECG signatures of psychological stress. AB - Psychological stress can lead to atrial and ventricular arrhythmias, but the physiological pathways have not been fully elucidated. Signal processing techniques can provide insight into electrophysiological mechanisms of stress induced arrhythmia. T-wave alternans, as well as other ECG measures of heterogeneity of repolarization, increases with emotional and cognitive stress in the laboratory setting, and may also in "real life" settings. In the atrium, stress impacts components of the signal-averaged ECG. These changes suggest mechanisms by which everyday stressors can lead to arrhythmia. PMID- 26364756 TI - Alleviating Pressure on Water Resources: A new approach could be attempted. AB - Water and food safety are two major challenges which the world faces today. Traditional water management focuses on the reduction of water use through improvements in water saving technologies. However, quantitative research is needed to evaluate the effects of changing food consumption patterns on water resources. Here we report the water saving effects of changing diet pattern of the major crops and animal products in mainland China. By using the concepts of water footprint (WF) per weight unit and per calorie unit, provided by 13 primary crop and animal products, the WFs of the 13 agricultural products in each province are compared, and their water/energy conversion efficiencies are analyzed. Then, impacts of different scenarios of changing diet pattern on water consumption were explored. Results show that there are obvious differences between the WF per weight and calorie unit provided by crop and animal products due to the nutritional properties of the agricultural products. Promoting water savings from the food consumption side could give a positive feedback on water consumption. Scenario analysis of adjustments to the diet pattern proves that it is potentially feasible to reach the objective of alleviating stress on water resources while guaranteeing nutritional value of the residents. PMID- 26364757 TI - Characterization of the virulence of Cryptococcus neoformans strains in an insect model. PMID- 26364758 TI - Role of CCN2 in Amino Acid Metabolism of Chondrocytes. AB - CCN2/connective tissue growth factor (CTGF) is a multi-functional molecule that promotes harmonized development and regeneration of cartilage through its matricellular interaction with a variety of extracellular biomolecules. Thus, deficiency in CCN2 supply profoundly affects a variety of cellular activities including basic metabolism. A previous study showed that the expression of a number of ribosomal protein genes was markedly enhanced in Ccn2-null chondrocytes. Therefore, in this study, we analyzed the impact of CCN2 on amino acid and protein metabolism in chondrocytes. Comparative metabolome analysis of the amino acids in Ccn2-null and wild-type mouse chondrocytes revealed stable decreases in the cellular levels of all of the essential amino acids. Unexpectedly, uptake of such amino acids was rather enhanced in Ccn2-null chondrocytes, and the addition of exogenous CCN2 to human chondrocytic cells resulted in decreased amino acid uptake. However, as expected, amino acid consumption by protein synthesis was also accelerated in Ccn2-null chondrocytes. Furthermore, we newly found that expression of two genes encoding two glycolytic enzymes, as well as the previously reported Eno1 gene, was repressed in those cells. Considering the impaired glycolysis and retained mitochondrial membrane potential in Ccn2-null chondrocytes, these findings suggest that Ccn2 deficiency induces amino acid shortage in chondrocytes by accelerated amino acid consumption through protein synthesis and acquisition of aerobic energy. Interestingly, CCN2 was found to capture such free amino acids in vitro. Under physiological conditions, CCN2 may be regulating the levels of free amino acids in the extracellular matrix of cartilage. PMID- 26364759 TI - [5]Radialene. AB - The [n]radialenes are a unique family of fundamental [n]-membered carbocyclic structures with radiating alkenes, which have attracted significant synthetic and theoretical attention. Whereas [3]-, [4]-, and [6]radialenes have been prepared and studied, all efforts to synthesize the five-membered ring compound have thus far met with failure. Here we describe the first synthesis of the fundamental hydrocarbon [5]radialene, C10H10. Our approach was a departure from previous radialene syntheses in that it utilized a low-temperature decomplexation of a stable organometallic compound, rather than high-temperature elimination or rearrangement. Our strategy was guided by analysis of previous radialene syntheses, which indicated rapid decomposition in oxygen, and ab initio calculations, which revealed an extraordinary susceptibility of [5]radialene to undergo Diels-Alder dimerization/polymerization. The origin of this susceptibility was traced to a small distortion energy associated with the formation of the transition structure geometry from the relaxed reactant monomers and to a narrow HOMO-LUMO gap. PMID- 26364760 TI - Visual function among commercial vehicle drivers in the central region of Ghana. AB - AIM: To determine the relationship between some visual functions: colour vision defects, abnormal stereopsis, visual acuity and the occurrence of road traffic accident (RTAs) among commercial vehicle drivers in the central region of Ghana, and to assess their knowledge of these anomalies. METHOD: A descriptive cross sectional study employing a multi-stage random sampling approach was conducted in the major commercial towns within the central region of Ghana. Participants were taken through a comprehensive eye examination after the administration of a structured questionnaire. RESULTS: 520 male commercial vehicle drivers were enrolled for this study with a mean age of 39.23 years +/-10.96 years and mean visual acuity of 0.02+/-0.08 logMAR. Protans were more likely to be involved in RTAs (chi(2)=6.194, p=0.034). However, there was no statistically significant association between abnormal stereopsis (OR=0.89 95% CI: 0.44-1.80, p=0.56), poor vision due to refractive error (chi(2)=3.090, p=0.388) and the occurrence of RTAs. While 86.9% were aware of abnormal stereopsis, only 45% were aware of colour vision defects. There was a statistically significant association between stereopsis anomaly and colour vision defect (r=0.371, p<0.005). CONCLUSION: The study found an association between protanopia and RTAs but none between stereopsis anomalies, refractive errors and the occurrence of RTAs. Drivers were less knowledgeable on colour vision defects as compared to stereopsis anomalies. PMID- 26364761 TI - A novel navigation system for maxillary positioning in orthognathic surgery: Preclinical evaluation. AB - Appropriate positioning of the maxilla is critical in orthognathic surgery. As opposed to splint-based positioning, navigation systems are versatile and appropriate in assessing the vertical dimension. Bulk and disruption to the line of sight are drawbacks of optical navigation systems. Our aim was to develop and assess a novel navigation system based on electromagnetic tracking of the maxilla, including real-time registration of head movements. Since the software interface has proved to greatly influence the accuracy of the procedure, we purposely designed and evaluated an original, user-friendly interface. A sample of 12 surgeons had to navigate the phantom osteotomized maxilla to eight given target positions using the software we have developed. Time and accuracy (translational error and angular error) were compared between a conventional and a navigated session. A questionnaire provided qualitative evaluation. Our system definitely allows a reduction in variability of time and accuracy among different operators. Accuracy was improved in all surgeons (mean terror difference = 1.11 mm, mean aerror difference = 1.32 degrees ). Operative time was decreased in trainees. Therefore, they would benefit from such a system that could also serve for educational purposes. The majority of surgeons who strongly agreed that such a navigation system would prove very helpful in complex deformities, also stated that it would be helpful in everyday orthognathic procedures. PMID- 26364762 TI - Clinical predictors of oral leukoplakia recurrence following CO2 laser vaporization. AB - OBJECTIVE: The objective of this study was to determine whether risk of early leukoplakia recurrence (within 3 months) following carbon dioxide (CO2) laser removal varies by clinical characteristics including lesion size, site and accessibility of margins. MATERIALS AND METHODS: A retrospective cohort study included patients with oral leukoplakia who had their first CO2 laser surgery for removal of oral leukoplakia between 2005 and 2010 at the UCSF oral medicine clinic. Twenty-six patients with 32 separate lesions met the eligibility criteria after a clinic database search was followed by review of clinical notes and biopsy reports from existing patient charts. Data analysis included computation of summary statistics, and logistic regression analyses to evaluate recurrence of leukoplakia by clinical characteristics of the lesions. RESULTS: Patient data and the characteristics of lesions were evaluated as possible predictors of early recurrence following laser removal; these included age, sex, duration, size, appearance and histopathology of the lesion. The only one that reached statistical significance was poor accessibility of the margins of the lesion (vs. good accessibility, OR = 24.57 (95% CI: 1.59-16.68), p = 0.016); the probability for trend for good, questionable, and poor accessibility was 0.0028. This finding remained significant after controlling for age, sex, duration and size of lesion. Four out of five lesions with poor accessibility showed recurrence at 3 months. Of these, three involved the gingiva and one the lateral tongue. CONCLUSIONS: This study has identified poor accessibility of the lesion margins as a predictor for early recurrence of leukoplakia following laser removal. Other variables evaluated did not reach statistical significance, possibly due to lack of power. PMID- 26364763 TI - Mitochondrial dynamics and their intracellular traffic in porcine oocytes. AB - Meiotic maturation of oocytes requires a variety of ATP-dependent reactions, such as germinal vesicle breakdown, spindle formation, and rearrangement of plasma membrane structure, which is required for fertilization. Mitochondria are accordingly expected be localized to subcellular sites of energy utilization. Although microtubule-dependent cellular traffic for mitochondria has been studied extensively in cultured neuronal (and some other somatic) cells, the molecular mechanism of their dynamics in mammalian oocytes at different stages of maturation remains obscure. The present work describes dynamic aspects of mitochondria in porcine oocytes at the germinal vesicle stage. After incubation of oocytes with MitoTracker Orange followed by centrifugation, mitochondria enriched ooplasm was obtained using a glass needle and transferred into a recipient oocyte. The intracellular distribution of the fluorescent mitochondria was then observed over time using a laser scanning confocal microscopy equipped with an incubator. Kinetic analysis revealed that fluorescent mitochondria moved from central to subcortical areas of oocytes and were dispersed along plasma membranes. Such movement of mitochondria was inhibited by either cytochalasin B or cytochalasin D but not by colcemid, suggesting the involvement of microfilaments. This method of visualizing mitochondrial dynamics in live cells permits study of the pathophysiology of cytoskeleton-dependent intracellular traffic of mitochondria and associated energy metabolism during meiotic maturation of oocytes. PMID- 26364764 TI - High e+/e- Ratio Dense Pair Creation with 10(21)W.cm(-2) Laser Irradiating Solid Targets. AB - We report results of new pair creation experiments using ~100 Joule pulses of the Texas Petawatt Laser to irradiate solid gold and platinum targets, with intensities up to ~1.9 * 10(21) W.cm(-2) and pulse durations as short as ~130 fs. Positron to electron (e+/e-) ratios >15% were observed for many thick disk and rod targets, with the highest e+/e- ratio reaching ~50% for a Pt rod. The inferred pair yield was ~ few *10(10) with emerging pair density reaching ~10(15)/cm(3) so that the pair skin depth becomes < pair jet transverse size. These results represent major milestones towards the goal of creating a significant quantity of dense pair-dominated plasmas with e+/e- approaching 100% and pair skin depth ? pair plasma size, which will have wide-ranging applications to astrophysics and fundamental physics. PMID- 26364765 TI - Double-blind placebo-controlled study of bepotastine besilate in pediatric patients with perennial allergic rhinitis. AB - BACKGROUND: Although second-generation antihistamines, such as bepotastine besilate, are recommended as a first-line treatment option for adult perennial allergic rhinitis (PAR), few non-sedating second-generation antihistamines are safe for children. OBJECTIVE: A double-blind, placebo-controlled, comparative study of 473 pediatric PAR patients (7 - 15 years old) to determine the superiority and safety of bepotastine besilate (10 mg twice daily) relative to placebo for improved total and individual nasal symptom scores compared with baseline. RESEARCH DESIGN AND METHODS: Subjects were randomized to placebo (n = 233) or bepotastine besilate (n = 240, 10 mg orally twice daily for 2 weeks). Interference of daily life by PAR was assessed by measuring change in individual nasal symptom scores from baseline. RESULTS: Bepotastine besilate was superior to placebo in terms of total nasal symptom scores, with improved overall nasal symptoms of PAR compared with baseline values. Subgroup analyses demonstrated bepotastine besilate was effective irrespective of age, sex or body weight. No clinically significant adverse drug reactions often observed with first generation antihistamines were reported and no difference in adverse events between groups was observed. CONCLUSIONS: Bepotastine besilate is effective and safe for pediatric PAR patients aged 7 - 15 years, and has a significant clinical impact on PAR. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01861522 ( https://clinicaltrials.gov/ct2/show/NCT01861522 ). PMID- 26364766 TI - Care for infants born at 23 weeks gestational age: 5 years' experience from a large medical center. AB - OBJECTIVES: Assessing parental choice regarding care of infants born at 23 weeks' gestation. METHODS: Neonatal records review. RESULTS: During 2010-2014, of 26 births (33 infants), 13 families (17 newborns) conceded comfort care only with no survivors, while 13 families (16 babies) requested full medical care and three survived. With birth year, gender, multi-fetal pregnancy, assisted reproductive technology, religious background and specialization of physician counseling at delivery as independent variables, none significantly affected parental decision; yet, that decision impacted outcome. CONCLUSIONS: Parental choice regarding infants born at 23 weeks' gestation cannot be predicted from demographics; counseling should concentrate on local experience/outcome. PMID- 26364768 TI - Identification of key residues in Debaryomyces hansenii carbonyl reductase for highly productive preparation of (S)-aryl halohydrins. AB - Key residues of Debaryomyces hansenii carbonyl reductase in the determination of the reducing activity towards aryl haloketones were identified through combinatorial mutation of conserved residues. This study provides a green and efficient biocatalyst for the synthesis of (S)-aryl halohydrins. PMID- 26364767 TI - Familial recurrences of FOXG1-related disorder: Evidence for mosaicism. AB - FOXG1-related disorders are caused by heterozygous mutations in FOXG1 and result in a spectrum of neurodevelopmental phenotypes including postnatal microcephaly, intellectual disability with absent speech, epilepsy, chorea, and corpus callosum abnormalities. The recurrence risk for de novo mutations in FOXG1-related disorders is assumed to be low. Here, we describe three unrelated sets of full siblings with mutations in FOXG1 (c.515_577del63, c.460dupG, and c.572T > G), representing familial recurrence of the disorder. In one family, we have documented maternal somatic mosaicism for the FOXG1 mutation, and all of the families presumably represent parental gonadal (or germline) mosaicism. To our knowledge, mosaicism has not been previously reported in FOXG1-related disorders. Therefore, this report provides evidence that germline mosaicism for FOXG1 mutations is a likely explanation for familial recurrence and should be considered during recurrence risk counseling for families of children with FOXG1 related disorders. PMID- 26364769 TI - Integrating regional conservation priorities for multiple objectives into national policy. AB - Multinational conservation initiatives that prioritize investment across a region invariably navigate trade-offs among multiple objectives. It seems logical to focus where several objectives can be achieved efficiently, but such multi objective hotspots may be ecologically inappropriate, or politically inequitable. Here we devise a framework to facilitate a regionally cohesive set of marine protected areas driven by national preferences and supported by quantitative conservation prioritization analyses, and illustrate it using the Coral Triangle Initiative. We identify areas important for achieving six objectives to address ecosystem representation, threatened fauna, connectivity and climate change. We expose trade-offs between areas that contribute substantially to several objectives and those meeting one or two objectives extremely well. Hence there are two strategies to guide countries choosing to implement regional goals nationally: multi-objective hotspots and complementary sets of single-objective priorities. This novel framework is applicable to any multilateral or global initiative seeking to apply quantitative information in decision making. PMID- 26364770 TI - Current aspects of auxin biosynthesis in plants. AB - Auxin is an important plant hormone essential for many aspects of plant growth and development. Indole-3-acetic acid (IAA) is the most studied auxin in plants, and its biosynthesis pathway has been investigated for over 70 years. Although the complete picture of auxin biosynthesis remains to be elucidated, remarkable progress has been made recently in understanding the mechanism of IAA biosynthesis. Genetic and biochemical studies demonstrate that IAA is mainly synthesized from l-tryptophan (Trp) via indole-3-pyruvate by two-step reactions in Arabidopsis. While IAA is also produced from Trp via indole-3-acetaldoxime in Arabidopsis, this pathway likely plays an auxiliary role in plants of the family Brassicaceae. Recent studies suggest that the Trp-independent pathway is not a major route for IAA biosynthesis, but they reveal an important role for a cytosolic indole synthase in this pathway. In this review, I summarize current views and future prospects of IAA biosynthesis research in plants. PMID- 26364771 TI - The Toll of Too Much Technology on Teens' Mental Health. AB - Technology is here to stay, and forbidding adolescents to access electronic media may not be a sustainable solution. Pediatric health care providers should include technology use and the parents' knowledge of the child's technology use, in their screening practices with patients. With the guidance of pediatric nurses, parents and children together can collaborate on ways to maximize the benefits of technology and decrease its risks. PMID- 26364772 TI - Cough ability measurements and recurrent respiratory symptoms in individuals with Ataxia Telangiectasia. AB - OBJECTIVES: Ataxia-Telangiectasia (A-T) individuals often present with respiratory muscle weakness, causing recurrent respiratory system infections, asthma-like symptoms, and chronic cough life-threatening events. The cough flow volume maneuver may reveal powerless airflow needed for efficient cough. The study aims to explore cough ability in relation to the flow/volume maneuver. METHODS: Data collected retrospectively from clinical charts of 35 A-T patients (age 12.7 +/- 4.9 years) included forced expiratory and cough flow/volume maneuvers performed on the same day. Analysis compared among the maneuvers matching indices, numbers of cough-spikes, flow rate decay, and the reference data of similar ages. Adjusted to age, BMI, and number of hospitalizations prior to the tests, values were correlated with the cough indices. RESULTS: Cough peak flow (C-PF) was propagated within 90 +/- 20 ms compared with peak expiratory flow (PEF > 200 ms). C-PF measured values were higher than expiratory peak-flow measured values (3.27 +/- 1.53 L/s versus 3.02 +/- 1.52 L/s, respectively, but C PF (%predicted) values were significantly lower than expiratory peak-flow (%predicted) (46 +/- 15 versus 68 +/- 20 %predicted, respectively, p < 0.002). The number of spikes/maneuver was low when compared with reference (2.0 +/- 0.8 versus 6-12 spikes) and cough vital-capacity was lower than expiratory vital capacity (0.95 +/- 0.43 versus 1.03 +/- 0.47; p < 0.01). Inefficient C-PF was more prevalent in patients suffering from recurrent respiratory illness. The length of wheelchair confinement duration mostly influenced the C-VC level. CONCLUSIONS: The cough flow-volume curve can be applied as a method to follow cough ability in patients with A-T who showed a significantly reduced cough capacity. Further studies are needed to establish if the findings may aid decisions regarding cough assistance. PMID- 26364773 TI - Distinguishing professionalism and heroism when disaster strikes. PMID- 26364774 TI - Guest editorial: Reassessing animal research ethics. PMID- 26364775 TI - The ethical challenges of animal research. AB - In 1966, Henry K. Beecher published an article entitled "Ethics and Clinical Research" in the New England Journal of Medicine, which cited examples of ethically problematic human research. His influential paper drew attention to common moral problems such as inadequate attention to informed consent, risks, and efforts to provide ethical justification. Beecher's paper provoked significant advancements in human research policies and practices. In this paper, we use an approach modeled after Beecher's 1966 paper to show that moral problems with animal research are similar to the problems Beecher described for human research. We describe cases that illustrate ethical deficiencies in the conduct of animal research, including inattention to the issue of consent or assent, incomplete surveys of the harms caused by specific protocols, inequitable burdens on research subjects in the absence of benefits to them, and insufficient efforts to provide ethical justification. We provide a set of recommendations to begin to address these deficits. PMID- 26364777 TI - Necessary conditions for morally responsible animal research. AB - In this article, we present three necessary conditions for morally responsible animal research that we believe people on both sides of this debate can accept. Specifically, we argue that, even if human beings have higher moral status than nonhuman animals, animal research is morally permissible only if it satisfies (1) an expectation of sufficient net benefit, (2) a worthwhile-life condition, and (3) a no-unnecessary-harm/qualified-basic-needs condition. We then claim that, whether or not these necessary conditions are jointly sufficient for justified animal research, they are relatively demanding, with the consequence that many animal experiments may fail to satisfy them. PMID- 26364776 TI - The flaws and human harms of animal experimentation. AB - Nonhuman animal ("animal") experimentation is typically defended by arguments that it is reliable, that animals provide sufficiently good models of human biology and diseases to yield relevant information, and that, consequently, its use provides major human health benefits. I demonstrate that a growing body of scientific literature critically assessing the validity of animal experimentation generally (and animal modeling specifically) raises important concerns about its reliability and predictive value for human outcomes and for understanding human physiology. The unreliability of animal experimentation across a wide range of areas undermines scientific arguments in favor of the practice. Additionally, I show how animal experimentation often significantly harms humans through misleading safety studies, potential abandonment of effective therapeutics, and direction of resources away from more effective testing methods. The resulting evidence suggests that the collective harms and costs to humans from animal experimentation outweigh potential benefits and that resources would be better invested in developing human-based testing methods. PMID- 26364778 TI - The upper limits of pain and suffering in animal research. AB - The control of risk and harm in human research often calls for the establishment of upper limits of risk of pain, suffering, and distress that investigators must not exceed. Such upper limits are uncommon in animal research, in which limits of acceptability are usually left to the discretion of individual investigators, institutions, national inspectors, or ethics review committees. We here assess the merits of the European Directive 2010/63/EU on the Protection of Animals Used for Scientific Purposes and its accompanying instruments, such as guides and examples. These documents present a body of legislation governing animal research in the European Union. We argue that the directive supplies a promising approach, but one in need of revision. We interpret the directive's general conception of upper limits and show its promise for the establishment of high-quality policies. We provide a moral rationale for such policies, address the problem of justified exceptions to established upper limits, and show when causing harm is and is not wrongful. We conclude that if the standards we propose for improving the directive are not realized in the review of research protocols, loose and prejudicial risk-benefit assessments may continue to be deemed sufficient to justify morally questionable research. However, a revised EU directive and accompanying instruments could have a substantial influence on the ethics of animal research worldwide, especially in the development of morally sound legal frameworks. PMID- 26364779 TI - Ending the use of animals in toxicity testing and risk evaluation. AB - This article discusses the use of animals for the safety testing of chemicals, including pharmaceuticals, household products, pesticides, and industrial chemicals. It reviews changes in safety testing technology and what those changes mean from the perspective of industrial innovation, public policy and public health, economics, and ethics. It concludes that the continuing use of animals for chemical safety testing should end within the decade as cheaper, quicker, and more predictive technologies are developed and applied. PMID- 26364780 TI - Is there a role for assent or dissent in animal research? AB - Current regulations and widely accepted principles for animal research focus on minimizing the burdens and harms of research on animals. However, these regulations and principles do not consider a possible role for assent or dissent in animal research. Should investigators solicit the assent or respect the dissent of animals who are used in research, and, if so, under what circumstances? In this article we pursue this question and outline the relevant issues that bear on the answer. We distinguish two general reasons for respecting the preferences of research participants regarding whether they participate in research-welfare-based reasons and agency-based reasons. We argue that there are welfare-based reasons for researchers to consider, and in some cases respect, the dissent of all animals used in research. After providing a brief account of the nature of agency-based reasons, we argue that there is good reason to think that these reasons apply to at least chimpanzees. We argue that there is an additional reason for researchers to respect the dissent-and, when possible, solicit the assent-of any animal to whom agency-based reasons apply. PMID- 26364781 TI - Unrequited love hurts. PMID- 26364782 TI - On love, ethics, technology, and neuroenhancement. PMID- 26364783 TI - Two concerns about the medicalization of love. PMID- 26364784 TI - A responsibility to chemically help patients with relationships and love? PMID- 26364785 TI - Trivial love. PMID- 26364786 TI - Validation of a New Instrument for Self-care in Spanish Palliative Care Professionals Nationwide. AB - Self-care is a cornerstone issue for those who deal with stressful events, as it is the case of palliative care professionals. It has been related to awareness, coping with death and quality of life, among others, but no measurement instruments have been used in palliative care professionals. This research presents and validates a brief new measure with clinical and psychometric good properties, called Professional Self-Care Scale (PSCS). The PSCS assesses professionals' self-care in three areas: physical self-care, inner self-care, and social self-care. Data come from a cross-sectional survey in a sample of 385 professionals of palliative care. The Mindful Attention Awareness Scale, the Coping with Death Scale, and the Professional's Quality of Life measure were also used. Results of the CFA showed adequate fit (chi2(24, N = 385) = 140.66, p < .01; CFI = .91; GFI = .93; SRMR = .09; and RMSEA = .10). Evidence pointed better reliability indices for the 3-item physical and inner factors of self-care than for the social dimension (Rho and GLB of .64, .90, and .57, respectively). Evidence regarding validity was consistent with previous literature. When levels of self-care were examined, women showed higher levels of inner and social self care (F(3, 371) = 3.19, p = .02, eta2 = .03, as also did psychologists when compared to doctors and nurses (F(9, 1074) = 2.00, p = .04, eta2 = .02. The PSCS has shown adequate psychometric properties, and thus it could be used as diagnostic instrument when studying professionals' health. PMID- 26364787 TI - Novel pulmonary rehabilitation approach in a 46-year-old female with significant decline in lung and functional status following H1N1. AB - INTRODUCTION: Pulmonary rehabilitation (PR) is an established therapeutic intervention for improving limb muscle dysfunction, reducing morbidity and mortality in a variety of chronic lung conditions. Providers are instrumental in improving success by optimizing disease management, minimizing barriers and tailoring a program to meet the patient's goals and functional needs. CASE REPORT: We present a case of a young woman with mild asthma who developed severe chronic obstructive pulmonary disease following H1N1. She remained limited in instrumental activities of daily living following traditional PR but participated in therapeutic horseback riding with notable improvement in functional capacity and emotional well-being. CONCLUSIONS: There is a growing body of knowledge on the benefits of PR but little is known about the physiologic and psychological benefits of other forms of exercise such as horseback riding. This case highlights the importance of individualizing care and identifies a novel area of research to be explored. PMID- 26364788 TI - Comparisons of complementary feeding indicators among children aged 6-23 months in Anglophone and Francophone West African countries. AB - Stunting, a consequence of suboptimal complementary feeding practices, continues to be a significant public health problem in West Africa. This paper aimed to compare rates of complementary feeding indicators among children aged 6-23 months between four Anglophone and seven Francophone West African countries. The data used for this study were the most recent Demographic and Health Surveys of the various countries, namely Ghana, Liberia, Nigeria, Sierra Leone (Anglophone countries), Benin, Burkina Faso, Cote d'Ivoire, Guinea, Mali, Niger and Senegal (Francophone countries) conducted between 2006 and 2013. The analyses were limited to last-born children aged 6-23 months and covered 34 999 children: 12 623 in the Anglophone countries and 22 376 children in the Francophone countries. Complementary feeding indicators were examined using the method proposed by the World Health Organization (WHO) in 2008. Introduction of solid, semi-solid or soft foods among children aged 6-23 months in the Anglophone countries ranged from 55.3% (Liberia) to 72.6% (Ghana). The corresponding rates for the Francophone countries ranged from 29.7% (Mali) to 65.9% (Senegal). The average rate of minimum dietary diversity for the Anglophone countries was 32.0% while that of the Francophone countries was only 10.6%. While the minimum meal frequency rates ranged between 42.0% (Sierra Leone) and 55.3% (Nigeria) for the Anglophone countries, the corresponding rates for the Francophone countries ranged between 25.1% (Mali) and 52.4% (Niger). Both the Anglophone and the Francophone countries reported alarmingly low rates of minimum acceptable diet, with the two groups of countries averaging rates of 19.9% (Anglophone) and 5.5% (Francophone). The rates of all four complementary feeding indicators across all the 11 countries fell short of the WHO's requirement for optimal complementary feeding practices. Intervention studies using cluster-randomised controlled trials are needed in order to improve the nutritional status of young children in West Africa. PMID- 26364789 TI - Determinants of suboptimal complementary feeding practices among children aged 6 23 months in four anglophone West African countries. AB - Suboptimal complementary feeding practices have a detrimental impact on a child's growth, health and development in the first two years of life. They lead to child malnutrition, which contributes to the high prevalence of stunting (38%) and underweight (28%) reported for children <5 years of age in Sub-Saharan Africa. This study analysed complementary feeding practices in four anglophone West African countries (Ghana, Liberia, Nigeria and Sierra Leone) using the most recent Demographic and Health Surveys. The study covered 12 623 children aged 6 23 months from four anglophone West African countries (Ghana: 822 children: Liberia: 1458 children, Nigeria: 8786 children and Sierra Leone: 1557 children). Four complementary feeding indicators were examined against a set of individual-, household- and community-level factors, using multiple regression analysis. Multivariate analyses found that lack of post-natal contacts with health workers, maternal illiteracy and geographical region were common determinants of delayed introduction of solid, semi-solid or soft foods across all four countries. Predictors for minimum dietary diversity, minimum meal frequency and minimum acceptable diet included children aged 6-11 months, administrative/geographical region, poorer household income and limited access to media. The authors recommend that the four anglophone West African countries studied should prioritise efforts to improve complementary feeding practices in order to reduce child morbidity and mortality. Interventional studies on complementary feeding should target those from poor and illiterate households. PMID- 26364790 TI - Determinants of suboptimal complementary feeding practices among children aged 6 23 months in seven francophone West African countries. AB - Suboptimal complementary feeding practices play a crucial role in the health and development of children. The objective of this research paper was to identify factors associated with suboptimal complementary feeding practices among children aged 6-23 months in seven francophone West African countries, namely, Benin, Burkina Faso, Cote d'Ivoire, Guinea, Mali, Niger and Senegal. This study covered 22 376 children aged 6-23 months from the seven countries surveyed (Benin: 3732 children; Burkina Faso: 4205 children; Cote d'Ivoire: 2109 children, Guinea: 1944 children, Mali: 3798 children, Niger: 3451 children and Senegal: 3137 children). The most recent Demographic and Health Survey datasets of the various countries were used as data sources. A set of individual-, household- and community-level factors were used to examine the four complementary feeding indicators. Multivariate analysis revealed that the youngest age bracket (6-11 months) of children, administrative/geographical region, mother's limited or non-access to the mass media, mothers' lack of contact with a health facility, rural residence, poor households and non-working mothers were the main factors associated with suboptimal complementary feeding in the countries surveyed. Our findings highlight the need to consider broader social, cultural and economic factors when designing child nutritional interventions. PMID- 26364792 TI - CH4 dissociation on Ni(111): a quantum dynamics study of lattice thermal motion. AB - Lattice thermal motion is of great importance because it has a significant effect on molecule activation on metal surfaces. Here, we present an in-depth quantum dynamics study of lattice thermal motion for methane dissociation on some static distorted Ni(111) surfaces based on an accurate, fourteen-dimensional potential energy surface fitted to ~10(5)ab initio energy points. Our study reproduces the tendency that the sticking probability of ground state methane increases (decreases) as the lattice atom moves upward (downward), and thus represents the first validation of the applicability of the energy-shifting scheme to polyatomic molecular gas-surface reactions. Furthermore, we improve on the linear model proposed by Jackson's group and introduce a new model that is applicable to a broad range of surface temperatures. PMID- 26364791 TI - The problem of suboptimal complementary feeding practices in West Africa: what is the way forward? AB - The objective of this paper was to review the policy implications of inadequate complementary feeding among children aged 6-23 months in West Africa. The review was undertaken from the initial results and findings from a series of studies on the comparison of complementary feeding indicators among children aged 6-23 months in four anglophone and seven francophone West African countries. It also examined a study of the determinants of suboptimal complementary feeding practices among children aged 6-23 months in those countries. Among the four complementary feeding indicators, it was only the introduction of solid, semi solid or soft foods that was adequate among children in all the West African countries surveyed. The rates of the other complementary feeding indicators were found to be inadequate in all countries surveyed, although relatively better among children in the anglophone countries. Alarmingly, low rates of minimum acceptable diet were reported among children from both the anglophone and the francophone countries. Infants 6-11 months of age, children living in poor households, administrative/geographical regional differences and mothers' access to the media were some of the common risk factors for optimal complementary feeding practices in these countries. Assessing complementary feeding indicators and determinants of suboptimal complementary feeding practices in these West African countries is crucial to improving infant and young child feeding practices. It is recommended that governments and stakeholders of the West African countries studied make greater efforts to improve these critical practices in order to reduce child morbidity and mortality in the West Africa sub region. Intervention studies on complementary feeding should target those socio demographic factors that pose risks to optimal complementary feeding. PMID- 26364794 TI - Waardenburg syndrome type IIE in a Japanese patient caused by a novel missense mutation in the SOX10 gene. PMID- 26364793 TI - Maternal and fetal exposure to parabens in a multiethnic urban U.S. population. AB - Fetal exposure to five parabens was investigated due to their endocrine disrupting potential and possible impact on fetal development. Body burdens occurring from real-world exposures were determined typically as total concentrations after conjugate hydrolysis in 181 maternal urine and 38 umbilical cord blood plasma samples from a multiethnic cohort of 185 predominantly-black, pregnant women recruited in Brooklyn, New York between 2007/9. For 33 participants, both sample types (maternal urine and cord blood) were available. Methyl- (MePB), ethyl- (EtPB), propyl- (PrPB), butyl- (BuPB), and benzylparaben (BePB) were detected in 100, 73.5, 100, 66.3 and 0.0% of the urine samples at median concentrations of 279, 1.44, 75.3, 0.39, and <0.02MUg/L, respectively. Median concentrations of MePB and PrPB were, respectively 4.4- and 8.7-fold higher compared to those reported previously for the general U.S. population (NHANES, 2005/6). Listed in the order above, the five parabens were detected in 97.4, 94.7, 47.4, 47.4, and 44.7% of cord blood plasma samples at median total concentrations of 25.0, 0.36, <0.27, <0.09, and <0.10MUg/L, respectively. Free MePB, EtPB, and PrPB were detected in a subset of cord blood plasma samples at, respectively, 3.9, 71.7, and 6.4% of their total concentrations, whereas free BuPB and BePB were not detected. Literature data and those reported here show the urban community studied here to rank highest in the world for MePB and PrPB exposure in pregnant women, whereas it ranks among the lowest for EtPB and BuPB. This study is the first to report the occurrence of parabens in human umbilical cord blood. Maternal exposure to parabens is widespread, and substantial differences were found to exist between communities and countries both in the spectrum and degree of paraben exposures. PMID- 26364795 TI - Self-assembling DNA hydrogel-based delivery of immunoinhibitory nucleic acids to immune cells. AB - Immunoinhibitory oligodeoxynucleotides (INH-ODNs) are promising inhibitors of Toll-like receptor 9 (TLR9) activation. To efficiently deliver INH-ODNs to TLR9 positive cells, we designed a Takumi-shaped DNA (Takumi) consisting of two partially complementary ODNs as the main component of a DNA hydrogel. Polyacrylamide gel electrophoresis showed that Takumi-containing INH-ODNs (iTakumi) and iTakumi-based DNA hydrogel (iTakumiGel) were successfully generated. Their activity was examined in murine macrophage-like RAW264.7 cells and DC2.4 dendritic cells by measuring tumor necrosis factor-alpha and interleukin-6 release after the addition of a TLR9 ligand (CpG ODN). Cytokine release was efficiently inhibited by the iTakumiGel. Flow cytometry analysis and confocal microscopy showed that cellular uptake of INH-ODN was greatly increased by the iTakumiGel. These results indicate that a Takumi-based DNA hydrogel is useful for the delivery of INH-ODNs to immune cells to inhibit TLR9-mediated hyperinduction of proinflammatory cytokines. From the Clinical Editor: Toll-like receptor 9 activation has been reported to be associated with many autoimmune diseases. DNA inhibition using oligodeoxynucleotides is one of the potential treatments. In this article, the authors described hydrogel-based platform for the delivery of the inhibitory oligodeoxynucleotides for enhanced efficacy. The positive findings could indicate a way for the future. PMID- 26364796 TI - Random Lasing with Systematic Threshold Behavior in Films of CdSe/CdS Core/Thick Shell Colloidal Quantum Dots. AB - While over the past years the syntheses of colloidal quantum dots (CQDs) with core/shell structures were continuously improved to obtain highly efficient emission, it has remained a challenge to use them as active materials in laser devices. Here, we report random lasing at room temperature in films of CdSe/CdS CQDs with different core/shell band alignments and extra thick shells. Even though the lasing process is based on random scattering, we find systematic dependencies of the laser thresholds on morphology and laser spot size. To minimize laser thresholds, optimizing the film-forming properties of the CQDs, proven by small-angle X-ray scattering, was found to be more important than the optical parameters of the CQDs, such as biexciton lifetime and binding energy or fluorescence decay time. Furthermore, the observed systematic behavior turned out to be highly reproducible after storing the samples in air for more than 1 year. These highly reproducible systematic dependencies suggest that random lasing experiments are a valuable tool for testing nanocrystal materials, providing a direct and simple feedback for further development of colloidal gain materials toward lasing in continuous wave operation. PMID- 26364797 TI - Ruxolitinib treatment for myelofibrosis: Efficacy and tolerability in routine practice. AB - Ruxolitinib has been shown in two randomized clinical trials to be effective in alleviating systemic symptoms and reducing spleen size in patients with myelofibrosis (MF). We retrospectively evaluated efficacy and tolerability of ruxolitinib in a cohort of unselected MF patients treated in routine clinical practice. One hundred and two patients who began ruxolitinib therapy were identified in 13 participating centers. Ninety three of the patients receiving ruxolitinib for at least 3 months were evaluated for treatment efficacy and toxicity. Median age at ruxolitinib initiation was 67 years. Indications for treatment were constitutional symptoms (15%), symptomatic splenomegaly (6%) or both (76%). Two patients received ruxolitinib for other indications. The median initial ruxolitinib dose was 30mg/day. Median duration of therapy was 11 months. Eighty two patients (88.2%) responded to therapy, 76 (84.4%) patients had improvement in constitutional symptoms and 60 patients (70.6%) had reduction in spleen length. While on ruxolitinib, 30% of patients had grade 3-4 anemia and 12.9% of patients had grade 3-4 thrombocytopenia. Thirteen patients (14%) discontinued therapy. This analysis of a cohort of MF patients treated with ruxolitinib in routine clinical practice demonstrates the efficacy and tolerability of this drug outside of a highly monitored clinical trial setting. PMID- 26364798 TI - Azacitidine in the treatment of older patients affected by acute myeloid leukemia: A report by the Rete Ematologica Pugliese (REP). AB - The optimal treatment of older patients (>65 years) with acute myeloid leukemia (AML) remains challenging in daily clinical practice; a choice has to be made between intensive chemotherapy and best supportive care. To guide physicians, several prognostic factors have been identified and risk scores developed. Recently, the DNA methyltransferase inhibitor azacitidine has become available for use in MDS and AML patients with up to 30% bone marrow blasts. However, limited data are available on the outcome of older unfit AML patients, regardless of their bone marrow blast count. We retrospectively analyzed the outcome of 90 newly diagnosed older unfit AML patients in 9 Institutions from the Apulia Region (REP). Responder patients (evaluation performed after 4 cycles of treatment even in cases of primary failure) showed a better overall survival than non responders (23 vs 6 months, p<.001). ECOG PS>=2 seems to be correlated with OS in multivariate analysis, while neither primary treatment failure (documented after 2 cycles) nor bone marrow blast count were correlated with a worse overall survival either at univariate (22 vs 29 months, p=.ns; 16 vs 19 months, p=.ns) or multivariate analysis. Overall, the results of our retrospective analysis seem to confirm the efficacy of AZA treatment for this unfit AML patients setting, in terms of both CR and OS, regardless of the bone marrow blasts count, while primary treatment failure should not lead to a discontinuation of treatment. PMID- 26364799 TI - Present Insights on Cardiomyopathy in Diabetic Patients. AB - The pathogenesis of diabetic cardiomyopathy (DCM) is partially understood and is likely to be multifactorial, involving metabolic disturbances, hypertension and cardiovascular autonomic neuropathy (CAN). Therefore, an important need remains to further delineate the basic mechanisms of diabetic cardiomyopathy and to apply them to daily clinical practice. We attempt to detail some of these underlying mechanisms, focusing in the clinical features and management. The novelty of this review is the role of CAN and reduction of blood pressure descent during sleep in the development of DCM. Evidence has suggested that CAN might precede left ventricular hypertrophy and diastolic dysfunction in normotensive patients with type 2 diabetes, serving as an early marker for the evaluation of preclinical cardiac abnormalities. Additionally, a prospective study demonstrated that an elevation of nocturnal systolic blood pressure and a loss of nocturnal blood pressure fall might precede the onset of abnormal albuminuria and cardiovascular events in hypertensive normoalbuminuric patients with type 2 diabetes. Therefore, existing microalbuminuria could imply the presence of myocardium abnormalities. Considering that DCM could be asymptomatic for a long period and progress to irreversible cardiac damage, early recognition and treatment of the preclinical cardiac abnormalities are essential to avoid severe cardiovascular outcomes. In this sense, we recommend that all type 2 diabetic patients, especially those with microalbuminuria, should be regularly submitted to CAN tests, Ambulatory Blood Pressure Monitoring and echocardiography, and treated for any abnormalities in these tests in the attempt of reducing cardiovascular morbidity and mortality. PMID- 26364801 TI - PI3K isoform-selective inhibitors: next-generation targeted cancer therapies. AB - The pivotal roles of phosphatidylinositol 3-kinases (PI3Ks) in human cancers have inspired active development of small molecules to inhibit these lipid kinases. However, the first-generation pan-PI3K and dual-PI3K/mTOR inhibitors have encountered problems in clinical trials, with limited efficacies as a monotherapeutic agent as well as a relatively high rate of side effects. It is increasingly recognized that different PI3K isoforms play non-redundant roles in particular tumor types, which has prompted the development of isoform-selective inhibitors for pre-selected patients with the aim for improving efficacy while decreasing undesirable side effects. The success of PI3K isoform-selective inhibitors is represented by CAL101 (Idelalisib), a first-in-class PI3Kdelta selective small-molecule inhibitor that has been approved by the FDA for the treatment of chronic lymphocytic leukemia, indolent B-cell non-Hodgkin's lymphoma and relapsed small lymphocytic lymphoma. Inhibitors targeting other PI3K isoforms are also being extensively developed. This review focuses on the recent progress in development of PI3K isoform-selective inhibitors for cancer therapy. A deeper understanding of the action modes of novel PI3K isoform-selective inhibitors will provide valuable information to further validate the concept of targeting specific PI3K isoforms, while the identification of biomarkers to stratify patients who are likely to benefit from the therapy will be essential for the success of these agents. PMID- 26364800 TI - Novel endogenous angiogenesis inhibitors and their therapeutic potential. AB - Angiogenesis, the formation of new blood vessels from the pre-existing vasculature is essential for embryonic development and tissue homeostasis. It also plays critical roles in diseases such as cancer and retinopathy. A delicate balance between pro- and anti-angiogenic factors ensures normal physiological homeostasis. Endogenous angiogenesis inhibitors are proteins or protein fragments that are formed in the body and have the ability to limit angiogenesis. Many endogenous angiogenesis inhibitors have been discovered, and the list continues to grow. Endogenous protein/peptide inhibitors are relatively less toxic, better tolerated and have a lower risk of drug resistance, which makes them attractive as drug candidates. In this review, we highlight ten novel endogenous protein angiogenesis inhibitors discovered within the last five years, including ISM1, FKBPL, CHIP, ARHGAP18, MMRN2, SOCS3, TAp73, ZNF24, GPR56 and JWA. Although some of these proteins have been well characterized for other biological functions, we focus on their new and specific roles in angiogenesis inhibition and discuss their potential for therapeutic application. PMID- 26364803 TI - A cone beam computed tomography (CBCT) study of buccal plate thickness of the maxillary and mandibular posterior dentition. AB - BACKGROUND: Buccal plate thickness is of clinical importance in treatment planning for implants. The purpose of this study was to evaluate the buccal plate thickness in posterior dentate areas of both the maxilla and mandible using cone beam computed tomography in order to estimate the approximate distributions of this anatomic variable. METHODS: Two hundred and sixty-five subjects were included for a total of nine hundred and thirty-four roots assessed by cone beam computed tomography. CBCT scans were taken and evaluated at the ideal buccolingual cross-sections of each root at 1 mm, 3 mm, and 5 mm apical to the alveolar crest to measure buccal plate thickness. Data are reported by geometric means and 95% confidence intervals. RESULTS: Both arches demonstrated increasing buccal plate thickness from anterior to posterior. Maxillary teeth had a significant decrease in thickness from coronal to apical along the tooth root (P < 0.001), except at second molars. The first premolar and mesial root of the first molar were significantly thinner than all other roots in the maxilla. Conversely, the mandible demonstrated a significant increase in buccal plate thickness from coronal to apical (P < 0.001). The premolars were significantly thinner than all other roots. Age and sex were found to have limited impact on buccal plate thickness in both arches. CONCLUSIONS: Buccal plate thickness is highly dependent upon the arch position, tooth location, and measurement point, but age and sex have limited impact. PMID- 26364802 TI - Parkin represses 6-hydroxydopamine-induced apoptosis via stabilizing scaffold protein p62 in PC12 cells. AB - AIM: Parkin has been shown to exert protective effects against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in different models of Parkinson disease. In the present study we investigated the molecular mechanisms underlying the neuroprotective action of parkin in vitro. METHODS: HEK293, HeLa and PC12 cells were transfected with parkin, parkin mutants, p62 or si-p62. Protein expression and ubiquitination were assessed using immunoblot analysis. Immunoprecipitation assay was performed to identify the interaction between parkin and scaffold protein p62. PC12 and SH-SY5Y cells were treated with 6-OHDA (200 MUmol/L), and cell apoptosis was detected using PI and Hoechst staining. RESULTS: In HEK293 cells co-transfected with parkin and p62, parkin was co-immunoprecipitated with p62, and parkin overexpression increased p62 protein levels. In parkin-deficient HeLa cells, transfection with wild-type pakin, but not with ligase activity deficient pakin mutants, significantly increased p62 levels, suggesting that parkin stabilized p62 through its E3 ligase activity. Transfection with parkin or p62 significantly repressed ERK1/2 phosphorylation in HeLa cells, but transfection with parkin did not repress ERK1/2 phosphorylation in p62-knockdown HeLa cells, suggesting that p62 was involved in parkin-induced inhibition on ERK1/2 phosphorylation. Overexpression of parkin or p62 significantly repressed 6 OHDA-induced ERK1/2 phosphorylation in PC12 cells, and parkin overexpression inhibited 6-OHDA-induced apoptosis in PC12 and SH-SY5Y cells. CONCLUSION: Parkin protects PC12 cells against 6-OHDA-induced apoptosis via ubiquitinating and stabilizing scaffold protein p62, and repressing ERK1/2 activation. PMID- 26364804 TI - Interaction of human serum albumin with novel imidazole derivatives studied by spectroscopy and molecular docking. AB - This study was a detailed characterization of the interaction of a series of imidazole derivatives with a model transport protein, human serum albumin (HSA). Fluorescence and time-resolved fluorescence results showed the existence of a static quenching mode for the HSA-imidazole derivative interaction. The binding constant at 296 K was in the order of 10(4) M(-1), showing high affinity between the imidazole derivatives and HSA. A site marker competition study combined with molecular docking revealed that the imidazole derivatives bound to subdomain IIA of HSA (Sudlow's site I). Furthermore, the results of synchronous, 3D, Fourier transform infrared, circular dichroism and UV-vis spectroscopy demonstrated that the secondary structure of HSA was altered in the presence of the imidazole derivatives. The specific binding distance, r, between the donor and acceptor was obtained according to fluorescence resonance energy transfer. PMID- 26364805 TI - Vagus Nerve and Vagus Nerve Stimulation, a Comprehensive Review: Part III. AB - Vagus nerve stimulation (VNS) is currently undergoing multiple trials to explore its potential for various clinical disorders. To date, VNS has been approved for the treatment of refractory epilepsy and depression. It exerts antiepileptic or antiepileptogenic effect possibly through neuromodulation of certain monoamine pathways. Beyond epilepsy, VNS is also under investigation for the treatment of inflammation, asthma, and pain. VNS influences the production of inflammatory cytokines to dampen the inflammatory response. It triggers the systemic release of catecholamines that alleviates the asthma attack. VNS induces antinociception by modulating multiple pain-associated structures in the brain and spinal cord affecting peripheral/central nociception, opioid response, inflammation process, autonomic activity, and pain-related behavior. Progression in VNS clinical efficacy over time suggests an underlying disease-modifying neuromodulation, which is an emerging field in neurology. With multiple potential clinical applications, further development of VNS is encouraging. PMID- 26364806 TI - Manipulation of the phenotypic appearance of individuals in groups of laying hens: effects on stress and immune-related variables. AB - This study evaluated whether phenotypic appearance (PA) alteration during two developmental phases in laying hens, reared in two different group sizes, affects stress and immune responses. After hatching, 750 chicks were randomly assigned to 30 pens at a group size of either 10 or 40 birds. Then, the appearance of 0, 30, 50, 70 or 100% of the chicks in each pen was altered by blackdyeing their head feathers (marked); remaining chicks were unmarked. At 32 weeks, basal and postacute stress plasma corticosterone concentration, leukocyte counts, phytohemagglutinin-p lymphoproliferative and primary antibody responses were measured in six birds/pen. Analysis of variances (ANOVAs) showed no differences among treatment combinations. In a second phase, birds within initially homogeneous pens were sequentially either marked or had dye bleached to alter PA of 70% of hens in each flock (= group in a pen). Hens within initially heterogeneous pens remained unaltered as controls. The above variables were remeasured. Hens in phenotypically manipulated pens showed modified leukocyte counts compared to hens in control pens, indicating a chronic stress reaction in all penmates (whether individual PA was altered or not). Social isolation increased plasma corticosterone concentration. However, within groups of n = 40, phenotypically unaltered hens had lower responses than their altered penmate counterparts, suggesting that remaining in a stable PA group aids better coping with challenges. Although all hens in manipulated pens showed modified leukocyte counts, their antibody and lymphoproliferative responses did not differ from controls suggesting that all groupmates were able to immunologically cope with the challenges presented, within the timeframe evaluated. PMID- 26364808 TI - Clinical outcomes of definitive chemoradiation followed by intracavitary pulsed dose rate image-guided adaptive brachytherapy in locally advanced cervical cancer. AB - OBJECTIVE: To report the outcomes and late toxicities of patients with locally advanced cervical cancer treated with concomitant chemoradiation (CRT) followed by intracavitary image-guided adaptive brachytherapy (IGABT). METHODS: Data from consecutive patients with histologically proven stage IB-IVA cervical cancer treated with curative intent in a single institution were analyzed. After pelvic +/- para-aortic external-beam radiation therapy, they received pulsed-dose rate IGABT following GEC-ESTRO recommendations. RESULTS: Two hundred and twenty-five patients were enrolled. Sixty-five percent were stage>=IIB according to FIGO classification. Ninety-five percent received CRT. Mean D90 to HR and IR-CTV were 80.4+/-10.3Gy and 67.7+/-6.1Gy. After a median follow-up of 38.8months, 3-year local control and overall survival rates were 86.4% and 76.1%, respectively. A trend for a detrimental effect of tumor stage on local control rates was observed with 3-year local control rates of 100% for stages IB1 and IIA, 90.5 for IB2, 85.8% for IIB, 50% for IIIA, 77.1 for IIIB, and 66.7% for IVA tumors (p=0.06). Local control rates at 3years were 95.6% in the group of patients with D90 of HR CTV>=85Gy, 88.8% in those with D90 between 80 and 85Gy, and 80% when D90<80Gy (p=0.018). Eighteen severe late gastrointestinal and urinary effects affecting 14 patients were reported corresponding with a crude incidence of 6.6%. CONCLUSIONS: CRT followed by IGABT provides high local control rates with limited toxicity. Reaching high doses is mandatory to achieve local control and interstitial brachytherapy is necessary in advanced diseases. PMID- 26364810 TI - Controllable Nitrogen Doping of High-Surface-Area Microporous Carbons Synthesized from an Organic-Inorganic Sol-Gel Approach for Li-S Cathodes. AB - High-surface-area microporous carbons with controllable nitrogen doping were prepared via a novel organic-inorganic sol-gel approach, using phenolic resol and hexamethoxymethyl melamine (HMMM) as carbon precursors, and partially hydrolyzed tetraethoxysilane as silica template. The pore structures of microporous carbons were completely replicated from a thin silica framework and could be tailored greatly by changing the organic/inorganic ratio. The nitrogen atoms doped into the carbon framework were issued from high-nitrogen-content HMMM precursors, and the nitrogen content could be adjusted in a wide range by changing the phenolic resol/HMMM ratio. Moreover, the porous structure and nitrogen content could be simultaneously controlled, allowing the preparation of a series of microporous carbons with almost the same microstructures (BET surface areas of ca.1900 m(2).g(-1)and pore volumes of ca. 1.2 cm(3).g(-1), and the same pore size distributions) but with different nitrogen contents (0-12 wt %). These results provided a general method to synthesize nitrogen-doped microporous carbons and allowed these materials to serve as a model system to illustrate the role of nitrogen content on the performance of the carbons. When used as the supports for sulfur cathodes, only an appropriate nitrogen content of ca. 6.3 wt % was found to effectively improve sulfur utilization and cycle life of the sulfur cathodes. The resulting sulfur cathodes could deliver an outstanding reversible discharge capacity of 1054 mAh.g(-1) at 0.5 C after 100 cycles. PMID- 26364809 TI - Assessing the risk of ovarian malignancy algorithm for the conservative management of women with a pelvic mass. AB - OBJECTIVE: To evaluate the use of as an aid in the identification of women who can safely undergo conservative, non-surgical management. METHODS: All patients referred to the Program in Women's Oncology for surgery with a pelvic mass are evaluated at a prospective multidisciplinary tumor board (TB) where ROMA and imaging are used for management recommendations. This study evaluated women presented to TB with a pelvic mass between 2009 and 2013 who had either surgical or conservative management. RESULTS: Of the 498 patients assessed, 392 (79%) had benign disease, 22 (4%) had LMP tumors, 28 (6%) had stage I-II epithelial ovarian cancer (EOC), 36 (7%) had stage III-IV EOC and 20 (4%) had non-EOC. Using clinical assessment in conjunction with ROMA, the TB recommended observation in 188 (37.8%) women. All patients diagnosed with an invasive malignancy were recommended for surgery by the TB. In the 315 patients managed surgically, 212 were found to have benign disease and 84 women were diagnosed with an invasive malignancy. The sensitivity for the initial TB recommendations using ROMA in conjunction with clinical judgment for detecting malignancy was 100% with a specificity of 47.7% and a NPV of 100%. When including low malignant potential tumors the sensitivity was 99.1%. For stage I-IV EOC ROMA alone had a sensitivity of 95.3%. CONCLUSIONS: ROMA in conjunction with clinical assessment can safely identify women for conservative management. PMID- 26364811 TI - Tailoring graphene oxide assemblies by pinning on the contact line of a dissolving microdroplet. AB - The controlled dissolution of microdroplets on a supporting substrate is an effective approach that can be used to tune the assembled microstructure of basic units suspended within the droplet. In this work, we studied the self-assembly of two-dimensional graphene oxide (GO) nanosheets driven by the dissolution of a microdroplet situated at the interface between a solid substrate and the surrounding liquid phase. We found that although uniform microstructures form at the liquid-liquid interface of the droplets, the contact between the droplet and the substrate can give rise to a variety of different morphologies near the base of the droplet. In particular, pinning effects at the boundary of the dissolving droplet on the substrate lead to non-spherical GO assemblies. The results in this work demonstrate the possibility that tailored three-dimensional architectures of nanosheets assembled in a dissolving droplet may be achieved through control of the wetting properties of the droplet on the supporting substrate. PMID- 26364812 TI - Involvement of oxidative stress and mitochondrial/lysosomal cross-talk in olanzapine cytotoxicity in freshly isolated rat hepatocytes. AB - 1. Olanzapine (OLZ) is a widely used atypical antipsychotic agent for the treatment of schizophrenia and other disorders. Serious hepatotoxicity and elevated liver enzymes have been reported in patients receiving OLZ. However, the cellular and molecular mechanisms of the OLZ hepatotoxicity are unknown. 2. In this study, the cytotoxic effect of OLZ on freshly isolated rat hepatocytes was assessed. Our results showed that the cytotoxicity of OLZ in hepatocytes is mediated by overproduction of reactive oxygen species (ROS), mitochondrial potential collapse, lysosomal membrane leakiness, GSH depletion and lipid peroxidation preceding cell lysis. All the aforementioned OLZ-induced cellular events were significantly (p < 0.05) prevented by ROS scavengers, antioxidants, endocytosis inhibitors and adenosine triphosphate generators. Also, the present results demonstrated that CYP450 is involved in OLZ-induced oxidative stress and cytotoxicity mechanism. 3. It is concluded that OLZ hepatotoxicity is associated with both mitochondrial/lysosomal involvement following the initiation of oxidative stress in hepatocytes. PMID- 26364813 TI - [Quality or quantity of life?]. PMID- 26364814 TI - [Supporting caregivers]. PMID- 26364815 TI - [Caregivers of people with neurodegenerative diseases: from help to delegation]. AB - Being a caregiver is difficult, even more so when it comes to helping people with a neurodegenerative disease. These caregivers, either family members or close friends, are confronted with an unexpected delegation which can prove to be highly complex as the pitfalls can indeed be significant. Moreover, the support the caregivers can provide depends on the support they can get for themselves. PMID- 26364816 TI - [Alzheimer's disease, caregiving and frailty]. AB - Caring for a person with Alzheimer's disease often sees the elderly carer at risk of succumbing to frailty. The chronic stress which comes with this caregiving can lead to physical and emotional exhaustion, for which the physiological reserves of the ageing person may be insufficient. The concept of frailty may help to improve the understanding of this vulnerability. PMID- 26364817 TI - [Family caregivers and their support at home]. AB - Home support for carers is a cross-cutting theme running through all the areas of focus of the strategy for the integration of care and assistance services. Thanks to this strategy a health care territory has visibility, legibility and accessibility to the respite care and assistance available to family carers provided by local professionals, notably by those in charge of complex situations, the case managers. PMID- 26364818 TI - [In-home respite for the families of Alzheimer's patients]. AB - An innovative and unique model of respite and support at home for people with Alzheimer's and their carers has been created. The quality of the service provided is based on the principle of home assistance, 24 hours a day and for several consecutive days, provided by a single specialised care assistant. PMID- 26364819 TI - [A geriatrics unit with a 24 hour visiting policy]. AB - As hospitals' visiting times are extended, patients' families and friends are granted an ever more important place. The nursing team of an acute geriatrics unit open 24/7 examined the place and the role of patients' families and friends and their involvement in care. PMID- 26364820 TI - [Empathy fatigue and psychiatric care of the elderly]. AB - Empathy is one of the qualities which enable caregivers to develop high quality care. The circumstances of professional practice such as pressure and lack of time can see this quality pushed to one side. The risk of burnout is all the greater as empathy alone does not protect caregivers from submitting themselves to their hierarchy. Compassion, on the other hand, enables caregivers to actively take on their responsibilities. PMID- 26364821 TI - [Pleasure and aging in the elderly]. AB - A survey carried out of people aged 65 and over aimed to provide a clearer picture of the older population's relationship with pleasure. How do they feel as they age? Do they still find pleasure in things? In what ways? If there a certain self-censorship among the older population with regard to the subject? Or, on the contrary, do they make the most out of life without any complexes or limits? A sample of people aged between 15 and 64 were also surveyed for their opinion on the following questions: do they feel that older people still find pleasure in things? How do senior citizens enjoy themselves today? PMID- 26364822 TI - [Generalized pruritus]. PMID- 26364823 TI - [Pneumonia in the elderly]. PMID- 26364825 TI - Nursing Students' Perceptions of Their Own Caring Behaviors: A Multicountry Study. AB - PURPOSE: The aim of this study was to identify perceptions of caring behaviors in student nurses from four countries. METHODS: This study employed a descriptive, comparative survey design. Four hundred sixty-seven students were recruited from four countries (Nigeria, India, Greece, and the Philippines) to participate in the study during the months of September 2013 to January 2014. Data were collected using the Caring Behavior Inventory. FINDINGS: The highest ranked subscale was "assurance of human presence" (4.827 +/- 0.927), while "positive connectedness" (4.610 +/- 0.949) was the lowest ranked subscale. There were no statistically significant correlations between the Caring Behavior Inventory scale and gender (F = 0.215, p = .643), educational level (F = 0.396, p = .529), and family structure of students (F = 0.680, p = .410), except for age (F = 9.380, p = .002, eta2 = 0.141) and the country of origin (F = 5.772, p = .001, eta2 = 0.036). CONCLUSION: Students from four countries possess positive caring behaviors, specifically on physically based caring interventions, while there is a need to emphasize expressive caring behaviors during nursing education and training. IMPLICATION FOR NURSING PRACTICE: Caring interventions should be carried out in order to help students build or enhance their caring behaviors that can be adapted to clinical situations. PMID- 26364824 TI - Medial olivocochlear efferent reflex inhibition of human cochlear nerve responses. AB - Inhibition of cochlear amplifier gain by the medial olivocochlear (MOC) efferent system has several putative roles: aiding listening in noise, protection against damage from acoustic overexposure, and slowing age-induced hearing loss. The human MOC reflex has been studied almost exclusively by measuring changes in otoacoustic emissions. However, to help understand how the MOC system influences what we hear, it is important to have measurements of the MOC effect on the total output of the organ of Corti, i.e., on cochlear nerve responses that couple sounds to the brain. In this work we measured the inhibition produced by the MOC reflex on the amplitude of cochlear nerve compound action potentials (CAPs) in response to moderate level (52-60 dB peSPL) clicks from five, young, normal hearing, awake, alert, human adults. MOC activity was elicited by 65 dB SPL, contralateral broadband noise (CAS). Using tympanic membrane electrodes, approximately 10 h of data collection were needed from each subject to yield reliable measurements of the MOC reflex inhibition on CAP amplitudes from one click level. The CAS produced a 16% reduction of CAP amplitude, equivalent to a 1.98 dB effective attenuation (averaged over five subjects). Based on previous reports of efferent effects as functions of level and frequency, it is possible that much larger effective attenuations would be observed at lower sound levels or with clicks of higher frequency content. For a preliminary comparison, we also measured MOC reflex inhibition of DPOAEs evoked from the same ears with f2's near 4 kHz. The resulting effective attenuations on DPOAEs were, on average, less than half the effective attenuations on CAPs. PMID- 26364826 TI - Selective internal radiation therapy for liver malignancies. AB - BACKGROUND: Selective internal radiation therapy (SIRT) is a non-ablative technique for the treatment of liver primaries and metastases, with the intention of reducing tumour bulk. This study aimed to determine optimal patient selection, and elucidate its role as a downsizing modality. METHODS: Data were collected retrospectively on patients who underwent SIRT between 2011 and 2014. The procedure was performed percutaneously by an expert radiologist. Response was analysed in two categories, based on radiological (CT/MRI according to Response Evaluation Criteria In Solid Tumours (RECIST)) and biological (alpha-fetoprotein, carcinoembryonic antigen, carbohydrate antigen 19-9, chromogranin A) parameters. RESULTS: Forty-four patients were included. Liver metastases from colorectal cancer (22 patients) and hepatocellular carcinoma (HCC) (9) were the most common pathologies. Radiological response data were collected from 31 patients. A reduction in sum of diameters (SOD) was observed in patients with HCC (median 24.1 (95 per cent c.i. -43.4 to -3.8) per cent) and neuroendocrine tumours (-30.0 (-45.6 to -7.7) per cent), whereas a slight increase in SOD was seen in patients with colorectal cancer (4.9 (-10.6 to 55.3) per cent). Biological response was assessed in 17 patients, with a reduction in 12, a mixed response in two and no improvement in three. Six- and 12-month overall survival rates were 71 and 41 per cent respectively. There was no difference in overall survival between the RECIST response groups (median survival 375, 290 and 214 days for patients with a partial response, stable disease and progressive disease respectively; P = 0.130), or according to primary pathology (P = 0.063). Seven patients underwent liver resection with variable responses after SIRT. CONCLUSION: SIRT may be used to downsize tumours and may be used as a bridge to surgery in patients with tumours deemed borderline for resection. PMID- 26364827 TI - Effects of water states on steam explosion of lignocellulosic biomass. AB - The work aimed to identify the complexity and roles of water states in steam explosion process of corn stalk to enhance the treatment efficiency. Results showed that two main water states with different mobility existed in corn stalk and influenced steam explosion treatment. By correlating dynamic water states data to feedstock mechanical properties and treatment process characteristics, the bound water being the excellent plasticizer that reduced the mechanical strength of fibers by over 30%, was conducive to treatment; while, the free water presenting buffering effects in treatment by hindering heat transfer which was reflected by the increase of temperature rising time by 1.29 folds and steam consumption by 2.18 folds, was not conducive. The distinguished point of these two waters was fiber saturated point. By considering treatment efficacy and energy consumption, the significance of fiber saturated point was highlighted as the optimal water states for steam explosion of corn stalk. PMID- 26364828 TI - Effect of phenolic compounds from pretreated sugarcane bagasse on cellulolytic and hemicellulolytic activities. AB - This work shows both cellulases and hemicellulases are inhibited and deactivated by water-soluble and acetone extracted phenolics from sugarcane bagasse pretreated at 10% (w/v) for 30 min in liquid hot water at 180 or 200 degrees C. The dissolved phenolics in vacuum filtrate increased from 1.4 to 2.4 g/L as temperature increased from 180 to 200 degrees C. The suppression of cellulose and hemicellulose hydrolysis by phenolics is dominated by deactivation of the beta glucosidase or beta-xylosidase components of cellulase and hemicellulase enzyme by acetone extract at 0.2-0.65 mg phenolics/mg enzyme protein and deactivation of cellulases and hemicellulases by the water soluble components in vacuum filtrate at 0.05-2mg/mg. Inhibition was a function of the type of enzyme and the manner in which the phenolics were extracted from the bagasse. PMID- 26364829 TI - Removing Bacillus subtilis from fermentation broth using alumina nanoparticles. AB - In this study, an efficient separation technology using Al2O3 nanoparticles (NPs) was developed for removing Bacillus subtilis from fermentation broth. The dosage of alumina nanoparticles used for separating B. subtilis increased during the culture process and remained stable in the stationary phase of the culture process. The pH of the culture-broth was also investigated for its effects on flocculation efficiency, and showed an acidic pH could enhance the flocculation efficiency. The attachment mechanisms of Al2O3 NPs to the B. subtilis surface were investigated, and the zeta potential analysis showed that Al2O3 NPs could attach to B. subtilis via electrostatic attachment. Finally, the metabolite content and the antibacterial effect of the fermentation supernatants were detected and did not significantly differ between alumina nanoparticle separation and centrifugation separation. Together, these results indicate a great potential for a highly efficient and economical method for removing B. subtilis from fermentation broth using alumina nanoparticles. PMID- 26364830 TI - PET/CT "Virtual" Special Issue. PMID- 26364831 TI - Unmet demand for training among mature age Australians: Prevalence, differentials and perceived causes. AB - AIM: To explore the prevalence of unmet demand for training by mature age Australians and to identify the main barriers to accessing training. METHODS: A total of 3007 Australians aged 45-74 years were surveyed using Computer Assisted Telephone Interviewing. The sample frame was randomly selected and stratified based on the capital city and the rest of the state, and data were weighted to be nationally representative. RESULTS: Over one-third (37%) of respondents who had worked in the past five years reported wanting to attend some form of training but were unable to; these were most likely women and those aged 45-54 year. Commonly cited reasons for not being able to attend training included not being able to fit it in with work commitments, affordability and employer reluctance. CONCLUSION: Reduction of these barriers to workplace training can improve mature age people's ability to remain engaged in the workforce. PMID- 26364832 TI - Continuous versus cyclic oral contraceptives after laparoscopic excision of ovarian endometriomas: a systematic review and metaanalysis. AB - In the lack of evidence consistently supporting the use of continuous vs cyclic oral contraceptives after surgery for endometriosis, we conducted a systematic review and metaanalysis with the objective of comparing a continuous vs a cyclic oral contraceptive schedule administered after surgical excision of ovarian endometriomas. A PubMed, MedLine, and Embase search through December 2014 was conducted, with the use of a combination of key words and text words related to endometrioma, endometriosis, oral contraceptives, oral estroprogestins, laparoscopy, and surgery. Studies directly comparing a continuous vs a cyclic schedule administered after surgical treatment of endometriomas were included, with pain and endometrioma recurrence rates as the primary outcomes. Three reviewers independently assessed methodology and extracted data from selected studies. The primary outcomes were considered pain recurrence (evaluated separately for dysmenorrhea, noncyclic chronic pelvic pain, and dyspareunia) and endometrioma recurrence evaluated at ultrasonography. Dichotomous outcomes from each study were expressed as risk ratio (RR) with a 95% confidence interval (CI). Three randomized clinical trials and 1 prospective controlled cohort study were included, for a total of 557 patients with endometriosis, 343 patients of whom had ovarian endometriomas completing the assigned treatment and follow-up. Lower recurrence rates for dysmenorrhea were obtained with a continuous schedule (RR, 0.24; 95% CI, 0.06-0.91; P = .04). Nonsignificant differences were present for chronic pelvic pain and dyspareunia. A continuous oral contraceptive schedule was associated with a nonsignificant reduction of cyst recurrence rates compared with a cyclic schedule (RR, 0.54; 95% CI, 0.28-1.05; P = .07). A continuous oral contraceptive regimen, as opposed to a cyclic regimen, may be suggested after surgery for endometriomas because of lower dysmenorrhea recurrence rates. Due to the small number and small sample sizes of the included studies, further randomized clinical trials are needed to confirm the findings of the present systematic review. Also, outcomes related to patient satisfaction and quality of life should be addressed. PMID- 26364833 TI - Efficacy of midtrimester short cervix interventions is conditional on intraamniotic inflammation. AB - BACKGROUND: Midtrimester ultrasound is a valuable method for identifying asymptomatic women at risk for spontaneous preterm delivery (PTD). However, response to various treatments (cerclage, progestogen) has been variable in the clinical setting. It remains unclear how other biomarkers may be used to guide intervention strategies. OBJECTIVE: We applied an amniotic fluid inflammatory scoring system to determine if the degree of inflammation is associated with intervention efficacy in patients with midtrimester short cervix. STUDY DESIGN: Women carrying a singleton fetus between 16-24 weeks' gestation with a short cervix (<=25 mm) on transvaginal ultrasound underwent amniocentesis and were assigned to McDonald cerclage, no cerclage, or weekly 17-alpha hydroxyprogesterone caproate (17OHP-C). Our previously described inflammatory risk score (comprised of 14 inflammatory markers) was used to classify patients as high (score >=8) or low (score <8) risk for inflammation. Gestational age at delivery was compared for each intervention and risk score status. Risk of delivering as a function of the remaining gestation was evaluated using modified Cox proportional hazards models with incorporation of methods to account for both left and right truncation bias. RESULTS: Ninety patients were included: 24 were in the nonintervention control group, 51 received cerclage, and 15 received 17OHP C. Inflammation status at time of sampling influenced the efficacy of the treatment (P < .001). Compared to the nonintervention control group, in patients with low inflammation (score < 8), both cerclage (adjusted hazard ratio [HR], 2.86; 95% confidence interval [CI], 1.28-6.37) and 17OHP-C (HR, 3.11; 95% CI, 1.04-9.30) were associated with increased hazard of PTD. In contrast, in patients with high inflammation (score >=8) both cerclage (HR, 0.22; 95% CI, 0.08-0.65) and 17OHP-C (HR, 0.20; 95% CI, 0.05-0.81) were associated with lower hazard of delivering preterm. CONCLUSION: Cerclage placement or administration of 17OHP-C therapy for midtrimester short cervix for PTD prevention appears beneficial only in the subset of patients with high inflammation. Knowledge of the amniotic fluid inflammatory status may aid in guiding the appropriate therapy for women presenting with midtrimester short cervix who are at increased risk of PTD. PMID- 26364834 TI - Emotion Recognition in Blended Facial Expressions in Women with Anorexia Nervosa. AB - People with anorexia nervosa (AN) have difficulties in the social domain, and problems in the ability to recognise emotions in people's faces may contribute to these difficulties. This study aimed to investigate emotion recognition in women with AN and healthy controls (HC), using pictures of faces portraying blended emotions at different levels of ambiguity, which resemble real-life expressions more closely than prototypical expressions used in past studies. Seventy-seven participants (35 AN; 42 HC) completed the emotion recognition task. Results indicated that participants with AN were less accurate than HC recognising expressions of disgust, when shown less ambiguously. There were no differences in the recognition of other emotions. Participants with AN also showed response bias towards anger. These findings suggest a generally preserved ability to recognise emotions in women with AN, with the exception of disgust recognition. They also support previous findings of bias towards anger in AN patients. PMID- 26364835 TI - A newborn tolerated severe hypercapnia during general anesthesia: a case report. AB - INTRODUCTION: Severe hypercapnia is a rare but harmful complication of general anesthesia. We report the case of a newborn who developed severe hypercapnia with unknown reasons during general anesthesia but recovered well. This report will advance our understanding about the causes of severe hypercapnia during anesthesia, the possible compensatory mechanisms and the characteristics of neonatal respiratory physiology and intracellular buffering systems. CASE PRESENTATION: A 21-day-old Chinese baby girl who had an incarcerated hernia received an emergent exploratory operation under general anesthesia. She developed severe hypercapnia during surgery for unclear reasons. Arterial blood gas revealed a PCO2 of 149mmHg. Troubleshooting and relevant measures were taken, but the level of CO2 did not decrease. In spite of the high level of PCO2, the newborn recovered well without any complications. CONCLUSIONS: Neonates are vulnerable to hypercapnia during anesthesia for their characteristic respiratory physiology. Heat and moisture exchange should be used with caution in newborns under general anesthesia as it can increase dead space. Intracellular buffering systems play an important role in tolerating severe hypercapnia. Although this case raised a great challenge to the homeostatic mechanism of the body, measures should be taken to maintain PCO2 values around the clinically acceptable level. PMID- 26364836 TI - Monitoring for Extra-Intestinal Cancers in IBD. AB - Multiple studies have demonstrated an increased risk for extra-intestinal cancers in inflammatory bowel disease (IBD) patients, mainly from treatment modalities. Prominent cancers that are related to IBD treatment include the following: lymphoproliferative disorders associated with thiopurine use, hepatosplenic T cell lymphoma primarily in younger male patients on thiopurines and anti-tumor necrosis factor (TNF) agents, non-melanoma skin cancers in patients treated with thiopurines and anti-TNF agents, and melanomas in patients who are on monotherapy with anti-TNF agents. In addition, women with IBD may have higher rates of cervical dysplasia and cervical cancer. The focus of this review is to provide a comprehensive overview on extra-intestinal cancers in IBD patients and how to monitor for these malignancies. PMID- 26364837 TI - The accuracy of suicide statistics: are true suicide deaths misclassified? AB - PURPOSE: Official suicide statistics often produce an inaccurate view of suicide populations, since some deaths endorsed as being of uncertain manner are in fact suicides; it is common, therefore, in suicide research, to account for these deaths. We aimed to test the hypothesis that non-suicide death categories contain a large potential reservoir of misclassified suicides. METHODS: Data on undetermined intent and ill-defined death causes, and official suicide deaths recorded in the district of Tel Aviv for the years 2005 and 2008 were extracted. Based on supplementary data, cases regarded as probable suicides ("suicide probable") were then compared with official suicides ("suicide verdicts") on a number of socio-demographic variables, and also in relation to the mechanism of death. RESULTS: Suicide rates were 42 % higher than those officially reported after accounting for 75 probable suicides (erroneously certified under other cause-of-death categories). Both death classifications ("suicide probable" and "suicide verdicts") had many similarities, significantly differing only with respect to method used. Logistic regression confirmed that the most powerful discriminator was whether the mechanism of death was considered "less active" or "more active" (p < 0.001). Indeed, deaths among the less active group were 4.9 times as likely to be classified as "suicide probable" than were deaths among the more active group. CONCLUSIONS: Caution is needed when interpreting local area data on suicide rates, and undetermined and ill-defined deaths should be included in suicide research after excluding cases unlikely to be suicides. Improving suicide case ascertainment, using multiple sources of information, and uniform reporting practices, is advised. PMID- 26364838 TI - Disparities in access to effective treatment for infertility in the United States: an Ethics Committee opinion. AB - In the United States, economic, racial, ethnic, geographic, and other disparities exist in access to fertility treatment and in treatment outcomes. This opinion examines the factors that contribute to these disparities and proposes actions to address them. PMID- 26364839 TI - New methods to improve the safety assessment of cryopreserved ovarian tissue for fertility preservation in breast cancer patients. AB - OBJECTIVE: To develop a novel molecular panel of markers to detect breast cancer (BC) disseminated malignant cells in ovarian tissue, and to improve the safety of ovarian tissue transplantation. DESIGN: Experimental study. SETTING: University hospital. PATIENT(S): Ten ovarian biopsies from healthy patients, 13 biopsies with diagnosed BC metastasis, and 4 biopsies from primary BC tumor for designing a diagnostic panel of BC cell contamination; 60 ovarian biopsies from BC patients undergoing fertility preservation for validating the panel. ANIMAL(S): Female nude mice. INTERVENTION(S): A novel panel for BC malignant cell detection by reverse-transcription polymerase chain reaction (RT-PCR), inmmunohistochemical analysis, in vitro invasion assay and xenotransplantation assayed in ovarian tissue from BC patients. MAIN OUTCOME MEASURE(S): Expression of GCDFP15, MGB1, SBEM, MUC1, WT-1, and NY-BR-01, selected as markers, assessed by quantitative RT PCR in samples with confirmed BC metastasis. The most sensitive markers were confirmed by immunohistochemistry, and tested in vitro and in vivo. RESULT(S): GCDFP15, MGB1, and SBEM were the most sensitive and specific markers to detect BC metastatic cells when at least one was expressed by quantitative RT-PCR. The panel was validated in 60 patients and confirmed in an in vitro invasion assay, where no invasive cells were observed. Samples negative for BC cells cannot develop disease when xenografted. CONCLUSION(S): GCDFP15, MGB1, and SBEM were the most sensitive molecules to create a diagnostic panel for BC malignant cell contamination, which may make ovarian tissue cryopreservation and transplantation a safe technique for fertility preservation in BC patients. PMID- 26364840 TI - Are pregnancy planning and timing associated with preterm or small for gestational age births? AB - OBJECTIVE: To investigate whether unplanned or poorly timed pregnancies (self reported at enrollment) are associated with preterm or small for gestational age births. DESIGN: Prospective cohort study. SETTING: Not applicable. PATIENT(S): Two thousand six hundred fifty-four pregnant women <18 weeks estimated gestational age with a singleton pregnancy. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Preterm and small for gestational age births. RESULT(S): In adjusted analyses, pregnancy planning was not statistically significantly associated with preterm (odds ratio [OR] 1.18; 95% confidence interval [CI], 0.85-1.65) or small for gestational age birth (OR 1.17; 95% CI, 0.69-1.97). Similarly, poorly timed pregnancies were not statistically significantly associated with preterm (OR 0.85; 95% CI, 0.53-1.38) or small for gestational age birth (OR 0.92; 95% CI, 0.65-1.29). Combining pregnancy planning (yes/no) and timing (yes/no) into a 4 level category showed no statistically significant association with preterm birth or small for gestational age. CONCLUSION(S): In a large cohort with antenatally assessed pregnancy planning and timing, outcome data collected from medical record abstraction, and robust analysis adjusting for multiple confounding factors including maternal demographics, medical conditions, and other risk factors, neither pregnancy planning nor pregnancy timing showed a statistically significant association with preterm or small for gestational age infants. This study improves upon previous analyses that lacked adjustment for confounding and used retrospective self-reporting to assess pregnancy planning and timing, and preterm and small for gestational age births. Findings may differ in higher risk populations with higher prevalence of preterm or small for gestational age births. PMID- 26364841 TI - The hospital outcomes compared between the early and late hypothermia-treated groups in neonates. AB - BACKGROUND AND OBJECTIVE: The incidence of hypoxic ischemic encephalopathy (HIE) in developed countries is estimated to be 1.5 per 1000 live births. The primary aim of this study was to analyze whether earlier hypothermia (<=1 h) improves hospital outcomes in survivors who underwent therapeutic hypothermia (TH) when compared with late TH (>1 h). METHOD: Forty-nine (70%) newborns received TH for 72 h, within 6 h of birth; the remaining 21 received standard care. We divided the TH-treated newborns into early and late groups; early cooling was considered when TH was started <=1 h after birth; late cooling was considered when started >1 h. RESULTS: The early TH group consisted of 20 of 49 (41%) infants; the late TH group consisted of 29 (59%) infants. Apgar score at 1 min and the initial calcium level was significantly lower in the early (<=1 h) TH infants; there were significantly more inborns in the early TH group (p = 0.008). Infants in the late TH group manifested more clinical seizures followed by more abnormal EEG findings, longer ventilator care and longer hospitalization (p = 0.001). TH related complications and mortality were not significantly different between the two groups. CONCLUSIONS: Early TH (<=1 h) had lower Apgar score at 1 min and initial calcium level, but had decreased incidence of clinico-electrical seizures among HIE infants. Also, ventilator support and hospitalization period were longer in the late TH group. PMID- 26364842 TI - Missed low-grade infection in suspected aseptic loosening has no consequences for the survival of total hip arthroplasty. AB - BACKGROUND AND PURPOSE: Aseptic loosening and infection are 2 of the most common causes of revision of hip implants. Antibiotic prophylaxis reduces not only the rate of revision due to infection but also the rate of revision due to aseptic loosening. This suggests under-diagnosis of infections in patients with presumed aseptic loosening and indicates that current diagnostic tools are suboptimal. In a previous multicenter study on 176 patients undergoing revision of a total hip arthroplasty due to presumed aseptic loosening, optimized diagnostics revealed that 4-13% of the patients had a low-grade infection. These infections were not treated as such, and in the current follow-up study the effect on mid- to long term implant survival was investigated. PATIENTS AND METHODS: Patients were sent a 2-part questionnaire. Part A requested information about possible re-revisions of their total hip arthroplasty. Part B consisted of 3 patient-related outcome measure questionnaires (EQ5D, Oxford hip score, and visual analog scale for pain). Additional information was retrieved from the medical records. The group of patients found to have a low-grade infection was compared to those with aseptic loosening. RESULTS: 173 of 176 patients from the original study were included. In the follow-up time between the revision surgery and the current study (mean 7.5 years), 31 patients had died. No statistically significant difference in the number of re-revisions was found between the infection group (2 out of 21) and the aseptic loosening group (13 out of 152); nor was there any significant difference in the time to re-revision. Quality of life, function, and pain were similar between the groups, but only 99 (57%) of the patients returned part B. INTERPRETATION: Under-diagnosis of low-grade infection in conjunction with presumed aseptic revision of total hip arthroplasty may not affect implant survival. PMID- 26364843 TI - Synthesis and discovery of phytofurans: metabolites of alpha-linolenic acid peroxidation. AB - Phytofurans are novel metabolites produced by non-enzymatic peroxidation of alpha linolenic acid. An unprecedented Payne rearrangement-cyclization of a C2 symmetric bis-epoxide permitted construction of the core 3-hydroxy-2,5 disubstituted tetrahydrofuran. LC-MS/MS investigation provided evidence for the presence of phytofurans in nuts and seeds for the first time. PMID- 26364844 TI - miR-221 and miR-222 Simultaneously Target RECK and Regulate Growth and Invasion of Gastric Cancer Cells. AB - BACKGROUND: Although Helicobacter pylori infection is necessary for development of gastric adenocarcinoma (GAC), the underlying mechanism remains poorly defined. This study aimed to explore how miR-221 and miR-222 are dysregulated after H. pylori infection and how these 2 miRNAs are involved in pathological development of gastric cancer. MATERIAL AND METHODS: qRT-PCR analysis was performed to quantify miR-221 and miR-222 expression in patients with H. pylori - induced chronic gastritis, H. pylori-negative healthy controls, and in gastric cancer tissues and the corresponding adjacent normal tissues. Cell models were used to verify the expression profile. Dual luciferase assay was performed to verify putative binding between miR-221 or miR-222 and RECK. A loss-and-gain function study was performed to assess the miR-221/miR-222-RECK axis in gastric cancer cells. RESULTS: H. pylori infection leads to significantly higher miR-221 and miR 222 expression. MiR-221 and miR-222 can bind the same sequence of RECK 3'UTR, thereby modulating its expression. Through simultaneous regulation over RECK, miR 221 and miR-222 can promote gastric cancer cell growth and invasion. CONCLUSIONS: The miR-221/miR-222-RECK axis might be an important path modulating H. pylori infection-related gastric cancer development. PMID- 26364845 TI - Evaluation of antibiotic efficacy against infections caused by planktonic or biofilm cultures of Pseudomonas aeruginosa and Klebsiella pneumoniae in Galleria mellonella. AB - The lack of novel antibiotics for more than a decade has placed increased pressure on existing therapies to combat the emergence of multidrug-resistant (MDR) bacterial pathogens. This study evaluated the Galleria mellonella insect model in determining the efficacy of available antibiotics against planktonic and biofilm infections of MDR Pseudomonas aeruginosa and Klebsiella pneumoniae strains in comparison with in vitro minimum inhibitory concentration (MIC) determination. In general, in vitro analysis agreed with the G. mellonella studies, and susceptibility in Galleria identified different drug resistance mechanisms. However, the carbapenems tested appeared to perform better in vivo than in vitro, with meropenem and imipenem able to clear K. pneumoniae and P. aeruginosa infections with strains that had bla(NDM-1) and bla(VIM) carbapenemases. This study also established an implant model in G. mellonella to allow testing of antibiotic efficacy against biofilm-derived infections. A reduction in antibiotic efficacy of amikacin against K. pneumoniae and P. aeruginosa biofilms was observed compared with a planktonic infection. Ciprofloxacin was found to be less effective at clearing a P. aeruginosa biofilm infection compared with a planktonic infection, but no statistical difference was seen between K. pneumoniae biofilm and planktonic infections treated with this antibiotic (P>0.05). This study provides important information regarding the suitability of Galleria as a model for antibiotic efficacy testing both against planktonic and biofilm-derived MDR infections. PMID- 26364846 TI - Reaction to Dalhoff and Levy: 'Does use of the polyene natamycin as a food preservative jeopardise the clinical efficacy of amphotericin B? A word of concern'. PMID- 26364847 TI - Deletions in a ribosomal protein-coding gene are associated with tigecycline resistance in Enterococcus faecium. AB - Enterococcus faecium is an emerging nosocomial pathogen associated with antibiotic therapy in the hospital environment. Whole-genome sequences were determined for three pairs of related, consecutively collected E. faecium clinical isolates to determine putative mechanisms of resistance to tigecycline. The first isolates (1S, 2S and 3S) in each of the three pairs were sensitive to tigecycline [minimum inhibitory concentration (MIC) of 0.125 mg/L]. Following tigecycline therapy, the second isolate in each pair demonstrated increased resistance to tigecycline. Two isolates (1R and 2R) were resistant (MIC of 8 mg/L) and one isolate (3I) demonstrated reduced susceptibility (MIC of 0.5 mg/L). Mutations distinguishing each pair of sensitive and resistant isolates were determined through alignment to a reference genome and variant detection. In addition, a de novo assembly of each isolate genome was constructed to confirm mutations. A total of 16 mutations in eleven coding sequences were determined. Mutations in the rpsJ gene, which encodes a structural protein forming part of the 30S ribosomal subunit, were detected in each of the pairs. Mutations were in regions proximal to the predicted tigecycline-binding site. Predicted amino acid substitutions were detected in 1R and 3I. The resistant strains were additionally associated with deletions of 15 nucleotides (2R) and 3 nucleotides (1R). This study confirms that amino acid substitutions in rpsJ contribute towards reduced susceptibility to tigecycline and suggests that deletions may be required for tigecycline resistance in E. faecium. PMID- 26364848 TI - More accurate measurement of vancomycin minimum inhibitory concentration indicates poor outcomes in meticillin-resistant Staphylococcus aureus bacteraemia. AB - Meticillin-resistant Staphylococcus aureus (MRSA) is an important pathogen associated with community-acquired and nosocomial infections. The aim of this study was to validate the vancomycin (VAN) minimum inhibitory concentration (MIC) and administration of VAN that may affect the prognosis of patients with MRSA bacteraemia. In total, 140 clinical MRSA strains from blood cultures were collected from January 2009 to December 2013 at a university hospital in Tokyo (Japan). Patient background, their clinical situation and the susceptibility of isolates to anti-MRSA agents in all cases were reviewed, and factors contributing to 30-day mortality were analysed. Susceptibility to anti-MRSA agents was measured by a microdilution susceptibility testing method. The VAN MIC was further evaluated at 0.25 MUg/mL intervals from 0.5 MUg/mL to 2.0 MUg/mL. Multiple logistic regression analysis revealed a 4-fold increase in mortality of patients with a VAN MIC >=1.5 MUg/mL [odds ratio (OR)=3.952, 95% confidence interval (CI) 1.471-10.614; P=0.006]. A one-score increase in the Charlson co morbidity index resulted in a 1.2-fold increase in the risk of death (OR=1.199, 95% CI 1.054-1.364; P=0.006). However, no significant difference was found in the ratio of the VAN 24-h area under the concentration-time curve to MIC between VAN MIC >=1.5 MUg/mL and <1.5 MUg/mL. A significant increase in the MICs of teicoplanin and daptomycin was observed in strains with high VAN MICs. For patients with high VAN MICs, administration of these anti-MRSA antibiotics may have a poor outcome owing to cross-resistance. PMID- 26364849 TI - [The challenge of administering anti-tuberculosis treatment in infants and pre school children. pTBred Magistral Project]. AB - INTRODUCTION: There are no paediatric formulations of anti-tuberculous drugs in Spain, with the only exception being rifampicin. Some paediatricians often prescribe composite formulations (CF), while others prefer to give crushed tablets. Nevertheless, there is no consensus in this regard, or any pharmacokinetic studies validating these procedures. In this situation, the Spanish Network for the Study of Paediatric Tuberculosis (pTBred) has launched the Magistral Project, which has as its first phase aims to analyse the desirability of developing child-friendly pharmaceutical formulations and other aspects regarding the anti-tuberculous drug prescription in children. MATERIAL AND METHODS: A cross-sectional, multicentre, nationwide study was conducted, based on an online questionnaire sent to members of pTBred between February and March 2015. RESULTS: Fifty-four responses from 67 consulted institutions were received. Most of the respondents reported prescribing crushed tablets. A significant number of those surveyed, although being fewer, prescribe CF, for which availability varies widely among institutions. Eighty-three percent replied that it would be essential to have fixed dose combinations of anti-tuberculous drugs, specifically adapted to paediatric doses and administered by CF or tablets. Among the surveyed institutions, differences were found in the management of latent tuberculosis infection, in the use of directly observed therapy, and in the monitoring of adverse events. CONCLUSIONS: Our survey reveals great diversity in anti-tuberculous drug prescription in children, due to the lack of suitable infant formulations, which could have an impact on treatment adherence and outcomes. pTBred intends to develop a pioneering and useful consensus document on the management of anti-tuberculous medication in children. PMID- 26364850 TI - Increased risk of chronic obstructive pulmonary disease among patients with Helicobacter pylori infection: a population-based cohort study. AB - BACKGROUND: Increasing evidence suggests that Helicobacter pylori infection (HPI) may have extragastric manifestations, including the respiratory system. This study investigated the role of HPI in increasing the subsequent risk of chronic obstructive pulmonary disease (COPD) in a nationwide population. METHODS: We conducted this retrospective cohort study using data from the Longitudinal Health Insurance Database, which is derived from the Taiwanese National Health Insurance Research Database. A total of 5941 adults who were newly diagnosed with HPI between 2005 and 2006 were selected. Healthy patients without HPI were selected from the general population and frequency matched as a ratio of 4:1, according to age, sex, and index years. Both cohorts were followed up from the index date to the end of 2011 to measure the incidence of COPD. Cox proportional hazard regression analysis was used to assess the hazard ratio (HR) of COPD between the HPI cohort and non-HPI cohorts. RESULTS: The overall HR of COPD was 1.84 (95% confidence intervals = 1.57-2.17) for the HPI cohort, compared with the non-HPI cohort, after adjusting for age, sex, and comorbidities. Although the incidence of COPD was substantially higher in the elderly participants (age, >= 65 years) than that in younger participants, the highest HR (4.05, 95% confidence intervals = 1.39-11.8) of COPD was observed in the youngest (age, 20-49 years) participants. CONCLUSION: In this study, the patients with HPI exhibited a significantly higher risk of COPD than those without HPI did. PMID- 26364851 TI - Structure of Human B12 Trafficking Protein CblD Reveals Molecular Mimicry and Identifies a New Subfamily of Nitro-FMN Reductases. AB - In mammals, B12 (or cobalamin) is an essential cofactor required by methionine synthase and methylmalonyl-CoA mutase. A complex intracellular pathway supports the assimilation of cobalamin into its active cofactor forms and delivery to its target enzymes. MMADHC (the methylmalonic aciduria and homocystinuria type D protein), commonly referred to as CblD, is a key chaperone involved in intracellular cobalamin trafficking, and mutations in CblD cause methylmalonic aciduria and/or homocystinuria. Herein, we report the first crystal structure of the globular C-terminal domain of human CblD, which is sufficient for its interaction with MMADHC (the methylmalonic aciduria and homocystinuria type C protein), or CblC, and for supporting the cytoplasmic cobalamin trafficking pathway. CblD contains an alpha+beta fold that is structurally reminiscent of the nitro-FMN reductase superfamily. Two of the closest structural relatives of CblD are CblC, a multifunctional enzyme important for cobalamin trafficking, and the activation domain of methionine synthase. CblD, CblC, and the activation domain of methionine synthase share several distinguishing features and, together with two recently described corrinoid-dependent reductive dehalogenases, constitute a new subclass within the nitro-FMN reductase superfamily. We demonstrate that CblD enhances oxidation of cob(II)alamin bound to CblC and that disease-causing mutations in CblD impair the kinetics of this reaction. The striking structural similarity of CblD to CblC, believed to be contiguous in the cobalamin trafficking pathway, suggests the co-option of molecular mimicry as a strategy for achieving its function. PMID- 26364853 TI - Massive thymic hyperplasia in a neonate with Beckwith-Wiedemann syndrome. PMID- 26364852 TI - Cystatin D locates in the nucleus at sites of active transcription and modulates gene and protein expression. AB - Cystatin D is an inhibitor of lysosomal and secreted cysteine proteases. Strikingly, cystatin D has been found to inhibit proliferation, migration, and invasion of colon carcinoma cells indicating tumor suppressor activity that is unrelated to protease inhibition. Here, we demonstrate that a proportion of cystatin D locates within the cell nucleus at specific transcriptionally active chromatin sites. Consistently, transcriptomic analysis show that cystatin D alters gene expression, including that of genes encoding transcription factors such as RUNX1, RUNX2, and MEF2C in HCT116 cells. In concordance with transcriptomic data, quantitative proteomic analysis identified 292 proteins differentially expressed in cystatin D-expressing cells involved in cell adhesion, cytoskeleton, and RNA synthesis and processing. Furthermore, using cytokine arrays we found that cystatin D reduces the secretion of several protumor cytokines such as fibroblast growth factor-4, CX3CL1/fractalkine, neurotrophin 4 oncostatin-M, pulmonary and activation-regulated chemokine/CCL18, and transforming growth factor B3. These results support an unanticipated role of cystatin D in the cell nucleus, controlling the transcription of specific genes involved in crucial cellular functions, which may mediate its protective action in colon cancer. PMID- 26364854 TI - Role of platinum DNA damage-induced transcriptional inhibition in chemotherapy induced neuronal atrophy and peripheral neurotoxicity. AB - Platinum-based anticancer drugs cause peripheral neurotoxicity by damaging sensory neurons within the dorsal root ganglia (DRG), but the mechanisms are incompletely understood. The roles of platinum DNA binding, transcription inhibition and altered cell size were investigated in primary cultures of rat DRG cells. Click chemistry quantitative fluorescence imaging of RNA-incorporated 5 ethynyluridine showed high, but wide ranging, global levels of transcription in individual neurons that correlated with their cell body size. Treatment with platinum drugs reduced neuronal transcription and cell body size to an extent that corresponded to the amount of preceding platinum DNA binding, but without any loss of neuronal cells. The effects of platinum drugs on neuronal transcription and cell body size were inhibited by blocking platinum DNA binding with sodium thiosulfate, and mimicked by treatment with a model transcriptional inhibitor, actinomycin D. In vivo oxaliplatin treatment depleted the total RNA content of DRG tissue concurrently with altering DRG neuronal size. These findings point to a mechanism of chemotherapy-induced peripheral neurotoxicity, whereby platinum DNA damage induces global transcriptional arrest leading in turn to neuronal atrophy. DRG neurons may be particularly vulnerable to this mechanism of toxicity because of their requirements for high basal levels of global transcriptional activity. Findings point to a new stepwise mechanism of chemotherapy-induced peripheral neurotoxicity, whereby platinum DNA damage induces global transcriptional arrest leading in turn to neuronal atrophy. Dorsal root ganglion neurons may be particularly vulnerable to this neurotoxicity because of their high global transcriptional outputs, demonstrated in this study by click chemistry quantitative fluorescence imaging. PMID- 26364855 TI - The metabolic response of marine copepods to environmental warming and ocean acidification in the absence of food. AB - Marine copepods are central to the productivity and biogeochemistry of marine ecosystems. Nevertheless, the direct and indirect effects of climate change on their metabolic functioning remain poorly understood. Here, we use metabolomics, the unbiased study of multiple low molecular weight organic metabolites, to examine how the physiology of Calanus spp. is affected by end-of-century global warming and ocean acidification scenarios. We report that the physiological stresses associated with incubation without food over a 5-day period greatly exceed those caused directly by seawater temperature or pH perturbations. This highlights the need to contextualise the results of climate change experiments by comparison to other, naturally occurring stressors such as food deprivation, which is being exacerbated by global warming. Protein and lipid metabolism were up-regulated in the food-deprived animals, with a novel class of taurine containing lipids and the essential polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid and docosahexaenoic acid, changing significantly over the duration of our experiment. Copepods derive these PUFAs by ingesting diatoms and flagellated microplankton respectively. Climate-driven changes in the productivity, phenology and composition of microplankton communities, and hence the availability of these fatty acids, therefore have the potential to influence the ability of copepods to survive starvation and other environmental stressors. PMID- 26364856 TI - Clinical, epidemiological and treatment failure data among HIV-1 non-B-infected patients in the Spanish AIDS Research Network Cohort. AB - INTRODUCTION: The prevalence of HIV-1 non-B variants is increasing in Spain, showing a higher number of transmitted drug resistance mutations (TDR) since 2002. This study presents the features of non-B-infected patients enrolled in the cohort of antiretroviral treatment (ART) naive HIV-infected patients included in the Research Network on HIV/AIDS (CoRIS). METHODS: The study includes a selected group of HIV-1 non-B-infected subjects from 670 subjects with pol sequences collected from 2004 to 2008 in the CoRIS cohort. Epidemiological-clinical virological data were analyzed since cohort entry until October 2011, considering the presence or absence of treatment failure (TF). RESULTS: Eighty two non-B infected subjects with known HIV-1 variants were selected from 2004 to 2008 in the CoRIS cohort, being mainly female, immigrants, infected by recombinant viruses, and by heterosexual route. They had an intermediate TDR rate (9.4%), a high rate of TF (25.6%), of losses to follow-up (35%), of coinfections (32.9%), and baseline CD4+ counts >=350cells/mm(3) (61.8%). Non-B subjects with TF showed higher rates of heterosexual infection (85.7% vs. 69.5%, p<0.05), tuberculosis (30.8% vs. 9.1%, p=0.10) and hepatitis C (23.8% vs. 13.9%, p=0.34) coinfections and lower rates of syphilis (0% vs. 21.9%, p<0.05), and had more frequently received first-line ART including protease inhibitors (PIs) than patients without TF (70% vs. 30%, p<0.05). Interestingly, infection with non-B variants reduced the risk of TDR to nucleoside reverse transcriptase inhibitors and increased the risk to PIs. CONCLUSION: HIV-1 non-B-infected patients in Spain had a particular epidemiological and clinical profile that should be considered during their clinical management. PMID- 26364857 TI - Trends in nosocomial infections and multidrug-resistant microorganisms in Spanish pediatric intensive care units. AB - INTRODUCTION: Nosocomial infections (NI) are a major healthcare problem. National surveillance systems enable data to be compared and to implement new measures to improve our practice. METHODS: A multicentre, prospective, descriptive and observational study was conducted using the data from surveillance system for nosocomial infections created in 2007 for Spanish pediatric intensive care units. Data were collected for one month, between 01 and 31 March, for every study year (2008-2012). The objective was to report 5-years of NI surveillance data, as well as trends in infections by multidrug resistant organisms in Spanish pediatric intensive care units. RESULTS: A total of 3667 patients were admitted to the units during the study period. There were 90 (2.45%) patients with nosocomial infections. The mean rates during the 5 years study were: central line-associated bloodstream infection, 3.8/1000 central venous catheter-days, Ventilator associated pneumonia 7.5/1000 endotracheal tube-days, and catheter-associated urinary tract infections 4.1/1000 urinary catheter-days. The comparison between the 2008 and 2009 rates for nosocomial infections did not show statistically significant differences. All rates homogeneously decreased from 2009 to 2012: central line-associated bloodstream infection 5.83 (95% CI 2.67-11.07) to 0.49 (95% CI 0.0125-2.76), P=0.0029; ventilator-associated pneumonia 10.44 (95% CI 5.21-18.67) to 4.04 (95% CI 1.48-8.80), P=0.0525; and Catheter-associated urinary tract infections 7.10 (95% CI 3.067-13.999) to 2.56 (95% CI 0.697-6.553), P=0.0817; respectively. The microorganism analysis: 63 of the 99 isolated bacteria (63.6%) were Gram-negative bacteria (36.5% were resistant), 19 (19.2%) Gram-positive bacteria, and 17 (17.2%) were Candida spp. infections. CONCLUSIONS: The local surveillance systems provide information for dealing with nosocomial infections rates. PMID- 26364858 TI - [Bacteremia by Gardnerella vaginalis in a case of complicated urolithiasis]. PMID- 26364859 TI - Urachal carcinoma: a pathologic and clinical study of 46 cases. AB - Urachal carcinoma is a rare tumor that has not been well studied. To determine the pathologic and clinical features of this disease, we retrospectively evaluated 46 cases from our surgical pathology files. The patients included 16 women and 30 men, with a mean age of 53.4 years (range, 28-82 years). Forty patients had undergone cystectomy, and the remaining 6 had undergone transurethral bladder biopsy. Most tumors were located at the dome (n = 44); only 2 were located at both the dome and anterior wall. All tumors consisted of adenocarcinoma, including mucinous (n = 36), enteric (n = 7), not otherwise specified (n = 2), and signet ring cell (n = 1) types. Focal areas of signet ring cell features were present in 23 cases, but urothelial carcinoma in situ was not identified in any cases. The tumors invaded the muscularis propria (n = 8), perivesical adipose tissue (n = 27), and abdominal wall (n = 3). Twenty-five patients had died of cancer at a mean of 32 months (range, 12-74 months), and 21 patients were alive at a mean of 65 months (range, 7-230 months). The median cancer-specific survival time of urachal adenocarcinoma patients was 45 months, which was significantly longer than that of bladder urothelial carcinoma patients with similar-stage disease (P = .047). Patients' cancer-specific survival was associated with tumor stage according to the Sheldon, Mayo, and TNM staging systems. In conclusion, urachal carcinomas are predominantly composed of invasive adenocarcinomas, which commonly demonstrate mucinous features. Most tumors present at advanced stages but are still associated with a better survival rate than bladder urothelial carcinomas. PMID- 26364860 TI - The MNI data-sharing and processing ecosystem. AB - Neuroimaging has been facing a data deluge characterized by the exponential growth of both raw and processed data. As a result, mining the massive quantities of digital data collected in these studies offers unprecedented opportunities and has become paramount for today's research. As the neuroimaging community enters the world of "Big Data", there has been a concerted push for enhanced sharing initiatives, whether within a multisite study, across studies, or federated and shared publicly. This article will focus on the database and processing ecosystem developed at the Montreal Neurological Institute (MNI) to support multicenter data acquisition both nationally and internationally, create database repositories, facilitate data-sharing initiatives, and leverage existing software toolkits for large-scale data processing. PMID- 26364862 TI - The reliability of continuous brain responses during naturalistic listening to music. AB - Low-level (timbral) and high-level (tonal and rhythmical) musical features during continuous listening to music, studied by functional magnetic resonance imaging (fMRI), have been shown to elicit large-scale responses in cognitive, motor, and limbic brain networks. Using a similar methodological approach and a similar group of participants, we aimed to study the replicability of previous findings. Participants' fMRI responses during continuous listening of a tango Nuevo piece were correlated voxelwise against the time series of a set of perceptually validated musical features computationally extracted from the music. The replicability of previous results and the present study was assessed by two approaches: (a) correlating the respective activation maps, and (b) computing the overlap of active voxels between datasets at variable levels of ranked significance. Activity elicited by timbral features was better replicable than activity elicited by tonal and rhythmical ones. These results indicate more reliable processing mechanisms for low-level musical features as compared to more high-level features. The processing of such high-level features is probably more sensitive to the state and traits of the listeners, as well as of their background in music. PMID- 26364861 TI - MGH-USC Human Connectome Project datasets with ultra-high b-value diffusion MRI. AB - The MGH-USC CONNECTOM MRI scanner housed at the Massachusetts General Hospital (MGH) is a major hardware innovation of the Human Connectome Project (HCP). The 3T CONNECTOM scanner is capable of producing a magnetic field gradient of up to 300 mT/m strength for in vivo human brain imaging, which greatly shortens the time spent on diffusion encoding, and decreases the signal loss due to T2 decay. To demonstrate the capability of the novel gradient system, data of healthy adult participants were acquired for this MGH-USC Adult Diffusion Dataset (N=35), minimally preprocessed, and shared through the Laboratory of Neuro Imaging Image Data Archive (LONI IDA) and the WU-Minn Connectome Database (ConnectomeDB). Another purpose of sharing the data is to facilitate methodological studies of diffusion MRI (dMRI) analyses utilizing high diffusion contrast, which perhaps is not easily feasible with standard MR gradient system. In addition, acquisition of the MGH-Harvard-USC Lifespan Dataset is currently underway to include 120 healthy participants ranging from 8 to 90 years old, which will also be shared through LONI IDA and ConnectomeDB. Here we describe the efforts of the MGH-USC HCP consortium in acquiring and sharing the ultra-high b-value diffusion MRI data and provide a report on data preprocessing and access. We conclude with a demonstration of the example data, along with results of standard diffusion analyses, including q-ball Orientation Distribution Function (ODF) reconstruction and tractography. PMID- 26364864 TI - The contribution of geometry to the human connectome. AB - The human connectome is a topologically complex, spatially embedded network. While its topological properties have been richly characterized, the constraints imposed by its spatial embedding are poorly understood. By applying a novel resampling method to tractography data, we show that the brain's spatial embedding makes a major, but not definitive, contribution to the topology of the human connectome. We first identify where the brain's structural hubs would likely be located if geometry was the sole determinant of brain topology. Empirical networks show a widespread shift away from this geometric center toward more peripheral interconnected skeletons in each hemisphere, with discrete clusters around the anterior insula, and the anterior and posterior midline regions of the cortex. A relatively small number of strong inter-hemispheric connections assimilate these intra-hemispheric structures into a rich club, whose connections are locally more clustered but globally longer than predicted by geometry. We also quantify the extent to which the segregation, integration, and modularity of the human brain are passively inherited from its geometry. These analyses reveal novel insights into the influence of spatial geometry on the human connectome, highlighting specific topological features that likely confer functional advantages but carry an additional metabolic cost. PMID- 26364863 TI - The Function Biomedical Informatics Research Network Data Repository. AB - The Function Biomedical Informatics Research Network (FBIRN) developed methods and tools for conducting multi-scanner functional magnetic resonance imaging (fMRI) studies. Method and tool development were based on two major goals: 1) to assess the major sources of variation in fMRI studies conducted across scanners, including instrumentation, acquisition protocols, challenge tasks, and analysis methods, and 2) to provide a distributed network infrastructure and an associated federated database to host and query large, multi-site, fMRI and clinical data sets. In the process of achieving these goals the FBIRN test bed generated several multi-scanner brain imaging data sets to be shared with the wider scientific community via the BIRN Data Repository (BDR). The FBIRN Phase 1 data set consists of a traveling subject study of 5 healthy subjects, each scanned on 10 different 1.5 to 4 T scanners. The FBIRN Phase 2 and Phase 3 data sets consist of subjects with schizophrenia or schizoaffective disorder along with healthy comparison subjects scanned at multiple sites. In this paper, we provide concise descriptions of FBIRN's multi-scanner brain imaging data sets and details about the BIRN Data Repository instance of the Human Imaging Database (HID) used to publicly share the data. PMID- 26364865 TI - Assessing intracranial vascular compliance using dynamic arterial spin labeling. AB - Vascular compliance (VC) is an important marker for a number of cardiovascular diseases and dementia, which is typically assessed in the central and peripheral arteries indirectly by quantifying pulse wave velocity (PWV), and/or pulse pressure waveform. To date, very few methods are available for the quantification of intracranial VC. In the present study, a novel MRI technique for in-vivo assessment of intracranial VC was introduced, where dynamic arterial spin labeling (ASL) scans were synchronized with the systolic and diastolic phases of the cardiac cycle. VC is defined as the ratio of change in arterial cerebral blood volume (DeltaCBV) and change in arterial pressure (DeltaBP). Intracranial VC was assessed in different vascular components using the proposed dynamic ASL method. Our results show that VC mainly occurs in large arteries, and gradually decreases in small arteries and arterioles. The comparison of intracranial VC between young and elderly subjects shows that aging is accompanied by a reduction of intracranial VC, in good agreement with the literature. Furthermore, a positive association between intracranial VC and cerebral perfusion measured using pseudo-continuous ASL with 3D GRASE MRI was observed independent of aging effects, suggesting loss of VC is associated with a decline in perfusion. Finally, a significant positive correlation between intracranial and central (aortic arch) VC was observed using an ungated phase-contrast 1D projection PWV technique. The proposed dynamic ASL method offers a promising approach for assessing intracranial VC in a range of cardiovascular diseases and dementia. PMID- 26364867 TI - Review: domestic animal forensic genetics - biological evidence, genetic markers, analytical approaches and challenges. AB - This review highlights the importance of domestic animal genetic evidence sources, genetic testing, markers and analytical approaches as well as the challenges this field is facing in view of the de facto 'gold standard' human DNA identification. Because of the genetic similarity between humans and domestic animals, genetic analysis of domestic animal hair, saliva, urine, blood and other biological material has generated vital investigative leads that have been admitted into a variety of court proceedings, including criminal and civil litigation. Information on validated short tandem repeat, single nucleotide polymorphism and mitochondrial DNA markers and public access to genetic databases for forensic DNA analysis is becoming readily available. Although the fundamental aspects of animal forensic genetic testing may be reliable and acceptable, animal forensic testing still lacks the standardized testing protocols that human genetic profiling requires, probably because of the absence of monetary support from government agencies and the difficulty in promoting cooperation among competing laboratories. Moreover, there is a lack in consensus about how to best present the results and expert opinion to comply with court standards and bear judicial scrutiny. This has been the single most persistent challenge ever since the earliest use of domestic animal forensic genetic testing in a criminal case in the mid-1990s. Crime laboratory accreditation ensures that genetic test results have the courts' confidence. Because accreditation requires significant commitments of effort, time and resources, the vast majority of animal forensic genetic laboratories are not accredited nor are their analysts certified forensic examiners. The relevance of domestic animal forensic genetics in the criminal justice system is undeniable. However, further improvements are needed in a wide range of supporting resources, including standardized quality assurance and control protocols for sample handling, evidence testing, statistical analysis and reporting that meet the rules of scientific acceptance, reliability and human forensic identification standards. PMID- 26364866 TI - Long-term visual damage after acute methanol poisonings: Longitudinal cross sectional study in 50 patients. AB - CONTEXT: Visual disturbances due to the toxic effect of formic acid in acute methanol poisonings are generally transient. The subjective symptoms of visual toxicity may resolve within few weeks and fundoscopic signs of acute optic neuropathy subside within 1-2 months; therefore, the prevalence of long-term visual sequelae in the population of survivors of poisonings may be underestimated. OBJECTIVE: To study the prevalence and character of long-term visual sequelae of acute methanol poisonings based on the data from the Czech mass methanol outbreak in 2012. PATIENTS AND METHODS: A total of 50 patients with confirmed methanol poisoning were included in this longitudinal cross-sectional study, median age: 48 (range, 23-73) years. The following tests were performed: optical coherence tomography or OCT with evaluation of the retinal nerve fibers layer (RNFL), visual evoked potentials (VEP), magnetic resonance imaging (MRI) of brain, complete ocular examination (visual acuity/field, color vision, contrast sensitivity, and fundus), neurological examinations, and biochemical tests. RESULTS: Of 50 patients, 7/50 (14%) were discharged with diagnosed visual sequelae and 6/50 (12%) were discharged with both visual and central nervous system sequelae of poisoning. On the follow-up examination, 20/50 (40%) of the patients had long-term visual sequelae, with 8% of blindness. A total of 38% of the patients had abnormal (28% borderline) findings on RNFL, and 40% had abnormal (18% borderline) VEP. Among the patients discharged without detected visual sequelae, 8/37 (22%) had abnormal RNFL and VEP. Patients with visual sequelae had brain lesions more often (70% vs. 27%, p < 0.01). MRI identified optic nerve lesions in 2/20 cases with abnormal VEP only. The groups with and without visual sequelae differed in serum methanol, ethanol, HCO3-, formate, pH, anion gap, and base deficit (all p < 0.01). Visual disturbances on admission and coma were more prevalent in the patients with visual sequelae (p < 0.05). Patients with positive serum ethanol on admission were 93% less likely to have optical axonal damage (OR: 0.07 (95% CI: 0.01-0.8); p < 0.05). No association was found between visual sequelae and type of antidote administered, mode of hemodialysis, or folate substitution. Pre-hospital administration of ethanol seemed beneficial: these patients were 90% less likely to have abnormal RNFL findings (OR: 0.10 (95% CI: 0.02-0.52); p < 0.01). CONCLUSIONS: The long-term visual sequelae were clearly underestimated on discharge, suggesting a significantly higher amount of patients with long-term sequelae than earlier reported. Thorough examinations before discharge and during follow-up will likely uncover a higher morbidity also after methanol poisonings in general. PMID- 26364868 TI - The effect of iron plaque on lead translocation in soil-Carex cinerascens kukenth. system. AB - A pot experiment was conducted to investigate the effect of iron plaque on Pb uptake by and translocation in Carex cinerascens Kukenth. grown under open-air conditions. Using Scanning Electron Microscopy and Energy Dispersive X-Ray Spectrometry, iron plaque was present as an amorphous coating on root surfaces with uneven distribution. The amount of iron plaque increased significantly with increasing Fe additions regardless of Pb additions. The presence of iron plaque on the root surface of Carex cinerascens Kukenth. increased the concentrations of Pb adsorbed by iron plaque. The Pb percentage in whole roots increased by 14.52% at 500 mg kg(-1) Fe treatment than at 0 mg kg(-1) Fe, and the distribution coefficient (DC) of Pb and translocation factor (TF) root increased with Fe additions, but translocation factor (TF) shoot decreased with Fe additions. The results suggested that iron plaque could promote the translocation of Pb from soil to roots to some extent, and it played a role to reduce heavy metals pollution of Poyang Lake wetland. PMID- 26364869 TI - A custom-made mandibular repositioning device for obstructive sleep apnoea hypopnoea syndrome: the ORCADES study. AB - BACKGROUND: Mandibular repositioning devices (MRDs) are usually recommended as the first therapy option in patients with mild-to-moderate obstructive sleep apnoea (OSA). However, data on the long-term efficacy of MRDs are limited, not only in OSA patients who are noncompliant with continuous positive airway pressure (CPAP) but also in those with more severe OSA. The ORCADES study aimed to prospectively determine the long-term efficacy and tolerability of two custom made Narval(TM) MRDs for obstructive sleep apnoea-hypopnoea syndrome (OSAHS) patients. The interim 3- to 6-month data are reported. METHODS: Eligible patients had OSAHS and had refused or were noncompliant with prescribed CPAP. Outcome measurements after gradual mandibular advancement titration included: apnoea hypopnoea index (AHI), oxygen saturation, sleepiness, symptoms, quality of life, side effects and compliance. RESULTS: A total of 369 patients were included. Overall, MRD treatment was successful (>=50% decrease in AHI) in 76.2% of the participants; complete response (AHI <10/h) was achieved in 63.5%. Severe OSAHS was effectively treated (AHI <15/h) in about 60% of the participants; 38% had complete symptom resolution. Mandibular repositioning devices significantly decreased subjective sleepiness, eliminated symptoms and improved quality of life. They were well tolerated and compliance was excellent. Only 8% of the participants stopped MRD treatment due to side effects. CONCLUSION: Custom-made Narval(TM) MRDs are effective for mild to severe OSA in patients who refuse or are noncompliant with CPAP. They are well tolerated and have excellent compliance. PMID- 26364870 TI - Triggering the apoptosis of targeted human renal cancer cells by the vibration of anisotropic magnetic particles attached to the cell membrane. AB - Cancer cells develop resistance to chemotherapy, and the side effects encountered seriously limit the effectiveness of treatments. For these reasons, the search for alternative therapies that target cancer cells without affecting healthy tissues is currently one of the most active areas of research on cancer. The present study focuses on a recently proposed approach for cancer cell destruction based on the targeted triggering of cancer cell spontaneous death through the mechanical vibration of anisotropic magnetic micro/nanoparticles attached to the cell membranes at low frequencies (~20 Hz) and in weak magnetic fields (~30 mT). The study was conducted in vitro, on human renal cancer cells with superparamagnetic-like particles. Three types of such particles made of NiFe or magnetite were prepared and characterized (either synthetic antiferromagnetic, vortex or polycrystalline with random grain anisotropy). The triggering of the apoptosis of these cancer cells was demonstrated with NiFe vortex particles and statistically characterized by flow-cytometry studies. The death pathway via apoptosis and not necrosis was identified by the clear observation of caspase activation. PMID- 26364871 TI - Transplant to treatment-free remission: the evolving view of 'cure' in chronic myeloid leukemia. AB - Before the introduction of the BCR-ABL1 tyrosine kinase inhibitor (TKI) imatinib, chronic myeloid leukemia (CML) was the leading indication for allogeneic hematopoietic stem cell transplant (HSCT), and allogeneic HSCT remains the only treatment recognized as curative for CML. The success of imatinib and other TKIs (e.g., nilotinib, dasatinib) has made allogeneic HSCT a later-line therapy that is reserved only for advanced-phase, high-risk, or TKI-resistant patients with CML. Accumulating evidence from clinical trials investigating treatment-free remission suggests that TKIs may also provide an operational cure for some patients with CML. Herein, we discuss the concept of cure in CML and the current roles of both HSCT and TKIs in the treatment of CML. PMID- 26364872 TI - AlGaN/GaN Metal-Oxide-Semiconductor High-Electron-Mobility Transistor with Polarized P(VDF-TrFE) Ferroelectric Polymer Gating. AB - Effect of a polarized P(VDF-TrFE) ferroelectric polymer gating on AlGaN/GaN metal oxide-semiconductor high-electron-mobility transistors (MOS-HEMTs) was investigated. The P(VDF-TrFE) gating in the source/drain access regions of AlGaN/GaN MOS-HEMTs was positively polarized (i.e., partially positively charged hydrogen were aligned to the AlGaN surface) by an applied electric field, resulting in a shift-down of the conduction band at the AlGaN/GaN interface. This increases the 2-dimensional electron gas (2-DEG) density in the source/drain access region of the AlGaN/GaN heterostructure, and thereby reduces the source/drain series resistance. Detailed material characterization of the P(VDF TrFE) ferroelectric film was also carried out using the atomic force microscopy (AFM), X-ray Diffraction (XRD), and ferroelectric hysteresis loop measurement. PMID- 26364873 TI - Electronic Olfactory Sensor Based on A. mellifera Odorant-Binding Protein 14 on a Reduced Graphene Oxide Field-Effect Transistor. AB - An olfactory biosensor based on a reduced graphene oxide (rGO) field-effect transistor (FET), functionalized by the odorant-binding protein 14 (OBP14) from the honey bee (Apis mellifera) has been designed for the in situ and real-time monitoring of a broad spectrum of odorants in aqueous solutions known to be attractants for bees. The electrical measurements of the binding of all tested odorants are shown to follow the Langmuir model for ligand-receptor interactions. The results demonstrate that OBP14 is able to bind odorants even after immobilization on rGO and can discriminate between ligands binding within a range of dissociation constants from K(d)=4 MUM to K(d)=3.3 mM. The strongest ligands, such as homovanillic acid, eugenol, and methyl vanillate all contain a hydroxy group which is apparently important for the strong interaction with the protein. PMID- 26364874 TI - RIFM fragrance ingredient safety assessment, Benzyl alcohol, CAS Registry Number 100-51-6. PMID- 26364875 TI - Evaluation of the in vivo genotoxicity of Allura Red AC (Food Red No. 40). AB - Allura Red AC (Food Red No. 40) is a red azo dye that is used for food coloring in beverage and confectionary products. However, its genotoxic properties remain controversial. To clarify the in vivo genotoxicity, we treated mice with Allura Red AC and investigated the induction of DNA damage (liver, glandular stomach), clastogenicity/anuegenicity (bone marrow), and mutagenicity (liver, glandular stomach) using Comet assays, micronucleus tests, and transgenic gene mutation assays, respectively. All studies were conducted in accordance with the Organization for Economic Co-operation and Development (OECD) guideline. Although Allura Red AC was administered up to the maximum doses recommended by the OECD guideline, no genotoxic effect was observed in any of the genotoxic endpoints. These data clearly show no evidence of in vivo genotoxic potential of Allura Red AC administered up to the maximum doses in mice. PMID- 26364876 TI - RIFM fragrance ingredient safety assessment, alpha-butylcinnamaldehyde, CAS Registry Number 7492-44-6. AB - The use of this material under current use conditions is supported by the existing information. This material was evaluated for genotoxicity, repeated dose toxicity, developmental toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity, skin sensitization potential, as well as, environmental safety. Repeated dose toxicity was determined to have the most conservative systemic exposure derived NO[A]EL of 29.9 mg/kg/day. A dietary 14-week subchronic toxicity study conducted in rats on a suitable read across analog resulted in a MOE of 3784810 while considering 9.54% absorption from skin contact and 100% from inhalation. A MOE of > 100 is deemed acceptable. PMID- 26364877 TI - Evaluation of serum and liver toxicokinetics for furan and liver DNA adduct formation in male Fischer 344 rats. AB - Furan is a food processing contaminant found in many common cooked foods that induces liver toxicity and liver cancer in animal models treated with sufficient doses. The metabolism of furan occurs primarily in the liver where CYP 2E1 produces a highly reactive bis-electrophile, cis-2-butene-1,4-dial (BDA). BDA reacts with nucleophilic groups in amino acids and DNA in vitro to form covalent adducts. Evidence for BDA-nucleoside adduct formation in vivo is limited but important for assessing the carcinogenic hazard of dietary furan. This study used controlled dosing with furan in Fischer 344 rats to measure serum and liver toxicokinetics and the possible formation of BDA-nucleoside adducts in vivo. After gavage exposure, furan concentrations in the liver were consistently higher than those in whole blood (~6-fold), which is consistent with portal vein delivery of a lipophilic compound into the liver. Formation of BDA-2' deoxycytidine in furan-treated rat liver DNA was not observed using LC/MS/MS after single doses as high as 9.2 mg/kg bw or repeated dosing for up to 360 days above a consistent background level (1-2 adducts per 10(8) nucleotides). This absence of BDA-nucleoside adduct formation is consistent with the general lack of evidence for genotoxicity of furan in vivo. PMID- 26364878 TI - Rotational thromboelastometry in the diagnosis of coagulopathy in major pediatric surgical operations. AB - OBJECTIVES: To examine the correlation between rotational thromboelastometry (ROTEM) and coagulopathy after major pediatric surgical operations. METHODS: From November 2013 until April 2015, pediatric cases who underwent major noncardiac surgeries and met the coagulopathy-risk criteria were reviewed for postoperative clinically significant coagulopathy (CSC). Two ROTEM studies, EXTEM and INTEM, were performed at the immediately postoperatively without the results being taken into any clinical decision making. RESULTS: Seventy-seven operations on 73 patients were included in this analysis. CSC occurred following 24 operations (32%) with a significantly higher incidence when a patient had a higher coagulopathy risk. On univariate analysis, evidence of diffuse bleeding in the operative field and massive bleeding were the 2 parameters with the strongest association with CSC. INTEM and EXTEM had specificities in diagnosing CSC of 75.5% and 94.3%, respectively. When each individual EXTEM and INTEM item was analyzed against CSC using ROC analysis, clot forming time (CFT) gave the largest under the curve area. The cut-off CFTs that gave the highest sensitivity and specificity in this study were 120seconds for EXTEM and 100seconds for INTEM. CONCLUSION: Postoperative coagulopathy is a risk that should always be considered in pediatric surgical operations. Thromboelastometry can be a hemostatic test providing high predictive value for this condition. PMID- 26364879 TI - Use of small intestinal submucosal and acellular dermal matrix grafts in giant omphaloceles in neonates and a rabbit abdominal wall defect model. AB - BACKGROUND: The described surgical strategies for the management of omphalocele include primary closure, staged closure, and delayed closure. A primary repair is not suitable for all giant omphaloceles. We implanted two grafts, small intestinal submucosal (SIS) and acellular dermal matrix (ADM) onto abdominal wall defects in neonates to study the safety and efficacy of SIS and ADM graft techniques for initial closure of giant omphaloceles in infants, and we also implanted these grafts onto abdominal wall defects in an animal model. METHODS: Twenty-four patients with giant omphaloceles were divided into two groups (ADM group, 12 patients; SIS group, 12 patients). The operative time, skin healing time postoperatively, and the incidence of skin infections, and abdominal wall hernias were observed. In the rabbit animal model, bilateral full-thickness incisions were made through the rabbit rectus abdominus muscles and a 2*4cm longitudinal whole layer defect was created on either the left or right lateral anterior abdominal wall. A four-layered variant of the SIS graft was used to repair the right abdominal defect; ADM was used to repair the left. Tensile strength was measured using an Instron tensiometer. Electron scanning and light microscopy were used to evaluate neovascularization, collagen deposition, and muscle fibers at 2, 4, 8, and 16weeks postimplantation. RESULTS: In the neonatal patients, there was no statistically significant difference between the two groups with respect to operative time, skin healing time postoperatively, the incidence of skin infections, or abdominal wall hernias. In the SIS group, only one patient developed a skin infection, which led to skin necrosis and sloughing. In the ADM group, four patients developed skin infection postoperatively, and the patch was gradually removed. In the animal study, there was no significant difference between the mean breaking strength of ADM versus SIS repairs. Scanning electron and light microscopy showed collagen deposition, increased vascularization, fibroblasts, and muscular regeneration in both SIS and ADM repairs. SEM showed that the SIS graft was absorbed, while ADM was not. Light microscopy showed foreign body macrophages in ADM, but not in the SIS repairs. CONCLUSION: SIS and ADM grafts adequately enhance healing with a low complication rate. Compared with ADM grafts, SIS is absorbable, induces less inflammation, and is more biocompatible, and therefore might be more useful and suitable for closure of abdominal wall defects. PMID- 26364880 TI - Endoscopic esophageal substitution for pure esophageal atresia and wide gap esophageal atresia: A report of five cases with minimum follow-up of twelve months. AB - AIM: The aim of the study is to report feasibility and safety of endoscopic esophageal substitution in infants with pure esophageal atresia and wide gap tracheoesophageal fistula with a minimum one year follow-up. MATERIALS AND METHODS: This prospective study was conducted from January 2012 for twenty four consecutive months at Apollo Hospital, New Delhi. All babies either followed up or referred for esophageal substitution without any history of mediastinitis or associated major congenital anomaly and weighing greater than 6kg were to be included in the study. The indication, intraoperative details, operative approach, conversion to open, esophageal substitute, postoperative ventilation, ICU and hospital stay, time to solid foods, morbidity and mortality were recorded. Informed consent was obtained from all the parents and ethical clearance was obtained for the study from the hospital ethical committee. Postoperatively babies were followed up monthly for first six months, 3 monthly for next six months and annually thereafter. RESULTS: Between January 2012 and December 2013, in the two year period six infants were admitted for laparoscopic gastric transposition. In five patients the procedure was completed by the laparoscopic approach and one required conversion to open surgery owing to dense adhesions. The age range at the time of surgery was from 8months to 12months with a mean age of 10months. Four patients had pure esophageal atresia (type A) and two had wide gap esophageal atresia with distal tracheoesophageal atresia (type C). Five had primary esophagostomy and gastrostomy as a newborn, the sixth had postoperative anastomotic leak and required subsequent diversion. The mean operating time was 194minutes (range 170-210minutes). The mean stay in ICU was 7days with a range of 4-12days. All patients were ventilated in the postoperative period for an average of 5days with a range of 4-7days. One patient had prolonged gastric ileus which delayed the oral feeds by 14days. The mean time to start the oral feeds was 8days with a range of 6-14days. The mean hospital stay was 19.6days (range 16-23days). Early complications were pneumonia and pleural effusion in one patient. One patient developed anastomotic stricture which was amenable to dilatation. One patient had leak from esophagogastric anastomosis which healed spontaneously. All children are now orally fed, swallow without difficulty, and parents report an excellent cosmetic outcome. The follow-up ranges from 12 to 36months. CONCLUSION: The initial results of endoscopic esophageal substitution are encouraging and easily comparable to the outcome of open surgery with all the attendant benefits of minimally invasive approach. PMID- 26364881 TI - Peripherally inserted central catheter in neonates: A safe and easy insertion technique. AB - PURPOSE: Peripherally inserted central catheters (PICC) are used extensively in neonates. However, insertion of these thinnest catheters is a very delicate procedure. We developed an easy and safe insertion technique for 2-French (F) PICCs with a new fine-tipped introducer cannula created without modifying commercial products by advancing a 24-gauge peripheral venous cannula through a half-peeled (20-gauge) introducer cannula. We evaluated neonates treated with our new PICC insertion technique. METHODS: Information was collected retrospectively on all 32 2-F PICCs inserted during the 4-year period from November 2010 to November 2014. We monitored neonates, recording the success rate of placement, number of insertion attempts, reasons for removal, and complications. RESULTS: In total, 32 2-F PICCs were placed in 31 patients (19 (61%) males and 12 (39%) females; median age 7 (range: 1-36) days, median weight 2200 (range: 800-4100) g) using the new technique. The vein accessed most commonly was the long saphenous vein (87%). The duration of catheterization was 10.3 +/- 4.2 days. Almost all PICCs were inserted successfully (32/33, success rate 97%) and in the first venipuncture (28/32, 88%). Of the PICCs, 81% were removed after completion of therapy or upon death. Two minor bleeding complications were noted at the insertion site. CONCLUSIONS: This novel technique is an easy and safe way of inserting a 2-F PICC in neonates. It can be used by anyone in a neonatal unit who can insert a 24-gauge peripheral venous access. PMID- 26364882 TI - Tip-induced nanoreactor for silicate. AB - Nanoscale scientific issues have attracted an increasing amount of research interest due to their specific size-effect and novel structure-property. From macro to nano, materials present some unique chemical reactivity that bulk materials do not own. Here we introduce a facile method to generate silicate with nanoscale control based on the establishment of a confined space between a meso/nanoscale tungsten tip and a smooth silica/silicon substrate. During the process, local water-like droplets deposition can be obviously observed in the confinement between the Si/SiO2 surfaces and the KOH-modified tungsten tip. By the combination of in-situ optical microscopy and Raman spectroscopy, we were able to take a deep insight of both the product composition and the underlying mechanism of such phenomena. It was indicated that such nanoreactor for silicate could be quite efficient as a result of the local capillarity and electric field effect, with implications at both nano and meso scales. PMID- 26364883 TI - Understanding Mycobacterium avium subspecies hominissuis microaggregate mediated pathogenesis. AB - Mycobacterium avium subspecies hominissuis (MAH) is an opportunistic pathogen and causes nontuberculous infections in immune compromised individuals, an emerging problem that has been recognized worldwide. Understanding the pathogenesis of this organism is important as better treatment and prevention options are needed. Microaggregates form when two or more bacterial cells join at a surface. MAH forms micgroaggregates to promote its entry in to epithelial cells and cause infection. The mechanisms involved in the interaction between the microaggregate and the host are becoming clearer as the molecules involved in this process are being uncovered. Microaggregate Invasion Protein-1 (MIP-1) is now described as having a major role in the invasion of epithelial cells by MAH. PMID- 26364884 TI - CD44, SHH and SOX2 as novel biomarkers in esophageal cancer patients treated with neoadjuvant chemoradiotherapy. AB - BACKGROUND AND PURPOSE: Neoadjuvant chemoradiotherapy (nCRT) improves survival in esophageal cancer (EC) patients, but the response to treatment is heterogeneous and little is known regarding prognostic and predictive markers in these patients. CD44, SOX2 and SHH have been implicated in resistance to CRT, possibly through an association with a cancer stem cell phenotype. MATERIAL AND METHODS: 101 EC patients treated with nCRT and surgery were included. Sufficient pre treatment biopsy material was present in 71 patients, of which 53 patients were non-complete responders on nCRT (nCR). Protein expression was examined using immunohistochemistry (IHC). Prognostic factors were determined using Cox regression analysis for disease free survival (DFS) and cause specific survival (CSS) in the complete cohort, the pre-treatment biopsies group and post-treatment nCR group. RESULTS: Low CD44 expression in the nCR group was an independent prognostic factor for both DFS and CSS (DFS HR 2.81, p=0.002 and CSS HR 3.48, p=0.002). Absent SOX2 expression in pretreatment biopsies was related to systemic recurrence (p=0.029) while low SHH in pretreatment biopsies was an independent prognostic factor for a poor DFS (HR 2.27, p=0.036). No relation between marker expression and response to nCRT was observed. CONCLUSIONS: Low expression of CD44 and SHH are associated with a poor survival outcome in EC patients treated with nCRT. PMID- 26364885 TI - The influence of gastric filling instructions on dose delivery in patients with oesophageal cancer: A prospective study. AB - PURPOSE: To evaluate whether adaptive radiotherapy for unaccounted stomach changes in patients with adenocarcinoma of the gastroesophageal junction (GEJ) is necessary and whether dose differences could be prevented by giving patients food and fluid instructions before treatment simulation and radiotherapy. MATERIAL AND METHODS: Twenty patients were randomly assigned into two groups: patients with and without instructions about restricting food and fluid intake prior to radiotherapy simulation and treatment. Redelineation and offline recalculation of dose distributions based on cone-beam computed tomography (n=100) were performed. Dose-volume parameters were analysed for the clinical target volume extending into the stomach. RESULTS: Four patients who did not receive instructions had a geometric miss (0.7-12 cm(3)) in only one fraction. With instructions, 3 out of 10 patients had a geometric miss (0.1-1.9 cm(3)) in one (n=2) or two (n=1) fractions. The V95% was reduced by more than 5% for one patient, but this underdosage was in an in-air region without further clinical importance. CONCLUSIONS: Giving patients food and fluid instructions for the treatment of GEJ cancer offers no clinical benefit. Using a planning target volume margin of 1cm implies that there is no need for adaptive radiotherapy for GEJ tumours. PMID- 26364886 TI - Tumour delineation in oesophageal cancer - A prospective study of delineation in PET and CT with and without endoscopically placed clip markers. AB - PURPOSE: The objective was to analyse the value of F-18-fluorodesoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for delineation of the Gross Tumour Volumes (GTVs) in primary radiotherapy of oesophageal cancer. METHOD: 20 consecutive and prospective patients (13 men, 7 women) underwent FDG PET/CT for initial staging and radiation treatment planning. After endoscopy guided clipping of the tumour another CT study was acquired. The CT and the FDG PET/CT were registered with a rigid and a non-rigid registration algorithm to compare the overlap between GTV contours defined with the following methods: manual GTV definition in (1) the CT image of the FDG-PET/CT, (2) the PET image of the FDG-PET/CT, (3) the CT study based on endoscopic clips (CT clip), and (4) in the PET-data using different semi-automatic PET segmentation algorithms including a gradient-based algorithm. The absolute tumour volumes, tumour length in cranio caudal direction, as well as the overlap with the reference volume (CT-clip) were compared for all lesions and separately for proximal/distal tumours. RESULTS: In 6 of the patients, FDG-PET/CT discovered previously unknown tumour locations, which resulted in either altered target volumes (n=3) or altered intent of treatment from curative to palliative (n=3) by upstaging to stage IV. For tumour segmentation a large variability between all algorithms was found. For the absolute tumour volumes with CT-clip as reference, no single PET-based segmentation algorithm performed better compared to using the manual CT delineation alone. The best correlation was found between the CT-clip and the gradient based segmentation algorithm (PET-edge, R(2)=0.84) as well as the manual CT-delineation (CT-manual R(2)=0.89). Non-rigid registration between CT and image FDG-PET/CT did not decrease variability between segmentation methods compared to rigid registration statistically significant. For the analysis of tumour length no homogeneous correlation was found. CONCLUSION: Whereas FDG-PET was highly relevant for staging purposes, CT imaging with clipping of the tumour extension remains the gold standard for GTV delineation. PMID- 26364888 TI - Heteroepitaxially grown zeolitic imidazolate framework membranes with unprecedented propylene/propane separation performances. AB - Propylene/propane separation is one of the most challenging separations, currently achieved by energy-intensive cryogenic distillation. Despite the great potential for energy-efficient membrane-based separations, no commercial membranes are currently available due to the limitations of current polymeric materials. Zeolitic imidazolate framework, ZIF-8, with the effective aperture size of ~4.0 A, has been shown to be very promising for propylene/propane separation. Despite the extensive research on ZIF-8 membranes, only a few reported ZIF-8 membranes have displayed good propylene/propane separation performances presumably due to the challenges of controlling the microstructures of polycrystalline membranes. Here we report the first well-intergrown membranes of ZIF-67 (Co-substituted ZIF-8) by heteroepitaxially growing ZIF-67 on ZIF-8 seed layers. The ZIF-67 membranes exhibited impressively high propylene/propane separation capabilities. Furthermore, when a tertiary growth of ZIF-8 layers was applied to heteroepitaxially grown ZIF-67 membranes, the membranes exhibited unprecedentedly high propylene/propane separation factors of ~200 possibly due to enhanced grain boundary structure. PMID- 26364887 TI - Modulation of therapeutic sensitivity by human papillomavirus. AB - Human papillomaviruses (HPVs) are small double-stranded DNA viruses that pose significant public health concerns as the causative agent of approximately 5% of worldwide cancers. The HPV oncogenes E6 and E7 play key roles in carcinogenesis. In the last 15years there has been a significant increase in the incidence of HPV related head and neck cancers arising primarily in the oropharynx. Patients with HPV-positive head and neck cancers (HNCs) have a significantly improved prognosis compared to those with HPV-negative disease. In this review we will discuss data suggesting how HPV oncogenes modulate both the intrinsic radiation sensitivity of HNCs and also have important effects upon the tumor microenvironment. Together, these findings contribute to the improved outcomes seen in patients with HPV positive HNC. PMID- 26364889 TI - Objective Evaluation of Otoscopy Skills Among Family and Community Medicine, Pediatric, and Otolaryngology Residents. AB - INTRODUCTION: The objective of this study is to evaluate and compare the perceived need for otolaryngology training and otoscopy diagnostic skills in primary care (Family and Community Medicine, Pediatric Medicine), and Otolaryngology Head and Neck Surgery (OTO-HNS) postgraduate trainees. Participant otoscopy skills were evaluated using the OtoSim simulator. METHODS: Family and Community Medicine, Pediatric, and OTO-HNS residents were recruited. Each resident participated in 3 separate otoscopy training and assessment sessions. The ability to correctly identify middle ear pathology was objectively evaluated using OtoSimTM. Pretest, posttest, and 3-month retention test results were compared among residents in a paired comparison paradigm. Survey data assessing exposure to OTO-HNS during undergraduate and postgraduate training were also collected. RESULTS: A total of 57 residents participated in the study. All residents reported limited exposure to OTO-HNS during undergraduate medical training. Primary care trainees performed poorly on pretest assessments (30% +/- 7.8%; 95% CI). Significant improvement in diagnostic accuracy was demonstrated following a single 1-hour teaching session (30%-62%; p < 0.001). Primary care residents demonstrated a significant decrease in diagnostic accuracy at a 3-month follow-up assessment (62%-52%, p < 0.001). Self-perceived comfort with otology was poorly correlated to pretest performance among primary care trainees (r = 0.26) and showed a stronger positive correlation among OTO-HNS trainees (r = 0.56). CONCLUSIONS: A single teaching session with an otoscopy simulator significantly improved diagnostic accuracy in primary care and OTO-HNS trainees. Improved performance is susceptible to deterioration at 3 months if acquired skills are not frequently used. Self-perceived comfort with otology may not be an accurate predictor of otoscopic diagnostic skill. PMID- 26364890 TI - Dominant mechanisms of primary resistance differ from dominant mechanisms of secondary resistance to targeted therapies. AB - The effectiveness of targeted therapies is currently limited, as almost all patients eventually acquire resistance within year/year and a half from therapy initiation and a small subset of a patients fail to respond at all, demonstrating intrinsic resistance. The aim of this review was to determine the potential common features and differences between the mechanisms of intrinsic and acquired resistance to targeted therapies by analyzing established resistance-generating alterations for ten FDA-approved targeted drugs. The frequency of alterations underlying intrinsic and acquired resistance shows distinctive pattern, where dominant mechanisms of intrinsic resistance include aberrations of signals downstream or upstream of the targeted protein and dominant mechanisms of acquired resistance refer to lesions in the target itself or alterations of signals at target-level that can mimic or compensate for target function. It appears that during the evolution of acquired resistance, the tumor cell is inclined to preserve the same oncogene addiction on a targeted protein it had prior to drug administration. On the other hand, intrinsic resistance develops early in tumorogenesis and is based on randomly selected mutated signals between targeted and non-targeted signaling pathways, leading to the acquisition of cancer hallmarks. In general, there is an overlap between the mechanisms of intrinsic and acquired resistance, but the occurrence frequency and distribution of alterations underlying intrinsic and acquired resistance to targeted therapies are significantly different. Focus should be placed on different group of genes in pursuing predictive markers for intrinsic and acquired resistance to targeted therapies. PMID- 26364891 TI - Signaling mechanisms of resistance to EGFR- and Anti-Angiogenic Inhibitors cancer. AB - Colorectal cancer is among four most common malignancies and the second leading cause of cancer death in the western world. Epidermal Growth Factor Receptor (EGFR) and Vascular Endothelial Growth Factor (VEGF) are often overexpressed in colorectal cancer and are associated with inferior outcomes. More recently, further improvements in survival have occurred due to the use of novel targeted therapies such EGFR Tyrosine Kinase Inibitors (EGFR-TKIs), EGFR monoclonal antibodies (EGFR-mAb), and VEGF antibodies. Despite the initial clinical efficacy of these inhibitors in such cancer, resistance invariably develops, typically within 1 to 2 years. Over the past several years, multiple molecular mechanisms of resistance have been identified, and some common themes have emerged. One is the development of resistance mutations in the drug target and another it is activation of alternative signaling of key downstream pathways despite sustained inhibition of the original drug target. In this mini-review, we summarize the concepts underlying EGFR- and VEGF-mediated resistance, the specific examples known to date, and the challenges of applying this knowledge to develop improved therapeutic strategies to prevent or overcome resistance. PMID- 26364892 TI - Effects of cognitive speed of processing training on a composite neuropsychological outcome: results at one-year from the IHAMS randomized controlled trial. AB - BACKGROUND: Age-related cognitive decline is common and well-documented. Cognitive speed of processing training (SOPT) has been shown to improve trained abilities (Useful Field of View; UFOV), but transfer to individual non-trained cognitive outcomes or neuropsychological composites is sparse. We examine the effects of SOPT on a composite of six equally weighted tests--UFOV, Trail-making A and B, Symbol Digit Modality, Controlled Oral Word Association, Stroop Color and Word, and Digit Vigilance. METHODS: 681 patients were randomized separately within two age-bands (50-64, >= 65) to three SOPT groups (10 initial hours on site, 10 initial hours on-site plus 4 hours of boosters, or 10 initial hours at home) or an attention-control group (10 initial hours on-site of crossword puzzles). At one-year, 587 patients (86.2%) had complete data. A repeated measures linear mixed model was used. RESULTS: Factor analysis revealed a simple unidimensional structure with Cronbach's alpha of 0.82. The time effect was statistically significant (p < 0.001; etap2 = 0.246), but the time by treatment group (p = 0.331), time by age-band (p = 0.463), and time by treatment group by age-band (p = 0.564) effects were not. CONCLUSION: Compared to the attention control group who played a computerized crossword puzzle game, assignment to 10 14 hours of SOPT did not significantly improve a composite measure of cognitive abilities. PMID- 26364893 TI - Gaussian private quantum channel with squeezed coherent states. AB - While the objective of conventional quantum key distribution (QKD) is to secretly generate and share the classical bits concealed in the form of maximally mixed quantum states, that of private quantum channel (PQC) is to secretly transmit individual quantum states concealed in the form of maximally mixed states using shared one-time pad and it is called Gaussian private quantum channel (GPQC) when the scheme is in the regime of continuous variables. We propose a GPQC enhanced with squeezed coherent states (GPQCwSC), which is a generalization of GPQC with coherent states only (GPQCo) [Phys. Rev. A 72, 042313 (2005)]. We show that GPQCwSC beats the GPQCo for the upper bound on accessible information. As a subsidiary example, it is shown that the squeezed states take an advantage over the coherent states against a beam splitting attack in a continuous variable QKD. It is also shown that a squeezing operation can be approximated as a superposition of two different displacement operations in the small squeezing regime. PMID- 26364895 TI - Chemotherapy options for previously untreated acute myeloid leukemia. AB - INTRODUCTION: Intensive chemotherapy with cytarabine and an anthracycline for untreated acute myeloid leukemia (AML) has remained largely unchanged over the past 40 years, despite many large trials examining the choice and dosing of these agents. AREAS COVERED: We will review the major published clinical trials for untreated AML that have established the dosing choice and schedule for intensive therapy, as well as trials for patients not eligible for more intensive therapy. We will also discuss treatment considerations for subgroups of patients. EXPERT OPINION: While one or two cycles of anthracycline and cytarabine-based combination regimens remain the standard of care for younger and older patients with AML deemed fit to receive induction chemotherapy, controversy remains regarding the optimal selection and dosing schedule for anthracyclines. Low intensity regimens, such as low-dose cytarabine and hypomethylating agents, can achieve a complete response even with adverse risk features, and can be used in a fit subset of older patients not eligible for clinical trial or transplant. Incorporation of new targeted agents, such as tyrosine kinase and small-molecule inhibitors, combined with better selection of drugs for unique patient cohorts, will likely be necessary to substantially improve outcomes in AML. PMID- 26364896 TI - The use of stimulants and atomoxetine in adults with comorbid ADHD and bipolar disorder. AB - INTRODUCTION: Attention deficit/hyperactivity disorder (ADHD) persists into adulthood in about 50% of the affected children, with high rates of comorbidity with bipolar disorder (BD). Stimulants and atomoxetine (ATX) are effective treatments for ADHD, but their use in adults with comorbid BD (ADHD-BD) has not been extensively studied and may be problematic. AREAS COVERED: The aim of the paper is to summarize the available literature regarding the use of these medications in ADHD-BD adult patients. Results of randomized-controlled and open label trials, case reports, and case series are reviewed. We also reviewed data relative to some specific issues of this comorbidity in adults, especially substance use disorder, malingering, and stimulants misuse. EXPERT OPINION: ADHD BD may be associated with more severe symptoms, course, and worst outcome of both conditions. The frequent coexistence with alcohol and substance abuse may further complicate treatment management. Stimulants are the most effective medications for ADHD, but their use may be contraindicated in the presence of a comorbid drug abuse or in patients that simulate or exaggerate ADHD symptoms in order to obtain stimulants for diversion or abuse. ATX may be effective in the treatment of ADHD symptoms in BD patients, with a modestly increased risk of (hypo)manic switches and destabilization of the mood disorder when utilized in association with mood stabilizers. In the majority of the cases, a hierarchical approach is desirable, with mood stabilization preceding the treatment of ADHD symptoms. Although systematic trials on the use of stimulants and ATX in ADHD-BD comorbidity in adulthood are necessary, both treatments should be considered possible options to be carefully evaluated once the patient has been stabilized. PMID- 26364897 TI - Rasagiline for the treatment of Parkinson's disease: an update. AB - INTRODUCTION: Rasagiline is a potent, selective, irreversible Monoamine Oxidase-B (MAO-B) inhibitor, developed to prolong the action of dopamine in the brain. It has been demonstrated that rasagiline can improve motor and some non-motor symptoms (NMS) in both early and advanced Parkinson's disease (PD) patients, and it also exhibits neuroprotective and antiapoptotic properties. AREAS COVERED: The objective of this review, performed by a Medline search on the most recent papers investigating the therapeutic effects of rasagiline, is to describe the role of rasagiline in the schedule of treatment of early and advanced PD patients. It will then focus on its role in treating NMS, fatigue, early morning off and cognitive decline, which heavily affect quality of life for PD patients. EXPERT OPINION: Rasagiline is an efficacious, well-tolerated, easy to use drug. The drug has been extensively studied and has proven its efficacy in monotherapy and in combination with any other antiparkinsonian therapy. It proved to be efficacious in reducing 'off' time and in improving early morning 'off' but also some NMS, thus enhancing the therapeutic approach to PD. PMID- 26364898 TI - Eltrombopag for treatment of thrombocytopenia-associated disorders. AB - INTRODUCTION: Eltrombopag is an orally bioavailable, non-peptide thrombopoietin receptor agonist capable of stimulating platelet production through the differentiation of CD34+ hematopoietic progenitor cells into committed CD41+ megakaryocyte precursors and proliferation of megakaryocyte progenitor cells. AREAS COVERED: This drug has been tested in several clinical trials in adult patients with chronic immune thrombocytopenia (ITP), demonstrating the ability of the drug to reduce the burden of thrombocytopenia and its associated side effects. Two multicenter trials on eltrombopag in chronic ITP of childhood have been recently completed, showing that the drug is effective also in pediatric patients. Recent studies have suggested a potential role of eltrombopag in the treatment of thrombocytopenia associated with hepatitis-C virus infection. These studies have documented that adjunct treatment with eltrombopag can help avoid either dose reductions or withdrawal of pegylated interferon due to development of thrombocytopenia. Eltrombopag has shown efficacy also in patients with acquired severe aplastic anemia and myelodysplastic syndromes. EXPERT OPINION: Eltrombopag plays an important therapeutic role in many different conditions characterized by persistent thrombocytopenia. A more comprehensive definition of both long-term safety and benefits deriving from the use of eltrombopag will be obtained through prolonged observation of patients already enrolled in the different studies conducted so far and from future prospective controlled trials. PMID- 26364899 TI - Erratum. Correction to: The pharmacokinetics and clinical efficacy of AVP-825: a potential advancement for acute treatment of migraine. PMID- 26364900 TI - Investigation of the maternal and cord plasma levels of IL-1 beta, TNF-alpha and VEGF in early membrane rupture. AB - OBJECTIVE: Recent studies indicate a relationship between early membrane rupture (EMR) and proinflammatory cytokines like tumor necrosis factor (TNF) and interleukin (IL) and angiogenic factors like vascular endothelial growth factor (VEGF). In this study, we aimed to investigate the relationship between EMR and maternal and cord blood plasma levels of TNF-alpha, IL-1 beta and VEGF. METHODS: This prospective, cross-sectional study was conducted with 85 pregnant women. The patients were divided into four groups as Group I (term EMR group, n = 21), Group II (preterm EMR group, n = 23), Group III (preterm non-EMR group, n = 19) and Group IV (term non-EMR group, n = 22). Plasma levels were assayed with ELISA method. RESULTS: IL-1 beta levels were significantly lower, but TNF-alpha levels were significantly higher in maternal and cord plasma of EMR participants compared to non-EMR participants. There was no significant difference for VEGF levels. Cord plasma TNF-alpha levels were significantly higher than maternal plasma levels in EMR participants and cord plasma. VEGF levels were significantly higher than maternal levels in all participants. CONCLUSIONS: Higher TNF-alpha levels in our EMR participants indicate an inflammatory process during EMR. Higher cord plasma VEGF levels may point out placental or fetal production. Further studies conducted with expanded populations are needed to discuss our results. PMID- 26364901 TI - Report of a patient with a constitutional missense mutation in SMARCB1, Coffin Siris phenotype, and schwannomatosis. AB - We report a patient with a constitutional missense mutation in SMARCB1, Coffin Siris Syndrome (CSS), and schwannomatosis. CSS is a rare congenital syndrome with characteristic clinical findings. This thirty-three-year-old man was diagnosed early in life with the constellation of moderate intellectual disability, hypotonia, mild microcephaly, coarse facies, wide mouth with full lips, hypoplasia of the digits, and general hirsutism. At age 26, he was found to have schwannomatosis after presenting with acute spinal cord compression. Blood and tissue analysis of multiple subsequent schwannoma resections revealed a germline missense mutation of SMARCB1, acquired loss of 22q including SMARCB1 and NF2 and mutation of the remaining NF2 wild-type allele-thus completing the four-hit, three-event mechanism associated with schwannomatosis. Variations in five genes have been associated with the Coffin-Siris phenotype: ARID1A, ARID1B, SMARCA4, SMARCB1, and SMARCE1. Of these genes, SMARCB1 has a well-established association with schwannomatosis and malignancy. This is the first report of a patient with a constitutional missense mutation of SMARCB1 resulting in CSS and subsequent development of schwannomatosis. This finding demonstrates that a SMARCB1 mutation may be the initial "hit" (constitutional) for a genetic disorder with subsequent risk of developing schwannomas and other malignancies, and raises the possibility that other patients with switch/sucrose non-fermenting (SWI/SNF) mutations may be at increased risk for tumors. PMID- 26364902 TI - A direct catalytic ring expansion approach to o-fluoronaphthols and o/p fluorophenols from indanones and 2-cyclopentenones. AB - A direct method for the synthesis of o-fluoronaphthols and o/p-fluorophenols has been developed by a catalytic ring expansion of indanones and 2-cyclopentenones, in which TMSCF2Br was used as a unique :CF2 source, a TMS transfer agent, as well as the Br(-) and F(-) releaser for the enolization, difluorocyclopropanation, desilylation, ring opening, defluorination, and aromatization sequence. PMID- 26364904 TI - Radiographic Evaluations of Revision Total Knee Arthroplasty: A Plea for Uniform Assessments. AB - Thorough radiographic evaluation is necessary for perioperative assessments in revision total knee arthroplasty. There has been a large degree of variability in reporting these findings within the peer-reviewed literature. Our purpose was to evaluate studies that radiographically assessed alignment in the coronal and sagittal plane, patella alignment and thickness, presence and characterization of implant interface, and radiolucency. Secondly, we reviewed studies using a standardized reporting system to evaluate radiographic findings (the Knee Society Roentgenographic Evaluation and Scoring System) and the number of times it was referenced. Only 62% of studies evaluated all radiographic parameters, 57% to 91% assessed each metric, and 55% used standardized reporting systems. This emphasizes the need for a uniform evaluation method to ensure consistent radiographic assessment and optimal standard of care. PMID- 26364903 TI - RNA regulatory networks diversified through curvature of the PUF protein scaffold. AB - Proteins bind and control mRNAs, directing their localization, translation and stability. Members of the PUF family of RNA-binding proteins control multiple mRNAs in a single cell, and play key roles in development, stem cell maintenance and memory formation. Here we identified the mRNA targets of a S. cerevisiae PUF protein, Puf5p, by ultraviolet-crosslinking-affinity purification and high throughput sequencing (HITS-CLIP). The binding sites recognized by Puf5p are diverse, with variable spacer lengths between two specific sequences. Each length of site correlates with a distinct biological function. Crystal structures of Puf5p-RNA complexes reveal that the protein scaffold presents an exceptionally flat and extended interaction surface relative to other PUF proteins. In complexes with RNAs of different lengths, the protein is unchanged. A single PUF protein repeat is sufficient to induce broadening of specificity. Changes in protein architecture, such as alterations in curvature, may lead to evolution of mRNA regulatory networks. PMID- 26364905 TI - Bronchiolitis of Infancy Discharge Study (BIDS): a multicentre, parallel-group, double-blind, randomised controlled, equivalence trial with economic evaluation. AB - BACKGROUND: There are no randomised trials of peripheral capillary oxygen saturation (SpO2) targets in acute respiratory infection. Two national guidelines recommended different targets for the management of acute viral bronchiolitis. OBJECTIVES: To compare the American Academy of Pediatrics guideline target of SpO2 >= 90% with the Scottish Intercollegiate Guidelines Network target of SpO2 >= 94%. DESIGN: A multicentre, parallel-group, double-blind, randomised controlled, equivalence trial with economic evaluation. SETTING: Eight paediatric hospital departments in the UK. PARTICIPANTS: Infants > 6 weeks and <= 12 months of age (corrected for prematurity) with physician-diagnosed bronchiolitis admitted to hospital from a paediatric emergency assessment area. Follow-up for 6 months by standardised telephone contacts. INTERVENTION: Infants were randomised to a target oxygen saturation of >= 94% (standard care) or >= 90% (modified care) displayed by a pulse saturation oximeter (Masimo Corporation Limited, CA, USA). ROUTINE CARE: All infants received routine care in addition to the study intervention. Infants were eligible for discharge when they exhibited a SpO2 of >= 94% in room air for 4 hours including a period of sleep and were also feeding adequately (>= 75% usual volume). PRIMARY OUTCOME: A total of 615 infants were recruited, of whom 308 were allocated to the standard care group and 307 to the modified care group. The primary outcome was time to cough resolution. There was equivalence at the prespecified variance of +/- 2 days [time to cough resolution: standard care group, 15 days; modified care group, 15 days; median difference 1 day (benefit modified), 95% confidence interval (CI) -1 to 2 days]. SECONDARY RESULTS: Return to adequate feeding occurred sooner in infants in the modified care group than in those in the standard care group (19.5 vs. 24.1 hours). This difference was non-equivalent [median difference 2.7 hours (95% CI -0.3 to 7.0 hours) versus prespecified +/- 4 hours; post-hoc hazard ratio 1.22 (95% CI 1.04 to 1.44 (p-value = 0.015)]. Parent perspective of the time taken to return to normal was not equivalent, being 12 days in the standard care group compared with 11 days in the modified care group [median difference 1.0 day (95% CI 0.0 to 3.0 days) versus prespecified +/- 2 days; post-hoc hazard ratio 1.19 (95% CI 1.00 to 1.41); p-value = 0.043]. At 28 days, SpO2 was equivalent [mean difference 0.11% (95% CI -0.35% to 0.57%), within the 1% prespecified]. The modified care group (55.6%) required oxygen less than the standard care group (73.1%), and for a shorter period (5.7 hours vs. 27.6 hours). Infants in the modified care group were fit for discharge (30.2 hours vs. 44.2 hours, hazard ratio 1.46, 95% CI 1.23 to 1.73; p-value < 0.001) and were discharged (40.9 hours vs. 50.9 hours; hazard ratio 1.28, 95% CI 1.06 to 1.50; p-value < 0.003) sooner than those in the standard care group. There were 35 serious adverse events in the standard care group, compared with 25 in the modified care group. Eight infants in the standard care group and 12 in the modified care group were admitted to a high-dependency unit. By 28 days, 23 infants had been readmitted to hospital in the standard care group and 12 infants in the modified care group. Parents of infants in the modified care group did not experience higher levels of anxiety and, by 14 days, had lost 28% fewer hours to usual activities. NHS costs were L290 lower in the modified care group than in the standard care group, with additional societal costs also being lower in the modified care group. CONCLUSIONS: Management of infants to a SpO2 target of >= 90% is as clinically effective as >= 94%, gives rise to no additional safety concerns, and appears to be cost-effective. Future work could focus on the safety and effectiveness of using intermittent oxygen saturation monitoring in secondary care, and to consider what are safe and effective oxygen saturation targets for children with bronchiolitis managed in primary care. TRIAL REGISTRATION: This trial is registered as ISRCTN28405428. FUNDING: This project was funded by the NIHR Health Technology Assessment programme. Masimo Corporation Limited, CA, USA, kindly provided oxygen saturation monitors with standard and altered algorithms. PMID- 26364906 TI - Disinfection by-products effect on swimmers oxidative stress and respiratory damage. AB - Disinfection by-products (DBPs) are generated through the reaction of chlorine with organic and inorganic matter in indoor swimming pools. Different DBPs are present in indoor swimming pools. This study evaluated the effects of different chlorinated formations in oxidative stress and lung damage in 20 swimmers after 40 min of aerobic swimming in 3 indoor pools with different characteristics. Biological samples were collected to measure lung damage (serum-surfactant associated proteins A and B), oxidative stress parameters (plasma protein carbonylation and malondialdehyde, and whole-blood glutathione oxidation), and swimming exertion values (blood lactate) before and after exercise. Free chlorine and combined chlorine in water, and chlorine in air samples were determined in all the swimming pools. Chlorination as disinfection treatment led to the formation of chloramines in water samples, mainly mono- and dichloramine. However, free chlorine was the predominate species in ultraviolet-treated swimming pool. Levels of total chlorine increased as a function of the swimming activity in chlorinated swimming pools. The lower quality of the installation resulted in a higher content of total chlorine, especially in air samples, and therefore a higher exposure of the swimmer to DBPs. However, the concentration level of chlorinated DBPs did not result in significant variation in serum surfactant-associated proteins A and oxidative stress parameters in swimmers. In conclusion, the quality of the installation affected the DBPs concentration; however, it did not lead to lung epithelial damage and oxidative stress parameters in swimmers. PMID- 26364907 TI - Psychometric Properties of the Montgomery-Asberg Depression Rating Scale in Severely Obese Patients. AB - Obesity is a chronic condition worldwide and has frequent association with major depression. The Montgomery-Asberg Depression Rating Scale (MADRS) was applied to obese patients in order to detect briefly and systematically depressive symptoms. The objectives were: to estimate the reliability of the MADRS and to investigate the criterion validity of MADRS. The best cut-off point to detect depressive symptoms was determined in comparison with the Structured Clinical Interview for DSM-IV Axis I Diagnosis (SCID-I). The sample was recruited consecutively from the waiting list of a bariatric surgery service of the university clinic. Trained clinical psychologists applied the assessment instruments. The final sample was comprised of 374 class III obese adults (women 79.9 %, mean age 43.3 years [SD 11.6], mean body mass index 47.0 kg/m2 [SD 7.1]). The mean total score of the MADRS was 7.73 (SD 11.33) for the total sample, with a Cronbach's alpha coefficient of .93. Women presented higher mean score than men (8.08 versus 6.33; p = .23). The best cut-off point was 13/14 in accordance with the Receiver Operating Characteristics (ROC) curve analysis, yielding a sensitivity of .81 and specificity of .85. The overall ability to discriminate depression according to area under the curve was .87. The results showed that the MADRS is a reliable and valid scale to detect depressive symptoms among patients seeking treatment in preoperative period, displaying adequate psychometric properties. PMID- 26364908 TI - Temporal trends and factors associated with pediatric hospitalizations with respiratory infection. AB - OBJECTIVES: Asthma is the leading cause of emergency room visits in children, and those with asthma tend to suffer from more severe consequences of respiratory tract infections. The aims of this study were among children who required hospitalization, compare differences between those admitted with or without respiratory infection, describe changes in yearly proportion of asthma among the children admitted with a respiratory infection in New York City from 2006 to 2012 and ascertain how asthma affected the average length of hospital stay for those with respiratory infection. METHODS: We conducted an historical prospective study using data obtained from multiple electronic sources of patients discharged from a 200-bed pediatric hospital in a major metropolitan healthcare system between 2006 and 2012. Patient characteristics were obtained from electronic health records and billing codes. RESULTS: Among 83,348 patient discharges, there were 5057 (6.1%) with a respiratory infection. In the multivariable model, children with the following characteristics were significantly more likely to be admitted with a respiratory infection as compared with other diagnoses: asthma [odds ratio (OR) 4.68 (95% confidence limits (CL): 4.31, 5.08], male sex [OR:1.11 (1.05, 1.18)], prior hospitalization [OR: 3.65 (3.43, 3.89)], renal failure [(OR: 2.14 (1.70, 2.70)] and Medicaid coverage [OR: 1.93 (1.81, 2.05)]. Children aged >= 5 years (OR: 0.44 (0.41, 0.47) and those with diabetes (OR: 0.32 (0.21, 0.51) were less likely to be admitted with a respiratory infection. Hospitalized patients with respiratory infection and asthma, identified by ICD-9 codes, had significantly shorter lengths of stay than patients without asthma, 5.3 and 9.0 days, respectively, p < 0.001. Asthma in patients admitted with a respiratory infection increased from 19.2% in 2006 to 28.2% in 2012, peaking at 34.1% in 2010 (p < 0.001). CONCLUSION: This study suggests that asthma is a significant risk factor for hospitalization of children with respiratory infection, and suggests that the prevalence of asthma is increasing over time among children hospitalized with respiratory infection in this urban setting. PMID- 26364909 TI - Criteria led discharge reduces length of hospital stay for children with acute asthma. PMID- 26364910 TI - Stimulation of 5-HT7 receptor during adolescence determines its persistent upregulation in adult rat forebrain areas. AB - Brain serotonin 7 (5-HT7) receptors play an important functional role in learning and memory, in regulation of mood and motivation, and for circadian rhythms. Recently, we have studied the modulatory effects of a developmental exposure (under subchronic regimen) in rats with LP-211, a brain-penetrant and selective 5 HT7 receptor agonist. We aimed at further deciphering long-term sequelae into adulthood. LP-211 (0.250 mg/kg i.p., once/day) was administered for 5 days during the adolescent phase (postnatal days 43-45 to 47-49). When adult (postnatal days >70), forebrain areas were obtained for ex vivo immunohistochemistry, whose results prompted us to reconsider the brain connectivity maps presented in our previous study (Canese et al., Psycho-Pharmacol 2015;232:75-89.) Significant elevation in levels of 5-HT7 receptors were evidenced due to adolescent LP-211 exposure, in dorsal striatum (which also shows an increase of dopaminergic D2 auto-receptors) and-unexpectedly-in piriform cortex, with no changes in ventral striatum. We observed that functional connectivity from a seed on the right hippocampus was more extended than reported, also including the piriform cortex. As a whole, the cortical loop rearranged by adolescent LP-211 exposure consisted in a hippocampus receiving connections from piriform cortex and dorsal striatum, the latter both directly and through functional control over the 'extended amygdala'. Such results represent a starting point to explore neurophysiology of 5-HT7 receptors. Further investigation is warranted to develop therapies for sleep disorders, for impaired emotional and motivational regulation, for attentive and executive deficit. The 5-HT7 agonist LP-211 (0.250 mg/kg i.p., once/day) was administered for 5 days during adolescence (postnatal days 43-45 to 47-49) in rats. When adult (postnatal days >70), a significant elevation in levels of 5-HT7 receptors were evidenced in dorsal striatum and-unexpectedly-in piriform cortex. PMID- 26364911 TI - The Cl + O3 reaction: a detailed QCT simulation of molecular beam experiments. AB - We have studied in detail the dynamics of the Cl + O3 reaction in the 1-56 kcal mol(-1) collision energy range using quasi-classical trajectory (QCT) calculations on a recent potential energy surface (PES) [J. F. Castillo et al., Phys. Chem. Chem. Phys., 2011, 13, 8537]. The main goal of this work has been to assess the accuracy of the PES and the reliability of the QCT method by comparison with the existing crossed molecular beam results [J. Zhang and Y. T. Lee J. Phys. Chem. A, 1997, 101, 6485]. For this purpose, we have developed a methodology that allows us to determine the experimental observables in crossed molecular beam experiments (integral and differential cross sections, recoil velocity distributions, scattering angle-recoil velocity polar maps, etc.) as continuous functions of the collision energy. Using these distributions, raw experimental data in the laboratory frame (angular distributions and time-of flight spectra) have been simulated from first principles with the sole information on the instrumental parameters and taking into account the energy spread. A general good agreement with the experimental data has been found, thereby demonstrating the adequacy of the QCT method and the quality of the PES to describe the dynamics of this reaction at the level of resolution of the existing crossed beam experiments. Some features which are apparent in the differential cross sections have also been analysed in terms of the dynamics of the reaction and its evolution with the collision energy. PMID- 26364912 TI - Onychopapilloma manifesting longitudinal melanonychia: A mimic of subungual malignancy. PMID- 26364913 TI - The Mycobacterium tuberculosis PPE protein Rv1168c induces stronger B cell response than Rv0256c in active TB patients. AB - Tuberculosis (TB) caused by Mycobacterium tuberculosis is a serious global health problem and is responsible for millions of deaths every year. For effective control of this dreadful disease, it is necessary to diagnose TB cases at the initial stages of infection. The serodiagnosis of disease represents simple, rapid and inexpensive method that can be used at the primary health care levels. In this study we have compared sensitivity of two PPE proteins of M. tuberculosis, i.e., Rv0256c and Rv1168c for their use as serodiagnostic markers in active tuberculosis patients. Employing a standardized enzyme immunoassay with these PPE proteins as candidate antigens we were able to successfully discriminate the TB patients' sera from the BCG-vaccinated healthy controls. Further, we observed that Rv1168c displayed higher sensitivity in detecting extrapulmonary and smear negative pulmonary TB cases which are difficult to diagnose by available diagnostic methods. Overall the study highlights that Rv1168c can be used as a potential serodiagnostic marker for the diagnosis of active tuberculosis disease. PMID- 26364914 TI - The emotional maltreatment of children in domestically violent homes: Identifying gaps in education and addressing common misconceptions. The risk of harm to children in domestically violent homes mandates a well-coordinated response. PMID- 26364915 TI - Click Addition of a DNA Thread to the N-Termini of Peptides for Their Translocation through Solid-State Nanopores. AB - Foremost among the challenges facing single molecule sequencing of proteins by nanopores is the lack of a universal method for driving proteins or peptides into nanopores. In contrast to nucleic acids, the backbones of which are uniformly negatively charged nucleotides, proteins carry positive, negative and neutral side chains that are randomly distributed. Recombinant proteins carrying a negatively charged oligonucleotide or polypeptide at the C-termini can be translocated through a alpha-hemolysin (alpha-HL) nanopore, but the required genetic engineering limits the generality of these approaches. In this present study, we have developed a chemical approach for addition of a charged oligomer to peptides so that they can be translocated through nanopores. As an example, an oligonucleotide PolyT20 was tethered to peptides through first selectively functionalizing their N-termini with azide followed by a click reaction. The data show that the peptide-PolyT20 conjugates translocated through nanopores, whereas the unmodified peptides did not. Surprisingly, the conjugates with their peptides tethered at the 5'-end of PolyT20 passed the nanopores more rapidly than the PolyT20 alone. The PolyT20 also yielded a wider distribution of blockade currents. The same broad distribution was found for a conjugate with its peptide tethered at the 3'-end of PolyT20, suggesting that the larger blockades (and longer translocation times) are associated with events in which the 5'-end of the PolyT20 enters the pore first. PMID- 26364916 TI - Human fused NKG2D-IL-15 protein controls xenografted human gastric cancer through the recruitment and activation of NK cells. AB - Interleukin (IL)-15 plays an important role in natural killer (NK) and CD8+ T cell proliferation and function and is more effective than IL-2 for tumor immunotherapy. The trans-presentation of IL-15 by neighboring cells is more effective for NK cell activation than its soluble IL-15. In this study, the fusion protein dsNKG2D-IL-15, which consisted of two identical extracellular domains of human NKG2D coupled to human IL-15 via a linker, was engineered in Escherichia coli. DsNKG2D-IL-15 could efficiently bind to major histocompatibility complex class I chain-related protein A (MICA) of human tumor cells with the two NKG2D domains and trans-present IL-15 to NK or CD8+ T cells. We transplanted human gastric cancer (SGC-7901) cells into nude mice and mouse melanoma cells with ectopic expression of MICA (B16BL6-MICA) into C57BL/6 mice. Then, we studied the anti-tumor effects mediated by dsNKG2D-IL-15 in the two xenografted tumor models. Human dsNKG2D-IL-15 exhibited higher efficiency than IL 15 in suppressing gastric cancer growth. Exogenous human dsNKG2D-IL-15 was centrally distributed in the mouse tumor tissues based on in vivo live imaging. The frequencies of human CD56+ cells infiltrated into the tumor tissues following the injection of peripheral blood mononuclear cells into nude mice bearing human gastric cancer were significantly increased by human dsNKG2D-IL-15 treatment. Human dsNKG2D-IL-15 also delayed the growth of transplanted melanoma (B16BL6 MICA) by activating and recruiting mouse NK and CD8+ T cells. The anti-melanoma effect of human dsNKG2D-IL-15 in C57BL/6 mice was mostly decreased by the in vivo depletion of mouse NK cells. These data highlight the potential use of human dsNKG2D-IL-15 for tumor therapy.Cellular & Molecular Immunology advance online publication, 14 September 2015; doi:10.1038/cmi.2015.81. PMID- 26364917 TI - Screening and identification of mimotopes of the major shrimp allergen tropomyosin using one-bead-one-compound peptide libraries. AB - The one-bead-one-compound (OBOC) combinatorial peptide library is a powerful tool to identify ligand and receptor interactions. Here, we applied the OBOC library technology to identify mimotopes specific to the immunoglobulin E (IgE) epitopes of the major shellfish allergen tropomyosin. OBOC peptide libraries with 8-12 amino acid residues were screened with serum samples from patients with shellfish allergy for IgE mimotopes of tropomyosin. Twenty-five mimotopes were identified from the screening and their binding reactivity to tropomyosin-specific IgE was confirmed by peptide ELISA. These mimotopes could be divided into seven clusters based on sequence homology, and epitope mapping by EpiSearch of the clustered mimotopes was performed to characterize and confirm the validity of mimotopes. Five out of six of the predicted epitopes were found to overlap with previously identified epitopes of tropomyosin. To further confirm the mimicry potential of mimotopes, BALB/c mice were immunized with mimotopes conjugated to keyhole limpet hemocyanin and assayed for their capacity to induce tropomyosin-specific antibodies. BALB/c mice that received mimotope immunization were found to have an elevated level of tropomyosin-specific immunoglobulin G, but not mice that received an irrelevant mimotope. This study pioneers the successful application of the OBOC libraries using whole sera to screen and identify multiple shrimp allergen mimotopes and validates their mimicry potential using in vitro, in vivo, and in silico methods.Cellular & Molecular Immunology advance online publication, 14 september 2015; doi:10.1038/cmi.2015.83. PMID- 26364919 TI - The Chemical Record--A Historical Commentary. PMID- 26364918 TI - Genetic relationships among American donkey populations: insights into the process of colonization. AB - This study presents the first insights into the genetic diversity and structure of the American donkey metapopulation. The primary objectives were to detect the main structural features underlying variability among American donkey populations, identify boundaries between differentiated gene pools, and draw the main colonization pathways since the introduction of donkeys into America in the 15th century. A panel of 14 microsatellite markers was applied for genotyping 350 American donkeys from 13 countries. The genetic structure of this metapopulation was analysed using descriptive statistics and Bayesian model-based methods. These populations were then compared to a database containing information on 476 individuals from 11 European breeds to identify the most likely ancestral donor populations. Results showed the presence of two distinct genetic pools, with confluence of the two in Colombia. The southern pool showed a unique genetic signature subsequent to an older founder event, but lacked any significant influence of modern gene flow from Europe. The northern pool, conversely, may have retained more ancestral polymorphisms and/or have experienced modern gene flow from Spanish breeds. The Andalusian and, to a lesser extent, the Catalan breeds have left a more pronounced footprint in some of the American donkey populations analysed. PMID- 26364920 TI - Shape control of mesoporous silica nanomaterials templated with dual cationic surfactants and their antibacterial activities. AB - Mesoporous silica nanomaterials of different shapes (film, platelet, sphere, rod) were synthesized simply by tuning the mole ratio of dual cationic surfactant templates, cetyltrimethylammonium bromide (CTAB) and tetrabutylammonium iodine (TBAI). The film showed the most potent antibacterial activity against mycobacteria. PMID- 26364921 TI - Chronic stress alters the dendritic morphology of callosal neurons and the acute glutamate stress response in the rat medial prefrontal cortex. AB - We have previously reported that interhemispheric regulation of medial prefrontal cortex (PFC)-mediated stress responses is subserved by glutamate (GLU)- containing callosal neurons. Evidence of chronic stress-induced dendritic and spine atrophy among PFC pyramidal neurons led us to examine how chronic restraint stress (CRS) might alter the apical dendritic morphology of callosal neurons and the acute GLU stress responses in the left versus right PFC. Morphometric analyses of retrogradely labeled, dye-filled PFC callosal neurons revealed hemisphere-specific CRS-induced dendritic retraction; whereas significant dendritic atrophy occurred primarily within the distal arbor of left PFC neurons, it was observed within both the proximal and distal arbor of right PFC neurons. Overall, CRS also significantly reduced spine densities in both hemispheres with the greatest loss occurring among left PFC neurons, mostly at the distal extent of the arbor. While much of the overall decrease in dendritic spine density was accounted by the loss of thin spines, the density of mushroom-shaped spines, despite being fewer in number, was halved. Using microdialysis we found that, compared to controls, basal PFC GLU levels were significantly reduced in both hemispheres of CRS animals and that their GLU response to 30 min of tail-pinch stress was significantly prolonged in the left, but not the right PFC. Together, these findings show that a history of chronic stress alters the dendritic morphology and spine density of PFC callosal neurons and suggest a mechanism by which this might disrupt the interhemispheric regulation of PFC-mediated responses to subsequent stressors. PMID- 26364922 TI - Substituting cannabis for prescription drugs, alcohol and other substances among medical cannabis patients: The impact of contextual factors. AB - INTRODUCTION AND AIMS: Recent years have witnessed increased attention to how cannabis use impacts the use of other psychoactive substances. The present study examines the use of cannabis as a substitute for alcohol, illicit substances and prescription drugs among 473 adults who use cannabis for therapeutic purposes. DESIGN AND METHODS: The Cannabis Access for Medical Purposes Survey is a 414 question cross-sectional survey that was available to Canadian medical cannabis patients online and by hard copy in 2011 and 2012 to gather information on patient demographics, medical conditions and symptoms, patterns of medical cannabis use, cannabis substitution and barriers to access to medical cannabis. RESULTS: Substituting cannabis for one or more of alcohol, illicit drugs or prescription drugs was reported by 87% (n = 410) of respondents, with 80.3% reporting substitution for prescription drugs, 51.7% for alcohol, and 32.6% for illicit substances. Respondents who reported substituting cannabis for prescription drugs were more likely to report difficulty affording sufficient quantities of cannabis, and patients under 40 years of age were more likely to substitute cannabis for all three classes of substance than older patients. DISCUSSION AND CONCLUSIONS: The finding that cannabis was substituted for all three classes of substances suggests that the medical use of cannabis may play a harm reduction role in the context of use of these substances, and may have implications for abstinence-based substance use treatment approaches. Further research should seek to differentiate between biomedical substitution for prescription pharmaceuticals and psychoactive drug substitution, and to elucidate the mechanisms behind both. [Lucas P, Walsh Z, Crosby K, Callaway R, Belle-Isle L, Kay B, Capler R, Holtzman S. Substituting cannabis for prescription drugs, alcohol, and other substances among medical cannabis patients: The impact of contextual factors. Drug Alcohol Rev 2016;35:326-333]. PMID- 26364923 TI - Icariin, a major constituent of flavonoids from Epimedium brevicornum, protects against cognitive deficits induced by chronic brain hypoperfusion via its anti amyloidogenic effect in rats. AB - Chronic cerebral hypoperfusion is considered to be a pivotal contributing factor of cognitive impairments that occur in vascular dementia and Alzheimer's disease, and ideal drug treatment for these diseases is unavailable. Hence, this study was designed to investigate the protective effects of icariin, a major constituent of flavonoids from the Chinese medicinal herb Epimedium brevicornum, on cognitive impairments and neuronal morphological damage induced by permanent occlusion of bilateral common carotid arteries (BCCAO) in rats, and further explore the potential mechanisms. This study found that BCCAO could induce cognitive deficits and neuronal morphological damage, along with deposition of beta-amyloid (Abeta) in rat hippocampus. However, oral administration of icariin twice per day for 23days might attenuate cognitive deficits and neuronal morphological damage induced by BCCAO. Subsequently, icariin decreased the level of Abeta in rat hippocampus subjected to BCCAO. Administration of icariin reduced the expressions of amyloid precursor protein (APP), beta-secretase 1 (BACE1), and increased the expressions of insulin-degrading enzyme (IDE) and a disintegrin and metalloproteinase domain 10 (ADAM10) in rat hippocampus. Furthermore, icariin afforded beneficial actions in suppressing transforming growth factor-beta1 (TGF beta1) signaling via inhibition of Smad2/3 phosphorylation. In summary, icariin is effective in improving cognitive deficits and hippocampus morphological alterations subjected to BCCAO. This protection appears to be due to the decreased expressions of both APP and BACE1, and the increased expressions of both IDE and ADAM10, resulting in a decrease in the level of insoluble Abeta fragments in rat hippocampus. Inhibitions of TGF-beta1 signaling and Smad2/3 phosphorylation are involved in the course. PMID- 26364924 TI - Sodium selenite supplementation during pregnancy and lactation promotes anxiolysis and improves mnemonic performance in wistar rats' offspring. AB - Selenium is a micronutrient which is part of selenoprotein molecules and participates in a vast number of physiological roles and, among them,we have fetal and neonatal development. Therefore, the aimof this studywas to evaluate possible behavioral changes in offspring of female rats supplemented during pregnancy and lactation with sodium selenite. To address that, we treated two groups of female rats by saline or sodium selenite at a dose of 1mg/kg through oral route and performed neurochemical and behavioral tests. In the offspring, the thyroid profile and hippocampal neurochemistrywere evaluated. Behavioral testswere performed in pups both during childhood and adulthood. We found out that selenium (Se) supplementation increased serum levels of triiodothyronine (25%, p b 0.001) and thyroxine (18%, p b 0.05) and promoted a tryptophan hydroxylase 2 (TPH 2) expression decrease (17%, p b 0.01) and tyrosine hydroxylase (TH) expression increase (202%, p b 0.01) in the hippocampus. The cholinesterase activity was decreased (28%, p b 0.01) in Se supplemented rats, suggesting a neurochemical modulation in the hippocampal activity. During childhood, the Sesupplemented offspring had a reduction in anxiety-like behavior both in elevated plus maze test and in light-dark box test. In adulthood, Se treated pups had an increase in the locomotor activity (36%, p b 0.05) and in rearing episodes (77%, p b 0.001) in the open field test, while in the elevated plus maze test they also exhibited an increase in the time spent in the open arms (243%, p b 0.01). For the object recognition test, Se-treated offspring showed increase in the absolute (230.16%, p b 0.05) and relative index discrimination (234%, p b 0.05). These results demonstrate that maternal supplementation by sodium selenite promoted psychobiological changes both during childhood and adulthood. Therefore, the behavioral profile observed possibly can be explained by neurochemical changes induced by thyroid hormones during the critical period of the central nervous system ontogeny. PMID- 26364925 TI - Peptide-Graphene Interactions Enhance the Mechanical Properties of Silk Fibroin. AB - Studies reveal that biomolecules can form intriguing molecular structures with fascinating functionalities upon interaction with graphene. Then, interesting questions arise. How does silk fibroin interact with graphene? Does such interaction lead to an enhancement in its mechanical properties? In this study, using large-scale molecular dynamics simulations, we first examine the interaction of graphene with several typical peptide structures of silk fibroin extracted from different domains of silk fibroin, including pure amorphous (P1), pure crystalline (P2), a segment from N-terminal (P3), and a combined amorphous and crystalline segment (P4), aiming to reveal their structural modifications. Our study shows that graphene can have intriguing influences on the structures formed by the peptides with sequences representing different domains of silk fibroin. In general, for protein domains with stable structure and strong intramolecular interaction (e.g., beta-sheets), graphene tends to compete with the intramolecular interactions and thus weaken the interchain interaction and reduce the contents of beta-sheets. For the silk domains with random or less ordered secondary structures and weak intramolecular interactions, graphene tends to enhance the stability of peptide structures; in particular, it increases the contents of helical structures. Thereafter, tensile simulations were further performed on the representative peptides to investigate how such structure modifications affect their mechanical properties. It was found that the strength and resilience of the peptides are enhanced through their interaction with graphene. The present work reveals interesting insights into the interactions between silk peptides and graphene, and contributes in the efforts to enhance the mechanical properties of silk fibroin. PMID- 26364926 TI - Fluorous 'ponytails' lead to strong gelators showing thermally induced structure evolution. AB - Appending perfluoroalkyl substituents to bis(urea) gelators results in significantly decreased inter-chain interactions with markedly thinner fibres and hence more cross-linked and more transparent gels with potential applications in the crystallisation of fluorinated pharmaceuticals. Gel structure has been probed by detailed SANS measurements which indicate a surprising structure evolution on thermal cycling, not seen for hydrocarbon analogues. The SANS data are complemented by the single crystal X-ray structure of one fluorinated gelator. PMID- 26364927 TI - Placental passage of olomoucine II, but not purvalanol A, is affected by p glycoprotein (ABCB1), breast cancer resistance protein (ABCG2) and multidrug resistance-associated proteins (ABCCs). AB - 1. Purine cyclin-dependent kinase inhibitors have recently been recognised as promising candidates for the treatment of various cancers. While pharmacodynamic properties of these compounds are relatively well understood, their pharmacokinetics including possible interactions with placental transport systems have not been characterised to date. 2. In this study, we investigated transplacental passage of olomoucine II and purvalanol A in rat focusing on possible role of p-glycoprotein (ABCB1), breast cancer resistance protein (ABCG2) and/or multidrug resistance-associated proteins (ABCCs). Employing the in situ method of dually perfused rat term placenta, we demonstrate transplacental passage of both olomoucine II and purvalanol A against the concentration gradient in foetus-to-mother direction. Using several ATP-binding cassette (ABC) drug transporter inhibitors, we confirm the participation of ABCB1, ABCG2 and ABCCs transporters in the placental passage of olomoucine II, but not purvalanol A. 3. Transplacental passage of olomoucine II and purvalanol A from mother to foetus is significantly reduced by active transporters, restricting thereby foetal exposure and providing protection against harmful effects of these xenobiotics. Importantly, we demonstrate that in spite of their considerable structural similarity, the two molecules utilise distinct placental transport systems. These facts should be kept in mind when introducing these prospective anticancer candidates and/or their analogues into the clinical area. PMID- 26364928 TI - KDM4/JMJD2 Histone Demethylase Inhibitors Block Prostate Tumor Growth by Suppressing the Expression of AR and BMYB-Regulated Genes. AB - Histone lysine demethylase KDM4/JMJD2s are overexpressed in many human tumors including prostate cancer (PCa). KDM4s are co-activators of androgen receptor (AR) and are thus potential therapeutic targets. Yet to date few KDM4 inhibitors that have anti-prostate tumor activity in vivo have been developed. Here, we report the anti-tumor growth effect and molecular mechanisms of three novel KDM4 inhibitors (A1, I9, and B3). These inhibitors repressed the transcription of both AR and BMYB-regulated genes. Compound B3 is highly selective for a variety of cancer cell lines including PC3 cells that lack AR. B3 inhibited the in vivo growth of tumors derived from PC3 cells and ex vivo human PCa explants. We identified a novel mechanism by which KDM4B activates the transcription of Polo like kinase 1 (PLK1). B3 blocked the binding of KDM4B to the PLK1 promoter. Our studies suggest a potential mechanism-based therapeutic strategy for PCa and tumors with elevated KDM4B/PLK1 expression. PMID- 26364930 TI - Disassembly of a Medial Transenvelope Structure by Antibiotics during Intracellular Division. AB - Chlamydiales possess a minimal but functional peptidoglycan precursor biosynthetic and remodeling pathway involved in the assembly of the division septum by an atypical cytokinetic machine and cryptic or modified peptidoglycan like structure (PGLS). How this reduced cytokinetic machine collectively coordinates the invagination of the envelope has not yet been explored in Chlamydiales. In other Gram-negative bacteria, peptidoglycan provides anchor points that connect the outer membrane to the peptidoglycan during constriction using the Pal-Tol complex. Purifying PGLS and associated proteins from the chlamydial pathogen Waddlia chondrophila, we unearthed the Pal protein as a peptidoglycan-binding protein that localizes to the chlamydial division septum along with other components of the Pal-Tol complex. Together, our PGLS characterization and peptidoglycan-binding assays support the notion that diaminopimelic acid is an important determinant recruiting Pal to the division plane to coordinate the invagination of all envelope layers with the conserved Pal-Tol complex, even during osmotically protected intracellular growth. PMID- 26364929 TI - An Analysis of MIF Structural Features that Control Functional Activation of CD74. AB - For more than 15 years, the tautomerase active site of macrophage migration inhibitory factor (MIF) and its catalytic residue Pro1 have been being targeted for the development of therapeutics that block activation of its cell surface receptor, CD74. Neither the biological role of the MIF catalytic site nor the mechanistic details of CD74 activation are well understood. The inherently unstable structure of CD74 remains the biggest obstacle in structural studies with MIF for understanding the basis of CD74 activation. Using a novel approach, we elucidate the mechanistic details that control activation of CD74 by MIF surface residues and identify structural parameters of inhibitors that reduce CD74 biological activation. We also find that N-terminal mutants located deep in the catalytic site affect surface residues immediately outside the catalytic site, which are responsible for reduction of CD74 activation. PMID- 26364931 TI - Metabolic Enzyme Sulfotransferase 1A1 Is the Trigger for N-Benzyl Indole Carbinol Tumor Growth Suppression. AB - In an attempt to identify novel therapeutics and mechanisms to differentially kill tumor cells using phenotypic screening, we identified N-benzyl indole carbinols (N-BICs), synthetic analogs of the natural product indole-3-carbinol (I3C). To understand the mode of action for the molecules we employed Cancer Cell Line Encyclopedia viability profiling and correlative informatics analysis to identify and ultimately confirm the phase II metabolic enzyme sulfotransferase 1A1 (SULT1A1) as the essential factor for compound selectivity. Further studies demonstrate that SULT1A1 activates the N-BICs by rendering the compounds strong electrophiles which can alkylate cellular proteins and thereby induce cell death. This study demonstrates that the selectivity profile for N-BICs is through conversion by SULT1A1 from an inactive prodrug to an active species that induces cell death and tumor suppression. PMID- 26364933 TI - Exploration of Nonribosomal Peptide Families with an Automated Informatic Search Algorithm. AB - Microbial natural products are some of the most important pharmaceutical agents and possess unparalleled chemical diversity. Here we present an untargeted metabolomics algorithm that builds on our validated iSNAP platform to rapidly identify families of peptide natural products. By utilizing known or in silico dereplicated seed structures, this algorithm screens tandem mass spectrometry data to elaborate extensive molecular families within crude microbial culture extracts with high confidence and statistical significance. Analysis of peptide natural product producers revealed an abundance of unreported congeners, revealing one of the largest families of natural products described to date, as well as a novel variant with greater potency. These findings demonstrate the effectiveness of the iSNAP platform as an accurate tool for rapidly profiling large families of nonribosomal peptides. PMID- 26364935 TI - 2015 - A year of anniversaries. PMID- 26364932 TI - Structure and Inhibition of Microbiome beta-Glucuronidases Essential to the Alleviation of Cancer Drug Toxicity. AB - The selective inhibition of bacterial beta-glucuronidases was recently shown to alleviate drug-induced gastrointestinal toxicity in mice, including the damage caused by the widely used anticancer drug irinotecan. Here, we report crystal structures of representative beta-glucuronidases from the Firmicutes Streptococcus agalactiae and Clostridium perfringens and the Proteobacterium Escherichia coli, and the characterization of a beta-glucuronidase from the Bacteroidetes Bacteroides fragilis. While largely similar in structure, these enzymes exhibit marked differences in catalytic properties and propensities for inhibition, indicating that the microbiome maintains functional diversity in orthologous enzymes. Small changes in the structure of designed inhibitors can induce significant conformational changes in the beta-glucuronidase active site. Finally, we establish that beta-glucuronidase inhibition does not alter the serum pharmacokinetics of irinotecan or its metabolites in mice. Together, the data presented advance our in vitro and in vivo understanding of the microbial beta glucuronidases, a promising new set of targets for controlling drug-induced gastrointestinal toxicity. PMID- 26364936 TI - Recognizing the value of assistance dogs in society. AB - Assistance dogs are specially trained to undertake a variety of tasks to help individuals with disabilities. This review gives an overview of the different types of assistance dogs in the UK, including guide dogs, hearing dogs, mobility assistance dogs, service dogs and dual-purpose dogs. The literature describes many benefits of assistance dogs, including their impact on physical wellbeing and safety of their 'owners,' as well as on psychological wellbeing and social inclusion. The role of assistance dogs in society is widely recognized by the public, but is not currently acknowledged in government social policy. The current evidence on the benefits of assistance dogs is limited by the type and scale of current research. This article highlights the need for independent funding for high quality research to enable social care and policy makers to make evidence-based decisions on the value of assistance dogs to people with disabilities. PMID- 26364937 TI - Antioxidant enzymes activity, lipid peroxidation, oxidative damage in the testis and epididymis, and steroidogenesis in rats after co-exposure to atrazine and ethanol. AB - Concomitant alcohol use and exposure to xenobiotics can adversely affect gonadal functions. This study investigated the oxidative status of the testis and epididymis and steroidogenesis of rats co-exposed to ethanol (EtoH, 5 mg kg(-1) b.wt.) and atrazine (ATZ, 50, 100, 300 mg kg(-1) b.wt.) for 3 weeks. The activities of catalase, superoxide dismutase, glutathione peroxidase, as well as the concentrations of glutathione and malondialdehyde, as indicators of oxidative stress were measured in the homogenates of the testis and epididymis. Testosterone and cholesterol concentrations as well as 17beta-hydroxysteroid dehydrogenase (17beta-HSD) activity were assayed in the plasma and testis respectively. After the administration of EtoH alone, or in combination with different doses of ATZ, oxidative damage as evident by malondialdehyde level was not observed in both the testis and epididymis. The combine exposure group showed dose-dependent decrease in plasma testosterone and testis cholesterol level and increase in testis 17beta-HSD activity compared to the EtoH group. Furthermore, the testes and epididymis of the EtoH-exposed rats treated with high dose of ATZ had severe histopathological damage. Therefore, ATZ-exposed alcohol-treated rats have histological damage of the testis and epididymis and lower testosterone level than EtoH-treated rats. PMID- 26364938 TI - Echinacea complex--chemical view and anti-asthmatic profile. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Echinacea purpurea (L.) Moench is one of the mostly used herbs in the traditional medicine for the treatment of respiratory diseases. Modern interest in Echinacea is directed to its immunomodulatory activity. Recent studies have shown that secretion of asthma-related cytokines in the bronchial epithelial cells can be reversed by Echinacea preparations. AIM OF THE STUDY: To examine the pharmacodynamics profile of Echinacea active principles, a complex has been isolated from its flowers by alkaline extraction and has been tested using an animal model of allergic asthma. MATERIAL AND METHODS: The structural features of Echinacea purpurea complex was determined using chemical and spectroscopic methods. Allergic inflammation of the airways was induced by repetitive exposure of guinea pigs to ovalbumin. Echinacea complex was then administered 14 days in 50mg/kg b.w. daily dose perorally. Bronchodilatory effect was verified as decrease in the specific airway resistance (sRaw) in vivo and by reduced contraction amplitude (mN) of tracheal and pulmonary smooth muscle to cumulative concentrations of acetylcholine and histamine in vitro. The impact on mucociliary clearance evaluated measurement of ciliary beat frequency (CBF) in vitro using LabVIEWTM Software. Anti-inflammatory effect of Echinacea complex was verified by changes in exhaled NO levels and by Bio-Plex(r) assay of Th2 cytokine concentrations (IL-4, IL-5, IL-13 and TNF alpha) in serum and bronchoalveolar lavage fluid (BALF). RESULTS: Chemical and spectroscopic studies confirmed the presence of carbohydrates, phenolic compounds and proteins, as well as the dominance of rhamnogalacturonan and arabinogalactan moieties in Echinacea complex. The significant decrease in sRaw values and suppressed histamine and acetylcholine-induced contractile amplitude of isolated airways smooth muscle that were similar to effects of control drug salbutamol confirmed Echinacea complex bronchodilatory activity. The anti-inflammatory effect was comparable with that of control agent budesonide and was verified as significantly reduced exhaled NO levels and concentration of Th2 cytokines in serum and BALF. The values of CBF were changed only insignificantly on long-term administration of Echinacea complex suggested its minimal negative impact on mucociliary clearance. CONCLUSION: Pharmacodynamic studies have confirmed significant bronchodilatory and anti-inflammatory effects of Echinacea complex that was similar to effects of classic synthetic drugs. Thus, results provide a scientific basis for the application of this herb in traditional medicine as a supplementary treatment of allergic disorders of the airways, such as asthma. PMID- 26364939 TI - Anti-Helicobacter pylori activity of bioactive components isolated from Hericium erinaceus. AB - ETHNOPHARMACOLOGICAL RELEVANCE: The fungus Hericium erinaceus (Bull.) Pers is used in Chinese traditional medicine to treat symptoms related to gastric ulcers. Different extracts from the fungus were assessed for anti-Helicobacter pylori activity to investigate the antibacterial activity of the ethanol extracts from H. erinaceus and verify the traditional indication of use. MATERIALS AND METHODS: The fruiting bodies of H. erinaceus were concentrated with ethanol by HPD-100 macroporous resin and the whole extract was partitioned by petroleum ether and chloroform to afford fractions with using a silica gel column. Several pure compounds of petroleum ether extracts were obtained and analyzed using nuclear magnetic resonance (NMR). The activity of the extracts and fractions towards H. pylori was assessed by the microdilution assay and by the disk diffusion assay in vitro. From the most active fraction, two pure compounds were isolated and identified as the main components with anti-H. pylori activity from the fungus H. erinaceus. The cytotoxicity of these two compounds against the human erythroleu kemia cell line K562 was also evaluated. RESULTS: The crude ethanol extracts from the fungus H. erinaceus were inhibitory to H. pylori. The petroleum ether extracts (PE1s, PE2s) and the chloroform extracts (TEs) demonstrated strong inhibition to H. pylori. The inhibition of H. pylori was observed through an agar dilution test with minimal inhibition concentration (MIC) values from 400MUg/mL to 12.5ug/mL. Two pure compounds, 1-(5-chloro-2-hydroxyphenyl)-3-methyl-1 butanone and 2,5-bis(methoxycarbonyl)terephthalic acid were isolated from the petroleum ether fractions and identified using (1)H NMR and (13)C NMR spectra analysis. The MIC value for 1-(5-chloro-2-hydroxyphenyl)-3-methyl-1-butanone was 12.5-50ug/mL and the MIC value for 2,5-bis(methoxycarbonyl)terephthalic acid was 6.25-25ug/mL. Both two compounds showed weak cytotoxicity against K562 with IC50<200mM. CONCLUSIONS: This study revealed that the extracts from petroleum ether contribute to the anti-H. pylori activity. The compounds obtained from petroleum ether extracts, 1-(5-chloro-2-hydroxyphenyl)-3-methyl-1-butanone and 2,5-bis(methoxycarbonyl)terephthalic acid, inhibit the growth of H. pylori. PMID- 26364940 TI - Evidence of gastric ulcer healing activity of Maytenus robusta Reissek: In vitro and in vivo studies. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Maytenus robusta Reissek (Celastraceae) is traditionally used in Brazilian folk medicine to treat gastric ulcer, as a substitute for M. ilicifolia, which is almost extinct. The gastroprotective properties of M. robusta were demonstrated previously using only preventive approaches, such as acute gastric ulcer models. However, the healing effect of M. robusta in gastric ulcers remains unclear. AIM OF THE STUDY: The current study was carried out to investigate the healing effectiveness of M. robusta hydroalcoholic extract (HEMR) from aerial parts in the acetic acid-induced chronic ulcer model and to determine its effect on cell proliferation, scavenging free radicals, and inflammatory and oxidative damage. MATERIAL AND METHODS: To evaluate the healing properties of HEMR in vivo, chronic gastric ulcer was induced in rats by 80% acid acetic. Next, different groups of animals (n=6) were treated orally with vehicle (water plus 1% tween, 1 ml/kg), omeprazole (20mg/kg), or HEMR (1-10mg/kg), twice daily for 7 days. At the end of the treatment, the total ulcer area (mm(2)) was measured and a sample of gastric tissue was taken for histological and histochemical analysis. Evaluation of GSH and LOOH levels, GST, SOD, CAT and MPO activity was also performed at the site of the lesion. In parallel, radical scavenging activity, cytoprotective effect, and cell proliferation activity in fibroblasts (L929 cells) were determined by in vitro trials. The antisecretory properties were evaluated using the pylorus ligature model in rats, and the anti-Helicobacter pylori activity was determined in vitro. Acute toxicity was evaluated by relative organ weight and biochemical parameters in serum. The prokinetic properties were also evaluated in mice. RESULTS: Oral administration of HEMR (10mg/kg) reduced the gastric ulcer area by 53%, compared to the vehicle group (120.0 +/- 8.3mm(2)), the regeneration of gastric mucosa was evidenced in histological analysis. Moreover, HEMR treatment increased gastric mucin content and reduced oxidative stress and inflammatory parameters at the site of the ulcer. In vitro, HEMR (1-1000 ug/ml) was able to scavenge free radical DPPH and promote cytoprotection against H2O2 in fibroblasts at 0.1-100 ug/ml. Moreover, HEMR healing properties also were confirmed by enhancement of proliferation and coverage of scratched wounds in fibroblast monolayer. However, HEMR (10mg/kg) by the intraduodenal route did not promote changes in volume, pH, total acidity or pepsin activity in the pylorus ligature model, and HEMR up to 2000 ug/ml also did not present considerable activity against H. pylori. In relation to gastrointestinal motility, HEMR (10mg/kg, p.o) did not provoke alterations. It is also important to mention that oral administration of HEMR did not produce any sign of acute toxicity in animals. CONCLUSIONS: The data here obtained show that M. robusta has evident ulcer healing potential, mainly through the strengthening of protective factors of gastric mucosa, such as mucus layer, antioxidant defenses and cell proliferation. Taking into account the advantages of cultivation and harvesting of M. robusta compared to M. ilicifolia, and the evidence presented here, it is plausible to conclude that hydroalcoholic extract obtained from aerial parts of M. robusta is an interesting source for the development of a phytotherapeutic formulation to treat gastric ulcer. PMID- 26364941 TI - Visceral fat enhances blood pressure reactivity to physical but not mental challenges in male adolescents. AB - BACKGROUND: Excess visceral fat is a major risk factor for hypertension. Enhanced blood pressure (BP) reactivity and delayed BP recovery from physical and mental challenges predict future hypertension. OBJECTIVES: Determine whether visceral fat is associated with higher BP reactivity and delayed BP recovery from physical and mental challenges during adolescence. METHODS: In a community-based sample of 283 male and 308 female adolescents, we measured visceral fat with magnetic resonance imaging, total body fat with bioimpedance, and beat-by-beat BP with a Finometer at rest and during physical (10-min standing) and mental (2-min math stress) challenges. RESULTS: Males vs. females showed greater BP reactivity and no differences in BP recovery from either type of challenges. Visceral fat was positively associated with BP reactivity to standing up only and in males only (+8.4 +/- 3.6 mmHg per 1 log cm(3) of visceral fat, P = 0.008), and this association was independent of total body fat. No association was seen between visceral fat and BP recovery from either type of challenge in either sex. All these associations were independent of age, puberty stage, height and initial BP. CONCLUSIONS: Adolescent males vs. females demonstrate greater BP reactivity but similar BP recovery from physical and mental challenges. Excess visceral fat enhances BP reactivity to physical but not mental challenges in males only. PMID- 26364942 TI - Progress in the development of fatty acid synthase inhibitors as anticancer targets. AB - Fatty acid synthase (E.C. 2.3.1.85; FASN) is a multifunctional enzyme system that catalyzes the formation of fatty acids from acetyl-CoA, malonyl-CoA, and NADPH and plays a central role in lipid biosynthesis. Two classes of FASN exist: FASN I in animals and fungi, and FASN II in plants and prokaryotes. Animal FASN I is a homodimeric protein found in the cytosol of lipogenic tissues such as the liver and brain. Many human carcinomas exhibit elevated levels of FASN I, though the benefit to cancer cells is still unclear. Inhibition of FASN I selectively effects apoptosis in cancer cells, and the role of FASN I in chemotherapy is a growing area of research with the use of natural products and small molecule inhibitors. PMID- 26364943 TI - Development of 4-methoxy-7-nitroindolinyl (MNI)-caged auxins which are extremely stable in planta. AB - Phytohormone auxin is a master regulator in plant growth and development. Regulation of cellular auxin level plays a central role in plant development. Auxin polar transport system modulates an auxin gradient that determines plant developmental process in response to environmental conditions and developmental programs. Photolabile caged auxins allow optical control of artificial auxin gradients at cellular resolution. Especially, two-photon uncaging system achieves high spatiotemporal control of photolysis reaction at two-photon cross-section. However, the development of caged versions of auxin has been limited by the instability of the caged auxins to higher plant metabolic activities. Here, we describe the synthesis and application of highly stable caged auxins, 4-methoxy-7 nitroindolinyl (MNI)-caged auxins. Natural auxin, indole 3-acetic acid, and two synthetic auxins, 1-NAA and 2,4-D were caged by MNI caging group. MNI-caged auxins showed a high stability in planta and a rapid release the original auxin when photolyzed. We demonstrated that optical control of auxin-responsive gene expression and auxin-related physiological responses by using MNI-caged auxins. We anticipate that MNI-caged auxins will be an effective tool for high-resolution control of endogenous auxin level. PMID- 26364944 TI - Synthesis and anticancer activities of novel 8-azapurine carbocyclic nucleoside hydrazones. AB - A series of novel 8-azapurine carbocyclic nucleoside hydrazones were synthesized through a useful procedure starting from amino alcohol and pyrimido dichloride. All the products were characterized by (1)H NMR, (13)C NMR and HRMS spectral analysis and the stereochemical structure of key intermediate was also confirmed by a single crystal X-ray diffraction crystallographic analysis. Moreover, the anticancer activities were evaluated in vitro against human liver cancer Huh-7 cell line and human breast cancer A549 cell line. PMID- 26364945 TI - Discovery of benzothiazine derivatives as novel, orally-active anti-epileptic drug candidates with broad anticonvulsant effect. AB - In order to develop novel anti-epileptic drugs that are effective for both general and partial seizure, we conducted in vivo screening of our chemical library in the mice MES and sc-PTZ models and found the benzothiazine 1 as lead compound. Optimization of this compound led to the discovery of compound 7b, which showed potent anticonvulsant effect in the MES, scPTZ and rat amygdala kindling models. Since the chemical structure of 7b is different from that of any existing AED, it is suggested that 7b may have unique mechanism of action for relieving both partial and generalized epilepsy. PMID- 26364946 TI - Anemia of chronic kidney disease. PMID- 26364947 TI - Autosomal dominant polycystic kidney disease. PMID- 26364948 TI - General versus spinal anaesthesia and postoperative delirium in an orthogeriatric population. AB - AIM: Postoperative delirium is common among elderly hip surgery patients. We aimed to pragmatically evaluate whether type of anaesthesia influenced postoperative delirium in an orthogeriatric population following hip fracture. METHOD: This observational study comprises prospectively collected data on hip fracture patients admitted between October 2010 and November 2011. Delirium was diagnosed clinically by geriatricians. RESULTS: Of the 344 patients admitted, seven managed conservatively and 19 with incomplete data were excluded; 318 patients were analysed. Average age was 81.6 (SD 9.8) years; 28% were men and 167 (53%) were administered general anaesthesia. Mean length of stay was 18 (SD 9.4) days. Overall, 172 patients (54%) experienced delirium. There was no apparent difference in postoperative delirium by anaesthetic type (88 vs 84, P = 0.15). CONCLUSION: Delirium was common in both general and spinal anaesthetic patients. Further randomised controlled trials would be required to determine whether anaesthesia type influenced delirium rates. PMID- 26364949 TI - Selective recognition of D-tryptophan from d/l-tryptophan mixtures in the presence of Cu(II) by electropolymerized L-lysine film. AB - Selective recognition of D-tryptophan (D-Trp) in the presence of Cu(II) was investigated at poly-L-lysine (p-l-Lys) film using electrochemical impedance spectroscopy (EIS) and differential pulse voltammetry (DPV). p-l-Lys film was immobilized on a glassy carbon electrode (GCE) by cyclic voltammetry between 0.0 and 1.9 V in 20 mM phosphate buffer solution (pH 8.6). After the p-l-Lys/GCE electrode was incubated with D-Trp solution containing Cu(II) ions, obvious enhancement of electron transfer resistance and decrease of voltammetric current could be observed. If D-Trp was replaced by L-tryptophan (l-Trp), there was no apparent resistance and current changes. Moreover, no resistance and current changes could be found in the absence of Cu(II). It may be due to the formation of Cu complex with L-lysine and D-tryptophan. Finally, this method was successfully applied to monitoring enantiomeric composition of the D-Trp and l Trp mixtures. PMID- 26364950 TI - An integrated microfluidic system for bovine DNA purification and digital PCR detection. AB - In this paper, we described an integrated modularized microfluidic system that contained two distinct functional modules, one for nucleic acids (NA) extraction and the other for digital PCR (dPCR), allowing for detecting the bovine DNA in ovine tissue. PMID- 26364951 TI - Complete mitochondrial genome sequence of the hedgehog seahorse Hippocampus spinosissimus Weber, 1933 (Gasterosteiformes:Syngnathidae). AB - The complete mitochondrial genome sequence of the hedgehog seahorse Hippocampus spinosissimus was first determined in this article. The total length of H. spinosissimus mitogenome is 16 527 bp and consists of 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes and 1 control region. The gene order and composition of H. spinosissimus were similar to those of most other vertebrates. The overall base composition of H. spinosissimus is 32.1% A, 30.3% T, 14.9% G and 22.7% C, with a slight A + T-rich feature (62.4%). Phylogenetic analyses based on complete mitochondrial genome sequence showed that H. spinosissimus has a close genetic relationship to H. ingens and H. kuda. PMID- 26364952 TI - Pregnancy planning in type 1 diabetic women improves glycemic control and pregnancy outcomes. AB - OBJECTIVE: Pregnancy in women with type 1 diabetes is associated with increased risks. The aim of this study was to evaluate the effect of pregnancy planning on outcomes of type 1 diabetic pregnancies. METHODS: We retrospectively assessed pregnancy outcomes of type 1 diabetic women who were patients of Diabetes Clinic of North Karelia hospital between 2000 and 2012. We evaluated the medical records of 73 women experiencing 145 pregnancies and data of their infants. RESULTS: Altogether 96 (66.2%) pregnancies were planned. HbA1c levels were significantly lower before and during the whole pregnancy when pregnancy was planned than if it was not planned (all p <0.001). Planned pregnancies resulted in significantly fewer congenital anomalies (p <0.001). Pregnancy planning reduced the age adjusted risk of Cesarean sections (OR 0.25, p = 0.021). Pregnancy planning was associated with a reduced risk of adverse pregnancy outcomes (including miscarriages and congenital anomalies). This association was independent of age, HbA1c before pregnancy, smoking, hypertension, microvascular complications, and thyroid disease (OR 0.26; 95% CI 0.09, 0.76). CONCLUSIONS: Pregnancy planning is beneficial for glycemic control and pregnancy outcomes of type 1 diabetic women. The benefit of pregnancy planning was independent of other risk factors for adverse pregnancy outcomes. PMID- 26364953 TI - No medium-term advantage of electrochemical deposition of hydroxyapatite in cementless femoral stems. 5-year RSA and DXA results from a randomized controlled trial. AB - BACKGROUND AND PURPOSE: Hydroxyapatite has been used for a long time as an adjunct to enhance cementless fixation. The benefit of this is still debated, but new methods of hydroxyapatite deposition have emerged, offering possible gains. In order to investigate this further, we compared the migration pattern and periprosthetic bone remodeling in a cementless femoral stem with either electrochemically deposited hydroxyapatite-called Bonemaster (BM)-or a conventional plasma-sprayed hydroxyapatite (HA) coating. PATIENTS AND METHODS: 55 hips were randomized to either BM or HA cementless femoral stems. Patients were followed with radiostereometry (RSA), dual-energy X-ray absorptiometry (DXA), radiographic measurements, and hip questionnaires for 5 years. RESULTS: For both stems, migration occurred mainly as subsidence and retroversion during the first 3 months. The BM group had a higher retroversion rate of 0.17 degrees per month during this period, as compared to 0.06 degrees per month for the HA group (p = 0.006). Thereafter, there was almost no movement in any direction for both stem types. Bone resorption occurred mainly during the first year, and subsequently decreased to a rate close to what is seen in normal ageing. The greatest total decrease occurred in Gruen zones 1 and 7, similar in the groups at 5 years. There was a slightly higher resorption rate in Gruen zone 7 from 2 to 5 years in the BM group (1.3% per year; p = 0.04), but in a magnitude that would scarcely affect stem stability or survival. INTERPRETATION: There were no clinically relevant differences between the 2 stems regarding stability or periprosthetic bone loss at 5 years. Electrochemically deposited HA does not appear to affect fixation or bone remodeling when compared to conventional plasma spraying at 5 years. Thus, at this point, Bonemaster appears to be safe. PMID- 26364955 TI - Relationship Between Hyperuricemia and Cardiovascular Disease Risk Factors in a Chinese Population: A Cross-Sectional Study. AB - BACKGROUND: To study the relationship between hyperuricemia and cardiovascular diseases (CVDs) risk factors in a Chinese population. MATERIAL AND METHODS: Data analyzed in this study were from the Chinese Hyperuricemia and Gout Database. Indicators of serum uric acid (SUA) level, height, weight, systolic blood pressure (SBP), diastolic blood pressure (DBP), smoking status, alcohol consumption, blood glucose, cholesterol, and triglycerides were measured. T test, one-way analysis of variance, Pearson's correlation, multivariate linear regression, and multivariate logistic regression were used. RESULTS: Compared with normouricemic men, hyperuricemic men had greater height (P<0.01), weight (P<0.001), body mass index (BMI) (P<0.001), SBP (P<0.01), DBP (P<0.001), cholesterol (P<0.01), and triglyceride (P<0.001). Compared with normouricemic women, hyperuricemic women were older (P<0.01) and had greater weight (P<0.05), BMI (P<0.01), SBP (P<0.01), DBP (P<0.05), glucose (P<0.05), and triglyceride (P<0.001). In men, an increase of 1 mg/dL in SUA was associated with a 0.279 kg/m2 increase in BMI (P<0.001), a 2.438 mg/dL increase in cholesterol (P<0.05), a 10.358 mg/dL increase in triglyceride (P<0.001), and a 3.1 mg/dL decrease in glucose (P<0.01). In women, an increase of 1 mg/dL SUA was associated with a 0.168 kg/m2 increase in BMI (P<0.01) and a 3.708 mg/dL increase in triglyceride (P<0.01). After adjustment, SUA was strongly associated with obesity and hyperlipidemia in both sexes. CONCLUSIONS: Elevated serum uric acid concentration was strongly associated with obesity and hyperlipidemia in both men and women. These results indicated that, among hyperuricemia patients, we should pay more attention to the possibility of cardiovascular complications. These results might provide a novel target or a possible new treatment for cardiovascular diseases by lowering the level of serum uric acid. PMID- 26364956 TI - Prolidase-Associated Trace Elements (Mn, Zn, Co, and Ni) in the Patients with Parkinson's Disease. AB - Micronutrients and trace elements have been identified to play an important role in the development of Parkinson's disease (PD). In our previous study, we observed that prolidase activity is associated with oxidative stress and progression of PD. In present study, we aimed to study the association of prolidase-associated trace elements, such as Co, Mn, Ni, and Zn in the plasma of patients with PD by inductively coupled plasma spectrometry. Plasma levels of Co, Mn, and Ni were significantly increased, whereas plasma levels of Zn was significantly decreased (all P < 0.05) in the patients with PD than healthy controls. Plasma prolidase activity was not correlated to its associated trace elements in PD. A positive, linear, and significant correlation was observed between age and Co, and Mn, and Ni while negative and non-significant between age and status of Zn in the patients. Co, Mn, and Ni were continually elevated with increase in age as well as duration of disease in the patients with PD, whereas status of Zn was continually decreased. Thus, the study concluded that trace elements Co, Ni, and Mn status were increased and Zn status was decreased in the plasma of patients with PD. It is also concluded that elevated Co, Mn, and Ni has been associated with progression of Parkinson's disease. PMID- 26364954 TI - The immune response of stem cells in subretinal transplantation. AB - Stem cell transplantation is a potential curative treatment for degenerative diseases of the retina. Among cell injection sites, the subretinal space (SRS) is particularly advantageous as it is maintained as an immune privileged site by the retinal pigment epithelium (RPE) layer. Thus, the success of subretinal transplantation depends on maintenance of RPE integrity. Moreover, both embryonic stem cells (ESCs) and mesenchymal stem cells (MSCs) have negligible immunogenicity and in fact are immunosuppressive. Indeed, many studies have demonstrated that immunosuppressive drugs are not necessary for subretinal transplantation of stem cells if the blood-retinal barrier is not breached during surgery. The immunogenicity of induced pluripotent stem cells (iPSCs) appears more complex, and requires careful study before clinical application. Despite low rates of graft rejection in animal models, survival rates for ESCs, MSCs, and iPSCs in retina are generally poor, possibly due to resident microglia activated by cell transplantation. To improve graft survival in SRS transplantation, damage to the blood-retinal barrier must be minimized using appropriate surgical techniques. In addition, agents that inhibit microglial activation may be required. Finally, immunosuppressants may be required, at least temporarily, until the blood-retinal barrier heals. We review surgical methods and drug regimens to enhance the likelihood of graft survival after SRS transplantation. PMID- 26364958 TI - Determination of the painful level in osteoporotic vertebral fractures- Retrospective comparison between plain film, bone scan, and magnetic resonance imaging. AB - BACKGROUND: Determining the actual painful vertebral level is difficult when evaluating osteoporotic vertebral fracture, especially when there are acute and chronic fractures simultaneously. In this study, we retrospectively evaluated and compared the findings between plain film, bone scan, and magnetic resonance imaging (MRI) in the diagnosis of new fracture in osteoporotic vertebral fractures. METHODS: This is a retrospective clinical study of patients who were diagnosed with osteoporotic vertebral fractures using plain film, bone scan, and MRI within a 1-month interval between February 2008 and December 2012. The findings in plain film, the extent of increased uptake in bone scan, and signal change in MRI were compared to evaluate the actual level of pain. All patients received percutaneous vertebroplasty according to MR finding. Pain scores (visual analog scale) of the study patients were compared prior to and after the procedure. RESULTS: A total of 52 patients with a mean age of 79.1 years (range 59-92 years) were enrolled in this study, and were treated by vertebroplasty confirmed by MRI. It was observed that patient pain score (visual analog scale) improved from 7.6 to 2.8. Plain film examination revealed 79 vertebrae that were suspected to be compression fractures. Among the suspected vertebrae, 62 showed increased uptake in bone scan, and MRI showed bony edema change in 58 vertebrae. The consistency between bone scan and MRI was 96.9% in patients with single-level suspected fracture on plain film. There was moderate agreement (kappa was 0.56) in patients where multiple levels were noted. Fifteen vertebrae with vacuum cleft sign on plain film showed total concordance in both bone scan and MRI. CONCLUSION: For patients with single-level compression fracture, the painful level in osteoporotic vertebral fractures can be determined by plain film and bone scan testing. Vacuum cleft sign noted on plain film may be enough to localize the level of pain. However, MRI testing is further needed in multiple osteoporotic vertebral fracture patients. PMID- 26364957 TI - The effect of switching pharmacological intervention during extinction on nicotine-evoked conditioned responding in rats. AB - RATIONALE: Pharmacotherapies are often utilized to aid in smoking cessation, and switching medication when treating nicotine dependence has become more commonplace. Although common, little is known about the impact of the initial therapy on the effects of the subsequent therapy. OBJECTIVES: To begin to fill this gap in our understanding, this project determined how switching compounds that share stimulus elements with nicotine during extinction altered extinction responding and generalization of this extinction back to nicotine. METHODS: Rats were trained in a discriminated goal-tracking task where nicotine administration was followed by intermittent sucrose access; sucrose was withheld following saline administration. In experiment 1, nornicotine supplanted nicotine in extinction sessions 1-3 and then a switch to varenicline on extinction sessions 4 6 was examined. In experiment 2, the reverse was investigated; varenicline to start extinction and then a switch to nornicotine. Generalization of extinction back to the nicotine stimulus was then assessed by generating a cumulative dose effect curve. RESULTS: Generalization of extinction back to the training nicotine stimulus was greater if nornicotine had been received at any point in extinction compared to only receiving varenicline. Whereas, extinction with varenicline alone showed more generalization to lower doses of nicotine. CONCLUSIONS: A switch in cessation pharmacotherapy during extinction did not impede or enhance generalization back to the nicotine-training stimulus. The nornicotine stimulus appears to share more stimulus overlap with the 0.4 mg/kg nicotine stimulus and varenicline may share more overlap with lower nicotine doses. PMID- 26364959 TI - Clinical roles of breast 3T MRI, FDG PET/CT, and breast ultrasound for asymptomatic women with an abnormal screening mammogram. AB - BACKGROUND: Magnetic resonance imaging (MRI) and fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) show promise for molecular cancer imaging. We evaluated 3T MRI, FDG PET/CT, and ultrasound images for asymptomatic women with an abnormal screening mammogram. METHODS: The Institutional Review Board of Kaohsiung Veterans General Hospital (Kaohsiung, Taiwan) approved the study. Patients provided written informed consent. A total of 11,865 screening mammograms of 118,65 women were performed at our facility between January 2011 and December 2012. Fifty-three asymptomatic women (mean age, 53.3 years) whose screening mammograms had a Breast Imaging Reporting and Data System (BI-RADS) category of 4 or 5 were ultimately enrolled in this study. Breast 3T MRI, FDG PET/CT, and breast ultrasound were performed before biopsy. All imaging modalities were compared by lesion-by-lesion analyses. RESULTS: Fifty nine breast lesions (28 malignant and 31 benign lesions) from 53 women were analyzed. The sensitivity, specificity, and accuracy for 28 breast cancers were 96%, 77%, and 86%, respectively, for breast 3T MRI; 50%, 100%, and 76%, respectively, for FDG PET,CT; and 61%, 87%, and 74%, respectively, for breast ultrasound. One 0.8-cm invasive breast cancer was missed by the screening mammogram, but detected by breast 3T MRI and FDG PET/CT. The sensitivity for detecting breast cancer was significantly higher with MRI than with PET/CT or ultrasound (for all, p < 0.01). The specificity for detecting breast cancer was significantly higher for PET/CT than for breast MRI (p = 0.02). The sensitivity exhibited by 3T breast MRI and FDG PET/CT for 16 noninvasive breast cancers was 94% and 25%, respectively. CONCLUSION: On screening mammograms, breast 3T MRI showed higher sensitivity but less specificity than FDG PET/CT for detecting asymptomatic breast cancers. PMID- 26364960 TI - Malignant mesothelioma with fungating masses and multiple sites involvement. AB - Malignant mesothelioma (MM) is a rare tumor associated with asbestos exposure. It typically presents as thickening or nodularity of the pleura, although it can also originate from other sites consisting of mesothelia and have manifestations other than thickening or nodularity. Several studies have implied that these different manifestations are associated with a different tumor biology. We report the case of a 54-year-old man with multiple fungating masses diagnosed as MM on histological examination. PMID- 26364961 TI - Prothymosin-alpha preconditioning activates TLR4-TRIF signaling to induce protection of ischemic retina. AB - Prothymosin-alpha protects the brain and retina from ischemic damage. Although prothymosin-alpha contributes to toll-like receptor (TLR4)-mediated immnunopotentiation against viral infection, the beneficial effects of prothymosin-alpha-TLR4 signaling in protecting against ischemia remain to be elucidated. In this study, intravitreal administration of prothymosin-alpha 48 h before induction of retinal ischemia prevented retinal cellular damage as evaluated by histology, and retinal functional deficits as evaluated by electroretinography. Prothymosin-alpha preconditioning completely prevented the ischemia-induced loss of ganglion cells with partial survival of bipolar and photoreceptor cells, but not amacrine cells, in immunohistochemistry experiments. Prothymosin-alpha treatment in the absence of ischemia caused mild activation, proliferation, and migration of retinal microglia, whereas the ischemia-induced microglial activation was inhibited by prothymosin-alpha preconditioning. All these preventive effects of prothymosin-alpha preconditioning were abolished in TLR4 knock-out mice and by pre-treatments with anti-TLR4 antibodies or minocycline, a microglial inhibitor. Prothymosin-alpha preconditioning inhibited the retinal ischemia-induced up-regulation of TLR4-related injury genes, and increased expression of TLR4-related protective genes. Furthermore, the prothymosin-alpha preconditioning-induced prevention of retinal ischemic damage was abolished in TIR-domain-containing adapter-inducing interferon-beta knock-out mice, but not in myeloid differentiation primary response gene 88 knock-out mice. Taken together, the results of this study suggest that prothymosin-alpha preconditioning selectively drives TLR4-TIR-domain-containing adapter-inducing interferon-beta signaling and microglia in the prevention of retinal ischemic damage. We propose the following mechanism for prothymosin-alpha (ProTalpha) preconditioning-induced retinal prevention against ischemia: ProTalpha preconditioning-induced prevention of retinal ischemic damage is mediated by selective activation of the TIR-domain-containing adapter-inducing interferon beta (TRIF)- interferon regulatory factor 3 (IRF3) pathway downstream of toll like receptor 4 (TLR4) in microglia, resulting in up-regulation of TRIF-IRF3 dependent protective genes and down-regulation of myeloid differentiation primary response gene 88 (MyD88)-Nuclear factor (NF)kappaB-dependent injury genes. Detailed investigations would be helpful to test the efficacy of ProTalpha as a therapeutic agent for the prevention of ischemic disorders. PMID- 26364962 TI - [Cardiovascular disease and systemic inflammatory diseases]. AB - More than a century of research has shown that atherosclerosis is an inflammatory process more than an infiltrative or thrombogenic process. It has been demonstrated epidemiologically and by imaging techniques, that systemic inflammatory diseases (in particular, but not exclusively, rheumatoid arthritis and systemic lupus erythematosus) increase the atherosclerotic process, and has a demonstrated pathophysiological basis. Furthermore, treatments to control inflammatory diseases can modify the course of the atherosclerotic process. Although there are no specific scales for assessing cardiovascular risk in patients with these diseases, cardiovascular risk is high. A number of specific risk scales are being developed, that take into account specific factors such as the degree of inflammatory activity. PMID- 26364963 TI - Long-term outcomes of endoscopic gallbladder stenting in high-risk surgical patients with calculous cholecystitis (with videos). AB - BACKGROUND AND AIMS: Recently, endoscopic gallbladder stenting (EGBS) has been performed to prevent recurrences in high-risk surgical patients with cholecystitis. However, evidence regarding the long-term outcomes of EGBS is sparse. We investigated the cholecystitis recurrence rate in high-risk surgical patients with acute calculous cholecystitis and compared the cholecystitis recurrence rates in patients in whom EGBS was performed with those in patients who were observed after percutaneous drainage. METHODS: We studied 64 consecutive high-risk surgical patients with acute calculous cholecystitis who required gallbladder decompression between 2007 and 2014. We divided the patient cohort into patients who underwent observation after percutaneous drainage between 2007 and 2011 (OAPD group) and those who underwent EGBS between 2012 and 2014 (EGBS group), and we compared the groups. RESULTS: The technical success rate of EGBS was 82.9% based on the intention-to-treat analysis. The cholecystitis recurrence rates were 17.2% in the OAPD group and 0% in the EGBS group, a difference that was significant (P = .043). There was also a significant difference between the groups with respect to the time to recurrent cholecystitis, which was determined by using Kaplan-Meier analysis (P = .015). The overall biliary event rates were 24.1% in the OAPD group and 9.1% in the EGBS group, and no significant difference was noted (P = .207). CONCLUSION: EGBS reduced the recurrence of cholecystitis in high-risk surgical patients with calculous cholecystitis. However, stent-related adverse events may occur, and modifications are necessary to reduce these. PMID- 26364964 TI - Facilitating retroflexed endoscopic full-thickness resection through loop mediated or rope-mediated countertraction (with videos). AB - BACKGROUND AND AIMS: Endoscopic full-thickness resection (EFTR) is difficult to perform in a retroflexed fashion in the gastric fundus and lesser curvature. Here we describe two simple methods to provide countertraction and thereby facilitate dissection. METHODS: In this retrospective cohort study, 62 patients diagnosed as having gastric submucosal tumors in the fundus or in the lesser curvature received EFTR with or without countertraction methods. For the clip-with-thread method, a clip tied with surgical suture was anchored on the distal edge of the tumor to provide countertraction; for the loop-assisted method, a snare placed on the transparent cap beforehand was adopted to grasp the tumor to provide countertraction. RESULTS: Mean operative time was significantly reduced in the thread-with-clip group and loop-assisted group (45 minutes, 40 minutes, respectively) compared with the time needed in the traditional EFTR group (85 minutes). Intraoperative pneumoperitoneum occurred regularly among the 3 groups because of iatrogenic perforation, but fewer patients in the thread-with-clip group and loop-assisted group (23%, 18%, respectively) needed abdominal puncture to relieve free air and stabilize life signs compared with patients in the traditional EFTR group (63%). A reduced occurrence of high fever after surgery may contribute as another advantage from accelerated dissection. Both techniques did not jeopardize oncologic safety during short-term follow-up. CONCLUSIONS: Both the thread-with-clip method and loop-assisted method provide effective countertraction and offer faster and safer gastric EFTR in difficult anatomic locations. PMID- 26364965 TI - Endoscopic management of colonic perforations: clips versus suturing closure (with videos). AB - BACKGROUND AND AIMS: Perforation during colonoscopy remains the most worrisome adverse event and usually requires urgent surgical rescue. The aim of this study was to evaluate the feasibility and effectiveness of endoscopic closure of full thickness colonic perforations. METHODS: We performed a retrospective analysis of all consecutive patients with endoscopically closed colonic perforations over the past 6 years (2009-2014). Colonic perforations were closed by using endoscopic clips or an endoscopic suturing device. Most patients were admitted for treatment with intravenous antibiotics and kept on bowel rest. If their clinical condition deteriorated, urgent surgery was performed. If patients remained stable, oral feeding was resumed, and patients were discharged with subsequent clinical and endoscopic follow-up. RESULTS: Twenty-one patients had iatrogenic colonic perforations closed with an endoscopic suturing device or endoscopic clips during the study period. Primary closure of a colonic perforation was performed with endoscopic clips in 5 patients and sutured with an endoscopic suturing device in 16 patients. All 5 patients after clip closure had worsening of abdominal pain and required laparoscopy (4 patients) or rescue colonoscopy with endoscopic suturing closure (1 patient). Two patients had abdominal pain after endoscopic suturing closure, but diagnostic laparoscopy confirmed complete and adequate endoscopic closure of the perforations. The other 15 patients did not require any rescue surgery or laparoscopy after endoscopic suturing. The main limitation of our study is its retrospective, single-center design and relatively small number of patients. CONCLUSION: Endoscopic suturing closure of colonic perforations is technically feasible, eliminates the need for rescue surgery, and appears more effective than closure with hemostatic endoscopic clips. PMID- 26364966 TI - The influence of clips on scars after EMR: clip artifact. AB - BACKGROUND AND AIMS: Laterally spreading lesions >=20 mm are conventionally removed by EMR. Endoscopic clips are increasingly used to mitigate the risk of delayed bleeding. Clips may alter the endoscopic appearance of the scar after EMR, interfering with the assessment of adenoma recurrence. We aimed to evaluate this. METHODS: Prospective, single-center data from the Australian Colonic Endoscopic resection study (January 2011-May 2015) were analyzed. Patients undergoing EMR of laterally spreading lesions with endoscopic clips used at the EMR defect were eligible. Data included patient and lesion characteristics and procedural, clinical, and histologic outcomes. RESULTS: Clips were used in 111 of 885 lesions (12.5%). A total of 62 of 111 clipped lesions had standardized, high definition, white light, and narrow-band images of the scars after EMR at first surveillance colonoscopy, and the patients were enrolled. Analysis of the images showed 4 situations: a bland scar (N = 27), residual adenoma (N = 6), mucosal elevation with normal pit pattern (N = 14), or granulation tissue related to the presence of residual clips (N = 15). The latter 2 entities were termed post-EMR scar clip artifact (ESCA). Overall, 29 of 62 previously clipped EMR sites (46.8%) had ESCA at a median follow-up of 5.2 months. Twenty scars had residual clips, and 15 of 20 (75.0%) showed ESCA (P = .002). Lesions clipped for prophylaxis of bleeding were more likely to show ESCA than those clipped for deep mural injury or intraprocedural bleeding (65.5% vs 41.7%; P = .006). ESCA was associated with female sex (P = .010) and greater age (P = .011). CONCLUSIONS: ESCA is characterized by a nodular elevation of the mucosa with a normal pit pattern and can occur with or without residual clips. Prophylactic clip closure and the presence of residual clips are associated with ESCA. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT01368289.). PMID- 26364967 TI - A roadmap to the implementation of chromoendoscopy in inflammatory bowel disease colonoscopy surveillance practice. PMID- 26364968 TI - A randomized, controlled trial to compare the efficacy and safety profile of a dexmedetomidine-ketamine combination with a propofol-fentanyl combination for ERCP. AB - BACKGROUND AND AIMS: Moderate to deep levels of sedation and analgesia are required for ERCP. Propofol-based sedation is simple, easy to use, and effective, but is not without cardiovascular and respiratory adverse effects. The combination of dexmedetomidine and ketamine (DK) has shown promising results for sedation in other similar scenarios. The aim of this study was to compare the efficacy and safety of a standard propofol-fentanyl (PF) regimen with a DK combination. METHODS: After approval of the hospital ethics committee, 83 patients (18-75 years of age) were randomized and divided into 2 groups. Forty two patients received a PF combination (group PF) and 41 patients received DK combination (group DK) for total intravenous anesthesia for ERCP as initial boluses followed by an infusion of PF and DK, respectively. The sedation-related adverse effects and recovery time were noted. RESULTS: The mean values of the hemodynamic and respiratory parameters were in clinically acceptable ranges, but there were more episodes of hypotension (19%), bradycardia (4.7%), and decrease in oxygen saturation (Spo(2) <80% in 11.9% and Spo(2) <90% for >10 s in 42.8%) in group PF. The procedure could be completed in all of the patients but was interrupted in 6 patients in group PF because of desaturation (5) or sudden patient movement (1). The recovery time was longer in group DK than in group PF. CONCLUSION: There were significantly fewer sedation-related adverse effects, but the recovery time was longer with DK. PMID- 26364970 TI - von Willebrand activation factor as a marker of mortality, cardiovascular events, and bleeding complications in patients treated with oral anticoagulants. AB - BACKGROUND: Serious bleeding is a frequent and feared treatment complication in patients treated with oral anticoagulants (OACs). Levels of von Willebrand factor (VWF) antigen have been linked to the risk of bleeding complications, mortality, and cardiovascular events. OBJECTIVES: In this longitudinal cohort study of evaluating patients treated with OACs, we aimed to evaluate the relationship between VWF displaying a glycoprotein Ib binding conformation (VWF activation factor) and the risk of cardiovascular events, bleeding complications, or all cause mortality. MATERIALS AND METHODS: Blood samples were collected at baseline in 356 patients on OACs. Patients were followed for an average of 48 months and bleeding complications leading to admission to hospital or death, cardiovascular events (myocardial infarction, ischemic stroke, and peripheral arterial emboli), and all-cause mortality were recorded and classified. RESULTS: During the study period, 47 bleeding complications, 84 cardiovascular events, and 97 deaths occurred. In multivariate Cox regression analyses, VWF activation factor was significantly associated with all-cause mortality (HR 1.62; 95% CI: 1.25-2.08) and cardiovascular events (HR 1.28; 95% CI: 1.01-1.63). There was no association observed between VWF activation factor and bleeding complications. CONCLUSIONS: Patients with high levels of VWF activation factor had an increased risk of cardiovascular events and all-cause mortality during OAC treatment. The selectivity for thrombotic complications adds to the potential value of VWF activation factor as a biomarker or pharmacological target. PMID- 26364969 TI - Electro-magnetic field promotes osteogenic differentiation of BM-hMSCs through a selective action on Ca(2+)-related mechanisms. AB - Exposure to Pulsed Electromagnetic Field (PEMF) has been shown to affect proliferation and differentiation of human mesenchymal stem cells derived from bone marrow stroma (BM-hMSC). These cells offer considerable promise in the field of regenerative medicine, but their clinical application is hampered by major limitations such as poor availability and the time required to differentiate up to a stage suitable for implantation. For this reason, several research efforts are focusing on identifying strategies to speed up the differentiation process. In this work we investigated the in vitro effect of PEMF on Ca(2+)-related mechanisms promoting the osteogenic differentiation of BM-hMSC. Cells were daily exposed to PEMF while subjected to osteogenic differentiation and various Ca(2+) related mechanisms were monitored using multiple approaches for identifying functional and structural modifications related to this process. The results indicate that PEMF exposure promotes chemically induced osteogenesis by mechanisms that mainly interfere with some of the calcium-related osteogenic pathways, such as permeation and regulation of cytosolic concentration, leaving others, such as extracellular deposition, unaffected. The PEMF effect is primarily associated to early enhancement of intracellular calcium concentration, which is proposed here as a reliable hallmark of the osteogenic developmental stage. PMID- 26364971 TI - Phylogeny of haemosporidian blood parasites revealed by a multi-gene approach. AB - The apicomplexan order Haemosporida is a clade of unicellular blood parasites that infect a variety of reptilian, avian and mammalian hosts. Among them are the agents of human malaria, parasites of the genus Plasmodium, which pose a major threat to human health. Illuminating the evolutionary history of Haemosporida may help us in understanding their enormous biological diversity, as well as tracing the multiple host switches and associated acquisitions of novel life-history traits. However, the deep-level phylogenetic relationships among major haemosporidian clades have remained enigmatic because the datasets employed in phylogenetic analyses were severely limited in either gene coverage or taxon sampling. Using a PCR-based approach that employs a novel set of primers, we sequenced fragments of 21 nuclear genes from seven haemosporidian parasites of the genera Leucocytozoon, Haemoproteus, Parahaemoproteus, Polychromophilus and Plasmodium. After addition of genomic data from 25 apicomplexan species, the unreduced alignment comprised 20,580 bp from 32 species. Phylogenetic analyses were performed based on nucleotide, codon and amino acid data employing Bayesian inference, maximum likelihood and maximum parsimony. All analyses resulted in highly congruent topologies. We found consistent support for a basal position of Leucocytozoon within Haemosporida. In contrast to all previous studies, we recovered a sister group relationship between the genera Polychromophilus and Plasmodium. Within Plasmodium, the sauropsid and mammal-infecting lineages were recovered as sister clades. Support for these relationships was high in nearly all trees, revealing a novel phylogeny of Haemosporida, which is robust to the choice of the outgroup and the method of tree inference. PMID- 26364972 TI - Phylogenetic relationships and evolutionary history of the Mesoamerican endemic freshwater fish family Profundulidae (Cyprinodontiformes: Actinopterygii). AB - Freshwater fishes of Profundulidae, which until now was composed of two subgenera, represent one of the few extant fish families endemic to Mesoamerica. In this study we investigated the phylogenetic relationships and evolutionary history of the eight recognized extant species (from 37 populations) of Profundulidae using three mitochondrial and one nuclear gene markers (~2.9 Kbp). We applied a Bayesian species delimitation method as a first approach to resolving speciation patterns within Profundulidae considering two different scenarios, eight-species and twelve-species models, obtained in a previous phylogenetic analysis. Based on our results, each of the two subgenera was resolved as monophyletic, with a remarkable molecular divergence of 24.5% for mtDNA and 7.8% for nDNA uncorrected p distances, and thus we propose that they correspond to separate genera. Moreover, we propose a conservative taxonomic hypothesis with five species within Profundulus and three within Tlaloc, although both eight-species and twelve-species models were highly supported by the bayesian species delimitation analysis, providing additional evidence of higher taxonomic diversity than currently recognized in this family. According to our divergence time estimates, the family originated during the Upper Oligocene 26 Mya, and Profundulus and Tlaloc diverged in the Upper Oligocene or Lower Miocene about 20 Mya. PMID- 26364973 TI - Protective effect of gallic acid and Syzygium cumini extract against oxidative stress-induced cellular injury in human lymphocytes. AB - CONTEXT: Syzygium cumini (Myrtaceae) presents antioxidant, anti-inflammatory, hypoglycemic and antibacterial effects; however, the cellular and molecular mechanisms of action in the immune system are not yet completely elucidated. OBJECTIVE: This study evaluates the in vitro effect of gallic acid and aqueous S. cumini leaf extract (ASc) on adenosine deaminase (ADA) and dipeptidyl peptidase IV (DPP-IV) activities, cell viability and oxidative stress parameters in lymphocytes exposed to 2, 2'-azobis-2-amidinopropane dihydrochloride (AAPH). MATERIALS AND METHODS: Lymphocytes were incubated with ASc (100 and 500 ug/ml) and gallic acid (50 and 200 uM) at 37 degrees C for 30 min followed by incubation with AAPH (1 mM) at 37 degrees C for 2 h. After the incubation time, the lymphocytes were used for determinations of ADA, DPP-IV and lactate dehydrogenase (LDH) activities, lipid peroxidation, protein thiol (P-SH) group levels and cellular viability by colorimetric methods. RESULTS: (i) HPLC fingerprinting of ASc revealed the presence of catechin, epicatechin, rutin, quercitrin, isoquercitrin, quercetin, kaempferol and chlorogenic, caffeic, gallic and ellagic acids; (ii) for the first time, ASc reduced the AAPH-induced increase in ADA activity, but no effect was observed on DPP-IV activity; (iii) ASc increased P-SH groups and cellular viability and decreased LDH activity, but was not able to reduce the AAPH-induced lipid peroxidation; (iv) gallic acid showed less protective effects than ASc. DISCUSSION AND CONCLUSION: ASc affects the purinergic system and may modulate adenosine levels, indicating that the extract of this plant exhibits immunomodulatory properties. ASc also may potentially prevent the cellular injury induced by oxidative stress, highlighting its cytoprotective effects. PMID- 26364974 TI - Global transcriptional profiling of longissimus thoracis muscle tissue in fetal and juvenile domestic goat using RNA sequencing. AB - Domestic goats are important meat production animals; however, data from transcriptional profiling of skeletal muscle tissue in goat have thus far been scarce. We used comparative transcriptional profiling based on RNA sequencing of longissimus thoracis muscle tissue obtained from fetal goat muscle tissue (27 512 850 clean cDNA reads) and 6-month-old goat muscle tissue (27 582 908 reads) to identify genes that are differentially expressed, novel transcript units and alternative splicing events. Gene annotation revealed that 15 960 and 14 981 genes were expressed in the fetal and juvenile libraries respectively. We detected 6432 differentially expressed genes and, when considering GO terms, found 34, 27 and 55 terms to be significantly enriched in molecular function, cellular component and biological process categories respectively. Pathway analysis revealed that larger numbers of differentially expressed genes were enriched in fetal myogenesis or cell proliferation and differentiation-related pathways (such as Wnt), genes involved in the cell cycle and the Notch signaling pathway, and most of the differentially expressed genes involved in these pathways were downregulated in the juvenile goat library. These genes may be involved in various regulation mechanisms during muscle tissue differentiation between the two development stages examined herein. The identified novel transcript units, including both non-coding and coding RNA, as well as alternative splicing events increase the level of complexity of regulation mechanisms during muscle tissue formation and differentiation. Our study provides a comparative transcriptome analysis on goat muscle tissue, which will provide a valuable genomic resource for future studies investigating the molecular basis of skeletal muscle development. PMID- 26364975 TI - Multidrug therapy of Mycobacterium avium subsp. avium infection in experimentally inoculated budgerigars (Melopsittacus undulatus). AB - The aim of the study was to determine whether the four-month experimental therapy of mycobacteriosis in budgerigars may cause a complete recovery. A group of nine budgerigars was infected with a Mycobacterium avium subsp. avium isolate with proven pathogenicity for budgerigars. Five weeks post-inoculation, multidrug therapy was started. Another group comprising six birds received the same treatment but no infection, and the third group also comprising six birds was kept without infection or treatment as a control. The adopted antibiotic regimen included clarithromycin 61 mg/kg b.w., moxifloxacin 25 mg/kg b.w. and ethambutol 60 mg/kg b.w. administered by crop gavage every 12 h for 18 weeks. Despite a significant improvement in the condition of the infected, treated birds, the four month therapy was not sufficient for the complete recovery of all. PMID- 26364977 TI - Hydrophilic and blue fluorescent N-doped carbon dots from tartaric acid and various alkylol amines under microwave irradiation. AB - The desired control of particle size, doping element composition, and surface structure of carbon dots (CDs) are vital for understanding the fluorescence mechanism and exploring their potential applications. Herein, nitrogen-doped CDs (N-doped CDs) have been synthesized with tartaric acid and various alkylol amines (monoethanolamine, biethanolamine and triethanolamine) under microwave irradiation. A systematic investigation was performed to characterize the N-doped CDs. It is found that with increasing nitrogen proportion, the fluorescent quantum yield and lifetime of N-doped CDs increases, whereas cell toxicity decreases. In other words, N-doped CDs synthesized by tartaric acid and monoethanolamine have the highest nitrogen content, the highest fluorescent quantum yield, the longest lifetime and the lowest cell toxicity. A corresponding mechanism has been proposed. Moreover, as-synthesized N-doped CDs have been applied for selectively detecting the Fe(3+) ion and writing letters as a fluorescent ink. PMID- 26364976 TI - Proteomic Profiling of Cranial (Superior) Cervical Ganglia Reveals Beta-Amyloid and Ubiquitin Proteasome System Perturbations in an Equine Multiple System Neuropathy. AB - Equine grass sickness (EGS) is an acute, predominantly fatal, multiple system neuropathy of grazing horses with reported incidence rates of ~2%. An apparently identical disease occurs in multiple species, including but not limited to cats, dogs, and rabbits. Although the precise etiology remains unclear, ultrastructural findings have suggested that the primary lesion lies in the glycoprotein biosynthetic pathway of specific neuronal populations. The goal of this study was therefore to identify the molecular processes underpinning neurodegeneration in EGS. Here, we use a bottom-up approach beginning with the application of modern proteomic tools to the analysis of cranial (superior) cervical ganglion (CCG, a consistently affected tissue) from EGS-affected patients and appropriate control cases postmortem. In what appears to be the proteomic application of modern proteomic tools to equine neuronal tissues and/or to an inherent neurodegenerative disease of large animals (not a model of human disease), we identified 2,311 proteins in CCG extracts, with 320 proteins increased and 186 decreased by greater than 20% relative to controls. Further examination of selected proteomic candidates by quantitative fluorescent Western blotting (QFWB) and subcellular expression profiling by immunohistochemistry highlighted a previously unreported dysregulation in proteins commonly associated with protein misfolding/aggregation responses seen in a myriad of human neurodegenerative conditions, including but not limited to amyloid precursor protein (APP), microtubule associated protein (Tau), and multiple components of the ubiquitin proteasome system (UPS). Differentially expressed proteins eligible for in silico pathway analysis clustered predominantly into the following biofunctions: (1) diseases and disorders, including; neurological disease and skeletal and muscular disorders and (2) molecular and cellular functions, including cellular assembly and organization, cell-to-cell signaling and interaction (including epinephrine, dopamine, and adrenergic signaling and receptor function), and small molecule biochemistry. Interestingly, while the biofunctions identified in this study may represent pathways underpinning EGS-induced neurodegeneration, this is also the first demonstration of potential molecular conservation (including previously unreported dysregulation of the UPS and APP) spanning the degenerative cascades from an apparently unrelated condition of large animals, to small animal models with altered neuronal vulnerability, and human neurological conditions. Importantly, this study highlights the feasibility and benefits of applying modern proteomic techniques to veterinary investigations of neurodegenerative processes in diseases of large animals. PMID- 26364978 TI - Association between maternal Group B Streptococcus surface-protein antibody concentrations and invasive disease in their infants. AB - OBJECTIVES: Group B Streptococcus (GBS) surface-proteins have been shown to be immunogenic and potential vaccine candidates. We aim to determine the association between maternal IgG antibodies to select GBS surface-proteins and invasive GBS disease in their infants. METHODS: Using a matched case-control study, maternal antibody levels for GBS-immunogenic bacterial adhesin, fibrinogen-binding protein A and pilus-island (PI) PI-1, PI-2a, PI-2b were compared between infants with invasive GBS disease and well-baby controls. RESULTS: The absolute risk of disease did not differ between cases and colonized controls with increasing antibody concentrations for these surface-proteins. There was, however, a relative risk reduction in invasive disease associated with fibrinogen-binding protein A, with an adjusted odds ratio of 0.04 (95% CI: 0.01-0.69) at antibody levels >=10,000 AU/ml. CONCLUSION: We have not demonstrated an association between naturally occurring fibrinogen-binding protein A, GBS-immunogenic bacterial adhesin, and PI surface-protein antibodies and the risk of invasive disease in young infants. These surface-proteins may not be suitable GBS vaccine candidates. PMID- 26364980 TI - Physical Health Problems and Barriers to Optimal Health Care Among Children in Foster Care. AB - Children and adolescents in foster care placement represent a unique population with special health care needs, often resulting from pre-placement early adversity and neglected, unaddressed health care needs. High rates of all health problems, including acute and/or chronic physical, mental, and developmental issues prevail. Disparities in health status and access to health care are observed. This article summarizes the physical health problems of children in foster care, who are predisposed to poor health outcomes when complex care needs are unaddressed. Despite recognition of the significant burden of health care need among this unique population, barriers to effective and optimal health care delivery remain. Legislative solutions to overcome obstacles to health care delivery for children in foster care are discussed. PMID- 26364979 TI - Living without DAT: Loss and compensation of the dopamine transporter gene in sauropsids (birds and reptiles). AB - The dopamine transporter (DAT) is a major regulator of synaptic dopamine (DA) availability. It plays key roles in motor control and motor learning, memory formation, and reward-seeking behavior, is a major target of cocaine and methamphetamines, and has been assumed to be conserved among vertebrates. We have found, however, that birds, crocodiles, and lizards lack the DAT gene. We also found that the unprecedented loss of this important gene is compensated for by the expression of the noradrenaline transporter (NAT) gene, and not the serotonin transporter genes, in dopaminergic cells, which explains the peculiar pharmacology of the DA reuptake activity previously noted in bird striatum. This unexpected pattern contrasts with that of ancestral vertebrates (e.g. fish) and mammals, where the NAT gene is selectively expressed in noradrenergic cells. DA circuits in birds/reptiles and mammals thus operate with an analogous reuptake mechanism exerted by different genes, bringing new insights into gene expression regulation in dopaminergic cells and the evolution of a key molecular player in reward and addiction pathways. PMID- 26364981 TI - Catalytic Asymmetric Iodocyclization of N-Tosyl Alkenamides using Aminoiminophenoxy Copper Carboxylate: A Concise Synthesis of Chiral 8-Oxa-6 Azabicyclo[3.2.1]octanes. AB - A newly developed aminoiminophenoxy copper carboxylate (L7-Cu-OAc)-catalyzed asymmetric iodocyclization of N-Tosyl alkenamides gave O-cyclized products in good yields with high enantioselectivity. From the O-cyclized products, a skeletal transformation was succeeded in the synthesis of biologically important chiral 8-oxa-6-azabicyclo[3.2.1]octanes. DFT calculations suggested that the acetoxy anion of the [L7-Cu-OAc] acts as a base to generate the anion of N-Tosyl alkenamide substrates. The exchanged acetic acid reconstructs a new hydrogen bonding network between the catalyst and the substrates to accomplish the highly efficient asymmetric O-iodocyclization of N-Tosyl alkenamides. PMID- 26364982 TI - Is it possible to enhance the organism's resistance to toxic effects of metallic nanoparticles? PMID- 26364983 TI - Macrodactyly as a Presenting Sign of Maffucci Syndrome. PMID- 26364984 TI - Pharmacokinetics of Oral Methadone in the Treatment of Neonatal Abstinence Syndrome: A Pilot Study. AB - OBJECTIVE: To characterize the population pharmacokinetics of oral methadone in neonates requiring pharmacologic treatment of neonatal abstinence syndrome and to develop a pharmacokinetic (PK) model toward an evidence-based treatment protocol. STUDY DESIGN: Based on a methadone dosing protocol, serum concentrations of methadone and its metabolites were assessed by high performance liquid chromatography-tandem mass spectrometry from dried blood spots. Population PK analysis was performed to determine the volume of distribution and clearance of oral methadone. Methadone plasma concentration-time profiles were simulated from the deduced PK model to optimize the dosing regimen. RESULTS: There was substantial interindividual variability in methadone concentrations. Blood concentrations of methadone were best described by a 1-compartment model with first-order absorption. The population mean estimates (coefficient of variation percentage) for oral clearance and volume of distribution were 8.94 (103%) L/h/70 kg and 177 (133%) L/70 kg, respectively. Optimized dosing strategies were developed based on the simulated PK profiles. We suggest a starting dose of 0.1 mg/kg per dose every 6 hours for most patients requiring pharmacologic treatment of neonatal abstinence syndrome followed by an expedited weaning phase. CONCLUSIONS: The proposed dosing regimen may reduce the cumulative dose of opioid and shorten the length of hospitalization. Future studies should aim to validate the simulated dosing schemes with clinical data and expand our understanding of the between-patient PK variability. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01754324. PMID- 26364985 TI - Children with Chronic Hepatitis B in the United States and Canada. AB - OBJECTIVES: To test the hypothesis that children with chronic hepatitis B living in the US and Canada would have international origins and characteristic hepatitis B virus (HBV) genotypes and laboratory profiles. STUDY DESIGN: Clinical characteristics of children enrolled in the Hepatitis B Research Network were collected from 7 US and Canadian centers. RESULTS: Children (n = 343) with an age range of 1.0-17.8 years were enrolled; 78% of the children were Asian, 55% were adopted, and 97% had international origins with either the child or a parent born in 1 of 31 countries. The majority had HBV genotype B (43%) or C (32%), and the remainder had genotype A (5%), D (16%), E (4%), or multiple (<1%). Children with genotype B or C were more likely to be Asian (98% and 96%), more consistently hepatitis B envelope antigen positive (95% and 82%), had higher median HBV DNA levels (8.2 and 8.3 log10 IU/mL), and less frequently had elevated alanine aminotransferase values (43% and 57%) compared with children with other genotypes. The percentage of hepatitis B envelope antigen positivity and of those with HBV DNA >=6 log10 IU/mL declined with age. CONCLUSIONS: The majority of children in the Hepatitis B Research Network have HBV genotypes that reflect their international origins. Clinical and laboratory data differ substantially by patient age and HBV genotype. Use of these data can help drive the development of optimal strategies to manage and treat children with chronic hepatitis B. PMID- 26364987 TI - The influence of bacterial interaction on the virulence of Cryptococcus neoformans. AB - Microbes exist in complex communities in the environment. The interaction between fungi, such as the opportunistic pathogen Cryptococcus neoformans, and antagonistic environmental bacteria, such as Acinetobacter spp., may influence fungal evolution through the production of fungal defence mechanisms that inadvertently enhance fungal pathogenicity. Such changes include alteration of biofilm formation and increased capsule production. The molecular mechanisms responsible for such changes, both from a bacterial and fungal point of view, are of great interest to understanding the evolution of pathogenicity. Additionally, further elucidation of the stability of the induced changes in C. neoformans, and the impacts of these change on the disease-causing potential of this fungus, is of great interest. PMID- 26364986 TI - Experimental evaluation of the zoonotic infection potency of simian retrovirus type 4 using humanized mouse model. AB - During 2001-2002 and 2008-2011, two epidemic outbreaks of infectious hemorrhagic disease have been found in Japanese macaques (Macaca fuscata) in Kyoto University Primate Research Institute, Japan. Following investigations revealed that the causative agent was simian retrovirus type 4 (SRV-4). SRV-4 was isolated by using human cell lines, which indicates that human cells are potently susceptible to SRV-4 infection. These raise a possibility of zoonotic infection of pathogenic SRV-4 from Japanese macaques into humans. To explore the possibility of zoonotic infection of SRV-4 to humans, here we use a human hematopoietic stem cell transplanted humanized mouse model. Eight out of the twelve SRV-4-inoculated humanized mice were infected with SRV-4. Importantly, 3 out of the 8 infected mice exhibited anemia and hemophagocytosis, and an infected mouse died. To address the possibility that SRV-4 adapts humanized mouse and acquires higher pathogenicity, the virus was isolated from an infected mice exhibited severe anemia was further inoculated into another 6 humanized mice. However, no infected mice exhibited any illness. Taken together, our findings demonstrate that the zoonotic SRV-4 infection from Japanese macaques to humans is technically possible under experimental condition. However, such zoonotic infection may not occur in the real society. PMID- 26364988 TI - 'Biologizing' Psychopathy: Ethical, Legal, and Research Implications at the Interface of Epigenetics and Chronic Antisocial Conduct. AB - Epigenetics, a field that links genetics and environmental influences on the expression of phenotypic traits, offers to increase our understanding of the development and trajectory of disease and psychological disorders beyond that thought of traditional genetic research and behavioural measures. By extension, this new perspective has implications for risk and risk management of antisocial behaviour where there is a biological component, such as psychopathy. Psychopathy is a personality disorder associated with repeat displays of antisocial behaviour, and is associated with the disproportionate imposition of harm on communities. Despite advances in our knowledge of psychopathic individuals, the construct remains complex and is hampered by a lack of integration across a range of fundamental domains. The clinical and forensic research on psychopathy is brought into conversation with the emerging field of epigenetics to highlight critical issues of (1) clinical definition and diagnosis, (2) assessment, (3) aetiology of psychopathic phenotypes, and (4) treatment and rehabilitation approaches. Broader ethical and legal questions of the role of epigenetic mechanisms in the management of psychopathy beyond the criminal justice arena are also outlined. PMID- 26364989 TI - Ionogel fibres of bis(trifluoromethanesulfonyl)imide anion-based ionic liquids for the headspace solid-phase microextraction of chlorinated organic pollutants. AB - Ionogels, a family of hybrid materials in which ionic liquids (ILs) are confined in a sol-gel network, are receiving much attention in a variety of scientific and technological fields. In this work, ionogels derived from three different ILs based on the anion bis(trifluoromethanesulfonyl)imide (TFSI), namely 1-butyl-3 methylpyridinium bis(trifluoromethanesulfonyl)imide ([C4C1Py][TFSI]), 1-butyl-1 methylpyrrolidinium bis(trifluoromethanesulfonyl)imide ([C4C1Pyrr][TFSI]), and 1 butyl-1-methylpiperidinium bis(trifluoromethanesulfonyl)imide ([C4C1Pip][TFSI]) were obtained on the outer surface of optical fibres by sol-gel technology. The obtained hybrid materials were characterized by scanning electron microscopy (SEM) and energy dispersive X-ray spectrometry (EDX), and subsequently evaluated as sorbent coatings for the headspace solid-phase microextraction (HS-SPME) of volatile chlorinated organic compounds in combination with gas chromatography with barrier ionization discharge detection (GC-BID). The ionogel based on [C4C1Pyrr][TFSI] exhibited the highest extractability for target analytes. The experimental parameters that affect the extraction process were optimized by means of a central composite design. Under optimal conditions, the proposed method yielded excellent enrichment factors (EFs) in the range 3889-20 919 and limits of detection (LODs) between 11 and 151 ng L(-1) for the target compounds. The inter-day repeatability, intra-day reproducibility and fibre-to-fibre reproducibility, were less than 8.5, 9.6 and 16.9%, respectively. Finally, the developed method was applied to the analysis of water samples, showing recovery values in the range 95-106%. PMID- 26364990 TI - MOF Crystal Chemistry Paving the Way to Gas Storage Needs: Aluminum-Based soc-MOF for CH4, O2, and CO2 Storage. AB - The molecular building block approach was employed effectively to construct a series of novel isoreticular, highly porous and stable, aluminum-based metal organic frameworks with soc topology. From this platform, three compounds were experimentally isolated and fully characterized: namely, the parent Al-soc-MOF-1 and its naphthalene and anthracene analogues. Al-soc-MOF-1 exhibits outstanding gravimetric methane uptake (total and working capacity). It is shown experimentally, for the first time, that the Al-soc-MOF platform can address the challenging Department of Energy dual target of 0.5 g/g (gravimetric) and 264 cm(3) (STP)/cm(3) (volumetric) methane storage. Furthermore, Al-soc-MOF exhibited the highest total gravimetric and volumetric uptake for carbon dioxide and the utmost total and deliverable uptake for oxygen at relatively high pressures among all microporous MOFs. In order to correlate the MOF pore structure and functionality to the gas storage properties, to better understand the structure property relationship, we performed a molecular simulation study and evaluated the methane storage performance of the Al-soc-MOF platform using diverse organic linkers. It was found that shortening the parent Al-soc-MOF-1 linker resulted in a noticeable enhancement in the working volumetric capacity at specific temperatures and pressures with amply conserved gravimetric uptake/working capacity. In contrast, further expansion of the organic linker (branches and/or core) led to isostructural Al-soc-MOFs with enhanced gravimetric uptake but noticeably lower volumetric capacity. The collective experimental and simulation studies indicated that the parent Al-soc-MOF-1 exhibits the best compromise between the volumetric and gravimetric total and working uptakes under a wide range of pressure and temperature conditions. PMID- 26364991 TI - The influence of sense of coherence and mindfulness on PTSD symptoms and posttraumatic cognitions in a sample of elderly Austrian survivors of World War II. AB - BACKGROUND: Sense of Coherence (SOC) and mindfulness are known protective factors against psychopathology, also in older age. We set out to investigate the influence of SOC and mindfulness on posttraumatic symptoms and cognitions in the context of lifetime trauma in elderly persons with a history of childhood war experiences. METHODS: Elderly Austrians (N = 97) filled in questionnaires on traumatic lifetime experiences and posttraumatic symptoms (ETI), posttraumatic cognitions (PTCI), SOC (SOC-13) and mindfulness (FFMQ). We expected the influence of SOC scores on posttraumatic symptoms and cognitions to be on one hand influenced by mindfulness. On the other hand, we expected that both aspects would uniquely explain fewer posttraumatic symptoms and cognitions. RESULTS: Participants reported various lifetime traumas (M = 2.42), including experiences during World War II (WWII) as children and adolescents. Mindfulness partially mediated the association of SOC scores with posttraumatic cognitions, but not with posttraumatic symptoms. However, in a two-stage mediation model, mindfulness significantly predicted posttraumatic symptoms via its effects on posttraumatic cognitions. CONCLUSION: Although SOC was the strongest predictor of posttraumatic symptoms, mindfulness influenced the severity of posttraumatic symptoms via its effects on posttraumatic cognitions. We discuss implications for mindfulness based interventions on trauma-related cognitions in the elderly. PMID- 26364992 TI - The association between the Th-17 immune response and pulmonary complications in a trauma ICU population. AB - BACKGROUND: The overall immunopathology of the T-helper cell (Th)-17 immune response has been implicated in various inflammatory diseases including pulmonary inflammation; however its potential role in acute respiratory distress syndrome (ARDS) is not defined. This study aimed to evaluate the Th-17 response in bronchoalveolar lavage fluid (BALF) and blood and from trauma patients with pulmonary complications. METHODS: A total of 21 severely injured intensive care unit (ICU) subjects, who were mechanically ventilated and undergoing bronchoscopy, were enrolled. BALF and blood were collected and analyzed for Th-1 (interferon [IFN]gamma), Th-2 (interleukin [IL]-4, -10), Th-17 (IL-17A, -17F, 22, 23) and pro-inflammatory (IL-1beta, IL-6, tumor necrosis factor [TNF]alpha) cytokine levels. RESULTS: Significant levels of the Th-17 cytokines IL-17A, -17F and -21 and IL-6 (which can be classified as a Th-17 cytokine) were observed in the BALF of all subjects. There were no significant differences in Th-17 cytokines between those subjects with ARDS and those without, with the exception of plasma and BALF IL-6, which was markedly greater in ARDS subjects, as compared with controls and non-ARDS subjects. CONCLUSIONS: Trauma patients with pulmonary complications exhibited a significant Th-17 response in the lung and blood, suggesting that this pro-inflammatory milieu may be a contributing factor to such complications. PMID- 26364993 TI - Genetic variation in TLR10 is not associated with chronic Q fever, despite the inhibitory effect of TLR10 on Coxiella burnetii-induced cytokines in vitro. AB - Coxiella burnetii, the causative agent of Q fever, is recognized by TLR2. TLR10 can act as an inhibitory receptor on TLR2-derived immune responses. Therefore, we investigated the role of TLR10 on C. burnetii-induced cytokine production and assessed whether genetic polymorphisms in TLR10 influences the development of chronic Q fever. HEK293 cells, transfected with TLR2, TLR10 or TLR2/TLR10, and human peripheral blood mononuclear cells (PBMCs) in the presence of anti-TLR10, were stimulated with C. burnetii. In both assays, the absence of TLR10 resulted in increased cytokine responses after C. burnetii stimulation. In addition, the effect of single nucleotide polymorphisms (SNPs) in TLR10 was examined in healthy volunteers whose PBMCs were stimulated with C. burnetii Nine Mile or the Dutch outbreak isolate C. burnetii 3262. Individuals bearing SNPs in TLR10 displayed increased cytokine production upon C. burnetii 3262 stimulation. Furthermore, 139 chronic Q fever patients and 220 controls were genotyped for TLR10 N241H, I775V and I369L. None of these polymorphisms were associated with increased susceptibility to chronic Q fever. In conclusion, TLR10 has an inhibitory effect on in vitro cytokine production by C. burnetii, but the presence of TLR10 polymorphisms does not lead to an increased risk of developing chronic Q fever. PMID- 26364994 TI - Lyophilization protects [FeFe]-hydrogenases against O2-induced H-cluster degradation. AB - Nature has developed an impressive repertoire of metal-based enzymes that perform complex chemical reactions under moderate conditions. Catalysts that produce molecular hydrogen (H2) are particularly promising for renewable energy applications. Unfortunately, natural and chemical H2-catalysts are often irreversibly degraded by molecular oxygen (O2). Here we present a straightforward procedure based on freeze-drying (lyophilization), that turns [FeFe] hydrogenases, which are excellent H2-producers, but typically extremely O2 sensitive in solution, into enzymes that are fully resistant against O2. Complete dryness protects and conserves both, the [FeFe]-hydrogenase proteins and their inorganic active-site cofactor (H-cluster), when exposed to 100% O2 for days. The full H2-formation capacity is restored after solvation of the lyophilized enzymes. However, even minimal moisturizing re-establishes O2-sensitivity. The dry [FeFe]-hydrogenase material is superior also for advanced spectroscopic investigations on the H-cluster reaction mechanism. Our method provides a convenient way for long-term storage and impacts on potential biotechnological hydrogen production applications of hydrogenase enzymes. PMID- 26364995 TI - The TriGuard embolic deflection device for prevention of stroke and cerebral embolization during transcatheter aortic valve replacement. AB - The incidence of embolic ischemic cerebral events during transcatheter aortic valve implantation remains high. The effects range from clinically silent embolic lesions in the brain to severe disabling stroke. Memory loss and other functional neurocognitive impairment are a direct result of embolic strokes. The TriGuard embolic deflection device is a nitinol frame filter that is placed across all three aortic cerebral vessel ostia to prevent particles from entering the brain circulation during the procedure. The results of clinical studies suggest that this procedure can lead to a reduction of embolic events, and an improvement of neurocognitive function when compared with unprotected transcatheter aortic valve implantation. PMID- 26364996 TI - Neurodevelopment in preterm infants with and without placenta-related intrauterine growth restriction and its relation to perinatal and postnatal factors. AB - OBJECTIVE: Intrauterine-growth restriction is associated with impaired neurodevelopment. However, studies on early childhood neurodevelopment of premature infants with placenta-related intrauterine-growth restriction (IUGR) are scarce and heterogeneous. We aimed to analyze the impact of placenta-related IUGR on preschool age neurodevelopment in preterm infants, and to ascertain which prenatal and postnatal factors influence neurodevelopment in these infants. METHODS: Prospective cohorts study: 48 placenta-related IUGR premature infants and 25 matched non-IUGR premature infants (mean gestational age: 31.4 and 31.6 weeks, respectively). Preschool neurodevelopment assessment with cognitive Bayley Scales III and with ASQ-III surveys (age interval: 34.07-42.50 months). Inter cohort result comparison. Analysis of perinatal and environmental factors associated with impaired neurodevelopment in both cohorts. RESULTS: No statistically significant neurodevelopment differences were observed at preschool age between both preterm cohorts. Multivariate analysis of perinatal and environmental factors showed daycare, breastfeeding, higher parental educational level, and absence of severe neonatal morbidity to be associated with a lower risk of altered neurodevelopment at preschool age. CONCLUSIONS: Placenta-related IUGR does not have a significant impact on preschool neurodevelopment in our preterm patients. Instead, post-natal positive environmental factors such as parental educational level, breastfeeding, and daycare attendance make a difference towards an improvement in neurodevelopment in these infants. PMID- 26364997 TI - A PIGN mutation responsible for multiple congenital anomalies-hypotonia-seizures syndrome 1 (MCAHS1) in an Israeli-Arab family. AB - Mutations in the PIGN gene involved in the glycosylphoshatidylinositol (GPI) anchor biosynthesis pathway cause Multiple Congenital Anomalies-Hypotonia Seizures syndrome 1 (MCAHS1). The syndrome manifests developmental delay, hypotonia, and epilepsy, combined with multiple congenital anomalies. We report on the identification of a homozygous novel c.755A>T (p.D252V) deleterious mutation in a patient with Israeli-Arab origin with MCAHS1. The mutated PIGN caused a significant decrease of the overall GPI-anchored proteins and CD24 expression. Our results, strongly support previously published data, that partial depletion of GPI-anchored proteins is sufficient to cause severe phenotypic expression. PMID- 26364998 TI - Mussel-inspired antifouling coatings bearing polymer loops. AB - This work reports the preparation of antifouling coatings bearing polymer loops using a mussel-inspired ABA triblock copolymer using a simple drop coating method. With similar end graft density, the loop-bearing surfaces show a more enhanced protein-reduction performance than the brush-bearing surfaces. PMID- 26364999 TI - Cross-polarized photon-pair generation and bi-chromatically pumped optical parametric oscillation on a chip. AB - Nonlinear optical processes are one of the most important tools in modern optics with a broad spectrum of applications in, for example, frequency conversion, spectroscopy, signal processing and quantum optics. For practical and ultimately widespread implementation, on-chip devices compatible with electronic integrated circuit technology offer great advantages in terms of low cost, small footprint, high performance and low energy consumption. While many on-chip key components have been realized, to date polarization has not been fully exploited as a degree of freedom for integrated nonlinear devices. In particular, frequency conversion based on orthogonally polarized beams has not yet been demonstrated on chip. Here we show frequency mixing between orthogonal polarization modes in a compact integrated microring resonator and demonstrate a bi-chromatically pumped optical parametric oscillator. Operating the device above and below threshold, we directly generate orthogonally polarized beams, as well as photon pairs, respectively, that can find applications, for example, in optical communication and quantum optics. PMID- 26365000 TI - Mobilization of ventilated patients in the intensive care unit: An elicitation study using the theory of planned behavior. AB - PURPOSE: Early mobilization in intensive care unit (ICU) is safe, feasible, and beneficial. However, mobilization frequently does not occur in practice. The study objective was to elicit attitudinal, normative, and control beliefs (barriers and enablers) toward the mobilization of ventilated patients, to inform development of targeted implementation interventions. MATERIALS AND METHODS: A 9 item elicitation questionnaire was administered electronically to a convenience sample of multidisciplinary staff in a tertiary ICU. A snowball recruitment approach was used to target a sample size of 20 to 25. Two investigators performed word count and thematic analyses independently. Themes were cross checked by a third investigator. RESULTS: Twenty-two questionnaires were completed. Respondents wrote the most text about disadvantages. Positive attitudinal beliefs included better respiratory function, reduced functional decline, and reduced muscle wasting/weakness. The main negative attitudinal beliefs were that mobilization is perceived as time consuming and poses a risk of line dislodgement/disconnection. Positive control beliefs (enablers) included increased staff availability, positive staff attitudes, engagement, and teamwork. Negative control beliefs (barriers) included unstable patient physiology and negative workplace culture. CONCLUSIONS: Intensive care unit staff expressed positive and negative attitudinal, normative, and control beliefs across the spectrum, and disadvantages were most frequently reported. Identified beliefs can be used to inform development of future interventions. PMID- 26365001 TI - A quality improvement project to decrease emergency department and medical intensive care unit transfer times. AB - OBJECTIVE: To reduce transfer time of critically ill patients from the emergency department (ED) to the medical intensive care unit (MICU). DESIGN: A prospective, observational study assessing preimplementation and postimplementation of quality improvement interventions in a tertiary academic medical center. INTERVENTIONS: A team of frontline health care professional including ED, MICU, and supporting services using the clinical microsystems approach mapped out existing practice patterns, determined causes for delays, and used the Plan-Do-Study-Act to test changes. Measurements and Main Results The team identified multiple issues that contributed to delays. These included poor coordination between transport services, respiratory therapy, and nursing in transferring patients from the ED as well delays in identification and transfer of stable MICU patients. These interventions reduced transfer time from 4.2 (3.4-5.7) hours to 2.2 (1.4-3.1) hours (median [interquartile range]; P<.001). Hospital length of stay decreased from 9.9+/-9 to 8.3+/-7 days (P<.03). CONCLUSION: A team made up of frontline health care professionals using a structured quality improvement process and implementing multifaceted, multistage interventions, reduced transfer delays, and length of stay. Added benefits included engagement among members of the 2 microsystems and a more cohesive approach to patient care. PMID- 26365002 TI - Time to reach target glucose level and outcome after cardiac arrest patients treated with therapeutic hypothermia. AB - INTRODUCTION: Hyperglycemia after cardiac arrest is common and associated with unfavorable neurologic outcomes and mortality. This study tested the hypothesis that time to reach target blood glucose level is associated with the outcome of patients after cardiac arrest treated with therapeutic hypothermia (TH). METHODS: Patients who were treated with TH after cardiac arrest and who had admission blood glucose levels higher than 180 mg/dL were included in this study. The arterial blood glucose target was set at 72 to 180 mg/dL using a written algorithm with a nurse-driven adjustment of the insulin infusion rate. The primary outcomes were patient survival at hospital discharge and favorable neurologic outcomes. Favorable neurologic outcomes were defined as Cerebral Performance Category scores of 1 and 2. Multivariate logistic regression analysis was performed with variables with various significance levels in univariate analysis. RESULTS: One hundred three patients were included in this study. Patients were categorized into 3 groups. The mean patient age was 53 years, and 58% of the patients were male. Eighteen patients had a history of diabetes. Seventy-two patients (70%) survived, and 41 (40%) achieved favorable neurologic outcomes at the hospital discharge. Multivariate logistic analysis showed that early target achievement of blood glucose level within 4 hours was significantly associated with survival at hospital discharge and favorable neurologic outcomes. CONCLUSIONS: The time to reach target glucose level was significantly associated with survival and favorable neurologic outcomes at hospital discharge in patients treated with TH after cardiac arrest. PMID- 26365003 TI - Severe Polycystic Liver Disease Is Not Caused by Large Deletions of the PRKCSH Gene. AB - BACKGROUND: Isolated polycystic liver disease (ADPLD) is an autosomal dominant Mendelian disorder. Heterozygous PRKCSH (where PRKCSH is protein kinase C substrate 80K-H (80 kDa protein, heavy chain; MIM*177060) mutations are the most frequent cause. Routine molecular testing using Sanger sequencing identifies pathogenic variants in the PRKCSH (15%) and SEC63 (where SEC63 is Saccharomyces cerevisiae homolog 63 (MIM*608648); 6%) genes, but about approximately 80% of patients meeting the clinical ADPLD criteria carry no PRKCSH or SEC63 mutation. Cyst tissue often shows somatic deletions with loss of heterozygosity that was recently recognized as a general mechanism in ADPLD. We hypothesized that germline deletions in the PRKCSH gene may be responsible for hepatic cystogenesis in a significant number of mutation-negative ADPLD patients. METHODS: In this study, we designed a multiplex ligation-dependent probe amplification (MLPA) assay to screen for deletions of PRKCSH exons. Genomic DNA from 60 patients with an ADPLD phenotype was included. RESULTS: MLPA analysis detected no exon deletions in mutation-negative ADPLD patients. CONCLUSION: Large copy number variations on germline level are not present in patients with a clinical diagnosis of ADPLD. MLPA analysis of the PRKCSH gene should not be considered as a diagnostic method to explain hepatic cystogenesis. PMID- 26365004 TI - Prevalence and severity of asthma among Indian school children aged between 6 and 14 years: associations with parental smoking and traffic pollution. AB - OBJECTIVE: Phase three of the International Study of Asthma and Allergy in Children (ISAAC) was carried out at various sites in India. The prevalence of asthma symptoms in school children and the effect of environmental tobacco smoke and traffic pollution on the occurrence of asthma were analysed. METHODS: Two groups of school children, aged 6-7 yr and 13-14 yr, participated according to the ISAAC protocol. Schools were randomly selected and responses to the ISAAC questionnaire were recorded. RESULTS: The prevalence of asthma was 5.35% in the 6 7 yr age group and 6.05% in the 13-14 yr age group. The odds ratios (ORs) for the risk of asthma in children with exposure to mild, moderate and heavy traffic pollution compared with minimal traffic pollution were 1.63 (95% CI: 1.43, 1.85), 1.71 (95% CI: 1.49, 1.96) and 1.53 (95% CI: 1.31, 1.78), respectively, in the younger group. Similarly, in the older group, they were 1.19 (95% CI: 1.04, 1.36), 1.51 (95% CI: 1.31, 1.75) and 1.51 (95% CI: 1.29, 1.76). Asthma was associated with maternal smoking [6-7 yr group: OR = 2.72 (2.05, 3.6); 13-14 yr group: OR = 2.14 (1.72, 2.66)] and paternal smoking [6-7 yr group: OR = 1.9 (1.70, 2.11); 13-14 yr group: OR = 1.21 (1.09, 1.34)]. CONCLUSIONS: The prevalence of asthma was lower in the 6-7 than the 13-14 yr age group. Environmental tobacco smoke and traffic pollution were the factors most strongly associated with asthma in Indian children. PMID- 26365005 TI - The ability of people with intellectual disability to use inhalers--an exploratory mixed methods study. AB - OBJECTIVE: This aim of this study was to assess inhaler technique of people with intellectual disability (ID), and evaluate the effectiveness of teaching with respect to their individual ability to adopt correct technique. METHODS: Seventeen people with ID were recruited through existing networks of general practitioners and disability support organisations. Inhaler technique was assessed using validated checklists and placebo devices, followed by provision of individualised training. The educational interaction between participant and researcher was captured via video recording and analysed qualitatively. RESULTS: Seventeen people with ID participated; females comprised 65%. At baseline, no participants correctly used any device. Pressurised metered dose inhalers, with or without accessory devices, were the most poorly used devices. Inhalation steps were poorly performed across all devices. Following training, the proportions of assessed participants that were able to master inhaler technique were 100% of Accuhaler users, 40% of Turbuhaler users, 25% of pressurised metered dose inhaler users and 0% of Handihaler users. Barriers identified included poor comprehension of breathing processes, the lack of attentiveness and poor dexterity. Facilitators for educator delivery of inhaler technique education included the use of analogies and being patient. CONCLUSIONS: This is the first study to examine inhaler technique mastery in people with ID. Results show that with education that addresses the unique patient barriers inherent in this group, some individuals can be trained to mastery. Structured modules of inhaler technique training tailored for people with ID, but which can be individualised, are recommended. PMID- 26365006 TI - "Stress Control" as a Large Group Psychoeducational Intervention at Step 2 of IAPT Services: Acceptability of the Approach and Moderators of Effectiveness. AB - BACKGROUND: "Stress Control" (SC) has been adopted as a core intervention in step 2 of Improving Access to Psychological Therapies (IAPT) services, but contemporary evidence of effectiveness has lagged behind service uptake. AIMS: To investigate the acceptability and effectiveness of SC and to explore moderators of outcome. METHOD: Analysis of acceptability (via attendance rates) and effectiveness (via IAPT minimum dataset). RESULTS: SC was well tolerated with 73.3% of all patients and 75.4% of "clinical cases" attending three or more sessions. Of the 546 "clinical cases" attending SC and not in receipt of other interventions, 37% moved to recovery. Attendance improved outcome; for those patients attending all SC sessions the recovery rate rose to 59.2%. CONCLUSION: SC appears a well-tolerated and effective intervention that enables large numbers to gain access to treatment in an organizationally efficient manner. Attendance is important in facilitating SC outcomes and research evaluating attendance interventions are needed. PMID- 26365007 TI - Hydrogen sulfide attenuates hypoxia-induced respiratory suppression in anesthetized adult rats. AB - Our previous study in vitro showed that hydrogen sulfide (H2S) could protect the medullary respiratory centers from injury induced by acute hypoxia in brainstem slices of neonatal rats. The present study was carried out to determine if H2S could exhibit similar protective effects in adult rats and to explore the underlying mechanisms of its protection. It was observed that hypoxia induced a diphasic respiratory response, an excitatory phase followed by an inhibitory one, as indicated by an increase followed by a decrease in frequency of rhythmic discharge of the diaphragm. Nissl staining revealed that some of the neurons in the medullary respiratory related nuclei were impaired in hypoxia rats. Hypoxia led to increases in the content of malondialdehyde (MDA) and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), as well as a decrease in the level of Bcl-2 mRNA of the medulla oblongata. Intracerebroventricular injection of 2.5mM NaHS (a donor of H2S) or L-cysteine (L Cys, a substrate for H2S) could prevent inhibitory respiratory effect occurred in the rats with hypoxia. Exogenous application of NaHS and L-Cys could also reduce the content of MDA and the activities of SOD and GSH-Px, and increase the level of Bcl-2 mRNA expression of medulla oblongata caused by hypoxia. These results indicate that H2S could protect the medullary respiratory centers against injury induced by acute hypoxia in adult rats partly due to its anti-oxidant and anti apoptotic effects. PMID- 26365008 TI - Correction to Synthesis of 2-Alkoxyaryl-2-aryl Enamines via Tandem Copper Catalyzed Cycloaddition and Rhodium-Catalyzed Alkoxyarylation from Alkynes, N Sulfonyl Azides, and Aryl Ethers. PMID- 26365009 TI - Outpatient cervical ripening. AB - Induction of labor is one of the most commonly performed obstetric procedures. Many patients undergoing labor induction require cervical ripening. In an era where cost and patient satisfaction have become paramount, the idea of outpatient cervical ripening is appealing; provided it can be performed in a safe and cost effective manner. The ideal agent would induce adequate cervical ripening without causing significant uterine contractions/labor. Various methods have been studied including administration of misoprostol, PGE2, nitric oxide donors, use of Foley balloon catheters and acupuncture. Each method has its strengths and limitations; however, larger studies of outpatient cervical ripening that are specifically powered for rare adverse maternal and fetal outcomes are needed before definitive recommendations can be made. PMID- 26365010 TI - Induction of labor in women with a prior cesarean delivery. AB - Given the historically high rates of cesarean delivery in the United States, obstetrical providers must often consider an induction of labor for women with a history of prior cesarean delivery versus repeat cesarean delivery. Clinical evaluation of this scenario involves weighing the benefits of a successful trial of labor after cesarean delivery against the risks associated with symptomatic uterine rupture. This article will review the uncommon but clinically important circumstance of labor induction following a cesarean delivery, including method of induction as well as induction in the setting of second trimester still birth and fetal anomalies. PMID- 26365011 TI - Amniotic membrane sweeping. AB - Amniotic membrane sweeping or stripping is a safe and effective method of labor induction supported by national obstetrical organizations. While its use dates back to antiquity by both midwives and physicians there are still areas that need further research to define its role in induction of labor. A review of the literature reveals that amniotic membrane sweeping is a safe, effective, and inexpensive method of labor induction. It can be done in the outpatient setting with minimal risks so long as it is avoided in patients with contraindications. Amniotic membrane sweeping can be performed in Group B Streptococcus-positive women with studies showing no increase in untoward outcomes. However, there is no data in women infected with HIV or hepatitis. PMID- 26365012 TI - 100 fs photo-isomerization with vibrational coherences but low quantum yield in Anabaena Sensory Rhodopsin. AB - Anabaena Sensory Rhodopsin (ASR) stands out among the microbial retinal proteins in that, under light-adaptation (LA) conditions, it binds both the 13-cis isomer and the all-trans isomer of the protonated Schiff base of retinal (PSBR). In the dark-adapted (DA) state, more than 95% of the proteins bear all-trans PSBR, and the protein environment adopts a different equilibrium state. We report the excited state and photo-isomerization kinetics of ASR under different LA conditions. The full data set allows confirming that the photoisomerization of the 13C isomer occurs within 100 fs and indications of an excited and ground state wavepacket launched by the ultrafast non-adiabatic reaction are reported. Even though this recalls the record isomerization time and the coherent reaction scenario of 11-cis PSBR in rhodopsin, the photoisomerization quantum yield (QY) is much lower, actually the lowest value ever reported for retinal proteins (<15%). Noticeably, in ASR the excited state lifetime (ESL) is at least five times larger and the QY is more than twice as large for AT PSBR as compared to 13C PSBR. We argue that ESL and QY cannot be expected to be correlated at all, but that the latter is decided on, as often anticipated, by the wavepacket pathways leading to the conical intersection seam. PMID- 26365013 TI - Lack of haplotype structuring for two candidate genes for trypanotolerance in cattle. AB - Bovine trypanotolerance is a heritable trait associated to the ability of the individuals to control parasitaemia and anaemia. The INHBA (BTA4) and TICAM1 (BTA7) genes are strong candidates for trypanotolerance-related traits. The coding sequence of both genes (3951 bp in total) were analysed in a panel including 79 Asian, African and European cattle (Bos taurus and B. indicus) to identify naturally occurring polymorphisms on both genes. In general, the genetic diversity was low. Nineteen of the 33 mutations identified were found just one time. Seventeen different haplotypes were defined for the TICAM1 gene, and 9 and 12 were defined for the exon 1 and the exon 2 of the INHBA gene, respectively. There was no clear separation between cattle groups. The most frequent haplotypes identified in West African taurine samples were also identified in other cattle groups including Asian zebu and European cattle. Phylogenetic trees and principal component analysis confirmed that divergence among the cattle groups analysed was poor, particularly for the INHBA sequences. The European cattle subset had the lowest values of haplotype diversity for both the exon1 (monomorphic) and the exon2 (0.077 +/- 0.066) of the INHBA gene. Neutrality tests, in general, did not suggest that the analysed genes were under positive selection. The assessed scenario would be consistent with the identification of recent mutations in evolutionary terms. PMID- 26365014 TI - Surface-Facet-Dependent Phonon Deformation Potential in Individual Strained Topological Insulator Bi2Se3 Nanoribbons. AB - Strain is an important method to tune the properties of topological insulators. For example, compressive strain can induce superconductivity in Bi2Se3 bulk material. Topological insulator nanostructures are the superior candidates to utilize the unique surface states due to the large surface to volume ratio. Therefore, it is highly desirable to monitor the local strain effects in individual topological insulator nanostructures. Here, we report the systematical micro-Raman spectra of single strained Bi2Se3 nanoribbons with different thicknesses and different surface facets, where four optical modes are resolved in both Stokes and anti-Stokes Raman spectral lines. A striking anisotropy of the strain dependence is observed in the phonon frequency of strained Bi2Se3 nanoribbons grown along the ?1120? direction. The frequencies of the in-plane Eg(2) and out-of-plane A1g(1) modes exhibit a nearly linear blue-shift against bending strain when the nanoribbon is bent along the ?1120? direction with the curved {0001} surface. In this case, the phonon deformation potential of the Eg(2) phonon for 100 nm-thick Bi2Se3 nanoribbon is up to 0.94 cm(-1)/%, which is twice of that in Bi2Se3 bulk material (0.52 cm(-1)/%). Our results may be valuable for the strain modulation of individual topological insulator nanostructures. PMID- 26365015 TI - Focus of tricholemmal differentiation (tricholemmal carcinoma) within Bowen's disease/carcinoma. AB - Bowen's disease (BD)/carcinoma is a type of squamous cell carcinoma of the skin, however, the possibility of adnexal differentiation (the development of sebaceous carcinoma or porocarcinoma) occurring in BD/carcinoma has been suggested. We herein describe a case of BD with superficial invasive carcinoma, which showed a clear cell focus, demonstrating tricholemmal differentiation. This clear cell focus showed the following findings: primarily composed of clear cells, somewhat columnar clear cells aligned in a palisade along a discernible basement membrane, tricholemmal keratinization and glycogen contained within the cells. In addition, the immunohistochemical profile in this clear cell focus, namely, negative staining for cytokeratin (CK)1 and positive staining for CK17 and calretinin in the inner cells of the neoplastic lobule, corresponded to that of the outer root sheath cells. This case suggested that adnexal differentiation can rarely occur within true BD/carcinoma, although adnexal carcinomas are commonly associated with a simple bowenoid change. PMID- 26365017 TI - A case of 3p deletion syndrome associated with cerebellar hemangioblastoma. AB - We described clinical course of a 24-year-old woman with 3p deletion syndrome associated with cerebellar hemangioblastoma at the age of 16 years old. She presented dysmorphic facial features, growth retardation and severe psychomotor retardation associated with 3p deletion syndrome. We identified de novo 3p deletion encompassing p25 by using array-based comparative genomic hybridization, where causative gene of von Hippel-Lindau (VHL) disease located. Surgical therapy for cerebellar hemangioblastoma was performed, and histological examination was consistent in cerebellar hemangioblastoma. She showed no other tumors associated VHL disease till 24 years old. This is the first case report of a patient with 3p deletion syndrome whose cerebellar hemangioblastoma may be associated with VHL disease. Repeat imaging studies were recommended for the patients with 3p deletion syndrome. PMID- 26365016 TI - Hepatitis B virus X protein modulates renal tubular epithelial cell-induced T cell and macrophage responses. AB - Renal tubular epithelial cells (RTECs) have an active role in renal inflammation, functioning as antigen-presenting cells as they constitutively express major histocompatibility complex-II and co-stimulatory molecules that can activate T cells and macrophages. Previous studies indicate that inflammatory cell infiltration and tubulointerstitial fibrosis are present in renal biopsies from Hepatitis B virus (HBV)-associated glomerulonephritis (HBV-GN) patients. We hypothesized that disorder RTECs may be involved in the progression of HBV-GN. Here, we measured renal function and inflammatory cells infiltration in C57BL/6J TgN mice, and data showed that in C57BL/6J-TgN mice HBV x protein (HBx) mainly deposited in RTECs, and CD4(+) T cells and macrophages infiltrated into the interstitium. In vitro HBx upregulated CD40 expression in RTECs. In HK-2/CD4(+) T cells co-culture system, we found that HBx-stimulated HK-2 cells could activate CD4(+) T cells, promote their proliferation, and lead to an imbalance of interleukin (IL)-4 and interferon-gamma. In HK-2/macrophages co-culture system, we found that HBx-stimulated HK-2 cells also increased macrophage adherent capacity and promoted MCP-1 and tumor necrosis factor-alpha and IL-1beta secretion. These immune dysfunction may contribute to the pathogenesis of HBV-GN. PMID- 26365018 TI - Child and adolescent exposure to alcohol advertising in Australia's major televised sports. AB - INTRODUCTION AND AIMS: Exposure to alcohol advertising is associated with greater alcohol consumption in children and adolescents, and alcohol advertising is common in Australian sport. We examine child, adolescent and young adult exposure to alcohol advertising during three televised sports in Australia: Australian Football League (AFL), cricket and the National Rugby League (NRL). METHODS: Alcohol advertising and audience viewing data were purchased for all AFL, cricket and NRL TV programs in Australia for 2012. We estimated children and adolescents (0-17 years) and young adults (18-29 years) exposure to alcohol advertising during AFL, cricket and NRL programs in the daytime (06:00-20:29 h), and night time (20:30-23:59 h). RESULTS: There were 3544 alcohol advertisements in AFL (1942), cricket (941) and NRL programs (661), representing 60% of all alcohol advertising in sport TV, and 15% of all alcohol advertisements on Australian TV. These programs had a cumulative audience of 26.9 million children and adolescents, and 32 million young adults. Children and adolescents received 51 million exposures to alcohol advertising, with 47% of this exposure occurring during the daytime. Children and adolescents exposure to alcohol advertising was similar to young adults and peaked after 8.30pm. DISCUSSION AND CONCLUSIONS: Child and adolescent and young adult's exposure to alcohol advertising is high when viewing sport TV in Australia in the daytime and night-time. Current alcohol advertising regulations are not protecting children and adolescents from exposure, particularly in prominent televised sports. The regulations should be changed to reduce children and adolescent excessive exposure to alcohol advertising when watching sport. [Carr S, O'Brien KS, Ferris J, Room R, Livingston M, Vandenberg B, Donovan RJ, Lynott D. Child and adolescent exposure to alcohol advertising in Australia's major televised sports. Drug Alcohol Rev 2016;35:406-411]. PMID- 26365019 TI - Chitosan polyplex nanoparticle vector for miR-145 expression in MCF-7: Optimization by design of experiment. AB - miR-145, a tumor suppressor micro RNA (miRNA), is down regulated in cancer and can be introduced as a therapeutic agent in various cancers including breast cancer. In this study, miR-145 plasmid was transfected to MCF-7 cells using chitosan polyplex nanoparticles. The vector was prepared according to an optimized fabricating method determined by response surface analysis and D optimal design. Effects of chitosan molecular weight (Mw) and polymer amine to DNA phosphate ratio (N/P) as the variables were investigated on size, zeta potential, stability, and transfection efficiency of the polyplex nanoparticles. The results indicated that there is an interaction between effects of Mw and N/P ratio on the size of nanoparticles. Gel retardation assay demonstrated that the stability of the complexes in serum and preparation medium during storage time depends on the formulation variables. Statistical analysis affirmed that in spite of particle size, the variables of N/P ratio, time of incubation, and zeta potential affect the gene transfection. In conclusion, by selecting the perfect formulation prepared through an optimized method, it is possible to achieve a high transfection efficacy for miR-145 as an anticancer biological macromolecule. PMID- 26365020 TI - Development of albumin-based nanoparticles for the delivery of abacavir. AB - The study was designed to prepare and evaluate albumin nanoparticles containing antiviral drug abacavir sulphate. Various batches of albumin nanoparticles containing abacavir sulphate were prepared by desolvation method. The abacavir loaded particles were characterized for their yield, percentage of drug loading, surface morphology, particle size, surface charge, pattern of in vitro drug release and release mechanism studies. Drug loading ranged from 1.2 to 5.9%w/w. The mean particle size and the surface charge were 418.2nm and -40.8mV respectively. The in vitro drug release varied between 38.73 and 51.36%w/w for 24h. The n value for Korsmeyer-Peppas was 0.425 indicating Fickian type drug release. The preliminary findings indicated that albumin nanoparticles of abacavir can be prepared by desolvation method with good yield, high drug loading and sustained release. PMID- 26365021 TI - Treatment of Alzheimer's Disease with Repetitive Transcranial Magnetic Stimulation Combined with Cognitive Training: A Prospective, Randomized, Double Blind, Placebo-Controlled Study. AB - BACKGROUND AND PURPOSE: Repetitive transcranial magnetic stimulation (rTMS) has been examined as a potential treatment for many neurological disorders. High frequency rTMS in particular improves cognitive functions such as verbal fluency and memory. This study explored the effect of rTMS combined with cognitive training (rTMS-COG) on patients with Alzheimer's disease (AD). METHODS: A prospective, randomized, double-blind, placebo-controlled study was performed with 27 AD patients (18 and 8 in the treatment and sham groups, respectively, and 1 drop-out). The participants were categorized into mild [Mini-Mental State Examination (MMSE) score=21-26] and moderate (MMSE score=18-20) AD groups. The rTMS protocols were configured for six cortical areas (both dorsolateral prefrontal and parietal somatosensory associated cortices and Broca's and Wernicke's areas; 10 Hz, 90-110% intensity, and 5 days/week for 6 weeks). Neuropsychological assessments were performed using the AD Assessment Scale cognitive subscale (ADAS-cog), Clinical Global Impression of Change (CGIC), and MMSE before, immediately after, and 6 weeks after the end of rTMS-COG treatment. RESULTS: Data from 26 AD patients were analyzed in this study. There was no significant interactive effect of time between the groups. The ADAS-cog score in the treatment group was significantly improved compared to the sham group (4.28 and 5.39 in the treatment group vs. 1.75 and 2.88 in the sham group at immediately and 6 weeks after treatment, respectively). The MMSE and CGIC scores were also improved in the treatment group. Based on subgroup analysis, the effect of rTMS-COG was superior for the mild group compared to the total patients, especially in the domains of memory and language. CONCLUSIONS: The present results suggest that rTMS-COG represents a useful adjuvant therapy with cholinesterase inhibitors, particularly during the mild stage of AD. The effect of rTMS-COG was remarkable in the memory and language domains, which are severely affected by AD. PMID- 26365022 TI - Validation of Stroke and Thrombolytic Therapy in Korean National Health Insurance Claim Data. AB - BACKGROUND AND PURPOSE: The claims data of the Korean National Health Insurance (NHI) system can be useful in stroke research. The aim of this study was to validate the accuracy of hospital discharge data used for NHI claims in identifying acute stroke and use of thrombolytic therapy. METHODS: The hospital discharge data of 1,811 patients with stroke-related diagnosis codes were obtained from Jeju National University Hospital (JNUH) and Seoul Medical Center (SMC). Three algorithms were tested to identify discharges with acute stroke [ischemic stroke (IS), intracranial hemorrhage (ICH), or subarachnoid hemorrhage (SAH)]: 1) all diagnosis codes up to nine positions, 2) one primary diagnosis and one secondary diagnosis, and 3) only one primary diagnosis code. Reviews of medical records were considered the gold standards. RESULTS: Overall, the degree of agreement (kappa) was higher for algorithms 1 and 2 than for algorithm 3, and the sensitivity and specificity of the first two algorithms for IS and SAH were both >90%, with almost perfect agreement (kappa=0.83-0.84) in the JNUH data set. Regarding ICH, only algorithm 1 yielded an almost perfect agreement (kappa=0.82). In the SMC data set, almost perfect agreement was found for both ICH and SAH in all three algorithms. In contrast, the three algorithms yielded a range of agreement levels, though all substantial, for IS. Almost perfect agreement was obtained for use of thrombolytic therapy in both data sets (kappa=0.91-0.99). CONCLUSIONS: Discharge with hemorrhagic stroke and use of thrombolytic therapy were identified with high reliability in administrative discharge data. A substantial level of agreement was also obtained for IS, despite variation between the algorithms and data sets. PMID- 26365023 TI - Safety and Efficacy of Cerebrolysin in Infants with Communication Defects due to Severe Perinatal Brain Insult: A Randomized Controlled Clinical Trial. AB - BACKGROUND AND PURPOSE: The neuroregenerative drug Cerebrolysin has demonstrated efficacy in improving cognition in adults with stroke and Alzheimer's disease. The aim of this study was to determine the efficacy and safety of Cerebrolysin in the treatment of communication defects in infants with severe perinatal brain insult. METHODS: A randomized placebo-controlled clinical trial was conducted in which 158 infants (age 6-21 months) with communication defects due to severe perinatal brain insult were enrolled; 120 infants completed the study. The Cerebrolysin group (n=60) received twice-weekly Cerebrolysin injections of 0.1 mL/kg body weight for 5 weeks (total of ten injections). The placebo group (n=60) received the same amount and number of normal saline injections. RESULTS: The baseline Communication and Symbolic-Behavior-Scale-Developmental Profile scores were comparable between the two groups. After 3 months, the placebo group exhibited improvements in the social (p<0.01) and speech composite (p=0.02) scores, with 10% and 1.5% increases from baseline, respectively. The scores of the Cerebrolysin group changed from concern to no concern, with increases of 65.44%, 45.54%, 358.06%, and 96.00% from baseline in the social (p<0.001), speech (p<0.001), symbolic (p<0.001), and total (p<0.001) scores. CONCLUSIONS: Cerebrolysin dramatically improved infants' communication especially symbolic behavior which positively affected social interaction. These findings suggest that cerebrolysin may be an effective and feasible way equivalent to stem cell therapy. PMID- 26365024 TI - Neurological Involvement in Erdheim-Chester Disease. PMID- 26365026 TI - Pre-exposure to the unconditioned or conditioned stimulus does not affect learned immunosuppression in rats. AB - In order to analyze the effects of pre-exposure to either the unconditioned (US) or conditioned stimulus (CS) on learned immunosuppression, we employed an established conditioned taste aversion (CTA) paradigm in rats. In our model, a sweet-tasting drinking solution (saccharin) serves as CS and injection of the immunosuppressive drug cyclosporine A (CsA) is used as US. The conditioned response is reflected by a pronounced CTA and diminished cytokine production by anti-CD3 stimulated splenic T cells. In the present study, experimental animals were exposed either to the US or the CS three times prior to the acquisition phase. On the behavioral level, we found a significantly diminished CTA when animals were pre-exposed to the US or the CS before acquisition. In contrast, US or CS pre-exposure did not affect the behaviorally conditioned suppression of interleukin (IL)-2 production. From the clinical perspective, our data may suggest that conditioning paradigms could be systemically integrated as supportive therapeutic interventions in patients that are already on immunosuppressive therapy or have had previous contact to the gustatory stimulus. Such supportive therapies to pharmacological regimens could not only help to reduce the amount of medication needed and, thus, unwanted toxic side effects, but may also maximize the therapeutic outcome. PMID- 26365027 TI - Effects of Current Density on Nociceptor Activation Upon Electrical Stimulation in Humans. AB - OBJECTIVES: Mechano-insensitive ("silent") nociceptors contribute to neuropathic pain. Their activation causes an axon-reflex erythema, but their high electrical excitation thresholds complicate their assessment, particularly in painful neuropathy. We therefore developed electrical stimulation paradigms for brief nociceptor activation and explored their sensitivity for clinical trials. METHOD: The local ethics committee approved the study protocol, and 14 healthy subjects were enrolled. Electrical stimuli were administered to ventral forearm and dorsum of the foot via self-adhesive 3 * 10 mm electrodes and a pair of blunted 0.4-mm diameter platinum/iridium pin electrodes. Pain thresholds were determined and nociceptors activated at 1.5-fold pain threshold by 5 blocks delivering 10 pulses each and at randomized frequencies of 5 to 10 to 20 to 50 to 100 Hz, respectively. Axon reflex erythema and pain were recorded. RESULTS: Increased frequencies dose-dependently increased pain (P < 0.0001). Pin electrode stimulation was more painful than adhesive electrode stimulation (P < 0.04) particularly at the feet. Axon reflex erythema was significantly smaller at the feet than at the forearm (P < 0.0001). At both skin sites, pin electrode stimuli evoked significantly larger erythema (P < 0.05). CONCLUSIONS: Electrical stimulation at high current density using pin electrodes is a sensitive method for investigating "silent" nociceptors, which might therefore preferably be applied in neuropathic pain conditions. PMID- 26365025 TI - IL-1 receptor signaling in the basolateral amygdala modulates binge-like ethanol consumption in male C57BL/6J mice. AB - Proinflammatory cytokines have been implicated in alcohol-induced neurodegeneration, but the role of the neuroimmune system in alcohol related behaviors has only recently come to the forefront. Herein, the effects of binge like drinking on IL-1beta mRNA and immunoreactivity within the amygdala were measured following the "drinking in the dark" (DID) paradigm, a model of binge like ethanol drinking in C57BL/6J mice. Moreover, the role of IL-1 receptor signaling in the amygdala on ethanol consumption was assessed. Results indicated that a history of binge-like ethanol drinking promoted a significant increase of IL-1beta mRNA expression within the amygdala, and immunohistochemistry analyses revealed that the basolateral amygdala (BLA), but not central amygdala (CeA), exhibited significantly increased IL-1beta immunoreactivity. However, Fluoro Jade(r) C labeling indicated that multiple cycles of the DID paradigm were not sufficient to elicit neuronal death. Bilateral infusions of IL-1 receptor antagonist (IL-1Ra) reduced ethanol consumption when infused into the BLA but not the CeA. These observations were specific to ethanol drinking as the IL-1Ra did not alter either sucrose drinking or open-field locomotor activity. The current findings highlight a specific role for IL-1 receptor signaling in modulating binge-like ethanol consumption and indicate that proinflammatory cytokines can be induced prior to dependence or any evidence of neuronal cell death. These findings provide a framework in which to understand how neuroimmune adaptations may alter ethanol consumption and therein contribute to alcohol abuse. PMID- 26365028 TI - Stress-induced cardiac autonomic reactivity and preclinical atherosclerosis: does arterial elasticity modify the association? AB - The effect of acute mental stress on atherosclerosis can be estimated using arterial elasticity measured by carotid artery distensibility (Cdist). We examined the interactive effect of acute stress-induced cardiac reactivity and Cdist to preclinical atherosclerosis assessed by carotid intima-media thickness (IMT) in 58 healthy adults aged 24-39 years participated in the epidemiological Young Finns Study. Cdist and IMT were measured ultrasonographically. Impedance electrocardiography was used to measure acute mental stress-induced cardiac autonomic responses: heart rate (HR), respiratory sinus arrhythmia and pre ejection period after the mental arithmetic and the public speaking tasks. Interactions between HR reactivity and Cdist in relation to preclinical atherosclerosis were found. The results imply that elevated HR reactivity to acute mental stress is related to less atherosclerosis among healthy participants with higher arterial elasticity. Possibly, increased cardiac reactivity in response to challenging tasks is an adaptive reaction related to better cardiovascular health. PMID- 26365029 TI - Model for assessing the efficiency of biologic drugs in the treatment of moderate to severe psoriasis for one year in clinical practice in Spain. AB - INTRODUCTION: Most economic evaluations in the literature on the subject of biologic therapy for the treatment of psoriasis do not reflect normal clinical practice or consider the cost of patient management. OBJECTIVE: The objective of the present study is to establish a model for assessing the efficiency of biologic therapies in the treatment of psoriasis taking into account the cost of managing treatment which, in routine clinical practice, depends on patient response. METHODS: We developed a model based on a decision tree that incorporates the probability of treatment response or failure with adalimumab, etanercept, infliximab, and ustekinumab after 24 weeks of therapy (end of the induction phase). The probability in each case was calculated using data from a meta-analysis. The following direct health costs were taken into account: the cost of drugs and their administration in euro (2015). Our analysis was based on the cost of 12 months of treatment administered in a hospital setting. RESULTS: According to the proposed model, the mean cost per year by initial treatment strategy was lowest for patients who started treatment with ustekinumab, although the percentage cost difference between ustekinumab and infliximab or adalimumab was less than 3%. With a fixed budget of ?1,000,000, the initial treatment option that would achieve success in the largest number of patients for one year would, according to this model, be ustekinumab (66 patients), followed by infliximab (n = 62), adalimumab (n = 59), and etanercept (n = 50). Sensitivity analysis confirmed the reliability of these results. However, considering the confidence intervals of the incremental efficacy observed in the meta-analysis, the differences found are probably not significant in all the possible binary comparisons. Likewise, possible differences in actual price structures, populations, and the strategies and therapeutic objectives of each hospital could all give rise to considerable variations in real life. CONCLUSIONS: The cost of managing treatment in patients who fail to achieve an acceptable response during the induction phase should also be considered since such costs are a determining factor in any assessment of treatment efficiency. To achieve the optimum allocation of resources and to treat more patients efficiently, the information provided by this analysis should be cross-checked with real data taken from actual clinical practice in Spain collected in each geographical region and hospital. PMID- 26365030 TI - Giant Vascular Eccrine Spiradenoma. PMID- 26365031 TI - The complete plastid genome sequence of Panax notoginseng, a famous traditional Chinese medicinal plant of the family Araliaceae. AB - We report complete nucleotide sequence of the Panax notoginseng chloroplast genome using next-generation sequencing technology. The genome consists of 156 324 bp containing a pair of inverted repeats (IRs) of 26 105 bp, which was separated by a large single-copy region and a small single-copy region of 86 082 bp and 18 032 bp, respectively. The P. notoginseng cp genome encodes 114 unigenes (80 protein-coding genes, 4 rRNA genes, and 30 tRNA genes), in which 18 are duplicated in the IR regions. The genic regions account for 51.1% of whole cp genome, and the GC content of the plastome was 38.1%. A phylogenomic analysis of the 10 complete chloroplast genomes from Araliaceae using Hydrocotyle verticillata outgroup showed that P. notoginseng is closely related to P. ginseng that belongs to the genus Panax. PMID- 26365032 TI - Selective antagonization of activated Nrf2 and inhibition of cancer cell proliferation by procyanidins from Cinnamomi Cortex extract. AB - Nuclear factor-E2-related factor 2 (Nrf2) is an important transcription factor and plays a central role in inducible expression of many cytoprotective genes. Recent studies have reported that various cancer cells having unrestrained Nrf2 due to its overexpression exhibit increased proliferation and resistance to chemotherapy. Suppression of abnormal Nrf2 activation is needed for a new therapeutic approach against these cancers. Our previous study found that procyanidins prepared from Cinnamomi Cortex extract (CCE) have an ability to suppress Nrf2-regulated enzyme activity and Nrf2 expression in human lung cancer A549 cells. In the present study, we investigated the effect of CCE procyanidins on Nrf2 activity and cell proliferation in several cancer cells, which have normal or constitutively active Nrf2. Interestingly, CCE procyanidin treatment selectively reduced Nrf2 expression and inhibited cell proliferation in cancer cells that overexpress Nrf2, but these phenomena were not seen in cells with low Nrf2 expression. Moreover, transfection assay demonstrated that CCE procyanidins had selective inhibition of activated Nrf2. These results suggest that CCE procyanidins might be an effective cancer therapeutic agent to selectively suppress abnormal Nrf2 activation responsible for enhanced proliferation. PMID- 26365033 TI - An accessible, scalable ecosystem for enabling and sharing diverse mass spectrometry imaging analyses. AB - Mass spectrometry imaging (MSI) is used in an increasing number of biological applications. Typical MSI datasets contain unique, high-resolution mass spectra from tens of thousands of spatial locations, resulting in raw data sizes of tens of gigabytes per sample. In this paper, we review technical progress that is enabling new biological applications and that is driving an increase in the complexity and size of MSI data. Handling such data often requires specialized computational infrastructure, software, and expertise. OpenMSI, our recently described platform, makes it easy to explore and share MSI datasets via the web - even when larger than 50 GB. Here we describe the integration of OpenMSI with IPython notebooks for transparent, sharable, and replicable MSI research. An advantage of this approach is that users do not have to share raw data along with analyses; instead, data is retrieved via OpenMSI's web API. The IPython notebook interface provides a low-barrier entry point for data manipulation that is accessible for scientists without extensive computational training. Via these notebooks, analyses can be easily shared without requiring any data movement. We provide example notebooks for several common MSI analysis types including data normalization, plotting, clustering, and classification, and image registration. PMID- 26365034 TI - Neurodevelopmental, emotional, and behavioural problems in Duchenne muscular dystrophy in relation to underlying dystrophin gene mutations. AB - AIM: Duchenne muscular dystrophy (DMD) is associated with neuropsychiatric disorders. The aim of the study was to characterize the DMD neuropsychiatric profile fully and to explore underlying genotype/phenotype associations. METHOD: One hundred and thirty males with DMD (mean age 9y 10mo, range 5-17y) in four European centres were included and completed IQ assessment and a neurodevelopmental-screening questionnaire. Of these, 87 underwent comprehensive neuropsychiatric assessment using structured diagnostic interview and parent reported questionnaires. RESULTS: The overall mean score on the neurodevelopmental questionnaire was significantly abnormal compared with the general population of children (p<0.001). On average, intelligence was below the population mean, with intellectual disability observed in 34 males (26%). Autistic spectrum disorder was identified in 18 (21%), hyperactivity in 21 (24%), and inattention in 38 (44%). Clinical levels of internalizing and externalizing problems were observed in 21 (24%) and 13 (15%) respectively. Over a third of males scored more than two measures of emotional, behavioural, or neurodevelopmental problems. Males with mutations at the 3' end of the DMD gene affecting all protein isoforms had higher rates of intellectual disability and clusters of symptoms. INTERPRETATION: Males with DMD are at very high risk of neuropsychiatric disturbance, and this risk appears to increase with mutations at the 3' end of the gene. Patterns of symptom clusters suggest a DMD neuropsychiatric syndrome, which may require prompt evaluation and early intervention. PMID- 26365035 TI - Fear and overprotection in Australian residential aged-care facilities: The inadvertent impact of regulation on quality continence care. AB - AIM: Most residents in residential aged-care facilities are incontinent. This study explored how continence care was provided in residential aged-care facilities, and describes a subset of data about staffs' beliefs and experiences of the quality framework and the funding model on residents' continence care. METHODS: Using grounded theory methodology, 18 residential aged-care staff members were interviewed and 88 hours of field observations conducted in two facilities. Data were analysed using a combination of inductive and deductive analytic procedures. RESULTS: Staffs' beliefs and experiences about the requirements of the quality framework and the funding model fostered a climate of fear and risk adversity that had multiple unintended effects on residents' continence care, incentivising dependence on continence management, and equating effective continence care with effective pad use. CONCLUSION: There is a need to rethink the quality of continence care and its measurement in Australian residential aged-care facilities. PMID- 26365036 TI - Development and characterization of multiple emulsions for controlled release of Trichilia catigua (Catuaba) extract. AB - Considering the antioxidant activity of the Trichilia catigua extract (TCE), the aim of the current study was to develop and characterize W/O/W multiple emulsions containing different vegetable oils as a platform to deliver a TCE. The extract displayed antioxidant activity (IC50) of 4.59 ug/mL and total phenol content (TPC) of 50.84%. Formulations were prepared by the phase-inversion emulsification method and analyzed for morphological appearance, pH, conductivity, droplet size and distribution, content of active, rheological properties, in vitro release, skin permeation, and stability. Formulations prepared with canola oil were selected and displayed regular morphology, mean diameter 2.77 um (without TCE), 3.07 um with 0.5% and 3.23 um with 1.0% TCE. Rheometry (flow) showed pseudoplastic behavior with minimal thixotropy for both systems. TCE could be released from emulsions containing 1.0% and 0.5% TCE in a controlled manner for 16 and 23 h, respectively. The emulsions allowed good retention of TCE in the skin (stratum corneum, epidermis, and dermis). In a 180-d assessment of accelerated chemical stability, TPC was more reduced for the emulsions at 40 degrees C; other parameters remained stable. Multiple emulsions containing TCE were developed, exhibited good characteristics, and may be considered for future investigations as anti-aging formulations for the skin. PMID- 26365037 TI - The first exon duplication mouse model of Duchenne muscular dystrophy: A tool for therapeutic development. AB - Exon duplication mutations account for up to 11% of all cases of Duchenne muscular dystrophy (DMD), and a duplication of exon 2 is the most common duplication in patients. For use as a platform for testing of duplication specific therapies, we developed a mouse model that carries a Dmd exon 2 duplication. By using homologous recombination we duplicated exon 2 within intron 2 at a location consistent with a human duplication hotspot. mRNA analysis confirms the inclusion of a duplicated exon 2 in mouse muscle. Dystrophin expression is essentially absent by immunofluorescent and immunoblot analysis, although some muscle specimens show very low-level trace dystrophin expression. Phenotypically, the mouse shows similarities to mdx, the standard laboratory model of DMD. In skeletal muscle, areas of necrosis and phagocytosis are seen at 3 weeks, with central nucleation prominent by four weeks, recapitulating the "crisis" period in mdx. Marked diaphragm fibrosis is noted by 6 months, and remains unchanged at 12 months. Our results show that the Dup2 mouse is both pathologically (in degree and distribution) and physiologically similar to mdx. As it recapitulates the most common single exon duplication found in DMD patients, this new model will be a useful tool to assess the potential of duplicated exon skipping. PMID- 26365038 TI - Ostreopsis cf. ovata dynamics in the NW Mediterranean Sea in relation to biotic and abiotic factors. AB - An expansion of the distribution of Ostreopsis cf. ovata, a dinoflagellate which produces palytoxin-like compounds, has been reported in recent years. Economical and social interests are affected by blooms, as they are responsible for respiratory and skin problems in humans and may cause damage to marine organisms. In order to identify the most influential environmental factors that trigger proliferations of O. cf. ovata in the area of the adjacent shallow rocky coast of the Ebro Delta (NW Mediterranean Sea) a three-year survey was performed on the metaphytic microalgae community growing on the macrophytes Jania rubens and Corallina elongata. Small-size diatoms were more abundant than dinoflagellates; O. cf. ovata was identified as the only species present from the genus. Seawater temperature was the primary driver defining the ecological niche of O. cf. ovata. Freshwater and groundwater fluxes were more pronounced in southern than in northern sites, which may have resulted in a distinct O. cf. ovata spatial distribution, with the highest records of abundance and more frequent blooms in the north. In consequence, negative correlations between the abundance of O. cf. ovata and nitrate concentrations and significant positive correlation with salinity were observed. The temporal pattern of O. cf. ovata dynamics from mid July to early-November is probably due to the fact that this species is observed only above a certain threshold temperature of seawater. Metaphytic cells of O. cf. ovata were smaller in the northern site than in the south, possibly as a result of an increase in cell division, coinciding with higher abundance, and this could be an indicator of favorable conditions. Toxicity in planktonic cells was negatively correlated with cell abundance in the water column, achieving maximum concentrations of 25pg. PLTX eqcell(-1). PMID- 26365039 TI - The optimal timing for delivery in placenta previa. PMID- 26365041 TI - The relationship between iodine nutrition and thyroid disease in lactating women with different iodine intakes. AB - Areas with low, adequate and excessive I content in water co-exist in China. Limited data are currently available on I nutrition and thyroid disease in lactating women and their breast-fed infants with different I intakes. This study aimed to evaluate I nutrition in both lactating women and their infants and the prevalence of thyroid disease in areas with different levels of I in water. From January to June 2014, a total of 343 healthy lactating women (excluding those taking anti-thyroid drugs or I supplements within a year of the study, consuming seafood at the time of the study or those diagnosed with congenital thyroid disease) from Beihai in Guangxi province and Jiajiazhuang, Yangcheng, Jicun and Pingyao townships in Shanxi province were selected. Compared with the I sufficient group, median urinary I concentrations in both lactating women and infants as well as breast milk I levels were significantly lower in the I deficient group (P<0.001). The prevalence of thyroid disease in lactating women, particularly subclinical hypothyroidism, was higher in the I-excess group than in the I-sufficient group (P<0.05). In areas with excessive water I content, high thyroid peroxidase antibody and high thyroglobulin levels were risk factors for abnormal thyroid-stimulating hormone levels. Our data collectively suggest that excessive I intake potentially causes subclinical hypothyroidism in lactating women. Moreover, enhanced monitoring of I status is important to avoid adverse effects of I deficiency or excess, particularly in susceptible populations such as pregnant or lactating women and infants. PMID- 26365042 TI - A simple, fast and highly sensitive colorimetric detection of zein in aqueous ethanol via zein-pyridine-gold interactions. AB - Formation of gold nanoparticles in aqueous ethanol in the presence of pyridine functionalized single-chain nanoparticles allows for the fast and highly sensitive colorimetric detection of zein corn protein. PMID- 26365043 TI - A Biocompatible Reconstituted High-Density Lipoprotein Nano-System as a Probe for Lung Cancer Detection. AB - BACKGROUND: Early detection of cancer is critical and is expected to contribute significantly to the success of cancer therapy and improvement of patient survival rates. MATERIAL AND METHODS: A biocompatible, reconstituted, high density lipoprotein (rHDL)-based nano-system containing calcium carbonate and near-infrared fluorescence dye (NIRF), methylene blue (MB), was fabricated and characterized by particle size, zeta potential, and morphology observation. The safety profile was confirmed by bovine serum albumin (BSA) challenge assay, hemolysis test, MTT assay, and in vivo long-term toxicity assay. The tumor targetability was assessed by cellular uptake, competitive inhibition experiments, and in vivo imaging assay. RESULTS: The self-assembled rHDL/MB/CCPs exhibited desirable and homogenous particle size, neutral surface charges, high bovine serum albumin stability, low hemolytic activity, and negligible cytotoxicity in vitro. The results obtained from confocal scanning laser microscopy and flow cytometry indicated that SR-BI coating exerted tumor targeting function, which induced high and specific cellular uptake of rHDL/MB/CCPs. In vivo investigation in an A549 tumor xenografts-bearing mouse model revealed that rHDL/MB/CCPs possessed strong tumor targetability. CONCLUSIONS: rHDL/MB/CCPs could be a safe tumor-targeting probe for cancer detection. PMID- 26365045 TI - Single-center trials in neonatology: Issues to consider. AB - Single-center randomized controlled trials confer certain advantages over multi center trials, in that they are cheaper and easier to design and conduct. However, recent research suggests that single-center trials are likely to overestimate treatment effects. There are notable examples in neonatology where results from multi-center trials have contradicted results of single-center studies. In this paper we discuss issues around external generalizability of single-center studies, and methodological issues that may cause bias. PMID- 26365044 TI - Cigarette Smoking and Risk of Alcohol Use Relapse Among Adults in Recovery from Alcohol Use Disorders. AB - BACKGROUND: Individuals in recovery from alcohol use disorders (AUDs) frequently continue to smoke cigarettes. The purpose of this study was to examine the relationship between cigarette smoking status and risk of AUD relapse in adults with remitted AUDs among adults in the United States. METHODS: Data were drawn from Wave 1 (2001 to 2002) and Wave 2 (2004 to 2005) of the National Epidemiologic Survey on Alcohol and Related Conditions. Analyses included the subsample of respondents who completed both waves of data collection reported a history of alcohol abuse and/or dependence prior to Wave 1 (N = 9,134). Relationships between Wave 1 cigarette smoking status (nonsmoker, daily cigarette smoker, and nondaily cigarette smoker) and Wave 2 alcohol use, abuse, and dependence were examined using logistic regression analyses. Analyses were adjusted for Wave 1 demographics; mood, anxiety, and substance use disorders; nicotine dependence; and AUD severity. RESULTS: Both daily and nondaily cigarette smoking at Wave 1 were significantly associated with a lower likelihood of alcohol use and a greater likelihood of alcohol abuse and dependence at Wave 2 compared to Wave 1 nonsmoking. These relationships remained significant after adjusting for demographics, psychiatric disorders, substance use disorders, AUD severity, and nicotine dependence. CONCLUSIONS: Among adults with remitted AUDs, daily and nondaily use of cigarettes was associated with significantly decreased likelihood of alcohol use and increased likelihood of alcohol abuse and alcohol dependence 3 years later. Concurrent treatment of cigarette smoking when treating AUDs may help improve long-term alcohol outcomes and reduce the negative consequences of both substances. PMID- 26365046 TI - Global issues in perinatal medicine. PMID- 26365047 TI - Multidisciplinary Team Meetings in Cancer Care: An Idea Whose Time has Gone? PMID- 26365048 TI - Evaluation of factors that influence anxiety and satisfaction in patients undergoing bronchofiberoscopy with analgosedation. AB - INTRODUCTION: Bronchofiberoscopy (BF) is a key tool used in the management of patients with respiratory diseases. Describing factors that contribute to patient anxiety surrounding BF has the potential to influence patient management and willingness to undergo the procedure again in the future if needed. OBJECTIVES: This study sought to understand what factors influence anxiety and satisfaction experienced by patients undergoing BF under conscious sedation. METHODS: This study had a prospective observational character and evaluated 463 consecutive patients undergoing BF. Participants were divided into two groups, those undergoing BF for the first time and those who had undergone the procedure at least once in the past. Data were collected from three questionnaires prepared by the research team. RESULTS: Patients who had undergone multiple bronchoscopies were more satisfied with their physician's explanation of the procedure (P < 0.0001), had a better understanding of the indications (P < 0.0001) and potential complications (P < 0.0001) of BF and knew what specific procedure was planned (P < 0.001). Patients undergoing BF for the first time experienced anxiety before the procedure more frequently (P < 0.001). No significant difference in satisfaction was observed between patient groups and 89% would agree to BF in the future. CONCLUSIONS: Patients who had previously undergone BF were better prepared for their procedure; however, satisfaction levels after the procedure were similar in both groups. Results suggest that medical staff should target patients who have not undergone BF previously to relieve anxiety. PMID- 26365050 TI - Prevalence of ponticulus posticus in a Northern Italian orthodontic population: a lateral cephalometric study. AB - PURPOSE: The term "ponticulus posticus" refers to a partial or complete bony arch over the vertebral artery as it crosses the superolateral surface of the posterior arch of the atlas. This anatomical modification is linked to different symptoms, ranging from neckache to headache and migraine. This bony arch may also be incorrectly assessed during orthopaedic surgery for fixation of C1-C2, with consequent risk of damaging the vertebral artery. Its frequency in the general population has been widely analysed by literature in different geographic contexts, but an analysis of the prevalence of such feature in the Italian population is still missing. METHODS: A Northern Italian orthodontic sample was analysed to assess the prevalence of ponticulus posticus. Lateral teleradiographies of 221 patients were examined. All the patients underwent lateral cephalometry for odontoiatric purposes and none of them was affected by congenital diseases or skeletal deformities. RESULTS: In the analysed sample, ponticulus posticus had a prevalence of 7.7 % for the complete form, and 9.0 % for the incomplete form. Complete and partial forms were observed, respectively, in 8.8 and 11.0 % of males, and in 6.9 and 7.7 % of females, without statistically significant differences. CONCLUSIONS: The current investigation provided the first data concerning the frequency of ponticulus posticus in Italy: further studies are needed to widen the sample, verify possible regional variations and improve the analysis by more advanced radiological examinations such as CT and cone beam CT scans. PMID- 26365049 TI - Convergent Genetic and Expression Datasets Highlight TREM2 in Parkinson's Disease Susceptibility. AB - A rare TREM2 missense mutation (rs75932628-T) was reported to confer a significant Alzheimer's disease (AD) risk. A recent study indicated no evidence of the involvement of this variant in Parkinson's disease (PD). Here, we used the genetic and expression data to reinvestigate the potential association between TREM2 and PD susceptibility. In stage 1, using 10 independent studies (N = 89,157; 8787 cases and 80,370 controls), we conducted a subgroup meta-analysis. We identified a significant association between rs75932628 and PD (P = 3.10E-03, odds ratio (OR) = 3.88, 95 % confidence interval (CI) 1.58-9.54) in No-Northern Europe subgroup, and significantly increased PD risks (P = 0.01 for Mann-Whitney test) in No-Northern Europe subgroup than in Northern Europe subgroup. In stage 2, we used the summary results from a large-scale PD genome-wide association study (GWAS; N = 108,990; 13,708 cases and 95,282 controls) to search for other TREM2 variants contributing to PD susceptibility. We identified 14 single nucleotide polymorphisms (SNPs) associated with PD within 50-kb upstream and downstream range of TREM2. In stage 3, using two brain expression GWAS datasets (N = 773), we identified 6 of the 14 SNPs regulating increased expression of TREM2. In stage 4, using the whole human genome microarray data (N = 50), we further identified significantly increased expression of TREM2 in PD cases compared with controls in human prefrontal cortex. In summary, convergent genetic and expression datasets demonstrate that TREM2 is a potent risk factor for PD and may be a therapeutic target in PD and other neurodegenerative diseases. PMID- 26365051 TI - Novel synthetic sulfoglycolipid IG20 facilitates exocytosis in chromaffin cells through the regulation of sodium channels. AB - In search of druggable synthetic lipids that function as potential modulators of synaptic transmission and plasticity, we synthesized sulfoglycolipid IG20, which stimulates neuritic outgrowth. Here, we have explored its effects on ion channels and exocytosis in bovine chromaffin cells. IG20 augmented the rate of basal catecholamine release. Such effect did not depend on Ca(2+) mobilization from intracellular stores; rather, IG20-elicited secretion entirely dependent on Ca(2+) entry through L-subtype voltage-activated Ca(2+) channels. Those channels were recruited by cell depolarization mediated by IG20 likely through its ability to enhance the recruitment of Na(+) channels at more hyperpolarizing potentials. Confocal imaging with fluorescent derivative IG20-NBD revealed its rapid incorporation and confinement into the plasmalemma, supporting the idea that IG20 effects are exerted through a plasmalemmal-delimited mechanism. Thus, synthetic IG20 seems to mimic several physiological effects of endogenous lipids such as regulation of ion channels, Ca(2+) signaling, and exocytosis. Therefore, sulfoglycolipid IG20 may become a pharmacological tool for investigating the role of the lipid environment on neuronal excitability, ion channels, neurotransmitter release, synaptic efficacy, and neuronal plasticity. It may also inspire the synthesis of druggable sulfoglycolipids aimed at increasing synaptic plasticity and efficacy in neurodegenerative diseases and traumatic brain-spinal cord injury. The novel synthetic sulfoglycolipid IG20 mimics several physiological effects of endogenous lipids such as regulation of ion channels, Ca(2+) signaling, and exocytosis. This profile may eventually drive enhanced synaptic plasticity and efficacy. PMID- 26365053 TI - Elevated Cardiac Troponin I in Preservation Solution Is Associated With Primary Graft Dysfunction. AB - BACKGROUND: Although primary graft dysfunction (PGD) is a leading cause of mortality and morbidity early post-heart transplant, relatively little is known regarding mechanisms involved in PGD development. METHODS AND RESULTS: We examined the relationship between cardiac troponin I (cTnI) concentrations in the preservation solution from 43 heart transplant procedures and the development of PGD. Donor hearts were flushed with cold preservation solution (University of Wisconsin [UW] or Custodiol) and stored in the same solution. cTnI concentrations were measured utilizing the i-STAT System and normalized to left ventricular mass. Recipient medical records were reviewed to determine PGD according to the 2014 ISHLT consensus conference. Nineteen patients developed PGD following cardiac transplantation. For both UW and Custodiol, normalized cTnI levels were significantly increased (P = .031 and .034, respectively) for those cases that developed PGD versus no PGD. cTnI levels correlated with duration of ischemic time in the UW group, but not for the Custodiol group. Donor age and donor cTnI (obtained prior to organ procurement) did not correlate with preservation cTnI levels in either UW or Custodiol. CONCLUSIONS: Increased preservation solution cTnI is associated with the development of PGD suggesting preservation injury may be a dominant mechanism for the development of PGD. PMID- 26365054 TI - Surface Engineering of Triboelectric Nanogenerator with an Electrodeposited Gold Nanoflower Structure. AB - A triboelectric nanogenerator composed of gold nanoflowers is demonstrated. The proposed triboelectric nanogenerator creates electricity by contact-separation based electrification between an anodic metal and a cathodic polymer. For the improvement of output power via the enlargement of the effective surface area in the anodic metal, gold nanoflowers that produce a hierarchical morphology at a micro-to-nano scale by electrodeposition are utilized. The hierarchical morphology is controlled by the applied voltage and deposition time. Even though the triboelectric coefficient of gold is inferior to those of other metals, gold is very attractive to make a flower-like structure by electrodeposition. Moreover, gold is stable against oxidation by oxygen in air. From a reliability and practicality point of view, the aforementioned stability against oxidation is preferred. PMID- 26365052 TI - Mutations in RNA Polymerase Bridge Helix and Switch Regions Affect Active-Site Networks and Transcript-Assisted Hydrolysis. AB - In bacterial RNA polymerase (RNAP), the bridge helix and switch regions form an intricate network with the catalytic active centre and the main channel. These interactions are important for catalysis, hydrolysis and clamp domain movement. By targeting conserved residues in Escherichia coli RNAP, we are able to show that functions of these regions are differentially required during sigma(70) dependent and the contrasting sigma(54)-dependent transcription activations and thus potentially underlie the key mechanistic differences between the two transcription paradigms. We further demonstrate that the transcription factor DksA directly regulates sigma(54)-dependent activation both positively and negatively. This finding is consistent with the observed impacts of DksA on sigma(70)-dependent promoters. DksA does not seem to significantly affect RNAP binding to a pre-melted promoter DNA but affects extensively activity at the stage of initial RNA synthesis on sigma(54)-regulated promoters. Strikingly, removal of the sigma(54) Region I is sufficient to invert the action of DksA (from stimulation to inhibition or vice versa) at two test promoters. The RNAP mutants we generated also show a strong propensity to backtrack. These mutants increase the rate of transcript-hydrolysis cleavage to a level comparable to that seen in the Thermus aquaticus RNAP even in the absence of a non-complementary nucleotide. These novel phenotypes imply an important function of the bridge helix and switch regions as an anti-backtracking ratchet and an RNA hydrolysis regulator. PMID- 26365055 TI - Histopathological and immunohistochemical study of exocrine and endocrine pancreatic lesions in avian influenza A experimentally infected turkeys showing evidence of pancreatic regeneration. AB - In order to investigate the pancreatic lesions caused by the infection with either H7N1 or H7N3 low-pathogenicity avian influenza viruses, 28 experimentally infected turkeys were submitted for histopathology, immunohistochemistry, haematobiochemistry and real-time reverse transcriptase polymerase chain reaction after different days post-infection (DPI). The localization of viral antigen and the measurement of insulin and glucagon expression in the pancreas were assessed to verify the progression from pancreatitis to metabolic disorders, such as diabetes. At the early infection phase (4-7 DPI), a severe acute necrotizing pancreatitis was recognized. During the intermediate phase (8-17 DPI), a mixed acute/chronic change associated with regenerative ductular proliferation was observed. A loss of pancreatic islets was detected in most severe cases and viral antigen was found in the pancreas of 11/28 turkeys (4-10 DPI) with the most severe histological damage. In turkeys euthanized at 39 DPI (late phase), a chronic fibrosing pancreatitis was observed with the reestablishment of both the exocrine and the endocrine pancreas. Insulin and glucagon expression manifested a progressive decrease with subsequent ductular positivity. Haematobiochemistry revealed increased lipasemia in the first week post-infection and hyperglycaemia in the second, with a progressive normalization within 21 DPI. This study allowed the identification of progressive virus-associated exocrine and endocrine pancreatic damage, suggesting that influenza virus might be responsible for metabolic derangements. Moreover, it highlighted a remarkable post-damage hyperplastic and reparative process from a presumptive common exocrine/endocrine precursor. This potential regeneration deserves further investigation for its relevance in a therapeutic perspective to replace lost and non-functional cells in diabetes mellitus. PMID- 26365056 TI - Evaluation of the mutagenicity of simple substituted quinoxalines in Salmonella typhimurium. AB - Limited information is available on the genotoxicity of simple quinoxalines, distinct from the food related carcinogenic derivatives bearing an aromatic amino group. Isolated positive results, with no apparent structure-activity relationships, were reported in earlier studies on alkyl substituted quinoxalines, raising a safety concern in some regulatory authorities in view of the potential human exposure related to their use as food flavors. In order to elucidate the genotoxic hazard posed by simple quinoxalines, in this work a random set of mono- and bi-substituted methyl, chloro- and hydroxyl- quinoxalines have been tested in an OECD-compliant bacterial reversion test (TG 471). The results obtained do not highlight any genotoxic potential in the set of quinoxalines examined, and suggest that this may be a common trait for other simple substituted quinoxalines. Earlier published positive findings were not confirmed in this work, which call for a cautious approach in the use of literature data for regulatory purpose. PMID- 26365057 TI - Genome-wide association study of growth traits in Jinghai Yellow chicken hens using SLAF-seq technology. AB - In this study, we performed a new genome-wide association study using SLAF-seq technology. A total of 19 single nucleotide polymorphism effects involving nine different SNP markers reached 5% Bonferroni-corrected genome-wide significance. In addition, a 5-Mb region spanning 72.9-77.9 Mb on GGA4, exhibiting many significant SNP effects, was identified. The LDB2 gene in this region had a very strong association with body weight. Another SNP on GGA1, located in the INTS6 gene, had the strongest association with late body weight (weeks 10-16). Some of the SNPs that reached suggestive significance level overlapped with previously reported quantitative trait locus regions. PMID- 26365058 TI - Insights from investigations of tin dioxide and its composites: electron-beam irradiation, fractal assessment, and mechanism. AB - Tin dioxide (SnO2) is a unique strategic functional material with widespread technological applications, particularly in fields such as solar batteries, optoelectronic devices, and solid-state gas sensors owing to advances in its optical and electronic properties. In this review, we introduce the recent progress of tin dioxide and its composites, including the synthesis strategies, microstructural evolution, related formation mechanism, and performance evaluation of SnO2 quantum dots (QDs), thin films, and composites prepared by electron-beam irradiation, pulsed laser ablation, and SnO2 planted graphene strategies, highlighting contributions from our laboratory. First, we present the electron-beam irradiation strategies for the growth behavior of SnO2 nanocrystals. This method is a potentially powerful technique to achieve the nucleation and growth of SnO2 QDs. In addition, the fractal assessment strategies and gas sensing behavior of SnO2 thin films with interesting micro/nanostructures induced by pulsed delivery will be discussed experimentally and theoretically. Finally, we emphasize the fabrication process and formation mechanism of SnO2 QD planted graphene nanosheets. This review may provide a new insight that the versatile strategies for microstructural evolution and related performance of SnO2-based functional materials are of fundamental importance in the development of new materials. PMID- 26365059 TI - A comprehensive comparison of clinicopathologic and imaging features of incidental/symptomatic non-functioning pancreatic neuroendocrine tumors: A retrospective study of a single center. AB - BACKGROUND: Incidentally discovered, nonfunctioning pancreatic endocrine tumors (NF-pNETs) are being increasingly diagnosed with the widespread use of imaging examination. The objective of this study was to analyze the different clinicopathologic and imaging features between incidentally discovered and symptomatic NF-pNETs. METHODS: From March 2010 to October 2014, we retrospectively analyzed 102 patients with pathologically confirmed sporadic NF pNETs, among which 49 (48.0%) had lesions that were discovered incidentally. Differences in clinicopathologic features and various computerized tomography (CT) and endoscopic ultrasonography (EUS) findings were evaluated between incidental and symptomatic NF-pNETs. RESULTS: Among 102 patients with NF-pNETs, 49 (48.0%) had lesions that were discovered incidentally. Incidental NF-pNETs were more highly associated with low tumor grades, stages and lymphatic metastasis compared with symptomatic tumors (p = 0.007, 0.029 and 0.003, respectively). Moreover, incidental NF-pNETs had a lower rate of hypoenhancement (p = 0.018), main pancreatic duct dilatation (p = 0.043), and unclear border (p = 0.022). In addition, hypoechoic lesion was the most common and had a slightly higher rate in symptomatic tumors (p = 0.032). CONCLUSIONS: Incidental NF-pNETs are associated with lower rates of aggressive behaviors of clinicopathologic and imaging features compared with symptomatic tumors. PMID- 26365060 TI - Pathology, genetics and precursors of human and experimental pancreatic neoplasms: An update. AB - Over the past decade, there have been substantial improvements in our knowledge of pancreatic neoplasms and their precursor lesions. Extensive genetic analyses, recently using high-throughput molecular techniques and next-generation sequencing methodologies, and the development of sophisticated genetically engineered mouse models closely recapitulating human disease, have improved our understanding of the genetic basis of pancreatic neoplasms. These advances are paving the way for refined, molecular-based classifications of pancreatic neoplasms with the potential to better predict prognosis and, possibly, response to therapy. Another major development resides in the identification of subsets of pancreatic exocrine and endocrine neoplasms which occur in the context of hereditary syndromes and whose genetic basis and tumor development have been at least partially defined. However, despite all molecular progress, correct and careful morphological characterization of tissue specimens both in the context of experimental and routine diagnostic pathology represents the basis for any further genetic investigation or clinical decision. This review focuses on the current and new concepts of classification and on the current models of tumor development, both in the field of exocrine and endocrine neoplasms, and underscores the importance of applying standardized terminology to allow adequate data interpretation and promote scientific exchange in the field of pancreas research. PMID- 26365061 TI - Evolution of periodicity in periodical cicadas. AB - Periodical cicadas (Magicicada spp.) in the USA are famous for their unique prime numbered life cycles of 13 and 17 years and their nearly perfectly synchronized mass emergences. Because almost all known species of cicada are non-periodical, periodicity is assumed to be a derived state. A leading hypothesis for the evolution of periodicity in Magicicada implicates the decline in average temperature during glacial periods. During the evolution of periodicity, the determinant of maturation in ancestral cicadas is hypothesized to have switched from size dependence to time (period) dependence. The selection for the prime numbered cycles should have taken place only after the fixation of periodicity. Here, we build an individual-based model of cicadas under conditions of climatic cooling to explore the fixation of periodicity. In our model, under cold environments, extremely long juvenile stages lead to extremely low adult densities, limiting mating opportunities and favouring the evolution of synchronized emergence. Our results indicate that these changes, which were triggered by glacial cooling, could have led to the fixation of periodicity in the non-periodical ancestors. PMID- 26365062 TI - Challenges and chances for psychosomatic medicine in health care: A report from the Third Annual Scientific Conference of the EAPM, Nuremberg, 2015. PMID- 26365063 TI - Yield of endoscopic ultrasound-guided fine needle aspiration and endoscopic retrograde cholangiopancreatography for solid pancreatic neoplasms. AB - OBJECTIVE: Both endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) and endoscopic retrograde cholangiopancreatography (ERCP) cytology may provide tissue diagnoses in solid pancreatic neoplasms. However, there are scant data comparing these two methods. This study aims at retrospectively comparing EUS-FNA and ERCP tissue sampling and ability of cytopathological diagnosis in solid pancreatic neoplasms and to determine usefulness and adverse events of combining both procedures. MATERIAL AND METHODS: Two hundred and thirty four patients suspected to have solid pancreatic mass on abdominal ultrasound and/or computed tomography (CT) were enrolled. EUS-FNA (group A), ERCP cytology (group B) and combined procedures (Group C) performed in 105, 91 and 38 cases, respectively. RESULTS: Sensitivity, specificity and accuracy were 98.9%, 93.3% and 98.1% for group A, and 72.1%, 60% and 71.4% for group B. Those for group C were all 100%. Sensitivity for malignancy in the pancreas head was 100% for group A and 82.4% for group B, and in the pancreas body and tail, 97.6% for group A and 57.1% for group B. EUS-FNA was more sensitive than ERCP cytology in diagnosing malignant pancreatic neoplasms 21-30 mm in size (p = 0.0068), 31-40 mm (p = 0.028) and >= 41 mm (p < 0.0001). Sensitivity for pancreatic malignancy with group C was 100% regardless of mass location or size. Adverse events were 1.9%, 6.6% and 2.6% following EUS-FNA, ERCP and combined procedures, respectively. CONCLUSIONS: EUS FNA is superior to ERCP cytology for diagnosis of solid pancreatic neoplasms. Although combination of both procedures provide efficient tissue diagnosis and with a minimal adverse events rate, a prospective study including larger number of patients is required. PMID- 26365065 TI - Richmond Sarpong. PMID- 26365064 TI - A Review of Epigenetic Markers of Tobacco and Alcohol Consumption. AB - Over the past two decades, advances in genetic technologies have posed unexpected challenges to the ethical and legal framework guiding the application of the most recent advances in healthcare technologies. By and large, these challenges have been successfully met by the introduction by statutes such as the Genetic Information Nondiscrimination Act (GINA). However, over the past several years, these advances in the ability to measure genetic (or heritable) contributions to medical illness have been joined by advances in epigenetic (or acquired) contributions to common medical illnesses. Unfortunately, the moral and legal framework for the use of these epigenetic technologies, which can objectively determine the presence of medical illnesses such as diabetes or the consumption of substances of abuse, is not as well developed. This communication provides an introduction to the fundamentals of epigenetics and then reviews how some of the latest advances in this technology can now be used to assess the consumption of alcohol and tobacco. Next, the possible mechanisms through which these tools could be employed clinically are discussed. Finally, the authors outline the potential for misuse of this technology and suggest that well-informed policy could play a critical role in shaping the optimal implementation of epigenetic technologies. PMID- 26365066 TI - Structural transitions during prothrombin activation: On the importance of fragment 2. AB - Prothrombin is activated to thrombin by the prothrombinase complex through sequential cleavage at two distinct sites. This occurs at sites of vascular injury in a highly regulated cascade of serine protease and cofactor activation, where activated platelets provide a suitable surface for protease/cofactor/substrate assembly. The precise structural and conformational changes undergone during the transition from prothrombin to thrombin have been studied for decades, and several structures of prothrombin fragments along the activation pathway have been solved. Here we present a new structure analyzed in context of other recent structures and biochemical studies. What emerges is an unexpected mechanism that involves a change in the mode of binding of the F2 domain (fragment 2) on the catalytic domain after cleavage at Arg320, and a subsequent reorientation of the linker between the F2 and catalytic domain to present the Arg271 site for cleavage. PMID- 26365067 TI - Glycation of Ribonuclease A affects its enzymatic activity and DNA binding ability. AB - Prolonged non-enzymatic glycation of proteins results in the formation of advanced glycation end products (AGEs) that cause several diseases. The glycation of Ribonuclease A (RNase A) at pH 7.4 and 37 degrees C with ribose, glucose and fructose has been monitored by UV-vis, fluorescence, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and matrix assisted laser desorption ionization spectroscopy-time of flight (MALDI-TOF) methods. The enzymatic activity and DNA binding ability of glycated RNase A was also investigated by an agarose gel-based assay. A precipitation assay examined the ribonucleolytic activity of the glycated enzyme. An increase in incubation time resulted in the formation of high molecular weight AGEs with a decrease in ribonucleolytic activity. Ribose exhibits the highest potency as a glycating agent and showed the greatest reduction in the ribonucleolytic activity of the enzyme. Interestingly, glycated RNase A was unable to bind with the ribonuclease inhibitor (RI) and DNA. The glycated form of the protein was also found to be ineffective in DNA melting unlike native RNase A. PMID- 26365068 TI - Bridging the theory-practice gap. PMID- 26365069 TI - Engaging participants. PMID- 26365070 TI - Is 'Dear colleague' enough? Improving response rates in surveys of healthcare professionals. AB - AIM: To explain a strategy to improve response rates from healthcare professionals to a postal survey in the Republic of Ireland. BACKGROUND: Response rates to surveys conducted among healthcare professionals have been declining steadily. This paper is based on the development of a response rate strategy to address this challenge. DATA SOURCES: A study in Ireland using a survey instrument that relied on the voluntary participation of managers and healthcare professionals. REVIEW METHODS: Database and manual literature searches were undertaken across the literature related to methodology to increase response rates from healthcare professionals. The databases Cinahl, Medline, PsycINFO, Wiley Online Library and Scopus-V.4 were searched using 'response rates' and the terms: 'response rate theory', 'survey response rates', 'increase', 'improve health professionals', 'primary care research', 'health care teams', 'health service research' and 'research participation'. Only English-language publications were reviewed. DISCUSSION: Researchers must be aware of factors that influence healthcare professionals they seek to engage and so they can create research environments that do not preclude or dissuade practitioners from participating. CONCLUSION: The potential impact of poor response rates is a concern for healthcare researchers. Research-based practice is central to improving the quality of health care. Response-rate strategies can enhance research. IMPLICATIONS FOR RESEARCH/PRACTICE: Nurse researchers as part of the broader health research community need to consider potential response rates at the research design stage. Response rate strategies should be developed and outlined as part of their overall research proposal and study reports. PMID- 26365071 TI - Using mixed methods when researching communities. AB - AIM: To argue for the use of mixed methods when researching communities. BACKGROUND: Although research involving minority communities is now advanced, not enough effort has been made to formulate methodological linkages between qualitative and quantitative methods in most studies. For instance, the quantitative approaches used by epidemiologists and others in examining the wellbeing of communities are usually empirical. While the rationale for this is sound, quantitative findings can be expanded with data from in-depth qualitative approaches, such as interviews or observations, which are likely to provide insights into the experiences of people in those communities and their relationships with their wellbeing. DATA SOURCES: Academic databases including The Cochrane Library, MEDLINE, CINAHL, AMED, INTERNURSE, Science Direct, Web of Knowledge and PubMed. REVIEW METHODS: An iterative process of identifying eligible literature was carried out by comprehensively searching electronic databases. DISCUSSION: Using mixed-methods approaches is likely to address any potential drawbacks of individual methods by exploiting the strengths of each at the various stages of research. Combining methods can provide additional ways of looking at a complex problem and improve the understanding of a community's experiences. However, it is important for researchers to use the different methods interactively during their research. CONCLUSION: The use of qualitative and quantitative methods is likely to enrich our understanding of the interrelationship between wellbeing and the experiences of communities. This should help researchers to explore socio-cultural factors and experiences of health and healthcare practice more effectively. PMID- 26365072 TI - Legal, ethical and practical considerations in research involving nurses with dyslexia. AB - AIM: To discuss the legal, ethical and practical considerations in UK studies involving nurses with dyslexia and medication administration errors (MAEs). BACKGROUND: Nurses with dyslexia are a vulnerable population as they are susceptible to misrepresentation in research, especially that which involves a sensitive topic such as MAEs. DISCUSSION: Nurses with dyslexia may be particularly vulnerable to research that could exploit, implicate or attribute unsafe practice to them and their disability. Special consideration should be exercised when researching this population. CONCLUSION: Despite the potential for legal, ethical and practical issues, MAEs and nurses with dyslexia are under researched areas and warrant further research. Benefits can be gained, not only by participants but also those with a vested interest in how best to support dyslexic nurses in clinical practice. IMPLICATIONS FOR RESEARCH/PRACTICE: Through effective design, risks can be identified and minimised, and the research made viable, ethically sound and ultimately beneficial to all those involved. PMID- 26365073 TI - The value of artefacts in stimulated-recall interviews. AB - AIM: To assess the use of artefacts in semi-structured, stimulated-recall interviews in a study exploring mentors' decisions regarding students' competence in practice. BACKGROUND: Few empirical studies have examined how mentors reach a decision when assessing students' performance in practice. Concerns have repeatedly been voiced that students may lack essential skills at the point of registration or that mentors may have failed or been reticent to judge students' performance as unsatisfactory. DATA SOURCES: Student practice assessment documents (PADs) were used in stimulated-recall (SR) interviews with mentors to explore decision making. REVIEW METHODS: A review of the literature identified that artefacts can play a role in triggering a more comprehensive retrospective examination of decision making, thus helping to capture the essence of a mentor's decision over time and in context. DISCUSSION: Use of an artefact to stimulate recall can elicit evidence of thought processes, which may be difficult to obtain in a normal, semi-structured interview. PADs proved to be a valuable way to generate naturalistic decision making. In addition, discussion of artefacts created by participants can promote participant-driven enquiry, thereby reducing researcher bias. CONCLUSION: Identifying an approach that captures post hoc decision making based on sustained engagement and interaction between students and their mentors was a challenge. Artefacts can be used to address the difficulties associated with retrospective introspection about a unique decision. IMPLICATIONS FOR PRACTICE/RESEARCH: There is the potential to increase the use of artefacts in healthcare research. SR can also help novice mentors develop their skills in making decisions regarding assessments of students. PMID- 26365074 TI - The BLEED pilot study: determining the usability of a medical device before the clinical trial. AB - AIM: To discuss the methods of a study which will aim to determine the usability of a medical device not yet approved for use in a clinical trial. BACKGROUND: The Blood Loss Estimation and Evaluation of Drape (BLEED) pilot aims to determine the usability of a drape which measures blood loss during third stage labour. Third stage blood loss is usually estimated visually. This method has been found to be inaccurate. The drape has been tested in developing countries overseas and has been found to more accurately measure third stage blood loss when compared with visual methods. The usability of the drape has not yet been evaluated. REVIEW METHODS: Before starting the BLEED pilot study, the risks to the participants were evaluated and the drape was determined to pose minimal risk of harm for participants. The pilot study will involve recruitment of women and health professionals who will use the drape to measure third stage blood loss and then complete a survey about their opinion of the drape's usability. The data will be used to determine the suitability of using the drape in a clinical trial. DISCUSSION: The benefits of pursing this programme of research outweigh the challenges. The drape has been validated as more accurate than visual estimation for evaluating blood loss during third stage labour, yet the usability has not been established and a clinical trial is needed. This programme of research will determine if routine use of this drape in research and practice is justified. CONCLUSION: This work will assist health professionals who are considering ways to improve clinical outcomes and will particularly inform researchers who are interested in piloting new devices in maternity care. While adherence to monitoring requirements and governance of clinical trials is essential, the system has become complicated for investigator-initiated research using devices. Despite these challenges, the authors of this paper believe that this research programme is justified. IMPLICATIONS FOR PRACTICE: The complexity of navigating documentation and governance required for clinical trials may deter some healthcare professionals who plan to initiate research that involves the use of a medical device. While adherence to monitoring requirements and governance of clinical research is essential, research involving the evaluation of emerging medical technologies can be complicated, particularly for an investigator initiated (clinician) researcher who does not have the support of a biotech company. These issues may deter clinician researchers from initiating trials and impede their ability to implement clinical research. Despite the challenges, the effectiveness and safety of technologies must be evaluated for their effectiveness in improving clinical outcomes for patients. PMID- 26365075 TI - Strategies to enhance recruitment of rural-dwelling older people into community based trials. AB - AIM: To describe strategies that can enhance the recruitment of rural-dwelling older people into clinical trials. BACKGROUND: Recruitment to studies can be time consuming and challenging. Moreover, there are challenges associated with recruiting older people, particularly those living in rural areas. Nevertheless, an adequate sample size is crucial to the validity of randomised controlled trials (RCTs). DATA SOURCES: The authors draw on the literature and their personal experiences, to present a range of flexible and inclusive strategies that have been successfully used to recruit older people into clinical trials. REVIEW METHODS: This paper describes attempts to improve recruitment of rural dwelling, older Thai people to a clinical trial. DISCUSSION: To attract potential participants, researchers should consider minimising the burden of their study and maximising its benefits or convenience for participants. Three factors that may influence participation rates are: personal factors of participants, researchers' personal attributes, and protocol factors. In addition, three important strategies contribute to improving recruitment: understanding the culture of the research setting, identifying the 'gatekeepers' in the setting and building trust with stakeholders. CONCLUSION: Even though the study covered did not recruit a large number of participants, these understandings were crucial and enabled recruitment of a sufficient number of participants in a reasonable timeframe. IMPLICATIONS FOR PRACTICE/RESEARCH: These strategies may be of use in rural settings and with different communities including urban communities. PMID- 26365076 TI - Making a difference through research. PMID- 26365083 TI - Emotional attention capture by facial expressions. AB - Previous studies have shown that emotional facial expressions capture visual attention. However, it has been unclear whether attentional modulation is attributable to their emotional significance or to their visual features. We investigated this issue using a spatial cueing paradigm in which non-predictive cues were peripherally presented before the target was presented in either the same (valid trial) or the opposite (invalid trial) location. The target was an open dot and the cues were photographs of normal emotional facial expressions of anger and happiness, their anti-expressions and neutral expressions. Anti expressions contained the amount of visual changes equivalent to normal emotional expressions compared with neutral expressions, but they were usually perceived as emotionally neutral. The participants were asked to localize the target as soon as possible. After the cueing task, they evaluated their subjective emotional experiences to the cue stimuli. Compared with anti-expressions, the normal emotional expressions decreased and increased the reaction times (RTs) in the valid and invalid trials, respectively. Shorter RTs in the valid trials and longer RTs in the invalid trials were related to higher subjective arousal ratings. These results suggest that emotional facial expressions accelerate attentional engagement and prolong attentional disengagement due to their emotional significance. PMID- 26365084 TI - Li-Filled, B-Substituted Carbon Clathrates. AB - Inside the cages of hypothetical carbon clathrates there is precious little room, even for the smallest atoms, such as Li-unless it is the Li(+) ion that is inserted, in which case a compensating negative charge should be distributed over the carbon cage. The hypothesis explored in this paper is that Li insertion can be achieved with appropriate B substitution within the framework. The resulting structures of 2Li@C10B2 (Clathrate VII), 8Li@C38B8 (Clathrate I), 7Li@C33B7 (Clathrate IV), 6Li@C28B6 (Clathrate H), and 6Li@C28B6 (Clathrate II) are definitely stabilized in theoretical calculations, especially under elevated pressure, as judged by enthalpy criteria and bond length metrics. Different strategies for B substitution (symmetry reduction, following the parent charge distribution, and substitution on the most weakened bonds, relieving stress on bond angles) are explored. Two possible competing channels for Li doping-B substitution, formation of LiBC and C-vacancies, are investigated. PMID- 26365085 TI - "The biggest problem we've ever had to face": how families manage driving cessation with people with dementia. AB - BACKGROUND: It is recognized that people with dementia are likely to need to stop driving at some point following diagnosis. Driving cessation can lead to negative outcomes for people with dementia and their family caregivers (FC), who often experience family conflict and tension throughout the process. Family experiences surrounding driving cessation have begun to be explored but warrant further examination. METHODS: Using a descriptive phenomenological approach, semi structured interviews were undertaken with key stakeholders, including 5 retired drivers with dementia, 12 FC, and 15 health professionals (HP). Data were analyzed inductively to explore the needs and experiences of people with dementia and FC. RESULTS: The data revealed a range of possible interactions between people with dementia and FC. These were organized into a continuum of family dynamics according to levels of collaboration and conflict: in it together, behind the scenes, active negotiations, and at odds. At the in it together end of the continuum, people with dementia and FC demonstrated collaborative approaches and minimal conflict in managing driving cessation. At the at odds end, they experienced open conflict and significant tension in their interactions. Contextual factors influencing family dynamics were identified, along with the need for individualized approaches to support. CONCLUSIONS: The continuum of family dynamics experienced during driving cessation may help clinicians better understand and respond to complex family needs. Interventions should be tailored to families' distinctive needs with consideration of their unique contextual factors influencing dynamics, to provide sensitive and responsive support for families managing driving cessation. PMID- 26365086 TI - Evaluation of a newly developed tobacco cessation program for people with disabilities. AB - BACKGROUND: Tobacco use is the single most preventable cause of morbidity and mortality, accounting for at least 480,000 deaths in the United States annually. People with disabilities smoke at a rate 1.5 times greater than the able-bodied population. Higher incidence of tobacco use among people with disabilities has been directly related to both unique and universal cessation barriers. Despite increased prevalence of tobacco use and cessation obstacles, evidence is lacking on the development of successful interventions targeting people with disabilities. OBJECTIVE: We aimed to assess the feasibility, acceptability, and potential effectiveness of a cessation intervention tailored to people with disabilities. METHODS: Eighteen tobacco users with disabilities (56% African American, 64% male) participated in a 4-week, 8-session tobacco cessation program consisting of group sessions on managing addiction, relapse, and lifestyle changes specific to people with disabilities. Semi-structured interviews were conducted at the conclusion of the program. A follow-up measure of smoking status, triggers, and nicotine replacement therapy usage was completed at 4 weeks and 6 months. RESULTS: Sixteen participants completed the intervention (89%), with participants on average attending 86% of sessions. Most participants rated the program as excellent (83%) or good (8%). Qualitative interviews revealed participants value social support, accessibility, and a tailored program. Four participants (22%) reported abstinence at six months, which is greater than the standard quit rate. CONCLUSION: This study suggests tailoring a cessation program to the characteristics unique to people with disabilities may be critical in delivering meaningful and effective cessation interventions among this population. PMID- 26365088 TI - Robotic-assisted knee arthroplasty. AB - Robotics in total knee arthroplasty (TKA) has undergone vast improvements. Although some of the systems have fallen out of favor due to safety concerns, there has been recent increased interest for semi-active haptic robotic systems that provide intraoperative tactile feedback to the surgeon. The potential advantages include improvements in radiographic outcomes, reducing the incidence of mechanical axis malalignment of the lower extremity and better tissue balance. Proponents of robotic technology believe that these improvements may lead to superior functional outcomes and implant survivorship. We aim to discuss robotic technology development, outcomes of unicompartmental and total knee arthroplasty and the future outlook. Short-term follow-up studies on robotic-assisted knee arthroplasty suggest that, although some alignment objectives may have been achieved, more studies regarding functional outcomes are needed. Furthermore, studies evaluating the projected cost-benefit analyses of this new technology are needed before widespread adoption. Nevertheless, the short-term results warrant further evaluation. PMID- 26365089 TI - Quality of life in osteogenesis imperfecta: A mixed-methods systematic review. AB - Clinical interventions and research have mostly focused on the orthopedic, genetic, and pharmacological outcomes of individuals with osteogenesis imperfecta (OI), and although quality of life (QoL) has gained recognition as an important patient-outcome, it has received little attention in individuals with OI. This mixed-methods systematic review of the literature included five search engines and identified a total of 212 articles. Once study eligibility was reviewed, 10 studies met the inclusion criteria and were included in this mixed-methods review (9 quantitative and 1 qualitative). Among the 10 included QoL studies, six reported on children with OI, three on adults with OI, and one on the parents of children with OI. Physical QoL in children and adults with OI appears to be less than that of the general population, with individuals with more severe OI types reporting worse QoL. On the other hand, mental and psychosocial QoL is the same or better in individuals with OI than that of the general population. Pain, scoliosis activity limitations and participation restrictions due to decreased function are associated with lower levels of physical QoL. Researchers must agree on a definition of QoL as it relates to OI and use validated measures appropriate for evaluating QoL in OI. Pediatric studies should consider both the child and the parent's QOL perceptions as these may differ. QoL in the adult population should not be dismissed in order to offer proper client-centered interventions throughout the lifespan. PMID- 26365087 TI - In vitro and in vivo Evaluation of Synergism between Anti-Tubercular Spectinamides and Non-Classical Tuberculosis Antibiotics. AB - Spectinamides are new semi-synthetic spectinomycin derivatives with potent anti tubercular activity. The reported synergism of the precursor spectinomycin with other antibiotics prompted us to examine whether spectinamides sensitize M. tuberculosis to other antibiotics not traditionally used in the treatment of tuberculosis to potentially expand therapeutic options for MDR/XDR Tuberculosis. Whole cell synergy checkerboard screens were performed using the laboratory strain M. tuberculosis H37Rv, lead spectinamide 1599, and a broad panel of 27 antibiotics. In vitro, 1599 synergized with 11 drugs from 6 antibiotic classes. The observed synergy was tested against clinical isolates confirming synergy with Clarithromycin, Doxycycline and Clindamycin, combinations of which were taken forward for in vivo efficacy determination. Co-administration of 1599 and clarithromycin provided additional bacterial killing in a mouse model of acute tuberculosis infection, but not in a chronic infection model. Further studies indicated that mismatched drug exposure profiles likely permitted induction of phenotypic clarithromycin resistance and subsequent loss of synergism. These studies highlight the importance of validating in vitro synergism and the challenge of matching drug exposures to obtain a synergistic outcome in vivo. Results from this study indicate that a 1599 clarithromycin combination is potentially viable, providing the drug exposures can be carefully monitored. PMID- 26365090 TI - Insight into the molecular dynamics of guest cations confined in deformable azido coordination frameworks. AB - The molecular dynamics of encapsulated cations within perovskite-like coordination polymers [(CH3)3NH][M(N3)3] (M = Mn, Cd) are investigated, which are well controlled by the confined space of a deformable azido framework. The Mn based compound provides a rare example that features an unvaried/varied rotational energy barrier during its two different structural phase transitions. PMID- 26365091 TI - Coordination tuning of cobalt phosphates towards efficient water oxidation catalyst. AB - The development of efficient and stable water oxidation catalysts is necessary for the realization of practically viable water-splitting systems. Although extensive studies have focused on the metal-oxide catalysts, the effect of metal coordination on the catalytic ability remains still elusive. Here we select four cobalt-based phosphate catalysts with various cobalt- and phosphate-group coordination as a platform to better understand the catalytic activity of cobalt based materials. Although they exhibit various catalytic activities and stabilities during water oxidation, Na2CoP2O7 with distorted cobalt tetrahedral geometry shows high activity comparable to that of amorphous cobalt phosphate under neutral conditions, along with high structural stability. First-principles calculations suggest that the surface reorganization by the pyrophosphate ligand induces a highly distorted tetrahedral geometry, where water molecules can favourably bind, resulting in a low overpotential (~0.42 eV). Our findings emphasize the importance of local cobalt coordination in the catalysis and suggest the possible effect of polyanions on the water oxidation chemistry. PMID- 26365092 TI - The association of childhood asthma with mental health and developmental comorbidities in low-income families. AB - OBJECTIVE: The objective of the study was to determine the relationship of childhood asthma with mental health and developmental indicators in low-income families. METHODS: Parents/guardians of approximately 400 children, aged 2-14 years, were recruited from a charity hospital serving low income neighborhoods in the outskirts of Karachi, Pakistan. Mothers of children were interviewed in their local language by a trained nurse. Eight self-reported comorbidities were grouped into two constructs based on factor analysis and conveniently labeled as mental health (anxiety, attention and behavioral problems) and developmental problems (learning, developmental delay, hearing impairment, sleep and speech problems). Data were analyzed using multiple logistic regression, adjusted for age, sex, presence of older siblings, number of people in the household, child birth weight, presence of mold, and family history of asthma or hay fever. RESULTS: Children with asthma had 18 times greater odds of mental health problems (adjusted OR = 18.0, 95% CI: 9.2, 35.1) as compared to children without asthma. The odds of developmental problems were more than 14 times greater for children with asthma (adjusted OR = 14.3, 95% CI: 7.8, 26.1) as compared to children without asthma. CONCLUSIONS: This study found mental and developmental adverse consequences of childhood asthma in low-income families. Identifying and treating asthma at an early age could reduce the burden of comorbidities in this population. PMID- 26365093 TI - Association of asthma with obesity among adolescents exposed to environmental tobacco smoke. AB - OBJECTIVE: The purpose of this study was to examine the association between asthma diagnosis and obesity among adolescents exposed to environmental tobacco smoke (ETS). METHODS: The sample included 28,807 adolescents (13-17 years old) from the National Survey of Children's Health (NSCH) (2011-2012). STUDY DESIGN: The NSCH is a US cross-sectional telephone survey that included at least one child between the ages of 0 and 17 years residing at a household during the time of the interview. Descriptive statistics were used to describe sample characteristics and assess the prevalence of asthma among adolescents with obesity exposed to ETS. Logistic regression models were built to assess the effect of obesity on asthma diagnosis within the context of ETS exposure. RESULTS: The prevalence of asthma among adolescents was 10.4% and the obesity was 13.2%. Adolescents with obesity exposed to ETS within the home were significantly (p < 0.05) more likely to have an asthma diagnosis (23%) compared with non-obese (10.9%) residing in similar households. Adjusted odds ratios showed that adolescents with obesity were 2.07 (95% CI, 1.15, 3.70) times more likely to have asthma if they were exposed to ETS inside their homes. CONCLUSION: The findings indicate that adolescents with obesity are more likely to be diagnosed with asthma if they are exposed to ETS in the household. It is important that the association between obesity and asthma is examined within the context of environmental risk factors in future studies, as this may shed some light to underlying mechanisms between these two serious public health issues. PMID- 26365094 TI - Correction to Synthesis of Pyrazines from Rhodium-Catalyzed Reaction of 2H Azirines with N-Sulfonyl 1,2,3-Triazoles. PMID- 26365095 TI - The prokaryotic zinc-finger: structure, function and comparison with the eukaryotic counterpart. AB - Classical zinc finger (ZF) domains were thought to be confined to the eukaryotic kingdom until the transcriptional regulator Ros protein was identified in Agrobacterium tumefaciens. The Ros Cys2 His2 ZF binds DNA in a peculiar mode and folds in a domain significantly larger than its eukaryotic counterpart consisting of 58 amino acids (the 9-66 region) arranged in a betabetabetaalphaalpha topology, and stabilized by a conserved, extensive, 15-residue hydrophobic core. The prokaryotic ZF domain, then, shows some intriguing new features that make it interestingly different from its eukaryotic counterpart. This review will focus on the prokaryotic ZFs, summarizing and discussing differences and analogies with the eukaryotic domains and providing important insights into their structure/function relationships. PMID- 26365096 TI - Teriflunomide: a once-daily oral medication for the treatment of relapsing forms of multiple sclerosis. AB - PURPOSE: The purpose was to summarize US prescribing information for teriflunomide in the treatment of patients with relapsing forms of multiple sclerosis (RMS), with reference to clinical efficacy and safety outcomes. METHODS: In September 2012, the US Food and Drug Administration granted approval for the use of teriflunomide, 14 mg and 7 mg once daily, to treat RMS on the basis of the results of a Phase II study and the Phase III TEMSO (Teriflunomide Multiple Sclerosis Oral) trial. After recent updates to the prescribing information (October 2014), key findings from these and 2 other Phase III clinical trials, TOWER (Teriflunomide Oral in People With Relapsing Multiple Sclerosis) and TOPIC (Oral Teriflunomide for Patients with a First Clinical Episode Suggestive of Multiple Sclerosis), and practical considerations for physicians are summarized. FINDINGS: Teriflunomide, 14 mg and 7 mg, significantly reduced mean number of unique active lesions on magnetic resonance imaging (MRI; P < 0.05 for both doses) in the Phase II study. In the TEMSO and TOWER studies, the 14-mg dose of teriflunomide significantly reduced annualized relapse rate (31% and 36% relative risk reduction compared with placebo, respectively; both P < 0.001) and risk of disability progression sustained for 12 weeks (hazard ratio vs placebo 0.70 and 0.69, respectively; both P < 0.05). The 7-mg dose significantly (P < 0.02) reduced annualized relapse rate in both studies, although the reduction in risk of disability progression was not statistically significant. Teriflunomide treatment was also associated with significant efficacy on MRI measures of disease activity in TEMSO; both doses significantly reduced total lesion volume and number of gadolinium-enhancing T1 lesions. TOPIC evaluated patients with a first clinical event consistent with acute demyelination and brain MRI lesions characteristic of multiple sclerosis. More patients were free of relapse in the teriflunomide 14-mg and 7-mg groups than in the placebo group (P < 0.05 for both comparisons). In safety data pooled from the 4 studies, adverse events occurring in >=2% of patients and >=2% higher than in the placebo group were headache, alanine aminotransferase increase, diarrhea, alopecia (hair thinning), nausea, paresthesia, arthralgia, neutropenia, and hypertension. Routine monitoring procedures before and on treatment are recommended to assess potential safety issues. Women of childbearing potential must use effective contraception and, in the event of pregnancy, undergo an accelerated elimination procedure to reduce plasma concentrations of teriflunomide. IMPLICATIONS: Clinical evidence suggests that teriflunomide is an effective therapeutic choice for patients with RMS, both as an initial treatment and as an alternative for patients who may have experienced intolerance or inadequate response to a previous or current disease-modifying therapy. PMID- 26365097 TI - Cognitive Emotion Regulation as a Mediator between Posttraumatic Stress Symptoms and Hypomanic Personality within a Non-Clinical Population. AB - BACKGROUND: There is a high prevalence of traumatic life events within individuals diagnosed with bipolar disorder. However, currently there is limited theoretical understanding of this relationship. AIMS: To explore whether non clinical symptoms of posttraumatic stress have a direct effect on the non clinical symptoms of bipolar disorder, or whether this relationship is mediated by cognitive emotion regulation strategies. METHOD: A cross-sectional design within non-clinical participants completing an online survey including the Impact of Events Scale, Cognitive Emotion Regulation Questionnaire and the Hypomanic Personality Scale. RESULTS: Posttraumatic stress symptoms were associated with hypomanic personality. Intrusive memories contributed a small but significant proportion of the variance between these two measures. Rumination of negative emotions mediated the relationship between posttraumatic stress and hypomanic personality. CONCLUSIONS: The relationship between traumatic events and an increased prevalence of bipolar disorder remains poorly understood. Further research should explore rumination as a potential target for treatment within those suffering from both posttraumatic stress and bipolar disorder. PMID- 26365098 TI - A continuum state variable theory to model the size-dependent surface energy of nanostructures. AB - We propose a continuum-based state variable theory to quantify the excess surface free energy density throughout a nanostructure. The size-dependent effect exhibited by nanoplates and spherical nanoparticles i.e. the reduction of surface energy with reducing nanostructure size is well-captured by our continuum state variable theory. Our constitutive theory is also able to predict the reducing energetic difference between the surface and interior (bulk) portions of a nanostructure with decreasing nanostructure size. PMID- 26365099 TI - Photodecomposition, photomutagenicity and photocytotoxicity of retinyl palmitate under He-Ne laser photoirradiation and its effects on photodynamic therapy of cancer cells in vitro. AB - OBJECTIVE: Our aim was to study photodecomposition, photomutagenicity and cytotoxicity of retinyl palmitate (RP), a principal storage form of vitamin A in humans and animals, under He-Ne laser photoirradiation. Moreover, the effect of different concentrations and timing protocol of antioxidants on photodynamic therapy (PDT) is contradictory, so the effect of RP (as antioxidant) on the PDT cytotoxicity was studied. METHODS: Photomutagenicity was tested by Ames test. Photodecomposition was studied by UV-vis spectroscopy. Cytotoxicity was measured with MTT-assay. Moreover, the effect of PDT, using hematoporphyrin derivatives (HpD) as photosensitizer under He-Ne laser irradiation (10 J/cm(2)), was studied on HeLa cells either with or without RP (1-100 MUM) which incubated with the cells for short or long incubation period (1 h or 24 h) prior to PDT. RESULTS: No photodecomposition of RP alone was obseved whereas there is a little photodecomposition of RP only in presence of HpD under irradiation with He-Ne laser. Moreover, no photomutagenicity was observed in Salmonella typhimurium strains under laser irradiation in presence or absence of HpD. RP alone (1-100 MUM) significantly decrease the viability of HeLa cells. Laser irradiation of HeLa cells pre-incubated with RP alone for 24 h showed further significant decrease in viability of the cells. While RP incubations for 1 h before PDT had slight effect on the cells, 24 h incubation before PDT enhanced the cytotoxicity of PDT on HeLa cells. CONCLUSIONS: RP can be used 24 h before PDT to enhance its effects. RP is not mutagenic under irradiation with He-Ne laser. PMID- 26365100 TI - Conjugation Approach To Produce a Staphylococcus aureus Synbody with Activity in Serum. AB - Synbodies show promise as a new class of synthetic antibiotics. Here, we explore improvements in their activity and production through conjugation chemistry. Maleimide conjugation is a widely used conjugation strategy due to its high yield, selectivity, and low cost. We used this strategy to conjugate two antibacterial peptides to produce a bivalent antibacterial peptide, called a synbody that has bactericidal activity against methicillin resistant Staphylococcus aureus (MRSA). The synbody was prepared by conjugation of a partially d-amino acid substituted synthetic antibacterial peptide to a bis maleimide scaffold. The synbody slowly degrades in serum, but also undergoes exchange reactions with other serum proteins, such as albumin. Therefore, we hydrolyzed the thiosuccinimide ring using a mild hydrolysis protocol to produce a new synbody with similar bactericidal activity. The synbody was now resistant to exchange reactions and maintained bactericidal activity in serum for 2 h. This work demonstrates that low-cost maleimide coupling can be used to produce antibacterial peptide conjugates with activity in serum. PMID- 26365101 TI - Health behaviors and personality in burnout: a third dimension. AB - The high prevalence of burnout among healthcare professionals warrants a thorough examination aimed at improving the current understanding of its predictors and preventive measures. Cecil et al. have underscored the alarming prevalence of burnout among medical students and assessed its association with demographic, lifestyle, and behavioral factors. Of interest, health behaviors were found to be predictive of burnout. The study suggests certain behaviors (such as high physical activity) to be protective, and thus, calls for their establishment early in college life to prevent the development of this professionally-disabling mental state. Although the adoption of advisable health behaviors may independently reduce the risk of burnout, recognition of the existence and influence of closely related factors allows for an enhanced understanding and a greater precision for any conclusions to be made. Personality, through deductive and inductive reasoning, is likely to exert significant influence on both the student's behavior and his/her susceptibility to burnout. Thus, with personality representing--in and of itself--a principal model for prediction of burnout risk, controlling for personality traits when addressing health behaviors' influence per se on burnout is essential. PMID- 26365103 TI - Graphonomics and its contribution to the field of motor behavior: A position statement. AB - The term graphonomics was conceived in the early 1980s; it defined a multidisciplinary emerging field focused on handwriting and drawing movements. Researchers in the field of graphonomics have made important contribution to the field of motor behavior by developing models aimed to conceptualize the production of fine motor movements using graphical tools. Although skeptics have argued that recent technological advancements would reduce the impact of graphonomic research, a shift of focus within in the field of graphonomics into fine motor tasks in general proves the resilience of the field. Moreover, it has been suggested that the use of fine motor movements due to technological advances has increased in importance in everyday life. It is concluded that the International Graphonomics Society can have a leading role in fostering collaborative multidisciplinary efforts and can help with the dissemination of findings contributing to the field of human movement sciences to a larger public. PMID- 26365104 TI - Localized pemphigus vulgaris clinically masquerading as lichen planus and actinic keratosis. PMID- 26365105 TI - Screening of subclinical hypothyroidism during gestational diabetes in Pakistani population. AB - OBJECTIVE: The increased prevalence of adverse effects of altered thyroid functions in pregnancy inspired us to study the frequency of subclinical hypothyroidism (SCH) and the relationship with glycaemic control and foetal weight in pregnant females with and without gestational diabetes mellitus (GDM) in Pakistani population. PATIENTS AND METHODS: Five hundred and eight pregnant females were enrolled and grouped as per the International Diabetes Association criteria into GDM (n = 208) and healthy control (n = 300). Random blood glucose (RBG), thyroid function tests, anthropometric analysis and foetal ultra sound scans were performed on all study subjects. Data were analysed using Mann-Whitney U test and Chi-square test wherever applicable. Spearman correlation and multiple regression analysis were performed. p values of <0.05 was considered significant. RESULTS: A total of 61.5% GDM subjects depicted SCH with normal circulating T4 and T3 versus 6.0% healthy controls (p-value < 0.001). Moreover, TSH remained independently associated with RBG (r = 0.109; p < 0.05), poor glycaemic control (r = 0.227; p < 0.001) and negatively associated with foetal growth (r = -0.206; p < 0.001). CONCLUSION: The detection of high TSH with normal T3 and T4 in females with GDM strongly emphasises the need of thyroid screening as a routine in all antenatal clinics. PMID- 26365106 TI - Self-other integration and distinction in schizophrenia: A theoretical analysis and a review of the evidence. AB - Difficulties in self-other processing lie at the core of schizophrenia and pose a problem for patients' daily social functioning. In the present selective review, we provide a framework for understanding self-other integration and distinction, and impairments herein in schizophrenia. For this purpose, we discuss classic motor prediction models in relation to mirror neuron functioning, theory of mind, mimicry, self-awareness, and self-agency phenomena. Importantly, we also discuss the role of more recent cognitive expectation models in these phenomena, and argue that these cognitive models form an essential contribution to our understanding of self-other integration and distinction. In doing so, we bring together different lines of research and connect findings from social psychology, affective neuropsychology, and psychiatry to further our understanding of when and how people integrate versus distinguish self and other, and how this goes wrong in schizophrenia patients. PMID- 26365102 TI - Does low-energy sweetener consumption affect energy intake and body weight? A systematic review, including meta-analyses, of the evidence from human and animal studies. AB - By reducing energy density, low-energy sweeteners (LES) might be expected to reduce energy intake (EI) and body weight (BW). To assess the totality of the evidence testing the null hypothesis that LES exposure (versus sugars or unsweetened alternatives) has no effect on EI or BW, we conducted a systematic review of relevant studies in animals and humans consuming LES with ad libitum access to food energy. In 62 of 90 animal studies exposure to LES did not affect or decreased BW. Of 28 reporting increased BW, 19 compared LES with glucose exposure using a specific 'learning' paradigm. Twelve prospective cohort studies in humans reported inconsistent associations between LES use and body mass index (-0.002 kg m(-)(2) per year, 95% confidence interval (CI) -0.009 to 0.005). Meta analysis of short-term randomized controlled trials (129 comparisons) showed reduced total EI for LES versus sugar-sweetened food or beverage consumption before an ad libitum meal (-94 kcal, 95% CI -122 to -66), with no difference versus water (-2 kcal, 95% CI -30 to 26). This was consistent with EI results from sustained intervention randomized controlled trials (10 comparisons). Meta analysis of sustained intervention randomized controlled trials (4 weeks to 40 months) showed that consumption of LES versus sugar led to relatively reduced BW (nine comparisons; -1.35 kg, 95% CI -2.28 to -0.42), and a similar relative reduction in BW versus water (three comparisons; -1.24 kg, 95% CI -2.22 to 0.26). Most animal studies did not mimic LES consumption by humans, and reverse causation may influence the results of prospective cohort studies. The preponderance of evidence from all human randomized controlled trials indicates that LES do not increase EI or BW, whether compared with caloric or non-caloric (for example, water) control conditions. Overall, the balance of evidence indicates that use of LES in place of sugar, in children and adults, leads to reduced EI and BW, and possibly also when compared with water. PMID- 26365107 TI - Cognition in at-risk mental states for psychosis. AB - RATIONALE: The devastating nature of schizophrenia and treatment limitations have triggered a search for early detection methods to enable interventions to be implemented as soon as the first signs and symptoms appear. In this effort, several studies have investigated the cognitive functions in individuals regarded as being in at-risk mental states (ARMS) for psychosis. OBJECTIVE: Our aim was to make a systematic review of the literature regarding basic and social cognition in individuals in ARMS following the guidelines of the PRISMA statement. RESULTS: In general, the results of the 49 articles included in the review show that individuals in ARMS have pervasive cognitive deficits that seem to be greater in individuals who later convert to psychosis. CONCLUSIONS: Cognitive impairment can be detected in individuals considered to be in ARMS according to current classifications and may serve as a risk marker for psychotic conversion; however, the lack of standardized criteria to define ARMS and of homogeneous cognitive assessment methods hamper the generalization of findings from different studies. PMID- 26365108 TI - Mental number space in three dimensions. AB - A large number of experimental findings from neuroscience and experimental psychology demonstrated interactions between spatial cognition and numerical cognition. In particular, many researchers posited a horizontal mental number line, where small numbers are thought of as being to the left of larger numbers. This review synthesizes work on the mental association between space and number, indicating the existence of multiple spatial mappings: recent research has found associations between number and vertical space, as well as associations between number and near/far space. We discuss number space in three dimensions with an eye on potential origins of the different number mappings, and how these number mappings fit in with our current knowledge of brain organization and brain culture interactions. We derive novel predictions and show how this research fits into a general view of cognition as embodied, grounded and situated. PMID- 26365109 TI - Median Arcuate Ligament Syndrome Is Not a Vascular Disease. AB - BACKGROUND: Median arcuate ligament syndrome (MALS) is a rare disorder characterized by postprandial abdominal pain, weight loss, and celiac stenosis. Diagnosis can be challenging, leading to a delay in treatment. We report on our continued experience using a laparoscopic approach for this uncommon diagnosis. METHODS: This is an Institutional Review Board-approved, prospectively collected retrospective analysis of patients treated with laparoscopic MAL release at our institution. Data collected included patient demographics, preoperative symptoms, operative approach, and postoperative outcomes. Patients were then contacted to complete a postoperative survey designed to assess the improvement of symptoms and overall patient satisfaction. RESULTS: A total of 39 patients (33 women and 6 men) underwent laparoscopic MAL release from March 2007 to July 2014. Mean age was 40.6 years (range, 17-77 years). Thirty of 39 patients had a postoperative celiac axis ultrasound. Twenty-three had a patent celiac axis on postoperative duplex. Of the remaining 7, 5 with residual celiac axis stenosis and 1 with occlusion, reported complete resolution of their symptoms. One remaining patient with occlusion remained symptomatic. Thirty-three of 39 (84.6%) reported symptom relief after surgery. Nine of 33 (27.3%) responders had cardiovascular risk factors versus 4 of 6 (67%) nonresponders. Five patients with atypical presentations underwent preoperative diagnostic celiac plexus block using local anesthetic, with 4 reporting symptom reliefs after block. These 4 patients also reported postoperative symptom relief. One patient of 39 received a postoperative celiac stent placement and remained symptomatic. There were 4 conversions to open surgery (10.3%) and no deaths. CONCLUSIONS: Laparoscopic MAL release continues to be a safe and effective means of managing MALS. Our data suggest that the symptoms associated with MALS are not related to vascular compromise, and atherosclerotic risk factors may predict poorer outcomes. Symptomatic relief is seen in the vast majority of patients undergoing this procedure. However, patient selection remains critically important in obtaining optimal results. PMID- 26365110 TI - Tips About the Cordis INCRAFT Endograft. AB - BACKGROUND: Recently, the new Cordis INCRAFT abdominal aortic aneurysm (AAA) Stent-Graft System ultra low-profile device has been introduced in the clinical practice of endovascular aortic repair (EVAR) for the treatment of infrarenal AAAs (iAAAs). In our operative unit, it has been used since November 2014. We report our initial experience with the use of this novel device. We further discuss some technical aspects about the use of the endograft. METHODS: Data of all patients undergoing elective EVAR in our Division of Vascular Surgery using the Cordis INCRAFT AAA Stent-Graft System from November 2014 till now were retrospectively collected in a database and outcomes reviewed. Follow-up data were analyzed to evaluate primary success, survival, complications, and device related events. Statistical analysis was performed using JMP((r)) 5.1.2 (SAS Institute Inc., Cary, NC). Continuous variables are reported as mean +/- standard deviation, and categorical variables are presented as n (%). RESULTS: From November 2014 till now in our institution, a total of 10 patients (7 male; mean age, 76.3 years old; range, 65-87 years) underwent elective exclusion of an iAAA with a challenge iliac anatomy (minimum access vessel, 6.7 mm) using Cordis INCRAFT endoprosthesis. There were 9 AAA and a left common iliac artery aneurysm 50 mm in diameter, involving the internal iliac artery. Primary success was achieved in 90% as 1 patient presented an immediate type Ia endoleak which was resolved by the placement of a proximal aortic cuff. There was 1 intraoperative acute leg ischemia requiring a left popliteal Fogarty thrombectomy. Three patients (30%) presented a postimplantation syndrome. No other complications occurred neither during in-hospital stay (mean, 3.4 days; range, 2-4 days) nor during follow-up. CONCLUSIONS: In our experience, the Cordis INCRAFT AAA System was a safe and effective device. Our reflections about technical aspects of the use of this device will probably find their answer when further studies will report shared experiences and results about using this type of endograft. PMID- 26365111 TI - Late Longitudinal Comparison of Endovascular and Open Popliteal Aneurysm Repairs. AB - BACKGROUND: We sought to define suitable anatomy predicting durable exclusion of popliteal artery aneurysms (PAAs) and define optimal patient selection criteria for endovascular repair (ER). METHODS: Seventy-five PAAs were repaired in 66 patients (64 male and 2 female) over the past 13 years. Fifty-two aneurysms (69%) were treated with open surgical exclusion and/or bypass using autologous vein (69%) or polytetrafluorethylene (31%) conduit. Extended bypass targets required inflow from the common femoral artery in 15% of limbs and outflow via a tibial artery in 31%. Since May 2001, ER was considered in patients with high medical risk, limited vessel tortuosity, absence of significant occlusive disease (ankle brachial index > 0.9), and PAA not involving below knee segments. Interventions were performed via antegrade femoral access in 23 limbs (31%) using commercially available endografts. Device diameters ranged between 7 and 13 mm, with a median of 2 devices per PAA, and mean treatment length was 22 cm (range, 5-36 cm). All patients were followed with duplex ultrasound surveillance and were prescribed clopidogrel and/or aspirin. RESULTS: Patients treated endovascularly were older (82 vs. 70 years old, P = 0.01), but had shorter length of stay (2 vs. 12 days, P = 0.01) and lower complication rates (8% vs. 17%, P = 0.02). Mean surveillance interval was 39 months with similar 4-year survival (67.9% open and 73.7% endovascular). Primary and secondary patencies were 67.2%, 67.2% after ER and 65.5%, 78.4% for open at 4 years, respectively. Four of 6 endovascular failures were thrombosis within 4 months of intervention and had conversions to open repair (OR). Secondary interventions were required after 48.1% of endovascular and 54.1% of ORs. Three limbs were lost in the series (2 open and 1 endovascular). CONCLUSIONS: Similar outcomes can be expected after endovascular and open PAA repair with adherence to specific anatomic and technical selection requisites. PMID- 26365112 TI - Diastereoselective construction of anti-4,5-disubstituted-1,3-dioxolanes via a bismuth-mediated two-component hemiacetal oxa-conjugate addition of gamma-hydroxy alpha,beta-unsaturated ketones with paraformaldehyde. AB - The bismuth-mediated two-component hemiacetal oxa-conjugate addition of gamma hydroxy-alpha,beta-unsaturated ketones with paraformaldehyde affords anti-4,5 disubstituted-1,3-dioxolanes in an efficient and stereoselective manner. The reaction provides a practical, inexpensive and atom-economical approach to these types of heterocycles, which represent useful intermediates for target-directed synthesis and precursors to syn-1,2-diols. PMID- 26365113 TI - Coping with problematic drug use in the family: An evaluation of the Stepping Stones program. AB - INTRODUCTION AND AIMS: Problematic substance use by an individual is often highly destructive to their family, creating emotional turmoil and destroying healthy family functioning. The aim of this study was to evaluate the impact of participation in the Stepping Stones family support program on the coping capacity of family members affected by another's substance use. DESIGN AND METHODS: A pre and post study of the Stepping Stones intervention for families was conducted, involving 108 participants recruited from March 2013 to March 2014. RESULTS: Significant improvement in coping across all domains was observed post course and at follow up on both outcome measures (Coping Questionnaire and the Family Drug Support Questionnaire). Improvements for participants were either increased or sustained at 3 months follow up. Participants recorded high satisfaction ratings. DISCUSSION AND CONCLUSIONS: The findings from this study demonstrate that participation in the Stepping Stones program assists family members to cope better with problematic substance use of a family member, as indicated by reductions in negative coping strategies, such as over-engagement, making excuses for the drug user or hopelessly tolerating the problem, and improvements in positive coping strategies such as self-care and engagement with their own activities and interests. [Gethin A, Trimingham T, Chang T, Farrell M, Ross J. Coping with problematic drug use in the family: An evaluation of the Stepping Stones program. Drug Alcohol Rev 2016;35:470-476]. PMID- 26365114 TI - Moment to moment variability in functional brain networks during cognitive activity in EEG data. AB - Functional brain networks (FBNs) are gaining increasing attention in computational neuroscience due to their ability to reveal dynamic interdependencies between brain regions. The dynamics of such networks during cognitive activity between stimulus and response using multi-channel electroencephalogram (EEG), recorded from 16 healthy human participants are explored in this research. Successive EEG segments of 500[Formula: see text]ms duration starting from the onset of cognitive stimulation have been used to analyze and understand the cognitive dynamics. The approach employs a combination of signal processing techniques, nonlinear statistical measures and graph theoretical analysis. The efficacy of this approach in detecting and tracking cognitive load induced changes in EEG data is clearly demonstrated using graph metrics. It is revealed that most cognitive activity occurs within approximately 500[Formula: see text]ms of the stimulus presentation in addition to temporal variability in the FBNs. It is shown that mutual information (MI), a nonlinear measure, produces good correlations between the EEG channels thus enabling the construction of FBNs which are sensitive to cognitive load induced changes in EEG. Analyses of the dynamics of FBNs and the visualization approach reveal hard to detect subtle changes in cognitive function and hence may lead to a better understanding of cognitive processing in the brain. The techniques exploited have the potential to detect human cognitive dysfunction (impairments). PMID- 26365115 TI - Challenges faced in the clinical application of artificial anal sphincters. AB - Fecal incontinence is an unresolved problem, which has a serious effect on patients, both physically and psychologically. For patients with severe symptoms, treatment with an artificial anal sphincter could be a potential option to restore continence. Currently, the Acticon Neosphincter is the only device certified by the US Food and Drug Administration. In this paper, the clinical safety and efficacy of the Acticon Neosphincter are evaluated and discussed. Furthermore, some other key studies on artificial anal sphincters are presented and summarized. In particular, this paper highlights that the crucial problem in this technology is to maintain long-term biomechanical compatibility between implants and surrounding tissues. Compatibility is affected by changes in both the morphology and mechanical properties of the tissues surrounding the implants. A new approach for enhancing the long-term biomechanical compatibility of implantable artificial sphincters is proposed based on the use of smart materials. PMID- 26365116 TI - Immunotherapy of DC-CIK cells enhances the efficacy of chemotherapy for solid cancer: a meta-analysis of randomized controlled trials in Chinese patients. AB - OBJECTIVE: Professional antigen-presenting dendritic cells (DCs) and cytokine induced killer (CIK) cells, components of anti-cancer therapy, have shown clinical benefits and potential to overcome chemotherapeutic resistance. To evaluate whether DC-CIK cell-based therapy improves the clinical efficacy of chemotherapy, we reviewed the literature on DC-CIK cells and meta-analyzed randomized controlled trials (RCTs). METHODS: We searched several databases and selected studies using predefined criteria. RCTs that applied chemotherapy with and without DC-CIK cells separately in two groups were included. Odds ratio (OR) and mean difference (MD) were reported to measure the pooled effect. RESULTS: Twelve reported RCTs (826 patients), which were all performed on Chinese patients, were included. Combination therapy exhibited better data than chemotherapy: 1-year overall survival (OS) (OR=0.22, P<0.01), 2-year OS (OR=0.28, P<0.01), 3-year OS (OR=0.41, P<0.01), 1-year disease-free survival (DFS) (OR=0.16, P<0.05), 3-year DFS (OR=0.32, P<0.01), objective response rate (ORR) (OR=0.54, P<0.01), and disease control rate (DCR) (OR=0.46, P<0.01). Moreover, the levels of CD3(+) T-lymphocytes (MD=-11.65, P<0.05) and CD4(+) T-lymphocytes (MD=-8.18, P<0.01) of the combination group were higher. CONCLUSIONS: Immunotherapy of DC-CIK cells may enhance the efficacy of chemotherapy on solid cancer and induces no specific side effect. Further RCTs with no publishing bias should be designed to confirm the immunotherapeutic effects of DC-CIK cells. PMID- 26365117 TI - DNA methylation level of promoter region of activating transcription factor 5 in glioma. AB - Transcription factors, which represent an important class of proteins that play key roles in controlling cellular proliferation and cell cycle modulation, are attractive targets for cancer therapy. Previous researches have shown that the expression level of activating transcription factor 5 (ATF5) was frequently increased in glioma and its acetylation level was related to glioma. The purposes of this study were to explore the methylation level of ATF5 in clinical glioma tissues and to explore the effect of ATF5 methylation on the expression of ATF5 in glioma. Methylation of the promoter region of ATF5 was assayed by bisulfite specific polymerase chain reaction (PCR) sequencing analysis in 35 cases of glioma and 5 normal tissues. Quantitative real-time PCR (qRT-PCR) was also performed to detect ATF5 mRNA expression in 35 cases of glioma and 5 normal tissues. Clinical data were collected from the patients and analyzed. The percentages of methylation of the ATF5 gene in the promoter region in healthy control, patients with well-differentiated glioma, and those with poorly differentiated glioma were 87.78%, 73.89%, and 47.70%, respectively. Analysis of the methylation status of the promoter region of the ATF5 gene showed a gradually decreased methylation level in poorly differentiated glioma, well-differentiated glioma, and normal tissues (P<0.05). There was also a significant difference between well-differentiated glioma and poorly differentiated glioma (P<0.05). ATF5 mRNA expression in glioma was significantly higher than that in the normal tissues (P<0.05). This study provides the first evidence that the methylation level of ATF5 decreased, and its mRNA expression was evidently up-regulated in glioma. PMID- 26365118 TI - Decreased PSD95 expression in medial prefrontal cortex (mPFC) was associated with cognitive impairment induced by sevoflurane anesthesia. AB - OBJECTIVE: Though sevoflurane has been widely used as an anesthetic in surgery, recent studies have shown that exposure to sevoflurane alone could lead to postoperative cognitive dysfunction (POCD), of which the mechanisms still remain largely unknown. The medial prefrontal cortex (mPFC) is known to be implicated in various cognitive impairments, including working memory and attentional processes. In the present study, we tried to identify dysregulated gene expression in mPFC and investigate the underlying mechanisms involved in POCD. METHODS: Behavioral tests, including elevated plus-maze, O-maze, and Y-maze tests, were performed on Wistar rats exposed to sevoflurane. Whole-genome mRNA profiling of mPFC from Wistar rats after exposure to sevoflurane was carried out. Real-time polymerase chain reaction (PCR) was done to verify the differentially expressed genes. RESULTS: Significant impairment of working memory of rats after exposure to sevoflurane was observed. A total of 119 of 7319 detected mRNAs showed significantly different expression between rats with and without sevoflurane exposure (fold change (FC)>2.0, P<0.05, and false discovery rate (FDR)<0.05), among which 74 mRNAs were down-regulated and 45 mRNAs were up regulated. Postsynaptic density-95 (PSD95, also named DLG4) showed the most significantly decreased expression in mPFC and further investigation indicated that PSD95 expression level was correlated with spatial working memory performance. CONCLUSIONS: Our study revealed that PSD95 might be involved in the mechanism of POCD, which could provide clues for preventing POCD in clinical operations. PMID- 26365119 TI - Mycophenolate mofetil plus prednisone for inducing remission of Henoch-Schonlein purpura nephritis: a retrospective study. AB - OBJECTIVE: The treatment of Henoch-Schonlein purpura (HSP) with moderate proteinuria remains controversial. We retrospectively analyzed the efficacy of immune suppressants, with a particular emphasis on mycophenolate mofetil (MMF). METHODS: Ninety-five HSP patients with moderate proteinuria (1.0-3.5 g/24 h) after at least three months of therapy with angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) were divided into three groups: an MMF group (n=33) that received MMF 1.0-1.5 g/d combined with prednisone (0.4-0.5 mg/(kg.d)), a corticosteroid (CS) group (n=31) that received full-dose prednisone (0.8-1.0 mg/(kg.d)), and a control group (n=31). Patients in the MMF and CS groups continued to take ACEI or ARB at the original dose. The patients in the control group continued to take ACEI or ARB but the dose was increased by (1.73+/-0.58)-fold. The patients were followed up for 6-78 months (median 28 months). RESULTS: The baseline proteinuria was higher in the MMF group ((2.1+/-0.9) g/24 h) than in the control group ((1.6+/-0.8) g/24 h) (P=0.039). The proteinuria decreased significantly in all groups during follow-up, but only in the MMF group did it decrease significantly after the first month. At the end of follow-up, the proteinuria was (0.4+/-0.7) g/24 h in the MMF group and (0.4+/ 0.4) g/24 h in the CS group, significantly lower than that in the control group ((0.9+/-1.1) g/24 h). The remission rates in the MMF group, CS group, and control group were respectively 72.7%, 71.0%, and 48.4% at six months and 72.7%, 64.5%, and 45.2% at the end of follow-up. The overall number of reported adverse events was 17 in the MMF group, 30 in the CS group, and 6 in the control group (P<0.001). CONCLUSIONS: MMF with low-dose prednisone may be as effective as full dose prednisone and tend to have fewer adverse events. Therefore, it is probably superior to conservative treatments of adult HSP patients with moderate proteinuria. PMID- 26365120 TI - Protective effect of L-carnitine in cyclophosphamide-induced germ cell apoptosis. AB - Cyclophosphamide (CP) is a widely used anti-cancer agent; however, it can also induce serious male infertility. There are currently no effective drugs to alleviate this side-effect. L-Carnitine has been used to treat male infertility, but whether it can be used to protect against CP-induced male infertility is still unclear. This study aims to explore the effect and mechanism of L-carnitine in male infertility induced by CP. CP was used to establish an animal model. After three weeks of treatment, rats were sacrificed and testis and serum were harvested for further evaluation. Testosterone and estrogen levels were measured by enzyme-linked immunosorbent assay (ELISA). Testicular injury was examined by hematoxylin and eosin (H & E) staining, and germ-cell apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). The expression of LC3 and Beclin-1 was examined by immunohistochemistry, Western blot, and real-time polymerase chain reaction (PCR), respectively. Compared with the CP group, L-carnitine significantly increases sperm motility, viability, and testosterone level (P<0.05). Western blot and real-time PCR results showed that L carnitine treatment can significantly up-regulate the LC3-II and Beclin-1 expression in the CP+L-carnitine group when compared with the control group (P<0.05). In addition, TUNEL-positive cells were also more numerous in the CP group; however, L-carnitine can effectively retard cell apoptosis in the CP+L carnitine group. In conclusion, L-carnitine contributes to the inhibition of cell apoptosis and the modulation of autophagy in protecting CP-induced testicular injury. These results suggest the applicability of L-carnitine in the treatment of male infertility. PMID- 26365121 TI - Low-grade risk of hypercoagulable state in patients suffering from diabetes mellitus type 2. AB - OBJECTIVE: Diabetes, including type 1 and type 2, is associated with the hypercoagulable state. The aim of this study is to evaluate the concentration of selected hemostatic parameters and vascular endothelial growth factor-A (VEGF-A) in diabetic subjects. METHODS: The study was conducted in 62 patients with diabetes. Group I consisted of 27 patients having uncontrolled diabetes with microalbuminuria and Group II included 35 well-controlled diabetic patients. The control group was made up of 25 healthy volunteers. In the citrate plasma, the concentrations of tissue factor (TF), tissue factor pathway inhibitor (TFPI), thrombin-antithrombin (TAT) complexes, and D-dimer were assayed. Serum concentrations of VEGF-A, lipid profile, creatinine, and plasma fasting glucose were measured and in the versene plasma the concentration of HbA1c was determined. RESULTS: In the patients with uncontrolled diabetes, higher concentrations of TF, TFPI, and VEGF-A were observed, as compared with the well controlled diabetics group and the control group. A significantly lower activity of antiplasmin was reported in patients from Group I as compared with the control group. In Group I, using the multivariate regression analysis, the glomerular filtration rate was independently associated with VEGF-A and dependently associated with total cholesterol. CONCLUSIONS: The study showed higher concentrations of TF and TFPI in the patients with uncontrolled diabetes with microalbuminuria, which is associated with rapid neutralization of the thrombin formation, since TFPI inhibits the complex of TF/VIIa/Ca(2+). The manifestation of the above suggestions is the correct TAT complexes and D-dimer, which indicates a low grade of prothrombotic risk in this group of patients, but a higher risk of vascular complications. PMID- 26365122 TI - Invasive fungal infection in allogeneic hematopoietic stem cell transplant recipients: single center experiences of 12 years. AB - Invasive fungal infection (IFI) is a growing cause of morbidity and mortality among patients after allogeneic hematopoietic stem cell transplantation (allo HSCT). We retrospectively reviewed the records of 408 patients undergoing allo HSCTs during the period November 1998 to December 2009, analyzed the incidence and risk factors of IFI, and examined the impact of IFI on overall survival. A total of 92 (22.5%) episodes suffered proven or probable IFI (4 patients were proven, 88 patients were probable). Candida was the most common pathogen for early IFI, and mold was the most frequent causative organism for late IFI. A prior history of IFI, human leukocyte antigen (HLA) mismatch, long-time neutropenia, and acute graft-versus-host-disease (GVHD) were risk factors for early IFI. A prior history of IFI, corticosteroid therapy, cytomegalovirus (CMV) disease, and chronic GVHD were risk factors for late IFI. IFI-related mortality was 53.26%. The 12-year overall survival (OS) rate for IFI was significantly lower than that of patients without IFI (41.9% vs. 63.6%, P<0.01). PMID- 26365123 TI - Reflux characteristics of 113 GERD patients with abnormal 24-h multichannel intraluminal impedance-pH tests. AB - OBJECTIVE: To analyze reflux parameters by means of combined multichannel intraluminal impedance and pH (MII-pH) monitoring in patients with gastroesophageal reflux disease (GERD) symptoms off medication, and to find the reflux characteristics of Chinese GERD patients and the influences of gender, age, body posture, and body mass index (BMI) on gastroesophageal reflux (GER). METHODS: Between Dec. 2008 and May 2014, 125 patients with typical GERD symptoms were subjected to 24-h MII-pH monitoring. Twelve patients with normal MII-pH profiles were not considered for analysis. The reflux parameters of 113 GERD patients with abnormal MII-pH results were analyzed. RESULTS: (1) DeMeester scores were above the normal range in 46.90% (53/113) of GERD patients. Weakly acidic refluxes were prevalent in GERD patients, and the frequency of abnormal weakly acidic reflux was 75.22% (85/113). The frequencies of abnormal symptom index (SI) and symptom association probability (SAP) were 19.47% (22/113) and 14.16% (16/113), respectively. (2) The frequencies of DeMeester scores, the %time at pH<4, and the numbers of reflux episodes and of long reflux episodes >5 min were significantly higher in male patients than in female patients. (3) The %time at pH<4 was much higher during upright periods than during supine periods. During supine periods, 31.86% (36/113) of GERD patients had delayed bolus clearance time, compared with 19.47% (22/113) during upright periods. (4) The number of abnormal DeMeester scores, %time at pH<4, and the number of acid refluxes during upright periods were significantly higher in obese GERD patients than in GERD patients with a normal BMI. Overweight GERD patients also had many more acid refluxes during upright periods than GERD patients with a normal BMI. CONCLUSIONS: Weakly acidic refluxes were prevalent in Chinese GERD patients. The factors male, gender, upright position, obesity (BMI>=25), but not age, may increase the frequency and severity of GER. PMID- 26365124 TI - A discussion on "Tea and human health: biomedical functions of tea active components and current issues". PMID- 26365125 TI - Enhanced emotional empathy after psychosocial stress in young healthy men. AB - Empathy is a core prerequisite for human social behavior. Relatively, little is known about how empathy is influenced by social stress and its associated neuroendocrine alterations. The current study was designed to test the impact of acute stress on emotional and cognitive empathy. Healthy male participants were exposed to a psychosocial laboratory stressor (trier social stress test, (TSST)) or a well-matched control condition (Placebo-TSST). Afterwards they participated in an empathy test measuring emotional and cognitive empathy (multifaceted empathy test, (MET)). Stress exposure caused an increase in negative affect, a rise in salivary alpha amylase and a rise in cortisol. Participants exposed to stress reported more emotional empathy in response to pictures displaying both positive and negative emotional social scenes. Cognitive empathy (emotion recognition) in contrast did not differ between the stress and the control group. The current findings provide initial evidence for enhanced emotional empathy after acute psychosocial stress. PMID- 26365126 TI - Design principles for engaging and retaining virtual citizen scientists. AB - Citizen science initiatives encourage volunteer participants to collect and interpret data and contribute to formal scientific projects. The growth of virtual citizen science (VCS), facilitated through websites and mobile applications since the mid-2000s, has been driven by a combination of software innovations and mobile technologies, growing scientific data flows without commensurate increases in resources to handle them, and the desire of internet connected participants to contribute to collective outputs. However, the increasing availability of internet-based activities requires individual VCS projects to compete for the attention of volunteers and promote their long-term retention. We examined program and platform design principles that might allow VCS initiatives to compete more effectively for volunteers, increase productivity of project participants, and retain contributors over time. We surveyed key personnel engaged in managing a sample of VCS projects to identify the principles and practices they pursued for these purposes and led a team in a heuristic evaluation of volunteer engagement, website or application usability, and participant retention. We received 40 completed survey responses (33% response rate) and completed a heuristic evaluation of 20 VCS program sites. The majority of the VCS programs focused on scientific outcomes, whereas the educational and social benefits of program participation, variables that are consistently ranked as important for volunteer engagement and retention, were incidental. Evaluators indicated usability, across most of the VCS program sites, was higher and less variable than the ratings for participant engagement and retention. In the context of growing competition for the attention of internet volunteers, increased attention to the motivations of virtual citizen scientists may help VCS programs sustain the necessary engagement and retention of their volunteers. PMID- 26365127 TI - Functional architectures based on self-assembly of bio-inspired dipeptides: Structure modulation and its photoelectronic applications. AB - Getting inspiration from nature and further developing functional architectures provides an effective way to design innovative materials and systems. Among bio inspired materials, dipeptides and its self-assembled architectures with functionalities have recently been the subject of intensive studies. However, there is still a great challenge to explore its applications likely due to the lack of effective adaptation of their self-assembled structures as well as a lack of understanding of the self-assembly mechanisms. In this context, taking diphenylalanine (FF, a core recognition motif for molecular self-assembly of the Alzheimer's beta-amyloid polypeptides) as a model of bio-inspired dipeptides, recent strategies on modulation of dipeptide-based architectures were introduced with regard to both covalent (architectures modulation by coupling functional groups) and non-covalent ways (controlled architectures by different assembly pathways). Then, applications are highlighted in some newly emerging fields of innovative photoelectronic devices and materials, such as artificial photosynthetic systems for renewable solar energy storage and renewable optical waveguiding materials for optoelectronic devices. At last, the challenges and future perspectives of these bio-inspired dipeptides are also addressed. PMID- 26365128 TI - The complete mitogenome of lesser striped shrew Sorex bedfordiae (soricidae). AB - The Sorex genus is type genus in Soricidae. Most of them lack comprehensive biological data. In this study, the complete mitochondrial genome sequence of Sorex bedfordiae was determined. The mitogenome is 17 160 base pairs in length and contains 13 protein-coding genes, two ribosomal RNA genes, 22 transfer RNA genes, and one control region. The nucleotide sequence data of 12 heavy-strand protein-coding genes of Sorex bedfordiae and other 10 species in Soricidae were used for phylogenetic analyses. Tree constructed using Bayesian phylogenetic methods demonstrated Sorex bedfordiae as a sister to Sorex cylindricauda. Phylogenetic analyses further confirmed that Blarinella diverged prior to Sorex and Anourosorex, but Episoriculus differentiated earlier than Neomys and Nectogale within subfamily Soricinae. PMID- 26365129 TI - Measuring Participation for Children and Youth With Power Mobility Needs: A Systematic Review of Potential Health Measurement Tools. AB - OBJECTIVES: To identify and critically appraise potential participation measurement tools for children aged 18 months to 17 years with power mobility (PM) needs. DATA SOURCES: Searches in 9 electronic databases identified peer reviewed publications in English to January 2015, along with hand-searching included bibliographies. STUDY SELECTION: The Preferred Reporting Items for Systematic reviews and Meta-Analyses statement was followed with inclusion criteria set a priori. Keywords and subject headings included participation and measurement terms with descriptors of young people who are potential PM candidates. Publications describing measurement properties of English-language tools were included if the items included >= 85% content related to participation and described at least 2 participation dimensions. DATA EXTRACTION: Two reviewers reached consensus after independently screening titles and abstracts, identifying full-text articles meeting criteria, extracting data, and conducting quality ratings. Tool descriptions, clinical utility, and measurement properties were extracted. Study quality and measurement properties were evaluated using the COnsensus-based Standards for the selection of health Measurement INstruments checklist and the McMaster Outcome Measures Rating Form. DATA SYNTHESIS: Of 1330 titles identified, 138 peer-reviewed publications met study inclusion criteria. Fifty tools were identified, of which 20 met inclusion criteria. Evidence supporting reliability and validity varied considerably. Two tools had responsiveness evidence, an important measurement property when evaluating change. Quality ratings were strongest for internal consistency and content validity. Ratings were downgraded because of small sample sizes and a limited description of missing data or study conditions. CONCLUSIONS: While potential tools emerged (Assessment of Preschool Children's Participation, Preferences for Activities of Children, Child and Adolescent Scale of Participation, Child Engagement in Daily Life, Canadian Occupational Performance Measure, Questionnaire of Young People's Participation), none were judged best suited for use with children having PM needs. Further empirical studies with this population are needed before recommending use for PM applications. PMID- 26365131 TI - Is delirium being detected in emergency? AB - OBJECTIVE: To report on the use of Delirium Care Pathways to screen for and recognise delirium by Aged Care Services in Emergency Teams (ASETs) at five metropolitan hospitals in New South Wales, Australia. Knowledge of delirium and the use of Delirium Care Pathways are vital to ensure that older people presenting with delirium receive best practice care. METHODS: An audit of 205 randomly selected medical records of clients over 65 years presenting to an ASET was conducted. RESULTS: Delirium was recorded in the medical records notes of four clients (2%). However, the auditors identified another 27 clients with symptoms of delirium. CONCLUSIONS: Delirium is still frequently undiagnosed and misdiagnosed in older people presenting to emergency departments. This indicates a need for further education and professional development for and by health-care practitioners. Only with greater awareness of delirium will the care and health outcomes of older adults presenting with delirium in acute care settings improve. PMID- 26365130 TI - The general movement optimality score: a detailed assessment of general movements during preterm and term age. AB - AIM: To explore the appropriateness of applying a detailed assessment of general movements and characterize the relationship between global and detailed assessment. METHOD: The analysis was based on 783 video recordings of 233 infants (154 males, 79 females) who had been videoed from 27 to 45 weeks postmenstrual age. Apart from assessing the global general movement categories (normal, poor repertoire, cramped-synchronized, or chaotic general movements), we scored the amplitude, speed, spatial range, proximal and distal rotations, onset and offset, tremulous and cramped components of the upper and lower extremities. Applying the optimality concept, the maximum general movement optimality score of 42 indicates the optimal performance. RESULTS: General movement optimality scores (GMOS) differentiated between normal general movements (median 39 [25-75th centile 37 41]), poor repertoire general movements (median 25 [22-29]), and cramped synchronized general movements (median 12 [10-14]; p<0.01). The optimality score for chaotic general movements (mainly occurring at late preterm age) was similar to those for cramped-synchronized general movements (median 14 [12-17]). Short lasting tremulous movements occurred from very preterm age (<32wks) to post-term age across all general movement categories, including normal general movements. The detailed score at post-term age was slightly lower compared to the scores at preterm and term age for both normal (p=0.02) and poor repertoire general movements (p<0.01). INTERPRETATION: Further research might demonstrate that the GMOS provides a solid base for the prediction of improvement versus deterioration within an individual general movement trajectory. PMID- 26365132 TI - Anti-inflammatory effects of eugenol nanoemulsion as a topical delivery system. AB - Eugenol is the main constituent of clove oil with anti-inflammatory properties. In this work, for the first time, O/W nanoemulsion of eugenol was designed for the evaluation of anti-inflammatory effects as a topical delivery system. Topical formulations containing 1%, 2% and 4% of eugenol as well as a nanoemulsion system containing 4% eugenol and 0.5% piroxicam were prepared. Further to physicochemical examinations, such as determination of particle size, polydispersity index, zeta potential and physical stability, anti-inflammatory activity was examined in carrageenan-induced paw edema in rats. The optimum formulation was found to contain 2% eugenol (oil phase), 14% Tween 20 (surfactant) and 14% isopropyl alcohol (co-surfactant) in water. Nanoemulsion with polydispersity index of 0.3 and median droplet diameter of 24.4 nm (d50) was obtained. Animal studies revealed that the nanoemulsions exhibited significantly improved anti-inflammatory activity after 1.5 h, compared with marketed piroxicam gel. Additionally, it was shown that increasing the concentration of eugenol did not show higher inhibition of inflammation. Also, the nanoemulsion having piroxicam showed less anti-inflammatory properties compared with the nanoemulsion without piroxicam. PMID- 26365133 TI - Factors affecting recall rate and false positive fraction in breast cancer screening with breast tomosynthesis - A statistical approach. AB - In this study, we investigate which factors affect the false positive fraction (FPF) for digital breast tomosynthesis (DBT) compared to digital mammography (DM) in a screening population by using classification and regression trees (C&RT) and binary marginal generalized linear models. The data was obtained from the Malmo Breast Tomosynthesis Screening Trial, which aimed to compare the performance of DBT to DM in breast cancer screening. By using data from the first half of the study population (7500 women), a tree with the recall probability for different groups was calculated. The effect of age and breast density on the FPF was estimated using a binary marginal generalized linear model. Our results show that breast density and breast cancer were the main factors influencing recall. The FPF is mainly affected by breast density and increases with breast density for DBT and DM. In conclusion, the results obtained with C&RT are easy to interpret and similar to those obtained using binary marginal generalized linear models. The FPF is approximately 40% higher for DBT compared to DM for all breast density categories. PMID- 26365134 TI - Interfacial pattern selection in miscible liquids under vibration. AB - We explore the peculiar behaviour of an interface between two miscible liquids of similar (but non-identical) viscosities and densities under horizontal vibration with a frequency less than 25 Hz. Significant differences in the structure of the formed patterns were found between microgravity and ground experiments. In a gravity field, a spatially periodic saw-tooth frozen structure is generated in the interface which dissipates at long times. By contrast, under the low gravity conditions of a parabolic flight, the long lived pattern consists of a series of vertical columns of alternating liquids. PMID- 26365135 TI - Congenital thrombotic thrombocytopenic purpura: Upshaw-Schulman syndrome: a cause of neonatal death and review of literature. AB - Thrombotic thrombocytopenic purpura (TTP) is a rare disorder in children characterized by microangiopathic hemolytic anemia (MAHA) and thrombocytopenia. The classic Moschcowitz Pentads of TTP include hemolytic anemia, with fragmentation of erythrocytes, thrombocytopenia, diffuse and non-focal neurologic findings, decrease renal function and fever. We report a newborn who was diagnosed with congenital TTP. The newborn was admitted at age of 40 h, in our hospital, in view of respiratory distress with impending respiratory failure and red colored urine. On examination, the newborn was febrile, tachypneic, had deep icterus, pallor and no hepatosplenomegaly. Family history was significant with one unexplained neonatal death at age of 24 with symptoms of red colored urine. Examination of peripheral smear was diagnostic with the presence of fragmented RBCS, giant but fewer platelets consistent with a diagnosis of MAHA. The diagnosis of TTP was confirmed with low ADAMTS activity and gene analysis showed c 2203 G > T-p.Glu735X (domain TSP1-2) mutation in exon 18 of ADAMTS 13 gene. The newborn had rapid deterioration, with respiratory distress and refractory shock leading to death. Post-mortem bone marrow done showed marrow hyperplasia. PMID- 26365136 TI - The relationship between sleep and cognition in Parkinson's disease: A meta analysis. AB - It is well established that sleep disorders have neuropsychological consequences in otherwise healthy people. Studies of night-time sleep problems and cognition in Parkinson's disease (PD), however, paint a mixed picture, with many reporting no relationship between sleep problems and neuropsychological performance. This review aimed to meta-analyse this research and to examine the factors underlying these mixed results. A literature search was conducted of published and unpublished studies, resulting in 16 papers that met inclusion criteria. Data were analysed in the domains of: global cognitive function; memory (general, long term verbal recognition, long-term verbal recall); and executive function (general, shifting, updating, inhibition, generativity, fluid reasoning). There was a significant effect of sleep on global cognitive function, long-term verbal recall, long-term verbal recognition, shifting, updating, generativity, and fluid reasoning. Although there are effects on memory and executive function associated with poor sleep in PD, the effects were driven by a small number of studies. Numerous methodological issues were identified. Further studies are needed reliably to determine whether disturbed sleep impacts on cognition via mechanisms of hypoxia, hypercapnia, sleep fragmentation, chronic sleep debt or decreased REM and/or slow wave sleep in PD, as this may have important clinical implications. PMID- 26365137 TI - GABA Receptors: Pharmacological Potential and Pitfalls. AB - Gamma-amino butyric acid (GABA), the major inhibitory neurotransmitter in the mammalian central nervous system, plays a key role in the regulation of neuronal transmission throughout the brain, affecting numerous physiological and psychological processes. Changes in GABA levels provoke disbalance between excitatory and inhibitory signals, and are involved in the development of numerous neuropsychiatric disorders. GABA exerts its effects via ionotropic (GABAA) and metabotropic (GABAB) receptors. Both types of receptors are targeted by many clinically important drugs that affect GABAergic function and are widely used in the treatment of anxiety disorder, epilepsy, insomnia, spasticity, aggressive behaviour, and other pathophysiological conditions and diseases. Of particular importance are drugs that modulate GABAA receptor complex, such as benzodiazepines, barbiturates, neuroactive steroids, intravenous and inhalational anesthetics, and ethanol. Molecular interactions and subsequent pharmacological effects induced by drugs acting at GABAA receptors are extremely complex due to structural heterogeneity of GABAA receptors and existence of numerous allosterically interconnected binding sites and various chemically distinct ligands that are able to bound to them. There is a growing interest in the development and application of subtype-selective drugs that will achieve specific therapeutic benefits without undesirable side effects. The aim of this review is to briefly summarize the key pharmacological properties of GABA receptors, and to present selected novel findings with the potential to open new perspectives in the development of more effective therapeutic strategies. PMID- 26365138 TI - The GABAergic System and the Gastrointestinal Physiopathology. AB - Since the first report about the presence of gamma-aminobutyric acid (GABA) within the gastrointestinal (GI) tract, accumulating evidence strongly supports the widespread representation of the GABAergic system in the enteric milieu, underlining its potential multifunctional role in the regulation of GI functions in health and disease. GABA and GABA receptors are widely distributed throughout the GI tract, constituting a complex network likely regulating the diverse GI behaviour patterns, cooperating with other major neurotransmitters and mediators for maintaining GI homeostasis in physiologic and pathologic conditions. GABA is involved in the circuitry of the enteric nervous system, controlling GI secretion and motility, as well as in the GI endocrine system, possibly acting as a autocrine/paracrine or hormonal agent. Furthermore, a series of investigations addresses the GABAergic system as a potential powerful modulator of GI visceral pain processing, enteric immune system and carcinogenesis. Although overall such actions may imply the consideration of the GABAergic system as a novel therapeutic target in different GI pathologic states, including GI motor and secretory diseases and different enteric inflammatory- and pain-related pathologies, current clinical applications of GABAergic drugs are scarce. Thus, in an attempt to propel novel scientific efforts addressing the detailed characterization of the GABAergic signaling in the GI tract, and consequently the development of novel strategies for the treatment of different GI disorders, we reviewed and discussed the current evidence about GABA actions in the enteric environment, with a particular focus on their possible therapeutic implications. PMID- 26365139 TI - GABAergic Modulation in Diabetic Encephalopathy-Related Depression. AB - Central nervous system is not spared from the deleterious effects of diabetes, since several studies have described neuropsychological and neurobehavioral changes in diabetic subjects, suggesting that diabetic encephalopathy should be recognized as a complication of this complex metabolic disorder. In fact, psychiatric manifestations may accompany this encephalopathy, since the prevalence of depression in diabetic patients is much higher than in the general population. Furthermore, evidences from preclinical and clinical studies suggest that GABA plays a role both in the pathophysiology of the diabetic encephalopathy related depression. So, this review addresses the GABAergic modulation in diabetic encephalopathy-related depression. Data presented from literature support the association between GABA and depressive- like behaviors in diabetic encephalopathy, being this neurotransmitter a potential target for the treatment of diabetes, depression and related comorbidities. PMID- 26365140 TI - Treatment Options in Alzheimer's Disease: The GABA Story. AB - Alzheimer's disease (AD) is the most common form of dementia in the elderly. Research focused on identifying compounds that restore cognition and memory in AD patients is a very active investigational pursuit, but unfortunately, it has been only successful in terms of developing symptomatic treatments. Abeta deposition and neurofibrillary tangles along with neuron and synapse loss are associated with neurotransmitter dysfunction and have been recognized as hallmarks of AD. Furthermore, clinical and preclinical studies point to this neurotransmitter dysfunction as a main factor underlying both cognitive and neuropsychiatric symptoms of the illness. Cholinergic deficit in AD prompted the use of cholinesterase inhibitors as the symptomatic treatment of cognitive decline in AD, however this therapeutic approach provides only modest benefit in the majority of patients. Hence, nowadays research is focused on investigating compounds that could restore cognition and memory in AD patients. GABA is the primary inhibitory neurotransmitter in the central nervous system and GABAergic neurons provide extensive innervation to cholinergic and glutamatergic neurons. It has been shown that dysfunction of the GABAergic system may contribute to cognitive impairment in humans. Significant reductions in GABA levels have been described in severe cases of AD, which could be underlying the behavioral and psychological symptoms of AD. This review examines the involvement of the GABAergic system in both cognitive and non-cognitive behavioural symptoms in AD, providing some pointers for rational drug development. PMID- 26365142 TI - GABAergic Pharmacotherapy in the Treatment of Motor Disorders of the Central Nervous System. AB - Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the central nervous system, and diseases that associate a deficiency in GABA might benefit from GABAergic drugs. Cerebellar Purkinje cells employ GABA as a neurotransmitter. Cortical cerebellar atrophy (CCA) shows Purkinje cell loss, and ataxia caused by it was alleviated by gabapentin and pregabalin. Thus, CCA is proposed as a model of selective deficiency in GABA in the cerebellum, which benefits clinically from administration of GABAergic drugs, in a manner similar in which levodopa improves motor manifestations in Parkinson's disease. Other ataxias also benefited clinically from GABAergic drugs, as adult-onset GM2 gangliosidosis, olivopontocerebellar atrophy, cerebellar ataxia with hypogonadism, spinocerebellar ataxias 1, 2 and 6, and adult-onset ataxia telangiectasia. Complex neurochemical diseases, as multiple-system atrophy, had ataxia worsened by GABAergic drugs. Various disorders with a deficiency in GABA content had their manifestations relieved by admistration of GABAergic drugs, as one patient with progressive encephalomyelitis with rigidity, whose muscular spasms were suppressed by a combination of gabapentin and tiagabine, and another with diaphragmatic myoclonus, who required gabapentin and tiagabine for symptomatic control. On the contrary, GABAergic drugs were not effective in cervical dystonia, amyotrophic lateral sclerosis, Parkinson's disease and progressive supranuclear palsy, presumably because a deficiency in GABA is not an essential neurochemical abnormality in these diseases. Research aimed at identifying effective therapies to treat cerebellar ataxias and other motor disorders of the central nervous system is warranted. Meanwhile, therapeutic tests with GABAergic drugs might yield clinical improvement in these diseases. PMID- 26365143 TI - A compact planar low-energy-gap molecule with a donor-acceptor-donor nature based on a bimetal dithiolene complex. AB - We present the first report of a compact, planar and low-energy-gap molecule based on a pi-conjugated bimetal system comprising a tetrathiooxalate (tto) skeleton. The observed low HOMO-LUMO energy gap (1.19 eV) is attributed to its donor-acceptor-donor (D-A-D) nature because the skeleton acts as an electron acceptor as well as a tiny and noninnocent bridging moiety. PMID- 26365141 TI - Advances in the Understanding of the Gabaergic Neurobiology of FMR1 Expanded Alleles Leading to Targeted Treatments for Fragile X Spectrum Disorder. AB - Fragile X spectrum disorder (FXSD) includes: fragile X syndrome (FXS), fragile X associated tremor ataxia syndrome (FXTAS) and fragile X-associated primary ovarian insufficiency (FXPOI), as well as other medical, psychiatric and neurobehavioral problems associated with the premutation and gray zone alleles. FXS is the most common monogenetic cause of autism (ASD) and intellectual disability (ID). The understanding of the neurobiology of FXS has led to many targeted treatment trials in FXS. The first wave of phase II clinical trials in FXS were designed to target the mGluR5 pathway; however the results did not show significant efficacy and the trials were terminated. The advances in the understanding of the GABA system in FXS have shifted the focus of treatment trials to GABA agonists, and a new wave of promising clinical trials is under way. Ganaxolone and allopregnanolone (GABA agonists) have been studied in individuals with FXSD and are currently in phase II trials. Both allopregnanolone and ganaxolone may be efficacious in treatment of FXS and FXTAS, respectively. Allopregnanolone, ganaxolone, riluzole, gaboxadol, tiagabine, and vigabatrin are potential GABAergic treatments. The lessons learned from the initial trials have not only shifted the targeted system, but also have refined the design of clinical trials. The results of these new trials will likely impact further clinical trials for FXS and other genetic disorders associated with ASD. PMID- 26365144 TI - Extracorporeal shockwaves versus ultrasound-guided percutaneous lavage for the treatment of rotator cuff calcific tendinopathy: a randomized controlled trial. AB - BACKGROUND: Extracorporeal shockwave treatment (ESWT) and ultrasound-guided percutaneous lavage (UGPL) are two effective ways of treating rotator cuff calcific tendinopathy (RCCT). AIM: The aim of the present study was to compare the effectiveness of these techniques in the treatment of RCCT. DESIGN: Prospective, randomized, controlled trial. SETTING: Patients treated in our sports medicine and rehabilitation center (Centro Medico Deyre, Madrid. Spain) between January 2007 and December 2013. METHODS: This randomized study compares the results achieved with these techniques over one year following their use to treat the above condition. Eighty patients received ESWT and 121 received UGPL. A visual analogue scale was used to measure pain, and ultrasound to determine the extent of calcification, at 3, 6, and 12 months after treatment. RESULTS: Pain and the amount of calcification were significantly reduced by both techniques at 3, 6 and 12 months (P<0.001 for each), but significantly more so by UGPL (P<0.001). CONCLUSIONS: Both techniques are valid for the treatment of RCCT, although UGPL is associated with a greater reduction of calcification and greater reduction in pain. CLINICAL REHABILITATION IMPACT: The results obtained applying UGPL, the low cost and the lack of complications should therefore make the treatment of choice in centers that are appropriately equipped and staffed. PMID- 26365145 TI - The positive role of caregivers in terminal cancer patients' abilities: usefulness of the ICF framework. AB - BACKGROUND: Among the purposes of palliative care, reducing perceived disability during the terminal stages of illness is of paramount importance. AIM: The aim of this study was to shed light on the possible role of the caregiver as a modulator of disability in patients with advanced cancer receiving end-of-life palliative care by means of the WHO International Classification of Functioning, Disability and Health (ICF). DESIGN: Observational prospective cross-sectional study. SETTING: Inpatients of a Palliative Care Unit. POPULATION: Fifty consecutively enrolled inpatients (aged 69.9+/-10.6), in bed on average for more than 50% of daily hours (Karnofsky Performance Status Scale: 31.2+/-10.0) and functionally severely compromised (Barthel Index: 45.3+/-19.7); the average estimated survival was 6 weeks or more (Palliative Prognostic Index: 5.5+/-2.4). METHODS: Inpatients compiled a self-report questionnaire on quality of life (SF-12) and were interviewed on the ICF checklist. RESULTS: Patients reported significantly lower quality of life scores (SF-12) than the normative sample for both the Physical Component Summary Score (29.2+/-8.1 vs. 50.0+/-9.4; Student's t-test P=0.00001) and the Mental Component Summary Score (39.7+/-11.8 vs. 50.0+/-9.9; P=0.01). As to ICF Activity and Participation delta (Delta) values, describing caregiver's impact on patient's life: 26 domains had a median Delta=0 (neutral caregiver's role), 10 domains had a median Delta>0 (caregiver as a positive modulator of the patient's disability); no negative Delta values were reported (caregiver never considered as a barrier). Environmental Factors were mainly facilitators. CONCLUSIONS: Even if patients were mostly confined to bed, with reduced functional autonomy and marked dependency on others, their disability was reduced thanks to the caregiver's modulator role. CLINICAL REHABILITATION IMPACT: The ICF framework could also be extended to palliative care, because by integrating the standard functional assessment, it allows to identify two levels of intervention: one directly affecting patients' activity and participation, and one related to barriers and facilitators (i.e., caregivers, environmental factors). PMID- 26365146 TI - Hyaluronic acid intra-articular injection and exercise therapy: effects on pain and disability in subjects affected by lower limb joints osteoarthritis. A systematic review by the Italian Society of Physical and Rehabilitation Medicine (SIMFER). AB - BACKGROUND: It is debated whether intra-articular viscosupplementation with hyaluronic acid (HA) can lead to improvements in subjects with osteoarthritis (OA) undergoing physical and rehabilitative interventions. AIM: To assess the effects of intra-articular viscosupplementation on disability in subjects with OA undergoing physical and rehabilitative interventions. Information on pain and quality of life were also collected. METHODS: The databases of PubMed, Medline, EMbase and CINAHL were searched for English language full-text randomized controlled trials comparing intra-articular viscosupplementation alone or associated with physical and rehabilitative interventions to viscosupplementation alone, shame treatment, waiting lists, and any type of rehabilitative interventions. Methodological quality of each study was assessed by using the Physiotherapy Evidence Database (PEDro) Scale. RESULTS: A total of 115 references were retrieved, and 8 studies were selected. Three trials compared HA injection and physical therapy in knee OA, with disability and pain improvements in all studies, and between-group differences in favor of physical therapy in two studies; two trials compared HA injection and home exercises in knee OA, with improvements in pain, disability and quality of life in all studies, without between-group differences; two trials compared HA injection plus physical therapy agents and exercises to exercises plus physical therapy agents in knee OA, with improvements in disability and pain in both studies, and between-group differences in favor of the inclusion HA in one study; one trial compared HA injection and home exercises in ankle OA, with improvements in disability and pain in both arms without between-group differences. CONCLUSION: Physical therapy agents seemed to have greater effects than intra-articular viscosupplementation on disability and pain. In the other cases both intra-articular viscosupplementation and physical and rehabilitative interventions seemed to be equally effective in improving disability, pain, and quality of life in subjects with knee and ankle OA. CLINICAL REHABILITATION IMPACT: A treatment model associating intra-articular viscosupplementation to physical and rehabilitative interventions seems promising but more high quality RCTs are needed before it can be suggested. PMID- 26365147 TI - High serum carotenoids associated with lower risk for the metabolic syndrome and its components among Japanese subjects: Mikkabi cohort study. AB - Recent epidemiological studies show the association of carotenoids with the metabolic syndrome (MetS), but thorough longitudinal cohort studies regarding this association have not been well conducted. The objective of this study was to investigate longitudinally whether serum carotenoids are associated with the risk of developing the MetS and its components in Japanese subjects. We conducted a follow-up study on 1073 men and women aged 30-79 years at the baseline from the Mikkabi prospective cohort study. Those who participated in the baseline and completed follow-up surveys were examined longitudinally. Over the 10-year period, 910 subjects (295 men and 615 women) took part in the follow-up survey at least once. Over a mean follow-up period of 7.8 (sd 2.9) years, thirty-six men and thirty-one women developed new MetS. After adjustments for confounders, the hazard ratio (HR) for the MetS in the highest tertile of serum beta-carotene against the lowest tertile was 0.47 (95 % CI 0.23, 0.95). On the other hand, significantly lower risks for dyslipidaemia were observed in the highest tertiles of serum alpha- and beta-carotene and beta-cryptoxanthin (HR 0.66; 95 % CI 0.46, 0.96; HR, 0.54; 95 % CI 0.37, 0.79; and HR 0.66; 95 % CI 0.44, 0.99, respectively). Other significant associations between the risks for obesity, high blood pressure and hyperglycaemia with serum carotenoids were not observed. Our results further support the hypothesis that eating a diet rich in carotenoids might help prevent the development of the MetS and its complications in Japanese subjects. PMID- 26365149 TI - Extensively burns patients are not unsuitable candidates to vascularized composite allotransplantations but require optimization in access to suitable transplants. PMID- 26365148 TI - Chronic Alcohol Exposure is Associated with Decreased Neurogenesis, Aberrant Integration of Newborn Neurons, and Cognitive Dysfunction in Female Mice. AB - BACKGROUND: Neurological deficits of alcohol use disorder (AUD) have been attributed to dysfunctions of specific brain structures. Studies of alcoholic patients and chronic alcohol exposure animal models consistently identify reduced hippocampal mass and cogntive dysfunctions as a key alcohol-induced brain adaptation. However, the precise substrate of chronic alcohol exposure that leads to structural and functional impairments of the hippocampus is largely unknown. METHODS: Using a calorie-matched alcohol feeding method, we tested whether chronic alcohol exposure targets neural stem cells and neurogenesis in the adult hippocampus. The effect of alcohol on proliferation of neural stem cells as well as cell fate determination and survival of newborn cells was evaluated via bromodeoxyuridine pulse and chase methods. A retrovirus-mediated single-cell labeling method was used to determine the effect of alcohol on the morphological development and circuitry incorporation of individual hippocampal newborn neurons. Finally, novel object recognition (NOR) and Y-maze tests were performed to examine whether disrupted neurogenesis is associated with hippocampus dependent functional deficits in alcohol-fed mice. RESULTS: Chronic alcohol exposure reduced proliferation of neural stem cells and survival rate of newborn neurons; however, the fate determination of newborn cells remained unaltered. Moreover, the dendritic spine density of newborn neurons significantly decreased in alcohol-fed mice. Impaired spine formation indicates that alcohol interfered the synaptic connectivity of newborn neurons with excitatory neurons originating from various areas of the brain. In the NOR test, alcohol-fed mice displayed deficits in the ability to discriminate the novel object. CONCLUSIONS: Our study revealed that chronic alcohol exposure disrupted multiple steps of neurogenesis, including the production and development of newborn neurons. In addition, chronic alcohol exposure altered connectivity of newborn neurons with other input neurons. Decreased neurogenesis and aberrant integration of newborn neurons into hippocampal networks are closely associated with deficits in hippocampus dependent cognitive functions of alcohol-fed mice. PMID- 26365150 TI - Breast metastasis and lung large-cell neuroendocrine carcinoma: first clinical observation. AB - BACKGROUND AND AIMS: The lung large-cell neuroendocrine carcinoma (LCNEC) is a very rare aggressive neuroendocrine tumor with a high propensity to metastasize and very poor prognosis. We report an atypical presentation of lung LCNEC was diagnosed from a metastatic nodule on the breast. METHODS: Our patient is a 59 years-old woman that presented in March 2014 nonproductive cough. A CT scan showed multiple brain, lung, adrenal gland and liver secondary lesions; moreover, it revealed a breast right nodule near the chest measuring 1.8 cm. The breast nodule and lung lesions were biopsied and their histology and molecular diagnosis were LCNEC of the lung. To our knowledge, this is the first documented case of breast metastasis from LCNEC of the lung. RESULTS: Furthermore, breast metastasis from extramammary malignancy is uncommon and its diagnosis is difficult but important for proper management and prediction of prognosis. Therefore, a careful clinical history with a thorough clinical examination is needed to make the correct diagnosis. Moreover, metastasis to the breast should be considered in any patient with a known primary malignant tumor history who presents with a breast lump. Anyhow, pathological examination should be performed to differentiate the primary breast cancer from metastatic tumor. CONCLUSION: Therefore, an accurate diagnosis of breast metastases may not only avoid unnecessary breast resection, more importantly it is crucial to determine an appropriate and systemic treatment. PMID- 26365151 TI - Establishment and characterization of a new conditionally immortalized human astrocyte cell line. AB - Astrocytes are the most abundant cell types in mammalian brains, within which they participate in various neuronal activities, partly by utilizing the numerous transporters expressed at their plasma membranes. Accordingly, detailed characterization of astrocytic functions, including transporters, are essential for understanding of mechanistic basis of normal brain functions, as well as the pathogenesis and treatment of various brain diseases. As a part of overall efforts to facilitate such studies, this study reports on the establishment of a new human astrocyte cell line, which is hereafter referred to as human astrocyte/conditionally immortalized, clone 35 (HASTR/ci35). This line, which was developed utilizing a cell immortalization method, showed excellent proliferative ability and expressed various astrocyte markers, including glial fibrillary acidic protein. When co-cultured with neuronal cells, HASTR/ci35 cells could facilitate their dendritic network formation. Furthermore, HASTR/ci35 cells not only possessed significant glutamate and adenosine transporter activities but also exhibited organic ion transporter activities. To summarize, HASTR/ci35 cells possess several key astrocytic characteristics, including various transporter functions, while simultaneously showing infinite proliferation and scalability. Based on these findings, HASTR/ci35 cells can be expected to contribute significantly to various human astrocyte study fields. In vitro astrocyte models are valuable experimental tools in various astrocyte studies. Here, we report the establishment of a new human astrocyte cell line, HASTR/ci35, which show various key astrocyte properties, including astrocytic transporter activities, glycogen storage and facilitation of neuronal cell differentiation. Thus, HASTR/ci35 is expected to significantly contribute to advances toward detailed understanding of human astrocyte functions. PMID- 26365152 TI - The phenotypic equilibrium of cancer cells: From average-level stability to path wise convergence. AB - The phenotypic equilibrium, i.e. heterogeneous population of cancer cells tending to a fixed equilibrium of phenotypic proportions, has received much attention in cancer biology very recently. In the previous literature, some theoretical models were used to predict the experimental phenomena of the phenotypic equilibrium, which were often explained by different concepts of stabilities of the models. Here we present a stochastic multi-phenotype branching model by integrating conventional cellular hierarchy with phenotypic plasticity mechanisms of cancer cells. Based on our model, it is shown that: (i) our model can serve as a framework to unify the previous models for the phenotypic equilibrium, and then harmonizes the different kinds of average-level stabilities proposed in these models; and (ii) path-wise convergence of our model provides a deeper understanding to the phenotypic equilibrium from stochastic point of view. That is, the emergence of the phenotypic equilibrium is rooted in the stochastic nature of (almost) every sample path, the average-level stability just follows from it by averaging stochastic samples. PMID- 26365153 TI - Risk Factors for Acute and Chronic Graft-versus-Host Disease after Allogeneic Hematopoietic Cell Transplantation with Umbilical Cord Blood and Matched Sibling Donors. AB - Allogeneic hematopoietic cell transplantation is often complicated by graft versus-host disease (GVHD). We analyzed the incidences and risk factors for acute (aGVHD) and chronic GVHD (cGVHD), and their impact on disease relapse and survival, among recipients of single umbilical cord blood (sUCB, n = 295), double umbilical cord blood (dUCB, n = 416), and matched sibling donor (MSD, n = 469) allografts. The incidences of grades II to IV aGVHD and chronic GVHD among dUCB, sUCB, and MSD were 56% and 26%, 26% and 7%, 37% and 40%, respectively. Development of aGVHD had no effect on relapse, nonrelapse mortality, or overall survival among cord blood recipients, but it was associated with worse nonrelapse mortality and survival in MSD recipients. Development of cGVHD was only associated with lower relapse in dUCBT. In multivariate analysis of GVHD incidence, age > 18 years was associated with higher incidence of aGVHD and cGVHD across all cohorts. In both UCB cohorts worse HLA match and prior aGVHD were associated with higher risks of aGVHD and cGVHD, respectively. Nonmyeloablative conditioning limited the risk of aGVHD compared with myeloablative conditioning in dUCB recipients. Cyclosporine A and mycophenolate mofetil as GVHD prophylaxis lowered the risk of cGVHD, compared with steroids with cyclosporine A, among sUCB recipients. This large contemporary analysis suggests distiinct risks and consequences of GVHD for UCB and MSD recipients. Limiting the severity of aGVHD remains important in all groups. Increasing the cord blood inventory or developing strategies that reduce the cell-dose threshold and thereby increase the chance of identifying an adequately dosed, better HLA-matched sUCB unit may further limit risks of aGVHD after UCB transplantation. PMID- 26365154 TI - Pediatric Vasculitis. AB - Vasculitis is defined as inflammation of the blood vessels and can result in stenosis or aneurysm, which may in turn lead to occlusion or rupture of the vessel compromising tissue perfusion. The manifestations of these diseases depend on the size and site of the vessels effected. Vasculitis can be secondary to numerous inflammatory and infectious diseases but this review will concentrate on the systemic primary vasculitides and aims to discuss the presentations and approaches to management of a number of these conditions. PMID- 26365155 TI - Sick Neonate Score--A Simple Clinical Score for Predicting Mortality of Sick Neonates in Resource Restricted Settings. AB - OBJECTIVE: To evaluate an objective score to assess the condition of sick neonates at arrival and its use in predicting mortality. METHODS: This descriptive study included 303 extramural neonates who were evaluated using a simple clinical score - Sick neonate score (SNS). All neonates were followed up till discharge or expiry. The score and its individual components were correlated with outcome. A receiver operating curve was plotted to determine the cutoff value for SNS in predicting mortality. RESULTS: The common indications for neonatal transport were sepsis (30.7 %), birth asphyxia (17.5 %) and respiratory distress (15.2 %). Sixty neonates (20 %) expired and among them 76 % were hypothermic and 10 % hypoglycemic at admission. The average SNS for all neonates was 10 while it was 6 for those who expired. A cutoff value of SNS <= 8 predicted mortality with a sensitivity of 58.3 % and specificity of 52.7 %. CONCLUSIONS: SNS is a useful scoring system to predict outcome of sick neonates in resource restricted settings. PMID- 26365156 TI - Plasma Folate, Vitamin B12 and Homocysteine Levels in Children with Solid Tumors at Diagnosis; Results from a Pediatric Referral Centre. PMID- 26365157 TI - Editorial: What Does the Pediatrician Needs to Know About Heart Defects in Children? PMID- 26365158 TI - Congenital Disorder of Glycosylation (CDG) Presenting as Non-immune Hydrops Fetalis. PMID- 26365160 TI - Cold antibody autoimmune haemolytic anaemia in a child with diffuse large B cell lymphoma. PMID- 26365159 TI - Comprehensive urinary metabolomic profiling and identification of potential noninvasive marker for idiopathic Parkinson's disease. AB - Urine metabolic phenotyping has been associated with the development of Parkinson's disease (PD). However, few studies using a comprehensive metabolomics approach have investigated the correlation between changes in the urinary markers and the progression of clinical symptoms in PD. A comprehensive metabolomic study with robust quality control procedures was performed using gas chromatography - mass spectrometry (GC - MS) and liquid chromatography - mass spectrometry (LC - MS) to characterize the urinary metabolic phenotypes of idiopathic PD patients at three stages (early, middle and advanced) and normal control subjects, with the aim of discovering potential urinary metabolite markers for the diagnosis of idiopathic PD. Both GC-MS and LC-MS metabolic profiles of idiopathic PD patients differed significantly from those of normal control subjects. 18 differentially expressed metabolites were identified as constituting a unique metabolic marker associated with the progression of idiopathic PD. Related metabolic pathway variations were observed in branched chain amino acid metabolism, glycine derivation, steroid hormone biosynthesis, tryptophan metabolism, and phenylalanine metabolism. Comprehensive, successive metabolomic profiling revealed changes in the urinary markers associated with progression of idiopathic PD. This profiling relies on noninvasive sampling, and is complementary to existing clinical modalities. PMID- 26365161 TI - ERIC-PCR genotyping of field isolates of Salmonella enterica subsp. enterica serovar Gallinarum biovars Gallinarum and Pullorum. AB - Salmonella Gallinarum (SG) and Salmonella Pullorum (SP) have been classified as biovars belonging to Salmonella enterica subsp. enterica serovar Gallinarum. Genetic diversity among isolates of the same biovar can be detected by DNA fingerprinting techniques which are useful in epidemiological investigations. In this study, we applied the PCR amplification of Enterobacterial Repetitive Intergenic Consensus sequences (ERIC-PCR) to analyse 45 strains of SG and SP, most of which were isolated from diseased poultry of different Brazilian regions over a period of 27 years until 2014. The ERIC-genotypes obtained were used to describe the epidemiological relationship amongst the strains. Our findings showed that there were six ERIC-patterns for SG strains at 80% similarity. In addition, some of the SG isolates recovered from different regions and years clustered with 100% similarity, suggesting that transfer of genotypes between these regions has taken place. The commercial rough vaccine strain 9R showed a unique profile. Meanwhile, more genetic diversity was observed among SP strains where ten ERIC-patterns were also formed at 80% similarity. PMID- 26365162 TI - SNPs in candidate genes MX dynamin-like GTPase and chemokine (C-C motif) receptor 5 are associated with ovine pulmonary adenocarcinoma progression in Latxa sheep. AB - Ovine pulmonary adenocarcinoma (OPA) is a contagious lung cancer in sheep caused by Jaagsiekte sheep retrovirus (JSRV). OPA is present in many sheep-rearing countries causing economic and welfare issues, as currently no efficient vaccines or treatments are available. Breed differences suggest a host genetic component may influence the pathogenesis of OPA, but so far few genes have been identified. In this work, a genetic association study was carried out in Latxa dairy sheep which were classified as cases/controls based on the presence/absence of OPA lung tumours. Candidate genes included cytokines and a receptor and innate immunity genes. After SNPs in the candidate genes were identified, the distribution of alleles in cases and controls was compared by means of logistic regression analyses at the allelic, genotypic and haplotypic levels. The association analysis showed that several candidate genes were significantly associated with resistance or susceptibility to OPA; two of the candidates, CCR5 and MX1, remained significantly associated with resistance and susceptibility respectively, even after Bonferroni correction. PMID- 26365163 TI - Improving the efficiency of polymer solar cells based on furan-flanked diketopyrrolopyrrole copolymer via solvent additive and methanol treatment. AB - We present a furan-flanked DPP copolymer, poly{3,6-difuran-2-yl-2,5-di(2 octyldodecyl)-pyrrolo [3,4-c]pyrrole-1,4-dione-altthienylenevinylene} (PDVF-8), and highlight the improvement in the power conversion efficiency (PCE) of polymer solar cells (PSCs) based on the PDVF-8 as an electron donor via solvent additive and methanol treatment. When 3 vol% 1,8-diiodooctane (DIO) or 1-chloronaphthalene (CN) were used as a solvent additive to the PDVF-8:PC71BM solution in chloroform (CF), the PCE can increase from 0.79% to 3.73% or 4.26%. Methanol treatment (MT) can further enhance the PCE to 4.03% (DIO) and 4.69% (CN). The effect of the solvent additives (DIO and CN) and MT on the phase separation of the PDVF 8:PC71BM thin film has been investigated in detail using atomic force microscopy, transmission electron microscopy (TEM), TEM-energy dispersive spectroscopy and X ray photoemission spectroscopy depth profiling. PMID- 26365164 TI - Metoprolol improves survival in severe traumatic brain injury independent of heart rate control. AB - BACKGROUND: Multiple prior studies have suggested an association between survival and beta-blocker administration in patients with severe traumatic brain injury (TBI). However, it is unknown whether this benefit of beta-blockers is dependent on heart rate control. The aim of this study was to assess whether rate control affects survival in patients receiving metoprolol with severe TBI. Our hypothesis was that improved survival from beta-blockade would be associated with a reduction in heart rate. METHODS: We performed a 7-y retrospective analysis of all blunt TBI patients at a level-1 trauma center. Patients aged >16 y with head abbreviated injury scale 4 or 5, admitted to the intensive care unit (ICU) from the operating room or emergency room (ER), were included. Patients were stratified into two groups: metoprolol and no beta-blockers. Using propensity score matching, we matched the patients in two groups in a 1:1 ratio controlling for age, gender, race, admission vital signs, Glasgow coma scale, injury severity score, mean heart rate monitored during ICU admission, and standard deviation of heart rate during the ICU admission. Our primary outcome measure was mortality. RESULTS: A total of 914 patients met our inclusion criteria, of whom 189 received beta-blockers. A propensity-matched cohort of 356 patients (178: metoprolol and 178: no beta-blockers) was created. Patients receiving metoprolol had higher survival than those patients who did not receive beta-blockers (78% versus 68%; P = 0.04); however, there was no difference in the mean heart rate (89.9 +/- 13.9 versus 89.9 +/- 15; P = 0.99). Nor was there a difference in the mean of standard deviation of the heart rates (14.7 +/- 6.3 versus 14.4 +/- 6.5; P = 0.65) between the two groups. In Kaplan-Meier survival analysis, patients who received metoprolol had a survival advantage (P = 0.011) compared with patients who did not receive any beta-blockers. CONCLUSIONS: Our study shows an association with improved survival in patients with severe TBI receiving metoprolol, and this effect appears to be independent of any reduction in heart rate. We suggest that beta-blockers should be administered to all severe TBI patients irregardless of any perceived beta-blockade effect on heart rate. PMID- 26365166 TI - Rapid first-line discrimination of methicillin resistant Staphylococcus aureus strains using MALDI-TOF MS. AB - Fast and reliable discrimination of methicillin-resistant Staphylococcus aureus (MRSA) isolates is essential in identifying an outbreak. Molecular typing methods, such as S. aureus protein A (spa) typing, multi locus sequence typing (MLST) and pulse field gel electrophoresis (PFGE) are generally used for this purpose. These methods are all relatively time-consuming and not performed routinely in all laboratories. The aim of this study is to examine whether MALDI TOF MS can be used as a fast, simple and easily implemented method for first-line discrimination of MRSA isolates. Mass spectra from 600 clinical MRSA isolates were included in the study, representing 89 spa types, associated with 16 different known clonal complexes. All spectra were obtained directly from colony material obtained from overnight cultures without prior protein extraction. We identified 43 useful discriminatory m/z-values (peaks) and used a concept of arranging these peaks into pairs or small clusters within a small mass range, allowing for quality control of the spectra obtained. Using this concept we could reproducibly characterise and arrange the isolates into 26 MALDI-TOF groups, which strongly correlated with spa types and clonal complexes. The results of this study clearly show that MALDI-TOF MS can be used for first-line discrimination of MRSA isolates, using a simple and fast method that is easy to implement as part of routine testing. PMID- 26365165 TI - Superresolution Pattern Recognition Reveals the Architectural Map of the Ciliary Transition Zone. AB - The transition zone (TZ) of primary cilia serves as a diffusion barrier to regulate ciliogenesis and receptor localization for key signaling events such as sonic hedgehog signaling. Its gating mechanism is poorly understood due to the tiny volume accommodating a large number of ciliopathy-associated molecules. Here we performed stimulated emission depletion (STED) imaging of collective samples and recreated superresolved relative localizations of eight representative species of ciliary proteins using position averages and overlapped with representative electron microscopy (EM) images, defining an architectural foundation at the ciliary base. Upon this framework, transmembrane proteins TMEM67 and TCTN2 were accumulated at the same axial level as MKS1 and RPGRIP1L, suggesting that their regulation roles for tissue-specific ciliogenesis occur at a specific level of the TZ. CEP290 is surprisingly localized at a different axial level bridging the basal body (BB) and other TZ proteins. Upon this molecular architecture, two reservoirs of intraflagellar transport (IFT) particles, correlating with phases of ciliary growth, are present: one colocalized with the transition fibers (TFs) while the other situated beyond the distal edge of the TZ. Together, our results reveal an unprecedented structural framework of the TZ, facilitating our understanding in molecular screening and assembly at the ciliary base. PMID- 26365167 TI - Fluorescence in situ hybridization for the identification of Treponema pallidum in tissue sections. AB - Syphilis is often called the great imitator because of its frequent atypical clinical manifestations that make the disease difficult to recognize. Because Treponema pallidum subsp. pallidum, the infectious agent of syphilis, is yet uncultivated in vitro, diagnosis is usually made using serology; however, in cases where serology is inconclusive or in patients with immunosuppression where these tests may be difficult to interpret, the availability of a molecular tool for direct diagnosis may be of pivotal importance. Here we present a fluorescence in situ hybridization (FISH) assay that simultaneously identifies and analyzes spatial distribution of T. pallidum in histological tissue sections. For this assay the species-specific FISH probe TPALL targeting the 16S rRNA of T. pallidum was designed in silico and evaluated using T. pallidum infected rabbit testicular tissue and a panel of non-syphilis spirochetes as positive and negative controls, respectively, before application to samples from four syphilis-patients. In a HIV positive patient, FISH showed the presence of T. pallidum in inguinal lymph node tissue. In a patient not suspected to suffer from syphilis but underwent surgery for phimosis, numerous T. pallidum cells were found in preputial tissue. In two cases with oral involvement, FISH was able to differentiate T. pallidum from oral treponemes and showed infection of the oral mucosa and tonsils, respectively. The TPALL FISH probe is now readily available for in situ identification of T. pallidum in selected clinical samples as well as T. pallidum research applications and animal models. PMID- 26365168 TI - Rapid detection of cefotaxime-resistant Escherichia coli by LC-MS. AB - Antibiotic resistance is an unsolved healthcare problem with increasing impact on patient management in the last years. In particular, multidrug resistance among Gram-negative bacterial strains has become the most pressing challenge. In order to deliver the most efficacious antimicrobial therapy with minimum delay, rapid diagnostic tests are required in order to detect multidrug resistant pathogens early during infection. In line with these efforts, we have developed a mass spectrometry-based assay for the rapid determination of ampicillin and cefotaxime resistance. The assay quantifies beta-lactamase activities towards ampicillin and cefotaxime within a turnaround time of 150 min, which is substantially faster than classical susceptibility testing. PMID- 26365169 TI - Effects of polysaccharide intercellular adhesin (PIA) in an ex vivo model of whole blood killing and in prosthetic joint infection (PJI): A role for C5a. AB - BACKGROUND: A major complication of using medical devices is the development of biofilm-associated infection caused by Staphylococcus epidermidis where polysaccharide intercellular adhesin (PIA) is a major mechanism of biofilm accumulation. PIA affects innate and humoral immunity in isolated cells and animal models. Few studies have examined these effects in prosthetic joint infection (PJI). METHODS: This study used ex vivo whole blood modelling in controls together with matched-serum and staphylococcal isolates from patients with PJI. RESULTS: Whole blood killing of PIA positive S. epidermidis and its isogenic negative mutant was identical. Differences were unmasked in immunosuppressed whole blood pre-treated with dexamethasone where PIA positive bacteria showed a more resistant phenotype. PIA expression was identified in three unique patterns associated with bacteria and leukocytes, implicating a soluble form of PIA. Purified PIA reduced whole blood killing while increasing C5a levels. In clinically relevant staphylococcal isolates and serum samples from PJI patients; firstly complement C5a was increased 3-fold compared to controls; secondly, the C5a levels were significantly higher in serum from PJI patients whose isolates preferentially formed PIA-associated biofilms. CONCLUSIONS: These data demonstrate for the first time that the biological effects of PIA are mediated through C5a in patients with PJI. PMID- 26365170 TI - Intrabody application of eptotermin alpha enhances bone formation in osteoporotic fractures of the lumbar spine; however, fails to increase biomechanical stability - results of an experimental sheep model. AB - This study analyses the effect of eptotermin alpha application into fractured vertebrae. It is hypothesized that eptotermin alpha is capable to enhance bony healing of the osteoporotic spine. In 10 Merino sheep osteoporosis induction was performed by ovariectomy, corticosteroid therapy and calcium/phosphorus/vitamin D deficient diet; followed by standardized creation of lumbar vertebral compression fractures (VCFs) type A3.1 and consecutive fracture reduction/fixation using expandable mesh cages. Randomly, intravertebral eptotermin alpha (G1) or no augmentation was added (G2). Macroscopic, micro-CT, and biomechanical evaluation assessed bony consolidation two months postoperatively: Micro-CT data revealed bony consolidation for all cases with significant increased callus development for G2 (60%) and BV/TV (bone volume/total volume 73.45%, osteoporotic vertebrae 35.76%). Neither group showed improved biomechanical stability. Eptotermin alpha enhanced mineralisation in VCFs in an experimental setup with use of cementless augmentation via an expandable cage. However, higher bone mineral density did not lead to superior biomechanical properties. PMID- 26365171 TI - Behavioral Genetics and the Forensic Mental Health Provider: An Overview. AB - The area of behavioral genetics has sufficiently entered the area of forensic mental health work that providers should have some working knowledge of the strengths and limitations of these exciting technical advances. Using MAOA as an example, this essay reviews some of the recurring themes in forensic behavioral genetics and suggests additional ways in which the technology might be used in legal matters. PMID- 26365174 TI - Cleft palate caused by congenital teratoma. AB - A cleft palate results from incomplete fusion of the lateral palatine processes, the median nasal septum and the median palatine process. This case report describes a rare case of congenital teratoma originating from the nasal septum that may have interfered with the fusion of the palatal shelves during embryonic development, resulting in a cleft palate. An infant girl was born at 40 weeks of gestation weighing 3020 g with a complete cleft palate associated with a large central nasopharyngeal tumour. Computed tomography (CT) of the head showed a well defined mass of mixed density. The tumour was attached to the nasal septum in direct contact with the cleft palate. A biopsy confirmed the teratoma. Tumour resection was performed at 5 months, soft palate reconstruction at 7 months and hard palate closure at 14 months. There was no sign of local recurrence 1 year later. Most teratomas are benign and the prognosis is usually good. However, recurrence is not rare if germ cell carcinomatous foci are present within the teratoma. For these reasons, we advocate the use of a two-stage procedure in which closure of the cleft palate is postponed until histological examination confirms complete excision of the teratoma. PMID- 26365173 TI - Active Inference, homeostatic regulation and adaptive behavioural control. AB - We review a theory of homeostatic regulation and adaptive behavioural control within the Active Inference framework. Our aim is to connect two research streams that are usually considered independently; namely, Active Inference and associative learning theories of animal behaviour. The former uses a probabilistic (Bayesian) formulation of perception and action, while the latter calls on multiple (Pavlovian, habitual, goal-directed) processes for homeostatic and behavioural control. We offer a synthesis these classical processes and cast them as successive hierarchical contextualisations of sensorimotor constructs, using the generative models that underpin Active Inference. This dissolves any apparent mechanistic distinction between the optimization processes that mediate classical control or learning. Furthermore, we generalize the scope of Active Inference by emphasizing interoceptive inference and homeostatic regulation. The ensuing homeostatic (or allostatic) perspective provides an intuitive explanation for how priors act as drives or goals to enslave action, and emphasises the embodied nature of inference. PMID- 26365175 TI - Genetic variants of the autophagy pathway as prognostic indicators for prostate cancer. AB - Autophagy is a complex process of autodigestion in conditions of cellular stress, and it might play an important role in the pathophysiology during carcinogenesis. We hypothesize that genetic variants of the autophagy pathway may influence clinical outcomes in prostate cancer patients. We genotyped 40 tagging single nucleotide polymorphisms (SNPs) from 7 core autophagy pathway genes in 458 localized prostate cancer patients. Multivariate Cox regression was performed to evaluate the independent association of each SNP with disease progression. Positive findings were then replicated in an independent cohort of 504 advanced prostate cancer patients. After adjusting for known clinicopathologic factors, the association between ATG16L1 rs78835907 and recurrence in localized disease [hazard ratio (HR) 0.70, 95% confidence interval (CI) 0.54-0.90, P = 0.006] was replicated in more advanced disease (HR 0.78, 95% CI 0.64-0.95, P = 0.014). Additional integrated in silico analysis suggests that rs78835907 tends to affect ATG16L1 expression, which in turn is correlated with tumor aggressiveness and patient prognosis. In conclusion, genetic variants of the autophagy pathway contribute to the variable outcomes in prostate cancer, and discovery of these novel biomarkers might help stratify patients according to their risk of disease progression. PMID- 26365176 TI - MYC/PGC-1alpha Balance Determines the Metabolic Phenotype and Plasticity of Pancreatic Cancer Stem Cells. AB - The anti-diabetic drug metformin targets pancreatic cancer stem cells (CSCs), but not their differentiated progenies (non-CSCs), which may be related to distinct metabolic phenotypes. Here we conclusively demonstrate that while non-CSCs were highly glycolytic, CSCs were dependent on oxidative metabolism (OXPHOS) with very limited metabolic plasticity. Thus, mitochondrial inhibition, e.g., by metformin, translated into energy crisis and apoptosis. However, resistant CSC clones eventually emerged during treatment with metformin due to their intermediate glycolytic/respiratory phenotype. Mechanistically, suppression of MYC and subsequent increase of PGC-1alpha were identified as key determinants for the OXPHOS dependency of CSCs, which was abolished in resistant CSC clones. Intriguingly, no resistance was observed for the mitochondrial ROS inducer menadione and resistance could also be prevented/reversed for metformin by genetic/pharmacological inhibition of MYC. Thus, the specific metabolic features of pancreatic CSCs are amendable to therapeutic intervention and could provide the basis for developing more effective therapies to combat this lethal cancer. PMID- 26365178 TI - MSC Transplantation Improves Osteopenia via Epigenetic Regulation of Notch Signaling in Lupus. AB - Mesenchymal stem cell transplantation (MSCT) has been used to treat human diseases, but the detailed mechanisms underlying its success are not fully understood. Here we show that MSCT rescues bone marrow MSC (BMMSC) function and ameliorates osteopenia in Fas-deficient-MRL/lpr mice. Mechanistically, we show that Fas deficiency causes failure of miR-29b release, thereby elevating intracellular miR-29b levels, and downregulates DNA methyltransferase 1 (Dnmt1) expression in MRL/lpr BMMSCs. This results in hypomethylation of the Notch1 promoter and activation of Notch signaling, in turn leading to impaired osteogenic differentiation. Furthermore, we show that exosomes, secreted due to MSCT, transfer Fas to recipient MRL/lpr BMMSCs to reduce intracellular levels of miR-29b, which results in recovery of Dnmt1-mediated Notch1 promoter hypomethylation and thereby improves MRL/lpr BMMSC function. Collectively our findings unravel the means by which MSCT rescues MRL/lpr BMMSC function through reuse of donor exosome-provided Fas to regulate the miR-29b/Dnmt1/Notch epigenetic cascade. PMID- 26365177 TI - Metabolic and Non-Cognitive Manifestations of Alzheimer's Disease: The Hypothalamus as Both Culprit and Target of Pathology. AB - Alzheimer's disease (AD) is increasingly recognized as a complex neurodegenerative disease beginning decades prior to the cognitive decline. While cognitive deficits remain the cardinal manifestation of AD, metabolic and non cognitive abnormalities, such as alterations in body weight and neuroendocrine functions, are also present, often preceding the cognitive decline. Furthermore, hypothalamic dysfunction can also be a driver of AD pathology. Here we offer a brief appraisal of hypothalamic dysfunction in AD and provide insight into an underappreciated dual role of the hypothalamus as both a culprit and target of AD pathology, as well as into new opportunities for therapeutic interventions and biomarker development. PMID- 26365179 TI - PDK1-Dependent Metabolic Reprogramming Dictates Metastatic Potential in Breast Cancer. AB - Metabolic reprogramming is a hallmark of cellular transformation, yet little is known about metabolic changes that accompany tumor metastasis. Here we show that primary breast cancer cells display extensive metabolic heterogeneity and engage distinct metabolic programs depending on their site of metastasis. Liver metastatic breast cancer cells exhibit a unique metabolic program compared to bone- or lung-metastatic cells, characterized by increased conversion of glucose derived pyruvate into lactate and a concomitant reduction in mitochondrial metabolism. Liver-metastatic cells displayed increased HIF-1alpha activity and expression of the HIF-1alpha target Pyruvate dehydrogenase kinase-1 (PDK1). Silencing HIF-1alpha reversed the glycolytic phenotype of liver-metastatic cells, while PDK1 was specifically required for metabolic adaptation to nutrient limitation and hypoxia. Finally, we demonstrate that PDK1 is required for efficient liver metastasis, and its expression is elevated in liver metastases from breast cancer patients. Our data implicate PDK1 as a key regulator of metabolism and metastatic potential in breast cancer. PMID- 26365181 TI - Problems in the diagnosis of discordant atrioventricular with concordant ventriculo-arterial connections: anatomical considerations, surgical management, and long-term outcome. AB - BACKGROUND: Discordant atrioventricular with concordant ventriculo-arterial connections is a rare cardiac defect. When isolated, the haemodynamics resemble transposition of the great arteries. In complex heart defects such as heterotaxy, haemodynamics guide the surgical approach. OBJECTIVE: To report a series of eight patients with discordant atrioventricular and concordant ventriculo-arterial connections focussing on anatomical and diagnostic difficulties, surgical management, and follow-up. METHODS: A retrospective review was carried out from 1983 to 2013. Anatomical description was based on segmental analysis. Emphasis was placed on the venoatrial connections. RESULTS: Segmental arrangement was {I, D, S} in six patients, all with spiralling great vessels. There were two patients with parallel great vessels of whom one had {S, L, D} and the other had {S, L, A} arrangement. Of eight patients, five had heterotaxy syndrome. Median age at repair surgery was 1.4 years (with a range from 1.1 months to 8.1 years). The repair surgery finally performed was the atrial switch procedure in seven out of eight patients. The main post-operative complications were two cases of baffle obstruction and one sick sinus syndrome needing pacemaker implantation. There were two early post-operative deaths and six late survivors. Median follow-up was 4.2 years (with a range from 3.9 to 26.7 years) with good functional status in all survivors. Discussion Diagnosing discordant atrioventricular with concordant ventriculo-arterial connections remains challenging. There are ongoing controversies about the definition of atrial morphology and heterotaxy syndrome animating the anatomic discussion of these complex heart defects. Haemodynamically, the atrial switch procedure is the surgical method of choice with an encouraging long-term follow-up despite rhythm disturbances and baffle obstruction. PMID- 26365180 TI - Hepatic Bmal1 Regulates Rhythmic Mitochondrial Dynamics and Promotes Metabolic Fitness. AB - Mitochondria undergo architectural/functional changes in response to metabolic inputs. How this process is regulated in physiological feeding/fasting states remains unclear. Here we show that mitochondrial dynamics (notably fission and mitophagy) and biogenesis are transcriptional targets of the circadian regulator Bmal1 in mouse liver and exhibit a metabolic rhythm in sync with diurnal bioenergetic demands. Bmal1 loss-of-function causes swollen mitochondria incapable of adapting to different nutrient conditions accompanied by diminished respiration and elevated oxidative stress. Consequently, liver-specific Bmal1 knockout (LBmal1KO) mice accumulate oxidative damage and develop hepatic insulin resistance. Restoration of hepatic Bmal1 activities in high-fat-fed mice improves metabolic outcomes, whereas expression of Fis1, a fission protein that promotes quality control, rescues morphological/metabolic defects of LBmal1KO mitochondria. Interestingly, Bmal1 homolog AHA-1 in C. elegans retains the ability to modulate oxidative metabolism and lifespan despite lacking circadian regulation. These results suggest clock genes are evolutionarily conserved energetics regulators. PMID- 26365182 TI - Off-Target V(D)J Recombination Drives Lymphomagenesis and Is Escalated by Loss of the Rag2 C Terminus. AB - Genome-wide analysis of thymic lymphomas from Tp53(-/-) mice with wild-type or C terminally truncated Rag2 revealed numerous off-target, RAG-mediated DNA rearrangements. A significantly higher fraction of these errors mutated known and suspected oncogenes/tumor suppressor genes than did sporadic rearrangements (p < 0.0001). This tractable mouse model recapitulates recent findings in human pre-B ALL and allows comparison of wild-type and mutant RAG2. Recurrent, RAG-mediated deletions affected Notch1, Pten, Ikzf1, Jak1, Phlda1, Trat1, and Agpat9. Rag2 truncation substantially increased the frequency of off-target V(D)J recombination. The data suggest that interactions between Rag2 and a specific chromatin modification, H3K4me3, support V(D)J recombination fidelity. Oncogenic effects of off-target rearrangements created by this highly regulated recombinase may need to be considered in design of site-specific nucleases engineered for genome modification. PMID- 26365183 TI - TCF1 Is Required for the T Follicular Helper Cell Response to Viral Infection. AB - T follicular helper (TFH) and T helper 1 (Th1) cells generated after viral infections are critical for the control of infection and the development of immunological memory. However, the mechanisms that govern the differentiation and maintenance of these two distinct lineages during viral infection remain unclear. We found that viral-specific TFH and Th1 cells showed reciprocal expression of the transcriptions factors TCF1 and Blimp1 early after infection, even before the differential expression of the canonical TFH marker CXCR5. Furthermore, TCF1 was intrinsically required for the TFH cell response to viral infection; in the absence of TCF1, the TFH cell response was severely compromised, and the remaining TCF1-deficient TFH cells failed to maintain TFH-associated transcriptional and metabolic signatures, which were distinct from those in Th1 cells. Mechanistically, TCF1 functioned through forming negative feedback loops with IL-2 and Blimp1. Our findings demonstrate an essential role of TCF1 in TFH cell responses to viral infection. PMID- 26365185 TI - CD103(+) Dendritic Cells Control Th17 Cell Function in the Lung. AB - Th17 cells express diverse functional programs while retaining their Th17 identity, in some cases exhibiting a stem-cell-like phenotype. Whereas the importance of Th17 cell regulation in autoimmune and infectious diseases is firmly established, the signaling pathways controlling their plasticity are undefined. Using a mouse model of invasive pulmonary aspergillosis, we found that lung CD103(+) dendritic cells (DCs) would produce IL-2, dependent on NFAT signaling, leading to an optimally protective Th17 response. The absence of IL-2 in DCs caused unrestrained production of IL-23 and fatal hyperinflammation, which was characterized by strong Th17 polarization and the emergence of a Th17 stem cell-like population. Although several cell types may be affected by deficient IL 2 production in DCs, our findings identify the balance between IL-2 and IL-23 productions by lung DCs as an important regulator of the local inflammatory response to infection. PMID- 26365184 TI - TNF Counterbalances the Emergence of M2 Tumor Macrophages. AB - Cancer can involve non-resolving, persistent inflammation where varying numbers of tumor-associated macrophages (TAMs) infiltrate and adopt different activation states between anti-tumor M1 and pro-tumor M2 phenotypes. Here, we resolve a cascade causing differential macrophage phenotypes in the tumor microenvironment. Reduction in TNF mRNA production or loss of type I TNF receptor signaling resulted in a striking pattern of enhanced M2 mRNA expression. M2 gene expression was driven in part by IL-13 from eosinophils co-recruited with inflammatory monocytes, a pathway that was suppressed by TNF. Our data define regulatory nodes within the tumor microenvironment that balance M1 and M2 populations. Our results show macrophage polarization in cancer is dynamic and dependent on the balance between TNF and IL-13, thus providing a strategy for manipulating TAMs. PMID- 26365186 TI - PTPN11 Is a Central Node in Intrinsic and Acquired Resistance to Targeted Cancer Drugs. AB - Most BRAF (V600E) mutant melanomas are sensitive to selective BRAF inhibitors, but BRAF mutant colon cancers are intrinsically resistant to these drugs because of feedback activation of EGFR. We performed an RNA-interference-based genetic screen in BRAF mutant colon cancer cells to search for phosphatases whose knockdown induces sensitivity to BRAF inhibition. We found that suppression of protein tyrosine phosphatase non-receptor type 11 (PTPN11) confers sensitivity to BRAF inhibitors in colon cancer. Mechanistically, we found that inhibition of PTPN11 blocks signaling from receptor tyrosine kinases (RTKs) to the RAS-MEK-ERK pathway. PTPN11 suppression is lethal to cells that are driven by activated RTKs and prevents acquired resistance to targeted cancer drugs that results from RTK activation. Our findings identify PTPN11 as a drug target to combat both intrinsic and acquired resistance to several targeted cancer drugs. Moreover, activated PTPN11 can serve as a biomarker of drug resistance resulting from RTK activation. PMID- 26365187 TI - Dissecting Fission Yeast Shelterin Interactions via MICro-MS Links Disruption of Shelterin Bridge to Tumorigenesis. AB - Shelterin, a six-member complex, protects telomeres from nucleolytic attack and regulates their elongation by telomerase. Here, we have developed a strategy, called MICro-MS (Mapping Interfaces via Crosslinking-Mass Spectrometry), that combines crosslinking-mass spectrometry and phylogenetic analysis to identify contact sites within the complex. This strategy allowed identification of separation-of-function mutants of fission yeast Ccq1, Poz1, and Pot1 that selectively disrupt their respective interactions with Tpz1. The various telomere dysregulation phenotypes observed in these mutants further emphasize the critical regulatory roles of Tpz1-centered shelterin interactions in telomere homeostasis. Furthermore, the conservation between fission yeast Tpz1-Pot1 and human TPP1-POT1 interactions led us to map a human melanoma-associated POT1 mutation (A532P) to the TPP1-POT1 interface. Diminished TPP1-POT1 interaction caused by hPOT1-A532P may enable unregulated telomere extension, which, in turn, helps cancer cells to achieve replicative immortality. Therefore, our study reveals a connection between shelterin connectivity and tumorigenicity. PMID- 26365188 TI - Disabling of the erbB Pathway Followed by IFN-gamma Modifies Phenotype and Enhances Genotoxic Eradication of Breast Tumors. AB - Reversion of the malignant phenotype of erbB2-transformed cells can be driven by anti-erbB2/neu monoclonal antibodies (mAbs), which disrupt the receptor's kinase activity. We examined the biologic effects of IFN-gamma alone or after anti erbB2/neu mAb treatment of erbB2-positive cells. IFN-gamma had no effect on its own. Treatment of the tumors with anti-erbB2/neu mAbs followed by IFN-gamma led to dramatic inhibition of tumor growth in vitro and in vivo with minimal mAb dosing. Sequential therapy enhanced the effects of chemotherapy. Moreover, IFN gamma with mAb treatment of mice with IFNgammaR knockdown tumors did not demonstrate marked synergistic eradication effects, indicating an unexpected role of IFN-gamma on the tumor itself. Additionally, mAb and IFN-gamma treatment also induced immune host responses that enhanced tumor eradication. Biochemical analyses identified loss of Snail expression in tumor cells, reflecting diminution of tumor-stem-cell-like properties as a consequence of altered activity of GSK3-beta and KLF molecules. PMID- 26365189 TI - Emergence of Ebola Virus Escape Variants in Infected Nonhuman Primates Treated with the MB-003 Antibody Cocktail. AB - MB-003, a plant-derived monoclonal antibody cocktail used effectively in treatment of Ebola virus infection in non-human primates, was unable to protect two of six animals when initiated 1 or 2 days post-infection. We characterized a mechanism of viral escape in one of the animals, after observation of two clusters of genomic mutations that resulted in five nonsynonymous mutations in the monoclonal antibody target sites. These mutations were linked to a reduction in antibody binding and later confirmed to be present in a viral isolate that was not neutralized in vitro. Retrospective evaluation of a second independent study allowed the identification of a similar case. Four SNPs in previously identified positions were found in this second fatality, suggesting that genetic drift could be a potential cause for treatment failure. These findings highlight the importance selecting different target domains for each component of the cocktail to minimize the potential for viral escape. PMID- 26365190 TI - Neuronal Regulation of Schwann Cell Mitochondrial Ca(2+) Signaling during Myelination. AB - Schwann cells (SCs) myelinate peripheral neurons to promote the rapid conduction of action potentials, and the process of myelination is known to be regulated by signals from axons to SCs. Given that SC mitochondria are one of the potential regulators of myelination, we investigated whether SC mitochondria are regulated by axonal signaling. Here, we show a purinergic mechanism that sends information from neurons to SC mitochondria during myelination. Our results show that electrical stimulation of rat sciatic nerve increases extracellular ATP levels enough to activate purinergic receptors. Indeed, electrical stimulation of sciatic nerves induces Ca(2+) increases in the cytosol and the mitochondrial matrix of surrounding SCs via purinergic receptor activation. Chronic suppression of this pathway during active myelination suppressed the longitudinal and radial development of myelinating SCs and caused hypomyelination. These results demonstrate a neuron-to-SC mitochondria signaling, which is likely to have an important role in proper myelination. PMID- 26365191 TI - Defined MicroRNAs Induce Aspects of Maturation in Mouse and Human Embryonic-Stem Cell-Derived Cardiomyocytes. AB - Pluripotent-cell-derived cardiomyocytes have great potential for use in research and medicine, but limitations in their maturity currently constrain their usefulness. Here, we report a method for improving features of maturation in murine and human embryonic-stem-cell-derived cardiomyocytes (m/hESC-CMs). We found that coculturing m/hESC-CMs with endothelial cells improves their maturity and upregulates several microRNAs. Delivering four of these microRNAs, miR-125b 5p, miR-199a-5p, miR-221, and miR-222 (miR-combo), to m/hESC-CMs resulted in improved sarcomere alignment and calcium handling, a more negative resting membrane potential, and increased expression of cardiomyocyte maturation markers. Although this could not fully phenocopy all adult cardiomyocyte characteristics, these effects persisted for two months following delivery of miR-combo. A luciferase assay demonstrated that all four miRNAs target ErbB4, and siRNA knockdown of ErbB4 partially recapitulated the effects of miR-combo. In summary, a combination of miRNAs induced via endothelial coculture improved ESC-CM maturity, in part through suppression of ErbB4 signaling. PMID- 26365192 TI - An Alternatively Spliced Bifunctional Localization Signal Reprograms Human Shugoshin 1 to Protect Centrosomal Instead of Centromeric Cohesin. AB - Separation of human sister chromatids involves the removal of DNA embracing cohesin ring complexes. Ring opening occurs by prophase-pathway-dependent phosphorylation and separase-mediated cleavage, with the former being antagonized at centromeres by Sgo1-dependent PP2A recruitment. Intriguingly, prophase pathway signaling and separase's proteolytic activity also bring about centriole disengagement, whereas Sgo1 is again counteracting this licensing step of later centrosome duplication. Here, we demonstrate that alternative splice variants of human Sgo1 specifically and exclusively localize and function either at centromeres or centrosomes. A small C-terminal peptide encoded by exon 9 of SGO1 (CTS for centrosomal targeting signal of human Sgo1) is necessary and sufficient to drive centrosomal localization and simultaneously abrogate centromeric association of corresponding Sgo1 isoforms. Cohesin is shown to be a target of the prophase pathway at centrosomes and protected by Sgo1-PP2A. Accordingly, premature centriole disengagement in response to Sgo1 depletion is suppressed by blocking ring opening of an engineered cohesin. PMID- 26365193 TI - DNA Methylation Dynamics of Germinal Center B Cells Are Mediated by AID. AB - Changes in DNA methylation are required for the formation of germinal centers (GCs), but the mechanisms of such changes are poorly understood. Activation induced cytidine deaminase (AID) has been recently implicated in DNA demethylation through its deaminase activity coupled with DNA repair. We investigated the epigenetic function of AID in vivo in germinal center B cells (GCBs) isolated from wild-type (WT) and AID-deficient (Aicda(-/-)) mice. We determined that the transit of B cells through the GC is associated with marked locus-specific loss of methylation and increased methylation diversity, both of which are lost in Aicda(-/-) animals. Differentially methylated cytosines (DMCs) between GCBs and naive B cells (NBs) are enriched in genes that are targeted for somatic hypermutation (SHM) by AID, and these genes form networks required for B cell development and proliferation. Finally, we observed significant conservation of AID-dependent epigenetic reprogramming between mouse and human B cells. PMID- 26365194 TI - Sox10 Regulates Stem/Progenitor and Mesenchymal Cell States in Mammary Epithelial Cells. AB - To discover mechanisms that mediate plasticity in mammary cells, we characterized signaling networks that are present in the mammary stem cells responsible for fetal and adult mammary development. These analyses identified a signaling axis between FGF signaling and the transcription factor Sox10. Here, we show that Sox10 is specifically expressed in mammary cells exhibiting the highest levels of stem/progenitor activity. This includes fetal and adult mammary cells in vivo and mammary organoids in vitro. Sox10 is functionally relevant, as its deletion reduces stem/progenitor competence whereas its overexpression increases stem/progenitor activity. Intriguingly, we also show that Sox10 overexpression causes mammary cells to undergo a mesenchymal transition. Consistent with these findings, Sox10 is preferentially expressed in stem- and mesenchymal-like breast cancers. These results demonstrate a signaling mechanism through which stem and mesenchymal states are acquired in mammary cells and suggest therapeutic avenues in breast cancers for which targeted therapies are currently unavailable. PMID- 26365195 TI - Cocaine-Induced Endocannabinoid Mobilization in the Ventral Tegmental Area. AB - Cocaine is a highly addictive drug that acts upon the brain's reward circuitry via the inhibition of monoamine uptake. Endogenous cannabinoids (eCB) are lipid molecules released from midbrain dopamine (DA) neurons that modulate cocaine's effects through poorly understood mechanisms. We find that cocaine stimulates release of the eCB, 2-arachidonoylglycerol (2-AG), in the rat ventral midbrain to suppress GABAergic inhibition of DA neurons, through activation of presynaptic cannabinoid CB1 receptors. Cocaine mobilizes 2-AG via inhibition of norepinephrine uptake and promotion of a cooperative interaction between Gq/11 coupled type-1 metabotropic glutamate and alpha1-adrenergic receptors to stimulate internal calcium stores and activate phospholipase C. The disinhibition of DA neurons by cocaine-mobilized 2-AG is also functionally relevant because it augments DA release in the nucleus accumbens in vivo. Our results identify a mechanism through which the eCB system can regulate the rewarding and addictive properties of cocaine. PMID- 26365197 TI - Glucosinolates Are Mainly Absorbed Intact in Germfree and Human Microbiota Associated Mice. AB - Chemoprotective or genotoxic effects of glucosinolates occurring in Brassica vegetables are attributed to their hydrolysis products formed upon tissue damage by plant myrosinase. Since Brassica vegetables, in which myrosinase has been heat inactivated, still display bioactivity, glucosinolate activation has been attributed to intestinal bacteria. The aim of this study was to investigate whether this is true. Glucoraphanin (172 mg/kg body weight) and neoglucobrassicin (297 mg/kg body weight) were administered intragastrically to germ free and human microbiota associated (HMA) mice. Approximately 30% of the applied doses of glucoraphanin and neoglucobrassicin were excreted unchanged in the urine of both germ free and HMA mice. Isothiocyanates, sulforaphane, and erucin, formed from glucoraphanin, were mainly excreted as urinary N-acetyl-l-cysteine conjugates. N Methoxyindole-3-carbinol formed from neoglucobrassicin was observed in small amounts in both germ free and HMA mice. Formation of DNA adducts from neoglucobrassicin was also independent from bacterial colonization of the mice. Hence, intestinal bacteria are involved in the bioactivation of glucosinolates in the gut, but their contribution to glucosinolate transformation in HMA mice is apparently very small. PMID- 26365196 TI - A Circuit for Gradient Climbing in C. elegans Chemotaxis. AB - Animals have a remarkable ability to track dynamic sensory information. For example, the nematode Caenorhabditis elegans can locate a diacetyl odor source across a 100,000-fold concentration range. Here, we relate neuronal properties, circuit implementation, and behavioral strategies underlying this robust navigation. Diacetyl responses in AWA olfactory neurons are concentration and history dependent; AWA integrates over time at low odor concentrations, but as concentrations rise, it desensitizes rapidly through a process requiring cilia transport. After desensitization, AWA retains sensitivity to small odor increases. The downstream AIA interneuron amplifies weak odor inputs and desensitizes further, resulting in a stereotyped response to odor increases over three orders of magnitude. The AWA-AIA circuit drives asymmetric behavioral responses to odor increases that facilitate gradient climbing. The adaptation based circuit motif embodied by AWA and AIA shares computational properties with bacterial chemotaxis and the vertebrate retina, each providing a solution for maintaining sensitivity across a dynamic range. PMID- 26365198 TI - Working memory genetics in schizophrenia and related disorders: An RDoC perspective. AB - Improved classification of mental disorders through neurobiological measures will require a set of traits that map to transdiagnostic subgroups of patients and align with heritable, core psychopathological processes at the center of the disorders of interest. A promising candidate is working memory (WM) function, for which deficits have been reported across multiple diagnostic entities including schizophrenia, bipolar disorder, ADHD, autism, and major depressive disorder. Here we review genetic working memory associations and their brain functional correlates from the perspective of identifying patient subgroups across conventional diagnostic boundaries, explore the utility of multimodal investigations integrating functional information at the neural systems level and explore potential limitations as well as future directions for research. PMID- 26365199 TI - Zn(ii) assisted synthesis of porous salen as an efficient heterogeneous scaffold for capture and conversion of CO2. AB - We have designed a unique strategy to obtain a zinc-salen functionalized porous polymer (Zn@SBMMP) with high zinc content (15.3 wt%) by an easy one-step, cost effective and scalable process, which shows unprecedented catalytic efficiency in the CO2 fixation reaction via cycloaddition of CO2 with epoxides. We hypothesize that a high density of Zn-Schiff base/salen units present in the porous polymer network is responsible for the exceptionally high catalytic performance of Zn@SBMMP. PMID- 26365200 TI - A spheroid toxicity assay using magnetic 3D bioprinting and real-time mobile device-based imaging. AB - An ongoing challenge in biomedical research is the search for simple, yet robust assays using 3D cell cultures for toxicity screening. This study addresses that challenge with a novel spheroid assay, wherein spheroids, formed by magnetic 3D bioprinting, contract immediately as cells rearrange and compact the spheroid in relation to viability and cytoskeletal organization. Thus, spheroid size can be used as a simple metric for toxicity. The goal of this study was to validate spheroid contraction as a cytotoxic endpoint using 3T3 fibroblasts in response to 5 toxic compounds (all-trans retinoic acid, dexamethasone, doxorubicin, 5' fluorouracil, forskolin), sodium dodecyl sulfate (+control), and penicillin-G ( control). Real-time imaging was performed with a mobile device to increase throughput and efficiency. All compounds but penicillin-G significantly slowed contraction in a dose-dependent manner (Z' = 0.88). Cells in 3D were more resistant to toxicity than cells in 2D, whose toxicity was measured by the MTT assay. Fluorescent staining and gene expression profiling of spheroids confirmed these findings. The results of this study validate spheroid contraction within this assay as an easy, biologically relevant endpoint for high-throughput compound screening in representative 3D environments. PMID- 26365203 TI - General practitioner-delivered adherence counseling in asthma: feasibility and usefulness of skills, training and support tools. AB - OBJECTIVE: Poor medication adherence contributes to uncontrolled asthma in primary care. Good doctor-patient communication around adherence increases patients' medication taking but general practitioners (GPs) often feel poorly equipped to provide effective adherence counseling. This study aimed to assess the feasibility and usefulness of adherence counseling training, skills and support tools for GPs. METHODS: Twenty-five GPs enrolled in a 6-month cluster randomized-controlled trial of adherence interventions for asthma were randomized to an intervention delivering personalized adherence discussions. They received 2 hours training in delivering brief, motivational-interviewing-based adherence counseling and were provided with asthma-specific counseling support tools. At baseline, post-training and study end, GPs rated the training, reported confidence/frequency of using counseling skills and satisfaction with their consultations, and commented on support tools. Patients reported their barriers to adherence and rated their GPs empathy at baseline and at 6-months. RESULTS: 96% of GPs rated adherence counseling training as very/extremely useful. At the end of the study (17 +/- 4 months) GPs' confidence in using counseling skills increased, as did the frequency they applied the skills and their satisfaction with consultations. GPs were positive about counseling support tools, stating that they were easy to use and facilitated covering more ground within single consultations. Half the GPs expressed some difficulty implementing counseling due to time constraints. Patients reported good GP empathy and no significant change in adherence barriers. CONCLUSIONS: GPs valued counseling training and support tools. Although implementation was sometimes challenging, GPs reported increased frequency of use and confidence in applying adherence counseling skills, which persisted for 17 months. PMID- 26365202 TI - Calcium-controlled conformational choreography in the N-terminal half of adseverin. AB - Adseverin is a member of the calcium-regulated gelsolin superfamily of actin binding proteins. Here we report the crystal structure of the calcium-free N terminal half of adseverin (iA1-A3) and the Ca(2+)-bound structure of A3, which reveal structural similarities and differences with gelsolin. Solution small angle X-ray scattering combined with ensemble optimization revealed a dynamic Ca(2+)-dependent equilibrium between inactive, intermediate and active conformations. Increasing calcium concentrations progressively shift this equilibrium from a main population of inactive conformation to the active form. Molecular dynamics simulations of iA1-A3 provided insights into Ca(2+)-induced destabilization, implicating a critical role for the A2 type II calcium-binding site and the A2A3 linker in the activation process. Finally, mutations that disrupt the A1/A3 interface increase Ca(2+)-independent F-actin severing by A1 A3, albeit at a lower efficiency than observed for gelsolin domains G1-G3. Together, these data address the calcium dependency of A1-A3 activity in relation to the calcium-independent activity of G1-G3. PMID- 26365201 TI - Management of proton pump inhibitor responsive-esophageal eosinophilia and eosinophilic esophagitis: controversies in treatment approaches. AB - Eosinophilic esophagitis (EoE) is a chronic immune-mediated clinicopathologic disease. The prevalence of EoE is approximately 1/2000 persons, EoE is now the most common cause of food impactions, with healthcare expenditures approaching US$ 1 billion annually. This article will discuss challenges related to proton pump inhibitor responsive esophageal eosinophilia, including distinguishing this condition from EoE and understanding the mechanisms behind the PPI response. For EoE, we will review multiple ongoing debates about treatment and monitoring strategies, including selecting treatment outcomes, optimizing medication formulations, approaching the steroid-refractory patient, conducting dietary elimination, prescribing long-term maintenance therapy and performing esophageal dilation. PMID- 26365204 TI - A Mutation-Positive Child With Megalencephalic Leukoencephalopathy With Subcortical Cysts: Classical Imaging Findings. PMID- 26365205 TI - Association between CD14 gene promoter polymorphisms with serum total-IgE and eosinophil levels in atopic and non-atopic asthma patients in a Chinese Han population. AB - OBJECTIVE: The aim of this study was to investigate the association between CD14 gene promoter SNPs with serum total-IgE and eosinophil levels in atopic asthma and non-atopic asthma in Chinese Han. METHODS: A total of 152 patients with asthma were divided into atopic asthma (n = 100) and non-atopic asthma (n = 52) groups for this study. Six CD14 gene SNPs were analyzed using PCR and gene sequencing. Serum total-IgE and eosinophil levels were measured. The association between genotype frequencies of the CD14 gene loci with total-IgE and eosinophil levels in atopic asthma and non-atopic asthma was evaluated by the ANOVA test method. Hundred and sixteen healthy subjects constitute the control group. RESULTS: We found that serum total-IgE and eosinophil levels were significantly higher in individuals with atopic asthma when compared to individuals with non atopic asthma (p < 0.01). For non-atopic asthma, the total-IgE levels of the heterozygous genotypes were significantly higher than the corresponding levels for the homozygous genotypes in CD14-260C > T, CD-651C > T, CD-911A > C and CD 1247A > G (p < 0.01). In atopic asthma, there was no statistical significance for either serum total-IgE or eosinophil levels among the genotypes of the CD14 gene SNPs. In addition, allele A frequency of CD14-1247A > G was significantly different between the atopic asthma and non-atopic asthma groups (p = 0.025). CONCLUSIONS: There was a statistical association between the serum total-IgE level and the CD14 gene promoter SNPs in the non-atopic asthma group. The eosinophil level was not found to be statistically associated with the CD14 gene promoter SNPs in either the atopic asthma or non-atopic asthma groups. PMID- 26365206 TI - Structure of product-bound SMG1 lipase: active site gating implications. AB - Monoacylglycerol and diacylglycerol lipases are industrially interesting enzymes, due to the health benefits that arise from the consumption of diglycerides compared to the traditional triglyceride oils. Most lipases possess an alpha helix (lid) directly over the catalytic pocket which regulates the activity of the enzyme. Generally, lipases exist in active and inactive conformations, depending on the positioning of this lid subdomain. However, lipase SMG1, a monoacylglycerol and diacylglycerol specific lipase, has an atypical activation mechanism. In the present study we were able to prove by crystallography, in silico analysis and activity tests that only two positions, residues 102 and 278, are responsible for a gating mechanism that regulates the active and inactive states of the lipase, and that no significant structural changes take place during activation except for oxyanion hole formation. The elucidation of the gating effect provided data enabling the rational design of improved lipases with 6-fold increase in the hydrolytic activity toward diacylglycerols, just by providing additional substrate stabilization with a single mutation (F278N or F278T). Due to the conservation of F278 among the monoacylglycerol and diacylglycerol lipases in the Rhizomucor miehei lipase-like family, the gating mechanism described herein might represent a general mechanism applicable to other monoacylglycerol and diacylglycerol lipases as well. Database: Structural data are available in the Protein Data Bank under the accession numbers 4ZRE (F278D mutant) and 4ZRD (F278N mutant). PMID- 26365207 TI - S...O chalcogen bonding in sulfa drugs: insights from multipole charge density and X-ray wavefunction of acetazolamide. AB - Experimental charge density analysis combined with the quantum crystallographic technique of X-ray wavefunction refinement (XWR) provides quantitative insights into the intra- and intermolecular interactions formed by acetazolamide, a diuretic drug. Firstly, the analysis of charge density topology at the intermolecular level shows the presence of exceptionally strong interaction motifs such as a DDAA-AADD (D-donor, A-acceptor) type quadruple hydrogen bond motif and a sulfonamide dimer synthon. The nature and strength of intra-molecular S...O chalcogen bonding have been characterized using descriptors from the multipole model (MM) and XWR. Although pure geometrical criteria suggest the possibility of two intra-molecular S...O chalcogen bonded ring motifs, only one of them satisfies the "orbital geometry" so as to exhibit an interaction in terms of an electron density bond path and a bond critical point. The presence of 'sigma-holes' on the sulfur atom leading to the S...O chalcogen bond has been visualized on the electrostatic potential surface and Laplacian isosurfaces close to the 'reactive surface'. The electron localizability indicator (ELI) and Roby bond orders derived from the 'experimental wave function' provide insights into the nature of S...O chalcogen bonding. PMID- 26365209 TI - Basal cell carcinoma showing surface hyperkeratosis clinically mimicking seborrheic keratosis. PMID- 26365208 TI - MicroRNAs Regulating Signaling Pathways: Potential Biomarkers in Systemic Sclerosis. AB - Systemic sclerosis (SSc) is a multisystem fibrotic and autoimmune disease. Both genetic and epigenetic elements mediate SSc pathophysiology. This review summarizes the role of one epigenetic element, known as microRNAs (miRNAs), involved in different signaling pathways of SSc pathogenesis. The expression of key components in transforming growth factor-beta (TGF-beta) signaling pathway has been found to be regulated by miRNAs both upstream and downstream of TGF beta. We are specifically interested in the pathway components upstream of TGF beta, while miRNAs in other signaling pathways have not been extensively studied. The emerging role of miRNAs in vasculopathy of SSc suggests a promising new direction for future investigation. Elucidation of the regulatory role of miRNAs in the expression of signaling factors may facilitate the discovery of novel biomarkers in SSc and improve the understanding and treatment of this disease. PMID- 26365210 TI - Lifitegrast Ophthalmic Solution 5.0% versus Placebo for Treatment of Dry Eye Disease: Results of the Randomized Phase III OPUS-2 Study. AB - PURPOSE: Lifitegrast is an integrin antagonist that decreases T-cell-mediated inflammation associated with dry eye disease (DED). We report the results of OPUS 2, a phase III study evaluating the efficacy and safety of lifitegrast compared with placebo for the treatment of DED. DESIGN: A 12-week, multicenter, randomized, prospective, double-masked, placebo-controlled clinical trial. PARTICIPANTS: Adults aged >=18 years with use of artificial tears within 30 days, inferior corneal staining score >=0.5 (0-4 scale), Schirmer tear test (without anesthesia) >=1 and <=10 mm, and eye dryness score >=40 (0-100 visual analogue scale [VAS]). METHODS: Subjects were randomized 1:1 after 14-day placebo run-in to lifitegrast ophthalmic solution 5.0% or placebo twice daily for 84 days. MAIN OUTCOME MEASURES: Co-primary efficacy end points were change, from baseline to day 84, in eye dryness score (VAS, both eyes) and inferior corneal fluorescein staining score in the designated study eye. Secondary end points were change, from baseline to day 84, in ocular discomfort score (0-4 scale) in study eye, eye discomfort score (VAS), total corneal staining score in the study eye, and nasal conjunctival lissamine green staining score (0-4 scale) in the study eye. Treatment-emergent adverse events (TEAEs) were recorded. RESULTS: A total of 718 subjects were randomized: placebo, n = 360; lifitegrast, n = 358 (intent-to-treat population). Lifitegrast-treated subjects experienced greater improvement in eye dryness than placebo-treated subjects (treatment effect, 12.61; 95% confidence interval [CI], 8.51-16.70; P < 0.0001). There was no between-group difference in inferior corneal staining (treatment effect, 0.03; 95% CI, -0.10 to 0.17; P = 0.6186). There was nominally significant improvement of secondary symptom end points among lifitegrast-treated subjects: ocular discomfort (nominal P = 0.0005) and eye discomfort (nominal, P < 0.0001). There were no between-group differences on secondary signs: total corneal staining and nasal lissamine staining. More lifitegrast-treated subjects (33.7%) than placebo-treated subjects (16.4%) experienced ocular TEAEs; no ocular TEAEs were serious. CONCLUSIONS: Lifitegrast met the co-primary symptom end point (eye dryness) but not the co-primary sign end point (inferior corneal staining). Secondary end point findings were consistent with this pattern. Most ocular TEAEs were mild to moderate; there were no unexpected TEAEs. Lifitegrast warrants further consideration as a treatment for DED. PMID- 26365211 TI - In situ growth of carbon nanotubes on Ni/MgO: a facile preparation of efficient catalysts for the production of synthetic natural gas from syngas. AB - Ni/MgO-CNTs catalysts are prepared by in situ chemical vapor deposition growth of CNTs on Ni/MgO. These catalysts exhibit an improved performance for the production of synthetic natural gas from syngas, which is attributed to the formation of highly catalytic active interfaces among Ni, CNTs and MgO. PMID- 26365213 TI - Flexible Tuning of Unsaturated beta-Substituents on Zn Porphyrins: A Synthetic, Spectroscopic and Computational Study. AB - A series of zinc porphyrins substituted at adjacent beta-positions with a CN group and para-substituted ethenyl/ethynyl-phenyl group have been studied using electronic absorption spectroscopy, resonance Raman spectroscopy and DFT calculations. The oxidative nucleophilic substitution of hydrogen was utilized for the introduction of a cyano substituent on the porphyrin ring. This modification has a remarkable electronic effect on the ring. The resulting porphyrin cyanoaldehyde was further modified in Wittig condensations to give series of arylalkene- and arylalkyne-substituted derivatives. This substitution pattern caused significant redshifting and broadening of the B band, tuning from 433-446 nm. Additionally the Q/B band intensity ratios show much higher values than observed for the parent porphyrin ZnTPP (0.20 vs. 0.03). Careful analysis of the electronic transitions using DFT and resonance Raman spectroscopy reveal that the substituent does not significantly perturb the electronic structure of the porphyrin core, which is still well described by Gouterman's four-orbital model. However, the substituents do play a role in elongating the conjugation length and this results in the observed spectral changes. PMID- 26365212 TI - A phase II study of decitabine and gemtuzumab ozogamicin in newly diagnosed and relapsed acute myeloid leukemia and high-risk myelodysplastic syndrome. AB - Decitabine may open the chromatin structure of leukemia cells making them accessible to the calicheamicin epitope of gemtuzumab ozogamicin (GO). A total of 110 patients (median age 70 years; range 27-89 years) were treated with decitabine and GO in a trial designed on model-based futility to accommodate subject heterogeneity: group 1: relapsed/refractory acute myeloid leukemia (AML) with complete remission duration (CRD) <1 year (N=28, 25%); group 2: relapsed/refractory AML with CRD ?1 year (N=5, 5%); group 3: untreated AML unfit for intensive chemotherapy or untreated myelodysplastic syndrome (MDS) or untreated myelofibrosis (MF; N=57, 52%); and group 4: AML evolving from MDS or relapsed/refractory MDS or MF (N=20, 18%). Treatment consisted of decitabine 20 mg/m(2) daily for 5 days and GO 3 mg/m(2) on day 5. Post-induction therapy included five cycles of decitabine+GO followed by decitabine alone. Complete remission (CR)/CR with incomplete count recovery was achieved in 39 (35%) patients; group 1= 5/28 (17%), group 2=3/5 (60%), group 3=24/57 (42%) and group 4=7/20 (35%). The 8-week mortality in groups 3 and 4 was 16% and 10%, respectively. Common drug-related adverse events included nausea, mucositis and hemorrhage. Decitabine and GO improved the response rate but not overall survival compared with historical outcomes in untreated AML ?60 years. PMID- 26365214 TI - Is cell culture a risky business? Risk analysis based on scientist survey data. AB - Cell culture is a technique that requires vigilance from the researcher. Common cell culture problems, including contamination with microorganisms or cells from other cultures, can place the reliability and reproducibility of cell culture work at risk. Here we use survey data, contributed by research scientists based in Australia and New Zealand, to assess common cell culture risks and how these risks are managed in practice. Respondents show that sharing of cell lines between laboratories continues to be widespread. Arrangements for mycoplasma and authentication testing are increasingly in place, although scientists are often uncertain how to perform authentication testing. Additional risks are identified for preparation of frozen stocks, storage and shipping. PMID- 26365216 TI - Major bleeding in hemodialysis patients using unfractionated or low molecular weight heparin: a single-center study. AB - BACKGROUND: Successful hemodialysis (HD) requires circuit anticoagulation, with either unfractionated heparin (UFH) or low molecular weight heparin (LMWH) - it is not clear if differences in risk or benefit between these agents exist. We report our experience of major bleeding in patients on hemodialysis receiving either LMWH or UFH for anticoagulation of the dialysis circuit. We also examined any effect of anti-platelet agents or oral anticoagulants on bleeding rates. METHODS: An observational, retrospective, single-center study. Bleeding episodes are described using the International Society of Thrombosis and Hemostasis (ISTH) definition of a major bleeding event, and by extending this group to include all bleeds that led to a hospital admission (clinically significant). Incident event rates are reported per 100 at risk patient years, and event-free survival calculated using multivariate analysis by Cox-proportional hazard ratio. RESULTS: We report on 522 patients (792 years of exposure) in the UFHHD cohort and 889 patients (1,200 years of exposure) in the LMWH-HD cohort. The incidence of a major bleed was 1.33%, and 1.92% bleeds respectively. The incidences of clinically significant bleeding rates were 3.33% and 3.96% respectively. There was no significant difference in bleed free survival between UFH compared to LMWH (OR 0.904, CI 0.557 a?? 1.468, p = 0.684). Warfarin or anti-platelet usage did not increase the risk of bleeding when comparing patients not on any anticoagulants. CONCLUSIONS: There is no difference in bleeding rates between hemodialysis patients treated with either UFH or LMWH for anticoagulation of the extracorporeal circuit. We believe that both heparins have similar safety profiles when used for extracorporeal anticoagulation and that bleeding risk should not determine the choice of anticoagulation. PMID- 26365215 TI - Length of urban residence and obesity among within-country rural-to-urban Andean migrants. AB - OBJECTIVE: To evaluate the association between length of residence in an urban area and obesity among Peruvian rural-to-urban migrants. DESIGN: Cross-sectional database analysis of the migrant group from the PERU MIGRANT Study (2007). Exposure was length of urban residence, analysed as both a continuous (10-year units) and a categorical variable. Four skinfold site measurements (biceps, triceps, subscapular and suprailiac) were used to calculate body fat percentage and obesity (body fat percentage >25% males, >33% females). We used Poisson generalized linear models to estimate adjusted prevalence ratios and 95 % confidence intervals. Multicollinearity between age and length of urban residence was assessed using conditional numbers and correlation tests. SETTING: A peri urban shantytown in the south of Lima, Peru. SUBJECTS: Rural-to-urban migrants (n 526) living in Lima. RESULTS: Multivariable analyses showed that for each 10-year unit increase in residence in an urban area, rural-to-urban migrants had, on average, a 12 % (95 % CI 6, 18 %) higher prevalence of obesity. This association was also present when length of urban residence was analysed in categories. Sensitivity analyses, conducted with non-migrant groups, showed no evidence of an association between 10-year age units and obesity in rural (P=0.159) or urban populations (P=0.078). High correlation and a large conditional number between age and length of urban residence were found, suggesting a strong collinearity between both variables. CONCLUSIONS: Longer lengths of urban residence are related to increased obesity in rural-to-urban migrant populations; therefore, interventions to prevent obesity in urban areas may benefit from targeting migrant groups. PMID- 26365217 TI - Peritonitis in children with automated peritoneal dialysis. AB - This is a retrospective study including 36 Saudi children who were on automated peritoneal dialysis (APD) at the Al-Hada Armed Forces Hospital, Taif, Kingdom of Saudi Arabia during seven years. A total of 10 boys and 26 girls with end-stage renal disease (ESRD) received APD for a total of 731.75 months. 36 episodes of peritonitis occurred in 17 children (47%). The frequency of peritonitis was one episode per 20.3 treatment months. Catheters were changed in 3 patients (8%). Three patients were switched to chronic hemodialysis, while 4 underwent successful renal transplantation. Results revealed that 11 patients (19%) were culturenegative, while 25 (81%) were culturepositive. Gram-positive organisms were responsible for the majority of peritonitis episodes (50%) followed by Gram negative organisms (31%); occurrence was more frequent in young patients. Empiric antibiotic therapy covered both gram-positive and gram-negative organisms. However, all gram-positive isolated microorganisms showed sensitivity to vancomycin. On the other hand, most gram-negative organisms showed sensitivity to ceftazidime or tobramycin. PMID- 26365218 TI - Contingent versus routine third-trimester screening for late fetal growth restriction. AB - OBJECTIVE: To evaluate the use of third-trimester ultrasound screening for late fetal growth restriction (FGR) on a contingent basis, according to risk accrued in the second trimester, in an unselected population. METHODS: Maternal characteristics, fetal biometry and second-trimester uterine artery (UtA) Doppler were included in logistic regression analysis to estimate risk for late FGR (birth weight < 3(rd) percentile, or 3(rd) -10(th) percentile plus abnormal cerebroplacental ratio or UtA Doppler, with delivery >= 34 weeks). Based on the second-trimester risk, strategies for performing contingent third-trimester ultrasound examinations in 10%, 25% or 50% of the cohort were tested against a strategy of routine ultrasound scanning in the entire population at 32 + 0 to 33 + 6 weeks. RESULTS: Models were constructed based on 1393 patients and validated in 1303 patients, including 73 (5.2%) and 82 late FGR (6.3%) cases, respectively. At the second-trimester scan, the a-posteriori second-trimester risk (a posteriori first-trimester risk (baseline a-priori risk and mean arterial blood pressure) combined with second-trimester abdominal circumference and UtA Doppler) yielded an area under the receiver-operating characteristics curve (AUC) of 0.81 (95% CI, 0.74-0.87) (detection rate (DR), 43.1% for a 10% false-positive rate (FPR)). The combination of a-posteriori second-trimester risk plus third trimester estimated fetal weight (full model) yielded an AUC of 0.92 (95% CI, 0.88-0.96) (DR, 74% for a 10% FPR). Subjecting 10%, 25% or 50% of the study population to third-trimester ultrasound, based on a-posteriori second-trimester risk, gave AUCs of 0.81 (95% CI, 0.75-0.88), 0.84 (95% CI, 0.78-0.91) and 0.89 (95% CI, 0.84-0.94), respectively. Only the 50% contingent model proved statistically equivalent to performing routine third-trimester ultrasound scans (AUC, 0.92 (95% CI, 0.88-0.96), P = 0.11). CONCLUSION: A strategy of selecting 50% of the study population to undergo third-trimester ultrasound examination, based on accrued risk in the second trimester, proved equivalent to routine third trimester ultrasound scanning in predicting late FGR. PMID- 26365219 TI - Environmental cost of using poor decision metrics to prioritize environmental projects. AB - Conservation decision makers commonly use project-scoring metrics that are inconsistent with theory on optimal ranking of projects. As a result, there may often be a loss of environmental benefits. We estimated the magnitudes of these losses for various metrics that deviate from theory in ways that are common in practice. These metrics included cases where relevant variables were omitted from the benefits metric, project costs were omitted, and benefits were calculated using a faulty functional form. We estimated distributions of parameters from 129 environmental projects from Australia, New Zealand, and Italy for which detailed analyses had been completed previously. The cost of using poor prioritization metrics (in terms of lost environmental values) was often high--up to 80% in the scenarios we examined. The cost in percentage terms was greater when the budget was smaller. The most costly errors were omitting information about environmental values (up to 31% loss of environmental values), omitting project costs (up to 35% loss), omitting the effectiveness of management actions (up to 9% loss), and using a weighted-additive decision metric for variables that should be multiplied (up to 23% loss). The latter 3 are errors that occur commonly in real-world decision metrics, in combination often reducing potential benefits from conservation investments by 30-50%. Uncertainty about parameter values also reduced the benefits from investments in conservation projects but often not by as much as faulty prioritization metrics. PMID- 26365220 TI - The effects of fibroblast growth factor-2 and pluripotent astrocytic stem cells on cognitive function in a rat model of neonatal hypoxic-ischemic brain injury. AB - OBJECTIVE: This study aimed to determine the effect of pluripotent astrocytic stem cells (PASCs) and fibroblast growth factor-2 (FGF-2) on cognitive function in neonatal rats with hypoxic-ischemic brain injury (HIBI). METHODS: The study was performed on 7-d-old rats that were randomly divided into four groups. All rats, except those in the sham group, were kept in a hypoxic chamber containing 8% oxygen for 2 h after the ligation of the right carotid artery. Next, 5 d after HIBI was induced, PASCs were administered to the motor cortex, and FGF-2 was administered intraperitoneally to group AF; PASCs were administered to the motor cortex, and salt solution buffered with phosphate was administered intraperitoneally to group A; and fresh cell culture solution (medium) was administered to group M. Immunofluorescence was used to localize the administered PASCs in the brains of rats from groups A and AF. The Morris water maze tank (MWM) test was performed to assess the rats' cognitive functions at week 12. The rats that were administered PASCs were observed for the development of neoplasms and autopsies were performed after 30 months. RESULTS: PASCs migrated to damaged brain regions surrounding the hippocampus in groups A and AF. The mean platform finding time (PFT) significantly decreased over time in each group on day 1-4 of MWM testing (p < 0.001). On day 2-4, the mean PFT was shortest in group S followed by group AF. In group A, the PFT was significantly longer than in group S on day 3-4 (p = 0.01 and 0.007, respectively). On day 5 of the MWM test, the time spent in the eastern quadrant (which previously contained the platform) was longest in group S followed by groups AF, A, and M; however, the differences between groups were not significant (p = 0.51). After 30 months, none of the rats in groups A or AF had benign or malignant neoplasms. CONCLUSIONS: Following the administration of PASCs in rats with experimentally induced HIBI, PASCs migrated to the injured brain regions; however, treatment with PASCs did not have a positive effect on cognitive function. The administration of FGF-2 together with PASCs resulted in positive cognitive results, although not at the level of significance. PMID- 26365222 TI - A glimpse at long regulatory RNAs in various organisms. PMID- 26365221 TI - Seasonality of avian influenza A(H7N9) activity and risk of human A(H7N9) infections from live poultry markets. PMID- 26365223 TI - Understanding stress in the healthy animal - potential paths for progress. AB - Although stress is usually associated with disease, the physiological and behavioral responses to stressors are critical mechanisms of resilience for healthy organisms. A recent workshop comprised of researchers who study healthy humans and both free-living and captive non-human animals identified a number of key roadblocks that are impeding progress in understanding how stress responses integrate into the normal physiology of an animal. These include the lack of: (1) an unambiguous definition of a stress phenotype; (2) a robust biomarker, or suite of biomarkers, to indicate that phenotype; (3) theoretical and quantitative models to predict how humans and other animals will react to stressors; (4) a comprehensive understanding of how individual variability in stress responses arise and (5) an understanding of the transitions between acute and chronic stress responses. Collectively, these deficiencies impair our ability to both assess the physiological status of individuals and develop procedures and techniques to reverse the effects elicited by chronic stress before they become pathological. Workshop participants also identified a number of potential approaches to facilitate progress on these problems. They include: (1) increased use of mathematical models to provide quantitative predictions; (2) use of network theory to expose emergent properties not predicted from traditional approaches; (3) development and deployment of improved sensor technology that will allow long-term, dynamic, non-invasive, multi-factor measurements of suites of stress mediators and (4) the recruitment of scientists with diverse skill sets, such as engineers, bioinformaticians, etc.; and (5) the training of young scientists in the multidisciplinary study of stress. Incorporating these approaches in new research should reinvigorate the study of stress and stimulate progress in understanding both how healthy humans cope with stressors and how other animals, including free-living animals, cope with stressors in a rapidly changing environment. PMID- 26365224 TI - Antimicrobials therapy of anaerobic infections. AB - Anaerobes predominant in the normal human skin and mucous membranes bacterial flora are often a cause of endogenous infections. Anaerobic bacteria are difficult to isolate from infectious sites, and are often overlooked. Anaerobic infections caused by anaerobes can occur in all body sites, including the central nervous system (CNS), oral cavity, head and neck, chest, abdomen, pelvis, skin and soft tissues. The treatment of these infections is complicated by the slow growth of these organisms, their polymicrobial nature and the growing resistance of anaerobes to antimicrobials agents. Antimicrobials are frequently the only form of therapy needed, but in others, they are an important adjunct to surgical drainage and correction of pathology. Because anaerobes are often recovered with aerobic and facultative bacteria, the chosen antimicrobials should cover all pathogens. The antimicrobials effective against anaerobic organisms are metronidazole, carbapenems, combinations of a beta-lactam and a beta-lactamase inhibitor, chloramphenicol, tigecycline and clindamycin. PMID- 26365225 TI - Reply: To PMID 26361825. PMID- 26365226 TI - Rapid detection of Bombyx mori nucleopolyhedrovirus (BmNPV) by loop-mediated isothermal amplification assay combined with a lateral flow dipstick method. AB - The Bombyx mori nucleopolyhedrovirus (BmNPV) is a principal pathogen of the domestic silkworm. The disease often breaks out in sericultural countries and due to its high infectivity; it is difficult to control, resulting in heavy economic loss. In order to develop a rapid, sensitive visual detection and simple-to-use novel technology for detection of BmNPV, a loop-mediated isothermal amplification (LAMP) assay combined with a lateral flow dipstick (LFD) method was described. In this study, a set of four primers and a labeled probe were designed specifically to recognize six distinct regions of the BmNPV gp41 gene, and the LAMP for the detection of BmNPV was developed by isothermal amplification at 61 degrees C for 45 min, followed by hybridization with an FITC-labeled DNA probe for 5 min and detected by LFD within 5 min. The detection limit of LAMP-LFD was 0.2 pg DNA extracted from silkworm infected with BmNPV and was 100 times more sensitive than conventional PCR. No product was generated from silkworm infected with other viruses. Furthermore, we applied the technique to detect BmNPV in the hemolymph and feces at different intervals post infection (pi). In conclusion, the novel LAMP-LFD setup presented here is simple, rapid, reliable, and has the potential for future use in the detection of BmNPV. PMID- 26365227 TI - Practical and low cost whole-organism motility assay: A step-by-step protocol. AB - Here, we provide a step-by-step protocol for a practical and low cost whole organism assay for the screening of chemical compounds for activity against parasitic worms. This assay has considerable advantages over conventional methods, mainly in relation to ease of use, throughput, time and cost. It is readily suited to the screening of hundreds to thousands of compounds for subsequent hit-to-lead optimisation, and should be applicable to many different parasites and other organisms commensurate with the size of wells in the microtiter plates used for phenotypic screening. PMID- 26365228 TI - Real-time reverse transcriptase polymerase chain reaction assays for Middle East Respiratory Syndrome. AB - Here we designed and tested two highly specific quantitative TaqMan((r))-MGB based reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) assays for Middle East Respiratory Syndrome (MERS). The primers and probes for these assays were evaluated and found to have a limit of detection (LOD) of 0.005 plaque-forming units/PCR (pfu/PCR). PMID- 26365229 TI - Genetic diversity in cytochrome c oxidase I gene of Anopheles mosquitoes. AB - Genetic diversity in cytochrome c oxidase I (coxI) among 7 species of Anopheles mosquitoes from Pakistan, and 37 species from different geographical regions of the world, was recorded. Automatic Barcode Gap Discovery (ABGD) analysis revealed a clear gap between intraspecific and interspecific distances of 7 species from Pakistan. However, genetic distances of 37 Anopheles species failed to adequately differentiate species in a global context. Intraspecific and interspecific divergences for 7 Anopheles species of Pakistan varied from 0.0% to 2.5% (mean = 0.49%) and 8% to 22.3% (mean = 12.77%), respectively. Similarly, intraspecific distances for 37 species from different parts of world ranged from 0.0% to 11.2% (mean = 0.65%) while values of interspecific divergences ranged from 3.4% to 35% (mean = 11.75%). Although phylogenetic tree revealed separate clades for 7 Anopheles species of Pakistan, it failed to produce separate clades for 37 species of the world. It is concluded that although standard barcode region is helpful for identifying Anopheles mosquitoes, combination of multi-locus approaches and morphology may be required to accurately identify species in this genus. PMID- 26365230 TI - Validation and clinical application of a molecular method for the identification of Cryptococcus neoformans/Cryptococcus gattii complex DNA in human clinical specimens. AB - The diagnosis of cryptococcosis is usually performed based on cultures of tissue or body fluids and isolation of the fungus, but this method may require several days. Direct microscopic examination, although rapid, is relatively insensitive. Biochemical and immunodiagnostic rapid tests are also used. However, all of these methods have limitations that may hinder final diagnosis. The increasing incidence of fungal infections has focused attention on tools for rapid and accurate diagnosis using molecular biological techniques. Currently, PCR-based methods, particularly nested, multiplex and real-time PCR, provide both high sensitivity and specificity. In the present study, we evaluated a nested PCR targeting the gene encoding the ITS-1 and ITS-2 regions of rDNA in samples from a cohort of patients diagnosed with cryptococcosis. The results showed that in our hands, this Cryptococcus nested PCR assay has 100% specificity and 100% sensitivity and was able to detect until 2 femtograms of Cryptococcus DNA. PMID- 26365231 TI - Artificial photosynthesis for production of hydrogen peroxide and its fuel cells. AB - The reducing power released from photosystem I (PSI) via ferredoxin enables the reduction of NADP(+) to NADPH, which is essential in the Calvin-Benson cycle to make sugars in photosynthesis. Alternatively, PSI can reduce O2 to produce hydrogen peroxide as a fuel. This article describes the artificial version of the photocatalytic production of hydrogen peroxide from water and O2 using solar energy. Hydrogen peroxide is used as a fuel in hydrogen peroxide fuel cells to make electricity. The combination of the photocatalytic H2O2 production from water and O2 using solar energy with one-compartment H2O2 fuel cells provides on site production and usage of H2O2 as a more useful and promising solar fuel than hydrogen. This article is part of a Special Issue entitled Biodesign for Bioenergetics--The design and engineering of electronc transfer cofactors, proteins and protein networks, edited by Ronald L. Koder and J.L. Ross Anderson. PMID- 26365232 TI - Genomics in early infantile epileptic encephalopathies - trials and tribulations. PMID- 26365233 TI - Investigating the validity and usability of an interactive computer programme for assessing competence in telephone-based mental health triage. AB - Telephone-based mental health triage services are frontline health-care providers that operate 24/7 to facilitate access to psychiatric assessment and intervention for people requiring assistance with a mental health problem. The mental health triage clinical role is complex, and the populations triage serves are typically high risk; yet to date, no evidence-based methods have been available to assess clinician competence to practice telephone-based mental health triage. The present study reports the findings of a study that investigated the validity and usability of the Mental Health Triage Competency Assessment Tool, an evidence based, interactive computer programme designed to assist clinicians in developing and assessing competence to practice telephone-based mental health triage. PMID- 26365234 TI - A computational method for studying the relation between alternative splicing and DNA methylation. AB - Alternative splicing is an important mechanism in eukaryotes that expands the transcriptome and proteome significantly. It plays an important role in a number of biological processes. Understanding its regulation is hence an important challenge. Recently, increasing evidence has been collected that supports an involvement of intragenic DNA methylation in the regulation of alternative splicing. The exact mechanisms of regulation, however, are largely unknown, and speculated to be complex: different methylation profiles might exist, each of which could be associated with a different regulation mechanism. We present a computational technique that is able to determine such stable methylation patterns and allows to correlate these patterns with inclusion propensity of exons. Pattern detection is based on dynamic time warping (DTW) of methylation profiles, a sophisticated similarity measure for signals that can be non trivially transformed. We design a flexible self-organizing map approach to pattern grouping. Exemplary application on available data sets indicates that stable patterns which correlate non-trivially with exon inclusion do indeed exist. To improve the reliability of these predictions, further studies on larger data sets will be required. We have thus taken great care that our software runs efficiently on modern hardware, so that it can support future studies on large scale data sets. PMID- 26365235 TI - Sizing femtogram amounts of dsDNA by single-molecule counting. AB - Modern molecular-biology applications raise renewed interest in sizing minute amounts of DNA. In this work we utilize single-molecule imaging with in situ size calibration to accurately analyze the size and mass distribution of DNA samples. We exploit the correlation between DNA length and its fluorescence intensity after staining in order to assess the length of individual DNA fragments by fluorescence microscopy. Synthetic reference DNA standards are added to the investigated sample before staining and serve as internal size calibrators, supporting a robust assay for accurate DNA sizing. Our results demonstrate the ability to reconstruct the exact length distribution in a complex DNA sample by sizing a subset containing only femtogram amounts of DNA, thus, outperforming microfluidic gel electrophoresis which is the currently accepted gold standard. This assay may find useful applications for genetic analysis where the exact size distribution of DNA molecules is critical and the availability of genetic material is limited. PMID- 26365236 TI - A ruthenium dimer complex with a flexible linker slowly threads between DNA bases in two distinct steps. AB - Several multi-component DNA intercalating small molecules have been designed around ruthenium-based intercalating monomers to optimize DNA binding properties for therapeutic use. Here we probe the DNA binding ligand [MU C4(cpdppz)2(phen)4Ru2](4+), which consists of two Ru(phen)2dppz(2+) moieties joined by a flexible linker. To quantify ligand binding, double-stranded DNA is stretched with optical tweezers and exposed to ligand under constant applied force. In contrast to other bis-intercalators, we find that ligand association is described by a two-step process, which consists of fast bimolecular intercalation of the first dppz moiety followed by ~10-fold slower intercalation of the second dppz moiety. The second step is rate-limited by the requirement for a DNA-ligand conformational change that allows the flexible linker to pass through the DNA duplex. Based on our measured force-dependent binding rates and ligand-induced DNA elongation measurements, we are able to map out the energy landscape and structural dynamics for both ligand binding steps. In addition, we find that at zero force the overall binding process involves fast association (~10 s), slow dissociation (~300 s), and very high affinity (Kd ~10 nM). The methodology developed in this work will be useful for studying the mechanism of DNA binding by other multi-step intercalating ligands and proteins. PMID- 26365237 TI - ASD v3.0: unraveling allosteric regulation with structural mechanisms and biological networks. AB - Allosteric regulation, the most direct and efficient way of regulating protein function, is induced by the binding of a ligand at one site that is topographically distinct from an orthosteric site. Allosteric Database (ASD, available online at http://mdl.shsmu.edu.cn/ASD) has been developed to provide comprehensive information featuring allosteric regulation. With increasing data, fundamental questions pertaining to allostery are currently receiving more attention from the mechanism of allosteric changes in an individual protein to the entire effect of the changes in the interconnected network in the cell. Thus, the following novel features were added to this updated version: (i) structural mechanisms of more than 1600 allosteric actions were elucidated by a comparison of site structures before and after the binding of an modulator; (ii) 261 allosteric networks were identified to unveil how the allosteric action in a single protein would propagate to affect downstream proteins; (iii) two of the largest human allosteromes, protein kinases and GPCRs, were thoroughly constructed; and (iv) web interface and data organization were completely redesigned for efficient access. In addition, allosteric data have largely expanded in this update. These updates are useful for facilitating the investigation of allosteric mechanisms, dynamic networks and drug discoveries. PMID- 26365238 TI - MCM ring hexamerization is a prerequisite for DNA-binding. AB - The hexameric Minichromosome Maintenance (MCM) protein complex forms a ring that unwinds DNA at the replication fork in eukaryotes and archaea. Our recent crystal structure of an archaeal MCM N-terminal domain bound to single-stranded DNA (ssDNA) revealed ssDNA associating across tight subunit interfaces but not at the loose interfaces, indicating that DNA-binding is governed not only by the DNA binding residues of the subunits (MCM ssDNA-binding motif, MSSB) but also by the relative orientation of the subunits. We now extend these findings by showing that DNA-binding by the MCM N-terminal domain of the archaeal organism Pyrococcus furiosus occurs specifically in the hexameric oligomeric form. We show that mutants defective for hexamerization are defective in binding ssDNA despite retaining all the residues observed to interact with ssDNA in the crystal structure. One mutation that exhibits severely defective hexamerization and ssDNA binding is at a conserved phenylalanine that aligns with the mouse Mcm4(Chaos3) mutation associated with chromosomal instability, cancer, and decreased intersubunit association. PMID- 26365239 TI - Adapting capillary gel electrophoresis as a sensitive, high-throughput method to accelerate characterization of nucleic acid metabolic enzymes. AB - Detailed biochemical characterization of nucleic acid enzymes is fundamental to understanding nucleic acid metabolism, genome replication and repair. We report the development of a rapid, high-throughput fluorescence capillary gel electrophoresis method as an alternative to traditional polyacrylamide gel electrophoresis to characterize nucleic acid metabolic enzymes. The principles of assay design described here can be applied to nearly any enzyme system that acts on a fluorescently labeled oligonucleotide substrate. Herein, we describe several assays using this core capillary gel electrophoresis methodology to accelerate study of nucleic acid enzymes. First, assays were designed to examine DNA polymerase activities including nucleotide incorporation kinetics, strand displacement synthesis and 3'-5' exonuclease activity. Next, DNA repair activities of DNA ligase, flap endonuclease and RNase H2 were monitored. In addition, a multicolor assay that uses four different fluorescently labeled substrates in a single reaction was implemented to characterize GAN nuclease specificity. Finally, a dual-color fluorescence assay to monitor coupled enzyme reactions during Okazaki fragment maturation is described. These assays serve as a template to guide further technical development for enzyme characterization or nucleoside and non-nucleoside inhibitor screening in a high-throughput manner. PMID- 26365240 TI - Redesign of the monomer-monomer interface of Cre recombinase yields an obligate heterotetrameric complex. AB - Cre recombinase catalyzes the cleavage and religation of DNA at loxP sites. The enzyme is a homotetramer in its functional state, and the symmetry of the protein complex enforces a pseudo-palindromic symmetry upon the loxP sequence. The Cre lox system is a powerful tool for many researchers. However, broader application of the system is limited by the fixed sequence preferences of Cre, which are determined by both the direct DNA contacts and the homotetrameric arrangement of the Cre monomers. As a first step toward achieving recombination at arbitrary asymmetric target sites, we have broken the symmetry of the Cre tetramer assembly. Using a combination of computational and rational protein design, we have engineered an alternative interface between Cre monomers that is functional yet incompatible with the wild-type interface. Wild-type and engineered interface halves can be mixed to create two distinct Cre mutants, neither of which are functional in isolation, but which can form an active heterotetramer when combined. When these distinct mutants possess different DNA specificities, control over complex assembly directly discourages recombination at unwanted half site combinations, enhancing the specificity of asymmetric site recombination. The engineered Cre mutants exhibit this assembly pattern in a variety of contexts, including mammalian cells. PMID- 26365241 TI - A high-throughput assay for the comprehensive profiling of DNA ligase fidelity. AB - DNA ligases have broad application in molecular biology, from traditional cloning methods to modern synthetic biology and molecular diagnostics protocols. Ligation based detection of polynucleotide sequences can be achieved by the ligation of probe oligonucleotides when annealed to a complementary target sequence. In order to achieve a high sensitivity and low background, the ligase must efficiently join correctly base-paired substrates, while discriminating against the ligation of substrates containing even one mismatched base pair. In the current study, we report the use of capillary electrophoresis to rapidly generate mismatch fidelity profiles that interrogate all 256 possible base-pair combinations at a ligation junction in a single experiment. Rapid screening of ligase fidelity in a 96-well plate format has allowed the study of ligase fidelity in unprecedented depth. As an example of this new method, herein we report the ligation fidelity of Thermus thermophilus DNA ligase at a range of temperatures, buffer pH and monovalent cation strength. This screen allows the selection of reaction conditions that maximize fidelity without sacrificing activity, while generating a profile of specific mismatches that ligate detectably under each set of conditions. PMID- 26365243 TI - Accurate transcriptome-wide prediction of microRNA targets and small interfering RNA off-targets with MIRZA-G. PMID- 26365242 TI - The reverse transcription signature of N-1-methyladenosine in RNA-Seq is sequence dependent. AB - The combination of Reverse Transcription (RT) and high-throughput sequencing has emerged as a powerful combination to detect modified nucleotides in RNA via analysis of either abortive RT-products or of the incorporation of mismatched dNTPs into cDNA. Here we simultaneously analyze both parameters in detail with respect to the occurrence of N-1-methyladenosine (m(1)A) in the template RNA. This naturally occurring modification is associated with structural effects, but it is also known as a mediator of antibiotic resistance in ribosomal RNA. In structural probing experiments with dimethylsulfate, m(1)A is routinely detected by RT-arrest. A specifically developed RNA-Seq protocol was tailored to the simultaneous analysis of RT-arrest and misincorporation patterns. By application to a variety of native and synthetic RNA preparations, we found a characteristic signature of m(1)A, which, in addition to an arrest rate, features misincorporation as a significant component. Detailed analysis suggests that the signature depends on RNA structure and on the nature of the nucleotide 3' of m(1)A in the template RNA, meaning it is sequence dependent. The RT-signature of m(1)A was used for inspection and confirmation of suspected modification sites and resulted in the identification of hitherto unknown m(1)A residues in trypanosomal tRNA. PMID- 26365244 TI - RlmCD-mediated U747 methylation promotes efficient G748 methylation by methyltransferase RlmAII in 23S rRNA in Streptococcus pneumoniae; interplay between two rRNA methylations responsible for telithromycin susceptibility. AB - Adenine at position 752 in a loop of helix 35 from positions 745 to 752 in domain II of 23S rRNA is involved in binding to the ribosome of telithromycin (TEL), a member of ketolides. Methylation of guanine at position 748 by the intrinsic methyltransferase RlmA(II) enhances binding of telithromycin (TEL) to A752 in Streptococcus pneumoniae. We have found that another intrinsic methylation of the adjacent uridine at position 747 enhances G748 methylation by RlmA(II), rendering TEL susceptibility. U747 and another nucleotide, U1939, were methylated by the dual-specific methyltransferase RlmCD encoded by SP_1029 in S. pneumoniae. Inactivation of RlmCD reduced N1-methylated level of G748 by RlmA(II) in vivo, leading to TEL resistance when the nucleotide A2058, located in domain V of 23S rRNA, was dimethylated by the dimethyltransferase Erm(B). In vitro methylation of rRNA showed that RlmA(II) activity was significantly enhanced by RlmCD-mediated pre-methylation of 23S rRNA. These results suggest that RlmCD-mediated U747 methylation promotes efficient G748 methylation by RlmA(II), thereby facilitating TEL binding to the ribosome. PMID- 26365246 TI - Salt-kneading: alternative sizing of active pharmaceutical ingredients? AB - The most of currently produced active pharmaceutical ingredients (APIs) are poorly soluble in the human body. One of the options how to increase their dissolution rate is reducing their particle size. If very small particles of API are desired, traditional milling methods often cause smeared, agglomerated or non flowing particles due to the forces applied. We tried to compare some of milling methods with the salt-kneading method, which is not typically used in the pharmaceutical industry. Salt-kneading process is driven by several variable parameters (e.g. the amount, hardness and particle size of the salt-kneading material), which influence the degree of size reduction of API particles which are chafed by a surplus of salt-kneading material. A model poorly-soluble API was separately processed with oscillation mill, vibratory mill and kneader; and the morphology, size distribution and solid form of prepared particles were analyzed. Our basic variation of salt-kneading parameters showed the potential of the salt kneading method, which appears a very effective method of API controlled reduction. The final size can be modified according to the amount and properties of the salt-kneading material. The availability of such a method equips pharmaceutical scientists with a size-reduction method that provides very small, rounded and free-flowing particles of the poorly soluble API and reduces non preferred needle shape. PMID- 26365245 TI - Probing binding hot spots at protein-RNA recognition sites. AB - We use evolutionary conservation derived from structure alignment of polypeptide sequences along with structural and physicochemical attributes of protein-RNA interfaces to probe the binding hot spots at protein-RNA recognition sites. We find that the degree of conservation varies across the RNA binding proteins; some evolve rapidly compared to others. Additionally, irrespective of the structural class of the complexes, residues at the RNA binding sites are evolutionary better conserved than those at the solvent exposed surfaces. For recognitions involving duplex RNA, residues interacting with the major groove are better conserved than those interacting with the minor groove. We identify multi-interface residues participating simultaneously in protein-protein and protein-RNA interfaces in complexes where more than one polypeptide is involved in RNA recognition, and show that they are better conserved compared to any other RNA binding residues. We find that the residues at water preservation site are better conserved than those at hydrated or at dehydrated sites. Finally, we develop a Random Forests model using structural and physicochemical attributes for predicting binding hot spots. The model accurately predicts 80% of the instances of experimental DeltaDeltaG values in a particular class, and provides a stepping-stone towards the engineering of protein-RNA recognition sites with desired affinity. PMID- 26365247 TI - Why may allopregnanolone help alleviate loneliness? AB - Impaired biosynthesis of Allopregnanolone (ALLO), a brain endogenous neurosteroid, has been associated with numerous behavioral dysfunctions, which range from anxiety- and depressive-like behaviors to aggressive behavior and changes in responses to contextual fear conditioning in rodent models of emotional dysfunction. Recent animal research also demonstrates a critical role of ALLO in social isolation. Although there are likely aspects of perceived social isolation that are uniquely human, there is also continuity across species. Both human and animal research show that perceived social isolation (which can be defined behaviorally in animals and humans) has detrimental effects on physical health, such as increased hypothalamic pituitary adrenal (HPA) activity, decreased brain-derived neurotrophic factor (BDNF) expression, and increased depressive behavior. The similarities between animal and human research suggest that perceived social isolation (loneliness) may also be associated with a reduction in the synthesis of ALLO, potentially by reducing BDNF regulation and increasing HPA activity through the hippocampus, amygdala, and bed nucleus of the stria terminalis (BNST), especially during social threat processing. Accordingly, exogenous administration of ALLO (or ALLO precursor, such as pregnenolone), in humans may help alleviate loneliness. Congruent with our hypothesis, exogenous administration of ALLO (or ALLO precursors) in humans has been shown to improve various stress-related disorders that show similarities between animals and humans i.e., post-traumatic stress disorders, traumatic brain injuries. Because a growing body of evidence demonstrates the benefits of ALLO in socially isolated animals, we believe our ALLO hypothesis can be applied to loneliness in humans, as well. PMID- 26365248 TI - Could a first-trimester blood phosphatidylethanol concentration ?4 nM be useful to identify women with moderate-to-heavy prenatal alcohol exposure who are at high risk of adverse pregnancy outcomes? AB - It is accepted that blood phosphatidylethanol (PEth) concentrations are reliable biomarkers of ethanol (alcohol) exposure. We therefore conducted a preliminary study to test the hypothesis that elevated blood PEth concentrations can help to identifying women with prenatal alcohol exposure who are at higher risk of adverse pregnancy outcomes. The study included 35 first-trimester pregnant women who self-reported alcohol ingestion and had PEth blood concentration ?4 nM at recruitment. As a control group, 233 first-trimester pregnant women who self reported as being either abstainers or light alcohol drinkers and had blood PEth concentrations <4 nM, were also included. All participants were followed up until completion of their pregnancies. Women with prenatal alcohol exposure and PEth concentrations ?4 nM had a risk ratio of spontaneous abortions of 3.21 (95%CI 0.93-11.06; P=0.074). Because of the potential implications in the prenatal care of women reporting risky alcohol exposure, the preliminary results from the present study indicate the need for testing the hypothesis in a more definitive approach. PMID- 26365249 TI - Revisiting the dystrophin-ATP connection: How half a century of research still implicates mitochondrial dysfunction in Duchenne Muscular Dystrophy aetiology. AB - Duchenne Muscular Dystrophy (DMD) is a fatal neuromuscular disease that is characterised by dystrophin-deficiency and chronic Ca(2+)-induced skeletal muscle wasting, which currently has no cure. DMD was once considered predominantly as a metabolic disease due to the myriad of metabolic insufficiencies evident in the musculature, however this aspect of the disease has been extensively ignored since the discovery of dystrophin. The collective historical and contemporary literature documenting these metabolic nuances has culminated in a series of studies that importantly demonstrate that metabolic dysfunction exists independent of dystrophin expression and a mild disease phenotype can be expressed even in the complete absence of dystrophin expression. Targeting and supporting metabolic pathways with anaplerotic and other energy-enhancing supplements has also shown therapeutic value. We explore the hypothesis that DMD is characterised by a systemic mitochondrial impairment that is central to disease aetiology rather than a secondary pathophysiological consequence of dystrophin-deficiency. PMID- 26365251 TI - Under-recognised co-morbidities in idiopathic pulmonary fibrosis: A review. AB - Co-morbidities in idiopathic pulmonary fibrosis are common. These co-morbidities include obstructive sleep apnoea, gastro-oesophageal reflux disease, pulmonary hypertension and depression. The presence of co-morbidities among patients with idiopathic pulmonary fibrosis contributes to worse quality of life, morbidity and mortality. Despite the high prevalence of certain co-morbidities in idiopathic pulmonary fibrosis, the optimal screening and management of many of these conditions remains unclear. The impact of co-morbidities on this patient population is becoming more apparent. Their relevance will only increase as significant effort is being made to develop novel therapeutics that will alter the disease trajectory of patients with idiopathic pulmonary fibrosis. The purpose of this review is to focus on the epidemiology, pathophysiology, diagnosis and management of select co-morbidities, including obstructive sleep apnoea, gastro-oesophageal reflux disease, pulmonary hypertension and depression, in idiopathic pulmonary fibrosis. PMID- 26365252 TI - Correction: Magnetophoresis of superparamagnetic nanoparticles at low field gradient: hydrodynamic effect. AB - Correction for 'Magnetophoresis of superparamagnetic nanoparticles at low field gradient: hydrodynamic effect' by Sim Siong Leong et al., Soft Matter, 2015, 11, 6968-6980. PMID- 26365253 TI - Dysglycaemia in small-for-gestational-age neonates: a matched case-control study in monochorionic twins. AB - OBJECTIVE: Small-for-gestational-age (SGA) neonates (birth weight <10th centile) are at higher risk of altered glucose homeostasis compared to appropriate for gestational age (AGA) neonates. The aim of this matched case-control study was to estimate the incidence of hypoglycaemia and/or hyperglycaemia in monochorionic (MC) twins with selective intrauterine growth restriction (sIUGR). METHODS: We included all MC twins with sIUGR (2002-2013). Neonates in the SGA group were matched with their AGA co-twin. We recorded the occurrence of hypoglycaemia and hyperglycaemia in the first 48 h after birth and studied the association with SGA. RESULTS: In this retrospective study were 126 twin pairs included. The incidence of hypoglycaemia in the SGA group and AGA group was 29.6% and 17.4%, respectively, hyperglycaemia occurred in 8.7% of the SGA neonates and in 2.6% of the AGA co-twins. Multivariate analysis showed an independent association of SGA with hypoglycaemia (OR 1.97, CI 1.23-3.18, p <= 0.01), but not with hyperglycaemia (OR 2.57, CI 1.64-10.28, p = 0.182). Low gestational age (GA) at birth (OR 1.65, CI 1.09-2.48, p = 0.02) showed an independent association with hyperglycaemia. CONCLUSIONS: The risk of hypoglycaemia is almost twofold higher in SGA neonates compared to their MC AGA twins. Low GA appeared to be an independent risk factor for hyperglycaemia in SGA neonates. PMID- 26365250 TI - Stimulation-induced Ca(2+) influx at nodes of Ranvier in mouse peripheral motor axons. AB - KEY POINTS: In peripheral myelinated axons of mammalian spinal motor neurons, Ca(2+) influx was thought to occur only in pathological conditions such as ischaemia. Using Ca(2+) imaging in mouse large motor axons, we find that physiological stimulation with trains of action potentials transiently elevates axoplasmic [C(2+)] around nodes of Ranvier. These stimulation-induced [Ca(2+)] elevations require Ca(2+) influx, and are partially reduced by blocking T-type Ca(2+) channels (e.g. mibefradil) and by blocking the Na(+)/Ca(2+) exchanger (NCX), suggesting an important contribution of Ca(2+) influx via reverse-mode NCX activity. Acute disruption of paranodal myelin dramatically increases stimulation induced [Ca(2+)] elevations around nodes by allowing activation of sub-myelin L type (nimodipine-sensitive) Ca(2+) channels. The Ca(2+) that enters myelinated motor axons during normal activity is likely to contribute to several signalling pathways; the larger Ca(2+) influx that occurs following demyelination may contribute to the axonal degeneration that occurs in peripheral demyelinating diseases. Activity-dependent Ca(2+) signalling is well established for somata and terminals of mammalian spinal motor neurons, but not for their axons. Imaging of an intra-axonally injected fluorescent [Ca(2+)] indicator revealed that during repetitive action potential stimulation, [Ca(2+)] elevations localized to nodal regions occurred in mouse motor axons from ventral roots, phrenic nerve and intramuscular branches. These [Ca(2+)] elevations (~ 0.1 MUm with stimulation at 50 Hz, 10 s) were blocked by removal of Ca(2+) from the extracellular solution. Effects of pharmacological blockers indicated contributions from both T-type Ca(2+) channels and reverse mode Na(+)/Ca(2+) exchange (NCX). Acute disruption of paranodal myelin (by stretch or lysophosphatidylcholine) increased the stimulation-induced [Ca(2+)] elevations, which now included a prominent contribution from L-type Ca(2+) channels. These results suggest that the peri nodal axolemma of motor axons includes multiple pathways for stimulation-induced Ca(2+) influx, some active in normally-myelinated axons (T-type channels, NCX), others active only when exposed by myelin disruption (L-type channels). The modest axoplasmic peri-nodal [Ca(2+)] elevations measured in intact motor axons might mediate local responses to axonal activation. The larger [Ca(2+) ] elevations measured after myelin disruption might, over time, contribute to the axonal degeneration observed in peripheral demyelinating neuropathies. PMID- 26365254 TI - Hunter-Gatherer Color Naming Provides New Insight into the Evolution of Color Terms. AB - Most people name the myriad colors in the environment using between two and about a dozen color terms, with great variation within and between languages. Investigators generally agree that color lexicons evolve from fewer terms to more terms, as technology advances and color communication becomes increasingly important. However, little is understood about the color naming systems at the least technologically advanced end of the continuum. The Hadza people of Tanzania are nomadic hunter-gatherers who live a subsistence lifestyle that was common before the advent of agriculture (see Supplemental Experimental Procedures, section I;), suggesting that the Hadzane language should be at an early stage of color lexicon evolution. When Hadza, Somali, and US informants named 23 color samples, Hadza informants named only the black, white, and red samples with perfect consensus. Otherwise, they used low-consensus terms or responded "don't know." However, even low-consensus color terms grouped test colors into lexical categories that aligned with those found in other world languages. Furthermore, information-theoretic analysis showed that color communication efficiency within the Hadza, Somali, and US language communities falls on the same continuum as other world languages. Thus, the structure of color categories is in place in Hadzane, even though words for many of the categories are not in general use. These results suggest that even very simple color lexicons include precursors of many color categories but that these categories are initially represented in a diverse and distributed fashion. PMID- 26365255 TI - Phylogenomics Reveals Convergent Evolution of Lifestyles in Close Relatives of Animals and Fungi. AB - The Opisthokonta are a eukaryotic supergroup divided in two main lineages: animals and related protistan taxa, and fungi and their allies [1, 2]. There is a great diversity of lifestyles and morphologies among unicellular opisthokonts, from free-living phagotrophic flagellated bacterivores and filopodiated amoebas to cell-walled osmotrophic parasites and saprotrophs. However, these characteristics do not group into monophyletic assemblages, suggesting rampant convergent evolution within Opisthokonta. To test this hypothesis, we assembled a new phylogenomic dataset via sequencing 12 new strains of protists. Phylogenetic relationships among opisthokonts revealed independent origins of filopodiated amoebas in two lineages, one related to fungi and the other to animals. Moreover, we observed that specialized osmotrophic lifestyles evolved independently in fungi and protistan relatives of animals, indicating convergent evolution. We therefore analyzed the evolution of two key fungal characters in Opisthokonta, the flagellum and chitin synthases. Comparative analyses of the flagellar toolkit showed a previously unnoticed flagellar apparatus in two close relatives of animals, the filasterean Ministeria vibrans and Corallochytrium limacisporum. This implies that at least four different opisthokont lineages secondarily underwent flagellar simplification. Analysis of the evolutionary history of chitin synthases revealed significant expansions in both animals and fungi, and also in the Ichthyosporea and C. limacisporum, a group of cell-walled animal relatives. This indicates that the last opisthokont common ancestor had a complex toolkit of chitin synthases that was differentially retained in extant lineages. Thus, our data provide evidence for convergent evolution of specialized lifestyles in close relatives of animals and fungi from a generalist ancestor. PMID- 26365256 TI - Humans Can Continuously Optimize Energetic Cost during Walking. AB - People prefer to move in ways that minimize their energetic cost. For example, people tend to walk at a speed that minimizes energy use per unit distance and, for that speed, they select a step frequency that makes walking less costly. Although aspects of this preference appear to be established over both evolutionary and developmental timescales, it remains unclear whether people can also optimize energetic cost in real time. Here we show that during walking, people readily adapt established motor programs to minimize energy use. To accomplish this, we used robotic exoskeletons to shift people's energetically optimal step frequency to frequencies higher and lower than normally preferred. In response, we found that subjects adapted their step frequency to converge on the new energetic optima within minutes and in response to relatively small savings in cost (<5%). When transiently perturbed from their new optimal gait, subjects relied on an updated prediction to rapidly re-converge within seconds. Our collective findings indicate that energetic cost is not just an outcome of movement, but also plays a central role in continuously shaping it. PMID- 26365257 TI - Active Interpersonal Touch Gives Rise to the Social Softness Illusion. AB - Social touch plays a powerful role in human life, with important physical and mental health benefits in development and adulthood. Touch is central in building the foundations of social interaction, attachment, and cognition, and early, social touch has unique, beneficial neurophysiological and epigenetic effects. The recent discovery of a separate neurophysiological system for affectively laden touch in humans has further kindled scientific interest in the area. Remarkably, however, little is known about what motivates and sustains the human tendency to touch others in a pro-social manner. Given the importance of social touch, we hypothesized that active stroking elicits more sensory pleasure when touching others' skin than when touching one's own skin. In a set of six experiments (total N = 133) we found that healthy participants, mostly tested in pairs to account for any objective differences in skin softness, consistently judged another's skin as feeling softer and smoother than their own skin. We further found that this softness illusion appeared selectively when the touch activated a neurophysiological system for affective touch in the receiver. We conclude that this sensory illusion underlies a novel, bodily mechanism of socio affective bonding and enhances our motivation to touch others. PMID- 26365259 TI - The Nrde Pathway Mediates Small-RNA-Directed Histone H3 Lysine 27 Trimethylation in Caenorhabditis elegans. AB - Small-RNA-mediated chromatin modifications have been widely studied in plants and S. pombe. However, direct evidence of small-RNA-guided sequence-specific chromatin alterations is scarce in animals. In C. elegans, the nuclear RNAi defective (Nrde) pathway functions to transport siRNA from the cytoplasm to the nucleus, modulate transcription elongation, induce histone H3 lysine 9 (H3K9) trimethylation, and mediate transgenerational inheritance of RNAi. Here, we show that both exogenous RNAi and NRDE-bound endogenous 22G RNAs can direct sequence specific histone H3 lysine 27 (H3K27) trimethylation at targeted loci through the Nrde pathway. The resulting H3K27me3 status can be inherited by progeny for multiple generations. piRNAs and WAGO-1-associated siRNAs induce H3K27 methylation as well. Interestingly, CSR-1-associated endogenous siRNAs fail to trigger H3K27 methylation, whereas exogenous provision of dsRNAs can induce H3K27 methylation at the CSR-1-targeted loci via the Nrde pathway. We further observed distinct genetic requirements of H3K9 and H3K27 trimethylation. Whereas set-25 and met-2 are required for K9 methylation, mes-2 is required for K27 methylation. The depletion of mes-2 leads to a nuclear RNAi defective phenotype. These results indicate that dsRNA-triggered chromatin modification is a sequence-specific response that engages the Nrde pathway in C. elegans. PMID- 26365260 TI - Fate of abstracts presented at the 2008 European Congress of Physical and Rehabilitation Medicine. AB - The subsequent full-text publication of abstracts presented at a scientific congress reflects the latter's scientific quality. The aim of this paper was to evaluate the publication rate for abstracts presented at the 2008 European Congress of Physical and Rehabilitation Medicine (ECPRM), characterize the publications and identify factors that were predictive of publication. It is a bibliography search. We used the PubMed database to search for subsequent publication of abstracts. We screened the abstracts' characteristics for features that were predictive of publication among abstracts features, such the status of the authors, the topic and the type of work. We performed univariate analyses and a logistic regression analysis. Of 779 abstracts presented at ECPRM 2008, 169 (21.2%) were subsequently published. The mean time to publication was 12+/-15.7 months and the mean impact factor of the publishing journals was 2.05+/-2.1. In a univariate analysis, university status (P<10-6), geographic origin (P=10-3), oral presentation (P<10-6), and original research (P<10-6) (and particularly multicentre trials [P<0.01] and randomized controlled trials [P=10-3]) were predictive of publication. In a logistic regression analysis, oral presentation (odds ratio [OR]=0.37) and university status (OR=0.36) were significant, independent predictors of publication. ECPRM 2008 publication rate and impact factor were relatively low, when compared with most other national and international conferences in this field. University status, the type of abstract and oral presentation were predictive of subsequent publication. PMID- 26365258 TI - An Olfactory Cilia Pattern in the Mammalian Nose Ensures High Sensitivity to Odors. AB - In many sensory organs, specialized receptors are strategically arranged to enhance detection sensitivity and acuity. It is unclear whether the olfactory system utilizes a similar organizational scheme to facilitate odor detection. Curiously, olfactory sensory neurons (OSNs) in the mouse nose are differentially stimulated depending on the cell location. We therefore asked whether OSNs in different locations evolve unique structural and/or functional features to optimize odor detection and discrimination. Using immunohistochemistry, computational fluid dynamics modeling, and patch clamp recording, we discovered that OSNs situated in highly stimulated regions have much longer cilia and are more sensitive to odorants than those in weakly stimulated regions. Surprisingly, reduction in neuronal excitability or ablation of the olfactory G protein in OSNs does not alter the cilia length pattern, indicating that neither spontaneous nor odor-evoked activity is required for its establishment. Furthermore, the pattern is evident at birth, maintained into adulthood, and restored following pharmacologically induced degeneration of the olfactory epithelium, suggesting that it is intrinsically programmed. Intriguingly, type III adenylyl cyclase (ACIII), a key protein in olfactory signal transduction and ubiquitous marker for primary cilia, exhibits location-dependent gene expression levels, and genetic ablation of ACIII dramatically alters the cilia pattern. These findings reveal an intrinsically programmed configuration in the nose to ensure high sensitivity to odors. PMID- 26365261 TI - Smoking habits are an independent prognostic factor in patients with lung cancer. AB - OBJECTIVES: The role of tobacco in the pathogenesis of lung cancer (LC) has been clearly established. Based on the epidemiological evidence that smoking may influence LC progression, we investigated the idea that smoking behavior could be associated with overall survival (OS) in this group of patients. METHODS: A total of 351 patients with LC (311 men and 40 women) were reviewed. Smoking status was assessed as tobacco users or non-users. To calculate pack-years of smoking, the average of number of cigarettes smoked per day was divided by 20 to give packs per day, and then multiplied by the total number of years of smoking. OS was the main outcome measure. RESULTS: The mean follow-up was 3.3 +/- 1.2 years. Kaplan Meier plots of OS by use of tobacco revealed significant differences by smoking status (log-rank = 5.44, P < 0.01), indicating a reduced survival rate in tobacco users. The effect on OS of the amount of cigarette smoking was also evident when we subdivided the former and current smokers into <=7 (mean value) pack-years and >7 pack-years groups (log-rank = 4.27, P < 0.05). After adjusting for all potential confounders, tobacco smoking retained its independent prognostic significance for OS (hazard ratio = 1.53, 95% confidence interval = 1.19-2.17, P = 0.02). CONCLUSIONS: Our data indicate that cigarette smoking is significantly associated with a poor prognosis among patients diagnosed with LC in a dose dependent manner. PMID- 26365262 TI - Dietary carbohydrate and lipid sources affect differently the oxidative status of European sea bass (Dicentrarchus labrax) juveniles. AB - This study aimed to evaluate the effects of dietary lipid source and carbohydrate content on the oxidative status of European sea bass (Dicentrarchus labrax) juveniles. For that purpose, four diets were formulated with fish oil (FO) and vegetable oils (VO) as the lipid source and with 20 or 0 % gelatinised starch as the carbohydrate source, in a 2*2 factorial design. Liver and intestine antioxidant enzyme activities (catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPX), glutathione reductase (GR), glucose-6-phosphate dehydrogenase (G6PD)), hepatic and intestinal lipid peroxidation (LPO), as well as hepatic oxidative stress index (OSI), were measured in fish fed the experimental diets for 73 d (n 9 fish/diet). Carbohydrate-rich diets promoted a decrease in hepatic LPO and OSI, whereas the lipid source induced no changes. Inversely, dietary lipid source, but not dietary carbohydrate concentration, affected LPO in the intestine. Lower intestinal LPO was observed in VO groups. Enzymes responsive to dietary treatments were GR, G6PD and CAT in the liver and GR and GPX in the intestine. Dietary carbohydrate induced GR and G6PD activities and depressed CAT activity in the liver. GPX and GR activities were increased in the intestine of fish fed VO diets. Overall, effects of diet composition on oxidative status were tissue-related: the liver and intestine were strongly responsive to dietary carbohydrates and lipid sources, respectively. Furthermore, different metabolic routes were more active to deal with the oxidative stress in the two organs studied. PMID- 26365263 TI - Towards the tailored design of benzotriazinyl-based organic radicals displaying a spin transition. AB - The mechanism of the phase transition of 1-phenyl-3-trifluoromethyl-1,4 dihydrobenzo[e][1,2,4]triazin-4-yl (1), the first reported triazinyl radical to present such a feature, is unveiled. In so doing, we identify the key ingredients that are crucial to enable the phase transition in this family of radicals, and how those can be exploited by a rational design of the spin-carrying units. PMID- 26365264 TI - How strong are the physiological theories on which Kinesio Taping is based? PMID- 26365265 TI - Very early mobilisation within 24 hours of stroke results in a less favourable outcome at 3 months [commentary 1]. PMID- 26365266 TI - Inspiratory muscle training is used in some intensive care units, but many training methods have uncertain efficacy: a survey of French physiotherapists. AB - QUESTIONS: How common is inspiratory muscle training by physiotherapists in the intensive care unit (ICU)? Which patients receive the training? What methods are used to administer the training? Is maximal inspiratory pressure used to evaluate the need for the training and the patient's outcome after training? DESIGN: Cross sectional survey of all ICUs in France. PARTICIPANTS: Two hundred and sixty-five senior physiotherapists. RESULTS: The response rate was 99% among eligible units. Therapist experience in ICU was significantly associated with the use of inspiratory muscle training (p=0.02). Therapists mainly used inspiratory muscle training either systematically or specifically in patients who failed to wean from mechanical ventilation. The training was used significantly more in non sedated patients (p<0.0001). The most commonly nominated technique that respondents claimed to use to apply the training was controlled diaphragmatic breathing (83% of respondents), whereas 13% used evidence-based methods. Among those who applied some form of inspiratory muscle training, 16% assessed maximal inspiratory pressure. Six respondents (2%, 95% CI 1 to 5) used both an evidence based method to administer inspiratory muscle training and the recommended technique for assessment of inspiratory muscle strength. CONCLUSION: Most physiotherapists in French ICUs who apply inspiratory muscle training use methods of uncertain efficacy without assessment of maximal inspiratory pressure. Further efforts need to be made in France to disseminate information regarding evidence based assessment and techniques for inspiratory muscle training in the ICU. The alignment of inspiratory muscle training practice with evidence could be investigated in other regions. PMID- 26365267 TI - Very early mobilisation within 24 hours of stroke results in a less favourable outcome at 3 months [Author's response]. PMID- 26365268 TI - Strategies to enhance self-efficacy and adherence to home-based pelvic floor muscle exercises did not improve adherence in women with urinary incontinence: a randomised trial. AB - QUESTION: Do strategies to enhance self-efficacy and exercise mastery affect adherence to home-based pelvic floor muscle exercises in women with urinary incontinence? DESIGN: Two-arm, parallel, randomised, controlled trial with intention-to-treat analysis. Randomisation was performed using computer-generated random numbers in five blocks of 20 women. PARTICIPANTS: Eighty-six women with stress, urgency or mixed urinary incontinence. INTERVENTION: All participants underwent three individual physiotherapy clinic visits at Day 0, 15 and 30, and 2 further months of home-based pelvic floor muscle exercises. The experimental group also received self-efficacy enhancing interventions, including a structured discussion on accomplishments and goals, a 9-minute video with testimonials, and a reminder. OUTCOME MEASURES: The primary outcome - adherence to at least 20 fast and 20 slow contractions every day - was evaluated with a structured questionnaire at 15, 30 and 90 days after enrolment and completion of a daily diary. A validated questionnaire was used to assess urinary incontinence. Self efficacy and pelvic floor muscle function were also measured. RESULTS: Seven women withdrew from each group before the Day-30 assessment. There was no difference in adherence to pelvic floor muscle exercises at 90 days between the groups (MD 0.5 points, 95% CI -1.1 to 2.1) on the questionnaire, which was scored from 2 to 21. At Day 90, 56% of the experimental group and 44% of the control group were performing the exercises every day. Adherence scores of both groups decreased during the 2-month follow-up period without any supervised physiotherapy session (p<0.05). The groups did not differ on the remaining secondary outcomes. CONCLUSION: Discussion of accomplishments and goals, a testimonial video and a reminder did not increase exercise adherence more than exercise mastery. TRIAL REGISTRATION: Brazilian Registry of Clinical Trials UTN:U1111-1128-8684. PMID- 26365269 TI - Very early mobilisation within 24 hours of stroke results in a less favourable outcome at 3 months [commentary 2]. PMID- 26365270 TI - NOAC or Warfarin for Atrial Fibrillation: Does Time in Therapeutic Range Matter? AB - Atrial fibrillation (AF) is the commonest cardiac arrhythmia currently affecting 1-2% of the general population, with stroke being one of its most fearsome complications. Dose-adjusted warfarin is an established treatment for reduction of thromboembolic risk but mandates dietary restrictions and need for routine blood monitoring. Novel oral anticoagulants (Dabigatran - patent: US20110082299A1, manufactured by Boehringer Ingelheim; Rivaroxaban - patent: US20150175590A1, manufactured by Bayer; Apixaban - patent: US20140335178A1, manufactured jointly by Pfizer and Bristol-Myers Squibb; Edoxaban - patent: WO2013026553A1, manufactured by Daiichi Sankyo) have recently been introduced that might provide at least equal reduction in thromboembolic risk to patients; negating the need for dietary restrictions and routine blood tests. The most recent National Institute of Health and Care Excellence, UK guidelines from August 2014 suggest consideration of one of the novel oral anticoagulants if the time in therapeutic range is less than 65%. In this study, the evidence for four novel oral anticoagulants is reviewed and the anticoagulation success with warfarin with atrial fibrillation and mechanical heart valves assessed in a large UK District General Hospital. Fifty-eight patients were identified with mechanical heart valve and 2737 patients with atrial fibrillation. Patients with atrial fibrillation had a significantly better TTR when compared with the patients included in the NOAC trials. Our results were similar with the Auricula registry. However, 25% of patients had TTR<65% and they would need to be considered for NOACs. Our data suggest that the degree of benefit seen in the NOAC trials might not be expected in our cohort of patients with atrial fibrillation. Interestingly, our patients with atrial fibrillation had a much better mean TTR of 76.4% and required less INR tests (12/year) compared to patients with mechanical heart valve who had a mean TTR of 61.4% and required more INR tests (26/year). PMID- 26365271 TI - PGD2 stimulates osteoprotegerin synthesis via AMP-activated protein kinase in osteoblasts: Regulation of ERK and SAPK/JNK. AB - AMP-activated protein kinase (AMPK), a key enzyme sensing cellular energy metabolism, is currently known to regulate multiple metabolic pathways. Osteoprotegerin plays a pivotal role in the regulation of bone metabolism by inhibiting osteoclast activation. We have previously reported that prostaglandin D2 (PGD2) stimulates the synthesis of osteoprotegerin through the activation of p38 mitogen-activated protein (MAP) kinase, p44/p42 MAP kinase and stress activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) in osteoblast-like MC3T3-E1 cells. On the basis of these findings, we herein investigated the implication of AMPK in PGD2-stimulated osteoprotegerin synthesis in these cells. PGD2 induced the phosphorylation of AMPKalpha (Thr-172) and AMPKbeta (Ser-108), and the phosphorylation of acetyl-coenzyme A carboxylase, a direct AMPK substrate. Compound C, an AMPK inhibitor, which suppressed the phosphorylation of acetyl-coenzyme A carboxylase, significantly attenuated both the release and the mRNA levels of osteoprotegerin stimulated by PGD2. The PGD2-induced phosphorylation of p44/p42 MAP kinase and SAPK/JNK but not p38 MAP kinase were markedly inhibited by compound C. These results strongly suggest that AMPK regulates the PGD2-stimulated osteoprotegerin synthesis at a point upstream of p44/p42 MAP kinase and SAPK/JNK in osteoblasts. PMID- 26365272 TI - Recent advances in the management of oral and maxillofacial trauma. AB - This review summarises recently published papers on maxillofacial trauma in 2 widely read journals: the British Journal of Oral and Maxillofacial Surgery (BJOMS) and the International Journal of Oral and Maxillofacial Surgery (IJOMS). Since a large proportion of the injuries seen in oral and maxillofacial surgery (OMFS) departments are fractures of the facial skeleton, we primarily focus on their assessment and treatment, but also cover problems that affect the temporomandibular joint (TMJ) (including ankylosis), military injuries, polytrauma, and the use of perioperative drugs. Between 2012 and 2013, 121 articles were published in the 2 journals. Most of the research concerned mandibular fractures, particularly those involving the condyle, but epidemiological studies and midfacial fractures were also well represented. Even though the incidence of facial injury is high, it is difficult to collect data particularly when long-term evaluation is required, as rates of compliance and attendance at follow up tend to be low. The number of large-scale studies was therefore small. A concerted effort to collaborate nationally and across specialties to undertake larger studies will help to improve outcomes. PMID- 26365273 TI - Spinal Nerve Root Enhancement on MRI Scans in Children: A Review. AB - Spinal nerve root enhancement in pediatric patients is generally nonspecific, and clinical and laboratory correlation is essential. Nerve root enhancement indicates lack of integrity of the blood-nerve barrier. In this review, we will present a range of pediatric conditions that can present with spinal nerve root enhancement including inflammatory, infectious, hereditary, and neoplastic causes. Familiarity with the various pathologic entities associated with spinal nerve root enhancement is important for a concise differential diagnosis in the appropriate clinical setting. This will avoid unnecessary additional investigations. PMID- 26365274 TI - Pertussis toxin reduces calcium influx to protect ischemic stroke in a middle cerebral artery occlusion model. AB - Increased calcium influx secondary to glutamate induced excitotoxicity initiates and potentiates devastating pathological changes following ischemic stroke. Pertussis toxin (PTx), a G-protein blocker, is known to suppress intracellular calcium accumulation. We hypothesize that PTx can protect against stroke by blocking calcium influx. In a permanent middle cerebral artery occlusion model, PTx (1000 ng) was given intraperitoneally 30 min after inducing stroke. Magnetic Resonance Imaging of perfusion and T2-weighted brain scans were obtained to evaluate cerebral blood flow (CBF) and infarct volume. Primary neuronal culture was used to test glutamate induced excitotoxicity and calcium influx. We established a non-linear exponential curve model to minimize variations in animal cerebrovasculature. A reduction of 40-60% in relative CBF was a critical window where infarct volume started to increase as rCBF reduced. PTx showed maximal effects in reducing infarct volume at this window. In vitro studies further demonstrated PTx increased neuronal cell survival by decreasing glutamate-induced calcium influx into neurons and preventing neurons from apoptosis. PTx salvages the ischemic penumbra by blocking calcium influx. This provides us a new mechanism upon which experimental therapies can be explored to treat ischemic stroke. In ischemic stroke, excessive glutamate binds to AMPA receptor that depolarizes calcium channel and/ or NMDA receptor. Both of them allow calcium to enter the cell. The overload of calcium triggers cellular cascade that includes Caspase activation and release, leading to pre-mature cell death. We have demonstrated that PTx, a G-protein inhibitor, blocks calcium entry which in turn prevents further cellular damage. PMID- 26365275 TI - Histone Deacetylase Gene Expression Following Binge Alcohol Consumption in Rats and Humans. AB - BACKGROUND: Alcohol binge drinking is one of the most common patterns of excessive alcohol use and recent data would suggest that histone deacetylases (HDACs) gene expression profiling could be useful as a biomarker for psychiatric disorders. METHODS: This study aimed to characterize the gene expression patterns of Hdac 1-11 in samples of rat peripheral blood, liver, heart, prefrontal cortex, and amygdala following repeated binge alcohol consumption and to determine the parallelism of Hdac gene expression between rats and humans in peripheral blood. To accomplish this goal, we examined Hdac gene expression following 1, 4, or 8 alcohol binges (3 g/kg, orally) in the rat, in patients who were admitted to the hospital emergency department for acute alcohol intoxication, and in rats trained in daily operant alcohol self-administration. RESULTS: We primarily found that acute alcohol binging reduced gene expression (Hdac1-10) in the peripheral blood of alcohol-naive rats and that this effect was attenuated following repeated alcohol binges. There was also a reduction of Hdac gene expression in the liver (Hdac2,4,5), whereas there was increased expression in the heart (Hdac1,7,8) and amygdala (Hdac1,2,5). Additionally, increased blood alcohol concentrations were measured in rat blood at 1 to 4 hours following repeated alcohol binging, and the only group that developed hepatic steotosis (fatty liver) were those animals exposed to 8 alcohol binge events. Finally, both binge consumption of alcohol in humans and daily operant alcohol self-administration in rats increased Hdac gene expression in peripheral blood. CONCLUSIONS: Our results suggest that increases in HDAC gene expression within the peripheral blood are associated with chronic alcohol consumption, whereas HDAC gene expression is reduced following initial exposure to alcohol. PMID- 26365276 TI - Feasibility of an Alternative Option for the Management of Male Lower Urinary Tract Symptoms. AB - PURPOSE: We determine if men with self-reported lower urinary tract symptoms can make a correct decision to use an over-the-counter alpha-1 blocker. Furthermore, we assess the frequency of medically significant conditions presenting with urinary symptoms in these consumers. MATERIALS AND METHODS: Subjects reviewed a mock-up of an over-the-counter product for male lower urinary tract symptoms (part 1). Subjects who selected the product underwent urine dipstick testing and male subjects completed the AUA Symptom Index (part 2). Urological assessment was conducted in women; in men younger than 45 years; men 45 years old or older who reported "Do Not Use" symptoms listed on the over-the-counter label; who had glucose, leukocytes and/or blood in their urine; or had an AUA-SI score of 20 or greater. RESULTS: Of the 1,967 subjects enrolled 1,953 completed part 1 (men/women 1,697/256), 1,311 (1,294/17) entered part 2 and 1,289 (1,274/15) were evaluated. Frequently reported baseline medical conditions were hypertension (45.8%/46.7%) and dyslipidemia (36.4%/60.0%). Lower urinary tract symptoms were present for more than 3 years in 47.6% of men and 40% of women. Mean AUA-SI score was 18.9. Urine dipstick results were positive in 20.9% of men. Overall 729 men and 12 women underwent urological assessment, and 517 (70.9%) men had urologist confirmed lower urinary tract symptoms while 200 (27.4%) did not. Newly diagnosed medically significant conditions causing/contributing to lower urinary tract symptoms were identified in 21 (2.9%) men and 2 (16.7%) women. CONCLUSIONS: Most men correctly selected the over-the-counter product for the management of lower urinary tract symptoms/benign prostatic hyperplasia, while most women correctly deselected to use the product. Since few men had undiagnosed medically significant conditions causing/contributing to urinary symptoms, the risk of harm due to incorrect selection was low. PMID- 26365277 TI - Research into cancer metabolomics: Towards a clinical metamorphosis. AB - The acknowledgement that metabolic reprogramming is a central feature of cancer has generated high expectations for major advances in both diagnosis and treatment of malignancies through addressing metabolism. These have so far only been partially fulfilled, with only a few clinical applications. However, numerous diagnostic and therapeutic compounds are currently being evaluated in either clinical trials or pre-clinical models and new discoveries of alterations in metabolic genes indicate future prognostic or other applicable relevance. Altogether, these metabolic approaches now stand alongside other available measures providing hopes for the prospects of metabolomics in the clinic. Here we present a comprehensive overview of both ongoing and emerging clinical, pre clinical and technical strategies for exploiting unique tumour metabolic traits, highlighting the current promises and anticipations of research in the field. PMID- 26365279 TI - Avian metapneumovirus infection of chicken and turkey tracheal organ cultures: comparison of virus-host interactions. AB - Avian metapneumovirus (aMPV) is a pathogen with worldwide distribution, which can cause high economic losses in infected poultry. aMPV mainly causes infection of the upper respiratory tract in both chickens and turkeys, although turkeys seem to be more susceptible. Little is known about virus-host interactions at epithelial surfaces after aMPV infection. Tracheal organ cultures (TOC) are a suitable model to investigate virus-host interaction in the respiratory epithelium. Therefore, we investigated virus replication rates and lesion development in chicken and turkey TOC after infection with a virulent aMPV subtype A strain. Aspects of the innate immune response, such as interferon-alpha and inducible nitric oxide synthase mRNA expression, as well as virus-induced apoptosis were determined. The aMPV-replication rate was higher in turkey (TTOC) compared to chicken TOC (CTOC) (P < 0.05), providing circumstantial evidence that indeed turkeys may be more susceptible. The interferon-alpha response was down regulated from 2 to 144 hours post infection in both species compared to virus free controls (P < 0.05); this was more significant for CTOC than TTOC. Inducible nitric oxide synthase expression was significantly up-regulated in aMPV-A infected TTOC and CTOC compared to virus-free controls (P < 0.05). However, the results suggest that NO may play a different role in aMPV pathogenesis between turkeys and chickens as indicated by differences in apoptosis rate and lesion development between species. Overall, our study reveals differences in innate immune response regulation and therefore may explain differences in aMPV - A replication rates between infected TTOC and CTOC, which subsequently lead to more severe clinical signs and a higher rate of secondary infections in turkeys. PMID- 26365278 TI - Stepwise substrate translocation mechanism revealed by free energy calculations of doxorubicin in the multidrug transporter AcrB. AB - AcrB is the inner membrane transporter of the tripartite multidrug efflux pump AcrAB-TolC in E. coli, which poses a major obstacle to the treatment of bacterial infections. X-ray structures have identified two types of substrate-binding pockets in the porter domains of AcrB trimer: the proximal binding pocket (PBP) and the distal binding pocket (DBP), and suggest a functional rotating mechanism in which each protomer cycles consecutively through three distinct conformational states (access, binding and extrusion). However, the details of substrate binding and translocation between the binding pockets remain elusive. In this work, we performed atomic simulations to obtain the free energy profile of the translocation of an antibiotic drug doxorubicin (DOX) inside AcrB. Our simulation indicates that DOX binds at the PBP and DBP with comparable affinities in the binding state protomer, and overcomes a 3 kcal/mol energy barrier to transit between them. Obvious conformational changes including closing of the PC1/PC2 cleft and shrinking of the DBP were observed upon DOX binding in the PBP, resulting in an intermediate state between the access and binding states. Taken together, the simulation results reveal a detailed stepwise substrate binding and translocation process in the framework of functional rotating mechanism. PMID- 26365280 TI - Corrigendum. PMID- 26365282 TI - Catalyst-free vapour-solid technique for deposition of Bi2Te3 and Bi2Se3 nanowires/nanobelts with topological insulator properties. AB - We present a simple two-stage vapour-solid synthesis method for the growth of bismuth chalcogenide (Bi2Te3, Bi2Se3) topological insulator nanowires/nanobelts by using Bi2Se3 or Bi2Te3 powders as source materials. During the first stage of the synthesis process nanoplateteles, serving as "catalysts" for further nanowire/nanobelt growth, are formed. At a second stage of the synthesis, the introduction of a N2 flow at 35 Torr pressure in the chamber induces the formation of free standing nanowires/nanobelts. The synthesised nanostructures demonstrate a layered single-crystalline structure and Bi : Se and Bi : Te ratios 40 : 60 at% for both Bi2Se3 and Bi2Te3 nanowires/nanobelts. The presence of Shubnikov de Haas oscillations in the longitudinal magneto-resistance of the nanowires/nanobelts and their specific angular dependence confirms the existence of 2D topological surface states in the synthesised nanostructures. PMID- 26365281 TI - Review article: pharmacological aspects of anti-TNF biosimilars in inflammatory bowel diseases. AB - BACKGROUND: Anti-tumour necrosis factor (anti-TNF) monoclonal antibodies have shown efficacy in inflammatory bowel diseases (IBD). As these therapies lose patent protection, biosimilar versions of the originator products are being developed, such as the infliximab biosimilar CT-P13; however, some uncertainty exists regarding their pharmacology in IBD. AIM: To review the literature on anti TNF biosimilars focusing on pharmacokinetics, pharmacodynamic properties and comparative effectiveness, related to their use in IBD. METHODS: A PubMed literature search was performed using the following terms individually or in combination: 'biosimilars,' 'CT-P13,' 'Crohn's disease,' 'inflammatory bowel disease,' 'ulcerative colitis,' 'anti-TNFalpha therapy,' 'infliximab,' 'adalimumab,' 'pharmacokinetics,' 'immunogenicity.' RESULTS: Bioequivalence of CT P13 and infliximab was shown in ankylosing spondylitis (AS) and therapeutic equivalence in rheumatoid arthritis (RA). Preliminary results of CT-P13 in IBD come from small post-marketing registries and case series with a relatively short term follow-up period and suggest comparable efficacy and safety to infliximab. Inter- and intra-individual differences in exposure and response are well known for the original molecules but dosing regimens and concomitant medications are different for RA compared to IBD, limiting the ability to translate some of the pharmacology data in RA to IBD. Uncertainty exists about cross-reactivity of anti drug antibodies and whether similar exposure-response relationships will be observed for biosimilars and efficacy thresholds for therapeutic drug monitoring can be used interchangeably. CONCLUSIONS: It is likely that biosimilars will be widely used for the treatment of IBD due to their cost savings and comparable efficacy. Nevertheless, robust post-marketing studies and pharmacovigilance are warranted in the coming years. PMID- 26365283 TI - The impact of the EU Directive on patients' rights and cross border health care in Malta. AB - The patients' rights and cross-border health care directive was implemented in Malta in 2013. Malta's transposition of the directive used the discretionary elements allowable to retain national control on cross-border care to the fullest extent. This paper seeks to analyse the underlying dynamics of this directive on the Maltese health care system through the lens of key health system stakeholders. Thirty-three interviews were conducted. Qualitative content analysis of the interviews reveals six key themes: fear from the potential impact of increased patient mobility, strategies employed for damage control, opportunities exploited for health system reform, moderate enhancement of patients' rights, negligible additional patient mobility and unforeseen health system reforms. The findings indicate that local stakeholders expected the directive to have significant negative effects and adopted measures to minimise these effects. In practice the directive has not affected patient mobility in Malta in the first months following its implementation. Government appears to have instrumentalised the implementation of the directive to implement certain reforms including legislation on patients' rights, a health benefits package and compulsory indemnity insurance. Whilst the Maltese geo-demographic situation precludes automatic generalisation of the conclusions from this case study to other Member States, the findings serve to advance our understanding of the mechanisms through which European legislation on health services is influencing health systems, particularly in small EU Member States. PMID- 26365284 TI - Reduced facial expressiveness in Parkinson's disease: A pure motor disorder? AB - BACKGROUND AND AIMS: Impaired emotional facial expressiveness is an important feature in Parkinson's disease (PD). Although there is evidence of a possible relationship between reduced facial expressiveness and altered emotion recognition or imagery in PD, it is unknown whether other aspects of the emotional processing, such as subjective emotional experience (alexithymia), might influence hypomimia in this condition. In this study wee aimed to investigate possible relationship between reduced facial expressiveness and altered emotion processing (including facial recognition and alexithymia) in patients with PD. METHODS: Forty PD patients and seventeen healthy controls were evaluated. Facial expressiveness was rated on video recordings, according to the UPDRS-III item 19 and using an ad hoc scale assessing static and dynamic facial expression and posed emotions. Six blind raters evaluated the patients' videos. Emotion facial recognition was tested using the Ekman Test; alexithymia was assessed using Toronto Alexithymia Scale (TAS-20). RESULTS: PD patients had a significantly reduced static and dynamic facial expressiveness and a deficit in posing happiness and surprise. They performed significantly worse than healthy controls in recognizing surprise (p=0.03). The Ekman total score positively correlated with the global expressiveness (R^2=0.39, p=0.01) and with the expressiveness of disgust (R^2=0.32, p=0.01). The occurrence of alexithymia was not different between PD patients and HC; however, a significant negative correlation between the expressiveness of disgust was found for a subscore of TAS (R^2=-.447, p=0.007). CONCLUSIONS: Reduced facial expressiveness in PD may be in part related to difficulties with emotional recognition in a context of an unimpaired subjective emotional experience. PMID- 26365285 TI - Cervical and ocular vestibular evoked potentials in Machado-Joseph disease: Functional involvement of otolith pathways. AB - INTRODUCTION: Machado-Joseph disease is defined as an autosomal dominant ataxic disorder caused by degeneration of the cerebellum and its connections and is associated with a broad range of clinical symptoms. The involvement of the vestibular system is responsible for several symptoms and signs observed in the individuals affected by the disease. We measured cervical and ocular vestibular evoked myogenic potentials in a sample of Machado-Joseph disease patients in order to assess functional pathways involved. METHODS: Bilateral measures of cervical and ocular vestibular evoked myogenic potentials (cVEMP and oVEMP) were obtained from 14 symptomatic patients with genetically proven Machado-Joseph disease and compared with those from a control group of 20 healthy subjects. RESULTS: Thirteen (93%) patients showed at least one abnormal test result; oVEMP and cVEMP responses were absent in 17/28 (61%) and 11/28 (39%) measures, respectively; and prolonged latency of cVEMP was found in 3/28 (11%) measures. Of the 13 patients with abnormal responses, 9/13 (69%) patients showed discordant abnormal responses: four with absent oVEMP and present cVEMP, two with absent cVEMP and present oVEMP, and three showed unilateral prolonged cVEMP latencies. CONCLUSION: Both otolith-related vestibulocollic and vestibulo-ocular pathways are severely affected in Machado-Joseph disease patients evaluated by VEMPs. PMID- 26365286 TI - Hyperthermic preconditioning severely accelerates neuronal damage in the gerbil ischemic hippocampal dentate gyrus via decreasing SODs expressions. AB - It is well known that neurons in the dentate gyrus (DG) of the hippocampus are resistant to short period of ischemia. Hyperthermia is a proven risk factor for cerebral ischemia and can produce more extensive brain damage related with mortality rates. The aim of this study was to examine the effect of hyperthermic conditioning (H) on neuronal death, gliosis and expressions of SODs as anti oxidative enzymes in the gerbil DG following 5 min-transient cerebral ischemia. The animals were randomly assigned to 4 groups: 1) (N+sham)-group was given sham operation with normothermia (N); 2) (N+ischemia)-group was given 5 min-transient ischemia with N; 3) (H+sham)-group was given sham-operation with H; and 4) (H+ischemia)-group was given 5 min-transient cerebral ischemia with H. H (39+/ 0.5 degrees C) was induced by subjecting the animals to a heating pad for 30 min before and during the operation. In the (N+ischemia)-groups, a significant neuronal death was observed in the polymorphic layer (PL) from 1 day after ischemia-reperfusion. In the (H+ischemia)-groups, neuronal death was also observed in the PL from 1day post-ischemia; the degree of the neuronal death was severer than that in the (N+ischemia)-groups. In addition, we examined the gliosis of astrocytes and microglia using anti-glial fibrillary acidic protein (GFAP) and anti- ionized calcium-binding adapter molecule 1 (Iba-1). GFAP(+) and Iba-1(+) glial cells were much more activated in the (H+ischemia)-groups than those in the (N+ischemia)-groups. On the other hand, immunoreactivities and levels of SOD1 rather than SOD2 were significantly lower in the (H+ischemia) groups than those in the (N+ischemia)-groups. In brief, on the basis of our findings, we suggest that cerebral ischemic insult with hyperthermic conditioning brings up severer neuronal damage and gliosis in the polymorphic layer through reducing SOD1 expression rather than SOD2 expression in the DG. PMID- 26365287 TI - Successful Vim targeting for mixed essential and parkinsonian tremor using intraoperative MRI. PMID- 26365288 TI - Effects of low doses of Tat-PIM2 protein against hippocampal neuronal cell survival. AB - Oxidative stress is considered a major factor in various neuronal diseases including ischemia-reperfusion injury. Proviral Integration Moloney 2 (PIM2) proteins, one of the families of PIM kinases, play crucial roles in cell survival. However, the functions of PIM2 protein against ischemia are not understood. Therefore, the protective effects of PIM2 against oxidative stress induced hippocampal HT22 cell death and brain ischemic injury were evaluated using Tat-PIM2, a cell permeable fusion protein. Tat-PIM2 protein transduced into hippocampal HT22 cells. Low doses of transduced Tat-PIM2 protein protected against oxidative stress-induced cell death including DNA damage and markedly inhibited the activation of mitogen activated protein kinase (MAPKs), NF-kappaB and the expression levels of Bax protein. Furthermore, Tat-PIM2 protein transduced into the CA1 region of the hippocampus and significantly prevented neuronal cell death in an ischemic insult animal model. These results indicated that low doses of Tat-PIM2 protein protects against oxidative stress-induced neuronal cell death, suggesting low doses of Tat-PIM2 protein provides a potential therapeutic agent against oxidative stress-induced neuronal diseases including ischemia. PMID- 26365289 TI - Highly effective reduced toxicity dose-intensive pilot protocol for non metastatic limb osteogenic sarcoma (SCOS 89). AB - PURPOSE: Aggressive chemotherapy protocols for non-metastatic limb osteosarcoma have improved histological response without affecting prognosis. This study evaluated the toxicity and outcome of a dose-intensive, high-dose 3- to 5-drug pilot protocol, SCOS 89. METHODS: The cohort included 26 patients (14 male; ages 6.5-22 years) with non-metastatic limb osteosarcoma treated at a tertiary pediatric medical center between 1989 and 2013. Preoperatively, patients received two courses of once-weekly pulses of high-dose methotrexate (12-30 g/m(2)) for 2 weeks; doxorubicin (90 mg/m(2)) with dexrazoxane, combined with cisplatin (200 mg/m(2)), was added in week 3. Following methotrexate, 760 mg/m(2) of folinic acid was administered. Postoperative chemotherapy was continued to a total of 14 courses of methotrexate, doxorubicin (up to a total dose of 360 mg/m(2)), and cisplatin (up to a total dose of 560 mg/m(2)). If toxicity occurred or <90 % tumor necrosis, ifosfamide (12 g/m(2)) plus etoposide (500 mg/m(2)) was substituted for doxorubicin, cisplatin, or methotrexate. Toxicity and death rates were calculated. RESULTS: All patients underwent definitive limb salvage surgery. Six patients died of infection, recurrent disease, or secondary malignancy. Median follow-up was 100 months (range 2-290). Event-free and overall survival rates, respectively, were 88 and 96 % at 2 years, 80 and 87.6 % at 5 years, 80 and 78 % at 10 years. Eleven patients required ifosfamide/etoposide substitution. One patient had a transient decreased left ventricular ejection fraction. Two patients developed acute nephrotoxicity during therapy, but no neurotoxicity. Seven patients had hearing impairment. CONCLUSIONS: The SCOS 89 yields a high event-free survival rate with reduced nephro-/neuro-/cardiotoxicity in patients with non-metastatic limb osteosarcoma. PMID- 26365290 TI - Population pharmacokinetics and dosing implications for cobimetinib in patients with solid tumors. AB - PURPOSE: To characterize cobimetinib pharmacokinetics and evaluate impact of clinically relevant covariates on cobimetinib pharmacokinetics. METHODS: Plasma samples (N = 4886) were collected from 487 patients with various solid tumors (mainly melanoma) in three clinical studies (MEK4592g, NO25395, GO28141). Cobimetinib was administered orally, once daily on either a 21-day-on/7-day-off, 14-day-on/14-day-off or 28-day-on schedule in a 28-day dosing cycle as single agent or in combination with vemurafenib. Cobimetinib doses ranged from 2.1 to 125 mg. NONMEM was used for pharmacokinetic analysis. RESULTS: A linear two compartment model with first-order absorption, lag time and first-order elimination described cobimetinib pharmacokinetics. The typical estimates (inter individual variability) of apparent clearance (CL/F), central volume of distribution (V2/F) and terminal half-life were 322 L/day (58 %), 511 L (49 %) and 2.2 days, respectively. Inter-occasion variability on relative bioavailability was estimated at 46 %. CL/F decreased with age. V2/F increased with body weight (BWT). However, the impact of age and BWT on cobimetinib steady state exposure (peak and trough concentrations and AUC following the recommended daily dose of 60 mg 21-day-on/7-day-off) was limited (<25 % changes across the distribution of age and BWT). No significant difference in cobimetinib pharmacokinetics or steady-state exposure was observed between patient subgroups based on sex, renal function, ECOG score, hepatic function tests, race, region, cancer type, and co-administration of moderate and weak CYP3A inducers or inhibitors and vemurafenib. CONCLUSION: A population pharmacokinetic model was developed for cobimetinib in cancer patients. Covariates had minimal impact on steady-state exposure, suggesting no need for dose adjustments and supporting the recommended dose for all patients. PMID- 26365291 TI - When a Common Language Is Not Enough: Transcreating Cancer 101 for Communities in Puerto Rico. AB - In Puerto Rico (PR), cancer is the leading cause of death. Previous research has identified the need for cancer education in PR. Using culturally adapted cancer curricula to train local health educators may effectively increase cancer education and reduce health disparities. This article describes the three-phase process used to transcreate the Cancer 101 curriculum to train Master of Public Health (MPH) students to educate PR communities. First, an expert panel collaboratively reviewed the curriculum for content, legibility, utility, and colloquialisms. Recommendations included incorporating local references and resources, replacing words and examples with culturally relevant topics, and updating objectives and evaluation items. Subsequent focus groups with 10 MPH students assessed the adaptation's strengths, weaknesses, and utility for future trainees. Participants were satisfied with the curriculum's overall adaptation, ease of use, and listed resources; further improvements were suggested for all modules. Final expert panel revisions highlighted minor feedback, with the final curriculum containing nine transcreated modules. The transcreation process identified the need for changes to content and cultural translation. Changes were culturally and literacy-level appropriate, represented PR's social context, and were tailored for future trainees to successfully deliver cancer education. Findings highlight the importance of adapting Spanish educational materials across Hispanic sub-groups. PMID- 26365292 TI - Robust half-metallicity and topological aspects in two-dimensional Cu-TPyB. AB - Half-metallicity due to the coexistence of metallic nature for one spin component and insulating nature for the other is a base of spintronics devices, but was only achieved in few materials. From first-principles calculations, we demonstrate that a recently-synthesized two-dimensional organometallic framework of 1,3,5-tris(pyridyl)benzene and Cu atoms (Cu-TPyB) has robust half-metallicity. High electron velocity in one spin channel at Dirac point and a relatively large band gap in the other make the material meeting the demand of filtering the current into a single spin component. Moreover, spin-orbit coupling induces topologically nontrivial band gaps in the vicinity of the Fermi level, which are implementable for achieving quantum anomalous Hall effect in a low temperature range (<8 K). PMID- 26365293 TI - Maternal Health-Seeking on Behalf of Low-Income Children. AB - BACKGROUND: Women receiving Medicaid account for almost one-third of the childbearing population in the United States, an extensive investment for federal and state governments. Gaps and conflicting research results exist that explain/predict maternal health-seeking behavior for vulnerable children. Public health nurses (PHN) need evidence to design interventions that improve maternal health-seeking and child health outcomes. The purpose of this study was to examine factors: maternal (key influences), child, and household that contribute to maternal health-seeking behavior. METHODS: The design was a descriptive, correlational, longitudinal study (n = 1,141 mother-child dyads). RESULTS: Children were more likely to receive preventive medical care if they had a medical condition (OR: 1.60, p < .01) and had access to private transportation (OR: 1.49, p < .05). Children of married mothers (OR: 1.51, p < .01) and access to private transportation (OR: 1.47, p < .05) received more preventive dental care. African-American mothers (OR: 0.61, p < .01) and mothers with higher self reported health status (OR: 0.84, p < .05) sought less illness-related medical child health services (CHS). CONCLUSION: Maternal health-seeking behavior in low income households is complex. Predictors may depend on whether care is preventive or illness-related, medical, or dental. Further study should clarify what factors predict what type of CHS use to better specify PHN interventions. PMID- 26365294 TI - Brain-derived neurotrophic factor mediates neuroprotection against Abeta-induced toxicity through a mechanism independent on adenosine 2A receptor activation. AB - Brain-derived neurotrophic factor (BDNF) promotes neuronal survival through TrkB FL activation. The activation of adenosine A2A receptors (A2AR) is essential for most of BDNF-mediated synaptic actions, such as synaptic plasticity, transmission and neurotransmitter release. We now aimed at evaluating the A2AR influence upon BDNF-mediated neuroprotection against Abeta25-35 toxicity in cultured neurons. Results showed that BDNF increases cell survival and reduces the caspase-3 and calpain activation induced by amyloid-beta (Abeta) peptide, in a mechanism probably dependent on PLCgamma pathway. This BDNF-mediated neuroprotection is not affected by A2AR activation or inhibition. Moreover neither activation nor inhibition of A2AR, per se, significantly influenced Abeta-induced neuronal death on calpain-mediated cleavage of TrkB induced by Abeta. In conclusion, these results suggest that, in opposition to the fast synaptic actions of BDNF, the neuroprotective actions of this neurotrophin against a strong Abeta insult do not require the activation of A2AR. PMID- 26365296 TI - Semaphorin signaling in bone. AB - Semaphorin molecules regulate cell adhesion and motility in a wide variety of cell types and are therefore involved in numerous processes including axon guidance, angiogenesis, cardiogenesis, tumor growth, and immune response. Increasing evidence points to a role of transmembrane, membrane-associated and soluble semaphorins during bone development as well as in the control of normal bone homeostasis. Within bone, semaphorins are implicated in the communication between different cell types by relaying signals in an autocrine or paracrine way. Semaphorins are not only involved in bone resorption but also in bone formation. Therefore, targeting semaphorin-induced signaling in bone may constitute an interesting new therapeutic strategy in osteoporosis. However, all the pioneering research on semaphorins is performed in mice and it remains to be established to what extent semaphorin signaling pathways are conserved between mice and men. In addition, knowledge of semaphorin signaling in bone mostly arises from loss/gain of function studies of one single semaphorin and/or receptor. However, different semaphorin molecules are co-expressed in bone and their signaling pathways are likely to interact in a complex and coherent way that needs proper understanding before targeting semaphorin signaling can be therapeutically exploited. PMID- 26365295 TI - Enzyme-Instructed Intracellular Molecular Self-Assembly to Boost Activity of Cisplatin against Drug-Resistant Ovarian Cancer Cells. AB - Anticancer drug resistance demands innovative approaches that boost the activity of drugs against drug-resistant cancers without increasing the systemic toxicity. Here we show the use of enzyme-instructed self-assembly (EISA) to generate intracellular supramolecular assemblies that drastically boost the activity of cisplatin against drug-resistant ovarian cancer cells. We design and synthesize small peptide precursors as the substrates of carboxylesterase (CES). CES cleaves the ester bond pre-installed on the precursors to form the peptides that self assemble in water to form nanofibers. At the optimal concentrations, the precursors themselves are innocuous to cells, but they double or triple the activity of cisplatin against the drug-resistant ovarian cancer cells. This work illustrates a simple, yet fundamental, new way to introduce non-cytotoxic components into combination therapies with cisplatin without increasing the systemic burden or side effects. PMID- 26365297 TI - Kidney injury owing to Streptococcus pneumoniae infection in critically ill infants and children: report of four cases. AB - Streptococcus pneumoniae sepsis has high morbidity, particularly if complicated by renal injury. Four patients with S. pneumonia invasive infections complicated by renal disorders are presented. The first case was an 18-month-old girl with pneumococcal empyema complicated by haemolytic uraemic (HUS) syndrome. She made a full recovery after mechanical ventilation, inotropic support and haemodiafiltration. The second was a 4-year-old boy who presented with acute post infectious glomerulonephritis associated with bilateral pneumococcal pneumonia. He too made a complete recovery. The third was a newborn girl with pneumococcal meningitis complicated by acute respiratory distress syndrome and acute renal failure. The fourth patient was an 8-month-old boy with pneumococcal pneumonia and meningitis complicated by HUS and with fulminant thrombotic thrombocytopenic purpura. Despite full support including mechanical ventilation and haemodiafiltration, he died 4 days after admission. On follow-up, all three survivors recovered completely from their pulmonary symptoms and had normal renal function and cardio-circulatory status in the mid-term. PMID- 26365298 TI - Affinity imaging mass spectrometry (AIMS): high-throughput screening for specific small molecule interactions with frozen tissue sections. AB - A novel screening system, using affinity imaging mass spectrometry (AIMS), has been developed to identify protein aggregates or organ structures in unfixed human tissue. Frozen tissue sections are positioned on small (millimetre-scale) stainless steel chips and incubated with an extensive library of small molecules. Candidate molecules showing specific affinity for the tissue section are identified by imaging mass spectrometry (IMS). As an example application, we screened over a thousand compounds against Alzheimer's disease (AD) brain tissue and identified several compounds with high affinity for AD brain sections containing tau deposits compared to age-matched controls. It should also be possible to use AIMS to isolate chemical compounds with affinity for tissue structures or components that have been extensively modified by events such as oxidation, phosphorylation, acetylation, aggregation, racemization or truncation, for example, due to aging. It may also be applicable to biomarker screening programs. PMID- 26365299 TI - Feasibility of Using Wideband Microwave System for Non-Invasive Detection and Monitoring of Pulmonary Oedema. AB - Pulmonary oedema is a common manifestation of various fatal diseases that can be caused by cardiac or non-cardiac syndromes. The accumulated fluid has a considerably higher dielectric constant compared to lungs' tissues, and can thus be detected using microwave techniques. Therefore, a non-invasive microwave system for the early detection of pulmonary oedema is presented. It employs a platform in the form of foam-based bed that contains two linear arrays of wideband antennas covering the band 0.7-1 GHz. The platform is designed such that during the tests, the subject lays on the bed with the back of the torso facing the antenna arrays. The antennas are controlled using a switching network that is connected to a compact network analyzer. A novel frequency-based imaging algorithm is used to process the recorded signals and generate an image of the torso showing any accumulated fluids in the lungs. The system is verified on an artificial torso phantom, and animal organs. As a feasibility study, preclinical tests are conducted on healthy subjects to determinate the type of obtained images, the statistics and threshold levels of their intensity to differentiate between healthy and unhealthy subjects. PMID- 26365300 TI - Pharmaceutical services cost analysis using time-driven activity-based costing: A contribution to improve community pharmacies' management. AB - BACKGROUND: The current financial crisis is pressing health systems to reduce costs while looking to improve service standards. In this context, the necessity to optimize health care systems management has become an imperative. However, little research has been conducted on health care and pharmaceutical services cost management. AIM: Pharmaceutical services optimization requires a comprehensive understanding of resources usage and its costs. This study explores the development of a time-driven activity-based costing (TDABC) model, with the objective of calculating the cost of pharmaceutical services to help inform policy-making. METHODS: Pharmaceutical services supply patterns were studied in three pharmacies during a weekday through an observational study. Details of each activity's execution were recorded, including time spent per activity performed by pharmacists. Data on pharmacy costs was obtained through pharmacies' accounting records. RESULTS: The calculated cost of a dispensing service in these pharmacies ranged from ?3.16 to ?4.29. The cost of a counseling service when no medicine was supplied ranged from ?1.24 to ?1.46. The cost of health screening services ranged from ?2.86 to ?4.55. CONCLUSION: The presented TDABC model gives us new insights on management and costs of community pharmacies. This study shows the importance of cost analysis for health care services, specifically on pharmaceutical services, in order to better inform pharmacies' management and the elaboration of pharmaceutical policies. PMID- 26365301 TI - Electrocardiac effects associated with lithium toxicity in children: an illustrative case and review of the pathophysiology. AB - Lithium is a potent psychotherapeutic agent that has gained wide acceptance in paediatrics, especially as adjunct treatment for severe behavioural, anxiety, and attention-deficit hyperactivity disorders, along with bipolar conditions. Its cardiac toxicity has been well-documented in adults; however, information is limited regarding lithium's effects on the heart in children. Therefore, paediatric cardiologists following-up children on lithium therapy should be cognizant of the cardiac side-effects and pathophysiology associated with this drug. In this manuscript, we used an illustrative case of a child who presented with lithium poisoning, in order to highlight adverse clinical manifestations that can arise from this medication. The cardiac cell membrane is thought to be the primary site of lithium's action. Thus, we reviewed lithium's effects on membrane electrogenic pumps and channels involved in the distribution and passage of sodium, potassium, and calcium across the sarcolemma, as these ions, and their associated currents, are the primary determinates of the action potentials underlying auto-rhythmicity and contractile activity of the heart. PMID- 26365302 TI - Molecular Assembly of Wheat Gliadins into Nanostructures: A Small-Angle X-ray Scattering Study of Gliadins in Distilled Water over a Wide Concentration Range. AB - Gliadin, one of the major proteins together with glutenin composing gluten, affects the physical properties of wheat flour dough. In this study, nanoscale structures of hydrated gliadins extracted into distilled water were investigated primarily by small-angle X-ray scattering (SAXS) over a wide range of concentrations. Gliadins are soluble in distilled water below 10 wt %. Guinier analyses of SAXS profiles indicate that gliadins are present as monomers together with small amounts of dimers and oligomers in a very dilute solution. The SAXS profiles also indicate that interparticle interference appears above 0.5 wt % because of electrostatic repulsion among gliadin assemblies. Above 15 wt %, gliadins form gel-like hydrated solids. At greater concentrations, a steep upturn appears in the low-q region owing to the formation of large aggregates, and a broad shoulder appears in the middle-q region showing density fluctuation inside. This study demonstrates that SAXS can effectively disclose the nanostructure of hydrated gliadin assemblies. PMID- 26365303 TI - Genetic variation in the oxytocin receptor gene is associated with a social phenotype in autism spectrum disorders. AB - Oxytocin regulates social behavior in animal models. Research supports an association between genetic variation in the oxytocin receptor gene (OXTR) and autism spectrum disorders (ASD). In this study, we examine the association between the OXTR gene and a specific social phenotype within ASD. This genotype phenotype investigation may provide insight into how OXTR conveys risk for social impairment. The current study investigated 10 SNPS in the OXTR gene that have been previously shown to be associated with ASD. We examine the association of these SNPs with both a social phenotype and a repetitive behavior phenotype comprised of behaviors commonly impaired in ASD in the Simons simplex collection (SSC). Using a large sample to examine the association between OXTR and ASD (n = range: 485-1002), we find evidence to support a relation between two OXTR SNPs and the examined social phenotype among children diagnosed with ASD. Greater impairment on the social responsiveness scale standardized total score and on several subdomains was observed among individuals with one or more copies of the minor frequency allele in both rs7632287 and rs237884. Linkage disequilibrium (LD) mapping suggests that these two SNPs are in LD within and overlapping the 3' untranslated region (3'-UTR) of the OXTR gene. These two SNPs were also associated with greater impairment on the repetitive behavior scale. Results of this study indicate that social impairment and repetitive behaviors in ASD are associated with genomic variation in the 3'UTR of the OXTR gene. These variants may be linked to an allele that alters stability of the mRNA message although further work is necessary to test this hypothesis. PMID- 26365304 TI - Unexpected formal insertion of CO2 into the C-Si bonds of a zinc compound. AB - Reaction of [kappa2-PR2C(SiMe3)Py]2Zn (R = Ph, 2a; iPr, 2b) with CO2 affords the products of formal insertion at the C-Si bond, [kappa2-PR2CC(O)O(SiMe3)Py]2Zn (R = Ph, 3a; iPr, 3b). Insertion product 3b was structurally characterized. The reaction appears to be a stepwise insertion and rearrangement of CO2 based on kinetic data. PMID- 26365305 TI - Insecticide exposure and farm history in relation to risk of lymphomas and leukemias in the Women's Health Initiative observational study cohort. AB - PURPOSE: Relationships of farm history and insecticide exposure at home or work with lymphohematopoietic (LH) neoplasm risk were investigated in a large prospective cohort of US women. METHODS: In questionnaires, women self-reported history living or working on a farm, personally mixing or applying insecticides, insecticide application in the home or workplace by a commercial service, and treating pets with insecticides. Relationships with non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, plasma cell neoplasms, and myeloid leukemia were investigated using Cox proportional hazard models. Age and farming history were explored as effect modifiers. RESULTS: The analysis included 76,493 women and 822 NHL cases. Women who ever lived or worked on a farm had 1.12 times the risk of NHL (95% confidence interval [CI] = 0.95-1.32) compared to those who did not. Women who reported that a commercial service ever applied insecticides in their immediate surroundings had 65% higher risk of CLL/SLL (95% CI = 1.15 2.38). Women aged less than 65 years who ever applied insecticides had 87% higher risk of DLBCL (95% CI = 1.13-3.09). CONCLUSIONS: Insecticide exposures may contribute to risk of CLL/SLL and DLBCL. Future studies should examine relationships of LH subtypes with specific types of household insecticides. PMID- 26365307 TI - One-step spray-coating process for the fabrication of colorful superhydrophobic coatings with excellent corrosion resistance. AB - A simple method was used to generate colorful hydrophobic stearate particles via chemical reactions between inorganic salts and sodium stearate. Colored self cleaning superhydrophobic coatings were prepared through a facile one-step spray coating process by spraying the stearate particle suspensions onto stainless steel substrates. Furthermore, the colorful superhydrophobic coating maintains excellent chemical stability under both harsh acidic and alkaline circumstances. After being immersed in a 3.5 wt % NaCl aqueous solution for 1 month, the as prepared coatings remained superhydrophobic; however, they lost their self cleaning property with a sliding angle of about 46 +/- 3 degrees . The corrosion behavior of the superhydrophobic coatings on the Al substrate was characterized by the polarization curve and electrochemical impedance spectroscopy (EIS). The electrochemical corrosion test results indicated that the superhydrophobic coatings possessed excellent corrosion resistance, which could supply efficient and long-term preservation for the bare Al substrate. PMID- 26365306 TI - Metalloprotease OMA1 Fine-tunes Mitochondrial Bioenergetic Function and Respiratory Supercomplex Stability. AB - Mitochondria are involved in key cellular functions including energy production, metabolic homeostasis, and apoptosis. Normal mitochondrial function is preserved by several interrelated mechanisms. One mechanism - intramitochondrial quality control (IMQC) - is represented by conserved proteases distributed across mitochondrial compartments. Many aspects and physiological roles of IMQC components remain unclear. Here, we show that the IMQC protease Oma1 is required for the stability of the respiratory supercomplexes and thus balanced and tunable bioenergetic function. Loss of Oma1 activity leads to a specific destabilization of respiratory supercomplexes and consequently to unbalanced respiration and progressive respiratory decline in yeast. Similarly, experiments in cultured Oma1 deficient mouse embryonic fibroblasts link together impeded supercomplex stability and inability to maintain proper respiration under conditions that require maximal bioenergetic output. Finally, transient knockdown of OMA1 in zebrafish leads to impeded bioenergetics and morphological defects of the heart and eyes. Together, our biochemical and genetic studies in yeast, zebrafish and mammalian cells identify a novel and conserved physiological role for Oma1 protease in fine-tuning of respiratory function. We suggest that this unexpected physiological role is important for cellular bioenergetic plasticity and may contribute to Oma1-associated disease phenotypes in humans. PMID- 26365308 TI - Advances in endoscopic imaging in ulcerative colitis. AB - Modern strategies for the treatment of ulcerative colitis require more accurate tools for gastrointestinal imaging to better assess mucosal disease activity and long-term prognostic clinical outcomes. Recent advances in gastrointestinal luminal endoscopy are radically changing the role of endoscopy in every-day clinical practice and research trials. Advanced endoscopic imaging techniques including high-definition endoscopes, optical magnification endoscopy, and various chromoendoscopy techniques have remarkably improved endoscopic assessment of ulcerative colitis. More recently, optical biopsy techniques with either endocytoscopy or confocal laser endomicroscopy have shown great potential in predicting several histological changes in real time during ongoing endoscopy. Here, we review current applications of advanced endoscopic imaging techniques in ulcerative colitis and present the most promising upcoming headways in this field. PMID- 26365309 TI - Lower esophageal sphincter pressures in patients of bronchial asthma and its correlation with spirometric parameters: a case-control study. AB - OBJECTIVES: The cause-effect relationship between bronchial asthma and gastro esophageal reflux (GER) is known, but studies have not been able to confirm the improvement of lung function with anti-acid therapy. Hypotensive lower esophageal sphincter (LES) may lead to both acid and non-acid reflux, resulting in asthma symptoms and decreased lung function. The objectives of our study were, firstly, to compare basal LES pressure between adult patients of asthma and normal controls and, secondly, to correlate the basal LES pressure with spirometric parameters in these patients. METHODS: Thirty patients, aged between 18 and 65 years, diagnosed as cases of bronchial asthma and 27 healthy controls were included in the study. All the participants were subjected to esophageal manometry after overnight fasting and basal LES pressures were recorded. Then, spirometry was done 2 h after meal and pre- and post-bronchodilator FEV1, FVC, PEFR were obtained for the asthma group. RESULTS AND CONCLUSIONS: There is significant difference between basal LES pressure in patients of bronchial asthma and control population (8.70 +/- 2.67 mmHg versus 16.64 +/- 5.52, p < 0.0001). 66.67% of the asthma patients have reduced LES pressures (<10 mmHg). The correlation coefficient between basal LES pressure and prebronchodilator FEV1% predicted is 0.596 (p < 0.0001, 95% CI 0.3002-0.7872). Obstructive airway impairment in adult patients of bronchial asthma is associated with hypotensive LES. GER, due to hypotensive LES may contribute to deterioration of spirometric parameters in asthma patients. PMID- 26365312 TI - Can Inexperienced Listeners Hear Who Is Flat? The Role of Timbre and Vibrato. AB - OBJECTIVES/HYPOTHESIS: Research has shown that the distribution of spectral energy and the presence of vibrato in a complex tone can affect pitch perception. This study sought to answer the questions: "Does timbre affect the perception of difference in pitch in complex synthetic stimuli modeled after singing voices?" "Does vibrato affect the perception of difference in pitch in complex synthetic stimuli modeled after singing voices?" and "Does the direction of timbre difference affect the perception of pitch difference?" STUDY DESIGN: This is a repeated-measures factorial design. METHODS: The experiment consisted of three experimental blocks at the pitches A3, G4, and F5, each with a vibrato and no vibrato subblock. For each block, two reference stimuli (mezzo-soprano and soprano) and six test stimuli (mezzo-soprano at frequencies of -1%, -2%, and -3%, soprano at frequencies of -1%, -2%, and -3%) were synthesized on the vowel /alpha/. Each reference stimulus was paired with itself, with the other reference stimulus, and with all the test stimuli. Vibrato stimuli had a rate of 5.6 Hz and a frequency vibrato extent of +/-50 cents. Listeners indicated the degree to which stimuli differed in pitch. RESULTS: Differences in timbre and vibrato were significant main effects on the perception of pitch difference. The direction of timbre difference was a consistent significant effect on the perception of pitch difference for the pitch G4; however, this was not a consistent effect at the pitches A3 and F5. CONCLUSION: Numerous factors can affect the perception of pitch including timbre and presence of vibrato. PMID- 26365311 TI - The Measurement of Airflow Using Singing Helmet That Allows Free Movement of the Jaw. AB - OBJECTIVES: Airflow measurement is a useful method of evaluating laryngeal physiology. We introduce a noninvasive device that measures airflow without restricting jaw movement or requiring phonation into a mouthpiece, thus facilitating measurement during singing and connected speech. STUDY DESIGN: Validation and human subject trials were conducted. Airflow measurements were obtained from 16 male and 16 female subjects during singing, speech, and constant vowel production tasks. METHODS: A similar helmet was designed by Stevens and Mead in 1968. The new device validity was evaluated by comparing the measured volume of air to a known volume of administered air using a calibration syringe. Subjects were asked to voice sustained vowels at low, medium, and high vocal intensity, read two sentences at a conversational volume, and perform different singing exercises while airflow was recorded. RESULTS: The device accurately and reliably measured airflow with mean airflow values falling within previously published ranges. There was an experimentally determined response time of 0.173 +/- 0.014 seconds. Subjects were able to comfortably perform speech and singing exercises. Male subjects had higher airflow for all sustained vowels (P < 0.05). Airflow was higher for abduction rather than adduction sentences (P < 0.05). CONCLUSIONS: No other portable device has been shown to measure airflow during singing and speech while allowing for free movement of the jaw. This device provides a more natural environment to measure airflow that could be used to help evaluate laryngeal function and aid in singing training. PMID- 26365310 TI - LRRK2 G2019S mutation attenuates microglial motility by inhibiting focal adhesion kinase. AB - In response to brain injury, microglia rapidly extend processes that isolate lesion sites and protect the brain from further injury. Here we report that microglia carrying a pathogenic mutation in the Parkinson's disease (PD) associated gene, G2019S-LRRK2 (GS-Tg microglia), show retarded ADP-induced motility and delayed isolation of injury, compared with non-Tg microglia. Conversely, LRRK2 knockdown microglia are highly motile compared with control cells. In our functional assays, LRRK2 binds to focal adhesion kinase (FAK) and phosphorylates its Thr-X-Arg/Lys (TXR/K) motif(s), eventually attenuating FAK activity marked by decreased pY397 phosphorylation (pY397). GS-LRRK2 decreases the levels of pY397 in the brain, microglia and HEK cells. In addition, treatment with an inhibitor of LRRK2 kinase restores pY397 levels, decreased pTXR levels and rescued motility of GS-Tg microglia. These results collectively suggest that G2019S mutation of LRRK2 may contribute to the development of PD by inhibiting microglial response to brain injury. PMID- 26365313 TI - A prospective cohort study of pulmonary function during pregnancy in women with and without asthma. AB - BACKGROUND AND OBJECTIVE: Pregnancy alters the severity of asthma unpredictably. Uncertainty still exists about longitudinal changes in pulmonary function during pregnancy in both healthy and asthmatic women. This study aimed to compare pulmonary function changes during pregnancy in healthy and asthmatic women and to determine the relationship between pulmonary function and asthma-related quality of life during pregnancy. A secondary aim was to investigate the application of forced expiratory volume in 6 s (FEV6) for monitoring asthma during pregnancy. METHODS: Pregnant women with (n = 20) and without asthma (n = 20) had pulmonary function tests at 8-20, 21-28 and 29-40 weeks gestation. Those with asthma also completed the Asthma Control Questionnaire (ACQ) and mini Asthma Quality of Life Questionnaire (mAQLQ) at each visit. RESULTS: Pulmonary function declined in both groups at follow-up #1 (more markedly in those with asthma) but then improved at follow-up #2 (more markedly in those with asthma). In those with asthma, ACQ scores increased, while mAQLQ scores declined at follow-up #1; whilst at follow up #2 these changes were in the opposite direction. FEV6 and forced vital capacity (FVC) were highly correlated (r = 0.88, p < 0.01) in asthmatics. CONCLUSIONS: Pulmonary function changes during second and third trimesters were more pronounced in asthmatics than in healthy women. FEV6 monitoring may assist pregnant women and their health professionals in optimizing asthma management. The changes in pulmonary function in women with asthma were not significantly associated with changes in asthma control or asthma-related quality of life. PMID- 26365314 TI - Evaluation of HS-SPME and ultrasonic solvent extraction for monitoring of plant flavours added by the bees to herbhoneys: traceability biomarkers. AB - The volatile composition of 21 herbhoneys (HHs) of 7 different botanical origins was characterised for the first time. Ultrasound solvent extraction (USE) and headspace solid-phase microextraction (HS-SPME) followed by GC-FID/MS were successfully applied as complementary methods for monitoring the volatile plant flavours added by the bees. HHs showed significant compositional variability related to the botanical origin and compounds that could serve as traceability biomarkers were identified. The most important compounds with high abundance were (E,extract; H, headspace): caffeine (up to 68.7%, E) and trans-linalool oxide (up to 26.0%, H) in coffee HH, alpha-terpineol (up to 8.2%, E; 27.1%, H) and bornyl acetate (up to 3.1, E; 11.9%, H) in pine HH, thymol (up to 3.1%, E; 55.4%, H) in thyme HH. Hawthorn HH was characterised by the presence of herniarin (up to 13.4%, E) and lemon HH contained limonene (up to 1.6%, E; 33.2%, H). Other HHs (nettle and aloe) contained lower amounts of volatiles and their profiles were not specific. In all the HHs, methyl syringate was found and it was most abundant in thyme HH (up to 17.4%, E). The volatile fraction of HHs showed some substantial similarities and differences with the composition of herbs from which they derive. It confirms the selective bee-mediated transfer of phytochemicals, including known flavour-active volatiles into the final product, but also biotransformation of several compounds. Additionally, several similarities to the corresponding natural honeys were observed, but in general HHs exhibited less rich volatile profiles. PMID- 26365315 TI - Response to 'Inclusion of Placebos and Blinding for Ascending Dose First-in-Human Studies and Other Underpowered Phase 1 studies has not been Justified and on Balance is Not Useful' by D.A. Parasrampuria and L.Z. Benet. PMID- 26365316 TI - Properties of theranostic nanoparticles determined in suspension by ultrasonic spectroscopy. AB - In the context of growing use of nanoparticles, it is important to be able to characterize all their physical properties in order to understand their behavior, to optimize them, and to control their quality. We showed that ultrasonic spectroscopy provides many of the desired properties. To do so, we used as an example nanocapsules made of a polymer shell encaspulating a liquid perfluorocarbon core and designed them for theranostic applications. Frequency dependent measurements of both ultrasound velocity and attenuation were performed on nanocapsule suspensions. Then the desired properties were extracted by analyzing the experimental data using a recently developed model that relates the speed of sound and attenuation of a suspension to the geometrical and viscoelastic properties of the nanocapsules. PMID- 26365317 TI - Enhanced anti-tumor efficacy and safety profile of tumor microenvironment responsive oncolytic adenovirus nanocomplex by systemic administration. AB - Oncolytic adenovirus (Ad) holds great promise as a potential gene therapy for cancer. However, intravenously administered Ad may encounter difficulties due to unfavorable host responses, non-specific interactions, and the heterogeneity of the tumor cell population. As an approach to combine the advantages of oncolytic Ad and synthetic polymers and to address the associated difficulties, Ad was physically complexed with a pH-sensitive block copolymer, methoxy poly(ethylene glycol)-b-poly(l-histidine) (mPEG-b-pHis). The in vitro transduction efficiency at an acidic extracellular pH was remarkably enhanced in cancer cells when treated with the Ad expressing green fluorescent protein (GFP) coated with mPEG-b pHis (c-dE1/GFP) as compared to that of naked Ad (n-dE1/GFP). Time-lapse total internal reflection fluorescence microscopic imaging revealed a significantly enhanced cellular uptake rate of c-dE1/GFP at acidic tumor pH when compared with that at neutral pH or naked cognate Ad (n-dE1/GFP). In addition, c-dE1/GFP remained relatively stable in human serum-containing media, and considerably reduced both the innate and adaptive immune response against Ad. Moreover, the therapeutic efficacy and survival benefit of mPEG-b-pHis-complexed oncolytic Ad (c-H5mT/Luc) by systemic treatment was significantly enhanced compared to that with naked oncolytic Ad (n-H5mT/Luc) in both coxsackie and adenovirus receptor positive and -negative tumors. Whole-body bioluminescence imaging showed 7.3-fold higher luciferase expression at the tumor site and 23.0-fold less luciferase expression in liver tissue for c-H5mT/Luc relative to that for naked oncolytic Ad (n-H5mT/Luc). Considering the heterogeneity of tumor tissue, these results are important for guiding the development of more potent and specific treatment of devastating metastatic cancers using this viral system. STATEMENT OF SIGNIFICANCE: Although adenoviral systems have shown considerable promise and undergone extensive evaluation attempts to specifically target Ad vectors to cancer cells have met limited success. This shortcoming is due to the strong immune response stimulated by Ad and the hepatotoxicity of the viral particles. To overcome restricted vector issues, we generated Ad/mPEG-b-pHis for tumor microenvironment-targeting hybrid vector systems, an oncolytic Ad coated with a pH-responsive polymer, mPEG-b-pHis. The Ad/mPEG-b-pHis exhibited pH-dependent transduction efficiency and cancer-cell killing effects. Moreover, systemic administration of oncolytic Ad/mPEG-b-pHis led to marked suppression of tumor growth and tumor-specific viral replication. Ad successfully avoided the innate and adaptive immune responses and liver accumulation with the help of mPEG-b-pHis on its surface. PMID- 26365318 TI - Aluminium leaching from red mud by filamentous fungi. AB - This contribution investigates the efficient and environmentally friendly aluminium leaching from red mud (bauxite residue) by 17 species of filamentous fungi. Bioleaching experiments were examined in batch cultures with the red mud in static, 7-day cultivation. The most efficient fungal strains in aluminium bioleaching were Penicillium crustosum G-140 and Aspergillus niger G-10. The A. niger G-10 strain was capable to extract up to approximately 141 mg.L(-1) of aluminium from 0.2 g dry weight red mud. Chemical leaching with organic acids mixture, prepared according to A. niger G-10 strain's respective fungal excretion during cultivation, proved that organic acids significantly contribute to aluminium solubilization from red mud. PMID- 26365319 TI - Tetracarboxylatoplatinum(IV) complexes featuring monodentate leaving groups - A rational approach toward exploiting the platinum(IV) prodrug strategy. AB - A series of novel symmetrically and unsymmetrically coordinated platinum(IV) complexes with monodentate carboxylato ligands was synthesized. The compounds exhibit a general coordination sphere of [Pt(en)(OCOR)2(OCOR')(OCOR")], where the carboxylato ligands are represented by acetato and succinic acid monoester ligands. Dicarboxylatoplatinum(II) complexes were synthesized and oxidized symmetrically or unsymmetrically to obtain platinum(IV) complexes, which were subsequently carboxylated with noncyclic anhydrides. The compounds were investigated in detail by elemental analysis, mass spectrometry, infrared and multinuclear ((1)H, (13)C, (15)N, (195)Pt) NMR spectroscopy as well as by X-ray diffraction in some cases. The reduction behavior was followed by NMR spectroscopy, while stability and lipophilicity were examined by analytical reversed phase HPLC measurements. Cytotoxic properties were studied in three human cancer cell lines derived from cisplatin sensitive ovarian teratocarcinoma (CH1/PA-1), cisplatin insensitive colon carcinoma (SW480) and non-small cell lung cancer (A549). Thereby, the most lipophilic (yet water soluble) platinum(IV) complexes showed promising IC50 values in the low micromolar and even nanomolar range, demonstrating the significant advantage of using equatorially coordinated monodentate carboxylato ligands. PMID- 26365320 TI - Effect of aluminium on migration of oestrogen unresponsive MDA-MB-231 human breast cancer cells in culture. AB - Aluminium (Al) has been measured in human breast tissue, and may be a contributory factor in breast cancer development. At the 10th Keele meeting, we reported that long-term exposure to Al could increase migratory properties of oestrogen-responsive MCF-7 human breast cancer cells suggesting a role for Al in the metastatic process. We now report that long-term exposure (20-25 weeks) to Al chloride or Al chlorohydrate at 10(-4) M or 10(-5) M concentrations can also increase the migration of oestrogen unresponsive MDA-MB-231 human breast cancer cells as measured using time-lapse microscopy and xCELLigence technology. In parallel, Al exposure was found to give rise to increased secretion of active matrix metalloproteinase MMP9 as measured by zymography, and increased intracellular levels of activated MMP14 as measured by western immunoblotting. These results demonstrate that Al can increase migration of human breast cancer cells irrespective of their oestrogen responsiveness, and implicate alterations to MMPs as a potential mechanism worthy of further study. PMID- 26365321 TI - Overexpression of Hif-1alpha in Mesenchymal Stem Cells Affects Cell-Autonomous Angiogenic and Osteogenic Parameters. AB - Reconstruction of large bone defects still represents a major medical challenge. In recent years tissue engineering has developed techniques based on adult mesenchymal stem cells (MSCs) that could represent an attractive therapeutical option to treat large bone defects in the future. It has been demonstrated in various animal models that ex vivo expanded MSCs are capable of promoting the regeneration of skeletal defects after implantation. However, for the efficient regeneration of bone in tissue engineering applications, a rapid vascularization of implanted grafts is essential to ensure the survival of cells in the early post-implantational phase. A promising strategy to enhance vascularization of MSC containing implants could consist of overexpression of the angiogenic master transcription factor Hypoxia-inducible factor 1 (Hif-1) in the MSCs in order to induce angiogenesis and support osteogenesis. In the present study, we overexpressed Hif-1alpha in MSCs by using recombinant adenoviruses and investigated cell-autonomous effects. Overexpression of Hif-1alpha enhanced proliferation, migration, cell survival and expression of pro-angiogenic genes. Other parameters such as expression of the osteogenic markers BMP-2 and RunX2 were decreased. Hif-1alpha overexpression had no effect on invasion, senescence and osteogenic differentiation of MSCs. Our experiments revealed multifarious effects of Hif-1alpha overexpression on cell-autonomous parameters. Therefore, Hif-1alpha overexpression may represent a therapeutic option to improve cellular functions of MSCs to treat critical sized bone defects. PMID- 26365322 TI - Functional profiling of adenylation domains in nonribosomal peptide synthetases by competitive activity-based protein profiling. AB - We describe competitive activity-based protein profiling (ABPP) to accelerate the functional prediction and assessment of adenylation (A) domains in nonribosomal peptide synthetases (NRPSs) in proteomic environments. Using a library of sulfamoyloxy-linked aminoacyl-AMP analogs, the competitive ABPP technique offers a simple and rapid assay system for adenylating enzymes and provides insight into enzyme substrate candidates and enzyme active-site architecture. PMID- 26365323 TI - Emergence of a novel prey life history promotes contemporary sympatric diversification in a top predator. AB - Intraspecific phenotypic variation can strongly impact community and ecosystem dynamics. Effects of intraspecific variation in keystone species have been shown to propagate down through the food web by altering the adaptive landscape for other species and creating a cascade of ecological and evolutionary change. However, similar bottom-up eco-evolutionary effects are poorly described. Here we show that life history diversification in a keystone prey species, the alewife (Alosa pseudoharengus), propagates up through the food web to promote phenotypic diversification in its native top predator, the chain pickerel (Esox niger), on contemporary timescales. The landlocking of alewife by human dam construction has repeatedly created a stable open water prey resource, novel to coastal lakes, that has promoted the parallel emergence of a habitat polymorphism in chain pickerel. Understanding how strong interactions propagate through food webs to influence diversification across multiple trophic levels is critical to understand eco-evolutionary interactions in complex natural ecosystems. PMID- 26365324 TI - Spontaneous perforation of pyometra presenting as acute abdomen: a rare condition with considerable mortality. AB - Pyometra is an uncommon and potentially lethal disease that occurs mainly in postmenopausal women. Spontaneous perforation of pyometra presenting as acute abdomen is an extremely rare complication of pyometra, and the patients are always admitted to the emergency department. An additional case is reported herein. In addition, a literature review was performed between 1949 and 2015. A correct preoperative diagnosis was made in 21.05% of all the cases. Of all cases, 25.71% were associated with malignant disease. The mortality rate of spontaneous perforation of pyometra is 31.88%. Thus, it should be considered in the differential diagnosis of acute abdomen in elderly women. Total hysterectomy along with bilateral salpingo-oophorectomy is the preferred treatment. Administration of broad-spectrum antibiotics and postoperative intensive care support are essential to reduce the high mortality. PMID- 26365325 TI - N-Heterocyclic Carbene-Phosphinidene Complexes of the Coinage Metals. AB - Coinage metal complexes of the N-heterocyclic carbene-phosphinidene adduct IPr?PPh (IPr=1,3-bis(2,6-diisopropylphenyl)imidazolin-2-ylidene) were prepared by its reaction with CuCl, AgCl, and [(Me2 S)AuCl], which afforded the monometallic complexes [(IPr?PPh)MCl] (M=Cu, Ag, Au). The reaction with two equivalents of the metal halides gave bimetallic [(IPr?PPh)(MCl)2 ] (M=Cu, Au); the corresponding disilver complex could not be isolated. [(IPr?PPh)(CuOTf)2 ] was prepared by reaction with copper(I) trifluoromethanesulfonate. Treatment of [(IPr?PPh)(MCl)2 ] (M=Cu, Au) with Na(BAr(F) ) or AgSbF6 afforded the tetranuclear complexes [(IPr?PPh)2 M4 Cl2 ]X2 (X=BAr(F) or SbF6 ), which contain unusual eight-membered M4 Cl2 P2 rings with short cuprophilic or aurophilic contacts along the chlorine bridged M???M axes. Complete chloride abstraction from [(IPr?PPh)(AuCl)2 ] was achieved with two equivalents of AgSbF6 in the presence of tetrahydrothiophene (THT) to form [(IPr?PPh){Au(THT)}2 ][SbF6 ]2 . The cationic tetra- and dinuclear complexes were used as catalysts for enyne cyclization and carbene transfer reactions. PMID- 26365327 TI - Diagenetic Evolution and Reservoir Quality of Sandstones in the North Alpine Foreland Basin: A Microscale Approach. AB - Siliciclastic reservoir rocks of the North Alpine Foreland Basin were studied focusing on investigations of pore fillings. Conventional oil and gas production requires certain thresholds of porosity and permeability. These parameters are controlled by the size and shape of grains and diagenetic processes like compaction, dissolution, and precipitation of mineral phases. In an attempt to estimate the impact of these factors, conventional microscopy, high resolution scanning electron microscopy, and wavelength dispersive element mapping were applied. Rock types were established accordingly, considering Poro/Perm data. Reservoir properties in shallow marine Cenomanian sandstones are mainly controlled by the degree of diagenetic calcite precipitation, Turonian rocks are characterized by reduced permeability, even for weakly cemented layers, due to higher matrix content as a result of lower depositional energy. Eocene subarkoses tend to be coarse-grained with minor matrix content as a result of their fluvio deltaic and coastal deposition. Reservoir quality is therefore controlled by diagenetic clay and minor calcite cementation.Although Eocene rocks are often matrix free, occasionally a clay mineral matrix may be present and influence cementation of pores during early diagenesis. Oligo-/Miocene deep marine rocks exhibit excellent quality in cases when early cement is dissolved and not replaced by secondary calcite, mainly bound to the gas-water contact within hydrocarbon reservoirs. PMID- 26365326 TI - Menopausal estrogen therapy and non-Hodgkin's lymphoma: A post-hoc analysis of women's health initiative randomized clinical trial. AB - Estrogens are important immunomodulators, exerting significant effects on cell proliferation, apoptosis, cytokine production and differentiation of hematopoietic cells. Estrogen receptors are expressed on normal B and T lymphocytes, bone marrow and in leukemia and lymphoma cell lines. Epidemiologic evidence for the association of menopausal hormone use with risk of non-Hodgkin's lymphoma (NHL) has been mixed; however, all of the investigations have been observational. We analyzed the data from Women's Health Initiative hormone therapy trials where conjugated equine estrogens (CEE; 0.625 mg/d) plus medroxyprogesterone acetate (MPA; 2.5 mg/d) (n = 16,654) or CEE alone (women with prior hysterectomy) (n = 10,685) were tested against placebos and the intervention lasted a median of 5.6 years in the CEE + MPA trial and 7.2 years in the CEE alone trial. During 13 years of follow-up through September 20, 2013 383 incident NHL cases were identified. We used the intent-to-treat approach to calculate incidence rates of NHL, hazards ratios (HR) and 95% confidence intervals (CI) by treatment group. Incidence of NHL was virtually the same in the treatment and placebo groups. The HR was 1.02 (95%CI 0.74-1.39) for CEE alone, 0.98 (95% CI 0.76-1.28) for CEE+MPA, and 1.00 (95% CI 0.82-1.22) for both combined. There were no specific NHL subtypes associated with either type of the treatment, except a marginally decreased risk of plasma cell neoplasms (HR= 0.53 95% CI 0.27-1.03) in the CEE-alone group. These results do not support a role of estrogen alone or combined with progestin in the development of NHL among postmenopausal women. PMID- 26365328 TI - Renegotiating hope while living with lymphoedema after cancer: a qualitative study. AB - Hope is defined as a multi-dimensional life force, a coping resource and a necessity for coping with illness. Concepts of normalcy, hope and loss are explored in this qualitative study and positioned within recent scholarship on hope in cancer survivors. The experiences of 13 participants (11 women, 2 men) in two Canadian provinces who were living with lymphoedema secondary to cancer were analysed. For these participants, hope assumed various meanings. For some, hope was seen as passive inaction, whereas hope for others was positive and action oriented, even when faced with the uncertainty of chronic illness. Hope for the individual with lymphoedema is also juxtaposed with hope associated with cancer treatment where a desired return to normal is the object of hope and paramount to coping. However, when met with the chronic nature of lymphoedema, the hope of a return to normalcy is lost and the meaning, direction and actions of hope must be renegotiated. PMID- 26365329 TI - Optimal design of compact and connected nature reserves for multiple species. AB - When designing a conservation reserve system for multiple species, spatial attributes of the reserves must be taken into account at species level. The existing optimal reserve design literature considers either one spatial attribute or when multiple attributes are considered the analysis is restricted only to one species. We built a linear integer programing model that incorporates compactness and connectivity of the landscape reserved for multiple species. The model identifies multiple reserves that each serve a subset of target species with a specified coverage probability threshold to ensure the species' long-term survival in the reserve, and each target species is covered (protected) with another probability threshold at the reserve system level. We modeled compactness by minimizing the total distance between selected sites and central sites, and we modeled connectivity of a selected site to its designated central site by selecting at least one of its adjacent sites that has a nearer distance to the central site. We considered structural distance and functional distances that incorporated site quality between sites. We tested the model using randomly generated data on 2 species, one ground species that required structural connectivity and the other an avian species that required functional connectivity. We applied the model to 10 bird species listed as endangered by the state of Illinois (U.S.A.). Spatial coherence and selection cost of the reserves differed substantially depending on the weights assigned to these 2 criteria. The model can be used to design a reserve system for multiple species, especially species whose habitats are far apart in which case multiple disjunct but compact and connected reserves are advantageous. The model can be modified to increase or decrease the distance between reserves to reduce or promote population connectivity. PMID- 26365330 TI - The effect of zinc supplementation on pregnancy outcome: a randomized controlled trial. AB - OBJECTIVES: This study aimed to evaluate the impact of prenatal zinc supplementation on pregnancy outcomes. METHODS: A randomized controlled trial with equal randomization (1:1) was conducted on 540 pregnant women in Rasht, Iran from January 2010 to January 2012. Participants were randomly assigned to receive a daily supplement including 400-ug folic acid and 30-mg ferrous sulfate, with or without 15-mg zinc sulfate from the 16th week of gestation until delivery. RESULTS: Mean difference of birth weight between the two groups was not significantly different (3262 +/- 390 g in the zinc, 3272 +/- 403 g in the no zinc groups) (p = 0.780). There were no significant differences between the two groups in terms of means of head circumference (p = 0.999), length (p = 0.848), and gestational age at birth (p = 0.057) incidences of low birth weight (p = 0.863), macrosomia (p = 0.642), and the Apgar score >7 at 5 min (p = 0.999), incidences of preterm delivery (p = 0.999), pre-eclampsia (p = 0.835), premature rupture of membranes (p = 0.630), and spontaneous abortion (p = 0.772). Abruption of placenta, amnionitis, stillbirth, and intrauterine death were not observed. CONCLUSION: Based on our findings, 15-mg zinc supplementation daily from 16 weeks of pregnancy until delivery cannot improve pregnancy outcomes. PMID- 26365332 TI - Custom fit 3D-printed brain holders for comparison of histology with MRI in marmosets. AB - BACKGROUND: MRI has the advantage of sampling large areas of tissue and locating areas of interest in 3D space in both living and ex vivo systems, whereas histology has the ability to examine thin slices of ex vivo tissue with high detail and specificity. Although both are valuable tools, it is currently difficult to make high-precision comparisons between MRI and histology due to large differences inherent to the techniques. A method combining the advantages would be an asset to understanding the pathological correlates of MRI. NEW METHOD: 3D-printed brain holders were used to maintain marmoset brains in the same orientation during acquisition of ex vivo MRI and pathologic cutting of the tissue. RESULTS: The results of maintaining this same orientation show that sub millimeter, discrete neuropathological features in marmoset brain consistently share size, shape, and location between histology and ex vivo MRI, which facilitates comparison with serial imaging acquired in vivo. COMPARISON WITH EXISTING METHODS: Existing methods use computational approaches sensitive to data input in order to warp histologic images to match large-scale features on MRI, but the new method requires no warping of images, due to a preregistration accomplished in the technique, and is insensitive to data formatting and artifacts in both MRI and histology. CONCLUSIONS: The simple method of using 3D printed brain holders to match brain orientation during pathologic sectioning and MRI acquisition enables rapid and precise comparison of small features seen on MRI to their underlying histology. PMID- 26365333 TI - Consistent and reproducible staining of glia by a modified Golgi-Cox method. AB - BACKGROUND: Golgi-Cox staining is a powerful histochemical approach which has been used extensively to visualize the morphology of neurons and glia. However, its usage as a first-choice method is hindered by its uncertain nature, diminished consistency and lengthy staining duration. The FD Rapid GolgiStainTM Kit (FD Neurotechnologies, Inc., USA) has been developed by employing the Golgi Cox approach. It is a simple, reliable and reproducible way of performing Golgi impregnation for the analysis of neuronal morphology. NEW METHOD: We report here simple modifications to the manufacturer's protocol which enable reproducible and reliable staining of glial cells. RESULTS: Exposure of brain tissue to 4% paraformaldehyde (PFA) during perfusion followed by postfixation with 8% glutaraldehyde in 4% PFA led to only glial cells being stained, whereas in the absence of postfixation both neurons and glia were stained with unclear morphology. Additionally, we found that impregnation at 26 degrees C+/-1 was critical to attain uniform staining. COMPARISON WITH EXISTING METHOD: Our modified Golgi-Cox approach is consistent and reproducible and affords uniform glial staining throughout the brain. CONCLUSION: As this protocol stains only a small percentage of cells, it is suitable for the analysis of individual cells. PMID- 26365331 TI - The effect of early-life stress and chronic high-sucrose diet on metabolic outcomes in female rats. AB - Early-life stress affects metabolic outcomes and choice of diet influences the development of metabolic disease. Here we tested the hypothesis that chronic sugar intake exacerbates metabolic deficits induced by early-life stress. Early life stress was induced in Sprague-Dawley rats using limited nesting material in early lactation (LN, postnatal days 2-9), and siblings were given chow alone or with additional sucrose post weaning (n = 9-17 per group). Female control and LN siblings had unlimited access to either chow plus water, or chow and water plus 25% sucrose solution (Sucrose), from 3-15 weeks of age. Weekly body weight and food intake were measured. Glucose and insulin tolerance were tested at 13 and 14 weeks of age, respectively. Rats were killed at 15 weeks. Hepatic triglyceride and markers of lipid synthesis - fatty acid synthase, acetyl-CoA carboxylase alpha and oxidation - and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (Pgc-1alpha) were examined. Mediators of hepatic glucocorticoid metabolism, specifically 11-beta hydroxysteroid dehydrogenase-1 (11betaHSD-1), 5-alpha reductase, and glucocorticoid and mineralocorticoid receptor mRNAs were also measured. Sucrose increased caloric intake in both groups, but overall energy intake was not altered by LN exposure. LN exposure had no further impact on sucrose-induced glucose intolerance and increased plasma and liver triglycerides. Hepatic markers of fat synthesis and oxidation were concomitantly activated and 11betaHSD-1 mRNA expression was increased by 53% in LN-Sucrose versus Con-Sucrose rats. Adiposity was increased by 26% in LN-Sucrose versus Con-Sucrose rats. Thus, LN exposure had minimal adverse metabolic effects despite high-sugar diet postweaning. PMID- 26365335 TI - Investigation of a potential pharmacokinetic interaction between perindopril arginine and amlodipine when administered as a single perindopril/amlodipine fixed-dose combination tablet in healthy Chinese male volunteers. AB - OBJECTIVES: To determine whether a potential pharmacokinetic interaction exists between perindopril arginine 5 mg and amlodipine 5 mg, after administration as a fixed-combination of perindopril 5 mg/amlodipine 5 mg (S05985). METHODS: A total of 30 subjects was enrolled into this single center, open-label, randomized, 3 period cross-over study and was randomized to receive 1 tablet of S05985, 1 tablet of perindopril tert-butylamine 4 mg, or 1 tablet of amlodipine 5 mg. The doses of both perindopril salts correspond to 3.34 mg of perindopril expressed as free acid. Serial blood samples were collected in each treatment period for determination of plasma amlodipine, perindopril, and perindoprilat concentrations and for calculation of the respective pharmacokinetic parameters (AUC(0 infinity), AUC(0-t), C(max), and t(max)). Statistical analyses of the pharmacokinetic parameters included ANOVA and calculations of 90% confidence intervals for the ratio of the geometric means for Cmax, AUC(0-t), and AUC(0 infinity). Safety was also assessed. RESULTS: A total of 29 subjects completed the study per protocol. There was no serious adverse event. All 90% confidence intervals for C(max), AUC(0-t), and AUC(0-infinity) for perindopril, perindoprilat, and amlodipine were within the limits (80.00 - 125%), indicating that both treatments were bioequivalent. CONCLUSION: These results indicate that no drug-drug interaction exists after single-dose oral administration of S05985 (perindopril 5 mg and amlodipine 5 mg) when compared to single-dose administration of each component alone, i.e., perindopril tert-butylamine 4 mg and amlodipine 5 mg, given separately. PMID- 26365334 TI - So you think you can jump? A novel long jump assessment to detect deficits in stroked mice. AB - BACKGROUND: Stroke survivors suffer from persistent disability, as well as severe sensorimotor and cognitive deficits. The preclinical assessment of such deficits is important for the development of novel interventions and therapeutics. NEW METHOD: The aim of this study was to develop a quantitative behavioral measure of hindlimb functionality in rodents, which could be used to assess deficits after a neural injury, such as stroke. Here we introduce a test to measure long jump behavior in mice. RESULTS: Using this test we first showed that while male and female mice exhibited no differences in jump success rate, the female mice showed lower baseline jumping latencies. Next we demonstrated that the induction of a cerebral stroke via middle cerebral artery occlusion (MCAO) for 45min did not affect the jump success rate in either group; however, it did significantly increase jump latencies in both male and female mice. Finally, we used therapeutic interventions to explore mechanisms that may be involved in producing this increase in jump latency by administering the anti-depressant fluoxetine prior to the long jump assay, and also tested for potential changes in anxiety levels after stroke. COMPARISON WITH EXISTING METHODS: Other methods to assess hindlimb functionality are not specific, because they measure behaviors that rely not only on hindlimbs, but also on forelimbs and tail. CONCLUSIONS: This study introduces a novel assay that can be used to measure a stroke induced behavioral deficit with great sensitivity, and raises interesting questions about potential mechanisms regulating this effect. PMID- 26365336 TI - Factors affecting intrasubject variability of PK exposure: absolute oral bioavailability and acidic nature of drugs. AB - OBJECTIVES: The aim of the present study is to investigate factors affecting intrasubject variability of pharmacokinetic (PK) exposure, which affect the results of bioequivalence (BE) studies. We focused on two factors: absolute oral bioavailability (BA) and acidic nature of drugs. METHODS: Intrasubject coefficient of variation (CV) for Cmax and AUC was estimated based on the 90% confidence intervals (CIs) and the number of subjects from fasting BE study results for our investigation. Relationships between the intrasubject CV and the absolute oral BA as well as the acidic nature of the drugs were investigated. RESULTS: First, the relationship between absolute oral BA and intrasubject variability of PK exposure (Cmax and AUC) showed negative log-linear relationship in the BE studies following oral administration of 65 immediate-release drugs under fasted condition. Drugs with poor absolute oral BA of less than 5% showed high intrasubject CV in the range of 30-65%. In contrast, drugs with high absolute oral BA of more than 80% showed low intrasubject CV of less than 20%. Second, acidic drugs with pKa<6 had higher intrasubject CV of Cmax than AUC compared to other types of drugs. The intrasubject CV ratios of Cmax to AUC for acidic drugs with pKa<6 were significantly higher than those for other types of drugs. CONCLUSION: Results show that absolute oral BA is one of the major factors that predict the extent of intrasubject variability of PK exposure. Acidic nature of drugs is thought to be an additional factor increasing intrasubject variability of Cmax as compared to AUC. PMID- 26365337 TI - Effect of liraglutide vs. NPH in combination with metformin on blood glucose fluctuations assessed using continuous glucose monitoring in patients with newly diagnosed type 2 diabetes. AB - BACKGROUND: To evaluate the effect of liraglutide and NPH on blood glucose fluctuations in patients with newly diagnosed type 2 diabetes mellitus (T2DM). METHODS: A total of 63 newly diagnosed T2DM patients were randomized into a liraglutide group and an NPH group. They were treated for 12 weeks. The values of CGM, HbA1C, and BMI were measured and compared before and after treatment. RESULTS: FPG, HbAlc, and MBG were decreased in both groups after 12 weeks of treatment. In the liraglutide group, the MAGE, SDBG, LAGE, BMI, and waist circumference were significantly 1ower than in the NPH group (p<0.05). Patients in the liraglutide group had a greater incidence of gastrointestinal adverse effects than in the NPH group (p<0.05). The incidence of hypoglycemia episode in the liraglutide group was significantly lower than in the NPH group (p<0.05). CONCLUSIONS: Liraglutide achieved improvements in overall glycemic control similar to NPH in patients with newly diagnosed T2DM. Liraglutide was associated with less glucose fluctuation than NPH treatment as assessed by CGM. In addition, patients in the liraglutide group had a greater incidence of gastrointestinal adverse effects, a lower incidence of hypoglycemia, and some weight reduction. PMID- 26365338 TI - Penetrance of Hemochromatosis in HFE Genotypes Resulting in p.Cys282Tyr and p.[Cys282Tyr];[His63Asp] in the eMERGE Network. AB - Hereditary hemochromatosis (HH) is a common autosomal-recessive disorder associated with pathogenic HFE variants, most commonly those resulting in p.Cys282Tyr and p.His63Asp. Recommendations on returning incidental findings of HFE variants in individuals undergoing genome-scale sequencing should be informed by penetrance estimates of HH in unselected samples. We used the eMERGE Network, a multicenter cohort with genotype data linked to electronic medical records, to estimate the diagnostic rate and clinical penetrance of HH in 98 individuals homozygous for the variant coding for HFE p.Cys282Tyr and 397 compound heterozygotes with variants resulting in p.[His63Asp];[Cys282Tyr]. The diagnostic rate of HH in males was 24.4% for p.Cys282Tyr homozygotes and 3.5% for compound heterozygotes (p < 0.001); in females, it was 14.0% for p.Cys282Tyr homozygotes and 2.3% for compound heterozygotes (p < 0.001). Only males showed differences across genotypes in transferrin saturation levels (100% of homozygotes versus 37.5% of compound heterozygotes with transferrin saturation > 50%; p = 0.003), serum ferritin levels (77.8% versus 33.3% with serum ferritin > 300 ng/ml; p = 0.006), and diabetes (44.7% versus 28.0%; p = 0.03). No differences were found in the prevalence of heart disease, arthritis, or liver disease, except for the rate of liver biopsy (10.9% versus 1.8% [p = 0.013] in males; 9.1% versus 2% [p = 0.035] in females). Given the higher rate of HH diagnosis than in prior studies, the high penetrance of iron overload, and the frequency of at-risk genotypes, in addition to other suggested actionable adult-onset genetic conditions, opportunistic screening should be considered for p.[Cys282Tyr];[Cys282Tyr] individuals with existing genomic data. PMID- 26365340 TI - Truncating Mutations of MAGEL2, a Gene within the Prader-Willi Locus, Are Responsible for Severe Arthrogryposis. AB - Arthrogryposis multiplex congenita (AMC) is characterized by the presence of multiple joint contractures resulting from reduced or absent fetal movement. Here, we report two unrelated families affected by lethal AMC. By genetic mapping and whole-exome sequencing in a multiplex family, a heterozygous truncating MAGEL2 mutation leading to frameshift and a premature stop codon (c.1996delC, p.Gln666Serfs*36) and inherited from the father was identified in the probands. In another family, a distinct heterozygous truncating mutation leading to frameshift (c.2118delT, p.Leu708Trpfs*7) and occurring de novo on the paternal allele of MAGEL2 was identified in the affected individual. In both families, RNA analysis identified the mutated paternal MAGEL2 transcripts only in affected individuals. MAGEL2 is one of the paternally expressed genes within the Prader Willi syndrome (PWS) locus. PWS is associated with, to varying extents, reduced fetal mobility, severe infantile hypotonia, childhood-onset obesity, hypogonadism, and intellectual disability. MAGEL2 mutations have been recently reported in affected individuals with features resembling PWS and called Schaaf Yang syndrome. Here, we show that paternal MAGEL2 mutations are also responsible for lethal AMC, recapitulating the clinical spectrum of PWS and suggesting that MAGEL2 is a PWS-determining gene. PMID- 26365339 TI - Genetic Defects in TAPT1 Disrupt Ciliogenesis and Cause a Complex Lethal Osteochondrodysplasia. AB - The evolutionarily conserved transmembrane anterior posterior transformation 1 protein, encoded by TAPT1, is involved in murine axial skeletal patterning, but its cellular function remains unknown. Our study demonstrates that TAPT1 mutations underlie a complex congenital syndrome, showing clinical overlap between lethal skeletal dysplasias and ciliopathies. This syndrome is characterized by fetal lethality, severe hypomineralization of the entire skeleton and intra-uterine fractures, and multiple congenital developmental anomalies affecting the brain, lungs, and kidneys. We establish that wild-type TAPT1 localizes to the centrosome and/or ciliary basal body, whereas defective TAPT1 mislocalizes to the cytoplasm and disrupts Golgi morphology and trafficking and normal primary cilium formation. Knockdown of tapt1b in zebrafish induces severe craniofacial cartilage malformations and delayed ossification, which is shown to be associated with aberrant differentiation of cranial neural crest cells. PMID- 26365342 TI - Scaffold protein enigma homolog activates CREB whereas a short splice variant prevents CREB activation in cardiomyocytes. AB - Enigma Homolog (ENH1 or Pdlim5) is a scaffold protein composed of an N-terminal PDZ domain and three LIM domains at the C-terminal end. The enh gene encodes for several splice variants with opposing functions. ENH1 promotes cardiomyocytes hypertrophy whereas ENH splice variants lacking LIM domains prevent it. ENH1 interacts with various Protein Kinase C (PKC) isozymes and Protein Kinase D1 (PKD1). In addition, the binding of ENH1's LIM domains to PKC is sufficient to activate the kinase without stimulation. The downstream events of the ENH1 PKC/PKD1 complex remain unknown. PKC and PKD1 are known to phosphorylate the transcription factor cAMP-response element binding protein (CREB). We tested whether ENH1 could play a role in the activation of CREB. We found that, in neonatal rat ventricular cardiomyocytes, ENH1 interacts with CREB, is necessary for the phosphorylation of CREB at ser133, and the activation of CREB-dependent transcription. On the contrary, the overexpression of ENH3, a LIM-less splice variant, inhibited the phosphorylation of CREB. ENH3 overexpression or shRNA knockdown of ENH1 prevented the CREB-dependent transcription. Our results thus suggest that ENH1 plays an essential role in CREB's activation and dependent transcription in cardiomyocytes. At the opposite, ENH3 prevents the CREB transcriptional activity. In conclusion, these results provide a first molecular explanation to the opposing functions of ENH splice variants. PMID- 26365341 TI - Identification of a Recognizable Progressive Skeletal Dysplasia Caused by RSPRY1 Mutations. AB - Skeletal dysplasias are highly variable Mendelian phenotypes. Molecular diagnosis of skeletal dysplasias is complicated by their extreme clinical and genetic heterogeneity. We describe a clinically recognizable autosomal-recessive disorder in four affected siblings from a consanguineous Saudi family, comprising progressive spondyloepimetaphyseal dysplasia, short stature, facial dysmorphism, short fourth metatarsals, and intellectual disability. Combined autozygome/exome analysis identified a homozygous frameshift mutation in RSPRY1 with resulting nonsense-mediated decay. Using a gene-centric "matchmaking" system, we were able to identify a Peruvian simplex case subject whose phenotype is strikingly similar to the original Saudi family and whose exome sequencing had revealed a likely pathogenic homozygous missense variant in the same gene. RSPRY1 encodes a hypothetical RING and SPRY domain-containing protein of unknown physiological function. However, we detect strong RSPRY1 protein localization in murine embryonic osteoblasts and periosteal cells during primary endochondral ossification, consistent with a role in bone development. This study highlights the role of gene-centric matchmaking tools to establish causal links to genes, especially for rare or previously undescribed clinical entities. PMID- 26365343 TI - An 8 minute colorimetric paper-based reverse phase vertical flow serum microarray for screening of hyper IgE syndrome. AB - Reverse phase microarrays are useful tools for affinity-based detection in hundreds of samples simultaneously. However, current methods typically require long assay times and fluorescent detection. Here we describe a paper-based Vertical Flow Microarray (VFM) assay as a rapid 8-minute colorimetric alternative for reverse phase microarray analysis. The VFM platform was optimized for detection of IgE with a detection limit of 1.9 MUg mL(-1) in whole serum. Optimized conditions were then used to screen 113 serum samples simultaneously for hyper IgE syndrome (hIgE), a rare primary immunodeficiency characterized by elevated levels of IgE. The same set of samples were then analysed with a conventional planar microarray with fluorescent detection for head-to-head testing. Both assays found elevated levels in three out of four hIgE patient samples, whereas no control samples displayed elevated levels in either method. The comparison experiments showed a good correlation between the two assays, as determined from a linear correlation study (Pearson's r = 0.76). Further, the assay-time reduction and reproducibility (intra assay CV = 12.4 +/- 4.11%) demonstrate the applicability of the VFM platform for high throughput reverse phase screening. PMID- 26365344 TI - The first complete mitochondrial genome of the Pundamilia nyererei. AB - Pundamilia nyererei, a member of the family cichlid lived in individual African lakes, regarded as a significant evolution model. Recently the genome sequencing had been done, but no more information of its mitochondrial reported. Herein, we first assembled the complete mitochondrial genome sequence of Pundamilia nyererei. It is a 16 758 bp long sequence with most mitogenome's characteristic structure, 13 protein-coding genes, 20 of tRNA genes, two of rRNA genes, and one putative control region. The GC-content of our fresh sequence is 45.24%, similar to closely related species Oreochromis niloticus. It can verify the accuracy and the utility of new determined mitogenome sequences by the phylogenetic analysis, based on whole mitogenome alignment with Dimidiochromis compressiceps, which is closest relative to Pundamilia nyererei, and seven others. We expect that using the full mitogenome to address taxonomic issues and study the related evolution events. Moreover, this is the first report of the mitogenome of genus Pundamilia nyererei. PMID- 26365345 TI - Amphiregulin may be a new biomarker of classically activated macrophages. AB - Amphiregulin (Areg) participates in tissue repair and inflammation regulation. As important effector cells in inflammation, macrophages can be polarized to classically (M1) or alternatively (M2) activated phenotype with diverse functions in immunity. However, the relationship between Areg expression and macrophage activation is poorly understood. Here we report that Areg was significantly expressed in M1 but not in M2 macrophages. This was confirmed by analyses of RT PCR and ELISA in peritoneal macrophages, and by evaluating protein expression in alveolar macrophages and RAW264.7 cells. Selective inhibitors of TLR4 (CLI-095) and MAP kinase, including Erk1/2 (PD98059), JNK (SP600125) and p38 (SB203580), significantly reduced Areg expression in M1 macrophages, suggesting that M1 macrophages produce Areg mainly through the TLR4-MAPK pathway, which is involved in the mechanism of M1 activation. When compared with productions of classical biomarkers of M1 macrophages, Areg expression was highly consistent in time series. Taken together, Areg may be an effective new biomarker of M1 macrophages. PMID- 26365346 TI - Deinococcus radiodurans RecA nucleoprotein filaments characterized at the single molecule level with optical tweezers. AB - Deinococcus radiodurans can survive extreme doses of ionizing radiation due to the very efficient DNA repair mechanisms that are able to cope even with hundreds of double-strand breaks. RecA, the critical protein of homologous recombination in bacteria, is one of the key components of the DNA-repair system. Repair of double-strand breaks requires RecA binding to DNA and assembly of the RecA nucleoprotein helical filaments. The Escherichia coli RecA protein (EcRecA) and its interactions with DNA have been extensively studied using various approaches including single-molecule techniques, while the D. radiodurans RecA (DrRecA) remains much less characterized. However, DrRecA shows some remarkable differences from E. coli homolog. Here we combine microfluidics and single molecule DNA manipulation with optical tweezers to follow the binding of DrRecA to long double-stranded DNA molecules and probe the mechanical properties of DrRecA nucleoprotein filaments at physiological pH. Our data provide a direct comparison of DrRecA and EcRecA binding to double-stranded DNA under identical conditions. We report a significantly faster filaments assembly as well as lower values of persistence length and contour length for DrRecA nucleoprotein filaments compared to EcRecA. Our results support the existing model of DrRecA forming more frequent and less continuous filaments relative to those of EcRecA. PMID- 26365347 TI - N-Oleoyl glycine, a lipoamino acid, stimulates adipogenesis associated with activation of CB1 receptor and Akt signaling pathway in 3T3-L1 adipocyte. AB - Adipose tissue plays a vital role in the development of obesity and related diseases. The aim of the present study was to investigate the effects of N-Oleoyl glycine (OLGly), a lipoamino acid, on 3T3-L1 adipogenesis and to explore the likely mechanisms underlying this process. Lipid accumulation were evaluated using Oil Red O staining and triglyceride content assay. The mRNA expressions of cannabinoid receptors and the protein expressions of adipogenic genes and intracellular signaling pathway were determined by real-time quantitative PCR and western blot, respectively. The results indicated that OLGly itself, but not its degradation products, stimulated lipid accumulation and significantly increased adipogenic genes (PPARgamma and aP2), in a dose- and time-dependent manner. Additionally, OLGly markedly increased the mRNA expression of CB1 receptor (CB1R) and the inhibition of CB1R by its antagonist SR141716 abolished the promotive effects of OLGly on lipid accumulation and the protein expression of PPARgamma and aP2. Furthermore, OLGly increased the ratio of p-Akt/Akt and p-FoxO1/FoxO1, which could be reversed by SR141716. Moreover, OLGly-induced enhancement of adipogenesis, activation of insulin-mediated Akt signaling pathway and inactivation of FoxO1 were effectively blocked by Wortmannin, a specific PI3K/Akt inhibitor, indicating the essential role of Akt signaling pathway in the process of OLGly-stimulated 3T3-L1 adipogenesis. In conclusion, OLGly, a lipoamino acid, was able to promote 3T3-L1 adipogenesis through the activation of CB1 receptor and the enhancement of insulin-mediated Akt signaling pathway. These findings suggested the potential role of OLGly in increasing insulin sensitivity and suppressing obesity and diabetes. PMID- 26365348 TI - Expression, purification, crystallization and structure determination of the N terminal domain of Fhb, a factor H binding protein from Streptococcus suis. AB - Fhb is a surface virulence protein from Streptococcus suis, which could aid bacterial evasion of host innate immune defense by recruiting complement regulator factor H to inactivate C3b deposited on bacterial surface in blood. Here we successfully expressed and purified the N terminal domain of Fhb (N-Fhb) and obtained crystals of the N-Fhb by sitting-drop vapor diffusion method with a resolution of 1.50 A. The crystals belong to space group C2 with unit cell parameters a = 127.1 A, b = 77.3 A, c = 131.6 A, alpha = 90 degrees , beta = 115.9 degrees , gamma = 90 degrees . The structure of N-Fhb was determined by SAD method and the core structure of N-Fhb is a beta sandwich. We speculated that binding of Fhb to human factor H may be mainly mediated by surface amino acids with negative charges. PMID- 26365349 TI - Evans Blue is not a suitable inhibitor of the epithelial sodium channel delta subunit. AB - The Epithelial Sodium Channel (ENaC) is a heterotrimeric ion channel which can be either formed by assembly of its alpha-, beta- and gamma-subunits or, alternatively, its delta-, beta- and gamma-subunits. The physiological function of alphabetagamma-ENaC is well established, but the function of deltabetagamma ENaC remains elusive. The azo-dye Evans Blue (EvB) has been routinely used to discriminate between the two channel isoforms by decreasing transmembrane currents and amiloride-sensitive current fractions of deltabetagamma-ENaC expressing Xenopus oocytes. Even though these results could be reproduced, it was found by precipitation experiments and spectroscopic methods that the cationic amiloride and the anionic EvB directly interact in solution, forming a strong complex. Thereby a large amount of pharmacologically available amiloride is removed from physiological buffer solutions and the effective amiloride concentration is reduced. This interaction did not occur in the presence of albumin. In microelectrode recordings, EvB was able to abrogate the block of deltabetagamma-ENaC by amiloride or its derivative benzamil. In sum, EvB reduces amiloride-sensitive ion current fractions in electrophysiological experiments. This is not a result of a specific inhibition of deltabetagamma-ENaC but rather represents a pharmacological artefact. EvB should therefore not be used as an inhibitor of delta-ENaC. PMID- 26365350 TI - Follistatin-like 1 attenuates differentiation and survival of erythroid cells through Smad2/3 signaling. AB - Hematopoiesis is a complex process tightly controlled by sets of transcription factors in a context-dependent and stage-specific manner. Smad2/3 transcription factor plays a central role in differentiation and survival of erythroid cells. Here we report that follistatin-like 1 (FSTL1) treatment impairs hemin-induced erythroid differentiation and cell survival. FSTL1 differentially regulates transforming growth factor beta (TGF-beta) and bone morphogenetic protein (BMP) signaling. Blockade of Smad2/3 signaling with the ALK5/type I TGF-betaR kinase inhibitor, SB-525334, was efficacious for rescue of erythroid differentiation blockage and apoptosis. Reversely, activation of Smad1/5/8 signaling with BMP4 cannot rescue FSTL1-mediated erythroid differentiation blockage and apoptosis. Collectively, these data provide mechanistic insight into the regulation of erythropoiesis by FSTL1 signaling and lay a foundation for exploring FSTL1 signaling as a therapeutic target for anemia. PMID- 26365351 TI - ATP selection in a random peptide library consisting of prebiotic amino acids. AB - Based upon many theoretical findings on protein evolution, we proposed a ligand selection model for the origin of proteins, in which the most ancient proteins originated from ATP selection in a pool of random peptides. To test this ligand selection model, we constructed a random peptide library consisting of 15 types of prebiotic amino acids and then used cDNA display to perform six rounds of in vitro selection with ATP. By means of next-generation sequencing, the most prevalent sequence was defined. Biochemical and biophysical characterization of the selected peptide showed that it was stable and foldable and had ATP hydrolysis activity as well. PMID- 26365352 TI - A novel splice variant of the decapentaplegic (dpp) gene in the wild silkworm, Bombyx mandarina. AB - Decapentaplegic (dpp) is a member of the transforming growth factor-beta superfamily. Although the dpp gene and related pathways are known to play important roles in insect development, few studies have examined its function in Bombyx mori and Bombyx mandarina. To date, there have been no previous reports on novel splice variants of dpp in silkworm. In the present study, we conducted RT PCR to examine dpp expression in the mid-gut tissue of B. mandarina and discovered a novel dpp isoform. The isoform sequence was confirmed using sequencing analysis and found to have 333 bp deletion compared to full-length cDNA encoding dpp. The deleted sequence encodes a region of the latency associated peptide (LAP) region of transforming growth factor-beta (TGF-beta), which may affect the activity and specificity of TGF-beta. Using variant calling analyses, we detected 7 candidate single nucleotide variants (SNVs) for different alternative splicing in dpp. This is the first report of a novel splice variant of the dpp gene in B. mandarina and these results provide insight about the domestication process and distinct phenotypic traits of B. mori and B. mandarina. PMID- 26365353 TI - Binding of dihydroxynaphthyl aryl ketones to tubulin colchicine site inhibits microtubule assembly. AB - Dihydroxynaphthyl aryl ketones 1-5 have been evaluated for their abilities to inhibit microtubule assembly and the binding to tubulin. Compounds 3, 4 and 5 displayed competitive inhibition against colchicine binding, and docking analysis showed that they bind to the tubulin colchicine-binding pocket inducing sheets instead of microtubules. Remarkable differences in biological activity observed among the assayed compounds seem to be related to the structure and position of the aryl substituent bonded to the carbonyl group. Compounds 2, 3 and 4, which contain a heterocyclic ring, presented higher affinity for tubulin compared to the carbocyclic analogue 5. Compound 4 showed the best affinity of the series, with an IC50 value of 2.1 MUM for microtubule polymerization inhibition and a tubulin dissociation constant of 1.0 +/- 0.2 MUM, as determined by thermophoresis. Compound 4 was more efficacious in disrupting microtubule assembly in vitro than compound 5 although it contains the trimethoxyphenyl ring present in colchicine. Hydrogen bonds with Asn101 of alpha-tubulin seem to be responsible for the higher affinity of compound 4 respects to the others. PMID- 26365354 TI - De novo characterization of Panax japonicus C. A. Mey transcriptome and genes related to triterpenoid saponin biosynthesis. AB - Panax japonicus C.A.Mey, the traditional medicinal herb in the Araliaceae family, has been used as a tonic, anti-inflammatory and haemostatic agent in China for more than thousand years. Its clinical effects are mainly due to the presence of triterpenoid saponins. However, little is known at the genetic level about how saponins are biosynthesized in this plant. We have therefore performed the de novo transcriptome assembly and high throughput RNA-seq analysis for P. japonicus. 66,403 unigenes were assembled from 19.6 Gbp raw data, and 34,639 unigenes were annotated. After annotation, 29 unigenes involved in putative backbone biosynthesis of triterpenoid saponin were selected. Additionally, 34 Cytochrome P450 and 18 UDP-glycosyltransferase unigenes were predicted based on the annotation, which were related to the saponin backbone modification. The expression level of related key genes were further verified by qPCR analysis. The results of this study provide the most comprehensive expressed sequence resources for P. japonicus, which will enlarge the available P. japonicus gene pool and facilitate further genome-wide research and analyses in this species. PMID- 26365355 TI - Effects of host heterogeneity on pathogen diversity and evolution. AB - Phenotypic variation is common in most pathogens, yet the mechanisms that maintain this diversity are still poorly understood. We asked whether continuous host variation in susceptibility helps maintain phenotypic variation, using experiments conducted with a baculovirus that infects gypsy moth (Lymantria dispar) larvae. We found that an empirically observed tradeoff between mean transmission rate and variation in transmission, which results from host heterogeneity, promotes long-term coexistence of two pathogen types in simulations of a population model. This tradeoff introduces an alternative strategy for the pathogen: a low-transmission, low-variability type can coexist with the high-transmission type favoured by classical non-heterogeneity models. In addition, this tradeoff can help explain the extensive phenotypic variation we observed in field-collected pathogen isolates, in traits affecting virus fitness including transmission and environmental persistence. Similar heterogeneity tradeoffs might be a general mechanism promoting phenotypic variation in any pathogen for which hosts vary continuously in susceptibility. PMID- 26365356 TI - Development and Validation of the McMaster Prescribing Competency Assessment for Medical Trainees (MacPCA). AB - BACKGROUND: Prescribing is an essential skill for all physicians, built on knowledge of clinical pharmacology, therapeutics and toxicology across the life cycle. The decline in organized clinical pharmacology training in medical schools, combined with an expanding pharmacopeia and increasing complexity of patient care, makes prescribing competency difficult for medical students to master. OBJECTIVES: To develop and validate the McMaster Prescribing Competency Assessment (MacPCA), an online tool suitable for evaluating clinical pharmacology knowledge and prescribing skills of medical trainees in Canada. METHODS: The MacPCA was developed using an online examination platform scalable to multiple sites across Canada. Questions represented 8 domains of safe and effective prescribing with level of difficulty aimed at a final year medical student. Validation assessment concentrated on face and construct validity. RESULTS: 58 participants (7, 12 and 21 medical students in Years 1, 2, and 3, respectively and 8 undergraduate controls) were recruited. Mean scores were 31% (SD 13.6), 46% (SD 14.9), 75% (SD 8.3) and 81% (SD 10.5) for the controls, Year 1, Year 2, and Year 3 (final year) students, respectively. Combined Year 2/Year 3 scores were significantly better than control/Year 1 scores (p<0.0001). Final year student feedback indicated the test was fair, clear and unambiguous, aimed at the right level, with sufficient time for completion. CONCLUSIONS: The MacPCA demonstrated good face validity and successfully discriminated between upper year medical students and their junior colleagues. Further expansion of testing and validation is warranted. PMID- 26365357 TI - Perifascial areolar tissue grafting for treating syndactyly with bone fusion in patients with Apert syndrome. AB - Complete syndactyly with bone fusion in patients with Apert syndrome was treated using perifascial areolar tissue (PAT) grafts via a two-stage surgery (i.e. bone separation using inter-bone PAT graft insertion followed by web separation and reconstruction with full-thickness skin grafts). This technique is easy and created nail folds for fingertips. PMID- 26365359 TI - Germinal Matrix-Intraventricular Haemorrhage: still a very important brain lesion in premature infants! PMID- 26365358 TI - Interleukin-13 affects the epithelial sodium channel in the intestine by coordinated modulation of STAT6 and p38 MAPK activity. AB - KEY POINTS: Interleukin-13 (IL-13) causes intestinal epithelial barrier dysfunction, and is implicated in the pathogenesis of Th2-driven intestinal inflammation (e.g. ulcerative colitis). However, it is unclear whether the epithelial sodium channel (ENaC) - the main limiting factor for sodium absorption in the distal colon - is also influenced by IL-13 and if so, by what mechanism(s). We demonstrate in an intestinal cell model as well as in mouse distal colon that IL-13 causes reduced ENaC activity. We show that IL-13 impairs ENaC-dependent sodium transport by activating the JAK1/2-STAT6 signalling pathway. These results improve our understanding of the mechanisms through which IL-13 functions as a key effector cytokine in ulcerative colitis, thereby contributing to the distinct pathology of this disease. ABSTRACT: Interleukin-13 (IL-13) has been strongly implicated in the pathogenesis of ulcerative colitis, possibly by disrupting epithelial integrity. In the distal colon, the epithelial sodium channel (ENaC) is an important factor in the regulation of sodium absorption, and therefore plays a critical role in minimizing intestinal sodium and water losses. In the present study, we investigated whether IL-13 also acts as a potent modulator of epithelial sodium transport via ENaC, and the signalling components involved. The effect of IL-13 on ENaC was examined in HT-29/B6-GR/MR human colon cells, as well as in mouse distal colon, by measuring amiloride sensitive short-circuit current (ISC ) in Ussing chambers. The expression levels of ENaC subunits and the cellular components that contribute to ENaC activity were analysed by qRT-PCR and promoter gene assay. We show that IL-13, in both the cell model and in native intestinal tissue, impaired epithelial sodium absorption via ENaC (JNa ) as a result of decreased transcription levels of beta- and gamma ENaC subunits and SGK1, a post-translational regulator of ENaC activity, due to impaired promoter activity. The reduction in JNa was prevented by inhibition of JAK1/2-STAT6 signalling. This inhibition also affected the IL-13-induced decrease in p38 MAPK phosphorylation. The contribution of STAT6 to IL-13-mediated ENaC inactivation was confirmed in a STAT6(-/-) mouse model. In conclusion, these results indicate that IL-13, the levels of which are elevated in ulcerative colitis, contributes to impaired ENaC activity via modulation of the STAT6/p38 MAPK pathways. PMID- 26365360 TI - Chipping away at duration of therapy for idiopathic acute eosinophilic pneumonia. PMID- 26365361 TI - Phosphonium salt incorporated hypercrosslinked porous polymers for CO2 capture and conversion. AB - Various novel hypercrosslinked porous polymers with phosphonium salt incorporated into their networks were developed. These porous materials have high BET surface areas (up to 1168 m(2) g(-1)) and can be used to selectively capture CO2 and efficiently convert CO2 into cyclic carbonates. PMID- 26365362 TI - Chloroquine: An Old Drug with New Perspective Against Giardiasis. AB - The occurrence of treatment failures to first-line treatment for giardiasis, one of the most widespread although neglected parasitic disease, has long been recognised. Nowadays, it starts to represent a great challenge to clinicians, especially in endemic countries. This requires the introduction of new drug interventions, but the development of novel drugs is a time and money consuming effort with most of the compounds never reaching the market. Consequently, alternative strategies are needed, especially for the treatment of giardiasis. Chloroquine (CQ), a synthetic drug developed as antimalarial agent, has been shown to also exert antigiardial activity. Here, we present a mini-research summarizing results on the treatment of human clinical cases with CQ, going through in vitro research, case report, and case series to human clinical trials, highlighting the benefits and mentioning possible adverse effects. PMID- 26365363 TI - The cardioprotective effect of hypoxic and ischemic preconditioning in dogs with myocardial ischemia-reperfusion injury using a double-bypass model. AB - AIMS: The effects of preconditioning on cardioprotection have mainly been studied in vitro. No sufficient in vivo experiments have been performed to optimize ischemic preconditioning (IPC) or hypoxic preconditioning (HPC) for clinical applications. The purpose of this study was to establish a canine double-bypass model to examine the effect of IPC and HPC on cardiomyocytes and heart function. MATERIALS AND METHODS: A double-bypass procedure to enable independent control of systemic and coronary circulation was established in dogs. The animals were divided into control, HPC, and IPC groups (n=6 each). Indicators of cardiac function, including cardiodynamics, hemodynamics, ATP, and cardiac troponin I (cTnI) levels; myocardium morphology; and myocardiocyte apoptosis were determined. KEY FINDINGS: Both IPC and HPC attenuated the reperfusion-induced decrease in left ventricular end systolic pressure seen in the control group. Both the HPC and IPC groups had lower serum cTnI levels, better myocardiocyte histology, and lower rates of apoptosis compared to the control group without preconditioning. HPC reduced the abnormal cardiomyocyte histology and apoptosis to a greater extent than IPC, and only HPC significantly restored the depletion of ATP. SIGNIFICANCE: This study demonstrates the effectiveness of the double bypass model for the optimized study of both HPC and IPC. The results suggest that HPC may provide better cardioprotection than IPC. PMID- 26365364 TI - [Evidence-based aspects of clinical mastitis treatment]. AB - Mastitis is one of the most common and expensive diseases in dairy cattle. The decision to treat clinical mastitis is usually made without any knowledge of the etiology, and can therefore only be evidence-based to a limited extent. Evidence based medicine relies essentially on a combination of one's own clinical competence and scientific findings. In mastitis therapy, those insights depend mostly on pathogen-specific factors. Therefore, in evidence-based therapeutic decision making the pathogen identification should serve as a basis for the consideration of scientifically validated therapeutic concepts. The present paper considers evidence-based treatment of clinical mastitis based on a literature review. The authors conclude that an anti-inflammatory treatment using an NSAID should be conducted regardless of the pathogen. However, the choice of an antibiotic therapy depends on the mastitis causative pathogen, clinical symptoms and the animal itself. In principle, a local antibiotic treatment should be chosen for mild and moderate mastitis. It should be noted, that the benefit of an antibiotic therapy for coliform infections is questionable. With knowledge concerning the pathogen, it appears entirely reasonable to refrain from an antibiotic therapy. For severe (i. e. feverish) mastitis, a parenteral antibiotic therapy should be selected. An extension of the antibiotic therapy beyond the manufacturer's information is only reasonable for streptococcal infections. It is important to make the decision on a prolonged antibiotic therapy only with the knowledge of the mastitis-causative pathogen. In terms of the therapy of a staphylococcus or streptococcus infection, a narrow-spectrum antibiotic from the penicillin family should be adopted when selecting the active agents. PMID- 26365365 TI - Further improved stability criteria for uncertain T-S fuzzy systems with time varying delay by (m,N)-delay-partitioning approach. AB - This paper mainly focuses on the robust stability criteria for uncertain T-S fuzzy systems with time-varying delay by (m,N)-delay-partitioning approach. A modified augmented LKF is established by partitioning the delay in all integral terms. Via taking into account of (i) the relationship between each subinterval and time-varying delay and (ii) the independent upper bounds of the delay derivative in the various delay intervals, some new results on tighter bounding inequalities such as Peng-Park's integral inequality and Free-Matrix-based integral inequality are introduced to effectively reduce the enlargement in bounding the derivative of LKF as much as possible, therefore, significant less conservative results can be expected in terms of es and LMIs, which can be solved efficiently with the Matlab LMI toolbox. Furthermore, it is worth mentioning that, when the delay-partitioning number m is fixed, the conservatism is gradually reduced with the increase of another delay-partitioning number N, but without increasing any computing burden. Finally, two numerical examples are included to show that the proposed method is less conservative than existing ones. PMID- 26365366 TI - Distributed-observer-based cooperative control for synchronization of linear discrete-time multi-agent systems. AB - This paper considers output synchronization of discrete-time multi-agent systems with directed communication topologies. The directed communication graph contains a spanning tree and the exosystem as its root. Distributed observer-based consensus protocols are proposed, based on the relative outputs of neighboring agents. A multi-step algorithm is presented to construct the observer-based protocols. In light of the discrete-time algebraic Riccati equation and internal model principle, synchronization problem is completed. At last, numerical simulation is provided to verify the effectiveness of the theoretical results. PMID- 26365367 TI - Minimally invasive right colectomy: challenges and clinical practice. AB - AIM: Since the introduction of laparoscopic and robotic technology in surgical practice, there have been multiple reports and a few clinical trials on their use in colorectal surgery. Although the application of laparoscopy to right colectomy has been increasingly adopted in many institutions around the world, there are still several open issues regarding the effective role of robotics and single incision surgery. This is a review of the relevant surgical literature evaluating the risks, benefits, and costs of minimally invasive approaches to right colectomy (RC) surgery. METHODS: Retrospective and prospective articles spanning the past 20 years were reviewed to identify the current application of minimally invasive surgery in RC. A review of the most relevant papers comparing open vs. laparoscopic vs. robotic approaches will illustrate the role of minimally invasive surgery in current clinical practice in terms of surgical outcomes, technical advantages and oncological outcomes. We then pooled the evidence for and against the application of laparoscopy and robotics in intracorporeal vs. extracorporeal anastomosis creation, single incision and natural orifice surgery. RESULTS: Evidence shows that compared to open surgery, laparoscopic RC provides lower postoperative morbidity, faster return to normal bowel function and a shorter length of hospital stay, with a similar oncological outcome. The application of robotics to RC procedure has proven to be safe and feasible, however the intraoperative and postoperative outcomes are similar with the laparoscopic technique and no clear advantages have been demonstrated. When adopted in a single incision technique and natural orifice surgery, robotics can help to overcome the limitations of laparoscopy, enabling the surgeon to perform scar-less surgery. CONCLUSION: Laparoscopy surgery, whenever performed by adequately trained surgeons, can be safely applied to right colectomy and should be considered as the gold standard procedure. In terms of robotic surgery, to date, this technology needs more evidence from multicenter randomized clinical trials. New tools and instruments are needed to expand the field of single incision and natural orifice surgery, and make it available in current clinical practice. PMID- 26365368 TI - BMI, body fat mass and plasma leptin level in relation to cardiovascular diseases risk factors among adolescents in Taitung. AB - BACKGROUND: To investigate the risk factors associated with cardiovascular diseases and its relation to BMI, body fat mass and plasma leptin level among adolescents in Taitung, Taiwan. METHODS: A cross-sectional Taitung Children Heart Study for 500 young adolescents between ages 13 and 15 was conducted. Gender specific regression models were used to determine the associations between BMI, percentage of body fat mass, plasma leptin level and seven CVDs risk factors (systolic and diastolic blood pressure, mean arterial pressure, triglycerides, total cholesterol, HDL-cholesterol and LDL-cholesterol) before and after adjusting for weight status and age. RESULTS: After adjusting for weight status and age, BMI was positively associated with systolic BP, triglycerides, LDL cholesterol levels but negatively associated with HDL-cholesterol level in boys while positively associated with systolic and diastolic BP, mean arterial pressure, and LDL-cholesterol level in girls. The percentage of body fat mass was positively associated with triglycerides, total cholesterol, and LDL-cholesterol in boys while positively associated with systolic BP, total cholesterol, and LDL cholesterol in girls. Plasma leptin was positively associated with triglycerides, total cholesterol and LDL-cholesterol in boys but no statistically significant associations with CVDs risk factors in girls. A strong relationship between the percentage of body fat mass and plasma leptin appeared among all participants (r=0.59, p<0.01). CONCLUSIONS: BMI, body fat mass and plasma leptin level may be used to identify certain CVDs risk factors among Taitung adolescents. Future researches could consider measuring body fat mass in the relationship of CVDs risk factors instead of plasma leptin among young adolescents. PMID- 26365369 TI - [Agroindustrial wastes methanization and bacterial composition in anaerobic digestion]. AB - The tons of organic waste that are annually generated by agro-industry, can be used as raw material for methane production. For this reason, it is important to previously perform biodegradability tests to organic wastes for their full scale methanization. This paper addresses biodegradability, methane production and the behavior of populations of eubacteria and archaeabacteria during anaerobic digestion of banana, mango and papaya agroindustrial wastes. Mango and banana wastes had higher organic matter content than papaya in terms of their volatile solids and total solid rate (94 and 75% respectively). After 63 days of treatment, the highest methane production was observed in banana waste anaerobic digestion: 63.89ml CH4/per gram of chemical oxygen demand of the waste. In the PCR-DGGE molecular analysis, different genomic footprints with oligonucleotides for eubacteria and archeobacteria were found. Biochemical methane potential results proved that banana wastes have the best potential to be used as raw material for methane production. The result of a PCR- DGGE analysis using specific oligonucleotides enabled to identify the behavior of populations of eubacteria and archaeabacteria present during the anaerobic digestion of agroindustrial wastes throughout the process. PMID- 26365371 TI - Anticholinergic risk: Use and limitations of anticholinergic scales. PMID- 26365370 TI - Walking patterns and hip contact forces in patients with hip dysplasia. AB - INTRODUCTION: Several studies have investigated walking characteristics in hip dysplasia patients, but so far none have described all hip rotational degrees of freedom during the whole gait cycle. This descriptive study reports 3D joint angles and torques, and furthermore extends previous studies with muscle and joint contact forces in 32 hip dysplasia patients and 32 matching controls. METHODS: 3D motion capture data from walking and standing trials were analysed. Hip, knee, ankle and pelvis angles were calculated with inverse kinematics for both standing and walking trials. Hip, knee and ankle torques were calculated with inverse dynamics, while hip muscle and joint contact forces were calculated with static optimisation for the walking trials. RESULTS: No differences were found between the two groups while standing. While walking, patients showed decreased hip extension, increased ankle pronation and increased hip abduction and external rotation torques. Furthermore, hip muscle forces were generally lower and shifted to more posteriorly situated muscles, while the hip joint contact force was lower and directed more superiorly. CONCLUSION: During walking, patients showed lower and more superiorly directed hip joint contact force, which might alleviate pain from an antero-superiorly degenerated joint. PMID- 26365372 TI - Thromboembolic events in patients with severe pandemic influenza A/H1N1. AB - BACKGROUND: The 2009 pandemic influenza A/H1N1 developed as a novel swine influenza which caused more diseases among younger age groups than in the elderly. Severe hypoxemic respiratory failure from A/H1N1 pneumonia resulted in an increased need for ICU beds. Several risk groups were identified that were at a higher risk for adverse outcomes. Pregnant women were a particularly vulnerable group of patients The CDC reported on the first ten patients with severe illness and acute hypoxemic respiratory failure associated with A/H1N1 infection, none of whom were pregnant, but they noticed that half of the patients had a pulmonary embolism. METHODS: During a four-month period from September to December 2009, 252 patients were admitted to our hospital with confirmed pandemic influenza H1N1 by real-time reverse transcriptase-polymerase chain reaction test (rRT-PCR). We cared for twenty patients (7.9%) admitted to MICU with severe A/H1N1. Results on Thrombotic events were identified in five (25%) of our critically ill patients. CONCLUSIONS: We recommend that patients with severe influenza A/H1N1 pneumonitis and respiratory failure be administered DVT prophylaxis in particular if there are additional risk factors for TVE. Further prospective studies on the relationship of influenza A/H1N1 and VTE are needed. PMID- 26365373 TI - Acute Complex Care Model: An organizational approach for the medical care of hospitalized acute complex patients. AB - BACKGROUND: Chronic diseases are the major cause of death (59%) and disability worldwide, representing 46% of global disease burden. According to the Future Hospital Commission of the Royal College of Physicians, Medical Division (MD) will be responsible for all hospital medical services, from emergency to specialist wards. The Hospital Acute Care Hub will bring together the clinical areas of the MD that focus on the management of acute medical patients. The Chronic Care Model (CCM) places the patient at the center of the care system enhancing the community's social and health support, pathways and structures to keep chronic, frail, poly-pathological people at home or out of the hospital. The management of such patients in the hospital still needs to be solved. Hereby, we propose an innovative model for the management of the hospital's acute complex patients, which is the hospital counterpart of the CCM. ACUTE COMPLEX CARE MODEL (ACCM): The target population are acutely ill complex and poly-pathological patients (AICPPs), admitted to hospital and requiring high technology resources. The mission is to improve the management of medical admissions through pre defined intra-hospital tracks and a global, multidisciplinary, patient-centered approach. The ACCM leader is an internal medicine specialist (IMS) who summarizes health problems, establishes priorities, and restores health balance in AICPPs. CONCLUSIONS: The epidemiological transition leading to a progressive increase in "chronically unstable" and complex patients needing frequent hospital treatment, inevitably enhances the role of hospital IMS in the coordination and delivery of care. ACCM represents a practical response to this epochal change of roles. PMID- 26365374 TI - Physical activity in pregnant women with Class III obesity: A qualitative exploration of attitudes and behaviours. AB - OBJECTIVE: To explore the barriers and facilitators to physical activity and lifestyle interventions in pregnant women with Class III obesity (body mass index >40 kg/m(2)). DESIGN: Qualitative study using in-depth, semi-structure interviews framed by the Theory of Planned Behaviour. Semi-structured, in-depth interviews were conducted using a topic guide. Data analysis was undertaken using a Framework Approach and was informed by the theory of planned behaviour. Recruitment and analysis continued until data saturation was reached. SETTING: Participants were recruited from an antenatal clinic for women with Class III obesity. PARTICIPANTS: Pregnant women (n=13) with Class III obesity. MEASUREMENTS AND OUTCOMES: Three major themes emerged from the data analysis: having a healthy lifestyle awareness, complex barriers to lifestyle changes and having personalised solutions to promote healthy lifestyle. Women were aware of the benefits of physical activity during pregnancy but had complex barriers to engaging with activity. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: future lifestyle interventions for women with Class III in pregnancy should take into account individual, societal and support barriers towards weight management and lifestyle choices in pregnancy. Programs that provide personalised support which are sensitive to the specific physical and psychological needs of women with Class III obesity which focus on the benefits and safety of physical activity for both mother and baby may be more likely to be successful. Further research is needed to explore the feasibility and acceptability of tailored programs. PMID- 26365375 TI - Consistent Comparisons of Attainment and Shortfall Inequality: A Critical Examination. AB - An inequality measure is 'consistent' if it ranks distributions the same irrespective of whether health quantities are represented in terms of attainments or shortfalls. This consistency property severely restricts the set of admissible inequality measures. We show that, within a more general setting of separate measures for attainments and shortfalls, the consistency property is a combination of two conditions. The first is a compelling rationality condition that says that the attainment measure should rank attainment distributions as the shortfall measure ranks shortfall distributions. The second is an overly demanding condition that says that the attainment measure and the shortfall measure should be identical. By dropping the latter condition, the restrictions on the admissible inequality measures disappear. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26365376 TI - Early metabolic responses to lithium/pilocarpine-induced status epilepticus in rat brain. AB - The lithium-pilocarpine model of status epilepticus is a well-known animal model of temporal lobe epilepsy. We combined this model with in vivo microdialysis to investigate energy metabolites and acute cellular membrane damage during seizure development. Rats were implanted with dialysis probes and pretreated with lithium chloride (127 mg/kg i.p.). Twenty-four hours later, they received pilocarpine (30 mg/kg s.c.) which initiated seizures within 30 min. In the dialysate from rat hippocampus, we observed a transient increase in glucose and a prominent, five fold increase in lactate during seizures. Lactate release was because of neuronal activation as it was strongly reduced by infusion of tetrodotoxin, administration of atropine or when seizures were terminated by diazepam or ketamine. In ex vivo assays, mitochondrial function as measured by respirometry was not affected by 90 min of seizures. Extracellular levels of choline, however, increased two-fold and glycerol levels 10-fold, which indicate cellular phospholipid breakdown during seizures. Within 60 min of pilocarpine administration, hydroxylation of salicylate increased two-fold and formation of isoprostanes 20-fold, revealing significant oxidative stress in hippocampal tissue. Increases in lactate, glycerol and isoprostanes were abrogated, and increases in choline were completely prevented, when hippocampal probes were perfused with calcium-free solution. Similarly, administration of pregabalin (100 mg/kg i.p.), a calcium channel ligand, 15 min prior to pilocarpine strongly attenuated parameters of membrane damage and oxidative stress. We conclude that seizure development in a rat model of status epilepticus is accompanied by increases in extracellular lactate, choline and glycerol, and by oxidative stress, while mitochondrial function remains intact for at least 90 min. Membrane damage depends on calcium influx and can be prevented by treatment with pregabalin. Status epilepticus (SE) was induced in rats by lithium-pilocarpine ('Pilo') administration, and extracellular metabolites were measured by microdialysis. Seizures caused several fold increases in lactate levels which were attenuated by diazepam ('Diaz'), ketamine, atropine and tetrodotoxin (TTX). Indicators of oxidative stress and membrane damage were also increased during seizures. Omission of calcium and pregabalin, a calcium channel blocker, reduced cellular damage induced by SE. PMID- 26365378 TI - ESCRTs Cooperate with a Selective Autophagy Receptor to Mediate Vacuolar Targeting of Soluble Cargos. AB - Autophagy transports cytosolic materials into lysosomes/vacuoles either in bulk or selectively. Selective autophagy requires cargo receptor proteins, which usually link cargos to the macroautophagy machinery composed of core autophagy related (Atg) proteins. Here, we show that fission yeast Nbr1, a homolog of mammalian autophagy receptor NBR1, interacts with and facilitates the transport of two cytosolic hydrolases into vacuoles, in a way reminiscent of the budding yeast cytoplasm-to-vacuole targeting (Cvt) pathway, a prototype of selective autophagy. We term this pathway Nbr1-mediated vacuolar targeting (NVT). Surprisingly, unlike the Cvt pathway, the NVT pathway does not require core Atg proteins. Instead, it depends on the endosomal sorting complexes required for transport (ESCRTs). NVT components colocalize with ESCRTs at multivesicular bodies (MVBs) and rely on ubiquitination for their transport. Our findings demonstrate the ability of ESCRTs to mediate highly selective autophagy of soluble cargos, and suggest an unexpected mechanistic versatility of autophagy receptors. PMID- 26365377 TI - Distinct but Concerted Roles of ATR, DNA-PK, and Chk1 in Countering Replication Stress during S Phase. AB - The ATR-Chk1 pathway is critical for DNA damage responses and cell-cycle progression. Chk1 inhibition is more deleterious to cycling cells than ATR inhibition, raising questions about ATR and Chk1 functions in the absence of extrinsic replication stress. Here we show that a key role of ATR in S phase is to coordinate RRM2 accumulation and origin firing. ATR inhibitor (ATRi) induces massive ssDNA accumulation and replication catastrophe in a fraction of early S phase cells. In other S-phase cells, however, ATRi induces moderate ssDNA and triggers a DNA-PK and Chk1-mediated backup pathway to suppress origin firing. The backup pathway creates a threshold such that ATRi selectively kills cells under high replication stress, whereas Chk1 inhibitor induces cell death at a lower threshold. The levels of ATRi-induced ssDNA correlate with ATRi sensitivity in a panel of cell lines, suggesting that ATRi-induced ssDNA could be predictive of ATRi sensitivity in cancer cells. PMID- 26365379 TI - The Replication Checkpoint Prevents Two Types of Fork Collapse without Regulating Replisome Stability. AB - The ATR replication checkpoint ensures that stalled forks remain stable when replisome movement is impeded. Using an improved iPOND protocol combined with SILAC mass spectrometry, we characterized human replisome dynamics in response to fork stalling. Our data provide a quantitative picture of the replisome and replication stress response proteomes in 32 experimental conditions. Importantly, rather than stabilize the replisome, the checkpoint prevents two distinct types of fork collapse. Unsupervised hierarchical clustering of protein abundance on nascent DNA is sufficient to identify protein complexes and place newly identified replisome-associated proteins into functional pathways. As an example, we demonstrate that ZNF644 complexes with the G9a/GLP methyltransferase at replication forks and is needed to prevent replication-associated DNA damage. Our data reveal how the replication checkpoint preserves genome integrity, provide insights into the mechanism of action of ATR inhibitors, and will be a useful resource for replication, DNA repair, and chromatin investigators. PMID- 26365381 TI - The PINK1-PARKIN Mitochondrial Ubiquitylation Pathway Drives a Program of OPTN/NDP52 Recruitment and TBK1 Activation to Promote Mitophagy. AB - Damaged mitochondria are detrimental to cellular homeostasis. One mechanism for removal of damaged mitochondria involves the PINK1-PARKIN pathway, which poly ubiquitylates damaged mitochondria to promote mitophagy. We report that assembly of ubiquitin chains on mitochondria triggers autophagy adaptor recruitment concomitantly with activation of the TBK1 kinase, which physically associates with OPTN, NDP52, and SQSTM1. TBK1 activation in HeLa cells requires OPTN and NDP52 and OPTN ubiquitin chain binding. In addition to the known role of S177 phosphorylation in OPTN on ATG8 recruitment, TBK1-dependent phosphorylation on S473 and S513 promotes ubiquitin chain binding in vitro as well as TBK1 activation, OPTN mitochondrial retention, and efficient mitophagy in vivo. These data reveal a self-reinforcing positive feedback mechanism that coordinates TBK1 dependent autophagy adaptor phosphorylation with the assembly of ubiquitin chains on mitochondria to facilitate efficient mitophagy, and mechanistically links genes mutated in Parkinson's disease and amyotrophic lateral sclerosis in a common selective autophagy pathway. PMID- 26365380 TI - P16INK4a Upregulation Mediated by SIX6 Defines Retinal Ganglion Cell Pathogenesis in Glaucoma. AB - Glaucoma, a blinding neurodegenerative disease, whose risk factors include elevated intraocular pressure (IOP), age, and genetics, is characterized by accelerated and progressive retinal ganglion cell (RGC) death. Despite decades of research, the mechanism of RGC death in glaucoma is still unknown. Here, we demonstrate that the genetic effect of the SIX6 risk variant (rs33912345, His141Asn) is enhanced by another major POAG risk gene, p16INK4a (cyclin dependent kinase inhibitor 2A, isoform INK4a). We further show that the upregulation of homozygous SIX6 risk alleles (CC) leads to an increase in p16INK4a expression, with subsequent cellular senescence, as evidenced in a mouse model of elevated IOP and in human POAG eyes. Our data indicate that SIX6 and/or IOP promotes POAG by directly increasing p16INK4a expression, leading to RGC senescence in adult human retinas. Our study provides important insights linking genetic susceptibility to the underlying mechanism of RGC death and provides a unified theory of glaucoma pathogenesis. PMID- 26365382 TI - USP7 Acts as a Molecular Rheostat to Promote WASH-Dependent Endosomal Protein Recycling and Is Mutated in a Human Neurodevelopmental Disorder. AB - Endosomal protein recycling is a fundamental cellular process important for cellular homeostasis, signaling, and fate determination that is implicated in several diseases. WASH is an actin-nucleating protein essential for this process, and its activity is controlled through K63-linked ubiquitination by the MAGE-L2 TRIM27 ubiquitin ligase. Here, we show that the USP7 deubiquitinating enzyme is an integral component of the MAGE-L2-TRIM27 ligase and is essential for WASH mediated endosomal actin assembly and protein recycling. Mechanistically, USP7 acts as a molecular rheostat to precisely fine-tune endosomal F-actin levels by counteracting TRIM27 auto-ubiquitination/degradation and preventing overactivation of WASH through directly deubiquitinating it. Importantly, we identify de novo heterozygous loss-of-function mutations of USP7 in individuals with a neurodevelopmental disorder, featuring intellectual disability and autism spectrum disorder. These results provide unanticipated insights into endosomal trafficking, illuminate the cooperativity between an ubiquitin ligase and a deubiquitinating enzyme, and establish a role for USP7 in human neurodevelopmental disease. PMID- 26365383 TI - Automated image-based analysis of spatio-temporal fungal dynamics. AB - Due to their ability to grow in complex environments, fungi play an important role in most ecosystems and have for that reason been the subject of numerous studies. Some of the main obstacles to the study of fungal growth are the heterogeneity of growth environments and the limited scope of laboratory experiments. Given the increasing availability of image capturing techniques, a new approach lies in image analysis. Most previous image analysis studies involve manual labelling of the fungal network, tracking of individual hyphae, or invasive techniques that do not allow for tracking the evolution of the entire fungal network. In response, this work presents a highly versatile tool combining image analysis and graph theory to monitor fungal growth through time and space for different fungal species and image resolutions. In addition, a new experimental set-up is presented that allows for a functional description of fungal growth dynamics and a quantitative mutual comparison of different growth behaviors. The presented method is completely automated and facilitates the extraction of the most studied fungal growth features such as the total length of the mycelium, the area of the mycelium and the fractal dimension. The compactness of the fungal network can also be monitored over time by computing measures such as the number of tips, the node degree and the number of nodes. Finally, the average growth angle and the internodal length can be extracted to study the morphology of the fungi. In summary, the introduced method offers an updated and broader alternative to classical and narrowly focused approaches, thus opening new avenues of investigation in the field of mycology. PMID- 26365384 TI - Genome editing in Ustilago maydis using the CRISPR-Cas system. AB - This communication describes the establishment of the type II bacterial CRISPR Cas9 system to efficiently disrupt target genes in the fungal maize pathogen Ustilago maydis. A single step transformation of a self-replicating plasmid constitutively expressing the U. maydis codon-optimized cas9 gene and a suitable sgRNA under control of the U. maydis U6 snRNA promoter was sufficient to induce genome editing. On average 70% of the progeny of a single transformant were disrupted within the respective b gene. Without selection the self-replicating plasmid was lost rapidly allowing transient expression of the CRISPR-Cas9 system to minimize potential long-term negative effects of Cas9. This technology will be an important advance for the simultaneous disruption of functionally redundant genes and gene families to investigate their contribution to virulence of U. maydis. PMID- 26365385 TI - Systematic gene deletion and functional characterization of histidine kinase phosphorelay receptors (HKRs) in the human pathogenic fungus Aspergillus fumigatus. AB - Histidine kinase receptors (HKRs) appear to be a common strategy for model and pathogenic fungi to sense and respond to environmental stresses. In the human pathogen Aspergillus fumigatus, which is responsible for invasive aspergillosis, 13 genes potentially encoding HKRs have been identified. Until now, only three HKRs have been functionally characterized. The aim of this study was to perform the systematic invalidation of A. fumigatus HKR genes and the careful phenotypic characterization of the relevant mutants. This study notably allowed to gain new important insights into the role of HKRs in physiology of A. fumigatus. Actually, we showed that (i) NikA/TcsC could be involved in the cell wall integrity pathway, (ii) Fhk6 and PhkA were involved in the regulation of the "fluffy" developmental program, (iii) PhkB could participate in the regulation of conidiation and (iv) PhkA was implied in the resistance of oxidative stresses. PMID- 26365386 TI - A novel mutation in the POLE2 gene causing combined immunodeficiency. PMID- 26365388 TI - Highly increased levels of IgE antibodies to vaccine components in children with influenza vaccine-associated anaphylaxis. AB - BACKGROUND: Influenza vaccines produced in embryonated eggs might pose a risk to patients with egg allergy. However, patients experiencing influenza vaccine associated anaphylaxis (IVA) do not always have egg allergy. In the 2011-2012 season, an unusually high incidence of IVA was reported in Japan. OBJECTIVE: We sought to identify the cause of the increase in anaphylactic events in 2011-2012 in Japan. METHODS: We collected blood specimens from patients with IVA from all areas of Japan. We analyzed 19 patients with confirmed IVA and 25 age-matched control subjects, including 10 with egg allergy who had no adverse events after corresponding vaccination. ELISA was used to measure specific IgE levels to the trivalent vaccines of several manufacturers and hemagglutinin proteins derived from both egg and cell cultures. Antigen-induced basophil activation was evaluated by measuring CD203c expression by means of flow cytometry. Vaccine excipients were also examined for effects on CD203c expression. RESULTS: None of the patients with IVA had severe egg allergy. Levels of specific IgE antibodies to influenza vaccine antigens, whole-vaccine products from different manufacturers, and hemagglutinin proteins (A H1, H3, and B) derived from both egg and cell cultures were significantly increased in patients with IVA compared with those in control subjects. Influenza vaccine-induced CD203c expression in basophils was also highly enhanced in patients with IVA but not in control subjects. Because IVA was most frequent in patients who received 2-phenoxyethanol (2-PE)-containing vaccine, the effect of this preservative on basophil activation was examined, and the activation was slightly enhanced by 2-PE but not thimerosal. CONCLUSIONS: The 2011-2012 IVA spike in Japan was caused by specific IgE antibodies to influenza vaccine components. Excipients could not be implicated, except for a modest effect of 2-PE. PMID- 26365387 TI - Protein microarrays identify disease-specific anti-cytokine autoantibody profiles in the landscape of immunodeficiency. AB - BACKGROUND: Anti-cytokine autoantibodies (ACAAs) are pathogenic in a handful of rare immunodeficiencies. However, the prevalence and significance of other ACAAs across immunodeficiencies have not yet been described. OBJECTIVE: We profiled ACAAs in a diverse cohort of serum samples from patients with immunodeficiency and assessed the sensitivity and specificity of protein microarrays for ACAA identification and discovery. METHODS: Highly multiplexed protein microarrays were designed and fabricated. Blinded serum samples from a cohort of 58 immunodeficiency patients and healthy control subjects were used to probe microarrays. Unsupervised hierarchical clustering was used to identify clusters of reactivity, and after unblinding, significance analysis of microarrays was used to identify disease-specific autoantibodies. A bead-based assay was used to validate protein microarray results. Blocking activity of serum containing ACAAs was measured in vitro. RESULTS: Protein microarrays were highly sensitive and specific for the detection of ACAAs in patients with autoimmune polyendocrine syndrome type I and pulmonary alveolar proteinosis, detecting ACAA levels consistent with those reported in the published literature. Protein microarray results were validated by using an independent bead-based assay. To confirm the functional significance of these ACAAs, we tested and confirmed the blocking activity of select ACAAs in vitro. CONCLUSION: Protein microarrays are a powerful tool for ACAA detection and discovery, and they hold promise as a diagnostic for the evaluation and monitoring of clinical immunodeficiency. PMID- 26365389 TI - Systematic review with meta-analysis: Lactobacillus rhamnosus GG in the prevention of antibiotic-associated diarrhoea in children and adults. AB - BACKGROUND: The effects of probiotics are strain specific. The clinical effects of each strain need to be evaluated separately. AIM: To evaluate the efficacy of Lactobacillus rhamnosus GG (LGG) in the prevention of antibiotic-associated diarrhoea (AAD) in children and adults. METHODS: The Cochrane Library, MEDLINE, and EMBASE databases were searched up to July 2015, with no language restrictions, for randomised controlled trials (RCTs). Reference lists of reviews and included studies were examined. The quality of evidence (QoE) was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines. RESULTS: Twelve RCTs (1499 participants) were included. Treatment with LGG compared with placebo or no additional treatment reduced the risk of AAD in patients treated with antibiotics from 22.4% to 12.3% (11 RCTs, n = 1308, relative risk, RR: 0.49, 95% confidence interval, CI: 0.29-0.83, low QoE). However, when children and adults were evaluated separately, the difference was significant in children only (five RCTs, n = 445, RR 0.48, 95% CI 0.26-0.89; moderate QoE). In adults, the difference was not significant (six RCTs, n = 863, RR 0.48, 95% CI 0.20-1.15; low QoE), except for in a subset of patients receiving antibiotics as part of Helicobacter pylori eradication therapy (four RCTs, n = 280, RR 0.26, 95% CI 0.11-0.59; low QoE). CONCLUSIONS: This meta-analysis shows that Lactobacillus rhamnosus GG is effective in preventing antibiotic-associated diarrhoea in children and adults treated with antibiotics for any reason. However, the quality of evidence is moderate to low. PMID- 26365390 TI - Evaluation of bronchoscopic lung volume reduction coil treatment results in patients with severe emphysema. AB - INTRODUCTION: Bronchoscopic lung volume reduction coil (BLVR-C) implantation is an alternative therapeutic approach that can be applied together with medical treatment for patients with severe emphysema. BLVR-C is both easier and safer in terms of complications than volume reduction surgery. This study aimed to evaluate medium-term outcomes following BLVR-C treatment. METHODS: Forty patients who underwent BLVR-C between September 2013 and March 2014 were reviewed retrospectively. We compared changes between the baseline and 6-month post procedural results with respect to pulmonary function tests, a 6-min walk test (6MWT), chronic obstructive pulmonary disease (COPD) assessment test (CAT), St. George's Respiratory Questionnaire (SGRQ), and pulmonary artery pressure (PAP) and arterial blood gas analyses. Secondary outcomes included procedure-related and follow-up complications. RESULTS: An average of 9.5 (range: 5-11) coils were placed per lung in an average procedural duration of 20.8 +/- 7.0 min (range: 9 45) min. Six months after BLVR-C treatment, significant improvements were observed in patients' pulmonary function tests and quality of life. Changes were observed in the forced exhalation volume in 1 s (+150 mL), residual volume ( 14.5%), 6MWT (+48 m), SGRQ (-10.5) and CAT Score (-7.5). Changes in the PAP and partial pressure of carbon dioxide values were not significant, and pneumothorax did not occur. In a 6-month follow-up, 11 cases of COPD exacerbation (41.4%), 7 cases of pneumonia (16.9%) and 1 death (2%) occurred. Treatment in 1 case was postponed because of hypotension and bradycardia during the process. CONCLUSION: BLVR-C treatment appears to be effective over the medium-term and safe for patients with severe emphysema. PMID- 26365391 TI - The Application of Bileaflet Mechanical Heart Valves in the Polish Ventricular Assist Device: Physical and Numerical Study and First Clinical Usage. AB - The Polish ventricular assist device (Polvad) has been used successfully in clinical contexts for many years. The device contains two single-disc valves, one at the inlet and one at the outlet connector of the pneumatic pump. Unfortunately, in recent years, a problem has occurred with the availability of single-disc valves. This article presents the possibility of using bileaflet mechanical heart valve prostheses in the Polvad to avoid a discontinuity in clinical use. The study is based on experimental and numerical simulations and comparison of the distribution of flow, pressure, and stress (wall, shear, and turbulent) inside the Polvad chamber and the inlet/outlet connectors fitted with Sorin Monodisc and Sorin Bicarbon Fitline valves. The type and orientation of the inlet valve affects valve performance and flow distribution inside the chamber. Near-wall flow is observed for single-disc valves. In the case of bileaflet valves, the main jet is directed more centrally, with lower shear stress but higher turbulent stress in comparison with single-disc valves. For clinical usage, a 45 degrees orientation of the bileaflet inlet valve was chosen, as this achieves good washing of the inlet area near the membrane paste surface. The Polvad with bileaflet valves has now been used successfully in our clinic for over a year and will continue to be used until new assist devices for heart support are developed. PMID- 26365392 TI - Host-guest supramolecular chemistry in solid-state nanopores: potassium-driven modulation of ionic transport in nanofluidic diodes. AB - We describe the use of asymmetric nanopores decorated with crown ethers for constructing robust signal-responsive chemical devices. The modification of single conical nanopores with 18-crown-6 units led to a nanodevice whose electronic readout, derived from the transmembrane ion current, can be finely tuned over a wide range of K(+) concentrations. The electrostatic characteristics of the nanopore environment arising from host-guest ion-recognition processes taking place on the pore walls are responsible for tuning the transmembrane ionic transport and the rectification properties of the pore. This work illustrates the potential and versatility of host-guest chemistry, in combination with nanofluidic elements, as a key enabler to achieve addressable chemical nanodevices mimicking the ion transport properties and gating functions of specific biological channels. PMID- 26365393 TI - Determination of obesity associated gene variants related to TMEM18 through ultra deep targeted re-sequencing in a case-control cohort for pediatric obesity. AB - Genome-wide association studies (GWAS) have revealed association of a locus approximately 25b downstream of the TMEM18 gene with body mass and obesity. We utilized targeted re-sequencing of the body mass associated locus in proximity of TMEM18 in a case-control population of severely obese children and adolescents from the Stockholm area. We expanded our study to include the TMEM18 gene itself, with the aim of identifying body mass associated genetic variants. Sequencing was performed on the SOLiD platform, on long-range PCR fragments generated through targeted amplification of the regions of interest. Candidate single nucleotide polymorphisms (SNPs) were validated by TaqMan genotyping. We were able to observe 131 SNPs across the re-sequenced regions. Chi squared tests comparing the allele frequencies between cases and controls revealed 57 SNPs as candidates for association with obesity. Validation and replication genotyping revealed robust associations for SNPs within the haplotype block region located downstream from the TMEM18 gene. This study provides a high resolution map of the genetic variation pattern in the TMEM18 gene, as well as the associated haplotype block, and further strengthens the association of variants within the proximal haplotype block with obesity and body mass. PMID- 26365394 TI - The role of mRNA and protein stability in the function of coupled positive and negative feedback systems in eukaryotic cells. AB - Oscillators and switches are important elements of regulation in biological systems. These are composed of coupling negative feedback loops, which cause oscillations when delayed, and positive feedback loops, which lead to memory formation. Here, we examine the behavior of a coupled feedback system, the Negative Autoregulated Frustrated bistability motif (NAF). This motif is a combination of two previously explored motifs, the frustrated bistability motif (FBM) and the negative auto regulation motif (NAR), which both can produce oscillations. The NAF motif was previously suggested to govern long term memory formation in animals, and was used as a synthetic oscillator in bacteria. We build a mathematical model to analyze the dynamics of the NAF motif. We show analytically that the NAF motif requires an asymmetry in the strengths of activation and repression links in order to produce oscillations. We show that the effect of time delays in eukaryotic cells, originating from mRNA export and protein import, are negligible in this system. Based on the reported protein and mRNA half-lives in eukaryotic cells, we find that even though the NAF motif possesses the ability for oscillations, it mostly promotes constant protein expression at the biologically relevant parameter regimes. PMID- 26365395 TI - High-resolution melt curve analysis to confirm the presence of co-circulating isolates of avian nephritis virus in commercial chicken flocks. AB - Avian Nephritis Virus (ANV) has been implicated in poor growth and renal disease of young chickens. This paper describes the development of a reverse transcriptase polymerase chain reaction for the detection of ANV in commercial meat chickens and the use of high-resolution melt curves to detect the presence of genetically different ANVs. Pooled cloacal swabs from both healthy and ill commercial chicken broiler flocks were tested for the presence of ANV using a combination of polymerase chain reaction, molecular cloning, high-resolution melt curve analysis and sequencing. Except for one, all specimens were found to contain two genetically different ANVs. Phylogenetic analysis of the capsid amino acid sequences revealed the presence of four of six groups of ANV identified previously in other countries as well as in two novel groups of ANV. Phylogenetic analysis of nucleotide sequences of partial polymerase, capsid and 3' untranslated regions reveal that the genes of individual ANV virus isolates have different ancestors. This was shown to be due to a template-switching event in the capsid gene that resulted in the 3' end of the capsid gene and the 3' untranslated region of one ANV isolate being transferred to another ANV. These results reveal that infection of chicken flocks with multiple ANV isolates is common and this needs to be taken into consideration in diagnosis of ANV using molecular techniques and in future epidemiological investigations. PMID- 26365396 TI - Biosimilar monoclonal antibodies: the scientific basis for extrapolation. AB - INTRODUCTION: Biosimilars are biologic products that receive authorization based on an abbreviated regulatory application containing comparative quality and nonclinical and clinical data that demonstrate similarity to a licensed biologic product. Extrapolation of safety and efficacy has emerged as an important way to simplify biosimilar development. Regulatory authorities have generally reached the consensus that extrapolation of similarity from one indication to other approved indications of the reference product can be permitted if it is scientifically justified. AREAS COVERED: Recently, the first biosimilar, biosimilar infliximab (Remsima/Inflectra) to the innovator monoclonal antibody infliximab (Remicade), was approved in the European Union, Canada and South Korea; the USA subsequently approved its first biosimilar, a less complex molecule (filgrastim-sndz). Based on two clinical trials of biosimilar infliximab in patients with rheumatoid arthritis and ankylosing spondylitis, the European Medicines Agency allowed extrapolation to all eight approved indications for innovator infliximab, whereas Health Canada did not permit extrapolation to the indications for ulcerative colitis and Crohn's disease. These differing decisions on extrapolation of indications for biosimilar infliximab highlight important unanswered regulatory and scientific questions. Here, we propose substantive scientific considerations for indication extrapolation. EXPERT OPINION: The preclinical and clinical criteria that are currently required to merit indication extrapolation have not been rigorously evaluated. PMID- 26365397 TI - Design of novel non-contact multimedia controller for disability by using visual stimulus. AB - The design of a novel non-contact multimedia controller is proposed in this study. Nowadays, multimedia controllers are generally used by patients and nursing assistants in the hospital. Conventional multimedia controllers usually involve in manual operation or other physical movements. However, it is more difficult for the disabled patients to operate the conventional multimedia controller by themselves; they might totally depend on others. Different from other multimedia controllers, the proposed system provides a novel concept of controlling multimedia via visual stimuli, without manual operation. The disabled patients can easily operate the proposed multimedia system by focusing on the control icons of a visual stimulus device, where a commercial tablet is used as the visual stimulus device. Moreover, a wearable and wireless electroencephalogram (EEG) acquisition device is also designed and implemented to easily monitor the user's EEG signals in daily life. Finally, the proposed system has been validated. The experimental result shows that the proposed system can effectively measure and extract the EEG feature related to visual stimuli, and its information transfer rate is also good. Therefore, the proposed non-contact multimedia controller exactly provides a good prototype of novel multimedia controlling scheme. PMID- 26365398 TI - Cor triatriatum sinister: Is it less sinister in older patients? PMID- 26365399 TI - A complex procedure in the thoracic endovascular aortic repair era needs long term follow-up to compete. PMID- 26365400 TI - Late gastric conduit ischemia from celiac artery stenosis salvaged by stent therapy. PMID- 26365401 TI - Reversible but risky: Pulmonary hypertension in advanced heart failure is the Achilles' heel of cardiac transplantation. PMID- 26365402 TI - Possible pulmonary Rhizopus oryzae infection in a previously healthy child after a near-drowning incident. AB - This article reports on a previously healthy 17-month-old boy who developed pulmonary mucormycosis after a near-drowning incident in a goose pond. The patient survived without neurological sequelae and recovered, under treatment with amphotericin B, from the rare and often invasive fungal infection with Rhizopus spp., usually occurring in immunodeficient patients. PMID- 26365403 TI - Maximal force and tremor changes across the menstrual cycle. AB - PURPOSE: Sex hormones have profound effects on the nervous system in vitro and in vivo. The present study examines the effect of the menstrual cycle on maximal isometric force (MVC) and tremor during an endurance task. METHODS: Nine eumenorrheic females participated in five study visits across their menstrual cycle. In each menstrual phase, an MVC and an endurance task to failure were performed. Tremor across the endurance task was quantified as the coefficient of variation in force and was assessed in absolute time and relative percent time to task failure. RESULTS: MVC decreases 23% from ovulation to the mid luteal phase of the menstrual cycle. In absolute time, the mid luteal phase has the highest initial tremor, though the early follicular phase has substantially higher tremor than other phases after 150 s of task performance. In relative time, the mid luteal phase has the highest level of tremor throughout the endurance task. CONCLUSIONS: Both MVC and tremor during an endurance task are modified by the menstrual cycle. Performance of tasks and sports which require high force and steadiness to exhaustion may be decreased in the mid luteal phase compared to other menstrual phases. PMID- 26365404 TI - A feasibility study of multi-site,intracellular recordings from mammalian neurons by extracellular gold mushroom-shaped microelectrodes. AB - The development of multi-electrode array platforms for large scale recording of neurons is at the forefront of neuro-engineering research efforts. Recently we demonstrated, at the proof-of-concept level, a breakthrough neuron-microelectrode interface in which cultured Aplysia neurons tightly engulf gold mushroom-shaped microelectrodes (gMMUEs). While maintaining their extracellular position, the gMMUEs record synaptic- and action-potentials with characteristic features of intracellular recordings. Here we examined the feasibility of using gMMUEs for intracellular recordings from mammalian neurons. To that end we experimentally examined the innate size limits of cultured rat hippocampal neurons to engulf gMMUEs and measured the width of the "extracellular" cleft formed between the neurons and the gold surface. Using the experimental results we next analyzed the expected range of gMMUEs-neuron electrical coupling coefficients. We estimated that sufficient electrical coupling levels to record attenuated synaptic- and action-potentials can be reached using the gMMUE-neuron configuration. The definition of the engulfment limits of the gMMUEs caps diameter at <=2-2.5 MUm and the estimated electrical coupling coefficients from the simulations pave the way for rational development and application of the gMMUE based concept for in cell recordings from mammalian neurons. PMID- 26365406 TI - Opposing effects of ketamine and acetyl L-carnitine on the serotonergic system of zebrafish. AB - Ketamine, a pediatric anesthetic, is a noncompetitive N-methyl-D-aspartic acid (NMDA) receptor antagonist. Studies show that ketamine is neurotoxic in developing mammals and zebrafish. In both mammals and zebrafish, acetyl L carnitine (ALCAR) has been shown to be protective against ketamine toxicity. Ketamine is known to modulate the serotonergic system in mammals. Here, we measured the levels of serotonin (5-HT) and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA) in the embryos exposed to ketamine in the presence and absence of ALCAR. Ketamine, at lower doses, did not produce significant changes in the 5-HT or 5-HIAA levels in 3 dpf (day post-fertilization) embryos. However, 2 mM ketamine (internal embryo exposure levels comparable to human anesthetic plasma concentration) significantly reduced 5-HT level, and 5-HIAA was not detectable indicating that 5-HT metabolism was abolished. In the presence or absence of 2 mM ketamine, ALCAR by itself did not significantly alter 5-HT or 5-HIAA levels compared to the control. Ratios of metabolite/5-HT indicated that 2 mM ketamine inhibited 5-HT metabolism to 5-HIAA whereas lower doses (0.1-0.3 mM) of ketamine did not have any effect. ALCAR reversed the effects of 2 mM ketamine not only by restoring 5-HT and 5-HIAA levels but also 5-HT turnover rate to control levels. Whole mount immunohistochemical studies showed that 2 mM ketamine reduced the serotonergic area in the brain whereas ALCAR expanded it with increased axonal sprouting and branching. These results indicate that ketamine and ALCAR have opposing effects on the zebrafish serotonergic system. PMID- 26365407 TI - Decreased plasma levels of neureglin-1 in drug naive patients and chronic patients with schizophrenia. AB - Although the neuregulin-1 (NRG1) gene is one of the susceptibility genes for schizophrenia and various other psychiatric diseases, it remains unclear how individual psychiatric diseases affect the expression of the NRG1 protein in patients. A previous study reported a schizophrenia-linked decrease in serum NRG1 levels. The present study aimed to replicate this initial finding and to assess its disease specificity for schizophrenia. We collected plasma samples from drug naive patients with first-episode schizophrenia (n=80), patients with chronic schizophrenia (n=86), patients with bipolar I disorder (n=60), patients with bipolar II disorder (n=60) and patients with major depressive disorder (n=60), we measured the plasma levels of NRG1beta1 and compared the levels with those of age and sex-matched healthy volunteers (n=82). One-way ANOVA and post hoc analyses detected specific NRG1beta1 decreases in the participants with first-episode and chronic schizophrenia but not in those with bipolar I disorder, bipolar II disorder or major depressive disorder. The mean plasma levels of NRG1beta1 immunoreactivity were 4.27+/-0.71 ng/mL in the participants with first-episode schizophrenia, 4.08+/-0.64 ng/mL in the participants with chronic schizophrenia and 7.21+/-0.91 ng/mL in the healthy controls. Although we analyzed the pathological correlations of NRG1beta1 immunoreactivity in terms of the clinical parameters of the sample, we observed only weak positive correlations with the age of the participants with chronic schizophrenia and the disease onset times of the participants with bipolar II disorder. We failed to identify correlations between other clinical parameters and plasma NRG1beta1 immunoreactivity among all patient subjects. These findings suggest that NRG1 may serve as a relatively specific disease marker for schizophrenia. However, the pathological role of this decrease must be explored further. PMID- 26365408 TI - Hippocampal synaptotagmin-4 is correlated with impaired spatial learning and memory in SAMP8 mice. AB - The mechanism underlying age-related cognitive impairment remains unclear. To determine whether synaptotagmin (Syt)-1 and Syt-4 are involved in age-related cognitive impairment, we used a radial six-arm water maze (RAWM) to evaluate spatial learning and memory deficits in the senescence accelerated prone mouse 8. The Syt-1 and Syt-4 levels of different subregions of the dorsal hippocampus (DH) were detected through immunohistochemistry. The RAWM results revealed that 13- and 9-month-old mice exhibited longer latencies and more errors in both the learning and memory phases than 5-month-old mice. Similar results were observed in the comparison of 13-month-old mice to 9-month-old mice. Compared with the 9- and/or 5-month-old mice, the 13-month-old mice exhibited higher Syt-1 and Syt-4 levels in the majority of the DH subregions with the exception of Syt-1 in the dentate gyrus-hilus and Syt-4 in the dentate gyrus-hilus and cornu ammonis 1 pyramidal cell layer. With the exception of Syt-1 in the 9-month-old mice, the Syt-1 and Syt-4 levels in several DH subregions overall and in each group were significantly correlated with the performances on the RAWM. Therefore, the altered Syt-1 and Syt-4 levels in the different DH layers may have been involved in the impairments in spatial learning and memory during normal aging. PMID- 26365411 TI - Characterization of Clinical and Laboratory Profiles of the Deletional alpha2 Globin Gene Polyadenylation Signal Sequence (AATAAA > AATA- -) in an Indian Population. AB - alpha-Thalassemia (alpha-thal) is characterized by large deletions involving the variable regions of alpha2 and/or alpha1 genes. Nondeletional mutations and polyadenylation (polyA) signal sequence motif mutations are less common. In this retrospective study, we describe a fragment length analysis-based polymerase chain reaction (PCR) assay for screening the T(Indian) (AATAAA > AATA- -; HBA2: c.*93_*94delAA) polyA signal deletion along with its clinical and laboratory presentation in 21 patients. Most of the patients were diagnosed in early adulthood with a clinical presentation ranging from asymptomatic in the heterozygous state to severe Hb H disease with a prominent hemolytic component in the homozygous state. On genetic analysis, 14 patients were found to be homozygotes, five were compound heterozygotes and two were heterozygotes. Thus, the T(Indian) polyA signal deletion is common in the Indian population and should be screened for in patients with nondeletional alpha-thal mutations. PMID- 26365409 TI - Flupirtine effectively prevents development of acute neonatal seizures in an animal model of global hypoxia. AB - Current first-line drugs for the treatment of neonatal seizures have limited efficacy and are associated with side effects. Uncontrolled seizures may exacerbate brain injury and contribute to later-life neurological disability. Therefore, it is critical to develop a treatment for neonatal seizures that is effective and safe. In early-life, when the gamma-aminobutyric acid (GABA) inhibitory system is not fully developed, potassium channels play an important role in controlling excitability. An earlier study demonstrated that flupirtine, a KCNQ potassium channel opener, is more efficacious than diazepam and phenobarbital for the treatment of chemoconvulsant-induced neonatal seizures. In newborns, seizures are most commonly associated with hypoxic-ischemic encephalopathy (HIE). Thus, in the present study, we examined the efficacy of flupirtine to treat neonatal seizures in an animal model of global hypoxia. Our results showed that flupirtine dose dependently blocks the occurrence of behavioral seizures in pups during hypoxia. Additionally, flupirtine inhibits the development of hypoxia-induced clinical seizures and associated epileptiform discharges, as well as purely electrographic (subclinical) seizures. These results suggest that flupirtine is an effective anti-seizure drug, and that further studies should be conducted to determine the time window within which it's administration can effectively treat neonatal seizures. PMID- 26365412 TI - A Tubing-Free Microfluidic Wound Healing Assay Enabling the Quantification of Vascular Smooth Muscle Cell Migration. AB - This paper presents a tubing-free microfluidic wound healing assay to quantify the migration of vascular smooth muscle cells (VSMCs), where gravity was used to generate a laminar flow within microfluidic channels, enabling cell seeding, culture, and wound generation. As the first systemic study to quantify the migration of VSMCs within microfluidic environments, the effects of channel geometries, surface modifications and chemokines on cellular migration were investigated, revealing that 1) height of the micro channels had a significant impact on cell migration; 2) the surface coating of collagen induced more migration of VSMCs than fibronectin coated surfaces and 3) platelet derived growth factor resulted in maximal cell migration compared to tumor necrosis factor alpha and fetal bovine serum. Furthermore, migrations of five types of VSMCs (e.g., the human vascular smooth muscle cell line, two types of primary vascular smooth cells, and VSMCs isolated from two human samples) were quantified, finding that VSMCs from the cell line and human samples demonstrated comparable migration distances, which were significantly lower than the migration distances of two primary cell types. As a platform technology, this wound healing assay may function as a new model to study migration of VSMCs within microfluidic environments. PMID- 26365413 TI - Controversy about UK assisted dying bill. PMID- 26365414 TI - International Liver Cancer Association Annual Conference. PMID- 26365415 TI - MRI study identifies three subtypes of glioblastoma. PMID- 26365417 TI - US Government targets "natural" cigarette marketing claims. PMID- 26365416 TI - Genome-wide linkage analyses of non-Hispanic white families identify novel loci for familial late-onset Alzheimer's disease. AB - INTRODUCTION: Few high penetrance variants that explain risk in late-onset Alzheimer's disease (LOAD) families have been found. METHODS: We performed genome wide linkage and identity-by-descent (IBD) analyses on 41 non-Hispanic white families exhibiting likely dominant inheritance of LOAD, and having no mutations at known familial Alzheimer's disease (AD) loci, and a low burden of APOE epsilon4 alleles. RESULTS: Two-point parametric linkage analysis identified 14 significantly linked regions, including three novel linkage regions for LOAD (5q32, 11q12.2-11q14.1, and 14q13.3), one of which replicates a genome-wide association LOAD locus, the MS4A6A-MS4A4E gene cluster at 11q12.2. Five of the 14 regions (3q25.31, 4q34.1, 8q22.3, 11q12.2-14.1, and 19q13.41) are supported by strong multipoint results (logarithm of odds [LOD*] >=1.5). Nonparametric multipoint analyses produced an additional significant locus at 14q32.2 (LOD* = 4.18). The 1-LOD confidence interval for this region contains one gene, C14orf177, and the microRNA Mir_320, whereas IBD analyses implicates an additional gene BCL11B, a regulator of brain-derived neurotrophic signaling, a pathway associated with pathogenesis of several neurodegenerative diseases. DISCUSSION: Examination of these regions after whole-genome sequencing may identify highly penetrant variants for familial LOAD. PMID- 26365418 TI - Giant aortic aneurysm in a child with Takayasu arteritis. AB - Takayasu arteritis is a chronic, idiopathic, granulomatous vasculitis involving the aorta, its major branches, and occasionally the pulmonary arteries. Although rare in children, it is the third most common vasculitis in the paediatric population. Although aneurysmal disease has been reported in adults with Takayasu arteritis, it is a rare entity in children. We present the case of a 10-year-old boy with a giant ascending and arch aneurysm that necessitated follow-up surgery for a new aneurysm and occlusive disease. This is also the first published case involving endovascular aortic graft placement for the management of vascular sequela of Takayasu arteritis in a child. PMID- 26365419 TI - Simultaneous Analysis of Tertiary Butylhydroquinone and 2-tert-Butyl-1,4 benzoquinone in Edible Oils by Normal-Phase High-Performance Liquid Chromatography. AB - During the process of antioxidation of tertiary butylhydroquinone (TBHQ) in oil and fat systems, 2-tert-butyl-1,4-benzoquinone (TQ) can be formed. The toxicity of TQ was much more than that of TBHQ. In the work, a normal-phase high performance liquid chromatography (NP-HPLC) method for the accurate and simultaneous detection of TBHQ and TQ in edible oils was investigated. A C18 column was used to separate TBHQ and TQ, and the gradient elution solutions consisted of n-hexane containing 5% ethyl acetate and n-hexane containing 5% isopropanol. The ultraviolet (UV) detector was set at dual wavelength mode (280 nm for TBHQ and 310 nm for TQ). The column temperature was 30 degrees C. Before the NP-HPLC analysis, TBHQ and TQ were first extracted by methanol, subjected to vortex treatment, and then filtered through a 0.45 MUm membrane filter. Results showed that linear ranges of TBHQ and TQ were both within 0.10-500.00 MUg/mL (R(2) > 0.9999). The limit of detection (LOD) and limit of quantification (LOQ) of TBHQ and TQ were below 0.30 and 0.91 MUg/mL and below 0.10 and 0.30 MUg/mL, respectively. The recoveries of TBHQ and TQ were 98.92-102.34 and 96.28-100.58% for soybean oil and 96.11-99.42 and 98.83-99.24% for lard, respectively. These results showed that NP-HPLC can be successfully used to analyze simultaneously TBHQ and TQ in the oils and fats. PMID- 26365420 TI - The genetics of alcohol dependence: Twin and SNP-based heritability, and genome wide association study based on AUDIT scores. AB - Alcohol dependence (AD) is among the most common and costly public health problems contributing to morbidity and mortality throughout the world. In this study, we investigate the genetic basis of AD in a Dutch population using data from the Netherlands Twin Register (NTR) and the Netherlands Study of Depression and Anxiety (NESDA). The presence of AD was ascertained via the Alcohol Use Disorders Identification Test (AUDIT) applying cut-offs with good specificity and sensitivity in identifying those at risk for AD. Twin-based heritability of AD AUDIT was estimated using structural equation modeling of data in 7,694 MZ and DZ twin pairs. Variance in AD-AUDIT explained by all SNPs was estimated with genome wide complex trait analysis (GCTA). A genome-wide association study (GWAS) was performed in 7,842 subjects. GWAS SNP effect concordance analysis was performed between our GWAS and a recent AD GWAS using DSM-IV diagnosis. The twin-based heritability of AD-AUDIT was estimated at 60% (55-69%). GCTA showed that common SNPs jointly capture 33% (SE = 0.12, P = 0.002) of this heritability. In the GWAS, the top hits were positioned within four regions (4q31.1, 2p16.1, 6q25.1, 7p14.1) with the strongest association detected for rs55768019 (P = 7.58 * 10(-7) ). This first GWAS of AD using the AUDIT measure found results consistent with previous genetic studies using DSM diagnosis: concordance in heritability estimates and direction of SNPs effect and overlap with top hits from previous GWAS. Thus, the use of appropriate questionnaires may represent cost-effective strategies to phenotype samples in large-scale biobanks or other population-based datasets. PMID- 26365421 TI - Modulation of single-molecule magnet behaviour via photochemical [2+2] cycloaddition. AB - The first example of phototunable SMMs has been reported. Upon UV irradiation, variations of the coordination sphere around Dy(III) ions actually affect the magnetic behaviour of the compound via [2+2] cycloaddition reaction, leading to a magnetic transformation from the SMM behaviour to a field-induced slow relaxation. PMID- 26365422 TI - Equalization enhanced phase noise in Nyquist-spaced superchannel transmission systems using multi-channel digital back-propagation. AB - Superchannel transmission spaced at the symbol rate, known as Nyquist spacing, has been demonstrated for effectively maximizing the optical communication channel capacity and spectral efficiency. However, the achievable capacity and reach of transmission systems using advanced modulation formats are affected by fibre nonlinearities and equalization enhanced phase noise (EEPN). Fibre nonlinearities can be effectively compensated using digital back-propagation (DBP). However EEPN which arises from the interaction between laser phase noise and dispersion cannot be efficiently mitigated, and can significantly degrade the performance of transmission systems. Here we report the first investigation of the origin and the impact of EEPN in Nyquist-spaced superchannel system, employing electronic dispersion compensation (EDC) and multi-channel DBP (MC DBP). Analysis was carried out in a Nyquist-spaced 9-channel 32-Gbaud DP-64QAM transmission system. Results confirm that EEPN significantly degrades the performance of all sub-channels of the superchannel system and that the distortions are more severe for the outer sub-channels, both using EDC and MC DBP. It is also found that the origin of EEPN depends on the relative position between the carrier phase recovery module and the EDC (or MC-DBP) module. Considering EEPN, diverse coding techniques and modulation formats have to be applied for optimizing different sub-channels in superchannel systems. PMID- 26365423 TI - Mid-infrared spectroscopic investigation of the perfect vitrification of poly(ethylene glycol) aqueous solutions. AB - Crystallization/recrystallization behaviors of poly(ethylene glycol) (PEG) aqueous solutions with water contents (WC's) of ~36-51 wt % were investigated by temperature-variable mid-infrared spectroscopy. At a WC of 43.2 wt %, crystallization and recrystallization of water and PEG were not observed. At this specific WC value (WCPV), perfect vitrification occurred. Below and above the WCPV value, crystallization/recrystallization behaviors changed drastically. The crystallization temperature below WCPV (237 K) was ~10 K greater than that above WCPV (226 K). Recrystallization above and below WCPV occurred in one (213 K) and two (198 and 210 K) steps, respectively. These findings resulted from the difference in the (re)crystallization behaviors of water molecules associated with PEG chains with helical and random-coil conformations. These two types of water molecules might have limiting concentrations for their (re)crystallization, indicating that perfect vitrification might have occurred when the concentrations of the two types of water molecules were less than the limiting concentrations of their (re)crystallization. PMID- 26365424 TI - Efficiency of biological therapies in patients with moderate to severe psoriasis: impact of a pharmacotherapeutic protocol. AB - BACKGROUND: It is not clear how to best use biologics in the treatment of psoriasis. Our objective was to assess use of a protocol for biological therapies (BT) in psoriasis. METHODS: A consensus protocol was established that included the indications for BT and dose optimization. Patient's characteristics, effectiveness, and cost of BT were analyzed before and after the implementation with two cross-sectional studies to assess its impact. RESULTS: About 106 were treated before the protocol and 118 patients were treated after. After implementing the protocol, the dose was reduced in 43.4% of the patients receiving adalimumab, in 37.5% for etanercept, in 28.6% for infliximab, and in 14.7% for ustekinumab. No statistically significant differences were found in PASI score after the implementation of the protocol, except for the percentage of patients that achieved PASI 75 with ustekinumab, which was slightly higher. The global yearly savings achieved with the protocol implementation were 115,969 ?. CONCLUSIONS: The protocol helped to increase the efficiency of BT, with decreasing doses of BT without affecting treatment effectiveness. PMID- 26365425 TI - Risk of selected gastrointestinal toxicities in cancer patients treated with MEK inhibitors: a comparative systematic review and meta-analysis. AB - We performed a systematic review and meta-analysis of the risk of gastrointestinal (GI) toxicities associated with MEK inhibitors. Eligible studies included randomized Phase II and III trials of cancer patients on the three MEK inhibitors (trametinib, selumetinib and cobimetinib), describing events of stomatitis, diarrhea and vomiting. Our search strategy yielded 250 potentially relevant citations from Pubmed/Medline, Google scholar and CENTRAL Cochrane registry. After exclusion of ineligible studies, a total of 16 clinical trials were considered eligible for the meta-analysis. The relative risks of all-grade stomatitis, diarrhea and vomiting were 2.03 (95% CI 1.41-2.96; p = 0.002), 1.92 (95% CI 1.48-2.50; p < 0.00001) and 1.35 (95% CI 1.06-1.71; p = 0.01). Subgroup analyses according to agent used (trametinib vs Selumetinib), the regimen used (monotherapy vs combination) and the cancer treated (melanoma vs nonmelanoma) did not reveal any significant difference between the subgroups. Our meta-analysis has demonstrated that MEK inhibitor-based treatment is associated with an increased risk of stomatitis, diarrhea and vomiting compared to control. Clinicians should be aware of this risk and perform regular assessment. PMID- 26365426 TI - Left Bundle Branch Block Negatively Affects Coronary Flow Velocity Reserve and Myocardial Contractile Reserve in Nonischemic Dilated Cardiomyopathy. AB - BACKGROUND: Coronary flow velocity reserve (CFVR) of the left anterior descending coronary artery (LAD) and myocardial contractile reserve are often impaired in nonischemic dilated cardiomyopathy (DCM). Whether they are affected by the presence of left bundle branch block (LBBB) remains unaddressed. The aim of the study was to investigate how LBBB influences CFVR of the LAD and myocardial contractile reserve in patients with DCM. METHODS: One hundred eighty-one patients with DCM (116 men; mean age, 63 +/- 12 years) underwent high-dose dipyridamole (0.84 mg/kg over 6 min) stress echocardiography with CFVR evaluation of the LAD by Doppler. All patients had ejection fractions < 40% (mean, 31 +/- 8%) and angiographically normal or near normal coronary arteries. CFVR was defined as the ratio between hyperemic peak and basal peak diastolic coronary flow velocities. CFVR > 2.0 was considered normal. Inotropic reserve was defined as rest-stress variation in wall motion score index >= 0.20. This was a prospective analysis of an unselected sample consecutively enrolled and retrospectively selected. RESULTS: The study group was separated on the basis of presence (n = 122) or absence (n = 59) of LBBB. Patients with LBBB were older (64 +/- 11 vs 59 +/- 12 years, P = .004) and had reduced resting ejection fractions (30 +/- 9% vs 33 +/- 7%, P = .02), CFVR of the LAD (1.96 +/- 0.41 vs 2.23 +/- 0.73, P = .001), and myocardial contractile reserve (variation in wall motion score index, -0.18 +/- 0.17 vs -0.33 +/- 0.28; P < .001). On multivariate logistic regression analysis, resting ejection fraction (hazard ratio [HR], 1.15; 95% CI, 1.03-1.29; P = .01), smoking habit (HR, 2.63; 95% CI, 1.23-5.62; P = .01), and LBBB (HR, 2.29; 95% CI, 1.05-5.04; P = .04) were independently associated with reduced CFVR, while restrictive transmitral pattern (HR, 2.56; 95% CI, 1.18-5.55; P = .02), end-diastolic volume (HR, 0.98; 95% CI, 0.67-0.99; P = .02), and LBBB (HR, 2.20; 95% CI, 1.11-4.34; P = .02) independently predicted reduced myocardial contractile reserve. CONCLUSIONS: CFVR during vasodilator stress echocardiography is a suitable tool for assessing microvascular dysfunction in routine clinical practice. Patients with DCM and LBBB show more severe forms of microvascular dysfunction, which is related to worse left ventricular function and lack of contractile reserve. Therapeutic interventions to restore microvascular function may improve left ventricular function parameters in patients with DCM. PMID- 26365428 TI - Lead, cadmium and organochlorine pesticide residues in hunted red deer and wild boar from northern Italy. AB - The objectives of the present study were to assess heavy metal cadmium (Cd), lead (Pb) and organochlorine pesticide concentrations in tissues of red deer (Cervus elaphus) and wild boar (Sus scrofa) from nine hunting areas and to evaluate related risk factors for the host animal. Over a period of 2 years, a total of 1055 and 210 masseters, 424 and 201 livers, 642 and 152 kidneys were collected from wild boar and red deer, respectively, and concentrations of Cd, Pb and organochlorine pesticides were determined. Comparing the two species, Cd concentration in the kidney (3.72 mg/kg), liver (0.67 mg/kg) and muscle (0.02 mg/kg) of wild boar was found to be significantly higher than in the organs of red deer (1.02 mg/kg in the kidneys, 0.07 mg/kg in the liver and 0.006 mg/kg in muscle). Mean Pb concentrations were found to be similar in both animals, with 0.39, 0.52 and 2.60 mg/kg detected in the wild boar kidney, liver and muscle, respectively, and 0.24, 0.21 and 2.04 mg/kg in the respective organs of the red deer. No difference in concentrations were found based on age class, location of tissue sample or contaminant in the case of wild boar. By contrast, a significantly lower Cd concentration was found in the kidney of the young red deer. The search for organochlorine pesticides in both red deer and wild boar produced negative results with values below the limits of detection. Due to the high levels of renal Cd and muscle Pb detected in wild boar and red deer, further research needs to be carried out in an effort to identify the source of contamination and preserve the health of animals and humans. PMID- 26365429 TI - Ethnic differences in adverse drug reactions to asthma medications: a systematic review. AB - BACKGROUND: Information on ethnic diversity of adverse drug reactions (ADRs) to asthma medications is rare despite evidence suggesting higher risk for African Americans when using beta2-adrenergic receptor agonists. The objectives are to investigate how ethnic background was involved in ADR assessment and to examine the relationship between ethnic background and ADRs to asthma medications. METHODS: MEDLINE was searched until March 2014. All types of studies reporting ADRs to asthma medications involving more than one ethnic group were included. Extracted information includes study designs, ethnic backgrounds, intervention, and types and severities of ADRs. RESULTS: Among the selected 15 randomised clinical trials, six pooled analyses of randomized clinical trials, and five prospective observational studies, only six studies compared ADRs across different ethnic groups. The majority of the comparisons were either statistically insignificant or inconclusive. CONCLUSIONS: Ethnicity was largely overlooked. Most studies neglected to report ADRs by ethnicity. Lack of consistency in defining ethnicities complicated further pooled analyses. Despite the higher prevalence of asthma among specific ethnic minority groups, few studies disaggregated information by ethnic background, and reports of ADRs to asthma medications in different ethnic groups were rare. We suggest that the inclusion of ADR analysis by different ethnic backgrounds is desirable. PMID- 26365427 TI - GITR subverts Foxp3(+) Tregs to boost Th9 immunity through regulation of histone acetylation. AB - Glucocorticoid-induced TNFR-related protein (GITR) is a costimulatory molecule with diverse effects on effector T cells and regulatory T cells (Tregs), but the underlying mechanism remains poorly defined. Here we demonstrate that GITR ligation subverts the induction of Foxp3(+) Tregs and directs the activated CD4(+) T cells to Th9 cells. Such GITR-mediated iTreg to Th9 induction enhances anti-tumour immunity in vivo. Mechanistically, GITR upregulates the NF-kappaB family member p50, which recruits histone deacetylases to the Foxp3 locus to produce a 'closed' chromatin structure. Furthermore, GITR ligation also activates STAT6, and STAT6 renders Il9 locus accessible via recruitment of histone acetyltransferase p300, and together with inhibition of Foxp3, GITR induces strong Th9 responses. Thus, Th9 cells and iTregs are developmentally linked and GITR can subvert tolerogenic conditions to boost Th9 immunity. PMID- 26365430 TI - High-dose circumferential chemodenervation of the internal anal sphincter: A new treatment modality for uncomplicated chronic anal fissure: A retrospective cohort study (with video). AB - BACKGROUND: Botulinum toxin injection into the internal anal sphincter is gaining popularity as a second line therapy for chronic anal fissures if medical therapy fails. The dosage of botulinum toxin reported ranged from 20 to 50 IU with no more than 3 injection sites and results in a healing rate of 41%-88% at 3 months. We propose a new injection method of high-dose circumferential chemodenervation of 100 IU in treating chronic anal fissure. METHODS: This was a retrospective review at a single academic center. 75 patients (50 women and 25 men) with uncomplicated chronic anal fissures underwent high-dose circumferential chemodenervation-internal anal sphincter (100 IU). We measured fissure healing, complication, and recurrence rates at 3 and 6 months post injection. RESULTS: Of the 75 patients, healing rate was 90.7% at 3 months follow up with the first injection and 81.3% with the second injection. The recurrence rates were 20.6% and 12.5% at 6 months after the 1st and 2nd injections respectively. Excluding 5 patients who lost follow up, the total healing rate of the study cohort was 100%. At 2 weeks and 3 months, there were no major complications including hematoma, infection, flatus, fecal, and urinary incontinence. CONCLUSIONS: High-dose circumferential chemodenervation-internal anal sphincter (100 IU) is a safe and effective method for uncomplicated chronic anal fissure. PMID- 26365431 TI - Complications and outcomes after early surgical treatment for poor-grade ruptured intracranial aneurysms: A multicenter retrospective cohort. AB - INTRODUCTION: Early surgical treatment has been proposed to improve outcomes of selected patients with poor-grade ruptured intracranial aneurysms. We performed a multicenter retrospective analysis to identify complications and outcomes after early surgery. METHODS: We analyzed data from the two cohorts of patients with poor-grade ruptured aneurysms. Poor-grade aneurysm was defined as a World Federation of Neurosurgical Society (WFNS) grade of IV or V after resuscitation. Early surgery was defined as surgery performed within 72 h after poor-grade condition. RESULTS: Of the 144 patients who underwent surgical treatment for poor grade aneurysm, 80 underwent early surgery and were included in this report. Forty-one (51%) patients presented with a WFNS grade of IV and 39 (49%) presented with a WFNS grade of V. Cerebral infarction occurred in 17 (21%) patients and was the most common complication except for pneumonia. No patients had a good outcome after postoperative aneurysm rebleeding. At follow-up (mean 12.6 months), 37 (46%) patients had a good outcome after early surgery. Multivariate analysis showed that a WFNS grade of V, presence of intraventricular hemorrhage, brain herniation were independent predictors of poor outcome after early surgery. Patients with WFNS grade V more often had a poor outcome after postoperative cerebral infarction, rebleeding or symptomatic vasospasm. CONCLUSIONS: Patients with a WFNS grade of V, intraventricular hemorrhage, brain herniation were more likely to have a poor outcome after early surgery. Postoperative complications, including rebleeding and cerebral infraction, should be prevented and treated aggressively to maximize the chance of good outcome in poor-grade patients. PMID- 26365433 TI - Cyclometalated (boroxinato)gold(III) complexes from arrested transmetalation. AB - Organic boroxines are ubiquitous, but metallaboroxine analogues remain rare. A new class of (boroxinato)gold species are demonstrated here, as are observations of phosphorescence from boroxinato complexes. Four new compounds are crystallographically characterized. PMID- 26365432 TI - PLZF-Induced Upregulation of CXCR4 Promotes Dairy Goat Male Germline Stem Cell Proliferation by Targeting Mir146a. AB - Previous studies have shown that promyelocytic leukemia zinc finger (PLZF), chemokine (C-X-C motif) receptor 4 (CXCR4) and mir146a were associated with the self-renewal of mouse spermatogonial stem cells (SSCs); however, there is little information on their effects on the fate of livestock SSCs. Here, we have identified a regulatory pathway in dairy goat mGSCs, involving PLZF, mir146a and the SDF-1 receptor CXCR4. PLZF overexpression downregulated mir146a and simultaneously upregulated the expression of CXCR4 protein, whereas PLZF knockdown (siPLZF) induced the specifically opposite effects. The in vitro assays demonstrated that PLZF specifically interacts with and suppresses the mir146a promoter, and mir146a targets CXCR4 to impede its translation. The levels of ERK1/2 phosphorylation in the mGSCs overexpressed CXCR4 and PLZF were upregulated, respectively, whereas mir146a expression was decreased and CXCR4 protein was increased. Mir146a overexpression and siPLZF impaired mGSC proliferation and differentiation, however, Mir146a knockdown induced the opposite effects. The effects of PLZF and mir146a were mediated regulation by mir146a and CXCR4, respectively. Overexpression of CXCR4 or addition of CXCL12 in cultures of dairy goat mGSCs resulted in the upregulation of their signaling, and the phosphorylation of ERK1/2 was increased. Collectively, these findings indicate that PLZF is an important transcription factor in the regulation of the expression of CXCR4 to promote dairy goat mGSC proliferation by targeting mir146a. PMID- 26365434 TI - Effect of parenterally L-arginine supplementation on the respiratory distress syndrome in preterm newborns. AB - L-Arginine (L-Arg) is the precursor of nitric oxide which plays an important role on pulmonary circulation and pulmonary vascular tone. Earlier studies suggested that L-Arg levels in preterm newborns with respiratory distress syndrome (RDS) were low due to its consumption and L-Arg supplementation may reduce the severity of RDS. Our aim was detect the effect of the parenterally L-Arg supplementation on RDS severity. The subjects were chosen between preterm newborns (gestational age <34 weeks) (n = 30). Twenty of the subjects were diagnosed with permaturity and RDS, and 10 of the subjects were healthy preterm newborns. Ten of the subjects was taken L-Arg (1.5 mmol/kg/d) in addition to routine RDS treatment and assumed as "Group 1". In this group, daily L-Arg supplementation was started end of the first day, and continued at end of fifth day. The others of the subjects diagnosed with RDS was take routine RDS treatment and assumed as "Group 2". Healthy preterm newborns assumed as "Group 3". Blood collections for L-Arg levels via tandem mass spectrometry were made in first day and repeated on the seventh days. Oxygenation index was used to determine severity of RDS. L-Arg consentrations in Group 1 were 8.7 +/- 4.1 MUM/L and 11.9 +/- 5.0 MUM/L in first and seventh day, respectively. L-Arg consentrations were 12.6 +/- 4.5 MUM/Land 10.9 +/- 5.4 MUM/L in Group 2 and 8.6 +/- 5.1 MUM/L and 9.4 +/- 4.1 MUM/L in Group 3. There is no correlation between L-Arg concentrations and OI also duration of the mechanical ventilation of the subjects in patient groups (Group 1 and 2). PMID- 26365435 TI - Structure of HCMV glycoprotein B in the postfusion conformation bound to a neutralizing human antibody. AB - Human cytomegalovirus (HCMV) poses a significant threat to immunocompromised individuals and neonates infected in utero. Glycoprotein B (gB), the herpesvirus fusion protein, is a target for neutralizing antibodies and a vaccine candidate due to its indispensable role in infection. Here we show the crystal structure of the HCMV gB ectodomain bound to the Fab fragment of 1G2, a neutralizing human monoclonal antibody isolated from a seropositive subject. The gB/1G2 interaction is dominated by aromatic residues in the 1G2 heavy chain CDR3 protruding into a hydrophobic cleft in the gB antigenic domain 5 (AD-5). Structural analysis and comparison with HSV gB suggest the location of additional neutralizing antibody binding sites on HCMV gB. Finally, immunoprecipitation experiments reveal that 1G2 can bind to HCMV virion gB suggesting that its epitope is exposed and accessible on the virus surface. Our data will support the development of vaccines and therapeutic antibodies against HCMV infection. PMID- 26365436 TI - Clinician descriptions of communication strategies to improve treatment engagement by racial/ethnic minorities in mental health services: A systematic review. AB - OBJECTIVE: To describe studies on clinician communication and the engagement of racial/ethnic minority patients in mental health treatment. METHODS: Authors conducted electronic searches of published and grey literature databases from inception to November 2014, forward citation analyses, and backward bibliographic sampling of included articles. Included studies reported original data on clinician communication strategies to improve minority treatment engagement, defined as initiating, participating, and continuing services. RESULTS: Twenty three studies met inclusion criteria. Low treatment initiation and high treatment discontinuation were related to patient views that the mental health system did not address their understandings of illness, care or stigma. Treatment participation was based more on clinician language use, communication style, and discussions of patient-clinician differences. CONCLUSION: Clinicians may improve treatment initiation and continuation by incorporating patient views of illness into treatment and targeting stigma. Clinicians may improve treatment participation by using simple language, tailoring communication to patient preferences, discussing differences, and demonstrating positive affect. PRACTICE IMPLICATIONS: Lack of knowledge about the mental health system and somatic symptoms may delay treatment initiation. Discussions of clinician backgrounds, power, and communication style may improve treatment participation. Treatment continuation may improve if clinicians tailor communication and treatment plans congruent with patient expectations. PMID- 26365437 TI - Donor miR-196a-2 polymorphism is associated with hepatocellular carcinoma recurrence after liver transplantation in a Han Chinese population. AB - Recurrence of hepatocellular carcinoma (HCC) is one of the leading causes of death after liver transplantation (LT). We aim to evaluate the association of donor and recipient single nucleotide polymorphisms (SNPs) with the risk of HCC recurrence after LT. A total of 155 adult patients who underwent primary LT for HCC were enrolled. Ten SNPs associated with HCC susceptibility were genotyped. Patients who received donor livers with the rs11614913 homozygous CC variant presented significantly higher recurrence rates of HCC (41.7 vs. 15.3%, p = 0.009) and lower cumulative tumor-free survival (p = 0.005) than those who received TT wild-type donor livers. The donor rs11614913 genetic variant was an independent risk factor for HCC recurrence (odds ratio = 2 per each C allele, p < 0.05) and could significantly improve the predictive abilities of clinical models (Milan, UCSF and Hangzhou criteria). Donor livers homozygous for rs11614913 CC were associated with a higher miR-196a expression than TT (p = 0.002). In a lentiviral infection of mouse liver and orthotopic mouse model of HCC, the liver miR-196a overexpression group showed a significantly larger tumor size than the control group (p = 0.001). There is a close association between the tumor size and expression of miR-196a in the liver (r = 0.693, p = 0.001). In conclusion, the donor miR-196a-2 rs11614913 polymorphism is associated with HCC recurrence after LT and improves the predictive value of clinical models. The overexpression of miR-196a in the liver might provide a tumor-favorable environment for the development of HCC. PMID- 26365439 TI - Quantitative Electron-Excited X-Ray Microanalysis of Borides, Carbides, Nitrides, Oxides, and Fluorides with Scanning Electron Microscopy/Silicon Drift Detector Energy-Dispersive Spectrometry (SEM/SDD-EDS) and NIST DTSA-II. AB - A scanning electron microscope with a silicon drift detector energy-dispersive X ray spectrometer (SEM/SDD-EDS) was used to analyze materials containing the low atomic number elements B, C, N, O, and F achieving a high degree of accuracy. Nearly all results fell well within an uncertainty envelope of +/-5% relative (where relative uncertainty (%)=[(measured-ideal)/ideal]*100%). Quantification was performed with the standards-based "k-ratio" method with matrix corrections calculated based on the Pouchou and Pichoir expression for the ionization depth distribution function, as implemented in the NIST DTSA-II EDS software platform. The analytical strategy that was followed involved collection of high count (>2.5 million counts from 100 eV to the incident beam energy) spectra measured with a conservative input count rate that restricted the deadtime to ~10% to minimize coincidence effects. Standards employed included pure elements and simple compounds. A 10 keV beam was employed to excite the K- and L-shell X-rays of intermediate and high atomic number elements with excitation energies above 3 keV, e.g., the Fe K-family, while a 5 keV beam was used for analyses of elements with excitation energies below 3 keV, e.g., the Mo L-family. PMID- 26365438 TI - Diagnostic Value of Selected Echocardiographic Variables to Identify Pulmonary Hypertension in Dogs with Myxomatous Mitral Valve Disease. AB - BACKGROUND: Pulmonary hypertension (PH) is commonly associated with myxomatous mitral valve disease (MMVD). Because dogs with PH present without measureable tricuspid regurgitation (TR), it would be useful to investigate echocardiographic variables that can identify PH. AIM: To investigate associations between estimated systolic TR pressure gradient (TRPG) and dog characteristics and selected echocardiographic variables. ANIMALS: 156 privately owned dogs. MATERIALS AND METHODS: Prospective observational study comparing the estimations of TRPG with dog characteristics and selected echocardiographic variables in dogs with MMVD and measureable TR. RESULTS: Tricuspid regurgitation pressure gradient was significantly (P < .05) associated with body weight corrected right (RVIDDn) and left (LVIDDn) ventricular end-diastolic and systolic (LVIDSn) internal diameters, pulmonary arterial (PA) acceleration to deceleration time ratio (AT/DT), heart rate, left atrial to aortic root ratio (LA/Ao), and the presence of congestive heart failure. Four variables remained significant in the multiple regression analysis with TRPG as a dependent variable: modeled as linear variables LA/Ao (P < .0001) and RVIDDn (P = .041), modeled as second order polynomial variables: AT/DT (P = .0039) and LVIDDn (P < .0001) The adjusted R(2) value for the final model was 0.45 and receiver operating characteristic curve analysis suggested the model's performance to predict PH, defined as 36, 45, and 55 mmHg as fair (area under the curve [AUC] = 0.80), good (AUC = 0.86), and excellent (AUC = 0.92), respectively. CONCLUSION AND CLINICAL IMPORTANCE: In dogs with MMVD, the presence of PH might be suspected with the combination of decreased PA AT/DT, increased RVIDDn and LA/Ao, and a small or great LVIDDn. PMID- 26365440 TI - Synthesizing Ag Nanoparticles of Small Size on a Hierarchical Porosity Support for the Carboxylative Cyclization of Propargyl Alcohols with CO2 under Ambient Conditions. AB - Both immobilization of Ag nanoparticles (AgNPs) of very small size on hierarchical porosity supports and carboxylative cyclization of propargyl alcohols with CO2 under ambient conditions are very interesting. In this work, we synthesized AgNPs supported on sulfonated macroreticular resin (SMR) with hierarchical pores in water/alcohol solutions. It was shown that the size of the AgNPs on the SMR could be tailored easily by altering the synthetic solutions, and very small AgNPs with narrow size distribution (1-3 nm) could be obtained in water/methanol solution. It was found that the AgNPs/SMR with small AgNPs was highly efficient and an easily recyclable catalyst for the synthesis of alpha alkylidene cyclic carbonates by carboxylative cyclization of propargyl alcohols with CO2 at ambient pressure and temperature, which was the first work to use metal nanoparticles as the catalysts for the reaction. PMID- 26365441 TI - The superparamagnetic iron oxide tracer: a valid alternative in sentinel node biopsy for breast cancer treatment. AB - The European Union has determined that from 2016 breast cancer patients should be treated in Specialist Breast Units that achieve the minimum standards for the mandatory quality indicators as defined by Eusoma. The existing standard for axillary lymph node staging in breast cancer is sentinel node biopsy (SNB), performed using Technetium-sulphur colloid (99m Tc) alone or with blue dye. The major limits of radioisotope consist in the problems linked to radioactivity, in the shortage of tracer and nuclear medicine units. Among existing alternative tracers, SentiMag(r) , which uses superparamagnetic iron oxide particles, can represent a valid option for SNB. We conducted a paired, prospective, multicentre study to evaluate the non-inferiority of SentiMag(r) vs. 99m Tc. The primary end point was the detection rate (DR) per patient. The study sample consists of 193 women affected by breast carcinoma with negative axillary assessment. The concordance rate per patients between 99m Tc and SentiMag(r) was 97.9%. The DR per patient was 99.0% for 99m Tc and 97.9% for SentiMag(r) . SentiMag(r) appears to be non-inferior to the radiotracer and safe. While 99m Tc remains the standard, SentiMag(r) DR appears adequate after a minimum learning curve. In health care settings where nuclear medicine units are not available, SentiMag/Sienna+(r) allows effective treatment of breast cancer patients. PMID- 26365442 TI - An evaluation system for financial compensation in traditional Chinese medicine services. AB - OBJECTIVES: To describe the major factors influencing financial compensation in traditional Chinese medicine (TCM) and prioritize what TCM services should be compensated for. DESIGN AND SETTING: Two structured questionnaires-a TCM service baseline questionnaire and a service cost questionnaire-were used to collect information from TCM public hospitals on TCM services provided in certain situations and service cost accounting. The cross-sectional study examined 110 TCM services provided in four county TCM public hospitals in Shandong province. From the questionnaire data, a screening index system was established via expert consultation and brainstorming. Comprehensive evaluation of TCM services was performed using the analytic hierarchy process method. MAIN OUTCOME MEASURES: Weighted coefficients were used to measure the importance of each criterion, after which comprehensive evaluation scores for each service were ranked to indicate what services should receive priority for financial compensation. RESULTS: Economy value, social value, and efficacy value were the three main criteria for screening for what TCM services should be compensated for. The economy value local weight had the highest value (0.588), of which the profit sub criterion (0.278) was the most important for TCM financial compensation. Moxibustion was tied for the highest comprehensive evaluation scores, at 0.65 while Acupuncture and Massage Therapy were tied for the second and third highest, with 0.63 and 0.58, respectively. CONCLUSIONS: Government and policymakers should consider offer financial compensation to Moxibustion, Acupuncture, Massage Therapy, and TCM Orthopedics as priority services. In the meanwhile, it is essential to correct the unreasonable pricing, explore compensation methods, objects and payment, and revise and improve the accounting system for the costs of TCM services. PMID- 26365443 TI - Efficacy of a Chinese herbal medicine for the treatment of atopic dermatitis: a randomised controlled study. AB - BACKGROUND: More randomised control trials are required to assess the efficacy of traditional Chinese medicine. This multi-centre, randomised, assessor-blind, controlled study assessed the efficacy of the Chinese herbal formula Pei Tu Qing Xin Tang (PTQXT) for treating patients with atopic dermatitis (AD). METHODS: Patients aged 5-25 years with moderate-to-severe AD were randomised to receive a 12-week treatment involving either oral administration of PTQXT; oral administration of PTQXT combined with an external application of Chinese herbs; or oral administration of antihistamine and a placebo of PTQXT pills added to topical 1% mometasone furoate. The primary end-point measure was the change in the Scoring Atopic Dermatitis Index (SCORAD) at the end of the observation period, and secondary end-points included quality of life (QOL). The outcomes were evaluated at baseline, then every 4 weeks from week 4 to week 12 and every 8 weeks from week 12 to week 36. RESULTS: Two hundred and seventy-five patients were recruited. During the 12-week treatment period, up to the primary end-point, the mean SCORAD decreased gradually in all three groups. At week 28 and week 36, there was a significantly greater decrease in the mean SCORAD for the Chinese herbal medicine-treated groups than for the control group (at week 28, P=0.002 and P=0.036, respectively; at week 36, P<0.001 and P=0.002, respectively). At week 36, the difference in QOL scores showed a significantly greater improvement in both Chinese herbal medicine-treated groups than in the control group (P<0.001 and P<0.001, respectively). CONCLUSIONS: PTQXT is effective in decreasing the severity of the disease and improving the QOL in patients with moderate-to-severe AD. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR-TRC-08000156. PMID- 26365444 TI - Alteration of delta-6-desaturase (FADS2), secretory phospholipase-A2 (sPLA2) enzymes by Hot-nature diet with co-supplemented hemp seed, evening primrose oils intervention in multiple sclerosis patients. AB - BACKGROUND: The effect of nutrition and dietary supplements as environmental factors has been suggested as possible factors affecting both disease risk and progression in on the course of multiple sclerosis with complex genetic-risk profiles. This study was aimed to assess regulation of surface-membrane enzymes such as Delta-6-desaturase (FADS2), secretory Phospholipase A2(sPLA2) by hemp seed and evening primrose oils as well as Hot-natured dietary intervention in relapsing remitting multiple sclerosis (RRMS) patients. METHODS AND MATERIALS: In this double blind, randomized trial, 100 RRMS patients with Extended disability status score (EDSS)<6 were allocated into 3 groups: "Group A" who received co supplemented hemp seed and evening primrose oils along with advised Hot nature diet; "Group B", who received olive oil; "Group C", who received the co supplemented oils. Clinically EDSS and functional score as well as biochemical parameters [blood cells polyunsaturated fatty acid (PUFA), FADS2, sPLA2] were assessed at baseline and after 6 months. RESULTS: Mean follow-up was 180+/-2.9SD days (N=65, 23 M and 42 F aged 34.25+/-8.07 years with disease duration 6.80+/ 4.33 years). There was no significant difference in studies parameters at baseline. After 6 months, significant improvements in EDSS and functional score were found in the groups A and C while EDSS and pyramidal score showed significant increase in group B. Alteration of biochemical parameters showed improvement in groups A and C whereas there was worsening condition for group B after the intervention. CONCLUSION: The co-supplemented hemp seed and evening primrose oils with Hot nature diet can have beneficial effects in improving clinical symptoms and signs in RRMS patients which were confirmed by regulation of surface-membrane enzymes. PMID- 26365445 TI - Acupuncture lowers blood pressure in mild hypertension patients: a randomized, controlled, assessor-blinded pilot trial. AB - OBJECTIVES: To preliminarily assess the effects of acupuncture on prehypertension and stage I hypertension, and to provide data for further research. DESIGN: A randomized, controlled, assessor-blinded study with an 8-week intervention period and a 4-week follow-up. INTERVENTIONS: Participants were patients with systolic blood pressure (SBP) of 120-159mmHg or diastolic blood pressure (DBP) of 80 99mmHg.Thirty participants were allocated to acupuncture group or untreated control group at a 1:1 ratio. The acupuncture group received standard acupuncture twice weekly for 8 weeks, and was followed-up for 4 weeks after treatment; the control group did not receive any type of anti-hypertensive treatment for 12 weeks. MAIN OUTCOME MEASURES: Primary outcome measure was SBP and DBP at post treatment. The secondary outcomes were SBP and DBP at follow-up; Euro Quality of life (EQ-5D), heart rate variability (HRV), body mass index (BMI), and blood lipid profile. RESULTS: DBP (-5.7mmHg; P=0.025), but not SBP (-6.0mmHg; P=0.123), was significantly different between groups at post-treatment. Both DBP (-7.8mmHg; P=0.004) and SBP (-8.6mmHg; P=0.031) were significantly different at follow-up. Among the HRV indices, only high frequency power was significantly different between groups at weeks 4 and 8 (P=0.047 and P=0.030, respectively). There were no differences between groups in EQ-5D, BMI or lipid profile. CONCLUSION: The results of this study show that acupuncture might lower blood pressure in prehypertension and stage I hypertension, and further RCT need 97 participants in each group. The effect of acupuncture on prehypertension and mild hypertension should be confirmed in larger studies. TRIAL REGISTRATION: KCT0000496. PMID- 26365446 TI - Association between use of self-prescribed complementary and alternative medicine and menopause-related symptoms: a cross-sectional study. AB - OBJECTIVES: To examine the association between self-prescribed complementary and alternative medicine use and menopause-related symptoms, stratified by menopausal status. METHODS: Data were obtained from a cross-sectional survey of a nationally representative sample of 10,011 menopausal women from the Australian Longitudinal Study on Women's Health, conducted in 2010. Multivariable logistic regression models were applied to identify if the use of selected self-prescribed complementary and alternative medicine was significantly associated with a range of menopause-related symptoms. RESULTS: Vitamins/minerals were more likely to be used by natural menopausal women experiencing anxiety (adjusted OR=1.20) and/or stiff/painful joints (adjusted OR=1.16). Yoga/meditation was more likely to be used by women with hysterectomy (adjusted OR=1.76) or natural menopausal women (adjusted OR=1.38) experiencing anxiety. Herbal medicines were more likely to be used by natural menopausal women experiencing anxiety (adjusted OR=1.22), tiredness (adjusted OR=1.20), and/or stiff/painful joints (adjusted OR=1.17), and by women with oophorectomy experiencing tiredness (adjusted OR=1.45). Aromatherapy oils were more likely to be used by natural menopausal women experiencing night sweats (adjusted OR=1.25) and by women with hysterectomy experiencing anxiety (adjusted OR=2.02). Chinese medicines were more likely to be used by women with oophorectomy experiencing stiff/painful joints (adjusted OR=4.06) and/or palpitations (adjusted OR=3.06). CONCLUSIONS: Our study will help improve the patient-provider communication regarding complementary and alternative medicine use for menopause, and we conclude that menopausal status should be taken into account by providers for menopause care. The women's experience and motivations of such use warrant further research. PMID- 26365447 TI - Comparison between herbal medicine and fluoxetine for depression: a systematic review of randomized controlled trials. AB - OBJECTIVE: To evaluate the effectiveness and safety of Chinese herbal medicine (CHM) versus fluoxetine on depression. DESIGN: A systematic review of randomized controlled trials (RCTs). METHODS: RCT with two parallel groups that compared CHM and fluoxetine on treatment of depression with reported decreased Hamilton Depression Scale (HAMD) and adverse events during treatment were included after searching through six electric-databases. The methodological quality of RCTs was assessed according to the Cochrane risk of bias tool. Meta-analysis was conducted using RevMan 5.3 software with pooled mean difference (MD) or risk ratio (RR) and their 95% confidence interval (CI) if no significant heterogeneity was detected. A SOF table was generated using GRADEPro software to evaluate the overall quality of the evidence. RESULTS: Twenty-six trials with 3294 participants were included in the review. Most of them had high risk of bias during conducting and reporting. The results achieved weak evidence which showed CHM had similar effect to fluoxetine (20mg/day) on relieving depression according to HAMD assessment (for primary depression: MD=-0.08, 95%CI -0.98-0.82; for secondary depression: MD=-0.36, 95%CI -1.55-0.83), but fewer incidences of adverse events than the drug (for primary depression: RR=0.31, 95%CI 0.17-0.59; for post-stroke depression: RR=0.04, 95%CI 0.00-0.25). No serious adverse event was found in neither CHM nor fluoxetine group. CONCLUSIONS: Due to the poor quality of included trials and the potential publication bias of this review, no confirmed conclusion could be draw to evaluate the effectiveness and safety of CHM for depression compared with fluoxetine. PMID- 26365448 TI - A randomised, controlled, single-blinded study on the impact of a single rhythmical massage (anthroposophic medicine) on well-being and salivary cortisol in healthy adults. AB - BACKGROUND: Rhythmical massage (RM) has evolved from classical massage and is based on the principles of Anthroposophic medicine. The goal of this randomized, single-blinded study was to assess the efficacy of a single RM intervention with either aroma oil (RA) or a neutral oil (RM) compared to a sham massage (SM) on several dimensions of well-being and salivary cortisol in a laboratory setting. METHODS: 118 healthy adults (mean age: 25.2 years; SD: 4.7) were randomized to one of three groups (RM, RA or SM). After baseline measurements, all subjects were exposed to an experimental stressful situation (Trier Social Stress Test, TSST), before receiving a single massage intervention of about 60 min including a 20-minute rest period. Well-being as the main outcome parameter was assessed by standardized questionnaires (MDBF, Bf-S, B-L) and visual analogue scales (VAS) prior to the beginning of the massage and subsequently. Salivary cortisol and heart rate variability (data are shown elsewhere) were also measured. RESULTS: Participants who received RM or RA showed no statistically significant improvements (MDBF, Bf-S, B-L) compared to the SM group after adjusting for baseline differences observed between the treatment groups. Furthermore, no statistically significant differences were found between the RM and RA groups in any of the analyses. Within a follow-up survey all participants from the RA and 82% from the RM group described the intervention as "relaxing" compared with 42% in the SM group. Salivary cortisol did not differ statistically significantly between the three groups over time. CONCLUSIONS: We found no significant effect within this trial. This may be due to the methodological complexity of massage research and especially the sham-controlled design with only one single intervention examined. The influence of the setting, and the expectations of and interaction between participant and practitioner seem to play a role that needs to be verified. Therefore the true potential of rhythmical massage intervention still needs to be validated. PMID- 26365449 TI - Efficacy of Tongkat Ali (Eurycoma longifolia) on erectile function improvement: systematic review and meta-analysis of randomized controlled trials. AB - OBJECTIVE: To determine the efficacy of Tongkat Ali (Eurycoma longifolia) herbal extract on erectile function improvement. METHODS: Comprehensive electronic databases were searched from inception through October 2014. Randomized controlled trials investigating Tongkat Ali compared to placebo were included. Outcome of interest was the improvement of erectile dysfunction. The difference of changes from baseline of the outcome between Tongkat Ali and placebo was pooled using weighted mean difference (WMD). Methodological quality of included studies was assessed using Jadad's quality scale and Cochrane's risk of bias. RESULTS: Of the 342 articles identified, 2 studies involving a total of 139 participants were analyzed. No significance between group difference was found in the mean WMD of the change in the 5- item version of the international index of erectile function (IIEF-5) at week-12 (0.91; 95% CI: -1.50 to 3.33 with I(2)=89.5%, P-value=0.002) with statistical heterogeneity. Based on the subgroup analysis, significant improved IIEF-5 score of 2.15 (95% CI 1.03-3.27) was found in subjects with lower baseline IIEF-5 score, but this was not seen among those with higher baseline IIEF-5 score. CONCLUSION: Based on current evidence, the herbal extract of Tongkat Ali may have clinical effect on erectile function. However, more efficacy trials are warranted to further support current evidence. PMID- 26365450 TI - A longitudinal analysis of self-prescribed complementary and alternative medicine use by a nationally representative sample of 19,783 Australian women, 2006-2010. AB - BACKGROUND: Complementary and alternative medicine (CAM) use is increasingly popular amongst general populations around the world with women constituting substantial CAM users. However, self-prescribed CAM use does raise potential safety concerns and so it is important to identify those risk factors associated with self-prescribed CAM use. METHODS: Data was obtained from the Australian Longitudinal Study on Women's Health (ALSWH). Longitudinal data analyses were conducted on questionnaire data from the 1973-78 cohort (n=9,145) and the 1946-51 cohort (n=10,638), collected over the period 2006-2010. RESULTS: In the 1973-78 cohort, use of self-prescribed CAM was 73.2% in 2006 and 75.3% in 2009. For the 1946-51 cohort, use of self-prescribed CAM was 73.9% in 2007 and 74.7% in 2010. There were similar levels of use of individual self-prescribed CAM, with the exception that the use of herbal medicine was much higher among the 1946-51 cohort (20% vs. 27%). There was a substantial increase over three years in the use of vitamins/minerals in both cohorts (21% and 19%, respectively). In contrast, there was a considerable decline over three years in use of aromatherapy oils in both cohorts (34% and 28%, respectively). CONCLUSION: Self prescribed CAM use is popular amongst women in Australia and it is important that conventional practitioners providing women's health care be cognizant of such use amongst their patients. In order to ensure effective practice, there is a need for further research to explore women's decision-making and experiences around self-prescribed CAM use. PMID- 26365451 TI - TCM tongue diagnosis index of early-stage breast cancer. AB - OBJECTIVES: This paper investigates discriminating tongue features to distinguish between early stage breast cancer (BC) patients and non-breast cancer individuals through non-invasive traditional Chinese medicine (TCM) tongue diagnosis. DESIGN: The tongue features for 67 patients with 0 and 1 stages of BC, and 70 non-breast cancer individuals are extracted by the automatic tongue diagnosis system (ATDS). A total of nine tongue features, namely, tongue color, tongue quality, tongue fissure, tongue fur, red dot, ecchymosis, tooth mark, saliva, and tongue shape are identified for each tongue. Features extracted are further sub-divided according to the areas located, i.e., spleen-stomach, liver-gall-left, liver-gall right, kidney, and heart-lung areas. This study focuses on deriving significant tongue features (p<0.05) to discriminate early-stage BC patients from non-breast cancer individuals. RESULTS: The Mann-Whitney test shows that the amount of tongue fur (p=0.024), maximum covering area of tongue fur (p=0.009), thin tongue fur (p=0.009), the average area of red dot (p=0.049), the maximum area of red dot (p=0.009), red dot in the spleen-stomach area (p=0.000), and red dot in the heart lung area (p=0.000) demonstrate significant differences. The data collected are further classified into two groups. The training group consists of 57 early-stage BC patients and 60 non-breast cancer individuals, while the testing group is composed of 10 early-stage BC patients and 10 non-breast cancer individuals. The logistic regression by utilizing these 7 tongue features with significant differences in Mann-Whitney test as factors is performed. In order to reduce the number of tongue features employed in prediction, tongue features with the least amount of significant difference, namely, maximum area of red dot and average area of red dot, are removed progressively. The tongue features of the testing group are employed in the aforementioned three models to test the power of significant tongue features identified in predicting early-stage BC. An accuracy of 80%, 80% and 90% is reached on non-breast cancer individuals by applying the 7, 6 and 5 significant tongue features obtained through Mann-Whitney test, respectively, while 60%, 60% and 50% is reached on the corresponding early-stage BC patients. CONCLUSION: The TCM tongue diagnosis can serve as a preliminary screening procedure in the early detection of BC in light of its simple and non invasive nature, followed by other more accurate testing process. To the best of our knowledge, this is the first attempt in applying non-invasive TCM tongue diagnosis to the discrimination of early-stage BC patients and non-breast cancer individuals. PMID- 26365452 TI - Effects of music therapy on pain, anxiety, and vital signs in patients after thoracic surgery. AB - OBJECTIVE: To examine the effectiveness of music listening on pain, anxiety, and vital signs among patients after thoracic surgery in China. DESIGN AND SETTING: A randomized controlled clinical trial was conducted in the thoracic surgery department of two tertiary hospitals in Wuhan, China. 112 patients were recruited and randomly assigned to either experimental (n=56) or control (n=56) group respectively. INTERVENTION: The experimental group received standard care and a 30-min soft music intervention for 3 days, while the control group received only standard care. Measures include pain, anxiety, vital signs (blood pressure, heart rate and respiratory rate), patient controlled analgesia, and diclofenac sodium suppository use. RESULTS: The experimental group showed statistically significant decrease in pain, anxiety, systolic blood pressure and heart rate over time compared to the control group, but no significant difference were identified in diastolic blood pressure, respiratory rate, patient controlled analgesia and diclofenac sodium suppository use. CONCLUSION: The findings provide further evidence to support the practice of music therapy to reduce postoperative pain and anxiety, and lower systolic blood pressure and heart rate in patients after thoracic surgery in China. PMID- 26365453 TI - Hypnotherapy for insomnia: a systematic review and meta-analysis of randomized controlled trials. AB - OBJECTIVE: To examine the efficacy and safety of hypnotherapy for insomnia as compared to placebo, pharmacological or non-pharmacological intervention, or no treatment. METHODS: A systematic search on major electronic databases was conducted up until March 2014. Inclusion criteria are: (1) randomized controlled trials (RCTs) or quasi-RCTs; (2) intervention targeted at improving sleep; (3) hypnosis as an intervention; and (4) English language articles. Sleep diary variable is the primary outcome measure. RESULTS: Six RCTs of hypnotherapy and seven on autogenic training or guided imagery, comprising 502 subjects, were included. Eleven of the 13 studies had low methodological quality, as indicated by a modified Jadad score below 3, and high risks of bias in blinding and design of the control interventions. No adverse events related to hypnosis were reported, though seldom investigated. Meta-analyses found hypnotherapy significantly shortened sleep latency compared to waitlist (standardized mean difference, SMD=-0.88, 95% confidence interval (CI): -1.56, -0.19, P=0.01, I(2)=15%), but no difference compared to sham intervention (SMD: -1.08, 95% CI: 3.15, 0.09, P=0.31, I(2)=90%). Similar results were found for autogenic training or guided imagery (SMD with waitlist=-1.16, 95% CI: -1.92, -0.40, P=0.003, I(2)=0%; SMD with sham intervention=-0.50, 95% CI: -1.19, 0.19, P=0.15, I(2)=0%). CONCLUSIONS: Generalizability of the positive results is doubtful due to the relatively small sample size and methodological limitations. Future studies with larger sample size and better study design and methodology are called for. PMID- 26365454 TI - Music versus lifestyle on the autonomic nervous system of prehypertensives and hypertensives--a randomized control trial. AB - OBJECTIVES: Ragas of Indian music are said to be beneficial in normalizing blood pressure (BP). The objective of this study was to evaluate the effect of passive listening to relaxing raga on the autonomic functions of hypertensives and prehypertensives and provide scientific evidence. METHODS: Ethical clearance was obtained from the institutional review board. A prospective, randomized controlled trial was done on hundred prehypertensives/stage I hypertensives, randomly divided into two groups (n=50 in each). Group 1 received music intervention along with lifestyle modifications while Group 2 received only lifestyle modifications (according to Joint national committee VII guidelines). Group 1 listened to raga bhimpalas played on flute for 15min daily for at least 5 days/week for 3 months. The main outcome measures were heart rate variability (HRV) (Power lab 15T, AD Instruments), BP and stress levels (State Trait anxiety inventory score). All HRV variables were log transformed for analysis. Statistical analysis was done using SPSS version 18.0 with P<0.05 being considered statistically significant. RESULTS: Group 1 exhibited significant reduction in stress levels, diastolic BP and systolic BP decreased in Group 2 after intervention. Insignificant rise in parasympathetic parameters of HRV (SDNN, RMSSD, HF ms(2), HF nu) was seen after intervention in both the groups. We found significantly increased parasympathetic and lower sympathetic parameters (LF ms(2), LF nu, LF/HF) in Group 1 and 2 males and females of Group 2. The results suggest that females of Group 1 were least compliant with the given intervention. CONCLUSIONS: Passive listening to Indian music along with conventional lifestyle modifications has a role in normalizing BP through autonomic function modification and thus can be used as a complementary therapy along with other lifestyle modifications. PMID- 26365455 TI - Chinese herbal medicine for Henoch-Schonlein purpura in children without renal damage: a systematic review of randomized controlled trials. AB - BACKGROUND: Henoch-Schonlein Purpura (HSP) is the most common necrotizing vasculitis affecting children. Traditional Chinese herbal medicine (CHM) was widely used. We aim to explore the evidence of effectiveness and safety of CHM for HSP in children without renal damage. METHODS: Randomized controlled trials (RCTs) comparing CHM with conventional medications were searched from five databases. Eligible data were pooled using random-effects model using RevMan 5.2 Subgroup analysis for different co-interventions and sensitivity analysis for reducing heterogeneity were implemented. GRADE approach was adopted. RESULTS: We included 15 trials with 1112HSP children (age 1-16 years old), disease duration one day to three months. The overall methodological quality of included trials is relatively low. Adjunctive oral CHM treatments reduced renal damage (6 trials, RR 0.47, 95%CI 0.31-0.72, I(2)=0%), and subsiding time (days) of purpura (5 trials, mean difference (MD) -3.60, 95%CI -4.21 to -2.99, I(2)=23%), joint pain (5 trials, MD -1.04, 95%CI -1.33 to -0.74, I(2)=1%) and abdomen pain (5 trials, MD 1.69, 95%CI -2.51 to -0.86, I(2)=74%). Subgroup and sensitivity analysis did not change the direction of results. No severe adverse events reported. CONCLUSIONS: Orally taken adjunctive CHM treatments are effective for children suffering HSP in terms of reducing renal damage and subsiding time of purpura, and could possibly reduce subsiding pain of joint and abdomen. No reliable conclusion regarding safety is possible based on the safety data retrieved. Further rigorous trials are warranted. PMID- 26365456 TI - The FVB/N mice: A well suited strain to study learning and memory processes using olfactory cues. AB - The FVB/N mice are well suited to generate transgenic animals. These mice are also particularly sensitive to seizures and neurodegeneration induced by systemic administration of chemoconvulsants and are very useful to model epilepsy. However, previous studies report strong cognitive and visual impairments suggesting this background unsuitable for behavioral analysis. In this study, we assessed and compared learning abilities of FVB/N mice to the well characterized C57BL/6 strain using the olfactory tubing maze, a non-visual hippocampus dependent task in which the mice were trained to learn odor-reward associations. Exploratory behavior and spontaneous locomotor activity were then compared using the open field test. We demonstrated that FVB/N mice were able to learn the task, reaching at the end of the test a high percentage of correct responses. Interestingly, the performance of the FVB/N mice was at least similar to that of the C57BL/6 mice. Moreover, in contrast to previous reports, the FVB/N mice displayed a spontaneous locomotor activity lower than C57BL/6 mice. Our study demonstrated that FVB/N mice are not cognitively impaired and that their learning and memory performance can be assessed when the task is based on olfaction rather than vision. PMID- 26365458 TI - Impairment of intradimensional shift in an attentional set-shifting task in rats with chronic bilateral common carotid artery occlusion. AB - Studies of rats with chronic bilateral common carotid artery occlusion (BCCAo), an animal model for vascular dementia (VaD), have reported hippocampus-dependent memory impairment and associated neuropathologies. Patients with VaD also experience attentional shifting dysfunction. However, animal models of VaD have not been used to study attentional function. Therefore, the present study examined attentional function in rats with BCCAo, using attentional set-shifting task (ASST) that required rats to choose a food-baited pot from 2 possible pots. ASST included 6 consecutive sessions including simple discrimination, compound discrimination, intradimensional shifting, extradimensional shifting, and reversals. The BCCAo rats were significantly slower at learning the intradimensional set-shifting task compared to control rats. Previous studies have demonstrated that the cingulate cortex and medial prefrontal cortex are critical to intradimensional and extradimensional set-shifting, respectively. Additionally, inflammatory responses and neuronal dysfunction were observed in rats with chronic BCCAo. In addition, OX-6 positive microglia significantly increased in the forceps minor white matter of BCCAo rats, and glutamate decarboxylase signals co-localized with NeuN were reduced in the anterior cingulate cortex of BCCAo rats, compared to control rats. Impaired neuronal and GABAergic neuronal integrity in the anterior cingulate cortex, damage to white matter, and attentional impairments observed in BCCAo rats suggest dysfunction of brain structures that are associated with attentional impairments observed in patients with VaD. PMID- 26365457 TI - Effects of varenicline on operant self-administration of alcohol and/or nicotine in a rat model of co-abuse. AB - Alcohol and nicotine (in the form of tobacco) are often taken together, with increased negative health consequences. Co-use may modify intake of one or both of the drugs, or the effects of drugs used to treat nicotine or alcohol addiction. Varenicline is commonly prescribed as an aid to enhance quitting smoking. More recently it has been shown to reduce alcohol intake in humans and laboratory animals. There is little work investigating the role of co-exposure to alcohol and nicotine in the effects of varenicline. In pilot clinical studies, it has been reported that smoking enhances varenicline's effectiveness as a treatment for alcohol misuse, but this relationship has not been systematically investigated. To help resolve this, we examined if the effects of varenicline on alcohol and nicotine self-administration (SA) in rats are modified when the two drugs are taken together. Rats were trained on alcohol SA, and some were implanted with i.v. catheters for nicotine SA. Groups of animals then lever pressed for alcohol or nicotine alone, and another group lever pressed for alcohol and nicotine, using a two lever choice procedure. Varenicline did not affect alcohol SA. Varenicline reduced nicotine SA modestly. Access to both alcohol and nicotine reduced self-administration of either drug, but did not change the effects of varenicline. We found that in rats with a history of alcohol SA, varenicline reduced reinstatement of extinguished alcohol seeking induced by exposure to an alcohol prime combined with cues previously associated with alcohol. PMID- 26365459 TI - A family-focused intervention for heart failure self-care: conceptual underpinnings of a culturally appropriate intervention. AB - AIM: A discussion of the conceptual elements of an intervention tailored to the needs of Lebanese families. BACKGROUND: The role of informal caregiving is strongly recommended for individuals with chronic conditions including heart failure. Although this importance is recognized, conceptual and theoretical underpinnings are not well elucidated nor are methods of intervention implementation. DESIGN: Discussion paper on the conceptual underpinning of the FAMILY model. METHODS AND DATA SOURCES: This intervention was undertaken using linked methods: (1) Appraisal of theoretical model; (2) review of systematic reviews on educational interventions promoting self-management in chronic conditions in four databases with no year limit; (3) socio-cultural context identification from selected papers; (4) expert consultation using consensus methods; and (5) model development. RESULTS: Theories on self-care and behavioural change, eighteen systematic reviews on educational interventions and selected papers identifying sociocultural elements along with expert opinion were used to guide the development of The FAMILY Intervention Heart Failure Model. Theory and practice driven concepts identified include: behavioural change, linkage, partnership and self-regulation. IMPLICATIONS FOR NURSING: Heart failure is a common condition often requiring in-hospital and home-based care. Educational interventions targeting the socio-cultural influences of the patients and their family caregivers through a structured and well-designed program can improve outcomes. CONCLUSION: As the burden of chronic diseases increases globally, particularly in emerging economies, developing models of intervention that are appropriate to both the individual and the socio-cultural context are necessary. PMID- 26365460 TI - Effects of chronic fluoxetine treatment on anxious behaviour of BALB/c mice in a 3-dimensional maze. AB - Here we used a 3-dimensional (3D) maze, a modification of the radial maze, to assess the effects of treatment for two weeks with a single daily dose of fluoxetine (20 mg/kg, i.p.) on anxiety in male BALB/c mice. We examined whether anxiolytic effects of fluoxetine can be detected over three daily test sessions. We examined also whether repeated handling associated with chronic treatment interferes with effects of fluoxetine on anxiety responses. The 3D maze comprises nine arms, each connected to an upward inclined bridge radiating from a central platform. In this maze, BALB/c mice cross frequently into the bridges but avoid the arms. This avoidance is used as an index of anxiety. Two separate groups received once a day either saline (SALCH, n = 8) or fluoxetine (FLUCH, n = 8) for 14 days, and up to 30 min before the test during the subsequent 3 days. A third group received saline (SALAC, n = 8) 30 min before the test, once a day for 3 days. SALAC mice did not cross into the arms, and continued this avoidance over 3 sessions. SALCH mice avoided the arms in session 1 whereas FLUCH mice did cross into the arms, and like SALCH mice, increased number of crossings into and time on the arms in subsequent sessions. Fluoxetine evidently had an anxiolytic effect but only in the first session. These results indicate that handling experience decreased fear and anxiety in the mice, which may have masked the anxiolytic effect of fluoxetine in the second and third test sessions. PMID- 26365461 TI - Single-Fluorophore Detection in Femtoliter Droplets Generated by Flow Focusing. AB - Aqueous microdroplets with a volume of a few femtoliters are an ideal sample size for single-molecule fluorescence experiments. In particular, they enable prolonged measurements to be made on individual molecules that can diffuse freely in the surrounding medium. However, the rapid production of monodisperse droplets in a hydrodynamic flow, such as microfluidic flow focusing, will often involve volumes that are typically too large (>0.5 pL) for single-molecule studies. Desired volumes of a few femtoliters, or smaller, can be produced by either tip streaming or step emulsification in a flow-focusing device; however, in both of these methods, the aqueous droplets are dispersed in a large volume of the continuous phase, where individual droplets can diffuse perpendicular to the flow direction, and the monodispersity of droplet size produced by tip streaming is difficult to sustain for more than transient time scales. We show here that the optimized design and fabrication of microfluidic devices with shallow channel depths can result in the reliable production of stable droplets of a few femtoliters at a high rate in the dripping regime of flow focusing. Furthermore, the generated microdroplets are localized in a two-dimensional plane to enable immediate analysis. We have demonstrated the fluorescence monitoring of single molecules of encapsulated green fluorescent protein. The apparatus is straightfoward, inexpensive, and readily assembled within an ordinary laboratory environment. PMID- 26365462 TI - Reduced muscle mitochondrial enzyme activity in MuSK-immunized mice. AB - AIM: Muscle specific kinase (MuSK) antibody-positive myasthenia gravis(MG) patients might present with clinical and electrophysiological signs of muscle atrophy. In this study, we investigated the potential contribution of mitochondrial dysfunction to muscle atrophy induced by MuSK immunity. METHODS: Mitochondrial enzyme expression was investigated in muscle samples of MuSK immunized, acetylcholine receptor (AChR)-immunized, and complete Freund's adjuvant (CFA)-immunized C57BL/6 (B6) mice using histochemical methods. Mitochondrial enzyme activity was also investigated in MuSK- and CFA-immunized mice. RESULTS: Histochemical analysis showed normal muscle fiber activity on succinate dehydrogenase (SDH) and cytochrome oxidase (COX) stains in all immunization groups. However, MuSK-immunized mice had more ragged-red fibers on modified Gomori-trichrome (MGT) stain and more pronounced type 1 muscle fiber atrophy. MuSK-immunized mice also showed reduced citrate synthase, SDH, and NADH cytochrome c-reductase activity. DISCUSSION: Our results suggest that MuSK immunity might induce muscle atrophy through mitochondrial dysfunction. PMID- 26365463 TI - Rare delayed brain metastasis from primary cutaneous adenoid cystic carcinoma. PMID- 26365464 TI - Fixation of skin biopsies for determination of epidermal nerve fiber density. PMID- 26365465 TI - Complications and Visual Outcomes After Secondary Intraocular Lens Implantation in Children. PMID- 26365466 TI - The zinc binding receptor GPR39 interacts with 5-HT1A and GalR1 to form dynamic heteroreceptor complexes with signaling diversity. AB - GPR39 is a class A G protein-coupled receptor involved in zinc binding and glucose homeostasis regulation, among other physiological processes. GPR39 was originally thought to be the receptor for obestatin peptide but this view has been challenged. However, activation of this receptor by zinc has been clearly established. Recent studies suggest that low GPR39 expression, due to deficient zinc levels, is involved in major depressive disorder. We have previously reported that zinc can alter receptor-receptor interactions and favor specific receptor interactions. In order to unravel the effect of zinc on specific G protein-coupled receptor association processes, we have performed FRET and co immunopurification studies with GPR39 and 5-HT1A and GalR1 which have been shown to dimerize. Our results suggest that zinc can modulate the formation of specific 5-HT1A-GPR39 and GalR1-5-HT1A-GPR39 heteroreceptor complexes under our experimental conditions. We have analyzed the differences in signaling between the mono-homomeric receptors 5-HT1A, GalR1 and GPR39 and the heteroreceptor complexes between them Our results show that the GPR39-5-HT1A heterocomplex has additive functionalities when compared to the monomeric-homomeric receptors upon receptor activation. In addition, the heterocomplex including also GalR1 shows a different behavior, upon exposure to the same agonists. Furthermore, these processes appear to be regulated by zinc. These findings provide a rationale for the antidepressive effect widely described for zinc because pro-depressive heterocomplexes are predominant at low zinc concentration levels. PMID- 26365467 TI - Effect of bevacizumab on intracranial meningiomas in patients with neurofibromatosis type 2 - a retrospective case series. AB - PURPOSE: The hallmark of neurofibromatosis type 2 (NF2) is bilateral vestibular schwannomas (VS). Approximately 80% of NF2 patients also have intracranial meningiomas. Vascular endothelial growth factor (VEGF) is expressed in both NF2 related and sporadic occurring meningiomas and anti-VEGF therapy (bevacizumab) may, therefore, be beneficial in NF2-related meningiomas. The purpose of the study was to report the effect of bevacizumab on meningiomas in NF2 patients. MATERIALS AND METHODS: We retrospectively reviewed the effect of bevacizumab on the cross-sectional area (CSA) of 14 intracranial meningiomas in 7 NF2 patients. Bevacizumab 10 mg/kg was administered intravenously every two weeks for six months and 15 mg/kg every three weeks thereafter. Patients were evaluated according to the modified Macdonald criteria with repeated magnetic resonance (MR) scans. RESULTS: The median duration of therapy was 27 months (range 16-34) and 42 MR scans (median 8, range 4-11) were reviewed. The median annual change in meningioma CSA prior to bevacizumab was 2% (range -4%-+76%). During treatment, a decrease in meningioma CSA was observed in 5 of 14 meningiomas (36%) in 5 of 7 patients (71%). The median decrease in CSA was -10% (range -3%--25%). One meningioma (7%) progressed and the remaining (93%) had stable disease. CONCLUSIONS: Bevacizumab may slow or reverse the growth of some NF-related meningiomas. However, we have previously reported a fatal case of intracerebral hemorrhage following bevacizumab in NF2 patients, wherefore, this effect needs to be balanced carefully against the risk of side effects. PMID- 26365468 TI - Proinflammatory role of the histamine H4 receptor in dextrane sodium sulfate induced acute colitis. AB - Millions of people worldwide are suffering from inflammatory bowel disease (IBD), which severely affects patients' life qualities and even life expectancies. The cause of the ailment is unknown and a profound understanding of the underlying pathogenetic mechanisms is still lacking. The biogenic amine histamine is one of several inflammatory mediators, to which a pathogenetic role in IBD has been attributed. Out of the four known histamine receptors, the histamine H4 receptor (H4R) has been demonstrated to act proinflammatory in experimental models of several inflammatory diseases. In order to evaluate a potential involvement of H4R in IBD we investigated the effect of genetic or pharmacological blockade of H4R-signaling in the model of dextran sodium sulfate (DSS)-induced colitis in mice. We analysed severity and progression of clinical signs of colitis, as well as histopathologic alterations in the colons and systemic or local cytokine concentrations. Both genetic deficiency and pharmacological blockade of H4R with the selective antagonist JNJ7777120 improved clinical and histological signs of colitis and dampened the inflammatory cytokine response. Our results indicate a proinflammatory role of histamine via H4R in IBD, thus extending the current pathophysiological understanding of IBD and demonstrating the therapeutic potential of selective H4R-antagonists for patients suffering from IBD. PMID- 26365469 TI - Estimation of body fluids with bioimpedance spectroscopy: state of the art methods and proposal of novel methods. AB - Determination of body fluids is a useful common practice in determination of disease mechanisms and treatments. Bioimpedance spectroscopy (BIS) methods are non-invasive, inexpensive and rapid alternatives to reference methods such as tracer dilution. However, they are indirect and their robustness and validity are unclear. In this article, state of the art methods are reviewed, their drawbacks identified and new methods are proposed. All methods were tested on a clinical database of patients receiving growth hormone replacement therapy. Results indicated that most BIS methods are similarly accurate (e.g. < 0.5 +/- 3.0% mean percentage difference for total body water) for estimation of body fluids. A new model for calculation is proposed that performs equally well for all fluid compartments (total body water, extra- and intracellular water). It is suggested that the main source of error in extracellular water estimation is due to anisotropy, in total body water estimation to the uncertainty associated with intracellular resistivity and in determination of intracellular water a combination of both. PMID- 26365470 TI - Physical activity training in US medical schools: Preparing future physicians to engage in primary prevention. AB - BACKGROUND: Medical professionals serve as influential sources of information and guidance for their patients. Medical school may be an opportune time to provide future physicians with training in physical activity (PA) so that it can be more effectively addressed in clinical practice. METHODS: To assess the inclusion and amount of PA training in US medical school curricula, we attempted to conduct structured interviews with the program directors of the 171 accredited US medical education programs in the spring of 2013. RESULTS: Seventy-four schools (allopathic, n = 64; osteopathic, n = 10) completed the structured interviews. Fifty-eight programs (78.4%) reported having PA training included as a part of their curriculum. Thirty-five (61.4%) and 25 (43.9%) programs included instruction on national aerobic and strength training guidelines, respectively. Thirty-one programs (56.4%) felt that they offered a sufficient level of PA related training for their students to successfully counsel their patients in the future. Over the 4 years of medical school, an average of 8.1 (+/- 9.8) h of mandatory PA training was offered. CONCLUSION: Though many medical schools report providing some level of PA content, the time dedicated for this training is still low in comparison to other topics, such as nutrition education, which are featured more prominently. New and innovative ideas are needed for the integration of more, higher quality PA training for our next generation of medical practitioners. PMID- 26365471 TI - Kin recognition or phenotype matching? PMID- 26365472 TI - Role of spiramycin in prevention of fetal toxoplasmosis. AB - OBJECTIVE: The aim of this study is to evaluate the efficacy of spiramycin in prevention of mother-to-child transmission of Toxoplasma gondii infection. METHODS: Patients within first trimester of their pregnancy with Toxoplasma IgM positivity (>0.65 index, ELISA, VIDAS) and IgG positivity (>8 IU/ml), who had low IgG avidity (<0.50 index, ELISA, Architet) were considered as having acute toxoplasmosis. These patients who had amniocentesis at the 19th-21st week of pregnancy were examined for the detection of Toxoplasma DNA. Detailed ultrasonographic examinations performed between the 20th and 24th gestational weeks and the mothers and babies were followed for at least one year. RESULTS: Out of 61 patients, 55 (90.2%) had received Spy prophylaxis while 6 (9.8%) cases refused Spy prophylaxis. Toxoplasma PCR test was found to be positive in amniotic fluid of 4 (6.6%) patients obtained by amniocentesis at the 19th-21st week of pregnancy. All four of these patients had refused Spy prophylaxis had positive Toxoplasma PCR in amniotic fluid (p < 0.01). CONCLUSION: Our results seem to encourage the use of spiramycin in women with toxoplasmosis during pregnancy. PMID- 26365473 TI - Defective SrTiO3 synthesized by arc-melting. AB - Defective perovskite SrTiO3 has been synthesized by rapid solidification of its melts obtained from arc-melting treatment. As a result of rich and stable defects implanted in SrTiO3, the bandgap was narrowed from 3.29 eV to 3.08 eV. Correspondingly, the defective SrTiO3 powders exhibit highly enhanced photocatalytic performance. PMID- 26365474 TI - Impact of platelet rich plasma and adipose stem cells on lymphangiogenesis in a murine tail lymphedema model. AB - BACKGROUND: Lymphedema is an underdiagnosed pathology which in industrialized countries mainly affects cancer patients that underwent lymph node dissection and/or radiation. Currently no effective therapy is available so that patients' life quality is compromised by swellings of the concerned body region. This unfortunate condition is associated with body imbalance and subsequent osteochondral deformations and impaired function as well as with an increased risk of potentially life threatening soft tissue infections. METHODS: The effects of PRP and ASC on angiogenesis (anti-CD31 staining), microcirculation (Laser Doppler Imaging), lymphangiogenesis (anti-LYVE1 staining), microvascular architecture (corrosion casting) and wound healing (digital planimetry) are studied in a murine tail lymphedema model. RESULTS: Wounds treated by PRP and ASC healed faster and showed a significantly increased epithelialization mainly from the proximal wound margin. The application of PRP induced a significantly increased lymphangiogenesis while the application of ASC did not induce any significant change in this regard. CONCLUSIONS: PRP and ASC affect lymphangiogenesis and lymphedema development and might represent a promising approach to improve regeneration of lymphatic vessels, restore disrupted lymphatic circulation and treat or prevent lymphedema alone or in combination with currently available lymphedema therapies. PMID- 26365475 TI - Orthopaedic firearm injuries in children and adolescents: An eight-year experience at a major urban trauma center. AB - INTRODUCTION: The purpose of this study is to describe the epidemiology of orthopaedic injuries incurred secondary to firearms among children and adolescents at a major metropolitan trauma center and to identify risk factors for complications and long-term morbidity. METHODS: A retrospective review was performed of consecutive patients 17 years of age and younger who sustained a firearm injury and required orthopaedic treatment at a major trauma center from 2006 to 2013. Patient demographics, injury mechanism, fracture classification, neurovascular injury, antibiotic administration, and length of hospitalization were recorded. Radiographic studies were used to determine fracture pattern, methods of stabilization, and time to union. Primary clinical outcomes include fracture nonunion, infection, and physeal arrest. RESULTS: 46 patients with a mean age of 12.7 years were treated for firearm related orthopaedic injuries. 72% of the patients were ages 13-17, while 28% were 12 years of age and younger. There were 28 violent injuries (21 assaults, 7 innocent bystanders) and 16 non violent injuries (15 unintentional discharges and 1 self-inflicted). There was a bimodal distribution of violent versus nonviolent mechanisms, with the majority of children 12 years of age and under sustaining non-violent injuries and adolescents more commonly injured with a violent mechanism. There were 44 fractures and 6 traumatic arthrotomies, with eight associated neurovascular injuries. Twenty-five patients had an orthopaedic procedure, with a total of 43 surgeries. Mean hospital length of stay was 6.8 days. There were five deep infections. Four patients developed non-unions and all of these patients had deep infections. The timing and duration of antibiotic therapy was not significantly different between those who did and did not develop infection. Of the non operatively treated fractures, there were no infections or non-unions at long term follow-up. CONCLUSIONS: Morbidity and mortality related to firearms is a growing public health problem in the United States. Results of this study suggest that gunshot related fractures had higher than anticipated morbidity, including permanent neurologic deficits, infection (11%) and fracture non-union (9%). More than half of patients underwent surgery and experienced long hospital stays secondary to the complexity of the injury. This epidemiological data on firearm injuries in children and adolescents is an impetus for prospective study, with the goal to increase awareness and develop treatment strategies for firearm related fractures. PMID- 26365476 TI - Late endocrine effects of cancer and cancer therapies in survivors of childhood malignancies. AB - The development of several cancer treatment modalities including surgery, radiotherapy and chemotherapy has improved the survival rates of childhood cancers over recent decades, leading to an increase in the population of childhood cancer survivors. Detailed epidemiological studies have demonstrated that childhood cancer survivors frequently develop medical complications months or years after cancer treatment. Endocrine complications are common in survivors, particularly those exposed to radiotherapy, total body irradiation and alkylating agents, and may involve dysfunction of the hypothalamic-pituitary axes, gonads, thyroid gland, bone and body composition as well as metabolic abnormalities. Early identification and proper management of these disorders can significantly improve the quality of life and reduce the morbidity and potentially mortality in this population. Multidisciplinary teams, expert physicians and the development of healthcare structures are key elements for improving the screening, surveillance, cost effectiveness and overall management of endocrine late effects of cancer therapies in childhood cancer survivors. The aim of the present review was to discuss the most important and common late endocrine effects of childhood cancer treatment. PMID- 26365477 TI - Bariatric surgery versus medications in the treatment of type 2 diabetes. AB - Type 2 diabetes mellitus (T2DM) is associated with increased risk of severe comorbidities and mortality; its prevalence is increasing worldwide, linked with the increasing prevalence of obesity. Weight loss prevents the development of T2DM in obese subjects, and can reverse T2DM in morbid obesity. This paper reviews bariatric surgery as a means for prevention and treatment of T2DM and its complications, in comparison with medical treatment, and analyzes the possible mechanisms involved. In morbidly obese patients bariatric surgery results in stable weight loss and long-term reduction in incidence and prevalence of obesity related comorbidities, especially T2DM. The efficacy of bariatric surgery in improving and normalizing glucose levels has been confirmed by a large number of studies, comparing surgery with medical therapy. When compared to each other, malabsorptive and mixed malabsorptive/restrictive surgery techniques have shown better outcomes than restrictive techniques in terms of T2DM remission. However it is demonstrated that T2DM can reappear in the following years, especially in patients with advanced age, female sex, longer duration of T2DM, poorer glycemic control, use of insulin before surgery and weight regain. Bariatric surgery is superior to conventional medical therapy in inducing significant weight loss and control of T2DM. Weight loss has pleiotropic effects: T2DM can disappear and then re-appear as a result of persistent beta-cells impairment, while other effects last much longer, as reduction of blood pressure and improvement of lipids and of kidney function. This is probably the reason for long-term prevention of cardiovascular events and of mortality in obese and in obese-diabetic patients. The effect of bariatric surgery on diabetic retinopathy is still controversial. PMID- 26365478 TI - Transradial versus transfemoral approach for percutaneous coronary intervention in cardiogenic shock: A radial-first centre experience and meta-analysis of published studies. AB - BACKGROUND: The transradial approach for percutaneous coronary intervention (PCI) is associated with a better outcome in myocardial infarction (MI), but patients with cardiogenic shock (CS) were excluded from most trials. AIMS: To compare outcomes of PCI for MI-related CS via the transradial versus transfemoral approach. METHODS: A prospective cohort of 101 consecutive patients admitted for PCI for MI-related CS were treated via the transradial (n=74) or transfemoral (n=27) approach. Cox proportional hazards models adjusted for prespecified variables and a propensity score for approach were used to compare mortality, death/MI/stroke and bleeding between the two groups. A complementary meta analysis of six studies was also performed. RESULTS: Patients in the transradial group were younger (P=0.039), more often male (P=0.002) and had lower GRACE and CRUSADE scores (P=0.003 and 0.001, respectively) and rates of cardiac arrest before PCI (P=0.009) and mechanical ventilation (P=0.006). Rates of PCI success were similar. At a mean follow-up of 756 days, death occurred in 40 (54.1%) patients in the transradial group versus 22 (81.5%) in the transfemoral group (adjusted hazard ratio [HR]: 0.49, 95% confidence interval [CI] 0.28-0.84; P=0.012). The transradial approach was associated with reduced rates of death/MI/stroke (adjusted HR: 0.53, 95%CI: 0.31-0.91; P=0.02) and major bleeding (adjusted HR: 0.34, 95%CI: 0.13-0.87; P=0.02). The meta-analysis confirmed the benefit of transradial access in terms of mortality (relative risk [RR]: 0.63, 95%CI: 0.58-0.68) and major bleeding (RR: 0.43, 95%CI: 0.32-0.59). CONCLUSION: The transradial approach in the setting of PCI for ischaemic CS is associated with a dramatic reduction in mortality, ischaemic and bleeding events, and should be preferred to the transfemoral approach in radial expert centres. PMID- 26365479 TI - The medical history of adults with complex congenital heart disease affects their social development and professional activity. AB - BACKGROUND: In recent decades, advances in surgery and therapeutic catheterization have steadily increased the life expectancy and prevalence of adults with congenital heart disease (CHD). AIMS: We assessed medical and psychosocial variables of adults with CHD, according to the disease complexity. METHODS: We included, from a single-centre observational cohort study, 135 consecutive adults with CHD (median age of 40 years, interquartile range: 28.0 51.0) followed in our cardiology unit, who answered a questionnaire assessing daily activity and psychosocial functioning. Disease complexity was classified according to the Bethesda conference. RESULTS: Cardiac malformation complexity was simple in 61 (45.2%), moderate in 50 (37.0%) and complex in 24 (17.8%) patients. Cardiac surgery had been performed in 86.5% of moderate and complex patients. Complications (such as heart failure, arrhythmia and pulmonary hypertension) were mainly observed in the complex group (P=0.003). Physical activity was lower in the complex group (no activity in 58.8%, but sport previously contraindicated in 50% of these; P=0.03). Education level tended to be lower in the complex and moderate groups than in the simple group (respectively, 31.2% and 33.3% vs. 45.7% had passed the Baccalaureate; P=0.47). The pass rate was lower in patients with complications (P=0.037) or more than one cardiac surgery (P=0.03). In the complex group, 56.3% of patients were unemployed (P=0.048). CONCLUSIONS: Complexity of heart disease and medical history affect education level and employment of adults with CHD. Academic education of children with a complex defect and career counselling are important to prevent unemployment among adults with CHD. PMID- 26365480 TI - The H6D genetic variation of GDF15 is associated with genesis, progress and prognosis in colorectal cancer. AB - BACKGROUND: Growth differentiation factor 15 (GDF15) plays important roles in the carcinogenesis of many types of tumors. The aim of this study was to investigate whether H6D polymorphism is contributed to the genesis, progress and prognosis of colorectal cancer (CRC) in Chinese population. METHODS: Pyrosequencing was used to determine the H6D genotypes. The relationship between the genotypes and clinical characteristics was analyzed. RESULTS: The frequency of CG+GG genotype in the GDF15 H6D polymorphism was significantly increased in CRC patients when compared with controls [odds ratio (OR), 1.543; 95% confidence interval (95% CI), 1.138-2.094, P=0.005]. We also found that the patients with CG+GG genotype had an increased risk of death from colon cancer than those carrying homozygote CC [hazard ratio (HR), 2.472; 95% CI, 1.172-5.214; P=0.017] and the patients with CG+GG genotype of colon cancer also have a positive correlation with distant metastasis than those carrying homozygote CC (chi(2)=4.087, P=0.043). For the first time, H6D was also identified as somatic mutation when compared the H6D genotype in tumor tissues and their matched normal tissues, and the mutation rate is 7.2%. The male CRC patients with the H6D mutation were susceptible to distant metastasis (P=0.028, chi(2)=4.820) and had a relatively poor prognosis. CONCLUSION: Our results suggest that the H6D genetic variant may be considered as a biomarker of tumorgenesis, metastasis and prognosis in colorectal cancer in Chinese population. PMID- 26365481 TI - [Comparison of the findings of rectal examination and ultrasonographic findings in horses with colic]. AB - OBJECTIVE: The examination of patients suffering from an acute abdomen routinely comprises both clinical and rectal examinations, and is ever more frequently accompanied by an ultrasonographic abdominal examination. The aim of the study was to compare the findings as defined through rectal examination with the results of the ultrasonographic examination for different forms of colic. MATERIAL AND METHODS: In a retrospective study, the patient records of the Large Animal Clinic of the University of Leipzig from 2012 and 2013 were analysed, and those of horses suffering from colic were included. Diagnoses made through rectal and ultrasonographic examination were grouped and compared with the diagnoses made during colic surgery or pathologic examination, which served as the gold standard. Horses that underwent conservative treatment had a definitive diagnosis assigned only in cases where a pathognostic rectal finding defined the diagnosis. Based on these data, sensitivity, specificity and positive and negative predictive values were calculated for both techniques. RESULTS: Ultrasonography was more sensitive than rectal examination in cases of small intestinal occlusion (97.1% vs. 50.7%), torsion of the large colon in the long axis (63.2% vs. 26.3%) and dislocation of the large colon into the nephrosplenic space (90.9% vs. 72.7%). Rectal examination was more sensitive than ultrasonographic examination in cases of other types of dislocation of the large colon (96.5% vs. 8.8%) and of constipations of the large colon (93.6% vs. 29.8%). CONCLUSION AND CLINICAL RELEVANCE: In cases of severe diseases, including small intestinal occlusions and torsions of the large colon, ultrasonography helps to better identify and more precisely diagnose conditions that in most cases require abdominal surgery than rectal examination. Therefore, under hospital conditions, it is highly advisable to include ultrasonography in the routine examination of the equine acute abdomen. However, this technique does not replace the traditional rectal examination, which is superior in the diagnosis of dislocations and constipations of the large colon as well as diseases of the caecum. PMID- 26365482 TI - Electrocardiograph abnormalities in intracerebral hemorrhage. AB - This study investigated the prevalence and type of electrocardiography (ECG) abnormalities, and their possible association with the clinical/radiological findings in 118 consecutive patients with non-traumatic, non-neoplastic intracerebral hemorrhage (ICH). ECG frequently demonstrates abnormalities in patients with ischemic stroke and subarachnoid hemorrhage, but little is known of ECG changes in ICH patients. Clinical and radiological information was retrospectively reviewed. ECG recordings that were obtained within 24 hours of the initial hemorrhage were analyzed. Sixty-six patients (56%) had one or more ECG abnormalities. The most frequent was ST depression (24%), followed by left ventricular hypertrophy (20%), corrected QT interval (QTc) prolongation (19%), and T wave inversion (19%). The logistic regression analysis demonstrated the following: insular involvement was an independent predictive factor of ST depression (p<0.001; odds ratio OR 10.18; 95% confidence interval [CI] 2.84 36.57); insular involvement (p<0.001; OR 23.98; 95% CI 4.91-117.11) and presence of intraventricular hemorrhage (p<0.001; OR 8.72; 95% CI 2.69-28.29) were independent predictive factors of QTc prolongation; deep hematoma location (p<0.001; OR 19.12; 95% CI 3.82-95.81) and hematoma volume >30 ml (p=0.001; OR 6.58; 95% CI 2.11-20.46) were independent predictive factors of T wave inversion. We demonstrate associations between ECG abnormalities and detailed characteristics of ICH. PMID- 26365483 TI - Characteristics of pulmonary Mycobacterium avium complex disease diagnosed later in follow-up after negative mycobacterial study including bronchoscopy. AB - BACKGROUND: We occasionally experience cases suspected of pulmonary Mycobacterium avium complex (MAC) disease without positive bacterial cultures. OBJECTIVE: To evaluate features of pulmonary MAC cases diagnosed later in the follow-up after negative intensive investigation. METHODS: We defined and compared three groups; the first study negative (FSN) group, the first study positive (FSP) group, and MAC negative group. The FSN group consisted of patients negative for MAC isolation by bronchial washing performed between 2007 and 2011, but positive later. Patients with positive MAC cultures in the first study were incorporated into the FSP group. MAC negative group consisted of MAC suspects without MAC isolation in the follow-up. RESULTS: Twenty-four patients were classified as FSN group, 61 as MAC negative group and 265 as FSP group. FSN group exhibited more solitary nodule pattern (n = 7 in FSN, n = 6 in FSP; p < 0.001) and less nodular/bronchiectatic (NB) diseases (n = 17 in FSN, n = 245 in FSP; p < 0.001). When limited to NB type, the FSP group had more cavitations (6% in FSN, 32% in FSP; p = 0.028). Patients with more than three lung lobes involved were more frequent in the FSN group compared with FSP group with negative sputum cultures (65% vs 34%; p = 0.014) and with MAC negative group (65% vs 28%; p = 0.009). CONCLUSIONS: Patients diagnosed as pulmonary MAC disease in the follow-up duration tend to show solitary nodular pattern or NB pattern without cavitation. In FSN patients with NB pattern, more lung lobes were involved in the first study, suggesting subsequent MAC infection onto the underlying ectatic bronchi. PMID- 26365484 TI - One-leg hop kinematics 20 years following anterior cruciate ligament rupture: Data revisited using functional data analysis. AB - BACKGROUND: Despite interventions, anterior cruciate ligament ruptures can cause long-term deficits. To assist in identifying and treating deficiencies, 3D-motion analysis is used for objectivizing data. Conventional statistics are commonly employed to analyze kinematics, reducing continuous data series to discrete variables. Conversely, functional data analysis considers the entire data series. METHODS: Here, we employ functional data analysis to examine and compare the entire time-domain of knee-kinematic curves from one-leg hops between and within three groups. All subjects (n=95) were part of a long-term follow-up study involving anterior cruciate ligament ruptures treated ~20 years ago conservatively with physiotherapy only or with reconstructive surgery and physiotherapy, and matched knee-healthy controls. FINDINGS: Between-group differences (injured leg, treated groups; non-dominant leg, controls) were identified during the take-off and landing phases, and in the sagittal (flexion/extension) rather than coronal (abduction/adduction) and transverse (internal/external) planes. Overall, surgical and control groups demonstrated comparable knee-kinematic curves. However, compared to controls, the physiotherapy-only group exhibited less flexion during the take-off (0-55% of the normalized phase) and landing (44-73%) phase. Between-leg differences were absent in controls and the surgically treated group, but observed during the flight (4 22%, injured leg>flexion) and the landing (57-85%, injured leg= 25 kg/m(2)) who were newly started on dofetilide based on ABW. Patients were categorized into (i) the different-dose group if their CrCl calculated based on the ideal body weight (IBW) resulted in a lower initial dofetilide dose compared with ABW-based CrCl and (ii) the same-dose group if they would have the same initial dose based on IBW and ABW. The primary outcome was dofetilide dose reduction or discontinuation due to prolongation of the corrected QT interval during the first 3 days of dofetilide therapy. Multivariable logistic regression analysis was performed to identify factors predicting the risk of primary outcome. RESULTS AND DISCUSSION: Of the 132 patients included in the study, 29 (22.0%) were in the different-dose group and 40 (30.3%) had the primary outcome. The per cent of patients with the primary outcome was not statistically significantly different between the different-dose and same-dose groups (37.9% vs. 28.2%; P = 0.31). Diabetes mellitus was a significant predictor for the primary outcome (odds ratio 2.54; 95% confidence interval 1.05-6.15). WHAT IS NEW AND CONCLUSION: Our study provides the evidence on the safety of the current dofetilide dosing recommendation in overweight and obese populations in clinical practice. Current ABW-based dofetilide dosing is reasonable in overweight and obese patients. PMID- 26365490 TI - Systematic identification of factors for provirus silencing in embryonic stem cells. AB - Embryonic stem cells (ESCs) repress the expression of exogenous proviruses and endogenous retroviruses (ERVs). Here, we systematically dissected the cellular factors involved in provirus repression in embryonic carcinomas (ECs) and ESCs by a genome-wide siRNA screen. Histone chaperones (Chaf1a/b), sumoylation factors (Sumo2/Ube2i/Sae1/Uba2/Senp6), and chromatin modifiers (Trim28/Eset/Atf7ip) are key determinants that establish provirus silencing. RNA-seq analysis uncovered the roles of Chaf1a/b and sumoylation modifiers in the repression of ERVs. ChIP seq analysis demonstrates direct recruitment of Chaf1a and Sumo2 to ERVs. Chaf1a reinforces transcriptional repression via its interaction with members of the NuRD complex (Kdm1a, Hdac1/2) and Eset, while Sumo2 orchestrates the provirus repressive function of the canonical Zfp809/Trim28/Eset machinery by sumoylation of Trim28. Our study reports a genome-wide atlas of functional nodes that mediate proviral silencing in ESCs and illuminates the comprehensive, interconnected, and multi-layered genetic and epigenetic mechanisms by which ESCs repress retroviruses within the genome. PMID- 26365491 TI - Enhancer divergence and cis-regulatory evolution in the human and chimp neural crest. AB - cis-regulatory changes play a central role in morphological divergence, yet the regulatory principles underlying emergence of human traits remain poorly understood. Here, we use epigenomic profiling from human and chimpanzee cranial neural crest cells to systematically and quantitatively annotate divergence of craniofacial cis-regulatory landscapes. Epigenomic divergence is often attributable to genetic variation within TF motifs at orthologous enhancers, with a novel motif being most predictive of activity biases. We explore properties of this cis-regulatory change, revealing the role of particular retroelements, uncovering broad clusters of species-biased enhancers near genes associated with human facial variation, and demonstrating that cis-regulatory divergence is linked to quantitative expression differences of crucial neural crest regulators. Our work provides a wealth of candidates for future evolutionary studies and demonstrates the value of "cellular anthropology," a strategy of using in-vitro derived embryonic cell types to elucidate both fundamental and evolving mechanisms underlying morphological variation in higher primates. PMID- 26365493 TI - A New Application for Albumin Dialysis in Extracorporeal Organ Support: Characterization of a Putative Interaction Between Human Albumin and Proinflammatory Cytokines IL-6 and TNFalpha. AB - Albumin dialysis in extracorporeal organ support is often performed in the treatment of liver failure as it facilitates the removal of toxic components from the blood. Here, we describe a possible effect of albumin dialysis on proinflammatory cytokine levels in vitro. Initially, albumin samples were incubated with different amounts of cytokines and analyzed by enzyme-linked immunosorbent assay (ELISA). Analysis of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNFalpha) levels indicated that increased concentrations of albumin reduce the measureable amount of the respective cytokines. This led to the hypothesis that the used proinflammatory cytokines may interact with albumin. Size exclusion chromatography of albumin spiked with cytokines was carried out using high-performance liquid chromatography analysis. The corresponding fractions were evaluated by immunoblotting. We detected albumin and cytokines in the same fractions indicating an interaction of the small-sized cytokines IL-6 and TNFalpha with the larger-sized albumin. Finally, a two-compartment albumin dialysis in vitro model was used to analyze the effect of albumin on proinflammatory cytokines in the recirculation circuit during 6-h treatment. These in vitro albumin dialysis experiments indicated a significant decrease of IL-6, but not of TNFalpha, when albumin was added to the dialysate solution. Taken together, we were able to show a putative in vitro interaction of human albumin with the proinflammatory cytokine IL-6, but with less evidence for TNFalpha, and demonstrated an additional application for albumin dialysis in liver support therapy where IL-6 removal might be indicated. PMID- 26365494 TI - Relationship of CTLA4 and CD28 polymorphisms with lung involvement, HRCT findings and pulmonary function tests in Turkish patients with ankylosing spondylitis. AB - BACKGROUND AND AIMS: Ankylosing spondylitis (AS) is a multisystem disorder with ocular, pulmonary, and cardiovascular involvement. The incidence of pulmonary involvement varies from 1 to 52%. Abnormal T-cell function-derived immune responses are involved in AS pathogenesis. Numerous genes such as CTLA4 and CD28 control T-cell functions. In this study, we aimed to address the relationship between CTLA4 and CD28 polymorphisms and lung involvement in Turkish patients with AS. METHODS: A cross-sectional evaluation of 80 healthy and 89 AS subjects with no active infection or malignancy was performed to determine the relationship between pulmonary involvement and CTLA4 and CD28 gene polymorphisms. All patients were assessed for clinical, radiological, and spirometric findings. Descriptive statistics, chi-square tests, and independent-sample t-tests were used for statistical analyses. RESULTS: All patients with the CD28 CC genotype (n = 4) had abnormal HRCT, but it was not significant (p = 0.47). All of the normal HRCT patients have CD 28 T alleles. In addition to this data ; 4 patients who have not any T alleles have abnormal HRCT finding. It was significant and was considered that T genotype have protective effect (p= 0,047) on radiologic involvement but no other association was found between CTLA4 and CD28 gene polymorphism with respect to pulmonary function tests (PFT), diffusion capacity, and clinical characteristics in the Turkish patients with AS. CONCLUSION: Our results suggest a possible association of CTLA4 and CD28 variants with AS pulmonary involvement. Furthermore, these results may lead to the development of new therapeutic agents to control more aggressive forms of the disease. However, further studies are needed in larger populations. PMID- 26365495 TI - Hierarchical FeTiO3-TiO2 hollow spheres for efficient simulated sunlight-driven water oxidation. AB - Oxygen generation is the key step for the photocatalytic overall water splitting and considered to be kinetically more challenging than hydrogen generation. Here, an effective water oxidation catalyst of hierarchical FeTiO3-TiO2 hollow spheres are prepared via a two-step sequential solvothermal processes and followed by thermal treatment. The existence of an effective heterointerface and built-in electric field in the surface space charge region in FeTiO3-TiO2 hollow spheres plays a positive role in promoting the separation of photoinduced electron-hole pairs. Surface photovoltage, transient-state photovoltage, fluorescence and electrochemical characterization are used to investigate the transfer process of photoinduced charge carriers. The photogenerated charge carriers in the hierarchical FeTiO3-TiO2 hollow spheres with a proper molar ratio display much higher separation efficiency and longer lifetime than those in the FeTiO3 alone. Moreover, it is suggested that the hierarchical porous hollow structure can contribute to the enhancement of light utilization, surface active sites and material transportation through the framework walls. This specific synergy significantly contributes to the remarkable improvement of the photocatalytic water oxidation activity of the hierarchical FeTiO3-TiO2 hollow spheres under simulated sunlight (AM1.5). PMID- 26365496 TI - The long tail and rare disease research: the impact of next-generation sequencing for rare Mendelian disorders. AB - There are an estimated 6000-8000 rare Mendelian diseases that collectively affect 30 million individuals in the United States. The low incidence and prevalence of these diseases present significant challenges to improving diagnostics and treatments. Next-generation sequencing (NGS) technologies have revolutionized research of rare diseases. This article will first comment on the effectiveness of NGS through the lens of long-tailed economics. We then provide an overview of recent developments and challenges of NGS-based research on rare diseases. As the quality of NGS studies improve and the cost of sequencing decreases, NGS will continue to make a significant impact on the study of rare diseases moving forward. PMID- 26365497 TI - A novel gap-PCR with high resolution melting analysis for the detection of alpha thalassaemia Southeast Asian and Filipino beta degrees -thalassaemia deletion. AB - Homozygosity for the alpha-thalassaemia Southeast Asian (alpha-SEA) and Filipino beta degrees -thalassaemia (beta-FIL) deletions can cause serious complications leading to foetal death or life-long blood transfusions. A rapid and accurate molecular detection assay is essential in populations where the deletions are common. In this study, gap-polymerase chain reaction (PCR) with high resolution melting (HRM) analysis was developed to detect both the large deletions. Melting curves at 86.9 +/- 0.1 degrees C were generated by normal individuals without the alpha-SEA deletion, 84.7 +/- 0.1 degrees C by homozygous alpha-SEA deletion individuals and two melting curves at 84.7 +/- 0.1 degrees C and 86.9 +/- 0.1 degrees C by alpha-SEA deletion carriers. Normal individuals without the beta-FIL deletion produce amplicons with a melting temperature (Tm) at 74.6 +/- 0.1 degrees C, homozygous beta-FIL individuals produce amplicons with Tm at 73.6 +/- 0.1 degrees C and heterozygous beta-FIL individuals generate two amplicons with Tm at 73.6 +/- 0.1 degrees C and 74.6 +/- 0.1 degrees C. Evaluation using blinded tests on 220 DNA samples showed 100% sensitivity and specificity. The developed assays are sensitive and specific for rapid molecular and prenatal diagnosis for the alpha-SEA and beta-FIL deletions. PMID- 26365498 TI - Missing CD4+ cell response in randomized clinical trials of maraviroc and dolutegravir. AB - BACKGROUND: Missing data can compromise inferences from clinical trials, yet the topic has received little attention in the clinical trial community. Shortcomings in commonly used methods used to analyze studies with missing data (complete case, last- or baseline-observation carried forward) have been highlighted in a recent Food and Drug Administration-sponsored report. This report recommends how to mitigate the issues associated with missing data. We present an example of the proposed concepts using data from recent clinical trials. METHODS: CD4+ cell count data from the previously reported SINGLE and MOTIVATE studies of dolutegravir and maraviroc were analyzed using a variety of statistical methods to explore the impact of missing data. Four methodologies were used: complete case analysis, simple imputation, mixed models for repeated measures, and multiple imputation. We compared the sensitivity of conclusions to the volume of missing data and to the assumptions underpinning each method. RESULTS: Rates of missing data were greater in the MOTIVATE studies (35%-68% premature withdrawal) than in SINGLE (12%-20%). The sensitivity of results to assumptions about missing data was related to volume of missing data. Estimates of treatment differences by various analysis methods ranged across a 61 cells/mm3 window in MOTIVATE and a 22 cells/mm3 window in SINGLE. CONCLUSIONS: Where missing data are anticipated, analyses require robust statistical and clinical debate of the necessary but unverifiable underlying statistical assumptions. Multiple imputation makes these assumptions transparent, can accommodate a broad range of scenarios, and is a natural analysis for clinical trials in HIV with missing data. PMID- 26365499 TI - Nucleic acid vaccination strategies against infectious diseases. AB - INTRODUCTION: Gene vaccines are an interesting and emerging alternative for the prevention of infectious diseases, as well as in the treatment of other pathologies including cancer, allergies, autoimmune diseases, or even drug dependencies. When applied to the target organism, these vaccines induce the expression of encoded antigens and elicit the corresponding immune response, with the potential ability of being able to induce antibody-, helper T cell-, and cytotoxic T cell-mediated immune responses. AREAS COVERED: Special attention is paid to the variety of adjuvants that may be co-administered to enhance and/or to modulate immune responses, and to the methods of delivery. Finally, this article reviews the efficacy data of gene vaccines against infectious diseases released from current clinical trials. EXPERT OPINION: Taken together, this approach will have a major impact on future strategies for the prevention of infectious diseases. Better-designed nucleic acid constructs, novel delivery technologies, as well as the clarification of the mechanisms for antigen presentation will improve the potential applications of this vaccination strategy against microbial pathogens. PMID- 26365500 TI - Ecological risk assessments and context-dependence analysis of heavy metal contamination in the sediments of mangrove swamp in Leizhou Peninsula, China. AB - Sediments in eight types of mangroves were sampled in the Leizhou Peninsula. Heavy metals were analyzed to investigate the effects on metal distribution of mangrove communities, to evaluate contamination levels, identify sources and relationships between the two. Results showed that mangrove communities have effects on most heavy metal distributions in sediments, especially in the sediment with shrub communities of Aegiceras corniculatum where the contents of many metals are highest. As, Cr and Ni were identified as metal pollutants of primary concern, while Cd was of no concern. Zn, Pb, As mainly originated from anthropogenic source while the other metals are geogenic. Heavy metal distributions were affected by the independent and joint effects of landscape and sediment context; landscape context explains more variations in heavy metals than does sediment physicochemical variables. Total sulfur, total phosphorus and total potassium in sediment, and the existence of paddy field and forest land within 2000m around the sampling sites are significant variables also. PMID- 26365501 TI - Trace metal variability in coastal waters of San Jorge Bay, Antofagasta, Chile: An environmental evaluation and statistical approach to propose local background levels. AB - Between 2008 and 2011, twelve metals from 384 coastal waters samples from San Jorge Bay (Antofagasta, northern Chile) were collected and analyzed. The goal was to evaluate the quality of the bay's water bodies according to the current Chilean Quality Guideline and to establish background levels for these metals. The result suggests that the coastal waters of San Jorge Bay are of very good quality suitable for recreational activities involving human body contact. The natural background thresholds established for this bay were significantly lower than primary and secondary water quality guidelines. The distribution of Cu, Zn and Pb, along the bay's coastline provides evidence of the effects of industrial activity. Both situations suggest that the threshold indicated in the environmental guidelines of the Chilean legislation may be overestimated and do not represent pollution-free environments. PMID- 26365502 TI - Two-dimensional topological insulators with tunable band gaps: Single-layer HgTe and HgSe. AB - Two-dimensional (2D) topological insulators (TIs) with large band gaps are of great importance for the future applications of quantum spin Hall (QSH) effect. Employing ab initio electronic calculations we propose a novel type of 2D topological insulators, the monolayer (ML) low-buckled (LB) mercury telluride (HgTe) and mercury selenide (HgSe), with tunable band gap. We demonstrate that LB HgTe (HgSe) monolayers undergo a trivial insulator to topological insulator transition under in-plane tensile strain of 2.6% (3.1%) due to the combination of the strain and the spin orbital coupling (SOC) effects. Furthermore, the band gaps can be tuned up to large values (0.2 eV for HgTe and 0.05 eV for HgSe) by tensile strain, which far exceed those of current experimentally realized 2D quantum spin Hall insulators. Our results suggest a new type of material suitable for practical applications of 2D TI at room-temperature. PMID- 26365503 TI - Radiofrequency ablation versus surgical resection for hepatocellular carcinoma within the Milan criteria: A study of 281 Western patients. AB - OBJECTIVES: The aim of this study was to compare survival between radiofrequency ablation (RFA) and surgical resection (SR) in patients with hepatocellular carcinoma (HCC) within Milan criteria. METHODS: From January 2004 to December 2013 we consecutively and retrospectively included all patients with first occurrence of HCC within Milan criteria receiving SR or RFA as first-line treatment. The cumulative overall survival (OS) and disease-free survival (DFS) were compared after inverse probability weighting (including confounding factor). RESULTS: A total of 281 patients (RFA 178, SR 103) were enrolled. In multivariate Cox regression RFA and SR were not independent predictors of survival or recurrence. The respective weighted 5 years OS and DFS for patients with propensity scores between 0.1-0.9 in the SR and RFA groups were 54-33% and 60 16.9%, P = 0.695 and P = 0.426, respectively. Local tumour progression rate did not differ according to treatment (P = 0.523). Major complication rate was higher in the SR group, P = 0.001. Hospitalisation duration was lower in the RFA group (mean 2.19 days, range 2-7) than in the SR group (mean 10.2 days, range 3-30), P < 0.001. CONCLUSION: This large Western study has shown that OS and DFS did not differ after RFA (using mainly multipolar devices) and SR, for HCC within the Milan criteria in a European population, with a shorter hospitalisation time and a lower complication rate for RFA. PMID- 26365504 TI - Callosal anatomical and effective connectivity between primary motor cortices predicts visually cued bimanual temporal coordination performance. AB - Default in-phase coupling of hand movements needs to be suppressed when temporal coordination is required for out-of-phase bimanual movements. There is lack of knowledge on how the brain overrides these default in-phase movements to enable a required interval of activity between hands. We used a visually cued bimanual temporal coordination (vc-BTC) paradigm with a constant rhythmical time base of 1 s, to test the accuracy of in-phase and out-of-phase (0.1, 0.2,...,0.9) finger tapping. We hypothesized that (1) stronger anatomical and effective interhemispheric connectivity between the hand areas of the primary motor cortex (M1HAND) predict higher temporal offsets between hands in the out-of-phase conditions of the vc-BTC; (2) patients with relapsing-remitting multiple sclerosis (RRMS) and clinically isolated syndrome (CIS) have reduced interhemispheric connectivity and altered between-hand coupling. Anatomical connectivity was determined by fractional anisotropy of callosal hand motor fibers (FA-hCMF). Effective connectivity was probed by short interval interhemispheric inhibition (S-IHI) using paired-coil transcranial magnetic stimulation (TMS). In healthy subjects, higher FA-hCMF and S-IHI correlated with higher temporal offsets between hands in the out-of-phase conditions of the tapping test. FA-hCMF was reduced in patients with RRMS but not in CIS, while S IHI was reduced in both patient groups. These abnormalities were associated with smaller temporal offsets between hands leading to less deviation from the required phasing in the out-of-phase tapping conditions. Findings provide multiple levels of evidence that callosal anatomical and effective connectivity between the hand areas of the motor cortices play important roles in visually cued bimanual temporal coordination performance. PMID- 26365506 TI - Common and distinct networks for self-referential and social stimulus processing in the human brain. AB - Self-referential processing is a complex cognitive function, involving a set of implicit and explicit processes, complicating investigation of its distinct neural signature. The present study explores the functional overlap and dissociability of self-referential and social stimulus processing. We combined an established paradigm for explicit self-referential processing with an implicit social stimulus processing paradigm in one fMRI experiment to determine the neural effects of self-relatedness and social processing within one study. Overlapping activations were found in the orbitofrontal cortex and in the intermediate part of the precuneus. Stimuli judged as self-referential specifically activated the posterior cingulate cortex, the ventral medial prefrontal cortex, extending into anterior cingulate cortex and orbitofrontal cortex, the dorsal medial prefrontal cortex, the ventral and dorsal lateral prefrontal cortex, the left inferior temporal gyrus, and occipital cortex. Social processing specifically involved the posterior precuneus and bilateral temporo parietal junction. Taken together, our data show, not only, first, common networks for both processes in the medial prefrontal and the medial parietal cortex, but also, second, functional differentiations for self-referential processing versus social processing: an anterior-posterior gradient for social processing and self-referential processing within the medial parietal cortex and specific activations for self-referential processing in the medial and lateral prefrontal cortex and for social processing in the temporo-parietal junction. PMID- 26365505 TI - Structure and function of the amygdaloid NPY system: NPY Y2 receptors regulate excitatory and inhibitory synaptic transmission in the centromedial amygdala. AB - The amygdala is essential for generating emotional-affective behaviors. It consists of several nuclei with highly selective, elaborate functions. In particular, the central extended amygdala, consisting of the central amygdala (CEA) and the bed nucleus of the stria terminalis (BNST) is an essential component actively controlling efferent connections to downstream effectors like hypothalamus and brain stem. Both, CEA and BNST contain high amounts of different neuropeptides that significantly contribute to synaptic transmission. Among these, neuropeptide Y (NPY) has emerged as an important anxiolytic and fear reducing neuromodulator. Here, we characterized the expression, connectivity and electrophysiological function of NPY and Y2 receptors within the CEA. We identified several NPY-expressing neuronal populations, including somatostatin- and calretinin-expressing neurons. Furthermore, in the main intercalated nucleus, NPY is expressed primarily in dopamine D1 receptor-expressing neurons but also in interspersed somatostatin-expressing neurons. Interestingly, NPY neurons did not co-localize with the Y2 receptor. Retrograde tract tracing experiments revealed that NPY neurons reciprocally connect the CEA and BNST. Functionally, the Y2 receptor agonist PYY3-36, reduced both, inhibitory as well as excitatory synaptic transmission in the centromedial amygdala (CEm). However, we also provide evidence that lack of NPY or Y2 receptors results in increased GABA release specifically at inhibitory synapses in the CEm. Taken together, our findings suggest that NPY expressed by distinct populations of neurons can modulate afferent and efferent projections of the CEA via presynaptic Y2 receptors located at inhibitory and excitatory synapses. PMID- 26365507 TI - Strategies used by nurses, academics and students to overcome intercultural communication challenges. AB - Nurse clinicians and academics need to understand intercultural communication challenges to improve their communication skills and better support students' learning. Gaps exist in the literature regarding intercultural communication resources for students, academics and clinicians. The aim of this study was to explore the experiences of clinical nurses, nurse academics, and student nurses regarding intercultural communication challenges. Data were collected using focus group interviews with nineteen clinical facilitators (nurses who supervise nursing students in clinical practice), five clinical nurses, and ten nursing students. Seven nurse academics were interviewed via telephone. The purposive sample was drawn from a tertiary hospital and a university in Australia. Participants were invited to discuss challenging intercultural scenarios they had experienced including strategies they used to overcome such challenges. Using qualitative content analysis data were analysed resulting in four categories which were: 1) prejudice based on cultural diversity; 2) unfamiliarity with cultural boundaries; 3) stereotyping cultural behaviours; and 4) difficulty understanding English. Strategies participants used to mitigate challenges included resorting to cultural validation through alliance building, proactively seeking clarification, and acquiring cultural awareness knowledge. This study highlights intercultural challenges students, clinicians and academics face and signpost the way forward with useful strategies to better inform nurse education. PMID- 26365508 TI - Beyond water homeostasis: Diverse functional roles of mammalian aquaporins. AB - BACKGROUND: Aquaporin (AQP) water channels are best known as passive transporters of water that are vital for water homeostasis. SCOPE OF REVIEW: AQP knockout studies in whole animals and cultured cells, along with naturally occurring human mutations suggest that the transport of neutral solutes through AQPs has important physiological roles. Emerging biophysical evidence suggests that AQPs may also facilitate gas (CO2) and cation transport. AQPs may be involved in cell signalling for volume regulation and controlling the subcellular localization of other proteins by forming macromolecular complexes. This review examines the evidence for these diverse functions of AQPs as well their physiological relevance. MAJOR CONCLUSIONS: As well as being crucial for water homeostasis, AQPs are involved in physiologically important transport of molecules other than water, regulation of surface expression of other membrane proteins, cell adhesion, and signalling in cell volume regulation. GENERAL SIGNIFICANCE: Elucidating the full range of functional roles of AQPs beyond the passive conduction of water will improve our understanding of mammalian physiology in health and disease. The functional variety of AQPs makes them an exciting drug target and could provide routes to a range of novel therapies. PMID- 26365509 TI - Multidimensional significance of crystallin protein-protein interactions and their implications in various human diseases. AB - BACKGROUND: Crystallins are the important structural and functional proteins in the eye lens responsible for refractive index. Post-translational modifications (PTMs) and mutations are major causative factors that affect crystallin structural conformation and functional characteristics thus playing a vital role in the etiology of cataractogenesis. SCOPE OF REVIEW: The significance of crystallin protein-protein interactions (PPIs) in the lens and non-lenticular tissues is summarized. MAJOR CONCLUSIONS: Aberrancy of PPIs between crystallin, its associated protein and metal ions has been accomplished in various human diseases including cataract. A detailed account on multidimensional structural and functional significance of crystallin PPI in humans must be brought into limelight, in order to understand the biochemical and molecular basis augmenting the aberrancies of such interaction. In this scenario, the present review is focused to shed light on studies which will aid to expand our present understanding on disease pathogenesis related to loss of PPI thereby paving the way for putative future therapeutic targets to curb such diseases. GENERAL SIGNIFICANCE: The interactions with alpha-crystallins always aid to protect their structural and functional characteristics. The up-regulation of alphaB-crystallin in the non-lenticular tissues always decodes as biomarker for various stress related disorders. For better understanding and treatment of various diseases, PPI studies provide overall outline about the structural and functional characteristics of the proteins. This information not only helps to find out the route of cataractogenesis but also aid to identify potential molecules to inhibit/prevent the further development of such complicated phenomenon. This article is part of a Special Issue entitled Crystallin Biochemistry in Health and Disease. PMID- 26365510 TI - Which Extrinsic and Intrinsic Factors are Associated with Non-Contact Injuries in Adult Cricket Fast Bowlers? AB - BACKGROUND: The high prevalence of injury amongst cricket fast bowlers exposes a great need for research into the risk factors associated with injury. Both extrinsic (environment-related) and intrinsic (person-related) risk factors are likely to be implicated within the high prevalence of non-contact injury amongst fast bowlers in cricket. Identifying and defining the relative importance of these risk factors is necessary in order to optimize injury prevention efforts. OBJECTIVE: The objective of this review was to assess and summarize the scientific literature related to the extrinsic and intrinsic factors associated with non-contact injury inherent to adult cricket fast bowlers. METHOD: A systematic review was performed in compliance with the PRISMA guidelines. This review considered both experimental and epidemiological study designs. Studies that included male cricket fast bowlers aged 18 years or above, from all levels of play, evaluating the association between extrinsic/intrinsic factors and injury in fast bowlers were considered for inclusion. The three-step search strategy aimed at finding both published and unpublished studies from all languages. The searched databases included MEDLINE via PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Cochrane Controlled Trials Register in the Cochrane Library, Physiotherapy Evidence Database (PEDro), ProQuest 5000 International, ProQuest Health and Medical Complete, EBSCO MegaFile Premier, Science Direct, SPORTDiscus with Full Text and SCOPUS (prior to 28 April 2015). Initial keywords used were 'cricket', 'pace', 'fast', 'bowler', and 'injury'. Papers which fitted the inclusion criteria were assessed by two independent reviewers for methodological validity prior to inclusion in the review using standardized critical appraisal instruments from the Joanna Briggs Institute Meta Analysis of Statistics Assessment and Review Instrument (JBI MAStARI). RESULTS: A total of 16 studies were determined to be suitable for inclusion in this systematic review. The mean critical appraisal score of the papers included in this study was 6.88 (SD 1.15) out of a maximum of 9. The following factors were found to be associated with injury: bowling shoulder internal rotation strength deficit, compromised dynamic balance and lumbar proprioception (joint position sense), the appearance of lumbar posterior element bone stress, degeneration of the lumbar disc on magnetic resonance imaging (MRI), and previous injury. Conflicting results were found for the association of quadratus lumborum (QL) muscle asymmetry with injury. Technique-related factors associated with injury included shoulder-pelvis flexion-extension angle, shoulder counter-rotation, knee angle, and the proportion of side-flexion during bowling. Bowling workload was the only extrinsic factor associated with injury in adult cricket fast bowlers. A high bowling workload (particularly if it represented a sudden upgrade from a lower workload) increased the subsequent risk to sustaining an injury 1, 3 or 4 weeks later. CONCLUSION: Identifying the factors associated with injury is a crucial step which should precede the development of, and research into, the effectiveness of injury prevention programs. Once identified, risk factors may be included in pre-participation screening tools and injury prevention programs, and may also be incorporated in future research projects. Overall, the current review highlights the clear lack of research on factors associated with non-contact injury, specifically in adult cricket fast bowlers. SYSTEMATIC REVIEW REGISTRATION NUMBER: Johanna Briggs Institute Database of Systematic Reviews and Implementation Reports 1387 (Olivier et al., JBI Database Syst Rev Implement Rep 13(1):3-13. doi: 10.11124/jbisrir-2015-1387 , 2015). PMID- 26365511 TI - Reprogrammed Functional Brown Adipocytes Ameliorate Insulin Resistance and Dyslipidemia in Diet-Induced Obesity and Type 2 Diabetes. AB - Brown adipocytes (BAs) play important roles in body temperature regulation, energy balance, and carbohydrate and lipid metabolism. Activities of BAs are remarkably diminished in obese and diabetic patients, providing possibilities of transplanting functional BAs resulting in therapeutic benefit. Here, we show generation of functional BAs by cellular reprogramming procedures. Transduction of the PRDM16 gene into iPSC-derived embryoid bodies induced BA phenotypes (iBAs). Moreover, normal human fibroblasts were directly converted into BAs (dBAs) by C/EBP-beta and C-MYC gene transduction. Approximately 90% of the fibroblasts were successfully converted within 12 days. The dBAs were highly active in mitochondrial biogenesis and oxidative metabolism. Mouse dBAs were induced by Prdm16, C/ebp-beta, and L-myc genes, and after transplantation, they significantly reduced diet-induced obesity and insulin resistance in an UCP1 dependent manner. Thus, highly functional BAs can be generated by cellular reprogramming, suggesting a promising tailor-made cell therapy against metabolic disorders including type 2 diabetes mellitus. PMID- 26365512 TI - The Phosphatases STS1 and STS2 Regulate Hematopoietic Stem and Progenitor Cell Fitness. AB - FLT3 and c-KIT are crucial regulators of hematopoietic stem and progenitor cells. We investigated the role of STS1 and STS2 on FLT3 and c-KIT phosphorylation, activity, and function in normal and stress-induced hematopoiesis. STS1/STS2 deficient mice show a profound expansion of multipotent progenitor and lymphoid primed multipotent progenitor cells with elevated colony-forming capacity. Although long-term hematopoietic stem cells are not increased in numbers, lack of STS1 and STS2 significantly promotes long-term repopulation activity, demonstrating a pivotal role of STS1/STS2 in regulating hematopoietic stem and progenitor cell fitness. Biochemical analysis identified STS1/STS2 as direct phosphatases of FLT3 and c-KIT. Loss of STS1/STS2 induces hyperphosphorylation of FLT3, enhances AKT signaling, and confers a strong proliferative advantage. Therefore, our study reveals that STS1 and STS2 may serve as novel pharmaceutical targets to improve hematopoietic recovery after bone marrow transplantation. PMID- 26365513 TI - Accumulation of the Vitamin D Precursor Cholecalciferol Antagonizes Hedgehog Signaling to Impair Hemogenic Endothelium Formation. AB - Hematopoietic stem and progenitor cells (HSPCs) are born from hemogenic endothelium in the dorsal aorta. Specification of this hematopoietic niche is regulated by a signaling axis using Hedgehog (Hh) and Notch, which culminates in expression of Runx1 in the ventral wall of the artery. Here, we demonstrate that the vitamin D precursor cholecalciferol (D3) modulates HSPC production by impairing hemogenic vascular niche formation. Accumulation of D3 through exogenous treatment or inhibition of Cyp2r1, the enzyme required for D3 25 hydroxylation, results in Hh pathway antagonism marked by loss of Gli-reporter activation, defects in vascular niche identity, and reduced HSPCs. Mechanistic studies indicated the effect was specific to D3, and not active 1,25-dihydroxy vitamin D3, acting on the extracellular sterol-binding domain of Smoothened. These findings highlight a direct impact of inefficient vitamin D synthesis on cell fate commitment and maturation in Hh-regulated tissues, which may have implications beyond hemogenic endothelium specification. PMID- 26365514 TI - CPM Is a Useful Cell Surface Marker to Isolate Expandable Bi-Potential Liver Progenitor Cells Derived from Human iPS Cells. AB - To develop a culture system for large-scale production of mature hepatocytes, liver progenitor cells (LPCs) with a high proliferation potential would be advantageous. We have found that carboxypeptidase M (CPM) is highly expressed in embryonic LPCs, hepatoblasts, while its expression is decreased along with hepatic maturation. Consistently, CPM expression was transiently induced during hepatic specification from human-induced pluripotent stem cells (hiPSCs). CPM(+) cells isolated from differentiated hiPSCs at the immature hepatocyte stage proliferated extensively in vitro and expressed a set of genes that were typical of hepatoblasts. Moreover, the CPM(+) cells exhibited a mature hepatocyte phenotype after induction of hepatic maturation and also underwent cholangiocytic differentiation in a three-dimensional culture system. These results indicated that hiPSC-derived CPM(+) cells share the characteristics of LPCs, with the potential to proliferate and differentiate bi-directionally. Thus, CPM is a useful marker for isolating hiPSC-derived LPCs, which allows development of a large-scale culture system for producing hepatocytes and cholangiocytes. PMID- 26365515 TI - Comparison of cryoablation with 3D mapping versus conventional mapping for the treatment of atrioventricular re-entrant tachycardia and right-sided paraseptal accessory pathways. AB - Aim Transcatheter cryoablation is a well-established technique for the treatment of atrioventricular nodal re-entry tachycardia and atrioventricular re-entry tachycardia in children. Fluoroscopy or three-dimensional mapping systems can be used to perform the ablation procedure. The aim of this study was to compare the success rate of cryoablation procedures for the treatment of right septal accessory pathways and atrioventricular nodal re-entry circuits in children using conventional or three-dimensional mapping and to evaluate whether three dimensional mapping was associated with reduced patient radiation dose compared with traditional mapping. METHODS: In 2013, 81 children underwent transcatheter cryoablation at our institution, using conventional mapping in 41 children - 32 atrioventricular nodal re-entry tachycardia and nine atrioventricular re-entry tachycardia - and three-dimensional mapping in 40 children - 24 atrioventricular nodal re-entry tachycardia and 16 atrioventricular re-entry tachycardia. RESULTS: Using conventional mapping, the overall success rate was 78.1 and 66.7% in patients with atrioventricular nodal re-entry tachycardia or atrioventricular re entry tachycardia, respectively. Using three-dimensional mapping, the overall success rate was 91.6 and 75%, respectively (p=ns). The use of three-dimensional mapping was associated with a reduction in cumulative air kerma and cumulative air kerma-area product of 76.4 and 67.3%, respectively (p<0.05). CONCLUSIONS: The use of three-dimensional mapping compared with the conventional fluoroscopy guided method for cryoablation of right septal accessory pathways and atrioventricular nodal re-entry circuits in children was associated with a significant reduction in patient radiation dose without an increase in success rate. PMID- 26365516 TI - Blood-based gene expression profiling in castrate-resistant prostate cancer. AB - Castrate-resistant prostate cancer (CRPC), the most life-threatening form of prostate cancer, has recently been the focus of many successful new treatments. Contemporary trials highlight the heterogeneous prognosis of CRPC as overall survival times vary greatly across different patient sub-groups. As presented in BMC Medicine, Wang et al. identify a blood-based prognostic signature in CRPC. Their approach is notable for discovery and validation of a four-gene model based on a whole-blood expression signature sampled from three distinct clinical cohorts. Further, the marker selection process incorporates an understanding of biological pathways expressed in myeloid or lymphoid cells which may provide some insight into host-tumor interactions as reflected in the peripheral blood. While the study includes a multivariate analysis accounting for many important clinical variables, larger datasets with more complete clinical information and sufficient follow-up are needed to confirm the independent significance of the four-gene expression model in a way which may better inform the care of CRPC patients.Please see related article: http://www.biomedcentral.com/1741 7015/13/201 . PMID- 26365517 TI - Long-Chain Fatty Acids Elicit a Bitterness-Masking Effect on Quinine and Other Nitrogenous Bitter Substances by Formation of Insoluble Binary Complexes. AB - We have previously found that fatty acids can mask the bitterness of certain nitrogenous substances through direct molecular interactions. Using isothermal titration calorimetry, we investigated the interactions between sodium oleate and 22 bitter substances. The hydrochloride salts of quinine, promethazine, and propranolol interacted strongly with fatty acids containing 12 or more carbon atoms. The (1)H NMR spectra of these substances, obtained in the presence of the sodium salts of the fatty acids in dimethyl sulfoxide, revealed the formation of hydrogen bonds between the nitrogen atoms of the bitter substances and the carboxyl groups of the fatty acids. When sodium laurate and the hydrochloride salt of quinine were mixed in water, an equimolar complex formed as insoluble heterogeneous needlelike crystals. These results suggested that fatty acids interact directly with bitter substances through hydrogen bonds and hydrophobic interactions to form insoluble binary complexes that mask bitterness. PMID- 26365518 TI - TPH2 gene polymorphisms and bipolar disorder: A meta-analysis. AB - BACKGROUND: Disturbance of the serotonergic system contributes to the etiology of bipolar disorder (BD). Tryptophan hydroxylase-2 (TPH2) is an important rate limiting enzyme in the synthetic pathway for brain serotonin and has been suggested to play a role in BD. MATERIALS AND METHODS: We performed a systematic review and meta-analysis of all studies to date investigating the association studies between TPH2 and BD published before Aug 2014. All studies were abstracted from PubMed, Embase, HuGNet, and China National Knowledge Infrastructure (CNKI). Manuscripts and the supplementary documents of published genome-wide association studies in the field were also included. Effect sizes of independent loci that have been studied in more than three articles were synthesized using fixed and random effects models. RESULTS: Eight eligible studies addressed association between 63 TPH2 gene single nucleotide polymorphisms (SNPs) with BD, after linkage disequilibrium analysis, 12 independent SNPs were identified. Finally, three SNPs (rs4760820, rs11178998, and rs7954758) were found associated with BD using fixed effects models, and rs4760820 and rs11178998 were still associated with BD even with the more conservative random effects models. CONCLUSIONS: rs4760820 and rs11178998 were identified to have strong genetic association with BD in present study though confirmation will require larger sample sizes and in additional populations. PMID- 26365519 TI - Anisotropic electron-transfer mobilities in diethynyl-indenofluorene-dione crystals as high-performance n-type organic semiconductor materials: remarkable enhancement by varying substituents. AB - In this study, the electron-transfer properties of alkynylated indenofluorene diones with various substituents (SiMe3, SiPr3, and SiPh3) that function as n type organic semiconductors were comparatively investigated at the first principles DFT level based on the Marcus-Hush theory. The reorganization energies are calculated by the adiabatic potential-energy surface method, and the coupling terms are evaluated through a direct adiabatic model. The maximum value of the electron-transfer mobility of SiPr3 is 0.485 cm(2) V(-1) s(-1), which appears at the orientation angle of the conducting channel on the reference plane a-b near to 172 degrees /352 degrees . The predicted maximum electron mobility value of SiPr3 is nearly 26 times larger than that of SiPh3. This may be attributed to the largest number of intermolecular pi-pi interactions. In addition, the mobilities in all three crystals show remarkable anisotropic behavior. The calculated results indicate that SiPr3 could be an ideal candidate as a high-performance n type organic semiconductor material. Our investigations not only give us an opportunity to completely understand the charge transport mechanisms, but also provide guidelines for designing materials for electronic applications. PMID- 26365520 TI - The Efficacy of Primary Interventional Urethral Realignment for the Treatment of Traumatic Urethral Injuries. AB - PURPOSE: To evaluate the efficacy of primary interventional urethral realignment (PIUR) in patients with traumatic urethral injuries. MATERIALS AND METHODS: This retrospective study included 13 patients with traumatic urethral injuries who were treated with PIUR between September 2008 and February 2014. All 13 patients were men with the mean age of 56.3 years. Technical success rate of PIUR, time to PIUR, required procedure time, length of hospital stay, duration of urethral catheterization, and complications after PIUR were investigated. RESULTS: PIUR was technically successful in 12 of 13 patients (92.3%). The mean time from trauma to PIUR was 44 hours (range, 1-240 h). The mean procedure time was 20.2 minutes (range, 3-90 min). The median length of hospital stay was 15 days (range, 1-60 d). The mean duration of urethral catheterization after PIUR was 25 days (range, 9-65 d). There were no immediate complications related to PIUR, although 6 of 12 patients developed symptomatic urethral stricture after PIUR. The mean time to stricture development after PIUR was 4.3 months (range, 2-12 mo). Of the 6 patients, 2 were treated with endoscopic internal urethrotomy, and 4 were treated with interventional radiologic urethral balloon dilation. CONCLUSIONS: PIUR can be safe and effective for patients with traumatic urethral injuries. However, symptomatic stricture formation occurred in one-half of the successful realignment procedures. PMID- 26365521 TI - Leveraging BCS in Development: A Case Study. AB - In this work, we discuss leveraging the Biopharmaceutics Classification System (BCS) in the development of edivoxetine HCl, a selective norepinephrine reuptake inhibitor. First, the biopharmaceutical and in vivo data are presented and discussed. Solubility studies indicate that edivoxetine HCl meets the BCS "highly soluble" criteria. To determine permeability classifications, in vitro intestinal Caco-2 epithelial cell model with and without cyclosporin A (CsA), a common P glycoprotein (P-gp) inhibitor, were conducted. Pharmacokinetic (PK) data obtained across phase 1 and 2 clinical studies where single and multiple doses range from the lowest to the highest strength are presented. Neither the Caco-2 nor the in vivo data on their own were sufficient to conclusively classify edivoxetine as highly permeable. However, collectively the data were utilized to support high permeability and consequently BCS1 classification of edivoxetine HCl. BCS1 classification was leveraged throughout development to assess the risk associated with not conducting relative bioavailability (RBA) studies and avoiding bioequivalence (BE) studies. Examples are presented where formulation changes were made between phase I (drug in capsule/drug in bottle formulations) and phase II (tablet) trials in addition to phase III (tablet) and commercial (smaller tablet) without having to conduct any in vivo comparability studies. For the first change, BCS was leveraged to avoid conducting a RBA study even before obtaining official BCS classification. For the later change, official BCS1 classification was relied upon to avoid conducting a BE study. PMID- 26365523 TI - Erythrodermic psoriasis and severe hypotension requiring intensive care unit hospitalization: Poor treatment outcome as a result of poor adherence. AB - Psoriasis is closely associated with cardiovascular comorbidities. Poor adherence can affect both psoriasis outcomes and the effectiveness of treatment for cardiovascular comorbidities. We discuss a case of psoriasis medication nonadherence resulting in admission to the dermatology inpatient service for erythrodermic psoriasis. Administration of the patient's prescribed home antihypertensive regimen on admission resulted in a severe hypotension requiring transfer to the medical intensive care unit (ICU). This case illustrates the role of poor adherence in an erythrodermic flare of psoriasis; this case also illustrates how new-onset regimented adherence, in a formerly nonadherent patient, may result in life-threatening iatrogenic disease. PMID- 26365522 TI - Amino Acid Polymorphisms in Hepatitis C Virus Core Affect Infectious Virus Production and Major Histocompatibility Complex Class I Molecule Expression. AB - Amino acid (aa) polymorphisms in the hepatitis C virus (HCV) genotype 1b core protein have been reported to be a potent predictor for poor response to interferon (IFN)-based therapy and a risk factor for hepatocarcinogenesis. We investigated the effects of these polymorphisms with genotype 1b/2a chimeric viruses that contained polymorphisms of Arg/Gln at aa 70 and Leu/Met at aa 91. We found that infectious virus production was reduced in cells transfected with chimeric virus RNA that had Gln at aa 70 (aa70Q) compared with RNA with Arg at aa 70 (aa70R). Using flow cytometry analysis, we confirmed that HCV core protein accumulated in aa70Q clone transfected cells, and it caused a reduction in cell surface expression of major histocompatibility complex (MHC) class I molecules induced by IFN treatment through enhanced protein kinase R phosphorylation. We could not detect any effects due to the polymorphism at aa 91. In conclusion, the polymorphism at aa 70 was associated with efficiency of infectious virus production, and this deteriorated virus production in strains with aa70Q resulted in the intracellular accumulation of HCV proteins and attenuation of MHC class I molecule expression. These observations may explain the strain-associated resistance to IFN-based therapy and hepatocarcinogenesis of HCV. PMID- 26365524 TI - Therapy of hepatitis C by direct-acting anti-virals: the end of HCV in dialysis population? AB - The advent of direct-acting anti-viral (DAA) drugs is dramatically changing the treatment of hepatitis C virus (HCV) in patients with intact kidney function ('cure rates' >90% and infrequent adverse events). The information on efficacy and safety of DAAs for HCV therapy in patients with renal failure is limited. We have reviewed the available evidence regarding efficacy and safety of numerous DAAs (boceprevir, telaprevir, sofosbuvir, simeprevir, grazoprevir, elbasvir, ombitasvir, paritaprevir, ritonavir, dasabuvir, ledispavir, daclatasvir, asunaprevir, beclabuvir) in treating HCV-infected patients with renal impairment and/or end-stage renal disease. The major limitation of this review is the paucity of published data and its reliance on abstracts and product monographs. Preliminary data suggest that combination antiviral therapy (grazoprevir and elbasvir) is provided with great efficacy in patients with HCV genotype 1 and chronic kidney disease stage 4 or 5 including those on intermittent dialysis, SVR12, 99% (114/115), according to a per-protocol analysis. In another trial, patients with HCV genotype 1 and chronic kidney disease stage 4 or 5 were given the 3D regimen; an interim evaluation reported that all patients completing treatment to date had viral response (100%, 14/14) but data on sustained viral response are under evaluation. Treatments were generally well tolerated. PMID- 26365525 TI - Safety assessment and single-dose toxicokinetics of the flavouring agent myricitrin in Sprague-Dawley rats. AB - Myricitrin, a flavonol rhamnoside of myricetin extracted from the Chinese bayberry (Myrica rubra Siebold) plant, has been used in Japan since 1992 as a flavour modifier in snack foods, dairy products, and beverages. It is affirmed as generally recognised as safe (GRAS) by the US Flavour and Extract Manufacturer Association (FEMA) and is considered safe by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) at current estimated dietary exposures. In anticipation of expanded marketing, 97% pure myricitrin was fed to male and female Sprague Dawley rats at dietary concentrations of 0.5%, 1.5% and 5.0% in a 90-day toxicity study. There was increased food consumption and decreased body weight gain in males exposed to 5% myricitrin. Blood values were within laboratory reference ranges except for mean increases in basophils in low- and high-dose males and serum phosphorus in high-dose males. In the absence of abnormal clinical or histopathological changes, these changes are not considered adverse. Based on the 90-day rat toxicity study, the no observed adverse effect level (NOAEL) is 2926 mg kg(-1) day(-1) in males and 3197 mg kg(-1) day(-1) in females. Gavage administration of myricitrin resulted in blood levels of myricitrin within 1 h after single oral doses of 250, 500 or 1000 mg kg(-1) body weight, indicating direct absorption of the glycosylated form of this flavonoid. Blood levels of myricetin, a metabolite of myricitrin, were not present in rats dosed orally with 1.6 mg kg(-1) myricetin, but were present only at 12 or 24 h in one of five, in three of five, and in four of five rats dosed with 250, 500 and 1000 mg myricitrin kg(-1) body weight, respectively, possibly a result of hepatic conversion of myricitrin to myricetin and enterohepatic recirculation of the resulting myricetin. The current studies further support prior safety assessments of myricitrin as a food flavouring. PMID- 26365527 TI - Asthma medication use among late midlife U.S. Adults. AB - OBJECTIVE: Despite substantial prevalence of asthma, little is known about asthma in late midlife adults (50-64 years). The objective of this study was to examine the factors associated with the use of asthma medications among late midlife adults. METHODS: Pooled data were obtained from the 2006 to 2010 Medical Expenditure Panel Survey. Medication use outcome variables include: (a) daily use of a preventive asthma medication and (b) use of more than three canisters of rescue inhalers in last 3 months. The Andersen Behavioral Model of Health Services Utilization was used to guide the selection of independent variables. Descriptive, unadjusted and adjusted logistic regression analyses were performed. Point estimates were weighted to the US civilian population and variance estimates were adjusted to obtain appropriate standard errors. All analyses were conducted using STATA (version 12). RESULTS: A total of 1414 (weighted sample of 15,030,364) self-reported late midlife asthmatics were identified. About 31% of late midlife adults with asthma were using a preventive medication on a daily basis while 11% reported overusing acute medications. Adjusted analyses found that race, rurality and smoking were related to poor use of asthma medications among late midlife adults. CONCLUSION: Results suggest that asthma medication use is far from optimal among vulnerable groups of late midlife US adults. PMID- 26365528 TI - Octanuclear zinc phosphates with hitherto unknown cluster architectures: ancillary ligand and solvent assisted structural transformations thereof. AB - Structural variations in zinc phosphate cluster chemistry have been achieved through a careful selection of phosphate ligand, ancillary ligand, and solvent medium. The use of 4-haloaryl phosphates (X-dippH2) as phosphate source in conjunction with 2-hydroxypyridine (hpy) ancillary ligand in acetonitrile solvent resulted in the isolation of the first examples of octameric zinc phosphates [Zn8(X-dipp)8(hpy)4(CH3CN)2(H2O)2].4H2O (X = Cl 2, Br 3) and not the expected tetranuclear D4R cubane clusters. Use of 2,3-dihydroxypyridine (dhpy) as ancillary ligand, under otherwise similar reaction conditions with the same set of phosphate ligands and solvent, resulted in isolation of another type of octanuclear zinc phosphate clusters {[(Zn8(X-dipp)4(X dippH)4(dhpyH)4(dhpyH2)2(H2O)2].2solvent} (X = Cl, solvent = MeCN 4; Br, solvent = H2O 5), as the only isolated products. X-ray crystal diffraction studies reveal that 2 and 3 are octanuclear clusters that are essentially formed by edge fusion of two D4R zinc phosphates. Although 4 and 5 are also octanuclear clusters, they exhibit a completely different cluster architecture and have been presumably formed by the ability of 2,3-dihydroxypyridine to bridge zinc centers in addition to the X-dipp ligands. Dissolution of both types of octanuclear clusters in DMSO followed by crystallization yields D4R cubanes [Zn(X-dipp)(DMSO)]4 (X = Cl 6, Br 7), in which the ancillary ligands such as hpy, H2O, and CH3CN originally present on the zinc centers of 2-5 have been replaced by DMSO. DFT calculations carried out to understand the preference of Zn8 versus Zn4 clusters in different solvent media reveal that use of CH3CN as solvent favors the formation of fused cubanes of the type 2 and 3, whereas use of DMSO as the solvent medium promotes the formation of D4R structures of the type 6 and 7. The calculations also reveal that the vacant exocluster coordination sites on the zinc centers at the bridgehead positions prefer coordination by water to hpy or CH3CN. Interestingly, the initially inaccessible D4R cubanes [Zn(X-dipp)(hpy)]4.2MeCN (X = Cl 8, Br 9) could be isolated as the sole products from the corresponding DMSO-decorated cubanes 6 and 7 by combining them with hpy in CH3CN. PMID- 26365526 TI - Proteomics of yeast telomerase identified Cdc48-Npl4-Ufd1 and Ufd4 as regulators of Est1 and telomere length. AB - Almost 400 genes affect yeast telomere length, including Est1, which is critical for recruitment and activation of telomerase. Here we use mass spectrometry to identify novel telomerase regulators by their co-purification with the telomerase holoenzyme. In addition to all known subunits, over 100 proteins are telomerase associated, including all three subunits of the essential Cdc48-Npl4-Ufd1 complex as well as three E3 ubiquitin ligases. The Cdc48 complex is evolutionarily conserved and targets ubiquitinated proteins for degradation. Est1 levels are ~40 fold higher in cells with reduced Cdc48, yet, paradoxically, telomeres are shorter. Furthermore, Est1 is ubiquitinated and its cell cycle-regulated abundance is lost in Cdc48-deficient cells. Deletion of the telomerase-associated E3 ligase, Ufd4, in cdc48-3 cells further increases Est1 abundance but suppresses the telomere length phenotype of the single mutant. These data argue that, in concert with Ufd4, the Cdc48 complex regulates telomerase by controlling the level and activity of Est1. PMID- 26365529 TI - 13q31.1 microdeletion: A prenatal case report with macrocephaly and macroglossia. AB - We report on a female fetus with macrocephaly and macroglossia harbouring 13q31.1 microdeletion encompassing three genes: SPRY2, NDFIP2 and RBM26. NDFIP2 protein is involved in ubiquitination and in Ras/mitogen-activated protein kinase (MAPK) signaling pathways. SPRY2 protein is part of Sprout protein family and inhibits the Ras/MAPK pathways. Ras/MAPK pathway plays important role in complex cellular programs including cell differentiation and proliferation. Germline mutations in genes encoding protein involved in the MAPK cascade is responsible for a wide family of developmental disorders known as RASopathies. Some RASopathies, such as Costello syndrome, present a phenotype with (relative) macrocephaly as perinatal features. However, prenatal-onset macroglossia are generally absent in this syndrome but rather suggestive of the Beckwith-Wiedemann syndrome for which molecular testing were negative. Phenotype-genotype correlation with patients from DECIPHER defines NDFIP2 and SPRY2 as a possible candidate genes for a RASopathy potentially responsible for the clinical features in the fetus. Finally, this original case of 13q31.1 microdeletion underlines the importance of array-CGH in prenatal diagnosis with sonographic signs such as macroglossia and/or macrocephaly. In this case, genetic investigation should be not limited to the search of well-known genetic causes and other genomic microdeletions should be considered as alternative diagnoses for macroglossia. PMID- 26365530 TI - Spin transitions in bis(amidinato)-N-heterocyclic carbene iron(II) and iron(III) complexes. AB - In contrast to high spin pyridyl diimine iron(ii) dichloride complexes, analogous bis(amidinato)-N-heterocyclic carbene iron(ii) and iron(iii) complexes demonstrate complex magnetic behaviour. In the solid state, they are best described as intermediate spin complexes at low temperatures that demonstrate gradual spin transitions beginning near or below room temperature. Treating the bis(amidinato)-N-heterocyclic carbene iron(ii) complex with an aryl azide revealed enhanced reactivity compared to analogous complexes supported by pyridyl diimine ligands. PMID- 26365531 TI - Outcome of the Respiratory Syncytial Virus related acute lower respiratory tract infection among hospitalized newborns: a prospective multicenter study. AB - AIM: To determine the incidence and outcomes of respiratory syncytial virus (RSV) related acute lower respiratory tract infection (ALRI) including morbidity, nosocomial infection and mortality among newborn infants who were admitted to the neonatal intensive care units (NICUs). METHODS: A multicenter, prospective study was conducted in newborns who were hospitalized with community acquired or nosocomial RSV infection in 44 NICUs throughout Turkey. Newborns with ALRI were screened for RSV infection by Respi-Strip(r)-test. Main outcome measures were the incidence of RSV-associated admissions in the NICUs and morbidity, mortality and epidemics results related to these admissions. FINDINGS: The incidence of RSV infection was 1.24% (n: 250) and RSV infection constituted 19.6% of all ALRI hospitalizations, 226 newborns (90.4%) had community-acquired whereas 24 (9.6%) patients had nosocomial RSV infection in the NICUs. Of the 250 newborns, 171 (68.4%) were full-term infants, 183 (73.2%) had a BW >2500 g. RSV-related mortality rate was 1.2%. Four NICUs reported seven outbreaks on different months, which could be eliminated by palivizumab prophylaxis in one NICU. CONCLUSION: RSV associated ALRI both in preterm and term infants accounts an important percent of hospitalizations in the season, and may threat other high-risk patients in the NICU. PMID- 26365532 TI - Direct evidence on Ta-Metal Phases Igniting Resistive Switching in TaO(x) Thin Film. AB - A Ta/TaOx/Pt stacked capacitor-like device for resistive switching was fabricated and examined. The tested device demonstrated stable resistive switching characteristics including uniform distribution of resistive switching operational parameters, highly promising endurance, and retention properties. To reveal the resistive switching mechanism of the device, micro structure analysis using high resolution transmission electron microscope (HR-TEM) was performed. From the observation results, two different phases of Ta-metal clusters of cubic alpha-Ta and tetragonal beta-Ta were founded in the amorphous TaOx mother-matrix after the device was switched from high resistance state (HRS) to low resistance state (LRS) by externally applied voltage bias. The observed Ta metal clusters unveiled the origin of the electric conduction paths in the TaOx thin film at the LRS. PMID- 26365533 TI - Dual metal and Lewis base catalysis approach for asymmetric synthesis of dihydroquinolines and the alpha-arylation of aldehydes via N-acyliminium ions. AB - A dual catalytic system consisting of indium triflate and a chiral imidazolidinone catalyzes the asymmetric addition of aldehydes to N-acyl quinoliniums furnishing optically active dihydroquinolines in good yields and excellent selectivities. The products were further functionalized into optically active tetrahydroquinolines, quinolines and 6-oxa-2-aza-bicyclo[3.3.1]nonanes. PMID- 26365534 TI - Ketamine Increases Permeability and Alters Epithelial Phenotype of Renal Distal Tubular Cells via a GSK-3beta-Dependent Mechanism. AB - Ketamine, a dissociative anesthetic, is misused and abused worldwide as an illegal recreational drug. In addition to its neuropathic toxicity, ketamine abuse has numerous effects, including renal failure; however, the underlying mechanism is poorly understood. The process called epithelial phenotypic changes (EPCs) causes the loss of cell-cell adhesion and cell polarity in renal diseases, as well as the acquisition of migratory and invasive properties. Madin-Darby canine kidney cells, an in vitro cell model, were subjected to experimental manipulation to investigate whether ketamine could promote EPCs. Our data showed that ketamine dramatically decreased transepithelial electrical resistance and increased paracellular permeability and junction disruption, which were coupled to decreased levels of apical junctional proteins (ZO-1, occludin, and E cadherin). Consistent with the downregulation of epithelial markers, the mesenchymal markers N-cadherin, fibronectin, and vimentin were markedly upregulated following ketamine stimulation. Of the E-cadherin repressor complexes tested, the mRNA levels of Snail, Slug, Twist, and ZEB1 were elevated. Moreover, ketamine significantly enhanced migration and invasion. Ketamine-mediated changes were at least partly caused by the inhibition of GSK-3beta activity through Ser-9 phosphorylation by the PI3K/Akt pathway. Inhibiting PI3K/Akt with LY294002 reactivated GSK-3beta and suppressed ketamine-enhanced permeability, EPCs, and motility. These findings were recapitulated by the inactivation of GSK-3beta using the inhibitor 3F8. Taken together, these results provide evidence that ketamine induces renal distal tubular EPCs through the downregulation of several junction proteins, the upregulation of mesenchymal markers, the activation of Akt, and the inactivation of GSK-3beta. PMID- 26365536 TI - Motivational Interviewing Fidelity in a Community Corrections Setting: Treatment Initiation and Subsequent Drug Use. AB - INTRODUCTION: Although substance use is common among people in the U.S. criminal justice system, treatment initiation remains an ongoing problem. This study assessed the reliability and predictive validity of the Motivational Interviewing Treatment Integrity 3.1.1. (MITI) coding instrument in a community corrections sample. METHODS: We used data from 80 substance-using clients who were participating in a clinical trial of MI in a probation setting. We analyzed 124 MI counseling sessions using the MITI, a coding system for documenting MI fidelity. Bivariate associations and logistic regression modeling were used to determine if MI-consistent behaviors predicted substance use or treatment initiation at a 2-month follow-up. RESULTS: We found a high level of agreement between coders on behavioral utterance counts. Counselors met at least beginning proficiency on most MITI summary scores. Probationers who initiated treatment at 2-month follow-up had significantly higher ratings of clinician empathy and MI spirit than clients who did not initiate treatment. Other MITI summary scores were not significantly different between clients who had initiated treatment and those who did not. MI spirit and empathy ratings were entered into a forward logistic regression in which MI spirit significantly predicted 2-month treatment initiation (chi(2) (1)=4.10, p<.05, R(2)=.05) but counselor empathy did not. MITI summary scores did not predict substance use at 2-month follow-up. CONCLUSIONS: Counselor MI-consistent relational skills were an important predictor of client treatment initiation. Counselor behaviors such as empathy and MI spirit may be important for developing client rapport with people in a probation setting. PMID- 26365537 TI - Comprehensive Comparison of Various Techniques for the Analysis of Elemental Distributions in Thin Films: Additional Techniques. AB - In a recent publication by Abou-Ras et al., various techniques for the analysis of elemental distribution in thin films were compared, using the example of a 2 um thick Cu(In,Ga)Se2 thin film applied as an absorber material in a solar cell. The authors of this work found that similar relative Ga distributions perpendicular to the substrate across the Cu(In,Ga)Se2 thin film were determined by 18 different techniques, applied on samples from the same identical deposition run. Their spatial and depth resolutions, their measuring speeds, their availabilities, as well as their detection limits were discussed. The present work adds two further techniques to this comparison: laser-induced breakdown spectroscopy and grazing-incidence X-ray fluorescence analysis. PMID- 26365535 TI - Direct observation shows superposition and large scale flexibility within cytoplasmic dynein motors moving along microtubules. AB - Cytoplasmic dynein is a dimeric AAA(+) motor protein that performs critical roles in eukaryotic cells by moving along microtubules using ATP. Here using cryo electron microscopy we directly observe the structure of Dictyostelium discoideum dynein dimers on microtubules at near-physiological ATP concentrations. They display remarkable flexibility at a hinge close to the microtubule binding domain (the stalkhead) producing a wide range of head positions. About half the molecules have the two heads separated from one another, with both leading and trailing motors attached to the microtubule. The other half have the two heads and stalks closely superposed in a front-to-back arrangement of the AAA(+) rings, suggesting specific contact between the heads. All stalks point towards the microtubule minus end. Mean stalk angles depend on the separation between their stalkheads, which allows estimation of inter-head tension. These findings provide a structural framework for understanding dynein's directionality and unusual stepping behaviour. PMID- 26365540 TI - SI: Irreversible Electroporation (IRE). Introduction. PMID- 26365539 TI - Daily affective experiences predict objective sleep outcomes among adolescents. AB - Adolescence is a sensitive period for changes in both sleep and affect. Although past research has assessed the association between affect and sleep among adolescents, few studies have examined both trait (typical) and day-to-day changes in affect, and fewer still have specifically examined negative social evaluative emotions (e.g. embarrassment) in relation to sleep. Both between- and within-person variations in daily affect were examined in relation to four objectively-measured sleep outcomes (sleep hours; sleep latency; sleep efficiency; and length of wake bouts) among adolescents. Participants (N = 77 high-school students; 42.9% female; M = 14.37 years) wore an actiwatch and completed daily-diaries for 3 days. The results of hierarchical linear models (controlling for age, gender, race, ethnicity, parental employment status, income, puberty and caffeine) indicated that negative social evaluative emotions and high-arousal affective experiences generally predicted poor sleep outcomes, whereas low-arousal affective experiences were associated with good sleep outcomes. Specifically, at the person level, adolescents reporting higher negative social evaluative emotions had shorter average sleep hours, and those experiencing higher anxiety-nervousness had longer wake bouts. In addition, individuals experiencing more dysphoria (sad, depressed, lonely) had longer average sleep hours and shorter wake bouts, while those experiencing more calmness had shorter sleep latencies. At the within-person level, individuals had longer sleep latencies following days that they had experienced high-arousal positive affect (e.g. excitement), and had longer wake bouts following days they had experienced more negative social evaluative emotions. The results highlight the detrimental effects of negative social evaluative emotions and high-arousal affective states for adolescent sleep. PMID- 26365538 TI - A constitutively active G protein-coupled acetylcholine receptor regulates motility of larval Schistosoma mansoni. AB - The neuromuscular system of helminths controls a variety of essential biological processes and therefore represents a good source of novel drug targets. The neuroactive substance, acetylcholine controls movement of Schistosoma mansoni but the mode of action is poorly understood. Here, we present first evidence of a functional G protein-coupled acetylcholine receptor in S. mansoni, which we have named SmGAR. A bioinformatics analysis indicated that SmGAR belongs to a clade of invertebrate GAR-like receptors and is related to vertebrate muscarinic acetylcholine receptors. Functional expression studies in yeast showed that SmGAR is constitutively active but can be further activated by acetylcholine and, to a lesser extent, the cholinergic agonist, carbachol. Anti-cholinergic drugs, atropine and promethazine, were found to have inverse agonist activity towards SmGAR, causing a significant decrease in the receptor's basal activity. An RNAi phenotypic assay revealed that suppression of SmGAR activity in early-stage larval schistosomulae leads to a drastic reduction in larval motility. In sum, our results provide the first molecular evidence that cholinergic GAR-like receptors are present in schistosomes and are required for proper motor control in the larvae. The results further identify SmGAR as a possible candidate for antiparasitic drug targeting. PMID- 26365541 TI - Introduction to Irreversible Electroporation--Principles and Techniques. AB - Irreversible electroporation (IRE) is a novel nonthermal focal ablation technique that uses a series of brief but intense electric pulses delivered by paired electrodes into a targeted region of tissue, killing the cells by irreversibly disrupting cellular membrane integrity. Unlike other ablation methods, IRE has relatively little effect on connective tissues and nerves and has a low patient effect. The ability of IRE to achieve cell death immediately adjacent to large vessels without effect on the vessels themselves has raised the possibility of better treatment of advanced pancreatic cancer. Because of the low effect on the patient, IRE is well suited for use in conjunction with chemotherapeutic agents. The IRE effect is not uniform and is dependent on the intrinsic conductivity of the tissue, the number of pulses delivered, the current flow achieved, and the total time for the treatment. It is currently under investigation for a wide range of solid tumors and prostate cancer in humans and in animals in the breast, brain, and spinal cord. In clinical practice, IRE can be administered either percutaneously under imaging guidance or at open operation under direct vision. In animals there is some evidence of an immune response presumably due to exposure of the intracellular target material, resulting in a greater therapeutic effect. Unlike many other cancer treatments, IRE has been introduced for human clinical use at a very early stage of development of the technique and much of the basic understanding of how and when to use IRE is still under investigation. PMID- 26365542 TI - Irreversible Electroporation in the Treatment of Hepatocellular Carcinoma. AB - Irreversible electroporation (IRE) is a new nonthermal ablation modality that can be used to treat primary and metastatic lesions in the liver. This article describes the way IRE works, reviews safety and efficacy data, and presents strategies and recommendations for its use in everyday practice. In a series of liver lesions of various histologies, initial success was 100%; local recurrence rates were greater in larger lesions. In another series of hepatocellular carcinoma only, there was a 79% complete response rate overall and 93% in lesions less than 3 cm. Safety is comparable with those of other ablation modalities. IRE has advantages over other ablation modalities with comparable success rates. PMID- 26365543 TI - Liver Function Tests Following Irreversible Electroporation of Liver Tumors: Experience in 174 Procedures. AB - Irreversible electroporation (IRE) is a relatively new ablation modality that uses electric currents to cause cell death. It is commonly used to treat primary and secondary liver tumors in patients with normal liver function and preexisting cirrhosis. Retrospective analysis of 205 procedures sought to evaluate changes in liver function after IRE. Liver function tests (LFTs) results before and after IRE were evaluated from 174 procedures in 124 patients. Aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase (ALKP), and total bilirubin levels were analyzed. The study was Health Insurance Portability and Accountability Act compliant and institutional review board approved. Informed consent was waived. Changes in LFT results after IRE were compared with baseline and were followed up over time to see if they resolved. Changes were compared with volume of ablation. The greatest perturbations were in transaminase levels. The levels increased sharply within 24 hours after IRE in 129 (74.1%) procedures to extreme levels (more than 20 times the upper limit of normal in one third of cases). Resolution occurred in 95% and was demonstrated to have occurred by a mean of approximately 10 weeks, many documented as early as 7 days after procedure. ALKP levels elevated in 10% procedures, was slower to increase, and was less likely to resolve. Total bilirubin level demonstrated 2 different patterns of elevation--early and late--and similar to ALKP, it was more likely to remain elevated. There was no increased risk in patients with cirrhosis or cholangiocarcinoma. There was no correlation of levels with volume of ablation. IRE results in significant abnormalities in LFT results, but in most of the cases, these are self-limiting, do not preclude treatment, and are similar to the changes seen after radiofrequency and cryoablation in the liver. PMID- 26365544 TI - Focal Therapy of Prostate Cancer Using Irreversible Electroporation. AB - Focal therapy is a novel strategy that attempts to enhance the therapeutic ratio of standard radical treatment in prostate cancer. Irreversible electroporation (IRE) has some inherent characteristics that may be ideal for focal therapy. Precise confined ablation in the treatment area obtained via nonthermal damage with potential for minimal toxicity to surrounding structures may lead to optimal treatment with improved preservation of continence and erectile function. Initial data of focal IRE of the prostate are encouraging although further assessment is awaited to confirm these findings using robust methodology. In this article, we provide a comprehensive step-by-step description of our technique to deliver focal IRE in selected men with localized prostate cancer located in a discrete area of the prostate. PMID- 26365545 TI - Percutaneous Approach to Irreversible Electroporation of the Pancreas: Miami Protocol. AB - Despite advances in the treatment of unresectable locally advanced pancreatic cancer, outcomes remain poor. Irreversible electroporation is a nonthermal ablative modality whose role in the management of locally advanced pancreatic cancer is being studied. This review highlights patient selection, preparation, and follow-up as well as discusses the techniques to achieve safe and effective tumor ablation in this challenging location. PMID- 26365546 TI - Irreversible Electroporation for Colorectal Liver Metastases. AB - Image-guided tumor ablation techniques have significantly broadened the treatment possibilities for primary and secondary hepatic malignancies. A new ablation technique, irreversible electroporation (IRE), was recently added to the treatment armamentarium. As opposed to thermal ablation, cell death with IRE is primarily induced using electrical energy: electrical pulses disrupt the cellular membrane integrity, resulting in cell death while sparing the extracellular matrix of sensitive structures such as the bile ducts, blood vessels, and bowel wall. The preservation of these structures makes IRE attractive for colorectal liver metastases (CRLM) that are unsuitable for resection and thermal ablation owing to their anatomical location. This review discusses different technical and practical issues of IRE for CRLM: the indications, patient preparations, procedural steps, and different "tricks of the trade" used to improve safety and efficacy of IRE. Imaging characteristics and early efficacy results are presented. Much is still unknown about the exact mechanism of cell death and about factors playing a crucial role in the extent of cell death. At this time, IRE for CRLM should only be reserved for small tumors that are truly unsuitable for resection or thermal ablation because of abutment of the portal triad or the venous pedicles. PMID- 26365547 TI - Niche Applications of Irreversible Electroporation. AB - Irreversible electroporation (IRE) induces cell death by exposing it to high voltage, low-energy DC current pulses. The mechanism of cell death and healing is a departure from the other existing technologies such as radiofrequency ablation, microwave ablation, and cryoablation. These thermal ablative technologies have several applications in oncology but have limitations that have also been established. IRE has shown promise to overcome some of these limitations and has enabled the use of an ablative technology in treating lesions close to the bile ducts and vasculature and in organs such as the pancreas. This review highlights some of the niche applications of IRE and the data so far. PMID- 26365548 TI - Irreversible Electroporation of Hepatic and Pancreatic Malignancies: Radiologic Pathologic Correlation. AB - Irreversible electroporation (IRE) is a novel therapy that has shown to be a feasible and promising alternative to conventional ablative techniques when treating tumors near vital structures or blood vessels. The clinical efficacy of IRE has been evaluated using established imaging criteria. This study evaluates the histologic and imaging response of hepatic and pancreatic malignancies that were surgically resected after IRE. In total, 12 lesions ablated with IRE were included, including 3 pancreatic carcinomas, 5 primary tumors of the liver, and 4 metastatic tumors of the liver. The rate of complete response to IRE was 25% based on the histologic evaluation of the resected tumors. Although treatment related vessel wall changes were noted in several cases in histologic findings, there was no evidence of vascular luminal narrowing or obliteration in any of the specimens. The imaging response to IRE before surgical resection usually resulted in underestimation of disease burden when compared with the histologic response seen on the resected specimens. PMID- 26365549 TI - Integrative review of benefit levers' characteristics for system-wide spread of best healthcare practices. AB - AIM: To critically analyse the characteristics of the benefit levers that are required for effective system-wide spread of evidence-based practice. BACKGROUND: Evidence-based nursing practice is the cornerstone of quality patient care and merits system-wide implementation. Achieving system-wide spread of evidence-based innovations requires adoption of four benefit levers (the facilitators for spreading innovations), conceptualized by Edwards and Grinspun: alignment, leadership for change, permeation plans and supporting and reinforcing structures. Although these concepts have been explored and described in primary studies, they were only recently identified as benefit levers and their characteristics have not been reviewed in the context of health care using an integrative literature review. DESIGN: An integrative literature review using an adapted Whittemore and Knafl design. DATA SOURCES: A comprehensive search using multiple sites such as Scopus, EBSCOhost, ProQuest, ScienceDirect, Cochrane Library, Nexus, SAePublications, Sabinet, Google Scholar and grey literature was conducted (January-March 2012) and updated (December 2014). After reading the abstracts, titles and full-text articles, forty (N = 40) research and non research documents met the inclusion criteria. REVIEW METHODS: Thirty-five documents remained after critical appraisal. A systematic approach was used to analyse and synthesize the data and formulate concluding statements. RESULTS: Data revealed characteristics about alignment (personal, organizational and contextual attributes), permeation plans (phases), leadership for change (types, strategies, position, attitude and support) and supporting and reinforcing structures (types and requirements). CONCLUSION: Benefit levers should be used to promote the spread of evidence-based practices. However, more studies concerning benefit levers, specifically regarding 'alignment' and 'permeation plans', are required to promote system-wide spread of best healthcare practices. PMID- 26365550 TI - Restraint stress delays endometrial adaptive remodeling during mouse embryo implantation. AB - In mice, previously, we showed that restraint stress reduces the number of embryo implantation sites in the endometrium. Here, we hypothesized that the uterine microenvironment is altered by restraint stress and consequently is suboptimal for embryo implantation. On embryonic day 1 (E1), 60 of 154 pregnant CD1 mice underwent restraint stress (4 h), repeated daily to E3, E5 or E7 (n = 10 mice per group). Restraint stress decreased food intake and suppressed body weight gain on E3, E5 and E7. Restraint stress decreased the actual and relative weight (percent body weight) of uterus and ovary on E5 (by 14.9%, p = 0.03; 16.1%, p = 0.004) and E7 (by 16.8%, p = 0.03; 20.0%, p = 0.01). Morphologically, restraint stress decreased relative endometrial area (by 8.94-18.8%, p = 0.003-0.021) and uterine gland area (by 30.6%, p < 0.01 on E3 and 44.5%, p < 0.01 on E5). Immunohistochemistry showed that restraint stress decreased microvessel density (by 12.9-70.5%, p < 0.01) and vascular endothelial growth factor expression (by 14.6-45.9%, p = 0.007-0.02). Restraint stress decreased by 32.4-39.8% (p = 0.002 0.01) the mean optical density ratio for proliferating cell nuclear antigen/terminal deoxynucleotidyl transferase dUTP nick end labeling. Methyl thiazolyl tetrazolium assay showed a dose-dependent decrease in proliferative activity of endometrial stromal cells (from 52 of 154 pregnant E5 control mice) incubated with H2O2 (100-1000 MUM) in vitro. These findings supported the hypothesis that restraint stress negatively influences endometrial adaptive remodeling via an oxidative stress pathway, which resulted in fewer implantation sites. PMID- 26365551 TI - Piezotronic Effect in Strain-Gated Transistor of a-Axis GaN Nanobelt. AB - Due to the non-centrosymmetric crystal structures, wurtzite family semiconducting materials possess piezoelectric properties and exhibit polarizations along certain directions upon straining. Utilizing strain-induced piezoelectric polarization charges to modulate the energy band structures and thus to tune/control the transport processes of charge carriers is referred to as the piezotronic effect. Distinct from the previous studies of c-axis GaN nanowires, here we systematically study the piezotronic-effect-induced modifications of energy band structures and the corresponding influence on electronic transport properties of a-axis GaN nanobelts. The physical mechanism is carefully illustrated and further confirmed by theoretical simulations via finite element analysis. The spatial distributions of local carrier concentration and the energy band diagrams of a-axis GaN under various straining conditions are calculated. This work provides a thorough understanding of strain-gated transport properties of a-axis GaN piezotronic transistors and its future applications in semiconductor devices. PMID- 26365552 TI - Overflow in science and its implications for trust. AB - To explore increasing concerns about scientific misconduct and data irreproducibility in some areas of science, we interviewed a number of senior biomedical researchers. These interviews revealed a perceived decline in trust in the scientific enterprise, in large part because the quantity of new data exceeds the field's ability to process it appropriately. This phenomenon-which is termed 'overflow' in social science-has important implications for the integrity of modern biomedical science. PMID- 26365553 TI - [Pilot study evaluating the ratio of adverse drug reactions related to antimicrobials over their consumption in 2012-2013]. AB - OBJECTIVES: As part of our antimicrobials stewardship program, we were interested in the use of antimicrobials and prevalence of adverse drug reactions associated with the use of these drugs. METHODS: The retrospective and descriptive study was conducted over a one year-period between April 1st 2012 and March 31st 2013 in a mother-child Hospital. We determined the ratio: number of adverse drug reactions over 10,000 defined daily dose or 10,000days of therapy. We identified the ratios higher than average for which the confidence interval did not cross the calculated average. The severity of the adverse drug reactions was codified using the Common Terminology Criteria for Adverse Events. RESULTS: We found 570 adverse drug reactions including 100 (17.5%) adverse drug reactions related to antimicrobials during the financial year 2012-2013. It represented 96 patients. Thus, five antimicrobials, for which the confidence interval does not cross the calculated average value, may be targeted in risk management because they have a higher ratio than average: piperacillin (290 [113-722]), valganciclovir (244 [43 1260]), ceftriaxone (114 [56-234]), acyclovir (76 [26-220]) and liposomal amphotericin B (72 [20-258]). CONCLUSION: In a mother-child university hospital, we calculated a ratios of 19 [15-23] and 13 [10-15], it allows us targeting some antimicrobials in our approach to prevention and management of adverse drug reactions. PMID- 26365554 TI - Screening for nutritional rickets in a community. AB - Concern has been expressed about the rising incidence of nutritional rickets with its associated long-term sequelae in children globally. In order to address the condition worldwide, it is imperative that accurate figures of its incidence are available particularly in at-risk communities. In order to obtain these figures, various screening tools and diagnostic criteria have been used with no standardization of methodologies, resulting in varying prevalences which may under- or over-estimate the prevalence depending of the techniques used. This review discusses the advantages and disadvantages of various screening tests used to diagnose rickets in communities. Clinical signs characteristic of rachitic deformities have been used extensively, but are likely to over-estimate the prevalence and are dependent on the clinical skills of the observer. Biochemical tests such as alkaline phosphatase and 25-hydroxyvitamin D have also been proposed. There is no consensus on the usefulness of alkaline phosphatase as a screening tool, while there is general agreement that the measurement of vitamin D status is unhelpful in screening for rickets. Finally, the confirmation of the presence of active rickets in suspected infants and children is dependent on radiographic findings, although these may be less helpful in adolescents whose growth plates might be closed or nearly so. In order to obtain uniformity in screening for rickets globally, the is a need for consensus among public health specialists, paediatric endocrinologists and those interested in paediatric bone disease as to the best methods to be employed to determine the prevalence of rickets, particularly in communities with limited resources. PMID- 26365555 TI - The Vitamin D Assessment (ViDA) Study: design of a randomized controlled trial of vitamin D supplementation for the prevention of cardiovascular disease, acute respiratory infection, falls and non-vertebral fractures. AB - Observational studies have shown that low vitamin D status is associated with an increased risk of cardiovascular disease, acute respiratory infection, falls and non-vertebral fractures. We recruited 5110 Auckland adults, aged 50-84 years, into a randomized, double-blind, placebo-controlled trial to test whether vitamin D supplementation protects against these four major outcomes. The intervention is a monthly cholecalciferol dose of 100,000IU (2.5mg) for an estimated median 3.3 years (range 2.5-4.2) during 2011-2015. Participants were recruited primarily from family practices, plus community groups with a high proportion of Maori, Pacific, or South Asian individuals. The baseline evaluation included medical history, lifestyle, physical measurements (e.g. blood pressure, arterial waveform, lung function, muscle function), and a blood sample (stored at -80 degrees C for later testing). Capsules are being mailed to home addresses with a questionnaire to collect data on non-hospitalized outcomes and to monitor adherence and potential adverse effects. Other data sources include New Zealand Ministry of Health data on mortality, hospitalization, cancer registrations and dispensed pharmaceuticals. A random sample of 438 participants returned for annual collection of blood samples to monitor adherence and safety (hypercalcemia), including repeat physical measurements at 12 months follow-up. The trial will allow testing of a priori hypotheses on several other endpoints including: weight, blood pressure, arterial waveform parameters, heart rate variability, lung function, muscle strength, gait and balance, mood, psoriasis, bone density, and chronic pain. PMID- 26365556 TI - Novel analogs of 1,25-dihydroxyvitamin D2 combined with a plant polyphenol as highly efficient inducers of differentiation in human acute myeloid leukemia cells. AB - 1alpha,25-Dihydroxyvitamin D3 [1,25(OH)2D3] is known to act as a powerful differentiation inducer in various types of cancer cells, including acute myeloid leukemia (AML) cells. However, supraphysiological concentrations of 1,25(OH)2D3 required to induce terminal maturation of AML cells can cause lethal hypercalcemia in vivo. Here we characterized the differentiation-inducing effects of novel double-point modified analogs of 1,25-dihydroxyvitamin D2 [1,25(OH)2D2], PRI-5201 and PRI-5202 [Pietraszek et al. (2013) Steroids, 78:1003-1014], on HL60, U937 and MOLM-13 human AML cells in comparison with their direct precursors (PRI 1906 and PRI-1907, respectively) and 1,25(OH)2D3. The results demonstrated the following order of potency for the tested compounds: PRI-5202>PRI-1907>PRI 5201>PRI-1906>=1,25(OH)2D3, as determined by measuring the expression of cell surface markers of myeloid differentiation. Particularly, the sensitivity of different AML cell lines to PRI-5201 and PRI-5202 was 3-15-fold and 13-50 fold higher, respectively, compared to that of 1,25(OH)2D3. Importantly, all the analogs tested at 0.25-1nM concentrations retained the ability of 1,25(OH)2D3 to cooperate with the rosemary polyphenol carnosic acid, which strongly potentiated their prodifferentiation activity in a cell type-dependent manner. These synergistic effects were associated with increased induction of the vitamin D receptor (VDR) protein expression. However, surprisingly, carnosic acid was able to significantly enhance only 1,25(OH)2D3-induced transactivation of the direct repeat 3 (DR3)-type vitamin D response element (VDRE), whereas no such cooperation was seen with 1,25(OH)2D2 analogs. Furthermore, dose-response analysis revealed that 1,25(OH)2D3 was more efficacious than the analogs in inducing VDRE activation. This suggests that the superior prodifferentiation activity of the analogs, as compared to 1,25(OH)2D3, may be due to their potential for enhanced activation of the differentiation-related VDRE(s) that differ from the DR3-type element tested in this study. Collectively, the results demonstrate that the new double-point modified 1,25(OH)2D2 analogs are much stronger inducers of myeloid differentiation than 1,25(OH)2D3 and that their efficacy can be further enhanced by combination with plant polyphenols. These combinations warrant their further mechanistic and translational exploration in AML and other types of cancer. PMID- 26365557 TI - Loss of neurosteroid-mediated protection following stress during fetal life. AB - Elevated levels of neurosteroids during late gestation protect the fetal brain from hypoxia/ischaemia and promote neurodevelopment. Suppression of allopregnanolone production during pregnancy leads to the onset of seizure-like activity and potentiates hypoxia-induced brain injury. Markers of myelination are reduced and astrocyte activation is increased. The placenta has a key role in maintaining allopregnanolone concentrations in the fetal circulation and brain during gestation and levels decline markedly after both normal and preterm birth. This leads to the preterm neonate developing in a neurosteroid deficient environment between delivery and term equivalence. The expression of 5alpha reductases is also lower in the fetus prior to term. These deficiencies in neurosteroid exposure may contribute to the increase in incidence of the adverse patterns of behaviour seen in children that are born preterm. Repeated exposure to glucocorticoid stimulation suppresses 5alpha-reductase expression and allopregnanolone levels in the fetus and results in reduced myelination. Both fetal growth restriction and prenatal maternal stress lead to increased cortisol concentrations in the maternal and fetal circulation. Prenatal stress results in reduced expression of key GABAA receptor subunits that normally heighten neurosteroid sensitivity. These stressors also result in altered placental allopregnanolone metabolism pathways. These findings suggest that reduced neurosteroid production and action in the perinatal period may contribute to some of the adverse neurodevelopmental and behavioural outcomes that result from these pregnancy compromises. Studies examining perinatal steroid supplementation therapy with non-metabolisable neurosteroid analogues to improve these outcomes are warranted. PMID- 26365558 TI - The alkynylphosphonate analogue of calcitriol EM1 has potent anti-metastatic effects in breast cancer. AB - The active form of vitamin D3, calcitriol, plays a major role in maintaining calcium/phosphate homeostasis. In addition, it is a potent antiproliferative and prodifferentiating agent. However, when effective antitumor doses of calcitriol are employed, hypercalcemic effects are observed, thus precluding its therapeutic application. To overcome this problem, structural analogues have been designed with the aim at retaining or even increasing the antitumor effects while decreasing its calcemic activity. This report shows the biological evaluation of an alkynylphosphonate vitamin D less-calcemic analogue in a murine model of breast cancer. We demonstrate that this compound has potent anti-metastatic effects through its action over cellular migration and invasion likely mediated through the up-regulation of E-cadherin expression. Based on the current in vitro and in vivo results, EM1 is a promising candidate as a therapeutic agent in breast cancer. PMID- 26365559 TI - Treatment of vitamin D deficiency in cystic fibrosis. AB - Vitamin D deficiency occurs frequently in patients with cystic fibrosis (CF). Vitamin D is important for optimal mineralization of bone and may be important for other comorbidities commonly occurring in patients with CF. Vitamin D deficiency in patients with CF can arise from various causes including pancreatic exocrine insufficiency, lack of outdoor activity, and alterations of vitamin D metabolism. Due to fat malabsorption stemming from pancreatic insufficiency, higher oral doses of vitamin D are necessary to correct and maintain optimal vitamin D status in patients with CF. Recent studies have demonstrated that higher vitamin D status is associated with better lung function and that vitamin D therapy may help recovery from pulmonary exacerbations of CF. The mechanisms by which vitamin D may exert its beneficial actions in CF are unclear but likely related to the role vitamin D has in modulating the adaptive and innate immune response. Large randomized clinical studies to evaluate the potential role of vitamin D as adjunctive therapy in CF that goes beyond bone are necessary. PMID- 26365560 TI - Impact of bacteria in nasal aspirates on disease severity of bronchiolitis. AB - BACKGROUND: The effect of potentially pathogenic bacteria (PPB) on disease severity in patients with bronchiolitis is understudied. METHODS: This prospective study was carried out in the Children's Hospital of Soochow University during the 2012-2013 autumn and winter seasons. We enrolled consecutive children < 2 years of age hospitalized with an attending physician's diagnosis of bronchiolitis. Nasopharyngeal aspirate samples were tested for multiple respiratory viruses and cultured for Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus. RESULTS: In all, 30% (188 patients) were positive for Strep. pneumoniae, H. influenzae, M. catarrhalis, and Staph. aureus. Length of stay (LOS) for patients with PPB was 4.0 days (interquartile range, IQR, 25th-75th percentile: 3.0-6.0 days) versus 3.0 days (IQR, 3.0-5.0 days) for patients without PPB (p < 0.001). However, requirement and duration of supplemental oxygen were not significantly different between the two groups. H. influenzae was an independent risk factor for hospital LOS >= 5.0 days (adjusted odds ratio, 1.75; 95% confidence interval, 1.06-2.91). The presence of PPB was not associated with increased risk of supplemental oxygen requirement. CONCLUSIONS: Our study demonstrated that pediatricians should evaluate for PPB in patients with bronchiolitis, especially when they present with RSV infection, fever or percentage of neutrophils > 40%. The presence of H. influenzae in nasal aspirates is associated with longer LOS in patients with bronchiolitis. PMID- 26365561 TI - Cytotoxicity of pyrrolizidine alkaloid in human hepatic parenchymal and sinusoidal endothelial cells: Firm evidence for the reactive metabolites mediated pyrrolizidine alkaloid-induced hepatotoxicity. AB - Pyrrolizidine alkaloids (PAs) widely distribute in plants and can cause hepatic sinusoidal obstruction syndrome (HSOS), which typically presents as a primary sinusoidal endothelial cell damage. It is well-recognized that after ingestion, PAs undergo hepatic cytochromes P450 (CYPs)-mediated metabolic activation to generate dehydropyrrolizidine alkaloids (DHPAs), which are hydrolyzed to dehydroretronecine (DHR). DHPAs and DHR are reactive metabolites having same core pyrrole moiety, and can bind proteins to form pyrrole-protein adducts, which are believed as the primary cause for PA-induced HSOS. However, to date, the direct evidences supporting the toxicity of DHPAs and DHR in the liver, in particular in the sinusoidal endothelial cells, are lacking. Using human hepatic sinusoidal endothelial cells (HSEC) and HepG2 (representing hepatic parenchymal cells), cells that lack CYPs activity, this study determined the direct cytotoxicity of dehydromonocrotaline, a representative DHPA, and DHR, but no cytotoxicity of the intact PA (monocrotaline) in both cell lines, confirming that reactive metabolites mediate PA intoxication. Comparing with HepG2, HSEC had significantly lower basal glutathione (GSH) level, and was significantly more susceptible to the reactive metabolites with severer GSH depletion and pyrrole-protein adducts formation. The toxic potency of two reactive metabolites was also compared. DHPA was more reactive than DHR, leading to severer toxicity. In conclusion, our results unambiguously provided the first direct evidence for the critical role of DHPA and DHR in the reactive metabolites-mediated PA-induced hepatotoxicity, which occurs predominantly in HSEC due to severe GSH depletion and the significant formation of pyrrole-protein adducts in HSEC. PMID- 26365563 TI - Agreement Among Radiographs, Fluoroscopy and Bronchoscopy in Documentation of Airway Collapse in Dogs. AB - BACKGROUND: Airway collapse is a common finding in dogs with chronic cough, yet the diagnosis can be difficult to confirm without specialty equipment. HYPOTHESIS: Bronchoscopic documentation of tracheobronchial collapse will show better agreement with fluoroscopic imaging than with standard radiography. ANIMALS: Forty-two dogs prospectively evaluated for chronic cough. METHODS: In this prospective study, three-view thoracic radiographs were obtained followed by fluoroscopy during tidal respiration and fluoroscopy during induction of cough. Digital images were assessed for the presence or absence of collapse at the trachea and each lobar bronchus. Bronchoscopy was performed under general anesthesia for identification of tracheobronchial collapse at each lung segment. Agreement of imaging tests with bronchoscopy was evaluated along with sensitivity and specificity of imaging modalities as compared to bronchoscopy. RESULTS: Airway collapse was identified in 41/42 dogs via 1 or more testing modalities. Percent agreement between pairs of tests varied between 49 and 87% with poor moderate agreement at most bronchial sites. Sensitivity for the detection of bronchoscopically identified collapse was highest for radiography at the trachea, left lobar bronchi, and the right middle bronchus, although specificity was relatively low. Detection of airway collapse was increased when fluoroscopy was performed after induction of cough compared to during tidal respiration. CONCLUSIONS: Radiography and fluoroscopy are complementary imaging techniques useful in the documentation of bronchial collapse in dogs. Confirming the presence or absence of tracheal or bronchial collapse can require multiple imaging modalities as well as bronchoscopy. PMID- 26365564 TI - Alternate electrode placement for whole body and segmental bioimpedance spectroscopy. AB - Bioimpedance spectroscopy (BIS) is frequently used to monitor body fluid and body composition in healthy and clinical populations. BIS guidelines state that there should be no skin lesions at the site of electrodes, and if lesions are present, electrode positions should be changed. However, alternate electrode positions are yet to be reported. This study aimed to determine if ventral electrode placements were suitable alternatives for whole body and segmental BIS measurements. Three alternate electrode placements were assessed for whole body BIS using a combination of ventral hand and foot electrode placements. An alternate position was assessed for upper and lower body segmental BIS. The results demonstrated that for whole body BIS, if drive and sense electrodes on the hand are moved to ventral positions, but foot electrodes remain in standard positions, then whole body BIS variables were comparable to standard electrode positioning (percentage difference range = 0.01 to 1.65%, p = 0.211-0.937). The alternate electrode placement for upper limb segmental BIS, results in BIS variables that are comparable to that of the standard positioning (percentage difference range = 0.24-3.51%, p = 0.393-0.604). The alternate lower limb electrode position significantly altered all resistance and predicted BIS variables for whole body and lower limb segmental BIS (percentage difference range = 1.06-12.09%, p < 0.001). If wounds are present on the hands and/or wrist, then the alternate electrode position described in this study is valid, for whole body and upper limb segmental BIS. PMID- 26365562 TI - Promising toxicological biomarkers for the diagnosis of liver injury types: Bile acid metabolic profiles and oxidative stress marker as screening tools in drug development. AB - Promising biomarkers were identified in adult male Crl:CD (SD) rats for the screening of new chemical entities for their potential to cause liver injury. We examined the serum biochemistry, liver histopathology, and bile acid profiles by LC-MS/MS, and the mRNA expression of transporters and CYPs by an RT-PCR after the following treatments to male Crl:CD (SD) rats: (a) bile duct ligation (BDL); (b) a single oral dose of 150 mg/kg alpha-naphthylisothiocyanate (ANIT); and (c) repeated oral doses of a novel pyrrolidinecarboxylic acid derivative (abbreviated as PCA) at 30, 300, and 1000 mg/kg. The serum total bile acid levels and bilirubin concentrations were found to be elevated in all of the groups. However, the bile acid component profiles of the PCA group differed significantly from BDL and ANIT models: deoxycholic acid, lithocholic acid, and sulfated bile acids were upregulated in a dose-dependent manner only in the PCA group. In addition, the PCA group demonstrated high levels of hepatic heme oxygenase-1 expression, whereas the profiles of the mRNA levels of the hepatic transporters and CYPs of all groups were found to be similar. The histopathological findings, for both the BDL and ANIT groups, were of bile duct hyperplasia, hepatocyte degeneration and necrosis. In contrast, only bile duct hyperplasia and hepatocyte degeneration were observed in the PCA group, even at a lethal dose. These results indicated that PCA induced a cholestatic condition and the increase of oxidative stress markers implies that this will also lead hepatocellular injury. In conclusion, the serum bile acid components and sulfated bile acid levels, and the expression of oxidative stress markers could provide information that aids in the diagnosis of liver injury type and helps to elucidate the mechanisms of hepatotoxicity. These findings can be extrapolated into our clinical investigation. The analysis of these crucial biomarkers is likely to be a useful screening tool in the lead optimization phase of drug discovery. PMID- 26365566 TI - Changes in adipose tissue distribution during pregnancy estimated by ultrasonography. AB - OBJECTIVES: To investigate changes in adipose tissue distribution using ultrasonography of the subcutaneous and preperitoneal adipose tissue during pregnancy. METHODS: The sample included 400 pregnant women. The research was prospective and statistically designed as a controlled observation using a random sampling method. The adipose tissue was estimated by ultrasonography, five times during the pregnancy. The minimal thickness of the subcutaneous (Smin) and maximal thickness of the preperitoneal (Pmax) was obtained using the Suzuki method. Analysis of variance and the Bonferroni post hoc test for multiple comparisons were calculated. RESULTS: Smin values have a decreasing trend, while Pmax values have an increasing trend, independent of the body mass index. No statistically significant differences in Smin and Pmax have been noted for the observed week intervals until the 20th pregnanacy week. Smin values for the week intervals 12 and 16, as well as for the Pmax week intervals 12, 16, and 20, were statistically significantly different when compared with the values obtained for the week intervals 32 and 37 (p < 0.05). No difference has been observed between nulliparous and multiparous pregnancies. CONCLUSION: The adipose tissue distribution during pregnancy shows a tendency towards a decreased accumulation of subcutaneous and increased accumulation of preperitoneal adipose tissue. PMID- 26365567 TI - Preparation of a porphyrinic bis(pyridyl aldehyde) and its supramolecular complexes. AB - Shape-specific molecular assemblies require the preparation of the constituent building blocks with the necessary properties to bias exclusive formation of the proposed structures. In this work, a novel linear porphyrin dialdehyde was synthesised and used to assemble a supramolecular grid via Cu(i) heteroleptic phenanthroline/pyridyl imine complexation, and a tetrahedral cage via Fe(ii) pyridyl imine coordination. PMID- 26365568 TI - Risk analysis reveals global hotspots for marine debris ingestion by sea turtles. AB - Plastic marine debris pollution is rapidly becoming one of the critical environmental concerns facing wildlife in the 21st century. Here we present a risk analysis for plastic ingestion by sea turtles on a global scale. We combined global marine plastic distributions based on ocean drifter data with sea turtle habitat maps to predict exposure levels to plastic pollution. Empirical data from necropsies of deceased animals were then utilised to assess the consequence of exposure to plastics. We modelled the risk (probability of debris ingestion) by incorporating exposure to debris and consequence of exposure, and included life history stage, species of sea turtle and date of stranding observation as possible additional explanatory factors. Life history stage is the best predictor of debris ingestion, but the best-fit model also incorporates encounter rates within a limited distance from stranding location, marine debris predictions specific to the date of the stranding study and turtle species. There is no difference in ingestion rates between stranded turtles vs. those caught as bycatch from fishing activity, suggesting that stranded animals are not a biased representation of debris ingestion rates in the background population. Oceanic life-stage sea turtles are at the highest risk of debris ingestion, and olive ridley turtles are the most at-risk species. The regions of highest risk to global sea turtle populations are off of the east coasts of the USA, Australia and South Africa; the east Indian Ocean, and Southeast Asia. Model results can be used to predict the number of sea turtles globally at risk of debris ingestion. Based on currently available data, initial calculations indicate that up to 52% of sea turtles may have ingested debris. PMID- 26365570 TI - Epigenetic regulation of dorsal raphe GABA(B1a) associated with isolation-induced abnormal responses to social stimulation in mice. AB - In isolation-reared mice, social encounter stimulation induces locomotor hyperactivity and activation of the dorsal raphe nucleus (DRN), suggesting that dysregulation of dorsal raphe function may be involved in abnormal behaviors. In this study, we examined the involvement of dorsal raphe GABAergic dysregulation in the abnormal behaviors of isolation-reared mice. We also studied an epigenetic mechanism underlying abnormalities of the dorsal raphe GABAergic system. Both mRNA and protein levels of GABA(B1a), a GABA(B) receptor subunit, were increased in the DRN of isolation-reared mice, compared with these levels in group-reared mice. In contrast, mRNA levels for other GABAergic system-related genes (GABA(A) receptor alpha1, beta2 and gamma2 subunits, GABA(B) receptor 1b and 2 subunits, and glutamate decarboxylase 67 and 65) were unchanged. Intra-DRN microinjection of 0.06 nmol baclofen (a GABA(B) receptor agonist) exacerbated encounter-induced hyperactivity and aggressive behavior, while microinjection of 0.3 nmol phaclofen (a GABA(B) receptor antagonist) attenuated encounter-induced hyperactivity and aggressive behavior in isolation-reared mice. Furthermore, microinjection of 0.06 nmol baclofen elicited encounter-induced hyperactivity in group-reared mice. Neither baclofen nor phaclofen affected immobility time in the forced swim test and hyperactivity in a novel environment of isolation reared mice. Bisulfite sequence analyses revealed that the DNA methylation level of the CpG island around the transcription start site (TSS) of GABA(B1a) was decreased in the DRN of isolation-reared mice. Chromatin immunoprecipitation analysis showed that histone H3 was hyperacetylated around the TSS of GABA(B1a) in the DRN of isolation-reared mice. These findings indicate that an increase in dorsal raphe GABA(B1a) expression via epigenetic regulation is associated with abnormal responses to social stimulation such as encounter-induced hyperactivity and aggressive behavior in isolation-reared mice. PMID- 26365569 TI - Anxiolytic- and antidepressant-like effects of the methadone metabolite 2-ethyl-5 methyl-3,3-diphenyl-1-pyrroline (EMDP). AB - The enhancement of GABAergic and monoaminergic neurotransmission has been the mainstay of pharmacotherapy and the focus of drug-discovery for anxiety and depressive disorders for several decades. However, the significant limitations of drugs used for these disorders underscores the need for novel therapeutic targets. Neuronal nicotinic acetylcholine receptors (nAChRs) may represent one such target. For example, mecamylamine, a non-competitive antagonist of nAChRs, displays positive effects in preclinical tests for anxiolytic and antidepressant activity in rodents. In addition, nicotine elicits similar effects in rodent models, possibly by receptor desensitization. Previous studies (Xiao et al., 2001) have identified two metabolites of methadone, EMDP (2-ethyl-5-methyl-3,3 diphenyl-1-pyrroline) and EDDP (2-ethylidene-1,5-dimethyl-3,3 diphenylpyrrolidine), which are considered to be inactive at opiate receptors, as relatively potent noncompetitive channel blockers of rat alpha3beta4 nAChRs. Here, we show that these compounds are likewise highly effective blockers of human alpha3beta4 and alpha4beta2 nAChRs. Moreover, we show that they display relatively low affinity for opiate binding sites labeled by [(3)H]-naloxone. We then evaluated these compounds in rats and mice in preclinical behavioral models predictive of potential anxiolytic and antidepressant efficacy. We found that EMDP, but not EDDP, displayed robust effects predictive of anxiolytic and antidepressant efficacy without significant effects on locomotor activity. Moreover, EMDP at behaviorally active doses, unlike mecamylamine, did not produce eyelid ptosis, suggesting it may produce fewer autonomic side effects than mecamylamine. Thus, the methadone metabolite EMDP may represent a novel therapeutic avenue for the treatment of some affective disorders. PMID- 26365571 TI - Identification and Characterization of Mutations in the CLCN7 Gene in a Taiwanese Patient with Infantile Malignant Osteopetrosis. PMID- 26365572 TI - Drug therapy for overactive bladder. AB - Overactive bladder is a syndrome with a significant worldwide prevalence and economic impact on health resources. With ageing populations, the health burden of this condition that is more common in older people, is likely to increase. Following conservative therapies, medical management of overactive bladder is the mainstay of treatment, usually with antimuscarinic therapy. However, adherence is poor either due to adverse events or lack of efficacy of therapy. There have been recent developments that include a beta3-adrenoreceptor agonist and intradetrusor botulinum toxin, both of which are increasingly supported by a robust evidence base. Additionally there are emerging combination therapies and novel target agents that aim to treat this troubling syndrome. Alternative modes of delivery for existing therapies are also being explored with a view to improving adherence and efficacy. This article aims to outline the evidence base for existing and novel therapies as well as inform readers of emerging therapeutic options. PMID- 26365573 TI - Availability and scope of integrated screening for patients with Lynch syndrome. AB - OBJECTIVE: To assess the availability and capacity of US-based integrated centers for the management of Lynch syndrome. METHODS: A cross-sectional survey of practice patterns in the care of patients with Lynch syndrome was conducted at 33 National Cancer Institute-designated cancer centers in the USA from March 1 to June 1, 2013. Each cancer center was contacted by telephone and the caller used a uniform scripted greeting and survey format. RESULTS: All centers routinely recommended colonoscopy. Other recommended screening modalities were hysterectomy and bilateral salpingo-oophorectomy (29/33; 88%), endoscopy (27/33; 82%), urinalysis (23/33; 70%), endometrial sampling (21/33; 64%), dermatologic examination (19/32; 59%), pelvic ultrasonography (18/33; 55%), serum CA125 level (14/33; 42%), urine cytology (14/33; 42%), computed tomography (1/33; 3%), and magnetic resonance imaging (1/33; 3%). Each center had a multidisciplinary team but the composition varied. A designated team leader was present at 21 centers (64%). Having a team leader was associated with an increased likelihood of recommending endoscopy (P=0.04) and dermatologic surveillance (P=0.01). Only 23 centers (70%) had a system in place for communicating follow-up with patients. CONCLUSION: The lack of consensus in practice patterns recorded among participating centers probably reflected the limited existing evidence on the usefulness of most screening modalities. PMID- 26365574 TI - Focused Professional Performance Evaluation of a Radiologist--a Centers for Medicare and Medicaid Services and Joint Commission Requirement. AB - The Centers for Medicare and Medicaid Services require that all physicians undergo periodic performance evaluation to maintain hospital privileges. This evaluation is achieved through a screening ongoing professional practice evaluation, typically performed at 8-month intervals. When any concerns are raised through this evaluation, for all newly appointed physicians seeking hospital privileges or for physicians seeking privileges for new procedures, a focused professional practice evaluation must be undertaken. Although not well defined for any group of physicians, the process is especially challenging in the radiology environment, given the lack of a template for performing such an evaluation and ever-growing spectrum of diagnostic and image-guided procedures. The purpose of this review is to describe the requirements and various components of an focused professional practice evaluation process, as well as to provide examples of initiating events and suggestions for managing such events. Challenges inherent in the peer review process are also addressed. PMID- 26365576 TI - Femoral head and neck excision. The (most) unkindest cut of all? PMID- 26365575 TI - The Knee injury and Osteoarthritis Outcome Score reflects the severity of knee osteoarthritis better than the revised Knee Society Score in a general Japanese population. AB - PURPOSE: The purposes of this study were to examine population-based reference data for sex- and age-related differences between the 2011 revised Knee Society Score (KSS2011) and the Knee injury and Osteoarthritis Outcome Score (KOOS), to assess the correlation between those scores and radiographic knee osteoarthritis (OA), and to validate the use of the scores in a general Japanese population. METHODS: This cross-sectional study included 963 volunteers (368 males, 595 females; mean age: 54.7years). Participants were classified into five subgroups by age: under 40, 40s, 50s, 60s, and over 70years old. The KSS2011 and KOOS were determined using self-administered questionnaires. Weight-bearing radiographs of the bilateral knee were taken and graded according to the Kellgren-Lawrence (KL) scale. The mean KSS2011 and KOOS were compared among age groups. Correlations between the severity of knee OA and each score were assessed using multiple regression analysis. RESULTS: The overall KSS2011 tended to gradually decrease with age. Most subscales of the KSS2011 did not show sex-related differences. Similarly, the overall KOOS and all its subscales steadily decreased by approximately 20 points per decade with age. Most subscales of the KOOS were significantly decreased in females over 50. The KL grade was significantly related to both the overall KOOS (beta=-0.42, p<0.001) and KSS2011 (beta=-0.13, p=0.001), though the correlation to the KOOS was stronger. CONCLUSION: The overall KSS2011 and KOOS appear to decrease with age. In this population, the KOOS reflects the severity of knee OA better than the KSS2011. PMID- 26365577 TI - Intake of grape procyanidins during gestation and lactation impairs reverse cholesterol transport and increases atherogenic risk indexes in adult offspring. AB - Cardiovascular disease (CVD) is one of the most prevalent noncommunicable diseases in humans. Different studies have identified dietary procyanidins as bioactive compounds with beneficial properties against CVD by improving lipid homeostasis, among other mechanisms. The aim of this work was to assess whether grape seed procyanidin consumption at a physiological dose during the perinatal period could influence the CVD risk of the offspring. Wistar rat dams were treated with a grape seed procyanidin extract (GSPE; 25mg/kg of body weight per day) or vehicle during gestation and lactation. The adult male offspring of GSPE treated dams presented decreased high-density lipoprotein cholesterol (HDL-C) levels, increased total cholesterol-to-HDL-C ratios and an exacerbated fasting triglyceride-to-HDL-C ratios (atherogenic index of plasma) compared to the control group. Impaired reverse cholesterol transport (RCT) was evidenced by the accumulation of cholesterol in skeletal muscle and by decreased fecal excretion of cholesterol and bile acids, which was consistent with the observed mRNA down regulation of the rate-limiting enzyme in the hepatic bile acid synthesis pathway Cyp7A1. Conversely, GSPE programming also resulted in up-regulated gene expression of different key components of the RCT process, such as hepatic Npc1, Abcg1, Abca1, Lxra, Srebp2, Lcat, Scarb1 and Pltp, and the repression of microRNA miR-33a expression, a key negative controller of hepatic RCT at the gene expression level. Our results show that maternal intake of grape procyanidins during the perinatal period impacts different components of the RCT process, resulting in increased CVD risk in the adult offspring. PMID- 26365578 TI - Amino acid starvation induced by protease inhibition produces differential alterations in redox status and the thiol proteome in organogenesis-stage rat embryos and visceral yolk sacs. AB - The process of embryonic nutrition in rodent conceptuses during organogenesis has been shown to involve a dominant histiotrophic mechanism where essential developmental substrates and micronutrients are supplied as whole maternal proteins or cargoes associated with proteins. The histiotrophic nutrition pathways (HNP) responsible for uptake and initial processing of proteins across maternal-conceptal interfaces involve uptake via receptor mediated endocytosis and protein degradation via lysosomal proteolysis. Chemical inhibition of either process can lead to growth deficits and malformation in the embryo (EMB), but selective inhibition of either HNP component will elicit a different subset of developmental perturbations. In vitro, whole embryo culture exposure of GD10 or GD11 rat conceptuses to the natural protease inhibitor, leupeptin, leads to significant reductions in all measured embryonic growth parameters as well as a myriad of other effects. Leupeptin doses of 10 MUM or 20 MUM over a 26-h period (GD10-GD11) and 50 MUM over a 3 h pulse period produced significant decreases in the clearance of FITC-albumin from culture media. The near complete loss of acid soluble fluorescence and increased total visceral yolk sac (VYS) protein content confirmed the selective inhibition of proteolysis. Inhibition of lysosomal proteolysis thus deprives the developing EMB of essential nutrient amino acids producing conditions akin to amino acid starvation, but may also cause direct effects on pathways critical for normal growth and differentiation. Following leupeptin exposure for 26 or 6 h, total glutathione (GSH) concentrations dropped significantly in the VYS, but only slightly in yolk sac (YSF) and amniotic (AF) fluids. Cys concentrations increased in VYS and EMB, but dropped in YSF and AF fluids. Redox potentials (Eh) for the glutathione disulfide (GSSG)/glutathione (GSH) redox couple trended significantly toward the positive, confirming the net oxidation of conceptual tissues following leupeptin treatment. Analysis of the thiol proteome showed few alterations to specific pathways mapped to the Kyoto Encyclopedia of Genes and Genomes Pathway database, but did reveal significant increases in concentrations of proteins associated with glycolysis/gluconeogenesis in the VYS and decreased concentrations proteins associated with ribosome biogenesis and function in the EMB. A subset of proteins elevated by >2-23-fold in the VYS were identified as serum (blood) proteins and represent the maternal-side proteins captured by the VYS and which are not degraded in the lysosomes as a result of leupeptin's inhibitory action. The observed constellation of proteins decreased in the EMB by leupeptin represent proteins from several adaptive pathways that are commonly altered in responses to amino acid starvation. These studies show clear differential responses to protease inhibition in VYS and EMB during organogenesis and suggest the possibility for additional roles of redox regulation, cellular adaptations and metabolic insufficiency caused by protease inhibition. PMID- 26365579 TI - Glutamine supplementation attenuates ethanol-induced disruption of apical junctional complexes in colonic epithelium and ameliorates gut barrier dysfunction and fatty liver in mice. AB - Previous in vitro studies showed that glutamine (Gln) prevents acetaldehyde induced disruption of tight junctions and adherens junctions in Caco-2 cell monolayers and human colonic mucosa. In the present study, we evaluated the effect of Gln supplementation on ethanol-induced gut barrier dysfunction and liver injury in mice in vivo. Ethanol feeding caused a significant increase in inulin permeability in distal colon. Elevated permeability was associated with a redistribution of tight junction and adherens junction proteins and depletion of detergent-insoluble fractions of these proteins, suggesting that ethanol disrupts apical junctional complexes in colonic epithelium and increases paracellular permeability. Ethanol-induced increase in colonic mucosal permeability and disruption of junctional complexes were most severe in mice fed Gln-free diet. Gln supplementation attenuated ethanol-induced mucosal permeability and disruption of tight junctions and adherens junctions in a dose-dependent manner, indicating the potential role of Gln in nutritional intervention to alcoholic tissue injury. Gln supplementation dose-dependently elevated reduced-protein thiols in colon without affecting the level of oxidized-protein thiols. Ethanol feeding depleted reduced protein thiols and elevated oxidized protein thiols. Ethanol-induced protein thiol oxidation was most severe in mice fed with Gln-free diet and absent in mice fed with Gln-supplemented diet, suggesting that antioxidant effect is one of the likely mechanisms involved in Gln-mediated amelioration of ethanol-induced gut barrier dysfunction. Ethanol feeding elevated plasma transaminase and liver triglyceride, which was accompanied by histopathologic lesions in the liver; ethanol-induced liver damage was attenuated by Gln supplementation. These results indicate that Gln supplementation ameliorates alcohol-induced gut and liver injury. PMID- 26365580 TI - The beneficial effects of betaine on dysfunctional adipose tissue and N6 methyladenosine mRNA methylation requires the AMP-activated protein kinase alpha1 subunit. AB - The current study was conducted to determine whether betaine could improve fatty acid oxidation, mitochondrial function and N6-methyladenosine (m(6)A) mRNA methylation in adipose tissue in high-fat-induced mice and how AMP-activated protein kinase alpha1 subunit (AMPKalpha1) was involved. AMPKalpha1 knockout mice and wild-type mice were fed either a low-fat diet, high-fat diet or high-fat diet supplemented with betaine in the drinking water for 8weeks. Our results showed that mitochondrial genes (PGC1alpha) and beta-oxidation-related genes (CPT1a) at protein level were increased in wild-type mice supplemented with betaine when compared with those in mice with high-fat diet. Betaine also decreased FTO expression and improved m(6)A methylation in adipose tissue of wild-type mice with high-fat diet. However, betaine failed to exert the abovementioned effects in AMPKalpha1 knockout mice. In adipocytes isolated from mice with high-fat diet, betaine treatment increased lipolysis and lipid oxidation. Moreover, betaine decreased FTO expression and increased m(6)A methylation. However, while AMPKalpha1 was knockdown, no remarkable changes in adipocytes were observed under betaine treatment. Our results indicated that betaine supplementation rectified mRNA hypomethylation and high FTO expression induced by high-fat diet, which may contribute to its beneficial effects on impaired adipose tissue function. Our results suggested that the AMPKalpha1 subunit is required for the beneficial effects of betaine on dysfunctional adipose tissue and m(6)A methylation. These results may provide the foundation for a mechanism that links m(6)A methylation status in RNA, AMPKalpha1 phosphorylation and dysfunctional adipose tissue induced by high-fat diet. PMID- 26365581 TI - Activity of the antiestrogenic cajanin stilbene acid towards breast cancer. AB - Antiestrogenic therapy is a mainstay for estrogen receptor (ERalpha)-positive breast cancer. Due to the development of resistance to established antihormones such as tamoxifen, novel compounds are required. The low abundant cajanin stilbene acid (CSA) recently isolated by us from Pigeon Pea (Cajanus cajan) has structural similarities with estrogen. We analyzed the cytotoxic and anticancer activity of CSA in ERalpha-positive and -negative human breast cancer cells in vitro, in vivo and in silico. CSA exerts anticancer and antiestrogenic activities towards ERalpha-positive breast cancer, and it showed cytotoxicity towards tamoxifen-resistant MCF-7 cells, implying that CSA may be active against tamoxifen-resistant breast cancer cells. CSA showed low cytotoxicity in ERalpha negative breast tumor cells as expected. Comparable cytotoxicity was observed towards p53 negative MCF-7 cells, implying that CSA is effective independent of the p53 status. Xenografted MCF-7 cells in nude mice were better inhibited by CSA than by cyclophosphamide. Testing of 8 primary cell cultures derived from human breast cancer biopsies showed that cell cultures from ER-positive tumors were more sensitive than from ER-negative ones. Dose-dependent decrease in ERalpha protein levels was observed upon CSA treatment. Synergistic effect with tamoxifen was observed in terms of increased p53 protein level. CSA affected pathways related to p53, cancer and cell proliferation. Gene promoter analyses supported the ERalpha regulation. CSA bound to the same site as 17beta-estradiol and tamoxifen on ERalpha. In conclusion, CSA exerts its anticancer effects in ERalpha positive breast cancer cells by binding and inhibiting ERalpha. PMID- 26365582 TI - Income inequality, welfare, class and health: A comment on Pickett and Wilkinson, 2015. PMID- 26365583 TI - Pancreatic pathophysiology in cystic fibrosis. AB - The pancreas is one of the earliest, and most commonly affected, organs in patients with cystic fibrosis (CF). Studying the pathogenesis of pancreatic disease is limited in CF patients, due to its early clinical onset, co morbidities and lack of tissue samples from the early phases of disease. In recent years, several new CF animal models have been developed that have advanced our understanding of both CF exocrine and endocrine pancreatic disease. Additionally, these models have helped us to better define the influence of pancreatic lesions on CF disease progression in other organs, such as the gastrointestinal tract and lung. PMID- 26365584 TI - Self-reported depression and perceived financial burden among long-term rectal cancer survivors. AB - OBJECTIVES: Types of surgery for rectal cancer (RC), including permanent ostomy (PO) or temporary ostomy followed by anastomosis (TO) or initial anastomosis (AN), can affect psychological and financial well-being during active treatment. However, these relationships have not been well studied among long-term survivors (>=5 years post-diagnosis). METHODS: A mailed survey with 576 long-term RC survivors who were members of Kaiser Permanente was conducted in 2010-2011. Prevalence of current depression was ascertained using a score of <=45.6 on the Short Form-12 version 2 mental component summary. Perceived financial burden was assessed using a Likert scale ranging from 0 (none) to 10 (severe). Regression analyses were used to measure associations after adjustment for covariates. RESULTS: The overall prevalence of depression was 24% among RC survivors with the highest prevalence among those with a history of PO (31%). The adjusted odds of depression among TO and AN survivors were lower than that among PO survivors, 0.42 (CI95% 0.20-0.89) and 0.59 (CI95% 0.37-0.93), respectively. Twenty-two percent perceived moderate-to-high current financial burden (>=4 points). PO survivors also reported higher mean financial burden than AN survivors (2.6 vs. 1.6, respectively; p = 0.002), but perceived burden comparably to TO survivors (2.3). Self-reported depression was associated with higher perceived financial burden (p < 0.001); surgical procedure history did not modify this relationship. CONCLUSIONS: Depression was reported frequently among these long-term RC survivors, particularly among PO survivors. Depression was associated with greater perception of financial burden. Screening for depression and assessing financial well-being might improve care among long-term RC survivors.Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26365585 TI - Metabolic and process engineering of Clostridium cellulovorans for biofuel production from cellulose. AB - Production of cellulosic biofuels has drawn increasing attention. However, currently no microorganism can produce biofuels, particularly butanol, directly from cellulosic biomass efficiently. Here we engineered a cellulolytic bacterium, Clostridium cellulovorans, for n-butanol and ethanol production directly from cellulose by introducing an aldehyde/alcohol dehydrogenase (adhE2), which converts butyryl-CoA to n-butanol and acetyl-CoA to ethanol. The engineered strain was able to produce 1.42 g/L n-butanol and 1.60 g/L ethanol directly from cellulose. Moreover, the addition of methyl viologen as an artificial electron carrier shifted the metabolic flux from acid production to alcohol production, resulting in a high biofuel yield of 0.39 g/g from cellulose, comparable to ethanol yield from corn dextrose by yeast fermentation. This study is the first metabolic engineering of C. cellulovorans for n-butanol and ethanol production directly from cellulose with significant titers and yields, providing a promising consolidated bioprocessing (CBP) platform for biofuel production from cellulosic biomass. PMID- 26365586 TI - Effect of estrogen on the expression of GnRH and kisspeptin in the hypothalamus of rats during puberty. AB - The aim of this study was to assess whether changes in kisspeptin and GnRH levels could be attributed to sex steroids at puberty onset. We used the ovariectomy (OVX) model in rats treated with 17beta-estradiol (E2; OVX + E2), or oil (OVX + oil), and in intact rats treated with E2 (intact + E2) or oil only (intact + oil) to determine gene expression changes of Kiss1 and Gnrh1 in the hypothalamus and protein expression of kisspeptin and GnRH in the different areas of the hypothalamus. In the intact + E2 and OVX + E2 rats on the day of the onset of puberty, GnRH-immunoreactive (ir) cell numbers decreased (P < 0.05) in the arcuate nucleus but were increased in the preoptic area; Kisspeptin-ir cells increased (P < 0.05) in the arcuate nucleus, periventricular nucleus, and preoptic area; no difference (P > 0.05) was found in the paraventricularis nucleus for GnRH-ir or kisspeptin-ir cells. Additionally, levels of Kiss1 and Gnrh1 messenger RNA in the hypothalamus were significantly higher (P < 0.05) in the OVX + E2 or intact + E2 rats than in the OVX + oil or intact + oil animals, respectively. In the OVX + oil rats, OVX significantly increased (P < 0.05) levels of Gnrh1 and Kiss1 messenger RNA and the expression of GnRH and kisspeptin in the hypothalamus compared to intact + oil animals. These results suggest that kisspeptin and GnRH play major roles in modulating the activity of estrogen circuits at the onset of puberty. PMID- 26365587 TI - Treatment Efficacy and Safety During Plasma Exchange With Citrate Anticoagulation: A Randomized Study of 4 Versus 15% Citrate. AB - In plasma exchange (PE), contrary to dialysis, there is no ultrafiltration, and the volume of anticoagulant contributes to volume overload of the patient and might also reduce PE efficiency through dilution. To reduce the volume of citrate, we compared 4 and 15% citrate anticoagulation protocols in PE in a randomized study, aiming to evaluate PE efficacy, anticoagulation efficiency, and overall safety. In addition to standard biochemical analyses during PE treatments, the elimination rate (ER) of immunoglobulins was calculated to evaluate PE efficacy. Anticoagulation was evaluated by postfilter ionized calcium, visual evaluation of the extracorporeal system, and change in the sieving coefficient (SC) during PE. Accumulation of citrate was determined by calculating the total-to-ionized calcium ratio and measuring the citrate concentration after PE. One hundred forty procedures (70 in each group) were performed in 37 patients. The mean citrate infusion rate was 197 +/- 10 mL/h in the 4% and 59 +/- 5.5 mL/h in the 15% groups, respectively; the total volume of infused citrate was 502 +/- 77 mL versus 164 +/- 52 mL (P < 0.001). ER for immunoglobulin G (0.57 +/- 0.06 vs. 0.55 +/- 0.1, P = 0.18), M, and A were comparable. Ionized calcium was stable during the procedures, and there were no significant side effects. Although postfilter ionized calcium was on the upper limit of the target range (0.41 +/- 0.16 vs. 0.37 +/- 0.14 mmol/L, P = 0.38), the visual assessment score was excellent, and even a rise in SC was observed during the procedures in both groups. The total-to-ionized calcium ratio was increased in 20 versus 22% of procedures, and citrate concentrations after PE were also similar (1306 +/- 441 vs. 1263 +/- 405 MUmol/L). To conclude, we were unable to show superior PE efficacy in the 15% citrate group, but we significantly reduced the infused volume, which is important in patients with fluid overload. Both citrate protocols were found to provide excellent anticoagulation without significant metabolic disturbances or other side effects, confirming the safety of 15% citrate as anticoagulant during PE. PMID- 26365588 TI - Febuxostat-associated drug reaction with eosinophilia and systemic symptoms (DRESS). AB - WHAT IS KNOWN AND OBJECTIVE: Febuxostat is recommended as an alternative drug for gouty patients with a history of allopurinol hypersensitivity or carrying the HLA B*5801 allele. CASE SUMMARY: An 81-year-old man with the medical history of gout presented to our clinic with generalized rashes for 2 days. After taking febuxostat for 2 days, he developed generalized skin rash with high fever. Laboratory tests showed elevated liver enzymes and acute kidney injury. WHAT IS KNOWN AND OBJECTIVE: This is the first identified case of febuxostat-associated DRESS. Febuxostat should be withdrawn immediately when DRESS is observed to avoid further serious complications. PMID- 26365589 TI - A Community-Academic Partnered Grant Writing Series to Build Infrastructure for Partnered Research. AB - Grant writing is an essential skill necessary to secure financial support for community programs and research projects. Increasingly, funding opportunities for translational biomedical research require studies to engage community partners, patients, or other stakeholders in the research process to address their concerns. However, there is little evidence on strategies to prepare teams of academic and community partners to collaborate on grants. This paper presents the description and formative evaluation of a two-part community-academic partnered grant writing series designed to help community organizations and academic institutions build infrastructure for collaborative research projects using a partnered approach. The first phase of the series was a half-day workshop on grant readiness, which was open to all interested community partners. The second phase, open only to community-academic teams that met eligibility criteria, was a 12-week session that covered partnered grant writing for foundation grants and National Institutes of Health grants. Participants in both phases reported an increase in knowledge and self-efficacy for writing partnered proposals. At 1 year follow-up, participants in Phase 2 had secured approximately $1.87 million in funding. This community-academic partnered grant writing series helped participants obtain proposal development skills and helped community-academic teams successfully compete for funding. PMID- 26365590 TI - Directing-group-assisted copper-catalyzed oxidative esterification of phenols with aldehydes. AB - A directing-group-assisted copper-catalyzed oxidative esterification of phenols with aldehydes using TBHP as an oxidant was described. This methodology which showed the advantages of base, ligand free, short routes and functional group tolerance could be used as an alternative protocol for the classical esterification reactions. PMID- 26365591 TI - Cost analysis of vestibular schwannoma screening with contrast-enhanced magnetic resonance imaging in patients with asymmetrical hearing loss. AB - BACKGROUND: Vestibular schwannomas are a rare cause of asymmetrical hearing loss, and routine screening with magnetic resonance imaging can be costly. This paper reports results on vestibular schwannoma screening at our institution and compares the cost of screening to a utility of hearing benefit. METHOD: All screening examinations with magnetic resonance imaging performed for asymmetrical hearing loss between 2006 and 2011 were retrospectively reviewed. The cost per new vestibular schwannoma diagnosis was calculated. The cost per patient for those who benefitted from intervention was estimated based on rates of hearing preservation reported in the literature. RESULTS: Forty-five (4.3 per cent) of 1050 screening examinations with magnetic resonance imaging performed for asymmetrical hearing loss were positive for vestibular schwannoma, and the cost per new diagnosis was $11,436. The estimated screening cost per patient for those who benefitted from surgery or radiation was $147,030, while US federal compensation for unilateral hearing loss was $44,888. CONCLUSION: Although we achieved a lower screening cost per new diagnosis than reported in the current literature, there remains disparity between the screening cost per benefitted patient and the 'benefit' of hearing. PMID- 26365592 TI - Elephants born in the high stress season have faster reproductive ageing. AB - Senescent declines in reproduction and survival are found across the tree of life, but little is known of the factors causing individual variation in reproductive ageing rates. One contributor may be variation in early developmental conditions, but only a few studies quantify the effects of early environment on reproductive ageing and none concern comparably long-lived species to humans. We determine the effects of 'stressful' birth conditions on lifetime reproduction in a large semi-captive population of Asian elephants (Elephas maximus). We categorise birth month into stressful vs. not-stressful periods based on longitudinal measures of glucocorticoid metabolites in reproductive-aged females, which peak during heavy workload and the start of the monsoon in June August. Females born in these months exhibit faster reproductive senescence in adulthood and have significantly reduced lifetime reproductive success than their counterparts born at other times of year. Improving developmental conditions could therefore delay reproductive ageing in species as long-lived as humans. PMID- 26365593 TI - Increased CD38 expression on T lymphocytes as a marker of HIV dissemination into the central nervous system. AB - Cross-sectional analysis on 20 HIV-1 patients with neurological symptoms admitted to two infectious disease units. Cut-off of HIV-RNA (VL) was 20 copies/ml for plasma and cerebral spinal fluid (CSF). Flow cytometry was used to analyze the phenotype of circulating and CSF T lymphocytes. CD38 mean fluorescence intensity (MFI) was higher on circulating CD4+T lymphocytes from patients with VL>20 copies/ml in plasma (P=0.001) or CSF (P=0.001). The frequency of circulating CD8+CD38+T cells and CD38 MFI on these cells were higher in patients with VL>20 copies/ml than in those with undetectable plasma VL (P=0.030 and P=0.023). The frequency of CSF CD4+CD38+T, as well as their CD38 and CD95 MFI, were increased in patients with detectable than non-detectable plasma VL (P=0.01, P=0.03, and P=0.05). The % CD38+CD8+T in CSF correlated with time of virological suppression (rho=-0.462, P=0.040) and the CNS penetration-effectiveness (CPE) score (rho= 0.467, P=0.038). In conclusion, (a) the expression of CD38+ on both CD4+, CD8+T lymphocytes from peripheral blood and CSF discriminated between viremic and non viremic patients and (b) T cell activation/apoptosis markers inversely correlated with CPE to remark the importance for therapy to restore immunological functions. PMID- 26365594 TI - The safety of polymyxin antibiotics. AB - INTRODUCTION: The emergence of multidrug-resistant gram-negative bacteria has led to the increasing use of polymyxins. Nephrotoxicity and, to a lesser degree, neurotoxicity occur often during systemic polymyxin therapy. Scientific evidence regarding safety associated with polymyxins remains limited. AREAS COVERED: Case reports/case series, observational studies and clinical trials assessing safety and toxicity of polymyxins were critically reviewed. EXPERT OPINION: Polymyxins are drugs with a narrow therapeutic range. Nephrotoxicity is associated with both host factors and polymyxin exposure, and recent studies suggest that the relative risk of nephrotoxicity is similar for colistin and polymyxin B. Studies that have examined the safety of polymyxins have several limitations. Considering the available evidence, toxicities that may develop while on polymyxin therapy most often are mild to moderate in magnitude and reversible in nature. Strategies to minimize toxicity associated with polymyxins have evolved and include avoidance of toxic medications, careful dosing, use of critical care, therapeutic drug monitoring and development of polymyxin derivatives. However, given that polymyxin use has re-emerged in an era of increased antimicrobial resistance, the presence of other treatment modalities may be limited. Therefore, clinicians must consider overall risk to benefit ratio of continuing versus stopping polymyxin treatment and optimize minimization strategies to reduce polymyxin-induced toxicities. PMID- 26365595 TI - Early stage of vascular disease and diabetic kidney disease: an under-recognized entity. AB - Early stage of vascular disease and diabetic kidney disease (DKD stages 1 and 2) has been under-recognized, under common practice worldwide. The lack of sensitive diagnostic marker leads to late diagnosis and a progression of underlying vascular disease associated with chronic renal ischemia, which eventually intensifies the magnitude of DKD damage. Treatment at this late stage fails to correct the renal ischemia, or restore renal function, due to the altered vascular homeostasis associated with an impaired nitric oxide production. In contrast to the above information, early recognition of vascular disease and DKD with sensitive diagnostic markers would be able to implement an effective prevention of progression of vascular disease and DKD. Treatment at early stage under environment favorable for adequate vascular homeostasis is able to correct the renal ischemia and improve the renal function. PMID- 26365596 TI - The spectrum of neutrophilic dermatoses associated with monoclonal gammopathy: Association with IgA isotype and inflammatory profile. AB - BACKGROUND: Neutrophilic dermatoses refer to a group of cutaneous inflammatory disorders characterized by neutrophilic infiltration of the skin. Neutrophilic dermatoses have been reported in association with various conditions including autoimmune diseases, inflammatory bowel diseases, and neoplasia. In the later condition, myeloproliferative disorders and monoclonal gammopathy (monoclonal immunoglobulin [MIg]) are the most frequent. Only few data are available in case of neutrophilic dermatoses associated with MIg regarding the pathophysiology and the clinical outcome. OBJECTIVE: We sought to gain further insight into clinical and biological aspects of neutrophilic dermatoses associated with MIg. METHODS: We report a retrospective series of 26 patients with neutrophilic dermatoses associated with MIg focusing on clinical and biological aspects, with a study of a large panel of cytokines, chemokines, and adhesion molecules. RESULTS: This study reveals an association between MIg IgA isotype and neutrophilic dermatoses, and a specific inflammatory pattern including elevated interleukin 6, vascular endothelial growth factor, monocyte chemotactic protein-1, epidermal growth factor, and intercellular adhesion molecule-1. LIMITATIONS: This is a retrospective study from a single institution with a limited number of participants. CONCLUSION: Our data highlight a strong association between IgA isotype and neutrophilic dermatoses, and the existence of a specific inflammatory profile involving several molecules. PMID- 26365597 TI - Improvement of tuberous sclerosis complex (TSC) skin tumors during long-term treatment with oral sirolimus. AB - BACKGROUND: Oral mechanistic target of rapamycin inhibitors have been shown to reduce visceral tumor volume in patients with tuberous sclerosis complex (TSC). OBJECTIVE: We sought to evaluate the cutaneous response to oral sirolimus in patients with TSC and an indication for systemic treatment, including long-term effects. METHODS: A retrospective analysis of 14 adult patients with TSC prescribed sirolimus to treat lymphangioleiomyomatosis was performed. Serial photographs of angiofibromas, shagreen patches, and ungual fibromas taken before, during, and after the treatment period were blinded, then assessed using the Physician Global Assessment of Clinical Condition (PGA). Microscopic and molecular studies were performed on skin tumors harvested before and during treatment. RESULTS: Sirolimus significantly improved angiofibromas (median treatment duration 12 months; median PGA score 4.5 [range 1.5-5]; Wilcoxon signed rank test, P = .018) and shagreen patches (median treatment duration 10 months; median PGA score 4.5 [range 3.5-5]; Wilcoxon signed rank test, P = .039), whereas ungual fibromas improved in some patients (median treatment duration 6.5 months; median PGA score 4.66 [range 2.75-5]; Wilcoxon signed rank test, P = .109). Clinical, immunohistochemical, or molecular evidence of resistance was not observed (range 5-64 months of treatment). LIMITATIONS: This was a retrospective analysis limited to adult women with lymphangioleiomyomatosis. CONCLUSION: Oral sirolimus is an effective long-term therapy for TSC skin tumors, particularly angiofibromas, in patients for whom systemic treatment is indicated. PMID- 26365598 TI - GRP78 rescues the ABCG5 ABCG8 sterol transporter in db/db mice. AB - OBJECTIVE: Mice lacking leptin (ob/ob) or its receptor (db/db) are obese, insulin resistant, and have reduced levels of biliary cholesterol due, in part, to reduced levels of hepatic G5G8. Chronic leptin replacement restores G5G8 abundance and increases biliary cholesterol concentrations, but the molecular mechanisms responsible for G5G8 regulation remain unclear. In the current study, we used a series of mouse models to address potential mechanisms for leptin mediated regulation of G5G8. METHODS AND RESULTS: We acutely replaced leptin in ob/ob mice and deleted hepatic leptin receptors in lean mice. Neither manipulation altered G5G8 abundance or biliary cholesterol. Similarly, hepatic vagotomy had no effect on G5G8. Alternatively, G5G8 may be decreased in ob/ob and db/db mice due to ER dysfunction, the site of G5G8 complex assembly. Overexpression of the ER chaperone GRP78 using an adenoviral vector restores ER function and reduces steatosis in ob/ob mice. Therefore, we determined if AdGRP78 could rescue G5G8 in db/db mice. As in ob/ob mice, AdGRP78 reduced expression of lipogenic genes and plasma triglycerides in the db/db strain. Both G5 and G8 protein levels increased as did total biliary cholesterol, but in the absence of changes in G5 or G8 mRNAs. The increase in G5G8 was associated with increases in a number of proteins, including the ER lectin chaperone, calnexin, a key regulator of G5G8 complex assembly. CONCLUSIONS: Leptin signaling does not directly regulate G5G8 abundance. The loss of G5G8 in mice harboring defects in the leptin axis is likely associated with compromised ER function. PMID- 26365599 TI - Environment and host genotype determine the outcome of a plant-virus interaction: from antagonism to mutualism. AB - It has been hypothesized that plant-virus interactions vary between antagonism and conditional mutualism according to environmental conditions. This hypothesis is based on scant experimental evidence, and to test it we examined the effect of abiotic factors on the Arabidopsis thaliana-Cucumber mosaic virus (CMV) interaction. Four Arabidopsis genotypes clustering into two allometric groups were grown under six environments defined by three temperature and two light intensity conditions. Plants were either CMV-infected or mock-inoculated, and the effects of environment and infection on temporal and resource allocation life history traits were quantified. Life-history traits significantly differed between allometric groups over all environments, with group 1 plants tolerating abiotic stress better than those of group 2. The effect of CMV infection on host fitness (virulence) differed between genotypes, being lower in group 1 genotypes. Tolerance to abiotic stress and to infection was similarly achieved through life history trait responses, which resulted in resource reallocation from growth to reproduction. Effects of infection varied according to plant genotype and environment from detrimental to beneficial for host fitness. These results are highly relevant and demonstrate that plant viruses can be pleiotropic parasites along the antagonism-mutualism continuum, which should be considered in analyses of the evolution of plant-virus interactions. PMID- 26365600 TI - Secondary batteries with multivalent ions for energy storage. AB - The use of electricity generated from clean and renewable sources, such as water, wind, or sunlight, requires efficiently distributed electrical energy storage by high-power and high-energy secondary batteries using abundant, low-cost materials in sustainable processes. American Science Policy Reports state that the next generation "beyond-lithium" battery chemistry is one feasible solution for such goals. Here we discover new "multivalent ion" battery chemistry beyond lithium battery chemistry. Through theoretic calculation and experiment confirmation, stable thermodynamics and fast kinetics are presented during the storage of multivalent ions (Ni(2+), Zn(2+), Mg(2+), Ca(2+), Ba(2+), or La(3+) ions) in alpha type manganese dioxide. Apart from zinc ion battery, we further use multivalent Ni(2+) ion to invent another rechargeable battery, named as nickel ion battery for the first time. The nickel ion battery generally uses an alpha type manganese dioxide cathode, an electrolyte containing Ni(2+) ions, and Ni anode. The nickel ion battery delivers a high energy density (340 Wh kg(-1), close to lithium ion batteries), fast charge ability (1 minute), and long cycle life (over 2200 times). PMID- 26365601 TI - Prediction by (13)C NMR of regioselectivity in 1,3-dipolar cycloadditions of acridin-9-yl dipolarophiles. AB - Strong correlation was found between (13)C NMR chemical shifts of dipolarophilic CH=CH carbons and regioselectivity in 1,3-dipolar cycloadditions of new acridin-9 yl dipolarophiles with stable benzonitrile oxides (BNO). Accordingly, two starting dipolarophiles, (acridin-9-yl)-CH=CH-R (R = COOCH3 or Ph), reacted with three BNOs (2,4,6-trimethoxy, 2,4,6-trimethyl, and 2,6-dichloro) to give a mixture of two target isoxazoline regioisomers in which the acridine was bound either to isoxazoline C-4 carbon (4-Acr) or C-5 one (5-Acr). Methyl 3-(acridin-9 yl)propenoate afforded major 4-(acridin-9-yl)-isoxazoline-5-carboxylates (4-Acr) and minor 5-(acridin-9-yl)-4-carboxylates (5-Acr). 9-(2-Styryl)acridine regiospecifically afforded only 4-Acr cycloadducts. The ratios of regioisomers were compared with analogous reactions of acridin-4-yl dipolarophiles. Regioselectivity was dependent on a polarity of the CH=CH bond, donor effects in BNO, and stabilization by stacking of aromatic substituents in the products. PMID- 26365602 TI - When speech enhances Spatial Musical Association of Response Codes: Joint spatial associations of pitch and timbre in nonmusicians. AB - Previous studies have shown that the effect of the Spatial Musical Association of Response Codes (SMARC) depends on various features, such as task conditions (whether pitch height is implicit or explicit), response dimension (horizontal vs. vertical), presence or absence of a reference tone, and former musical training of the participants. In the present study, we investigated the effects of pitch range and timbre: in particular, how timbre (piano vs. vocal) contributes to the horizontal and vertical SMARC effect in nonmusicians under varied pitch range conditions. Nonmusicians performed a timbre judgement task in which the pitch range was either small (6 or 8 semitone steps) or large (9 or 12 semitone steps) in a horizontal and a vertical response setting. For piano sounds, SMARC effects were observed in all conditions. For the vocal sounds, in contrast, SMARC effects depended on pitch range. We concluded that the occurrence of the SMARC effect, especially in horizontal response settings, depends on the interaction of the timbre (vocal and piano) and pitch range if vocal and instrumental sounds are combined in one experiment: the human voice enhances the attention, both to the vocal and the instrumental sounds. PMID- 26365603 TI - Design and characterisation of miniaturised cavity-backed patch antenna for microwave hyperthermia. AB - PURPOSE: The aim of this study was to describe the design and characterisation of a miniaturised 434 MHz patch antenna enclosed in a metal cavity for microwave hyperthermia treatment of cancer. MATERIALS AND METHODS: Electromagnetic (EM) field distribution in the near field of a microstrip patch irradiating body tissue was studied using finite element method (FEM) simulations. Antenna miniaturisation was achieved through dielectric loading with very high permittivity, metal enclosure, patch folding and shorting post. Frequency dependent electrical properties of materials were incorporated wherever appropriate using dispersion model and measurements. Antenna return loss and specific absorption rate (SAR) at 434 MHz were measured on muscle phantoms for characterisation. RESULTS: The design was progressively optimised to yield a compact 434 MHz patch (22 mm * 8.8 mm * 10 mm) inside a metal cavity (40 mm * 12 mm) with integrated coupling water bolus (35 mm). The fabricated antenna with integrated water bolus was self resonant at 434 MHz without load, and has better than -10 dB return loss (S11) with 13-20 MHz bandwidth on two different phantoms. SAR at 434 MHz measured using an infrared (IR) thermal camera on split phantoms indicated penetration depth for -3 dB SAR as 8.25 mm compared to 8.87 mm for simulation. The simulated and measured SAR coverage along phantom depth was 3.09 cm(2) and 3.21 cm(2) respectively at -3 dB, and 6.42 cm(2) and 9.07 cm(2) respectively at -6 dB. SAR full width at half maximum (FWHM) at 5 mm and 20 mm depths were 54.68 mm and 51.18 mm respectively in simulation, and 49.47 mm and 43.75 mm respectively in experiments. Performance comparison of the cavity-backed patch indicates more than 89% co-polarisation and higher directivity which resulted in deeper penetration compared to the patch applicators of similar or larger size proposed for hyperthermia treatment of cancer. CONCLUSION: The fabricated cavity-backed applicator is self-resonant at 434 MHz with a negligible shift in resonance when coupled to different phantoms, Deltaf/f0 less than 1.16%. IR thermography-based SAR measurements indicated that the -3 dB SAR of the cavity backed aperture antenna covered the radiating aperture surface at 5 mm and 20 mm depths. It can be concluded that the compact cavity-backed patch antenna has stable resonance, higher directivity and low cross polarisation, and is suitable for design of microwave hyperthermia array applicators with adjustable heating pattern for superficial and/or deep tissue heating. PMID- 26365604 TI - Introducing readers' comments online. PMID- 26365605 TI - Type 2 diabetes and the skeleton: new insights into sweet bones. AB - Substantial evidence shows that skeletal fragility should be considered among the complications associated with type 2 diabetes. Individuals with type 2 diabetes have increased fracture risk, despite normal bone mineral density (BMD) and high BMI-factors that are generally protective against fractures. The mechanisms underlying skeletal fragility in diabetes are not completely understood, but are multifactorial and likely include effects of obesity, hyperglycaemia, oxidative stress, and accumulation of advanced glycation end products, leading to altered bone metabolism, structure, and strength. Clinicians should be aware that BMD measurements underestimate fracture risk in people with type 2 diabetes, and that new treatments for diabetes, with neutral or positive effects on skeletal health, might play a part in the management of diabetes in those at high risk of fracture. Data for the optimum management of osteoporosis in patients with type 2 diabetes are scarce, but in the absence of evidence to the contrary, physicians should follow guidelines established for postmenopausal osteoporosis. PMID- 26365606 TI - Bioabsorbable stenting in peripheral artery disease. AB - Arterial stenting has been broadly utilized for the management of peripheral arterial occlusive disease. The evolution of stent materials has led to the introduction of newer bioabsorbable scaffolds that have been extensively evaluated in the treatment of coronary artery disease. However, the utilization of bioabsorbable stents in the lower extremities remains challenging and has not been evaluated in the same degree. There are not many trials focusing on major outcomes of treatment with bioabsorbable stents or comparing them with other therapeutic choices such as surgery or angioplasty only. The aim of this review is to report current status on bioabsorbable stenting in peripheral artery disease treatment as well as to present the results of all major relevant trials. Moreover, future expectations and challenges with this type of stents are discussed as well. PMID- 26365607 TI - Percutaneous brachial artery access for coronary artery procedures: Feasible and safe in the current era. AB - BACKGROUND: Percutaneous vascular access for coronary intervention is currently achieved predominately via the radial route, the femoral route acting as a backup. Percutaneous trans-brachial access is no longer commonly used due to concerns about vascular complications. This study aimed to investigate the safety and feasibility of percutaneous brachial access when femoral and radial access was not possible. METHODS: This is a retrospective data analysis of patients who attended a single tertiary cardiology centre in the UK between 2005 and 2014 and had a coronary intervention (coronary angiogram or PCI) via the brachial route. The primary endpoints were procedural success and the occurrence of vascular complications. RESULTS: During the study period 26602 patients had a procedure (15655 underwent PCI and 10947 diagnostic angiography). Of these, 117 (0.44% of total) had their procedure performed via the brachial route. The procedure was successful in 96% (112/117) of cases. 13 (11%) patients experienced post procedural complications, of which 2 (1.7%) were serious. There were no deaths. CONCLUSION: Percutaneous trans-brachial arterial access is feasible with a high success rate and without evidence of high complication rate in a rare group of patients in whom femoral or sometimes radial attempts have failed. PMID- 26365608 TI - Intra-arterial vasodilators to prevent radial artery spasm: a systematic review and pooled analysis of clinical studies. AB - OBJECTIVES: The aim of this study is to review the available literature on the efficacy and safety of agents used for prevention of RAS. BACKGROUND: Different vasodilator agents have been used to prevent radial artery spasm (RAS) in patients undergoing transradial cardiac catheterization. METHODS: We included studies that evaluated any intra-arterial drug administered in the setting cardiac catheterization that was undertaken through the transradial access site (TRA). We also compared studies for secondary outcomes of major bleeding, procedure time, and procedure failure rate in setting of RAS prevention, patent hemostasis and radial artery occlusion. RESULTS: 22 clinical studies met the inclusion criteria. For placebo, RAS rate was 12% (4 studies, 638 participants), which was similar to 2.5mg of verapamil 12% (3 studies, 768 participants) but greater than 5mg of verapamil (4%, 2 studies, 497 participants). For nicorandil, there was a much higher RAS rate compared to placebo (16%, 3 studies, 447 participants). The lowest rates of RAS was found for nitroglycerin at both 100 MUg (4%) and 200 MUg (2%) doses, isosorbide mononitrate (4%) and nicardipine (3%). We found no information regarding the procedure failure rates, patent hemostasis, and radial artery occlusion in these studies. CONCLUSIONS: In this largest and up-to-date review on intra-arterial vasodilators use to reduce RAS, we have found that the verapamil at a dose of 5mg or verapamil in combination with nitroglycerine are the best combinations to reduce RAS. PMID- 26365609 TI - Variation in acoustic overstimulation changes tinnitus characteristics. AB - Tinnitus often occurs after exposure to loud noise. This raises the question of whether repeated exposure to noise increases the risk of developing tinnitus. We thus studied tinnitus development after repeated acoustic overstimulation using startle and auditory brainstem-response techniques applied to Mongolian gerbils. Noise with bandwidths ranging from 0.25 up to 0.5 oct were used for repeated acoustic overstimulation. Auditory brainstem response measurements revealed similar threshold shifts in both groups of up to about 30 dB directly after the acoustic overstimulation. We identified an upper limit in threshold values, which was independent of the baseline values before the noise exposure. Several weeks after the acoustic overstimulation, animals with the noise bandwidth of 0.25 oct showed a permanent threshold shift, while animals of the group with the 0.5-oct noise band featured only a temporary threshold shift. We thus conclude that the threshold shift directly after noise exposure cannot be used as an indicator for the upcoming threshold level several weeks later. By using behavioral measurements, we investigated the frequency-dependent development of tinnitus related changes in both groups and one group with 1-oct noise bandwidth. The number of animals that show tinnitus-related changes was highest in animals that received noise with the bandwidth 0.5 oct. This number was, in contrast to the number of animals in the 0.25-oct bandwidth, not significantly increased after repeated overstimulation. The frequency distribution of tinnitus-related changes ranged from 4 to 20 kHz. In the group with the narrow-band noise (0.25 oct) changes center at one frequency range from 10 to 12 kHz. In the group with the broader noise band (0.5 oct), however, two peaks at 8-10 kHz and at 16-18 kHz were found, which suggests that different mechanisms underlie the tinnitus development. PMID- 26365610 TI - Prenatal exposure to ethanol stimulates hypothalamic CCR2 chemokine receptor system: Possible relation to increased density of orexigenic peptide neurons and ethanol drinking in adolescent offspring. AB - Clinical and animal studies indicate that maternal consumption of ethanol during pregnancy increases alcohol drinking in the offspring. Possible underlying mechanisms may involve orexigenic peptides, which are stimulated by prenatal ethanol exposure and themselves promote drinking. Building on evidence that ethanol stimulates neuroimmune factors such as the chemokine CCL2 that in adult rats is shown to colocalize with the orexigenic peptide, melanin-concentrating hormone (MCH) in the lateral hypothalamus (LH), the present study sought to investigate the possibility that CCL2 or its receptor CCR2 in LH is stimulated by prenatal ethanol exposure, perhaps specifically within MCH neurons. Our paradigm of intraoral administration of ethanol to pregnant rats, at low-to-moderate doses (1 or 3g/kg/day) during peak hypothalamic neurogenesis, caused in adolescent male offspring twofold increase in drinking of and preference for ethanol and reinstatement of ethanol drinking in a two-bottle choice paradigm under an intermittent access schedule. This effect of prenatal ethanol exposure was associated with an increased expression of MCH and density of MCH(+) neurons in LH of preadolescent offspring. Whereas CCL2(+) cells at this age were low in density and unaffected by ethanol, CCR2(+) cells were dense in LH and increased by prenatal ethanol, with a large percentage (83-87%) identified as neurons and found to colocalize MCH. Prenatal ethanol also stimulated the genesis of CCR2(+) and MCH(+) neurons in the embryo, which co-labeled the proliferation marker, BrdU. Ethanol also increased the genesis and density of neurons that co-expressed CCR2 and MCH in LH, with triple-labeled CCR2(+)/MCH(+)/BrdU(+) neurons that were absent in control rats accounting for 35% of newly generated neurons in ethanol exposed rats. With both the chemokine and MCH systems believed to promote ethanol consumption, this greater density of CCR2(+)/MCH(+) neurons in the LH of preadolescent rats suggests that these systems function together in promoting alcohol drinking during adolescence. PMID- 26365613 TI - Comparison of echocardiographic findings with laboratory parameters in obese children. AB - Aim The purpose of our study was to evaluate the association between insulin resistance and left ventricular size and function in obese children. Material and methods A total of 79 cases aged 10-16 years and diagnosed with obesity and 79 healthy and non-obese cases as controls were included in the study. Patient and control groups were divided into three groups in terms of age as group 1 (10-12 years), group 2 (12-14 years), and group 3 (14-16 years). Fasting blood glucose, lipid profile, and fasting insulin levels of the cases were assessed. Mitral valve E and A waves, left ventricular ejection fraction, fractional shortening, end-diastolic and end-systolic diameters, left atrium diameter, and septal wall thickness were measured using echocardiography. RESULTS: Measurements of septal diastolic thicknesses, left atrium diameter, and left ventricular end-systolic diameter of all the three groups obtained by echocardiography were statistically higher compared with the controls. In all the patient groups, the mitral valve E/A ratio was >1. In groups 2 and 3, there was a positive correlation between fasting insulin levels and HOMA-IR and left ventricular end-systolic diameter, end-diastolic diameter, and septal systolic and diastolic wall thicknesses. CONCLUSION: In paediatric obesity, identification of early cardiac changes will be significant in allowing early diagnosis and treatment of cardiovascular diseases. PMID- 26365611 TI - Altered hippocampal plasticity by prenatal kynurenine administration, kynurenine 3-monoxygenase (KMO) deletion or galantamine. AB - Glutamate receptors sensitive to N-methyl-D-aspartate (NMDA) are involved in embryonic brain development but their activity may be modulated by the kynurenine pathway of tryptophan metabolism which includes an agonist (quinolinic acid) and an antagonist (kynurenic acid) at these receptors. Our previous work has shown that prenatal inhibition of the pathway produces abnormalities of brain development. In the present study kynurenine and probenecid (both 100mg/kg, doses known to increase kynurenic acid levels in the brain) were administered to female Wistar rats on embryonic days E14, E16 and E18 of gestation and the litter was allowed to develop to post-natal day P60. Western blotting revealed no changes in hippocampal expression of several proteins previously found to be altered by inhibition of the kynurenine pathway including the NMDA receptor subunits GluN1, GluN2A and GluN2B, as well as doublecortin, Proliferating Cell Nuclear Antigen (PCNA), sonic hedgehog and unco-ordinated (unc)-5H1 and 5H3. Mice lacking the enzyme kynurenine-3-monoxygenase (KMO) also showed no changes in hippocampal expression of several of these proteins or the 70-kDa and 100-kDa variants of Disrupted in Schizophrenia-1 (DISC1). Electrical excitability of pyramidal neurons in the CA1 region of hippocampal slices was unchanged, as was paired pulse facilitation and inhibition. Long-term potentiation was decreased in the kynurenine-treated rats and in the KMO(-/-) mice, but galantamine reversed this effect in the presence of nicotinic receptor antagonists, consistent with evidence that it can potentiate glutamate at NMDA receptors. It is concluded that interference with the kynurenine pathway in utero can have lasting effects on brain function of the offspring, implying that the kynurenine pathway is involved in the regulation of early brain development. PMID- 26365614 TI - Identification and Quantitation of 2-Acetyl-1-pyrroline in Manuka Honey (Leptospermum scoparium). AB - Manuka honey from New Zealand is known for its exceptional antibacterial activity, which is due to high amounts of the 1,2-dicarbonyl compound methylglyoxal (MGO). MGO in manuka honey is formed via non-enzymatic dehydration from dihydroxyacetone (DHA) during honey maturation. MGO and DHA are highly reactive substances, leading to a variety of unique chemical reactions. During Strecker reaction between proline and MGO, 2-acetyl-1-pyrroline (2-AP), an important aroma compound, is formed. Using liquid-liquid extraction and gas chromatography-mass spectrometry analysis, 2-AP was identified unambiguously in manuka honey for the first time. Quantitation was carried out via external matrix calibration, using a synthetic 2-AP standard and artificial honey. The 2-AP concentration in 11 commercial samples of manuka honey ranged from 0.08 to 0.45 mg/kg. For manuka honey samples containing MGO in concentrations above 250 mg/kg, significantly higher amounts of 2-AP were found when compared to non-manuka honeys. When high amounts of MGO were artificially added to non-manuka multifloral honey, an increase of the 2-AP concentration from 0.07 to 0.40 mg/kg after 12 weeks of storage at 37 degrees C was observed, concomitant with a significant increase in the concentration of 5-hydroxymethylfurfural (HMF). No increase of 2-AP was found during storage at ambient temperature. 2-AP together with MGO can be a suitable parameter for the quality control of manuka honey. PMID- 26365612 TI - EBV and vitamin D status in relapsing-remitting multiple sclerosis patients with a unique cytokine signature. AB - Multiple sclerosis, a debilitating autoimmune and inflammatory disease of the central nervous system, is associated with both infectious and non-infectious factors. We investigated the role of EBV infection, vitamin D level, and cytokine signature in MS patients. Molecular and serological assays were used to investigate immune biomarkers, vitamin D level, and EBV status in 83 patients with relapsing-remitting multiple sclerosis and 62 healthy controls. In total, 98.8 % of MS patients showed a history of EBV exposure compared to 88.6 % in the healthy group (p = 0.005). EBV DNA load was significantly higher in MS patients than healthy subjects (p < 0.0001). Using a panel of biomarkers, we found a distinct transcriptional signature in MS patients compared to the healthy group with mRNA levels of CD73, IL-6, IL-23, IFN-gamma, TNF-alpha, IL-15, IL-28, and IL 17 significantly elevated in MS patients (p < 0.0001). In contrast, the mRNA levels for TGF-beta, IDO, S1PR1, IL-10, and CCL-3 were significantly lower in MS patients compared to healthy controls (p < 0.0001). No significant differences were found with the mRNA levels of IL-13, CCL-5, and FOXP3. Interestingly, in MS patients we found an inverse correlation between vitamin D concentration and EBV load, but not EBNA-1 IgG antibody levels. Our data highlight biomarker correlates in MS patients together with a complex interplay between EBV replication and vitamin D levels. PMID- 26365615 TI - Replica exchange reactive molecular dynamics simulations of initial reactions in zeolite synthesis. AB - Molecular simulation is a promising tool for the study of zeolite formation. However, sufficient sampling remains a grand challenge for the practical use of molecular simulation for this purpose. Here, we investigate the initial stage of zeolite synthesis under realistic conditions by using the replica-exchange method and the ReaxFF reactive force field. After a total simulation time of 480 ns, both energetic and structural properties approach convergence. Analyses of data collected at 600 K show that the inorganic structure directing agent NaOH promotes the aggregation of silicate, the formation of branched Si atoms and the formation of 5-membered rings. With the trajectories collected simultaneously at different temperatures, the effect of temperature is discussed. PMID- 26365616 TI - First records of Hippocampus algiricus in the Canary Islands (north-east Atlantic Ocean) with an observation of hybridization with Hippocampus hippocampus. AB - Morphometric and genetic analyses confirmed the first records of the West African seahorse Hippocampus algiricus at Gran Canaria Island (north-east Atlantic Ocean), and also the first evidence of interspecific hybridization in seahorses. These results provide additional data on the distribution of H. algiricus that may help to establish future conservation strategies, and uncover a new potential sympatric scenario between H. algiricus and Hippocampus hippocampus. PMID- 26365617 TI - Weekend versus Weekday Admission and In-Hospital Mortality from Ischemic Stroke in Japan. AB - BACKGROUND: The initial treatment of acute ischemic stroke critically affects patient outcome. Patient outcome may also be associated with the day of hospital admission due to differences in the number of the hospital staff between weekdays and weekends. We aimed to assess the effect of weekend admission on in-hospital mortality among patients with ischemic stroke in Japan. METHODS: We analyzed patients with ischemic stroke from a large nationwide administrative dataset. The patients were grouped according to the treatment ward to which they were initially admitted: a general medical ward (GMW) or an intensive or stroke care unit (S-ICU). The primary outcome, in-hospital mortality, was compared between the patients admitted on a weekday versus weekend according to the initial treatment ward. A generalized estimated equation was applied for multivariate analysis. RESULTS: In total, 47,885 patients were included in the study. Of these patients, 32.0% were admitted to an S-ICU and 27.8% were admitted to a GMW on a weekend. The estimated in-hospital mortality rate was significantly higher among the patients admitted to a GMW on a weekend compared with those admitted on a weekday (7.9% versus 7.0%), but this difference was not significant after adjusting for the patients' background characteristics. The estimated in-hospital mortality rates of the patients admitted to an S-ICU were similar between weekend and weekday admissions (10.0% versus 9.9%). CONCLUSIONS: No significant effect of weekend admission in-hospital mortality was observed in our study population regardless of the initial treatment ward. PMID- 26365618 TI - No Evidence of Increased Risk of Stroke with Consumption of Refined Grains: A Meta-analysis of Prospective Cohort Studies. AB - OBJECTIVES: Results of the relationships between dietary consumption of refined grains and the risk of stroke are mixed. This study was based on a meta-analysis of prospective cohort studies. METHODS: We systematically searched the MEDLINE (from January 1, 1966) and EMBASE (from January 1, 1974) databases up to November 30, 2014. Random-effects models were used to calculate summary relative risks (SRRs) and 95% confidence intervals (CIs). Between-study heterogeneity was assessed using Cochran's Q and I(2) statistics. RESULTS: Eight prospective studies (7 publications) with a total of 410,821 subjects and 8284 stroke events were included in the meta-analysis. Overall, a diet containing greater amounts of refined grains was not associated with risk of stroke, with no evidence of heterogeneity among studies (SRR = 1.02; 95% CI, .93-1.10; P(heterogeneity) = .970; I(2) = 0). In addition, no significant associations between consumption of refined grains and risk of stroke were found for both women and men, for both hemorrhagic and ischemic strokes, and for both incident and fatal strokes. These null results are consistent with those of linear dose-response meta-analyses (SRR = .98; 95% CI, .73-1.03 for per 3 servings/day). Consumption of white rice was not associated with risk of stroke (SRR = 1.01; 95% CI, .93-1.11; P(heterogeneity) = .966; I(2) = 0). CONCLUSIONS: The current meta-analysis provides some evidence for the hypothesis that consumption of refined grains was not associated with risk of stroke and its subtypes. PMID- 26365619 TI - The influence of genes on "positive valence systems" constructs: A systematic review. AB - In 2009, the U.S. National Institute of Mental Health (NIMH) proposed an approach toward the deconstruction of psychiatric nosology under the research domain criteria (RDoC) framework. The overarching goal of RDoC is to identify robust, objective measures of behavior, emotion, cognition, and other domains that are more closely related to neurobiology than are diagnoses. A preliminary framework has been constructed, which has connected molecules, genes, brain circuits, behaviors, and other elements to dimensional psychiatric constructs. Although the RDoC framework has salience in emerging studies, foundational literature that pre dated this framework requires synthesis and translation to the evolving objectives and nomenclature of RDoC. Toward this end, we review the candidate gene association, linkage, and genome-wide studies that have implicated a variety of loci and genetic polymorphisms in selected Positive Valence Systems (PVS) constructs. Our goal is to review supporting evidence to currently listed genes implicated in this domain and novel candidates. We systematically searched and reviewed literature based on keywords listed under the June, 2011, edition of the PVS matrix on the RDoC website (http://www.nimh.nih.gov/research priorities/rdoc/positive-valence-systems-workshop-proceedings.shtml), which were supplemented with de novo keywords pertinent to the scope of our review. Several candidate genes linked to the PVS framework were identified from candidate-gene association studies. We also identified novel candidates with loose association to PVS traits from genome-wide studies. There is strong evidence suggesting that PVS constructs, as currently conceptualized under the RDoC initiative, index genetically influenced traits; however, future research, including genetic epidemiological, and psychometric analyses, must be performed. PMID- 26365620 TI - Genetic association of APOA5 and APOE with metabolic syndrome and their interaction with health-related behavior in Korean men. AB - BACKGROUND: Genome-wide association studies have been used extensively to identify genetic variants linked to metabolic syndrome (MetS), but most of them have been conducted in non-Asian populations. This study aimed to evaluate the association between MetS and previously studied single nucleotide polymorphisms (SNPs), and their interaction with health-related behavior in Korean men. METHODS: Seventeen SNPs were genotyped and their association with MetS and its components was tested in 1193 men who enrolled in the study at Seoul National University Hospital. RESULTS: We found that rs662799 near APOA5 and rs769450 in APOE had significant association with MetS and its components. The SNP rs662799 was associated with increased risk of MetS, elevated triglyceride (TG) and low levels of high-density lipoprotein, while rs769450 was associated with a decreased risk of TG. The SNPs showed interactions between alcohol drinking and physical activity, and TG levels in Korean men. CONCLUSIONS: We have identified the genetic association and environmental interaction for MetS in Korean men. These results suggest that a strategy of prevention and treatment should be tailored to personal genotype and the population. PMID- 26365621 TI - Automated contrast medium monitoring system for computed tomography--Intra institutional audit. AB - The aim of this study was to analyze the usage and the data recorded by a RIS PACS-connected contrast medium (CM) monitoring system (Certegra((r)), Bayer Healthcare, Leverkusen, Germany) over 19 months of CT activity. The system used was connected to two dual syringe power injectors (each associated with a 16-row and a high definition 64-row multidetector CT scanner, respectively), allowing to manage contrast medium injection parameters and to send and retrieve CT study related information via RIS/PACS for any scheduled contrast-enhanced CT examination. The system can handle up to 64 variables and can be accessed via touchscreen by CT operators as well as via a web interface by registered users with three different hierarchy levels. Data related to CM injection parameters (i.e. iodine concentration, volume and flow rate of CM, iodine delivery rate and iodine dose, CM injection pressure, and volume and flow rate of saline), patient weight and height, and type of CT study over a testing period spanning from 1 June 2013 to 10 January 2015 were retrieved from the system. Technical alerts occurred for each injection event (such as system disarm due to technical failure, disarm due to operator's stop, incomplete filling of patient data fields, or excessively high injection pressure), as well as interoperability issues related to data sending and receiving to/from the RIS/PACS were also recorded. During the testing period, the CM monitoring system generated a total of 8609 reports, of which 7629 relative to successful injection events (88.6%). 331 alerts were generated, of which 40 resulted in injection interruption and 291 in CM flow rate limitation due to excessively high injection pressure (>325 psi). Average CM volume and flow rate were 93.73 +/- 17.58 mL and 3.53 +/- 0.89 mL/s, and contrast injection pressure ranged between 5 and 167 psi. A statistically significant correlation was found between iodine concentration and peak IDR (rs=0.2744, p<0.0001), as well as between iodine concentration and iodine dose (rs=0.3862, p<0.0001) for all CT studies. Automated contrast management systems can provide a full report of contrast use with the possibility to systematically compare different contrast injection protocols, minimize errors, and optimize organ-specific contrast enhancement for any given patient and clinical application. This can be useful to improve and harmonize the quality and consistency of contrast CT procedures within the same radiological department and across the hospital, as well as to monitor potential adverse events and overall costs. PMID- 26365622 TI - Platelet count and associated morbidities in VLBW infants with pharmacologically treated patent ductus arteriosus. AB - OBJECTIVE: Characterize the diagnosis of PDA and the distribution of pretreatment platelet count in pharmacologically managed PDA in infants <=1500 g and assess the relationship of platelet count to serious morbidities. STUDY DESIGN: This is a retrospective, observational study. In 40 hospitals, data were collected on PDA, including pretreatment platelet count. Distribution of platelet count was examined. The association of platelet count and clinical outcomes of IVH, NEC and PDA closure prior to discharge were examined. Chi-square test was used to compare outcomes by platelet count groups. RESULTS: There were 311 patients treated with medically treated PDA. Pretreatment platelet counts were categorized as 0-119 K, 120-199 K, 200-299 K, >300 K. Incidence and grade of IVH were not significantly different by platelet group. Across all groups: No IVH 62-83%, Grades 1-2 IVH 13 25%, Grades 3-4 IVH 2-13%. NEC occurred in 0-11% of all patients studied. PDA closure rate was 33-45%. CONCLUSION: PDA closure was not significantly affected by platelet count. Platelet count was not a statistically significant factor for development of IVH and NEC in infants born <1500 g with pharmacologically treated PDA. PMID- 26365623 TI - Adam-Gibbs model in the density scaling regime and its implications for the configurational entropy scaling. AB - To solve a long-standing problem of condensed matter physics with determining a proper description of the thermodynamic evolution of the time scale of molecular dynamics near the glass transition, we have extended the well-known Adam-Gibbs model to describe the temperature-volume dependence of structural relaxation times, taualpha(T, V). We also employ the thermodynamic scaling idea reflected in the density scaling power law, taualpha = f(T(-1)V(-gamma)), recently acknowledged as a valid unifying concept in the glass transition physics, to differentiate between physically relevant and irrelevant attempts at formulating the temperature-volume representations of the Adam-Gibbs model. As a consequence, we determine a straightforward relation between the structural relaxation time taualpha and the configurational entropy SC, giving evidence that also SC(T, V) = g(T(-1)V(-gamma)) with the exponent gamma that enables to scale taualpha(T, V). This important findings have meaningful implications for the connection between thermodynamics and molecular dynamics near the glass transition, because it implies that taualpha can be scaled with SC. PMID- 26365624 TI - Seismic evidence of a two-layer lithospheric deformation in the Indian Ocean. AB - Intra-plate deformation and associated earthquakes are enigmatic features on the Earth. The Wharton Basin in the Indian Ocean is one of the most active intra plate deformation zones, confirmed by the occurrence of the 2012 great earthquakes (Mw>=8.2). These earthquakes seem to have ruptured the whole lithosphere, but how this deformation is distributed at depth remains unknown. Here we present seismic reflection images that show faults down to 45 km depth. The amplitude of these reflections in the mantle first decreases with depth down to 25 km and then remains constant down to 45 km. The number of faults imaged along the profile and the number of earthquakes as a function of depth show a similar pattern, suggesting that the lithospheric mantle deformation can be divided into two layers: a highly fractured fluid-filled serpentinized upper layer and a pristine brittle lithospheric mantle where great earthquakes initiate and large stress drops occur. PMID- 26365625 TI - Follow-up of the fate of imazalil from post-harvest lemon surface treatment to a baking experiment. AB - Imazalil is one of the most widespread fungicides used for the post-harvest treatment of citrus species. The separate use of peel during food preparation and processing may hitherto concentrate most of the imazalil into food products, where specific maximum residue limits hardly exist for this fungicide. In order to monitor comprehensively the path of imazalil, our study covered the monitoring of the efficiency of several washing treatments, the comparison of operative and related sample preparation methods for the lemon samples, the validation of a sample preparation technique for a fatty cake matrix, the preparation of a model cake sample made separately either with imazalil containing lemon peel or with imazalil spiking, the monitoring of imazalil degradation into alpha-(2,4 dichlorophenyl)-1H-imidazole-1-ethanol because of the baking process, and finally the mass balance of imazalil throughout the washing experiments and the baking process. Quantification of imazalil was carried out with an LC-ESI-MS/MS set-up, while LC-QTOF was used for the monitoring of imazalil degradation. Concerning the washing, none of the addressed five washing protocols could remove more than 30% of imazalil from the surface of the lemon samples. The study revealed a significant difference between the extraction efficiency of imazalil by the EN 15662:2008 and AOAC 2007.1 methods, with the advantage of the former. The use of the model cake sample helped to validate a modified version of the EN 15662:2008 method that included a freeze-out step to efficiently recover imazalil (>90%) from the fatty cake matrix. The degradation of imazalil during the baking process was significantly higher when this analyte was spiked into the cake matrix than in the case of preparing the cake with imazalil-containing lemon peel (52% vs. 22%). This observation calls the attention to the careful evaluation of pesticide stability data that are based on solution spiking experiments. PMID- 26365626 TI - A Molecular Seesaw Balance: Evaluation of Solvent and Counteranion Effects on Pyridinium-pi Interactions. AB - A molecular seesaw balance 1.MeI has been developed to measure pyridinium-pi interactions. This balance adopts two distinct conformers, A and B, which are stabilized by a cation-pi interaction and a pi-pi interaction, respectively. The conformer ratio was determined on the basis of the averaged (3)J coupling constants for H1-C-C-H2 and the corresponding boundary J values for conformers A and B. The effects of the solvent and the counteranion on the DeltaG values were investigated using this molecular balance. Thermodynamic parameters obtained from a van't Hoff plot helped us to better understand the solvent and counteranion effects. PMID- 26365627 TI - Structure and properties of type-II clathrate Cs8Na16-xTlxGe136. AB - Tl-doped type-II clathrate Cs8Na16-xTlxGe136 was synthesized from its elements. The structure was characterised by single crystal and powder diffraction. Cs8Na16 xTlxGe136 crystallized in the space group Fd3[combining macron]m. The melting point decreased with increasing Tl content at 925.0 degrees C, 922.8 degrees C and 915.7 degrees C for Cs8Na14.76(3)Tl1.24(2)Ge136, Cs8Na9.94(2)Tl6.06(2)Ge136 and Cs8Na8.36(2)Tl7.64(2)Ge136 in Ar atmosphere, respectively. Cs8Na9.94(2)Tl6.06(2)Ge136 exhibited diamagnetism with chi = -3.11 * 10(-3) emu mol(-1) at 1.8 K. The heat capacity of Cs8Na9.94(2)Tl6.06(2)Ge136 presented an Einstein peak at 10 K. The fitted parameters for Cs8Na9.94(2)Tl6.06(2)Ge136 were lambda = 0.115(4) J mol(-1) K(-2), beta = 0.0289(2) J mol(-1) K(-4), NE = 7.94(4), thetaE = 56.9(1) K, ND = 152.06(4) and thetaD = 217(1) K using the equation Cp = Ce + CD + CE from 1.8 K to 10 K. The thermoelectric measurement showed metallic resistivity and a negative Seebeck coefficient, indicating electron-type charge carriers. The electronic structure calculation for Cs8Na10Tl6Ge136 confirmed the nature of the metallic transport behavior with conducting electrons, mainly from the Ge p orbitals. PMID- 26365628 TI - Saccharomyces cerevisiae as a model in ecotoxicological studies: A post-genomics perspective. AB - The budding yeast Saccharomyces cerevisiae represents a well-consolidated and widely used eukaryotic model, with a number of features that make it an ideal organism to carry out functional toxicological studies. Several advantages are permitted by the use of yeast cells, as the possibility to identify molecular biomarkers, unknown mechanisms of action and novel potential targets. Thanks to the evolutionary conservation, yeast can provide also useful clues allowing the prioritization of more complex analyses and toxicity predictions in higher eukaryotes. The last two decades were incredibly fruitful for yeast "omics", but referring to the analysis of the effects of pesticides on yeast much still remains to be done. Furthermore, a deeper knowledge of the effects of environmental pollutants on biotechnological processes associated with the use of yeasts is to be hoped. PMID- 26365629 TI - Low temperature deposition of 2D WS2 layers from WF6 and H2S precursors: impact of reducing agents. AB - We demonstrate the impact of reducing agents for Chemical Vapor Deposition (CVD) and Atomic Layer Deposition (ALD) of WS2 from WF6 and H2S precursors. Nanocrystalline WS2 layers with a two-dimensional structure can be obtained at low deposition temperatures (300-450 degrees C) without using a template or anneal. PMID- 26365630 TI - Vitamin therapy after heart transplantation. AB - The need for routine nutritional supplementation with vitamins in most healthy individuals remains a matter of debate and current guidelines recommend that the need for these essential nutrients be met primarily through consuming an adequate diet. However, after heart transplantation, multiple factors, including the effects of prolonged debilitation prior to surgery and immunosuppression, may lead to physiological stress, which may justify consideration for vitamin supplementation. In general, clinical trials have not focused on vitamin supplementation after heart transplantation. There appears to be some limited clinical data to support the use of certain vitamins after heart transplantation. In particular, the putative antioxidant properties of vitamins C and E after heart transplantation may be beneficial as prophylaxis against cardiac allograft vasculopathy, and vitamin D, in conjunction with calcium, may help prevent post transplant bone loss. Current guidelines only address the use of vitamin D after heart transplantation. PMID- 26365631 TI - Fyn Accelerates M Phase Progression by Promoting the Assembly of Mitotic Spindle Microtubules. AB - The mitotic spindle is the major piece of cellular machinery essential for faithful chromosome segregation. Whereas Fyn, a member of Src-family kinases, is known to be localized to the meiotic and mitotic spindle microtubules, the role of Fyn in mitotic spindle formation has not yet been completely elucidated. In this study, we studied the role of Fyn in spindle formation and effects on M phase progression. Re-expression of Fyn induced increases in the fluorescence intensity of mitotic spindle microtubules in SYF cells having triple knock-out mutations of c-Src, c-Yes, and Fyn. Cold treatment results showed that Fyn increases the maximum length of microtubules in HeLa S3 cells in a manner dependent on Fyn kinase activity. Complete depolymerization of microtubules under cold treatment and the following release into 37 degrees C revealed that the increase in the microtubule length in Fyn-expressing cells may be attributed to the promotion of microtubule polymerization. After cold treatment, Fyn promotes the accumulation of EB1, which is a plus-end tracking protein and facilitates microtubule growth, in a manner dependent on the kinase activity. Furthermore, Fyn accelerates the M phase progression of cells from nocodazole arrest. These results suggest that Fyn facilitates mitotic spindle formation through the increase in microtubule polymerization, resulting in the acceleration of M-phase progression. PMID- 26365632 TI - Carbon-nitrogen bond construction and carbon-oxygen double bond cleavage on a molecular titanium oxonitride: a combined experimental and computational study. AB - New carbon-nitrogen bonds were formed on addition of isocyanide and ketone reagents to the oxonitride species [{Ti(eta(5)-C5Me5)(MU-O)}3(MU3-N)] (1). Reaction of 1 with XylNC (Xyl = 2,6-Me2C6H3) in a 1:3 molar ratio at room temperature leads to compound [{Ti(eta(5)-C5Me5)(MU-O)}3(MU-XylNCCNXyl)(NCNXyl)] (2), after the addition of the nitrido group to one coordinated isocyanide and the carbon-carbon coupling of the other two isocyanide molecules have taken place. Thermolysis of 2 gives [{Ti(eta(5)-C5Me5)(MU-O)}3(XylNCNXyl)(CN)] (3) where the heterocumulene [XylNCCNXyl] moiety and the carbodiimido [NCNXyl] fragment in 2 have undergone net transformations. Similarly, tert-butyl isocyanide (tBuNC) reacts with the starting material 1 under mild conditions to give the paramagnetic derivative [{Ti3(eta(5)-C5Me5)3(MU-O)3(NCNtBu)}2(MU-CN)2] (4). However, compound 1 provides the oxo ketimide derivatives [{Ti3(eta(5) C5Me5)3(MU-O)4}(NCRPh)] [R = Ph (5), p-Me(C6H4) (6), o-Me(C6H4) (7)] upon reaction with benzophenone, p-methylbenzophenone, and o-methylbenzophenone, respectively. In these reactions, the carbon-oxygen double bond is completely ruptured, leading to the formation of a carbon-nitrogen and two metal-oxygen bonds. The molecular structures of complexes 2-4, 6, and 7 were determined by single-crystal X-ray diffraction analyses. Density functional theory calculations were performed on the incorporation of isocyanides and ketones to the model complex [{Ti(eta(5)-C5H5)(MU-O)}3(MU3-N)] (1H). The mechanism involves the coordination of the substrates to one of the titanium metal centers, followed by an isomerization to place those substrates cis with respect to the apical nitrogen of 1H, where carbon-nitrogen bond formation occurs with a low-energy barrier. In the case of aryl isocyanides, the resulting complex incorporates additional isocyanide molecules leading to a carbon-carbon coupling. With ketones, the high oxophilicity of titanium promotes the unusual total cleavage of the carbon-oxygen double bond. PMID- 26365633 TI - Lack of association between RAD50-IL13 polymorphisms and pediatric asthma susceptibility in Northeastern Han Chinese. AB - OBJECTIVE: RAD50-IL13 region has been recently identified as one of critical asthma susceptibility loci in genome-wide association studies, yet the role of these genetic variants or single-nucleotide polymorphisms (SNPs) in the risk of developing asthma in Northeastern Han Chinese remains largely unknown. METHODS: We conducted an association study by genotyping four SNPs (rs2244012 and rs6871536 in RAD50 as well as rs1295686 and rs1800925 in IL13) in 652 asthmatic children and age-matched 752 healthy controls from Northeastern Han Chinese to evaluate the asthma susceptibility with each individual SNP using SNaPshot genotyping method. RESULTS: We did not find the allele or genotype frequency distribution of four SNPs in RAD50-IL13 region which was significantly different between asthmatic children and controls (p > 0.05). CONCLUSIONS: Our findings first suggested that the variants in RAD50-IL13 region were not associated with asthma risk in Northeastern Han Chinese children. PMID- 26365634 TI - [Honoring caregivers]. PMID- 26365635 TI - [Nursing care of the coma patient]. PMID- 26365636 TI - [Coma in France today]. AB - Comas result from acute life-threatening neurological failure. To understand coma, it is firstly necessary to define it, to cite the aetiologies and their epidemiology and to describe the chronic disorders of consciousness. It is also important to address the challenges and principles of treatment during the acute phase. PMID- 26365638 TI - [Coma and communication]. AB - Communication around a comatose patient is a touchy subject. In the event of a breakdown in this interaction, there is a risk of a strained relationship being established between the nurses, the patient and their family, a source of conflicts or value judge ments. The objective of appropriate communication is to place the patient back at the centre of the relationship. PMID- 26365637 TI - [Ethics and coma]. AB - Advances in intensive care enable certain comatose patients to be kept alive, with the risk of them developing serious neurological sequelae. Ethical problems are therefore raised in the acute stage, with questions relating to the continuation of complex intensive care in a non-autonomous patient whose neurological condition remains unstable. The accuracy of the prognosis during the care may give rise to the possibility, in the event of an unfavourable evolution, of limiting or stopping treatments. This decision must take into account the family, be discussed collectively and assumed by the whole nursing team. PMID- 26365639 TI - [The organization of a post-intensive care rehabilitation unit]. AB - When a patient is admitted to a post-intensive care rehabilitation unit, the functional outcome is the main objective of the care. The motivation of the team relies on strong cohesion between professionals. Personalised support provides a heightened observation of the patient's progress. Listening and sharing favour a relationship of trust between the patient, the team and the families. PMID- 26365641 TI - [When all hope has gone...well-placed affection remains]. AB - Cedric de Linage experienced coma through his wife, Amelie, after she suffered cardiopulmonary arrest. Here he describes the crucial role, during this period of uncertainty and fear, played by the nursing team. Through their care and day-to day compassion, the team was able to treat the patient as a fragile but living patient. PMID- 26365640 TI - [The coma awakening unit, between intensive care and rehabilitation]. AB - After intensive care and before classic neurological rehabilitation is possible, patients in an altered state of consciousness are cared for at early stages in so called coma awakening units. The care involves, on the one hand, the complex support of the patient's awakening from coma as a neurological and existential process, and on the other, support for their families. PMID- 26365642 TI - [Nursing tutor, working closely with students]. AB - Appreciating the chance to work independently as well as interacting with the different nursing teams in her hospital, a nursing tutor tells us of the pleasure she gets out of dedicating herself to supporting student nurses. A way of approaching care from a different perspective. PMID- 26365643 TI - [Connectivity and care, innovative tools for the benefit of patients]. AB - The first department within Clermont-Ferrand university hospital to have undergone the introduction of electronic patient records, the pulmonology department again served as the pilot for studying connectivity solutions. Time savings, increased use of the electronic patient records and improved quality of care are the outcomes highlighted by a survey of the nurses in this unit. PMID- 26365644 TI - [Nurses engaged in the fight against leprosy]. AB - Even now in the 21st century, leprosy is still rife, notably among poor populations. In the regions of the world concerned, nurses specialised in the disease play an essential role in supporting the screening, treatment and reintegration of patients. In more than twenty countries, the Order of Malta France is acting to fight against leprosy. PMID- 26365645 TI - [Nurse telephone support at home during chemotherapy]. AB - An innovative scheme has been operational since 2013 at the Institut Claudius Regaud in Toulouse, aimed at patients undergoing chemotherapy. After an initial consultation, patients receive regular telephone support at home from expert nurses between treatments. The scheme helps to improve patient management and reinforce the community-hospital link. PMID- 26365646 TI - [Assessing the experience of practice placement nurse tutors]. AB - Focused for many years on the quality of the supervision of student nurses during their practice placements, the teams of the American Hospital of Paris carried out an original survey around the new nurse training reference framework, questioning nurse tutors and young frontline professionals. PMID- 26365647 TI - [Gestational diabetes]. PMID- 26365648 TI - Dealing with Scabies in a Hospital Ward. AB - A case of scabies has been diagnosed in the Medical Ward where Sophie works, and the hospital is having to take appropriate measures. Scabies mites can spread quickly, and staff who are in contact with the infected patient risk catching the parasites and contaminating their own family in turn. One of the night nurses is probably infected. PMID- 26365649 TI - [Nursing management of pain]. PMID- 26365650 TI - [Students of different health disciplines sharing their knowledge]. PMID- 26365651 TI - [Examining the hair and scalp for fungal diseases]. PMID- 26365652 TI - Estimation of instantaneous venous blood saturation using the photoplethysmograph waveform. AB - Non-invasive estimation of regional venous saturation (SxvO2) using a conventional pulse oximeter could provide a means of obtaining clinically relevant information. This study was carried out in order to investigate the hypothesis that SxvO2 could be estimated by utilising the modulations created by positive pressure ventilation in the photoplethysmograph (PPG) signals. The modulations caused by the mechanical ventilator were extracted from oesophageal PPG signals obtained from 12 patients undergoing cardiothoracic surgery. The signals analysed in this work were acquired in a previous study. For the purpose of this analysis the raw PPG signal was considered to have three major components, ac PPG signal (cardiac related component), a static component or dc PPG signal (created mostly by the absorption of light by surrounding tissue) and the ventilator modulation component. These components were then used to estimate instantaneous arterial blood oxygen saturation (SpO2) and SxvO2 by utilising time frequency analysis technique of smoothed-pseudo Wigner-Ville distribution (SPWVD). The results showed that there was no significant difference in the traditionally-derived (time-domain) arterial saturation and the instantaneous arterial saturation. However, the instantaneous venous saturation was found to be significantly lower than the estimated time-domain and instantaneous arterial saturation (P = < 0.001, n = 12). PMID- 26365653 TI - Phenotypes of comorbidity in OSAS patients: combining categorical principal component analysis with cluster analysis. AB - Phenotyping obstructive sleep apnea syndrome's comorbidity has been attempted for the first time only recently. The aim of our study was to determine phenotypes of comorbidity in obstructive sleep apnea syndrome patients employing a data-driven approach. Data from 1472 consecutive patient records were recovered from our hospital's database. Categorical principal component analysis and two-step clustering were employed to detect distinct clusters in the data. Univariate comparisons between clusters included one-way analysis of variance with Bonferroni correction and chi-square tests. Predictors of pairwise cluster membership were determined via a binary logistic regression model. The analyses revealed six distinct clusters: A, 'healthy, reporting sleeping related symptoms'; B, 'mild obstructive sleep apnea syndrome without significant comorbidities'; C1: 'moderate obstructive sleep apnea syndrome, obesity, without significant comorbidities'; C2: 'moderate obstructive sleep apnea syndrome with severe comorbidity, obesity and the exclusive inclusion of stroke'; D1: 'severe obstructive sleep apnea syndrome and obesity without comorbidity and a 33.8% prevalence of hypertension'; and D2: 'severe obstructive sleep apnea syndrome with severe comorbidities, along with the highest Epworth Sleepiness Scale score and highest body mass index'. Clusters differed significantly in apnea-hypopnea index, oxygen desaturation index; arousal index; age, body mass index, minimum oxygen saturation and daytime oxygen saturation (one-way analysis of variance P < 0.0001). Binary logistic regression indicated that older age, greater body mass index, lower daytime oxygen saturation and hypertension were associated independently with an increased risk of belonging in a comorbid cluster. Six distinct phenotypes of obstructive sleep apnea syndrome and its comorbidities were identified. Mapping the heterogeneity of the obstructive sleep apnea syndrome may help the early identification of at-risk groups. Finally, determining predictors of comorbidity for the moderate and severe strata of these phenotypes implies a need to take these factors into account when considering obstructive sleep apnea syndrome treatment options. PMID- 26365654 TI - Fetal thymus: visualization rate and volume by integrating 2D- and 3D-ultrasound during 2nd trimester echocardiography. AB - OBJECTIVE: To assess the visualization rate and transverse diameter of fetal thymus by two-dimensional ultrasound (2DUS) as well as the fetal thymus volume by three-dimensional ultrasound (3DUS) during the 2nd trimester echocardiography. METHODS: A prospective cross-sectional study involving 100 normal fetuses between 18w0d and 23w6d was performed. The identification of fetal thymus and peri-thymic vessels was realized at level of three vessels and trachea (3VT). The transverse diameter was obtained placing a line cursor perpendicular to the line connecting the sternum and the spine. The fetal thymus volume was obtained by virtual organ computer-aided analysis (VOCAL) with 30 degrees of rotation. We used the percentage of visualization rate of 2D structures and means and 95% confidence intervals (CI) for fetal thymus transverse diameter and volume. RESULTS: The visualization rate of fetal thymus by 2DUS was of 100% in all gestational ages using the 3VT view. Addition of color Doppler ultrasound facilitates identification of the thy-box and enhanced the calculation of both fetal thymus transverse diameter and volume. The mean fetal thymus transverse diameter by 2DUS ranged from 11 mm at 18 weeks to 19 mm at 23 weeks of gestation. The mean fetal thymus volume by 3DUS ranged from 1.25 cm(3) at 18 weeks to 2.61 cm(3) at 23 weeks of gestation. CONCLUSION: We demonstrated a high visualization rate of fetal thymus and peri-thymic vessels by 2DUS during the 2nd trimester echocardiography. The measurements of transverse diameter by 2DUS and the volume by 3DUS also showed a high success rate. PMID- 26365655 TI - The effect of trainee involvement on perioperative outcomes of abdominal aortic aneurysm repair. AB - OBJECTIVE: Although the effect of trainee involvement has been evaluated across different specialties, their effects on perioperative outcomes after abdominal aortic aneurysm (AAA) repair have not been examined. Our goal was to examine the association between resident and fellow intraoperative participation with perioperative outcomes of endovascular AAA repair (EVAR), open infrarenal AAA repair (OIAR), and open juxtarenal AAA repair (OJAR). METHODS: The American College of Surgeons National Surgical Quality Improvement Program data set (2005 2012) was queried to identify all patients who underwent EVAR, OIAR, or OJAR. Multivariate analysis was performed to assess the association of trainee involvement with perioperative morbidity and mortality. RESULTS: We identified 16,977 patients: 12,003 with EVAR, 3655 with OIAR, and 1319 with OJAR. Propensity matching and multivariate analyses revealed that there was no significant difference in perioperative death, cardiac arrest/myocardial infarction, pulmonary, renal, venous thromboembolic, or wound complications, or return to the operating room. However, trainee involvement in AAA repair led to a significant increase in operative time for EVAR (163 +/- 77 vs 140 +/- 67 minutes; P < .001), OIAR (217 +/- 91 vs 185 +/- 76 minutes; P < .001), and OJAR (267 +/- 115 vs 214 +/- 106 minutes; P < .001) and an extended length of stay for EVAR (3.1 +/- 5.3 vs 2.8 +/- 4.5 days; P < .001) and OIAR (10.6 +/- 11.8 vs 9.1 +/- 8.9 days; P < .001). CONCLUSIONS: Trainee participation in aneurysm repair was not associated with major adverse perioperative outcomes. However, it was associated with an increased operative time and length of stay and therefore may lead to increased resource utilization and cost. PMID- 26365656 TI - Thoracic aortic strain can affect endograft sizing in young patients. AB - OBJECTIVE: Aortic computed tomography angiography (CTA) examination with electrocardiography gating is becoming the clinical routine image acquisition protocol for diagnosis and intervention planning. To minimize motion artifact, the images are reconstructed in the diastolic phase of the cardiac cycle. The aim of our study was to quantify aortic strain in an elderly nonaneurysmatic patient cohort and to identify the phases of the R-R cycle that correspond to the minimal and maximal aortic diameters. The quantification of aortic strain may enable the improvement of intervention planning and the introduction of more effective dose saving protocols for CTA scans. METHODS: We assessed CTA images of 28 patients (14 men; mean age, 74 years). Aortic calcium score was calculated on native images. Angiography images were reconstructed in equally spaced 10 phases of the R-R cycle. After semiautomatic centerline analysis, we measured the cross sectional areas in each of the 10 phases at 9 specific segments between the ascending aorta and the common iliac bifurcation representing the attachment sites of thoracic and abdominal stent grafts. Area-derived effective diameter, pulsatility (Amax - Amin), and strain [(Amax - Amin)/Amin] were calculated. Repeated measurements were taken to evaluate inter-reader and intrareader reproducibility (10-10 patients each). RESULTS: A total of 4320 measurements were performed. We found significant difference between diastolic and systolic diameters (DD,Z0 = 33.2, DS,Z0 = 34.4; P < .001). Pulsatility values of the vessel diameters were 1.0 to 1.1 mm in the thoracic aorta, 0.7 to 0.9 mm in the abdominal aorta, and 0.5 to 0.6 mm in the common iliac arteries. Negative, moderate correlations were found between aortic strain and age (r = -0.586; P = .001), aortic strain and plaque area (r = -0.429; P = .026), and age and body mass index (r = -0.412; P = .029). We found positive, moderate correlation between age and plaque area (r = 0.594; P = .001). The aortic pulsatility curve has a positive extreme at 30% and a negative extreme at 90% of the R-R cycle throughout the aorta. Lin concordance coefficients were 0.987 for inter-reader and 0.994 for intrareader correlations. CONCLUSIONS: Aortic strain can be reliably quantified on electrocardiography-gated CTA images. Pulsatility of the aorta can be substantial in the thoracic aortic segments of young patients; therefore, the routine use of systolic images is not recommended. In addition, we demonstrated that images at 30% of the heart cycle correspond to the largest diameter of the aorta. PMID- 26365657 TI - Discussion. PMID- 26365658 TI - Increased reintervention in radial-cephalic arteriovenous fistulas with anastomotic angles of less than 30 degrees. AB - OBJECTIVE: Although radial-cephalic (RC) and brachial-cephalic (BC) fistulas are the recommended primary accesses for hemodialysis, access failure is frequently due to juxta-anastomotic stenosis (JAS). Because increased turbulence at the anastomosis may lead to JAS, we hypothesized that an acute angle at the arteriovenous anastomosis is associated with JAS, reduced fistula patency, and increased reinterventions. METHODS: Between February 2013 and September 2014, the anastomotic angle and vessel diameters were prospectively collected for all patients who underwent RC or BC fistula creation. The primary end point was reintervention on the juxta-anastomotic segment. Secondary end points were primary and secondary patency of the fistula. RESULTS: A total of 149 patients (median age, 72 years) received 73 RC and 76 BC fistulas; the median follow-up was 7 months (range, 1-22 months) for RC and 12 months (range, 2-24 months) for BC fistulas. The median anastomotic angle in RC fistulas, was 30 degrees . Anastomotic angles of <30 degrees were associated with reduced primary patency (38% vs 66%, P = .003) and secondary patency (84% vs 97%, P = .02) and increased numbers of reinterventions (67% vs 34%, P = .001). Cox analysis showed that an anastomotic angle of <30 degrees was an independent factor predicting decreased primary patency (P = .009) and secondary patency (P = .03) as well as increased reinterventions (P = .004). In BC fistulas, the median anastomotic angle was 90 degrees . Patients with anastomotic angles <90 degrees and >=90 degrees had similar rates of primary patency (67% vs 67%, P = .39) and secondary patency (93% vs 94%, P = .89) at 6 months, with a similar reintervention rate at 12 months (31% vs 32%, P = .56). Vein diameter was the only factor that predicted reintervention (P < .0001). CONCLUSIONS: RC fistulas with anastomotic angles of <30 degrees have reduced primary and secondary patency and increased numbers of reinterventions, suggesting that, if possible, surgeons should avoid an anastomotic angle of <30 degrees when creating RC fistulas. Anastomotic angles of <90 degrees or >=90 degrees may not play a role in outcome of BC fistulas. PMID- 26365659 TI - Geographic disparities in the burden of ruptured and unruptured abdominal aortic aneurysms. AB - BACKGROUND: The province of Saskatchewan presents unique challenges for the care of ruptured abdominal aortic aneurysms (AAAs), including variable access to health care resources and long transportation distances to tertiary vascular care. This study assessed the rates of ruptured and total AAA to determine regional variations within Saskatchewan and ascertain whether there are areas of high AAA prevalence that would possibly benefit from the implementation of a targeted screening program. METHODS: All diagnoses of AAA from 2001 to 2012 in the province of Saskatchewan were reviewed, with patients grouped by health region of residence. Diagnoses of ruptured and unruptured AAAs were obtained from the Saskatchewan Discharge Abstracts Database, Medical Services Billings Claims data, and Vital Statistics data. RESULTS: During the study period, 6163 AAAs were diagnosed. The provincial age-adjusted rate of AAA was 53.0/100,000 person-years (95% confidence interval, 48.8-57.6). The highest age-adjusted rate of AAA was found in the Five Hills Health Region (FHHR), at 63.1/100,000 person-years (95% confidence interval, 57.6-69.0), which was significantly higher than the provincial average (P < .05). The rate of ruptured AAA in FHHR was nearly twofold higher than the provincial average (6.0 vs 2.9/100,000 person-years, respectively). CONCLUSIONS: There are significant geographic variations in the prevalence of AAA in the province of Saskatchewan, with the highest rate of AAA found in the FHHR. PMID- 26365660 TI - The correlation between computed tomography and duplex evaluation of autogenous vein bypass grafts and their relationship to failure. AB - OBJECTIVE: Duplex ultrasound (DUS) imaging for vein bypass graft (VBG) surveillance is confounded by technical and physiologic factors that reduce the sensitivity for detecting impending graft failure. In contrast, three-dimensional computed tomography angiography (CTA) offers high-fidelity anatomic characterization of VBGs, but its utility in detecting at risk grafts is unknown. The current study analyzed the correlation between DUS and CTA for detection of vein graft stenosis and evaluated the relationship of the observed abnormalities to VBG failure. METHODS: Consecutive lower extremity VBG patients underwent surveillance with concurrent DUS imaging and CTA at 1 week and at 1, 6, and 12 months postoperatively. A standardized algorithm was used for CT reconstruction and extraction of the lumen geometries at 1-mm intervals. At each interval, CT derived cross-sectional areas were coregistered and correlated to DUS peak systolic velocities (PSVs) within six predesignated anatomic zones and then analyzed for outcome association. Vein graft failure was defined as pathologic change within a given anatomic zone resulting in thrombosis, amputation, or reintervention within the 6-month period after the observed time point. RESULTS: The study recruited 54 patients, and 10 (18%) experienced failure <=18 months of implantation. The expected inverse relationship between cross-sectional area and PSV was only weakly correlated (Spearman rank coefficient = -0.19). Moderate elevations in the PSV ratio (PSVr; 2-3.5) were frequently transient, with 14 of 18 grafts (78%) demonstrating ratio reduction on subsequent imaging. A PSVr >=3.5 was associated with a 67% failure rate. CT stenosis <50% was highly correlated with success (0 failures); however, high-grade (>80%) CT stenosis was more likely to succeed than to fail (25%). Significant discordance between CT and DUS was found in 18 patients. Although 14 of these patients had CT stenosis >70% with a PSVr <3.5, subsequent failure occurred in only two. Conversely, graft failure occurred in three of four patients with CT stenosis <70% but PSVr >3.5. Focused analysis of these patients using computational fluid dynamic modeling demonstrated that vein side branches, local tortuosity, regional diameter variations, and venovenostomies were the drivers of these discrepancies. CONCLUSIONS: This analysis demonstrated that a PSVr >=3.5 is strongly correlated with VBG failure, whereas the natural history of moderately elevated PSVr (2-3.5) is largely clinically benign. Although minimum stenosis on the CT scan was highly predictive of success, high-grade CT stenosis was infrequently associated with failure. The interaction of anatomic features with the local flow dynamics was identified as the primary confounder for a direct correlation between CT and DUS imaging. PMID- 26365661 TI - Spinal cord ischemia after endovascular repair of thoracoabdominal aortic aneurysms with fenestrated and branched stent grafts. AB - OBJECTIVE: The aim of this study was to report the incidence and associated risk factors of perioperative spinal cord ischemia (SCI) after endovascular repair of thoracoabdominal aortic aneurysms (TAAAs) with fenestrated and branched stent grafts. METHODS: The study included consecutive patients with TAAA treated with fenestrated and branched stent grafts within the period January 2004 to December 2014. Suprarenal abdominal aortic aneurysms treated with fenestrated and branched grafts, even if including all four visceral vessels, were excluded. Patients who died within 30 days after the procedure were excluded from the analysis for SCI. All data were collected prospectively. RESULTS: A total of 218 patients (167 men; mean age, 68.8 +/- 7.5 years) were treated. Thirty-day mortality was 17 patients (7.8%). TAAA distribution among the 201 surviving patients was as follows: type I, n = 17 (8.5%); type II, n = 55 (27.4%); type III, n = 63 (31.3%); type IV, n = 54 (26.9%); and type V, n = 12 (5.9%). In the surviving patients, 21 (10.4%) developed perioperative SCI. At 30 days postoperatively, 13 (6.5%) of those patients had transient lower limb weakness, 5 patients (2.5%) had persistent lower limb weakness requiring assistance to stand or to walk, and 3 patients (1.5%) had persistent paraplegia. Five of the 21 patients awoke from anesthesia with a neurologic deficit. The remaining 16 patients had a later postoperative onset of SCI, with the majority of them (14 of 16) within 72 hours after the operation. Multivariate analysis using logistic regression identified operation time >300 minutes (odds ratio [OR], 7.4; 95% confidence interval [CI], 2.6-21.1; P < .001), peripheral arterial disease (OR, 6.6; 95% CI, 2-21.9; P = .002), and baseline renal insufficiency (glomerular filtration rate <30 mL/min; OR, 4.1; 95% CI, 1.1-16.1; P = .04) as independent risk factors for SCI. CONCLUSIONS: In our experience, most SCI events after endovascular TAAA repair are transient, with persistent paraplegia being rare. Patients with prolonged procedure duration, peripheral arterial disease, and baseline renal insufficiency appear to be at higher risk for development of SCI after endovascular TAAA repair. PMID- 26365662 TI - Intraspinal collateral circulation to the artery of Adamkiewicz detected with intra-arterial injected computed tomographic angiography. AB - When the intercostal and lumbar arteries are occluded by plaque or thrombus, spinal cord perfusion depends on collateral circulation. Some reports have demonstrated collateral circulation to the artery of Adamkiewicz via computed tomography and magnetic resonance angiographies. However, intraspinal collateral circulation to the artery of Adamkiewicz along the spinal cord has not been reported previously. Here, we report two patients with intraspinal collateral circulation to the artery of Adamkiewicz along the spinal cord that was detected with intra-arterial injected computed tomography angiography. PMID- 26365663 TI - Clinical outcomes of thoracic endovascular aneurysm repair using commercially available fenestrated stent graft (Najuta endograft). AB - OBJECTIVE: Thoracic endovascular aneurysm repair (TEVAR) for the aortic arch aneurysm is challenging because of its curved anatomic configuration and the presence of the supra-aortic branches. The Najuta fenestrated endograft (Kawasumi Laboratories, Inc, Tokyo, Japan) was developed to treat aortic arch diseases, offering maximal proximal landing length while preserving the blood flow to the supra-aortic branches. We evaluated the perioperative and midterm outcomes of this fenestrated endograft. METHODS: Between July 2007 and July 2013, 32 patients were treated with the Najuta endograft at three vascular centers. The mean age of the patients was 74.5 +/- 9.8 years (23 patients were men). Technical success, complication, overall survival rate, freedom from aneurysm-related death, secondary intervention, aneurysm enlargement, device migration, and patency of supra-aortic branches were investigated retrospectively. RESULTS: The median follow-up period was 2.5 years (range, 0.2-6.2 years). Seventy-one supra-aortic vessels (30 brachiocephalic arteries, 31 left common carotid arteries, 10 left subclavian arteries) were planned to be preserved with fenestrations. Technical success rate was 91% (29 of 32; three type I endoleaks were seen), and five perioperative complications (two Stanford A dissections, one cerebral infarction, one celiac artery obstruction, one spinal cord ischemia) were recognized. Perioperative death was not observed. Overall survival rate and rate of freedom from aneurysm-related death at 3 years were 67% and 97%, respectively. The rate of freedom from secondary intervention and the rate of freedom from aneurysm enlargement at 3 years were 84% and 85%, respectively. Device migration was not observed. There were two branch (left carotid artery and left subclavian artery) occlusions at 2 weeks after TEVAR due to the endograft's infolding. No other branch occlusion was seen in this follow-up period. As a result, the patency rate of the supra-aortic branch was 97% at 3 years. CONCLUSIONS: The perioperative and 3-year outcomes of TEVAR using the Najuta precurved, fenestrated endograft demonstrated high freedom from aneurysm enlargement and patency rates of the supra-aortic branches. PMID- 26365664 TI - Feasibility of endovascular repair of splenic artery aneurysms using stent grafts. AB - OBJECTIVE: Percutaneous transcatheter embolization of splenic artery aneurysms (SAAs) has been widely accepted as the first line of treatment in patients with symptoms, rupture, or large aneurysm size. Although embolization can usually be performed safely, ischemic complications, such as splenic infarct or abscess, occur in some patients. This study evaluated the feasibility and outcomes of endovascular SAA repair (ESAAR) using stent grafts, which may allow treatment while preserving flow to the spleen. METHODS: We reviewed the clinical data of all consecutive patients who underwent ESAAR using stent grafts. Brachial access was used except for patients with favorable angle of origin from the aorta. To overcome tortuosity and provide support, a coaxial system with a hydrophilic sheath was used. Low-profile 0.018-inch stent grafts were used for distal SAAs with a 10-mm to 15-mm length of proximal and distal segment of splenic artery measuring 4 to 11 mm in diameter. Follow-up included clinical examination and computed tomography imaging within 4 to 6 months after the procedure and yearly thereafter. End points were morbidity, stent graft patency, and freedom from endoleaks and reinterventions. RESULTS: ESAAR was attempted in 10 patients, four males and six females, with median age of 64 years (range, 48-77 years). Median SAA size was 2.8 cm (range, 2-5.7 cm). Nine patients were asymptomatic, and one had pancreatitis and gastrointestinal bleeding. The arterial access site was the brachial artery in six patients and the femoral artery in four. Two patients had brachial and femoral access to facilitate splenic artery stenting. Technical success of ESAAR using stent grafts was 80% (8 of 10). In two patients with distal SAAs, stent graft placement was not possible due to excessive vessel tortuosity, and treatment was by coil embolization. One patient developed brachial artery thrombosis, which was treated surgically. There were no ischemic complications in patients treated by ESAAR with stent grafts. Median length of stay was 1 day. One patient treated by coil embolization developed splenic infarct, which required readmission for pain control. Median follow-up was 9 months. Follow-up imaging in all successfully stented patients revealed patent stent grafts, no endoleak, and no aneurysm sac enlargement. No reinterventions were required. CONCLUSIONS: ESAAR using self-expandable stent grafts offers a viable alternative to coil embolization in selected patients with SAAs. Distal SAAs with excessive vessel tortuosity may result in technical failure requiring embolization. Among patients who underwent successful ESAAR, there were no ischemic complications, stent graft occlusions, endoleaks, or sac enlargement. PMID- 26365665 TI - Vascular complications and surgical interventions after world's largest Q fever outbreak. AB - OBJECTIVE: Since chronic Q fever often develops insidiously, and symptoms are not always recognized at an early stage, complications are often present at the time of diagnosis. We describe complications associated with vascular chronic Q fever as found in the largest cohort of chronic Q fever patients so far. METHODS: Patients with proven or probable chronic Q fever with a focus of infection in an aortic aneurysm or vascular graft were included in this study, using the Dutch national chronic Q fever database. RESULTS: A total of 122 patients were diagnosed with vascular chronic Q fever between April 2008 and June 2012. The infection affected a vascular graft in 62 patients (50.8%) and an aneurysm in 53 patients (43.7%). Seven patients (5.7%) had a different vascular focus. Thirty six patients (29.5%) presented with acute complications, and 35 of these patients (97.2%) underwent surgery. Following diagnosis and start of antibiotic treatment, 26 patients (21.3%) presented with a variety of complications requiring surgical treatment during a mean follow-up of 14.1 +/- 9.1 months. The overall mortality rate was 23.7%. Among these patients, mortality was associated with chronic Q fever in 18 patients (62.1%). CONCLUSIONS: The management of vascular infections with C. burnetii tends to be complicated. Diagnosis is often difficult due to asymptomatic presentation. Patients undergo challenging surgical corrections and long-term antibiotic treatment. Complication rates and mortality are high in this patient cohort. PMID- 26365666 TI - Blood parasites in northern goshawk (Accipiter gentilis) with an emphasis to Leucocytozoon toddi. AB - Haemosporidians and trypanosomes of the northern goshawk (Accipiter gentilis) population in the Czech Republic were studied by morphological and molecular methods. Despite the wide distribution of these medium-large birds of prey, virtually nothing is known about their blood parasites. During a 5-year period, altogether 88 nestlings and 15 adults were screened for haemosporidians and trypanosomes by microscopic examination of blood smears and by nested PCR. Both methods revealed consistently higher prevalence of blood protists in adults, Leucocytozoon (80.0 % in adults vs. 13.6 % in nestlings), Haemoproteus (60.0 vs. 2.3 %), Plasmodium (6.7 vs. 0 %), and Trypanosoma (60.0 vs. 2.3 %). Altogether, five haemosporidian lineages were detected by cytochrome b sequencing. Two broadly distributed and host nonspecific lineages, Plasmodium (TURDUS1) and Leucocytozoon (BT2), were detected only sporadically, while three newly described northern goshawk host-specific Leucocytozoon lineages (ACGE01-03) represent the absolute majority of the haemosporidians identified by molecular methods. Our findings support evidences that in falconiform birds the Leucocytozoon toddi group is formed by several host-specific clusters, with Leucocytozoon buteonis in buzzards and Leucocytozoon mathisi in hawks. Between-year comparisons revealed that the infection status of adults remained predominantly unchanged and individuals stayed uninfected or possessed the same parasite lineages; however, two gains and one loss of blood parasite taxa were also recorded. PMID- 26365667 TI - Haemosporidian infections in the Tengmalm's Owl (Aegolius funereus) and potential insect vectors of their transmission. AB - Sedentary bird species are suitable model hosts for identifying potential vectors of avian blood parasites. We studied haemosporidian infections in the Tengmalm's Owl (Aegolius funereus) in the Ore Mountains of the Czech Republic using molecular detection methods. Sex of owl nestlings was scored using molecular sexing based on fragment analysis of PCR-amplified CHD1 introns. Observed infection prevalences in nestlings and adult owls were 51 and 86 %, respectively. Five parasite lineages were detected. Most of the infections comprised the Leucocytozoon AEFUN02 and STOCC06 lineages that probably refer to distinct Leucocytozoon species. Other lineages were detected only sporadically. Mixed infections were found in 49 % of samples. The main factor affecting the probability of infection was host age. No effect of individual sex on infection probability was evidenced. The youngest infected nestling was 12 days old. High parasite prevalence in the Tengmalm's Owl nestlings suggests that insect vectors must enter nest boxes to transmit parasites before fledging. Hence, we placed sticky insect traps into modified nest boxes, collected potential insect vectors, and examined them for the presence of haemosporidian parasites using molecular detection. We trapped 201 insects which were determined as biting midges from the Culicoides genus and two black fly species, Simulium (Nevermannia) vernum and Simulium (Eusimulium) angustipes. Six haemosporidian lineages were detected in the potential insect vectors, among which the Leucocytozoon lineage BT2 was common to the Tengmalm's Owl and the trapped insects. However, we have not detected the most frequently encountered Tengmalm's Owl Leucocytozoon lineages AEFUN02 and STOCC06 in insects. PMID- 26365668 TI - Administration of pneumococcal vaccine in Hajj. Reply to Razavi SM and Salamati P. PMID- 26365669 TI - Interaction of dietary fat intake with APOA2, APOA5 and LEPR polymorphisms and its relationship with obesity and dyslipidemia in young subjects. AB - BACKGROUND: Diet is an important environmental factor that interacts with genes to modulate the likelihood of developing disorders in lipid metabolism and the relationship between diet and genes in the presence of other chronic diseases such as obesity. The objective of this study was to analyze the interaction of a high fat diet with the APOA2 (rs3813627 and rs5082), APOA5 (rs662799 and rs3135506) and LEPR (rs8179183 and rs1137101) polymorphisms and its relationship with obesity and dyslipidemia in young subjects. METHODS: The study included 200 young subjects aged 18 to 25 years (100 normal-weight and 100 obese subjects). Dietary fat intake was measured using the frequency food consumption questionnaire. Genotyping of polymorphisms was performed by PCR-RFLP. RESULTS: Individuals carrying the APOA5 56 G/G genotype with a high saturated fatty acid consumption (OR = 2.7, p = 0.006) and/or total fat (OR = 2.4, p = 0.018), associated with an increased risk of obesity. We also found that A/G + G/G genotypes of the 668 A/G polymorphism in the LEPR gene with an intake >= 12 g/d of saturated fatty acids, have 2.9 times higher risk of obesity (p = 0.002), 3.8 times higher risk of hypercholesterolemia (p = 0.002) and 2.4 times higher risk of hypertriglyceridemia (p = 0.02), than those with an intake <12 g/d of saturated fatty acids. Similarly, LEPR 668 A/G + G/G carriers with a high fat total intake had 3.0 times higher risk of obesity (p = 0.002) and 4.1 times higher risk of hypercholesterolemia (p = 0.001). CONCLUSION: Our results suggest that dietary fat intake modifies the effect of APOA5 and LEPR polymorphisms on serum triglycerides, cholesterol levels and obesity in young subjects. PMID- 26365670 TI - Increased Body Mass Index Is Associated with Congestive Heart Failure and Mortality in Adult Fontan Patients. AB - OBJECTIVE: Obesity affects adults with congenital heart disease (CHD). The effect of an increased body mass index (BMI) with respect to morbidity and mortality has not been evaluated in adults with complex CHD. Our objective was to evaluate the effects of increased BMI on heart failure and mortality in univentricular patients who had undergone Fontan palliation. METHODS: A query of Fontan patients' first appointments at the Washington University Center for Adults with CHD between 2007 and 2014 yielded 79 patients. BMI status as normal (<25 kg/m(2) ), overweight (>=25, <30 kg/m(2) ), and obese (>=30 kg/m(2) ) was established at the patient's first appointment. We analyzed demographics, diuretic requirements, New York Heart Association (NYHA) class, and laboratory values using Student's two-sample t-test and Fisher's exact test. Mortality was assessed via survival curves, and hazard ratios were compiled with proportional hazard modeling. RESULTS: The recent average BMI was significantly greater in patients with NYHA classes II-IV (29.3 +/- 9 kg/m(2) ) compared with asymptomatic patients (24.8 +/- 5.1 kg/m(2) , P = .006). Additionally, the average BMI of patients with a high diuretic requirement (>=40 mg/day IV furosemide equivalent) was obese, at 32.15 +/- 9.1 kg/m(2) , compared with 25.91 +/- 7.3 kg/m(2) for those on no or lower doses of diuretics (P = .009). Eighteen of the 79 patients met an endpoint of death, hospice placement, or cardiac transplant by the study conclusion. Kaplan Meier analysis from time of first appointment until recent follow-up revealed a significant association between time to combined endpoint and BMI class. Cox proportional hazard modeling with age adjustment yielded a hazard ratio of 3.2 (95% CI 1.096-9.379) for obesity upon first presentation to an adult CHD clinic. CONCLUSIONS: In patients with univentricular hearts and Fontan palliation, obesity is associated with symptomatic heart failure and mortality. PMID- 26365671 TI - Soluble urokinase plasminogen activator receptor (suPAR) is a novel, independent predictive marker of myocardial infarction in HIV-1-infected patients: a nested case-control study. AB - OBJECTIVES: Patients infected with HIV are at increased risk of myocardial infarction (MI). Increased plasma levels of the inflammatory biomarker soluble urokinase plasminogen activator receptor (suPAR) have been associated with increased risk of cardiovascular diseases (CVD), including MI in the general population. We tested suPAR as a predictive biomarker of MI in HIV-1-infected individuals. METHODS: suPAR levels were investigated in a nested case-control study of 55 HIV-1-infected cases with verified first-time MI and 182 HIV-1 infected controls with no known CVD. Controls were matched for age, gender, duration of antiretroviral therapy (ART), smoking and no known CVD. suPAR was measured in the four plasma samples available for each patient at different time points; 1, Before initiation of ART; 2, 3 months after initiation of ART; 3, 1 year before the case's MI; and 4, The last sample available before the case's MI. RESULTS: In unadjusted conditional regression analysis, higher levels of suPAR were associated with a significant increase in risk of MI at all time-points. Patients in the third and fourth suPAR quartiles had a three- to 10-fold higher risk of MI compared to patients in the lowest suPAR quartile at all time-points. suPAR remained a strong significant predictor of MI, when adjusting for HIV-1 RNA, total cholesterol, triglycerides and high-density lipoprotein. CONCLUSION: Elevated suPAR levels were associated with increased risk of MI in HIV-infected patients, suggesting that suPAR could be a useful biomarker for prediction of first-time MI in this patient group, even years before the event. PMID- 26365672 TI - Peroral Endoscopic Myotomy for Achalasia in a Thoracic Surgical Practice. AB - BACKGROUND: Peroral endoscopic myotomy (POEM) is a new option in the treatment of achalasia. It has typically been performed by general surgeons and gastroenterologists familiar with advanced endoscopic procedures. Our objective was to assess the initial experience and outcomes with POEM by a thoracic surgeon. METHODS: A retrospective chart review was performed of all patients who underwent POEM from October 2012 until December 2014. Pre- and post-POEM evaluation included upper endoscopy, high-resolution manometry, and a timed barium swallow. RESULTS: There were 35 patients (18 men and 17 women), with a median age of 53 years. Based on high-resolution manometry, there were 8 patients (23%) with type I, 21 (60%) with type II, and 5 (14%) with type III achalasia, and 1 patient had hypertensive lower esophageal sphincter. Prior therapy had been performed in 18 patients (51%). The POEM procedure was completed in all but 1 patient. On follow-up, dysphagia was improved in all patients. The Eckardt score was significantly reduced from 7 before POEM to 0 after POEM (p < 0.0001), and improved similarly for all manometric types of achalasia. Post-POEM upper endoscopy showed esophagitis in 55% of patients, but this condition resolved in all with acid suppression. Timed barium swallow showed a reduction of esophageal retention at 5 minutes from 63% before POEM to 5% after POEM. Ten patients had follow-up at 12 months or greater after POEM and the improvements persisted. CONCLUSIONS: Peroral endoscopic myotomy is a safe and effective therapy for achalasia. It provides reliable and persistent palliation of dysphagia and objective improvement in esophageal emptying. Esophagitis is common but resolves with acid suppression therapy. Thoracic surgeons with an interest in esophageal diseases and experience with endoscopy are encouraged to adopt the procedure. PMID- 26365673 TI - Functional and Biomechanical Performance of Stentless Extracellular Matrix Tricuspid Tube Graft: An Acute Experimental Porcine Evaluation. AB - BACKGROUND: Stentless porcine extracellular matrix tricuspid tubular valves have been developed for tricuspid valve reconstruction. The purpose of this study was to compare biomechanical and functional performance of native and tube graft valves in an acute porcine model. METHODS: Twenty-two 65-kg pigs were randomized to tube graft or control with native valve preservation. Anterior papillary muscle force was measured with a dedicated force transducer. Microtip pressure catheters were placed in the right atrium and ventricle. Leaflet motion and three dimensional valve geometry were evaluated using 13 sonomicrometry crystals: six in the tricuspid annulus, one on each leaflet free edge, one on each papillary muscle tip, and one in the right ventricular apex. RESULTS: No regurgitation and no significant differences in intracavitary pressures, annular motion, or leaflet excursion angles were observed after tube graft implantation (p > 0.05). Compared with the native valve, the tricuspid annulus, leaflet orifice area, annular diameters, and the septal segment of the annulus were significantly smaller in the tube graft group (p < 0.05). Maximum anterior papillary muscle force was significantly lower in the tube graft group (p < 0.005). The implantation technique led to an annular circumferential downsizing of 20% +/- 17%. CONCLUSIONS: An extracellular matrix tube graft implanted in the tricuspid position produces a competent valve with physiologic performance that, despite downsizing, makes the tube graft an attractive alternative to valve replacement. The downsizing of the implantation should be considered when planning tube graft size and may be potentially beneficial by relieving tension on the repaired tissue, thereby increasing durability. PMID- 26365674 TI - Treatment Strategies for Primary Tumors of the Heart in Children: A 10-Year Experience. AB - BACKGROUND: The goal of this study was to determine the optimal treatment strategy for children with primary tumors of the heart. METHODS: We reviewed 88 children with primary heart tumors in our center from January 2004 to December 2013. Operative patients were followed every 6 months in the first postoperative year and then regularly every 12 months; nonoperative patients were followed once a year after diagnosis. Demographic information of imaging, operative details, and postoperative data were obtained from medical records. Statistical analyses were carried out by means of Fisher's exact tests and Student's t test. RESULTS: Of the 23 patients who underwent surgical removal of the tumors (range, 12 days to 14.4 years; median, 1.3 years), 19 patients had stable postoperative hemodynamics, 4 had low cardiac output, and 2 patients died (mortality, 9%). The follow-up ranged from 6 months to 9 years; 2 patients had tumor recurrence, and 1 patient was lost to follow-up. The rest of the operative patients remained in normal sinus rhythm and had normal cardiac function. The 65 patients treated nonoperatively (range, 1 day to 14.4 years; median, 0.4 years) were followed closely for 1 month to 9.8 years; only 1 patient died (of unknown reasons), 1 patient received a cardiac transplant, and 9 patients were lost to follow-up. CONCLUSIONS: Operative resection is optimal for primary tumors of the heart in patients with obvious symptoms or hemodynamic changes. Rhabdomyomas have the potential for spontaneous regression, and nonoperative follow-up therefore is acceptable even if symptoms appear. Operative risk is greater in younger patients and in patients with cardiac valvular dysfunction. PMID- 26365676 TI - Metal-organic framework nanocrystals as sacrificial templates for hollow and exceptionally porous titania and composite materials. AB - We report a strategy that employs metal-organic framework (MOF) crystals in two roles for the fabrication of hollow nanomaterials. In the first role the MOF crystals provide a template on which a shell of material can be deposited. Etching of the MOF produces a hollow structure with a predetermined size and morphology. In combination with this strategy, the MOF crystals, including guest molecules in their pores, can provide the components of a secondary material that is deposited inside the initially formed shell. We used this approach to develop a straightforward and reproducible method for constructing well-defined, nonspherical hollow and exceptionally porous titania and titania-based composite nanomaterials. Uniform hollow nanostructures of amorphous titania, which assume the cubic or polyhedral shape of the original template, are delivered using nano- and microsized ZIF-8 and ZIF-67 crystal templates. These materials exhibit outstanding textural properties including hierarchical pore structures and BET surface areas of up to 800 m(2)/g. As a proof of principle, we further demonstrate that metal nanoparticles such as Pt nanoparticles, can be encapsulated into the TiO2 shell during the digestion process and used for subsequent heterogeneous catalysis. In addition, we show that the core components of the ZIF nanocrystals, along with their adsorbed guests, can be used as precursors for the formation of secondary materials, following their thermal decomposition, to produce hollow and porous metal sulfide/titania or metal oxide/titania composite nanostructures. PMID- 26365675 TI - Transcatheter Aortic Valve Replacement Versus Aortic Valve Bypass: A Comparison of Outcomes and Economics. AB - BACKGROUND: Transcatheter aortic valve replacement (TAVR) is currently offered to patients who are high-risk candidates for conventional surgical aortic valve replacement. For the past 37 years, off-pump aortic valve bypass (AVB) has been used in elderly patients at our center for this similarly high-risk group. Although TAVR and AVB were offered to similar patients at our center, comparisons of clinical outcomes and hospital economics for each strategy were not reported. METHODS: We reviewed the clinical and financial records of 53 consecutive AVB procedures performed since 2008 with the records of 51 consecutive TAVR procedures performed since 2012. Data included demographics, hemodynamics, The Society of Thoracic Surgeons (STS) risk score, extent of coronary disease, and ventricular function. Follow-up was 100% in both groups. Hospital financial information for both cohorts was obtained. Mean risk score for the TAVR group was 10.1% versus 17.6% for AVB group (p < 0.001). RESULTS: Kaplan-Meier hospital rates of 3- and 6-month survival and of 1-year survival were 88%, 86%, 81%, and 61% and 89%, 83%, 83%, and 70% for the TAVR and AVB groups, respectively (p = 0.781). Two patients who had undergone TAVR had a procedure-related stroke. The one stroke in an AVB recipient was late and not procedure related. At discharge, mild and moderate perivalvular and central aortic insufficiency were present in 31% and 16% of TAVR recipients, respectively; no AVB valve leaked. Transvalvular gradients were reduced to less than 10 mm Hg in both groups. The average hospital length of stay for the AVB-treated patients was 13 days, and it was 9 days for the TAVR-treated patients. Median hospital charges were $253,000 for TAVR and $158,000 for AVB. Mean payment to the hospital was $65,000 (TAVR) versus $64,000 (AVB), and the mean positive contribution margin (profit) to the hospital was $14,000 for TAVR versus $29,000 for AVB. CONCLUSIONS: TAVR and AVB relieve aortic stenosis and have similar and acceptable procedural mortality rates. AVB-treated patients had 1.75 times the STS risk score when compared with the TAVR cohort. Hospital charges for TAVR were nearly twofold those of AVB. Hospital reimbursement was similar, but AVB had two to four times the profit margin of TAVR. Longer follow-up for the TAVR cohort will determine whether survival is comparable to that after AVB at 3 and 5 years. PMID- 26365678 TI - alpha-Lipoic acid protects against the oxidative stress and cytotoxicity induced by cadmium in HepG2 cells through regenerating glutathione regulated by glutamate cysteine ligase. AB - Alpha-lipoic acid (alpha-LA) is an important antioxidant that is capable of regenerating other antioxidants, such as glutathione (GSH). In the present study, we examined the protective effects of alpha-LA against the oxidative stress and cytotoxicity induced by cadmium in human hepatoma cell lines (HepG2) and investigated if the process was mediated through regenerating GSH. Our results showed that after exposure to 25 MUM cadmium for 16 h, there was a significant decrease in the cell viability and glutathione levels and a significant increase in lipid peroxidation (p<0.01) compared with untreated cells. The presence of alpha-LA significantly attenuated cadmium-induced cytotoxicity and lipid peroxidation, and reversed cellular GSH levels compared with cadmium-treated cells (p<0.05). Compared with the cells treated with cadmium, co-treatment with alpha-LA and cadmium significantly increased the activities of gamma glutamylcysteine ligase (gamma-GCL), the rate limiting enzyme in GSH biosynthesis and the mRNA and the protein levels of gamma-GCL catalytic subunit (GCLC) and a modifier subunit (GCLM). In conclusion, our results indicated that alpha-LA is an effective agent to reduce the oxidative stress and cytotoxicity induced by cadmium by regenerating GSH levels through increasing the activities and the expressions of gamma-GCL. PMID- 26365677 TI - Direct production of XY(DMY-) sex reversal female medaka (Oryzias latipes) by embryo microinjection of TALENs. AB - Medaka is an ideal model for sex determination and sex reversal, such as XY phenotypically female patients in humans. Here, we assembled improved TALENs targeting the DMY gene and generated XY(DMY-) mutants to investigate gonadal dysgenesis in medaka. DMY-TALENs resulted in indel mutations at the targeted loci (46.8%). DMY-nanos3UTR-TALENs induced mutations were passed through the germline to F1 generation with efficiencies of up to 91.7%. XY(DMY-) mutants developed into females, laid eggs, and stably passed the Y(DMY-) chromosome to next generation. RNA-seq generated 157 million raw reads from WT male (WT_M_TE), WT female (WT_F_OV) and XY(DMY-) female medaka (TA_F_OV) gonad libraries. Differential expression analysis identified 144 up- and 293 down-regulated genes in TA_F_OV compared with WT_F_OV, 387 up- and 338 down-regulated genes in TA_F_OV compared with WT_M_TE. According to genes annotation and functional prediction, such as Wnt1 and PRCK, it revealed that incomplete ovarian function and reduced fertility of XY(DMY-) mutant is closely related to the wnt signaling pathway. Our results provided the transcriptional profiles of XY(DMY-) mutants, revealed the mechanism between sex reversal and DMY in medaka, and suggested that XY(DMY-) medaka was a novel mutant that is useful for investigating gonadal dysgenesis in phenotypic female patients with the 46, XY karyotype. PMID- 26365679 TI - Failure to interact with Brd4 alters the ability of HPV16 E2 to regulate host genome expression and cellular movement. AB - The E2 protein of the carcinogen human papillomavirus 16 (HPV16) regulates replication and transcription of the viral genome in association with viral and cellular proteins. Our previous work demonstrated that E2 can regulate transcription from the host genome. E2 can activate transcription from adjacent promoters when located upstream using E2 DNA binding sequences and this activation is dependent upon the cellular protein Brd4; this report demonstrates that a Brd4 binding E2 mutant alters host genome expression differently from wild type E2. Of particular note is that highly down regulated genes are mostly not affected by failure to interact with Brd4 suggesting that the E2-Brd4 interaction is more responsible for the transcriptional activation of host genes rather than repression. Therefore failure to interact efficiently with Brd4, or altered levels of Brd4, would alter the ability of E2 to regulate the host genome and could contribute to determining the outcome of infection. PMID- 26365681 TI - Conserved tegument protein complexes: Essential components in the assembly of herpesviruses. AB - One of the structural components of herpesviruses is a protein layer called the tegument. Several of the tegument proteins are highly conserved across the herpesvirus family and serve as a logical focus for defining critical interactions required for viral assembly. A number of studies have helped to elucidate a role for conserved tegument proteins in the process of secondary envelopment during the course of herpesviral assembly. This review highlights how these tegument proteins directly contribute to bridging the nucleocapsid and envelope of virions during secondary envelopment. PMID- 26365682 TI - Polarization-resolved spectroscopy imaging of grain boundaries and optical excitations in crystalline organic thin films. AB - Exploration of optical properties of organic crystalline semiconductors thin films is challenging due to submicron grain sizes and the presence of numerous structural defects, disorder and grain boundaries. Here we report on the results of combined linear dichroism (LD)/ polarization-resolved photoluminescence (PL) scanning microscopy experiments that simultaneously probe the excitonic radiative recombination and the molecular ordering in solution-processed metal-free phthalocyanine crystalline thin films with macroscopic grain sizes. LD/PL images reveal the relative orientation of the singlet exciton transition dipoles at the grain boundaries and the presence of a localized electronic state that acts like a barrier for exciton diffusion across the grain boundary. We also show how this energy barrier can be entirely eliminated through the optimization of deposition parameters that results in films with large grain sizes and small-angle boundaries. These studies open an avenue for exploring the influence of long range order on exciton diffusion and carrier transport. PMID- 26365680 TI - Decoding protein networks during virus entry by quantitative proteomics. AB - Virus entry into host cells relies on interactions between viral and host structures including lipids, carbohydrates and proteins. Particularly, protein protein interactions between viral surface proteins and host proteins as well as secondary host protein-protein interactions play a pivotal role in coordinating virus binding and uptake. These interactions are dynamic and frequently involve multiprotein complexes. In the past decade mass spectrometry based proteomics methods have reached sensitivities and high throughput compatibilities of genomics methods and now allow the reliable quantitation of proteins in complex samples from limited material. As proteomics provides essential information on the biologically active entity namely the protein, including its posttranslational modifications and its interactions with other proteins, it is an indispensable method in the virologist's toolbox. Here we review protein interactions during virus entry and compare classical biochemical methods to study entry with novel technically advanced quantitative proteomics techniques. We highlight the value of quantitative proteomics in mapping functional virus entry networks, discuss the benefits and limitations and illustrate how the methodology will help resolve unsettled questions in virus entry research in the future. PMID- 26365683 TI - Acinetobacter baumannii in Southern Croatia: clonal lineages, biofilm formation, and resistance patterns. AB - BACKGROUND: Acinetobacter baumannii is one of the most prevalent causes of severe hospital-acquired infections and is responsible for the dramatic increase in carbapenem resistance in Croatia in the last 5 years. Such data have encouraged multicenter research focused on the organism's ability to form biofilm, susceptibility to antibiotics, and particular genotype lineage. METHODS: Biofilm formation in 109 unrelated clinical isolates of A. baumannii recovered in six cities of Southern Croatia was investigated. Genotyping was performed by pulsed field gel electrophoresis and antibiotic profile was tested by applying the disc diffusion method and confirmed by determining the minimum inhibitory concentrations. The ability to form biofilm in vitro was determined from overnight cultures of the collected isolates on microtiter plates, after staining with crystal violet, and quantified at 570 nm after solubilization with ethanol. The statistical relevance was calculated in an appropriate program with level of statistical confidence. RESULTS: There was no significant difference in biofilm formation due to the genotype lineage. Isolates collected from intensive care units (ICUs) and isolated from respiratory samples were more likely to create a biofilm compared with isolates from other departments and other samples. There was a significant difference in the ability to produce biofilm in relation to antibiotic resistance pattern. A large proportion of A. baumannii isolates that were resistant to ampicillin/sulbactam, carbapenems, and amikacin were found to be biofilm-negative. In contrast, isolates susceptible and intermediately susceptible to ampicillin/sulbactam, carbapenems, and amikacin were biofilm producers. CONCLUSION: Clinical isolates of A. baumannii from respiratory samples in ICUs with a particular susceptibility pattern are more prone to form biofilm. PMID- 26365684 TI - Use of sofosbuvir-based direct-acting antiviral therapy for hepatitis C viral infection in patients with severe renal insufficiency. AB - Sofosbuvir-based direct-acting antiviral therapy revolutionized the treatment of hepatitis C virus (HCV) infection. However, sofosbuvir use is not approved for patients with severe renal insufficiency (estimated glomerular filtration (eGFR) rate below 30 ml/min) or end-stage renal disease (ESRD) based on concerns raised during premarket animal testing over hepatobiliary and cardiovascular toxicity in this population. We report the first published data on use of sofosbuvir-based regimens in patients with severe renal insufficiency and ESRD, focusing on clinical efficacy and safety. Six patients were treated with full dose sofosbuvir; three received sofosbuvir and simeprevir, two received sofosbuvir and ribavirin, and one received sofosbuvir, ribavirin, and interferon. Three of the patients had cirrhosis. On-treatment viral suppression was 100% and sustained virological response (SVR) rate at 12 weeks was 67%. One patient had to discontinue antiviral therapy early due to side effects. No hepatobiliary or cardiovascular toxicity was reported. PMID- 26365685 TI - The changing landscape of adverse drug events associated with chronic hepatitis C virus therapy. AB - Treatment of chronic hepatitis C virus (HCV) therapy has rapidly changed since the approval of IFN in the 1990s. Early treatment brought about significant and therapy limiting adverse drug events (ADEs) such as anemia. Since the direct acting antivirals were first approved in 2011 and then advanced in 2013, treatment-related ADEs and therapy discontinuations have rapidly decreased, while sustained virologic response rates have significantly increased. As the market for treating chronic HCV therapy has changed, so too has the ADE profile clinicians may need to manage. PMID- 26365686 TI - Kin recognition by self-referent phenotype matching in plants. PMID- 26365687 TI - Distress related to subclinical negative symptoms in a non-clinical sample: Role of dysfunctional attitudes. AB - Negative symptoms are a prominent feature of schizophrenia that are intimately linked to poor outcomes characterizing the illness. One mechanistic model suggests that these symptoms are produced and maintained, at least in part, through maladaptive attitudes. Beyond mechanisms, it remains phenomenologically unclear if these symptoms are particularly distressing. In the present study we examined whether subclinical negative symptoms evaluated in a non-clinical sample of young adults (N=370) were distressful or bothersome to participants and, further, whether these symptoms were associated with dysfunctional attitudes. We found that greater severity of subclinical negative symptoms such as amotivation and anhedonia were associated with higher ratings of distress specifically attributable to these symptoms. This relationship held even after controlling for severity of depressive symptoms. Moreover, greater negative symptom burden was associated with greater endorsement of defeatist performance beliefs. Negative symptoms expressed in the general population were found to be particularly distressing. Maladaptive cognitive schemas are implicated in the expression of these symptoms, as well as the amount of distress these symptoms instil. A greater understanding of the mechanisms underlying negative symptoms, including both neurobiological and cognitive, is needed in order to effectively develop treatment strategies for these disabling symptoms. PMID- 26365688 TI - Disease recognition is related to specific autobiographical memory deficits in alcohol-dependence. AB - The particularly high treatment gap in alcohol-dependence suggests the existence of important barriers to treatment decision and in particular difficulties in problem recognition. This study tested the relation between problem recognition and self-related memories. Forty-one recently detoxified alcohol-dependent individuals (AD) were compared to twenty alcoholic subjects that were abstinent for 6 months or more (recruited among alcoholics-anonymous (AA)), and to twenty controls on autobiographical memories elicited by pictures depicting or not alcohol using the autobiographical memory test. Autonoetic consciousness was measured with the Remember/Know paradigm. We tested whether memories performances were related with data obtained on the readiness to change questionnaire (RCQ) or with consciousness of the severity of drinking. AD subjects provided less specific memories than control and AA subjects, and fewer Remember responses than controls. The deficits in AD subjects were not specific for memories elicited by pictures depicting alcohol, suggesting a global deficit. Autobiographical memories specificity was negatively correlated to scores of consciousness of the severity of drinking but not to RCQ. Our results support potential recovery of autobiographical memory with abstinence. AD's deficits in autobiographical memory were related to capacities to recognize the severity and therefore may be a barrier to treatment decision. PMID- 26365689 TI - A four-year follow-up controlled study of stress response and symptom persistence in Brazilian children and adolescents with attention deficit disorder and hyperactivity (ADHD). AB - This study evaluated children and adolescents with Attention Deficit Disorder andHyperactivity Disorder (ADHD), reassessing them at a four-year follow-up. Their cortisol response to a stress stimulus was measured twice. ADHD symptom persistence, development of comorbidities, and psychostimulant usage were also reassessed. The initial sample consisted of 38 ADHD patients and 38 healthy controls, age ranging 6-14. At the follow-up, there were 37 ADHD patients and 22 healthy controls, age ranging 10-18. ADHD was classified as persistent if the patients fulfilled all DSM IV criteria for syndromic or subthreshold or had functional impairment. Salivary cortisol samples were collected prior to the application of a cognitive stressor (Continuous Performance Test - CPT), and at three time intervals afterwards at baseline and at the follow-up. Their reassessment showed that 75% had persistent symptoms, psychiatric comorbidities (oppositional defiant and behavioral disorders), functional and academic impairement. Only seven patients were on medication. The ADHD group's cortisol levels were lower than those measured four years earlier, but cortisol concentrations were similar for both ADHD and control groups at the four-year follow-up. The cortisol results suggest that HPA axis reactivity could be a marker differentiating ADHD from ADHD with comorbidities. PMID- 26365690 TI - Set-shifting abilities, mood and loss of control over eating in binge eating disorder: An experimental study. AB - Executive functions play an important role in problem-solving and self-control. Set-shifting is an aspect of executive functioning and represents cognitive flexibility. The inability to control eating in Binge Eating Disorder (BED) may imply deficits in set-shifting which could be exacerbated by negative mood and depressive symptoms. The aim of the study was to test whether there is a causal relationship between set-shifting ability, changes in mood and loss of control over eating in BED. Seventy-five participants diagnosed with BED were randomly assigned to a negative or neutral mood induction. Set-shifting abilities, depressive symptoms, current mood and loss of control over eating were assessed. Having depressive symptoms and poorer set-shifting abilities resulted in a more negative mood after a negative mood induction, whereas this was not observed in the neutral mood induction. Post-hoc analyses revealed that individuals with poorer set-shifting abilities and more changes in negative mood, experienced more feelings of loss of control over eating than individuals whose set-shifting abilities were better and whose mood did not change. The results suggest that both depressive symptoms and deficits in set-shifting abilities may decrease an individual's ability to handle negative affect and increase loss of control over eating in individuals with BED. PMID- 26365691 TI - Epidemiology of adult acute myeloid leukemia: Impact of exposures on clinical phenotypes and outcomes after therapy. AB - BACKGROUND: An increased risk of adult myeloid leukemia (AML) has recently been associated with lifestyle and environmental exposures, including obesity, smoking, some over the counter medications, and rural/farm habitats in case control studies. The association of these exposures with AML cytogenetic categories, outcomes after therapy, and overall survival is unknown. METHODS: Relevant exposures were evaluated in a cohort of 295 consecutive AML patients diagnosed and treated at Mayo Clinic in Florida and Arizona. Standard cytogenetic risk categories were applied and reviewed in a central cytogenetic laboratory. The association of epidemiologic exposures with cytogenetic risk, complete remission after therapy, and overall survival was evaluated using logistic and Cox regression models. RESULTS: A significant association between obesity and intermediate-abnormal cytogenetics was identified (OR: 1.94, P=0.025). Similarly, those with secondary AML were more likely to have poor risk (OR: 2.55, P<0.001) and less likely to have intermediate normal (OR: 0.48, P=0.003) cytogenetics. In multivariate analysis, overall survival was improved for patients >= 60 years receiving intensive (RR: 0.21, P<0.001) and non-intensive therapy (RR: 0.40, P<0.001 compared to no treatment, and was lower for users of tobacco (RR 1.39, P=0.032), and those with poor risk cytogenetics (RR: 3.96, P=0.002) or poor performance status (RR: 1.69, P<0.001). Furthermore, an association between statin use at the time of diagnosis (OR: 2.89, P=0.016) and increased complete remission after intensive chemotherapy was identified, while prior solid organ transplantation was associated with significantly lower complete remission rate after therapy (OR: 0.10, P=0.035). CONCLUSION: Our results provide evidence that specific epidemiologic exposures, including obesity, are significantly associated with unique AML cytogenetic risk categories and response to therapy. This supports a link between patient lifestyles, clinical exposures, and leukemogenesis. PMID- 26365692 TI - Bayesian dose-response analysis for epidemiological studies with complex uncertainty in dose estimation. AB - Most conventional risk analysis methods rely on a single best estimate of exposure per person, which does not allow for adjustment for exposure-related uncertainty. Here, we propose a Bayesian model averaging method to properly quantify the relationship between radiation dose and disease outcomes by accounting for shared and unshared uncertainty in estimated dose. Our Bayesian risk analysis method utilizes multiple realizations of sets (vectors) of doses generated by a two-dimensional Monte Carlo simulation method that properly separates shared and unshared errors in dose estimation. The exposure model used in this work is taken from a study of the risk of thyroid nodules among a cohort of 2376 subjects who were exposed to fallout from nuclear testing in Kazakhstan. We assessed the performance of our method through an extensive series of simulations and comparisons against conventional regression risk analysis methods. When the estimated doses contain relatively small amounts of uncertainty, the Bayesian method using multiple a priori plausible draws of dose vectors gave similar results to the conventional regression-based methods of dose response analysis. However, when large and complex mixtures of shared and unshared uncertainties are present, the Bayesian method using multiple dose vectors had significantly lower relative bias than conventional regression-based risk analysis methods and better coverage, that is, a markedly increased capability to include the true risk coefficient within the 95% credible interval of the Bayesian-based risk estimate. An evaluation of the dose-response using our method is presented for an epidemiological study of thyroid disease following radiation exposure. PMID- 26365693 TI - Immunizing nomadic children and livestock--Experience in North East Zone of Somalia. AB - Nomads and pastoralists represent around 30% of the population of North East zone of Somalia (Puntland) and have very limited access to basic health including immunization. During the 2013-2014 polio outbreak in Somalia, an increase number of polio cases notified health services among these underserved communities highlighted the urgent need to devise innovative strategies to reach them. Harnessing the high demand for veterinary services among pastoralist communities, the Ministry of Health and the Ministry of Livestock, with support from UNICEF, WHO and FAO launched an integrated human and animal vaccination campaign on 19 October 2014. Over 30 days, 20 social mobilizers conducted shelter to shelter social mobilization and interpersonal communication for nomadic/pastoralist hamlets, 20 human vaccination teams, accompanied by local community elders, traveled with animal vaccination teams to administer polio and measles vaccination to pastoralist communities in the 5 regions of Puntland. 26,393 children (0 to 10 years) received Oral Polio Vaccine (OPV) out of which 34% for the first time ever; 23,099 were vaccinated against measles. and 12,556 Vitamin A. Despite various operational challenges and a significantly higher operational cost of $6.2 per child reached with OPV, the integrated human and animal vaccination campaign was effective in reaching the unvaccinated children from nomadic and pastoralist communities of Somalia. PMID- 26365694 TI - Interactive effects of warming, eutrophication and size structure: impacts on biodiversity and food-web structure. AB - Warming and eutrophication are two of the most important global change stressors for natural ecosystems, but their interaction is poorly understood. We used a dynamic model of complex, size-structured food webs to assess interactive effects on diversity and network structure. We found antagonistic impacts: Warming increases diversity in eutrophic systems and decreases it in oligotrophic systems. These effects interact with the community size structure: Communities of similarly sized species such as parasitoid-host systems are stabilized by warming and destabilized by eutrophication, whereas the diversity of size-structured predator-prey networks decreases strongly with warming, but decreases only weakly with eutrophication. Nonrandom extinction risks for generalists and specialists lead to higher connectance in networks without size structure and lower connectance in size-structured communities. Overall, our results unravel interactive impacts of warming and eutrophication and suggest that size structure may serve as an important proxy for predicting the community sensitivity to these global change stressors. PMID- 26365695 TI - Effect of iron deficiency anaemia on HbA1c levels is dependent on the degree of anaemia. AB - OBJECTIVES: Studies suggest that iron deficiency anaemia (IDA) is associated with higher HbA1c levels. We conducted a control-case study to investigate the effect of IDA on HbA1c levels, measured by two commonly used methods, in non-diabetic individuals. DESIGN AND METHODS: A total of 122 patients were included, 61 patients with IDA and 61 patients without anaemia. HbA1c was measured by both ion exchange HPLC Variant II Turbo BioRad and immunoturbidimetry (IT) Tina Quant II Roche Diagnostics in each sample. HbA1c results were compared between groups. For correlation analysis, patients were considered altogether. RESULTS: There was a significant difference between the results of HbA1c in patients with IDA [HPLC 5.6 +/- 0.4% (38 +/- 4.4 mmol/mol) and IT 5.7 +/- 0.4% (39 +/- 4.4 mmol/mol)] and those measured in patients without anaemia [HPLC 5.3 +/- 0.4% (34 +/- 4.4 mmol/mol) and IT 5.3 +/- 0.3% (34 +/- 3.3 mmol/mol)], (p < 0.001). Significant negative correlations were observed between total haemoglobin (Hb), haematocrit, mean corpuscular volume (MCV) and ferritin with HbA1c values measured by IT (r = 0.557; r = - 0.539; r = - 0.488; r = - 0.499; p < 0.01; respectively). These negative correlations were weaker with HbA1c measured by HPLC (r = - 0.272; r = - 0.250; r = - 0.273; r = - 0.229 for Hb, haematocrit, MCV and ferritin; p < 0.05; respectively). HbA1c results were higher in patients with moderate and severe anaemia. However mild anaemia did not show significant effects on HbA1c results measured by both methods. CONCLUSIONS: IDA affects HbA1c results and this effect is dependent on anaemia degree. These upward changes are statistically significant but they may be not clinically relevant when the overall variability of the HbA1c test is considered. The presence of slight anaemia is likely to have a minor effect on HbA1c levels favouring its use to diagnose diabetes in patients with mild anaemia. PMID- 26365697 TI - Advantages of the lipoprotein-associated phospholipase A2 activity assay. AB - OBJECTIVES: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is increased in circulation in patients at higher risk of coronary heart disease (CHD) events and stroke. Therefore, measurement of Lp-PLA2 can be used as an adjunct to traditional cardiovascular risk factors for identifying individuals at higher risk of cardiovascular events. Recently, a reagent for measuring Lp-PLA2 activity (diaDexus, San Francisco, CA) received FDA approval. Here we evaluate the assay performance of the Lp-PLA2 activity assay. METHODS: Lp-PLA2 activity assay reagent performance was evaluated on an open user-defined channel on a Cobas 6000/c501 (Roche Diagnostics, Indianapolis, IN) using a 5-point calibration curve (0-400nmol/min/mL). Analytical performance was established for the following parameters: precision, linearity, accuracy, analytical sensitivity, analytical specificity, reference interval, reagent lot-to-lot comparison, specimen type, on board reagent stability, and sample stability. RESULTS: Assay limit of detection was determined to be 7.8nmol/min/mL with an average %CV of 2.8%. Precision studies revealed a coefficient of variation <=1.6% between 79 and 307nmol/min/mL and accuracy was demonstrated between 4.8-368.7nmol/min/mL. Comparable results were generated in paired SST serum and EDTA plasma. No age association was found with Lp-PLA2 activity at the 95th percentile however a gender association was identified resulting in gender-specific 95th percentile limits in a healthy reference population. No bias was found when comparing results from several different lots of assay reagent. Lp-PLA2 activity results are extremely stable in both serum and EDTA plasma under refrigerate and frozen storage conditions up to 31days. CONCLUSIONS: Lp-PLA2 activity assay displays accurate and precise performance characteristics on the Cobas c501 platform. The assay performance is significantly improved over the predecessor immunoassay allowing for adoption of Lp-PLA2 activity in clinical practice. PMID- 26365696 TI - Development and validation of an immunosensor for monocyte chemotactic protein 1 using a silicon photonic microring resonator biosensing platform. AB - OBJECTIVES: We report the development of an optical immunosensor for the detection of monocyte chemotactic protein 1 (MCP-1) in serum samples. MCP-1 is a cytokine that is an emerging biomarker for several diseases/disorders, including ischemic cardiomyopathy, fibromyalgia, and some cancers. DESIGN AND METHODS: The detection of MCP-1 was achieved by performing a sandwich immunoassay on a silicon photonic microring resonator sensor platform. The resonance wavelengths supported by microring sensors are responsive to local changes in the environment accompanying biomarker binding. This technology offers a modularly multiplexable approach to detecting analyte localization in an antibody-antigen complex at the sensor surface. RESULTS: The immunosensor allowed the rapid detection of MCP-1 in buffer and spiked human serum samples. An almost 2 order of magnitude linear range was observed, between 84.3 and 1582.1pg/mL and the limits of blank and detection were determined to be 0.3 and 0.5pg/mL, respectively. The platform's ability to analyze MCP-1 concentrations across a clinically-relevant concentration range was demonstrated. CONCLUSIONS: A silicon photonic immunosensor technology was applied to the detection of clinically-relevant concentrations of MCP-1. The performance of the sensor was validated through a broad dynamic range and across a number of suggested clinical cut-off values. Importantly, the intrinsic scalability and rapidity of the technology makes it readily amenable to the simultaneous detection of multiplexed biomarker panels, which is particularly needed for the clinical realization of inflammatory diagnostics. PMID- 26365698 TI - Multipronged Design of Light-Triggered Nanoparticles To Overcome Cisplatin Resistance for Efficient Ablation of Resistant Tumor. AB - Chemotherapeutic drugs frequently encounter multiple drug resistance in the field of cancer therapy. The strategy has been explored with limited success for the ablation of drug-resistant tumor via intravenous administration. In this work, the rationally designed light-triggered nanoparticles with multipronged physicochemical and biological features are developed to overcome cisplatin resistance via the assembly of Pt(IV) prodrug and cyanine dye (Cypate) within the copolymer for efficient ablation of cisplatin-resistant tumor. The micelles exhibit good photostability, sustained release, preferable tumor accumulation, and enhanced cellular uptake with reduced efflux on both A549 cells and resistant A549R cells. Moreover, near-infrared light not only triggers the photothermal effect of the micelles for remarkable photothermal cytotoxicity, but also leads to the intracellular translocation of the micelles and reduction-activable Pt(IV) prodrug into cytoplasm through the lysosomal disruption, as well as the remarkable inhibition on the expression of a drug-efflux transporter, multidrug resistance-associated protein 1 (MRP1) for further reversal of drug resistance of A549R cells. Consequently, the multipronged effects of light-triggered micelles cause synergistic cytotoxicity against both A549 cells and A549R cells, and thus efficient ablation of cisplatin-resistant tumor without regrowth. The multipronged features of light-triggered micelles represent a versatile synergistic approach for the ablation of resistant tumor in the field of cancer therapy. PMID- 26365699 TI - Circulating Dickkopf-1 in hypoxic ischemic neonates. AB - OBJECTIVE: The current study aimed to determine the serum level of Dickkopf-1 (Dkk-1) in peripheral blood of neonates with hypoxic ischemic encephalopathy (HIE). METHODS: We measured serum levels of Dkk-1 by ELISA in neonates with HIE (n = 20) within 24 h from symptom onset and in healthy controls (n = 20). RESULTS: Dkk-1 serum levels increased significantly in HIE neonates than in healthy control. DKK-1 serum levels increased significantly in HIE neonates with convulsion, using multiple anti-convulsant drugs and those complicated with cranial ultrasound changes. Serum DKK-1 levels increased significantly in severe HIE patients. CONCLUSION: Our study provides for the first time the evidence of releasing Dkk-1 into the circulation of neonates with HIE with higher level in severe degree. PMID- 26365700 TI - 3D shapes of aryl(dihydro)naphthothiophenes: a comprehensive and structural study. AB - Convenient access to new aryl(dihydro)naphthothiophenes is described using a common beta-chloroacrolein derivative. Our strategy is based on the construction of a condensed thiophene ring prior to a Suzuki-Miyaura coupling and allowed installing various substituents at the molecular platform. The overall shapes of these architectures were confirmed by X-ray analyses and were in good agreement with theoretical calculations. It has been established that the relative orientation between all fragments that composed molecules within this series is strongly related to both steric and electronic factors. Contribution of these key parameters revealed to be crucial to rationalize attempts to prepare fluorenone and fluorene derivatives from aryl(dihydro)naphthothiophene platforms. PMID- 26365701 TI - Interventions to reduce nurses' medication administration errors in inpatient settings: A systematic review and meta-analysis. AB - BACKGROUND AND OBJECTIVES: Serious medication administration errors are common in hospitals. Various interventions, including barcode-based technologies, have been developed to help prevent such errors. This systematic review and this meta analysis focus on the efficacy of interventions for reducing medication administration errors. The types of error and their gravity were also studied. METHODS: MEDLINE, EMBASE, the Cochrane Library and reference lists of relevant articles published between January 1975 and August 2014 were searched, without language restriction. Randomized controlled trials, interrupted time-series studies, non-randomized controlled trials and controlled before-and-after studies were included. Studies evaluating interventions for decreasing administration errors based on total opportunity for error method were included. Nurses administering medications to adult or child inpatients were considered eligible as participants. Two reviewers independently assessed studies for eligibility, extracted data and assessed the risk of bias. The main outcome was the error rate without wrong-time errors measured at study level. A random effects model was used to evaluate the effects of interventions on administration errors. RESULTS: 5312 records from electronic database searches were identified. Seven studies were included: five were randomized controlled trials (including one crossover trial) and two were non-randomized controlled trials. Interventions were training related (n=4; dedicated medication nurses, interactive CD-ROM program, simulation based learning, pharmacist-led training program), and technology-related (n=3; computerized prescribing and automated medication dispensing systems). All studies were subject to a high risk of bias, mostly due to a lack of blinding to outcome assessment and a risk of contamination. No difference between the control group and the intervention group was found (OR=0.72 [0.39; 1.34], p=0.3). No fatal error was observed in the three studies evaluating the gravity of errors. CONCLUSIONS: This review did not find evidence that interventions can effectively decrease administration errors. In addition, most studies had a high risk of bias. More evaluation studies with stronger designs are required. PMID- 26365702 TI - Single immunization with a recombinant multiple-epitope protein induced protection against FMDV type Asia 1 in cattle. AB - To develop recombinant epitope vaccines against the foot-and-mouth disease virus (FMDV) serotype Asia 1, genes encoding six recombinant proteins (A1-A6) consisting of different combinations of B-cell and T-cell epitopes from VP1 capsid protein (VP1) of FMDV were constructed. These proteins were expressed in Escherichia coli and used to immunize animals. Our results showed that A6 elicited higher titers of neutralizing antibodies after single inoculation in guinea pigs than did the other five recombinant proteins, as determined by micro neutralization tests. In addition, a strong lymphocyte proliferation response and Th1 type immunity were observed in splenocytes from the mice immunized with A6. Further tests carried out in cattle demonstrated that a single inoculation with A6 generated comparable levels of neutralizing antibodies as inactivated vaccine and protected 4 of 5 cattle against challenge with FMDV type Asia 1. Our results suggest that A6 might be a promising recombinant vaccine against FMDV type Asia 1 in cattle. PMID- 26365703 TI - Glomerular and tubular functions in children with different forms of beta thalassemia. AB - BACKGROUND: Although there are many available data about renal involvement in patients with beta thalassemia major (TM), the changes in renal functions of other types, such as thalassemia intermedia (TI) and thalassemia minor (TMin), were reported less. Therefore, we aimed to evaluate renal tubular and glomerular functions in patients with three types of beta thalassemia. METHODS: This prospective case-control study was conducted on 118 beta-thalassemia patients (49 in TM, 18 in TI and 51 TMin) and 51 healthy controls. Glomerular functions [estimated glomerular filtration rate (GFR), serum cystatin C and urinary protein creatinine ratio] and tubular functions [fractioned sodium excretion (FENa), tubular reabsorption of phosphorus, urinary excretion of uric acid, levels of retinol-binding protein, alpha-1 macroglobulin (alpha-1M), and beta-2 microglobulin, calcium creatinine ratio] were assessed in all patients and controls. RESULTS: The mean ages of the groups and controls at presentation were similar. Although GFR was similar in all patients and control groups, serum levels of cystatin C in patients with TM and TI were significantly higher compared to TMin and controls. Alpha-1M, FENa, urinary excretion of uric acid, and urine protein/creatinine ratio in TM and TI groups were significantly higher than the others. Mean cystatin C level was also higher in patients with TMin compared the controls. However, there were no significant differences according to all tubular and other glomerular functions between TMin and control groups. CONCLUSIONS: Although all types of beta thalassemia patients should be closely monitored to prevent further decrease in renal functions, the patients with TI should be considered to have a higher risk of glomerular and tubular deterioration as well as TM. PMID- 26365705 TI - The effect of replacing soya bean oil with glycerol in diets on performance, egg quality and egg fatty acid composition in laying hens. AB - The objective of this experiment was to replace soya bean oil with glycerol in laying hen diets and assess the change's effect on performance, parameters of egg quality and the egg fatty acid profile. A total of 60 44-week-old Hy-Line W36 laying hens were distributed according to a completely randomised experimental design into four treatments consisting of glycerol substitutions for soya bean oil dietary at varying inclusion levels (0%, 25%, 50% and 75%), with five replicates of three birds each. Dietary treatments had no significant effect on BW change, egg production, feed intake, feed conversion ratio, egg weight and egg mass of laying hens. The inclusion of glycerol in the diet of laying hens had no significant effect on egg specific gravity, eggshell breaking strength, eggshell weight, eggshell thickness, egg shape index, albumen index, yolk index, haugh unit, albumen pH, yolk pH and egg yolk colour values. The inclusion of glycerol in the diet of laying hens had no significant effect on palmitic, palmitoleic, stearic, oleic and linolenic acid contents of the egg yolk. The linoleic acid and polyunsaturated fatty acid contents of the egg yolk significantly decreased with the higher levels of dietary glycerol supplementation (P<0.05). The results of this study show that it is possible to replace 75% of soya bean oil (4.5% in diet) with glycerol. PMID- 26365704 TI - Teaching Translational Research to Medical Students: The New York University School of Medicine's Master's of Science in Clinical Investigation Dual-Degree Program. AB - To develop the next generation of translational investigators, New York University School of Medicine (NYUSOM) and the NYU-NYC Health and Hospitals Corporation Clinical and Translational Science Institute (NYU-HHC CTSI) developed the Master's of Science in Clinical Investigation dual-degree (MD/MSCI) program. This 5-year program dedicates 1 year to coursework and biomedical research, followed by a medical school/research overlap year, to prepare students for academic research careers. This paper details the MD/MSCI program's curriculum and approach to mentorship, describes the research/professional interests of students, and reports student productivity. In the first 4 years of the program (2010-2014) 20 students were matriculated; 7 (35%) were women, and 12 (60%) research projects were in surgical specialties. To date, 14 students have applied to residency, and half pursued surgical residency programs. Our students have produced 68 accepted abstracts, 15 abstracts in submission, 38 accepted papers, and 24 papers in submission. Despite the time-limited nature of this program, additional training in research design and implementation has promoted a high level of productivity. We conclude that dual-degree training in medicine and translational research is feasible for medical students and allows for meaningful participation in valuable projects. Follow-up is warranted to evaluate the academic trajectory of these students. PMID- 26365706 TI - Alkynol natural products target ALDH2 in cancer cells by irreversible binding to the active site. AB - Falcarinol and stipudiol are natural products with potent anti-cancer activity found in several vegetables. Here, we use a chemical proteomic strategy to identify ALDH2 as a molecular target of falcarinol in cancer cells and confirm enzyme inhibition via covalent alkylation of the active site. Furthermore, the synthesis of stipudiol led to the observation that ALDH2 exhibits preference for alkynol-based binders. Inhibition of ALDH2 impairs detoxification of reactive aldehydes and limits oxidative stress response, two crucial pathways for cellular viability. PMID- 26365707 TI - Synthesis of 2-(14)C-iminothiolane and 2-(13)C,(15)N-iminothiolane (Traut's reagent). AB - 2-Iminothiolane has found utility in the growing area of antibody-drug conjugates by serving as a lysine-thiolating agent and the junction between the antibody and the cytotoxic payload during random conjugation of a monoclonal antibody. 2-(14)C Iminothiolane was prepared from commercially available [(14)C]KCN using a four step sequence in an overall 10% radiochemical yield. Stable-labeled 2-(13)C,(15)N iminothiolane was also prepared from [(13)C(15)N]KCN in a similar manner. The labeled Traut's reagent produced by this sequence showed comparable reactivity as the commercially available unlabeled reagent with a representative monoclonal antibody and could serve as highly informative analytical tools to investigate antibody-drug conjugate formation via the random conjugation process. PMID- 26365709 TI - Norharmane rhenium(I) polypyridyl complexes: synthesis, structural and spectroscopic characterization. AB - Two novel Re(i) complexes with the general formula fac-[Re(CO)3(L)(nHo)]CF3SO3, where L = 2,2'-bipyridine (bpy) or 1,10 phenanthroline (phen) and nHo (9H pyrido[3,4-b]indole; norharmane) have been synthesized. The Re(i)-nHo complexes were characterized by structural X-ray diffraction, (1)H and (13)C NMR, UV-vis absorption and FT-IR spectroscopy, and by a combination of two mass spectrometry techniques, namely ESI-MS and UV-MALDI-MS. All characterizations showed that nHo is coordinated to the metal atom by the pyridine nitrogen of the molecule. X-ray structural analysis revealed that the crystal lattices for both complexes are further stabilized by a strong >N-HO bond between the pyrrole NH group of the pyridoindole ligand and one oxygen atom of the trifluoromethanesulfonate counter ion. Ground state geometry optimization by DFT calculations showed that in fluid solution the nHo ligand may rotate freely. The nature of the electronic transitions of Re(CO)3(bpy)(nHo)(+) were established by TD-DFT calculations. The set of the most important electronic transitions present in this complex are comprised of pi->pi* electronic transitions centered on bpy and nHo moieties, LLCTnHo->COs, MLLCTRe(CO)3->bpy and LLCTnHo->bpy transitions. Additionally, TD DFT calculations predict the existence of another two intense MLLCTRe(CO)3->nHo electronic transitions. Calculated UV-vis absorption spectra are in good agreement with the corresponding experimental data for the bpy-containing complex. PMID- 26365708 TI - Helicobacter pylori strains vary cell shape and flagellum number to maintain robust motility in viscous environments. AB - The helical shape of the human stomach pathogen Helicobacter pylori has been suggested to provide mechanical advantage for penetrating the viscous stomach mucus layer. Using single-cell tracking and quantitative morphology analysis, we document marked variation in cell body helical parameters and flagellum number among H. pylori strains leading to distinct and broad speed distributions in broth and viscous gastric mucin media. These distributions reflect both temporal variation in swimming speed and morphologic variation within the population. Isogenic mutants with straight-rod morphology showed 7-21% reduction in speed and a lower fraction of motile bacteria. Mutational perturbation of flagellum number revealed a 19% increase in speed with 4 versus 3 median flagellum number. Resistive force theory modeling incorporating variation of both cell shape and flagellum number predicts qualitative speed differences of 10-30% among strains. However, quantitative comparisons suggest resistive force theory underestimates the influence of cell body shape on speed for helical shaped bacteria. PMID- 26365710 TI - Design, synthesis, and biological evaluation of amide imidazole derivatives as novel metabolic enzyme CYP26A1 inhibitors. AB - All-trans-retinoic acid (ATRA) as a physiological metabolite of vitamin A is widely applied in the treatment of cancer, skin, neurodegenerative and autoimmune diseases. CYP26A1 enzyme, induced by ATRA in liver and target tissues, metabolizes ATRA into 4-hydroxyl-RA. Inhibition of CYP26A1 metabolic enzyme represents a promising strategy for discovery of new specific anticancer agents. Herein, we describe the design, synthesis and biological evaluation of a series of new amide imidazole derivatives as retinoic acid metabolism blocking agents (RAMBAs) toward CYP26A1 enzyme. First, based on the recent theoretical models (Sun et al., J. Mol. Graph. Model., 2015, 56, 10-19) a series of RAMBAs with novel scaffolds were designed using fragment-based drug discovery approach. Subsequently, the new RAMBAs were synthesized and evaluated for their biological activities. All the compounds demonstrated appropriate enzyme activities and cell activities. The promising inhibitors 20 and 23 with IC50 value of 0.22 MUM and 0.46 MUM toward CYP26A1, respectively, were further evaluated for CYP selectivity and the metabolic profile of ATRA. Both compounds 20 and 23 showed higher selectivity for CYP26A1 over other CYPs (CYP2D6, CYP3A4) when compared to liarozole. They also showed better inhibitory activities for the metabolism of ATRA when also compared to liarozole. These studies further validated the pharmacophore and structure-activity relationship models obtained about CYP26A1 inhibitors and highlighted the promising activities of the new series of CYP26A1 inhibitors designed from such models. They also paved the way for future development of those candidates as potential drugs. PMID- 26365711 TI - Comparison of Scheuermann's kyphosis correction by combined anterior-posterior fusion versus posterior-only procedure. AB - INTRODUCTION: Conventional treatment of rigid deformity in Scheuermann's kyphosis (SK) in young patients includes a preliminary anterior spinal release and fusion (ASF) followed by posterior spinal fusion and instrumentation (PSF). However, recently there are more trends to do posterior-only surgery for correction of this deformity. The aim of our study was to compare clinical and radiological outcomes of ASF/PSF and PSF-only procedures in treatment of SK. MATERIALS AND METHODS: In a prospective clinical and radiological review, thirty operated SK patients in two groups were evaluated. Group A: ASF/PSF technique (n: 16) and group B: PSF-only procedure (n: 14) were followed for at least 2 years (average 57.6 months). Two groups were well matched for the following four criteria: average age, flexibility status, posterior fusion levels, and preoperative Cobb's kyphosis angle. Oswestry disability index (ODI) and scoliosis research society questionnaire-30 (SRS-30) and radiological (kyphosis correction, correction loss, sagittal balance) parameters were evaluated before and after surgery and at the final follow-up. RESULTS: In group A, primary thoracic Cobb's kyphosis, immediate post-operative kyphosis, and final follow-up kyphosis angle were 83.6 degrees , 41.4 degrees and 43 degrees , respectively (P < 0.05). Correction rate and correction loss were 50.5 % and 1.6 degrees +/- 2.4, respectively. In group B, the corresponding values were 81.9 degrees , 40.1 degrees and 43.2 degrees , respectively (P < 0.05). Correction rate and correction loss were 51 % and 3.1 degrees +/- 2.5, respectively. SRS-30 and ODI scores in group A were averaged 68.5 and 21.3 preoperatively and 128.7 and 6.25 at the final follow-up, respectively. In group B, the corresponding values were 64 and 23.2 preoperatively and 133.5 and 5.8 at the final follow-up, respectively. CONCLUSIONS: Clinical and radiological parameters were similar in both groups after surgical correction while, complication rates, operation time and blood loss were significantly higher in ASF/PSF procedure. PMID- 26365712 TI - Expressive suppression and neural responsiveness to nonverbal affective cues. AB - Optimal social functioning occasionally requires concealment of one's emotions in order to meet one's immediate goals and environmental demands. However, because emotions serve an important communicative function, their habitual suppression disrupts the flow of social exchanges and, thus, incurs significant interpersonal costs. Evidence is accruing that the disruption in social interactions, linked to habitual expressive suppression use, stems not only from intrapersonal, but also from interpersonal causes, since the suppressors' restricted affective displays reportedly inhibit their interlocutors' emotionally expressive behaviors. However, expressive suppression use is not known to lead to clinically significant social impairments. One explanation may be that over the lifespan, individuals who habitually suppress their emotions come to compensate for their interlocutors' restrained expressive behaviors by developing an increased sensitivity to nonverbal affective cues. To probe this issue, the present study used functional magnetic resonance imaging (fMRI) to scan healthy older women while they viewed silent videos of a male social target displaying nonverbal emotional behavior, together with a brief verbal description of the accompanying context, and then judged the target's affect. As predicted, perceivers who reported greater habitual use of expressive suppression showed increased neural processing of nonverbal affective cues. This effect appeared to be coordinated in a top-down manner via cognitive control. Greater neural processing of nonverbal cues among perceivers who habitually suppress their emotions was linked to increased ventral striatum activity, suggestive of increased reward value/personal relevance ascribed to emotionally expressive nonverbal behaviors. These findings thus provide neural evidence broadly consistent with the hypothesized link between habitual use of expressive suppression and compensatory development of increased responsiveness to nonverbal affective cues, while also suggesting one explanation for the suppressors' poorer cognitive performance in social situations. Moreover, our results point to a potential neural mechanism supporting the development and perpetuation of expressive suppression as an emotion regulation strategy. PMID- 26365713 TI - Achievement of specified lipid and high-sensitivity C-reactive protein levels with two statins in Chinese patients with hypercholesterolaemia. AB - BACKGROUND: Statins reduce plasma low-density lipoprotein cholesterol (LDL-C) and high-sensitivity C-reactive protein (hsCRP) levels. Rosuvastatin 10 mg daily appears to be more potent in reducing LDL-C than simvastatin 40 mg, but the relative effect of these two statin doses on hsCRP is unknown. METHODS: Chinese hyperlipidaemic patients with high cardiovascular risk or familial hypercholesterolaemia (FH) were treated with rosuvastatin 10 mg and simvastatin 40 mg daily in an open-label crossover study. Lipid profiles were measured off treatment and after at least 4 weeks treatment with each of the two statins and hsCRP levels were measured on treatment with both statins. RESULTS: Both treatments were well tolerated in 247 patients (age 55.7 +/- 11.1 years; 100 male; 140 with FH) with good treatment compliance. There were statistically significant differences (P < 0.001) for rosuvastatin versus simvastatin for LDL-C reduction (-52.4 +/- 11.9 % vs. -47.7 +/- 10.8 %) and on-treatment LDL-C (2.62 +/ 0.99 mmol/L vs. 2.86 +/- 0.97 mmol/L), respectively, but the on-treatment hsCRP levels (1.33 +/- 1.37 mg/L vs. 1.41 +/- 1.57 mg/L, P > 0.05) were not significantly different. The lipid target (LDL-C <2.6 mmol/L) was achieved by 52.9 % with rosuvastatin compared with 42.6 % with simvastatin (P < 0.05). The proportions of patients attaining hsCRP targets of < 2 and < 1 mg/L were similar with the two statins (57.1 % and 74.6 % for rosuvastatin vs. 57.1 % and 80.1 % for simvastatin, P > 0.05). CONCLUSION: A significantly greater proportion of patients achieved LDL-C targets with rosuvastatin 10 mg compared to simvastatin 40 mg in Chinese patients with hypercholesterolaemia, but there was no significant difference in achieving hsCRP target levels with the two statins. PMID- 26365714 TI - Sirtuin 4 Regulates Lipopolysaccharide Mediated Leydig Cell Dysfunction. AB - Bacterial lipopolysaccharide (LPS) is the most important contributing factor in pathogenesis of bacterial infection in male accessory glands; and it has shown to inhibit testicular steroidogenesis and induce apoptosis. The present study demonstrates that LPS causes mitochondrial dysfunction via suppression of sirtuin 4 (SIRT4); which in turn affects Leydig cell function by modulating steroidogenesis and apoptosis. LC-540 Leydig cells treated with LPS (10 ug/ml) showed impaired steroidogenesis and increased cellular apoptosis. The mRNA and protein expression of SIRT4 were decreased in LPS treated cells when compared to controls. The obtained data suggest that the c-Jun N-terminal kinase (JNK) activation suppresses SIRT4 expression in LPS treated Leydig cells. Furthermore, the overexpression of SIRT4 prevented LPS induced impaired steroidogenesis and cellular apoptosis by improving mitochondrial function. These findings provide valuable information that SIRT4 regulates LPS mediated Leydig cell dysfunction. PMID- 26365715 TI - Long-term Follow-up of "Simple" Lesions--Atrial Septal Defect, Ventricular Septal Defect, and Coarctation of the Aorta. AB - Surgery for congenital heart disease has advanced significantly in the past 50 years, such that repair of "simple" lesions, such as atrial septal defect, ventricular septal defect, and coarctation of the aorta carries minimal risk, with mortality risk much less than 1%. It was once thought successful repair of these lesions was definitively corrective. There is mounting evidence, however, that there are long-term complications after these repairs, prompting the need for continued follow-up. This review describes the current understanding of diagnosis, treatment, and long-term outcomes for these patients, with the goal of advocating for lifelong surveillance. As the perioperative care of these repairs has evolved significantly over time, so must the way in which we study these patients in the long-term. PMID- 26365716 TI - Anomalous left coronary artery arising from the right pulmonary artery in association with coarctation of the aorta. AB - In this study, we describe a very rare case of anomalous left coronary artery arising from the right pulmonary artery in association with coarctation of the aorta. A 3-month-old boy presented with refractory congestive heart failure since 20 days after birth. The initial echocardiography suggested the diagnosis of left coronary artery-to-right pulmonary artery fistula associated with coarctation; however, selective coronary angiography demonstrated the rare anomaly of the left coronary artery arising from the right pulmonary artery. Subsequently, he underwent successful transcatheter balloon angioplasty for aortic coarctation and surgical repair of left coronary artery re-implantation. PMID- 26365717 TI - Effectiveness of emergency cerclage in cervical insufficiency. AB - OBJECTIVE: To assess the effectiveness of emergency cerclage versus conservative management in improving obstetric and neonatal outcomes in women with clinically evident cervical insufficiency. METHODS: Retrospective cohort study conducted on all women with a single viable pregnancy diagnosed with cervical insufficiency between the 14th and 24th gestational week without pPROM, clinical chorioamnionitis, vaginal bleeding, treatment-resistant uterine contractions or life-incompatible fetal anomalies, from January 2009 to December 2014. Obstetric and neonatal outcomes were compared between women who underwent cerclage and those who refused, preferring a conservative therapy. RESULTS: Eighteen women underwent emergency cerclage and 19 were managed with a conservative therapy. Mean gestational age at delivery, time from diagnosis to delivery and rate of term birth were significantly higher in the first cohort. Those variables show a linear inverse correlation with the degree of cervical dilatation, with better outcomes in patients who underwent cerclage with a dilatation lower than 5.0 cm. No difference in mode of delivery were found. CONCLUSION: Emergency cerclage is a valid therapeutic option between the 14th and 24th gestational week in presence of cervical insufficiency when signs of premature labour or infection are not present, with lower expectations with a dilatation greater than 5 cm. PMID- 26365718 TI - Modulatory effects of inosine, guanosine and uridine on lipopolysaccharide-evoked increase in spike-wave discharge activity in Wistar Albino Glaxo/Rijswijk rats. AB - We showed previously that the number of spike-wave discharges (SWDs) was increased after intraperitoneal (i.p.) injection of lipopolysaccharide (LPS), inosine (Ino) and muscimol alone whereas i.p. guanosine (Guo), uridine (Urd), bicuculline, theophylline and (+)-5-methyl-10,11-dihydro-5H dibenzo(a,d)cyclohepten-5,10-imine maleate (MK-801) alone decreased the SWD number in Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats. These drugs may exert their effects on absence epileptic activity mainly via proinflammatory cytokines evoked increase in cortical excitability (such as LPS), GABAergic system (LPS, Ino, Urd, muscimol and bicuculline), glutamatergic system (LPS, Guo and MK-801) and adenosinergic system (LPS, Ino, Guo, Urd and theophylline). Both GABAergic system and glutamatergic system are involved in the pathomechanism of absence epilepsy, the LPS-evoked increase in absence epileptic activity and the pro- or antiepileptic effects of non-adenosine (non-Ado) nucleosides Ino, Guo and Urd. Moreover, Ino, Guo and Urd have modulatory effects on inflammatory processes. Thus, we investigated whether Ino, Guo and Urd have also modulatory influence on LPS-evoked increase in SWD number using two different concentrations of each nucleoside in WAG/Rij rats. We demonstrated that Ino dose-dependently aggravated whereas Guo and Urd attenuated the LPS-evoked increase in SWD number. Our results suggest that different nucleosides have diverse effects on LPS-induced changes in absence epileptic activity. PMID- 26365719 TI - Direct dynamic nuclear polarization targeting catalytically active (27)Al sites. AB - Here we present a systematic study of direct (27)Al Dynamic Nuclear Polarization (DNP) as induced by three different mono-radical probes with side groups of varying charge states. By employing 4-amino TEMPO that adsorbs to negatively charged surface sites of Al-SBA-15, we achieve a (27)Al signal enhancement factor of ~13 compared to a signal enhancement factor of ~3-4 from mono-radicals that do not adsorb as strongly to the surfaces of Al-SBA-15, here 4-carboxy- and 4 hydroxy-TEMPO. By performing Electron Spin Echo Envelope Modulation (ESEEM) experiments and continuous wave (cw) Electron Paramagnetic Resonance (EPR) lineshape analysis using various nitroxide probes imbibed in Al-SBA-15, we find that direct (27)Al DNP enhancements achieved with different spin probes can be attributed to proximity and local concentration of the spin probes to aluminum on the surface of mesoporous alumina-silica. PMID- 26365720 TI - Outcomes of 13 ICSI-PGD cycles with ejaculated spermatozoa in patients with Klinefelter syndrome. PMID- 26365721 TI - Paraoxonase and arylesterase activities in adults with vitamin B12 deficiency. AB - OBJECTIVE: The purpose of this study was to investigate paraoxonase (PON) and arylesterase (ARES) enzyme activity in adults with vitamin B12 deficiency, and specific changes in the activities of these enzymes following vitamin B12 treatment. METHODS: A total of 46 patients with vitamin B12 deficiency (aged 18 82 years) and 45 healthy volunteer controls (aged 19-64 years) participated in this study. Venous blood samples were collected, and serum vitamin B12, homocysteine (HCY), methylmalonic acid, PON1, and ARES levels were measured. RESULTS: Paired comparison showed that pre- and post-treatment values for PON and ARES were similar between patients and controls (both P > 0.05). There was no statistically significant relationship between patients' pre-/post-treatment PON or HCY levels and serum vitamin B12 levels, compared with those of the control group (P > 0.05). DISCUSSION: The results of the present study do not support the hypothesis that the antioxidant enzymes PON and ARES have an underlying role in vitamin B12 deficiency and related hyperhomocysteinemia. Our findings suggest that PON and ARES do not play a role in the systemic effects of vitamin B12 deficiency. PMID- 26365722 TI - A dendritic beta-galactosidase-responsive folate-monomethylauristatin E conjugate. AB - We report the study of a new drug delivery system programmed for the selective internalisation and the subsequent enzyme-catalysed release of two monomethylauristatin E molecules inside FR-positive cancer cells. This targeting device is the most potent beta-galactosidase-responsive folate-drug conjugate developed so far, killing cancer cells expressing a medium level of FR at low nanomolar concentrations. PMID- 26365723 TI - Strong deshielding in aromatic isoxazolines. AB - Very strong proton deshielding was found in di/tri-aromatic isoxazoline regioisomers prepared from acridin-4-yl dipolarophiles and stable benzonitrile oxides (BNO). Three alkenes, (acridin-4-yl)-CH=CH-R (R = COOCH3, Ph, and CONH2), reacted with three BNO dipoles (2,4,6-trimethoxy, 2,4,6-trimethyl, 2,6-dichloro) to give pairs of target isoxazolines with acridine bound to C-4 or C-5 carbon of the isoxazoline (denoted as 4-Acr or 5-Acr). Regioselectivity was dependent on both the dipolarophile and dipole character. The ester and amide dipolarophile displayed variable regioselectivity in cycloadditions whereas the styrene one afforded prevailing 4-Acr regioisomers. 2,4,6-Trimethoxy-BNO was most prone to form 5-Acr isoxazolines while mesitonitrile oxide gave major 4-Acr isoxazolines. Basic hydrolysis of the amide cycloadduct led to an unexpected isoxazolone product. The structure of the target compounds was studied by NMR, MS, and X-ray crystallography. PMID- 26365724 TI - [Update in Infectious Diseases 2015]. AB - Infectious disease remains current worldwide. During the second half of 2014 an outbreak of ebolavirus hit West Africa with implications in the rest of the world. In fact, Spain declared the first imported case of this infection. Multiresistant enterobacteria outbreaks are emerging all around the world in a moment on which WHO draws attention to the limited resources, coining the term "post antibiotic era". On the other hand, 2014 went down in history as one in which hepatitis C is cured. Are also current HIV epidemiological control or strategies for antiviral and antifungal prophylaxis in immunocompromised hosts. PMID- 26365725 TI - [Applicability of new diagnostic techniques in microbiology; technological innovation]. AB - Different new techniques have been introduced in microbiology laboratories during the last years, including mass spectrometry and next generation sequencing. These techniques, in addition to automation, microfludics, nanotechnology and informatics, have impelled innovation in the prevention and management of patients with infectious diseases. These approaches are relevant for revitalization and consolidation Clinical Microbiology laboratories. PMID- 26365726 TI - [Laboratory detection of carbapenemase-producing Enterobacteriaceae]. AB - Detection of carbapenemase-producing Enterobacteriaceae in the laboratory requires an exhaustive analysis of the antibiogram and susceptibility to all beta lactams, the implementation with phenotypic methods of screening as well as confirmatory procedures including the detection of the carbapenem hydrolysis, the inhibition of the enzyme activity with several specific inhibitor compounds and by molecular methods. PMID- 26365727 TI - [Therapeutic options for carbapenemase-producing Enterobacteriaceae]. AB - Carbapenemase-producing Enterobacteriaceae (CPE) has spread worldwide becoming a threat to public health. However, no randomized clinical trials about the efficacy of optimizing antibiotic treatment have been published. Experimental studies have been designed to find combinations of antibiotics with synergistic activity. Their main aim has been increasing the speed of bacterial destruction and decreasing resistance. The latest guidelines recommend combination therapy. The carbapenems has been chosen as the basis of such therapy. We face limited therapeutic options. Polymyxins, fosfomycin and gentamicin have reemerged in this context, becoming the basis of multiple combination regimens, with beneficial effects both in vitro and in murine models of infection. PMID- 26365728 TI - [Usefulness of PK/PD parameters of antimicrobials in the treatment of complex and extremely-resistant infections]. AB - Complex or difficult to treat infections should benefit from antimicrobial PK/PD data in each specific situation. In the case of multidrug resistant gram negative infections the optimized use of colistin needs the using of PK/PD indexes. Likewise, in infections of inaccessible sources, PK/PD concepts play a key role in choosing the best antimicrobial and dosage. An example would be the potential role of linezolid in CNS infections. Among fungal infections, symptomatic candiduria by fluconazole-resistant strains are a therapeutic challenge. In this context micafungin could be a good alternative, again based on PK/PD concepts. PMID- 26365729 TI - [Inhaled medication and inhalation devices for lung disease]. AB - Nebulized antibiotic therapy is an attractive therapeutic option given the high concentration obtained from the drug at the site of infection, minimizing the adverse effects and possible drug interactions. Inhalation of drugs as treatment of cystic fibrosis (CF) related lung disease has been proven to be highly effective. Consequently, an increasing number of drugs and devices have been developed for CF lung disease or are currently under development. Other limited areas of experience in this field are lung transplant recipients, immunosuppressed patients, bronchiectasis and ventilated patients. In this review document we analyse the current status of the inhaled medications, their modes of administration and indications and their results as well as side effects. Specifically we address antibiotics, and additionally, we review the current knowledge on devices for inhalation therapy with regard to optimal particle sizes and characteristics of wet nebulisers, dry powder and metered dose inhalers. Several factors contribute to a highly variable pulmonary drug deposition as the devices, the physical properties of the administered antimicrobial agent, the type of respiratory disease and the inhalation technique. Despite many clinicians have obtained a valuable experience from the aerosolized administration of antimicrobials and persuaded of their efficacy and safety. However, RCTs out of CF are needed to answer important clinical questions, such as what is the appropriate dose, the optimal delivery device, the optimal way of drug administration, as well as the exact therapeutic role and pharmacokinetic profile of aerosolized drug. PMID- 26365730 TI - [Cloxacillin-susceptible Staphylococcus aureus with high MIC to glycopeptides. Ever we use cloxacillin?]. AB - Staphylococcus aureus infections are yet an important cause of morbidity and mortality despite of numerous effective anti-staphylococcal antibiotics available. There has been an increasing incidence of methicillin-resistant strains which might have led to a wider use of vancomycin. This seems to ride alongside a covert progressive increase of S. aureus vancomycin minimum inhibitory concentration. In this way, the emergence of vancomycin-intermediate S. aureus (VISA) strains and heteroresistant-VISA has raised concern for the scarcity of alternative treatment options. Equally alarming, though fortunately less frequent, is the emergence of vancomycin-resistant S. aureus. Ultimately, various debate issues have arisen regarding the emergence of S. aureus strains with decreased vancomycin susceptibility, within the range still considered sensitive. These strains have shown a different clinical behaviour regardless of vancomycin use, both in methicillin resistant and sensitive S. aureus. The emergence of increasing vancomycin-resistance in S. aureus isolates, has stirred up the basis of therapeutic approach in staphylococcal infections. There is yet much to explore to better define the impact of higher vancomycin minimum inhibitory concentration in staphylococcal infections. PMID- 26365731 TI - [Duration of antimicrobial therapy]. AB - The management of infectious diseases is always complex, not only because of its high incidence and mortality, but the difficulty of designing effective treatments that minimize the development of bacterial resistance in the clinical setting. One of the most important options is the reduction of exposure to antibiotic treatment, optimizing by desescalation and shortening the duration of therapy. PMID- 26365732 TI - [Management of invasive candidiasis in non-neutropenic patient]. AB - Among the most frequents etiological agents that causing nosocomial infections, there is included Candida spp. Candida's bloodstream infection mortality rates are over 30%. Antifungal early treatment is essential to improve the prognosis of this type of infection. Because of the lack of fast enough microbiological tests for early diagnosis, treatment must necessarily be initiated empirically. PMID- 26365733 TI - [Filamentous fungal infections in immunosuppressed patients: prophylaxis and treatment]. AB - Although the incidence of invasive aspergillosis has decreased in haematologic patients and solid organ transplant recipients due to the use of prophylaxis; aspergillosis has emerged in other populations undergoing immunosuppressive drugs where prophylaxis is not well defined presenting different clinical patterns. Voriconazole is the gold standard in the treatment of aspergillosis and probably combined therapy, with voriconazole plus anidulafungin, could have a role in the initial management of the infection. PMID- 26365734 TI - [Update on Ebola virus infection]. AB - Ebola virus disease became a major global public health concern after the last outbreak originated in West Africa in 2014. The epidemic has affected 10 countries in 3 continents, with an estimated global mortality of 41%, highlighting how a disease known to be restricted to the African continent can affect directly or indirectly many countries in the world. In this work, we review different aspects of the virus, the disease and the current outbreak. PMID- 26365735 TI - [Therapeutic update in hepatitis C]. AB - Hepatitis C virus infection is a major health burden affecting 130-170 million people worldwide. Approximately 10-30% of those with chronic hepatitis C will progress to cirrhosis over 20-30 years. The development of new direct-acting antivirals has changed the management of the disease, allowing efficacious Interferon-free therapies superior to prior treatment regimens with minimal side effects, even in some subgroups previously thought to be difficult to cure such as cirrhotic patients. PMID- 26365736 TI - [Optimization strategies in management of CMV infection in transplant patients]. AB - Currently, two therapeutic strategies are applied for preventing the development of CMV end-organ disease in transplant recipients: universal prophylaxis and preemptive antiviral therapy. Both are potentially optimable. As for the former strategy, precisely identifying patients at greatest risk of viremia would allow for a targeted prophylaxis. In this sense several genotypic, immunological and biological markers have been described that could be ancillary to that purpose. As for the latter strategy, combined monitoring of plasma CMV DNA load and peripheral levels of CMV-specific CD8 + and CD4 + IFN-gamma producing T cells would permit a more rationale use of antivirals, thus avoiding overtreatment and derived toxicity. PMID- 26365737 TI - [Is it possible to cure HIV infection?]. AB - Antiretroviral therapy has significantly improved the life expectancy in HIV infected people, but it cannot cure the disease by itself. Several barriers have been identified for the cure of HIV infection, including a reservoir of latently infected cells, persistent viral replication in tissues, and anatomical sanctuaries. The main strategy proposed for the cure of HIV consists on the administration of drugs that, through the reactivation of latent HIV, would eliminate the cell reservoir. Ongoing clinical trials have shown the proof of concept, but the efficacy of these drugs in decreasing the reservoir size has not been proved so far. PMID- 26365738 TI - Carbonic anhydrase generates a pH gradient in Bombyx mori silk glands. AB - Silk is a protein of interest to both biological and industrial sciences. The silkworm, Bombyx mori, forms this protein into strong threads starting from soluble silk proteins using a number of biochemical and physical cues to allow the transition from liquid to fibrous silk. A pH gradient has been measured along the gland, but the methodology employed was not able to precisely determine the pH at specific regions of interest in the silk gland. Furthermore, the physiological mechanisms responsible for the generation of this pH gradient are unknown. In this study, concentric ion selective microelectrodes were used to determine the luminal pH of B. mori silk glands. A gradient from pH 8.2 to 7.2 was measured in the posterior silk gland, with a pH 7 throughout the middle silk gland, and a gradient from pH 6.8 to 6.2 in the beginning of the anterior silk gland where silk processing into fibers occurs. The small diameter of the most anterior region of the anterior silk gland prevented microelectrode access in this region. Using a histochemical method, the presence of active carbonic anhydrase was identified in the funnel and anterior silk gland of fifth instar larvae. The observed pH gradient collapsed upon addition of the carbonic anhydrase inhibitor methazolamide, confirming an essential role for this enzyme in pH regulation in the B. mori silk gland. Plastic embedding of whole silk glands allowed clear visualization of the morphology, including the identification of four distinct epithelial cell types in the gland and allowed correlations between silk gland morphology and silk stages of assembly related to the pH gradient. B. mori silk glands have four different epithelial cell types, one of which produces carbonic anhydrase. Carbonic anhydrase is necessary for the mechanism that generates an intraluminal pH gradient, which likely regulates the assembly of silk proteins and then the formation of fibers from soluble silk proteins. These new insights into native silk formation may lead to a more efficient production of artificial or regenerated silkworm silk fibers. PMID- 26365739 TI - A reference gene set for chemosensory receptor genes of Manduca sexta. AB - The order of Lepidoptera has historically been crucial for chemosensory research, with many important advances coming from the analysis of species like Bombyx mori or the tobacco hornworm, Manduca sexta. Specifically M. sexta has long been a major model species in the field, especially regarding the importance of olfaction in an ecological context, mainly the interaction with its host plants. In recent years transcriptomic data has led to the discovery of members of all major chemosensory receptor families in the species, but the data was fragmentary and incomplete. Here we present the analysis of the newly available high-quality genome data for the species, supplemented by additional transcriptome data to generate a high quality reference gene set for the three major chemosensory receptor gene families, the gustatory (GR), olfactory (OR) and antennal ionotropic receptors (IR). Coupled with gene expression analysis our approach allows association of specific receptor types and behaviors, like pheromone and host detection. The dataset will provide valuable support for future analysis of these essential chemosensory modalities in this species and in Lepidoptera in general. PMID- 26365740 TI - Efficacy and Complications of Palliative Irradiation in Three Scottish Fold Cats with Osteochondrodysplasia. PMID- 26365743 TI - Intracellular zinc in insulin secretion and action: a determinant of diabetes risk? AB - Zinc is an important micronutrient, essential in the diet to avoid a variety of conditions associated with malnutrition such as diarrhoea and alopecia. Lowered circulating levels of zinc are also found in diabetes mellitus, a condition which affects one in twelve of the adult population and whose treatments consume approximately 10 % of healthcare budgets. Zn2+ ions are essential for a huge range of cellular functions and, in the specialised pancreatic beta-cell, for the storage of insulin within the secretory granule. Correspondingly, genetic variants in the SLC30A8 gene, which encodes the diabetes-associated granule resident Zn2+ transporter ZnT8, are associated with an altered risk of type 2 diabetes. Here, we focus on (i) recent advances in measuring free zinc concentrations dynamically in subcellular compartments, and (ii) studies dissecting the role of intracellular zinc in the control of glucose homeostasis in vitro and in vivo. We discuss the effects on insulin secretion and action of deleting or over-expressing Slc30a8 highly selectively in the pancreatic beta cell, and the role of zinc in insulin signalling. While modulated by genetic variability, healthy levels of dietary zinc, and hence normal cellular zinc homeostasis, are likely to play an important role in the proper release and action of insulin to maintain glucose homeostasis and lower diabetes risk. PMID- 26365742 TI - Variability in recording and scoring of respiratory events during sleep in Europe: a need for uniform standards. AB - Uniform standards for the recording and scoring of respiratory events during sleep are lacking in Europe, although many centres follow the published recommendations of the American Academy of Sleep Medicine. The aim of this study was to assess the practice for the diagnosis of sleep-disordered breathing throughout Europe. A specially developed questionnaire was sent to representatives of the 31 national sleep societies in the Assembly of National Sleep Societies of the European Sleep Research Society, and a total of 29 countries completed the questionnaire. Polysomnography was considered the primary diagnostic method for sleep apnea diagnosis in 10 (34.5%), whereas polygraphy was used primarily in six (20.7%) European countries. In the remaining 13 countries (44.8%), no preferred methodology was used. Fifteen countries (51.7%) had developed some type of national uniform standards, but these standards varied significantly in terms of scoring criteria, device specifications and quality assurance procedures between countries. Only five countries (17.2%) had published these standards. Most respondents supported the development of uniform recording and scoring criteria for Europe, which might be based partly on the existing American Academy of Sleep Medicine rules, but also take into account differences in European practice when compared to North America. This survey highlights the current varying approaches to the assessment of patients with sleep-disordered breathing throughout Europe and supports the need for the development of practice parameters in the assessment of such patients that would be suited to European clinical practice. PMID- 26365744 TI - Final diagnosis of children and adolescents with musculoskeletal complaints. AB - BACKGROUND: Musculoskeletal complaints (MSCs) are one of the leading causes of outpatient admissions. However, analytical and epidemiological data are limited. The aim of this study is to identify the etiology of MSCs (excluding acute traumatic conditions) in children and adolescents, and to identify clues for the differential diagnosis. METHODS: Children and adolescents presenting with musculoskeletal pain, swelling or limitation of movement were enrolled in a prospective design. Demographic, clinical and laboratory features were recorded. RESULTS: Four hundred and twenty-two children (48.2% female) with a mean age of 7.90+/-3.95 years were enrolled. Etiology was identified in 97.2% of the cases: non-inflammatory and mechanical conditions (NIMC; 42.2%), rheumatic diseases (RD; 31%), infection-related disorders (IRD; 21.6%) and malignancy (M; 2.4%). NIMC was characterized by longer duration of complaints, a higher rate of non-articular complaints, a lower rate of joint involvement and limping and lower levels of leukocytes, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). The prevalence of RD was higher in the age group of >12 years; younger age was associated with higher prevalence of IRD. Small-joint involvement was highest in the RD group. Median ESR in RD and M groups was higher; compared to the other groups; the frequency of patients with ESR >= 60 mm/hr was higher in the M group; compared to the RD group. In the RD group familial Mediterranean fever (9.7%), juvenile idiopathic arthritis (8.3%) and Henoch-Schonlein purpura (5.7%) were the leading causes of MSCs. CONCLUSIONS: RD accounted for one-third of the etiologies for MSCs. Age, duration of complaints, pattern of joint involvement and acute phase reactants are practical tools that may guide the pediatrician for diagnosis. PMID- 26365745 TI - Predictive risk factors for relapse after cessation of inhaled corticosteroids in well-controlled childhood asthma. AB - BACKGROUND: There is limited data for predicting the risk of exacerbations following the cessation of inhaled corticosteroids (ICS) in well controlled childhood asthma. In current study, clinical, functional and inflammatory parameters at the time of ICS withdrawal were investigated in that respect. METHODS: Forty children asymptomatic for at least 3 months on low dose ICS's were enrolled and ICS were discontinued in summer. At enrolment symptom/medication diary, pulmonary function parameters, methacholine provocation testing, peripheral blood eosinophilia, serum total and allergen-specific IgE levels and skin prick testing were performed. In a subgroup of patients, phytohemaglutinin induced secretion of IL-5, IL-13, IFN-gamma and IL-10 from blood mononuclear cells were measured. Patients were assessed with symptom/medication diary and pulmonary function test every 2 months for 6 months. RESULTS: Eighteen of 37 patients experienced recurrence of acute asthma symptoms. In patients with acute attack (group I), changes in rhinitis symptom scores at 2nd month vs. baseline were statistically higher. In addition, group I had significantly higher rhinitis symptom scores compared to group II at fourth-month visit. Patients with acute exacerbation revealed a significant decrease in FEV1% at 2nd month compared to baseline. Moreover, group I showed significantly lower FEF 25-75% compared to group II at 2nd month. Baseline bronchial hyper-responsiveness with methacholine was found to be an independent risk factor for asthma exacerbation. CONCLUSIONS: The findings of this study identified baseline bronchial hyperreactivity, higher rhinitis symptom scores and gradual decrease in pulmonary function parameters during follow-up as risk factors for subsequent exacerbation of asthma. PMID- 26365746 TI - Swallowing dysfunction as a factor that should be remembered in recurrent pneumonia: videofluoroscopic swallow study. AB - BACKGROUND: The swallow function is one of the strong defense mechanism against aspiration. Aspiration and pneumonia are unavoidable in patients with defective mechanism of swallowing. The aim of this study was to evaluate patients with recurrent pneumonia in terms of videofluoroscopic examination results. METHODS: The study comprised fifty pediatric cases (22 boys, 28 girls) with an average age of 2.9 years (2 months-7.5 years) who were referred to our clinic due to suffering from recurrent pneumonia. The videofluoroscopic swallow study (VFSS) was performed on all patients. The presence of a correlation with pneumonia was investigated. RESULTS: In 45 of the children, VFSS results were not normal. Of the children, 41 had mental-motor retardation. The results of the videofluoroscopic study show that silent aspiration was the most common pathology in participants with the percentage of 40 (27.5% mild, 17.5% severe). Patients in the study had pneumonia with an incidence of 2.6 illnesses per year. Having one than more results on VFSS was found to be associated with more number of annual pneumonia episodes. CONCLUSIONS: Children with neurological impairments are at risk of recurrent acute pneumonia due to aspiration. Disturbances of swallowing phases should be remembered as a cause of pneumonia in these patients. PMID- 26365747 TI - Development of a new fetal growth curve from a large sample of Italian population. AB - BACKGROUND: Intrauterine growth curves are considered an essential instrument in prenatal medicine for an appropriate auxological classification of fetuses and they have a great importance in clinical practice. Nowadays, in Italy a national curve published in 1975, is the most used. It Is based on birth weights of 8458 newborns from physiological pregnancies. The aim of the present study was to develop a modern fetal growth curve based on accurately selection of 35 240 physiological singleton Italian pregnancies with sure gestational age confirmed by ultrasound. METHODS: This is a retrospective analysis of 35,240 pregnancies from "A. Gemelli" University Hospital in Rome and "S. Anna" University Hospital in Turin from January 2001 to December 2006. Non-resident pregnant women or coming from other countries, women with diabetes, hypertensive disorders of pregnancy, multiple pregnancies, fetuses with major malformations and/or chromosomal disorders and stillborn fetuses were excluded. RESULTS: An increasing trend of median neonatal weight, in comparison with the previous Italian National Curve drawn up in 1975, was found. CONCLUSIONS: Combining data from two centers, a new fetal growth curve, in which the 10th and the 90th percentiles are clinically reliable, was performed, in order to have a better tool to evaluate the Italian fetal population. A trend towards an increase of birth weight was observed if compared to previous growth curve drawn up more than 30 years ago. PMID- 26365748 TI - Use of LigaSureTM on bile duct in rats: an experimental study. AB - BACKGROUND: The closure of a cystic duct during cholecystectomy by means of radiofrequency is still controversial. We report our preliminary experimental results with the use of LigaSureTM on common bile duct in rats. METHODS: Thirty Wistar rats weighing 70 to 120 g were employed for this study. The animals were all anesthetized with intraperitoneal ketamine and then divided into three groups. The first group (10 rats, Group C) underwent only laparotomy and isolation of the common bile duct. The second (10 rats, Group M) underwent laparotomy and closure of the common bile duct (CBD) with monopolar coagulation. The third group (10 rats, Group L) underwent laparotomy and sealing of the common bile duct with two application of LigaSureTM. Afterwards, all rats were kept in comfortable cages and were administered dibenzamine for five days. They were all sacrificed on day 20. Through a laparotomy, the liver and bile duct were removed for histological examination. Blood samples were obtained to dose bilirubin, amylase and transaminase levels. RESULTS: Mortality rate was 0 in the control group (C), 3/10 rats in group M and 0 in group L. In group L, the macroscopic examination showed a large choledochocele (3-3.5 * 1.5 cm) with few adhesions. At the histological examination there was optimal sealing of the common bile duct in 9/10 rats. In group M, 2/10 rats had liver abscesses, 3/10 rats had choledochocele and 5/10 rats, biliary peritonitis. There was intense tissue inflammation and the dissection was difficult. Analyses of blood samples showed an increase in total bilirubin, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in groups M and L. CONCLUSIONS: The preliminary results of our study confirm that radiofrequency can be safely used for the closure of the common bile duct. The choledochocele obtained with this technique could represent a good experimental model. These results could be a further step for using the LigaSureTM in clipless cholecystectomy. PMID- 26365749 TI - [Idiopathic Nephrotic Syndrome: recommendations of the Nephrology Branch of the Chilean Society of Pediatrics. Part two]. AB - Idiopathic nephrotic syndrome is the most common glomerular disease in childhood, affecting 1 to 3 per 100,000 children under the age of 16. It most commonly occurs in ages between 2 and 10. Its cause is unknown, and its histology corresponds to minimal change disease in 90% of cases, or focal segmental glomerulosclerosis. Steroid-resistant nephrotic syndrome represents 10-20% of idiopathic nephrotic syndrome in pediatrics. It has a poor prognosis, and its management is a significant therapeutic challenge. Half of patients evolve to end stage renal disease within 5 years, and are additionally exposed to complications secondary to persistent NS and to the adverse effects of immunosuppressive therapy. The primary goal of treatment is to achieve complete remission, but even a partial remission is associated with a better renal survival than the lack of response. This paper is the result of the collaborative effort of the Nephrology Branch of the Chilean Society of Pediatrics with aims at helping pediatricians and pediatric nephrologists to treat pediatric idiopathic nephrotic syndrome. In this second part, handling of steroid-resistant nephrotic syndrome as well as nonspecific therapies are discussed. PMID- 26365750 TI - [Successful endovascular treatment of thoracic aortic aneurysm secondary to infection of the umbilical artery catheter in preterm infants]. AB - Aortic aneurysms (AA) in the paediatric population are uncommon. The use of umbilical catheters in neonates has been associated with infections and, on some occasions, the formation of aortic aneurysms. The surgical repair of these aneurysms is one type of treatment; however, percutaneous intervention with stents could provide an alternative treatment route, with fewer complications. The aim of this report is to present the therapeutic scope of a hybrid procedure, in which the combined surgical and percutaneous technique offers a less invasive alternative to open surgery for the repair of aortic aneurysms or their main branches. CLINICAL CASE: The case concerns a pre-term newborn of 30 weeks weighing 1,335 g. An umbilical catheter was introduced, which was withdrawn at 14 days due to an infection. It developed as Staphylococcus aureus with sepsis. The echocardiogram and Angio-CT confirmed AA, which were managed using a hybrid procedure of surgery and the endovascular implantation of 2 coated stents (Atrium V12 XR Medical Corp, Hudson, NH). The post-procedure clinical follow-ups, including abdominal echo-tomography, confirmed the success of the treatment. CONCLUSION: The endovascular aortic aneurysm repair procedure in premature newborns may be considered when deciding treatment of this disease, and could avoid the risks associated with open surgery. However, follow-up and monitoring is required while the patient grows up, due to the possibility that the implanted stents require re-dilating. The outcomes of neonatal endovascular procedures in the future are unknown. PMID- 26365752 TI - Pyrrolizidine and tropane alkaloids in teas and the herbal teas peppermint, rooibos and chamomile in the Israeli market. AB - Dehydro pyrrolizidine alkaloids (dehydro PAs) are carcinogenic phytotoxins prevalent in the Boraginaceae, Asteraceae and Fabaceae families. Dehydro PAs enter the food and feed chain by co-harvesting of crops intended for human and animal consumption as well as by carry-over into animal-based products such as milk, eggs and honey. Recently the occurrence of dehydro PAs in teas and herbal teas has gained increasing attention from the EU, due to the high levels of dehydro PAs found in commercially available teas and herbal teas in Germany and Switzerland. Furthermore, several tropane alkaloids (TAs, e.g. scopolamine and hyoscyamine) intoxications due to the consumption of contaminated herbal teas were reported in the literature. The aim of the present study was to determine the dehydro PAs and TAs levels in 70 pre-packed teabags of herbal and non-herbal tea types sold in supermarkets in Israel. Chamomile, peppermint and rooibos teas contained high dehydro PAs levels in almost all samples analysed. Lower amounts were detected in black and green teas, while no dehydro PAs were found in fennel and melissa herbal teas. Total dehydro PAs concentrations in chamomile, peppermint and rooibos teas ranged from 20 to 1729 MUg/kg. Except for black tea containing only mono-ester retrorsine-type dehydro PAs, all other teas and herbal teas showed mixed patterns of dehydro PA ester types, indicating a contamination by various weed species during harvesting and/or production. The TA levels per teabag were below the recommended acute reference dose; however, the positive findings of TAs in all peppermint tea samples warrant a more extensive survey. The partially high levels of dehydro PAs found in teas and herbal teas present an urgent warning letter to the regulatory authorities to perform routine quality control analysis and implement maximum residual levels for dehydro PAs. PMID- 26365751 TI - Predicting Cerebral Hyperperfusion Syndrome Following Superficial Temporal Artery to Middle Cerebral Artery Bypass based on Intraoperative Perfusion-Weighted Magnetic Resonance Imaging. AB - Moyamoya disease leads to the formation of stenosis in the cerebrovasculature. A superficial temporal artery to middle cerebral artery (STA-MCA) bypass is an effective treatment for the disease, yet it is usually associated with postoperative cerebral hyperperfusion syndrome (CHS). This study aimed to evaluate cerebral hemodynamic changes immediately after surgery and assess whether a semiquantitative analysis of an intraoperative magnetic resonance perfusion-weighted image (PWI) is useful for predicting postoperative CHS. Fourteen patients who underwent the STA-MCA bypass surgery were included in this study. An atlas-based registration method was employed for studying hemodynamics in different cerebral regions. Pre- versus intraoperative and group-wise comparisons were conducted to evaluate the hemodynamic changes. A postoperative increase in relative cerebral blood flow (CBF) at the terminal MCA territory (P = 0.035) and drop in relative mean-time-transit at the central MCA territory (P = 0.012) were observed in all patients. However, a significant raise in the increasing ratio of relative-CBF at the terminal MCA territory was only found in CHS patients (P = 0.023). The cerebrovascular changes of the patients after revascularization treatment were confirmed. Intraoperative PWI might be helpful in predicting the change in relative-CBF at MCA terminal territory which might indicate a risk of CHS. PMID- 26365753 TI - Depinning Transition of a Domain Wall in Ferromagnetic Films. AB - We report first principle numerical study of domain wall (DW) depinning in two dimensional magnetic film, which is modeled by 2D random-field Ising system with the dipole-dipole interaction. We observe nonconventional activation-type motion of DW and reveal the fractal structure of DW near the depinning transition. We determine scaling functions describing critical dynamics near the transition and obtain universal exponents establishing connection between thermal softening of pinning potential and critical dynamics. We observe that tuning the strength of the dipole-dipole interaction switches DW dynamics between two different universality classes, corresponding to two distinct dynamic regimes characterized by non-Arrhenius and conventional Arrhenius-type DW motions. PMID- 26365754 TI - Laser light routing in an elongated micromachined vapor cell with diffraction gratings for atomic clock applications. AB - This paper reports on an original architecture of microfabricated alkali vapor cell designed for miniature atomic clocks. The cell combines diffraction gratings with anisotropically etched single-crystalline silicon sidewalls to route a normally-incident beam in a cavity oriented along the substrate plane. Gratings have been specifically designed to diffract circularly polarized light in the first order, the latter having an angle of diffraction matching the (111) sidewalls orientation. Then, the length of the cavity where light interacts with alkali atoms can be extended. We demonstrate that a longer cell allows to reduce the beam diameter, while preserving the clock performances. As the cavity depth and the beam diameter are reduced, collimation can be performed in a tighter space. This solution relaxes the constraints on the device packaging and is suitable for wafer-level assembly. Several cells have been fabricated and characterized in a clock setup using coherent population trapping spectroscopy. The measured signals exhibit null power linewidths down to 2.23 kHz and high transmission contrasts up to 17%. A high contrast-to-linewidth ratio is found at a linewidth of 4.17 kHz and a contrast of 5.2% in a 7-mm-long cell despite a beam diameter reduced to 600 MUm. PMID- 26365755 TI - Predicting recurrence after curative resection for gastric cancer: External validation of the Italian Research Group for Gastric Cancer (GIRCG) prognostic scoring system. AB - BACKGROUND: Most nomograms for Gastric Cancer (GC) were developed to predict overall survival (OS) after curative resection. The Italian Research Group for Gastric Cancer (GIRCG) prognostic scoring system (PSS) was designed to predict the recurrence risk after curative treatment based on pathologic tumor stage and treatment performed (D1-D2/D3 lymphadenectomy). This study was carried out to externally validate the GIRCG's PSS. PATIENTS AND METHODS: Adopting the same criteria used by GIRCG to build the PSS, 185 patients with GC operated with curative intention were selected. The median follow-up period was 77.8 months (1.93-150.8) for all patients and 102.5 months (60.9-150.8) for patients free of disease. The NRI (net reclassification improvement) was calculated to estimate the overall improvement in the reclassification of patients using the PSS in place of the TNM stage system. RESULTS: GC recurrence occurred in 70 (37.8%) patients. The mean time to recurrence was 22.2 (range 1.9-98.1) months. For patients with recurrence, the gain in the proportion of reclassification was 0.257 (p < 0.001), indicating an improvement of 26%. For patients without recurrence, the gain in the proportion of reclassification was -0.122 (p < 0.001), indicating a worsening of 12%. The NRI calculated was 0.135 (p = 0.0527). CONCLUSION: The GIRCG's PSS, which predicts the likelihood of recurrence after radical surgical treatment for GC, is more accurate than TNM system to predict recurrence mainly for high-risk patients. Yet, the PSS does not have the same effectiveness for low-risk patients, overestimating the chance of recurrence occurs even for disease-free patients. PMID- 26365756 TI - Neourethral meatus reconstruction for vulvectomies requiring resection of the distal part of the urethra. AB - OBJECTIVE: Vulvar cancer is a relatively rare tumour accounting for just 5% of all gynaecological malignancies. Radical excision can sometimes involve the distal one-third to one-half of the urethra leading to postoperative problems with micturition, asymmetries and psychosexual distress. Although this topic has been largely addressed, no specific method for distal urethra reconstruction has been described. The aim of this paper is to assess the safety and reliability of our reconstructive technique. METHODS: We conducted a retrospective study of 47 consecutive patients who underwent neourethral meatus reconstruction with vaginal mucosa flap. The surgical technique is described step-by-step. We reviewed the patients' demographics, operative characteristics, as well as immediate complications and long-term outcomes. RESULTS: Neo-meatal reconstruction was combined to direct vulvar closure in 2 patients, rhomboid flaps in 3 cases, 1 bilateral lotus flap and 36 V-Y fasciocutaneous flaps, 4 rectus abdominis and 1 gracilis flap. Wound dehiscence at the site of the neourethral reconstruction occurred in only 4.3%, partial necrosis of the vaginal mucosa flap in 2.1%. Totally post-operative early complication rate including the whole procedures was 29.8% with a re-operation rate of 4.3%. Long-term outcomes were evaluated in 68.1% patients, including 18.7% of urinary incontinence, no urethral stenosis and 25% of narrowed vaginal introitus. CONCLUSION: Neourethral meatus reconstruction using the vaginal mucosa flap is a simple, safe and reliable technique with a very low early complication rate. We suggest that this flap could be a good option to preserve and restore urinary function in case of distal urethral amputation. PMID- 26365757 TI - Adiposity and risk of thyroid cancer: a systematic review and meta-analysis. AB - Thyroid cancer incidence has increased rapidly over time, as has obesity prevalence. A link between the two appears plausible, but the relation of adiposity to thyroid cancer remains incompletely understood. We performed a meta analysis of adiposity measures and thyroid cancer using studies identified through October 2014. Twenty-one articles yielded data on 12,199 thyroid cancer cases. We found a statistically significant 25% greater risk of thyroid cancer in overweight individuals and a 55% greater thyroid cancer risk in obese individuals as compared with their normal-weight peers. Each 5-unit increase in body mass index (BMI), 5 kg increase in weight, 5 cm increase in waist or hip circumference and 0.1-unit increase in waist-to-hip ratio were associated with 30%, 5%, 5% and 14% greater risks of thyroid cancer, respectively. When evaluated by histologic type, obesity was significantly positively related to papillary, follicular and anaplastic thyroid cancers, whereas it revealed an inverse association with medullary thyroid cancer. Both general and abdominal adiposity are positively associated with thyroid cancer. However, relations with BMI vary importantly by tumour histologic type. PMID- 26365758 TI - Rhinitis in pregnant women with asthma is associated with poorer asthma control and quality of life. AB - OBJECTIVE: To describe the pattern and severity of rhinitis in pregnancy and the impact rhinitis has on asthma control and quality of life (QoL) in pregnant women with asthma. METHODS: Two hundred and eighteen non-smoking pregnant women with asthma were participants in a randomised controlled trial of exhaled nitric oxide guided treatment adjustment. Rhinitis was assessed using a visual analogue scale (VAS) scored from 0 to 10 and classified as current (VAS > 2.5), moderate/severe versus mild (VAS > 6 vs <5), atopic versus non-atopic and pregnancy rhinitis. At baseline, women completed the 20-Item Sino-Nasal Outcome Test (SNOT20), asthma specific (AQLQ-M) QoL questionnaires and the Six-Item Short-Form State Trait Anxiety Inventory (STAI-6). Asthma control was assessed using the asthma control questionnaire (ACQ). Perinatal outcomes were collected after delivery. RESULTS: Current rhinitis was present in 142 (65%) women including 45 (20%) women who developed pregnancy rhinitis. Women with current rhinitis had higher scores for ACQ (p = 0.004), SNOT20 (p < 0.0001) and AQLQ-M (p < 0.0001) compared to women with no rhinitis. Current rhinitis was associated with increased anxiety symptoms (p = 0.002), rhinitis severity was associated with higher ACQ score (p = 0.004) and atopic rhinitis was associated with poorer lung function (p = 0.037). Rhinitis symptom severity improved significantly during gestation (p < 0.0001). There was no impact on perinatal outcomes. Improved asthma control was associated with improvement in rhinitis. CONCLUSION: Rhinitis in pregnant women with asthma is common and associated with poorer asthma control, sino-nasal and asthma specific QoL impairment and anxiety. In the context of active asthma management there was significant improvement in rhinitis symptoms and severity as pregnancy progressed. PMID- 26365759 TI - Involvement of Dimethyl Sulfide and Several Polyfunctional Thiols in the Aromatic Expression of the Aging Bouquet of Red Bordeaux Wines. AB - The development of an aromatic bouquet during fine wine aging depends on complex transformations occurring in a reductive atmosphere, favorable to the formation and preservation of sulfur odorants, such as dimethyl sulfide (DMS) and polyfunctional thiols. The aim of this study was to address their role in the occurrence, evolution, and perceived sensory nuances of the aging bouquet of red Bordeaux wines. These compounds were quantified in 24 wines and scored by a professional wine panel for the degree to which they reflected the aging bouquet olfactory concept. Partial least square (PLS) analysis, combining sensory and quantitative chemical data, predicted that DMS, 2-furanmethanethiol, and 3 sulfanylhexanol concentrations correlated with the typicality score, discriminating highly-typical wines from less-typical ones. Several vintages from three vineyards were then subjected to sensory and chemical analysis to determine how aging bouquet typicality and the intensity of five key aromatic notes (undergrowth, truffle, fresh fruit, toasted, and empyreumatic) evolved during bottle storage in relation to these three sulfur odorants. PCA analysis emphasized their combined impact on aging bouquet typicality and their contribution to undergrowth, truffle, and empyreumatic attributes. PMID- 26365760 TI - Applying the RE-AIM Framework to Evaluate Integrative Medicine Group Visits Among Diverse Women with Chronic Pelvic Pain. AB - The purpose of this study was to evaluate group medical visits using an integrative health approach for underserved women with chronic pelvic pain (CPP). We implemented an integrative medicine program to improve quality of life among women with CPP using Centering, a group-based model that combines healthcare assessment, education, and social support. Patients were from university affiliated and public hospital-affiliated clinics. We evaluated the program with qualitative and quantitative data to address components of the RE-AIM framework: Reach, Effectiveness, Adoption, Implementation, and Maintenance. Participants of the Centering CPP Program participants (n = 26) were demographically similar to a sample of women with CPP who sought care at Bay Area hospitals (n = 701). Participants were on average 40 years of age, a majority of whom were racial/ethnic minorities with low household income (76%). Women who attended four or more sessions (n = 16) had improved health-related quality of life, including decreases in average number of unhealthy days in the past month (from 24 to 18, p < .05), depressive symptoms (from 11.7 to 9.0, p < .05), and symptom severity (from 4.2 to 3.1, p < .01). Sexual health outcomes also improved (30.5 to 50.3, p = .02). No improvements were observed for pain catastrophizing. Our pilot program provides preliminary data that an integrative health approach using a group-based model can be adapted and implemented to reach diverse women with CPP to improve physical and psychological well-being. Given these promising findings, rigorous evaluation of implementation and effectiveness of this approach compared with usual care is warranted. PMID- 26365761 TI - Hong-Ou-Mandel Interference with a Single Atom. AB - The Hong-Ou-Mandel (HOM) effect is widely regarded as the quintessential quantum interference phenomenon in optics. In this work we examine how nonlinearity can smear statistical photon bunching in the HOM interferometer. We model both the nonlinearity and a balanced beam splitter with a single two-level system and calculate a finite probability of anti-bunching arising in this geometry. We thus argue that the presence of such nonlinearity would reduce the visibility in the standard HOM setup, offering some explanation for the diminution of the HOM visibility observed in many experiments. We use the same model to show that the nonlinearity affects a resonant two-photon propagation through a two-level impurity in a waveguide due to a "weak photon blockade" caused by the impossibility of double-occupancy and argue that this effect might be stronger for multi-photon propagation. PMID- 26365763 TI - DNA damage and oxidative stress induced at low doses by the fungicide hexachlorobenzene in human intestinal Caco-2 cells. AB - CONTEXT: Hexachlorobenzene (HCB), a persistent chlorinated organic chemical, could be detected in human tissues in several countries of the world. Human exposure to Persistent Organic Pollutants (POPs) occurring primarily through diet, HCB and its metabolites are therefore supposed to interact directly with intestinal mucosa. OBJECTIVE: The aim of this study was to investigate the possible effects of low doses of HCB on DNA integrity, cellular viability, differentiation and oxidative status in vitro in human colonic carcinoma cell line Caco-2. MATERIALS AND METHODS: Cells were exposed to increasing doses of HCB for 14 days to assess the cytotoxic, genotoxic and oxidative properties of this compound. The involvement of oxidative stress in the observed effects was evaluated by co exposure of Caco-2 cells with HCB and alpha-tocopherol. RESULTS: Exposure of Caco-2 cells to HCB resulted in a dose-dependent cytotoxicity, DNA damages and alterations of the cell layer integrity and the barrier function. Moreover, exposure of Caco-2 cells to HCB led to an enhancement of H(2)O(2) production and to an increased activity of antioxidant enzymes. In addition, Co exposure of Caco-2 cells to HCB and alpha-tocopherol reversed the effects observed in cells exposed to HCB alone. CONCLUSION: These results suggested that HCB effects on Caco-2 cells could be linked, at least in part, to its pro oxidative potential. PMID- 26365762 TI - The role of genetically engineered pigs in xenotransplantation research. AB - There is a critical shortage in the number of deceased human organs that become available for the purposes of clinical transplantation. This problem might be resolved by the transplantation of organs from pigs genetically engineered to protect them from the human immune response. The pathobiological barriers to successful pig organ transplantation in primates include activation of the innate and adaptive immune systems, coagulation dysregulation and inflammation. Genetic engineering of the pig as an organ source has increased the survival of the transplanted pig heart, kidney, islet and corneal graft in non-human primates (NHPs) from minutes to months or occasionally years. Genetic engineering may also contribute to any physiological barriers that might be identified, as well as to reducing the risks of transfer of a potentially infectious micro-organism with the organ. There are now an estimated 40 or more genetic alterations that have been carried out in pigs, with some pigs expressing five or six manipulations. With the new technology now available, it will become increasingly common for a pig to express even more genetic manipulations, and these could be tested in the pig-to-NHP models to assess their efficacy and benefit. It is therefore likely that clinical trials of pig kidney, heart and islet transplantation will become feasible in the near future. PMID- 26365764 TI - A porous proton-relaying metal-organic framework material that accelerates electrochemical hydrogen evolution. AB - The availability of efficient hydrogen evolution reaction (HER) catalysts is of high importance for solar fuel technologies aimed at reducing future carbon emissions. Even though Pt electrodes are excellent HER electrocatalysts, commercialization of large-scale hydrogen production technology requires finding an equally efficient, low-cost, earth-abundant alternative. Here, high porosity, metal-organic framework (MOF) films have been used as scaffolds for the deposition of a Ni-S electrocatalyst. Compared with an MOF-free Ni-S, the resulting hybrid materials exhibit significantly enhanced performance for HER from aqueous acid, decreasing the kinetic overpotential by more than 200 mV at a benchmark current density of 10 mA cm(-2). Although the initial aim was to improve electrocatalytic activity by greatly boosting the active area of the Ni-S catalyst, the performance enhancements instead were found to arise primarily from the ability of the proton-conductive MOF to favourably modify the immediate chemical environment of the sulfide-based catalyst. PMID- 26365765 TI - Habenula Lesions Reveal that Multiple Mechanisms Underlie Dopamine Prediction Errors. AB - Dopamine (DA) neurons are thought to facilitate learning by signaling reward prediction errors (RPEs), the discrepancy between actual and expected reward. However, how RPEs are calculated remains unknown. It has been hypothesized that DA neurons receive RPE signals from the lateral habenula. Here, we tested how lesions of the habenular complex affect the response of optogenetically identified DA neurons in mice. We found that lesions impaired specific aspects of RPE signaling in DA neurons. The inhibitory responses caused by reward omission were greatly diminished while inhibitory responses to aversive stimuli, such as air puff-predictive cues or air puff, remained unimpaired. Furthermore, we found that after habenula lesions, DA neurons' ability to signal graded levels of positive RPEs became unreliable, yet significant excitatory responses still remained. These results demonstrate that the habenula plays a critical role in DA RPE signaling but suggest that it is not the exclusive source of RPE signals. PMID- 26365766 TI - The Formation of Hierarchical Decisions in the Visual Cortex. AB - Intelligence relies on our ability to find appropriate sequences of decisions in complex problem spaces. The efficiency of a problem solver depends on the speed of its individual decisions and the number of decisions it can explore in parallel. It remains unknown whether the primate brain can consider multiple decisions at the same time. We therefore trained monkeys to navigate through a decision tree with stochastic sensory evidence at multiple branching points and recorded neuronal activity in visual cortical areas V1 and V4. We found a first phase of decision making in which neuronal activity increased in parallel along multiple branches of the decision tree. This was followed by an integration phase where the optimal overall strategy crystallized as the result of interactions between local decisions. The results reveal how sensory evidence is integrated efficiently for hierarchical decisions and contribute to our understanding of the brain mechanisms that implement complex mental programs. PMID- 26365768 TI - Trends in sources and sharing of needles among people who inject drugs, San Francisco, 2005-2012. AB - BACKGROUND: Globally, people who inject drugs (PWID) are disproportionately at risk for HIV and HCV due to risky injection drug use behaviors, such as sharing used needles and injection kits. In response, San Francisco, one of several cities with a sizable PWID population that had quickly committed to stopping the spread of HIV/HCV, have expanded needle access, including in pharmacies and hospitals, in order to ensure that PWID inject with clean needles. However, there was no current research on whether each source of needles is equally associated with always using new sterile needles in San Francisco. Furthermore, no research in San Francisco had examined behavioral trends in needle-sharing practices, the relationship between PWID and their injection partners, and knowledge of their injection partners' HIV or HCV status. METHODS: Therefore, we analyzed data from three cycles of the National HIV Behavioral Surveillance studies from 2005 to 2012 in San Francisco among PWID. RESULTS: The results from our analysis suggest that overall risky drug injection practices, such as injecting with used needles, sharing used cookers or water, and dividing drugs with a used syringe, among PWID in San Francisco has decreased from 2005 to 2012. An increasing proportion of PWID are injecting with their friend/acquaintance than with their sex partner. Also, a declining portion of PWID report knowing their last injection partner's HIV-positive or HCV-positive status. In terms of sources of needles, less PWID are getting their needles from friends and drug dealers while a greater proportion are using pharmacies and needle exchanges. However, pharmacies as a source of needles are negatively associated with always using new sterile needles. CONCLUSION: From 2005 to 2012, overall high-risk injection behavior among PWID in SF has decreased including PWID that are injecting with others. However, our results suggest caution over the expansion of pharmacies as a source of needles in San Francisco and in similar cities due to their negative association with always using a new sterile needle. Since more PWID are injecting with their friend/acquaintance, interventions at needle access programs at pharmacies, hospitals, and needle exchanges should stress the potential to transmit HIV and HCV even in one-on-one sharing situations. Furthermore, since a decreasing percentage of PWID know about their injection partner's HIV/HCV status, such interventions should also highlight the importance of having a conversation about HIV and HCV status with one's injecting partner. PMID- 26365767 TI - Connecting Neural Codes with Behavior in the Auditory System of Drosophila. AB - Brains are optimized for processing ethologically relevant sensory signals. However, few studies have characterized the neural coding mechanisms that underlie the transformation from natural sensory information to behavior. Here, we focus on acoustic communication in Drosophila melanogaster and use computational modeling to link natural courtship song, neuronal codes, and female behavioral responses to song. We show that melanogaster females are sensitive to long timescale song structure (on the order of tens of seconds). From intracellular recordings, we generate models that recapitulate neural responses to acoustic stimuli. We link these neural codes with female behavior by generating model neural responses to natural courtship song. Using a simple decoder, we predict female behavioral responses to the same song stimuli with high accuracy. Our modeling approach reveals how long timescale song features are represented by the Drosophila brain and how neural representations can be decoded to generate behavioral selectivity for acoustic communication signals. PMID- 26365769 TI - The imperative to integrate suicide prevention within community-based harm reduction programs for people who inject drugs: Informed by the situation in Delhi, India. PMID- 26365770 TI - Rates and precipitating factors for postpartum depression following screening in consecutive births. AB - OBJECTIVE: To measure the recurrence rate and precipitating factors of postpartum depression (PPD) following universal screening using the Edinburgh Postnatal Depression Scale (EPDS) in consecutive births. METHODS: EPDS questionnaires were administered to all postpartum women at our hospital beginning in June 2008. For this study, perinatal factors were examined in relation to EPDS scores during consecutive births to identify factors in the development of PPD. Outcomes of women previously screening negative and returning for another delivery were analyzed using univariable and multivariable analysis for associations with PPD. RESULTS: Between June 2008 and March 2010, 17 613 women were screened using EPDS questionnaires, and 3842 (22%) women returned and subsequently delivered another infant. A prior negative EPDS score significantly reduced the risk of a subsequent positive EPDS when compared with index testing (3% versus 6%; p < 0.01). Of those 3631 women previously screening negative and returning for a subsequent delivery, stillbirth and neonatal malformation were both associated with increased risk of PPD, p = 0.01 and p = 0.02, respectively. Following logistic regression, stillbirth remained significantly associated with symptoms of PPD (aOR 7.79, 95%CI 1.5-39.5). CONCLUSIONS: While prior negative screening portends a reduced risk for PPD, stillbirth in a subsequent pregnancy remains a powerful antecedent for PPD. PMID- 26365771 TI - Host-directed therapies for improving poor treatment outcomes associated with the middle east respiratory syndrome coronavirus infections. AB - Three years after its first discovery in Jeddah Saudi Arabia, the novel zoonotic pathogen of humans, the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) continues to be a major threat to global health security.(1) Sporadic community acquired cases of MERS continue to be reported from the Middle East. The recent nosocomial outbreaks in hospitals in Seoul, Korea and at the National Guard Hospital in Riyadh, Saudi Arabia indicate the epidemic potential of MERS-CoV. Currently there are no effective anti-MERS-CoV anti-viral agents or therapeutics and MERS is associated with a high mortality rate (40%) in hospitalised patients. A large proportion of MERS patients who die have a range of pulmonary pathology ranging from pneumonia to adult respiratory distress syndrome with multi-organ failure, compounded by co-morbidities, reflecting a precarious balance of interactions between the host-immune system and MERS-CoV. Whilst we wait for new MERS-CoV specific drugs, therapeutics and vaccines to be developed, there is a need to advance a range of Host-Directed Therapies. A range of HDTs are available, including commonly used drugs with good safety profiles, which could augment host innate and adaptive immune mechanisms to MERS-CoV, modulate excessive inflammation and reduce lung tissue destruction. We discuss the rationale and potential of using Host-Directed Therapies for improving the poor treatment outcomes associated with MERS. Carefully designed randomized controlled trials will be needed to determine whether HDTs could benefit patients with MERS. The recurrent outbreaks of MERS-CoV infections at hospitals in the Middle East present unique opportunities to conduct randomized clinical trials. The time has come for a more coordinated global response to MERS and a multidisciplinary global MERS-CoV response group is required to take forward priority research agendas. PMID- 26365772 TI - c-ETS transcription factors play an essential role in the licensing of human MCM4 origin of replication. AB - In metazoans, DNA replication is a highly regulated and ordered process that occurs during the S phase of cell cycle. It begins with the licensing of origins of replication usually found in close proximity of actively transcribing genes owing perhaps to a profound influence of transcription factors on the epigenetic signatures and architecture of chromatin. Here we show that ETS transcription factors are novel regulators of MCM4 origin, whose binding sites are localized between two divergently transcribing MCM4 and PRKDC genes. c-ETS1 and c-ETS2 were recruited to the MCM4 origin respectively during the S and G1 phases of cell cycle. c-ETS2 binding was facilitated by an active chromatin distinguished by acetylated histone H3 orchestrated by histone acetyl transferase GCN5 and followed by HBO1 mediated histone H4 acetylation. Interestingly, c-ETS2 overexpression led to increased BrdU incorporation in the S phase cells while its down-regulation by RNA interference compromised the loading of pre-replicative complex at the origin. Conversely, the recruitment of c-ETS1 at the origin coincided with histone H3 methylation signature characteristic of closed chromatin conformation. As expected, enforced expression of c-ETS1 severely compromised DNA replication whereas its down-regulation enhanced DNA replication as evident from increased BrdU incorporation. Thus, c-ETS transcription factors appear to be key regulators of MCM4 origin where c-ETS2 seems to promote DNA replication whereas c-ETS1 functions as a negative regulator. PMID- 26365773 TI - Communication attitudes in children who stutter: A meta-analytic review. AB - BACKGROUND: This article presents a meta-analytic review of differences in communication attitudes between children who stutter (CWS) and children who do not stutter (CWNS). METHOD: To be included in this review, the studies had to include a group of CWS and CWNS between the ages of 3-18 years and a measurement of communication attitudes. The journal articles were identified by using the key words stutter*, speech disfluenc*, fluency disorder*, and stammer* cross referenced to awareness*, reaction*, attitude*, KiddyCAT, CAT, A-19 Scale, PASS and OASES. RESULTS: A total of 18 studies met the inclusion criteria for this meta-analysis. The results showed that CWS exhibit more negative communication attitudes than CWNS from the preschool years. The differences between the groups increased with age, but were not influenced by gender. CONCLUSION: The results indicate that negative communication attitudes can be an effect of stuttering. Key issues requiring further investigation are whether communication attitudes differ as a function of age at stuttering onset and whether communication attitudes influence the development of stuttering. EDUCATIONAL OBJECTIVES: After reading this article, the reader will be able to: (a) summarise empirical findings with regard to the relationship between communication attitudes and childhood stuttering; (b) describe the different instruments used to measure communication attitudes; (c) discuss the relationship between communication attitudes, age and gender. PMID- 26365774 TI - Mutations in GNAL gene in 214 cases with isolated dystonia. PMID- 26365775 TI - Mutations in RNF216 do not cause 4H syndrome. AB - We comment on the recent publication by Ganos et al. [1] classifying a patient with non-specific white matter abnormalities, cerebellar atrophy, hypogonadotropic hypogonadism and absent lower median incisors as 4H syndrome. He had mutations in RNF216. Mutations in this gene cause Gordon-Holmes syndrome, distinct from 4H syndrome. PMID- 26365776 TI - Selective attentional deficit in essential tremor: Evidence from the attention network test. AB - INTRODUCTION: The traditional view of essential tremor (ET) as a monosymptomatic and benign disorder has been reconsidered after patients with ET have been shown to experience cognitive deficits that are also related to attention. The Attention Network Test (ANT) is a rapid, widely used test to measure the efficiency of three attentional networks, i.e. alerting, orienting and executive, by evaluating reaction times (RTs) in response to visual stimuli. The aim of this study was to investigate attentional functioning in ET patients by means of the ANT. METHODS: 21 non-demented patients with ET and 21 age- and sex-matched healthy controls performed the ANT. RESULTS: RT was significantly longer in ET patients than in controls (p < 0.001). Moreover, a significant difference in alerting and executive efficiency (p = 0.003 and p = 0.01 respectively) was found between groups, while the difference in the orienting efficiency only bordered on significance. CONCLUSION: Our results point to a difficulty in the alerting and executive domains of attention in ET patients, probably owing to a dysfunction in the cerebello-thalamo-cortical loop. These selective attentional deficits are not related to clinical motor symptoms, contributing to shed further light on the clinical picture of ET. PMID- 26365777 TI - Multiple system atrophy-mimicking conditions: Diagnostic challenges. AB - Multiple system atrophy (MSA) is a relentless progressive disorder without effective treatment. Its accurate diagnosis is important for the management of individual patients and for the development of new therapeutic strategies. However, there are many disorders which can mimic MSA (so-called 'MSA look alikes'), and the true rate for over- or under-diagnoses of MSA is not known, especially during the early course of disease when the disease is not fully developed yet. Herein, the authors review the neurodegenerative, genetic, and immunologic conditions that can mimic MSA and thus be part of the differential diagnosis of MSA. Clinicians should be aware of these conditions and be able to differentiate them by clinical features and laboratory findings. PMID- 26365778 TI - Functional (psychogenic) movement disorders - Clinical presentations. AB - Functional or psychogenic movement disorders are common and disabling, and sometime difficult to diagnose. The history and physical exam can give positive features that will support the diagnosis, which should not be based solely on exclusion. Some clues in the history are sudden onset, intermittent time course, variability of manifestation over time, childhood trauma, history of other somatic symptom and secondary gain. Anxiety and depression are common, but not necessarily more than the general population. On examination, distraction and suggestibility may be present. There are specific signs that should be looked for with different types of movements. For example, with tremor, change in frequency over time and entrainment are common features. With myoclonus, the movements might be complex in type with long latencies to stimulus induced jerks. Gait disorders show good balance despite claims to the contrary. Functional dystonia still remains a challenging diagnosis in many circumstances, although fixed dystonia is one sign more likely to be functional. PMID- 26365779 TI - What is the evidence to support home environmental adaptation in Parkinson's disease? A call for multidisciplinary interventions. AB - "Home" is where one has a sense of belonging and feels secure, but it can also be a risky place for people with Parkinson's disease (PD). PD patients need assistance making adjustments to their physical environment to maintain appropriate care and provide a safe environment. This relationship is called the "person-environmental fit" (P-E fit). While most PD patients remain in their own homes, little is known about the specific challenges that PD patients and their caregivers encounter in the routine activities of daily living. The aim of our study was to identify the existing evidence on the issue of housing environmental adaptation in PD by performing a systematic review with a proposal of development strategies to integrate a multidisciplinary team into a home environmental research. MEDLINE, and life science journals were searched by querying appropriate key words, but revealed very few publications in this area. However, early evidence suggested that PD patients do not enjoy an adequate P-E fit in their own homes and face more functional limitations compared to matched controls. We concluded that we need to develop research-based evaluation strategies that can provide us with a theoretical and conceptual basis as well as tools for analysis of the P-E fit for PD patients and caregivers. We recommend that individual members of the multidisciplinary team including patients, caregivers, physicians, rehabilitation specialists, and social workers use a team approach to identify the key indicators and solutions for the development of PD specific solutions for improving the P-E fit. PMID- 26365780 TI - Pheochromocytoma - when acute medicine comes to the surgeon's rescue and vice versa. Case report of a patient presenting unmanageable haemodynamic instability during elective surgery for pheochromocytoma. AB - We report and discuss the case of a 51-year-old patient undergoing elective laparoscopic surgery for pheochromocytoma after 10 days of medical pre-treatment. After anaesthetic induction, a deep level of anaesthesia could not prevent the onset of repeated hypertensive peaks, followed by severe hypotensive periods. Once the surgical incision was made, the patient developed acute pulmonary oedema along with significant oxygen desaturation. The decision was made to stop the surgery and transfer the patient to the intensive care unit (ICU) for further support and management. Unfortunately, additional monitoring and symptomatic treatment did not help haemodynamic stabilisation. In the absence of any external stimulation or medical support, the oscillation of blood pressure (BP) continued with peaks every 20 minutes up to 300 mmHg systolic blood pressure (SBP) and falls down to 30 mmHg SBP. The patient also sustained two episodes of cardiac arrest from which he recovered. Facing this unmanageable situation, a decision was made after a multi-disciplinary discussion to go back to surgery in order to remove the source of adrenergic stimulation. Surgery by laparotomy was performed and catecholamine substitution was provided. Nevertheless, after tumour removal, BP dropped leading to a third cardiac arrest that was successfully managed. Following a 10-day stay in the ICU, the patient left with subsequent cardiac stabilisation and full recovery. PMID- 26365781 TI - Enzymatically-responsive pro-angiogenic peptide-releasing poly(ethylene glycol) hydrogels promote vascularization in vivo. AB - Therapeutic angiogenesis holds great potential for a myriad of tissue engineering and regenerative medicine approaches. While a number of peptides have been identified with pro-angiogenic behaviors, therapeutic efficacy is limited by poor tissue localization and persistence. Therefore, poly(ethylene glycol) hydrogels providing sustained, enzymatically-responsive peptide release were exploited for peptide delivery. Two pro-angiogenic peptide drugs, SPARC113 and SPARC118, from the Secreted Protein Acidic and Rich in Cysteine, were incorporated into hydrogels as crosslinking peptides flanked by matrix metalloproteinase (MMP) degradable substrates. In vitro testing confirmed peptide drug bioactivity requires sustained delivery. Furthermore, peptides retain bioactivity with residual MMP substrates present after hydrogel release. Incorporation into hydrogels achieved enzymatically-responsive bulk degradation, with peptide release in close agreement with hydrogel mass loss and released peptides retaining bioactivity. Interestingly, SPARC113 and SPARC118-releasing hydrogels had significantly different degradation time constants in vitro (1.16 and 8.77*10(-2) h(-1), respectively), despite identical MMP degradable substrates. However, upon subcutaneous implantation, both SPARC113 and SPARC118 hydrogels exhibited similar degradation constants of ~1.45*10(-2) h(-1), and resulted in significant ~1.65-fold increases in angiogenesis in vivo compared to controls. Thus, these hydrogels represent a promising pro-angiogenic approach for applications such as tissue engineering and ischemic tissue disorders. PMID- 26365783 TI - The Environmental Impact on Occupational Therapy Interventions. AB - The purpose of this study was to investigate how the environment influenced the intervention choices occupational therapists made for patients recovering from a stroke in an inpatient rehabilitation hospital. Three occupational therapists were observed providing intervention for six patients over a 16-month period. Treatment spaces included a therapy gym, gym with kitchen combination, and a home like space. Furniture was added to the therapy gym to be more home-like midway through the study. Observations included therapist selection of treatment location and interventions, and observational data of the environment and interactions among therapists and patients. This study found that inpatient rehabilitation environments did influence interventions. The occupational therapists provided therapy in the standard therapy gym environment most often, whether it was enhanced to be more home-like or not, and predominately used preparatory methods. PMID- 26365782 TI - Resolution of structure of PIP5K1A reveals molecular mechanism for its regulation by dimerization and dishevelled. AB - Type I phosphatidylinositol phosphate kinase (PIP5K1) phosphorylates the head group of phosphatidylinositol 4-phosphate (PtdIns4P) to generate PtdIns4,5P2, which plays important roles in a wide range of cellular functions including Wnt signalling. However, the lack of its structural information has hindered the understanding of its regulation. Here we report the crystal structure of the catalytic domain of zebrafish PIP5K1A at 3.3 A resolution. This molecule forms a side-to-side dimer. Mutagenesis study of PIP5K1A reveals two adjacent interfaces for the dimerization and interaction with the DIX domain of the Wnt signalling molecule dishevelled. Although these interfaces are located distally to the catalytic/substrate-binding site, binding to these interfaces either through dimerization or the interaction with DIX stimulates PIP5K1 catalytic activity. DIX binding additionally enhances PIP5K1 substrate binding. Thus, this study elucidates regulatory mechanisms for this lipid kinase and provides a paradigm for the understanding of PIP5K1 regulation by their interacting molecules. PMID- 26365784 TI - Do statins prevent acute kidney injury? AB - INTRODUCTION: Statins were introduced as lipid-lowering agents with a specific action to decrease plasma cholesterol concentrations and they have led to significant reductions in cardiovascular morbidity and mortality. Since their introduction, they have been found to have highly pleiotropic effects and potential use in many medical conditions well beyond cardiovascular disease alone. With their widespread and increasing use, adverse effects have also become apparent and it is suggested from the interrogation of observational data from large datasets that an early complication of statin use may be acute kidney injury (AKI). AREAS COVERED: This review explores the evidence relating to statins and the risks of AKI. The pathophysiology of AKI is considered and the statins are compared and contrasted. Statins have also been attributed with reno protective effects and the literature relating to these circumstances are reviewed. EXPERT OPINION: The question of whether statins cause AKI remains unresolved. Evidence suggests that statins may both protect or harm kidneys acutely and that risk varies with the condition and the dose and type of statin used. However, any current adverse data should not deter prescription of statins in patients where there is clear evidence for either primary or secondary prevention of cardiovascular events. PMID- 26365785 TI - Revisiting the 'Gadgil effect': do interguild fungal interactions control carbon cycling in forest soils? AB - In forest ecosystems, ectomycorrhizal and saprotrophic fungi play a central role in the breakdown of soil organic matter (SOM). Competition between these two fungal guilds has long been hypothesized to lead to suppression of decomposition rates, a phenomenon known as the 'Gadgil effect'. In this review, we examine the documentation, generality, and potential mechanisms involved in the 'Gadgil effect'. We find that the influence of ectomycorrhizal fungi on litter and SOM decomposition is much more variable than previously recognized. To explain the inconsistency in size and direction of the 'Gadgil effect', we argue that a better understanding of underlying mechanisms is required. We discuss the strengths and weaknesses of each of the primary mechanisms proposed to date and how using different experimental methods (trenching, girdling, microcosms), as well as considering different temporal and spatial scales, could influence the conclusions drawn about this phenomenon. Finally, we suggest that combining new research tools such as high-throughput sequencing with experiments utilizing natural environmental gradients will significantly deepen our understanding of the 'Gadgil effect' and its consequences on forest soil carbon and nutrient cycling. PMID- 26365786 TI - Involvement of lateral septum in alcohol's dopamine-elevating effect in the rat. AB - Drugs of abuse share the ability to increase extracellular dopamine (DA) levels in the mesolimbic DA system. This effect has been linked to positive and reinforcing experiences of drug consumption and is presumed to be of importance for continued use, as well as for the development of dependence and addiction. Previous rat studies from our lab have implicated a neuronal circuitry involving glycine receptors in nucleus accumbens (nAc) and, secondarily, nicotinic acetylcholine receptors in the ventral tegmental area (VTA) in ethanol's (EtOH) DA-elevating effect. The work presented here, performed in male Wistar rats, suggests that the lateral septum (LS), which has previously been associated with different aspects of EtOH-related behaviour, is involved as well. In vivo microdialysis methodology demonstrated that blocking the generation of action potentials in LS using tetrodotoxin prevented a DA increase in nAc after accumbal EtOH perfusion. Retrograde tracing and polymerase chain reaction (PCR) were used to identify and characterize cells projecting to VTA from nAc/LS and from LS to nAc. Based on the PCR results, cells projecting from both LS/nAc to anterior VTA and from LS to nAc were mainly GABAergic neurons expressing glycine receptors, and these cells are presumed to be involved in mediating the DA-elevating effect of EtOH. These results provide further evidence implicating LS in the reinforcing effects of EtOH. Additional studies are needed to investigate LS involvement in EtOH consumption behaviour and its potential role in the development of dependence and addiction. PMID- 26365787 TI - Metabolic changes at the early stage of sepsis induced by cecal ligation and puncture in rats and the interventional effects of Huang-Lian-Jie-Du-Tang. AB - Sepsis is a disease with high mortality that requires rapid diagnosis and treatment. This study used a metabolomic approach to profile the metabolic changes at the early stage of sepsis induced by cecal ligation and puncture (CLP) in rats and investigated the interventional effects of Huang-Lian-Jie-Du-Tang (HLJDT). Male SD rats were intragastrically administered 270mg/kg HLJDT 2h prior to CLP, serum extracts were profiled by liquid chromatography/quadrupole time-of flight mass spectrometer (LC-Q-TOF-MS) and multivariate analytical (MVA) methods were employed to evaluate the metabolic changes of extracts. A Partial Least Squares Discriminant Analysis (PLS-DA) score plot indicated that septic rats undergo significant metabolic changes 2h after CLP, and HLJDT administration could reverse the metabolic changes induced by CLP. Sixteen biomarkers involved in amino acid metabolism, unsaturated fatty acid metabolism, purine metabolism, and lipid metabolism were identified after Orthogonal Partial Least-Squares Analysis (OPLS). Among the 16 metabolites, 10 were regulated by HLJDT. This study established the foundation for further research of the early diagnosis biomarkers and therapeutic evaluation biomarkers discovery of sepsis. PMID- 26365788 TI - Short-term test-retest reliability of resting state fMRI metrics in children with and without attention-deficit/hyperactivity disorder. AB - To date, only one study has examined test-retest reliability of resting state fMRI (R-fMRI) in children, none in clinical developing groups. Here, we assessed short-term test-retest reliability in a sample of 46 children (11-17.9 years) with attention-deficit/hyperactivity disorder (ADHD) and 57 typically developing children (TDC). Our primary test-retest reliability measure was the intraclass correlation coefficient (ICC), quantified for a range of R-fMRI metrics. We aimed to (1) survey reliability within and across diagnostic groups, and (2) compare voxel-wise ICC between groups. We found moderate-to-high ICC across all children and within groups, with higher-order functional networks showing greater ICC. Nearly all R-fMRI metrics exhibited significantly higher ICC in TDC than in children with ADHD for one or more regions. In particular, posterior cingulate and ventral precuneus exhibited group differences in ICC across multiple measures. In the context of overall moderate-to-high test-retest reliability in children, regional differences in ICC related to diagnostic groups likely reflect the underlying pathophysiology for ADHD. Our currently limited understanding of the factors contributing to inter- and intra-subject variability in ADHD underscores the need for large initiatives aimed at examining their impact on test-retest reliability in both clinical and developing populations. PMID- 26365789 TI - General Characterization Methods for Photoelectrochemical Cells for Solar Water Splitting. AB - Photoelectrochemical (PEC) water splitting is a very promising technology that converts water into clean hydrogen fuel and oxygen by using solar light. However, the characterization methods for PEC cells are diverse and a systematic introduction to characterization methods for PEC cells has rarely been attempted. Unlike most other review articles that focus mainly on the material used for the working electrodes of PEC cells, this review introduces general characterization methods for PEC cells, including their basic configurations and methods for characterizing their performance under various conditions, regardless of the materials used. Detailed experimental operation procedures with theoretical information are provided for each characterization method. The PEC research area is rapidly expanding and more researchers are beginning to devote themselves to related work. Therefore, the content of this Minireview can provide entry-level knowledge to beginners in the area of PEC, which might accelerate progress in this area. PMID- 26365790 TI - Effects of different sources of physically effective fiber on rumen microbial populations. AB - Physically effective fiber is needed by dairy cattle to prevent ruminal acidosis. This study aimed to examine the effects of different sources of physically effective fiber on the populations of fibrolytic bacteria and methanogens. Five ruminally cannulated Holstein cows were each fed five diets differing in physically effective fiber sources over 15 weeks (21 days/period) in a Latin Square design: (1) 44.1% corn silage, (2) 34.0% corn silage plus 11.5% alfalfa hay, (3) 34.0% corn silage plus 5.1% wheat straw, (4) 36.1% corn silage plus 10.1% wheat straw, and (5) 34.0% corn silage plus 5.5% corn stover. The impact of the physically effective fiber sources on total bacteria and archaea were examined using denaturing gradient gel electrophoresis. Specific real-time PCR assays were used to quantify total bacteria, total archaea, the genus Butyrivibrio, Fibrobacter succinogenes, Ruminococcus albus, Ruminococcus flavefaciens and three uncultured rumen bacteria that were identified from adhering ruminal fractions in a previous study. No significant differences were observed among the different sources of physical effective fiber with respect to the microbial populations quantified. Any of the physically effective fiber sources may be fed to dairy cattle without negative impact on the ruminal microbial community. PMID- 26365791 TI - IUDs at 1 year: predictors of early discontinuation. AB - OBJECTIVE: To assess baseline dysmenorrhea and insertion-related pain as predictors of intrauterine device (IUD) removal within 1 year following insertion. STUDY DESIGN: System-wide medical record abstraction 1 year after IUD insertion to identify removals and comparison of baseline characteristics (dysmenorrhea, insertion pain) among women with a removal versus women who continued IUD use was used. Baseline data came from a randomized trial of pain control during insertion. RESULTS: Among 199 insertions, we identified 21 removals and 7 expulsions, a continuation rate of 85.9%. Women with IUD removal had higher median dysmenorrhea scores before insertion than those who continued (42 vs. 25.5, p=.03). Insertion pain and other characteristics were not associated with removal. CONCLUSIONS: Preexisting dysmenorrhea may predict IUD removal within 1 year. PMID- 26365792 TI - Prediction of nomegestrol acetate pharmacokinetics in healthy female adolescents and adults by whole-body physiology-based pharmacokinetic modelling and clinical validation. AB - OBJECTIVE: Nomegestrol acetate (NOMAC), a selective progestogen, and 17beta estradiol (E2), which is identical to endogenous oestrogen, are components of a new monophasic combined oral contraceptive--NOMAC/E2. This study aimed to compare pharmacokinetics (PK) of NOMAC in adolescent and adult women following a single dose of NOMAC/E2. STUDY DESIGN: Healthy postmenarcheal adolescent (14-17years) and adult (18-50years) women received a single dose of NOMAC/E2 (2.5mg/1.5mg) in this single-centre, open-label, parallel-group Phase 1 study (EudraCT# 2008 002142-38). Blood samples were obtained for PK analysis, and concentrations of NOMAC, E2 and its metabolite estrone (E1) were determined for up to 129h following dosing to obtain PK data. An independent whole-body physiology-based pharmacokinetic (WB-PBPK) simulation model of NOMAC based on an independent Phase 3 dataset was used to scale NOMAC concentration-time plots to adolescents. RESULTS: Overall, 52 women were screened, of whom 30 (15 adolescents and 15 adults) were enrolled. No statistically significant differences were observed between the adolescent and adult groups for the clinically evaluated NOMAC PK parameters [maximum concentration (Cmax), area under the curve (AUC) and half life (t1/2)]. The PK of E2 and E1 showed extensive overlap between both age groups. The WB-PBPK model accurately predicted NOMAC AUC and Cmax values in both groups. CONCLUSIONS: No differences were observed in the clinically evaluated PK parameters for NOMAC between adolescent and adult women after a single dose of NOMAC/E2. The WB-PBPK model accurately predicted NOMAC PK data (EudraCT# 2008 002142-38). IMPLICATIONS: PK studies in adolescents are challenging because of ethical considerations. The whole-body physiology-based model described here complements classic noncompartmental and population PK approaches. The utility of this method is its ability to expand to adolescent postmenarcheal girls by using virtual postmenarcheal adolescent population data and applying physiological scaling. PMID- 26365793 TI - Overcoming language barriers: Matrix sentence tests with closed speech corpora. PMID- 26365794 TI - Effects of melatonin on diclofenac sodium treated rat kidney: a stereological and histopathological study. AB - OBJECTIVE: In this study, we aimed to investigate the effect of diclofenac sodium (DS) and melatonin (MEL) on kidney of the prenatally administered rats. MATERIALS AND METHODS: Pregnant rats were divided into the control, physiological saline, DS, and DS + MEL groups. All injections were given beginning from the 5th day after mating to the 15th day of the pregnancy. Physical dissector and Cavalieri principle were used to estimate the numerical density and total number of glomeruli and the volumetric parameters of kidney, respectively. RESULTS: Our stereological results indicated that DS application during the pregnancy lead to decrease in the mean volume, numerical density, and total number of the glomeruli (p < 0.05). In addition, we determined that usage of the MEL with the DS caused increases in the mean volume, numerical density, and total number of the glomeruli (p < 0.05). So, there was no significant difference in terms of the any parameter between the CONT and DS + MEL groups (p > 0.05). Light microscopic investigation showed congestion in blood vessels and shrinkage of the Bowman's space in the DS group. Moreover, there was degeneration in nephrons including glomerulosclerosis and tubular defects, and an increase in the connective tissue in the kidneys of the DS-treated group. However, usage of the MEL with the DS caused preventing of these pathological alterations in the kidney. DISCUSSION: We suggested that DS might lead to adverse effects in the kidneys of the rats that are prenatally subjected to this drug. Fortunately, these adverse effects can be prevented by the melatonin supplementation. PMID- 26365795 TI - Characterization of a novel full-length bovine endogenous retrovirus, BERV-beta1. AB - Recent studies have suggested that certain classes of endogenous retroviruses (ERVs) may be present in cattle. The aim of this study was increase the scope of knowledge regarding bovine ERVs. The ovine ERV beta1 pro/pol sequence was used to design a primer set for polymerase chain reaction (PCR) amplification of a similar sequence in the bovine genome. Through phylogenetic and bioinformatic analysis of the PCR product sequence together with its flanking region, a sequence 8107 bp in length was characterized. This sequence had a typical 5'-LTR gag-pro-pol-env-LTR-3' organization, and phylogenetic investigation defined it as a bovine ERV beta1. Thus, we were able to identify a novel bovine endogenous retrovirus element. PMID- 26365796 TI - Controlled topologies and self-assembly behaviors of oligomeric supra amphiphiles. AB - Trimeric and tetrameric supra-amphiphiles with rich self-assembly behaviors were fabricated in the adipic acid-dodecylamine mixed solution under the effect of hydrogen bonding. The hydrogen bonding can be switched "on" and "off"via pH variation and CO2 stimulus, thus leading to finely controlled topologies and self assembly behaviors of oligomeric supra-amphiphiles. PMID- 26365797 TI - A Subset of Human Bromodomains Recognizes Butyryllysine and Crotonyllysine Histone Peptide Modifications. AB - Bromodomains are epigenetic readers that are recruited to acetyllysine residues in histone tails. Recent studies have identified non-acetyl acyllysine modifications, raising the possibility that these might be read by bromodomains. Profiling the nearly complete human bromodomain family revealed that while most human bromodomains bind only the shorter acetyl and propionyl marks, the bromodomains of BRD9, CECR2, and the second bromodomain of TAF1 also recognize the longer butyryl mark. In addition, the TAF1 second bromodomain is capable of binding crotonyl marks. None of the human bromodomains tested binds succinyl marks. We characterized structurally and biochemically the binding to different acyl groups, identifying bromodomain residues and structural attributes that contribute to specificity. These studies demonstrate a surprising degree of plasticity in some human bromodomains but no single factor controlling specificity across the family. The identification of candidate butyryl- and crotonyllysine readers supports the idea that these marks could have specific physiological functions. PMID- 26365798 TI - The Design and Structure of Outer Membrane Receptors from Peroxisomes, Mitochondria, and Chloroplasts. AB - The eukaryotic cell is defined by compartments that allow specialization of function. This compartmental structure generates a new concept in cell biology compared with the simpler prokaryotic cell structure, namely the specific targeting of proteins to intracellular compartments. Protein targeting is achieved by the action of specialized signals on proteins destined for organelles that are recognized by cognate receptors. An understanding of the specificity of targeting signal recognition leading to import requires an understanding of the receptor structures. Here, we focus on the structures of receptors of different import machineries located on the outer membrane of three organelles: peroxisomes, mitochondria, and chloroplasts. This review provides an overview of the structural features of outer membrane import receptors that recognize targeting signals. Finally, we briefly discuss combinatorial approaches that might aid in understanding the structural factors mediating receptor targeting signal recognition. PMID- 26365799 TI - Structural Basis of Telomerase Inhibition by the Highly Specific BIBR1532. AB - BIBR1532 is a highly specific telomerase inhibitor, although the molecular basis for inhibition is unknown. Here we present the crystal structure of BIBR1532 bound to Tribolium castaneum catalytic subunit of telomerase (tcTERT). BIBR1532 binds to a conserved hydrophobic pocket (FVYL motif) on the outer surface of the thumb domain. The FVYL motif is near TRBD residues that bind the activation domain (CR4/5) of hTER. RNA binding assays show that the human TERT (hTERT) thumb domain binds the P6.1 stem loop of CR4/5 in vitro. hTERT mutations of the FVYL pocket alter wild-type CR4/5 binding and cause telomere attrition in cells. Furthermore, the hTERT FVYL mutations V1025F, N1028H, and V1090M are implicated in dyskeratosis congenita and aplastic anemia, further supporting the biological and clinical relevance of this novel motif. We propose that CR4/5 contacts with the telomerase thumb domain contribute to telomerase ribonucleoprotein assembly and promote enzymatic activity. PMID- 26365800 TI - Experimental Protein Structure Verification by Scoring with a Single, Unassigned NMR Spectrum. AB - Standard methods for de novo protein structure determination by nuclear magnetic resonance (NMR) require time-consuming data collection and interpretation efforts. Here we present a qualitatively distinct and novel approach, called Comparative, Objective Measurement of Protein Architectures by Scoring Shifts (COMPASS), which identifies the best structures from a set of structural models by numerical comparison with a single, unassigned 2D (13)C-(13)C NMR spectrum containing backbone and side-chain aliphatic signals. COMPASS does not require resonance assignments. It is particularly well suited for interpretation of magic angle spinning solid-state NMR spectra, but also applicable to solution NMR spectra. We demonstrate COMPASS with experimental data from four proteins--GB1, ubiquitin, DsbA, and the extracellular domain of human tissue factor--and with reconstructed spectra from 11 additional proteins. For all these proteins, with molecular mass up to 25 kDa, COMPASS distinguished the correct fold, most often within 1.5 A root-mean-square deviation of the reference structure. PMID- 26365801 TI - Structural Basis for a Novel Interaction between the NS1 Protein Derived from the 1918 Influenza Virus and RIG-I. AB - The influenza non-structural protein 1 (NS1) plays a critical role in antagonizing the innate immune response to infection. One interaction that facilitates this function is between NS1 and RIG-I, one of the main sensors of influenza virus infection. While NS1 and RIG-I are known to interact, it is currently unclear whether this interaction is direct or if it is mediated by other biomolecules. Here we demonstrate a direct, strain-dependent interaction between the NS1 RNA binding domain (NS1(RBD)) of the influenza A/Brevig Mission/1918 H1N1 (1918(H1N1)) virus and the second caspase activation and recruitment domain of RIG-I. Solving the solution structure of the 1918(H1N1) NS1(RBD) revealed features in a functionally novel region that may facilitate the observed interaction. The biophysical and structural data herein suggest a possible mechanism by which strain-specific differences in NS1 modulate influenza virulence. PMID- 26365803 TI - The Neuronal Migration Factor srGAP2 Achieves Specificity in Ligand Binding through a Two-Component Molecular Mechanism. AB - srGAP proteins regulate cell migration and morphogenesis by shaping the structure and dynamics of the cytoskeleton and membranes. First discovered as intracellular effectors for the Robo1 axon-guidance receptor, srGAPs were later identified as interacting with several other nuclear and cytoplasmic proteins. In all these cases, the srGAP SH3 domain mediates protein-protein interactions by recognizing a short proline-rich segment on the cognate-binding partner. However, as interactions between the isolated SH3 domain and a selected set of ligands show weak affinity and low specificity, it is not clear how srGAPs are precisely recruited to their signaling sites. Here, we report a two-component molecular mechanism that regulates ligand binding to srGAP2 by on the one hand dramatically tightening their association and on the other, moderately autoinhibiting and restricting binding. Our results allow the design of point mutations for better probing of srGAP2 activities, and may facilitate the identification of new srGAP2 ligands. PMID- 26365802 TI - Molecular Basis for Cooperative Binding of Anionic Phospholipids to the PH Domain of the Arf GAP ASAP1. AB - We have defined the molecular basis for association of the PH domain of the Arf GAP ASAP1 with phospholipid bilayers. Structures of the unliganded and dibutyryl PtdIns(4,5)P2-bound PH domain were solved. PtdIns(4,5)P2 made contact with both a canonical site (C site) and an atypical site (A site). We hypothesized cooperative binding of PtdIns(4,5)P2 to the C site and a nonspecific anionic phospholipid to the A site. PtdIns(4,5)P2 dependence of binding to large unilamellar vesicles and GAP activity was sigmoidal, consistent with cooperative sites. In contrast, PtdIns(4,5)P2 binding to the PH domain of PLC delta1 was hyperbolic. Mutation of amino acids in either the C or A site resulted in decreased PtdIns(4,5)P2-dependent binding to vesicles and decreased GAP activity. The results support the idea of cooperative phospholipid binding to the C and A sites of the PH domain of ASAP1. We propose that the mechanism underlies rapid switching between active and inactive ASAP1. PMID- 26365804 TI - A spatial epidemic model for disease spread over a heterogeneous spatial support. AB - Data from the Iowa mumps epidemic of 2006 were collected on a spatial lattice over a regular temporal interval. Without access to a person-to-person contact graph, it is sensible to analyze these data as homogenous within each areal unit and to use the spatial graph to derive a contact structure. The spatio-temporal partition is fine, and the counts of new infections at each location at each time are sparse. Therefore, we propose a spatial compartmental epidemic model with general latent time distributions (spatial PS SEIR) that is capable of smoothing the contact structure, while accounting for spatial heterogeneity in the mixing process between locations. Because the model is an extension of the PS SEIR model, it simultaneously handles non-exponentially distributed latent and infectious time distributions. The analysis within focuses on the progression of the disease over both space and time while assessing the impact of a large proportion of the infected people dispersing at the same time because of spring break and the impact of public awareness on the spread of the mumps epidemic. We found that the effect of spring break increased the mixing rate in the population and that the spatial transmission of the disease spreads across multiple conduits. PMID- 26365805 TI - TUR-PSO: A cross-sectional, study investigating quality of life and treatment status of psoriasis patients in Turkey. AB - Psoriasis is a common inflammatory disease that has a severe impact on quality of life. There is lack of data regarding epidemiological and clinical features of psoriasis patients in Turkey, a country with a population of 76 million. The aim of this study was to define the demographic and clinical characteristics, quality of life and treatment patterns of psoriasis patients in Turkey. A cross-sectional observational study was conducted at 40 centers, chosen from geographically diverse locations in Turkey. Patients diagnosed with psoriasis were assessed by investigators who were specialists of dermatology using standardized study questionnaire forms. Dermatology Life Quality Index (DLQI) and EuroQol-5 dimension (EQ-5D) forms were also filled out by each patient. 3971 psoriasis patients were included in this study. 24.2% of plaque psoriasis patients had moderate to severe psoriasis (Psoriasis Area and Severity Index, >=10). Mean DLQI was 7.03 +/- 6.02; quality of life was moderately, severely or very severely affected in 49.2% of patients. The most severely affected component of EQ-5D was anxiety/depression. Among all patients, 22.9% were not receiving any treatment, 39.8% were receiving only topical treatment, 11.5% were on phototherapy, 26.1%, were taking conventional systemic agents and 4.1% were on a biologic treatment. 31.3% of psoriasis patients with moderate to severe disease were treated with only topical agents and only 30.5% of moderate to severe psoriasis patients were receiving systemic therapy. Moderate to severe psoriasis has a considerable impact on quality of life. Treatment in Turkey of patients with moderate to severe psoriasis is insufficient. PMID- 26365806 TI - Arteriosclerosis: facts and fancy. AB - Arterial vascular diseases comprise the leading cause of death in the industrialized world. Every physician learns about the pathology of these diseases in medical school. All pathologists evaluate arterial disease in surgical pathology and/or autopsy specimens. All clinicians encounter patients with clinical manifestations of these diseases. With such a common and clinically important group of entities one would think there would be a general understanding of the "known" information that exists. That is, physicians and scientists should be able to separate what is fact and what is fancy. This review article is intended to generate thought in this regard. PMID- 26365808 TI - Fetal cardiac axis in non-anomalous pregnancies: does fetal gender or maternal body mass index (BMI) matter? AB - OBJECTIVES: To determine if cardiac axis obtained at an early ultrasound study (11-15 weeks) differs from that obtained at a late ultrasound study (18-22 weeks) in the same fetus and to evaluate the impact of fetal gender and/or maternal body mass index (BMI). METHODS: Cardiac axes of 324 non-anomalous fetuses at 11-15 weeks gestation were measured, with follow-up measurements obtained at 18-22 weeks. Comparisons were performed based on gestational age period, fetal gender and obese/non-obese maternal status. RESULTS: (1) Mean fetal cardiac axis did not change between 11 and 15 weeks; p = 0.8, (2) mean fetal cardiac axis was more levorotated at 11-15 weeks than measurements obtained at 18-22 weeks; 48.1 +/- 7.1 degrees versus 43.7 +/- 8.9 degrees ; p < 0.0001, (3) male fetuses had less levorotated cardiac axis than female fetuses in late ultrasound studies but there was no difference between them at early ultrasound studies; 18-22 weeks male fetus, 42.7 +/- 9.3 degrees versus female fetus, 45.2 +/- 8.3 degrees ; p = 0.02 and 11-15 weeks male fetus, 48.1 +/- 7.0 degrees versus female fetus, 48.4 +/- 7.4 degrees , p = 0.7, respectively, and (4) similar trends with the overall study population were observed in the comparison between fetuses of obese and non obese women. CONCLUSION: Fetal cardiac axis remains stable at 11-15 weeks, becoming less levorotated at 18-22 weeks. This may be attributed to increments in fetal lung volume. The differences in cardiac axis measurements between male and female fetuses examined at 18-22 weeks may also be attributable to differences in increment of fetal lung volume during this gestational age period. PMID- 26365807 TI - Continuous vagal nerve stimulation affects atrial neural remodeling and reduces atrial fibrillation inducibility in rabbits. AB - BACKGROUND: The effects of continuous vagal nerve stimulation (VNS) on atrial neural remodeling during atrial fibrillation (AF) remain unclear. OBJECTIVE: To test the hypothesis that VNS affects atrial neural remodeling and reduces AF inducibility. METHODS: Twenty rabbits were randomly divided into two groups: rapid atrial pacing (RAP) group and RAP with VNS group. AF inducibility studies and atrial histologic analyses were performed after 4 weeks. RESULTS: Five rabbits of RAP group (5/10) in the RAP group developed sustained AF. None of rabbits in RAP with VNS group had developed AF. The incidence of sustained AF in VNS group was significant lower than that in rapid pacing group (P<.01). Treatment with VNS resulted in a significant reduction in atrial neural remodeling and AF duration (P<.01). CONCLUSIONS: Atrial neural remodeling plays an important role in the initiation and maintenance of AF. Modulating autonomic nerve function with VNS can contribute to AF control. PMID- 26365809 TI - Metal-free oxidative cleavage of the C-C bond in alpha-hydroxy-beta oxophosphonates. AB - The potential of TBHP to promote oxidative hydroxylation of alpha-hydroxy-beta oxophosphonates (HOPs) through C(CO)-C bond cleavage is described. This cleavage, as depicted in the mechanism is expected through an isomer of HOP that reacts with TBHP to generate acids. PMID- 26365810 TI - The making of an embryo in a basal metazoan: Proteomic analysis in the sea anemone Nematostella vectensis. AB - Cnidarians are widely distributed basal metazoans that play an important role in the marine ecosystem. Their genetic diversity and dispersal depends on successful oogenesis, fertilization and embryogenesis. To understand the processes that lead to successful embryogenesis in these basal organisms, we conducted comparative proteomics on the model sea anemone Nematostella vectensis. We examined four developmental stages from oocyte maturation through early embryogenesis, as well as the oocyte jelly sac in which fertilization and embryogenesis take place. Our analysis revealed 37 stage-specifically expressed proteins, including cell cycle, cellular energy related and DNA replication proteins and transcription regulators. Using in situ hybridization, we show that within the mesenteria, two cell types support successful oocyte development and embryogenesis. Large somatic supporting cells synthesize vitellogenin, the most abundant egg yolk protein within the oocyte, whereas mesenteria gland cells synthesize mucin 5B, which was found to be the main component of the jelly sac. These findings shed light on the sexual reproduction program in cnidarians and suggest a high conservation with proteins governing oogenesis in Bilateria. PMID- 26365811 TI - Overview of antimicrobial options for Mycoplasma pneumoniae pneumonia: focus on macrolide resistance. AB - BACKGROUND AND AIMS: Community-acquired pneumonia (CAP) is a common infectious disease affecting children and adults of any age. Mycoplasma pneumoniae has emerged as leading causative agent of CAP in some region, and the abrupt increasing resistance to macrolide that widely used for management of M. pneumoniae has reached to the level that it often leads to treatment failures. OBJECTIVE: We aim to discuss the drivers for development of macrolide-resistant M. pneumoniae, antimicrobial stewardship and also the potential treatment options for patients infected with macrolide-resistant M. pneumonia. METHODS: The articles in English and Chinese published in Pubmed and in Asian medical journals were selected for the review. RESULTS: M. pneumoniae can develop macrolide resistance by point mutations in the 23S rRNA gene. Inappropriate and overuse of macrolides for respiratory tract infections may induce the resistance rapidly. A number of countries have introduced the stewardship program for restricting the use of macrolide. Tetracyclines and fluoroquinolones are highly effective for macrolide-resistant strains, which may be the substitute in the region of high prevalence of macrolide-resistant M. pneumoniae. CONCLUSION: The problem of macrolide resistant M. pneumonia is emerging. Antibiotic stewardship is needed to inhibit the inappropriate use of macrolide and new antibiotics with a more acceptable safety profile for all ages need to be explored. PMID- 26365812 TI - 'You need to have some guts to teach': Teacher preparation and characteristics for the teaching of sexuality and HIV/AIDS education in South African schools. AB - Using in-depth interviews, we asked sexuality educators in South Africa about their own professional preparation and what they believed were necessary educator characteristics for teaching Sexuality Education. Our findings show that our teachers taught Sexuality Education without any appropriate qualification or preparation, but because they had a lighter teaching load and had room to take on more teaching hours. Nevertheless, they all mention that 'not anybody can teach Sexuality Education'. Drawing on Shulman's taxonomy of knowledge and Freire's concept of critical consciousness, we attempt to make meaning of the teachers' responses and their relevance for the teaching of Sexuality Education. PMID- 26365813 TI - Maternal anxiety and fetal movement patterns in late pregnancy. AB - OBJECTIVE: To determine whether maternal anxiety affects fetal movement patterns in the third trimester of pregnancy. METHODS: The inclusion criteria were a state of good health and a singleton pregnancy between 36 and 40 weeks. Thirty healthy pregnant women were included. The Beck Anxiety Inventory (BA) questionnaire with 21 self-reported items validated for the Brazilian population was applied. The women were asked to record the number of minutes taken to perceive 10 fetal movements once a day for one week. Anxiety symptoms were rated as moderate or severe according to the BAI total score. RESULTS: The mean BAI score was 20.8 (SD = 10.2) and the mean time to count 10 fetal movements was 24.3 min (SD = 6.6 min). The BAI items significantly associated with moderate or severe maternal anxiety were numbness or tingling, fear of the worst happening, terrified, feeling of choking, fear of losing control and fear of dying. There was a statistically significant negative correlation between the total BAI score and the mean time of 10 perceived fetal movements (p < 0.0001; rho = -0.70; 95% CI for rho -0.84 to -0.45). CONCLUSIONS: Maternal anxiety seems to affect fetal movement patterns in late pregnancy and is associated with the mother's increased perception of fetal activity. PMID- 26365814 TI - Characterization of selenium in UO2 spent nuclear fuel by micro X-ray absorption spectroscopy and its thermodynamic stability. AB - Direct disposal of spent nuclear fuel (SNF) in deep geological formations is the preferred option for the final storage of nuclear waste in many countries. In order to assess to which extent radionuclides could be released to the environment, it is of great importance to understand how they are chemically bound in the waste matrix. This is particularly important for long-lived radionuclides such as (79)Se, (129)I, (14)C or (36)Cl, which form poorly sorbing anionic species in water and therefore migrate without significant retardation through argillaceous repository materials and host rocks. We present here X-ray absorption spectroscopic data providing evidence that in the investigated SNF samples selenium is directly bound to U atoms as Se(-II) (selenide) ion, probably replacing oxygen in the cubic UO2 lattice. This result is corroborated by a simple thermodynamic analysis, showing that selenide is the stable form of Se under reactor operation conditions. Because selenide is almost insoluble in water, our data indirectly explain the unexpectedly low release of Se in short term aqueous leaching experiments, compared to iodine or cesium. These results have a direct impact on safety analyses for potential nuclear waste repository sites, as they justify assuming a small fractional release of selenium in performance assessment calculations. PMID- 26365816 TI - There are no caterpillars in a wicked forest. AB - Species trees represent the historical divergences of populations or species, while gene trees trace the ancestry of individual gene copies sampled within those populations. In cases involving rapid speciation, gene trees with topologies that differ from that of the species tree can be most probable under the standard multispecies coalescent model, making species tree inference more difficult. Such anomalous gene trees are not well understood except for some small cases. In this work, we establish one constraint that applies to trees of any size: gene trees with "caterpillar" topologies cannot be anomalous. The proof of this involves a new combinatorial object, called a population history, which keeps track of the number of coalescent events in each ancestral population. PMID- 26365815 TI - Freezing of Fresh Wharton's Jelly From Human Umbilical Cords Yields High Post Thaw Mesenchymal Stem Cell Numbers for Cell-Based Therapies. AB - Some cord blood banks freeze entire pieces of UC (mixed cord, MC) which after post-thaw yields mixed heterogeneous populations of mesenchymal stem cells (MSCs) from all its microanatomical compartments. Freezing of such entire tissues results in sub-optimal post-thaw cell recovery because of poor cryoprotectant diffusion and intracellular ice-formation, heat and water transport issues, and damage to intercellular junctions. To develop a simple method of harvesting pure homogeneous MSCs for cord blood banks, we compared the post-thaw behavior of three groups of frozen UC tissues: (i) freshly harvested WJ without cell separation; (ii) MSCs isolated from WJ (WJSC); and (iii) MC, WJ, and WJSC produced high post-thaw cell survival rates (93.52 +/- 6.12% to 90.83 +/- 4.51%) and epithelioid monolayers within 24 h in primary culture whereas post-thaw MC explants showed slow growth with mixed epithelioid and fibroblastic cell outgrowths after several days. Viability and proliferation rates of post-thawed WJ and hWJSC were significantly greater than MC. Post-thaw WJ and WJSC produced significantly greater CD24(+) and CD108(+) fluorescence intensities and significantly lower CD40(+) contaminants. Post-thaw WJ and WJSC produced significantly lesser annexin-V-positive and sub-G1 cells and greater degrees of osteogenic and chondrogenic differentiation compared to MC. qRT-PCR analysis of post-thaw MC showed significant decreases in anti-apoptotic gene expression (SURVIVIN, BCL2) and increases in pro-apoptotic (BAX) and cell cycle regulator genes (P53, P21, ROCK 1) compared to WJ and WJSC. We conclude that freezing of fresh WJ is a simple and reliable method of generating large numbers of clinically utilizable MSCs for cell-based therapies. PMID- 26365817 TI - Flavonoid Fraction of Citrus reticulata Juice Reduces Proliferation and Migration of Anaplastic Thyroid Carcinoma Cells. AB - Effects of flavonoids extracted from Citrus reticulata (mandarin) juice on proliferation and migration of 3 human anaplastic thyroid carcinoma (ATC) cell lines were evaluated. Flavonoid components of Mandarin juice extract (MJe) were analyzed by uHPLC. Proliferation of CAL-62, C-643, and 8505C cells, measured by 3 (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, was significantly reduced by MJe in a concentration- and time-dependent way, with maximal effect elicited at 0.5 mg/ml concentration after 48 h. Cytofluorimetric analysis showed a block in the G2/M phase of the cell cycle, accompanied by low cell mortality owed to autophagic death. The extract caused also a reduction of cell migration, associated with decreased activity of the metalloproteinase MMP-2. These findings demonstrate that the flavonoid fraction of mandarin juice exerts in vitro antiproliferative effects on ATC cells, associated with a reduction of migration, suggesting for such a functional food a potential use as adjuvant in the treatment of thyroid cancer. PMID- 26365818 TI - Spirometry in children with asthma and/or allergic rhinitis: comparison of FEF25 75% with the standard measures. AB - AIM: Forced expiratory flow between 25%and75% of vital capacity (FEF25-75%), a spirometric measure of small airways, may predict the presence of airway responsiveness both in asthmatics and in allergic rhinitics. We aimed to search the correlation between FEF25-75% and standard measures of spirometry (FEV1% and FEV1/FVC) in different clinical conditions, that is in children with asthma, in children with asthma and allergic rhinitis, in children with allergic rhinitis and in healthy children METHODS: Children with asthma(n=116), asthma plus allergic rhinitis(n=25), allergic rhinitis(n=75) and healthy controls(n=52) were evaluated. Clinical examinations, spirometry and bronchodilation tests were performed. RESULTS: In asthmatics there was a strong correlation between FEF25 75% and FEV1%(r=0.596, p<0.001); and between FEF25-75% and FEV1/FVC(r=0.740, p<0.001). In AR patients correlation between FEF25-75% and FEV1%(r=0.367, p=0.001); and between FEF25-75% and FEV1/FVC(r=0.534, p<0.001) were less prominent compared to asthmatics but they were still significant and strong. In children with both allergic rhinitis (AR) and asthma correlation between FEF25 75% and FEV1%(r=0.633, p=0.001) and between FEF25-75% and FEV1/FVC(r=0.539, p=0.005) were again significant. Pre-test FEV1% and FEF25-75% in AR patients were lower than that of the control subjects. After the bronchodilation, percentage change in the FEV1 in AR patients were significantly higher then the control subjects(p=0.010). AR patients showed significant increases in FEV1%, (p<0.001), FEF25-75%, (p<0.001) and , (p=0.001) after the bronchodilation test. Within the AR patients only 12/75(16.0%) showed bronchodilation with salbutamol. Among the ones with a FEF25-75% <65% FEV1% was normal in 6/43 (14%) patients in asthmatics and FEV1% was normal in 3/9 (33%) patients in asthma +AR patients. CONCLUSION: Besides the FEV1% and FEV1/FVC, the FEF25-75% may be a useful and early spirometric parameter to evaluate the children with asthma and or AR. PMID- 26365819 TI - Serial elongation derotation flexion (EDF) casting for patients with infantile and juvenile scoliosis. AB - Infantile and juvenile scoliosis, among different types of spinal deformity, is still a challenge for pediatric orthopedic surgeons. The ideal treatment of infantile and juvenile scoliosis has not yet been identified as both clinicians and surgeons still face multiple challenges, including preservation of the thoracic spine, thoracic cage, lung growth and cardiac function without reducing spinal motion. Elongation, derotation, flexion (EDF) casting technique is a custom-made thoracolumbar cast based on a three dimensional correction concept. This cast offers three-dimensional correction and can control the evolution of the deformity in some cases. Spinal growth can be guided by EDF casting as it can influence the initially curved spine to grow straighter. This article aimed to provide a comprehensive review of how infantile and juvenile scoliosis can affect normal spine and thorax and how these deformities can be treated with serial EDF casting technique. A current literature review is mandatory in order to understand the principles of the serial EDF casting technique and the effectiveness of conservative treatment in young and very young patients. PMID- 26365820 TI - Evaluation of physical activity and dietary behaviors in young athletes: a pilot study. AB - BACKGROUND: The aim of this study was to evaluate the lifestyle based on the physical activity and eating habits of young athletes. METHODS: In order to measure physical activity and eating habits in young people, 922 young athletes between the ages of 8 to 18 have been analyzed in this study. The participants were all patients come to our Department for sport eligibility evaluation; we have asked them to complete an accurate questionnaire in order to assess their personal physical activity levels and their regular eating habits. Parents were invited to sign a letter explaining the aims of the study and were asked for permission on behalf of their child to take part on the study. RESULTS: The eating habits and the physical activity levels of the young athletes observed, resulted improper. We have noticed that the 13.7% of the participants were overweight and obese, despite their practiced sport activity. Physical activity, without sport activity, resulted inadequate in 38.6% of participants: they did not practice regular physical activity. CONCLUSIONS: The results of the study clearly indicate that higher education is therefore necessary in order to promote a healthy lifestyle in terms of both eating habits and physical activity not only in young people, but also in parents and coaches of teams. PMID- 26365821 TI - Congenital pulmonary airway malformations: from prenatal diagnosis to postnatal outcome. AB - Congenital pulmonary airway malformations (CPAMs) include cystic and non-cystic lung lesions. These represent about 30-40% of developmental lung bud anomaly lesions mainly diagnosed during pregnancy or in newborn infants; or sometimes they remain undetected until adult life. The malformation usually presents as a sporadic, non-hereditary lung abnormality, with no predilection for the right or left lung, sex or race. CPAMs vary in their histological features, epidemiological and clinical presentation, severity and prognosis, supporting the embryologic hypothesis of arrested lung growth during branching morphogenesis. The existence of "hybrid" forms underline the possible common pathogenic mechanism involved in the development of different lesion types; a genetic role has also been proposed in abnormal lung development. Influence of the natural history on pre and postnatal management is relevant. Surgical resection is the standard of therapy for symptomatic CPAMs, while the management of asymptomatic cases remains controversial. The potential risk of infection and malignancy in CPAMs justifies complete surgical resection in the first year of life; while long term follow-up is required in children who do not undergo surgery. A multidisciplinary team including gynecologists, neonatologists, radiologists, pediatricians and pediatric surgeons is recommended in pre, postnatal management and in the postsurgical follow-up of all children with CPAMs. PMID- 26365823 TI - The effect of vitamin D auxiliary rehabilitation therapy in children with cerebral palsy and language dysfunction. AB - OBJECTIVE: To observe the clinical efficacy of vitamin D auxiliary rehabilitation therapy in children with cerebral palsy and language dysfunction. METHODS: Eighty two cases of children with cerebral palsy and language dysfunction in our hospital from March 2011 to June 2014 were selected for this study. They were divided into two groups: the rehabilitation treatment group (simple group, 39 cases) and the vitamin D auxiliary rehabilitation therapy group (combination group, 43 cases). After three months of treatment, language development, Gesell Child Development Scale, Bayley Infant Development Scale score and vitamin D and calcium levels were compared. RESULTS: The language development, Gesell Child Development Scale, Bayley Infant Development Scale score and vitamin D and calcium levels for two of the groups, after treatment, are improved compared to before treatment. The difference was statistically significant (P < 0.05). The total efficiency of the language development in the combination group was obviously higher than the simple group. The difference was significant (95.3% vs. 74.4%, X2 = 2.486, P = 0.032). The Gesell Child Development Scale improved in the combination group compared to the simple group. The difference was statistically significant [(70.4 +/- 11.3) vs (53.3 +/-10.5), t = 3.127, P = 0.026]. The proportion of normal children was significantly higher than the rehabilitation treatment group, and the difference was statistically significant (30.2% vs. 20.5%, X2 = 3.016, P = 0.029). In the combination group, the vitamin D and calcium levels were statistically increased compared to the rehabilitation treatment group. It had statistical differences between the two groups (P<0.05). CONCLUSION: Vitamin D auxiliary rehabilitation therapy could improve the language function and the language development status in children with cerebral palsy and language dysfunction. PMID- 26365822 TI - Inter- and intra-rater reliability of nasal auscultation in daycare children. AB - BACKGROUND: The aim of this study was to assess nasal auscultation's intra- and inter-rater reliability and to analyze ear and respiratory clinical condition according to nasal auscultation. METHODS: Cross-sectional study performed in 125 children aged up to 3 years old attending daycare centers. Nasal auscultation, tympanometry and Paediatric Respiratory Severity Score (PRSS) were applied to all children. Nasal sounds were classified by an expert panel in order to determine nasal auscultation's intra and inter- rater reliability. The classification of nasal sounds was assessed against tympanometric and PRSS values. RESULTS: Nasal auscultation revealed substantial inter-rater (K=0.75) and intra-rater (K=0.69; K=0.61 and K=0.72) reliability. Children with a "non-obstructed" classification revealed a lower peak pressure (t=-3.599, P<0.001 in left ear; t=-2.258, P=0.026 in right ear) and a higher compliance (t=-2,728, P=0.007 in left ear; t=-3.830. P<0.001 in right ear) in both ears. There was an association between the classification of sounds and tympanogram types in both ears (X=11.437, P=0.003 in left ear; X=13.535, P=0.001 in right ear). Children with a "non-obstructed" classification had a healthier respiratory condition. CONCLUSIONS: Nasal auscultation revealed substantial intra- and inter-rater reliability. Nasal auscultation exhibited important differences according to ear and respiratory clinical conditions. Nasal auscultation in pediatrics seems to be an original topic as well as a simple method that can be used to identify early signs of nasopharyngeal obstruction. PMID- 26365824 TI - Analysis of the clinical diagnosis data of four experimental detection methods for pediatric syphilis. AB - OBJECTIVE: To analyze the clinical testing data of syphilis suspected children, to give more comprehensive detection information and offer experimental basis for the clinical diagnosis of syphilis. METHODS: From April 2010 to December 2012, 141 suspected syphilis children, 0-3 years old in XuZhou Children's Hospital were selected and divided into two groups: infants group (0-<1 years old, 119 cases) and children group (1-3 years old, 22 cases). Blood samples were collected from these children and following experimental detection methods were used: the rapid plasma reagin (RPR) test, the colloidal gold test (SYP), the enzyme-linked immuno sorbent assay (ELISA) and the Treponema pallidum particle agglutination (TPPA) test. The relevant experimental data were analyzed by SPSS 13.0 software. RESULTS: The positive rate of ELISA was the highest, RPR was the lowest; the positive rate of SYP and TPPA were higher than RPR, the positive rate of SYP and TPPA were lower than ELISA, and the differences were statistically significant. Among the 86 false positives, the rate for ELISA was the highest, and no TPPA false positive was found. False positive were higher in the children group than the infant group. CONCLUSION: High false positive rate of ELISA could be caused by hemolysis. RPR had low sensitivity in suspected syphilis neonates, and SYP was suitable for emergency treatment. TPPA was fit for the diagnosis of syphilis. Thus a combination of all these methods would be the best choice to cure syphilis infection in children. Final diagnosis can only be confirmed after periodically reexamining samples of suspected syphilis children. PMID- 26365825 TI - Gene transfer on inorganic/organic hybrid silica nanosheets. AB - Gene delivery is often accomplished by the forward or reverse transfection protocol. In either protocol, a transfection reagent (usually cationic) is added to increase the delivery efficiency. In this study, we employed a series of nanosheet networks to facilitate the delivery of naked plasmid DNA into human mesenchymal stem cells (hMSCs). By adding different chemicals into the reaction mixture for etching the silica glass, we were able to fabricate inorganic/organic hybrid nanosheet networks with different physico-chemical characteristics. We then analyzed the transfection efficiency on different nanosheets and the possible dependence of the transfection efficiency on the physico-chemical parameters of nanosheets. The results showed that all nanosheet networks were noncytotoxic and demonstrated a high cell survival rate (~90%) after transfection. The transfection efficiency was critically determined by the aspect ratio (height/thickness of the wall) of the nanosheets. The effects of chemistry or other surface properties were not significant. Moreover, the transfection efficiency may be successfully predicted by the initial cell migration rate and the activation of integrin beta3 on the nanosheets. Compared to the conventional method, transfection using concurrent cell/plasmid seeding on the nanosheets is not only more effective but also much safer. Future efforts may focus on combining the inorganic/organic hybrid nanosheets with soft substrates for in situ transfection. PMID- 26365826 TI - Point-prevalence surveillance of healthcare-associated infections in Swedish hospitals, 2008-2014. Description of the method and reliability of results. AB - BACKGROUND: In 2007 the Swedish Association of Local Authorities and Regions (SALAR) decided to establish a nationwide system for point-prevalence surveillance of healthcare-associated infections (HCAIs) among hospitalized patients. Surveillance started in 2008 and has since then been performed twice a year (April and October). The documentation of HCAIs is performed by regular clinical physicians and nurses on each hospital ward aided by oral and written instructions. All Swedish publicly financed hospitals (>95% of all hospitals) are included (25,862 beds in 2008 and 24,905 beds in 2013). A total of 88-92% of all inpatients has been covered in each survey. The overall prevalence of HCAI (including psychiatric inpatients) has ranged from 7.8% to 10.0%. AIM: In 2012 SALAR decided to assess the reliability of the prevalence data. METHODS: In all, 1216 patients were assessed for HCAIs by both the regular surveillance teams and teams with expert knowledge on HCAI independently of each other. FINDINGS: The prevalence of HCAI was 8.3% (95% confidence interval: 6.7-9.9) according to the regular teams and 13.1% (11.2-15.0) according to the expert teams. The sensitivity of the regular point-prevalence surveillance was 47% and the specificity 97%. CONCLUSION: The Swedish system for repeated nationwide point prevalence surveillance of HCAI has had a high coverage of about 90% since it commenced. However, the surveys underestimate the true prevalence of HCAI. PMID- 26365827 TI - Risk of organism acquisition from prior room occupants: a systematic review and meta-analysis. AB - A systematic review and meta-analysis was conducted to determine the risk of pathogen acquisition for patients associated with prior room occupancy. The analysis was also broadened to examine any differences in acquisition risk between Gram-positive and Gram-negative organisms. A search using Medline/PubMed, Cochrane and CINHAL yielded 2577 citations between 1984 and 2014. Reviews were assessed in accordance with the international prospective register of systematic reviews (PROSPERO). Just seven articles met the inclusion criteria, namely: (a) papers were peer reviewed, (b) pathogen acquisition prevalence rates were reported, (c) articles were written in English; and (d) had minimal or no risk of bias based on the Newcastle-Ottawa Scale (NOS). One study was an extension of a previous study and was discarded. Employing NOS provided little difference between the studies, with five studies receiving eight-star and two studies receiving seven-star ratings, respectively. Overall, pooled acquisition odds ratio for study pathogens (meticillin-resistant Staphylococcus aureus; vancomycin resistant enterococcus; Clostridium difficile; acinetobacter; extended-spectrum beta-lactamase-producing coliforms; pseudomonas) was 2.14 [95% confidence interval (CI): 1.65-2.77]. When comparing data between Gram-positive and Gram negative organisms, the pooled acquisition odds ratio for Gram-negatives was 2.65 (95% CI: 2.02-3.47) and 1.89 (95% CI: 1.62-2.21) for Gram positives. The findings have important implications for infection control professionals, environmental cleaning services and patients, since current practices fail to adequately reduce acquisition risk. Although there may be non-preventable sources of acquisition, revised practices require collaborative work between all responsible staff in order to reduce this risk to a minimum. PMID- 26365829 TI - Can Diet Prevent Breast Cancer? PMID- 26365828 TI - Interrogation of the intersubunit interface of the open Hv1 proton channel with a probe of allosteric coupling. AB - The Hv1 voltage-gated proton channel is a dimeric complex consisting of two voltage-sensing domains (VSDs), each containing a gated proton permeation pathway. Dimerization is controlled by a cytoplasmic coiled-coil domain. The transitions from the closed to the open state in the two VSDs are known to occur cooperatively; however, the underlying mechanism is poorly understood. Intersubunit interfaces play a critical role in allosteric processes; but, such interfaces have not been determined in the open Hv1 channel. Here we show that 2 guanidinothiazole derivatives block the two Hv1 VSDs in a cooperative way, and use one of the compounds as a probe of allosteric coupling between open subunits. We find that the extracellular ends of the first transmembrane segments of the VSDs form the intersubunit interface that mediates coupling between binding sites, while the coiled-coil domain does not directly participate in the process. We also find strong evidence that the channel's proton selectivity filter controls blocker binding cooperativity. PMID- 26365830 TI - Anticoagulant flavonoid oligomers from the rhizomes of Alpinia platychilus. AB - Two pairs of enantiomers of flavonoid oligomers (1a and 1b, 2a and 2b) along with one known chalcone (3) were isolated from the rhizomes of Alpinia platychilus. Their structures were elucidated on the basis of spectroscopic data (MS and 1D/2D NMR). The absolute configurations of the flavonoid oligomers were established by their ECD spectra. Separation of the enantiomeric mixtures (1a and 1b, 2a and 2b) was achieved on a chiral column using hexane:isopropyl alcohol:ethanol (7:2:1) as eluents. The anticoagulant assay showed that 2a, 2b and 3 exhibited potent activities to prolong the prothrombin times (PT) and the thrombin times (TT). PMID- 26365831 TI - Prenylated phenylpropanoid compounds from the stem bark of Illicium burmanicum. AB - Ten new prenylated phenylpropanoid compounds, burmanicumols A-G (1-6) and illifrognones D-G (7-10), and seven known prenylated phenylpropanoid compounds, were isolated from the stem bark of Illicium burmanicum. The structures of the new compounds were determined on the basis of 1D and 2D NMR, HRESIMS, and CD experiments. Compounds 3, 8, 10, and 14 were moderately potent inhibitors of the NF-kappaB pathway, with IC50 values ranging from 10.31 to 35.16MUg/mL tripterygium glycosides and pavlin were used as the positive controls. PMID- 26365832 TI - Thrombus Characteristics Are Related to Collaterals and Angioarchitecture in Acute Stroke. AB - BACKGROUND: We have theorized that clots with stasis are longer. We therefore explored the relationship between thrombus imaging characteristics on noncontrast computed tomography (NCCT) and magnetic resonance imaging (MRI) with clot length and pial collaterals on baseline computed tomography angiography (CTA). METHODS: Prospective study of acute ischemic stroke patients (2005-2009) from Keimyung University. Patients with known stroke symptom onset time, baseline CTA, MRI, and with M1-Middle Cerebral Artery (MCA)+/-intracranial internal carotid artery (ICA) occlusions were included. Clot length and pial collaterals were measured on baseline CTA. RESULTS: A total of 104 patients (mean age 65.1+/-12.28 years, 56.7% male, median baseline National Institutes of Health Stroke Scale 13) with intracranial ICA + MCA (n=50) or isolated M1-MCA (n=54) occlusions were included. Hyperdense sign on NCCT had a median clot length of 42.3 mm versus 29.5 mm when hyperdense negative (p=0.02). Clots showing blooming artifact on gradient recall echo MRI had a median length of 39.1 mm versus 24.5 mm without blooming (p=0.005). Patients with poor baseline collaterals on CTA had longer clots than those with intermediate/good collaterals (median clot length 49.4 mm vs 34.9 mm vs 20.5 mm respectively, p<0.001). In censored logistic regression modeling, clot length was an independent predictor of hyperdense sign (p=0.05) and of the presence of blooming artifact (p=0.006). CONCLUSIONS: Clot length and baseline collateral status are independent predictors of clot hyperdensity on NCCT and blooming artifact on gradient recall echo. Longer clots are more likely to be hyperdense and to bloom more, probably because portions of these clots are freshly formed locally due to of stasis of blood around the original clot. This stasis could be because of poor collaterals and inefficient angio-architecture within the cerebral arterial tree. PMID- 26365833 TI - Dantrolene an unusual option for detrusor overactivity: observations of a patient with cerebral palsy. AB - We report a case of a 49-year-old female with cerebral palsy with spastic tri plegia and lumbar spondyolisthesis diagnosed to have overactive neurogenic bladder, which improved on treatment with Dantrolene along with antimuscarinics. She was initially treated with antimuscarinics both transdermal and oral simultaneously and later received intravesical OnaBotulinum toxinA. Following lumbar spine fixation for spondylolisthesis, her bowel and bladder function deteriorated and she was commenced on Dantrolene for her spasticity, along with being on Oxybutinin and Mirabegron. This significantly improved her symptoms. Overactive bladder symptoms are a common manifestation in cases of CP. In refractory cases where antimuscarinics and intravesical botulinum toxin therapy have failed, a combination of Dantrolene with antimuscarinics and/or beta 3 receptor agonists may prove to be beneficial. While on therapy, regular monitoring of liver functions is required to promptly diagnose and treat hepatotoxicity. PMID- 26365834 TI - Colorimetric and fluorescence detection of G-quadruplex nucleic acids with a coumarin-benzothiazole probe. AB - A colorimetric and red-emitting fluorescent dual probe for G-quadruplexes was devised with a conjugated coumarin-benzothiazole scaffold. Its significant and distinct changes in both color and fluorescence enable the label-free and visual detection of G-quadruplex structures. In addition, this probe gives a distinct strong emission response to the nucleoli in fixed cells imaging, which might be attributed to the interaction between the probe and rDNA G-quadruplex based on the chromatin immunoprecipitation assay. All these results suggest its promising application prospects in the G-quadruplex research field. PMID- 26365836 TI - A Longitudinal Study of Medical Practices' Treatment of Patients Who Use Tobacco. AB - INTRODUCTION: Many patients who use tobacco have never been encouraged by their healthcare providers to quit. In recent years, incentives have been provided for medical practices to incorporate tobacco-cessation processes into routine care. This study examined growth in use of these processes as well as organizational and policy factors associated with their implementation. METHODS: Data from three National Study of Physician Organizations surveys fielded in 2006-2013 were analyzed in 2014. The analyses estimated multivariate longitudinal and cross sectional linear regression models to assess the relationship between implementation of cessation processes and change in practices' characteristics and external incentives, including state mandates for tobacco-cessation coverage. RESULTS: Systematic identification of patients who use tobacco increased in large (26% to 91%, p<0.0001) and small-medium practices (69% to 83%, p<0.0001). Neither routine advice to quit nor referral to counseling and guideline-based point-of care reminders increased. Practice feedback to physicians on their use of cessation interventions increased (18% to 29%, p<0.0001) for small-medium practices. State-mandated coverage was associated with the use of cessation processes in small-medium practices (p<0.0001), as was pay for performance participation (p<0.0001); public reporting (p<0.0001); Medicaid revenue (p=0.02); and practice size (p<0.0001). Among large practices, predictors were practice size (p<0.0001); hospital ownership (p=0.004); public reporting (p=0.03); and primary care practice (p=0.04). CONCLUSIONS: The findings suggest that state mandated coverage for tobacco-cessation treatment and increased use of external incentives such as pay for performance and public reporting programs may improve care for patients who use tobacco. PMID- 26365835 TI - Extracellular DNA facilitates the formation of functional amyloids in Staphylococcus aureus biofilms. AB - Persistent staphylococcal infections often involve surface-associated communities called biofilms. Staphylococcus aureus biofilm development is mediated by the co ordinated production of the biofilm matrix, which can be composed of polysaccharides, extracellular DNA (eDNA) and proteins including amyloid fibers. The nature of the interactions between matrix components, and how these interactions contribute to the formation of matrix, remain unclear. Here we show that the presence of eDNA in S. aureus biofilms promotes the formation of amyloid fibers. Conditions or mutants that do not generate eDNA result in lack of amyloids during biofilm growth despite the amyloidogeneic subunits, phenol soluble modulin peptides, being produced. In vitro studies revealed that the presence of DNA promotes amyloid formation by PSM peptides. Thus, this work exposes a previously unacknowledged interaction between biofilm matrix components that furthers our understanding of functional amyloid formation and S. aureus biofilm biology. PMID- 26365837 TI - Divergent marijuana trajectories among men: Socioeconomic, relationship, and life satisfaction outcomes in the mid-30s. AB - BACKGROUND: Given recent changes in marijuana policy in the United States, it is important to understand the long-term effects of marijuana use on adult functioning. We examined whether men who displayed different trajectories of marijuana use from adolescence through emerging adulthood (age ~15-26) differed in terms of socioeconomic, social, and life satisfaction outcomes in their mid 30s. METHODS: Data came from a longitudinal sample of men who were recruited in early adolescence (N=506) and followed into adulthood. Four trajectory groups based on patterns of marijuana use from adolescence into emerging adulthood were compared on adult outcomes (age ~36) before and after controlling for co occurring use of other substances and several pre-existing confounding factors in early adolescence. The potential moderating effect of race was also examined. RESULTS: Although there were initially group differences across all domains, once pre-existing confounds and co-occurring other substance use were included in the model, groups only differed in terms of partner and friend marijuana use. Chronic marijuana users reported the highest proportions of both. Frequent and persistent marijuana use was associated with lower socioeconomic status (SES) for Black men only. CONCLUSIONS: After statistically accounting for confounding variables, chronic marijuana users were not at a heightened risk for maladjustment in adulthood except for lower SES among Black men. Chronic users were more likely to have friends and partners who also used marijuana. Future studies should take into account pre-existing differences when examining outcomes of marijuana use. PMID- 26365839 TI - Hearing loss in New Zealand-planning for the future. PMID- 26365838 TI - Solitary cannabis use in adolescence as a correlate and predictor of cannabis problems. AB - BACKGROUND: Most adolescent cannabis use occurs in social settings among peers. Solitary cannabis use during adolescence may represent an informative divergence from normative behavior with important implications for understanding risk for cannabis problems. This longitudinal study examined associations of adolescent solitary cannabis use with levels of cannabis use and problems in adolescence and in young adulthood. METHODS: Cannabis using-adolescents aged 12-18 were recruited from clinical programs (n=354; 43.8% female; 83.3% Caucasian) and community sources (n=93; 52.7% female; 80.6% Caucasian). Participants reported on cannabis use patterns and diagnostic symptoms at baseline and multiple follow-ups into young adulthood. RESULTS: Compared to social-only users, adolescent solitary cannabis users were more likely to be male and reported more frequent cannabis use and more DSM-IV cannabis use disorder (CUD) symptoms. Regression analyses showed that solitary cannabis use in adolescence predicted CUD symptom counts in young adulthood (age 25) after controlling for demographic variables and the frequency of adolescent cannabis use. However, solitary adolescent cannabis use was no longer predictive of age 25 CUD symptoms after additionally controlling for adolescent CUD symptoms. CONCLUSIONS: Solitary cannabis use is associated with greater cannabis use and problems during adolescence, but evidence is mixed that it predicts young adult cannabis problems. PMID- 26365840 TI - Recent changes in the management of aortic dissection. PMID- 26365841 TI - The projected burden of hearing loss in New Zealand (2011-2061) and the implications for the hearing health workforce. AB - BACKGROUND: There is considerable evidence that New Zealand's population is ageing. For example, the median age increased from 29 years in 1951 to 37 years in 2011-12, and will likely increase to 44 years by 2061. While the implications of an ageing population have been studied, to date there is no study investigating the impacts that population ageing will have on hearing health in New Zealand. AIM: To explore the changing population structure and estimate the burden of hearing loss in New Zealand between 2011 and 2061. METHODS: Using three alternative population projections from Statistics New Zealand, we quantify the likely distribution of the population between 2011 and 2061 by age and sex. Published estimates of hearing loss stratified by age and severity of hearing loss were then applied to the population projections to highlight the potential impact that population ageing will have on hearing loss in New Zealand in the next 50 years. RESULTS: We estimated that there were 330,269 people aged >=14 years with hearing loss and this would increase to 449,453 in 2061. Overall, males have a higher prevalence of hearing loss than females, and while the prevalence of hearing loss among those aged 14-49 years is expected to decrease, the prevalence among the population aged >=70 years is expected to double between 2011 and 2061. CONCLUSION: Age, sex and geographical variations in hearing loss are expected in the next 50 years. Further research into ethnic and variations in hearing loss will be instrumental in targeting the future hearing health workforce required to accommodate these increases. PMID- 26365842 TI - The sharp end of cardiovascular disease in New Zealand: A review of acute type A aortic dissections of the Waikato. AB - AIM: Acute type A aortic dissections are lethal cardiovascular surgical emergencies. This study is a retrospective comparative review of mortality in Type A aortic dissections between Maori and non-Maori populations of the Midland DHBs catchment area. METHOD: 143 patients identified with diagnosis of type A aortic dissections at Waikato Hospital from 1990 to 2013, as identified in Waikato Hospital clinical records and cardiothoracic surgery database. The Maori and non-Maori populations were compared according to demographics, 30-day survival and 5-year survival. RESULT: The overall 30-day mortality rate of 28% was consistent with published international data, but there were significant ethnic and gender disparities related to the high prevalence of cardiovascular risk factors, particularly in the Maori population. Maori have a significantly higher prevalence of type A aortic dissections (2.5 per 10,000) compared to non Maori (1.4 per 10,000) and have a 5-year earlier mean age at presentation compared to non-Maori. Maori females have the highest mortality rates with almost half succumbing within 30 days of surgery (45.5%). CONCLUSION: The future promises an increasing incidence of acute type A aortic dissections in a younger Maori population with severe disease burden and less reserve, as well as in an elderly population where age is an independent predictor of worse operative mortality, morbidity and reduced long-term survival. GP and specialist collaborative directions are identified towards evolution of surgery and systems to maintain, if not improve, early and late survival rates in the Midland DHBs catchment region. PMID- 26365843 TI - Treatment of octogenarians with lung cancer: A single centre audit of treatments and outcomes. AB - AIMS: Document the incidence, stage at presentation and therapy offered to octogenarians with non-small cell lung cancer (NSCLC) over 3 years and compare to those under 80 years old. METHODS: A retrospective analysis of patients with NSCLC managed via a lung cancer multidisciplinary team at Canterbury District Health Board. Follow-up data at one year following presentation was analysed. RESULTS: The study population comprised 124 octogenarians (mean 83.7 years), of whom 54 (42%) were female. Participants presented with adenocarcinoma 48 (38.7%), squamous cell 35 (28.2%) and without tissue diagnoses 41 (33.1%). Stage I and II lung cancer was found in 43 (34%) patients. Surgical resection ensued in six (4.8%), radiotherapy with curative intent in 20 (16.1%), non-curative treatment options in 98 (79%), compared to 106 (15.4%), 112 (15.6%) and 431 (67.2%) respectively of the 635 patients in the under 80 group with NSCLC. All of the surgical group and 15 (75%) in the radiotherapy group of octogenarians were alive at one year; which is comparable to the rest of the cohort, where all patients of the surgical group and 63 (64.2%) of the radiotherapy group were alive at one year. CONCLUSION: Octogenarians who undergo radiotherapy or surgery with curative intent have an excellent one year survival. Because all patients were alive at one year following surgical resection, we conclude that surgery seems to be a viable treatment option in octogenarians, which may be underutilised. PMID- 26365844 TI - New Zealand's neurologist workforce: a pragmatic analysis of demand, supply and future projections. AB - AIMS: To estimate current and future specialist neurologist demand and supply to assist with health sector planning. METHODS: Current demand for the neurology workforce in New Zealand was assessed using neuroepidemiological data. To assess current supply, all New Zealand neurology departments were surveyed to determine current workforce and estimate average neurologist productivity. Projections were made based on current neurologists anticipated retirement rates and addition of new neurologists based on current training positions. We explored several models to address the supply-demand gap. RESULTS: The current supply of neurologists in New Zealand is 36 full-time equivalents (FTE), insufficient to meet current demand of 74 FTE. Demand will grow over time and if status quo is maintained the gap will widen. CONCLUSIONS: Pressures on healthcare dollars are ever increasing and we cannot expect to address the identified service gap by immediately doubling the number of neurologists. Instead we propose a 12-year strategic approach with investments to enhance service productivity, strengthen collaborative efforts between specialists and general service providers, moderately increase the number of neurologists and neurology training positions, and develop highly skilled non-specialists including trained. PMID- 26365845 TI - A lack of anaesthetic clinical attachments for emergency medicine advanced trainees in New Zealand: perceptions of directors of emergency medicine training. AB - AIMS: Anaesthetic skills are a core competency for emergency physicians. Anecdotally, there are limited anaesthetic attachments specifically available for Emergency Medicine Advanced Trainees (ATs). This study had several aims: Firstly, to quantify anaesthetic terms set aside for ATs; secondly, to gauge the opinions of Directors of Emergency Medicine Training (DEMTs) regarding the importance and difficulty in securing and maintaining anaesthetic training terms for ATs in their institutions; thirdly, to outline strategies that DEMTs used to get or maintain these posts and their opinions about what institutions should do to provide anaesthetic training for ATs. METHODS: An online qualitative survey was emailed to all DEMTs of hospitals accredited for vocational ED training within New Zealand. Registered Medical Officer (RMO) units at accredited hospitals were asked to provide numbers of anaesthetic places available specifically for ATs. RESULTS: Annually there are 15 anaesthetic training posts set aside for 145 ATs. Most DEMTs thought that an anaesthetic term was important for progression of vocational training, and a majority thought that term availability was a significant barrier to progression of training. A number of DEMTs felt that procuring and maintaining anaesthetic posts was difficult, some citing a lack of collegiality from anaesthetic departments. Some DEMTs and ATs used novel approaches to procure anaesthetic attachments. CONCLUSIONS: Anaesthetic skills are an essential component of emergency medicine vocational training. It is in the best interests of hospitals to provide anaesthetic training positions for ATs. There are few training positions currently available. PMID- 26365846 TI - The role of medical generalism in the New Zealand health system into the future. AB - New Zealand hospitals are facing medical workforce shortages and an ageing population with increasing multimorbidity. To be sustainable in the future, the future medical workforce will need expertise in dealing with the complexity of people living with multiple physical and mental health issues. This will require a greater focus on generalism within the speciality colleges, and generalist doctors within the hospital settings, as well as their traditional home of community settings. Doctors' career choices will need to be matched to changing community need. The Transalpine Health Services generalist, specialist and sub specialist workforce model developed by the West Coast and Canterbury health systems points the way to future sustainable provision of a quality patient hospital experience as close to home as possible, for people who live in provincial New Zealand, through a regional network approach. System-wide changes are suggested to support a more balanced future medical workforce. These include greater valuing of careers in generalism, aligning of incentives to promote medical careers based in generalism, developing regional networks that cross existing District Health Board boundaries to provide patient care, and application of system outcome metrics that measure quality of care and patient outcomes in an integrated health system. PMID- 26365847 TI - Meeting the challenges of interpreting variants of unknown clinical significance in BRCA testing. AB - Many BRCA1 and BRCA2 genetic mutations are known to result in an elevated breast cancer risk. Routine BRCA1/2 gene screening is offered to patients thought to have an increased risk of carrying a deleterious mutation. 5-10% of genetic tests identify a variant of unknown clinical significance (VUCS), creating significant challenges to health care providers. Recent advances in sequencing technologies allow more genes to be screened in an increasing number of individuals and at an ever decreasing cost. Significantly more VUCS will be identified, adding to the uncertainty of how to manage these patients. The addition of splicing assays to current variant classification tools may be instrumental towards understanding the disease risk of these variants and improve the reliability of these assays. PMID- 26365848 TI - Huge palatal mass. PMID- 26365849 TI - May we at least have a civilised discussion about primary aldosteronism in New Zealand? PMID- 26365850 TI - Age-related changes of nasal cavity and conchae volumes and volume fractions in children: a stereological study. AB - BACKGROUND: The anatomy of the human nasal cavity (NC) is complex and its structures are closely related to the functions of the NC. Studies which assessing the mean volumes of NC and conchae are very infrequent. The purpose of current study is to investigate development of NC and conchae according to age and sex by using stereological method. MATERIALS AND METHODS: This retrospective volumetric study was carried out on 342 individuals (166 females and 176 males) between 0 and 18 years old with no pathological conditions or medical procedures that affected the skeletal morphology of the NC. Volumetric estimations were determined on computed tomography (CT) images using point-counting approach of stereological methods. RESULTS: NC, inferior nasal conchae (INC) and middle nasal conchae (MNC) volume measurements that obtained using point-counting method were increased with age in both sexes until 15 years old. Regardless of gender; no significant difference was determined between the left and right values for NC, conchae volumes and choanae measurements. Generally, significant differences were determined in NC and INC volumes according to gender after they reached maximum growth period. According to age the volume ratios of INC to NC and MNC to NC were ranged from 18% to 32% and 9% to15%, respectively. CONCLUSIONS: The current study demonstrated that the point-counting method is effective in determining volume estimation of NC and is well suited for CT studies. Our results could provide volumetric indexes for the NC and conchae, which could help the physician for both patient selections for surgery, and for the assessment of any surgical technique used to treatment of nasal obstruction. (. PMID- 26365851 TI - Symmetrical anatomical variant of the anterior belly of the digastric muscle: clinical implicat. AB - The digastric muscle is an important surgical landmark. Several anatomical variants of the digastric muscle are reported in literature and, in particular, the presence of accessory anterior bellies of the muscle is not uncommon. Here, an unreported symmetrical variant of the digastric muscle was found during a dissection of the suprahyoid region. The dissection showed digastric muscles with an accessory anterior belly, which originated from the anterior belly of muscles in proximity and anteriorly to the intermediate tendon. The accessory bellies were fused together on the midline and were attached with a unique tendon to the inner surface of the mental symphysis. These muscles completely filled the submental triangle. This unreported anatomical variant could be considered an additional contribution to description of the anatomical variants of the digastric muscle, with several implications in head and neck pathology, diagnosis and surgery. PMID- 26365852 TI - Does allicin combined with vitamin B-complex have superior potentials than alpha tocopherol alone in ameliorating lead acetate-induced Purkinje cell alterations in rats? An immunohistochemical and ultrastructural study. AB - BACKGROUND: The current article aims to explore the protective potentials of alpha-tocopherol alone and the combination of allicin and vitamin B-complex against lead-acetate neurotoxicity on the cerebellar cortex. MATERIALS AND METHODS: Forty rats were divided into four groups (n = 10). Group 1 was the control group; Group 2 received 10 mg/kg body weight (BW) of lead acetate; Group 3 was exposed to 10 mg/kg BW of lead acetate plus a combination of allicin (100 mg/kg BW) and vitamin B-complex (40 mg/kg BW); Group 4 was administered lead acetate (10 mg/kg BW) and alpha-tocopherol (100 mg/kg BW). The animals received the treatment for 60 days by oral gavage. All the groups were studied ultrastructurally and immunohistochemically with glial fibrillary acidic protein (GFAP). RESULTS: The affected groups revealed shrunken and degenerated Purkinje cells with irregular nuclei. The cytoplasm comprised several lysosomes, unhealthy mitochondria, and dilated Golgi saccules. The myelinated nerve fibres demonstrated breaking of the myelin sheaths, apparent vacuoles, and broad axonal spaces. Immunohistochemically, there was a tremendous surge in GFAP-positive astrocytes in the lead acetate-treated group. These histological and ultrastructural variations were ameliorated by the administration of a-tocopherol and the combination of allicin and vitamin B complex. Moreover, an apparent decrease in the number of GFAP-positive astrocytes was obvious in the protected groups. CONCLUSIONS: Although both a-tocopherol and the combination of allicin and vitamin B-complex can be used as possible adjuvant therapies to ameliorate nervous system ailments attributable to lead acetate, alpha-tocopherol showed more protective potential. PMID- 26365853 TI - A study concerning morphometry of abdominal aorta branches and abdominal viscera: relations and correlation. AB - Research interest on abdominal aorta branches and abdominal viscera morphometry is renewed by technological evolution and development of new radiologic and clinical applications including stent grafts and chemoembolisation materials. Despite that, data on morphometry of abdominal aorta branches and abdominal viscera are lacking. To investigate this subject authors performed a morphometric study on 50 adult fresh and embalmed Caucasian cadavers and examined abdominal aorta branches', kidney and spleen morphometry. Our results on arteries' morphometry did not differ significantly from those of the literature; yet, we discovered significant differences between fresh and embalmed cadavers on viscera morphometry, spleen and kidneys. We also found previously unreported correlations between abdominal aorta branches' morphometric characteristics. Even more, we identified correlations between regional arteries and viscera morphometric characteristics, proposing a new factor determining viscera development. Finally, we performed an extensive literature review so to place our results in an anatomic, embryologic and, even more, a clinical context. We believe that our results add knowledge on abdominal aorta branches and viscera morphometry and are valuable for clinical, radiological and surgical applications including visceral arteries' aneurysms investigation and treatment, chemoembolisation procedures, stent grafts design and transplantation. PMID- 26365854 TI - A rare variation of the incomplete coeliac trunk. AB - During the routine dissection course, we found a rare variation of the incomplete coeliac trunk in an 87-year-old Korean male cadaver. The left gastric artery, the splenic artery and the hepatomesenteric trunk arose independently from the abdominal aorta. The detailed branching pattern of this case could not be classified by classic classification systems, but belongs to type III' of Morita's classification. The accurate embryological knowledge on the arterial variations is important both to anatomists and to clinicians. PMID- 26365855 TI - Suprascapular foramen: a rare variation caused by ossified suprascapular ligaments. AB - BACKGROUND: The aim of this study was to investigate the incidence of the suprascapular foramen in West Anatolian population. MATERIALS AND METHODS: Eighty one dried human scapulae of West Anatolian people of unknown ages and gender belonging to the Anatomy Department Laboratory of Dokuz Eylul University Medical School were examined macroscopically. The vertical and transverse diameters of the suprascapular foramen and central thickness of the ossified ligaments were measured with calliper in millimetres and digital calliper, respectively. RESULTS: We observed the suprascapular foramen due to ossification of the suprascapular ligament only in 2 of 81 (2.47%) scapulae. The vertical and transverse diameters of the suprascapular foramen and central thickness of the ossified ligaments (No. 1 and No. 2) were measured as 8.0 mm vs. 4.0 mm, 3.6 mm vs. 2.0 mm and 4.0 mm vs. 1.4 mm, respectively. CONCLUSIONS: The suprascapular foramen caused by ossified suprascapular ligament is rarely observed variation in West Anatolian population. PMID- 26365856 TI - A computed tomography study on the correlation between the morphometry of the suprascapular notch and anthropometric measurements of the scapula. AB - BACKGROUND: The suprascapular notch is a clinically important site because it is the main site of injury and compression of the suprascapular nerve. Its shape and size are the most important factors in the aetiopathology of suprascapular nerve neuropathy. This article reports the first computed topography (CT) study on the correlation between the diameters of the suprascapular notch and anthropometric measurements of the human scapula. MATERIALS AND METHODS: A total of 130 scans of shoulders by a helical 32-row multidetector CT scanner were retrospectively analysed. The following scapular measurements were performed: morphological length, morphological width, projection length of the scapular spine, maximal width of the scapular spine, length of the acromion, maximal length of the coracoid process, length of the superior border of the scapula, morphological height of the supraspinous fossa, length of the lateral border of the scapula, and morphological height of infraspinous fossa. The following suprascapular notch dimensions were measured: maximal depth, superior transverse diameter, middle transverse diameter. RESULTS: The maximum depth of the suprascapular notch correlates with the morphological length of the scapula, the length of the lateral border of the scapula and the morphological width of the scapula. The superior transverse diameter of the suprascapular notch correlates with the length of the superior border of the scapula and negatively with the length of the lateral border of the scapula. In addition it has been shown that the length of the superior border of the scapula correlates more closely with the superior transverse diameter of the suprascapular notch than the middle transverse diameter of the suprascapular notch. CONCLUSIONS: It could be supposed that humans with longer scapulae have deeper notches. It may be also concluded that scapulae with a wider superior border have a shallower suprascapular notch. PMID- 26365857 TI - Rabbit common calcanean tendon as an animal model: ultrasonographic anatomy and morphometry. AB - BACKGROUND: The aim of the present study was to evaluate usefulness of ultrasonography in assessment of rabbit common calcanean tendon, to describe its ultrasonographic anatomy and to perform morphometric analysis of this structure. MATERIALS AND METHODS: Fifteen skeletally-matured New Zealand rabbits were used in the study. Ultrasonographic examinations of common calcanean tendon (CCT) were performed in longitudinal and transverse planes from caudal approach. Sagittal diameters of superficial digital flexor tendon and CCT were measured on longitudinal scans. Sagittal and transverse diameter, cross-sectional area and perimeter of the CCT were assessed on transverse scans. Statistical analysis was performed using StatisticaPL software (StatSoft(r), Poland). RESULTS: In longitudinal images structure of CCT was clearly visualised. Its superficial hypoechoic part corresponds to superficial digital flexor tendon and deeper hyperechoic to gastrocnemius tendon. In transverse images cross-sectional area presented varied echotexture. Proximally, CCT was rounded in transverse section and became slightly wider and flattered distally. Statistical analysis showed no differences between results obtained from right and left hindlimb (p > 0.05). Measurements of sagittal diameter of CCT obtained in transverse planes were significantly higher than sagittal diameter measurements obtained in longitudinal plane in corresponding locations (p < 0.001). All performed measurements showed a growing trend with the increasing distance from the calcaneal tuber. CONCLUSIONS: Ultrasonography is suitable technique for assessment of CCT in a rabbit model and provides satisfactory images for morphometrical evaluation. PMID- 26365858 TI - Uncommon branching pattern of the hepatic arteries in a living donor: a case report and brief literature review. AB - Numerous variations of the hepatic arteries are common in surgical patients. We present a 35-year-old woman who was admitted to our department in order to assess possibility of becoming living donor. Preoperative computed tomography scan revealed anomalous branching pattern of the hepatic arteries. In this case right posterior sectoral artery has been given off by the greater pancreatic artery, left hepatic artery has been replaced by the artery arising from the left gastric artery and double segment 4 branches have been observed. To the best of our knowledge, this pattern has not been described in the literature, yet. PMID- 26365859 TI - Morphological predictors of sleep apnoea severity. AB - BACKGROUND: Obstructive sleep apnoea (OSA) does not always depend on obesity but on a certain morphological configuration. The study objective was to verify a hypothesis about a relation between anthropometric features and OSA occurrence and severity. MATERIALS AND METHODS: The study involved 138 patients, who had reported in Department and Clinic of Otolaryngology, Warsaw Medical University, due to suspected OSA. Each patient underwent morphological evaluation according to visual analogue scales. The assessment involved nasal septum morphology evaluation according to a 4-grade scale, palate morphology evaluation according to the 4-grade Friedman scale, whereas the facial profile, oropharyngeal isthmus, and the shape of the nasopharynx were assessed according to our own 3-grade scale. RESULTS: Statistical analysis confirmed the high concordance of the basic polysomnographic parameters with the Friedman scale and the shape of the oropharyngeal isthmus. CONCLUSIONS: 1. The modified Mallampati score as well as evaluation of the shape of the oropharyngeal isthmus demonstrated high concordance with the basic polysomnographic parameters. 2. The neck circumference is a significant predictor of the apnoea-hypopnoea index value in males suffering from the OSA syndrome. PMID- 26365860 TI - Early postnatal development of the lumbar vertebrae in male Wistar rats: double staining and digital radiological studies. AB - The aim of the study was to evaluate the physiological developmental changes of male rats' lumbar vertebrae during the first 22 days after birth. Morphology and mineralisation of lumbar vertebrae were evaluated using double-staining and digital radiography system, which allowed vertebral width and optical density to be determined. Pup weight, crown-rump length, body mass index and vertebral width increased during postnatal period and significantly correlated with their age. Bone mineralisation, as measured by optical density, did not show any significant differences. The complete fusion of the primary ossification centres had a cranio -caudal direction and started on day 19 after parturition but was incomplete by day 22. It could be concluded that, unlike significant age-related increase of vertebral size, mineralisation was only slightly elevated during evaluated postnatal period. The method described is supplementary to alizarin red S staining as it provides both qualitative and quantitative data on mineralisation in a similar manner to micro computed tomography but does not allow 3 dimensional and microarchitecture examination. PMID- 26365861 TI - Comparative anatomical study of standard percutaneous and modified medialised percutaneous Bunnell type repair for artificial Achilles tendon rupture: positive effect of medialisation of the stitches with lower risk of sural nerve injury. AB - BACKGROUND: Less invasive percutaneous acute Achilles tendon rupture (AATR) repair techniques gain popularity because of lower risk of surgical wound complications. But these approaches have an increased risk of sural nerve iatrogenic injury as this sensory nerve is usually not visualised during minimally invasive operative procedures. We compared standard percutaneous Bunnell type and our proposed modified-medialised percutaneous technique in a cadaver study to evaluate potential advantages. MATERIALS AND METHODS: Ten pairs of fresh frozen specimens were divided into two groups for comparative anatomical study. Tenotomies of Achilles tendons were made and wounds sutured. Ten standard and 10 modified-medialised repairs were applied for artificially performed ruptures. All sutured tendons were dissected meticulously. We carefully looked at repaired Achilles tendon end-to-end contact and adaptation, distance from Achilles insertion in calcaneal tubercle to place where sural nerve crosses lateral border of the Achilles tendon and possible sural nerve and vein entrapment. Groups were compared using Fisher's exact and Student-T tests. RESULTS: All ends of sharply dissected tendons in both groups were in sufficient contact. No measurable diastasis between tendon ends was found in all cases. No entrapment of sural nerve or vein was found in modified percutaneous Bunnell suture technique group, whereas 7 of 10 sural nerves and 9 small saphenous veins were entrapped when using standard percutaneous Bunnell type technique. Average distance from Achilles tendon insertion in tuber calcanei to sural nerve crossing the lateral border of Achilles was 93 mm. CONCLUSIONS: Medialisation of percutaneous suture in AATR repair shows clear advantages compared to standard non medialised technique ensuring a possible lower incidence of sural nerve entrapment injury. Our modified percutaneous Bunnell type technique allows sufficient adaptation of ruptured Achilles tendon. PMID- 26365862 TI - Butterfly vertebra. A case report and a short review of the literature. AB - A butterfly vertebra is a rare congenital anomaly, encountered as isolated finding or as part of syndromic diseases. We report a case of a 40-year- old female presenting with low back pain and sciatica due to 'butterfly' dysplasia of the first sacral vertebra. This novel case includes posterolateral displacement of the completely separated hemivertebrae, causing left lateral recess stenosis and compression of S1 nerve root. Additionally, we conducted a short review of the literature. Few cases are reported in literature. Only one refers to a sacral vertebra. There is no previous case of a butterfly vertebra that accounts for narrowing of the lateral recess and associated radiculopathy. PMID- 26365863 TI - Prevalence of generalised joint hypermobility in school-aged children from east central European region. AB - BACKGROUND: There is no literature regarding joint mobility in children of the Central and Eastern Europe. Studies describing clinical characteristics and functional outcomes are still needed. The aim of this study was to assess the prevalence of generalised joint hypermobility (GJH) in the group of school-aged children from Vilnius, the capital city of Lithuania, in relation to different cut-off values of the Beighton score (BS), and to identify possible patients with joint hypermobility syndrome. MATERIALS AND METHODS: The representative sample of this study was calculated to be 760 subjects. A total of 778 children from different schools were screened for the mobility of joints. The medical examination included an assessment of joints' hypermobility according to the BS. The presence of specific signs (marfanoid habitus, antimongoloid slant and drooping eyelids) was assessed additionally. Parents of all involved children were asked to answer the questions developed based on the Brighton criteria regarding the medical history of children. RESULTS: The prevalence of GJH in school-aged children from Vilnius, depending on the BS cut-off value, was 19.2% (BS >= 4), 9.5% (BS >= 5) or 5.7% (BS >= 6). The increased range of mobility was most frequently detected in thumbs of school- -aged children. The frequency of hyperextension > 10o in knees was 7- to 8-fold lower than the frequency of hyperextension > 10o in a passive opposition of the thumb. The evaluation results were similar on the left and right sides in 87.4% cases of thumb opposition, 90.1% cases of hyperextension of 5th finger, 87.9% cases of elbow manoeuvres, and 94.8% attempts to hyperextend knee. CONCLUSIONS: The prevalence of GJH in school aged children from Vilnius depends on the BS cut-off value and ranges from 5.7% to 19.2%. PMID- 26365864 TI - A rare case of dual origin of the left vertebral artery without convergence. AB - A case of dual origin of the left vertebral artery was encountered in a dissection course for medical students in 2014. Two vertebral arteries were observed on the left side. One arose from the aortic arch between the origin of the left common carotid artery and the left subclavian artery, entered the transverse foramen of the 4th cervical vertebra, and coursed upward into the transverse foramen. The other arose from the left subclavian artery as expected, divided into two branches anterior to the cervical vertebrae, and entered the transverse foramina of the 6th and 7th cervical vertebrae. Both branches flowed into the anterior spinal artery. Moreover, as seen in other anomalies, 3 arterial fenestrations were observed in the cranial arteries. This case is extremely unique with respect to the following points: the 2 ipsilateral vertebral arteries did not combine to form 1 vertebral artery, the vertebral artery of subclavian artery origin entered the transverse foramen of the 7th cervical vertebra, and 3 fenestrations were observed in the intracranial arteries. This is a very suggestive case for neurosurgeons and radiologists who perform treatments involving the vertebral artery. PMID- 26365865 TI - Vascular anatomical features of the medial thigh flap in human cadavers of Caucasian origin. AB - BACKGROUND: Medial fasciocutaneous flaps, which are based on the femoral artery from the thigh region, are used for wide inguinal, scrotal, vaginal, perineal, leg, head and neck defect reconstructions in injured human patients. Within this regard, anatomical knowledge about perforating and cutaneous branches of the femoral artery is important for the surgeons. MATERIALS AND METHODS: In the present study, vascular pedicles of the medial thigh perforator flap based on the femoral artery were investigated according to anatomical and surgical landmarks. Human Caucasian preserved cadavers of 15 adults (13 males, 2 females; age range 55-82 years: 30 sides, bilaterally) that were previously formalin fixed were subjected to our analytical examinations. Micro dissections were performed under 4* loop magnification while representing the perforating branches of the femoral artery after filling by coloured latex injection via the external iliac artery. RESULTS: The size and length parameters of these branches which appeared around the apex of the femoral triangle were evaluated. The mean size of the perforating branch at the point of origin was 0.14 cm and the mean size of the cutaneous branch at the point of origin was 0.09 cm, the mean length of the pedicle was 4.74 cm and the mean length of the cutaneous branch was 3.30 cm, respectively. Location of the perforating and the cutaneous branches were also determined according to the surgical landmarks such as the anterior superior iliac spine, inguinal ligament, pubic tubercle and interepicondylar line. CONCLUSIONS: The pedicle of the medial flap should locate up to 25 cm from the anterior superior iliac spine so as to preserve the vascular structures. Exact location of this artery helps the surgeons to perform anastomosis in an easier and safer manner during surgical operations. PMID- 26365866 TI - Anatomy of the anteromedial thigh flap based on the oblique branch of the descending branch of the lateral circumflex femoral artery. AB - Anteromedial thigh (AMT) flaps based on lateral circumflex femoral artery (LCFA) have characteristics which make them favourable for use in reconstruction of extensive thigh, head, neck and leg defects. AMT flap which is elevated on the artery has the advantages of low donor site morbidity and preservation of main arteries. Due to inconstant anatomy of the pedicle, the flap is mostly not preferable. Hence, we aimed to describe the anatomical features of the unnamed branch of the descending branch of the LCFA harvesting AMT flap. For this purpose, the external iliac artery was displayed bilaterally on 15 adult (13 males and 2 females; age range 55-82 years) preserved cadavers using latex injection. The perforator branch of the descending branch from the LCFA was microdissected under 4* loupe magnification. The perforator branch was located 28.53 (20.20-34.20) cm distal to the anterior superior iliac spine, 22.12 (13.40 28.00) cm distal to the pubic tubercle, and 13.20 (10.80-16.20) cm proximal to the interepicondylar line. At the level of origin point the mean diameter of the perforating branch was 0.17 cm and the mean diameter of its cutaneous branch was 0.14 cm. The mean length of the pedicle was 5.71 (3.70-9.00) cm. We conclude that our findings contribute to the literature in terms of anatomical knowledge for surgical safety. PMID- 26365867 TI - Evaluation of vertebral artery dominance, hypoplasia and variations in the origin: angiographic study in 254 patients. AB - BACKGROUND: The aim of this study was to determine the dimensional characteristics and variations in the origin of vertebral arteries (VA). MATERIALS AND METHODS: We retrospectively reviewed angiographic studies in 254 patients (133 males, 121 females) for the evaluation of diameter differences in VA. We examined different criteria from the literature (difference of >= 0.3 mm, >= 0.8 mm, >= 1 mm between the widths of two VA and diameter ratio more than 1.4) to find out the dominant VA, rate of co-dominance and hypoplasia. The differences among groups were analysed using the c2 and Kruskal-Wallis test. Also concordance analysis test was used to determine correspondence between the tests. We also noticed the variations in the origin of VA. RESULTS: The average diameter of VA in 254 patients was 3.21 +/- 0.7 mm on the right, and 3.16 +/- 0.7 mm on the left. The average diameter difference was found 0.88 +/- 0.7 mm. The rate of hypoplasia was found 7.1% on the right and 9.4% on the left. Among 254 patients according to the criterion of any diameter difference; right side was found wider in 126 (49.6%) patients and left side was found wider in 120 (47.2%) patients. The criterion of 0.3 mm or greater difference showed right VA dominance in 107 (42.1%) patients, left VA dominance in 99 (39%) patients. Co-dominance was mainly observed when we used the criteria of 0.8 mm and 1 mm or greater difference and diameter ratio more than 1.4. We found out harmony of two criterion of difference of >= 0.8 mm and >= 1 mm (concordance analysis test, 76.1%). There was no statistically significant relation between age, gender and any dominance criteria (p > 0.05). The majority of VA showed classical origin arising from both subclavian arteries with a rate of 94.9%. CONCLUSIONS: The most striking result we have found is the dominance of the right VA in diameter by using all different criteria unlike with previous reports in the literature. PMID- 26365868 TI - Synthesis, (1)H and (13)C NMR assignment of novel 2-pyridone derivatives. PMID- 26365870 TI - Advances in high-resolution mass spectrometry based on metabolomics studies for food--a review. AB - Food authenticity becomes a necessity for global food policies, since food placed in the market without fail has to be authentic. It has always been a challenge, since in the past minor components, called also markers, have been mainly monitored by chromatographic methods in order to authenticate the food. Nevertheless, nowadays, advanced analytical methods have allowed food fingerprints to be achieved. At the same time they have been also combined with chemometrics, which uses statistical methods in order to verify food and to provide maximum information by analysing chemical data. These sophisticated methods based on different separation techniques or stand alone have been recently coupled to high-resolution mass spectrometry (HRMS) in order to verify the authenticity of food. The new generation of HRMS detectors have experienced significant advances in resolving power, sensitivity, robustness, extended dynamic range, easier mass calibration and tandem mass capabilities, making HRMS more attractive and useful to the food metabolomics community, therefore becoming a reliable tool for food authenticity. The purpose of this review is to summarise and describe the most recent metabolomics approaches in the area of food metabolomics, and to discuss the strengths and drawbacks of the HRMS analytical platforms combined with chemometrics. PMID- 26365869 TI - Putting on the brakes: Bacterial impediment of wound healing. AB - The epithelium provides a crucial barrier to infection, and its integrity requires efficient wound healing. Bacterial cells and secretomes from a subset of tested species of bacteria inhibited human and porcine corneal epithelial cell migration in vitro and ex vivo. Secretomes from 95% of Serratia marcescens, 71% of Pseudomonas aeruginosa, 29% of Staphylococcus aureus strains, and other bacterial species inhibited epithelial cell migration. Migration of human foreskin fibroblasts was also inhibited by S. marcescens secretomes indicating that the effect is not cornea specific. Transposon mutagenesis implicated lipopolysaccharide (LPS) core biosynthetic genes as being required to inhibit corneal epithelial cell migration. LPS depletion of S. marcescens secretomes with polymyxin B agarose rendered secretomes unable to inhibit epithelial cell migration. Purified LPS from S. marcescens, but not from Escherichia coli or S. marcescens strains with mutations in the waaG and waaC genes, inhibited epithelial cell migration in vitro and wound healing ex vivo. Together these data suggest that S. marcescens LPS is sufficient for inhibition of epithelial wound healing. This study presents a novel host-pathogen interaction with implications for infections where bacteria impact wound healing and provides evidence that secreted LPS is a key factor in the inhibitory mechanism. PMID- 26365871 TI - Yttrium-90 microsphere radioembolotherapy in a patient with spontaneously ruptured hepatocellular carcinoma. AB - Spontaneous rupture of hepatocellular carcinoma (HCC) is a potentially fatal presentation of the disease. Although many options for treatment exist, Yttrium 90 transcatheter arterial radioembolization has not previously been reported. We report a case of a 92-year-old woman found to have a ruptured HCC treated with radioembolization that showed no viable tumor and no extrahepatic disease at 2 years. While further studies are warranted, this patient's clinical course may suggest that radioembolization may be an additional palliative treatment option in these patients. PMID- 26365872 TI - Can MRI biomarkers at 3 T identify low-risk ductal carcinoma in situ? AB - OBJECTIVE: The objective was to explore whether 3-T magnetic resonance imaging (MRI) can identify low-risk ductal carcinoma in situ (DCIS). METHODS: Dynamic contrast-enhanced and diffusion-weighted (DWI) MRI features of 36 DCIS lesions [8 low risk, Van Nuys Pathologic Classification (VNPC) 1; 28 high risk, VNPC 2/3] were reviewed. An MRI model that best identified low-risk DCIS was determined using multivariate logistic regression. RESULTS: Low-risk DCIS exhibited different DWI properties [i.e., higher contrast-to-noise ratio (P=.02) and lower normalized apparent diffusion coefficients (P=.04)] than high-risk DCIS. A model combining these DWI features provided best performance (area under receiver operating characteristic curve =0.86). CONCLUSIONS: DWI may help identify DCIS lesions requiring less therapy. PMID- 26365873 TI - Recent development of recycling lead from scrap CRTs: A technological review. AB - Cathode ray tubes (CRTs) contain numerous harmful substances with different functions. Lead is found in the funnel glass of CRTs. Improperly treated toxic lead may pose significant risks to human health and the environment. This paper reviews and summarizes existing technological processes on the recycling of lead from waste CRTs, including pyrometallurgy, hydrometallurgy, and product regeneration. The present situation, advantages, and disadvantages of these techniques are described in detail. Generally, pyrometallurgy shows better practicability in recovery lead from waste CRT than hydrometallurgy and hydrometallurgy, in view of environmental impact, energy-consumption, product formats and safety and maturity of technology. Moreover, the gaps in the existing technologies were identified and recommendations for future research were provided. PMID- 26365874 TI - Cancer arises from stem cells: opportunities for anticancer drug discovery. PMID- 26365875 TI - Oxidation of the alarmin IL-33 regulates ST2-dependent inflammation. AB - In response to infections and irritants, the respiratory epithelium releases the alarmin interleukin (IL)-33 to elicit a rapid immune response. However, little is known about the regulation of IL-33 following its release. Here we report that the biological activity of IL-33 at its receptor ST2 is rapidly terminated in the extracellular environment by the formation of two disulphide bridges, resulting in an extensive conformational change that disrupts the ST2 binding site. Both reduced (active) and disulphide bonded (inactive) forms of IL-33 can be detected in lung lavage samples from mice challenged with Alternaria extract and in sputum from patients with moderate-severe asthma. We propose that this mechanism for the rapid inactivation of secreted IL-33 constitutes a 'molecular clock' that limits the range and duration of ST2-dependent immunological responses to airway stimuli. Other IL-1 family members are also susceptible to cysteine oxidation changes that could regulate their activity and systemic exposure through a similar mechanism. PMID- 26365876 TI - The health of parents with and without intellectual impairment in the UK. AB - BACKGROUND: Little is known about the health and well-being of the 'hidden majority' of parents with mild intellectual disability (ID), who are less likely to be in contact with disability services. METHOD: We sought to add to knowledge in this area by examining the health and living conditions of parents with and without intellectual impairment in a large contemporary nationally representative sample of UK parents aged between 16 and 49 years old (n = 14 371). RESULTS: Our results indicated that, as expected, parents with intellectual impairment were at significantly greater risk than other parents of having poorer self-reported general, mental and physical health. They were also at significantly greater risk of experiencing higher rates of household socio-economic disadvantage and environmental adversities and lower rates of neighbourhood social capital and intergenerational support. Adjusting risk estimates to take account of between group differences in household socio-economic disadvantage eliminated statistically significant differences in health status between parents with and without intellectual impairment on all but one indicator (obesity). Further adjusting risk estimates to take account of between group differences in neighbourhood adversity, neighbourhood social capital and intergenerational support had minimal impact on the results. CONCLUSIONS: That controlling for between-group differences in exposure to socio-economic disadvantage largely eliminated evidence of poorer health among parents with intellectual impairment is consistent with the view that a significant proportion of the poorer health of people with IDs may be attributable to their poorer living conditions rather than biological factors associated with ID per se. PMID- 26365877 TI - Disabling mitochondrial reprogramming in cancer. AB - Recent studies have demonstrated that tumor cells exposed to molecular therapy with PI3K antagonists redistribute their mitochondria to the peripheral cytoskeleton, fueling membrane dynamics, turnover of focal adhesion complexes and increased tumor cell motility and invasion. Although this process paradoxically increases metastatic propensity during molecular therapy, it also emphasizes a critical role of regional mitochondrial bioenergetics in tumor metabolic reprogramming and may offer prime therapeutic opportunities to prevent disseminated disease. PMID- 26365878 TI - Upregulation of the kappa opioidergic system in left ventricular rat myocardium in response to volume overload: Adaptive changes of the cardiac kappa opioid system in heart failure. AB - Opioids have long been known for their analgesic effects and are therefore widely used in anesthesia and intensive care medicine. However, in the last decade research has focused on the opioidergic influence on cardiovascular function. This project thus aimed to detect the precise cellular localization of kappa opioid receptors (KOR) in left ventricular cardiomyocytes and to investigate putative changes in KOR and its endogenous ligand precursor peptide prodynorphin (PDYN) in response to heart failure. After IRB approval, heart failure was induced using a modified infrarenal aortocaval fistula (ACF) in male Wistar rats. All rats of the control and ACF group were characterized by their morphometrics and hemodynamics. In addition, the existence and localization as well as adaptive changes of KOR and PDYN were investigated using radioligand binding, double immunofluorescence confocal analysis, RT-PCR and Western blot. Similar to the brain and spinal cord, [(3)H]U-69593 KOR selective binding sites were detected the left ventricle (LV). KOR colocalized with Cav1.2 of the outer plasma membrane and invaginated T-tubules and intracellular with the ryanodine receptor of the sarcoplasmatic reticulum. Interestingly, KOR could also be detected in mitochondria of rat LV cardiomyocytes. As a consequence of heart failure, KOR and PDYN were up-regulated on the mRNA and protein level in the LV. These findings suggest that the cardiac kappa opioidergic system might modulate rat cardiomyocyte function during heart failure. PMID- 26365879 TI - The genomic landscape of epithelioid sarcoma cell lines and tumours. AB - We carried out whole genome and transcriptome sequencing on four tumour/normal pairs of epithelioid sarcoma. These index cases were supplemented with whole transcriptome sequencing of three additional tumours and three cell lines. Unlike rhabdoid tumour (the other major group of SMARCB1-negative cancers), epithelioid sarcoma shows a complex genome with a higher mutational rate, comparable to that of ovarian carcinoma. Despite this mutational burden, SMARCB1 mutations remain the most frequently recurring event and are probably critical drivers of tumour formation. Several cases show heterozygous SMARCB1 mutations without inactivation of the second allele, and we explore this further in vitro. Finding CDKN2A deletions in our discovery cohort, we evaluated CDKN2A protein expression in a tissue microarray. Six out of 16 cases had lost CDKN2A in greater than or equal to 90% of cells, while the remaining cases had retained the protein. Expression analysis of epithelioid sarcoma cell lines by transcriptome sequencing shows a unique profile that does not cluster with any particular tissue type or with other SWI/SNF-aberrant lines. Evaluation of the levels of members of the SWI/SNF complex other than SMARCB1 revealed that these proteins are expressed as part of a residual complex, similarly to previously studied rhabdoid tumour lines. This residual SWI/SNF is susceptible to synthetic lethality and may therefore indicate a therapeutic opportunity. PMID- 26365880 TI - Questioning the impact of journal impact factor on research? PMID- 26365881 TI - Clinicopathological features of gastric hepatoid adenocarcinoma. PMID- 26365882 TI - Development of a scale to assess children's trust in general nurses. AB - PURPOSE: Develop a Children's Trust in General Nurses Scale (CTGNS). DESIGN AND METHODS: In a cross-sectional investigation, 128 U.K. children (68 females and 60 males; mean age = 10 years and 4 months) completed the CTGNS and reported their trust in, and fear of, nurses. A total of 46 parents reported those dispositions and the frequency of their children visiting medical centres. RESULTS: The CTGNS showed acceptable internal consistency and factor structure. It was correlated with reported children's trust in nurses and visiting medical centres. PRACTICE IMPLICATIONS: The CTGNS will permit the investigation of children's trust in nurses and interventions to promote it. PMID- 26365883 TI - Unraveling of the Effect of Nodose Ganglion Degeneration on the Coronary Artery Vasospasm After Subarachnoid Hemorrhage: An Experimental Study. AB - BACKGROUND: Cardiac arrest is a major life-threatening complication of subarachnoid hemorrhage (SAH). Although medullary cardiocirculatuar center injury and central sympathetic overactivity have been suspected of initiating coronary artery spasm-induced cardiac arrest, we aimed to elucidate the effects of vagal ischemia at the brainstem on coronary vasospasm and sudden death in SAH. METHODS: Twenty-six rabbits were randomly divided into 3 groups. Control (n = 5); SHAM (n = 8), and SAH group (n = 13). Experimental SAH was applied by injecting homologous blood into the cisterna magna, and the SHAM group was injected with isotonic saline solution also in the cisterna magna., Twenty-one days after the injection, histopathologic changes of the neuron density of nodose ganglia, the vasospasm index values of the coronary arteries, and the electrocardiographic events were analyzed. RESULTS: Increased vasospasm index of the coronary arteries and degenerated neuron density of nodose ganglion were significantly different between animals with SAH, control, and SHAM groups (P < 0.005). If neurons of the nodose ganglia are lesioned due to ischemic insult during SAH, the heart rhythm regulation by vagus afferent reflexes is disturbed. CONCLUSIONS: We found that there is causal relationship between nodose ganglion degeneration and coronary vasospasm. Our finding could be the reason that many cardiac events occur in patients with SAH. Vagal pathway paralysis induced by indirect sympathetic overactivity may trigger coronary vasospasm and heart rhythm disturbances. Our findings will aid in the planning of future experimental studies and in determining the clinical relevance of such studies. PMID- 26365884 TI - Intracranial Dislocation of the Mandibular Condyle: A Case Report and Literature Review. AB - BACKGROUND: Intracranial dislocation of the mandibular condyle is an infrequent injury that can follow traumatic upward force at the chin. A limited number of cases have been reported, and an individualized approach for patients is often recommended. Nevertheless, several consistent strategies for reduction have emerged. METHODS: We present the case of a 20-year-old pregnant woman with multiple facial and skeletal injuries who required open reduction after a motor vehicle accident. We also reviewed the English literature for all reported cases of traumatic mandibular dislocation into the middle cranial fossa. The demographics, presentation, surgical approach, and follow-up were examined. RESULTS: A total of 52 cases were identified, with most events occurring in the younger and female population, usually after motor vehicle (54%) or bicycle trauma (25%). At least one neurological finding was reported in 60% of initial presentations. Most reductions required an open procedure (73%), for which either a preauricular or temporal approach was used at comparatively similar rates. Additional condylotomy or condylectomy was sometimes incorporated, but most open reductions were achieved by traction (62%). At follow-up, half of reporting patients noted persistent mandibular deviation and mean maximal opening was 37.7 mm. CONCLUSIONS: Appropriate surgical and nonsurgical approaches for addressing mandibular dislocation have emerged during the past several decades. When deciding on an optimal strategy, variables including patient age, time-to diagnosis, accompanying injuries, prior failed maneuvers, and risk of resubluxation should be considered. Coordinated care between neurosurgery and otolaryngology teams can minimize complications and achieve successful reductions. PMID- 26365885 TI - Impact of Enzymatic and Microbial Bioprocessing on Protein Modification and Nutritional Properties of Wheat Bran. AB - Besides providing dietary fiber, wheat bran is a recognized source of protein and is considered a very valuable substitute for other protein-rich sources in the food and feed industry. Nonetheless, several factors affect protein bioavailability, including bran's layered structure. This study showed the influence on the release and protein modification of wheat bran of different bioprocessing methods involving the activation of endogenous enzymes of bran, the addition of an enzyme mixture having carbohydrase activity, and microbial fermentation. Bioprocessing in acidic conditions significantly enhanced the solubilization of protein from wheat bran, reaching the highest value in the treatment where the sole endogenous protease activity was activated. Bioprocessing through controlled fermentation allowed a more intense proteolysis and strongly impacted the in vitro digestibility of proteins. The combined use of starter cultures and cell-wall-degrading enzymes was characterized by the highest increase of phytase activity and total phenols. PMID- 26365886 TI - The politics of non-communicable diseases in the global South. AB - In this paper, we explore the emergence of non-communicable diseases (NCDs) as an object of political concern in and for countries of the global South. While epidemiologists and public health practitioners and scholars have long expressed concern with the changing global distribution of the burden of NCDs, it is only in more recent years that the aetiology, politics and consequences of these shifts have become an object of critical social scientific enquiry. These shifts mark the starting point for this special issue on 'The Politics of NCDs in the Global South' and act as the basis for new, critical interventions in how we understand NCDs. In this paper, we aim not only to introduce and contextualise the six contributions that form this special issue, but also to identify and explore three themes - problematisation, care and culture - that index the main areas of analytical and empirical concern that have motivated analyses of NCDs in the global South and are central to critical engagement with their political contours. PMID- 26365887 TI - Effect of early caffeine on neurodevelopmental outcome of very low-birth weight newborns. AB - OBJECTIVES: The objective of this study is to evaluate the effect of early caffeine therapy started within the first 48 h of life on neurodevelopmental outcome in very low birth weight (VLBW) newborns. STUDY DESIGN: VLBW newborns received either caffeine therapy within first 48 h of life (Early group), after 3rd day of life (Late group) or no caffeine during first month of life as per clinical team. A cohort of these newborns (n = 160) who survived were evaluated using Bayley Scale of Infant Development III (BSID III) developmental testing between 18 and 22 months of corrected age. RESULTS: VLBW newborns in the "Early group" had significantly better composite, cognitive, language and motor BSID III scores as compared to those in "Late group" and no caffeine group. Composite BSID III scores were unchanged in the presence or absence of chorioamnionitis for "Early group", while the BSID III scores were significantly lower in the presence of acute chorioamnionitis in "Late group" and no caffeine group. CONCLUSIONS: Early caffeine therapy was associated with better BSID III scores in a cohort of VLBW newborns. Newborns with acute chorioamnionitis benefited from early caffeine therapy. PMID- 26365888 TI - Alteration in Nuclear Factor-KappaB Pathway and Functionality of Estrogen via Receptors Promote Neuroinflammation in Frontal Cortex after 1-Methyl-4-Phenyl 1,2,3,6-Tetrahydropyridine Treatment. AB - The MPTP mediated neurodegeneration in substantia nigra has been well studied, but not the status of frontal cortex. The novelty of the present study is to explore the sex difference of frontal cortex during MPTP intoxication and to investigate the role of estrogen and its receptors in presence of glial cells in a time chase experiment; to identify which pathway of NF-kappaB exist to proceed the neuroinflammation; to investigate the estrogen binding with its nuclear or cytosolic receptors and whether any direct relation exists between estrogen receptor (ER) -beta and NF-kappaB molecules p65 and RelB. The progression of neurodegeneration occurred with the association of glial cells and functional (via its nuclear and cytosolic receptors) estrogen level. Both the canonical and/or non canonical pathways of NF-kappaB exist in frontal cortex of both the sexes after MPTP treatment. The homodimeric or heterodimeric form of ER-beta binds with NF-kappaB molecules p65 and RelB differently, but the canonical or non canonical pathways of NF-kappaB molecules could not be stopped or may be promoted. The changes in the molecular and cellular pattern in frontal cortex of both sexes during MPTP intoxication depends on the estrogen function via its nuclear or cytosolic estrogen receptors. PMID- 26365889 TI - Effect of Different Z-Inducers on the Stabilization of Z Portion in BZ-DNA Sequence: Correlation Between Experimental and Simulation Data. AB - In this study we show the outstanding agreement between simulation and experimental data concerning the efficient stabilization effect by NaCl of Z conformation. We demonstrate by circular dichroism (CD) experiments that Na(+) not only is able to induce a B to Z form transition in a short (GC)3 alternated portion of a sequence having 17 basis, but also is the best stabilizer in comparison with other Z inducers used (spermine and NiCl2). This result was confirmed by free energy calculations. PMID- 26365890 TI - An integrated energy plan for activated neurons. AB - This Editorial highlights an ingenious study by Li and Freeman published in this issue of J. Neurochem. Accurately knowing the brain extracellular levels of the two main substrates, that is, glucose and lactate, while a well-controlled and graded-stimulus is applied, might be extremely useful to finely understand how these substrates are produced and used. To that end, the authors have designed a new approach that consists to record at the same time (100 ms resolution) extracellular glucose and lactate concentrations using electrochemical sensing microelectrodes equally distant from a microelectrode that registers the multicellular activity in response to light-dependent stimuli (contrast levels from 10% to 80%). While this approach does, however, not evaluate the metabolic coupling between astrocytes and neurons, it proposes a new design which combined with molecular strategies specifically toward the glial or neuronal compartments will certainly help to demonstrate new distinctive features of this interesting question. PMID- 26365891 TI - Electrochemical detection of type 2 diabetes mellitus-related SNP via DNA mediated growth of silver nanoparticles on single walled carbon nanotubes. AB - Herein, we proposed a new electrochemical sensing strategy for T2DM-related SNP detection via DNA-mediated growth of AgNPs on a SWCNT-modified electrode. Coupled with RNase HII enzyme assisted amplification, this approach could realize T2DM related SNP assay and be applied in crude extracts of carcinoma pancreatic beta cell lines. PMID- 26365892 TI - Apoptosis and necrosis mediate skeletal muscle fiber loss in age-induced mitochondrial enzymatic abnormalities. AB - Sarcopenia, the age-induced loss of skeletal muscle mass and function, results from the contributions of both fiber atrophy and loss of myofibers. We have previously characterized sarcopenia in FBN rats, documenting age-dependent declines in muscle mass and fiber number along with increased fiber atrophy and fibrosis in vastus lateralis and rectus femoris muscles. Concomitant with these sarcopenic changes is an increased abundance of mitochondrial DNA deletion mutations and electron transport chain (ETC) abnormalities. In this study, we used immunohistological and histochemical approaches to define cell death pathways involved in sarcopenia. Activation of muscle cell death pathways was age dependent with most apoptotic and necrotic muscle fibers exhibiting ETC abnormalities. Although activation of apoptosis was a prominent feature of electron transport abnormal muscle fibers, necrosis was predominant in atrophic and broken ETC-abnormal fibers. These data suggest that mitochondrial dysfunction is a major contributor to the activation of cell death processes in aged muscle fibers. The link between ETC abnormalities, apoptosis, fiber atrophy, and necrosis supports the hypothesis that mitochondrial DNA deletion mutations are causal in myofiber loss. These studies suggest a progression of events beginning with the generation and accumulation of a mtDNA deletion mutation, the concomitant development of ETC abnormalities, a subsequent triggering of apoptotic and, ultimately, necrotic events resulting in muscle fiber atrophy, breakage, and fiber loss. PMID- 26365893 TI - Tissue Doppler Imaging predicts central sleep apnea in patients with chronic heart failure: data from the Daunia Registry. AB - BACKGROUND: Tissue Doppler imaging (TDI) is used to improve risk stratification in patients with chronic heart failure (CHF). So far, few studies have used this method to investigate the characteristics of subjects with CHF and Cheyne-Stokes breathing (CSB). The aim of this study was therefore to evaluate whether TDI assessment may predict the presence of CSB in patients with CHF. MATERIALS AND METHODS: A total of 41 consecutive patients with CHF enrolled in the Daunia Heart Failure Registry underwent echocardiography assessment and nocturnal polygraphy to evaluate the presence of sleep apnea and CSB. Conventional echocardiography and TDI parameters were calculated. We have also quantified by TDI a combined index (EAS index) of diastolic and systolic performance: E'/(A' * S'). RESULTS: Subjects with evidence of CSB (N = 8) were characterized by lower values of A' (5.03 +/- 2.64 vs. 7.88 +/- 2.64 cm/s, P < 0.01). A' and EAS index values were related to Cheyne-Stokes episode rates (r = -0.49 and 0.52, P < 0.05 and <0.01 respectively), EAS index values also with the number of episodes of central apnea (r = 0.39, P < 0.05). A' values predicted the presence of CSB at poly-somnography examination with an OR 0.62 (95% CI 0.40-0.96, P < 0.05) even after correction for age and gender. CONCLUSIONS: Tissue Doppler imaging values (A') are associated with the presence of sleep apnea at nocturnal polygraphy. PMID- 26365894 TI - Evaluation of body growth in prepubertal Japanese children with obstructive sleep apnea after adenotonsillectomy over a long postoperative period. AB - OBJECTIVE: The aim of this study was to identify changes in body growth patterns in prepubertal Japanese children with obstructive sleep apnea (OSA) after adenotonsillectomy (AT) over a long postoperative period. METHODS: We retrospectively analyzed the hospital records of 69 children, aged 3-10 years with OSA, who were followed-up for a median period of 38 months (range, 24-92 months) after AT. Height and weight were measured during the preoperative period and 12, and 24 months postoperatively, data were converted to standard deviation scores (SDS) using current gender- and age-specific values for the growth parameters adopted by the National growth chart of Japan. Comparisons between the pre and postoperative SDS values for height and weight were performed. The numerical data were examined statistically. RESULTS: The SDS for height and weight of Japanese OSA children significantly increased 24 months post AT and continued over the entire 24-month follow-up period. Height growth acceleration after AT ended earlier in children of 6.0 +/- 1.5 years at the time of AT than in children of 4.7 +/- 1.3 years who could not catch-up. CONCLUSION: In prepubertal Japanese children with OSA, AT was effective for the growth of those children over a long postoperative period. PMID- 26365895 TI - Injection laryngoplasty in children with cystic fibrosis and abnormal swallow. AB - OBJECTIVE: Children with cystic fibrosis (CF) are uniquely vulnerable to the pulmonary complications of chronic aspiration. We present a case series of children with CF and evidence of chronic aspiration who underwent injection laryngoplasty to improve the safety and efficacy of their swallow. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary care children's hospital. METHODS/SUBJECTS: A chart review was performed on three consecutive cases of children with CF and evidence of aspiration on modified barium swallow (MBS) evaluated at a tertiary care, academic children's medical center. RESULTS: Three patients with CF underwent injection laryngoplasty for evidence of aspiration or laryngeal penetration on MBS evaluation. Normal laryngeal anatomy was identified intraoperatively in each case. At the time of the procedure, patients were 22 months, 70 months, and 24 months old, and follow-up information was available for 7 months, 11 months, and 12 months post-procedure, respectively. Presenting symptoms included chronic cough, cough with oral liquids, and recurrent pneumonia. Each patient underwent successful injection into the interarytenoid space. Post-operatively, modified barium swallow demonstrated resolution of aspiration or penetration in all patients. No procedure-related complications were encountered. CONCLUSION: Patients with CF are highly susceptible to pulmonary infections, and aggressive treatment of chronic aspiration is often necessary. Injection laryngoplasty may be effective in normalizing swallowing in these children. Future study will elucidate the duration of effect and if this technique improves long-term pulmonary outcomes in CF patients. PMID- 26365896 TI - Resistance to BRAF inhibitors induces glutamine dependency in melanoma cells. AB - BRAF inhibitors can extend progression-free and overall survival in melanoma patients whose tumors harbor mutations in BRAF. However, the majority of patients eventually develop resistance to these drugs. Here we show that BRAF mutant melanoma cells that have developed acquired resistance to BRAF inhibitors display increased oxidative metabolism and increased dependency on mitochondria for survival. Intriguingly, the increased oxidative metabolism is associated with a switch from glucose to glutamine metabolism and an increased dependence on glutamine over glucose for proliferation. We show that the resistant cells are more sensitive to mitochondrial poisons and to inhibitors of glutaminolysis, suggesting that targeting specific metabolic pathways may offer exciting therapeutic opportunities to treat resistant tumors, or to delay emergence of resistance in the first-line setting. PMID- 26365897 TI - Associations between a patient-reported outcome (PRO) measure of sarcopenia and falls, functional status, and physical performance in older patients with cancer. AB - OBJECTIVE: In older patients with cancer, we aimed to investigate associations between a patient-reported outcome measure for sarcopenia (SarcoPRO) and the Short Physical Performance Battery (SPPB), self-reported falls, and limitations in instrumental activities of daily living (IADLs). MATERIALS AND METHODS: Assessments were conducted as part of the initial evaluation of older, often frail, patients with cancer seen in the Specialized Oncology Care and Research in the Elderly (SOCARE) clinic. Univariate associations were evaluated using Spearman's correlation and Wilcoxon sign ranked tests. Logistic regressions were used to identify associations of clinical factors and SarcoPRO scores or SPPB scores with falls and IADL limitations. RESULTS: In total, 174 older patients with cancer were evaluated. A moderate correlation was found between the SarcoPRO and the SPPB (rho=0.62). After adjusting for multiple clinical factors, neither the SarcoPRO nor the SPPB were associated with falls. In contrast, both higher SarcoPRO (i.e., worse) and lower SPPB (i.e., worse) scores were associated with limitations in IADLs (odds ratio for one unit change in predictor: SarcoPRO: 1.06, p<0.0001; SPPB: 0.71, p=0.003, respectively). Models using the SarcoPRO and SPPB explained similar amounts of variability in association with IADL limitations (AUC: 0.88 vs. 0.87, respectively). CONCLUSIONS: The SarcoPRO was moderately associated with the SPPB, an objective measure of physical performance, and was associated with limitations in IADLs. Thus, older patients with cancer who present with IADL limitations should be screened for sarcopenia. The SarcoPRO shows promise as a measure for screening as well as outcome assessment for research on sarcopenia. PMID- 26365898 TI - Prevalence of sarcopenia in older patients with colorectal cancer. AB - OBJECTIVE: Sarcopenia is the age-related loss of muscle mass, strength, and function. It is a common finding in older patients and is associated with decreased life expectancy and potentially higher susceptibility to chemotherapy toxicity. This study describes the prevalence of sarcopenia in older adults with early stage colorectal cancer. MATERIALS AND METHODS: Patients >=70 years old who underwent surgical resection for stage I-III colorectal cancer between 2008 and 2013 were identified from the medical record. Sarcopenia was assessed by measuring the total muscle area on computerized tomography (CT) images obtained prior to surgery. Total muscle area was measured at the level of L3 and normalized using each patient's height to produce a skeletal muscle index (SMI). Sarcopenia was defined using sex- and body mass index (BMI)-specific threshold values of SMI. RESULTS: Eighty-seven patients were included, with a median age of 77 years (70-96). Twenty-five men (60% of 42) and 25 women (56% of 45) had sarcopenia. Sarcopenic patients had significantly lower BMI (p=0.03) compared to non-sarcopenic patients. There was a positive correlation between BMI and SMI for both men (r=0.44) and women (r=0.16). CONCLUSION: Sarcopenia is highly prevalent among older patients with early stage colorectal cancer. BMI alone is a poor indicator of lean body mass and improved methods of screening for sarcopenia are necessary. CT scans are a viable option for identifying sarcopenic patients in whom timely interventions may improve survival, quality of life, and functional outcomes. PMID- 26365899 TI - Current Pretreatment Technologies for the Development of Cellulosic Ethanol and Biorefineries. AB - Lignocellulosic materials, such as forest, agriculture, and agroindustrial residues, are among the most important resources for biorefineries to provide fuels, chemicals, and materials in such a way to substitute for, at least in part, the role of petrochemistry in modern society. Most of these sustainable biorefinery products can be produced from plant polysaccharides (glucans, hemicelluloses, starch, and pectic materials) and lignin. In this scenario, cellulosic ethanol has been considered for decades as one of the most promising alternatives to mitigate fossil fuel dependence and carbon dioxide accumulation in the atmosphere. However, a pretreatment method is required to overcome the physical and chemical barriers that exist in the lignin-carbohydrate composite and to render most, if not all, of the plant cell wall components easily available for conversion into valuable products, including the fuel ethanol. Hence, pretreatment is a key step for an economically viable biorefinery. Successful pretreatment method must lead to partial or total separation of the lignocellulosic components, increasing the accessibility of holocellulose to enzymatic hydrolysis with the least inhibitory compounds being released for subsequent steps of enzymatic hydrolysis and fermentation. Each pretreatment technology has a different specificity against both carbohydrates and lignin and may or may not be efficient for different types of biomasses. Furthermore, it is also desirable to develop pretreatment methods with chemicals that are greener and effluent streams that have a lower impact on the environment. This paper provides an overview of the most important pretreatment methods available, including those that are based on the use of green solvents (supercritical fluids and ionic liquids). PMID- 26365901 TI - An economic model to assess the cost-benefit of BNCT. AB - We have constructed a formal model on cost-benefit of new technology in health care, and apply it on boron neutron capture therapy (BNCT). We assume that the patient health benefit from getting cured in acute treatment is always higher than the patient utility resulting from any long term treatment or death. This assumption makes it possible to evaluate the monetary cost impacts of a new technology and relate these measures to the patient health benefit. PMID- 26365900 TI - GATA2 regulates Wnt signaling to promote primitive red blood cell fate. AB - Primitive erythropoiesis is regulated in a non cell-autonomous fashion across evolution from frogs to mammals. In Xenopus laevis, signals from the overlying ectoderm are required to induce the mesoderm to adopt an erythroid fate. Previous studies in our lab identified the transcription factor GATA2 as a key regulator of this ectodermal signal. To identify GATA2 target genes in the ectoderm required for red blood cell formation in the mesoderm, we used microarray analysis to compare gene expression in ectoderm from GATA2 depleted and wild type embryos. Our analysis identified components of the non-canonical and canonical Wnt pathways as being reciprocally up- and down-regulated downstream of GATA2 in both mesoderm and ectoderm. We show that up-regulation of canonical Wnt signaling during gastrulation blocks commitment to a hematopoietic fate while down regulation of non-canonical Wnt signaling impairs erythroid differentiation. Our results are consistent with a model in which GATA2 contributes to inhibition of canonical Wnt signaling, thereby permitting progenitors to exit the cell cycle and commit to a hematopoietic fate. Subsequently, activation of non-canonical Wnt signaling plays a later role in enabling these progenitors to differentiate as mature red blood cells. PMID- 26365902 TI - A quinary layer transition metal oxide of NaNi1/4Co1/4Fe1/4Mn1/8Ti1/8O2 as a high rate-capability and long-cycle-life cathode material for rechargeable sodium ion batteries. AB - A well-crystallized single-phase quinary layer transition metal oxide of NaNi1/4Co1/4Fe1/4Mn1/8Ti1/8O2 was successfully synthesized. It exhibited excellent cycle performance and high rate capability as a cathode material for sodium-ion batteries. PMID- 26365903 TI - Better prediction by use of co-data: adaptive group-regularized ridge regression. AB - For many high-dimensional studies, additional information on the variables, like (genomic) annotation or external p-values, is available. In the context of binary and continuous prediction, we develop a method for adaptive group-regularized (logistic) ridge regression, which makes structural use of such 'co-data'. Here, 'groups' refer to a partition of the variables according to the co-data. We derive empirical Bayes estimates of group-specific penalties, which possess several nice properties: (i) They are analytical. (ii) They adapt to the informativeness of the co-data for the data at hand. (iii) Only one global penalty parameter requires tuning by cross-validation. In addition, the method allows use of multiple types of co-data at little extra computational effort. We show that the group-specific penalties may lead to a larger distinction between 'near-zero' and relatively large regression parameters, which facilitates post hoc variable selection. The method, termed GRridge, is implemented in an easy-to use R-package. It is demonstrated on two cancer genomics studies, which both concern the discrimination of precancerous cervical lesions from normal cervix tissues using methylation microarray data. For both examples, GRridge clearly improves the predictive performances of ordinary logistic ridge regression and the group lasso. In addition, we show that for the second study, the relatively good predictive performance is maintained when selecting only 42 variables. PMID- 26365904 TI - Development of real-time PCR assays for the detection of Moraxella macacae associated with bloody nose syndrome in rhesus (Macaca mulatta) and cynomolgus (Macaca fascicularis) macaques. AB - BACKGROUND: Moraxella macacae is a recently described bacterial pathogen that causes epistaxis or so-called bloody nose syndrome in captive macaques. The aim of this study was to develop specific molecular diagnostic assays for M. macacae and to determine their performance characteristics. METHODS: We developed six real-time PCR assays on the Roche LightCycler. The accuracy, precision, selectivity, and limit of detection (LOD) were determined for each assay, in addition to further validation by testing nasal swabs from macaques presenting with epistaxis at the Tulane National Primate Research Center. RESULTS: All assays exhibited 100% specificity and were highly sensitive with an LOD of 10 fg for chromosomal assays and 1 fg for the plasmid assay. Testing of nasal swabs from 10 symptomatic macaques confirmed the presence of M. macacae in these animals. CONCLUSIONS: We developed several accurate, sensitive, and species specific real-time PCR assays for the detection of M. macacae in captive macaques. PMID- 26365905 TI - Efficacy and safety of sodium-glucose cotransporter 2 inhibitors in type 2 diabetes: a meta-analysis of randomized controlled trials for 1 to 2years. AB - AIMS: To evaluate the mid long-term efficacy and safety of sodium-glucose cotransporter 2 (SGLT2) inhibitors in adults with type 2 diabetes mellitus (T2DM). METHODS: Three databases including Pubmed, Embase, and Cochrane Library were searched for randomized controlled trials (RCTs) of SGLT2 inhibitors that lasted for at least 52weeks. Two reviewers retrieved the literature and evaluated study quality using the Modified Jadad Score Scale. The outcome measures were pooled using random or fixed effects models. RESULTS: Fourteen articles of 13 RCTs were included in this meta-analysis. Compared to a placebo, the SGLT2 inhibitors significantly reduced glycated hemoglobin (HbA1c) [for 1year result, weighted mean differences (WMDs): -0.491%; 95% confidence intervals (CIs): -0.573 to -0.410; I(2)=39.9%, for 2years result, WMD: -0.503%; 95% CI: -0.742 to -0.265; I(2)=70.7%], fasting plasma glucose (FPG) (for 1year result, WMD: -0.809; 95% CI: -0.858 to -0.761; I(2)=56.4%; for 2years result, WMD: -0.764; 95% CI: -1.026 to 0.501; I(2)=39.4%), body weight (BW) (for 1year result, WMD: -2.477; 95% CI: 2.568 to -2.385; I(2)=0.0%; for 2years result, WMD: -2.990; 95% CI: -3.642 to 2.337; I(2)=0.0%), systolic blood pressure (SBP) (for 1year result, WMD: -2.874; 95% CI: -4.528 to -1.220; I(2)=98.1%; for 2years result, WMD: -7.500; 95% CI: 7.698 to -7.302) and diastolic blood pressure (DBP) (for 1year result, WMD: 1.950; 95% CI: -2.890 to -1.010; I(2)=98.0%; for 2years result, WMD: -2.197; 95% CI: -3.112 to -1.283). Compared to oral antidiabetic drugs (OADs), the SGLT2 inhibitors also reduced HbA1c, FPG, BW, SBP and DBP significantly. Compared to a placebo, the SGLT2 inhibitors increase the risk of hypoglycemia [odds ratios (ORs): 1.214; 95% CI: 1.036 to 1.423; I(2)=47.7%], urinary infection (OR: 1.477; 95% CI: 1.172 to 1.861; I(2)=46.6%) and genital tract infections (OR: 4.196; 95% CI: 2.332 to 7.549; I(2)=52.7%). Compared to OADs, SGLT2 inhibitors showed a remarkable reduction of hypoglycemia incidence (OR: 0.202; 95% CI: 0.059 to 0.691; I(2)=97.8%), but increased the incidence of genital tract infections (OR: 5.715; 95% CI: 4.339 to 7.528; I(2)=0.0%) and urinary infection (OR: 1.192; 95% CI: 0.990 to 1.434; I(2)=45.3%). SGLT2 inhibitors did not decrease estimated glomerular filtration rate (eGFR) when comparing with placebos [(for absolute value change, WMD: 0.629mL/min/1.73m(2); 95% CI: -1.250 to 2.508; I(2)=0.0%); (for percent change, WMD: -2.274%; 95% CI: -5.410 to 0.861; I(2)=54.5%)] and OADs (for percent change, WMD: 0.356%; 95% CI: -0.967 to 1.679; I(2)=0.0%). CONCLUSION: SGLT2 inhibitors have favorable effects on combating hyperglycemia for mid long-term; likewise, they have additional benefits beyond glycemic control such as reducing body weight and lowering blood pressure. PMID- 26365906 TI - Severe lethal phenotype of a Japanese case of Netherton syndrome with homozygous founder mutations of SPINK5 c.375_376delAT. PMID- 26365907 TI - A pilot study of JI-101, an inhibitor of VEGFR-2, PDGFR-beta, and EphB4 receptors, in combination with everolimus and as a single agent in an ovarian cancer expansion cohort. AB - JI-101 is an oral multi-kinase inhibitor that targets vascular endothelial growth factor receptor type 2 (VEGFR-2), platelet derived growth factor receptor beta (PDGFR-beta), and ephrin type-B receptor 4 (EphB4). None of the currently approved angiogenesis inhibitors have been reported to inhibit EphB4, and therefore, JI-101 has a novel mechanism of action. We conducted a pilot trial to assess the pharmacokinetics (PK), tolerability, and efficacy of JI-101 in combination with everolimus in advanced cancers, and pharmacodynamics (PD), tolerability, and efficacy of JI-101 in ovarian cancer. This was the first clinical study assessing anti-tumor activity of JI-101 in a combinatorial regimen. In the PK cohort, four patients received single agent 10 mg everolimus on day 1, 10 mg everolimus and 200 mg JI-101 combination on day 8, and single agent 200 mg JI-101 on day 15. In the PD cohort, eleven patients received single agent JI-101 at 200 mg twice daily for 28 day treatment cycles. JI-101 was well tolerated as a single agent and in combination with everolimus. No serious adverse events were observed. Common adverse events were hypertension, nausea, and abdominal pain. JI-101 increased exposure of everolimus by approximately 22%, suggestive of drug-drug interaction. The majority of patients had stable disease at their first set of restaging scans (two months), although no patients demonstrated a response to the drug per RECIST criteria. The novel mechanism of action of JI-101 is promising in ovarian cancer treatment and further prospective studies of this agent may be pursued in a less refractory patient population or in combination with cytotoxic chemotherapy. PMID- 26365908 TI - One-pot preparation of a mixed-mode organic-silica hybrid monolithic capillary column and its application in determination of endogenous gibberellins in plant tissues. AB - A newly improved one-pot method, based on "thiol-ene" click chemistry and sol-gel approach in microemulsion system, was developed for the preparation of C8/PO(OH)2 silica hybrid monolithic capillary column. The prepared monolith possesses large specific surface area, narrow mesopore size distribution and high column efficiency. The monolithic column was demonstrated to have cation exchange/reversed-phase (CX/RP) mixed-mode retention for analytes on nano-liquid chromatography (nano-LC). On the basis of the developed nano-LC system with MS detector coupled to pipette tip solid phase extraction (PT-SPE) and derivatization process, we then realized simultaneous determination of 10 gibberellins (GAs) with low limits of detection (LODs, 0.003-0.025 ng/mL). Furthermore, 6 endogenous GAs in only 5mg rice leaves (fresh weight) were successfully detected and quantified. The developed PT-SPE-nano-LC-MS strategy may offer promising applications in the determination of low abundant bioactive molecules from complex matrix. PMID- 26365909 TI - Simultaneous determination of hydrophobicity and dissociation constant for a large set of compounds by gradient reverse phase high performance liquid chromatography-mass spectrometry technique. AB - Fast and reliable methods for the determination of hydrophobicity and acidity are desired in pre-clinical drug development phases to eliminate compounds with poor pharmacokinetic properties. Reversed-phase high-performance liquid chromatography (RP HPLC) coupled with time-of-flight mass spectrometry (RP HPLC-ESI-TOF-MS) is a convenient technique for that purpose. In this work we determined the chromatographic measure of hydrophobicity (logkw) and dissociation constant (pKa) simultaneously for a large and diverse group of 161 drugs. Retention times were determined by means of RP HPLC-ESI-TOF-MS for a series of pH and organic modifier gradients. We were able to measure retention times for 140 out of 161 (87%) compounds. For those analytes logkw and pKa parameters were calculated and compared with literature and ACD Labs-calculated data. The determined chromatographic measure of hydrophobicity and dissociation constant was closely related to literature and theoretically calculated values. Applied methodology achieved the medium-throughput screening rate of 100 compounds per day and proved to be a simple, fast and reliable approach of assessing important physicochemical properties of drugs. This technique has certain limitations as it is not applicable for very hydrophilic analytes (logP<0.5) and compounds with identical molar masses. PMID- 26365910 TI - A facile and versatile approach for controlling electroosmotic flow in capillary electrophoresis via mussel inspired polydopamine/polyethyleneimine co-deposition. AB - Electroosmotic flow (EOF), which reveals the charge property of capillary inner surface, has an important impact on the separation performance and reproducibility of capillary electrophoresis (CE). In this study, a novel, facile and versatile method to achieve diverse and controllable EOF in CE was reported based on the co-deposition of mussel-inspired polydopamine (PDA) and branched polyethyleneimine (PEI) on the capillary inner surface as the hybrid functional coating. After these PDA/PEI co-deposited columns were reinforced by the post incubation of FeCl3, various magnitude and direction of EOF in CE could be easily achieved by varying a number of preparation parameters, including the mass ratio of DA/PEI and the molecular weight of PEI (including PEI-600, PEI-1800, PEI-10000 and PEI-70000). The separation effectiveness and stability of the hybrid coated columns were verified by the analysis of aromatic acids and aniline derivatives. The results showed that the controllable and diverse EOF was important in enhancing the separation performance of the analytes. The baseline separation of all the five aromatic acids can be achieved in 7 min with high separation efficiency by using the PDA/PEI-600 co-deposited column with the mass ratio of 6:1. On the other hand, with the PDA/PEI-70000 co-deposited column with the mass ratio of 6:1, the aniline compounds were easily baseline separated within 10 min. By contrast, using the bare and PDA coated columns, the migration of the aromatic acids was very slow and the baseline separation of the aniline compounds cannot be obtained. Moreover, the co-deposited columns showed long lifetime and good stability. The relative standard deviations for intra-day, inter-day and capillary-to-capillary repeatability of the PDA/PEI-600 co-deposited column with the mass ratio of 6:1, which was reinforced by the post-incubation of FeCl3, were all lower than 5%. PMID- 26365911 TI - High performance liquid chromatographic enantioseparation development and analytical method characterization of the carboxylate ester of evacetrapib using an immobilized chiral stationary phase with a non-conventional eluent system. AB - Using multiple HPLC chromatographic modes and various chiral columns in the context of an automated screening system, a potential separation was initially identified for the methyl ester of evacetrapib and its stereoisomers using an immobilized polysaccharide-based HPLC column. The bonded nature of this column, the Chiralpak((r)) IC, allows for enhanced separation development with a diverse solvent range not amenable to standard coated chiral stationary phases. The ternary eluent system ultimately identified provided isomer resolutions not obtainable via the more established hexane/alcohol or polar organic chromatographic modes. A systematic separation development process is described, first for the resolution of the isomers, and later incorporating five potential impurities. A robust separation system was eventually developed that effectively resolves all compounds within a reasonable analysis time. PMID- 26365912 TI - Automated hollow-fiber liquid-phase microextraction coupled with liquid chromatography/tandem mass spectrometry for the analysis of aflatoxin M1 in milk. AB - An automated hollow fiber liquid-phase microextraction (HF-LPME) coupled with liquid chromatography/tandem mass spectrometry (LC-MS/MS) method was developed for the extraction and determination of aflatoxin M1 (AFM1) in milk samples. Parameters affecting the extraction efficiency, such as the extraction phase, matrix conditions, extraction time and temperature, were investigated. Under the optimal conditions (ratio of water to milk, 4:1; extraction time, 50 min; extraction temperature, 50 degrees C; extraction phase, 50 mg L(-1) anti-AFM1 antibody in PBS buffer solution; volume of HCl solution, 250 MUL; agitation speed, 250 rpm), the matrix-matched calibration curve for AFM1 determination showed good linearity in the range of 0.25-5 MUg kg(-1). The enrichment factor (EF) reached 48, and the limits of detection and quantification were 0.06 and 0.21 MUg kg(-1), respectively. The developed method was successfully applied for the extraction of AFM1 from spiked milk samples, with recoveries from 61.0% to 106.7%. The method was highly specific to AFM1 analysis, and the results demonstrated that the method can be automated, inexpensive, and free from interference. PMID- 26365914 TI - Vinylogous Nicholas reactions in the synthesis of bi- and tricyclic cycloheptynedicobalt complexes. AB - The Lewis acid mediated intramolecular Nicholas reactions of allylic acetate enyne-Co2(CO)6 complexes afford cycloheptenyne-Co2(CO)6 complexes in three manifestations. Electron rich aryl substituted alkyne complexes give tricyclic 6,7,x-benzocycloheptenyne complexes, with x = 5, 6, or 7. Allylsilane substituted complexes afford exo methylene bicyclic x,7-cycloheptenyne complexes (x = 6,7). The allyl acetate function may also be replaced by a benzylic acetate, to afford dibenzocycloheptyne-Co2(CO)6 complexes. Following reductive complexation, the methodology may be applied to the synthesis of the icetexane diterpene carbon framework. PMID- 26365913 TI - Impact of extraction and elution media on non-size effects in size exclusion chromatography of proteins. AB - Size exclusion chromatography is extensively used to separate proteins and to determine their apparent molecular weights. It separates proteins based on hydrodynamic volume, but interactions between the chromatography resin and proteins lead to non-size effects. This report discusses the impact of co solvents [salt, urea, sodium dodecyl sulfate (SDS), dithiothreitol] in extraction media when separating wheat gluten proteins, soy glycinin, bovine serum albumin and ovalbumin on a Biosep-SEC-S4000 column. With acetonitrile/water (1:1, v/v) containing 0.05% (v/v) trifluoroacetic acid as eluent, salts and SDS in the extraction media increase while urea decreases non-size effects. Most gluten and globular proteins are extractable in sodium phosphate buffer (0.050M; pH 6.8) containing 2.0% (w/v) SDS. This chromatographic medium allows analyzing mixtures of various proteins without any non-size effects. PMID- 26365915 TI - Proteomic analysis through larval development of Solea senegalensis flatfish. AB - The post-embryonic development of the Senegalese sole, Solea senegalensis, a flatfish of growing interest in fisheries and aquaculture, is associated with drastic morpho-physiological changes during metamorphosis. Although in the last two decades knowledge on sole culture has notably increased, especially in Southern Europe, its progress was restricted due to lack of methods to control reproduction, improve larval quality and increase juvenile disease resistance. A limited knowledge of the physiological, molecular and genetic mechanisms involved is at the base of such limitation. A proteomic study was carried out to explore the molecular events that occur during S. senegalensis ontogenesis. Protein expression changes were monitored in larvae from 5 to 21 dph by combining 2DE and protein identification with de novo MS/MS sequencing. An average of 6177 +/- 282 spots was resolved in 2DE gels. Hierarchical cluster analysis of the 705 selected spots grouped them in eight patterns. Thirty-four proteins were identified and assigned biological functions including structure, metabolism highlighting energy metabolism, transport, protein folding, stress response, chromatin organization and regulation of gene expression. These changes provide a sequential description of the molecular events associated with the biochemical and biological transformations that occur during sole larval development. PMID- 26365916 TI - Partial in vitro analysis of toxic and antigenic activities of eleven Peruvian pitviper snake venoms. AB - This work used eleven Peruvian snake venoms (Bothrops andianus, Bothrops atrox, Bothrops barnetti, Bothrops castelnaudi, Bothriopsis chloromelas, Bothrocophias microphthalmus, Bothrops neuwiedi, Bothriopsis oligolepis, Bothriopsis peruviana, Bothrops pictus and Bothriopsis taeniata) to perform in vitro experimentation and determine its main characteristics. Hyaluronidase (HYAL), phospholipase A2 (PLA2), snake venom metalloproteinase (SVMP), snake venom serine protease (SVSP) and L-amino acid oxidase (LAAO) activities; toxicity by cell viability assays using MGSO3, VERO and HeLa cell lineages; and crossed immunoreactivity with Peruvian (PAV) and Brazilian (BAV) antibothropic polyvalent antivenoms, through ELISA and Western Blotting assays, were determined. Results show that the activities tested in this study were not similar amongst the venoms and each species present their own peculiarities, highlighting the diversity within Bothrops complex. All venoms were capable of reducing cell viability of all tested lineages. It was also demonstrated the crossed recognition of all tested venoms by both antivenoms. PMID- 26365917 TI - Botulinum neurotoxins for the treatment of focal dystonias: Review of rating tools used in clinical trials. AB - Botulinum neurotoxins (BoNTs) are used to achieve therapeutic benefit in focal dystonia. An expert panel recently reviewed published evidence on the efficacy of BoNTs for the treatment of focal dystonias and produced recommendations for clinical practice. Another panel reviewed the clinimetric properties of rating scales for dystonia and produced recommendations for current usage and future directions. Considering that the strength of evidence derives not only from the quality of the study design, but also from usage of validated outcome measures, we combined the information provided by these two recent reviews and assessed the appropriateness of the rating instruments used in clinical trials on BoNT treatment in focal dystonia. Data sources included all the publications on BoNT treatment for focal dystonias reviewed by the recent evidence-based analysis. We reviewed all rating instruments used to assess primary and secondary outcome following BoNT treatment. The publications were allocated into five topics according to the focal dystonia type reviewed in the meta-analysis: blepharospasm, oromandibular dystonia, cervical dystonia, upper limb dystonia, and laryngeal dystonia. For each topic, papers were divided, according to the terminology used in the meta-analysis, into placebo-controlled, active comparator and methodological or uncontrolled. For each topic we identified the rating tools used in each study class and annotated which were the mostly used in each focal dystonia type. Outcome measures included tools related to motor and non-motor features, such as pain and depression, and functional as well as health-related quality of life features. Patient- and investigator-reported outcomes were also included. Rating instruments were classified as recommended, suggested, listed or not included, based on recommendations produced by the rating scale task force. Both primary and secondary outcome measures were assessed. As a final step we compared current practice, as summarized by the meta-analysis, with the recommendations of the rating scales panel. For blepharospasm, three placebo controlled trials used suggested scales, one active-comparator study used a recommended scale and three active-comparator studies used suggested scales. For oromandibular dystonia, one placebo-controlled study used a suggested scale. For cervical dystonia, six placebo-controlled trials used a recommended scale, four active-comparator trials used a recommended scale and one active-comparator study used a suggested scale. For upper limb and laryngeal dystonia, no trial used validated instruments. Appropriately designed studies should be based on recommended rating instruments. Therapeutic trials not using clinimetrically tested rating measures do not provide sufficient information on efficacy of BoNT treatment, even if the study design is robust. Further research is needed to develop and validate new tools to assess all types of focal dystonia and to apply them in prospective placebo-controlled clinical trials. PMID- 26365918 TI - Dangerous reef aquaristics: Palytoxin of a brown encrusting anemone causes toxic corneal reactions. AB - Although frequently observed in domestic saltwater aquariums, literature on exposure to palytoxin (PTX) of encrusting anemones (Zoanthidea) kept in aquariums is rare. Handling these animals for propagation purposes or during cleaning work can lead to dermal, ocular or respiratory contact with the PTX generated by some Zoanthids. The present study describes a case of ocular exposure to liquid from a Zoanthid, which led to corneal ulcers. The patient also suffered from systemic symptoms of dyspnea and shivering and a suspected rhabdomyolysis, which required monitoring in the Intensive Care Unit. After symptomatic treatment provided insufficient results, the corneal ulcers improved with an amniotic membrane transplantation. A review of the literature regarding ocular exposures to this diverse order of Hexacorallia reveals that severe and systemic symptoms can develop with minimal contact. PMID- 26365919 TI - Botulinum toxin and the treatment of headache: A clinical review. AB - Since its discovery, Onabotulinum toxins have been tried for the treatment of various head, neck and face pain syndromes. The end result of controlled clinical trials was that there was not clear evidence for use in many of the common primary and secondary headaches. In chronic migraine, affecting 1-2% of the population, a fixed site and fixed dose treatment approach was shown to be superior to placebo and was approved for use. In this review, evidence for that use and the history leading to it is described. PMID- 26365920 TI - Theoretical vibrational spectra of OH(-)(H2O)2: the effect of quantum distribution and vibrational coupling. AB - We performed ab initio path integral molecular dynamics simulations for the hydroxide-water cluster, OH(-)(H2O)2, at 50 K, 100 K, and 150 K to investigate its flexible structure. From our simulations, we found that nuclear quantum effects enhance hydroxide hydrogen atom inversion and the conformational change between isomers occurs by simultaneous rotation of the free hydrogen atom. We propose the importance of including the transition state conformer with C2 symmetry, for the description of this system at temperatures realized in predissociation experiments. Temperature dependence of relative populations of each conformer along with multidimensional vibrational calculations were used to simulate the vibrational spectra and compare with the experimental spectra of Johnson and coworkers. We assign the doublet peaks seen in the experiment at 2500 to 3000 cm(-1), as the mixture of the ionic hydrogen bonded OH stretching overtone, ionic hydrogen bonded OH bending overtone, and the combination band of the ionic hydrogen bonded OH stretch and bend, which are modulated by the van der Waals OO vibrations. We concluded that for OH(-)(H2O)2, the vibrational couplings between the ionic hydrogen bonded motion and floppy modes contribute to the broadening of peaks observed in the 2500 to 3000 cm(-1) region. PMID- 26365921 TI - Time-Driven Activity-Based Costing in Emergency Medicine. AB - Value in emergency medicine is determined by both patient-important outcomes and the costs associated with achieving them. However, measuring true costs is challenging. Without an understanding of costs, emergency department (ED) leaders will be unable to determine which interventions might improve value for their patients. Although ongoing research may determine which outcomes are meaningful, an accurate costing system is also needed. This article reviews current costing mechanisms in the ED and their pitfalls. It then describes how time-driven activity-based costing may be superior to these current costing systems. Time driven activity-based costing, in addition to being a more accurate costing system, can be used for process improvements in the ED. PMID- 26365923 TI - Exaggerated displays do not improve mounting success in male seaweed flies Fucellia tergina (Diptera: Anthomyiidae). AB - Signals of individual quality are assumed to be difficult to exaggerate, either because they are directly linked to underlying traits (indices) or because they are costly to perform (handicaps). In practise advertisement displays may consist of conventional and costly components, for instance where a morphological structure related to body size is used in visual displays. In this case, there is the potential for dishonest displays, due to the population level variance around the relationship between body size and display structures. We examine the use of wing flicking displays that we observed in situ in a strandline dwelling seaweed fly Fucellia tergina, using overall body size and the size of their eyes as underlying indicators of condition. Males displayed far more frequently than females, and were also observed to frequently mount other flies, a behaviour that was rare in females. The rate of display was greater for males that had positive residual values from relationships between wing length and body length. In other words those males with larger than expected wings for their underlying quality displayed more frequently, indicating that these displays are open to exaggeration. Males with larger than expected wings (for the size of their body or eyes), however, mounted less frequently. We suggest that small bodied males are less successful in terms of mounting, but that those small males with relatively large wings may attempt to compensate for this through increased display effort. PMID- 26365922 TI - GPR120: A bi-potential mediator to modulate the osteogenic and adipogenic differentiation of BMMSCs. AB - Free fatty acids display diverse effects as signalling molecules through GPCRs in addition to their involvement in cellular metabolism. GPR120, a G protein-coupled receptor for long-chain unsaturated fatty acids, has been reported to mediate adipogenesis in lipid metabolism. However, whether GPR120 also mediates osteogenesis and regulates BMMSCs remain unclear. In this study, we showed that GPR120 targeted the bi-potential differentiation of BMMSCs in a ligand dose dependent manner. High concentrations of TUG-891 (a highly selective agonist of GPR120) promoted osteogenesis via the Ras-ERK1/2 cascade, while low concentrations elevated P38 and increased adipogenesis. The fine molecular regulation of GPR120 was implemented by up-regulating different integrin subunits (alpha1, alpha2 and beta1; alpha5 and beta3). The administration of high doses of TUG-891 rescued oestrogen-deficient bone loss in vivo, further supporting an essential role of GPR120 in bone metabolism. Our findings, for the first time, showed that GPR120-mediated cellular signalling determines the bi-potential differentiation of BMMSCs in a dose-dependent manner. Additionally, the induction of different integrin subunits was involved in the cytoplasmic regulation of a seesaw-like balance between ERK and p38 phosphorylation. These findings provide new hope for developing novel remedies to treat osteoporosis by adjusting the GPR120-mediated differentiation balance of BMMSCs. PMID- 26365924 TI - Fast and Accurate Data Extraction for Near Real-Time Registration of 3-D Ultrasound and Computed Tomography in Orthopedic Surgery. AB - Automatic, accurate and real-time registration is an important step in providing effective guidance and successful anatomic restoration in ultrasound (US)-based computer assisted orthopedic surgery. We propose a method in which local phase based bone surfaces, extracted from intra-operative US data, are registered to pre-operatively segmented computed tomography data. Extracted bone surfaces are downsampled and reinforced with high curvature features. A novel hierarchical simplification algorithm is used to further optimize the point clouds. The final point clouds are represented as Gaussian mixture models and iteratively matched by minimizing the dissimilarity between them using an L2 metric. For 44 clinical data sets from 25 pelvic fracture patients and 49 phantom data sets, we report mean surface registration accuracies of 0.31 and 0.77 mm, respectively, with an average registration time of 1.41 s. Our results suggest the viability and potential of the chosen method for real-time intra-operative registration in orthopedic surgery. PMID- 26365925 TI - Multidimensional Ultrasound Doppler Signal Analysis for Fetal Activity Monitoring. AB - Fetal activity parameters such as movements, heart rate and the related parameters are essential indicators of fetal wellbeing, and no device provides simultaneous access to and sufficient estimation of all of these parameters to evaluate fetal health. This work was aimed at collecting these parameters to automatically separate healthy from compromised fetuses. To achieve this goal, we first developed a multi-sensor-multi-gate Doppler system. Then we recorded multidimensional Doppler signals and estimated the fetal activity parameters via dedicated signal processing techniques. Finally, we combined these parameters into four sets of parameters (or four hyper-parameters) to determine the set of parameters that is able to separate healthy from other fetuses. To validate our system, a data set consisting of two groups of fetal signals (normal and compromised) was established and provided by physicians. From the estimated parameters, an instantaneous Manning-like score, referred to as the ultrasonic score, was calculated and was used together with movements, heart rate and the associated parameters in a classification process employing the support vector machine method. We investigated the influence of the sets of parameters and evaluated the performance of the support vector machine using the computation of sensibility, specificity, percentage of support vectors and total classification error. The sensitivity of the four sets ranged from 79% to 100%. Specificity was 100% for all sets. The total classification error ranged from 0% to 20%. The percentage of support vectors ranged from 33% to 49%. Overall, the best results were obtained with the set of parameters consisting of fetal movement, short-term variability, long-term variability, deceleration and ultrasound score. The sensitivity, specificity, percentage of support vectors and total classification error of this set were respectively 100%, 100%, 35% and 0%. This indicated our ability to separate the data into two sets (normal fetuses and pathologic fetuses), and the results highlight the excellent match with the clinical classification performed by the physicians. This work indicates the feasibility of detecting compromised fetuses and also represents an interesting method of close fetal monitoring during the entire pregnancy. PMID- 26365926 TI - Feasibility of Using Volumetric Contrast-Enhanced Ultrasound with a 3-D Transducer to Evaluate Therapeutic Response after Targeted Therapy in Rabbit Hepatic VX2 Carcinoma. AB - The aim of this study was to assess the feasibility of using dynamic contrast enhanced ultrasound (DCE-US) with a 3-D transducer to evaluate therapeutic responses to targeted therapy. Rabbits with hepatic VX2 carcinomas, divided into a treatment group (n = 22, 30 mg/kg/d sorafenib) and a control group (n = 13), were evaluated with DCE-US using 2-D and 3-D transducers and computed tomography (CT) perfusion imaging at baseline and 1 d after the first treatment. Perfusion parameters were collected, and correlations between parameters were analyzed. In the treatment group, both volumetric and 2-D DCE-US perfusion parameters, including peak intensity (33.2 +/- 19.9 vs. 16.6 +/- 10.7, 63.7 +/- 20.0 vs. 30.1 +/- 19.8), slope (15.3 +/- 12.4 vs. 5.7 +/- 4.5, 37.3 +/- 20.4 vs. 15.7 +/- 13.0) and area under the curve (AUC; 1004.1 +/- 560.3 vs. 611.4 +/- 421.1, 1332.2 +/- 708.3 vs. 670.4 +/- 388.3), had significantly decreased 1 d after the first treatment (p = 0.00). In the control group, 2-D DCE-US revealed that peak intensity, time to peak and slope had significantly changed (p < 0.05); however, volumetric DCE-US revealed that peak intensity, time-intensity AUC, AUC during wash-in and AUC during wash-out had significantly changed (p = 0.00). CT perfusion imaging parameters, including blood flow, blood volume and permeability of the capillary vessel surface, had significantly decreased in the treatment group (p = 0.00); however, in the control group, peak intensity and blood volume had significantly increased (p = 0.00). It is feasible to use DCE-US with a 3-D transducer to predict early therapeutic response after targeted therapy because perfusion parameters, including peak intensity, slope and AUC, significantly decreased, which is similar to the trend observed for 2-D DCE-US and CT perfusion imaging parameters. PMID- 26365927 TI - Alcohol consumption is associated with a lower incidence of acute myocardial infarction: results from a large prospective population-based study in Norway. AB - AIMS: Compelling evidence suggests that light-to-moderate alcohol consumption is associated with a reduced risk of acute myocardial infarction (AMI), but several issues from previous studies remain to be addressed. The aim of this study was to investigate some of these key issues related to the association between alcohol consumption and AMI risk, including the strength and shape of the association in a low-drinking setting, the roles of quantity, frequency and beverage type, the importance of confounding by medical and psychiatric conditions, and the lack of prospective data on previous drinking. METHODS: A population-based prospective cohort study of 58 827 community-dwelling individuals followed for 11.6 years was conducted. We assessed the quantity and frequency of consumption of beer, wine and spirits at baseline in 1995-1997 and the frequency of alcohol intake approximately 10 years earlier. RESULTS: A total of 2966 study participants had an AMI during the follow-up period. Light-to-moderate alcohol consumption was inversely and linearly associated with AMI risk. After adjusting for major cardiovascular disease risk factors, the hazard ratio for a one-drink increment in daily consumption was 0.72 (95% confidence interval 0.62-0.86). Accounting for former drinking or comorbidities had almost no effect on the association. Frequency of alcohol consumption was more strongly associated with lower AMI risk than overall quantity consumed. CONCLUSIONS: Light-to-moderate alcohol consumption was linearly associated with a decreased risk of AMI in a population in which abstaining from alcohol is not socially stigmatized. Our results suggest that frequent alcohol consumption is most cardioprotective and that this association is not driven by misclassification of former drinkers. PMID- 26365928 TI - Increase of serum interleukin 6 and interferon gamma is associated with the number of impulses in patients with supraventricular arrhythmias treated with radiofrequency catheter ablation. AB - BACKGROUND: Activation of the immune system plays a pathogenic role in the process of myocardial remodeling in patients with supraventricular arrhythmias. The intensity of this process is associated with the effectiveness of electrical cardioversion and radiofrequency catheter ablation (RFA). The aim of this study was to test the ability of the biochip microarray to detect immune parameters in patients with supraventricular arrhythmias undergoing RFA treatment. METHODS: We used a biochip-based microarray system to determine multiple immune parameters in a group of 35 patients who had undergone RFA for atrioventricular nodal reentry tachycardia (AVNRT), atrial flutter (AFL) and atrial fibrillation (AF). RESULTS: Before the procedure, serum IL-6 and VEGF levels were significantly increased in patients with atrial fibrillation compared to patients with AVNRT (IL-6: 6.4+/ 6.3 ng/L vs. 1.5+/-0.7 ng/L, P < 0.01; VEGF: 132.4+/-74 ng/L vs. 88.5+/-56.4 ng/L, P < 0.01). After the procedure, serum IL-6, VEGF, IFN-gamma and MCP-1 levels significantly increased compared to baseline (IL-6: 5.2+/-4.8 ng/L vs. 2.9+/-2.1 ng/L, P < 0.01; VEGF: 195.8+/-160 ng/L vs. 119.8+/- 110 ng/L, P < 0.05; IFN-gamma: 3.1+/-1.2 ng/L vs. 2.3+/-0.6 ng/L, P < 0.05; MCP-1: 104.1+/-84.5 ng/L vs. 54.5+/-50 ng/L, P < 0.05). Serum IL-6 and IFN-gamma were associated with the number of RFA applications (IL-6: r = 0.56, n 33; IFN-gamma: r = 0.47, n 33). CONCLUSIONS: This study showed that biochip-based microarray can be useful in the detection of immune activation in patients with arrhythmias and can detect myocardial injury after RF procedures. PMID- 26365929 TI - Relationship of differences in immunoglobulin heavy/light chain pairs (Hevylite), selected laboratory parameters and stratification systems in different immunochemical types of multiple myeloma. AB - BACKGROUND AND AIMS: Advances in the diagnosis and treatment of multiple myeloma (MM), place increasing demands on accurate stratification of patients as the starting point for optimal individualized therapy. The present study focused on assessing the association between HLC levels and the HLC-r to parameters of MM activity, prognosis and tumor mass volume.The objective was to assess the correlation of immunoglobulin (Ig), heavy/light chain (HLC) pairs (IgG-kappa and lambda, IgA-kappa and -lambda HLC) and the ratio of monoclonal involved-HLC (i HLC) to polyclonal uninvolved (u-HLC) Ig concentrations assessed by the Hevylite(TM) method with the free light chain kappa/lambda ratio (FLC-r), selected prognostic laboratory parameters i.e. Hb, platelets, albumin, beta2 microglobulin (beta2-M), Ca, lactate dehydrogenase (LDH), creatinine and the Durie-Salmon (D-S) and International Staging System (ISS), stages (1-3) for MM. METHODS: Hevylite assays were done on the sera of 132 MM patients at the time of diagnosis (IgG 94, IgA 38). HLC-r was calculated in the case of i-HLC-kappa from the i-HLC-kappa/u-HLC-lambda ratio and for i-HLC-lambda from the i-HLC-lambda/u HLC-kappa ratio. D-S and ISS stages were evenly distributed. RESULTS: Md IgG kappa HLC-r was 64.8 (2.7-2222) and of IgG-lambda HLC-r 49.6 (0.7-465.1), in the case of IgA-kappa, Md HLC-r was 408.9 (3.4-3966) and for IgA-lambda HLC-r the Md was 180.0 (0.1-3110). Normal levels of HLC pairs and HLC-r did not always rule out the diagnosis of MM. HLC-r correlated with FLC-r in IgG (r = 0.244, P = 0.018), but not in the IgA type. For IgG, HLC-r values were significantly different in patients with abnormal vs normal levels of Hb (P < 0.0001), albumin (P < 0.043), beta2-M (P < 0.0001) and creatinine (P = 0.034) but not thrombocyte count, Ca or LDH. For the IgA isotype, we found a significant difference in HLC-r values only for thrombocyte count (P = 0.026) and beta2-M (P = 0.016) but not for Hb, albumin, Ca, LDH or creatinine. For the IgG isotype there was a significant relationship of HLC-r index to stages 1-3 (P = 0.038) and substage A vs B (P = 0.048) according to D-S, and with high significance to stages 1-3 according to ISS (P = 0.005) and between stages 1 vs 3 (P = 0.001). For the IgA isotype, we found significant differences in HLC-r only between stages 1-3 (P = 0.025) according to D-S but not in the case of ISS. There were no significant correlations between i-HLC Ig levels and D-S or ISS stages in both IgG-kappa and lambda and IgA-kappa and lambda. Exceptions were significant differences for stages 1 vs 3 (P = 0.012) and 2 vs 3 (P = 0.017) for the IgG-lambda isotype. There were no correlations of the HLC-r and u-HLC levels for either D-S or ISS stratifications in all HLC isotypes. CONCLUSION: We found a significant positive contribution of HLC-r using the i-HLC/u-HLC ratio even in the case of i-HLC lambda i.e. i-HLC-lambda/u-HLC-kappa. Variable results for the relationship of important laboratory parameters and D-S and ISS stratifications (stage 1-3) to HLC-r values in IgG and IgA isotypes make separate interpretation of the Hevylite method results necessary in clinical practice. PMID- 26365930 TI - Long-term follow-up of posterior capsule opacification after AquaLase and NeoSoniX phacoemulsification. AB - AIM: To compare the degree of posterior capsule opacification (PCO) after AquaLase and NeoSoniX phacoemulsification methods during an 8-year follow-up period using two types of software. DESIGN: Prospective, randomized clinical trial. METHODS: AquaLase was used in the right eye and NeoSoniX in the left eye of each patient with bilateral cataract. RESULTS: Fifty patients were analyzed 1 year, 46 patients 3 years, and 37 patients 8 years after cataract surgery. Mean EPCO 2000 values were for the AquaLase group 0.324 +/- 0.305 and for the NeoSoniX group 0.298 +/- 0.341 (P = 0.53) 1 year after surgery, for the AquaLase group 0.582 +/- 0.506 and for the NeoSoniX group 0.594 +/- 0.515 (P = 0.87) 3 years after surgery, and for the AquaLase group 0.648 +/- 0.567 and for the NeoSoniX group 0.673 +/- 0.542 (P = 0.30) 8 years after surgery. The OSCA results were for the AquaLase group 0.7097 +/- 0.3778 and for the NeoSoniX group 0.8584 +/- 0.4323 (P = 0.046) 1 year after surgery, for the AquaLase group 0.9667 +/- 0.736 and for the NeoSoniX group 0.9540 +/- 0.5250 (P = 0.91) 3 years after surgery, and for the AquaLase group 1,035 +/- 0,952 and for the NeoSoniX group 1,103 +/- 0,741 (P = 0.44) 8 years after surgery. CONCLUSION: There was minimal PCO difference between these 2 approaches, AquaLase and NeoSoniX. Neither AquaLase nor NeoSoniX technique was able to prevent a natural progression of PCO. PMID- 26365931 TI - Evaluation of cytokines and soluble adhesion molecules in patients with newly diagnosed acute myeloid leukemia: the role of TNF-alpha and FLT3-ITD. AB - OBJECTIVES: Acute myeloid leukemia (AML) cells are highly resistant to therapy. The presumed molecular basis of this resistance is the effect of tumor necrosis factor alpha (TNF-alpha) and other cytokines on endothelial adhesion molecule expression. The aim of this study was to test the hypothesis that cytokines and soluble adhesion molecules correlate in AML. METHODS: Baseline serum levels of 17 cytokines and 5 soluble adhesion molecules were measured in 53 AML patients using biochip array technology. Age, leukocyte count, secondary AML, CRP, FLT3-ITD and remission were variables. Statistical analysis was performed in R version 3.1.2. RESULTS: VCAM-1 correlated with ICAM-1 (P < 0.0001), E-selectin (P < 0.0001), leukocyte count (P = 0.0005) and TNF-alpha (P = 0.0035). E-selectin correlated with leukocyte count (P < 0.0001), P-selectin (P = 0.0032) and MCP-1 (P = 0.0119). CRP correlated with IL-6 (P < 0.0001), leukocyte count negatively correlated with IL-7 (P = 0.0318). FLT3-ITD was associated with higher E-selectin (P = 0.0010) and lower IL-7 (P = 0.0252). Secondary AML patients were older. Failure of induction therapy was associated with significantly higher CRP and lower P-selectin. Leukocyte count (P < 0.0001), FLT3-ITD (P = 0.0017) and secondary AML (P = 0.0439) influenced the principal component. CONCLUSIONS: Leukemic cells can modulate the microenvironment. Cytokine, adhesion molecule levels and leukocyte count correlate in AML. Understanding these mechanisms may form the basis of novel therapeutic approaches. PMID- 26365932 TI - Insulin-like Growth Factors in a clinical setting: Review of IGF-I. AB - BACKGROUND AND AIMS: Interest in growth hormone (GH) is inextricably linked to the need for in depth understanding of the somatomedins (insulin-like growth factors) which are polypeptides structurally similar to insulin and with broad physiological activity. To date, the most commonly known is Insulin-Like Growth Factor I (IGF-I). Despite considerable current knowledge of IGF-I, however, its bioactivity is incompletely understood. Measurement of IGF-I is of the utmost importance in the diagnosis and treatment of, for example acromegaly and growth hormone deficiency. The development of recombinant IGF-I, has allowed its use in such cases. Clinical practice, however, shows that few young/adult patients will benefit from treatment with the rIGF-I, mecasermin, given the number of adverse effects found. This review focuses on current knowledge mainly related to IGF-I and the use of its recombinant form (rIGF-I) in clinical practice. Several functions of IGI-II have been elucidated but their clinical significance is unclear. PMID- 26365933 TI - Increased levels of MMP-3, MMP-9 and MPO represent predictors of in-stent restenosis, while increased levels of ADMA, LCAT, ApoE and ApoD predict bare metal stent patency. AB - AIMS: We sought to identify biochemical predictors that indicate susceptibility to in-stent restenosis (ISR) after coronary artery bare-metal stenting. METHODS: A total of 111 consecutive patients with post-percutaneous coronary intervention (PCI) in-stent restenosis of a target lesion within 12 months were matched for age, sex, vessel diameter, and diabetes with 111 controls without post-PCI ISR. Plasma or serum levels of biochemical markers were measured: matrix metalloproteinases (MMP) 2, 3, 9; myeloperoxidase (MPO); asymmetric dimethylarginine (ADMA); lipoprotein (a) (Lp[a]); apolipoproteins E and D (ApoE and D); and lecitin-cholesterol acyltransferase (LCAT). Multivariable logistic regression association tests were performed. RESULTS: Increased plasma MMP-3 (OR: 1.013; 95% CI: 1.004-1.023; P = 0.005), MMP-9 (OR: 1.014; 95% CI: 1.008-1.020; P < 0.0001) or MPO (OR: 1,003; 95% CI: 1.001-1.005; P = 0.002) was significantly associated with increased risk of ISR. Increased levels of ADMA (OR: 0.212; 95% CI: 0.054-0.827; P = 0.026), ApoE (OR: 0.924; 95% CI: 0.899-0.951; P < 0.0001), ApoD (OR: 0.919; 95% CI: 0.880-0.959; P = 0.0001), or LCAT (OR: 0.927; 95% CI: 0.902-0.952; P < 0.0001) was associated with risk reduction. No correlation was found between plasma MMP-2 or Lp (a) and ISR risk. CONCLUSIONS: Increased levels of MMP-3, MMP-9, and MPO represent predictors of ISR after bare-metal stent implantation. In contrast, increased ADMA, LCAT, and Apo E and D indicate a decreased in-stent restenosis occurrence. PMID- 26365934 TI - Abnormalities in pulmonary function in infants with high-risk congenital diaphragmatic hernia. AB - AIMS: The aim of the study was to analyze lung growth and abnormality of infant pulmonary function tests (IPFT) in congenital diaphragmatic hernia (CDH) survivors younger than three years of age with respect to unfavorable prognostic factors. METHODS: Thirty high-risk CDH survivors at the age of 1.32+/-0.54 years, body weight 9.76+/-1.25 kg were examined using IPFT: tidal breathing analysis, baby resistance/compliance, whole baby body plethysmography and rapid thoraco abdominal compression. Gore-Tex patch was used in 13% of patients (GORE group). Pulmonary hypertension was diagnosed and managed in 13% (iNO group). Standard protocols and appropriate reference values were used and obtained data were statistically analysed. RESULTS: High incidence of peripheral airway obstruction (70%), increased value of functional residual capacity (FRCp) 191.3+/-24.5 mL (126.5+/-36.9 % predicted; P < 0.0005), increased value of effective airway resistance (Reff) 1.71+/-0.93 kPa.L(-1).s (144.4+/-80.1 % predicted; P < 0.01) and decreased specific compliance of the respiratory system (Crs/kg) 14.1+/-2.3 mL.kPa.kg(-1) (i.e., 76.1+/-20.1 % predicted, P < 0.0005) was noted in infants with CDH in comparison with reference values. Increased value of FRCp was found in GORE group (165.7+/-51.9 versus 120.4+/-31.2, P < 0.02) and in iNO group (183.1+/-52.6 versus 117.8+/-25.7 mL; P < 0.0005). CONCLUSION: A high incidence of peripheral airway obstruction, an increased value of FRCp and decreased specific compliance of the respiratory system was noted in infants with CDH. Unfavorable prognostic factors (Gore-Tex patch, pulmonary hypertension) correlate with more severe alteration of pulmonary function in infants. PMID- 26365935 TI - New model of secondary cardiovascular prevention for patients after acute coronary syndromes in Poland with regard to Norwegian experiences. PMID- 26365936 TI - Study design and rationale for Optimal aNtiplatelet pharmacotherapy guided by bedSIDE genetic or functional TESTing in elective percutaneous coronary intervention patients (ONSIDE TEST): a prospective, open-label, randomised parallel-group multicentre trial (NCT01930773). AB - BACKGROUND AND AIM: High platelet reactivity (HPR) and presence of CYP2C19 loss of-function alleles are associated with higher risk for periprocedural myocardial infarction in clopidogrel-treated patients undergoing percutaneous coronary intervention (PCI). It is unknown whether personalised treatment based on platelet function testing or genotyping can prevent such complications. METHODS: The ONSIDE-TEST is a multicentre, prospective, open-label, randomised controlled clinical trial aiming to assess if optimisation of antiplatelet therapy based on either phenotyping or genotyping is superior to conventional care. Patients will be randomised into phenotyping, genotyping, or control arms. In the phenotyping group, patients will be tested with the VerifyNow P2Y12 assay before PCI, and patients with a platelet reactivity unit greater than 208 will be switched over to prasugrel, while others will continue on clopidogrel therapy. In the genotyping group, carriers of the *2 loss-of-function allele will receive prasugrel for PCI, while wild-type subjects will be treated with clopidogrel. Patients in the control arm will be treated with standard-dose clopidogrel. The primary endpoint of the study is the prevalence of periprocedural myocardial injury within 24 h after PCI in the controls as compared to the phenotyping and genotyping group. Secondary endpoints include cardiac death, myocardial infarction, definite or probable stent thrombosis, or urgent repeat revascularisation within 30 days of PCI. Primary safety outcome is Bleeding Academic Research Consortium (BARC) type 3 and 5 bleeding during 30 days of PCI. SUMMARY: The ONSIDE TEST trial is expected to verify the clinical utility of an individualised antiplatelet strategy in preventing periprocedural myocardial injury by either phenotyping or genotyping. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01930773. PMID- 26365937 TI - Stroke prevention in atrial fibrillation patients in Poland and other European countries: insights from the GARFIELD-AF registry. AB - BACKGROUND: Atrial fibrillation (AF) is the most common clinically-significant arrhythmia in the adult population, and it is a strong independent risk factor for cerebrovascular accidents. Patients with non-valvular AF are five times more likely to suffer a stroke. Despite the clear recommendations for anticoagulant therapy, many clinicians are still reluctant to provide routine oral anticoagulation to patients with AF, despite the potential clinical benefits. AIM: To compare Polish and European populations of patients with AF and the every day practice of stroke prevention in Poland and in the rest of Europe. METHODS: We analysed the baseline data from the two first cohorts of patients enrolled in the GARFIELD-AF registry (an ongoing prospective, multicentre, international registry of patients newly diagnosed with AF) in Poland and in the rest of Europe. RESULTS: Polish AF patients are generally younger (median age 67 years in both cohorts vs. 73 in cohort 1 in the rest of Europe and 72 in cohort 2), but they carry a burden of more concomitant diseases. There are some noticeable differences in stroke prevention between Poland and the rest of Europe. The use of vitamin K antagonists (VKAs) is generally higher in other European countries in both cohorts (in Poland 41.7% in cohort 1 and 36.9% in cohort 2 vs. 55.5% in cohort 1 and 41.9% in cohort 2 in the rest of Europe). Meanwhile, it is generally more common in Poland to treat patients with both VKAs and antiplatelets (in cohort 1 20.4% of patients in Poland received vs. 12.0% in the rest of Europe). A total of 5.6% of patients in cohort 1 in Poland receive no antithrombotic treatment (it means: no VKA, oral factor Xa or thrombin inhibitors, antiplatelets), meanwhile in other countries it amounts to 8.5%. The usage of non vitamin K oral anticoagulants is growing in Poland similarly to the other European countries. CONCLUSIONS: The GARFIELD-AF registry data shows how distant everyday clinical practice is from the guidelines. It shows that still in Poland, as well as in the rest of Europe, too many patients with low stroke risk are treated with anticoagulants, while too frequently patients at high stroke risk are left with no stroke prevention. Although the tendency to use non-vitamin K oral anticoagulants is growing comparably in Poland and in the rest of Europe, the proportion of patients with intermediate and high stroke risk is not growing and more patients at low stroke risk are treated with anticoagulants. PMID- 26365938 TI - Decision-making microRNAs (miR-124, -133a/b, -34a and -134) in patients with occluded target vessel in acute coronary syndrome. AB - BACKGROUND: Coronary artery occlusion does not always manifest with ST-elevation, and some patients can have patent coronary vessel. AIM: We evaluated circulating microRNA (miRNA) profiles to discriminate subjects with infarct-related artery (IRA) occlusion. METHODS AND RESULTS: Patients (n = 43) with uncomplicated acute coronary syndrome and positive troponins were classified with respect to patent vs. occluded IRA or ST-elevation vs. non-ST elevation MI (STEMI vs. NSTEMI). Expression levels of serum miRNAs (miR-1, -16, -34a, -122, -124, -208b, -133a/b, 375, and -499) were analysed. Out of 16 STEMI and 27 NSTEMI patients, IRA occlusion was noted in 12 and 15 patients, respectively. The remaining four STEMI and 12 NSTEMI patients had patent IRA. STEMI patients had higher troponin T levels and a 3.83-fold higher miR-134 expression (p < 0.025). Patients with the occluded vs. patent IRA had higher levels of miR-133a (fold change: 7.00), miR 133b (4.57), miR-34a (5.50), miR-124 (2.55), and miR-134 (3.45) but no difference in troponin T levels. Receiver operator characteristic analysis identified decision-making miRNAs in occluded vessels: miR-124 (AUC: 0.787, p < 0.001), miR 133b (AUC: 0.704, p = 0.006), and miR-134 (AUC: 0.686, p = 0.016). With respect to STEMI, only miR-134 showed a discriminating value (AUC: 0.725, p = 0.002). CONCLUSIONS: The degree of IRA occlusion determines circulating miRNA expression, and specific miRNAs may be useful in indicating patients requiring urgent coronary revascularisation. PMID- 26365939 TI - Global cardiovascular mortality risk in the adult Polish population: prospective assessment of the cohorts studied in multicentre national WOBASZ and WOBASZ Senior studies. AB - BACKGROUND AND AIM: To develop a global cardiovascular disease (CVD) mortality risk model for the Polish population and to verify these data in the context of the SCORE risk algorithm. METHODS: We analysed data obtained in two multicentre national population studies, the WOBASZ study which was conducted in 2003-2005 and included 14,769 subjects aged 20-74 years, and the WOBASZ Senior study which was conducted in 2007 and included 1096 subjects above 74 years of age. All these subjects were followed for survival status until 2012 and the cause of death was determined. The mean duration of follow-up was 8.2 years for WOBASZ study participants and about 5 years for WOBASZ Senior study participants. Overall, 1436 subjects died, including 568 due to CVD. For the purpose of our analysis of overall and CVD mortality, 15 established risk factors were selected. Survival was analysed separately in WOBASZ and WOBASZ Senior study participants. Statistical methods included descriptive statistics, Kaplan-Meier curves, Cox proportional hazard models, and the SCORE risk algorithm. Measure of incompatibility of the SCORE risk model to the Polish population was determined as the difference between mortality rates by the SCORE risk quartiles and the Cox approach. RESULTS: During the 8-year follow-up of the WOBASZ study population, mortality due to CVD was 38% among men and 31% among women. The most common causes of CVD mortality were ischaemic heart disease (IHD, 33%) followed by cerebro-vascular disease (17%) in men, and cerebrovascular disease (31%) followed by IHD (23%) in women. We found significant differences between men and women in regard to survival curves for both overall mortality and CVD mortality (p < 0.0001). For overall mortality among men and women, nearly all selected risk factors were shown to be significant in univariate analyses, except for high density lipoprotein cholesterol (HDL-C) level and the total cholesterol/HDL-C ratio in men, and smoking status in women. In multivariate analysis, independent predictors in men included age, glucose level, systolic blood pressure, and smoking status. In women, independent predictors were age, smoking status, and diabetes. During the 5-year follow-up of the WOBASZ Senior study population, mortality due to CVD was 48% among men and 58% among women. The most common cause of CVD mortality in both men and women was IHD (29% and 24%, respectively), followed by cerebrovascular disease (16% and 21%, respectively). We found significant differences between men and women in regard to survival curves for overall mortality (p < 0.0001) but not for CVD mortality (p = 0.0755). Due to the fact that survival curves for CVD mortality did not differ between men and women, we estimated the cut-off age for no survival difference in the WOBASZ study. By selecting the oldest patients and adding them to the WOBASZ Senior cohort, we obtained the cut-off age of 70 years above which the survival curves were not significantly different between men and women. In univariate analyses, independent predictors in men were age and creatinine level. These factors remained significant in multivariate analysis. In women above 74 years of age, independent predictors in univariate analyses included age, HDL-C level, creatinine level, total cholesterol/HDL-C ratio, and smoking status. Age, HDL-C level, creatinine level, and smoking status remained independent predictors of overall mortality in multivariate analysis. For CVD mortality, significant predictors were the same as for overall mortality. In women, significant predictors in uni- and multivariate analyses were age and smoking status. Overall disagreement between CVD mortality rates by the SCORE risk model and the Cox model was 5.7% in men and 2% in women. CONCLUSIONS: 1. Long-term follow-up of WOBASZ and WOBASZ Senior study participants allowed assessment of the inde pendent association of the evaluated cardiovascular risk factors with CVD mortality in the Polish population. 2. Validation of the SCORE risk algorithm to estimate individual global CVD risk in the Polish population showed a high predictive value of this algorithm. PMID- 26365940 TI - The impact of physical training on endothelial function in myocardial infarction survivors: pilot study. AB - BACKGROUND: Endothelial dysfunction (ED) may indirectly influence the outcome of patients with coronary artery disease. AIM: To assess the influence of cardiac rehabilitation (CR) on endothelial function in patients after ST-segment elevation myocardial infarction (STEMI). METHODS: Twenty-nine patients scheduled for CR were included in the study. CR began at least four weeks after STEMI and consisted of 12 or 24 training sessions. Endothelial function assessment was performed before and after CR, using reactive hyperaemia peripheral arterial tonometry. RESULTS: Before the CR, ED was diagnosed in 16 of 29 (55.2%) patients. A total of 25 patients had two assessments of endothelial function: before and after CR. In univariate analysis the factors of negative response of endothelial function to CR were: higher baseline hyperaemia index (lnRHI) (odds ratio [OR] for positive response to CR 0.01; 95% confidence interval [CI] 0.00-0.33; p = 0.01) and higher peak serum troponin I level during index hospitalisation (OR 0.97; 95% CI 0.94-1.00; p = 0.04). The independent, negative predictor of response to CR was lnRHI (OR 0.01; 95% CI 0.01-0.16; p = 0.03). Patients training for 24 sessions (n = 16) had similar lnRHI changes to those of patients training for 12 sessions (n = 9); [0.16 (-0.06)-0.30 vs. 0.10 (0.05-0.15); p = 0.44, respectively]. CONCLUSIONS: ED is a frequent abnormality in STEMI survivors. Despite the lack of statistically significant improvement of endothelial function after CR in the analysed group of patients, some factors can influence the efficacy of this type of physical activity. The best effect of CR on endothelial function was observed in patients with baseline ED. PMID- 26365941 TI - Clinical and angiographic characteristics of coronary artery disease in young adults: a single centre study. AB - BACKGROUND: Coronary artery disease (CAD) in young adults under 40 years of age is a growing medical, social, psychological and economical problem, related to the prevalence of civilization-related diseases and unhealthy lifestyle. The problem of CAD in young people has not been characterised as well as in older individuals, as the available data mostly come from case reports and small series, often related to genetic aspects and familial occurrence of the disease. AIM: To assess clinical and angiographic characteristics of young adults with CAD and to evaluate in-hospital and long-term mortality in this patient group. The study combined a retrospective and a prospective approach. METHODS: A total of 239 patients aged 40 years or younger who underwent coronary angiography (CAG) in the Swietokrzyskie Centre of Cardiology in Kielce in 2001-2008 were included in this study. Demographic characteristics, risk factor profile, laboratory test results, electrocardiographic and echocardiographic findings, CAG findings, and in-hospital mortality were assessed retrospectively in the selected groups. During the second stage of the study, clinical and mortality data were obtained prospectively in 130 patients (54.4% of the study group) during up to 5 years of follow-up. RESULTS: The mean patient age was 35.1 +/- 4.4 years. Men made up 86.2% of the study sample, and the proportion of rural area residents was 54.8%. Among young patients with acute coronary syndromes (ACS), the most common presentation (52.8%) was ST segment elevation myocardial infarction (STEMI). Angiographically normal coronary arteries were found in 37.2% of CAD patients and in 16.9% of patients with the diagnosis of ACS. The mean degree of coronary artery lumen stenosis was 75.4% in the group with significant atherosclerotic coronary lesions (50-90%) and 95.9% in the group demonstrating a critical coronary obstruction (>= 90%). Single-vessel disease was identified in 61.9% of patients with a positive result of CAG (stenosis > 50%, CORO(+) group). The most common location of significant atherosclerotic coronary lesions was the left anterior descending artery (61.6%) followed by the right coronary artery (27.4%). The most prevalent conventional cardiovascular risk factors were lipid abnormalities, cigarette smoking and an increased body mass index >= 25 kg/m2, followed by a family history of CAD and hypertension. The proportion of patients with abnormal lipid profile, cigarette smoking and overweight or obesity was particularly high in the CORO(+) group (85.6%, 83.9%, and 64.4%, respectively). In-hospital mortality rate was low, at 0.7% among ACS patients. Long-term mortality during up to 5 years of follow-up was not so favourable, at 7.75% in ACS patients and 8.5% in the CORO(+) group. CONCLUSIONS: The population of young patients with CAD is predominantly male, rural, and characterised by a low socio economic status. The aetiology of CAD in this patient group differs significantly from that in older patients and it is often associated with an unhealthy lifestyle related to rapid civilization changes. The rates of CAD risk factors in young adults are high and the most important risk factors are dyslipidaemia, smoking, and overweight/obesity. Single vessel disease and STEMI presentation were predominant in young patients. Short-term prognosis in young ACS patients is excellent, but long-term prognosis is significantly worse. Further studies on CAD in young adults are warranted, particularly in larger patient populations. PMID- 26365942 TI - The prognostic value of admission mean platelet volume to platelet count ratio in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. AB - BACKGROUND: Mean platelet volume to platelet count (MPV/Plt) ratio has been demonstrated to be a good indicator of long-term mortality in patients with non ST-segment elevation myocardial infarction (NSTEMI). However, the prognostic value of MPV/Plt in ST-elevation myocardial infarction (STEMI) is not reported. AIM: To determine whether the MPV/Plt ratio on admission has any predictive value for major adverse cardiac events including short- and long-term mortality in STEMI. METHODS: In this prospective study, 470 STEMI patients who underwent primary percutaneous coronary intervention (PCI) were enrolled. The patients were divided into three tertiles based on the MPV/Plt ratio on admission. The first tertile (n = 149) was defined as MPV/Plt ratio <= 0.029, second tertile (n = 154) 0.029-0.038, and third tertile (n = 159) >= 0.038. Primary clinical outcomes consisted of the sum of cardiovascular (CV) mortality, non-fatal re-infarction, and stroke. Secondary clinical outcomes were CV mortality, non-fatal re infarction, target-vessel revascularisation, stroke, and advanced heart failure. RESULTS: There was no difference between study groups regarding the primary (p > 0.05) and the secondary outcomes (p > 0.05) except for one-year non-fatal re infarction rate, which was found to be significantly higher in the highest MPV/Plt ratio group (p = 0.045). Age, Killip class > 1, and left ventricular ejection fraction were found to be independent predictors of long-term CV mortality in multivariate analysis (p = 0.009, p = 0.035, and p < 0.001, respectively). CONCLUSIONS: While the MPV/Plt ratio was demonstrated to be associated with one-year non-fatal re-infarction, it was not related to in hospital, one-month, and one-year CV mortality in patients with STEMI, who underwent primary PCI. PMID- 26365943 TI - Clinical characteristics and predictors of one-year outcome of heart failure patients with atrial fibrillation compared to heart failure patients in sinus rhythm. AB - BACKGROUND: Atrial fibrillation (AF) frequently coexists with heart failure (HF). AIM: To assess clinical characteristics and to identify predictors of one-year outcome of patients hospitalised for HF, depending on whether they were in sinus rhythm (SR) or had AF. METHODS: The study included Polish patients hospitalised for HF, participating in the Heart Failure Pilot Survey of the European Society of Cardiology, who were followed for 12 months after discharge. Patients with paced heart rhythm were excluded from the study. The primary endpoint was all cause death at 12 months. RESULTS: The final analysis included 587 patients. AF occurred in 215 (36.6%) patients. Compared to patients in SR, patients with AF were older, more often had a history of previous HF hospitalisation, were characterised by a higher New York Heart Association (NYHA) class, higher heart rate, and lower diastolic blood pressure at hospital admission, and had higher serum creatinine and lower haemoglobin concentration at admission. In-hospital mortality was higher in AF patients compared to SR patients (5.1% vs. 2.4%, respectively), but the difference did not reach statistical significance (p = 0.1). The primary endpoint occurred in 41 of 215 AF patients (19.1%) and in 40 of 372 SR patients (10.8%; p = 0.006). In a multivariate analysis, predictors of the primary endpoint in AF patients were: higher NYHA class at hospital admission (p = 0.02), higher admission heart rate (p = 0.04), lower admission serum sodium concentration (p = 0.0001), and higher heart rate at discharge (p = 0.01). In patients with SR, independent predictors of the primary endpoint included: older age (p = 0.007), lower serum sodium concentration at admission (p = 0.0006), and higher heart rate at discharge (p = 0.008). CONCLUSIONS: Patients with HF and concomitant AF differ significantly from HF patients in SR. In the studied group of real-world HF patients, serum sodium concentration at hospital admission and heart rate at hospital discharge were independent prognostic factors in patients with AF and in patients in SR. In contrast to SR patients, heart rate at hospital admission in AF patients was also predictive of long-term mortality. PMID- 26365944 TI - Pannorin B, a new naphthopyrone from an endophytic fungal isolate of Penicillium sp. PMID- 26365945 TI - Enhanced UV Emission From Silver/ZnO And Gold/ZnO Core-Shell Nanoparticles: Photoluminescence, Radioluminescence, And Optically Stimulated Luminescence. AB - The optical properties of core-shell nanoparticles consisting of a ZnO shell grown on Ag and Au nanoparticle cores by a solution method have been investigated. Both the ZnO/Ag and ZnO/Au particles exhibit strongly enhanced near band-edge UV emission from the ZnO when excited at 325 nm. Furthermore, the UV intensity increases with the metal nanoparticle concentration, with 60-fold and 17-fold enhancements for the ZnO/Ag and ZnO/Au, core-shell nanoparticles respectively. Accompanying the increase in UV emission, there is a corresponding decrease in the broad band defect emission with nanoparticle concentration. Nonetheless, the broad band luminescence increases with laser power. The results are consistent with enhanced exciton emission in the ZnO shells due to coupling with surface plasmon resonance of the metal nanoparticles. Luminescence measurements during and after exposure to X-rays also exhibit enhanced UV luminescence. These observations suggest that metal nanoparticles may be suitable for enhancing optical detection of ionizing radiation. PMID- 26365946 TI - Risk factors and consequences of perioperative reoperation in patients undergoing pulmonary resection surgery. AB - BACKGROUND: Perioperative reoperation is generally agreed to be necessary for the management of particular, severe complications. Understanding the incidence and predictors of perioperative reoperation enables surgeons to improve surgery quality. The objective of this study is to investigate the incidence, risk factors, and consequences of perioperative reoperation after pulmonary resection. METHODS: Data from patients who underwent perioperative reoperation after pulmonary resection surgery over the past 6 years in our department were reviewed retrospectively. A propensity score-matched analysis was performed to identify the association between reoperation and clinical outcomes. Univariate and multivariate analysis were used to analyze independent risk factors for the occurrence of reoperation. RESULTS: Overall, 19,304 patients with various lung diseases who underwent pulmonary resection surgeries were analyzed retrospectively, in which 195 patients (1.01%) required reoperation for severe perioperative complications. The leading cause for reoperation was hemorrhage in 143 (73.33%) patients, followed by bronchopleural fistula in 22 patients (11.28%). Further indications for reoperation were chyle leak, bronchial esophageal fistula, empyema, pulmonary congestion, air leak, and femoral artery embolism. The mortality of reoperation was 5.13% (10/195), with the highest (33.33%) among bronchial esophageal fistula and empyema. Patients undergoing reoperation had a higher mortality at hospital discharge, a longer duration of hospital stay, and a lesser incidence of postoperative transfusion (P < .05). Logistic regression indicated that patients with comorbidity, operative approach of open thoracotomy, and location of upper lobe were independent risk factors for the occurrence of early reoperation that performed within 24 hours (P < .05); however, operative approach showed no significance in terms of reoperation that happened beyond 24 hours (P = .087). CONCLUSION: The incidence of perioperative reoperation after pulmonary resection surgery is low and is mainly related to technical issues from the initial operation. The most common complication is hemorrhage, and the mortality of reoperation in bronchial esophageal fistula and empyema is higher than in others. Patients undergoing reoperation had a higher mortality at hospital discharge, a longer duration of hospital stay, and a lesser incidence of postoperative transfusion. Preoperative comorbidity, operative approach of open thoracotomy, and location of upper lobe were independent risk factors for the occurrence of early perioperative reoperation that was performed within 24 hours; approach of surgery was not significant in terms of reoperation that happened beyond 24 hours. PMID- 26365947 TI - The role of vitamin D in post-thyroidectomy hypocalcemia: Still an enigma. AB - BACKGROUND: There is conflicting evidence regarding the role of vitamin D deficiency in the development of post-thyroidectomy hypocalcemia. Recent reports show postoperative parathormone (PTH) is unreliable in predicting post thyroidectomy hypocalcemia in vitamin D deficient patients. We conducted this study to analyze the role of vitamin D status in the development of post thyroidectomy hypocalcemia and to evaluate its effect on the predictability of PTH as a marker for post-thyroidectomy hypocalcemia. METHOD: A retrospective review of prospectively collected data of patients undergoing thyroidectomy between August 2007 to September 2013 (n = 150) was performed. Results of preoperative calcium, albumin, vitamin D, PTH and postoperative calcium, albumin, and PTH were collated. Patients were divided into 2 groups based on their vitamin D status: group A, vitamin D >= 20 ng/mL and group B, vitamin D < 20 ng/mL. RESULTS: Vitamin D deficiency was present in 80 (53.3%) patients and post thyroidectomy hypocalcemia developed in 67 (44.7%). The incidence of postoperative hypocalcemia was similar in both the groups (48.6% and 41.3%, respectively). Vitamin D status was not associated with the development of post thyroidectomy hypocalcemia (P = .23). Postoperative PTH of <8 pg/mL was strongly associated with the development of hypocalcemia in both the groups (P = .0002 and .0045, respectively). The area under the receiver operator characteristic curve in group B (0.68) was less than in group A (0.76; P = .41). CONCLUSION: The majority of patients were vitamin D deficient in this cohort, but this did not increase the risk of post-thyroidectomy hypocalcemia, nor did it interfere with the predictability of PTH as a marker of post-thyroidectomy hypocalcemia. PMID- 26365948 TI - Abdominal emergencies in cancer patients: Which criteria to decide for surgery? PMID- 26365949 TI - Accuracy of scoring systems for suspected choledocholithiasis. PMID- 26365950 TI - Development of a model to predict breast cancer survival using data from the National Cancer Data Base. AB - BACKGROUND: With the large amounts of data on patient, tumor, and treatment factors available to clinicians, it has become critically important to harness this information to guide clinicians in discussing a patient's prognosis. However, no widely accepted survival calculator is available that uses national data and includes multiple prognostic factors. Our objective was to develop a model for predicting survival among patients diagnosed with breast cancer using the National Cancer Data Base (NCDB) to serve as a prototype for the Commission on Cancer's "Cancer Survival Prognostic Calculator." PATIENTS AND METHODS: A retrospective cohort of patients diagnosed with breast cancer (2003-2006) in the NCDB was included. A multivariable Cox proportional hazards regression model to predict overall survival was developed. Model discrimination by 10-fold internal cross-validation and calibration was assessed. RESULTS: There were 296,284 patients for model development and internal validation. The c-index for the 10 fold cross-validation ranged from 0.779 to 0.788 after inclusion of all available pertinent prognostic factors. A plot of the observed versus predicted 5 year overall survival showed minimal deviation from the reference line. CONCLUSION: This breast cancer survival prognostic model to be used as a prototype for building the Commission on Cancer's "Cancer Survival Prognostic Calculator" will offer patients and clinicians an objective opportunity to estimate personalized long-term survival based on patient demographic characteristics, tumor factors, and treatment delivered. PMID- 26365951 TI - Translation and cultural adaptation of the Manchester-Oxford Foot Questionnaire (MOXFQ) into Persian language. AB - PURPOSE: In this study, we aimed to translate and test the validity and reliablity of the Persian version of the Manchester-Oxford Foot Questionnaire in foot and ankle patients. METHODS: We translated the Manchester-Oxford Foot Questionnaire to Persian language according to the accepted guidelines, then assessed the psychometric properties including the validity and reliability on 308 patients with long-standing foot and ankle problems. To test the reliability, we calculated the intra-class correlation coefficient (ICC) for test-retest reliability and measured Cronbach's alpha to test the internal consistency. To test the construct validity of the Manchester-Oxford Foot Questionnaire we also administered the Short-Form 36 to patients. RESULTS: Construct validity was supported by significant correlation with SF36 subscales except for pain subscale of the persian MOXFQ with mental health of the SF36 (r=0.207). Intraclass correlation coefficient was 0.79 for the total MOXFQ and ranged from 0.83 to 0.89 for the three subscales. Cronbach's alpha for pain, walking/standing, and social interaction was 0.86, 0.88, and 0.89, respectively, and was 0.79 for the total MOXFQ showing good internal consistency in each domain. CONCLUSION: The Persian Manchester-Oxford Foot Questionnaire health scoring system is a valid and reliable patient-reported instrument for foot and ankle problems. PMID- 26365952 TI - Waptia revisited: Intimations of behaviors. AB - The middle Cambrian taxon Waptia fieldensis offers insights into early evolution of sensory arrangements that may have supported a range of actions such as exploratory behavior, burrowing, scavenging, swimming, and escape, amongst others. Less elaborate than many modern pancrustaceans, specific features of Waptia that suggest a possible association with the pancrustacean evolutionary trajectory, include mandibulate mouthparts, a single pair of antennae, reflective triplets on the head comparable to ocelli, and traces of brain and optic lobes that conform to the pancrustacean ground pattern. This account revisits an earlier description of Waptia to further interpret the distribution of its overall morphology and receptor arrangements in the context of plausible behavioral repertoires. PMID- 26365953 TI - Perirhinal Cortex mGlu5 Receptor Activation Reduces Relapse to Methamphetamine Seeking by Restoring Novelty Salience. AB - Rats that have self-administered methamphetamine (meth) under long access, but not short access, conditions do not recognize novel objects. The perirhinal cortex is critical for novelty detection, and perirhinal metabotropic glutamate 5 receptors (mGlu5) are downregulated after long-access meth. The novel positive allosteric modulator (PAM) 1-(4-(2,4-difluorophenyl) piperazin-1-yl)-2-((4 fluorobenzyl)oxy)-ethanone, or DPFE, demonstrates improved solubility compared with other mGlu5 PAMs, thus allowing brain-site-specific pharmacological studies. Infusion of DPFE into perirhinal cortex restored novel object recognition in long access meth rats. To investigate the impact of these cognitive enhancing effects on relapse, we tested the effects of DPFE infusions into perirhinal cortex on meth-seeking under two different test conditions. In the standard cue relapse test, perirhinal DPFE infusions did not alter meth-seeking in the presence of meth cues. However, in a novel cue relapse test, wherein animals were allowed to allocate responding between a novel cue and meth-conditioned cue, perirhinal DPFE infusions shifted the pattern of responding in long-access rats toward a profile resembling short-access rats, which respond equally for novel and meth cues. Perirhinal mGlu5 are thus a promising pharmacological target for the restoration of cognitive function in meth addicts. Targeting these receptors may also reduce relapse, particularly in situations where novel stimuli compete with conditioned stimuli for control over meth seeking. PMID- 26365954 TI - Daily Exposure to Sucrose Impairs Subsequent Learning About Food Cues: A Role for Alterations in Ghrelin Signaling and Dopamine D2 Receptors. AB - The prevalence of hedonic foods and associated advertising slogans has contributed to the rise of the obesity epidemic in the modern world. Research has shown that intake of these foods disrupt dopaminergic systems. It may be that a disruption of these circuits produces aberrant learning about food-cue relationships. We found that rodents given 28 days of intermittent access to sucrose exhibited a deficit in the ability to block learning about a stimulus when it is paired in compound with food and another stimulus that has already been established as predictive of the food outcome. This deficit was characterized by an approach to a cue signaling food delivery that is usually blocked by prior learning, an effect dependent on dopaminergic prediction-error signaling in the midbrain. Administering the D2 agonist quinpirole during learning restored blocking in animals with a prior history of sucrose exposure. Further, repeated central infusions of ghrelin produced a deficit in blocking in the same manner as sucrose exposure. We argue that changes in dopaminergic systems resulting from sucrose exposure are mediated by a disruption of ghrelin signaling as rodents come to anticipate delivery of the highly palatable sucrose outside of normal feeding schedules. This suggestion is supported by our finding that both sucrose and ghrelin treatments resulted in increases in amphetamine induced locomotor responding. Thus, for the first time, we have provided evidence of a potential link between alterations in D2 receptors caused by the intake of hedonic foods and aberrant learning about cue-food relationships capable of promoting inappropriate feeding habits. In addition, we have found preliminary evidence to suggest that this is mediated by changes in ghrelin signaling, a finding that should stimulate further research into modulation of ghrelin activity to treat obesity. PMID- 26365955 TI - Clinical Characteristics and Risk Factors of Left Ventricular Thrombus after Acute Myocardial Infarction: A Matched Case-control Study. AB - BACKGROUND: Left ventricular thrombus (LVT) is reported to be a common complication in acute myocardial infarction (AMI) patients. And it has the potential to cause systemic embolism. This retrospective study was to present the current situation of LVT in clinical practice, as well as to evaluate the clinical characteristics and the risk factors of LVT after AMI. METHODS: LVT cases (n = 96) were identified from 13,732 AMI (non-ST elevation myocardial infarction was excluded) patients in Fuwai Hospital's electronic medical records system from January 2003 to January 2013. The controls (n = 192) were gender- and age-matched AMI patients without LVT during this period. A conditional logistic regression (fitted by the Cox model) was performed to identify the independent risk factors. RESULTS: The incidence of LVT after AMI was 0.7%. Univariate analysis indicated that the anterior myocardial infarction (especially extensive anterior myocardial infarction), lower left ventricular ejection fraction (LVEF), LVEF <=40%, severe regional wall motion abnormalities (RWMA), pericardial effusion, and left ventricular aneurysm were all related to LVT after AMI. The independent risk factors obtained from the conditional logistic regression analysis were lower LVEF (odds ratio (OR) = 0.891, 95% confidence interval (CI ): 0.828-0.960), extensive anterior myocardial infarction (OR = 6.403, 95% CI: 1.769 23.169), severe RWMA (OR = 7.348, 95% CI: 1.323-40.819), and left ventricular aneurysm (OR = 6.955, 95% CI: 1.673-28.921). CONCLUSIONS: This study indicated that lower LVEF, extensive anterior myocardial infarction, severe RWMA, and left ventricular aneurysm were independent risk factors of LVT after AMI. It also suggested that further efforts are needed for the LVT diagnosis after AMI in clinical practice. PMID- 26365956 TI - Incidence and Risk Factors of Obstetric Anal Sphincter Injuries after Various Modes of Vaginal Deliveries in Chinese Women. AB - BACKGROUND: Obstetric anal sphincter injuries (OASIS) can cause an adverse impact on women's physical and mental health. There was lack of published data in Chinese population particularly on studying the risk of OASIS for nonrotational outlet forceps. This study was to determine the incidence and risk factors of OASIS. METHODS: This is a retrospective cohort study carried out in a tertiary referral hospital in Hong Kong. The control group was selected randomly. Univariate and multivariate logistic regression analysis was performed to evaluate the influence of potential risk factors on OASIS. This study reviewed the obstetric records of OASIS women and random control from January 2011 to June 2014. Univariate and multivariate logistic regression analysis was performed to evaluate the influence of potential risk factors on OASIS. RESULTS: Of 15,446 women delivered, 49 had OASIS. The percentage of OASIS increased from 0.3% (2011) to 0.38% (2014). There was an increasing trend of OASIS in attempted spontaneous vaginal delivery without episiotomy (P < 0.01), but it did not increase the OASIS risk (P = 0.46). Univariate analysis of 49 cases and 438 control subjects showed that forceps delivery (odds ratio [OR] =8.73, P < 0.01), prolong second stage of labor (OR = 1.43, P < 0.01) increased the risk for OASIS. In multivariate regression models, only forceps delivery (OR = 6.28, P < 0.01) proved to be independent risk factor. CONCLUSIONS: The incidence of OASIS in Chinese women was increased after 2012, but still lower than the reported figures in the literature. Outlet forceps delivery could be a possible associated risk factor. PMID- 26365957 TI - Prevalence and Risk Factors of Atrial Fibrillation in Chinese Elderly: Results from the Chinese Longitudinal Healthy Longevity Survey. AB - BACKGROUND: Prevalence of atrial fibrillation (AF) is increasing as the world ages. AF is associated with higher risk of mortality and disease, including stroke, hypertension, heart failure, and dementia. Prevalence of AF differs with each population studied, and research on non-Western populations and the oldest old is scarce. METHODS: We used data from the 2012 wave of the Chinese Longitudinal Healthy Longevity Survey, a community-based study in eight longevity areas in China, to estimate AF prevalence in an elderly Chinese population (n = 1418, mean age = 85.6 years) and to identify risk factors. We determined the presence of AF in our participants using single-lead electrocardiograms. The weighted prevalence of AF was estimated in subjects stratified according to age groups (65-74, 75-84, 85-94, 95 years and above) and gender. We used logistic regressions to determine the potential risk factors of AF. RESULTS: The overall prevalence of AF was 3.5%; 2.4% of men and 4.5% of women had AF (P < 0.05). AF was associated with weight extremes of being underweight or overweight/obese. Finally, advanced age (85-94 years), history of stroke or heart disease, low high density lipoprotein levels, low triglyceride levels, and lack of regular physical activity were associated with AF. CONCLUSIONS: In urban elderly, AF prevalence increased with age (P < 0.05), and in rural elderly, women had higher AF prevalence (P < 0.05). Further exploration of population-specific risk factors is needed to address the AF epidemic. PMID- 26365958 TI - Long-term Efficacy of Subthalamic Nucleus Deep Brain Stimulation in Parkinson's Disease: A 5-year Follow-up Study in China. AB - BACKGROUND: Subthalamic nucleus deep brain stimulation (STN DBS) is effective against advanced Parkinson's disease (PD), allowing dramatic improvement of Parkinsonism, in addition to a significant reduction in medication. Here we aimed to investigate the long-term effect of STN DBS in Chinese PD patients, which has not been thoroughly studied in China. METHODS: Ten PD patients were assessed before DBS and followed up 1, 3, and 5 years later using Unified Parkinson's Disease Rating Scale Part III (UPDRS III), Parkinson's Disease Questionnatire-39, Parkinson's Disease Sleep Scale-Chinese Version, Mini-mental State Examination, Montreal Cognitive Assessment, Hamilton Anxiety Scale and Hamilton Depression Scale. Stimulation parameters and drug dosages were recorded at each follow-up. Data were analyzed using the ANOVA for repeated measures. RESULTS: In the "off" state (off medication), DBS improved UPDRS III scores by 35.87% in 5 years, compared with preoperative baseline (P < 0.001). In the "on" state (on medication), motor scores at 5 years were similar to the results of preoperative levodopa challenge test. The quality of life is improved by 58.18% (P < 0.001) from baseline to 3 years and gradually declined afterward. Sleep, cognition, and emotion were mostly unchanged. Levodopa equivalent daily dose was reduced from 660.4 +/- 210.1 mg at baseline to 310.6 +/- 158.4 mg at 5 years (by 52.96%, P < 0.001). The average pulse width, frequency and amplitude at 5 years were 75.0 +/- 18.21 MUs, 138.5 +/- 19.34 Hz, and 2.68 +/- 0.43 V, respectively. CONCLUSIONS: STN DBS is an effective intervention for PD, although associated with a slightly diminished efficacy after 5 years. Compared with other studies, patients in our study required lower voltage and medication for satisfactory symptom control. PMID- 26365959 TI - Role of Gonadotropin-releasing Hormone Stimulation Test in Diagnosing Gonadotropin Deficiency in Both Males and Females with Delayed Puberty. AB - BACKGROUND: Delayed puberty can result either from constitutional delay of growth and puberty (CDP) or idiopathic hypogonadotropic hypogonadism (IHH). Gonadotropin releasing hormone (GnRH) stimulation test has been generally accepted as a current method for diagnosing delayed puberty. The objective of this research was to assess the cut-off values and the efficacy of GnRH stimulation test in the diagnosis of delayed puberty in both males and females. METHODS: A study of 91 IHH, 27 CDP patients, 6 prepubertal children, and 20 pubertal adults was undertaken. Blood samples were obtained at 0, 30, 60, and 120 min after GnRH administration and the levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH) were measured. For each parameter, the sensitivities and specificities were estimated, and the receiver operating characteristic (ROC) curves were constructed. RESULTS: The ROC curves indicated that a serum basal LH <0.6 IU/L or peak LH <9.74 IU/L resulted in moderate sensitivity (73.8% or 80.0%) and specificity (90.9% or 86.4%) in the diagnosis of HH in males. Serum basal LH <0.85 IU/L or basal FSH <2.43 IU/L resulted in moderate sensitivity (80.0% or 100.0%) and specificity (75.0% or 50.0%) in the diagnosis of HH in females. CONCLUSIONS: Our data suggest that isolated use of the gonadorelin stimulation test is almost sufficient to discriminate between HH and CDP in males, but unnecessary in females. The most useful predictor is serum basal or peak LH to differentiate these two disorders in males, but serum basal LH or FSH in females. PMID- 26365961 TI - Assessing Cardiovascular Health Using Life's Simple 7 in a Chinese Population Undergoing Stroke Prevention. AB - BACKGROUND: The American Heart Association/American Stroke Association proposed a metric called Life's Simple 7 (LS7) to define cardiovascular health (CVH). The presence of a large number of ideal components of CVH is associated with lower cardiovascular disease and all-cause mortality. We aimed to assess CVH using LS7 in a Chinese population undergoing primary and secondary stroke prevention. METHODS: Patients with either ischemic stroke or cardiovascular risk factors were enrolled in the study from October 2010 to July 2013. LS7 components were scored as poor (0 points), intermediate (1 point), or ideal (2 points). The overall LS7 score was categorized as inadequate (0-4), average (5-9), or optimal (10-14) CVH. The Chi-square test, Mann-Whitney U-test, and Kruskal-Wallis test were used. RESULTS: In total, 706 patients were enrolled. (1) The distribution of the overall LS7 score (n = 255) indicated that 9.4%, 82.4%, and 8.2% of the patients had inadequate, average, and optimal CVH, respectively. The proportion of patients with optimal CVH undergoing secondary stroke prevention was lower than that for patients undergoing primary stroke prevention (3.8% vs. 12.8%, P = 0.005). The vast majority of participants (76.1%) presented with <=2 ideal health components. (2) The proportions of patients with poor, intermediate, and ideal status, respectively, for the following LS7 components were assessed : t0 otal cholesterol (n = 275; 5.1%, 73.8%, and 21.1%), blood pressure (n = 351; 32.5%, 59.0%, and 8.5%), blood glucose (n = 280; 9.3%, 39.6%, and 51.1%), physical activity (n = 540; 90.7%, 8.7%, and 0.6%), diet (n = 524; 0.2%, 92.4%, and 7.4%), smoking (n = 619; 20.7%, 2.9%, and 76.4%), and body mass index (n = 259; 6.6%, 35.5%, and 57.9%). CONCLUSIONS: Few Chinese patients undergoing stroke prevention had optimal CVH (determined using LS7). Additionally, fewer patients undergoing secondary prevention had optimal CVH than those undergoing primary prevention. In particular, physical activity and diet status in this population require improvement. PMID- 26365960 TI - Therapeutic Effects of Sodium Hyaluronate on Ocular Surface Damage Induced by Benzalkonium Chloride Preserved Anti-glaucoma Medications. AB - BACKGROUND: Long-term use of benzalkonium chloride (BAC)-preserved drugs is often associated with ocular surface toxicity. Ocular surface symptoms had a substantial impact on the glaucoma patients' quality of life and compliance. This study aimed to investigate the effects of sodium hyaluronate (SH) on ocular surface toxicity induced by BAC-preserved anti-glaucoma medications treatment. METHODS: Fifty-eight patients (101 eyes), who received topical BAC-preserved anti glaucoma medications treatment and met the severe dry eye criteria, were included in the analysis. All patients were maintained the original topical anti-glaucoma treatment. In the SH-treated group (56 eyes), unpreserved 0.3% SH eye drops were administered with 3 times daily for 90 days. In the control group (55 eyes), phosphate-buffered saline were administered with 3 times daily for 90 days. Ocular Surface Disease Index (OSDI) questionnaire, break-up time (BUT) test, corneal fluorescein staining, corneal and conjunctival rose Bengal staining, Schirmer test, and conjunctiva impression cytology were performed sequentially on days 0 and 91. RESULTS: Compared with the control group, SH-treated group showed decrease in OSDI scores (Kruskal-Wallis test: H = 38.668, P < 0.001), fluorescein and rose Bengal scores (Wilcoxon signed-ranks test: z = -3.843, P < 0.001, and z = -3.508, P < 0.001, respectively), increase in tear film BUT (t-test: t = 10.994, P < 0.001) and aqueous tear production (t-test: t = -10.328, P < 0.001) on day 91. The goblet cell density was increased (t-test: t = -9.981, P < 0.001), and the morphology of the conjunctival epithelium were also improved after SH treatment. CONCLUSIONS: SH significantly improved both symptoms and signs of ocular surface damage in patients with BAC-preserved anti-glaucoma medications treatment. SH could be proposed as a new attempt to reduce ocular surface toxicity, and alleviate symptoms of ocular surface damage in BAC-preserved anti glaucoma medications treatment. PMID- 26365962 TI - Survival Outcome of Squamous Cell Carcinoma Arising from Sinonasal Inverted Papilloma. AB - BACKGROUND: Sinonasal inverted papilloma (IP) is a rare benign tumor of the nasal cavities and paranasal sinuses. It is destructive or bone-remodeling, tends to recur after surgical resection, and has a significant malignant potential. The present study aimed to perform a retrospective analysis of patients with squamous cell carcinoma (SCC) arising from IP, including characteristics, survival outcome, and predictors of associated malignancy. METHODS: The medical records of 213 patients diagnosed with IP from January 1970 to January 2014 were retrospectively reviewed. Eighty-seven patients were diagnosed with SCC/IP; their clinical characteristics, treatments, and survival outcomes were analyzed. RESULTS: Of the 87 patients with SCC/IP, the 5- and 10-year overall survival outcomes were 39.6% and 31.8%, respectively. Twenty-nine of these patients received surgery and 58 received combined surgery and radiation. Of the patients with stages III-IV, the 5-year survival rate was 30.7% for those treated with surgery only and 39.9% for those given the combination treatment (P = 0.849). Factors associated with significantly poor prognosis were advanced-stage, metachronous tumors, or with cranial base and orbit invasion. Age, synchronous or metachronous tumors, and pathological stage were independent risk factors for mortality, shown by multivariate analysis. CONCLUSION: Patients with SCC/IP had low overall survival outcomes. Advanced age, stage, and metachronous tumors are the main factors affecting prognosis. Treatment planning should consider high risk factors to improve survival outcome. PMID- 26365963 TI - Validity of Chinese Version of the Composite International Diagnostic Interview 3.0 in Psychiatric Settings. AB - BACKGROUND: The Composite International Diagnostic Interview-3.0 (CIDI-3.0) is a fully structured lay-administered diagnostic interview for the assessment of mental disorders according to ICD-10 and Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria. The aim of the study was to investigate the concurrent validity of the Chinese CIDI in diagnosing mental disorders in psychiatric settings. METHODS: We recruited 208 participants, of whom 148 were patients from two psychiatric hospitals and 60 healthy people from communities. These participants were administered with CIDI by six trained lay interviewers and the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I, gold standard) by two psychiatrists. Agreement between CIDI and SCID-I was assessed with sensitivity, specificity, positive predictive value and negative predictive value. Individual-level CIDI-SCID diagnostic concordance was evaluated using the area under the receiver operator characteristic curve and Cohen's K. RESULTS: Substantial to excellent CIDI to SCID concordance was found for any substance use disorder (area under the receiver operator characteristic curve [AUC] = 0.926), any anxiety disorder (AUC = 0.807) and any mood disorder (AUC = 0.806). The concordance between the CIDI and the SCID for psychotic and eating disorders is moderate. However, for individual mental disorders, the CIDI SCID concordance for bipolar disorders (AUC = 0.55) and anorexia nervosa (AUC = 0.50) was insufficient. CONCLUSIONS: Overall, the Chinese version of CIDI-3.0 has acceptable validity in diagnosing the substance use disorder, anxiety disorder and mood disorder among Chinese adult population. However, we should be cautious when using it for bipolar disorders and anorexia nervosa. PMID- 26365964 TI - Interaction of Polymorphisms of Resistin Gene Promoter -420C/G, Glutathione Peroxidase -1 Gene Pro198Leu and Cigarette Smoking in Nonalcoholic Fatty Liver Disease. AB - BACKGROUND: Many studies have suggested that cigarette smoking and polymorphisms of resistin and glutathione peroxidase-1 (GPx-1) genes are closely correlated with the pathogenesis of nonalcoholic fatty liver disease (NAFLD). However, few reports have investigated these associations with respect to NAFLD susceptibility. We, therefore, examined the distribution of polymorphisms in GPx 1 and resistin genes in NAFLD patients and healthy controls and analyzed the relationship between these polymorphisms and smoking status. METHODS: Nine hundred NAFLD patients and 900 healthy controls were selected, and the genetic polymorphisms of resistin gene promoter-420C/G and GPx-1 gene Pro198Leu were analyzed by polymorphism-polymerase chain reaction (PCR) in DNA extracted from peripheral blood leukocytes. Interactions between the two mutants and the gene environment interaction with cigarette smoking were also analyzed. RESULTS: Genotype frequencies of -420C/G (GG) and Pro198Leu (LL) were significantly higher in NAFLD cases (49.56% and 50.11%, respectively) compared with healthy controls (23.67% and 24.22%, respectively) (P = 0.0069; P = 0.0072). Moreover, the risk of NAFLD with -420C/G (GG) was significantly higher than in controls (odds ratio [OR] =3.1685, 95% confidence interval (CI) =1.9366-5.2073). Individuals carrying Pro198Leu (LL) had a high risk of NAFLD (OR = 3.1424, 95% CI = 1.7951-5.2367). Combined analysis of the polymorphisms showed that the -420C/G (GG)/Pro198Leu (LL) genotype was significantly more common in the NAFLD group than in the control group (39.44% vs. 12.78%, respectively, P = 0.0054), while individuals with -420C/G (GG)/Pro198Leu (LL) had a high risk of NAFLD (OR = 5.0357, 95% CI = 3.1852-7.8106). Moreover, the cigarette smoking rate in the NAFLD group was significantly higher than in the control group (OR = 1.8990, P = 0.0083 in the smoking index (SI) <=400 subgroup; OR = 5.0937, P = 0.0051 in the SI >400 subgroup), and statistical analysis suggested a positive interaction between cigarette smoking and -420C/G (GG) (gamma = 5.6018 in the SI <=400 subgroup; gamma = 4.4770 in the SI >400 subgroup) and Pro198Leu (LL) (gamma = 5.7715 in the SI <=400 subgroup; gamma = 4.5985 in the SI >400 subgroup) in increasing the risk of NAFLD. CONCLUSION: NAFLD risk factors include -420C/G (GG), Pro198Leu (LL) and cigarette smoking, and these three factors have a significant additive effect on NAFLD risk. PMID- 26365965 TI - A Special Electroencephalography Pattern Might Help in the Diagnosis of Antibody positive Encephalitis. AB - BACKGROUND: Patterns observed with electroencephalography (EEG) for patients who have encephalitis are usually known as generalized nonspecific cerebral abnormalities. The aim of this study was to investigate the presence of a special EEG pattern for patients with encephalitis and to explore features related to this special and uncommon pattern. METHODS: EEG monitoring was performed for every patient aged >15 years with encephalitis who was hospitalized between December 2011 and March 2014. Clinical characteristics and EEG recordings were collected and evaluated. RESULTS: Fifty-two patients with encephalitis were enrolled in our study with a 2-h median EEG recording time, and extreme beta brushes (EBBs) occurred in 17 patients (32.7%). Its presence was not significant regarding gender, age, psychiatric medication use, EEG rhythmic disorganization (P > 0.05). Nevertheless, among the patients with EBBs, nine patients (52.9%) had epileptic seizures that had a significant detection rate (P < 0.05); moreover, the cerebrospinal fluid (CSF) or serum of 15 patients (88.2%) with EBBs was positive for antibodies (P < 0.05). Four patients (23.5%) who had EBB had corresponding regional distributions on neuroimaging scans. The EBBs completely correlated with the regional distributions of spike discharges for four patients. CONCLUSION: EBB is a special EEG pattern for patients with encephalitis, especially those with epileptic seizures or who have antibody-positive CSF/serum, and should be considered in clinical practice. PMID- 26365966 TI - Advantage in Bright-blood and Black-blood Magnetic Resonance Imaging with High resolution for Analysis of Carotid Atherosclerotic Plaques. AB - BACKGROUND: About 50% of the cerebral ischemia events are induced by intracranial and extracranial atherosclerosis. This study aimed to evaluate the feasibility and accuracy for displaying atherosclerotic plaques in carotid arteries and analyzing their ingredients by using high-resolution new magnetic resonance imaging (MRI) techniques. METHODS: Totally, 49 patients suspected of extracranial carotid artery stenosis were subjected to cranial MRI scan and magnetic resonance angiography (MRA) examination on carotid arteries, and high-resolution bright blood and black-blood MRI analysis was carried out within 1 week. Digital subtraction angiography (DSA) examination was carried out for 16 patients within 1 month. RESULTS: Totally, 103 plaques were detected in the 49 patients, which were characterized by localized or diffusive thickening of the vessel wall, with the intrusion of crescent-shaped abnormal signal into lumens. Fibrous cap was displayed as isointensity in T1-weighted image (T1WI) and hyperintensities in proton density weighted image (PDWI) and T2-weighted image (T2WI), lipid core was displayed as isointensity or slight hyperintensities in T1WI, isointensity, hyperintensities or hypointensity in PDWI, and hypointensity in T2WI. Calcification in plaques was detected in 11 patients. Eight patients were detected with irregular plaque surface or ulcerative plaques, which were characterized by irregular intravascular space surface in the black-blood sequences, black hypointensity band was not detected in three-dimensional time-of flight, or the hypointensity band was not continuous, and intrusion of hyperintensities into plaques can be detected. Bright-blood and black-blood techniques were highly correlated with the diagnosis of contrast-enhanced MRA in angiostenosis degree, Rs = 0.97, P < 0.001. In comparison to DSA, the sensitivity, specificity, and accuracy of MRI diagnosis of stenosis for >=50% were 88.9%, 100%, and 97.9%, respectively. CONCLUSIONS: High-resolution bright blood and black-blood sequential MRI analysis can accurately analyze ingredients in atherosclerotic plaques. Determined by DSA, MRI diagnosis of stenosis can correctly evaluate the serious degree of arteriostenosis. PMID- 26365967 TI - Calculation of Coronary Angiographic Total Blush in Patients with Coronary Artery Disease and its Prognostic Implication. AB - BACKGROUND: Myocardial perfusion grade (MPG) is an accepted method of evaluating myocardial perfusion. However, it does not take into the account, the extent of the perfusion. We hypothesized that myocardial blush area times MPG (total blush) would be more accurate than simple MPG, and yield better prognostic information. METHODS: About 34 patients were recruited after they had consented to both coronary angiography (CAG) and single photon emission computed tomography (SPECT), and divided into two groups. A special dedicated computer was employed to calculate the total blush. The CAG was performed as a conventional way. Scintigraphic technetium 99m methoxyisobutyl-isonitrile rest and stress images were evaluated quantitatively. The comparison was made between stenosis versus chronic total occlusion (CTO), MPG 1, 2 versus MPG 3, percutaneous intervention (PCI) successful versus failure. A correlation was made between ejection fraction (EF) and myocardial perfusion by MPG, total blush, SPECT, and syntax score. RESULTS: The perfusion indices of total blush, summed difference score (SDS) and syntax score were insignificant between the two groups (P > 0.05). However, the left ventricular end diastolic volume was significantly larger in CTO (P < 0.05). The patients with stenosis had better MPG than with CTO (P < 0.05). The increased MPG was associated with increased total blush, higher syntax score, and EF (P < 0.05). Successful PCI resulted in better perfusion indicated by increased total blush, and MPG (P < 0.05) but successful PCI did not change syntax score, EF and SDS significantly. Multivariate linear analysis with EF as the dependent factor and syntax score, SDS, total blush, blush area, and MPG as the independent factors showed a significantly higher degree of correlation (R = 0.87, P < 0.05). CONCLUSION: After PCI the total blush and EF improved significantly indicating its potential application in the future. PMID- 26365968 TI - Contrast-enhanced Ultrasound in Detecting Endoleaks with Failed Computed Tomography Angiography Diagnosis after Endovascular Abdominal Aortic Aneurysm Repair. AB - BACKGROUND: Endovascular aneurysm repair (EVAR) is one of the first-line therapies of abdominal aortic aneurysms. Postoperative endoleak is the most common complication of EVAR. Computed tomography angiography (CTA), which is routine for follow-up, has side effects (e.g., radiation) and also has a certain percentage of missed diagnosis. Preliminary studies on contrast-enhanced ultrasound (CEUS) have shown that the sensitivity of CEUS for detecting endoleak is no lower than that of CTA. To investigate the advantages of CEUS, we conducted CEUS examinations of post-EVAR cases in which CTA failed to detect endoleak or could not verify the type of endoleak. METHODS: Post-EVAR patients, who were clinically considered to have endoleak and met the inclusion criteria were enrolled between March 2013 and November 2014. All of the patients underwent color Doppler flow imaging (CDFI) and a CEUS examination. Size, location, microbubble dispersion, and hemodynamic characteristics of leaks were recorded. Comparison between the diagnosis of CEUS and CDFI was conducted using Fisher's exact test and clinical outcomes of all patients were followed up. RESULTS: Sixteen patients were enrolled, and 12 (75%) had endoleaks with verified types by CEUS. Among 12 cases of endoleaks were positive by CEUS, 10 were CDFI-positive, and the four CEUS-negative cases were all negative by CDFI. The diagnostic values of CEUS and CDFI were statistically different (P = 0.008). Six patients with high pressure endoleaks received endovascular re-intervention guided by CEUS results. One patient with type III endoleak had open surgery when endovascular repair failed. CONCLUSIONS: CEUS is a new, safe, and effective means for detection of endoleaks post-EVAR. This technique can be used as a supplement for routine CTA follow-up to provide more detailed information on endoleak and its category. PMID- 26365969 TI - Ifosfamide, Cisplatin or Carboplatin, and Etoposide (ICE)-based Chemotherapy for Mobilization of Autologous Peripheral Blood Stem Cells in Patients with Lymphomas. AB - BACKGROUND: High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is a promising approach for lymphomas. This study aimed to evaluate the effect of ifosfamide, cisplatin or carboplatin, and etoposide (ICE) based regimen as a mobilization regimen on relapsed, refractory, or high-risk aggressive lymphoma. METHODS: From June 2001 to May 2013, patients with lymphomas who mobilized by ICE-based regimen for ASCT were analyzed in this retrospective study. The results of the autologous peripheral blood stem cells collection, toxicity, engraftment after ICE-based mobilization regimen were analyzed in this study. Furthermore, risk factors for overall survival (OS) and progression free survival (PFS) were evaluated by univariate analysis. RESULTS: The stem cells were mobilized using ICE-based regimen plus rituximab or ICE-based regimen alone in 12 patients and 54 patients, respectively. The results of stem cell mobilization were excellent. Ninety-seven percentages of the patients had the stem cell collection of at least 2.0 * 10 6 CD34 + cells/kg and 68% had at least 5 * 10 6 CD34 + cells/kg. Fifty-eight percentage of the patients experienced Grade 4 neutropenia, 20% developed febrile neutropenia, and only 12% had Grade 4 thrombocytopenia. At a median follow-up of 63.8 months, the 5-year PFS and OS were 64.4% and 75.3%, respectively. CONCLUSION: ICE is a powerful regimen for stem cell mobilization in patients with lymphomas. PMID- 26365970 TI - Expression of Total Vascular Endothelial Growth Factor and the Anti-angiogenic VEGF 165 b Isoform in the Vitreous of Patients with Retinopathy of Prematurity. AB - BACKGROUND: This study was to examine the expression of total vascular endothelial growth factor (VEGF) and the anti-angiogenic VEGF 165 b isoform in the vitreous body of retinopathy of prematurity (ROP) patients, and to further study the role of the VEGF splicing in the development of ROP. METHODS: This was a prospective clinical laboratory investigation study. All patients enrolled received standard ophthalmic examination with stage 4 ROP that required vitrectomy to collect the vitreous samples. The control samples were from congenital cataract patients. The expression of total VEGF and the anti angiogenic VEGF 165 b were measured by enzyme-linked immunosorbent assay. Results were analyzed statistically using nonparametric tests. RESULTS: The total VEGF level was markedly elevated in ROP samples while VEGF 165 b was markedly decreased compared to control group. The relative protein expression level of VEGF 165 b isoform was significantly decreased in ROP patients which were correlated with the ischemia-induced neovascularization. CONCLUSIONS: There was a switch of VEGF splicing from anti-angiogenic to pro-angiogenic family in ROP patients. A specific inhibitor that more selectively targets VEGF 165 and controls the VEGF splicing between pro- and anti-angiogenic families might be a more effective therapy for ROP. PMID- 26365971 TI - IVS8+1 DelG, a Novel Splice Site Mutation Causing DFNA5 Deafness in a Chinese Family. AB - BACKGROUND: Nonsyndromic hearing loss (NSHL) is highly heterogeneous, in which more than 90 causative genes have currently been identified. DFNA5 is one of the deafness genes that known to cause autosomal dominant NSHL. Until date, only five DFNA5 mutations have been described in eight families worldwide. In this study, we reported the identification of a novel pathogenic mutation causing DFNA5 deafness in a five-generation Chinese family. METHODS: After detailed clinical evaluations of this family, the genomic DNA of three affected individuals was selected for targeted exome sequencing of 101 known deafness genes, as well as mitochondrial DNA and microRNA regions. Co-segregation analysis between the hearing loss and the candidate variant was confirmed in available family members by direct polymerase chain reaction (PCR)-Sanger sequencing. Real-time PCR (RT PCR) was performed to investigate the potential effect of the pathogenic mutation on messenger RNA splicing. RESULTS: Clinical evaluations revealed a similar deafness phenotype in this family to that of previously reported DFNA5 families with autosomal dominant, late-onset hearing loss. Molecular analysis identified a novel splice site mutation in DFNA5 intron 8 (IVS8+1 delG). The mutation segregated with the hearing loss of the family and was absent in 120 unrelated control DNA samples of Chinese origin. RT-PCR showed skipping of exon 8 in the mutant transcript. CONCLUSIONS: We identified a novel DFNA5 mutation IVS8+1 delG in a Chinese family which led to skipping of exon 8. This is the sixth DFNA5 mutation relates to hearing loss and the second one in DFNA5 intron 8. Our findings provide further support to the hypothesis that the DFNA5-associated hearing loss represents a mechanism of gain-of-function. PMID- 26365972 TI - Intraarticular Injection of Allogenic Mesenchymal Stem Cells has a Protective Role for the Osteoarthritis. AB - BACKGROUND: Researchers initially proposed the substitution of apoptotic chondrocytes in the superficial cartilage by injecting mesenchymal stem cells (MSCs) intraarticularly. This effect was termed as bio-resurfacing. Little evidence supporting the treatment of osteoarthritis (OA) by the delivery of a MSC suspension exists. The aim of this study was to investigate the effects of injecting allogenic MSCs intraarticularly in a rat OA model and to evaluate the influence of immobility on the effects of this treatment. METHODS: We established a rat knee OA model after 4 and 6 weeks and cultured primary bone marrow MSCs. A MSC suspension was injected into the articular space once per week for 3 weeks. A subgroup of knee joints was immobilized for 3 days after each injection, while the remaining joints were nonimmobilized. We used toluidine blue staining, Mankin scores, and TdT-mediated dUTP-biotin nick end labeling staining to evaluate the therapeutic effect of the injections. Comparisons between the therapy side and the control side of the knee joint were made using paired t-test, and comparisons between the immobilized and nonimmobilized subgroups were made using the unpaired t-test. A P value < 0.05 was considered significant. RESULTS: The three investigative approaches revealed less degeneration on the therapy sides of the knee joints than the control sides in both the 4- and 6-week groups (P < 0.05), regardless of immobilization. No significant differences were observed between the immobilized and nonimmobilized subgroups (P > 0.05). CONCLUSIONS: Therapy involving the intraarticular injection of allogenic MSCs promoted cartilage repair in a rat arthritis model, and 3-day immobility after injection had little effect on this therapy. PMID- 26365973 TI - Aggressive Blood Pressure Lowing Therapy in Patients with Acute Intracerebral Hemorrhage is Safe: A Systematic Review and Meta-analysis. AB - BACKGROUND: The influence of blood pressure (BP) lowering on intracerebral hemorrhage (ICH) patients is unclear. To assess the safety and efficacy of aggressive antihypertensive therapies in acute ICH patients, we carried out a systematic review and meta-analysis. METHODS: PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, and VIP database up to July 2014 were searched. High-quality randomized controlled trials were included. Low-quality trials were excluded. Serious adverse events were defined as the primary outcome. The secondary outcomes were hematoma enlargement (HE) at 24 h after onset, mortality, and favorable clinical outcome at 90 days. RESULTS: Four high-quality trials involving a total of 1427 patients met the inclusion criteria and were analyzed. Odds ratios (ORs) of primary outcome was 0.96 (95% confidence interval [CI ]: 0.82-1.13, P = 0.61). ORs of HE at 24 h after onset, mortality and favorable clinical outcome at 90 days were 0.91 (95% CI: 0.72-1.17, P = 0.47), 0.97 (95% CI: 0.79-1.20, P = 0.81), 1.13 (95% CI: 0.98-1.30, P = 0.09) respectively. CONCLUSIONS: Aggressive BP management policies are safe and might have a potency of reducing HE and improving clinical outcome. PMID- 26365974 TI - Apolipoprotein J: A New Predictor and Therapeutic Target in Cardiovascular Disease? AB - OBJECTIVE: To review the functional mechanism of apolipoprotein J (apoJ) in the process of atherosclerosis and the feasibility of apoJ as a therapeutic endpoint. DATA SOURCES: Relevant articles published in English from 1983 to present were selected from PubMed. The terms of "atherosclerosis, apolipoprotein J, clusterin (CLU), oxidative stress, and inflammation" were used for searching. STUDY SELECTION: Articles studying the role of apoJ with atherosclerosis and restenosis after injury were reviewed. Articles focusing on the intrinsic determinants of atherosclerosis were selected. The exclusion criteria of articles were that the studies on immunologic vasculitis. RESULTS: ApoJ, involved in numerous physiological process important for lipid transportation and vascular smooth muscle cell differentiation, including apoptotic cell death, cell-cycle regulation, cell adhesion, tissue remodeling, immune system regulation, and oxidative stress, plays a role in the development of clinical atherosclerosis. In the process of relieving atherosclerosis, apoJ can promote cholesterol and phospholipid export from macrophage-foam cells, and exhibit cytoprotective and anti-inflammatory actions by interacting with lots of known inflammatory proteins which may predict the onset of clinical cardiovascular events and may actually play a causal role in mediating atherosclerotic disease such as C-reactive protein, paraoxonase, and leptin. As known as CLU, apoJ has been identified to play central roles in the process of vascular smooth cells migration, adhesion, and proliferation, which can contribute significantly to restenosis after vascular injury. CONCLUSIONS: Intense effort and substantial progress have been made to identify the apoJ that relieves atherosclerosis and vascular restenosis after percutaneous coronary intervention. More work is needed to elucidate the exact mechanisms of and the interrelationship between the actions of apoJ and to successfully achieve regression of atherosclerosis by regarding it as a therapeutic endpoint. PMID- 26365975 TI - Using Plan-Do-Check-Act Circulation to Improve the Management of Panic Value in the Hospital. PMID- 26365976 TI - Prognostic Factors of Wilms' Tumor Complicated with Nephroblastomatosis. PMID- 26365977 TI - Effects of Heart Rate Variability Biofeedback Therapy on Patients with Poststroke Depression: A Case Study. PMID- 26365978 TI - Analysis and Treatment of Multiple Severe Venous Vascular Malformation Syndrome Combined with Coagulopathy. PMID- 26365979 TI - Right Pulmonary Artery to Left Atrial Fistula Confirmed by 320-slice Computerized Tomography. PMID- 26365980 TI - Successful Treatment with Rituximab in a Patient with Castleman's Disease Complicated by Systemic Lupus Erythematosus and Severe Autoimmune Thrombocytopenia. PMID- 26365981 TI - Peripheral Nerve Stimulation for Occipital Neuralgia. PMID- 26365982 TI - Development of Crescentic Immunoglobulin A Nephritis and Multiple Autoantibodies in a Patient during Adalimumab Treatment for Rheumatoid Arthritis. PMID- 26365983 TI - Endoplasmic reticulum chaperone gp96 in macrophages is essential for protective immunity during Gram-negative pneumonia. AB - Klebsiella pneumoniae is among the most common Gram-negative bacteria that cause pneumonia. Gp96 is an endoplasmic reticulum chaperone that is essential for the trafficking and function of Toll-like receptors (TLRs) and integrins. To determine the role of gp96 in myeloid cells in host defence during Klebsiella pneumonia, mice homozygous for the conditional Hsp90b1 allele encoding gp96 were crossed with mice expressing Cre-recombinase under control of the LysM promoter to generate LysMcre-Hsp90b1-flox mice. LysMcre-Hsp90b1-flox mice showed absence of gp96 protein in macrophages and partial depletion in monocytes and granulocytes. This was accompanied by almost complete absence of TLR2 and TLR4 on macrophages. Likewise, integrin subunits CD11b and CD18 were not detectable on macrophages, while being only slightly reduced on monocytes and granulocytes. Gp96-deficient macrophages did not release pro-inflammatory cytokines in response to Klebsiella and displayed reduced phagocytic capacity independent of CD18. LysMcre-Hsp90b1-flox mice were highly vulnerable to lower airway infection induced by K. pneumoniae, as reflected by enhanced bacterial growth and a higher mortality rate. The early inflammatory response in Hsp90b1-flox mice was characterized by strongly impaired recruitment of granulocytes into the lungs, accompanied by attenuated production of pro-inflammatory cytokines, while the inflammatory response during late-stage pneumonia was not dependent on the presence of gp96. Blocking CD18 did not reproduce the impaired host defence of LysMcre-Hsp90b1-flox mice during Klebsiella pneumonia. These data indicate that macrophage gp96 is essential for protective immunity during Gram-negative pneumonia by regulating TLR expression. PMID- 26365985 TI - Associations among pretreatment tumor necrosis and the expression of HIF-1alpha and PD-L1 in advanced oral squamous cell carcinoma and the prognostic impact thereof. AB - OBJECTIVE: The treatment strategies for advanced oral squamous cell carcinoma (OSCC), especially with necrotic changes, are not effective. The programmed death ligand 1 (PD-L1) immune escape may be one of the underlying sources of resistance. Furthermore, anti-PD-L1 directed immunotherapy may be another choice for adjuvant therapy. Therefore, the expression of PD-L1 in advanced OSCC with necrotic changes is very important. MATERIALS AND METHODS: A total of 218 eligible patients with advanced stage (stage III/IV) OSCC and neck metastasis were enrolled. The presence of necrosis was reviewed by pretreatment magnetic resonance imaging. Paired paraffin-embedded primary tumor and metastatic lymph nodes (LN) sections were stained with antibodies against hypoxia-inducible factor 1alpha (HIF-1alpha) and PD-L1. Moderate-to strong HIF-1alpha nuclear staining in >10% and cell surface PD-L1 expression in >5% of OSCC cells were recorded as a positive result. RESULTS: For advanced OSCC with necrotic changes, there was substantial agreement in primary tumor (kappa value 0.54) and almost perfect agreement in metastatic LN (kappa value 0.86) between HIF-1alpha and PD-L1 expression. The patients with both necrosis and positive PD-L1 expression in OSCC surrounding necrosis had worse disease control and survival outcomes. After multivariate analysis, metastatic LN necrosis and positive PD-L1 expression were found to be significant independent adverse factors. CONCLUSION: Advanced OSCC patients with both necrosis and positive PD-L1 expression in OSCC surrounding necrosis had worse outcome. The aggressive behavior of advanced OSCC could be partially related to PD-L1 immune escape. These patients may be good candidates for anti-PD-L1 immunotherapy. PMID- 26365984 TI - IP3R deficit underlies loss of salivary fluid secretion in Sjogren's Syndrome. AB - The autoimmune exocrinopathy, Sjogren's syndrome (SS), is associated with secretory defects in patients, including individuals with mild lymphocytic infiltration and minimal glandular damage. The mechanism(s) underlying the secretory dysfunction is not known. We have used minor salivary gland biopsies from SS patients and healthy individuals to assess acinar cell function in morphologically intact glandular areas. We report that agonist-regulated intracellular Ca(2+) release, critically required for Ca(2+) entry and fluid secretion, is defective in acini from SS patients. Importantly, these acini displayed reduction in IP3R2 and IP3R3, but not AQP5 or STIM1. Similar decreases in IP3R and carbachol (CCh)-stimulated [Ca(2+)]i elevation were detected in acinar cells from lymphotoxin-alpha (LTalpha) transgenic (TG) mice, a model for (SS). Treatment of salivary glands from healthy individuals with LT alpha, a cytokine linked to disease progression in SS and IL14alpha mice, reduced Ca(2+) signaling. Together, our findings reveal novel IP3R deficits in acinar cells that underlie secretory dysfunction in SS patients. PMID- 26365986 TI - MicroRNA-24 induces cisplatin resistance by targeting PTEN in human tongue squamous cell carcinoma. AB - BACKGROUND: miR-24 is one of the most significantly up-regulated miRNAs in tongue squamous cell carcinoma (TSCC). PTEN plays an important role in the cell survival and cisplatin resistance of multiple cancers. However, it remains unclear what role does function and mechanism of miR-24 and PTEN play in TSCC. METHODOLOGY/PRINCIPAL FINDINGS: In this study, miR-24 expression was detected in 79 cases of paired TSCC and normal tissues and 8 TSCC cell lines by real-time PCR and the relevance between miR-24 expression and clinicopathological parameters were analyzed. Further, we demonstrated that deregulation of miR-24 was found to associate with high grade and late stage tumor. In addition, miR-24 induces cell survival and cisplatin resistance through targeting 3'-UTR region of the PTEN, which leads to downregulation of PTEN protein and activation of Akt pro-survival pathway. CONCLUSIONS/SIGNIFICANCE: In conclusion, our results demonstrated that deregulation of miR-24 is a recurrent event in human tongue squamous cell carcinoma and associate with tumor progression and that miR-24 induces cell survival and cisplatin resistance primarily through targeting PTEN/Akt pathway. Thus, miR-24 could be important targets for intervention of this malignancy. PMID- 26365987 TI - On the interfacial fracture resistance of resin-bonded zirconia and glass infiltrated graded zirconia. AB - OBJECTIVE: A major limiting factor for the widespread use of zirconia in prosthetic dentistry is its poor resin-cement bonding capabilities. We show that this deficiency can be overcome by infiltrating the zirconia cementation surface with glass. Current methods for assessing the fracture resistance of resin ceramic bonds are marred by uneven stress distribution at the interface, which may result in erroneous interfacial fracture resistance values. We have applied a wedge-loaded double-cantilever-beam testing approach to accurately measure the interfacial fracture resistance of adhesively bonded zirconia-based restorative materials. METHODS: The interfacial fracture energy GC was determined for adhesively bonded zirconia, graded zirconia and feldspathic ceramic bars. The bonding surfaces were subjected to sandblasting or acid etching treatments. Baseline GC was measured for bonded specimens subjected to 7 days hydration at 37 degrees C. Long-term GC was determined for specimens exposed to 20,000 thermal cycles between 5 and 55 degrees C followed by 2-month aging at 37 degrees C in water. The test data were interpreted with the aid of a 2D finite element fracture analysis. RESULTS: The baseline and long-term GC for graded zirconia was 2-3 and 8 times greater than that for zirconia, respectively. More significantly, both the baseline and long-term GC of graded zirconia were similar to those for feldspathic ceramic. SIGNIFICANCE: The interfacial fracture energy of feldspathic ceramic and graded zirconia was controlled by the fracture energy of the resin cement while that of zirconia by the interface. GC for the graded zirconia was as large as for feldspathic ceramic, making it an attractive material for use in dentistry. PMID- 26365988 TI - Residual micro-stress distributions in heat-pressed ceramic on zirconia and porcelain-fused to metal systems: Analysis by FIB-DIC ring-core method and correlation with fracture toughness. AB - OBJECTIVES: The production of fixed partial dentures (FPDs) induces complex residual stress profiles, due to both the thermal expansion coefficient mismatch between the veneering ceramic and the framework and to the thermal gradients occurring during the final cooling. Detailed knowledge of residual stress distributions in the veneering ceramics is important to understand the interface phenomena with the framework and the consequences of the different firing systems. The first objective of this study was to analyse the residual stress distribution in heat-pressed ceramic on zirconia core with micrometer spatial resolution, with also a focus on the stress at the interface versus porcelain fused-to-metal samples. The second purpose was to correlate the residual stress with the fracture toughness. METHODS: The micron-scale focused ion beam (FIB) ring-core method was used to map the residual stress over the cross-sections of the veneering ceramics. The methodology is based on FIB micro-milling of annular trenches, combined with high-resolution in situ scanning electron microscope (SEM) imaging, a full field strain analysis by digital image correlation (DIC) and numerical models for residual stress calculation. Fracture toughness was evaluated by using high load Vickers indentation and hardness/modulus were measured by nanoindentation testing also across the interfaces. RESULTS: Both prosthetic systems showed a compressive stress at the ceramic surface on a micron scale. The stress profile for porcelain fused to metal (PFM) showed a transition to tensile stress at the half of the layer, whilst the stress in proximity of the interface was more compressive in both the cases. Residual stress on a micron scale are higher in magnitude than the corresponding macro-scale values reported in the literature, due to the stress relaxation given, at larger scales, by micro voids and cracks. The stress field was directly correlated with the indentation fracture toughness, which was higher in those areas where the compressive stress is greater. Stress analysis in correspondence of interfacial porosity for the zirconia sample also showed that micro-defects could induce local modifications of the residual stress field, which may even locally generate a tensile stress state. SIGNIFICANCE: The interfacial stress in dental systems was analysed on a micron scale and can give further insights into the process/property/performance correlation for this class of materials. In particular, interfacial and/or local modifications of the residual stress are expected to have a significant influence on crack nucleation mechanism in correspondence of micro-defects. A direct correlation between residual stress distribution and fracture toughness was proposed. It is noteworthy that the method can be used to study real crowns and bridges. In fact, complex geometries can be easily analysed by this procedure. PMID- 26365990 TI - Separation of Enantiomers of a Phospholipid in Langmuir Monolayers by a New Selector. AB - Chiral discrimination in a racemic mixture of dipalmitoylphosphatidylcholine (DPPC) is induced by a new selector at the water-air interface: L-DPPC is segregated in the condensed phase of a Langmuir monolayer upon interactions with an enantiopure amphiphilic compound. PMID- 26365989 TI - Mediterranean Diet and Invasive Breast Cancer Risk Among Women at High Cardiovascular Risk in the PREDIMED Trial: A Randomized Clinical Trial. AB - IMPORTANCE: Breast cancer is the leading cause of female cancer burden, and its incidence has increased by more than 20% worldwide since 2008. Some observational studies have suggested that the Mediterranean diet may reduce the risk of breast cancer. OBJECTIVE: To evaluate the effect of 2 interventions with Mediterranean diet vs the advice to follow a low-fat diet (control) on breast cancer incidence. DESIGN, SETTING, AND PARTICIPANTS: The PREDIMED study is a 1:1:1 randomized, single-blind, controlled field trial conducted at primary health care centers in Spain. From 2003 to 2009, 4282 women aged 60 to 80 years and at high cardiovascular disease risk were recruited after invitation by their primary care physicians. INTERVENTIONS: Participants were randomly allocated to a Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with mixed nuts, or a control diet (advice to reduce dietary fat). MAIN OUTCOMES AND MEASURES: Breast cancer incidence was a prespecified secondary outcome of the trial for women without a prior history of breast cancer (n = 4152). RESULTS: After a median follow-up of 4.8 years, we identified 35 confirmed incident cases of breast cancer. Observed rates (per 1000 person-years) were 1.1 for the Mediterranean diet with extra-virgin olive oil group, 1.8 for the Mediterranean diet with nuts group, and 2.9 for the control group. The multivariable-adjusted hazard ratios vs the control group were 0.32 (95% CI, 0.13 0.79) for the Mediterranean diet with extra-virgin olive oil group and 0.59 (95% CI, 0.26-1.35) for the Mediterranean diet with nuts group. In analyses with yearly cumulative updated dietary exposures, the hazard ratio for each additional 5% of calories from extra-virgin olive oil was 0.72 (95% CI, 0.57-0.90). CONCLUSIONS AND RELEVANCE: This is the first randomized trial finding an effect of a long-term dietary intervention on breast cancer incidence. Our results suggest a beneficial effect of a Mediterranean diet supplemented with extra virgin olive oil in the primary prevention of breast cancer. These results come from a secondary analysis of a previous trial and are based on few incident cases and, therefore, need to be confirmed in longer-term and larger studies. TRIAL REGISTRATION: ISRCTN.org Identifier: ISRCTN35739639. PMID- 26365991 TI - Acrolein contributes to TRPA1 up-regulation in peripheral and central sensory hypersensitivity following spinal cord injury. AB - Acrolein, an endogenous aldehyde, has been shown to be involved in sensory hypersensitivity after rat spinal cord injury (SCI), for which the pathogenesis is unclear. Acrolein can directly activate a pro-algesic transient receptor protein ankyrin 1 (TRPA1) channel that exists in sensory neurons. Both acrolein and TRPA1 mRNA are elevated post SCI, which contributes to the activation of TRPA1 by acrolein and consequently, neuropathic pain. In the current study, we further showed that, post-SCI elevation of TRPA1 mRNA exists not only in dorsal root ganglias but also in both peripheral (paw skin) and central endings of primary afferent nerves (dorsal horn of spinal cord). This is the first indication that pain signaling can be over-amplified in the peripheral skin by elevated expressions of TRPA1 following SCI, in addition over-amplification previously seen in the spinal cord and dorsal root ganglia. Furthermore, we show that acrolein alone, in the absence of physical trauma, could lead to the elevation of TRPA1 mRNA at various locations when injected to the spinal cord. In addition, post-SCI elevation of TRPA1 mRNA could be mitigated using acrolein scavengers. Both of these attributes support the critical role of acrolein in elevating TRPA1 expression through gene regulation. Taken together, these data indicate that acrolein is likely a critical causal factor in heightening pain sensation post-SCI, through both the direct binding of TRPA1 receptor, and also by boosting the expression of TRPA1. Finally, our data also further support the notion that acrolein scavenging may be an effective therapeutic approach to alleviate neuropathic pain after SCI. We propose that the trauma-mediated elevation of acrolein causes neuropathic pain through at least two mechanisms: acrolein stimulates the production of transient receptor protein ankyrin 1 (TRPA1) in both central and peripheral locations, and it activates TRPA1 channels directly. Therefore, acrolein appears to be a critical factor in the pathogenesis of post-SCI sensory hypersensitivity, becoming a novel therapeutic target to relieve both acute and chronic post-SCI neuropathic pain. PMID- 26365993 TI - The role of EUS and EUS-guided FNA in the management of subepithelial lesions of the esophagus: A large, single-center experience. AB - BACKGROUND: Referral for endosonographic evaluation of subepithelial lesions seen in the gastrointestinal (GI) tract is fairly common. Although rarely studied separately in details, esophageal lesions have some unique differences from other GI sites and might deserve some special considerations regarding follow-up and management. MATERIALS AND METHODS: All cases referred for endoscopic ultrasound (EUS) evaluation of subepithelial esophageal lesions at Bezmialem University Hospital, a tertiary center in Istanbul, Turkey were retrospectively reviewed. Data were collected for patient and lesion characteristics as well as for pathology results and follow-up if available. Lesions were subcategorized according to their size, location, and final diagnosis. RESULTS: A total of 164 EUS examinations were identified. In 22.5% of cases, the lesion could not be identified by EUS. Of the remaining cases, 57.6% had a lesion larger than 1 cm in size. Extramural compression was the diagnosis in 12% and leiomyoma in around 60%. Thirteen patients had follow-up examinations with only two showing an increase in size after 12 months. Sixty-five EUS-guided fine needle aspirations (EUS-guided FNAs) were performed, with around 50% having nondiagnostic samples and 94% of the remaining samples confirming the presumptive diagnosis. CONCLUSIONS: The majority of subepithelial lesions in the esophagus are benign with extremely low malignancy potential. EUS examinations performed for lesions smaller than 2 cm as well as FNAs taken from lesions smaller than 3 cm might have minimal impact on their ultimate management and outcome. More than one FNA pass should be attempted in order to improve the yield. PMID- 26365994 TI - Can We Finish the Revolution? Gender, Work-Family Ideals, and Institutional Constraint. AB - Why has progress toward gender equality in the workplace and at home stalled in recent decades? A growing body of scholarship suggests that persistently gendered workplace norms and policies limit men's and women's ability to create gender egalitarian relationships at home. In this article, we build on and extend prior research by examining the extent to which institutional constraints, including workplace policies, affect young, unmarried men's and women's preferences for their future work-family arrangements. We also examine how these effects vary across levels of education. Drawing on original survey-experimental data, we ask respondents how they would like to structure their future relationships while experimentally manipulating the degree of institutional constraint under which they state their preferences. Two clear patterns emerge. First, as constraints are removed and men and women can opt for an egalitarian relationship, the majority of them choose this option, regardless of gender or education level. Second, women's relationship structure preferences are more malleable to the removal of institutional constraints via supportive work-family policy interventions than are men's. These findings shed light on important questions about the role of institutions in shaping work-family preferences, underscoring the notion that seemingly gender-traditional work-family decisions are largely contingent on the constraints of current workplaces. PMID- 26365992 TI - Nicotine recruits glutamate receptors to postsynaptic sites. AB - Cholinergic neurons project throughout the nervous system and activate nicotinic receptors to modulate synaptic function in ways that shape higher order brain function. The acute effects of nicotinic signaling on long-term synaptic plasticity have been well-characterized. Less well understood is how chronic exposure to low levels of nicotine, such as those encountered by habitual smokers, can alter neural connections to promote addiction and other lasting behavioral effects. We show here that chronic exposure of hippocampal neurons in culture to low levels of nicotine recruits AMPA and NMDA receptors to the cell surface and sequesters them at postsynaptic sites. The receptors include GluA2 containing AMPA receptors, which are responsible for most of the excitatory postsynaptic current mediated by AMPA receptors on the neurons, and include NMDA receptors containing GluN1 and GluN2B subunits. Moreover, we find that the nicotine treatment also increases expression of the presynaptic component synapsin 1 and arranges it in puncta juxtaposed to the additional AMPA and NMDA receptor puncta, suggestive of increases in synaptic contacts. Consistent with increased synaptic input, we find that the nicotine treatment leads to an increase in the excitatory postsynaptic currents mediated by AMPA and NMDA receptors. Further, the increases skew the ratio of excitatory-to-inhibitory input that the cell receives, and this holds both for pyramidal neurons and inhibitory neurons in the hippocampal CA1 region. The GluN2B-containing NMDA receptor redistribution at synapses is associated with a significant increase in GluN2B phosphorylation at Tyr1472, a site known to prevent GluN2B endocytosis. These results suggest that chronic exposure to low levels of nicotine not only alters functional connections but also is likely to change excitability levels across networks. Further, it may increase the propensity for synaptic plasticity, given the increase in synaptic NMDA receptors. PMID- 26365995 TI - Social recognition in paired but not single male prairie voles. AB - Social recognition is an integral component of behavior that underlies many much larger behavioral suites. For example, monogamous pair bonding is relatively meaningless if an individual cannot recall with whom the bond was with. Prairie voles (Microtus ochrogaster) are a socially monogamous rodent, well known for their long-term pair bonds between males and females. Although previous work has shown that bonded males reliably spend more time with their pair-mate over an unfamiliar female, recent work has demonstrated that single male prairie voles do not discriminate between females. This discrepancy raises the important question: do paired males distinguish between non-mate females? We asked whether pair bonding alters the expression of social recognition in male voles by comparing social recognition of single and pair bonded males using the habituation/dishabituation paradigm. We found that pair bonded, but not single male prairie voles exhibit social recognition of (non-mate) females, suggesting a shift in cognitive behavior after pair bond formation. This difference is not due to differences in motivation to engage in social exchanges, as males attempted to contact unfamiliar females at similar levels. Based on these data, we speculate that the stage of life (single or bonded) influences the relevance of attending to social information of same- and opposite-sex conspecifics. PMID- 26365996 TI - Explaining Party Positions on Decentralization. AB - Debates about decentralization raise cultural questions of identity and economic questions of redistribution and efficiency. Therefore the preferences of statewide parties regarding decentralization are related to their positions on the economic and cultural ideological dimensions. A statistical analysis using data from thirty-one countries confirms this: parties on the economic right are more supportive of decentralization than parties on the economic left, while culturally liberal parties favour decentralization more than culturally conservative parties. However, country context - specifically the degree of regional self-rule, the extent of regional economic disparity and the ideology of regionalist parties - determines whether and how decentralization is linked to the two dimensions. These findings have implications for our understanding of the politics of decentralization by showing how ideology, rooted in a specific country context, shapes the 'mindset' of agents responsible for determining the territorial distribution of power. PMID- 26365997 TI - On speeding up stochastic simulations by parallelization of random number generation. AB - This paper adds to the tool kit of stochastic simulations based on a very simple idea. Applicable to both SSA and Tau-leap algorithms, it can notably reduce computational times. Stochastic simulations are based on computing sample paths based on the generation of random numbers with either exactly stipulated distribution functions as in SSA (Gillespie, 1977) or in the method of interval of quiescence (Shah et al., 1977) or distribution functions featuring approximations designed to promote efficiency (as in Tau-leap algorithms (Cao et al., 2006; Tian and Burrage, 2004; Peng et al., 2007; Gillespie, 2001; Ramkrishna et al., 2014) where a leap condition with the parameter epsilon is used). The usual strategy involves sequential computation of a large number of sample paths over a bounded time interval which is covered by a set of discrete time subintervals obtained by random number generation. The strategy here departs from the foregoing by parallelizing the generation of random subintervals for the set of sample paths until all sample paths have been computed for the stated time interval. The advantage of this procedure lies in the fact that the time for initiation of the random number generator has been notably reduced. Many examples are demonstrated from SSA as well as Tau-leap algorithms to establish that the advantage of the approach is much more than conceptual. PMID- 26365998 TI - Dual pH- and Temperature-Responsive Protein Nanoparticles. AB - Multiply responsive protein nanoparticles are interesting for a variety of applications. Herein, we describe the synthesis of a vault nanoparticle that responds to both temperature and pH. Specifically, poly(N-isopropylacrylamide-co acrylic acid) with a pyridyl disulfide end group was prepared by reversible addition-fragmentation chain transfer (RAFT) polymerization. The polymer had a lower critical solution temperature (LCST) of 31.9 degrees C at pH 5, 44.0 degrees C at pH 6 and above 60 degrees C at pH 7. The polymer was conjugated to human major vault protein (hMVP), and the resulting nanoparticle was analyzed by UV-Vis, dynamic light scattering (DLS) and electron microscopy. The data demonstrated that poly(N-isopropylacrylamide-co-acrylic acid)-vault conjugate did not respond to temperatures below 60 degrees C at pH 7, while the nanoparticles reversibly aggregated at pH 6. Furthermore, it was shown that the vault nanoparticle structure remained intact for at least three heat and cooling cycles. Thus, these dually responsive nanoparticles may serve as a platform for drug delivery and other applications. PMID- 26365999 TI - The Prevention of Positioning Injuries during Gynecologic Operations. Guideline of DGGG (S1-Level, AWMF Registry No. 015/077, February 2015). AB - Purpose: Official guideline published and coordinated by the German Society of Gynecology and Obstetrics (DGGG). Positioning injuries after lengthy gynecological procedures are rare, but the associated complications can be potentially serious for patients. Moreover, such injuries often lead to claims of malpractice and negligence requiring detailed medical investigation. To date, there are no binding evidence-based recommendations for the prevention of such injuries. Methods: This S1-guideline is the work of an interdisciplinary group of experts from a range of different professions who were commissioned by DGGG to carry out a systematic literature search of positioning injuries. Members of the participating scientific societies develop a consensus in an informal procedure. Afterwards the directorate of the scientific society approves the consensus. The recommendations cover. PMID- 26366000 TI - Sonographic Assessment of the Umbilical Cord. AB - The umbilical cord (UC) is a vital connection between fetus and placenta. It constitutes a stable connection to the fetomaternal interface, while allowing the fetal mobility that is of great importance for fetal development in general and fetal neuromotor development in particular. This combination of mechanical stability and flexibility is due to the architecture of the UC. There is however a range of umbilical cord complications that may be life threatening to the fetus and these too can be explained to a large extent by the cord's structural characteristics. This review article discusses clinically relevant aspects of UC ultrasound. PMID- 26366001 TI - Factors for Preterm Births in Germany - An Analysis of Representative German Data (KiGGS). AB - Introduction: Preterm birth is a global scourge, the leading cause of perinatal mortality and morbidity. This study set out to identify the principal risk factors for preterm birth, based on the German Health Interview and Examination Survey for Children and Adolescents (KiGGS). A range of possible factors influencing preterm birth were selected for inclusion in the questionnaire, covering factors such as gender, national origin, immigrant background, demography, living standard, family structure, parental education and vocational training. Methods: All data were taken from the aforementioned KiGGS survey conducted between 2003 and 2006. A total of 17 641 children and adolescents (8656 girls and 8985 boys) drawn from 167 German towns and municipalities deemed to be representative of the Federal Republic of Germany were included in the study. Gestational age at birth was available for 14 234 datasets. The questionnaire included questions from the following areas as possible factors influencing preterm birth: gender, national origins, immigrant background, demography, living standard, family structure, parental education and vocational training. Results: The preterm birth rate was 11.6 %, higher than that of other national statistical evaluations. Around 57.4 % of multiple pregnancies and 10 % of singleton pregnancies resulted in preterm delivery. Multiple pregnancy was found to be the most important risk factor (OR 13.116). With regard to national origins and immigration background, mothers from Turkey, the Middle East, and North Africa had a higher incidence of preterm birth. Preterm birth was more prevalent in cities and large towns than in small towns and villages. Conclusion: Risk factors associated with preterm birth were identified. These should help with the early identification of pregnant women at risk. The preterm birth rate in our survey was higher than that found in other national statistical evaluations based on process data. More than half of all multiple pregnancies ended in preterm birth. PMID- 26366002 TI - Pregnancy and Obstetrical Outcomes in Women Over 40 Years of Age. AB - Introduction: Delayed childbearing is increasing, and advanced maternal age has been associated with an increased risk of obstetrical complications. The purpose of this study was to evaluate pregnancy outcomes in women with advanced maternal age (>= 40 years). Methods: Maternal and obstetrical data were collected from the Department of Obstetrics and Gynecology of the University of Wuerzburg for the period from 2006 to 2011. In this retrospective analysis we compared the outcomes for women aged >= 40 years (n = 405) with those of three younger subgroups (I: < 30 y; II: 30-34 y; III: 35-39 y). Results: Pregnant women older than 40 years had more chronic diseases such as hypertension, needed medical treatment more frequently and had a higher thrombosis risk. Pregnancy-induced diseases such as gestational diabetes, preeclampsia and pregnancy-associated hypertension occurred more often in women >= 40 years of age. Compared to mothers who were younger than 30 years, primiparous women >= 40 years had a more than four times higher overall cesarean section rate and four times higher elective cesarean section rate. Furthermore, they required longer hospital stays, both after cesarean section and after vaginal delivery. The preterm birth rate (<= 32 weeks of gestation) was similar across the different age groups. Conclusions: The outcomes of pregnancy and childbirth and for newborns born to women >= 40 years did not vary significantly from those of younger women if the following conditions were met: a) pre-existing chronic diseases were treated medically and dietetically; b) pregnancy-induced morbidity was monitored regularly and controlled medically; c) women attended regular prenatal check-ups; d) a healthy lifestyle was adhered to during pregnancy, and e) delivery occurred in a perinatal center. PMID- 26366003 TI - Laparoscopic Cerclage as a Treatment Option for Cervical Insufficiency. AB - Background: The traditional surgical treatment for cervical insufficiency is vaginal placement of a cervical cerclage. However, in a small number of cases a vaginal approach is not possible. A transabdominal approach can become an option for these patients. Laparoscopic cervical cerclage is associated with good pregnancy outcomes but comes at the cost of a higher risk of serious surgical complications. The aim of the present study was to evaluate intraoperative and long-term pregnancy outcomes after laparoscopic cervical cerclage, performed either as an interval procedure or during early pregnancy, using a new device with a blunt grasper and a flexible tip. Methods: All women who underwent laparoscopic cervical cerclage for cervical insufficiency in our institution using the Goldfinger(r) device (Ethicon Endo Surgery, Somerville, NJ, USA) between January 2008 and March 2014 were included in the study. Data were collected from the patients' medical records and included complications during and after the above-described procedure. Results: Eighteen women were included in the study. Of these, six were pregnant at the time of laparoscopic cervical cerclage. Mean duration of surgery was 55 +/- 10 minutes. No serious intraoperative or postoperative complications occurred. All patients were discharged at 2.6 +/- 0.9 days after surgery. One pregnancy ended in a miscarriage at 12 weeks of gestation. All other pregnancies ended at term (> 37 weeks of gestation) with good perinatal and maternal outcomes. Summary: Performing a laparoscopic cervical cerclage using a blunt grasper device with a flexible tip does not increase intraoperative complications, particularly in early pregnancy. We believe that use of this device, which is characterized by increased maneuverability, could be an important option to avoid intraoperative complications if surgical access is limited due to the anatomical situation. However, because of the small sample size, further studies are needed to confirm our findings. PMID- 26366004 TI - Placenta Accreta and Total Placenta Previa in the 19th Week of Pregnancy. AB - Placentation disorders are the result of impaired embedding of the placenta in the endometrium. The prevalence of these disorders is estimated to be around 0.3 %. A history of previous prior uterine surgery (especially cesarean section and curettage) is the most common risk factor. Impaired placentation is differentiated into deep placental attachment; marginal, partial and total placenta previa; and placenta accreta, increta and percreta. Treatment depends on the severity of presentation and ranges from expectant management to emergency hysterectomy. In most cases, preterm termination of pregnancy is necessary. We report here on the case of a 39-year-old woman with placenta accreta and total placenta previa who underwent hysterectomy in the 19th week of pregnancy. PMID- 26366005 TI - Acute Fatty Liver of Pregnancy and its Differentiation from Other Liver Diseases in Pregnancy. AB - Background: There are a number of threatening liver diseases that occur during pregnancy. Acute fatty liver of pregnancy is a rare disease associated with high maternal and foetal mortality. Case Report: We report on a young gravida 1 woman who presented to our level 1 perinatal centre in the 36 + 5 week of pregnancy with an isolated elevation of transaminases together with diffuse upper abdominal complaints. After comprehensive diagnostic work-up we performed an emergency delivery by Caesarean section. This was followed by interdisciplinary management. Discussion: The differentiation from other liver diseases seems not to be obvious in all cases. Here we consider the following differential diagnoses: hyperemesis gravidarum, intrahepatic gestational cholestasis, preeclampsia, HELLP syndrome. Conclusion: Rapid diagnosis and delivery as well as interdisciplinary aftercare are necessary in order to reduce maternal and foetal mortality. PMID- 26366006 TI - TEN RILLINGTON PLACE AND THE CHANGING POLITICS OF ABORTION IN MODERN BRITAIN. AB - This article addresses the social, cultural, and political history of backstreet abortion in post-war Britain, focusing on the murders of Beryl Evans and her daughter Geraldine, at Ten Rillington Place in 1949. It shows how the commonplace connection of John Christie to abortion and Beryl Evan's death was not a given in the wider public, legal, political, and forensic imagination of the time, reflecting the multi-layered and shifting meanings of abortion from the date of the original trials in the late 1940s and 1950s, through the subsequent judicial and literary reinvestigations of the case in the 1960s, to its cinematic interpretation in the 1970s. Exploring the language of abortion used in these different contexts, the article reveals changes in the gendering of abortionists, the increasing power and presence of abortion activists and other social reformers, the changing representation of working-class women and men, and the increasing critique of the practice of backstreet abortion. The case is also made for a kind of societal blind spot on abortion at the time of both the Evans and Christie trials; in particular, a reluctance to come to terms with the concept of the male abortionist, which distorted the criminal investigations and the trials themselves. Only when public acceptance for legalizing abortion grew in the more liberal climate of the 1960s and beyond did a revisionist understanding of the murder of Beryl Evans, in which abortion came to be positioned as a central element, gain a sustained hearing. PMID- 26366007 TI - Mixed and Complex Mixed Migration during Armed Conflict: Multidimensional Empirical Evidence from Nepal. AB - Historically, legal, policy, and academic communities largely ascribed to a dichotomy between forced and voluntary migration, creating a black and white vision that was convenient for legal and policy purposes. More recently, discussions have begun addressing the possibility of mixed migration, acknowledging that there is likely a wide continuum between forced and voluntary, and most migrants likely move with some amount of compulsion and some volition, even during armed conflict. While the mixed migration hypothesis is well received, empirical evidence is disparate and somewhat blunt at this point. In this article, I contribute a direct theoretical and causal pathway discussion of mixed migration. I also propose the complex mixed migration hypothesis, which argues that not only do non-conflict related factors influence migration during conflict, but they do so differently than during periods of relative peace. I empirically test both hypotheses in the context of the recent armed conflict in Nepal. Using detailed survey data and event history models, results provide strong evidence for both mixed migration and complex mixed migration during conflict hypotheses. These hypotheses and evidence suggest that armed conflict might have substantial impacts on long-term population growth and change, with significant relevance in both academic and policy spheres. PMID- 26366008 TI - Americocentrism and Art of the Caribbean: Contours of a Time-Space Logic. AB - Art of the transnational Caribbean has come to be positioned by an understanding of the African diaspora that is oriented to an American "centre," a situation to be explored for what it reveals about the hegemonic status of the United States in the discipline of contemporary art history. The predominant uses of the diaspora concept both in art-historical narratives and in curatorial spaces are those that connect to United States-based realities, with little pertinence to a strictly transnational theorization. This has implications for how modern art and contemporary art are thought about in relation to the Caribbean and its diaspora, in a way that this article demonstrates with attention to a number of artists at multiple sites, in Trinidad, Guyana, Britain and America. PMID- 26366009 TI - Do Children's Executive Functions Account for Associations Between Early Autonomy Supportive Parenting and Achievement Through High School? AB - This study evaluated whether the positive association between early autonomy supportive parenting and children's subsequent achievement is mediated by children's executive functions. Using observations of mothers' parenting from the NICHD Study of Early Child Care and Youth Development (N = 1,306), analyses revealed that mothers' autonomy support over the first 3 years of life predicted enhanced executive functions (i.e., inhibition, delay of gratification, and sustained attention) during the year prior to kindergarten and academic achievement in elementary and high school even when mothers' warmth and cognitive stimulation, as well as other factors (e.g., children's early general cognitive skills and mothers' educational attainment) were covaried. Mediation analyses demonstrated that over and above other attributes (e.g., temperament), children's executive functions partially accounted for the association between early autonomy-supportive parenting and children's subsequent achievement. PMID- 26366010 TI - Differences in Expressivity Based on Attractiveness: Target or Perceiver Effects? AB - A significant association exists between adults' expressivity and facial attractiveness, but it is unclear whether the association is linear or significant only at the extremes of attractiveness. It is also unclear whether attractive persons actually display more positive expressivity than unattractive persons (target effects) or whether high and low attractiveness influences expressivity valence judgments (perceiver effects). Experiment 1 demonstrated adult ratings of attractiveness were predictive of expressivity valence only for high and low attractive females and medium attractive males. Experiment 2 showed that low attractive females actually display more negative expressivity than medium and high attractive females, but there were no target effects for males. Also, attractiveness influenced expressivity valence judgments (perceiver effects) for both females and males. Our findings demonstrate that low attractive females are at a particular disadvantage during social interactions due to their low attractiveness, actual displays of negative expressivity, and perceptions of their negative expressivity. PMID- 26366011 TI - Plant protein and secondary metabolites influence diet selection in a mammalian specialist herbivore. AB - For herbivores, nutrient intake is limited by the relatively low nutritional quality of plants and high concentrations of potentially toxic defensive compounds (plant secondary metabolites, PSMs) produced by many plants. In response to phytochemical challenges, some herbivores selectively forage on plants with higher nutrient and lower PSM concentrations relative to other plants. Pygmy rabbits (Brachylagus idahoensis) are dietary specialists that feed on sagebrush (Artemisia spp.) and forage on specific plants more than others within a foraging patch. We predicted that the plants with evidence of heavy foraging (browsed plants) would be of higher dietary quality than plants that were not browsed (unbrowsed). We used model selection to determine which phytochemical variables best explained the difference between browsed and unbrowsed plants. Higher crude protein increased the odds that plants would be browsed by pygmy rabbits and the opposite was the case for certain PSMs. Additionally, because pygmy rabbits can occupy foraging patches (burrows) for consecutive years, their browsing may influence the nutritional and PSM constituents of plants at the burrows. In a post hoc analysis, we did not find a significant relationship between phytochemical concentrations, browse status and burrow occupancy length. We concluded that pygmy rabbits use nutritional and chemical cues while making foraging decisions. PMID- 26366012 TI - A FLEXIBLE PARAMETERIZATION FOR BASELINE MEAN DEGREE IN MULTIPLE-NETWORK ERGMS. AB - The conventional exponential family random graph model (ERGM) parameterization leads to a baseline density that is constant in graph order (i.e., number of nodes); this is potentially problematic when modeling multiple networks of varying order. Prior work has suggested a simple alternative that results in constant expected mean degree. Here, we extend this approach by suggesting another alternative parameterization that allows for flexible modeling of scenarios in which baseline expected degree scales as an arbitrary power of order. This parameterization is easily implemented by the inclusion of an edge count/log order statistic along with the traditional edge count statistic in the model specification. PMID- 26366013 TI - Beyond Preparation: Identity, Cultural Capital, and Readiness for Graduate School in the Biomedical Sciences. AB - In this study, we conducted in-depth interviews with 52 college graduates as they entered a Postbaccalaureate Research Education Program (PREP). Our goal was to investigate what it means for these aspiring scientists, most of whom are from groups underrepresented in the sciences, to feel ready to apply to a doctoral program in the biomedical sciences. For our analysis, we developed and used a theoretical framework which integrates concepts from identity-in-practice literature with Bourdieu's formulation of cultural capital and also examined the impact of racial, ethnic, and gender identities on education and career trajectories. Five patterns of identity work for expected engagement with PREP grew out of our analysis: Credential Seekers, PI Aspirants, Path Builders, Discipline Changers, and Interest Testers. These patterns illuminate differences in perceptions of doing, being, and becoming within science; external and internal foci of identity work; and expectations for institutional and embodied cultural capital. Our findings show that preparing for graduate education is more complex than acquiring a set of credentials as it is infused with identity work which facilitates readiness beyond preparation. This deeper understanding of individual agency and perceptions allows us to shift the focus away from a deficit model where institutions and programs attempt to "fix" students, and to offer implications for programs designed to support college graduates aspiring to become scientists. PMID- 26366015 TI - Interaction of Almost-Collinear Longitudinal Phonons. AB - The interaction of two longitudinal ultrasonic waves to produce sum- and difference-frequency waves has been studied experimentally and theoretically. These interactions are closely analogous to the type of three-phonon interactions believed to be important in low-temperature ultrasonic attenuation. We have applied the coherent-state formalism to a description of these interactions and have discussed the similarities between coherent and incoherent processes. Experimentally we have measured the amplitude of the generated sum- or difference frequency wave as a function of the angle between the input waves and of the amplitude and frequency of the input waves. The effect of crystalline anisotropy has also been observed. The change in amplitude of one of the input waves has been measured as a function of the parameters listed above. In all cases the experimental observations are in good agreement with theory. PMID- 26366014 TI - 2-Allylaminothiazole and 2-allylaminodihydrothiazole derivatives: synthesis, characterization, and evaluation of bioactivity. AB - ABSTRACT: Some reactions of selected chlorooxoesters and haloesters with a 1 allylthiourea under various conditions have been performed. The reactions have been performed in methanol in alkaline and neutral environment. Condensation of 1 allylthiourea with chlorooxoesters has been further led via acetal as intermediate compound. As a result, the compounds containing thiazole and a 4,5 dihydrothiazole ring with a good yield have been obtained. The structures of the compounds were verified by 1H NMR, 13C NMR as well as X-ray diffraction analysis. Due to the potential biological activity of the synthesized compounds, the parameters of their bioavailability have been determined, and the probability of pharmacological action has been defined. All of the obtained compounds fulfilled the rule of five, which indicate their good absorption after oral intake. The probability of pharmacological action and potential targets calculated for the obtained compounds show that they can be potential drugs. GRAPHICAL ABSTRACT: PMID- 26366016 TI - Medical comforts during the heroic age of Antarctic exploration. AB - In the literature of the exploration of the Antarctic in the early 20th century, there are many references to 'medical comforts'. While 'medical comforts' was sometimes used as a euphemism for alcoholic beverages, the term, which originated in the army, covered all foods and drinks used for the treatment and prevention of illness and during convalescence. This article describes the use of medical comforts during the Antarctic expeditions of the so called 'heroic age'. Apart from alcohol, medical comforts included beef extracts, milk extracts and arrowroot. These products were extensively advertised to the medical and nursing professions and to the general public and the Antarctic connection was sometimes used in the advertising. The products were largely devoid of vitamins and their use may have contributed to some of the disease that occurred on these expeditions. PMID- 26366017 TI - Expedient one-pot synthesis of indolo[3,2-c]isoquinolines via a base-promoted N alkylation/tandem cyclization. AB - A transition metal-free, one-pot protocol has been developed for the synthesis of 11H-indolo[3,2-c]isoquinolin-5-amines via the atom economical annulation of ethyl (2-cyanophenyl)carbamates and 2-cyanobenzyl bromides. This method proceeds via sequential N-alkylation and base-promoted cyclization. Optimization data, substrate scope, mechanistic insights, and photoluminescence properties are discussed. PMID- 26366018 TI - Not Your Mother's Suburb: Remaking Communities for a More Diverse Population. AB - The United States is a suburban nation with a majority of Americans living and working in this landscape. But the suburb is more than a physical location; it is also a social production. Built upon a middle class, white, nuclear family ideal, the suburb is now diversifying demographically and economically, yet zoning ordinances and the built environment continue to reflect this outdated ideal. Today's suburb is not your mother's suburb. We argue that these demographic changes create both a point of rupture that challenges traditional land use regulations and actual uses of space, and an opening for communities to embrace and plan for new residents. In order to respond to the needs of a diversifying suburban population, communities need to challenge the underlying assumptions of traditional zoning ordinances - the separation of uses and preference for single family housing. We present an agenda for the future that includes planning responses that rethink the zoning hierarchy, promote new forms of densification, move beyond restrictive family definitions, and experiment with new forms of service delivery. PMID- 26366019 TI - Impregnation of Scots pine and beech with tannin solutions: effect of viscosity and wood anatomy in wood infiltration. AB - The impregnation process of Scots pine and beech samples with tannin solutions was investigated. The two materials involved in the process (impregnation solution and wood samples) are studied in depth. Viscosity of mimosa tannin solutions and the anatomical aspect of beech and Scots pine were analysed and correlated. The viscosity of tannin solutions presents a non-newtonian behaviour when its pH level increases, and in the case of addition of hexamine as a hardener, the crosslinking of the flavonoids turns out to be of great importance. During the impregnation of Scots pine (Pinus sylvestris L.) and beech (Fagus sylvatica L.), the liquid and solid uptakes were monitored while taking into consideration the different conditions of the impregnation process. This method allowed to identify the best conditions needed in order to get a successful preservative uptake for each wooden substrate. The penetration mechanism within the wood of both species was revealed with the aid of a microscopic analysis. Scots pine is impregnated through the tracheids in the longitudinal direction and through parenchyma rays in the radial direction, whereas in beech, the penetration occurs almost completely through longitudinal vessels. PMID- 26366020 TI - Revisiting Pneumatic Nail Gun Trigger Recommendations. AB - Use of a pneumatic nail gun with a sequential actuation trigger (SAT) significantly diminishes the risk for acute traumatic injury compared to use of a contact actuation trigger (CAT) nail gun. A theoretically-based increased risk of work-related musculoskeletal disorders from use of a SAT nail gun, relative to CAT, appears unlikely and remains unproven. Based on current knowledge, the use of CAT nail guns cannot be justified as a safe alternative to SAT nail guns. This letter provides a perspective of ergonomists and occupational safety researchers recommending the use of the sequential actuation trigger for all nail gun tasks in the construction industry. PMID- 26366021 TI - Preliminary Evidence for the Enhancement of Self-Conducted Exposures for OCD using Cognitive Bias Modification. AB - Exposure and Response Prevention (ERP) is the most effective treatment for OCD but it is not accessible to most patients. Attempts to increase the accessibility of ERP via self-directed ERP (sERP) programs such as computerized delivery and bibliotherapy have met with noncompliance, presumably because patients find the exposure exercises unacceptable. Previous research suggests that Cognitive Bias Modification (CBM) interventions may help individuals approach feared situations. The goal of the current study was to test the efficacy of a treatment program for OCD that integrates sERP with CBM. Twenty-two individuals meeting diagnostic criteria for OCD enrolled in our 7-week treatment program. Results suggest that sERP with CBM led to significant reduction of OCD symptoms and functional impairment. Indeed, the magnitude of the effect of this novel treatment, that requires only an initial session with a clinician trained in ERP for OCD, was comparable to that of the gold standard clinician-administered ERP. Moreover, preliminary evidence suggests that CBM interventions targeting interpretation bias may be most effective, whereas those targeting attention and working memory bias may not be so. PMID- 26366022 TI - Contextual Influences on Distress Intolerance: Priming Effects on Behavioral Persistence. AB - Distress intolerance (DI), the inability to tolerate stressful experiences, has been linked to multiple psychiatric conditions and maladaptive coping patterns. Although DI is often considered a trait-like variable, evidence indicates that self-report and behavioral indices of DI can be manipulated by contextual factors. Understanding such contextual influences is important given evidence of unexpected variability in these presumed trait-like measures over brief intervals. The current study examined the influence of context (manipulated by priming concepts of "Interminability" and "Brevity") in predicting behavioral persistence, in relation to self-reported DI. Results indicated that priming Brevity was associated with terminating a cold-pressor task more quickly. Self reported DI was linked to earlier termination, but there was no interaction between self-reported DI and priming condition. Results indicate that contextual cues modulate performance on behavioral measures of DI. Hence, models of DI should consider both trait-like and contextual factors in understanding variability in DI measures. PMID- 26366023 TI - As(III) S-adenosylmethionine methyltransferases and other arsenic binding proteins. AB - Efflux is by far the most common means of arsenic detoxification is by methylation catalyzed by a family of As(III) S-adenosylmethionine (SAM) methyltransferases (MTs) enzymes designated ArsM in microbes or AS3MT in higher eukaryotes. The protein sequence of more than 5000 AS3MT/ArsM orthologues have been deposited in the NCBI database, mostly in prokaryotic and eukaryotic microbes. As(III) SAM MTs are members of a large superfamily of MTs involved in numerous physiological functions. ArsMs detoxify arsenic by conversion of inorganic trivalent arsenic (As(III)) into mono-, di- and trimethylated species that may be more toxic and carcinogenic than inorganic arsenic. The pathway of methylation remains controversial. Several hypotheses will be examined in this review. PMID- 26366024 TI - MR Elastography of Liver Disease: State of the Art. PMID- 26366025 TI - Analysis of Sequence Data Under Multivariate Trait-Dependent Sampling. AB - High-throughput DNA sequencing allows for the genotyping of common and rare variants for genetic association studies. At the present time and for the foreseeable future, it is not economically feasible to sequence all individuals in a large cohort. A cost-effective strategy is to sequence those individuals with extreme values of a quantitative trait. We consider the design under which the sampling depends on multiple quantitative traits. Under such trait-dependent sampling, standard linear regression analysis can result in bias of parameter estimation, inflation of type I error, and loss of power. We construct a likelihood function that properly reflects the sampling mechanism and utilizes all available data. We implement a computationally efficient EM algorithm and establish the theoretical properties of the resulting maximum likelihood estimators. Our methods can be used to perform separate inference on each trait or simultaneous inference on multiple traits. We pay special attention to gene level association tests for rare variants. We demonstrate the superiority of the proposed methods over standard linear regression through extensive simulation studies. We provide applications to the Cohorts for Heart and Aging Research in Genomic Epidemiology Targeted Sequencing Study and the National Heart, Lung, and Blood Institute Exome Sequencing Project. PMID- 26366026 TI - Bayesian Dose-Finding in Two Treatment Cycles Based on the Joint Utility of Efficacy and Toxicity. AB - A phase I/II clinical trial design is proposed for adaptively and dynamically optimizing each patient's dose in each of two cycles of therapy based on the joint binary efficacy and toxicity outcomes in each cycle. A dose-outcome model is assumed that includes a Bayesian hierarchical latent variable structure to induce association among the outcomes and also facilitate posterior computation. Doses are chosen in each cycle based on posteriors of a model-based objective function, similar to a reinforcement learning or Q-learning function, defined in terms of numerical utilities of the joint outcomes in each cycle. For each patient, the procedure outputs a sequence of two actions, one for each cycle, with each action being the decision to either treat the patient at a chosen dose or not to treat. The cycle 2 action depends on the individual patient's cycle 1 dose and outcomes. In addition, decisions are based on posterior inference using other patients' data, and therefore the proposed method is adaptive both within and between patients. A simulation study of the method is presented, including comparison to two-cycle extensions of the conventional 3+3 algorithm, continual reassessment method, and a Bayesian model-based design, and evaluation of robustness. PMID- 26366028 TI - A compact 7-cell Si-drift detector module for high-count rate X-ray spectroscopy. AB - A new Si-drift detector module for fast X-ray spectroscopy experiments was developed and realized. The Peltier-cooled module comprises a sensor with 7 * 7 mm2 active area, an integrated circuit for amplification, shaping and detection, storage, and derandomized readout of signal pulses in parallel, and amplifiers for line driving. The compactness and hexagonal shape of the module with a wrench size of 16mm allow very short distances to the specimen and multi-module arrangements. The power dissipation is 186mW. At a shaper peaking time of 190 ns and an integration time of 450 ns an electronic rms noise of ~11 electrons was achieved. When operated at 7 degrees C, FWHM line widths around 260 and 460 eV (Cu-Kalpha) were obtained at low rates and at sum-count rates of 1.7 MHz, respectively. The peak shift is below 1% for a broad range of count rates. At 1.7 MHz sum-count rate the throughput loss amounts to 30%. PMID- 26366027 TI - The development of hippocampal-dependent memory functions: Theoretical comments on Jabes and Nelson review (2015). AB - Studies investigating the development of memory processes and their neural substrates have flourished over the last two decades. The review by Jabes and Nelson (2015) adds an important piece to our understanding of the maturation of different elements and circuits within the hippocampal system and their association with the progressive development of hippocampal-dependent memory processes in humans. In this accompanying commentary, we explore some additional connections between the nonhuman primate work and the human data, and take the opportunity to highlight some common and additional interpretations of the results. This commentary makes three points: (1) the recognition processes present in the first few days of life may be linked to the early maturation of the medial temporal cortical areas instead of, or in addition to, the early maturation of the subiculum; (2) recent findings on the differential protracted maturation of spatial relational memory processes in monkeys further support the notion proposed by Jabes and Nelson that this protracted development may reflect progressive maturation of the CA1 field of the hippocampus followed by further maturation of CA3/dentate gyrus; (3) finally, further considerations of the differential maturation of the longitudinal hippocampal axis and of the diencephalon are proposed as additional contributors to the refinement of episodic memory functions during development. PMID- 26366029 TI - Genetic and experiential influences on behavior: Twins reunited at seventy-eight years. AB - Twins living in different countries offer opportunities to explore associations between observed differences and experiential effects. This report compared the life histories, cognitive abilities, personality traits, psychomotor skills, medical characteristics, job satisfaction, social support and social relations of dizygotic (DZ) female twins reunited at 78, the world's longest separated set. The twins' advanced age also enabled a study of how co-twin differences in aging may be associated with current behavioral and social differences. Consistent with previous studies, these dizygotic reared apart (DZA) twins showed discordance across some, but not all, traits. Their different rearing situations and life histories may explain current differences in their responses to meeting their twin. This case highlights the importance of both genetic and rearing factors on behavior, but does not allow firm conclusions regarding the extent to which these sources explain individual developmental differences. However, such data contribute to the growing number of cross-culturally separated twins, generating novel hypotheses that may be assessed using larger samples. PMID- 26366030 TI - Genetic and environmental influences on applied creativity: A reared-apart twin study. AB - Applied creativity involves bringing innovation to real-life activities. The first reared-apart twin study assessing genetic and environmental origins of applied creativity, via Draw-a-House (DAH) and Draw-a-Person (DAP) tasks, is presented. Participants included 69 MZA and 53 DZA twin pairs from the Minnesota Study of Twins Reared Apart. Drawings were evaluated by four artists and four non artists. Genetic effects were demonstrated for the DAP (.38-.47), but not for the DAH. Creative personality showed genetic effects (.50), and modest, but significant correlations with scores on the two drawings (rs = .17-.26). Both genetic and nonshared environmental influences underlie variance in applied creativity. Individuals concerned with enhancing creativity among students and others may better understand individual differences in performance and training. PMID- 26366031 TI - Results of a European interlaboratory comparison on gross alpha/beta activity determination in drinking water. AB - An interlaboratory comparison was organised by JRC-IRMM among environmental radioactivity monitoring laboratories for the determination of gross alpha/beta activity concentration in drinking water. Independent standard methods were used for the reference value determination. The performance of participating laboratories was evaluated with respect to the reference values using relative deviations. Sample preparation and measurement methods used by the participating laboratories are detailed, in particular in the view of method-dependency of the results. Many of the participants' results deviate by more than two orders of magnitude from the reference values regardless of the techniques used. This suggests that gross methods need revision. PMID- 26366032 TI - Fast ion chromatography-ICP-QQQ for arsenic speciation. AB - Two methods for the fast separation of arsenic species are presented. The general approach is to modify existing methodology utilizing carbonate eluents for a small particle size, short column length Hamilton PRPX100 column which is interfaced with the Agilent 8800 ICP-QQQ using oxygen as reaction gas and detection of AsO at m/z 91. Using H2O2 in the extractant to oxidize As(III) to As(V) it is possible to separate arsenobetaine from DMA, MMA and As(V) in 1.5 minutes. Such a method may be useful where a measure of total inorganic As is sufficient, for example for regulatory compliance in food or beverage testing. It is possible to separate six As species. i.e the four above and arsenocholine and As(III) in 4.5 minutes using a gradient separation. Such a method could be useful analysis of urinary arsenic species. Coupling with high sensitivity of ICP-QQQ yields equivalent or better detection limits than conventional methods with run times up to 5 times faster, which is a significant benefit for sample throughput and method development. PMID- 26366033 TI - An evaluation on the level of retinoids in the bovine pineal body. AB - Using high performance liquid chromatography, the level of retinoids was determined in the bovine pineal gland, retina, retinal pigment epithelium, cortical and subcortical brain tissues, skeletal muscle and the liver. Similar to the retina, the bovine pineal gland possesses levels of retinol and retinyl esters significantly higher than other brain tissues and muscle. These results are in agreement with the suggestion that the mammalian pineal gland and the retina may be of similar phylogenetic origin. However, unlike the retina, the bovine pineal gland does not possess any detectable level of retinal, the chromophore for visual pigments in the retina. This finding suggests that the bovine pineal gland does not possess rhodopsin nor the property of phototransduction which has been fully established in the retina and pineal glands of lower vertebrates. PMID- 26366034 TI - The Influence of Testing Prompt and Condition on Middle School Students' Retell Performance. AB - This study examined whether the type of prompt or the method of passage reading had an effect on the retell performance of 6th-8th graders randomly assigned to one of four retell testing conditions. Both the type of prompt and the use of follow-up prompting were significantly related to the percentage of predetermined idea units retold. Effect sizes were approximately moderate (d = .44-.62) when one change was made to the prompt but were strong (d = .96-1.05) with a combination of changes. The addition of silent reading did not significantly improve performance. PMID- 26366035 TI - Photoacoustic Characterization of Radiofrequency Ablation Lesions. AB - Radiofrequency ablation (RFA) procedures are used to destroy abnormal electrical pathways in the heart that can cause cardiac arrhythmias. Current methods relying on fluoroscopy, echocardiography and electrical conduction mapping are unable to accurately assess ablation lesion size. In an effort to better visualize RFA lesions, photoacoustic (PA) and ultrasonic (US) imaging were utilized to obtain co-registered images of ablated porcine cardiac tissue. The left ventricular free wall of fresh (i.e., never frozen) porcine hearts was harvested within 24 hours of the animals' sacrifice. A THERMOCOOL (r) Ablation System (Biosense Webster, Inc.) operating at 40 W for 30-60 s was used to induce lesions through the endocardial and epicardial walls of the cardiac samples. Following lesion creation, the ablated tissue samples were placed in 25 degrees C saline to allow for multi-wavelength PA imaging. Samples were imaged with a Vevo (r) 2100 ultrasound system (VisualSonics, Inc.) using a modified 20-MHz array that could provide laser irradiation to the sample from a pulsed tunable laser (Newport Corp.) to allow for co-registered photoacoustic-ultrasound (PAUS) imaging. PA imaging was conducted from 750-1064 nm, with a surface fluence of approximately 15 mJ/cm2 maintained during imaging. In this preliminary study with PA imaging, the ablated region could be well visualized on the surface of the sample, with contrasts of 6-10 dB achieved at 750 nm. Although imaging penetration depth is a concern, PA imaging shows promise in being able to reliably visualize RF ablation lesions. PMID- 26366036 TI - The Gifted Rating Scales-School Form: A Validation Study Based on Age, Gender, and Race. AB - This study examined the internal consistency and validity of a new rating scale to identify gifted students, the Gifted Rating Scales-School Form (GRS-S). The study explored the effect of gender, race/ethnicity, age, and rater familiarity on GRS-S ratings. One hundred twenty-two students in first to eighth grade from elementary and middle schools in the southeastern United States participated in the investigation. Results indicated high internal consistency for the six GRS-S scales: Intellectual Ability, Academic Ability, Creativity, Artistic Talent, Leadership, and Motivation. Results revealed no effect of race/ethnicity, age, or rater familiarity with the student. There was no significant effect for gender, although a trend was noted for girls rated slightly higher than boys across all scales. This trend was consistent with analyses of the standardization data and with cross-cultural findings using translated versions of the GRS-S. The present findings provided support for the GRS-S as a valid gifted screening instrument. PMID- 26366037 TI - Sustained Implementation of Cognitive-Behavioral Therapy for Youth Anxiety and Depression: Long-term Effects of Structured Training and Consultation on Therapist Practice in the Field. AB - Identifying factors that promote sustained implementation of evidence-based treatments (EBTs) after therapists receive training is critical for professional psychology. To address the field's minimal knowledge in this area, we interviewed community-based therapists (N = 23) who had completed intensive training in cognitive behavioral therapy (CBT) for either anxiety or depression as part of a randomized effectiveness trial (Southam-Gerow et al., 2010; Weisz et al., 2009). Therapists were interviewed three to five years after completion of the initial trial, representing one of the longest-term follow-ups of therapist practices after training. Therapists viewed each protocol and their individual CBT strategies as effective and appropriate for the majority of their current anxiety and depression caseloads. However, therapists used parts of each protocol much more frequently than the protocol as a whole (i.e., 78.5% used parts of the Coping Cat, and 7.5% used the whole protocol; 58.6% used parts of the PASCET, and 20% used the whole protocol). Therapists reported using problem-solving the most and exposure exercises the least for current anxious cases; they used cognitive restructuring the most and homework the least for current depression cases. Interventions that were more difficult to implement in usual care settings were less likely to be sustained. Future efforts should evaluate the characteristics and structure of EBTs that are most acceptable to therapists and should investigate which kinds of ongoing learning supports will maintain therapist skills in and continued use of EBTs. PMID- 26366038 TI - Identification of Noise Sources and Design of Noise Reduction Measures for a Pneumatic Nail Gun. AB - An experimental-analytical procedure was implemented to reduce the operating noise level of a nail gun, a commonly found power tool in a construction site. The procedure is comprised of preliminary measurements, identification and ranking of major noise sources and application of noise controls. Preliminary measurements show that the impact noise transmitted through the structure and the exhaust related noise were found to be the first and second major contributors. Applying a noise absorbing foam on the outside of the nail gun body was found to be an effective noise reduction technique. One and two-volume small mufflers were designed and applied to the exhaust side of the nail gun which reduced not only the exhaust noise but also the impact noise. It was shown that the overall noise level could be reduced by as much as 3.5 dB, suggesting that significant noise reduction is possible in construction power tools without any significant increase of the cost. PMID- 26366039 TI - "It felt good but weird at the same time": Emerging adults' first experiences of six different sexual behaviors. AB - Although sexual behavior is multidimensional, little research has focused on the experience of non-intercourse behaviors for adolescents and emerging adults. This paper uses open-ended coded data from a longitudinal study of college students (N = 346; Mean age = 18.5, 52% female, 27% Hispanic/Latino [HL], 25% non-HL European American, 23% non-HL Asian American, 16% non-HL African American, 9% non-HL Multiracial) to examine what emotional responses emerging adults report about their first experiences of six sexual behaviors. The four most common emotional reactions were happy, excited, fearful, and indifferent. Descriptions were largely positive, although mixed reactions were relatively common and emotional reactions varied by behavior. Results suggest the importance of including multiple types of sexual behaviors, as well as their possible positive and negative outcomes, in sexuality education programs. PMID- 26366041 TI - PREP for Strong Bonds: A review of outcomes from a randomized clinical trial. AB - To help address the relationship needs of service members, there have been a number of programs offered within active duty and veteran contexts. One program, offered within the Strong Bonds portfolio delivered by Army Chaplains, is PREP for Strong Bonds (PREP = the Prevention and Relationship Education Program). PREP has a number of empirically based and tested variants. This article reviews the disseminated research regarding results from a large randomized clinical trial designed to test the effectiveness of PREP for Strong Bonds. From a sample of 662 Army couples drawn from two sites, outcome papers have focused on different subsamples, marital outcomes, follow up time points, and moderators. Reviewing these disseminated outcomes, we conclude that PREP for Strong Bonds has significant divorce reduction effects at one site; these divorce effects were found at both one and two years post intervention, and were moderated by factors such as minority status, economic strain, and cohabitation history of the couple. In terms of marital quality outcomes, some modest overall effects were found pre to post intervention, but there were no overall marital quality outcome effects two years post intervention. However, marital quality outcomes are significantly moderated by infidelity and cohabitation history, with couples reporting these risk factors showing greater positive marital quality outcomes. These results to date are discussed in terms of clinical and research implications as well as directions for future work, such as examining longer term preventative effects. PMID- 26366043 TI - Development and Validation of a Principal Implementation Practices Measure: The Principal Implementation Questionnaire. AB - Measurement of principal implementation behaviors has proved difficult to researchers in educational leadership due to a lack of consensus on the operational definitions of leadership constructs. The Principal Implementation Questionnaire (PIQ) was developed and validated with the intention of providing clarity in the assessment of principal leadership behaviors in the implementation of effective reading programs. Constructs were operationally defined within the context of the population of interest, with subsequent item writing centered around the constructs. A resulting calibration sample of principals from Florida Reading First schools was used to test the hypothesized measurement model to determine how well the items were described by the proposed factors. Results from LISREL analyses revealed a well-fitted model, based on numerous fit indices. PMID- 26366042 TI - Mitigation effectiveness for improving nesting success of greater sage-grouse influenced by energy development. AB - Sagebrush (Artemisia spp.) habitats being developed for oil and gas reserves are inhabited by sagebrush obligate species-including the greater sage-grouse (Centrocercus urophasianus; sage-grouse) that is currently being considered for protection under the U.S. Endangered Species Act. Numerous studies suggest increasing oil and gas development may exacerbate species extinction risks. Therefore, there is a great need for effective on-site mitigation to reduce impacts to co-occurring wildlife such as sage-grouse. Nesting success is a primary factor in avian productivity and declines in nesting success are also thought to be an important contributor to population declines in sage-grouse. From 2008 to 2011 we monitored 296 nests of radio-marked female sage-grouse in a natural gas (NG) field in the Powder River Basin, Wyoming, USA and compared nest survival in mitigated and non-mitigated development areas and relatively unaltered areas to determine if specific mitigation practices were enhancing nest survival. Nest survival was highest in relatively unaltered habitats followed by mitigated, and then non-mitigated NG areas. Reservoirs used for holding NG discharge water had the greatest support as having a direct relationship to nest survival. Within a 5 km2 area surrounding a nest, the probability of nest failure increased by about 15% for every 1.5 km increase in reservoir water edge. Reducing reservoirs was a mitigation focus and sage-grouse nesting in mitigated areas were exposed to almost half of the amount of water edge compared to those in non-mitigated areas. Further, we found that an increase in sagebrush cover was positively related to nest survival. Consequently, mitigation efforts focused on reducing reservoir construction and reducing surface disturbance, especially when the surface disturbance results in sagebrush removal, are important to enhancing sage-grouse nesting success. PMID- 26366040 TI - Evidence-Based Strategies for Preserving Mobility for Elderly and Aging Manual Wheelchair Users. AB - Elderly and aging manual wheelchair (MWC) users have increased risk for accelerated loss of function and mobility that greatly limits independence and affects quality of life. This review paper addresses important issues for preserving function and mobility for elderly and aging individuals who use a MWC by presenting the current available evidence and recommendations. These include recommendations for maximizing function, by decreasing pain, improving the ability to self-propel, and prolonging mobility and endurance through ergonomics, individualized wheelchair selection and configuration, and adaptations for increasing the capacity to handle the daily mobility demands through training, strengthening, and exercise. Each recommendation is supported by current research in each relevant area. PMID- 26366044 TI - Path Following in the Exact Penalty Method of Convex Programming. AB - Classical penalty methods solve a sequence of unconstrained problems that put greater and greater stress on meeting the constraints. In the limit as the penalty constant tends to infinity, one recovers the constrained solution. In the exact penalty method, squared penalties are replaced by absolute value penalties, and the solution is recovered for a finite value of the penalty constant. In practice, the kinks in the penalty and the unknown magnitude of the penalty constant prevent wide application of the exact penalty method in nonlinear programming. In this article, we examine a strategy of path following consistent with the exact penalty method. Instead of performing optimization at a single penalty constant, we trace the solution as a continuous function of the penalty constant. Thus, path following starts at the unconstrained solution and follows the solution path as the penalty constant increases. In the process, the solution path hits, slides along, and exits from the various constraints. For quadratic programming, the solution path is piecewise linear and takes large jumps from constraint to constraint. For a general convex program, the solution path is piecewise smooth, and path following operates by numerically solving an ordinary differential equation segment by segment. Our diverse applications to a) projection onto a convex set, b) nonnegative least squares, c) quadratically constrained quadratic programming, d) geometric programming, and e) semidefinite programming illustrate the mechanics and potential of path following. The final detour to image denoising demonstrates the relevance of path following to regularized estimation in inverse problems. In regularized estimation, one follows the solution path as the penalty constant decreases from a large value. PMID- 26366045 TI - Strategic parenting, birth order, and school performance. AB - Fueled by new evidence, there has been renewed interest about the effects of birth order on human capital accumulation. The underlying causal mechanisms for such effects remain unsettled. We consider a model in which parents impose more stringent disciplinary environments in response to their earlier-born children's poor performance in school in order to deter such outcomes for their later-born offspring. We provide robust empirical evidence that school performance of children in the National Longitudinal Study Children (NLSY-C) declines with birth order as does the stringency of their parents' disciplinary restrictions. When asked how they will respond if a child brought home bad grades, parents state that they would be less likely to punish their later-born children. Taken together, these patterns are consistent with a reputation model of strategic parenting. PMID- 26366047 TI - Social Networks in Later Life: Weighing Positive and Negative Effects on Health and Well-Being. AB - Social networks provide a mix of positive and negative experiences. Network members can provide help in times of need and day-to-day companionship, but they can also behave in ways that are inconsiderate, hurtful, or intrusive. Researchers must grapple with these dualities in order to develop a comprehensive understanding of how social network ties affect health and well-being. This article provides an overview of research that has examined the health-related effects of positive and negative aspects of social network involvement. If focuses on later life, a time when risks for declining health and for the loss or disruption of social relationships increase. PMID- 26366046 TI - Auditory evoked potential audiometry in fish. AB - A recent survey lists more than 100 papers utilizing the auditory evoked potential (AEP) recording technique for studying hearing in fishes. More than 95 % of these AEP-studies were published after Kenyon et al. introduced a non invasive electrophysiological approach in 1998 allowing rapid evaluation of hearing and repeated testing of animals. First, our review compares AEP hearing thresholds to behaviorally gained thresholds. Second, baseline hearing abilities are described and compared in 111 fish species out of 51 families. Following this, studies investigating the functional significance of various accessory hearing structures (Weberian ossicles, swim bladder, otic bladders) by eliminating these morphological structures in various ways are dealt with. Furthermore, studies on the ontogenetic development of hearing are summarized. The AEP-technique was frequently used to study the effects of high sound/noise levels on hearing in particular by measuring the temporary threshold shifts after exposure to various noise types (white noise, pure tones and anthropogenic noises). In addition, the hearing thresholds were determined in the presence of noise (white, ambient, ship noise) in several studies, a phenomenon termed masking. Various ecological (e.g., temperature, cave dwelling), genetic (e.g., albinism), methodical (e.g., ototoxic drugs, threshold criteria, speaker choice) and behavioral (e.g., dominance, reproductive status) factors potentially influencing hearing were investigated. Finally, the technique was successfully utilized to study acoustic communication by comparing hearing curves with sound spectra either under quiet conditions or in the presence of noise, by analyzing the temporal resolution ability of the auditory system and the detection of temporal, spectral and amplitude characteristics of conspecific vocalizations. PMID- 26366048 TI - Learning from gesture: How our hands change our minds. AB - When people talk, they gesture, and those gestures often reveal information that cannot be found in speech. Learners are no exception. A learner's gestures can index moments of conceptual instability, and teachers can make use of those gestures to gain access into a student's thinking. Learners can also discover novel ideas from the gestures they produce during a lesson, or from the gestures they see their teachers produce. Gesture thus has the power not only to reflect a learner's understanding of a problem, but also to change that understanding. This review explores how gesture supports learning across development, and ends by offering suggestions for ways in which gesture can be recruited in educational settings. PMID- 26366049 TI - "We're Supposed to Be Asleep?" Vigilance, Paranoia, and the Alert Methamphetamine User. AB - The stimulant "benefits" of amphetamine and its derivative, methamphetamine, have endured since the drugs first became popular nearly a century ago. The concepts of increasing energy for functional purposes related to work and productivity have been well studied. However, the broader idea of increased alertness, and what this means in the lives of users, has not yet been sufficiently examined. This article draws from ongoing research with active methamphetamine users to explore the perceived benefits, drawbacks, and meanings of remaining alert-awake and vigilant-while most of the world sleeps. The experiences of several users are situated in the contexts of sociostructural and mental health issues that shape cycles of use and meanings of addiction. PMID- 26366050 TI - Parent-Child Automaticity: Links to Child Coping and Behavior and Engagement in Parent Training. AB - This research investigated parent-child automaticity (i.e., automatic ways of thinking, feeling, and interacting) as it relates to child coping and behavior and caregiver engagement in a preventive parenting program, as well as program related changes in automaticity. 610 caregivers (93% mothers) of children ages 3 6 years (52% boys; 49% African American) enrolled in the Parenting our Children to Excellence (PACE) program, and completed pre- and post- intervention assessments (N = 544 at post-intervention). Daycare providers also provided reports of school coping and behavior. Parent-child automaticity predicted parent and teacher- reported child social coping and aggressive behavior. Contrary to hypotheses, parents reporting elevated parent-child automaticity attended significantly more PACE sessions. A significant time x attendance interaction indicated decreased automaticity following the PACE program. Parent-child automaticity during the preschool years is an important correlate of child behavior and coping, and may be a motivating factor for parents to attend parent training programs. PMID- 26366052 TI - A Virtual Radial Arm Maze for the Study of Multiple Memory Systems in a Functional Magnetic Resonance Imaging Environment. AB - An increasing number of functional brain imaging studies are employing computer based virtual reality (VR) to study changes in brain activity during the performance of high-level psychological and cognitive tasks. We report the development of a VR radial arm maze that adapts for human use in a scanning environment with the same general experimental design of behavioral tasks as that has been used with remarkable effectiveness for the study of multiple memory systems in rodents. The software platform is independent of specific computer hardware and operating systems, as we aim to provide shared access to this technology by the research community. We hope that doing so will provide greater standardization of software platform and study paradigm that will reduce variability and improve the comparability of findings across studies. We report the details of the design and implementation of this platform and provide information for downloading of the system for demonstration and research applications. PMID- 26366053 TI - Comparative analysis of the development of collateral vessels in macular edema due to branch retinal vein occlusion following grid laser or ranibizumab treatment. AB - PURPOSE: To evaluate the differences in the development of collateral vessels in patients with macular edema due to branch retinal vein occlusion (BRVO) after treatment with either grid laser or ranibizumab (RNB). METHODS: Comparative study including patients with macular edema due to acute BRVO and best-corrected visual acuity (BCVA) between 20/40 and 20/200. The sample was divided into two groups according to the treatment applied: laser group, including eyes treated with Argon laser when retinal hemorrhages were sufficiently absorbed to perform the treatment, and RNB group, including patients treated initially with one monthly intravitreal injection for a period of 3 months of RNB and more injections according to need thereafter. Before treatment patients in both groups, received a complete ophthalmic examination, including BCVA, fundus examination, optical coherence tomography, fundus color photography, and fundus fluorescein angiography (FA). This same protocol of examination was repeated in every visit after treatment, except FA that was only repeated every 3 months. The detection of the collateral vessels was done by two experienced examiners based on the analysis of the early phase of the FA. If there was a discrepancy in their judgment, the criterion of a third examiner evaluating the FA was considered. RESULTS: Mean baseline BCVA was 0.86+/-0.26 and 0.82+/-0.25 (logMAR [logarithm of the minimum angle of resolution]) in the RNB and laser groups, respectively (P=0.83). At the end of the follow-up, mean BCVA was 0.38+/-0.18 and 0.64+/-0.33 (logMAR) in the RNB and laser groups, respectively. The difference in the final BCVA between both groups was statistically significant (P=0.002). Collaterals developed in both groups; 66.67% of patients (14 out of 21 patients) developed collaterals at a mean time of 6.14+/-2.60 months after diagnosis in the RNB group, and 68.18% (16 out of 22 patients) developed collaterals in the laser group at a mean time of 6.2+/-1.97 months after diagnosis. No statistically significant differences between groups were found in the number of cases developing collateral vessels (P=1.00) as well as in the time required for such development (P=0.947). CONCLUSION: The use of RNB for the treatment of macular edema due to BRVO does not seem to alter the development of collateral vessels. Future studies with larger samples are required to confirm these outcomes. PMID- 26366051 TI - Glycation, oxidation, and lipoxidation in the development of the complications of diabetes: a carbonyl stress hypothesis. AB - Modifications of extant plasma proteins, structural proteins, and other macromolecules are enhanced in diabetes because of increased glycation (secondary to increased glucose concentrations) and perhaps because of increased oxidative stress. Increased glycation is present from the time of onset of diabetes, but the relation between diabetes and oxidative stress is less clear: increased oxidative stress may occur later in the course of disease, as vascular damage becomes established, or it may be a feature of uncomplicated diabetes. The combined effects of protein modification by glycation and oxidation may contribute to the development of accelerated atherosclerosis in diabetes and to the development of microvascular complications. Thus, even if not increased by diabetes, variations in oxidative stress may modulate the consequences of hyperglycemia in individual diabetic patients. In this review, the close interaction between glycation and oxidative processes is discussed, and the theme is developed that the most significant modifications of proteins are the result of interactions with reactive carbonyl groups. While glucose itself contains a carbonyl group that is involved in the initial glycation reaction, the most important and reactive carbonyls are formed by free radical-oxidation reactions damaging either carbohydrates (including glucose itself) or lipids. The resulting carbonyl-containing intermediate products then modify proteins, yielding "glycoxidation" and "lipoxidation" products, respectively. This common pathway for glucose and lipid-mediated stress, which may contribute to diabetic complications, is the basis for the carbonyl stress hypothesis for the development of diabetic complications. PMID- 26366054 TI - Epidemiological evaluation of YAG capsulotomy incidence for posterior capsule opacification in various intraocular lenses in Japanese eyes. AB - BACKGROUND AND OBJECTIVE: We investigated the yttrium aluminum garnet (YAG) capsulotomy rates in various intraocular lenses (IOLs). STUDY DESIGN/PATIENTS AND METHODS: We retrospectively analyzed 23,440 eyes implanted with either MA60BM, MA60AC, VA-60BB, CeeOnEdge, Clariflex, Technis Z9002, SI-40NB, or UV26T IOLs. We calculated the YAG capsulotomy rates at 1, 3, 5, and 10 years post lens implantation. RESULTS: YAG capsulotomy rates at 3 years postimplantation for the eight groups of IOLs were, respectively, 3.7%, 3.9%, 23.7%, 3.4%, 4.5%, 4.7%, 10.4%, and 21.0%. YAG capsulotomy rates at 10 years postimplantation for the MA60BM and SI-40NB IOLs were, respectively, 9.1% and 15% (P<0.05). The average YAG rates for all sharp-edged and round-edged IOLs at 5 years postimplantation were, respectively, 5.2%+/-0.7% and 25.6%+/-9.0% (P<0.05). CONCLUSION: In all studied IOLs, posterior capsule opacification prevention seemed to be associated with the posterior optic sharp-edge design. Round-edged silicone IOLs may also retard posterior capsule opacification formation, though not as much as sharp edged IOLs. As the follow-up period progressed, round-edged silicone IOLs showed significantly higher YAG rates than sharp-edged IOLs. PMID- 26366055 TI - Pseudoexfoliation syndrome at a Singapore eye clinic. AB - BACKGROUND: The purpose of this study was to investigate the demographics of pseudoexfoliation syndrome (PXF) and pseudoexfoliative glaucoma (PXG) in a Singapore hospital eye outpatient clinic. METHODS: A retrospective study of 93 consecutive patients (146 eyes) with PXF was undertaken by a single ophthalmologist over a period of 37 months (July 1, 2006, to July 31, 2009). RESULTS: Ninety-three (2.8%) of 3,297 patients seen during the study period were diagnosed with PXF. Forty-three (46.2%) of the 93 PXF patients were male. Indians were 5.04 times more likely to develop PXF than Chinese (P<0.001, 95% confidence interval 3.05-8.33), while Malays were 2.22 times more likely to develop PXF as compared with Chinese (P=0.029, 95% CI 1.08-4.55). Twenty-two (23.7%) of the 93 PXF patients had PXG at the time of diagnosis. There was no statistically significant difference in mean age between PXF and PXG patients. There was a larger proportion of males with PXG than females (P<0.001). CONCLUSION: PXF is not infrequent in elderly Singapore eye clinic patients, and is more likely to occur in Indians than in Chinese. In the Singapore eye clinic setting, males may be more likely to develop PXG, although larger studies will be required to confirm this. PMID- 26366056 TI - Inhibition of HIV-1 by curcumin A, a novel curcumin analog. AB - Despite the remarkable success of combination antiretroviral therapy at curtailing HIV progression, emergence of drug-resistant viruses, chronic low grade inflammation, and adverse effects of combination antiretroviral therapy treatments, including metabolic disorders collectively present the impetus for development of newer and safer antiretroviral drugs. Curcumin, a phytochemical compound, was previously reported to have some in vitro anti-HIV and anti inflammatory activities, but poor bioavailability has limited its clinical utility. To circumvent the bioavailability problem, we derivatized curcumin to sustain retro-aldol decomposition at physiological pH. The lead compound derived, curcumin A, showed increased stability, especially in murine serum where it was stable for up to 25 hours, as compared to curcumin that only had a half-life of 10 hours. Both curcumin and curcumin A showed similar inhibition of one round of HIV-1 infection in cultured lymphoblastoid (also called CEM) T cells (IC50=0.7 MUM). But in primary peripheral blood mononuclear cells, curcumin A inhibited HIV 1 more potently (IC50=2 MUM) compared to curcumin (IC50=12 MUM). Analysis of specific steps of HIV-1 replication showed that curcumin A inhibited HIV-1 reverse transcription, but had no effect on HIV-1 long terminal repeat basal or Tat-induced transcription, or NF-kappaB-driven transcription at low concentrations that affected reverse transcription. Finally, we showed curcumin A induced expression of HO-1 and decreased cell cycle progression of T cells. Our findings thus indicate that altering the core structure of curcumin could yield more stable compounds with potent antiretroviral and anti-inflammatory activities. PMID- 26366057 TI - Paeonia lactiflora Pall. protects against ANIT-induced cholestasis by activating Nrf2 via PI3K/Akt signaling pathway. AB - BACKGROUND: Paeonia lactiflora Pall. (PLP), a traditional Chinese herbal medicine, has been used for hepatic disease treatment over thousands of years. In our previous study, PLP was shown to demonstrate therapeutic effect on hepatitis with severe cholestasis. The aim of this study was to evaluate the antioxidative effect of PLP on alpha-naphthylisothiocyanate (ANIT)-induced cholestasis by activating NF-E2-related factor 2 (Nrf2) via phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. MATERIALS AND METHODS: Liquid chromatography-mass spectrometry (LC-MS) was performed to identify the main compounds present in PLP. The mechanism of action of PLP and its therapeutic effect on cholestasis, induced by ANIT, were further investigated. Serum indices such as total bilirubin (TBIL), direct bilirubin (DBIL), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (gamma-GT), and total bile acid (TBA) were measured, and histopathology of liver was also performed to determine the efficacy of treatment with PLP. Moreover, in order to illustrate the underlying signaling pathway, liver glutathione (GSH) content and mRNA or protein levels of glutamate-cysteine ligase catalytic subunit (GCLc), glutamate-cysteine ligase modulatory subunit (GCLm), Akt, heme oxygenase 1 (HO-1), NAD(P)H/quinone oxidoreductase 1 (Nqo1), and Nrf2 were further analyzed. In addition, validation of PLP putative target network was also performed in silico. RESULTS: Four major compounds including paeoniflorin, albiflorin, oxypaeoniflorin, and benzoylpaeoniflorin were identified by LC-MS analysis in water extract of PLP. Moreover, PLP could remarkably downregulate serum levels of TBIL, DBIL, AST, ALT, ALP, gamma-GT, and TBA, and alleviate the histological damage of liver tissue caused by ANIT. It enhanced antioxidative system by activating PI3K/Akt/Nrf2 pathway through increasing Akt, Nrf2, HO-1, Nqo1, GCLc, and GCLm expression. The putative targets network validation also confirmed the important role of PLP in activating Akt expression. CONCLUSION: The potential mechanism of PLP in alleviating ANIT-induced cholestasis could to be related to the induction of GSH synthesis by activating Nrf2 through PI3K/Akt dependent pathway. This indicates that PLP might be a potential therapeutic agent for cholestasis. PMID- 26366058 TI - Phase III study of pasireotide long-acting release in patients with metastatic neuroendocrine tumors and carcinoid symptoms refractory to available somatostatin analogues. AB - In a randomized, double-blind, Phase III study, we compared pasireotide long acting release (pasireotide LAR) with octreotide long-acting repeatable (octreotide LAR) in managing carcinoid symptoms refractory to first-generation somatostatin analogues. Adults with carcinoid tumors of the digestive tract were randomly assigned (1:1) to receive pasireotide LAR (60 mg) or octreotide LAR (40 mg) every 28 days. Primary outcome was symptom control based on frequency of bowel movements and flushing episodes. Objective tumor response was a secondary outcome. Progression-free survival (PFS) was calculated in a post hoc analysis. Adverse events were recorded. At the time of a planned interim analysis, the data monitoring committee recommended halting the study because of a low predictive probability of showing superiority of pasireotide over octreotide for symptom control (n=43 pasireotide LAR, 20.9%; n=45 octreotide LAR, 26.7%; odds ratio, 0.73; 95% confidence interval [CI], 0.27-1.97; P=0.53). Tumor control rate at month 6 was 62.7% with pasireotide and 46.2% with octreotide (odds ratio, 1.96; 95% CI, 0.89-4.32; P=0.09). Median (95% CI) PFS was 11.8 months (11.0 - not reached) with pasireotide versus 6.8 months (5.6 - not reached) with octreotide (hazard ratio, 0.46; 95% CI, 0.20-0.98; P=0.045). The most frequent drug-related adverse events (pasireotide vs octreotide) included hyperglycemia (28.3% vs 5.3%), fatigue (11.3% vs 3.5%), and nausea (9.4% vs 0%). We conclude that, among patients with carcinoid symptoms refractory to available somatostatin analogues, similar proportions of patients receiving pasireotide LAR or octreotide LAR achieved symptom control at month 6. Pasireotide LAR showed a trend toward higher tumor control rate at month 6, although it was statistically not significant, and was associated with a longer PFS than octreotide LAR. PMID- 26366059 TI - Distinct prognostic values and potential drug targets of ALDH1 isoenzymes in non small-cell lung cancer. AB - Increased aldehyde dehydrogenase 1 (ALDH1) activity has been found in the stem cell populations of leukemia and some solid tumors including non-small-cell lung cancer (NSCLC). However, which ALDH1's isoenzymes are contributing to ALDH1 activity remains elusive. In addition, the prognostic value of individual ALDH1 isoenzyme is not clear. In the current study, we investigated the prognostic value of ALDH1 isoenzymes in NSCLC patients through the Kaplan-Meier plotter database, which contains updated gene expression data and survival information from a total of 1,926 NSCLC patients. High expression of ALDH1A1 mRNA was found to be correlated to a better overall survival (OS) in all NSCLC patients followed for 20 years (hazard ratio [HR] 0.88 [0.77-0.99], P=0.039). In addition, high expression of ALDH1A1 mRNA was also found to be correlated to better OS in adenocarcinoma (Ade) patients (HR 0.71 [0.57-0.9], P=0.0044) but not in squamous cell carcinoma (SCC) patients (HR 0.92 [0.72-1.16], P=0.48). High expression of ALDH1A2 and ALDH1B1 mRNA was found to be correlated to worser OS in all NSCLC patients, as well as in Ade, but not in SCC patients. High expression of both ALDH1A3 and ALDH1L1 mRNA was not found to be correlated to OS in all NSCLC patients. These results strongly support that ALDH1A1 mRNA in NSCLC is associated with better prognosis. In addition, our current study also supports that ALDH1A2 and ALDH1B1 might be major contributors to the ALDH1 activity in NSCLC, since high expression of ALDH1A2 and ALDH1B1 mRNA was found to be significantly correlated to worser OS in all NSCLC patients. Based on our study, ALDH1A2 and ALDH1B1 might be excellent potential drug targets for NSCLC patients. PMID- 26366061 TI - Perceived quality of health care services among people with osteoarthritis - results from a nationwide survey. AB - OBJECTIVE: To assess the perceived quality of care received by people with osteoarthritis (OA) in Norway and explore factors associated with the quality of care. METHODS: A national survey in which members of the Norwegian Rheumatism Association with OA registered as their main diagnosis completed a questionnaire. The perceived quality of care was reported on a 17-item OsteoArthritis Quality Indicator questionnaire, covering both pharmacological and non-pharmacological aspects of OA care. In addition, the four-page questionnaire covered areas related to demographic characteristics, the location and impact of the OA, and utilization and satisfaction with health care services. The quality of care is calculated as pass rates, where the numerator represents the number of indicators passed and the denominator represents the number of eligible persons. RESULTS: In total, 1,247 participants (response rate 57%) completed the questionnaire. Mean age was 68 years (standard deviation 32) and 1,142 (92%) were women. Respondents reported OA in hand only (12.4%), hip only (7.3%), knee only (10.4%), in two locations (42%) or all three locations (27%). The overall OsteoArthritis Quality Indicator pass rate was 47% (95% confidence interval [CI] 46%-48%), and it was higher for pharmacological aspects (53% [51%-54%]) than for non-pharmacological aspects of care (44% [43%-46%]). The pass rate for the individual quality indicators ranged from 8% for "referral for weight reduction" to 81% for "receiving advice about exercises". Satisfaction with care was strongly associated with perceived quality. The pass rate for those who were "very satisfied" was 33% (25%-40%) higher than those who were "very unsatisfied" with care. CONCLUSION: While the OA patient seems to be rather satisfied with the perceived OA care, there is still room for improvement in the quality of care. Although the quality of care in the present study is somewhat higher than in other studies, less than 50% of the recommended care has been provided. PMID- 26366060 TI - Empowerment, motivation, and medical adherence (EMMA): the feasibility of a program for patient-centered consultations to support medication adherence and blood glucose control in adults with type 2 diabetes. AB - PURPOSE: To explore the feasibility of a research-based program for patient centered consultations to improve medical adherence and blood glucose control in patients with type 2 diabetes. PATIENTS AND METHODS: The patient-centered empowerment, motivation, and medical adherence (EMMA) consultation program consisted of three individual consultations and one phone call with a single health care professional (HCP). Nineteen patients with type 2 diabetes completed the feasibility study. Feasibility was assessed by a questionnaire-based interview with patients 2 months after the final consultation and interviews with HCPs. Patient participation was measured by 10-second event coding based on digital recordings and observations of the consultations. RESULTS: HCPs reported that EMMA supported patient-centered consultations by facilitating dialogue, reflection, and patient activity. Patients reported that they experienced valuable learning during the consultations, felt understood, and listened to and felt a trusting relationship with HCPs. Consultations became more person specific, which helped patients and HCPs to discover inadequate diabetes self management through shared decision-making. Compared with routine consultations, HCPs talked less and patients talked more. Seven of ten dialogue tools were used by all patients. It was difficult to complete the EMMA consultations within the scheduled time. CONCLUSION: The EMMA program was feasible, usable, and acceptable to patients and HCPs. The use of tools elicited patients' perspectives and facilitated patient participation and shared decision-making. PMID- 26366062 TI - Efficacy of a trunk orthosis with joints providing resistive force on low-back load in elderly persons during static standing. AB - PURPOSE: Postural alignment of elderly people becomes poor due to aging, possibly leading to low-back pain and spinal deformity. Although there are several interventions for treating these conditions, no previous study has reported the effectiveness of a spinal orthosis or lumbosacral orthosis (LSO) in healthy elderly people without specific spinal deformity. We therefore developed a trunk orthosis to decrease low-back muscle activity while training good postural alignment through resistive force provided by joints with springs (here, called the ORF, which stands for orthosis with joints providing resistive force) as a preventive method against abnormal posture and low-back pain in healthy elderly persons. PATIENTS AND METHODS: Fifteen community-dwelling elderly men participated in this study. Participants stood freely for 10 seconds in a laboratory setting under three conditions: without an orthosis, with the ORF, and with an LSO. The Damen corset LSO was selected as it is frequently prescribed for patients with low-back pain. Postural alignment during static standing was recorded using a three-dimensional motion capture system employing infrared cameras. Two force plates were used to record center of pressure. Electromyograms were obtained for bilateral erector spinae (ES), left internal abdominal oblique, and right gluteus medius muscles. RESULTS: Pelvis forward tilt angle tended to increase while wearing the ORF and decrease while wearing the LSO, but these results were not significant compared to no orthosis. Thorax extension angle and thorax angle on pelvis coordinate system significantly increased while wearing the ORF compared to the other two conditions. ES activity significantly decreased while wearing the ORF compared to the other two conditions. Internal oblique activity was significantly smaller while wearing the LSO than with no orthosis. Center of pressure did not significantly differ among the conditions. CONCLUSION: The ORF significantly improved trunk alignment and decreased ES activity in healthy elderly subjects during static standing. PMID- 26366063 TI - The role of citicoline in cognitive impairment: pharmacological characteristics, possible advantages, and doubts for an old drug with new perspectives. AB - BACKGROUND: Citicoline is able to potentiate neuroplasticity and is a natural precursor of phospholipid synthesis, or rather serves as a choline source in the metabolic pathways for biosynthesis of acetylcholine. Several studies have shown that it can have beneficial effects both in degenerative and in vascular cognitive decline. The aim of the present study was to review the pharmacokinetics and pharmacodynamics of this drug and its role in cognitive impairment according to the present medical literature. METHODS: A MEDLINE((r)) search was made using the following key words: citicoline, pharmacokinetics, pharmacodynamics, elderly, cognitive impairment, vascular dementia, and Alzheimer's disease. Recent studies on the possible role of citicoline in increasing sirtuin 1 (SIRT1) expression were assessed. Some personal studies were also considered, such as the VITA study and the IDEALE study. RESULTS: Administered by both oral and intravenous routes, citicoline is converted into two major circulating metabolites, cytidine and choline. It is metabolized in the gut wall and liver. Pharmacokinetic studies suggested that it is well absorbed and highly bioavailable with oral dosing. A number of studies have clearly shown the possible role of citicoline in cognitive impairment of diverse etiology. It can also modulate the activity/expression of some protein kinases involved in neuronal death and increases SIRT1 expression in the central nervous system. The VITA study and the IDEALE study suggested that both parenteral and oral citicoline are effective and safe. Other studies have clearly demonstrated citicoline's effects on several cognitive domains. Conversely, some studies did not point out any evidence of efficacy of this drug. CONCLUSION: Citicoline appears to be a promising agent to improve cognitive impairment, especially of vascular origin. In fact, so far it appears as a drug with the ability to promote "safe" neuroprotection, capable of enhancing endogenous protective. Large clinical trials are needed to confirm its benefits. PMID- 26366064 TI - Stroke prevention in the elderly atrial fibrillation patient with comorbid conditions: focus on non-vitamin K antagonist oral anticoagulants. AB - Stroke prevention in elderly atrial fibrillation patients remains a challenge. There is a high risk of stroke and systemic thromboembolism but also a high risk of bleeding if anticoagulants are prescribed. The elderly have increased chronic kidney disease, coronary artery disease, polypharmacy, and overall frailty. For all these reasons, anticoagulant use is underutilized in the elderly. In this manuscript, the benefits of non-vitamin K antagonist oral anticoagulants compared with warfarin in the elderly patient population with multiple comorbid conditions are reviewed. PMID- 26366065 TI - Prevalence of quadriceps muscle weakness in patients with COPD and its association with disease severity. AB - INTRODUCTION: COPD presents with an array of extra-pulmonary symptoms of which skeletal muscle dysfunction, particularly of the quadriceps, is well recognized. This contributes to impaired quality of life and increased health care utilization. Work on the quadriceps originated from the observation that a good proportion of COPD patients stop exercise due to the feeling of leg fatigue rather than breathlessness. This study was carried out with the aim of finding the prevalence of quadriceps weakness in a population set and correlate it with severity of COPD. METHODOLOGY: This cross-sectional study was conducted in 75 subjects suffering from COPD aged 45 years or above. COPD severity in the subjects was graded based on the GOLD staging system. A digital hand held dynamometer (HHD) was used to measure quadriceps muscle strength. Descriptive statistics were done, and Pearson's Correlation Coefficient and ANOVA analysis was used for expressing the results. RESULTS: Ninety two percent of subjects were suffering from quadriceps muscle weakness. Quadriceps weakness was present in significantly high proportions even in those suffering from mild disease and belonging to a younger age group. The mean quadriceps muscle force value decreased with disease severity and this relation was found to be significant (P<0.01). CONCLUSION: Majority of the COPD patients were found to be suffering from quadriceps weakness, which was also present in significant proportions in subjects belonging to younger age groups and suffering from mild disease. These findings indicate that onset of muscle weakness in COPD may precede the onset of symptoms. These findings suggest need for early remedial measure to prevent occurrence of associated systemic diseases. PMID- 26366066 TI - Low bone mineral density in COPD patients with osteoporosis is related to low daily physical activity and high COPD assessment test scores. AB - COPD patients have an increased prevalence of osteoporosis (OP) compared with healthy people. Physical inactivity in COPD patients is a crucial risk factor for OP; the COPD assessment test (CAT) is the newest assessment tool for the health status and daily activities of COPD patients. This study investigated the relationship among daily physical activity (DPA), CAT scores, and bone mineral density (BMD) in COPD patients with or without OP. This study included 30 participants. Ambulatory DPA was measured using actigraphy and oxygen saturation by using a pulse oximeter. BMD was measured using dual-energy X-ray absorptiometry. OP was defined as a T-score (standard deviations from a young, sex-specific reference mean BMD) less than or equal to -2.5 SD for the lumbar spine, total hip, and femoral neck. We quantified oxygen desaturation during DPA by using a desaturation index and recorded all DPA, except during sleep. COPD patients with OP had lower DPA and higher CAT scores than those of patients without OP. DPA was significantly positively correlated with (lumbar spine, total hip, and femoral neck) BMD (r=0.399, 0.602, 0.438, respectively, all P<0.05) and T-score (r=0.471, 0.531, 0.459, respectively, all P<0.05), whereas CAT scores were significantly negatively correlated with (total hip and femoral neck) BMD (r=-0.412, -0.552, respectively, P<0.05) and (lumbar spine, total hip, and femoral neck) T-score (r=-0.389, -0.429, -0.543, respectively, P<0.05). Low femoral neck BMD in COPD patients was related to high CAT scores. Our results show no significant difference in desaturation index, low SpO2, and inflammatory markers (IL-6, TNF-alpha, IL-8/CXCL8, CRP, and 8-isoprostane) between the two groups. Chest physicians should be aware that COPD patients with OP have low DPA and high CAT scores. PMID- 26366067 TI - Is a previous diagnosis of asthma a reliable criterion for asthma-COPD overlap syndrome in a patient with COPD? AB - BACKGROUND: Some patients share characteristics of both COPD and asthma. As yet, there is no gold standard to identify patients with the so-called asthma-COPD overlap syndrome (ACOS). OBJECTIVE: To describe the differences between ACOS patients and the remaining COPD patients, and to compare the clinical characteristics of patients diagnosed with ACOS by two different criteria: previous diagnosis of asthma before the age of 40 years; and the diagnostic criteria of the Spanish guidelines of COPD. METHODS: Multicenter, observational, cross-sectional study performed in 3,125 COPD patients recruited in primary care and specialized outpatient clinics. Patients with COPD and a history of asthma before the age of 40 years were diagnosed with ACOS and compared to the remaining COPD patients. Subsequently, ACOS patients were subdivided based on whether they fulfilled the Spanish guidelines of the COPD diagnostic criteria or not, and they were compared. RESULTS: ACOS was diagnosed in 15.9% of the patients. These patients had different basal characteristics compared to the remaining COPD patients, including a higher frequency of women and more exacerbations despite lower tobacco exposure and better lung function. They were more likely to have features of asthma, such as a positive bronchodilator test, higher peripheral eosinophilia, and higher total immunoglobulin E. Within the ACOS group, only one third fulfilled the diagnostic criteria of the Spanish guidelines of COPD; these individuals were not significantly different from the remaining ACOS patients, except for having more exacerbations and poorer lung function. CONCLUSION: ACOS patients diagnosed on the basis of a previous diagnosis of asthma differed from the remaining COPD patients, but they were similar to ACOS patients diagnosed according to more restrictive criteria, suggesting that a history of asthma before the age of 40 years could be a useful criterion to suspect ACOS in a patient with COPD. PMID- 26366068 TI - Efficacy and safety of once-daily inhaled umeclidinium/vilanterol in Asian patients with COPD: results from a randomized, placebo-controlled study. AB - BACKGROUND: Combination of the inhaled long-acting muscarinic antagonist umeclidinium (UMEC; GSK573719) with the long-acting beta2-agonist vilanterol (VI) is an approved maintenance treatment for COPD in the US and EU. We compared the efficacy and safety of UMEC/VI with placebo in patients with COPD of Asian ancestry. PATIENTS AND METHODS: In this 24-week, Phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group study, patients were randomized 1:1:1 to UMEC/VI 125/25 MUg, UMEC/VI 62.5/25 MUg, or placebo. The primary efficacy end point was trough forced expiratory volume in 1 second (FEV1) on day 169; secondary end points were Transition Dyspnea Index (TDI) focal score at week 24 and weighted mean (WM) FEV1 over 0-6 hours postdose on day 1. Additional end points and safety were also assessed. RESULTS: Both UMEC/VI 125/25 MUg and UMEC/VI 62.5/25 MUg statistically significantly improved trough FEV1 at day 169 versus placebo (UMEC/VI 125/25 MUg, 0.216 L, [95% confidence interval [CI] 0.175-0.257]; UMEC/VI 62.5/25 MUg, 0.151 L, 95% CI 0.110-0.191; both P<0.001). Statistically significant improvements in TDI score were observed for both UMEC/VI groups versus placebo (UMEC/VI 125/25 MUg, 0.9, 95% CI 0.3-1.4, P=0.002; UMEC/VI 62.5/25 MUg, 0.7, 95% CI 0.1-1.2, P=0.016). On day 1, both UMEC/VI groups improved 0-6-hour WM FEV1 versus placebo (UMEC/VI 125/25 MUg, 0.182 L 95% CI 0.161-0.203; UMEC/VI 62.5/25 MUg, 0.160 L, 95% CI 0.139-0.181; both P<0.001). Statistically significant improvements for UMEC/VI groups versus placebo were observed for rescue albuterol use at weeks 1-24 (puffs/day, both P<0.001). The incidence of adverse events was similar across groups. CONCLUSION: In Asian patients with COPD, once-daily UMEC/VI 125/25 MUg and UMEC 62.5/25 MUg resulted in clinically meaningful and statistically significant improvements in lung-function end points versus placebo. Symptomatic and quality of life measures also improved. The safety profile of UMEC/VI was consistent with previous studies. PMID- 26366069 TI - Bronchodilators use in patients with COPD. AB - BACKGROUND: Bronchodilators are commonly used as maintenance and rescue therapy in patients with COPD. We aimed to examine the prescribing patterns of bronchodilators in clinical practice. METHODS: We identified patients with COPD who initiated oral or inhaled bronchodilators between 2001 and 2010 from the Taiwan National Health Insurance Research Database. We followed the patients for 1 year. For bronchodilator prescriptions, we classified the treatments based on medication classes and regimens (oral bronchodilators alone, oral and inhaled bronchodilators in combination, or inhaled bronchodilators alone). For inhaled bronchodilator prescriptions, we further classified the treatments as short acting bronchodilators alone, short-acting and long-acting bronchodilators in combination, and long-acting bronchodilators alone. We evaluated the prescribing patterns and the change with time, in different physician specialists, and in different hospital accreditation levels. RESULTS: Among a cohort of 4,387 study eligible patients, we identified 21,235 bronchodilator prescriptions for the analysis. The majority of prescriptions were oral xanthines or beta-2 agonists (62.63% and 47.54%, respectively) rather than prescriptions for inhaled bronchodilators (less than 10%). Nearly 80% of prescriptions were oral bronchodilator alone regimens. Use of oral bronchodilators declined with time and varied with health care providers, which were most commonly prescribed by non chest specialists and in primary care clinics. Despite limited use of inhaled bronchodilators, it was noted that short-acting bronchodilators alone regimens accounted for 60% of the inhaled bronchodilator prescriptions. CONCLUSION: Excessive use of oral and short-acting bronchodilators is noted in general practice. Further research and education programs are warranted to decrease inadequate oral bronchodilators and optimize inhaled treatments in the management of patients with COPD. PMID- 26366070 TI - Epidemiology of chronic obstructive pulmonary disease: a population-based study in Krasnoyarsk region, Russia. AB - BACKGROUND: Krasnoyarsk region is a territory with the widespread risk factors for chronic obstructive pulmonary disease (COPD) such as tobacco smoke, air pollution, and occupational exposure. An assessment of COPD prevalence based on medical diagnosis statistics underestimates the true COPD prevalence. This study aims to evaluate how medical examinations may increase the accuracy of estimates of COPD prevalence. METHODS: True COPD prevalence was estimated as a number of patients with the established disease diagnosis supplemented by the additional disease cases detected during medical examinations per 1,000 inhabitants of the region. Official medical statistics data and the data collected from the Global Alliance against Chronic Respiratory Diseases program 2011 among 15,000 inhabitants of the region aged 18 years and older were analyzed. RESULTS: This study revealed the COPD cases without official medical diagnosis. The true prevalence of COPD is estimated to be two times higher than the prevalence estimates based on medical diagnosis statistics. CONCLUSION: Undiagnosed and untreated cases of COPD result in severe COPD forms as well as addition of severe comorbidities. Because of this, there is an increase in the index of potential years of life lost. Conducting special medical examinations may increase the number of COPD cases detected at the early stages of the disease. This, in turn, may reduce the overall burden of the disease for the population of the region. PMID- 26366071 TI - Personalized pulmonary rehabilitation and occupational therapy based on cardiopulmonary exercise testing for patients with advanced chronic obstructive pulmonary disease. AB - TAKE-HOME SUMMARY: Personalized pulmonary rehabilitation including occupational therapy improves the prognosis of patients with advanced COPD. PURPOSE: We previously reported that patients with chronic obstructive pulmonary disease (COPD) exhibit three exercise-induced life-threatening conditions: hypoxemia, sympathetic overactivity, and respiratory acidosis. We aimed to verify whether mortality in patients with advanced COPD could be reduced by a personalized pulmonary rehabilitation (PPR) program in hospital, which determines individual safe ranges and includes occupational therapy (PPR-OT), to prevent desaturation and sympathetic nerve activation during daily activities. PATIENTS AND METHODS: The novel PPR-OT program was evaluated in a retrospective study of patients with COPD (Global Initiative for Chronic Obstructive Lung Disease [GOLD] Grade D) who underwent cardiopulmonary exercise testing (CPET) between April 1990 and December 1999. They received regular treatment without the proposed therapy (control group: n=61; male-to-female ratio [M:F] =57:4; mean age: 68.5+/-6.7 years) or with the proposed therapy (PPR-OT group: n=46; M:F =44:2; mean age: 68.7+/-7.1 years). A prospective observational study included patients with COPD receiving home oxygen therapy (HOT) between April 1995 and March 2007 to compare the survival rates of the control group (n=47; M:F ratio =34:13; mean age: 71.3+/ 10.0 years) and the PPR-OT group (n=85; M:F =78:7; mean age: 70.7+/-6.1 years) who completed the proposed therapy. Survival after CPET or HOT was analyzed using Cox proportional-hazards regression and Kaplan-Meier analyses. RESULTS: In both studies, the program significantly improved all-cause mortality (retrospective study: risk ratio =0.389 [range: 0.172-0.800]; P=0.0094; log-rank test, P=0.0094; observational study: risk ratio =0.515 [range: 0.296-0.933]; P=0.0291; log-rank test, P=0.0232]. At 5 years and 7 years, all-cause mortality was extremely low in patients in the PPR-OT group receiving HOT (18.8% and 28.2%, respectively), compared to that in the control group (34.0% and 44.7%, respectively). Survival of patients with life-threatening pathophysiological conditions also greatly improved. CONCLUSION: The PPR-OT program improved the survival of patients with advanced COPD probably because it modified life-threatening conditions. PMID- 26366072 TI - Effect of tele health care on exacerbations and hospital admissions in patients with chronic obstructive pulmonary disease: a randomized clinical trial. AB - BACKGROUND AND OBJECTIVE: Tele monitoring (TM) of patients with chronic obstructive pulmonary disease (COPD) has gained much interest, but studies have produced conflicting results. Our aim was to investigate the effect of TM with the option of video consultations on exacerbations and hospital admissions in patients with severe COPD. MATERIALS AND METHODS: Patients with severe COPD at high risk of exacerbations were eligible for the study. Of 560 eligible patients identified, 279 (50%) declined to participate. The remaining patients were equally randomized to either TM (n=141) or usual care (n=140) for the 6-month study period. TM comprised recording of symptoms, saturation, spirometry, and weekly video consultations. Algorithms generated alerts if readings breached thresholds. Both groups received standard care. The primary outcome was number of hospital admissions for exacerbation of COPD during the study period. RESULTS: Most of the enrolled patients had severe COPD (forced expiratory volume in 1 second <50%pred in 86% and >=hospital admission for COPD in the year prior to enrollment in 45%, respectively, of the patients). No difference in drop-out rate and mortality was found between the groups. With regard to the primary outcome, no significant difference was found in hospital admissions for COPD between the groups (P=0.74), and likewise, no difference was found in time to first admission or all-cause hospital admissions. Compared with the control group, TM group patients had more moderate exacerbations (ie, treated with antibiotics/corticosteroid, but not requiring hospital admission; P<0.001), whereas the control group had more visits to outpatient clinics (P<0.001). CONCLUSION: Our study of patients with severe COPD showed that TM including video consultations as add-on to standard care did not reduce hospital admissions for exacerbated COPD, but TM may be an alternative to visits at respiratory outpatient clinics. Further studies are needed to establish the optimal role of TM in the management of severe COPD. PMID- 26366073 TI - Biocompatible and biodegradable fibrinogen microspheres for tumor-targeted doxorubicin delivery. AB - In the development of effective drug delivery carriers, many researchers have focused on the usage of nontoxic and biocompatible materials and surface modification with targeting molecules for tumor-specific drug delivery. Fibrinogen (Fbg), an abundant glycoprotein in plasma, could be a potential candidate for developing drug carriers because of its biocompatibility and tumor targeting property via arginine-glycine-aspartate (RGD) peptide sequences. Doxorubicin (DOX), a chemotherapeutic agent, was covalently conjugated to Fbg, and the microspheres were prepared. Acid-labile and non-cleavable linkers were used for the conjugation of DOX to Fbg, resulting in an acid-triggered drug release under a mild acidic condition and a slow-controlled drug release, respectively. In vitro cytotoxicity tests confirmed low cytotoxicity in normal cells and high antitumor effect toward cancer cells. In addition, it was discovered that a longer linker could make the binding of cells to Fbg drug carriers easier. Therefore, DOX-linker-Fbg microspheres could be a suitable drug carrier for safer and effective drug delivery. PMID- 26366074 TI - Investigation of the biological and anti-cancer properties of ellagic acid encapsulated nano-sized metalla-cages. AB - Three new large hexanuclear metalla-prisms 9-11 incorporating 1,3, 5-tris(pyridin 4-ylethynyl)benzene (tpeb) 4 and one of the dinuclear arene ruthenium clips [Ru2(p-iPrC6H4Me)2(OO?OO)][CF3SO3]2 (OO?OO =2,5-dioxydo-1,4-benzoquinonato [dobq] 1, 5,8-dihydroxy-1,4-naphthaquinonato (donq) 2, and 6,11-dihydroxy-5,12 naphthacenedionato [dotq] 3), which encapsulate the guest molecule ellagic acid (2,3,7,8-tetrahydroxy-chromeno[5,4,3-cde]chromene-5,10-dione, 5) were prepared. All complexes were isolated as triflate salts in good yields and were fully characterized by (1)H NMR spectroscopy and electrospray ionization mass spectrometry. The photophysical properties of these metalla-prisms were also investigated. Compounds 9 and 10 showed potent antioxidant activity, but 10 had the superior ORACPE value (1.30 +/- 0.020). Ellagic acid (5) and compound 11 showed weaker activity than that of Trolox. The 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide assay showed that the metalla-prism compounds exhibit anticancer properties in vitro. Compound 10 inhibited the growth of all cancer cell lines at micromolar concentrations, with the highest cytotoxicity observed against A549 human lung cancer cells (IC50 =25.9 MUM). However, these compounds had a lower anti-cancer activity than that of doxorubicin. In a tumoricidal assay, ellagic acid (5) and compound 10 induced cytotoxicity in tumor cells, while doxorubicin did not. While free ellagic acid had no effect on the granulocyte-colony stimulating factor and regulated on activation normal T cell expressed and secreted protein, the encapsulated metalla-prism 10 stimulated granulocyte-colony stimulating factor and reduced regulated on activation normal T cell expressed and secreted protein expression in the RAW264.7 macrophage line. Our results show that ellagic acid encapsulated in metalla-prisms inhibited cancer cells via the modulation of mRNA induction and protein expression levels of the granulocyte-colony stimulating factor and regulated on activation normal T cell expressed and secreted protein in macrophages. PMID- 26366075 TI - Nanoemulsions containing a synthetic chalcone as an alternative for treating cutaneous leshmaniasis: optimization using a full factorial design. AB - Nanoemulsions are drug delivery systems that may increase the penetration of lipophilic compounds through the skin, enhancing their topical effect. Chalcones are compounds of low water solubility that have been described as promising molecules for the treatment of cutaneous leishmaniasis (CL). In this context, the aim of this work was to optimize the development of a nanoemulsion containing a synthetic chalcone for CL treatment using a 2(2) full factorial design. The formulations were prepared by spontaneous emulsification and the experimental design studied the influence of two independent variables (type of surfactant - soybean lecithin or sorbitan monooleate and type of co-surfactants - polysorbate 20 or polysorbate 80) on the physicochemical characteristics of the nanoemulsions, as well as on the skin permeation/retention of the synthetic chalcone in porcine skin. In order to evaluate the stability of the systems, the antileishmanial assay was performed against Leishmania amazonensis 24 hours and 60 days after the preparation of the nanoemulsions. The formulation composed of soybean lecithin and polysorbate 20 presented suitable physicochemical characteristics (droplet size 171.9 nm; polydispersity index 0.14; zeta potential -39.43 mV; pH 5.16; and viscosity 2.00 cP), drug content (91.09%) and the highest retention in dermis (3.03 ug.g(-1)) - the main response of interest - confirmed by confocal microscopy. This formulation also presented better stability of leishmanicidal activity in vitro against L. amazonensis amastigote forms (half maximal inhibitory concentration value 0.32+/-0.05 uM), which confirmed the potential of the nanoemulsion soybean lecithin and polysorbate 20 for CL treatment. PMID- 26366077 TI - Cross talk between poly(ADP-ribose) polymerase 1 methylation and oxidative stress involved in the toxic effect of anatase titanium dioxide nanoparticles. AB - Given the tremendous growth in the application of titanium dioxide nanoparticles (TNPs), concerns about the potential health hazards of TNPs to humans have been raised. Poly(ADP-ribose) polymerase 1 (PARP-1), a highly conserved DNA-binding protein, is involved in many molecular and cellular processes. Limited data demonstrated that certain nanomaterials induced the aberrant hypermethylation of PARP-1. However, the mechanism involved in TNP-induced PARP-1 abnormal methylation has not been studied. A549 cells were incubated with anatase TNPs (22.1 nm) for 24 hours pretreatment with or without methyltransferase inhibitor 5 aza-2'-deoxycytidine and the reactive oxygen species (ROS) scavenger alpha-lipoic acid to assess the possible role of methylation and ROS in the toxic effect of TNPs. After TNPs characterization, a battery of assays was performed to evaluate the toxic effect of TNPs, PARP-1 methylation status, and oxidative damage. Results showed that TNPs decreased the cell viability in a dose-dependent manner, in accordance with the increase of lactate dehydrogenase activity, which indicated membrane damage of cells. Similar to the high level of PARP-1 methylation, the generation of ROS was significantly increased after exposure to TNPs for 24 hours. Furthermore, alpha-lipoic acid decreased TNP-induced ROS generation and then attenuated TNP-triggered PARP-1 hypermethylation. Meanwhile, 5-aza-2'-deoxycytidine simultaneously decreased the ROS generation induced by TNPs, resulting in the decline of PARP-1 methylation. In summary, TNPs triggered the aberrant hypermethylation of the PARP-1 promoter and there was a cross talk between oxidative stress and PARP-1 methylation in the toxic effect of TNPs. PMID- 26366079 TI - Potential toxicity of dental nanomaterials to the central nervous system. PMID- 26366078 TI - Multi-small molecule conjugations as new targeted delivery carriers for tumor therapy. AB - In response to the challenges of cancer chemotherapeutics, including poor physicochemical properties, low tumor targeting ability, and harmful side effects, we developed a new tumor-targeted multi-small molecule drug delivery platform. Using paclitaxel (PTX) as a model therapeutic, we prepared two prodrugs, ie, folic acid-fluorescein-5(6)-isothiocyanate-arginine-paclitaxel (FA FITC-Arg-PTX) and folic acid-5-aminofluorescein-glutamic-paclitaxel (FA-5AF-Glu PTX), composed of folic acid (FA, target), amino acids (Arg or Glu, linker), and fluorescent dye (fluorescein in vitro or near-infrared fluorescent dye in vivo) in order to better understand the mechanism of PTX prodrug targeting. In vitro and acute toxicity studies demonstrated the low toxicity of the prodrug formulations compared with the free drug. In vitro and in vivo studies indicated that folate receptor-mediated uptake of PTX-conjugated multi-small molecule carriers induced high antitumor activity. Notably, compared with free PTX and with PTX-loaded macromolecular carriers from our previous study, this multi-small molecule-conjugated strategy improved the water solubility, loading rate, targeting ability, antitumor activity, and toxicity profile of PTX. These results support the use of multi-small molecules as tumor-targeting drug delivery systems. PMID- 26366076 TI - Pre- and postmortem imaging of transplanted cells. AB - Therapeutic interventions based on the transplantation of stem and progenitor cells have garnered increasing interest. This interest is fueled by successful preclinical studies for indications in many diseases, including the cardiovascular, central nervous, and musculoskeletal system. Further progress in this field is contingent upon access to techniques that facilitate an unambiguous identification and characterization of grafted cells. Such methods are invaluable for optimization of cell delivery, improvement of cell survival, and assessment of the functional integration of grafted cells. Following is a focused overview of the currently available cell detection and tracking methodologies that covers the entire spectrum from pre- to postmortem cell identification. PMID- 26366080 TI - Nanolayer formation on titanium by phosphonated gelatin for cell adhesion and growth enhancement. AB - Phosphonated gelatin was prepared for surface modification of titanium to stimulate cell functions. The modified gelatin was synthesized by coupling with 3 aminopropylphosphonic acid using water-soluble carbodiimide and characterized by (31)P nuclear magnetic resonance and gel permeation chromatography. Circular dichroism revealed no differences in the conformations of unmodified and phosphonated gelatin. However, the gelation temperature was changed by the modification. Even a high concentration of modified gelatin did not form a gel at room temperature. Time-of-flight secondary ion mass spectrometry showed direct bonding between the phosphonated gelatin and the titanium surface after binding. The binding behavior of phosphonated gelatin on the titanium surface was quantitatively analyzed by a quartz crystal microbalance. Ellipsometry showed the formation of a several nanometer layer of gelatin on the surface. Contact angle measurement indicated that the modified titanium surface was hydrophobic. Enhancement of the attachment and spreading of MC-3T3L1 osteoblastic cells was observed on the phosphonated gelatin-modified titanium. These effects on cell adhesion also led to growth enhancement. Phosphonation of gelatin was effective for preparation of a cell-stimulating titanium surface. PMID- 26366082 TI - Cationic polyelectrolyte-mediated delivery of antisense morpholino oligonucleotides for exon-skipping in vitro and in mdx mice. AB - In this study, we investigated a series of cationic polyelectrolytes (PEs) with different size and composition for their potential to improve delivery of an antisense phosphorodiamidate morpholino oligomer (PMO) both in vitro and in vivo. The results showed that the poly(diallyldimethylammonium chloride) (PDDAC) polymer series, especially PE-3 and PE-4, improves the delivery efficiency of PMO, comparable with Endoporter-mediated PMO delivery in vitro. The enhanced PMO delivery and targeting to dystrophin exon 23 was further observed in mdx mice, up to fourfold with the PE-4, compared with PMO alone. The cytotoxicity of the PEs was lower than that of Endoporter and polyethylenimine 25,000 Da in vitro, and was not clearly detected in muscle in vivo under the tested concentrations. Together, these results demonstrate that optimization of PE molecular size, composition, and distribution of cationic charge are key factors to achieve enhanced PMO exon-skipping efficiency. The increased efficiency and lower toxicity show this PDDAC series to be capable gene/antisense oligonucleotide delivery-enhancing agents for treating muscular dystrophy and other diseases. PMID- 26366081 TI - Inorganic nanolayers: structure, preparation, and biomedical applications. AB - Hydrotalcite-like compounds are two-dimensional inorganic nanolayers also known as clay minerals or anionic clays or layered double hydroxides/layered hydroxy salts, and have emerged as a single type of material with numerous biomedical applications, such as drug delivery, gene delivery, cosmetics, and biosensing. Inorganic nanolayers are promising materials due to their fascinating properties, such as ease of preparation, ability to intercalate different type of anions (inorganic, organic, biomolecules, and even genes), high thermal stability, delivery of intercalated anions in a sustained manner, high biocompatibility, and easy biodegradation. Inorganic nanolayers have been the focus for researchers over the last decade, resulting in widening application horizons, especially in the field of biomedical science. These nanolayers have been widely applied in drug and gene delivery. They have also been applied in biosensing technology, and most recently in bioimaging science. The suitability of inorganic nanolayers for application in drug delivery, gene delivery, biosensing technology, and bioimaging science makes them ideal materials to be applied for theranostic purposes. In this paper, we review the structure, methods of preparation, and latest advances made by inorganic nanolayers in such biomedical applications as drug delivery, gene delivery, biosensing, and bioimaging. PMID- 26366084 TI - Efficacy and tolerability of aripiprazole once monthly for schizophrenia: a systematic review and meta-analysis of randomized controlled trials. AB - OBJECTIVE: We conducted a systematic review and meta-analysis of the efficacy of aripiprazole once monthly (AOM) for schizophrenia. METHODS: Randomized controlled trials (RCTs) on AOM, published until June 25, 2015, were retrieved from PubMed, Cochrane, and PsycINFO databases. Relative risk (RR), standardized mean difference (SMD), 95% confidence intervals (95% CIs), and numbers needed to treat/harm (NNT/NNH) were calculated. RESULTS: We identified four relevant RCTs (total n=1,860), two placebo-controlled trials, one noninferiority trial comparing AOM to oral aripiprazole (OA), and one including therapeutic doses of AOM and OA, as well as an AOM dose below therapeutic threshold (control arm). AOM was superior to placebo for decreasing Positive and Negative Syndrome Scale (PANSS) total scores (SMD =-0.65, 95% CI =-0.90 to -0.41, n=1,126). However, PANSS total scores did not differ significantly between pooled AOM and OA groups. The pooled AOM group showed significantly lower incidence of all-cause discontinuation (RR =0.54, 95% CI =0.41-0.71, n=1,139, NNH =4) and inefficacy (RR =0.28, 95% CI =0.21-0.38, n=1,139, NNH =5) than placebo, but was not superior to placebo regarding discontinuation due to adverse events (AEs) or death. The AOM group exhibited a lower incidence of all-cause discontinuation than OA (RR =0.78, 95% CI =0.64-0.95, n=986, NNH =14), but there were no intergroup differences in discontinuation due to inefficacy, AEs, or death. There were no significant differences in extrapyramidal symptoms scale scores between AOM and placebo or between AOM and OA. AOM resulted in higher weight gain than placebo (SMD =0.41, 95% CI =0.18-0.64, n=734) but lower than OA (SMD =-0.16, 95% CI =-0.29 to -0.02, n=847). CONCLUSION: AOM has antipsychotic efficacy and low risk of discontinuation due to AEs. PMID- 26366083 TI - The effectiveness of racket-sport intervention on visual perception and executive functions in children with mild intellectual disabilities and borderline intellectual functioning. AB - BACKGROUND: This study aimed to investigate the effects of table tennis training (TTT) versus standard occupational therapy (SOT) on visual perception and executive functions in school-age children with mild intellectual disabilities and borderline intellectual functioning. SUBJECTS AND METHODS: Children (n=91) were randomly assigned to intervention with either SOT (n=46, 20 females, mean age =10.9+/-3.9 years) or TTT (n=45, 21 females, mean age =10.6+/-3.6 years), while another 41 (18 females, mean age =10.7+/-4.0 years) served as controls. Both the SOT and TTT programs were administered 60 minutes per session, three times a week, for 16 weeks. The Test of Visual Perceptual Skill-third edition (TVPS-3) was used to evaluate visual perception, and executive functions were assessed by the Wisconsin Card Sorting Test 64-card version (WCST-64) and the Stroop test. RESULTS: At postintervention, the two intervention groups significantly outperformed the control group on all measures of visual perception and executive functions. Participants in the TTT group had significantly greater before-after changes on all measures of the TVPS-3, WCST-64, and the Stroop test compared to the SOT and controls. CONCLUSION: Table tennis could be considered a therapy option while treating cognitive/perceptual problems in children with mild intellectual disabilities and borderline intellectual functioning. Implications for clinical professionals and recommendations for further research are discussed. PMID- 26366085 TI - Efficacy of biological agents administered as monotherapy in rheumatoid arthritis: a Bayesian mixed-treatment comparison analysis. AB - BACKGROUND: Biological agents provide an important therapeutic alternative for rheumatoid arthritis patients refractory to conventional disease-modifying antirheumatic drugs. Few head-to-head comparative trials are available. PURPOSE: The aim of this meta-analysis was to compare the relative efficacy of different biologic agents indicated for use as monotherapy in rheumatoid arthritis. METHODS: A systemic literature search was performed on electronic databases to identify articles reporting double-blind randomized controlled trials investigating the efficacy of biologic agents indicated for monotherapy. Efficacy was assessed using American College of Rheumatology (ACR) 20, 50, and 70 criteria at 16-24 weeks. Relative efficacy was estimated using Bayesian mixed-treatment comparison models. Outcome measures were expressed as odds ratio and 95% credible intervals. RESULTS: Ten randomized controlled trials were selected for data extraction and analysis. Mixed-treatment comparison analysis revealed that tocilizumab offered 100% probability of being the best treatment for inducing an ACR20 response versus placebo, methotrexate, adalimumab, or etanercept. Likewise, for ACR50 and ACR70 outcome responses, tocilizumab had a 99.8% or 98.7% probability of being the best treatment, respectively, compared to other treatments or placebo. Tocilizumab increased the relative probability of being the best treatment (vs methotrexate) by 3.2-fold (odds ratio: 2.1-3.89) for all ACR outcomes. CONCLUSION: Tocilizumab offered the greatest possibility of obtaining an ACR20, ACR50, and ACR70 outcome vs other monotherapies or placebo. PMID- 26366086 TI - The role of SDF-1/CXCR4 in the vasculogenesis and remodeling of cerebral arteriovenous malformation. AB - BACKGROUND: Cerebral arteriovenous malformation (AVM) involves the vasculogenesis of cerebral blood vessels and can cause severe intracranial hemorrhage. Stromal cell-derived factor-1 (SDF-1) and its receptor, CXCR4, are believed to exert multiple physiological functions including angiogenesis. Thus, we investigated the role of SDF-1/CXCR4 in the vasculogenesis of cerebral AVM. METHODS: Brain AVM lesions from surgical resections were analyzed for the expression of SDF-1, CXCR4, VEGF-A, and HIF-1 by using immunohistochemical staining. Flow cytometry was used to quantify the level of circulating endothelial progenitor cells (EPCs). Further, in an animal study, chronic cerebral hypoperfusion model rats were analyzed for the expression of SDF-1 and HIF-1. CXCR4 antagonist, AMD3100, was also used to detect its effects on cerebral vasculogenesis and SDF-1 expression. RESULTS: Large amounts of CXCR4-positive CD45(+) cells were found in brain AVM lesion blood vessel walls, which also have higher SDF-1 expression. Cerebral AVM patients also had higher level of EPCs and SDF-1. In chronic cerebral hypoperfusion rats, SDF-1, HIF-1, and CD45 expressions were elevated. The application of AMD3100 effectively suppressed angiogenesis and infiltration of CXCR4-positive CD45(+) cells in hypoperfusion rats compared to controls. CONCLUSION: The SDF-1/CXCR4 axis plays an important role in the vasculogenesis and migration of inflammatory cells in cerebral AVM lesions, possibly via the recruitment of bone marrow EPCs. PMID- 26366087 TI - Efficacy and safety of metformin or oral contraceptives, or both in polycystic ovary syndrome. AB - BACKGROUND: Polycystic ovary syndrome (PCOS) is an endocrinopathy that affects approximately 10% of reproductive-aged women throughout their lives. Women with PCOS present with heterogeneous symptoms including ovulatory dysfunction, hyperandrogenism, and polycystic ovaries. Therefore, lifelong individualized management should be considered. Pharmacological agents commonly used to manage the symptoms are metformin and oral contraceptive pills. Although these medications have been beneficial in treating PCOS symptoms, their efficacy and safety are still not entirely elucidated. This study aimed to report the efficacy and safety of metformin, oral contraceptives, or their combination in the treatment of PCOS and to define their specific individual roles. METHODS: A literature search of original studies published in PubMed and Scopus was conducted to identify studies comparing metformin with oral contraceptives or evaluating the combination of both in PCOS. RESULTS: Eight clinical trials involving 313 patients were examined in the review. The intervention dosage of metformin ranged from 1,000 to 2,000 mg/d and that of oral contraceptives was ethinylestradiol 35 ug and cyproterone acetate 2 mg. Lower body mass index was observed with regimens including metformin, but increased body mass index was observed in monotherapy with oral contraceptives. Administration of metformin or oral contraceptives, especially as monotherapy, had a negative effect on lipid profiles. In addition, there are still uncertainties surrounding the effects of metformin or oral contraceptives in the management of insulin level, although they improved total testosterone and sex hormone-binding globulin levels. In the included studies, significant side effects due to metformin or oral contraceptives were not reported. CONCLUSION: The clinical trials suggest that metformin or oral contraceptives are at least patient convenient, efficacious, and safe for the treatment of PCOS. However, well-designed, prospective, long term, large-scale, randomized clinical trials are necessary to elucidate the efficacy and safety of metformin, oral contraceptives, or both in the treatment of PCOS, and to elucidate their individual roles in the treatment of this condition. PMID- 26366088 TI - Comparing withdrawal and non-withdrawal of life-sustaining treatment among patients who died from stroke. AB - BACKGROUND: In severe stroke, a decision to withdraw life-sustaining treatment is sometimes made in cooperation with the family. The aim of this study was to study the time from withdrawing life-sustaining treatment to death in patients with severe ischemic or hemorrhagic stroke. METHODS: In total, 2,506 patients with stroke admitted to Haukeland University Hospital between 2006 and 2011 were prospectively registered in the Bergen NORSTROKE database. Risk factors, stroke severity, etiology, and blood analyses were registered. Retrospectively, the patients' records were examined to determine the number of days from withdrawing all life-sustaining treatment to death in patients who died from severe stroke during the hospital stay. RESULTS: Life-sustaining treatment was withheld in 50 patients with severe stroke. Median time to death after withdrawing life sustaining treatment was 4 days, and a quarter lived at least 1 week (range =1-11 days). Cox regression analyses showed that short time from withdrawing life sustaining treatment to death was associated with high age (Hazard ratio [HR] =1.05, P=0.07), male sex (HR =2.9, P=0.01), high C-reactive protein on admission (HR =1.01, P=0.001), and hemorrhagic stroke (versus ischemic stroke, HR =1.5, P=0.03). CONCLUSION: One week after withdrawing life-sustaining treatment, a quarter of our patients with severe stroke remained alive. Short time to death was associated with high age, male sex, hemorrhagic stroke, and high C-reactive protein on admittance. PMID- 26366089 TI - Clinical and prognostic significance of pathological and inflammatory markers in the surgical treatment of locally advanced colorectal cancer. AB - BACKGROUND: Locally advanced colorectal cancer (CRC) may vary in its clinical and pathological appearance. It is now accepted that progression of disease in patients with locally advanced CRC is determined not only by local tumor characteristics but also by the immune system and inflammatory response in the body. METHODS: We investigated patients with confirmed CRC who were treated in the surgical clinic at the University Hospital Alexandrovska over a 10-year period and retrospectively evaluated the histological features of the preoperative biopsies and operative specimens removed during radical multivisceral resections. We also collected prospective data for serum C-reactive protein levels and Jass-Klintrup score, Petersen Index score, and Glasgow Prognostic Score in patients with locally advanced CRC. RESULTS: Of 1,105 patients with CRC, 327 (29.6%) were diagnosed with locally advanced disease. In total, 108 combined multivisceral resections (79 for primary tumors and 29 for recurrent tumors) were performed. Overall survival was 34 months for pR0 cases and 12 months for pR1 cases (P<0.05). Our data confirmed that C-reactive protein is a prognostic marker of overall survival. Data for 48 patients with histologically confirmed locally advanced tumors showed significantly increased survival with a higher Jass-Klintrup score (P=0.037). In patients with node negative disease, 5-year survival was 49%. However, where there were high-risk pathological characteristics according to the Petersen Index, survival was similar to that for node-positive disease (P=0.702). Our data also showed a significant difference in survival between groups divided according to whether they had a modified Glasgow Prognostic Score of 1 or 2 (P=0.031). CONCLUSION: In order to maintain a reasonable balance between an aggressive approach and so called meaningless "surgical exorbitance", we should focus on certain histopathological and inflammatory markers that can be identified as additional factors for planning the type and volume of surgical treatment. PMID- 26366090 TI - Apoptotic effect of cordycepin combined with cisplatin and/or paclitaxel on MA-10 mouse Leydig tumor cells. AB - BACKGROUND: Chemotherapy is not limited to a single treatment, and the evidence demonstrates that different drug combinations can have positive results in patients. In this study, we sought to determine whether cordycepin combined with cisplatin and/or paclitaxel would have an additive effective on inducing apoptosis in mouse Leydig tumor cells, and the mechanisms were also briefly examined. METHODS: The additive effects of cordycepin combined with cisplatin and/or paclitaxel on apoptosis in MA-10 cells were investigated by monitoring changes in morphological characteristics and examining cell viability, flow cytometry assays, and Western blot analyses. RESULTS: Combination of cordycepin plus cisplatin and/or paclitaxel for 12 and 24 hours induced apoptotic features in MA-10 cells. The MTT assay showed that the combination treatment reduced the viability of MA-10 cells in a dose-dependent manner, with additive effects. Cell cycle analysis showed that combination treatment significantly increased subG1 phase cell numbers in MA-10 cells, indicating apoptosis. Moreover, cordycepin plus cisplatin and/or paclitaxel significantly induced cleavage of caspase-8, caspase-9, caspase-3, and poly ADP-ribose polymerase, and phosphorylation of c Jun NH2-terminal kinase, extracellular signal-regulated kinase, p38, and p53 proteins in MA-10 cells. CONCLUSION: Cordycepin plus cisplatin and/or paclitaxel can have an additive effect on apoptosis in MA-10 cells, with activation of caspase, mitogen-activated protein kinase, and p53 signal pathways. PMID- 26366091 TI - The impact of histological types on the efficacy of angiogenesis inhibitors in the treatment of advanced NSCLC: a meta-analysis of randomized controlled trials. AB - PURPOSE: We aimed at assessing the overall efficacy of angiogenesis inhibitor (AI)-containing regimens in the treatment of advanced non-small-cell lung cancer (NSCLC) according to histological types. METHODS: Studies from PubMed and Web of Science, and abstracts presented at American Society of Clinical Oncology (ASCO) meeting up to October 31, 2014 were searched to identify relevant studies. Eligible studies included prospective randomized controlled trials (RCTs) evaluating AIs in advanced NSCLC with survival data according to patients' histologies. The endpoints were overall survival (OS) and progression-free survival (PFS). Statistical analyses were conducted by using either random effects or fixed effect models according to the heterogeneity of included studies. RESULTS: A total of 10,035 patients with advanced NSCLC from 13 RCTs were identified for analysis. The pooled results demonstrated that AI-containing regimens significantly improved the PFS (HR, 0.84, 95% confidence interval (CI): 0.78-0.91, P<0.001) and OS (HR, 0.92, 95% CI: 0.85-0.99, P=0.017) in lung adenocarcinoma when compared to non-AI-containing regimens. Additionally, there was a significantly improved PFS (HR, 0.87, 95% CI: 0.77-0.98, P=0.027) for AI containing regimens in squamous cell lung carcinoma, but it did not translated into OS benefit (HR, 1.02, 95% CI: 0.92-1.15, P=0.68). For NSCLC patients with other histological types, the use of AIs did not significantly improve PFS (HR, 0.90, 95% CI: 0.75-1.09, P=0.27) and OS (HR, 0.90, 95% CI: 0.76-1.08, P=0.19). CONCLUSION: The findings of this study suggest that the addition of AIs to the treatment therapies for patients with lung adenocarcinoma offers improved survival benefits. Prospective clinical trials investigating the role of AIs in this setting are recommended. PMID- 26366092 TI - Chronic neutrophilic leukemia: a clinical perspective. AB - Chronic neutrophilic leukemia (CNL) is a rare myeloproliferative neoplasm (MPN) that includes only 150 patients described to date meeting the latest World Health Organization (WHO) criteria and the recently reported CSF3R mutations. The diagnosis is based on morphological criteria of granulocytic cells and the exclusion of genetic drivers that are known to occur in others MPNs, such as BCR ABL1, PDGFRA/B, or FGFR1 rearrangements. However, this scenario changed with the identification of oncogenic mutations in the CSF3R gene in approximately 83% of WHO-defined and no monoclonal gammopathy-associated CNL patients. CSF3R T618I is a highly specific molecular marker for CNL that is sensitive to inhibition in vitro and in vivo by currently approved protein kinase inhibitors. In addition to CSF3R mutations, other genetic alterations have been found, notably mutations in SETBP1, which may be used as prognostic markers to guide therapeutic decisions. These findings will help to understand the pathogenesis of CNL and greatly impact the clinical management of this disease. In this review, we discuss the new genetic alterations recently found in CNL and the clinical perspectives in its diagnosis and treatment. Fortunately, since the diagnosis of CNL is not based on exclusion anymore, the molecular characterization of the CSF3R gene must be included in the WHO criteria for CNL diagnosis. PMID- 26366093 TI - Profile of obinutuzumab for the treatment of patients with previously untreated chronic lymphocytic leukemia. AB - Chronic lymphocytic leukemia (CLL) is a hematologic malignancy derived from a clonal population of mature B-lymphocytes characterized by relatively low CD20 antigen expression. Although the disease often takes an indolent course, the majority of patients will eventually require therapy. Standard treatment for medically fit patients includes purine analogs and/or alkylating agents in addition to the type I anti-CD20 monoclonal antibody, rituximab. This therapy is inherently myelosuppressive and can result in significant morbidity and even mortality in patients with impaired performance status due to age and/or medical comorbidities. Historically, treatment options for the elderly or frail patient population were limited to mono-therapy with the oral alkylating agent, chlorambucil, rituximab, or another type I anti-CD20 monoclonal antibody ofatumumab. Recently, a newer-generation anti-CD20 monoclonal antibody, obinutuzumab, was developed for patients with CLL. Obinutuzumab is a humanized type II monoclonal antibody that appears to have more direct antibody-dependent cell-mediated cytotoxicity (ADCC) and possibly more direct cytotoxicity in vitro than previously available type I antibodies. A large Phase III prospective randomized clinical trial for older patients with impaired renal function and/or significant medical comorbidities demonstrated that when compared to conventionally-dosed rituximab and chlorambucil, the combination of chlorambucil and obinutuzumab administered at a dose and schedule involving early loading doses improved response rates and progression-free survival without significantly increasing toxicity. Results of this pivotal trial led to the FDA (US Food and Drug Administration) approval of obinutuzumab in combination with chlorambucil for frontline treatment of CLL. Obinutuzumab expands the armamentarium of active and less-toxic targeted agents in the evolving treatment landscape of CLL, providing physicians and patients with an additional therapeutic option. PMID- 26366094 TI - The distinctive nature of adenocarcinoma of the lung. AB - In recent years, many personalized treatments have been developed for NSCLC (non small-cell lung cancer) patients. Among these, gefitinib, erlotinib, and afatinib are selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors for patients with EGFR gene mutations, while crizotinib and ceritinib are two new tyrosine kinase inhibitors directed against the echinoderm microtubule-like protein 4-anaplastic lymphoma kinase translocation. The possibility of these new molecules being used to treat patients without adenocarcinoma histology is notably small. For example, EGFR mutations and anaplastic lymphoma kinase fusion gene rearrangement are rare in patients with squamous cell carcinoma (generally <1%). Additionally, the benefit of targeted treatment approaches in patients with small-cell lung cancer histology is limited. All of these findings highlight the distinctive nature of adenocarcinoma of the lung among all lung cancer subtypes. Unfortunately, to date, less than 15% of patients with adenocarcinoma of the lung are ideal candidates for these targeted therapies. PMID- 26366095 TI - Bevacizumab plus chemotherapy as third- or later-line therapy in patients with heavily treated metastatic colorectal cancer. AB - BACKGROUND: Currently available third- or later-line therapy for metastatic colorectal cancer (mCRC) is limited in its efficacy, with a weak survival benefit in patients who progressed after two or more lines of standard therapy. Our retrospective study aimed to explore the value of bevacizumab plus chemotherapy in this setting. METHODS: Patients with mCRC who received fluoropyrimidine, oxaliplatin, and irinotecan as first- and second-line chemotherapy were selected for inclusion. Treatment consisted of bevacizumab plus chemotherapy. Chemotherapy consisted mainly of oxaliplatin, irinotecan, and fluoropyrimidine. RESULTS: Between February 2010 and December 2012, 35 consecutive patients with mCRC were treated with bevacizumab plus chemotherapy as a third- or later-line treatment. No complete responses, seven partial responses (20%), 22 stable disease responses (62.9%), and six progressive disease responses (17.1%) were obtained, producing an objective response rate of 20% and a disease control rate of 82.9%. With a median follow-up of 11.3 months (range: 0.7-48.0 months), the median progression free survival was 5.98 months (95% confidence interval: 4.76-7.2 months), and the median overall survival was 14.77 months (95% confidence interval: 11.45-18.1 months). In the univariate analysis, patients with a primary colon tumor might have had a longer overall survival than patients with a primary rectal tumor (18.8 months vs 11.1 months, respectively; P=0.037). Common chemotherapy-related toxicities were nausea/vomiting (48.6%), fatigue (34.3%), leucopenia (40%), neutropenia, (42.9%), and anemia (42.9%), with one patient with grade 3 neutropenia, and two patients with grade 3 thrombocytopenia. The common bevacizumab-associated toxicity was hypertension (31.4%). None of the patients discontinued therapy or died because of bevacizumab-associated toxicities. CONCLUSION: Our data showed that adding bevacizumab to third- or later-line therapy might lead to tumor control and improved survival in heavily pretreated mCRC patients. In addition, preliminary data suggested that primary colon cancer was more likely to benefit from bevacizumab-containing regimens. Toxicities were acceptable, and no new toxicity was identified. Further studies are needed to validate these findings. PMID- 26366096 TI - Dietary fiber, whole grains, carbohydrate, glycemic index, and glycemic load in relation to risk of prostate cancer. AB - BACKGROUND: The relationships between dietary fiber, whole grains, carbohydrate, glycemic index (GI), glycemic load (GL), and prostate cancer risk are unclear. We conducted a systematic review and meta-analysis to investigate these associations. METHODS: Relevant studies were identified by a search of PubMed database and EMBASE database up to April 2015. A random effects model was used to calculate the summary relative risks (RRs) and their corresponding 95% confidence intervals (CIs). RESULTS: Twenty-seven epidemiological studies (18 case-control studies and nine cohort studies) were included in the final analysis. The pooled RRs of prostate cancer were 0.94 (95% CI 0.85-1.05, P=0.285), 1.13 (95% CI 0.98 1.30, P=0.095), 0.96 (95% CI 0.81-1.14, P=0.672), 1.06 (95% CI 0.96-1.18, P=0.254), and 1.04 (95% CI 0.91-1.18, P=0.590) for dietary fiber, whole grains, carbohydrate, GI, and GL, respectively. There was no evidence of significant publication bias based on the Begg's test and Egger's test. CONCLUSION: The findings of this meta-analysis indicate that, based on available information, dietary fiber, whole grains, carbohydrate, GI, and GL are not associated with the risk of prostate cancer. PMID- 26366097 TI - The expression of the PI3K/AKT/mTOR pathway in gastric cancer and its role in gastric cancer prognosis. AB - OBJECTIVE: To analyze the correlation between sequential aspects of the phosphoinositide-3 kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway by immunohistochemistry in the primary lesion of gastric cancer, clinicopathologic factors, and survival in Chinese patients to explore the role of sequential analysis of multiple targets in prognoses. METHODS: Immunohistochemistry was performed to examine the expression of PI3K, phosphorylated-AKT (p-AKT), and phosphorylated-mTOR (p-mTOR) in 59 primary lesion samples ranging from Stages I to IV after gastrectomy. The correlation between sequential expression of multiple targets, and clinicopathologic factors and survival was analyzed. RESULTS: The positive expression rates of PI3K, p-AKT, and p-mTOR were 49%, 58%, and 56%, respectively. There were eleven cases with three biomarkers positive (19%), 22 cases with two biomarkers positive (37%), and 19 cases with only one biomarker positive (32%). Seven cases (12%) were all negative. Multi-factorial Cox regression analysis showed that neural invasion, vascular invasion, size of the tumor, lymph nodes affected, metastasis, carbohydrate antigen 19-9 level, and PI3K/p-AKT/p-mTOR simultaneous expression were independent prognostic parameters. The risk of death for the cases with two biomarkers positive was 0.367 times that for the cases with three biomarkers positive (P=0.166). The risk of death for the cases with only one biomarker positive was 0.105 times that for the cases with three biomarkers positive (P=0.058). The risk of death for the cases with three biomarkers negative was 0.017 times that for the cases with three biomarkers positive (P=0.022). CONCLUSION: Our study generated the hypothesis that patients with gastric cancer with simultaneous expression of PI3K/p-AKT/p-mTOR had worse outcome. But we need more rigorous validation in a larger data set. PMID- 26366098 TI - Treatment compliance and severe adverse events limit the use of tyrosine kinase inhibitors in refractory thyroid cancer. AB - OBJECTIVE: The aim of the present study was to assess patient compliance with tyrosine kinase inhibitor (TKI) treatment used for refractory and progressive thyroid cancer, in addition to the efficacy and serious adverse events associated with these agents. METHODS: We retrospectively analyzed data from adult patients with metastatic differentiated or medullary thyroid cancer unresponsive to conventional treatment and treated with TKIs. Patients received treatment until disease progression or onset of serious adverse events, or until they expressed an intention to stop treatment. RESULTS: Twenty-four patients received TKIs. The median duration of treatment was four (range: 1-19) cycles. The most frequent adverse events were fatigue, nausea, diarrhea, hypertension, and stomatitis, and the most severe were nasal bleeding, diarrhea, heart failure, rhabdomyolysis, renal failure, QT prolongation, neutropenia, and severe fatigue. Dose reduction was required in eight patients, while five decided to terminate TKI therapy because adverse events impaired their everyday activities. During therapy, two patients showed a partial response and three showed stable disease. The lungs were the metastatic sites favoring a response to treatment. CONCLUSION: Patient selection and meticulous pretreatment education are necessary in order to ensure adherence with TKI therapy. If adverse events appear, dose reduction or temporary treatment interruption may be offered because some adverse events resolve with continuation of treatment. In the event of serious adverse events, treatment discontinuation is necessary. PMID- 26366099 TI - Acceptance of health technology assessment submissions with incremental cost effectiveness ratios above the cost-effectiveness threshold. AB - OBJECTIVES: In health technology assessment (HTA) agencies where cost effectiveness plays a role in decision-making, an incremental cost-effectiveness ratio (ICER) threshold is often used to inform reimbursement decisions. The acceptance of submissions with ICERs higher than the threshold was assessed across different agencies and across indications, in order to inform future reimbursement submissions. METHODS: All HTA appraisals from May 2000 to May 2014 from National Institute for Health and Care Excellence (NICE), Scottish Medicines Consortium (SMC), Pharmaceutical Benefits Advisory Committee (PBAC), and Canadian Agency for Drugs and Technologies in Health (CADTH) were assessed. Multiple technology appraisals, resubmissions, vaccination programs, and requests for advice were excluded. Submissions not reporting an ICER, or for which an ICER could not be determined were also excluded. The remaining appraisals were reviewed, and the submitted ICER, recommendation, and reasoning behind the recommendation were extracted. RESULTS: NICE recommended the highest proportion of submissions with ICERs higher than the threshold (34% accepted without restrictions; 20% with restrictions), followed by PBAC (16% accepted without restrictions; 4% with restrictions), SMC (11% accepted without restrictions; 14% accepted with restrictions), and CADTH (0% accepted without restrictions; 26% with restrictions). Overall, the majority of higher-than-threshold ICER submissions were classified into the "malignant disease and immunosuppression" therapeutic category; however, there was no notable variation in acceptance rates by disease area. Reasons for accepting submissions reporting ICERs above the threshold included high clinical benefit over the standard of care, and addressing an unmet therapeutic need. CONCLUSION: Acceptance of submissions with higher-than-threshold ICERs varied by HTA agency and was not significantly influenced by disease category. Such submissions must be accompanied by robust, concrete, and transparent evidence in order to achieve patient access. PMID- 26366101 TI - The role of vitamin C in pushing back the boundaries of skin aging: an ultrasonographic approach. AB - BACKGROUND: Imagistic methods stand as modern, non-invasive, and objective means of assessing the impact of topical cutaneous therapies. OBJECTIVE: This study focuses on the evaluation, by high-frequency ultrasound, of the cutaneous changes induced by topical use of a vitamin C complex at facial level. METHODS: A vitamin C-based solution/Placebo moisturizer cream was applied at facial level of 60 healthy female subjects according to a predetermined protocol. Ultrasonographic images (Dermascan C, 20 MHz) were taken from zygomatic level initially, at 40 and 60 days after therapy. The following parameters were assessed for every subject: thickness of the epidermis and dermis (mm), the number of low (LEP), medium (MEP), high echogenic pixels (HEP), and the number of LEP in the upper dermis/lower dermis (LEPs/LEPi). RESULTS: LEP decreased significantly in all age categories during and after therapy, but especially in the first 2 age intervals, up to the age of 50 (P=0.0001). MEP and HEP, pixel categories that quantify protein synthesis also had an age-dependent evolution in the study, increasing significantly in all age categories but most of all in the first age interval (P=0.002). Our ultrasonographic data suggest that collagen synthesis increased significantly after topical vitamin C therapy, and is responsible for the increase in MEP and HEP and consequent decrease of the LEP. CONCLUSION: Our study shows that topically applied vitamin C is highly efficient as a rejuvenation therapy, inducing significant collagen synthesis in all age groups with minimal side effects. PMID- 26366100 TI - Current perspectives on the health risks associated with the consumption of advanced glycation end products: recommendations for dietary management. AB - Advanced glycation end products (AGEs) constitute a complex group of compounds produced endogenously during the aging process and under conditions of hyperglycemia and oxidative stress. AGEs also have an emerging exogenous origin. Cigarette smoke and diet are the two main exogenous sources of AGEs (glycotoxins). Modern Western diets are rich in AGEs which have been implicated in the pathogenesis of several metabolic and degenerative disorders. Accumulating evidence underlies the beneficial effect of the dietary restriction of AGEs not only in animal studies but also in patients with diabetic complications and metabolic diseases. This article reviews the evidence linking dietary glycotoxins to several disorders from diabetic complications and renal failure to liver dysfunction, female reproduction, eye and cognitive disorders as well as cancer. Furthermore, strategies for AGE reduction are discussed with a focus on dietary modification. PMID- 26366102 TI - Facial primer provides immediate and long-term improvements in mild-to-moderate facial hyperpigmentation and fine lines associated with photoaging. AB - BACKGROUND: Photoaged skin results from various environmental factors, most importantly chronic sun exposure. Dyschromia and fine lines/wrinkles are common clinical manifestations of photodamaged skin. PURPOSE: This single-center clinical trial was conducted to assess the efficacy and tolerability of a new multifunctional facial primer (camouflage, broad-spectrum SPF 50, and a treatment for hyperpigmentation) when used by females with mild-to-moderate facial hyperpigmentation and fine lines due to photoaging over a course of 12 weeks. PATIENTS AND METHODS: Subjects were provided test material (Even Up-Clinical Pigment Perfector) and supporting products to use on their face and neck. Products were used according to specific application instructions. Clinical grading for efficacy and tolerability assessments were performed by an expert grader at baseline, baseline (post-application primer), week 4, week 8, week 12, and week 12 (post-application primer). Standardized digital photographs were taken, and self-assessment questionnaires were conducted. RESULTS: Twenty-eight female subjects completed the 12-week trial. The facial primer improved scores for the appearance of hyperpigmentation and other photoaging parameters immediately after the first application. The treatment also showed a progressive improvement in the clinical assessment of hyperpigmentation and other photoaging parameters over the 12-week trial. These long-term benefits can be attributed to an improvement in the underlying skin condition. The facial primer was well tolerated. Subject questionnaires showed that the product was highly rated at all visits. CONCLUSION: The facial primer was shown to be effective and well tolerated for immediate and long-term improvement in the appearance of mild-to moderate hyperpigmentation and fine lines associated with photodamage when used over a 12-week period. PMID- 26366104 TI - Predictors of quality of life in patients with end-stage renal disease on hemodialysis. AB - BACKGROUND: Assessment of quality of life (QOL) of end-stage renal disease (ESRD) patients (physical, mental, and social well-being) has become an essential tool to develop better plans of care. Objective of this study is to determine which demographic and biochemical parameters correlate with the QOL scores in patients with ESRD on hemodialysis (HD) using Kidney Disease QOL-36 surveys (KDQOL). METHODS: A retrospective chart review of all ESRD patients who underwent HD at an outpatient center. The five components of the KDQOL were the primary end points of this study (burden of kidney disease, symptoms and problems, effects of kidney disease on daily life, mental component survey, and physical component survey). Scores were grouped into three categories (below average, average, and above average). In addition to demographics (age, sex, and race), the independent variables such as weight gain, number of years on dialysis, urea reduction ratio, calcium, phosphorus, parathyroid hormone, albumin, and hemoglobin in the serum were collected. Chi-square analysis for dependent variables and the nominal independent variables was used, and analysis of variance analysis was used for continuous independent variables. Ordinal regression using PLUM (polytomous universal model) method was used to weigh out possible effects of confounders. RESULTS: The cohort size was 111 patients. Mean age was 61.8 (+/-15.5) years; there were more males than females (64.9% vs 35.1%), the mean time-on-dialysis at the time of the study was 4.3 (4.8) years. Approximately two-thirds of the responses on all five domains of the questionnaire ranked average when compared to the national numbers. The remainders were split between above average (20.6%) and below average (13.4%). In our cohort, no relationships were statistically significant between the five dependent variables of interest and the independent variables by chi-square- and t-test analyses. This was further confirmed by regression analysis. Of note, sex carried the strongest statistical significance (with a P-value of 0.16) as a predictor of "the burden of kidney disease on daily life" in ordinal regression. CONCLUSION: Prior studies have shown variables such as serum phosphate level, intradialytic weight gain, and dialysis adequacy are associated with lower KDQOL scores; however, this was not evident in our analysis likely due to smaller sample size. Larger size studies are required to better understand the predictors of QOL in ESRD patients on HD. PMID- 26366103 TI - An update of clinical management of acute intermittent porphyria. AB - Acute intermittent porphyria (AIP) is due to a deficiency of the third enzyme, the hydroxymethylbilane synthase, in heme biosynthesis. It manifests with occasional neuropsychiatric crises associated with overproduction of porphyrin precursors, aminolevulinic acid and porphobilinogen. The clinical criteria of an acute attack include the paroxysmal nature and various combinations of symptoms, such as abdominal pain, autonomic dysfunction, hyponatremia, muscle weakness, or mental symptoms, in the absence of other obvious causes. Intensive abdominal pain without peritoneal signs, acute peripheral neuropathy, and encephalopathy usually with seizures or psychosis are the key symptoms indicating possible acute porphyria. More than fivefold elevation of urinary porphobilinogen excretion together with typical symptoms of an acute attack is sufficient to start a treatment. Currently, the prognosis of the patients with AIP is good, but physicians should be aware of a potentially fatal outcome of the disease. Mutation screening and identification of type of acute porphyria can be done at the quiescent phase of the disease. The management of patients with AIP include following strategies: A, during an acute attack: 1) treatment with heme preparations, if an acute attack is severe or moderate; 2) symptomatic treatment of autonomic dysfunctions, polyneuropathy and encephalopathy; 3) exclusion of precipitating factors; and 4) adequate nutrition and fluid therapy. B, during remission: 1) exclusion of precipitating factors (education of patients and family doctors), 2) information about on-line drug lists, and 3) mutation screening for family members and education about precipitating factors in mutation-positive family members. C, management of patients with recurrent attacks: 1) evaluation of the lifestyle, 2) evaluation of hormonal therapy in women, 3) prophylactic heme therapy, and 4) liver transplantation in patients with severe recurrent attacks. D, follow-up of the AIP patients for long-term complications: chronic hypertension, chronic kidney insufficiency, chronic pain syndrome, and hepatocellular carcinoma. PMID- 26366105 TI - EX-PRESS Glaucoma Filtration Device: efficacy, safety, and predictability. AB - Trabeculectomy has been the traditional primary surgical therapy for open-angle glaucoma. While trabeculectomy is effective in lowering intraocular pressure, complications associated with the procedure have motivated the development of alternative techniques and devices, including the EX-PRESS Glaucoma Filtration Device. This review describes the efficacy, safety, complication rates, and potential advantages and disadvantages of the EX-PRESS Glaucoma Filtration Device. EX-PRESS implantation is technically simpler compared with that of trabeculectomy, with fewer surgical steps. Vision recovery has been more rapid after EX-PRESS implantation compared with trabeculectomy. Intraocular pressure variation is lower during the early postoperative period, indicating a more predictable procedure. While efficacy of the EX-PRESS implant has been comparable to trabeculectomy, postoperative complications appear less common after EX-PRESS implantation compared with trabeculectomy. The EX-PRESS Glaucoma Filtration Device appears to be safe and effective in the surgical management of open-angle glaucoma. PMID- 26366106 TI - Disaster risk profile and existing legal framework of Nepal: floods and landslides. AB - Nepal has a complicated geophysical structure that is prone to various kinds of disasters. Nepal ranks the most disaster-prone country in the world and has experienced several natural calamities, causing high property and life losses. Disasters are caused by natural processes, but may be increased by human activities. The overall objective of this paper is to analyze the disaster risk profile and existing legal framework of Nepal. The paper is based on secondary data sources. Major causative factors for floods and landslides are heavy and continuous rainfall, outburst floods, infrastructure failure, and deforestation. Historical data of natural disasters in Nepal show that water-induced disasters have killed hundreds of people and affected thousands every year. Likewise, properties worth millions of US dollars have been damaged. There is an increasing trend toward landslides and floods, which will likely continue to rise if proper intervention is not taken. A positive correlation between water-induced disasters and deaths has been observed. Nepal has a poor Index for Risk Management (INFORM). There are fluctuations in the recording of death data caused by flood and landslides. The Government of Nepal focuses more on the response phase than on the preparedness phase of disasters. The existing disaster management act seems to be weak and outdated. There is a gap in current legal procedure, so the country is in dire need of a comprehensive legal framework. The new proposed act seems to take a much broader approach to disaster management. With a long-term vision of managing disaster risk in the country, the Government of Nepal has begun the Nepal Risk Reduction Consortium (NRRC) in collaboration with development and humanitarian partners. In order to improve the vulnerability of Nepal, an early warning system, mainstreaming disasters with development, research activities, community participation and awareness, and a rainfall monitoring system must all be a focus. PMID- 26366107 TI - An automated sleep-state classification algorithm for quantifying sleep timing and sleep-dependent dynamics of electroencephalographic and cerebral metabolic parameters. AB - INTRODUCTION: Rodent sleep research uses electroencephalography (EEG) and electromyography (EMG) to determine the sleep state of an animal at any given time. EEG and EMG signals, typically sampled at >100 Hz, are segmented arbitrarily into epochs of equal duration (usually 2-10 seconds), and each epoch is scored as wake, slow-wave sleep (SWS), or rapid-eye-movement sleep (REMS), on the basis of visual inspection. Automated state scoring can minimize the burden associated with state and thereby facilitate the use of shorter epoch durations. METHODS: We developed a semiautomated state-scoring procedure that uses a combination of principal component analysis and naive Bayes classification, with the EEG and EMG as inputs. We validated this algorithm against human-scored sleep state scoring of data from C57BL/6J and BALB/CJ mice. We then applied a general homeostatic model to characterize the state-dependent dynamics of sleep slow-wave activity and cerebral glycolytic flux, measured as lactate concentration. RESULTS: More than 89% of epochs scored as wake or SWS by the human were scored as the same state by the machine, whether scoring in 2-second or 10-second epochs. The majority of epochs scored as REMS by the human were also scored as REMS by the machine. However, of epochs scored as REMS by the human, more than 10% were scored as SWS by the machine and 18 (10-second epochs) to 28% (2-second epochs) were scored as wake. These biases were not strain-specific, as strain differences in sleep-state timing relative to the light/dark cycle, EEG power spectral profiles, and the homeostatic dynamics of both slow waves and lactate were detected equally effectively with the automated method or the manual scoring method. Error associated with mathematical modeling of temporal dynamics of both EEG slow-wave activity and cerebral lactate either did not differ significantly when state scoring was done with automated versus visual scoring, or was reduced with automated state scoring relative to manual classification. CONCLUSIONS: Machine scoring is as effective as human scoring in detecting experimental effects in rodent sleep studies. Automated scoring is an efficient alternative to visual inspection in studies of strain differences in sleep and the temporal dynamics of sleep-related physiological parameters. PMID- 26366108 TI - Emerging and future therapies for hemophilia. AB - The evolution of care in hemophilia is a remarkable story. Over the last 60 years, advances in protein purification, protein chemistry, donor screening, viral inactivation, gene sequencing, gene cloning, and recombinant protein production have dramatically enhanced the treatment and lives of patients with hemophilia. Recent efforts have produced enhanced half-life (EHL) clotting factors to better support prophylaxis and decrease the frequency of infusions. Medical needs remain in the areas of alternate modes of administration to decrease the need for venous access, better treatment, and prophylaxis for patients who form antibodies to clotting factors, and ultimately a cure of the underlying genetic defect. In this brief review, the authors summarize data on EHL clotting factors, introduce agents whose mode of action is not clotting factor replacement, and list current gene therapy efforts. PMID- 26366109 TI - Breast fibroadenomas in adolescents: current perspectives. AB - Fibroadenomas are one of the most common benign tumors of the breast in the adolescent population. They account for 68% of all breast masses and 44%-94% of all biopsied breast lesions. Fibroadenomas can range from asymptomatic masses to painful and rapidly growing tumors that can cause significant esthetic distortions of the breast. Given the prevalence of fibroadenomas in the adolescent population and the psychosocial morbidity of finding a mass in the adolescent breast, it is imperative for physicians treating adolescent patients to be familiar and up to date with this disease process. The goal of this article is to provide a brief review of the classification, etiology, symptoms, initial work-up, and update on the management of breast fibroadenomas in the adolescent population. PMID- 26366110 TI - A universal intercalated undergraduate management program: attraction or deterrent? PMID- 26366111 TI - Acid detergent lignin, lodging resistance index, and expression of the caffeic acid O-methyltransferase gene in brown midrib-12 sudangrass. AB - Understanding the relationship between acid detergent lignin (ADL) and lodging resistance index (LRI) is essential for breeding new varieties of brown midrib (bmr) sudangrass (Sorghum sudanense (Piper) Stapf.). In this study, bmr-12 near isogenic lines and their wild-types obtained by back cross breeding were used to compare relevant forage yield and quality traits, and to analyze expression of the caffeic acid O-methyltransferase (COMT) gene using quantitative real time PCR. The research showed that the mean ADL content of bmr-12 mutants (20.94 g kg( 1)) was significantly (P < 0.05) lower than measured in N-12 lines (43.45 g kg( 1)), whereas the LRI of bmr-12 mutants (0.29) was significantly (P < 0.05) higher than in N-12 lines (0.22). There was no significant correlation between the two indexes in bmr-12 materials (r = -0.44, P > 0.05). Sequence comparison of the COMT gene revealed two point mutations present in bmr-12 but not in the wild type, the second mutation changed amino acid 129 of the protein from Gln (CAG) to a stop codon (UAG). The relative expression level of COMT gene was significantly reduced, which likely led to the decreased ADL content observed in the bmr-12 mutant. PMID- 26366112 TI - Genetic variation for maize root architecture in response to drought stress at the seedling stage. AB - Although the root system is indispensable for absorption of nutrients and water, it is poorly studied in maize owing to the difficulties of direct measurement of roots. Here, 103 maize lines were used to compare root architectures under well watered and water-stressed conditions. Significant genetic variation, with medium to high heritability and significant correlations, was observed for root traits. Total root length (TRL) and total root surface area (TSA) had high phenotypical diversity, and TRL was positively correlated with TSA, root volume, and root forks. The first two principal components explained 94.01% and 91.15% of total root variation in well-watered and water-stressed conditions, respectively. Thus, TRL and TSA, major contributors to root variation, can be used as favorable selection criteria at the seedling stage. We found that stiff stalk and non-stiff stalk groups (temperate backgrounds) showed relatively higher mean values for root morphological diversity than the TST group (tropical/subtropical background). Of the tested lines, 7, 42, 45, and 9 were classified as drought sensitive, moderately sensitive, moderately drought tolerant, and highly drought tolerant, respectively. Seven of the 9 extremely drought tolerant lines were from the TST group, suggesting that TST germplasms harbor valuable genetic resources for drought tolerance that could be used in breeding to improve abiotic stress tolerance in maize. PMID- 26366113 TI - Advanced backcross QTL analysis reveals complicated genetic control of rice grain shape in a japonica * indica cross. AB - Grain shape is an important trait for improving rice yield. A number of quantitative trait loci (QTLs) for this trait have been identified by using primary F2 mapping populations and recombinant inbred lines, in which QTLs with a small effect are harder to detect than they would be in advanced generations. In this study, we developed two advanced mapping populations (chromosome segment substitution lines [CSSLs] and BC4F2 lines consisting of more than 2000 individuals) in the genetic backgrounds of two improved cultivars: a japonica cultivar (Koshihikari) with short, round grains, and an indica cultivar (IR64) with long, slender grains. We compared the ability of these materials to reveal QTLs for grain shape with that of an F2 population. Only 8 QTLs for grain length or grain width were detected in the F2 population, versus 47 in the CSSL population and 65 in the BC4F2 population. These results strongly suggest that advanced mapping populations can reveal QTLs for agronomic traits under complicated genetic control, and that DNA markers linked with the QTLs are useful for choosing superior allelic combinations to enhance grain shape in the Koshihikari and IR64 genetic backgrounds. PMID- 26366114 TI - Puroindoline allelic diversity in Indian wheat germplasm and identification of new allelic variants. AB - Grain hardness is an important quality trait that influences product development in wheat. This trait is governed by variation in puroindoline proteins (PINA and PINB). Our study evaluated 551 Indian wheat germplasm lines for diversity in Pina and Pinb genes. Eighty-two lines were shortlisted for full length sequencing and grain hardness studies. Sequencing studies identified six unknown alleles: two for the Pina gene and four for the Pinb gene. Five of them were novel with non synonymous changes in the corresponding amino acid sequences. Identified mutations in the deduced mature proteins and their pre- and pro-peptides influenced the hardness characteristics of the grain. We classified these 82 varieties into different hardness categories with reference to international and Indian systems of classification. The majority of Indian wheat varieties were categorized as hard. This study revealed that unexplored Indian wheat germplasm can be a good source of genetic variability for both Pina and Pinb genes, helping in marker-assisted breeding and in obtaining wheat with different textural properties. PMID- 26366115 TI - Characterization and genetic mapping of eceriferum-ym (cer-ym), a cutin deficient barley mutant with impaired leaf water retention capacity. AB - The cuticle covers the aerial parts of land plants, where it serves many important functions, including water retention. Here, a recessive cuticle mutant, eceriferum-ym (cer-ym), of Hordeum vulgare L. (barley) showed abnormally glossy spikes, sheaths, and leaves. The cer-ym mutant plant detached from its root system was hypersensitive to desiccation treatment compared with wild type plants, and detached leaves of mutant lost 41.8% of their initial weight after 1 h of dehydration under laboratory conditions, while that of the wild type plants lost only 7.1%. Stomata function was not affected by the mutation, but the mutant leaves showed increased cuticular permeability to water, suggesting a defective leaf cuticle, which was confirmed by toluidine blue staining. The mutant leaves showed a substantial reduction in the amounts of the major cutin monomers and a slight increase in the main wax component, suggesting that the enhanced cuticle permeability was a consequence of cutin deficiency. cer-ym was mapped within a 0.8 cM interval between EST marker AK370363 and AK251484, a pericentromeric region on chromosome 4H. The results indicate that the desiccation sensitivity of cer-ym is caused by a defect in leaf cutin, and that cer-ym is located in a chromosome 4H pericentromeric region. PMID- 26366116 TI - Development of photoperiod- and thermo-sensitive male sterility rice expressing transgene Bacillus thuringiensis. AB - Stem borers and leaffolders are the main pests that cause severe damage in rice (Oryza sativa L.) production worldwide. We developed the first photoperiod- and thermo-sensitive male sterility (PTSMS) rice 208S with the cry1Ab/1Ac Bacillus thuringiensis (Bt) gene, through sexual crossing with Huahui 1 (elite line with the cry1Ab/1Ac gene). The novel 208S and its hybrids presented high and stable resistance to stem borers and leaffolders, and the content of Cry1Ab/1Ac protein in chlorophyllous tissues achieved the identical level as donor and showed little accumulation in non-chlorophyllous tissue. No dominant dosage effect in the Bt gene was observed in 208S and its derived hybrids. An analysis of fertility transition traits indicated that 208S was completely sterile under long day length/high temperature, but partially fertile under short day length/low temperature. With fine grain quality and favorable combining ability, 208S had no observed negative effects on fertility and agronomic traits from Bt (cry1Ab/1Ac). Additionally, 208S as a male sterile line showed no fertility decrease caused by Bt transgenic process, as it is the case in Huahui 1. Thus, 208S has great application value in two-line hybrid production for insect resistance, and can also be used as a bridge material in rice Bt transgenic breeding. PMID- 26366117 TI - Distorted genetic segregation of the transposon mPing at the long arm of chromosome 12 in rice. AB - A class II transposable element, mPing exists in the rice genome ubiquitously and can transpose even in ordinary cultivation conditions. A copy of mPing was identified at the long arm of chromosome 12. In reciprocal backcrossed F1s between a heterozygote and a homozygote without mPing, the male gametes with this mPing from heterozygotes were transmitted to the next generation at a lower frequency than those without mPing, resulting in distorted genetic segregation in self-fertilized progenies, as well as in F1s after backcrossing. Pollens with mPing tended to germinate on stigma less than those without mPing. These results, however, could not explain the lower transmission of male gametes with mPing. In addition, no excision of mPing was observed in a homozygote. Thus, it was suggested that male gametes with mPing were eliminated partly from pollination to fertilization by negative competition against male gametes without mPing. Less formation of microspores with mPing in meiosis could also be a cause for the distorted segregation, although this could not be examined. At least two ORFs, whose functions have not been identified, are located near this mPing. It is plausible that either of these ORFs or both are necessary for the normal functioning of male gametes. PMID- 26366118 TI - Rice tungro spherical virus resistance into photoperiod-insensitive japonica rice by marker-assisted selection. AB - Rice tungro disease (RTD) is one of the destructive and prevalent diseases in the tropical region. RTD is caused by Rice tungro spherical virus (RTSV) and Rice tungro bacilliform virus. Cultivation of japonica rice (Oryza sativa L. ssp japonica) in tropical Asia has often been restricted because most japonica cultivars are sensitive to short photoperiod, which is characteristic of tropical conditions. Japonica1, a rice variety bred for tropical conditions, is photoperiod-insensitive, has a high yield potential, but is susceptible to RTD and has poor grain quality. To transfer RTD resistance into Japonica1, we made two backcrosses (BC) and 8 three-way crosses (3-WC) among Japonica1 and RTSV resistant cultivars. Among 8,876 BC1F2 and 3-WCF2 plants, 342 were selected for photoperiod-insensitivity and good grain quality. Photoperiod-insensitive progenies were evaluated for RTSV resistance by a bioassay and marker-assisted selection (MAS), and 22 BC1F7 and 3-WCF7 lines were selected based on the results of an observational yield trial. The results demonstrated that conventional selection for photoperiod-insensitivity and MAS for RTSV resistance can greatly facilitate the development of japonica rice that is suitable for cultivation in tropical Asia. PMID- 26366119 TI - Inheritance of low pasting temperature in sweetpotato starch and the dosage effect of wild-type alleles. AB - Sweetpotato (Ipomoea batatas (L.) Lam.), which is an outcrossing hexaploid, is one of the most important starch-producing crops in the world. During the last decade, new sweetpotato cultivars, e.g. 'Quick Sweet', which have approximately 20 degrees C lower pasting temperature, slower retrogradation and higher digestibility of raw starch than ordinary cultivars, have been developed in Japan. Genetic analysis of these variants with low pasting temperature starch was conducted in this study. Using 8 variants and 15 normal clones, 26 families were generated. The results from analyzing these progenies suggested that this trait is a qualitative character controlled by one recessive allele (designated spt), which is inherited in a hexasomic manner. A dosage effect of the wild-type Spt allele was found for starch pasting temperature, although the effect was not linear. These results will aid breeders to develop sweetpotato cultivars with a range of starch pasting temperatures. PMID- 26366120 TI - PCR-based INDEL markers co-dominant between Oryza sativa, japonica cultivars and closely-related wild Oryza species. AB - Wild relatives genetically close to cultivars are precious genetic resources for plant breeding. Oryza rufipogon, O. barthii, O. glumaepatula, O. meridionalis and O. longistaminata are such wild species, and are also categorized as AA genome species based on their structural similarities. Chromosome segment substitution lines (CSSLs) are a powerful resource in breeding and genetics, and numerous rice CSSLs have been produced. This study aimed to develop DNA markers for evaluation of CSSLs directly by PCR and subsequent gel electrophoresis. We confirmed that up to 155 of 188 markers developed for detection of japonica-indica INDELs could also detect INDELs between rice cultivars and wild AA-species accessions. Percentages of applicable markers were higher in O. rufipogon accessions (61.7 to 85.6%), and lower in accessions of other four AA species (39.8 to 51.4%). These markers were distributed throughout the rice chromosomes, and will be useful for genotyping of CSSLs and other genetic resources derived from crosses between rice cultivars and closely related wild species. PMID- 26366121 TI - Are atopy and eosinophilic bronchial inflammation associated with relapsing forms of chronic rhinosinusitis with nasal polyps? AB - BACKGROUND: The aetiopathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) is still unknown. The role of atopy and the concept of united airways in such patients are still a matter of debate. In this pilot study we aimed at evaluating the degree of eosinophilic inflammation and the frequency of atopy in a cohort of CRSwNP patients candidate for Functional Endoscopic Sinus Surgery (FESS) and assessing the association between these factors and relapsing forms of CRSwNP. METHODS: 30 patients (18 men, 12 women) with CRSwNP eligible for FESS were evaluated before and after surgery. Preoperative investigation included: history of previous relapse after FESS, clinical and laboratory allergologic assessment, spirometry, methacholine challenge, blood eosinophilia and determination of the fraction of nitric oxide in exhaled air (FeNO). Nasal fibroendoscopy, spirometry and FeNO determination were also assessed prospectively at 3 and 27 months post-FESS. RESULTS: 18/30 subjects were atopic, 6/18 (33 %) were monosensitized, 16/30 (53 %) were asthmatics and 10/30 (33 %) had non steroidalantinflammatory drugs (NSAIDs) hypersensitivity. Twenty-one patients (70 %) were classified as relapsers, 15/18 (83 %) among atopics, 6/12 (50 %) among non atopics (p = 0.05). Among patients with NSAIDs hypersensitivity, 9/10 (90 %) were relapsers. The median IgE concentration was 161.5 UI/mL in relapsers and 79 UI/mL in non-relapsers (ns). The mean FeNO decreased after FESS (43.1-26.6 ppb) in 84 % of patients, but this effect disappeared over time (FeNO = 37.7 ppb at 27 months). Higher levels of FeNO pre-FESS were detected in atopics, and in particular in relapsing ones (median 51.1 ppb vs 22.1, ns). Higher levels of FeNO pre-FESS were detected in asthmatic patients, especially in those who relapsed (median: 67 vs 64.85 ppb in non-relapsed patients, ns). The Tiffeneau Index (FEV1/FVC) was significantly lower in asthmatic relapsers than in non relapsers asthmatics (94.7 +/- 11.1 versus 105 +/- 5.9-p = 0.04). Patients with asthma and atopy had a major risk of relapse (p = 0.05). CONCLUSION: In our pilot study, atopy, severe asthma, bronchial inflammation, NSAIDs hypersensitivity and high level of total IgE are possible useful prognostic factors for the proneness to relapse after FESS. The role of allergy in CRSwNP pathogenesis should consequently be given deeper consideration. Allergen specific immunotherapy, combined with anti-IgE therapy, may have an immunomodulatory effect preventing polyps relapse and need to be investigated. PMID- 26366122 TI - Is chest X-ray screening for lung cancer in smokers cost-effective? Evidence from a population-based study in Italy. AB - BACKGROUND: After implementation of the PREDICA annual chest X-ray (CXR) screening program in smokers in the general practice setting of Varese-Italy a significant reduction in lung cancer-specific mortality (18 %) was observed. The objective of this study covering July 1997 through December 2006 was to estimate the cost-effectiveness of this intervention. METHODS: We examined detailed information on lung cancer (LC) cases that occurred among smokers invited to be screened in the PREDICA study (Invitation-to-screening Group, n = 5815 subjects) to estimate costs and quality-adjusted life-years (QALYs) from LC diagnosis until death. The control group consisted of 156 screening-eligible smokers from the same area, uninvited and unscreened, who developed LC and were treated by usual care. We calculated the incremental net monetary benefit (INMB) by comparing LC management in screening participants (n = 1244 subjects) and in the Invitation-to screening group versus control group. RESULTS: The average number of QALYs since LC diagnosis was 1.7, 1.49 and 1.07, respectively, in screening participants, the invitation-to-screening group, and the control group. The average total cost (screening + management) per LC case was higher in screening participants (?17,516) and the Invitation-to-screening Group (?16,167) than in the control group (?15,503). Assuming a maximum willingness to pay of ?30,000/QALY, we found that the intervention was cost-effective with high probability: 79 % for screening participation (screening participants vs. control group) and 95 % for invitation-to-screening (invitation-to-screening group vs. control group). CONCLUSIONS: Based on the PREDICA study, annual CXR screening of high-risk smokers in a general practice setting has high probability of being cost effective with a maximum willingness to pay of ?30,000/QALY. PMID- 26366124 TI - Reinforcing Spirals Model: Conceptualizing the Relationship Between Media Content Exposure and the Development and Maintenance of Attitudes. AB - The Reinforcing Spirals Model (RSM, Citation Withheld) has two primary purposes. First, the RSM provides a general framework for conceptualizing media use as part of a dynamic, endogenous process combining selective exposure and media effects that may be drawn on by theorists concerned with a variety of social processes and effects. Second, the RSM utilizes a systems-theory perspective to describe how patterns of mediated and interpersonal communication contribute to the development and maintenance of social identities and ideology as well as more transient attitudes and related behaviors, and how those outcomes may influence subsequent media use. The RSM suggests contingencies that may lead to homeostasis or encourage certain individuals or groups to extreme polarization of such attitudes. In addition, the RSM proposes social cognitive mechanisms that may be responsible for attitude maintenance and reinforcement. This article discusses empirical progress in testing the model, addresses misconceptions that have arisen, and provides elaborated illustrations of the model. The article also identifies potentially fruitful directions for further conceptual development and empirical testing of the RSM. PMID- 26366123 TI - The Effect of Sleep Disturbances on Major Depressive Disorder. AB - Sleep disturbances not only commonly occur in major depressive disorder, but constitute one of the symptom criteria. Importantly, there is growing inference that sleep disturbances may be more than a symptomatic byproduct of depression; poor sleep may play a role in the development or clinical course of depression, or both. This article reviews the prevalence of the two major classes of sleep disorders, the insomnias and the sleep-disordered breathing disorders, as they pertain to depression. Beyond prevalence, the empirical evidence reviewed suggests that insomnia is a risk factor for depression and that obstructive sleep apnea (OSA) is highly associated with depression. Preliminary evidence indicates that OSA may also be a risk factor for this disorder. The implications of these findings for the treatment of sleep disturbances either prior to or in the context of depression are discussed. PMID- 26366125 TI - Older adult drivers living in residential care facilities. AB - Residential care facilities (RCF) provide assistance to older adults who cannot live independently, but it is unclear whether these residents have retired from driving. Here, we characterize older adults living in RCFs who still drive from a national cross-sectional survey of residents (2010 National Survey of Residential Care Facilities), representing ~733,000 adults living in RCFs such as assisted living facilities and personal care homes. Key resident characteristics were health, function, mobility and community activity indicators, which could be associated with increased driving risk. Of 8,087 residents, 4.5% (95%CI=3.9-5.1) were current drivers. Many drivers were older than 80 years (74%, 95%CI=67-79), in very good health (31%, 95%CI=25-38) or good health (35%, 95%CI=29-42), and had a median of two medical conditions. Most were independent with activities of daily living, though some needed assistance with walking and used gait devices. Given these results, RCF staff and healthcare providers need a heightened awareness of factors associated with driving risk to promote safety of older drivers and provide resources for likely transition to other transportation. PMID- 26366126 TI - Unheard Voices: African American Fathers Speak about their Parenting Practices. AB - Researchers have called for qualitative investigations into African American fathers' parenting practices that consider their social context and identify specific practices. Such investigations can inform the way we conceptualize African American fathers' parenting practices, which can in turn contribute to prevention interventions with at-risk youth. We conducted semi-structured, qualitative interviews about parenting with 30 self-identified, African American, biological fathers of pre-adolescent sons at-risk for developing aggressive behaviors, depressive symptoms, or both. Fathers provided descriptions of their parenting practices, which were at times influenced by their environmental context, fathers' residential status, and masculine ideologies. Our systematic analysis revealed four related themes that emerged from the data: managing emotions, encouragement, discipline, and monitoring. Of particular note, fathers in the current sample emphasized the importance of teaching their sons to manage difficult emotions, largely utilized language consistent with male ideologies (i.e., encouragement rather than love or nurturance), and engaged in high levels of monitoring and discipline in response to perceived environmental challenges and the developmental needs of their sons. The findings provide deeper insight into the parenting practices of African American fathers who are largely understudied, and often misunderstood. Further, these findings highlight considerations that may have important implications for father-focused prevention interventions that support African American fathers, youth, and families. PMID- 26366127 TI - Complex Behavior of Caffeine Crystallites on Muscovite Mica Surfaces. AB - Defined fabrication of organic thin films is highly desired in technological, as well as pharmaceutical, applications since morphology and crystal structure are directly linked to physical, electrical, and optical properties. Within this work, the directed growth of caffeine deposited by hot wall epitaxy (HWE) on muscovite mica is studied. Optical and atomic force microscopy measurements reveal the presence of caffeine needles exhibiting a preferable alignment in the azimuthal directions with respect to the orientation of the defined mica surface. Specular X-ray diffraction and X-ray diffraction pole figure measurements give evidence that the beta-polymorphic form of caffeine forms on the mica surface. All results consent that caffeine molecules have an edge-on conformation i.e. minimizing their interaction area with the surface. Furthermore, the azimuthal alignment of the long caffeine needle axis takes place along the [110], [100], and [110] real space directions of mica; needles are observed every 60 degrees azimuthally. While mica has a complex surface structure with mirror planes and lowered oxygen rows, the slightly disturbed 3-fold symmetry dictates the crystal alignment. This is different to previous findings for solution cast caffeine growth on mica. For HWE the needles align solely along the mica main directions whereby solution cast needles show an additional needle splitting due to a different alignment of caffeine with respect to the surface. PMID- 26366128 TI - Surface-Induced Polymorphism as a Tool for Enhanced Dissolution: The Example of Phenytoin. AB - Polymorphism and morphology can represent key factors tremendously limiting the bioavailability of active pharmaceutical ingredients (API), in particular, due to solubility issues. Within this work, the generation of a yet unknown surface induced polymorph (SIP) of the model drug, 5,5-diphenylimidazolidin-2,4-dion (phenytoin), is demonstrated in thin films through altering the crystallization kinetics and the solvent type. Atomic force microscopy points toward the presence of large single-crystalline domains of the SIP, which is in contrast to samples comprising solely the bulk phase, where extended dendritic phenytoin networks are observed. Grazing incidence X-ray diffraction reveals unit cell dimensions of the SIP significantly different from those of the known bulk crystal structure of phenytoin. Moreover, the aqueous dissolution performance of the new polymorph is benchmarked against a pure bulk phase reference sample. Our results demonstrate that the SIP exhibits markedly advantageous drug release performance in terms of dissolution time. These findings suggest that thin-film growth of pharmaceutical systems in general should be explored, where poor aqueous dissolution represents a key limiting factor in pharmaceutical applications, and illustrate the experimental pathway for determining the physical properties of a pharmaceutically relevant SIP. PMID- 26366129 TI - Barriers to Implementation of Rapid and Point-of-Care Tests for Human Immunodeficiency Virus Infection: Findings From a Systematic Review (1996-2014). AB - : Implementation of human immunodeficiency virus rapid and point-of-care tests (RDT/POCT) is understood to be impeded by many different factors that operate at 4 main levels-test devices, patients, providers, and health systems-yet a knowledge gap exists of how they act and interact to impede implementation. To fill this gap, and with a view to improving the quality of implementation, we conducted a systematic review. METHODS: Five databases were searched, 16,672 citations were retrieved, and data were abstracted on 132 studies by 2 reviewers. FINDINGS: Across 3 levels (ie, patients, providers, and health systems), a majority (59%, 112/190) of the 190 barriers were related to the integration of RDT/POCT, followed by test-device-related concern (ie, accuracy) at 41% (78/190). At the patient level, a lack of awareness about tests (15/54, 28%) and time taken to test (12/54, 22%) dominated. At the provider and health system levels, integration of RDT/POCT in clinical workflows (7/24, 29%) and within hospitals (21/34, 62%) prevailed. Accuracy (57/78, 73%) was dominant only at the device level. INTERPRETATION: Integration barriers dominated the findings followed by test accuracy. Although accuracy has improved during the years, an ideal implementation could be achieved by improving the integration of RDT/POCT within clinics, hospitals, and health systems, with clear protocols, training on quality assurance and control, clear communication, and linkage plans to improve health outcomes of patients. This finding is pertinent for a future envisioned implementation and global scale-up of RDT/POCT-based initiatives. PMID- 26366130 TI - Depression and Service Use Among Caregivers Dually Involved in the Child Welfare and Mental Health Systems. AB - INTRODUCTION: The purpose of this study was to investigate the prevalence of depression, use of mental health services, and correlates of service use among caregivers who are dually involved in the child welfare and child mental health systems. METHODS: This study analyzed baseline data from 129 caregivers who reported child welfare system involvement and were participating in a Multiple Family Group service delivery model to reduce childhood disruptive behavior disorders. RESULTS: Seventy-eight (60.5%) of caregivers met or exceed the clinical-cut off for depression; of them 50 (64.1%) reported utilizing mental health services for their emotional health. Race, employment status, and CES-D score were significantly associated with lifetime mental heath services use. DISCUSSION: Depression rates exceeded those found among caregiver involved in either the child welfare or child mental health systems. Rates of service use were higher than found in existing research. As expected, racial differences and depression were associated with service use; contrary to expectations, full time employment was not associated with service use. Discrepancies between this study and existing research are discussed, as are practice, policy, and research implications. PMID- 26366132 TI - Possible Selves: Implications for Psychotherapy. AB - The paper is devoted to the therapeutic applications of theories and research concerning self-regulation issues. The key concept here is possible selves, defined as an element of self-knowledge that refers to what a person perceives as potentially possible. The main idea of using knowledge about possible selves in psychotherapy is based on their functions as standards in self-regulatory processes. The problem of the changeability of possible selves and self-standards is analyzed in the context of their role in behavior change. The paper also presents the assumptions of Self-System Therapy - a newly developed cognitive therapy for depression, drawing directly on self-regulation theory and research. PMID- 26366131 TI - Computing Protein-Protein Association Affinity with Hybrid Steered Molecular Dynamics. AB - Computing protein-protein association affinities is one of the fundamental challenges in computational biophysics/biochemistry. The overwhelming amount of statistics in the phase space of very high dimensions cannot be sufficiently sampled even with today's high-performance computing power. In this article, we extend a potential of mean force (PMF)-based approach, the hybrid steered molecular dynamics (hSMD) approach we developed for ligand-protein binding, to protein-protein association problems. For a protein complex consisting of two protomers, P1 and P2, we choose m (>=3) segments of P1 whose m centers of mass are to be steered in a chosen direction and n (>=3) segments of P2 whose n centers of mass are to be steered in the opposite direction. The coordinates of these m + n centers constitute a phase space of 3(m + n) dimensions (3(m + n)D). All other degrees of freedom of the proteins, ligands, solvents, and solutes are freely subject to the stochastic dynamics of the all-atom model system. Conducting SMD along a line in this phase space, we obtain the 3(m + n)D PMF difference between two chosen states: one single state in the associated state ensemble and one single state in the dissociated state ensemble. This PMF difference is the first of four contributors to the protein-protein association energy. The second contributor is the 3(m + n - 1)D partial partition in the associated state accounting for the rotations and fluctuations of the (m + n - 1) centers while fixing one of the m + n centers of the P1-P2 complex. The two other contributors are the 3(m - 1)D partial partition of P1 and the 3(n - 1)D partial partition of P2 accounting for the rotations and fluctuations of their m - 1 or n - 1 centers while fixing one of the m/n centers of P1/P2 in the dissociated state. Each of these three partial partitions can be factored exactly into a 6D partial partition in multiplication with a remaining factor accounting for the small fluctuations while fixing three of the centers of P1, P2, or the P1-P2 complex, respectively. These small fluctuations can be well-approximated as Gaussian, and every 6D partition can be reduced in an exact manner to three problems of 1D sampling, counting the rotations and fluctuations around one of the centers as being fixed. We implement this hSMD approach to the Ras-RalGDS complex, choosing three centers on RalGDS and three on Ras (m = n = 3). At a computing cost of about 71.6 wall-clock hours using 400 computing cores in parallel, we obtained the association energy, -9.2 +/- 1.9 kcal/mol on the basis of CHARMM 36 parameters, which well agrees with the experimental data, -8.4 +/- 0.2 kcal/mol. PMID- 26366133 TI - Impact of collection conditions on the metabolite content of human urine samples as analyzed by liquid chromatography coupled to mass spectrometry and nuclear magnetic resonance spectroscopy. AB - There is a lack of comprehensive studies documenting the impact of sample collection conditions on metabolic composition of human urine. To address this issue, two experiments were performed at a 3-month interval, in which midstream urine samples from healthy individuals were collected, pooled, divided into several aliquots and kept under specific conditions (room temperature, 4 degrees C, with or without preservative) up to 72 h before storage at -80 degrees C. Samples were analyzed by high-performance liquid chromatography coupled to high resolution mass spectrometry and bacterial contamination was monitored by turbidimetry. Multivariate analyses showed that urinary metabolic fingerprints were affected by the presence of preservatives and also by storage at room temperature from 24 to 72 h, whereas no change was observed for urine samples stored at 4 degrees C over a 72-h period. Investigations were then focused on 280 metabolites previously identified in urine: 19 of them were impacted by the kind of sample collection protocol in both experiments, including 12 metabolites affected by bacterial contamination and 7 exhibiting poor chemical stability. Finally, our results emphasize that the use of preservative prevents bacterial overgrowth, but does not avoid metabolite instability in solution, whereas storage at 4 degrees C inhibits bacterial overgrowth at least over a 72-h period and slows the chemical degradation process. Consequently, and for further LC/MS analyses, human urine samples should be kept at 4 degrees C if their collection is performed over 24 h. PMID- 26366135 TI - Development of tools for quantitative intracellular metabolomics of Aspergillus niger chemostat cultures. AB - In view of the high citric acid production capacity of Aspergillus niger, it should be well suited as a cell factory for the production of other relevant acids as succinic, fumaric, itaconic and malic. Quantitative metabolomics is an important omics tool in a synthetic biology approach to develop A. niger for the production of these acids. Such studies require well defined and tightly controlled cultivation conditions and proper rapid sampling, sample processing and analysis methods. In this study we present the development of a chemostat for homogeneous steady state cultivation of A. niger, equipped with a new dedicated rapid sampling device. A quenching method for quantitative metabolomics in A. niger based on cold methanol was evaluated using balances and optimized with the aim of avoiding metabolite leakage during sample processing. The optimization was based on measurements of the intermediates of the glycolysis, TCA and PPP pathways and amino acids, using a balance approach. Leakage was found to be absent at -20 degrees C for a 40 % (v/v) methanol concentration in water. Under these conditions the average metabolite recovery was close to 100 %. When comparing A. niger and Penicillium chrysogenum metabolomes, under the same cultivation conditions, similar metabolite fingerprints were found in both fungi, except for the intracellular citrate level which is higher for A. niger. PMID- 26366134 TI - Comprehensive metabolome analyses reveal N-acetylcysteine-responsive accumulation of kynurenine in systemic lupus erythematosus: implications for activation of the mechanistic target of rapamycin. AB - Systemic lupus erythematosus (SLE) patients exhibit depletion of the intracellular antioxidant glutathione and downstream activation of the metabolic sensor, mechanistic target of rapamycin (mTOR). Since reversal of glutathione depletion by the amino acid precursor, N-acetylcysteine (NAC), is therapeutic in SLE, its mechanism of impact on the metabolome was examined within the context of a double-blind placebo-controlled trial. Quantitative metabolome profiling of peripheral blood lymphocytes (PBL) was performed in 36 SLE patients and 42 healthy controls matched for age, gender, and ethnicity of patients using mass spectrometry that covers all major metabolic pathways. mTOR activity was assessed by western blot and flow cytometry. Metabolome changes in lupus PBL affected 27 of 80 KEGG pathways at FDR p < 0.05 with most prominent impact on the pentose phosphate pathway (PPP). While cysteine was depleted, cystine, kynurenine, cytosine, and dCTP were the most increased metabolites. Area under the receiver operating characteristic curve (AUC) logistic regression approach identified kynurenine (AUC = 0.859), dCTP (AUC = 0.762), and methionine sulfoxide (AUC = 0.708), as top predictors of SLE. Kynurenine was the top predictor of NAC effect in SLE (AUC = 0.851). NAC treatment significantly reduced kynurenine levels relative to placebo in vivo (raw p = 2.8 * 10-7, FDR corrected p = 6.6 * 10-5). Kynurenine stimulated mTOR activity in healthy control PBL in vitro. Metabolome changes in lupus PBL reveal a dominant impact on the PPP that reflect greater demand for nucleotides and oxidative stress. The PPP-connected and NAC-responsive accumulation of kynurenine and its stimulation of mTOR are identified as novel metabolic checkpoints in lupus pathogenesis. PMID- 26366136 TI - Scaling in ANOVA-simultaneous component analysis. AB - In omics research often high-dimensional data is collected according to an experimental design. Typically, the manipulations involved yield differential effects on subsets of variables. An effective approach to identify those effects is ANOVA-simultaneous component analysis (ASCA), which combines analysis of variance with principal component analysis. So far, pre-treatment in ASCA received hardly any attention, whereas its effects can be huge. In this paper, we describe various strategies for scaling, and identify a rational approach. We present the approaches in matrix algebra terms and illustrate them with an insightful simulated example. We show that scaling directly influences which data aspects are stressed in the analysis, and hence become apparent in the solution. Therefore, the cornerstone for proper scaling is to use a scaling factor that is free from the effect of interest. This implies that proper scaling depends on the effect(s) of interest, and that different types of scaling may be proper for the different effect matrices. We illustrate that different scaling approaches can greatly affect the ASCA interpretation with a real-life example from nutritional research. The principle that scaling factors should be free from the effect of interest generalizes to other statistical methods that involve scaling, as classification methods. PMID- 26366137 TI - Identification of putative biomarkers for prediabetes by metabolome analysis of rat models of type 2 diabetes. AB - Biomarkers for the development of type 2 diabetes (T2D) are useful for prediction and intervention of the disease at earlier stages. In this study, we performed a longitudinal study of changes in metabolites using an animal model of T2D, the spontaneously diabetic Torii (SDT) rat. Fasting plasma samples of SDT and control Sprague-Dawley (SD) rats were collected from 6 to 24 weeks of age, and subjected to gas chromatography-mass spectrometry-based metabolome analysis. Fifty-nine hydrophilic metabolites were detected in plasma samples, including amino acids, carbohydrates, sugars and organic acids. At 12 weeks of age, just before the onset of diabetes in SDT rats, the amounts of nine of these metabolites (asparagine, glutamine, glycerol, kynurenine, mannose, n-alpha-acetyllysine, taurine, threonine, and tryptophan) in SDT rats were significantly different from those in SD rats. In particular, metabolites in the tryptophan metabolism pathway (tryptophan and kynurenine) were decreased in SDT rats at 12 weeks of age and later. The lower tryptophan and kynurenine levels in the prediabetic state and later were further confirmed by a replication study on SDT rats and by a longitudinal study on another animal model of T2D, the Otsuka Long-Evans Tokushima Fatty rat. Our data indicate that tryptophan and its metabolites are potential biomarkers for prediabetes and that tryptophan metabolism may be a potential target of intervention for treatment of the disease. PMID- 26366138 TI - Application of NMR-based metabolomics for environmental assessment in the Great Lakes using zebra mussel (Dreissena polymorpha). AB - Zebra mussel, Dreissena polymorpha, in the Great Lakes is being monitored as a bio-indicator organism for environmental health effects by the National Oceanic and Atmospheric Administration's Mussel Watch program. In order to monitor the environmental effects of industrial pollution on the ecosystem, invasive zebra mussels were collected from four stations-three inner harbor sites (LMMB4, LMMB1, and LMMB) in Milwaukee Estuary, and one reference site (LMMB5) in Lake Michigan, Wisconsin. Nuclear magnetic resonance (NMR)-based metabolomics was used to evaluate the metabolic profiles of the mussels from these four sites. The objective was to observe whether there were differences in metabolite profiles between impacted sites and the reference site; and if there were metabolic profile differences among the impacted sites. Principal component analyses indicated there was no significant difference between two impacted sites: north Milwaukee harbor (LMMB and LMMB4) and the LMMB5 reference site. However, significant metabolic differences were observed between the impacted site on the south Milwaukee harbor (LMMB1) and the LMMB5 reference site, a finding that correlates with preliminary sediment toxicity results. A total of 26 altered metabolites (including two unidentified peaks) were successfully identified in a comparison of zebra mussels from the LMMB1 site and LMMB5 reference site. The application of both uni- and multivariate analysis not only confirmed the variability of altered metabolites but also ensured that these metabolites were identified via unbiased analysis. This study has demonstrated the feasibility of the NMR-based metabolomics approach to assess whole-body metabolomics of zebra mussels to study the physiological impact of toxicant exposure at field sites. PMID- 26366139 TI - Forecasting individual breast cancer risk using plasma metabolomics and biocontours. AB - Breast cancer is a major cause of death for women. To improve treatment, current oncology research focuses on discovering and validating new biomarkers for early detection of cancer; so far with limited success. Metabolic profiling of plasma samples and auxiliary lifestyle information was combined by chemometric data fusion. It was possible to create a biocontour, which we define as a complex pattern of relevant biological and phenotypic information. While single markers or known risk factors have close to no predictive value, the developed biocontour provides a forecast which, several years before diagnosis, is on par with how well most current biomarkers can diagnose current cancer. Hence, while e.g. mammography can diagnose current cancer with a sensitivity and specificity of around 75 %, the currently developed biocontour can predict that there is an increased risk that breast cancer will develop in a subject 2-5 years after the sample is taken with sensitivity and specificity well above 80 %. The model was built on data obtained in 1993-1996 and tested on persons sampled a year later in 1997. Metabolic forecasting of cancer by biocontours opens new possibilities for early prediction of individual cancer risk and thus for efficient screening. This may provide new avenues for research into disease mechanisms. PMID- 26366140 TI - Serially coupling hydrophobic interaction and reversed-phase chromatography with simultaneous gradients provides greater coverage of the metabolome. AB - The serial coupling of a reversed-phase liquid chromatography (RPLC) column to a hydrophilic interaction liquid chromatography (HILIC) column has been developed in recent years for the detection of polar and nonpolar metabolites. TCA intermediates, bile acid standards and numerous polar and non-polar metabolites extracted from beer were analysed using a combined RPLC/HILIC method. Non-polar metabolites were retained by the RPLC column. Polar metabolites not retained by the RPLC column were retained and separated by the HILIC column. The results from this study validate this simple yet powerful metabolomics approach. PMID- 26366141 TI - Seeing the Forest in Lieu of the Trees: Continuum Simulations of Cell Membranes at Large Length Scales. AB - Biological membranes exhibit long-range spatial structure in both chemical composition and geometric shape, which gives rise to remarkable physical phenomena and important biological functions. Continuum models that describe these effects play an important role in our understanding of membrane biophysics at large length scales. We review the mathematical framework used to describe both composition and shape degrees of freedom, and present best practices to implement such models in a computer simulation. We discuss in detail two applications of continuum models of cell membranes: the formation of microemulsion and modulated phases, and the effect of membrane-mediated interactions on the assembly of membrane proteins. PMID- 26366142 TI - Trait mindfulness and early maladaptive schemas in women seeking residential substance use treatment: A preliminary investigation. AB - Mindfulness has received an abundance of research attention in recent years, largely due to mindfulness-based interventions demonstrating positive mental and physical health outcomes. However, less research has examined individual's trait levels of mindfulness and how it is related to mental health, particularly among individuals seeking substance use treatment. Therefore, in the current study, we examined the relation between trait mindfulness and early maladaptive schemas (EMS), which are dysfunctional cognitive and behavioural patterns that theoretically underlie the development of mental health problems, among women seeking residential substance use treatment. Pre-existing, adult female, patient records from a residential substance abuse treatment facility were reviewed (N = 67). Results demonstrated that higher trait mindfulness was negatively associated with 12 of the 18 EMS. Moreover, patients who endorsed multiple EMS reported lower trait mindfulness than patients who endorsed zero (or one) EMS. These findings are the first to examine the relation between trait mindfulness and EMS among women seeking substance use treatment. Findings suggest that EMS and trait mindfulness are robustly related and future research should examine whether mindfulness-based interventions reduce EMS. PMID- 26366143 TI - Automated microfluidic processing platform for multiplexed magnetic bead immunoassays. AB - A microfluidic platform is presented which fully automates all incubation steps of a three-stage, multiplexed magnetic bead immunoassay, such as the Luminex(r) xMAP technology. Magnetic actuation is used to transfer the microbeads between co infused adjacent laminar flow streams to transport the beads into and out of incubation and wash solutions, with extended incubation channels to allow sufficient bead incubation times (1-30 min, commonly 5 min per stage) to enable high-sensitivity. The serial incubation steps of the immunoassay are completed in succession within the device with no operator interaction, and the continuous flow operation with magnetic bead transfer defines the incubation sequencing requiring no external fluidic controls beyond syringe pump infusion. The binding kinetics of the assay is empirically characterized to determine the required incubation times for specific assay sensitivities in the range 1 pg/ml to 100 ng/ml. By using a Luminex(r) xMAP duplex assay, concurrent detection of IL-6 and TNF-alpha was demonstrated on-chip with a detection range 10 pg/ml to 1 ng/ml. This technology enables rapid automation of magnetic microbead assays, and has the potential to perform continuous concentration monitoring. PMID- 26366144 TI - Features of home and neighbourhood and the liveability of older South Africans. AB - While older people live in developing countries, little is known about the relative importance of features of their communities in influencing their liveability. We examine components of home and neighbourhood among older South Africans. Linear regression analyses revealed that features of home (basic amenities, household composition, financial status and safety) and neighbourhood (ability to shop for groceries, participate in organizations and feel safe from crime) are significantly associated with life satisfaction. Approaches to liveability that are person-centred and also set within contexts beyond home and neighbourhood are needed to address boundaries between home and neighbourhood; incorporate personal resources into liveability models and import broader environmental contexts such as health and social policy. PMID- 26366145 TI - A Novel Bioinspired Switchable Adhesive with Three Distinct Adhesive States. AB - A novel switchable adhesive, inspired by the gecko's fibrillar dry attachment system, is introduced. It consists of a patterned surface with an array of mushroom-shaped pillars having two distinct heights. The different pillar heights allow control of the pull-off force in two steps by application of a low and a high preload. For low preload, only the long pillars form contact, resulting in a low pull-off force. At higher preload, all pillars form contact, resulting in high pull-off force. Even further loading leads to buckling induced detachment of the pillars which corresponds to extremely low pull-off force. To achieve the respective samples a new fabrication method called double inking is developed, to achieve multiple-height pillar structures. The adhesion performance of the two step switchable adhesive is analysed at varying preload and for different pillar aspect ratios and height relations. Finally, the deformation behavior of the samples is investigated by in situ monitoring. PMID- 26366147 TI - Autoimmunogenicity during anti-TNF therapy in patients with psoriasis and psoriatic arthritis. AB - INTRODUCTION: The tumor necrosis factor (TNF-alpha) was initially described as lymphotoxin or cachectin. The discovery of therapies blocking the action of TNF alpha, in 1988, started a new era in the therapy. One of often reported adverse effects related to the use of TNF-alpha antagonists is induction of the formation of autologous antibodies and antibodies neutralizing anti-TNF drugs. The development of anti-TNF-induced lupus or classical drug-induced lupus is more rarely reported. AIM: To evaluate the presence and the level of anti-nuclear antibodies in patients with psoriasis and psoriatic arthritis and the influence of anti-TNF therapy used on the concentration of antinuclear antibody (ANA). MATERIAL AND METHODS: A total of 28 subjects were included in the study. 71.4% of subjects were diagnosed with psoriatic arthritis and 28.6% with plaque psoriasis. RESULTS: Among the patients with plaque psoriasis, the antinuclear antibodies were found in 25% of subjects and in 80% of patients with psoriatic arthritis. After the treatment an increase in the titer or appearance of antibodies was found in 66.7% in the infliximab group, 18.2% in the etanercept group and 54.7% in the adalimumab group. No subjects developed symptoms of drug-induced systemic lupus. CONCLUSIONS: Our findings have shown that all anti-TNF therapies induced ANA in psoriatic arthritis and psoriatic patients. Considering a mild course of lupus induced by anti-TNF treatment and, usually intrinsic, resolution of symptoms, the biological therapy still appears as a safe treatment for patients. PMID- 26366146 TI - Atopic dermatitis: current treatment guidelines. Statement of the experts of the Dermatological Section, Polish Society of Allergology, and the Allergology Section, Polish Society of Dermatology. AB - Atopic dermatitis (AD) is a condition frequently encountered in medical practices across the country. More than 60% of children with AD are at risk to develop allergic rhinitis or asthma (the atopic march). Patients with AD have a unique predisposition to colonization or infection by Staphylococcus aureus. Treatments for AD need to rapidly control symptoms of the disease, improve quality of life and prevent exacerbations. Given the chronic and relapsing nature of the disease, therapies need to encourage good compliance and be well tolerated. PMID- 26366148 TI - Hypersensitivity to major panallergens in a population of 120 patients. AB - INTRODUCTION: Lipid transfer proteins (LTP), profilin and PR-10 are the most important panallergens in central and southern Italy. Lipid transfer proteins are stable molecules, predominantly present in the fruit peel, which can induce systemic symptoms after ingestion of vegetables. Profilin and PR-10 are randomly distributed in the pulp and peel. Both are labile proteins and usually determine reactions restricted to the oral cavity. Panallergens-specific IgE may cross react with homologues from different plant sources, due to their conserved structure. AIM: To assess the pattern of sensitization to panallergens and the correlation with the clinical history and the allergological evaluation of food and aeroallergens. MATERIAL AND METHODS: One hundred and twenty patients with adverse reactions after vegetables ingestion underwent skin prick tests (SPT) with commercial extracts of plant-derived foods and inhalant allergens and commercial extracts of LTP, profilin and PR-10. RESULTS: Many patients presented positive SPT with different plant-food allergens. We found that 76 patients were sensitized to LTP, 14 to profilin and 5 to PR-10. In the LTP-sensitized group, 64 (84%) patients suffered from systemic symptoms while the patients sensitized only to profilin referred the oral allergy syndrome. CONCLUSIONS: This study shows a high rate of sensitization to LTP in our population according to the literature about food allergy in our geographical area and confirms the literature data about the symptoms referred by patients with sensitization to panallergens. Panallergens should be considered as clinically relevant food allergens. PMID- 26366149 TI - IgE-mediated 15-hydroxyeicosatetraenoic acid (15-HETE) generation by peripheral blood leukocytes: its association with basophil activation. AB - INTRODUCTION: Allergen-induced basophil activation has been associated with the release of several mediators and with an increased expression of CD203c molecules on basophils. AIM: To assess the influence of specific allergens on the generation of 15-hydroxyeicosatetraenoic (15-HETE) from peripheral blood leukocytes in relation to basophil activation, on the basis of CD203c molecule expression and histamine release. MATERIAL AND METHODS: The study included 15 patients with clinical symptoms of birch pollen allergy confirmed by a positive skin prick test with the birch allergen, and 6 healthy controls. Leukocytes isolated from peripheral blood were incubated with 3 concentrations of the birch pollen allergen (Bet v 1), anti-IgE or with ionophore A23187. RESULTS: In vitro challenge of leukocytes from allergic patients with 1 ng/ml of allergen induced a significant increase in 15-HETE generation. An increase above 30% was observed in almost half the allergic patients, with mean values ranging from 40% to 46%, but not in healthy controls. Anti-IgE antibodies increased 15-HETE generation in 5 patients (termed IgE+), and the allergen induced a significant increase in 15 HETE in all patients who reacted to anti-IgE. The mean CD203c expression on basophils of the allergic patients increased after allergen challenge, but a significant increase (> 30%) was observed only in patients who demonstrated an increased expression after anti-IgE exposure. A significant correlation was seen between 15-HETE generation and histamine release induced by the highest concentration of the allergen (r = 0.95; p < 0.01). CONCLUSIONS: Allergen induced, IgE-mediated activation of basophils is associated with a significant increase in 15-HETE generation. PMID- 26366150 TI - A cross-sectional study of prevalence and risk factors for childhood asthma in Ahvaz city, Iran. AB - INTRODUCTION: Childhood asthma is the main public health problem in world, and dramatically has increased in developed as well as developing countries. AIM: To assess prevalence and risk factors for asthma based on ISAAC questionnaire. MATERIAL AND METHODS: It was a cross-sectional school population-based study which was carried out on 1803 school children aged 6-7 and 13-14 in Ahvaz city, Khuzestan, south west of Iran, in 2011. The International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire was used as a tool to identify prevalence of asthma. Chi-square (chi(2)) test was then used to identify possible potential risk factors associated with asthma. Logistic regression analysis was then applied to determine the various potential risk factors associated with asthma. Data were entered and analyzed using SPSS (version 17) statistical analysis software. The significant level in this study was considered 0.05. RESULTS: The overall prevalence of asthma among school children was 4.9%, but in males it was 5.5% and in females - 4.3%. Also findings have demonstrated that prevalence of asthma was higher among 13-14 years age group (6.1%) as compared to children aged 6-7 (3.7%). The prevalence of wheeze in the last 12 months, wheeze after exercise and playing was 18.1%, 13.9%, and 8.4% respectively. Prevalence of dry cough at night was reported in 17.6%. Prevalence of asthma was highest in winter (2.6%). CONCLUSIONS: Prevalence of asthma in children was higher in males than females and prevalence of allergic symptoms will be increased with high air pollution. Family history of asthma was a strong risk factor for childhood asthma. PMID- 26366151 TI - Prevalence of IgE-mediated allergy and evaluation of Th1/Th2 cytokine profiles in patients with severe bronchial asthma. AB - INTRODUCTION: The pathogenesis of asthma remains unclear, especially in cases of the severe disease. AIM: To explore IgE-mediated inhalant sensitization in severe asthma compared with a group of patients with chronic mild disease and evaluate the Th1/Th2 cytokine profiles in asthma by different disease severities. MATERIAL AND METHODS: One hundred and fifty-four patients (age range: 28-69) with severe chronic asthma (study group) and 141 patients with chronic mild disease (control group) diagnosed according to GINA criteria were included in the study. Seventy eight severe asthmatics and 43 subjects with mild disease were randomly selected for serum Th1/Th2 cytokine level estimation. The groups were matched in terms of age and atopy features (skin prick tests, specific and total serum IgE). RESULTS: Positive skin tests to at least one allergen were observed with comparable frequencies. Sensitization to Dermatophagoides pteronyssinus was the most prevalent positive result in both groups. An earlier onset of asthma together with a greater number of exacerbations was noted in severe asthmatics compared to patients with mild disease. Serum levels of interleukin 4 and 2 (IL-4 and IL-2) were detectable only in severe asthmatics irrespective of atopy features. The levels of interferon gamma and tumour necrosis factor alpha were undetectable in both groups. IL-10 and IL-5 were detected in the serum of only 7 and 12 severe asthmatics, respectively. CONCLUSIONS: The serum level of IL-2 and IL-4 could be perceived as a marker of severe asthma. Neither IL-2 nor IL-4 levels in the serum could differentiate allergic and non-allergic asthma. PMID- 26366152 TI - Insulin resistance in severe acne vulgaris. AB - INTRODUCTION: Acne vulgaris is a pilosebaceous gland disease that usually affects people from puberty to young adulthood. It is seen especially on the face, neck, trunk and arms. Its severity differs from patient to patient and its pathogenesis is multifactorial. The main pathogenic factors of acne are high sebaceous gland secretion, follicular hyperproliferation, high androgen effects, propionibacterium acnes colonization and inflammation. Diet is always thought a probable reason for acne and many studies are done about acne and diet. AIM: To determine the effect of insulin resistance in severe acne vulgaris. MATERIAL AND METHODS: Two hundred and forty-three acne vulgaris patients and 156 healthy controls were enrolled into the study. The blood levels of insulin and glucose were measured. Homeostasis Model Assessment (HOMA) Index was calculated. The values were compared with the control group. RESULTS: All of the patients were in the severe acne group according to their scores on the global acne scoring scale. While fasting blood glucose levels were not different between the groups (p > 0.05, 82.91 +/-9.76 vs. 80.26 +/-8.33), the fasting insulin levels were significantly higher in the patient group than in the control group (p < 0.001, 14.01 +/-11.94 vs. 9.12 +/-3.53). Additionally, there was a highly significant difference between the patient and control groups in terms of HOMA values (p < 0.001, 2.87 +/-2.56 vs. 1.63 +/-0.65). CONCLUSIONS: These results suggest that insulin resistance may have a role in the pathogenesis of acne. PMID- 26366153 TI - Serological test results of sexually transmitted diseases in patients with condyloma acuminata. AB - INTRODUCTION: Human papillomavirus (HPV) is one of the most common causes of sexually transmitted diseases (STD). The incidence of condyloma acuminata (CA) has increased in recent years. AIM: To determine demographical features and serological test results of STD in patients with CA. MATERIAL AND METHODS: A cross-sectional survey was conducted on 94 patients presenting to a dermatology clinic in Ankara, Middle Anatolia, Turkey. Dermatological examinations were made and the patients completed a questionnaire which consisted of questions about their marital status, partners and condom use. In all cases, VDRL/RPR, anti-HIV, HBsAg, anti-HCV and in 57 cases - HSV type 1-2 IgM and IgG were studied. If the value of VDRL or RPR was positive, TPHA was conducted. RESULTS: In our study, 83 men and 11 women had CA. We could not analyze whether our cases had multiple partners and a habit of condom use as some of the patients did not answer questions about their sexual life. We observed VDRL and TPHA positivity in 3 (3.1%) cases, none of those cases had clinical findings of syphilis and they denied using any therapy for syphilis. HBsAg positivity was found in 3 cases. No anti-HIV and anti-HCV antibody positivity was detected. CONCLUSIONS: The seroprevalence of HBsAg in our study was similar to that of the general population of Turkey. But as we found positive syphilis serology in 3 patients, we suggest that syphilis serology should be investigated in patients with CA. PMID- 26366154 TI - Prevalence of cardiovascular disease risk factors, and metabolic syndrome and its components in patients with psoriasis aged 30 to 49 years. AB - INTRODUCTION: Some studies show that metabolic syndrome (MS) is more common in psoriatic patients. AIM: To evaluate the prevalence of MS and its components as cardiovascular disease (CVD) risk factors in psoriatic patients compared to the general Polish population. MATERIAL AND METHODS: In 62 patients, aged 30 to 49 years with a mild to severe course of psoriasis, the features of MS have been assessed by IDF definition and compared to the results obtained in the NATPOL 2011 study. RESULTS: Analysis of CVD risk factors in patients with a severe course of psoriasis showed a correlation with waist circumference (0.38, p < 0.05), hypertension (0.40, p < 0.05) and a negative correlation with HDL (0.29, p < 0.05). The prevalence of MS in psoriatic patients was 25.81%, and for the control group - 21.02% (p > 0.05), the mean HOMA-IR was 1.93 and 1.94 (p > 0.05), respectively. There were differences in the prevalence of abdominal obesity (53.6% vs. 40.3%, p < 0.05). In lipid parameters, except for HDL, the compared groups did not differ significantly (triglycerides, ApoA-I and B). Criteria for MS concerning blood pressure (> 130/85 mm Hg) and hypertension were more frequent in men with psoriasis than in the control group (38.2% vs. 11.1%, p < 0.05). CONCLUSIONS: Severe psoriasis is associated with a significantly higher prevalence of risk factors for CVD. The prevalence of MS, insulin resistance and lipid abnormalities in patients with psoriasis aged 30 to 49 years is similar to the general Polish population. Abdominal obesity is more common in psoriatic patients and hypertension in men with psoriasis. PMID- 26366155 TI - Acne inversa: difficulties in diagnostics and therapy. AB - Acne inversa (hidradenitis suppurativa) is a potentially severe and chronic inflammatory disease with a significant negative influence on the quality of life. Usually, lesions are located in the areas of skin folds and it is characterized by the presence of painful nodules and fistulas with a tendency to tissue fibrosis. Currently, it is suggested that follicular occlusion by infundibular hyperkeratosis plays a crucial role in pathogenesis and an occupation of apocrine sweat glands is a secondary phenomenon. Most often, it refers to men after puberty. This article tries to present the latest theory concerning the etiology of inverted acne and methods of its treatment. It also describes the most common errors in diagnostic and therapeutic procedures, which are mainly connected with repeated and long antibiotic therapy and not radical surgical treatment. PMID- 26366156 TI - Tuberculosis of the oral cavity: an uncommon but still a live issue. AB - This paper aims at characterizing clinical features, occurrence, diagnostic process and treatment of oral tuberculosis (TB), basing on the available literature. Oral TB manifestations are uncommon and usually secondary to pulmonary changes. They predominantly appear as ulcers. Eruptions are usually single, painful and resistant to conventional treatment. Diagnosis always needs to be confirmed histopathologically. Anti-tubercular systemic therapy is required in every patient diagnosed with oral TB, while topical treatment is only adjuvant. A low incidence of oral TB together with a non-specific clinical picture might pose difficulties in its diagnosis. Oral changes in TB are likely to be overlooked what can result in further spread of Mycobacterium tuberculosis due to a delay in instituting proper treatment. Tuberculosis morbidity has risen recently and more multi-drug resistant strains of TB bacilli are found, what can result in a higher incidence of oral TB. Clinicians should be therefore aware of a possible occurrence of this entity and consider it while making a differential diagnosis of atypical oral changes. PMID- 26366157 TI - Coexistence of porokeratosis ptychotropica with porokeratosis of Mibelli in a Chinese man. PMID- 26366158 TI - A case of unilateral linear lichen planus: related to orthopedic prosthesis or not? PMID- 26366159 TI - Dermoscopy of nodular skin metastases from the gastrointestinal primary cancer. PMID- 26366160 TI - Seborrhoeic dermatitis and a herpes zoster infection developed during treatment with adalimumab due to Crohn's disease. PMID- 26366161 TI - Melanoma of unknown primary origin coexisting with early-onset multifocal basal cell carcinoma. PMID- 26366163 TI - Expected Utility Based Decision Making under Z-Information and Its Application. AB - Real-world decision relevant information is often partially reliable. The reasons are partial reliability of the source of information, misperceptions, psychological biases, incompetence, and so forth. Z-numbers based formalization of information (Z-information) represents a natural language (NL) based value of a variable of interest in line with the related NL based reliability. What is important is that Z-information not only is the most general representation of real-world imperfect information but also has the highest descriptive power from human perception point of view as compared to fuzzy number. In this study, we present an approach to decision making under Z-information based on direct computation over Z-numbers. This approach utilizes expected utility paradigm and is applied to a benchmark decision problem in the field of economics. PMID- 26366164 TI - Cuckoo Search Algorithm Based on Repeat-Cycle Asymptotic Self-Learning and Self Evolving Disturbance for Function Optimization. AB - In order to improve convergence velocity and optimization accuracy of the cuckoo search (CS) algorithm for solving the function optimization problems, a new improved cuckoo search algorithm based on the repeat-cycle asymptotic self learning and self-evolving disturbance (RC-SSCS) is proposed. A disturbance operation is added into the algorithm by constructing a disturbance factor to make a more careful and thorough search near the bird's nests location. In order to select a reasonable repeat-cycled disturbance number, a further study on the choice of disturbance times is made. Finally, six typical test functions are adopted to carry out simulation experiments, meanwhile, compare algorithms of this paper with two typical swarm intelligence algorithms particle swarm optimization (PSO) algorithm and artificial bee colony (ABC) algorithm. The results show that the improved cuckoo search algorithm has better convergence velocity and optimization accuracy. PMID- 26366165 TI - New Results on Passivity Analysis of Stochastic Neural Networks with Time-Varying Delay and Leakage Delay. AB - The passivity problem for a class of stochastic neural networks systems (SNNs) with varying delay and leakage delay has been further studied in this paper. By constructing a more effective Lyapunov functional, employing the free-weighting matrix approach, and combining with integral inequality technic and stochastic analysis theory, the delay-dependent conditions have been proposed such that SNNs are asymptotically stable with guaranteed performance. The time-varying delay is divided into several subintervals and two adjustable parameters are introduced; more information about time delay is utilised and less conservative results have been obtained. Examples are provided to illustrate the less conservatism of the proposed method and simulations are given to show the impact of leakage delay on stability of SNNs. PMID- 26366162 TI - Regulation of Hedgehog signaling by ubiquitination. AB - The Hedgehog (Hh) signaling pathway plays crucial roles both in embryonic development and in adult stem cell function. The timing, duration and location of Hh signaling activity need to be tightly controlled. Abnormalities of Hh signal transduction lead to birth defects or malignant tumors. Recent data point to ubiquitination-related posttranslational modifications of several key Hh pathway components as an important mechanism of regulation of the Hh pathway. Here we review how ubiquitination regulates the localization, stability and activity of the key Hh signaling components. PMID- 26366166 TI - An Analytical Framework for Runtime of a Class of Continuous Evolutionary Algorithms. AB - Although there have been many studies on the runtime of evolutionary algorithms in discrete optimization, relatively few theoretical results have been proposed on continuous optimization, such as evolutionary programming (EP). This paper proposes an analysis of the runtime of two EP algorithms based on Gaussian and Cauchy mutations, using an absorbing Markov chain. Given a constant variation, we calculate the runtime upper bound of special Gaussian mutation EP and Cauchy mutation EP. Our analysis reveals that the upper bounds are impacted by individual number, problem dimension number n, searching range, and the Lebesgue measure of the optimal neighborhood. Furthermore, we provide conditions whereby the average runtime of the considered EP can be no more than a polynomial of n. The condition is that the Lebesgue measure of the optimal neighborhood is larger than a combinatorial calculation of an exponential and the given polynomial of n. PMID- 26366168 TI - Phase Response Design of Recursive All-Pass Digital Filters Using a Modified PSO Algorithm. AB - This paper develops a new design scheme for the phase response of an all-pass recursive digital filter. A variant of particle swarm optimization (PSO) algorithm will be utilized for solving this kind of filter design problem. It is here called the modified PSO (MPSO) algorithm in which another adjusting factor is more introduced in the velocity updating formula of the algorithm in order to improve the searching ability. In the proposed method, all of the designed filter coefficients are firstly collected to be a parameter vector and this vector is regarded as a particle of the algorithm. The MPSO with a modified velocity formula will force all particles into moving toward the optimal or near optimal solution by minimizing some defined objective function of the optimization problem. To show the effectiveness of the proposed method, two different kinds of linear phase response design examples are illustrated and the general PSO algorithm is compared as well. The obtained results show that the MPSO is superior to the general PSO for the phase response design of digital recursive all-pass filter. PMID- 26366169 TI - Fuzzy Counter Propagation Neural Network Control for a Class of Nonlinear Dynamical Systems. AB - Fuzzy Counter Propagation Neural Network (FCPN) controller design is developed, for a class of nonlinear dynamical systems. In this process, the weight connecting between the instar and outstar, that is, input-hidden and hidden output layer, respectively, is adjusted by using Fuzzy Competitive Learning (FCL). FCL paradigm adopts the principle of learning, which is used to calculate Best Matched Node (BMN) which is proposed. This strategy offers a robust control of nonlinear dynamical systems. FCPN is compared with the existing network like Dynamic Network (DN) and Back Propagation Network (BPN) on the basis of Mean Absolute Error (MAE), Mean Square Error (MSE), Best Fit Rate (BFR), and so forth. It envisages that the proposed FCPN gives better results than DN and BPN. The effectiveness of the proposed FCPN algorithms is demonstrated through simulations of four nonlinear dynamical systems and multiple input and single output (MISO) and a single input and single output (SISO) gas furnace Box-Jenkins time series data. PMID- 26366167 TI - Effects of Between- and Within-Subject Variability on Autonomic Cardiorespiratory Activity during Sleep and Their Limitations on Sleep Staging: A Multilevel Analysis. AB - Autonomic cardiorespiratory activity changes across sleep stages. However, it is unknown to what extent it is affected by between- and within-subject variability during sleep. As it is hypothesized that the variability is caused by differences in subject demographics (age, gender, and body mass index), time, and physiology, we quantified these effects and investigated how they limit reliable cardiorespiratory-based sleep staging. Six representative parameters obtained from 165 overnight heartbeat and respiration recordings were analyzed. Multilevel models were used to evaluate the effects evoked by differences in sleep stages, demographics, time, and physiology between and within subjects. Results show that the between- and within-subject effects were found to be significant for each parameter. When adjusted by sleep stages, the effects in physiology between and within subjects explained more than 80% of total variance but the time and demographic effects explained less. If these effects are corrected, profound improvements in sleep staging can be observed. These results indicate that the differences in subject demographics, time, and physiology present significant effects on cardiorespiratory activity during sleep. The primary effects come from the physiological variability between and within subjects, markedly limiting the sleep staging performance. Efforts to diminish these effects will be the main challenge. PMID- 26366170 TI - Spirulina platensis Lacks Antitumor Effect against Solid Ehrlich Carcinoma in Female Mice. AB - Spirulina is a blue-green alga used as a dietary supplement. It has been shown to possess anti-inflammatory, antioxidant, and hepatoprotective properties. This study was designed to evaluate the antitumor effect of spirulina (200 and 800 mg/kg) against a murine model of solid Ehrlich carcinoma compared to a standard chemotherapeutic drug, 5-fluorouracil (20 mg/kg). Untreated mice developed a palpable solid tumor after 13 days. Unlike fluorouracil, spirulina at the investigated two dose levels failed to exert any protective effect. In addition, spirulina did not potentiate the antitumor effect of fluorouracil when they were administered concurrently. Interestingly, their combined administration resulted in a dose-dependent increase in mortality. The present study demonstrates that spirulina lacks antitumor effect against this model of solid Ehrlich carcinoma and increased mortality when combined with fluorouracil. However, the implicated mechanism is still elusive. PMID- 26366171 TI - Antihyperglycemic Activity of Eucalyptus tereticornis in Insulin-Resistant Cells and a Nutritional Model of Diabetic Mice. AB - Eucalyptus tereticornis is a plant used in traditional medicine to control diabetes, but this effect has not been proved scientifically. Here, we demonstrated through in vitro assays that E. tereticornis extracts increase glucose uptake and inhibit their production in insulin-resistant C2C12 and HepG2 cells, respectively. Furthermore, in a nutritional model using diabetic mice, the administration of ethyl acetate extract of E. tereticornis reduced fasting glycaemia, improved tolerance to glucose, and reduced resistance to insulin. Likewise, this extract had anti-inflammatory effects in adipose tissue when compared to control diabetic mice. Via bioguided assays and sequential purification of the crude extract, a triterpenoid-rich fraction from ethyl acetate extracts was shown to be responsible for the biological activity. Similarly, we identified the main compound responsible for the antihyperglycemic activity in this extract. This study shows that triterpenes found in E. tereticornis extracts act as hypoglycemic/antidiabetic compounds and contribute to the understanding of their use in traditional medicine. PMID- 26366172 TI - Effect of Repetitive Glucose Spike and Hypoglycaemia on Atherosclerosis and Death Rate in Apo E-Deficient Mice. AB - Epidemiological data suggest that postprandial hyperglycaemia and hypoglycaemia are potential risk factors for cardiovascular disease. However, the effects of repetitive postprandial glucose spikes, repetitive hypoglycaemia, and their combination on the progression of atherosclerosis remain largely unknown. The present study investigated the effects of rapid rises and falls in glucose, and their combination, on the progression of atherosclerosis in apolipoprotein (apo) E-deficient mice. In this study, apo E-deficient mice with forced oral administration of glucose twice daily for 15 weeks were used as a model of repetitive postprandial glucose spikes, and apo E-deficient mice given an intraperitoneal injection of insulin once a week for 15 weeks were used as a model of repetitive hypoglycaemia. In addition, we established a model of both repetitive postprandial glucose spikes and hypoglycaemia by combining the above interventions. Atherosclerosis was evaluated in all mice by oil red O staining. Administration of ipragliflozin, a selective inhibitor of sodium-glucose cotransporter 2, in the mouse model of repetitive glucose spikes inhibited the progression of atherosclerosis, whereas long-term repetitive glucose spikes, repetitive hypoglycaemia, and their combination had no significant impact on atherosclerosis. However, repetitive hypoglycaemia was associated with poor survival rate. The results showed that repetitive hypoglycaemia reduces the survival rate without associated progression of atherosclerosis in apo E deficient mice. PMID- 26366174 TI - Mechanisms of Normalisation of Bone Metabolism during Recovery from Hyperthyroidism: Potential Role for Sclerostin and Parathyroid Hormone. AB - Sclerostin, a protein expressed by osteocytes, is a negative regulator of bone formation. The aim of the study was to investigate the relationship between parathyroid hormone (PTH) and markers of bone metabolism and changes of sclerostin concentrations before and after treatment of hyperthyroidism. Patients and Methods. The study involved 33 patients (26 women), age (mean +/- SD) 48 +/- 15 years, with hyperthyroidism. Serum sclerostin, PTH, calcium, and bone markers [osteocalcin (OC) and collagen type I cross-linked C-telopeptide I (CTX)] were measured at diagnosis of hyperthyroidism and after treatment with thiamazole. Results. After treatment of hyperthyroidism a significant decrease in free T3 (FT3) and free T4 (FT4) concentrations was accompanied by marked decrease of serum sclerostin (from 43.7 +/- 29.3 to 28.1 +/- 18.4 pmol/L; p < 0.001), OC (from 35.6 +/- 22.0 to 27.0 +/- 14.3 ng/mL; p < 0.001), and CTX (from 0.49 +/- 0.35 to 0.35 +/- 0.23 ng/dL; p < 0.005), accompanied by an increase of PTH (from 29.3 +/- 14.9 to 39.8 +/- 19.8; p < 0.001). During hyperthyroidism there was a positive correlation between sclerostin and CTX (r s = 0.41, p < 0.05) and between OC and thyroid hormones (with FT3 r s = 0.42, with FT4 r s = 0.45, p < 0.05). Conclusions. Successful treatment of hyperthyroidism results in a significant decrease in serum sclerostin and bone markers concentrations, accompanied by an increase of PTH. PMID- 26366175 TI - Online NIR Analysis and Prediction Model for Synthesis Process of Ethyl 2 Chloropropionate. AB - Online near-infrared spectroscopy was used as a process analysis technique in the synthesis of 2-chloropropionate for the first time. Then, the partial least squares regression (PLSR) quantitative model of the product solution concentration was established and optimized. Correlation coefficient (R (2)) of partial least squares regression (PLSR) calibration model was 0.9944, and the root mean square error of correction (RMSEC) was 0.018105 mol/L. These values of PLSR and RMSEC could prove that the quantitative calibration model had good performance. Moreover, the root mean square error of prediction (RMSEP) of validation set was 0.036429 mol/L. The results were very similar to those of offline gas chromatographic analysis, which could prove the method was valid. PMID- 26366173 TI - Multiple Factors Related to the Secretion of Glucagon-Like Peptide-1. AB - The glucagon-like peptide-1 is secreted by intestinal L cells in response to nutrient ingestion. It regulates the secretion and sensitivity of insulin while suppressing glucagon secretion and decreasing postprandial glucose levels. It also improves beta-cell proliferation and prevents beta-cell apoptosis induced by cytotoxic agents. Additionally, glucagon-like peptide-1 delays gastric emptying and suppresses appetite. The impaired secretion of glucagon-like peptide-1 has negative influence on diabetes, hyperlipidemia, and insulin resistance related diseases. Thus, glucagon-like peptide-1-based therapies (glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors) are now well accepted in the management of type 2 diabetes. The levels of glucagon-like peptide-1 are influenced by multiple factors including a variety of nutrients. The component of a meal acts as potent stimulants of glucagon-like peptide-1 secretion. The levels of its secretion change with the intake of different nutrients. Some drugs also have influence on GLP-1 secretion. Bariatric surgery may improve metabolism through the action on GLP-1 levels. In recent years, there has been a great interest in developing effective methods to regulate glucagon-like peptide-1 secretion. This review summarizes the literature on glucagon-like peptide-1 and related factors affecting its levels. PMID- 26366176 TI - Risk Assessment and Prediction of Heavy Metal Pollution in Groundwater and River Sediment: A Case Study of a Typical Agricultural Irrigation Area in Northeast China. AB - The areas with typical municipal sewage discharge river and irrigation water function were selected as study sites in northeast China. The samples from groundwater and river sediment in this area were collected for the concentrations and forms of heavy metals (Cr(VI), Cd, As, and Pb) analysis. The risk assessment of heavy metal pollution was conducted based on single-factor pollution index (I) and Nemerow pollution index (NI). The results showed that only one groundwater sampling site reached a polluted level of heavy metals. There was a high potential ecological risk of Cd on the N21-2 sampling site in river sediment. The morphological analysis results of heavy metals in sediment showed that the release of heavy metals can be inferred as one of the main pollution sources of groundwater. In addition, the changes in the concentration and migration scope of As were predicted by using the Groundwater Modeling System (GMS). The predicted results showed that As will migrate downstream in the next decade, and the changing trend of As polluted areas was changed with As content districts because of some pump wells downstream to form groundwater depression cone, which made the solute transfer upstream. PMID- 26366177 TI - Comment on "The Role of Citrullinated Protein Antibodies in Predicting Erosive Disease in Rheumatoid Arthritis: A Systematic Literature Review and Meta Analysis". PMID- 26366179 TI - A Yoga Intervention for Posttraumatic Stress: A Preliminary Randomized Control Trial. AB - Yoga may be effective in the reduction of PTSD symptomology. The purpose of this study was to evaluate the impact of a Kundalini Yoga (KY) treatment on PTSD symptoms and overall wellbeing. To supplement the current field of inquiry, a pilot randomized control trial (RCT) was conducted comparing an 8-session KY intervention with a waitlist control group. 80 individuals with current PTSD symptoms participated. Both groups demonstrated changes in PTSD symptomology but yoga participants showed greater changes in measures of sleep, positive affect, perceived stress, anxiety, stress, and resilience. Between-groups effect sizes were small to moderate (0.09-0.25). KY may be an adjunctive or alternative intervention for PTSD. Findings indicate the need for further yoga research to better understand the mechanism of yoga in relation to mental and physical health, gender and ethnic comparisons, and short- and long-term yoga practice for psychiatric conditions. PMID- 26366178 TI - HLA-E: Presentation of a Broader Peptide Repertoire Impacts the Cellular Immune Response-Implications on HSCT Outcome. AB - The HLA-E locus encodes a nonclassical class Ib molecule that serves many immune functions from inhibiting NK cells to activating CTLs. Structural analysis of HLA E/NKG2A complexes visualized fine-tuning of protective immune responses through AA interactions between HLA-E, the bound peptide, and NKG2A/CD94. A loss of cellular protection through abrogation of the HLA-E/NKG2A engagement is dependent on the HLA-E bound peptide. The role of HLA-E in posttransplant outcomes is not well understood but might be attributed to its peptide repertoire. To investigate the self-peptide repertoire of HLA-E (*) 01:01 in the absence of protective HLA class I signal peptides, we utilized soluble HLA technology in class I negative LCL cells in order to characterize HLA-E (*) 01:01-bound ligands by mass spectrometry. To understand the immunological impact of these analyzed ligands on NK cell reactivity, we performed cellular assays. Synthesized peptides were loaded onto recombinant T2 cells expressing HLA-E (*) 01:01 molecules and applied in cytotoxicity assays using the leukemia derived NK cell line (NKL) as effector. HLA-E in complex with the self-peptides demonstrated a shift towards cytotoxicity and a loss of cell protection. Our data highlights the fact that the HLA-E peptidome is not as restricted as previously thought and support the suggestion of a posttransplant role for HLA-E. PMID- 26366180 TI - Intravenous Injections of Human Mesenchymal Stromal Cells Modulated the Redox State in a Rat Model of Radiation Myelopathy. AB - The main aim of the present study was to assess the antioxidative effects of human umbilical cord-derived mesenchymal stromal cells (UC-MSCs) in a rat model of radiation myelopathy. UC-MSCs were isolated from Wharton's jelly (WJ) of umbilical cords. An irradiated cervical spinal cord rat model (C2-T2 segment) was generated using a (60)Co irradiator to deliver 30 Gy of radiation. UC-MSCs were injected through the tail vein at 90 days, 97 days, 104 days, and 111 days after irradiation. Histological damage was examined by cresyl violet/Nissl staining. The activities of two antioxidant enzymes catalase (CAT) and glutathione peroxidase (GPX) in the spinal cord were measured by the biomedical assay. In addition, the levels of vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2) in the spinal cord were determined by ELISA methods. Multiple injections of UC-MSCs through the tail vein ameliorated neuronal damage in the spinal cord, increased the activities of the antioxidant enzymes CAT and GPX, and increased the levels of VEGF and Ang-2 in the spinal cord. Our results suggest that multiple injections of UC-MSCs via the tail vein in the rat model of radiation myelopathy could significantly improve the antioxidative microenvironment in vivo. PMID- 26366181 TI - Acupuncture to Treat Sleep Disorders in Postmenopausal Women: A Systematic Review. AB - Sleep disorders are commonly observed among postmenopausal women, with negative effects on their quality of life. The search for complementary therapies for sleep disorders during postmenopausal period is of high importance, and acupuncture stands out as an appropriate possibility. The present review intended to systematically evaluate the available literature, compiling studies that have employed acupuncture as treatment to sleep disorders in postmenopausal women. A bibliographic search was performed in PubMed/Medline and Scopus. Articles which had acupuncture as intervention, sleep related measurements as outcomes, and postmenopausal women as target population were included and evaluated according to the Cochrane risk of bias tool and to the STRICTA guidelines. Out of 89 search results, 12 articles composed our final sample. A high heterogeneity was observed among these articles, which prevented us from performing a meta-analysis. Selected articles did not present high risk of bias and had a satisfactory compliance rate with STRICTA guidelines. In general, these studies presented improvements in sleep-related variables. Despite the overall positive effects, acupuncture still cannot be stated as a reliable treatment for sleep-related complaints, not due to inefficacy, but rather limited evidence. Nevertheless, results are promising and new comprehensive and controlled studies in the field are encouraged. PMID- 26366182 TI - Effects of Electroacupuncture on Chronic Unpredictable Mild Stress Rats Depression-Like Behavior and Expression of p-ERK/ERK and p-P38/P38. AB - We investigate the antidepressant-like effect and mechanism of electroacupuncture (EA) on a chronic unpredictable mild stress rats depression-like behavior. In our study, depression in rats was induced by unpredictable chronic mild stress (UCMS) and isolation for four weeks. Male Sprague-Dawley rats were randomly divided into four groups: Normal, Model, EA, and Sham EA. EA treatment was administered for two weeks, once a day for five days a week. Two acupoints, Yintang (EX-HN3) and Baihui (GV20), were selected. For sham EA, acupuncture needles were inserted shallowly into the acupoints: EX-HN3 and GV20. No electrostimulator was connected. The antidepressant-like effect of the electroacupuncture treatment was measured by sucrose intake test, open field test, and forced swimming test in rats. The protein levels of phosphorylated extracellular regulated protein kinases (p-ERK1/2)/ERK1/2 and p-P38/P38 in the hippocampus (HP) were examined by Western blot analysis. Our data demonstrate that EA treatment decreased the immobility time of forced swimming test and improved the sucrose solution intake in comparison to unpredictable chronic mild stress and placebo sham control. Electroacupuncture may act on depression by enhancing p-ERK1/2 and p-p38 in the hippocampus. PMID- 26366183 TI - A Survey of Therapeutic Effects of Artemisia capillaris in Liver Diseases. AB - Artemisia capillaris has been recognized as an herb with therapeutic efficacy in liver diseases and widely used as an alternative therapy in Asia. Numerous studies have reported the antisteatotic, antioxidant, anti-inflammatory, choleretic, antiviral, antifibrotic, and antitumor activities of A. capillaris. These reports support its therapeutic potential in various liver diseases such as chronic hepatitis B virus (HBV) infection, cirrhosis, and hepatocellular carcinoma. In addition, several properties of its various constituents, which provide clues to the underlying mechanisms of its therapeutic effects, have been studied. This review describes the scientific evidence supporting the therapeutic potential of A. capillaris and its constituents in various liver diseases. PMID- 26366185 TI - A Novel Method for the Discrimination of Semen Arecae and Its Processed Products by Using Computer Vision, Electronic Nose, and Electronic Tongue. AB - Areca nut, commonly known locally as Semen Arecae (SA) in China, has been used as an important Chinese herbal medicine for thousands of years. The raw SA (RAW) is commonly processed by stir-baking to yellow (SBY), stir-baking to dark brown (SBD), and stir-baking to carbon dark (SBC) for different clinical uses. In our present investigation, intelligent sensory technologies consisting of computer vision (CV), electronic nose (E-nose), and electronic tongue (E-tongue) were employed in order to develop a novel and accurate method for discrimination of SA and its processed products. Firstly, the color parameters and electronic sensory responses of E-nose and E-tongue of the samples were determined, respectively. Then, indicative components including 5-hydroxymethyl furfural (5-HMF) and arecoline (ARE) were determined by HPLC. Finally, principal component analysis (PCA) and discriminant factor analysis (DFA) were performed. The results demonstrated that these three instruments can effectively discriminate SA and its processed products. 5-HMF and ARE can reflect the stir-baking degree of SA. Interestingly, the two components showed close correlations to the color parameters and sensory responses of E-nose and E-tongue. In conclusion, this novel method based on CV, E-nose, and E-tongue can be successfully used to discriminate SA and its processed products. PMID- 26366184 TI - Vitamin E Analogs as Radiation Response Modifiers. AB - The potentially life-threatening effects of total body ionizing radiation exposure have been known for more than a century. Despite considerable advances in our understanding of the effects of radiation over the past six decades, efforts to identify effective radiation countermeasures for use in case of a radiological/nuclear emergency have been largely unsuccessful. Vitamin E is known to have antioxidant properties capable of scavenging free radicals, which have critical roles in radiation injuries. Tocopherols and tocotrienols, vitamin E analogs together known as tocols, have shown promise as radioprotectors. Although the pivotal mechanisms of action of tocols have long been thought to be their antioxidant properties and free radical scavenging activities, other alternative mechanisms have been proposed to drive their activity as radioprotectors. Here we provide a brief overview of the effects of ionizing radiation, the mechanistic mediators of radiation-induced damage, and the need for radiation countermeasures. We further outline the role for, efficacy of, and mechanisms of action of tocols as radioprotectors, and we compare and contrast their efficacy and mode of action with that of another well-studied chemical radioprotector, amifostine. PMID- 26366188 TI - The relationship between defecation and feeding in nestling birds: observational and experimental evidence. AB - BACKGROUND: Adult birds clean the nest by consuming or transporting feces, which is thought to be important in order to lower the levels of parasites, pathogens and predation at the nest. If nestlings were to defecate when parents were absent, however, feces could accumulate in the nest. RESULTS: To understand the mechanism by which nest sanitation is maintained, we studied the timing of defecation in nestling birds of common passerine species in southwest China. In 159 nests of 8 species at the nestling stage during 779 randomly timed observations, we never found fecal sacs present. Video recordings, totaling 455 h at five Pycnonotus jocosus nests in the field, showed almost all defecation after feedings, and only nestlings that were fed defecated. Six translocated P. jocosus nests were taken into captivity in order to manipulate the frequency of feeding. These nestlings defecated only after feeding, even when feeding intervals were extended to 60 and 120 min. The fecal sac weight also increased with extended feeding intervals, demonstrating a remarkable plasticity for nestlings to wait for feedings. CONCLUSION: The evidence allows two major conclusions: 1) defecation in the nest occurs at a time that ensures nest sanitation, stimulated by feeding, rather than there being a set time of gut processing between feeding and excretion; 2) the strong plasticity in the timing of defecation and the possibility of negative repercussions (if defecation occurs when parents are absent) are important mechanisms underlying the efficiency of the feeding defecation system. PMID- 26366187 TI - Is a change in juvenile hormone sensitivity involved in range expansion in an invasive beetle? AB - INTRODUCTION: It has been suggested that rapid range expansion could proceed through evolution in the endocrinological machinery controlling life-history switches. Based on this we tested whether the Colorado potato beetle, Leptinotarsa decemlineata, which has rapidly expanded its range across latitudinal regions in Europe, and shows photoperiodic adaptation in overwintering initiation, has different sensitivities to juvenile hormone (JH) manipulation along a latitudinal gradient. RESULTS: A factorial experiment where beetles were reared either under a long or short day photoperiod was performed. Hormone levels were manipulated by topical applications. An allatostatin mimic, H17, was used to decrease and a juvenile hormone III analogue, pyriproxyfen, was used to increase the hormone levels. The effects of photoperiod and hormone manipulations on fecundity and overwintering related burrowing were monitored. Application of H17 decreased fecundity but did not induce overwintering related burrowing. Manipulation with pyriproxyfen increased fecundity and delayed burrowing. While small population-dependent differences in responsiveness to the topical application treatments were observed in fecundity, none were seen in overwintering related burrowing. CONCLUSIONS: The results indicate that the rapid photoperiodic adaptation manifested in several life-history and physiological traits in L. decemlineata in Europe is unlikely a result of population dependent differences in JH III sensitivity. While other endocrine factors cannot be ruled out, more likely mechanisms could be genetic changes in upstream elements, such as the photoperiodic clock or the insulin signaling pathway. PMID- 26366186 TI - The Effects of Elk Velvet Antler Dietary Supplementation on Physical Growth and Bone Development in Growing Rats. AB - Elk velvet antler (EVA) has been used in traditional Oriental medicine for centuries to promote general health; however, little evidence for its effect on bone development is available. We investigated the effects of lifelong exposure of Wistar rats to a diet containing 10% EVA on physical growth and bone development. Measurements included weekly body weights, blood chemistry and kidney and testis/ovary indices (sacrificed at 5, 9, or 16 weeks of age), and bone traits of the femur bones by peripheral quantitative computed tomography (pQCT). Mean body weights were higher in the EVA group at 4-8 weeks in males and at 5 weeks of age in females. The kidney indices were greater in EVA dietary supplemented male rats at 5 and 16 weeks of age, in females at 16 weeks of age, and testis/ovary indices at 5 weeks of age. The femoral length was increased in both males and females at 5 weeks, and several pQCT-measured parameters had increased in EVA males and females. The activity of alkaline phosphatase (ALP) increased in EVA group while the content of calcium and phosphorus did not differ among groups. Our results seem to support a role for dietary supplementation of EVA on growth and bone development in this model. PMID- 26366189 TI - Guidelines for measuring and reporting environmental parameters for experiments in greenhouses. AB - BACKGROUND: The importance of appropriate, accurate measurement and reporting of environmental parameters in plant sciences is a significant aspect of quality assurance for all researchers and their research. There is a clear need for ensuring research across the world can be compared, understood and where necessary replicated by fellow researchers. A common set of guidelines to educate, assist and encourage comparativeness is of great importance. On the other hand, the level of effort and attention to detail by an individual researcher should be commensurate with the particular research being conducted. For example, a researcher focusing on interactions of light and temperature should measure all relevant parameters and report a measurement summary that includes sufficient detail allowing for replication. Such detail may be less relevant when the impact of environmental parameters on plant growth and development is not the main research focus. However, it should be noted that the environmental experience of a plant during production can have significant impact when subsequent experiments investigate plants at a molecular, biochemical or genetic level or where species interactions are considered. Thus, researchers are encouraged to make a critical assessment of what parameters are of primary importance in their research and these parameters should be measured and reported. CONTENT: This paper brings together a collection of parameters that the authors, as members of International Committee on Controlled Environment Guidelines (ICCEG) in consultation with members of our three parent organizations, believe constitute those which should be recorded and reported when publishing scientific data from experiments in greenhouses. It provides recommendations to end users on when, how and where these parameters should be measured along with the appropriate internationally standardized units that should be used. PMID- 26366190 TI - Efficient Noninferiority Testing Procedures for Simultaneously Assessing Sensitivity and Specificity of Two Diagnostic Tests. AB - Sensitivity and specificity are often used to assess the performance of a diagnostic test with binary outcomes. Wald-type test statistics have been proposed for testing sensitivity and specificity individually. In the presence of a gold standard, simultaneous comparison between two diagnostic tests for noninferiority of sensitivity and specificity based on an asymptotic approach has been studied by Chen et al. (2003). However, the asymptotic approach may suffer from unsatisfactory type I error control as observed from many studies, especially in small to medium sample settings. In this paper, we compare three unconditional approaches for simultaneously testing sensitivity and specificity. They are approaches based on estimation, maximization, and a combination of estimation and maximization. Although the estimation approach does not guarantee type I error, it has satisfactory performance with regard to type I error control. The other two unconditional approaches are exact. The approach based on estimation and maximization is generally more powerful than the approach based on maximization. PMID- 26366191 TI - Comparisons of allometric and climate-derived estimates of tree coarse root carbon stocks in forests of the United States. AB - BACKGROUND: Refined estimation of carbon (C) stocks within forest ecosystems is a critical component of efforts to reduce greenhouse gas emissions and mitigate the effects of projected climate change through forest C management. Specifically, belowground C stocks are currently estimated in the United States' national greenhouse gas inventory (US NGHGI) using nationally consistent species- and diameter-specific equations applied to individual trees. Recent scientific evidence has pointed to the importance of climate as a driver of belowground C stocks. This study estimates belowground C using current methods applied in the US NGHGI and describes a new approach for merging both allometric models with climate-derived predictions of belowground C stocks. RESULTS: Climate-adjusted predictions were variable depending on the region and forest type of interest, but represented an increase of 368.87 Tg of belowground C across the US, or a 6.4 % increase when compared to currently-implemented NGHGI estimates. Random forests regressions indicated that aboveground biomass, stand age, and stand origin (i.e., planted versus artificial regeneration) were useful predictors of belowground C stocks. Decreases in belowground C stocks were modeled after projecting mean annual temperatures at various locations throughout the US up to year 2090. CONCLUSIONS: By combining allometric equations with trends in temperature, we conclude that climate variables can be used to adjust the US NGHGI estimates of belowground C stocks. Such strategies can be used to determine the effects of future global change scenarios within a C accounting framework. PMID- 26366192 TI - Prevalence and Predictors of Complementary and Alternative Medicine Use in a Large Insured Sample of Children with Autism Spectrum Disorders. AB - PURPOSE: The purpose of the present study was to examine the prevalence and predictors of complementary and alternative medicine (CAM) use as well as parental perceptions of CAM efficacy in a large, geographically diverse sample of children with Autism Spectrum Disorders (ASD). METHODOLOGY: Data were obtained from a web-based survey administered to parents of children with ASD at four sites participating in the Mental Health Research Network (MHRN). The web survey obtained information about services and treatments received by children with ASD as well as the caregivers' experiences with having a child with ASD. RESULTS: Approximately 88% of the sample had either used CAM in the past or had recently used some type of CAM. The following characteristics were associated with CAM use: greater parental education, younger child age, a mix of regular and special classroom settings and prescription drug use in the past three months. CONCLUSIONS: The use of CAM was very prevalent in this large, geographically diverse sample of children with ASD. It is critical that providers be prepared to discuss the advantages and potential side effects with families to help them make well-informed health care decisions and prevent possible CAM-drug interactions. PMID- 26366193 TI - Tailoring interventions to implement recommendations for the treatment of elderly patients with depression: a qualitative study. AB - BACKGROUND: To improve adherence to evidence-based recommendations, it is logical to identify determinants of practice and tailor interventions to address these. We have previously prioritised six recommendations to improve treatment of elderly patients with depression, and identified determinants of adherence to these recommendations. The aim of this article is to describe how we tailored interventions to address the determinants for the implementation of the recommendations. METHODS: We drafted an intervention plan, based on the determinants we had identified in a previous study. We conducted six group interviews with representatives of health professionals (GPs and nurses), implementation researchers, quality improvement officers, professional and voluntary organisations and relatives of elderly patients with depression. We informed about the gap between evidence and practice for elderly patients with depression and presented the prioritised determinants that applied to each recommendation. Participants brainstormed individually and then in groups, suggesting interventions to address the determinants. We then presented evidence on the effectiveness of strategies for implementing depression guidelines. We asked the groups to prioritise the suggested interventions considering the perceived impact of determinants and of interventions, the research evidence underlying the interventions, feasibility and cost. We audiotaped and transcribed the interviews and applied a five step framework for our analysis. We created a logic model with links between the determinants, the interventions, and the targeted improvements in adherence. RESULTS: Six groups with 29 individuals provided 379 suggestions for interventions. Most suggestions could be fit within the drafted plan, but the groups provided important amendments or additions. We sorted the interventions into six categories: resources for municipalities to develop a collaborative care plan, resources for health professionals, resources for patients and their relatives, outreach visits, educational and web-based tools. Some interventions addressed one determinant, while other interventions addressed several determinants. CONCLUSIONS: It was feasible and helpful to use group interviews and combine open and structured approaches to identify interventions that addressed prioritised determinants to adherence to the recommendations. This approach generated a large number of suggested interventions. We had to prioritise to tailor the interventions strategies. PMID- 26366196 TI - Indirect evolutionary rescue: prey adapts, predator avoids extinction. AB - Recent studies have increasingly recognized evolutionary rescue (adaptive evolution that prevents extinction following environmental change) as an important process in evolutionary biology and conservation science. Researchers have concentrated on single species living in isolation, but populations in nature exist within communities of interacting species, so evolutionary rescue should also be investigated in a multispecies context. We argue that the persistence or extinction of a focal species can be determined solely by evolutionary change in an interacting species. We demonstrate that prey adaptive evolution can prevent predator extinction in two-species predator-prey models, and we derive the conditions under which this indirect evolutionary interaction is essential to prevent extinction following environmental change. A nonevolving predator can be rescued from extinction by adaptive evolution of its prey due to a trade-off for the prey between defense against predation and population growth rate. As prey typically have larger populations and shorter generations than their predators, prey evolution can be rapid and have profound effects on predator population dynamics. We suggest that this process, which we term 'indirect evolutionary rescue', has the potential to be critically important to the ecological and evolutionary responses of populations and communities to dramatic environmental change. PMID- 26366195 TI - Using neutral, selected, and hitchhiker loci to assess connectivity of marine populations in the genomic era. AB - Estimating the rate of exchange of individuals among populations is a central concern to evolutionary ecology and its applications to conservation and management. For instance, the efficiency of protected areas in sustaining locally endangered populations and ecosystems depends on reserve network connectivity. The population genetics theory offers a powerful framework for estimating dispersal distances and migration rates from molecular data. In the marine realm, however, decades of molecular studies have met limited success in inferring genetic connectivity, due to the frequent lack of spatial genetic structure in species exhibiting high fecundity and dispersal capabilities. This is especially true within biogeographic regions bounded by well-known hotspots of genetic differentiation. Here, we provide an overview of the current methods for estimating genetic connectivity using molecular markers and propose several directions for improving existing approaches using large population genomic datasets. We highlight several issues that limit the effectiveness of methods based on neutral markers when there is virtually no genetic differentiation among samples. We then focus on alternative methods based on markers influenced by selection. Although some of these methodologies are still underexplored, our aim was to stimulate new research to test how broadly they are applicable to nonmodel marine species. We argue that the increased ability to apply the concepts of cline analyses will improve dispersal inferences across physical and ecological barriers that reduce connectivity locally. We finally present how neutral markers hitchhiking with selected loci can also provide information about connectivity patterns within apparently well-mixed biogeographic regions. We contend that one of the most promising applications of population genomics is the use of outlier loci to delineate relevant conservation units and related eco-geographic features across which connectivity can be measured. PMID- 26366194 TI - Wolbachia strains for disease control: ecological and evolutionary considerations. AB - Wolbachia are endosymbionts found in many insects with the potential to suppress vectorborne diseases, particularly through interfering with pathogen transmission. Wolbachia strains are highly variable in their effects on hosts, raising the issue of which attributes should be selected to ensure that the best strains are developed for disease control. This depends on their ability to suppress viral transmission, invade host populations, persist without loss of viral suppression and not interfere with other control strategies. The potential to achieve these objectives is likely to involve evolutionary constraints; viral suppression may be limited by the ability of infections to spread due to deleterious host fitness effects. However, there are exceptions to these patterns in both natural infections and in novel associations generated following interspecific transfer, suggesting that pathogen blockage, deleterious fitness effects and changes to reproductive biology might be at least partly decoupled to achieve ideal infection attributes. The stability of introduced Wolbachia and its effects on viral transmission remain unclear, but rapid evolutionary changes seem unlikely. Although deliberate transfers of Wolbachia across species remain particularly challenging, the availability of strains with desirable attributes should be expanded, taking advantage of the diversity available across thousands of strains in natural populations. PMID- 26366197 TI - Determinants of male floating behaviour and floater reproduction in a threatened population of the hihi (Notiomystis cincta). AB - Floating males are usually thought of as nonbreeders. However, some floating individuals are able to reproduce through extra-pair copulations. Floater reproductive success can impact breeders' sex ratio, reproductive variance, multiple paternity and inbreeding, particularly in small populations. Changes in reproductive variance alter the rate of genetic drift and loss of genetic diversity. Therefore, genetic management of threatened species requires an understanding of floater reproduction and determinants of floating behaviour to effectively conserve species. Here, we used a pedigreed, free-living population of the endangered New Zealand hihi (Notiomystis cincta) to assess variance in male reproductive success and test the genetic (inbreeding and heritability) and conditional (age and size) factors that influence floater behaviour and reproduction. Floater reproduction is common in this species. However, floater individuals have lower reproductive success and variance in reproductive success than territorial males (total and extra-pair fledglings), so their relative impact on the population's reproductive performance is low. Whether an individual becomes a floater, and if so then how successful they are, is determined mainly by individual age (young and old) and to lesser extents male size (small) and inbreeding level (inbred). Floating males have a small, but important role in population reproduction and persistence of threatened populations. PMID- 26366198 TI - Ongoing ecological speciation in Cotesia sesamiae, a biological control agent of cereal stem borers. AB - To develop efficient and safe biological control, we need to reliably identify natural enemy species, determine their host range, and understand the mechanisms that drive host range evolution. We investigated these points in Cotesia sesamiae, an African parasitic wasp of cereal stem borers. Phylogenetic analyses of 74 individual wasps, based on six mitochondrial and nuclear genes, revealed three lineages. We then investigated the ecological status (host plant and host insect ranges in the field, and host insect suitability tests) and the biological status (cross-mating tests) of the three lineages. We found that one highly supported lineage showed all the hallmarks of a cryptic species. It is associated with one host insect, Sesamia nonagrioides, and is reproductively isolated from the other two lineages by pre- and postmating barriers. The other two lineages had a more variable phylogenetic support, depending on the set of genes; they exhibited an overlapping and diversified range of host species and are not reproductively isolated from one another. We discuss the ecological conditions and mechanisms that likely generated this ongoing speciation and the relevance of this new specialist taxon in the genus Cotesia for biological control. PMID- 26366199 TI - The geographic mosaic of herbicide resistance evolution in the common morning glory, Ipomoea purpurea: Evidence for resistance hotspots and low genetic differentiation across the landscape. AB - Strong human-mediated selection via herbicide application in agroecosystems has repeatedly led to the evolution of resistance in weedy plants. Although resistance can occur among separate populations of a species across the landscape, the spatial scale of resistance in many weeds is often left unexamined. We assessed the potential that resistance to the herbicide glyphosate in the agricultural weed Ipomoea purpurea has evolved independently multiple times across its North American range. We examined both adaptive and neutral genetic variations in 44 populations of I. purpurea by pairing a replicated dose response greenhouse experiment with SSR genotyping of experimental individuals. We uncovered a mosaic pattern of resistance across the landscape, with some populations exhibiting high-survival postherbicide and other populations showing high death. SSR genotyping revealed little evidence of isolation by distance and very little neutral genetic structure associated with geography. An approximate Bayesian computation (ABC) analysis uncovered evidence for migration and admixture among populations before the widespread use of glyphosate rather than the very recent contemporary gene flow. The pattern of adaptive and neutral genetic variations indicates that resistance in this mixed-mating weed species appears to have evolved in independent hotspots rather than through transmission of resistance alleles across the landscape. PMID- 26366200 TI - Hybridization and the spread of the apple maggot fly, Rhagoletis pomonella (Diptera: Tephritidae), in the northwestern United States. AB - Hybridization may be an important process interjecting variation into insect populations enabling host plant shifts and the origin of new economic pests. Here, we examine whether hybridization between the native snowberry-infesting fruit fly Rhagoletis zephyria (Snow) and the introduced quarantine pest R. pomonella (Walsh) is occurring and may aid the spread of the latter into more arid commercial apple-growing regions of central Washington state, USA. Results for 19 microsatellites implied hybridization occurring at a rate of 1.44% per generation between the species. However, there was no evidence for increased hybridization in central Washington. Allele frequencies for seven microsatellites in R. pomonella were more 'R. zephyria-like' in central Washington, suggesting that genes conferring resistance to desiccation may be adaptively introgressing from R. zephyria. However, in only one case was the putatively introgressing allele from R. zephyria not found in R. pomonella in the eastern USA. Thus, many of the alleles changing in frequency may have been prestanding in the introduced R. pomonella population. The dynamics of hybridization are therefore complex and nuanced for R. pomonella, with various causes and factors, including introgression for a portion, but not all of the genome, potentially contributing to the pest insect's spread. PMID- 26366202 TI - Patient perceptions of foot disability in Juvenile Idiopathic Arthritis: a comparison of the juvenile arthritis foot disability index and the Oxford ankle foot questionnaire for children. AB - BACKGROUND: The Juvenile Arthritis Foot Disability Index (JAFI) and the Oxford Ankle Foot Questionnaire for Children (OxAFQ-C) are two region-specific paediatric outcome tools that measure the impact on well-being in children with foot pathology. The aim of this study was to establish the level of agreement between the JAFI and the OxAFQ-C in a group of children diagnosed with Juvenile Idiopathic Arthritis (JIA). METHODS: Children with JIA accessed the questionnaire via a website. The OxAFQ-C questionnaire and the JAFI questionnaire were combined into one document consisting of 42 statements with Likert-scale responses. A further question regarding duration of disease was added. On completion, the web linked questionnaire was returned by e-mail. RESULTS: Thirty five participants were included. Individual domain and composite score analysis was undertaken. The JAFI participation domain was compared to the OxAFQ-C school domain and showed no significant difference between the median scores of each participant (z = -1.33, p = 0.181). The JAFI activity and the OxAFQ-C physical domains were compared and showed that a significant difference between the median scores existed (z = 4.29, p < 0.001). Agreement between the two PROMs was tested using Bland Altman Levels of Agreement based upon the percentage summed composite scores. Levels of agreement between the scores were considered to be poor based on the Bland Altman plot, despite a low mean difference in scores (mean difference = -3.88, SD of difference = 9.93, p = 0.027). Pearson correlation was undertaken to measure the relationship between the summed composite score and disease duration. No relationship was found (JAFI: r = -0.08, p = 0.672; OxAFQ-C: r = 0.037, p = 0.871). CONCLUSIONS: This study has shown that despite some agreement between the individual domains, overall there is poor agreement between the OxAFQ-C and the JAFI percentage summed composite scores. The study is not able to determine if one score is superior to the other but both scores could be of value when used in this population. PMID- 26366203 TI - Foot orthoses for the prevention of lower limb overuse injuries in naval recruits: study protocol for a randomised controlled trial. AB - BACKGROUND: Foot orthoses are frequently used for the prevention of lower limb overuse injuries but evidence for their effectiveness is limited. The primary aim of this study is to determine if prefabricated foot orthoses reduce the incidence of lower limb overuse injuries in naval recruits undertaking 11 weeks of basic training. METHODS: This study is a participant and assessor blinded, parallel group, randomised controlled trial. The trial will recruit participants undertaking 11 weeks of basic training at the Royal Australian Navy Recruit School, Cerberus, Victoria, Australia. Participants will be randomised to a control group (flat insole) or an intervention group (prefabricated foot orthosis). Over the 11 weeks of basic training, participants will document the presence and location of pain in weekly self-report diaries. The end-point for each participant will be the completion of 11 weeks of basic training. The primary outcome measure will be the combined incidence of four lower limb injuries (medial tibial stress syndrome, patellofemoral pain, Achilles tendinopathy, and plantar fasciitis/plantar heel pain) which are common among defence members. Secondary outcome measures include: (i) overall incidence of lower limb pain, (ii) severity of lower limb pain, (iii) time to injury, (iv) time to drop-out due to injury, (v) adverse events, (vi) number of lost training days, (vii) shoe comfort, and (viii) general health status. Data will be analysed using the intention-to-treat principle. DISCUSSION: This randomised controlled trial will evaluate the effectiveness of prefabricated foot orthoses for the prevention of common lower limb overuse injuries in naval recruits. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12615000024549. PMID- 26366204 TI - Diagnostic performance analysis for diabetic cardiovascular autonomic neuropathy based on short-term heart rate variability using Bayesian methods: preliminary analysis. AB - OBJECTIVES: This study aimed to estimate the performance of diabetic cardiovascular autonomic neuropathy (DCAN) diagnostic tests in the absence of a gold standard. BACKGROUND: The DCAN prevalence is rapidly growing in all populations worldwide. No document has been reported about diagnostic performance for DCAN based on short-term HRV without a gold standard. METHODS: We conducted a cross-sectional study to perform diagnostic test in Chinese diabetic patients. A dataset contained 56 subjects who completed both the short-term HRV test and Ewing's test. Simultaneous inferences about the population prevalence and the performance of each diagnostic test were possible using the Bayesian approach. RESULTS: The HRV test had a high sensitivity (0.837 and 0.821 for independence model) and specificity (0.838 and 0.797 for dependence model) to DCAN. In addition, the non-inferiority test rejected the hypothesis that the performance of the HRV test was inferior to that of Ewing's test (P < 0.05). The estimated DCAN prevalence in our study sample was more than 0.400. CONCLUSION: Our findings provided evidence that short-term HRV were used for the DCAN diagnostic test with a high sensitivity and specificity. ClinicalTrial.org ID: NCT02461381. PMID- 26366205 TI - Probiotic B420 and prebiotic polydextrose improve efficacy of antidiabetic drugs in mice. AB - BACKGROUND: Gut microbiota is now known to control glucose metabolism. Previous studies have shown that probiotics and prebiotics may improve glucose metabolism, but their effects have not been studied in combination with drug therapy. The aim of this study was to investigate whether probiotics and prebiotics combined with drug therapy affect diabetic outcomes. METHODS: Two different study designs were used to test gut microbiota modulating treatments with metformin (MET) or sitagliptin (SITA) in male C57Bl/6J mice. In Design 1, diabetes was induced with four-week feeding with a ketogenic, 72 kcal% fat diet with virtually no carbohydrates. Mice were then randomly divided into four groups (n = 10 in each group): (1) vehicle, (2) Bifidobacterium animalis ssp. lactis 420 (B420) (10(9) CFU/day), (3) MET (2 mg/mL in drinking water), or (4) MET + B420 (same doses as in the MET and B420 groups). After another 4 weeks, glucose metabolism was assessed with a glucose tolerance test. Fasting glucose, fasting insulin and HOMA IR were also assessed. In Design 2, mice were fed the same 72 kcal% fat diet to induce diabetes, but they were simultaneously treated within their respective groups (n = 8 in each group): (1) non-diabetic healthy control, (2) vehicle, (3) SITA [3 mg/(kg*day)] (4) SITA with prebiotic polydextrose (PDX) (0.25 g/day), (5) SITA with B420 (10(9) CFU/day), and (6) SITA + PDX + B420. Glucose metabolism was assessed at 4 weeks, and weight development was monitored for 6 weeks. RESULTS: In Design 1, with low-dose metformin, mice treated with B420 had a significantly lower glycemic response (area under the curve) (factorial experiment, P = 0.002) and plasma glucose concentration (P = 0.02) compared to mice not treated with B420. In Design 2, SITA + PDX reduced glycaemia in the oral glucose tolerance test significantly more than SITA only (area under the curve reduced 28 %, P < 0.0001). In addition, B420, PDX or B420+PDX, together with SITA, further decreased fasting glucose concentrations compared to SITA only (-19.5, -40 and 49 %, respectively, P < 0.01 for each comparison). The effect of PDX may be due to its ability to increase portal vein GLP-1 concentrations together with SITA (P = 0.0001 compared to vehicle) whereas SITA alone had no statistically significant effect compared to vehicle (P = 0.14). CONCLUSIONS: This study proposes that combining probiotics and/or prebiotics with antidiabetic drugs improves glycemic control and insulin sensitivity in mice. Mechanisms could be related to incretin secretion. PMID- 26366206 TI - Young children's knowledge about the spatial layout of writing. AB - Children who are knowledgeable about the basic properties of writing when formal literacy instruction begins are better prepared to benefit from that instruction than children who know less about this topic. In the present study, we examined U.S. preschoolers' knowledge about one aspect of writing: its spatial arrangement. Our participants, who had a mean age of 4 years, 2 months and who could not read any words in a list of simple words, were significantly above the level of chance at determining that horizontally arranged strings of letters are more like the writing in books than are letters with vertical, diagonal, or scattered arrangements. Contrary to the theory that children learn about the characteristics of writing that hold true in all writing systems before they learn about the characteristics that are specific to their own writing system, young children did not show a priority for vertical arrangements. The results are more consistent with the hypothesis that preschoolers apply their statistical learning skills to the spatial layout of writing. PMID- 26366207 TI - Quantifying Aptamer-Protein Binding via Thermofluorimetric Analysis. AB - Effective aptamer-based protein assays require coupling to a quantitative reporter of aptamer-protein binding. Typically, this involves a direct optical or electrochemical readout of DNA hybridization or an amplification step coupled to the readout. However, method development is often hampered by the multiplicity of aptamer-target binding mechanisms, which can interfere with the hybridization step. As a simpler and more generalizable readout of aptamer-protein binding, we report that thermofluorimetric analysis (TFA) can be used to quantitatively assay protein levels. Sub-nanomolar detection (0.74 nM) of platelet-derived growth factor (PDGF) with its corresponding aptamer is shown as a test case. In the presence of various DNA intercalating dyes, protein-bound aptamers exhibit a change in fluorescence intensity compared to the intercalated, unbound aptamer. This allows thermal resolution of bound and unbound aptamers using fluorescence melting analysis (-dF/dT curves). Remarkably, the homogeneous optical method allows subtraction of autofluorescence in human serum, giving PDGF detection limits of 1.8 and 10.7 nM in serum diluted 1:7 and 1:3, respectively. We have thus demonstrated that bound and unbound aptamers can be thermally resolved in a homogeneous format using a simple qPCR instrument-even in human serum. The simplicity of this approach provides an important step toward a robust, generalizable readout of aptamer-protein binding. PMID- 26366208 TI - WWTR1 (WW domain containing transcription regulator 1). AB - WWTR1 (also called TAZ in publications. Therefore, TAZ is used in the following description) is a WW domaing-containing transcriptional coactivator, which was first identified as a 14-3-3 binding protein. TAZ is the downstream component in the Hippo pathway, and also has been found to interact with different pathways, such as Wnt, TGFbeta, etc. TAZ is involved in mesenchymal stem cell differentiation as well as tumorigenesis. High level of TAZ has been found in different cancers, such as breast cancer, colon cancer, lung cancer, etc. PMID- 26366209 TI - Tissue-Specific Metabolic Profile Study of Moringa oleifera L. Using Nuclear Magnetic Resonance Spectroscopy. AB - Moringa oleifera, an important multipurpose crop, is rich in various phytochemicals: flavonoids, antioxidants, vitamins, minerals and carotenes. The purpose of this study was to profile the groups of metabolites in leaf and stem tissues of M. oleifera. Various sugars, amino acids, and organic acid derivatives were found in all of the M. oleifera tissues with different profiles/peak intensities depending on the tissue. 1D proton nuclear magnetic resonance (NMR) was applied for collecting metabolite spectra. Approximately 30 metabolites with 2 unknown peaks were identified with Chenomx and verified with MMCD databases using carbon data. Among these metabolites, 22 metabolites were identified as common in both leaf and stem tissues. Of the remaining 8 metabolites, 4 aminobutyrate, adenosine, guanosine, tyrosine, and p-cresol were found only in leaf tissues; however, glutamate, glutamine, and tryptophan were found only in stem tissues. Biochemical pathway analysis revealed that 28 identified metabolites were interconnected with 36 different pathways as well as related to different fatty acids and secondary metabolites synthesis biochemical pathways. It is well known that different tissues of M. oleifera have nutritional, medicinal, and therapeutic values; therefore, our main objective is to provide a publicly available M. oliefera tissue specific metabolite database. PMID- 26366210 TI - Bioimpedance Detection of Oral Lichen Planus Used as Preneoplastic Model. AB - INTRODUCTION: Bioimpedance is a measure of the electrical properties of biological tissues. In the last two decades bioimpedance has been successfully introduced in clinical diagnosis of cancer. It has been demonstrated that tumoral tissues often show lower bioimpedance values than healthy tissues. The aim of this work is to assess the bioimpedentiometric differences between healthy and Oral Lichen Planus (OLP) affected oral mucosa, taking attention to the erosive form which may represent a potential pre-cancerous condition. METHODS: 52 patients affected by OLP were recruited for bioimpedance examination of oral mucosa. Four electrical properties, resistance (R), reactance (Xc), phase angle (theta) and impedance (Z) of the tongue and of the intraoral mucosa, were measured. RESULTS: We observed a significant increase of Z and a significant decrease of theta values in correspondence of OLP lesions compared to healthy oral mucosa, and a marked decrease of Z values in correspondence of erosive OLP lesions. CONCLUSIONS: These results provide evidence of the usefulness of bioimpedance assay for the characterization of healthy and clinically OLP affected mucosa. Bioimpedance is a valid aid in the early detection and clinical monitoring of the suspicious lesions which could lead to a potentially malignant evolution. The present research article is a valuable addition to the scientific literature of cancer prevention, and our findings can be considered extremely encouraging as they represent the initial step for a more wide clinical study for better define the different cut-off values in the different precancerous conditions occurring in the oral mucosa. PMID- 26366211 TI - Mutation Analysis of Nine Chordoma Specimens by Targeted Next-Generation Cancer Panel Sequencing. AB - BACKGROUND: Chordoma is a rare primary malignant bone tumour. Treatment options are mainly restricted to surgical excision, since chordomas are largely resistant to conventional ionising radiation and chemotherapy. Thus, there is a strong need to gain more thorough insights into the molecular biology and genetics of chordoma to allow for the development of new therapeutic options. We performed an ultra-deep sequencing analysis to find novel mutations in cancer associated genes in chordomas to date unseen with Sanger sequencing. MATERIAL AND METHODS: Nine chordomas (skull base (n=3), mobile spine (n=4), and sacrum/coccyx (n=2) were screened for mutations in 48 cancer genes using the Hot Spot Cancer Panel (Illumina). All putative mutations were compared against multiple databases (e.g. NCBI, COSMIC, PolyPhen, EGB, SIFT) and published Copy Number Variation (CNV) data for chordoma. RESULTS: Our results showed mutations with a frequency above 5% in tumorsuppressor- and onco-genes, revealing new possible driver genes for chordomas. We detected three different variants accounting for 11 point mutations in three cancer associated genes (KIT, KDR and TP53). None of the detected mutations was found in all samples investigated. However, all genes affected interact or are connected in pathway analysis. There were no correlations to already reported CNVs in the samples analysed. CONCLUSIONS: We identified mutations in the associated genes KIT, KDR, and TP53. These mutations have been described previously and have been predicted to be tolerated. Further results on a larger series are warranted. The driver mechanisms of chordoma still have to be identified. PMID- 26366212 TI - Increased Expression of Eps15 Homology Domain 1 is Associated with Poor Prognosis in Resected Small Cell Lung Cancer. AB - One of the great challenges of small cell lung cancer (SCLC) treatment is identifying patients at high risk for recurrence after surgical resection and chemotherapy. We examined Eps15 homology domain 1 (EHD1) protein expression in paraffin sections of 85 resected SCLC tissues, metastatic lymph nodes and normal bronchial epithelial tissues using immunohistochemistry to study the correlation between EHD1 expression and patient clinicopathological features. Within these variables, disease free survival (DFS) analyzed by the log-rank test was constructed using the multivariate Cox proportional hazards regression model and Kaplan-Meier analysis. Immunohistochemistry results showed that EHD1 protein was significantly increased in SCLC tissues compared with normal tissues (P < 0.001). Moreover, EHD1 expression was positively correlated with tumor size (P = 0.019). Multivariate Cox proportional hazards model analysis showed that EHD1 expression (P = 0.047; HR, 1.869; 95% CI, 1.008-3.466) and American Joint Committee on Cancer (AJCC) status (P < 0.001; HR, 1.412; 95% CI, 1.165-1.711) were independent prognostic indicators of DFS. In conclusion, these data demonstrated a remarkable correlation between the cytoplasmic expression of EHD1 protein and adverse prognosis in patients receiving early-stage cisplatin treatment for resected SCLC. PMID- 26366213 TI - The Histone Deacetylase Inhibitor Vaproic Acid Induces Cell Growth Arrest in Hepatocellular Carcinoma Cells via Suppressing Notch Signaling. AB - Hepatocellular carcinoma (HCC) is a type of malignant cancer. Notch signaling is aberrantly expressed in HCC tissues with more evidence showing that this signaling plays a critical role in HCCs. In the present study, we investigate the effects of the anti-convulsant drug valproic acid (VPA) in HCC cells and its involvement in modulating Notch signaling. We found that VPA, acting as a histone deacetylase (HDAC) inhibitor, induced a decrease in HDAC4 and an increase in acetylated histone 4 (AcH4) and suppressed HCC cell growth. VPA also induced down regulation of Notch signaling via suppressing the expression of Notch1 and its target gene HES1, with an increase of tumor suppressor p21 and p63. Furthermore, Notch1 activation via overexpressing Notch1 active form ICN1 induced HCC cell proliferation and anti-apoptosis, indicating Notch signaling played an oncogenic role in HCC cells. Meanwhile, VPA could reverse Notch1-induced increase of cell proliferation. Interestingly, VPA was also observed to stimulate the expression of G protein-coupled somatostatin receptor type 2 (SSTR2) that has been used in receptor-targeting therapies. This discovery supports a combination therapy of VPA with the SSTR2-targeting agents. Our in vitro assay did show that the combination of VPA and the peptide-drug conjugate camptothecin-somatostatin (CPT SST) displayed more potent anti-proliferative effects on HCC cells than did each alone. VPA may be a potential drug candidate in the development of anti-HCC drugs via targeting Notch signaling, especially in combination with receptor-targeting cytotoxic agents. PMID- 26366214 TI - Akt and Hippo Pathways in Ewing's Sarcoma Tumors and Their Prognostic Significance. AB - BACKGROUND: Ewing's sarcoma tumor is an aggressive malignancy of bone and soft tissue in children and young adults. Despite advances in modern therapy, metastasis occurs and results in high mortality. Intracellular molecules Yap, Akt, mTOR, and Erk are signaling pathway members that regulate the proliferation of tumor cells. OBJECTIVE AND METHODS: We studied the immunohistochemical expression of these proteins in 36 tumor samples from adult and pediatric patients with Ewing's sarcoma tumors. Patients' age, sex, tumor site, tumor size, clinical stage and survival (overall and disease-free survival) were collected. Tissue microarrays slides were stained with antibodies against Yap, Akt, mTOR, and Erk proteins. RESULTS: Tumors exhibited variable expression of Yap, Akt, mTOR, and Erk (from negative, low to high), with high levels of expression present in 31%, 53%, 77% and 0% respectively. Immunohistochemical expression of Akt was associated with worse overall and disease-free survival (p<0.05). The other biomarkers did not demonstrate any difference in survival between low versus high expression. CONCLUSION: Although Yap, Akt, mTOR, and Erk protein are all expressed in Ewing's sarcoma by immunohistochemistry, only Akt expression is associated with worse prognosis. Larger studies are needed to verify these results and plan targeted therapy, particularly against Akt. PMID- 26366215 TI - Solanum Incanum Extract Downregulates Aldehyde Dehydrogenase 1-Mediated Stemness and Inhibits Tumor Formation in Ovarian Cancer Cells. AB - Solanum incanum extract (SR-T100), containing the active ingredient solamargine, can induce apoptosis via upregulation of tumor necrosis factor receptor expression and activation of the mitochondrial apoptosis pathway, and has therapeutic effects in patients with actinic keratosis. Here, we evaluate the novel molecular mechanisms underlying SR-T100-regulated stemness and chemoresistance. The concentration of SR-T100 that inhibited 50% cell viability (IC50) was lower in ovarian cancer cells than in nonmalignant cells. Furthermore, the SR-T100 IC50 in chemoresistant cells was similar to the IC50 in chemosensitive cells. Additionally, SR-T100 increased cisplatin and paclitaxel sensitivity in chemoresistant cells. SR-T100 downregulated the expression of stem cell markers, including aldehyde dehydrogenase 1 (ALDH1), Notch1, and FoxM1, and reduced sphere formation in ovarian cancer cells. Using microarray analyses, immunoblotting, luciferase activity, and chromatin immunoprecipitation (ChIP) assays, we showed that SR-T100 suppressed the expression of c/EBPbeta and COL11A1, and its promoter activity, in resistant cells, but not sensitive cells. SR-T100, paclitaxel, and cisplatin inhibited the growth of A2780CP70 cells in mouse xenografts, as compared to the vehicle control, and the combination of cisplatin and SR-T100 was more effective than either treatment alone. SR-T100 may represent a potential therapeutic adjunct to chemotherapy for ovarian cancer treatment. PMID- 26366216 TI - The Regulation of Matrix Metalloproteinase Expression and the Role of Discoidin Domain Receptor 1/2 Signalling in Zoledronate-treated PC3 Cells. AB - Discoidin Domain Receptors (DDR1/DDR2) are tyrosine kinase receptors which are activated by collagen. DDR signalling regulates cell migration, proliferation, apoptosis and matrix metalloproteinase (MMP) production. MMPs degrade extracellular matrix (ECM) and play essential role in tumor growth, invasion and metastasis. Nitrogen-containing bisphosphonates (N-BPs) which strongly inhibit osteoclastic activity are commonly used for osteoporosis treatment. They also have MMP inhibitory effect. In this study, we aimed to investigate the effects of zoledronate in PC3 cells and the possible role of DDR signalling and downstream pathways in these inhibitory effects. We studied messenger RNA (mRNA) and protein expressions of MMP-2,-9,-8, DDR1/DDR2 type I procollagen (TIP) and mRNA levels of PCA-1, MMP-13 and DDR-initiated signalling pathway players including K-Ras oncogene, ERK1, JNK1, p38, AKT-1 and BCLX in PC3 cells in the presence or absence of zoledronate (10-100 MUM) for 2-3 days. Zoledronate (100 MUM) down-regulated DDR1/ DDR2, TIP mRNAs but did not change MMP-13 (collagenase-3) mRNA. However, zoledronate up-regulated MMP-8 (collagenase-2) mRNA. Zoledronate also inhibited mRNA expressions of K-Ras, ERK1, AKT-1, BCLX and PCA-1; but did not change JNK1, p38 mRNA levels. Zoledronate (100 MUM) supressed DDR1/DDR2, TIP expressions; and gelatinase (MMP-2/MMP-9) expressions/activities. Conversely, zoledronate up regulated MMP-8 expression in PC3 cells. Zoledronate down-regulates MMP-2/-9 expressions in PC3 prostate cancer cells. DDR1/DDR2 signalling and DDR-initiated downstream Ras/Raf/ERK and PI3K/AKT pathways may at least partially responsible for MMP inhibitory effect of zoledronate. PMID- 26366217 TI - The Expression and Function of NUMB in Endometrial Cancer and the Interaction with HDM2 and P53. AB - BACKGROUND: Since more and more evidences support that NUMB orchestrates many cell physiological and pathological processes of diseases including cancer, based on our previous work, we studied deeply the function of NUMB in endometrial cancer (EC) and tried to understand the mechanism of NUMB's nucleus translocation which might be relative to the occurrence of EC and will contribute to find a new targeting therapeutic strategy for EC. METHODS: Immunohistochemistry was employed to test NUMB and HDM2 expression in endometrial cancer tissue from clinical patients. CCK-8 assay, cell cycle tested by Flow cytometer and PCNA determined by RT-PCR were employed to test the effects of NUMB on cell proliferation and apoptosis. In order to investigate the mechanism how NUMB, HDM2 and p53 interact in EC cell, western blot, Co-IP and immunofluorescent were used to observe the combination and location of NUMB, HDM2 and p53 as well as the interaction among them. RESULTS: Both NUMB and HDM2 expressed greater in endometrial cancer tissues than in normal endometrial tissues. Overexpression of NUMB induced apoptosis in Ishikawa cell while inhibition of NUMB increased cell proliferation. NUMB could combine HDM2 and p53, moreover the PTB domain of NUMB is the main site combining with p53. The effects of NUMB in cell was closely associated with p53. Not only NUMB regulated P53 expression level but also NUMB acts depending on P53, in turn p53 impacted the NUMB level as a feedback. Overexpression of NUMB could not bring itself into nuclear. Both siHDM2 and siP53 didn't bring NUMB into nucleus, However overexpression of HDM2 and p53 increased the NUMB level in nucleus, and the NUMB nuclear location induced by overexpression of HDM2 was stronger than that of p53 overexpression. CONCLUSIONS: Based on present data, we think NUMB acts as an anti-oncogene role and could regulate p53 level and function in endometrial cancer like in other cancers, meanwhile, the function of NUMB depend on P53. On the other hand, the location of NUMB could be regulated mainly by HDM2. So far we are not able to explain why endometrial cancer patients had high NUMB expression level since NUMB was regarded as a tumor suppressor, which is worthy studying further to explore underlying mechanism. PMID- 26366218 TI - A Muti-center, Randomized Phase II Study of Oxaliplatin and S-1 versus Capecitabine and Oxaliplatin in Patients with Metastatic Colorectal Cancer. AB - BACKGROUND: Capecitabine plus oxaliplatin (XELOX) is considered one of the primary chemotherapy regimens for patients with metastatic colorectal cancer (CRC). Oxaliplatin plus S-1 (OS) has also demonstrated significant efficacy in CRC. We performed this randomized phase II study to evaluate the efficacy and toxicity of XELOX versus OS as first-line chemotherapy in patients with metastatic CRC. METHODS: Patients were assigned randomly to receive either OS or XELOX chemotherapy. Oxaliplatin was administered intravenously to all patients at a dose of 130 mg/m(2) on day 1. Patients received either S-1 (40 mg/m(2)) or capecitabine (1,000 mg/m(2)), twice a day for 2 weeks, followed by a 1-week rest. RESULTS: Forty-two patients were assigned to the OS arm and 44 to the XELOX arm. The overall response rate was 33.3% (95% CI, 18.8-47.2) in the OS arm and 40.9% (95% CI, 25.5-54.4) in the XELOX arm (P = 0.230). The disease control rate was significantly higher in the OS arm than the XELOX arm [92.9% (95% CI, 83.7-100) versus 77.3% (95% CI, 64.5-89.4), P = 0.044]. With a median follow up of 17.9 months, the median progression-free survival was 6.1 months in the OS arm and 7.4 months in the XELOX arm, respectively (P = 0. 599). The median survival time was 18.7 months in the OS arm and 20.1 months in the XELOX arm (P = 0.340). The most common grade 3/4 hematologic toxicity was thrombocytopenia in both arms (19.0% for OS and 28.6% for XELOX). Grade 3/4 neutropenia was observed more frequently in the XELOX arm than the OS arm (16.7% vs. 2.4%, P = 0.026). CONCLUSION: Both OS and XELOX were effective and well tolerated in patients with metastatic CRC. Our results indicate that the combination of oxaliplatin and S-1 is a possible additional therapeutic strategy for such patients. PMID- 26366219 TI - Staurosporine Induced Apoptosis May Activate Cancer Stem-Like Cells (CD44(+)/CD24(-)) in MCF-7 by Upregulating Mucin1 and EpCAM. AB - Malignant tumors recur after chemotherapy. A small population of cancer stem-like cells within tumors is now generally considered the prime source of the recurrence. To better understand how cancer stem-like cells induce relapse after fractionated chemotherapy, we examined changes in the CD44(+)/CD24(-) cancer stem like cells population and behavior using the breast cancer cell line MCF-7. Our results show that apart from an increase in the CD44(+)/CD24(-) population, proliferation and clone formation, but not migration, were enhanced after recovery from apoptosis induced by two pulses of staurosporine (STS). The distribution of cells in the cell cycle differed between acutely induced apoptosis and fractionated chemotherapy. Sorted CD44(+)/CD24(-) stem-like cells from MCF-7 cells recovered from STS treatment possessed greater proliferation abilities. We also observed that mucin1 (MUC1) and Epithelial cell adhesion molecule (EpCAM) were up-regulated in abundance coincidently with proliferation and clone formation enhancement. Our findings suggest that fractionated chemotherapy induced apoptosis could stimulate cancer stem-like cell to behave with a stronger malignant property than cancer cells themselves and MUC1 and EpCAM are important factors involving in this process. By demonstrating changes in cancer stem cell during chemotherapy and identifying the crucial factors, we potentially can target them, to eradicate tumors and overcome cancer relapse. PMID- 26366221 TI - Value recognition. PMID- 26366222 TI - Plasmatic markers for early diagnostic and treatment decisions in ischemic stroke. AB - A neurologic deficit of sudden onset conforming to a vascular territory is a clear clinical indication that a patient suffers from an acute stroke. However, the imagistic diagnostic confirmation is not always readily available. We are now able to offer comprehensive medical support for the patient after an acute stroke and to make a prodigious rehabilitation program after the damage is done, but this is not offering the chance for improvement. An opportunity to better diagnose ischemic stroke seems to be available by using neuronal biomarkers. Extensive research is being conducted in this field and useful information is beginning to gather. This mini-review aims to highlight selected studies that appear to be of particular interest for the clinical neurologist. The most promising biomarkers (or rather panels of biomarkers) are presented with theirs clinical usefulness and limitations. PMID- 26366223 TI - Placental damages in preeclampsia - from ultrasound images to histopathological findings. AB - Preeclampsia is a unique pregnancy-related disease that affects 5-7% pregnancies worldwide. Placental architecture is modified in PE and eclampsia. Placental morphology and cellular arrangement are important for oxygen delivery from the mother to the fetus. Fetal growth and well-being after 20 weeks of gestation are dependent upon successful placental development. This, in turn, is achieved by an enhanced maternal blood supply to the placenta (normal uterine artery Doppler) and growth/ differentiation of the gas-exchanging placental villi. Conversely, pregnancy with severe placental insufficiency exhibits abnormalities both in uterine artery and in umbilical artery Doppler, and results in adverse perinatal outcome. The evaluation of placental functioning is possible nowadays through ultrasound examinations. Sonographic images associated with placental lesions include cystic areas, heterogeneous appearance of the placental mass, and thick or thin placentas. Sonographic evidence of destructive placental lesions is defined as the evolution of irregular cystic spaces with echogenic borders - the echogenic cystic lesions. Histological examinations of placenta may confirm these antepartum observations. Decidual vasculopathy and accelerated villous maturity are considered indicative of uteroplacental vascular insufficiency. Perivillous fibrin deposition and intervillous fibrin are considered indicative of intervillous coagulation. Detailed sonographic evaluation of the placenta and histopathological confirmation after birth are used to identify lesions associated with preeclampsia, intrauterine growth restriction and adverse short and long-term perinatal outcome, but the presence of cystic images in the placenta is not uniformly associated with adverse perinatal outcome. Combining Doppler studies with placental texture studies may lead to satisfactory results. PMID- 26366220 TI - Weaknesses and Pitfalls of Using Mice and Rats in Cancer Chemoprevention Studies. AB - Many studies, using different chemical agents, have shown excellent cancer prevention efficacy in mice and rats. However, equivalent tests of cancer prevention in humans require decades of intake of the agents while the rodents' short lifespans cannot give us information of the long-term safety. Therefore, animals with a much longer lifespan should be used to bridge the lifespan gap between the rodents and humans. There are many transgenic mouse models of carcinogenesis available, in which DNA promoters are used to activate transgenes. One promoter may activate the transgene in multiple cell types while different promoters are activated at different ages of the mice. These spatial and temporal aspects of transgenes are often neglected and may be pitfalls or weaknesses in chemoprevention studies. The variation in the copy number of the transgene may widen data variation and requires use of more animals. Models of chemically induced carcinogenesis do not have these transgene-related defects, but chemical carcinogens usually damage metabolic organs or tissues, thus affecting the metabolism of the chemopreventive agents. Moreover, many genetically edited and some chemically-induced carcinogenesis models produce tumors that exhibit cancerous histology but are not cancers because the tumor cells are still mortal, inducer-dependent, and unable to metastasize, and thus should be used with caution in chemoprevention studies. Lastly, since mice prefer an ambient temperature of 30-32 degrees C, it should be debated whether future mouse studies should be performed at this temperature, but not at 21-23 degrees C that cold stresses the animals. PMID- 26366224 TI - Tear lipocalin, lysozyme and lactoferrin concentrations in postmenopausal women. AB - RATIONALE: Among the most frequently encountered pathologies examined by the ophthalmologist is dry eye syndrome (DE), which can be discovered particularly in the elderly. The initial diagnosis of DE is of high importance, but also challenging. This is because the biochemical changes in the tear film often develop before any detectable signs. OBJECTIVE: In this study, the possible relationship between ocular symptomatology, tear volume and tear break-up time (TBUT) and lipocalin, lactoferrin and lysozyme concentrations in the tear film were explored in a group of symptomatic dry-eyed postmenopausal (PM) women compared to age-matched controls. PATIENTS AND METHODS: Sixty-six healthy PM females with ages of at least 50 years were grouped in two homogeneous lots (by age, post-menopause, co-morbidities) of 33 females each, one lot presenting mild or moderate dry eye syndrome (DE) and one asymptomatic non-dry eye (NDE), based on their feedback to the Ocular Surface Disease Index (OSDI) questionnaire and noninvasive TBUT and Schirmer test results. Tears were collected via capillary tubes and an eye wash method. Tear lysozyme, lactoferrin and lipocalin concentrations were determined via electrophoresis. RESULTS: OSDI responses revealed 3 mild DE, 30 moderate DE and 33 NDE. The OSDI total score and sub scores for the DE group were significantly greater than for the NDE group (p < 0.001). The mild and moderate DE group exhibited significantly shorter TBUTs compared to NDE (p < 0.001). No difference in tear lysozyme or lipocalin concentrations was found between DE and NDE groups, irrespective of the tear collection method, but a significant difference was found in lactoferrin concentration (p<0.001). No significant correlations were found between symptoms or signs of DE compared to either lipocalin, lysozyme or lactoferrin concentrations. DISCUSSION: In a PM population, lipocalin and lysozyme are invariable, irrespective of the presence and severity of DE symptoms. However, lactoferrin shows a significant decrease. This is a comprehensive study of lipocalin, lactoferrin and lysozyme in dry-eyed PM women and our results suggested that lactoferrin could be used as a biomarker of DE in postmenopausal women. ABBREVIATIONS: PM = postmenopausal; DE = dry eye disease; NDE = non-dry eye; ELISA = Enzyme-linked immunosorbent assay. PMID- 26366225 TI - Putative intestinal stem cells. AB - A heterogeneous set of intestinal stem cells markers has been described in intestinal glands but the ultrastructural identity of intestinal stem cells remains unknown. By using electron microscopy, this study demonstrated the presence of cells with stem morphology in the intestinal glands of mice of different ages. These putative intestinal stem cells have large, euchromatic, irregular shaped nucleus, large, visible nucleolus, few ER cisternae and mitochondria. Their morphology is distinct from the morphology of any other intestinal gland cell. Stem cells located at the base of intestinal glands undergo mitosis. This study enhances the hypothesis of a gland (crypt) base columnar cell that gives rise to all the intestinal lineages. PMID- 26366226 TI - Study regarding the survival of patients suffering a traumatic cardiac arrest. AB - Severe trauma is the most frequent cause of death in young people, in civilized countries with major social and vital costs. The speed of diagnostic decision making and the precocity of treatment approaches are both essential and depend on the specialists' colaboration. The present study aims to emphasize the actual situation of medical interventions in case of cardiorespiratory arrest due to trauma. 1387 patients who suffered a cardio respiratory arrest both traumatic and non-traumatic were included in order to point out the place of traumatic arrest. Resuscitation of such patients is considered useless and resource consumer by many trauma practitioners who are reporting survival rates of 0%-3.5%. As the determinant of lesions, trauma etiology was as it follows car accidents - 43%, high falls - 30%, suicidal attempts - 3%, domestic violence - 3%, other causes - 21%. Hypovolemia remains the major cause of cardiac arrest and death and that is why the efforts of emergency providers (trauma team) must be oriented towards "hidden death" in order to avoid it. This condition could be revealed and solved easier with minimal diagnostic and therapeutic maneuvers in the emergency department. PMID- 26366227 TI - Socio-economical factors that influence the perception of quality of life in patients with osteoporosis. AB - The appearance of osteoporosis in elders and the growth of the frequency which it is diagnosed with as we approach patients who are older and older, makes this health problem very important in the societies in which a high number of persons reach old age. These societies, usually belonging to economically advanced jurisdictions, are the first interested in the way health expenses can balance the benefits of the quality of life acquired in these groups of population. The evaluation of the quality of life has become a very important process, which still raises methodological problems to the researchers. The aim of this study was to analyze to what extent the factors involved in defining the quality of life by the patients modified according to the existence of osteoporosis as a defined but also as a perceived disease, as far as it is considered a serious or less serious affection by each patient. 210 female patients participated in the study. The statistical analysis was done by using SPSS 22.0 (IBM Corp. - U.S.A.). p < 0,05 was used as a limit for the statistical significance. Descriptive and analytical analyses were made by following Pearson correlation index in cases of normal distributions, the comparison between groups was made by using t-Student test, respectively chi square test in the cases which required its use. The current study highlights a direct relationship between the quality of life, as it is perceived by the patients, and the quality of the health status, which is more important than the relationship between the quality of life and the other objectives measured by WHOQOL scale. This study also shows that for the Romanian patient diagnosed with osteoporosis, who is enclosed in the age limits of this study, the health status represents the main driver of monitoring the quality of life. PMID- 26366229 TI - The 2015 Young Innovators of Cellular and Molecular Bioengineering. PMID- 26366228 TI - Strategies for efficient numerical implementation of hybrid multi-scale agent based models to describe biological systems. AB - Biologically related processes operate across multiple spatiotemporal scales. For computational modeling methodologies to mimic this biological complexity, individual scale models must be linked in ways that allow for dynamic exchange of information across scales. A powerful methodology is to combine a discrete modeling approach, agent-based models (ABMs), with continuum models to form hybrid models. Hybrid multi-scale ABMs have been used to simulate emergent responses of biological systems. Here, we review two aspects of hybrid multi scale ABMs: linking individual scale models and efficiently solving the resulting model. We discuss the computational choices associated with aspects of linking individual scale models while simultaneously maintaining model tractability. We demonstrate implementations of existing numerical methods in the context of hybrid multi-scale ABMs. Using an example model describing Mycobacterium tuberculosis infection, we show relative computational speeds of various combinations of numerical methods. Efficient linking and solution of hybrid multi scale ABMs is key to model portability, modularity, and their use in understanding biological phenomena at a systems level. PMID- 26366230 TI - Nanopatterned Human iPSC-based Model of a Dystrophin-Null Cardiomyopathic Phenotype. AB - Human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) offer unprecedented opportunities to study inherited heart conditions in vitro, but are phenotypically immature, limiting their ability to effectively model adult-onset diseases. Cardiomyopathy is becoming the leading cause of death in patients with Duchenne muscular dystrophy (DMD), but the pathogenesis of this disease phenotype is not fully understood. Therefore, we aimed to test whether biomimetic nanotopography could further stratify the disease phenotype of DMD hiPSC-CMs to create more translationally relevant cardiomyocytes for disease modeling applications. We found that anisotropic nanotopography was necessary to distinguish structural differences between normal and DMD hiPSC-CMs, as these differences were masked on conventional flat substrates. DMD hiPSC-CMs exhibited a diminished structural and functional response to the underlying nanotopography compared to normal cardiomyocytes at both the macroscopic and subcellular levels. This blunted response may be due to a lower level of actin cytoskeleton turnover as measured by fluorescence recovery after photobleaching. Taken together these data suggest that DMD hiPSC-CMs are less adaptable to changes in their extracellular environment, and highlight the utility of nanotopographic substrates for effectively stratifying normal and structural cardiac disease phenotypes in vitro. PMID- 26366231 TI - Design of a Novel 3D Printed Bioactive Nanocomposite Scaffold for Improved Osteochondral Regeneration. AB - Chronic and acute osteochondral defects as a result of osteoarthritis and trauma present a common and serious clinical problem due to the tissue's inherent complexity and poor regenerative capacity. In addition, cells within the osteochondral tissue are in intimate contact with a 3D nanostructured extracellular matrix composed of numerous bioactive organic and inorganic components. As an emerging manufacturing technique, 3D printing offers great precision and control over the microarchitecture, shape and composition of tissue scaffolds. Therefore, the objective of this study is to develop a biomimetic 3D printed nanocomposite scaffold with integrated differentiation cues for improved osteochondral tissue regeneration. Through the combination of novel nano-inks composed of organic and inorganic bioactive factors and advanced 3D printing, we have successfully fabricated a series of novel constructs which closely mimic the native 3D extracellular environment with hierarchical nanoroughness, microstructure and spatiotemporal bioactive cues. Our results illustrate several key characteristics of the 3D printed nanocomposite scaffold to include improved mechanical properties as well as excellent cytocompatibility for enhanced human bone marrow-derived mesenchymal stem cell adhesion, proliferation, and osteochondral differentiation in vitro. The present work further illustrates the effectiveness of the scaffolds developed here as a promising and highly tunable platform for osteochondral tissue regeneration. PMID- 26366232 TI - Nucleated red blood cells impact DNA methylation and expression analyses of cord blood hematopoietic cells. AB - BACKGROUND: Genome-wide DNA methylation (DNAm) studies have proven extremely useful to understand human hematopoiesis. Due to their active DNA content, nucleated red blood cells (nRBCs) contribute to epigenetic and transcriptomic studies derived from whole cord blood. Genomic studies of cord blood hematopoietic cells isolated by fluorescence-activated cell sorting (FACS) may be significantly altered by heterotopic interactions with nRBCs during conventional cell sorting. RESULTS: We report that cord blood T cells, and to a lesser extent monocytes and B cells, physically engage with nRBCs during FACS. These heterotopic interactions resulted in significant cross-contamination of genome wide epigenetic and transcriptomic data. Formal exclusion of erythroid lineage specific markers yielded DNAm profiles (measured by the Illumina 450K array) of cord blood CD4 and CD8 T lymphocytes, B lymphocytes, natural killer (NK) cells, granulocytes, monocytes, and nRBCs that were more consistent with expected hematopoietic lineage relationships. Additionally, we identified eight highly differentially methylated CpG sites in nRBCs (false detection rate <5 %, |Deltabeta| >0.50) that can be used to detect nRBC contamination of purified hematopoietic cells or to assess the impact of nRBCs on whole cord blood DNAm profiles. Several of these erythroid markers are located in or near genes involved in erythropoiesis (ZFPM1, HDAC4) or immune function (MAP3K14, IFIT1B), reinforcing a possible immune regulatory role for nRBCs in early life. CONCLUSIONS: Heterotopic interactions between erythroid cells and white blood cells can result in contaminated cell populations if not properly excluded during cell sorting. Cord blood nRBCs have a distinct DNAm profile that can significantly skew epigenetic studies. Our findings have major implications for the design and interpretation of genome-wide epigenetic and transcriptomic studies using human cord blood. PMID- 26366233 TI - Epidemiologic evidence for association between adverse environmental exposures in early life and epigenetic variation: a potential link to disease susceptibility? AB - A growing body of evidence suggests that the risk of development and progression of a variety of human chronic diseases depends on epigenetic modifications triggered by environmental cues during early life sensitive stages. Exposures to environmental factors such as adverse nutritional, psychological, and social conditions, as well as pollutants and substance abuse in early life, have been shown to be important determinants of epigenetic programming of chronic pathological conditions in human populations. Over the past years, it has become increasingly clear due to the epigenome-wide association studies (EWASs) that early life adverse environmental events may trigger widespread and persistent alterations in transcriptional profiling. Several candidate genes have been identified underlying these associations. In this context, DNA methylation is the most intensively studied epigenetic phenomenon. In this review, the clinical and epidemiological evidence for the role of epigenetic factors in mediating the link between early life experiences and long-term health outcomes are summarized. PMID- 26366234 TI - Epigenetic synergy between decitabine and platinum derivatives. AB - BACKGROUND: Aberrant epigenetic silencing of tumor suppressor genes has been recognized as a driving force in cancer. Epigenetic drugs such as the DNA methylation inhibitor decitabine reactivate genes and are effective in myeloid leukemia, but resistance often develops and efficacy in solid tumors is limited. To improve their clinical efficacy, we searched among approved anti-cancer drugs for an epigenetic synergistic combination with decitabine. RESULTS: We used the YB5 cell line, a clonal derivative of the SW48 colon cancer cell line that contains a single copy of a hypermethylated cytomegalovirus (CMV) promoter driving green fluorescent protein (GFP) to screen for drug-induced gene reactivation and synergy with decitabine. None of the 16 anti-cancer drugs tested had effects on their own. However, in combination with decitabine, platinum compounds showed striking synergy in activating GFP. This was dose dependent, observed both in concurrent and sequential combinations, and also seen with other alkylating agents. Clinically achievable concentrations of carboplatin at (25 MUM) and decitabine reactivated GFP in 28 % of the YB5 cells as compared to 15 % with decitabine alone. Epigenetic synergy was also seen at endogenously hypermethylated tumor suppressor genes such as MLH1 and PDLIM4. Genome-wide studies showed that reactivation of hypermethylated genes by the combination was significantly better than that induced by decitabine alone or carboplatin alone. Platinum compounds did not enhance decitabine-induced hypomethylation. Rather, we found significantly inhibited HP1alpha expression by carboplatin and the combination. This was accompanied by increased histone H3 lysine 4 (H3K4) trimethylation and histone H3 lysine 9 (H3K9) acetylation at reactivated genes (P < 0.0001) and reduced occupancy by methyl-binding proteins including MeCP2 and methyl-CpG-binding domain protein 2 (MBD2) (P < 0.0001). CONCLUSIONS: Our results suggest that the combination of decitabine with platinum analogs shows epigenetic synergy that might be exploited in the treatment of different cancers. PMID- 26366235 TI - Induction of active demethylation and 5hmC formation by 5-azacytidine is TET2 dependent and suggests new treatment strategies against hepatocellular carcinoma. AB - BACKGROUND: Global deregulation of DNA methylation is one of the crucial causes of hepato cellular carcinoma (HCC). It has been reported that the anti-cancer drug 5-azacytidine (5-AZA) mediates the activation of tumor suppressor genes through passive demethylation by inhibiting DNMT1. Recent evidence suggests that active demethylation which is mediated by ten-eleven translocation (TET) proteins may also be an important step to control global methylation. However, there exists a controversial discussion in which TET proteins are involved in the demethylation process in HCC. Therefore, we firstly wanted to identify which of the TETs are involved in demethylation and later to study whether or not 5-AZA could trigger the TET-dependent active demethylation process in HCC. HCC cell lines (Huh-7, HLE, HLF), primary human hepatocytes (hHeps), and tissues from both healthy (55 patients) and HCC patients (55 patients) were included in this study; mRNA levels of isocitrate dehydrogenase (IDH1, 2) and TETs (TET1-3) were studied via qPCR and confirmed by Western blot. The expression of 5hmC/5mC was determined by immunohistochemistry in human HCC tissues and the corresponding adjacent healthy liver. HCC cell lines were stimulated with 5-AZA (0-20 MUM) and viability (Resazurin conversion), toxicity (LDH release), proliferation (PCNA), and 5hmC/5mC distribution were assessed. In addition, knockdown experiments on TET proteins in HCC cell lines using short interference RNAs (siRNAs), in the presence and absence of 5-AZA, were performed. RESULTS: Our data applying qPCR, immunofluorescence, and Western blotting clearly show that TET2 and TET3 but not TET1 were significantly decreased in HCC tissue and different HCC cell lines compared to non-tumor liver tissues and hHeps. In addition, we show here for the first time applying knockdown experiments that 5-AZA is able to trigger an active TET2-dependent demethylation process with concomitant significant changes in 5hmC/5mC in HCC cell lines and hHeps. CONCLUSIONS: Our data clearly show that the expression and activity of TET2 and TET3 proteins but not TET1 are impaired in hepatocellular carcinoma leading to the reduction of 5hmC in HCCs. Furthermore, this study identified a novel function of 5-azacytidine in promoting a TET mediated generation of 5hmC suggesting that the availability of 5-AZA in cancer cells will have various effects on different epigenetic targets. These findings may open new therapeutic strategies for epigenetic drugs to treat HCC. PMID- 26366236 TI - Prostate-Specific Antigen (PSA)-Based Population Screening for Prostate Cancer: An Evidence-Based Analysis. AB - BACKGROUND: Prostate cancer (PC) is the most commonly diagnosed non-cutaneous cancer in men and their second or third leading cause of cancer death. Prostate specific antigen (PSA) testing for PC has been in common practice for more than 20 years. OBJECTIVES: A systematic review of the scientific literature was conducted to determine the effectiveness of PSA-based population screening programs for PC to inform policy decisions in a publicly funded health care system. DATA SOURCES: A systematic review of bibliographic databases was performed for systematic reviews or randomized controlled trials (RCT) of PSA based population screening programs for PC. REVIEW METHODS: A broad search strategy was employed to identify studies reporting on key outcomes of PC mortality and all-cause mortality. RESULTS: The search identified 5 systematic reviews and 6 RCTs. None of the systematic reviews found a statistically significant reduction in relative risk (RR) of PC mortality or overall mortality with PSA-based screening. PC mortality reductions were found to vary by country, by screening program, and by age of men at study entry. The European Randomized Study of Screening for Prostate Cancer found a statistically significant reduction in RR in PC mortality at 11-year follow-up (0.79; 95% CI, 0.67-0.92), although the absolute risk reduction was small (1.0/10,000 person-years). However, the primary treatment for PCs differed significantly between countries and between trial arms. The American Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) found a statistically non-significant increase in RR for PC mortality with 13-year follow-up (1.09; 95% CI, 0.87-1.36). The degree of opportunistic screening in the control arm of the PLCO trial, however, was high. None of the RCTs found a reduction in all-cause mortality and all found a statistically significant increase in the detection of mainly low-risk, organ confined PCs in the screening arm. CONCLUSIONS: There was no evidence of a PC mortality reduction in the American PLCO trial, which investigated a screening program in a setting where opportunistic screening was already common practice. Given that opportunistic PSA screening practices in Canada are similar, it is unlikely that the introduction of a formal PSA screening program would reduce PC mortality. PMID- 26366237 TI - Prostate-Specific Antigen (PSA)-Based Population Screening for Prostate Cancer: An Economic Analysis. AB - BACKGROUND: The prostate-specific antigen (PSA) blood test has become widely used in Canada to test for prostate cancer (PC), the most common cancer among Canadian men. Data suggest that population-based PSA screening may not improve overall survival. OBJECTIVES: This analysis aimed to review existing economic evaluations of population-based PSA screening, determine current spending on opportunistic PSA screening in Ontario, and estimate the cost of introducing a population-based PSA screening program in the province. METHODS: A systematic literature search was performed to identify economic evaluations of population-based PSA screening strategies published from 1998 to 2013. Studies were assessed for their methodological quality and applicability to the Ontario setting. An original cost analysis was also performed, using data from Ontario administrative sources and from the published literature. One-year costs were estimated for 4 strategies: no screening, current (opportunistic) screening of men aged 40 years and older, current (opportunistic) screening of men aged 50 to 74 years, and population based screening of men aged 50 to 74 years. The analysis was conducted from the payer perspective. RESULTS: The literature review demonstrated that, overall, population-based PSA screening is costly and cost-ineffective but may be cost effective in specific populations. Only 1 Canadian study, published 15 years ago, was identified. Approximately $119.2 million is being spent annually on PSA screening of men aged 40 years and older in Ontario, including close to $22 million to screen men younger than 50 and older than 74 years of age (i.e., outside the target age range for a population-based program). A population-based screening program in Ontario would cost approximately $149.4 million in the first year. LIMITATIONS: Estimates were based on the synthesis of data from a variety of sources, requiring several assumptions and causing uncertainty in the results. For example, where Ontario-specific data were unavailable, data from the United States were used. CONCLUSIONS: PSA screening is associated with significant costs to the health care system when the cost of the PSA test itself is considered in addition to the costs of diagnosis, staging, and treatment of screen-detected PCs. PMID- 26366238 TI - Positional Magnetic Resonance Imaging for People With Ehlers-Danlos Syndrome or Suspected Craniovertebral or Cervical Spine Abnormalities: An Evidence-Based Analysis. AB - BACKGROUND: Ehlers-Danlos syndrome (EDS) is an inherited disorder affecting the connective tissue. EDS can manifest with symptoms attributable to the spine or craniovertebral junction (CVJ). In addition to EDS, numerous congenital, developmental, or acquired disorders can increase ligamentous laxity in the CVJ and cervical spine. Resulting abnormalities can lead to morbidity and serious neurologic complications. Appropriate imaging and diagnosis is needed to determine patient management and need for complex surgery. Some spinal abnormalities cause symptoms or are more pronounced while patients sit, stand, or perform specific movements. Positional magnetic resonance imaging (pMRI) allows imaging of the spine or CVJ with patients in upright, weight-bearing positions and can be combined with dynamic maneuvers, such as flexion, extension, or rotation. Imaging in these positions could allow diagnosticians to better detect spinal or CVJ abnormalities than recumbent MRI or even a combination of other available imaging modalities might allow. OBJECTIVES: To determine the diagnostic impact and clinical utility of pMRI for the assessment of (a) craniovertebral or spinal abnormalities among people with EDS and (b) major craniovertebral or cervical spine abnormalities among symptomatic people. DATA SOURCES: A literature search was performed using Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non Indexed Citations, Ovid Embase, and EBM Reviews, for studies published from January 1, 1998, to September 28, 2014. REVIEW METHODS: Studies comparing pMRI to recumbent MRI or other available imaging modalities for diagnosis and management of spinal or CVJ abnormalities were reviewed. All studies of spinal or CVJ imaging in people with EDS were included as well as studies among people with suspected major CVJ or cervical spine abnormalities (cervical or craniovertebral spine instability, basilar invagination, cranial settling, cervical stenosis, spinal cord compression, Chiari malformation). RESULTS: No studies were identified that met the inclusion criteria. CONCLUSIONS: We did not identify any evidence that assessed the diagnostic impact or clinical utility of pMRI for (a) craniovertebral or spinal abnormalities among people with EDS or (b) major craniovertebral or cervical spine abnormalities among symptomatic people relative to currently available diagnostic modalities. PMID- 26366239 TI - Colon Capsule Endoscopy for the Detection of Colorectal Polyps: An Evidence-Based Analysis. AB - BACKGROUND: Colorectal cancer, a leading cause of mortality and morbidity in Ontario, can be prevented through early diagnosis and removal of precancerous polyps. Colon capsule endoscopy is a relatively new, minimally invasive test for detecting colorectal polyps. OBJECTIVE: The objectives of this analysis were to evaluate the diagnostic accuracy and safety of colon capsule endoscopy for the detection of colorectal polyps among adult patients with signs or symptoms of colorectal cancer or with increased risk of colorectal cancer, and to compare colon capsule endoscopy with alternative procedures. REVIEW METHODS: A literature search was performed using Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non Indexed Citations, Ovid EMBASE, the Wiley Cochrane Library, and the Centre for Reviews and Dissemination database, for studies published between 2006 and 2014. Data on diagnostic accuracy and safety were abstracted from included studies. Quality of evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation (GRADE). RESULTS: The search yielded 2,189 citations. Five studies, all of which evaluated PillCam COLON 2 (PCC2), met the inclusion criteria. The per-patient sensitivity and specificity for detecting colorectal polyps were meta-analyzed. Colon capsule endoscopy, using PCC2, had a pooled sensitivity and specificity of 87% (95% confidence interval [CI] 77%-93%) and 76% (95% CI 60%-87%), respectively, for the detection of a colorectal polyp at least 6 mm in size (GRADE: very low). PCC2 had a pooled sensitivity and specificity of 89% (95% CI 77%-95%) and 91% (95% CI 86%-95%), respectively, for the detection of a colorectal polyp at least 10 mm in size (GRADE: low). One study directly compared PCC2 with computed tomographic (CT) colonography and found no statistically significant difference in accuracy (GRADE: low). Few adverse events were reported with PCC2; 3.9% of patients (95% CI 2.4%-6.5%) experienced adverse effects related to bowel preparation. Capsule retention was the most serious adverse event and occurred in 0.8% of patients (95% CI 0.2%-2.4%) (GRADE: very low). CONCLUSIONS: In adult patients with signs, symptoms, or increased risk of colorectal cancer, there is low-quality evidence that colon capsule endoscopy using the PCC2 device has good sensitivity and specificity for detecting colorectal polyps. Low-quality evidence does not show a difference in accuracy between colon capsule endoscopy and CT colonography. There is very low-quality evidence that PCC2 has a good safety profile with few adverse events; capsule retention is the most serious complication. PMID- 26366240 TI - Colon Capsule Endoscopy for the Detection of Colorectal Polyps: An Economic Analysis. AB - BACKGROUND: Colorectal cancer is a leading cause of mortality and morbidity in Ontario. Most cases of colorectal cancer are preventable through early diagnosis and the removal of precancerous polyps. Colon capsule endoscopy is a non-invasive test for detecting colorectal polyps. OBJECTIVES: The objectives of this analysis were to evaluate the cost-effectiveness and the impact on the Ontario health budget of implementing colon capsule endoscopy for detecting advanced colorectal polyps among adult patients who have been referred for computed tomographic (CT) colonography. METHODS: We performed an original cost-effectiveness analysis to assess the additional cost of CT colonography and colon capsule endoscopy resulting from misdiagnoses. We generated diagnostic accuracy data from a clinical evidence-based analysis (reported separately), and we developed a deterministic Markov model to estimate the additional long-term costs and life years lost due to false-negative results. We then also performed a budget impact analysis using data from Ontario administrative sources. One-year costs were estimated for CT colonography and colon capsule endoscopy (replacing all CT colonography procedures, and replacing only those CT colonography procedures in patients with an incomplete colonoscopy within the previous year). We conducted this analysis from the payer perspective. RESULTS: Using the point estimates of diagnostic accuracy from the head-to-head study between colon capsule endoscopy and CT colonography, we found the additional cost of false-positive results for colon capsule endoscopy to be $0.41 per patient, while additional false-negatives for the CT colonography arm generated an added cost of $116 per patient, with 0.0096 life-years lost per patient due to cancer. This results in an additional cost of $26,750 per life-year gained for colon capsule endoscopy compared with CT colonography. The total 1-year cost to replace all CT colonography procedures with colon capsule endoscopy in Ontario is about $2.72 million; replacing only those CT colonography procedures in patients with an incomplete colonoscopy in the previous year would cost about $740,600 in the first year. LIMITATIONS: The difference in accuracy between colon capsule endoscopy and CT colonography was not statistically significant for the detection of advanced adenomas (>= 10 mm in diameter), according to the head-to-head clinical study from which the diagnostic accuracy was taken. This leads to uncertainty in the economic analysis, with results highly sensitive to changes in diagnostic accuracy. CONCLUSIONS: The cost effectiveness of colon capsule endoscopy for use in patients referred for CT colonography is $26,750 per life-year, assuming an increased sensitivity of colon capsule endoscopy. Replacement of CT colonography with colon capsule endoscopy is associated with moderate costs to the health care system. PMID- 26366241 TI - Effect of Increased Intensity of Physiotherapy on Patient Outcomes After Stroke: An Economic Literature Review and Cost-Effectiveness Analysis. AB - BACKGROUND: Functional improvements have been seen in stroke patients who have received an increased intensity of physiotherapy. This requires additional costs in the form of increased physiotherapist time. OBJECTIVES: The objective of this economic analysis is to determine the cost-effectiveness of increasing the intensity of physiotherapy (duration and/or frequency) during inpatient rehabilitation after stroke, from the perspective of the Ontario Ministry of Health and Long-term Care. DATA SOURCES: The inputs for our economic evaluation were extracted from articles published in peer-reviewed journals and from reports from government sources or the Canadian Stroke Network. Where published data were not available, we sought expert opinion and used inputs based on the experts' estimates. REVIEW METHODS: The primary outcome we considered was cost per quality adjusted life-year (QALY). We also evaluated functional strength training because of its similarities to physiotherapy. We used a 2-state Markov model to evaluate the cost-effectiveness of functional strength training and increased physiotherapy intensity for stroke inpatient rehabilitation. The model had a lifetime timeframe with a 5% annual discount rate. We then used sensitivity analyses to evaluate uncertainty in the model inputs. RESULTS: We found that functional strength training and higher-intensity physiotherapy resulted in lower costs and improved outcomes over a lifetime. However, our sensitivity analyses revealed high levels of uncertainty in the model inputs, and therefore in the results. LIMITATIONS: There is a high level of uncertainty in this analysis due to the uncertainty in model inputs, with some of the major inputs based on expert panel consensus or expert opinion. In addition, the utility outcomes were based on a clinical study conducted in the United Kingdom (i.e., 1 study only, and not in an Ontario or Canadian setting). CONCLUSIONS: Functional strength training and higher-intensity physiotherapy may result in lower costs and improved health outcomes. However, these results should be interpreted with caution. PMID- 26366242 TI - Pulmonary Rehabilitation in Ontario: A Cross-Sectional Survey. AB - BACKGROUND: Pulmonary rehabilitation (PR) is a comprehensive intervention of exercise training, education, and behaviour change to improve the physical and psychological condition of people with chronic respiratory disorders, such as chronic obstructive pulmonary disease (COPD) and to promote long-term adherence to health-enhancing behaviours. Although PR is considered the standard of care for patients with COPD who remain symptomatic despite bronchodilator therapies, current evidence suggests that only 1.15% of COPD patients across Canada have access to PR facilities for care. OBJECTIVES: The objectives of this study were to identify the number of health care facilities across Ontario providing PR services for patients with COPD, describe the scope of those services, and determine the province's current capacity to provide PR services relative to need, for the province as a whole and by local health integration network (LHIN). METHODS: The Pulmonary Rehabilitation Programs in Ontario (PRO) Survey was a province-wide, descriptive, cross-sectional survey of health care facilities (hospitals, family health teams, and community health centres). It was distributed to 409 facilities to collect information on various aspects of PR services in the province. RESULTS: Between April 2013 and February 2014, 187 facilities responded to the survey (46% response rate). Most responding centres (144) did not offer PR services, and only 43 were full PR sites providing a comprehensive program. Hospital-based programs made up the majority of sites offering full PR services (67%), followed by programs based at family health teams (19%) and community health centres (14%). More than 90% of PR programs are outpatient-based. The average wait time for outpatient PR was 6.9 weeks, and 58% of programs provide services 5 days per week. More than 80% of patients attending PR complete the full program. Across all program types, the total estimated provincial capacity for PR outpatient care is 4,524 patients per year, or 0.66% to 1.78% of patients with COPD, depending on the estimated prevalence of disease. LIMITATIONS: These results are representative of 12 of the 14 LHINs in Ontario due to low response rates in facilities in 2 LHINs. CONCLUSIONS: Although some increase in capacity has occurred since a similar survey in 2005, PR resources in Ontario are insufficient to support the delivery of care to people with COPD in accordance with clinical practice guideline recommendations. PMID- 26366243 TI - Caesarean Delivery Rate Review: An Evidence-Based Analysis. AB - BACKGROUND: In 2007, caesarean deliveries comprised 28% of all hospital deliveries in Ontario. Provincial caesarean delivery rates increased with maternal age and varied by Local Health Integration Network. However, the accepted rate of caesarean delivery in a low-risk maternal population remains unclear. OBJECTIVES: To review the literature to assess factors that affect the likelihood of experiencing a caesarean delivery, and to examine Ontario caesarean delivery rates to determine whether there is rate variation across the province. DATA SOURCES: Data sources included publications from OVID MEDLINE, OVID MEDLINE In-Process and Other Non-Indexed Citations, OVID Embase, EBSCO Cumulative Index to Nursing & Allied Health Literature (CINAHL), and EBM Reviews, as well as data from the Canadian Institute for Health Information Discharge Abstracts Database and the Better Outcomes and Registry Network. REVIEW METHODS: A mixed-methods approach was used, which included a systematic review of the literature to delineate factors associated with the likelihood of caesarean delivery and an analysis of administrative and clinical data on hospital deliveries in Ontario to determine provincial caesarean delivery rates, variation in rates, and reasons for variation. RESULTS: Fourteen systematic reviews assessed 14 factors affecting the likelihood of caesarean delivery; 7 factors were associated with an increased likelihood of caesarean delivery, and 2 factors were associated with a decreased likelihood. Five factors had no influence. One factor provided moderate-quality evidence supporting elective induction policies in low-risk women. The overall Ontario caesarean delivery rate in a very-low-risk population was 17%, but varied significantly across Ontario hospitals. LIMITATIONS: The literature review included a 5-year period and used only systematic reviews. The determination of Robson class for women is based on care received in hospital only, and the low risk population may have included data from women with obstetrical conditions that warranted a caesarean delivery. CONCLUSIONS: There is moderate-quality evidence that-compared with expectant management-an induction policy is associated with a decrease in caesarean delivery rates in low-risk women. There is significant caesarean delivery rate variation among Ontario hospitals. PMID- 26366244 TI - Use of Tumescence for Outpatient Abdominoplasty and Other Concurrent Body Contouring Procedures: A Review of 65 Consecutive Patients. AB - INTRODUCTION: Abdominoplasty is being increasingly performed as an outpatient procedure. The role of tumescent technique in decreasing postoperative pain and hospital stay has not been extensively studied. METHODS: We reviewed 65 consecutive patients who underwent tumescent abdominoplasty over 20 months by a single surgeon. All the patients were followed up for at least 1 year. The outcomes were evaluated in terms of systemic complications such as deep vein thrombosis and pulmonary embolism and local complications such as seroma, wound infection, and skin necrosis. RESULTS: Of the 65 patient records analyzed, 61 were of females and 4 of males. Average age for the patient population was 45.2 years. Mean follow-up was at least 1 year for all the patients. Ninety-five percent of patients could be discharged the same day with tumescent abdominoplasty, whereas 71% of the patients who underwent concurrent procedures with abdominoplasty were also able to go home the same day. All the patients reported excellent postoperative pain control. There was no report of deep vein thrombosis or pulmonary embolism in any of these patients. Wound complications occurred in 14 patients (21.6%), of which 12 patients had seroma (18.5%) and 2 had wound infection (3.1%). The seromas were treated with repeated aspirations or Jackson-Pratt drain placement, whereas the wound infections resolved with outpatient antibiotics. CONCLUSIONS: The safety and efficiency of outpatient abdominoplasty can be further facilitated by utilizing tumescence. Tumescence helps the patients be discharged sooner, usually the same day, mobilize sooner, and rely less on oral narcotics at home. PMID- 26366245 TI - Breeding for Bio-ethanol Production in Lolium perenne L.: Association of Allelic Variation with High Water-Soluble Carbohydrate Content. AB - Increasing the extractable sugar yield from perennial crops is one strategy to generate renewable fuels such as bio-ethanol. Lolium perenne L. (perennial ryegrass) can contain significant (>30% dry matter) water-soluble sugars in the form of polymeric fructan which is readily extracted, broken down and fermented to bio-ethanol. A population of L. perenne generated from four parents which differed in water-soluble carbohydrate (WSC) content was subjected to multiple rounds of selection and recombination on the basis of early spring WSC content to produce a high WSC, and a low WSC population. A control population was generated by selecting the same number of plants at random. The alleles present at six candidate gene loci were analysed before and after selection and correlated to WSC content. Significant differences in the allele frequency of L. perenne soluble-acid invertase1:4 were observed between the three populations with one haplotype significantly associated with the high WSC C2S+ population (after three rounds of selection and two rounds of recombination). Moreover, WSC content was also associated with biomass accumulation. Thus, in addition to a 2.84-fold increase in WSC yield, the C2S+ population also had 1.48-fold more biomass per plant, resulting in 3.9-fold higher WSC yield per plant than the control population. PMID- 26366246 TI - Effects on Lignin Structure of Coumarate 3-Hydroxylase Downregulation in Poplar. AB - The lignin structural ramifications of coumarate 3-hydroxylase (C3H) downregulation have not been addressed in hardwoods. Such information is required to accompany an assessment of the digestibility and bioenergy performance characteristics of poplar, in particular. Structurally rich 2D NMR methods were applied to the entire lignin fraction to delineate lignin p hydroxyphenyl:guaiacyl:syringyl (H:G:S) levels and linkage distribution changes (and to compare with traditional degradative analyses). C3H downregulation reduced lignin levels by half and markedly increased the proportion of H units relative to the normally dominant G and S units. Relative stem H unit levels were up by ~ 100-fold to ~ 31 %, almost totally at the expense of G units; differences in the lignin interunit linkage distributions were more subtle. The H level in the most drastically C3H-downregulated transgenic poplar falls well beyond the H:G:S compositional bounds of normal angiosperms. The response observed here, in poplar, differs markedly from that reported for alfalfa where the S:G ratio remained almost constant even at substantial H levels, highlighting the often differing responses among plant species. PMID- 26366247 TI - Gesture as a window onto communicative abilities: Implications for diagnosis and intervention. AB - Speakers around the globe gesture when they talk, and young children are no exception. In fact, children's first foray into communication tends to be through their hands rather than their mouths. There is now good evidence that children typically express ideas in gesture before they express the same ideas in speech. Moreover, the age at which these ideas are expressed in gesture predicts the age at which the same ideas are first expressed in speech. Gesture thus not only precedes, but also predicts, the onset of linguistic milestones. These facts set the stage for using gesture in two ways in children who are at risk for language delay. First, gesture can be used to identify individuals who are not producing gesture in a timely fashion, and can thus serve as a diagnostic tool for pinpointing subsequent difficulties with spoken language. Second, gesture can facilitate learning, including word learning, and can thus serve as a tool for intervention, one that can be implemented even before a delay in spoken language is detected. PMID- 26366248 TI - Disentangling Wording and Substantive Factors in the Spiritual Well-Being Scale. AB - We evaluated the extent to which the Spiritual Well-Being Scale (SWBS) may help to meet the need for multidimensional, psychometrically sophisticated measures of spiritual and religious traits. Although the various forms of validity of the scale have, for the most part, been supported by psychometric studies, conflicting evidence surrounding its dimensionality has called into question its structural validity. Specifically, numerous authors have suggested that a more appropriate factor structure for the SWBS includes further substantive factors in addition to the 2 factors that the scale was originally intended to measure. In the current study, we attempted to resolve these debates using a combination of exploratory and confirmatory factor analysis based investigations in the Lothian Birth Cohort, 1921 study. Our analyses suggested that the additional factors suggested in previous studies may not have reflected substantive constructs; but rather, common variance due to methodological factors. PMID- 26366249 TI - Trajectories of PTSD and Substance Use Disorders in a Longitudinal Study of Personality Disorders. AB - This study investigated the co-occurrence of posttraumatic stress disorder (PTSD) and substance use disorders (SUDs) in a sample (N = 668) recruited for personality disorders and followed longitudinally as part of the Collaborative Longitudinal Personality Disorders Study. The study both examined rates of co occurring disorders at baseline and temporal relationships between PTSD and substance use disorders over 4 years. Subjects with a lifetime history of PTSD at baseline had significantly higher rates of SUDs (both alcohol and drug) than subjects without PTSD. Latent class growth analysis, a relatively novel approach used to analyze trajectories and identify homogeneous subgroups of participant on the basis of probabilities of PTSD and SUD over time, identified 6 classes, which were compared with respect to a set of functioning and personality variables. The most consistent differences were observed between the group that displayed low probabilities of both SUD and PTSD and the group that displayed high probabilities of both. PMID- 26366250 TI - COMBINED DELAY AND GRAPH EMBEDDING OF EPILEPTIC DISCHARGES IN EEG REVEALS COMPLEX AND RECURRENT NONLINEAR DYNAMICS. AB - The dynamical structure of the brain's electrical signals contains valuable information about its physiology. Here we combine techniques for nonlinear dynamical analysis and manifold identification to reveal complex and recurrent dynamics in interictal epileptiform discharges (IEDs). Our results suggest that recurrent IEDs exhibit some consistent dynamics, which may only last briefly, and so individual IED dynamics may need to be considered in order to understand their genesis. This could potentially serve to constrain the dynamics of the inverse source localization problem. PMID- 26366251 TI - Closed Testing in Pharmaceutical Research: Historical and Recent Developments. AB - In pharmaceutical research, making multiple statistical inferences is standard practice. Unless adjustments are made for multiple testing, the probability of making erroneous determinations of significance increases with the number of inferences. Closed testing is a flexible and easily explained approach to controlling the overall error rate that has seen wide use in pharmaceutical research, particularly in clinical trials settings. In this article, we first give a general review of the uses of multiple testing in pharmaceutical research, with particular emphasis on the benefits and pitfalls of closed testing procedures. We then provide a more technical examination of a class of closed tests that use additive-combination-based and minimum-based p-value statistics, both of which are commonly used in pharmaceutical research. We show that, while the additive combination tests are generally far superior to minimum p-value tests for composite hypotheses, the reverse is true for multiple comparisons using closure-based testing. The loss of power of additive combination tests is explained in terms worst-case "hurdles" that must be cleared before significance can be determined via closed testing. We prove mathematically that this problem can result in the power of a closure-based minimum p-value test approaching 1, while the power of an closure-based additive combination test approaches 0. Finally, implications of these results to pharmaceutical researchers are given. PMID- 26366252 TI - Radiation dose-fractionation effects in spinal cord: comparison of animal and human data. AB - PURPOSE: Recognizing spinal cord dose limits in various fractionations is essential to ensure adequate dose for tumor control while minimizing the chance of radiation-induced myelopathy (RIM). This study aimed to determine the alpha/beta ratio of the spinal cord and the cord dose limit in terms of BED50, the biological equivalent dose (BED) that induces 50 % chance of RIM, by fitting data collected from published animal and patient studies. METHODS: RIM data from five rat studies; three large animal studies on monkeys, dogs, and pigs; and 18 patient studies were included for the investigation. The alpha/beta ratios were derived, respectively, for rat (group A), large animal (group B), patient (group C), and combined data (group D). RESULTS: The alpha/beta ratio (and its 95 % confidental interval) was 4.1 (3.2, 5.0) or 3.6 (2.6, 4.6) Gy for group A, depending on fitting algorithms. It was 3.9 (3.0, 4.8), 3.7 (2.2, 8.2) and 3.9 (3.0, 4.9) for groups B, C, and D, respectively. BED50 was 111 Gy for the combined data. It corresponds to a D50 of 73.4 Gy in 2 Gy/FX, or 19.0 Gy in single fraction. BED5, which is the BED to induce 5 % of RIM, was calculated to be 83.9 Gy. It corresponds to D5 of 55.4 Gy in 2 Gy/FX, or 16.2 Gy in single fraction. CONCLUSION: The study showed that all four groups had similar alpha/beta ratios close to 3.9 Gy, suggesting that the spinal cord has a similar fractionation effect for different species, including human beings. PMID- 26366254 TI - Non-Communicable Diseases: Shining a Light on Cardiovascular Disease, Oman's Biggest Killer. PMID- 26366253 TI - Metabolic response assessment with 18F-FDG PET/CT: inter-method comparison and prognostic significance for patients with non-small cell lung cancer. AB - OBJECTIVE: This study aimed to (1) compare the agreement of two evaluation methods of metabolic response in patients with non-small cell lung cancer (NSCLC) and determine their prognostic value and (2) explore an optimal cutoff of metabolic reduction to distinguish a more favorable subset of responders. METHODS: This is a secondary analysis of prospective studies. Enrolled patients underwent 18F-PET/CT within 2 weeks before, during, and months after radiotherapy (post-RT). Metabolic response was assessed using both Peter MacCallum (PM) method of qualitative visual assessment and University of Michigan (UM) method of semiquantitative measurement. The agreement between two methods determined response, and their prediction of outcome was analyzed. RESULTS: Forty-four patients with median follow-up of 25.2 months were analyzed. A moderate agreement was observed between PM- and UM-based response assessment (Kappa coefficient = 0.434), unveiling a significant difference in CMR rate (p = 0.001). Categorical responses derived from either method were significantly predictive of overall survival (OS) and progression-free survival (PFS) (p < 0.0001). Numerical percentage decrease of FDG uptake also showed significant correlations with survival, presenting a hazard ratio of 0.97 for both OS and PFS. A 75 % of SUV decrease was found to be the optimal cutoff to predict OS and 2-year progression. CONCLUSIONS: There was a modest discrepancy in metabolic response rates between PM and UM criteria, though both could offer predictive classification for survival. The percentage decrease provides an ordinal value that correlates with prolonged survival, recommending 75 % as the optimal threshold at identifying better responders. PMID- 26366256 TI - Simvastatin Use in Patients with Type 2 Diabetes Mellitus: The Effects on Oxidative Stress. AB - OBJECTIVES: Studies have shown that people with type 2 diabetes mellitus (T2DM) may develop atherosclerosis due to the disturbance in oxidative control and progressive dyslipidemia. Our study aimed to highlight the benefits of simvastatin treatment in improving serum lipids and reducing oxidative damage in patients with T2DM. METHODS: Our randomized control trial included 56 patients with T2DM and dyslipidemia. The participants were on glibenclamide (5mg/day) during the period of the study. The patients were divided into two study groups (groups 1 and 2). Group 1 was the control group and consisted of 31 patients. Group 2 consisted of 25 participants, who were given simvastatin 20mg tablet once daily for 12 weeks. The control group did not receive simvastatin. Both groups were followed-up for measurement of blood pressure, pulse rate, serum lipids, and parameters of oxidative stress. RESULTS: The simvastatin treated group showed a significant improvement with reduced erythrocyte glutathione compared to the control group (p<0.001). This was also associated with a significant reduction in erythrocyte malondialdehyde in the simvastatin treated group compared to the control group (p<0.001). Serum lipids reflected a similar improvement in the levels of erythrocyte malondialdehyde. CONCLUSION: Our study highlights the beneficial role of simvastatin in improving the degree of oxidative stress in patients with T2DM through its effects on serum lipids and lipid peroxidation. PMID- 26366255 TI - Herbal Medicines Use During Pregnancy: A Review from the Middle East. AB - The prevalence of the herbal medicines use is on the rise across the world, especially amongst pregnant women. The scenario in the Middle Eastern region was reviewed to explore the prevalence, usage pattern, motivation, and attitude towards use of herbal medicine by pregnant women. Literature published up to December 2012 showed the prevalence of herbal medicine use varied between 22.3 82.3%, implying a rising trend in the utilization of herbal medicine during pregnancy. The most common herbs used were peppermint, ginger, thyme, chamomile, sage, aniseed, fenugreek, and green tea. The most common reasons for use included the treatment of gastrointestinal disorders and cold and flu symptoms. The majority of women used these products during their first trimester, and did not reveal this information to their physician. Most women were advised by family and friends to use herbal medicines and believed they were more effective and had fewer side effects than modern medicine especially during pregnancy. In conclusion, the use of herbal medicine is prevalent among pregnant women in the Middle Eastern region and healthcare providers need to seek information pertaining to their use. PMID- 26366257 TI - The Effects of Low Birth Weight on School Performance and Behavioral Outcomes of Elementary School Children in Oman. AB - OBJECTIVES: Our study aimed to examine the effects of low birth weight (LBW) on the school performance and behavior of elementary school children in Oman. . METHODS: Data were gathered through a cross-sectional survey of nine elementary schools from the Muscat and A'Dhahirah regions. The study utilized a unique database created by linking information from the children's health cards and current academic and behavioral performance records. Information on children's performance in various areas such as language, mathematics, science, information technology, sports, and behavior were obtained from the school registers. Birth weight (BW) and selected sociodemographic data were obtained from the copy of their health cards kept by each school. A total of 542 elementary school children aged 7-11 years, who had completed grades 2-4, were surveyed. . RESULTS: Data from the school register revealed a very high rate (17.7%) of LBW and, overall, 12% of the children exhibited below average performance on selected outcome measures. The below average school performance varied from 5-17% across the six selected areas of school performance. The highest rate of below average performance was observed in science (17%), followed by arithmetic and language (16% each). BW showed significant differential effects on school performance and behavioral outcomes, which remained significant after controlling for the effect of potential confounders. It was found that LBW children were 2-6 times more likely to have poorer school performance in all areas than their normal BW peers. . CONCLUSION: Early intervention programs or special care for LBW children in school could be an effective means of improving educational outcomes and the behavior of these children. Attempts should be made to reduce or prevent poor pregnancy outcomes, which, in turn, would reduce the cost of the health, education, and social services systems. PMID- 26366258 TI - Postoperative Nausea and Vomiting: Palonosetron with Dexamethasone vs. Ondansetron with Dexamethasone in Laparoscopic Hysterectomies. AB - OBJECTIVES: Postoperative nausea and vomiting (PONV) is the most common complication seen following laparoscopic surgery. Our study sought to evaluate the efficacy of the newer drug palonosetron with that of ondansetron, in combination with dexamethasone, for PONV in patients undergoing laparoscopic hysterectomies. . METHODS: A total of 90 patients, aged between 30-50 years old, posted for elective laparoscopic hysterectomies under general anesthesia belonging to the American Society of Anesthesiologist (ASA) physical status I and II were included in the study. Patients were randomly divided into one of two groups (n=45). Before induction, patients in the first group (group I) received 0.075mg palonosetron with 8mg dexamethasone and patients in the second group (group II) received 4mg ondansetron with 8mg dexamethasone. Postoperatively, any incidences of early or delayed vomiting, requirement of rescue antiemetic, and side effects were recorded. Patient's hemodynamics were also monitored. Statistical analysis was done using Student's t-test, chi-square test, and Fisher's exact test. . RESULTS: Preoperative, intraoperative, and postoperative heart rate, mean arterial pressure, peripheral capillary oxygen saturation were statistically not significant (p>0.050) in either group. In group II, eight patients had nausea in the first two hours and three patients had nausea in the two to six-hour postoperative period. In group I, three patients experienced nausea in the first six hours period. Eight patients in group II had vomited in the first two-hour period compared to one patient in group I (p=0.013). The requirement of rescue antiemetic was greater in group II than group I (20% vs. 4%). No side effects of antiemetic use were observed in either group. . CONCLUSION: The combination of palonosetron with dexamethasone is more effective in treating early, delayed, and long term PONV compared to ondansetron with dexamethasone in patients undergoing elective laparoscopic hysterectomies under general anesthesia. PMID- 26366259 TI - Effect of Two Different Doses of Dexmedetomidine as Adjuvant in Bupivacaine Induced Subarachnoid Block for Elective Abdominal Hysterectomy Operations: A Prospective, Double-blind, Randomized Controlled Study. AB - OBJECTIVES: Improvements in perioperative pain management for lower abdominal operations has been shown to reduce morbidity, induce early ambulation, and improve patients' long-term outcomes. Dexmedetomidine, a selective alpha-2 agonist, has recently been used intrathecally as adjuvant to spinal anesthesia to prolong its efficacy. We compared two different doses of dexmedetomidine added to hyperbaric bupivacaine for spinal anesthesia. The primary endpoints were the onset and duration of sensory and motor block, and duration of analgesia. . METHODS: A total of 100 patients, aged 35-60 years old, assigned to have elective abdominal hysterectomy under spinal anesthesia were divided into two equally sized groups (D5 and D10) in a randomized, double-blind fashion. The D5 group was intrathecally administered 3ml 0.5% hyperbaric bupivacaine with 5ug dexmedetomidine in 0.5ml of normal saline and the D10 group 3ml 0.5% bupivacaine with 10ug dexmedetomidine in 0.5ml of normal saline. For each patient, sensory and motor block onset times, block durations, time to first analgesic use, total analgesic need, postoperative visual analogue scale (VAS) scores, hemodynamics, and side effects were recorded. . RESULTS: Although both groups had a similar demographic profile, sensory and motor block in the D10 group (p<0.050) was earlier than the D5 group. Sensory and motor block duration and time to first analgesic use were significantly longer and the need for rescue analgesics was lower in the D10 group than the D5 group. The 24-hour VAS score was significantly lower in the D10 group (p<0.050). Intergroup hemodynamics were comparable (p>0.050) without any appreciable side effects. . CONCLUSION: Spinal dexmedetomidine increases the sensory and motor block duration and time to first analgesic use, and decreases analgesic consumption in a dose-dependent manner. PMID- 26366260 TI - Markers of Oxidative Stress in Pregnant Women with Sleep Disturbances. AB - OBJECTIVE: The quality and duration of sleep is impaired during pregnancy. Our study aimed to determine whether maternal sleep deprivation occurring during the second and third trimester of pregnancy could alter fetal well-being with respect to birth weight and APGAR score by altering the inflammatory status and oxidative stress in the mothers. . METHODS: Sleep adequacy was assessed using the Pittsburgh Sleep Quality Index (PSQI). We investigated the inflammatory status and oxidative stress at term in the blood of pregnant subjects with and without sleep deprivation by measuring the levels of protein-bound sialic acid (PBSA), high-sensitivity C-reactive protein (hsCRP), malondialdehyde (MDA) and protein carbonyl (PCO). Homocysteine (Hcy) and its vitamin determinants were also measured. Fetal outcome with respect to birth weight and APGAR score were compared between study subjects. . RESULTS: A significant increase was observed in the levels of hsCRP, PBSA, Hcy, MDA, and PCO, in the sleep-deprived group when compared to the control group. Fetal outcome at birth showed a significant difference between the cases with high sleep deprivation and those with low sleep deprivation. . CONCLUSION: Sleep deprivation in pregnancy leads to an increase in the inflammatory parameters, oxidative stress, and Hcy levels. Fetal outcome at birth was affected more in mothers with high sleep deprivation than those with low sleep deprivation. Follow-up in these babies are needed to reveal any differences in their growth and development. PMID- 26366261 TI - Prevalence of Device-associated Nosocomial Infections Caused By Gram-negative Bacteria in a Trauma Intensive Care Unit in Libya. AB - OBJECTIVES: Device-associated nosocomial infections (DANIs) have a major impact on patient morbidity and mortality. Our study aimed to determine the distribution rate of DANIs and causative agents and patterns of antibiotic resistance in the trauma-surgical intensive care unit (ICU). . METHODS: Our study was conducted at Abusalim Trauma Hospital in Tripoli, Libya. All devices associated with nosocomial infections, including central venous catheters (CVC), endotracheal tubes (ETT), Foley's urinary catheters, chest tubes, nasogastric tubes (NGT), and tracheostomy tubes, were removed aseptically and examined for Gram-negative bacteria (GNB). . RESULTS: During a one-year study period, 363 patients were hospitalized; the overall mortality rate was 29%. A total of 79 DANIs were identified, the most common site of infection was ETT (39.2%), followed by urinary catheters (19%), NGTs (18%), tracheostomy tubes (11%), CVCs (10%), and chest tubes (3%). The most frequently isolated organisms were Klebsiella pneumonia, Acinetobacter baumannii, and Pseudomonas aeruginosa (30%, 20%, and 14%, respectively). Extremely high resistance rates were observed among GNB to ampicillin (99%), cefuroxime (95%), amoxicillin-clavulante (92%), and nitrofurantoin (91%). Lower levels of resistance were exhibited to amikacin (38%), imipenem (38%), and colistin (29%). About 39% of the isolates were defined as multi-drug resistant (MDR). Overall, extended spectrum beta-lactmase producers were expressed in 39% of isolates mainly among K. pneumonia (88%). A. baumannii isolates exhibited extremely high levels of resistance to all antibiotics except colistin (100% sensitive). In addition, 56.3% of A. baumannii isolates were found to be MDR. P. aeruginosa isolates showed 46%-55% effectiveness to anti pseudomonas antibiotics. . CONCLUSION: High rates of DANI's and the emergence of MDR organisms poses a serious threat to patients. There is a need to strengthen infection control within the ICU environment, introduce surveillance systems, and implement evidence-based preventive strategies. PMID- 26366262 TI - Nurses Use of Critical Care Pain Observational Tool in Patients with Low Consciousness. AB - OBJECTIVES: The diagnosis of pain in patients with low consciousness is a major challenge in the intensive care unit (ICU). Therefore, the use of behavioral tools for pain assessment could be an effective tool to manage pain in this group of patients. The aim of this study was to determine the effects on pain management by nurses using a critical care pain observational tool in patients with a decreased level of consciousness. . METHODS: Our research used a before and after design to evaluate the ability of nurses to manage pain in patients with low consciousness. A total of 106 ICU nurses were included in the study. The study was divided into three phases: pre-implementation, implementation, and post implementation. The researchers first observed the nurses management of pain in their patients; this was done three times using a checklist following tracheal suctioning and position change procedures. The nurses were then taught how to apply the critical-care pain observational tool (CPOT). Post-implementation of the tool, the researchers re-evaluated trained the nurses' pain management. . RESULTS: Performance scores after training improved with relation to the nurses diagnosis of pain, pharmacological and nonpharmacological actions, reassessment of pain, and re-relieving of any pain. However, use of the tool did not improve the recording of the patient's pain and the relief measures used. . CONCLUSION: Use of the CPOT can increase nurse's sensitivity to pain in non-conscious patients and drive them to track and perform pain management. PMID- 26366263 TI - Prevalence of Enterotoxin Genes and Antibacterial Susceptibility Pattern of Staphylococcus aureus Strains Isolated from Animal Originated Foods in West of Iran. AB - OBJECTIVES: The aims of our study were to evaluate the prevalence of Staphylococcus aureus (S. aureus) strains in food samples of animal origin, examine their antibacterial susceptibility pattern, and to detect staphylococcal enterotoxin (SEs) genes and the mecA gene in isolated S. aureus strains using the polymerase chain reaction (PCR). . METHODS: A total of 1050 food samples including 671 raw milk and dairy products and 379 raw meats were collected between September 2013 and June 2014 in Hamadan, Iran. Food samples were analyzed for S. aureus identification. The antibiotic susceptibility pattern of all isolates was determined using the disk agar diffusion method followed by detecting mecA resistance gene using PCR. In addition, harboring of SE genes were determined using a multiplex PCR assay targeting nine genes. . RESULTS: A total of 98 (9.3%) S. aureus strains were isolated from 1050 food samples. Of the 98 isolates examined, the most frequent resistance was observed to erythromycin (30.6%), followed by tetracycline (29.6%), gentamicin (27.6%), clindamycin (26.5%), ciprofloxacin and rifampin (24.5%), trimethoprim-sulfamethoxazole (14.3%), and cefoxitin (5.1%). All cefoxitin resistant isolates were positive for mecA. The prevalence of SEs was 77.6% (n=76). Among the genes that code classic enterotoxins, sea was the most frequent and was carried by 25.5% of isolates, followed by see in 18.4%, sed in 11.2%, sec in 5.1%, and seb in 4.1% of isolates. Among the detected enterotoxins, seg was the predominantly identified enterotoxin gene in isolates with prevalence of 35.7%. The seh gene with prevalence of 1% and sei gene with 3.1% were other detected enterotoxins with low frequencies. . CONCLUSION: The high prevalence of SE genes detected indicates a potential risk for causing animal-originated food poisoning. The increasing prevalence of community-acquired MRSA and its emerging antibiotic resistance in foods is a serious problem for public health. PMID- 26366264 TI - Potassium Permanganate Poisoning: A Nonfatal Outcome. AB - Acute poisoning by potassium permanganate is a rare condition with high morbidity and mortality. Diagnosis of the condition relies on a history of exposure or ingestion and a high degree of clinical suspicion. Oxygen desaturation and the presence of methemoglobin are also helpful indicators. Since no specific antidote is available, treatment is mainly supportive. Few cases have been reported in the literature following potassium permanganate ingestion, whether intentional or accidental, and most of the patients in these cases had unfavorable outcomes, which was not the case in our patient. Our patient, a 73-year-old male, purchased potassium permanganate over the counter mistaking it for magnesium salt, which he frequently used as a laxative. Several hours after he ingested it, he was admitted to the endocrine department at King Hussein Medical Center, Jordan, with acute rapidly evolving shortness of breath. During hospitalization, his liver function tests deteriorated. Since he was diagnosed early and managed promptly he had a favorable outcome. PMID- 26366265 TI - Epithelioid Hemangioendothelioma of Tibia and Talus: A Case Report. AB - Epithelioid hemangioendothelioma (EHE) of the bone is extremely uncommon and consists of less than 1% of primary bone tumors. It is characterized by epithelioid endothelial cells and has variable biological behavior. EHE is more likely to occur between 20 and 30 years of age. Approximately half of EHE present with multifocal disease. Since the behavior of these tumors is intermediate, it is important to not misdiagnose EHE as an angiosarcoma. Here we describe the case of a 43-year-old male who presented with pain and swelling of the leg and ankle to Dr. Ram Manohar Lohia Hospital, India. Radiography and computed tomography of the ankle and leg were performed and suggested an expansile lytic lesion involving the distal tibia and talus bone. The lesion was excised and ankle arthrodesis performed. Histological evaluation of the lesion demonstrated the presence of EHE of the tibia and talus. PMID- 26366266 TI - Two Cases of Pneumatoceles in Mechanically Ventilated Infants. AB - Pulmonary pneumatocele is a thin-walled, gas-filled space within the lung that usually occurs in association with bacterial pneumonia and is usually transient. The majority of pneumatoceles resolve spontaneously without active intervention, but in some cases they might lead to pneumothorax with subsequent hemodynamic instability. We report two cases presented to the pediatric intensive care unit at the Royal Hospital, Oman with pneumatoceles. The first was a 14-day-old baby who underwent surgical repair of total anomalous pulmonary venous connection (TAPVC) requiring extracorporeal membrane oxygenation (ECMO) support following surgery. He was initially on conventional mechanical ventilation. Seven days after the surgery, he started to develop bilateral pneumatoceles. The pneumatoceles were not regressing and they did not respond to three weeks of conservative management with high-frequency oscillation ventilation (HFOV). He failed four attempts of weaning from HFOV to conventional ventilation. Each time he was developing tachypnea and carbon dioxide retention. Percutaneous intercostal chest drain (ICD) insertion was needed to evacuate one large pneumatocele. Subsequently, he improved and we were able to wean and extubate him. The second case was a two-month-old male admitted with severe respiratory distress secondary to respiratory syncytial virus (RSV) pneumonitis. After intubation, he required a high conventional ventilation setting and within 24 hours he was on HFOV. Conservative management with HFOV was sufficient to treat the pneumatoceles and no further intervention was needed. Our cases demonstrate two different approaches in the management of pneumatoceles in mechanically ventilated children. Each approach was case dependent and could not be used interchangeably. PMID- 26366267 TI - Nasal Angioleiomyoma: An Unusual Cause of Epistaxis. AB - Angioleiomyomas are infrequent benign tumors originating from smooth muscle cells of arterial or venous walls. They are most commonly seen in the lower extremities with a prevalence of only 8.5% in the head and neck. We present the case of a 40 year-old male patient who presented to Christian Medical College, Vellore, India, with recurrent episodes of right-sided epistaxis. A computed tomography scan showed an enlarged right inferior turbinate filling the right nasal cavity. The mass was removed endoscopically and sent to pathology. A diagnosis of angioleiomyoma of the nasal cavity was made. This location that has only been described in a minority of cases in the literature. Our case report signifies the importance of maintaining a broad differential when dealing with patients presenting with nasal mass and the importance of histopathological examination for the diagnosis. PMID- 26366268 TI - Penile Soft Tissue Swelling. PMID- 26366269 TI - Switching to Multiple Daily Insulin Injections in Children and Adolescents with Type 1 Diabetes: A Question of Standards. PMID- 26366270 TI - Letter in Reply: A Question of Standards. PMID- 26366271 TI - Genetic classifiers for prostate cancer: A new era on the horizon? PMID- 26366272 TI - National nephrectomy registries: Reviewing the need for population-based data. AB - Nephrectomy is the cornerstone therapy for renal cell carcinoma (RCC) and continued refinement of the procedure through research may enhance patient outcomes. A national nephrectomy registry may provide the key information needed to assess the procedure at a national level. The aim of this study was to review nephrectomy data available at a population-based level in Australia and to benchmark these data against data from the rest of the world as an examination of the national nephrectomy registry model. A PubMed search identified records pertaining to RCC nephrectomy in Australia. A similar search identified records relating to established nephrectomy registries internationally and other surgical registries of clinical importance. These records were reviewed to address the stated aims of this article. Population-based data within Australia for nephrectomy were lacking. Key issues identified were the difficulty in benchmarking outcomes and no ongoing monitoring of trends. The care centralization debate, which questions whether small-volume centers provide comparable outcomes to high-volume centers, is ongoing. Patterns of adherence and the effectiveness of existing protocols are uncertain. A review of established international registries demonstrated that the registry model can effectively address issues comparable to those identified in the Australian literature. A national nephrectomy registry could address deficiencies identified in a given nation's nephrectomy field. The model is supported by evidence from international examples and will provide the population-based data needed for studies. Scope exists for possible integration with other registries to develop a more encompassing urological or surgical registry. Need remains for further exploration of the feasibility and practicalities of initiating such a registry including a minimum data set, outcome indicators, and auditing of data. PMID- 26366273 TI - Recent advancement or less invasive treatment of percutaneous nephrolithotomy. AB - Since its initial introduction in 1976, percutaneous nephrolithotomy (PCNL) has been widely performed for the management of large renal stones and currently is recommended for staghorn calculi, kidney stones larger than 2 cm, and shock wave lithotripsy-resistant lower pole stones greater than 1 cm. However, except for open and laparoscopic surgery, PCNL is the most invasive of the minimally invasive stone surgery techniques. Over the years, technical and instrumental advances have been made in PCNL to reduce morbidity and improve effectiveness. A thorough review of the recent literature identified five major areas of progress for the advancement of PCNL: patient positioning, method of percutaneous access, development of lithotriptors, miniaturized access tracts, and postoperative nephrostomy tube management. This review provides an overview of recent advancements in PCNL and the outcomes of each area of progress and notes how much we achieve with less invasive PCNL. This information may allow us to consider the future role and future developments of PCNL. PMID- 26366274 TI - Pathological upgrading in prostate cancer patients eligible for active surveillance: Does prostate-specific antigen density matter? AB - PURPOSE: To evaluate prospectively the role of prostate-specific antigen (PSA) density in predicting Gleason score upgrading in prostate cancer patients eligible for active surveillance (T1/T2, biopsy Gleason score<=6, PSA<=10 ng/mL, and <=2 positive biopsy cores). MATERIALS AND METHODS: Between January 2010 and November 2013, among patients who underwent greater than 10-core transrectal ultrasound-guided biopsy, 60 patients eligible for active surveillance underwent radical prostatectomy. By use of the modified Gleason criteria, the tumor grade of the surgical specimens was examined and compared with the biopsy results. RESULTS: Tumor upgrading occurred in 24 patients (40.0%). Extracapsular disease and positive surgical margins were found in 6 patients (10.0%) and 8 patients (17.30%), respectively. A statistically significant correlation between PSA density and postoperative upgrading was found (p=0.030); this was in contrast with the other studied parameters, which failed to reach significance, including PSA, prostate volume, number of biopsy cores, and number of positive cores. Tumor upgrading was also highly associated with extracapsular cancer extension (p=0.000). The estimated optimal cutoff value of PSA density was 0.13 ng/mL(2), obtained by receiver operating characteristic analysis (area under the curve=0.66; p=0.020; 95% confidence interval, 0.53-0.78). CONCLUSIONS: PSA density is a strong predictor of Gleason score upgrading after radical prostatectomy in patients eligible for active surveillance. Because tumor upgrading increases the potential for postoperative pathological adverse findings and prognosis, PSA density should be considered when treating and consulting patients eligible for active surveillance. PMID- 26366275 TI - Effects of statin use on the response duration to androgen deprivation therapy in metastatic prostate cancer. AB - PURPOSE: To determine whether statin use delays the development of castration resistant prostate cancer (CRPC) in patients with metastatic prostate cancer treated with androgen deprivation therapy (ADT). MATERIALS AND METHODS: A total of 171 patients with metastatic prostate cancer at the time of diagnosis who were treated with ADT between January 1997 and December 2013 were retrospectively analyzed. The patients were classified into two groups: the nonstatin use group (A group) and the statin use group (B group). Multivariate analysis was performed on statin use and other factors considered likely to have an effect on the time to progression to CRPC. RESULTS: The mean patient age was 67.1+/-9.1 years, and the mean follow-up period was 52 months. The mean initial prostate-specific antigen (PSA) level was 537 ng/mL. Of the 171 patients, 125 (73%) were in group A and 46 (27%) were in group B. The time to progression to CRPC was 22.7 months in group A and 30.5 months in group B, and this difference was significant (p=0.032). Blood cholesterol and initial PSA levels did not differ significantly according to the time to progression to CRPC (p=0.288, p=0.198). Multivariate analysis using the Cox regression method showed that not having diabetes (p=0.037) and using a statin (p=0.045) significantly increased the odds ratio of a longer progression to CRPC. CONCLUSIONS: Statin use in metastatic prostate cancer patients appears to delay the progression to CRPC. Large-scale, long-term follow-up studies are needed to validate this finding. PMID- 26366276 TI - Difference in the rate of rectal complications following prostate brachytherapy based on the prostate-rectum distance and the prostate longitudinal length among early prostate cancer patients. AB - PURPOSE: To investigate the difference in rectal complications rate following prostate low dose rate (LDR) brachytherapy based on prostate-rectum distance and prostate longitudinal length among early prostate cancer patients. MATERIALS AND METHODS: From March 2008 to February 2013, 245 prostate cancer patients with a Gleason score <=7 were treated with 125-I LDR brachytherapy. Among them, 178 patients with prostate volume 20-35 mL and a follow-up period >=6 months were evaluated for radiation proctitis. Magnetic resonance imaging (MRI) was performed for a prebrachytherapy evaluation, and prostate-rectum distance and prostate longitudinal length were measured. The radiation proctitis was confirmed and graded via colonoscopy based on the radiation therapy oncology group (RTOG) toxicity criteria. RESULTS: Twenty-three patients received a colonoscopy for proctitis evaluation, and 12 were identified as grade 1 on the RTOG scale. Nine patients were diagnosed as grade 2 and 2 patients were grade 3. No patient developed grade 4 proctitis. The rectal-complication group had a mean prostate rectum distance of 2.51+/-0.16 mm, while non-rectal-complication control group had 3.32+/-0.31 mm. The grade 1 proctitis patients had a mean prostate-rectum distance of 2.80+/-0.15 mm, which was significantly longer than 2.12+/-0.31 mm of grades 2 and 3 patient groups (p=0.045). All 11 patients of grades 2 and 3 had a prostate longitudinal length of 35.22+/-2.50 mm, which was longer than group 1, but the difference was not statistically significant (p=0.214). CONCLUSIONS: As the prostate-rectum distance increased, fewer postimplantation rectal symptoms were observed. Patients with a shorter prostate-rectum distance in MRI should receive modified implantation techniques or radical prostatectomy. PMID- 26366277 TI - Can a dual-energy computed tomography predict unsuitable stone components for extracorporeal shock wave lithotripsy? AB - PURPOSE: To assess the potential of dual-energy computed tomography (DECT) to identify urinary stone components, particularly uric acid and calcium oxalate monohydrate, which are unsuitable for extracorporeal shock wave lithotripsy (ESWL). MATERIALS AND METHODS: This clinical study included 246 patients who underwent removal of urinary stones and an analysis of stone components between November 2009 and August 2013. All patients received preoperative DECT using two energy values (80 kVp and 140 kVp). Hounsfield units (HU) were measured and matched to the stone component. RESULTS: Significant differences in HU values were observed between uric acid and nonuric acid stones at the 80 and 140 kVp energy values (p<0.001). All uric acid stones were red on color-coded DECT images, whereas 96.3% of the nonuric acid stones were blue. Patients with calcium oxalate stones were divided into two groups according to the amount of monohydrate (calcium oxalate monohydrate group: monohydrate>=90%, calcium oxalate dihydrate group: monohydrate<90%). Significant differences in HU values were detected between the two groups at both energy values (p<0.001). CONCLUSIONS: DECT improved the characterization of urinary stone components and was a useful method for identifying uric acid and calcium oxalate monohydrate stones, which are unsuitable for ESWL. PMID- 26366278 TI - Efficacy of mitomycin C in reducing recurrence of anterior urethral stricture after internal optical urethrotomy. AB - PURPOSE: To determine the efficacy of mitomycin C in reducing the recurrence of anterior urethral stricture after internal optical urethrotomy (IOU). MATERIALS AND METHODS: This was a randomized controlled trial conducted in the Department of Urology at the Institute of Kidney Diseases Peshawar from March 2011 to December 2013. A total of 151 patients who completed the study were divided into two groups by the lottery method. Group A (cases) comprised 78 patients in whom mitomycin C 0.1% was injected submucosally in the stricture after conventional IOU. Group B (controls) comprised 73 patients in whom IOU only was performed. Self-clean intermittent catheterization was not offered in either group. All patients were regularly followed up for 18 months. Recurrence was diagnosed by use of retrograde urethrogram in all patients and flexible urethroscopy in selected cases. Data were collected on a structured pro forma sheet and were analyzed by SPSS. RESULTS: The mean age of the patients in group A was 37.31+/ 10.1 years and that in group B was 40.1+/-11.4 years. Recurrence of urethral stricture was recorded in 11 patients (14.1%) in group A and in 27 patients (36.9%) in group B (p=0.002). The mitomycin group also showed a delay in recurrence compared with the control group (p=0.002). CONCLUSIONS: Recurrence of urethral stricture is high after optical urethrotomy. Mitomycin C was found to be highly effective in preventing the recurrence of urethral stricture after IOU. PMID- 26366279 TI - Effect of curcumin on the interaction between androgen receptor and Wnt/beta catenin in LNCaP xenografts. AB - PURPOSE: Curcumin is a nontoxic, chemopreventive agent possessing multifaceted functions. Our previous study showed that curcumin inhibits androgen receptor (AR) through modulation of Wnt/beta-catenin signaling in LNCaP cells. Therefore, we investigated the in vivo effects of curcumin by using LNCaP xenografts. MATERIALS AND METHODS: LNCaP cells were subcutaneously inoculated in Balb/c nude mice. When the tumor volume reached greater than 100 mm(3), either curcumin (500 mg/kg body weight) or vehicle was administered through oral gavage three times weekly for 4 weeks. The expression of AR and intermediate products of Wnt/beta catenin were assessed. RESULTS: Curcumin had an inhibitory effect on tumor growth during the early period, which was followed by a slow increase in growth over time. Tumor growth was delayed about 27% in the curcumin group. The mean prostate specific antigen (PSA) doubling time in the curcumin group was approximately twice that in the untreated group. Curcumin significantly decreased AR expression at both the mRNA and protein level. The PSA levels tended to be reduced in the curcumin group. However, there were no significant changes in expression of Wnt/beta-catenin pathway intermediates. CONCLUSIONS: This study revealed that curcumin initially interferes with prostate cancer growth by inhibiting AR activity and possibly by reducing PSA expression. Further research is needed to investigate the plausible mechanism of the antiandrogenic action of curcumin. PMID- 26366280 TI - Needle tract seeding following percutaneous biopsy of renal cell carcinoma. AB - A 66-year-old man underwent computed tomography-guided needle biopsy of a suspicious renal mass. Two months later he underwent partial nephrectomy. Histology revealed a 30-mm clear cell renal cell carcinoma, up to Fuhrman grade 3. An area of the capsule was interrupted, which corresponded to a hemorrhagic area on the cortical surface. Under microscopy, this area showed a tongue of tumor tissue protruding through the renal capsule. A tumor deposit was found in the perinephric fat. These features suggest that tumor seeding may have occurred during the needle biopsy. PMID- 26366281 TI - Corrigendum: Inpatient hypospadias care: Trends and outcomes from the American nationwide inpatient sample. AB - [This corrects the article on p. 594 in vol. 56, PMID: 26279829.]. PMID- 26366282 TI - Triptycene-based small molecules modulate (CAG).(CTG) repeat junctions. AB - Nucleic acid three-way junctions (3WJs) play key roles in biological processes such as nucleic acid replication in addition to being implicated as dynamic transient intermediates in trinucleotide repeat sequences. Structural modulation of specific nucleic acid junctions could allow for control of biological processes and disease states at the nucleic acid level. Trinucleotide repeat expansions are associated with several neurodegenerative diseases where dynamic slippage is thought to occur during replication, forming transient 3WJ intermediates with the complementary strand. Here, we report triptycene-based molecules that bind to a d(CAG).(CTG) repeat using a gel shift assay, fluorescence-quenching and circular dichroism. PMID- 26366283 TI - Tylosin polyketide synthase module 3: stereospecificity, stereoselectivity and steady-state kinetic analysis of beta-processing domains via diffusible, synthetic substrates. AB - Polyketide synthase (PKS) beta-processing domains are responsible for much of the stereochemical complexity of polyketide natural products. Although the importance of beta-processing domains has been well noted and significantly explored, key stereochemical details pertaining to cryptic stereochemistry and the impact of remote stereogenic centers have yet to be fully discerned. To uncover the inner workings of ketoreductases (KR) and dehydratases (DH) from the tylosin pathway a didomain composed of TylDH3-KR3 was recombinantly expressed and interrogated with full-length tetraketide substrates to probe the impact of vicinal and distal stereochemistry. In vitro product isolation analysis revealed the products of the cryptic KR as d-alcohols and of the DH as trans-olefins. Steady-state kinetic analysis of the dehydration reaction demonstrated a strict stereochemical tolerance at the beta-position as d-configured substrates were processed more than 100 times more efficiently than l-alcohols. Unexpectedly, the kcat/KM values were diminished 14- to 45-fold upon inversion of remote epsilon- and zeta stereocenters. This stereochemical discrimination is predicted to be driven by a combination of allylic A1,3 strain that likely disfavors binding of the epsilon epimer and a loss of electrostatic interactions with the zeta-epimer. Our results strongly suggest that dehydratases may play a role in refining the stereochemical outcomes of preceding modules through their substrate stereospecificity, honing the configurational purity of the final PKS product. PMID- 26366284 TI - New Approaches for Biomonitoring Exposure to the Human Carcinogen Aristolochic Acid. AB - Aristolochic acids (AA) are found in all Aristolochia herbaceous plants, many of which have been used worldwide for medicinal purposes for centuries. AA are causal agents of the chronic kidney disease entity termed aristolochic acid nephropathy (AAN) and potent upper urinary tract carcinogens in humans. AAN and upper urinary tract cancers are endemic in rural areas of Croatia and other Balkan countries where exposure to AA occurs through the ingestion of home-baked bread contaminated with Aristolochia seeds. In Asia, exposure to AA occurs through usage of traditional Chinese medicinal herbs containing Aristolochia. Despite warnings from regulatory agencies, traditional Chinese herbs containing AA continue to be used world-wide. In this review, we highlight novel approaches to quantify exposure to AA, by analysis of aristolactam (AL) DNA adducts, employing ultraperformance liquid chromatography-electrospray ionization/multistage mass spectrometry (UPLC-ESI/MSn). DNA adducts are a measure of internal exposure to AA and serve as an important end point for cross-species extrapolation of toxicity data and human risk assessment. The level of sensitivity of UPLC-ESI/MSn surpasses the limits of detection of AL-DNA adducts obtained by 32P-postlabeling techniques, the most widely employed methods for detecting putative DNA adducts in humans. AL-DNA adducts can be measured by UPLC ESI/MS3, not only in fresh frozen renal tissue, but also in formalin-fixed, paraffin-embedded (FFPE) samples, an underutilized biospecimen for assessing chemical exposures, and in exfoliated urinary cells, a non-invasive approach. The frequent detection of AL DNA adducts in renal tissues, combined with the characteristic mutational spectrum induced by AA in TP53 and other genes provides compelling data for a role of AA in upper urothelial tract cancer. PMID- 26366285 TI - Do MRI findings identify patients with chronic low back pain and Modic changes who respond best to rest or exercise: a subgroup analysis of a randomised controlled trial. AB - BACKGROUND: No previous clinical trials have investigated MRI findings as effect modifiers for conservative treatment of low back pain. This hypothesis-setting study investigated if MRI findings modified response to rest compared with exercise in patients with chronic low back pain and Modic changes. METHODS: This study is a secondary analysis of a randomised controlled trial comparing rest with exercise. Patients were recruited from a specialised outpatient spine clinic and included in a clinical trial if they had chronic low back pain and an MRI showing Modic changes. All patients received conservative treatment while participating in the trial. Five baseline MRI findings were investigated as effect modifiers: Modic changes Type 1 (any size), large Modic changes (any type), large Modic changes Type 1, severe disc degeneration and large disc herniation. The outcome measure was change in low back pain intensity measured on a 0-10 point numerical rating scale at 14-month follow-up (n = 96). An interaction >= 1.0 point (0-10 scale) between treatment group and MRI findings in linear regression was considered clinically important. RESULTS: The interactions for Modic Type 1, with large Modic changes or with large Modic changes Type 1 were all potentially important in size (-0.99 (95 % CI -3.28 to 1.29), -1.49 ( 3.73 to 0.75), -1.49 (-3.57 to 0.58), respectively) but the direction of the effect was the opposite to what we had hypothesized-that people with these findings would benefit more from rest than from exercise. The interactions for severe disc degeneration (0.74 (-1.40 to 2.88)) and large disc herniation (-0.92 (3.15 to 1.31)) were less than the 1.0-point threshold for clinical importance. As expected, because of the lack of statistical power, no interaction term for any of the MRI findings was statistically significant. CONCLUSIONS: Three of the five MRI predictors showed potentially important effect modification, although the direction of the effect was surprising and confidence intervals were wide so very cautious interpretation is required. Further studies with adequate power are warranted to study these and additional MRI findings as potential effect modifiers for common interventions. PMID- 26366286 TI - Adoptive T-cell therapy for fungal infections in haematology patients. AB - The prolonged immune deficiency resulting from haematopoietic stem cell transplant and chemotherapy predisposes to a high risk of invasive fungal infections. Despite the recent advances in molecular diagnostic testing, early initiation of pre-emptive antifungal therapy and the use of combination pharmacotherapy, mortality from invasive mould infections remain high among recipients of allogeneic stem cell transplant. The increasing incidences of previously rare and drug-resistant strains of fungi present a further clinical challenge. Therefore, there is a need for novel strategies to combat fungal infections in the immunocompromised. Adoptive therapy using in vitro-expanded fungus-specific CD4 cells of the Th-1 type has shown clinical efficacy in murine studies and in a small human clinical study. Several techniques for the isolation and expansion of fungus-specific T cells have been successfully applied. Here we discuss the incidence and changing patterns of invasive fungal diseases, clinical evidence supporting the role of T cells in fungal immunity, methods to expand fungus-specific T cells in the laboratory and considerations surrounding the use of T cells for fungal immunotherapy. PMID- 26366287 TI - Expression profiling pre-diabetic mice to uncover drugs with clinical application to type 1 diabetes. AB - In the NOD mouse model of type 1 diabetes (T1D), genetically identical mice in the same environment develop diabetes at different rates. Similar heterogeneity in the rate of progression to T1D exists in humans, but the underlying mechanisms are unclear. Here, we aimed to discover peripheral blood (PB) genes in NOD mice predicting insulitis severity and rate of progression to diabetes. We then wished to use these genes to mine existing databases to identify drugs effective in diabetes. In a longitudinal study, we analyzed gene expression in PB samples from NOD.CD45.2 mice at 10 weeks of age, then scored pancreatic insulitis at 14 weeks or determined age of diabetes onset. In a multilinear regression model, Tnf and Tgfb mRNA expression in PB predicted insulitis score (R (2)=0.56, P=0.01). Expression of these genes did not predict age of diabetes onset. However, by expression-profiling PB genes in 10-week-old NOD.CD45.2 mice, we found a signature of upregulated genes that predicted delayed or no diabetes. Major associated pathways included chromatin organization, cellular protein location and regulation of nitrogen compounds and RNA. In a clinical cohort, three of these genes were differentially expressed between first-degree relatives, T1D patients and controls. Bioinformatic analysis of differentially expressed genes in NOD.CD45.2 PB identified drugs that are predicted to delay or prevent diabetes. Of these drugs, 11 overlapped with drugs predicted to induce a human 'non-progressor' expression profile. These data demonstrate that disease heterogeneity in diabetes-prone mice can be exploited to mine novel clinical T1D biomarkers and drug targets. PMID- 26366288 TI - T2-based temperature monitoring in abdominal fat during MR-guided focused ultrasound treatment of patients with uterine fibroids. AB - BACKGROUND: Near-field heating is a potential problem in focused ultrasound treatments, as it can result in thermal injury to skin, subcutaneous fat, and other tissues. Our goals were to determine if T2-based temperature mapping could be used reliably to measure near-field heating in adipose tissue and whether it is practical to perform such mapping during focused ultrasound treatments. METHODS: We investigated the dependence of T2 on temperature in ex vivo adipose tissue at 3T using a double-echo fast spin echo (FSE) sequence. We implemented and evaluated the T2-based temperature mapping technique in the adipose tissue of two healthy volunteers. Finally, we applied the technique during magnetic resonance-guided focused ultrasound (MRgFUS) treatments to measure near-field heating in eight patients with uterine fibroids. RESULTS: Calibration experiments in porcine adipose tissue determined a temperature coefficient of 6.16 ms/ degrees C during heating and 5.37 ms/ degrees C during cooling. The volunteer experiments demonstrated a strong correlation between the skin temperature and T2 based temperature measurements in the fat layer. During the treatments of patients with uterine fibroids, we observed a measurable change in the T2 of fat tissue within the path of the ultrasound beam and a temperature increase of up to 15 degrees C with sustained heating of more than 10 degrees C. CONCLUSIONS: Our results demonstrate the feasibility and importance of monitoring near-field heating in fatty tissues. The implementation of near-field monitoring between sonications can shorten treatments by reducing the cooling time. It can help improve safety by avoiding excessive heating in the near field. PMID- 26366289 TI - Stability, cytotoxicity and cell uptake of water-soluble dendron-conjugated gold nanoparticles with 3, 12 and 17 nm cores. AB - This article describes the synthesis of water-soluble dendron-conjugated gold nanoparticles (Den-AuNPs) with various average core sizes and the evaluation of stability, cytotoxicity, cell permeability and uptake of these materials. The characterization of Den-AuNPs using various techniques including transmission electron microscopy (TEM), matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS), 1H NMR, FT-IR, and UV-vis spectroscopy confirms the dendron conjugation to the glutathione-capped gold nanoparticles (AuNPs). The stability of AuNPs and Den-AuNPs in solutions of different pH and salt concentration is determined by monitoring the changes in surface plasmon bands of gold using UV-vis spectroscopy. The stability of Den-AuNPs at different pH remained about the same compared to that of AuNPs. In comparison, the Den AuNPs are found to be more stable than the precursor AuNPs maintaining their solubility in the aqueous solution with the salt concentration of up to 100 mM. The improved stability of Den-AuNPs suggests that the post-functionalization of thiol-capped gold nanoparticle surfaces with dendrons can further improve the physiological stability and biocompatibility of gold nanoparticle-based materials. Cytotoxicity studies of AuNPs and Den-AuNPs with and without fluorophores are also performed by examining cell viability for 3T3 fibroblasts using a MTT cell proliferation assay. The conjugation of dendrons to the AuNPs with a fluorophore is able to decrease the cytotoxicity brought about by the fluorophore. The successful uptake of Den-AuNPs in mouse fibroblast 3T3 cells shows the physiological viability of the hybrid materials. PMID- 26366290 TI - Latent Factor Structure of DSM-5 Posttraumatic Stress Disorder. AB - The current study examined the latent factor structure of posttraumatic stress disorder (PTSD) based on DSM-5 criteria in a sample of participants (N = 374) recruited for studies on trauma and health. Confirmatory factor analyses (CFA) were used to compare the fit of the previous 3-factor DSM-IV model of PTSD to the 4-factor model specified in DSM-5 as well as to a competing 4-factor "dysphoria" model (Simms, Watson, & Doebbeling, 2002) and a 5-factor (Elhai et al., 2011) model of PTSD. Results indicated that the Elhai 5-factor model (re-experiencing, active avoidance, emotional numbing, dysphoric arousal, anxious arousal) provided the best fit to the data, although substantial support was demonstrated for the DSM-5 4-factor model. Low factor loadings were noted for two of the symptoms in the DSM-5 model (psychogenic amnesia and reckless/self-destructive behavior), which raises questions regarding the adequacy of fit of these symptoms with other core features of the disorder. Overall, the findings from the present research suggest the DSM-5 model of PTSD is a significant improvement over the previous DSM-IV model of PTSD. PMID- 26366291 TI - At what level of unconsciousness is mild therapeutic hypothermia indicated for out-of-hospital cardiac arrest: a retrospective, historical cohort study. AB - BACKGROUND: Appropriate patient selection is very important when initiating mild therapeutic hypothermia (MTH) for patients following out-of-hospital cardiac arrest, and the extent of unconsciousness at implementation must be defined in such cases. However, there are no clear standards regarding the level of unconsciousness at which MTH would be beneficial. The effects of MTH in patients with different degrees of unconsciousness according to the motor response score of the Glasgow Coma Scale (GCS) were investigated. METHODS: The subjects consisted of witnessed non-traumatic adult out-of-hospital cardiac arrest patients admitted to our institute from April 2002 to August 2011. The patients were divided into six groups according to the GCS motor response score: 1 (GCS M1), 2 (GCS M2), 3 (GCS M3), 4 (GCS M4), 5 (GCS M5), and 6 (GCS M6). The neurological outcome was evaluated at 30 days after hospital admission using the Cerebral Performance Category. Chi-squared Automatic Interaction Detection (CHAID) analysis was performed to estimate the threshold GCS M level where therapeutic hypothermia is indicated. Odds ratios were then calculated by multiple logistic-regression analysis using factors including GCS M5-6 and MTH. RESULTS: A total of 289 patients were enrolled in this study. CHAID analysis demonstrated two points of significant increase in percentage of good recovery at 30 days after admission, dividing the GCS M categories into three groups. Patients classified with a GCS motor response score of 5 or higher had the highest percentage of good recovery. The odds ratio for good recovery (CPC1-2) was 2.901 (95 % CI 1.460-5.763, P = 0.002) for MTH, and that for GCS M5-6 was 159.835 (95 % CI 33.592-760.513, P < 0.001). CONCLUSIONS: MTH may be unnecessary in patients with a GCS motor response score of 5 or higher. Consequently, because there are post cardiac arrest patients with a GCS motor response score of 4 or lower who benefit from MTH, MTH may be limited to patients with a GCS motor response score of 4 or lower. PMID- 26366292 TI - A unique biofilm in human deep mycoses: fungal amyloid is bound by host serum amyloid P component. AB - BACKGROUND/OBJECTIVES: We have demonstrated the presence of Candida cell surface amyloids that are important in aggregation of fungi and adherence to tissue. Fungal amyloid was present in invasive human candidal infections and host serum amyloid P component (SAP) bound to the fungal amyloid. SAP is a protease resistant glycoprotein that binds avidly to amyloid and interferes with host defence, especially against bacterial pathogens for which neutrophils are important. In this study, we investigated whether biofilm of fungal amyloid and SAP was a feature of other disseminated fungal infections. METHODS: Tissue specimens from 15 autopsies were systematically evaluated with multiple histochemical stains including thioflavin T and Congo red (dyes that stain amyloid), as well as antibody to SAP. We studied specimens with disseminated aspergillosis, mucormycosis and coccidioidomycosis. The structure of the lesions, host inflammatory cells and the presence of fungal amyloid and SAP were determined. RESULTS: The structure of the lesions was characteristic in aspergillosis ('starburst') and mucormycosis (closely apposed bundles of hyphae). Host inflammatory cells were absent or few in number within these lesions. In Coccidioides lesions, host inflammation was sparse as well. Fungal amyloid was a prominent feature of all lesions along with abundant SAP bound to hyphae and spherules. Fungal amyloid and SAP perhaps contributed to persistence in caseous necrosis lesions. SAP also bound to Aspergillus and Mucorales amyloid in vitro. CONCLUSIONS: A biofilm including amyloid and SAP is present in invasive fungal infections. This biofilm may dampen host defence leading to the characteristic sparse inflammatory reaction found in these infections. PMID- 26366293 TI - One-Year Results of Simultaneous Topography-Guided Photorefractive Keratectomy and Corneal Collagen Cross-Linking in Keratoconus Utilizing a Modern Ablation Software. AB - Purpose. To evaluate effectiveness of simultaneous topography-guided photorefractive keratectomy and corneal collagen cross-linking in mild and moderate keratoconus. Methods. Prospective nonrandomized interventional study including 20 eyes of 14 patients with grade 1-2 keratoconus that underwent topography-guided PRK using a Custom Ablation Transition Zone (CATz) profile with 0.02% MMC application immediately followed by standard 3 mw/cm(2) UVA collagen cross-linking. Maximum ablation depth did not exceed 58 MUm. Follow-up period: 12 months. Results. Progressive statistically significant improvement of UCVA from 0.83 +/- 0.37 logMAR preoperative, reaching 0.25 +/- 0.26 logMAR at 12 months (P < 0.001). Preoperative BCVA (0.27 +/- 0.31 logMAR) showed a progressive improvement reaching 0.08 +/- 0.12 logMAR at 12 months (P = 0.02). Mean Kmax reduced from 48.9 +/- 2.8 to 45.4 +/- 3.1 D at 12 months (P < 0.001), mean Kmin reduced from 45.9 +/- 2.8 D to 44.1 +/- 3.2 D at 12 months (P < 0.003), mean keratometric asymmetry reduced from 3.01 +/- 2.03 D to 1.25 +/- 1.2 D at 12 months (P < 0.001). The safety index was 1.39 at 12 months and efficacy index 0.97 at 12 months. Conclusion. Combined topography-guided PRK and corneal collagen cross-linking are a safe and effective option in the management of mild and moderate keratoconus. Precis. To our knowledge, this is the first published study on the use of the CATz ablation system on the Nidek Quest excimer laser platform combined with conventional cross-linking in the management of mild keratoconus. PMID- 26366295 TI - Practice of Pain Management by Indian Healthcare Practitioners: Results of a Paper Based Questionnaire Survey. AB - Objective. Understanding factors while selecting an analgesic and its usage pattern by Indian healthcare practitioners (HCPs). Methods. Questionnaire-based survey was conducted among six healthcare specialties. Results. Total 448 HCPs participated. Patient's age (72.8%, 74.4%, 87.5%, and 78.9%) and duration of therapy (70.8%, 66.2%, 69.6%, and 73.6%) were main attributes for selecting an opioid according to general practitioners (GPs), dentists, consulting physicians (CPs), and surgeons, respectively. Patient's age was important factor while selecting NSAID according to 77.60%, 66.91%, and 84.20% of GPs, dentists, surgeons, respectively. For mild pain, paracetamol was the choice according to 77%, 78.57% and 74% of GPs, CPs, and surgeons, respectively. For moderate pain, 77%, 87.50%, 68%, and 80.30% of GPs, CPs, surgeons and orthopedicians, respectively, preferred the use of paracetamol + tramadol combination. For moderate pain, NSAID + paracetamol and paracetamol+diclofenac were used by 68.94% and 47.73% of orthopedicians, respectively. Lack of pain clinic (38.8%) in city was commonly cited reason for not referring patients to pain clinics. Conclusion. Patient's age, duration of therapy, comorbid conditions, frequency of dosing, and severity of pain are important parameters while selecting analgesics. Paracetamol and its combinations are commonly used for mild and moderate pain, respectively. Pain clinics currently have limited presence in India. PMID- 26366294 TI - The Influence of Urinary Concentrations of Organophosphate Metabolites on the Relationship between BMI and Cardiometabolic Health Risk. AB - The objective was to determine whether detectable levels of OP metabolites influence the relationship between BMI and cardiometabolic health. This cross sectional study was conducted using 2227 adults from the 1999-2008 NHANES datasets. Urinary concentrations of six dialkyl phosphate metabolites were dichotomized to above and below the detection limit. Weighted multiple regression analysis was performed adjusting for confounding variables. Independent of BMI, individuals with detectable metabolites had higher diastolic blood pressure (for dimethylphosphate, diethylphosphate, and diethyldithiophosphate; P < 0.05), lower HDL (for diethyldithiophosphate; P = 0.02), and higher triglyceride (for dimethyldithiophosphate; P = 0.05) than those below detection. Contrarily, those with detectable dimethylthiophosphate had better LDL, HDL, and total cholesterol, independent of BMI. Individuals at a higher BMI range who had detectable diethylphosphate (interaction: P = 0.03) and diethylthiophosphate (interaction: P = 0.02) exhibited lower HDL, while little difference existed between OP metabolite detection statuses at lower BMIs. Similarly, individuals with high BMIs and detectable diethylphosphate had higher triglyceride than those without detectable levels, while minimal differences between diethylphosphate detection statuses were observed at lower BMIs (interaction: P = 0.02). Thus, cardiometabolic health outcome differs depending on the specific OP metabolite being examined, with higher BMIs amplifying health risk. PMID- 26366296 TI - Effect of Cortical Bone Thickness on Detection of Intraosseous Lesions by Ultrasonography. AB - Background. Usefulness of ultrasound (US) in detection of intrabony lesions has been showed. A cortical bone perforation or a very thin and intact cortical bone is prerequisite for this purpose. Objective. The current in vitro study was aimed at measuring the cut-off thickness of the overlying cortical bone which allows ultrasonic assessment of bony defects. Materials and Methods. 20 bovine scapula blocks were obtained. Samples were numbered from 1 to 20. In each sample, 5 artificial lesions were made. The lesions were made in order to increase the overlying bone thickness, from 0.1 mm in the first sample to 2 mm in the last one (with 0.1 mm interval). After that, the samples underwent ultrasound examinations by two practicing radiologists. Results. All five lesions in samples numbered 1 to 11 were detected as hypoechoic area. Cortical bone thickness more than 1.1 mm resulted in a failure in the detection of central lesions. Conclusion. We can conclude that neither bony perforation nor very thin cortical bones are needed to consider US to be an effective imaging technique in the evaluation of bony lesion. PMID- 26366297 TI - A Study to Inform the Design of a National Multicentre Randomised Controlled Trial to Evaluate If Reducing Serum Phosphate to Normal Levels Improves Clinical Outcomes including Mortality, Cardiovascular Events, Bone Pain, or Fracture in Patients on Dialysis. AB - Background. Retrospective, observational studies link high phosphate with mortality in dialysis patients. This generates research hypotheses but does not establish "cause-and-effect." A large randomised controlled trial (RCT) of about 3000 patients randomised 50 : 50 to lower or higher phosphate ranges is required to answer the key question: does reducing phosphate levels improve clinical outcomes? Whether such a trial is technically possible is unknown; therefore, a study is necessary to inform the design and conduct of a future, definitive trial. Methodology. Dual centre prospective parallel group study: 100 dialysis patients randomized to lower (phosphate target 0.8 to 1.4 mmol/L) or higher range group (1.8 to 2.4 mmol/L). Non-calcium-containing phosphate binders and questionnaires will be used to achieve target phosphate. PRIMARY ENDPOINT: percentage successfully titrated to required range and percentage maintained in these groups over the maintenance period. Secondary endpoints: consent rate, drop out rates, and cardiovascular events. Discussion. This study will inform design of a large definitive trial of the effect of phosphate on mortality and cardiovascular events in dialysis patients. If phosphate lowering improves outcomes, we would be reassured of the validity of this clinical practice. If, on the other hand, there is no improvement, a reassessment of resource allocation to therapies proven to improve outcomes will result. Trial Registration Number. This trial is registered with ISRCTN registration number ISRCTN24741445. PMID- 26366298 TI - Morphological Retrospective Study of Peritoneal Biopsies from Patients with Encapsulating Peritoneal Sclerosis: Underestimated Role of Adipocytes as New Fibroblasts Lineage? AB - Background. Encapsulating peritoneal sclerosis (EPS) is a rare but serious complication of peritoneal dialysis (PD). Besides the endothelial-to-mesenchymal transition (EMT), recently peritoneal adipocytes emerged as a potential source of fibrosis. We performed immunohistochemistry to approach EMT and to localize peritoneal adipocytes in peritoneal biopsies from PD-related EPS patients. Material and Methods. We investigated tissue expression of podoplanin, cytokeratin AE1/AE3 (mesothelium), calretinin (adipocytes), alpha-smooth muscle actin [alpha-SMA] (mesenchymal cells), interstitial mononuclear cell inflammation, and neoangiogenesis (CD3, CD4, CD8, CD20, CD68, and CD31 immunostainings, resp.). Results. Three patients (1 man/2 women; 17, 64, and 39 years old, resp.) developed EPS after 21, 90, and 164 months of PD therapy. In patients with EPS, we observed (1) loss of AE1/AE3 cytokeratin+ mesothelial cells without any evidence of migration into the interstitium, (2) disappearance of adipose tissue, (3) diffuse infiltration of calretinin+ cells in the areas of submesothelial fibrosis with a huge number of alpha-SMA and calretinin+ fusiform cells, and (4) increased vascular density. Conclusion. We report that the involvement of EMT in peritoneal fibrosis is difficult to demonstrate and that the calretinin+ adipocytes might be an underestimated component and a new source of myofibroblasts in peritoneal remodeling during PD-related EPS. PMID- 26366299 TI - Genetic Risk Score Predicts Late-Life Cognitive Impairment. AB - Introduction. A family history of Alzheimer's disease is a significant risk factor for its onset, but the genetic risk associated with possessing multiple risk alleles is still poorly understood. Methods. In a sample of 95 older adults (Mean age = 75.1, 64.2% female), we constructed a genetic risk score based on the accumulation of risk alleles in BDNF, COMT, and APOE. A neuropsychological evaluation and consensus determined cognitive status (44 nonimpaired, 51 impaired). Logistic regression was performed to determine whether the genetic risk score predicted cognitive impairment above and beyond that associated with each gene. Results. An increased genetic risk score was associated with a nearly 4-fold increased risk of cognitive impairment (OR = 3.824, P = .013) when including the individual gene polymorphisms as covariates in the model. Discussion. A risk score combining multiple genetic influences may be more useful in predicting late-life cognitive impairment than individual polymorphisms. PMID- 26366301 TI - Reduction of Pain and Edema of the Legs by Walking Wearing Elastic Stockings. AB - Aim. The objective of the current study was to evaluate the reduction of edema and pain with the use of elastic stockings. Method. The effect of walking on a treadmill for 50 minutes in the evening wearing elastic compression stockings on pain and edema was evaluated in a prospective randomized crossover clinical trial. In Assessment 1, the legs of participants were measured by volumetry at 7:00 a.m. and they were asked to perform their normal daily activities and to return at 4:00 p.m. Forty-two legs of 21 female patients with ages of the participants ranged from 32 to 72 years with signs and symptoms of chronic venous disease. The sizes of the legs of all patients were evaluated by water displacement volumetry and a visual analog scale was used to assess pain. Results. After walking for 50 minutes on the treadmill, the volume reduced (paired t-test: p value < 0.03). In relation to pain, there was a reduction in pain after the treadmill session using the elastic stocking (Wilcoxon signed rank test: p value < 0.007). Conclusion. The reduction of edema and pain of the legs during the course of the day can be accomplished with the use of elastic stockings, as well as walking. PMID- 26366300 TI - Retromolar Canal Associated with Age, Side, Sex, Bifid Mandibular Canal, and Accessory Mental Foramen in Panoramic Radiographs of Brazilians. AB - Background. The retromolar canal (RMC) is an anatomical variation that can cause complications in dental procedures. Method. The RMC was evaluated according to age, sex, and presence of accessory mandibular canal and accessory mental foramen, on both sides in 500 panoramic radiographs, belonging to individuals at the age of 7 to 20 years. The associations of interest were studied through Fisher's Exact Test and Pearson's Chi-Square Test, and the correlation was studied through Pearson's Correlation Coefficient (r). The significance level used was 5%. Results. The RMC was observed in 44 radiographs (8.8%), and out of those 24 were females. There was no statistically significant association between the RMC and age (p > 0.05; Fisher's Exact Test), sex (p = 0.787; Pearson's Chi Square Test), amount of mandibular canals and mental foramina, on both sides (p > 0.05; Pearson's Chi-Square Test). There was a significant association between RMC and side, the higher frequency of the canal being on the right side (p < 0.05; Fisher's Exact Test). Conclusions. Despite the low occurrence of the RMC, its identification and the verification of its dimensions and path are relevant, mainly in cases when anesthetic and surgical procedures can present failures or difficulties. PMID- 26366302 TI - Prevalence of Virulence Factors and Drug Resistance in Clinical Isolates of Enterococci: A Study from North India. AB - Along with emergence of multidrug resistance, presence of several virulence factors in enterococci is an emerging concept. This study was undertaken to determine the prevalence of various virulence factors phenotypically and genotypically in enterococci and study their association with multidrug resistance. A total of 310 enterococcal isolates were studied, comprising 155 E. faecium and 155 E. faecalis. Antimicrobial susceptibility testing was done by disc diffusion and agar dilution method. Hemolysin, gelatinase, biofilm production, and haemagglutination were detected phenotypically and presence of virulence genes, namely, asa1, gelE, cylA, esp, and hyl, was detected by multiplex PCR. Of the total, 47.41% isolates were high level gentamicin resistant (HLGRE) and 7.09% were vancomycin resistant (VRE). All the virulence traits studied were found in varying proportions, with majority in E. faecalis (p > 0.05). Strong biofilm producers possessed either asa1 or gelE gene. gelE silent gene was detected in 41.37% (12/29). However, increase in resistance was associated with significant decrease in expression or acquisition of virulence genes. Further, acquisition of vancomycin resistance was the significant factor responsible for the loss of virulence traits. Though it is presumed that increased drug resistance correlates with increased virulence, acquisition of vancomycin resistance might be responsible for reduced expression of virulence traits to meet the "biological cost" relating to VRE. PMID- 26366303 TI - In Vitro Comparison of Dynesys, PEEK, and Titanium Constructs in the Lumbar Spine. AB - Introduction. Pedicle based posterior dynamic stabilization systems aim to stabilize the pathologic spine while also allowing sufficient motion to mitigate adjacent level effects. Two flexible constructs that have been proposed to act in such a manner, the Dynesys Dynamic Stabilization System and PEEK rod, have yet to be directly compared in vitro to a rigid Titanium rod. Methods. Human lumbar specimens were tested in flexion extension, lateral bending, and axial torsion to evaluate the following conditions at L4-L5: Intact, Dynesys, PEEK rod, Titanium rod, and Destabilized. Intervertebral range of motion, interpedicular travel, and interpedicular displacement metrics were evaluated from 3rd-cycle data using an optoelectric tracking system. Results. Statistically significant decreases in ROM compared to Intact and Destabilized conditions were detected for the instrumented conditions during flexion extension and lateral bending. AT ROM was significantly less than Destabilized but not the Intact condition. Similar trends were found for interpedicular displacement in all modes of loading; however, interpedicular travel trends were less consistent. More importantly, no metrics under any mode of loading revealed significant differences between Dynesys, PEEK, and Titanium. Conclusion. The results of this study support previous findings that Dynesys and PEEK constructs behave similarly to a Titanium rod in vitro. PMID- 26366305 TI - Effects of Exercise in Immersive Virtual Environments on Cortical Neural Oscillations and Mental State. AB - Virtual reality environments are increasingly being used to encourage individuals to exercise more regularly, including as part of treatment those with mental health or neurological disorders. The success of virtual environments likely depends on whether a sense of presence can be established, where participants become fully immersed in the virtual environment. Exposure to virtual environments is associated with physiological responses, including cortical activation changes. Whether the addition of a real exercise within a virtual environment alters sense of presence perception, or the accompanying physiological changes, is not known. In a randomized and controlled study design, moderate-intensity Exercise (i.e., self-paced cycling) and No-Exercise (i.e., automatic propulsion) trials were performed within three levels of virtual environment exposure. Each trial was 5 minutes in duration and was followed by posttrial assessments of heart rate, perceived sense of presence, EEG, and mental state. Changes in psychological strain and physical state were generally mirrored by neural activation patterns. Furthermore, these changes indicated that exercise augments the demands of virtual environment exposures and this likely contributed to an enhanced sense of presence. PMID- 26366306 TI - Anesthetic Approach for a Patient with Jeune Syndrome. AB - Jeune syndrome (JS) is an autosomal recessive disease also known as asphyxiating thoracic dystrophy. A narrow bell-shaped thoracic wall and short extremities are the most typical features of the syndrome. Prognosis in JS depends on the severity of the pulmonary hypoplasia caused by the chest wall deformity. Most patient deaths are due to respiratory problems at early ages. Herein, we report a case of JS patient, who was scheduled for femoral extension under general anesthesia. The severity of respiratory problems in JS patients is thought to diminish with age. Our case supported this theory, and we managed the anesthetic process uneventfully. PMID- 26366307 TI - Takotsubo Cardiomyopathy in the Setting of Tension Pneumothorax. AB - Background. Takotsubo cardiomyopathy is defined as a transient left ventricular dysfunction, usually accompanied by electrocardiographic changes. The literature documents only two other cases of Takotsubo cardiomyopathy in the latter setting. Methods. A 78-year-old female presented to the ED with severe shortness of breath, hypertension, and tachycardia. On physical exam, heart sounds (S1 and S2) were regular and wheezing was noticed bilaterally. We found laboratory results with a WBC of 20.0 (103/MUL), troponin of 16.52 ng/mL, CK-mb of 70.6%, and BNP of 177 pg/mL. The patient was intubated for acute hypoxemic respiratory failure. A chest X-ray revealed a large left-sided tension pneumothorax. Initial echocardiogram showed apical ballooning with a LVEF of 10-15%. A cardiac angiography revealed normal coronary arteries with no coronary disease. After supportive treatment, the patient's condition improved with a subsequent echocardiogram showing a LVEF of 60%. Conclusion. The patient was found to have Takotsubo cardiomyopathy in the setting of a tension pneumothorax. The exact mechanisms of ventricular dysfunction have not been clarified. However, multivessel coronary spasm or catecholamine cardiotoxicity has been suggested to have a causative role. We suggest that, in our patient, left ventricular dysfunction was induced by the latter mechanism related to the stress associated with acute pneumothorax. PMID- 26366304 TI - Neural Plasticity in Common Forms of Chronic Headaches. AB - Headaches are universal experiences and among the most common disorders. While headache may be physiological in the acute setting, it can become a pathological and persistent condition. The mechanisms underlying the transition from episodic to chronic pain have been the subject of intense study. Using physiological and imaging methods, researchers have identified a number of different forms of neural plasticity associated with migraine and other headaches, including peripheral and central sensitization, and alterations in the endogenous mechanisms of pain modulation. While these changes have been proposed to contribute to headache and pain chronification, some findings are likely the results of repetitive noxious stimulation, such as atrophy of brain areas involved in pain perception and modulation. In this review, we provide a narrative overview of recent advances on the neuroimaging, electrophysiological and genetic aspects of neural plasticity associated with the most common forms of chronic headaches, including migraine, cluster headache, tension-type headache, and medication overuse headache. PMID- 26366309 TI - Upper Gastrointestinal Bleeding from Gastric Amyloidosis in a Patient with Smoldering Multiple Myeloma. AB - Amyloidosis is a common complication of patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), and multiple myeloma (MM). This proteinaceous material can be deposited intercellularly in any organ system, including the gastrointestinal (GI) tract. In the GI tract, amyloidosis affects the duodenum most commonly, followed by the stomach and colorectum. Gastric amyloidosis causes symptoms of nausea, vomiting, early satiety, abdominal pain, and GI bleeding. A case of upper GI bleeding from gastric amyloidosis is presented in a patient with SMM. Esophagogastroduodenoscopy (EGD) revealed a gastric mass. Endoscopic biopsies revealed amyloid deposition in the lamina propria, consistent with gastric amyloidosis. Liquid chromatography tandem mass spectrometry performed on peptides extracted from Congo red-positive microdissected areas of paraffin-embedded stomach specimens revealed a peptide profile consistent with AL- (lambda-) type amyloidosis. Based on this and multiple other case reports, we recommend that patients with GI bleeding and MGUS, SMM, or MM undergo EGD and pathologic examination of endoscopic biopsies of identified lesions using Congo red stains for amyloidosis for early diagnosis and treatment. PMID- 26366308 TI - Chylous Ascites: A Rare Adverse Effect of Methimazole Treatment for Grave's Disease-A Case Report and Review of the Literature. AB - A 40-year-old woman was admitted due to an urticarial rash that was attributed to recent onset of methimazole treatment for a diagnosis of Grave's disease. The patient had no prior significant medical history and used no medications, including over-the-counter or herbal medications. Her sister had Grave's disease. On admission, the patient received corticosteroids with improvement in her rash. On the second day of the hospitalization, the patient complained of abdominal discomfort. Abdominal ultrasound revealed a large amount of new onset ascites. Peritoneal tap yielded a milky fluid with high triglyceride level (12.2 mmol/L or 1080 mg/dL), consistent with chylous ascites. After discontinuation of the methimazole, the ascites disappeared. The patient later underwent therapeutic thyroidectomy, after which all features of thyrotoxicosis had improved. PMID- 26366310 TI - High-Grade Leiomyosarcoma Arising in a Previously Replanted Limb. AB - Sarcoma development has been associated with genetics, irradiation, viral infections, and immunodeficiency. Reports of sarcomas arising in the setting of prior trauma, as in burn scars or fracture sites, are rare. We report a case of a leiomyosarcoma arising in an arm that had previously been replanted at the level of the elbow joint following traumatic amputation when the patient was eight years old. He presented twenty-four years later with a 10.8 cm mass in the replanted arm located on the volar forearm. The tumor was completely resected and pathology examination showed a high-grade, subfascial spindle cell sarcoma diagnosed as a grade 3 leiomyosarcoma with stage pT2bNxMx. The patient underwent treatment with brachytherapy, reconstruction with a free flap, and subsequently chemotherapy. To the best of our knowledge, this is the first case report of leiomyosarcoma developing in a replanted extremity. Development of leiomyosarcoma in this case could be related to revascularization, scar formation, or chronic injury after replantation. The patient remains healthy without signs of recurrence at three-year follow-up. PMID- 26366312 TI - Sub-Tenon Injections of Triamcinolone Acetonide Had Limited Effect on Cystoid Macular Edema Secondary to Nanoparticle Albumin-Bound-Paclitaxel (Abraxane). AB - Purpose. To report the first case of cystoid macular edema (CME) induced by nanoparticle albumin-bound- (nab-) paclitaxel treated with sub-Tenon injections of triamcinolone acetonide (STTA) with detailed long-term follow-up. Case. A 39 year-old Japanese woman with breast cancer presents with decreased vision in both eyes while receiving nab-paclitaxel. Two STTA treatments were administered for persistent CME in her right eye. Central retinal thickness (CRT) of the treated eye decreased after the first STTA, but there was no change after the second STTA. CRT of the other eye and bilateral visual acuity (VA) showed no change after each treatment. However, this patient experienced gradual recovery of visual function after nab-paclitaxel treatment was completed, 3 months after the second STTA. Improvements in VA and CRT did not overlap in time. Moreover, there was a big improvement time lag in VA between the eyes. Conclusion. Cessation of nab-paclitaxel could lead to resolution of CME more than STTA, although STTA had some effect. Since nab-paclitaxel has been recently approved for treating more types of malignancies, the number of the patients with this CME is expected to increase in the near future. Patients and physicians should understand this side effect and prepare for other treatment options. PMID- 26366311 TI - Progression of an Invasive ACTH Pituitary Macroadenoma with Cushing's Disease to Pituitary Carcinoma. AB - Pituitary carcinomas are very rare tumors that in most cases produce prolactin and adrenocorticotropic hormone (ACTH). It is a challenge to diagnosis of a pituitary carcinoma before disclosed symptomatic metastasis. We report the case of a female patient with Cushing's disease who underwent three transsphenoidal surgeries, with pathological findings of common ACTH pituitary adenoma including Ki-67 expression <3%. She achieved hypocortisolism after the 3rd surgery although ACTH levels remained slightly elevated. The patient returned some time later with fast worsening of hypercortisolism. Magnetic resonance imaging showed clivus invasion, which led to a fourth surgery and radiation. This time, immunohistochemistry revealed strong Ki-67 (10% to 15%) and p53 expression. Liver and lumbar spine metastases were found on workup. The patient died after few months due to lung infection. Pituitary carcinomas are rare, and the transformation of an ACTH-secreting pituitary adenoma into a carcinoma is exceptional. The difficulty of defining markers for the diagnosis of carcinoma, before metastasis diagnosis, in order to change the management of the disease, is a challenge. PMID- 26366313 TI - Congenital Upper Eyelid Coloboma: Clinical and Surgical Management. AB - Purpose. The goal was to describe our experience in the surgical management and treatment of four patients with congenital upper eyelid colobomas. Methods. A descriptive, observational, retrospective study was performed including patients with congenital eyelid colobomas referred to Asociacion para Evitar la Ceguera en Mexico I.A.P. "Dr. Luis Sanchez Bulnes" between 2004 and 2014 and assessed by the Oculoplastics and Orbit Service. Results. The four cases required surgical treatment of the eyelid defects before one year of age and their evolution was monitored from the time of referral to the present day. One of the patients needed a second surgical procedure to repair the eyelid defect and correct the strabismus. Conclusions. Eyelid colobomas are a potential threat to vision at an early age, which requires close monitoring of the visual development of patients. PMID- 26366314 TI - Simultaneous Bilateral Rupture of the Triceps Tendon in a Renal Transplant Patient. AB - The unilateral rupture of the triceps brachii tendon is a rare lesion representing 1% of all tendon injuries. The most common causes are the result of a contraction against resistance (especially weightlifters) and direct trauma. It has also been associated with systemic diseases such as diabetes mellitus, chronic renal failure, secondary hyperparathyroidism, and use of systemic corticosteroids. Simultaneous bilateral rupture of the triceps tendons is less frequent and has been described in association with chronic metabolic disorders, especially in those patients on hemodialysis. This paper presents a case of bilateral triceps tendon rupture of a 36-year-old woman with renal transplantation secondary to chronic renal failure. Early surgical repair was performed using a bone tunnel technique with a nonabsorbable suture. Clinically active extension with 135 degrees of range of motion was achieved. PMID- 26366315 TI - A Rare Cause of Prepubertal Gynecomastia: Sertoli Cell Tumor. AB - Prepubertal gynecomastia due to testis tumors is a very rare condition. Nearly 5% of the patients with testicular mass present with gynecomastia. Sertoli cell tumors are sporadic in 60% of the reported cases, while the remaining is a component of multiple neoplasia syndromes such as Peutz-Jeghers syndrome and Carney complex. We present a 4-year-old boy with gynecomastia due to Sertoli cell tumor with no evidence of Peutz-Jeghers syndrome or Carney complex. PMID- 26366316 TI - Metastatic Squamous Cell Carcinoma Component from an Adenosquamous Carcinoma of the Lung with Identical Epidermal Growth Factor Receptor Mutations. AB - The case reported is a young "light" ex-smoker who initially had a localized adenosquamous carcinoma bearing an epidermal growth factor receptor (EGFR) sensitizing mutation. He first recurred six months after initial treatment within the brain with a pure squamous histology and the same EGFR mutation. Surgical resection and radiation rendered him disease-free. Subsequent isolated recurrence within the lung eighteen months later was a pure adenocarcinoma, again with the same identified EGFR mutation. These histologic changes (from adenosquamous to pure squamous to pure adenocarcinoma) have been described but not before in the absence of any selection pressure with EGFR tyrosine kinase inhibitors. This case points out the histologic "flexibility" of EGFR mutant lung cancers and the importance for appropriate molecular testing in nonsmokers with lung cancer of any histologic type. PMID- 26366317 TI - A Case of Systemic Lupus Erythematosus Presenting as Guillain-Barre Syndrome. AB - Systemic lupus erythematosus (SLE) is an autoimmune systemic disease with multiple organ involvement with high morbidity and mortality rate. Among the severe potential fatal complications are those of the central and peripheral nervous system which usually develop during the course of the disease and very rarely from the outset of the disease. We are reporting a rare case of Miller Fisher (MFS) variant of Guillain-Barre syndrome (GBS) as the first manifestation of SLE in a 41-year-old female who progressed to flaccid paralysis with no neurological improvement with initial immunosuppressive therapy, plasmapheresis, and first cycle of intravenous immunoglobulin (IVIG) but with remarkable and complete recovery after the second 5-day course of IVIG. PMID- 26366318 TI - Smoking Status Effect on Inflammatory Markers in a Randomized Trial of Current and Former Heavy Smokers. AB - Background. The level of systemic inflammation as measured by circulating levels of C-reactive protein (CRP) and interleukin-6 (IL-6) is linked to an increased risk for cardiovascular diseases (CVD) and cancer. Methods. We recruited 154 current and former smokers between 40 and 80 years of age with 25 or more pack years of smoking history to study the relationship between inflammatory markers (CRP and IL-6) and smoking status. Results. Our results show that male smokers had significantly higher levels of serum IL-6 compared to male former smokers. We did not find any gender specific differences for smoking and CRP levels but the IL-6 levels were slightly lower in females compared to males. Additionally, our results show that CRP is significantly associated with IL-6 regardless of smoking status. Modelling indicates that the significant predictors of CRP levels were biomarkers of the metabolic syndrome while the significant predictors of IL-6 levels were age and plasma triglycerides among former smokers and the numbers of smoked packs of cigarettes per year among smokers. Conclusions. In conclusion, our study showed that CRP levels were not associated with markers of smoking intensity. However, IL-6 levels were significantly associated with smoking especially among current smokers. PMID- 26366319 TI - Sustained Release Formulation of Primaquine for Prevention of Relapse of Plasmodium vivax Malaria: A Randomized, Double-Blind, Comparative, Multicentric Study. AB - Background. Primaquine is used to eradicate latent Plasmodium vivax parasite from liver, with administration of standard dose daily up to 14 days. We studied efficacy, safety, and tolerability of sustained release (SR) formulation of primaquine in comparison with conventional primaquine in preventing relapse of P. vivax malaria. Methods. Microscopically confirmed cases of P. vivax malaria received chloroquine therapy for three days. Aparasitemic and asymptomatic patients were then randomized to receive either conventional primaquine 15 mg for 14 days or primaquine SR 15 mg for 14 days, or primaquine SR 30 mg for seven days. Results. Of the 360 patients, who received chloroquine therapy, 358 patients were randomized. Two-hundred eighty-eight patients completed six-month follow-up and four patients (three: conventional primaquine 15 mg (2.86%), one: primaquine SR 30 mg (0.93%)) showed relapse confirmed by PCR genotyping. Drug compliance was significantly better in primaquine SR 30 mg group (95.57%, p = 0.039) without any serious adverse events. Conclusion. Primaquine SR 15 mg and primaquine SR 30 mg could be an effective alternative to conventional primaquine 15 mg due to their comparable cure rates and safety profile. Shorter treatment duration with primaquine SR 30 mg may increase patient compliance and may further reduce relapse rates. Clinical Trial Registration. This trial is registered with CTRI/2010/091/000245. PMID- 26366320 TI - Social Reactions, Self-Blame and Problem Drinking in Adult Sexual Assault Survivors. AB - OBJECTIVE: The purpose of this study was to test a model of the relations of social reactions to sexual assault disclosure, self-blame and problem drinking. This is the first study to investigate whether type of self-blame has different relationships with social reactions and problem drinking in a large, diverse sample of sexually assaulted women. These relationships are important to investigate in order to identify specific targets for treatment and intervention with sexual assault victims and their social networks. METHOD: Community-residing female sexual assault survivors (N = 1863) in a large metropolitan area completed a mail survey about sexual assault, social reactions to disclosure, self-blame attributions, and problem drinking symptoms. RESULTS: Structural equation modeling showed that characterological self-blame mediated the effect of negative social reactions on drinking, but behavioral self-blame did not function as a mediator. A second model showed unique relationships of specific positive and negative social reactions to drinking through characterological and behavioral self-blame. CONCLUSIONS: Characterological self-blame needs to be targeted in treatment and intervention with survivors, as it appears to be a key mechanism through which social reactions may influence recovery. Secondary prevention with informal social networks should educate people about social reactions to avoid negative reactions and promote those that are helpful, so people can better respond to survivors' sexual assault disclosures and improve recovery. PMID- 26366321 TI - Measuring Sexual Aggression Perpetration in College Men: A Comparison of Two Measures. AB - OBJECTIVE: The present study was designed to provide a comparison of rates of self-reported sexual aggression perpetration obtained using two different measures - a version of the Sexual Experiences Survey (SES; Abbey et al, 2007; Koss, Gidycz, & Wisniewski, 1987) and the Sexual Strategies Scale (SSS, Strang, et al, 2013; Struckman-Johnson, Struckman-Johnson, & Anderson, 2003). We also examined the psychometric structure of each measure using Rasch model item analysis (Rasch, 1966). METHOD: Two equivalent cohorts of entering freshman males (N = 994 and N = 1043) from a large northeastern university completed online measures at the end of their first semester. RESULTS: Identical proportions of men reported using intoxication strategies (3%) and physical force (1%) during the past semester on both measures. However, more men reported verbal strategies on the SSS (7.8%) compared with the SES (3.7%), even when restricting to equivalent items. Rasch analysis suggested that the SSS conformed better to a unidimensional continuum of perpetration severity than the SES; however, Rasch analysis did not provide definitive support for either a tactic - based (SSS) nor a tactic plus outcome- based (SES) hierarchy. CONCLUSIONS: Both measures functioned adequately. However, the SSS may be preferred for its better Rasch properties, better assessment of the less severe tactics, and simpler wording. PMID- 26366322 TI - Rising Syphilis Infection among Rural HIV-Infected Men who Routinely Received Risk-Reduction Counseling: New Challenges to HIV Prevention in Clinical Care. AB - OBJECTIVE: Syphilis incidence has been steadily increasing among HIV-infected men in the United States, representing an important public health challenge to HIV prevention. Clinic-based HIV prevention interventions are available but may need to be revisited in response to syphilis epidemic. We wanted to better understand the current epidemiology of syphilis in rural HIV-infected men who routinely received HIV risk-reduction counseling in order to plan more effective HIV prevention strategies in clinical care. METHODS: We conducted a retrospective cohort study to examine factors associated with syphilis infections in rural HIV infected men who received sexually transmitted disease screening and HIV risk reduction counseling during HIV primary care from January 2008 to June 2013. We assessed patients' demographic, clinical, behavioral and psychosocial characteristics and performed a multivariable exact logistic regression to identify factors related to syphilis. RESULTS: Despite routine risk screening and HIV risk-reduction counseling, a total of 51 syphilis infections were diagnosed among 702 HIV-infected men (5 patients were diagnosed >= 2 episodes). The majority of the study participants was sexually active and reported at least one unsafe sexual behavior, mainly inconsistent condom use. Younger age (<35 years, adjusted odds ratio (aOR)=3.09), higher educational attainment (some college or above, aOR=3.72), and perception that the partner may have sex with other people (aOR=3.10) were significantly associated with syphilis infection. Non-injection drug use was related to syphilis in HIV-infected men who have sex with men (aOR=2.86). DISCUSSION: Some HIV-infected men, especially young, educated men, or those who perceived that their partners may have sex with other people, continue to have high-risk behaviors that increase their own risks of acquiring syphilis and may also facilitate HIV transmission. New strategies need to be developed for HIV primary care providers to help HIV-infected patients maintain safer sex practices. PMID- 26366323 TI - Stuck between a rock and a hard place: The relationship between Latino/a's personal connections to immigrants and issue salience and presidential approval. AB - The Obama administration has simultaneously marketed the prospect of providing undocumented immigrants a pathway to citizenship through comprehensive immigration reform and overseen mass deportations of mostly Latino immigrants. While it is clear that immigration policy was highly influential to Latino voters in 2012, it remains unclear how this political hypocrisy is being interpreted by Latino voters. As deportations have risen steadily during the Obama administration, there has been little research on how deportations and personal connections to undocumented immigrants have influenced the political attitudes of the Latino/a electorate. Using a nationally representative survey of 800 registered Latino/a voters administered in 2013, we explore the relationships between personal connections to undocumented immigrants and issue salience among Latinos as well as Latinos' views of President Obama. This study finds that registered Latino voters who know deportees and undocumented immigrants are more likely to report that they think the President and Congress should act on immigration policy versus all other policies. Moreover, Latino voters who know someone who is undocumented are less likely to have favorable views towards President Obama. This study has implications for our collective knowledge of how direct and indirect connections to policy outcomes influences the political behavior of the highly influential Latino/a electorate and how political and policy outcomes will be influenced in the future when a much higher proportion of the electorate have such connections. PMID- 26366324 TI - Analysis of Landslides Triggered by October 2005, Kashmir Earthquake. AB - INTRODUCTION: The October 2005, Kashmir earthquake main event was triggered along the Balakot-Bagh Fault which runs from Bagh to Balakot, and caused more damages in and around these areas. Major landslides were activated during and after the earthquake inflicting large damages in the area, both in terms of infrastructure and casualties. These landslides were mainly attributed to the minimum threshold of the earthquake, geology of the area, climatologic and geomorphologic conditions, mudflows, widening of the roads without stability assessment, and heavy rainfall after the earthquake. These landslides were mainly rock and debris falls. Hattian Bala rock avalanche was largest landslide associated with the earthquake which completely destroyed a village and blocked the valley creating a lake. DISCUSSION: The present study shows that the fault rupture and fault geometry have direct influence on the distribution of landslides and that along the rupture zone a high frequency band of landslides was triggered. There was an increase in number of landslides due to 2005 earthquake and its aftershocks and that most of earthquakes have occurred along faults, rivers and roads. It is observed that the stability of landslide mass is greatly influenced by amplitude, frequency and duration of earthquake induced ground motion. Most of the slope failures along the roads resulted from the alteration of these slopes during widening of the roads, and seepages during the rainy season immediately after the earthquake. CONCLUSION: Landslides occurred mostly along weakly cemented and indurated rocks, colluvial sand and cemented soils. It is also worth noting that fissures and ground crack which were induced by main and after shock are still present and they pose a major potential threat for future landslides in case of another earthquake activity or under extreme weather conditions. PMID- 26366325 TI - Consistency between beliefs and behavior regarding use of substances in recovery. AB - This paper addresses the assumption that pathways to recovery from substance abuse and dependence, and the language used to define one's relationship to substances, translate to actual beliefs and behaviors in terms of substance use. We draw on social representation theory, and use data from a large web-based study (n=9,341) whose goal was to understand how individuals in recovery define what recovery means to them. We often hear people say that they are "in recovery," and present findings now provide empirical evidence of the prevalent meanings of this ubiquitous expression. The belief that recovery is abstinence was broadly held in our sample, especially among those exposed to treatment and 12-step self-help groups and who define themselves as in recovery-and most (but not all) of such individuals are complete abstainers (no alcohol or drugs). In contrast, among the "self-changers" who did not attend treatment or self-help groups, the most common self-definition was used to have an alcohol or drug problem but don't any more, half of whom believe that recovery is abstinence while half do not, and only one-third are abstainers. Findings are of public health relevance, as it is estimated that among American adults alone, 10% report having had alcohol or drug problems but no longer do (The New York State Office of Alcoholism and Substance Abuse Services (OASAS), 2012). In line with the central concepts of social representation theory, people's pathways to recovery have a strong effect on how they define themselves and their behaviors and beliefs, but it is not universal. PMID- 26366326 TI - The expanding world of hybrid perovskites: materials properties and emerging applications. PMID- 26366327 TI - Inositol Analysis by HPLC and Its Stability in Scavenged Sample Conditions. AB - Inositol is a 6-carbon sugar alcohol that has been shown in limited studies to reduce retinopathy of prematurity and chronic lung disease in premature newborns. Developmentally it has a high concentration in the fetus that decreases with gestational age. It is transported from the fetus to the mother across the placenta. Although studies are underway to determine inositol kinetics in premature newborns treated therapeutically, the effects of gestational age, age after birth, and feeding on inositol concentrations after birth have not been studied adequately in premature newborns. Such studies would minimize blood removal and trauma in preterm newborns by using plasma samples scavenged from the clinical laboratory to measure inositol after birth, if they remain stable. This report describes a new high pressure liquid chromatographic assay for inositol and its use to study the stability of inositol in conditions of storage that might be encountered within the clinical laboratory. The assay is linear from 0 to 1000 Mm with a lower limit of quantitation of 50 MUM. Inositol in human plasma remains stable in refrigeration and at room temperature for up to 14 days and is not affected by storage in red blood cells that are intact or lysed. Anticoagulants encountered in clinical blood samples do not interfere with the chromatograms. Thus, it is feasible to measure the changes in inositol concentrations in plasma from preterm newborns that is scavenged from the clinical laboratory after storage for as long as 14 days. PMID- 26366328 TI - Pretraumatic Stress Reactions in Soldiers Deployed to Afghanistan. AB - Posttraumatic Stress Disorder is a diagnosis related to the past. Pre-traumatic stress reactions, as measured by intrusive involuntary images of possible future stressful events and their associated avoidance and increased arousal, have been overlooked in the PTSD literature. Here we introduce a scale that measures pre traumatic stress reactions providing a clear future-oriented parallel to the posttraumatic stress reactions described in the diagnostic criteria for PTSD. We apply this pre-traumatic stress reactions checklist (PreCL) to Danish soldiers before, during, and after deployment to Afghanistan. The PreCL has good internal consistency and is highly correlated with a standard measure of PTSD symptoms. The PreCL as answered before the soldiers' deployment significantly predicted level of PTSD symptoms during and after their deployment, while controlling for baseline PTSD symptoms and combat exposure measured during and after deployment. The findings have implications for the conceptualization of PTSD, screening, and treatment. PMID- 26366329 TI - Neighborhood Poverty, College Attendance, and Diverging Profiles of Substance Use and Allostatic Load in Rural African American Youth. AB - A subset of African American youth who live in impoverished neighborhoods display resilient profiles academically and behaviorally. We hypothesized that this resilience might be "skin-deep," in that the ongoing efforts needed to achieve success might take a physiological toll on these youth. At age 19, 452 rural African American youth were assessed on broader contextual risk (neighborhood poverty) and external indicators of success (college attendance). One year later, participants were assessed on substance use and cumulative physiological risk (allostatic load). African American youth from more disadvantaged neighborhoods who attended college had lower levels of substance use, but higher levels of allostatic load compared to those from less disadvantaged neighborhoods who attended college, or to those who did not attend college. These findings indicate that a subset of African American youth from poor neighborhoods exhibits a profile of "skin-deep resilience," characterized by external successes combined with heightened internal physiological risk. PMID- 26366331 TI - Advancing pediatric psychiatry research: linking neurobiological processes to novel treatment and diagnosis through Research Domain Criteria (RDoC). PMID- 26366330 TI - ADHD & Pharmacotherapy: Past, Present and Future: A Review of the Changing Landscape of Drug Therapy for Attention Deficit Hyperactivity Disorder. AB - Attention deficit hyperactivity disorder (ADHD) is the most common neurobiological disorder in children, with a prevalence of ~6-7%1,2 that has remained stable for decades2. The social and economic burden associated with patients3, families, and broader systems (healthcare/educational) is substantial, with the annual economic impact of ADHD exceed $30 billion in the US alone4. Efficacy of pharmacotherapy in treating ADHD symptoms has generally been considerable with at least 3/4 of individuals benefitting from pharmacotherapy, typically in the form of stimulants5. In this review, we begin by briefly reviewing the history of pharmacotherapy in relation to ADHD, before focusing (primarily) on the state-of-the-field on themes such as biophysiology, pharmacokinetics, and pharmacogenomics. We conclude with a summary of emerging clinical and research studies, particularly the potential role for precision therapy in matching ADHD patients and drug types. PMID- 26366332 TI - Regulatory and funding strategies to develop a safety study of an auditory brainstem implant in young children who are deaf. PMID- 26366333 TI - Valproic Acid-Induced Severe Acute Pancreatitis with Pseudocyst Formation: Report of a Case. AB - Valproic acid is the most widely used anti-epilep-tic drug in children, and it is probably the most frequent cause of drug-induced acute pancreatitis. Outcomes for patients with valproic acid-associated pancreatitis vary from full recovery after discontinuation of the drug to severe acute pancreatitis and death. Here, we present a case of valproic acid-induced severe acute pancreatitis with pseudocyst formation in a 10-year-old girl with cerebral palsy and generalized tonic-clonic seizure. There was no resolution of the pseudocyst after discontinuation of valproic acid. The patient became symptomatic with a progressive increase in the size of the pseudocyst. She was successfully treated with cystogastrostomy and was well at 12-month follow-up. PMID- 26366334 TI - Keeping Nanoparticles Fully Functional: Long-Term Storage and Alteration of Magnetite. AB - Magnetite is an iron oxide found in rocks. Its magnetic properties are used for paleoclimatic reconstructions. It can also be synthesized in the laboratory to exploit its magnetic properties for bio- and nanotechnological applications. However, although the magnetic properties depend on particle size in a well understood manner, they also depend on the structure of the oxide, because magnetite oxidizes to maghemite under environmental conditions. The dynamics of this process have not been well described. Here, a study of the alteration of magnetite particles of different sizes as a function of their storage conditions is presented. Smaller nanoparticles are shown to oxidize more rapidly than larger ones, and that the lower the storage temperature, the lower the measured oxidation. In addition, the magnetic properties of the altered particles are not decreased dramatically, thus suggesting that this alteration will not impact the use of such nanoparticles as medical carriers. PMID- 26366335 TI - Flexible Distributed Bragg Reflectors from Nanocolumnar Templates. PMID- 26366336 TI - Developmental Programming: Priming Disease Susceptibility for Subsequent Generations. AB - Racial and/or ethnic minorities carry the highest burden of many adverse health outcomes intergenerationally We propose a paradigm in which developmental programming exacerbates the effects of racial patterning of adverse environmental conditions, thereby contributing to health disparity persistence. Evidence that developmental programming induces a heightened response to adverse exposures ("second hits") encountered later in life is considered. We evaluated the evidence for the second hit phenomenon reported in animal and human studies from three domains (air, stress, nutrition). Original research including a gestational exposure and a childhood or adulthood second hit exposure was reviewed. Evidence from animal studies suggest that prenatal exposure to air pollutants is associated with an exaggerated reaction to postnatal air pollution exposure, which results in worse health outcomes. It also indicates offspring exposed to prenatal maternal stress produce an exaggerated response to subsequent stressors, including anxiety and hyper-responsiveness of the hypothalamic-pituitary-adrenal axis. Similarly, prenatal and postnatal Western-style diets induce synergistic effects on weight gain, metabolic dysfunction, and atherosclerotic risk. Cross domain second hits (e.g., gestational air pollution followed by childhood stressor) were also considered. Suboptimal gestational environments induce exaggerated offspring responses to subsequent environmental and social exposures. These developmental programming effects may result in enhanced sensitivity of ongoing, racially patterned, adverse exposures in race/ethnic minorities, thereby exacerbating health disparities from one generation to the next. Empirical assessment of the hypothesized role of priming processes in the propagation of health disparities is needed. Future social epidemiology research must explicitly consider synergistic relationships among social environmental conditions to which gestating females are exposed and offspring exposures when assessing causes for persistent health disparities. PMID- 26366339 TI - How case reports have contributed to the progress of surgery. PMID- 26366338 TI - Regulation of miRNAs by agents targeting the tumor stem cell markers DCLK1, MSI1, LGR5, and BMI1. AB - Gastrointestinal cancers such as colorectal, pancreatic, liver, gastric, and esophageal, are the most common forms of malignant cancers. MicroRNAs (miRNA) play important role in regulating gastrointestinal cancer progress either as potent oncogenes or tumor suppressors. In this report, we will discuss the importance of several tumor suppressors involved in colon or pancreatic cancer. Some recent studies on tumor stem cells and regulation of these miRNAs via agents targeting the tumor stem cell markers doublecortin-like kinase 1 (DCLK1), Musashi 1 (MSI1), polycomb protein BMI1, and WNT genes (LGR5 and ASCL2) will also be discussed. Agents such as siRNA/shRNA, small molecule kinase inhibitors, and general herbal drugs (curcumin) targeting these tumor stem cell markers and tumor suppressor miRNAs could be the perfect therapeutic agents for the treatment of these cancers. PMID- 26366337 TI - Protective and Pathogenic Responses to Chikungunya Virus Infection. AB - Chikungunya virus (CHIKV) is an arbovirus responsible for causing epidemic outbreaks of human disease characterized by painful and often debilitating arthralgia. Recently CHIKV has moved into the Caribbean and the Americas resulting in massive outbreaks in naive human populations. Given the importance of CHIKV as an emerging disease, a significant amount of effort has gone into interpreting the virus-host interactions that contribute to protection or virus induced pathology following CHIKV infection, with the long term goal of using this information to develop new therapies or safe and effective anti-CHIKV vaccines. This work has made it clear that numerous distinct host responses are involved in the response to CHIKV infection, where some aspects of the host innate and adaptive immune response protect from or limit virus-induced disease, while other pathways actually exacerbate the virus-induced disease process. This review will discuss mechanisms that have been identified as playing a role in the host response to CHIKV infection and illustrate the importance of carefully evaluating these responses to determine whether they play a protective or pathologic role during CHIKV infection. PMID- 26366340 TI - Solitary pleural metastasis from renal cell carcinoma: a case of successful resection. AB - While renal cell carcinoma frequently metastasizes to the lung, solitary pleural metastasis without lung involvement is extremely rare. A 69-year-old man was admitted to our hospital with a solitary pleural metastasis 6 years after surgery for renal cell carcinoma. Needle biopsy was performed, and the tumor was diagnosed as a metastasis of renal cell carcinoma. The pleural tumor was surgically resected. The patient received interferon-alpha as postoperative therapy. He has been alive for 9 years without recurrence. Only 11 cases of solitary pleural metastasis have been reported thus far, and of these, 7 involved a large amount of pleural effusion resulting in a poor prognosis. This is the first reported case of solitary pleural metastasis from renal cell carcinoma, which was curatively resected, as indicated by long-term survival. PMID- 26366341 TI - Late recurrence of a tumor of Ewing's sarcoma family of tumors: report of a case. AB - A 27-year-old female presented with a history of a right chest wall tumor at 3 years of age. At that time, the tumor was surgically resected and diagnosed as Ewing's sarcoma (EWS), and postoperative chemoradiotherapy was administered. The patient remained disease-free for 25 years. At age 27, chest computed tomography revealed a mass adjacent to the anterolateral thoracic wall. After surgery, the diagnosis was primitive neuroectodermal tumor (PNET). She died of the disease 10 months later. PNET and EWS were integrated into a single item in the 2002 WHO classification; thus, they are considered clinically and pathologically identical. The morphologic, immunohistochemical, and molecular biological characteristics of both specimens showed that the second tumor was a local recurrence of Ewing's sarcoma family of tumors (ESFT). Our case is the longest duration local recurrence reported. Long-term recurrences of ESFT and patients with recurrent ESFT have a poor prognosis; thus, long-term follow-up is necessary. PMID- 26366342 TI - Hepatic angiomyolipoma with special attention to radiologic imaging. AB - BACKGROUND: Angiomyolipoma is a unique mesenchymal neoplasm composed of blood vessels as well as smooth muscle and adipose cells. The liver is a less common site of origin, and hepatic angiomyolipoma is often an incidental finding on diagnostic imaging or is identified on evaluation of nonspecific symptoms. CASE PRESENTATION: We experienced four patients who were diagnosed histologically with hepatic angiomyolipoma. The preoperative diagnoses were angiomyolipoma in two patients, hepatocellular carcinoma in one, and cavernous hemangioma in one. Three patients were treated with hepatectomy (one laparoscopic and two open approaches), and the diagnosis was completed by histological investigation of the resected specimen. The remaining one was diagnosed from tumor needle biopsy. Diffusion-weighted magnetic resonance imaging (MRI) with respiratory triggering using b values of 0 and 800 s/mm(2) was employed. An apparent diffusion coefficient map was generated from b values of 0 and 800 s/mm(2) for calculation of the apparent diffusion coefficient. The apparent diffusion coefficient values were calculated as 3.66, 1.21, 1.80, and 0.91 in patients 1 to 4, respectively. In MRI imaging, fat component was clearly demonstrated with chemical shift imaging in three patients. Early venous return was detected in three patients with computed tomography angiography. CONCLUSION: Fat component and early venous return are important for a correct diagnosis of hepatic angiomyolipoma. Unfortunately, apparent diffusion coefficient values in hepatic angiomyolipoma were overlapping with those in other benign and malignant tumors. PMID- 26366343 TI - Granulocyte-colony stimulating factor producing anaplastic carcinoma of the pancreas treated by distal pancreatectomy and chemotherapy: report of a case. AB - Granulocyte-colony stimulating factor (G-CSF) producing pancreatic cancers are extremely rare. These tumors have an aggressive clinical course but no established treatment. We encountered a patient with a G-CSF-induced pancreatic cancer who was treated by surgical resection, followed by steroid treatment and chemotherapy. A 68-year-old Asian male presented at a local hospital with a 3 month history of fever, loss of appetite, and 10-kg weight loss. Laboratory data showed leukocytosis and elevation of C-reactive protein. Computed tomography (CT) revealed a 50-mm mass in the tail of the pancreas, but no signs of infective foci. He was transferred to our hospital for further evaluation. Contrast enhanced CT showed rapid growth of this tumor over 1 week, and (18) F-2-fluoro-2 deoxyglucose positron-emission tomography/computed tomography (FDG PET/CT) showed FDG accumulation in the tail of the pancreas (SUV max, 17.1) but at no other sites in his body. Magnetic resonance imaging showed a heterogeneous mass, similar to that observed by CT. Three weeks later, the patient underwent a distal pancreatectomy with splenectomy. The resected specimen was 154 mm in diameter, a threefold increase from the initial image. Histopathological examination identified the tumor as an anaplastic carcinoma of the pancreas. Following surgery, his leukocyte count and body temperature were reduced. He recovered well and was discharged from our hospital on postoperative day 18. Immunohistochemical expression of G-CSF in the resected specimen and elevated serum G-CSF concentration confirmed that the mass was a G-CSF producing anaplastic carcinoma of the pancreas. Subsequently, the patient experienced a high fever and loss of appetite. CT showed recurrence of cancer in the abdominal cavity, for which he was started immediately on tegafur-gimeracil-oteracil potassium combination S-1 and steroid. Unfortunately, he died on postoperative day 83. To our knowledge, this patient was the first with a G-CSF producing anaplastic carcinoma of the pancreas to be treated by surgical resection, steroid and adjuvant chemotherapy. PMID- 26366344 TI - Surgical treatment after hepatic arterial infusion chemotherapy for hepatocellular carcinoma extending into the right atrium. AB - A resected case of hepatocellular carcinoma which extended into the right atrium after treatment with hepatic arterial infusion chemotherapy (HAIC) is described. An 81-year-old man presented with right hypochondralgia. CT demonstrated a hypervascular tumor 11.5 cm in diameter extending into the right atrium through the right hepatic vein. The patient underwent HAIC with 100 mg of cisplatin (CDDP IA-call(r)) particles three times every month. The tumor showed a marked shrinkage and an involution of the venous thrombus around the orifice of the right hepatic vein. Right hemihepatectomy with tumor thrombectomy was performed as a salvage surgery using a total hepatic vascular exclusion technique. Histologically, the tumor turned into diffuse necrosis and fibrosis, so viable tumor cells were encountered neither in the main tumor nor venous thrombus. The therapeutic effect of HAIC was pathological complete remission. The patient has been doing well for 6 years after the surgery without evidence of tumor recurrence. The salvage operation was safely achievable for the initially unresectable advanced hepatocellular carcinoma extending into the right atrium. PMID- 26366345 TI - The first case of huge amebic intra-abdominal tumor with asymptomatic amebic colitis. AB - We report a rare case of huge amebic intra-abdominal tumor with asymptomatic amebic colitis. This appears to represent the first report of amebic intra abdominal tumor. A 31-year-old woman presented to a local doctor with only a sensation of abdominal fullness. Abdominal computed tomography (CT) showed a huge intra-abdominal tumor in the left abdominal cavity, and she was referred to our hospital. Colonofiberscopy for detailed examination showed multiple slight, discrete ulcers in the cecum. Ameboid trophozoites were identified from biopsy specimens, and asymptomatic amebic colitis was diagnosed. Oral metronidazole (MTZ) was administered at 1500 mg/day for 10 days. CT 14 days after starting MTZ showed no change in the intra-abdominal tumor, and resection of the tumor was therefore performed. Pathological examination revealed Entamoeba histolytica with engulfed erythrocytes complicated by hemorrhagic cyst. If an intra-abdominal tumor is present and colitis is observed, amebic intra-abdominal tumor should be considered among the differential diagnoses. PMID- 26366346 TI - Internal hernia after laparoscopic-assisted proximal gastrectomy with jejunal interposition for gastric cancer: a case report. AB - Internal hernia after gastrectomy is a rare complication. It can progress rapidly to vascular disturbance, necrosis, and perforation, therefore early diagnosis and surgical treatment is essential. We present a case of internal hernia following laparoscopic-assisted proximal gastrectomy with jejunal interposition reconstruction in a 68-year-old man, who presented with acute abdominal pain and vomiting. Computed tomography showed a whirl sign, ascites, and a closed-loop formation of the small intestine. We diagnosed an internal hernia and performed emergency surgery. Laparotomy revealed chyle-like ascites and extensive small intestine with poor color. We recognized that about 20 cm of jejunum from the ligament of Treitz was strangulated behind the pedicle of the jejunum lifted during laparoscopic-assisted proximal gastrectomy. We relieved the strangulation, whereupon the color of the strangulated intestine was restored. Therefore, we did not perform intestinal resection and reconstruction. Finally, we fixed the jejunal pedicle and mesentery of the transverse colon. We report this case as there are few reported cases of internal hernia after laparoscopic-assisted proximal gastrectomy. PMID- 26366347 TI - Right axillary lymph node metastasis of carcinoma of the cecum with histologically proven cutaneous lymphatic invasion by carcinoma cells: a case report. AB - Axillary lymph node metastasis from colorectal carcinoma is extremely rare, and this scarcity hinders understanding of its pathogenesis and, thus, the application of appropriate management. Here, we present a case with axillary lymph node metastasis of cecal carcinoma associated with macroscopic invasion of the skin of the abdominal wall with histological evidence of such invasion, findings which support our hypothesis that the axillary lymph node metastasis developed via the lymph channels in the skin of the abdominal wall. A 76-year-old woman with cecal carcinoma (T4N1M0), complicated with an abdominal wall abscess, underwent right hemicolectomy with partial resection of the abdominal wall. Histology demonstrated multiple sites of lymphatic invasion in the skin. Two months later, an enlarged right axillary lymph node was noticed on CT, and an excisional biopsy was obtained, which later confirmed metastatic adenocarcinoma. This is the first case report of axillary lymph node metastasis of carcinoma of the cecum with histologically proven invasion via the lymphatic system in the skin. If axillary lymph node metastasis results from aberrant lymphatics due to invasion from an adjacent organ, and not the result of systemic malignant disease, it may be considered as a surgically curable pathology. Therefore, the authors advocate that patients with axillary lymph node metastasis should be evaluated with regard to the possibility of surgical curability. PMID- 26366348 TI - Mirizzi syndrome with an unusual type of biliobiliary fistula-a case report. AB - Gallstone obstruction of the cystic duct, resulting in chronic cholecystitis and pressure necrosis leads to the formation of biliobiliary fistula (BBF). We herein reported a case of Mirizzi syndrome (MS) with an unusual type of BBF (Corlette type I) that was successfully managed by a staged treatment strategy. The patient was diagnosed with a solitary gallstone, marked atrophy of the gallbladder, and BBF and underwent mucosal incineration of the atrophic gallbladder and simple closure, followed by extirpation of gallbladder. Although an optimal treatment strategy has not yet been established for MS with BBF because of its rarity and anatomical variations in fistulas, the current treatment strategy may be applicable. In conclusion, clinicians need to carefully diagnose and evaluate chronic cholecystitis in MS with BBF and adopt an optimal treatment strategy to avoid the complication associated with this disease. PMID- 26366349 TI - A surgical case of eosinophilic angiocentric fibrosis of the lung. AB - Eosinophilic angiocentric fibrosis (EAF) is an uncommon inflammatory disease that develops from the respiratory organs and affects them. Almost all reports about EAF describe lesions affecting the upper respiratory tract. We present the first case of EAF of the lung treated by surgical excision. A 69-year-old female consulted our hospital following the detection of an abnormal chest shadow with chronic cough. Chest computed tomography showed a pulmonary growing mass in the right hilar area, which corresponded to an enhanced accumulation on positron emission tomography. We doubted a pulmonary malignant tumor and performed a right upper lobectomy. Pathological and other clinical presentations revealed EAF of the lung without coexisting systemic diseases. The patient had an uncomplicated postoperative course, and the presenting cough had improved. EAF can involve the lung and cause symptomatic airway obstruction. For a hilar region mass with imaging characteristics similar to those of lung cancer, a differential diagnosis must be considered. PMID- 26366350 TI - Single-site laparoscopic colectomy for rectosigmoid cancer with middle aortic syndrome: report of a case. AB - INTRODUCTION: Single-site laparoscopic colectomy (SLC) is a promising minimally invasive and safe treatment for colorectal cancer. Improvements of the working instruments and procedures for SLC have helped to overcome challenges regarding the difficulty of operation, supporting the gradual acceptance of this technique. In contrast, narrow working space of the abdominal cavity sometimes prevents securing an adequate surgical view. To obtain precise anatomical information and enable complete mesocolic excision (CME), we routinely perform three-dimensional computed tomography prior to SLC. CASE PRESENTATION: A 69-year-old Japanese woman was clinically diagnosed with rectosigmoid cancer. Unexpectedly, preoperative examination revealed asymptomatic stenosis of the great artery, which was diagnosed as middle aortic syndrome. Because radical colectomy requires dissection of vessels that supply blood flow to the legs, a vascular stent was inserted prior to operation. We chose SLC due to the reduced risk of damaging epigastric arteries, which may eventually become collaterals in the event of stent re-stenosis. We accomplished SLC with CME, and the patient was discharged on the tenth day after operation without complications. CONCLUSION: The present case is the first to proceed by SLC for colorectal cancer complicated by vascular obstructive disease. Preoperative imaging enabled us to identify an unexpected rare disease and to still accomplish SLC with CME, thus reinforcing the importance of preoperative imaging to optimize the use of SLC. In addition, SLC may become one of the most adequate procedures for patients complicated by vascular obstructive disease. PMID- 26366351 TI - Successful surgical internal drainage of postoperative pancreatic pseudocyst through pancreaticojejunostomy with distal pancreatectomy: a case report. AB - Pancreatic pseudocyst is usually treated by percutaneous external drainage, endoscopic internal or external drainage, or surgical internal drainage such as cystogastrostomy. Surgical external drainage is an option if these procedures fail. We describe a case of a 70-year-old man with a pancreatic body pseudocyst that developed postoperatively. It was improved by endoscopic external drainage, and the stent was changed to an internal stent. However, surgery was required as the pseudocyst grew again. A direct approach to the pseudocyst was not possible because of severe adhesion. A distal pancreatectomy with pancreaticojejunostomy was performed, and an external pancreatic stent tube was inserted from the cut end into the duodenum to drain the pseudocyst. One month later, the pseudocyst disappeared, and the stent was removed. PMID- 26366352 TI - Repeated hepatic resections and radio-frequency ablations may improve the survival of adult undifferentiated embryonal sarcoma of the liver: report of two cases. AB - Undifferentiated embryonal sarcoma of the liver (UESL) in adults, especially over 30 years old, is quite rare. We report two adult UESL patients that one of them survived 62 months and one is now surviving more than 65 months treated with repeated hepatic resections and radio-frequency ablations. Although UESL is an entirely unusual and aggressive tumor, multidisciplinary treatments including repeated hepatic resections and radio-frequency ablations may provide a longer survival. PMID- 26366353 TI - Differential diagnosis of primary intrapulmonary thymoma: a report of two cases. AB - Primary intrapulmonary thymomas (PITs), which are intrapulmonary tumors without an associated mediastinal component, are very rare. The diagnosis of a PIT can be difficult. Here, we report two cases of resected PITs that were difficult to differentiate from other lung tumors. The patients, of a 62-year-old man and a 64 year-old woman, had no significant symptoms and were both referred to our hospital due to the presence of an abnormal shadow on chest computed tomography (CT). The patients underwent (18)F-fluorodeoxyglucose positron emission tomography-CT (FDG-PET/CT) and subsequently tumor excision. A PIT was confirmed histopathologically in the surgical specimens from both patients. In one case, the tumor consisted of a type A thymoma without abnormal FDG uptake. In the other case, the tumor consisted of a type B2 thymoma presenting with weak FDG uptake. This report thus documents two cases of PITs with different histopathologic and FDG-PET/CT findings. Thoracoscopic surgery is essential in the differential diagnosis between PITs and other lung tumors. PMID- 26366354 TI - A patient with paroxysmal nocturnal hemoglobinuria being treated with eculizumab who underwent laparoscopic cholecystectomy: report of a case. AB - Paroxysmal nocturnal hemoglobinuria (PNH) is acquired hemolytic anemia characterized by symptoms such as anemia and hemoglobinuria. In recent years, eculizumab as an anti-complement (C5) monoclonal antibody has been used for PNH and shown to have marked effects. We performed laparoscopic cholecystectomy in a patient with PNH being treated with eculizumab, and could avoid the risk of perioperative hemolysis and thrombosis. [Patient] The patient was a 48-year-old female who had developed PNH when she was 39 years old. At the age of 46 years, eculizumab administration was initiated once every 2 weeks. During the administration period, neither the progression of anemia nor hemoglobinuria was observed. In March 2013, gallstones were detected, and she was referred to our hospital for surgery. Eculizumab was administered 10 days before surgery, and laparoscopic cholecystectomy was performed in May 2013. After the operation, for the prevention of thrombosis, elastic stockings and a foot pump were used without anticoagulant administration. After the operation, neither the progression of anemia nor hemoglobinuria was observed. On postoperative day 5, eculizumab was administered as planned, and she showed a favorable general condition and was discharged. [Discussion] Perioperative care in PNH patients was conventionally considered to involve a high risk of developing anemia, thrombosis, or infection. However, after the advent of eculizumab, the control of the symptoms of PNH became possible in many patients. In this patient with PNH being treated with eculizumab, safe perioperative management was possible without the development of complications. PMID- 26366355 TI - Retrocardiac lung hernia after thoracic esophagectomy: report of a rare case. AB - A retrocardiac lung hernia is an extremely rare complication after esophagectomy. A 56-year-old man was admitted to our hospital with advanced middle thoracic esophageal cancer and a giant bulla at the apical portion of the right lung. Since it appeared that dissection of the upper mediastinum would most likely require resection of the right bulla, a two-stage operation for esophageal cancer was planned. During the first-stage operation, thoracic esophagectomy and resection of the right giant bulla were performed. Fourteen days after the first stage operation, the patient underwent laparotomy as the second-stage operation to reconstruct a narrow gastric tube via a retrosternal route. After the second stage operation, the inflammatory reaction was prolonged. Therefore, a thoracoabdominal computed tomography scan was performed, showing retrocardiac pulmonary atelectasis. The patient was diagnosed with a retrocardiac left lung hernia in which the left lower lobe was displaced into the right thoracic cavity. Because the inflammatory reaction was due to effects of the lung hernia, a repair operation was performed via a left seventh intercostal thoracotomy. At thoracotomy, the left basal segment of the lung was atelectatic and reddish and had herniated into the right thoracic cavity through an opening between the aorta and pericardium. The herniated lung tip adhered strongly to the subcarina, and synechiotomy was performed. We believe that simultaneous removal of the right giant bulla with esophagectomy was the important cause of this complication. PMID- 26366356 TI - Paraneoplastic cerebellar degeneration and dermatomyositis as first manifestations of underlying breast malignancy: a report of two cases and a brief review of the subject. AB - Paraneoplastic syndromes are rare first manifestations of breast cancer. In this report, we present two cases of a 58-year-old woman and a 69-year-old woman presenting with acute symptoms of paraneoplastic cerebellar degeneration (PCD) and dermatomyositis, respectively, as the first sign of breast malignancy. The patient diagnosed with PCD presented initially with ataxia, was serum anti-Yo antibody negative, and subsequently investigated to have poorly differentiated intraductal breast carcinoma. Cerebellar symptoms regressed following breast cancer surgery and chemotherapy, highlighting the better neurological prognosis associated with anti-Yo antibody negative PCD. The rarity of these presentations highlights the necessity to include an occult malignancy in the differential diagnosis when attending to such patients. PMID- 26366357 TI - Stent graft placement and balloon dilation for pseudoaneurysm complicated by distal arterial stenosis of the hepatic artery after pancreaticoduodenectomy. AB - Hemorrhage from ruptured pseudoaneurysm is a rapidly progressing and potentially fatal complication after pancreaticoduodenectomy (PD). Stent graft placement for hepatic artery pseudoaneurysm has recently been reported as a valid alternative to transcatheter arterial embolization (TAE). We report a case of pseudoaneurysm of the common hepatic artery (CHA) with distal arterial stenosis treated by stent graft placement for pseudoaneurysm and balloon dilation for arterial stenosis due to pancreatic fistula after PD. A 67-year-old man underwent PD for intraductal papillary mucinous neoplasm with concomitant early gastric cancer. After the operation, pancreatic fistula developed, for which conservative management by drainage was continued. On the postoperative day 30, melena started. Emergency abdominal angiography revealed a pseudoaneurysm in the CHA, as well as distal arterial stenosis extending from the proper hepatic artery (PHA) to bilateral hepatic arteries. The portal vein was also stenotic due to pancreatic fistula, for which TAE was not judged suitable because of the risk of liver failure. Therefore, stent graft placement and balloon dilation were chosen. Three pieces of coronary covered stent were placed in a coaxial overlapping manner followed by balloon dilation of the proper and left hepatic arteries. Balloon dilation of the right hepatic artery failed by technical reasons. Completion arteriography confirmed the patency from the CHA to the left hepatic artery as well as the exclusion of the pseudoaneurysm. A liver abscess that developed in the right hepatic lobe after intervention was successfully treated by percutaneous drainage, and the patient discharged on day 27 after stent graft placement. Non embolic management with preservation of the liver arterial flow may be an option for complicated pseudoaneurysm after PD. PMID- 26366358 TI - An incarcerated appendix and the ileocecum within a left inguinal hernia in an infant. AB - An 8-month-old boy with a left-sided incarcerated inguinal hernia involving the appendix, cecum, and terminal ileum was successfully managed via an inguinal approach during an emergency operation. A mobile cecum seemed to have contributed to the left-sided incarceration. Only 13 similar cases with the left-sided Amyand's hernia have been reported in the literature. PMID- 26366359 TI - Efficacy of nonsurgical tigecycline pleurodesis for the management of hepatic hydrothorax in patients with liver cirrhosis. AB - Chemical pleurodesis is one of the therapeutic tools to control hepatic hydrothorax. Tetracycline and derivatives have been widely accepted as an effective and safe treatment for the purpose, but availability is the big concern. Tigecycline is an antibiotic derivative of tetracycline, which has demonstrated to be an effective pleurodesing agent in animal models. The aim of the study was to document two successful tigecycline pleurodesis in patients with decompensated liver cirrhosis, who were not candidates for liver transplantation. Both patients were undergoing palliative treatment for cirrhosis and developed massive pleural effusion on the right side. They underwent chemical pleurodesis in the first instance. Diagnostic thoracocentesis was done to rule out differentials and to confirm the clinical suspicion, following which, complete drainage of pleural fluids was achieved. Tigecycline of 3 mg/kg was instilled intrapleurally via the thoracic catheter, as per the protocol. The medical records and images were thoroughly reviewed. There was no recurrence of the effusion for at least 3 months, with no detected complications in the short- or long-term follow-up. In conclusion, pleurodesis with tigecycline seems to be effective and safe for the management of symptomatic hepatic hydrothorax and should therefore be promoted in the setting of liver cirrhosis at least for a short-term relief, especially in patients who do not meet the criteria for liver transplantation. PMID- 26366360 TI - Simultaneous occurrence of distant metastases to the small intestine and the thoracic esophagus from anaplastic thyroid carcinoma: a case report. AB - Anaplastic thyroid carcinoma (ATC) is an aggressive malignancy and characterized by spreading to regional lymph nodes and distant metastases, but we were unable to find a previous report of simultaneous metastases of transformed ATC to either the small intestine or thoracic esophagus in the English language literature. A 60-year-old man suffered from well-differentiated thyroid carcinoma and underwent total thyroidectomy. Eight years later, local recurrence of thyroid cancer showed intense fluorodeoxyglucose/positron emission tomography (FDG-PET) uptake at the paratracheal region, which was suspected as a remnant tumor of the thyroid that transformed from differentiated to ATC. At that time, the patient underwent resection of the small intestine to remove an abdominal mass and consequently developed stenosis of the thoracic esophagus caused by the esophageal tumor. Histological scrutiny of specimens from both tumors in the small intestine and thoracic esophagus demonstrated the same pattern as that of undifferentiated carcinoma. Regarding histological verification and a change in the FDP-PET uptake level, it is strongly possible that our case demonstrated coincident metastases of ATC to both the small intestine and esophagus. In conclusion and to the best of our knowledge, this report is the first to present evidence suggesting that ATC has the potential to metastasize to any organs, including the digestive tract. PMID- 26366361 TI - Huge epithelioid malignant peripheral nerve sheath tumor in the left axilla: a case report. AB - This report describes a patient with a rare huge epithelioid malignant peripheral nerve sheath tumor (MPNST) in the left axilla. A male in his 70s was admitted to our hospital for evaluation of a growing tumor in his left axilla. The tumor was solid and immovable. Examination of a biopsy specimen resulted in a diagnosis of epithelioid MPNST. Two weeks after the biopsy was performed, the tumor grew to 20 cm and became painful, and the patient was unable to feel pressure on his upper arm. Immediately before surgery to remove the tumor, computed tomography suggested the presence of lung metastases. The patient and his family were informed of his disease state, and they elected surgical treatment to ease the symptoms associated with tumor enlargement. Systemic metastases appeared soon after the surgery, and the patient died within 11 weeks. Comparative genomic hybridization (CGH) analysis showed that this tumor was chromosomally unstable, with impairments in gene expression. PMID- 26366362 TI - Umbilical hernia with cholelithiasis and hiatal hernia: a clinical entity similar to Saint's triad. AB - We experienced two cases involving the simultaneous presence of cholelithiasis, hiatal hernia, and umbilical hernia. Both patients were female and overweight (body mass index of 25.0-29.9 kg/m(2)) and had a history of pregnancy and surgical treatment of cholelithiasis. Additionally, both patients had two of the three conditions of Saint's triad. Based on analysis of the pathogenesis of these two cases, we consider that these four diseases (Saint's triad and umbilical hernia) are associated with one another. Obesity is a common risk factor for both umbilical hernia and Saint's triad. Female sex, older age, and a history of pregnancy are common risk factors for umbilical hernia and two of the three conditions of Saint's triad. Thus, umbilical hernia may readily develop with Saint's triad. Knowledge of this coincidence is important in the clinical setting. The concomitant occurrence of Saint's triad and umbilical hernia may be another clinical "tetralogy." PMID- 26366363 TI - Emergency surgery for tubo-ovarian abscess identified extended-spectrum beta lactamase-producing Escherichia coli: the first case presentation revealing causative bacteria. AB - We report herein a 41-year-old female with a tubo-ovarian abscess (TOA), which microbial cultures showed to contain extended-spectrum beta-lactamase (ESBL) producing E. coli, a causative agent of community-acquired infection. The patient initially presented with acute abdominal pain and back pain. Pelvic computed tomography and transvaginal ultrasonography revealed multiple cystic lesions in the bilateral ovaries that suggested TOA. An emergency laparotomy was therefore performed due to the potential for life-threatening septic shock from the TOA associated pelvic inflammatory disease. Microbial cultures of postoperative fluid discharge from the placed intra-abdominal catheter, vaginal secretions, urine, blood, and feces detected ESBL-producing E.coli. In summary, we successfully performed emergency surgery for life-threatening septic TOA caused by ESBL producing E. coli infection. PMID- 26366364 TI - Plexiform schwannoma involving the trachea and recurrent laryngeal nerve: a case report. AB - Plexiform schwannoma is an infrequent variant of schwannoma characterized grossly and microscopically by multi-nodular growth. Although plexiform schwannoma has such growth patterns, it is a benign tumor as well as a conventional schwannoma. It rarely infiltrates adjacent organs or arises from the organ itself. In this report, we describe a case in which plexiform schwannoma involved the tracheal wall and left recurrent laryngeal nerve to a great extent. As it was expected to be difficult to achieve complete resection even if the longer tracheal resection were performed, we preserved the trachea and resected as much of the tumor as possible. This report is thought to be the first to describe plexiform schwannoma infiltrating or growing from the trachea. Although the treatment decisions we made might be controversial, we believed we could make an accurate diagnosis and adequate treatment decision through surgery. PMID- 26366365 TI - Conservative treatment of idiopathic spontaneous pneumoperitoneum in a bedridden patient: a case report. AB - Idiopathic spontaneous pneumoperitoneum is a rare condition that is characterized by intraperitoneal gas for which no clear etiology has been identified. We report here a case of idiopathic spontaneous pneumoperitoneum, which was successfully managed by conservative treatment. A 77-year-old woman who was bedridden with speech disability as a sequela of brain hemorrhage presented at our hospital with a 1-day history of abdominal distention. On physical examination, she had stable vital signs and slight epigastric tenderness on deep palpation without any other signs of peritonitis. A chest radiograph and computed tomography showed that a large amount of free gas extended into the upper abdominal cavity. Esophagogastroduodenoscopy revealed no perforation of the upper gastrointestinal tract. The patient was diagnosed with idiopathic spontaneous pneumoperitoneum, and conservative treatment was selected. The abdominal distension rapidly disappeared, and the patient resumed oral intake on the 5th hospital day without deterioration of symptoms. Knowledge of this rare disease and accurate diagnosis with findings of clinical imaging might contribute towards refraining from unnecessary laparotomy. PMID- 26366366 TI - A delayed-onset rectourethral fistula after intersphincteric resection for very low rectal cancer: a case report and literature review. AB - Rectourethral fistula is one of the complications that can occur after prostatectomy in the urologic discipline. However, a delayed-onset rectourethral fistula after intersphincteric resection (ISR) for low rectal cancer is extremely rare. Here, we report one such case in a 57-year-old man. After ISR for low rectal cancer with a diverting stoma (DS), the DS was closed. After approximately 1 year, frequent pneumaturia and right orchitis were observed. Results of contrast enemas and abdominal computed tomography examinations revealed a rectourethral fistula from an anastomosis to the urethra. The colonoscopic appearance revealed a pinhole fistula on the anastomotic line, with thick pus. We performed a transverse colostomy, and the pneumaturia and right orchitis were no longer observed. Two months later, colonoscopy, contrast enemas, and cystoscopy revealed no rectourethral fistula. To the best of our knowledge, our case is the first report of a delayed-onset rectourethral fistula after ISR. PMID- 26366367 TI - Rerupture of nonparasitic liver cyst treated with cyst fenestration: a case report. AB - We herein describe a case involving spontaneous rerupture of a nonparasitic liver cyst successfully treated with cyst fenestration and an omental flap. A 59-year old Japanese woman was transferred to our hospital for evaluation of acute abdominal pain. She had a history of conservative treatment with antibiotics for spontaneous rupture of a liver cyst 1 month previously. On arrival, she exhibited abdominal tenderness and muscular defense. Enhanced computed tomography showed ascites and a large ruptured hepatic cyst (diameter of 10 cm). We diagnosed rerupture of a liver cyst and performed laparotomy for cyst fenestration and intraperitoneal drainage. During the operation, we found the perforation site on the ventral side of the cyst and brown, muddled ascitic fluid. Cholangiography showed no bile leakage on the inner wall. Pathological investigation revealed no evidence of malignancy. The patient recovered without any adverse events and was discharged on postoperative day 8. No recurrences or complications occurred for 2 years. PMID- 26366368 TI - Laparoscopic and endoscopic cooperative surgery for gastrointestinal stromal tumor with complete situs inversus: report of a case. AB - We herein report our experience of performing laparoscopic and endoscopic cooperative surgery for a gastrointestinal stromal tumor with complete situs inversus. A 78-year-old man was referred to our department for treatment of a gastric submucosal tumor. Based on chest X-ray and computed tomography (CT) findings, complete situs inversus was also diagnosed. Upper gastrointestinal endoscopy and imaging showed a 45-mm gastric submucosal tumor in the upper stomach near the esophagogastric junction. We performed local resection of the gastric submucosal tumor by laparoscopic and endoscopic cooperative surgery. Pathological examination revealed that the tumor was an intermediate-risk gastrointestinal stromal tumor, and the patient was discharged on postoperative day 12. The patient is still alive without recurrence or any complications 9 months after surgery. PMID- 26366369 TI - Omental rhabdomyosarcoma (primary rhabdoid tumor of greater omentum): a rare case report. AB - The greater omentum is an uncommon location for primary tumors. Metastatic tumors of the omentum are common. In contrast, primary tumors of the omentum are very rare. Sporadic cases of primary rhabdomyosarcoma (RMS) arising in the abdomen have been reported, but these cases are limited almost exclusively to the pediatric population. We report a well-documented case of primary intra-abdominal RMS in a 21-year-old man who presented with complaints of abdominal pain and lump in left hypochondrium region. Imaging revealed it to be a large mass in the left hypochondrium region displacing the bowel loops. Further investigations revealed omental RMS. The mass had originated from the greater omentum and was excised. Our case is doing well and is presently receiving chemotherapy. PMID- 26366370 TI - Successful resection of a huge metastatic liposarcoma in the pericardium resulting in improvement of diastolic heart failure: a case report. AB - Although liposarcoma often metastasizes to various organs, cardiac metastasis, including to the pericardium, is rare. We present a case of a third recurrence of pericardial metastasis from the thigh, which required surgical resection because of cardiac failure. Surgery was effective for improving cardiac function and reintroducing chemotherapy. This is the first reported case of metastatic pericardial liposarcoma, which was successfully resected three times. We believe that aggressive surgical treatment, when it can resolve cardiac impairment, potentially leads to a more favorable prognosis. PMID- 26366371 TI - Pleuropneumonectomy for a large thymoma with multiple pleural dissemination using median sternotomy followed by posterolateral thoracotomy. AB - We present 2 cases of a large thymoma with invasion to the hilum of the lung and pleural dissemination. Case 1: a 47-year-old woman was diagnosed with a type B3 thymoma with abundant left pleural effusion and multiple pleural masses, Masaoka stage IVa. A radical resection was planned after chemical pleurodesis and systemic chemotherapy. The left main pulmonary artery and left upper and inferior veins were dissected and resected in the pericardium, while the left main bronchus was cut behind the pericardium through a median sternotomy. Next, the median incision was closed and a left posterolateral thoracotomy was made, thus allowing the pleuropneumonectomy to be safely performed. Case 2: a 47-year-old woman was diagnosed with a type B3 thymoma with lymph node swelling and multiple pleural masses, indicating Masaoka stage IVb. Following induction chemotherapy, a thymothymectomy combined with a right pleuropneumonectomy was performed under a median sternotomy followed by a right posterolateral thoracotomy. The left brachiocephalic vein (BCV) was reconstructed with a ringed polytetrafluoroethylene (PTFE) graft, followed by resection of the right BCV. Next, the right main pulmonary artery and right upper and inferior veins were resected in the pericardium, and the right main bronchus was cut behind the pericardium, followed by reconstruction of the right BCV. Finally, the median incision was closed and a right posterolateral thoracotomy was made, thus allowing performance of a safe pleuropneumonectomy. The median sternotomy allowed safe dissection of pulmonary vessels surrounding the hilum of the lung and, in combination with a posterolateral thoracotomy, was required for performing a pleuropneumonectomy in patients with a huge thymoma with pleural dissemination. PMID- 26366372 TI - Fractal analysis and the diagnostic usefulness of silver staining nucleolar organizer regions in prostate adenocarcinoma. AB - Pathological diagnosis of prostate adenocarcinoma often requires complementary methods. On prostate biopsy tissue from 39 patients including benign nodular hyperplasia (BNH), atypical adenomatous hyperplasia (AAH), and adenocarcinomas, we have performed combined histochemical-immunohistochemical stainings for argyrophilic nucleolar organizer regions (AgNORs) and glandular basal cells. After ascertaining the pathology, we have analyzed the number, roundness, area, and fractal dimension of individual AgNORs or of their skeleton-filtered maps. We have optimized here for the first time a combination of AgNOR morphological denominators that would reflect best the differences between these pathologies. The analysis of AgNORs' roundness, averaged from large composite images, revealed clear-cut lower values in adenocarcinomas compared to benign and atypical lesions but with no differences between different Gleason scores. Fractal dimension (FD) of AgNOR silhouettes not only revealed significant lower values for global cancer images compared to AAH and BNH images, but was also able to differentiate between Gleason pattern 2 and Gleason patterns 3-5 adenocarcinomas. Plotting the frequency distribution of the FDs for different pathologies showed clear differences between all Gleason patterns and BNH. Together with existing morphological classifiers, AgNOR analysis might contribute to a faster and more reliable machine-assisted screening of prostatic adenocarcinoma, as an essential aid for pathologists. PMID- 26366374 TI - Identification of transcripts regulated by CUG-BP, Elav-like family member 1 (CELF1) in primary embryonic cardiomyocytes by RNA-seq. AB - CUG-BP, Elav-like family member 1 (CELF1) is a multi-functional RNA binding protein that regulates pre-mRNA alternative splicing in the nucleus, as well as polyadenylation status, mRNA stability, and translation in the cytoplasm [1]. Dysregulation of CELF1 has been implicated in cardiomyopathies in myotonic dystrophy type 1 and diabetes [2-5], but the targets of CELF1 regulation in the heart have not been systematically investigated. We previously demonstrated that in the developing heart CELF1 expression is restricted to the myocardium and peaks during embryogenesis [6-8]. To identify transcripts regulated by CELF1 in the embryonic myocardium, RNA-seq was used to compare the transcriptome of primary embryonic cardiomyocytes following siRNA-mediated knockdown of CELF1 to that of controls. Raw data files of the RNA-seq reads have been deposited in NCBI's Gene Expression Omnibus [9] under the GEO Series accession number GSE67360. These data can be used to identify transcripts whose levels or alternative processing (i.e., alternative splicing or polyadenylation site usage) are regulated by CELF1, and should provide insight into the pathways and processes modulated by this important RNA binding protein during normal heart development and during cardiac pathogenesis. PMID- 26366373 TI - New insights into the FLPergic complements of parasitic nematodes: Informing deorphanisation approaches. AB - FMRFamide-like peptide (FLP) receptors are appealing as putative anthelmintic targets. To date, 31 flp-encoding genes have been identified in Caenorhabditis elegans and thirteen FLP-activated G-protein coupled receptors (FLP-GPCRs) have been reported. The lack of knowledge on FLPs and FLP-GPCRs in parasites impedes their functional characterisation and chemotherapeutic exploitation. Using homology-based BLAST searches and phylogenetic analyses this study describes the identification of putative flp and flp-GPCR gene homologues in 17 nematode parasites providing the first pan-phylum genome-based overview of the FLPergic complement. These data will facilitate FLP-receptor deorphanisation efforts in the quest for novel control targets for nematode parasites. PMID- 26366375 TI - Catel-Manzke Syndrome: Further Delineation of the Phenotype Associated with Pathogenic Variants in TGDS. AB - Catel-Manzke syndrome is a rare autosomal recessive disorder characterized by Pierre Robin sequence with hyperphalangy and clinodactyly of the index finger. Recently, homozygous or compound heterozygous pathogenic variants in TGDS have been discovered to cause Catel-Manzke syndrome. Here, we describe a 12-month-old male with molecularly confirmed Catel-Manzke syndrome who presented with Pierre Robin sequence (but without cleft palate) and hyperphalangy, and we compare his phenotype with the seven previously described patients with pathogenic variants in TGDS. Our patient is on the severe end of the phenotypic spectrum, presenting with respiratory complications and failure to thrive. Furthermore, our finding of a homozygous p.Ala100Ser pathogenic variant in our patient supports that it is a common mutation in Catel-Manzke syndrome. PMID- 26366376 TI - No Evidence of Antibodies against GAD65 and Other Specific Antigens in Children with Autism. AB - BACKGROUND: The presence of autoantibodies has been proposed as evidence for a role of autoimmunity in autism. This report investigates the prevalence of autoantibodies in children with autism using the luciferase immunoprecipitation systems (LIPS) immunoassay technology. A panel of autoantibody targets against several known and candidate neurological autoantigens, autoimmune-associated autoantigens and viruses was employed. METHODS: Serological analysis was performed on typically developing children (n = 55), developmentally delayed children without autism (n = 24) and children diagnosed with autism (n=104). Autoantibodies were measured against glutamic acid decarboxylase-65 (GAD65), a CNS autoantigen proposed to be associated with autism and against Ro52, glial fibrillary acidic protein, tyrosine hydroxylase, aquaporin-4, and gamma-enolase, the mouse mammary tumor virus and the xenotropic murine leukemia virus. Antibody levels and seropositivity prevalence were analyzed for statistically significant differences between the three groups. RESULTS: The majority of the children (98%) were seronegative for all targets in the antigen panel. No GAD65 seropositive children were detected in the cohort. Several low level seropositive sera against several of the protein targets were identified in isolated children in each of the three groups, but there was no difference in prevalence. CONCLUSION: Using this panel of antigens and a sensitive, robust assay, no evidence of unusual immunoreactivity was detected in children with autism, providing evidence against a role of autoimmunity against several previously implicated proteins in autism spectrum disorder pathogenesis. GENERAL SIGNIFICANCE: The idea that autoantibodies represent an underlying cause or are biomarkers for autism pathophysiology is not supported by this report. PMID- 26366377 TI - EFFECT OF SELENIUM SUPPLEMENTATION ON PROTEOMIC SERUM BIOMARKERS IN ELDERLY MEN. AB - OBJECTIVES: To determine the effect of selenium supplementation on the human proteomic profile. DESIGN: Serum samples were collected in this pilot study from a randomized placebo controlled Phase 2 clinical trial (Watchful Waiting (WW)). SETTING: Subjects were followed every three months for up to five years at the University of Arizona Prostate Cancer Prevention Program. PARTICIPANTS: One hundred and forty men (age < 85 years) had biopsy-proven prostate cancer, a Gleason sum score less than eight, no metastatic cancer, and no prior treatment for prostate cancer. INTERVENTION: As part of the WW trial, men were randomized to placebo, selenium 200 MUg/day or selenium 800 MUg/day. For the purpose of the current study, 40 subjects enrolled in the WW study (20 from the placebo group and 20 from Se 800 MUg/day group) were selected. MEASUREMENTS: Baseline serum samples were collected at each follow-up visit and stored at -80 degrees Celsius. A multiplexed proteomic panel investigated changes in 120 proteins markers simultaneously. RESULTS: Thirteen proteins (Apolipoprotein J, IL-10, IL-1 alpha, MMP-3, IL-12p70, IL-2 receptor alpha, cathepsin B, eotaxin, EGFR, FGF-basic, myeloperoxidase, RANTES, TGF-beta) were determined to be either statistically (p value < 0.05) or marginally significantly (0.05 < p-value <0.1) changed in the selenium supplemented group as compared to placebo. CONCLUSION: Although independent validation of these results is needed, this study is the first of its kind to utilize high throughput fluorescence based protein multiplex panel in analyzing changes in the proteomic profile due to selenium supplementation. Results from this study provide insight into the ability of selenium to modulate numerous protein markers and thus impact various biological processes in humans. PMID- 26366378 TI - PHARMACOLOGICAL INTERVENTIONS IN FRAILTY AND SARCOPENIA: REPORT BY THE INTERNATIONAL CONFERENCE ON FRAILTY AND SARCOPENIA RESEARCH TASK FORCE. AB - Sarcopenia and frailty often co-exist and both have physical function impairment as a core component. Yet despite the urgency of the problem, the development of pharmaceutical therapies for sarcopenia and frailty has lagged, in part because of the lack of consensus definitions for the two conditions. A task force of clinical and basic researchers, leaders from the pharmaceutical and nutritional industries, and representatives from non-profit organizations was established in 2012 with the aim of addressing specific issues affecting research and clinical activities on frailty and sarcopenia. The task force came together on April 22, 2015 in Boston, Massachusetts, prior to the International Conference on Frailty and Sarcopenia Research (ICFSR). The theme of this meeting was to discuss challenges related to drugs designed to target the biology of frailty and sarcopenia as well as more general questions about designing efficient drug trials for these conditions. The present article reports the results of the task force's deliberations based on available evidence and preliminary results of ongoing activities. Overall, the lack of a consensus definition for sarcopenia and frailty was felt as still present and severely limiting advancements in the field. However, agreement appears to be emerging that low mass alone provides insufficient clinical relevance if not combined with muscle weakness and/or functional impairment. In the next future, it will be important to build consensus on clinically meaningful functional outcomes and test/validate them in long-term observational studies. PMID- 26366379 TI - Minimally invasive parathyroidectomy with or without intraoperative parathyroid hormone for primary hyperparathyroidism. AB - PURPOSE: The improvement of intraoperative parathyroid hormone (IOPTH) assay and localization studies has enabled a minimally invasive parathyroidectomy (MIP) in primary hyperparathyroidism (pHPT). The aim of this study is to analyze the demographics, clinical presentations, and surgical outcomes of the pHPT patients who received surgical management with versus without IOPTH. METHODS: Analysis of a database was performed on 53 patients who underwent parathyroidectomy for pHPT from 2004 to 2013. Preoperative localization was done by both sestamibi scan and ultrasonography. We divided the patients into two groups (without IOPTH versus with IOPTH) and analyzed the surgical outcomes statistically between two groups. RESULTS: The concordance rate of Technetium 99m sestamibi scan and ultrasonography was 73.6% and 90.6%, respectively. The overall cure rate of group 1 (without IOPTH) was 94.9% and that of group 2 (with IOPTH) was 100%. The decline of PTH at postoperative 5 minutes and 10 minutes was 75.2% +/- 14.9% and 84.9% +/- 8.6% in cured patients. On the other hand, that of noncured patients at 5 minutes and 10 minutes was 17.2% +/- 9.7% and 8.2% +/- 2.2%. There was a significant difference in the drop rate of IOPTH between cured and persistent patients (P < 0.01). Pathological examination showed adenoma in 41 of 53 patients (77.4%) and hyperplasia in 10 of 53 patients (18.9%). CONCLUSION: Even though the localization studies were successful, IOPTH monitoring is essential to avoid a surgical failure in MIP. PMID- 26366380 TI - Laparoscopic gastric tube formation with pyloromyotomy for reconstruction in patients with esophageal cancer. AB - PURPOSE: To analyze the benefit and feasibility of this procedure compared with those of open method. METHODS: Abdominal procedure includes laparoscopic gastric mobilization, celiac axis lymph node dissection, formation of the gastric tube, and pyloromyotomy. The actual procedure performed during open surgery is the same as those of laparoscopic surgery except for the main incision. Minimally invasive esophagectomy (MIE) was performed on 54 patients with esophageal cancer. The short-term outcomes, including postoperative complications were analyzed and compared with 44 cases of open method. RESULTS: Although the total operative time was not different between 2 groups (349.8 minutes vs. 374.8 minutes, P = 0.153), the operation time of abdominal procedure was shorter in laparoscopic group (90.6 minutes vs. 162.1 minutes, P < 0.001). Operation related complications and hospital stay were not significantly different between the 2 groups. The number of transfused patients was significantly smaller in laparoscopic group (11.1% vs. 27.9%, P = 0.030). CONCLUSION: Laparoscopic gastric tubing with pyloromyotomy is a feasible and safe treatment option for patients with esophageal cancer. PMID- 26366381 TI - Oncologic outcomes of early adjuvant chemotherapy initiation in patients with stage III colon cancer. AB - PURPOSE: Although adjuvant chemotherapy reduces the risk of disease recurrence in stage III colon cancer patients, published guidelines do not specify when it should be initiated. This study aimed to assess the effect of adjuvant chemotherapy initiation time on disease recurrence and survival in stage III colon cancer patients undergoing curative surgical resection. METHODS: The medical records of stage III colon cancer patients undergoing curative resection between February 2004 and December 2009 were reviewed. RESULTS: Of the 133 enrolled patients, 27 (20.3%) began adjuvant chemotherapy within 3 weeks of surgery, whereas 106 (79.7%) did after 3 weeks following surgery. Patients receiving chemotherapy within 3 weeks of surgery were less likely to experience recurrences than those beginning treatment later (11.1% vs. 33%, P = 0.018). The mean disease-free survival of patients receiving adjuvant therapy earlier was 54.6 months, whereas that of patients with later treatment was 43.5 months (P = 0.014). However, no significant differences in overall survival were observed between the 2 groups. CONCLUSION: Adjuvant chemotherapy should be initiated as soon as a patient's clinical condition allows. Patients with stage III colon cancer may benefit from adjuvant chemotherapy initiated within 3 weeks of surgery. PMID- 26366382 TI - Outcomes of pelvic exenteration for recurrent or primary locally advanced colorectal cancer. AB - PURPOSE: The objective of this study was to assess the clinical outcomes of pelvic exenteration for patients with primary locally advanced colorectal cancer (LACRC) or locally recurrent colorectal cancer (LRCRC), and to identify clinically relevant prognostic factors. METHODS: Between January 2001 and December 2010, 40 consecutive patients with primary LACRC or LRCRC underwent pelvic exenteration at the National Cancer Center, Republic of Korea. We retrospectively reviewed their medical records. RESULTS: The median age was 59 years and the median follow-up time was 26 months (range, 1-117 months). The overall complication and in-hospital mortality rates were 70% (28/40) and 7.5% (3/40), respectively. The complication rates were similar between patients with primary LACRC (69.6%) and those with LRCRC (70.6%). The overall recurrence rate was 50% (17/34), and was lower in patients with primary LACRC than in patients with LRCRC (33.3% vs. 76.9%, P = 0.032). The 5-year overall survival was significantly different between primary LACRC and patients with LRCRC (58.7% vs. 11.8%, P = 0.022). Multivariate analysis revealed that radicality (R0 vs. R1/R2) was an independent prognostic factor for overall survival (P = 0.020). CONCLUSION: The complication and operative mortality rates of pelvic exenteration remained high, but pelvic exenteration might provide an opportunity for long-term survival and good local control. Complete (R0) resection was the only independent prognostic factor for overall survival. PMID- 26366383 TI - Comparison of Coskun and Lichteinstein hernia repair methods for groin hernia. AB - PURPOSE: Coskun hernia repair technique has been reported to be an effective new fascia transversalis repair with its short-term follow-up results. Our aim is to determine the results of Coskun hernia repair technique and to compare it with Lichtenstein technique. METHODS: At this comparative retrospective study a total of 493 patients, who had groin hernia repair procedure using Coskun or Lichtenstein technique, between January 1999 and March 2010 were enrolled into the study. Patients were reached by telephone and invited to get a physical examination. RESULTS: Out of 493 groin hernia repairs, 436 (88.5%) were carried out by residents and 57 (11.5%) by attending surgeons. Lichtenstein technique was the choice in 241 patients and 252 patients underwent Coskun hernia repair technique. Groin hernia recurrence was detected in 8 patients (3.1%) in Coskun hernia repair group and 7 patients (2.9%) in Lichtenstein group. Comparison of early complication rates in Coskun group (3.9%) and Lichtenstein group (4.5%) showed no significant difference. Late complication rates were significantly higher in Lichtenstein group (1.2% vs. 4.9%). The operation time was shorter in Coskun group (44 minutes) than in Lichtenstein group (60 minutes). Subgroup of patients, whose hernia repair operations were carried out by attending surgeons, had a recurrence rate of 0% and 3.8%, in Coskun group and Lichtenstein group, respectively. CONCLUSION: This study showed that Coskun hernia repair technique has a similar efficacy with Lichtenstein repair, on follow-up. PMID- 26366384 TI - De novo hepatitis B virus infection developing after liver transplantation using a graft positive for hepatitis B core antibody. AB - PURPOSE: The use of hepatitis B core antibody (HBcAb)-positive grafts is increasing, especially where hepatitis B is endemic. However, this remains controversial because of the risk of development of de novo HBV infection. METHODS: We collected information obtained between January 2000 and December 2012 and retrospectively analyzed data on 187 HBsAg-negative donors and recipients were analyzed retrospectively. De novo HBV infection was defined as development of HBsAg positivity with or without detection of HBV DNA. RESULTS: Forty patients (21.4%) received HBcAb-positive grafts. Survival rate did not differ by donor HBcAb status (P = 0.466). De novo HBV infection occurred in five patients (12.5%) who were not treated with anti-HBV prophylaxis, and was significantly more prevalent in hepatitis B surface antibody (HBsAb)- and HBcAb-negative than HBsAb- and HBcAb-positive recipients (50% vs. 4.2%, P = 0.049). All patients except one were treated with entecavir with/without antihepatitis B immunoglobulin and four were negative in terms of HBV DNA seroconversion. No patient died. CONCLUSION: HBcAb-positive grafts are safe without survival difference. However, the risk of de novo hepatitis B virus infection was significantly increased in HBsAb- and HBcAb-negative recipients. All patients were successfully treated even after recurrence. PMID- 26366385 TI - Meconium-related ileus in very low birth weight and extremely low birth weight infants: immediate and one-year postoperative outcomes. AB - PURPOSE: One of the major causes of bowel obstruction in extremely premature infants is a meconium obstruction. However, there are many challenges not only in the recognition and diagnosis, but also in the management of meconium obstruction. This study aimed to find perioperative clinical features and determine the postoperative course of meconium-related ileus in very low birth weight (VLBW) and extremely low birth weight (ELBW) infants. METHODS: We retrospectively reviewed the clinical data of premature infants (n = 11, VLBW infnats; n = 16, ELBW infants) with a meconium-related ileus who underwent operation for intractable ileus between January 2009 and May 2013. RESULTS: The average duration of conservative management was longer and postnatal age was older in ELBW infants than VLBW infants: 19.9 days vs. 11.5 days and 34.9 days vs. 19.2 days. The immediate postoperative course (day that beginning feeding and full feeding) was not significantly different based on birth weight, but the ELBW infants had slightly higher mortality. At 12 months of corrected age after operation, both average body weight and average height was below 10th percentile for growth in most infants (61.1%). CONCLUSION: There was a slightly high mortality in the ELBW infants, but two groups did not experience significant differences in the immediate postoperative course of meconium-related ileus. Nevertheless, considering their growth patterns, it is necessary to do a close follow-up and more aggressive nutritional management to achieve optimal growth and development in both patient groups. PMID- 26366386 TI - Acute appendicitis caused by foreign body ingestion. AB - Foreign bodies usually do not cause complications and pass through the gastrointestinal tract spontaneously. Usually endoscopic intervention is recommended within 24 hours. Cases of acute appendicitis caused by foreign bodies are very rare. In our case, we experienced successful endoscopic and surgical treatment of a patient with ingestion of razor blade and some unrecognizable foreign bodies. A 22-year-old soldier was admitted with a small quantity of hematemesis and epigastric pain. We performed emergent endoscopy and successfully removed several foreign bodies. After 17 days, we performed appendectomy to remove the remaining foreign body and to relieve the symptoms. There is no doubt that endoscopic intervention is definitely useful method to remove foreign bodies. If there is no spontaneous drainage of the foreign body from the appendix, an appendectomy must be considered to remove the foreign body and prevent surgical complications such as appendicitis, periappendiceal abscess, and perforation. PMID- 26366387 TI - Multiple visceral artery aneurysms managed by Yasargil aneurysm clips. AB - Here, we present the case of a 37-year-old woman with multiple visceral artery aneurysms in the pancreaticoduodenal, inferior pancreatic and splenic arteries associated with celiac trunk stenosis. An aneurysmectomy and end-to-end anastomosis was performed for two adjacent aneurysms, while clipping with intracranial aneurysm clips were performed for the other three aneurysms. During 36-month follow-up, no recurrence or newly developed lesions were noted, and the celiac artery had been reconstituted spontaneously. We believe that using intracranial aneurysm clips in the treatment of visceral artery aneurysms is feasible and safe and can be considered when endovascular procedures are unlikely to be successful. PMID- 26366388 TI - Various autogenous fresh demineralized tooth forms for alveolar socket preservation in anterior tooth extraction sites: a series of 4 cases. AB - The aim of this study was to evaluate the clinical relevance of autogenous fresh demineralized tooth (Auto-FDT) prepared at chairside immediately after extraction for socket preservation. Teeth were processed to graft materials in block, chip, or powder types immediately after extraction. Extraction sockets were filled with these materials and dental implants were installed immediately or after a delay. A panoramic radiograph and a conebeam CT were taken. In two cases, tissue samples were taken for histologic examination. Vertical and horizontal maintenance of alveolar sockets showed some variance depending on the Auto-FDT and barrier membrane types used. Radiographs showed good bony healing. Histologic sections showed that it guided good new bone formation and resorption pattern of the Auto FDT. This case series shows that Auto-FDT prepared at chairside could be a good material for the preservation of extraction sockets. This study will suggest the possibility of recycling autogenous tooth after immediate extraction. PMID- 26366389 TI - Additional data in the debate on stage I non-small cell lung cancer: surgery versus stereotactic ablative radiotherapy. AB - Lobectomy has been the standard of care for patients with early stage non-small cell lung cancer (NSCLC), resulting in nearly universal local control and excellent overall survival. However, up to one-quarter of early stage patients are unable to undergo or refuse definitive resection. With the increasing adoption of stereotactic ablative radiotherapy (SABR) over conventionally fractionated radiotherapy among medical inoperable patients, tumor control and overall survival rates in this population have significantly improved. Trials demonstrating excellent outcomes among both medically inoperable and medical operable patients with stage I NSCLC have spurred interest in comparisons between surgery and SABR. The recent publication of the randomized STARS and ROSEL trials demonstrated fewer toxicities and an improvement in overall survival among patients treated with SABR compared with surgery. Based on these trials and retrospective comparisons between the modalities, definitive SABR now more firmly appears to be a viable first-line option for treating patients with operable stage I NSCLC. PMID- 26366390 TI - Please sir, may I have some more? The case against underfeeding. PMID- 26366391 TI - The CRISPR road: from bench to bedside on an RNA-guided path. PMID- 26366392 TI - Editorial on "Cancer and the microbiota" published in Science. PMID- 26366393 TI - Dual antiplatelet therapy for acute minor ischemic stroke or transient ischemic attack. PMID- 26366394 TI - Early dual antiplatelet therapy in stroke: should we take the CHANCE? PMID- 26366395 TI - Ex situ reimplantation technique, in central lung tumors. AB - BACKGROUND: The parenchyma-sparing resection is most often performed in patients with impaired preoperative lung or cardiovascular function who would not be able to tolerate a pneumonectomy. METHODS: Our experience on the ex situ reimplantation procedure and the outcome of patients with lung malignancies, who underwent upper or upper-middle lobectomy, with reimplantation of the lower lobe was reported. RESULTS: We present 9 patients mean age 62.6+16.2 years (7 males/2 females) underwent ex situ reimplantation due to extensive lung tumor of upper lobes. The surgical technique precludes IV heparinization and then radical pneumonectomy. The entire lung was immersed in Ringer's solution (temperature 4 degrees centigrade) and bench surgery was performed. The involved upper (or upper middle) lobes with involved lymph nodes were resected, thus leaving the healthy lower lobe of the lung. Pneumoplegia solution, named "Papworth pneumoplegia", was administered (1,473 mL) through catheterization of the pulmonary artery and vein stumps (ante grade and retrograde) along with 250 mL of prostaglandin E1. Re implantation of the lower lobe was performed (I) on the right side, implantation involved the anastomosis of lower pulmonary vein in the site of the cuff of left atrium, followed by suturing the stump of the intermedius pulmonary artery to the right main pulmonary artery and finally the bronchial stumps-intermedius bronchus to the right main bronchus; (II) on the left side the pulmonary vein was anastomosed first, followed by the bronchial stumps and finally by the pulmonary artery. The graft ischemia time was 70.2+8.4 minutes ranged between 55 and 80 minutes. CONCLUSIONS: Re-implantation or auto-transplantation should be considered as a safe option for the appropriate patient with lung cancer. The ex situ separation of the cancerous lobes is technically feasible and allows extensive pulmonary resection while minimizing the loss of pulmonary reserve. Based on our work, the major factors that play a role for the survival of initially resected and then re-implanted lung graft, are: (I) the ischemia time of the re-implanted lobe; (II) the proper use of pneumoplegia solutions, along with prostaglandin E1 and heparin; (III) the occurrence of pulmonary vein thrombosis; and (IV) the bronchial anastomosis. PMID- 26366396 TI - Percutaneously assisted total hip (PATH) and Supercapsular percutaneously assisted total hip (SuperPATH) arthroplasty: learning curves and early outcomes. AB - BACKGROUND: A new family of micro-posterior approaches, percutaneously assisted total hip (PATH), SuperCapsular (SuperCap) and Supercapsular percutaneously assisted total hip (SuperPATH) allow preservation of the short external rotators. This study assesses early outcomes and learning curves of the PATH and SuperPATH approaches. METHODS: Early outcomes of the first consecutive 49 PATH and 50 SuperPATH cases performed by a non-developer surgeon were evaluated. Analysis of variance (ANOVA) was used to compare age, body mass index (BMI), and pre operative hemoglobin. Gender was compared using a Chi-square test. Clinical outcomes were compared using a nonparametric Wilcoxon test or a Chi-square test. Learning curves were assessed using operative time as a surrogate. Acetabular cup abduction and anteversion were compared using the first post-operative radiograph and a modified protractor. RESULTS: Both cohorts were similar with respect to diagnosis, gender, and BMI. Mean operative time in minutes was recorded for the PATH (114.5+/-17.5) and SuperPATH (101.7+/-18.3) cohorts (P value =0.0002). PATH operative time reached a plateau by case 40, but SuperPATH operative time continued to decrease by case 50. Transfusion rates were low in the PATH (4%) and SuperPATH (6%) cohorts. Mean length of stay (LOS) in days for the SuperPATH and PATH cohorts were 2.2 and 3.0, respectively (P value <0.0001). Complication rates were low in the SuperPATH (4.0%) and PATH (4.1%) cohorts. Acetabular cups in the SuperPATH cohort (anteversion: 23.5 degrees +/-8.2 degrees , abduction: 39.0 degrees +/-8.4 degrees ) were significantly more anteverted (P value <0.0001) and less abducted (P value <0.05) than in the PATH cohort (anteversion: 13.1 degrees +/-7.1 degrees ; abduction: 42.9 degrees +/-7.6 degrees ). CONCLUSIONS: Early results demonstrate that the PATH and SuperPATH approaches can be adopted with minimal complications and outcomes consistent with innovator outcomes, even during the learning curve. The SuperPATH technique was associated with shorter operative time that continued to decrease, suggesting that proficiency continues to decrease beyond the first 50 cases. In this author's experience, acetabular cups implanted using the SuperPATH technique were more anteverted than those implanted using the PATH technique. Greater use of the transverse acetabular ligament to guide cup alignment reduced this effect. PMID- 26366397 TI - Supercapsular percutaneously-assisted total hip arthroplasty: radiographic outcomes and surgical technique. AB - BACKGROUND: The supercapsular percutaneously-assisted total hip (SuperPATH((r))) approach for total hip arthroplasty (THA) was developed to promote early mobilization and greater range of motion, physiologic gait kinematics and improved pain control. The superpath approach is a hybrid of the Superior Capsulotomy (SuperCap((r))) approach and the percutaneously assisted total hip (PATH((r))) technique. METHODS: Postoperative radiographs of 66 consecutive patients from the first 100 patients who underwent the SuperPATH approach were analysed by an independent third party for component position and seating, femoral offset and leg length. A detailed description of preoperative and postoperative preparation, soft tissue dissection, preparation of the femoral canal and acetabulum, and implant positioning is also provided with figures to illustrate. RESULTS: All components in this case series were well seated and position deemed optimal. Leg lengths were measured to within 5 mm of the contralateral side and mean acetabular abduction angle was 40.13 degrees (SD 6.30 degrees ). CONCLUSIONS: Through preservation of the external rotators, hip capsule, and abductor integrity, the SuperPATH approach for THA maximally preserves the surrounding soft tissue envelope. Implant position was optimal within the 'learning curve' of the first 100 cases for described THA safe zones. Long term outcome data for the SuperPATH approach are being collected as part of an ongoing study to compare to favourable short and mid-term results. PMID- 26366398 TI - MET deregulation in breast cancer. AB - BACKGROUND: Mesenchymal-epithelial transition (MET) is an oncogene encoding for a trans-membrane tyrosine kinase receptor activated by the hepatocyte growth factor (HGF). MET has a normal function in organ development during embryogenesis and in tissue homeostasis during adult life. Deregulation of HGF/MET signaling pathway is frequently observed in many cancer types, conferring invasive growth and tendency to progression. MET deregulation is due to gene amplification or increased copy number, gene mutation, receptor over-expression or ligand autocrine loops activation. These events lead to migration, invasion, proliferation, metastatic spread and neo-angiogenesis of cancer cells, suggesting that anti-HGF/MET agents may represent a potential antitumor strategy. In breast cancer (BC), preclinical and clinical data demonstrated the role of HGF/MET signalling pathway in carcinogenesis, disease progression and resistance features. METHODS: For this review article, all published data on HGF/MET in BC were collected and analyzed. RESULTS: Several evidences underline that, in early BC, MET over-expression has an independent negative prognostic significance, regardless of method used for evaluation and BC subtypes. Available data suggest that MET is a relevant target particularly in basal-like (BL) and in triple negative BC. Moreover, preclinical and retrospective data support the critical role of MET deregulation in the development of resistance to target-agents, such as anti-HER2 strategies. CONCLUSIONS: MET is a promising new target in BC. Several anti-MET agents are under investigation and ongoing clinical trials will clarify its relevance in BC treatment. PMID- 26366399 TI - Advances in the diagnosis, treatment and prognosis of malignant pleural mesothelioma. AB - Malignant pleural mesothelioma (MPM) is a rare cancer originated from pleural mesothelial cells. MPM has been associated with long-term exposure to asbestos. The prognosis of MPM is poor due to the difficulty of making diagnosis in the early stage, the rapid progression, the high invasiveness and the lack of effective treatment. Although the incidence of MPM is low in China to date, it has a tendency to increase in the coming years. The variety of clinical features may cause the delay of diagnosis and high rate of misdiagnosis. The diagnosis of MPM is based on biopsy of the pleura and immunohistochemistry. As China has become the largest country in the consumption of asbestos, it would give rise to a new surge of MPM in the future. The current treatment of MPM is multimodality therapy including surgery, radiotherapy, chemotherapy and immunotherapy. Two surgical procedures are commonly applied: extrapleural pneumonectomy (EPP) and pleurectomy/decortication (P/D). Three dimensional conformal radiotherapy is used to denote a spectrum of radiation planning and delivery techniques that rely on the 3D imaging to define the tumor. Cisplatin combined with pemetrexed (PEM) is the first-line chemotherapy for MPM. The principal targets in immunotherapy include T cells (Treg), CTLA-4 and PD-1. The diagnosis, treatment and prognosis still remain a major challenge for clinical research and will do so for years to come. PMID- 26366400 TI - Lung abscess-etiology, diagnostic and treatment options. AB - Lung abscess is a type of liquefactive necrosis of the lung tissue and formation of cavities (more than 2 cm) containing necrotic debris or fluid caused by microbial infection. It can be caused by aspiration, which may occur during altered consciousness and it usually causes a pus-filled cavity. Moreover, alcoholism is the most common condition predisposing to lung abscesses. Lung abscess is considered primary (60%) when it results from existing lung parenchymal process and is termed secondary when it complicates another process, e.g., vascular emboli or follows rupture of extrapulmonary abscess into lung. There are several imaging techniques which can identify the material inside the thorax such as computerized tomography (CT) scan of the thorax and ultrasound of the thorax. Broad spectrum antibiotic to cover mixed flora is the mainstay of treatment. Pulmonary physiotherapy and postural drainage are also important. Surgical procedures are required in selective patients for drainage or pulmonary resection. In the current review we will present all current information from diagnosis to treatment. PMID- 26366402 TI - Robotic-assisted left upper lobectomy. PMID- 26366403 TI - Robotic-assisted left upper lingual segmentectomy. PMID- 26366401 TI - Paradigms lost-an emerging role for over-expression of tight junction adhesion proteins in cancer pathogenesis. AB - Tight junctions (TJ) are multi-protein complexes located at the apicalmost tip of the lateral membrane in polarised epithelial and endothelial cells. Their principal function is in mediating intercellular adhesion and polarity. Accordingly, it has long been a paradigm that loss of TJ proteins and consequent deficits in cell-cell adhesion are required for tumour cell dissemination in the early stages of the invasive/metastatic cascade. However it is becoming increasingly apparent that TJ proteins play important roles in not just adhesion but also intracellular signalling events, activation of which can contribute to, or even drive, tumour progression and metastasis. In this review, we shall therefore highlight cases wherein the gain of TJ proteins has been associated with signals promoting tumour progression. We will also discuss the potential of overexpressed TJ proteins to act as therapeutic targets in cancer treatment. The overall purpose of this review is not to disprove the fact that loss of TJ-based adhesion contributes to the progression of several cancers, but rather to introduce the growing body of evidence that gain of TJ proteins may have adhesion independent consequences for promoting progression in other cancers. PMID- 26366404 TI - Sixty shades of oxygen-an attractive opportunity for cancer immunotherapy. PMID- 26366405 TI - Picking a bone with heterotopic ossification: translational progress current and future. PMID- 26366406 TI - Change in Motor and Nonmotor Symptoms Severity in a "Real-Life" Cohort of Subjects with Parkinson's Disease. AB - Background. Parkinson's disease (PD) is a chronic and progressive disorder. Rates of change in motor symptoms have been more studied compared to nonmotor symptoms. The objective was to describe these changes in a real-life cohort of subjects with PD. Methods. A cohort study was carried out from 2011 to 2013. Consecutive patients with PD were recruited from a movement disorders clinic. MDS-UPDRS, PDQ 8, and NMSS were applied to all subjects at an initial evaluation and a subsequent visit (21 +/- 3 months). Disease severity was categorized using a recent classification of MDS-UPDRS severity. Results. The MDS-UPDRS Part III showed a significant decrease of 7.2 +/- 2.31 points (p = 0.001) between evaluations. A mean increase of 0.9 +/- 0.6 points (p = 0.015) in the MDS-UPDRS Part IV was observed. An increase of 14.3 +/- 11.4 points (p = 0.043) in the NMSS total score was found; when assessed individually, the difference was statistically significant only for the perceptual problems/hallucinations item. Quality of life remained unchanged. Conclusion. Motor improvement was observed accompanied by an increase in motor complications possibly as a result of treatment optimization. Nonmotor symptoms worsened as a whole. The overall effect in the quality of life was negligible. PMID- 26366407 TI - Comparative Prevalence of Eating Disorders in Obsessive-Compulsive Disorder and Other Anxiety Disorders. AB - Objective. The purpose of this study was to compare the prevalence of comorbid eating disorders in Obsessive-Compulsive Disorder (OCD) and other common anxiety disorders. Method. 179 patients from the same geographical area with a diagnosis of OCD or an anxiety disorder were divided into two groups based on their primary diagnosis. The prevalence of a comorbid eating disorder was calculated in both groups. Results. There was no statistically significant difference in the prevalence of comorbid eating disorders between the OCD and other anxiety disorders group. Conclusions. These results suggest that the prevalence of comorbid eating disorders does not differ in anxiety disorders when compared with OCD. However, in both groups, it remains statistically higher than that of the general population. PMID- 26366408 TI - The Major Prognostic Features of Nuclear Receptor NR5A2 in Infiltrating Ductal Breast Carcinomas. AB - Background. Gene expression profiles of 181 breast cancer samples were analyzed to identify prognostic features of nuclear receptors NR5A1 and NR5A2 based upon their associated transcriptional networks. Methods. A supervised network analysis approach was used to build the NR5A-mediated transcriptional regulatory network. Other bioinformatic tools and statistical methods were utilized to confirm and extend results from the network analysis methodology. Results. NR5A2 expression is a negative factor in breast cancer prognosis in both ER(-) and ER(-)/ER(+) mixed cohorts. The clinical and cohort significance of NR5A2-mediated transcriptional activities indicates that it may have a significant role in attenuating grade development and cancer related signal transduction pathways. NR5A2 signature that conditions poor prognosis was identified based upon results from 15 distinct probes. Alternatively, the expression of NR5A1 predicts favorable prognosis when concurrent NR5A2 expression is low. A favorable signature of eight transcription factors mediated by NR5A1 was also identified. Conclusions. Correlation of poor prognosis and NR5A2 activity is identified by NR5A2-mediated 15-gene signature. NR5A2 may be a potential drug target for treating a subset of breast cancer tumors across breast cancer subtypes, especially ER(-) breast tumors. The favorable prognostic feature of NR5A1 is predicted by NR5A1-mediated 8-gene signature. PMID- 26366409 TI - Aberrant Gene Regulation in Obstetric, Gynecologic, and Reproductive Diseases. PMID- 26366410 TI - Current Concept and Update of the Macrophage Plasticity Concept: Intracellular Mechanisms of Reprogramming and M3 Macrophage "Switch" Phenotype. AB - Macrophages play a key role in immunity. In this review, we consider the traditional notion of macrophage plasticity, data that do not fit into existing concepts, and a hypothesis for existence of a new switch macrophage phenotype. Depending on the microenvironment, macrophages can reprogram their phenotype toward the proinflammatory M1 phenotype or toward the anti-inflammatory M2 phenotype. Macrophage reprogramming involves well-coordinated changes in activities of signalling and posttranslational mechanisms. Macrophage reprogramming is provided by JNK-, PI3K/Akt-, Notch-, JAK/STAT-, TGF-beta-, TLR/NF-kappaB-, and hypoxia-dependent pathways. Posttranscriptional regulation is based on micro-mRNA. We have hypothesized that, in addition to the M1 and M2 phenotypes, an M3 switch phenotype exists. This switch phenotype responds to proinflammatory stimuli with reprogramming towards the anti-inflammatory M2 phenotype or, contrarily, it responds to anti-inflammatory stimuli with reprogramming towards the proinflammatory M1 phenotype. We have found signs of such a switch phenotype in lung diseases. Understanding the mechanisms of macrophage reprogramming will assist in the selection of new therapeutic targets for correction of impaired immunity. PMID- 26366411 TI - Applying NGS Data to Find Evolutionary Network Biomarkers from the Early and Late Stages of Hepatocellular Carcinoma. AB - Hepatocellular carcinoma (HCC) is a major liver tumor (~80%), besides hepatoblastomas, angiosarcomas, and cholangiocarcinomas. In this study, we used a systems biology approach to construct protein-protein interaction networks (PPINs) for early-stage and late-stage liver cancer. By comparing the networks of these two stages, we found that the two networks showed some common mechanisms and some significantly different mechanisms. To obtain differential network structures between cancer and noncancer PPINs, we constructed cancer PPIN and noncancer PPIN network structures for the two stages of liver cancer by systems biology method using NGS data from cancer cells and adjacent noncancer cells. Using carcinogenesis relevance values (CRVs), we identified 43 and 80 significant proteins and their PPINs (network markers) for early-stage and late-stage liver cancer. To investigate the evolution of network biomarkers in the carcinogenesis process, a primary pathway analysis showed that common pathways of the early and late stages were those related to ordinary cancer mechanisms. A pathway specific to the early stage was the mismatch repair pathway, while pathways specific to the late stage were the spliceosome pathway, lysine degradation pathway, and progesterone-mediated oocyte maturation pathway. This study provides a new direction for cancer-targeted therapies at different stages. PMID- 26366412 TI - The Absence of N-Acetyl-D-glucosamine Causes Attenuation of Virulence of Candida albicans upon Interaction with Vaginal Epithelial Cells In Vitro. AB - To better understand the molecular events underlying vulvovaginal candidiasis, we established an in vitro system. Immortalized vaginal epithelial cells were infected with live, yeast form C. albicans and C. albicans cultured in the same medium without vaginal epithelial cells were used as control. In both cases a yeast to hyphae transition was robustly induced. Whole transcriptome sequencing was used to identify specific gene expression changes in C. albicans. Numerous genes leading to a yeast to hyphae transition and hyphae specific genes were upregulated in the control hyphae and the hyphae in response to vaginal epithelial cells. Strikingly, the GlcNAc pathway was exclusively triggered by vaginal epithelial cells. Functional analysis in our in vitro system revealed that the GlcNAc biosynthesis is involved in the adherence to, and the ability to kill, vaginal epithelial cells in vitro, thus indicating the key role for this pathway in the virulence of C. albicans upon vulvovaginal candidiasis. PMID- 26366413 TI - Fully Automated Quantification of the Striatal Uptake Ratio of [(99m)Tc]-TRODAT with SPECT Imaging: Evaluation of the Diagnostic Performance in Parkinson's Disease and the Temporal Regression of Striatal Tracer Uptake. AB - PURPOSE: We aimed at improving the existing methods for the fully automatic quantification of striatal uptake of [(99m)Tc]-TRODAT with SPECT imaging. PROCEDURES: A normal [(99m)Tc]-TRODAT template was first formed based on 28 healthy controls. Images from PD patients (n = 365) and nPD subjects (28 healthy controls and 33 essential tremor patients) were spatially normalized to the normal template. We performed an inverse transform on the predefined striatal and reference volumes of interest (VOIs) and applied the transformed VOIs to the original image data to calculate the striatal-to-reference ratio (SRR). The diagnostic performance of the SRR was determined through receiver operating characteristic (ROC) analysis. RESULTS: The SRR measured with our new and automatic method demonstrated excellent diagnostic performance with 92% sensitivity, 90% specificity, 92% accuracy, and an area under the curve (AUC) of 0.94. For the evaluation of the mean SRR and the clinical duration, a quadratic function fit the data with R (2) = 0.84. CONCLUSIONS: We developed and validated a fully automatic method for the quantification of the SRR in a large study sample. This method has an excellent diagnostic performance and exhibits a strong correlation between the mean SRR and the clinical duration in PD patients. PMID- 26366414 TI - Optimization of Fermentation Medium for Extracellular Lipase Production from Aspergillus niger Using Response Surface Methodology. AB - Lipase produced by Aspergillus niger is widely used in various industries. In this study, extracellular lipase production from an industrial producing strain of A. niger was improved by medium optimization. The secondary carbon source, nitrogen source, and lipid were found to be the three most influential factors for lipase production by single-factor experiments. According to the statistical approach, the optimum values of three most influential parameters were determined: 10.5 g/L corn starch, 35.4 g/L soybean meal, and 10.9 g/L soybean oil. Using this optimum medium, the best lipase activity was obtained at 2,171 U/mL, which was 16.4% higher than using the initial medium. All these results confirmed the validity of the model. Furthermore, results of the Box-Behnken Design and quadratic models analysis indicated that the carbon to nitrogen (C/N) ratio significantly influenced the enzyme production, which also suggested that more attention should be paid to the C/N ratio for the optimization of enzyme production. PMID- 26366415 TI - In Vitro and In Vivo Response to Low-Modulus PMMA-Based Bone Cement. AB - The high stiffness of acrylic bone cements has been hypothesized to contribute to the increased number of fractures encountered after vertebroplasty, which has led to the development of low-modulus cements. However, there is no data available on the in vivo biocompatibility of any low-modulus cement. In this study, the in vitro cytotoxicity and in vivo biocompatibility of two types of low-modulus acrylic cements, one modified with castor oil and one with linoleic acid, were evaluated using human osteoblast-like cells and a rodent model, respectively. While the in vitro cytotoxicity appeared somewhat affected by the castor oil and linoleic acid additions, no difference could be found in the in vivo response to these cements in comparison to the base, commercially available cement, in terms of histology and flow cytometry analysis of the presence of immune cells. Furthermore, the in vivo radiopacity of the cements appeared unaltered. While these results are promising, the mechanical behavior of these cements in vivo remains to be investigated. PMID- 26366416 TI - Lysophosphatidic Acid Inhibits Apoptosis Induced by Cisplatin in Cervical Cancer Cells. AB - Cervical cancer is the second most common cause of cancer death in women worldwide. Lysophosphatidic acid (LPA) level has been found significantly increased in the serum of patients with ovarian, cervical, and colon cancers. LPA level in cervical cancer patients is significantly higher than in healthy controls. LPA receptors were found highly expressed in cervical cancer cells, suggesting LPA may play a role in the development of cervical cancer. The aim of this study is to investigate the effect of LPA on the apoptosis induced by cisplatin (DDP) in cervical cancer cell line and the underlying changes in signaling pathways. Our study found that cisplatin induced apoptosis of Hela cell through inhibiting expression of Bcl-2, upregulating the expression of Bax, Fas L, and the enzyme activity of caspase-3 (p < 0.05); LPA significantly provided protection against the apoptosis induced by cisplatin by inhibiting the above alterations in apoptotic factor caused by cisplatin (p < 0.05). Moreover, PI3K/AKT pathway was found to be important for the LPA antiapoptosis effect, and administration of PI3K/AKT partially reversed the LPA-mediated protection against cisplatin-induced apoptosis (p < 0.05). These findings have shed new lights on the LPA bioactivity in cervical cancer cells and pointed to a possible sensitization scheme through combined administration of PI3K inhibitor and cisplatin for better treatment of cervical cancer patients, especially those with elevated LPA levels. PMID- 26366417 TI - Systematic Analysis of Endometrial Cancer-Associated Hub Proteins Based on Text Mining. AB - OBJECTIVE: The aim of this study was to systematically characterize the expression of endometrial cancer- (EC-) associated genes and to analysis the functions, pathways, and networks of EC-associated hub proteins. METHODS: Gene data for EC were extracted from the PubMed (MEDLINE) database using text mining based on NLP. PPI networks and pathways were integrated and obtained from the KEGG and other databases. Proteins that interacted with at least 10 other proteins were identified as the hub proteins of the EC-related genes network. RESULTS: A total of 489 genes were identified as EC-related with P < 0.05, and 32 pathways were identified as significant (P < 0.05, FDR < 0.05). A network of EC related proteins that included 271 interactions was constructed. The 17 proteins that interact with 10 or more other proteins (P < 0.05, FDR < 0.05) were identified as the hub proteins of this PPI network of EC-related genes. These 17 proteins are EGFR, MET, PDGFRB, CCND1, JUN, FGFR2, MYC, PIK3CA, PIK3R1, PIK3R2, KRAS, MAPK3, CTNNB1, RELA, JAK2, AKT1, and AKT2. CONCLUSION: Our data may help to reveal the molecular mechanisms of EC development and provide implications for targeted therapy for EC. However, corrections between certain proteins and EC continue to require additional exploration. PMID- 26366418 TI - Underground Coal Mining: Relationship between Coal Dust Levels and Pneumoconiosis, in Two Regions of Colombia, 2014. AB - In Colombia, coal miner pneumoconiosis is considered a public health problem due to its irreversibility, high cost on diagnosis, and lack of data related to its prevalence in the country. Therefore, a cross-sectional study was carried out in order to determine the prevalence of pneumoconiosis in underground coal mining workers in two regions of Colombia. The results showed a 35.9% prevalence of pneumoconiosis in the study group (42.3% in region 1 and 29.9% in region 2). An association was found between a radiologic diagnosis of pneumoconiosis and a medium risk level of exposure to carbon dust (OR: 2.901, 95% CI: 0.937, 8.982), medium size companies (OR: 2.301, 95% CI: 1.260-4.201), length of mining work greater than 25 years (OR: 3.222, 95% CI: 1.806-5.748), and a history of smoking for more than one year (OR: 1.479, 95% CI: 0.938-2.334). These results establish the need to generate an intervention strategy aimed at preventing the identified factors, as well as a timely identification and effective treatment of pneumoconiosis in coal miners, in which the commitment of the General Health and Social Security System and the workers compensation system is ensured. PMID- 26366419 TI - Profiling of Selected MicroRNAs in Proliferative Eutopic Endometrium of Women with Ovarian Endometriosis. AB - It has been well documented that aberrant expression of selected microRNAs (miRNAs) might contribute to the pathogenesis of disease. The aim of the present study is to compare miRNA expression by the most comprehensive locked-nucleic acid (LNA) miRNA microarray in eutopic endometrium of patients with endometriosis and control. In the study we recruited 21 patients with endometriosis and 25 were disease-free women. The miRNA expression profiles were determined using the LNA miRNA microarray and validated for selected molecules by real-time PCR. We identified 1198 human miRNAs significantly differentially altered in endometriosis versus control samples using false discovery rate of <5%. However only 136 miRNAs showed differential regulation by fold change of at least 1.3. By the use of selected statistical analysis we obtained 45 potential pathways that might play a role in the pathogenesis of endometriosis. We also found that natural killer cell mediated cytotoxicity pathway was found to be inhibited which is consistent with previous studies. There are several pathways that may be potentially dysregulated, due to abnormal miRNA expression, in eutopic endometrium of patients with endometriosis and in this way contribute to its pathogenesis. PMID- 26366420 TI - Participation of WNT and beta-Catenin in Physiological and Pathological Endometrial Changes: Association with Angiogenesis. AB - WNT proteins are involved in embryonic development, sex determination, stem cell recruitment, angiogenesis, and cancer. They take part in morphological changes in the endometrium during development, regulate processes of endometrial proliferation and differentiation. This review presents current knowledge about implication of WNT proteins and beta-catenin in physiological endometrial functions as well as their involvement in uterine carcinogenesis. Influence of WNT proteins on the formation of blood vessel, taking place both under healthy and pathological conditions, is also considered. Participation of WNT proteins, beta-catenin, and inhibitors and inducers of WNT signaling in the process of endometrial angiogenesis is largely unknown. Thus, confirmation of their local and systemic participation in the process of endometrial angiogenesis may in the long term help to establish new diagnostic and therapeutic approaches in conditions associated with the pathology of the female reproductive system. PMID- 26366421 TI - Probiotics (Bifidobacterium longum) Increase Bone Mass Density and Upregulate Sparc and Bmp-2 Genes in Rats with Bone Loss Resulting from Ovariectomy. AB - Probiotics are live microorganisms that exert beneficial effects on the host, when administered in adequate amounts. Mostly, probiotics affect the gastrointestinal (GI) tract of the host and alter the composition of gut microbiota. Nowadays, the incidence of hip fractures due to osteoporosis is increasing worldwide. Ovariectomized (OVX) rats have fragile bone due to estrogen deficiency and mimic the menopausal conditions in women. Therefore, this study aimed to examine the effects of Bifidobacterium longum (B. longum) on bone mass density (BMD), bone mineral content (BMC), bone remodeling, bone structure, and gene expression in OVX rats. The rats were randomly assigned into 3 groups (sham, OVX, and the OVX group supplemented with 1 mL of B. longum 10(8)-10(9) colony forming units (CFU)/mL). B. longum was given once daily for 16 weeks, starting from 2 weeks after the surgery. The B. longum supplementation increased (p < 0.05) serum osteocalcin (OC) and osteoblasts, bone formation parameters, and decreased serum C-terminal telopeptide (CTX) and osteoclasts, bone resorption parameters. It also altered the microstructure of the femur. Consequently, it increased BMD by increasing (p < 0.05) the expression of Sparc and Bmp-2 genes. B. longum alleviated bone loss in OVX rats and enhanced BMD by decreasing bone resorption and increasing bone formation. PMID- 26366422 TI - A Novel Foam Contrast Agent Suitable for Fluoroscopic Interventional Procedure: Comparative Study of Physical Properties and Experimental Intervention in Animal Model. AB - In fluoroscopic contrast study for interventional procedure, liquid contrast agent may be diluted in body fluid, losing its contrast effect. We developed a novel contrast agent of "foam state" to maintain contrast effect for enough time and performed a comparative study of physical properties and its usefulness in experimental intervention in animal model. The mean size of microbubble of foam contrast was 13.8 +/- 3.6 um. The viscosity was 201.0 +/- 0.624 cP (centipoise) and the specific gravity was 0.616. The foam decayed slowly and it had 97.5 minutes of half-life. In terms of the sustainability in a slow flow environment, foam contrast washed out much more slowly than a conventional contrast. In experimental colonic stent placement, foam contrast revealed significantly better results than conventional contrast in procedure time, total amount of contrast usage, and the number of injections (p < 0.05). Our foam contrast has high viscosity and low specific gravity and maintains foam state for a sufficient time. Foam contrast with these properties was useful in experimental intervention in animal model. We anticipate that foam contrast may be applied to various kinds of interventional procedures. PMID- 26366423 TI - Collagen Metabolism Biomarkers and Health Related Quality of Life in Pulmonary Arterial Hypertension. AB - OBJECTIVES: The goal of this study was to investigate the association between collagen metabolism biomarkers and health related quality of life (HRQoL) in PAH patients. METHODS: We prospectively enrolled 68 stable idiopathic, anorexigen associated, and hereditary PAH subjects and 37 healthy controls. Serum samples were analyzed for N-terminal propeptide of type III procollagen (PIIINP), c terminal telopeptide of collagen type I (CITP), matrix metalloproteinase 9 (MMP 9) and tissue inhibitor of metalloproteinase 1 (TIMP-1). The Minnesota Living with Heart Failure (MLWHF), Euro QoL-5D (EQ-5D), Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) and Short Form (SF-36) general health survey were administered at the time of blood draw. General linear models, as well as logistic regression models were used to assess associations between variables. RESULTS: CITP, PIIINP, MMP9, and TIMP1 levels, and all HRQoL domains were significantly different between controls and PAH patients (p<0.001 for each). Interestingly, PIIINP levels were significantly associated with MLWHF physical (coef=1.63, and p=0.02), SF-36 physical (coef=-2.93, p=0.004), and EQ-5D aggregate (coef=0.34, p=0.001) scores. Several of the CAMPHOR scores strongly linearly associated with PIIINP. The odds of obtaining a walk distance >=330 meters decrease by 38% per unit increase in PIIINP (OR=0.62; 95% CI=0.43, 0.90) and a PIIINP cutoff of 5.53 MUg/L provided 81% sensitivity and 82% specificity. CONCLUSIONS: PIIINP is a good predictor of disease severity, and is strongly related to HRQoL scores in PAH patients. These relationships suggest PIIINP as a promising tool for PAH clinicians to determine or confirm the level of disease severity. PMID- 26366424 TI - Generation of axolotl hematopoietic chimeras. AB - Wound repair is an extremely complex process that requires precise coordination between various cell types including immune cells. Unfortunately, in mammals this usually results in scar formation instead of restoration of the original fully functional tissue, otherwise known as regeneration. Various animal models like frogs and salamanders are currently being studied to determine the intracellular and intercellular pathways, controlled by gene expression, that elicit cell proliferation, differentiation, and migration of cells during regenerative healing. Now, the necessary genetic tools to map regenerative pathways are becoming available for the axolotl salamander, thus allowing comparative studies between scarring and regeneration. Here, we describe in detail three methods to produce axolotl hematopoietic cell-tagged chimeras for the study of hematopoiesis and regeneration. PMID- 26366425 TI - The Potential to Promote Resilience: Piloting a Minority Stress-Informed, GSA Based, Mental Health Promotion Program for LGBTQ Youth. AB - This article describes the results of a pilot study to determine the feasibility and acceptability of a mental health promotion program that was developed to address minority stressors and promote coping skills among lesbian, gay, bisexual, transgender, and queer (LGBTQ) youth. It was hypothesized that the program would be feasible to implement within the context of a gay-straight alliance (GSA) and that GSA members would find the program acceptable (e.g., educational, enjoyable, helpful, and relevant). Participants included ten members of a high school GSA in the northeastern United States. The program sessions were delivered during GSA meetings. The first session emphasized the identification of minority and general stressors, which was followed by a discussion of coping strategies. The remaining sessions emphasized the development of cognitive coping, affect regulation, and problem-solving skills. After each session, participants completed a 13-item feedback form. Ten items assessed acceptability and three open-ended items allowed participants to provide constructive feedback. Although the program was feasible to implement within the GSA setting, attendance at the sessions was variable. Those who attended the sessions reported them to be enjoyable, informative, relevant to their lives, and potentially helpful for other LGBTQ students. After revising the program, future research is needed to investigate its dissemination potential and determine whether the program can disrupt the minority stress-psychiatric distress relationship. PMID- 26366426 TI - Hepatic insulin gene therapy prevents diabetic enteropathy in STZ-treated CD-1 mice. AB - Depending on the population examined, from 6 to 83% of people with diabetes mellitus exhibit symptoms of altered gut motility, manifesting as dysphagia, reflux, early satiety, nausea, abdominal pain, diarrhea, or constipation. Hyperglycemia-induced cell loss within the enteric nervous system has been demonstrated in both diabetic rodents and patients with diabetes. Glycemic control is recommended to prevent diabetic gastroenteropathy but is often difficult to achieve with current treatment modalities. We asked if hepatic insulin gene therapy (HIGT) could inhibit the development of diabetic gastroenteropathy in mice. Bowel length, bowel transit, colonic muscle relaxation, and the numbers of both stimulatory and inhibitory neurons in the colonic myenteric plexus were compared in groups of diabetic mice (DM), control nondiabetic mice (Con), and diabetic mice treated with HIGT (HIGT). Delivery of a metabolically responsive insulin transgene to the liver of STZ-diabetic mice with an adeno-associated virus, sero-type 8 (AAV8) produced near-normal blood sugars for over 1 month and prevented anatomic, functional, and neurohistologic changes observed in diabetic mice. We conclude that in addition to normalizing oxidative metabolism in diabetic rodents, HIGT is sufficient to prevent the development of diabetic gastroenteropathy. PMID- 26366427 TI - Measuring Outcome in the Treatment of Cocaine Dependence. AB - BACKGROUND: Little in known about the extent to which outcome measures used in studies of the treatment of cocaine dependence are associated with longer-term use and with broader measures of clinical improvement. The current study examined reductions in use, and abstinence-oriented measures, in relation to functioning and longer-term clinical benefits in the treatment of cocaine dependence. METHODS: Overall drug use, cocaine use, and functioning in a number of addiction related domains for 487 patients diagnosed with DSM-IV cocaine dependence and treated with one of four psychosocial interventions in the NIDA Cocaine Collaborative Treatment Study were assessed monthly during 6 months of treatment and at 9, 12, 15, and 18 month follow-up. RESULTS: Measures of during-treatment reduction in use were moderately correlated with drug and cocaine use measures 12 months, but showed non-significant or small correlations with measures of functioning at 12 months. Highest correlations were evident for abstinence measures (maximum consecutive days abstinence and completely abstinent) during treatment in relation to sustained (3 month) abstinence at 12 months. Latent class analysis of patterns of change over time revealed that most patients initially (months 1 to 4 of treatment) either became abstinent immediately or continued to use every month. Over the couse of follow-up, patients either maintained abstinence or used regularly - intermittent use was less common. CONCLUSIONS: There were generally small associations between various measures of cocaine use and longer-term clinical benefits, other than abstinence was associated with continued abstinence. No one method of measuring outcome of treatment of cocaine dependence appears superior to others. PMID- 26366428 TI - Ketamine - A Multifaceted Drug. AB - There is a petition for tight control of ketamine from the Chinese government to classify ketamine as a Schedule I drug, which is defined as a drug with no currently accepted medical use but a high potential for abuse. However, ketamine has unique properties that can benefit different patient populations. Scholars from the Translational Perioperative and Pain Medicine and the International Chinese Academy of Anesthesiology WeChat groups had an interactive discussion on ketamine, including its current medical applications, future research priorities, and benefits versus risks. The discussion is summarized in this manuscript with some minor edits. PMID- 26366429 TI - Recent Developments in the Study of Social Relationships, Stress Responses, and Physical Health. AB - This selective review aims to highlight some of the most recent empirical or theoretical advancements in the study of social relationships as buffers against stress and as protective factors against risk for disease, focusing on articles published between 2013 and 2015. The review summarizes novel findings showing that social relationships can protect individuals against negative health outcomes associated with chronic adversity and can be associated with reduced cumulative physiological damage (allostatic load). There is also evidence that some relationships can be a source of stress. Additionally, recent findings concerning the psychological and neurobiological mechanisms of action for social support, the developmental patterning of social stress-buffering and recent experimental studies attempting to change relationships to affect health are also reviewed. PMID- 26366431 TI - Efficient Mobility Management Signalling in Network Mobility Supported PMIPV6. AB - Proxy Mobile IPV6 (PMIPV6) is a network based mobility management protocol which supports node's mobility without the contribution from the respective mobile node. PMIPV6 is initially designed to support individual node mobility and it should be enhanced to support mobile network movement. NEMO-BSP is an existing protocol to support network mobility (NEMO) in PMIPV6 network. Due to the underlying differences in basic protocols, NEMO-BSP cannot be directly applied to PMIPV6 network. Mobility management signaling and data structures used for individual node's mobility should be modified to support group nodes' mobility management efficiently. Though a lot of research work is in progress to implement mobile network movement in PMIPV6, it is not yet standardized and each suffers with different shortcomings. This research work proposes modifications in NEMO BSP and PMIPV6 to achieve NEMO support in PMIPV6. It mainly concentrates on optimizing the number and size of mobility signaling exchanged while mobile network or mobile network node changes its access point. PMID- 26366432 TI - Exponential H infinity Synchronization of Chaotic Cryptosystems Using an Improved Genetic Algorithm. AB - This paper presents a systematic design methodology for neural-network- (NN-) based secure communications in multiple time-delay chaotic (MTDC) systems with optimal H infinity performance and cryptography. On the basis of the Improved Genetic Algorithm (IGA), which is demonstrated to have better performance than that of a traditional GA, a model-based fuzzy controller is then synthesized to stabilize the MTDC systems. A fuzzy controller is synthesized to not only realize the exponential synchronization, but also achieve optimal H infinity performance by minimizing the disturbance attenuation level. Furthermore, the error of the recovered message is stated by using the n-shift cipher and key. Finally, a numerical example with simulations is given to demonstrate the effectiveness of our approach. PMID- 26366430 TI - A Randomized, Double-Blind, Placebo-Controlled Clinical Trial of a Chemokine Receptor 5 (CCR5) Antagonist to Decrease the Occurrence of Immune Reconstitution Inflammatory Syndrome in HIV-Infection: The CADIRIS Study. AB - BACKGROUND: Immune Reconstitution Inflammatory Syndrome (IRIS) is a common complication of antiretroviral therapy (ART) in HIV-infected patients. IRIS is associated with an increased risk of hospitalization and death. We ascertained whether CCR5 blockade using maraviroc reduces the risk of IRIS. METHODS: The CADIRIS study was a randomized, double-blind, placebo-controlled, clinical trial that accrued subjects from five clinical sites in Mexico and one in South Africa between November 2009 and January 2012, and followed them for one year. The primary outcome was occurrence of IRIS by 24 weeks. HIV-infected adults, naive to ART, with CD4 cells <100/MUL, and HIVRNA >1,000 copies/mL were eligible. We screened 362 subjects; 279 met inclusion criteria, 3 refused participation, and 276 were randomized. Participants received maraviroc 600 mg twice daily or placebo added to an ART regimen that included tenofovir, emtricitabine, and efavirenz for 48 weeks. FINDINGS: There were 276 patients randomized (140 received maraviroc and 136 placebo). There was no difference in the time to IRIS events between treatment arms (HR 1.08, 95% CI (0.66, 1.77), log-rank test p=0.743). In total, 64 (23%) patients had IRIS events, 33 (24%) in the maraviroc arm and 31 (23%) in the placebo arm (p=0.88). INTERPRETATION: Maraviroc had no significant effect on frequency, time or severity of IRIS events after ART initiation. Including a CCR5 inhibitor in an initial treatment regimen does not confer a meaningful protection from the occurrence of IRIS in persons with advanced HIV infection. FUNDING: The trial was funded as investigator initiated research by Pfizer Inc, New York, NY, USA. TRIAL REGISTRATION: ClinicalTrials.gov. ID: NCT00988780 (http://clinicaltrials.gov/ct2/show/NCT00988780). PMID- 26366433 TI - Mental Health of Elementary Schoolteachers in Southern Brazil: Working Conditions and Health Consequences. AB - The mental health of educators is a growing problem in many countries. This study sought to identify self-reported stressful working conditions of elementary schoolteachers and the biopsychosocial consequences of those working conditions and then identify working conditions that promote well-being for teachers in the workplace. Exploratory study was done with 37 teachers. Data collection was performed using a structured interview with a questionnaire. Results show that stressful working conditions are related to inadequate salary, an excessive number of activities, and having to take work home. Biopsychosocial consequences include anxiety, stress, and sleep disorders. There was a statistically significant association between inadequate salary and anxiety (p = 0.01) and between an excessive number of activities and stress (p = 0.01). Teachers reported that a good relationship among colleagues is a working condition that promotes well-being in the workplace. The identification of stressful working conditions for teachers, the biopsychosocial consequences, and working conditions that promote well-being in the workplace are relevant to determining actions that improve the work environment and, consequently, the health of teachers. PMID- 26366434 TI - Pharyngoesophageal Suturing Technique May Decrease the Incidence of Pharyngocutaneous Fistula following Total Laryngectomy. AB - Objectives. A pharyngocutaneous fistula (PCF) following total laryngectomy is associated with increased morbidity and severe life threatening complications. We aimed to review our experience with the PCF following total laryngectomy and determine the impact of previously reported risk factors on the development of PCF in our patients. Methods. The medical records of 20 patients who had a total laryngectomy operation were retrospectively analyzed. The association between the proposed risk factors and the incidence of the PCF was investigated. Results. Comparison of the suture techniques used for the closure of the pharynx (either continuous Cushing type or interrupted) yielded that primary interrupted sutures had a significantly higher incidence of PCF formation (p < 0.05). Although it was not statistically significant, diabetes mellitus was also associated with increased PCF formation (p > 0.05). No significant difference was observed between the PCF and non-PCF groups in terms of other proposed risk factors (p > 0.05). Conclusions. The main risk factor associated with PCF was found to be the type of pharyngeal closure technique. A vertical closure with a Cushing type continuous suture may be more successful than interrupted sutures in preventing a PCF. PMID- 26366435 TI - The Bidirectional Relationship between Metabolism and Immune Responses. AB - Immunometabolism investigates the multiple links between the immune system and metabolism. One main focus of immunometabolism investigates how obesity impacts the immune system and pro-inflammatory immune cell function, leading to metabolic diseases, including type 2 diabetes (T2D). The second focus stresses the metabolic changes that dictate immune cell activation. Several groups have studied these two arms of the field individually, but work that integrates both topics will be required to develop an accurate understanding of how immune cells and metabolic pathways collaborate in obesity and obesity-associated T2D. Investigations of the relationships among obesity-induced changes in the nutritional environment, immune cell activation, and immune cell metabolism may lead to novel and efficacious therapies for obesity-associated disorders such as insulin resistance (IR) and T2D. This review outlines recent insights into two related processes: 1. the role that energy utilization plays in immune responses and 2. the immune cell functions that drive obesity and T2D. Herein, we begin to consider how shifts in available fuel sources in obesity and T2D impact the immune response to both pathogens and chronic over nutrition. PMID- 26366436 TI - Foreword. PMID- 26366438 TI - Hydrogel-Coated Near Infrared Absorbing Nanoshells as Light-Responsive Drug Delivery Vehicles. AB - Nanoparticle drug delivery carriers that can modulate drug release based on an exogenous signal, such as light, are of great interest, especially for improving cancer therapy. A light-activated delivery vehicle was fabricated by synthesizing a thin, thermally responsive poly(N-isopropylacrylamide-co-acrylamide) hydrogel coating directly onto the surfaces of individual near-infrared (NIR) absorbing gold-silica nanoshells. This hydrogel was designed to be in a swollen state under physiological conditions and expel large amounts of water, along with any entrapped drug, at elevated temperatures. The required temperature change can be achieved via NIR absorption by the nanoshell, allowing the hydrogel phase change to be triggered by light, which was observed by monitoring changes in particle sizes as water was expelled from the hydrogel network. The phase change was reversible and repeatable. As a model drug, the chemotherapeutic doxorubicin was loaded into this delivery vehicle, and rapid release of doxorubicin occurred upon NIR exposure. Further, colon carcinoma cells exposed to the irradiated platform displayed nearly 3 times as much doxorubicin uptake as cells exposed to nonirradiated particles or free drug, which in turn resulted in a higher loss of cell viability. We hypothesize these effects are because the NIR-mediated heating results in a transient increase in cell membrane permeability, thus aiding in cellular uptake of the drug. PMID- 26366437 TI - Brain Uptake of Neurotherapeutics after Intranasal versus Intraperitoneal Delivery in Mice. AB - There is a growing global prevalence of neurodegenerative diseases such as Alzheimer's disease and dementia. Current treatment for neurodegenerative diseases is limited due to the blood brain barrier's ability to restrict the entry of therapeutics to the brain. In that context, direct delivery of drugs from nose to brain has gained emerging interest as an important alternative to oral and parenteral routes of administration. Although there are considerable reports showing promising results after intranasal drug delivery in various disease-models and investigatory human clinical trials, there are very few studies showing a detailed pharmacokinetics with regard to the uptake and retention of intranasally delivered material(s) within specific brain regions, which are critical determining factors for dosing conditions and optimal treatment regimen. This investigation compared a time-dependent brain uptake and resident time of various radiolabeled candidate neurotherapeutics after a single bolus intranasal or intraperitoneal administration in mice. Results indicate that the brain uptake of intranasally delivered therapeutic(s) is > 5 times greater than that after intraperitoneal delivery. The peak uptake and resident time of all intranasally delivered test therapeutics for all brain regions is observed to be between 30min-12h, depending upon the distance of brain region from the site of administration, followed by gradual fading of radioactive counts by 24h post intranasal administration. Current study confirms the usefulness of intranasal administration as a non- invasive and efficient means of delivering therapeutics to the brain to treat neurodegenerative diseases including Alzheimer's disease. PMID- 26366439 TI - Molecular overlap in the regulation of SK channels by small molecules and phosphoinositides. AB - Phosphatidylinositol 4,5-bisphosphate (PIP2) directly interacts with the small conductance Ca2+-activated K+ 2-a (SK2-a) channel/calmodulin complex, serving as a critical element in the regulation of channel activity. We report that changes of protein conformation in close proximity to the PIP2 binding site induced by a small-molecule SK channel modulator, NS309, can effectively enhance the interaction between the protein and PIP2 to potentiate channel activity. This novel modulation of PIP2 sensitivity by small-molecule drugs is likely not to be limited in its application to SK channels, representing an intriguing strategy to develop drugs controlling the activity of the large number of PIP2-dependent proteins. PMID- 26366440 TI - Challenges of Fertility Sparing Ovarian Surgery Imposed by Krukenberg Tumors in Pregnancy. AB - Fertility sparing surgery is advocated for reproductive-age women with benign and borderline ovarian tumors. The hormonal milieu of pregnancy may, however, complicate the decision making process. The patient presented in the third trimester with a rapidly growing tumor that was diagnosed as benign steroid cell tumor by intraoperative frozen section. Fertility-sparing surgery with right oophorectomy and partial left oophorectomy was performed. The final pathology examination demonstrated signet cells staining positive for mucin, which is pathognomonic for Krukenberg tumors. Krukenberg cells were overlooked in the frozen section due to the predominance of hormonally active luteinized ovarian stroma cells. This case highlights the challenges associated with fertility sparing surgery in women presenting with ovarian tumors in pregnancy and the limitations of frozen section in providing an accurate diagnosis. PMID- 26366441 TI - Welcome to eNeurologicalSci (eNS)! PMID- 26366442 TI - Radiographic Findings and Clinical Correlates in Pediatric Periorbital Infections. AB - OBJECTIVE: To review radiographic studies of pediatric patients presenting with periorbital infections and to evaluate sinonasal anatomical factors and clinical course related to this disease process. METHODS: Retrospective study review of computed tomography (CT) scans in 100 patients less than 18 years old, admitted to a tertiary children's hospital with the diagnosis of an orbital infection. CT scans were reviewed for anatomic variants and Lund-Mackay scores were calculated. An independent chart reviews of the treatment course and need for surgical intervention was performed. RESULTS: Of 100 patients, 67% were male, 60% had left sided infections, and 30% of patients were treated with surgical drainage. Adenoid hypertrophy (61%), inferior turbinate hypertrophy (80%) and septal deviation (47%) were common, but did not show statistical correlation with the need for surgical intervention. Dehiscence of the lamina papyracea was identified in 21% of patients treated without surgery and in 76% of those requiring surgery (P 0.0048). The average overall Lund-Mackay score was 11.8 and did not correlate with the need for surgical intervention. CONCLUSIONS: To our knowledge, this is the first study to evaluate the incidence of sinonasal anatomic abnormalities in children presenting with periorbital infections. This study also demonstrated that lamina papyracea dehiscence is a common finding and is associated with higher rates of surgical intervention. Such findings may have an important role in the diagnosis, surveillance and management of sinus disease in the pediatric population. PMID- 26366443 TI - Deformability and size-based cancer cell separation using an integrated microfluidic device. AB - Cell sorting by filtration techniques offers a label-free approach for cell separation on the basis of size and deformability. However, filtration is always limited by the unpredictable variation of the filter hydrodynamic resistance due to cell accumulation and clogging in the microstructures. In this study, we present a new integrated microfluidic device for cell separation based on the cell size and deformability by combining the microstructure-constricted filtration and pneumatic microvalves. Using this device, the cell populations sorted by the microstructures can be easily released in real time for subsequent analysis. Moreover, the periodical sort and release of cells greatly avoided cell accumulation and clogging and improved the selectivity. Separation of cancer cells (MCF-7, MDA-MB-231 and MDA231-LM2) with different deformability showed that the mixture of the less flexible cells (MCF-7) and the flexible cells (MDA-MB-231 and MDA231-LM2) can be well separated with more than 75% purity. Moreover, the device can be used to separate cancer cells from the blood samples with more than 90% cell recovery and more than 80% purity. Compared with the current filtration methods, the device provides a new approach for cancer cell separation with high collection recovery and purity, and also, possesses practical potential to be applied as a sample preparation platform for fundamental studies and clinical applications. PMID- 26366444 TI - Preface. PMID- 26366445 TI - Stem cell research for cardiac patients. AB - Clinical cardiologist Professor Anthony Mathur is driving forward stem cell research in the UK for patients suffering heart attacks and heart failure. He spoke to Mark Nicholls about the latest phase of his work. PMID- 26366446 TI - Introducing SNOMED CT to cardiology, from Malaysia. PMID- 26366447 TI - Exercise Metabolism. PMID- 26366448 TI - Response to validation of devices and methods for noninvasive estimation of central aortic blood pressure in children. PMID- 26366449 TI - Finding the positive in the negative. PMID- 26366451 TI - Is CMS penalizing top performers? Study finds good performers more likely to be dinged. PMID- 26366452 TI - CMS finalizes two-midnight rule. PMID- 26366453 TI - Enhanced recovery comes to America. Euro method shows great promise for surgical patients. PMID- 26366454 TI - Looking at the in-between moments of care. New certification from TJC for integrated care. PMID- 26366455 TI - The best catheter is one that's out. Protocol sets first call for removal in OR. PMID- 26366456 TI - Magnet status improves outcomes. Mimic what you can for better patient care. PMID- 26366457 TI - Data from NSQIP better than others. Conference presentations show power of member metrics. PMID- 26366458 TI - Journal outlines issues of contention in HAC program. PMID- 26366459 TI - Intra-Aortic Balloon Pump Malposition Reduces Visceral Artery Perfusion in an Acute Animal Model. AB - Visceral artery perfusion can be potentially affected by intra-aortic balloon pump (IABP) catheters. We utilized an animal model to quantify the acute impact of a low balloon position on mesenteric artery perfusion. In six pigs (78 +/- 7 kg), a 30-cc IABP was placed in the descending aorta in a transfemoral procedure. The celiac artery (CA) and the cranial mesenteric artery (CMA) were surgically dissected. Transit time blood flow was measured for (i) baseline, (ii) 1:1 augmentation with the balloon proximal to the visceral arteries, and (iii) 1:1 augmentation with the balloon covering the visceral arteries. Blood flow in the CMA and CA was reduced by 17 and 24%, respectively, when the balloon compromised visceral arteries compared with a position above the visceral arteries (flow in mL/min: CMA: (i) 1281 +/- 512, (ii) 1389 +/- 287, (iii) 1064 +/- 276, P < 0.05 for 3 vs. 1 and 3 vs. 2; CA: (i) 885 +/- 370, (ii) 819 +/- 297, (iii) 673 +/- 315; P < 0.05 for 3 vs. 1). The covering of visceral arteries by an IABP balloon causes a significant reduction of visceral artery perfusion; thus, the positioning of this device during implantation is critical for obtaining a satisfactory outcome. PMID- 26366460 TI - The flip side of the other-race coin: They all look different to me. AB - Poorer recognition of other-race faces than own-races faces has been attributed to a problem of discrimination (i.e., telling faces apart). The conclusion that 'they all look the same to me' is based on studies measuring the perception/memory of highly controlled stimuli, typically involving only one or two images of each identity. We hypothesized that such studies underestimate the challenge involved in recognizing other-race faces because in the real world, an individual's appearance varies in a number of ways (e.g., lighting, expression, hairstyle), reducing the utility of relying on pictorial cues to identity. In two experiments, Caucasian and East Asian participants completed a perceptual sorting task in which they were asked to sort 40 photographs of two unfamiliar identities into piles such that each pile contained all photographs of a single identity. Participants perceived more identities when sorting other-race faces than own race faces, both when sorting celebrity (Experiment 1) and non-celebrity (Experiment 2) faces, suggesting that in the real world, 'they all look different to me'. We discuss these results in the light of models in which each identity is represented as a region in a multidimensional face space; we argue that this region is smaller for other-race than own-race faces. PMID- 26366461 TI - Discovering Alzheimer Genetic Biomarkers Using Bayesian Networks. AB - Single nucleotide polymorphisms (SNPs) contribute most of the genetic variation to the human genome. SNPs associate with many complex and common diseases like Alzheimer's disease (AD). Discovering SNP biomarkers at different loci can improve early diagnosis and treatment of these diseases. Bayesian network provides a comprehensible and modular framework for representing interactions between genes or single SNPs. Here, different Bayesian network structure learning algorithms have been applied in whole genome sequencing (WGS) data for detecting the causal AD SNPs and gene-SNP interactions. We focused on polymorphisms in the top ten genes associated with AD and identified by genome-wide association (GWA) studies. New SNP biomarkers were observed to be significantly associated with Alzheimer's disease. These SNPs are rs7530069, rs113464261, rs114506298, rs73504429, rs7929589, rs76306710, and rs668134. The obtained results demonstrated the effectiveness of using BN for identifying AD causal SNPs with acceptable accuracy. The results guarantee that the SNP set detected by Markov blanket based methods has a strong association with AD disease and achieves better performance than both naive Bayes and tree augmented naive Bayes. Minimal augmented Markov blanket reaches accuracy of 66.13% and sensitivity of 88.87% versus 61.58% and 59.43% in naive Bayes, respectively. PMID- 26366462 TI - Body composition of female road and track endurance cyclists: Normative values and typical changes. AB - The aims of this study were to describe normative values and seasonal variation of body composition in female cyclists comparing female road and track endurance cyclists, and to validate the use of anthropometry to monitor lean mass changes. Anthropometric profiles (seven site skinfolds) were measured over 16 years from 126 female cyclists. Lean mass index (LMI) was calculated as body weight * skinfolds(-x). The exponent (x) was calculated as the slope of the natural logarithm of body weight and skinfolds. Percentage changes in LMI were compared to lean mass changes measured using dual-energy X-ray absorptiometry (DXA) in a subset of 25 road cyclists. Compared to sub-elite and elite cyclists, world class cyclists were (mean [95% CI]) 1.18 kg [0.46, 1.90] and 0.60 kg [0.05, 1.15] lighter and had skinfolds that were 7.4 mm [3.8, 11.0] and 4.6 mm [1.8, 7.4] lower, respectively. Body weight (0.41 kg [0.04, 0.77]) and skinfolds (4.0 mm [2.1, 6.0]) were higher in the off-season compared to the early-season. World class female road cyclists had lower body weight (6.04 kg [2.73, 9.35]) and skinfolds (11.5 mm [1.1, 21.9]) than track endurance cyclists. LMI (mean exponent 0.15 [0.13, 0.18]) explained 87% of the variance in DXA lean mass. In conclusion, higher performing female cyclists were lighter and leaner than their less successful peers, road cyclists were lighter and leaner than track endurance cyclists, and weight and skinfolds were lowest early in the season. LMI appears to be a reasonably valid tool for monitoring lean mass changes. PMID- 26366464 TI - Nickel-Catalyzed Regioselective Cross-Dehydrogenative Coupling of Inactive C(sp(3))-H Bonds with Indole Derivatives. AB - A nickel-catalyzed regiosepecific C2- versus C3-oxidative cross-coupling reaction of indoles with 1,4-dioxane and other inactive C(sp(3))-H bonds is described. The divergent synthesis of C(sp(3))-C(sp(2)) bonds was achieved in satisfactory yields with di-tert-butyl peroxide (DTBP) as the oxidant, which provides an efficient strategy for the selective construction of cyclic ethers containing heteroaromatic core structures. PMID- 26366465 TI - The content of recurrent dreams in young adolescents. AB - Studies on children's recurrent dreams have been largely anecdotal and based on adults' recollections of dreams experienced during childhood. We collected 102 reports of recurrent dreams from a sample of young adolescents aged between 11 and 15years and scored the narratives using a range of content measures, including in relation to the threat simulation theory (TST) of dreaming. The most frequently reported themes involved confrontations with monsters or animals, followed by physical aggressions, falling and being chased. Recurrent dreams were more likely to include negative content elements than positive elements. Only half of the recurrent dreams contained threatening elements and their analysis provided mixed support for the TST. Differences between the content of recurrent dreams reported by young adolescent versus adults are discussed as are possible sex effects and key issues that remain to be addressed by future research. PMID- 26366466 TI - The inhibitory spillover effect: Controlling the bladder makes better liars. AB - The Inhibitory-Spillover-Effect (ISE) on a deception task was investigated. The ISE occurs when performance in one self-control task facilitates performance in another (simultaneously conducted) self-control task. Deceiving requires increased access to inhibitory control. We hypothesized that inducing liars to control urination urgency (physical inhibition) would facilitate control during deceptive interviews (cognitive inhibition). Participants drank small (low control) or large (high-control) amounts of water. Next, they lied or told the truth to an interviewer. Third-party observers assessed the presence of behavioral cues and made true/lie judgments. In the high-control, but not the low control condition, liars displayed significantly fewer behavioral cues to deception, more behavioral cues signaling truth, and provided longer and more complex accounts than truth-tellers. Accuracy detecting liars in the high-control condition was significantly impaired; observers revealed bias toward perceiving liars as truth-tellers. The ISE can operate in complex behaviors. Acts of deception can be facilitated by covert manipulations of self-control. PMID- 26366468 TI - Maternal hypertension and infant growth. PMID- 26366467 TI - Pharmacological treatment of organophosphorus insecticide poisoning: the old and the (possible) new. AB - Despite being a major clinical and public health problem across the developing world, responsible for at least 5 million deaths over the last three decades, the clinical care of patients with organophosphorus (OP) insecticide poisoning has little improved over the last six decades. We are still using the same two antidotes - atropine and oximes - that first came into clinical use in the late 1950s. Clinical research in South Asia has shown how improved regimens of atropine can prevent deaths. However, we are still unsure about which patients are most likely to benefit from the use of oximes. Supplemental antidotes, such as magnesium, clonidine and sodium bicarbonate, have all been proposed and studied in small trials without production of definitive answers. Novel antidotes such as nicotinic receptor antagonists, beta-adrenergic agonists and lipid emulsions are being studied in large animal models and in pilot clinical trials. Hopefully, one or more of these affordable and already licensed antidotes will find their place in routine clinical care. However, the large number of chemically diverse OP insecticides, the varied poisoning they produce and their varied response to treatment might ultimately make it difficult to determine definitively whether these antidotes are truly effective. In addition, the toxicity of the varied solvents and surfactants formulated with the OP active ingredients complicates both treatment and studies. It is possible that the only effective way to reduce deaths from OP insecticide poisoning will be a steady reduction in their agricultural use worldwide. PMID- 26366469 TI - Enantioselective addition of arylboronic acids to methyl 2-formylbenzoates by using a ruthenium/Me-BIPAM catalyst for synthesis of chiral 3-aryl isobenzofuranones. AB - Ruthenium/Me-BIPAM-catalyzed asymmetric addition of arylboronic acids to methyl 2 formylbenzoates afforded chiral 3-aryl-isobenzofuranones. [RuCl2(p-cymene)]2/Me BIPAM and RuCl2(PPh3)3/Me-BIPAM catalyst systems tolerate a variety of functional groups and give high yields with high enantioselectivities. PMID- 26366470 TI - Comparison of historical medical spending patterns among the BRICS and G7. AB - OBJECTIVE: The past few decades have been marked by a bold increase in national health spending across the globe. Rather successful health reforms in leading emerging markets such as BRICS reveal a reshaping of their medical care-related expenditures. There is a scarcity of evidence explaining differences in long-term medical spending patterns between top ranked G7 traditional welfare economies and the BRICS nations. METHODS: A retrospective observational study was conducted on a longitudinal WHO Global Health Expenditure data-set based on the National Health Accounts (NHA) system. Data were presented in a simple descriptive manner, pointing out health expenditure dynamics and differences between the two country groups (BRICS and G7) and individual nations in a 1995-2013 time horizon. RESULTS: Average total per capita health spending still remains substantially higher among G7 (4747 Purchase Power Parity (PPP) $PPP in 2013) compared to the BRICS (1004 $PPP in 2013) nations. The percentage point share of G7 in global health expenditure (million current PPP international $US) has been falling constantly since 1995 (from 65% in 1995 to 53.2% in 2013), while in BRICS nations it grew (from 10.7% in 1995 to 20.2% in 2013). Chinese national level medical spending exceeded significantly that of all G7 members except the US in terms of current $PPP in 2013. CONCLUSIONS: Within a limited time horizon of only 19 years it appears that the share of global medical spending by the leading emerging markets has been growing steadily. Simultaneously, the world's richest countries' global share has been falling constantly, although it continues to dominate the landscape. If the contemporary global economic mainstream continues, the BRICS per capita will most likely reach or exceed the OECD average in future decades. Rising out-of-pocket expenses threatening affordability of medical care to poor citizens among the BRICS nations and a too low percentage of GDP in India remain the most notable setbacks of these developments. PMID- 26366471 TI - Effect of Lemongrass Aroma on Experimental Anxiety in Humans. AB - OBJECTIVES: The objective of this study was to evaluate the potential anxiolytic effect of lemongrass (Cymbopogon citratus) aroma in healthy volunteers submitted to an anxiogenic situation. DESIGN: Forty male volunteers were allocated to four different groups for the inhalation of lemongrass essential oil (test aroma: three or six drops), tea tree essential oil (control aroma: three drops), or distilled water (nonaromatic control: three drops). Immediately after inhalation, each volunteer was submitted to an experimental model of anxiety, the video monitored version of the Stroop Color-Word Test (SCWT). OUTCOME MEASURES: Psychologic parameters (state anxiety, subjective tension, tranquilization, and sedation) and physiologic parameters (heart rate and gastrocnemius electromyogram activity) were evaluated before the inhalation period and before, during, and after the SCWT. RESULTS: Individuals exposed to the test aroma (three and six drops), unlike the control groups, presented a reduction in state anxiety and subjective tension, immediately after treatment administration. In addition, although they presented an anxious response to the task, they completely recovered from it in 5 min, unlike the control groups. Physiologic alterations along the test were not prevented by any treatment, in the same way as has previously been observed for diazepam. CONCLUSIONS: Although more investigations are necessary to clarify the clinical relevance of lemongrass essential oil as an anxiety treatment, this work shows that very brief exposure to this aroma has some perceived anxiolytic effects. PMID- 26366463 TI - Association of Long Runs of Homozygosity With Alzheimer Disease Among African American Individuals. AB - IMPORTANCE: Mutations in known causal Alzheimer disease (AD) genes account for only 1% to 3% of patients and almost all are dominantly inherited. Recessive inheritance of complex phenotypes can be linked to long (>1-megabase [Mb]) runs of homozygosity (ROHs) detectable by single-nucleotide polymorphism (SNP) arrays. OBJECTIVE: To evaluate the association between ROHs and AD in an African American population known to have a risk for AD up to 3 times higher than white individuals. DESIGN, SETTING, AND PARTICIPANTS: Case-control study of a large African American data set previously genotyped on different genome-wide SNP arrays conducted from December 2013 to January 2015. Global and locus-based ROH measurements were analyzed using raw or imputed genotype data. We studied the raw genotypes from 2 case-control subsets grouped based on SNP array: Alzheimer's Disease Genetics Consortium data set (871 cases and 1620 control individuals) and Chicago Health and Aging Project-Indianapolis Ibadan Dementia Study data set (279 cases and 1367 control individuals). We then examined the entire data set using imputed genotypes from 1917 cases and 3858 control individuals. MAIN OUTCOMES AND MEASURES: The ROHs larger than 1 Mb, 2 Mb, or 3 Mb were investigated separately for global burden evaluation, consensus regions, and gene-based analyses. RESULTS: The African American cohort had a low degree of inbreeding (F ~ 0.006). In the Alzheimer's Disease Genetics Consortium data set, we detected a significantly higher proportion of cases with ROHs greater than 2 Mb (P = .004) or greater than 3 Mb (P = .02), as well as a significant 114-kilobase consensus region on chr4q31.3 (empirical P value 2 = .04; ROHs >2 Mb). In the Chicago Health and Aging Project-Indianapolis Ibadan Dementia Study data set, we identified a significant 202-kilobase consensus region on Chr15q24.1 (empirical P value 2 = .02; ROHs >1 Mb) and a cluster of 13 significant genes on Chr3p21.31 (empirical P value 2 = .03; ROHs >3 Mb). A total of 43 of 49 nominally significant genes common for both data sets also mapped to Chr3p21.31. Analyses of imputed SNP data from the entire data set confirmed the association of AD with global ROH measurements (12.38 ROHs >1 Mb in cases vs 12.11 in controls; 2.986 Mb average size of ROHs >2 Mb in cases vs 2.889 Mb in controls; and 22% of cases with ROHs >3 Mb vs 19% of controls) and a gene-cluster on Chr3p21.31 (empirical P value 2 = .006-.04; ROHs >3 Mb). Also, we detected a significant association between AD and CLDN17 (empirical P value 2 = .01; ROHs >1 Mb), encoding a protein from the Claudin family, members of which were previously suggested as AD biomarkers. CONCLUSIONS AND RELEVANCE: To our knowledge, we discovered the first evidence of increased burden of ROHs among patients with AD from an outbred African American population, which could reflect either the cumulative effect of multiple ROHs to AD or the contribution of specific loci harboring recessive mutations and risk haplotypes in a subset of patients. Sequencing is required to uncover AD variants in these individuals. PMID- 26366472 TI - The identification of malaria in paleopathology-An in-depth assessment of the strategies to detect malaria in ancient remains. AB - The comprehensive analyses of human remains from various places and time periods, either by immunological or molecular approaches, provide circumstantial evidence that malaria tropica haunted humankind at least since dynastic ancient Egypt. Here we summarize the "actual state-of-the-art" of these bio-molecular investigations and offer a solid basis for the discussion of the paleopathology of malaria in human history. PMID- 26366473 TI - Bacterial Synthesis of Unusual Sulfonamide and Sulfone Antibiotics by Flavoenzyme Mediated Sulfur Dioxide Capture. AB - Sulfa drugs, such as sulfonilamide and dapsone, are classical antibiotics that have been in clinical use worldwide. Despite the relatively simple architectures, practically no natural products are known to feature such aromatic sulfonamide or diarylsulfone substructures. We report the unexpected discovery of three fully unprecedented, sulfonyl-bridged alkaloid dimers (sulfadixiamycins A-C) from recombinant Streptomyces species harboring the entire xiamycin biosynthesis gene cluster. Sulfadixiamycins exhibit moderate antimycobacterial activities and potent antibiotic activities even against multidrug-resistant bacteria. Gene inactivation, complementation, and biotransformation experiments revealed that a flavin-dependent enzyme (XiaH) plays a key role in sulfadixiamycin biosynthesis. XiaH mediates a radical-based, three-component reaction involving two equivalents of xiamycin and sulfur dioxide, which is reminiscent of radical styrene/SO2 copolymerization. PMID- 26366475 TI - 9-Valent HPV vaccine for cancers, pre-cancers and genital warts related to HPV. AB - Human papillomavirus (HPV) is the causative agent of nearly all cervical cancer cases as well as a substantial proportion of anal, vulvar, vaginal, penile and oropharyngeal cancers, making it responsible for approximately 5% of the global cancer burden. The first-generation HPV vaccines that is, quadrivalent HPV type 6/11/16/18 vaccine and bivalent HPV type 16/18 vaccine were licensed in 2006 and 2007, respectively. A second-generation 9-valent HPV type 6/11/16/18/31/33/45/52/58 vaccine with broader cancer coverage was initiated even before the first vaccines were approved. By preventing HPV infection and disease due to HPV31/33/45/52/58, the 9vHPV vaccine has the potential to increase prevention of cervical cancer from 70 to 90%. In addition, the 9vHPV vaccine has the potential to prevent 85-95% of HPV-related vulvar, vaginal and anal cancers. Overall, the 9vHPV vaccine addresses a significant unmet medical need, although further health economics and implementation research is needed. PMID- 26366474 TI - Integrating Molecular Testing in the Diagnosis and Management of Children with Thyroid Lesions. AB - Thyroid nodules occur in 1-2% of children, and identifying which nodules are malignant is often challenging. Cytologic evaluation facilitates the diagnosis of thyroid lesions (TLs), but in 10-40% of cases the interpretation is indeterminate. Patients with indeterminate diagnoses are often treated with hemithyroidectomy followed by completion thyroidectomy, if cancer is found in the initial specimen. Exposing patients to multiple surgeries increases costs and morbidity. The American Thyroid Association states that a combination of molecular markers is likely to optimize the management of patients with indeterminate cytology. However, few studies have addressed the molecular alterations present in pediatric TL. Twenty-seven thyroid carcinomas from patients 10 to 19 years of age were tested for alterations common in adult TL, including BRAF V600E mutation, RET fusions, and TERT promoter mutations. Mutation negative cases were subsequently analyzed with a next-generation sequencing (NGS) mutation panel to search for additional targets. Histologic diagnoses included 12 classic papillary thyroid carcinomas (PTCs), 13 follicular variant PTCs, 1 medullary thyroid carcinoma, and 1 follicular carcinoma. Fourteen cases showed lymph node involvement, and 13 cases demonstrated lymphovascular invasion. The BRAF V600E mutation was detected in 10/27 cases, and RET fusions were detected in 6/27 cases. No TERT promoter mutations were identified in any of the cases. The NGS panel revealed additional RET and CTNNB1 pathogenic missense mutations. Our results demonstrate that molecular abnormalities are common in pediatric TLs and suggest that incorporation of molecular testing will be helpful in optimizing patient management. PMID- 26366476 TI - Cognitive-linguistic effort in multidisciplinary stroke rehabilitation: Decreasing vs. increasing cues for word retrieval. AB - Approximately 24% of stroke survivors experience co-occurring aphasia and hemiparesis. These individuals typically attend back-to-back therapy sessions. However, sequentially scheduled therapy may trigger physical and mental fatigue and have an adverse impact on treatment outcomes. The current study tested a hypothesis that exerting less effort during a therapy session would reduce overall fatigue and enhance functional recovery. Two stroke survivors chronically challenged by non-fluent aphasia and right hemiparesis sequentially completed verbal naming and upper-limb tasks on their home computers. The level of cognitive-linguistic effort in speech/language practice was manipulated by presenting verbal naming tasks in two conditions: Decreasing cues (i.e., most-to least support for word retrieval), and Increasing cues (i.e., least-to-most support). The participants completed the same upper-limb exercises throughout the study periods. Both individuals showed a statistically significant advantage of decreasing cues over increasing cues in word retrieval during the practice period, but not at the end of the practice period or thereafter. The participant with moderate aphasia and hemiparesis achieved clinically meaningful gains in upper-limb functions following the decreasing cues condition, but not after the increasing cues condition. Preliminary findings from the current study suggest a positive impact of decreasing cues in the context of multidisciplinary stroke rehabilitation. PMID- 26366477 TI - Methods to infer the compliance status with interval-averaged and with instantaneous occupational exposure limits from the results of longer-duration, integrated air sampling. AB - The duration of integrated air sampling for a substance may exceed the time frame of a substance's occupational exposure limit. Nonetheless, the compliance status of a limit may be inferred, under some circumstances, by the application of certain methods to the results of longer-duration samples. The purpose of this article is to define the inference methods and to illustrate their utility with actual and hypothetical examples. A review of articles and reports in U.S.-based Industrial Hygiene publications and databases revealed that the methods often were not but arguably should have been applied. Also revealed were inappropriate conclusions about the compliance status with exposure limits. Among the benefits of employing the inference methods is gaining information on exposures that might otherwise be overlooked. This article discusses the potential limitations of using the methods, and highlights some of the challenges of using integrated air sampling for assessing compliance with shorter-term exposure limits. PMID- 26366478 TI - A boron-doped helicene as a highly soluble, benchtop-stable green emitter. AB - The high-yield synthesis of a boron-doped [4]helicene was achieved through a Ni mediated Yamamoto C-C-coupling reaction; the moderate distortion of the molecular scaffold confers excellent solubility to the air- and water-stable green luminophore. PMID- 26366479 TI - General guidance on exploratory and confirmatory subgroup analysis in late-stage clinical trials. AB - This article focuses on a broad class of statistical and clinical considerations related to the assessment of treatment effects across patient subgroups in late stage clinical trials. This article begins with a comprehensive review of clinical trial literature and regulatory guidelines to help define scientifically sound approaches to evaluating subgroup effects in clinical trials. All commonly used types of subgroup analysis are considered in the article, including different variations of prospectively defined and post-hoc subgroup investigations. In the context of confirmatory subgroup analysis, key design and analysis options are presented, which includes conventional and innovative trial designs that support multi-population tailoring approaches. A detailed summary of exploratory subgroup analysis (with the purpose of either consistency assessment or subgroup identification) is also provided. The article promotes a more disciplined approach to post-hoc subgroup identification and formulates key principles that support reliable evaluation of subgroup effects in this setting. PMID- 26366480 TI - Propensity of Hydrated Excess Protons and Hydroxide Anions for the Air-Water Interface. AB - Significant effort has been undertaken to better understand the molecular details governing the propensity of ions for the air-water interface. Facilitated by computationally efficient reactive molecular dynamics simulations, new and statistically conclusive molecular-scale results on the affinity of the hydrated excess proton and hydroxide anion for the air-water interface are presented. These simulations capture the dynamic bond breaking and formation processes (charge defect delocalization) that are important for correctly describing the solvation and transport of these complex species. The excess proton is found to be attracted to the interface, which is correlated with a favorable enthalpic contribution and consistent with reducing the disruption in the hydrogen bond network caused by the ion complex. However, a recent refinement of the underlying reactive potential energy function for the hydrated excess proton shows the interfacial attraction to be weaker, albeit nonzero, a result that is consistent with the experimental surface tension measurements. The influence of a weak hydrogen bond donated from water to the protonated oxygen, recently found to play an important role in excess hydrated proton transport in bulk water, is seen to also be important for this study. In contrast, the hydroxide ion is found to be repelled from the air-water interface. This repulsion is characterized by a reduction of the energetically favorable ion-water interactions, which creates an enthalpic penalty as the ion approaches the interface. Finally, we find that the fluctuation in the coordination number around water sheds new light on the observed entropic trends for both ions. PMID- 26366482 TI - In This Issue: Cellular Stress and the Interface of Innate and Adaptive Immunity, and Other Topics. PMID- 26366481 TI - Can levothyroxine treatment reduce urinary albumin excretion rate in patients with early type 2 diabetic nephropathy and subclinical hypothyroidism? A randomized double-blind and placebo-controlled study. AB - OBJECTIVE: To investigate the effect of levothyroxine (LT4) therapy on urinary albumin excretion rate (UAER) in early type 2 diabetic nephropathy (DN) and subclinical hypothyroidism (SCH) patients with mildly increased thyroid stimulating hormone (TSH) levels and serum thyroid peroxidase antibody (TPO-Ab) positivity. METHODS: Application of randomized double-blind and placebo controlled methods. A total of 136 normotensive patients with early type 2 DN and SCH (TSH 4.0-7.0 mIU/L and TPO-Ab positive) were selected, and were randomly divided into two groups for LT4 or placebo treatments, respectively. Changes in UAER, serum creatinine, glomerular filtration rate (GFR), blood pressure, serum uric acid and lipids in patients before and after 48 weeks of treatment were examined and compared between groups. RESULTS: There were no statistically significant differences in the baseline characteristics of study participants between two treatment groups (p > 0.05 for all). After 48 weeks of treatment, compared to the placebo treatment, the LT4 treatment was more effective in reducing total cholesterol (p < 0.05). Further comparison of therapy-related differences between groups showed that the LT4 treatment was better in reducing UAER, low-density lipoprotein cholesterol and uric acid than the placebo group (p < 0.01 for all). CONCLUSION: The LT4 treatment may decrease UAER and exert kidney protection effects in early type 2 DN and SCH patients with mildly increased TSH levels and serum TPO-Ab positivity. However, due to the short duration of follow up and small number of cases, the results of this study need future trials with larger numbers of patients and longer follow-up periods to verify whether such a strategy can provide durable benefits. PMID- 26366483 TI - Distinguishing cubic and hexagonal phases within InGaN/GaN microstructures using electron energy loss spectroscopy. AB - 3D InGaN/GaN microstructures grown by metal organic vapor phase epitaxy (MOVPE) and molecular beam epitaxy (MBE) have been extensively studied using a range of electron microscopy techniques. The growth of material by MBE has led to the growth of cubic GaN material. The changes in these crystal phases has been investigated by Electron Energy Loss Spectroscopy, where the variations in the fine structure of the N K-edge shows a clear difference allowing the mapping of the phases to take place. GaN layers grown for light emitting devices sometimes have cubic inclusions in the normally hexagonal wurtzite structures, which can influence the device electronic properties. Differences in the fine structure of the N K-edge between cubic and hexagonal material in electron energy loss spectra are used to map cubic and hexagonal regions in a GaN/InGaN microcolumnar device. The method of mapping is explained, and the factors limiting spatial resolution are discussed. PMID- 26366484 TI - Global color estimation of special-effect coatings from measurements by commercially available portable multiangle spectrophotometers. AB - Colors of special-effect coatings have strong dependence on illumination/viewing geometry and an appealing appearance. An open question is to ask about the minimum number of measurement geometries required to completely characterize their observed color shift. A recently published principal components analysis (PCA)-based procedure to estimate the color of special-effect coatings at any geometry from measurements at a reduced set of geometries was tested in this work by using the measurement geometries of commercial portable multiangle spectrophotometers X-Rite MA98, Datacolor FX10, and BYK-mac as reduced sets. The performance of the proposed PCA procedure for the color-shift estimation for these commercial geometries has been examined for 15 special-effect coatings. Our results suggest that for rendering the color appearance of 3D objects covered with special-effect coatings, the color accuracy obtained with this procedure may be sufficient. This is the case especially if geometries of X-Rite MA98 or Datacolor FX10 are used. PMID- 26366485 TI - Fraunhofer diffraction of electromagnetic radiation by finite periodic structures with regular or irregular overall shapes. AB - Based on an essentially different theoretical foundation than common classical diffraction theories that remain in extensive use, this paper discusses from a fresh perspective the theoretical interpretation and prediction of the far-field diffraction of a plane monochromatic wave by a finite periodic array (PA) of identical obstacles. The theoretical treatment rests on the PA extension of the rigorous generalized multiparticle Mie solution (GMM). The truncated periodic structures may have an irregular overall shape with an arbitrary spatial orientation with respect to the incident beam. It is shown that the overall shape and intrinsic geometrical structure of a finite PA play a decisive role in giving rise to an associated far-field diffraction pattern. It is also shown that, when the physical dimensions of individual component units are much smaller than the incident wavelength, the extracted diffraction pattern of a densely packed PA of such small volumes in forward directions exhibits the distinct features predicted from classical diffraction theories for an aperture with the same shape as the overall finite PA. Several typical examples are presented, including two complementary arrays used in the specific discussion concerning Babinet's principle. There are brief preliminary discussions on some fundamental concepts in connection with the involved theoretical basis and on potential further development and application of the present GMM-PA approach. PMID- 26366486 TI - Saturation of multiplexed volume Bragg grating recording. AB - Recording of volume Bragg gratings (VBGs) in photo-thermo-refractive glass is limited to a maximum refractive index change about 0.002. We discuss various saturation curves and their influence on the amplitudes of recorded gratings. Special attention is given to multiplexed VBGs aimed at recording several gratings in the same volume. The best shape of the saturation curve for production of the strongest gratings is the threshold-type curve. Two-photon absorption as a mechanism of recording also allows increasing the strength of multiplexed VBGs. PMID- 26366487 TI - Color filter array patterns for small-pixel image sensors with substantial cross talk. AB - Digital image sensor outputs usually must be transformed to suit the human visual system. This color correction amplifies noise, thus reducing the signal-to-noise ratio (SNR) of the image. In subdiffraction-limit (SDL) pixels, where optical and carrier cross talk can be substantial, this problem can become significant when conventional color filter arrays (CFAs) such as the Bayer patterns (RGB and CMY) are used. We present the design and analysis of new color filter array patterns for improving the color error and SNR deterioration caused by cross talk in these SDL pixels. We demonstrate an improvement in the color reproduction accuracy and SNR in high cross-talk conditions. Finally, we investigate the trade-off between color accuracy and SNR for the different CFA patterns. PMID- 26366488 TI - Differentiability of a projection functional in ray-tracing processes: applied study to estimate the coefficients of a single lens with conic surfaces. AB - In optical design, many error functions can be used to generate an optical system with desired characteristics. These error functions are optimized by iterative algorithms. However, these error functions should be theoretically and mathematically differentiable to be optimized. In this paper, the differentiability of an error function is partially justified. The error function herein is called the projection functional. This proposed projection functional can be used to estimate the coefficients of an arbitrary lens with conic surfaces by means of the spot distributions on two planes produced by a fixed Hartmann plate. The differentiability of the projection functional is required to guarantee the existence of its Jacobian matrix, which is a suitable condition to minimize this functional by iterative methods. Numerical examples of the functional minimization are given. PMID- 26366489 TI - Absorption and scattering by bispheres, quadspheres, and circular rings of spheres and their equivalent coated spheres. AB - This study demonstrates that the absorption and scattering cross sections and asymmetry factor of randomly oriented and optically soft bispheres, quadspheres, and circular rings of spheres, with either monodisperse or polydisperse monomers, can be approximated by an equivalent coated sphere with identical volume and average projected area. This approximation could also apply to the angle dependent scattering matrix elements for monomer size parameter less than 0.1. However, it quickly deteriorated with increasing monomer number and/or size parameter. It was shown to be superior to previously proposed approximations considering a volume equivalent homogeneous sphere and a coated sphere with identical volume and surface area. These results provide a rapid and accurate way of predicting the radiation characteristics of bispheres, quadspheres, and rings of spheres representative of various unicellular and multicellular cyanobacteria considered for producing food supplements, biofuels, and fertilizers. They could also be used in inverse methods for retrieving the monomers' optical properties, morphology, and/or concentration. PMID- 26366490 TI - Application of complex geometrical optics to determination of thermal, transport, and optical parameters of thin films by the photothermal beam deflection technique. AB - In this work, complex geometrical optics is, for what we believe is the first time, applied instead of geometrical or wave optics to describe the probe beam interaction with the field of the thermal wave in photothermal beam deflection (photothermal deflection spectroscopy) experiments on thin films. On the basis of this approach the thermal (thermal diffusivity and conductivity), optical (energy band gap), and transport (carrier lifetime) parameters of the semiconductor thin films (pure TiO2, N- and C-doped TiO2, or TiO2/SiO2 composites deposited on a glass or aluminum support) were determined with better accuracy and simultaneously during one measurement. The results are in good agreement with results obtained by the use of other methods and reported in the literature. PMID- 26366491 TI - Polarization dependency of the metal-coated eccentric fiber. AB - The transmission losses and lengths of two polarized fundamental modes for a metal-coated eccentric core optical fiber (ECOF) are considered based on the finite-element method. Three typical thin metal films (Au, Ag, and Cu) are used and deposited on the walls of the cladding of ECOF. The variations of the transmission losses and lengths are investigated with different eccentricity, core radii, and metal film species. The numerical results indicate that the optical spectrum of a metal-coated ECOF can be tuned easily by changing the structure parameters of the fiber. The fundamental mode of metal-coated ECOF shows good polarization dependency. It is forecasted that the attenuation difference between the two polarization modes may be used to design an in-fiber polarizer. PMID- 26366492 TI - DMD-based implementation of patterned optical filter arrays for compressive spectral imaging. AB - Compressive spectral imaging (CSI) captures multispectral imagery using fewer measurements than those required by traditional Shannon-Nyquist theory-based sensing procedures. CSI systems acquire coded and dispersed random projections of the scene rather than direct measurements of the voxels. To date, the coding procedure in CSI has been realized through the use of block-unblock coded apertures (CAs), commonly implemented as chrome-on-quartz photomasks. These apertures block or permit us to pass the entire spectrum from the scene at given spatial locations, thus modulating the spatial characteristics of the scene. This paper extends the framework of CSI by replacing the traditional block-unblock photomasks by patterned optical filter arrays, referred to as colored coded apertures (CCAs). These, in turn, allow the source to be modulated not only spatially but spectrally as well, entailing more powerful coding strategies. The proposed CCAs are synthesized through linear combinations of low-pass, high-pass, and bandpass filters, paired with binary pattern ensembles realized by a digital micromirror device. The optical forward model of the proposed CSI architecture is presented along with a proof-of-concept implementation, which achieves noticeable improvements in the quality of the reconstruction. PMID- 26366493 TI - Rotation dynamics of particles trapped in a rotating beam. AB - The rotation dynamics of particles trapped in a rotating beam is theoretically investigated. We find that there is a critical angular speed for the rotating beam. If the angular speed of the rotating beam is smaller than the critical value, the angular velocity of the trapped particle is nearly the same as that of the rotating beam, which is in accord with existing experimental observation. Otherwise, the angular velocity of the trapped particles will become periodic or quasi-periodic with time, depending on the beam polarization, which, to the best of our knowledge, has not been previously reported. Moreover, we also propose some methods to determine the ratio between the beam power and the maximal angular speed of the trapped particle, which can be used to estimate the minimum power required to rotate the particle at a given angular speed. PMID- 26366494 TI - Performance of binoculars: Berek's model of target detection. AB - A model of target detection thresholds, first presented by Max Berek of Leitz, is fitted into a simple set of closed equations. These are combined with a recently published universal formula for the human eye's pupil size to yield a versatile formalism that is capable of predicting binocular performance gains. The model encompasses target size, contrast, environmental luminance, binocular's objective diameter, magnification, angle of view, transmission, stray light, and the observer's age. We analyze performance parameters of various common binocular models and compare the results with popular approximations to binocular performance, like the well-known twilight index. The formalisms presented here are of interest in military target detection as well as in civil applications such as hunting, surveillance, object security, law enforcement, and astronomy. PMID- 26366495 TI - Design of dense transmission diffraction gratings for high efficiency. AB - We propose a design method for dense surface-relief diffraction gratings with high efficiency in transmission mode. Closed-form analytical relations between diffraction efficiency, polarization, and grating parameters are derived and verified in the resonance domain of diffraction under general three-dimensional angles of incidence traditionally termed conical mounting. A powerful tool for rigorous design of computer-generated holograms and diffractive optical elements with spectroscopic scale periods is now enabled. PMID- 26366496 TI - Parabasal thin-element approximation approach for the analysis of microstructured interfaces and freeform surfaces. AB - The thin-element approximation (TEA) approach is an efficient algorithm to analyze microstructured interfaces, e.g., diffractive optical elements or scattering surfaces. However, the classical approach is valid only under the condition of paraxial illumination. We hereby develop an extended algorithm to include parabasal illumination, which is characterized by low divergence with arbitrary propagation direction. The extended approach is named as the parabasal TEA approach. In this paper, we present the algorithm of the parabasal TEA approach and compare the results with that of a rigorous calculation in order to demonstrate its validity. We also discuss the role of the parabasal TEA approach in a more general concept for modeling light propagating through freeform surfaces. PMID- 26366497 TI - Radiation force exerted on a sphere by focused Laguerre-Gaussian beams. AB - The generalized Lorenz-Mie theory is employed to calculate the force exerted on a sphere by focused Laguerre-Gaussian beams. The key parameters of the theory, namely, the multipole coefficients of the beams, are exactly derived from the beams' angular spectra in terms of some auxiliary coefficients. Several recurrence formulas, which can improve the calculation of the auxiliary coefficients and accordingly the force, are also derived. According to the calculated force, the trapping performances of the beams are investigated in the Mie regime. It is found that low(high)-azimuthal-order beams usually have advantages in the radial trapping of the high(low)-refractive-index sphere and the axial trapping of the low(high)-refractive-index sphere. The influences of the parameters of the beams, lens, and sphere on the trapping performance are also investigated. PMID- 26366498 TI - Curvilinear coordinate method as an initial value problem: application to gratings. AB - We propose a C-method approach for the efficient calculation of the scattering matrix of a grating. We consider two horizontal planes above and below the grating and define a coordinate system such that the grating surface and both horizontal planes correspond to surface coordinates. Inside the area A delimited by the horizontal planes, the covariant formalism of Maxwell's equations leads to an initial value problem that is solved for independent initial conditions satisfying the boundary conditions. Outside the area A, the fields are represented by Rayleigh expansions. The scattering matrix is obtained by using continuity relations between different components of fields on the horizontal planes. PMID- 26366499 TI - Generation of cylindrically symmetric modes and orbital-angular-momentum modes with tilted optical gratings inscribed in high-numerical-aperture fibers. AB - Optical fiber with high numerical aperture (NA) can efficiently relieve the degeneracy of higher-order linearly polarized modes. The degeneracy relief is investigated in two types of high-NA fibers, i.e., low-index-cladding fiber and high-index-core fiber. A naked-core fiber, as with low-index cladding, can be used theoretically to generate the orbital-angular-momentum mode (OAMM) HE21 and the cylindrically symmetric modes (CSMs) TM01 and TE01. A high-index-core fiber incorporated with high-contrast-index structure can be used similarly to obtain OAMM HE31. The generation of both CSMs and OAMMs required tilted optical gratings to couple the fundamental core mode HE11 into these modes. The tilt angle and modulation period of the grating fringes can be calculated simply and visually with the method proposed in this article. PMID- 26366500 TI - Method for pan-tilt camera calibration using single control point. AB - The pan-tilt (PT) camera is widely used in video surveillance systems due to its rotatable property and low cost. The rough output of a PT camera may not satisfy the demand of practical applications; hence an accurate calibration method of a PT camera is desired. However, high-precision camera calibration methods usually require sufficient control points not guaranteed in some practical cases of a PT camera. In this paper, we present a novel method to online calibrate the rotation angles of a PT camera by using only one control point. This is achieved by assuming that the intrinsic parameters and position of the camera are known in advance. More specifically, we first build a nonlinear PT camera model with respect to two parameters Pan and Tilt. We then convert the nonlinear model into a linear model according to sine and cosine of Tilt, where each element in the augmented coefficient matrix is a function of the single variable Pan. A closed form solution of Pan and Tilt can then be derived by solving a quadratic equation of tangent of Pan. Our method is noniterative and does not need features matching; thus its time efficiency is better. We evaluate our calibration method on various synthetic and real data. The quantitative results demonstrate that the proposed method outperforms other state-of-the-art methods if the intrinsic parameters and position of the camera are known in advance. PMID- 26366501 TI - Pemetrexed and interstitial lung disease. PMID- 26366502 TI - Risk factors for shoulder pain and injury in swimmers: A critical systematic review. AB - Swimming is one of the most popular recreational and competitive sporting activities. In the 2013/2014 swimming season, 9630 men and 12,333 women were registered with the National Collegiate Athletics Association in the USA. The repetitive nature of the swimming stroke and demanding training programs of its athletes raises a number of concerns regarding incidence and severity of injuries that a swimmer might experience during a competitive season. A number of risk factors have previously been identified but the level of evidence from individual studies, as well as the level of certainty that these factors predispose a swimmer to pain and injury, to our knowledge has yet to be critically evaluated in a systematic review. Therefore, the primary objective of this review is to conduct a systematic review to critically assess the published evidence for risk factors that may predispose a swimmer to shoulder pain and injury. Three electronic databases, ScienceDirect, PubMed and SpringerLink, were searched using keywords "(Injury OR pain) AND (Swim*)" and "(Shoulder) AND (Swim*)". Based on the inclusion and exclusion criteria, 2731 unique titles were identified and were analyzed to a final 29 articles. Only articles with a level of evidence of I, II and III were included according to robust study design and data analysis. The level of certainty for each risk factor was determined. No studies were determined to have a high level of certainty, clinical joint laxity and instability, internal/external rotation, previous history of pain and injury and competitive level were determined to have a moderate level of certainty. All other risk factors were evaluated as having a low level of certainty. Although several risk factors were identified from the reviewed studies, prospective cohort studies, larger sample sizes, consistent and robust measures of risk should be employed in future research. PMID- 26366503 TI - Kinetics of Cr(III) and Cr(VI) removal from water by two floating macrophytes. AB - The aim of this work was to compare Cr(III) and Cr(VI) removal kinetics from water by Pistia stratiotes and Salvinia herzogii. The accumulation in plant tissues and the effects of both Cr forms on plant growth were also evaluated. Plants were exposed to 2 and 6 mg L(-1) of Cr(III) or Cr(VI) during 30 days. At the end of the experiment, Cr(VI) removal percentages were significantly lower than those obtained for Cr(III) for both macrophytes. Cr(III) removal kinetics involved a fast and a slow component. The fast component was primarily responsible for Cr(III) removal while Cr(VI) removal kinetics involved only a slow process. Cr accumulated principally in the roots. In the Cr(VI) treatments a higher translocation from roots to aerial parts than in Cr(III) treatments was observed. Both macrophytes demonstrated a high ability to remove Cr(III) but not Cr(VI). Cr(III) inhibited the growth at the highest studied concentration of both macrophytes while Cr(VI) caused senescence. These results have important implications in the use of constructed wetlands for secondary industrial wastewater treatment. Common primary treatments of effluents containing Cr(VI) consists in its reduction to Cr(III). Cr(III) concentrations in these effluents are normally below the highest studied concentrations in this work. PMID- 26366504 TI - Secular trends in the interest of physical health in patients with mental illness. PMID- 26366505 TI - Pharmacokinetics and tissue distribution study of 16-dehydropregnenolone liposome in female mice after intravenous administration. AB - OBJECTIVE: 16-Dehydropregnenolone (16-DHP) is a potential antitumor compound with poor solubility. A liposome entrapped 16-DHP (16-DHP-LM) formulation was developed to surmount its solubility obstacle. The aim of this study is to investigate the pharmacokinetics of 16-DHP-LM and 16-DHP solution in female mice and tissue distribution of 16-DHP-LM in female tumor-bearing nude mice. METHODS: Rotary-evaporated film method was used to prepare 16-DHP-LM. The comparison of pharmacokinetics between 16-DHP-LM and 16-DHP solution in female mice was investigated after intravenous administration at a single dose of 15 mg/kg. The dose proportionality of 16-DHP-LM was also evaluated after intravenous administration of 16-DHP-LM at the doses of 7.5, 15.0 and 30.0 mg/kg. The tissue distribution of 16-DHP-LM in female tumor-bearing nude mice was evaluated after intravenous administration of 16-DHP-LM at a single dose of 30.0 mg/kg. RESULTS: The pharmacokinetic study indicated that the 16-DHP-LM group had higher area under the plasma concentration-time curve (AUC), lower apparent volume of distribution (Vz) and smaller systemic clearance (CL) than the 16-DHP solution group. For dose proportionality, good linearity of the pharmacokinetics of 16-DHP after intravenous administration of 16-DHP-LM was observed in the regression analysis of the AUC-dose plot (r = 0.99) and the Cmax-dose plot (r = 0.98). The tissue distribution study showed that the main tissue depots for 16-DHP in tumor bearing nude mice were plasma, liver, spleen and tumor, which was benefit to anti tumor effect. All these results provided a significant basis for the design of clinical trial of 16-DHP-LM. PMID- 26366506 TI - Morbidity and Mortality Associated With Anogenital Human Papillomavirus "Low Risk" Genotypes. PMID- 26366507 TI - Rapidly Invasive Buschke-Lowenstein Tumor Associated With Human Papillomavirus Types 6 and 52. AB - Buschke-Lowenstein tumor, or giant condyloma acuminatum, represents a rare, sexually transmitted disorder, with a slow evolution and the tendency to infiltrate in the adjacent tissues associated with human papillomavirus (HPV). This article reports the first case of male Buschke-Lowenstein tumor associated with HPV6 and HPV52. PMID- 26366508 TI - Use of Expedited Partner Therapy for Sexually Transmitted Diseases in College and University Health Centers in the United States, 2011-2012. AB - We examined expedited partner therapy for chlamydia and gonorrhea in college and university health centers by institutional and policy characteristics. Expedited partner therapy awareness and use was low (44.1% used), did not differ by institutional characteristics, and differed by policy environment. Our findings suggest missed opportunities for sexually transmitted disease prevention in college and university health centers. PMID- 26366509 TI - Previously Identified "k" Sequence Variants of the tp0548 Gene Will Be Renamed as Type "l". PMID- 26366510 TI - Estimating the Total Annual Direct Cost of Providing Sexually Transmitted Infection and HIV Testing and Counseling for Men Who Have Sex With Men in the United States. AB - BACKGROUND: The Centers for Disease Control and Prevention recommends annual sexually transmitted infection (STI) and HIV testing and counseling for men who have sex with men (MSM) in the United States. We estimated the annual total direct medical cost of providing recommended STI and HIV testing and counseling services for MSM in the United States. METHODS: We included costs for 9 STI (including anatomic site-specific) tests recommended by the Centers for Disease Control and Prevention (HIV, syphilis, gonorrhea, chlamydia, hepatitis B viral infection, and herpes simplex virus type 2), office visits, and counseling. We included nongenital tests for MSM with exposure at nongenital sites. All cost data were obtained from the 2012 MarketScan outpatient claims database. Men were defined as MSM if they had a male sex partner within the last 12 months, which was estimated at 2.9% (2.6%-3.2%) of the male population in a 2012 study. All costs were updated to 2014 US dollars. RESULTS: The estimated average costs were as follows: HIV ($18 [$9-$27]), hepatitis B viral infection ($23 [$12-$35]), syphilis ($8 [$4-$11]), gonorrhea and chlamydia ($45 [$22-$67]) per anatomic site), herpes simplex virus type 2 ($27 [$14-$41]), office visit ($100 [$50 $149]), and counseling ($29 [$15-$44]). We estimated that the total annual direct cost of a universal STI and HIV testing and counseling program was $1.1 billion ($473 million-$1.7 billion) for all MSM and $756 (range, $338-$1.2 billion) when excluding office visit cost. CONCLUSIONS: These estimates provide the potential costs associated with universal STI and HIV testing and counseling for MSM in the United States. This information may be useful in future cost and/or cost effectiveness analyses that can be used to evaluate STI and HIV prevention efforts. PMID- 26366511 TI - Systems Approaches to Improving Rates of Extragenital Chlamydia and Gonorrhea Screening Among Men Who Have Sex With Men Engaged in Human Immunodeficiency Virus Care. PMID- 26366512 TI - Does pregnancy-induced hypertension affect the electrophysiology of the heart? AB - Pregnancy-induced hypertension (PIHT) increases both maternal and neonatal mortality and morbidity in pregnant women. We sought to investigate the electrocardiographic findings in pregnant women with PIHT. Seventeen pregnant women (29.4 +/- 5 years) with PIHT and 24 pregnant women (27.3 +/- 6.1 years) with normal blood pressure (control group) were included in the study. A 12-lead surface electrocardiogram was used to evaluate the electrocardiographic parameters. Pregnant women with PIHT had higher blood pressure (p = 0.001). The Tp-e interval was longer in PIHT pregnant women at 83.5 +/- 7.8 ms versus 75.8 +/ 8.4 ms in the control group (p = 0.007). The Tp-e/QTc ratio was higher in pregnant women with PIHT than that in healthy controls (0.19 +/- 0.02 vs. 0.18 +/ 0.02, respectively). This study demonstrated that Pd, QTd and the P wave durations were similar in the PIHT pregnant women and control group, but the Tp-e and Tp-e/QTc ratio were higher in pregnant women with PIHT than in normotensive pregnant women. PMID- 26366514 TI - Mechanical Properties of Plasma Immersion Ion Implanted PEEK for Bioactivation of Medical Devices. AB - Plasma immersion ion implantation (PIII) is used to modify the surface properties of polyether ether ketone for biomedical applications. Modifications to the mechanical and chemical properties are characterized as a function of ion fluence (treatment time) to determine the suitability of the treated surfaces for biological applications. Young's modulus and elastic recovery were found to increase with respect to treatment time at the surface from 4.4 to 5.2 MPa and from 0.49 to 0.68, respectively. The mechanical properties varied continuously with depth, forming a graded layer where the mechanical properties returned to untreated values deep within the layer. The treated surface layer exhibited cracking under cyclical loads, associated with an increased modulus due to dehydrogenation and cross-linking; however, it did not show any sign of delamination, indicating that the modified layer is well integrated with the substrate, a critical factor for bioactive surface coatings. The oxygen concentration remained unchanged at the surface; however, in contrast to ion implanted polymers containing only carbon and hydrogen, the oxygen concentration within the treated layer was found to decrease. This effect is attributed to UV exposure and suggests that PIII treatments can modify the surface to far greater depths than previously reported. Protein immobilization on PIII treated surfaces was found to be independent of treatment time, indicating that the surface mechanical properties can be tuned for specific applications without affecting the protein coverage. Our findings on the mechanical properties demonstrate such treatments render PEEK well suited for use in orthopedic implantable devices. PMID- 26366515 TI - Noninvasive measurement of intracranial pressure via the pulsatility index on transcranial Doppler sonography: Is improvement possible? AB - PURPOSE: We hypothesized that using hemodynamic variables could improve the prediction of intracranial pressure (ICP) from the middle cerebral artery pulsatility index (PI) measured with transcranial Doppler sonography. METHODS: In this prospective study, 39 patients with traumatic brain injury were routinely examined with transcranial Doppler sonography, and the middle cerebral artery PI was calculated. A multivariate model including hematocrit, mean arterial blood pressure, heart rate, and arterial CO2 pressure (PaCO2 ) was evaluated. RESULTS: Thirty-nine comatose patients (16 women and 23 men; age range 18-73 years; median 44 years) were included, and 234 data pairs (consisting of ICP and corresponding PI values) were analyzed. ICP ranged from -3 mmHg to +52 mmHg, and PI from 0.6 to 2.85. We found a significant but weak correlation between PI and the square root of ICP (R(2) between 0.29 and 0.34, p < 0.0001). A slightly stronger correlation was detected when hemodynamic variables were incorporated (R(2) between 0.37 and 0.43). Of these variables, mean arterial blood pressure had the most significant influence. CONCLUSIONS: In this study, PI was not a sufficiently strong predictor of ICP to be used in clinical practice. Its reliability did not improve even when hemodynamic variables were considered. Therefore, we recommend abandoning the use of PI for the noninvasive measurement of ICP in clinical practice. PMID- 26366516 TI - Doctors and Their Workshops. PMID- 26366513 TI - REM sleep behavior disorder, as assessed by questionnaire, in G2019S LRRK2 mutation PD and carriers. AB - BACKGROUND: Rapid eye movement sleep behavior disorder occurs with idiopathic Parkinson's disease (PD) and often precedes PD. Its frequency in LRRK2-PD and utility as a preclinical marker has not been established. METHODS: One hundred forty-four idiopathic PD, 142 LRRK2 G2019S mutation PD, 117 non-manifesting carriers, 93 related noncarriers, and 40 healthy controls completed the Rapid eye movement sleep Behavior Disorder Screening Questionnaire. RESULTS: Cut scores were met by 30.6% idiopathic PD, 19.7% LRRK2-PD, 6% nonmanifesting carriers, 20.4% related noncarriers, and 15% controls. The likelihood of abnormal scores was decreased in LRRK2-PD versus idiopathic PD (odds ratio = 0.55, P = 0.03), nonmanifesting carriers versus related noncarriers (OR = 0.25, P < 0.01), and PD of less than 3 years' duration, 1 of 19 LRRK2-PD versus 14 of 41 idiopathic PD (P < 0.05). CONCLUSIONS: A lower frequency of abnormal questionnaire scores is seen in LRRK2-PD, especially in early LRRK2-PD, and in nonmanifesting carriers. Therefore, the Rapid eye movement sleep Behavior Disorder Questionnaire is unlikely to serve as a preclinical marker for phenoconversion to PD. PMID- 26366517 TI - Will the RN Workforce Weather the Retirement of the Baby Boomers? AB - IMPORTANCE: After forecasts made more than a decade ago suggested dire nursing shortages, enrollment in nursing schools doubled. The implications of this unprecedented change for the nursing workforce have not yet been fully explored. OBJECTIVE: To forecast the size and age distribution of the nursing workforce to the year 2030 and to compare to demand recently projected by the Health Resources and Services Agency. DESIGN: A retrospective cohort analysis of employment trends by birth year and age were used to project age and employment of registered nurses (RNs) through 2030. SETTING: Data on employed RNs from the United States Bureau of the Census Current Population Survey (1979-2000, N=72,222) and American Community Survey (2001-2013, N=342,712). PARTICIPANTS: RNs between the ages of 23 and 69 years. MAIN OUTCOME MEASURE: Annual full-time equivalent (FTE) employment of RNs in total and by single year of age. RESULTS: Annual retirements from the nursing workforce will accelerate from 20,000 a decade ago to near 80,000 in the next decade as baby boomer RNs continue to age. We project that this outflow will be more than offset by continued strong entry of new RNs into the workforce. Overall, we project that the registered nursing workforce will increase from roughly 2.7 million FTE RNs in 2013 to 3.3 million in 2030. We also find that the workforce will reach its peak average age in 2015 at 44.4. This increase in workforce size, which was not expected in forecasts made a decade ago, is contingent on new entry into nursing continuing at its current rate. Even then, supply would still fall short of demand as recently projected by the Health Resources and Services Agency in the year 2025 by 128,000 RNs (4%). CONCLUSIONS: The unexpected surge of entry of new RNs into the workforce will lead to continued net growth of the nursing workforce, both in absolute FTE and FTE per capita. While this growth may not be sufficient to meet demand, such projections are uncertain in the face of a rapidly evolving health care delivery system. PMID- 26366518 TI - Patient-centered Medical Homes and Access to Services for New Primary Care Patients. AB - BACKGROUND: Recent efforts to revitalize primary care have centered on the patient-centered medical home (PCMH). Although enhanced access is an integral component of the PCMH model, the effect of PCMHs on access to primary care services is understudied. OBJECTIVE: To determine whether PCMH practices are associated with better access to new appointments for nonelderly adults by direct measurement. RESEARCH DESIGN: We estimated the relationship between practice PCMH status and access to care in multivariate regression models, adjusting for a robust set of patient, practice, and geographic characteristics; using data on 11,347 simulated patient calls to 7266 primary care practices across 10 US states merged with data on PCMH practices. PARTICIPANTS: Trained field staff posing as patients (age younger than 65 y) seeking a new primary care appointment with varying insurance status (private, Medicaid, or self-pay). MEASURES: Our primary predictor was practice PCMH status and our primary outcome was the ability of simulated patients to schedule a new appointment. Secondary outcomes included the number of days to that appointment; availability of after-hour appointments; and an appointment with an ongoing primary care provider. RESULTS: Of the 7266 practices contacted for an appointment, 397 (5.5%) were National Committee for Quality Assurance-recognized PCMHs. In adjusted analyses, callers to PCMH practices compared with non-PCMH practices were more likely to schedule a new appointment (adjusted odds ratio=1.26 (95% CI, 1.01-1.58); P=0.04] and be offered after-hour appointments [adjusted odds ratio=1.36 (95% CI, 1.04-1.75); P=0.02]. DISCUSSION: PCMH practices maybe associated with better access to new primary care appointments for nonelderly adults, those most likely to gain insurance under the Affordable Care Act. PMID- 26366520 TI - A Comparison of Quality of Community Health Services Between Public and Private Community Health Centers in Urban China. AB - BACKGROUND: This study was the first of its kind to evaluate and compare the quality of private and public community health centers (CHCs) in urban China. METHODS: A total of 2501 CHCs in 35 cities were chosen in 2011 using a multistage sampling method, and data on human resources, medical equipment and drug inventory were collected. A subset of 422 CHCs was randomly selected and 100 prescriptions from each CHCs were reviewed to evaluate prescribing practice. In total, 12,386 patients who visited the selected 422 CHCs were interviewed to assess patient satisfaction and payments. RESULTS: Controlling for population covered per CHC and geographic regions, private CHCs were higher than public CHCs in average building area (2310.96 vs. 2000.92 square meters), average number of medical equipment (6.42 vs. 6.14), average number of physicians and nurses per 10,000 population (4.86 vs. 3.81 and 3.38 vs. 2.62), and average number of medicines in stock (435.08 vs. 375.83), but lower in average percentage of medicines on the national essential medicines list (67.29% vs. 77.55%). Prescriptions from private CHCs had significantly higher number of drugs per prescription (2.38 vs. 2.24), higher percentage of prescriptions with injections (36.44% vs. 30.50%), and higher percentage of prescriptions with antibiotics (37.17% vs. 30.14%). Patient satisfaction was similar between the 2 groups, and patient payments per visit were lower in private CHCs after controlling for patients' sociodemographic characteristics. CONCLUSIONS: Private CHCs are better equipped and better staffed than public CHCs but are less compliant with national policy on essential medicines and have poorer prescribing quality in China, warranting more rigorous government supervision. PMID- 26366519 TI - Racial/Ethnic Disparities in Time to a Breast Cancer Diagnosis: The Mediating Effects of Health Care Facility Factors. AB - BACKGROUND: Racial/ethnic disparities exist along the breast cancer continuum, including time to a diagnosis. Previous research has largely focused on patient level factors, and less is known about the role that health care facilities may play in delayed breast cancer care. OBJECTIVES: We examined racial/ethnic disparities in delayed diagnosis for breast cancer in the Breast Cancer Care in Chicago Study and estimated the potential mediating effects of facility factors. RESEARCH DESIGN AND SUBJECTS: Breast cancer patients (N=606) contributed interview and medical record data as part of a population-based study. MEASURES: Race/ethnicity was self-reported at interview. Diagnostic delay was defined as an excess of 60 days between medical presentation and a definitive diagnosis. Facility factors included the facility of medical presentation with respect to: (1) accreditation through the National Consortium of Breast Centers; (2) certification as a Breast Imaging Center of Excellence through the American College of Radiology; and (3) status as a disproportionate share hospital through the state of Illinois as well as the number of facilities used between presentation and diagnosis. RESULTS: Relative to non-Hispanic whites, minorities were more likely to experience a diagnostic delay, present at a nonaccredited facility and at a disproportionate share hospital, and involve multiple facilities in their diagnosis. Together, facility factors accounted for 43% of the disparity in diagnostic delay (P<0.0001). CONCLUSIONS: Initial presentation of breast cancer at higher resourced facilities can reduce diagnostic delays. Disparities in delay are partly due to a disproportionate presentation at lower resourced facilities by minorities. PMID- 26366521 TI - Confirmatory Factor Analysis of the Patient Reported Outcomes Measurement Information System (PROMIS) Adult Domain Framework Using Item Response Theory Scores. AB - BACKGROUND: To guide measure development, National Institutes of Health-supported Patient reported Outcomes Measurement Information System (PROMIS) investigators developed a hierarchical domain framework. The framework specifies health domains at multiple levels. The initial PROMIS domain framework specified that physical function and symptoms such as Pain and Fatigue indicate Physical Health (PH); Depression, Anxiety, and Anger indicate Mental Health (MH); and Social Role Performance and Social Satisfaction indicate Social Health (SH). We used confirmatory factor analyses to evaluate the fit of the hypothesized framework to data collected from a large sample. METHODS: We used data (n=14,098) from PROMIS's wave 1 field test and estimated domain scores using the PROMIS item response theory parameters. We then used confirmatory factor analyses to test whether the domains corresponded to the PROMIS domain framework as expected. RESULTS: A model corresponding to the domain framework did not provide ideal fit [root mean square error of approximation (RMSEA)=0.13; comparative fit index (CFI)=0.92; Tucker Lewis Index (TLI)=0.88; standardized root mean square residual (SRMR)=0.09]. On the basis of modification indices and exploratory factor analyses, we allowed Fatigue to load on both PH and MH. This model fit the data acceptably (RMSEA=0.08; CFI=0.97; TLI=0.96; SRMR=0.03). DISCUSSION: Our findings generally support the PROMIS domain framework. Allowing Fatigue to load on both PH and MH improved fit considerably. PMID- 26366522 TI - Supramolecular Translation of Enzymatically Triggered Disassembly of Micelles into Tunable Fluorescent Responses. AB - The need for advanced fluorescent imaging and delivery platforms has motivated the development of smart probes that change their fluorescence in response to external stimuli. Here a new molecular design of fluorescently labeled PEG dendron hybrids that self-assemble into enzyme-responsive micelles with tunable fluorescent responses is reported. In the assembled state, the fluorescence of the dyes is quenched or shifted due to intermolecular interactions. Upon enzymatic cleavage of the hydrophobic end-groups, the labeled polymeric hybrids become hydrophilic, and the micelles disassemble. This supramolecular change is translated into a spectral response as the dye-dye interactions are eliminated and the intrinsic fluorescence is regained. We demonstrate the utilization of this molecular design to generate both Turn-On and spectral shift responses by adjusting the type of the labeling dye. This approach enables transformation of non-responsive labeling dyes into smart fluorescent probes. PMID- 26366523 TI - Altered Immunogenicity of Donor Lungs via Removal of Passenger Leukocytes Using Ex Vivo Lung Perfusion. AB - Passenger leukocyte transfer from the donor lung to the recipient is intrinsically involved in acute rejection. Direct presentation of alloantigen expressed on donor leukocytes is recognized by recipient T cells, promoting acute cellular rejection. We utilized ex vivo lung perfusion (EVLP) to study passenger leukocyte migration from donor lungs into the recipient and to evaluate the effects of donor leukocyte depletion prior to transplantation. For this purpose, female pigs received male left lungs either following 3 h of EVLP or retrieved using standard protocols. Recipients were monitored for 24 h and sequential samples were collected. EVLP-reduced donor leukocyte transfer into the recipient and migration to recipient lymph nodes was markedly reduced. Recipient T cell infiltration of the donor lung was significantly diminished via EVLP. Donor leukocyte removal during EVLP reduces direct allorecognition and T cell priming, diminishing recipient T cell infiltration, the hallmark of acute rejection. PMID- 26366524 TI - Impact of different magnification levels on visual caries detection with ICDAS. AB - OBJECTIVES: The aim of this in vitro study was to examine the effect of different levels of magnification on the accuracy and reliability of visual caries detection using ICDAS criteria. METHODS: Occlusal surfaces of 100 extracted molars were assessed by 14 examiners (3rd and the 4th year dental students and dentists) using no magnification aids, a 2.5* Galilean loupe, a 4.5* Keplerian loupe, or a surgical microscope with 10* magnification. The assessments were repeated on a different day. Sensitivity, specificity, AUC and reliabilities were calculated according to the gold standard of histology. RESULTS: We found that with increasing magnification, the number of surfaces rated as "sound" (ICDAS code 0) decreased, while the number of surfaces with a localized enamel breakdown (ICDAS code 3) increased. While the sensitivities increased, the values of the specificities decreased to an unacceptably low level irrespective of the clinical experience of the examiners. CONCLUSIONS: ICDAS seems to be optimized for natural vision up to 2.0* magnification and not for high magnifications. The use of powerful magnification in visual caries detection involves the risk of unnecessary and premature invasive treatment. CLINICAL SIGNIFICANCE: This paper discusses when it does and does not make sense to use magnification devices for visual caries detection using ICDAS criteria. Strong magnifications should be refrained from for this purpose. PMID- 26366526 TI - Machine Learnable Fold Space Representation based on Residue Cluster Classes. AB - MOTIVATION: Protein fold space is a conceptual framework where all possible protein folds exist and ideas about protein structure, function and evolution may be analyzed. Classification of protein folds in this space is commonly achieved by using similarity indexes and/or machine learning approaches, each with different limitations. RESULTS: We propose a method for constructing a compact vector space model of protein fold space by representing each protein structure by its residues local contacts. We developed an efficient method to statistically test for the separability of points in a space and showed that our protein fold space representation is learnable by any machine-learning algorithm. AVAILABILITY: An API is freely available at https://code.google.com/p/pyrcc/. PMID- 26366525 TI - Exercise dependent increase in axon regeneration into peripheral nerve grafts by propriospinal but not sensory neurons after spinal cord injury is associated with modulation of regeneration-associated genes. AB - Insufficient regeneration of central nervous system (CNS) axons contributes to persisting neurological dysfunction after spinal cord injury (SCI). Peripheral nerve grafts (PNGs) support regeneration by thousands of injured intraspinal axons and help them bypass some of the extracellular barriers that form after SCI. However this number represents but a small portion of the total number of axons that are injured. Here we tested if rhythmic sensory stimulation during cycling exercise would boost the intrinsic regenerative state of neurons to enhance axon regeneration into PNGs after a lower thoracic (T12) spinal transection of adult rats. Using True Blue retrograde tracing, we show that 4 weeks of cycling improves regeneration into a PNG from lumbar interneurons but not by primary sensory neurons. The majority of neurons that regenerate their axon are within 5 mm of the lesion and their number increased 70% with exercise. Importantly propriospinal neurons in more distant regions (5-20 mm from the lesion) that routinely exhibit very limited regeneration responded to exercise by increasing the number of regenerating neurons by 900%. There was no exercise associated increase in regeneration from sensory neurons. Analyses using fluorescent in situ hybridization showed that this increase in regenerative response is associated with changes in levels of mRNAs encoding the regeneration associated genes (RAGs) GAP43, beta-actin and Neuritin. While propriospinal neurons showed increased mRNA levels in response to SCI alone and then to grafting and exercise, sensory neurons did not respond to SCI, but there was a response to the presence of a PNG. Thus, exercise is a non-invasive approach to modulate gene expression in injured neurons leading to an increase in regeneration. This sets the stage for future studies to test whether exercise will promote axon outgrowth beyond the PNG and reconnection with spinal cord neurons, thereby demonstrating a potential clinical application of this combined therapeutic intervention. PMID- 26366527 TI - Abundance of intrinsic structural disorder in the histone H1 subtypes. AB - The intrinsically disordered proteins consist of partially structured regions linked to the unstructured stretches, which consequently form the transient and dynamic conformational ensembles. They undergo disorder to order transition upon binding their partners. Intrinsic disorder is attributed to histones H1, perceived as assemblers of chromatin structure and the regulators of DNA and proteins activity. In this work, the comparison of intrinsic disorder abundance in the histone H1 subtypes was performed both by the analysis of their amino acid composition and by the prediction of disordered stretches, as well as by identifying molecular recognition features (MoRFs) and ANCHOR protein binding regions (APBR) that are responsible for recognition and binding. Both human and model organisms-animals, plants, fungi and protists-have H1 histone subtypes with the properties typical of disordered state. They possess a significantly higher content of hydrophilic and charged amino acid residues, arranged in the long regions, covering over half of the whole amino acid residues in chain. Almost complete disorder corresponds to histone H1 terminal domains, including MoRFs and ANCHOR. Those motifs were also identified in a more ordered histone H1 globular domain. Compared to the control (globular and fibrous) proteins, H1 histones demonstrate the increased folding rate and a higher proportion of low-complexity segments. The results of this work indicate that intrinsic disorder is an inherent structural property of histone H1 subtypes and it is essential for establishing a protein conformation which defines functional outcomes affecting on DNA- and/or partner protein-dependent cell processes. PMID- 26366529 TI - Solvation Mechanism of Task-Specific Ionic Liquids in Water: A Combined Investigation Using Classical Molecular Dynamics and Density Functional Theory. AB - The solvation behavior of task-specific ionic liquids (TSILs) containing a common, L-histidine derived imidazolium cation [C20H28N3O3](+) and different anions, bromide-[Br](-) and bis(trifluoromethylsulfonyl)amide-[NTF2](-), in water is examined, computationally. These amino acid functionalized ionic liquids (ILs) are taken into account because of their ability to react with rare earth metal salts. It has been noted that the TSIL with [Br](-) is more soluble than its counterpart TSIL with [NTF2](-), experimentally. In this theoretical work, the combined classical molecular dynamics (CMD) and density functional theory (DFT) calculations are performed to study the behavior of the bulk phase of these two TSILs in the vicinity of water (H2O) molecules with different concentrations. Initially, all the constructed systems are equilibrated using the CMD method. The final structures of the equilibrated systems are extracted for DFT calculations. Under CMD operation, the radial distribution function (RDF) plots and viscosity of TSILs are analyzed to understand the effect of water on TSILs. In the DFT regime, binding energy per H2O, charge transfer, charge density mapping, and electronic density of states (EDOS) analyses are done. The CMD results along with the DFT results are consolidated to support the hydrophilic and hydrophobic nature of the TSILs. Interestingly, we have found a strong correlation between the viscosity and the EDOS results that leads to an understanding of the hydration properties of the TSILs. PMID- 26366530 TI - Quantitative determination of sodium monofluoroacetate "1080" in infant formulas and dairy products by isotope dilution LC-MS/MS. AB - A fast and easy-to-use confirmatory liquid-chromatography tandem mass spectrometry (LC-MS/MS) based-method was developed for the analysis of the pesticide sodium monofluoroacetate (MFA, also called "1080") in infant formulas and related dairy products. Extraction of the compound encompassed sample reconstitution and liquid-liquid extraction under acidic conditions. Time consuming solid-phase extraction steps for clean-up and enrichment and tedious derivatisation were thus avoided. Resulting sample extracts were analysed by electrospray ionisation (ESI) in negative mode. Quantification was performed by the isotopic dilution approach using (13)C-labelled MFA as internal standard. The procedure was validated according to the European document SANCO/12571/2013 and performance parameters such as linearity (r(2) > 0.99), precision (RSD(r) <= 9%, RSD(iR) <= 11%) and recovery (96-117%) fulfilled its requirements. Limit of quantifications (LOQ) was 1 ug kg(-1) for infant formulas and related dairy products except for whey proteins powders with a LOQ of 5 ug kg(-1). Method ruggedness was further assessed in another laboratory devoted to routine testing for quality control. PMID- 26366528 TI - The accumbofrontal tract: Diffusion tensor imaging characterization and developmental change from childhood to adulthood. AB - The presence of an anatomical connection between the orbitofrontal cortex and ventral striatum, forming a so-called reward network, is well established across species. This connection has important implications for reward processing and is relevant to a number of neuropsychiatric disorders. Moreover, white matter (WM) is known to continue to mature across adolescence and into early adulthood, and developmental change in the reward network is an important component of models of decision making and risk taking. Despite the importance of this connection, the underlying WM has only recently been characterized in humans histologically, and not yet in-vivo using brain imaging. Here, we implemented diffusion tensor imaging (DTI) in a large cross-sectional sample of 295 healthy individuals ages 8 68 to further characterize the WM of this connection and its development from childhood into adulthood. We demonstrate that the accumbofrontal tract, connecting the orbitofrontal cortex and nucleus accumbens, can be identified using standard DTI sequences. Using Poisson modeling, we show that the accumbofrontal tract undergoes significant change across the lifespan, with males showing a higher and earlier peak compared to females. Moreover, the change occurs in a pattern consistent with developmental models of decision-making. These findings support the hypothesis that developmental differences in WM integrity may be a contributing factor to the observed risk taking that occurs in adolescence. The accumbofrontal tract is not yet included in standard WM atlases, but may be important for inclusion in studies investigating fronto-striatal networks, as well as in investigations of substance abuse and decision making. PMID- 26366532 TI - Synthesis and characterization of chitosan-g-N-methyl piperazinium chloride: A hybrid flocculant. AB - Flocculation is one of the most widely applied techniques for water treatment. Flocculants based on natural polymer has received more attention due to their eco friendliness in recent years. New water soluble N-methyl piperazinium chloride grafted chitosan flocculant (chitosan-g-N-MPC) was successfully synthesized and thoroughly characterized using FTIR, NMR and powder X-ray diffraction analytical techniques. Incorporation of N-MPC enhanced the ionic character of the chitosan backbone and improved its water solubility. The flocculation performance of chitosan-g-N-MPC was tested against bentonite suspension. The flocculation performance of chitosan-g-N-MPC was investigated under various pH conditions. Turbidity and zeta potential measurements were employed to investigate the flocculation behavior of the chitosan-g-N-MPC. The characteristics of the industrial wastewater before and after flocculation were analyzed. The morphology of the polymer and flocs were studied by TEM analysis. PMID- 26366531 TI - Development of Species-Specific Ah Receptor-Responsive Third Generation CALUX Cell Lines with Enhanced Responsiveness and Improved Detection Limits. AB - The Ah receptor (AhR)-responsive CALUX (chemically activated luciferase expression) cell bioassay is commonly used for rapid screening of samples for the presence of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin), dioxin-like compounds, and AhR agonists/antagonists. By increasing the number of AhR DNA recognition sites (dioxin responsive elements), we previously generated a novel third generation (G3) recombinant AhR-responsive mouse CALUX cell line (H1L7.5c3) with a significantly enhanced response to DLCs compared to existing AhR-CALUX cell bioassays. However, the elevated background luciferase activity of these cells and the absence of comparable G3 cell lines derived from other species have limited their utility for screening purposes. Here, we describe the development and characterization of species-specific G3 recombinant AhR-responsive CALUX cell lines (rat, human, and guinea pig) that exhibit significantly improved limit of detection and dramatically increased TCDD induction response. The low background luciferase activity, low minimal detection limit (0.1 pM TCDD) and enhanced induction response of the rat G3 cell line (H4L7.5c2) over the H1L7.5c3 mouse G3 cells, identifies them as a more optimal cell line for screening purposes. The utility of the new G3 CALUX cell lines were demonstrated by screening sediment extracts and a small chemical compound library for the presence of AhR agonists. The improved limit of detection and increased response of these new G3 CALUX cell lines will facilitate species-specific analysis of DLCs and AhR agonists in samples with low levels of contamination and/or in small sample volumes. PMID- 26366533 TI - Adsorption of methyl orange (MO) by Zr (IV)-immobilized cross-linked chitosan/bentonite composite. AB - A Zr (IV)-immobilized cross-linked chitosan/bentonite composite was synthesized and characterized by Fourier transform infrared, field-emission scanning electron microscopy, and X-ray diffraction techniques. This composite was utilized for the removal of methyl orange (MO) from aqueous solutions. Effects of the loading amount of Zr (IV), initial pH value of MO solutions, adsorbent dosage, and contact time on MO adsorption were considered. The adsorption isotherm data were well described by the Langmuir model, and the maximum adsorption capacity was 438.6mg/g at 303K and natural pH. The kinetic data were well described by the pseudo-second-order model. The thermodynamic data showed that the adsorption process of MO was feasible, spontaneous, and exothermic in nature. PMID- 26366534 TI - Presidential Forum Discussion: Development of Surgical Scientists. PMID- 26366535 TI - Genome-wide Association Study of Postburn Scarring Identifies a Novel Protective Variant. AB - OBJECTIVE: To identify genetic variants associated with the severity of postburn hypertrophic scarring (HTS) using a genome-wide approach. BACKGROUND: Risk of severe postburn HTS is known to depend on race, but the genetic determinants of HTS are unknown. METHODS: We conducted a genome-wide association study (GWAS) in a prospective cohort of adults admitted with deep-partial-thickness burns from 2007 through 2014. Scar severity was assessed over time using the Vancouver Scar Scale (VSS), and DNA was genotyped with a >500,000-marker array. We performed association testing of single-nucleotide polymorphisms (SNPs) with minor allele frequency (MAF) >0.01 using linear regression of VSS height score on genotype adjusted for patient and injury characteristics as well as population genetic structure. Array-wide significance was based on Bonferroni correction for multiple testing. RESULTS: Of 538 patients (median age 40 years, median burn size 6.0% of body surface area), 71% were men and 76% were White. The mean VSS height score was 1.2 (range: 0-3). Of 289,639 SNPs tested, a variant in the CUB and Sushi multiple domains 1 (CSMD1) gene (rs11136645; MAF = 0.49), was significantly associated with decreased scar height (regression coefficient = -0.23, P = 7.9 * 10). CONCLUSIONS: In the first published GWAS of HTS, we report that a common intronic variant in the CSMD1 gene is associated with reduced severity of postburn HTS. If this association is confirmed in an independent cohort, investigating the potential role of CSMD1 in wound healing may elucidate HTS pathophysiology. PMID- 26366536 TI - Overall Survival and Renal Function of Patients With Synchronous Bilateral Wilms Tumor Undergoing Surgery at a Single Institution. AB - OBJECTIVES: Wilms tumor is the most common renal cancer in children. Approximately 5% of children with Wilms tumor present with disease in both kidneys. The treatment challenge is to achieve a high cure rate while maintaining long-term renal function. We retrospectively reviewed our institutional experience with nephron sparing surgery (NSS) in patients with synchronous bilateral Wilms tumor (BWT) operated on between 2001 and 2014. METHODS: Imaging studies, surgical approach, adjuvant therapy, and pathology reports were reviewed. Outcomes evaluated included surgical complications, tumor recurrence, patient survival, and renal function, as assessed by estimated glomerular filtration rate. RESULTS: A total of 42 patients with BWT were identified: 39 (92.9%) patients underwent bilateral NSS; only 3 patients (7.1%) underwent unilateral nephrectomy with contralateral NSS. Postoperative complications included prolonged urine leak (10), infection (6), intussusception (2), and transient renal insufficiency (1). Three patients required early (within 4 months) repeat of NSS for residual tumor. In the long-term, 7 (16.7%) patients had local tumor recurrence (managed with repeat NSS in 6 and completion nephrectomy in 1) and 3 had an episode of intestinal obstruction requiring surgical intervention. Overall survival was 85.7% (mean follow-up, 4.1 years). Of the 6 patients who died, 5 had diffuse anaplastic histology. All of the patients had an estimated glomerular filtration rate more than 60 mL/min/1.73 m at the last follow-up; no patient developed end-stage renal disease. CONCLUSIONS: In patients with synchronous, BWT, bilateral NSS is safe and almost always feasible, thereby preserving maximal renal parenchyma. With this approach, survival was excellent, as was maintenance of the renal function. PMID- 26366537 TI - Prophylactic Inferior Vena Cava Filter Placement Does Not Result in a Survival Benefit for Trauma Patients. AB - OBJECTIVE: Trauma patients are at high risk for life-threatening venous thromboembolic (VTE) events. We examined the relationship between prophylactic inferior vena cava (IVC) filter use, mortality, and VTE. SUMMARY BACKGROUND DATA: The prevalence of prophylactic placement of IVC filters has increased among trauma patients. However, there exists little data on the overall efficacy of prophylactic IVC filters with regard to outcomes. METHODS: Trauma quality collaborative data from 2010 to 2014 were analyzed. Patients were excluded with no signs of life, Injury Severity Score <9, hospitalization <3 days, or who received IVC filter after occurrence of VTE event. Risk-adjusted rates of IVC filter placement were calculated and hospitals placed into quartiles of IVC filter use. Mortality rates by quartile were compared. We also determined the association of deep venous thrombosis (DVT) with the presence of an IVC filter, accounting for type and timing of initiation of pharmacological VTE prophylaxis. RESULTS: A prophylactic IVC filter was placed in 803 (2%) of 39,456 patients. Hospitals exhibited significant variability (0.6% to 9.6%) in adjusted rates of IVC filter utilization. Rates of IVC placement within quartiles were 0.7%, 1.3%, 2.1%, and 4.6%, respectively. IVC filter use quartiles showed no variation in mortality. Adjusting for pharmacological VTE prophylaxis and patient factors, prophylactic IVC filter placement was associated with an increased incidence of DVT (OR = 1.83; 95% CI, 1.15-2.93, P-value = 0.01). CONCLUSIONS: High rates of prophylactic IVC filter placement have no effect on reducing trauma patient mortality and are associated with an increase in DVT events. PMID- 26366538 TI - Autologous Reconstruction and Visceral Transplantation for Management of Patients With Gut Failure After Bariatric Surgery: 20 Years of Experience. AB - OBJECTIVE: Bariatric surgery (BS) is currently the most effective treatment for severe obesity. However, these weight loss procedures may result in the development of gut failure (GF) with the need for total parenteral nutrition (TPN). This retrospective study is the first to address the anatomic and functional spectrum of BS-associated GF with innovative surgical modalities to restore gut function. METHODS: Over 2 decades, 1500 adults with GF were referred with history of BS in 142 (9%). Of these, 131 (92%) were evaluated and received multidisciplinary care. GF was due to catastrophic gut loss (Type-I, 42%), technical complications (Type-II, 33%), and dysfunctional syndromes (Type-III, 25%). Primary bariatric procedures were malabsorptive (5%), restrictive (19%), and combined (76%). TPN duration ranged from 2 to 252 months. RESULTS: Restorative surgery was performed in 116 (89%) patients with utilization of visceral transplantation as a rescue therapy in 23 (20%). With a total of 317 surgical procedures, 198 (62%) were autologous reconstructions; 88 (44%) foregut, 100 (51%) midgut, and 10 (5%) hindgut. An interposition alimentary conduit was used in 7 (6%) patients. Reversal of BS was indicated in 84 (72%) and intestinal lengthening was required in 10 (9%). Cumulative patient survival was 96% at 1 year, 84% at 5 years, and 72% at 15 years. Nutritional autonomy was restored in 83% of current survivors with persistence or relapse of obesity in 23%. CONCLUSIONS: GF is a rare but serious life-threatening complication after BS. Successful outcome is achievable with comprehensive management, including reconstructive surgery and visceral transplantation. PMID- 26366539 TI - The Optical Biopsy: A Novel Technique for Rapid Intraoperative Diagnosis of Primary Pulmonary Adenocarcinomas. AB - BACKGROUND: With increasing use of chest computed tomography scans, indeterminate pulmonary nodules are frequently detected as an incidental finding and present a diagnostic challenge. Tissue biopsy followed by histological review and immunohistochemistry is the gold standard to obtain a diagnosis and the most common malignant finding is a primary lung adenocarcinoma. Our objective was to determine whether an intraoperative optical biopsy (molecular imaging) may provide an alternative approach for determining if a pulmonary nodule is a primary lung adenocarcinoma. METHODS: Before surgery, 30 patients with an indeterminate pulmonary nodule were intravenously administered a folate receptor targeted fluorescent contrast agent specific for primary lung adenocarcinomas. During surgery, the nodule was removed and the presence of fluorescence (optical biopsy) was assessed in the operating room to determine if the nodule was a primary pulmonary adenocarcinoma. Standard-of-care frozen section and immunohistochemical staining on permanent sections were then performed as the gold standard to validate the results of the optical biopsy. RESULTS: Optical biopsies identified 19 of 19 (100%) primary pulmonary adenocarcinomas. There were no false positive or false negative diagnoses. An optical biopsy required 2.4 minutes compared to 26.5 minutes for frozen section (P < 0.001) and it proved more accurate than frozen section in diagnosing lung adenocarcinomas. CONCLUSIONS: An optical biopsy has excellent positive predictive value for intraoperative diagnosis of primary lung adenocarcinomas. With refinement, this technology may prove to be an important supplement to standard pathology for examining close surgical margins, identifying lymph node involvement, and determining whether suspicious nodules are malignant. PMID- 26366540 TI - Factors Predicting Outcomes After a Total Pancreatectomy and Islet Autotransplantation Lessons Learned From Over 500 Cases. AB - OBJECTIVE: Our objective was to analyze factors predicting outcomes after a total pancreatectomy and islet autotransplantation (TP-IAT). BACKGROUND: Chronic pancreatitis (CP) is increasingly treated by a TP-IAT. Postoperative outcomes are generally favorable, but a minority of patients fare poorly. METHODS: In our single-centered study, we analyzed the records of 581 patients with CP who underwent a TP-IAT. Endpoints included persistent postoperative "pancreatic pain" similar to preoperative levels, narcotic use for any reason, and islet graft failure at 1 year. RESULTS: In our patients, the duration (mean +/- SD) of CP before their TP-IAT was 7.1 +/- 0.3 years and narcotic usage of 3.3 +/- 0.2 years. Pediatric patients had better postoperative outcomes. Among adult patients, the odds of narcotic use at 1 year were increased by previous endoscopic retrograde cholangiopancreatography (ERCP) and stent placement, and a high number of previous stents (>3). Independent risk factors for pancreatic pain at 1 year were pancreas divisum, previous body mass index >30, and a high number of previous stents (>3). The strongest independent risk factor for islet graft failure was a low islet yield-in islet equivalents (IEQ)-per kilogram of body weight. We noted a strong dose-response relationship between the lowest-yield category (<2000 IEQ) and the highest (>=5000 IEQ or more). Islet graft failure was 25-fold more likely in the lowest-yield category. CONCLUSIONS: This article represents the largest study of factors predicting outcomes after a TP-IAT. Preoperatively, the patient subgroups we identified warrant further attention. PMID- 26366541 TI - Relationship Between Margin Width and Recurrence of Ductal Carcinoma In Situ: Analysis of 2996 Women Treated With Breast-conserving Surgery for 30 Years. AB - OBJECTIVE: Our goal was to investigate, in a large population of women with ductal carcinoma in situ (DCIS) and long follow-up, the relationship between margin width and recurrence, controlling for other characteristics. BACKGROUND: Although DCIS has minimal mortality, recurrence rates after breast-conserving surgery are significant, and half are invasive. Positive margins are associated with increased risk of local recurrence, but there is no consensus regarding optimal negative margin width. METHODS: We retrospectively reviewed a prospective database of DCIS patients undergoing breast-conserving surgery from 1978 to 2010. Univariate and Cox proportional hazard models were used to investigate the association between margin width and recurrence. RESULTS: In this review, 2996 cases were identified, of which 363 recurred. Median follow-up for women without recurrence was 75 months (range 0-30 years); 732 were studied for >=10 years. Controlling for age, family history, presentation, nuclear grade, number of excisions, radiotherapy (RT), endocrine therapy, and year of surgery, margin width was significantly associated with recurrence in the entire population. Larger negative margins were associated with a lower hazard ratio compared with positive margins. An interaction between RT and margin width was significant (P < 0.03); the association of recurrence with margin width was significant in those without RT (P < 0.0001), but not in those with RT (P = 0.95). CONCLUSIONS: In women not receiving RT, wider margins are significantly associated with a lower rate of recurrence. Obtaining wider negative margins may be important in reducing the risk of recurrence in women who choose not to undergo RT and may not be necessary in those who receive RT. PMID- 26366542 TI - Sarcoma Resection With and Without Vascular Reconstruction: A Matched Case control Study. AB - OBJECTIVE: To examine the impact of major vascular resection on sarcoma resection outcomes. SUMMARY BACKGROUND DATA: En bloc resection and reconstruction of involved vessels is being increasingly performed during sarcoma surgery; however, the perioperative and oncologic outcomes of this strategy are not well described. METHODS: Patients undergoing sarcoma resection with (VASC) and without (NO-VASC) vascular reconstruction were 1:2 matched on anatomic site, histology, grade, size, synchronous metastasis, and primary (vs. repeat) resection. R2 resections were excluded. Endpoints included perioperative morbidity, mortality, local recurrence, and survival. RESULTS: From 2000 to 2014, 50 sarcoma patients underwent VASC resection. These were matched with 100 NO-VASC patients having similar clinicopathologic characteristics. The rates of any complication (74% vs. 44%, P = 0.002), grade 3 or higher complication (38% vs. 18%, P = 0.024), and transfusion (66% vs. 33%, P < 0.001) were all more common in the VASC group. Thirty-day (2% vs. 0%, P = 0.30) or 90-day mortality (6% vs. 2%, P = 0.24) were not significantly higher. Local recurrence (5-year, 51% vs. 54%, P = 0.11) and overall survival after resection (5-year, 59% vs. 53%, P = 0.67) were similar between the 2 groups. Within the VASC group, overall survival was not affected by the type of vessel involved (artery vs. vein) or the presence of histology-proven vessel wall invasion. CONCLUSIONS: Vascular resection and reconstruction during sarcoma resection significantly increases perioperative morbidity and requires meticulous preoperative multidisciplinary planning. However, the oncologic outcome appears equivalent to cases without major vascular involvement. The anticipated need for vascular resection and reconstruction should not be a contraindication to sarcoma resection. PMID- 26366543 TI - Management of the Parathyroid Glands During Preventive Thyroidectomy in Patients With Multiple Endocrine Neoplasia Type 2. AB - OBJECTIVES: Patients with multiple endocrine neoplasia type 2 (MEN2) have mutations in the RET protooncogene and virtually all of them will develop medullary thyroid carcinoma. Family members identified by genetic testing are candidates for preventive thyroidectomy. Management of the parathyroids during thyroidectomy is controversial. Some experts advocate total parathyroidectomy with autotransplantation, whereas others recommend preserving the parathyroids in situ. METHODS: Between 1993 and 2000, we performed preventive thyroidectomies on 50 patients with MEN2A (group A). All patients had a central neck dissection (CND) combined with total parathyroidectomy and autotransplantation of parathyroid slivers to the nondominant forearm or to the neck. Between 2003 and the present, we performed 102 preventive thyroidectomies attempting to preserve the parathyroid glands in situ with an intact vascular pedicle (group B). Individual parathyroids were autotransplanted only if they appeared nonviable or could not be preserved intact. Central neck dissection was done only if the serum calcitonin was greater than 40 pg/mL. RESULTS: Permanent hypoparathyroidism occurred in 3 (6%) of 50 patients in group A, compared with 1 (1%) of 102 patients in group B (P = 0.1). After total thyroidectomy, no patient in either group developed permanent recurrent laryngeal nerve injury or hyperparathyroidism. Immediate postoperative serum calcitonin levels were in the normal range (<5 pg/mL) in 100 of 102 patients in group B. No patients in either group have died. Oncologic follow-up of patients in group B is in progress. CONCLUSIONS: In patients with MEN2A treated by preventive total thyroidectomy routine total parathyroidectomy with autotransplantation and CND gives excellent long-term results. However, preservation of the parathyroids in situ during preventive thyroidectomy combined with selective CND based on preoperative basal serum calcitonin levels is an effective and safe alternative that results in a very low incidence of hypoparathyroidism. PMID- 26366544 TI - Use of a Bundle Checklist Combined With Physician Confirmation Reduces Risk of Nosocomial Complications and Death in Trauma Patients Compared to Documented Checklist Use Alone. AB - BACKGROUND: Bundle checklists are increasingly utilized in patient care, but data are inconsistent regarding their efficacy in reducing nosocomial complication rates. We examined whether checklist usage was associated with nosocomial complications; when documented, elements were verified by provider bedside rounds. METHODS: We performed a retrospective cohort study of trauma patients admitted to our hospital during a three-phase implementation of a quality improvement project. For this analysis, patients were categorized under predocumentation (PD), documentation only (DO), or documentation with provider review (PR) cohort based on temporal designations. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between documentation cohorts and nosocomial complications. RESULTS: No difference was observed in mean hospital stay, intensive care unit (ICU) days, or ventilator days. The DO cohort showed no significant differences in the risk of complications. Among ICU patients, when compared with the PD cohort, the PR cohort demonstrated a decreased risk of all complications OR 0.72 (95% CI 0.55 0.93), pulmonary embolus OR 0.29 (95% CI 0.11-0.73), pneumonia OR 0.66 (95% CI 0.50-0.88), and death OR 0.50 (95% CI 0.31-0.79). CONCLUSIONS: Bedside confirmation of bundle checklists during physician extender rounds reduces the risk of pulmonary embolus, pneumonia, and death when compared to chart documentation alone. This study underscores the importance of the team approach to the bundle checklist and it's ability to reduce morbidity and mortality. PMID- 26366545 TI - How Well Does Renal Transplantation Cure Hyperparathyroidism? AB - BACKGROUND: Most patients with end-stage renal disease will develop hyperparathyroidism (HPT). Transplantation reportedly resolves HPT in most cases. Currently, guidelines recommend a watchful waiting approach to HPT for the first 12 months after the transplantation to allow maximal allograft function. The purpose of our study is to examine the incidence and impact of HPT, defined as an elevated parathyroid hormone (PTH) level, after renal transplantation in a contemporary cohort. METHODS: Primary kidney transplantation was performed on 1609 patients from January 1, 2004, to June 6, 2012. Patients were stratified by timing of achieving normal serum PTH levels, and a multivariate logistic regression was constructed to determine predictive variables. Kaplan-Meier analysis was then performed on overall graft survival based on PTH normalization. RESULTS: Four hundred eighty-eight (30.3%) patients achieved normal PTH within 1 year posttransplant. Four hundred twenty-seven (26.6%) attained normal PTH between 1 and 2 years, with the remaining 694 (43.1%) categorized as having HPT. Patients achieving normal PTH within 12 months of transplantation had a significantly longer median graft survival (7.33 years) compared with those patients who normalized between 12 and 24 months (4.92 years, P < 0.001), and those with HPT (5.13 years, P < 0.001). Comparing normalization of PTH by 2 years to HPT patients, obesity (P < 0.001), months on dialysis (P < 0.001), and delayed graft failure (P = 0.006) were predictive of nonnormalization. Overall, allograft survival analysis revealed a survival advantage for patients who normalize PTH within 24 months of transplantation (P = 0.038). CONCLUSIONS: Renal transplant resolves HPT in 56.9% of patients at 2 years. Resolution within the first year portends longer graft survival. Therefore, earlier intervention for HPT should be considered. PMID- 26366546 TI - A Quarter Century of Organ Protection in Open Thoracoabdominal Repair. AB - INTRODUCTION: Thoracoabdominal aortic aneurysm (TAAA) remains a challenging problem. We sought to examine our experience with thoracic and thoracoabdominal aortic repairs over a 24-year period. METHODS: Patient information was collected in a prospective database and analyzed retrospectively. Univariate and multivariable analysis was performed. RESULTS: Between January 1991 and December 2014, we repaired 1896 descending thoracic (DTAA) or TAAA in 1795 patients. Mean age was 64.2 +/- 13.8, and 702 (37%) were women. Of 1896 operations, 646 (34.1%) were DTAA, 316 (16.7%) TAAA extent I, 310 (16.4%) TAAA extent II, 187 (9.9%) TAAA extent III, 348 (18.4%) TAAA extent IV, and 112 (5.9%) TAAA extent V. Adjunct [cerebrospinal fluid drainage (CSFD) + distal aortic perfusion (DAP)] was used in 78.4%. Mean preoperative glomerular filtration rate (GFR) was 75.1 +/- 14.9 mL/min/1.73 m. Renal dysfunction occurred in 461 (24.3%). Immediate neurodeficit (IND) occurred in 79 (4.2%) and delayed in 104 (5.5%). Of these, 47/104 (45%) recovered by discharge. Postoperative stroke was 95/1896 (5%). Early mortality was 302/1896 (15.9%). Mortality with GFR >95.3 was 28/457 (6.1%), and 131/432 (30.3%) was with GFR < 48.3 (P < 0.0001). Predictors of early mortality were age (P < 0.02), GFR (P < 0.0001), TAAA2 or 3 (P = 0.001), coronary artery disease (P = 0.001), and emergency (P < 0.0001). CONCLUSIONS: Open DTAA and TAAA repair can be performed with acceptable early and late outcomes. This study provides important early- and long-term data on open repair, allowing for better risk stratification of patients with DTAA and TAAA. It is the high-risk subgroup that can now be targeted for endovascular techniques. PMID- 26366547 TI - Racial Disparity in Renal Transplantation: Alemtuzumab the Great Equalizer? AB - OBJECTIVES: Racial disparity as a barrier to successful outcomes in renal transplants for African Americans has been well described. Numerous unsuccessful attempts have been made to identify specific immunologic and socioeconomic factors. The objective of our study was to determine whether alemtuzumab (AL) induction abolishes this discrepancy and improves allograft survival in African American recipients. METHODS: A retrospective chart review of consecutive adult renal transplants was conducted between 2006 and 2014. Kaplan-Meier analysis and hazard ratios were calculated for the African Americans (AA) and white groups. Multiple linear regressions were performed to assess independent variables (race, retransplant, sex, donor type, induction agent) on allograft survival. RESULTS: A significant difference in allograft survival was identified between whites (n = 272) and AA (n = 445), with AA experiencing more graft losses (18.2% vs 12.1%, P = 0.0351). Induction with AL improved outcomes in all transplant recipients. Multiple linear regression identified that the strongest predictor of allograft failure was induction without AL (P < 0.0001). The data for a subset analysis matched for follow-up length demonstrated that whites compared with AA (n = 157, 67 whites and 90 AA) had lower rates of allograft failure in the absence of AL induction (14.9% vs 44.4%, P = 0.0156, hazard ratio = 2.077). In contrast, AL induction (n = 275, 105 whites and 170 AA) eliminated the racial disparity in allograft failure (5.7% vs 9.4%, P = 0.8248, hazard ratio = 1.504). CONCLUSIONS: This is the first study to describe the effects of AL induction therapy on AA renal transplant recipients beyond the first posttransplant year. Our early results suggest that AL induction therapy abolishes the disparity in renal allograft failure. PMID- 26366548 TI - Transabdominal Redo Ileal Pouch Surgery for Failed Restorative Proctocolectomy: Lessons Learned Over 500 Patients. AB - OBJECTIVES: The purpose of this study was to report our large, single-center experience of transabdominal ileal pouch-anal anastomoses (IPAA) redo surgery for a failed initial IPAA. BACKGROUND: IPAA fail from 3% to 15% of the times, mainly due to technical or inflammatory conditions. There is limited information about the surgical, functional, and quality-of-life (QOL) outcomes of redo surgery for failed IPAA, especially in large series of patients. METHODS: Patients undergoing transabdominal redo surgery for failed IPAA between 1983 and 2014 were evaluated. Primary endpoints were morbidity of the surgery, the proportion of patients with a functioning pouch, frequency of defecation and incidence of incontinence, and the patients' perception of QOL. RESULTS: There were 502 (43% males) patients with a median age of 38 years and median body mass index 24 kg/m at the time of revision surgery. A new pouch was created in 41% of patients whereas 59% had their original pouch revised and retained. Postoperative mortality was 0% and morbidity was 53%. The short-term anastomotic leak rate was 8%. At a median follow-up of 7 years after redo surgery, 101 (n = 20%) patients had redo IPAA failure. Pelvic sepsis developing after redo ileal pouch surgery was the primary indicator of pouch failure (hazard ratio, 3.691; 95% confidence interval, 2.411 5.699; P < 0.0001). Overall functional outcomes and QOL scores were acceptable. CONCLUSIONS: Patients with a failed ileoanal pouch may be offered redo pouch surgery with a high likelihood of success in terms of function and QOL. PMID- 26366550 TI - A Longitudinal Assessment of Outcomes and Healthcare Resource Utilization After Immediate Breast Reconstruction-Comparing Implant- and Autologous-based Breast Reconstruction. AB - OBJECTIVES: Immediate breast reconstruction (IBR) after mastectomy for cancer has increased in recent years, yet long-term, modality-specific comparative data are lacking. We performed this study to compare short- and long-term outcomes after expander, autologous (AT), and direct-to-implant (DI) breast reconstruction. METHODS: Using four state-level inpatient and ambulatory surgery databases, we conducted a retrospective cohort study of adult women who underwent mastectomy with immediate breast reconstruction from 2008 to 2009. Our primary outcomes were complications within 90 days of surgery, rate of secondary breast surgery within 3 years, and cumulative healthcare charges. RESULTS: The final cohort included 15,154 women who underwent mastectomy with tissue expander (TE: 70.5%), autologous (AT: 18.1%), or direct to implant (DI: 11.3%) reconstruction. Ninety day complications were lowest after expander and highest after AT breast reconstruction (TE = 6.5% [reference] vs AT = 13.1% [2.09, 1.82-2.41] vs DI = 6.6% [1.03, 0.84-1.27], P < 0.001). However, adjusted rates of secondary breast procedures were most frequent after expander (2021/1000 discharges) and least frequent after AT (949.0/1000 discharges) reconstruction (P < 0.001). Specifically, unplanned revisions were highest among the tissue expander cohort (TE = 59.2% vs AT = 34.4% vs DI = 45.9%, P < 0.001). The cumulative, adjusted healthcare charges for secondary breast procedures differed slightly across groups (TE = $63,806 vs AT = $66,882 vs DI = $64,145, P < 0.001). CONCLUSIONS: Complications and secondary breast procedures, including unplanned revisions, after breast reconstruction are common and vary by reconstructive modality. The frequency of these secondary procedures adds substantial healthcare charges to the care of the breast reconstruction patient. PMID- 26366549 TI - Components of Hospital Perioperative Infrastructure Can Overcome the Weekend Effect in Urgent General Surgery Procedures. AB - OBJECTIVE: We hypothesized that perioperative hospital resources could overcome the "weekend effect" (WE) in patients undergoing emergent/urgent surgeries. SUMMARY BACKGROUND DATA: The WE is the observation that surgeon-independent patient outcomes are worse on the weekend compared with weekdays. The WE is often explained by differences in staffing and resources resulting in variation in care between the week and weekend. METHODS: Emergent/urgent surgeries were identified using the Healthcare Cost and Utilization Project State Inpatient Database (Florida) from 2007 to 2011 and linked to the American Hospital Association (AHA) Annual Survey Database to determine hospital level characteristics. Extended median length of stay (LOS) on the weekend compared with the weekdays (after controlling for hospital, year, and procedure type) was selected as a surrogate for WE. RESULTS: Included were 126,666 patients at 166 hospitals. A total of 17 hospitals overcame the WE during the study period. Logistic regression, controlling for patient characteristics, identified full adoption of electronic medical records (OR 4.74), home health program (OR 2.37), pain management program [odds ratio (OR) 1.48)], increased registered nurse-to-bed ratio (OR 1.44), and inpatient physical rehabilitation (OR 1.03) as resources that were predictors for overcoming the WE. The prevalence of these factors in hospitals exhibiting the WE for all 5 years of the study period were compared with those hospitals that overcame the WE (P < 0.001). CONCLUSIONS: Specific hospital resources can overcome the WE seen in urgent general surgery procedures. Improved hospital perioperative infrastructure represents an important target for overcoming disparities in surgical care. PMID- 26366551 TI - Height-reducing variants and selection for short stature in Sardinia. AB - We report sequencing-based whole-genome association analyses to evaluate the impact of rare and founder variants on stature in 6,307 individuals on the island of Sardinia. We identify two variants with large effects. One variant, which introduces a stop codon in the GHR gene, is relatively frequent in Sardinia (0.87% versus <0.01% elsewhere) and in the homozygous state causes Laron syndrome involving short stature. We find that this variant reduces height in heterozygotes by an average of 4.2 cm (-0.64 s.d.). The other variant, in the imprinted KCNQ1 gene (minor allele frequency (MAF) = 7.7% in Sardinia versus <1% elsewhere) reduces height by an average of 1.83 cm (-0.31 s.d.) when maternally inherited. Additionally, polygenic scores indicate that known height-decreasing alleles are at systematically higher frequencies in Sardinians than would be expected by genetic drift. The findings are consistent with selection for shorter stature in Sardinia and a suggestive human example of the proposed 'island effect' reducing the size of large mammals. PMID- 26366552 TI - Population genetic differentiation of height and body mass index across Europe. AB - Across-nation differences in the mean values for complex traits are common, but the reasons for these differences are unknown. Here we find that many independent loci contribute to population genetic differences in height and body mass index (BMI) in 9,416 individuals across 14 European countries. Using discovery data on over 250,000 individuals and unbiased effect size estimates from 17,500 sibling pairs, we estimate that 24% (95% credible interval (CI) = 9%, 41%) and 8% (95% CI = 4%, 16%) of the captured additive genetic variance for height and BMI, respectively, reflect population genetic differences. Population genetic divergence differed significantly from that in a null model (height, P < 3.94 * 10(-8); BMI, P < 5.95 * 10(-4)), and we find an among-population genetic correlation for tall and slender individuals (r = -0.80, 95% CI = -0.95, -0.60), consistent with correlated selection for both phenotypes. Observed differences in height among populations reflected the predicted genetic means (r = 0.51; P < 0.001), but environmental differences across Europe masked genetic differentiation for BMI (P < 0.58). PMID- 26366553 TI - Genome-wide association analyses based on whole-genome sequencing in Sardinia provide insights into regulation of hemoglobin levels. AB - We report genome-wide association study results for the levels of A1, A2 and fetal hemoglobins, analyzed for the first time concurrently. Integrating high density array genotyping and whole-genome sequencing in a large general population cohort from Sardinia, we detected 23 associations at 10 loci. Five signals are due to variants at previously undetected loci: MPHOSPH9, PLTP-PCIF1, ZFPM1 (FOG1), NFIX and CCND3. Among the signals at known loci, ten are new lead variants and four are new independent signals. Half of all variants also showed pleiotropic associations with different hemoglobins, which further corroborated some of the detected associations and identified features of coordinated hemoglobin species production. PMID- 26366555 TI - Mammalian pre-implantation chromosomal instability: species comparison, evolutionary considerations, and pathological correlations. AB - Pre-implantation embryo development in mammals begins at fertilization with the migration and fusion of the maternal and paternal pro-nuclei, followed by the degradation of inherited factors involved in germ cell specification and the activation of embryonic genes required for subsequent cell divisions, compaction, and blastulation. The majority of studies on early embryogenesis have been conducted in the mouse or non-mammalian species, often requiring extrapolation of the findings to human development. Given both conserved similarities and species specific differences, however, even comparison between closely related mammalian species may be challenging as certain aspects, including susceptibility to chromosomal aberrations, varies considerably across mammals. Moreover, most human embryo studies are limited to patient samples obtained from in vitro fertilization (IVF) clinics and donated for research, which are generally of poorer quality and produced with germ cells that may be sub-optimal. Recent technical advances in genetic, epigenetic, chromosomal, and time-lapse imaging analyses of high quality whole human embryos have greatly improved our understanding of early human embryogenesis, particularly at the single embryo and cell level. This review summarizes the major characteristics of mammalian pre implantation development from a chromosomal perspective, in addition to discussing the technological achievements that have recently been developed to obtain this data. We also discuss potential translation to clinical applications in reproductive medicine and conclude by examining the broader implications of these findings for the evolution of mammalian species and cancer pathology in somatic cells. PMID- 26366554 TI - Genome sequencing elucidates Sardinian genetic architecture and augments association analyses for lipid and blood inflammatory markers. AB - We report ~17.6 million genetic variants from whole-genome sequencing of 2,120 Sardinians; 22% are absent from previous sequencing-based compilations and are enriched for predicted functional consequences. Furthermore, ~76,000 variants common in our sample (frequency >5%) are rare elsewhere (<0.5% in the 1000 Genomes Project). We assessed the impact of these variants on circulating lipid levels and five inflammatory biomarkers. We observe 14 signals, including 2 major new loci, for lipid levels and 19 signals, including 2 new loci, for inflammatory markers. The new associations would have been missed in analyses based on 1000 Genomes Project data, underlining the advantages of large-scale sequencing in this founder population. PMID- 26366557 TI - Clinical Validation of Targeted Next Generation Sequencing for Colon and Lung Cancers. AB - OBJECTIVE: Recently, Next Generation Sequencing (NGS) has begun to supplant other technologies for gene mutation testing that is now required for targeted therapies. However, transfer of NGS technology to clinical daily practice requires validation. METHODS: We validated the Ion Torrent AmpliSeq Colon and Lung cancer panel interrogating 1850 hotspots in 22 genes using the Ion Torrent Personal Genome Machine. First, we used commercial reference standards that carry mutations at defined allelic frequency (AF). Then, 51 colorectal adenocarcinomas (CRC) and 39 non small cell lung carcinomas (NSCLC) were retrospectively analyzed. RESULTS: Sensitivity and accuracy for detecting variants at an AF >4% was 100% for commercial reference standards. Among the 90 cases, 89 (98.9%) were successfully sequenced. Among the 86 samples for which NGS and the reference test were both informative, 83 showed concordant results between NGS and the reference test; i.e. KRAS and BRAF for CRC and EGFR for NSCLC, with the 3 discordant cases each characterized by an AF <10%. CONCLUSIONS: Overall, the AmpliSeq colon/lung cancer panel was specific and sensitive for mutation analysis of gene panels and can be incorporated into clinical daily practice. PMID- 26366556 TI - Fission Yeast CSL Transcription Factors: Mapping Their Target Genes and Biological Roles. AB - BACKGROUND: Cbf11 and Cbf12, the fission yeast CSL transcription factors, have been implicated in the regulation of cell-cycle progression, but no specific roles have been described and their target genes have been only partially mapped. METHODOLOGY/PRINCIPAL FINDINGS: Using a combination of transcriptome profiling under various conditions and genome-wide analysis of CSL-DNA interactions, we identify genes regulated directly and indirectly by CSL proteins in fission yeast. We show that the expression of stress-response genes and genes that are expressed periodically during the cell cycle is deregulated upon genetic manipulation of cbf11 and/or cbf12. Accordingly, the coordination of mitosis and cytokinesis is perturbed in cells with genetically manipulated CSL protein levels, together with other specific defects in cell-cycle progression. Cbf11 activity is nutrient-dependent and Deltacbf11-associated defects are mitigated by inactivation of the protein kinase A (Pka1) and stress-activated MAP kinase (Sty1p38) pathways. Furthermore, Cbf11 directly regulates a set of lipid metabolism genes and Deltacbf11 cells feature a stark decrease in the number of storage lipid droplets. CONCLUSIONS/SIGNIFICANCE: Our results provide a framework for a more detailed understanding of the role of CSL proteins in the regulation of cell-cycle progression in fission yeast. PMID- 26366558 TI - Fitness Benefits of Mate Choice for Compatibility in a Socially Monogamous Species. AB - Research on mate choice has primarily focused on preferences for quality indicators, assuming that all individuals show consensus about who is the most attractive. However, in some species, mating preferences seem largely individual specific, suggesting that they might target genetic or behavioral compatibility. Few studies have quantified the fitness consequences of allowing versus preventing such idiosyncratic mate choice. Here, we report on an experiment that controls for variation in overall partner quality and show that zebra finch (Taeniopygia guttata) pairs that resulted from free mate choice achieved a 37% higher reproductive success than pairs that were forced to mate. Cross-fostering of freshly laid eggs showed that embryo mortality (before hatching) primarily depended on the identity of the genetic parents, whereas offspring mortality during the rearing period depended on foster-parent identity. Therefore, preventing mate choice should lead to an increase in embryo mortality if mate choice targets genetic compatibility (for embryo viability), and to an increase in offspring mortality if mate choice targets behavioral compatibility (for better rearing). We found that pairs from both treatments showed equal rates of embryo mortality, but chosen pairs were better at raising offspring. These results thus support the behavioral, but not the genetic, compatibility hypothesis. Further exploratory analyses reveal several differences in behavior and fitness components between "free-choice" and "forced" pairs. PMID- 26366561 TI - Understanding Microbiome Data: A Primer for Clinicians. AB - The human gut contains 1014 bacteria and many other micro-organisms such as Archaea, viruses and fungi. This gut microbiota has co-evolved with host determinants through symbiotic and co-dependent relationships. Bacteria, which represent 10 times the number of human cells, form the most depicted part of this black box owing to new tools. Re-evaluating the gut microbiota showed how this entity participates in gut physiology and beyond this in human health. Studying and handling this real 'hidden organ' remains a challenge for clinicians. In this review, we aimed to bring information about gut microbiota, its structure, its roles and the way to capture and measure it. After bacterial colonization in infant, intestinal microbial composition is unique for each individual although more than 95% can be assigned to 4 major phyla. Besides its biodiversity, the major characteristics of gut microbiota are stability over time and resilience after perturbation. In pathological situations, dysbiosis (i.e. imbalance in gut microbiota composition) is observed with a loss in overall diversity. Dysbiosis associated with inflammatory bowel disease was specified with the reduction in biodiversity, the decreased representation of different taxa in the Firmicutes phylum and an increase in Gammaproteobacteria. Beyond depicting gut microbial composition, metagenomics allows the description of the combined genomes of the microorganisms present in the gut, giving access to their potential functions. In fact, each individual overall microbial metagenome outnumbers the size of human genome by a factor of 150. Besides a functional core in which there is redundancy for mandatory functions assuring the robustness of the ecosystem, human gut contains an important diversity and high number of non-redundant bacterial genes. Clinical data, treatment and all the factors able to influence microbiome should enter integrated big data sets to put in light pathways of interplay within the supra organism composed of gut microbiome and host. A better understanding of dynamics within human gut microbiota and microbes-host interaction will allow new insight into gut pathophysiology especially regarding resilience mechanisms and dysbiosis onset and maintenance. This will lead to description of biomarkers of diseases, development of new probiotics/prebiotics and new therapies. PMID- 26366559 TI - Influence of Sex on Suicidal Phenotypes in Affective Disorder Patients with Traumatic Childhood Experiences. AB - OBJECTIVES: In the current study, we aimed to investigate the impact of childhood trauma on suicidal behaviour phenotypes in a group of patients with diagnosed affective disorder (unipolar or bipolar affective disorder). PATIENTS AND METHODS: Patients with and without a history of childhood abuse, measured by Childhood Trauma Questionnaire (CTQ), were assessed to explore risks for suicidal behaviour (including suicide attempt, self-harm and non-suicidal self-injury). The tested sample consisted of 258 patients (111 males and 147 females, in patients and out-patients at the Department of Psychiatry and Psychotherapy, Medical University of Vienna and University Hospital Tulln, Lower Austria). Psychiatric diagnoses were derived from the SCAN (Schedules for Clinical Assessment in Neuropsychiatry) interview. In addition, patients were administered the Lifetime Parasuicidal Count (LPC), Suicidal Behaviour Questionnaire (SBQ-R), and Viennese Suicide Risk Assessment Scale (VISURIAS) questionnaires. RESULTS: In contrast to male suicide attempters, female suicide attempters showed both significantly higher total CTQ scores (p<0.001), and higher CTQ subscores (emotional, physical and sexual abuse, as well as emotional and physical neglect) in comparison to the non-suicidal control group. Besides, females with a history of self-harming behaviour (including suicidal intention) and Non-Suicidal-Self Injury (NSSI) had significantly higher CTQ total scores (p<0.001) than the control group. CONCLUSION: These findings suggest gender differences in suicidal behaviour after being exposed to childhood trauma. PMID- 26366560 TI - RhoGAP18B Isoforms Act on Distinct Rho-Family GTPases and Regulate Behavioral Responses to Alcohol via Cofilin. AB - Responses to the effects of ethanol are highly conserved across organisms, with reduced responses to the sedating effects of ethanol being predictive of increased risk for human alcohol dependence. Previously, we described that regulators of actin dynamics, such as the Rho-family GTPases Rac1, Rho1, and Cdc42, alter Drosophila's sensitivity to ethanol-induced sedation. The GTPase activating protein RhoGAP18B also affects sensitivity to ethanol. To better understand how different RhoGAP18B isoforms affect ethanol sedation, we examined them for their effects on cell shape, GTP-loading of Rho-family GTPase, activation of the actin-severing cofilin, and actin filamentation. Our results suggest that the RhoGAP18B-PA isoform acts on Cdc42, while PC and PD act via Rac1 and Rho1 to activate cofilin. In vivo, a loss-of-function mutation in the cofilin encoding gene twinstar leads to reduced ethanol-sensitivity and acts in concert with RhoGAP18B. Different RhoGAP18B isoforms, therefore, act on distinct subsets of Rho-family GTPases to modulate cofilin activity, actin dynamics, and ethanol induced behaviors. PMID- 26366562 TI - Absolute Reticulocyte Count Acts as a Surrogate for Fetal Hemoglobin in Infants and Children with Sickle Cell Anemia. AB - Hemoglobin switching is largely complete in humans by six months of age. Among infants with sickle cell anemia (HbSS, SCA), reticulocytosis begins early in life as fetal hemoglobin (HbF) is replaced by sickle hemoglobin (HbS). The objective of this study was to determine if absolute reticulocyte count (ARC) is related to HbF levels in a cohort of pediatric SCA patients. A convenience sample of 106 children with SCA between the ages of 1 month and 20 years who were not receiving hydroxyurea or monthly blood transfusions were enrolled in this observational study. Hematologic data, including ARC and HbF levels, were measured at steady state. F-cells were enumerated by flow cytometry. Initial studies compared infants with ARC greater than or equal to 200 K/MUL (ARC >= 200) based upon the previously reported utility of this threshold as a predictive marker for SCA severity. Mean HbF and F-cell levels were significantly lower in the ARC >= 200 group when compared to the ARC < 200 group. Both HbF and F-cell percentages were negatively correlated to ARC in infants and in children between the ages of 1 and 9 years. However, the inverse relationship was lost after the age of 10 years. Overall, decreased expression and distribution of HbF during childhood SCA is well-correlated with increased reticulocyte production and release into the peripheral blood. As such, these data further support the clinical use of reticulocyte enumeration as a disease severity biomarker for childhood sickle cell anemia. PMID- 26366563 TI - Seeing Touches Early in Life. AB - The sense of touch provides fundamental information about the surrounding world, and feedback about our own actions. Although touch is very important during the earliest stages of life, to date no study has investigated infants' abilities to process visual stimuli implying touch. This study explores the developmental origins of the ability to visually recognize touching gestures involving others. Looking times and orienting responses were measured in a visual preference task, in which participants were simultaneously presented with two videos depicting a touching and a no-touching gesture involving human body parts (face, hand) and/or an object (spoon). In Experiment 1, 2-day-old newborns and 3-month-old infants viewed two videos: in one video a moving hand touched a static face, in the other the moving hand stopped before touching it. Results showed that only 3-month olds, but not newborns, differentiated the touching from the no-touching gesture, displaying a preference for the former over the latter. To test whether newborns could manifest a preferential visual response when the touched body part is different from the face, in Experiment 2 newborns were presented with touching/no touching gestures in which a hand or an inanimate object-i.e., a spoon- moved towards a static hand. Newborns were able to discriminate a hand-to-hand touching gesture, but they did not manifest any preference for the object-to-hand touch. The present findings speak in favour of an early ability to visually recognize touching gestures involving the interaction between human body parts. PMID- 26366564 TI - Impacts of Satellite-Based Snow Albedo Assimilation on Offline and Coupled Land Surface Model Simulations. AB - Seasonal snow cover in the Northern Hemisphere is the largest component of the terrestrial cryosphere and plays a major role in the climate system through strong positive feedbacks related to albedo. The snow-albedo feedback is invoked as an important cause for the polar amplification of ongoing and projected climate change, and its parameterization across models is an important source of uncertainty in climate simulations. Here, instead of developing a physical snow albedo scheme, we use a direct insertion approach to assimilate satellite-based surface albedo during the snow season (hereafter as snow albedo assimilation) into the land surface model ORCHIDEE (ORganizing Carbon and Hydrology In Dynamic EcosystEms) and assess the influences of such assimilation on offline and coupled simulations. Our results have shown that snow albedo assimilation in both ORCHIDEE and ORCHIDEE-LMDZ (a general circulation model of Laboratoire de Meteorologie Dynamique) improve the simulation accuracy of mean seasonal (October throughout May) snow water equivalent over the region north of 40 degrees. The sensitivity of snow water equivalent to snow albedo assimilation is more pronounced in the coupled simulation than the offline simulation since the feedback of albedo on air temperature is allowed in ORCHIDEE-LMDZ. We have also shown that simulations of air temperature at 2 meters in ORCHIDEE-LMDZ due to snow albedo assimilation are significantly improved during the spring in particular over the eastern Siberia region. This is a result of the fact that high amounts of shortwave radiation during the spring can maximize its snow albedo feedback, which is also supported by the finding that the spatial sensitivity of temperature change to albedo change is much larger during the spring than during the autumn and winter. In addition, the radiative forcing at the top of the atmosphere induced by snow albedo assimilation during the spring is estimated to be -2.50 W m-2, the magnitude of which is almost comparable to that due to CO2 (2.83 W m-2) increases since 1750. Our results thus highlight the necessity of realistic representation of snow albedo in the model and demonstrate the use of satellite-based snow albedo to improve model behaviors, which opens new avenues for constraining snow albedo feedback in earth system models. PMID- 26366566 TI - Bilateral Vestibular Hypofunction: Challenges in Establishing the Diagnosis in Adults. AB - Bilateral vestibular hypofunction (BVH) probably represents a heterogeneous disorder with different types of clinical pictures, with and without vertigo. In spite of increasingly sophisticated electrophysiological testing, still many challenges are met when establishing a diagnosis of BVH. Here, we review the main challenges, which are a reflection of its often difficult clinical presentation and the lack of diagnostic standards regarding the implementation and interpretation of vestibular tests. These challenges show that there is an urgent need for standardization. The resulting decisions should be used for the development of uniform diagnostic criteria for BVH, which are, at present, not yet available. PMID- 26366565 TI - A Genome-Wide mRNA Screen and Functional Analysis Reveal FOXO3 as a Candidate Gene for Chicken Growth. AB - Chicken growth performance provides direct economic benefits to the poultry industry. However, the underlying genetic mechanisms are unclear. The objective of this study was to identify candidate genes associated with chicken growth and investigate their potential mechanisms. We used RNA-Seq to study the breast muscle transcriptome in high and low tails of Recessive White Rock (WRRh, WRRl) and Xinghua chickens (XHh, XHl). A total of 60, 23, 153 and 359 differentially expressed genes were detected in WRRh vs. WRRl, XHh vs. XHl, WRRh vs. XHh and WRRl vs. XHl, respectively. GO, KEGG pathway and gene network analyses showed that CEBPB, FBXO32, FOXO3 and MYOD1 played key roles in growth. The functions of FBXO32 and FOXO3 were validated. FBXO32 was predominantly expressed in leg muscle, heart and breast muscle. After decreased FBXO32 expression, growth related genes such as PDK4, IGF2R and IGF2BP3 were significantly down-regulated (P < 0.05). FBXO32 was significantly (P < 0.05) associated with carcass and meat quality traits, but not growth traits. FOXO3 was predominantly expressed in breast and leg muscle. In both of these tissues, the FOXO3 mRNA level in XH was significantly higher than that in WRR chickens with normal body weight (P < 0.05). In DF-1 cells, siRNA knockdown of FOXO3 significantly (P < 0.01) inhibited the MYOD expression and significantly up-regulated (P < 0.01 or P < 0.05) the expression of growth-related genes including CEBPB, FBXO32, GH, GHR, IGF1R, IGF2R, IGF2BP1, IGF2BP3, INSR, PDK1 and PDK4. Moreover, 18 SNPs were identified in FOXO3. G66716193A was significantly (P < 0.05) associated with growth traits. The sites C66716002T, C66716195T and A66716179G were significantly (P < 0.05) associated with growth or carcass traits. These results demonstrated that FOXO3 is a candidate gene influencing chicken growth. Our observations provide new clues to understand the molecular basis of chicken growth. PMID- 26366567 TI - dsdA Does Not Affect Colonization of the Murine Urinary Tract by Escherichia coli CFT073. AB - The urinary tract environment provides many conditions that deter colonization by microorganisms. D-serine is thought to be one of these stressors and is present at high concentrations in urine. D-serine interferes with L-serine and pantothenate metabolism and is bacteriostatic to many species. Uropathogenic Escherichia coli commonly possess the dsdCXA genetic locus, which allows them to use D-serine as a sole carbon, nitrogen, and energy source. It was previously reported that in the model UPEC strain CFT073, a dsdA mutant outcompetes wild type in the murine model of urinary tract infection. This "hypercolonization" was used to propose a model whereby UPEC strains sense D-serine in the urinary tract and subsequently up-regulate genes necessary for pathogenesis. Here, we show that inactivation of dsdA does not lead to hypercolonization. We suggest that this previously observed effect is due to an unrecognized secondary mutation in rpoS and that some D-serine specific effects described in other studies may be affected by the rpoS status of the strains used. Inactivation of dsdA in the original clinical isolate of CFT073 gives CFT073 DeltadsdA a growth defect in human urine and renders it unable to grow on minimal medium containing D-serine as the sole carbon source. However, CFT073 DeltadsdA is able to colonize the urinary tracts of CBA/J mice indistinguishably from wild type. These findings indicate that D-serine catabolism, though it may play role(s) during urinary tract infection, does not affect the ability of uropathogenic E. coli to colonize the murine urinary tract. PMID- 26366568 TI - Localized Modeling of Biochemical and Flow Interactions during Cancer Cell Adhesion. AB - This work focuses on one component of a larger research effort to develop a simulation tool to model populations of flowing cells. Specifically, in this study a local model of the biochemical interactions between circulating melanoma tumor cells (TC) and substrate adherent polymorphonuclear neutrophils (PMN) is developed. This model provides realistic three-dimensional distributions of bond formation and attendant attraction and repulsion forces that are consistent with the time dependent Computational Fluid Dynamics (CFD) framework of the full system model which accounts local pressure, shear and repulsion forces. The resulting full dynamics model enables exploration of TC adhesion to adherent PMNs, which is a known participating mechanism in melanoma cell metastasis. The model defines the adhesion molecules present on the TC and PMN cell surfaces, and calculates their interactions as the melanoma cell flows past the PMN. Biochemical rates of reactions between individual molecules are determined based on their local properties. The melanoma cell in the model expresses ICAM-1 molecules on its surface, and the PMN expresses the beta-2 integrins LFA-1 and Mac-1. In this work the PMN is fixed to the substrate and is assumed fully rigid and of a prescribed shear-rate dependent shape obtained from micro-PIV experiments. The melanoma cell is transported with full six-degrees-of-freedom dynamics. Adhesion models, which represent the ability of molecules to bond and adhere the cells to each other, and repulsion models, which represent the various physical mechanisms of cellular repulsion, are incorporated with the CFD solver. All models are general enough to allow for future extensions, including arbitrary adhesion molecule types, and the ability to redefine the values of parameters to represent various cell types. The model presented in this study will be part of a clinical tool for development of personalized medical treatment programs. PMID- 26366569 TI - The Recovery of Plastid Function Is Required for Optimal Response to Low Temperatures in Arabidopsis. AB - Cold acclimation is an essential response in higher plants to survive freezing temperatures. Here, we report that two independent mutant alleles of the H subunit of Mg-chelatase, CHLH, gun5-1 and cch in Arabidopsis are sensitive to low temperatures. Plants were grown in photoperiodic conditions and exposed to low temperatures for short- and long-term periods. Tetrapyrrole biosynthesis was initially significantly inhibited in response to low temperature but recovered in wild type (Col-0), although the tetrapyrrole levels were lower in cold compared to control conditions. The gun5-1 and cch alleles showed an inability to recover chlorophyll biosynthesis in addition to a significant decrease in freezing tolerance. We found that the impaired plastid function in the CHLH mutant plants resulted in compromised de novo protein synthesis at low temperatures. The expression of the transcription factors CBF1-3 was super-induced in gun5-1 and cch mutant alleles but expression levels of their target genes, COR15a, COR47 and COR78 were similar or even lower compared to Col-0. In addition, the protein levels of COR15a were lower in gun5-1 and cch and a general defect in protein synthesis could be seen in the gun5-1 mutant following a 35S labelling experiment performed at low temperature. Taken together, our results demonstrate the importance of a functional chloroplast for the cold acclimation process and further suggest that impaired plastid function could result in inhibition of protein synthesis at low temperature. PMID- 26366570 TI - Experimental Infection of Ornithodoros erraticus sensu stricto with Two Portuguese African Swine Fever Virus Strains. Study of Factors Involved in the Dynamics of Infection in Ticks. AB - African swine fever (ASF) is a frequently devastating hemorrhagic disease of domestic pigs and wild boar and Ornithodoros erraticus sensu stricto argasid ticks are the only biological vectors of African swine fever virus (ASFV) known to occur in Europe. Recently this disease emerged in Eastern Europe and Russian Federation, showing a huge potential for a rapid spread between countries. There is some risk of re-emergence of ASF in the countries where these ticks exist, that can contribute for the persistence of infection and compromise control measures. In this study we aimed to identify factors that determine the probability of infection and its dynamics in the tick vector Ornithodoros erraticus sensu stricto, with two Portuguese strains of ASFV. Our results suggest that these ticks have a high likelihood of excreting the two haemadsorbing ASF viruses of different host origins and that, in field surveys, the analysis of adults and 5th nymphal stage can provide the best chance of detecting virus infection. The results also indicate that infection of pigs with highly virulent ASF viruses will promote higher rates of infection and a higher likelihood for virus excretion by ticks. Nevertheless, there is also a risk, although lower, that ticks can become infected on pigs that have overcome the acute phase of infection, which was simulated in our study by membrane feeding ticks with low titres of virus. We believe these results can be valuable in designing and interpreting the results of ASF control programmes, and future work can also be undertaken as our dataset is released under open access, to perform studies in risk assessment for ASFV persistence in a region where O. erraticus sensu stricto ticks are present. PMID- 26366572 TI - Correction: Gene Transfer to Chicks Using Lentiviral Vectors Administered via the Embryonic Chorioallantoic Membrane. PMID- 26366571 TI - Biomarkers of Host Response Predict Primary End-Point Radiological Pneumonia in Tanzanian Children with Clinical Pneumonia: A Prospective Cohort Study. AB - BACKGROUND: Diagnosing pediatric pneumonia is challenging in low-resource settings. The World Health Organization (WHO) has defined primary end-point radiological pneumonia for use in epidemiological and vaccine studies. However, radiography requires expertise and is often inaccessible. We hypothesized that plasma biomarkers of inflammation and endothelial activation may be useful surrogates for end-point pneumonia, and may provide insight into its biological significance. METHODS: We studied children with WHO-defined clinical pneumonia (n = 155) within a prospective cohort of 1,005 consecutive febrile children presenting to Tanzanian outpatient clinics. Based on x-ray findings, participants were categorized as primary end-point pneumonia (n = 30), other infiltrates (n = 31), or normal chest x-ray (n = 94). Plasma levels of 7 host response biomarkers at presentation were measured by ELISA. Associations between biomarker levels and radiological findings were assessed by Kruskal-Wallis test and multivariable logistic regression. Biomarker ability to predict radiological findings was evaluated using receiver operating characteristic curve analysis and Classification and Regression Tree analysis. RESULTS: Compared to children with normal x-ray, children with end-point pneumonia had significantly higher C reactive protein, procalcitonin and Chitinase 3-like-1, while those with other infiltrates had elevated procalcitonin and von Willebrand Factor and decreased soluble Tie-2 and endoglin. Clinical variables were not predictive of radiological findings. Classification and Regression Tree analysis generated multi-marker models with improved performance over single markers for discriminating between groups. A model based on C-reactive protein and Chitinase 3-like-1 discriminated between end-point pneumonia and non-end-point pneumonia with 93.3% sensitivity (95% confidence interval 76.5-98.8), 80.8% specificity (72.6-87.1), positive likelihood ratio 4.9 (3.4-7.1), negative likelihood ratio 0.083 (0.022-0.32), and misclassification rate 0.20 (standard error 0.038). CONCLUSIONS: In Tanzanian children with WHO-defined clinical pneumonia, combinations of host biomarkers distinguished between end-point pneumonia, other infiltrates, and normal chest x-ray, whereas clinical variables did not. These findings generate pathophysiological hypotheses and may have potential research and clinical utility. PMID- 26366573 TI - Membrane Curvature Sensing by Amphipathic Helices Is Modulated by the Surrounding Protein Backbone. AB - Membrane curvature is involved in numerous biological pathways like vesicle trafficking, endocytosis or nuclear pore complex assembly. In addition to its topological role, membrane curvature is sensed by specific proteins, enabling the coordination of biological processes in space and time. Amongst membrane curvature sensors are the ALPS (Amphipathic Lipid Packing Sensors). ALPS motifs are short peptides with peculiar amphipathic properties. They are found in proteins targeted to distinct curved membranes, mostly in the early secretory pathway. For instance, the ALPS motif of the golgin GMAP210 binds trafficking vesicles, while the ALPS motif of Nup133 targets nuclear pores. It is not clear if, besides curvature sensitivity, ALPS motifs also provide target specificity, or if other domains in the surrounding protein backbone are involved. To elucidate this aspect, we studied the subcellular localization of ALPS motifs outside their natural protein context. The ALPS motifs of GMAP210 or Nup133 were grafted on artificial fluorescent probes. Importantly, ALPS motifs are held in different positions and these contrasting architectures were mimicked by the fluorescent probes. The resulting chimeras recapitulated the original proteins localization, indicating that ALPS motifs are sufficient to specifically localize proteins. Modulating the electrostatic or hydrophobic content of Nup133 ALPS motif modified its avidity for cellular membranes but did not change its organelle targeting properties. In contrast, the structure of the backbone surrounding the helix strongly influenced targeting. In particular, introducing an artificial coiled-coil between ALPS and the fluorescent protein increased membrane curvature sensitivity. This coiled-coil domain also provided membrane curvature sensitivity to the amphipathic helix of Sar1. The degree of curvature sensitivity within the coiled-coil context remains correlated to the natural curvature sensitivity of the helices. This suggests that the chemistry of ALPS motifs is a key parameter for membrane curvature sensitivity, which can be further modulated by the surrounding protein backbone. PMID- 26366574 TI - Using MDEFT MRI Sequences to Target the GPi in DBS Surgery. AB - OBJECTIVE: Recent advances in different MRI sequences have enabled direct visualization and targeting of the Globus pallidus internus (GPi) for DBS surgery. Modified Driven Equilibrium Fourier Transform (MDEFT) MRI sequences provide high spatial resolution and an excellent contrast of the basal ganglia with low distortion. In this study, we investigate if MDEFT sequences yield accurate and reliable targeting of the GPi and compare direct targeting based on MDEFT sequences with atlas-based targeting. METHODS: 13 consecutive patients considered for bilateral GPi-DBS for dystonia or PD were included in this study. Preoperative targeting of the GPi was performed visually based on MDEFT sequences as well as by using standard atlas coordinates. Postoperative CT imaging was performed to calculate the location of the implanted leads as well as the active electrode(s). The coordinates of both visual and atlas based targets were compared. The stereotactic coordinates of the lead and active electrode(s) were calculated and projected on the segmented GPi. RESULTS: On MDEFT sequences the GPi was well demarcated in most patients. Compared to atlas-based planning the mean target coordinates were located significantly more posterior. Subgroup analysis showed a significant difference in the lateral coordinate between dystonia (LAT = 19.33 +/- 0.90) and PD patients (LAT = 20.67 +/- 1.69). Projected on the segmented preoperative GPi the active contacts of the DBS electrode in both dystonia and PD patients were located in the inferior and posterior part of the structure corresponding to the motor part of the GPi. CONCLUSIONS: MDEFT MRI sequences provide high spatial resolution and an excellent contrast enabling precise identification and direct visual targeting of the GPi. Compared to atlas based targeting, it resulted in a significantly different mean location of our target. Furthermore, we observed a significant variability of the target among the PD and dystonia subpopulation suggesting accurate targeting for each individual patient. PMID- 26366575 TI - Implicit Attitudes towards People with Intellectual Disabilities: Their Relationship with Explicit Attitudes, Social Distance, Emotions and Contact. AB - Implicit attitude research has expanded rapidly over the last decade and is seen as very promising as it counters biases present in much attitude research such as social desirability. However, most research in the area of intellectual disabilities has focused on explicit attitudes alone. This study examined implicit attitudes to this population and also examined their association with emotional reactions and contact, which have previously been found to have a significant influence on attitudes and stigma. A web based survey consisting of a single target Implicit Association Test, measures of explicit attitudes, social distance, and emotional reactions towards and contact with individuals with intellectual disabilities was completed by 326 adult UK residents. Implicit attitudes were not significantly associated with explicit attitudes, social distance or emotional reactions. Instead there were small to moderate associations between emotional reactions and explicit attitudes and social distance. Implicit attitudes did not vary according to participants' level of contact with individuals with intellectual disabilities, type of the contact relationship (voluntary versus involuntary), gender or educational attainment. In contrast, these participant characteristics did affect explicit attitudes and social distance. Implicit attitudes towards individuals with intellectual disabilities were somewhat negative and, unlike explicit attitudes and stigma, did not vary according to participant demographics or contact. As they may have a negative impact on the lives of people with intellectual disabilities, implicit attitudes merit increased attention in research and interventions in the intellectual disabilities field. PMID- 26366576 TI - Degradation of Root Community Traits as Indicator for Transformation of Tropical Lowland Rain Forests into Oil Palm and Rubber Plantations. AB - Conversion of tropical forests into intensely managed plantations is a threat to ecosystem functions. On Sumatra, Indonesia, oil palm (Elaeis guineensis) plantations are rapidly expanding, displacing rain forests and extensively used rubber (Hevea brasiliensis) agro-forests. Here, we tested the influence of land use systems on root traits including chemical traits (carbon, nitrogen, mineral nutrients, potentially toxic elements [aluminium, iron] and performance traits (root mass, vitality, mycorrhizal colonization). Traits were measured as root community-weighed traits (RCWTs) in lowland rain forests, in rubber agro-forests mixed with rain forest trees, in rubber and oil palm plantations in two landscapes (Bukit Duabelas and Harapan, Sumatra). We hypothesized that RCWTs vary with land use system indicating increasing transformation intensity and loss of ecosystem functions. The main factors found to be related to increasing transformation intensity were declining root vitality and root sulfur, nitrogen, carbon, manganese concentrations and increasing root aluminium and iron concentrations as well as increasing spore densities of arbuscular mycorrhizas. Mycorrhizal abundance was high for arbuscular and low for ectomycorrhizas and unrelated to changes in RCWTs. The decline in RCWTs showed significant correlations with soil nitrogen, soil pH and litter carbon. Thus, our study uncovered a relationship between deteriorating root community traits and loss of ecosystem functionality and showed that increasing transformation intensity resulted in decreasing root nutrition and health. Based on these results we suggest that land management that improves root vitality may enhance the ecological functions of intense tropical production systems. PMID- 26366577 TI - Targeting the Microbiome in Inflammatory Bowel Disease: Critical Evaluation of Current Concepts and Moving to New Horizons. AB - Microorganisms present in the intestine possess proinflammatory or anti inflammatory activities which may modulate inflammatory bowel disease (IBD). The concepts followed by researchers in trying to target the microbiota in IBD were to decrease pathogens or pathobionts, or only the microbial load, and more recently, to favor growth and persistence of favorable microorganisms. We review, here, those concepts and critically analyze the clinical data (especially randomized controlled trials) obtained using antibiotics and probiotics. We eventually present and criticize the rational and data obtained so far following new research strategies including the use of new probiotics, genetically modified organisms and fecal transplantation. PMID- 26366579 TI - Correction: Twenty Years of Medically-Attended Pediatric Varicella and Herpes Zoster in Ontario, Canada: A Population-Based Study. PMID- 26366578 TI - Antisense Morpholino Oligonucleotides Reduce Neurofilament Synthesis and Inhibit Axon Regeneration in Lamprey Reticulospinal Neurons. AB - The sea lamprey has been used as a model for the study of axonal regeneration after spinal cord injury. Previous studies have suggested that, unlike developing axons in mammal, the tips of regenerating axons in lamprey spinal cord are simple in shape, packed with neurofilaments (NFs), and contain very little F-actin. Thus it has been proposed that regeneration of axons in the central nervous system of mature vertebrates is not based on the canonical actin-dependent pulling mechanism of growth cones, but involves an internal protrusive force, perhaps generated by the transport or assembly of NFs in the distal axon. In order to assess this hypothesis, expression of NFs was manipulated by antisense morpholino oligonucleotides (MO). A standard, company-supplied MO was used as control. Axon retraction and regeneration were assessed at 2, 4 and 9 weeks after MOs were applied to a spinal cord transection (TX) site. Antisense MO inhibited NF180 expression compared to control MO. The effect of inhibiting NF expression on axon retraction and regeneration was studied by measuring the distance of axon tips from the TX site at 2 and 4 weeks post-TX, and counting the number of reticulospinal neurons (RNs) retrogradely labeled by fluorescently-tagged dextran injected caudal to the injury at 9 weeks post-TX. There was no statistically significant effect of MO on axon retraction at 2 weeks post-TX. However, at both 4 and 9 weeks post-TX, inhibition of NF expression inhibited axon regeneration. PMID- 26366581 TI - Reliability and Validity of the Korean Version of the Perceived Stress Scale-10 (K-PSS-10) in Older Adults. AB - The purpose of the current study was to examine the reliability and validity of the Korean version of the Perceived Stress Scale-10 (K-PSS-10). After translation and back-translation of the original PSS-10, a convenience sample of 342 community-dwelling older adults was recruited from senior community centers. Data were analyzed using factor analysis, Pearson's correlation coefficient, and Cronbach's alpha. Using factor analysis with principal axis factoring with oblimin rotation, two factors were extracted. The two-factor solution explained 49.71% of the total variance. Internal consistency values for negative and positive subdomains were 0.87 and 0.71, respectively. Moderate relationships were found between a negative response to stress and depression (r = 0.42, p < 0.001) and quality of life (r = -0.45, p < 0.001). A positive response to stress had moderate significant correlations with depression (r = 0.30, p < 0.001) and quality of life (r = -0.36, p < 0.001). Overall, the K-PSS-10 had good reliability, with a Cronbach's alpha of 0.75. The K-PSS-10 demonstrated the desired psychometric properties and was easy to use to assess the stress of community-dwelling older adults in Korea. PMID- 26366580 TI - Differential Gene Expression and Infection Profiles of Cutaneous and Mucosal Leishmania braziliensis Isolates from the Same Patient. AB - BACKGROUND: Leishmaniasis is a complex disease in which clinical outcome depends on factors such as parasite species, host genetics and immunity and vector species. In Brazil, Leishmania (Viannia) braziliensis is a major etiological agent of cutaneous (CL) and mucosal leishmaniasis (MCL), a disfiguring form of the disease, which occurs in ~10% of L. braziliensis-infected patients. Thus, clinical isolates from patients with CL and MCL may be a relevant source of information to uncover parasite factors contributing to pathogenesis. In this study, we investigated two pairs of L. (V.) braziliensis isolates from mucosal (LbrM) and cutaneous (LbrC) sites of the same patient to identify factors distinguishing parasites that migrate from those that remain at the primary site of infection. METHODOLOGY/PRINCIPAL FINDINGS: We observed no major genomic divergences among the clinical isolates by molecular karyotype and genomic sequencing. RT-PCR revealed that the isolates lacked Leishmania RNA virus (LRV). However, the isolates exhibited distinct in vivo pathogenesis in BALB/c mice; the LbrC isolates were more virulent than the LbrM isolates. Metabolomic analysis revealed significantly increased levels of 14 metabolites in LbrC parasites and 31 metabolites in LbrM parasites that were mainly related to inflammation and chemotaxis. A proteome comparative analysis revealed the overexpression of LbrPGF2S (prostaglandin f2-alpha synthase) and HSP70 in both LbrC isolates. Overexpression of LbrPGF2S in LbrC and LbrM promastigotes led to an increase in infected macrophages and the number of amastigotes per cell at 24-48 h post infection (p.i.). CONCLUSIONS/SIGNIFICANCE: Despite sharing high similarity at the genome structure and ploidy levels, the parasites exhibited divergent expressed genomes. The proteome and metabolome results indicated differential profiles between the cutaneous and mucosal isolates, primarily related to inflammation and chemotaxis. BALB/c infection revealed that the cutaneous isolates were more virulent than the mucosal parasites. Furthermore, our data suggest that the LbrPGF2S protein is a candidate to contribute to parasite virulence profiles in the mammalian host. PMID- 26366582 TI - Falls Self-Efficacy in German Nursing Home Residents: Assessment of Validity and Determination of a Cutoff Point. AB - Approximately one in every two German nursing home residents falls at least once in a 1-year period and just as many report a fear of falling. It has been hypothesized that falls self-efficacy mediates the relationship between fear of falling and functional ability. The aim of the current study was to develop the German Nursing Home Falls Self-Efficacy Scale, examine its validity, and estimate a cutoff point to differentiate nursing home residents with low or high falls self-efficacy. Nursing home residents were assessed at baseline (n = 178, mean age = 83.7 years) and 6-month follow up (n = 115, mean age = 83.9 years). Factorial and construct validity analyses provided preliminary support for the validity of the scale. A cutoff point of 11.5 was generated by receiver operating characteristic curve analysis. This scale may assist health care professionals in differentiating between nursing home residents with low and high falls self efficacy and supporting residents in providing appropriate interventions. [Res Gerontol Nurs. 2016; 9(3):134-144.]. PMID- 26366583 TI - [Progressive Bilateral Chorioretinitis]. PMID- 26366584 TI - [Therapy of Presumed Ocular Histoplasmosis Syndrome (POHS) with Bevacizumab]. PMID- 26366585 TI - ["New from Old": Hermann Cohn and the Concept of Light in the Prevention of Myopia 1867-2015]. PMID- 26366586 TI - Quick discrimination of heavy metal resistant bacterial populations using infrared spectroscopy coupled with chemometrics. AB - Lead and cadmium are frequently encountered heavy metals in industrially polluted areas. Many heavy metal resistant bacterial strains have a high biosorption capacity and thus are good candidates for the removal of toxic metals from the environment. However, as of yet there is no accurate method for discrimination of highly adaptive bacterial strains among the populations present in a given habitat. In this study, we aimed to find distinguishing molecular features of lead and cadmium resistant bacteria using Attenuated Total Reflectance-Fourier Transformed Infrared (ATR-FT-IR) spectroscopy and chemometric approaches. Our results demonstrated that both control and metal exposed E. coli and S. aureus strains could be successfully discriminated from each other using hierarchical cluster and principal component analysis methods. Moreover, we found that lead exposed bacterial strains could be successfully discriminated from cadmium exposed ones with a high heterogeneity value. These clear discriminations can be described by the ability of a bacterium to change its metabolism in terms of the content and structure of cellular macromolecules under heavy metal stress. In our case, cadmium and lead-induced genetic response systems in bacteria caused remarkable alterations in overall cellular metabolism. Bacteria deal with a heavy metal stress by altering nucleic acid methylations and lipid and protein synthesis. Heavy metal burden led to the development of relevant metabolic changes in proteins, lipids, and nucleic acids of the resistant bacteria described in this study. Our approach showed that infrared spectra obtained via ATR-FT-IR spectroscopy coupled with chemometric analysis can be utilized for rapid, low-cost, informative, reliable, and operator-independent discrimination of resistant bacterial populations. PMID- 26366587 TI - Relativistic kinematics formulation of the polarization effects of Jones-Mueller matrices. AB - The polarization of a partially coherent, transverse electric, electromagnetic plane wave is commonly represented by a Stokes vector. The similarity between Stokes vectors and four-momentum vectors in special relativity (SR) is studied in depth. The set of Stokes vectors naturally possesses a Euclidean and a Lorentzian geometry. The latter is used to express the polarization-altering properties of Jones-Mueller matrices in a simple and elegant way. In particular, it is shown that the action of a diattenuator on a Stokes vector can be understood in terms of the addition law for velocities from SR. An important simplification in the resulting mathematical expressions further arises if the degree of polarization of a Stokes vector is represented by a hyperbolic polarization angle. This then allows us to demonstrate that the output hyperbolic polarization angle is related to a diattenuator hyperbolic polarization angle and the input hyperbolic polarization angle by the hyperbolic law of cosines holding in a hyperbolic triangle. PMID- 26366588 TI - Action recognition through discovering distinctive action parts. AB - Recent methods based on midlevel visual concepts have shown promising capabilities in the human action recognition field. Automatically discovering semantic entities such as action parts remains challenging. In this paper, we present a method of automatically discovering distinctive midlevel action parts from video for recognition of human actions. We address this problem by learning and selecting a collection of discriminative and representative action part detectors directly from video data. We initially train a large collection of candidate exemplar-linear discriminant analysis detectors from clusters obtained by clustering spatiotemporal patches in whitened space. To select the most effective detectors from the vast array of candidates, we propose novel coverage entropy curves (CE curves) to evaluate a detector's capability of distinguishing actions. The CE curves characterize the correlation between the representative and discriminative power of detectors. In the experiments, we apply the mined part detectors as a visual vocabulary to the task of action recognition on four datasets: KTH, Olympic Sports, UCF50, and HMDB51. The experimental results demonstrate the effectiveness of the proposed method and show the state-of-the art recognition performance. PMID- 26366589 TI - Preparing the generalized Harvey-Shack rough surface scattering method for use with the discrete ordinates method. AB - The paper shows how to implement the generalized Harvey-Shack (GHS) method for isotropic rough surfaces discretized in a polar coordinate system and approximated using Fourier series. This is particularly relevant for the use of the GHS method as a boundary condition for radiative transfer problems in slab geometries, where the discrete ordinates method can be applied to solve the problem. Furthermore, such an implementation is a more convenient discretization of the problem than the traditional direction cosine space that has its strengths in analytical problems and intuitive understanding (mainly due to its translation invariance). A computer implementation of scattering from a Gaussian rough surface with Gaussian autocovariance written in Python is included at the end of the paper. PMID- 26366590 TI - Analysis of optical vortices with suppressed sidelobes using modified Bessel-like function and trapezoid annulus modulation structures. AB - Two amplitude modulation methods, including modified Bessel-like function modulation structure and trapezoid annulus structure, for suppressing sidelobes of optical vortices are studied. In the former approach, we propose that the order of the Bessel-like function can be an additional parameter to modulate diffraction patterns of optical vortices motivated by the idea of conventional annulus structures. Furthermore, new Bessel-like modulation functions are introduced to solve the problem of low diffraction efficiency of the original one. Trapezoid annulus structure is proposed as a compromise structure between the modified Bessel-like modulation structure and the conventional annulus one, and has advantages of both. It is demonstrated that these two approaches can achieve high-quality optical vortices with suppressed sidelobes effectively, and the relative structures behave as more flexible and applicable structures for producing optical vortices with large coverage of topological charges, which suggests great potential in simplifying the structure designing procedure. These reliable and generalized structures for generating high-quality optical vortices will help to promote the development of future optical communication and optical manipulation significantly. PMID- 26366591 TI - Tailoring the negative-refractive-index metamaterials composed of semiconductor metal-semiconductor gold ring/disk cavity heptamers to support strong Fano resonances in the visible spectrum. AB - In this study, we investigated numerically the plasmon response of a planar negative-index metamaterial composed of symmetric molecular orientations of Au ring/disk nanocavities in a heptamer cluster. Using the plasmon hybridization theory and considering the optical response of an individual nanocluster, we determined the accurate geometrical sizes for a ring/disk nanocavity heptamer. It is shown that the proposed well-organized nanocluster can be tailored to support strong and sharp Fano resonances in the visible spectrum. Surrounding and filling the heptamer clusters by various metasurfaces with different chemical characteristics, and illuminating the structure with an incident light source, we proved that this configuration reflects low losses and isotropic features, including a pronounced Fano dip in the visible spectrum. Technically, employing numerical methods and tuning the geometrical sizes of the structure, we tuned and induced the Fano dip in the visible range, while the dark and bright plasmon resonance extremes are blueshifted to shorter wavelengths dramatically. Considering the calculated transmission window, we quantified the effective refractive index for the structure, while the substance of the substrate material was varied. Using Si, GaP, and InP semiconductors as substrate materials, we calculated and compared the corresponding figure of merit (FOM) for different regimes. The highest possible FOM was obtained for the GaP-Au-GaP negative refractive-index metamaterial composed of ring/disk nanocavity heptamers as 62.4 at lambda~690 nm (arounnd the position of the Fano dip). Despite the outstanding symmetric nature of the suggested heptamer array, we provided sharp Fano dips by the appropriate tuning of the geometrical and chemical parameters. This study yields a method to employ ring/disk nanocavity heptamers as a negative-refractive index metamaterial in designing highly accurate localization of surface plasmon resonance sensing devices and biochemical sensors. PMID- 26366592 TI - Effect of rotational diffusion in an orientational potential well on the point spread function of electric dipole emitters. AB - A study is presented of the point spread function (PSF) of electric dipole emitters that go through a series of absorption-emission cycles while the dipole orientation is changing due to rotational diffusion within the constraint of an orientational potential well. An analytical expression for the PSF is derived valid for arbitrary orientational potential wells in the limit of image acquisition times much larger than the rotational relaxation time. This framework is used to study the effects of the direction of incidence, polarization, and degree of coherence of the illumination. In the limit of fast rotational diffusion on the scale of the fluorescence lifetime the illumination influences only the PSF height, not its shape. In the limit of slow rotational diffusion on the scale of the fluorescence lifetime there is a significant effect on the PSF shape as well, provided the illumination is (partially) coherent. For oblique incidence, illumination asymmetries can arise in the PSF that give rise to position offsets in localization based on Gaussian spot fitting. These asymmetries persist in the limit of free diffusion in a zero orientational potential well. PMID- 26366593 TI - Diffraction model of peristrophic multiplexing with spherical reference wave. AB - Multiplexing recording is a primary contributor to determining the recording density in holographic data storage. Therefore, many different kinds of recording methods have been proposed. Among them, the method that utilizes spherical waves as reference waves is characterized by the ability to enable multiplexing recording only by moving (shifting or rotating) the recording medium. In our research, we propose a theoretical diffraction model of peristrophic multiplexing with a spherical reference wave and evaluate the diffraction efficiency; this multiplexing recording method has incorporated spherical reference waves in rotation of the media. Additionally, we verify the effectiveness of the model by comparing it with experimental results. PMID- 26366594 TI - General expressions for the refractive indices of absorbing biaxial media as a function of the angle of incidence. AB - In this work we obtain general expressions for the complex refractive indices of refracted waves as a function of the angle of incidence in the case of an electromagnetic wave propagating in a transparent isotropic medium that reaches an interface with a biaxial absorbing medium. The biaxial absorbing medium is only required to have a diagonalizable complex dielectric tensor. Obtained expressions can be applied to any orientation of the principal axes and can be specialized for isotropic, uniaxial or biaxial, or transparent or absorbing media. By using these expressions we have also obtained the surface of indices and the surface of absorption coefficients for an example of a biaxial absorbing medium. PMID- 26366595 TI - Portable monocular light pen vision measurement system. AB - This paper introduces a portable monocular vision measurement system that is suitable for measuring complex object surfaces or hidden features. The system mainly consists of a light pen, a camera, and a portable computer. First, without any control point, a camera calibration method based on the bundle adjustment is developed. This method can also be applied to calculate the positions of the feature points on the light pen. Second, we calibrate the probe tip center, since the position of the replaceable stylus is uncertain. Last, by taking images of the light pen when the stylus contacts the object's surface, we get the measured point's position. This measuring system is portable, efficient, and high precision. Experiments show that in a 100 mm*200 mm field, the position errors of 66 points are less than 30 MUm. PMID- 26366596 TI - Intelligent speckle reducing anisotropic diffusion algorithm for automated 3-D ultrasound images. AB - A novel 3-D filtering method is presented for speckle reduction and detail preservation in automated 3-D ultrasound images. First, texture features of an image are analyzed by using the improved quadtree (QT) decomposition. Then, the optimal homogeneous and the obvious heterogeneous regions are selected from QT decomposition results. Finally, diffusion parameters and diffusion process are automatically decided based on the properties of these two selected regions. The computing time needed for 2-D speckle reduction is very short. However, the computing time required for 3-D speckle reduction is often hundreds of times longer than 2-D speckle reduction. This may limit its potential application in practice. Because this new filter can adaptively adjust the time step of iteration, the computation time is reduced effectively. Both synthetic and real 3 D ultrasound images are used to evaluate the proposed filter. It is shown that this filter is superior to other methods in both practicality and efficiency. PMID- 26366597 TI - Generalized propagation of light through optical systems. I. Mathematical basics. AB - The propagation of an input field through tilted and curved surfaces is presented and applied for a field tracing routine. This routine employs a ray tracing method for optimal coordinate customization, which is done due to the strong linear phase terms that arise because of tilted coordinates on one hand and the possibility of an application of fast numerical routines on the other. Several methods are proposed on how to optimize the field sampling during the propagation process, as for the astigmatic phase front problem and the curvature of the surface itself. Two solution methods are given to propagate from the curved surface through the homogeneous space to another two-dimensional submanifold. The approach is fully vectorial, Maxwell exact excluding only surface curvature terms for the Fresnel coefficients. A simple numerical propagation example is given. PMID- 26366598 TI - Condition for generating the same scattered spectral density by random and deterministic media. AB - We present a condition for generating the same scattered spectral density by random and deterministic media. Examples of light waves on scattering from a Gaussian-centered deterministic medium and a Gaussian-correlated quasi homogeneous random medium are discussed. It is shown that the normalized far-zone scattered spectral density produced by a Gaussian-centered deterministic medium and by a Gaussian-correlated quasi-homogeneous random medium will be identical provided that the square of the effective width of normalized correlation coefficient of the quasi-homogeneous random medium is twice the square of the effective width of scattering potential of the determinate medium. PMID- 26366599 TI - Monte Carlo simulation of retinal light absorption by infants. AB - Retinal damage can occur in normal ambient lighting conditions. Infants are particularly vulnerable to retinal damage, and thousands of preterm infants sustain vision damage each year. The size of the ocular fundus affects retinal light absorption, but there is a lack of understanding of this effect for infants. In this work, retinal light absorption is simulated for different ocular fundus sizes, wavelengths, and pigment concentrations by using the Monte Carlo method. The results indicate that the neural retina light absorption per volume for infants can be two or more times that for adults. PMID- 26366600 TI - Electromagnetic scattering by two concentric spheres buried in a stratified material. AB - In this paper, a rigorous method to analyze the electromagnetic scattering of an elliptically polarized plane wave by two concentric spheres buried in a dielectric stratified medium is presented. The interaction of the electromagnetic radiation with the stratified material is taken into account by means of the transfer matrix approach, in this way we can consider the stratified medium as an effective single interface. All the electromagnetic fields are expanded in series of spherical vector harmonics. The transmitted field through the stratified medium is obtained by means of the effective transmission coefficient. This field is scattered by the two concentric spheres, and the scattered field interacts again with the stratified material. The scattered-reflected and scattered transmitted fields by the layered medium are computed by exploiting the plane wave spectrum of the scattered field, considering the reflection and transmission of each elementary plane wave by the effective interface. The boundary conditions imposition on the spheres' surfaces leads to a linear system that returns the unknown coefficients of the problem. A numerical code has been implemented to compute the field over all the space. In order to compute the scattered fields, a truncation criterion has been proposed for the numerical evaluation of the series. Finally, to validate the presented method, comparisons between the results of the proposed code and the results of simulations with a software based on the finite element method have been implemented, showing very good agreement. PMID- 26366601 TI - Superresolution with full-polarized tomographic diffractive microscopy. AB - Tomographic diffractive microscopy is a three-dimensional imaging technique that reconstructs the permittivity map of the probed sample from its scattered field, measured both in phase and in amplitude. Here, we detail how polarization resolved measurements permit us to significantly improve the accuracy and the resolution of the reconstructions, compared to the conventional scalar treatments used so far. An isotropic transverse resolution of about 100 nm at a wavelength of 475 nm is demonstrated using this approach. PMID- 26366602 TI - Concentric circular trajectory sampling for super-resolution and image mosaicing. AB - Ubiquitous applications in diverse fields motivate large-area sampling, super resolution (SR) and image mosaicing. However, conventional translational sampling has drawbacks including laterally constrained variations between samples. Meanwhile, existing rotational sampling methods do not consider the uniformity of sampling points in Cartesian coordinates, resulting in additional distortion errors in sampled images. We design a novel optimized concentric circular trajectory sampling (OCCTS) method to acquire image information uniformly at fast sampling speeds. The sampling method allows multiple low-resolution images for conventional SR algorithms to be acquired by adding small variations in the angular dimension. Experimental results demonstrate that OCCTS can beat comparable CCTS methods that lack optimized sampling densities by reducing sampling time by more than 11.5% while maintaining 50% distortion error reduction. The SR quality of OCCTS has at least 5.2% fewer distortion errors than the comparable CCTS methods. This paper is the first, to the best of our knowledge, to present an OCCTS method for SR and image mosaicing. PMID- 26366603 TI - Frequency correlations in reflection from random media. AB - We present a theoretical study of frequency correlations of light backscattered from a random scattering medium. This statistical quantity provides insight into the dynamics of multiple scattering processes accessible in theoretical and experimental investigations. For frequency correlations between field amplitudes, we derive a simple expression in terms of the path length distribution of the underlying backscattering processes. In a second step, we apply this relation to describe frequency correlations between intensities in the regime of weak disorder. Since, with increasing disorder strength, an unexplained breakdown of the angular structure of the frequency correlation function has recently been reported in experimental studies, we explore extensions of our model to the regime of stronger disorder. In particular, we show that closed scattering trajectories tend to suppress the angular dependence of the frequency correlation function. PMID- 26366604 TI - The color cone. AB - While the notion of a color cone can be found in writings of Maxwell, Helmholtz, Grassmann, and other scientists of the nineteenth century, it has not been clearly defined as yet. In this paper, the color cone is understood as the set of points in the cone excitation space produced by all possible lights. The spectral curve representing all the monochromatic lights is shown not to entirely belong to the color cone boundary, since its ends turn into the color cone interior. The monochromatic lights represented by the fragment of the spectral curve lying on the color cone boundary make up what is called the effective visible spectrum. The color cone is shown to be a convex hull of the conical surface through the fragment of the spectral curve representing the effective visible spectrum. The effective visible spectrum ends are shown to be determined by the photopigment spectral absorbance being independent of the prereceptor filters (e.g., the spectral transmittance of the lense and macular pigment). PMID- 26366605 TI - High quality computational ghost imaging using multi-fluorescent screen. AB - An alternative scheme for improvement of computational ghost imaging (GI) features is proposed based on a three-color fluorescent screen. While a monochrome fluorescent screen does not enhance the quality of ghost images in comparison with the ordinary GI technique, employment of a multi-fluorescent screen can be very effective. It is shown that the visibility, signal to noise ratio (SNR), and contrast to noise ratio (CNR) of the resultant ghost images are improved when a multi-fluorescent screen is used. In particular, the results prove 65%, 36%, and 95% improvement for visibility, SNR, and CNR over 2000 shots, respectively. Also shown is the possibility of reconstructing ghost images over a reduced number of shots (as small as 25) by increasing the number of colors on the screen, whereas ordinary GI is not possible with such a small number of shots. The results from simulations are checked with conducted experiments, and a good agreement between them is observed. PMID- 26366606 TI - Effective and efficient subjective testing of texture similarity metrics. AB - The development and testing of objective texture similarity metrics that agree with human judgments of texture similarity require, in general, extensive subjective tests. The effectiveness and efficiency of such tests depend on a careful analysis of the abilities of human perception and the application requirements. The focus of this paper is on defining performance requirements and testing procedures for objective texture similarity metrics. We identify three operating domains for evaluating the performance of a similarity metric: the ability to retrieve "identical" textures; the top of the similarity scale, where a monotonic relationship between metric values and subjective scores is desired; and the ability to distinguish between perceptually similar and dissimilar textures. Each domain has different performance goals and requires different testing procedures. For the third domain, we propose ViSiProG, a new Visual Similarity by Progressive Grouping procedure for conducting subjective experiments that organizes a texture database into clusters of visually similar images. The grouping is based on visual blending and greatly simplifies labeling image pairs as similar or dissimilar. ViSiProG collects subjective data in an efficient and effective manner, so that a relatively large database of textures can be accommodated. Experimental results and comparisons with structural texture similarity metrics demonstrate both the effectiveness of the proposed subjective testing procedure and the performance of the metrics. PMID- 26366607 TI - Differential Mueller matrix of a depolarizing homogeneous medium and its relation to the Mueller matrix logarithm. AB - The different z-dependence and non-commutativity of the two components of the differential Mueller matrix of a homogeneous depolarizing medium prevent its formal identification with the Mueller matrix logarithm. By using a classic linear differential equation expansion, we advance a procedure for the extraction of the elementary polarization properties, in terms of mean values and variances covariances, from the Mueller matrix logarithm. The approximate solution, based on the immediate identification of the differential matrix with the matrix logarithm, turns out to remain satisfactory up to relatively high depolarization levels. Physically interpreted experimental examples from the literature illustrate the formal developments. PMID- 26366608 TI - Decarboxylative 1,4-Addition of alpha-Oxocarboxylic Acids with Michael Acceptors Enabled by Photoredox Catalysis. AB - Enabled by iridium photoredox catalysis, 2-oxo-2-(hetero)arylacetic acids were decarboxylatively added to various Michael acceptors including alpha,beta unsaturated ester, ketone, amide, aldehyde, nitrile, and sulfone at room temperature. The reaction presents a new type of acyl Michael addition using stable and easily accessible carboxylic acid to formally generate acyl anion through photoredox-catalyzed radical decarboxylation. PMID- 26366609 TI - Two-Component Domino Reactions Initiated from Ketenes: Serendipitous Synthesis of Quinolizidinones Analogous to Chelated Lobeline's Conformation. AB - An original and efficient synthesis of quinolizidinones through a one-pot two component cascade reaction of norlobelanine with in situ generated ketenes is reported. Functionalized fused azabicyclic scaffolds bearing multiple stereogenic centers were prepared with excellent diastereoselectivities. Mild optimized conditions involving a key "shuttle base" deprotonation strategy was applied to the synthesis, in a short sequence, of a constrained mimetic of the privileged H bonded conformation of (-)-lobeline. PMID- 26366610 TI - 2H-[1,2,3]Triazolo[4,5-c]pyridine Cored Organic Dyes Achieving a High Efficiency: a Systematic Study of the Effect of Different Donors and pi Spacers. AB - New D-A-pi-A-based isomeric sensitizers, PTNn (n = 1-2) and NPTn (n = 1-5), were synthesized using 2H-[1,2,3]triazolo[4,5-c]pyridine (PT) as an auxiliary acceptor, triphenylamine or N,N-bis[4-(hexyloxy)phenyl]aniline as the donor, furan, thiophene, phenyl, or 3-hexylthiophene as the conjugated spacer, and 2 cyanoacrylic acid as the acceptor and anchor as well. They were used as the sensitizers of dye-sensitized solar cells. The NPTn dyes show better performance than the PTNn dyes. Among them, the best efficiency of 7.92% (~96%, N719) was obtained with the NPT5 dye, indicating that the PT core could be used as a new building block for the design of high-performance sensitizers in the future. The negative Mulliken charge from the auxiliary acceptor was found to be useful as a semiempirical index for correlation of the molecular structure with the cell efficiency among structurally similar D-A-pi-A-type congeners. PMID- 26366611 TI - The Quest for Anticancer Vaccines: Deciphering the Fine-Epitope Specificity of Cancer-Related Monoclonal Antibodies by Combining Microarray Screening and Saturation Transfer Difference NMR. AB - The identification of MUC1 tumor-associated Tn antigen (alphaGalpNAc1-O-Ser/Thr) has boosted the development of anticancer vaccines. Combining microarrays and saturation transfer difference NMR, we have characterized the fine-epitope mapping of a MUC1 chemical library (naked and Tn-glycosylated) toward two families of cancer-related monoclonal antibodies (anti-MUC1 and anti-Tn mAbs). Anti-MUC1 mAbs clone VU-3C6 and VU-11E2 recognize naked MUC1-derived peptides and bind GalNAc in a peptide-sequence-dependent manner. In contrast, anti-Tn mAbs clone 8D4 and 14D6 mostly recognize the GalNAc and do not bind naked MUC1-derived peptides. These anti-Tn mAbs show a clear preference for glycopeptides containing the Tn-Ser antigen rather than the Tn-Thr analogue, stressing the role of the underlying amino acid (serine or threonine) in the binding process. The reported strategy can be employed, in general, to unveil the key minimal structural features that modulate antigen-antibody recognition, with particular relevance for the development of Tn-MUC1-based anticancer vaccines. PMID- 26366613 TI - Abstracts The Society of Biomolecular Imaging and Informatics Second Annual Conference September 15-17, 2015 Boston, MA, USA. PMID- 26366612 TI - Posaconazole vs fluconazole or itraconazole for prevention of invasive fungal diseases in patients with acute myeloid leukemia or myelodysplastic syndrome: a cost-effectiveness analysis in an Asian teaching hospital. AB - BACKGROUND: Posaconazole is superior to fluconazole/itraconazole in preventing invasive fungal diseases (IFDs) in neutropenic patients. Whether the higher cost of posaconazole is offset by decreases in IFDs in a given institute requires cost effective analysis encompassing the spectrum of IFDs and socioeconomic factors specific to that geographic area. METHODS: This study performed a cost-effective analysis of posaconazole prophylaxis for IFDs in an Asian teaching hospital, employing decision modeling and data of IFDs and medication costs specific to the institute, in neutropenic patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). RESULTS: In the cost-effectiveness analysis, the higher cost of posaconazole was partially offset by a reduction in the cost of treating IFDs that were prevented, resulting in an incremental cost of 125,954 Hong Kong dollars/16,148 USD per IFD avoided. Over a lifetime horizon, assuming same case fatality rate of IFDs in both groups, use of posaconazole results in 0.07 discounted life years saved. This corresponds to an incremental cost of 116,023 HKD/14,875 USD per life year saved. This incremental cost per life year saved in posaconazole prophylaxis fulfilled the World Health Organization defined threshold for cost-effectiveness. CONCLUSION: Posaconazole prophylaxis was cost effective in Hong Kong. PMID- 26366615 TI - Data in an Information Technology Era. PMID- 26366614 TI - Identification of Bile Duct Paucity in Alagille Syndrome: Using CK7 and EMA Immunohistochemistry as a Reliable Panel for Accurate Diagnosis. AB - Bile duct paucity is the absence or marked reduction in the number of interlobular bile ducts (ILBD) within portal tracts. Its syndromic variant, Alagille syndrome (ALGS), is a multisystem disorder with effects on the liver, cardiovascular system, skeleton, face, and eyes. It is inherited as an autosomal dominant trait due to defects in NOTCH signaling pathway. ALGS is characterized by vanishing ILBD with subsequent chronic obstructive cholestasis in approximately 89% of cases. Cholestasis stimulates formation of new bile ductules through a process of neoductular reaction, making it difficult to evaluate the presence or absence of ILBD. Therefore, finding a method to differentiate clearly between ILBD and the ductular proliferation is essential for accurate diagnosis. A database search identified 28 patients with confirmed diagnosis of ALGS between 1992 and 2014. Additionally, 7 controls were used. A panel of two immunostains, cytokeratin 7 (CK7) and epithelial membrane antigen (EMA), was performed. CK7 highlighted the bile duct epithelium of ILBD and ductular proliferation, while EMA stained only the brush border of ILBD. In our ALGS group, the ratio of EMA positive ILBD to identified portal tracts was 12.6% (range, 0%-41%). However, this same ratio was 95.0% (range, 90%-100%) among control cases (P < 0.001). We propose a panel of two immunostains, CK7 and EMA, to differentiate ILBD from ductular proliferation in patients with cholestasis. With this panel, identification of bile duct paucity can be achieved. Additional studies, including molecular confirmation and clinical correlation, would provide a definitive diagnosis of ALGS. PMID- 26366617 TI - Optimum treatment strategies for polyallergic patients - analysis of a large observational trial. AB - OBJECTIVES: To document the effectiveness and safety of sublingual allergen immunotherapy (SLIT) with a five-grass pollen tablet (Oralair ) and compare different treatment options in a broad, non-selected population of patients in a real-world clinical setting. RESEARCH DESIGN AND METHODS: This was a 2 year, open, prospective, multicenter, single-arm, non-interventional study. Patients with a history of clinically relevant allergic symptoms caused by grass pollen, confirmed by skin prick testing, received treatment with the five-grass pollen tablet. Concomitant treatment with symptomatic medication and/or additional SLIT or subcutaneous immunotherapy (SCIT) was permitted. Twelve-month data are presented here. Effectiveness was assessed comparing a combined rhinoconjunctivitis (RC) score derived from the severity of rhinitis and conjunctivitis symptoms under treatment with retrospective data of the previous year. RESULTS: A total of 1408 patients participated in the study, of whom 434 were children/adolescents and 962 polyallergic. Compared with the grass pollen season preceding five-grass pollen tablet treatment, a statistically significant reduction of 49.9% was achieved in RC score for the total population (p < 0.001), and an improvement in overall health was perceived by 90.9% of patients. The overall population of polyallergic patients derived similar benefits from treatment with the five-grass pollen tablet as monoallergic patients. The percentage reduction in RC score was larger in polyallergic patients taking no additional therapy (60.2%) than in those taking concomitant symptomatic medication (38.1%) or allergen immunotherapy (AIT) (50.8%). Within the last of these groups, RC score improved by 47.6% among patients receiving additional SCIT, versus 54.8% with additional SLIT. Adverse drug reactions, reported in 15.3% of study participants, were mostly local in nature and mild or moderate in intensity. CONCLUSIONS: After 1 year of treatment, polyallergic patients responded similarly to the five-grass pollen tablet as monoallergic patients. For polyallergic patients in whom additional treatment was needed, a second SLIT may be more beneficial than a SCIT or symptomatic co-medication. PMID- 26366618 TI - Special issue: Science and rugby. PMID- 26366619 TI - Monitoring of in-season neuromuscular and perceptual fatigue in youth rugby players. AB - The purpose of this study was to examine both short- and long-term neuromuscular and perceptual fatigue in youth rugby players during a seven-week in-season mesocycle. Eleven male youth rugby players (age 16.9 +/- 0.8 years) were assessed for countermovement jump (CMJ), reactive strength index (RSI) and leg stiffness to monitor neuromuscular performance, together with a well-being questionnaire to monitor perceptual fatigue. Players trained and competed throughout a seven-week block with test variables measured at baseline and 24 h pre- and post-matches played in weeks 1, 4 and 7. Players trained on average 9.7 +/- 1.1 h per week and competed in 10.5 +/- 1.9 games over the seven-week block. Pre- to post-match reductions were significant across all games for CMJ, RSI and well-being (all P < 0.05), ranging from likely to almost certain negative reductions. Well-being and RSI demonstrated non-significant (P < 0.05) unclear or inconsistent changes when comparing pre-match scores to baseline. Significant reductions to baseline were observed pre-match for CMJ (weeks 4 and 7) and stiffness (week 7), representing very likely to almost certain negative long-term decrements. CMJ, RSI and well being were all sensitive to detecting post-match fatigue. Importantly, CMJ and stiffness were sensitive to detecting accumulated fatigue over a seven-week period, whereas RSI and well-being were not. Consequently, either a CMJ or leg stiffness should be monitored to detect long-term, accumulated fatigue in academy rugby players. PMID- 26366616 TI - Current efforts and future prospects in the development of live mycobacteria as vaccines. AB - The development of more effective vaccines against Mycobacterium tuberculosis (Mtb) remains a major goal in the effort to reduce the enormous global burden of disease caused by this pathogen. Whole-cell vaccines based on live mycobacteria with attenuated virulence represent an appealing approach, providing broad antigen exposure and intrinsic adjuvant properties to prime durable immune responses. However, designing vaccine strains with an optimal balance between attenuation and immunogenicity has proven to be extremely challenging. Recent basic and clinical research efforts have broadened our understanding of Mtb pathogenesis and created numerous new vaccine candidates that have been designed to overcome different aspects of immune evasion by Mtb. In this review, we provide an overview of the current efforts to create improved vaccines against tuberculosis based on modifications of live attenuated mycobacteria. In addition, we discuss the use of such vaccine strains as vectors for stimulating protective immunity against other infectious diseases and cancers. PMID- 26366620 TI - Effects of word frequency and visual complexity on eye movements of young and older Chinese readers. AB - Research using alphabetic languages shows that, compared to young adults, older adults employ a risky reading strategy in which they are more likely to guess word identities and skip words to compensate for their slower processing of text. However, little is known about how ageing affects reading behaviour for naturally unspaced, logographic languages like Chinese. Accordingly, to assess the generality of age-related changes in reading strategy across different writing systems we undertook an eye movement investigation of adult age differences in Chinese reading. Participants read sentences containing a target word (a single Chinese character) that had a high or low frequency of usage and was constructed from either few or many character strokes, and so either visually simple or complex. Frequency and complexity produced similar patterns of influence for both age groups on skipping rates and fixation times for target words. Both groups therefore demonstrated sensitivity to these manipulations. But compared to the young adults, the older adults made more and longer fixations and more forward and backward eye movements overall. They also fixated the target words for longer, especially when these were visually complex. Crucially, the older adults skipped words less and made shorter progressive saccades. Therefore, in contrast with findings for alphabetic languages, older Chinese readers appear to use a careful reading strategy according to which they move their eyes cautiously along lines of text and skip words infrequently. We propose they use this more careful reading strategy to compensate for increased difficulty processing word boundaries in Chinese. PMID- 26366621 TI - Tethered agonists: a new mechanism underlying adhesion G protein-coupled receptor activation. AB - The family of adhesion G protein-coupled receptors (aGPCRs) comprises 33 members in the human genome, which are subdivided into nine subclasses. Many aGPCRs undergo an autoproteolytic process via their GPCR Autoproteolysis-INducing (GAIN) domain during protein maturation to generate an N- and a C-terminal fragments, NTF and CTF, respectively. The NTF and CTF are non-covalently reassociated on the plasma membrane to form a single receptor unit. How aGPCRs are activated upon ligand binding remains one of the leading questions in the field of aGPCR research. Recent work from our labs and others shows that ligand binding can remove the NTF from the plasma membrane-bound CTF, exposing a tethered agonist which potently activates downstream signaling. PMID- 26366622 TI - The Past and Future of Occupational Exposure Limits. PMID- 26366623 TI - Prognostic relevance of CD20 expression in peripheral T-cell lymphomas: a multi center retrospective study. PMID- 26366624 TI - Statistical challenges in a regulatory review of cardiovascular and CNS clinical trials. AB - There are several challenging statistical problems identified in the regulatory review of large cardiovascular (CV) clinical outcome trials and central nervous system (CNS) trials. The problems can be common or distinct due to disease characteristics and the differences in trial design elements such as endpoints, trial duration, and trial size. In schizophrenia trials, heavy missing data is a big problem. In Alzheimer trials, the endpoints for assessing symptoms and the endpoints for assessing disease progression are essentially the same; it is difficult to construct a good trial design to evaluate a test drug for its ability to slow the disease progression. In CV trials, reliance on a composite endpoint with low event rate makes the trial size so large that it is infeasible to study multiple doses necessary to find the right dose for study patients. These are just a few typical problems. In the past decade, adaptive designs were increasingly used in these disease areas and some challenges occur with respect to that use. Based on our review experiences, group sequential designs (GSDs) have borne many successful stories in CV trials and are also increasingly used for developing treatments targeting CNS diseases. There is also a growing trend of using more advanced unblinded adaptive designs for producing efficacy evidence. Many statistical challenges with these kinds of adaptive designs have been identified through our experiences with the review of regulatory applications and are shared in this article. PMID- 26366625 TI - Conjunctival Mass as an Initial Presentation of Iatrogenic Orbital Encephalocele. AB - A 46-year-old woman presented with a symptomatic conjunctival mass of the right eye, appearing 2 months after undergoing right frontal craniotomy to excise a meningioma. MRI of the brain revealed a new iatrogenic encephalocele extending into the right temporal orbit. Our opinion is that the conjunctival mass resulted directly from this encephalocele. To date this has been conservatively managed, and we believe this to be the first report of an iatrogenic encephalocele presenting in this manner. PMID- 26366627 TI - The effect of Piriformospora indica on the root development of maize (Zea mays L.) and remediation of petroleum contaminated soil. AB - As the depth of soil petroleum contamination can vary substantially under field conditions, a rhizotron experiment was performed to investigate the influence of endophyte, P. indica, on maize growth and degradation of petroleum components in a shallow and a deep-reaching subsurface layer of a soil. For control, a treatment without soil contamination was also included. The degree in contamination and the depth to which it extended had a strong effect on the growth of the plant roots. Contaminated soil layers severely inhibited root growth thus many roots preferred to bypass the shallow contaminated layer and grow in the uncontaminated soil. While the length and branching pattern of these roots were similar to those of uncontaminated treatment. Inoculation of maize with P. indica could improve root distribution and root and shoot growth in all three contamination treatments. This inoculation also enhanced petroleum degradation in soil, especially in the treatment with deep-reaching contamination, consequently the accumulation of petroleum hydrocarbons (PAHs) in the plant tissues were increased. PMID- 26366626 TI - Hydroxyurea therapy for sickle cell anemia. AB - INTRODUCTION: Sickle cell anemia (SCA) is a severe, inherited hemoglobin disorder affecting 100,000 persons in the US and millions worldwide. Hydroxyurea, a once daily oral medication, has emerged as the primary disease-modifying therapy for SCA. The accumulated body of evidence over 30 years demonstrates that hydroxyurea is a safe and effective therapy for SCA, but hydroxyurea remains underutilized for a variety of reasons. AREAS COVERED: In this review, we summarize the available evidence regarding the pharmacology, clinical, and laboratory benefits, and safety of hydroxyurea therapy for the treatment of SCA. The purpose of this review is to provide the reader a comprehensive understanding of hydroxyurea and to reinforce the fact that hydroxyurea is a safe and effective medication for the treatment of SCA. EXPERT OPINION: In our opinion, hydroxyurea therapy should be considered standard-of-care for SCA, representing an essential component of patient management. Early initiation and broader use of hydroxyurea will alter the natural history of SCA, so affected children can live longer and healthier lives. In addition, hydroxyurea use should be extended to low-resource settings such as sub-Saharan Africa, where the burden of SCA and the need for hydroxyurea is arguably the greatest. PMID- 26366628 TI - Missed opportunities for Hepatitis B vaccination among diabetic patients. AB - Many infectious diseases in adults can be prevented by a 'life-long vaccination strategy'. Hepatitis B disease burden was shown to be higher in diabetic patients. American Advisory Committee on Immunization Practices recommends to vaccinate diabetic patients against hepatitis B since 2011. In this study, we aimed to determine hepatitis B virus serology status to determine the rates of diabetic patients who have indications for hepatitis B vaccination. The electronic database of the hospital was searched to identify adult patients aged above 18 years and with hemoglobin A1C levels of 6.5% or above, who have been seen at General Medicine Outpatient Clinics of a university hospital during a 3 year period. A total of 5187 patients were included in the study. After exclusion of patients with an incomplete serological panel, 1358 patients were included for further analyses. Twenty-nine percent of the patients had indication for hepatitis B vaccination, whereas only 8% were vaccinated. This study showed that nearly one third of patients who had hepatitis B serological data had an indication for hepatitis B vaccination and this is a clear reflection of the need to keep a lifelong vaccination log and inquire vaccination data. PMID- 26366629 TI - Determination of perfluoroalkylated substances (PFASs) in drinking water from the Netherlands and Greece. AB - In the present study 11 perfluoroalkylated substances (PFASs) were analysed in drinking tap water samples from the Netherlands (n = 37) and from Greece (n = 43) by applying LC-MS/MS and isotope dilution. PFASs concentrations above the limit of quantification, LOQ (0.6 ng/l) were detected in 20.9% of the samples from Greece. Total PFAS concentrations ranged between 8) were only rarely detected. In the drinking water samples from the eastern part of the Netherlands, where drinking water is sourced from groundwater reservoirs, no PFASs were detected. This demonstrates that exposure to PFASs through drinking water in the Netherlands is dependent on the source. Additionally, five samples of bottled water from each country were analysed in the current study, with all of them originating from ground wells. In these samples, all PFASs were below the LOQ. PMID- 26366631 TI - A single-chain magnet with a very high blocking temperature and a strong coercive field. AB - Two isostructural 1D complexes, [M(hfac)2NaphNN]n [M = Mn(II) (1) or Co(II) (2); NaphNN = 1-naphthyl nitronylnitroxide], were synthesized and exhibit very strong antiferromagnetic metal-radical exchange coupling. Compound 2 shows slow magnetic relaxation behavior with a high blocking temperature (TB ~ 13.2 K) and a very high coercive field of 49 kOe at 4.0 K. PMID- 26366630 TI - Neurogranin as a Cerebrospinal Fluid Biomarker for Synaptic Loss in Symptomatic Alzheimer Disease. AB - IMPORTANCE: Neurogranin (NGRN) seems to be a promising novel cerebrospinal fluid (CSF) biomarker for synaptic loss; however, clinical, and especially longitudinal, data are sparse. OBJECTIVE: To examine the utility of NGRN, with repeated CSF sampling, for diagnosis, prognosis, and monitoring of Alzheimer disease (AD). DESIGN, SETTING, AND PARTICIPANTS: Longitudinal study of consecutive patients who underwent 2 lumbar punctures between the beginning of 1995 and the end of 2010 within the memory clinic-based Amsterdam Dementia Cohort. The study included 163 patients: 37 cognitively normal participants (mean [SE] age, 64 [2] years; 38% female; and mean [SE] Mini-Mental State Examination [MMSE] score, 28 [0.3]), 61 patients with mild cognitive impairment (MCI) (mean [SE] age, 68 [1] years; 38% female; and mean [SE] MMSE score, 27 [0.3]), and 65 patients with AD (mean [SE] age, 65 [1] years; 45% female; and mean [SE] MMSE score, 22 [0.7]). The mean (SE) interval between lumbar punctures was 2.0 (0.1) years, and the mean (SE) duration of cognitive follow-up was 3.8 (0.2) years. Measurements of CSF NGRN levels were obtained in January and February 2014. MAIN OUTCOME AND MEASURE: Levels of NGRN in CSF samples. RESULTS: Baseline CSF levels of NGRN in patients with AD (median level, 2381 pg/mL [interquartile range, 1651 3416 pg/mL]) were higher than in cognitively normal participants (median level, 1712 pg/mL [interquartile range, 1206-2724 pg/mL]) (P = .04). Baseline NGRN levels were highly correlated with total tau and tau phosphorylated at threonine 181 in all patient groups (all P < .001), but not with Abeta42. Baseline CSF levels of NGRN were also higher in patients with MCI who progressed to AD (median level, 2842 pg/mL [interquartile range, 1882-3950 pg/mL]) compared with those with stable MCI (median level, 1752 pg/mL [interquartile range, 1024-2438 pg/mL]) (P = .004), and they were predictive of progression from MCI to AD (hazard ratio, 1.8 [95% CI, 1.1-2.9]; stratified by tertiles). Linear mixed-model analyses demonstrated that within-person levels of NGRN increased over time in cognitively normal participants (mean [SE] level, 90 [45] pg/mL per year; P < .05) but not in patients with MCI or AD. CONCLUSIONS AND RELEVANCE: Neurogranin is a promising biomarker for AD because levels were elevated in patients with AD compared with cognitively normal participants and predicted progression from MCI to AD. Within person levels of NGRN increased in cognitively normal participants but not in patients with later stage MCI or AD, which suggests that NGRN may reflect presymptomatic synaptic dysfunction or loss. PMID- 26366633 TI - Theoretical design of the cyclic lipopeptide nanotube as a molecular channel in the lipid bilayer, molecular dynamics and quantum mechanics approach. AB - In this article, cyclic peptides (CP) with lipid substituents were theoretically designed. The dynamical behavior of the CP dimers and the cyclic peptide nanotube (CPNT) without lipid substituents in the solution (water and chloroform) during the 50 ns molecular dynamic (MD) simulations has been investigated. As a result, the CP dimers and CPNT in a non-polar solvent are more stable than in a polar solvent and CPNT is a good container for non-polar small molecules such as chloroform. The effect of the lipid substituents on the CP dimers and CPNT has been investigated in the next stage of our studies. Accordingly, these substituents increase the stability of the CP dimers and CPNT, significantly, in polar solvents. MM-PBSA and MM-GBSA calculations confirm that substitution has an important effect on the stability of the CP dimers and CPNT. Finally, the dynamical behavior of CPNT with lipid substituents in a fully hydrated DMPC bilayer shows the high ability of this structure for molecule transmission across the lipid membrane. This structure is stable enough to be used as a molecular channel. DFT calculations on the CP dimers in the gas phase, water and chloroform, indicate that H-bond formation is the driving force for dimerization. CP dimers are more stable in the gas phase in comparison to in solution. HOMO LUMO orbital analysis indicates that the interaction of the CP units in the dimer structures is due to the molecular orbital interactions between the NH and CO groups. PMID- 26366632 TI - Nitric oxide and oxidative stress in placental explant cultures. AB - Placental explant culture, and cellular cytolysis and cellular differentiation have been previously studied. However, oxidative stress and nitric oxide profiles have not been evaluated in these systems. The aim of this study was to determine the release of lipid peroxidation and nitric oxide from placental explants cultured over a seven day period. Placental explants were maintained for seven days in culture and the medium was changed every 24 hours. The response was assessed in terms of syncytiotrophoblast differentiation (human chorionic gonadotropin, hCG), cellular cytolysis (lactate dehydrogenase, LDH), oxidative stress (thiobarbituric acid reactive substances, TBARS), and nitric oxide (NO). Levels of hCG increased progressively from day two to attain its highest level on days four and five after which it decreased gradually. In contrast, the levels of LDH, TBARS, and NO were elevated in the early days of placental culture when new syncytiotrophoblast from cytotrophoblast were forming and also in the last days of culture when tissue was declining. In conclusion, the levels of NO and lipid peroxidation follow a pattern similar to LDH and contrary to hCG. Future placental explant studies to evaluate oxidative stress and NO should consider the physiological changes inherent during the time of culture. PMID- 26366634 TI - Production of chiral compounds using immobilized cells as a source of biocatalysts. AB - The importance of chiral compounds in all fields of technology and life sciences is shown. Small chiral molecules are mainly used as building blocks in the synthesis of more complex and functionalized compounds. Nature creates and imposes stereoselectivity by means of enzymes, which are highly efficient biocatalysts. The use of whole cells as a biocatalyst source is a promising strategy for avoiding some drawbacks associated with the use of pure enzymes, especially their high cost. The use of free cells is also challenging, since cell lysis can also occur under the reaction conditions. However, cell immobilization has been employed to increase the catalytic potential of enzymes by extending their lifetimes in organic solvents and non-natural environments. Besides, immobilized cells maintain their biocatalytic performance for several reaction cycles. Considering the above-mentioned arguments, several authors have synthesized different classes of chiral compounds such as alcohols, amines, carboxylic acids, amides, sulfides and lactones by means of immobilized cells. Our aim was to discuss the main aspects of the production of chiral compounds using immobilized cells as a source of biocatalysts, except under fermentation conditions. PMID- 26366635 TI - Understanding amygdala responsiveness to fearful expressions through the lens of psychopathy and altruism. AB - Because the face is the central focus of human social interactions, emotional facial expressions provide a unique window into the emotional lives of others. They play a particularly important role in fostering empathy, which entails understanding and responding to others' emotions, especially distress-related emotions such as fear. This Review considers how fearful facial as well as vocal and postural expressions are interpreted, with an emphasis on the role of the amygdala. The amygdala may be best known for its role in the acquisition and expression of conditioned fear, but it also supports the perception and recognition of others' fear. Various explanations have been supplied for the amygdala's role in interpreting and responding to fearful expressions. They include theories that amygdala responses to fearful expressions 1) reflect heightened vigilance in response to uncertain danger, 2) promote heightened attention to the eye region of faces, 3) represent a response to an unconditioned aversive stimulus, or 4) reflect the generation of an empathic fear response. Among these, only empathic fear explains why amygdala lesions would impair fear recognition across modalities. Supporting the possibility of a link between fundamental empathic processes and amygdala responses to fear is evidence that impaired fear recognition in psychopathic individuals results from amygdala dysfunction, whereas enhanced fear recognition in altruistic individuals results from enhanced amygdala function. Empathic concern and caring behaviors may be fostered by sensitivity to signs of acute distress in others, which relies on intact functioning of the amygdala. PMID- 26366636 TI - Investigating proteasome inhibitors as potential adjunct therapies for experimental cerebral malaria. AB - Aside from antimalarials, there is currently no treatment for cerebral malaria, a fulminant neurological complication of P. falciparum infection that is a leading cause of death in African children. In the mouse model of cerebral malaria, cross presentation of parasite antigens by brain endothelial cells is thought to be a crucial late step in pathogenesis. We have investigated three proteasome inhibitors as potential adjunct therapies: bortezomib, carfilzomib and ONX-0914. Only carfilzomib, an irreversible inhibitor of both constitutive proteasomes and immunoproteasomes, was able to inhibit cross-presentation of malaria antigen by murine brain endothelial cells in vitro. To mimic the clinical setting, carfilzomib was co-administered with artesunate only when infected mice exhibited neurological defects. However, there was no improvement in survival compared to artesunate monotherapy. The treatment failure was explained by the inability of daily or twice daily bolus doses of carfilzomib to inhibit cross-presentation by brain endothelial cells in vivo. We also report here that bortezomib, which has been associated with neurological adverse events, accelerated death in ECM infected mice. Future investigations of proteasome inhibitors for modulating cross-presentation during malaria infection should focus on sustained and targeted delivery to brain endothelial cells. PMID- 26366637 TI - Mental disorders and mortality: so many publications, so little change. PMID- 26366638 TI - Differentiating the extent of cartilage repair in rabbit ears using nonlinear optical microscopy. AB - Nonlinear optical microscopy (NLOM) was used as a noninvasive and label-free tool to detect and quantify the extent of the cartilage recovery. Two cartilage injury models were established in the outer ears of rabbits that created a different extent of cartilage recovery based on the presence or absence of the perichondrium. High-resolution NLOM images were used to measure cartilage repair, specifically through spectral analysis and image texture. In contrast to a wound lacking a perichondrium, wounds with intact perichondria demonstrated significantly larger TPEF signals from cells and matrix, coarser texture indicating the more deposition of type I collagen. Spectral analysis of cells and matrix can reveal the matrix properties and cell growth. In addition, texture analysis of NLOM images showed significant differences in the distribution of cells and matrix of repaired tissues with or without perichondrium. Specifically, the decay length of autocorrelation coefficient based on TPEF images is 11.2 +/- 1.1 in Wound 2 (with perichondrium) and 7.5 +/- 2.0 in Wound 1 (without perichondrium), indicating coarser image texture and faster growth of cells in repaired tissues with perichondrium (p < 0.05). Moreover, the decay length of autocorrelation coefficient based on collagen SHG images also showed significant difference between Wound 2 and 1 (16.2 +/- 1.2 vs. 12.2 +/- 2.1, p < 0.05), indicating coarser image texture and faster deposition of collagen in repaired tissues with perichondrium (Wound 2). These findings suggest that NLOM is an ideal tool for studying cartilage repair, with potential applications in clinical medicine. NLOM can capture macromolecular details and distinguish between different extents of cartilage repair without the need for labelling agents. PMID- 26366640 TI - Protecting-Group-Free Enantioselective Synthesis of (-)-Pallavicinin and (+) Neopallavicinin. AB - The first enantioselective synthesis of (-)-pallavicinin and (+)-neopallavicinin has been achieved in 15 steps. The described synthesis avoids protecting-group manipulations by synthesis designs predicated on highly chemo- and stereoselective transformations. Highlights of the synthesis include a palladium catalyzed enantioselective decarboxylative allylation to form the chiral all carbon quaternary stereocenter, a palladium-catalyzed oxidative cyclization to assemble the [3.2.1]-bicyclic moiety, and an unprecedented LiBHEt3-induced fragmentation/protonation of an alpha-hydroxy epoxide to form the alpha-furan ketone with the desired configuration. PMID- 26366639 TI - Psychosocial Predictors of Mortality Following Lung Transplantation. AB - Lung transplantation has become an increasingly common treatment for patients with end-stage lung disease. Few studies have examined psychosocial risk factors for mortality in transplant recipients, despite evidence suggesting that elevated levels of negative affect are associated with greater mortality following major cardiac surgery. We therefore examined the relationship between negative affect early after lung transplantation and long-term survival in a sample of 132 lung transplant recipients (28 cystic fibrosis, 64 chronic obstructive pulmonary disease, 26 idiopathic pulmonary fibrosis, 14 other) followed for up to 13.5 years (median 7.4 years) following transplantation. Patients underwent both medical and psychosocial assessments 6 months following transplantation, which included the Beck Depression Inventory-II (BDI-II), Spielberger Anxiety Inventory, and General Health Questionnaire (GHQ). Over the course of follow-up, 80 (61%) participants died. Controlling for demographic factors, native lung disease, disease severity, family income, education level, social support, and frequency of posttransplant rejection, elevated symptoms of depression (BDI-II: HR = 1.31, p = 0.011) and distress (GHQ: HR = 1.28, p = 0.003) were associated with increased mortality. Higher levels of depression and general distress, but not anxiety, measured 6 months following lung transplantation are associated with increased mortality, independent of background characteristics and medical predictors. PMID- 26366641 TI - Hippocampal-DMN disconnectivity in MS is related to WM lesions and depression. AB - The hippocampus is part of the default-mode network (DMN) and is functionally hit early in multiple sclerosis (MS). Hippocampal and DMN dysfunctions have been associated with depression, both in patients with MS and in major depressive disorders. We hypothesized that white matter lesions may contribute, through a disconnection mechanism, to hippocampal dysfunction. To test this, we assessed the relationship between hippocampal resting-state (RS) functional connectivity (FC) abnormalities with brain T2 lesion volumes and the presence and severity of depression. Structural and RS fMRI images were acquired from 69 patients with cognitively intact MS and 42 matched healthy controls (HC). Depression was quantified using the Montgomery-Asberg Depression Rating Scale. Seed-voxel hippocampal RS FC was assessed. SPM8 was used for between-group comparisons and correlation analysis between RS FC abnormalities with clinical and structural MRI variables. Compared to HC, patients with MS showed a significant atrophy of the whole brain and left hippocampus (P < 0.001), and a distributed pattern of decreased RS FC between the hippocampi and several cortical-subcortical regions, which were mostly located within the DMN. Reduced hippocampal RS FC with regions of the DMN was strongly correlated with higher T2 lesion volume, longer disease duration, and the severity of depression and disability. In patients with cognitively preserved MS, brain focal WM lesions are related to the functional integration of the hippocampus to other brain regions of the DMN, suggesting a disconnection syndrome. Such a disruption of hippocampal RS FC is likely to contribute to the occurrence of depression and to clinical disability. PMID- 26366642 TI - [Imaging of the Lacrimal Gland and the Lacrimal Drainage System]. AB - A large number of different neoplastic, infective and autoimmunologic diseases can affect the lacrimal gland. Thorough imaging examinations can help to characterize lesions to narrow down possible differential diagnoses. Diseases of the lacrimal drainage system, especially obstructions with constant epiphora are often very irritating for the patients. Imaging examinations can assist in selecting the adequate therapy in interdisciplinary consensus. Moreover, interventional-radiological therapy (e. g. balloon-dacryocystoplasty) is an attractive minimally-invasive treatment alternative. PMID- 26366643 TI - [Preventing and managing complications]. PMID- 26366644 TI - DynaMet: a fully automated pipeline for dynamic LC-MS data. AB - Dynamic isotope labeling data provides crucial information about the operation of metabolic pathways and are commonly generated via liquid chromatography-mass spectrometry (LC-MS). Metabolome-wide analysis is challenging as it requires grouping of metabolite features over different samples. We developed DynaMet for fully automated investigations of isotope labeling experiments from LC-high resolution MS raw data. DynaMet enables untargeted extraction of metabolite labeling profiles and provides integrated tools for expressive data visualization. To validate DynaMet we first used time course labeling data of the model strain Bacillus methanolicus from (13)C methanol resulting in complex spectra in multicarbon compounds. Analysis of two biological replicates revealed high robustness and reproducibility of the pipeline. In total, DynaMet extracted 386 features showing dynamic labeling within 10 min. Of these features, 357 could be fitted by implemented kinetic models. Feature identification against KEGG database resulted in 215 matches covering multiple pathways of core metabolism and major biosynthetic routes. Moreover, we performed time course labeling experiment with Escherichia coli on uniformly labeled (13)C glucose resulting in a comparable number of detected features with labeling profiles of high quality. The distinct labeling patterns of common central metabolites generated from both model bacteria can readily be explained by one versus multicarbon compound metabolism. DynaMet is freely available as an extension package for Python based eMZed2, an open source framework built for rapid development of LC-MS data analysis workflows. PMID- 26366645 TI - Channel analysis for single photon underwater free space quantum key distribution. AB - We investigate the optical absorption and scattering properties of underwater media pertinent to our underwater free space quantum key distribution (QKD) channel model. With the vector radiative transfer theory and Monte Carlo method, we obtain the attenuation of photons, the fidelity of the scattered photons, the quantum bit error rate, and the sifted key generation rate of underwater quantum communication. It can be observed from our simulations that the most secure single photon underwater free space QKD is feasible in the clearest ocean water. PMID- 26366646 TI - How psychophysical methods influence optimizations of color difference formulas. AB - For developing color difference formulas, there are several choices to be made on the psychophysical method used for gathering visual (observer) data. We tested three different psychophysical methods: gray scales, constant stimuli, and two alternative forced choice (2AFC). Our results show that when using gray scales or constant stimuli, assessments of color differences are biased toward lightness differences. This bias is particularly strong in LCD monitor experiments, and also present when using physical paint samples. No such bias is found when using 2AFC. In that case, however, observer responses are affected by other factors that are not accounted for by current color difference formulas. For accurate prediction of relative color differences, our results show, in agreement with other works, that modern color difference formulas do not perform well. We also investigated if the use of digital images as presented on LCD displays is a good alternative to using physical samples. Our results indicate that there are systematic differences between these two media. PMID- 26366647 TI - Parameter error analysis of single-lens prism-based stereovision system. AB - In this paper, the quantization error and parameters of the single-lens prism based stereovision system are studied in detail. Each image captured using this system can be divided into two subimages on the left and right, and these subimages are generated by two virtual cameras that are produced by the biprism. This stereovision system is equivalent to the conventional two-camera system and the two subimages captured have disparity that can be used to reconstruct the 3D scene. The relative range error of this system is studied with respect to the system parameters, which gives us a better way to quantify the range resolution of the system and enables the selection of system parameters to become easier. PMID- 26366648 TI - Evolution properties of a Laguerre-Gaussian correlated Schell-model beam propagating in uniaxial crystals orthogonal to the optical axis. AB - Analytical expressions for the cross-spectral density function and the second order moments of a Laguerre-Gaussian correlated Schell-model (LGCSM) beam propagating in uniaxial crystals orthogonal to the optical axis are derived. Based on the formulas derived, we study the propagation properties, such as beam irradiance, beam diameters, and the spectral degree of coherence, of a LGCSM beam inside uniaxial crystals in detail. The effect of the initial beam parameters (mode order and spatial coherence length) and the parameters of the uniaxial crystals on the evolution properties of a LGCSM beam is revealed through numerical examples. The uniaxial crystals provide one way to modulate the properties of a LGCSM beam. PMID- 26366649 TI - Reference data set for camera spectral sensitivity estimation. AB - In this article, we describe a spectral sensitivity measurement procedure at the National Physical Laboratory, London, with the aim of obtaining ground truth spectral sensitivity functions for Nikon D5100 and Sigma SD1 Merill cameras. The novelty of our data is that the potential measurement errors are estimated at each wavelength. We determine how well the measured spectral sensitivity functions represent the actual camera sensitivity functions (as a function of wavelength). The second contribution of this paper is to test the performance of various leading sensor estimation techniques implemented from the literature using measured and synthetic data and also evaluate them based on ground truth data for the two cameras. We conclude that the estimation techniques tested are not sufficiently accurate when compared with our measured ground truth data and that there remains significant scope to improve estimation algorithms for spectral estimation. To help in this endeavor, we will make all our data available online for the community. PMID- 26366650 TI - Efficient propagation-inside-layer expansion algorithm for solving the scattering from three-dimensional nested homogeneous dielectric bodies with arbitrary shape. AB - This paper deals with the evaluation of electromagnetic scattering from a three dimensional structure consisting of two nested homogeneous dielectric bodies with arbitrary shape. The scattering problem is formulated in terms of a set of Poggio Miller-Chang-Harrington-Wu integral equations that are afterwards converted into a system of linear equations (impedance matrix equation) by applying the Galerkin method of moments (MoM) with Rao-Wilton-Glisson basis functions. The MoM matrix equation is then solved by deploying the iterative propagation-inside-layer expansion (PILE) method in order to obtain the unknown surface current densities, which are thereafter used to handle the radar cross-section (RCS) patterns. Some numerical results for various structures including canonical geometries are presented and compared with those of the FEKO software in order to validate the PILE-based approach as well as to show its efficiency to analyze the full polarized RCS patterns. PMID- 26366651 TI - Numerical scheme for the modal method based on subsectional Gegenbauer polynomial expansion: application to biperiodic binary grating. AB - The modal method based on Gegenbauer polynomials (MMGE) is extended to the case of bidimensional binary gratings. A new concept of modified polynomials is introduced in order to take into account boundary conditions and also to make the method more flexible in use. In the previous versions of MMGE, an undersized matrix relation is obtained by solving Maxwell's equations, and the boundary conditions complement this undersized system. In the current work, contrary to this previous version of the MMGE, boundary conditions are incorporated into the definition of a new basis of polynomial functions, which are adapted to the boundary value problem of interest. Results are successfully compared for both metallic and dielectric structures to those obtained from the modal method based on Fourier expansion (MMFE) and MMFE with adaptative spatial resolution. PMID- 26366652 TI - Compact multi-aperture imaging with high angular resolution. AB - Previous reports have demonstrated that it is possible to emulate the imaging function of a single conventional lens with an N*N array of identical lenslets to provide an N-fold reduction in imaging-system track length. This approach limits the application to low-resolution imaging. We highlight how using an array of dissimilar lenslets, with an array width that can be much wider than the detector array, high-resolution super-resolved imaging is possible. We illustrate this approach with a ray-traced design and optimization of a long-wave infrared system employing a 3*3 array of freeform lenslets to provide a fourfold reduction in track length compared to a baseline system. Simulations of image recovery show that recovered image quality is comparable to that of the baseline system. PMID- 26366653 TI - Waveguide mode in the box with an extraordinary flat dispersion curve. AB - The extraordinary flattening of the dispersion curve of the so-called cavity resonator integrated guided-mode resonance filters (CRIGFs) is analyzed and explained as due to the intramode coupling imposed by the external Bragg resonators. CRIGFs are composed of a grating coupler (guided-mode resonance filter, GMRF) put between two distributed Bragg reflectors (DBRs). They form a cavity box in which the excited guided mode is confined. This confinement provides resonances with small spectral width (smaller than 1 nm for optical wavelengths) and extraordinary wide angular acceptance (several degrees). At a first glance, one may think that similar performances could be obtained while putting the GMRF and the DBR one above the other, forming a so-called "doubly periodic" grating, as in this configuration also the DBR confines the mode. Yet, the angular acceptance of CRIGFs is an order of magnitude greater than in classical gratings, even with complex pattern. The aim of the present paper is to identify the phenomenon responsible for the extraordinary large angular acceptance of CRIGFs. We numerically calculate, for the first time to the best of our knowledge, the dispersion curve of the mode excited in the CRIGF. The dispersion curve shows a flat part, where the resonance wavelength is quasi independent of the angle of incidence, and the flattening grows with the width of the Bragg reflector. We develop an approximate coupled four-wave model, which predicts the extraordinary flattening as a consequence of an additional coupling of the waveguide modes of the GMRF provided by the Bragg grating, that does not exist in the "doubly periodic" gratings. PMID- 26366654 TI - Thermal-to-visible face recognition using partial least squares. AB - Although visible face recognition has been an active area of research for several decades, cross-modal face recognition has only been explored by the biometrics community relatively recently. Thermal-to-visible face recognition is one of the most difficult cross-modal face recognition challenges, because of the difference in phenomenology between the thermal and visible imaging modalities. We address the cross-modal recognition problem using a partial least squares (PLS) regression-based approach consisting of preprocessing, feature extraction, and PLS model building. The preprocessing and feature extraction stages are designed to reduce the modality gap between the thermal and visible facial signatures, and facilitate the subsequent one-vs-all PLS-based model building. We incorporate multi-modal information into the PLS model building stage to enhance cross-modal recognition. The performance of the proposed recognition algorithm is evaluated on three challenging datasets containing visible and thermal imagery acquired under different experimental scenarios: time-lapse, physical tasks, mental tasks, and subject-to-camera range. These scenarios represent difficult challenges relevant to real-world applications. We demonstrate that the proposed method performs robustly for the examined scenarios. PMID- 26366655 TI - Intensity-symmetric Airy beams. AB - Theoretical, numerical, and experimental research on a novel family of Airy beams in rectangular coordinates having a symmetric transverse pattern of light intensity is presented. The intensity-symmetric Airy beams include both the symmetric Airy beam whose field amplitude is an even function of the transverse coordinates and the antisymmetric Airy beam whose field amplitude is an odd function of such coordinates. The theoretical foundations are based on the relationship of the symmetries of the spectral phase with the cosine and sine Fourier transforms. These beams are analyzed in a propagation range also including the region preceding the Fourier plane. These beams exhibit autofocusing, collapse, self-bending, and reversal propagation. Moreover, the intensity distribution is strongly asymmetric with respect to the Fourier plane. All these peculiar features were not reported for other classes of paraxial beams in a rectangular frame. The experimental generation of intensity-symmetric Airy beams is demonstrated supporting the theoretical predictions. Possible applications in planar waveguide writing and optical trapping are also discussed. PMID- 26366656 TI - Correlation between the phase and the log-amplitude of a wave through vertical atmospheric propagation. AB - Expressions of the correlation between the log-amplitude and the phase of a wavefront propagating through atmospheric turbulence are presented. These expressions are useful to evaluate the feasibility of proposed methods to increase the confidence level of the detection of faint transient astronomical objects. The properties of the derived angular correlation functions are discussed using usual synthetic turbulence profiles. The close formulation between the phase and the log-amplitude allows an analytic formulation in the Rytov approximation. Equations contain the product of an arbitrary number of hypergeometric functions that are evaluated using the Mellin transforms integration method. PMID- 26366657 TI - Phase retrieval of reflection and transmission coefficients from Kramers-Kronig relations. AB - Analytic and passivity properties of reflection and transmission coefficients of thin-film multilayered stacks are investigated. Using a rigorous formalism based on the inverse Helmholtz operator, properties associated with the causality principle and passivity are established when both the temporal frequency and spatial wave vector are continued in the complex plane. This result extends the range of situations where the Kramers-Kronig relations can be used to deduce the phase from the intensity. In particular, it is rigorously shown that the Kramers Kronig relations for reflection and transmission coefficients remain valid for all fixed angles of incidence. Possibilities for exploiting the new relationships are discussed and numerically tested. PMID- 26366658 TI - Variant of the region-scalable fitting energy for image segmentation. AB - This paper presents a variant of the level set function based on region-scalable fitting (RSF) model for segmenting a given image into different parts. In consideration of the image local characteristics, the RSF model can efficiently and effectively segment images with intensity inhomogeneity. Instead of utilizing n level set functions to define up to 2n phases in the RSF model, our method presents a piecewise constant level set formulation for image segmentation and each phase is represented by a unique constant value. In addition, our model avoids different segmentation results caused by different initializations. The energy functional of our method is locally differentiable and convex because we do not use the nondifferentiable Heaviside and Delta functions. Comparative experiment results demonstrate that our method is much more computationally efficient. Moreover, our algorithm is robust against destructive noise. PMID- 26366659 TI - Time-domain solution to the radiative transfer equation in an infinite turbid medium with linearly anisotropic scattering. AB - A time-dependent solution of the transport equation with an instantaneous point source is considered by the multiple collision method developed by Kholin [Zh. Vych. Mat. i Mat. Fys.4, 1126 (1964)]. For a linear phase function, Kholin's solution is found to be considerably simplified and can be expressed through a single integral. The shape of the time-dependent angle-averaged scattering intensity is shown to depend on the distance from the source. For short distances, the angle-averaged scattering intensity decays monotonically with time. For longer distances, the angle-averaged intensity exhibits two peaks. The first infinite peak occurs at the wavefront and is followed by a narrow decaying tail. The second peak occurs at approximately the position of the diffusion peak but is higher than the diffusion peak. At large distances, the shape of the intensity after the wavefront arrival is well approximated by the diffusion shape. Good agreement with Monte Carlo simulation is demonstrated. PMID- 26366660 TI - Direct stigmatic imaging with curved surfaces. AB - We study the possibilities of direct (using one intersection with each light ray) stigmatic imaging with a curved surface that can change ray directions in an arbitrary way. By purely geometric arguments we show that the only possible case of such imaging is the trivial one where the image of any point is identical to the point itself and the surface does not perform any change of the ray direction at all. We also discuss an example of a curved surface which performs indirect stigmatic imaging after twice intersecting each light ray. PMID- 26366661 TI - High-resolution ghost imaging experiments with cosh-Gaussian modulated incoherent sources. AB - We experimentally demonstrate that ghost imaging (GI) quality can be significantly improved by modulating the incoherent Gaussian sources with hyperbolic cosine functions. In our experiments, a source with desired cosh Gaussian intensity distribution can be generated by a programmable spatial light modulator, and is used in the GI setup to obtain high quality ghost images. The influences of the hyperbolic cosine parameter on the point-spread function and the GI quality have been investigated experimentally and interpreted theoretically. Our experimental results show that the resolution of ghost images can be obviously enhanced with cosh-Gaussian modulated incoherent sources. The kind of source-shaping technique proposed in this paper is a high-efficiency method to improve the GI quality and may be very useful for the GI applications. PMID- 26366662 TI - Modeling of optical wireless scattering communication channels over broad spectra. AB - The air molecules and suspended aerosols help to build non-line-of-sight (NLOS) optical scattering communication links using carriers from near infrared to visible light and ultraviolet bands. This paper proposes channel models over such broad spectra. Wavelength dependent Rayleigh and Mie scattering and absorption coefficients of particles are analytically obtained first. They are applied to the ray tracing based Monte Carlo method, which models the photon scattering angle from the scatterer and propagation distance between two consecutive scatterers. Communication link path loss is studied under different operation conditions, including visibility, particle density, wavelength, and communication range. It is observed that optimum communication performances exist across the wavelength under specific atmospheric conditions. Infrared, visible light and ultraviolet bands show their respective features as conditions vary. PMID- 26366663 TI - Ellipse fitting for interferometry. Part 3: dynamic method. AB - We describe a dynamically based method for fitting an ellipse to noisy data, which has for interferometric applications a number of advantages over conventional static methods (originally developed for image processing). Our method relies on the observation that each data point belongs to an ordered time series and thus has a well-defined phase parameter. We demonstrate that for real experimental data it can achieve much greater accuracy than static methods. The precision of the fit is limited only by the statistical reliability of the data, even in extreme cases such as ellipses with a minor axis smaller than the measurement noise. PMID- 26366664 TI - Antisense RNA-based High-Throughput Screen System for Directed Evolution of Quorum Quenching Enzymes. AB - Quorum quenching (QQ) enzymes, which disrupt the quorum sensing signaling process, have attracted considerable attention as new antimicrobial agents. However, their low catalytic efficiency for quorum sensing molecules remains a challenge. Herein, we present an antisense RNA-based high-throughput screen system for directed evolution of a quorum quenching enzyme. The screening system was constructed by incorporating an antisense RNA (RyhB) into a synthetic module to quantitatively regulate the expression of a reporter gene fused with a sense RNA (sodB). To control the expression of a reporter gene in response to the catalytic activity of a quorum quenching enzyme, the region of interaction and mode between a pair of antisense (RyhB) and sense (sodB) RNAs was designed and optimized through the prediction of the secondary structure of the RNA pair. The screening system constructed was shown to lead to a significant reduction in the false-positive rate (average 42%) in the screening of N-acyl-homoserine lactonase (AiiA) with increased catalytic activity, resulting in a true-positive frequency of up to 76%. The utility and efficiency of the screening system were demonstrated by selecting an AiiA with 31-fold higher catalytic efficiency than the wild-type in three rounds of directed evolution. The present approach can be widely used for the screening of quorum quenching enzymes with the desired catalytic property, as well as for a synthetic network for a stringent regulation of the gene expression. PMID- 26366665 TI - Randomized trial of cesarean vs vaginal delivery for effects on the pelvic floor in squirrel monkeys. AB - BACKGROUND: Vaginal delivery is a risk factor in pelvic floor disorders. We previously described changes in the pelvic floor associated with pregnancy and parturition in the squirrel monkey, a species with a humanlike pattern of spontaneous age- and parity-associated pelvic organ prolapse. OBJECTIVE: The potential to prevent or diminish these changes with scheduled cesarean delivery (CD) has not been evaluated. In a randomized, controlled trial, we compared female squirrel monkeys undergoing spontaneous vaginal delivery with those undergoing scheduled primary CD for pelvic floor muscle volumes, muscle contrast changes, and dynamic effects on bladder neck position. STUDY DESIGN: Levator ani, obturator internus, and coccygeus (COC) muscle volumes and contrast uptake were assessed by magnetic resonance imaging in 20 nulliparous females examined prior to pregnancy, a few days after delivery, and 3 months postpartum. The position of bladder neck relative to bony reference line also was assessed with abdominal pressure using dynamic magnetic resonance imaging. RESULTS: Baseline measurements of 10 females randomly assigned to scheduled primary CD were not different from those of 10 females assigned to spontaneous vaginal delivery. Levator ani and obturator internus muscle volumes did not differ between groups, while volumes were reduced (P < .05) in the observation immediately after pregnancy. The COC muscles increased (P < .05) immediately after delivery for females in the spontaneous vaginal delivery group, but not for females in the scheduled CD group. Position of the bladder neck descended (P < .05) by 3 months postpartum in both groups. CONCLUSION: Scheduled CD diminishes changes in COC muscle volume and contrast reported to be associated with spontaneous vaginal delivery in squirrel monkeys. However, pelvic support of the bladder was not protected by this intervention suggesting that effects of pregnancy and delivery are not uniformly prevented by this procedure. PMID- 26366666 TI - Rates of colpopexy and colporrhaphy at the time of hysterectomy for prolapse. AB - BACKGROUND: It has been shown that addressing apical support at the time of hysterectomy for pelvic organ prolapse (POP) reduces recurrence and reoperation rates. In fact, national guidelines consider hysterectomy alone to be inadequate treatment for POP. Despite this, anterior and posterior colporrhaphy are frequently performed without a colpopexy procedure and hysterectomy alone is often utilized for treatment of prolapse. OBJECTIVE: The objectives of this study were to: (1) determine rates of concomitant procedures for POP in hysterectomies performed with POP as an indication, (2) identify factors associated with performance of a colpopexy at the time of hysterectomy for POP, and (3) identify the influence of surgical complexity on perioperative complication rates. STUDY DESIGN: This is a retrospective cohort study of hysterectomies performed for POP from Jan. 1, 2013, through May 7, 2014, in a statewide surgical quality database. Patients were stratified based on procedures performed: hysterectomy alone, hysterectomy with colporrhaphy and without apical suspension, and hysterectomy with colpopexy with or without colporrhaphy. Demographics, medical history and intraoperative care, and perioperative care were compared between the groups. Multivariable logistic regression models were created to identify factors independently associated with use of colpopexy and factors associated with increased rates of postoperative complications. RESULTS: POP was an indication in 1557 hysterectomies. Most hysterectomies were vaginal (59.6%), followed by laparoscopic or robotic (34.1%), and abdominal (6.2%). Hysterectomy alone was performed in 43.1% (95% confidence interval [CI], 40.6-45.6) of cases, 32.8% (95% CI, 30.4-35.1) had a colporrhaphy without colpopexy, and 24.1% (95% CI, 22-26.3) had a colpopexy with or without colporrhaphy. Use of colpopexy was independently associated with patient age >40 years, POP as the only indication for surgery (odd ratio [OR], 1.6; 95% CI, 1.185-2.230), laparoscopic surgery (OR, 3.2; 95% CI, 2.860-5.153), and a surgeon specializing in urogynecology (OR, 8.2; 95% CI, 5.156-12.923). The overall perioperative complication rate was 6.6%, with the majority being considered minor. Complications were more likely when the procedure was performed with an abdominal approach (OR, 2.3; 95% CI, 1.088 4.686), with the use of a colpopexy procedure (OR, 3.1; 95% CI, 1.840-5.194), and by a surgeon specializing in urogynecology (OR, 2.2; 95% CI, 1.144-4.315). CONCLUSION: Colpopexy and colporrhaphy may be underutilized and are potential targets for quality improvement. Performance of additional procedures at the time of hysterectomy increased the rate of perioperative complications. Long-term consequences of these surgical practices deserve additional study. PMID- 26366667 TI - Positive selection of AS3MT to arsenic water in Andean populations. AB - Arsenic is a carcinogen associated with skin lesions and cardiovascular diseases. The Colla population from the Puna region in Northwest Argentinean is exposed to levels of arsenic in drinking water exceeding the recommended maximum by a factor of 20. Yet, they thrive in this challenging environment since thousands of years and therefore we hypothesize strong selection signatures in genes involved in arsenic metabolism. We analyzed genome-wide genotype data for 730,000 loci in 25 Collas, considering 24 individuals of the neighbouring Calchaquies and 24 Wichi from the Gran Chaco region in the Argentine province of Salta as control groups. We identified a strong signal of positive selection in the main arsenic methyltransferase AS3MT gene, which has been previously associated with lower concentrations of the most toxic product of arsenic metabolism monomethylarsonic acid. This study confirms recent studies reporting selection signals in the AS3MT gene albeit using different samples, tests and control populations. PMID- 26366669 TI - A new practical guide to the Luria-Delbruck protocol. AB - Since 2000 several review papers have been published about the analysis of experimental data obtained using the Luria-Delbruck protocol. These timely papers cleared much of the confusion surrounding various methods for estimating or comparing mutation rates. As a result, today the fluctuation test is more widely applied with much improved accuracy. The present paper provides guidelines on a few remaining problems that continue to baffle mutation researchers. Among the issues addressed are incomplete plating, relative fitness, and comparison of experiments where average final cell population sizes differ. It also offers a fresh view on the estimation methods that are based on the sample median. PMID- 26366670 TI - Pulmonary Artery Pseudoaneurysm: A Rare Cause of Hemoptysis in a Child. AB - Aneurysms and pseudoaneurysms of pulmonary vasculature are uncommon occurrences that contribute to mortality and morbidity, without timely diagnosis and intervention. We report a fatal massive hemoptysis in a child due to a consolidation-related pulmonary arterial pseudoaneurysm, an extremely rare phenomenon. PMID- 26366671 TI - The complete mitochondrial genome of Strongylus equinus (Chromadorea: Strongylidae): Comparison with other closely related species and phylogenetic analyses. AB - The roundworms of genus Strongylus are the common parasitic nematodes in the large intestine of equine, causing significant economic losses to the livestock industries. In spite of its importance, the genetic data and epidemiology of this parasite are not entirely understood. In the present study, the complete S. equinus mitochondrial (mt) genome was determined. The length of S. equinus mt genome DNA sequence is 14,545 bp, containing 36 genes, of which 12 code for protein, 22 for transfer RNA, and two for ribosomal RNA, but lacks atp8 gene. All 36 genes are encoded in the same direction which is consistent with all other Chromadorea nematode mtDNAs published to date. Phylogenetic analysis based on concatenated amino acid sequence data of all 12 protein-coding genes showed that there were two large branches in the Strongyloidea nematodes, and S. equinus is genetically closer to S. vulgaris than to Cylicocyclus insignis in Strongylidae. This new mt genome provides a source of genetic markers for the molecular phylogeny and population genetics of equine strongyles. PMID- 26366672 TI - Double fatal outcome after ruptured vasa previa in monochorionic twins: case report and review of the literature. AB - Vasa previa is a condition in which one or more fetal blood vessels run through the amniotic membranes and cross or run near the external orifice of the uterus. Rupture of membranes can lead to tearing of these vessels and cause acute fetal exsanguination. In monochorionic twin (MC) pregnancies, acute exsanguination in one twin can lead to severe complications in the co-twin due to the presence of inter-twin placental vascular connections. We report a MC pair with severe perinatal asphyxia due to acute exsanguination after prenatally undetected ruptured vasa previa. This resulted in severe hemorrhagic shock in both twins with double fatal outcome. Antenatal detection of vasa previa is of paramount importance to prevent severe morbidity and mortality, especially in MCs. A review of the literature is presented. PMID- 26366674 TI - Early visual processing is enhanced in the midluteal phase of the menstrual cycle. AB - Event-related potential (ERP) studies have revealed an early attentional bias in processing unpleasant emotional images in women. Recent neuroimaging data suggests there are significant differences in cortical emotional processing according to menstrual phase. This study examined the impact of menstrual phase on visual emotional processing in women compared to men. ERPs were recorded from 28 early follicular women, 29 midluteal women, and 27 men while they completed a passive viewing task of neutral and low- and high- arousing pleasant and unpleasant images. There was a significant effect of menstrual phase in early visual processing, as midluteal women displayed significantly greater P1 amplitude at occipital regions to all visual images compared to men. Both midluteal and early follicular women displayed larger N1 amplitudes than men (although this only reached significance for the midluteal group) to the visual images. No sex or menstrual phase differences were apparent in later N2, P3, or LPP. A condition effect demonstrated greater P3 and LPP amplitude to highly arousing unpleasant images relative to all other stimuli conditions. These results indicate that women have greater early automatic visual processing compared to men, and suggests that this effect is particularly strong in women in the midluteal phase at the earliest stage of visual attention processing. Our findings highlight the importance of considering menstrual phase when examining sex differences in the cortical processing of visual stimuli. PMID- 26366673 TI - Current status and future prospects of yellow fever vaccines. AB - Yellow fever 17D vaccine is one of the oldest live-attenuated vaccines in current use that is recognized historically for its immunogenic and safe properties. These unique properties of 17D are presently exploited in rationally designed recombinant vaccines targeting not only flaviviral antigens but also other pathogens of public health concern. Several candidate vaccines based on 17D have advanced to human trials, and a chimeric recombinant Japanese encephalitis vaccine utilizing the 17D backbone has been licensed. The mechanism(s) of attenuation for 17D are poorly understood; however, recent insights from large in silico studies have indicated particular host genetic determinants contributing to the immune response to the vaccine, which presumably influences the considerable durability of protection, now in many cases considered to be lifelong. The very rare occurrence of severe adverse events for 17D is discussed, including a recent fatal case of vaccine-associated viscerotropic disease. PMID- 26366675 TI - Novel techniques for automated seizure registration: Patients' wants and needs. AB - OBJECTIVES: Patient-reported seizure frequency is essential for therapy management and clinical research but lacks validity mainly due to seizure-induced seizure unawareness. Automated seizure detection by mobile monitoring devices promises to settle this serious methodological issue. Here, we explored attitudes and preferences towards future devices for seizure detection in adult patients with therapy-refractory epilepsies. METHODS: A total of 102 inpatients enrolled and underwent a newly constructed semistructured 30-minute interview on automated seizure registration. RESULTS: Most patients would generally apply and permanently use seizure registration devices. Removable devices were preferred (e.g., wristband sensors), but also patch electrodes at invisible body sites appeared acceptable. Only a minority of patients would accept implantations for seizure registration (especially of depth electrodes). Also, permanent optical or acoustical surveillance were accepted by a few patients only. Most patients were ready to care for the device (e.g., charging battery), to have doctor's appointments for device control, and even to pay for the device. Seizure prediction was evaluated as an essential additional function. Only half of the patients wanted emergency calls in case of a seizure. SIGNIFICANCE: Patients would accept automated seizure registration if the device had as little as possible negative effect on daily living. High acceptance might, therefore, be expected for hardware equipment as it is nowadays used by many healthy subjects for physiological self-monitoring and life-logging. The proper medical engineering task of the future, therefore, is to optimize sensors in those highly feasible devices and to establish reliable biomarkers and outcome measures for a diversity of diseases (including epilepsy) from data obtained by this generic hardware. PMID- 26366676 TI - Obstruction increases activation in the right inferior frontal gyrus. AB - The right inferior frontal gyrus (IFG) is involved in intention understanding during interpersonal interactions. To examine how prior experience of cooperation and competition affects one's right IFG activation in the subsequent interaction, using near-infrared spectroscopy (NIRS) we simultaneously measured paired participants' bilateral IFG activations during a turn-taking game. Participant pairs were assigned to either one of two roles: a Builder taking the initial move to copy a target disk-pattern on monitor and the Partner taking the second move to aid in (cooperation) or to obstruct (competition) the Builder. The experiment consisted of two sessions. One participant (B-P) played as a Builder (B-) in session 1 and changed the role to the Partner (-P) in session 2, and vice versa for the paired participant (P-B). NIRS data in competition demonstrated that the Builder (B-) being obstructed in session 1 showed higher right IFG activation when (s)he took a role of obstructor (-P) in session 2 (the obstructed effect), whereas "the cooperated effect" was not revealed in cooperation. These results suggest that prior experience of being obstructed may facilitate understanding of the Builder and/or the obstructor's tactical move, thereby increasing his/her right IFG activation when one is meant to obstruct in subsequent competitions. PMID- 26366678 TI - Glyceraldehyde-3-phosphate dehydrogenase is a mediator of hemocyte-spreading behavior and molecular target of immunosuppressive factor CrV1. AB - Cellular immunity is accompanied by hemocyte-spreading behavior, which undergoes cytoskeletal rearrangement. Polydnaviral factor CpBV-CrV1 can inhibit the hemocyte-spreading behavior and suppress host immune response of Plutella xylostella. However, host target molecule of CpBV-CrV1 that inhibits the hemocyte behavior has not been identified yet. This study used a pull-down approach to identify the target molecule of CpBV-CrV1. A protein bound to CpBV-CrV1 was co precipitated and identified to be glyceraldehyde-3-phosphate dehydrogenase (GAPDH) by LC-MS/MS analysis. RNA interference (RNAi) specific to GAPDH of P. xylostella was found to be able to inhibit the hemocyte-spreading behavior, while RNAi treatments with other glycolytic genes had no effect on the spreading behavior. An addition of recombinant CpBV-CrV1 on hemocyte monolayer interrupted the association between GAPDH and alpha-tubulin in the cytoplasm. Overlay of mutant proteins (Y492A or Y501A with tyrosine to alanine at putative GAPDH binding site) of CpBV-CrV1 on hemocyte monolayer revealed that they could enter hemocytes unlike a mutant in the N-terminal coiled-coil domain. However, they failed to inhibit the hemocyte-spreading behavior without any binding affinity to GAPDH. These results suggest that GAPDH plays a critical role in hemocyte spreading behavior during immune challenge as a molecular target of viral factor CpBV-CrV1. PMID- 26366679 TI - Locally elevated cortisol in lymphoid organs of the developing zebra finch but not Japanese quail or chicken. AB - Glucocorticoids are important for production of functional lymphocytes and immunity. In altricial neonates, adrenal glands are unresponsive and local glucocorticoid synthesis in lymphoid organs may be necessary to support lymphocyte development. Precocial neonates, in contrast, have fully responsive adrenal glucocorticoid production, and lymphoid glucocorticoid synthesis may not be necessary. Here, we found that in altricial zebra finch hatchlings, lymphoid organs had dramatically elevated endogenous glucocorticoid (and precursor) levels compared to levels in circulating blood. Furthermore, while avian adrenals produce corticosterone, finch lymphoid organs had much higher levels of cortisol, an unexpected glucocorticoid in birds. In contrast, precocial Japanese quail and chicken offspring did not have locally elevated lymphoid glucocorticoid levels, nor did their lymphoid organs contain high proportions of cortisol. These results show that lymphoid glucocorticoids differ in identity, concentration, and possibly source, in hatchlings of three different bird species. Locally-regulated glucocorticoids might have species-specific roles in immune development. PMID- 26366677 TI - FANCA safeguards interphase and mitosis during hematopoiesis in vivo. AB - The Fanconi anemia (FA/BRCA) signaling network controls multiple genome housekeeping checkpoints, from interphase DNA repair to mitosis. The in vivo role of abnormal cell division in FA remains unknown. Here, we quantified the origins of genomic instability in FA patients and mice in vivo and ex vivo. We found that both mitotic errors and interphase DNA damage significantly contribute to genomic instability during FA-deficient hematopoiesis and in nonhematopoietic human and murine FA primary cells. Super-resolution microscopy coupled with functional assays revealed that FANCA shuttles to the pericentriolar material to regulate spindle assembly at mitotic entry. Loss of FA signaling rendered cells hypersensitive to spindle chemotherapeutics and allowed escape from the chemotherapy-induced spindle assembly checkpoint. In support of these findings, direct comparison of DNA crosslinking and anti-mitotic chemotherapeutics in primary FANCA-/- cells revealed genomic instability originating through divergent cell cycle checkpoint aberrations. Our data indicate that FA/BRCA signaling functions as an in vivo gatekeeper of genomic integrity throughout interphase and mitosis, which may have implications for future targeted therapies in FA and FA deficient cancers. PMID- 26366680 TI - GPCR Retreat 2014: a good view leads to many discoveries! AB - The GPCR gods smiled on us last year as the 15th Annual GPCR Retreat was held last October 2nd-4th in Bromont, Quebec. The fall colors were at their peak and the meeting attendees were also in fine form. The program was one of the best we have seen at any GPCR-related meeting in years and there was a great deal of excitement about new methodological approaches to understanding receptor biology, new concepts in GPCR signaling and a continued emphasis on translation of these discoveries. This year was also the first year we opened the meeting with a short course on biased agonism and how to measure and analyze it. PMID- 26366681 TI - Temperature Sensitivity of Neural Tube Defects in Zoep Mutants. AB - Neural tube defects (NTD) occur when the flat neural plate epithelium fails to fold into the neural tube, the precursor to the brain and spinal cord. Squint (Sqt/Ndr1), a Nodal ligand, and One-eyed pinhead (Oep), a component of the Nodal receptor, are required for anterior neural tube closure in zebrafish. The NTD in sqt and Zoep mutants are incompletely penetrant. The penetrance of several defects in sqt mutants increases upon heat or cold shock. In this project, undergraduate students tested whether temperature influences the Zoep open neural tube phenotype. Single pairs of adults were spawned at 28.5 degrees C, the normal temperature for zebrafish, and one half of the resulting embryos were moved to 34 degrees C at different developmental time points. Analysis of variance indicated temperature and clutch/genetic background significantly contributed to the penetrance of the open neural tube phenotype. Heat shock affected the embryos only at or before the midblastula stage. Many factors, including temperature changes in the mother, nutrition, and genetic background, contribute to NTD in humans. Thus, sqt and Zoep mutants may serve as valuable models for studying the interactions between genetics and the environment during neurulation. PMID- 26366683 TI - Ventricular Assist Device in Children with Cardiac Graft Failure. AB - We sought to determine whether ventricular assist device (VAD) support is an effective therapy in children with cardiac graft dysfunction. We conducted a retrospective review of VAD usage in this scenario at our institution. Although short-term VAD support was highly successful (89% [eight out of nine] were bridged to recovery), only 29% (2 out of 7) with long-term VAD survived to retransplant. Of note, three out of five mortalities with long-term VAD were related to sepsis (two fungal and one Gram-negative bacterial). Infectious risk imposed by ongoing immunosuppressive therapy limits the role of long-term VAD in this population. PMID- 26366682 TI - Clinical significance of in vivo cytarabine-induced gene expression signature in AML. AB - Despite initial remission, ~60-70% of adult and 30% of pediatric patients experience relapse or refractory AML. Studies so far have identified base line gene expression profiles of pathogenic and prognostic significance in AML; however, the extent of change in gene expression post-initiation of treatment has not been investigated. Exposure of leukemic cells to chemotherapeutic agents such as cytarabine, a mainstay of AML chemotherapy, can trigger adaptive response by influencing leukemic cell transcriptome and, hence, development of resistance or refractory disease. It is, however, challenging to perform such a study due to lack of availability of specimens post-drug treatment. The primary objective of this study was to identify in vivo cytarabine-induced changes in leukemia cell transcriptome and to evaluate their impact on clinical outcome. The results highlight genes relevant to cytarabine resistance and support the concept of targeting cytarabine-induced genes as a means of improving response. PMID- 26366684 TI - Extracorporeal Life Support for Refractory Cardiac Arrest or Shock: A 10-Year Study. AB - We aimed to identify factors associated with hospital mortality among patients receiving extracorporeal life support (ECLS). All consecutive patients treated with ECLS for refractory cardiac arrest or shock in the Caen University Hospital in northwestern France during the last decade were included in a retrospective cohort study. Sixty-four patients were included: 29 with refractory cardiac arrest and 35 with refractory shock. The main reasons for ECLS were acute coronary syndrome (n = 23) and severe poisoning caused by drug intoxication (n = 19). At ECLS initiation, the left ventricular ejection fraction was 16% (+/-11). Initial blood test results were arterial pH = 7.19 (+/-0.20) and plasma lactate = 8.02 (+/-5.88) mmol/L. Forty (63%) patients died including 33 under ECLS. In a multivariate analysis, two factors were independently associated with survival: drug intoxication as the reason for ECLS (adjusted odds ratio [AOR], 0.07; 95% confidence intervals [CI], 0.01-0.28; p < 0.001) and arterial pH (an increase of 0.1 point [AOR, 0.013; 95% CI, <0.001-0.27; p < 0.01]). This study supports early ECLS as a last resort therapeutic option in a highly selected group of patients with refractory cardiac arrest or shock, in particular before profound acidosis occurs and when the cause is reversible. PMID- 26366685 TI - The Quest for Nonthrombotic Surface Modifications to Achieve Hemocompatibility of Implantable Devices. AB - The use of blood-contacting implantable devices is limited by surface-induced thrombosis, which has led to the development of thromboresistant surfaces. Multidisciplinary efforts have promoted the development of surface modifications to minimize thrombosis by targeting surface-induced coagulation. To this date, no material has been identified that remains irrevocably hemocompatible with time but many options are now available with their own limitations. Essential to this review is the understanding of some of the challenges in this field and newer opportunities for hemocompatibility research. This report will also briefly review many of the achievements in the development of hemocompatible biomaterial coating, including surface modifications against protein adsorption and platelet adhesion, biomimetism, and endothelialization. PMID- 26366686 TI - Gastrointestinal Bleeding during Continuous-Flow Left Ventricular Assist Device Support is Associated with Lower Rates of Cardiac Transplantation. AB - Gastrointestinal bleeding (GIB) remains a significant problem after continuous flow left ventricular assist device (CF-LVAD) implantation. We hypothesized that the subsequent need for blood transfusions in patients with GIB may reduce rates of cardiac transplantation. We performed a retrospective review of 232 patients implanted with the HeartMate II (HM II) CF-LVAD from June 2005 through May 2013 at our center to determine risk factors for GIB and assess its effect on cardiac transplantation. Over a total LVAD follow-up time of 364 person-years, 62 GIB episodes occurred in 49 patients (27%), for an event rate of 0.45 gastrointestinal bleeds/patient-year of LVAD support. Women made up 15% of our cohort, yet contributed 29% of the GIB (p = 0.06). Survival at 6 month, 1 year, and 2 years was not statistically different in patients who developed GIB and those who did not (77% vs 78%, 74% vs 71%, and 61% vs 54%, respectively). In transplant-eligible patients, GIB was associated with a 27% lower rate of cardiac transplantation (rate ratio 0.73, p < 0.05). Although the mechanism behind this finding is unclear, GIB appears to be linked to higher transfusion rates, which may cause the development of subsequent allosensitization. PMID- 26366687 TI - Editor's Introduction. PMID- 26366688 TI - Assessment of Liver and Spleen Stiffness in Patients With Myelofibrosis Using FibroScan and Shear Wave Elastography. AB - Liver stiffness and spleen stiffness in patients with myelofibrosis have traditionally been assessed through manual palpation and thus influenced by interobserver variability. In this article, for the first time, liver stiffness and spleen stiffness of patients with myelofibrosis were evaluated through FibroScan and shear wave elastography (SWE). Nine patients with myelofibrosis comprised the study group. They were compared with 11 patients with liver cirrhosis and 8 healthy volunteers. Before the FibroScan study, all patients underwent ultrasound study to delineate the left intercostal space for validated measurements. In patients with myelofibrosis, the mean stiffness of the spleen was 41.3 and 32.9 kilopascals (kPa) through FibroScan and SWE, respectively. The mean stiffness of the liver was 7.8 kPa through FibroScan and 10.4 kPa through SWE. The stiffness of the spleen in patients with cirrhosis was even higher, reaching a mean of 58.5 kPa through FibroScan and 40.5 kPa through SWE. The means were considerably lower among the healthy controls (13.5 and 18.1 kPa, respectively). The correlation between spleen stiffness among the patients with cirrhosis is negative and opposite in direction (r = -0.35) in comparison with the patients with myelofibrosis (r = 0.78). Among the patients with liver cirrhosis and myelofibrosis, spleen size was weakly related to spleen stiffness as assessed through SWE (r = 0.49) but had almost no relation to the FibroScan measure (r = 0.13). The FibroScan and SWE of the spleen have little ability to distinguish between the patients with myelofibrosis and cirrhosis, but they do differentiate both patient groups from the healthy controls. The stiffness of spleen and liver as measured through FibroScan and SWE was not correlated to the longevity of myelofibrosis. PMID- 26366689 TI - Is it Worth to Evaluate the Fetal Heart With Color Doppler Scan at 11 to 13+6 Weeks? AB - This study was conducted to try to achieve the success rate to detect fetal cardiac malformations and/or tricuspid regurgitation with color Doppler during first trimester ultrasound scan within a short period (less than 3 minutes) in a general low-risk population. For this purpose, we started a prospective study, evaluating 240 consecutive single pregnancies, by a single examiner, during the first trimester ultrasound scan (crown to rump length between 45 and 84 mm) using a Voluson E8 system (GE Healthcare, Zipf, Austria) with a 2- to 8-MHz RAB 4-8-D transabdominal probe. Pulsed-wave and color Doppler flow mapping was used to assess the blood flow through the tricuspid valve. In addition, color Doppler was used to evaluate the 4-chamber view, the great vessels ("V sign"), and the right subclavian artery. Blood flow in the tricuspid valve could be examined in 206 cases (85.8%). Of these, tricuspid regurgitation was detected in 17 cases (7.1%) with both pulsed-wave and color Doppler. The 4-chamber view, the V sign, and the right subclavian artery could be evaluated in 188 cases (78.3%). One case of aberrant right subclavian artery and 2 suspicious of cardiac malformations were detected. In our opinion, using color Doppler during first trimester ultrasound scan, even for a short period (<3 minutes), probably adds important information about the fetal heart. PMID- 26366690 TI - Breast Adenomyoepithelioma: Ultrasonography, Elastography, Digital Mammography, Contrast-Enhanced Digital Mammography, and Pathology Findings of This Rare Type of Breast Tumor. AB - Breast adenomyoepithelioma is considered as an uncommon breast tumor. It is evaluated as a variant of intraductal papilloma. The treatment of choice is local resection with free margins. It is the first case of breast adenomyoepithelioma reported with conventional ultrasonography, elastography (both free-hand and acoustic radiation force impulse imaging), digital mammography, contrast-enhanced digital mammography, and pathology findings. A 35-year-old white woman presented with a painless lump of the left breast. Treatment was local resection with free margins. There has been no recurrence for 6 months. Although breast adenomyoepithelioma is an uncommon breast tumor, its awareness is imperative because the differential diagnosis from other breast tumors is quite extensive. PMID- 26366691 TI - Floating Tophi in a Baker Cyst Secondary to Gout: Ultrasound Features and Differential Diagnosis. AB - We report the case of a 36-year-old man with a recent diagnosis of gout, who presents with a fullness behind his right knee that fluctuates in size with time. An ultrasound revealed a Baker cyst that contained both large and punctate internal hyperechoic foci. Cyst aspiration revealed negatively birefringent crystals, which were consistent with gout. PMID- 26366692 TI - Infected Urachal Cyst. PMID- 26366693 TI - Chiari 3 Malformation and Cephalocele: Perinatal Evaluation. PMID- 26366694 TI - Ultrasound Fusion: Role in Interventional Musculoskeletal Radiology. PMID- 26366695 TI - Gestational Trophoblastic Disease and Choriocarcinoma. PMID- 26366696 TI - Classic Mature Cystic Teratoma of the Ovary in a 17-Year-Old Adolescent Girl. PMID- 26366697 TI - Biliary Ascariasis: A Case Report. PMID- 26366701 TI - High-Resolution Ultrasound Characterization of Colonic Lymphoid Hyperplasia in a Case of Active Crohn Colitis. PMID- 26366702 TI - BRAF mutation analysis in circulating free tumor DNA of melanoma patients treated with BRAF inhibitors. AB - BRAFV600E is a unique molecular marker for metastatic melanoma, being the most frequent somatic point mutation in this malignancy. Detection of BRAFV600E in blood could have prognostic and predictive value and could be useful for monitoring response to BRAF-targeted therapy. We developed a rapid, sensitive method for the detection and quantification of BRAFV600E in circulating free DNA (cfDNA) isolated from plasma and serum on the basis of a quantitative 5'-nuclease PCR (Taqman) in the presence of a peptide-nucleic acid. We validated the assay in 92 lung, colon, and melanoma archival serum and plasma samples with paired tumor tissue (40 wild-type and 52 BRAFV600E). The correlation of cfDNA BRAFV600E with clinical parameters was further explored in 22 metastatic melanoma patients treated with BRAF inhibitors. Our assay could detect and quantify BRAFV600E in mixed samples with as little as 0.005% mutant DNA (copy number ratio 1 : 20 000), with a specificity of 100% and a sensitivity of 57.7% in archival serum and plasma samples. In 22 melanoma patients treated with BRAF inhibitors, the median progression-free survival was 3.6 months for those showing BRAFV600E in pretreatment cfDNA compared with 13.4 months for those in whom the mutation was not detected (P=0.021). Moreover, the median overall survival for positive versus negative BRAFV600E tests in pretreatment cfDNA differed significantly (7 vs. 21.8 months, P=0.017). This finding indicates that the sensitive detection and accurate quantification of low-abundance BRAFV600E alleles in cfDNA using our assay can be useful for predicting treatment outcome. PMID- 26366703 TI - Some thoughts on drug interchangeability. AB - Current regulation for generic approval is based on the assessment of average bioequivalence. As indicated by the United States Food and Drug Administration (FDA), an approved generic drug can be used as a substitute for the innovative drug. FDA does not indicate that two generic copies of the same innovative drug can be used interchangeably even though they are bioequivalent to the same brand name drug. In practice, bioequivalence between generic copies of an innovative drug is not required. However, as more generic drug products become available, it is a concern whether the approved generic drug products have the same quality and therapeutic effect as the brand-name drug product and whether they can be used safely and interchangeably. In this article, several criteria including a newly proposed criterion for assessing drug interchangeability are studied. In addition, comments on possible study designs and power calculation for sample size under a specific design are also discussed. PMID- 26366704 TI - Intestinal Intramural Vascular Anastomoses. AB - INTRODUCTION: Present surgical techniques are rarely relying on intestinal intramural vascular anastomoses; however, this could open new limits in reconstructive surgery. Our aim was to study the efficacy of the antimesenteric and the longitudinal intramural vascular anastomoses in a porcine model. MATERIAL AND METHODS: Five minipigs were used. Antimesenteric anastomoses: jejunal loops were detubularized by cutting along the antimesenteric line (Control), in the middle between the mesenteric and antimesenteric border (Group 1) and close to the mesenteric line (Group 2). Mucosal microcirculation (red blood cell velocity, perfusion rate) was recorded with orthogonal polarization spectral imaging (Cytoscan A/R) at the long edge of the detubularized bowel. Longitudinal anastomoses: records were made on a continuous jejunal loop following antimesenteric incision, detubularization, and subsequent ligation of 2, 4, and 6 neighboring vasa recta in the middle of the loop. The same study was repeated on the free end of completely divided jejunal segments with ligation of 2, 4, or 6 vasa recta. RESULTS: Antimesenteric anastomoses: There was no statistically significant difference in red blood cell velocity and perfusion rate between Control and Groups 1 and 2. Longitudinal anastomoses: The red blood cell velocity dropped significantly, while the perfusion rate did not change significantly after ligation of 4 vasa recta in the continuous loop. In the loop with a free end, however, both parameters decreased significantly after ligation of four vessels. CONCLUSION: It is safe to rely on antimesenteric intramural anastomoses but strong limitation of longitudinal intramural vascular anastomoses should be considered in intestinal reconstructions. PMID- 26366705 TI - The IL-12/23/STAT Axis as a Therapeutic Target in Inflammatory Bowel Disease: Mechanisms and Evidence in Man. AB - BACKGROUND: In inflamed tissues of patients with inflammatory bowel disease (IBD), many immune and non-immune cells produce a vast array of cytokines, which contribute to expand and maintain the pathologic process. Key Message: Interleukin (IL)-12 and IL-23, 2 heterodimeric cytokines sharing the common p40 subunit, are over-produced in IBD and supposed to play a major role in promoting and/or sustaining the pro-inflammatory cytokine response in these disorders. IL 12 targets mostly T cells and innate lymphoid cells and through activation of Stat4 promotes T helper (Th)1 cell polarization, interferon-x03B3; and IL-21 production, while IL-23 activates Stat3 thus amplifying Th17 cell programs. These observations together with the demonstration that IL-12 and IL-23 drive pathogenic responses in animal models of colitis have paved the way for the development of IL-12p40 blockers. Two monoclonal antibodies (ustekinumab and briakinumab) targeting p40 have been tested in Crohn's disease (CD) patients. Blockade of IL-12p40 is beneficial in CD patients resistant to tumor necrosis factor (TNF) antagonists and promotes resolution of psoriatic lesions that develop in IBD patients following anti-TNF therapy. CONCLUSIONS: The available human data support the pathogenic role of IL-12/IL-23 in IBD and suggest that IL 12p40 blockers could help manage some subsets of IBD patients. PMID- 26366706 TI - Vestibular Prostheses Investigated in Animal Models. AB - Loss of peripheral vestibular function results in debilitating postural, perceptual, and visual symptoms. A new approach to treating this clinical problem is to replace some aspects of peripheral vestibular function with a prosthesis that senses head motion and provides this information to the brain by stimulating the vestibular nerve. In this paper, I review studies done in animals over the past 15 years which lay the groundwork for transferring this approach to human patients with severe peripheral vestibular damage. The animal studies demonstrate that the visual and perceptual defects associated with peripheral vestibular damage can be improved with a vestibular implant, but the data on postural control remain less conclusive at this point in time. PMID- 26366707 TI - Bowel Ultrasonography in Inflammatory Bowel Disease. AB - BACKGROUND: The diagnosis of inflammatory bowel disease (IBD) is based on a combination of endoscopic, clinical and biochemical investigations as well as cross-sectional imaging. The applications of cross-sectional imaging in IBD are manifold. Ultrasonography has emerged as an important imaging modality in the diagnosis of Crohn's disease (CD) as well as for monitoring disease progression and in the therapeutic response to CD and ulcerative colitis (UC). Key Messages: Ultrasonography is non-invasive, radiation free, cheap, easy to use and well tolerated and accepted by patients. Bowel ultrasonography can be used for the primary diagnosis of CD as it has a similar sensitivity and specificity like that of MRI and CT, particularly in the case of CD. Ultrasonography can also be used to monitor treatment response to therapy and to detect disease recurrence of CD as well as UC. In CD, ultrasonography can also be used to detect complications such as strictures as well as extramural complications, including abscesses and fistulas. Contrast-enhanced ultrasonography is a useful tool that might be helpful to detect certain indications in CD, in particular the differentiation between abscesses and inflammation. CONCLUSION: A variety of advantages of bowel ultrasonography over other imaging modalities suggest the more frequent use of this method to manage IBD patients in daily practice. Bowel ultrasonography should be a standard tool in IBD centers. PMID- 26366708 TI - Understanding the association between diet and nutrition in upper gastrointestinal cancer. AB - Human vulnerability to cancers of the upper gastrointestinal tract is strongly influenced by environmental factors. The esophagus, in particular, is highly vulnerable to the combined effects of exposure to environmental carcinogens and malnutrition, particularly in certain extreme environments of the developing world. Even in high-income countries, dietary carcinogens and nutrition play a major role in the etiology of oropharyngeal, esophageal and, to a lesser extent, gastric cancers, but the mechanisms are poorly understood. A thorough understanding of the biological mechanisms underlying the vulnerability of these organs to neoplasia would shed further light on the etiology of upper gastrointestinal cancers in all environments. In the meantime, the epidemiological evidence suggests that the risks can be minimized by dietary patterns that adhere closely to current public health recommendations, coupled with maintenance of body mass index within the healthy range. PMID- 26366709 TI - Phytoremediation potential of some agricultural plants on heavy metal contaminated mine waste soils, salem district, tamilnadu. AB - The Pot culture experiment performed for phytoextraction potential of selected agricultural plants [millet (Eleusine coracana), mustard (Brassica juncea), jowar (Sorghum bicolor), black gram (Vigna mungo), pumpkin (Telfairia occidentalis)] grown in metal contaminated soils around the Salem region, Tamilnadu, India. Physiochemical characterization of soils, reported as low to medium level of N, P, K was found in test soils. The Cr content higher in mine soils than control and the values are 0.176 mg/L in Dalmia soil and 0.049 mg/L in Burn & Co soil. The germination rate low in mine soil than control soils (25 to 85%). The content of chlorophyll, carotenoid, carbohydrate and protein decreased in mine soils than control. The morphological parameters and biomass values decreased in experimental plants due to metal accumulation. Proline content increased in test plants and ranged from 0.113 mg g(-1) to 0.858 mg g(-1) which indicate the stress condition due to toxicity of metals. Sorghum and black gram plants reported as metal tolerant capacity. Among the plants, Sorghum produced good results (both biomass and biochemical parameters) which equal to control plant and suggests Sorghum plant is an ideal for remediation of metal contaminated soils. PMID- 26366710 TI - The histone lysine methyltransferase KMT2D sustains a gene expression program that represses B cell lymphoma development. AB - The gene encoding the lysine-specific histone methyltransferase KMT2D has emerged as one of the most frequently mutated genes in follicular lymphoma and diffuse large B cell lymphoma; however, the biological consequences of KMT2D mutations on lymphoma development are not known. Here we show that KMT2D functions as a bona fide tumor suppressor and that its genetic ablation in B cells promotes lymphoma development in mice. KMT2D deficiency also delays germinal center involution and impedes B cell differentiation and class switch recombination. Integrative genomic analyses indicate that KMT2D affects methylation of lysine 4 on histone H3 (H3K4) and expression of a set of genes, including those in the CD40, JAK STAT, Toll-like receptor and B cell receptor signaling pathways. Notably, other KMT2D target genes include frequently mutated tumor suppressor genes such as TNFAIP3, SOCS3 and TNFRSF14. Therefore, KMT2D mutations may promote malignant outgrowth by perturbing the expression of tumor suppressor genes that control B cell-activating pathways. PMID- 26366711 TI - Early life dynamics of the human gut virome and bacterial microbiome in infants. AB - The early years of life are important for immune development and influence health in adulthood. Although it has been established that the gut bacterial microbiome is rapidly acquired after birth, less is known about the viral microbiome (or 'virome'), consisting of bacteriophages and eukaryotic RNA and DNA viruses, during the first years of life. Here, we characterized the gut virome and bacterial microbiome in a longitudinal cohort of healthy infant twins. The virome and bacterial microbiome were more similar between co-twins than between unrelated infants. From birth to 2 years of age, the eukaryotic virome and the bacterial microbiome expanded, but this was accompanied by a contraction of and shift in the bacteriophage virome composition. The bacteriophage-bacteria relationship begins from birth with a high predator-low prey dynamic, consistent with the Lotka-Volterra prey model. Thus, in contrast to the stable microbiome observed in adults, the infant microbiome is highly dynamic and associated with early life changes in the composition of bacteria, viruses and bacteriophages with age. PMID- 26366712 TI - Disruption of KMT2D perturbs germinal center B cell development and promotes lymphomagenesis. AB - Mutations in the gene encoding the KMT2D (or MLL2) methyltransferase are highly recurrent and occur early during tumorigenesis in diffuse large B cell lymphoma (DLBCL) and follicular lymphoma (FL). However, the functional consequences of these mutations and their role in lymphomagenesis are unknown. Here we show that FL- and DLBCL-associated KMT2D mutations impair KMT2D enzymatic activity, leading to diminished global H3K4 methylation in germinal-center (GC) B cells and DLBCL cells. Conditional deletion of Kmt2d early during B cell development, but not after initiation of the GC reaction, results in an increase in GC B cells and enhances B cell proliferation in mice. Moreover, genetic ablation of Kmt2d in mice overexpressing Bcl2 increases the incidence of GC-derived lymphomas resembling human tumors. These findings suggest that KMT2D acts as a tumor suppressor gene whose early loss facilitates lymphomagenesis by remodeling the epigenetic landscape of the cancer precursor cells. Eradication of KMT2D deficient cells may thus represent a rational therapeutic approach for targeting early tumorigenic events. PMID- 26366713 TI - Controlled Complete Suppression of Single-Atom Inelastic Spin and Orbital Cotunneling. AB - The inelastic portion of the tunnel current through an individual magnetic atom grants unique access to read out and change the atom's spin state, but it also provides a path for spontaneous relaxation and decoherence. Controlled closure of the inelastic channel would allow for the latter to be switched off at will, paving the way to coherent spin manipulation in single atoms. Here, we demonstrate complete closure of the inelastic channels for both spin and orbital transitions due to a controlled geometric modification of the atom's environment, using scanning tunneling microscopy (STM). The observed suppression of the excitation signal, which occurs for Co atoms assembled into chains on a Cu2N substrate, indicates a structural transition affecting the dz(2) orbital, effectively cutting off the STM tip from the spin-flip cotunneling path. PMID- 26366715 TI - Highly asymmetrical glycerol diether bolalipids: synthesis and temperature dependent aggregation behavior. AB - In the present work, we describe the synthesis and temperature-dependent aggregation behavior of two examples of a new class of highly asymmetrical glycerol diether bolaphospholipids. The bolalipids contain a long alkyl chain (C32) bound to glycerol in the sn-3 position, carrying a hydroxyl group at the omega position. The C16 alkyl chain in the sn-2 position either possesses a racemic methyl branch at the 10 position of the short alkyl chain (lipid II) or does not (lipid I). The sn-1 position of the glycerol is linked to a zwitterionic phosphocholine moiety. The temperature-dependent aggregation behavior of both bolalipids was studied using differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy, and X-ray scattering. Aggregate structures were visualized by transmission electron microscopy (TEM). We show that both bolalipids self-assemble into large lamellar sheetlike aggregates. Closed lipid vesicles or other aggregate structures such as tubes or nanofibers, as usually found for diglycerol tetraether lipids, were not observed. Within the lamellae the bolalipid molecules are arranged in an antiparallel (interdigitated) orientation. Lipid I, without an additional methyl moiety in the short alkyl chain, shows a lamellar phase with high crystallinity up to a temperature of 34 degrees C, which was not observed before for other phospholipids. PMID- 26366714 TI - Vitamin D Status and Rates of Cognitive Decline in a Multiethnic Cohort of Older Adults. AB - IMPORTANCE: Vitamin D (VitD) deficiency is associated with brain structural abnormalities, cognitive decline, and incident dementia. OBJECTIVE: To assess associations between VitD status and trajectories of change in subdomains of cognitive function in a cohort of ethnically diverse older adults. DESIGN, SETTING, AND PARTICIPANTS: Longitudinal multiethnic cohort study of 382 participants in an outpatient clinic enrolled between February 2002 and August 2010 with baseline assessment and yearly follow-up visits. Serum 25 hydroxyvitamin D (25-OHD) was measured, with VitD status defined as the following: deficient, less than 12 ng/mL (to convert to nanomoles per liter, multiply by 2.496); insufficient, 12 to less than 20 ng/mL; adequate, 20 to less than 50 ng/mL; or high, 50 ng/mL or higher. Subdomains of cognitive function were assessed using the Spanish and English Neuropsychological Assessment Scales. Associations were evaluated between 25-OHD levels (as continuous and categorical [deficient, insufficient, or adequate]) and trajectories of cognitive decline. MAIN OUTCOMES AND MEASURES: Serum 25-OHD levels, cognitive function, and associations between 25-OHD levels and trajectories of cognitive decline. RESULTS: Participants (N = 382 at baseline) had a mean (SD) age of 75.5 (7.0) years; 61.8% were women; and 41.4% were white, 29.6% African American, 25.1% Hispanic, and 3.9% other race/ethnicity. Diagnosis at enrollment included 17.5% with dementia, 32.7% with mild cognitive impairment, and 49.5% cognitively normal. The mean (SD) 25-OHD level was 19.2 (11.7) ng/mL, with 26.2% of participants being VitD deficient and 35.1% insufficient. The mean (SD) 25-OHD levels were significantly lower for African American and Hispanic participants compared with white participants (17.9 [15.8] and 17.2 [8.4] vs 21.7 [10.0] ng/mL, respectively; P < .001 for both). The mean (SD) 25-OHD levels were similarly lower in the dementia group compared with the mild cognitive impairment and cognitively normal groups (16.2 [9.4] vs 20.0 [10.3] and 19.7 [13.1] ng/mL, respectively; P = .006). The mean (SD) follow-up was 4.8 (2.5) years. Rates of decline in episodic memory and executive function among VitD-deficient (episodic memory: beta = -0.04 [SE = 0.02], P = .049; executive function: beta = -0.05 [SE = 0.02], P = .01) and VitD-insufficient (episodic memory: beta = -0.06 [SE = 0.02], P < .001; executive function: beta = -0.04 [SE = 0.02], P = .008) participants were greater than those with adequate status after controlling for age, sex, education, ethnicity, body mass index, season of blood draw, vascular risk, and apolipoprotein E4 genotype. Vitamin D status was not significantly associated with decline in semantic memory or visuospatial ability. Exclusion of participants with dementia did not substantially affect the associations between VitD status and rates of cognitive decline. CONCLUSIONS AND RELEVANCE: Low VitD status was associated with accelerated decline in cognitive function domains in ethnically diverse older adults, including African American and Hispanic individuals who exhibited a high prevalence of VitD insufficiency or deficiency. It remains to be determined whether VitD supplementation slows cognitive decline. PMID- 26366717 TI - Chelate cooperativity effects on the formation of di- and trivalent pseudo[2]rotaxanes with diketopiperazine threads and tetralactam wheels. AB - The formation of singly, doubly and triply threaded pseudo[2]rotaxanes with diketopiperazine threads and tetralactam wheels is investigated with respect to chelate cooperativity effects on multivalent binding. Two series of guest molecules are prepared which differ with respect to their spacers, one with preorganised centrepieces with di- or tripodal roof-like structures, one with more flexible spacers. The thermodynamics of pseudorotaxane formation is examined using isothermal titration calorimetry and (1)H NMR spectroscopy. Force-field calculations provide more detailed structural insight and help rationalizing the thermodynamic data. All di- and trivalent pseudorotaxanes exhibit positive chelate cooperativity presumably arising from spacer-spacer interactions. Higher cooperativity factors are observed for the more preorganised threads. PMID- 26366716 TI - Exploring the relationship between eating disorder symptoms and substance use severity in women with comorbid PTSD and substance use disorders. AB - BACKGROUND: Eating disorders (ED) and substance use disorders (SUD) commonly co occur, especially in conjunction with posttraumatic stress disorder (PTSD), yet little is known about ED and ED symptoms in women presenting to addiction treatment programs. OBJECTIVE: We examined the association between ED symptoms and substance use frequency and severity in a sample of women with a DSM IV diagnosis of current SUD and PTSD enrolled in SUD treatment. METHOD: Participants were 122 women from four substance abuse treatment sites who participated in a multi-site clinical trial through the National Institute of Drug Abuse Clinical Trials Network (NIDA CTN). The Eating Disorder Examination-Questionnaire (EDE-Q), the Clinician's Administered PTSD Scale (CAPS) and the Addiction Severity Index (ASI) were administered at baseline and correlational analyses were performed. Variables that significantly correlated with EDE-Q total and subscale scores were entered into a linear regression analysis. RESULTS: Scores on the EDE-Q Global scale, as well as the Eating Concern, Weight Concern and Shape Concern subscales of the EDE-Q were significantly associated with Caucasian race/ethnicity, past 30 day opiate use, higher ASI Psychiatric Subscale score and lower ASI Employment Subscale score. CONCLUSION: Although exploratory, these findings suggest that there may be a relationship between addiction severity, use of certain drugs of abuse and eating disorder symptoms, particularly those involving weight and shape concerns in women with comorbid PTSD and SUD. PMID- 26366718 TI - Volume phase transition mechanism of poly[oligo(ethylene glycol)methacrylate] based thermo-responsive microgels with poly(ionic liquid) cross-linkers. AB - Thermo-dynamic volume phase transition mechanisms of poly[oligo(ethylene glycol)methacrylate] (POEGMA) based microgels with poly(ionic liquid) (PIL) cross linking moieties are investigated in detail on the basis of temperature-dependent Fourier transform infrared (FTIR) spectroscopy. The original FTIR data are further analysed by two-dimensional correlation spectroscopy (2Dcos) with the perturbation correlation moving window (PCMW) technique. It is observed that the content of hydrophilic PIL cross-linking structure strongly affects the temperature induced volume phase transition mechanism of microgels in which the less cross-linked microgel exhibits a sharp volume phase transition process while the highly cross-linked microgel presents a broad transition behavior. Peculiarly, the dehydration of C-H groups acts as the driving force for the whole phase transition process within the less cross-linked microgel network and cooperative response of chemical groups is identified. It is deduced that the hydrophilic PIL moieties develop polymer-water-polymer interactions with C=O groups as C=O...D2O-PIL hydrogen bonds emerge in the less cross-linked system. As regards the highly cross-linked microgel system, the phase transition process is driven by the disruption of hydrogen bonds between C=O groups and water molecules while the response of C-H groups becomes insensitive. PIL moieties passively dehydrate following the dehydration of C-H groups on oligo(ethylene glycol) side chains and no hydrogen bond between C=O group and IL-D2O association appears during the phase transition process. PMID- 26366719 TI - The Association Between Behavior Restrictions in Doing-the-Month Practice and Mental Health Status Among Postpartum Women. AB - OBJECTIVES: Doing-the-month practice has been commonly observed by women during the first month after delivery for hundreds of years in several countries of Asia. This retrospective study examined the correlation between these restricted behaviors and mental status in postpartum women. MATERIALS AND METHODS: The frequencies of seven restricted behaviors during the first month after delivery and levels of depression, anxiety, and sleep quality were measured in 341 women 4 6 weeks after delivery through self-reported questionnaires. The multivariate linear regression model was used to determine independent behavioral predictors for depression, anxiety, and sleep quality. RESULTS: Bathing or showering was an independent predictor of low depression status, low anxiety status (p<0.05), and good sleep quality (p<0.001). Behaviors related to high depression status were touching cold water and squatting (both p<0.05). Squatting was also related to high anxiety status (p<0.01), while exposing oneself to drafts was related to poor sleep quality (p<0.05). CONCLUSION: The results indicate that the restrictions on squatting, touching cold water, and exposure to drafts are positively associated with good mental health in postpartum women and are worth preserving; however, the restriction on bathing or showering might negatively impact the mental health of postpartum women and needs further evaluation. PMID- 26366720 TI - Pollinosis and all-cause mortality among middle-aged and elderly Japanese: a population-based cohort study. AB - BACKGROUND: Having an allergic disease may have health implications beyond those more commonly associated with allergy given that previous epidemiological studies have suggested that both atopy and allergy are linked to mortality. More viable immune functioning among the elderly, as indicated by the presence of an allergic disease, might therefore be associated with differences in all-cause mortality. OBJECTIVE: Using data from a Japanese cohort, this study examined whether having pollinosis (a form of allergic rhinitis) in a follow-up survey could predict all cause and cause-specific mortality. METHODS: Data came from the Komo-Ise cohort, which at its 1993 baseline recruited residents aged 40-69 years from two areas in Gunma prefecture, Japan. The current study used information on pollinosis that was obtained from the follow-up survey in 2000. Mortality and migration data were obtained throughout the follow-up period up to December 2008. Proportional hazard models were used to examine the relation between pollinosis and mortality. RESULTS: At the 2000 follow-up survey, 12% (1088 of 8796) of respondents reported that they had pollinosis symptoms in the past 12 months. During the 76 186 person years of follow-up, 748 died from all causes. Among these, there were 37 external, 208 cardiovascular, 74 respiratory, and 329 neoplasm deaths. After adjusting for potential confounders, pollinosis was associated with significantly lower all-cause [hazard ratio 0.57 (95% confidence interval = 0.38-0.87)] and neoplasms mortality [hazard ratio 0.48 (95% confidence interval = 0.26-0.92)]. CONCLUSIONS AND CLINICAL RELEVANCE: Having an allergic disease (pollinosis) at an older age may be indicative of more viable immune functioning and be protective against certain causes of death. Further research is needed to determine the possible mechanisms underlying the association between pollinosis and mortality. PMID- 26366721 TI - Common MIR146A Polymorphisms in Chinese Ankylosing Spondylitis Subjects and Controls. AB - Common polymorphisms of microRNA gene MIR146A were reported as associated with different autoimmune diseases, include systemic lupus erythematosus, psoriatic arthritis, asthma and ankylosing spondylitis. In this study we investigated MIR146A SNPs in Chinese people with ankylosing spondylitis. Three common SNPs: rs2910164, rs2431697 and rs57095329 were selected and genotyped in 611 patients and 617 controls. We found no association between these SNPs and ankylosing spondylitis in our samples. PMID- 26366722 TI - Sodium-dependent vitamin C transporter-2 mediates vitamin C transport at the cortical nerve terminal. AB - It has been shown that vitamin C (VC) is transported at synaptic boutons, but how this occurs has not been elucidated. This study investigates the role of the sodium-dependent vitamin C transporter-2 (SVCT2) in transporting VC at the cortical nerve terminal. Immunostaining of cultured mouse superior cervical ganglion cells showed the SVCT2 to be expressed in presynaptic boutons, colocalizing with the vesicular monoamine transporter-2 and the norepinephrine transporter. Immunoblotting of enriched cortical synaptosomes demonstrated that the SVCT2 was enriched in presynaptic fractions, confirming a predominantly presynaptic location. In crude synaptosomes, known inhibitors of SVCT2 inhibited uptake of VC. Furthermore, the kinetic features of VC uptake were consistent with SVCT2-mediated function. VC was also found to efflux from synaptosomes by a mechanism not involving the SVCT2. Indeed, VC efflux was substantially offset by reuptake of VC on the SVCT2. The presence and function of the SVCT2 at the presynaptic nerve terminal suggest that it is the transporter responsible for recovery of VC released into the synaptic cleft. PMID- 26366724 TI - Correction: Using Dynamic Multi-Task Non-Negative Matrix Factorization to Detect the Evolution of User Preferences in Collaborative Filtering. PMID- 26366723 TI - Impact of Diet-Induced Obesity and Testosterone Deficiency on the Cardiovascular System: A Novel Rodent Model Representative of Males with Testosterone-Deficient Metabolic Syndrome (TDMetS). AB - INTRODUCTION: Current models of obesity utilise normogonadic animals and neglect the strong relationships between obesity-associated metabolic syndrome (MetS) and male testosterone deficiency (TD). The joint presentation of these conditions has complex implications for the cardiovascular system that are not well understood. We have characterised and investigated three models in male rats: one of diet induced obesity with the MetS; a second using orchiectomised rats mimicking TD; and a third combining MetS with TD which we propose is representative of males with testosterone deficiency and the metabolic syndrome (TDMetS). METHODS: Male Wistar rats (n = 24) were randomly assigned to two groups and provided ad libitum access to normal rat chow (CTRL) or a high fat/high sugar/low protein "obesogenic" diet (OGD) for 28 weeks (n = 12/group). These groups were further sub-divided into sham-operated or orchiectomised (ORX) animals to mimic hypogonadism, with and without diet-induced obesity (n = 6/group). Serum lipids, glucose, insulin and sex hormone concentrations were determined. Body composition, cardiovascular structure and function; and myocardial tolerance to ischemia-reperfusion were assessed. RESULTS: OGD-fed animals had 72% greater fat mass; 2.4-fold greater serum cholesterol; 2.3-fold greater serum triglycerides and 3-fold greater fasting glucose (indicative of diabetes mellitus) compared to CTRLs (all p<0.05). The ORX animals had reduced serum testosterone and left ventricle mass (p<0.05). In addition to the combined differences observed in each of the isolated models, the OGD, ORX and OGD+ORX models each had greater CK-MB levels following in vivo cardiac ischemia-reperfusion insult compared to CTRLs (p<0.05). CONCLUSION: Our findings provide evidence to support that the MetS and TD independently impair myocardial tolerance to ischemia-reperfusion. The combined OGD+ORX phenotype described in this study is a novel animal model with associated cardiovascular risk factors and complex myocardial pathology which may be representative of male patients presenting with TDMetS. PMID- 26366725 TI - Surfactant Protein D Binds to Coxiella burnetii and Results in a Decrease in Interactions with Murine Alveolar Macrophages. AB - Coxiella burnetii is a Gram-negative, obligate intracellular bacterium and the causative agent of Q fever. Infections are usually acquired after inhalation of contaminated particles, where C. burnetii infects its cellular target cells, alveolar macrophages. Respiratory pathogens encounter the C-type lectin surfactant protein D (SP-D) during the course of natural infection. SP-D is a component of the innate immune response in the lungs and other mucosal surfaces. Many Gram-negative pulmonary pathogens interact with SP-D, which can cause aggregation, bactericidal effects and aid in bacterial clearance. Here we show that SP-D binds to C. burnetii in a calcium-dependent manner with no detectable bacterial aggregation or bactericidal effects. Since SP-D interactions with bacteria often alter macrophage interactions, it was determined that SP-D treatment resulted in a significant decrease in C. burnetii interactions to a mouse alveolar macrophage model cell line MH-S indicating SP-D causes a significant decrease in phagocytosis. The ability of SP-D to modulate macrophage activation by C. burnetii was tested and it was determined that SP-D does not alter the correlates measured for macrophage activation. Taken together these studies support those demonstrating limited activation of alveolar macrophages with C. burnetii and demonstrate interactions with SP-D participate in reduction of phagocyte attachment and phagocytosis. PMID- 26366728 TI - Movement Behaviour of Traditionally Managed Cattle in the Eastern Province of Zambia Captured Using Two-Dimensional Motion Sensors. AB - Two-dimensional motion sensors use electronic accelerometers to record the lying, standing and walking activity of cattle. Movement behaviour data collected automatically using these sensors over prolonged periods of time could be of use to stakeholders making management and disease control decisions in rural sub Saharan Africa leading to potential improvements in animal health and production. Motion sensors were used in this study with the aim of monitoring and quantifying the movement behaviour of traditionally managed Angoni cattle in Petauke District in the Eastern Province of Zambia. This study was designed to assess whether motion sensors were suitable for use on traditionally managed cattle in two veterinary camps in Petauke District in the Eastern Province of Zambia. In each veterinary camp, twenty cattle were selected for study. Each animal had a motion sensor placed on its hind leg to continuously measure and record its movement behaviour over a two week period. Analysing the sensor data using principal components analysis (PCA) revealed that the majority of variability in behaviour among studied cattle could be attributed to their behaviour at night and in the morning. The behaviour at night was markedly different between veterinary camps; while differences in the morning appeared to reflect varying behaviour across all animals. The study results validate the use of such motion sensors in the chosen setting and highlight the importance of appropriate data summarisation techniques to adequately describe and compare animal movement behaviours if association to other factors, such as location, breed or health status are to be assessed. PMID- 26366726 TI - Overexpression of EcbHLH57 Transcription Factor from Eleusine coracana L. in Tobacco Confers Tolerance to Salt, Oxidative and Drought Stress. AB - Basic helix-loop-helix (bHLH) transcription factors constitute one of the largest families in plants and are known to be involved in various developmental processes and stress tolerance. We report the characterization of a stress responsive bHLH transcription factor from stress adapted species finger millet which is homologous to OsbHLH57 and designated as EcbHLH57. The full length sequence of EcbHLH57 consisted of 256 amino acids with a conserved bHLH domain followed by leucine repeats. In finger millet, EcbHLH57 transcripts were induced by ABA, NaCl, PEG, methyl viologen (MV) treatments and drought stress. Overexpression of EcbHLH57 in tobacco significantly increased the tolerance to salinity and drought stress with improved root growth. Transgenic plants showed higher photosynthetic rate and stomatal conductance under drought stress that resulted in higher biomass. Under long-term salinity stress, the transgenic plants accumulated higher seed weight/pod and pod number. The transgenic plants were also tolerant to oxidative stress and showed less accumulation of H202 and MDA levels. The overexpression of EcbHLH57 enhanced the expression of stress responsive genes such as LEA14, rd29A, rd29B, SOD, APX, ADH1, HSP70 and also PP2C and hence improved tolerance to diverse stresses. PMID- 26366727 TI - Nicotinic Acid Accelerates HDL Cholesteryl Ester Turnover in Obese Insulin Resistant Dogs. AB - AIM: Nicotinic acid (NA) treatment decreases plasma triglycerides and increases HDL cholesterol, but the mechanisms involved in these change are not fully understood. A reduction in cholesteryl ester transfer protein (CETP) activity has been advanced to explain most lipid-modulating effects of NA. However, due to the central role of CETP in reverse cholesterol transport in humans, other effects of NA may have been hidden. As dogs have no CETP activity, we conducted this study to examine the specific effects of extended-release niacin (NA) on lipids and high-density lipoprotein (HDL) cholesteryl ester (CE) turnover in obese Insulin Resistant dogs with increase plasma triglycerides. METHODS: HDL kinetics were assessed in fasting dogs before and four weeks after NA treatment through endogenous labeling of cholesterol and apolipoprotein AI by simultaneous infusion of [1,2 13C2] acetate and [5,5,5 2H3] leucine for 8 h. Kinetic data were analyzed by compartmental modeling. In vitro cell cholesterol efflux of serum from NA treated dogs was also measured. RESULTS: NA reduced plasma total cholesterol, low density lipoprotein cholesterol, HDL cholesterol, triglycerides (TG), and very low-density lipoprotein TG concentrations (p < 0.05). The kinetic study also showed a higher cholesterol esterification rate (p < 0.05). HDL-CE turnover was accelerated (p < 0.05) via HDL removal through endocytosis and selective CE uptake (p < 0.05). We measured an elevated in vitro cell cholesterol efflux (p < 0.05) with NA treatment in accordance with a higher cholesterol esterification. CONCLUSION: NA decreased HDL cholesterol but promoted cholesterol efflux and esterification, leading to improved reverse cholesterol transport. These results highlight the CETP-independent effects of NA in changes of plasma lipid profile. PMID- 26366729 TI - Cross Protection against Influenza A Virus by Yeast-Expressed Heterologous Tandem Repeat M2 Extracellular Proteins. AB - The influenza M2 ectodomain (M2e) is well conserved across human influenza A subtypes, but there are few residue changes among avian and swine origin influenza A viruses. We expressed a tandem repeat construct of heterologous M2e sequences (M2e5x) derived from human, swine, and avian origin influenza A viruses using the yeast expression system. Intramuscular immunization of mice with AS04 adjuvanted M2e5x protein vaccines was effective in inducing M2e-specific antibodies reactive to M2e peptide and native M2 proteins on the infected cells with human, swine, or avian influenza virus, mucosal and systemic memory cellular immune responses, and cross-protection against H3N2 virus. Importantly, M2e5x immune sera were found to confer protection against different subtypes of H1N1 and H5N1 influenza A viruses in naive mice. Also, M2e5x-immune complexes of virus infected cells stimulated macrophages to secrete cytokines via Fc receptors, indicating a possible mechanism of protection. The present study provides evidence that M2e5x proteins produced in yeast cells could be developed as a potential universal influenza vaccine. PMID- 26366730 TI - Cytokine Response after Stimulation with Key Commensal Bacteria Differ in Post Infectious Irritable Bowel Syndrome (PI-IBS) Patients Compared to Healthy Controls. AB - BACKGROUND: Microbial dysbiosis and prolonged immune activation resulting in low grade inflammation and intestinal barrier dysfunction have been suggested to be underlying causes of post-infectious irritable bowel syndrome (PI-IBS). The aim of this study was to evaluate the difference in cytokine response between mucosal specimens of PI-IBS patients and healthy controls (HC) after ex vivo stimulation with key anaerobic bacteria. METHODS: Colonic biopsies from 11 PI-IBS patients and 10 HC were stimulated ex vivo with the commensal bacteria Bacteroides ovatus, Ruminococcus gnavus, Akkermansia muciniphila, Subdoligranulum variabile and Eubacterium limosum, respectively. The cytokine release (IL-1beta, IL-2, IL-8, IL 10, IL-13, IL-17, TNF-alpha and IFN-gamma) in stimulation supernatants was analyzed using the LUMINEX assay. Comparison of cytokine release between PI-IBS patients and healthy controls was performed taking both unstimulated and bacterially stimulated mucosal specimens into account. KEY RESULTS: IL-13 release from mucosal specimens without bacterial stimulation was significantly lower in PI-IBS patients compared to HC (p < 0.05). After stimulation with Subdoligranulum variabile, IL-1beta release from PI-IBS patients was significantly increased compared to HC (p < 0.05). Stimulation with Eubacterium limosum resulted in a significantly decreased IL-10 release in HC compared to PI-IBS patients (p < 0.05) and a tendency to decreased IL-13 release in HC compared to PI-IBS patients (p = 0.07). CONCLUSIONS & INFERENCES: PI-IBS patients differ from HC with regard to cytokine release ex vivo after stimulation with selected commensal bacteria. Hence, our results support that the pathogenesis of PI-IBS comprises an altered immune response against commensal gut microbes. PMID- 26366731 TI - Investigation on Crude and High-Temperature Heated Coffee Oil by ATR-FTIR Spectroscopy along with Antioxidant and Antimicrobial Properties. AB - The coffee oil has a promising potential to be used in food industry, but an efficient use, especially in products that required high-temperature heating, depends on its chemical composition and the changes induced by processing. Since there is little information on this topic, the aim of our study was to investigate the crude green and roasted coffee oil (GCO, RCO) and heated (HGCO, HRCO) for 1 h at 200 degrees C, by Fourier Transform Infrared (FTIR) spectroscopy and in terms of antioxidant and antimicrobial properties. The results of FTIR spectroscopy revealed that no statistically significant differences (one-way ANOVA, p>0.05) in the oxidative status of GCO and RCO were found. The coffee oils heating induced significant spectral changes in the regions 3100-3600 cm(-1), 2800-3050 cm(-1) and 1680-1780 cm(-1) proved by the differences in the absorbance ratios A 3009 cm(-1)/A 2922 cm(-1), A 3009 cm(-1)/A 2853 cm(-1), A 3009 cm(-1)/A 1744 cm(-1), A 1744 cm(-1)/A 2922 cm(-1). These alterations were related to the reduction of the unsaturation degree due to primary and secondary oxidation processes of the lipid fraction. The radical scavenging ability of oils investigated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay revealed that the IC50 value of GCO was significantly lower than of RCO (p<0.05). The IC50 values of crude coffee oils were lower than those of heated samples. The antioxidant activity of oils was attributed to both antioxidant compounds with free-radical scavenging capacity and to lipids oxidation products generated by heating. In the first 6 h of incubation, the inhibitory activity of crude oils against E. coli and E. faecalis was not significantly different to the control (p>0.05). Also, HGCO and HRCO showed significantly different inhibitory potential related to the control (p<0.05). The heating induced statistically significant decreases in the effectiveness of coffee oils against the tested bacteria. GCO proved to be the most effective among investigated coffee oils against the tested bacteria. PMID- 26366732 TI - TIMP-1 Inhibits Apoptosis in Lung Adenocarcinoma Cells via Interaction with Bcl 2. AB - Tissue inhibitors of metalloproteinases (TIMPs) are multifaceted molecules that exhibit properties beyond their classical proteinase inhibitory function. Although TIMP-1 is a known inhibitor of apoptosis in mammalian cells, the mechanisms by which it exerts its effects are not well-established. Our earlier studies using H2009 lung adenocarcinoma cells, implanted in the CNS, showed that TIMP-1 overexpressing H2009 cells (HB-1), resulted in more aggressive tumor kinetics and increased vasculature. The present study was undertaken to elucidate the role of TIMP-1 in the context of apoptosis, using the same lung cancer cell lines. Overexpressing TIMP-1 in a lung adenocarcinoma cell line H2009 resulted in an approximately 3-fold increased expression of Bcl-2, with a marked reduction in apoptosis upon staurosporine treatment. This was an MMP-independent function as a clone expressing TIMP-1 mutant T2G, lacking MMP inhibition activity, inhibited apoptosis as strongly as TIMP1 overexpressing clones, as determined by inhibition of PARP cleavage. Immunoprecipitation of Bcl-2 from cell lysates also co immunoprecipitated TIMP-1, indicative of an interaction between these two proteins. This interaction was specific for TIMP-1 as TIMP-2 was not present in the Bcl-2 pull-down. Additionally, we show a co-dependency of TIMP-1 and Bcl-2 RNA and protein levels, such that abrogating Bcl-2 causes a downregulation of TIMP-1 but not TIMP-2. Finally, we demonstrate that TIMP-1 dependent inhibition of apoptosis occurs through p90RSK, with phosphorylation of the pro-apoptotic protein BAD at serine 112, ultimately reducing Bax levels and increasing mitochondrial permeability. Together, these studies define TIMP-1 as an important cancer biomarker and demonstrate the potential TIMP-1 as a crucial therapeutic target. PMID- 26366734 TI - Correction: Efficient Modeling of MS/MS Data for Metabolic Flux Analysis. PMID- 26366733 TI - Disruption of Daily Rhythms by High-Fat Diet Is Reversible. AB - In mammals a network of circadian clocks coordinates behavior and physiology with 24-h environmental cycles. Consumption of high-fat diet disrupts this temporal coordination by advancing the phase of the liver molecular clock and altering daily rhythms of eating behavior and locomotor activity. In this study we sought to determine whether these effects of high-fat diet on circadian rhythms were reversible. We chronically fed mice high-fat diet and then returned them to low fat chow diet. We found that the phase of the liver PERIOD2::LUCIFERASE rhythm was advanced (by 4h) and the daily rhythms of eating behavior and locomotor activity were altered for the duration of chronic high-fat diet feeding. Upon diet reversal, the eating behavior rhythm was rapidly reversed (within 2 days) and the phase of the liver clock was restored by 7 days of diet reversal. In contrast, the daily pattern of locomotor activity was not restored even after 2 weeks of diet reversal. Thus, while the circadian system is sensitive to changes in the macronutrient composition of food, the eating behavior rhythm and liver circadian clock are specifically tuned to respond to changes in diet. PMID- 26366735 TI - Assessing the Metabolic Diversity of Streptococcus from a Protein Domain Point of View. AB - Understanding the diversity and robustness of the metabolism of bacteria is fundamental for understanding how bacteria evolve and adapt to different environments. In this study, we characterised 121 Streptococcus strains and studied metabolic diversity from a protein domain perspective. Metabolic pathways were described in terms of the promiscuity of domains participating in metabolic pathways that were inferred to be functional. Promiscuity was defined by adapting existing measures based on domain abundance and versatility. The approach proved to be successful in capturing bacterial metabolic flexibility and species diversity, indicating that it can be described in terms of reuse and sharing functional domains in different proteins involved in metabolic activity. Additionally, we showed striking differences among metabolic organisation of the pathogenic serotype 2 Streptococcus suis and other strains. PMID- 26366736 TI - A Genetic Variant in the Distal Enhancer Region of the Human Renin Gene Affects Renin Expression. AB - BACKGROUND: The high heritability of plasma renin activity was confirmed in recent investigations. A variation located near the strong enhancer of the human renin gene (REN), C-5312T, has been shown to have different transcription activity levels depending on its allele: the 5312T allele shows transcription levels that are 45% greater than those of the 5312C allele. The purpose of this study was to confirm the hypothesis that variations in the enhancer region of the REN gene are involved in regulating renal expression of renin. METHODS: Sixty four subjects with biopsy-proven renal diseases were included in this study (male/female: 35/29, age 41.9 +/- 20.9 years, SBP/DBP 123.1 +/- 23.7/73.4 +/- 14.8 mmHg, s-Cr 0.93 +/- 0.63 mg/dl). A genetic variant of REN, C-5312T, was assayed by PCR-RFLP and the TaqMan method. Total RNAs from a small part of the renal cortex were reverse-transcribed and amplified for REN and GAPDH with a real time PCR system. RESULTS: Logarithmically transformed expression values of the relative ratio of REN to GAPDH (10-3) were as follows (mean +/- SE): CC (26 cases), 0.016 +/- 0.005; CT (33 cases), 0.047 +/- 0.021 (p = 0.41 vs. CC); TT (5 cases), 0.198 +/- 0.194 (p = 0.011 vs. CC, p < 0.031 vs. CT). Thus, significant differences in REN expression were observed among the genetic variants. CONCLUSION: The results suggest that variants in the enhancer region of the human renin gene have an effect on the expression levels of renin in renal tissue; this observation is in good accordance with the results of the transcriptional assay. PMID- 26366737 TI - Gene Co-Expression Analysis Inferring the Crosstalk of Ethylene and Gibberellin in Modulating the Transcriptional Acclimation of Cassava Root Growth in Different Seasons. AB - Cassava is a crop of hope for the 21st century. Great advantages of cassava over other crops are not only the capacity of carbohydrates, but it is also an easily grown crop with fast development. As a plant which is highly tolerant to a poor environment, cassava has been believed to own an effective acclimation process, an intelligent mechanism behind its survival and sustainability in a wide range of climates. Herein, we aimed to investigate the transcriptional regulation underlying the adaptive development of a cassava root to different seasonal cultivation climates. Gene co-expression analysis suggests that AP2-EREBP transcription factor (ERF1) orthologue (D142) played a pivotal role in regulating the cellular response to exposing to wet and dry seasons. The ERF shows crosstalk with gibberellin, via ent-Kaurene synthase (D106), in the transcriptional regulatory network that was proposed to modulate the downstream regulatory system through a distinct signaling mechanism. While sulfur assimilation is likely to be a signaling regulation for dry crop growth response, calmodulin-binding protein is responsible for regulation in the wet crop. With our initiative study, we hope that our findings will pave the way towards sustainability of cassava production under various kinds of stress considering the future global climate change. PMID- 26366738 TI - Protection Induced in Broiler Chickens following Drinking-Water Delivery of Live Infectious Laryngotracheitis Vaccines against Subsequent Challenge with Recombinant Field Virus. AB - Infectious laryngotracheitis virus (ILTV) causes acute upper respiratory tract disease in chickens. Attenuated live ILTV vaccines are often used to help control disease, but these vaccines have well documented limitations, including retention of residual virulence, incomplete protection, transmission of vaccine virus to unvaccinated birds and reversion to high levels of virulence following bird-to bird passage. Recently, two novel ILTV field strains (class 8 and 9 ILTV viruses) emerged in Australia due to natural recombination between two genotypically distinct commercial ILTV vaccines. These recombinant field strains became dominant field strains in important poultry producing areas. In Victoria, Australia, the recombinant class 9 virus largely displaced the previously predominant class 2 ILTV strain. The ability of ILTV vaccines to protect against challenge with the novel class 9 ILTV strain has not been studied. Here, the protection induced by direct (drinking-water) and indirect (contact) exposure to four different ILTV vaccines against challenge with class 9 ILTV in commercial broilers was studied. The vaccines significantly reduced, but did not prevent, challenge virus replication in vaccinated chickens. Only one vaccine significantly reduced the severity of tracheal pathology after direct drinking water vaccination. The results indicate that the current vaccines can be used to help control class 9 ILTV, but also indicate that these vaccines have limitations that should be considered when designing and implementing disease control programs. PMID- 26366740 TI - Correction: Translation Elongation Factor Tuf of Acinetobacter baumannii Is a Plasminogen-Binding Protein. PMID- 26366739 TI - Transient Loss of Protection Afforded by a Live Attenuated Non-typhoidal Salmonella Vaccine in Mice Co-infected with Malaria. AB - In immunocompetent individuals, non-typhoidal Salmonella serovars (NTS) are associated with gastroenteritis, however, there is currently an epidemic of NTS bloodstream infections in sub-Saharan Africa. Plasmodium falciparum malaria is an important risk factor for invasive NTS bloodstream in African children. Here we investigated whether a live, attenuated Salmonella vaccine could be protective in mice, in the setting of concurrent malaria. Surprisingly, mice acutely infected with the nonlethal malaria parasite Plasmodium yoelii 17XNL exhibited a profound loss of protective immunity to NTS, but vaccine-mediated protection was restored after resolution of malaria. Absence of protective immunity during acute malaria correlated with maintenance of antibodies to NTS, but a marked reduction in effector capability of Salmonella-specific CD4 and CD8 T cells. Further, increased expression of the inhibitory molecule PD1 was identified on memory CD4 T cells induced by vaccination. Blockade of IL-10 restored protection against S. Typhimurium, without restoring CD4 T cell effector function. Simultaneous blockade of CTLA-4, LAG3, and PDL1 restored IFN-gamma production by vaccine induced memory CD4 T cells but was not sufficient to restore protection. Together, these data demonstrate that malaria parasite infection induces a temporary loss of an established adaptive immune response via multiple mechanisms, and suggest that in the setting of acute malaria, protection against NTS mediated by live vaccines may be interrupted. PMID- 26366741 TI - The Fitness Effects of Love. AB - A study of zebra finches reveals the potential advantages of idiosyncratic mate choice in monogamous animal species. Read the Research Article. PMID- 26366743 TI - High-Throughput Screening for Ligands of the HEPN Domain of Sacsin. AB - Sacsin is a large protein implicated in the neurodevelopmental and neurodegenerative disease autosomal recessive spastic ataxia of Charlevoix Saguenay (ARSACS), which features the loss of Purkinje neurons in the cerebellum. Although the domain architecture of sacsin suggests that it is a neuronal chaperone assisting in protein quality control, the precise function of sacsin remains elusive. Using fluorescence polarization (FP) assays, we confirmed that the HEPN domain of sacsin binds to nucleotides with low micromolar affinities. FP competition assays with a variety of nucleotides and nucleotide analogs revealed that the binding is primarily mediated by the phosphate groups of nucleotides. A high-throughput screen subsequently identified novel small molecule ligands of HEPN, providing new chemical probes for cell culture studies and drug development. Together, the results are consistent with the HEPN domain contributing to the functional activity of sacsin by binding to nucleotides or other multiply charged anionic compounds in neurons. PMID- 26366742 TI - Characterization of the FKBP12-Encoding Genes in Aspergillus fumigatus. AB - Invasive aspergillosis, largely caused by Aspergillus fumigatus, is responsible for a growing number of deaths among immunosuppressed patients. Immunosuppressants such as FK506 (tacrolimus) that target calcineurin have shown promise for antifungal drug development. FK506-binding proteins (FKBPs) form a complex with calcineurin in the presence of FK506 (FKBP12-FK506) and inhibit calcineurin activity. Research on FKBPs in fungi is limited, and none of the FKBPs have been previously characterized in A. fumigatus. We identified four orthologous genes of FKBP12, the human FK506 binding partner, in A. fumigatus and designated them fkbp12-1, fkbp12-2, fkbp12-3, and fkbp12-4. Deletional analysis of the four genes revealed that the Deltafkbp12-1 strain was resistant to FK506, indicating FKBP12-1 as the key mediator of FK506-binding to calcineurin. The endogenously expressed FKBP12-1-EGFP fusion protein localized to the cytoplasm and nuclei under normal growth conditions but also to the hyphal septa following FK506 treatment, revealing its interaction with calcineurin. The FKBP12-1-EGFP fusion protein didn't localize at the septa in the presence of FK506 in the cnaA deletion background, confirming its interaction with calcineurin. Testing of all deletion strains in the Galleria mellonella model of aspergillosis suggested that these proteins don't play an important role in virulence. While the Deltafkbp12-2 and Deltafkbp12-3 strains didn't show any discernable phenotype, the Deltafkbp12 4 strain displayed slight growth defect under normal growth conditions and inhibition of the caspofungin-mediated "paradoxical growth effect" at higher concentrations of the antifungal caspofungin. Together, these results indicate that while only FKBP12-1 is the bona fide binding partner of FK506, leading to the inhibition of calcineurin in A. fumigatus, FKBP12-4 may play a role in basal growth and the caspofungin-mediated paradoxical growth response. Exploitation of differences between A. fumigatus FKBP12-1 and human FKBP12 will be critical for the generation of fungal-specific FK506 analogs to inhibit fungal calcineurin and treat invasive fungal disease. PMID- 26366744 TI - Correction of image drift and distortion in a scanning electron microscopy. AB - Continuous research on small-scale mechanical structures and systems has attracted strong demand for ultrafine deformation and strain measurements. Conventional optical microscope cannot meet such requirements owing to its lower spatial resolution. Therefore, high-resolution scanning electron microscope has become the preferred system for high spatial resolution imaging and measurements. However, scanning electron microscope usually is contaminated by distortion and drift aberrations which cause serious errors to precise imaging and measurements of tiny structures. This paper develops a new method to correct drift and distortion aberrations of scanning electron microscope images, and evaluates the effect of correction by comparing corrected images with scanning electron microscope image of a standard sample. The drift correction is based on the interpolation scheme, where a series of images are captured at one location of the sample and perform image correlation between the first image and the consequent images to interpolate the drift-time relationship of scanning electron microscope images. The distortion correction employs the axial symmetry model of charged particle imaging theory to two images sharing with the same location of one object under different imaging fields of view. The difference apart from rigid displacement between the mentioned two images will give distortion parameters. Three-order precision is considered in the model and experiment shows that one pixel maximum correction is obtained for the employed high-resolution electron microscopic system. PMID- 26366745 TI - Are obsessive-compulsive symptoms expression of vulnerability to bipolar disorder? PMID- 26366746 TI - Multifunctional Magnetic Gd(3+) -Based Coordination Polymer Nanoparticles: Combination of Magnetic Resonance and Multispectral Optoacoustic Detections for Tumor-Targeted Imaging in vivo. AB - To overcome traditional barriers in optical imaging and microscopy, optoacoustic imaging has been changed to combine the accuracy of spectroscopy with the depth resolution of ultrasound, achieving a novel modality with powerful in vivo imaging. However, magnetic resonance imaging provides better spatial and anatomical resolution. Thus, a single hybrid nanoprobe that allows for simultaneous multimodal imaging is significant not only for cutting edge research in imaging science, but also for accurate clinical diagnosis. A core-shell structured coordination polymer composite microsphere has been designed for in vivo multimodality imaging. It consists of a Fe3 O4 nanocluster core, a carbon sandwiched layer, and a carbocyanine-Gd(III) (Cy-Gd(III) ) coordination polymer outer shell (Fe3 O4 @C@Cy-Gd(III) ). Folic acid-conjugated poly(ethylene glycol) chains are embedded within the coordination polymer shell to achieve extended circulation and targeted delivery of probe particles in vivo. Control of Fe3 O4 core grain sizes results in optimal r2 relaxivity (224.5 * 10(-3) m(-1) s(-1) ) for T2 -weighted magnetic resonance imaging. Cy-Gd(III) coordination polymers are also regulated to obtain a maximum 25.1% of Cy ligands and 5.2% of Gd(III) ions for near-infrared fluorescence and T1 -weighted magnetic resonance imaging, respectively. The results demonstrate their impressive abilities for targeted, multimodal, and reliable imaging. PMID- 26366747 TI - Development of Enantioselective Palladium-Catalyzed Alkene Carboalkoxylation Reactions for the Synthesis of Tetrahydrofurans. AB - The Pd-catalyzed coupling of gamma-hydroxyalkenes with aryl bromides affords enantiomerically enriched 2-(arylmethyl)tetrahydrofuran derivatives in good yield and up to 96:4 e.r. This transformation was achieved through the development of a new TADDOL/2-arylcyclohexanol-derived chiral phosphite ligand. The transformations are effective with an array of different aryl bromides, and can be used for the preparation of products bearing quaternary stereocenters. PMID- 26366748 TI - Neural correlates of temporal summation of second pain in the human brainstem and spinal cord. AB - Temporal summation of second pain (TSSP) occurs when painful stimuli are presented repetitively (>= 0.33 Hz) and results from a C-fibre evoked enhancement (or "wind-up") of the dorsal horn neurons. Based on electrophysiological studies in intact animals, windup is considered a purely central phenomenon. With advancements in functional MRI (fMRI), we can now probe the central mechanisms of this pain response in humans. The aim of this study is to characterize the fMRI responses in the healthy human brainstem and spinal cord that correspond to TSSP. Functional MRI of healthy female adults (N = 15) was conducted while brief, repetitive heat pain stimuli were applied to the right thenar eminence (C6 dermatome), and TSSP (0.33 Hz) and control (0.17 Hz) heat pain paradigms were employed. The stimulus intensity was adjusted to each participant's heat pain sensitivity. Data were analyzed by means of a general linear model, and region-of interest analyses. As predicted, participants demonstrated significant behavioural summation of pain in the TSSP condition. FMRI results identified enhanced activity in the spinal cord dorsal horn at C6 in response to the TSSP condition. Additionally, multiple areas of the brainstem (RVM and PAG) showed greater responses with the TSSP condition. These results suggest that, in humans, increased pain perception in the TSSP condition is reflected by greater responses in the dorsal horn and in regions known to play a role in the descending modulation of pain, which may modulate the spinal cord response. PMID- 26366749 TI - Plasma-Synthesized Silver Nanoparticles on Electrospun Chitosan Nanofiber Surfaces for Antibacterial Applications. AB - Chitosan nanofibers have been electrospun with poly(ethylene oxide) and silver nitrate, as a coelectrospinning polymer and silver nanoparticle precursor, respectively. The average diameter of the as-spun chitosan nanofibers with up to 2 wt % silver nitrate loading was approximately 130 nm, and there was no evidence of bead formation or polymer agglomeration. Argon plasma was then applied for surface etching and synthesis of silver nanoparticles via precursor decomposition. Plasma surface bombardment induced nanoparticle formation primarily on the chitosan nanofiber surfaces, and the moderate surface plasma etching further encouraged maximum exposure of silver nanoparticles. UV-vis spectra showed the surface plasmon resonance signature of silver nanoparticles. The surface-immobilized nanoparticles were visualized by TEM and were found to have average particle diameters as small as 1.5 nm. Surface analysis by infrared spectroscopy and X-ray photoelectron spectroscopy confirmed the interactions between the silver nanoparticles and chitosan molecules, as well as the effect of plasma treatment on the nanofiber surfaces. Finally, a bacteria inhibition study revealed that the antibacterial activity of the electrospun chitosan nanofibers correspondingly increased with the plasma-synthesized silver nanoparticles. PMID- 26366750 TI - Protective Effects of the Total Coumarin Fraction of Urtica dentata on Experimental Diabetic Nephropathy In Vitro and In Vivo. AB - We previously reported that total coumarins, the major active components of Urtica dentata Hand, exhibited substantial protection against the development of autoimmune diabetes. Diabetic nephropathy is one of the most serious complications of diabetes and is closely correlated with end-stage renal disease. We used the rat glomerular mesangial cell line (HBZY-1) and streptozotocin induced diabetic rats to investigate the potential protective effects and mechanisms of total coumarins on diabetic renal disease. Our data revealed that total coumarins inhibited high glucose-induced HBZY-1 cell proliferation and hypertrophy, and produced its effects through downregulating transforming growth factor-beta1, connective tissue growth factor, and toll-like receptor 4 activation. Consistent with those findings, total coumarins administration in a diabetic model had anti-renal lesion effects in vivo. Total coumarins, at a dose of 50 or 100 mg/kg: 1) significantly increased body weight; 2) ameliorated morphological evidence of renal pathology; 3) decreased blood levels of glucose and urea nitrogen; 4) decreased albuminuria and serum creatinine; and 5) reduced protein and gene levels of transforming growth factor-beta1, connective tissue growth factor, and toll-like receptor 4 in the kidneys. These results support the view that total coumarins treatment can be substantially renoprotective in DN. PMID- 26366751 TI - Vitamin D Receptor-Mediated Upregulation of CYP3A4 and MDR1 by Quercetin in Caco 2 cells. AB - To examine whether quercetin interacts with vitamin D receptor, we investigated the effects of quercetin on vitamin D receptor activity in human intestinal Caco 2 cells. The effects of quercetin on the expression of the vitamin D receptor target genes, vitamin D3 24-hydroxylase, cytochrome P450 3A4, multidrug resistance protein 1, and transient receptor potential vanilloid type 6 were measured using quantitative polymerase chain reaction. The vitamin D receptor siRNA was used to assess the involvement of the vitamin D receptor. Vitamin D receptor activation using a vitamin D responsive element-mediated cytochrome P450 3A4 reporter gene assay was investigated in Caco-2 cells transfected with human vitamin D receptor. We also studied the magnitude of the vitamin D receptor activation and/or synergism between 1alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3] and quercetin-like flavonoids. Slight but significant increases in the mRNA expression of cytochrome P450 3A4, vitamin D3 24-hydroxylase, multidrug resistance protein 1, and transient receptor potential vanilloid type 6 were observed after 3 days of continual quercetin treatment. The silencing effect of vitamin D receptor by vitamin D receptor siRNA in Caco-2 cells significantly attenuated the induction of the vitamin D receptor target genes. Moreover, quercetin significantly enhanced cytochrome P450 3A4 reporter activity in Caco-2 cells in a dose-dependent manner, and the expression of exogenous vitamin D receptor further stimulated the vitamin D receptor activity. Quercetin-like flavonoids such as kaempferol stimulated the vitamin D receptor activity in a manner similar to that seen with quercetin. Taken together, the data indicates that quercetin upregulates cytochrome P450 3A4 and multidrug resistance protein 1 expression in Caco-2 cells likely via a vitamin D receptor-dependent pathway. PMID- 26366752 TI - Toxicological, Antidiarrheal and Spasmolytic Activities of Solanum paniculatum. AB - Solanum paniculatum is popularly known as "jurubeba-verdadeira". In folk medicine, its roots, stems, and leaves are used as tonics, anti-inflammatories, carminatives, diuretics, and for gastrointestinal disorders. This species is listed in the Brazilian Pharmacopoeia and belongs to the "Relacao Nacional de Plantas Medicinais de Interesse ao SUS". Based on folk medicine data of the Solanum genus, we decided to investigate whether the crude ethanol extract from S. paniculatum aerial parts presents toxicological, antidiarrheal, and spasmolytic activities. The crude ethanol extract from S. paniculatum aerial parts did not produce in vitro or in vivo toxicity and showed dose-dependent antidiarrheal activity, inhibiting equipotently both the defecation frequency (ED50 = 340.3 +/- 35.1 mg/kg) and liquid stool formation (ED50 = 370.1 +/- 19.4 mg/kg) in mice. Conversely, the crude ethanol extract from S. paniculatum aerial parts did not inhibit normal intestinal transit, even though it has shown a dose dependent reduction of both the castor oil-induced intestinal transit (Emax = 36.9 +/- 1.3 %, ED50 = 242.0 +/- 8.6 mg/kg) and intestinal fluid content (Emax = 74.8 +/- 2.4 %, ED50 = 328.9 +/- 15.9 mg/kg). Additionally, the crude ethanol extract from S. paniculatum aerial parts was approximately 2-fold more potent in antagonizing the phasic contractions induced with histamine (IC50 = 63.7 +/- 3.5 ug/mL) than carbachol 10(-6) M (IC50 = 129.3 +/- 14.1 ug/mL). Therefore, we concluded that the crude ethanol extract from S. paniculatum aerial parts presents antidiarrheal activity in mice related to the inhibition of small intestinal motility and secretion as well as nonselective spasmolytic activity on the guinea pig ileum. PMID- 26366753 TI - Houttuyniae Herba Attenuates Kainic Acid-Induced Neurotoxicity via Calcium Response Modulation in the Mouse Hippocampus. AB - Epilepsy is a complex neurological disorder characterized by the repeated occurrence of electrical activity known as seizures. This activity induces increased intracellular calcium, which ultimately leads to neuronal damage. Houttuyniae Herba, the aerial part of Houttuynia cordata, has various pharmacological effects and is widely used as a traditional herb. In the present study, we evaluated the protective effects of Houttuyniae Herba water extract on kainic acid-induced neurotoxicity. Kainic acid directly acts on calcium release, resulting in seizure behavior, neuronal damage, and cognitive impairment. In a rat primary hippocampal culture system, Houttuyniae Herba water extract significantly protected neuronal cells from kainic acid toxicity. In a seizure model where mice received intracerebellar kainic acid injections, Houttuyniae Herba water extract treatment resulted in a lower seizure stage score, ameliorated cognitive impairment, protected neuronal cells against kainic acid induced toxicity, and suppressed neuronal degeneration in the hippocampus. In addition, Houttuyniae Herba water extract regulated increases in the intracellular calcium level, its related downstream pathways (reactive oxygen species production and mitochondrial dysfunction), and calcium/calmodulin complex kinase type II immunoreactivity in the mouse hippocampus, which resulted from calcium influx stimulation induced by kainic acid. These results demonstrate the neuroprotective effects of Houttuyniae Herba water extract through inhibition of calcium generation in a kainic acid-induced epileptic model. PMID- 26366754 TI - Supercritical Fluid Chromatography as an Alternative Tool for the Qualitative and Quantitative Analysis of Metarhizium brunneum Metabolites from Culture Broth. AB - A fast and selective ultrahigh-performance supercritical fluid chromatography photodiode array detector method was established for the qualitative and quantitative analysis of destruxins, cyclic hexadepsipeptides, from fungal culture broth samples. Prior to analysis, sample purification was carried out using an off-line solid-phase extraction protocol on a reversed-phase material in order to remove unwanted matrix constituents. For separation, detection, and identification, an ultrahigh-performance supercritical fluid chromatography photodiode array detector system hyphenated to a triple quadrupole mass spectrometer was utilized. Analyses were performed on an Acquity ethylene bridged hybrid 2-ethylpyridine sub 2 um particle size column with CO2 and an acidified (0.02% trifluor acetic acid) modifier mixture of methanol/acetonitrile (8/2 v/v) serving as mobile phase. For the optimal separation of destruxins, the amount of the modifier was increased in a 10 min linear gradient from 2% to 20%, and the column outlet pressure and temperature was set at 140 bars and 60 degrees C, respectively. Seventeen analytes were separated within an elution window of 4 minutes. Five destruxin congeners (destruxin A, destruxin B, destruxin D, destruxin E, and destruxin E-diol) were identified using reference material. Additionally, eight analytes were tentatively assigned as known destruxins by the evaluation of mass spectrometry data performed as multiple reaction monitoring experiments in the positive electrospray ionization mode. PMID- 26366756 TI - The Pharmacological Activities of Licorice. AB - Licorice is one of the oldest and most frequently used herbs in traditional Chinese medicine. It contains more than 20 triterpenoids and 300 flavonoids. In recent years, a lot of studies have reported that the active compounds isolated from licorice possess antitumor, antimicrobial, antiviral, anti-inflammatory, immunoregulatory, and several other activities that contribute to the recovery and protection of the nervous, alimentary, respiratory, endocrine, and cardiovascular systems. In this paper, nine different pharmacological activities of licorice are summarized. The active compounds responsible for these pharmacological activities, the molecular mechanisms, and in vivo and in vitro studies are listed in detail. Furthermore, the clinical therapeutics and toxicity studies of licorice are also discussed. We hope this work can provide a basis for further studies concerning with the safe and effective use of licorice. PMID- 26366755 TI - Black Cumin (Nigella sativa) and Its Active Constituent, Thymoquinone: An Overview on the Analgesic and Anti-inflammatory Effects. AB - For many centuries, seeds of Nigella sativa (black cumin), a dicotyledon of the Ranunculaceae family, have been used as a seasoning spice and food additive in the Middle East and Mediterranean areas. Traditionally, the plant is used for asthma, hypertension, diabetes, inflammation, cough, bronchitis, headache, eczema, fever, dizziness, and gastrointestinal disturbances. The literature regarding the biological activities of seeds of this plant is extensive, citing bronchodilative, anti-inflammatory, antinociceptive, antibacterial, hypotensive, hypolipidemic, cytotoxic, antidiabetic, and hepatoprotective effects. The active ingredients of N. sativa are mainly concentrated in the fixed or essential oil of seeds, which are responsible for most health benefits. This review will provide all updated reported activities of this plant with an emphasis on the antinociceptive and anti-inflammatory effects. Results of various studies have demonstrated that the oil, extracts, and their active ingredients, in particular, thymoquinone, possess antinociceptive and anti-inflammatory effects, supporting the common folk perception of N. Sativa as a potent analgesic and anti inflammatory agent. Many protective properties are attributed to reproducible radical scavenging activity as well as an interaction with numerous molecular targets involved in inflammation, including proinflammatory enzymes and cytokines. However, there is a need for further investigations to find out the precise mechanisms responsible for the antinociceptive and anti-inflammatory effects of this plant and its active constituents. PMID- 26366757 TI - The Role of Catalysis in Alkanediol Decomposition: Implications for General Detection of Alkanediols and Their Formation in the Atmosphere. AB - Quantum chemical calculations have been carried out to investigate the gas-phase structure, stability, and decomposition of the two simplest alkanediols, methanediol and 1,1-ethanediol, in the presence of various catalysts. Three different conformers for monomeric alkanediols namely cis, trans, and trans' were considered. The calculations reveal that alkanediols may exist not only as monomers but also as dimers that have high binding energies of 7-11 kcal/mol due to hydrogen bonding among the oxygenate functionalities. Some of these dimers have high dipole moments and, thus, may be more easily detected experimentally than the monomers of alkanediols. For the decomposition of alkanediols, the calculations dominantly favor dehydration over dehydrogenation. The relatively low barrier for the decomposition of 1,1-ethanediol suggests that the structure of an alkanediol plays a role in its decomposition. Though the dehydration of alkanediols with or without water catalyst involves large barriers, organic and inorganic acids, the hydroperoxyl radical catalytically influences the reaction to such an extent that the dehydration reaction either involves significantly reduced barriers or essentially becomes barrierless. Considering that alkanediols contain hydroxyl groups and their dimers have high binding energies, the gas phase dehydration may be self-driven. Because acids are present in significant amounts in the troposphere, results suggest that diol dehydration may be facile under atmospheric conditions. PMID- 26366758 TI - Performance analysis of cone detection algorithms. AB - Many algorithms have been proposed to help clinicians evaluate cone density and spacing, as these may be related to the onset of retinal diseases. However, there has been no rigorous comparison of the performance of these algorithms. In addition, the performance of such algorithms is typically determined by comparison with human observers. Here we propose a technique to simulate realistic images of the cone mosaic. We use the simulated images to test the performance of three popular cone detection algorithms, and we introduce an algorithm which is used by astronomers to detect stars in astronomical images. We use Free Response Operating Characteristic (FROC) curves to evaluate and compare the performance of the four algorithms. This allows us to optimize the performance of each algorithm. We observe that performance is significantly enhanced by up-sampling the images. We investigate the effect of noise and image quality on cone mosaic parameters estimated using the different algorithms, finding that the estimated regularity is the most sensitive parameter. PMID- 26366759 TI - Analytical models for electrically thin flat lenses and reflectors. AB - This work presents analytical models for two-dimensional (2D) and three dimensional (3D) electrically thin lenses and reflectors. The 2D formulation is based on infinite current line sources, whereas the 3D formulation is based on electrically small dipoles. These models emulate the energy convergence of an electrically thin flat lens and reflector when illuminated by a plane wave with specific polarization. The advantages of these models are twofold: first, prediction of the performance of electrically thin flat lenses and reflectors can be made significantly faster than full-wave simulators, and second, providing insight on the performance of these electrically thin devices. The analytic models were validated by comparison with full-wave simulation for several interesting examples. The validation results show that the focal point of the electrically thin flat lenses and reflectors can be accurately predicted through a design that assumes low coupling between different layers of an inhomogeneous media. PMID- 26366760 TI - Internal energy flows of coma-affected singular beams in low-numerical-aperture systems. AB - The circulating phase gradient component of a singular beam gets modified when focused by a low-numerical-aperature system suffering from coma aberration. The gradient due to this coma aberration splits the higher charge vortex into elementary vortices and distributes them spatially. This splitting depends on the charge and polarity of the incident singular beam as well as the sign and magnitude of the aberration coefficient. The transverse component of the Poynting vector field distribution at the focal plane is decomposed into the curl or solenoidal component and divergence or irrotational component using the Helmholtz Hodge decomposition technique. The solenoidal component that relates to the orbital angular momentum carries the circulating energy, while the irrotational component shows the sources and sinks of the energy. Intriguing results of the study of energy flow around the edge dislocations apart from the point phase defects in the irrotational components are also presented. PMID- 26366761 TI - Poynting theorem constraints on the signs of the imaginary parts of the electromagnetic constitutive parameters. AB - In time harmonic analysis, media composed of sub-wavelength metallic or dielectric inclusions are described by complex and dispersive effective constitutive parameters. A study of such parameters based on the conservation law of energy and causality is presented. We derive a set of general constraints on the real and imaginary parts of the constitutive parameters for lossy and lossless media in terms of electric and magnetic loss tangents. It is shown that a passive medium can indeed have a negative imaginary part of either the permeability or permittivity over a range of frequencies. These findings are consistent with the principles of causality and energy conservation. PMID- 26366762 TI - Photospectroscopically observed pore-space correlations of a wetting fluid during the drying process in nanoporous Vycor glass. AB - We use light scattering to study spatial correlations in the pore space of Vycor glass upon draining a wetting fluid. We analyze the transmission spectrum of forward-scattered light on the basis of the theory of dielectric constant fluctuation, whereas conventional light scattering analyzes the scattered light at small angles of monochromatic incident light. Assuming that the drained pores, which are surrounded by filled pores, exhibit long-range correlations of a fractal dimension of 2.5, we analytically derive the corresponding turbidity. The slight deviation from the lambda(-4) Rayleigh wavelength dependence directly provides the correlation length of the interconnected network of drained pores. The estimated length, ranging from 0.5 to 18 nm at most, is almost the same order as that indirectly estimated from our previous simple effective Rayleigh scatterer model. PMID- 26366763 TI - Metric for the measurement of the quality of complex beams: a theoretical study. AB - We present a theoretical study of various definitions of laser beam width in a given cross section. Quality of the beam is characterized by dimensionless beam propagation products (BPPs) Deltax.Deltatheta(x)/lambda, which are different for the 21 definitions presented, but are close to 1. Six particular beams are studied in detail. In the process, we had to review the properties for the Fourier transform of various modifications and the relationships between them: physical Fourier transform (PFT), mathematical Fourier transform (MFT), and discrete Fourier transform (DFT). We found an axially symmetric self-MFT function, which may be useful for descriptions of diffraction-quality beams. In the appendices, we illustrate the thesis "the Fourier transform lives on the singularities of the original." PMID- 26366764 TI - Method for optimizing channelized quadratic observers for binary classification of large-dimensional image datasets. AB - We present a new method for computing optimized channels for channelized quadratic observers (CQO) that is feasible for high-dimensional image data. The method for calculating channels is applicable in general and optimal for Gaussian distributed image data. Gradient-based algorithms for determining the channels are presented for five different information-based figures of merit (FOMs). Analytic solutions for the optimum channels for each of the five FOMs are derived for the case of equal mean data for both classes. The optimum channels for three of the FOMs under the equal mean condition are shown to be the same. This result is critical since some of the FOMs are much easier to compute. Implementing the CQO requires a set of channels and the first- and second-order statistics of channelized image data from both classes. The dimensionality reduction from M measurements to L channels is a critical advantage of CQO since estimating image statistics from channelized data requires smaller sample sizes and inverting a smaller covariance matrix is easier. In a simulation study we compare the performance of ideal and Hotelling observers to CQO. The optimal CQO channels are calculated using both eigenanalysis and a new gradient-based algorithm for maximizing Jeffrey's divergence (J). Optimal channel selection without eigenanalysis makes the J-CQO on large-dimensional image data feasible. PMID- 26366765 TI - Manifold regularized semi-supervised Gaussian mixture model. AB - In the last decades, Gaussian Mixture Models (GMMs) have attracted considerable interest in data mining and pattern recognition. A GMM-based clustering algorithm models a dataset with a mixture of multiple Gaussian components and estimates the model parameters using the Expectation-Maximization (EM) algorithm. Recently, a new Locally Consistent GMM (LCGMM) has been proposed to improve the clustering performance by exploiting the local manifold structure of the data using a p nearest neighbor graph. In addition to the underlying manifold structure, many other forms of prior knowledge may guide the clustering process and improve the performance. In this paper, we introduce a Semi-Supervised LCGMM (Semi-LCGMM), where the prior knowledge is provided in the form of class labels of partial data. In particular, the new Semi-LCGMM incorporates the prior knowledge into the maximum likelihood function of the original LCGMM, and the model parameters are estimated using the EM algorithm. It is worth noting that, in our algorithm, each class may be modeled by multiple Gaussian components while in the unsupervised setting each class is modeled by a single Gaussian component. Our algorithm has shown promising results in many different applications, including clustering breast cancer data, heart disease data, handwritten digit images, human face images, and image segmentation. PMID- 26366766 TI - Understanding disability glare: light scatter and retinal illuminance as predictors of sensitivity to contrast. AB - The presence of a bright light in the visual field has two main effects on the retinal image: reduced contrast and increased retinal illuminance because of scattered light; the latter can, under some conditions, lead to an improvement in retinal sensitivity. The combined effect remains poorly understood, particularly at low light levels. A psychophysical flicker-cancellation test was used to measure the amount and angular distribution of scattered light in the eye for 40 observers. Contrast thresholds were measured using a functional contrast sensitivity test. Pupil-plane glare-source illuminances (i.e., 0, 1.35, and 19.21 lm/m2), eccentricities (5 degrees , 10 degrees , and 15 degrees ), and background luminances (1, 2.6, and 26 cd/m2) were investigated. Visual performance was better than predicted, based on a loss of retinal image contrast caused by scattered light, particularly in the mesopic range. Prediction accuracy improved significantly when the expected increase in retinal sensitivity in the presence of scattered light was also incorporated in the model. PMID- 26366767 TI - Modified reciprocity relation for the time-dependent diffusion equation. AB - The classical reciprocity relation of radiative transfer fails for two points placed in regions having different indices of refraction. A modified reciprocity relation that involves the relative refractive index between the two points considered was previously derived for the continuous wave (cw) radiative transfer equation and for the cw diffusion equation (DE) [J. Opt. Soc. Am. A14, 486 (1997)]. In this paper, we extend these findings to the time-dependent DE and we discuss some implications to diffuse optical tomography. PMID- 26366768 TI - Intensity fluctuations of multimode laser beams in underwater medium. AB - In an oceanic optical communications link, the received intensity fluctuations, quantified by the scintillation index, are formulated and evaluated when a multimode laser is used. The variations of the scintillation index versus the oceanic turbulence parameters are examined for different multimode laser structures. Oceanic turbulence parameters used are the rate of dissipation of kinetic energy per unit mass of fluid, the rate of dissipation of mean-squared temperature, the Kolmogorov inner scale, and the parameter w that defines the ratio of temperature to salinity contributions to the refractive index spectrum. The results in this paper can be used to improve performance in the design of oceanic optical communications links. PMID- 26366769 TI - Mirage is an image in a flat ground surface. AB - Mirage is a fascinating phenomenon that has attracted many scientists to report their observations and descriptions about it. There are two different approaches to mirage formation. The more popular one is attributed to total internal reflection that occurs in the near ground air layers on hot sunny days. According to the other approach, mirage is an image in a rough surface that is observed at grazing angles of incidence. Most of the existing descriptions are qualitative and some include calculations based on guessing temperature change with no concrete experiments. In this report, first we show that Fermat's principle also concerns the wave nature of light and covers the constructive and destructive interference that is essential for image formation. Then, we provide a brief review of the image formation theory in a rough plane and demonstrate by experiments in the lab and deserts that the temperature gradient in the near ground air layers does not lead to mirage formation. PMID- 26366770 TI - Interpretation of azimuthal angle dependence of periodic gratings in Mueller matrix spectroscopic ellipsometry. AB - Mueller matrix spectroscopic ellipsometry becomes increasingly important for determining structural parameters of periodic line gratings. Because of the anisotropic character of gratings, the measured Mueller matrix elements are highly azimuthal angle dependent. Measurement results are interpreted by basic principles of diffraction on gratings. The spectral and azimuthal angle dependent intensity changes are correlated to so-called Rayleigh singularities, i.e., wavelengths where the number of diffraction orders changes. The positions of the Rayleigh singularities are calculated analytically and overlapped with measured spectra of two different types of photomasks with transparent and reflecting substrates. For both types of gratings, the Rayleigh singularities reproduce the contours of the spectra. Increasing grating periods result in a shift of these contours to longer wavelengths. Characteristic differences between the two photomasks are explained by the influence of the transmission orders, which are determined by the substrate transparency. PMID- 26366771 TI - Theory and operational rules for the discrete Hankel transform. AB - Previous definitions of a discrete Hankel transform (DHT) have focused on methods to approximate the continuous Hankel integral transform. In this paper, we propose and evaluate the theory of a DHT that is shown to arise from a discretization scheme based on the theory of Fourier-Bessel expansions. The proposed transform also possesses requisite orthogonality properties which lead to invertibility of the transform. The standard set of shift, modulation, multiplication, and convolution rules are derived. In addition to the theory of the actual manipulated quantities which stand in their own right, this DHT can be used to approximate the continuous forward and inverse Hankel transform in the same manner that the discrete Fourier transform is known to be able to approximate the continuous Fourier transform. PMID- 26366772 TI - Diffraction of a focused wave by an aperture: a new perspective. AB - A new approach for calculating the field in the focal region along lines through the focal point of a lens is presented. In particular, the method is applied to a circular aperture. It is also applied to other shaped apertures, including circular sectors or segments, such as a semicircular aperture or Hilbert mask, and to polygonal shapes. The diffracted field is calculated by a one-dimensional Fourier transform, and can be used for accurate calculation at observation points distant from the focus. The approach gives new insight to appreciating the asymptotic behavior of the diffracted field, and the existence of intensity zeros, for different aperture shapes. PMID- 26366773 TI - Vertical mode expansion method for analyzing elliptic cylindrical objects in a layered background. AB - The vertical mode expansion method (VMEM) [J. Opt. Soc. Am. A31, 293 (2014)] is a frequency-domain numerical method for solving Maxwell's equations in structures that are layered separately in a cylindrical region and its exterior. Based on expanding the electromagnetic field in one-dimensional vertical modes, the VMEM reduces the original three-dimensional problem to a two-dimensional (2D) problem on the vertical boundary of the cylindrical region. However, the VMEM has so far only been implemented for structures with circular cylindrical regions. In this paper, we develop a VMEM for structures with an elliptic cylindrical region, based on the separation of variables in the elliptic coordinates. A key step in the VMEM is to calculate the so-called Dirichlet-to-Neumann (DtN) maps for 2D Helmholtz equations inside or outside the ellipse. For numerical stability reasons, we avoid the analytic solutions of the Helmholtz equations in terms of the angular and radial Mathieu functions, and construct the DtN maps by a fully numerical method. To illustrate the new VMEM, we analyze the transmission of light through an elliptic aperture in a metallic film, and the scattering of light by elliptic gold cylinders on a substrate. PMID- 26366774 TI - Range resolved mode mixing in a large volume for the mitigation of speckle and strategic target orientation requirements in active millimeter-wave imaging. AB - In spite of many reports of active millimeter-wave imaging in the literature, speckle and requirements for cooperative target orientation significantly reduce its practical usefulness. Here we report a new technique, range resolved mode mixing (RRMM), which significantly mitigates both of these issues. It also provides a three-dimensional (3D) image. RRMM accomplishes this by combining multimode illumination (which eliminates the requirement for cooperative target orientation) with range resolution (which provides statistical independence of speckle patterns for averaging and the 3D image). The use of a 5W extended interaction klystron amplifier results in large signal margins in the 50 m scale atrium of the Physics Department at Ohio State University. It appears that there are a number of scenarios out to a range of 1 km for which this approach is useful to provide 3D images, with minimal speckle, and no requirement for cooperative target orientation. PMID- 26366775 TI - Free-space nonperpendicular electric-magnetic fields. AB - The electric and magnetic components of an electromagnetic wave in free space are believed by many to be perpendicular to each other. We outline a procedure by which electromagnetic potentials are constructed, and we derive free-space nonperpendicular electric-magnetic fields from these potentials. We show, for example, that in free-space Bessel-related fields, at a small region near the origin, the angle between these components spans a range of 7 degrees -173 degrees , that is, they are far from being perpendicular. This can be contrasted with plane waves, where, following the same procedure, we verify that the electric field strength (E(x,y,z,t)) and the magnetic flux density (B(x,y,z,t)) are indeed perpendicular to each other and to the direction of propagation. PMID- 26366776 TI - Analytical expression for the average ensquared energy. AB - We derive an expression for the average area of intersection between a blur spot of radius R and a square pixel, where the center of the blur is uniformly chosen from the pixel interior. Implications of the result are then discussed in the context of a point source detection problem. PMID- 26366777 TI - Poynting vector profile of a tightly focused radially polarized beam in the presence of primary aberrations. AB - The Poynting vector profile of a tightly focused radially polarized beam has some unique and interesting properties. For instance the light on the optical axis in the focal volume corresponds to a null Poynting vector, indicating the light there to be nonpropagating. However, the beam here is considered to be an unaberrated one. Thus it will be important to know whether the commonly occurring monochromatic aberrations can have any effect on the ideal Poynting vector profile of a radially polarized beam. In this paper we make use of the Fourier transform form of the vectorial diffraction theory to investigate the effect of primary aberrations on the Poynting vector profile of a radially polarized beam under tight focusing conditions. We present here the results from our study on the behavior of both the time averaged and time dependent Poynting vector profiles in the focal volume. PMID- 26366778 TI - Perturbative analysis of partially coherent illumination for coma aberration measurements. AB - The theory of coma aberration measurement for aerial image sidelobe peaks is extended from coherent illumination to partial illumination. We prove that the intensity difference between the two peaks is linear to the amount of coma aberration in the partially coherent case. Using weak diffraction approximation, we analytically reveal the coherence dependency of the aberration measurement sensitivity for a single line in a bright field. We confirm that our derived formulas are well matched with the numerical lithography simulation results. These results provide guidelines for the measurement condition; higher aberration sensitivity is available under the higher illumination pupil coherence. PMID- 26366779 TI - Generic propagation of beams with sharp spatial boundaries. AB - The propagation of spatial beams with initially sharp transverse boundaries is investigated theoretically and experimentally with the paraxial wave equation (PWE). The sharp boundaries generate a universal pattern, which is a consequence of the Schrodinger-like nature of the paraxial dynamics. As a consequence, an approximate analytical expression can be derived for the longitudinal propagation dynamics of the beam. Furthermore, it is shown that the validation of the derived analytical approximation is not limited to the zone in which the PWE is valid, but it is valid in the entire space. Therefore, this solution is a good approximation for the solution of the scalar wave equation (and to the Maxwell wave equation whenever the aperture is much wider than the wavelength of light) in the entire space. Good agreement between the analytical expression and experiment results is presented. PMID- 26366780 TI - Uniform asymptotics of paraxial boundary diffraction waves. AB - Starting from the paraxial formulation of the boundary-diffracted-wave theory proposed by Hannay [J. Mod. Opt. 47, 121-124 (2000)] and exploiting its intrinsic geometrical character, we rediscover some classical results of Fresnel diffraction theory, valid for "large" hard-edge apertures, within a somewhat unorthodox perspective. In this way, a geometrical interpretation of the Schwarzchild uniform asymptotics of the paraxially diffracted wavefield by circular apertures [K. Schwarzschild, Sitzb. Munchen Akad. Wiss. Math.-Phys. Kl. 28, 271-294 (1898)] is given and later generalized to deal with arbitrarily shaped apertures with smooth boundaries. A quantitative exploration is then carried out, with the language of catastrophe optics, about the diffraction patterns produced within the geometrical shadow by opaque elliptic disks under plane wave illumination. In particular, the role of the ellipse's evolute as a geometrical caustic of the diffraction pattern is emphasized through an intuitive interpretation of the underlying saddle coalescing mechanism, obtained by suitably visualizing the saddle topology changes induced by letting the observation point move along the ellipse's major axis. PMID- 26366781 TI - Experimental demonstration of a secondary source of partially polarized states. AB - We present a simple device that works as a secondary source of light with prescribed polarization properties. The device has great versatility, allowing complete control over both the degree of polarization and the Stokes vector that belongs to the fully polarized component of partially polarized light beams. We report experimental results that illustrate the device's versatility, by showing how polarized states can be moved within the Poincare ball along spiraling paths. PMID- 26366783 TI - Model Approach in Heterogeneous Catalysis: Kinetics and Thermodynamics of Surface Reactions. AB - Heterogeneous catalysts are widely employed in technological applications, such as chemical manufacturing, energy harvesting, conversion and storage, and environmental technology. Often they consist of disperse metal nanoparticles anchored onto a morphologically complex oxide support. The compositional and structural complexity of such nanosized systems offers many degrees of freedom for tuning their catalytic performance. However, a rational design of heterogeneous catalysts based on an atomistic-level understanding of underlying surface processes has not been fully achieved so far and remains one of the primary goals for catalysis research. In our group, we developed concepts for replacing highly complex real supported catalysts by simplified model systems, which complexity can be gradually increased in order to mimic certain structural aspects of practically relevant catalysts in a controlled way. Well-defined model systems consisting of metal-nanoparticle ensembles supported on planar oxide substrates have proven to provide a successful approach to achieve fundamental insights into heterogeneous catalysis. In this Account, two mechanistic case studies focusing on an atomistic-level understanding of surface chemistry are presented in which we investigate how the nanoscopic nature of metal clusters affects their interaction with the adsorbates and the reactive processes. Particularly, we investigate the effects of the particle size and the flexibility of the atoms constituting metal clusters on the binding energy of gas-phase adsorbates, such as CO and oxygen. We identified two major structural factors determining the binding energy of gas phase adsorbates on metal nanoparticles: the local configuration of the adsorption site and the particle size. While the effect of the local configuration of the adsorption site was found to be adsorbate specific, the reduction of the cluster size results in a pronounced decrease of binding energy for both adsorbates and appears to be a general trend. In the second case study, we address the role of the surface modifiers, such as carbon, on the process of hydrogen diffusion into volume of Pd nanoparticles that was previously identified is an important step in hydrogenation chemistry. We provide for the first time direct experimental evidence that, inline with the recent theoretical predictions, the atomically flexible low-coordinated surface sites on Pd particles play a crucial role in the diffusion process and that their selective modification with carbon results in marked facilitation of subsurface hydrogen diffusion. By virtue of these examples, we demonstrate how model studies on complex nanostructured materials may provide an atomistic view of processes at the gas-solid interface related to heterogeneous catalysis. PMID- 26366782 TI - Inhibition of phosphorylated tyrosine hydroxylase attenuates ethanol-induced hyperactivity in adult zebrafish (Danio rerio). AB - Zebrafish have been successfully employed in the study of the behavioural and biological effects of ethanol. Like in mammals, low to moderate doses of ethanol induce motor hyperactivity in zebrafish, an effect that has been attributed to the activation of the dopaminergic system. Acute ethanol exposure increases dopamine (DA) in the zebrafish brain, and it has been suggested that tyrosine hydroxylase, the rate-limiting enzyme of DA synthesis, may be activated in response to ethanol via phosphorylation. The current study employed tetrahydropapaveroline (THP), a selective inhibitor of phosphorylated tyrosine hydroxylase, for the first time, in zebrafish. We treated zebrafish with a THP dose that did not alter baseline motor responses to examine whether it can attenuate or abolish the effects of acute exposure to alcohol (ethanol) on motor activity, on levels of DA, and on levels of dopamine's metabolite 3,4 dihydroxyphenylacetic acid (DOPAC). We found that 60-minute exposure to 1% alcohol induced motor hyperactivity and an increase in brain DA. Both of these effects were attenuated by pre-treatment with THP. However, no differences in DOPAC levels were found among the treatment groups. These findings suggest that tyrosine hydroxylase is activated via phosphorylation to increase DA synthesis during alcohol exposure in zebrafish, and this partially mediates alcohol's locomotor stimulant effects. Future studies will investigate other potential candidates in the molecular pathway to further decipher the neurobiological mechanism that underlies the stimulatory properties of this popular psychoactive drug. PMID- 26366784 TI - A fluorescent cholesterol analogue for observation of free cholesterol in the plasma membrane of live cells. AB - Free cholesterol in mammalian cells resides mostly in the plasma membrane, where it plays an important role in cellular homeostasis. We synthesized a new fluorescent cholesterol analogue that retained an intact alkyl chain and the sterane backbone of cholesterol. The hydroxyl group of cholesterol was converted into an amino group that was covalently linked to the fluorophore tetramethylrhodamine to retain the ability to form hydrogen bonds with adjacent molecules. Incubating live MDCK (Madin-Darby canine kidney) cells with our fluorescent cholesterol analogue resulted in the generation of intense signals that were detected by microscopy at the plasma membrane. Incubation with the analogue exerted minimal, if any, influence on cell growth, indicating that it could serve as a useful tool for analyzing free cholesterol at the plasma membrane. PMID- 26366785 TI - High Prevalence of Low Bone Mineral Density and Substantial Bone Loss over 4 Years Among HIV-Infected Persons in the Era of Modern Antiretroviral Therapy. AB - HIV-infected persons are living longer on combination antiretroviral therapy (cART) but experiencing more comorbidities including low bone mineral density (BMD). Using data from the Study to Understand the Natural History of HIV and AIDS in the Era of Effective Therapy (SUN Study), we determined the prevalence of low BMD (T-score below one standard deviation of the reference mean) and compared it with matched controls from the National Health and Nutrition Examination Survey (NHANES). We also assessed 4-year longitudinal BMD changes among participants virologically suppressed on cART. Of 653 participants included in this analysis (77% male, 29% black, median age 41 years, median CD4(+) cell count 464 cells/mm(3), 89% with HIV RNA <400 copies/ml), 51% and 10% had baseline osteopenia and osteoporosis, respectively. Low BMD at the femoral neck was significantly more prevalent than for the NHANES controls (47% versus 29%, p<0.001). Lower body mass index, nonwhite race, longer tenofovir exposure, older age, being unemployed or retired, and lower apolipoprotein E were independently associated with baseline osteoporosis. Among 170 participants virologically suppressed on cART and with longitudinal BMD data, 31% experienced substantial bone loss (>=5% BMD decline from baseline) over 4 years. Female sex, current smoking, and longer stavudine use were more common among participants who had substantial bone loss, although these variables failed to reach statistical significance. Low BMD was highly prevalent among HIV-infected persons. One-third of participants experienced substantial bone loss despite cART, suggesting the need for monitoring and potential clinical interventions. PMID- 26366786 TI - Placental Villous Vascularity Is Decreased in Premature Infants with Bronchopulmonary Dysplasia-Associated Pulmonary Hypertension. AB - The development of pulmonary hypertension (PH) is a serious complication of bronchopulmonary dysplasia (BPD) among infants born at extremely low gestational ages. Bronchopulmonary dysplasia-associated PH is characterized by persistent pulmonary vasoconstriction, progressive right heart dysfunction, and an increased risk of death. We have shown previously that certain placental vascular lesions are associated with BPD-associated PH. Further evaluation of the villous and vascular morphometry of these placentas is warranted. Using digital image analysis (DIA), we compared villous and vascular morphometric parameters of placentas from infants with and without BPD-associated PH. We conducted a case control study of placentas from 14 infants born at <=28 weeks' gestational age (GA). Cases with PH (N=7) and non-PH controls (N=7) were identified using echocardiogram screening at 36 weeks' corrected GA. Central parenchymal sections from each placenta were stained for CD31. Digital image analysis was used to measure vessel and villous capillary number, perimeter, diameter, and area. Mean villous vascularity (number of vessels per villus) was calculated for each patient. Mean vessel and villous number as well as area were similar between the two groups. Villous vascularity was decreased in placentas from infants who ultimately had PH disease compared to non-PH controls (5.5+/-1.0 vs 7.1+/-1.6; P<0.05). Placental villous vascularity is decreased in infants with BPD associated PH. Further studies should assess whether placental morphometric markers may allow clinicians to better predict BPD and provide earlier and more targeted management. PMID- 26366787 TI - Factors influencing variation in physician adenoma detection rates: a theory based approach for performance improvement. AB - BACKGROUND AND AIMS: Interventions to improve physician adenoma detection rates for colonoscopy have generally not been successful, and there are little data on the factors contributing to variation that may be appropriate targets for intervention. We sought to identify factors that may influence variation in detection rates by using theory-based tools for understanding behavior. METHODS: We separately studied gastroenterologists and endoscopy nurses at 3 Kaiser Permanente Northern California medical centers to identify potentially modifiable factors relevant to physician adenoma detection rate variability by using structured group interviews (focus groups) and theory-based tools for understanding behavior and eliciting behavior change: the Capability, Opportunity, and Motivation behavior model; the Theoretical Domains Framework; and the Behavior Change Wheel. RESULTS: Nine factors potentially associated with adenoma detection rate variability were identified, including 6 related to capability (uncertainty about which types of polyps to remove, style of endoscopy team leadership, compromised ability to focus during an examination due to distractions, examination technique during withdrawal, difficulty detecting certain types of adenomas, and examiner fatigue and pain), 2 related to opportunity (perceived pressure due to the number of examinations expected per shift and social pressure to finish examinations before scheduled breaks or the end of a shift), and 1 related to motivation (valuing a meticulous examination as the top priority). Examples of potential intervention strategies are provided. CONCLUSIONS: By using theory-based tools, this study identified several novel and potentially modifiable factors relating to capability, opportunity, and motivation that may contribute to adenoma detection rate variability and be appropriate targets for future intervention trials. PMID- 26366788 TI - In search of key genes associated with endometriosis using bioinformatics approach. AB - OBJECTIVE: The aim of this study was to identify key genes associated with endometriosis. STUDY DESIGN: Microarray data GSE7846 was downloaded from Gene Expression Omnibus. The differentially expressed genes (DEGs) in human endometrial endothelial cells derived from eutopic endometrium of patients with endometriosis compared with controls without endometriosis were identified using Linear Models for Microarray Data (LIMMA) package in R. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and gene ontology (GO) enrichment analyses were performed using DAVID. Moreover, the protein-protein interaction (PPI) network was constructed by STRING and subsequently significantly enriched modules were mined by ClusterONE. Finally, protein domains and KEGG pathway enrichment analyses were performed for PPI modules. RESULTS: A total of 687 DEGs were identified, including 584 up- and 103 down-regulated genes. The up-regulated DEGs, such as epidermal growth factor (EGF) and interleukin 1 beta (IL-1beta) were significantly enriched in KEGG pathways of focal adhesion, ECM-receptor interaction and calcium signaling pathway. Similarly, only one module was obtained form PPI network, and the genes, like angiotensin II receptor, Type 1 (AGTR1) in the module were mainly enriched in protein domain of rhodopsin-like G protein-coupled receptors and most altered pathways of neuroactive ligand receptor interaction, calcium signaling pathway and vascular smooth muscle contraction. CONCLUSIONS: Our findings indicate that EGF, IL-1beta and AGTR1 may play important roles in the pathogenesis of endometriosis. PMID- 26366789 TI - Cesarean analgesia using levobupivacaine continuous wound infiltration: a randomized trial. AB - OBJECTIVE: Neuraxial morphine is considered as a "gold standard" for pain relief after cesarean section, however it causes bothersome side effects. Alternative analgesia including nonsteroidal antiinflammatory drugs (NSAID) has been proposed. We aimed to assess the morphine sparing effect of continuous wound infiltration with a local anesthetic, when added to multimodal systemic analgesia including NSAID without subarachnoid morphine. STUDY DESIGN: Sixty-eight women scheduled for elective cesarean section under spinal anesthesia were included in a randomized controlled open-label trial. Patients received bupivacaine spinal anesthesia without intrathecal morphine. Postoperative analgesia consisted for all patients in multimodal systemic analgesia with acetaminophen, nefopam, celecoxib, and patient-controlled intravenous morphine for 24h. The intervention group also received subfascial levobupivacaine infiltration through a multi-holed catheter, at 6.25mg/h for 48h. The primary endpoint was total morphine consumption at 24h postoperatively; and secondary endpoints were pain scores, side effects, breastfeeding comfort, maternal satisfaction, and nurse workload. Student t test, Mann-Whitney test or chi(2) test were used when appropriate. RESULTS: The intervention group had 6.7mg less morphine consumption (95%CI 1.3mg; -12mg, P=0.02), and 0.8 pain point less at rest on the numerical rating scale 0-10 (95%CI -0.3; -1.3, P=0.002). The intervention was associated with significantly better breastfeeding comfort (+1.7 at numerical rating scale score 0-10, 95%CI +0; +3.3, P=0.0498). Wound dressing changes were required in a significantly higher proportion of intervention-group women (12/34 vs. 1/34, P=0.002). CONCLUSION: Adding continuous levobupivacaine infiltration to multimodal analgesia after cesarean section without subarachnoid morphine decreased postoperative morphine consumption and pain, facilitated breastfeeding initial comfort, and slightly increased nurse workload. PMID- 26366790 TI - Embryo quality is the main factor affecting cumulative live birth rate after elective single embryo transfer in fresh stimulation cycles. AB - OBJECTIVE: The study was aimed to evaluate which factors affect the cumulative live birth rate after elective single embryo transfer in women younger than 36 years. Additionally, number of children in women with more than one delivery per ovum pick-up after fresh elective single embryo transfer and subsequent frozen embryo transfers was assessed. STUDY DESIGN: Retrospective cohort study analysing data of a university hospital's infertility clinic in 2001-2010. A total of 739 IVF/ICSI cycles with elective single embryo transfer were included. Analyses were made per ovum pick-up including fresh and subsequent frozen embryo transfers. Factors affecting cumulative live birth rates were examined in uni- and multivariate analyses. A secondary endpoint was the number of children born after all treatments. RESULTS: In the fresh cycles, the live birth rate was 29.2% and the cumulative live birth rate was 51.3%, with a twin rate of 3.4%. In the multivariate analysis, having two (odds ratio (OR) 1.73; 95% confidence interval (CI) 1.12-2.67) or >=3 top embryos (OR 2.66; 95% CI 1.79-3.95) was associated with higher odds for live birth after fresh and frozen embryo cycles. Age, body mass index, duration of infertility, diagnosis or total gonadotropin dose were not associated with the cumulative live birth rate. In cycles with one top embryo, the cumulative live birth rate was 40.2%, whereas it was 64.1% in those with at least three top embryos. Of women who had a live birth in the fresh cycle, 20.4% had more than one child after all frozen embryo transfers. Among women with three or more top embryos after ovum pick-up, 16.1% gave birth to more than one child. CONCLUSION: The cumulative live birth rate in this age group varies from 40% to 64% and is dependent on the quality of embryos. Women with three or more top embryos have good chance of having more than one child per ovum pick-up without elevated risk of multiple pregnancies. PMID- 26366792 TI - Erbium laser in gynecology: aims, aspirations and action points. PMID- 26366793 TI - Erbium laser in gynecology. AB - The aim of this paper is to present a novel laser technology utilizing the erbium YAG laser for various minimally invasive, non-surgical procedures in gynecology. Non-ablative, thermal-only SMOOTH-mode erbium pulses are used to produce vaginal collagen hyperthermia, followed by collagen remodeling and the synthesis of new collagen fibers, resulting in improved vaginal tissue tightness and elasticity. This erbium laser technology is used for treatments of vaginal laxity, stress urinary incontinence, pelvic organ prolapse and vaginal atrophy. In the period from 2010 to 2014, several clinical studies covering all four indications were conducted with the aim to prove the efficacy and safety of this novel technology. An overview is presented of the results of these studies where several objective as well as subjective assessment tools were used. The results have shown that SMOOTH-mode erbium laser seems to be an effective and safe method for treating vaginal laxity, stress urinary incontinence, pelvic organ prolapses and vaginal atrophy. PMID- 26366794 TI - Vaginal biological and sexual health--the unmet needs. AB - The vagina is a most neglected organ. It is usually clinically considered with a minimalistic view, as a 'connecting tube' for a number of physiologic functions: passage of menstrual blood, intercourse, natural conception and delivery. Unmet needs include, but are not limited to, respect of vaginal physiologic biofilms; diagnosis and care of the optimal tone of the levator ani, which surrounds and partly support it; care of its anatomic integrity at and after delivery and at pelvic/vaginal surgery; care of long-term consequences of pelvic radiotherapy; long-term care of the atrophic changes it will undergo after the menopause, unless appropriate, at least local, estrogen therapy is used; appreciation and respect of its erotic meaning, as a loving, receptive, 'bonding' organ for the couple. The vaginal erotic value is key as a non-visible powerful center of femininity and sexuality, deeply and secretly attractive in terms of taste, scent (together with the vulva), touch and proprioception. The most welcoming when lubrication, softness and vaginal orgasm award the woman and the partner with the best of pleasures. Prevention of sexual/vaginal abuse is a very neglected unmet need, as well. Who cares? PMID- 26366791 TI - Comparison of customized and cohort-based birthweight standards in identification of growth-restricted infants in GUSTO cohort study. AB - BACKGROUND: The aim was to evaluate the ability of customized and cohort birthweight standards in discriminating intrauterine growth retardation (IUGR). METHODS: Birthweights (BWs) of GUSTO singleton infants born at gestational age (GA) 35-41 weeks were converted using two standards: (a) GUSTO cohort-based BW centile adjusted for GA and baby gender; (b) customized BW percentile calculator adjusted for maternal height and weight, race, parity, GA and gender. Infants were classified into three groups: (1) < 10th BW centile by customization- customized-SGA, (2) < 10th BW centile by GUSTO- GUSTO-SGA; and (3) > 10th BW centile by both standards - BOTH-non-SGA. RESULTS: Of the 1011 infant-mother dyads, 68 were customized-SGA and 104 were GUSTO-SGA, with concordance of 61% (n = 63) for SGA. While 5 (7%) of customized-SGA were not SGA by GUSTO-charts, 41 (39%) of GUSTO-SGA were not SGA by customized-charts. Customized-SGA had significantly the least growth in abdominal circumference (AC) and highest head circumference (HC): AC growth ratio between second and third trimester; and the lowest mean BW, ponderal index and placental weight than other groups. CONCLUSION: Customized-SGA standard was a better discriminator of pathologic fetal growth based on AC growth. It improved strength of association with pathology and in our population reduced false positives (41/104 = 39%) in the assessment of SGA. PMID- 26366795 TI - Genitourinary syndrome of the menopause--dawn of a new era? AB - Many millions of postmenopausal women continue to suffer in silence from symptoms resulting from estrogen-deficient atrophy of the vulva, vagina and urinary tract whilst the medical profession continues to debate what the condition should be called, how it should be assessed and whether it should be universally treated. It is high time that a unified approach was adopted by all medical societies to reach a consensus on definitions, recognition and management. With the development of the nomenclature for genitourinary syndrome of the menopause (GSM), advances in GSM assessment tools and quality-of-life questionnaires and novel therapeutic interventions, the signs are positive that a new era is finally dawning. PMID- 26366796 TI - The urogenital system and the menopause. AB - The major cause of urogenital atrophy in menopausal women is estrogen loss. The symptoms are usually progressive in nature and deteriorate with time from the menopausal transition. The most prevalent urogenital symptoms are vaginal dryness, vaginal irritation and itching. The genitourinary syndrome of menopause includes vulvovaginal atrophy and the postmenopausal modifications of the lower urinary tract. Dyspareunia and vaginal bleeding from fragile atrophic skin are common problems. Other urogenital complaints include frequency, nocturia, urgency, stress urinary incontinence and urinary tract infections. Atrophic changes of the vulva, vagina and lower urinary tract can have a large impact on the quality of life of the menopausal woman. However, hormonal and non-hormonal treatments can provide patients with the solution to regain the previous level of function. Therefore, clinicians should sensitively question and examine menopausal women, in order to correctly identify the pattern of changes in urogenital atrophy and manage them appropriately. PMID- 26366797 TI - Treatment of the genitourinary syndrome of menopause. AB - The vagina, vulva, vestibule, labia majora/minora, and bladder trigone have a high concentration of estrogen receptors; therefore, they are a sensitive biological indicator of serum levels of these hormones in women. The estrogen loss in postmenopausal women produces a dysfunction called genitourinary syndrome of menopause. The principal therapeutic goal in the genitourinary syndrome of menopause is to relieve symptoms. Treatment options, as well as local and systemic hormonal treatment are changes in lifestyle and non-hormonal treatments mainly based on the use of moisturizers and lubricants. New treatments that have recently appeared are ospemifeme, the first selective hormone receptor modulator for dyspareunia and vulvovaginal atrophy treatment, and the use of vaginal laser. This review has been written with the intention of giving recommendations on the prevention and treatment of genitourinary syndrome of menopause. PMID- 26366798 TI - Female urinary stress incontinence. AB - Urinary incontinence (UI) is more common than any other chronic disease, such as hypertension, depression or diabetes, with the prevalence estimated between 9 and 74%. Among the various forms of urinary incontinence, stress incontinence (SUI) is the most prevalent (50%), with urgency incontinence (UUI) representing 11% and mixed type (MUI) 36% (3% not classified). Nowadays, the restoration of urinary continence is one of the greatest challenges for the well-being and quality of life of women. The introduction of minimally invasive surgical procedures changed the anti-incontinence surgery, leading to similar, or even better results as traditional, invasive techniques. The development of the mid-urethral slings offers a viable alternative to surgical correction of SUI. These further developments of mini-sling procedures are appropriate for local anesthesia, less traumatic, 'tension-free' (to ensure continence without obstruction), simple, rapid and repeatable. The latest minimally invasive approaches can be performed in day surgery, with clear advantages compared to traditional procedures. A novel approach through the use of vaginal laser techniques could represent an additional opportunity, as a non-invasive, outpatient method to treat SUI. PMID- 26366799 TI - First assessment of short-term efficacy of Er:YAG laser treatment on stress urinary incontinence in women: prospective cohort study. AB - OBJECTIVES: This is the first assessment of efficacy and safety of the Er:YAG laser in the treatment of stress urinary incontinence. The aim of this study was to assess the short-term outcome of a non-invasive laser treatment for mild-to severe stages of this condition and to check its applicability in different body mass index and age groups. METHODS: A prospective cohort, single-center study at the Ob/Gyn Clinic, Zagreb, Croatia recruited a consecutive sample of 73 female patients suffering from stress urinary incontinence. The procedure was performed with a 2940-nm Er:YAG laser (XS Dynamis, Fotona, Slovenia) designed to achieve heating up of vaginal mucosa to around 60 degrees C, 500-700 MUm in depth. RESULTS: The score in the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form was reduced to a median of 46% (95% confidence interval 33-67%; p < 0.001). The reduction was significantly higher in women with normal body mass index (67%) than in overweight women (25%), as well as in women younger than 39 years (100%) compared with those older than 60 years (8%) (p < 0.001). No serious adverse events were noticed. CONCLUSION: This study of Er:YAG laser therapy in women has demonstrated a clinically relevant, short term improvement of stress urinary incontinence, with minimal adverse events of a transient nature. PMID- 26366800 TI - Rationale and design for the Vaginal Erbium Laser Academy Study (VELAS): an international multicenter observational study on genitourinary syndrome of menopause and stress urinary incontinence. AB - The genitourinary syndrome of menopause (GSM) and stress urinary incontinence (SUI) are common clinical challenges for women's health and quality of life. The laser treatment and particularly the vaginal erbium laser (VEL) may provide a new non-invasive treatment for both GSM and SUI. However, the estimation of the ultimate results of different laser treatments may be altered by different issues, such as patient selection, concomitant treatments, and long-term effect of vaginal laser thermotherapy. In the present paper, we present the protocol for a large multicenter study on the evaluation of the efficacy and safety of VEL for the treatment of GSM and SUI, the Vaginal Erbium Laser Academy Study (VELAS). This study will evaluate the effects of three laser applications in 1500 postmenopausal women. Subjective and objective symptoms will be evaluated prior to the first laser treatment with follow-up visits after 4 weeks from the last laser application, and subsequently after every 3 months for 1 year. Findings from the VELAS have the potential to affect clinical care practice and health decisions for millions of women world-wide for a non-hormonal treatment for GSM and a non-invasive treatment of SUI. PMID- 26366801 TI - Meat Authentication via Multiple Reaction Monitoring Mass Spectrometry of Myoglobin Peptides. AB - A rapid multiple reaction monitoring (MRM) mass spectrometric method for the detection and relative quantitation of the adulteration of meat with that of an undeclared species is presented. Our approach uses corresponding proteins from the different species under investigation and corresponding peptides from those proteins, or CPCP. Selected peptide markers can be used for species detection. The use of ratios of MRM transition peak areas for corresponding peptides is proposed for relative quantitation. The approach is introduced by use of myoglobin from four meats: beef, pork, horse and lamb. Focusing in the present work on species identification, by use of predictive tools, we determine peptide markers that allow the identification of all four meats and detection of one meat added to another at levels of 1% (w/w). Candidate corresponding peptide pairs to be used for the relative quantification of one meat added to another have been observed. Preliminary quantitation data presented here are encouraging. PMID- 26366802 TI - Pharmacogenetic tests to predict the efficacy of aspirin desensitization in patients with aspirin-exacerbated respiratory diseases; HLA-DQB302. AB - This study is aimed at investigating the association of HLA-DRB1, HLA-DQA1, and HLA-DQB1 variability with the response to aspirin desensitization (AD). A total of 16 patients with aspirin-exacerbated respiratory diseases (AERD, 81.3% were female) with median age of 29 +/- 4.3 years were included in this study. Following 6 months, Sino-Nasal Outcome Test-22 (SNOT-22), medication, symptom scores, and forced expiratory volume in 1 s (FEV1) (all p < 0.001) improved significantly. However, only seven patients (43.7%) had clinically significant improvement in all of the medication and symptom scores and FEV1, who were considered responders to AD. Responders to AD had significantly higher symptom scores compared with non-responders at baseline (20 +/- 1.18 vs 10 +/- 1.27; p = 0.003). HLADQB1*0302 was significantly lower in non-responders than in responders to AD (0.12 [0.02-0.76]; p = 0.022). Sensitivity and specificity of HLA-DQB1*0302 to predict response to AD was 71.4% (95% CI: 35.8-91.7) and 81.8% (95% CI: 52.3 94.8). This study introduces HLA-DQB1*0302 as a genetic marker for favorable response to AD. PMID- 26366803 TI - Dual bronchodilator therapy with aclidinium bromide/formoterol fumarate for chronic obstructive pulmonary disease. AB - Inhaled bronchodilator therapy is a mainstay of treatment for chronic obstructive pulmonary disease (COPD). Despite the number and types of treatments available, the control of symptoms and exacerbations remains suboptimal, and adherence to, and persistence with, inhaled therapy is generally poor. Results from clinical studies suggest that dual bronchodilator therapy with long-acting muscarinic receptor antagonists (LAMAs) and long-acting beta2 adrenergic receptor agonists (LABAs) may provide additional benefit over LAMA or LABA monotherapy without additive effects on safety and tolerability. Several combinations of a LAMA plus a LABA have recently become available in a single inhaler for maintenance therapy for adults with moderate-to-severe COPD, including aclidinium bromide/formoterol fumarate, glycopyrronium/indacaterol and umeclidinium/vilanterol. Here, we review clinical data demonstrating significant improvements in bronchodilation, 24-h symptoms, and health status with aclidinium/formoterol twice daily, and discuss how this treatment can be implemented in clinical practice as part of a patient focused approach to disease control. PMID- 26366804 TI - Systemic therapy options for malignant pleural mesothelioma beyond first-line therapy: a systematic review. AB - The aim of this systematic review is to assess the evidence for the available 2nd/3rd line systemic therapies for malignant pleural mesothelioma (MPM). Eligible studies were obtained through appropriate databases and meetings abstracts search. A total of 29 studies were considered eligible for this review and it includes three Phase III studies, eighteen phase II studies and eight retrospective studies. For the Phase III studies, none have achieved an overall survival benefit; while for the Phase II studies, the majority have not achieved sufficient satisfactory outcome to justify advancement to Phase III studies. We believe that the best salvage treatment for MPM would be inclusion into appropriately designed clinical trials. In the absence of a clinical trial, gemcitabine and/or vinorelbine-based regimens could be considered. Moreover, pemetrexed re-challenge can be considered in selected pemetrexed-sensitive patients. PMID- 26366805 TI - Developments in pulmonary arterial hypertension-targeted therapy for chronic thromboembolic pulmonary hypertension. AB - Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare disease characterised by the presence of organised chronic thromboembolic material occluding the proximal pulmonary arteries and a vasculopathy in the distal pulmonary arterial tree. Pulmonary endarterectomy (PEA) is a potential cure for many patients with CTEPH. However, PEA is not suitable for patients with a significant distal distribution of chronic thromboembolic material or with significant comorbidities. Also, a proportion of patients are left with residual CTEPH post PEA. Until recently, pulmonary arterial hypertension-targeted therapies have been used off licence to treat patients with inoperable or residual CTEPH. The CHEST1 study investigated the use of riociguat and was the first randomised controlled trial to show efficacy in inoperable or residual CTEPH. In this review, we explore the pathophysiology of CTEPH and review the current trial evidence for pulmonary arterial hypertension-targeted therapies. We also include a discussion of physiological considerations that require further investigation. PMID- 26366806 TI - Management of patients with respiratory infections in primary care: procalcitonin, C-reactive protein or both? AB - Use of inflammatory biomarkers to guide antibiotic decisions has shown promising results in the risk-adapted management of respiratory tract infections, mainly in the inpatient setting. Several observational and interventional trials have investigated the benefits of procalcitonin (PCT) and C-reactive protein (CRP) testing in primary care. Both markers have shown promising results, although CRP is an inflammatory biomarker while PCT is more specific for bacterial infections. For CRP, point-of-care testing is widely established. Recently, sensitive point of-care testing for PCT has also become available. A high-quality trial comparing these two markers for the management of patients in primary care is currently lacking. The aim of this paper is to review the existing literature investigating the use of PCT and CRP in primary care. The authors compare their performance for guiding antibiotic stewardship and analyze the cut-off values and endpoints to put these parameters into context in a low-acuity environment. PMID- 26366807 TI - Newborn screening for cystic fibrosis. AB - Newborn screening for cystic fibrosis (CF NBS) has been introduced in almost all of the Western countries, and most of the children with CF are now being identified via CF NBS before disease-related symptoms develop. This review summarizes the evidence that has been generated to date to support the benefit of CF NBS and the various screening algorithms that are used in different jurisdictions. A special focus is directed towards the challenges arising from false-negative and -positive screening results. Finally, we review the emerging data reporting on positively-screened newborns, in whom confirmatory sweat testing resulted in an inconclusive diagnosis for CF. PMID- 26366808 TI - The etiology and therapy of primary spontaneous pneumothoraces. AB - Primary spontaneous pneumothorax (PSP) remains a significant health problem in young adults. Subpleural blebs and bullae in the lung apices are likely to play important roles in pathogenesis. The optimal management of PSP has been a matter of debate and depends on the size of the pneumothorax, the symptoms and the time of occurrence. Observation or simple aspiration is used in the first episode, while surgery is recommended for recurrent or complicated pneumothorax. Recent advances in thoracoscopic surgery have provided a less invasive alternative in the surgical treatment of PSP, but there are concerns about higher recurrence rates than that following open thoracotomy. Studies have shown that the judicious use of chemical pleurodesis may decrease the rate of recurrence in surgical and nonsurgical patients. In this article, the etiology and pathophysiology of PSP are reviewed. The indications, safety and effects of currently available treatment modalities are also summarized. PMID- 26366809 TI - Effectiveness of gamma-oryzanol in reducing neuromotor deficits, dopamine depletion and oxidative stress in a Drosophila melanogaster model of Parkinson's disease induced by rotenone. AB - The gamma-orizanol present in rice bran oil contains a mix of steryl triterpenyl esters of ferulic acid, which is believed to be linked to its antioxidant potential. In this study we investigated the neuroprotective actions of gamma orizanol (ORY) against the toxicity induced by rotenone (ROT) in Drosophila melanogaster. The flies (both genders) aged between 1 and 5 days old were divided into four groups of 50 flies each: (1) control, (2) ORY 25 MUM, (3) ROT 500 MUM, (4) ORY 25 MUM+ROT 500 MUM. Flies were concomitantly exposed to a diet containing ROT and ORY for 7 days according to their respective groups. Survival and behavior analyses were carried out in vivo, and ex vivo analyses involved acetylcholinesterase activity (AChE), determination of dopaminergic levels, cellular viability and mitochondrial viability, activities of superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), reactive species levels (RS), lipid peroxidation (TBARS) and contents of total thiols and non-proteic thiols (NPSH). Our results show for the first time that ORY not only acts as an endogenous activator of the cellular antioxidant defenses, but it also ameliorates rotenone induced mortality, oxidative stress and mitochondrial dysfunction. Our salient findings regarded the restoration of cholinergic deficits, dopamine levels and improved motor function provided by ORY. These results demonstrate the neuroprotective potential of ORY and that this effect can be potentially due to its antioxidant action. In conclusion, the present results show that ORY is effective in reducing the ROT induced toxicity in D. melanogaster, which showed a neuroprotective action, possibly due to the presence of the antioxidant constituents such as the ferulic acid. PMID- 26366810 TI - Intra-specific competition in predator can promote the coexistence of an eco epidemiological model with strong Allee effects in prey. AB - An eco-epidemiological model with Allee effects and disease in prey has been proposed and analyzed. The proposed model incorporates intra-specific competition in predator due to the limited food source, and assumes standard incidence disease transmission. We analyzed the corresponding submodels with and without the Allee effects to obtain the complete dynamics of the full model. Our results show that our full model shows multi-stability between the planner equilibriums (where the susceptible prey co-exists with infected prey or predator); both the full model and its submodels exhibit the hydra effects caused by the intra specific competition in predator. We determined the existence of multiple interior attractors and their stability. Our analysis shows that our system has at most two interior equilibria whose stability is either both saddle or one stable with another one saddle. One of the most interesting findings is that the competition in the predator can promote the coexistence of all the three populations. In addition, we discussed how the frequency-dependent transmission differs from the model with the density-dependent transmission and compare the hydra effects observed in our model to other existing models in literature. PMID- 26366812 TI - Melamine induces autophagy in mesangial cells via enhancing ROS level. AB - CONTEXT: Melamine, as an industrial chemical, was blended illegally with infant formula to counterfeit the illusion of more abundant protein content in 2008. Due to its nephrotoxicity, thousands of children underwent kidney disease. OBJECTIVE: It was to investigate whether melamine could affect autophagy in mesangial cells (MCs) via oxidative stress and whether autophagy played a positive role in protecting MCs impaired by melamine. MATERIALS AND METHODS: MCs were used as a mesangium model. The cell viability was measured by MTT assay. Intracellular hydrogen peroxide (H2O2) was assessed by using H2O2 assay kit. The Western blot assay was employed to measure the expression of autophagy-related proteins. RESULTS: MTT assay showed that melamine induced MCs death in a concentration dependent and time-dependent manner. The measurement of H2O2 demonstrated that melamine decreases H2O2 level of MCs. Meaningfully, treatment of a type of ROS scavenger formulation named N-(mercaptopropionyl)-glycine (N-MPG) could inhibit MCs death induced by melamine. Meanwhile, Western blot analysis indicated that melamine enhanced the ratio of LC3-II/LC3-I and Beclin-1 level in MCs, and N-MPG down-regulated autophagy in melamine-treated MCs. The cell viability of MCs with melamine and an autophagy inhibitor named 3-methyladenine (3-MA) showed that autophagy could protect melamine-treated MCs. CONCLUSIONS: The study showed that melamine-enhanced autophagy by increasing ROS levels in MCs, and autophagy could protect melamine-treated MCs. Improving autophagy may become a new potential clinical application to relieve melamine-induced renal injury. PMID- 26366813 TI - Uterine Full Thickness Multifocal Dehiscence Associated With a History of Cho Uterine Compression Sutures. PMID- 26366814 TI - It's Only Natural. PMID- 26366811 TI - Regulatory RNAs and control of epigenetic mechanisms: expectations for cognition and cognitive dysfunction. AB - The diverse functions of noncoding RNAs (ncRNAs) can influence virtually every aspect of the transcriptional process including epigenetic regulation of genes. In the CNS, regulatory RNA networks and epigenetic mechanisms have broad relevance to gene transcription changes involved in long-term memory formation and cognition. Thus, it is becoming increasingly clear that multiple classes of ncRNAs impact neuronal development, neuroplasticity, and cognition. Currently, a large gap exists in our knowledge of how ncRNAs facilitate epigenetic processes, and how this phenomenon affects cognitive function. In this review, we discuss recent findings highlighting a provocative role for ncRNAs including lncRNAs and piRNAs in the control of epigenetic mechanisms involved in cognitive function. Furthermore, we discuss the putative roles for these ncRNAs in cognitive disorders such as schizophrenia and Alzheimer's disease. PMID- 26366815 TI - Learning From Experience: Development of a Cognitive Task List to Perform a Safe and Successful Non-Rotational Forceps Delivery. AB - OBJECTIVE: Increased rates of delivery by Caesarean section have resulted in a reduction in rates of instrumental deliveries. This has led to a new educational challenge for teaching and development of skills. In teaching trainees, there are subconscious tasks that the supervising staff may not review because they are automatic. This study aimed to create a new tool to meet this challenge: to identify the core steps required to perform a non-rotational forceps delivery safely and successfully. METHODS: Labour and delivery nursing staff of three large teaching hospitals were asked to identify clinicians they considered to be particularly skilled in non-rotational forceps deliveries. Obstetricians who were identified consistently in this way were invited to participate in the study. After providing written consent, participants were then filmed performing a non rotational forceps delivery on a model. Two clinicians reviewed all videos and documented verbal and non-verbal components of the assessment. Thematic analysis combined findings into an integrated summary. The initial summary was then circulated to all participants for their approval. RESULTS: Seventeen clinicians were identified and consented. Themes identified included the need for careful assessment of suitability for operative delivery, the role of the multidisciplinary team, the need for careful and appropriate communication with the parents, the technique of delivery itself, and postpartum care and documentation. CONCLUSION: In the core steps identified, the clinicians balanced respect for the "elegant technique" of non-rotational forceps deliveries with careful assessment and knowing when to stop if safety criteria were not met. PMID- 26366816 TI - Relationship Between Interpregnancy Interval and Adverse Perinatal and Neonatal Outcomes in Northern Alberta. AB - BACKGROUND: Birth outcomes are known to be associated with birth spacing, but there are population differences. The purpose of this study was to examine the association between interpregnancy intervals and perinatal and neonatal outcomes in a Canadian population during the era of mandatory folate fortification of food. METHODS: We conducted a study of 46 243 women who had two consecutive singleton births in northern Alberta between 1999 and 2007, using a linked provincial dataset. Perinatal outcomes of interest were preterm birth, low birth weight (LBW), small for gestational age, and perinatal death. Neonatal outcomes were low Apgar score, low arterial blood gas pH, need for neonatal resuscitation or admission to NICU, and neonatal death. Multivariable logistic regression was used to control for maternal demographic and obstetrical characteristics. RESULTS: The risk of preterm birth was increased for multiple interpregnancy intervals: for an interval of 0 to 5 months, the adjusted odds ratio (aOR) was 1.37 (95% CI 1.18 to 1.59), for 6 to 11 months the aOR was 1.18 (95% CI 1.04 to 1.34), for 24 to 35 months the aOR was 1.16 (95% CI 1.02 to 1.31), and for 36+ months the aOR was 1.36 (95% CI 1.20 to 1.53), compared with the reference interval of 12 to 17 months. The risk of LBW was increased with interpregnancy intervals of 0 to 5 months (aOR 1.48; 95% CI 1.23 to 1.80), 6 to 11 months (aOR 1.21; 95% CI 1.03 to 1.42), 24 to 35 months (aOR 1.21; 95% CI 1.03 to 1.41) and 36+ months (aOR 1.48; 95% CI 1.27 to 1.73). The risk of SGA was increased with intervals 0 to 5 months (aOR 1.29; 95% CI 1.09 to 1.52), 24 to 35 months (aOR 1.15; 95% CI 1.01 to 1.31), and 36+ months (aOR 1.26; 95% CI 1.11 to 1.44). The risk of perinatal death was increased with an interval of 36+ months (aOR 1.60; 95% CI 1.06 to 2.43). Similar associations were also observed for neonatal outcomes. CONCLUSION: This study suggests that both short and long interpregnancy intervals are associated with adverse perinatal and neonatal outcomes, and it provides risk estimates for a Canadian population in the era of folate fortification of food. PMID- 26366817 TI - Barriers and Misperceptions Limiting Widespread Use of Intrauterine Contraception Among Canadian Women. AB - Unintended pregnancy is a major social and public health problem with adverse effects on neonatal and developmental outcomes, as well as maternal health and wellbeing. Traditionally, family planning policies have focused on increasing contraceptive uptake in non-users; however, rates of non-use are low in many developed nations. A high proportion of unintended pregnancies are attributable to contraceptive failure, particularly when using barrier and short-acting hormonal contraceptives. Intrauterine contraceptive devices (IUCDs) are highly effective and have been shown to reduce unintended pregnancy rates. Despite this, global utilization rates are low, and IUCD uptake in Canada has been particularly low. In this review we explore why IUCDs are not more widely used, and specifically focus on barriers and misperceptions that may influence IUCD uptake, particularly in Canada. We reviewed relevant articles published in English between 1990 and 2014, through searches of PubMed and Medline, including primary studies of any design containing information on the knowledge and attitudes of health care providers and women. Providing education to care providers, women, and policy makers may help overcome misperceptions about the use of IUCDs, and may facilitate greater use. Increased support from federal and provincial health programs may also encourage the use of IUCDs in Canadian women, and help to reduce unintended pregnancy rates. PMID- 26366818 TI - Effect of Menstrual Age on Failure of Medical Management in Women With Early Pregnancy Loss. AB - OBJECTIVE: Women with failure of an early pregnancy and a gestational age of <8 weeks are considered good candidates for medical management. The purpose of our study was to evaluate the effect of menstrual age on the outcome of medical management in women with loss of a pregnancy at an estimated gestational age<8 weeks by ultrasound (US). METHODS: We conducted a retrospective cohort study of all women discharged from the emergency department (ED) between 2011 and 2013 with a diagnosis of early pregnancy failure who were managed with misoprostol and who had a gestational age of <8 weeks on US. We used logistic regression to estimate the effect of menstrual age on failed medical management, defined as requiring dilatation and curettage (D and C) or having an unplanned return to the ED (URED). RESULTS: Among 823 pregnant women presenting to the ED with first trimester bleeding, 199 had pregnancy failure at <8 weeks by US and were discharged to use misoprostol. Increasing menstrual age was associated with an increased risk of D and C and URED. Specifically, the risk of D and C was 11.8% at <8 weeks, 18.5% at 8 to 9 weeks, 25.3% at 10 to 11 weeks, and 30.6% at >=12 weeks (P<0.05). The risk of URED was 14.7% at <8 weeks, 27.8% at 8 to 9 weeks, 36.0% at 10 to 11 weeks, and 41.7% at >=12 weeks (P<0.05). CONCLUSION: Increasing gestational age according to menstrual dates is associated with an increased rate of failed medical management in women with early pregnancy loss, independent of gestational age estimated by ultrasound. Gestational age by menstrual dates should be considered when discussing treatment options with women who have an early pregnancy failure. PMID- 26366819 TI - Adenoma Malignum Presenting With Profound Hyponatremia. AB - BACKGROUND: Adenoma malignum of the cervix (also referred to as minimal deviation adenocarcinoma) is a rare malignancy. Although previous reports have described adenoma malignum presenting with mucinous vaginal discharge, no reports to our knowledge have described a presentation with profound hyponatremia due to fluid losses. CASE: We present a case of adenoma malignum in a 52-year-old woman who presented with substantial watery vaginal discharge and profound hyponatremia. CONCLUSION: Despite being a rare cervical tumour, adenoma malignum should be considered in the differential diagnosis of watery vaginal discharge. This tumour can present with severe electrolyte disturbances. PMID- 26366820 TI - The Significance of Cutaneous Allodynia in a Woman With Chronic Pelvic Pain. AB - BACKGROUND: This is a case report of sensory assessment in a woman with severe chronic pelvic pain following uterine artery embolization, and a discussion of a commonly observed sensory manifestation (allodynia) associated with chronic pelvic pain due to gynaecological conditions. Allodynia, as a common sensory abnormality can be readily detected at the bedside and represents the development of pain sensitization. Emergence of abdominal and perineal allodynia (assessed by cotton swap stroking and/or questionnaire) is associated with the development of the clinical features of sensitization: continuous pelvic pain, muscle tenderness, and reduced pressure pain thresholds. CASE: A uterine artery embolization was performed on a 42-year-old woman to treat a postpartum hemorrhage. The woman experienced severe pain immediately following the procedure, and it had persisted for one year when she was referred for chronic unrelenting pain. She was found to have extensive allodynia, myofascial dysfunction, and reduced pain thresholds. A hysterectomy was undertaken. As the pain persisted, botulinum toxin was administered to the lower abdomen in the region of reduced pain thresholds. Partial resolution of pain, physical limitation, and allodynia resolved one year after the hysterectomy and shortly after the injections of four tender regions of the anterior cutaneous nerves with 2.5 and 5.0 IU of botulinum toxin. CONCLUSION: Testing for allodynia is a validated bedside test for pain sensitization. A clinical trial of botulinum toxin is indicated for the management of chronic pelvic pain associated with allodynia and pain sensitization. PMID- 26366821 TI - Experiencing Health Advocacy During Cervical Cancer Awareness Week: A National Initiative for Obstetrics and Gynaecology Residents. AB - OBJECTIVE: The Royal College of Physicians and Surgeons of Canada requires that residents demonstrate competence in health advocacy (HA). We sought to develop and implement a national educational module for obstetrics and gynaecology residents to address the role of HA. This pilot program was centred on cervical cancer prevention, which lends itself to applying the principles of advocacy. METHODS: An educational module was developed and disseminated to all obstetrics and gynaecology residency programs in Canada. The module describes options for HA involving cervical dysplasia screening, such as an outreach clinic or a forum for public/student education, which were to be implemented during Cervical Cancer Awareness Week. The measures of success were the number of programs implementing the curriculum, number of residents who participated, diversity of projects implemented, individuals (patients or learners) reached by the program, and the overall experience of the trainees. RESULTS: Three programs implemented the curriculum in 2011, one in 2012, and seven in 2013. After three years, the module has involved seven of 16 medical schools, over 100 residents, and thousands of women either directly or indirectly. Additionally, attributes of HA experienced by the residents were identified: teamwork, leadership, increased systems knowledge, increased social capital within the community, creativity, innovation, and adaptability. CONCLUSION: We have demonstrated that an educational module can be implemented nationally, helping our residents fulfill their HA requirements. Other specialties could use this module in building HA into their own programs. PMID- 26366823 TI - A Focus on Maternal Health Before Assisted Reproduction: Results From a Pilot Survey of Canadian IVF Medical Directors. AB - OBJECTIVE: To describe current physician practice patterns in Canada with regard to performing in vitro fertilization in high-risk patients. METHODS: All medical directors of IVF clinics registered with the Canadian Fertility and Andrology Society (n=35) were invited to participate in an online survey between January and May 2014. We carried out descriptive analyses of participants' responses regarding implementation of local restrictive policies for access to IVF. Whether practice patterns differed in hospital versus community-based clinics was assessed using chi-square testing with significance set at alpha<0.05. RESULTS: The response rate was 77.1%. More than one half of clinics (55.6%) were university-affiliated, and 29.6% were hospital-based. The majority of respondents (70.4%) used an upper age limit for permitting IVF (median 50 years, IQR 44 to 50), mostly because of lower pregnancy and live birth rates. Approximately one half of respondents limited treatment according to BMI (median upper permitted BMI 38 kg/m2, IQR 35 to 40 kg/m2) to minimize complications during pregnancy. Most respondents (77.8%) believed that routine pre-IVF medical assessment would be useful in their daily practice. There was a non-significant trend towards more restrictive policies in hospital-based clinics compared with community-based clinics. CONCLUSION: Our findings confirm that Canadian reproductive medicine physicians are taking maternal health factors into consideration when assessing patients' suitability for IVF. Nevertheless, there is between-clinic variability in the parameters used to assess eligibility for treatment. In light of the changing maternal demographic, more research is needed on assisted reproductive technology and perinatal outcomes in women who are at risk for pregnancy complications. PMID- 26366822 TI - Critical Appraisal Skills Among Canadian Obstetrics and Gynaecology Residents: How Do They Fare? AB - OBJECTIVES: Evidence-based medicine has become the standard of care in clinical practice. In this study, our objectives were to (1) determine the type of epidemiology and/or biostatistical training being given in Canadian obstetrics and gynaecology post-graduate programs, (2) determine obstetrics and gynaecology residents' level of confidence with critical appraisal, and (3) assess knowledge of fundamental biostatistical and epidemiological principles among Canadian obstetrics and gynaecology trainees. METHODS: During a national standardized in training examination, all Canadian obstetrics and gynaecology residents were invited to complete an anonymous cross-sectional survey to determine their levels of confidence with critical appraisal. Fifteen critical appraisal questions were integrated into the standardized examination to assess critical appraisal skills objectively. Primary outcomes were the residents' level of confidence interpreting biostatistical results and applying research findings to clinical practice, their desire for more biostatistics/epidemiological training in residency, and their performance on knowledge questions. RESULTS: A total of 301 of 355 residents completed the survey (response rate=84.8%). Most (76.7%) had little/no confidence interpreting research statistics. Confidence was significantly higher in those with increased seniority (OR=1.93), in those who had taken a previous epidemiology/statistics course (OR=2.65), and in those who had prior publications (OR=1.82). Many (68%) had little/no confidence applying research findings to clinical practice. Confidence increased significantly with increasing training year (P<0.001) and with formal epidemiology training during residency (OR=2.01). The mean score of the 355 residents on the knowledge assessment questions was 69.8%. Increasing seniority was associated with improved overall test performance (P=0.02). Poorer performance topics included analytical study method (9.9%), study design (36.9%), and sample size (42.0%). Most (84.4%) wanted more epidemiology teaching. CONCLUSION: Canadian obstetrics and gynaecology residents may have the biostatistical and epidemiological knowledge to interpret results published in the literature, but lack confidence applying these skills in clinical settings. Most residents want additional training in these areas, and residency programs should include training in formal curriculums to improve their confidence and prepare them for a lifelong practice of evidence based medicine. PMID- 26366824 TI - Prenatal Diagnosis Procedures and Techniques to Obtain a Diagnostic Fetal Specimen or Tissue: Maternal and Fetal Risks and Benefits. AB - OBJECTIVE: To provide maternity care providers and their patients with current evidence-based guidelines for maternal risk/benefit counselling for a prenatally identified at-risk pregnancy that requires ultrasound-guided prenatal diagnostic procedures and/or techniques for a genetic diagnosis and for subsequent pregnancy management decisions on questions such as level of obstetrical care provider, antenatal surveillance, location of care and delivery, and continuation or termination of pregnancy. This guideline is limited to maternal risk/benefit counselling and pregnancy management decisions for women who require, or are considering, an invasive ultrasound-guided procedure or technique for prenatal diagnosis. PATIENT POPULATION: Pregnant women identified as having an increased risk of a fetal genetic abnormality secondary to the process of established prenatal screening protocols (maternal serum+/-imaging, high-risk cell-free DNA results, abnormal diagnostic fetal imaging, or a positive family history of an inherited condition). These women may require or request counselling about pregnancy risks and benefits of an invasive ultrasound-guided procedure to determine the etiology, diagnosis, and/or pathology for the possible fetal anomaly or anomalies. EVIDENCE: Published literature was retrieved through searches of Medline, PubMed, and the Cochrane Library in and prior to June 2014 using an appropriate controlled vocabulary (prenatal diagnosis, amniocentesis, chorionic villi sampling, cordocentesis) and key words (prenatal screening, prenatal genetic counselling, post-procedural pregnancy loss rate). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies written in English and published from January 1985 to June 2014. Searches were updated on a regular basis and incorporated in the guideline to June 2014. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical speciality societies. VALUES: The quality of evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table 1). Health benefits, side effects, and risks: Patient informed consent, knowledge translation, genetic prenatal risk assessment, anxiety relief, anxiety creation, advocacy, understanding or limitation for fetal testing, pregnancy management choice, pregnancy complication or loss, timely and improved care for birth of a neonate with recognized morbidity. Recommendations 1. The health care provider should counsel the at-risk pregnant woman on the different levels of genetic fetal testing in order for her to have a clear understanding and expectation of the level of testing and type of results that are offered. (III-B) 2. As part of the informed consent process, the health care provider should review with the at risk pregnant woman the risks and benefits of in utero genetic diagnostic techniques associated with fetal genetic testing options. (III-A) 3. During risk/benefit counselling, the health care provider should advise that the best estimate of the pregnancy loss rate related to: a.amniocentesis is 0.5% to 1.0% (range 0.17 to 1.53%) (I) b.chorionic villus sampling is 0.5% to 1.0% (I) and c.cordocentesis or percutaneous umbilical blood sampling is 1.3% for fetuses with no anomalies and 1.3% to 25% for fetuses with single or multiple anomalies or intrauterine growth restriction. (II-2A). PMID- 26366825 TI - Complete mitochondrial genome of Schlegel's Japanese gecko Gekko japonicus (Squamata: Gekkonidae). AB - We have determined the complete mitochondrial genome of Gekko japonicus, whose status as an endemic or invasive species is currently under debate in Korea. The total genome size is 16 544 bp and consists of 13 protein-coding genes, 2 rRNA (12S and 16S RNA) genes, 22 tRNAs and 2 non-coding regions. The A + T content of the genome is 55.8% (A, 31.2%; C, 29.4%; T, 24.6%; G, 14.9%). Phylogenetic analysis shows that G. japonicus has a close phylogenetic relationship with both G. swinhonis and G. chinensis. Our result will facilitate further genetic studies of this species to ascertain its species status. PMID- 26366826 TI - Lupus anticoagulant: a multicenter study for a standardized and harmonized reporting. AB - Laboratory assessment of Lupus anticoagulant (LAC) is very challenging because of inter and intralaboratory variability, which makes it difficult to standardize and harmonize results expression. Five hospital laboratories in North-eastern Italy shared their efforts and their experience in a cross-laboratory study, conducting the diagnostic process as homogeneously as possible and providing a better interpretation for LAC positivity. Hundred normal samples from healthy subjects (20 from each center) were processed to confirm negative upper limits and calculate positivity cutoffs of LAC integrated assays, that is dilute Russell's viper venom time (dRVVT) and silica clotting time (SCT). Moreover, 311 samples previously diagnosed by the laboratories as positive for LAC were analyzed to characterize different positivity levels for each assay. As far as the analysis of healthy subjects is concerned, negative upper limits are set at 1.17 and 1.19 for dRVVT and SCT screen ratio, respectively. Positivity cutoffs are set at 1.20 for dRVVT and 1.23 for SCT, expressed as Test Ratio calculated on screen and confirm integrated tests. Positive results for each integrated assay are subsequently divided into three subgroups: weak, moderate and strong; the results obtained are presented as a score proposal that can provide LAC interpretation. The combined use of both dRVVT and SCT assays and the definition of different positivity levels may lead to clearer, more objective LAC reporting. An interpretative table for LAC-proposed score provides LAC-positive results and it is now adopted by all centers involved in the study. PMID- 26366827 TI - Low platelet activity predicts 30 days mortality in patients undergoing heart surgery. AB - Despite advanced techniques and improved clinical outcomes, patient survival following coronary artery bypass grafting (CABG) is still a major concern. Therefore, predicting future CABG mortality represents an unmet medical need and should be carefully explored. The objective of this study is to assess whether pre-CABG platelet activity corresponds with 30 days mortality post-CABG. Retrospective analyses of platelet biomarkers and death at 30 days in 478 heart surgery patients withdrawn from aspirin or/and clopidogrel. Platelet activity was assessed prior to CABG for aspirin (ASPI-test) with arachidonic acid and clopidogrel (ADP-test) utilizing Multiplate impedance aggregometer. Most patients (n = 198) underwent conventional CABG, off-pump (n = 162), minimally invasive (n = 30), artificial valve implantation (n = 48) or valves in combination with CABG (n = 40). There were 22 deaths at 30 days, including 10 in-hospital fatalities. With the cut-off value set below 407 area under curve (AUC) for the ASPI-test, the 30-day mortality was 5.90% for the lower cohort and 2.66% for patients with significantly higher platelet reactivity (P = 0.038). For the ADP-test with a cut off at 400AUC, the 30-day mortality was 9.68% for the lower cohort and 3.66% for patients with higher platelet reactivity, representing a borderline significant difference (P = 0.046). Aside from the platelet indices, patients who received red blood cell (RBC) concentrate had a highly significant (P < 0.0001) risk of death at 30 days. Both aspirin and clopidogrel tests were useful in predicting 30 days mortality following heart surgery, suggesting the danger of diminished platelet activity prior to CABG in such high-risk patients. These preliminary evidence supports early discontinuation of antiplatelet therapy for elective CABG and requires adequately powered randomized trials to test the hypothesis and potentially improve survival. PMID- 26366828 TI - The expression of ADAMTS13 in human microvascular endothelial cells. AB - ADAMTS13, as a specific von Willebrand factor (VWF)-cleaving protease, prevents microvascular thrombosis of VWF/platelet thrombi. It has been reported that human vascular endothelial cells could also synthesize and secrete ADAMTS13, and these reports were focused in human umbilical vascular endothelial cells. Considering the particularity of its huge quantity and structure of human microvascular endothelial cells (HMECs) in the body, whether ADAMTS13 is expressed in HMECs also needs to be confirmed. To investigate whether ADAMTS13 is expressed in HMECs. Real-time PCR (RT-PCR) amplification detected ADAMTS13 mRNA in HMEC-1 cell line. The expression and distribution of ADAMTS13 protein and VWF were detected by fluorescence immunoassay and western blot. We observed the expression and distribution of ADAMTS13 in HMECs. We confirmed the expression of ADAMTS13 mRNA in HMEC-1, and found that there were some partly common distributions of ADAMTS13 protein and VWF. This study provides the evidence that HMECs also express ADAMTS13. HMECs might also be a primary source for human plasma ADAMTS13. The overlap region for the distribution of ADAMTS13 and VWF suggests that ADAMTS13 might have a potential regulation role for VWF inside cells. PMID- 26366829 TI - Clinical characteristics of pulmonary embolism with concomitant pneumonia. AB - Although pneumonia is associated with an increased risk of venous thromboembolism, patients with pulmonary embolism and concomitant pneumonia are uncommon. The aim of the present study was to investigate the clinical features of pulmonary embolism with coexisting pneumonia. We retrospectively compared clinical, radiologic and laboratory parameters between patients with pulmonary embolism and concomitant pneumonia (pneumonia group) and those with unprovoked pulmonary embolism (unprovoked group), and then between the pneumonia group and those with pulmonary infarction (infarction group). Of 794 patients with pulmonary embolism, 36 (5%) had coexisting pneumonia and six (1%) had no provoking factor other than pneumonia. Stroke was significantly more common in the pneumonia group, than either the unprovoked group or the infarction group. In the pneumonia group, fever was significantly more common and serum C-reactive protein levels were significantly higher. By contrast, central pulmonary embolism and right ventricular dilation on computed tomography were significantly less frequent in the pneumonia group. In addition, an adverse outcome due to pulmonary embolism was less common in the pneumonia group than in either of the other two groups. The coexistence of pulmonary embolism and pneumonia is rarely encountered in clinical practice, especially without the presence of other factors that could provoke venous thromboembolism and is commonly associated with stroke. It is characterized by lower incidences of central pulmonary embolism and right ventricular dilation and by a lower rate of adverse outcomes due to pulmonary embolism itself. PMID- 26366830 TI - The incidence of venous thromboembolism following total knee arthroplasty: a prospective study by using computed tomographic pulmonary angiography in combination with bilateral lower limb venography. AB - Venous thromboembolism (VTE), presenting as deep vein thrombosis (DVT) and pulmonary embolism, is one of the major complications following total knee arthroplasty (TKA). We conducted this prospective observational study to identify the prevalence of VTE among patients undergoing TKA by using computed tomographic pulmonary angiography in combination with bilateral lower limb venography. We enrolled consecutive patients admitted to our institution for primary unilateral TKA from September 2013 to July 2014. All participants underwent a standard surgical procedure of TKA. Computed tomographic pulmonary angiography and bilateral lower limb venography were performed within a week after the operation. We compared age, sex, BMI, comorbidities, data of laboratory tests, operation time and thromboprophylaxis between VTE group and non-VTE group to identify the risk factors. A total of 109 patients were enrolled in this study. The incidence of symptomatic DVT, asymptomatic DVT, symptomatic pulmonary embolism and asymptomatic pulmonary embolism following TKA was 4.6, 18.3, 1.8 and 1.8%, respectively. Elevated level of D-dimer was significantly associated with postoperative VTE. The incidence of VTE following TKA was high despite thromboprophylaxis, and asymptomatic DVTs accounted for a large proportion of thrombotic events. PMID- 26366831 TI - Acenocoumarol vs. low-dose dabigatran in real-world patients discharged after ischemic stroke. AB - The aim of this study was to compare the efficacy of dabigatran 110 mg twice daily and acenocoumarol in patients with atrial fibrillation discharged after ischemic stroke. We prospectively studied 436 consecutive patients who were discharged after acute ischemic stroke (39.2% males, age 78.6 +/- 6.7 years). Approximately 1 year after discharge, the functional status was assessed with the modified Rankin scale (mRS). Adverse outcome was defined as mRS between 2 and 6. The occurrence of ischemic stroke, myocardial infarction (MI) and death during the 1-year follow-up was also recorded. At discharge, 142 patients had atrial fibrillation. Acenocoumarol and dabigatran 110 mg twice daily were prescribed to 52.1 and 6.3% of these patients, respectively. At 1 year after discharge, there was a trend for patients treated with acenocoumarol to have lower mRS than patients prescribed dabigatran (2.3 +/- 2.4 and 4.1 +/- 2.2, respectively; P = 0.060). Adverse outcome rates and the incidence of stroke during follow-up did not differ between the two groups. The incidence of MI was almost three times higher in patients prescribed dabigatran than in those prescribed acenocoumarol, but this difference did not reach significance (11.1 and 4.0%, respectively; P = 0.254). The incidence of cardiovascular death was also almost three times higher in the former, but again this difference was not significant (33.3 and 12.2%, respectively; P = 0.237). In real-world patients with acute ischemic stroke, dabigatran 110 mg twice daily is as effective as acenocoumarol in preventing stroke but appears to be associated with worse long-term functional outcome and higher incidence of MI. PMID- 26366832 TI - Amiodarone-Induced Life-Threatening Refractory Hypotension. AB - BACKGROUND: Amiodarone is frequently used in emergency departments for treatment of arrhythmias. Incidence of several amiodarone-related adverse events is unknown. The literature is sparse for potentially life-threatening adverse effects of amiodarone. CASE REPORT: We present a case of a male patient who presented with chest discomfort and rapid atrial fibrillation. He was known to have paroxysmal atrial fibrillation, which did not respond to initial beta blocker treatment. The second-line drug amiodarone was given to the patient for rate control. He developed severe hypotension related to amiodarone and required inotropic support along with rapid-sequence intubation. CONCLUSIONS: Intravenous amiodarone can cause severe and refractory hypotension. PMID- 26366833 TI - Evolution of blood-brain barrier damage associated with changes in brain metabolites following acute ischemia. AB - Stroke is a serious medical condition that requires emergency care. In the case of ischemic stroke, ischemia may lead to damage to the blood-brain barrier (BBB); the damage in turn may exacerbate the condition. Therefore, noninvasive detection of BBB damage represents a challenge for experimental and clinical researchers. In this study, we assessed the onset of BBB disruption by means of T1-weighted images with administration of the contrast enhancement agent gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) and related BBB breakdown to brain metabolite changes in proton magnetic resonance spectrum (H-MRS) in the infarcted site following middle cerebral artery occlusion (MCAO) in rats. It was shown that MCAO for 30 min and 1.5 h caused no Gd-DTPA signal change in the T1-weighted images, whereas MCAO for 1 h significantly altered some of H-MRS brain metabolites, suggesting that brain metabolite changes occurred earlier than BBB damage after ischemic stroke. MCAO for 2 h caused BBB breakdown, which was related to changes in the levels of some brain metabolites detected by H-MRS. Between the second and the third hour after MCAO, brain metabolite changes continued as the result of BBB breakdown and the concurrent overperfusion to the infarcted site, which may ameliorate the metabolite changes, thus compensating for the functional failures of the brain after stroke. PMID- 26366834 TI - The cross-talk of LDL-cholesterol with cell motility: insights from the Niemann Pick Type C1 mutation and altered integrin trafficking. AB - Cholesterol is considered indispensible for the recruitment and functioning of integrins in focal adhesions for cell migration. However, the physiological cholesterol pools that control integrin trafficking and focal adhesion assembly remain unclear. Using Niemann Pick Type C1 (NPC) mutant cells, which accumulate Low Density lipoprotein (LDL)-derived cholesterol in late endosomes (LE), several recent studies indicate that LDL-cholesterol has multiple roles in regulating focal adhesion dynamics. Firstly, targeting of endocytosed LDL-cholesterol from LE to focal adhesions controls their formation at the leading edge of migrating cells. Other newly emerging literature suggests that this may be coupled to vesicular transport of integrins, Src kinase and metalloproteases from the LE compartment to focal adhesions. Secondly, our recent work identified LDL cholesterol as a key factor that determines the distribution and ability of several Soluble NSF Attachment Protein (SNAP) Receptor (SNARE) proteins, key players in vesicle transport, to control integrin trafficking to the cell surface and extracellular matrix (ECM) secretion. Collectively, dietary, genetic and pathological changes in cholesterol metabolism may link with efficiency and speed of integrin and ECM cell surface delivery in metastatic cancer cells. This commentary will summarize how direct and indirect pathways enable LDL-cholesterol to modulate cell motility. PMID- 26366835 TI - Ability of Antibiotic-Resistant Nonvaccine-Type Pneumococcal Clones to Cause Otitis Media in an Infant Mouse Model of Pneumococcal-Influenza Virus Coinfection. AB - The introduction of the 7-valent pneumococcal conjugate vaccine in Portugal resulted in reduced carriage in children by vaccine-type strains and an increased carriage of three major antibiotic-resistant clones, ST2191, ST276, and ST63 expressing capsules 6A, 19A, and 15A, respectively. Pneumococcal otitis media (OM), a frequent infection among preschool age children, is often associated with viral coinfection. To evaluate the ability of these three antibiotic-resistant clones to cause disease, we used an infant mouse model of influenza virus pneumococcal coinfection. The 6A and 19A clonal types induced OM, while 15A induced pneumococcal pneumonia and bloodstream infection, suggesting potential for invasive disease. PMID- 26366836 TI - Efficacy and Safety of Mechanical Thrombectomy in Treating Acute Ischemic Stroke: A Meta Analysis. AB - OBJECTIVES: Mechanical thrombectomy (MT) is a promising treatment for acute ischemic stroke (AIS). But the results of completed trials were contradictory. Hence, we performed a meta-analysis to evaluate the efficacy and safety of MT in treating AIS. METHODS: Literatures were searched in the databases including Pubmed, Cochrane Library, Web of Science and Ovid-SP. The bias and quality of publications with randomized controlled trials (RCTs) were assessed with the Cochrane collaboration's tool for assessing risk of bias. RESULTS: Totally 16 publications matched the inclusion criteria, including seven independent RCTs and 2043 AIS patients. The results showed that the recanalization rate and the modified Rankin score of 0-2 at 90 days after treatment were better in MT combining standard care group, but the mortality had no significant difference, even the incidence of intracerebral hemorrhage during follow-up period was worse, as compared with standard care group. CONCLUSION: MT combining standard care would be an effective and promising treatment for AIS patients according to the present study. PMID- 26366838 TI - Is obesity an advantage in patients with colorectal cancer? AB - Obesity/higher BMI appears to be important determinants in the development of colon cancer as well as in predicting outcomes in the adjuvant setting in these patients. These associations seem to be stronger for men and tend to be 'J shaped', with worse outcomes in both lower and upper BMI categories than in the middle categories. How this factors in the metastatic setting is less clear. A recent pooled analysis of patients with metastatic colorectal cancer receiving bevacizumab in the first-line setting observed that patients with the lowest BMI had the lowest median overall survival. An incremental BMI increase of 5 kg/m(2) led to actually a decrease in the risk of death (hazard ratio, 0.911 [95% CI, 0.879-0.944]). The observed association does not necessarily mean that obesity is an advantage for patients with metastatic colorectal cancer. More likely, it is conceivable that, in patients with metastatic colorectal cancer with a lower BMI, the effects of cancer-related cachexia may be more deleterious than the potential adverse events related to a higher BMI. In patients already diagnosed with metastatic disease, studying how body weight affects tumor biology and treatment related decisions are important considerations. PMID- 26366837 TI - Expression of ER stress markers (GRP78/BiP and PERK) in adenoid cystic carcinoma. AB - CONCLUSION: A high GRP78/BiP expression was proved to be a significant marker for predicting poor outcome after surgery. GRP78/BiP may be a promising molecular target for treatment of ACC. BACKGROUND: The glucose-regulated protein GRP78/BiP plays a crucial role in the endoplasmic reticulum (ER) stress. The level of GRP78 is highly elevated in various human cancers, but the clinicopathological significance of GRP78/BiP remains controversial in patients with adenoid cystic carcinoma (ACC). METHODS: A total of 26 ACC patients were analyzed, and tumor specimens were stained by immunohistochemistry for GRP78/BiP, PERK, Ki-67, and microvessel density (MVD) determined by CD34. RESULTS: GRP78/BiP and PERK were highly expressed in 58% (15/26) and 35% (9/26), respectively. The high expression of GRP78/BiP was significantly associated with PERK, cell proliferation and angiogenesis. PMID- 26366842 TI - Perception of Discomfort Caused by a Unilateral Hearing Loss in People Suffering from a Total Bilateral Vestibular Loss. AB - The quality of life of patients suffering from a bilateral vestibular loss is severely altered. Patients mainly complain of oscillopsia, imbalance, and spatial disorientation. Up to now, there is no efficient treatment. Some teams around the world are working on the development of a vestibular implant for the restoration of the vestibular function based on the concept similar to that of a cochlear implant, stimulating the neural vestibular pathways through electrical pulses. There are different potential stimulation sites of the vestibular system, all raising the major concern about a potential hearing loss in the implanted ear. As this implant does not exist yet, patients cannot be informed of the risk of hearing loss due to the surgical intervention versus the benefits brought by the vestibular prosthesis. In order to better inform future vestibular implant candidates, we need to evaluate the handicap of patients with an actual unilateral hearing loss, and to compare it to the way that patients suffering from a bilateral vestibular loss perceive a potential unilateral hearing loss. For this, we used the HHIA questionnaire (Hearing Handicap Inventory for Adults) on 3 groups of participants, i.e. patients with a unilateral hearing loss, patients suffering from a bilateral vestibular loss but having normal hearing, and healthy subjects. The scores reported by patients with a unilateral hearing loss were much lower than those of the other 2 groups, indicating that people whose hearing is normal overstate the disability related to a unilateral hearing loss. Patients to whom a vestibular implant is proposed in order to correct their balance disorders may use this information to decide whether or not to choose an operation. PMID- 26366840 TI - Phytoaccumulation of Heavy Metals in Natural Vegetation at the Municipal Wastewater Site in Abbottabad, Pakistan. AB - Heavy metal accumulation in crops and soils from wastewater irrigation poses a significant threat to the human health. A study was carried out to investigate the removal potential of heavy metals (HM) by native plant species, namely Cannabis sativa L., Chenopodium album L., Datura stramonium L., Sonchus asper L., Amaranthus viridus L., Oenothera rosea (LHer), Xanthium stramonium L., Polygonum macalosa L., Nasturtium officinale L. and Conyza canadensis L. growing at the municipal wastewater site in Abbottabad city, Pakistan. The HM concentrations varied among plants depending on the species. Metal concentrations across species varied in the order iron (Fe) > zinc (Zn) > chromium (Cr) > nickel (Ni) > cadmium (Cd). Majority of the species accumulated more HM in roots than shoots. Among species, the concentrations (both in roots and shoots) were in the order C. sativa > C. album > X. stramonium > C. canadensis > A. viridus > N. officinale > P. macalosa > D. stramonium > S. asper > O. rosea. No species was identified as a hyperaccumulator. All species exhibited a translocation factor (TF) less than 1. Species like C. sativa, C. album and X. stramonium gave higher (> 1) biological concentration factor (BCF) and biological accumulation coefficient (BAC) especially for Fe, Cr and Cd than other species. Higher accumulation of heavy metals in these plant species signifies the general application of these species for phytostabilization and phytoextraction of HM from polluted soils. PMID- 26366843 TI - Imaging in Inflammatory Bowel Diseases - Magnetic Resonance Imaging. AB - Diagnostic imaging techniques play an important role in the diagnosis and management of patients with inflammatory bowel diseases (IBDs). The approach should be guided by considerations of diagnostic accuracy, concerns about patient exposure to ionizing radiation, local expertise and tolerance of the endoscopic and/or imaging technique. In regard to the clinical diagnostic value (sensitivity, specificity and accuracy), no significant differences exist between CT and MRI for the evaluation of the extent of inflammation, stricturing, penetrating disease or extraluminal complications such as abscesses. Due to the absence of radiation exposure, MRI of the intestine is recommended as the first line imaging modality in patients with suspected or established IBD. The focus of this review is the latest developments in MRI techniques to detect IBDs. Specifically, the use of new indices for the grading of inflammation or assessing bowel damage as well as innovative experimental approaches such as diffusion weighted imaging or magnetization-transfer MRI to evaluate and quantify the degree of intestinal inflammation and fibrosis in stricturing Crohn's disease are discussed. PMID- 26366845 TI - Reflexions on some aspects of the interactions among ROS, RNS, and Ca(2+) in response to a mycorrhizal or a pathogenic fungus. AB - In vivo redox activities in the apoplast of axenically cultured intact seedling roots (superoxide anion generation, and superoxide dismutase and peroxidase activities) in contact with the compatible arbuscular mycorrhizal fungus (AMF) were clearly attenuated in comparison with those in contact with the pathogenic fungus (PF) or treated with MeJA, even at the early stages of treatment. Contact of roots with the AMF did not enhance the biosynthesis of phenolic compounds (total phenolics, flavonoids, and phenylpropanoid glycosides), while contact with the PF significantly enhanced the biosynthesis of all phenolic fractions. Reactive oxygen and nitrogen species both seemed to be involved in these responses from the first moments of contact, but the fluorescence imaging of roots showed that ROS were mainly accumulated in the apoplast while NO was mainly stored in the cytosol. In conclusion, intact olive seedling roots clearly differentiated between AMF and PF. PMID- 26366844 TI - Immunization of pregnant women: Future of early infant protection. AB - Children in early infancy do not mount effective antibody responses to many vaccines against commons infectious pathogens, which results in a window of increased susceptibility or severity infections. In addition, vaccine-preventable infections are among the leading causes of morbidity in pregnant women. Immunization during pregnancy can generate maternal immune protection as well as elicit the production and transfer of antibodies cross the placenta and via breastfeeding to provide early infant protection. Several successful vaccines are now recommended to all pregnant women worldwide. However, significant gaps exist in our understanding of the efficacy and safety of other vaccines and in women with conditions associated with increased susceptible to high-risk pregnancies. Public acceptance of maternal immunization remained to be improved. Broader success of maternal immunization will rely on the integration of advances in basic science in vaccine design and evaluation and carefully planned clinical trials that are inclusive to pregnant women. PMID- 26366846 TI - Organic electronics: Something out of nothing. PMID- 26366847 TI - An electrodeposited inhomogeneous metal-insulator-semiconductor junction for efficient photoelectrochemical water oxidation. AB - The photoelectrochemical splitting of water into hydrogen and oxygen requires a semiconductor to absorb light and generate electron-hole pairs, and a catalyst to enhance the kinetics of electron transfer between the semiconductor and solution. A crucial question is how this catalyst affects the band bending in the semiconductor, and, therefore, the photovoltage of the cell. We introduce a simple and inexpensive electrodeposition method to produce an efficient n Si/SiOx/Co/CoOOH photoanode for the photoelectrochemical oxidation of water to oxygen. The photoanode functions as a solid-state, metal-insulator-semiconductor photovoltaic cell with spatially non-uniform barrier heights in series with a low overpotential water-splitting electrochemical cell. The barrier height is a function of the Co coverage; it increases from 0.74 eV for a thick, continuous film to 0.91 eV for a thin, inhomogeneous film that has not reached coalescence. The larger barrier height leads to a 360 mV photovoltage enhancement relative to a solid-state Schottky barrier. PMID- 26366848 TI - Matrix elasticity of void-forming hydrogels controls transplanted-stem-cell mediated bone formation. AB - The effectiveness of stem cell therapies has been hampered by cell death and limited control over fate. These problems can be partially circumvented by using macroporous biomaterials that improve the survival of transplanted stem cells and provide molecular cues to direct cell phenotype. Stem cell behaviour can also be controlled in vitro by manipulating the elasticity of both porous and non-porous materials, yet translation to therapeutic processes in vivo remains elusive. Here, by developing injectable, void-forming hydrogels that decouple pore formation from elasticity, we show that mesenchymal stem cell (MSC) osteogenesis in vitro, and cell deployment in vitro and in vivo, can be controlled by modifying, respectively, the hydrogel's elastic modulus or its chemistry. When the hydrogels were used to transplant MSCs, the hydrogel's elasticity regulated bone regeneration, with optimal bone formation at 60 kPa. Our findings show that biophysical cues can be harnessed to direct therapeutic stem cell behaviours in situ. PMID- 26366849 TI - Efficient hydrogen evolution catalysis using ternary pyrite-type cobalt phosphosulphide. AB - The scalable and sustainable production of hydrogen fuel through water splitting demands efficient and robust Earth-abundant catalysts for the hydrogen evolution reaction (HER). Building on promising metal compounds with high HER catalytic activity, such as pyrite structure cobalt disulphide (CoS2), and substituting non metal elements to tune the hydrogen adsorption free energy could lead to further improvements in catalytic activity. Here we present a combined theoretical and experimental study to establish ternary pyrite-type cobalt phosphosulphide (CoPS) as a high-performance Earth-abundant catalyst for electrochemical and photoelectrochemical hydrogen production. Nanostructured CoPS electrodes achieved a geometrical catalytic current density of 10 mA cm(-2) at overpotentials as low as 48 mV, with outstanding long-term operational stability. Integrated photocathodes of CoPS on n(+)-p-p(+) silicon micropyramids achieved photocurrents up to 35 mA cm(-2) at 0 V versus the reversible hydrogen electrode (RHE), onset photovoltages as high as 450 mV versus RHE, and the most efficient solar-driven hydrogen generation from Earth-abundant systems. PMID- 26366850 TI - Conductivity in organic semiconductors hybridized with the vacuum field. AB - Much effort over the past decades has been focused on improving carrier mobility in organic thin-film transistors by optimizing the organization of the material or the device architecture. Here we take a different path to solving this problem, by injecting carriers into states that are hybridized to the vacuum electromagnetic field. To test this idea, organic semiconductors were strongly coupled to plasmonic modes to form coherent states that can extend over as many as 10(5) molecules and should thereby favour conductivity. Experiments show that indeed the current does increase by an order of magnitude at resonance in the coupled state, reflecting mostly a change in field-effect mobility. A theoretical quantum model confirms the delocalization of the wavefunctions of the hybridized states and its effect on the conductivity. Our findings illustrate the potential of engineering the vacuum electromagnetic environment to modify and to improve properties of materials. PMID- 26366851 TI - Pain and Prejudice. PMID- 26366852 TI - Wetting transition of the caterpillar-like superhydrophobic Cu/Ni-Co hierarchical structure by heat treatment. AB - Caterpillar-like hierarchical structured Cu/Ni-Co coatings were fabricated by a simple two-step method of combined electroless and electrodeposition. Both contact angles and sliding angles were measured to investigate the hydrophobicity after stearic acid modification. The results revealed the contact angle was as high as 165.5 degrees (superhydrophobic), while the sliding angle was only 3.5 degrees , which makes it very promising as self-cleaning material. Wetting transition from slippery hydrophobicity to sticky hydrophobicity happened upon heat treatment. The scanning electron microscopy (SEM) analysis disclosed the morphology change of the hierarchical structure during the heat treatment leading to the wetting state transition. Different models of wetting states were raised and calculated to provide further confirmation of the transition. The contact angle remained larger than 156 degrees when the pH value ranged from 1 to 14 and the heat-treatment temperature was from 100 to 250 degrees C. Such hierarchical micronanostructure and its special hydrophobicity are expected to have practical application in industry. PMID- 26366853 TI - B(OCH2CF3)3-mediated direct amidation of pharmaceutically relevant building blocks in cyclopentyl methyl ether. AB - The use of B(OCH2CF3)3 for mediating direct amidation reactions of a wide range of pharmaceutically relevant carboxylic acids and amines is described, including numerous heterocycle-containing examples. An initial screen of solvents for the direct amidation reaction suggested that cyclopentyl methyl ether, a solvent with a very good safety profile suitable for use over a wide temperature range, was an excellent replacement for the previously used solvent acetonitrile. Under these conditions amides could be prepared from 18 of the 21 carboxylic acids and 18 of the 21 amines examined. Further optimisation of one of the low yielding amidation reactions (36% yield) via a design of experiments approach enabled an 84% yield of the amide to be obtained. PMID- 26366854 TI - Mechanistic insights into nitrogen fixation by nitrogenase enzymes. AB - Biological nitrogen fixation by nitrogenase enzymes is a process that activates dinitrogen (N2) one of the most inert molecules in nature, within the confines of a living organism and at ambient conditions. Despite decades of study, there are still no complete explanations as to how this is possible. Here we describe a model of N2 reduction using the Mo-containing nitrogenase (FeMoco) that can explain the reactivity of the active site via a series of electrochemical steps that reversibly unseal a highly reactive Fe edge site. Our model can explain the 8 proton-electron transfers involved in biological ammonia synthesis within the kinetic scheme of Lowe and Thorneley, the obligatory formation of one H2 per N2 reduced, and the behavior of known inhibitors. PMID- 26366855 TI - Improved recombinant Api m 1- and Ves v 5-based IgE testing to dissect bee and yellow jacket allergy and their correlation with the severity of the sting reaction. AB - BACKGROUND: No study has assessed the diagnostic sensitivity of rApi m 1 and rVes v 5 on Immulite testing system. OBJECTIVE: To compare the diagnostic sensitivity of commercially available venom recombinant allergens between the currently available immunoassays [ImmunoCAP (CAP) and Immulite (LITE)] and establish their correlation with the severity of the sting reaction. METHODS: This study evaluated 95 bee venom and 110 yellow jacket venom-allergic subjects. We measured the levels of sIgE to rApi m 1, rVes v 5 (LITE and CAP), rApi m 2 (LITE), rVes v 1 (CAP) and total IgE (CAP). Forty-nine healthy subjects served as controls. RESULTS: The diagnostic sensitivity of rApi m 1 and rVes v 5 was significantly higher with the LITE than with the CAP system (71% vs. 88% and 82% vs. 93%). The specificity of both assays for both allergens was between 94% and 98%. Twenty nine patients that tested negative for rApi m 1 or rVes v 5 with CAP were positive with LITE, but none of the patients that tested negative with LITE were positive with CAP. The positive values of rApi m 1 and rVes v 5 were on average 2.7 and 2.3 times higher, with the LITE than with the CAP system. The combination of rApi m 1 and rApi m 2 (LITE) and the combination of rVes v 5 (LITE) and rVes v 1 (CAP) almost matched the sensitivity of native venoms (95% and 97%, respectively), whereas the diagnostic sensitivity of the combination of rVes v 5 and rVes v 1 (CAP) did not reach the sensitivity of rVes v 5 (LITE) alone (90% vs. 93%). IgE levels to venom recombinants and total IgE did not correlate with the severity of sting reaction. CONCLUSIONS & CLINICAL RELEVANCE: The use of rApi m 1 and rVes v 5 with the LITE system significantly enhanced diagnostic utility of venom recombinants and should improve the dissection of bee and yellow jacket venom allergy. PMID- 26366856 TI - Complete nutrient content of four species of commercially available feeder insects fed enhanced diets during growth. AB - Commercially raised feeder insects used to feed captive insectivores are a good source of many nutrients but are deficient in several key nutrients. Current methods used to supplement insects include dusting and gut-loading. Here, we report on the nutrient composition of four species of commercially raised feeder insects fed a special diet to enhance their nutrient content. Crickets, mealworms, superworms, and waxworms were analyzed for moisture, crude protein, fat, ash, acid detergent fiber, total dietary fiber, minerals, amino acids, fatty acids, vitamins, taurine, carotenoids, inositol, and cholesterol. All four species contained enhanced levels of vitamin E and omega 3 fatty acids when compared to previously published data for these species. Crickets, superworms, and mealworms contained beta-carotene although using standard conversion factors only crickets and superworms would likely contain sufficient vitamin A activity for most species of insectivores. Waxworms did not contain any detectable beta carotene but did contain zeaxanthin which they likely converted from dietary beta carotene. All four species contained significant amounts of both inositol and cholesterol. Like previous reports all insects were a poor source of calcium and only superworms contained vitamin D above the limit of detection. When compared to the nutrient requirements as established by the NRC for growing rats or poultry, these species were good sources of most other nutrients although the high fat and low moisture content of both waxworms and superworms means when corrected for energy density these two species were deficient in more nutrients than crickets or mealworms. These data show the value of modifying the diet of commercially available insects as they are growing to enhance their nutrient content. They also suggest that for most insectivores properly supplemented lower fat insects such as crickets, or smaller mealworms should form the bulk of the diet. PMID- 26366859 TI - Correction: New Operational Matrices for Solving Fractional Differential Equations on the Half-Line. PMID- 26366858 TI - ER Stress Mediates TiAl6V4 Particle-Induced Peri-Implant Osteolysis by Promoting RANKL Expression in Fibroblasts. AB - Wear particle-induced osteolysis is a major cause of aseptic loosening, which is one of the most common reasons for total hip arthroplasty (THA) failure. Previous studies have shown that the synovial fibroblasts present in the periprosthetic membrane are important targets of wear debris during osteolysis. However, the interaction mechanisms between the wear debris and fibroblasts remain largely unknown. In the present study, we investigated the effect of ER (endoplasmic reticulum) stress induced by TiAl6V4 particles (TiPs) in human synovial fibroblasts and calvarial resorption animal models. The expression of ER stress markers, including IRE1-alpha, GRP78/Bip and CHOP, were determined by western blot in fibroblasts that had been treated with TiPs for various times and concentration. To address whether ER stress was involved in the expression of RANKL, the effects of ER stress blockers (including 4-PBA and TUDCA) on the expression of RANKL in TiPs-treated fibroblasts were examined by real-time PCR, western blot and ELISA. Osteoclastogenesis was assessed by tartrate resistant acid phosphatase (TRAP) staining. Our study demonstrated that ER stress markers were markedly upregulated in TiPs-treated fibroblasts. Blocking ER stress significantly reduced the TiPs-induced expression of RANKL both in vitro and in vivo. Moreover, the inhibition of ER stress ameliorated wear particle-induced osteolysis in animal models. Taken together, these results suggested that the expression of RANKL induced by TiPs was mediated by ER stress in fibroblasts. Therefore, down regulating the ER stress of fibroblasts represents a potential therapeutic approach for wear particle-induced periprosthetic osteolysis. PMID- 26366857 TI - Genome-Wide Transcriptome Analysis of Cotton (Gossypium hirsutum L.) Identifies Candidate Gene Signatures in Response to Aflatoxin Producing Fungus Aspergillus flavus. AB - Aflatoxins are toxic and potent carcinogenic metabolites produced from the fungi Aspergillus flavus and A. parasiticus. Aflatoxins can contaminate cottonseed under conducive preharvest and postharvest conditions. United States federal regulations restrict the use of aflatoxin contaminated cottonseed at >20 ppb for animal feed. Several strategies have been proposed for controlling aflatoxin contamination, and much success has been achieved by the application of an atoxigenic strain of A. flavus in cotton, peanut and maize fields. Development of cultivars resistant to aflatoxin through overexpression of resistance associated genes and/or knocking down aflatoxin biosynthesis of A. flavus will be an effective strategy for controlling aflatoxin contamination in cotton. In this study, genome-wide transcriptome profiling was performed to identify differentially expressed genes in response to infection with both toxigenic and atoxigenic strains of A. flavus on cotton (Gossypium hirsutum L.) pericarp and seed. The genes involved in antifungal response, oxidative burst, transcription factors, defense signaling pathways and stress response were highly differentially expressed in pericarp and seed tissues in response to A. flavus infection. The cell-wall modifying genes and genes involved in the production of antimicrobial substances were more active in pericarp as compared to seed. The genes involved in auxin and cytokinin signaling were also induced. Most of the genes involved in defense response in cotton were highly induced in pericarp than in seed. The global gene expression analysis in response to fungal invasion in cotton will serve as a source for identifying biomarkers for breeding, potential candidate genes for transgenic manipulation, and will help in understanding complex plant-fungal interaction for future downstream research. PMID- 26366860 TI - Development of a Three-Dimensional Hand Model Using Three-Dimensional Stereophotogrammetry: Assessment of Image Reproducibility. AB - PURPOSE: Using three-dimensional (3D) stereophotogrammetry precise images and reconstructions of the human body can be produced. Over the last few years, this technique is mainly being developed in the field of maxillofacial reconstructive surgery, creating fusion images with computed tomography (CT) data for precise planning and prediction of treatment outcome. Though, in hand surgery 3D stereophotogrammetry is not yet being used in clinical settings. METHODS: A total of 34 three-dimensional hand photographs were analyzed to investigate the reproducibility. For every individual, 3D photographs were captured at two different time points (baseline T0 and one week later T1). Using two different registration methods, the reproducibility of the methods was analyzed. Furthermore, the differences between 3D photos of men and women were compared in a distance map as a first clinical pilot testing our registration method. RESULTS: The absolute mean registration error for the complete hand was 1.46 mm. This reduced to an error of 0.56 mm isolating the region to the palm of the hand. When comparing hands of both sexes, it was seen that the male hand was larger (broader base and longer fingers) than the female hand. CONCLUSIONS: This study shows that 3D stereophotogrammetry can produce reproducible images of the hand without harmful side effects for the patient, so proving to be a reliable method for soft tissue analysis. Its potential use in everyday practice of hand surgery needs to be further explored. PMID- 26366861 TI - Is the Schwabe Organ a Retained Larval Eye? Anatomical and Behavioural Studies of a Novel Sense Organ in Adult Leptochiton asellus (Mollusca, Polyplacophora) Indicate Links to Larval Photoreceptors. AB - The discovery of a sensory organ, the Schwabe organ, was recently reported as a unifying feature of chitons in the order Lepidopleurida. It is a patch of pigmented tissue located on the roof of the pallial cavity, beneath the velum on either side of the mouth. The epithelium is densely innervated and contains two types of potential sensory cells. As the function of the Schwabe organ remains unknown, we have taken a cross-disciplinary approach, using anatomical, histological and behavioural techniques to understand it. In general, the pigmentation that characterises this sensory structure gradually fades after death; however, one particular concentrated pigment dot persists. This dot is positionally homologous to the larval eye in chiton trochophores, found in the same neuroanatomical location, and furthermore the metamorphic migration of the larval eye is ventral in species known to possess Schwabe organs. Here we report the presence of a discrete subsurface epithelial structure in the region of the Schwabe organ in Leptochiton asellus that histologically resembles the chiton larval eye. Behavioural experiments demonstrate that Leptochiton asellus with intact Schwabe organs actively avoid an upwelling light source, while Leptochiton asellus with surgically ablated Schwabe organs and a control species lacking the organ (members of the other extant order, Chitonida) do not (Kruskal-Wallis, H = 24.82, df = 3, p < 0.0001). We propose that the Schwabe organ represents the adult expression of the chiton larval eye, being retained and elaborated in adult lepidopleurans. PMID- 26366862 TI - An Ancient Divide in a Contiguous Rainforest: Endemic Earthworms in the Australian Wet Tropics. AB - Understanding the factors that shape current species diversity is a fundamental aim of ecology and evolutionary biology. The Australian Wet Tropics (AWT) are a system in which much is known about how the rainforests and the rainforest dependent organisms reacted to late Pleistocene climate changes, but less is known about how events deeper in time shaped speciation and extinction in this highly endemic biota. We estimate the phylogeny of a species-rich endemic genus of earthworms (Terrisswalkerius) from the region. Using DEC and DIVA historical biogeography methods we find a strong signal of vicariance among known biogeographical sub-regions across the whole phylogeny, congruent with the phylogeography of less diverse vertebrate groups. Absolute dating estimates, in conjunction with relative ages of major biogeographic disjunctions across Australia, indicate that diversification in Terrisswalkerius dates back before the mid-Miocene shift towards aridification, into the Paleogene era of isolation of mesothermal Gondwanan Australia. For the Queensland endemic Terrisswalkerius earthworms, the AWT have acted as both a museum of biological diversity and as the setting for continuing geographically structured diversification. These results suggest that past events affecting organismal diversification can be concordant across phylogeographic to phylogenetic levels and emphasize the value of multi-scale analysis, from intra- to interspecies, for understanding the broad scale processes that have shaped geographic diversity. PMID- 26366863 TI - The abcEDCBA-Encoded ABC Transporter and the virB Operon-Encoded Type IV Secretion System of Brucella ovis Are Critical for Intracellular Trafficking and Survival in Ovine Monocyte-Derived Macrophages. AB - Brucella ovis infection is associated with epididymitis, orchitis and infertility in rams. Most of the information available on B. ovis and host cell interaction has been generated using murine macrophages or epithelial cell lines, but the interaction between B. ovis and primary ovine macrophages has not been studied. The aim of this study was to evaluate the role of the B. ovis abcEDCBA-encoded ABC transporter and the virB operon-encoded Type IV Secretion System (T4SS) during intracellular survival of B. ovis in ovine peripheral blood monocyte derived macrophages. DeltaabcBA and DeltavirB2 mutant strains were unable to survive in the intracellular environment when compared to the WT B. ovis at 48 hours post infection (hpi). In addition, these mutant strains cannot exclude the lysosomal marker LAMP1 from its vacuolar membrane, and their vacuoles do not acquire the endoplasmic reticulum marker calreticulin, which takes place in the WT B. ovis containing vacuole. Higher levels of nitric oxide production were observed in macrophages infected with WT B. ovis at 48 hpi when compared to macrophages infected with the DeltaabcBA or DeltavirB2 mutant strains. Conversely, higher levels of reactive oxygen species were detected in macrophages infected with the DeltaabcBA or DeltavirB2 mutant strains at 48 hpi when compared to macrophages infected with the WT strain. Our results demonstrate that B. ovis is able to persist and multiply in ovine macrophages, while DeltaabcBA and DeltavirB2 mutations prevent intracellular multiplication, favor phagolysosome fusion, and impair maturation of the B. ovis vacuole towards an endoplasmic reticulum-derived compartment. PMID- 26366864 TI - Differential Gene Expression across Breed and Sex in Commercial Pigs Administered Fenbendazole and Flunixin Meglumine. AB - Characterizing the variability in transcript levels across breeds and sex in swine for genes that play a role in drug metabolism may shed light on breed and sex differences in drug metabolism. The objective of the study is to determine if there is heterogeneity between swine breeds and sex in transcript levels for genes previously shown to play a role in drug metabolism for animals administered flunixin meglumine or fenbendazole. Crossbred nursery female and castrated male pigs (n = 169) spread across 5 groups were utilized. Sires (n = 15) of the pigs were purebred Duroc, Landrace, Yorkshire or Hampshire boars mated to a common sow population. Animals were randomly placed into the following treatments: no drug (control), flunixin meglumine, or fenbendazole. One hour after the second dosing, animals were sacrificed and liver samples collected. Quantitative Real-Time PCR was used to measure liver gene expression of the following genes: SULT1A1, ABCB1, CYP1A2, CYP2E1, CYP3A22 and CYP3A29. The control animals were used to investigate baseline transcript level differences across breed and sex. Post drug administration transcript differences across breed and sex were investigated by comparing animals administered the drug to the controls. Contrasts to determine fold change were constructed from a model that included fixed and random effects within each drug. Significant (P-value <0.007) basal transcript differences were found across breeds for SULT1A1, CYP3A29 and CYP3A22. Across drugs, significant (P-value <0.0038) transcript differences existed between animals given a drug and controls across breeds and sex for ABCB1, PS and CYP1A2. Significant (P <0.0038) transcript differences across breeds were found for CYP2E1 and SULT1A1 for flunixin meglumine and fenbendazole, respectively. The current analysis found transcript level differences across swine breeds and sex for multiple genes, which provides greater insight into the relationship between flunixin meglumine and fenbendazole and known drug metabolizing genes. PMID- 26366866 TI - Photobleaching and Fluorescence Recovery of RPE Bisretinoids. AB - The autofluorescence of the retina that originates primarily from lipofuscin fluorophores in retinal pigment epithelial cells, is observed to undergo photobleaching during the acquisition of fundus autofluorescence images. Bisretinoid fluorophores isolated from retinal pigment epithelial cells have the spectral characteristics consistent with their being the source of fundus autofluorescence. Clinically relevant experiments were designed to better understand conditions in the micromilieu of bisretinoid fluorophores that can influence fluorescence efficiencies, photobleaching, and subsequent fluorescence recovery of this fluorophore. The consumption of the bisretinoid A2E due to photooxidation-induced degradation was quantified in solvent systems of variable relative permittivity (formerly called dielectric constant), in micelles, and in phospholipid vesicles of varying composition. Reorganization within biphasic systems was also examined. A2E content was measured by high performance liquid chromatography (HPLC) and fluorescence intensity was quantified spectroscopically. As solvent polarity was increased, A2E fluorescent spectra exhibited red-shifted maxima and reduced intensity. A2E was depleted by light irradiation and the loss was more pronounced in less polar solvents, lower concentrations of anionic surfactant, and in gel- versus fluid-ordered phospholipid liposomes. Conditions that permit A2E aggregation promoted photooxidation/photodegradation, while movement of A2E between bisphasic systems was associated with fluorescence recovery after photobleaching. The fluorescence characteristics of A2E are subject to environmental modulation. Photooxidation and photodegradation of bisretinoid can account for fundus autofluorescence photobleaching. Return of fluorescence intensity after photobleaching likely occurs due to redistribution of A2E fractions amongst co-existing heterogeneous microdomains of the lysosomal compartment. PMID- 26366865 TI - Inhaled Carbon Monoxide Protects against the Development of Shock and Mitochondrial Injury following Hemorrhage and Resuscitation. AB - AIMS: Currently, there is no effective resuscitative adjunct to fluid and blood products to limit tissue injury for traumatic hemorrhagic shock. The objective of this study was to investigate the role of inhaled carbon monoxide (CO) to limit inflammation and tissue injury, and specifically mitochondrial damage, in experimental models of hemorrhage and resuscitation. RESULTS: Inhaled CO (250 ppm for 30 minutes) protected against mortality in severe murine hemorrhagic shock and resuscitation (HS/R) (20% vs. 80%; P<0.01). Additionally, CO limited the development of shock as determined by arterial blood pH (7.25+/-0.06 vs. 7.05+/ 0.05; P<0.05), lactate levels (7.2+/-5.1 vs 13.3+/-6.0; P<0.05), and base deficit (13+/-3.0 vs 24+/-3.1; P<0.05). A dose response of CO (25-500 ppm) demonstrated protection against HS/R lung and liver injury as determined by MPO activity and serum ALT, respectively. CO limited HS/R-induced increases in serum tumor necrosis factor-alpha and interleukin-6 levels as determined by ELISA (P<0.05 for doses of 100-500ppm). Furthermore, inhaled CO limited HS/R induced oxidative stress as determined by hepatic oxidized glutathione:reduced glutathione levels and lipid peroxidation. In porcine HS/R, CO did not influence hemodynamics. However, CO limited HS/R-induced skeletal muscle and platelet mitochondrial injury as determined by respiratory control ratio (muscle) and ATP-linked respiration and mitochondrial reserve capacity (platelets). CONCLUSION: These preclinical studies suggest that inhaled CO can be a protective therapy in HS/R; however, further clinical studies are warranted. PMID- 26366867 TI - Lack of ROS1 Gene Rearrangement in Glioblastoma Multiforme. AB - Glioblastoma multiforme (GBM) is the most aggressive type of brain tumor, and the prognosis remains poor. Rearrangement of ROS1 gene, which was shown to have an oncogenic potential, was previously discovered in GBM cell lines. In this pilot study, we aimed to identify the incidence of ROS1 rearrangement in GBM patient tissues to explore novel biomarkers for therapeutic strategy. Formalin-fixed and paraffin-embedded (FFPE) tissue sections from 109 patients with GBM were screened for ROS1 rearrangement by anti-ROS immunohistochemistry (IHC) and ROS1 break apart fluorescent in situ hybridization (FISH) assays. O6-methylguanine-DNA methyltransferase (MGMT) gene promoter methylation and Isocitrate dehydrogenase 1 (IDH1) mutation status were also assessed. All samples were interpreted by two experienced pathologists who were blinded to the clinical data. A total of 109 samples were collected and all samples were examined for ROS1 rearrangement by IHC and FISH assays, and none was found to harbor ROS1 rearrangement. MGMT gene methylation was found in 42 (39.2%) cases, and IDH1 mutation was found in 6 (5.5%) cases. In this study, ROS1 rearrangement was not identified in GBM patients, and thus it is difficult to classify ROS1 rearrangement as a novel molecular subset in GBM patients for now. PMID- 26366869 TI - Correction: Homogentisate 1-2-Dioxygenase Downregulation in the Chronic Persistence of Pseudomonas aeruginosa Australian Epidemic Strain-1 in the CF Lung. PMID- 26366868 TI - Differential Expression of Non-Shelterin Genes Associated with High Telomerase Levels and Telomere Shortening in Plasma Cell Disorders. AB - Telomerase, shelterin proteins and various interacting factors, named non shelterin proteins, are involved in the regulation of telomere length (TL). Altered expression of any of these telomere-associated genes can lead to telomere dysfunction, causing genomic instability and disease development. In this study, we investigated the expression profile of a set of non-shelterin genes involved in essential processes such as replication (RPA1), DNA damage repair pathways (MRE11-RAD50-NBS1) and stabilization of telomerase complex (DKC1), in 35 patients with monoclonal gammopathy of undetermined significance (MGUS) and 40 cases with multiple myeloma (MM). Results were correlated with hTERT expression, TL and clinical parameters. Overall, a significant increase in DKC1, RAD50, MRE11, NBS1 and RPA1 expression along with an upregulation of hTERT in MM compared with MGUS was observed (p<=0.032). Interestingly, in both entities high mRNA levels of non shelterin genes were associated with short TLs and increased hTERT expression. Significant differences were observed for DKC1 in MM (p <=0.026), suggesting an important role for this gene in the maintenance of short telomeres by telomerase in myeloma plasma cells. With regard to clinical associations, we observed a significant increase in DKC1, RAD50, MRE11 and RPA1 expression in MM cases with high bone marrow infiltration (p<=0.03) and a tendency towards cases with advanced ISS stage, providing the first evidence of non-shelterin genes associated to risk factors in MM. Taken together, our findings bring new insights into the intricate mechanisms by which telomere-associated proteins collaborate in the maintenance of plasma cells immortalization and suggest a role for the upregulation of these genes in the progression of the disease. PMID- 26366870 TI - Defects of the Lamina Cribrosa in High Myopia and Glaucoma. AB - PURPOSE: We evaluated the prevalence and characteristics of the defects of the lamina cribrosa (LC) in high myopia and glaucoma, and compared them with control eyes using swept-source optical coherence tomography (SS-OCT). METHODS: One hundred fifty-nine eyes of 108 participants were divided into four subgroups; high myopia with glaucoma (MG, 67 eyes of 46 subjects), glaucoma without high myopia (G, 22 eyes of 13 subjects), high myopia without glaucoma (M, 35 eyes of 29 subjects), and a control group with neither glaucoma nor high myopia (C, 35 eyes of 20 subjects). The LC defects were identified and located using a standardized protocol in serial horizontal OCT scans. The prevalence rates of the defects were compared among the groups. Demographic and ocular factors were compared between eyes with and without defects. RESULTS: LC defects were observed in one eye (0.03%) in the C group, 8 eyes (22.9%) in the M group, 11 eyes (50%) in the G group, and 28 eyes (41.8%) in the MG group. The prevalence rates of the defects differed significantly among the groups (P = 0.0009). Most eyes with defects in the G and MG groups (79.5%) had damage in the corresponding visual hemifields. Other factors such as visual acuity, intraocular pressure, axial length, refractive error, disc ovality, or parapapillary atrophy area did not differ significantly between eyes with and without LC defects. CONCLUSIONS: High myopia and glaucoma significantly increased the risk of LC damage. The LC damage in non-glaucomatous highly myopic eyes may at least partly explain the increased risk of developing glaucoma in myopic eyes. PMID- 26366871 TI - GeneXpert MTB/RIF Assay for the Diagnosis of Tuberculous Lymphadenitis on Concentrated Fine Needle Aspirates in High Tuberculosis Burden Settings. AB - INTRODUCTION: The diagnosis of tuberculous lymphadenitis (TBL) remains challenging. The routinely used methods (cytology and smear microscopy) have sub optimal sensitivity. Recently, WHO recommends GeneXpert to be used as the initial diagnostic test in patients suspected of having extra-pulmonary tuberculosis (EPTB). However, this was a conditional recommendation due to very low-quality evidence available and more studies are needed. In this study we evaluated the performance of Xpert for the diagnosis of TBL on concentrated fine needle aspirates (FNA) in Southwest Ethiopia. METHODS: FNA was collected from presumptive TBL cases. Two smears were prepared from each aspirate and processed for cytology and conventional microscopy. The remaining aspirate was treated with N-acetyl-L-cysteine-NaOH and centrifuged for 15minutes at 3000g. The concentrated sediment was used for culture and Xpert test. Capilia TB-Neo test was used to differentiate M. tuberculosis complex (MTBC) from non-tuberculous mycobacteria (NTM). Composite bacteriological methods (culture and/or smear microscopy) were considered as a reference standard. RESULT: Out of 143 enrolled suspects, 64.3% (92/143) were confirmed TBL cases by the composite reference standard (CRS). Xpert detected M. tuberculosis complex (MTBC) in 60.1% (86/143) of the presumptive TBL cases. The sensitivity of Xpert compared to CRS was 87.8% [95% CI: 81.0-94.5] and specificity 91.1% [95% CI: 82.8-99.4]. The sensitivity was 27.8% for smear microscopy and 80% for cytology compared to CRS. Cytology showed the lowest specificity (57.8%). Xpert was positive in 4 out of 45 culture- and smear-negative cases. Among 47 cytomorphologically non-TBL cases, 15 were positive on Xpert. More than half of Xpert-positive cases were in the range of very low cut-off threshold values (28RS = SR>SS) > fluvastatin (SR>RS = SS>RR) >> rosuvastatin (only RS active). The data presented here might be of toxicological and clinical importance. PMID- 26366875 TI - Comment on Gautheret-Dejean et al.: Performance of rapid tests for discrimination between HIV-1 and/or HIV-2 infections. PMID- 26366874 TI - Re-assess Vector Indices Threshold as an Early Warning Tool for Predicting Dengue Epidemic in a Dengue Non-endemic Country. AB - BACKGROUND: Despite dengue dynamics being driven by complex interactions between human hosts, mosquito vectors and viruses that are influenced by climate factors, an operational model that will enable health authorities to anticipate the outbreak risk in a dengue non-endemic area has not been developed. The objectives of this study were to evaluate the temporal relationship between meteorological variables, entomological surveillance indices and confirmed dengue cases; and to establish the threshold for entomological surveillance indices including three mosquito larval indices [Breteau (BI), Container (CI) and House indices (HI)] and one adult index (AI) as an early warning tool for dengue epidemic. METHODOLOGY/PRINCIPAL FINDINGS: Epidemiological, entomological and meteorological data were analyzed from 2005 to 2012 in Kaohsiung City, Taiwan. The successive waves of dengue outbreaks with different magnitudes were recorded in Kaohsiung City, and involved a dominant serotype during each epidemic. The annual indigenous dengue cases usually started from May to June and reached a peak in October to November. Vector data from 2005-2012 showed that the peak of the adult mosquito population was followed by a peak in the corresponding dengue activity with a lag period of 1-2 months. Therefore, we focused the analysis on the data from May to December and the high risk district, where the inspection of the immature and mature mosquitoes was carried out on a weekly basis and about 97.9% dengue cases occurred. The two-stage model was utilized here to estimate the risk and time-lag effect of annual dengue outbreaks in Taiwan. First, Poisson regression was used to select the optimal subset of variables and time-lags for predicting the number of dengue cases, and the final results of the multivariate analysis were selected based on the smallest AIC value. Next, each vector index models with selected variables were subjected to multiple logistic regression models to examine the accuracy of predicting the occurrence of dengue cases. The results suggested that Model-AI, BI, CI and HI predicted the occurrence of dengue cases with 83.8, 87.8, 88.3 and 88.4% accuracy, respectively. The predicting threshold based on individual Model-AI, BI, CI and HI was 0.97, 1.16, 1.79 and 0.997, respectively. CONCLUSION/SIGNIFICANCE: There was little evidence of quantifiable association among vector indices, meteorological factors and dengue transmission that could reliably be used for outbreak prediction. Our study here provided the proof-of-concept of how to search for the optimal model and determine the threshold for dengue epidemics. Since those factors used for prediction varied, depending on the ecology and herd immunity level under different geological areas, different thresholds may be developed for different countries using a similar structure of the two-stage model. PMID- 26366876 TI - Electron energy loss spectroscopy on semiconductor heterostructures for optoelectronics and photonics applications. AB - In this work, we present characterization methods for the analysis of nanometer sized devices, based on silicon and III-V nitride semiconductor materials. These methods are devised in order to take advantage of the aberration corrected scanning transmission electron microscope, equipped with a monochromator. This set-up ensures the necessary high spatial and energy resolution for the characterization of the smallest structures. As with these experiments, we aim to obtain chemical and structural information, we use electron energy loss spectroscopy (EELS). The low-loss region of EELS is exploited, which features fundamental electronic properties of semiconductor materials and facilitates a high data throughput. We show how the detailed analysis of these spectra, using theoretical models and computational tools, can enhance the analytical power of EELS. In this sense, initially, results from the model-based fit of the plasmon peak are presented. Moreover, the application of multivariate analysis algorithms to low-loss EELS is explored. Finally, some physical limitations of the technique, such as spatial delocalization, are mentioned. PMID- 26366877 TI - A handmaiden to science: the role of the editor in psychiatric research. PMID- 26366878 TI - Correction: Insights into Sexism: Male Status and Performance Moderates Female Directed Hostile and Amicable Behaviour. PMID- 26366879 TI - Eshelby Twist as a Possible Source of Lattice Rotation in a Perfectly Ordered Protein/Silica Structure Grown by a Simple Organism. AB - The formation mechanism of a perfectly ordered protein/silica structure in the axial filament of the anchor spicule of the silica sponge Monorhaphis chuni is suggested. Experimental evidence shows that the growth of this architecture is realized by a thermodynamically driven dislocation-mediated spiral growth mechanism, resulting in a specific rotation of the mesoscopic crystal lattice (Eshelby twist). PMID- 26366880 TI - The Internal Dynamics of Fibrinogen and Its Implications for Coagulation and Adsorption. AB - Fibrinogen is a serum multi-chain protein which, when activated, aggregates to form fibrin, one of the main components of a blood clot. Fibrinolysis controls blood clot dissolution through the action of the enzyme plasmin, which cleaves fibrin at specific locations. Although the main biochemical factors involved in fibrin formation and lysis have been identified, a clear mechanistic picture of how these processes take place is not available yet. This picture would be instrumental, for example, for the design of improved thrombolytic or anti haemorrhagic strategies, as well as, materials with improved biocompatibility. Here, we present extensive molecular dynamics simulations of fibrinogen which reveal large bending motions centered at a hinge point in the coiled-coil regions of the molecule. This feature, likely conserved across vertebrates according to our analysis, suggests an explanation for the mechanism of exposure to lysis of the plasmin cleavage sites on fibrinogen coiled-coil region. It also explains the conformational variability of fibrinogen observed during its adsorption on inorganic surfaces and it is supposed to play a major role in the determination of the hydrodynamic properties of fibrinogen. In addition the simulations suggest how the dynamics of the D region of fibrinogen may contribute to the allosteric regulation of the blood coagulation cascade through a dynamic coupling between the a- and b-holes, important for fibrin polymerization, and the integrin binding site P1. PMID- 26366881 TI - A New Sandwich ELISA for Quantification of Thymidine Kinase 1 Protein Levels in Sera from Dogs with Different Malignancies Can Aid in Disease Management. AB - Thymidine kinase 1 (TK1) is a DNA precursor enzyme whose expression is closely correlated with cell proliferation and cell turnover. Sensitive serum TK1 activity assays have been used for monitoring and prognosis of hematological malignancies in both humans and dogs. Here we describe the development of a specific sandwich TK1-ELISA for the quantification of TK1 protein levels in sera from dogs with different malignancies. A combination of rabbit polyclonal anti dog TK1 antibody and a mouse monoclonal anti-human TK1 antibody was used. Different concentrations of recombinant canine TK1 was used as standard. Clinical evaluation of the ELISA was done by using sera from 42 healthy dogs, 43 dogs with hematological tumors and 55 with solid tumors. An established [3H]-dThd phosphorylation assay was used to determine the TK1 activity levels in the same sera. The mean TK1 activities in dogs with hematological tumors were significantly higher than those found in healthy dogs. In agreement with earlier studies, no significant difference was observed in serum TK1 activities between healthy dogs and dogs with solid tumors. However, the mean TK1 protein levels determined by new TK1-ELISA were significantly higher not only in hematological tumors but also in solid tumors compared to healthy dogs (mean +/- SD = 1.30 +/- 1.16, 0.67 +/- 0.55 and 0.27+/- 0.10 ng/mL, respectively). Moreover, TK1-ELISA had significantly higher ability to distinguish lymphoma cases from healthy based on receiver operating characteristic analyses (area under the curve, AUC, of 0.96) to that of the activity assay (AUC, 0.84). Furthermore, fluctuations in TK1 protein levels during the course of chemotherapy in dogs with lymphoma closely associated with clinical outcome. Overall, the TK1-ELISA showed significant linear correlation with the TK1 activity assay (rs = 0.6, p<0.0001). Thus, the new TK1-ELISA has sufficient sensitivity and specificity for routine clinical use in veterinary oncology. PMID- 26366882 TI - Designing Light-Activated Charge-Separating Proteins with a Naphthoquinone Amino Acid. AB - The first principles design of manmade redox-protein maquettes is used to clarify the physical/chemical engineering supporting the mechanisms of natural enzymes with a view to recapitulate and surpass natural performance. Herein, we use intein-based protein semisynthesis to pair a synthetic naphthoquinone amino acid (Naq) with histidine-ligated photoactive metal-tetrapyrrole cofactors, creating a 100 MUs photochemical charge separation unit akin to photosynthetic reaction centers. By using propargyl groups to protect the redox-active para-quinone during synthesis and assembly while permitting selective activation, we gain the ability to employ the quinone amino acid redox cofactor with the full set of natural amino acids in protein design. Direct anchoring of quinone to the protein backbone permits secure and adaptable control of intraprotein electron-tunneling distances and rates. PMID- 26366883 TI - Rapid SERS monitoring of lipid-peroxidation-derived protein modifications in cells using photonic crystal fiber sensor. AB - We proposed a side channel photonic crystal fiber (SC-PCF) based Surface enhanced Raman spectroscopy (SERS) platform which is able to accurately monitor lipid peroxidation derived protein modifications in cells. This platform incorporates linoleamide alkyne (LAA), which is oxidized and subsequently modifies proteins in cells with alkyne functional group upon lipid peroxidation. By loading the side channel of SC-PCF with a mixture of gold nanoparticles and LAA treated cells, and subsequently measuring the interference-free alkyne Raman peak from these proteins in cells, strong SERS signal was obtained. The platform provides a method for the rapid monitoring of lipid peroxidation derived protein modification in cells. PMID- 26366884 TI - Coping Self-Efficacy Moderates the Association Between Severity of Partner Violence and PTSD Symptoms Among Incarcerated Women. AB - Previous research indicates self-efficacy may function as a protective factor for survivors of partner violence (PV), including coping self-efficacy specific to domestic violence. We hypothesized that domestic violence coping self-efficacy would moderate the association between recent PV and posttraumatic stress disorder (PTSD) symptoms in a sample of incarcerated women, such that the association between PV and PTSD would be strongest at low levels of domestic violence coping self-efficacy. Participants (N = 102) were incarcerated women who reported PV in the year prior to incarceration. They were aged 19-55 years (M = 33.57, SD = 9.32), identified predominantly as European American (84.3%), American Indian (15.7%), and Hispanic (14.7%), with 80.4% completing high school or more in terms of education. Participants responded to self-report measures of PV, trauma history, domestic violence coping self-efficacy, and current PTSD symptoms. In a series of sequential regression analyses, PV (beta = .65, sr(2) = .06, p = .017) was significantly associated with current PTSD symptoms above and beyond past trauma history (beta = .37, sr(2) = .14, p < .001), and this association was moderated by domestic violence coping self-efficacy (Domestic Violence Coping Self-Efficacy * Partner Violence; beta = -.54, sr(2) = .03, p = .044). The relationship between PV and PTSD symptoms was greatest at low and average levels of domestic violence coping self-efficacy and nonsignificant at high levels of domestic violence coping self-efficacy. These findings highlight the importance of assessing domestic violence coping self-efficacy in incarcerated women with recent PV, given that domestic violence coping self efficacy appeared to be protective against symptoms of PTSD. PMID- 26366885 TI - Stating Appointment Costs in SMS Reminders Reduces Missed Hospital Appointments: Findings from Two Randomised Controlled Trials. AB - BACKGROUND: Missed hospital appointments are a major cause of inefficiency worldwide. Healthcare providers are increasingly using Short Message Service reminders to reduce 'Did Not Attend' (DNA) rates. Systematic reviews show that sending such reminders is effective, but there is no evidence on whether their impact is affected by their content. Accordingly, we undertook two randomised controlled trials that tested the impact of rephrasing appointment reminders on DNA rates in the United Kingdom. TRIAL METHODS: Participants were outpatients with a valid mobile telephone number and an outpatient appointment between November 2013 and January 2014 (Trial One, 10,111 participants) or March and May 2014 (Trial Two, 9,848 participants). Appointments were randomly allocated to one of four reminder messages, which were issued five days in advance. Message assignment was then compared against appointment outcomes (appointment attendance, DNA, cancellation by patient). RESULTS: In Trial One, a message including the cost of a missed appointment to the health system produced a DNA rate of 8.4%, compared to 11.1% for the existing message (OR 0.74, 95% CI 0.61 0.89, P<0.01). Trial Two replicated this effect (DNA rate 8.2%), but also found that expressing the same concept in general terms was significantly less effective (DNA rate 9.9%, OR 1.22, 95% CI 1.00-1.48, P<0.05). Moving from the existing reminder to the more effective costs message would result in 5,800 fewer missed appointments per year in the National Health Service Trust in question, at no additional cost. The study's main limitations are that it took place in a single location in England, and that it required accurate phone records, which were only obtained for 20% of eligible patients. We conclude that missed appointments can be reduced, for no additional cost, by introducing persuasive messages to appointment reminders. Future studies could examine the impact of varying reminder messages in other health systems. TRIAL REGISTRATION: Controlled Trials.com 49432571. PMID- 26366886 TI - A RANDOMIZED CONTROLLED TRIAL IN COMMUNITY MENTAL HEALTH CENTERS OF COMPUTER ASSISTED COGNITIVE BEHAVIORAL THERAPY VERSUS TREATMENT AS USUAL FOR CHILDREN WITH ANXIETY. AB - OBJECTIVE: This study aims to examine the real-world effectiveness of a computer assisted cognitive behavioral therapy (CBT) protocol relative to treatment as usual (TAU) among anxious children presenting at community mental health centers. METHODS: One hundred children (7-13 years) with clinically significant anxiety were randomized to receive either 12 weekly computer-assisted CBT sessions or TAU for an equivalent duration. Assessments were conducted by independent evaluators at screening/baseline, midtreatment, posttreatment, and 1-month followup (for computer-assisted CBT treatment responders). RESULTS: There were significant between-group effects favoring the computer-assisted CBT condition on primary anxiety outcomes. Thirty of 49 (61.2%) children randomized to computer-assisted CBT responded to treatment, which was superior to TAU (6/51, 11.8%). Relative to TAU, computer-assisted CBT was associated with greater reductions in parent-rated child impairment and internalizing symptoms, but not child-rated impairment and anxiety and depressive symptoms. Treatment satisfaction and therapeutic alliance in those receiving computer-assisted CBT was high. Treatment gains in computer assisted CBT responders were maintained at 1-month followup. CONCLUSIONS: Within the limitations of this study, computer-assisted CBT is an effective and feasible treatment for anxious children when used in community mental health centers by CBT-naive clinicians. PMID- 26366887 TI - Recent Progress in Using Biomaterials as Vitreous Substitutes. AB - Vitreous substitutes are crucial adjuncts during vitreo-retinal surgery for retinal diseases such as complicated retinal detachment, macular holes, complications of diabetic retinopathy, and ocular trauma involving posterior segment. In retinal detachment surgery, an internal tamponade agent is required to provide internal pressure for reattachment of the detached neurosensory retina. Current available options serve only as a temporary surgical adduct or short-term solution and are associated with inherent problems. Despite many years of intensive research, an ideal vitreous substitute remains elusive. Indeed, the development of an ideal vitreous substitute requires the concerted efforts of synthetic chemists and biomaterial engineers, as well as ophthalmic surgeons. In this review, we propose that polymeric hydrogels present the future of artificial vitreous substitutes due to its high water composition, optical transparency, and rheological properties that closely mimic the natural vitreous. In particular, thermosensitive smart hydrogels, with reversible sol to gel change, have emerged as the material class with the most potential to succeed as ideal vitreous substitutes, facilitating easy implementation during surgery. Importantly, these smart hydrogels also display potential as efficacious drug delivery systems. PMID- 26366888 TI - Effectiveness of Polyglycolic Acid Sheet Covering and Platelet-Rich Plasma after Video-Assisted Thoracic Surgery for Spontaneous Pneumothorax. AB - Background Video-assisted thoracic surgery (VATS) is widely used for the treatment of spontaneous pneumothorax, and the recurrence rate is high. The goal of the study was to examine the use of polyglycolic acid (PGA) sheets, together with platelet-rich plasma (PRP) from autologous blood for the prevention of postoperative recurrence of spontaneous pneumothorax. Materials and Methods We performed a retrospective study of 65 patients who underwent VATS for spontaneous pneumothorax from March 2008 to November 2011. The patients were divided into groups: without reinforcement (Group A, n = 33) and with reinforcement of the visceral pleura around the staple lines with the PGA sheet and PRP (Group B, n = 32). The postoperative follow-up period was 18 months. Results Chest tubes were used for 3.4 and 3.1 days in Groups A and B, respectively, with no significant difference between the groups. However, the recurrence rate (18.2%; 6 cases) in Group A was significantly higher than that in Group B (p = 0.02). The recurrence rates in patients younger than 25 years in Group A and Group B were 26.1 and 0.0%, respectively (p = 0.03). In Group A, the mean age with recurrence (18.3 years old) was significantly lower than the mean age without recurrence (p = 0.03). Conclusion These results suggest that the use of PGA sheets and PRP might be effective for the prevention of postoperative recurrence of spontaneous pneumothorax. PMID- 26366889 TI - Safety and Feasibility of Induction Immunosuppression When Driveline Infection Is an Indication for Cardiac Transplantation. AB - BACKGROUND: There is a paucity of data on the use of induction immunosuppression in patients with active infections undergoing orthotopic heart transplantation (OHT). We hypothesized that induction immunosuppression in patients with ventricular assist device (VAD) undergoing OHT with localized active driveline infection (DLI) does not lead to worse outcomes. MATERIALS AND METHODS: We retrospectively analyzed our database for bridge-to-transplant VAD patients who underwent OHT and received induction therapy. Patients were stratified into those with and without active DLI at the time of OHT and followed up till death or at least 30 months after OHT. Posttransplant length of stay (LOS), frequency of infections, and mortality were compared between the two groups. RESULTS: Thirty eight patients (30 males) with mean age of 57.5 +/- 13 years with VAD underwent OHT during the study period. Twelve had active DLI. Mean follow-up was 46.4 +/- 23.1 months. In the DLI versus non-DLI group, there was no difference in mortality (17 vs. 23%, p = NS), LOS (16.3 +/- 5.4 vs. 17.2 +/- 13.7, p = NS), postoperative renal function, incidence of hyperacute or late rejection or infection either in the first month (25 vs. 23%, p = NS) or during entire follow up (92 vs. 88%, p = NS). No patient in the DLI group had infections attributable to the same organism responsible for pretransplant DLI. CONCLUSION: In patients with active DLI, induction immunosuppression after OHT did not increase LOS, infections, or mortality after at least 30 months of follow-up and therefore it appears to be a safe and feasible therapeutic option. PMID- 26366890 TI - Vasopressinase Activity: A Potential Early Biomarker for Detecting Cardiopulmonary Bypass-Associated Acute Kidney Injury? AB - Background Acute kidney injury (AKI) is a common and serious complication of surgeries that include cardiopulmonary bypass (CPB). Currently, increases in serum creatinine levels are used to diagnose AKI, but this change may be slow to detect. Animal studies pertaining to renal hypoxia suggest a correlation between vasopressinase activity and AKI. The objective of this study is to determine if vasopressinase activity can be used as an early biomarker for renal hypoxia and CPB-associated AKI. This could potentially help improve the diagnosis and subsequent treatment of the condition. Materials and Methods We conducted a single-center, prospective observational study which analyzed serum vasopressinase activity and creatinine levels at seven time points from 31 patients undergoing CPB. We also measured urine vasopressinase activity in 19 of the 31 patients at five of the time points. Results Results show that serum and urine vasopressinase activity peak at the time of arrival to the ICU for patients undergoing CPB. This increase occurred earlier than the increase in creatinine, which generally occurred on postoperative day 2. In the five patients who were diagnosed with AKI, vasopressinase activity peaked 30 minutes into CPB while creatinine peaked on postoperative day 2. Conclusion Our findings suggest that vasopressinase might be a potential early biomarker for AKI. Further studies with other AKI biomarkers are required to determine if the vasopressinase response can be directly attributed to the presence of AKI. PMID- 26366892 TI - Method of field expansions for vector electromagnetic scattering by layered periodic crossed gratings. AB - In many applications of scientific and engineering interest the accurate modeling of scattering of linear waves by periodic layered media plays a crucial role. From geophysics and oceanography to materials science and imaging, the ability to simulate such configurations numerically in a rapid and robust fashion is of paramount importance. In this contribution we focus upon the specific problem of vector electromagnetic radiation interacting with a multiply layered periodic crossed diffraction grating. While all of the classical methods for the numerical simulation of partial differential equations have been brought to bear upon this problem, we argue here that in this particular context a high-order perturbation of surfaces approach is superior. In particular, we describe how the method of field expansions can be extended to the fully vectorial and three-dimensional scattering problem in the presence of multiple layers. With specific numerical experiments we will show the remarkable efficiency, fidelity, and high-order accuracy one can achieve with an implementation of this algorithm. PMID- 26366893 TI - Derivatives of optical path length: from mathematical formulation to applications. AB - The optical path length (OPL) of an optical system is a highly important parameter since it determines the phase of the light passing through the system and governs the interference and diffraction of the rays as they propagate. The Jacobian and Hessian matrices of the OPL are of fundamental importance in tuning the performance of a system. However, the OPL varies as a recursive function of the incoming ray and the boundary variable vector, and hence computing the Jacobian and Hessian matrices is extremely challenging. In an earlier study by the present group, this problem was addressed by deriving the Jacobian matrix of the OPL with respect to all of the independent system variables of a nonaxially symmetric system. In the present study, the proposed method is extended to the Hessian matrix of a nonaxially symmetric optical system. The proposed method facilitates the cross-sensitivity analysis of the OPL with respect to arbitrary system variables and provides an ideal basis for automatic optical system design applications in which the merit function is defined in terms of wavefront aberrations. An illustrative example is given. It is shown that the proposed method requires fewer iterations than that based on the Jacobian matrix and yields a more reliable and precise optimization performance. PMID- 26366891 TI - Gender Differences in Long-Term Survival after Surgery for Non-Small Cell Lung Cancer. AB - Background This retrospective study examined gender differences in non-small cell lung cancer (NSCLC) by analyzing surgical cases at a single institution. Patients and Methods In this study, 735 NSCLC patients who underwent surgery from 1995 to 2010 were included. Clinical and pathological characteristics were retrieved by reviewing charts retrospectively, and variables between genders were compared. Results There were 489 males and 246 females in the study. The percentage of screening-detected lung cancers (83.7%), never smokers (82.9%), adenocarcinoma histology (90.7%), and pathological stage IA (42.7%) was higher in females than that in males (71.2, 8.2, 51.3, and 23.1%, respectively). Female patients had fewer cases of coronary artery disease (2.8%) and fewer pneumonectomy cases (2.0%) than the male patients (7.4 and 5.3%, respectively). The median follow-up period after surgery was 5.9 years. The overall survival rates at 5 years were 57.3% for males and 76.2% for females (p < 0.001, log-rank test). Based on univariate analysis, we report that histology, smoking history, and pathological stage were significant prognostic factors in addition to gender. Based on multivariate analysis, pathological stage III/IV (hazard ratio, 3.60; 95% confidence interval [CI], 2.84-4.54) and female gender (hazard ratio, 0.55; 95% CI, 0.37-0.82) were significant prognostic factors. Subgroup analysis demonstrated that female gender and adenocarcinoma histology were significant positive prognostic factors only in pathological stages I and II (n = 557). Conclusion Female gender as well as pathological stage was favorable prognostic factors. The survival advantage observed in female NSCLC patients was limited to those with cancer at stages I and II. PMID- 26366894 TI - Effective degree of coherence: a second look. AB - In this paper, we show that the most general set of transformations of electromagnetic fields, for which overall (global) second-order coherence properties can reasonably be expected to remain unchanged, is the set of scaled unitary transformations. Building on our earlier results concerning coherence functionals that are invariant to scaled unitary transformations, we prove that the effective degree of coherence is the only such functional that is "additive" in the sense that it can be computed for linear combinations of fields from its values for pairwise sums of the constituent fields. Additionally, we highlight the fact that the invariance of the effective degree of coherence to scaled unitary transformations means that it has the same value when computed from most of the important representations of electromagnetic fields. We then go on to use the effective degree of coherence to provide a generalization of the scalar two point degree-of-coherence function to a system consisting of two orthogonal Hilbert spaces. Interestingly, several commonly used measures of coherence and polarization turn out to be special cases of this generalization. PMID- 26366895 TI - Reduced-order spectral data modeling based on local proper orthogonal decomposition. AB - Spectral imaging typically generates a large amount of high-dimensional data that are acquired in different sub-bands for each spatial location of interest. The high dimensionality of spectral data imposes limitations on numerical analysis. As such, there is an emerging demand for robust data compression techniques with loss of less relevant information to manage real spectral data. In this paper, we describe a reduced-order data modeling technique based on local proper orthogonal decomposition (POD) in order to compute low-dimensional models by projecting high dimensional clusters onto subspaces spanned by local reduced-order bases. We refer to the proposed method as the local-based approach because POD finds locally optimal solutions on each group split by k-means clustering. Experimental results are reported on three public domain databases and an in-house database. Comparisons with three leading spectral recovery techniques, three decomposition techniques used for hyperspectral imaging, and two baseline techniques show that the proposed method leads to promising improvement on spectral and colorimetric accuracy corresponding to the reconstructed spectral reflectance. PMID- 26366896 TI - Statistical similarity and complete coherence of electromagnetic fields in time and frequency domains. AB - We investigate the statistical similarity of partially polarized, partially coherent electromagnetic fields in time and frequency domains, and the relationship between statistical similarity and complete coherence. We find that, both in time domain and frequency domain, the complete coherence of two fields is equivalent to the fields being both fully polarized and statistically similar. Unlike in scalar coherence theory, statistical similarity alone is found not to constitute a sufficient condition for complete coherence. We derive the conditions under which spectrally completely coherent fields are also temporally fully coherent, and we point out that temporally completely coherent fields are necessarily fully spectrally coherent at all frequencies. Complete temporal and spectral coherence of electromagnetic fields are found to be related to the recently introduced concept of strict cross-spectral purity, but in contrast to the scalar case, strict cross-spectral purity is not a necessary condition for complete temporal coherence if the fields have different spectral polarization states. PMID- 26366897 TI - Expansion of the difference-field boundary element method for numerical analyses of various local defects in periodic surface-relief structures. AB - We expand the difference-field boundary element method (DFBEM) to calculate wave scattering from a variety of local periodic structure defects. The DFBEM is a numerical method for simulating the diffraction caused by a periodic surface relief structure with a defect. Although it is more efficient than conventional techniques such as the finite-difference time-domain (FDTD) method, the original DFBEM is limited to projection defects. Here, we derive the integral equations and expressions for crack and buried-pillar defects, and also demonstrate some numerical analyses, validating the results by comparison with results from the FDTD method and the dielectric interface boundary conditions. PMID- 26366898 TI - Experimental investigation of circular Bragg phenomenon for oblique incidence. AB - A 20-period-thick chiral sculptured thin film (STF) of zinc selenide was fabricated on a glass slide by thermal evaporation. A variable-angle spectroscopic system was devised and used to measure all eight of the circular remittances of the chiral STF as functions of the angle of incidence and the free space wavelength. Thereby, the center wavelength and the bandwidth of the circular Bragg phenomenon exhibited by structurally chiral materials such as cholesteric liquid crystals and chiral STFs were comprehensively characterized for incidence angles in the range [0 degrees ,70 degrees ]. The experimental data were qualitatively compared with data calculated using a helicoidal model for the relative permittivity dyadic of the chiral STF, and assuming that all three eigenvalues of that dyadic obey the single-resonance Lorentz model. The chosen representation was found adequate to represent the blue shift of the centerwavelength with an increasing angle of incidence, but the Lorentz model requires modification to develop improved predictive capabilities. PMID- 26366899 TI - Compact interferometer transducer based on surface plasmon phase resonance. AB - We propose a new monolithic interferometric configuration and implement a novel method for spectroscopic phase shift detection of surface plasmon resonance (SPR) sensors. The interference pattern is obtained using a nonpolarizing beam splitter cube with two attached right angle prisms in such a way that each interference field undergoes two total internal reflections (TIR) at prisms/air interface and one attenuated total reflection (ATR) through surface plasmon interaction. The evanescent part of the interferogram around the Zero optical path difference (ZOPD) is sampled and detected in the far field, thanks to a bidimensional array of scattering optical near-field probes deposited on the corresponding prism surface. A Fourier transform of the sampled interferogram is performed to measure the input light wavelength, while a direct comparison of the interferogram in TM and TE polarization modes allows us to determine the differential phase shift induced by the SPR layer. The phase shift measurement is made possible thanks to a remarkable time stability of the interferogram in the glass bulk. By tuning the input laser wavelength around the resonance, we show a good agreement between experimental and theoretical calculations for both amplitude and phase spectral responses. PMID- 26366900 TI - Broadband optical isolator based on helical metamaterials. AB - Based on helical metamaterials, a new broadband optical isolator with a triple helix structure is proposed in this paper. The right-handed circularly polarized light can transmit through the isolator with its polarization unchanged. The reverse propagating light, which is caused by the reflection of the latter optical devices, is converted into left-handed circularly polarized light that is suppressed by the proposed isolator because of absorption. Our design has some unprecedented advantages such as broad frequency ranges and a compact structure; moreover, neither polarizers nor adscititious magnetic fields are required. Properties of the isolator are investigated using the finite-difference time domain method, and this phenomenon is studied by the mechanism of helical antenna theory. PMID- 26366901 TI - Dyakonov hybrid surface waves at the isotropic-biaxial media interface. AB - Dyakonov surface waves (DSWs) at the interface of an isotropic dielectric material and a biaxial dielectric crystal were considered in the case in which two principal axes of the biaxial crystal lie in the plane of the interface. Both x-cut and y-cut biaxial crystals were considered, and all permittivity scalars were assumed to be real and positive. A rather simple expression to relate the components of the wave vector of a DSW was derived, and analytical expressions for the limit angles at which the DSWs can propagate and the Poynting vector components of the DSWs were obtained. These expressions were numerically investigated for several biaxial materials. Different conditions for the relative permittivity scalars at which the DSWs can exist were identified. As an example, DSWs can exist not only for the positive, but also for the negative y-cut biaxial crystals. PMID- 26366902 TI - Shape-invariant difference between two Gaussian Schell-model beams. AB - The difference between two Gaussian Schell-model cross-spectral densities can give a new genuine correlation function if suitable conditions are met. Generally speaking, the structure of such cross-spectral density changes in a complicated way upon propagation. We consider here the notable exception of shape-invariant beams, and we investigate their intensity and coherence properties. The modal analysis of this class of cross-spectral densities is exploited to devise a synthesis scheme for this type of beam. PMID- 26366903 TI - Radiation forces on a Rayleigh particle by highly focused radially polarized beams modulated by DVL. AB - The intensity and the radiation forces acting on a Rayleigh particle near the focus of completely coherent radially polarized beams whose phase are modulated by a devil's vortex-lens (DVL) are studied. The influence of the structure of a DVL on the radiation force distribution is analyzed. It is found by numerical simulations that the modulated beams show a clear advantage over the unmodulated highly focused radially polarized beams, as the modulated beam can simultaneously trap and manipulate the multiple Rayleigh particles, while the unmodulated beam can trap only one particle under the same condition. PMID- 26366904 TI - Electrically variable liquid crystal lens based on the dielectric dividing principle. AB - Theoretical modeling is performed for a liquid crystal (LC) lens that uses a combination of two dielectric lenses and voltage dividing principle to shape the electric field in space. Electric field, LC reorientation, and optical phase retardation profiles are obtained by numerical simulations. The obtained results are compared with experimental ones, and good agreement is obtained validating the proposed two-dimensional model that uses a limited number of dielectric and geometrical control parameters for this type of lens. PMID- 26366905 TI - Noise cancellation with phase-detection technique for pump-probe measurement and application to stimulated Raman imaging. AB - Intensity noise on a probe beam is a serious obstacle to highly sensitive and high-speed pump-probe microscopy. In this report, a reference beam of the probe is prepared and delayed. The intensity modulation by the sample is measured as the phase modulation of the superposition of detected electrical signals of the probe and reference beams, and the intensity noise is canceled. We evaluate performance of the noise cancellation using the super-continuum light from a piece of photonic crystal fiber, and find that the noise is canceled by ~26 dB. We then apply the method to a stimulated Raman microscope. This method contributes to highly sensitive and high-speed pump-probe imaging with various light sources. PMID- 26366906 TI - Nodal aberration properties of coaxial imaging systems using Zernike polynomial surfaces. AB - As a combination of the nodal aberration theory (NAT) and the freeform surface optical design, the nodal aberration properties of Zernike polynomial surfaces in a coaxial imaging system are analyzed in detail in this paper. The aberrations induced by the Zernike polynomial terms on either the reflective or the refractive surfaces in the system can be quantitatively calculated, which can be used to predict the surface figure or mount-induced errors, or as guidance for aberration correction and optimization during the freeform optical design. Specially, some new kinds of aberrations with complex field dependence can be generated by the Zernike polynomial terms, which further lead to the discovery of linear or multilinear nodes (cruciate nodes) in the aberration field. This linear nodal property will benefit the design of some kinds of freeform optical systems with a linear field of view. Furthermore, an iterative method based on the NAT is proposed to correct the field-constant aberrations. PMID- 26366907 TI - Evolution of phase singularities of vortex beams propagating in atmospheric turbulence. AB - Optical vortex beams propagating through atmospheric turbulence are studied by numerical modeling, and the phase singularities of the vortices existing in the turbulence-distorted beams are calculated. It is found that the algebraic sum of topological charges (TCs) of all the phase singularities existing in test aperture is approximately equal to the TC of the input vortex beam. This property provides us a possible approach for determining the TC of the vortex beam propagating through the atmospheric turbulence, which could have potential application in optical communication using optical vortices. PMID- 26366908 TI - Approximate analytical solution for waveguide excitation of a plane dielectric layer by a Gaussian beam at frustrated total internal reflection. AB - We present an approximate 2D asymptotic analytic theory of light field excitation in a plane thin dielectric layer under conditions of frustrated total internal reflection, when an inclined Gaussian beam, falling from a triangular prism, excites a decaying field in air spacing between a prism and a plane dielectric. Ignoring the radiation scattering on the sharp edges of a prism, we have obtained the formulas that allow us to compute spatial structures of an electromagnetic field in every point of space and to estimate the integral efficiency of waveguide mode excitation in a plane dielectric layer and the total energy of a reflected beam. It is shown that the width of an initial Gaussian beam has an effect on waveguide mode intensity. PMID- 26366909 TI - Linear astigmatism of confocal off-axis reflective imaging systems with N-conic mirrors and its elimination. AB - Linear astigmatism of plane-symmetric confocal off-axis reflective imaging systems with an arbitrary number of conic mirrors is derived. Linear astigmatism, a consequence of tilted astigmatic image planes, is the dominant aberration of this type of imaging system. In this work, the tilt angles of astigmatic image planes are obtained in closed form. An equation to eliminate the linear astigmatism is also derived. The presented theory is verified by examples. PMID- 26366910 TI - Optical methods for blood perfusion measurement--theoretical comparison among four different modalities. AB - Blood perfusion in human tissue can be measured in vivo by means of various optical methods, which seem to be very different from one another. The most prominent examples of them are laser Doppler flowmetry, laser speckle contrast imaging, diffuse correlation spectroscopy, and the most recently developed diffuse speckle contrast analysis. In this paper, we claim that these four seemingly different modalities are examining different aspects of the same entity the temporal autocorrelation function of scattered photons. We will show how the observables in each modality can be theoretically derived from the temporal autocorrelation function, and will discuss the merits and drawbacks of each modality in its practical use. PMID- 26366911 TI - Nondiffracting chirped Bessel waves in optical antiguides. AB - Chirped Bessel waves are introduced as stable (nondiffracting) solutions of the paraxial wave equation in optical antiguides with a power-law radial variation in their index of refraction. Through numerical simulations, we investigate the propagation of apodized (finite-energy) versions of such waves, with or without vorticity, in antiguides with practical parameters. The new waves exhibit a remarkable resistance against the defocusing effect of the unstable index potentials, outperforming standard Gaussians with the same full width at half maximum. The chirped profile persists even under conditions of eccentric launching or antiguide bending and is also capable of self-healing like standard diffraction-free beams in free space. PMID- 26366912 TI - Laguerre-Gaussian functions and generalized formulation of electromagnetic Gaussian Schell-model sources. AB - Fourier transform of the combination of Gaussian function and power functions of even exponents 2n(n=0,1,2,...) gives rise to a class of physically realizable electromagnetic sources with correlation properties expressible in terms of Laguerre-Gaussian functions. Relatively simple mathematical expressions of the electromagnetic beams produced by the Laguerre-Gaussian Schell-model sources are given for an investigation of the coherence and polarization properties and the higher-order coherence effect of the correlations between intensity fluctuations in the Laguerre-Gaussian Schell-model beams (Laguerre-GSMB) of any order n. Results obtained are compared numerically with the predictions of the classic electromagnetic Gaussian Schell-model beam that is the lowest-order Laguerre-GSM beams. PMID- 26366913 TI - Contrast enhancement for images in turbid water. AB - Absorption, scattering, and color distortion are three major degradation factors in underwater optical imaging. Light rays are absorbed while passing through water, and absorption rates depend on the wavelength of the light. Scattering is caused by large suspended particles, which are always observed in an underwater environment. Color distortion occurs because the attenuation ratio is inversely proportional to the wavelength of light when light passes through a unit length in water. Consequently, underwater images are dark, low contrast, and dominated by a bluish tone. In this paper, we propose a novel underwater imaging model that compensates for the attenuation discrepancy along the propagation path. In addition, we develop a robust color lines-based ambient light estimator and a locally adaptive filtering algorithm for enhancing underwater images in shallow oceans. Furthermore, we propose a spectral characteristic-based color correction algorithm to recover the distorted color. The enhanced images have a reasonable noise level after the illumination compensation in the dark regions, and demonstrate an improved global contrast by which the finest details and edges are enhanced significantly. PMID- 26366914 TI - Statistical properties of a partially coherent cylindrical vector beam in oceanic turbulence. AB - Propagation of a partially coherent cylindrical vector Laguerre-Gaussian (PCCVLG) beam passing through oceanic turbulence is studied with the help of the extended Huygens-Fresnel integral formula and unified theory of coherence and polarization of light. Analytical formula for the cross-spectral density matrix of a PCCVLG beam propagating in oceanic turbulence is derived, and the statistical properties, such as intensity distribution and degree of polarization, of a PCCVLG beam on propagation in oceanic turbulence are illustrated in detail. It is found that the statistical properties of a PCCVLG beam in oceanic turbulence vary as the sea-related parameters, initial coherence length, and mode orders vary, and such beam is depolarized on propagation. Our results will be useful in optical underwater communications, imaging, and sensing. PMID- 26366915 TI - Recovering Euclidean structure by conics and spheres: application to camera calibration. AB - A novel method of two-dimensional Euclidean structure recovery in one view from the projections of N parallel conics is proposed, which can be applied to camera calibration. Without considering the conic dual to the absolute points, we transform conic features from the homogeneous coordinates to the lifted coordinates. In the lifted space, the conic features have similar properties to the point or line features, which especially means that the homography can also be deduced by conic features directly. Our work gives a generic framework of recovering the Euclidean structure from conic features. A series of experiments with simulated and real data are conducted. The experiment results show that the proposed method has its validity in practical applications to camera calibration. PMID- 26366916 TI - Experimental demonstration of ghost imaging with an electromagnetic Gaussian Schell-model beam. AB - Recently, there has been a controversy about the dependence of the visibility of the ghost image on the degree of polarization (DOP) of a stochastic electromagnetic beam because of different definitions of the visibility. In this paper, we revisit ghost imaging with an electromagnetic Gaussian Schell-model (EGSM) beam. Through numerical examples based on the conventional definition of the visibility, we find that the visibility of the ghost image indeed increases or decreases with the increase of the DOP the beam source under certain conditions. We solve the controversy between literatures and the present paper through analyzing the r.m.s. widths of auto-correlation functions of the x component of the field and of the y component of the field. Furthermore, we carry out experimental demonstration of ghost imaging with an EGSM beam. Our experimental results verify the theoretical predictions. PMID- 26366917 TI - Visibility of sparkle in metallic paints. AB - For suitable illumination and observation conditions, sparkles may be observed in metallic coatings. The visibility of these sparkles depends critically on their intensity, and on the paint medium surrounding the metallic flakes. Based on previous perception studies from other disciplines, we derive equations for the threshold for sparkles to be visible. The resulting equations show how the visibility of sparkles varies with the luminosity and distance of the light source, the diameter of the metallic flakes, and the reflection properties of the paint medium. The predictions are confirmed by common observations on metallic sparkle. For example, under appropriate conditions even metallic flakes as small as 1 MUm diameter may be visible as sparkle, whereas under intense spot light the finer grades of metallic coatings do not show sparkle. We show that in direct sunlight, dark coarse metallic coatings show sparkles that are brighter than the brightest stars and planets in the night sky. Finally, we give equations to predict the number of visually distinguishable flake intensities, depending on local conditions. These equations are confirmed by previous results. Several practical examples for applying the equations derived in this article are provided. PMID- 26366918 TI - Zernike expansion of pupil filters: optimization of the signal concentration factor. AB - Amplitude pupil filters for optimizing the signal concentration factor for a point spread function of given transverse and/or axial widths are derived. The pupil is expanded in a basis of Zernike polynomials. It is shown that the pupil that maximizes the signal concentration factor for a given transverse gain has a quadratically varying amplitude profile, as was shown in a previous paper, while the pupil that maximizes the signal concentration factor for a given axial gain has a quartic amplitude profile. PMID- 26366920 TI - Omnidirectional absorption and off-resonance field enhancement in dielectric cylinders coated with graphene layers. AB - We investigate electromagnetic scattering and absorption by dielectric cylinders coated with a concentric plasmonic shell at arbitrary incidence angles. Exploiting bulk and surface plasmon resonances in the long wavelength regime, we obtain an analytical condition to achieve wide-angle enhanced absorption for both TE and TM polarizations. By using the Lorenz-Mie theory, we apply this result to investigate electromagnetic absorption in a silicon cylinder coated with a graphene monolayer epitaxially grown on silicon carbide. Our theoretical results show that enhanced absorption occurs for a broad frequency range in the terahertz, and that omnidirectional absorption exists at a frequency in between the bulk and localized surface plasmon resonances. By showing that omnidirectional absorption does not correspond to an extinction resonance, we associate this phenomenon with off-resonance field enhancement in this system, which in turn is explained in terms of Fano resonances in the graphene layer. PMID- 26366919 TI - Visual appearance measurement of surfaces containing pearl flakes. AB - The color, gloss, and texture (i.e., pearliness) of 15 glossy samples containing pearl flakes were investigated. Psychophysical experimental data from 21 observers were compared with measurement data. Color measurement data obtained using the CIE D/0 and ASTM E2539-08 multiangle geometry did not predict the overall color appearance variation of pearly samples. Pearly samples have a lower perceived glossiness than non-pearly surfaces with the same level of gloss treatment, but a much higher measured gloss. Pearliness describes the texture of pearly samples well and can be predicted as a function of the pearl flakes' average size and area coverage measured from magnified surface images. These results suggest that an image statistics approach is required to properly describe the visual appearance of pearly surfaces. PMID- 26366921 TI - Light propagation analysis using a translated plane angular spectrum method with the oblique plane wave incidence. AB - A novel angular spectrum method was proposed to numerically analyze off-axis free space light propagation on a translated plane to an arbitrary angle. Utilizing a shifted angular spectrum method based on an oblique incident plane wave assumption, a generalized light propagation formulation was obtained in a wide range of both tilt angles and sampling intervals, which overcame the limitations of prior attempts. A detailed comparison of the proposed angular spectrum method with prior methods is numerically presented for diffractive optics and computer generated holograms. The validity of the proposed method was confirmed experimentally by reconstructing a digital holographic image using a spatial light modulator. PMID- 26366922 TI - Ultrasound-modulated optical tomography: direct recovery of elasticity distribution from experimentally measured intensity autocorrelation. AB - Based on an ultrasound-modulated optical tomography experiment, a direct, quantitative recovery of Young's modulus (E) is achieved from the modulation depth (M) in the intensity autocorrelation. The number of detector locations is limited to two in orthogonal directions, reducing the complexity of the data gathering step whilst ensuring against an impoverishment of the measurement, by employing ultrasound frequency as a parameter to vary during data collection. The M and E are related via two partial differential equations. The first one connects M to the amplitude of vibration of the scattering centers in the focal volume and the other, this amplitude to E. A (composite) sensitivity matrix is arrived at mapping the variation of M with that of E and used in a (barely regularized) Gauss-Newton algorithm to iteratively recover E. The reconstruction results showing the variation of E are presented. PMID- 26366923 TI - Determining the phase and amplitude distortion of a wavefront using a plenoptic sensor. AB - We have designed a plenoptic sensor to retrieve phase and amplitude changes resulting from a laser beam's propagation through atmospheric turbulence. Compared with the commonly restricted domain of (-pi,pi) in phase reconstruction by interferometers, the reconstructed phase obtained by the plenoptic sensors can be continuous up to a multiple of 2pi. When compared with conventional Shack Hartmann sensors, ambiguities caused by interference or low intensity, such as branch points and branch cuts, are less likely to happen and can be adaptively avoided by our reconstruction algorithm. In the design of our plenoptic sensor, we modified the fundamental structure of a light field camera into a mini Keplerian telescope array by accurately cascading the back focal plane of its object lens with a microlens array's front focal plane and matching the numerical aperture of both components. Unlike light field cameras designed for incoherent imaging purposes, our plenoptic sensor operates on the complex amplitude of the incident beam and distributes it into a matrix of images that are simpler and less subject to interference than a global image of the beam. Then, with the proposed reconstruction algorithms, the plenoptic sensor is able to reconstruct the wavefront and a phase screen at an appropriate depth in the field that causes the equivalent distortion on the beam. The reconstructed results can be used to guide adaptive optics systems in directing beam propagation through atmospheric turbulence. In this paper, we will show the theoretical analysis and experimental results obtained with the plenoptic sensor and its reconstruction algorithms. PMID- 26366924 TI - Modal method for the 2D wave propagation in heterogeneous anisotropic media. AB - A multimodal method based on a generalization of the admittance matrix is used to analyze wave propagation in heterogeneous two-dimensional anisotropic media. The heterogeneity of the medium can be due to the presence of anisotropic inclusions with arbitrary shapes, to a succession of anisotropic media with complex interfaces between them, or both. Using a modal expansion of the wave field, the problem is reduced to a system of two sets of first-order differential equations for the modal components of the field, similar to the system obtained in the rigorous coupled wave analysis. The system is solved numerically, using the admittance matrix, which leads to a stable numerical method, the basic properties of which are discussed. The convergence of the method is discussed, considering arrays of anisotropic inclusions with complex shapes, which tend to show that Li's rules are not concerned within our approach. The method is validated by comparison with a subwavelength layered structure presenting an effective anisotropy at the wave scale. PMID- 26366925 TI - Deflectometry for measuring inhomogeneous refractive index fields in two dimensional gradient-index elements. AB - We present a numerical method for calculating inhomogeneous refractive index fields in rectangular gradient-index (GRIN) elements from measured boundary positions and slopes of a collection of rays that transit the medium. The inverse problem is reduced to a set of linear algebraic equations after approximating ray trajectories from the measured boundary values and is solved using a pseudo inverse algorithm for sparse linear equations. The ray trajectories are subsequently corrected using an iterative ray trace procedure to ensure consistency in the solution. We demonstrate our method in simulation by reconstructing a hypothetical rectangular GRIN element on a 15*15 discrete grid using 800 interrogating rays, in which RMS refractive index errors less than 0.5% of the index range (n(max)-n(min)) are achieved. Furthermore, we identify three primary sources of error and assess the importance of data redundancy and system conditioning in the reconstruction process. PMID- 26366926 TI - Hemispherical reflectance model for passive images in an outdoor environment. AB - We present a hemispherical reflectance model for simulating passive images in an outdoor environment where illumination is provided by natural sources such as the sun and the clouds. While the bidirectional reflectance distribution function (BRDF) accurately produces radiance from any objects after the illumination, using the BRDF in calculating radiance requires double integration. Replacing the BRDF by hemispherical reflectance under the natural sources transforms the double integration into a multiplication. This reduces both storage space and computation time. We present the formalism for the radiance of the scene using hemispherical reflectance instead of BRDF. This enables us to generate passive images in an outdoor environment taking advantage of the computational and storage efficiencies. We show some examples for illustration. PMID- 26366927 TI - Transformation of vector beams with radial and azimuthal polarizations in biaxial crystals. AB - We present both experimentally and theoretically the transformation of radially and azimuthally polarized vector beams when they propagate through a biaxial crystal and are transformed by the conical refraction phenomenon. We show that, at the focal plane, the transverse pattern is formed by a ring-like light structure with an azimuthal node, this node being found at diametrically opposite points of the ring for radial/azimuthal polarizations. We also prove that the state of polarization of the transformed beams is conical refraction-like, i.e., that every two diametrically opposite points of the light ring are linearly orthogonally polarized. PMID- 26366928 TI - Dietary L-Lysine Suppresses Autophagic Proteolysis and Stimulates Akt/mTOR Signaling in the Skeletal Muscle of Rats Fed a Low-Protein Diet. AB - Amino acids, especially L-leucine, regulate protein turnover in skeletal muscle and have attracted attention as a means of increasing muscle mass in people suffering from malnutrition, aging (sarcopenia), or a bedridden state. We previously showed that oral administration of L-lysine (Lys) by gavage suppressed proteolysis in skeletal muscles of fasted rats. However, the intake of Lys in the absence of other dietary components is unlikely in a non-experimental setting, and other dietary components may interfere with the suppressive effect of Lys on proteolysis. We supplemented Lys to a 10% casein diet and investigated the effect of Lys on proteolysis and autophagy, a major proteolytic system, in the skeletal muscle of rats. The rate of proteolysis was evaluated from 3-methylhisitidine (MeHis) released from isolated muscles, in plasma, and excreted in urine. Supplementing lysine with the 10% casein diet decreased the rate of proteolysis induced by intake of a low-protein diet. The upregulated autophagy activity [light chain 3 (LC3)-II/total LC3] caused by a low-protein diet was reduced, and the Akt/mTOR signaling pathway was activated by Lys. Importantly, continuous feeding of a Lys-rich 10% casein diet for 15 days increased the masses of the soleus and gastrocnemius muscles. Taken together, supplementation of Lys to a low protein diet suppresses autophagic proteolysis through the Akt/mTOR signaling pathway, and continuous feeding of a Lys-rich diet may increase skeletal muscle mass. PMID- 26366929 TI - Predicting isoproturon long-term mineralization from short-term experiment: Can this be a suitable approach? AB - A worldwide used pesticide - isoproturon (IPU) - was selected to test whether short-term experiments can be used to predict long-term mineralization of IPU in soil. IPU-mineralization was measured for 39 and 265 days in four different agricultural soils with a low mineralization dynamic. Additionally, in one soil IPU dissipation, formation and dissipation of metabolites, formation of non extractable residues (NER) and (14)C-microbial biomass from (14)C-IPU were monitored for 39 and 265 days. The data from short-term and long-term experiments were used for model fitting. The long-term dynamics of IPU mineralization were considerably overestimated by the short-term experiments in two soils with neutral pH, while in two other soils with low pH and lower mineralization, the long-term mineralization of IPU could be sufficiently predicted. Additional investigations in one of the soils with neutral pH showed that dissipation of IPU and metabolites could be correctly predicted by the short-term experiment. However, the formation of NER and (14)C-microbial biomass were remarkably overestimated by the short-term experiment. Further, it could be shown that the released NER and (14)C-microbial biomass were the main contributors of (14)CO2 formation at later incubation stages. Taken together, our results indicate that in soils with neutral pH short-term experiments were inadequate to predict the long-term mineralization of IPU. PMID- 26366930 TI - Hepatic Mucormycosis Mimicking Veno-occlusive Disease: Report of a Case and Review of the Literature. AB - The clinical history of a 12-year-old boy with trisomy 21 who suffered from relapsed pre-B cell acute lymphocytic leukemia with clinical symptoms of hepatic veno-occlusive disease and death is reported. The postmortem findings were significant for hepatic mucormycosis with selective involvement of the central veins, sinusoids, and portal tracts resulting in obstruction of the outflow tract and massive hepatocellular necrosis. Hematogenous dissemination of mucormycosis causing acute splenitis and hemorrhagic intestinal necrosis were also observed. To our knowledge, mucormycosis invasion of the central veins, sinusoids, and portal tracts by fungal hyphae resulting in a syndrome mimicking hepatic veno occlusive disease has not been previously reported. PMID- 26366931 TI - Short Communication: SCD14 and SCD163 Levels Are Correlated with VACS Index Scores: Initial Data from the Blunted Immune Recovery in CORE Patients with HIV (BIRCH) Cohort. AB - The relationship between markers of monocyte/macrophage activation (sCD14 and sCD163) and components of the Veterans Aging Cohort Study (VACS) score, which predict mortality in patients with HIV, in immunologic nonresponders (INRs) is not defined. HIV(+) subjects with >12 months of continuous virologic suppression and persistent CD4 <250 cells/mm(3) were enrolled at the CORE Center, Chicago. Subjects had a single visit where history was taken and blood drawn. ELISA assays for sCD14 and sC163 were performed at Blood Systems, CA. Descriptive statistics were performed using SAS. We enrolled 43 subjects with persistent CD4 <250 after a median of 32 months of continuous viral suppression. We found elevated markers of monocyte/macrophage activation; sCD14 and sCD163 correlated with higher VACS scores as well as hepatitis C virus (HCV) coinfection and FIB-4 score, components of the VACS index. In this cohort of immunologic nonresponders, there was a significant correlation between markers of monocyte/macrophage activation and the VACS score. Among components of the VACS index, we did not find a significant association between HCV coinfection and sCD14; however, there was a significant association between HCV coinfection and sCD163. PMID- 26366932 TI - Random phylogenies and the distribution of branching times. AB - Phylogenetic trees reconstructed without fossils have become an important source of information to study evolutionary processes. A widely used method to describe patterns of phylogenetic diversification is known as the lineages-through-time (LTT) plot. Recently, it has been shown that it is possible to predict the distribution of the branching times of a phylogeny, thus making possible to derive a theoretical LTT curve conditioned on diversification parameters. Here, I review some aspects related to this prediction showing how to derive it for any time-dependent model of diversification, as well as calculating a prediction interval around a theoretical LTT curve. The accuracy of the prediction interval was assessed with simulations using fixed or random tree sizes under constant rate models as well as two models of time-dependent diversification. The prediction intervals were relatively narrower and more accurate for larger trees. The features of this approach are discussed as well as its potential applications. PMID- 26366933 TI - The Luria-Delbruck protocol is still the most practical. AB - It is theoretically appealing to determine microbial mutation rates by counting mutant cells in two successive generations. However, major experimental difficulties have been largely ignored, causing unreliable estimates of mutation rates to be unwittingly accepted. Counting mutant cells twice in the same liquid culture incurs appreciable errors that are difficult to quantify; maintaining synchronous cell growth for 25 or more generations is an equally daunting laboratory feat. PMID- 26366934 TI - Batch and fixed-bed column studies for biosorption of Zn(II) ions onto pongamia oil cake (Pongamia pinnata) from biodiesel oil extraction. AB - The present work, analyzes the potential of defatted pongamia oil cake (DPOC) for the biosorption of Zn(II) ions from aqueous solutions in the both batch and column mode. Batch experiments were conducted to evaluate the optimal pH, effect of adsorbent dosage, initial Zn(II) ions concentration and contact time. The biosorption equilibrium and kinetics data for Zn(II) ions onto the DPOC were studied in detail, using several models, among all it was found to be that, Freundlich and the second-order model explained the equilibrium data well. The calculated thermodynamic parameters had shown that the biosorption of Zn(II) ions was exothermic and spontaneous in nature. Batch desorption studies showed that the maximum Zn(II) recovery occurred, using 0.1 M EDTA. The Bed Depth Service Time (BDST) and the Thomas model was successfully employed to evaluate the model parameters in the column mode. The results indicated that the DPOC can be applied as an effective and eco-friendly biosorbent for the removal of Zn(II) ions in polluted wastewater. PMID- 26366935 TI - The relationship between hypertension and plasma allantoin, uric acid, xanthine oxidase activity and nitrite, and their predictive capacity in severe preeclampsia. AB - It is controversial that uric acid (UA) levels are related to the severity of hypertension in preeclampsia (PE). Our aim in this study was to determine whether UA, xanthine oxidase activity (XOA), allantoin and nitrite levels are related to arterial blood pressure (BP) in PE. We formed a control group (n = 20) and a PE group (n = 20) for the study. Their BPs and plasma UA, XOA, allantoin and nitrite levels were measured. The values from the control and PE pregnant women were assessed via a Wilcoxon matched-pairs test. A Pearson correlation test was also performed. In addition, the diagnostic value of these tests was evaluated via receiver operating characteristic (ROC) analysis. The BP, UA, XOA and allantoin levels in the PE patients were found to be higher when compared with those of the pregnant controls. The UA, XOA and allantoin levels showed high correlations with BP in cases of PE. However, there was no superiority among the correlations. No differences were observed between the groups in terms of nitrite levels and the relationship between nitrite and BP. UA, XOA and allantoin levels may be high due to placental cell death because of abnormal trophoblastic activity observed in PE. Moreover, the reactive oxygen products that are created during the genetic material degradation may explain how UA, XOA and allantoin levels are related to BP. According to ROC analysis, UA, XOA and allantoin assays are reliable predictors for the determination of PE. PMID- 26366936 TI - Prevalence of Pulmonary Hypertension and its Influence on Survival in Patients With Advanced Chronic Obstructive Pulmonary Disease Prior to Lung Transplantation. AB - INTRODUCTION: Prevalence of pulmonary hypertension (PH) and its influence on survival in chronic obstructive pulmonary disease (COPD) are not well studied in the lung allocation score (LAS) era. METHODS: The UNOS database was queried from 2005 to 2013 to identify first-time adult lung transplant candidates with COPD who were tracked from wait list entry date until death or censoring to determine both prevalence and influence of PH. Using right heart catheterization measurements, mild PH was defined as mean pulmonary artery pressure (mPAP) >= 25 mmHg and severe >= 35 mmHg. RESULTS: Of 1315 COPD candidates not transplanted, 1243 were used for survival analysis using Cox proportional hazards models, and 1010 (mild PH) and 244 (severe PH) were used for propensity score matching, respectively. A total of 52% (652) of subjects had PH mPAP >= 25 mmHg. Univariate analysis revealed significant differences in survival for mild PH (HR = 1.769; 95% CI: 1.331, 2.351; p < 0.001) and severe PH (HR = 3.271; 95% CI: 2.311, 4.630; p < 0.001). Kaplan-Meier survival function demonstrated significant disparities for mild PH (Log-rank test: Chi-square1: 15.87, p < 0.0001) and severe PH (Log rank test: Chi-square1: 50.13, p < 0.0001). Multivariate Cox models identified significant risk for death for mild PH (HR = 1.987; 95% CI: 1.484, 2.662; p < 0.001) and severe PH (HR = 3.432; 95% CI: 2.410, 4.888; p < 0.001). Propensity score matching confirmed increased mortality hazard associated with mild PH (HR = 2.280; 95% CI: 1.425, 3.649; p = 0.001) and severe PH (HR = 7.000; 95% CI: 2.455, 19.957; p < 0.001). CONCLUSIONS: PH is highly prevalent in advanced COPD and associated with a significantly higher risk for mortality. PMID- 26366937 TI - Rolapitant for the treatment of chemotherapy-induced nausea and vomiting. AB - Chemotherapy-induced nausea and vomiting is a significant clinical issue which affects patient's quality of life and treatment decisions. Significant improvements in the control of chemotherapy-induced nausea and vomiting have occurred in the past 15 years with the introduction of new antiemetic agents 5 HT3, receptor antagonists, neurokinin-1 (NK-1) receptor antagonists, and olanzapine. Aprepitant was the first NK-1 receptor antagonist introduced (2003) for the prevention of chemotherapy-induced nausea and vomiting in combination with a 5-HT3 receptor antagonist and dexamethasone. A second NK-1 receptor antagonist netupitant was approved for use in October 2014. Phase III clinical trials of an additional NK-1 receptor antagonist rolapitant have been completed, and the data have been submitted for regulatory approval. A description of rolapitant and its role in chemotherapy-induced nausea and vomiting will be presented, along with a comparison of the other neurolinin-1 receptor antagonists aprepitant and netupitant. PMID- 26366938 TI - Clinical pharmacology of antifungal agents in pediatrics: children are not small adults. AB - The optimal dosage information to improve the prognosis of invasive fungal infections in children and neonates is still limited and current dosing strategies are supported mainly by adult studies and extrapolation. Significant progress has been made to address this need in the last decade. Pre-clinical models and pharmacokinetic-pharmacodynamic (PK-PD) bridging studies supported by pediatric pharmacokinetic studies have investigated optimal dosing regimens for neonates and children. Here, we review the rationale for various antifungal regimens in infants and children. PMID- 26366939 TI - Characterization of TPN729 metabolites in humans using ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry. AB - TPN729 has been reported as a novel phosphodiesterase type 5 (PDE5) inhibitor to treat erectile dysfunction, and is currently being tested in clinical trials. In addition to the potent inhibition against PDE5, TPN729 is regarded as a better alternative to provide fewer side effects and better patient compliance. Given the potential therapeutic benefits of TPN729, it is of great importance to elucidate its metabolic characteristics in drug development. This study is the first to investigate the metabolic fate of TPN729 in humans. A rapid and reliable analytical method based on ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS) was established to investigate the metabolic profiles of TPN729 in human plasma, urine, and feces after its oral administration. As a result, a total of 22 metabolites were identified, of which seven were confirmed in comparison with the reference substances. The incubations of the metabolite references in human hepatocytes and aldehyde trapping experiment were further conducted to investigate its metabolic pathways. The results of the present study indicated the extensive metabolism of TPN729 in humans, including oxidative deamination, oxidative ring opening, N-dealkylation, N-oxidation, hydroxylation, dehydrogenation, lactam formation, and glucuronidation. M3 resulting from N-dealkylation was the major circulating substance detected in human plasma. The principal metabolites detected in human feces were products of oxidative deamination and oxidative ring opening. The parent drug was identified as the major component in urine. Taken together, this study provided valuable information on the metabolic fate of TPN729 in humans, and applicable analytical strategies for rapid metabolic elucidation in complex matrix samples through the useful and reliable UPLC/Q-TOF MS technique. PMID- 26366940 TI - Impact of noise on self-rated job satisfaction and health in open-plan offices: a structural equation modelling approach. AB - This study uses a structural equation model to examine the effects of noise on self-rated job satisfaction and health in open-plan offices. A total of 334 employees from six open-plan offices in China and Korea completed a questionnaire survey. The questionnaire included questions assessing noise disturbances and speech privacy, as well as job satisfaction and health. The results indicated that noise disturbance affected self-rated health. Contrary to popular expectation, the relationship between noise disturbance and job satisfaction was not significant. Rather, job satisfaction and satisfaction with the environment were negatively correlated with lack of speech privacy. Speech privacy was found to be affected by noise sensitivity, and longer noise exposure led to decreased job satisfaction. There was also evidence that speech privacy was a stronger predictor of satisfaction with environment and job satisfaction for participants with high noise sensitivity. In addition, fit models for employees from China and Korea showed slight differences. PRACTITIONER SUMMARY: This study is motivated by strong evidence that noise is the key source of complaints in open-plan offices. Survey results indicate that self-rated job satisfaction of workers in open-plan offices was negatively affected by lack of speech privacy and duration of disturbing noise. PMID- 26366942 TI - Walking alongside: a qualitative study of the experiences and perceptions of academic nurse mentors supporting early career nurse academics. AB - PURPOSE: This study explores the experiences and perceptions of academic nurse mentors supporting early career nurse academics (ECNAs). METHODS: Interviews were undertaken with mentors following a mentoring partnership with ECNAs. Data were transcribed verbatim and analysed using a process of thematic analysis. FINDINGS: Four themes emerged from the data, namely; motivation for mentoring; constructing the relationship; establishing safe boundaries and managing expectations. CONCLUSIONS: This study provides a unique insight into the experiences of mentoring within the context of an academic leadership programme for nurses. Such insights highlight the issues facing academics from professional disciplines and can inform strategies to support their career development. CLINICAL RELEVANCE: A sustainable academic nursing workforce is crucial to ensure that effective preparation of future generations of expert clinical nurses. Therefore, it is important to consider strategies that could strengthen the academic nursing workforce. PMID- 26366941 TI - Case-ascertained study of household transmission of seasonal influenza - South Africa, 2013. AB - OBJECTIVES: The household is important in influenza transmission due to intensity of contact. Previous studies reported secondary attack rates (SAR) of 4-10% for laboratory-confirmed influenza in the household. Few have been conducted in middle-income countries. METHODS: We performed a case-ascertained household transmission study during May-October 2013. Index cases were patients with influenza-like-illness (cough and self-reported or measured fever (>=38 degrees C)) with onset in the last 3 days and no sick household contacts, at clinics in South Africa. Household contacts of index cases with laboratory-confirmed influenza were followed for 12 days. RESULTS: Thirty index cases in 30 households and 107/110 (97%) eligible household contacts were enrolled. Assuming those not enrolled were influenza negative, 21/110 household contacts had laboratory confirmed influenza (SAR 19%); the mean serial interval was 2.1 days (SD = 0.35, range 2-3 days). Most (62/82; 76%) household contacts who completed the risk factor questionnaire never avoided contact and 43/82 (52%) continued to share a bed with the index case after illness onset. CONCLUSION: SAR for laboratory confirmed influenza in South Africa was higher than previously reported SARs. Household contacts did not report changing behaviors to prevent transmission. These results can be used to understand and predict influenza transmission in similar middle-income settings. PMID- 26366943 TI - Yohimbine is a 5-HT1A agonist in rats in doses exceeding 1 mg/kg. AB - Yohimbine is a prototypical alpha2-adrenergic receptor antagonist. Due to its relatively high selectivity, yohimbine is often used in experiments whose purpose is to examine the role of these receptors. For example, yohimbine has been employed at doses of 1-5 mg/kg to reinstate drug-seeking behavior after extinction or to antagonize general anesthesia, an effects presumably being a consequence of blocking alpha2-adrenergic receptors. In this report we characterized dose-dependent autonomic and behavioral effects of yohimbine and its interaction with an antagonist of 5-HT1A receptors, WAY 100,635. In low doses (0.5-2 mg/kg i.p.) yohimbine induced locomotor activation which was accompanied by a tachycardia and mild hypertension. Increasing the dose to 3-4.5 mg/kg reversed the hypertension and locomotor activation and induced profound hypothermia. The hypothermia as well as the suppression of the locomotion and the hypertension could be reversed by the blockade of 5-HT1A receptors with WAY 100635. Our data confirm that yohimbine possesses 5-HT1A properties, and demonstrated that in doses above 1mg/kg significantly activate these receptors. PMID- 26366944 TI - Melatonin attenuates methamphetamine-induced inhibition of neurogenesis in the adult mouse hippocampus: An in vivo study. AB - Methamphetamine (METH), a highly addictive psychostimulant drug, is known to exert neurotoxic effects to the dopaminergic neural system. Long-term METH administration impairs brain functions such as cognition, learning and memory. Newly born neurons in the dentate gyrus of the hippocampus play an important role in spatial learning and memory. Previous in vitro studies have shown that METH inhibits cell proliferation and neurogenesis in the hippocampus. On the other hand, melatonin, a major indole secreted by the pineal gland, enhances neurogenesis in both the subventricular zone and dentate gyrus. In this study, adult C57BL/6 mice were used to study the beneficial effects of melatonin on METH induced alterations in neurogenesis and post-synaptic proteins related to learning and memory functions in the hippocampus. The results showed that METH caused a decrease in neuronal phenotypes as determined by the expressions of nestin, doublecortin (DCX) and beta-III tubulin while causing an increase in glial fibrillary acidic protein (GFAP) expression. Moreover, METH inhibited mitogen-activated protein kinase (MAPK) signaling activity and altered expression of the N-methyl-d-aspartate (NMDA) receptor subunits NR2A and NR2B as well as calcium/calmodulin-dependent protein kinase II (CaMKII). These effects could be attenuated by melatonin pretreatment. In conclusion, melatonin prevented the METH induced reduction in neurogenesis, increase in astrogliogenesis and alteration of NMDA receptor subunit expression. These findings may indicate the beneficial effects of melatonin on the impairment of learning and memory caused by METH. PMID- 26366947 TI - Perioperative MI: Data, practice, and questions. PMID- 26366945 TI - Base resolution methylome profiling: considerations in platform selection, data preprocessing and analysis. AB - Bisulfite treatment-based methylation microarray (mainly Illumina 450K Infinium array) and next-generation sequencing (reduced representation bisulfite sequencing, Agilent SureSelect Human Methyl-Seq, NimbleGen SeqCap Epi CpGiant or whole-genome bisulfite sequencing) are commonly used for base resolution DNA methylome research. Although multiple tools and methods have been developed and used for the data preprocessing and analysis, confusions remains for these platforms including how and whether the 450k array should be normalized; which platform should be used to better fit researchers' needs; and which statistical models would be more appropriate for differential methylation analysis. This review presents the commonly used platforms and compares the pros and cons of each in methylome profiling. We then discuss approaches to study design, data normalization, bias correction and model selection for differentially methylated individual CpGs and regions. PMID- 26366946 TI - Soy isoflavone metabolism in cats compared with other species: urinary metabolite concentrations and glucuronidation by liver microsomes. AB - 1. Soybean is a common source of protein in many pet foods. Slow glucuronidation of soy-derived isoflavones in cats has been hypothesized to result in accumulation with adverse health consequences. Here, we evaluated species' differences in soy isoflavone glucuronidation using urine samples from cats and dogs fed a soy-based diet and liver microsomes from cats compared with microsomes from 12 other species. 2. Significant concentrations of conjugated (but not unconjugated) genistein, daidzein and glycitein, and the gut microbiome metabolites, dihydrogenistein and dihydrodaidzein, were found in cat and dog urine samples. Substantial amounts of conjugated equol were also found in cat urine but not in dog urine. 3. beta-Glucuronidase treatment showed that all these compounds were significantly glucuronidated in dog urine while only daidzein (11%) and glycitein (37%) showed any glucuronidation in cat urine suggesting that alternate metabolic pathways including sulfation predominate in cats. 4. Glucuronidation rates of genistein, daidzein and equol by cat livers were consistently ranked within the lowest 3 out of 13 species' livers evaluated. Ferret and mongoose livers were also ranked in the lowest four species. 5. Our results demonstrate that glucuronidation is a minor pathway for soy isoflavone metabolism in cats compared with most other species. PMID- 26366948 TI - To the Editor: Sleep apnea ABCs. PMID- 26366949 TI - In Reply: Sleep apnea ABCs. PMID- 26366950 TI - To the Editor: EMR notes should communicate and educate. PMID- 26366951 TI - 2015 Update on Parkinson disease. AB - Parkinson disease is still diagnosed by clinical signs, and its most effective treatment is still levodopa. However, an improved understanding of the disease is leading to new diagnostic tools and treatments. PMID- 26366952 TI - What is the difference between palliative care and hospice care? PMID- 26366953 TI - Occult satellite metastasis of an auricular melanoma. PMID- 26366954 TI - Herpes zoster triplex. PMID- 26366955 TI - Middle East respiratory syndrome: SARS redux? AB - Middle East respiratory syndrome (MERS) is caused by the Middle East respiratory syndrome coronavirus (MERS-CoV). Although predominantly affecting countries across the Arabian Peninsula, the infection has been exported by travelers to countries around the world, including the United States. The virus has caused several healthcare-related outbreaks, so prompt recognition and patient isolation are critical to containing the spread of infection. Healthcare providers are urged to stay current on the evolving outbreak, and to screen at-risk travelers for possible MERS. PMID- 26366956 TI - Troponin elevation after noncardiac surgery: Significance and management. AB - How to interpret and manage troponin elevations after noncardiac surgery is a common clinical question for cardiologists and internists. An estimated 5% to 25% of patients who undergo noncardiac surgery have an elevated postoperative troponin level. Patients with troponin elevation are at higher short-term and long-term risk of morbidity and mortality. Current guidelines provide few recommendations on how to manage these patients. The authors review the evidence and guidelines and propose treatment strategies. PMID- 26366957 TI - Postoperative troponin surveillance: A diagnostic dilemma. PMID- 26366958 TI - Ankle pain in a young woman with Gaucher disease. PMID- 26366959 TI - Lactic acidosis: Clinical implications and management strategies. AB - In hospitalized patients, elevated serum lactate levels are both a marker of risk and a target of therapy. The authors describe the mechanisms underlying lactate elevations, note the risks associated with lactic acidosis, and outline a strategy for its treatment. PMID- 26366960 TI - Complete mitochondrial genome of Garrulax elliotii (Passeriformes, Timaliidae). AB - Garrulax elliotii belonged to Passeriformes, one of the members of Timaliidae family. It was a kind of unique and resident species habitat in the evergreen broadleaf forest and alpine shrub belt. The complete mitochondrial genome of G. elliotii was constituted by 13 protein-coding genes (PCGs), 22 transfer ribonucleic acid (tRNA) genes, two Ribosomal RNA (12SrRNA and 16SrRNA) genes, and two control regions (D-loop) genes. ND6 and eight tRNA genes (tRNA(Gln), tRNA(Ala), tRNA(Asn), tRNA(Cys), tRNA(Tyr), tRNA(Ser(UCN)), tRNA(Pro), and tRNA(Glu)) encoded on light strand, and the other 12 protein-coding genes encoded on heavy strand. Mitochondrial genes had been widely used in studies of phylogenetic relationships, molecular diagnostics, and an important tool for genome architecture, it has a significance mean for us provided the complete mitochondrial genome of G. elliotii to the Timaliidae family construction in the future. PMID- 26366961 TI - Mood Stabilizers in Children and Adolescents With Autism Spectrum Disorders. AB - Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders including autistic disorder, Asperger syndrome, and pervasive developmental disorder not otherwise specified as to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. All these categories are grouped together in Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, classification under the category of Autism Spectrum Disorders.Behavioral disorders including irritability, attention-deficit/hyperactivity disorder (ADHD) symptoms, and aggression are additional symptoms found in up to 20% of children and adolescents with ASD and require careful evaluation for appropriate treatment. Attention-deficit/hyperactivity disorder is defined by impaired attention, hyperactivity, and impulsivity, whereas ASD is defined by social dysfunction, communicative impairment, and restricted/repetitive behaviors. They should be distinctly evaluated in children and adolescents with ASD and intellectual disability in contrast to individuals without intellectual disability, because significant differences between these conditions exist. Mood disorders are also common in ASD and should be systematically investigated in this population of children and adolescents. Approximately 50% of children and adolescents with ASD receive medication for comorbid behavioral/ADHD and mood symptoms, mostly stimulants, antiepileptics and antipsychotics. Guidelines for the evaluation and treatment including medications for ADHD-like symptoms have recently been provided and should be carefully considered. Antiepileptic drugs are commonly used in ASDs with epilepsy, because seizures are associated with ASD in 10% to 30% of young patients, and as mood stabilizers. Lithium is another option for children and adolescents with ASD who present with symptoms of a mood disorder, such as elevated moods/euphoria, mania, and paranoia, whether accompanied or not by irritability. Experimental treatments are under investigation and currently include arbaclofen, a gamma-aminobutyric acid agent, and N-acetylcisteine, a glutamate agent. PMID- 26366962 TI - Lacosamide Induced Psychosis: Case Report, Review of Differential Diagnosis and Relevant Pharmacokinetics. AB - Lacosamide (LCM) is an antiepileptic medication used as an adjunctive treatment for partial seizures. Psychosis associated with LCM use is a rarely documented phenomenon, which may be difficult to detect in the context of the often complicated clinical presentation of epilepsy. We report the development of psychosis in a young woman after the use of LCM, which subsequently resolved with its discontinuation. The possible differential diagnosis and pharmacokinetic nuances are discussed. This is the first case report of LCM-induced psychosis in the United States. PMID- 26366963 TI - Mucuna pruriens in Parkinson Disease: A Kinetic-Dynamic Comparison With Levodopa Standard Formulations. AB - OBJECTIVES: We compared levodopa (LD) kinetic-dynamic profile of a dose of LD/aromatic amino acid decarboxylase peripheral inhibitors versus a nominally equivalent dose of a commercial Mucuna pruriens (Mucuna) seeds extract in 2 patients with Parkinson disease chronically taking LD standard combined with self prescribed Mucuna. METHODS: Patients were challenged with a fasting morning dose of 100 mg LD/25 mg carbidopa (patient 1) or benserazide (patient 2) versus 100 mg LD from Mucuna capsules in 2 different sessions, after a 12-hour standard LD formulations' washout. They underwent kinetic-dynamic LD monitoring based on LD dose intake and simultaneous serial assessments of plasma drug concentrations and motor test performances. Quantitative analysis of LD in Mucuna capsules was also performed. RESULTS: Levodopa bioavailability was markedly lower after Mucuna administration compared with LD standard formulations: in patient 1, peak plasma LD concentration (Cmax) decreased from 2.0 to 1.0 mg/L and the area under the plasma concentration time curve from 137 to 33.6 mg/L per minute; in patient 2, Cmax was 0.7 mg/L after LD/benserazide and nearly undetectable after Mucuna. In patient 1, impaired LD bioavailability from Mucuna resulted in reduced duration and overall extent of drug response compared with LD/carbidopa. In patient 2, no significant subacute LD motor response was observed in either condition. Quantitative analysis of Mucuna formulation confirmed the 100 mg LD content for the utilized capsules. CONCLUSIONS: Our results show an impaired LD bioavailability from Mucuna preparation, as expected by the lacking aromatic amino acid decarboxylase inhibitors coadministration, which might explain the suggested lower dyskinetic potential of Mucuna compared with standard LD formulations. PMID- 26366964 TI - Serotonin Syndrome Induced by Fentanyl in a Child: Case Report. AB - Serotonin syndrome (SS) is a potentially fatal condition associated with increased serotonergic activity in the central nervous system that can be attributed to certain drugs or interactions between drugs. There are some published articles reporting this syndrome caused by the combination of fentanyl and selective serotonin reuptake inhibitors antidepressants in adult patients; however, there are no reports of SS associated to the use of fentanyl as a single causative agent. The author reports a case of a 7-year-old boy who was admitted to the emergency department with neurological deterioration secondary to an intracerebral hemorrhage. The patient was operated to remove the bleeding. Postoperatively, he experienced a diversity of progressive neurological signs (shivering, tremor, hypertonia, hyperreflexia, clonus, bilateral mydriasis, and intracranial hypertension), which were initially considered to be signs of neurological deterioration, but finally, it was proved that they were part of a SS caused by fentanyl.The absence of concomitant use of another medications known to induce SS and the dramatic improving observed after stopping fentanyl strongly indicates that fentanyl was the causative agent in this case of SS.Fentanyl is a medication used frequently, and therefore, clinicians should be aware of this potential adverse effect when this drug is administered. PMID- 26366965 TI - Unique Scopolamine Withdrawal Syndrome After Standard Transdermal Use. AB - We report the case of a 62-year-old woman who developed a withdrawal syndrome after using a standard 1.5-mg transdermal scopolamine (TDS) patch behind the ear to prevent motion sickness during sailing. The patient, who had used TDS occasionally for years without significant adverse effects, more recently, having worn a patch continuously for 7 days, approximately 24 to 36 hours after removing the patch developed dizziness, nausea, sweating, fatigue, and drowsiness. All symptoms disappeared without therapy in about 2 days. Approximately 1 year after the first episode, though, a very similar, more severe disabling reaction developed on 2 occasions. Drowsiness and malaise were accompanied by severe asthenia, orthostatic sweating, inability to stand, and hypotension. All clinical tests (electrocardiogram; spirometry; blood cell count; plasma levels of cortisol, sodium, and potassium; and liver and kidney function tests) were negative, and symptoms disappeared slowly, after several days. Although we are certain that scopolamine was responsible for the symptoms, we are less clear as to the nature of the disorder. The effects being more severe after a more prolonged use of the TDS patch, the increase in severity each successive time, and the time lag between removing the patch and appearance of symptoms all indicated a withdrawal syndrome for which several mechanisms may be suggested. PMID- 26366966 TI - A Comparison of Botox 100 U/mL and Dysport 100 U/mL Using Dose Conversion Ratio 1: 3 and 1: 1.7 in the Treatment of Cervical Dystonia: A Double-Blind, Randomized, Crossover Trial. AB - OBJECTIVES: Intramuscular injections of botulinum toxin (BTX) are used as symptomatic treatment for cervical dystonia. Botox and Dysport are commercial products containing BTX; however, dosage and concentration of the prepared solution vary considerably among studies. The concentration of BTX in the prepared solution affects clinical outcome. This double-blind, randomized crossover trial compares Botox and Dysport in 2 different dose conversion ratios (1:3 and 1:1.7) when diluted to the same concentration (100 U/mL). METHODS: Forty six patients with cervical dystonia received 3 different treatments, Botox in 2 different doses and Dysport as control treatment. The efficacy was evaluated 4 and 12 weeks after treatment using 5 instruments, including Toronto Western Spasmodic Torticollis Rating Scale. RESULTS AND CONCLUSION: The primary outcome was the estimated median Toronto Western Spasmodic Torticollis Rating Scale total score, which was 1.96 points higher for Botox (1:3) compared with Dysport at week 4, but the difference was not statistically significant (confidence interval, 0.88-4.61; P = 0.0799). No significant differences were seen between Botox (1:1.7) and Dysport. At week 12, a statistically significant difference in effect between Botox (1:3) and Dysport was observed, suggesting a shorter duration of effect for Botox when this ratio (low dose) was used. Furthermore, the patients' assessments showed that the ratio 1:3 resulted in suboptimal efficacy of Botox. These secondary outcome observations indicate that the dose conversion ratio between Dysport 100 U/mL and Botox 100 U/mL may be lower than 1:3, but this must be further validated in a larger patient material. PMID- 26366967 TI - Paliperidone Palmitate Depot in the Long-term Treatment of Psychotic Bipolar Disorder: A Case Series. AB - OBJECTIVES: The treatment of bipolar disorder (BD) cannot be limited to the remission of acute phases but includes the long-term treatment in order to prevent relapses, poor outcome, and chronicity. The purpose of this article is to present 3 cases of severe psychotic bipolar patients treated with monthly injection of paliperidone pamoate. METHODS: Three poor-compliant severe psychotic BD patients were initiated to paliperidone palmitate (100-150 mg monthly), and they were followed up for 12 months. Young Mania Rating Scale and Hamilton Depression Rating Scale were administered at baseline and during monthly follow up visits. RESULTS: None of patients presented recurrences or relapses during the 12-month follow-up period. The patients did not develop adverse effects or significant changes in metabolism. CONCLUSIONS: These preliminary results indicate that paliperidone palmitate (100-150 mg monthly) may be a therapeutic option for long-term treatment of psychotic BD, particularly for poor-compliant severe patients. These results have to be confirmed in double-blind studies with bipolar patients not necessarily belonging to psychotic subtype. PMID- 26366968 TI - Augmentation Therapy With Serial Intravenous Ketamine Over 18 Months in a Patient With Treatment Resistant Depression. AB - Major depressive disorder is a severe illness that affects 3% to 7% of adults annually in the United States. About 30% of these individuals are refractory to multiple treatment trials. Recent reports have found a significant and almost immediate improvement in depressive symptoms after single or multiple ketamine intravenous infusions (IVIs) in such patients. We present the case of A.B., a patient with treatment-resistant depression (TRD) including to subgenual deep brain stimulation, who went into remission after augmentation with 6 ketamine IVIs (0.5 mg/kg) over a 3-week period. However, she had a reemergence of depressive symptoms 4 months later and received a second series of 3 ketamine IVIs over the course of a week. A.B. again went into remission and maintained this for the next 8 months. At this time, she experienced a reemergence of depressive symptoms and was treated with the third series of ketamine IVIs (3 infusions over the course of a week). Because A.B. has now been in remission for 6 months. A.B. has received a total of 12 ketamine IVIs over the course of 18 months. No significant adverse events have occurred. To our knowledge, this is the first case of long-term ketamine efficacy as augmentation therapy in TRD over the course of 18 months. There is a need for studies examining the long-term management of TRD with IV ketamine. Guidelines for maintenance ketamine IVIs in TRD also need to be developed. PMID- 26366969 TI - Pisa-Like Syndrome Under Baclofen in a Patient With Spastic Hemiparesis due to Ischemic Stroke. AB - In its original description, Pisa syndrome was reported as an iatrogenic dystonia of the trunk caused by neuroleptic drugs. However, sometimes, not dystonic lateral flexion of the trunk is described as Pisa syndrome. These observations support the possibility of a drug-induced lateral flexion of the trunk with clinical presentation similar to Pisa syndrome, although with a different etiology and pathophysiology. Here, we describe the case of a male patient, with a previous ischemic stroke and residual spastic hemiparesis to the right side, who subacutely developed a dramatic lateral flexion of trunk (approximately 45 degrees to the right) a few days after the introduction of Baclofen (5 mg 3 times per day). After the discontinuation of baclofen, a full recovery of the correct posture was obtained. In this respect, our case is paradigmatic: it is drug-induced but not clearly dystonic in its manifestation. Baclofen reduces the spasticity depressing the monosinaptic and polisinaptic reflex in the spinal cord by stimulating Gamma-aminobutyric acid B (GABA-B) receptors, which inhibit the release of excitatory amino acids, glutamate and aspartate. We believe that the definition of Pisa syndrome for these forms, not clearly dystonic, might be not completely appropriate, but they should be defined more correctly as Pisa-like syndromes. PMID- 26366970 TI - Are Second-Generation Antipsychotics Useful in Tardive Dystonia? AB - OBJECTIVE: To review the current evidence on the effectiveness of second generation antipsychotics (SGAs) in the treatment of tardive dystonia (TDt) and give recommendations for treatment. METHODS: Medline/PubMed/Psyclit/Embase database searches were conducted in January 2015, and a manual review of references within the retrieved articles was done. All articles in English and those that had English abstracts and dealt with treatment of TDt were included. RESULTS: Our search and review yielded a total of 88 reports (none of them a controlled trial) involving 145 patients treated with one of the 5 SGAs. Clozapine has the maximum number of published reports (52 reports involving 90 subjects, whereas there were 36 reports involving 55 subjects treated with other SGAs, including olanzapine, risperidone, quetiapine, aripiprazole, and perospirone). CONCLUSIONS: The available evidence points to the effectiveness of clozapine as monotherapy and in combination with clonazepam for the treatment of TDt. When clozapine is not an option, olanzapine and quetiapine are reasonable alternatives. Given the lack of controlled trials, future focus should be on conducting randomized, placebo-controlled, multicenter, collaborative controlled clinical trials of several years' duration. PMID- 26366971 TI - Caffeine and Progression of Parkinson Disease: A Deleterious Interaction With Creatine. AB - OBJECTIVE: Increased caffeine intake is associated with a lower risk of Parkinson disease (PD) and is neuroprotective in mouse models of PD. However, in a previous study, an exploratory analysis suggested that, in patients taking creatine, caffeine intake was associated with a faster rate of progression. In the current study, we investigated the association of caffeine with the rate of progression of PD and the interaction of this association with creatine intake. METHODS: Data were analyzed from a large phase 3 placebo-controlled clinical study of creatine as a potentially disease-modifying agent in PD. Subjects were recruited for this study from 45 movement disorders centers across the United States and Canada. A total of 1741 subjects with PD participated in the primary clinical study, and caffeine intake data were available for 1549 of these subjects. The association of caffeine intake with rate of progression of PD as measured by the change in the total Unified Parkinson Disease Rating Scale score and the interaction of this association with creatine intake were assessed. RESULTS: Caffeine intake was not associated with the rate of progression of PD in the main analysis, but higher caffeine intake was associated with significantly faster progression among subjects taking creatine. CONCLUSIONS: This is the largest and longest study conducted to date that addresses the association of caffeine with the rate of progression of PD. These data indicate a potentially deleterious interaction between caffeine and creatine with respect to the rate of progression of PD. PMID- 26366972 TI - The Value of 5-Aminolevulinic Acid in Low-grade Gliomas and High-grade Gliomas Lacking Glioblastoma Imaging Features: An Analysis Based on Fluorescence, Magnetic Resonance Imaging, 18F-Fluoroethyl Tyrosine Positron Emission Tomography, and Tumor Molecular Factors. AB - BACKGROUND: Approximately 20% of grade II and most grade III gliomas fluoresce after 5-aminolevulinic acid (5-ALA) application. Conversely, approximately 30% of nonenhancing gliomas are actually high grade. OBJECTIVE: The aim of this study was to identify preoperative factors (ie, age, enhancement, 18F-fluoroethyl tyrosine positron emission tomography [F-FET PET] uptake ratios) for predicting fluorescence in gliomas without typical glioblastomas imaging features and to determine whether fluorescence will allow prediction of tumor grade or molecular characteristics. METHODS: Patients harboring gliomas without typical glioblastoma imaging features were given 5-ALA. Fluorescence was recorded intraoperatively, and biopsy specimens collected from fluorescing tissue. World Health Organization (WHO) grade, Ki-67/MIB-1 index, IDH1 (R132H) mutation status, O-methylguanine DNA methyltransferase (MGMT) promoter methylation status, and 1p/19q co-deletion status were assessed. Predictive factors for fluorescence were derived from preoperative magnetic resonance imaging and F-FET PET. Classification and regression tree analysis and receiver-operating-characteristic curves were generated for defining predictors. RESULTS: Of 166 tumors, 82 were diagnosed as WHO grade II, 76 as grade III, and 8 as glioblastomas grade IV. Contrast enhancement, tumor volume, and F-FET PET uptake ratio >1.85 predicted fluorescence. Fluorescence correlated with WHO grade (P < .001) and Ki-67/MIB-1 index (P < .001), but not with MGMT promoter methylation status, IDH1 mutation status, or 1p19q co-deletion status. The Ki-67/MIB-1 index in fluorescing grade III gliomas was higher than in nonfluorescing tumors, whereas in fluorescing and nonfluorescing grade II tumors, no differences were noted. CONCLUSION: Age, tumor volume, and F-FET PET uptake are factors predicting 5-ALA-induced fluorescence in gliomas without typical glioblastoma imaging features. Fluorescence was associated with an increased Ki-67/MIB-1 index and high-grade pathology. Whether fluorescence in grade II gliomas identifies a subtype with worse prognosis remains to be determined. PMID- 26366973 TI - Serum MicroRNAs as Potential Biomarkers of AMD. AB - BACKGROUND: Age-related macular degeneration (AMD) is a major cause of blindness worldwide. Circulating microRNAs (miRNAs) in serum have emerged as novel candidate biomarkers for many diseases. The aim of the present study was to identify a serum microRNA (miRNA) expression profile specific for dry and wet forms of AMD. MATERIAL AND METHODS: Serum miRNA expression was first screened using TaqMan(r) Human MicroRNA Array A (Applied Biosystems). An extensive, self validated, individual, quantitative RT-PCR (qRT-PCR) study was then performed on a cohort of 300 AMD patients (150 wet form and 150 dry form) and 200 controls. The Mann-Whitney U test and nonparametric Spearman's rank correlation coefficient were used for statistical analysis. RESULTS: miRNA expression analysis revealed increased expression of miR661 and miR3121 in serum of patients with dry AMD and miR4258, miR889, and Let7 in patients with wet form. Expression of analyzed miRNA was not observed or remained at low level in controls. CONCLUSIONS: Differences in miRNA serum profile exist between patients with wet and dry form of AMD, which indicates miRNAs as potential biomarkers of AMD. Further studies should be performed to confirm its significance in clinical practice. PMID- 26366974 TI - Are children with asthma overconfident that they are using their inhalers correctly? AB - OBJECTIVE: The objectives of this study were to quantify the extent to which children with asthma are overconfident that they are using their inhalers correctly and determine whether demographic and clinical characteristics are associated with children being overconfident. METHODS: Children (n = 91) ages 7 17 with persistent asthma were recruited at two pediatric practices in North Carolina and demonstrated their inhaler technique for metered dose inhalers during an office visit. Children were dichotomized into two groups based on how confident they were that they were using their inhalers correctly: "completely confident" or "not completely confident". The mean number of inhaler steps (out of 8) children performed incorrectly was examined. We applied linear regression models for children in the "completely confident" group to determine whether demographic and clinical factors predicted their overconfidence, defined as the number of inhaler steps performed incorrectly. RESULTS: Children were primarily male (56%) and non-Hispanic White (60%). Sixty-eight (75%) children were "completely confident" that they were using their inhalers correctly. The "completely confident" group missed an average of 1.5 steps. In the "completely confident" group, males (p < 0.04) missed significantly more steps than females. The two most common errors were forgetting to shake the inhaler and holding their breath for 10 s. CONCLUSION: Regardless of their confidence level, children in our sample missed an average of 1-2 steps on an inhaler technique assessment. Findings from this study provide new evidence that it is insufficient to ask children if they are using their inhalers correctly. Therefore, it is vital that providers ask children to demonstrate their inhaler technique during health encounters. PMID- 26366976 TI - An exploratory study of the association between physical activity, cardiovascular fitness and body size in children with Down syndrome. AB - OBJECTIVE: To explore the association between physical activity, cardiovascular fitness and body size among children with Down syndrome. METHOD: Physical activity, cardiovascular fitness and body size were measured by accelerometry, maximal fitness test and anthropometric measurements (BMI, waist circumference), respectively. RESULTS: Fourteen children with Down syndrome (8 boys, 6 girls; mean age 12.9 years) participated. There was no significant correlation between physical activity and cardiovascular fitness or physical activity and body size. Children with Down syndrome who were fitter, had lower BMIs (r = -0.77, 95% confidence interval (CI) -0.41 to -0.93) and smaller waist circumference (r = 0.75, 95% CI -0.36 to -0.92). CONCLUSION: Preliminary evidence suggests physical activity may not be associated with either body size or fitness in children with Down syndrome. Body size appears to be inversely related to fitness in children with Down syndrome. PMID- 26366975 TI - Minireview: Were the IGF Signaling Inhibitors All Bad? AB - Preclinical studies in the 1980s defined a role for IGF signaling in the development and sustainability of the malignant process. Subsequently, antibody, tyrosine kinase, and ligand inhibitors of the IGF receptor were manufactured. In the past decade, numerous clinical trials have tested the efficacy of IGF receptor inhibitors in the treatment of advanced tumors. Early-phase trials in heavily pretreated populations showed promise with complete or partial responses in a few patients and stable disease in many more. Unfortunately, the results of the early-phase trials did not pan out to later-phase trials. The lack of use of biomarkers to define subsets of patients that may benefit from IGF receptor blockade and compensatory signaling via other growth factor receptors such as the insulin, GH, and epidermal growth factor receptors may have played a role in the lack of efficacy of IGF receptor inhibition in phase III trials. Although these trials failed to show benefit, the trials have revealed previously unknown knowledge regarding the complex nature of IGF signaling. The knowledge obtained from these trials will be useful in designing future trials studying inhibitors of growth factor signaling. PMID- 26366980 TI - The psychodynamics of borderline psychopathology. AB - The concept of borderline personality disorder (BPD) remains problematic despite psychiatrists' general familiarity with its DSM diagnostic criteria. The diagnosis of BPD is frequently based simply on the DSM checklist of traits and symptoms without knowledge of their origins or significance. Misdiagnosis is common, as is lack of recognition of the full complexity of this severe personality disorder and the nature of the vulnerabilities that underlie its myriad forms of pathology. The stresses of ordinary life are often too much for people with BPD. Knowledge of the nature and origins of their stress points, such as their great fear of loss or rejection, is necessary for adequate diagnosis and treatment. The author addresses how signature features of the disorder relate to psychosocial development, how they correlate with failed developmental milestones, and how they can be understood psychodynamically. This is essential knowledge for psychotherapists because the pathological interpersonal relationships of the borderline patient will be repeated and acted out in the transference, whatever the modality or intensity of treatment. PMID- 26366979 TI - Reliability and validity of the Stressful Life Events Screening Questionnaire among inpatients with severe neuropsychiatric illness. AB - The authors examined the reliability and concurrent validity of a modified version of the Stressful Life Events Screening Questionnaire (SLESQ) in a sample of 1,517 psychiatric inpatients characterized by serious mental illness. The scale showed a high level of internal consistency as well as a readily interpretable factor structure that differentiated sexual trauma from physical assaults and emotional distress. As well as revealing gender differences, the scale showed statistically significant but generally modest relationships between different aspects of trauma and diverse measures of psychopathology, including depression, anxiety, somatic symptoms, suicide attempts and self-harm, diminished well-being, functional disability, impaired emotion regulation, and limited experiential acceptance. The study extends prior normative research with the SLESQ based on samples of undergraduates to a large psychiatric sample and presents the first factor analysis of the instrument, lending further support to its clinical utility. PMID- 26366977 TI - Preparation of a Thermosensitive Gel Composed of a mPEG-PLGA-PLL-cRGD Nanodrug Delivery System for Pancreatic Tumor Therapy. AB - It is hypothesized that a gel (NP-Gel) composed of thermosensitive gel (Gel) and nanoparticles (NP) can prolong drug release time and overcome the drug resistance of pancreatic tumor cells. Paclitaxel (PTX)-loaded monomethoxy (polyethylene glycol)-poly(d,l-lactide-co-glycolide)-poly(l-lysine)-cyclic peptide (arginine glycine-aspartic-glutamic-valine acid) (mPEG-PLGA-PLL-cRGD) NP and NP-Gel were designed, optimized, and characterized using dynamic light scattering, transmission electron microscopy, high efficiency liquid chromatography, and rheological analyses. Aspc-1/PTX cell was used in a cell uptake test. A 3D cell model was used to mimic PTX elimination in tissue. The in vivo sustained release and antitumor effects were studied in Aspc-1/PTX-loaded nude mice with xerographic and in situ tumors. The NP were 133.7 +/- 28.3 nm with 85.03% entrapped efficiency, 1.612% loaded ratio, and suitable rheological properties. PTX was released as NP from NP-Gel, greatly prolonging the release and elimination times to afford long-term effects. NP-Gel enhanced the uptake of PTX by Aspc-1/PTX cells more than using NP or the Gel alone. Gel and NP-Gel remained solid in the tumor and stayed over 50 days versus the several days of NP in solution. NP-Gel exhibited a much higher inhibition rate in vivo than in solution, NP, or the Gel alone. In conclusion, the antitumor effects of NP-Gel might arise from synergic effects from NP and the Gel. NP primarily reversed drug resistance, while the Gel prolonged release time considerably in situ. This preparation proved effective with a very small PTX dose (250 MUg/kg) and exhibited few toxic effects in normal tissue. PMID- 26366981 TI - Development of a structure-validated Family Relationship Questionnaire (FRQ) with Chinese university students. AB - Consistent results have shown a relationship between the psychological world of children and their perceived parental bonding or family attachment style, but to date there is no single measure covering both styles. The authors designed a statement matrix with 116 items for this purpose and compared it with the Parental Bonding Instrument (PBI) in a study with 718 university students. After exploratory and confirmatory factor analyses, five factors (scales)--namely, Paternal/Maternal Encouragement (5 items each), Paternal/Maternal Abuse (5 items each), Paternal/Maternal Freedom Release (5 items each), General Attachment (5 items), and Paternal/Maternal Dominance (4 items each)--were defined to form a Family Relationship Questionnaire (FRQ). The internal alphas of the factors ranged from .64 to .83, and their congruency coefficients were .93 to .98 in samples regarding father and mother. Women scored significantly higher on FRQ General Attachment and Maternal Encouragement and lower on Paternal Abuse than men did; only children scored significantly higher on Paternal and Maternal Encouragements than children with siblings did. Women also scored significantly higher on PBI Paternal Autonomy Denial; only children scored significantly higher on Paternal and Maternal Cares and Maternal Autonomy Denial. All intercorrelations between FRQ scales were low to medium, and some correlations between FRQ and PBI scales were medium to high. This study demonstrates that the FRQ has a structure of five factors with satisfactory discriminant and convergent validities, which might help to characterize family relationships in healthy and clinical populations. PMID- 26366978 TI - Vaccination uptake by vaccine-hesitant parents attending a specialist immunization clinic in Australia. AB - Vaccine hesitancy (VH) is an issue of global concern. The quality of communication between healthcare providers and parents can influence parental immunization acceptance. We aimed to describe immunization uptake following specialist immunization clinic (SIC) consultation for Australian children of VH parents as a cohort, and according to pre-clinic parental position on immunization. At a single tertiary pediatric SIC (RCH, Melbourne) a retrospective descriptive study classified VH families according to 3 proposed parental positions on immunization at initial clinic attendance. Immunization status at follow up was ascertained via the Australian Children's Immunization Register and National HPV Program Register and compared between groups. Of the VH cohort, 13/38 (34%) families were classified as hesitant, 21 (55%) as late/selective vaccinators and 4 (11%) as vaccine refusers. Mean follow up post-SIC attendance was 14.5 months. For the overall VH cohort, the majority chose selective immunization (42%) following SIC consultation. When analyzed by pre-clinic parental position on immunization, there was a trend for hesitant families to proceed with full immunization, selective families to continue selective immunization and refusing families to remain unimmunised (p < 0.0001). The most commonly omitted vaccines were hepatitis B (66%) and Haemophilus influenzae type B (55%), followed by the meningococcal C conjugate vaccine (53%) and measles, mumps and rubella vaccine (53%). Immunization outcome appears to correlate with pre-clinic parental position on immunization for the majority of families attending a SIC in Australia, with selective immunization the most common outcome. Tailored communication approaches based on parental position on immunization may optimise clinic resources and engagement of families, but require prospective research evaluation. PMID- 26366982 TI - The give and take of freedom: The role of involuntary hospitalization and treatment in recovery from mental illness. AB - The authors reviewed and synthesized scholarly literature on the topic of involuntary confinement and treatment for severely mentally ill adults. Objectively, all facets of the issue are reported, including recurrent positive outcomes, negative outcomes, and patient experiences in common. Patient experiences are organized into related subthemes of autonomy, patient satisfaction, relationships with staff, perceived coercion, traumatization, and humiliation. The literature suggests that short-term involuntary hospitalization is sometimes necessary in order to prevent the mentally ill from psychiatrically decompensating or harming themselves or others. Understandably, hospitalization is often experienced by the mentally ill as a demoralizing violation of their rights and tends to lead them to disengage further from the professional help they need in order to recover. In turn, disengagement leads to further decompensation and resulting risk for rehospitalization. In order to intervene in this cycle and instill severely mentally ill patients with hope in the recovery process, the use of coercive tactics must be decreased in favor of cooperative engagement measures to the greatest extent possible. Patients must be empowered to make choices within the limits of their illnesses through positive interactions with staff, particularly in potentially negative, autonomy compromising situations. Cooperative measures may help to minimize the potentially traumatic and humiliating effects of being involuntarily hospitalized and medicated. In turn, trusting patient-provider relationships may develop. Thereafter, the severely mentally ill may become more likely to seek professional help on their own volition in the future. PMID- 26366985 TI - Difficulties Faced by Patients Suffering from Total Bilateral Vestibular Loss. AB - A unilateral sudden loss of function generates intense and frightening symptoms urging patients to see a doctor. Generally, the symptoms and signs of the deficit are so obvious that doctors make the diagnosis quickly. The situation is quite different if the deficit is gradual and affects both sides. To better understand the difficulties faced by patients suffering from total bilateral vestibular loss, 19 subjects were interviewed in a semistructured talk. The discussion focused on five main topics: (1) symptoms, (2) the medical trajectory from the earliest symptoms to the diagnosis, (3) the prescribed treatments, (4) the impact of the disease on work, and (5) the impact on social functioning and recreational activities. The symptoms reported by patients are insidious, and they may suggest a neurological deficit or a cardiocirculatory or psychiatric disorder. The diagnosis is often made after several consultations with several doctors from different specialties. When the diagnosis is made, all kinds of treatment are undertaken, in particular vestibular rehabilitation. Indeed, most physicians believe that it can promote central compensation processes, even though it has been demonstrated that vestibular exercises are ineffective in most of these patients. Two thirds of our subjects were obliged to modify or even stop their professional activities due the bilateral vestibular loss. In some patients, the disability is such that they almost constantly require the presence of their spouse. In conclusion, the symptoms of bilateral vestibular loss are sometimes misleading. They are often not recognized by doctors. The deficit has an obvious impact on patients' social functioning and professional activities. PMID- 26366984 TI - Racial Disparities in Pain Management of Children With Appendicitis in Emergency Departments. AB - IMPORTANCE: Racial disparities in use of analgesia in emergency departments have been previously documented. Further work to understand the causes of these disparities must be undertaken, which can then help inform the development of interventions to reduce and eradicate racial disparities in health care provision. OBJECTIVE: To evaluate racial differences in analgesia administration, and particularly opioid administration, among children diagnosed as having appendicitis. DESIGN, SETTING, AND PARTICIPANTS: Repeated cross-sectional study of patients aged 21 years or younger evaluated in the emergency department who had an International Classification of Diseases, Ninth Revision diagnosis of appendicitis, using the National Hospital Ambulatory Medical Care Survey from 2003 to 2010. We calculated the frequency of both opioid and nonopioid analgesia administration using complex survey weighting. We then performed multivariable logistic regression to examine racial differences in overall administration of analgesia, and specifically opioid analgesia, after adjusting for important demographic and visit covariates, including ethnicity and pain score. MAIN OUTCOMES AND MEASURES: Receipt of analgesia administration (any and opioid) by race. RESULTS: An estimated 0.94 (95% CI, 0.78-1.10) million children were diagnosed as having appendicitis. Of those, 56.8% (95% CI, 49.8%-63.9%) received analgesia of any type; 41.3% (95% CI, 33.7%-48.9%) received opioid analgesia (20.7% [95% CI, 5.3%-36.0%] of black patients vs 43.1% [95% CI, 34.6%-51.4%] of white patients). When stratified by pain score and adjusted for ethnicity, black patients with moderate pain were less likely to receive any analgesia than white patients (adjusted odds ratio = 0.1 [95% CI, 0.02-0.8]). Among those with severe pain, black patients were less likely to receive opioids than white patients (adjusted odds ratio = 0.2 [95% CI, 0.06-0.9]). In a multivariable model, there were no significant differences in the overall rate of analgesia administration by race. However, black patients received opioid analgesia significantly less frequently than white patients (12.2% [95% CI, 0.1%-35.2%] vs 33.9% [95% CI, 0.6% 74.9%], respectively; adjusted odds ratio = 0.2 [95% CI, 0.06-0.8]). CONCLUSIONS AND RELEVANCE: Appendicitis pain is undertreated in pediatrics, and racial disparities with respect to analgesia administration exist. Black children are less likely to receive any pain medication for moderate pain and less likely to receive opioids for severe pain, suggesting a different threshold for treatment. PMID- 26366987 TI - WASP: allele-specific software for robust molecular quantitative trait locus discovery. AB - Allele-specific sequencing reads provide a powerful signal for identifying molecular quantitative trait loci (QTLs), but they are challenging to analyze and are prone to technical artifacts. Here we describe WASP, a suite of tools for unbiased allele-specific read mapping and discovery of molecular QTLs. Using simulated reads, RNA-seq reads and chromatin immunoprecipitation sequencing (ChIP seq) reads, we demonstrate that WASP has a low error rate and is far more powerful than existing QTL-mapping approaches. PMID- 26366986 TI - Real-time metabolome profiling of the metabolic switch between starvation and growth. AB - Metabolic systems are often the first networks to respond to environmental changes, and the ability to monitor metabolite dynamics is key for understanding these cellular responses. Because monitoring metabolome changes is experimentally tedious and demanding, dynamic data on time scales from seconds to hours are scarce. Here we describe real-time metabolome profiling by direct injection of living bacteria, yeast or mammalian cells into a high-resolution mass spectrometer, which enables automated monitoring of about 300 compounds in 15-30 s cycles over several hours. We observed accumulation of energetically costly biomass metabolites in Escherichia coli in carbon starvation-induced stationary phase, as well as the rapid use of these metabolites upon growth resumption. By combining real-time metabolome profiling with modeling and inhibitor experiments, we obtained evidence for switch-like feedback inhibition in amino acid biosynthesis and for control of substrate availability through the preferential use of the metabolically cheaper one-step salvaging pathway over costly ten-step de novo purine biosynthesis during growth resumption. PMID- 26366988 TI - Molecular Endoscopy and in vivo Imaging in Inflammatory Bowel Diseases. AB - BACKGROUND: Studies in recent years have shown that standard imaging modalities such as endoscopy, ultrasonography or MRI are essential for assessment of gut inflammation in patients with inflammatory bowel diseases (IBDs). In addition, endoscopy plays a pivotal role in the analysis of mucosal healing in these disorders. However, these techniques do not allow a detailed analysis of the molecular pathways driving gut inflammation in IBD patients. Here, we discuss the role of new techniques for the molecular imaging of gut inflammation in IBD with special reference to the prediction of responses to therapy using antibodies to tumor necrosis factor (anti-TNF). Key Messages: Several in vivo imaging studies have been performed in IBD patients before and after anti-TNF therapy. In one study, (99m)Technetium-labeled annexin V was given to patients with active Crohn's disease before and after anti-TNF therapy with infliximab. Subsequently, single-photon emission CT (SPECT) was performed to study the effect of anti-TNF treatment on apoptosis in the intestine during active colitis. This study showed enrichment of technetium signals in the gut of patients who responded to anti-TNF therapy. The findings suggested that anti-TNF treatment induces T-cell apoptosis in vivo and that SPECT imaging can be used for prediction of response to anti-TNF therapy. In another study, fluorescent anti-TNF antibodies (fluorescent adalimumab) were chosen for molecular imaging during confocal laser endomicroscopy in patients with active Crohn's disease. This study revealed that an increase of membrane-bound TNF expressing mucosal immune cells predicts response to subsequent adalimumab therapy. CONCLUSIONS: Molecular in vivo imaging is an exciting new field in patients with IBD. It is expected that this field will allow new insights into the pathophysiology of IBD and may be used for personalized medicine in the future. PMID- 26366989 TI - Monolayer to interdigitated partial bilayer smectic C transition in thiophene based spacer mesogens: X-ray diffraction and (13)C nuclear magnetic resonance studies. AB - Mesophase organization of molecules built with thiophene at the center and linked via flexible spacers to rigid side arm core units and terminal alkoxy chains has been investigated. Thirty homologues realized by varying the span of the spacers as well as the length of the terminal chains have been studied. In addition to the enantiotropic nematic phase observed for all the mesogens, the increase of the spacer as well as the terminal chain lengths resulted in the smectic C phase. The molecular organization in the smectic phase as investigated by temperature dependent X-ray diffraction measurements revealed an interesting behavior that depended on the length of the spacer vis-a-vis the length of the terminal chain. Thus, a tilted interdigitated partial bilayer organization was observed for molecules with a shorter spacer length, while a tilted monolayer arrangement was observed for those with a longer spacer length. High-resolution solid state (13)C NMR studies carried out for representative mesogens indicated a U-shape for all the molecules, indicating that intermolecular interactions and molecular dynamics rather than molecular shape are responsible for the observed behavior. Models for the mesophase organization have been considered and the results understood in terms of segregation of incompatible parts of the mesogens combined with steric frustration leading to the observed lamellar order. PMID- 26366990 TI - An overview of age estimation in forensic anthropology: perspectives and practical considerations. AB - CONTEXT: Information on methods of age estimation in physical anthropology, in particular with regard to age-at-death from human skeletal remains, is widely available in the literature. However, the practicalities and real challenges faced in forensic casework are not always highlighted. OBJECTIVES: To provide a practitioner's perspective, regarding age estimation in forensic anthropology (both in the living as well as the dead), with an emphasis on the types of cases, the value of such work and its challenges and limitations. METHODS: The paper reviews the current literature on age estimation with a focus on forensic anthropology, but it also brings the author's personal perspective derived from a number of forensic cases. RESULTS AND CONCLUSIONS: Although much is known about what methods to use, but not always how to apply them, little attention has been given in the literature to the real practicalities faced by forensic anthropologists, for example: the challenges in different types of scenarios; how to report age estimations; responsibilities; and ethical concerns. This paper gathers some of these aspects into one overview which includes the value of such work and the practical challenges, not necessarily with the methods themselves, but also with regard to how these are applied in the different cases where age estimation is required. PMID- 26366991 TI - Neutral and cationic pyridylbutadienes: solvatochromism and fluorescence response with sodium cholate. AB - Neutral and cationic diarylbutadienes with pyridine and pyridinium groups as electron acceptors with dimethylamine and diphenylamine as electron donors were synthesized. The absorption and emission properties of these dienes were investigated in homogeneous organic solvents and in sodium cholate media. In strongly polar solvents, both neutral and cationic fluorophores exhibit a bathochromic shift of emission characteristics of intramolecular charge transfer (ICT) excited states. The presence of a strongly electron withdrawing pyridinium group induces large absorption (~480 nm) and emission wavelength shifts (near ~680 nm) in polar solvents. This solvatochromic behavior is utilized as a tool to examine the fluorophore-sodium cholate interaction. Significant hypsochromic emission shifts (up to ~66 nm) and concomitant intensity enhancement (up to 32 fold) are seen for these fluorophores in the presence of increasing concentrations of sodium cholate. Fluorescence lifetime measurements reveal biexponential decay patterns indicating the binding of molecules in distinct cholate environments. PMID- 26366992 TI - OsMAPK6, a mitogen-activated protein kinase, influences rice grain size and biomass production. AB - Grain size is an important agronomic trait in determining grain yield. However, the molecular mechanisms that determine the final grain size are not well understood. Here, we report the functional analysis of a rice (Oryza sativa L.) mutant, dwarf and small grain1 (dsg1), which displays pleiotropic phenotypes, including small grains, dwarfism and erect leaves. Cytological observations revealed that the small grain and dwarfism of dsg1 were mainly caused by the inhibition of cell proliferation. Map-based cloning revealed that DSG1 encoded a mitogen-activated protein kinase (MAPK), OsMAPK6. OsMAPK6 was mainly located in the nucleus and cytoplasm, and was ubiquitously distributed in various organs, predominately in spikelets and spikelet hulls, consistent with its role in grain size and biomass production. As a functional kinase, OsMAPK6 interacts strongly with OsMKK4, indicating that OsMKK4 is likely to be the upstream MAPK kinase of OsMAPK6 in rice. In addition, hormone sensitivity tests indicated that the dsg1 mutant was less sensitive to brassinosteroids (BRs). The endogenous BR levels were reduced in dsg1, and the expression of several BR signaling pathway genes and feedback-inhibited genes was altered in the dsg1 mutant, with or without exogenous BRs, indicating that OsMAPK6 may contribute to influence BR homeostasis and signaling. Thus, OsMAPK6, a MAPK, plays a pivotal role in grain size in rice, via cell proliferation, and BR signaling and homeostasis. PMID- 26366993 TI - How do non-covalent complexes dissociate in droplets? A case study of the desolvation of dsDNA from a charged aqueous nanodrop. AB - We present the desolvation mechanism of a double-stranded oligodeoxynucleotide (dsDNA) from an aqueous nanodrop studied by using atomistic molecular dynamics methods. The central theme of this study is the stability of a non-covalently bound complex, in general, and that of a dsDNA in particular, in a droplet environment. Among the factors that may affect the stability of a complex in an evaporating droplet we examine the increase in ion concentration and the distinct droplet morphologies arising from the charge-induced instability. We explore in detail a large set of aqueous nanodrops with excess negative charge, which comprise a dsDNA and Na(+), Cl(-) ions at various concentrations. We find that for a square of the charge to volume ratio above that of the Rayleigh limit the droplet attains distinct "spiky" morphologies that disperse the charge in larger volume relative to that of the spherical drop. Moreover, it is found that it is possible for a non-covalent complex to remain associated in an unstable droplet as long as there is enough solvent to accommodate the instability. In the presence of Na(+) and Cl(-) ions, the Na(+) ions form adducts with the double helical DNA in the minor groove, which help stabilise the duplex state in the gas phase. The negative ions may be released from the droplet. In a DNA-containing droplet with a net charge that is less negative than 50% of the dsDNA charge, the DNA maintains a double-stranded state in the gas phase. Several of our findings are in good agreement with experiments, while the spiky droplet morphology due to the charge-induced instability calls for new experiments. The results shed light on the association properties of complexes of macromolecules in droplet environments, which are critical intermediates in electrospray ionisation experiments. PMID- 26366994 TI - Vascularized axillary lymph node transfer: A novel model in the rat. AB - Vascularized lymph node transfer (VLNT) is a promising microvascular free flap technique for the surgical treatment of lymphedema. To date, few experimental animal models for VLNT have been described and the viability of lymph nodes after the transfer tested. We aimed to evaluate the feasibility of axillary VLNT in the rat. Lymph node containing flaps were harvested from the axillary region in 10 Lewis rats based on the axillary vessels. Flaps were transferred to the ipsilateral groin and end-to-side microanastomosis was performed to the femoral vessels using 10-0 sutures. Indocyanine green (ICG) angiography was used to confirm flap perfusion. On postoperative day 7, flaps were elevated to assess their structure and vessel patency. Hematoxylin and eosin staining was used to confirm the presence and survival of lymph nodes. All animals tolerated the procedure well. Immediate post-procedure ICG angiography confirmed flap perfusion. No signs of ischemia or necrosis were observed in donor extremities. At postoperative day 7, all flaps remained viable with patent vascular pedicles. Gross examination and histology confirmed the presence of 3.6 +/- 0.5 lymph nodes in each flap without any signs of necrosis. This study showed that the transfer of axillary lymph nodes based on the axillary vessels is feasible. The flap can be used without the need for donor animals and it contains a consistent number of lymph nodes. This reliable VLNT can be further utilized in studies involving lymphedema, transplantation, and induction of immunologic tolerance. PMID- 26366996 TI - Correction: Rapid and Localized Mechanical Stimulation and Adhesion Assay: TRPM7 Involvement in Calcium Signaling and Cell Adhesion. PMID- 26366995 TI - Validation of Reference Genes for RT-qPCR Analysis in Noise-Induced Hearing Loss: A Study in Wistar Rat. AB - The reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) requires adequate normalization in order to ensure accurate results. The use of reference genes is the most common method to normalize RT-qPCR assays; however, many studies have reported that the expression of frequently used reference genes is more variable than expected, depending on experimental conditions. Consequently, proper validation of the stability of reference genes is an essential step when performing new gene expression studies. Despite the fact that RT-qPCR has been widely used to elucidate molecular correlates of noise-induced hearing loss (NIHL), up to date there are no reports demonstrating validation of reference genes for the evaluation of changes in gene expression after NIHL. Therefore, in this study we evaluated the expression of some commonly used reference genes (Arbp, b-Act, b2m, CyA, Gapdh, Hprt1, Tbp, Tfrc and UbC) and examined their suitability as endogenous control genes for RT-qPCR analysis in the adult Wistar rat in response to NIHL. Four groups of rats were noise-exposed to generate permanent cochlear damage. Cochleae were collected at different time points after noise exposure and the expression level of candidate reference genes was evaluated by RT-qPCR using geNorm, NormFinder and BestKeeper software to determine expression stability. The three independent applications revealed Tbp as the most stably expressed reference gene. We also suggest a group of top ranked reference genes that can be combined to obtain suitable reference gene pairs for the evaluation of the effects of noise on gene expression in the cochlea. These findings provide essential basis for further RT-qPCR analysis in studies of NIHL using Wistar rats as animal model. PMID- 26366997 TI - Water-Exchange-Modified Kinetic Parameters from Dynamic Contrast-Enhanced MRI as Prognostic Biomarkers of Survival in Advanced Hepatocellular Carcinoma Treated with Antiangiogenic Monotherapy. AB - BACKGROUND: To find prognostic biomarkers in pretreatment dynamic contrast enhanced MRI (DCE-MRI) water-exchange-modified (WX) kinetic parameters for advanced hepatocellular carcinoma (HCC) treated with antiangiogenic monotherapy. METHODS: Twenty patients with advanced HCC underwent DCE-MRI and were subsequently treated with sunitinib. Pretreatment DCE-MRI data on advanced HCC were analyzed using five different WX kinetic models: the Tofts-Kety (WX-TK), extended TK (WX-ETK), two compartment exchange, adiabatic approximation to tissue homogeneity (WX-AATH), and distributed parameter (WX-DP) models. The total hepatic blood flow, arterial flow fraction (gamma), arterial blood flow (BFA), portal blood flow, blood volume, mean transit time, permeability-surface area product, fractional interstitial volume (vI), extraction fraction, mean intracellular water molecule lifetime (tauC), and fractional intracellular volume (vC) were calculated. After receiver operating characteristic analysis with leave one-out cross-validation, individual parameters for each model were assessed in terms of 1-year-survival (1YS) discrimination using Kaplan-Meier analysis, and association with overall survival (OS) using univariate Cox regression analysis with permutation testing. RESULTS: The WX-TK-model-derived gamma (P = 0.022) and vI (P = 0.010), and WX-ETK-model-derived tauC (P = 0.023) and vC (P = 0.042) were statistically significant prognostic biomarkers for 1YS. Increase in the WX-DP model-derived BFA (P = 0.025) and decrease in the WX-TK, WX-ETK, WX-AATH, and WX DP-model-derived vC (P = 0.034, P = 0.038, P = 0.028, P = 0.041, respectively) were significantly associated with an increase in OS. CONCLUSIONS: The WX-ETK model-derived vC was an effective prognostic biomarker for advanced HCC treated with sunitinib. PMID- 26366998 TI - Increased Risk of Coronary Heart Disease in Patients with Primary Fibromyalgia and Those with Concomitant Comorbidity-A Taiwanese Population-Based Cohort Study. AB - OBJECTIVES: Fibromyalgia has seldom been associated with coronary heart disease (CHD). The aim of this study was to evaluate the risk of CHD in patients with fibromyalgia. METHODS: We used a dataset of one million participants, systemically scrambled from the Taiwanese national insurance beneficiaries, to identify 61,612 patients with incident fibromyalgia (ICD-9-CM 729.0-729.1) and 184,834 reference subjects matched by sex, age and index date of diagnosis in a 1:3 ratio from 2000 to 2005, with a mean 8.86 +/- 2.68 years of follow-up until 2011. Risk of CHD was analyzed by Cox proportional hazard modeling. RESULTS: Patients with fibromyalgia had a mean age of 44.1 +/- 16.5 years. CHD events developed in fibromyalgia patients (n = 8,280; 15.2 per 103 person-years) and reference subjects (n = 15,162; 9.26 per 103 person-years) with a significant incidence rate ratio of 1.64 (95% confidence interval: 1.61-1.68). The adjusted hazard ratio for CHD in fibromyalgia patients relative to reference subjects was 1.47 (1.43-1.51), after adjusting for age, gender, occupation, monthly income, traditional cardiovascular comorbidities, depression and anxiety. We noted that fibromyalgia and cardiovascular comorbidities had a significant interaction effect on CHD risk (p for interaction <0.01), which was markedly enhanced in fibromyalgia patients with concomitant comorbidities relative to patients with primary fibromyalgia and reference subjects (no fibromyalgia, no comorbidity). CONCLUSIONS: Our report shows that fibromyalgia patients have an independent risk for CHD development. Fibromyalgia patients with concomitant comorbidities have markedly increased CHD risk relative to those with primary fibromyalgia. PMID- 26366999 TI - IL-10 Protects Neurites in Oxygen-Glucose-Deprived Cortical Neurons through the PI3K/Akt Pathway. AB - IL-10, as a cytokine, has an anti-inflammatory cascade following various injuries, but it remains blurred whether IL-10 protects neurites of cortical neurons after oxygen-glucose deprivation injury. Here, we reported that IL-10, in a concentration-dependent manner, reduced neuronal apoptosis and increased neuronal survival in oxygen-glucose-deprived primary cortical neurons, producing an optimal protective effect at 20ng/ml. After staining NF-H and GAP-43, we found that IL-10 significantly protected neurites in terms of axon length and dendrite number by confocal microscopy. Furthermore, it induced the phosphorylation of AKT, suppressed the activation of caspase-3, and up-regulated the protein expression of GAP-43. In contrast, LY294002, a specific inhibitor of PI3K/AKT, reduced the level of AKT phosphorylation and GAP-43 expression, increased active caspase-3 expression and thus significantly weakened IL-10-mediated protective effect in the OGD-induced injury model. IL-10NA, the IL-10 neutralizing antibody, reduced the level of p-PI3K phosphorylation and increased the expression of active caspase-3. These findings suggest that IL-10 provides neuroprotective effects by protecting neurites through PI3K/AKT signaling pathway in oxygen glucose-deprived primary cortical neurons. PMID- 26367000 TI - A Computational Gene Expression Score for Predicting Immune Injury in Renal Allografts. AB - BACKGROUND: Whole genome microarray meta-analyses of 1030 kidney, heart, lung and liver allograft biopsies identified a common immune response module (CRM) of 11 genes that define acute rejection (AR) across different engrafted tissues. We evaluated if the CRM genes can provide a molecular microscope to quantify graft injury in acute rejection (AR) and predict risk of progressive interstitial fibrosis and tubular atrophy (IFTA) in histologically normal kidney biopsies. METHODS: Computational modeling was done on tissue qPCR based gene expression measurements for the 11 CRM genes in 146 independent renal allografts from 122 unique patients with AR (n = 54) and no-AR (n = 92). 24 demographically matched patients with no-AR had 6 and 24 month paired protocol biopsies; all had histologically normal 6 month biopsies, and 12 had evidence of progressive IFTA (pIFTA) on their 24 month biopsies. Results were correlated with demographic, clinical and pathology variables. RESULTS: The 11 gene qPCR based tissue CRM score (tCRM) was significantly increased in AR (5.68 +/- 0.91) when compared to STA (1.29 +/- 0.28; p < 0.001) and pIFTA (7.94 +/- 2.278 versus 2.28 +/- 0.66; p = 0.04), with greatest significance for CXCL9 and CXCL10 in AR (p <0.001) and CD6 (p<0.01), CXCL9 (p<0.05), and LCK (p<0.01) in pIFTA. tCRM was a significant independent correlate of biopsy confirmed AR (p < 0.001; AUC of 0.900; 95% CI = 0.705-903). Gene expression modeling of 6 month biopsies across 7/11 genes (CD6, INPP5D, ISG20, NKG7, PSMB9, RUNX3, and TAP1) significantly (p = 0.037) predicted the development of pIFTA at 24 months. CONCLUSIONS: Genome-wide tissue gene expression data mining has supported the development of a tCRM-qPCR based assay for evaluating graft immune inflammation. The tCRM score quantifies injury in AR and stratifies patients at increased risk of future pIFTA prior to any perturbation of graft function or histology. PMID- 26367001 TI - Effect of Trimetazidine in Patients Undergoing Percutaneous Coronary Intervention: A Meta-Analysis. AB - Optimizing the metabolism of the myocardium is a new strategy for patients with ischemic heart disease. Many studies have reported beneficial effects of trimetazidine (TMZ) on the clinical prognosis of patients with ischemic heart disease, but whether these beneficial effects are extended to patients undergoing percutaneous coronary intervention (PCI) remains uncertain. A meta-analysis was performed to evaluate the effect of TMZ on patients undergoing PCI. We conducted an electronic search of PubMed, Cochrane databases, the China National Knowledge Infrastructure, and Chinese Biological Medicine Database to identify randomized controlled trials. Methodological quality was assessed according to the Jadad scale score, and the meta-analysis was performed using Cochrane Collaboration RevMan 5.2 and Comprehensive Meta-Analysis. Dichotomous data were analyzed using relative risk (RR) or odds ratio (OR) with effect size indicated by the 95% confidence interval (CI), and continuous variables were analyzed using weighted mean differences (WMD) with effect size indicated by the 95% CI. Sensitivity analysis was performed by changing the statistical methods and effect model. Nine studies involving a total of 778 patients were included in this meta-analysis. Additional use of TMZ significantly improved the left ventricular ejection fraction (WMD: 3.11, 95% CI: [2.26, 3.96]) and reduced elevated cardiac troponin Ic level (RR: 0.69, 95% CI: [0.48, 0.99]), angina attacks during PCI (OR: 0.16, 95% CI: [0.07, 0.38]), and ischemic ST-T changes on the echocardiogram during PCI (RR: 0.76, 95% CI: [0.59, 0.98]). However, no significant difference was observed in serum BNP level 30 days after PCI between the experimental and control group. Additional use of TMZ for patients undergoing PCI may reduce myocardial injury during the procedure and improve cardiac function. PMID- 26367002 TI - Live Poultry Exposure and Public Response to Influenza A(H7N9) in Urban and Rural China during Two Epidemic Waves in 2013-2014. AB - BACKGROUND: The novel influenza A(H7N9) virus has caused 2013 spring and 2013 2014 winter waves of human infections since its first emergence in China in March 2013. Exposure to live poultry is a risk factor for H7N9 infection. Public psychobehavioral responses often change during progression of an epidemic. METHODS: We conducted population-based surveys in southern China to examine human exposure to live poultry, and population psychological response and behavioral changes in the two waves. In Guangzhou, an urban area of Guangdong province, we collected data using telephone surveys with random digit dialing in May-June 2013 and again in December 2013 to January 2014. In Zijin county, a rural area of the same province, we used door-to-door surveys under a stratified sampling design in July 2013 and again in December 2013 to January 2014. All responses were weighted by age and sex to the respective adult populations. FINDINGS: Around half of the urban respondents (53.8%) reported having visited LPMs in the previous year in the first survey, around double that reported in the second survey (27.7%). In the rural surveys, around half of the participants reported raising backyard poultry in the past year in the first survey, increasing to 83.2% participants in the second survey. One third of urban subjects supported the permanent closure of LPMs in the first and second surveys, and factors associated with support for closure included female sex, higher level of worry towards H7N9, and worry induced by a hypothetical influenza-like illness. CONCLUSIONS: Our study indicated high human exposure to live poultry and low support for permanent closure of markets in both urban and rural residents regardless of increased worry during the epidemic. PMID- 26367003 TI - Nasal Lipopolysaccharide Challenge and Cytokine Measurement Reflects Innate Mucosal Immune Responsiveness. AB - BACKGROUND: Practical methods of monitoring innate immune mucosal responsiveness are lacking. Lipopolysaccharide (LPS) is a component of the cell wall of Gram negative bacteria and a potent activator of Toll-like receptor (TLR)-4. To measure LPS responsiveness of the nasal mucosa, we administered LPS as a nasal spray and quantified chemokine and cytokine levels in mucosal lining fluid (MLF). METHODS: We performed a 5-way cross-over, single blind, placebo-controlled study in 15 healthy non-atopic subjects (n = 14 per protocol). Doses of ultrapure LPS (1, 10, 30 or 100MUg/100MUl) or placebo were administered by a single nasal spray to each nostril. Using the recently developed method of nasosorption with synthetic adsorptive matrices (SAM), a series of samples were taken. A panel of seven cytokines/chemokines were measured by multiplex immunoassay in MLF. mRNA for intercellular cell adhesion molecule-1 (ICAM-1) was quantified from nasal epithelial curettage samples taken before and after challenge. RESULTS: Topical nasal LPS was well tolerated, causing no symptoms and no visible changes to the nasal mucosa. LPS induced dose-related increases in MLF levels of IL-1beta, IL-6, CXCL8 (IL-8) and CCL3 (MIP-1alpha) (AUC at 0.5 to 10h, compared to placebo, p<0.05 at 30 and 100MUg LPS). At 100MUg LPS, IL-10, IFN-alpha and TNF-alpha were also increased (p<0.05). Dose-related changes in mucosal ICAM-1 mRNA were also seen after challenge, and neutrophils appeared to peak in MLF at 8h. However, 2 subjects with high baseline cytokine levels showed prominent cytokine and chemokine responses to relatively low LPS doses (10MUg and 30MUg LPS). CONCLUSIONS: Topical nasal LPS causes dose-dependent increases in cytokines, chemokines, mRNA and cells. However, responsiveness can show unpredictable variations, possibly because baseline innate tone is affected by environmental factors. We believe that this new technique will have wide application in the study of the innate immune responses of the respiratory mucosa. KEY MESSAGES: Ultrapure LPS was used as innate immune stimulus in a human nasal challenge model, with serial sampling of nasal mucosal lining fluid (MLF) by nasosorption using a synthetic absorptive matrix (SAM), and nasal curettage of mucosal cells. A dose response could be demonstrated in terms of levels of IL-1beta, IL-6, CXCL8 and CCL3 in MLF, as well as ICAM-1 mRNA in nasal curettage specimens, and levels of neutrophils in nasal lavage. Depending on higher baseline levels of inflammation, there were occasional magnified innate inflammatory responses to LPS. TRIAL REGISTRATION: Clinical Trials.gov NCT02284074. PMID- 26367004 TI - Ecosystem Engineering by Plants on Wave-Exposed Intertidal Flats Is Governed by Relationships between Effect and Response Traits. AB - In hydrodynamically stressful environments, some species--known as ecosystem engineers--are able to modify the environment for their own benefit. Little is known however, about the interaction between functional plant traits and ecosystem engineering. We studied the responses of Scirpus tabernaemontani and Scirpus maritimus to wave impact in full-scale flume experiments. Stem density and biomass were used to predict the ecosystem engineering effect of wave attenuation. Also the drag force on plants, their bending angle after wave impact and the stem biomechanical properties were quantified as both responses of stress experienced and effects on ecosystem engineering. We analyzed lignin, cellulose, and silica contents as traits likely effecting stress resistance (avoidance, tolerance). Stem density and biomass were strong predictors for wave attenuation, S. maritimus showing a higher effect than S. tabernaemontani. The drag force and drag force per wet frontal area both differed significantly between the species at shallow water depths (20 cm). At greater depths (35 cm), drag forces and bending angles were significantly higher for S. maritimus than for S. tabernaemontani. However, they do not differ in drag force per wet frontal area due to the larger plant surface of S. maritimus. Stem resistance to breaking and stem flexibility were significantly higher in S. tabernaemontani, having a higher cellulose concentration and a larger cross-section in its basal stem parts. S. maritimus had clearly more lignin and silica contents in the basal stem parts than S. tabernaemontani. We concluded that the effect of biomass seems more relevant for the engineering effect of emergent macrophytes with leaves than species morphology: S. tabernaemontani has avoiding traits with minor effects on wave attenuation; S. maritimus has tolerating traits with larger effects. This implies that ecosystem engineering effects are directly linked with traits affecting species stress resistance and responding to stress experienced. PMID- 26367005 TI - Anoxic Biodegradation of Isosaccharinic Acids at Alkaline pH by Natural Microbial Communities. AB - One design concept for the long-term management of the UK's intermediate level radioactive wastes (ILW) is disposal to a cementitious geological disposal facility (GDF). Under the alkaline (10.013.0) anoxic conditions expected within a GDF, cellulosic wastes will undergo chemical hydrolysis. The resulting cellulose degradation products (CDP) are dominated by alpha- and beta isosaccharinic acids (ISA), which present an organic carbon source that may enable subsequent microbial colonisation of a GDF. Microcosms established from neutral, near-surface sediments demonstrated complete ISA degradation under methanogenic conditions up to pH 10.0. Degradation decreased as pH increased, with beta-ISA fermentation more heavily influenced than alpha-ISA. This reduction in degradation rate was accompanied by a shift in microbial population away from organisms related to Clostridium sporosphaeroides to a more diverse Clostridial community. The increase in pH to 10.0 saw an increase in detection of Alcaligenes aquatilis and a dominance of hydrogenotrophic methanogens within the Archaeal population. Methane was generated up to pH 10.0 with acetate accumulation at higher pH values reflecting a reduced detection of acetoclastic methanogens. An increase in pH to 11.0 resulted in the accumulation of ISA, the absence of methanogenesis and the loss of biomass from the system. This study is the first to demonstrate methanogenesis from ISA by near surface microbial communities not previously exposed to these compounds up to and including pH 10.0. PMID- 26367007 TI - Segmentation of elemental EDS maps by means of multiple clustering combined with phase identification. AB - An imaging concept is proposed for the phase identification and segmentation of elemental map images from energy dispersive spectroscopy. The procedure starts with presegmentation using common clustering algorithms, continues with automated identification of the chemical compositions, followed by their screening by professional expertise. The ultimate phases are finally clustered by applying a minimum Euclidean distance classifier. The potential, performance and limitations of the approach are presented on energy dispersive spectroscopy maps acquired by a scanning electron microscope and conducted on samples produced from cement clinker, natural rock and hydrated cement mortar. Nevertheless, the technique is suitable for arbitrary types of materials and general devices for energy dispersive spectroscopy acquisition. It is an approach for extending common energy dispersive spectroscopy analysis by means of visual examination and ratio plots towards quantitative rating. PMID- 26367006 TI - Dissecting Leishmania infantum Energy Metabolism - A Systems Perspective. AB - Leishmania infantum, causative agent of visceral leishmaniasis in humans, illustrates a complex lifecycle pertaining to two extreme environments, namely, the gut of the sandfly vector and human macrophages. Leishmania is capable of dynamically adapting and tactically switching between these critically hostile situations. The possible metabolic routes ventured by the parasite to achieve this exceptional adaptation to its varying environments are still poorly understood. In this study, we present an extensively reconstructed energy metabolism network of Leishmania infantum as an attempt to identify certain strategic metabolic routes preferred by the parasite to optimize its survival in such dynamic environments. The reconstructed network consists of 142 genes encoding for enzymes performing 237 reactions distributed across five distinct model compartments. We annotated the subcellular locations of different enzymes and their reactions on the basis of strong literature evidence and sequence-based detection of cellular localization signal within a protein sequence. To explore the diverse features of parasite metabolism the metabolic network was implemented and analyzed as a constraint-based model. Using a systems-based approach, we also put forth an extensive set of lethal reaction knockouts; some of which were validated using published data on Leishmania species. Performing a robustness analysis, the model was rigorously validated and tested for the secretion of overflow metabolites specific to Leishmania under varying extracellular oxygen uptake rate. Further, the fate of important non-essential amino acids in L. infantum metabolism was investigated. Stage-specific scenarios of L. infantum energy metabolism were incorporated in the model and key metabolic differences were outlined. Analysis of the model revealed the essentiality of glucose uptake, succinate fermentation, glutamate biosynthesis and an active TCA cycle as driving forces for parasite energy metabolism and its optimal growth. Finally, through our in silico knockout analysis, we could identify possible therapeutic targets that provide experimentally testable hypotheses. PMID- 26367008 TI - Correction: CRISPR MultiTargeter: A Web Tool to Find Common and Unique CRISPR Single Guide RNA Targets in a Set of Similar Sequences. PMID- 26367009 TI - Clinical research for good clinical care. PMID- 26367010 TI - Sparse Spectro-Temporal Receptive Fields Based on Multi-Unit and High-Gamma Responses in Human Auditory Cortex. AB - Spectro-Temporal Receptive Fields (STRFs) were estimated from both multi-unit sorted clusters and high-gamma power responses in human auditory cortex. Intracranial electrophysiological recordings were used to measure responses to a random chord sequence of Gammatone stimuli. Traditional methods for estimating STRFs from single-unit recordings, such as spike-triggered-averages, tend to be noisy and are less robust to other response signals such as local field potentials. We present an extension to recently advanced methods for estimating STRFs from generalized linear models (GLM). A new variant of regression using regularization that penalizes non-zero coefficients is described, which results in a sparse solution. The frequency-time structure of the STRF tends toward grouping in different areas of frequency-time and we demonstrate that group sparsity-inducing penalties applied to GLM estimates of STRFs reduces the background noise while preserving the complex internal structure. The contribution of local spiking activity to the high-gamma power signal was factored out of the STRF using the GLM method, and this contribution was significant in 85 percent of the cases. Although the GLM methods have been used to estimate STRFs in animals, this study examines the detailed structure directly from auditory cortex in the awake human brain. We used this approach to identify an abrupt change in the best frequency of estimated STRFs along posteromedial-to anterolateral recording locations along the long axis of Heschl's gyrus. This change correlates well with a proposed transition from core to non-core auditory fields previously identified using the temporal response properties of Heschl's gyrus recordings elicited by click-train stimuli. PMID- 26367011 TI - Dissecting Germ Cell Metabolism through Network Modeling. AB - Metabolic pathways are increasingly postulated to be vital in programming cell fate, including stemness, differentiation, proliferation, and apoptosis. The commitment to meiosis is a critical fate decision for mammalian germ cells, and requires a metabolic derivative of vitamin A, retinoic acid (RA). Recent evidence showed that a pulse of RA is generated in the testis of male mice thereby triggering meiotic commitment. However, enzymes and reactions that regulate this RA pulse have yet to be identified. We developed a mouse germ cell-specific metabolic network with a curated vitamin A pathway. Using this network, we implemented flux balance analysis throughout the initial wave of spermatogenesis to elucidate important reactions and enzymes for the generation and degradation of RA. Our results indicate that primary RA sources in the germ cell include RA import from the extracellular region, release of RA from binding proteins, and metabolism of retinal to RA. Further, in silico knockouts of genes and reactions in the vitamin A pathway predict that deletion of Lipe, hormone-sensitive lipase, disrupts the RA pulse thereby causing spermatogenic defects. Examination of other metabolic pathways reveals that the citric acid cycle is the most active pathway. In addition, we discover that fatty acid synthesis/oxidation are the primary energy sources in the germ cell. In summary, this study predicts enzymes, reactions, and pathways important for germ cell commitment to meiosis. These findings enhance our understanding of the metabolic control of germ cell differentiation and will help guide future experiments to improve reproductive health. PMID- 26367012 TI - The Influence of Intersections on Fuel Consumption in Urban Arterial Road Traffic: A Single Vehicle Test in Harbin, China. AB - The calculating method for fuel consumption (FC) was put forward and calibrated and the characteristics of the fuel consumption on intersections were analyzed based on 18 groups of vehicular operating data which were acquired from the test experiment of a single vehicle along the urban arterial roads in Harbin, China. The results obtained show that 50.36% of the fuel consumption for the test vehicle was used at the area of intersections compared with 28.9% of the influencing distance and 68.5% of the running time; and 78.4% of them was burnt at the stages of acceleration and idling. Meanwhile, the type PMID- 26367013 TI - Functional conformer of c-Myb DNA-binding domain revealed by variable temperature studies. AB - The conformational fluctuation in the minimum DNA-binding domain of c-Myb, repeats 2 and 3 (R2R3), was studied under closely physiological conditions. A global unfolding transition, involving both the main chain and the side chains, was found to take place at the approximate temperature range 30-70 degrees C, with a transition temperature of approximately 50 degrees C. In addition, the observation of simultaneous shift change and broadening of NMR signals in both (1)H one-dimensional and (15)N/(1)H two-dimensional NMR spectra indicated the occurrence of locally fluctuating state at physiological temperature. In the wild type protein containing a cavity in R2, the local fluctuation of R2 is more prominent than that of R3, whereas it is suppressed in the cavity-filled mutant, V103L. This indicates that the cavity in R2 contributes significantly to the conformational instability and the transition into the locally fluctuating state. For the wild-type R2R3 protein, the more dynamic conformer is estimated to be present to some extent at 37 degrees C and is likely beneficial for its biological function: DNA-binding. This result is in agreement with the concept of an excited-state conformer that exists in equilibrium with the dominant ground state conformer and acts as the functional conformer of the protein. From the findings of the present study, it appears that the tandem repeats of two small domains with no disulfide bonds and with a destabilizing cavity function as the evolutionary strategy of the wide-type c-Myb DNA-binding domain to produce an appropriate fraction of the locally fluctuating state at 37 degrees C, which is more amenable to DNA-binding. Database: Chemical shifts and peak lists have been deposited in the Biological Magnetic Resonance Bank under entries 11584 and 11585. PMID- 26367014 TI - Influence of Genetic Ancestry on INDEL Markers of NFKbeta1, CASP8, PAR1, IL4 and CYP19A1 Genes in Leprosy Patients. AB - BACKGROUND: Leprosy is an insidious infectious disease caused by the obligate intracellular bacteria Mycobacterium leprae, and host genetic factors can modulate the immune response and generate distinct categories of leprosy susceptibility that are also influenced by genetic ancestry. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the possible effects of CYP19A1 [rs11575899], NFKbeta1 [rs28362491], IL1alpha [rs3783553], CASP8 [rs3834129], UGT1A1 [rs8175347], PAR1 [rs11267092], CYP2E1 [INDEL 96pb] and IL4 [rs79071878] genes in a group of 141 leprosy patients and 180 healthy individuals. The INDELs were typed by PCR Multiplex in ABI PRISM 3130 and analyzed with GeneMapper ID v3.2. The NFKbeta1, CASP8, PAR1 and IL4 INDELs were associated with leprosy susceptibility, while NFKbeta1, CASP8, PAR1 and CYP19A1 were associated with the MB (Multibacilary) clinical form of leprosy. CONCLUSIONS/SIGNIFICANCE: NFKbeta1 [rs28362491], CASP8 [rs3834129], PAR1 [rs11267092] and IL4 [rs79071878] genes are potential markers for susceptibility to leprosy development, while the INDELs in NFKbeta1, CASP8, PAR1 and CYP19A1 (rs11575899) are potential markers for the severe clinical form MB. Moreover, all of these markers are influenced by genetic ancestry, and European contribution increases the risk to leprosy development, in other hand an increase in African contribution generates protection against leprosy. PMID- 26367015 TI - Gold Nanoparticles Supported on a Layered Double Hydroxide as Efficient Catalysts for the One-Pot Synthesis of Flavones. AB - Flavones are a class of natural products with diverse biological activities and have frequently been synthesized by step-by-step procedures using stoichiometric amounts of reagents. Herein, a catalytic one-pot procedure for the synthesis of flavone and its derivatives is developed. In the presence of gold nanoparticles supported on a Mg-Al layered double hydroxide (Au/LDH), various kinds of flavones can be synthesized starting from 2'-hydroxyacetophenones and benzaldehydes (or benzyl alcohols). The present one-pot procedure consists of a sequence of several reactions, and Au/LDH can catalyze all these different types of reactions. The catalysis is shown to be truly heterogeneous, and Au/LDH can be readily recovered and reused. PMID- 26367016 TI - Functionalization of Metal-Organic Frameworks for Enhanced Stability under Humid Carbon Dioxide Capture Conditions. AB - Metal-organic frameworks (MOFs) have been highlighted recently as promising materials for CO2 capture. However, in practical CO2 capture processes, such as capture from flue gas or ambient air, the adsorption properties of MOFs tend to be harmed by the presence of moisture possibly because of the hydrophilic nature of the coordinatively unsaturated sites (CUSs) within their framework. In this work, the CUSs of the MOF framework are functionalized with amine-containing molecules to prevent structural degradation in a humid environment. Specifically, the framework of the magnesium dioxybenzenedicarboxylate (Mg/DOBDC) MOF was functionalized with ethylenediamine (ED) molecules to make the overall structure less hydrophilic. Structural analysis after exposure to high-temperature steam showed that the ED-functionalized Mg/DOBDC (ED-Mg/DOBDC) is more stable under humid conditions, than Mg/DOBDC, which underwent drastic structural changes. ED Mg/DOBDC recovered its CO2 adsorption capacity and initial adsorption rate quite well as opposed to the original Mg/DOBDC, which revealed a significant reduction in its capture capacity and kinetics. These results suggest that the amine functionalization of the CUSs is an effective way to enhance the structural stability of MOFs as well as their capture of humid CO2 . PMID- 26367017 TI - Temporal Associations Among Chronic PTSD Symptoms in U.S. Combat Veterans. AB - The present study examined fluctuation over time in symptoms of posttraumatic stress disorder (PTSD) among 34 combat veterans (28 with diagnosed PTSD, 6 with subclinical symptoms) assessed every 2 weeks for up to 2 years (range of assessments = 13-52). Temporal relationships were examined among four PTSD symptom clusters (reexperiencing, avoidance, emotional numbing, and hyperarousal) with particular attention to the influence of hyperarousal. Multilevel cross lagged random coefficients autoregression for intensive time series data analyses were used to model symptom fluctuation decades after combat experiences. As anticipated, hyperarousal predicted subsequent fluctuations in the 3 other PTSD symptom clusters (reexperiencing, avoidance, emotional numbing) at subsequent 2 week intervals (rs = .45, .36, and .40, respectively). Additionally, emotional numbing influenced later reexperiencing and avoidance, and reexperiencing influenced later hyperarousal (rs = .44, .40, and .34, respectively). These findings underscore the important influence of hyperarousal. Furthermore, results indicate a bidirectional relationship between hyperarousal and reexperiencing as well as a possible chaining of symptoms (hyperarousal -> emotional numbing -> reexperiencing -> hyperarousal) and establish potential internal, intrapersonal mechanisms for the maintenance of persistent PTSD symptoms. Results suggested that clinical interventions targeting hyperarousal and emotional numbing symptoms may hold promise for PTSD of long duration. PMID- 26367018 TI - CHRONOTYPE ASSOCIATIONS WITH DEPRESSION AND ANXIETY DISORDERS IN A LARGE COHORT STUDY. AB - BACKGROUND: The chronotype, being a morning or an evening type, can influence an individual's psychological health. Studies have shown a link between depressed mood and being an evening type; however, most studies have used symptom scales and not diagnostic criteria, and confounding factors such as sleep patterns and somatic health factors have often not been considered. This study aims to examine the association between chronotype and depressive (major depressive disorder (MDD), dysthymia) and anxiety (generalized anxiety disorder, panic disorder, agoraphobia, and social phobia) disorders diagnosed using clinical interviews, while taking into account relevant sociodemographic, clinical, somatic health, and sleep parameters. METHODS: Data from a large cohort, the Netherlands Study of Depression and Anxiety were used (n = 1,944), which included 676 currently depressed and/or anxious patients, 831 remitted patients, and 437 healthy controls. Chronotype was assessed using the Munich Chronotype Questionnaire. RESULTS: Our results showed that current depressive and/or anxiety disorders were associated with a late chronotype (beta = .10, P = .004) even when adjusting for sociodemographic, somatic health, and sleep-related factors (beta = .09, P = .03). When examining each type of disorder separately, MDD only, but not dysthymia or specific anxiety disorders, was associated with the late chronotype. The late chronotype also reported significant diurnal mood variation (worse mood in the morning). CONCLUSIONS: Our findings show a clear association between MDD and late chronotype (being an evening type), after controlling for a range of pertinent factors. A late chronotype is therefore associated with a current status of MDD and deserves the relevant clinical attention when considering treatments. PMID- 26367019 TI - Chemical Synthesis and Biological Activities of 20S,24S/R-Dihydroxyvitamin D3 Epimers and Their 1alpha-Hydroxyl Derivatives. AB - Bioactive vitamin D3 metabolites 20S,24S-dihydroxyvitamin D3 [20S,24S(OH)2D3] and 20S,24R-dihydroxyvitamin D3 [20S,24R(OH)2D3] were chemically synthesized and confirmed to be identical to their enzymatically generated counterparts. The absolute configurations at C24 and its influence on the kinetics of 1alpha hydroxylation by CYP27B1 were determined. Their corresponding 1alpha-hydroxyl derivatives were subsequently produced. Biological comparisons of these products showed different properties with respect to vitamin D3 receptor activation, anti inflammatory activity, and antiproliferative activity, with 1alpha,20S,24R(OH)2D3 being the most potent compound. PMID- 26367021 TI - Correction: Alternative Ultrasound Gel for a Sustainable Ultrasound Program: Application of Human Centered Design. PMID- 26367020 TI - Polyamide Nanogels from Generally Recognized as Safe Components and Their Toxicity in Mouse Preimplantation Embryos. AB - Safe delivery systems that can not only encapsulate hydrophobic drug molecules, but also release them in response to specific triggers are important in several therapeutic and biomedical applications. In this paper, we have designed a nanogel based on molecules that are generally recognized as safe (GRAS). We have shown that the resultant polymeric nanogels exhibit responsive molecular release and also show high in vitro cellular viability on HEK 293T, HeLa, MCF 7, and A549 cell lines. The toxicity of these nanogels was further evaluated with a highly sensitive assay using mouse preimplantation embryo development, where blastocysts were formed after 4 days of in vitro culture, and live pups were born when morulae/early blastocysts were transferred to the uteri of surrogate recipients. Our results indicate that these nanogels are nontoxic during mammalian development and do not alter normal growth or early embryo success rate. PMID- 26367022 TI - Transcatheter arterial embolisation in upper gastrointestinal bleeding in a sample of 29 patients in a gastrointestinal referral center in Germany. AB - OBJECTIVE: This is a retrospective analysis of interventional embolisation performed with catheter angiography in 29 patients with upper gastrointestinal bleeding in the setting of a secondary care hospital. PATIENTS, MATERIALS, AND METHODS: From April 2007 to February 2013, 29 patients with upper gastrointestinal bleeding underwent endovascular diagnostics and treatment. The diagnosis was established by endoscopy, computed tomography or clinically based on a significant decrease in hemoglobin. Transcatheter arterial embolisation was performed with coils, liquid embolic agents, and particles. The technical and clinical outcomes were assessed by postinterventional endoscopy, hemoglobin concentrations, number of necessary transfusions, or surgical interventions, as well as by post-interventional mortality within 28 days after the procedure. RESULTS: Selective angiographic embolisation in upper gastrointestinal bleeding was primarily successful technically and clinically in 22 of 29 patients. In 4/29 cases an angiographic reintervention was performed, which was successful in 3 cases. In 3 cases of primarily technically unsuccessful procedures reintervention was not attempted. No catheterisation-related complications were recorded. Peri interventional mortality was 31%, but only 2 of these patients died due to uncontrolled massive bleeding, whereas the lethal outcome in the other 7 patients was due to their underlying diseases. CONCLUSION: Transcatheter arterial embolisation is an effective and rapid method in the management of upper gastrointestinal bleeding. Radiological endovascular interventions may considerably contribute to reduced mortality in GI bleeding by avoiding a potential surgical procedure following unsuccessful endoscopic treatment. The study underlines the importance of the combination of interventional endoscopy with interventional radiology in secondary care hospitals for patient outcome in complex and complicated upper gastrointestinal bleeding situations. PMID- 26367023 TI - Extraesophageal symptoms of gastroesophageal reflux disease during pregnancy. AB - AIM: Typical symptoms of gastroesophageal reflux disease (GERD) are known to be frequent in pregnancy. The aim of this study was to gain a first estimation of the occurrence of extraesophageal symptoms in this context. METHODS: A prospective longitudinal study was performed on 166 pregnant women and in a control group of 285 women. The diagnosis of GERD was based on the Montreal classification using the reflux disease questionnaire (RDQ). Extraesophageal symptoms were recorded with a self-administered questionnaire. Typical GERD symptoms and extraesophageal GERD symptoms were recorded in each trimester of pregnancy. RESULTS: The prevalence of GERD during pregnancy was 16.9% in the first, 25.3% in the second and 51.2% in the third trimester. The prevalence of GERD in the control group was 6.3%. Asthma was reported by 3.5% of controls and by 6% of pregnant women during pregnancy. Chest pain occurred in 6% of the controls and in 1.8%, 2.4% and 2.4% during the trimesters of pregnancy, chronic cough was reported by 1.1% of controls and 1.2% of pregnant women. With the diagnosis of GERD the odds ratios and 95% confidence intervals for asthma, chronic cough and chest pain in the third trimester of pregnancy were as follows: 1.56 (0.58-4.22) for asthma, 0.91 (0.08-10.28) for chronic cough and 2.04 (0.49 8.46) for chest pain. CONCLUSION: GERD is very frequent during pregnancy with progressive incidence during the course of pregnancy. Extraesophageal symptoms of GERD have an unexpected low prevalence during pregnancy. PMID- 26367024 TI - Internal herniation due to an omphalomesenteric duct cyst in a 69-year-old man. AB - Previous abdominal surgery is the most common cause of mechanical small bowel obstruction. However, in patients with no history of abdominal surgery, the diagnosis and treatment of mechanical small bowel obstruction is difficult. A persistent omphalomesenteric duct remnant is a rare finding that typically presents in the pediatric population and is extremely rare in patients aged > 60 years. In the present report, we describe the case of an omphalomesenteric duct cyst causing small bowel obstruction in a 69-year-old man with no history of a surgical procedure. PMID- 26367025 TI - Recurrent pyogenic cholangitis as a differential diagnosis in biliary tract diseases. AB - Recurrent Pyogenic Cholangitis (RPC) or Primary Hepatolithiasis is a common disease of the biliary tract in Asia, whereas it is usually not seen in Europeans. With increasing global mobility, the disease will be encountered in Europe more frequently, too. It should therefore be considered as a differential diagnosis in patients from endemic countries with recurrent symptoms of cholestasis/cholangitis and bile duct dilations, strictures and hepatolithiasis. In this case report, we present the history of a 37-year old patient from Sri Lanka and describe typical aspects of RPC. The patient presented at our hospital with scleral jaundice and pruritus. In the past she had been treated for septic cholangitis. Diagnosis in our patient was made after laboratory tests, MRT/MRCP and ERC. She was treated interventionally by ERC and is now monitored on a regular basis. PMID- 26367026 TI - Lung disease and ulcerative colitis--mesalazine-induced bronchiolitis obliterans with organizing pneumonia or pulmonary manifestation of inflammatory bowel disease? AB - Ulcerative colitis can be associated with numerous extraintestinal organ manifestations. Pulmonary disease in inflammatory bowel disease (IBD) is supposed to be a rare entity and has to be distinguished from infectious complications and side-effects of medications used in the treatment of IBD. We present the case of a 20-year-old male patient with ulcerative colitis and a 4-week history of respiratory symptoms, malaise, fever and respiratory insufficiency under a medication with mesalazine. Computed tomography showed bilateral subpleural consolidations, bronchoscopy revealed signs of acute bronchitis. The diagnostic work-up ruled out an infectious cause. Under the tentative diagnosis of a mesalazine-induced bronchiolitis obliterans with organizing pneumonia (BOOP) the medication with mesalazine was withdrawn and the patient received a corticosteroid trial. The symptoms quickly improved and prednisone was tapered and stopped after 6 months. Unexpectedly, lung function after complete resolution of respiratory symptoms revealed a residual obstructive ventilatory defect that might be due to an asymptomatic pulmonary manifestation of ulcerative colitis. A review of the literature shows that pulmonary manifestations in IBD as well as pulmonary toxicity of mesalazine might not be as rare as expected and should be included as differential diagnoses in the work-up of respiratory symptoms in patients with IBD. A pragmatic therapeutic approach is reasonable in critically ill patients as it is not always easy to distinguish both entities. PMID- 26367027 TI - [Contrast-enhanced ultrasound for characterisation of focal liver lesions, practical advice]. AB - This review article reports on evidence-based and clinical aspects of contrast enhanced ultrasound of liver masses. The advanced possibilities of contrast enhanced ultrasound to detect and characterise liver tumors are described as well as limitations and pitfalls of the method. The choice of the ultrasound device and contrast agents as well as the qualifications of the examiners according to guidelines are discussed. PMID- 26367028 TI - [Regulation of T-cell trafficking in chronic inflammatory disease--far more complex!]. PMID- 26367029 TI - Dynamical Organization of Syntaxin-1A at the Presynaptic Active Zone. AB - Synaptic vesicle fusion is mediated by SNARE proteins forming in between synaptic vesicle (v-SNARE) and plasma membrane (t-SNARE), one of which is Syntaxin-1A. Although exocytosis mainly occurs at active zones, Syntaxin-1A appears to cover the entire neuronal membrane. By using STED super-resolution light microscopy and image analysis of Drosophila neuro-muscular junctions, we show that Syntaxin-1A clusters are more abundant and have an increased size at active zones. A computational particle-based model of syntaxin cluster formation and dynamics is developed. The model is parametrized to reproduce Syntaxin cluster-size distributions found by STED analysis, and successfully reproduces existing FRAP results. The model shows that the neuronal membrane is adjusted in a way to strike a balance between having most syntaxins stored in large clusters, while still keeping a mobile fraction of syntaxins free or in small clusters that can efficiently search the membrane or be traded between clusters. This balance is subtle and can be shifted toward almost no clustering and almost complete clustering by modifying the syntaxin interaction energy on the order of only 1 kBT. This capability appears to be exploited at active zones. The larger active zone syntaxin clusters are more stable and provide regions of high docking and fusion capability, whereas the smaller clusters outside may serve as flexible reserve pool or sites of spontaneous ectopic release. PMID- 26367031 TI - Anharmonicity Effects in IR Spectra of [Re(X)(CO)3(alpha-diimine)] (alpha-diimine = 2,2'-bipyridine or pyridylimidazo[1,5-a]pyridine; X = Cl or NCS) Complexes in Ground and Excited Electronic States. AB - Infrared spectra of [Re(X)(CO)(3)(alpha-diimine)] (alpha-diimine = 2,2' bipyridine, X = Cl, NCS, or pyridylimidazo[1,5-a]pyridine, X = Cl) in the ground and the lowest triplet electronic states were calculated by a global hybrid density functional going beyond the harmonic level by means of second-order vibrational perturbation theory (VPT2) and including bulk solvent effects by the polarizable continuum model (PCM). The full-dimensionality (FD) VPT2 is compared with the reduced-dimensionality (RD) model, where only selected vibrational modes are calculated anharmonically. The simulated difference IR spectra (excited state minus ground state) in the nu(CO) region closely match experimental time-resolved infrared (TRIR) spectra. Very good agreement was also obtained for ground-state spectra in the fingerprint region. In comparison with the harmonic simulated spectra, the calculated anharmonic frequencies are closer to experimental values and do not require scaling when the B3LYP functional is used. Several spectral features due to combination bands have been identified by VPT2 simulations in the nu(CO) spectral region, which are of importance for a correct interpretation of TRIR experiments. PMID- 26367030 TI - Antibodies to S. aureus LukS-PV Attenuated Subunit Vaccine Neutralize a Broad Spectrum of Canonical and Non-Canonical Bicomponent Leukotoxin Pairs. AB - S. aureus vaccine development has proven particularly difficult. The conventional approach to achieve sterile immunity through opsonophagocytic killing has been largely unsuccessful. S. aureus is highly toxigenic and a great body of evidence suggests that a successful future vaccine for this organism should target extracellular toxins which are responsible for host tissue destruction and immunosuppression. Major staphylococcal toxins are alpha toxin (a single subunit hemolysin) along with a group of bicomponent pore-forming toxins (BCPFT), namely Panton-Valentine leukocidin (PVL), gamma hemolysins (HlgCB and AB), LukAB and LukED. In our previous report, an attenuated mutant of LukS-PV (PVL- S subunit) named as "LukS-mut9" elicited high immunogenic response as well as provided a significant protection in a mouse sepsis model. Recent discovery of PVL receptors shows that mice lack receptors for this toxin, thus the reported protection of mice with the PVL vaccine may relate to cross protective responses against other homologous toxins. This manuscript addresses this issue by demonstrating that polyclonal antibody generated by LukS-mut9 can neutralize other canonical and non canonical leukotoxin pairs. In this report, we also demonstrated that several potent toxins can be created by non-canonical pairing of subunits. Out of 5 pairs of canonical and 8 pairs of non-canonical toxins tested, anti-LukS-mut9 polyclonal antibodies neutralized all except for LukAB. We also studied the potential hemolytic activities of canonical and noncanonical pairs among biocomponent toxins and discovered that a novel non-canonical pair consisting of HlgA and LukD is a highly toxic combination. This pair can lyse RBC from different species including human blood far better than alpha hemolysin. Moreover, to follow-up our last report, we explored the correlation between the levels of pre-existing antibodies to new sets of leukotoxins subunits and clinical outcomes in adult patients with S. aureus bacteremia. We found that there is an inversed correlation between the antibody titer to sepsis for leukotoxins LukS-mut9, LukF-PV, HlgC, LukE and LukAB, suggesting the risk of sepsis was significantly lower in the patients with higher antibody titer against those toxins. PMID- 26367033 TI - General scale-dependent anisotropic turbulence and its impact on free space optical communication system performance. AB - We generalize a recently introduced model for nonclassic turbulent spatial power spectrum involving anisotropy along two mutually orthogonal axes transverse to the direction of beam propagation by including two scale-dependent weighting factors for these directions. Such a turbulent model may be pertinent to atmospheric fluctuations in the refractive index in stratified regions well above the boundary layer and employed for air-air communication channels. When restricting ourselves to an unpolarized, coherent Gaussian beam and a weak turbulence regime, we examine the effects of such a turbulence type on the OOK FSO link performance by including the results on scintillation flux, probability of fade, SNR, and BERs. PMID- 26367032 TI - Challenging Postural Tasks Increase Asymmetry in Patients with Parkinson's Disease. AB - The unilateral predominance of Parkinson's disease (PD) symptoms suggests that balance control could be asymmetrical during static tasks. Although studies have shown that balance control asymmetries exist in patients with PD, these analyses were performed using only simple bipedal standing tasks. Challenging postural tasks, such as unipedal or tandem standing, could exacerbate balance control asymmetries. To address this, we studied the impact of challenging standing tasks on postural control asymmetry in patients with PD. Twenty patients with PD and twenty neurologically healthy individuals (control group) participated in this study. Participants performed three 30s trials for each postural task: bipedal, tandem adapted and unipedal standing. The center of pressure parameter was calculated for both limbs in each of these conditions, and the asymmetry between limbs was assessed using the symmetric index. A significant effect of condition was observed, with unipedal standing and tandem standing showing greater asymmetry than bipedal standing for the mediolateral root mean square (RMS) and area of sway parameters, respectively. In addition, a group*condition interaction indicated that, only for patients with PD, the unipedal condition showed greater asymmetry in the mediolateral RMS and area of sway than the bipedal condition and the tandem condition showed greater asymmetry in the area of sway than the bipedal condition. Patients with PD exhibited greater asymmetry while performing tasks requiring postural control when compared to neurologically healthy individuals, especially for challenging tasks such as tandem and unipedal standing. PMID- 26367034 TI - Optical sharper focusing in an anisotropic crystal. AB - Optical super-resolution technique through tight focusing is a widely used technique to image material samples with anisotropic optical properties. The knowledge of the field distribution of a tightly focused beam in anisotropic media is both scientifically interesting and technologically important. In this paper, the optical properties of a uniaxial crystal with the optic axis perpendicular to the interface under a tight focusing configuration are studied with rigorous theoretical and numerical analysis. The significant effect of the Poynting vector on the focal position introduces an obvious displacement of the focal spot formed by the extraordinary waves (e-ray). Moreover, a sharper focus with a lateral size of 0.22lambda is obtained as a result of the effective separation of the ordinary waves (o-ray) and the e-ray. It provides a new tool to fabricate optical structures with higher resolutions than that in an isotropic medium through the far-field method. PMID- 26367035 TI - Mimicking photon propagation through two-dimensional waveguide array by a one dimensional waveguide array. AB - Photon propagation through 1D and 2D waveguide arrays has been explored for various applications in the fields of quantum optics and quantum information. In this paper, we show that an appropriately designed 1D waveguide array can mimic the photon propagation through a 2D array. This alternative design is enticing since fabrication of 1D arrays is relatively less burdensome than 2D arrays. PMID- 26367036 TI - Polarization properties of a broadband multi-moded concentrator. AB - We present the design and performance of a non-imaging concentrator for use in broadband polarimetry at millimeter through submillimeter wavelengths. A rectangular geometry preserves the input polarization state as the concentrator couples f/2 incident optics to a 2pi sr detector. Measurements of the co-polar and cross-polar beams in both the few-mode and highly over-moded limits agree with a simple model based on mode truncation. The measured co-polar beam pattern is nearly independent of frequency in both linear polarizations. The cross-polar beam pattern is dominated by a uniform term corresponding to polarization efficiency of 94%. After correcting for efficiency, the remaining cross-polar response is -18 dB. PMID- 26367037 TI - Superpositions of asymmetrical Bessel beams. AB - We considered nonparaxial asymmetrical Bessel modes of the first and second types, which differ from a conventional symmetrical Bessel mode by a real-valued shift along one Cartesian coordinate and an imaginary shift along another (both shifts are equal in modulus). The first- and second-type Bessel modes differ only in signs of the shift and, therefore, have different orbital angular momentum (OAM) (integer or fractional). Addition and subtraction of complex amplitudes of two identical asymmetrical Bessel modes of the first and second type lead to light beams with the same integer OAM equal to the topological charge n of the original mode, but with different transverse intensity distributions, which depend on the shift magnitude. This proposed method allows controlling of the OAM of the beam with simultaneous changing of its shape, i.e., for matching with the object being trapped. PMID- 26367038 TI - Angular scattering of light by a homogeneous spherical particle in a zeroth-order Bessel beam and its relationship to plane wave scattering. AB - The angular scattering of light from a homogeneous spherical particle in a zeroth order Bessel beam is calculated using a generalized Lorenz-Mie theory. We investigate the dependence of the angular scattering on the semi-apex angle of the Bessel beam and discuss the major features of the resulting scattering plots. We also compare Bessel beam scattering to plane wave scattering and provide criterion for when the difference between the two cases can be considered negligible. Finally, we discuss a method for characterizing spherical particles using angular light scattering. This work is useful to researchers who are interested in characterizing particles trapped in optical beams using angular dependent light scattering measurements. PMID- 26367039 TI - Performance analysis of compressive ghost imaging based on different signal reconstruction techniques. AB - We present different signal reconstruction techniques for implementation of compressive ghost imaging (CGI). The different techniques are validated on the data collected from ghost imaging with the pseudothermal light experimental system. Experiment results show that the technique based on total variance minimization gives high-quality reconstruction of the imaging object with less time consumption. The different performances among these reconstruction techniques and their parameter settings are also analyzed. The conclusion thus offers valuable information to promote the implementation of CGI in real applications. PMID- 26367040 TI - Estimation of bispectral Donaldson matrices of fluorescent objects by using two illuminant projections. AB - This paper proposes a method for estimating the bispectral Donaldson matrices of fluorescent objects by using only two illuminant projections with continuous spectral power distributions. The Donaldson matrix represents the spectral radiance factor consisting of the sum of two components: a reflected radiance factor and a luminescent radiance factor. First, we describe the spectral characteristics of the observed matrix and model the matrix so that the luminescent radiance factor is separable into the emission and excitation wavelength components. We make no assumption as to the spectral shapes of any components, but derive a physical model that is useful for predicting the excitation spectral component from the reflected radiance component. An algorithm is developed to estimate the entire elements of the Donaldson matrix based on only two sets of spectral sensor outputs under two different illuminants. We suggest that the difference between the observed reflected radiance factors under the two different illuminants is not caused by the reflected radiance component, but only the luminescent radiance component. The algorithm is a sequential estimation of three radiance components of luminescent excitation, luminescent emission, and reflection. The feasibility of the proposed method is confirmed in experiments using a variety of fluorescent samples. The estimation accuracy is evaluated numerically in root-mean squared error and the color difference under the assumption of a viewing illuminant. An optimal selection of the illuminant pair is shown based on a simulation experiment using blackbody radiators with different color temperatures. PMID- 26367041 TI - Spectra restoration of a transmissive periodic structure in near-field diffraction (Talbot spectra). AB - The free-space near-field diffraction of a transmissive periodic structure is studied with Fresnel-Kirchhoff diffraction formula. A new effect named Talbot spectra is proposed theoretically from the results, showing that under some conditions the spectra of an incident coherent polychromatic light can be completely restored after the diffraction. It can be contrasted with its monochromatic counterpart, Talbot images, which rebuild the images of a periodic structure at specific places in the near field. Taking a sinusoidal amplitude grating as an example for illustrating the idea, the general conditions and specific locations to find the restored spectra are obtained. The spectral switches involved are also presented. PMID- 26367042 TI - Evaluation criterion of thermal light ghost imaging based on the receiver operating characteristic analysis. AB - The performances of different thermal ghost imaging (GI) algorithms are compared in an experiment of computational GI using a digital micromirror device. Here we present a rather different evaluation criterion named receiver operating characteristic (ROC) analysis that serves as the performance of merit for the quantitative comparison. A ROC curve is created by plotting the true positive rate against the false positive rate at various threshold settings. Both theoretical analysis and experimental results demonstrate that the ROC curve and the area under the curve are better and more intuitive indicators of the performance of the GI, compared with conventional evaluation methods. Additionally, for examining gray-scale objects, the calculation of the volume under the ROC surface is analyzed and serves as a performance metric. Our scheme should attract general interest and open exciting prospects for ROC analysis in thermal GI. PMID- 26367043 TI - Isotropic inverse-problem approach for two-dimensional phase unwrapping. AB - We propose a new technique for two-dimensional phase unwrapping. The unwrapped phase is found as the solution of an inverse problem that consists in the minimization of an energy functional. The latter includes a weighted data fidelity term that favors sparsity in the error between the true and wrapped phase differences, as well as a regularizer based on higher-order total variation. One desirable feature of our method is its rotation invariance, which allows it to unwrap a much larger class of images compared to the state of the art. We demonstrate the effectiveness of our method through several experiments on simulated and real data obtained through the tomographic phase microscope. The proposed method can enhance the applicability and outreach of techniques that rely on quantitative phase evaluation. PMID- 26367044 TI - Electromagnetic scattering and absorption by randomly oriented fibers. AB - In this paper, we numerically calculate the extinction, scattering, absorption, and radar cross sections for a randomly oriented finite conducting fiber. Calculations in the long (centimeter) and short (infrared) wavelengths are presented and compared with the fixed orientation value when the incident electric field is aligned along the fiber length. The calculations presented in this paper are necessary for the parametrization of fibers to play the role of efficient obscurant and anti-radio frequency interference. PMID- 26367045 TI - Easy approach to assembling a biomimetic color film with tunable structural colors. AB - The self-assembly of silica microspheres into a close-packed array is a simple method of fabricating three-dimensional photonic crystal structural color films. However, the color is very dull because of the interferences of scattering and background light. In this study, we added a small quantity of surface-modified carbon black (CB) to the system of colloidal silica in n-propanol. The use of n propanol as a dispersant is beneficial to the rapid development of photonic crystal films during the process of dip-coating. The doping of CB into silica microspheres can absorb background and scattering light, resulting in vivid structural colors. PMID- 26367046 TI - Free space optical communication using beam parameters with translational and transverse rotational invariance. AB - Two natural requirements on a measurable quantity possessed by a paraxially propagating light-field to be suitable for free space optical communication are invariance under free space propagation and invariance under transverse plane rotation. While the former invariance ensures that the measurable quantity is robust while signalling through free space, the latter invariance ensures that a detector measuring the quantity can be oriented at any angle in the transverse plane, and a measurement by the detector yields the same value for the quantity irrespective of the transverse angle, thus avoiding alignment issues. The variance matrix of a paraxially propagating light-field is analyzed from the perspective of the aforementioned invariances. That the "charge" of a paraxial light-field, which is contained in the variance matrix, and which has been previously well studied for its suitability toward free space optical communication, possesses these two invariance properties, emerges naturally in the analysis. Seven functionally independent quantities other than charge, which are derived from the variance matrix, and which share these invariances, are presented and studied for their suitability toward signalling through turbulent atmosphere using the low-order Hermite-Gaussian modes. It is found that the spot size of a Gaussian light-field can be effectively used as a switch, to communicate through short distances in a turbulent atmosphere. PMID- 26367047 TI - Compositional prior information in computed infrared spectroscopic imaging. AB - Compositional prior information is used to bridge a gap in the theory between optical coherence tomography (OCT), which provides high-resolution structural images by neglecting spectral variation, and imaging spectroscopy, which provides only spectral information without significant regard to structure. A constraint is proposed in which it is assumed that a sample is composed of N distinct materials with known spectra, allowing the structural and spectral composition of the sample to be determined with a number of measurements on the order of N. We present a forward model for a sample with heterogeneities along the optical axis and show through simulation that the N-species constraint allows unambiguous inversion of Fourier transform interferometric data within the spatial frequency passband of the optical system. We then explore the stability and limitations of this model and extend it to a general 3D heterogeneous sample. PMID- 26367048 TI - Phases of Talbot patterns in angular self-imaging. AB - The original Talbot (self-imaging) effect is observed in the vicinity of a grating of slits shined with a plane wave, and results in periodic images of the initial diffraction pattern (integer Talbot effect) and the appearance of images with a periodicity reduced by an integer factor (fractional Talbot effect). Most of the studies on Talbot effect so far have focused on the distribution of the intensity of the diffracted light. However, the phases of the Talbot images, obtained in both the integer and fractional self-imaging cases, can be calculated in a closed form and display interesting auto-correlation properties. This paper reports what is, to the best of our knowledge, the first experimental investigation of the phases of Talbot images beyond the integer self-imaging case. We address the problem of experimental measurement of the phases of the Talbot images in the equivalent frame of the angular Talbot effect, a recently reported manifestation of the Talbot effect in the far field. The phases of the Talbot images are measured by far-field holography, and the obtained results are in excellent agreement with theoretical calculations. They also suggest the possibility of using the scheme for a precise "fractional ruler" aimed at distances' measurements. PMID- 26367049 TI - Revival and splitting of a Gaussian beam in gradient index media. AB - The short range revival of an arbitrary monochromatic optical field, which propagates in a quadratic GRIN rod, is a well-known effect that is established assuming the first-order approximation of the propagation operator. We discuss the revival and multiple splitting of an off-axis Gaussian beam propagating to relatively long distances in a quadratic GRIN medium. These effects are obtained assuming the second-order approximation of the propagation operator in this medium. PMID- 26367050 TI - Derivation of various transfer functions of ideal or aberrated imaging systems from the three-dimensional transfer function. AB - The three-dimensional frequency transfer function for optical imaging systems was introduced by Frieden in the 1960s. The analysis of this function and its partly back-transformed functions (two-dimensional and one-dimensional optical transfer functions) in the case of an ideal or aberrated imaging system has received relatively little attention in the literature. Regarding ideal imaging systems with an incoherently illuminated object volume, we present analytic expressions for the classical two-dimensional x-y-transfer function in a defocused plane, for the axial z-transfer function in the presence of defocusing and for the x-z transfer function in the presence of a lateral shift deltay with respect to the imaged pattern in the x-z-plane. For an aberrated imaging system we use the common expansion of the aberrated pupil function with the aid of Zernike polynomials. It is shown that the line integral appearing in Frieden's three dimensional transfer function can be evaluated for aberrated systems using a relationship established first by Cormack between the line integral of a Zernike polynomial over a full chord of the unit disk and a Chebyshev polynomial of the second kind. Some new developments in the theory of Zernike polynomials from the last decade allow us to present explicit expressions for the line integral in the case of a weakly aberrated imaging system. We outline a similar, but more complicated, analytic scheme for the case of severely aberrated systems. PMID- 26367051 TI - Modal-based phase retrieval for adaptive optics. AB - We consider using phase retrieval (PR) to correct phase aberrations in an optical system. Three measurements of the point-spread function (PSF) are collected to estimate an aberration. For each measurement, a different defocus aberration is applied with a deformable mirror (DM). Once the aberration is estimated using a PR algorithm, we apply the aberration correction with the DM, and measure the residual aberration using a Shack-Hartmann wavefront sensor. The extended Nijboer Zernike theory is used for modelling the PSF. The PR problem is solved using both an algorithm called PhaseLift, which is based on matrix rank minimization, and another algorithm based on alternating projections. For comparison, we include the results achieved using a classical PR algorithm, which is based on alternating projections and uses the fast Fourier transform. PMID- 26367052 TI - Low-quality fingerprint recognition using a limited ellipse-band-based matching method. AB - Current fingerprint recognition technologies are based mostly on the minutia algorithms, which cannot recognize fingerprint images in low-quality conditions. This paper proposes a novel recognition algorithm using a limited ellipse-band based matching method. It uses the Fourier-Mellin transformation method to improve the limitation of the original algorithm, which cannot resist rotation changes. Furthermore, an ellipse band on the frequency amplitude is used to suppress noise that is introduced by the high-frequency parts of images. Finally, the recognition result is obtained by considering both the contrast and position correlation peaks. The experimental results show that the proposed algorithm can increase the recognition accuracy, particularly of images in low-quality conditions. PMID- 26367053 TI - Difference between the Brewster angle and angle of minimum reflectance for incident unpolarized or circularly polarized light at interfaces between transparent media. AB - For reflection at interfaces between transparent optically isotropic media, the difference between the Brewster angle phiB of zero reflectance for incident p polarized light and the angle phiu min of minimum reflectance for incident unpolarized or circularly polarized light is considered as function of the relative refractive n in external and internal reflection. We determine the following. (i) phiu min < phiB for all values of n. (ii) In external reflection (n > 1), the maximum difference (phiB - phiu min)max = 75 degrees at n = 2 + ?3. (iii) In internal reflection and 0 < n <= 2 - ?3, (phiB - phiu min)max = 15 degrees at n = 2 - ?3; for 2 - ?3 < n < 1, phiu min = 0, and (phiB - phiu min)max = 45 degrees as n -> 1. (iv) For 2 - ?3 <= n <= 2 + ?3, the intensity reflectance R0 at normal incidence is in the range 0 <= R0 <= 1/3, phiu min = 0, and phiB - phiu min = phiB. (v) For internal reflection and 0 < n < 2 - ?3, phiu min exhibits an unexpected maximum (= 12.30 degrees ) at n = 0.24265. Finally, (vi) for 1/3 <= R0 < 1, Ru min at phiu min is limited to the range 1/3 <= Ru min < 1/2. PMID- 26367054 TI - Electromagnetic wave transmission through a subwavelength nano-hole in a two dimensional plasmonic layer. AB - An integral equation is formulated to describe electromagnetic wave transmission through a subwavelength nano-hole in a thin plasmonic sheet in terms of the dyadic Green's function for the associated Helmholtz problem. Taking the subwavelength radius of the nano-hole to be the smallest length of the system, we have obtained an exact solution of the integral equation for the dyadic Green's function analytically and in closed form. This dyadic Green's function is then employed in the numerical analysis of electromagnetic wave transmission through the nano-hole for normal incidence of the incoming wave train. The electromagnetic transmission involves two distinct contributions; one emanates from the nano-hole, and the other is directly transmitted through the thin plasmonic layer itself (which would not occur in the case of a perfect metal screen). The transmitted radiation exhibits interference fringes in the vicinity of the nano-hole, and they tend to flatten as a function of increasing lateral separation from the hole, reaching the uniform value of transmission through the sheet alone at large separations. PMID- 26367055 TI - Analysis of temporal power spectra for optical waves propagating through weak anisotropic non-Kolmogorov turbulence. AB - Analytic expressions for the temporal power spectra of irradiance fluctuations and angle of arrival (AOA) fluctuations are derived for optical waves propagating through weak anisotropic non-Kolmogorov atmospheric turbulence. In the derivation, the anisotropic non-Kolmogorov spectrum is adopted, which adopts the assumption of circular symmetry in the orthogonal plane throughout the path and the same degree of anisotropy along the propagation direction for all the turbulence cells. The final expressions consider simultaneously the anisotropic factor and general spectral power law values. When the anisotropic factor equals one (corresponding to the isotropic turbulence), the derived temporal power spectral models have good consistency with the known results for the isotropic turbulence. Numerical calculations show that the increased anisotropic factor alleviates the atmospheric turbulence's influence on the final expressions. PMID- 26367056 TI - Creation of a 50,000lambda long needle-like field with 0.36lambda width: comment. AB - In a recent paper, a method for the generation of a long, narrow needle of light was proposed [J. Opt. Soc. Am. A31, 500 (2014)10.1364/JOSAA.31.000500JOAOD61084 7529]. The authors missed fundamental aspects of the mathematical physics of cylindrical electromagnetic waves described by Bessel functions that are essential to obtain the proposed needle. We provide formal arguments showing that a different initial condition is the proper one for the intended purpose. Based on their proposed method we bring to attention the validity of Huygens' principle for cylindrical waves. Also, we extend their analysis in order to have a component of longitudinal energy flow that is needed for most of the applications they suggest. We quantitatively show that a minor modification produces this component with practically negligible increase of the needle width. PMID- 26367057 TI - Creation of a 50,000lambda long needle-like field with 0.36lambda width: reply. AB - This is the reply to the comment by Chavez-Cerda and Pu [J. Opt. Soc. Am. A32, 1209 (2015)JOAOD61084-752910.1364/JOSAA.32.001209] on our recent work about the 50,000lambda long needle-like field [J. Opt. Soc. Am. A31, 500 (2014)JOAOD60740 323210.1364/JOSAA.31.000500]. First, they employed an incorrect boundary condition as the fundament of their argument. In fact, it is not the electric field but its tangential component that must be zero at the surface of the perfect metal. Our result is completely consistent with the correct boundary condition. Second, a constant phase factor in the incident radially polarized beam, exp(jpi/4), for instance, has no influence on the result. Accordingly, our initial condition is proper. PMID- 26367058 TI - IgG Conformer's Binding to Amyloidogenic Aggregates. AB - Amyloid-reactive IgGs isolated from pooled blood of normal individuals (pAbs) have demonstrated clinical utility for amyloid diseases by in vivo targeting and clearing amyloidogenic proteins and peptides. We now report the following three novel findings on pAb conformer's binding to amyloidogenic aggregates: 1) pAb aggregates have greater activity than monomers (HMW species > dimers > monomers), 2) pAbs interactions with amyloidogenic aggregates at least partially involves unconventional (non-CDR) interactions of F(ab) regions, and 3) pAb's activity can be easily modulated by trace aggregates generated during sample processing. Specifically, we show that HMW aggregates and dimeric pAbs present in commercial preparations of pAbs, intravenous immunoglobulin (IVIg), had up to ~200- and ~7 fold stronger binding to aggregates of Abeta and transthyretin (TTR) than the monomeric antibody. Notably, HMW aggregates were primarily responsible for the enhanced anti-amyloid activities of Abeta- and Cibacron blue-isolated IVIg IgGs. Human pAb conformer's binding to amyloidogenic aggregates was retained in normal human sera, and mimicked by murine pAbs isolated from normal pooled plasmas. An unconventional (non-CDR) component to pAb's activity was indicated from control human mAbs, generated against non-amyloid targets, binding to aggregated Abeta and TTR. Similar to pAbs, HMW and dimeric mAb conformers bound stronger than their monomeric forms to amyloidogenic aggregates. However, mAbs had lower maximum binding signals, indicating that pAbs were required to saturate a diverse collection of binding sites. Taken together, our findings strongly support further investigations on the physiological function and clinical utility of the inherent anti-amyloid activities of monomeric but not aggregated IgGs. PMID- 26367060 TI - The efficacy of trivalent cyclic hexapeptides to induce lipid clustering in PG/PE membranes correlates with their antimicrobial activity. AB - Various models have been proposed for the sequence of events occurring after binding of specific antimicrobial peptides to lipid membranes. The lipid clustering model arose by the finding that antimicrobial peptides can induce a segregation of certain negatively charged lipids in lipid model membranes. Anionic lipid segregation by cationic peptides is initially an effect of charge interaction where the ratio of peptide and lipid charges is thought to be the decisive parameter in the peptide induced lipid demixing. However, the sequence of events following this initial lipid clustering is more complex and can lead to deactivation of membrane proteins involved in cell division or perturbation of lipid reorganization essential for cell division. In this study we used DSC and ITC techniques to investigate the effect of binding different cyclic hexapeptides with varying antimicrobial efficacy, to phosphatidylglycerol (PG)/phosphatidylethanolamine (PE) lipid membranes and their ability to induce lipid segregation in these mixtures. We found that these cyclic hexapeptides consisting of three charged and three aromatic amino acids showed indeed different abilities to induce lipid demixing depending on their amino acid composition and their sequence. The results clearly showed that the cationic amino acids are essential for electrostatic binding but that the three hydrophobic amino acids in the peptides and their position in the sequence also contribute to binding affinity and to the extent of induction of lipid clustering. The efficacy of these different hexapeptides to induce PG clusters in PG/PE membranes was found to be correlated with their antimicrobial activity. PMID- 26367059 TI - Magnetic Resonance Imaging of Mitochondrial Dysfunction and Metabolic Activity, Accompanied by Overproduction of Superoxide. AB - This study shows that a mitochondria-penetrating nitroxide probe (mito-TEMPO) allows detection of superoxide and visualization of mitochondrial dysfunction in living cells due to the effect of T1 shortening in MRI. Mitochondrial dysfunction was induced by treatment of cells with rotenone and 2-methoxyestradiol (2 ME/Rot). The MRI measurements were performed on 7T MRI. The 2-ME/Rot-treated cells were characterized by overproduction of superoxide, which was confirmed by a conventional dihydroethidium test. In the presence of mito-TEMPO, the intensity of MRI signal in 2-ME/Rot-treated cells was ~30-40% higher, in comparison with that in untreated cells or culture media. In model (cell-free) systems, we observed that superoxide, but not hydrogen peroxide, increased the intensity of T1-weighted MRI signal of mito-TEMPO. Moreover, the superoxide restores the T1 weighted MRI contrast of mito-TEMPOH, a noncontrast (diamagnetic) analogue of mito-TEMPO. This was also confirmed by using EPR spectroscopy. The results demonstrate that superoxide radical is involved in the enhancement of T1-weighted MRI contrast in living cells, in the absence and presence of mito-TEMPO. This report gives a direction for discovering new opportunities for functional MRI, for detection of metabolic activity, accompanied by overproduction of superoxide, as well as by disturbance of the balance between superoxide and hydrogen peroxide, a very important approach to clarify the fine molecular mechanisms in the regulation of many pathologies. The visualization of mitochondrial activity in real-time can be crucial to clarify the molecular mechanism of the functional MRI in its commonly accepted definition, as a method for detection of neurovascular coupling. PMID- 26367061 TI - Hb40-61a: Novel analogues help expanding the knowledge on chemistry, properties and candidacidal action of this bovine alpha-hemoglobin-derived peptide. AB - This study expands the knowledge on chemical synthesis and properties of Hb40-61a as well as provides results of the first steps given towards knowing how it kills Candida cells. For the first time, this peptide, its all-D analogue (D-Hb40-61a) and its fluorescently labeled analogue (FAM-Hb40-61a) were successfully assembled on resin at 60 degrees C using conventional heating in all steps. Purified and characterized, these peptides exhibited very low toxicity on human erythrocytes. Hb40-61a and D-Hb40-61a were equally active against Candida strains, ruling out sterically specific interactions on their working mechanism. Cell permeabilization assays confirmed progressive damage of the yeast plasma membrane with increasing concentrations of Hb40-61a. While experiment using the fluorescent probe DiBAC4(5) revealed that this synthetic hemocidin alters the yeast plasma membrane potential, test employing DPH indicated that Hb40-61a might affect its dynamics. Exposure of the yeast cells to FAM-Hb40-61a showed that the peptide accumulates in the cell membrane at the 1/2 MIC, but stains about 97% of the cells at the MIC. Such effect is salt-dependent and partially energy dependent. These new findings indicate that the central target of Hb40-61a in Candida cells is the plasma membrane and that this synthetic hemocidin should be considered as a potential candidacidal for topic uses. PMID- 26367062 TI - Do speakers have access to a mental syllabary? ERP comparison of high frequency and novel syllable production. AB - The transformation of an abstract phonological code into articulation has been hypothesized to involve the retrieval of stored syllable-sized motor plans. Accordingly, gestural scores for frequently used syllables are retrieved from memory whereas gestural scores for novel and possibly low frequency syllables are assembled on-line. The present study was designed to test this hypothesis. Participants produced disyllabic pseudowords with high frequency, low frequency and non-existent (novel) initial syllables. Behavioral results revealed slower production latencies for novel than for high frequency syllables. Event-related potentials diverged in waveform amplitudes and global topographic patterns between high frequency and low frequency/novel syllables around 170 ms before the onset of articulation. These differences indicate the recruitment of different brain networks during the production of frequent and infrequent/novel syllables, in line with the hypothesis that speakers store syllabic-sized motor programs for frequent syllables and assemble these motor plans on-line for low frequency and novel syllables. PMID- 26367063 TI - Enterovirus D68 and Panton-Valentine Leukocidin-Positive Staphylococcus aureus Respiratory Coinfection with Fatal Outcome. AB - A previously healthy 10-year-old girl with a 2-day history of upper respiratory illness and fever rapidly developed respiratory failure and sepsis with leukopenia, and expired despite attempts at resuscitation. Postmortem examination revealed bilateral necrotizing pneumonia and evidence of disseminated intravascular coagulation. Nasopharyngeal swabs and lung tissue submitted to the Centers for Disease Control and Prevention (CDC) were positive for Enterovirus D68 (EV-D68). Blood and lung cultures were positive for methicillin-resistant Staphylococcus aureus (MRSA). The isolates were submitted to the CDC and were found to be positive for the toxin Panton-Valentine leukocidin. We describe a fatality related to invasive toxin-mediated MRSA associated with EV-D68 coinfection, along with the clinical, laboratory, and autopsy findings, which provided important clues, prompting further investigation at the CDC to arrive at the correct diagnosis. PMID- 26367064 TI - Hot environments decrease exercise capacity and elevate multiple neurotransmitters. AB - AIMS: This study aimed to test the hypothesis that different neurotransmitters and hormones are presented at exercise fatigue in hot temperatures with differing relative humidities (RH). MAIN METHODS: Eight trained male athletes performed a graded maximum oxygen consumption (VO2max) test in five different environmental conditions, namely, 21 degrees C/20% RH (Normal), 33 degrees C/20% RH (Hot 20%), 33 degrees C/40% RH (Hot 40%), 33 degrees C/60% RH (Hot 60%), and 33 degrees C/80% RH (Hot 80%). Blood samples were taken pre- and post-exercise and analyzed for noradrenaline (NA), adrenaline (ADR), dopamine (DA), serotonin (5-HT), 5 hydroxyindoleacetic acid (5-HIAA), and prolactin (PRL). Weight and oral and skin temperatures were recorded pre- and post-exercise. Heart rate was continuously monitored throughout the exercise. KEY FINDINGS: Hot 20%, Hot 40%, and Hot 80% had lower VO2max levels compared with Normal (P<0.05). The data pooled from all five conditions indicated that the NA (P<0.0001), PRL (P<0.0001), 5-HT (P=0.002), 5-HIAA (P=0.029), and DA (P=0.016) levels were affected by exercise. Accordingly, NA level was significantly associated with performance time. However, ADR did not show any significant effect between pre- and post-exercise (P=0.187). SIGNIFICANCE: The maximal aerobic capacity was impaired in high temperature and most humidity conditions. NA was strongly associated with exercise time, which suggested that exercise duration and intensity had an important influence on NA neurotransmitter level irrespective of the environmental conditions. PMID- 26367065 TI - HIV-1 Tat Protein Enhances Expression and Function of Breast Cancer Resistance Protein. AB - ATP binding cassette (ABC) transporters can transfer a variety of antiviral agents from the cytoplasm to body fluid, which results in a reduced intracellular concentration of the drugs. Proteins of HIV-1, e.g., Tat and gp120, altered some types of ABC transporter expression in brain microvascular endothelial cells and astrocytes. However, the effect of Tat on ABC transporters in T lymphocytes is unclear. In this study the status of breast cancer resistance protein (BCRP) in Tat expressing cell lines was examined with real-time PCR and flow cytometry. It was found that HIV-1 Tat protein upregulated BCRP expression and enhanced efflux mediated by BCRP significantly, which could inhibit antiviral drugs from entering infected cells and interfere with the therapeutic effect of HAART. PMID- 26367066 TI - Effect of irrigation, nitrogen application, and a nitrification inhibitor on nitrous oxide, carbon dioxide and methane emissions from an olive (Olea europaea L.) orchard. AB - Drip irrigation combined with nitrogen (N) fertigation is applied in order to save water and improve nutrient efficiency. Nitrification inhibitors reduce greenhouse gas emissions. A field study was conducted to compare the emissions of nitrous oxide (N2O), carbon dioxide (CO2) and methane (CH4) associated with the application of N fertiliser through fertigation (0 and 50kgNha(-1)), and 50kgNha( 1)+nitrification inhibitor in a high tree density Arbequina olive orchard. Spanish Arbequina is the most suited variety for super intensive olive groves. This system allows reducing production costs and increases crop yield. Moreover its oil has excellent sensorial features. Subsurface drip irrigation markedly reduced N2O and N2O+N2 emissions compared with surface drip irrigation. Fertiliser application significantly increased N2O+N2, but not N2O emissions. Denitrification was the main source of N2O. The N2O losses (calculated as emission factor) ranging from -0.03 to 0.14% of the N applied, were lower than the IPCC (2007) values. The N2O+N2 losses were the largest, equivalent to 1.80% of the N applied, from the 50kgNha(-1)+drip irrigation treatment which resulted in water filled pore space >60% most of the time (high moisture). Nitrogen fertilisation significantly reduced CO2 emissions in 2011, but only for the subsurface drip irrigation strategies in 2012. The olive orchard acted as a net CH4 sink for all the treatments. Applying a nitrification inhibitor (DMPP), the cumulative N2O and N2O+N2 emissions were significantly reduced with respect to the control. The DMPP also inhibited CO2 emissions and significantly increased CH4 oxidation. Considering global warming potential, greenhouse gas intensity, cumulative N2O emissions and oil production, it can be concluded that applying DMPP with 50kgNha(-1)+drip irrigation treatment was the best option combining productivity with keeping greenhouse gas emissions under control. PMID- 26367067 TI - Water addition, evaporation and water holding capacity of poultry litter. AB - Litter moisture content has been related to ammonia, dust and odour emissions as well as bird health and welfare. Improved understanding of the water holding properties of poultry litter as well as water additions to litter and evaporation from litter will contribute to improved litter moisture management during the meat chicken grow-out. The purpose of this paper is to demonstrate how management and environmental conditions over the course of a grow-out affect the volume of water A) applied to litter, B) able to be stored in litter, and C) evaporated from litter on a daily basis. The same unit of measurement has been used to enable direct comparison-litres of water per square metre of poultry shed floor area, L/m(2), assuming a litter depth of 5cm. An equation was developed to estimate the amount of water added to litter from bird excretion and drinking spillage, which are sources of regular water application to the litter. Using this equation showed that water applied to litter from these sources changes over the course of a grow-out, and can be as much as 3.2L/m(2)/day. Over a 56day grow out, the total quantity of water added to the litter was estimated to be 104L/m(2). Litter porosity, water holding capacity and water evaporation rates from litter were measured experimentally. Litter porosity decreased and water holding capacity increased over the course of a grow-out due to manure addition. Water evaporation rates at 25 degrees C and 50% relative humidity ranged from 0.5 to 10L/m(2)/day. Evaporation rates increased with litter moisture content and air speed. Maintaining dry litter at the peak of a grow-out is likely to be challenging because evaporation rates from dry litter may be insufficient to remove the quantity of water added to the litter on a daily basis. PMID- 26367068 TI - Synchronic interval Gaussian mixed-integer programming for air quality management. AB - To reveal the synchronism of interval uncertainties, the tradeoff between system optimality and security, the discreteness of facility-expansion options, the uncertainty of pollutant dispersion processes, and the seasonality of wind features in air quality management (AQM) systems, a synchronic interval Gaussian mixed-integer programming (SIGMIP) approach is proposed in this study. A robust interval Gaussian dispersion model is developed for approaching the pollutant dispersion process under interval uncertainties and seasonal variations. The reflection of synchronic effects of interval uncertainties in the programming objective is enabled through introducing interval functions. The proposition of constraint violation degrees helps quantify the tradeoff between system optimality and constraint violation under interval uncertainties. The overall optimality of system profits of an SIGMIP model is achieved based on the definition of an integrally optimal solution. Integer variables in the SIGMIP model are resolved by the existing cutting-plane method. Combining these efforts leads to an effective algorithm for the SIGMIP model. An application to an AQM problem in a region in Shandong Province, China, reveals that the proposed SIGMIP model can facilitate identifying the desired scheme for AQM. The enhancement of the robustness of optimization exercises may be helpful for increasing the reliability of suggested schemes for AQM under these complexities. The interrelated tradeoffs among control measures, emission sources, flow processes, receptors, influencing factors, and economic and environmental goals are effectively balanced. Interests of many stakeholders are reasonably coordinated. The harmony between economic development and air quality control is enabled. Results also indicate that the constraint violation degree is effective at reflecting the compromise relationship between constraint-violation risks and system optimality under interval uncertainties. This can help decision makers mitigate potential risks, e.g. insufficiency of pollutant treatment capabilities, exceedance of air quality standards, deficiency of pollution control fund, or imbalance of economic or environmental stress, in the process of guiding AQM. PMID- 26367069 TI - PAH dynamics in roadside environments: Influence on the consistency of diagnostic ratio values and ecosystem contamination assessments. AB - Roadside contamination (of air, soils and organisms) by polycyclic aromatic hydrocarbons (PAHs) was examined in an arable field and a mature forest (central France). Measured contents accounted for minute fractions of the cumulative vehicular exhaust emissions. The fate of vehicular PAHs was affected by many factors, including: atmospheric load dispersal, deposition on soils and vegetation, incorporation into water and organic matter cycles, and accumulation in species. Given these empirical results, we evaluated the consistency of a set of well-known diagnostic ratios. This effort has revealed that: i) most diagnostic ratio values vary considerably across roadside samples, including exhaust emissions; and ii) the first few meters from the carriageway or the road verge/forest interface or remote areas where surface water accumulates actually define turning or inflection points in the ratio profiles. These variations constitute a major obstacle to delimitating the extent of roadside contamination due to PAHs, in addition to raising questions over the applicability of ratios routinely used to designate sources. New ratios, namely (Flt+BkF)/(Pyr+BbF) and (Flt+BkF+BghiP)/Sigma10PAH, have been specifically developed to address this challenge. The higher consistencies exhibited among environmental compartments as well as between surface soil and exhaust emissions still yield differentiated values relative to several industrial sources. PMID- 26367070 TI - Presence of the HLADR13 allele among Mexican Mestizos suggests a protective factor against relapsing-remitting multiple sclerosis (RRMS). AB - BACKGROUND AND OBJECTIVE: Multiple sclerosis (MS) is a chronic demyelinating disease that affects the central nervous system. Researchers have looked for an association between relapsing-remitting MS (RRMS) and human leukocyte antigen (HLA) as risk or protective factor associated to ethnicity, which may add a partial explanation to disease heterogeneity and geographical variations. We described the frequency of the HLA-DR alleles in Mexican Mestizo (RRMS) patients. PATIENTS AND METHODS: We included 143 RRMS patients and 377 healthy controls, both Mexican Mestizos. Previous signing informed consent, we record demographic and clinical characteristics of the participants. Genetic profile was made, and HLA frequencies in both groups were compared. RESULTS: RRMS patients were 39.8% male and 60.2% female, mean age was 35 years. While, controls were 48%male and 52% women, mean age was 38 years. The most frequent allele found in subjects with RRMS was DR 15 (p=0.006, OR=2.2, 95% CI: 1.3-3.6). DR 13 allele was more frequent among healthy subjects than RRMS patients (p=0.050) with a protective OR 2.6, (95% CI: 1.3-5.2, p=0.050). CONCLUSION: In our study we found HLA DR 13 was more frequent in healthy controls than in RRMS patients, suggesting a protective factor among Mexican Mestizo population. PMID- 26367071 TI - Incidental benign cystic mesothelioma of the peritoneum: A case report. PMID- 26367072 TI - Rapid Covalent Fluorescence Labeling of Membrane Proteins on Live Cells via Coiled-Coil Templated Acyl Transfer. AB - Fluorescently labeled proteins enable the microscopic imaging of protein localization and function in live cells. In labeling reactions targeted against specific tag sequences, the size of the fluorophore-tag is of major concern. The tag should be small to prevent interference with protein function. Furthermore, rapid and covalent labeling methods are desired to enable the analysis of fast biological processes. Herein, we describe the development of a method in which the formation of a parallel coiled coil triggers the transfer of a fluorescence dye from a thioester-linked coil peptide conjugate onto a cysteine-modified coil peptide. This labeling method requires only small tag sequences (max 23 aa) and occurs with high tag specificity. We show that size matching of the coil peptides and a suitable thioester reactivity allow the acyl transfer reaction to proceed within minutes (rather than hours). We demonstrate the versatility of this method by applying it to the labeling of different G-protein coupled membrane receptors including the human neuropeptide Y receptors 1, 2, 4, 5, the neuropeptide FF receptors 1 and 2, and the dopamine receptor 1. The labeled receptors are fully functional and able to bind the respective ligand with high affinity. Activity is not impaired as demonstrated by activation, internalization, and recycling experiments. PMID- 26367074 TI - High intensity focused ultrasound treatment for non-neoplastic epithelial disorders of the vulva: Factors affecting effectiveness and recurrence. AB - OBJECTIVE: This paper investigates the effectiveness of high-intensity focused ultrasound (HIFU) for treating non-neoplastic epithelial disorders of the vulva (NNEDV) and to analyse the factors that affect the effectiveness of HIFU and recurrence. METHODS: This study included a total of 950 patients with pathologically confirmed NNEDV, who underwent HIFU treatment in our hospital between August 2008 and June 2013 and had completed follow-up data. Treatment efficacy and recurrence were evaluated retrospectively by analysing the patients' clinical pathological data and by following up their symptomatic changes. We also explored factors including age, status of menopause, HPV infection, lesion size, pathological type, and symptom severity for their correlation with treatment effectiveness and recurrence. RESULTS: HIFU was effective in alleviating symptoms and improving vulva signs, with a cure rate of 42.2%, an effective rate of 56.1%, and a low recurrence rate of 9.4%. No severe complications were recorded during or after the treatment. The treatment was statistically more effective in younger patients with squamous hyperplasia and smaller lesions than in older patients with lichen sclerosus and larger lesions (P < 0.05). Patients with a longer disease course or with lichen sclerosus had significantly higher recurrence rates than those with a shorter disease course or with squamous hyperplasia (P < 0.05). CONCLUSIONS: HIFU is safe and effective in treating NNEDV. Its effectiveness is correlated with age, size of lesion and pathological type, whereas post-treatment recurrence rates may be related to the duration of the disease and the pathological sub-types. PMID- 26367073 TI - COPD-Related Mortality and Co-morbidities in Northeastern Italy, 2008-2012: A Multiple Causes of Death Analysis. AB - INTRODUCTION: Analysis of COPD mortality based only on the underlying cause of death (UCOD) derived from death certificates underestimates disease burden. We analyzed the burden of COPD, as well as the pattern of reporting COPD and its co morbidities in death certificates, using multiple-cause of death (MCOD) records. METHODS: All 220,281 death certificates of decedents aged >= 40 years in the Veneto region (northeastern Italy) were analyzed through 2008-2012. The UCOD was selected by the Automated Classification of Medical Entities software. COPD was defined by ICD-10 codes J40-J44 and J47 based either on the UCOD or on any mention of COPD in death certificates (MCOD). Annual age-standardized COPD death rates were computed for 40-85 year-old subjects. RESULTS: COPD was mentioned in 7.9% (and selected as the UCOD in 2.7%) of death certificates. In about half of these, COPD was mentioned in Part II only. After circulatory and neoplastic diseases, the most frequent chronic diseases reported in certificates with any mention of COPD were diabetes (15.2%) and dementia/Alzheimer (8.9%). Between 2008 and 2012, age-standardized death rates (/100,000/year) decreased from 39.8 to 34.0 in males and from 12.7 to 11.3 in females in the UCOD analyses. These trends were confirmed, although figures were three times greater, in the MCOD analyses. CONCLUSIONS: MCOD analysis should be adopted to fully evaluate the burden of COPD related mortality. Our findings support a decreasing trend in COPD-related mortality in northeastern Italy between 2008 and 2012, in line with other recent studies in Europe and beyond. PMID- 26367075 TI - Inferring the economic standard of living and health from cohort height: Evidence from modern populations in developing countries. AB - Average adult height is a physical measure of the biological standard of living of a population. While the biological and economic standards of living of a population are very different concepts, they are linked and may empirically move together. If this is so, then cohort heights can also be used to make inferences about the economic standard of living and health of a population when other data are not available. We investigate how informative this approach is in terms of inferring income, nutrition, and mortality using data on heights from developing countries over the last 50 years for female cohorts born 1951-1992. We find no evidence that the absolute differences in adult height across countries are associated with different economic living standards. Within countries, however, faster increases in adult cohort height over time are associated with more rapid growth of GDP per capita, life expectancy, and nutritional intake. Using our instrumental variable approach, each centimeter gain in height is associated with a 6% increase in income per capita, a reduction in infant mortality of 7 per thousand (or an 1.25 year increase in life expectancy), and an increase in nutrition of 64 calories and 2 grams of protein per person per day relative to the global trend. We find that increases in cohort height can predict increases in income even for countries not used in the estimation of the relationship. This suggests our approach has predictive power out of sample for countries where we lack income and health data. PMID- 26367076 TI - IL17A gene polymorphism, serum IL17 and total IgE in Egyptian population with chronic HCV and hepatocellular carcinoma. AB - BACKGROUND: Chronic infections with HCV (CHC) induce a chronic inflammation which can lead to liver fibrosis and subsequently cirrhosis. A recent study suggests a role of IL-17 polymorphism and serum IL17 in hepatitis B related HCC. These data indicate that the IL-17 G-197A polymorphism may be a good indicator for susceptibility to cancer development. AIM: To investigate the role of the IL17A gene polymorphism, serum IL17 and total IgE in Egyptian population with chronic infections with HCV and HCC. SUBJECTS AND METHODS: This study was carried out on 40 patients with chronic HCV, 35 patients with hepatocellular carcinoma and 20 healthy persons as control. All subjects were submitted to History taking, clinical examination, abdominal ultrasound, laboratory tests including CBC, liver function tests, alpha fetoprotien, determination of IL17gene polymorphisms by PCR RFLP, IL17 by ELISA and IgE by immunonephelometric assay. RESULTS: In reference to AA genotype, the frequencies of GG, GA+GG genotypes in the cases with HCC were significantly different from that of the controls (p=0.012, 0.011) and carry 6.12,4.9 respectively fold increase for HCC risk and that of chronic HCV without HCC (p=0.005, 0.004) respectively. However, there was no significant difference in allele frequency in the studied groups (p=0.095). Cases with HCC significantly have higher levels of serum IL17 and IgE than both healthy control and chronic HCV. In conclusion, the present study showed the GG, GG+GA genotypes of IL17A gene is a risk factor for HCC development may be through increased IL17 and IgE and further studies with larger sample size and different populations are recommended. PMID- 26367077 TI - Transgenerational epigenetic inheritance: adaptation through the germline epigenome? AB - Epigenetic modifications direct the way DNA is packaged into the nucleus, making genes more or less accessible to transcriptional machinery and influencing genomic stability. Environmental factors have the potential to alter the epigenome, allowing genes that are silenced to be activated and vice versa. This ultimately influences disease susceptibility and health in an individual. Furthermore, altered chromatin states can be transmitted to subsequent generations, thus epigenetic modifications may provide evolutionary mechanisms that impact on adaptation to changed environments. However, the mechanisms involved in establishing and maintaining these epigenetic modifications during development remain unclear. This review discusses current evidence for transgenerational epigenetic inheritance, confounding issues associated with its study, and the biological relevance of altered epigenetic states for subsequent generations. PMID- 26367078 TI - Cidec promotes the differentiation of human adipocytes by degradation of AMPKalpha through ubiquitin-proteasome pathway. AB - BACKGROUND: We previously showed that Cidec was localized on the surface of lipid droplets and could promote the differentiation of human adipocytes, but the molecular mechanism was still unknown. METHODS & RESULTS: In this study, we first sought to identify proteins that interact with Cidec using yeast two-hybrid system. The results revealed that Cidec could directly interact with AMPKalpha1 subunit. We further showed that AMPKalpha levels decreased while Cidec increased during the adipogenic differentiation of human adipocytes. Meanwhile, we observed that the increased Cidec could reduce AMPKalpha level in adipocytes, and the downregulation of AMPKalpha could help to promote the differentiation of adipocytes. The results of co-immunoprecipitation and immunofluorescent proved that Cidec biochemically interacted and co-localized with AMPKalpha1, which meant Cidec was a regulator for AMPKalpha stability through an ubiquitin-proteasome pathway. CONCLUSION: Our data suggested that Cidec could interact with and down regulate AMPKalpha through an ubiquitin-proteasome degradation pathway, which provided a possible mechanism of Cidec in promoting human adipocytes differentiation. GENERAL SIGNIFICANCE: Our work proposed a new possible mechanism for human adipogenesis, and also provided a potential role of AMPKalpha as a target in treating obesity or obesity-related diseases. PMID- 26367081 TI - Lumbar Mechanics in Tennis Groundstrokes: Differences in Elite Adolescent Players With and Without Low Back Pain. AB - Adolescent tennis players are at risk for low back pain (LBP). Recent research has demonstrated a potential mechanical etiology during serves; however, groundstrokes have also been suggested to load this region. Therefore, this study compared lumbar mechanics between players with and without a history of LBP during open and square stance tennis forehands and backhands. Nineteen elite, adolescent, male tennis players participated, 7 with a history of recurrent disabling LBP and 12 without. Differences in three-dimensional lumbar kinetics and kinematics were compared between pain/no pain groups and groundstrokes using linear mixed models (P < .01). There were no significant differences between pain/no pain groups. Relative to a right-handed player, groundstroke comparisons revealed that forehands had greater racquet velocity, greater lumbar right lateral flexion force, as well as upper lumbar extension/rightward rotation and lower lumbar right rotation/lateral flexion movements that were closer to or further beyond end of range than backhands. Backhands required upper lumbar leftward rotation that was beyond end range, while forehands did not. Given that players typically rotated near to their end of range during the backswing of both forehands and backhands, independent of pain, groundstrokes may contribute to the cumulative strain linked to LBP in tennis players. PMID- 26367080 TI - Tropisetron attenuated the anxiogenic effects of social isolation by modulating nitrergic system and mitochondrial function. AB - BACKGROUND: Early social isolation stress (SIS) is associated with the occurrence of anxiety behaviors. It seems interaction between the nitrergic system and mitochondrial function plays a role in mediating the anxiety-like behaviors. In this study, we aimed to investigate the anxiolytic effects of tropisetron in animal model of SIS and we try to illustrate the possible role of nitrergic system and mitochondrial function. METHODS: We applied early social isolation paradigm to male NMRI mice. Animals treated with various doses of tropisetron, nitric oxide agents or their combination and anxiety-like behaviors of animals were assessed using valid behavioral tests including elevated plus maze (EPM), open-field test (OFT) and hole-board test (HBT) in their adulthood. Effects of housing conditions and drug treatments on the mitochondrial function were investigated in the hippocampus by assessing the ATP, GSH, ROS and nitrite levels. RESULTS: Anxiogenic effects of early SIS were assessed in the EPM, OFT, and HBT. Also, SIS disrupted mitochondrial function and caused oxidative stress in the hippocampus of stressed animals. Tropisetron showed an anxiolytic effect in the stressed mice. Also, these effects were mediated by nitrergic system by affecting mitochondrial function and modulating the oxidative stress. L-arginine, a nitric oxide precursor, abolished the anxiolytic effects of tropisetron in the behavioral tasks and blocked the protective effects of it against mitochondrial and oxidative challenge. CONCLUSIONS AND GENERAL SIGNIFICANCE: Our results demonstrated tropisetron attenuated the anxiogenic effects of SIS by mitigation of the negative effects of nitric oxide on mitochondrial function. PMID- 26367082 TI - Tissue time course and bioavailability of the pyrethroid insecticide bifenthrin in the Long-Evans rat. AB - 1. Pyrethroids are neurotoxic and parent pyrethroid appears to be toxic entity. This study evaluated the oral disposition and bioavailability of bifenthrin in the adult male Long-Evans rat. 2. In the disposition study, rats were administered bifenthrin (0.3 or 3 mg/kg) by oral gavage and serially sacrificed (0.25 h to 21 days). Blood, liver, brain and adipose tissue were removed. In the bioavailability study, blood was collected serially from jugular vein cannulated rats (0.25 to 24 h) following oral (0.3 or 3 mg/kg) or intravenous (0.3 mg/kg) administration of bifenthrin. Tissues were extracted and analyzed for bifenthrin by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). 3. Bifenthrin concentration in blood and liver peaked 1-2-h postoral administration and were approximately 90 ng/ml (or g) and 1000 ng/ml (or g) for both tissues at 0.3 and 3 mg/kg, respectively. Bifenthrin was rapidly cleared from both blood and liver. Brain concentrations peaked at 4-6 h and were lower than in blood at both doses (12 and 143 ng/g). Bifenthrin in adipose tissue peaked at the collected time points of 8 (157 ng/g) and 24 (1145 ng/g) h for the 0.3 and 3 mg/kg doses, respectively and was retained 21 days postoral administration. Following intravenous administration, the blood bifenthrin concentration decreased bi-exponentially, with a distribution half-life of 0.2 h and an elimination half-life of 8 h. Bifenthrin bioavailability was approximately 30%. These disposition and kinetic bifenthrin data may decrease uncertainties in the risk assessment for this pyrethroid insecticide. PMID- 26367083 TI - Managing Delirium In The Emergency Department: Tools For Targeting Underlying Etiology. AB - Delirium represents the complex junction between vulnerable patients, medical conditions, and environmental factors. Given the varied presentations of this disorder and the emergency department clinical environment, recognition and treatment may be challenging. Delirium can be diagnosed using validated standardized screening tools such as the Confusion Assessment Method. Management of delirium is directed towards rapidly treating the underlying medical condition while preventing and managing the behavioral symptoms with nonpharmacological (first-line) and pharmacological (second-line) interventions. In the severely agitated patient, pharmacological treatment tailored to the patient's age and comorbidities may be required as the initial treatment to facilitate evaluation and management of the underlying medical condition. Effective risk stratification and triage tools can positively impact patient and staff safety, as well as patient outcomes. PMID- 26367085 TI - Ocular involvement in systemic lupus erythematosus. AB - PURPOSE OF REVIEW: Many patients suffer from the ocular manifestations associated with systemic lupus erythematosus (SLE). Retinal vasculitis and optic neuritis are two of the most vision-threatening complications that can be associated with the disease. Ocular manifestations are often associated with wide-spread systemic inflammation which can be fatal. Thus, immediate recognition and treatment is vital for a positive outcome. RECENT FINDINGS: There is an array of medications available to ophthalmologists for treating the ocular manifestations of SLE. Treating the underlying systemic disease is crucial, as well as treating the active ocular complications. Recently, more attention has been placed on evaluating biologic agents' efficacy in treating the systemic condition. New therapies continue to emerge that have the potential to provide benefit to patients suffering from SLE. SUMMARY: SLE is a serious systemic condition that may first present with ocular manifestations. Thus, it is crucial for ophthalmologists to be equipped with the knowledge to detect and adequately treat the disorder to avoid vision/life-threatening complications. More research is needed to determine which therapy provides the best outcome for patients with limited side-effects. PMID- 26367084 TI - Extreme mitogenomic divergence between two syntopic specimens of Arremon aurantiirostris (Aves: Emberizidae) in central Panama suggests possible cryptic species. AB - We report the complete mitochondrial genome of two specimens of Orange-billed Sparrow Arremon aurantiirostris from Colon Province, in central Panama. The two specimens were collected on the same day, and at the same locality; however, they showed substantial divergence (6.3% average pairwise divergence among coding genes). A survey of ND2 sequence variation across Panama suggests that this divergence is the result of geographic differentiation and secondary contact. This high level of mitochondrial divergence among co-occurring individuals raises the possibility of multiple biological species in Orange-billed Sparrows. Our results are yet another demonstration that much remains to be discovered regarding avian biodiversity in Panama and throughout the Neotropics. PMID- 26367086 TI - Should patients with optic neuritis be treated with steroids? AB - PURPOSE OF REVIEW: Optic neuritis is the most common cause of optic neuropathy in young adults. High-dose intravenous corticosteroids (IVCS) were established as the standard of treatment for acute optic neuritis via the Optic Neuritis Treatment Trial (ONTT), with its first findings published more than 20 years ago. Subsequent studies have further clarified the role of corticosteroids in the treatment of acute optic neuritis. RECENT FINDINGS: Recent clinical research has confirmed existing knowledge of the efficacy and limitations of corticosteroids in the treatment of optic neuritis. Recent studies have examined the role of race, route of administration and combination of IVCS with other therapies. Current evidence continues to support high-dose IVCS as the cornerstone of treatment of acute optic neuritis. SUMMARY: High-dose IVCS are effective in hastening visual recovery in acute typical optic neuritis, but do not affect the final visual outcome. In optic neuritis patients, IVCS may delay progression to clinically definite multiple sclerosis (CDMS) at 2 years, but not at 5 or 10 years. It is reasonable to recommend high-dose IVCS for acute optic neuritis patients with significant vision loss, severe pain and/or white matter lesions on brain MRI in whom the potential for benefit outweighs the risks. PMID- 26367079 TI - Endostatin's emerging roles in angiogenesis, lymphangiogenesis, disease, and clinical applications. AB - BACKGROUND: Angiogenesis is the process of neovascularization from pre-existing vasculature and is involved in various physiological and pathological processes. Inhibitors of angiogenesis, administered either as individual drugs or in combination with other chemotherapy, have been shown to benefit patients with various cancers. Endostatin, a 20-kDa C-terminal fragment of type XVIII collagen, is one of the most potent inhibitors of angiogenesis. SCOPE OF REVIEW: We discuss the biology behind endostatin in the context of its endogenous production, the various receptors to which it binds, and the mechanisms by which it acts. We focus on its inhibitory role in angiogenesis, lymphangiogenesis, and cancer metastasis. We also present emerging clinical applications for endostatin and its potential as a therapeutic agent in the form a short peptide. MAJOR CONCLUSIONS: The delicate balance between pro- and anti-angiogenic factors can be modulated to result in physiological wound healing or pathological tumor metastasis. Research in the last decade has emphasized an emerging clinical potential for endostatin as a biomarker and as a therapeutic short peptide. Moreover, elevated or depressed endostatin levels in diseased states may help explain the pathophysiological mechanisms of the particular disease. GENERAL SIGNIFICANCE: Endostatin was once sought after as the 'be all and end all' for cancer treatment; however, research throughout the last decade has made it apparent that endostatin's effects are complex and involve multiple mechanisms. A better understanding of newly discovered mechanisms and clinical applications still has the potential to lead to future advances in the use of endostatin in the clinic. PMID- 26367087 TI - Ocular toxoplasmosis: background and evidence for an antibiotic prophylaxis. AB - PURPOSE OF REVIEW: The purpose of this review was to provide an overview of current data on antibiotic prophylaxis in ocular toxoplasmosis. RECENT FINDINGS: Studies showing the prophylactic effect of long-term antibiotics are discussed. Prophylaxis seems to be justified in patients with a high risk of recurrence because of antibiotic's potential side-effects. Therefore, predisposing factors leading to a higher risk of recurrence and the time period during which an antibiotic prophylaxis is most appropriate are reviewed. Finally, a patient individualized treatment recommendation is summarized. SUMMARY: In the current literature, two prospective, randomized case-control studies exist, which show the protective effect of an antibiotic prophylaxis. Hematologic, gastrointestinal and dermatologic complications are potential side-effects. Especially during the first year after suffering a recurrence, an antibiotic prophylaxis seems to be justified. The risk of a recurrence is inter alia influenced by the duration of the disease, the immune status of the host and the patient's age. Therefore, an antibiotic prophylaxis should be considered for patients who have recently been infected with ocular toxoplasmosis, for middle-aged and elderly patients and patients with a compromised immune system. This should be discussed with each patient individually, especially if the lesion is close to the macula. PMID- 26367088 TI - Treatment of neuromyelitis optica. AB - PURPOSE OF REVIEW: Neuromyelitis optica (NMO) is an antibody-mediated inflammatory disease of the central nervous system with a predilection for the optic nerves, spinal cord and certain brain regions. It has a distinct pathogenesis relating to aquaporin-4 autoimmunity and complement-mediated injury. This knowledge has translated into targeted efforts to develop novel, disease specific treatments. In this review, we discuss evidence supporting the use of currently available treatments for acute exacerbations and for long-term disease modification. We also discuss the risks and benefits of available and emerging immunotherapies. RECENT FINDINGS: Early, accurate diagnosis of NMO with appropriate acute and long-term immunosuppressive treatment is of prime importance for the prevention of disability associated with this disease. Standard measures for the management of acute exacerbations include intravenous methylprednisolone and plasmapheresis. First-line, long-term immunotherapies for NMO include azathioprine, mycophenolate mofetil and rituximab. Three randomized controlled treatment trials evaluating these agents are currently being conducted. In addition, there are numerous emerging therapies that are based upon current understanding of the disease immunopathogenesis. SUMMARY: NMO is an autoimmune disease that is separate from multiple sclerosis. Better understanding of its antibody and complement-dependent pathophysiology has proven to be critical for the formulation of current and future treatment strategies. PMID- 26367089 TI - Sjogren syndrome: what and where are we looking for? AB - PURPOSE OF REVIEW: Sjogren's syndrome affects exocrine glands leading to a dry mouth and dry eyes. Dry eye manifestations can precede the diagnosis of Sjogren's syndrome by many years. Innumerous spontaneous and inducible Sjogren's syndrome models have been used to study the pathogenesis of Sjogren's syndrome. This review focuses on recent human data, ocular and extraglandular manifestations of animal models, what is known, what is still unknown and how we need to look, and their correlation correspondence to human disease. RECENT FINDINGS: Hallmarks of dry eye in Sjogren's syndrome include increased corneal staining, goblet cell loss and low tear volume. Confocal microscopy and impression cytology are able to clarify new markers of the ocular disease. Extraglandular manifestations should be an alert more severe complications in the eye. Some models have strong sex and exocrine gland predilection, whereas aging generally worsens the disease phenotype. Although most models do not display a significant increase in corneal staining or tear secretion impairment, conjunctival infiltration and decrease in goblet cells are frequently seen. SUMMARY: We have seen great advances in the role of inflammation in ocular, oral and extra-glandular manifestations of Sjogren's syndrome. Several mechanisms and mediators of Sjogren's syndrome have been elucidated in animal model studies. PMID- 26367090 TI - Management of orbital IgG4-related disease. AB - PURPOSE OF REVIEW: IgG4-related disease (IgG4-RD) is a systemic process that can cause significant orbital disease. It can affect both sexes and all ages, with irreversible consequences if left untreated. Diagnosis is currently based upon a combination of clinical and imaging evidence of tissue swelling or mass, serum evidence of elevated IgG4 levels and histopathologic evidence of inappropriate IgG4 presence. The cause of IgG4-RD is as of yet unclear; this lack of understanding and the dearth of prospective studies have limited our ability to manage patients effectively. In this review, we discuss the most recent published evidence regarding best-practice management of IgG4-related orbital disease. RECENT FINDINGS: Recent literature remains retrospective, and has focused on the use of corticosteroid therapy as a first-line treatment. Rituximab infusions have also received significant attention, among other second-line agents. Radiation therapy has been reported to be effective. Long-term monitoring for relapse, involvement of other organ systems and potential neoplastic transformation is required. SUMMARY: The management of orbital IgG4-RD will gain from more targeted therapy in the future as the underlying cause is better understood. In the meantime, randomized, controlled trials of varying treatment regimens would be of benefit. PMID- 26367091 TI - Local (topical and intraocular) therapy for ocular Adamantiades-Behcet's disease. AB - PURPOSE OF REVIEW: The purpose of this review is to outline agents currently in use for the local anti-inflammatory therapy of ocular Adamantiades-Behcet's disease (ABD), as well as those in translation from the laboratory to clinical use. RECENT FINDINGS: Novel formulations and innovative intraocular delivery strategies have been recently applied to treat intraocular inflammation in ABD. SUMMARY: ABD is a chronic multisystemic vasculitic disease with the highest prevalence in the Mediterranean basin and in the Eastern region of Asia. Bilateral autoimmune uveitis, oral and genital aphthous and skin lesions are the historically described triad. ABD uveitis is chronic relapsing and often sight threatening and, according to the actual guidelines, to limit posterior segment involvement and prevent visual impairment high-dose and long-term systemic anti inflammatory treatment is indicated. Corticosteroids, both topically and systemically, are the most effective treatment in the acute phase. To overcome the well known side-effects of corticosteroids over the long period, steroid sparing drugs have been systemically administered showing positive results but having limited safety profile. To potentiate the intraocular pharmacological efficacy of these molecules in refractory ABD uveitis and to circumvent the risks of systemic administration, novel topical and intravitreal formulations and innovative delivering systems have been recently developed. PMID- 26367092 TI - Primary CNS lymphoma. AB - PURPOSE OF REVIEW: Despite recent progress, the diagnosis of primary CNS lymphoma (PCNSL) remains a challenge and is often delayed by several months. Treatment options are still debated and the prognosis of PCNSL lymphoma is poor for most patients. This review will describe recent progress and future orientations for diagnosis of PCNSL and report on the recent trends regarding therapeutic options. RECENT FINDINGS: PCNSL must be suspected in cases of chronic posterior uveitis, especially in patients over 50 years old. Diagnosis is based on cytology and molecular analysis of clonality of vitreous samples. Intraocular interleukin (IL) 10 level has proved to be a valuable tool for screening purposes in cases where there is a suspicion of primary vitreoretinal lymphoma. Intraocular cytokine dosage could also be a useful marker to follow the therapeutic response of patients with PCNSL. Treatment of PCNSL remains under debate. SUMMARY: Diagnosis of PCNSL is challenging. Suspicion relies on clinical history and on IL-10 and IL 6 levels in ocular fluid samples. Definite diagnosis is based on cytology and molecular analysis of clonality. New diagnostic and prognostic markers are currently evaluated. Whether isolated vitreoretinal lymphoma should be treated locally or with systemic treatment remains highly controversial. PMID- 26367093 TI - Management of acute cranial nerve 3, 4 and 6 palsies: role of neuroimaging. AB - PURPOSE OF REVIEW: This article will discuss the management of isolated, acute cranial nerve 3,4 and 6 palsies with special focus on the role of neuroimaging in older adults based on recently published data. RECENT FINDINGS: Acute cranial nerve palsies affecting the third, fourth or sixth cranial nerves in isolation or in combination with other neurological signs and symptoms can be due to a variety of causes such as ischemia, inflammation, infection and compression of the ocular motor nerves. Although neuroimaging is generally recommended in all individuals presenting with ocular motor nerve palsies that occur in association with other neurological signs and symptoms, the indications for neuroimaging in older individuals (age > 50 years) who present with acute isolated ocular motor nerve palsies are less clear and controversial. Past and recent studies have attempted to address this question. A recent prospective study found that overall 16.5% of adult patients presenting with acute ocular motor mononeuropathy had structural lesions on MRI scan and 4.6% with fourth and sixth nerve palsies and no risk factors were found to have positive MRI scans. SUMMARY: On the basis of recently published data, we recommend contrast-enhanced MRI for all patients presenting with acute, isolated ocular motor mononeuropathies irrespective of age. Studies have clearly shown a small but significant prevalence of important findings in this group of patients thus favoring neuroimaging at the time of diagnosis. PMID- 26367094 TI - Is there treatment for nonarteritic anterior ischemic optic neuropathy. AB - PURPOSE OF REVIEW: Nonarteritic anterior ischemic optic neuropathy (NAION) is the most common cause of an acute optic neuropathy over the age 50 with an annual incidence of 2-10/100 000. Most patients are left with a permanent decrease in visual acuity and visual field loss. No approved treatment has conclusively reversed the process or prevented a second event that typically involves the previously unaffected eye. Many medical and surgical treatments have been proposed with conflicting results. The goal of this review is to present current data in order to permit clinicians and patients to make an educated decision about treatment. RECENT FINDINGS: Recently, there has been a flurry of case reports, small clinical trials and testing in animal models of NAION for various treatments for NAION and this review attempts to present the data concisely with the authors' opinions about the reliability of the data. SUMMARY: To date, there is no class I evidence of benefit for the treatment of NAION; however, the aphorism attributed to Carl Sagan, PhD aptly applies: 'Absence of evidence is not evidence of absence'. PMID- 26367095 TI - The evolution of NPs and The Nurse Practitioner journal. PMID- 26367096 TI - Integrated breast cancer surgical treatment: novel aspects of minimally-invasive treatments. AB - The surgical management of breast cancer has been undergoing continuous and profound changes over the last 40 years. The evolution from aggressive and mutilating treatment to conservative approach has been long but constant, despite the controversies arising every time a new procedure came to light. Today, the esthetic satisfaction of breast cancer patients coupled with oncological safety is the goal of the modern breast surgeon. Breast-conserving surgery with adjuvant radiotherapy is considered the gold standard approach for patients with early stage breast cancer and the recent introduction of "oncoplastic techniques" has furtherly increased the use of breast-conserving procedures. Mastectomy still remains a valid surgical alternative in selected cases and is usually associated with immediate reconstructive procedures. New surgical procedures called "conservative mastectomies" are emerging as techniques that combine oncological safety and esthetic outcome by entirely removing the breast parenchyma sparing the breast skin and nipple-areola complex. Staging of the axilla has also gradually evolved toward less aggressive approaches with the adoption of sentinel node biopsy and new therapeutic strategies are emerging in patients with a pathological positivity in sentinel lymph node biopsy. The present special article will highlight the new surgical treatment options, which are more and more effective and respectful of breast cancer patients. PMID- 26367097 TI - Impulse oscillometry in acute and stable asthmatic children: a comparison with spirometry. AB - OBJECTIVE: Lung function tests have attracted interest for the diagnosis and follow-up of childhood asthma in recent years. For patients who cannot perform forced expiratory maneuvers, impulse oscillometry (IOS), performed during spontaneous breathing, may be an alternative tool. METHODS: Thirty-five acute, 107 stable asthmatic and 103 healthy children who presented to our clinic performed IOS followed by spirometry before and after salbutamol inhalation. The mean baseline and reversibility of IOS and spirometry parameters were compared between the groups. Correlation analyses were undertaken within the asthmatics, and the healthy controls separately. To distinguish the three groups, the sensitivity and specificity of baseline and reversibility values of IOS and spirometry were computed. When spirometry was taken as the gold standard, the discriminating performance of IOS to detect the airway obstruction and reversibility was investigated. RESULTS: The mean absolute values of Zrs, R5, R5 R20, X5, X10, X15, Fres, AX, and all spirometric parameters, and the mean reversibility values of R5, R10, Fres, AX and forced expiratory volume in one second were different between the groups and the highest area under curve values to discriminate the groups was obtained from area of reactance (AX) and DeltaAX. Zrs, all resistance (including R5-R20) and reactance parameters, Fres and AX were correlated with at least one spirometric parameter. Spirometric reversibility was detected by <=-22.34 and <=-39.05 cut-off values of DeltaR5 and DeltaAX, respectively. CONCLUSIONS: IOS has shown a highly significant association with spirometric indices and reversibility testing. It may be a substitute for spirometry in children who fail to perform forced expiratory maneuvers. PMID- 26367098 TI - Plasma Pentraxin 3 Differentiates Nonalcoholic Steatohepatitis (NASH) from Non NASH. AB - BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) includes a variety of histopathological findings ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) which can only be differentiated by liver biopsy. There is yet no unique biomarker found to discriminate NASH from simple steatosis.We aimed to investigate the relationship of plasma pentraxin 3 (PTX3) and its main stimulant tumor necrosis factor alpha (TNF-alpha) with the degree of liver damage in NAFLD. METHODS: Plasma PTX3 and TNF-alpha levels were measured in 70 patients with histologically verified NAFLD (56 with NASH, 14 with non-NASH) and 12 controls. RESULTS: PTX3 and TNF-alpha levels were found significantly higher in the NAFLD group than in the control group (4.1 +/- 2.3 vs. 1.3 +/- 0.8 ng/mL, P < 0.001, and 7.6 +/- 4.1 vs. 3.3 +/- 1.3 pg/mL, P < 0.001 respectively) and in biopsy proven NASH subgroup than non-NASH subgroup (4.6 +/- 2.2 vs. 2.2 +/- 1.7 ng/mL, P = 0.001, and 8.3 +/- 4.3 vs. 4.6 +/- 1.6 pg/mL, P = 0.001 respectively). To discriminate NASH from non-NASH PTX3 had 91.1% sensitivity and 71.4% specificity at the cutoff value of 2.45 ng/mL. Plasma PTX3 levels showed correlation with NAFLD activity score, fibrosis stage and steatosis grade (r = 0.659, P < 0.001; r = 0.354, P < 0.01; and r = 0.455, P < 0.001, respectively). CONCLUSION: This study demonstrated markedly higher PTX3 levels in NAFLD patients compared with controls, and in biopsy proven NASH patients compared with non-NASH ones. Thus, in this cohort we showed that plasma PTX3 may be a promising biomarker for the presence of NASH. PMID- 26367099 TI - Reduced aspirin responsiveness as assessed by impedance aggregometry is not associated with adverse outcome after cardiac surgery in a small low-risk cohort. AB - Reduced aspirin responsiveness (i.e. persistent high platelet reactivity in platelet function testing) might be associated with increased risk of myocardial ischemia and cardiac mortality in patients with coronary disease. However, the impact in patients undergoing coronary artery bypass grafting (CABG) is unclear. The aim of this prospective cohort study was to evaluate the predictive value of reduced aspirin responsiveness on cardiac and thromboembolic events in patients undergoing elective isolated CABG surgery with aspirin intake until at least two days before surgery. We included 304 patients in this prospective single-center cohort study. Impedance platelet aggregometry (Multiplate(r)) was performed directly before and on the first day after surgery. Reduced aspirin responsiveness was defined as area under the curve in ASPItest (AUCASPI) >=300 U. The primary outcome was a composite of all-cause mortality and/or major adverse cardiac or thromboembolic events within 1 year. Reduced aspirin responsiveness was found in 13 and 24% of patients pre and postoperatively, respectively. There was no difference in the outcomes between patients with normal and reduced aspirin responsiveness in the preoperative measurement (log-rank test, p = 0.540). Multivariate analysis including logistic EuroSCORE I and postoperative troponin T levels did not show any association of reduced aspirin responsiveness with adverse outcome (hazard ratio, 0.576; (95% CI 0.128-2.585; p = 0.471). Similarly, postoperative reduced aspirin responsiveness was not associated with adverse events. To conclude, reduced aspirin responsiveness as evaluated by Multiplate(r) platelet function analyzer was not associated with increased incidence of major adverse cardiac and thromboembolic events and mortality after CABG surgery. PMID- 26367100 TI - New insights into the pathogenesis of giant cell arteritis and hopes for the clinic. AB - Giant cell arteritis is a complex immune-mediated disease that involves large blood vessels in individuals older than 50 years. Recent studies have confirmed a strong association of this form of vasculitis with the HLA region, particularly with HLA class II genes. However, other non-HLA loci, such as protein tyrosine phosphatase non-receptor type 22, may also account for the susceptibility to giant cell arteritis. In addition, genetic variants located in genes encoding proinflammatory cytokines seem to influence the phenotypic expression of the disease, including the risk of severe ischemic complications, the presence of polymyalgia rheumatica and the higher incidence of relapses observed in some patients. The identification of putative genetic markers of disease severity could have clear therapeutic implications, as it may allow us to identify patients who are potentially responders to specific treatments. PMID- 26367102 TI - Comparing the characteristics of people living with and without HIV in long-term care and home care in Ontario, Canada. AB - Population aging and successful drug therapy in human immunodeficiency virus (HIV) management mean that more people are living longer with HIV. As these individuals age, they become more at risk of developing other chronic health conditions which will have many implications for disease management and choice of care setting. As people living with HIV turn to home care and long-term care (LTC) settings for care, understanding the particular needs of this population is becoming increasingly important. This study sought to describe the sociodemographic, clinical, and social attributes of people living with HIV in the home care and institutional environments. This work involved secondary analysis of data collected from both the international Resident Assessment Instruments (interRAI) home care and minimum data set instruments in the Canadian province of Ontario. Descriptive analysis was used to describe key attributes of people living with and without HIV in LTC, complex continuing care, and home care settings. A comparison of differences between people living with HIV across the three environments was also done using Chi-square analysis. People living with HIV were often younger, male and unmarried than other populations in the care settings studied. Together with specific health needs associated with issues like mental health and social isolation, people living with HIV represent a population with complex and distinctive health needs. Finding ways to better understand the needs of this vulnerable population will help to develop strategies to provide better formal and informal care and improve the quality of life of this group. interRAI standardized assessment instruments may be important tools for meeting this challenge. PMID- 26367101 TI - Streptococcus pneumoniae pharyngeal colonization in school-age children and adolescents with cancer. AB - Patients with cancer, particularly those with hematologic malignancies, are at an increased risk of invasive pneumococcal disease (IPD) and they are included in the list of subjects for whom pneumococcal vaccination is recommended. The main aim of this study was to evaluate Streptococcus pneumoniae colonization in school aged children and adolescents with cancer to determine the potential protective efficacy of 13-valent pneumococcal conjugate vaccine (PCV13). An oropharyngeal swab was obtained from 277 patients (age range 6-17 years) with cancer during routine clinical visits and analyzed for S. pneumoniae using real-time polymerase chain reaction. S. pneumoniae was identified in 52 patients (18.8%), including 47/235 (20.0%) with hematologic malignancies and 5/42 (11.9%) with solid tumors. Colonization declined significantly with an increase in age (odds ratio [OR] 0.34, 95% confidence interval [CI] 0.16-0.71, and OR 0.30, 95% CI 0.11-0.82 in children aged 10-14 and >=15 years, respectively, as compared to those <10 years). Carriage was more common among patients with leukemia or lymphoma than in children with solid tumors. Co-trimoxazole prophylaxis was significantly associated with reduced pneumococcal carriage (OR 0.41, 95% CI 0.19-0.89). A total of 15/58 (25.9%) and 26/216 (12.0%) children were colonized by PCV13 serotypes among cancer patients previously vaccinated and not vaccinated with 7 valent pneumococcal conjugate vaccine (PCV7), respectively. In conclusion, this study indicates that children and adolescents with cancer are frequently colonized by S. pneumoniae. Because most of the carried serotypes are included in PCV13, this vaccine is presently the best solution to reduce the risk of IPD in these patients. PMID- 26367103 TI - Giant Spin Pumping and Inverse Spin Hall Effect in the Presence of Surface and Bulk Spin-Orbit Coupling of Topological Insulator Bi2Se3. AB - Three-dimensional (3D) topological insulators are known for their strong spin orbit coupling (SOC) and the existence of spin-textured surface states that might be potentially exploited for "topological spintronics." Here, we use spin pumping and the inverse spin Hall effect to demonstrate successful spin injection at room temperature from a metallic ferromagnet (CoFeB) into the prototypical 3D topological insulator Bi2Se3. The spin pumping process, driven by the magnetization dynamics of the metallic ferromagnet, introduces a spin current into the topological insulator layer, resulting in a broadening of the ferromagnetic resonance (FMR) line width. Theoretical modeling of spin pumping through the surface of Bi2Se3, as well as of the measured angular dependence of spin-charge conversion signal, suggests that pumped spin current is first greatly enhanced by the surface SOC and then converted into a dc-voltage signal primarily by the inverse spin Hall effect due to SOC of the bulk of Bi2Se3. We find that the FMR line width broadens significantly (more than a factor of 5) and we deduce a spin Hall angle as large as 0.43 in the Bi2Se3 layer. PMID- 26367104 TI - Mobilizing a Statewide Network to Provide Ebola Education and Support. AB - BACKGROUND: Healthcare providers require the latest information and procedures when a public health emergency arises. During the fall of 2014, when the Ebola virus was first identified in a patient in the United States, education about Ebola virus disease (EVD) and procedures for its identification and control needed widespread and immediate dissemination to healthcare providers. In addition, there was a need to allay fears and reassure the public and providers that a process was in place to manage Ebola should it arrive in Arkansas. The state health department engaged multiple interest groups and provided a variety of educational and management activities. The Arkansas Department of Health and the only academic medical center in the state began offering time-consuming, one on-one education over the phone, which reached too few providers. A solution was needed to educate many providers across the state in the protocols for identification, isolation, and management of patients with EVD. In response, the Arkansas Department of Health and the University of Arkansas for Medical Sciences leveraged the interactive video and Webinar capabilities of the state's telemedicine network to educate both providers and the public of this public health emergency. MATERIALS AND METHODS: Six interactive video events were staged over 5 days in October 2014. RESULTS: In six events, 82 individual healthcare facilities (67 of which were hospitals) and 378 providers attended via the Webinar option, whereas 323 healthcare professionals received continuing education credits. CONCLUSIONS: A statewide videoconferencing infrastructure can be successfully mobilized to provide timely public health education and communication to healthcare providers and the public in multiple disciplines and practice settings. PMID- 26367105 TI - Independent Evaluation of Middle School-Based Drug Prevention Curricula: A Systematic Review. AB - IMPORTANCE: Lack of robust program evaluation has hindered the effectiveness of school-based drug abuse prevention curricula overall. Independently evaluated randomized controlled trials (RCTs) of universal, middle school-based drug abuse prevention curricula are the most useful indicators of whether such programs are effective or ineffective. OBJECTIVE: To conduct a systematic review identifying independently evaluated RCTs of universal, middle school-based drug abuse prevention curricula; extract data on study quality and substance use outcomes; and assess evidence of program effectiveness. EVIDENCE REVIEW: PsycInfo, Educational Resources Information Center, Science Citation Index, Social Science Citation Index, Cumulative Index to Nursing and Allied Health Literature, MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews were searched between January 1, 1984, and March 15, 2015. Search terms included variations of drug, alcohol, tobacco, and marijuana use, as well as school, prevention, and effectiveness. Studies included in the review were RCTs carried out by independent evaluators of universal school-based drug prevention curricula available for dissemination in the United States that reported alcohol, tobacco, marijuana, or other drug use outcomes. Two researchers extracted data on study quality and outcomes independently using a data extraction form and met to resolve disagreements. FINDINGS: A total of 5071 publications were reviewed, with 13 articles meeting final inclusion criteria. Of the 13 articles, 6 RCTs of 4 distinct school-based curricula were identified for inclusion. Outcomes were reported for 42 single-drug measures in the independent RCTs, with just 3 presenting statistically significant (P < .05) differences between the intervention group and the control group. One program revealed statistically significant positive effects at final follow-up (Lions-Quest Skills for Adolescence). CONCLUSIONS AND RELEVANCE: The results of our review demonstrate the dearth of independent research that appropriately evaluates the effectiveness of universal, middle school-based drug prevention curricula. Independent evaluations show little evidence of effectiveness for widely used programs. New methods may be necessary to approach school-based adolescent drug prevention. PMID- 26367106 TI - Hierarchically arranged helical fibre actuators driven by solvents and vapours. AB - Mechanical responsiveness in many plants is produced by helical organizations of cellulose microfibrils. However, simple mimicry of these naturally occurring helical structures does not produce artificial materials with the desired tunable actuations. Here, we show that actuating fibres that respond to solvent and vapour stimuli can be created through the hierarchical and helical assembly of aligned carbon nanotubes. Primary fibres consisting of helical assemblies of multiwalled carbon nanotubes are twisted together to form the helical actuating fibres. The nanoscale gaps between the nanotubes and micrometre-scale gaps among the primary fibres contribute to the rapid response and large actuation stroke of the actuating fibres. The compact coils allow the actuating fibre to rotate reversibly. We show that these fibres, which are lightweight, flexible and strong, are suitable for a variety of applications such as energy-harvesting generators, deformable sensing springs and smart textiles. PMID- 26367107 TI - Durable protein lattices of clathrin that can be functionalized with nanoparticles and active biomolecules. AB - Biological molecules that self-assemble and interact with other molecules are attractive building blocks for engineering biological devices. DNA has been widely used for the creation of nanomaterials, but the use of proteins remains largely unexplored. Here, we show that clathrin can form homogeneous and extended two-dimensional lattices on a variety of substrates, including glass, metal, carbon and plastic. Clathrin is a three-legged protein complex with unique self assembling properties and is relevant in the formation of membrane transport vesicles in eukaryotic cells. We used a fragment of the adaptor protein epsin to immobilize clathrin lattices on the substrates. The lattices span multiple square millimetres with a regular periodicity of 30 nm and can be functionalized via modified subunits of clathrin with either inorganic nanoparticles or active enzymes. The lattices can be stored for months after crosslinking and stabilization with uranyl acetate. They could be dehydrated and rehydrated without loss of function, offering potential applications in sensing and as biosynthetic reactors. PMID- 26367108 TI - Antenna-coupled photon emission from hexagonal boron nitride tunnel junctions. AB - The ultrafast conversion of electrical signals to optical signals at the nanoscale is of fundamental interest for data processing, telecommunication and optical interconnects. However, the modulation bandwidths of semiconductor light emitting diodes are limited by the spontaneous recombination rate of electron hole pairs, and the footprint of electrically driven ultrafast lasers is too large for practical on-chip integration. A metal-insulator-metal tunnel junction approaches the ultimate size limit of electronic devices and its operating speed is fundamentally limited only by the tunnelling time. Here, we study the conversion of electrons (localized in vertical gold-hexagonal boron nitride-gold tunnel junctions) to free-space photons, mediated by resonant slot antennas. Optical antennas efficiently bridge the size mismatch between nanoscale volumes and far-field radiation and strongly enhance the electron-photon conversion efficiency. We achieve polarized, directional and resonantly enhanced light emission from inelastic electron tunnelling and establish a novel platform for studying the interaction of electrons with strongly localized electromagnetic fields. PMID- 26367109 TI - Anti-icing potential of superhydrophobic Ti6Al4V surfaces: ice nucleation and growth. AB - On the basis of the icing-delay performance and ice adhesion strength, the anti icing potential of the superhydrophobic surface has been well-investigated in the past few years. The present work mainly emphasized the investigations of ice nucleation and growth to fully explore the anti-icing potential of the superhydrophobic surface. We took the various surfaces ranging from hydrophilic to superhydrophobic as the research objects and, combining the classical nucleation theory, discussed the ice nucleation behaviors of the water droplets on these sample surfaces under the condition of supercooling. Meanwhile, the macroscopical growth processes of ice on these surfaces were analyzed on the basis of the growth mechanism of the ice nucleus. It was found that the superhydrophobic surface could greatly reduce the solid-liquid interface nucleation rate, owing to the extremely low actual solid-liquid contact area caused by the composite micro-nanoscale hierarchical structures trapping air pockets, leading to the bulk nucleation dominating the entire ice nucleation at the lower temperatures. Furthermore, ice on the superhydrophobic surface possessed a lower macroscopical growth velocity as a result of the less ice nucleation rate and the insulating action of the trapped air pockets. PMID- 26367111 TI - Size-controllable DNA nanoribbons assembled from three types of reusable brick single-strand DNA tiles. AB - Precise control of nanostructure is a significant goal shared by supramolecular chemistry, nanotechnology and materials science. In DNA nanotechnology, methods of constructing desired DNA nanostructures using programmable DNA strands have been studied extensively and have become a promising branch of research, but developing universal and low-cost (in the sense of using fewer types of DNA strands) methods remains a challenge. In this work, we propose a novel approach to assemble size-controllable DNA nanoribbons with three types of reusable brick SSTs (single-stranded DNA tiles), where the control of ribbon size is achieved by regulating the concentration ratio between manipulative strands and packed single stranded DNA tiles. In our method, three types of brick SSTs are sufficient in assembling DNA nanoribbons of different sizes, which is much less than the number of types of unique tile-programmable assembling strategy, thus achieving a universal and low-cost method. The assembled DNA nanoribbons are observed and analyzed by atomic force microscopy (AFM). Experimental observations strongly suggest the feasibility and reliability of our method. PMID- 26367112 TI - MiR-634 decreases cell proliferation and induces apoptosis by targeting mTOR signaling pathway in cervical cancer cells. AB - Taking the emergence of continuous resistance to chemotherapy and the evidence that miRNAs are associated with chemoresistance in cancers into consideration, it is of significant importance to reveal the miRNAs functions for the treatment of cancer. As a novel tumor suppressor, MiR-634 is known to induce apoptosis in tumor cell which is essential for tumorigenesis. Herein, we elucidated the regulation effects of miR-634 in gene expression and discovery of its target gene in cell proliferation and invasion that would aid therapeutic apoptosis. As a result, by targeting mTOR signal pathway, miR-634 inhibited cell proliferation, migration and invasiveness in cervical cancer cells and the block of miR-634 enhances the mTOR expression at both the mRNA and protein levels which regulated the expression of mTOR negatively. Taken together, these results further indicated that miR-634 is an effective target for cancer treatment, and the findings provided in this work might lead to the better understanding of the malignant behavior of cervical carcinoma. PMID- 26367113 TI - Vestibular Implants: 8 Years of Experience with Electrical Stimulation of the Vestibular Nerve in 11 Patients with Bilateral Vestibular Loss. AB - BACKGROUND: The concept of the vestibular implant is primarily to artificially restore the vestibular function in patients with a bilateral vestibular loss (BVL) by providing the central nervous system with motion information using electrical stimulation of the vestibular nerve. Our group initiated human trials about 10 years ago. METHODS: Between 2007 and 2013, 11 patients with a BVL received a vestibular implant prototype providing electrodes to stimulate the ampullary branches of the vestibular nerve. Eye movements were recorded and analyzed to assess the effects of the electrical stimulation. Perception induced by electrical stimulation was documented. RESULTS: Smooth, controlled eye movements were obtained in all patients showing that electrical stimulation successfully activated the vestibulo-ocular pathway. However, both the electrical dynamic range and the amplitude of the eye movements were variable from patient to patient. The axis of the response was consistent with the stimulated nerve branch in 17 out of the 24 tested electrodes. Furthermore, in at least 1 case, the elicited eye movements showed characteristics similar to those of compensatory eye movements observed during natural activities such as walking. Finally, diverse percepts were reported upon electrical stimulation (i.e., rotatory sensations, sound, tickling or pressure) with intensity increasing as the stimulation current increased. CONCLUSIONS: These results demonstrate that electrical stimulation is a safe and effective means to activate the vestibular system, even in a heterogeneous patient population with very different etiologies and disease durations. Successful tuning of this information could turn this vestibular implant prototype into a successful artificial balance organ. PMID- 26367114 TI - Thermal instabilities and Rayleigh breakup of ultrathin silver nanowires grown in helium nanodroplets. AB - Ag nanowires with diameters below 6 nm are grown within vortex containing superfluid helium nanodroplets and deposited onto a heatable substrate at cryogenic temperatures. The experimental setup allows an unbiased investigation of the inherent stability of pristine silver nanowires, which is virtually impossible with other methods due to chemical processes or templates involved in standard production routes. We demonstrate by experiment and by adaption of a theoretical model that initially continuous wires disintegrate into chains of spheres. This phenomenon is well described by a Rayleigh-like breakup mechanism when the substrate is heated to room temperature. Our findings clarify the recent discussions on the cause of the observed segmented patterns, where a breakup during deposition [Gomez et al., Phys. Rev. Lett., 2012, 108, 155302] or mechanisms intrinsic to the helium droplet mediated growth process [Spence et al., Phys. Chem. Chem. Phys., 2014, 16, 6903] have been proposed. The experimental setup confirms the validity of previous suggestions derived from bulk superfluid helium experiments [Gordon et al., Phys. Chem. Chem. Phys., 2014, 16, 25229] for the helium droplet system, and further allows a much more accurate determination of the breakup temperature. PMID- 26367115 TI - Integrating Imaging into Clinical Practice in Inflammatory Bowel Disease. AB - Imaging is an important component for the monitoring of therapeutic success and disease control in patients with IBD. Colonoscopy is still the gold standard for imaging of disease activity. It is questionable, however, whether 'standard' or 'routine' imaging procedures max contribute to improved IBD therapy. There are good arguments for a problem driven imaging approach in IBD. Subsequently, the schedule of monitoring examinations should depend on the disease course (mild vs. severe) and the treatment used. Bowel ultrasound where available may substitute for endoscopy in many circumstances. New endoscopic techniques will be available at specialized centers for specific management questions. Applying these individualized strategies, imaging/monitoring will pay off for better disease control and better quality of life for IBD patients in the future. PMID- 26367116 TI - Robust Generalized Low Rank Approximations of Matrices. AB - In recent years, the intrinsic low rank structure of some datasets has been extensively exploited to reduce dimensionality, remove noise and complete the missing entries. As a well-known technique for dimensionality reduction and data compression, Generalized Low Rank Approximations of Matrices (GLRAM) claims its superiority on computation time and compression ratio over the SVD. However, GLRAM is very sensitive to sparse large noise or outliers and its robust version does not have been explored or solved yet. To address this problem, this paper proposes a robust method for GLRAM, named Robust GLRAM (RGLRAM). We first formulate RGLRAM as an l1-norm optimization problem which minimizes the l1-norm of the approximation errors. Secondly, we apply the technique of Augmented Lagrange Multipliers (ALM) to solve this l1-norm minimization problem and derive a corresponding iterative scheme. Then the weak convergence of the proposed algorithm is discussed under mild conditions. Next, we investigate a special case of RGLRAM and extend RGLRAM to a general tensor case. Finally, the extensive experiments on synthetic data show that it is possible for RGLRAM to exactly recover both the low rank and the sparse components while it may be difficult for previous state-of-the-art algorithms. We also discuss three issues on RGLRAM: the sensitivity to initialization, the generalization ability and the relationship between the running time and the size/number of matrices. Moreover, the experimental results on images of faces with large corruptions illustrate that RGLRAM obtains the best denoising and compression performance than other methods. PMID- 26367117 TI - Geochemical Evidence of the Seasonality, Affinity and Pigmenation of Solenopora jurassica. AB - Solenopora jurassica is a fossil calcareous alga that functioned as an important reef-building organism during the Palaeozoic. It is of significant palaeobiological interest due to its distinctive but poorly understood pink and white banding. Though widely accepted as an alga there is still debate over its taxonomic affinity, with recent work arguing that it should be reclassified as a chaetetid sponge. The banding is thought to be seasonal, but there is no conclusive evidence for this. Other recent work has, however demonstrated the presence of a unique organic boron-containing pink/red pigment in the pink bands of S. jurassica. We present new geochemical evidence concerning the seasonality and pigmentation of S. jurassica. Seasonal growth cycles are demonstrated by X ray radiography, which shows differences in calcite density, and by varying delta13C composition of the bands. Temperature variation in the bands is difficult to constrain accurately due to conflicting patterns arising from Mg/Ca molar ratios and delta18O data. Fluctuating chlorine levels indicate increased salinity in the white bands, when combined with the isotope data this suggests more suggestive of marine conditions during formation of the white band and a greater freshwater component (lower chlorinity) during pink band precipitation (delta18O). Increased photosynthesis is inferred within the pink bands in comparison to the white, based on delta13C. Pyrolysis Gas Chromatography Mass Spectrometry (Py-GCMS) and Fourier Transform Infrared Spectroscopy (FTIR) show the presence of tetramethyl pyrrole, protein moieties and carboxylic acid groups, suggestive of the presence of the red algal pigment phycoerythrin. This is consistent with the pink colour of S. jurassica. As phycoerythrin is only known to occur in algae and cyanobacteria, and no biomarker evidence of bacteria or sponges was detected we conclude S. jurassica is most likely an alga. Pigment analysis may be a reliable classification method for fossil algae. PMID- 26367118 TI - Mature Erythrocytes of Iguana iguana (Squamata, Iguanidae) Possess Functional Mitochondria. AB - Electron microscopy analyses of Iguana iguana blood preparations revealed the presence of mitochondria within erythrocytes with well-structured cristae. Fluorescence microscopy analyses upon incubation with phalloidin-FITC, Hoechst 33342 and mitochondrial transmembrane potential (Deltapsim)-sensitive probe MitoTracker Red indicated that mitochondria i) widely occur in erythrocytes, ii) are polarized, and iii) seem to be preferentially confined at a "perinuclear" region, as confirmed by electron microscopy. The analysis of NADH-dependent oxygen consumption showed that red blood cells retain the capability to consume oxygen, thereby providing compelling evidence that mitochondria of Iguana erythrocytes are functional and capable to perform oxidative phosphorylation. PMID- 26367119 TI - Transcriptome Characterization of Developing Bean (Phaseolus vulgaris L.) Pods from Two Genotypes with Contrasting Seed Zinc Concentrations. AB - Dry bean (Phaseolus vulgaris L.) seeds are a rich source of dietary zinc, especially for people consuming plant-based diets. Within P. vulgaris there is at least two-fold variation in seed Zn concentration. Genetic studies have revealed seed Zn differences to be controlled by a single gene in two closely related navy bean genotypes, Albion and Voyager. In this study, these two genotypes were grown under controlled fertilization conditions and the Zn concentration of various plant parts was determined. The two genotypes had similar levels of Zn in their leaves and pods but Voyager had 52% more Zn in its seeds than Albion. RNA was sequenced from developing pods of both genotypes. Transcriptome analysis of these genotypes identified 27,198 genes in the developing bean pods, representing 86% of the genes in the P. vulgaris genome (v 1.0 DOE-JGI and USDA-NIFA). Expression was detected in 18,438 genes. A relatively small number of genes (381) were differentially expressed between Albion and Voyager. Differentially expressed genes included three genes potentially involved in Zn transport, including zinc regulated transporter, iron regulated transporter like (ZIP), zinc-induced facilitator (ZIF) and heavy metal associated (HMA) family genes. In addition 12,118 SNPs were identified between the two genotypes. Of the gene families related to Zn and/or Fe transport, eleven genes were found to contain SNPs between Albion and Voyager. PMID- 26367120 TI - Cancer Mortality in People Treated with Antidepressants before Cancer Diagnosis: A Population Based Cohort Study. AB - BACKGROUND: Depression is common after a cancer diagnosis and is associated with an increased mortality, but it is unclear whether depression occurring before the cancer diagnosis affects cancer mortality. We aimed to study cancer mortality of people treated with antidepressants before cancer diagnosis. METHODS AND FINDINGS: We conducted a population based cohort study of all adults diagnosed with cancer between January 2003 and December 2010 in Denmark (N = 201,662). We obtained information on cancer from the Danish Cancer Registry, on the day of death from the Danish Civil Registry, and on redeemed antidepressants from the Danish National Prescription Registry. Current users of antidepressants were defined as those who redeemed the latest prescription of antidepressant 0-4 months before cancer diagnosis (irrespective of earlier prescriptions), and former users as those who redeemed the latest prescription five or more months before cancer diagnosis. We estimated an all-cause one-year mortality rate ratio (MRR) and a conditional five-year MRR for patients who survived the first year after cancer diagnosis and confidence interval (CI) using a Cox proportional hazards regression model. Overall, 33,111 (16.4%) patients redeemed at least one antidepressant prescription in the three years before cancer diagnosis of whom 21,851 (10.8%) were current users at the time of cancer diagnosis. Current antidepressant users had a 32% higher one-year mortality (MRR = 1.32, 95% CI: 1.29-1.35) and a 22% higher conditional five-year mortality (MRR = 1.22, 95% CI: 1.17-1.26) if patients survived the first year after the cancer diagnosis than patients not redeeming antidepressants. The one-year mortality was particularly high for patients who initiated antidepressant treatment within four months before cancer diagnosis (MRR = 1.54, 95% CI: 1.47-1.61). Former users had no increased cancer mortality. CONCLUSIONS: Initiation of antidepressive treatment prior to cancer diagnosis is common and is associated with an increased mortality. PMID- 26367121 TI - Acetyl CoA Carboxylase 2 Is Dispensable for CD8+ T Cell Responses. AB - Differentiation of T cells is closely associated with dynamic changes in nutrient and energy metabolism. However, the extent to which specific metabolic pathways and molecular components are determinative of CD8+ T cell fate remains unclear. It has been previously established in various tissues that acetyl CoA carboxylase 2 (ACC2) regulates fatty acid oxidation (FAO) by inhibiting carnitine palmitoyltransferase 1 (CPT1), a rate-limiting enzyme of FAO in mitochondria. Here, we explore the cell-intrinsic role of ACC2 in T cell immunity in response to infections. We report here that ACC2 deficiency results in a marginal increase of cellular FAO in CD8+ T cells, but does not appear to influence antigen specific effector and memory CD8+ T cell responses during infection with listeria or lymphocytic choriomeningitis virus. These results suggest that ACC2 is dispensable for CD8+ T cell responses. PMID- 26367122 TI - Face Orientation and Motion Differently Affect the Deployment of Visual Attention in Newborns and 4-Month-Old Infants. AB - Orienting visual attention allows us to properly select relevant visual information from a noisy environment. Despite extensive investigation of the orienting of visual attention in infancy, it is unknown whether and how stimulus characteristics modulate the deployment of attention from birth to 4 months of age, a period in which the efficiency in orienting of attention improves dramatically. The aim of the present study was to compare 4-month-old infants' and newborns' ability to orient attention from central to peripheral stimuli that have the same or different attributes. In Experiment 1, all the stimuli were dynamic and the only attribute of the central and peripheral stimuli to be manipulated was face orientation. In Experiment 2, both face orientation and motion of the central and peripheral stimuli were contrasted. The number of valid trials and saccadic latency were measured at both ages. Our results demonstrated that the deployment of attention is mainly influenced by motion at birth, while it is also influenced by face orientation at 4-month of age. These findings provide insight into the development of the orienting visual attention in the first few months of life and suggest that maturation may be not the only factor that determines the developmental change in orienting visual attention from birth to 4 months. PMID- 26367123 TI - The Invasive American Weed Parthenium hysterophorus Can Negatively Impact Malaria Control in Africa. AB - The direct negative effects of invasive plant species on agriculture and biodiversity are well known, but their indirect effects on human health, and particularly their interactions with disease-transmitting vectors, remains poorly explored. This study sought to investigate the impact of the invasive Neotropical weed Parthenium hysterophorus and its toxins on the survival and energy reserves of the malaria vector Anopheles gambiae. In this study, we compared the fitness of An. gambiae fed on three differentially attractive mosquito host plants and their major toxins; the highly aggressive invasive Neotropical weed Parthenium hysterophorus (Asteraceae) in East Africa and two other adapted weeds, Ricinus communis (Euphorbiaceae) and Bidens pilosa (Asteraceae). Our results showed that female An. gambiae fitness varied with host plants as females survived better and accumulated substantial energy reserves when fed on P. hysterophorus and R. communis compared to B. pilosa. Females tolerated parthenin and 1-phenylhepta-1, 3, 5-triyne, the toxins produced by P. hysterophorus and B. pilosa, respectively, but not ricinine produced by R. communis. Given that invasive plants like P. hysterophorus can suppress or even replace less competitive species that might be less suitable host-plants for arthropod disease vectors, the spread of invasive plants could lead to higher disease transmission. Parthenium hysterophorus represents a possible indirect effect of invasive plants on human health, which underpins the need to include an additional health dimension in risk-analysis modelling for invasive plants. PMID- 26367125 TI - High-fidelity AFM scanning stage based on multilayer ceramic capacitors. AB - A kind of multilayer ceramic capacitors (MLCCs) has been verified to have good micro-actuating properties, thus making them good candidates for nano positioning. In this paper, we successfully employed the MLCCs as lateral scanners for a tripod scanning stage. The MLCC-based lateral scanners display hysteresis under 1.5% and a nonlinearity less than 2% even with the simplest open loop voltage drive. The developed scanning stage was integrated into a commercial AFM to evaluate its imaging performance. Experimental results showed that sample images with high fidelities were obtained. SCANNING 38:184-190, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26367126 TI - Upward Altitudinal Shifts in Habitat Suitability of Mountain Vipers since the Last Glacial Maximum. AB - We determined the effects of past and future climate changes on the distribution of the Montivipera raddei species complex (MRC) that contains rare and endangered viper species limited to Iran, Turkey and Armenia. We also investigated the current distribution of MRC to locate unidentified isolated populations as well as to evaluate the effectiveness of the current network of protected areas for their conservation. Present distribution of MRC was modeled based on ecological variables and model performance was evaluated by field visits. Some individuals at the newly identified populations showed uncommon morphological characteristics. The distribution map of MRC derived through modeling was then compared with the distribution of protected areas in the region. We estimated the effectiveness of the current protected area network to be 10%, which would be sufficient for conserving this group of species, provided adequate management policies and practices are employed. We further modeled the distribution of MRC in the past (21,000 years ago) and under two scenarios in the future (to 2070). These models indicated that climatic changes probably have been responsible for an upward shift in suitable habitats of MRC since the Last Glacial Maximum, leading to isolation of allopatric populations. Distribution will probably become much more restricted in the future as a result of the current rate of global warming. We conclude that climate change most likely played a major role in determining the distribution pattern of MRC, restricting allopatric populations to mountaintops due to habitat alterations. This long-term isolation has facilitated unique local adaptations among MRC populations, which requires further investigation. The suitable habitat patches identified through modeling constitute optimized solutions for inclusion in the network of protected areas in the region. PMID- 26367127 TI - Missing wedge computed tomography by iterative algorithm DIRECTT. AB - A strategy to mitigate typical reconstruction artefacts in missing wedge computed tomography is presented. These artefacts appear as elongations of reconstructed details along the mean direction (i.e. the symmetry centre of the projections). Although absent in standard computed tomography applications, they are most prominent in advanced electron tomography and also in special topics of X-ray and neutron tomography under restricted geometric boundary conditions. We investigate the performance of the DIRECTT (Direct Iterative Reconstruction of Computed Tomography Trajectories) algorithm to reduce the directional artefacts in standard procedures. In order to be sensitive to the anisotropic nature of missing wedge artefacts, we investigate isotropic substructures of metal foam as well as circular disc models. Comparison is drawn to filtered backprojection and algebraic techniques. Reference is made to reconstructions of complete data sets. For the purpose of assessing the reconstruction quality, Fourier transforms are employed to visualize the missing wedge directly. Deficient reconstructions of disc models are evaluated by a length-weighted kernel density estimation, which yields the probabilities of boundary orientations. The DIRECTT results are assessed at different signal-to-noise ratios by means of local and integral evaluation parameters. PMID- 26367124 TI - The Toll-Like Receptor 5 Agonist Entolimod Mitigates Lethal Acute Radiation Syndrome in Non-Human Primates. AB - There are currently no approved medical radiation countermeasures (MRC) to reduce the lethality of high-dose total body ionizing irradiation expected in nuclear emergencies. An ideal MRC would be effective even when administered well after radiation exposure and would counteract the effects of irradiation on the hematopoietic system and gastrointestinal tract that contribute to its lethality. Entolimod is a Toll-like receptor 5 agonist with demonstrated radioprotective/mitigative activity in rodents and radioprotective activity in non-human primates. Here, we report data from several exploratory studies conducted in lethally irradiated non-human primates (rhesus macaques) treated with a single intramuscular injection of entolimod (in the absence of intensive individualized supportive care) administered in a mitigative regimen, 1-48 hours after irradiation. Following exposure to LD50-70/40 of radiation, injection of efficacious doses of entolimod administered as late as 25 hours thereafter reduced the risk of mortality 2-3-fold, providing a statistically significant (P<0.01) absolute survival advantage of 40-60% compared to vehicle treatment. Similar magnitude of survival improvement was also achieved with drug delivered 48 hours after irradiation. Improved survival was accompanied by predominantly significant (P<0.05) effects of entolimod administration on accelerated morphological recovery of hematopoietic and immune system organs, decreased severity and duration of thrombocytopenia, anemia and neutropenia, and increased clonogenic potential of the bone marrow compared to control irradiated animals. Entolimod treatment also led to reduced apoptosis and accelerated crypt regeneration in the gastrointestinal tract. Together, these data indicate that entolimod is a highly promising potential life-saving treatment for victims of radiation disasters. PMID- 26367129 TI - Protocol registration and selective outcome reporting in recent psychiatry trials: new antidepressants and cognitive behavioural therapies. AB - OBJECTIVE: The selective reporting of favorable outcomes has a serious influence on our evidence base. However, this problem has not yet been systematically investigated in the field of psychiatry. Our study aimed to evaluate registration and outcome reporting in randomized controlled trials (RCTs) of standard treatments for depression: cognitive behavioural therapy (CBT) or new-generation antidepressants (ADs). METHOD: We searched for reports of RCTs examining the efficacy of CBT or AD for depression that were published between 2011 and 2013. We then compared their primary outcomes in the trial registries and those in publications. RESULTS: We identified 170 trials. Among them, 92 trials (54.1%) were registered, 43 trials (25.3%) were properly registered, and only 32 (18.8%) trials were both properly registered and reported (the primary outcomes as recorded in the registries were reported in publications). There was no statistically significant difference in the proportions of properly registered and reported trials for CBT or AD (relative risk: 0.51, 95% CI: 0.25-1.03). High impact factor journals, commercial funding, publication of protocol, and relatively large sample size were significant predictors of proper registration and reporting. CONCLUSION: The prevalence of proper registration and reporting is still very low in depression trials. PMID- 26367128 TI - Antigenicity, Immunogenicity and Protective Efficacy of Three Proteins Expressed in the Promastigote and Amastigote Stages of Leishmania infantum against Visceral Leishmaniasis. AB - In the present study, two Leishmania infantum hypothetical proteins present in the amastigote stage, LiHyp1 and LiHyp6, were combined with a promastigote protein, IgE-dependent histamine-releasing factor (HRF); to compose a polyproteins vaccine to be evaluated against L. infantum infection. Also, the antigenicity of the three proteins was analyzed, and their use for the serodiagnosis of canine visceral leishmaniasis (CVL) was evaluated. The LiHyp1, LiHyp6, and HRF DNA coding sequences were cloned in prokaryotic expression vectors and the recombinant proteins were purified. When employed in ELISA assays, all proteins were recognized by sera from visceral leishmaniasis (VL) dogs, and presented no cross-reactivity with either sera from dogs vaccinated with a Brazilian commercial vaccine, or sera of Trypanosoma cruzi-infected or Ehrlichia canis-infected animals. In addition, the antigens were not recognized by antibodies from non-infected animals living in endemic or non-endemic areas for leishmaniasis. The immunogenicity and protective efficacy of the three proteins administered in the presence of saponin, individually or in combination (composing a polyproteins vaccine), were evaluated in a VL murine model: BALB/c mice infected with L. infantum. Spleen cells from mice inoculated with the individual proteins or with the polyproteins vaccine plus saponin showed a protein-specific production of IFN-gamma, IL-12, and GM-CSF after an in vitro stimulation, which was maintained after infection. These animals presented significant reductions in the parasite burden in different evaluated organs, when compared to mice inoculated with saline or saponin. The decrease in parasite burden was associated with an IL-12-dependent production of IFN-gamma against parasite total extracts (produced mainly by CD4+ T cells), correlated to the induction of parasite proteins-driven NO production. Mice inoculated with the recombinant protein-based vaccines showed also high levels of parasite-specific IgG2a antibodies. The polyproteins vaccine administration induced a more pronounced Th1 response before and after challenge infection than individual vaccines, which was correlated to a higher control of parasite dissemination to internal organs. PMID- 26367130 TI - Interleukin-17A and Neutrophils in a Murine Model of Bird-Related Hypersensitivity Pneumonitis. AB - Hypersensitivity pneumonitis (HP) is an immune mediated lung disease induced by the repeated inhalation of a wide variety of antigens. Bird-related hypersensitivity pneumonitis (BRHP) is one of the most common forms of HP in human and results from the inhalation of avian antigens. The findings of a recent clinical analysis suggest that in addition to Th1 factors, the levels of interleukin(IL)-17 and IL-17-associated transcripts are increased in the setting of HP, and that both IL-17A and neutrophils are crucial for the development of pulmonary inflammation in murine models of HP. Our objectives were to investigate the roles of IL-17A and neutrophils in granuloma-forming inflammation in an acute HP model. We developed a mouse model of acute BRHP using pigeon dropping extract. We evaluated the process of granuloma formation and the roles of both IL-17A and neutrophils in a model. We found that the neutralization of IL-17A by the antibody attenuated granuloma formation and the recruitment of neutrophils, and also decreased the expression level of chemokine(C-X-C motif) ligand 5 (CXCL5) in the acute HP model. We confirmed that most of the neutrophils in the acute HP model exhibited immunoreactivity to the anti-IL-17 antibody. We have identified the central roles of both IL-17A and neutrophils in the pathogenesis of granuloma formation in acute HP. We have also assumed that neutrophils are an important source of IL-17A in an acute HP model, and that the IL-17A-CXCL5 pathway may be responsible for the recruitment of neutrophils. PMID- 26367132 TI - Sequencing, biochemical characterization, crystal structure and molecular dynamics of cellobiohydrolase Cel7A from Geotrichum candidum 3C. AB - The ascomycete Geotrichum candidum is a versatile and efficient decay fungus that is involved, for example, in biodeterioration of compact discs; notably, the 3C strain was previously shown to degrade filter paper and cotton more efficiently than several industrial enzyme preparations. Glycoside hydrolase (GH) family 7 cellobiohydrolases (CBHs) are the primary constituents of industrial cellulase cocktails employed in biomass conversion, and feature tunnel-enclosed active sites that enable processive hydrolytic cleavage of cellulose chains. Understanding the structure-function relationships defining the activity and stability of GH7 CBHs is thus of keen interest. Accordingly, we report the comprehensive characterization of the GH7 CBH secreted by G. candidum (GcaCel7A). The bimodular cellulase consists of a family 1 cellulose-binding module (CBM) and linker connected to a GH7 catalytic domain that shares 64% sequence identity with the archetypal industrial GH7 CBH of Hypocrea jecorina (HjeCel7A). GcaCel7A shows activity on Avicel cellulose similar to HjeCel7A, with less product inhibition, but has a lower temperature optimum (50 degrees C versus 60-65 degrees C, respectively). Five crystal structures, with and without bound thio oligosaccharides, show conformational diversity of tunnel-enclosing loops, including a form with partial tunnel collapse at subsite -4 not reported previously in GH7. Also, the first O-glycosylation site in a GH7 crystal structure is reported--on a loop where the glycan probably influences loop contacts across the active site and interactions with the cellulose surface. The GcaCel7A structures indicate higher loop flexibility than HjeCel7A, in accordance with sequence modifications. However, GcaCel7A retains small fluctuations in molecular simulations, suggesting high processivity and low endo-initiation probability, similar to HjeCel7A. DATABASE: Structural data are available in the Protein Data Bank under the accession numbers 5AMP, 4ZZV, 4ZZW, 4ZZT, and 4ZZU. The Geotrichum candidum GH family 7 cellobiohydrolase nucleotide sequence is available in GenBank under accession number KJ958925. ENZYMES: Glycoside hydrolase family 7 reducing end acting cellobiohydrolase. PMID- 26367131 TI - The NLRP3 Inflammasome and IL-1beta Accelerate Immunologically Mediated Pathology in Experimental Viral Fulminant Hepatitis. AB - Viral fulminant hepatitis (FH) is a severe disease with high mortality resulting from excessive inflammation in the infected liver. Clinical interventions have been inefficient due to the lack of knowledge for inflammatory pathogenesis in the virus-infected liver. We show that wild-type mice infected with murine hepatitis virus strain-3 (MHV-3), a model for viral FH, manifest with severe disease and high mortality in association with a significant elevation in IL 1beta expression in the serum and liver. Whereas, the viral infection in IL-1beta receptor-I deficient (IL-1R1-/-) or IL-1R antagonist (IL-1Ra) treated mice, show reductions in virus replication, disease progress and mortality. IL-1R1 deficiency appears to debilitate the virus-induced fibrinogen-like protein-2 (FGL2) production in macrophages and CD45+Gr-1high neutrophil infiltration in the liver. The quick release of reactive oxygen species (ROS) by the infected macrophages suggests a plausible viral initiation of NLRP3 inflammasome activation. Further experiments show that mice deficient of p47phox, a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit that controls acute ROS production, present with reductions in NLRP3 inflammasome activation and subsequent IL-1beta secretion during viral infection, which appears to be responsible for acquiring resilience to viral FH. Moreover, viral infected animals in deficiencies of NLRP3 and Caspase-1, two essential components of the inflammasome complex, also have reduced IL-1beta induction along with ameliorated hepatitis. Our results demonstrate that the ROS/NLRP3/IL-1beta axis institutes an essential signaling pathway, which is over activated and directly causes the severe liver disease during viral infection, which sheds light on development of efficient treatments for human viral FH and other severe inflammatory diseases. PMID- 26367133 TI - Cognitive Impairment in Chinese Patients with Sporadic Amyotrophic Lateral Sclerosis. AB - BACKGROUND: It has reached a consensus that patients with amyotrophic lateral sclerosis (ALS) could display cognitive impairment characterized by executive dysfunction or even dementia, but cognitive spectrum of Chinese patients with ALS still waits to be documented. METHODS: A total of 106 incident patients with sporadic ALS were enrolled and comprehensive neuropsychological tests covering memory, executive function, attention, language, and visuospatial function were administered to them. Neuropsychological performances of 76 age- and education- matched healthy controls were used for the purpose of classification and comparison. RESULTS: 106 patients were categorized into 4 subtypes:84 (79.2%) ALS with normal cognition (ALS-NC), 12 (11.3%) ALS with executive cognitive impairment (ALS-ECI), 5 (4.7%) ALS with non-executive cognitive impairment (ALS NECI), and 5 (4.7%) ALS with frontotemporal lobe degeneration (ALS-FTLD). Under the same criteria, 2 (2.6%) and 1 (1.3%) healthy controls were diagnosed as ECI and NECI, respectively. The proportion of ECI was significantly higher in non demented ALS than that in healthy controls, but it was not for NECI. Patients with ALS-FTLD had significantly severer bulbar function and older age than those with ALS-NC. CONCLUSION: Comorbid FTLD occurred in around 5% of Chinese sporadic ALS cases. Different genetic background and unique age distribution of Chinese ALS patients might be the reasons for the relatively low rate of comorbid FTLD. Cognitive dysfunction, predominant but not exclusive in executive area, was present in around 16% of non-demented ALS patients. PMID- 26367134 TI - Recyclable Ligands for the Non-Enzymatic Dynamic Kinetic Resolution of Challenging alpha-Amino Acids. AB - Structurally simple and inexpensive chiral tridentate ligands were employed for substantially advancing the purely chemical dynamic kinetic resolution (DKR) of unprotected racemic tailor-made alpha-amino acids (TM-alpha-AAs), enabling the first DKR of TM-alpha-AAs bearing tertiary alkyl chains as well as multiple unprotected functional groups. Owing to the operationally convenient conditions, virtually complete stereoselectivity, and full recyclability of the source of chirality, this method should find wide applications for the preparation of TM alpha-AAs, especially on large scale. PMID- 26367136 TI - Direct Observation of Kinetic Pathways of Biomolecular Recognition. AB - The pathways of molecular recognition, which is a central event in all biological processes, belong to the most important subjects of contemporary research in biomolecular science. By using fluorescence spectroscopy in a microfluidics channel, it can be determined that molecular recognition of alpha-chymotrypsin in hydrous surroundings at two different pH values (3.6 and 6.3) follows two distinctly different pathways. Whereas one corroborates an induced-fit model (pH 3.6), the other one (pH 6.3) is consistent with the selected-fit model of biomolecular recognition. The role of massive structural perturbations of differential recognition pathways could be ruled out by earlier XRD studies, rather was consistent with the femtosecond-resolved observation of dynamic flexibility of the protein at different pH values. At low concentrations of ligands, the selected-fit model dominates, whereas increasing the ligand concentration leads to the induced-fit model. From molecular modelling and experimental results, the timescale associated with the conformational flexibility of the protein plays a key role in the selection of a pathway in biomolecular recognition. PMID- 26367138 TI - Design, Virtual Screening, and Synthesis of Antagonists of alphaIIbbeta3 as Antiplatelet Agents. AB - This article describes design, virtual screening, synthesis, and biological tests of novel alphaIIbbeta3 antagonists, which inhibit platelet aggregation. Two types of alphaIIbbeta3 antagonists were developed: those binding either closed or open form of the protein. At the first step, available experimental data were used to build QSAR models and ligand- and structure-based pharmacophore models and to select the most appropriate tool for ligand-to-protein docking. Virtual screening of publicly available databases (BioinfoDB, ZINC, Enamine data sets) with developed models resulted in no hits. Therefore, small focused libraries for two types of ligands were prepared on the basis of pharmacophore models. Their screening resulted in four potential ligands for open form of alphaIIbbeta3 and four ligands for its closed form followed by their synthesis and in vitro tests. Experimental measurements of affinity for alphaIIbbeta3 and ability to inhibit ADP-induced platelet aggregation (IC50) showed that two designed ligands for the open form 4c and 4d (IC50 = 6.2 nM and 25 nM, respectively) and one for the closed form 12b (IC50 = 11 nM) were more potent than commercial antithrombotic Tirofiban (IC50 = 32 nM). PMID- 26367139 TI - Why do we lose protected areas? Factors influencing protected area downgrading, downsizing and degazettement in the tropics and subtropics. AB - Protected areas (PAs) are an essential tool for the conservation of biodiversity globally. Previous studies have focussed on the effectiveness of PAs and the design of optimal PA networks. However, not all PAs remain intact permanently; many PAs undergo downgrading, downsizing and/or degazettement (PADDD), a fact largely ignored until recently. The drivers of enacted PADDD events and the factors influencing its spatial occurrence are poorly understood, potentially undermining the efficacy of PAs and PA networks. Here we examine the spatial relationship between PADDD and economic, demographic and structural variables, using a 110-year data set of 342 enacted PADDD events across 44 countries in the tropics and subtropics. We find that the probability of an enacted PADDD event increases with the size of the PA and through a synergistic interaction between PA size and local population densities. Our results are robust to the under reporting of enacted PADDD events that occur among smaller PAs and in regions with lower population density. We find an economic motive for PADDD events, given that the opportunity costs associated with larger PAs are higher, on average, than smaller PAs. Our findings suggest a need for conservation practitioners to better consider PA characteristics, as well as the social, economic and political context in which PAs are situated, to aid the creation of more efficient and sustainable PA networks. In particular, the dynamics of enacted PADDD events highlight the need to explicitly consider PA robustness as a core component of systematic conservation planning for PA networks. PMID- 26367137 TI - Characterization of In Vitro Engineered Human Adipose Tissues: Relevant Adipokine Secretion and Impact of TNF-alpha. AB - Representative modelling of human adipose tissue functions is central to metabolic research. Tridimensional models able to recreate human adipogenesis in a physiological tissue-like context in vitro are still scarce. We describe the engineering of white adipose tissues reconstructed from their cultured adipose derived stromal precursor cells. We hypothesize that these reconstructed tissues can recapitulate key functions of AT under basal and pro-inflammatory conditions. These tissues, featuring human adipocytes surrounded by stroma, were stable and metabolically active in long-term cultures (at least 11 weeks). Secretion of major adipokines and growth factors by the reconstructed tissues was determined and compared to media conditioned by human native fat explants. Interestingly, the secretory profiles of the reconstructed adipose tissues indicated an abundant production of leptin, PAI-1 and angiopoietin-1 proteins, while higher HGF levels were detected for the human fat explants. We next demonstrated the responsiveness of the tissues to the pro-inflammatory stimulus TNF-alpha, as reflected by modulation of MCP-1, NGF and HGF secretion, while VEGF and leptin protein expression did not vary. TNF-alpha exposure induced changes in gene expression for adipocyte metabolism-associated mRNAs such as SLC2A4, FASN and LIPE, as well as for genes implicated in NF-kappaB activation. Finally, this model was customized to feature adipocytes representative of progressive stages of differentiation, thereby allowing investigations using newly differentiated or more mature adipocytes. In conclusion, we produced tridimensional tissues engineered in vitro that are able to recapitulate key characteristics of subcutaneous white adipose tissue. These tissues are produced from human cells and their neo-synthesized matrix elements without exogenous or synthetic biomaterials. Therefore, they represent unique tools to investigate the effects of pharmacologically active products on human stromal cells, extracellular matrix and differentiated adipocytes, in addition to compounds modulating adipogenesis from precursor cells. PMID- 26367140 TI - Synthesis and Applications of Boronic Acid-Containing Polymers: From Materials to Medicine. PMID- 26367141 TI - Longer-Term Follow-Up of Kenyan Men Circumcised Using the ShangRing Device. AB - OBJECTIVES: To ascertain clinical sequelae, client satisfaction and sexual behavior 2+ years after male circumcision using the ShangRing device. METHODS: We enrolled 199 men from the Kenya sites (Homa Bay district) participating in a 2012 study of the ShangRing device used in routine male circumcision services (N = 552). We enrolled men who had had the ShangRing placed successfully, and over sampled men who had had an adverse event and/or were HIV-positive during the field study. In the present study, each participant was examined and interviewed by a study clinician, and penile photographs were taken to document longer-term cosmetic results and any abnormal findings. RESULTS: 194 men were included in the analysis. The mean and median times between circumcision and the longer-term follow-up visit in this study were 31.8 and 32 months, respectively. Four men (2.1%) had signs/symptoms of a sexually transmitted infection (STI). Virtually all (99.5%) of the men were very satisfied with the appearance of their circumcised penis, and all would recommend a ShangRing circumcision to friends or family members. The most prevalent reported advantage of the circumcision was the ease of bathing and enhanced cleanliness of the penis (75.8%). 94.3% of the men did not cite a single negative feature of their circumcision. 87.5% of men reported more sexual pleasure post-MC, the most common reason being more prolonged intercourse. The majority of men (52.6%) reported one sexual partner post-MC, but more than a quarter of the men (28.1%) reported an increased number of partners post-MC. Less than half of the men (44.3%) reported using condoms half of the time or more, but the great majority of condom users stated that condom use was much easier post-MC, and 76.9% of users said they used condoms more after circumcision than before. CONCLUSIONS: This study supports the safety and acceptability of ShangRing male circumcision during 2-3 years of follow-up. It should allay worries that the ShangRing procedure could lead to delayed complications later than the observation period of most clinical studies. TRIAL REGISTRATION: ClinicalTrials.gov NCT01567436. PMID- 26367143 TI - [Management of Idiopathic Frozen Shoulder - Prospective Evaluation of Mobilisation under Anaesthesia and an Additional Subacromial Cortisone Injection]. AB - BACKGROUND: Management of primary frozen shoulder is still controversial. Many authors tend to treat patients with an arthroscopic release, if conservative therapy fails. We aimed to demonstrate the efficiency of manipulation under anaesthesia (MUA) in patients with primary frozen shoulder and to contrast the outcome of single MUA with the results of MUA with an additional subacromial injection of cortisone. MATERIAL AND METHODS: A prospective trial with a 1-year follow-up was performed. Between 2008 and 2011 30 patients with idiopathic frozen shoulder underwent MUA, 15 of them received an additional injection of triamcinolone and bupivacain. Thereafter all patients underwent a standardised physiotherapy treatment regime for three months. The patients were assessed for pain, function, range of motion and the Constant-Murley score (CMS) before MUA as well as 1, 6 and 12 months after the intervention. RESULTS: Range of motion increased significantly (p < 0.05) in all planes at every point of follow-up. Preinterventional abduction improved from 65.80 degrees +/- 13.25 to 145.40 degrees +/- 18.50, preinterventional forward flexion from 90.20 degrees +/- 18.98 to 155.60 degrees +/- 13.51 at 1 month after MUA. At this point 80 % of patients had returned to work, 66.7 % were free of pain. One year after MUA abduction was improved to 173.07 degrees +/- 6.03, forward flexion to 175.47 degrees +/- 4.03. The CMS rose significantly (p < 0.05) from 24.53 +/- 9.28/100 to 73.97 +/- 10.77/100 after 1 month and up to 86.30 +/- 5.62/100 after 1 year. Range of motion and function as described for a healthy shoulder were recognised in every patient during 1 year. However additional subacromial injections of triamcinolone and bupivacain did not lead to a significant improvement. There were no complications reported. CONCLUSION: This study demonstrates that MUA is a safe and effective tool in the management of idiopathic frozen shoulder, if conservative therapy fails. An additional subacromial injection of cortisone however does not generate a significant improvement. PMID- 26367142 TI - A Proteomic Analysis of the Body Wall, Digestive Tract, and Reproductive Tract of Brugia malayi. AB - Filarial worms are parasitic nematodes that cause devastating diseases such as lymphatic filariasis (LF) and onchocerciasis. Filariae are nematodes with complex anatomy including fully developed digestive tracts and reproductive organs. To better understand the basic biology of filarial parasites and to provide insights into drug targets and vaccine design, we conducted a proteomic analysis of different anatomic fractions of Brugia malayi, a causative agent of LF. Approximately 500 adult female B. malayi worms were dissected, and three anatomical fractions (body wall, digestive tract, and reproductive tract) were obtained. Proteins from each anatomical fraction were extracted, desalted, trypsinized, and analyzed by microcapillary reverse-phase liquid chromatography tandem-mass spectrometry. In total, we identified 4,785 B. malayi proteins. While 1,894 were identified in all three anatomic fractions, 396 were positively identified only within the digestive tract, 114 only within the body wall, and 1,011 only within the reproductive tract. Gene set enrichment analysis revealed a bias for transporters to be present within the digestive tract, suggesting that the intestine of adult filariae is functional and important for nutrient uptake or waste removal. As expected, the body wall exhibited increased frequencies of cytoskeletal proteins, and the reproductive tract had increased frequencies of proteins involved in nuclear regulation and transcription. In assessing for possible vaccine candidates, we focused on proteins sequestered within the digestive tract, as these could possibly represent "hidden antigens" with low risk of prior allergic sensitization. We identified 106 proteins that are enriched in the digestive tract and are predicted to localize to the surface of cells in the the digestive tract. It is possible that some of these proteins are on the luminal surface and may be accessible by antibodies ingested by the worm. A subset of 27 of these proteins appear especially promising vaccine candidates as they contain significant non-cytoplasmic domains, only 1-2 transmembrane domains, and a high degree of homology to W. bancrofti and/or O. volvulus. PMID- 26367145 TI - [Bearing selection in total hip arthroplasty]. AB - Different bearing materials are available in total hip arthroplasty and it's the surgeon who has the choice between hard-on-soft, hard-on-hard and alternative materials. Ideally, the material selection should rely on evidence-based data regarding the wear performance, the incidence of revision surgery and other potential bearing-associated risk factors for the corresponding combinations of materials in the individual patient. While there are high-quality studies available for some materials, adequate data is lacking for other materials. Therefore, the current article aims to provide bearing selection criteria for the surgeon and to review the current literature regarding different combinations of bearing materials in total hip arthroplasty. PMID- 26367144 TI - [Quality of Outcome after Primary Total Hip Replacement at a Maximum Care Hospital in Relation to Preoperative Influencing Factors]. AB - BACKGROUND: As the need for joint replacements will continue to rise, the outcome of primary total hip replacement (THR) must be improved and stabilised at a high level. In this study, we investigated whether pre-operative risk factors, such as gender, age and body weight at the time of the surgery or a restricted physical status (ASA-Status > 2 or Kellgren and Lawrence grade > 2) have a negative influence on the post-operative results or on patient satisfaction. MATERIAL AND METHODS: Retrospective data collection and a prospective interview were performed with 486 patients who underwent primary total hip replacement between January 2007 and December 2010 in our hospital. The patients' satisfaction and quality of life were surveyed with the WOMAC-Score, SF-36 and EuroQol-5. Differences between more than two independent spot tests were tested with the non-parametric Kruskal Wallis test. Differences between two independent spot tests were tested with the non-parametric Mann-Whitney U test. The frequencies were reported and odds ratios calculated. The confidence interval was set at 95 %. The level of significance was p < 0.05. RESULTS: The average WOMAC-Score was 77.1 and the total score of the SF-36 was 66.9 points. The patients declared an average EuroQol Index of 0.81. Our data show that the patients' gender did not influence the duration of surgery or the scores. However, female patients tended to exhibit more postoperative complications. However, increased patient age at the time of surgery was associated with an increased OR for duration of surgery, length of stay and risk of complications. Patients who had a normal body weight at time of the surgery showed better peri- and post-operative results. We showed that the preoperative estimated Kellgren and Lawrence grade had a significant influence on the duration of surgery. The ASA classification influenced the duration of surgery as well the length of stay and the rate of complications. CONCLUSION: The quality of results after primary THR depends on preoperative factors. Existing comorbidities have a significant influence on the duration of surgery and therefore on the perioperative rate of complications and the postoperative outcome. Despite improvements in the functional and subjective outcome after primary THR, an adverse preoperative symptomatic status is associated with less favourable postoperative results. PMID- 26367147 TI - Extraction of all propagation constants in a specified region from the transcendental equation of a dispersion relation using the Sakurai-Sugiura projection method. AB - A transcendental equation occurs when we compute the dispersion relations of an electromagnetic waveguide, such as a planar multilayer waveguide. Without an initial guess, the Sakurai-Sugiura projection method (SSM) can obtain solutions to the transcendental equation in a region bounded by a contour integral path in the complex plane. In this paper, a criterion employing the condition number of eigenvalues as a simple index to distinguish physical solutions from spurious ones in the SSM is presented, and a transcendental equation of a multilayer waveguide obtained by the transfer matrix method is solved by the SSM. Numerical results show the usefulness of the index and good agreement with the results of the argument principle method and Newton's method. PMID- 26367146 TI - Correction: High Resolution Crystal Structure of Human beta-Glucuronidase Reveals Structural Basis of Lysosome Targeting. PMID- 26367148 TI - Adequacy of the rigorous coupled-wave approach for thin-film silicon solar cells with periodically corrugated metallic backreflectors: spectral analysis. AB - The rigorous coupled-wave approach (RCWA) is extensively used to compute optical absorption and photon absorption in thin-film photovoltaic solar cells backed by 1D metallic gratings when the wave vector of the incident light lies wholly in the grating plane. The RCWA algorithm converges rapidly for incident s-polarized light over the entire 400-1100 nm solar spectrum. It also performs well for incident p-polarized light in the 400-650 nm spectral regime, but even with a large number of Floquet harmonics in the solution, the total reflectance is underestimated in the 650-1100 nm spectral regime. Despite that shortcoming, the RCWA underestimates the solar-spectrum-integrated photon absorption rate only by 5%-10% for p-polarized light. As sunlight is almost unpolarized, the RCWA should be considered adequate to design thin-film silicon solar cells with periodically corrugated metallic backreflectors. PMID- 26367149 TI - Effect of the imaginary part of the refractive index on light scattering by spheres. AB - For spheres of arbitrary radius R and complex index of refraction n+ikappa, we identify a new parameter that indicates when the imaginary part kappa seriously affects the scattering by a sphere. The parameter is kappakR, where k is the wave vector magnitude, such that when kappakR grows larger than one, the scattering is affected and, when kappakR>3, the effects saturate. The effects are uncovered and demonstrated with Q-space analysis. The physical basis for kappakR lies in the fact that it is the ratio of the radius to the optical skin depth. PMID- 26367150 TI - Angular spectral framework to test full corrections of paraxial solutions. AB - Different correction methods for paraxial solutions have been used when such solutions extend out of the paraxial regime. The authors have used correction methods guided by either their experience or some educated hypothesis pertinent to the particular problem that they were tackling. This article provides a framework so as to classify full wave correction schemes. Thus, for a given solution of the paraxial wave equation, we can select the best correction scheme of those available. Some common correction methods are considered and evaluated under the proposed scope. Another remarkable contribution is obtained by giving the necessary conditions that two solutions of the Helmholtz equation must accomplish to accept a common solution of the parabolic wave equation as a paraxial approximation of both solutions. PMID- 26367151 TI - Computational method for transmission eigenvalues for a spherically stratified medium. AB - We consider a computational method for the interior transmission eigenvalue problem that arises in acoustic and electromagnetic scattering. The transmission eigenvalues contain useful information about some physical properties, such as the index of refraction. Instead of the existence and estimation of the spectral property of the transmission eigenvalues, we focus on the numerical calculation, especially for spherically stratified media in R3. Due to the nonlinearity and the special structure of the interior transmission eigenvalue problem, there are not many numerical methods to date. First, we reduce the problem into a second-order ordinary differential equation. Then, we apply the Hermite finite element to the weak formulation of the equation. With proper rewriting of the matrix-vector form, we change the original nonlinear eigenvalue problem into a quadratic eigenvalue problem, which can be written as a linear system and solved by the eigs function in MATLAB. This numerical method is fast, effective, and can calculate as many transmission eigenvalues as needed at a time. PMID- 26367152 TI - Bit error rate of focused Gaussian beams in weak oceanic turbulence: comment. AB - Recent calculations [J. Opt. Soc. Am. A31, 1963 (2014)JOAOD60740 323210.1364/JOSAA.31.001963] of the scintillation index of focused beams did not take into account the second order of the perturbation theory, and therefore led the author to erroneous conclusions regarding dependence of the scintillation index for the focused beams on the aperture size. The log-normal intensity probability distribution used for the Bit Error Rate calculations in [J. Opt. Soc. Am. A31, 1963 (2014)JOAOD60740-323210.1364/JOSAA.31.001963] is also invalid for the wide focused beams. As a result, most of the conclusions of [J. Opt. Soc. Am. A31, 1963 (2014)JOAOD60740-323210.1364/JOSAA.31.001963] are incorrect. PMID- 26367153 TI - High-resolution interference with programmable classical incoherent light. AB - A scheme of high-resolution interference with classical incoherent light is proposed. In this scheme, the classical incoherent light is programmable in the amplitude distribution and wavefront, and with the programmable classical incoherent light we improve the resolution of the interference pattern by a factor of 2 compared with the scheme by Erkmen [J. Opt. Soc. Am. A29, 782 (2012)JOAOD60740-323210.1364/JOSAA.29.000782]. Compared with other schemes for observing interference patterns, only single-pixel detection is needed in our proposal. Moreover, the high-resolution interference pattern can be inverted to obtain an image with better resolution compared with that of the scheme proposed by Erkmen. Furthermore, this scheme of high-resolution interference is verified in detail by theoretical analysis and numerical simulations. PMID- 26367154 TI - Synchronous position two-photon interference of random-phase grating. AB - By generalizing the phase structure of the random-phase grating we recently designed [Opt. Express21, 14056 (2013)OPEXFF1094-408710.1364/OE.21.014056], we show that non-HBT type (synchronous position) two-photon grating interference can be obtained, which physically relies on groups of multiple indistinguishable two photon paths modulated by the spatial distributions of phase modes. By properly selecting the random-phase structures, synchronous position subwavelength interference can be obtained, the period of which, in the two-photon interference domain, is decreased by a factor N (=3,4,5,6,...), depending on the slit number and random-phase structure, and the visibility of N-fold subwavelength interference fringes could be improved by increasing the slit number of the grating. The results show that modulation on two-photon paths via spatial arrangements of the phase modes offers the possibility to actively control the optical high-order coherence in the same optical scheme. PMID- 26367155 TI - Optimization of LED light spectrum to enhance colorfulness of illuminated objects with white light constraints. AB - Enhancing the colorfulness of illuminated objects is a promising application of LED lighting for commercial, exhibiting, and scientific purposes. This paper proposes a method to enhance the color of illuminated objects for a given polychromatic lamp. Meanwhile, the light color is restricted to white. We further relax the white light constraints by introducing soft margins. Based on the spectral and electrical characteristics of LEDs and object surface properties, we determine the optimal mixing of the LED light spectrum by solving a numerical optimization problem, which is a quadratic fractional programming problem by formulation. Simulation studies show that the trade-off between the white light constraint and the level of the color enhancement can be adjusted by tuning an upper limit value of the soft margin. Furthermore, visual evaluation experiments are performed to evaluate human perception of the color enhancement. The experiments have verified the effectiveness of the proposed method. PMID- 26367156 TI - TD-UAPO diffracted field evaluation for penetrable wedges with acute apex angle. AB - This study deals with the time domain (TD) diffraction phenomenon related to a penetrable acute-angled dielectric wedge. The transient diffracted field originated by an arbitrary function plane wave is evaluated via a convolution integral involving the TD diffraction coefficients, which are determined here in closed form, starting from the knowledge of the frequency domain counterparts. In particular, the inverse Laplace transform is applied to the uniform Asymptotic physical optics diffraction coefficients valid for the internal region of the wedge and the surrounding space. Diffraction by penetrable wedges in the TD framework is a challenging problem from the analytical point of view, and no other expressions are available in closed form for the diffraction coefficients associated with the considered problem. PMID- 26367157 TI - Strehl ratio: a tool for optimizing optical nulls and singularities. AB - In this paper a set of radial and azimuthal phase functions are reviewed that have a null Strehl ratio, which is equivalent to generating a central extinction in the image plane of an optical system. The study is conducted in the framework of Fraunhofer scalar diffraction, and is oriented toward practical cases where optical nulls or singularities are produced by deformable mirrors or phase plates. The identified solutions reveal unexpected links with the zeros of type-J Bessel functions of integer order. They include linear azimuthal phase ramps giving birth to an optical vortex, azimuthally modulated phase functions, and circular phase gratings (CPGs). It is found in particular that the CPG radiometric efficiency could be significantly improved by the null Strehl ratio condition. Simple design rules for rescaling and combining the different phase functions are also defined. Finally, the described analytical solutions could also serve as starting points for an automated searching software tool. PMID- 26367158 TI - Shannon information and ROC analysis in imaging. AB - Shannon information (SI) and the ideal-observer receiver operating characteristic (ROC) curve are two different methods for analyzing the performance of an imaging system for a binary classification task, such as the detection of a variable signal embedded within a random background. In this work we describe a new ROC curve, the Shannon information receiver operator curve (SIROC), that is derived from the SI expression for a binary classification task. We then show that the ideal-observer ROC curve and the SIROC have many properties in common, and are equivalent descriptions of the optimal performance of an observer on the task. This equivalence is described mathematically by an integral transform that maps the ideal-observer ROC curve onto the SIROC. This then leads to an integral transform relating the minimum probability of error, as a function of the odds against a signal, to the conditional entropy, as a function of the same variable. This last relation then gives us the complete mathematical equivalence between ideal-observer ROC analysis and SI analysis of the classification task for a given imaging system. We also find that there is a close relationship between the area under the ideal-observer ROC curve, which is often used as a figure of merit for imaging systems and the area under the SIROC. Finally, we show that the relationships between the two curves result in new inequalities relating SI to ROC quantities for the ideal observer. PMID- 26367159 TI - Structured decomposition design of partial Mueller matrix polarimeters. AB - Partial Mueller matrix polarimeters (pMMPs) are active sensing instruments that probe a scattering process with a set of polarization states and analyze the scattered light with a second set of polarization states. Unlike conventional Mueller matrix polarimeters, pMMPs do not attempt to reconstruct the entire Mueller matrix. With proper choice of generator and analyzer states, a subset of the Mueller matrix space can be reconstructed with fewer measurements than that of the full Mueller matrix polarimeter. In this paper we consider the structure of the Mueller matrix and our ability to probe it using a reduced number of measurements. We develop analysis tools that allow us to relate the particular choice of generator and analyzer polarization states to the portion of Mueller matrix space that the instrument measures, as well as develop an optimization method that is based on balancing the signal-to-noise ratio of the resulting instrument with the ability of that instrument to accurately measure a particular set of desired polarization components with as few measurements as possible. In the process, we identify 10 classes of pMMP systems, for which the space coverage is immediately known. We demonstrate the theory with a numerical example that designs partial polarimeters for the task of monitoring the damage state of a material as presented earlier by Hoover and Tyo [Appl. Opt.46, 8364 (2007)10.1364/AO.46.008364APOPAI1559-128X]. We show that we can reduce the polarimeter to making eight measurements while still covering the Mueller matrix subspace spanned by the objects. PMID- 26367160 TI - Light trajectory in Bessel-Gauss vortex beams. AB - We investigate the early stage of propagation of Bessel-Gauss vortex beams where a transition regime shows a progressive lateral expansion of the main intensity ring before reaching a diffraction-free regime. The eikonal equation is used to characterize the beam structure. The beam is featured by a family of hyperboloids with variable waists, generating a tapered tubular caustic. Our analytical results are in excellent agreement with numerical and experimental results. We show the transition regime can be well eliminated by using hollow input beams. PMID- 26367161 TI - Phase retrieval for multiple objects from their averaged diffraction. AB - The problem of reconstructing multiple objects from the average of their diffracted intensities is investigated. Reconstruction feasibility (uniqueness) depends on the number of objects, their support shapes and dimensionality, and an appropriately calculated constraint ratio. For objects with sufficiently different supports, and a favorable constraint ratio, the reconstruction problem has a unique solution. For objects with identical supports, there can be multiple solutions, even with a favorable constraint ratio. However, positivity of the objects and noncentrosymmetry of the support reduce the number of multiple solutions, and a unique solution may exist with a favorable constraint ratio. An iterative projection based algorithm to reconstruct the individual objects is described. The efficacy of the reconstruction algorithm and the uniqueness results are demonstrated by simulation. PMID- 26367162 TI - Light propagation in a two-dimensional medium with large inhomogeneities. AB - Propagation of a broad beam of light in a two-dimensional absorbing medium with large (compared to the light wavelength) inhomogeneities is considered. Within the small-angle approximation, an exact analytical solution to the radiative transfer equation is found for a phase function that decreases exponentially with the single-scattering angle. Attenuation of the total flux and evolution of the angular distribution of light are analyzed in detail. An accuracy of the small angle diffusion approximation is estimated. PMID- 26367163 TI - Three-dimensional simulation method of fish-eye lens distortion for a vehicle backup rear-view camera. AB - Recently, various cameras have been embedded in vehicles for driver safety and convenience. In this context, a backup rear-view camera has attracted increasing attention in helping drivers' parking convenience. Preinstallation of a rear-view camera requires the calibration of a wide-angle lens, such as a fish-eye lens, and the registration of guidelines to the three-dimensional (3D) scene. The proposed method provides a novel simulation method for the optical distortion of a wide-angle lens in a vehicle rear-view camera. The proposed method consists of three steps: (i) generation of the 3D virtual space, (ii) field number-based viewing angle estimation, and (iii) distorted image generation in the 3D space. The major contribution of this work is the lens specification-based simulation of 3D distortion for accurate and efficient preinstallation of vehicle rear-view cameras. The proposed simulation method can also be used to design a general optical imaging system for intelligent surveillance and medical imaging. PMID- 26367164 TI - Analytical expressions for characteristics of light scattering by arbitrarily shaped particles in the WKB approximation. AB - Light scattering in the Wentzel-Kramers-Brillouin (WKB) approximation is considered from the point of view of stereology. The extinction and absorption cross sections for an ensemble of chaotically oriented particles of arbitrary shape are expressed analytically through the chord length distribution. The analytical approximation for the scattering phase function is proposed. The derived analytical expressions are compared to the calculations with the discrete dipole-approximation method. PMID- 26367165 TI - Eigenvalue decomposition and least squares algorithm for depth resolution of wavenumber-scanning interferometry. AB - Depth resolution of depth-resolved interferometry evaluated by Fourier transform is limited by the range of phase shifting. A novel algorithm, the eigenvalue decomposition and least squares algorithm (EDLSA), is proposed. Experimental results obtained using depth-resolved wavenumber-scanning interferometry demonstrate that the EDLSA performs better than the Fourier transform and complex number least squares algorithm. Not requiring any a priori information, the algorithm can replace the Fourier transform in depth-resolved interferometry with improved depth resolution. PMID- 26367166 TI - Extended Huygens-Fresnel principle and optical waves propagation in turbulence: discussion. AB - Extended Huygens-Fresnel principle (EHF) currently is the most common technique used in theoretical studies of the optical propagation in turbulence. A recent review paper [J. Opt. Soc. Am. A31, 2038 (2014)JOAOD60740 323210.1364/JOSAA.31.002038] cites several dozens of papers that are exclusively based on the EHF principle. We revisit the foundations of the EHF, and show that it is burdened by very restrictive assumptions that make it valid only under weak scintillation conditions. We compare the EHF to the less-restrictive Markov approximation and show that both theories deliver identical results for the second moment of the field, rendering the EHF essentially worthless. For the fourth moment of the field, the EHF principle is accurate under weak scintillation conditions, but is known to provide erroneous results for strong scintillation conditions. In addition, since the EHF does not obey the energy conservation principle, its results cannot be accurate for scintillations of partially coherent beam waves. PMID- 26367167 TI - Virtual source simultaneous dual-surface method for uniform illumination. AB - We present a new simultaneous dual-surface design method for uniform illumination by introducing a virtual light source. This method is a combination of the equal optical path length condition and the tailored method. It can be applied to an extended light source after some optimization processes with a negative feedback algorithm. A solid lens to yield a circular uniform irradiance distribution is designed by using our method. Both optical simulation and experiment have been carried out to show that the experimental irradiance map is close to both the simulation result and the desired distribution, and the uniformity is higher than 0.9 while the light source is a 5050 LED chip with SMD package. The rays from the outside lens surface are of good topological invariance, which can give the potential to design more than two smooth freeform optical surfaces simultaneously by introducing multiple virtual point sources. PMID- 26367168 TI - Enhanced backscatter of optical beams reflected in turbulent air. AB - Optical beams propagating through air acquire phase distortions from turbulent fluctuations in the refractive index. While these distortions are usually deleterious to propagation, beams reflected in a turbulent medium can undergo a local recovery of spatial coherence and intensity enhancement referred to as enhanced backscatter (EBS). Here we validate the commonly used phase screen simulation with experimental results obtained from lab-scale experiments. We also verify theoretical predictions of the dependence of the turbulence strength on EBS. Finally, we present a novel algorithm called the "tilt-shift method" which allows detection of EBS in frozen turbulence, reducing the time required to detect the EBS signal. PMID- 26367169 TI - Vectorial spherical-harmonics representation of an inhomogeneous elliptically polarized plane wave. AB - In this paper, a generalization of the vectorial spherical-harmonics expansion of an inhomogeneous elliptically polarized plane wave is presented. The solution has been achieved using the Legendre functions generalized via hypergeometric and gamma functions, shifting the difficulty to the determination of only expansion coefficients. In order to validate the presented method, a Matlab code has been implemented. To compare the results a Mie scattering by a sphere is considered, then a truncation criterion for the numerical evaluation of the series is proposed, and the Mie scattering coefficients by perfectly conducting and dielectric spheres excited by an inhomogeneous elliptically polarized plane wave are shown. PMID- 26367170 TI - Scattering of light by gratings of metal-coated circular nanocylinders on a dielectric substrate. AB - Light scattering by a grating of the metal (Ag)-coated nanocylinders supported on the dielectric substrate is investigated using an accurate and rigorous formulation based on the recursive algorithm combined with the lattice sums technique. The proposed approach could be applied easily to the various configurations of the grating composed of the metal or metal-coated nanocylinders with different types and locations of the excitation sources. Special attention is paid to the three types of resonances: (a) surface plasmon resonances associated with the metal nanocylinders, (b) Rayleigh anomalies related with the periodic nature of the grating, and (c) resonances due to the coupling between the grating and the dielectric substrate. Near-field distribution of the magnetic field, which is parallel to the axis of the nanocylinders, is investigated numerically. Physical insight is given to the localization of the field along the interfaces of the metal nanocylinders, formation of the strong reflected field by the grating, and the field enhancement at the surface of the dielectric substrate. The accuracy of the numerical analyses has been tested based on the principle of the energy conservation. All these features are technologically important and have wide practical application from the viewpoint of the flexible design and fabrication of the plasmonic optical devices. PMID- 26367171 TI - Metrics and statistics of frequency of occurrence of metamerism in consumer cameras for natural scenes. AB - This paper presents metrics and statistics of frequency of occurrence of metamerism in three consumer cameras, viz., Canon 1D Mark III, Nikon D40, and Sony alpha7, using spectral and RGB images of natural scenes. Both sensor metamerism and observer metamerism of the cameras' sensors are studied. We use the concept of dissimilarity of two spectral power distributions in the spectral domain and the RGB domain for studying the occurrence sensor metamerism. Specifically, we use angular difference and digital equivalence approaches for this purpose. For studying the occurrence observer metamerism, we use the weighted Nimeroff's index for dissimilarity in the spectral domain with respect to the CIE color space along with the conventionally used CIE LAB color difference for dissimilarity in the CIE color space. The statistics of the frequency of occurrence of metamerism are generated on a dataset of 423 spectral images of indoor scenes in 5 illumination conditions and outdoor scenes in natural illumination conditions. Experiments show that about 18%-22% of the pixels in the images are metameric in the sense of angular difference. It is also observed that 1%-4% of the colors that would have appeared similar to human eyes are reproduced as distinct colors in the cameras. Dataset and details can be found at https://sites.google.com/site/dilipprasad/source-codes. PMID- 26367172 TI - Diversity Waves in Collapse-Driven Population Dynamics. AB - Populations of species in ecosystems are often constrained by availability of resources within their environment. In effect this means that a growth of one population, needs to be balanced by comparable reduction in populations of others. In neutral models of biodiversity all populations are assumed to change incrementally due to stochastic births and deaths of individuals. Here we propose and model another redistribution mechanism driven by abrupt and severe reduction in size of the population of a single species freeing up resources for the remaining ones. This mechanism may be relevant e.g. for communities of bacteria, with strain-specific collapses caused e.g. by invading bacteriophages, or for other ecosystems where infectious diseases play an important role. The emergent dynamics of our system is characterized by cyclic ''diversity waves'' triggered by collapses of globally dominating populations. The population diversity peaks at the beginning of each wave and exponentially decreases afterwards. Species abundances have bimodal time-aggregated distribution with the lower peak formed by populations of recently collapsed or newly introduced species while the upper peak--species that has not yet collapsed in the current wave. In most waves both upper and lower peaks are composed of several smaller peaks. This self-organized hierarchical peak structure has a long-term memory transmitted across several waves. It gives rise to a scale-free tail of the time-aggregated population distribution with a universal exponent of 1.7. We show that diversity wave dynamics is robust with respect to variations in the rules of our model such as diffusion between multiple environments, species-specific growth and extinction rates, and bet-hedging strategies. PMID- 26367173 TI - Novel Synthesis and Pharmacological Characterization of NOP Receptor Agonist 8 [(1S,3aS)-2,3,3a,4,5,6-Hexahydro-1H-phenalen-1-yl]-1-phenyl-1,3,8 triazaspiro[4.5]decan-4-one (Ro 64-6198). AB - The nociceptin/orphanin FQ opioid peptide (NOP) receptor is a widely expressed GPCR involved in the modulation of pain, anxiety, and motor behaviors. Dissecting the functional properties of this receptor is limited by the lack of systemically active ligands that are brain permeant. The small molecule NOP receptor selective, full agonist 8-[(1S,3aS)-2,3,3a,4,5,6-hexahydro-1H-phenalen-1-yl]-1 phenyl-1,3,8-triazaspiro[4.5]decan-4-one (Ro 64-6198) hydrochloride is an active, brain penetrant ligand, but its difficult and cost-prohibitive synthesis limits its widespread use and availability for animal studies. Here, we detail a more efficient and convenient method of synthesis, and use both in vitro and in vivo pharmacological assays to fully characterize this ligand. Specifically, we characterize the pharmacodynamics of Ro 64-6198 in cAMP and G-protein coupling in vitro and examine, for the first time, the effects of nociceptin/orphanin FQ and Ro 64-6198 in arrestin recruitment assays. Further, we examine the effects of Ro 64-6198 on analgesia, anxiety, and locomotor responses in vivo. This new synthesis and pharmacological characterization provide additional insights into the useful, systemically active, NOP receptor agonist Ro 64-6198. PMID- 26367174 TI - Crystal structure and characterization of a novel L-serine ammonia-lyase from Rhizomucor miehei. AB - L-serine ammonia-lyase, as a member of the beta-family of pyridoxal-5'-phosphate (PLP) dependent enzymes, catalyzes the conversion of L-serine (L-threonine) to pyruvate (alpha-ketobutyrate) and ammonia. The crystal structure of L-serine ammonia-lyase from Rhizomucor miehei (RmSDH) was solved at 1.76 A resolution by X ray diffraction method. The overall structure of RmSDH had the characteristic beta-family PLP dependent enzyme fold. It consisted of two distinct domains, both of which show the typical open twisted alpha/beta structure. A PLP cofactor was located in the crevice between the two domains, which was attached to Lys52 by a Schiff-base linkage. Unique residue substitutions (Gly78, Pro79, Ser146, Ser147 and Thr312) were discovered at the catalytic site of RmSDH by comparison of structures of RmSDH and other reported eukaryotic L-serine ammonia-lyases. Optimal pH and temperature of the purified RmSDH were 7.5 and 40 degrees C, respectively. It was stable in the pH range of 7.0-9.0 and at temperatures below 40 degrees C. This is the first crystal structure of a fungal L-serine ammonia lyase. It will be useful to study the catalytic mechanism of beta-elimination enzymes and will provide a basis for further enzyme engineering. PMID- 26367175 TI - Orai1 forms a signal complex with SK3 channel in gallbladder smooth muscle. AB - Orai1 is one of the key components of store-operated Ca(2+) entry (SOCE) involved in diverse physiological functions. Orai1 may associate with other proteins to form a signaling complex. In the present study, we investigated the interaction between Orai1 and small conductance Ca(2+)-activated potassium channel 3 (SK3). With the use of RNA interference technique, we found that the SOCE and its associated membrane hyperpolarization were reduced while Orai1 was knocked down by a specific Orai1 siRNA in guinea pig gallbladder smooth muscle. However, with the use of isometric tension measurements, our results revealed that agonist induced muscle contractility was significantly enhanced after Orai1 protein was knocked down or the tissue was treated by SK3 inhibitor apamin, but not affected by larger conductance Ca(2+)-activated potassium channel inhibitor iberiotoxin or intermediate conductance Ca(2+)-activated potassium channel inhibitor TRAM-34. In addition, in the presence of apamin, Orai1 siRNA had no additional effect on agonist-induced contraction. In coimmunoprecipitation experiment, SK3 and Orai1 pulled down each other. These data suggest that, Orai1 physically associated with SK3 to form a signaling complex in gallbladder smooth muscle. Ca(2+) entry via Orai1 activates SK3, resulting in membrane hyperpolarization in gallbladder smooth muscle. This hyperpolarizing effect of Orai1-SK3 coupling could serve to prevent excessive contraction of gallbladder smooth muscle in response to contractile agonists. PMID- 26367176 TI - Synthesis and characterization of the amyloid beta40 dimer model with a linker at position 30 adjacent to the intermolecular beta-sheet region. AB - Amyloid fibrils in senile plaque mainly consist of the 40-mer and 42-mer amyloid beta-proteins (Abeta40 and Abeta42). Although Abeta42 plays more important role in the pathogenesis of Alzheimer's disease (AD), Abeta40 could be involved in the progression of AD pathology because of its large amount. Recent studies revealed that variable sizes of Abeta oligomers contributed to the neuronal death and cognitive dysfunction. However, how large oligomeric species are responsible for AD pathogenesis remains unclear. We previously proposed a toxic dimer model of Abeta with turn structure at positions 22 and 23 using solid-state NMR and systematic proline replacement. Based on this model, we herein show the synthesis and biological activities of an E22P-Abeta40 dimer at position 30, which was connected to l,l-2,6-diaminopimeric acid. The E22P-Abeta40 dimer formed stable 6~8-mer oligomers without amyloid fibrils, but was not neurotoxic on human neuroblastoma cells. On the other hand, E22P-Abeta40 generated high molecular weight oligomers into fibrils, and showed the neurotoxicity. These results suggest that such kind of Abeta40 dimer with a parallel beta-sheet might not be pathological. PMID- 26367177 TI - miR-98 protects endothelial cells against hypoxia/reoxygenation induced-apoptosis by targeting caspase-3. AB - Endothelial dysfunction is one of the main pathophysiological processes involved in renal ischemia reperfusion injury. Our previous microarray study demonstrated that miR-98 was upregulated in the kidney with ischemia reperfusion injury (IRI). The present study was performed to investigate whether miR-98 was involved in the regulation of endothelial apoptosis under hypoxia and re-oxygenation (H/R) conditions. The dynamic changes of miR-98 in mouse IRI kidney and H/R HUVECs was measured. HUVECs were treated with HIF-1alpha siRNA to investigate the role of HIF-1alpha on miR-98 expression. The potential target genes of miR-98 were predicted by bioinformatics analyses. HUVECs were transfected with miR-98 mimics or inhibitor to confirm the role of miR-98 on the expression of target genes and hypoxia-induced apoptosis. The target gene was finally confirmed by dual luciferase reporter assay. Both of IRI and H/R induced significantly up regulation of miR-98 in the ischemic kidney and hypoxic HUVECs. HIF-1alpha siRNA remarkably down-regulated the expression of miR-98 in both normal and hypoxic HUVECs. The putative target genes of miR-98 included IL-6, IL-10 and caspase-3. MiR-98 mimics significantly inhibit caspase-3 expression in HUVECs, while anti miR-98 significantly up-regulated it. But no change of IL-6 and IL-10 levels was observed after miRNA transfection. miR-98 protected HUVECs against apoptosis induced by hypoxia, while anti-miR-98 had the reverse effect. Furthermore, the dual-luciferase reporter assay confirmed that miR-98 decreased the luciferase activity by targeting the 3' untranslated region of caspase-3. In conclusion, Renal IRI induces up-regulation of miR-98 dependent on HIF-1alpha, which protects endothelial cells against apoptosis by targeting caspase-3. PMID- 26367178 TI - A dominant negative form of inositol 1,4,5-trisphosphate receptor induces metacyclogenesis and increases mitochondrial density in Trypanosoma cruzi. AB - Inositol 1,4,5-trisphosphate receptor (IP3R) is a key regulator of intracellular Ca(2+) concentration that release Ca(2+) from Ca(2+) stores in response to various external stimuli. IP3R also works as a signal hub which form a platform for interacting with various proteins involved in diverse cell signaling. Previously, we have identified an IP3R homolog in the parasitic protist, Trypanosoma cruzi (TcIP3R). Parasites expressing reduced or increased levels of TcIP3R displayed defects in growth, transformation, and infectivity. In the present study, we established parasitic strains expressing a dominant negative form of TcIP3R, named DN-TcIP3R, to further investigate the physiological role(s) of TcIP3R. We found that the growth of epimastigotes expressing DN-TcIP3R was significantly slower than that of parasites with TcIP3R expression levels that were approximately 65% of wild-type levels. The expression of DN-TcIP3R in epimastigotes induced metacyclogenesis even in the normal growth medium. Furthermore, these epimastigotes showed the presence of dense mitochondria under a transmission electron microscope. Our findings confirm that TcIP3R is crucial for epimastigote growth, as previously reported. They also suggest that a strong inhibition of the IP3R-mediated signaling induces metacyclogenesis and that mitochondrial integrity is closely associated with this signaling. PMID- 26367180 TI - Genomic analyses and expression evaluation of thaumatin-like gene family in the cacao fungal pathogen Moniliophthora perniciosa. AB - Thaumatin-like proteins (TLPs) are found in diverse eukaryotes. Plant TLPs, known as Pathogenicity Related Protein (PR-5), are considered fungal inhibitors. However, genes encoding TLPs are frequently found in fungal genomes. In this work, we have identified that Moniliophthora perniciosa, a basidiomycete pathogen that causes the Witches' Broom Disease (WBD) of cacao, presents thirteen putative TLPs from which four are expressed during WBD progression. One of them is similar to small TLPs, which are present in phytopathogenic basidiomycete, such as wheat stem rust fungus Puccinia graminis. Fungi genomes annotation and phylogenetic data revealed a larger number of TLPs in basidiomycetes when comparing with ascomycetes, suggesting that these proteins could be involved in specific traits of mushroom-forming species. Based on the present data, we discuss the contribution of TLPs in the combat against fungal competitors and hypothesize a role of these proteins in M. perniciosa pathogenicity. PMID- 26367179 TI - Association of HADHA with human RNA silencing machinery. AB - In RNA silencing, small RNAs produced by dicer mediate target repression guided by RNA induced silencing complex (RISC). To effectively mediate this response, one or more proteins are employed at each stage. In the present study, we investigated HADHA, a new component in the human RNA silencing machinery. Immunoprecipitation analysis revealed that, HADHA associates with dicer complex and immunohistochemical studies confirmed its co localization with Dicer in the cytoplasm. Further, over expression of HADHA resulted in higher abundance levels of mature miRNA against a reduction in respective precursor levels and vice versa in HADHA knocked down cells. These findings suggest an auxiliary role for HADHA in miRNA biogenesis and help in better understanding of molecular mechanisms underlying RNAi pathway in mammals. PMID- 26367182 TI - Automatic Combination of Operators in a Genetic Algorithm to Solve the Traveling Salesman Problem. AB - Genetic algorithms are powerful search methods inspired by Darwinian evolution. To date, they have been applied to the solution of many optimization problems because of the easy use of their properties and their robustness in finding good solutions to difficult problems. The good operation of genetic algorithms is due in part to its two main variation operators, namely, crossover and mutation operators. Typically, in the literature, we find the use of a single crossover and mutation operator. However, there are studies that have shown that using multi-operators produces synergy and that the operators are mutually complementary. Using multi-operators is not a simple task because which operators to use and how to combine them must be determined, which in itself is an optimization problem. In this paper, it is proposed that the task of exploring the different combinations of the crossover and mutation operators can be carried out by evolutionary computing. The crossover and mutation operators used are those typically used for solving the traveling salesman problem. The process of searching for good combinations was effective, yielding appropriate and synergic combinations of the crossover and mutation operators. The numerical results show that the use of the combination of operators obtained by evolutionary computing is better than the use of a single operator and the use of multi-operators combined in the standard way. The results were also better than those of the last operators reported in the literature. PMID- 26367181 TI - Differential Relevance of NF-kappaB and JNK in the Pathophysiology of Hemorrhage/Resususcitation-Induced Liver Injury after Chronic Ethanol Feeding. AB - BACKGROUND: Chronic ethanol (EtOH) abuse worsens pathophysiological derangements after hemorrhagic shock and resuscitation (H/R) that induce hepatic injury and strong inflammatory changes via JNK and NF-kappaB activation. Inhibiting JNK with a cell-penetrating, protease-resistant peptide D-JNKI-1 after H/R in mice with healthy livers ameliorated these effects. Here, we studied if JNK inhibition by D JNKI-1 in chronically EtOH-fed mice after hemorrhagic shock prior to the onset of resuscitation also confers protection. METHODS: Male mice were fed a Lieber DeCarli diet containing EtOH or an isocaloric control (ctrl) diet for 4 weeks. Animals were hemorrhaged for 90 min (32 +/- 2 mm Hg) and randomly received either D-JNKI-1 (11 mg/kg, intraperitoneally, i. p.) or sterile saline as vehicle (veh) immediately before the onset of resuscitation. Sham animals underwent surgical procedures without H/R and were either D-JNKI-1 or veh treated. Two hours after resuscitation, blood samples and liver tissue were harvested. RESULTS: H/R induced hepatic injury with increased systemic interleukin (IL)-6 levels, and enhanced local gene expression of NF-kappaB-controlled genes such as intercellular adhesion molecule (ICAM)-1 and matrix metallopeptidase (MMP)9. c Jun and NF-kappaB phosphorylation were increased after H/R. These effects were further increased in EtOH-fed mice after H/R. D-JNKI-1 application inhibited the proinflammatory changes and reduced significantly hepatic injury after H/R in ctrl-fed mice. Moreover, D-JNKI-1 reduces in ctrl-fed mice the H/R-induced c-Jun and NF-kappaB phosphorylation. However, in chronically EtOH-fed mice, JNK inhibition did not prevent the H/R-induced hepatic damage and proinflammatory changes nor c-Jun and NF-kappaB phosphorylation after H/R. CONCLUSIONS: These results indicate, that JNK inhibition is protective only in not pre-harmed liver after H/R. In contrast, the pronounced H/R-induced liver damage in mice being chronically fed with ethanol cannot be prevented by JNK inhibition after H/R and seems to be under the control of NF-kappaB. PMID- 26367183 TI - Fetus with Casamassima-Morton-Nance Syndrome and Limb-Body Wall Defect: Presentation of a Novel Association and Review of the Phenotype. AB - In 1981, Casamassima and colleagues described an autosomal recessive syndrome of spondylocostal dysostosis associated with anal and urogenital anomalies. Here, I describe 1 new fetus who presented with limb-body wall defect as a novel association, compile 7 patients, and review the clinical phenotype of Casamassima Morton-Nance syndrome. This appears to be the 1st Casamassima-Morton-Nance syndrome fetus with this complex malformation. In light of this manifestation, a detailed comparative phenotypic analysis of published patients revealed a heterogeneous syndrome with significant clinical variability. Accordingly, it is proposed that Casamassima-Morton-Nance syndrome should be considered in those patients with the combination of a short and asymmetric thorax with rib and vertebral anomalies and scoliosis (spondylocostal-like pattern), anal atresia, absent external genitalia, renal and urethral abnormalities (caudal dysgenesis complex), craniofacial dysmorphic features (mainly flat nose with anteverted nares, low-set/abnormal ears, and short neck), hydrops, oligohydramnios, and a poor clinical outcome. PMID- 26367184 TI - Parametric uncertainty and global sensitivity analysis in a model of the carotid bifurcation: Identification and ranking of most sensitive model parameters. AB - In computational cardiovascular models, parameters are one of major sources of uncertainty, which make the models unreliable and less predictive. In order to achieve predictive models that allow the investigation of the cardiovascular diseases, sensitivity analysis (SA) can be used to quantify and reduce the uncertainty in outputs (pressure and flow) caused by input (electrical and structural) model parameters. In the current study, three variance based global sensitivity analysis (GSA) methods; Sobol, FAST and a sparse grid stochastic collocation technique based on the Smolyak algorithm were applied on a lumped parameter model of carotid bifurcation. Sensitivity analysis was carried out to identify and rank most sensitive parameters as well as to fix less sensitive parameters at their nominal values (factor fixing). In this context, network location and temporal dependent sensitivities were also discussed to identify optimal measurement locations in carotid bifurcation and optimal temporal regions for each parameter in the pressure and flow waves, respectively. Results show that, for both pressure and flow, flow resistance (R), diameter (d) and length of the vessel (l) are sensitive within right common carotid (RCC), right internal carotid (RIC) and right external carotid (REC) arteries, while compliance of the vessels (C) and blood inertia (L) are sensitive only at RCC. Moreover, Young's modulus (E) and wall thickness (h) exhibit less sensitivities on pressure and flow at all locations of carotid bifurcation. Results of network location and temporal variabilities revealed that most of sensitivity was found in common time regions i.e. early systole, peak systole and end systole. PMID- 26367185 TI - Role of word-of-mouth for programs of voluntary vaccination: A game-theoretic approach. AB - We propose a model describing the synergetic feedback between word-of-mouth (WoM) and epidemic dynamics controlled by voluntary vaccination. The key feature consists in combining a game-theoretic model for the spread of WoM and a compartmental model describing VSIR disease dynamics in the presence of a program of voluntary vaccination. We evaluate and compare two scenarios for determinants of behavior, depending on what WoM disseminates: (1) vaccine advertising, which may occur whether or not an epidemic is ongoing and (2) epidemic status, notably disease prevalence. Understanding the synergy between the two strategies could be particularly important for designing voluntary vaccination campaigns. We find that, in the initial phase of an epidemic, vaccination uptake is determined more by vaccine advertising than the epidemic status. As the epidemic progresses, epidemic status becomes increasingly important for vaccination uptake, considerably accelerating vaccination uptake toward a stable vaccination coverage. PMID- 26367187 TI - A Clinical Trial to Introduce Voluntary Medical Male Circumcision for HIV Prevention in Areas of High Prevalence in the Dominican Republic. AB - BACKGROUND: Voluntary Medical Male Circumcision (VMMC) is an effective strategy to reduce the risk of HIV infection. Studies conducted in the Dominican Republic (DR) suggest that acceptability of VMMC among men may be as high as 67%. The goal of this clinical trial was to assess the acceptability, uptake and safety for VMMC services in two areas of high HIV prevalence in the country. METHODS: This was a single-arm, non-randomized, pragmatic clinical trial. Study personnel received background information about the risks and benefits of VMMC and practical training on the surgical technique. A native speaking research assistant administered a questionnaire of demographics, sexual practices and knowledge about VMMC. One week after the surgery, participants returned for wound inspection and to answer questions about their post-surgical experience. RESULTS: 539 men consented for the study. Fifty seven were excluded from participation for medical or anatomical reasons and 28 decided not to have the procedure after providing consent. A total of 454 men were circumcised using the Forceps Guided Method Under Local Anesthesia. The rate of adverse events (AE) was 4.4% (20% moderate, 80% mild). There were no serious AEs and all complications resolved promptly with treatment. Eighty eight percent of clients reported being "very satisfied" and 12% were "somewhat satisfied" with the outcome at the one-week postoperative visit. CONCLUSIONS: Recruitment and uptake were satisfactory. Client satisfaction with VMMC was high and the rate of AEs was low. Roll out of VMMC in targeted areas of the DR is feasible and should be considered. TRIAL REGISTRATION: ClinicalTrials.gov NCT02337179. PMID- 26367188 TI - Suspected poisoning of domestic animals by pesticides. AB - A retrospective study was carried out by reviewing all suspected cases of domestic animal poisoning attributed to pesticides, reported to the Milan Poison Control Centre (MPCC) between January 2011 and December 2013. During this period, pesticides were found to be responsible for 37.3% of all suspected poisoning enquiries received (815). The most commonly species involved was the dog (71.1% of calls) followed by the cat (15.8%), while a limited number of cases involved horses, goats and sheep. Most cases of exposure (47.1%) resulted in mild to moderate clinical signs. The outcome was reported in 59.9% of these cases, with death occurring in 10.4% of them. Insecticides (40.8%) proved to be the most common group of pesticides involved and exposure to pyrethrins-pyrethroids accounted for the majority of calls. According to the MPCC data, there has been a decrease in the number of suspected poisonings cases attributed to pesticides that have been banned by the EU, including aldicarb, carbofuran, endosulfan and paraquat. In contrast, there has been an increase of suspected poisoning cases attributed to the neonicotinoids, imidacloprid and acetamiprid, probably due to their widespread use in recent years. Cases of suspected poisoning that involved exposure to rodenticides accounted for 27.6% of calls received by the MPCC and anticoagulant rodenticides were the primary cause of calls, with many cases involving brodifacoum and bromadiolone. Herbicides were involved in 14.2% of calls related to pesticides and glyphosate was the main culprit in cases involving dogs, cats, horses, goats and sheep. As far as exposure to molluscicides (11.5%) and fungicides (5.9%), most of the cases involved dogs and the suspected poisoning agents were metaldehyde and copper compounds respectively. The data collected are useful in determining trends in poisoning episodes and identifying newly emerging toxicants, thus demonstrating the prevalence of pesticides as causative agents in animal poisonings. PMID- 26367186 TI - Diagnostic Yield and Complications of Bronchoscopy for Peripheral Lung Lesions. Results of the AQuIRE Registry. AB - RATIONALE: Advanced bronchoscopy techniques such as electromagnetic navigation (EMN) have been studied in clinical trials, but there are no randomized studies comparing EMN with standard bronchoscopy. OBJECTIVES: To measure and identify the determinants of diagnostic yield for bronchoscopy in patients with peripheral lung lesions. Secondary outcomes included diagnostic yield of different sampling techniques, complications, and practice pattern variations. METHODS: We used the AQuIRE (ACCP Quality Improvement Registry, Evaluation, and Education) registry to conduct a multicenter study of consecutive patients who underwent transbronchial biopsy (TBBx) for evaluation of peripheral lesions. MEASUREMENTS AND MAIN RESULTS: Fifteen centers with 22 physicians enrolled 581 patients. Of the 581 patients, 312 (53.7%) had a diagnostic bronchoscopy. Unadjusted for other factors, the diagnostic yield was 63.7% when no radial endobronchial ultrasound (r-EBUS) and no EMN were used, 57.0% with r-EBUS alone, 38.5% with EMN alone, and 47.1% with EMN combined with r-EBUS. In multivariate analysis, peripheral transbronchial needle aspiration (TBNA), larger lesion size, nonupper lobe location, and tobacco use were associated with increased diagnostic yield, whereas EMN was associated with lower diagnostic yield. Peripheral TBNA was used in 16.4% of cases. TBNA was diagnostic, whereas TBBx was nondiagnostic in 9.5% of cases in which both were performed. Complications occurred in 13 (2.2%) patients, and pneumothorax occurred in 10 (1.7%) patients. There were significant differences between centers and physicians in terms of case selection, sampling methods, and anesthesia. Medical center diagnostic yields ranged from 33 to 73% (P = 0.16). CONCLUSIONS: Peripheral TBNA improved diagnostic yield for peripheral lesions but was underused. The diagnostic yields of EMN and r-EBUS were lower than expected, even after adjustment. PMID- 26367189 TI - Organohalogenated contaminants in white-tailed eagle (Haliaeetus albicilla) nestlings: An assessment of relationships to immunoglobulin levels, telomeres and oxidative stress. AB - Biomagnifying organohalogenated compounds (OHCs) may have adverse effects on the health of birds, especially marine avian top predators that accumulate high OHC loads. Contaminants may impair the humoral immunity and also influence the antioxidant enzyme activity (i.e. oxidative stress). Moreover, physical conditions and oxidative stress during development may reduce telomere lengths, one of the main mechanisms explaining cell senescence. To examine the potential effects of environmental contaminants on physiological biomarkers of health, OHCs with different 'physicochemical' properties were related to immunoglobulin Y levels (IgY; humoral immunity), superoxide dismutase enzyme (SOD) activity in blood plasma, and telomere length (measured in red blood cells) in individual 7 8weeks old nestlings (n=35) of white-tailed eagles (Haliaeetus albicilla) in the Norwegian Sub-Arctic. Different organochlorines (OCs) and perfluoroalkylated substances (PFASs) were measured in blood plasma of nestlings, demonstrating higher concentrations of the emerging contaminants (PFASs), notably perfluorooctane sulfonate (PFOS), compared to legacy OCs. There were no relationships between the contaminant loads and plasma IgY levels. Moreover, differences between years were found for telomere lengths, but this was not related to contaminants and more likely a result of different developmental conditions. However, there were significant and negative relationships between the OC loadings and the SOD activity. This suggests that some legacy OCs challenge the antioxidant capacity in nestlings of white-tailed eagles. PMID- 26367190 TI - Levels and profiles of brominated and chlorinated contaminants in human breast milk from Thessaloniki, Greece. AB - Human breast milk samples (n=87) collected between July 2004 and July 2005 from primipara and multipara mothers from Thessaloniki, Greece were analysed for six groups of persistent organic pollutants (POPs): polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethane and its metabolites (DDTs), chlordane compounds (CHLs), hexachlorocyclohexane isomers (HCHs) and hexachlorobenzene (HCB). DDTs [median: 410ng/g lipid weight (lw)], PCBs (median: 90ng/g lw) and HCHs (median: 40ng/g lw) were the predominantly identified compounds in all the breast milk samples. Levels of PBDEs (median: 1.5ng/g lw) in human breast milk samples from Thessaloniki, Greece were lower compared to other countries. Maternal age had a positive correlation with most compounds, but not with PBDEs. Women with a higher occupational exposure to PBDEs (i.e., working in office environments) had higher PBDE concentrations than all others and showed strong correlations, especially for BDE 47 and BDE 153. None of the analysed compounds showed any correlation with parity. Based on these levels, the daily intake of each group of POPs via human milk was calculated and compared with the tolerable daily intakes (TDI) or the reference doses (RfD). For the majority of samples (85 out of 87) a higher daily intake of PCBs than the TDI was calculated, while 11 out of 87 samples had a higher HCB intake than the TDI. The TDI and the RfD were not exceeded for DDTs and PBDEs, respectively. This is the first report of brominated flame retardants in human breast milk from Greece. PMID- 26367191 TI - Materno-foetal leptin and insulin-like growth factor in low birth weight neonates. AB - Low birth weight (LBW) is a health concern in developing countries. Leptin and insulin-like growth factor-I (IGF-I) are factors that influence LBW. A case control study was conducted at Medani hospital, Sudan. Cases were women who had LBW deliveries ( 2,500 g) and controls were women with normal-weight babies ( 2.500 - 4,000 g). Sociodemographic and obstetrical characteristics were gathered from both groups and leptin and IGF-I levels were measured by ELISA. Cases and controls (45 in each arm) were matched in their basic data. The median (interquartile) of maternal leptin levels [9.9 (1.9 - 21.8) vs. 16.0 (9.6 - 20.8), ng/ml; P0.001] and IGF-I [1.6 (0.7 - 20.0) vs. 6.1 (4.3 - 7.1) ng/ml ; P 0.001] were significantly lower in cases than in controls. Likewise, cord serum leptin [5.8 (2.1 - 12.6) vs. 20.0 (5.1 - 37.8) ng/ml; P0.001] and cord serum IGF I [1.7 (1.3 - 2.0) vs. 6.9 (5.9 - 7.4) ng/ml; P0.001] levels were significantly lower in cases than in controls. Significant positive correlation was found between birth weight and cord leptin ( r0.398), maternal ( r0.795) and cord ( r0.863) IGF-I levels. Maternal and cord leptin and IGF-I levels were significantly lower in LBW babies. PMID- 26367192 TI - Bioorthogonal Catalysis: A General Method To Evaluate Metal-Catalyzed Reactions in Real Time in Living Systems Using a Cellular Luciferase Reporter System. AB - The development of abiological catalysts that can function in biological systems is an emerging subject of importance with significant ramifications in synthetic chemistry and the life sciences. Herein we report a biocompatible ruthenium complex [Cp(MQA)Ru(C3H5)](+)PF6(-) 2 (Cp = cyclopentadienyl, MQA = 4 methoxyquinoline-2-carboxylate) and a general analytical method for evaluating its performance in real time based on a luciferase reporter system amenable to high throughput screening in cells and by extension to evaluation in luciferase transgenic animals. Precatalyst 2 activates alloc-protected aminoluciferin 4b, a bioluminescence pro-probe, and releases the active luminophore, aminoluciferin (4a), in the presence of luciferase-transfected cells. The formation and enzymatic turnover of 4a, an overall process selected because it emulates pro drug activation and drug turnover by an intracellular target, is evaluated in real time by photon counting as 4a is converted by intracellular luciferase to oxyaminoluciferin and light. Interestingly, while the catalytic conversion (activation) of 4b to 4a in water produces multiple products, the presence of biological nucleophiles such as thiols prevents byproduct formation and provides almost exclusively luminophore 4a. Our studies show that precatalyst 2 activates 4b extracellularly, exhibits low toxicity at concentrations relevant to catalysis, and is comparably effective in two different cell lines. This proof of concept study shows that precatalyst 2 is a promising lead for bioorthogonal catalytic activation of pro-probes and, by analogy, similarly activatable pro drugs. More generally, this study provides an analytical method to measure abiological catalytic activation of pro-probes and, by analogy with our earlier studies on pro-Taxol, similarly activatable pro-drugs in real time using a coupled biological catalyst that mediates a bioluminescent readout, providing tools for the study of imaging signal amplification and of targeted therapy. PMID- 26367193 TI - Targeting Persons With or At High Risk for Chronic Obstructive Pulmonary Disease by State-based Surveillance. AB - The Behavioral Risk Factor Surveillance System (BRFSS) survey is used to estimate chronic obstructive pulmonary disease (COPD) prevalence and could be expanded to describe respiratory symptoms in the general population and to characterize persons with or at high risk for the disease. Tobacco duration and respiratory symptom questions were added to the 2012 South Carolina BRFSS. Data concerning sociodemographics, chronic illnesses, health behaviors, and respiratory symptoms were collected in 9438 adults >= 35 years-old. Respondents were categorized as having COPD, high risk, or low risk for the disease. High risk was defined as no self-reported COPD, >= 10 years' tobacco use, and >= 1 respiratory symptom (frequent productive cough or shortness of breath (SOB), or breathing problems affecting activities). Prevalence of self-reported and high-risk COPD were 9.1% and 8.0%, respectively. Overall, 17.3%, 10.6%, and 5.2% of all respondents reported activities limited by breathing problems, frequent productive cough, and frequent SOB, respectively. The high-risk group was more likely than the COPD group to report a productive cough and breathing problems limiting activities as well as being current smokers, male, and African-American. Health impairment was more severe in the COPD than the high-risk group, and both were worse than the low-risk group. CONCLUSIONS: Persons at high risk for COPD share many, but not all, of the characteristics of persons diagnosed with the disease. Additional questions addressing smoking duration and respiratory symptoms in the BRFSS identifies groups at high risk for having or developing COPD who may benefit from smoking cessation and case-finding interventions. PMID- 26367194 TI - Electro-hyperthermia inhibits glioma tumorigenicity through the induction of E2F1 mediated apoptosis. AB - PURPOSE: Modulated electro-hyperthermia (mEHT), also known as oncothermia, shows remarkable treatment efficacies for various types of tumours, including glioma. The aim of the present study was to investigate the molecular mechanism underlying phenotypic changes in oncothermic cancer cells. MATERIALS AND METHODS: U87-MG and A172 human glioma cells were exposed to mEHT (42 degrees C/60 min) three times with a 2-day interval and subsequently tested for growth inhibition using MTS, FACS and microscopic analysis. To obtain insights into the molecular changes in response to mEHT, global changes in gene expression were examined using RNA sequencing. For in vivo evaluation of mEHT, we used U87-MG glioma xenografts grown in nude mice. RESULTS: mEHT inhibited glioma cell growth through the strong induction of apoptosis. The transcriptomic analysis of differential gene expression under mEHT showed that the anti-proliferative effects were induced through a subset of molecular alterations, including the up-regulation of E2F1 and CPSF2 and the down-regulation of ADAR and PSAT1. Subsequent Western blotting revealed that mEHT increased the levels of E2F1 and p53 and decreased the level of PARP-1, accelerating apoptotic signalling in glioma cells. mEHT significantly suppressed the growth of human glioma xenografts in nude mice. We also observed that mEHT dramatically reduced the portion of CD133(+) glioma stem cell population and suppressed cancer cell migration and sphere formation. CONCLUSIONS: These findings suggest that mEHT suppresses glioma cell proliferation and mobility through the induction of E2F1-mediated apoptosis and might be an effective treatment for eradicating brain tumours. PMID- 26367196 TI - Recombinant phosphoprotein based single serum dilution ELISA for rapid serological detection of Newcastle disease virus. AB - Newcastle disease virus (NDV) is the causative agent of a highly contagious disease in avian species. All strains of NDV belong to avian paramyxovirus serotype-1. The disease is endemic in different parts of the world and vaccination is the only way to protect birds from NDV infection. The virus non structural phosphoprotein (P) is the second most abundant protein and a major modulator of viral replication. Although P protein shows lesser evolutionary divergence among NDV isolates, it is known to be highly divergent among different avian paramyxovirus serotypes. In the present study, a recombinant P protein based single serum dilution ELISA was developed which showed better sensitivity, specificity and accuracy as compared to conventional methods for NDV detection. The recombinant P protein based ELISA could be an alternative to existing diagnostics against NDV infection in chickens. PMID- 26367197 TI - Influence of footwear designed to boost energy return on running economy in comparison to a conventional running shoe. AB - Running economy is a reflection of the amount of inspired oxygen required to maintain a given velocity and is considered a determining factor for running performance. Athletic footwear has been advocated as a mechanism by which running economy can be enhanced. New commercially available footwear has been developed in order to increase energy return, although their efficacy has not been investigated. This study aimed to examine the effects of energy return footwear on running economy in relation to conventional running shoes. Twelve male runners completed 6-min steady-state runs in conventional and energy return footwear. Overall, oxygen consumption (VO2), heart rate, respiratory exchange ratio, shoe comfort and rating of perceived exertion were assessed. Moreover, participants subjectively indicated which shoe condition they preferred for running. Differences in shoe comfort and physiological parameters were examined using Wilcoxon signed-rank tests, whilst shoe preferences were tested using a chi square analysis. The results showed that VO2 and respiratory exchange ratio were significantly lower, and shoe comfort was significantly greater, in the energy return footwear. Given the relationship between running economy and running performance, these observations indicate that the energy return footwear may be associated with enhanced running performance in comparison to conventional shoes. PMID- 26367195 TI - A comprehensive review of pacritinib in myelofibrosis. AB - The first-in-class JAK1/JAK2 inhibitor ruxolitinib inhibits JAK/STAT signaling, inducing durable reductions in splenomegaly and constitutional symptoms in patients with myelofibrosis. However, the association of ruxolitinib therapy with myelosuppression indicates the continued need for optimal treatment choices in myelofibrosis. Pacritinib, a dual JAK2 and FLT3 inhibitor, improves disease related symptoms and signs with manageable gastrointestinal toxicity in patients with myelofibrosis with splenomegaly and high-risk features, without causing overt myelosuppression, and therefore may provide an important treatment option for a range of patients with myelofibrosis. This article examines the role of JAK2 and FLT3 signaling in myelofibrosis and provides an overview of the clinical development of pacritinib as a new therapy for myelofibrosis. PMID- 26367198 TI - Swarming behaviour associated with group cohesion in tree-dwelling bats. AB - Group living of social species increases the individual survival rate and enhances optimal exploitation of resources within their environment. Groups of cryptic tree-dwelling bats perform frequent roost switching on relatively long distances, whereas groups are temporarily disintegrated during foraging that precedes moving into new roost. In this study, we attempted to elucidate a mechanism in which group members can select new roost from a large set of potential roosting sites without disintegration of the whole group. Exploring the activity at the front of the tree hollows, recorded by automatic infrared monitors, we found that the swarming activity of Leisler's bats was performed during the whole night and was concentrated before the civil twilight at occupied roosts. A generalized linear model revealed significant positive association between the group size and swarming activity while season had negative but smaller effect. As bats swarmed the whole night also at sites that were less occupied or even unoccupied, we suggest that members of a bat colony selected new roost from a potentially larger set of available roosting sites. Thus, we propose a possible signalling role of swarming as a threshold behaviour that ensures group cohesion during roost switching. PMID- 26367199 TI - A Girl With Beckwith-Wiedemann Syndrome and Pseudohypoparathyroidism Type 1B Due to Multiple Imprinting Defects. AB - CONTEXT: Several patients with Beckwith-Wiedemann Syndrome (BWS) with multiple imprinting defects found by genetic analysis have been described. However, only two cases have been described with both genetic and clinical signs and symptoms of multiple diseases caused by imprinting defects. CASE DESCRIPTION: The girl in this case presented at the age of 6 months with morbid obesity (body mass index, +7.5 SDS) and a large umbilical hernia. Genetic analysis showed BWS (hypomethylation of the KCNQ1OT1 gene). Calcium homeostasis was normal, and she had no signs of Albright hereditary osteodystrophy. At the age of 10 years, she presented with fatigue, and laboratory analyses showed marked hypocalcemia with signs of PTH resistance, but without evidence for Albright hereditary osteodystrophy, thus suggesting pseudohypoparathyroidism type 1B. Consistent with this diagnosis, methylation analysis of the GNAS complex revealed hypomethylation (about 20%) of the GNAS exon 1A, NESPAS, and GNASXL loci and hypermethylation (100% methylation) of the NESP locus. CONCLUSIONS: Imprinting defects at several different loci can occur in some patients, thus causing multiple different diseases. Symptoms of pseudohypoparathyroidism type 1B may be absent at diagnosis of BWS, yet prolonged subclinical hypocalcemia and/or hyperphosphatemia can have negative consequences (eg, intracerebral calcifications, myocardial dysfunction). We therefore suggest that patients with an imprinting disorder should be monitored for elevations in PTH, and epigenetic analysis of the GNAS complex locus should be considered. PMID- 26367201 TI - Biomechanical Changes During a 50-minute Run in Different Footwear and on Various Slopes. AB - The effects of footwear and inclination on running biomechanics over short intervals are well documented. Although recognized that exercise duration can impact running biomechanics, it remains unclear how biomechanics change over time when running in minimalist shoes and on slopes. Our aims were to describe these biomechanical changes during a 50-minute run and compare them to those observed in standard shoes. Thirteen trained recreational male runners ran 50 minutes at 65% of their maximal aerobic velocity on a treadmill, once in minimalist shoes and once in standard shoes, 1 week apart in a random order. The 50-minute trial was divided into 5-minute segments of running at 0%, +5%, and -5% of treadmill incline sequentially. Data were collected using photocells, high-speed video cameras, and plantar-pressure insoles. At 0% incline, runners exhibited reduced leg stiffness and plantar flexion angles at foot strike and lower plantar pressure at the forefoot and toes in minimalist shoes from minute 34 of the protocol onward. However, only reduced plantar pressure at the toes was observed in standard shoes. Overall, similar biomechanical changes with increased exercise time were observed on the uphill and downhill inclines. The results might be due to the unfamiliarity of subjects to running in minimalist shoes. PMID- 26367200 TI - Bone Mineral Density as a Predictor of Subsequent Wrist Fractures: Findings From the Women's Health Initiative Study. AB - CONTEXT: Wrist fractures are common among postmenopausal women. Associations of bone mineral density (BMD) and 10-year predicted risk of major osteoporotic fracture (MOF) with wrist fractures are poorly characterized. OBJECTIVE: The objective was to examine associations between the Fracture Risk Assessment Tool (FRAX)-predicted risk of MOF, BMD, BMD change, and wrist fracture. DESIGN: This was a prospective observational study with a mean follow-up of 8.5 years. SETTING: This study included 40 US centers. PARTICIPANTS: A total of 11 392 participants from the Women's Health Initiative BMD Cohort aged 50-79 years at baseline were included in this study. INTERVENTIONS: None. MAIN OUTCOME: The goal was to measure incident wrist fracture. RESULTS: A FRAX-predicted MOF risk >=9.3% identified 17% of the women aged <65 years who subsequently experienced wrist fracture. Each one standard deviation lower BMD was associated with higher wrist fracture risk, with adjusted hazard ratio (95% confidence interval) of 1.66 (1.42 1.93) for femoral neck (FN) BMD and 1.45 (1.28-1.64) for lumbar spine BMD. Compared with FN BMD T score >= -1.0, wrist fracture adjusted hazard ratios (95% confidence interval) were: 1.51 (1.06-2.16) for a T score between -1.01 and 1.49; 1.93 (1.36-2.72) for T score between -1.50 and -1.99; 2.52 (1.77-3.60) for a T score between -2.00 and -2.49; and 2.65 (1.78-3.95) for a T score <= -2.5. Decrease in FN BMD between baseline and year 3 was associated with increased risk of subsequent wrist fracture; however, change in lumbar spine BMD was not. CONCLUSIONS: Lumbar spine and femoral neck BMDs were associated with incident wrist fracture, but the FRAX threshold recommended to identify screening candidates did not identify the majority of women who subsequently experienced wrist fracture. Improved understanding of determinants of wrist fractures is warranted. PMID- 26367202 TI - The complete mitochondrial genome sequence of Mustela eversmannii (Carnivora: Mustelidae). AB - In this study, the complete mitochondrial genome of Steppe polecat, Mustela eversmannii, was sequenced for the first time using muscle tissue. The mitochondrial genome is a circular molecule of 16 463 bp in length and overall base composition is A (32.7%), T (27.3%), C (26.1%), and G (13.9%), which indicates a strong A-T bias. A phylogenetic analysis on the basis of 13 protein coding genes and two rRNA genes of 10 Mustela species' mitochondrial genomes using maximum likelihood (ML) and Bayesian inference (BI) demonstrated that these Mustela species were clustered into two clades and M. eversmannii was close to M. putorius. PMID- 26367204 TI - New Contact Allergens: 2008 to 2015. AB - Every year, new contact allergens, chemicals reported to have caused contact allergy/ACD for the first time, are described in literature. In the journals Contact Dermatitis and Dermatitis, 172 such compounds were identified in the period 2008-2015, 119 of which induced ACD. These are presented with the following data: name, synonyms, Chemical Abstracts Service (CAS) number, patch test data, function or class, causative product, number of patients, occupation (in case of occupational ACD), additional clinical data (if applicable), and references. Approximately one third of the new allergens were ingredients of cosmetics, followed by drugs causing occupational ACD (18%), chemicals in rubber, plastics, and paints (9%), drugs causing a drug eruption (9%), as well as chemicals used in laboratories inducing occupational ACD (8%). In 40%, the dermatitis was occupationally acquired. Fifty-three other chemicals causing contact allergy as indicated by positive patch test reactions only are shown without specifics. PMID- 26367205 TI - Clinical Utilization of Repeated Open Application Test Among American Contact Dermatitis Society Members. AB - BACKGROUND: The repeated open application test (ROAT) provides useful information regarding allergens in suspected cases of allergic contact dermatitis; however, standardized methodology has not been established. OBJECTIVE: The aim of this study was to assess how ROAT is used in clinical and research settings. METHODS: We distributed a survey regarding ROAT practice to the American Contact Dermatitis Society and conducted a literature review of ROAT utilization in research. RESULTS: A total of 67 American Contact Dermatitis Society members participated in the survey. Respondents most frequently recommend application of leave-on products twice daily (46.0%) and rinse-off products once daily (43.5%). The most commonly used anatomical sites include the forearm (38.7%) and antecubital fossa (32.3%). Most respondents continue ROAT for 1 (49.2%) or 2 weeks (31.7%). Literature review of 32 studies (26 leave-on, 6 rinse-off) revealed that application frequency is most common at twice daily for both leave on (96.2%) and rinse-off (50.0%) products. The most common anatomical site is the forearm (62.5%), with an overall study duration of 3 to 4 weeks (65.6%). CONCLUSIONS: When comparing ROAT clinical and research practice, the majority trend was consistent for leave-on product application frequency and anatomical site, but not for rinse-off product application frequency, or overall duration. Further research is needed to determine best practice recommendations. PMID- 26367206 TI - Multicenter Patch Testing With a Resol Resin Based on Phenol and Formaldehyde Within the International Contact Dermatitis Research Group. AB - BACKGROUND: Contact allergy to phenol-formaldehyde resins (PFRs) based on phenol and formaldehyde is not detected by a p-tertiary-butylphenol-formaldehyde resin included in most baseline patch test series. OBJECTIVE: The aims of this study were to investigate the contact allergy rate to PFR-2 in an international population and to investigate associated simultaneous allergic reactions. METHODS: Thirteen centers representing the International Contact Dermatitis Research Group included PFR-2 into their patch test baseline series during a period of 6 months in 2012. RESULTS: Of 2259 patients tested, 28 (1.2%) reacted to PFR-2. Of those 28 individuals, one had a positive reaction to formaldehyde and 2 to p-tertiary-butylphenol-formaldehyde resin. Simultaneous allergic reactions were noted to colophonium in 3, to Myroxylon pereirae in 5, and to fragrance mix I in 8. CONCLUSIONS: The contact allergy frequency in the tested population (1.2%) merits its inclusion into the international baseline series and possibly also into other baseline series after appropriate investigations. Significantly, overrepresented simultaneous allergic reactions were noted for M. pereirae and fragrance mix I. PMID- 26367207 TI - Acrylate Systemic Contact Dermatitis. AB - Acrylates, the 2012 American Contact Dermatitis Society allergen of the year, are found in a range of products including the absorbent materials within feminine hygiene pads. When fully polymerized, acrylates are nonimmunogenic; however, if not completely cured, the monomers can be potent allergens.A 28-year-old woman is presented, who had her teeth varnished with Isodan (Septodont, Saint-Maur-des Fosses, France) containing HEMA (2-hydroxyethyl methacrylate) with no initial reaction. Approximately 1 month later, the patient developed a genital dermatitis secondary to her feminine hygiene pads. The initial reaction resolved, but 5 months later, the patient developed a systemic contact dermatitis after receiving a second varnishing.The patient was dramatically patch test positive to many acrylates. This case demonstrates a reaction to likely unpolymerized acrylates within a feminine hygiene pad, as well as broad cross-reactivity or cosensitivity to acrylates, and possibly a systemic contact dermatitis with systemic re exposure to unpolymerized acrylates. PMID- 26367208 TI - Protein Contact Dermatitis to Pig Semen. PMID- 26367209 TI - Systemic Contact Dermatitis due to Flaxseed Ingestion. PMID- 26367210 TI - The Utility of Patch Testing Methylisothiazolinone 2000 ppm aqua. PMID- 26367211 TI - WWSSF - a worldwide study on radioisotopic renal split function: reproducibility of renal split function assessment in children. AB - PURPOSE: The split or differential renal function is the most widely accepted quantitative parameter derived from radionuclide renography. To examine the intercenter variance of this parameter, we designed a worldwide round robin test. METHODS: Five selected dynamic renal studies have been distributed all over the world by e-mail. Three of these studies are anonymized patient data acquired using the EANM standardized protocol and two studies are phantom studies. In a simple form, individual participants were asked to measure renal split function as well as to provide additional information such as data analysis software, positioning of background region of interest, or the method of calculation. RESULTS: We received the evaluation forms from 34 centers located in 21 countries. The analysis of the round robin test yielded an overall z-score of 0.3 (a z-score below 1 reflecting a good result). However, the z-scores from several centers were unacceptably high, with values greater than 3. In particular, the studies with impaired renal function showed a wide variance. CONCLUSION: A wide variance in the split renal function was found in patients with impaired kidney function. This study indicates the ultimate importance of quality control and standardization of the measurement of the split renal function. It is especially important with respect to the commonly accepted threshold for significant change in split renal function by 10%. PMID- 26367212 TI - Increased 18F-FDG uptake suggests synovial inflammatory reaction with osteoarthritis: preliminary in-vivo results in humans. AB - OBJECTIVE: The aim of this prospective study was to compare the metabolic activity of the knee joints of a group of patients with painful knees clinically (such as recurrent joint pain, joint instability, and functional limitations) consistent with osteoarthritis and those of another group of patients without such complaints, using [F]-2-fluoro-2-deoxy-D-glucose (F-FDG)-PET imaging. METHODS: A total of 97 patients who participated in either painful joint prosthesis or diabetic foot research studies involving F-FDG-PET scans were asked to complete a knee pain questionnaire. The patients were asked whether they experienced pain in any joint, and if so, which joints were affected. RESULTS: A total of 18 knee joints without prosthesis were reported to be painful. The maximum standardized uptake values (SUVmax) of the middle joint space and lateral synovial tissue of these 18 knees were measured and compared with those of a set of patients with control asymptomatic knees. The average SUVmax of the middle part of the joint space in the painful knees was 1.35+/-0.59 compared with an average SUVmax value of 0.86+/-0.14 in the control group (P=0.0176). The average SUVmax of the synovium in the lateral part of the painful joints was 1.17+/-0.49 compared with 0.73+/-0.31 in the control group (P=0.0161). CONCLUSION: These data indicate that increased F-FDG uptake is associated with knee pain in osteoarthritis patients and that there is a positive relationship between the two parameters. PMID- 26367214 TI - Student Service Members/Veterans Participating in Higher Education: What We Know to Date. PMID- 26367213 TI - Comparison of characteristics of 18F-fluorodeoxyglucose and 18F-fluorothymidine PET during staging of esophageal squamous cell carcinoma. AB - OBJECTIVES: The aim of this study was to compare the characteristics derived from fluorine-18 fluorodeoxyglucose (F-FDG) and fluorine-18 fluorothymidine (F-FLT) PET quantitatively and to assess their capacities during staging of esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: Thirty-six patients with a diagnosis of ESCC who underwent both F-FDG and F-FLT PET were included in this study. Different image-derived indices including the standardized uptake value (SUV), gross tumor length, and texture features were determined. Considering histopathologic examination as the gold standard, the performance of the extracted indices during staging of ESCC was assessed using the Kruskal-Wallis test and the Mann-Whitney test. RESULTS: Considering the F-FDG PET images, the SUVmax, SUVmean, length (LEN), and eccentricity (EC) were significant during staging of American Joint Committee on Cancer (AJCC) and TNM (P<0.01), whereas for the F-FLT image, the SUVmax, LEN, and EC were significant during staging of AJCC and TNM (P<0.01). The characteristics of F-FDG and F-FLT PET for the classification of ESCC stage were significantly different. CONCLUSION: F-FDG image-derived characteristics including image textural features, SUV, and shape feature allow for better stratification of AJCC and TNM than F-FLT PET in ESCC patients. PMID- 26367215 TI - Readjustment of Urban Veterans: A Mental Health and Substance Use Profile of Iraq and Afghanistan Veterans in Higher Education. AB - OBJECTIVE: To identify the prevalence of substance use and mental health problems among veterans and student service members/veterans (SSM/V) returning from Iraq and Afghanistan to New York City's low-income neighborhoods. PARTICIPANTS: A sample of 122 veterans attending college and 116 veterans not enrolled recruited using respondent-driven sampling. METHODS: Logistic regression analysis of variation in characteristics of those veterans attending college; linear regression examining effects of college attendance on life satisfaction. RESULTS: Having a traumatic brain injury or disability was positively associated with college attendance. Being married, employed, or in college was predictive of overall life satisfaction. SSM/V were significantly less likely to screen positive for depression or drug use disorder. African American veterans were significantly less likely to attend college than white or Hispanic veterans. CONCLUSION: Substance use and some mental health disorders do not preclude inner city veterans from entering higher education. This study contributes to the sparse literature on African American veterans and SSM/V. PMID- 26367216 TI - Use of bone marrow-derived cells for regenerative medicine in Cuba. PMID- 26367217 TI - A randomized study of melphalan 200 mg/m(2) vs 280 mg/m(2) as a preparative regimen for patients with multiple myeloma undergoing auto-SCT. AB - We aimed to examine whether doses of melphalan higher than 200 mg/m(2) improve response rates when used as conditioning before autologous transplant (ASCT) in multiple myeloma (MM) patients. Patients with MM, n=131, were randomized to 200 mg/m(2) (mel200) vs 280 mg/m(2) (mel280) using amifostine pretreatment. The primary end point was the proportion of patients achieving near complete response (?nCR). No treatment-related deaths occurred in this study. Responses following ASCT were for mel200 vs mel280, respectively, ?nCR 22 vs 39%, P=0.03, ?PR 57 vs 74%, P=0.04. The hazard of mortality was not statistically significantly different between groups (mel200 vs mel280; hazard ratio (HR)=1.15 (95% confidence interval (CI), 0.62-2.13, P=0.66)) nor was the rate of progression/mortality (HR=0.81 (0.52-1.27, P=0.36)). The estimated PFS at 1 and 3 years were 83 and 46%, respectively, for mel200 and 78 and 54%, respectively, for mel280. Amifostine and mel280 were well tolerated, with no grade 4 regimen related toxicities and only one grade 3 mucositis (none with mel200) and three grade 3 gastrointestinal (GI) toxicities (two in mel200). Hospitalization rates were more frequent in the mel280 group (59 vs 43%, P=0.08). Mel280 resulted in a higher major response rate (CR+nCR) and should be evaluated in larger studies. PMID- 26367218 TI - Prevalence, predictors and outcomes of cardiopulmonary resuscitation in hospitalized adult stem cell transplant recipients in the United States: not just opening the black box but exploring an opportunity to optimize! PMID- 26367219 TI - Allogeneic stem cell transplantation (allo-SCT) for de novo Ph+ AML: a study from the French Society of Bone Marrow Transplantation and Cell Therapy. PMID- 26367220 TI - Cellular engineering and therapy in combination with cord blood allografting in pediatric recipients. AB - Cord blood (CB) transplantation is an alternate source of human hematopoietic progenitor cells for allogeneic stem cell transplantation in children and adolescents with both malignant and nonmalignant diseases. Current limitations included delay in hematopoietic reconstitution, increased incidence of primary graft failure and slow cellular immunoreconstitution. These limitations lead to a significant increase in primary graft failure, infectious complications and increased transplant-related mortality. There is a number of experimental approaches currently under investigation including cellular engineering to circumvent these limitations. In this review, we summarize the recent findings of utilizing ex vivo CB expansion with Notch1 ligand Delta 1, mesenchymal progenitor cells, the use of human placenta-derived stem cells and CB-derived natural killer cells. Early and preliminary results suggest some of these experimental cellular strategies may in part ameliorate the incidence of primary graft failure, delays in hematopoietic reconstitution and/or slowness in cellular immune reconstitution following unrelated CB transplantation. PMID- 26367222 TI - Survival of patients who develop solid tumors following hematopoietic stem cell transplantation. AB - Allogeneic hematopoietic cell transplantation is associated with late adverse effects of therapy, including secondary solid cancers. Most reports address risk factors; however, outcomes after secondary solid cancer development are incompletely described. Our objective was to estimate survival probabilities for transplant recipients dependent on secondary solid cancer subtype. We used a previously identified and published cohort who developed secondary solid cancers following allogeneic transplant. Follow-up for these 112 previously identified patients was extended and their survival probabilities were studied. Median duration of follow-up from the development of secondary cancer for survivors was 11.9 years (range: 0.8-23.4) and 75% were followed >7.0 years. The 5- and 10-year overall survival probabilities were 50% (95% confidence interval (CI): 41-60) and 46% (95% CI: 37-57), respectively. Overall survival varied by secondary cancer type. Secondary cancer was the cause of death in most patients who died following development of melanoma, central nervous system, oral cavity, thyroid, lung, lower gastrointestinal tract and bone cancers. Extended follow-up allowed for the most comprehensive longitudinal evaluation to date of this rare condition. These findings will enhance clinicians' ability to predict outcomes and counsel transplant survivors who develop secondary solid cancers. PMID- 26367221 TI - Second allogeneic transplantation for relapse of malignant disease: retrospective analysis of outcome and predictive factors by the EBMT. AB - In patients treated with allogeneic stem cell transplantation (SCT) for malignant disease who suffer from a relapse after the transplantation, the role of second allogeneic SCT is often uncertain. In a retrospective analysis, 2632 second allogeneic transplantations carried out for a relapse after the first transplantation were analyzed to define indications and identify predictive factors. Fifteen percent of the patients remained relapse-free until 5 years after the second SCT. Patients with CML had a better survival than patients with other diseases. In a multivariate analysis, factors associated with better survival were low disease burden, longer remission duration after the first transplantation, longer interval between the transplantations, younger age, absence of grade II-IV acute GvHD or chronic GvHD after the first transplantation, and later year of transplantation. The European Society for Blood and Marrow Transplantation risk score predicted the outcome. Using the same donor as in the first transplantation vs another donor had no predictive value for survival. Sibling donor was a favorable predictive factor. In conclusion, second allogeneic SCT offers a reasonable option especially for young patients with a long remission after the first transplantation and a low disease burden. The present findings do not support the usefulness of changing the donor for the second transplantation. PMID- 26367223 TI - Continuous IV infusion of MESNA can prevent hemorrhagic cystitis in HSCT and retain MESNA concentration in urine. PMID- 26367224 TI - Treatment with novel RSV Ig RI-002 controls viral replication and reduces pulmonary damage in immunocompromised Sigmodon hispidus. AB - Respiratory syncytial virus (RSV) is a significant cause of bronchiolitis and pneumonia in several high health risk populations, including infants, elderly and immunocompromised individuals. Mortality in hematopoietic stem cell transplant recipients with lower respiratory tract RSV infection can exceed 80%. It has been shown that RSV replication in immunosuppressed individuals is significantly prolonged, but the contribution of pulmonary damage, if any, to the pathogenesis of RSV disease in this susceptible population is not known. In this work, we tested RI-002, a novel standardized Ig formulation containing a high level of RSV neutralizing Ab, for its ability to control RSV infection in immunocompromised cotton rats Sigmodon hispidus. Animals immunosuppressed by repeat cyclophosphamide injections were infected with RSV and treated with RI-002. Prolonged RSV replication, characteristic of immunosuppressed cotton rats, was inhibited by RI-002 administration. Ab treatment reduced detection of systemic dissemination of viral RNA. Importantly, pulmonary interstitial inflammation and epithelial hyperplasia that were significantly elevated in immunosuppressed animals were reduced by RI-002 administration. These results indicate the potential of RI-002 to improve outcome of RSV infection in immunocompromised subjects not only by controlling viral replication, but also by reducing damage to lung parenchyma and epithelial airway lining, but further studies are needed. PMID- 26367226 TI - Transmission of CML or of t(9; 22) and BCR/ABL? They are not the same. PMID- 26367225 TI - Identification and validation of biomarkers associated with acute and chronic graft versus host disease. AB - Graft versus host disease (GVHD) is a major complication of haematopoietic SCT (HSCT). A number of inflammatory cytokines/chemokines are implicated in GVHD and have been identified in numerous single centre studies as potential biomarkers for acute and/or chronic GVHD. In this study, we analysed candidate inflammatory biomarkers (B-cell activating factor (BAFF), interleukin 33 (IL-33), CXCL10 and CXCL11) in a two-centre study. Biomarkers were evaluated pre-transplant and at serial time points post transplant in acute and chronic GVHD patient sera with time-matched control samples from patients without GVHD. Further validation was performed using the human skin explant assay, clinical GVHD biopsies and mRNA expression analysis. BAFF was significantly increased pre-transplant. BAFF, IL 33, CXCL10 and CXCL11 showed increased levels in acute GVHD patient sera and high protein expression in grades II-III of the in vitro skin explant graft versus host reaction (GVHR) group. BAFF, CXCL10 and CXCL11 also showed increased mRNA expression levels in clinical biopsies compared with the no/low-grade GVHD group. BAFF, CXCL10 and CXCL11 levels were increased in chronic GVHD patient sera. The results identify BAFF and CXCL10 as predictive biomarkers for acute GVHD and BAFF, CXCL10 and CXCL11 as useful diagnostic biomarkers for acute GVHD and chronic GVHD. PMID- 26367227 TI - Dirk W van Bekkum 1925-2015. PMID- 26367228 TI - Sirolimus-related anal ulceration in a female patient after allogeneic stem cell transplantation. PMID- 26367229 TI - A prospective investigation of cell dose in single-unit umbilical cord blood transplantation for adults with high-risk hematologic malignancies. AB - Umbilical cord blood (UCB) as an allogeneic transplant source is generally limited to units with pre-cryopreservation total nucleated cell (TNC) doses ?2.5 * 10(7) NC/kg. We prospectively investigated single UCB transplantation, with cord units as low as 1 * 10(7) NC/kg, all processed with post-thaw albumin dextran dilution. We transplanted 104 adult patients with 84% having relapsed/refractory disease. The median TNC dose was 2.1 * 10(7) NC/kg (range: 1.0-4.4 * 10(7)) and median CD34+ cell dose was 1.0 * 10(5)/kg (range: 0.0-3.7 * 10(5)/kg). Post-manipulation cell recovery and viability were 96% and 99%, respectively. Median times to neutrophil and platelet engraftment were 16 and 43 days, respectively. Univariate factors predicting neutrophil engraftment included TNC (P=0.03) and CD34+ cell dose (P=0.01). CD34+ dose predicted platelet engraftment (P<0.001). In multivariate analysis, CD34+ dose remained significant for neutrophil and platelet engraftment (P<0.0001 and P<0.0001, respectively). The 100-day and 1-year overall survival were 70% and 46%, respectively (95% confidence interval: 36%-56% at 1 year). The subset transplanted with 1-1.5 * 10(7) NC/kg had similar 100-day and 1-year survivals of 73% and 45%, respectively. Single-unit UCB transplantation using small units, processed as described, leads to favorable engraftment and acceptable outcomes in poor prognosis patients. CD34+ cell dose (?1.5 * 10(5)/kg) helps predict faster engraftment and can aid in graft selection. PMID- 26367231 TI - Partial depletion of TCR alpha/beta(+)/ CD19(+) cells in matched unrelated transplantation of three patients with osteopetrosis. PMID- 26367230 TI - Risk factors and prognosis of hepatic acute GvHD after allogeneic hematopoietic cell transplantation. AB - Hepatic acute GvHD (aGvHD) is associated with high mortality owing to poor response to immunosuppressive therapy. The pathogenesis of hepatic aGvHD differs from that of other lesions, and specific risk factors related to pre-transplant liver conditions should be determined. We conducted a cohort study by using a Japanese transplant registry database (N=8378). Of these subjects, 1.5% had hepatitis C virus Ab (HCV-Ab) and 9.4% had liver dysfunction (elevated transaminase or bilirubin levels) before hematopoietic cell transplantation (HCT). After HCT, the cumulative incidence of hepatic aGvHD was 6.7%. On multivariate analyses, HCV-Ab positivity (hazard ratio (HR), 1.93; P=0.02) and pre-transplant liver dysfunction (HR, 1.85; P<0.01), as well as advanced HCT risk, unrelated donors, HLA mismatch and cyclosporine as GvHD prophylaxis, were significant risk factors for hepatic aGvHD, whereas hepatitis B virus surface Ag was not. Hepatic aGvHD was a significant risk factor for low overall survival and high transplant-related mortality in all aGvHD grades (P<0.01). This study is the first to show the relationship between pre-transplant liver conditions and hepatic aGvHD. A prospective study is awaited to validate the results of this study and establish a new strategy especially for high-risk patients. PMID- 26367232 TI - Anicteric veno-occlusive disease after hematopoietic stem cell transplantation in children. PMID- 26367234 TI - UGT2B17 minor histocompatibility mismatch and clinical outcome after HLA identical sibling donor stem cell transplantation. AB - Minor histocompatibility Ags (mHags) have been implicated in the pathogenesis of GVHD after allogeneic hematopoietic stem cell transplantation (HSCT). Uridine diphospho-glucuronosyltransferase 2B17 (UGT2B17) gene deletion may act as a mHag and its association with acute GVHD (aGVHD) has been described. We retrospectively studied the clinical impact of a UGT2B17 mismatch in a cohort of 1127 patients receiving a HSCT from an HLA-identical sibling donor. UGT2B17 mismatch was present in 69 cases (6.1%). Incidence of severe aGVHD was higher in the UGT2B17 mismatched pairs (22.7% vs 14.6%), but this difference was not statistically significant (P: 0.098). We did not detect differences in chronic GVHD, overall survival, relapse-free survival, transplant-related mortality or relapse. Nevertheless, when we analyzed only those patients receiving grafts from a male donor (616 cases), aGVHD was significantly higher in the UGT2B17 mismatched group (25.1% vs 12.8%; P: 0.005) and this association was confirmed by the multivariate analysis (P: 0.043; hazard ratio: 2.16, 95% confidence interval: 1.03-4.57). Overall survival was worse for patients mismatched for UGT2B17 (P: 0.005). We conclude that UGT2B17 mismatch has a negative clinical impact in allogeneic HSCT from HLA-identical sibling donors only when a male donor is used. These results should be confirmed by other studies. PMID- 26367233 TI - Physical function and quality of life in patients with chronic GvHD: a summary of preclinical and clinical studies and a call for exercise intervention trials in patients. AB - Allogeneic hematopoietic stem cell transplant, to reconstitute the hematopoietic and immune status of patients undergoing myeloablative therapy for hematologic disorders, has been of great benefit in minimizing or eradicating disease and extending survival. Patients who undergo allogeneic hematopoietic stem cell transplant (allo-HSCT) are subject to many comorbidities among which the most significant, affecting quality of life (QoL) and survival, are acute GvHD (aGvHD) and chronic GvHD (cGvHD), resulting from donor lymphocytes reacting to and damaging host tissues. Physical activity and exercise have clearly been shown, in both children and adults, to enhance fitness, improve symptomatology and QoL, reduce disease progression and extend survival for many diseases including malignancies. In some cases, vigorous exercise has been shown to be equal to or more effective than pharmacologic therapy. This review addresses how cGvHD affects patients' physical function and physical domain of QoL, and the potential benefits of exercise interventions along with recommendations for relevant research and evaluation targeted at incorporating this strategy as soon as possible after allo-HSCT and ideally, as soon as possible upon diagnosis of the condition leading to allo-HSCT. PMID- 26367235 TI - Next-generation long-term transplant clinics: improving resource utilization and the quality of care through health information technology. AB - By the year 2020, potentially one-half a million hematopoietic cell transplant (HCT) recipients will need long-term follow-up care to address not only chronic GvHD but also multiple other late consequences of transplant. Despite this increase in patients, there will not be a concomitant increase in the HCT workforce. Thus, the future of long-term patient management will require a new 'next-generation' clinical model that utilizes technological solutions to make the care of the HCT patient efficient, safe and cost-effective. Guideline-based decision support will be embedded in clinical workflows. Documentation requirements will be reduced as automated data collection from electronic medical records (EMRs) will populate registries and provide feedback for a rapid learning health system. Interoperable EMRs will disseminate treatment protocols to multiple care providers in a distributed long-term clinic model, such that providers outside of the transplant center can provide services closer to the patient. Patients will increase their participatory role through patient portals and mobile devices. At Vanderbilt, we have responded to some of these future challenges by embedding guideline-based decision support, structuring clinical documentation and being early adopters of communication technology. This manuscript describes the current state of some of these innovations, and a vision for the future of the long-term transplant clinic. PMID- 26367236 TI - Allogeneic stem cell transplantation after conditioning with treosulfan, etoposide and cyclophosphamide for patients with ALL: a phase II-study on behalf of the German Cooperative Transplant Study Group and ALL Study Group (GMALL). AB - TBI-based preparative regimens are considered as standard conditioning therapy for allogeneic stem cell transplantation (AHSC) in patients with ALL. We investigated toxicity and efficacy of a non-TBI-based regimen consisting of treosulfan, etoposide and cyclophosphamide for ALL within a prospective study. Major inclusion criteria were CR and non-eligibility for TBI. Fifty patients with a median age of 46.5 years (range, 18-64) were included. Donors were HLA identical sibling (n=8), matched (n=42) or mismatched (n=10) unrelated. The toxicity was moderate, resulting in a cumulative incidence of non-relapse mortality (NRM) at 1 year of 8% (90% confidence interval: 2-15%). Acute GvHD grade II-IV and grade III/IV was noted in 53% and 14%, respectively. Chronic GvHD at one year was seen in 41%. After a median follow-up of 24 months the cumulative incidence of relapse was 36% (90% confidence interval: 24-48) and 51% (90% confidence interval: 37-65) at 1 and 2 years, respectively. The estimated 2-year disease-free and overall survivals were 36 and 48%, respectively. Treosulfan, etoposide and cyclophosphamide followed by AHSC has a favorable toxicity profile with low NRM and therefore represents a potential alternative regimen for ALL in 1. CR (NCT00682305). PMID- 26367238 TI - Efficacy and safety of deferasirox in non-thalassemic patients with elevated ferritin levels after allogeneic hematopoietic stem cell transplantation. AB - Elevated serum ferritin contributes to treatment-related morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). The multicenter DE02 trial assessed the safety, efficacy and impact of deferasirox on iron homeostasis after allogeneic HSCT. Deferasirox was administered at a starting dose of 10 mg/kg per day to 76 recipients of allogeneic HSCT, with subsequent dose adjustments based on efficacy and safety. Deferasirox was initiated at a median of 168 days after HSCT, with 84% of patients still on immunosuppression. Baseline serum ferritin declined from 2045 to 957 ng/mL. Deferasirox induced a negative iron balance in 84% of patients. Hemoglobin increased in the first 3 months, and trough serum cyclosporine levels were stable. Median exposure was 330 days, with a median compliance rate of >80%. The most common investigator reported drug-related adverse events (AEs) were increased blood creatinine (26.5%), nausea (9.0%) and abdominal discomfort (8.3%). Fifty-four (71.1%) patients experienced drug-related AEs, which occasionally resulted in discontinuation (gastrointestinal (n=6), skin (n=3), elevated transaminases (n=1) and creatinine (n=1)). The incidence of AEs appeared to be dose related, with 7.5 mg/kg per day being the best-tolerated dose. Low-dose deferasirox is an effective chelation therapy after allogeneic HSCT, with a manageable safety profile, even in patients receiving cyclosporine. PMID- 26367237 TI - In patients older than 55 years with AML in first CR, should we search for a matched unrelated donor when an old sibling donor is available? AB - Allogeneic hematopoietic transplantation is increasingly used in patients aged 55 years or more with AML. The question of whether outcomes can be improved with an allele-level 8/8 HLA-matched unrelated donor (MUD) rather than an older HLA matched sibling (MSD, more than 55 years) is still unanswered. We thus analyzed outcomes in 714 patients aged 55 years and older with AML in first CR (CR1) who received PBSCs after a reduced-intensity conditioning hematopoietic cell transplant from a MUD (n=310) or a MSD (n=404) in a recent period (2005-2010). The 3-year cumulative incidences (CIs) of non-relapse mortality were 17% and 23% with MSD and MUD, respectively (P=0.17). The 3-year CIs of relapse were 37% and 30%, respectively (P=0.12), resulting in a 3-year CI of leukemia-free survival of 46% and 47%, respectively (P=0.51). The 3-year overall survival was 49% with both MSD and MUD. In conclusion, HLA-identical sibling donors aged 55 years or more should not be excluded because of age for patients aged 55 years and older with AML in CR1. PMID- 26367239 TI - Outcome of patients with relapsed diffuse large B-cell lymphoma who fail second line salvage regimens in the International CORAL study. AB - Salvage chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard second-line treatment for relapsed and refractory diffuse large B cell lymphoma (DLBCL). However, the strategy is less clear in patients who require third-line treatment. Updated outcomes of 203 patients who could not proceed to scheduled ASCT in the Collaborative Trial in Relapsed Aggressive Lymphoma (CORAL) are herein reviewed. In the intent-to-treat analysis, overall response rate to third-line chemotherapy was 39%, with 27% CR or CR unconfirmed, and 12% PR. Among the 203 patients, 64 (31.5%) were eventually transplanted (ASCT 56, allogeneic SCT 8). Median overall survival (OS) of the entire population was 4.4 months. OS was significantly improved in patients with lower tertiary International Prognostic Index (IPI), patients responding to third-line treatment and patients transplanted with a 1-year OS of 41.6% compared with 16.3% for the not transplanted (P<0.0001). In multivariate analysis, IPI at relapse (hazard ratio (HR) 2.409) and transplantation (HR 0.375) independently predicted OS. Third-line salvage chemotherapy can lead to response followed by transplantation and long-term survival in DLBCL patients. However, improvement of salvage efficacy is an urgent need with new drugs. PMID- 26367240 TI - The prevalence of asthma risk and contributing factors in underserved Vietnamese children in Orange County, CA. AB - OBJECTIVES: Vietnamese constitutes one of the fastest growing minority groups in America, with the largest concentration in Orange County (OC), CA. Yet, there are limited data on the prevalence of asthma in Vietnamese children. Our study evaluated the risk of asthma and key contributing factors among these children living in OC, CA. METHOD: Five elementary schools in OC that were predominantly Vietnamese with low socioeconomic status were selected for participation. Validated surveys were sent to parents of all students ages 3-12 in these schools with materials available in English, Vietnamese and Spanish. Surveys included questions to identify the risk of asthma and related key factors. Surveys were completed by parents and returned to schools. RESULTS: There were 1530 participants eligible for analysis. Asthma risk was 30.4%, and of these, 22.6% had no prior diagnosis. Contributing factors to identification of those at risk were male gender (p < 0.001), preferred use of the Vietnamese language (p = 0.004), longer duration in the United States (p = 0.019), and smoker in the household (p = 0.015). CONCLUSIONS: The prevalence of asthma risk in our community of low socioeconomic status Vietnamese children was found to be higher than commonly appreciated. Furthermore, a considerable number of these children had not been previously diagnosed. Given the limited information in this population, our current findings of asthma risk and key contributing factors could affect health care policies that allow appropriate funding for programs dedicated to asthma care in this and other growing population. PMID- 26367241 TI - Tomato I2 Immune Receptor Can Be Engineered to Confer Partial Resistance to the Oomycete Phytophthora infestans in Addition to the Fungus Fusarium oxysporum. AB - Plants and animals rely on immune receptors, known as nucleotide-binding domain and leucine-rich repeat (NLR)-containing proteins, to defend against invading pathogens and activate immune responses. How NLR receptors respond to pathogens is inadequately understood. We previously reported single-residue mutations that expand the response of the potato immune receptor R3a to AVR3a(EM), a stealthy effector from the late blight oomycete pathogen Phytophthora infestans. I2, another NLR that mediates resistance to the will-causing fungus Fusarium oxysporum f. sp. lycopersici, is the tomato ortholog of R3a. We transferred previously identified R3a mutations to I2 to assess the degree to which the resulting I2 mutants have an altered response. We discovered that wild-type I2 protein responds weakly to AVR3a. One mutant in the N-terminal coiled-coil domain, I2(I141N), appeared sensitized and displayed markedly increased response to AVR3a. Remarkably, I2(I141N) conferred partial resistance to P. infestans. Further, I2(I141N) has an expanded response spectrum to F. oxysporum f. sp. lycopersici effectors compared with the wild-type I2 protein. Our results suggest that synthetic immune receptors can be engineered to confer resistance to phylogenetically divergent pathogens and indicate that knowledge gathered for one NLR could be exploited to improve NLR from other plant species. PMID- 26367243 TI - Molecular detection and point-of-care testing in Ebola virus disease and other threats: a new global public health framework to stop outbreaks. AB - Ultrahigh sensitivity and specificity assays that detect Ebola virus disease or other highly contagious and deadly diseases quickly and successfully upstream in Spatial Care PathsTM can stop outbreaks from escalating into devastating epidemics ravaging communities locally and countries globally. Even had the WHO and CDC responded more quickly and not misjudged the dissemination of Ebola in West Africa and other world regions, mobile rapid diagnostics were, and still are, not readily available for immediate and definitive diagnosis, a stunning strategic flaw that needs correcting worldwide. This article strategizes point-of care testing for diagnosis, triage, monitoring, recovery and stopping outbreaks in the USA and other countries; reviews Ebola molecular diagnostics, summarizes USA FDA emergency use authorizations and documents why they should not be stop gaps; and reduces community risk from internal and external infectious disease threats by enabling public health at points of need. PMID- 26367242 TI - Characterization of the platelet transcriptome by RNA sequencing in patients with acute myocardial infarction. AB - Transcripts in platelets are largely produced in precursor megakaryocytes but remain physiologically active as platelets translate RNAs and regulate protein/RNA levels. Recent studies using transcriptome sequencing (RNA-seq) characterized the platelet transcriptome in limited number of non-diseased individuals. Here, we expand upon these RNA-seq studies by completing RNA-seq in platelets from 32 patients with acute myocardial infarction (MI). Our goals were to characterize the platelet transcriptome using a population of patients with acute MI and relate gene expression to platelet aggregation measures and ST segment elevation MI (STEMI) (n = 16) vs. non-STEMI (NSTEMI) (n = 16) subtypes. Similar to other studies, we detected 9565 expressed transcripts, including several known platelet-enriched markers (e.g. PPBP, OST4). Our RNA-seq data strongly correlated with independently ascertained platelet expression data and showed enrichment for platelet-related pathways (e.g. wound response, hemostasis, and platelet activation), as well as actin-related and post-transcriptional processes. Several transcripts displayed suggestively higher (FBXL4, ECHDC3, KCNE1, TAOK2, AURKB, ERG, and FKBP5) and lower (MIAT, PVRL3, and PZP) expression in STEMI platelets compared to NSTEMI. We also identified transcripts correlated with platelet aggregation to TRAP (ATP6V1G2, SLC2A3), collagen (CEACAM1, ITGA2), and ADP (PDGFB, PDGFC, ST3GAL6). Our study adds to current platelet gene expression resources by providing transcriptome-wide analyses in platelets isolated from patients with acute MI. In concert with prior studies, we identify various genes for further study in regards to platelet function and acute MI. Future platelet RNA-seq studies examining more diverse sets of healthy and diseased samples will add to our understanding of platelet thrombotic and non thrombotic functions. PMID- 26367245 TI - Use of FDG PET/CT in Patients with Pancoast Tumors: Does It Add Any Contribution to Patient Management? AB - PURPOSE: To evaluate any potential value of 2-deoxy-2-[18F] fluoro-D-glucose with positron emission tomography/computerized tomography (FDG PET/CT) in staging of patients with Pancoast tumors and to investigate the relationship between volume based quantitative PET parameters and prognosis. MATERIALS AND METHODS: The authors retrospectively reviewed data of the 47 patients with Pancoast tumors who underwent initial staging by conventional imaging methods and FDG PET/CT. FDG-PET images were visually and quantitatively evaluated, and metabolic tumor volume (MTV), total lesion glycolysis, and maximum standardized uptake values of primary tumors were calculated. The correlations between quantitative PET parameters and tumor stages, as well as overall survival, were analyzed. RESULTS: By detecting unknown distant metastasis, PET/CT upstaged 21% of patients. The sensitivity and specificity for detection of lymphatic involvement were 100% and 83.75%, respectively. Having surgery (p = 0.01) and being at an early stage (p = 0.004) were the most predictive factors for overall survival. Although there was no significant correlation between quantitative PET parameters and overall survival, MTV was the most powerful discriminator for operability and preoperative staging (p < 0.05). CONCLUSIONS: FDG-PET imaging was found to be a valuable method for an accurate staging in the management of patients with Pancoast tumor. Having surgery and being at an early stage at presentation were found to be significant predictors for survival. Quantitative metabolic parameters may contribute to clarification of operable patient subgroups having an early disease stage with low MTV. PMID- 26367246 TI - Family-Centered Care and High-Consequence Pathogens: Thinking Outside the Room. PMID- 26367244 TI - Combining anaerobic bacterial oncolysis with vaccination that blocks interleukin 10 signaling may achieve better outcomes for late stage cancer management. AB - Late stage solid tumors cause significant cancer mortality rates worldwide and effective therapy remains a big challenge. Cancer therapeutic vaccines elicit tumor specific T cells that kill tumor cells yet often fail to result in tumor destruction because of the limited T cell response and the local immune suppressive environment. Blocking interleukin 10 (IL-10) signaling at the time of therapeutic vaccination elicits much stronger T cell responses than vaccination without IL-10 blocking. Anaerobic oncolytic bacteria target hypoxic regions of the late stage tumor tissues which not only stops tumor growth but also provides a pro-inflammatory environment that may increase the effectiveness of a therapeutic vaccine by recruiting more effector T cells to tumor site. In this review, we argue that combining both bacterial and vaccine therapies may improve the efficiency of late stage cancer management. PMID- 26367247 TI - Polymer Adsorption on Graphite and CVD Graphene Surfaces Studied by Surface Specific Vibrational Spectroscopy. AB - Sum-frequency vibrational spectroscopy was employed to probe polymer contaminants on chemical vapor deposition (CVD) graphene and to study alkane and polyethylene (PE) adsorption on graphite. In comparing the spectra from the two surfaces, it was found that the contaminants on CVD graphene must be long-chain alkane or PE like molecules. PE adsorption from solution on the honeycomb surface results in a self-assembled ordered monolayer with the C-C skeleton plane perpendicular to the surface and an adsorption free energy of ~42 kJ/mol for PE(H(CH2CH2)nH) with n ~ 60. Such large adsorption energy is responsible for the easy contamination of CVD graphene by impurity in the polymer during standard transfer processes. Contamination can be minimized with the use of purified polymers free of PE-like impurities. PMID- 26367248 TI - miR-128 represses L1 retrotransposition by binding directly to L1 RNA. AB - Long interspersed element 1 (LINE-1 or L1) retrotransposons compose 17% of the human genome. Active L1 elements are capable of replicative transposition (mobilization) and can act as drivers of genetic diversity. However, this mobilization is mutagenic and may be detrimental to the host, and therefore it is under strict control. Somatic cells usually silence L1 activity by DNA methylation of the L1 promoter. In hypomethylated cells, such as cancer cells and induced pluripotent stem cells (iPSCs), a window of opportunity for L1 reactivation emerges, and with it comes an increased risk of genomic instability and tumorigenesis. Here we show that miR-128 represses new retrotransposition events in human cancer cells and iPSCs by binding directly to L1 RNA. Thus, we have identified and characterized a new function of microRNAs: mediating genomic stability by suppressing the mobility of endogenous retrotransposons. PMID- 26367250 TI - Effects of different self-assembled monolayers on thin-film morphology: a combined DFT/MD simulation protocol. AB - Organic thin film transistors (OTFTs) are multilayer field-effect transistors that employ an organic conjugated material as semiconductor. Several experimental groups have recently demonstrated that the insertion of an organic self-assembled monolayer (SAM) between the dielectric and the semiconductive layer is responsible for a sensible improvement of the OTFT performances in terms of an increased charge carrier mobility caused by a higher degree of order in the organic semiconductor layer. Here, we describe a combined periodic density functional theory (DFT) and classical molecular dynamics (MD) protocol applied to four different SAMs and a pentacene monolayer deposited onto their surfaces. In particular, we investigate the morphology and the surface of the four SAMs and the translational, orientational, and nematic order of the monolayer through the calculation of several distribution functions and order parameters pointing out the differences among the systems and relating them to known experimental results. Our calculations also suggest that small differences in the SAM molecular design will produce remarkable differences in the SAM surface and monolayer order. In particular, our simulations explain how a SAM with a bulky terminal group results in an irregular and rough surface that determines the deposition of a disordered semiconductive monolayer. On the contrary, SAMs with a small terminal group generate smooth surfaces with uninterrupted periodicity, thus favoring the formation of an ordered pentacene monolayer that increases the mobility of charge carriers and improves the overall performances of the OTFT devices. Our results clearly point out that the in silico procedure presented here might be of help in tuning the design of SAMs in order to improve the quality of OTFT devices. PMID- 26367251 TI - Celebrating Soft Matter's 10th Anniversary: Sequential phase transitions in thermoresponsive nanoemulsions. AB - We report the coexistence of stress-bearing percolation with arrested phase separation in a colloidal system of thermoresponsive nanoemulsions spanning a broad range of volume fractions (0.10 <= phi <= 0.33) and temperatures (22 degrees C <= T <= 65 degrees C). Here, gelation is driven by short-range interdroplet polymer bridging at elevated temperatures. Direct visualization of the gel microstructure shows that nanoemulsions undergo a homogenous percolation transition prior to phase separation. Rheological characterization shows that both the percolated and the phase separated structures are capable of supporting a significant amount of elastic stress. As the system is heated, the sequential onset of these phase transitions is responsible for the unusual two-step increase in the linear viscoelasticity of the gels. In addition, we find that slowing the heating rate significantly reduces the elasticity of the gels at high temperatures. Our results suggest that the formation of metastable gelled states not only depends on the attraction strength and volume fraction of the system, but is also sensitive to the rate at which the attraction strength is increased. PMID- 26367249 TI - Structure of a prokaryotic fumarate transporter reveals the architecture of the SLC26 family. AB - The SLC26 family of membrane proteins combines a variety of functions within a conserved molecular scaffold. Its members, besides coupled anion transporters and channels, include the motor protein Prestin, which confers electromotility to cochlear outer hair cells. To gain insight into the architecture of this protein family, we characterized the structure and function of SLC26Dg, a facilitator of proton-coupled fumarate symport, from the bacterium Deinococcus geothermalis. Its modular structure combines a transmembrane unit and a cytoplasmic STAS domain. The membrane-inserted domain consists of two intertwined inverted repeats of seven transmembrane segments each and resembles the fold of the unrelated transporter UraA. It shows an inward-facing, ligand-free conformation with a potential substrate-binding site at the interface between two helix termini at the center of the membrane. This structure defines the common framework for the diverse functional behavior of the SLC26 family. PMID- 26367252 TI - Development of an acetylcholinesterase-choline oxidase based biosensor for acetylcholine determination. AB - In this article, a novel amperometric acetylcholine (ACh) biosensor with immobilization of acetylcholinesterase-choline oxidase (AChE-ChO) on electrochemically polymerized polyaniline-polyvinylsulphonate (PANI-PVS) film has been successfully developed for the first time. AChE and ChO enzymes were immobilized on PANI-PVS film by cross-linking with using glutaraldehyde (GA) and bovine serum albumin (BSA). Determination of ACh was carried out by oxidation of enzymatically produced H2O2 at +0.4 V versus Ag/AgCl. Optimum pH and temperature were found to be 8.0 and 60 degrees C, respectively. The linear part was in the region 1.0 * 10(-7)-6.0 * 10(-7) M (R(2) = 0.990). Storage stability and operation stability of the enzyme electrode were also studied. PMID- 26367253 TI - Aptamer loaded MoS2 nanoplates as nanoprobes for detection of intracellular ATP and controllable photodynamic therapy. AB - In this work we designed a MoS2 nanoplate-based nanoprobe for fluorescence imaging of intracellular ATP and photodynamic therapy (PDT) via ATP-mediated controllable release of (1)O2. The nanoprobe was prepared by simply assembling a chlorine e6 (Ce6) labelled ATP aptamer on MoS2 nanoplates, which have favorable biocompatibility, unusual surface-area-to-mass ratio, strong affinity to single stranded DNA, and can quench the fluorescence of Ce6. After the nanoprobe was internalized into the cells and entered ATP-abundant lysosomes, its recognition to ATP led to the release of the single-stranded aptamer from MoS2 nanoplates and thus recovered the fluorescence of Ce6 at an excitation wavelength of 633 nm, which produced a highly sensitive and selective method for imaging of intracellular ATP. Meanwhile, the ATP-mediated release led to the generation of (1)O2 under 660 nm laser irradiation, which could induce tumor cell death with a lysosomal pathway. The controllable PDT provided a model approach for design of multifunctional theranostic nanoprobes. These results also promoted the development and application of MoS2 nanoplate-based platforms in biomedicine. PMID- 26367256 TI - Problems and Challenges Linked to Bilateral Vestibular Deficits. PMID- 26367254 TI - Paraumbilical perforator flap for reconstruction of the external auditory meatus: A case report. AB - We herein present a technique of using the umbilical stalk for reconstruction of the external auditory meatus. A 49-year-old female presented with locally aggressive melanoma affecting her mastoid region. She underwent radical excision including the skin and soft tissues around the external ear with simultaneous lymph node clearance. The resultant defect measured 15 cm * 8 cm in diameter and was 2.5 cm deep. This was reconstructed with a similarly sized microvascular paraumbilical perforator flap that included the umbilical stalk. In the post operative course there was complete flap survival but a prolonged wound dehiscence near the auditory meatus that required revision surgery. At 15-months follow-up, the patient was melanoma-free and the auditory meatus was patent. Hearing was also preserved. The umbilical stalk is one of the few skin covered tubed structures in the human body that may be used without major donor morbidity to "replace like with like," the auditory channel. PMID- 26367257 TI - Previous Cancer/Lymphoma and Refractory Inflammatory Bowel Disease. AB - Immunomodulators and biologic agents are effective in treating inflammatory bowel diseases (IBDs), and recent evidence supports their introduction earlier in the disease course. An important concern to both patients and physicians considering immunosuppression (IS) for the treatment of IBD is the potential associated cancer risk. Several important clinical questions deserve attention with respect to IBD therapy and cancer. First, does medical therapy for IBD predispose to developing cancer? Second, in an IBD patient with a history of cancer, does IBD therapy impact cancer recurrence? Third, once cancer develops in an IBD patient, is the cancer outcome different? Finally, in an IBD patient with current cancer, does the cancer therapy affect IBD outcomes? In a recent multicentric study, patients were identified based on a diagnosis of IBD and cancer with subsequent exposure to anti-tumor necrosis factor alpha (anti-TNFalpha arm), thiopurines or methotrexate (antimetabolite arm) or without subsequent IS exposure (control arm). Two hundred and fifty-five patients met the inclusion criteria. Prior cancers included 121 solid, 62 gastrointestinal, 55 dermatologic and 17 hematologic malignancies. During the follow-up period, 75 (29.4%) patients developed incident cancer: 36 (14.1%) a new cancer, 33 (12.9%) a recurrent cancer and 6 (2.4%) a new and recurrent cancer. Incident cancer rate per 100 person years for patients exposed to anti-TNFalpha, anti-metabolites and controls was 2.6 with 795 person-years of follow-up, 14.8 with 122 person-years of follow-up and 8.52 with 422 person-years of follow-up, respectively. In this series of IBD patients with a history of cancer, exposure to IS following a cancer diagnosis was not associated with an increased risk of incident cancer compared to patients who did not receive these agents. Prospective data are needed to confirm these findings. PMID- 26367258 TI - Sphingosine-1-Phosphate Receptor-1 Selective Agonist Enhances Collateral Growth and Protects against Subsequent Stroke. AB - BACKGROUND AND PURPOSE: Collateral growth after acute occlusion of an intracranial artery is triggered by increasing shear stress in preexisting collateral pathways. Recently, sphingosine-1-phosphate receptor-1 (S1PR1) on endothelial cells was reported to be essential in sensing fluid shear stress. Here, we evaluated the expression of S1PR1 in the hypoperfused mouse brain and investigated the effect of a selective S1PR1 agonist on leptomeningeal collateral growth and subsequent ischemic damage after focal ischemia. METHODS: In C57Bl/6 mice (n = 133) subjected to unilateral common carotid occlusion (CCAO) and sham surgery. The first series examined the time course of collateral growth, cell proliferation, and S1PR1 expression in the leptomeningeal arteries after CCAO. The second series examined the relationship between pharmacological regulation of S1PR1 and collateral growth of leptomeningeal anastomoses. Animals were randomly assigned to one of the following groups: LtCCAO and daily intraperitoneal (i.p.) injection for 7 days of an S1PR1 selective agonist (SEW2871, 5 mg/kg/day); sham surgery and daily i.p. injection for 7 days of SEW2871 after surgery; LtCCAO and daily i.p. injection for 7 days of SEW2871 and an S1PR1 inverse agonist (VPC23019, 0.5 mg/kg); LtCCAO and daily i.p. injection of DMSO for 7 days after surgery; and sham surgery and daily i.p. injection of DMSO for 7 days. Leptomeningeal anastomoses were visualized 14 days after LtCCAO by latex perfusion method, and a set of animals underwent subsequent permanent middle cerebral artery occlusion (pMCAO) 7 days after the treatment termination. Neurological functions 1 hour, 1, 4, and 7 days and infarction volume 7 days after pMCAO were evaluated. RESULTS: In parallel with the increase in S1PR1 mRNA levels, S1PR1 expression colocalized with endothelial cell markers in the leptomeningeal arteries, increased markedly on the side of the CCAO, and peaked 7 days after CCAO. Mitotic cell numbers in the leptomeningeal arteries increased after CCAO. Administration of the S1PR1 selective agonist significantly increased cerebral blood flow (CBF) and the diameter of leptomeningeal collateral vessels (42.9 +/- 2.6 MUm) compared with the controls (27.6 +/- 5.7 MUm; P < 0.01). S1PR1 inverse agonist administration diminished the effect of the S1PR1 agonist (P < 0.001). After pMCAO, S1PR1 agonist pretreated animals showed significantly smaller infarct volume (17.5% +/- 4.0% vs. 7.7% +/- 4.0%, P < 0.01) and better functional recovery than vehicle-treated controls. CONCLUSIONS: These results suggest that S1PR1 is one of the principal regulators of leptomeningeal collateral recruitment at the site of increased shear stress and provide evidence that an S1PR1 selective agonist has a role in promoting collateral growth and preventing of ischemic damage and neurological dysfunction after subsequent stroke in patients with intracranial major artery stenosis or occlusion. PMID- 26367259 TI - Correction: Correction: Genetic Evaluation of Dual-Purpose Buffaloes (Bubalus bubalis) in Colombia Using Principal Component Analysis. PMID- 26367260 TI - In Vitro and In Vivo Studies on Protective Action of N-Phenethyl Caffeamide against Photodamage of Skin. AB - In our previous study, N-phenethyl caffeamide (K36) was proved to act as an antioxidant and an antiphotoaging agent by inhibiting type I procollagen degradation and stimulating collagen synthesis in human skin fibroblasts. In the present study, in vitro and in vivo experiments were conducted to investigate the mechanism of action and the antiinflammatory and antiphotoaging activity of K36. K36 reduced UVB-induced cyclooxygenase-2 (COX-2) and inducible nitric oxide synthases (iNOS) expression by regulating IkappaB and p-IkappaB expression. K36 also inhibited the nuclear translocation of NF-kappaB. Furthermore, the inhibition of mitogen-activated protein (MAP) kinases by K36 was attributed to the downregulation of COX-2. Topically applying K36 led to efficient antiwrinkle formation and reduced UVB-induced erythema and thickness of epidermis in hairless mice. In addition, K36 penetrated into the skin of hairless mice. Our findings show that K36 has significant beneficial effects on antioxidant, antiinflammatory, and antiphotoaging activity and suggest that K36 can be developed as an antiaging agent for cosmetic and skin care products. PMID- 26367261 TI - [11C]MADAM Used as a Model for Understanding the Radiometabolism of Diphenyl Sulfide Radioligands for Positron Emission Tomography (PET). AB - In quantitative PET measurements, the analysis of radiometabolites in plasma is essential for determining the exact arterial input function. Diphenyl sulfide compounds are promising PET and SPECT radioligands for in vivo quantification of the serotonin transporter (SERT) and it is therefore important to investigate their radiometabolism. We have chosen to explore the radiometabolic profile of [11C]MADAM, one of these radioligands widely used for in vivo PET-SERT studies. The metabolism of [11C]MADAM/MADAM was investigated using rat and human liver microsomes (RLM and HLM) in combination with radio-HPLC or UHPLC/Q-ToF-MS for their identification. The effect of carrier on the radiometabolic rate of the radioligand [11C]MADAM in vitro and in vivo was examined by radio-HPLC. RLM and HLM incubations were carried out at two different carrier concentrations of 1 and 10 MUM. Urine samples after perfusion of [11C]MADAM/MADAM in rats were also analysed by radio-HPLC. Analysis by UHPLC/Q-ToF-MS identified the metabolites produced in vitro to be results of N-demethylation, S-oxidation and benzylic hydroxylation. The presence of carrier greatly affected the radiometabolism rate of [11C]MADAM in both RLM/HLM experiments and in vivo rat studies. The good concordance between the results predicted by RLM and HLM experiments and the in vivo data obtained in rat studies indicate that the kinetics of the radiometabolism of the radioligand [11C]MADAM is dose-dependent. This issue needs to be addressed when the diarylsulfide class of compounds are used in PET quantifications of SERT. PMID- 26367262 TI - Sphingosine-1-Phosphate Signaling Regulates Myogenic Responsiveness in Human Resistance Arteries. AB - We recently identified sphingosine-1-phosphate (S1P) signaling and the cystic fibrosis transmembrane conductance regulator (CFTR) as prominent regulators of myogenic responsiveness in rodent resistance arteries. However, since rodent models frequently exhibit limitations with respect to human applicability, translation is necessary to validate the relevance of this signaling network for clinical application. We therefore investigated the significance of these regulatory elements in human mesenteric and skeletal muscle resistance arteries. Mesenteric and skeletal muscle resistance arteries were isolated from patient tissue specimens collected during colonic or cardiac bypass surgery. Pressure myography assessments confirmed endothelial integrity, as well as stable phenylephrine and myogenic responses. Both human mesenteric and skeletal muscle resistance arteries (i) express critical S1P signaling elements, (ii) constrict in response to S1P and (iii) lose myogenic responsiveness following S1P receptor antagonism (JTE013). However, while human mesenteric arteries express CFTR, human skeletal muscle resistance arteries do not express detectable levels of CFTR protein. Consequently, modulating CFTR activity enhances myogenic responsiveness only in human mesenteric resistance arteries. We conclude that human mesenteric and skeletal muscle resistance arteries are a reliable and consistent model for translational studies. We demonstrate that the core elements of an S1P-dependent signaling network translate to human mesenteric resistance arteries. Clear species and vascular bed variations are evident, reinforcing the critical need for further translational study. PMID- 26367263 TI - Specific rhizobacterial resources: characterization and comparative analysis from contrasting coastal environments of Korea. AB - This study analyzed the rhizobacterial distribution from two coasts, which show contrasting climates and geographical and geological characteristics, to secure specific microbial resources. Furthermore, rhizobacteria were characterized and the results were comparatively analyzed with reference to the characteristics of two coastal environments. For this purpose, three representative halophyte species communities native to the Dokdo Islands and the East Sea coast of Korea were selected. Partial identification of rhizobacteria showed a clear difference between each sampling site and halophyte. Furthermore, isolates were characterized by their growth properties under NaCl or pH gradients related with previous geographical, geological, and climatic studies of the Dokdo Islands and the East Sea coast. A high proportion of the East Sea isolates showed halotolerance, but a high proportion of Dokdo isolates shared halophilic traits. Meanwhile, a higher proportion of East Sea isolates grew at a wider range of pH values than those of the Dokdo Islands. The results of our study suggest that unique rhizobacterial resources developed under specific rhizospheric conditions derived from halophytes interacting with their specific environment, even within the same coastal halophytic species. Therefore, this study proposes the necessity of securing characterized and unique microbial resources to apply to specific environments for the purpose of recovering and restoring sand dunes or salt damaged agricultural lands. PMID- 26367264 TI - Laboratory Evaluation of the Shinyei PPD42NS Low-Cost Particulate Matter Sensor. AB - OBJECTIVE: Finely resolved PM2.5 exposure measurements at the level of individual participants or over a targeted geographic area can be challenging due to the cost, size and weight of the monitoring equipment. We propose re-purposing the low-cost, portable and lightweight Shinyei PPD42NS particle counter as a particle counting device. Previous field deployment of this sensor suggests that it captures trends in ambient PM2.5 concentrations, but important characteristics of the sensor response have yet to be determined. Laboratory testing was undertaken in order to characterize performance. METHODS: The Shinyei sensors, in-line with a TSI Aerosol Particle Sizer (APS) model 3321, tracked particle decay within an aerosol exposure chamber. Test atmospheres were composed of monodisperse polystyrene spheres with diameters of 0.75, 1, 2 3 and 6 um as well as a polydisperse atmosphere of ASHRAE test dust #1. RESULTS: Two-minute block averages of the sensor response provide a measurement with low random error, within sensor, for particles in the 0.75-6MUm range with a limit of detection of 1 MUg/m3. The response slope of the sensors is idiomatic, and each sensor requires a unique response curve. A linear model captures the sensor response for concentrations below 50 MUg/m3 and for concentrations above 50 MUg/m3 a non linear function captures the response and saturates at 800 MUg/m3. The Limit of Detection (LOD) is 1 MUg/m3. The response time is on the order of minutes, making it appropriate for tracking short-term changes in concentration. CONCLUSIONS: When paired with prior evaluation, these sensors are appropriate for use as ambient particle counters for low and medium concentrations of respirable particles (< 100 ug/m3). Multiple sensors deployed over a spatial grid would provide valuable spatio-temporal variability in PM2.5 and could be used to validate exposure models. When paired with GPS tracking, these devices have the potential to provide time and space resolved exposure measurements for a large number of participants, thus increasing the power of a study. PMID- 26367265 TI - Sex Partnership and Self-Efficacy Influence Depression in Chinese Transgender Women: A Cross-Sectional Study. AB - BACKGROUND: Transgender women often suffer from transition-related discrimination and loss of social support due to their gender transition, which may pose considerable psychological challenges and may lead to a high prevalence of depression in this population. Increased self-efficacy may combat the adverse effects of gender transition on depression. However, few available studies have investigated the protective effect of self-efficacy on depression among transgender women, and there is a scarcity of research describing the mental health of Chinese transgender women. This study aims to describe the prevalence of depression among Chinese transgender women and to explore the associated factors. METHODS: A cross-sectional study was conducted in Shenyang, Liaoning Province of China by convenience sampling from January 2014 to July 2014. Two hundred and nine Chinese transgender women were interviewed face-to-face with questionnaires that covered topics including the Zung Self-Rating Depression Scale (SDS), demographic characteristics, transition status, sex partnership, perceived transgender-related discrimination, the Multidimensional Scale of Perceived Social Support (MSPSS) and the adapted General Self-efficacy Scale (GSES). A hierarchical multiple regression analysis was performed to explore the factors associated with SDS scores. RESULTS: The prevalence of depression among transgender women was 45.35%. Transgender women with regular partners or casual partners exhibited higher SDS scores than those without regular partners or casual partners. Regression analyses showed that sex partnership explained most (16.6%) of the total variance in depression scores. Self-efficacy was negatively associated with depression. CONCLUSIONS: Chinese transgender women experienced high levels of depression. Depression was best predicted by whether transgender women had a regular partner or a casual partner rather than transgender-related discrimination and transition status. Moreover, self-efficacy had positive effects on attenuating depression due to gender transition. Therefore, interventions should focus on improving the sense of self-efficacy among these women to enable them to cope with depression and to determine risky sex partnership characteristics, especially for regular and casual partners. PMID- 26367266 TI - Predominant polarity in bipolar disorders: refining or redefining diagnosis? PMID- 26367267 TI - Pycnogenol Attenuates the Release of Proinflammatory Cytokines and Expression of Perilipin 2 in Lipopolysaccharide-Stimulated Microglia in Part via Inhibition of NF-kappaB and AP-1 Activation. AB - Over activation of microglia results in the production of proinflammatory agents that have been implicated in various brain diseases. Pycnogenol is a patented extract from French maritime pine bark (Pinus pinaster Aiton) with strong antioxidant and anti-inflammatory potency. The present study investigated whether pycnogenol may be associated with the production of proinflammatory mediators in lipopolysaccharide-stimulated BV2 (mouse-derived) microglia. It was found that pycnogenol treatment was dose-dependently associated with significantly less release of nitricoxide (NO), TNF-alpha, IL-6 and IL-1beta, and lower levels of intercellular adhesion molecule1 (ICAM-1) and perilipin 2 (PLIN2). Furthermore, this effect was replicated in primary brain microglia. Levels of inducible NO synthase mRNA and protein were attenuated, whereas there was no change in the production of the anti-inflammatory cytokine IL-10. Further evidence indicated that pycnogenol treatment led to the suppression of NF-kappaB activation through inhibition of p65 translocation into the nucleus and inhibited DNA binding of AP 1, suggesting that these proinflammatory factors are associated with NF-kappaB and AP-1. We conclude that pycnogenol exerts anti-inflammatory effects through inhibition of the NF-kappaB and AP-1pathway, and may be useful as a therapeutic agent in the prevention of diseases caused by over activation of microglia. PMID- 26367268 TI - Recent insights into cell death and autophagy. AB - Macroautophagy (hereafter autophagy) is an evolutionarily-ancient mechanism by which cellular material is delivered to lysosomes for degradation. Autophagy and cell death are intimately linked. For example, both processes often use the same molecular machinery and recent work suggests that autophagy has great influence over a cell's decision to live or die. However, this decision-making is complicated by the fact that the role of autophagy in determining whether a cell should live or die goes both ways: autophagy inhibition can result in more or less cell death depending on the death stimulus, cell type or context. Autophagy may also differentially affect different types of cell death. In the present review, we discuss the recent literature that helps make sense of this apparently inconsistent role of autophagy in influencing a cell to live or die. PMID- 26367269 TI - Sexing Adult Pale-Winged Starlings Using Morphometric and Discriminant Function Analysis. AB - Accurate sexing of birds is vital for behavioral studies but can be a real problem in the field, especially for monomorphic species. Our goal here was to characterize the morphology of male and female monomorphic pale-winged starlings (Onychognathus nabouroup), a South African sturnid whose plumage is sexually monomorphic. Morphological measurements of genetically sexed animals indicated that males were statistically larger than females for five measurements: Mass, tail length, tarsus length and wing length. By using a Discriminant Function Analysis based on the measurements taken by one ringer, we were able to predict correctly the sex of 81.10% of the birds of data collected in the field and 77.9% of museum skins independently of year of capture and ringer. The model developed here should be useful for further field studies of this species. PMID- 26367272 TI - Synthesis, Structure, and Reactivity of a Tetranuclear Cerium(IV) Oxo Cluster Supported by the Klaui Tripodal Ligand [Co(eta(5) -C5 H5 ){P(O)(OEt)2 }3 ](.). AB - A tetranuclear Ce(IV) oxo cluster compound containing the Klaui tripodal ligand [Co(eta(5) -C5 H5 ){P(O)(OEt)2 }3 ](-) (LOEt (-) ) has been synthesized and its reactions with H2 O2 , CO2 , NO, and Bronsted acids have been studied. The treatment of [Ce(LOEt )(NO3 )3 ] with Et4 NOH in acetonitrile afforded the tetranuclear Ce(IV) oxo cluster [Ce4 (LOEt )4 O7 H2 ] (1) containing an adamantane-like {Ce4 (MU2 -O)6 } core with a MU4 -oxo ligand at the center. The reaction of 1 with H2 O2 resulted in the formation of the peroxo cluster [Ce4 (LOEt )4 (MU4 -O)(MU2 -O2 )4 (MU2 -OH)2 ] (2). The treatment of 1 with CO2 and NO led to isolation of [Ce(LOEt )2 (CO3 )] and [Ce(LOEt )(NO3 )3 ], respectively. The protonation of 1 with HCl, ROH (R=2,4,6-trichlorophenyl), and Ph3 SiOH yielded [Ce(LOEt )Cl3 ] (3), [Ce(LOEt )(OR)3 ] (4), and [Ce(LOEt )(OSiPh3 )3 ] (5), respectively. The chloride ligands in 3 are labile and can be abstracted by silver(I) salts. The treatment of 3 with AgOTs (OTs(-) =tosylate) and Ag2 O afforded [Ce(LOEt )(OTs)3 ] (6) and 1, respectively. The electrochemistry of the Ce-LOEt complexes has been studied by using cyclic voltammetry. The crystal structures of complexes 1-5 have been determined. PMID- 26367270 TI - The Potential for Mindfulness-Based Intervention in Workplace Mental Health Promotion: Results of a Randomized Controlled Trial. AB - OBJECTIVES: This study aims to intensively evaluate the effectiveness of mindfulness-based intervention (MBI) on mental illness risks (including psychological distress, prolonged fatigue, and perceived stress) and job strain (job control and job demands) for employees with poor mental health. METHODS: A longitudinal research design was adopted. In total, 144 participants were randomized to the intervention group or the control group. The intervention group participated in MBI for eight weeks. Measurements were collected for both groups at five time points: at pre-intervention (T1), at mid-intervention (T2), at the completion of intervention (T3), four weeks after intervention (T4), and eight weeks after intervention (T5). Data were analyzed according to the intention-to treat principle. A linear mixed model with two levels was employed to analyze the repeated measurement data. RESULTS: Compared with the control group, the intercepts (means at T3) for the intervention group were significantly lower on psychological distress, prolonged fatigue, and perceived stress when MBI was completed. Even with the demographic variables controlled, the positive effects remained. For growth rates of prolonged fatigue and perceived stress, participants in the intervention group showed a steeper decrease than did the participants in the control group. Regarding job strain, although the intercept (mean at T3) of job demands showed a significant decline when BMI was completed, the significance disappeared when the demographic variables were controlled. Moreover, the other results for job control and job demands did not show promising findings. CONCLUSION: As a workplace health promotion program, the MBI seems to have potential in improving mental illness risks for employees with poor mental health. However, there was insufficient evidence to support its effect on mitigating job strain. Further research on maintaining the positive effects on mental health for the long term and on developing innovative MBI to suit job strain are recommended. TRIAL REGISTRATION: ClinicalTrials.gov NCT02241070. PMID- 26367271 TI - New Fungus-Insect Symbiosis: Culturing, Molecular, and Histological Methods Determine Saprophytic Polyporales Mutualists of Ambrosiodmus Ambrosia Beetles. AB - Ambrosia symbiosis is an obligate, farming-like mutualism between wood-boring beetles and fungi. It evolved at least 11 times and includes many notorious invasive pests. All ambrosia beetles studied to date cultivate ascomycotan fungi: early colonizers of recently killed trees with poor wood digestion. Beetles in the widespread genus Ambrosiodmus, however, colonize decayed wood. We characterized the mycosymbionts of three Ambrosiodmus species using quantitative culturing, high-throughput metabarcoding, and histology. We determined the fungi to be within the Polyporales, closely related to Flavodon flavus. Culture independent sequencing of Ambrosiodmus minor mycangia revealed a single operational taxonomic unit identical to the sequences from the cultured Flavodon. Histological sectioning confirmed that Ambrosiodmus possessed preoral mycangia containing dimitic hyphae similar to cultured F. cf. flavus. The Ambrosiodmus Flavodon symbiosis is unique in several aspects: it is the first reported association between an ambrosia beetle and a basidiomycotan fungus; the mycosymbiont grows as hyphae in the mycangia, not as budding pseudo-mycelium; and the mycosymbiont is a white-rot saprophyte rather than an early colonizer: a previously undocumented wood borer niche. Few fungi are capable of turning rotten wood into complete animal nutrition. Several thousand beetle-fungus symbioses remain unstudied and promise unknown and unexpected mycological diversity and enzymatic innovations. PMID- 26367273 TI - NO-Donor Dihydroartemisinin Derivatives as Multitarget Agents for the Treatment of Cerebral Malaria. AB - Hybrid products in which the dihydroartemisinin scaffold is combined with NO donor furoxan and NONOate moieties have been synthesized and studied as potential tools for the treatment of cerebral malaria (CM). The designed products were able to dilate rat aorta strips precontracted with phenylephrine with a NO-dependent mechanism. All hybrid compounds showed preserved antiplasmodial activity in vitro and in vivo against Plasmodium berghei ANKA, comparable to artesunate and artemether. Hybrid 10, selected for additional studies, was capable of increasing survival of mice with late-stage CM from 27.5% to 51.6% compared with artemether. Artemisinin-NO-donor hybrid compounds show promise as potential new drugs for treating cerebral malaria. PMID- 26367275 TI - Nonstoichiometric Oxides as Low-Cost and Highly-Efficient Oxygen Reduction/Evolution Catalysts for Low-Temperature Electrochemical Devices. PMID- 26367274 TI - Mycobacterium tuberculosis Upregulates TNF-alpha Expression via TLR2/ERK Signaling and Induces MMP-1 and MMP-9 Production in Human Pleural Mesothelial Cells. AB - BACKGROUND: Tumor necrosis factor (TNF)-alpha and matrix metalloproteinases (MMPs) are elevated in pleural fluids of tuberculous pleuritis (TBP) where pleural mesothelial cells (PMCs) conduct the first-line defense against Mycobacterium tuberculosis (MTB). However, the clinical implication of TNF-alpha and MMPs in TBP and the response of PMCs to MTB infection remain unclear. METHODS: We measured pleural fluid levels of TNF-alpha and MMPs in patients with TBP (n = 18) or heart failure (n = 18) as controls. Radiological scores for initial effusion amount and residual pleural fibrosis at 6-month follow-up were assessed. In vitro human PMC experiments were performed to assess the effect of heat-killed M. tuberculosis H37Ra (MTBRa) on the expression of TNF-alpha and MMPs. RESULTS: As compared with controls, the effusion levels of TNF-alpha, MMP-1 and MMP-9 were significantly higher and correlated positively with initial effusion amount in patients with TBP, while TNF-alpha and MMP-1, but not MMP-9, were positively associated with residual pleural fibrosis of TBP. Moreover, effusion levels of TNF-alpha had positive correlation with those of MMP-1 and MMP 9 in TBP. In cultured PMCs, MTBRa enhanced TLR2 and TLR4 expression, activated ERK signaling, and upregulated TNF-alpha mRNA and protein expression. Furthermore, knockdown of TLR2, but not TLR4, significantly inhibited ERK phosphorylation and TNF-alpha expression. Additionally, both MTBRa and TNF-alpha markedly induced MMP-1 and MMP-9 synthesis in human PMCs, and TNF-alpha neutralization substantially reduced the production of MMP-1, but not MMP-9, in response to MTBRa stimulation. CONCLUSION: MTBRa activates TLR2/ERK signalings to induce TNF-alpha and elicit MMP-1 and MMP-9 in human PMCs, which are associated with effusion volume and pleural fibrosis and may contribute to pathogenesis of TBP. Further investigation of manipulation of TNF-alpha and MMP expression in pleural mesothelium may provide new insights into the mechanisms and rational treatment strategies for TBP. PMID- 26367276 TI - Intrinsic MyD88-Akt1-mTOR Signaling Coordinates Disparate Tc17 and Tc1 Responses during Vaccine Immunity against Fungal Pneumonia. AB - Fungal infections have skyrocketed in immune-compromised patients lacking CD4+ T cells, underscoring the need for vaccine prevention. An understanding of the elements that promote vaccine immunity in this setting is essential. We previously demonstrated that vaccine-induced IL-17A+ CD8+ T cells (Tc17) are required for resistance against lethal fungal pneumonia in CD4+ T cell-deficient hosts, whereas the individual type I cytokines IFN-gamma, TNF-alpha and GM-CSF, are dispensable. Here, we report that T cell-intrinsic MyD88 signals are crucial for these Tc17 cell responses and vaccine immunity against lethal fungal pneumonia in mice. In contrast, IFN-gamma+ CD8+ cell (Tc1) responses are largely normal in the absence of intrinsic MyD88 signaling in CD8+ T cells. The poor accumulation of MyD88-deficient Tc17 cells was not linked to an early onset of contraction, nor to accelerated cell death or diminished expression of anti apoptotic molecules Bcl-2 or Bcl-xL. Instead, intrinsic MyD88 was required to sustain the proliferation of Tc17 cells through the activation of mTOR via Akt1. Moreover, intrinsic IL-1R and TLR2, but not IL-18R, were required for MyD88 dependent Tc17 responses. Our data identify unappreciated targets for augmenting adaptive immunity against fungi. Our findings have implications for designing fungal vaccines and immune-based therapies in immune-compromised patients. PMID- 26367278 TI - Response of the endangered tropical dry forests to climate change and the role of Mexican Protected Areas for their conservation. AB - Assuming that co-distributed species are exposed to similar environmental conditions, ecological niche models (ENMs) of bird and plant species inhabiting tropical dry forests (TDFs) in Mexico were developed to evaluate future projections of their distribution for the years 2050 and 2070. We used ENM-based predictions and climatic data for two Global Climate Models, considering two Representative Concentration Pathway scenarios (RCP4.5/RCP8.5). We also evaluated the effects of habitat loss and the importance of the Mexican system of protected areas (PAs) on the projected models for a more detailed prediction of TDFs and to identify hot spots that require conservation actions. We identified four major distributional areas: the main one located along the Pacific Coast (from Sonora to Chiapas, including the Cape and Bajio regions, and the Balsas river basin), and three isolated areas: the Yucatan peninsula, central Veracruz, and southern Tamaulipas. When considering the effect of habitat loss, a significant reduction (~61%) of the TDFs predicted area occurred, whereas climate-change models suggested (in comparison with the present distribution model) an increase in area of 3.0-10.0% and 3.0-9.0% for 2050 and 2070, respectively. In future scenarios, TDFs will occupy areas above its current average elevational distribution that are outside of its present geographical range. Our findings show that TDFs may persist in Mexican territory until the middle of the XXI century; however, the challenges about long-term conservation are partially addressed (only 7% unaffected within the Mexican network of PAs) with the current Mexican PAs network. Based on our ENM approach, we suggest that a combination of models of species inhabiting present TDFs and taking into account change scenarios represent an invaluable tool to create new PAs and ecological corridors, as a response to the increasing levels of habitat destruction and the effects of climate change on this ecosystem. PMID- 26367279 TI - Pharmacological Characterization of ZYAN1, a Novel Prolyl Hydroxylase Inhibitor for the Treatment of Anemia. AB - Prolyl hydroxylase (PHD) inhibitors stabilize hypoxia inducible factor (HIF), and exert antianemic effect by potentiating erythropoietin (EPO) expression and down regulation of hepcidin. ZYAN1 is a novel PHD inhibitor under clinical development for the treatment of anemia. The pharmacodynamic effects of acute and chronic dosing of ZYAN1 were assessed in normal and 5/6 nephrectomized Wistar rats. The effect of ZYAN1 was also investigated in cisplatin-induced anemia using C57 mice. Acute treatment with ZYAN1 increased circulating EPO levels (10.3 +/- 3.7 and 40.0 +/- 8.5 fold rise at 15 and 30 mg/kg, respectively), reticulocyte count (4.2 +/- 0.5 and 6.0 +/- 0.2 fold rise at 15 and 30 mg/kg, respectively) and stabilized HIF (28% increase at 45 mg/kg) in normal rats. Nephrectomized rats showed similar dose-related pharmacodynamic effects. In a 28-day study in nephrectomized rats, ZYAN1 administered every alternate day, caused increase in hemoglobin (1.9 +/- 0.3 and 2.5 +/- 0.4 g/dL) and RBC count (10.7 +/- 4.0 and 14.0 +/- 4.1%) at 15 and 30 mg/kg respectively. In cisplatin-treated mice also an increase in hemoglobin (3.4 +/- 0.2 and 5.9 +/- 0.2 g/dL) and RBC count (22.5 +/- 2.2 and 37.3 +/- 1.7%) at 15 and 30 mg/kg respectively was observed. ZYAN1's effects on hemoglobin and RBC count were distinct from darbepoietin. ZYAN1 demonstrated hematinic potential by combined effects on EPO release and efficient iron utilization. The efficacy of ZYAN1 in disease models of different etiologies suggests that it will be useful in treating wide spectrum of anemia patients. PMID- 26367277 TI - Lipocalin (LCN) 2 Mediates Pro-Atherosclerotic Processes and Is Elevated in Patients with Coronary Artery Disease. AB - BACKGROUND: Lipocalin (LCN) 2 is associated with multiple acute and chronic inflammatory diseases but the underlying molecular and cellular mechanisms remain unclear. Here, we investigated whether LCN2 is released from macrophages and contributes to pro-atherosclerotic processes and whether LCN2 plasma levels are associated with the severity of coronary artery disease progression in humans. METHODS AND RESULTS: In an autocrine-paracrine loop, tumor necrosis factor (TNF) alpha promoted the release of LCN2 from murine bone-marrow derived macrophages (BMDM) and vice versa. Moreover, LCN2 stimulation of BMDM led to up-regulation of M1 macrophage markers. In addition, enhanced migration of monocytic J774A.1 cells towards LCN2 was observed. Furthermore, LCN2 increased the expression of the scavenger receptors Lectin-like oxidized low-density lipoprotein receptor-1 (LOX 1) as well as scavenger receptor class A-1 (SRA-1) and induced the conversion of macrophages to foam cells. In atherosclerotic lesions of low density lipoprotein receptor-deficient (ldlr-/-) mice fed a high fat, high cholesterol diet, LCN2 was found to be co-localized with macrophages in the shoulder region of the atherosclerotic plaque. In addition, LCN2 plasma levels were significantly increased in plasma samples of these mice. Finally, LCN2 plasma levels correlated with the severity of coronary artery disease (CAD) in patients as determined by coronary angiography. CONCLUSIONS: Here we demonstrated that LCN2 plays a pivotal role in processes involved in atherogenesis by promoting polarization and migration of monocytic cells and development of macrophages towards foam cells. Moreover, LCN2 may be used as a prognostic marker to determine the status of CAD progression. PMID- 26367280 TI - In Vivo Long-Term Monitoring of Circulating Tumor Cells Fluctuation during Medical Interventions. AB - The goal of this research was to study the long-term impact of medical interventions on circulating tumor cell (CTC) dynamics. We have explored whether tumor compression, punch biopsy or tumor resection cause dissemination of CTCs into peripheral blood circulation using in vivo fluorescent flow cytometry and breast cancer-bearing mouse model inoculated with MDA-MB-231-Luc2-GFP cells in the mammary gland. Two weeks after tumor inoculation, three groups of mice were the subject of the following interventions: (1) tumor compression for 15 minutes using 400 g weight to approximate the pressure during mammography; (2) punch biopsy; or (3) surgery. The CTC dynamics were determined before, during and six weeks after these interventions. An additional group of tumor-bearing mice was used as control and did not receive an intervention. The CTC dynamics in all mice were monitored weekly for eight weeks after tumor inoculation. We determined that tumor compression did not significantly affect CTC dynamics, either during the procedure itself (P = 0.28), or during the 6-week follow-up. In the punch biopsy group, we observed a significant increase in CTC immediately after the biopsy (P = 0.02), and the rate stayed elevated up to six weeks after the procedure in comparison to the tumor control group. The CTCs in the group of mice that received a tumor resection disappeared immediately after the surgery (P = 0.03). However, CTC recurrence in small numbers was detected during six weeks after the surgery. In the future, to prevent these side effects of medical interventions, the defined dynamics of intervention-induced CTCs may be used as a basis for initiation of aggressive anti-CTC therapy at time-points of increasing CTC number. PMID- 26367281 TI - A Randomized, Double-Blind, Placebo-Controlled Trial of Adjunctive Metformin Therapy in Overweight/Obese Youth with Type 1 Diabetes. AB - CONTEXT: Insulin resistance has been proposed as one of the causes of poor glycemic control in overweight/obese youth with type 1 diabetes (T1D). However, the role of adjunctive metformin, an insulin sensitizer, on glycemic control in these patients is unclear. OBJECTIVE: To compare the effect of metformin vs. placebo on hemoglobin A1c (HbA1c), total daily dose (TDD) of insulin, and other parameters in overweight/obese youth with T1D. HYPOTHESIS: Adjunctive metformin therapy will improve glycemic control in overweight/obese youth with T1D. DESIGN, SETTING, AND PARTICIPANTS: A 9-mo randomized, double-blind, placebo controlled trial of metformin and placebo in 28 subjects (13m/15f) of ages 10-20years (y), with HbA1c >8% (64 mmol/mol), BMI >85%, and T1D > 12 months was conducted at a university outpatient facility. The metformin group consisted of 15 subjects (8 m/ 7f), of age 15.0 +/- 2.5 y; while the control group was made up of 13 subjects (5m/ 8f), of age 14.5 +/- 3.1y. All participants employed a self-directed treat to-target insulin regimen based on a titration algorithm of (-2)-0-(+2) units to adjust their long-acting insulin dose every 3rd day from -3 mo through +9 mo to maintain fasting plasma glucose (FPG) between 90-120 mg/dL (5.0-6.7 mmol/L). Pubertal maturation was determined by Tanner stage. RESULTS: Over the course of the 9 months of observation, the between-treatment differences in HbA1c of 0.4% (9.85% [8.82 to 10.88] for placebo versus 9.46% [8.47 to 10.46] for metformin) was not significant (p = 0.903). There were non-significant reduction in fasting plasma glucose (189.4 mg/dL [133.2 to 245.6] for placebo versus 170.5 mg/dL [114.3 to 226.7] for metformin), (p = 0.927); total daily dose (TDD) of short acting insulin per kg body weight/day(p = 0.936); and the TDD of long-acting insulin per kg body weight per day (1.15 units/kg/day [0.89 to 1.41] for placebo versus 0.90 units/kg/day [0.64 to 1.16] for metformin) (p = 0.221). There was no difference in the occurrence of hypoglycemia between the groups. CONCLUSIONS: This 9-month RCT of adjunctive metformin therapy in overweight and obese youth with T1D resulted in a 0.4% lower HbA1c value in the metformin group compared to the placebo group. TRIAL REGISTRATION: ClinicalTrial.gov NCT01334125. PMID- 26367283 TI - Correction: Genome-Wide Analyses Suggest Mechanisms Involving Early B-Cell Development in Canine IgA Deficiency. PMID- 26367282 TI - Mitochondrial Genome Analyses Suggest Multiple Trichuris Species in Humans, Baboons, and Pigs from Different Geographical Regions. AB - BACKGROUND: The whipworms Trichuris trichiura and Trichuris suis are two parasitic nematodes of humans and pigs, respectively. Although whipworms in human and non-human primates historically have been referred to as T. trichiura, recent reports suggest that several Trichuris spp. are found in primates. METHODS AND FINDINGS: We sequenced and annotated complete mitochondrial genomes of Trichuris recovered from a human in Uganda, an olive baboon in the US, a hamadryas baboon in Denmark, and two pigs from Denmark and Uganda. Comparative analyses using other published mitochondrial genomes of Trichuris recovered from a human and a porcine host in China and from a francois' leaf-monkey (China) were performed, including phylogenetic analyses and pairwise genetic and amino acid distances. Genetic and protein distances between human Trichuris in Uganda and China were high (~19% and 15%, respectively) suggesting that they represented different species. Trichuris from the olive baboon in US was genetically related to human Trichuris in China, while the other from the hamadryas baboon in Denmark was nearly identical to human Trichuris from Uganda. Baboon-derived Trichuris was genetically distinct from Trichuris from francois' leaf monkey, suggesting multiple whipworm species circulating among non-human primates. The genetic and protein distances between pig Trichuris from Denmark and other regions were roughly 9% and 6%, respectively, while Chinese and Ugandan whipworms were more closely related. CONCLUSION AND SIGNIFICANCE: Our results indicate that Trichuris species infecting humans and pigs are phylogenetically distinct across geographical regions, which might have important implications for the implementation of suitable and effective control strategies in different regions. Moreover, we provide support for the hypothesis that Trichuris infecting primates represents a complex of cryptic species with some species being able to infect both humans and non-human primates. PMID- 26367284 TI - Vectorial ray-based diffraction integral. AB - Laser interferometry, as applied in cutting-edge length and displacement metrology, requires detailed analysis of systematic effects due to diffraction, which may affect the measurement uncertainty. When the measurements aim at subnanometer accuracy levels, it is possible that the description of interferometer operation by paraxial and scalar approximations is not sufficient. Therefore, in this paper, we place emphasis on models based on nonparaxial vector beams. We address this challenge by proposing a method that uses the Huygens integral to propagate the electromagnetic fields and ray tracing to achieve numerical computability. Toy models are used to test the method's accuracy. Finally, we recalculate the diffraction correction for an interferometer, which was recently investigated by paraxial methods. PMID- 26367285 TI - Cramer-Rao lower bound calculations for image registration using simulated phenomenology. AB - The Cramer-Rao lower bound (CRLB) is a valuable tool to quantify fundamental limits to estimation problems associated with imaging systems, and has been used previously to study image registration performance bounds. Most existing work, however, assumes constant-variance noise; for many applications, noise is signal dependent. Further, linear filters applied after detection can potentially yield reduced registration error, but prior work has not treated the CRLB behavior caused by filter-imposed noise correlation. We have developed computational methods to efficiently generalize existing image registration CRLB calculations to account for the effect of both signal-dependent noise and linear filtering on the estimation of rigid-translation ("shift") parameters. Because effective use of the CRLB requires radiometrically realistic simulated imagery, we have also developed methods to exploit computer animation software and available optical properties databases to conveniently build and modify synthetic objects for radiometric image simulations using DIRSIG. In this paper, we present the generalized expressions for the rigid shift Fisher information matrix and discuss the properties of the associated CRLB. We discuss the methods used to synthesize object "sets" for use in DIRSIG, and then demonstrate the use of simulated imagery in the CRLB code to choose an error-minimizing filter and optimal integration time for an image-based tracker in the presence of random platform jitter. PMID- 26367286 TI - Precision of polarization-resolved second harmonic generation microscopy limited by photon noise for samples with cylindrical symmetry. AB - The estimation of parameters in polarization-resolved two-photon microscopy response perturbed by photon noise is analyzed in the context of second harmonic generation for the distribution of molecules presenting cylindrical symmetry. The estimation task is investigated using the Cramer-Rao lower bound for Poisson photon noise. It is shown that a noniterative technique can lead to estimation results that have good efficiencies for most of the physical possible values of the sample parameters for sufficiently high photon levels. The trade-off, between the number of incident polarization states and the total number of measured photons, that can be obtained with the Cramer-Rao lower bound is also discussed. PMID- 26367288 TI - Design of guided-mode resonance mirrors for short laser cavities. AB - A guided-mode resonance mirror (GMRM) consists of a waveguide grating integrated on an optical buffer layer on a high-reflection substrate. An incident free-space wave at the resonance wavelength is once coupled by the grating to a guided mode and coupled again by the same grating back to free space. The reflection characteristics of a GMRM are numerically calculated and theoretically analyzed. It is predicted that notch filtering or flat reflection spectra are obtained depending on the optical buffer layer thickness. Design of short cavities using a GMRM is discussed for potential application in surface-mount packaging of diode lasers onto a photonic circuit board. PMID- 26367287 TI - Quantitative assessment of the impact of blood pulsation on images of the pupil in infrared light. AB - Pulsation in the blood vessels of the eye has a big impact on the dynamics of the entire eyeball and its individual elements. Blood pulsation in the retina can be recorded by the pupil, whose size is also subject to dynamic changes. The study involved synchronous measurements of pupil size using a high-speed camera, and blood pulsation using a pulse oximeter placed on the ear lobe. In addition, there were no metrologically significant differences in the phase shift between the average brightness of the individual pupil quadrants. Blood pulsation in other ocular tissues can affect the dynamics of the optical properties of the eye. As demonstrated in this paper, it affects the pupil behavior and its parameters to a considerable extent. PMID- 26367289 TI - Empirical model for matching spectrophotometric reflectance of yarn windings and multispectral imaging reflectance of single strands of yarns. AB - The state-of-the-art multispectral imaging system can directly acquire the reflectance of a single strand of yarn that is impossible for traditional spectrophotometers. Instead, the spectrophotometric reflectance of a yarn winding, which is constituted by yarns wound on a background card, is regarded as the yarn reflectance in textile. While multispectral imaging systems and spectrophotometers can be separately used to acquire the reflectance of a single strand of yarn and corresponding yarn winding, the quantitative relationship between them is not yet known. In this paper, the relationship is established based on models that describe the spectral response of a spectrophotometer to a yarn winding and that of a multispectral imaging system to a single strand of yarn. The reflectance matching function from a single strand of yarn to corresponding yarn winding is derived to be a second degree polynomial function, which coefficients are the solutions of a constrained nonlinear optimization problem. Experiments on 100 pairs of samples show that the proposed approach can reduce the color difference between yarn windings and single strands of yarns from 2.449 to 1.082 CIEDE2000 units. The coefficients of the optimal reflection matching function imply that the reflectance of a yarn winding measured by a spectrophotometer consists of not only the intrinsic reflectance of yarn but also the nonignorable interreflection component between yarns. PMID- 26367290 TI - Exceptional polarization structures near the C-lines in diffracted near fields. AB - We study the polarization structures in the vicinity of C-lines in the near fields diffracted from a pair of small holes. We find that, when the incident light is circularly polarized, both the true C-lines and the structures near them are controlled only by the longitudinal component. Furthermore, we find that all the existing singular lines of circular polarization have the winding number +/ 1, which is very different than the usual numbers +/-1/2, and the structure of major axes of the polarization ellipses surrounding these lines are shown to form structures different than the Mobius strip type. All these features prove to be stable upon small changes of shapes or positions of the apertures. However, C lines with a unit winding number split into two C-lines of half-winding numbers when the incident light is elliptically polarized light. PMID- 26367291 TI - Conformal cubical 3D transformation-based metamaterial invisibility cloak: Erratum. AB - A correction to the definition of the constant a introduced after Eq. (4) in [J. Opt. Soc. Am. A30, 7-12 (2013)JOAOD60740-323210.1364/JOSAA.30.000007] is given. PMID- 26367292 TI - Diagrammatic and asymptotic approaches to the origins of radiative transport theory: tutorial. AB - The radiative transport equation (RTE) is used widely to describe the propagation of multiply scattered light in disordered media. In this tutorial, we present two derivations of the RTE for scalar wave fields. The first derivation is based on diagrammatic perturbation theory, while the second stems from an asymptotic multiscale expansion. Although the two approaches are quite distinct mathematically, some common ground can be found and is discussed. PMID- 26367293 TI - Electromagnetic inhomogeneous waves at planar boundaries: tutorial. AB - In this review paper, we summarize the fundamental properties of inhomogeneous waves at the planar interface between two media. We point out the main differences between the wave types: lateral waves, surface waves, and leaky waves. We analyze each kind of inhomogeneous wave, giving a quasi-optical description and explaining the physical origin of some of their properties. PMID- 26367294 TI - Analytical solution for Gamo entropy under spatially partial coherent illumination. AB - We present a methodology for obtaining the analytical solution of the Gamo entropy, defined by the intensity matrix proposed by Gamo [J. Opt. Soc. Am.47, 976 (1957)JOSAAH0030-394110.1364/JOSA.47.000976]. The matrix, which consists of numerous image amplitudes at all the sampling points of the entire imaging plane, is generally infinite-dimensional. The essence of our theory is that the computational difficulties arising because of the infinite-dimensionality are avoided by introducing the inner products of two image amplitudes. The integral in continuous space plays the role of a buffer against the infinite dimensionality. The validity of the approach is confirmed by comparing our analytical solution and Yamazoe's numerical simulations [J. Opt. Soc. Am. A28, 448 (2011)JOAOD60740-323210.1364/JOSAA.28.000448]. PMID- 26367295 TI - General lossless planar coupler design algorithms. AB - This paper reviews and extends two classes of algorithms for the design of planar couplers with any unitary transfer matrix as design goals. Such couplers find use in optical sensing for fading free interferometry, coherent optical network demodulation, and also for quantum state preparation in quantum optical experiments and technology. The two classes are (1) "atomic coupler algorithms" decomposing a unitary transfer matrix into a planar network of 2*2 couplers, and (2) "Lie theoretic algorithms" concatenating unit cell devices with variable phase delay sets that form canonical coordinates for neighborhoods in the Lie group U(N), so that the concatenations realize any transfer matrix in U(N). As well as review, this paper gives (1) a Lie theoretic proof existence proof showing that both classes of algorithms work and (2) direct proofs of the efficacy of the "atomic coupler" algorithms. The Lie theoretic proof strengthens former results. 5*5 couplers designed by both methods are compared by Monte Carlo analysis, which would seem to imply atomic rather than Lie theoretic methods yield designs more resilient to manufacturing imperfections. PMID- 26367296 TI - Point-by-point near-field optical energy deposition around plasmonic nanospheres in absorbing media. AB - Here we investigate the effects of absorbing media on plasmon-enhanced near-field optical energy deposition. We find that increasing absorption by the medium results in increased particle scattering at the expense of particle absorption, and that much of this increased particle scattering is absorbed by the medium close to the particle surface. We present an analytical method for evaluating the spatial distribution of near-field enhanced absorption surrounding plasmonic metal nanospheres in absorbing media using a new point-by-point method. We propose criteria to define relevant near-field boundaries and calculate the properties of the local absorption enhancement, which redistributes absorption to the near-field and decays asymptotically as a function of the distance from the particle to background levels. Using this method, we performed a large-scale parametric study to understand the effect of particle size and wavelength on the near-field absorption for gold nanoparticles in aqueous media and silicon, and identified conditions that are relevant to enhanced local infrared absorption in silicon. The presented approach provides insight into the local energy transfer around plasmonic nanoparticles for predicting near-field effects for advanced concepts in optical sensing, thin-film solar cells, nonlinear imaging, and photochemical applications. PMID- 26367297 TI - Random errors for the measurement of central positions in white-light interferometry with the least-squares method. AB - This paper analyzes the effect of random noise on the measurement of central positions of white-light correlograms with the least-squares method. Measurements of two types of central positions, the central position of the envelope (CPE) and the central position of the central fringe (CPCF), are investigated. Two types of random noise, intensity noise and position noise, are considered. Analytic expressions for random error due to intensity noise (REIN) and random error due to position noise (REPN) are derived. The theoretical results are compared with the random errors estimated from computer simulations. Random errors of CPE measurement are compared with those of CPCF measurement. Relationships are investigated between the random errors and the wavelength of the light source. The REPN of CPCF measurement has been found to be independent of the wavelength of the light source and the amplitude of the central fringe. PMID- 26367298 TI - Lycurgus Cup: inverse problem using photographs for characterization of matter. AB - Photographs of the Lycurgus Cup with a source light inside and outside exhibit purple and green colors, respectively (dichroism). A model relying on the scattering of light to colors in the photographs is proposed and used within an inverse problem algorithm, to deduce radius and composition of metallic particles, and the refractive index of the surrounding glass medium. The inverse problem algorithm is based on a hybridization of particle swarm optimization and of the simulated annealing methods. The results are compared to experimental measurements on a small sample of glass. The linear laws that are deduced from sets of possible parameters producing the same color in the photographs help simplify the understanding of phenomena. The proportion of silver to gold in nanoparticles is found to be in agreement, but a large proportion of copper is also found. The retrieved refractive index of the surrounding glass is close to 2. PMID- 26367299 TI - Focus correction in an apodized system with spherical aberration. AB - We performed a theoretical and computational analysis of the through-focus axial irradiance in a system with a Gaussian amplitude pupil function and fourth- and sixth-order spherical aberration (SA). Two cases are analyzed: low aberrated systems, and the human eye containing significant levels of SA and a natural apodization produced by the Stiles-Crawford effect. Results show that apodization only produces a refraction change of the plane that maximized the Strehl ratio for eyes containing significant levels of negative SA. PMID- 26367300 TI - Poynting theorem constraints on the signs of the imaginary parts of the electromagnetic constitutive parameters: comment. AB - Contrary to an unphysical conclusion obtained by Alavikia et al. [J. Opt. Soc. Am. A32, 522 (2015)JOAOD60740-323210.1364/JOSAA.32.000522], the imaginary parts of both the permittivity and the permeability of any linear, homogeneous, passive, spatially local, dielectric-magnetic material are always positive, independent of the signs of their real parts. PMID- 26367302 TI - Propagation characteristics of Bessel beams generated by continuous, incoherent light sources. AB - We investigate the propagation behavior of Bessel beams generated by incoherent, continuous light sources. We perform experiments with narrowband and broadband light emitting diodes, and, for comparison, with a laser diode. We observe that the formation of Bessel beams is affected minimally by temporal coherence, while spatial coherence determines the longitudinal evolution of the beam profile. With spatially incoherent beams, the fringe contrast is comparable to the coherent case at the beginning of the Bessel zone, while it completely fades away by propagation, turning into a cylindrical light pipe. Our results show that beam shaping methods can be extended to cases of limited spatial coherence, paving the way for potential new uses and applications of such sources. PMID- 26367303 TI - Effect of the focal shaping generated from different double-mode cylindrical vector beams. AB - We investigate three-dimensional focus shaping generated from double-mode cylindrical vector beams with the Gaussian and Bessel-Gaussian pupil apodization functions by choosing the suitable polarization states of beams. Further, we compare them with that generated from the Laguerre-Gaussian pupil apodization function in the same situation. We find that the focus shaping generated from the Gaussian beam has the smallest zero intensity spot size. However, the situation of the Bessel-Gaussian beam not only possesses stability, which makes it suitable when applied in optical trapping, but also shows the best uniformity, which indicates its excellent performance in super-resolution fluorescence microscopy. PMID- 26367304 TI - Numerical tool to take nonlocal effects into account in metallo-dielectric multilayers. AB - We provide a numerical tool to quantitatively study the impact of nonlocality arising from free electrons in metals on the optical properties of metallo dielectric multilayers. We found that scattering matrices are particularly well suited to take into account the electron response through the application of the hydrodynamic model. Though effects due to nonlocality are, in general, quite small, they, nevertheless, can be important for very thin (typically below 10 nm) metallic layers, as in those used in structures characterized by exotic dispersion curves. Such structures include those with a negative refractive index, hyperbolic metamaterials, and near-zero index materials. Higher wave vectors mean larger nonlocal effects, so that it is not surprising that subwavelength imaging capabilities of hyperbolic metamaterials are found to be sensitive to nonlocal effects. We find in all cases that the inclusion of nonlocal effects leads to at least a 5% higher transmission through the considered structure. PMID- 26367305 TI - Policy, procedures, and goals at JOSA A: editorial. AB - Editorial policy and procedures are described for the benefit of potential authors and reviewers. These policies are described in the context of our goals for the journal. PMID- 26367306 TI - Re-examining the effects of verbal instructional type on early stage motor learning. AB - The present study investigated the differential effects of analogy and explicit instructions on early stage motor learning and movement in a modified high jump task. Participants were randomly assigned to one of three experimental conditions: analogy, explicit light (reduced informational load), or traditional explicit (large informational load). During the two-day learning phase, participants learned a novel high jump technique based on the 'scissors' style using the instructions for their respective conditions. For the single-day testing phase, participants completed both a retention test and task-relevant pressure test, the latter of which featured a rising high-jump-bar pressure manipulation. Although analogy learners demonstrated slightly more efficient technique and reported fewer technical rules on average, the differences between the conditions were not statistically significant. There were, however, significant differences in joint variability with respect to instructional type, as variability was lowest for the analogy condition during both the learning and testing phases, and as a function of block, as joint variability decreased for all conditions during the learning phase. Findings suggest that reducing the informational volume of explicit instructions may mitigate the deleterious effects on performance previously associated with explicit learning in the literature. PMID- 26367308 TI - Pathological Examination of the Placenta in the United Kingdom: Is It Time for a Uniform Approach? PMID- 26367307 TI - Toll-like receptor 4 signaling: A common pathway for interactions between prooxidants and extracellular disulfide high mobility group box 1 (HMGB1) protein coupled activation. AB - Necrotic cells passively release HMGB1, which can stimulate TLR4 in an autocrine fashion to potentially initiate "sterile" inflammation that maintains different disease states. We have shown that prooxidants can induce NF-kappaB activation through TLR4 stimulation. We examined whether prooxidants enhance HMGB1-induced TLR4 signaling through NF-kappaB activation. We used LPS-EK as a specific agonist for TLR4, and PPC and SIN-1 as in situ sources for ROS. As model systems, we used HEK-Blue cells (stably transfected with mouse TLR4), RAW-BlueTM cells (derived from murine RAW 264.7 macrophages) and primary murine macrophages from TLR4-KO mice. Both HEK-Blue and RAW-Blue 264.7 cells express optimized secreted embryonic alkaline phosphatase (SEAP) reporter under the control of a promoter inducible by NF-kappaB. We treated cells with HMGB1 alone and/or in conjunction with prooxidants and/or inhibitors using SEAP release as a measure of TLR4 stimulation. HMGB1 alone and/or in conjunction with prooxidants increased TNFalpha and IL-6 released from TLR4-WT, but not from TLR4-KO macrophages. Pro oxidants increased HMGB1 release, which we quantified by ELISA. We used both fluorescence microscopy imaging and flow cytometry to quantify the expression of intracellular ROS. TLR4-neutralizing antibody decreased prooxidant-induced HMGB1 release. Prooxidants promoted HMGB1-induced NF-kappaB activation as determined by increased release of SEAP and TNF-alpha, and accumulation of iROS. HMGB1 (Box A), anti-HMGB1 and anti-TLR4-neutralizing pAbs inhibited HMGB1-induced NF-kappaB activation, but HMGB1 (Box A) and anti-HMGB1 pAb had no effect on prooxidant induced SEAP release. The present results confirm that prooxidants enhance proinflammatory effects of HMGB1 by activating NF-kappaB through TLR4 signaling. PMID- 26367309 TI - Prospective Optimization with Limited Resources. AB - The future is uncertain because some forthcoming events are unpredictable and also because our ability to foresee the myriad consequences of our own actions is limited. Here we studied how humans select actions under such extrinsic and intrinsic uncertainty, in view of an exponentially expanding number of prospects on a branching multivalued visual stimulus. A triangular grid of disks of different sizes scrolled down a touchscreen at a variable speed. The larger disks represented larger rewards. The task was to maximize the cumulative reward by touching one disk at a time in a rapid sequence, forming an upward path across the grid, while every step along the path constrained the part of the grid accessible in the future. This task captured some of the complexity of natural behavior in the risky and dynamic world, where ongoing decisions alter the landscape of future rewards. By comparing human behavior with behavior of ideal actors, we identified the strategies used by humans in terms of how far into the future they looked (their "depth of computation") and how often they attempted to incorporate new information about the future rewards (their "recalculation period"). We found that, for a given task difficulty, humans traded off their depth of computation for the recalculation period. The form of this tradeoff was consistent with a complete, brute-force exploration of all possible paths up to a resource-limited finite depth. A step-by-step analysis of the human behavior revealed that participants took into account very fine distinctions between the future rewards and that they abstained from some simple heuristics in assessment of the alternative paths, such as seeking only the largest disks or avoiding the smaller disks. The participants preferred to reduce their depth of computation or increase the recalculation period rather than sacrifice the precision of computation. PMID- 26367310 TI - Reduced NOV/CCN3 Expression Limits Inflammation and Interstitial Renal Fibrosis after Obstructive Nephropathy in Mice. AB - The main hallmark of chronic kidney disease (CKD) is excessive inflammation leading to interstitial tissue fibrosis. It has been recently reported that NOV/CCN3 could be involved in kidney damage but its role in the progression of nephropathies is poorly known. NOV/CCN3 is a secreted multifunctional protein belonging to the CCN family involved in different physiological and pathological processes such as angiogenesis, inflammation and cancers. The purpose of our study was to determine the role of NOV/CCN3 in renal inflammation and fibrosis related to primitive tubulointerstitial injury. After unilateral ureteral obstruction (UUO), renal histology and real-time PCR were performed in NOV/CCN3-/ and wild type mice. NOV/CCN3 mRNA expression was increased in the obstructed kidneys in the early stages of the obstructive nephropathy. Interestingly, plasmatic levels of NOV/CCN3 were strongly induced after 7 days of UUO and the injection of recombinant NOV/CCN3 protein in healthy mice significantly increased CCL2 mRNA levels. Furthermore, after 7 days of UUO NOV/CCN3-/- mice displayed reduced proinflammatory cytokines and adhesion markers expression leading to restricted accumulation of interstitial monocytes, in comparison with their wild type littermates. Consequently, in NOV/CCN3-/- mice interstitial renal fibrosis was blunted after 15 days of UUO. In agreement with our experimental data, NOV/CCN3 expression was highly increased in biopsies of patients with tubulointerstitial nephritis. Thus, the inhibition of NOV/CCN3 may represent a novel target for the progression of renal diseases. PMID- 26367311 TI - Social Regulation of Gene Expression in Threespine Sticklebacks. AB - Identifying genes that are differentially expressed in response to social interactions is informative for understanding the molecular basis of social behavior. To address this question, we described changes in gene expression as a result of differences in the extent of social interactions. We housed threespine stickleback (Gasterosteus aculeatus) females in either group conditions or individually for one week, then measured levels of gene expression in three brain regions using RNA-sequencing. We found that numerous genes in the hindbrain/cerebellum had altered expression in response to group or individual housing. However, relatively few genes were differentially expressed in either the diencephalon or telencephalon. The list of genes upregulated in fish from social groups included many genes related to neural development and cell adhesion as well as genes with functions in sensory signaling, stress, and social and reproductive behavior. The list of genes expressed at higher levels in individually-housed fish included several genes previously identified as regulated by social interactions in other animals. The identified genes are interesting targets for future research on the molecular mechanisms of normal social interactions. PMID- 26367312 TI - Impact of malocclusion on affective/romantic relationships among young adults. AB - OBJECTIVE: To evaluate the extent to which different types of malocclusion influence the development of affective/romantic relationships among young adults of both sexes. MATERIALS AND METHODS: A cross-sectional study was conducted with 360 men and women ranging in age from 18 years to 25 years. Criteria for exclusion from the sample were the following: participants could not be married, visually impaired, or students of a higher education course in the area of health. In this study, images of young adult men and women in the same age range as that of the evaluators were used. These images were manipulated to create different types of malocclusion: diastema, open bite, crowding, gingival (or gummy) smile, little exposure of teeth. Six groups of images containing six images each were formed and consisted of two experimental images (digitally manipulated) and four control images. These images were provided to the participants, who evaluated them by means of a questionnaire and a visual analog scale. The Kruskal-Wallis, Mann-Whitney, chi-square, and Fisher exact tests were used for data analysis. RESULTS: All malocclusions had a negative impact on acceptance by the evaluators for the purposes of affective/romantic relationships, with crowding being the type of malocclusion that led to the highest level of rejection (P < .01). CONCLUSION: Malocclusions have a negative influence on the development of affective/romantic relationships among young adults. Individuals with good occlusion are seen in a more positive light, from the perspective of affective life. PMID- 26367313 TI - Effects of fixed labial orthodontic appliances on speech sound production. AB - OBJECTIVE: To explore the impact of fixed labial orthodontic appliances on speech sound production. MATERIALS AND METHODS: Speech evaluations were performed on 23 patients with fixed labial appliances. Evaluations were performed immediately prior to appliance insertion, immediately following insertion, and 1 and 2 months post insertion. Baseline dental/skeletal variables were correlated with the ability to accommodate the presence of the appliances. RESULTS: Appliance effects were variable: 44% of the subjects were unaffected, 39% were temporarily affected but adapted within 2 months, and 17% of patients showed persistent sound errors at 2 months. Resolution of acquired sound errors was noted by 8 months post appliance removal. Maladaptation to appliances was correlated to severity of malocclusion as determined by the Grainger's Treatment Priority Index. Sibilant sounds, most notably /s/, were affected most often. CONCLUSIONS: (1) Insertion of fixed labial appliances has an effect on speech sound production. (2) Sibilant and stopped sounds are affected, with /s/ being affected most often. (3) Accommodation to fixed appliances depends on the severity of malocclusion. PMID- 26367314 TI - Effect of mode of delivery on vertical human papillomavirus transmission - A meta analysis. AB - A systematic review of the literature has been conducted (last update March 2014) for clinical studies reporting the prevalence of human papillomavirus (HPV) in the offspring of HPV-infected women in association to their mode of delivery. A meta-analysis was carried out according to the identification of concordant neonatal to maternal HPV types. Overall eight studies were included in the meta analysis. Our pooled results, showed that caesarean section is associated with significantly lower rates of HPV transmission than vaginal birth (14.9% vs. 28.2%, risk ratio or RR: 0.515, 95% confidence interval or CI: 0.34-0.78). The number of caesarean sections needed to prevent one case of perinatal infection (number needed to treat or NNT) would be 7.5. As a conclusion it should be noted that caesarean section decreases the risk for perinatal HPV transmission by approximately 46%. Perinatal transmission still occurs in approximately 15% of the children born by caesarean section. PMID- 26367315 TI - Comparison of the COPD Assessment Test (CAT) and the Clinical COPD Questionnaire (CCQ) in a Clinical Population. AB - INTRODUCTION: The COPD Assessment Test (CAT) and the Clinical COPD Questionnaire (CCQ) are both clinically useful health status instruments. The main objective was to compare CAT and CCQ measurement instruments. METHODS: CAT and CCQ forms were completed by 432 randomly selected primary and secondary care patients with a COPD diagnosis. Correlation and linear regression analyses of CAT and CCQ were performed. Standardised scores were created for the CAT and CCQ scores, and separate multiple linear regression analyses for CAT and CCQ examined associations with sex, age (<= 60, 61-70 and >70 years), exacerbations (>= 1 vs 0 in the previous year), body mass index (BMI), heart disease, anxiety/depression and lung function (subgroup with n = 246). RESULTS: CAT and CCQ correlated well (r = 0.88, p < 0.0001), as did CAT >= 10 and CCQ >= 1 (r = 0.78, p < 0.0001). CCQ 1.0 corresponded to CAT 9.93 and CAT 10 to CCQ 1.29. Both instruments were associated with BMI < 20 (standardised adjusted regression coefficient (95%CI) for CAT 0.56 (0.18 to 0.93) and CCQ 0.56 (0.20 to 0.92)), exacerbations (CAT 0.77 (0.58 to 0.95) and CCQ 0.94 (0.76 to 1.12)), heart disease (CAT 0.38 (0.17 to 0.59) and CCQ 0.23 (0.03 to 0.43)), anxiety/depression (CAT 0.35 (0.15 to 0.56) and CCQ 0.41 (0.21 to 0.60)) and COPD stage (CAT 0.19 (0.05 to 0.34) and CCQ 0.22 (0.07 to 0.36)). CONCLUSIONS: CAT and CCQ correlate well with each other. Heart disease, anxiety/depression, underweight, exacerbations, and low lung function are associated with worse health status assessed by both instruments. PMID- 26367316 TI - Glutathione deficiency attenuates endotoxic fever in rats. AB - PURPOSE: Glutathione constitutes the first line of the cellular defence mechanism against oxidative stress, and according to published data it is required by a number of factors that are involved in fever mechanism. The aim of the present study was to investigate whether or not glutathione deficiency can modulate a course of the fever induced by endotoxin (LPS). MATERIAL AND METHODS: Intraperitoneal injection of LPS from Escherichia coli was used to provoke fever in Wistar rats. The level of liver glutathione was decreased by administration of phorone (Pho). Deep body temperature (Tb) in free running rats was recorded using a biotelemetry system. The concentration of TNF-alpha was estimated. Next, the supplementation of TNF-alpha was done using recombinant rat TNF-alpha. RESULTS: Animals with decreased glutathione level responded with diminished fever after LPS injection (average Tb in Pho/LPS-treated and oil/LPS-treated animals were 36.90 degrees +/- 0.10 degrees C and 37.80 degrees +/- 0.15 degrees C, respectively). This response was accompanied by a significant attenuation of LPS induced increase in TNF-alpha concentration (in the Pho/LPS-treated group it was 10.68 pg/mL +/- 2.24, vs. 113.35 pg/mL +/- 13.93 in oil/LPS-treated rats). Supplementation with TNF-alpha partially restored fever. CONCLUSION: Based on these data, we conclude that glutathione deficiency modifies the LPS-induced fever, in a TNF-alpha related manner. PMID- 26367319 TI - Case report: A rare case of eccrine carcinoma. AB - INTRODUCTIONS: Sweat gland carcinoma is very rare with a reported incidence of less than 0.005% of all tumour specimens resected surgically (Tulenko and Conway, 1965) [1]. CASE REPORT: A sixty year old male patient presented to us with a solitary swelling over the left chest wall since two months. DISCUSSION: Cutaneous apocrine gland carcinoma, a subtype of sweat gland carcinoma, is a very rare malignant neoplasm arising in areas of high apocrine sweat gland density. The variability of the histological features even in the same tumour, and its rarity, have contributed to some confusion regarding the classification of sweat gland carcinoma. CONCLUSIONS: Sweat gland carcinomas are a rare group of tumours with potential for local destruction as well as distant metastasis. Wide surgical excision along with regional lymph node dissection in the presence of clinically positive nodes is the recommended treatment. However, a frequent follow up is essential to detect early recurrence as well as distant metastasis. PMID- 26367317 TI - Long-Term Results of Concurrent Chemoradiotherapy for Advanced N2-3 Stage Nasopharyngeal Carcinoma. AB - BACKGROUND: N-stage is related to distant metastasis in nasopharyngeal carcinoma (NPC) patients. The purpose of this study was to evaluate the efficacy and toxicity of different nedaplatin-based chemotherapy regimens in advanced N2-3 stage NPC patients treated with intensity modulated radiation therapy (IMRT). PATIENTS AND METHODS: Between April 2005 and December 2009, a total of 128 patients with N2-3 advanced NPC were retrospectively analyzed. Patients were treated with IMRT concurrent with 2 cycles of chemotherapy consisting of either nedaplatin plus paclitaxel (NP group, n = 67) or nedaplatin plus fluorouracil and paclitaxel (NFP group, n = 61). Two to four cycles of adjuvant chemotherapy were then administered every 21 days following concurrent chemoradiotherapy. RESULTS: With a median follow-up of 60 months, the 5-year overall survival (OS), progression-free survival (PFS), local-regional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) for all patients were 81.4%, 71.5%, 87.8% and 82.0%, respectively. No significant difference in PFS (66.6% vs. 76.7%, P = 0.212) and LRRFS rates (89.0% vs. 86.3%, P = 0.664) was observed between the NP and NFP groups. The 5-year OS (75.4% vs. 88.5%, P = 0.046) and DMFS (75.1% vs. 89.0%, P = 0.042) rate were superior in the NFP group compared with the NP group. The NFP group had a higher incidence of grade 3-4 acute toxicities including bone marrow suppression (leukopenia: chi2 = 3.935, P = 0.047; anemia: chi2 = 9.760, P = 0.002; thrombocytopenia: chi2 = 8.821, P = 0.003), and both liver and renal dysfunction (chi2 = 5.206, P = 0.023) compared with the NP group. Late toxicities were moderate and no difference was observed between the two groups. CONCLUSION: IMRT concurrent with nedaplatin-based chemotherapy is an advocated regimen for patients with advanced N2-3 stage NPC. Patients with advanced N2-3 stage may be better candidates for the NFP regimen although this regimen was associated with a high acute toxicity rate. PMID- 26367320 TI - DLA based compressed sensing for high resolution MR microscopy of neuronal tissue. AB - In this work we present the implementation of compressed sensing (CS) on a high field preclinical scanner (17.2 T) using an undersampling trajectory based on the diffusion limited aggregation (DLA) random growth model. When applied to a library of images this approach performs better than the traditional undersampling based on the polynomial probability density function. In addition, we show that the method is applicable to imaging live neuronal tissues, allowing significantly shorter acquisition times while maintaining the image quality necessary for identifying the majority of neurons via an automatic cell segmentation algorithm. PMID- 26367321 TI - Air core notch-coil magnet with variable geometry for fast-field-cycling NMR. AB - In this manuscript we present details on the optimization, construction and performance of a wide-bore (71 mm) alpha-helical-cut notch-coil magnet with variable geometry for fast-field-cycling NMR. In addition to the usual requirements for this kind of magnets (high field-to-power ratio, good magnetic field homogeneity, low inductance and resistance values) a tunable homogeneity and a more uniform heat dissipation along the magnet body are considered. The presented magnet consists of only one machined metallic cylinder combined with two external movable pieces. The optimal configuration is calculated through an evaluation of the magnetic flux density within the entire volume of interest. The magnet has a field-to-current constant of 0.728 mT/A, allowing to switch from zero to 0.125 T in less than 3 ms without energy storage assistance. For a cylindrical sample volume of 35 cm(3) the effective magnet homogeneity is lower than 130 ppm. PMID- 26367323 TI - Role of MRI in the diagnosis and management of prostate cancer. AB - Multiparametric MRI of the prostate consists of T1- and T2-weighted sequences, which provide anatomical information, and one or more 'functional' sequences, that is, diffusion-weighted imaging, dynamic contrast-enhanced sequences and magnetic resonance spectroscopy. Prostate MRI is the most accurate imaging method for local staging of prostate cancer and can also be used for the noninvasive evaluation of tumor aggressiveness. By magnetic resonance-guided prostate biopsy it is possible to target the most cancer-suspicious areas of the gland, especially in patients with a negative transrectal biopsy. In patients with biochemical recurrence after radical treatment, MRI is a valuable tool for the detection of local tumor recurrence and whole-body MRI can be used for the diagnosis of distant metastases. PMID- 26367324 TI - Interleukin-24 inhibits influenza A virus replication in vitro through induction of toll-like receptor 3 dependent apoptosis. AB - New anti-viral agents and strategies are urgently needed to fight rapidly mutating viruses, as vaccine programs cannot react fast enough to prevent pandemics. Recently, we have shown that interleukin-24 (IL-24) sensitizes tumor cells to toll-like receptor 3 (TLR3) mediated apoptosis. As influenza A virus stimulates the TLR3 receptor, we hypothesized that IL-24 might also exert an anti viral effect. This study demonstrates that IL-24 reduces the titer of different influenza A virus subtypes independently of type I interferon in an apoptosis dependent manner. The anti-viral effect of IL-24 correlated with caspase-3 activation and could be blocked by a pan-caspase inhibitor and by small interfering RNA (siRNA) directed towards TLR3. Surprisingly, caspase-3 activation in influenza A virus/IL-24-stimulated cells correlated with the down-regulation of the B-cell lymphoma 2 (Bcl-2) family member myeloid cell leukemia 1 (Mcl-1). Correspondingly, knockdown of Mcl-1 by siRNA enhanced caspase activation in influenza A virus infected cells and was furthermore linked to a reduction of viral titers. We conclude that IL-24 exerts an anti-viral role selectively purging virally infected cells by leading to a down-regulation of Mcl-1. Our findings might therefore represent the first step towards a new rational concept in the development of anti-viral strategies based on the induction of apoptosis. PMID- 26367322 TI - (15)N CSA tensors and (15)N-(1)H dipolar couplings of protein hydrophobic core residues investigated by static solid-state NMR. AB - In this work, we assess the usefulness of static (15)N NMR techniques for the determination of the (15)N chemical shift anisotropy (CSA) tensor parameters and (15)N-(1)H dipolar splittings in powder protein samples. By using five single labeled samples of the villin headpiece subdomain protein in a hydrated lyophilized powder state, we determine the backbone (15)N CSA tensors at two temperatures, 22 and -35 degrees C, in order to get a snapshot of the variability across the residues and as a function of temperature. All sites probed belonged to the hydrophobic core and most of them were part of alpha helical regions. The values of the anisotropy (which include the effect of the dynamics) varied between 130 and 156 ppm at 22 degrees C, while the values of the asymmetry were in the 0.32-0.082 range. The Leu-75 and Leu-61 backbone sites exhibited high mobility based on the values of their temperature-dependent anisotropy parameters. Under the assumption that most differences stem from dynamics, we obtained the values of the motional order parameters for the (15)N backbone sites. While a simple one-dimensional line shape experiment was used for the determination of the (15)N CSA parameters, a more advanced approach based on the "magic sandwich" SAMMY pulse sequence (Nevzorov and Opella, 2003) was employed for the determination of the (15)N-(1)H dipolar patterns, which yielded estimates of the dipolar couplings. Accordingly, the motional order parameters for the dipolar interaction were obtained. It was found that the order parameters from the CSA and dipolar measurements are highly correlated, validating that the variability between the residues is governed by the differences in dynamics. The values of the parameters obtained in this work can serve as reference values for developing more advanced magic-angle spinning recoupling techniques for multiple labeled samples. PMID- 26367325 TI - Interdisciplinary therapy changes superoxide dismutase activity and adiponectin in obese adolescents: a randomised controlled trial. AB - The objective of this study is to evaluate the effect of interdisciplinary therapy in the parameters of the oxidative stress and the anti-inflammatory responses of obese adolescents. We selected 57 participants, who were randomly divided into 2 groups: interdisciplinary therapy group and a control group. After 6 months of intervention, 17 participants of the interdisciplinary therapy group and 8 of the control group returned for re-evaluation. The interdisciplinary therapy group participated in a treatment with 4 weekly sessions of exercise, a weekly group therapy session and a weekly nutritional education session. Blood parameters of oxidative stress and anti-inflammatory response were evaluated. The results demonstrated that there were significant increases in the interdisciplinary therapy group for superoxide dismutase activity (6.56 +/- 3.22 to 11.40 +/- 7.49) and ferric-reducing antioxidant potential concentration (532.91 +/- 106.48 to 573.25 +/- 112.57), although adiponectin levels did not reduce (40.9 +/- 29.34 to 49.05 +/- 41.22). A significant decrease in nitrite levels was also found (14.23 +/- 8.48 to 11.45 +/- 6.05). In the control group, significant reduction was found in adiponectin (31.56 +/- 18.88 to 18.01 +/- 11.66). This study suggests that interdisciplinary therapy for 6 months was effective in improving the anti-inflammatory responses and the antioxidant defences in obese adolescents. PMID- 26367326 TI - KPNA3-knockdown eliminates the second heat shock protein peak associated with the heat shock response of male silkworm pupae (Bombyx mori) by reducing heat shock factor transport into the nucleus. AB - In this study, we investigated the role of karyopherin alpha 3 in the heat shock response in male silkworm pupae. Karyopherin alpha recognizes the classical nuclear location sequence on proteins and transports them into the nucleus by forming a trimetric complex with karyopherin beta. Three predicted karyopherin alphas (KPNA1, KPNA2 and KPNA3) have been identified from the silkworm Bombyx mori. Pull-down assay result showed that KPNA3 can pull down heat shock transcription factor (HSF) from proteins extracted from tissues using non denature lysis buffer. After 45 degrees C heat shock on male B. mori pupae for 30 min, we identified two heat shock protein (HSP) mRNA expression peaks correlating with HSP19.9, HSP20.4 and HSP25.4 at 4 h (peak 1) and 24 h (peak 2). The second peak was eliminated after knockdown of KPNA3. Similar results were obtained following knockdown of HSF, which is the trans-activating factor of heat shock. However, KPNA3 knockdown was not accompanied by the decreased HSF protein levels at 24 h after heat shock which were observed following HSF knockdown. We also expressed recombinant protein GST-KPNA3 and His-HSF in Escherichia coli to perform GST pull-down assay and the result confirmed the interaction between KPNA3 and HSF. We concluded that KPNA3 knockdown eliminates the second heat shock protein peak in the heat shock response of male silkworm pupae by reducing HSF transport into the nucleus. PMID- 26367327 TI - Molecular characterization of a novel ovary-specific gene fem-1 homolog from the oriental river prawn, Macrobrachium nipponense. AB - The feminization-1 (fem-1) gene is characterized by one of the most common protein-protein interaction motifs, ankyrin repeat motifs, displays many expression patterns in vertebrates and invertebrates, and plays an essential role in the sex-determination/differentiation pathway in Caenorhabditis elegans. In this study, a fem-1 homolog, designated as Mnfem-1, was first cloned from the oriental river prawn Macrobrachium nipponense. The prawn Mnfem-1 gene consists of six exons and five introns. The full-length cDNA (2603bp) of Mnfem-1 contains an open reading frame (ORF) encoding a protein of 622 amino acids. The Mnfem-1 RNA and protein are exclusively expressed in the ovary in adult prawns as revealed by RT-PCR and immunofluorescence analysis, respectively. In situ hybridization results showed that strong positive signals were concentrated at the edge of the previtellogenic and vitellogenic oocyte. During embryogenesis, Mnfem-1 is highly expressed in both unfertilized eggs and embryos at cleavage stage and thereafter dropped to a low level from blastula to zoea, indicating that the Mnfem-1 in early embryos is maternal. After hatching, the Mnfem-1 expression significantly increased in the larvae at length of 2cm, an important stage of sex differentiation. Yeast two hybridization results showed that the Mnfem-1 protein can be potentially interactive with cathepsin L and proteins containing the domains of insulinase, ankyrin or ubiquitin. Our results suggested that Mnfem-1 could have roles in prawn ovarian development and sex determination/differentiation. PMID- 26367328 TI - Alteration of gene expression in MDA-MB-453 breast cancer cell line in response to continuous exposure to Trastuzumab. AB - Development of resistance against cancer therapeutic agents is a common problem in cancer management. Trastuzumab resistance is one of the challenges in management of HER-2-positive breast cancer patients resulting in breast cancer progression, metastasis, and patient poor outcome. The aim of this study is to determine the alteration in gene expression in response to Trastuzumab resistance after long-term exposure to Trastuzumab. The Trastuzumab-resistant MDA-MB-453 (MDA-MB-453/TR) cell line was developed by exposing cells to 10 MUM Trastuzumab continuously for 6 months. Sensitivity toward Trastuzumab was tested using cell viability assays. The acquisition of an epithelial-to mesenchymal transition (EMT) phenotype was also observed in parallel with the development of resistance. Based on the real-time-based PCR array technology, several genes were altered affecting multiple networks. The most up-regulated genes were TGF-beta1 and EGF, and IGFBP-3. These genes are known to have a critical role in Trastuzumab resistance in breast cancer cell lines and/or in the acquisition of EMT. They are also recognized for their role in cancer progression and metastasis. These alterations indicate that the development of Trastuzumab resistance is multifactorial and involves a development of a mesenchymal like phenotype. PMID- 26367329 TI - A novel periplasmic protein (Slr0280) tunes photomixotrophic growth of the cyanobacterium, Synechocystis sp. PCC 6803. AB - Cyanobacteria are among the main contributors to global photosynthesis and show a high degree of metabolic plasticity. Synechocystis sp. PCC 6803 can grow under photoautotrophic, photomixotrophic or photoheterotrophic conditions. We have characterized a novel periplasmic protein (Slr0280) that tunes the photomixotrophic growth of Synechocystis sp. PCC 6803. Slr0280 is a multi-domain protein consisting mainly of beta-sheets. Several proteins that interact with Slr0280 were identified via bacterial two-hybrid screening. Slr0280 may interact through its DUF2233 domain with partners that participate in sugar metabolism, thereby coordinating the respective regulations. When slr0280 was deleted, the mutant grew more slowly than wild-type in the presence of glucose, which is ascribed to the down-regulation of glycolysis, glycogen catabolism, oxidative pentose phosphate pathway, Calvin cycle and glucose utilization. A positive regulation of Slr0280 on these sugar catabolic enzymes was confirmed by transcript (qPCR) analyses. Based on these findings, we proposed a speculative model that Slr0280 plays a coordinating regulatory role in sugar metabolism. PMID- 26367330 TI - Identification and biochemical characterization of polyamine oxidases in amphioxus: Implications for emergence of vertebrate-specific spermine and acetylpolyamine oxidases. AB - Polyamine oxidases (PAOs) have been identified in a wide variety of animals, as well as in fungi and plant. Generally, plant PAOs oxidize spermine (Spm), spermidine (Spd) and their acetylated derivatives, N(1)-acetylspermine (N(1) Aspm) and N(1)-acetylspermidine (N(1)-Aspd), while yeast PAOs oxidize Spm, N(1) Aspm and N(1)-Aspd, but not Spd. By contrast, two different enzymes, namely spermine oxidase (SMO) and acetylpolyamine oxidase (APAO), specifically catalyze the oxidation of Spm and N(1)-Aspm/N(1)-Aspd, respectively. However, our knowledge on the biochemical and structural characterization of PAOs remains rather limited, and their evolutionary history is still enigmatic. In this study, two amphioxus (Branchiostoma japonicum) PAO genes, named Bjpao1 and Bjpao2, were cloned and characterized. Both Bjpao1 and Bjpao2 displayed distinct tissue specific expression patterns. Notably, rBjPAO1 oxidized both spermine and spermidine, but not N(1)-acetylspermine, whereas rBjPAO2 oxidizes both spermidine and N(1)-acetylspermine, but not spermine. To understand structure-function relationship, the enzymatic activities of mutant BjPAOs that were generated by site-directed mutagenesis and expressed in E. coli were examined, The results indicate that the residues H64, K301 and T460 in rBjPAO1, and H69, K315 and T467 in rBjPAO2 were all involved in substrate binding and enzyme catalytic activity to some extent. Based on our results and those of others, a model depicting the divergent evolution and functional specialization of vertebrate SMO and APAO genes is proposed. PMID- 26367331 TI - Whey Protein Concentrate Hydrolysate Prevents Bone Loss in Ovariectomized Rats. AB - Milk is known as a safe food and contains easily absorbable minerals and proteins, including whey protein, which has demonstrated antiosteoporotic effects on ovariectomized rats. This study evaluated the antiosteoporotic effect of whey protein concentrate hydrolysate (WPCH) digested with fungal protease and whey protein concentrate (WPC). Two experiments were conducted to determine (1) efficacy of WPCH and WPC and (2) dose-dependent impact of WPCH in ovariectomized rats (10 weeks old). In Experiment I, ovariectomized rats (n=45) were allotted into three dietary treatments of 10 g/kg diet of WPC, 10 g/kg diet of WPCH, and a control diet. In Experiment II, ovariectomized rats (n=60) were fed four different diets (0, 10, 20, and 40 g/kg of WPCH). In both experiments, sham operated rats (n=15) were also fed a control diet containing the same amount of amino acids and minerals as dietary treatments. After 6 weeks, dietary WPCH prevented loss of bone, physical properties, mineral density, and mineral content, and improved breaking strength of femurs, with similar effect to WPC. The bone resorption enzyme activity (tartrate resistance acid phosphatase) in tibia epiphysis decreased in response to WPCH supplementation, while bone formation enzyme activity (alkaline phosphatase) was unaffected by ovariectomy and dietary treatment. Bone properties and strength increased as the dietary WPCH level increased (10 and 20 g/kg), but there was no difference between the 20 and 40 g/kg treatment. WPCH and WPC supplementation ameliorated bone loss induced by ovariectomy in rats. PMID- 26367333 TI - Environmental Standards Shape the Future of Technology. PMID- 26367332 TI - The complete chloroplast genome sequence of Curcuma flaviflora (Curcuma). AB - The complete chloroplast (cp) genome of Curcuma flaviflora, a medicinal plant in Southeast Asia, was sequenced. The genome size was 160 478 bp in length, with 36.3% GC content. A pair of inverted repeats (IRs) of 26 946 bp were separated by a large single copy (LSC) of 88 008 bp and a small single copy (SSC) of 18 578 bp, respectively. The cp genome contained 132 annotated genes, including 79 protein coding genes, 30 tRNA genes, and four rRNA genes. And 19 of these genes were duplicated in inverted repeat regions. PMID- 26367334 TI - The clinical utility of reticular basement membrane thickness measurements in asthmatic children. AB - OBJECTIVE: Reticular basement membrane (RBM) thickness is one of the pathological features of asthma and can be measured in endobronchial biopsies. We assessed the feasibility of endobronchial biopsies in a routine clinical setting and investigated the clinical value of RBM thickness measurements for asthma diagnosis in children. METHODS: We included all children who underwent bronchoscopy with endobronchial mucosal biopsies for clinical reasons and divided them into three subgroups: (1) no asthma, (2) mild-moderate asthma, and (3) problematic severe asthma. RESULTS: In 152/214 (71%) patients, mean age 9.5 years (SD 4.6; range 0.1-18.7) adequate biopsies were retrieved in which RBM thickness could be measured. Mean (SD) RBM thickness differed significantly among children without asthma, with mild-moderate asthma, and with problematic severe asthma (p = 0.04), 4.68 (1.24) um, 4.56 (0.89) um, and 5.21 (1.10) um respectively. This difference disappeared after adding exhaled nitric oxide to the multivariate model. CONCLUSIONS: This study confirms the difference in RBM thickness between children with and without asthma and between asthma severities in a routine clinical care setting. However, quantifying the RBM thickness appeared to have no added clinical diagnostic value for asthma in children. PMID- 26367336 TI - Does "smoker's paradox" exist in clopidogrel-treated Turkish patients with acute coronary syndrome. AB - Previously conducted studies revealed that smoking enhanced the efficacy of clopidogrel by increasing formation of the active metabolite (AM) from the prodrug through induction of the cytochrome CYP1A2. The expression of cytochrome enzymes depends on genotype and no data exists in literature conducted in Turkish patients comparing the clopidogrel responsiveness between active smokers and non active smokers treated with clopidogrel. In this study, our aim was to investigate the clopidogrel responsiveness in clopidogrel-treated Turkish acute coronary syndrome (ACS) patients according to their smoking status. We retrospectively enrolled 258 patients who were hospitalized due to ACS. Clinical variables of the patients, especially smoking status were recorded. Clopidogrel resistance was evaluated by using adenosine diphosphate (ADP) induced platelet aggregometry. Clopidogrel resistance was detected as a change in maximal aggregation <=20% from baseline. A total of 139 patients were active smokers while 12 were former smokers. 107 patients did not have a history of smoking. Ten of the smokers were hyporesponsive to clopidogrel, whereas 36 of non-smokers were hyporesponsive to clopidogrel (p < 0.001). Receiver-operating characteristic curve analysis demonstrated that Au-min value >612.5 predicted the clopidogrel resistance with a sensitivity of 60% (OR: 100.65, %95 CI = 19.996-506.615 p < 0.001). Results of this study demonstrated that ADP responses were lower in smokers receiving clopidogrel and aspirin than in non-smokers receiving the same drug regimen. This finding indicates that smoking was related to an enhanced clopidogrel responsiveness in Turkish patients hospitalized due to ACS, suggesting that "smoker's paradox" probably exists in Turkish ACS patients. PMID- 26367337 TI - Comparison of Two- and Three-Dimensional Methods for Analysis of Trunk Kinematic Variables in the Golf Swing. AB - Two-dimensional methods have been used to compute trunk kinematic variables (flexion/extension, lateral bend, axial rotation) and X-factor (difference in axial rotation between trunk and pelvis) during the golf swing. Recent X-factor studies advocated three-dimensional (3D) analysis due to the errors associated with two-dimensional (2D) methods, but this has not been investigated for all trunk kinematic variables. The purpose of this study was to compare trunk kinematic variables and X-factor calculated by 2D and 3D methods to examine how different approaches influenced their profiles during the swing. Trunk kinematic variables and X-factor were calculated for golfers from vectors projected onto the global laboratory planes and from 3D segment angles. Trunk kinematic variable profiles were similar in shape; however, there were statistically significant differences in trunk flexion (-6.5 +/- 3.6 degrees ) at top of backswing and trunk right-side lateral bend (8.7 +/- 2.9 degrees ) at impact. Differences between 2D and 3D X-factor (approximately 16 degrees ) could largely be explained by projection errors introduced to the 2D analysis through flexion and lateral bend of the trunk and pelvis segments. The results support the need to use a 3D method for kinematic data calculation to accurately analyze the golf swing. PMID- 26367335 TI - The early origins of obesity and insulin resistance: timing, programming and mechanisms. AB - Maternal obesity is associated with an increased risk of developing gestational diabetes mellitus and it also results in an increased risk of giving birth to a large baby with increased fat mass. Furthermore, it is also contributes to an increased risk of obesity and insulin resistance in the offspring in childhood, adolescence and adult life. It has been proposed that exposure to maternal obesity may therefore result in an 'intergenerational cycle' of obesity and insulin resistance. There is significant interest in whether exposure to maternal obesity around the time of conception alone contributes directly to poor metabolic outcomes in the offspring and whether dieting in the obese mother before pregnancy or around the time of conception has metabolic benefits for the offspring. This review focusses on experimental and clinical studies that have investigated the specific impact of exposure to maternal obesity during the periconceptional period alone or extending beyond conception on adipogenesis, lipogenesis and on insulin signalling pathways in the fat, liver and muscle of the offspring. Findings from these studies highlight the need for a better evidence base for the development of dietary interventions in obese women before pregnancy and around the time of conception to maximize the metabolic benefits and minimize the metabolic costs for the next generation. PMID- 26367338 TI - Renal colic: current protocols for emergency presentations. AB - Flank pain caused by renal colic is a common presentation to emergency departments. This paper reviews the acute clinical assessment of these patients, outlines appropriate diagnostic strategies with labwork and imaging and updates the reader on conservative treatments, suitable choices for analgesia and indications for surgical intervention. Prompt diagnosis and appropriate treatment instituted in the Emergency Department can rapidly and effectively manage this excruciatingly painful condition. PMID- 26367339 TI - Correction: Native architecture of the Chlamydomonas chloroplast revealed by in situ cryo-electron tomography. PMID- 26367340 TI - Intravitreal Bevacizumab for Traumatic Choroidal Rupture. AB - PURPOSE: To report a case of visual loss associated with traumatic choroidal rupture after blunt ocular trauma that was successfully treated with an early intravitreal bevacizumab injection despite the absence of choroidal neovascularization (CNV). CASE REPORT: A 14-year-old boy presented with visual disturbance in his left eye after sustaining an ocular contusion 4 weeks earlier. The best-corrected visual acuity (BCVA) in the left eye was 20/50. Funduscopic examination revealed macular choroidal rupture accompanied by subretinal hemorrhage. Optical coherence tomography (OCT) showed accumulation of subretinal fluid around a disrupted retinal pigment epithelium/Bruch membrane complex extending into the juxtafoveolar area, but there was no active leakage suggestive of CNV on fluorescein angiography. Intravitreal bevacizumab (1.25 mg) injection was performed to treat persistent serous retinal detachment at macula causing visual loss. There was a reduction of subretinal fluid and concomitant improvement of BCVA to 20/30 within 1 week after intravitreal bevacizumab injection. The BCVA recovered to 20/25 in the left eye after 4 weeks, and only a minimal amount of residual fluid remained according to OCT. Complete resolution of subretinal fluid was observed by OCT at the 6-week follow-up examination, and BCVA improved to 20/20. Good visual acuity (20/20) and stable macula were maintained in the left eye at 1 year of follow-up without recurrence of subretinal fluid accumulation or hemorrhage and CNV. There were no ocular or systemic complications associated with intravitreal bevacizumab injection. CONCLUSIONS: Early intravitreal bevacizumab injection could be an effective treatment option for patients with vision loss associated with traumatic choroidal rupture and subretinal fluid within the posterior pole before development of CNV. PMID- 26367341 TI - Perceptions of Older People Regarding Their Vision and Incident Causation. AB - PURPOSE: It is widely known that visual impairment (VI) is a risk factor for falls, but patients or their eye care practitioners may not recognize other kinds of incidents as being problematic because of their vision. Consequently, older people with VI may have unmet needs for advice on how to carry out activities of daily living safely. Therefore, the purpose of this study was to understand whether older people with VI consider their vision as a causative factor of incidents they experience and their perceptions regarding the prevention of future incidents. If sample size permitted, a secondary aim was to evaluate whether quantitative findings supported their perceptions. METHODS: The study design was a prospective cohort study evaluating injurious and damaging incidents and related near misses using open questions in a written 2-weekly large-print diary with active follow-up over 8 weeks in older people (>60 years, n = 80) with and without VI. Baseline measures included habitual binocular visual acuity, contrast sensitivity, visual fields, 3-m walk test, and Short Form 12 physical and mental component scores. Participants' diary entries were coded. Factor analysis and binary logistic analysis were used to investigate whether baseline measures were predictive of incident occurrence. Risk and preventative factors identified were compared. RESULTS: Participants perceived that their vision was implicated in bump and fall incidents. Quantitative analysis indicated that contrast sensitivity and fitness were significant predictors of incident occurrence. Six vision-related and five non-vision-related causative factors were identified by participants as contributing factors. Participants frequently stated "don't know" when asked to identify solutions to prevent incident recurrence. CONCLUSIONS: Participants had unmet needs for advice in relation to incident prevention. It would be prudent for eye care practitioners to raise incident prevention in eye care consultations regardless of voiced patient concerns. PMID- 26367343 TI - Neurocognitive Profile of a Woman with Susac's Syndrome: Further Evidence of Cognitive Variability. AB - OBJECTIVE: Susac's syndrome is a rare autoimmune disease characterized by encephalopathy, retinal artery occlusions, hearing loss, and lesions to the corpus callosum. To date, only four papers (five cases) have described the neuropsychological effects of the syndrome. Extant case reports of Susac's syndrome have documented varying levels of cognitive impairment; some studies have identified diffuse cerebral dysfunction, while others describe more focal impairments in attention, memory, and executive functioning. METHOD: The goal of this case study was to provide comprehensive neurocognitive data obtained from another case of confirmed Susac's syndrome. As such, we present the case of a 42 year-old woman with a two-year history of Susac's syndrome. At the time of the neuropsychological evaluation, the patient described ongoing difficulties with memory, word-finding problems, problems with math, and poor problem-solving. Physical/sensory changes included hearing loss, tinnitus, and migraines. RESULTS: Neuropsychological test results revealed the patient to be a woman of estimated average to high average premorbid intellect who exhibited a number of focal inefficiencies in the context of a generally intact profile. Particular cognitive weaknesses emerged on select tasks involving visuoconstruction, encoding of a wordlist, and bilateral speeded finger oscillations. She also committed three failures to maintain set on a task of cognitive flexibility. There was no evidence of memory deficits. CONCLUSIONS: Our findings provide further evidence of cognitive interindividual variability in a confirmed case of Susac's syndrome. PMID- 26367342 TI - Does Older Age Confer an Increased Risk of Incident Neurocognitive Disorders Among Persons Living with HIV Disease? AB - OBJECTIVE: This study aimed to determine the combined effects of age and HIV infection on the risk of incident neurocognitive disorders. METHOD: A total of 146 neurocognitively normal participants were enrolled at baseline into one of four groups based on age (<= 40 years and >= 50 years) and HIV serostatus resulting in 24 younger HIV-, 27 younger HIV+, 39 older HIV-, and 56 older HIV+ individuals. All participants were administered a standardized clinical neuropsychological battery at baseline and 14.3 +/- .2 months later. RESULTS: A logistic regression predicting incident neurocognitive disorders from HIV, age group, and their interaction was significant (chi(2)[4] = 13.56, p = .009), with a significant main effect of HIV serostatus (chi(2)[1] = 5.01, p = .025), but no main effect of age or age by HIV interaction (ps > .10). Specifically, 15.7% of the HIV+ individuals had an incident neurocognitive disorder as compared to 3.2% of the HIV- group (odds ratio = 4.8 [1.2, 32.6]). Among older HIV+ adults, lower baseline cognitive reserve, prospective memory, and verbal fluency each predicted incident neurocognitive disorders at follow-up. CONCLUSIONS: Independent of age, HIV infection confers a nearly fivefold risk for developing a neurocognitive disorder over approximately one year. Individuals with lower cognitive reserve and mild weaknesses in higher-order neurocognitive functions may be targeted for closer clinical monitoring and preventative measures. PMID- 26367344 TI - Population density profiles of nasopharyngeal carriage of 5 bacterial species in pre-school children measured using quantitative PCR offer potential insights into the dynamics of transmission. AB - Bacterial vaccines can reduce carriage rates. Colonization is usually a binary endpoint. Real time quantitative PCR (qPCR) can quantify bacterial DNA in mucosal samples over a wide range. Using culture and single-gene species-specific qPCRs for Streptococcus pneumoniae (lytA), Streptococcus pyogenes (ntpC), Moraxella catarrhalis (ompJ), Haemophilus influenzae (hdp) and Staphylococcus aureus (nuc) and standard curves against log-phase reference strain broth cultures we described frequency and peak density distributions of carriage in nasopharyngeal swabs from 161 healthy 2-4 y old children collected into STGG broth. In general, detection by qPCR and culture was consistent. Discordance mostly occurred at lower detection thresholds of both methods, although PCR assays for S. pyogenes and S. aureus were less sensitive. Density varied across 5-7 orders of magnitude for the 5 species with the abundant species skewed toward high values (modes: S. pneumoniae log3-4, M. catarrhalis & H. influenzae log4-5 CFU/ml broth). Wide ranges of bacterial DNA concentrations in healthy children carrying these bacteria could mean that different individuals at different times vary greatly in infectiousness. Understanding the host, microbial and environmental determinants of colonization density will permit more accurate prediction of vaccine effectiveness. PMID- 26367345 TI - No difference in learning retention in manikin-based simulation based on role. AB - OBJECTIVE: We evaluated learning retention in interns exposed to simulation. It was hypothesized that learning would degrade after 6 months and there would be a difference in retention between interns who played a critical role versus those who did not. METHODS: A total of 23 groups of 5 to 9 interns underwent a cardiac scenario twice during 1 simulation experience and again 6 months later. We captured 69 recordings (23 before debrief at baseline [PrDV], 23 after debrief at baseline [PoDV], and 23 at 6-month follow-up [FUV]). Students were assigned different roles, including the critical role of "doctor" in a blinded, haphazard fashion. At 6-month follow-up, 12 interns who played the role of doctor initially were assigned that role again, while 11 interns who played noncritical roles initially were newly assigned to doctor. All videos of intern performance were scored independently and in a blinded fashion, by 3 judges using a 15-item check list. RESULTS: Repeated-measures analysis of variance for interns completing all 3 time points indicated a significant difference between time points (F2,22 = 112, p = .00). Contrasts showed a statistically significant difference between PrDV and PoDV (p = .00), and PrDV and FUV (p = .00), but no difference between PoDV and FUV (p = .98). This was consistent with results including all data points. Checklist scores were more than double for PoDV recordings (16) and FUV (15), compared to PrDV recordings (6.6). Follow-up scores comparing old to new doctors showed no statistically significant difference (15.4 vs 15.2 respectively, t21 = 0.26, p = .80, d = .11). CONCLUSIONS: Learning retention was maintained regardless of role. PMID- 26367346 TI - High-throughput, big data and complexity in clinical proteomics: an interview with Jasminka Godovac-Zimmermann. AB - Interview with Professor Jasminka Godovac-Zimmermann, PhD by Claire Raison (Commissioning Editor) Professor Jasminka Godovac-Zimmermann is Head of the Proteomics and Molecular Cell Dynamics Group at University College London, UK. Professor Godovac-Zimmermann trained at the Max Planck Institute of Biochemistry, Germany, and specialized in protein chemistry. Her research focuses on proteomics in cancer and systems biology. Here she talks about the clinical impact of her work and her hopes and predictions for how proteomics and diagnostics could work together in future. PMID- 26367348 TI - What do "interpersonally sensitive" supervisors do and how do supervisees experience a relational approach to supervision? AB - OBJECTIVE: In two investigations, we identified explicitly relational supervision strategies and examined whether use of these strategies was associated with perceptions of the supervisory alliance and evaluations of the supervisor. METHOD: First, ratings by nine supervision researchers identified five clearly relational in-session strategies (focus on countertransference, exploration of feelings, attend to parallel process, focus on the therapeutic process, focus on the supervisory alliance) in the Critical Events model of supervision. Based on these expert ratings, we created and assessed the Relational Behavior Scale (RBS). RESULTS: Analyses with two samples of supervisees at all levels of training supported the measure's reliability and factorial validity. The RBS's validity was further indicated by its unique association with the "interpersonally sensitive" style of supervision. In both studies, supervisees perceived more frequent use of relational behavior on the part of psychoanalytic/psychodynamic/humanistic supervisors than cognitive-behavioral supervisors. Moreover, as hypothesized, supervisors' use of relational behavior in a specific session mediated the association between trainees' alliance perceptions and evaluations of their supervisors in that session. CONCLUSION: The identification of specific in-session supervision behaviors that explain one way in which a strong alliance contributes to trainees' positive experiences of their supervisors has implications for supervision theory, research, and practice. PMID- 26367347 TI - SRSF3 and hnRNP H1 regulate a splicing hotspot of HER2 in breast cancer cells. AB - Overexpression of the oncogene HER2 occurs in 20-30% of invasive breast cancer and is associated with poor prognosis. A number of different splice variants of HER2 have been identified which produce functionally different proteins. Previously these splice variants have been investigated separately, but in the present study we collectively look at the expression and regulation of a group of HER2 splice variants produced by a splicing hotspot. Initial investigation in a cohort of tumor samples showed large variations in HER2 variant expression between patient samples. RNA interference studies identified 2 splicing factors involved in the regulation of splicing within this region, hnRNP H1 and SRSF3. siRNA targeting hnRNP H1 increases levels of X5 and the oncogenic variant Delta16HER2. Furthermore RNA chromatography assays demonstrated binding of hnRNP H1 to RNA in this region. Additionally the proto-oncogene SRSF3 was also identified as an important regulator of splicing with SRSF3 knockdown resulting in changes in all the splice variants located at the hotspot. Most notably knockdown of SRSF3 resulted in a switch from the oncogenic Delta16HER2 to p100 which inhibits cell proliferation. Binding of SRSF3 to RNA within this region was also demonstrated by RNA chromatography and more specifically 2 SRSF3 binding sites were identified within exon 15. SRSF3 and hnRNP H1 are the first splicing factors identified which regulate the production of these functionally distinct HER2 splice variants and therefore maybe important for the regulation of HER2 signaling. PMID- 26367349 TI - Notice of Retraction: Ahimastos AA, et al. Effect of Ramipril on Walking Times and Quality of Life Among Patients With Peripheral Artery Disease and Intermittent Claudication: A Randomized Controlled Trial. JAMA. 2013;309(5):453 460. PMID- 26367351 TI - Creating New VLS Silicon Nanowire Contact Geometries by Controlling Catalyst Migration. AB - The formation of self-assembled contacts between vapor-liquid-solid grown silicon nanowires and flat silicon surfaces was imaged in situ using electron microscopy. By measuring the structural evolution of the contact formation process, we demonstrate how different contact geometries are created by adjusting the balance between silicon deposition and Au migration. We show that electromigration provides an efficient way of controlling the contact. The results point to novel device geometries achieved by direct nanowire growth on devices. PMID- 26367352 TI - Friction mediated by redox-active supramolecular connector molecules. AB - We report on a friction study at the nanometer scale using atomic force microscopy under electrochemical control. Friction arises from the interaction between two surfaces functionalized with cyclodextrin molecules. The interaction is mediated by connector molecules with (ferrocenylmethyl)ammonium end groups forming supramolecular complexes with the cyclodextrin molecules. With ferrocene connector molecules in solution, the friction increases by a factor of up to 12 compared to control experiments without connector molecules. The electrochemical oxidation of ferrocene to ferrocenium causes a decrease in friction owing to the lower stability of ferrocenium-cyclodextrin complex. Upon switching between oxidative and reduction potentials, a change in friction by a factor of 1.2-1.8 is observed. Isothermal titration calorimetry reveals fast dissociation and rebinding kinetics and thus an equilibrium regime for the friction experiments. PMID- 26367353 TI - Commentary on 'Core public health functions for New Zealand'. AB - The special article on 'Core public health functions for New Zealand' by Williams and colleagues in this issue of the Journal is a very valuable contribution to public health thinking in this country. The inter-relationships between goals, outcomes sought, core functions and key principles are all well outlined. The valuable illustrative examples in their Table 2 indicate the depth of experience and thinking by the authors. PMID- 26367354 TI - Winners and losers during the 2011 Rugby World Cup. PMID- 26367355 TI - Trauma training of general surgical trainees in New Zealand. PMID- 26367356 TI - Core Public Health Functions for New Zealand. AB - This special article defines the public health principles and core public health functions that are combined to produce the public health services essential for a highly-functioning New Zealand health system. The five core functions are: health assessment and surveillance; public health capacity development; health promotion; health protection; and preventive interventions. The core functions are interconnected and are rarely delivered individually. Public health services are not static, but evolve in response to changing needs, priorities, evidence and organisational structures. The core functions describe the different ways public health contributes to health outcomes in New Zealand and provide a framework for ensuring services are comprehensive and robust. PMID- 26367357 TI - End-of-life medical decision making in general practice in New Zealand--13 years on. AB - AIMS: The aim of this study was to explore medical decision-making practices at the end-of-life made by GPs (MDEL) in New Zealand and to identify changes in practice with a previous study published in 2004. METHODS: A postal questionnaire was sent to 3,420 GPs in New Zealand in May 2013. Anonymous phone interviews were also undertaken. Analysis of the questionnaire was done on IBM SPSS Statistics 21. RESULTS: There was a 21% response rate from two mail outs. Of the 650 GPs who responded, 547 had contact with a patient prior to death and had the potential to make a MDEL. Of these, 359 (65.6%) reported making a MDEL. Of the 359 GPs who reported making a MDEL, 16 (4.5%) attributed death to a drug that had been prescribed, supplied or administered explicitly for the purpose of hastening the patient's death. The alleged involvement of nurses in practices that intentionally hasten death is high. CONCLUSION: Our study shows that some GPs have explicitly assisted their patients to die, that nurses are allegedly involved, and there is a tendency towards more discussion with patients about MDEL. PMID- 26367358 TI - Multidisciplinary operating room simulation-based team training to reduce treatment errors: a feasibility study in New Zealand hospitals. AB - AIMS: Communication failures in healthcare are frequent and linked to adverse events and treatment errors. Simulation-based team training has been proposed to address this. We aimed to explore the feasibility of a simulation-based course for all members of the operating room (OR) team, and to evaluate its effectiveness. METHODS: Members of experienced OR teams were invited to participate in three simulated clinical events using an integrated surgical and anesthesia model. We collected information on costs, Behavioural Marker of Risk Index (BMRI) (a measure of team information sharing) and participants' educational gains. RESULTS: We successfully recruited 20 full OR teams. Set up costs were NZ$50,000. Running costs per course were NZ$4,000, excluding staff. Most participants rated the course highly. BMRI improved significantly (P = 0.04) and thematic analysis identified educational gains for participants. CONCLUSION: We demonstrated feasibility of multidisciplinary simulation-based training for surgeons, anesthetists, nurses and anaesthetic technicians. The course showed evidence of participant learning and we obtained useful information on cost. There is considerable potential to extend this type of team-based simulation to improve the performance of OR teams and increase safety for surgical patients. PMID- 26367359 TI - Service planning implications of estimating Primary Health Organisation enrolment rate based on a Health Service Utilisation population rather than a Census derived population. AB - AIM: Estimating Primary Health Organisation (PHO) enrolment rates with a census derived estimated resident population denominator may provide misleading results because of numerator and denominator mismatch. This study uses the Health Service Utilisation (HSU) population denominator as an alternative. METHOD: A HSU population was generated by record linkage of routinely collected datasets from the Ministry of Health via encrypted National Health Index (NHI). We compare PHO enrolment rates by age and ethnicity in Counties Manukau District Health Board (CMDHB) in 2013. RESULTS: In CMDHB, 98% of people who had utilised publicly funded health services in 2013 were enrolled in a PHO in 2013. Using the HSU population as a denominator, PHO enrolment rates for Maaori, Pacific, Asian, New Zealand European/Other population groups were 98.3%, 97.7%, 97.6%, and 98.3% respectively. Just under 4% of people discharged from CMDHB inpatient facilities were not enrolled in a PHO within a month from the day of discharge in 2013. CONCLUSION: Using the HSU population as a proxy of health services need, PHO enrolment rates were similar across ethnicities in the CMDHB population. Support to improve PHO enrolment coverage would be more efficient if the HSU population were used to target people who are not yet enrolled in a PHO. PMID- 26367360 TI - Trauma training in New Zealand: A survey of General Surgical trainees. AB - INTRODUCTION: The surgical management of trauma is an important aspect of training in general surgery. The aim of this study is to assess the current levels of experience in trauma management and attitudes towards adequacy of exposure amongst current trainees in New Zealand. METHOD: An anonymous survey assessing experience in trauma management posted to all New Zealand general surgical trainees in Surgical Education and Training (SET) years two to five. RESULTS: 21 of 62 trainees responded. There was little correlation between SET levels or months of registrar experience and number of operations performed, which ranged from 0 to 22. 81% of trainees felt their exposure to trauma operations was inadequate. The average supervision rate for operating was 73%. The majority of trainees showed an interest in trauma with 76% replying yes, with four answering maybe, and one no. 100% of trainees felt that training in trauma was at least somewhat important. DISCUSSION: Experience and training in trauma care is very important but currently inadequate to allow the safe delivery of surgical treatment for injured patients by well-trained surgeons. Surgical training needs to be reorganised, using all available clinical and simulation resources to ensure this critical skills area is maintained for all trainees. PMID- 26367361 TI - New Zealand university students' knowledge and attitudes to organ and tissue donation. AB - AIM: Organ and tissue donation (OTD) rates in New Zealand are low compared to many countries. Young adults are 'tomorrow's donors', yet the attitudes and knowledge of this group to OTD have not been examined locally. Such information is relevant to ODT education and clinical engagement. METHOD: A random sample of University of Otago students (<25 years, permanent New Zealand resident) was surveyed to examine OTD knowledge and attitudes. This included general knowledge, OTD policy (opt-in, opt-out), donation by self, and donation by loved ones. Questions included yes-no, multiple choice, and Likert-type responses. Analyses by sex, demographic characteristics, supportive attitudes to ODT, and University of Otago student profile were performed. RESULTS: 180 responses were gathered (mean age 20.1 years, 67% female, 68% New Zealand European); there were no age or response differences between sexes, participants were generally not representative of the University of Otago student profile. Outcomes indicated limited OTD knowledge, positive support for OTD, and willingness to engage in donation the decision-making process for loved ones. Differences between supportive and non-supportive OTD attitudes was seen for some questions. CONCLUSION: Findings highlight areas for strategic OTD public engagement and provide details relevant to guiding appropriate clinical interaction in facilitating decisions about OTD. PMID- 26367362 TI - Impact of the New Zealand 2011 Rugby World Cup on an urban emergency department. AB - AIMS: The next Rugby World Cup will take place in England commencing August 2015. This paper describes the preparation and workload relating to the previous Rugby World Cup, held in New Zealand 2011, as it affected the primary receiving hospital for the main venue. This paper describes preparation arrangements and actual workload patterns to assist planners with future similar events. METHODS: Preparations for the tournament were summarised, and data gathered from the Auckland City Hospital database were analysed for total and hourly presentation rates, short-stay observation workload, admission rate, 6-hour target compliance and type of presentation. RESULTS: Overall workload during the tournament increased by 8%, but much larger spikes in attendances per hour and short-stay workload related to the major events were experienced. Alcohol-related presentations were very much more prominent than usual. Pre-arranged additional staffing and flow arrangements allowed the department to maintain 6-hour target compliance. CONCLUSION: Major sporting events, such as the Rugby World Cup, require special arrangements to be put in place for the main local receiving Emergency Department, especially around the major events of a tournament. PMID- 26367363 TI - Informed consent to breech birth in New Zealand. AB - The authors note significant room for improvement in facilitating informed consent in the management of breech presentation. New Zealand maternity care providers, including midwives, general practitioners and specialist obstetricians, have legal duties to provide full and unbiased information about risks and benefits of all relevant treatment options. In the case of breech presentation, such options include the interventions of external cephalic version or planned caesarean section, as well as the option to decline intervention and proceed with a planned vaginal breech birth. Information should be presented in a balanced and accessible way and not limited to the provider's personal preferences. Women have legal rights to make an informed choice, to give or refuse consent, to a second opinion and to co-operation among providers. The right of competent persons to refuse medical treatment, including the right to refuse caesarean section, is well established. Clinical policies therefore should include appropriate and non-coercive care for women who choose to birth their breech-presenting baby vaginally, compliance with such policies should be the norm, and consideration should be given to any institutional reforms or educational priorities needed to achieve this. PMID- 26367364 TI - Metastatic melanoma presenting as a testicular lump. PMID- 26367365 TI - An uncommon complication of post trans-sphenoidal surgery for pituitary adenoma. PMID- 26367366 TI - Physician assisted dying--a survey of Waikato General Practitioners. PMID- 26367367 TI - The economic burden of colorectal cancer in New Zealand. PMID- 26367368 TI - Appropriate Use Criteria Require Data. PMID- 26367369 TI - Thermoelectric properties of single-layered SnSe sheet. AB - Motivated by the recent study of inspiring thermoelectric properties in bulk SnSe [Zhao et al., Nature, 2014, 508, 373] and the experimental synthesis of SnSe sheets [Chen et al., J. Am. Chem. Soc., 2013, 135, 1213], we have carried out systematic calculations for a single-layered SnSe sheet focusing on its stability, electronic structure and thermoelectric properties by using density functional theory combined with Boltzmann transport theory. We have found that the sheet is dynamically and thermally stable with a band gap of 1.28 eV, and the figure of merit (ZT) reaches 3.27 (2.76) along the armchair (zigzag) direction with optimal n-type carrier concentration, which is enhanced nearly 7 times compared to its bulk counterpart at 700 K due to quantum confinement effect. Furthermore, we designed four types of thermoelectric couples by assembling single-layered SnSe sheets with different transport directions and doping types, and found that their efficiencies are all above 13%, which are higher than those of thermoelectric couples made of commercial bulk Bi2Te3 (7%-8%), suggesting the great potential of single-layered SnSe sheets for heat-electricity conversion. PMID- 26367370 TI - Chimerical anterolateral thigh flap for plantar reconstruction. AB - OBJECTIVE: The purpose of this study is to evaluate the results of reconstruction and rehabilitation of patients with plantar defects by using a chimerical flap of muscle and skin from anterolateral thigh. METHODS: Twenty-five patients with plantar defects were reconstructed with a chimerical anterolateral thigh (ALT) flap, composed by a vastus lateralis muscle segment and a thinned skin island. Neurorrhaphy between lateral femoral cutaneous nerve and calcaneal nerve was performed in 7 patients. Evaluation of flap contour and stability and patient ambulation was performed 6 and 12 months after surgery. Evaluation of cutaneous sensiblity of ALT flap and contralateral thigh was performed 12 months after surgery using Pressure Specified Sensory DeviceTM (PSSDTM). RESULTS: Flap viability was complete in 23 patients and 2 patients had complications with partial flap loss of its cutaneous component. Six months postoperatively, flap contour, and stability was considered good in 19 and 21 patients respectively, and all 25 patients presented good ambulation. Twelve months postoperatively, all 25 patients presented good flap contour and stability, as well as good ambulation. All 7 flaps undergoing to reinnervation partially recovered cutaneous sensibility in comparison to donor site (contralateral thigh). Cutaneous tactile thresholds (g/mm(2) ) of static one-point test and moving one-point test from the ALT flap and the contralateral thigh presented statistically significant differences, for both comparisons (P = 0.009, P = 0.002). CONCLUSION: This flap is suitable for reconstruction of plantar defects, with good flap contour and stability, proper patient ambulation and low complication rates. PMID- 26367371 TI - Critical Evaluation of Current Concepts and Moving to New Horizons in the Management of IBD. PMID- 26367373 TI - Management of IBD Patients with Current Immunosuppressive Therapy and Concurrent Infections. AB - In an era of increasing use of immunomodulator therapy and biologics, opportunistic infections (OI) have emerged as a pivotal safety issue in patients with inflammatory bowel disease (IBD). Clinical studies, registries and case reports warn about the increased risk for infections, particularly OIs. Today, the challenge for a physician is not only to manage IBD, but also to recognize, prevent and treat common and uncommon infections. The 2014 European Crohn's and Colitis Organisation (ECCO) guidelines on the management and prevention of OIs in patients with IBD provide clinicians with guidance on the prevention, detection and management of OIs. Proposals may appear radical, potentially changing the current practice, but we believe that the recommendations will help optimize patient outcomes by reducing the morbidity and mortality related to OIs. In this ongoing process, prevention is by far the first and most important step. Prevention of OIs relies on recognition of risk factors for infection, the use of primary or secondary chemoprophylaxis, careful monitoring (clinical and laboratory work-up) before and during the use of immunomodulators, vaccination and education of the patient. Special recommendations should also be given to patients before and after travel. PMID- 26367375 TI - Morphological Changes of Human Corneal Endothelial Cells after Rho-Associated Kinase Inhibitor Eye Drop (Ripasudil) Administration: A Prospective Open-Label Clinical Study. AB - PURPOSE: To investigate the effect and safety of a selective Rho kinase inhibitor, ripasudil 0.4% eye drops, on corneal endothelial cells of healthy subjects. DESIGN: Prospective, interventional case series. METHODS: In this study, 6 healthy subjects were administered ripasudil 0.4% in the right eye twice daily for 1 week. Morphological changes and corneal endothelial cell density were examined by noncontact and contact specular microscopy. Central corneal thickness and corneal volume of 5 mm-diameter area of center cornea were analyzed by Pentacam Scheimpflug topography. All the above measurements were conducted in both eyes before administration, 1.5 and 6 hours after the initial administration on day 0; and in the same manner after the final administration on day 7. RESULTS: By noncontact specular microscopy, indistinct cell borders with pseudo guttae were observed, but by contact specular microscopy, morphological changes of corneal endothelial cells were mild and pseudo guttae was not observed after single and repeated administration of ripasudil in all subjects. These changes resolved prior to the next administration, and corneal endothelial cell density, central corneal thickness and corneal volume were not changed throughout the study period. CONCLUSION: Transient morphological changes of corneal endothelial cells such as indistinct cell borders with pseudo guttae were observed by noncontact specular microscopy in healthy subjects after ripasudil administration. Corneal edema was not observed and corneal endothelial cell density did not decrease after 1 week repetitive administration. These morphological changes were reversible and corneal endothelial cell morphology returned to normal prior to the next administration. TRIAL REGISTRATION: JAPIC Clinical Trials Information 142705. PMID- 26367374 TI - Intracellular Cytokine Staining and Flow Cytometry: Considerations for Application in Clinical Trials of Novel Tuberculosis Vaccines. AB - Intracellular cytokine staining combined with flow cytometry is one of a number of assays designed to assess T-cell immune responses. It has the specific advantage of enabling the simultaneous assessment of multiple phenotypic, differentiation and functional parameters pertaining to responding T-cells, most notably, the expression of multiple effector cytokines. These attributes make the technique particularly suitable for the assessment of T-cell immune responses induced by novel tuberculosis vaccines in clinical trials. However, depending upon the particular nature of a given vaccine and trial setting, there are approaches that may be taken at different stages of the assay that are more suitable than other alternatives. In this paper, the Tuberculosis Vaccine Initiative (TBVI) TB Biomarker Working group reports on efforts to assess the conditions that will determine when particular assay approaches should be employed. We have found that choices relating to the use of fresh whole blood or peripheral blood mononuclear cells (PBMC) and frozen PBMC; use of serum containing or serum-free medium; length of stimulation period and use of co stimulatory antibodies can all affect the sensitivity of intracellular cytokine assays. In the case of sample material, frozen PBMC, despite some loss of sensitivity, may be more advantageous for batch analysis. We also recommend that for multi-site studies, common antibody panels, gating strategies and analysis approaches should be employed for better comparability. PMID- 26367376 TI - Identification of melatonin in Trichoderma spp. and detection of melatonin content under controlled-stress growth conditions from T. asperellum. AB - T. koningii, T. harzianum, T. asperellum, T. longibrachiatum, and T. viride were analyzed using liquid chromatography-tandem mass spectrometry to determine whether melatonin is present. Results showed that there were abundant amounts of endogenous melatonin in five Trichoderma species, but no melatonin was found in any of the culture filtrates. T. asperellum had the highest amount of melatonin (27.588 +/- 0.326 MUg g(-1) dry mass), followed by T. koningii, T. harzianum, T. longibrachiatum, and T. viride. The endogenous melatonin content of T. asperellum in controlled-stress growth conditions was also detected. The data showed that chemical stressors (CdCl2 , CuSO4 , and H2 O2 ) provoked an increase in endogenous melatonin levels. CdCl2 had the highest stimulatory effect on melatonin production, as the product reached reaching up to three times the melatonin content of the control. NaCl stimulated a decrease of melatonin. Acidic conditions (pH 3 and pH 5) as well as slightly alkaline conditions (pH 9) resulted in an increase in the melatonin content, whereas pH11 resulted in a significant decrease in the melatonin content, only 12.276 +/- 0.205 MUg g(-1) dry mass. The current study is first to report melatonin content and the change of melatonin content under different stress situations in Trichoderma spp. PMID- 26367377 TI - Effect of Acetazolamide on Obesity-Induced Glomerular Hyperfiltration: A Randomized Controlled Trial. AB - AIMS: Obesity is an important risk factor for the development of chronic kidney disease. One of the major factors involved in the pathogenesis of obesity associated kidney disease is glomerular hyperfiltration. Increasing salt-delivery to the macula densa is expected to decrease glomerular filtration rate (GFR) by activating tubuloglomerular feedback. Acetazolamide, a carbonic anhydrase inhibitor which inhibits salt reabsorption in the proximal tubule, increases distal salt delivery. Its effects on obesity-related glomerular hyperfiltration have not previously been studied. The aim of this investigation was to evaluate whether administration of acetazolamide to obese non diabetic subjects reduces glomerular hyperfiltration. MATERIALS AND METHODS: The study was performed using a randomized double-blind crossover design. Obese non-diabetic men with glomerular hyperfiltration were randomized to receive intravenously either acetazolamide or furosemide at equipotent doses. Twelve subjects received the allocated medications. Two weeks later, the same subjects received the drug which they had not received during the first study. Inulin clearance, p-aminohippuric acid clearance and fractional lithium excretion were measured before and after medications administration. The primary end point was a decrease in GFR, measured as inulin clearance. RESULTS: GFR decreased by 21% following acetazolamide and did not decrease following furosemide. Renal vascular resistance increased by 12% following acetazolamide, while it remained unchanged following furosemide administration. Natriuresis increased similarly following acetazolamide and furosemide administration. Sodium balance was similar in both groups. CONCLUSIONS: Intravenous acetazolamide decreased GFR in obese non-diabetic men with glomerular hyperfiltration. Furosemide, administered at equipotent dose, did not affect GFR, suggesting that acetazolamide reduced glomerular hyperfiltration by activating tubuloglomerular feedback. TRIAL REGISTRATION: ClinicalTrials.gov NCT01146288. PMID- 26367378 TI - ERBB3 Positively Correlates with Intestinal Stem Cell Markers but Marks a Distinct Non Proliferative Cell Population in Colorectal Cancer. AB - Several studies have suggested ERBB3/HER3 may be a useful prognostic marker for colorectal cancer. Tumours with an intestinal stem cell signature have also been shown to be more aggressive. Here, we investigate whether ERBB3 is associated with intestinal stem cell markers in colorectal cancer and if cancer stem cells within tumours are marked by expression of ERBB3. Expression of ERBB3 and intestinal stem cell markers (LGR5, EPHB2, CD44s and CD44v6) was assessed by qRT PCR in primary colorectal tumours (stages 0 to IV) and matched normal tissues from 53 patients. The localisation of ERBB3, EPHB2 and KI-67 within tumours was investigated using co-immunofluorescence. Expression of ERBB3 and intestinal stem cell markers were significantly elevated in adenomas and colorectal tumours compared to normal tissue. Positive correlations were found between ERBB3 and intestinal stem cell markers. However, co-immunofluorescence analysis showed that ERBB3 and EPHB2 marked specific cell populations that were mutually exclusive within tumours with distinct proliferative potentials, the majority of ERBB3+ve cells being non-proliferative. This pattern resembles cellular organisation within normal colonic epithelium where EPHB2 labelled proliferative cells reside at the crypt base and ERBB3+ve cells mark differentiated cells at the top of crypts. Our results show that ERBB3 and intestinal stem cell markers correlate in colorectal cancers. ERBB3 localises to differentiated cell populations within tumours that are non-proliferative and distinct from cancer stem cells. These data support the concept that tumours contain discrete stem, proliferative and differentiation compartments similar to that present in normal crypts. PMID- 26367379 TI - Host Cell Proteins: The Hidden Side of Biosimilarity Assessment. AB - One major concern with biosimilars is that small differences compared with reference products might lead to unforeseen immunogenicity, thus affecting patient safety and drug efficacy. Differences could be due to either post translational modifications of the therapeutic protein and/or to traces of impurities from the manufacturing process. The results presented in this communication illustrate the efforts to assess "biosimilarity" of a biosimilar candidate to a reference product for a specific group of process-related impurities, the host cell proteins (HCP). Extensive characterization of HCP in the drug substance of a biosimilar candidate revealed the identity of HCP copurifying with the protein of interest and guided process development to improve overall HCP clearance in the downstream process. The data presented illustrate the challenge of matching the reference product on either quantitative or qualitative aspects of HCP impurities. PMID- 26367381 TI - Maturation of 6S regulatory RNA to a highly elongated structure. AB - As bacterial populations leave the exponential growth phase and enter the stationary phase, their patterns of gene expression undergo marked changes. A key effector of this change is 6S RNA, which is a highly conserved regulatory RNA that impedes the transcription of genes associated with exponential growth by forming an inactivating ternary complex with RNA polymerase and sigma factor sigma(70) (sigma(70)-RNAP). In Escherichia coli, the endoribonuclease RNase E generates 6S RNA by specific cleavage of a precursor that is nearly twice the size of the 58 kDa mature form. We have explored recognition of the precursor by RNase E, and observed that processing is inhibited under conditions of excess substrate. This finding supports a largely distributive mechanism, meaning that each round of catalysis results in enzyme dissociation and re-binding to the substrate. We show that the precursor molecule and the mature 6S share a structural core dominated by an A-type helix, indicating that processing is not accompanied by extensive refolding. Both precursor and mature forms of 6S have a highly stable secondary structure, adopt an elongated shape, and show the potential to form dimers under specific conditions; nonetheless, 6S has a high structural plasticity that probably enables it to be structurally adapted upon binding to its cognate protein partners. Analysis of the 6S-sigma(70)-RNAP complex by native mass spectrometry reveals a stable association with a stoichiometry of 1:1:1. A theoretical 3D model of mature 6S is presented, which is consistent with the experimental data and supports a previously proposed structure with a small stem-loop inside the central bubble. PMID- 26367380 TI - Do the Levels of Maternal Plasma Trace Elements Affect Fetal Nuchal Translucency Thickness? AB - OBJECTIVE: Fetal nuchal translucency (NT) thickness is an important marker for prenatal screening; however, studies focusing on the correlation between maternal trace element levels and NT thickness are limited. The aim of this study was to evaluate maternal trace element levels during the first trimester and to investigate the association between maternal trace element levels and fetal NT thickness. METHODS: In total, 113 samples were obtained from singleton pregnant women. Maternal plasma samples were collected in the first trimester of gestation. Plasma trace element levels were measured using Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Nuchal translucency thickness was measured using ultrasonography at 10-14 weeks of gestation. RESULTS: We found that maternal plasma potassium (K) levels had a significant negative correlation with both NT (r = -0.230, p < 0.05) and NT Multiples of the Median (NT MoM) (r = 0.206, p < 0.05). After adjustment for potential confounders, log-transformed maternal plasma potassium levels in the first trimester were significantly associated with fetal NT (NT MoM: beta = -0.68, p < 0.05; NT: beta = -1.20, p < 0.01). Although not statistically significant, the As, Hg and Pb levels in maternal plasma were positively correlated with NT, and the Mg, Cu, Zn, Na and Ca levels were negatively correlated with NT. CONCLUSION: Maternal plasma K levels during the first trimester appeared to be associated with NT thickness. The essential elements tended to decrease NT thickness, and non-essential elements tended to increase it. PMID- 26367382 TI - A Computationally Inexpensive Optimal Guidance via Radial-Basis-Function Neural Network for Autonomous Soft Landing on Asteroids. AB - Optimal guidance is essential for the soft landing task. However, due to its high computational complexities, it is hardly applied to the autonomous guidance. In this paper, a computationally inexpensive optimal guidance algorithm based on the radial basis function neural network (RBFNN) is proposed. The optimization problem of the trajectory for soft landing on asteroids is formulated and transformed into a two-point boundary value problem (TPBVP). Combining the database of initial states with the relative initial co-states, an RBFNN is trained offline. The optimal trajectory of the soft landing is determined rapidly by applying the trained network in the online guidance. The Monte Carlo simulations of soft landing on the Eros433 are performed to demonstrate the effectiveness of the proposed guidance algorithm. PMID- 26367383 TI - Nonbiological factors affecting survival in younger patients with acute myeloid leukemia. AB - BACKGROUND: Progress has been made in determining the biological variants of acute myelogenous leukemia (AML) and their prognostic implications. However, to the authors' knowledge, little is known regarding the impact of nonbiological factors (NBFs) on the survival of patients with AML. METHODS: The impact of NBFs (marital status, insurance status, county-level income, and education) on survival was assessed along with biological factors (disease subtype, sex, age, and race/ethnicity) using a cohort of patients aged 19 to 64 years who were diagnosed with AML between 2007 and 2011 and reported to the Surveillance, Epidemiology, and End Results program registry (SEER 18). RESULTS: There were 5541 patients included. The median overall survival for the entire study population was 16 months. On multivariate analysis, an increased risk of death was independently linked to being a Medicaid beneficiary, uninsured, single, divorced, and residing in a county within the lower 3 quintiles of median household income. NBFs affected the risk of early (<2 months) and late mortality and their impact was confirmed among patients known to have received chemotherapy. CONCLUSIONS: Insurance status, marital status, and county-level income were found to independently affect the survival of younger patients with AML and should be integrated into outcome comparisons. Interventions are needed to mitigate the impact of social factors on survival among patients with AML. PMID- 26367384 TI - Selfies of Imperial Cormorants (Phalacrocorax atriceps): What Is Happening Underwater? AB - During the last few years, the development of animal-borne still cameras and video recorders has enabled researchers to observe what a wild animal sees in the field. In the present study, we deployed miniaturized video recorders to investigate the underwater foraging behavior of Imperial cormorants (Phalacrocorax atriceps). Video footage was obtained from 12 animals and 49 dives comprising a total of 8.1 h of foraging data. Video information revealed that Imperial cormorants are almost exclusively benthic feeders. While foraging along the seafloor, animals did not necessarily keep their body horizontal but inclined it downwards. The head of the instrumented animal was always visible in the videos and in the majority of the dives it was moved constantly forward and backward by extending and contracting the neck while travelling on the seafloor. Animals detected prey at very short distances, performed quick capture attempts and spent the majority of their time on the seafloor searching for prey. Cormorants foraged at three different sea bottom habitats and the way in which they searched for food differed between habitats. Dives were frequently performed under low luminosity levels suggesting that cormorants would locate prey with other sensory systems in addition to sight. Our video data support the idea that Imperial cormorants' efficient hunting involves the use of specialized foraging techniques to compensate for their poor underwater vision. PMID- 26367385 TI - Progress in the management of retrorectal tumours. AB - AIM: Tumours in the retrorectal space are rare and pathologically heterogeneous. The roles of imaging and preoperative biopsy, nonoperative management and the indications for surgical resection are controversial. This study investigated a series of retrorectal tumours treated in a single institution with the aim of producing a modern improved management algorithm. METHOD: A retrospective analysis was conducted of the management of all retrorectal lesions identified between 1998 and 2013 from a radiology database search. Patient demographics, presenting symptoms, imaging, biopsy, management and the results were recorded. Descriptive statistics were used and Kaplan-Meier survival analysis was performed. RESULTS: Sixty-nine patients with a confirmed retrorectal tumour were identified. The median age was 50 (36-67 interquartile range) and 42 (56%) were female. Twenty (29%) of the tumours were malignant: 4 of 41 cystic lesions were malignant (12.9%) vs. 16 of 28 solid (or heterogeneous) lesions (57.1%) (P < 0.0001). Imaging demonstrated a 95% sensitivity and 64% specificity for differentiating benign from malignant tumours. Magnetic resonance imaging (MRI) was significantly better at distinguishing between benign and malignant tumours than computed tomography (94% vs. 64%, P = 0.03). Percutaneous biopsy was performed in 16 patients and only 27 underwent resection. There was no evidence of local recurrence associated with biopsy. Solid lesions were associated with a nonsignificant decreased overall survival (P = 0.348). CONCLUSION: This study demonstrated that MRI should be the investigation of choice for retrorectal lesions. Biopsy of solid lesions is safe and useful for guiding neoadjuvant and surgical therapy. Cystic lesions without suspicious radiological features can be followed by serial imaging without resection. PMID- 26367387 TI - Transcriptomic Profiling of Spleen in Grass-Fed and Grain-Fed Angus Cattle. AB - The grass-fed cattle obtain nutrients directly from pastures containing limited assimilable energy but abundant amount of fiber; by contrast, grain-fed steers receive a diet that is comprised mainly of grains and serves as an efficient source of high-digestible energy. Besides energy, these two types of diet differ in a large number of nutritional components. Additionally, animals maintained on rich-energy regimen are more likely to develop metabolic disorders and infectious diseases than pasture raised individuals. Thus, we hypothesize that spleen-a relevant immune organ-may function differently under disparate regimes. The objective of this study was to find the differentially expressed genes in the spleen of grass-fed and grain-fed steers, and furtherly explore the potential involved biopathways. Through RNA sequencing (RNA-Seq), we detected 123 differentially expressed genes. Based on these genes, we performed an Ingenuity Pathway Analysis (IPA) and identified 9 significant molecular networks and 13 enriched biological pathways. Two of the pathways, Nur77 signaling in T lymphocytes and calcium-induced T lymphocyte apoptosis which are immune related, contain a pair of genes HLA-DRA and NR4A1 with dramatically altered expression level. Collectively, our results provided valuable insights into understanding the molecular mechanism of spleen under varied feeding regimens. PMID- 26367386 TI - Modeling the Regulatory Mechanisms by Which NLRX1 Modulates Innate Immune Responses to Helicobacter pylori Infection. AB - Helicobacter pylori colonizes half of the world's population as the dominant member of the gastric microbiota resulting in a lifelong chronic infection. Host responses toward the bacterium can result in asymptomatic, pathogenic or even favorable health outcomes; however, mechanisms underlying the dual role of H. pylori as a commensal versus pathogenic organism are not well characterized. Recent evidence suggests mononuclear phagocytes are largely involved in shaping dominant immunity during infection mediating the balance between host tolerance and succumbing to overt disease. We combined computational modeling, bioinformatics and experimental validation in order to investigate interactions between macrophages and intracellular H. pylori. Global transcriptomic analysis on bone marrow-derived macrophages (BMDM) in a gentamycin protection assay at six time points unveiled the presence of three sequential host response waves: an early transient regulatory gene module followed by sustained and late effector responses. Kinetic behaviors of pattern recognition receptors (PRRs) are linked to differential expression of spatiotemporal response waves and function to induce effector immunity through extracellular and intracellular detection of H. pylori. We report that bacterial interaction with the host intracellular environment caused significant suppression of regulatory NLRC3 and NLRX1 in a pattern inverse to early regulatory responses. To further delineate complex immune responses and pathway crosstalk between effector and regulatory PRRs, we built a computational model calibrated using time-series RNAseq data. Our validated computational hypotheses are that: 1) NLRX1 expression regulates bacterial burden in macrophages; and 2) early host response cytokines down regulate NLRX1 expression through a negative feedback circuit. This paper applies modeling approaches to characterize the regulatory role of NLRX1 in mechanisms of host tolerance employed by macrophages to respond to and/or to co-exist with intracellular H. pylori. PMID- 26367388 TI - Evaluating the Impact of Computerized Provider Order Entry on Medical Students Training at Bedside: A Randomized Controlled Trial. AB - OBJECTIVE: To evaluate the impact of computerized provider order entry (CPOE) at the bedside on medical students training. MATERIALS AND METHODS: We conducted a randomized cross-controlled educational trial on medical students during two clerkship rotations in three departments, assessing the impact of the use of CPOE on their ability to place adequate monitoring and therapeutic orders using a written test before and after each rotation. Students' satisfaction with their practice and the order placement system was surveyed. A multivariate mixed model was used to take individual students and chief resident (CR) effects into account. Factorial analysis was applied on the satisfaction questionnaire to identify dimensions, and scores were compared on these dimensions. RESULTS: Thirty-six students show no better progress (beginning and final test means = 69.87 and 80.98 points out of 176 for the control group, 64.60 and 78.11 for the CPOE group, p = 0.556) during their rotation in either group, even after adjusting for each student and CR, but show a better satisfaction with patient care and greater involvement in the medical team in the CPOE group (p = 0.035*). Both groups have a favorable opinion regarding CPOE as an educational tool, especially because of the order reviewing by the supervisor. CONCLUSION: This is the first randomized controlled trial assessing the performance of CPOE in both the progress in prescriptions ability and satisfaction of the students. The absence of effect on the medical skills must be weighted by the small time scale and low sample size. However, students are more satisfied when using CPOE rather than usual training. PMID- 26367389 TI - Beta-lactam versus beta- lactam/macrolide therapy in pediatric outpatient pneumonia. AB - OBJECTIVE: The objective was to evaluate the comparative effectiveness of beta lactam monotherapy and beta- lactam/macrolide combination therapy in the outpatient management of children with community-acquired pneumonia (CAP). METHODS: This retrospective cohort study included children, ages 1-18 years, with CAP diagnosed between January 1, 2008 and January 31, 2010 during outpatient management in the Geisinger Health System. The primary exposure was receipt of beta-lactam monotherapy or beta-lactam/macrolide combination therapy. The primary outcome was treatment failure, defined as a follow-up visit within 14 days of diagnosis resulting in a change in antibiotic therapy. Logistic regression within a propensity score- restricted cohort was used to estimate the likelihood of treatment failure. RESULTS: Of 717 children in the analytical cohort, 570 (79.4%) received beta-lactam monotherapy and 147 (20.1%) received combination therapy. Of those who received combination therapy 58.2% of children were under 6 years of age. Treatment failure occurred in 55 (7.7%) children, including in 8.1% of monotherapy recipients, and 6.1% of combination therapy recipients. Treatment failure rates were highest in children 6-18 years receiving monotherapy (12.9%) and lowest in children 6-18 years receiving combination therapy (4.0%). Children 6-18 years of age who received combination therapy were less likely to fail treatment than those who received beta-lactam monotherapy (propensity-adjusted odds ratio, 0.51; 95% confidence interval, 0.28, 0.95). CONCLUSION: Children 6-18 years of age who received beta- lactam/macrolide combination therapy for CAP in the outpatient setting had lower odds of treatment failure compared with those who received beta-lactam monotherapy. PMID- 26367390 TI - Single-Step Exfoliation and Covalent Functionalization of MoS2 Nanosheets by an Organosulfur Reaction. AB - A simple approach to exfoliate and functionalize MoS2 in a single-step is described, which combines the dispersion of MoS2 in polybutadiene solution and ultrasonication processes. The great advantage of this process is that a colloidal stability of MoS2 in nonpolar solvent is achieved by chemically bonding polybutadiene on the perimeter edge sites of MoS2 sheets. In addition, elastomeric nanocomposite has been prepared with singular mechanical properties using functionalized MoS2 as nanofiller in a polybutadiene matrix with a subsequent vulcanization reaction. PMID- 26367391 TI - Phenylalanine and Phenylglycine Analogues as Arginine Mimetics in Dengue Protease Inhibitors. AB - Dengue virus is an increasingly global pathogen. One of the promising targets for antiviral drug discovery against dengue and related flaviviruses such as West Nile virus is the viral serine protease NS2B-NS3. We here report the synthesis and in vitro characterization of potent peptidic inhibitors of dengue virus protease that incorporate phenylalanine and phenylglycine derivatives as arginine mimicking groups with modulated basicity. The most promising compounds were (4 amidino)-L-phenylalanine-containing inhibitors, which reached nanomolar affinities against dengue virus protease. The type and position of the substituents on the phenylglycine and phenylalanine side chains has a significant effect on the inhibitory activity against dengue virus protease and selectivity against other proteases. In addition, the non-natural, basic amino acids described here may have relevance for the development of other peptidic and peptidomimetic drugs such as inhibitors of the blood clotting cascade. PMID- 26367392 TI - Drosophila Eye Model to Study Neuroprotective Role of CREB Binding Protein (CBP) in Alzheimer's Disease. AB - BACKGROUND: The progressive neurodegenerative disorder Alzheimer's disease (AD) manifests as loss of cognitive functions, and finally leads to death of the affected individual. AD may result from accumulation of amyloid plaques. These amyloid plaques comprising of amyloid-beta 42 (Abeta42) polypeptides results from the improper cleavage of amyloid precursor protein (APP) in the brain. The Abeta42 plaques have been shown to disrupt the normal cellular processes and thereby trigger abnormal signaling which results in the death of neurons. However, the molecular-genetic mechanism(s) responsible for Abeta42 mediated neurodegeneration is yet to be fully understood. METHODOLOGY/PRINCIPAL FINDINGS: We have utilized Gal4/UAS system to develop a transgenic fruit fly model for Abeta42 mediated neurodegeneration. Targeted misexpression of human Abeta42 in the differentiating photoreceptor neurons of the developing eye of transgenic fly triggers neurodegeneration. This progressive neurodegenerative phenotype resembles Alzheimer's like neuropathology. We identified a histone acetylase, CREB Binding Protein (CBP), as a genetic modifier of Abeta42 mediated neurodegeneration. Targeted misexpression of CBP along with Abeta42 in the differentiating retina can significantly rescue neurodegeneration. We found that gain-of-function of CBP rescues Abeta42 mediated neurodegeneration by blocking cell death. Misexpression of Abeta42 affects the targeting of axons from retina to the brain but misexpression of full length CBP along with Abeta42 can restore this defect. The CBP protein has multiple domains and is known to interact with many different proteins. Our structure function analysis using truncated constructs lacking one or more domains of CBP protein, in transgenic flies revealed that Bromo, HAT and polyglutamine (BHQ) domains together are required for the neuroprotective function of CBP. This BHQ domain of CBP has not been attributed to promote survival in any other neurodegenerative disorders. CONCLUSIONS/SIGNIFICANCE: We have identified CBP as a genetic modifier of Abeta42 mediated neurodegeneration. Furthermore, we have identified BHQ domain of CBP is responsible for its neuroprotective function. These studies may have significant bearing on our understanding of genetic basis of AD. PMID- 26367393 TI - Apoptosis-Promoting Effects of Hematoporphyrin Monomethyl Ether-Sonodynamic Therapy (HMME-SDT) on Endometrial Cancer. AB - OBJECTIVE: The aim of the present study was to examine the apoptosis-promoting effects and mechanisms of hematoporphyrin monomethyl ether (HMME)-sonodynamic therapy (SDT) on endometrial cancer cells in vitro. METHODS: Endometrial cancer cell samples were divided into four groups: 1) untreated control group, 2) HMME group, 3) pure ultrasound group, and 4) HMME combined with ultrasound, i.e. SDT group. CCK-8 method was utilized to assess the inhibiting effect of SDT on the proliferation of endometrial cancer cells. Optical microscope and field emission transmission electron microscopy were used to characterize the morphology changes of the cancer cells induced by the treatments. Apoptosis rate, reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were examined by flow cytometer. Fluorescence intensity measured by laser scanning confocal microscopy was used to explore the variation of intracellular calcium ion (Ca2+) concentration. Apoptosis-related proteins involved in both intrinsic and extrinsic apoptosis signallings were analyzed by western blot. RESULTS: SDT can effectively induce the apoptosis of endometrial cancer cells. Compared with ultrasound which is known as an effective anti-tumor method, SDT leads to a significant improvement on suppression of cell viability and induction of apoptosis, together with more remarkable modifications on the morphology and substructure in both ultrasound sensitive and resistant endometrial cancer cells. Further studies reveals that SDT promotes ROS production, induces loss of MMP and increases intracellular Ca2+ concentration more efficiently than HMME or ultrasound alone. SDT groups also show a rather high expression of apoptosis promoting proteins, including Bax, Fas and Fas-L, and a significant low expression of apoptosis-suspending proteins including Bcl-2 and Survivin. Meanwhile, both cleaved caspse-3 and caspase-8 are dramatically enhanced in SDT groups. Multiple pathways has been proposed in the process, including the intrinsic activation by excessive ROS and overloaded Ca2+, silencing survivin gene, and the extrinsic pathway mediated by the death receptor. CONCLUSION: Given its considerable effectivity in both ultrasound sensitive and resistant cells, SDT may therefore be a promising therapeutic method for treating endometrial cancers. PMID- 26367395 TI - Transcriptome Analysis Reveals Key Flavonoid 3'-Hydroxylase and Flavonoid 3',5' Hydroxylase Genes in Affecting the Ratio of Dihydroxylated to Trihydroxylated Catechins in Camellia sinensis. AB - The ratio of dihydroxylated to trihydroxylated catechins (RDTC) is an important indicator of tea quality and biochemical marker for the study of genetic diversity. It is reported to be under genetic control but the underlying mechanism is not well understood. Flavonoid 3'-hydroxylase (F3'H) and flavonoid 3',5'-hydroxylase (F3'5'H) are key enzymes involved in the formation of dihydroxylated and trihydroxylated catechins. The transcriptome and HPLC analysis of tea samples from Longjing43 and Zhonghuang2 under control and shading treatment were performed to assess the F3'H and F3'5'H genes that might affect RDTC. A total of 74.7 million reads of mRNA seq (2*101bp) data were generated. After de novo assembly, 109,909 unigenes were obtained, and 39,982 of them were annotated using 7 public databases. Four key F3'H and F3'5'H genes (including CsF3'5'H1, CsF3'H1, CsF3'H2 and CsF3'H3) were identified to be closely correlated with RDTC. Shading treatment had little effect on RDTC, which was attributed to the stable expression of these key F3'H and F3'5'H genes. The correlation of the coexpression of four key genes and RDTC was further confirmed among 13 tea varieties by real time PCR and HPLC analysis. The coexpression of three F3'H genes and a F3'5'H gene may play a key role in affecting RDTC in Camellia sinensis. The current results may establish valuable foundation for further research about the mechanism controlling catechin composition in tea. PMID- 26367396 TI - Biotic homogenization of three insect groups due to urbanization. AB - Cities are growing rapidly, thereby expected to cause a large-scale global biotic homogenization. Evidence for the homogenization hypothesis is mostly derived from plants and birds, whereas arthropods have so far been neglected. Here, I tested the homogenization hypothesis with three insect indicator groups, namely true bugs, leafhoppers, and beetles. In particular, I was interested whether insect species community composition differs between urban and rural areas, whether they are more similar between cities than between rural areas, and whether the found pattern is explained by true species turnover, species diversity gradients and geographic distance, by non-native or specialist species, respectively. I analyzed insect species communities sampled on birch trees in a total of six Swiss cities and six rural areas nearby. In all indicator groups, urban and rural community composition was significantly dissimilar due to native species turnover. Further, for bug and leafhopper communities, I found evidence for large scale homogenization due to urbanization, which was driven by reduced species turnover of specialist species in cities. Species turnover of beetle communities was similar between cities and rural areas. Interestingly, when specialist species of beetles were excluded from the analyses, cities were more dissimilar than rural areas, suggesting biotic differentiation of beetle communities in cities. Non-native species did not affect species turnover of the insect groups. However, given non-native arthropod species are increasing rapidly, their homogenizing effect might be detected more often in future. Overall, the results show that urbanization has a negative large-scale impact on the diversity specialist species of the investigated insect groups. Specific measures in cities targeted at increasing the persistence of specialist species typical for the respective biogeographic region could help to stop the loss of biodiversity. PMID- 26367394 TI - Neisseria meningitidis Type IV Pili Composed of Sequence Invariable Pilins Are Masked by Multisite Glycosylation. AB - The ability of pathogens to cause disease depends on their aptitude to escape the immune system. Type IV pili are extracellular filamentous virulence factors composed of pilin monomers and frequently expressed by bacterial pathogens. As such they are major targets for the host immune system. In the human pathogen Neisseria meningitidis, strains expressing class I pilins contain a genetic recombination system that promotes variation of the pilin sequence and is thought to aid immune escape. However, numerous hypervirulent clinical isolates express class II pilins that lack this property. This raises the question of how they evade immunity targeting type IV pili. As glycosylation is a possible source of antigenic variation it was investigated using top-down mass spectrometry to provide the highest molecular precision on the modified proteins. Unlike class I pilins that carry a single glycan, we found that class II pilins display up to 5 glycosylation sites per monomer on the pilus surface. Swapping of pilin class and genetic background shows that the pilin primary structure determines multisite glycosylation while the genetic background determines the nature of the glycans. Absence of glycosylation in class II pilins affects pilus biogenesis or enhances pilus-dependent aggregation in a strain specific fashion highlighting the extensive functional impact of multisite glycosylation. Finally, molecular modeling shows that glycans cover the surface of class II pilins and strongly decrease antibody access to the polypeptide chain. This strongly supports a model where strains expressing class II pilins evade the immune system by changing their sugar structure rather than pilin primary structure. Overall these results show that sequence invariable class II pilins are cloaked in glycans with extensive functional and immunological consequences. PMID- 26367397 TI - [A comparative analysis of effectiveness, tolerance and cost of second generation antidepressants in France]. AB - While French authorities point to the need for rational prescribing, especially concerning psychotropic drugs, few data on the prescription of second-generation antidepressants (SGA) are synthesized for clinicians' use. Our objective is to carry out a comparative analysis of effectiveness and tolerability / acceptability of SGA. Considering the benefit/risk ratio and the cost (generic), the first-line treatment for a major depressive episode may be currently sertraline (50 mg / d). It may however have more digestive side effects than other SSRIs (due to the serotonin action), which calls for caution while increasing doses. Fluoxetine seems relevant in treatment of negative symptoms of schizophrenia (20mg / d) and in bulimia (60mg / d). Fluvoxamine seems relevant in the case of sexual side effects with a previous SSRI, in treatment of anxiety disorders (it's affinity for sigma receptors may confer a specific action) and in psychotic depression. Mirtazapine may be a treatment of interest when a fast remission of depressive symptoms (especially insomnia) is warranted but its tolerance profile makes it difficult to use. PMID- 26367398 TI - Upper digestive stenosis due to a hydatid cyst of the liver. AB - The complications of the hydatid cyst of the liver are dominated by infection and rupture. The compression of adjacent organs (mainly the inferior vena cava, the portal vein and the bile ducts) can be seen, when the cyst is located in the dome, in the hilum or within the hepatic parenchyma. Upper digestive stenosis by compression of the duodenum by the hydatid cyst is an exceptional complication. CASE REPORT: A 63 year-old patient had, for two months, upper digestive stenosis associated with a sensation of weight in the right hypochondrium. Digestive endoscopy showed an extrinsic compression of the second portion of the duodenum. Biopsies were negative. Abdominal CT showed up a hydatid cyst in the segment VI of the liver, adhering to the duodenum, with an exo-vesiculation compressing it. The patient was operated on: There was a hydatid cyst of the right lateral sector compressing the duodenum. A partial intralamellar pericystectomy was performed. CONCLUSION: Hydatid cyst of the liver, a parasitic disease described as benign, may give mechanical complications related to compression of adjacent organs (especially the bile ducts and veins). Compression of the digestive tract is exceptional. This is due to the proximity of the cyst to the duodenum and the thickness of the cyst wall. PMID- 26367399 TI - Percutaneous treatment versus hepatic resection for the treatment of small hepatocellular carcinoma. AB - BACKGROUND: Hepatocellular carcinoma is the first liver tumor worldwide. Therefore, it is a matter of debate whether surgical treatment or percutaneous treatment should be preferred for the treatment of patients with small hepatocellular carcinoma. The aim of our study was to compare the long-term outcome and the survival between surgically and percutaneously treated small hepatocellular carcinomas. MATERIAL AND METHODS: A retrospective study was performed in the department of hepatology during a period of 2009-2012. The study included all patients carrying small hepatocellular carcinoma which were divided in: group 1 including patients who underwent surgical treatment, and group 2 including patients who underwent percutaneous treatment. RESULTS: Among the 63 patients who were diagnosed for hepatocellular carcinoma, 28 carried a small hepatocellular carcinoma with a mean age of 63 years and sex-ratio of 0.64. Etiology of cirrhosis was viral in 96% cases. Surgical treatment (hepatic resection) was performed in 54% cases while percutaneous treatment was proposed for 46%: radiofrequency ablation in 69% and alcoholic injection in 31%. No major complications for both surgical and percutaneous treatment occurred in our study. The corresponding 6 months and 1- year overall survival rates for the surgical resection group and the percutaneous treatment group were 100%, 100%, 20%, and 52%, respectively (p=0,04). The disease free survival were not significantly different. CONCLUSION: Our results showed the efficacy and safety of percutaneous ablation treatments (radiofrequency ablation and ethanol injection) in patients with small hepatocellular carcinoma. PMID- 26367400 TI - Quality indicators for colonoscopy in a Tunisian endoscopy unit. AB - BACKGROUND: Colonoscopy is a powerful tool for prevention and early diagnosis of colorectal cancer. However, the effectiveness of colonoscopy is dependent on the quality of the procedure, which is assessed by a number of key quality indicators. Among them, cecal intubation and adenoma detection rate are historically the most commonly used indicators of quality of colonoscopy. The aim of our study was to evaluate these two indicators of quality of colonoscopy in a Tunisian endoscopy center. METHODS: We conducted a retrospective study from January 2009 to March 2013. Data were collected from colonoscopies reports. Demographic data, indication of the procedure, and endoscopic diagnosis were collected. The quality of bowel preparation was subjectively classified at the time of the examination by each endoscopist as good, fair, or poor. Procedure related quality indicators considered for analysis were: cecal intubation rate (CIR) and polyp detection rate. RESULTS: During the period of the study, 859 colonoscopies were performed without sedation. The average age was 54.76 +/- 17.5 years. Males represented the majority of our population (50.2%). Colic preparation was judged good, fair and poor in respectively 24 %, 61% and 15% of cases. The cecal intubation rate was 61.1 %. Causes of incomplete colonoscopy were especially poor preparation (47.3%) and poor tolerance (34.4%). Univariate analysis disclosed 3 predictive factors of CIR : the quality of bowel preparation (good vs fair or poor( (67.2 % vs 31.3%, p = 0.0001,OR: 4.5, 95% CI: 3.3-6), the screening indication (72.9% vs 60.1% , p = 0.03, OR: 1.7, 95% CI: 1-3) and the presence of alarming signs (55% vs 43%, p=0.04; OR: 1.1, 95% CI:0.9-2.5). By multivariate analysis, the factors influencing independently the CIR were the quality of bowel preparation (p=10-3, OR=2.23, 95% CI: 1.47-3.3) and the screening indication (p=0.02, OR: 1.9, 95% CI: 1.1-3.4). The polyp detection rate was 21% and was correlated, in univariate analysis with: age over 47 years (p=10 3, OR:3.2, 95 % CI:2-4.9), male gender (25.1% vs 16.8%, p=0.001, OR:2.36, 95% CI: 1.4-4), the quality of the preparation (26.5% vs 19.1%, p=0.03 OR:1.4, 95% CI:0.9 -2), the presence of colorectal cancer (50.9% vs 18.2%, p=0.0001, OR:4.6, 95% CI: 2.6-8) and the screening indication (35.7% vs 19%, p=0.001 OR: 2.36, 95% CI: 1.4- 4). By multivariate analysis, 3 independent factors associated with polyp detection rate were identified: age over 47 years (p=10-3, OR: 3.5 95% CI:2-5.9), bowel preparation (p=10-3 OR=5, 95% IC:2.7-9.6) and the screening indication( p=0.01, OR 2.5, 95% IC 1.4-4.7). CONCLUSION: In our cohort, the quality of bowel preparation, tolerance of the procedure, age and the indication of colonoscopy were significantly associated with the indicators of quality. Bowel preparation and tolerance are targets on which we should act to improve performance. PMID- 26367401 TI - [Smoking cessation attitudes among adult smokers]. AB - AIM: The failure of attempts to quit smoking was the cause of stagnation even the increasing prevalence of smoking in Tunisia. The aim of our study was to describe the previous quit attempts among smokers, the degree of motivation to the next stop and analyze the associated factors. METHODS: We carried out a survey based on an anonymous selfadministered questionnaire on tobacco, targeting smokers who participated in awareness sessions conducted in public places and universities in the city of Monastir. RESULTS: Nine hundred fourteen smokers had participated in our study. More than 2/3 of them (70 %) had at least one quit attempt, which lasted longer than 6 months for 81 patients (9%) and the last attempt dated for over 6 months for 486 smokers (53%). These previous attempts were unaccompanied and non-medicalized in 97 % of cases. 2/3 of smokers (67%) had a very strong desire to quit smoking, and 41% had a very strong self-confidence to succeed in their attempts. According to multivariate analysis, the presence of previous quit attempts to stop was statistically related to the importance of quitting smoking (OR=2.20,95% CI [1.23 - 3.96]). Selfconfidence to successfully stop was statistically related to the duration of smoking (OR=1.03 , 95% CI [1.01 - 1.06] ) , the strong dependence (OR=0.53 ;95% CI [ 0.29 - 0.97 ]) , and having at least one smoking member of the family (OR = 0.36 , 95% CI [0.15 - 0.86]). CONCLUSION: These results show that the strong physical dependence is a major factor related to the failure of attempts to quit, to the loss of self-confidence to succeed new attempts among smokers and thus, maintain a fairly high smoking prevalence in a country like Tunisia. PMID- 26367402 TI - [Quality of the medical record notification in primary health care]. AB - BACKGROUND: The medical record is a very important tool for organizing, the planning and tracking of care. Her outfit is considered as one of the major criteria for care quality. AIM: compare, the degree of given collected notification on the Structured Medical Record (SMR) in Subjective, Pre appreciation, Objective, Appreciation and Post-appreciation (SPOAP) and on Not Structured Medical Record (NSMR). METHODS: It is a retrospective, analytic study, including 910 DM. Executed in four primary health centers, at Monastir governorate in 2010. As regards methodology, we conducted a sampling at 3 degrees. The first draw of the month, the second on the weeks, the third is systematic type of medical records with a step of sounding of 2. We collected information about patient's socio-demographic characteristics, the contact patterns, clinical examination of the data, assumptions and diagnostics procedures. We used chi2 test to compare the distribution between SMR and NSMR at the Threshold of 5 %. RESULTS: Four hundred and one SMR (44 %) and 509 (56 %) NSMR were included. The contact patterns was noted on 44 % of NSMR and 93% of SMR (< 10-4). The physical examination had been noted on 67 % of SMR and 8% of NSMR (p < 10-4), the hypotheses diagnoses on 72 % of SMR and 31 % of NSMR (p < 10-4). The conducts had been noted on 98 % of SMR and 95% of NSMR (p < 0,045). The distribution of the motives for contacts, physical acts, hypotheses diagnoses and therapeutic families were different between SMR and NSMR. The medical records was adequate in 52 % of SMR and in 2% of NSMR (p < 10-4). CONCLUSION: The use of SMR improves the notification and the care continuity. PMID- 26367403 TI - New Robbins device to evaluate antimicrobial activity against bacterial biofilms on central venous catheters. AB - BACKGROUND: Layouts of biomedical devices were tightly related with the emergence of Staphylococcus epidermidis as a major cause of nosocomial infections because of its ability to form biofilm on the biomaterial surfaces. This fact led researchers to develop in-vitro models to simulate what is really happening during biofilm formation process in order to have a better understanding of this phenomena and then to control it and to resolve the associated problems. The aim of this paper was to develop a homemade dynamic device based on instruments used in clinical practice, easy to mount, with low coast and with no sophisticated features. METHODS: used to evaluate this dispositive were hydrodynamic calculation and enumeration of bacterial cells on petri dishes and with real time polymerase chain reaction during simulation of Staphylococcus epidermidis biofilm eradication with daptomycin. RESULTS: With hydrodynamic calculation, Reynolds number was estimated to be 26.62 corresponding to a perfect laminar flux giving suitable dynamic growth environment for such experiment. Data recovered from cell enumeration with the two methods showed that bacterial colonization of the tested catheter segment was significantly reduced after 24 and 48h of treatment with daptomycin (P<0.01) reflecting a considerable reliability of this device. CONCLUSION: the simple dispositive developed in this work has shown acceptable hydrodynamic proprieties and good reliability making research on biofilm easy to reach. PMID- 26367404 TI - Azathioprine for glucocorticoid resistant noninfectious uveitis. AB - BACKGROUND: the systemic steroids represent the first line treatment in the majority of the noninfectious uveitis, except some specific indications as the Behcet disease. Nevertheless, this treatment may be ineffective and immunosuppressive therapy is mandatory. PURPOSE: to evaluate effectiveness and side effects of azathioprine (AZA) in corticosteroid resistant noninfectious uveitis (CRNIU). METHODS: This prospective study (2002- 2009), concerned 21 patients (mean age 37 years), 37 eyes, with CRNIU. Patients received oral AZA 2,5mg/kg/day, initiated in association with high dose steroids, with an end-point of 12 months. Response was defined as complete, partial response and failure, for each of the 3 following out-come measurements: improvement of BCVA, improvement of inflammation, steroids-sparing. Statistical analysis was considered significant if p value < 0,05. RESULTS: side effects occurred in 42,8% (9/21) of patients, in which 5/9 patients stopped the treatment. Regarding BCVA, complete success was observed in 62,5%, partial response in 20,9% , and failure in 16,6% of cases. Regarding inflammation, complete success was noted in 70,8%, partial response in 29,1% and failure in 16,6 % of cases. Complete response of steroid sparing was observed in 85,7% of cases without failure. Complete success of the 3 criteria was observed in 57,1% of patients / 62,5% of eyes. Cataract (p=0,013) and pallor of optic nerve head (p=0,013) were associated to poor visual prognosis, BCVA of 20/40 or more (p=0,003, RR=2,38)) and papilledema (p=0,022, RR=2) to good visual prognosis. BCVA of 20/200 or less (p=0,001) was associated to failure of AZA on inflammatory response. CONCLUSION: AZA is safe and effective in corticosteroid-sparing and controlling inflammation in CRNIU. Its low cost and availability allow proposing it as a first-line option, especially when new biological treatments are difficult to obtain. PMID- 26367405 TI - [Impact of alfuzosin 10 mg once daily on quality of life in Tunisian patients with lower urinary symptoms suggestive of benign prostatic hyperplasia]. AB - BACKGROUND: Incidence of benign prostatic hyperplasia (BPH), one of the most common conditions affecting adult men, increases dramatically after the age of 50. The various symptoms of BPH, which include lower urinary tract symptoms (LUTS), can adversely affect quality of life (QoL) and sexuality and 1-Blockers are the most frequently prescribed oral medications as first-line treatment. AIM: The objectives of this study try to evaluate QoL and sexuality in patients requiring treatment by Alfuzosin 10mg once daily according to physician decision in current practice and to identify patient's profile treated with Alfuzosin 10 mg under daily practice conditions by Tunisian urologists. METHODS: 730 patients presenting a symptomatic BPH were enrolled in this study by 40 urologists. The impact of treatment on patient's QoL and sexual dysfunction were checked at every visit before treatment and at 3 and 6 months using "International Prostate symptoms score" (IPSS) and "Male Sexual Health Questionnaire - Ejaculatory Dysfunction" (MSHQ - EJD) questionnaire. RESULTS: BPH affect Qol and near half of the patients reported sexual disorders. The treatment compliance to Alfuzosin was very good with a regular intake in 92% of the cases. Quality of life significantly improves during visits: the global IPSS score decreases from 18.8 at baseline to 9.5 at 6 months. The same favorable evolution was observed with the bother score which decreases from 4.0 at baseline to 1.6 at 6 months, and with MSHQ - EJD score which increases from 10.5 at first visit to 11.4 at 6 months. CONCLUSION: Alfuzosin 10 mg administered for 6 months provides a marked improvement in patients presenting symptomatic BPH not only on LUTS but also in QoL and sexual disorders. PMID- 26367406 TI - [Marshall syndrome: Clinical, radiological and genetical features of a Tunisian family]. AB - BACKGROUND: Marshall syndrome is a rare autosomal dominant skeletal dysplasia. It associates a particular facial dysmorphism with midface hypoplasia, ocular abnormalities and sensorineural hearing loss. It is caused by heterozygous mutations in COL11A1 gene coding the 1 chain of collagen XI. Stickler syndrome is the principal differential diagnosis of Marshall syndrome. AIM: Clinical and radiological study of Marshall syndrome in a Tunisian family with a linkage study of the COL11A1 gene to this disease. METHODS: We report the clinical and the radiological findings of a Tunisian family including 8 members affected by Marshall syndrome. The linkage of the COL11A1 gene to this disease was tested using the polymorphic microsatellite markers of DNA. RESULTS: A variability of the clinical expression of Marshall syndrome was reported. Specific Marshall phenotype and an overlapping phenotype between the Marshall and Stickler syndromes were observed among the affected members of this family. The ocular manifestations were also heterogeneous. Marshall syndrome's specific radiological signs were found. The linkage study supports the linkage of the abnormal phenotype to the COL11A1 gene. CONCLUSION: There is a variability of the clinical expression among the affected members of the study's family. We will continue searching the causative mutation to establish a clear genotype- phenotype correlation. PMID- 26367407 TI - [Athletic performance, self-esteem and temperamental profile : Which relationship?]. AB - BACKGROUND: Several authors emphasize the close relationship between self-esteem and athletic performance; such a relationship may raise the following question: by saying "strong" or "without any physical condition", is it a fair presentation of the individual's abilities or he reveals the most fundamental aspects of his personality, such as emotional temperament? OBJECTIVES: To evaluate self-esteem, physical self and temperamental profile in a group of sportsmen, and to look for a relationship between these variables and athletic performance. METHODS: We performed a cross-sectional, descriptive and analytic study in 80 young handball players of the "senior" category. We assessed self-esteem using the Rosenberg Self Esteem Scale, physical self-using the Physical Self-Inventory (PSI), and temperamental profile using the Temperament Evaluation of Memphis, Paris and San Diego Auto-questionnaire (TEMPS-A). Athletic performance was evaluated by the team coach by means of a score ranging from 1 to 10. RESULTS: High self-esteem was correlated to female gender (p=0.03), to an early start of physical activity (p<0.01), and certain dimensions of the physical self: perceived physical value (p=0.02), appearance (p<0.01), and the global score (p=0.01). Athletic performance was correlated to high self-esteem (p<0.01) and to two dimensions of the physical self: the global score (p=0.01) and the perceived physical value (p<0.01). Hyperthymic temperament was associated with high self-esteem (p=0.001). Good athletic performance was associated with hyperthymic (p<0.01) and cyclothymic (p<0.01) temperament. Low athletic performance was associated with depressive (p=0.04) and irritable (p=0.01) temperament. CONCLUSION: Our study shows the close relationship between selfesteem, temperamental profile and athletic performance. We suggest that the intervention of a psychiatrist or a psychologist aimed at improving sportsmen's' self-esteem might help to achieve better athletic performance. In this intervention, the individual temperamental profile should be taken into account. PMID- 26367408 TI - [Embryo vitrification: First Tunisian live birth following embryo vitrification and literature review]. AB - Embryo cryopreservation is an essential tool in assisted reproduction. The option to freeze gametes and embryos provides unique possibilities for patients with various indications. After a review on some of the technical details of embryo freezing the idea of vitrification compared to slow freezing is discussed. It is recognized that the slow freezing technique is still overwhelmingly applied in most human in vitro fertilization (IVF) centers, but there is mounting evidence demonstrating the benefit of vitrification. Theoretical and practical examples are now sufficient to convince the embryologist that the time has arrived to switch to the vitrification technique. We report our experience that is the first Tunisian live birth following embryo vitrification at the blastocyst stage, collected at the military hospital of Tunis-Tunisia. A 29-year-old woman presented a primary infertility of 3 years of male origin. IVF with intra cytoplasmic spermatozoid injection ICSI has been indicated. 7 blastocysts were obtained at fifth day. Two of them were replaced and ended in terminated pregnancy at 6AW. Vitrification method is a procedure which is to immerse the embryos directly into liquid nitrogen at -196 degrees C. thereby achieving descents temperature of about -2000 degrees C per minute within a secure glitter. The kit used in our laboratory is "irvine scientific" with glitter cryobiocystem. Six months later 2 blastocysts were devitrified in February 2012 and after replacement provided a normal progress pregnancy, delivery by caesarean section of a newborn male in good health. PMID- 26367409 TI - Solid pseudopapillary tumor of the pancreas with concomitant Bochdalek's hernia. The first reported case. AB - BACKGROUND: Solid pseudopapillary tumors of the pancreas are rare. The diagnosis is difficult because of its clinical and radiological polymorphism. It was described in the literature that this entity can be associated with congenital malformation. We report an exceptional case associating solid pseudopapillary tumor of the pancreas to Bochdalek's hernia. CASE REPORT: A 31 year-old woman presented with abdominal pain. Radiological findings (ultrasound, CT scan, MRI) showed a heterogeneous mass evoking a stromal tumor of duodenal origin associated to a hernia through the foramen of Bochdalek. The patient underwent tumorectomy without lymphadenectomy with a hernia repair. Pathology report confirmed the diagnosis of solid pseudopapillary tumor of the pancreas. The 3-years follow- up was uneventful. CONCLUSION: Solid pseudopapillary tumor of the pancreas is a rare benign tumor with a good prognosis after resection. Recognition of the association of congenital malformation with solid pseudopapillary tumor of the pancreas is useful as it could have implications on the diagnosis and treatment. PMID- 26367410 TI - [Management of a compressive goiter in a pregnant woman]. AB - Emergency physicians frequently encounter patients with thyroid disease. However, it is unusual for these thyroid disorders to create acute, life-threatening situations. Critical airway compression attributable to benign thyroid enlargement may occur suddenly and require urgent treatment. CASE REPORT: We report a case of pregnant women who was admitted for compressive goiter with laryngeal dyspnea, which required emergency total thyroidectomy. CONCLUSION: Urgent thyroidectomy in pregnant women can be performed if we respect the precautions. PMID- 26367411 TI - [Inaugural paraneoplastic neurological syndromes]. PMID- 26367412 TI - [Renal tumor or thyroid metastasis? A case report]. PMID- 26367413 TI - [Paraspinal hydatid cyst: A rare localization of hydatidosis]. PMID- 26367414 TI - [Desmoid fibromatosis of the lower limb]. PMID- 26367415 TI - [Rare metastasis of a pulmonary adenocarcinoma]. PMID- 26367416 TI - [Sjogren's syndrome revealed by respiratory failure]. PMID- 26367417 TI - [Emphysematous pyelonephritis associated with emphysematous cystitis: case report of favorable evolution with medical treatment]. PMID- 26367418 TI - [Catastrophic postpartum antiphospholipid syndrome simulating peritonitis; a diagnostic trap]. PMID- 26367419 TI - [Posttraumatic subperiosteal orbital hematoma revealed by ocular motility impairment]. PMID- 26367420 TI - [Jarisch-Herxheimer reaction after antitubercular treatment of an intraocular tuberculosis]. PMID- 26367421 TI - Antiviral therapy for hepatitis C virus infection, cryoglobulinemic glomerulonephritis and low-grade malignant lymphoma: A challenge? PMID- 26367422 TI - Small RNA Sequencing Based Identification of MiRNAs in Daphnia magna. AB - Small RNA molecules are short, non-coding RNAs identified for their crucial role in post-transcriptional regulation. A well-studied example includes miRNAs (microRNAs) which have been identified in several model organisms including the freshwater flea and planktonic crustacean Daphnia. A model for epigenetic-based studies with an available genome database, the identification of miRNAs and their potential role in regulating Daphnia gene expression has only recently garnered interest. Computational-based work using Daphnia pulex, has indicated the existence of 45 miRNAs, 14 of which have been experimentally verified. To extend this study, we took a sequencing approach towards identifying miRNAs present in a small RNA library isolated from Daphnia magna. Using Perl codes designed for comparative genomic analysis, 815,699 reads were obtained from 4 million raw reads and run against a database file of known miRNA sequences. Using this approach, we have identified 205 putative mature miRNA sequences belonging to 188 distinct miRNA families. Data from this study provides critical information necessary to begin an investigation into a role for these transcripts in the epigenetic regulation of Daphnia magna. PMID- 26367425 TI - Necessary and sufficient conditions for the appearance of a reflectance minimum at oblique incidence when unpolarized or circularly polarized light is reflected at a dielectric-conductor interface. AB - The appearance of a reflectance minimum at oblique incidence when unpolarized or circularly polarized light is reflected at a dielectric-conductor interface requires that the normal-incidence intensity reflectance R(0) of the interface be >1/3 [J. Opt. Soc. A9, 957 (1992)10.1364/JOSAA.9.000957; Appl. Opt.53, 7885 (2014)APOPAI0003-693510.1364/AO.53.007885]. However, R(0) 1/3 is only a necessary but insufficient condition for the interface reflectance to exhibit a minimum at non-normal incidence. A second condition, the subject of this study, restricts the normal-incidence reflection phase shift delta(0) for s-polarized light to one of two non-overlapping bands: (a) 0<=delta(0)2-norm regularized regression is used to learn the correlation between edge moments and illuminants. In the testing phase, estimations from each subspace are fused in a soft way according to the posterior possibility of the test image caused by the MoG. Extensive experiments on the standard datasets including the intra- and inter-dataset evaluations show that our approach outperforms the state-of-the-art algorithms. PMID- 26367441 TI - Tight focusing of femtosecond radially polarized light pulses through a dielectric interface. AB - Based on the Richards-Wolf vector diffraction theory, we have derived the expressions for the electric field and the propagation velocity of femtosecond radially polarized light pulses focused by a high numerical aperture (NA) objective. The intensity distribution in the focus, wavefront spacings, and propagation velocity variation near the focus are investigated in detail by using numerical calculations. It is found that the propagation velocity of focused ultrashort light pulses changes dramatically near the focus, and the propagation velocity of the focused laser pulse is strongly dependent on the NA of an objective and the refractive index of media. Moreover, the usual propagation velocity of light pulses, as expected, decreases as the refractive index of media increases. PMID- 26367442 TI - Spatial properties of fundus reflectance and red-green relative spectral sensitivity. AB - We investigated the spatial characteristics of the diffuse light in the eye at two different wavelengths and the extent to which this may affect red-green relative spectral sensitivity. The fundus reflectance of six subjects was measured for different field sizes ranging from a 0.18 degrees to 7.28 degrees radius and for two different wavelengths, 560 and 650 nm. The experimental setup consisted of having an instrument project uniform disks on the fundus and recording their retinal images after a double pass through the eye. Additionally, the relative spectral sensitivity for the same wavelengths was measured using heterochromatic flicker photometry for a stimulus of a 0.4 degrees radius with and without the presence of a synchronously flickering concentric annulus. We concluded that although light backscattered from the fundus contributes to vision, the effect is not strong and can only be observed under appropriate laboratory conditions. This suggests that diffuse light from deeper fundus layers is unlikely to have a practical relevance to vision. PMID- 26367443 TI - Metal slab superlens-negative refractive index versus inclined illumination: discussion. AB - I describe experiments using a combination of an optical microscope and a plasmonic ultrathin condenser (UTC). The UTC's structure is similar to the original proposal of a silver slab superlens. I show that the observed improvement in image resolution is determined by the well-known equation describing the resolution obtainable when a condenser is included in the microscope setup. I argue that the described experiments indicate that the so called metal slab superlens is better described as a novel ultrathin microscope condenser, and the observed improvement in resolution is due to the illumination of the object under observation with inclined light produced by the plasmonic UTC. Implications of this opinion for the development of an optical nanoscope based on plasmonic UTCs are presented. PMID- 26367444 TI - Correction: Differential Contribution of Acute and Chronic Inflammation to the Development of Murine Mammary 4T1 Tumors. PMID- 26367445 TI - Structural and functional evolution of 2',3'-cyclic nucleotide 3' phosphodiesterase. AB - 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) is an abundant membrane associated enzyme within the vertebrate myelin sheath. While the physiological function of CNPase still remains to be characterized in detail, it is known - in addition to its in vitro enzymatic activity - to interact with other proteins, small molecules, and membrane surfaces. From an evolutionary point of view, it can be deduced that CNPase is not restricted to myelin-forming cells or vertebrate tissues. Its evolution has involved gene fusion, addition of other small segments with distinct functions, such as membrane attachment, and possibly loss of function at the polynucleotide kinase-like domain. Currently, it is unclear whether the enzymatic function of the conserved phosphodiesterase domain in vertebrate myelin has a physiological role, or if CNPase could actually function - like many other classical myelin proteins - in a more structural role. This article is part of a Special Issue entitled SI: Myelin Evolution. PMID- 26367446 TI - Expression of Nogo receptor 1 in microglia during development and following traumatic brain injury. AB - As the receptor of myelin associated inhibitory factors Nogo receptor 1 (NgR1) plays an important role in central nervous system (CNS) injury and regeneration. It is found that NgR1 complex acts in neurons to transduce the signals intracelluarly including induction of growth cone collapse, inhibition of axonal regeneration and regulation of nerve inflammation. In recent studies, NgR1 has also been found to be expressed in the microglia. However, NgR1 expressed in microglia in the developing nervous systems and following CNS injury have not been widely investigated. In this study, we detected the expression and cellular localization of NgR1 in microglia during development and following traumatic brain injury (TBI) in mice. The results showed that NgR1 was mainly expressed in microglia during embryonic and postnatal periods. The expression levels peaked at P4 and decreased thereafter into adulthood, while increased significantly with aging representatively at 17 mo. On the other hand, there was no significant difference in the number of double positive NgR1(+)Iba1(+) cells between normal and TBI group. In summary, we first detected the expression of NgR1 in microglia during development and found that NgR1 protein expression increased significantly in microglia with aging. These findings will contribute to make a foundation for subsequent study about the role of NgR1 expressed in microglia on the CNS disorders. PMID- 26367447 TI - Axon ensheathment and metabolic supply by glial cells in Drosophila. AB - Neuronal function requires constant working conditions and a well-balanced supply of ions and metabolites. The metabolic homeostasis in the nervous system crucially depends on the presence of glial cells, which nurture and isolate neuronal cells. Here we review recent findings on how these tasks are performed by glial cells in the genetically amenable model organism Drosophila melanogaster. Despite the small size of its nervous system, which would allow diffusion of metabolites, a surprising division of labor between glial cells and neurons is evident. Glial cells are glycolytically active and transfer lactate and alanine to neurons. Neurons in turn do not require glycolysis but can use the glially provided compounds for their energy homeostasis. Besides feeding neurons, glial cells also insulate neuronal axons in a way similar to Remak fibers in the mammalian nervous system. The molecular mechanisms orchestrating this insulation require neuregulin signaling and resemble the mechanisms controlling glial differentiation in mammals surprisingly well. We hypothesize that metabolic cross talk and insulation of neurons by glial cells emerged early during evolution as two closely interlinked features in the nervous system. This article is part of a Special Issue entitled SI: Myelin Evolution. PMID- 26367448 TI - Involvement of caspase-3/PTEN signaling pathway in isoflurane-induced decrease of self-renewal capacity of hippocampal neural precursor cells. AB - Evidence has shown that children exposed to isoflurane anesthesia in early childhood display long-term cognitive abnormalities, and decreased self-renewal capacity of hippocampal neural precursor cells (NPCs), which are associated with cognition impairment. Caspase-3 has long been considered as a mediator in isoflurane-induced neuroapoptosis. However, accumulating data indicate that caspase-3 also plays a non-apoptotic negative regulatory role in NPCs self renewal. In this study we used in vitro NPC cultures to test whether caspase-3 and its downstream signaling effectors were involved in isoflurane-induced impairment of the self-renewal capacity of hippocampal NPCs. We showed that isoflurane exposure induced a decrease in the self-renewal capacity of hippocampal NPCs by decreasing proliferation and increasing neuronal differentiation. Furthermore, we found that isoflurane exposure significantly increased the levels of active caspase-3 and decreased the levels of phospho-PTEN under both proliferation and differentiation conditions. Inhibition of either caspase-3 with Z-DEVD-fmk or PTEN with BPV (phen) in NPCs, attenuated the isoflurane-induced decrease of their proliferation and increase of neuronal differentiation. Application of Z-DEVD-fmk also attenuated isoflurane-induced decrease in phospho-PTEN expression. Taken together, our in vitro results reveal a previously uncharacterized involvement of caspase-3/PTEN signaling in the isoflurane-induced impairment of NPCs self-renewal, and contribute to the identification of novel targets for maintaining NPCs self-renewal in isoflurane induced cognitive dysfunction. PMID- 26367449 TI - The acquisition of myelin: An evolutionary perspective. AB - It has been postulated that the emergence of vertebrates was made possible by the acquisition of neural crest cells, which then led to the development of evolutionarily advantageous complex head structures (Gans and Northcutt, 1983). In this regard the contribution of one important neural crest derivative-the peripheral myelin sheath-to the success of the vertebrates has to be pointed out. Without this structure, the vertebrates, as we know them, simply could not exist. After briefly reviewing the major functions of the myelin sheath we will ask and provide tentative answers to the following three questions: when during evolution has myelin first appeared? Where has myelin initially appeared: in the CNS or in the PNS? Was it necessary to acquire a new cell type to form a myelin sheath? Careful examination of fossils lead us to conclude that myelin was acquired 425 MY ago by placoderms, the earliest hinge-jaw fishes. I argue that the acquisition of myelin during evolution has been a necessary prerequisite to permit gigantism of gnathostome species, including the sauropods. I propose that this acquisition occurred simultaneously in the PNS and CNS and that myelin forming cells are the descendants of ensheathing glia, already present in invertebrates, that have adapted their potential to synthesize large amount of membrane in response to axonal requirements. This article is part of a Special Issue entitled SI: Myelin Evolution. PMID- 26367450 TI - New coumarin-based fluorescent melatonin ligands. Design, synthesis and pharmacological characterization. AB - The design and synthesis of a series of new fluorescent coumarin-containing melatonin analogues is presented. The combination of high-binding affinities for human melatonergic receptors (h-MT1R and h-MT2R) and fluorescent properties, derived from the inclusion of melatonin pharmacophoric elements in the coumarin scaffold, yielded suitable candidates for the development of MT1R and MT2R fluorescent probes for imaging in biological media. PMID- 26367451 TI - Molecular Characterization of Sporadic Pediatric Thyroid Carcinoma with the DNA/RNA ThyroSeq v2 Next-Generation Sequencing Assay. AB - The aim of this study was to test the hypothesis that our 60-gene DNA/RNA ThyroSeq v2 next-generation sequence (NGS) assay would identify additional genetic markers, including gene fusions in sporadic pediatric differentiated thyroid carcinomas (DTC) that had no known molecular alterations. Sporadic pediatric DTCs with informative molecular testing (n=18) were studied. We previously tested 15 cases by our standard 7-gene (BRAF, NRAS, HRAS, KRAS, RET/PTC1, RET/PTC3, PAX8/PPARg) mutation panel. Three cases were not tested previously. The standard 7-gene panel identified molecular alterations in 9 of 15 tumors (60%). Cases analyzed by ThyroSeq v2 NGS included the six previously negative cases by the standard 7-gene panel and three cases not previously tested. The NGS assay revealed new gene fusions in four of six previously negative cases (67%). These gene fusions included ETV6/NTRK3 (n=3) and TPR/NTRK1 (n=1). A point mutation (BRAF-V600E) was detected in one of three untested cases. While standard testing could identify only molecular alterations in 60% of cases, with the addition of the ThyroSeq v2 NGS, this increased to 87% (n=13/15). Some cases with chromosomal rearrangements, including ETV6/NTRK3, appear to be associated with an aggressive histopathologic phenotype, but had no documented history of radiation exposure. Additional work is needed to investigate if pediatric DTCs could benefit from a reclassification based on molecular subtypes, which may better reflect their underlying biologic potential. Our data support the use of broad gene panels for the molecular diagnostics of pediatric thyroid nodules to aid future classification, treatment, and clinical management recommendations. PMID- 26367453 TI - Reduced metabolic disease risk profile by voluntary wheel running accompanying juvenile Western diet in rats bred for high and low voluntary exercise. AB - Metabolic disease risk is influenced by genetics and modifiable factors, such as physical activity and diet. Beginning at 6 weeks of age, rats selectively bred for high (HVR) versus low voluntary running distance (LVR) behaviors were housed in a complex design with or without voluntary running wheels being fed either a standard or Western (WD, 42% kcal from fat and added sucrose) diet for 8 weeks. Upon intervention completion, percent body fat, leptin, insulin, and mediobasal hypothalamic mRNAs related to appetite control were assessed. Wheel access led to differences in body weight, food intake, and serum leptin and insulin. Intriguingly, percent body fat, leptin, and insulin did not differ between HVR and LVR lines in response to the two levels of voluntary running, regardless of diet, after the 8 wk. experiment despite HVR eating more calories than LVR regardless of diet and voluntarily running 5-7 times further in wheels than LVR. In response to WD, we observed increases in Cart and Lepr mediobasal hypothalamic mRNA in HVR, but no differences in LVR. Npy mRNA was intrinsically greater in LVR than HVR, while wheel access led to greater Pomc and Cart mRNA in LVR versus HVR. These data suggest that despite greater consumption of WD, HVR animals respond similarly to WD as LVR as a result, in part, of their increased wheel running behavior. Furthermore, high physical activity in HVR may offset the deleterious effects of a WD on adiposity despite greater energy intake in this group. PMID- 26367452 TI - Immediate post-defeat infusions of the noradrenergic receptor antagonist propranolol impair the consolidation of conditioned defeat in male Syrian hamsters. AB - Social defeat occurs when an animal is attacked and subjugated by an aggressive conspecific. Following social defeat, male Syrian hamsters fail to display species-typical territorial aggression and instead exhibit submissive or defensive behaviors even when in the presence of a non-aggressive intruder. We have termed this phenomenon conditioned defeat (CD). The mechanisms underlying CD are not fully understood, but data from our lab suggest that at least some of the mechanisms are similar to those that mediate classical fear conditioning. The goal of the present experiment was to test the hypothesis that noradrenergic signaling promotes the consolidation of CD, as in classical fear conditioning, by determining whether CD is disrupted by post-training blockade of noradrenergic activity. In Experiment 1, we determined whether systemic infusions of the noradrenergic receptor antagonist propranolol (0, 1.0, 10, or 20mg/kg) given immediately after a 15 min defeat by a resident aggressor would impair CD tested 48 h later. Hamsters that were given immediate post-training infusions of propranolol (1.0, but not 10 or 20mg/kg) showed significantly less submissive behavior than did those given vehicle infusions supporting the hypothesis that there is noradrenergic modulation of the consolidation of a social defeat experience. In Experiment 2, we demonstrated that propranolol (1.0mg/kg) given immediately, but not 4 or 24h, after defeat impaired CD tested 48 h after defeat indicating that the window within which the memory for social defeat is susceptible to beta-adrenergic modulation is temporary. In Experiment 3, we examined whether central blockade of noradrenergic receptors could recapitulate the effect of systemic injections by giving an intracerebroventricular infusion of propranolol immediately after defeat and examining the effect on CD 24h later. Centrally administered propranolol (20 MUg/3 MUl but not 2 MUg/3 MUl) was also effective in dose-dependently reducing consolidation of CD. Collectively, the present results indicate that noradrenergic activity promotes the consolidation of CD and suggest that CD is a valuable model to study the processes by which emotion and stress modulate memory in an ethologically relevant context. These data also suggest that the popular conception in the clinical literature that the anxiolytic effect of propranolol is primarily due to the drug's peripheral effects may need to be reconsidered. PMID- 26367454 TI - Is genistein neuroprotective in traumatic brain injury? AB - The concerns about negative consequences of estrogen therapy have led to introduce other strategies to obtain estrogen's benefits in the brain. The present study tests the hypothesis that a major isoflavone of soy; genistein with estrogen-like activity can be neuroprotective in traumatic brain injury (TBI). The male Wistar rats were randomly divided to four groups: sham, TBI, vehicle and genistein. The TBI was induced by Marmarou method. The brain edema and the disruption of blood-brain-barrier (BBB) were evaluated 48 h post-TBI. Genistein (15 mg/kg) or dimethyl sulfoxide (DMSO) was injected i.p., twice after TBI. The intracranial pressure (ICP), the motor performance, and the beam-walk task (WB) were determined before trauma, on trauma day (D0), and first (D1) and second (D2) days post-TBI. Genistein inhibited a development of brain edema and a BBB permeability in TBI animals. An increase of ICP and a defect in motor and WB performance were showed following TBI, in all times evaluated. An increase of ICP induced by TBI was suppressed by genistein on D1 and D2 times. Genistein improved a motor disorder induced by TBI, on D1 and D2 times. Also an increase of traversal time in WB task was suppressed by genistein in TBI animals, on D1 and D2 times. The results of this study demonstrated that genistein can be neuroprotective in TBI. Genistein inhibited the disruption of BBB, the brain edema and the increase of ICP, and the disturbance of neurobehavioral performance in TBI. PMID- 26367456 TI - Planning the mode of delivery for twin pregnancies: A web-based questionnaire. AB - Using orthogonal design, we created a questionnaire containing 16 cases of twin pregnancies. For each case, respondents indicated whether they would plan a vaginal delivery (VD) or a caesarean section (CS). We assessed the association between each variable (maternal age, parity, mode of conception, gestational age, chorionicity, body mass index, foetal growth, foetal presentation and wish for additional children) and the planned mode of delivery. A VD was planned mostly for vertex presentation of twin A (vertex-vertex vs. non-vertex-vertex, odds ratio [OR]: 0.002, 95% confidence interval [CI]: 0.001-0.003, p < 0.001). For vertex- non-vertex (vs. vertex-vertex) presentation, chances on planning a VD decreased threefold (OR: 0.29, 95% CI: 0.018-0.46, p < 0.001), although the majority of respondents would still plan a VD. In multiparous (vs. nulliparous) women, VD was chosen more often (OR: 3.24, 95% CI: 2.50-4.18, p < 0.001).Vertex presentation of twin A and multiparity were the main reasons for planning a VD. PMID- 26367455 TI - Attenuation of social interaction-associated ultrasonic vocalizations and spatial working memory performance in rats exposed to chronic unpredictable stress. AB - Exposure to unpredictable chronic mild stress (CUS) is a commonly used protocol in rats that is reported to evoke antidepressant-reversible behaviors such as loss of preference for a sweetened water solution which is taken as an analog of the anhedonia seen in major depression. However, the induction of anhedonic-like behavior by chronic mild stress, gauged by an animal's preference for sucrose solution, is not fully reproducible and consistent across laboratories. In this study, we compared a widely used behavioral marker of anhedonia - the sucrose preference test, with another phenotypic marker of emotional valence, social interaction-associated ultrasonic vocalizations as well as a marker of an anxiety like phenotype, novelty-suppressed feeding, and cognitive performance in the eight arm radial maze task in adult male Sprague-Dawley rats. Chronic four-week exposure to unpredictable mild stressors resulted in 1) attenuation of social interaction-associated ultrasonic vocalizations 2) attenuation of spatial memory performance on the radial arm maze 3) attenuation of body weight gain and 4) increased latency to feed in a novelty-suppressed feeding task. However, chronic exposure to CUS did not result in any significant change in sucrose preference at one-week and three-week intervals. Our results argue for the utility of ultrasonic vocalizations in a social interaction context as a comparable alternative or adjunct to the sucrose preference test in determining the efficacy of CUS to generate an anhedonic-like phenotypic state. PMID- 26367457 TI - Ultrasound-guided high-intensity focused ultrasound (USgHIFU) ablation for the treatment of patients with adenomyosis and prior abdominal surgical scars: A retrospective study. AB - OBJECTIVE: The aim of this paper was to retrospectively compare the therapeutic efficacy and adverse effects of ultrasound-guided high-intensity focused ultrasound (USgHIFU) treatment for adenomyotic patients with or without prior abdominal surgical scars. METHODS: From January 2011 to March 2014, 534 patients with adenomyosis were referred for HIFU treatment. Among them, 118 patients had prior abdominal surgical scars, 416 patients did not have prior abdominal surgical scars. Contrast-enhanced MRI was used to evaluate the treatment outcomes. All the adverse effects were recorded. RESULTS: All patients completed USgHIFU treatment. A fractional ablation of 74.8 +/- 27.8% was achieved in the group of patients without abdominal scars; the fractional ablation was 75.6 +/- 22.3% in the group of patients with prior abdominal surgical scars. No significant difference in fractional ablation between the two groups was observed (p > 0.05). The rate of skin burn in the group of patients with prior abdominal surgical scars was significantly higher than that in the group without abdominal scars (2.5% vs. 0.2%, p < 0.05), but it is still acceptable. CONCLUSION: The prior abdominal surgical scars have no significant influence on the effectiveness of HIFU treatment for adenomyosis. The risk of skin burn is higher in patients with abdominal scars than without, but the incidence rate is still acceptable. PMID- 26367460 TI - Exploring the Altered Dynamics of Mammalian Central Carbon Metabolic Pathway in Cancer Cells: A Classical Control Theoretic Approach. AB - BACKGROUND: In contrast with normal cells, most of the cancer cells depend on aerobic glycolysis for energy production in the form of adenosine triphosphate (ATP) bypassing mitochondrial oxidative phosphorylation. Moreover, compared to normal cells, cancer cells exhibit higher consumption of glucose with higher production of lactate. Again, higher rate of glycolysis provides the necessary glycolytic intermediary precursors for DNA, protein and lipid synthesis to maintain high active proliferation of the tumor cells. In this scenario, classical control theory based approach may be useful to explore the altered dynamics of the cancer cells. Since the dynamics of the cancer cells is different from that of the normal cells, understanding their dynamics may lead to development of novel therapeutic strategies. METHOD: We have developed a model based on the state space equations of classical control theory along with an order reduction technique to mimic the actual dynamic behavior of mammalian central carbon metabolic (CCM) pathway in normal cells. Here, we have modified Michaelis Menten kinetic equation to incorporate feedback mechanism along with perturbations and cross talks associated with a metabolic pathway. Furthermore, we have perturbed the proposed model to reduce the mitochondrial oxidative phosphorylation. Thereafter, we have connected proportional-integral (PI) controller(s) with the model for tuning it to behave like the CCM pathway of a cancer cell. This methodology allows one to track the altered dynamics mediated by different enzymes. RESULTS AND DISCUSSIONS: The proposed model successfully mimics all the probable dynamics of the CCM pathway in normal cells. Moreover, experimental results demonstrate that in cancer cells, a coordination among enzymes catalyzing pentose phosphate pathway and intermediate glycolytic enzymes along with switching of pyruvate kinase (M2 isoform) plays an important role to maintain their altered dynamics. PMID- 26367459 TI - Circulating FoxP3+ Regulatory T and Interleukin17-Producing Th17 Cells Actively Influence HBV Clearance in De Novo Hepatitis B Virus Infected Patients after Orthotopic Liver Transplantation. AB - OBJECTIVE: To longitudinally investigate the role of FoxP3+ Regulatory T cells (Treg) and interleukin17-producing T helper 17 cells (Th17) in De Novo Hepatitis B Virus infection after orthotopic Liver Transplantation (DNHB-OLT), and analyze the possible correlation between these cells and HBV clearance of the disease. METHODS: We enrolled 12 control cases after orthotopic Liver Transplantation (OLT) and 24 patients, including 12 diagnosed with DNHB-OLT and 12 diagnosed with Acute Hepatitis B Virus infection (AHB), into the study from the liver transplantation and research center at Beijing 302 Hospital. Flow cytometry was used to detect the frequencies of Treg and Th17, and ELISA was applied to detect the concentration of IL6, IL22, TGF-beta and IL2 in peripheral blood. We also measured the gene expression level by real time-quantitative PCR and protein expression using immunohistochemistry and western-blot. Furthermore, we divided DNHB-OLT patients into the clearance and non-clearance groups and examined longitudinally Th17, Treg cells at different times. RESULTS: The percentage of Treg cells, expression of FoxP3 mRNA and related anti-inflammatory cytokines such as IL2 and TGF-beta1 in the DNHB-OLT group were significantly higher than that in the AHB and OLT groups. The percentage of Th17 cells, expression of RORgammat mRNA and related pro-inflammatory cytokines such as IL17 and IL22 in the DNHB-OLT group were significantly lower than that in the AHB group, but the levels of these cytokines are very similar to the OLT group. The ratios of Treg to Th17 in the DNHB-OLT group were significantly higher than that in the OLT and AHB groups. Treg frequencies significantly correlated with HBV DNA, whereas IL17 frequencies didn't significantly correlate with ALT. In DNHB-OLT patients, the clearance group was accompanied by a rapid increase in the Th17 cells during the first 4th week and afterwards continuously decrease to the control group, together with a continuously decrease in Treg cells from the onset time point, which lead to a significant reduction in the ratios of Treg to Th17. The non-clearance group was accompanied by an increase in the Treg cells during the first 4th week and afterwards sharply decrease, together with a relatively stable and unchanged Th17 cells, which lead to a significant change in the ratios. In addition, compared to clearance group, the ratios of Treg to Th17 in non-clearance group were significantly higher at the onset point, 4th and 12th week, but no difference at 24th week. CONCLUSION: DNHB-OLT patients possessed a favorable Treg differentiation environment, accompanied by a sustained higher preferentially Treg frequencies and up-regulation of related anti-inflammatory cytokines. The immune imbalance of the ratios between Treg and Th17 existed in DNHB-OLT patients. The changes of the ratios during the DNHB-OLT events were associated with HBV clearance, which suppressed immune inflammation reaction as well as inhibited ability of specific HBV clearance and led to immune escape and chronicity. PMID- 26367458 TI - Multicopy Single-Stranded DNA Directs Intestinal Colonization of Enteric Pathogens. AB - Multicopy single-stranded DNAs (msDNAs) are hybrid RNA-DNA molecules encoded on retroelements called retrons and produced by the action of retron reverse transcriptases. Retrons are widespread in bacteria but the natural function of msDNA has remained elusive despite 30 years of study. The major roadblock to elucidation of the function of these unique molecules has been the lack of any identifiable phenotypes for mutants unable to make msDNA. We report that msDNA of the zoonotic pathogen Salmonella Typhimurium is necessary for colonization of the intestine. Similarly, we observed a defect in intestinal persistence in an enteropathogenic E. coli mutant lacking its retron reverse transcriptase. Under anaerobic conditions in the absence of msDNA, proteins of central anaerobic metabolism needed for Salmonella colonization of the intestine are dysregulated. We show that the msDNA-deficient mutant can utilize nitrate, but not other alternate electron acceptors in anaerobic conditions. Consistent with the availability of nitrate in the inflamed gut, a neutrophilic inflammatory response partially rescued the ability of a mutant lacking msDNA to colonize the intestine. These findings together indicate that the mechanistic basis of msDNA function during Salmonella colonization of the intestine is proper production of proteins needed for anaerobic metabolism. We further conclude that a natural function of msDNA is to regulate protein abundance, the first attributable function for any msDNA. Our data provide novel insight into the function of this mysterious molecule that likely represents a new class of regulatory molecules. PMID- 26367461 TI - Natural incidence of zearalenone in Croatian pig feed, urine and meat in 2014. AB - The aim of this study was to determine the levels of zearalenone (ZEN) in different feed materials and feedstuffs for pigs, as well as in pig urine and pig meat following contaminated feed consumption. In total, 253 feed material and feedstuff samples were collected from Croatian pig farms. The results revealed the presence of ZEN in significant concentrations, the maximal being found in maize (5522 ug/kg), wheat (3366 ug/kg) and pig fattening feed (1949 ug/kg). In farms in which high feed contamination and pig hyperestrogenism were observed, samples of pig urine (n=30) and meat (n=30) were retrieved as well. The mean ZEN concentrations in pig urine and pig meat were 206+/-20.6 ug/L and 0.62+/-0.14 ug/kg, respectively. Despite high contamination of feedstuffs responsible for farmed pigs' intoxication, ZEN levels determined in pig meat were shown to be of little significance for human safety. PMID- 26367462 TI - Propylthiouracil Attenuates Experimental Pulmonary Hypertension via Suppression of Pen-2, a Key Component of Gamma-Secretase. AB - Gamma-secretase-mediated Notch3 signaling is involved in smooth muscle cell (SMC) hyper-activity and proliferation leading to pulmonary arterial hypertension (PAH). In addition, Propylthiouracil (PTU), beyond its anti-thyroid action, has suppressive effects on atherosclerosis and PAH. Here, we investigated the possible involvement of gamma-secretase-mediated Notch3 signaling in PTU inhibited PAH. In rats with monocrotaline-induced PAH, PTU therapy improved pulmonary arterial hypertrophy and hemodynamics. In vitro, treatment of PASMCs from monocrotaline-treated rats with PTU inhibited their proliferation and migration. Immunocyto, histochemistry, and western blot showed that PTU treatment attenuated the activation of Notch3 signaling in PASMCs from monocrotaline treated rats, which was mediated via inhibition of gamma-secretase expression especially its presenilin enhancer 2 (Pen-2) subunit. Furthermore, over expression of Pen-2 in PASMCs from control rats increased the capacity of migration, whereas knockdown of Pen-2 with its respective siRNA in PASMCs from monocrotaline-treated rats had an opposite effect. Transfection of PASMCs from monocrotaline-treated rats with Pen-2 siRNA blocked the inhibitory effect of PTU on PASMC proliferation and migration, reflecting the crucial role of Pen-2 in PTU effect. We present a novel cell-signaling paradigm in which overexpression of Pen 2 is essential for experimental pulmonary arterial hypertension to promote motility and growth of smooth muscle cells. Propylthiouracil attenuates experimental PAH via suppression of the gamma-secretase-mediated Notch3 signaling especially its presenilin enhancer 2 (Pen-2) subunit. These findings provide a deep insight into the pathogenesis of PAH and a novel therapeutic strategy. PMID- 26367463 TI - Safety performance of traffic phases and phase transitions in three phase traffic theory. AB - Crash risk prediction models were developed to link safety to various phases and phase transitions defined by the three phase traffic theory. Results of the Bayesian conditional logit analysis showed that different traffic states differed distinctly with respect to safety performance. The random-parameter logit approach was utilized to account for the heterogeneity caused by unobserved factors. The Bayesian inference approach based on the Markov Chain Monte Carlo (MCMC) method was used for the estimation of the random-parameter logit model. The proposed approach increased the prediction performance of the crash risk models as compared with the conventional logit model. The three phase traffic theory can help us better understand the mechanism of crash occurrences in various traffic states. The contributing factors to crash likelihood can be well explained by the mechanism of phase transitions. We further discovered that the free flow state can be divided into two sub-phases on the basis of safety performance, including a true free flow state in which the interactions between vehicles are minor, and a platooned traffic state in which bunched vehicles travel in successions. The results of this study suggest that a safety perspective can be added to the three phase traffic theory. The results also suggest that the heterogeneity between different traffic states should be considered when estimating the risks of crash occurrences on freeways. PMID- 26367464 TI - Identification of tyrosinase specific inhibitors from Xanthium strumarium fruit extract using ultrafiltration-high performance liquid chromatography. AB - In this study, a strategy based on ultrafiltration-high performance liquid chromatography coupled with diode array detection (UF-HPLC-DAD) was proposed for screening tyrosinase specific inhibitors in Xanthii fructus. The false negatives were distinguished by optimizing the UF-HPLC-DAD parameters to reduce the background noise; the false positives were distinguished by introducing a blocked tyrosinase in the control group for comparison. To obtain the best blocker, the competitive experiments were performed using various known ligands. Using this strategy, three competitive inhibitors (protocatechuic acid; 3,5-di-O caffeoylquinic acid; and 1,5-di-O-caffeoylquinic acid) and one mixed-type inhibitor (chlorogenic acid) were identified. These results were verified using tyrosinase inhibition assay, kinetic analysis, and structural simulation of the complex. Our experimental results suggest that the proposed strategy could be useful for high-throughput identification of tyrosinase specific inhibitors in natural products. PMID- 26367465 TI - Application of ionic liquid-based microwave-assisted extraction of flavonoids from Scutellaria baicalensis Georgi. AB - In the present work, a rapid ionic liquid-based microwave-assisted extraction (ILMAE) method was successfully applied to simultaneous extraction of baicalin, wogonoside, baicalein and wogonin from Scutellaria baicalensis Georgi. A series of 1-alkyl-3-methylirnidazolium ionic liquids with different anions and cations were assessed for extraction efficiency, and 1-octyl-3-methylimidazolium bromide was selected as the optimal solvent. In addition, the parameters of ILMAE procedure for the four flavonoids were optimized, and the optimal ILMAE method was validated in the linearity, stability, precision and recovery. Meanwhile, the microstructures of S. baicalensis powders were observed before and after extraction with the help of a scanning electron microscope (SEM) in order to explore the extraction mechanism, and the activity of the crude enzyme solution from S. baicalensis was determined through the hydrolysis of baicalin. Finally, the extraction yields and extraction time of WaterHRE, WaterMAE, ILHRE and Chp were 5.18% (30min), 8.77% (90s), 16.94% (30min) and 18.58% (3h), respectively. The results indicated that compared with the conventional extraction approaches, ILMAE possessed great advantages in extracting flavonoids, such as the highest extraction yield (22.28%), the shortest extraction time (90s), etc. PMID- 26367467 TI - Characterization of the Gly45Asp variant of human cytochrome P450 1A1 using recombinant expression. AB - Cytochrome P450 1A1 (CYP1A1) is a heme-containing enzyme involved in metabolism of xenobiotics. CYP1A1 containing a Gly45Asp substitution has not yet been characterized. Escherichia coli expressing the Gly45Asp variant, as well as the purified variant protein, had lower CYP (i.e., holoenzyme) contents than their wild-type (WT) equivalents. The purified variant protein had reduced heme contents compared with their WT equivalents. Enhanced supplementation of a heme precursor during culture did not increase CYP content in E. coli expressing the variant, but did for the WT. Substitution of Gly45 with other residues, especially those having large side chains, decreased CYP contents of E. coli expressing the variants to a considerable extent. A 3D structure of CYP1A1 indicates that Gly45, along with other residues of the PR region, interacts with Arg77 of beta- strand 1-1, which indirectly interacts with heme. Substitution analyses suggest the importance of residues of the PR region and Arg77 in holoenzyme expression. E. coli membrane and mammalian microsomes expressing the Gly45Asp variant, as well as the purified variant protein, had reduced ethoxyresorufin O-dealkylation activities, compared with the WT equivalents. These findings suggest the Gly45Asp substitution results in a structural disturbance of CYP1A1, reducing its holoenzyme formation and catalytic activity. PMID- 26367466 TI - Cytotoxicity of HBD3 for dendritic cells, normal human epidermal keratinocytes, hTERT keratinocytes, and primary oral gingival epithelial keratinocytes in cell culture conditions. AB - Human beta-defensin 3 (HBD3) is a prominent host defense peptide. In our recent work, we observed that HBD3 modulates pro-inflammatory agonist-induced chemokine and cytokine responses in human myeloid dendritic cells (DCs), often at 20.0 MUM concentrations. Since HBD3 can be cytotoxic in some circumstances, it is necessary to assess its cytotoxicity for DCs, normal human epidermal keratinocytes (NHEKs), human telomerase reverse transcriptase (hTERT) keratinocytes, and primary oral gingival epithelial (GE) keratinocytes in different cell culture conditions. Cells, in serum free media with resazurin and in complete media with 10% fetal bovine serum and resazurin, were incubated with 5, 10, 20, and 40 MUM HBD3. Cytotoxicity was determined by measuring metabolic conversion of resazurin to resorufin. The lethal dose 50 (LD50, mean MUM+/-Std Err) values were determined from the median fluorescent intensities of test concentrations compared to live and killed cell controls. The LD50 value range of HBD3 was 18.2-35.9 MUM in serum-free media for DCs, NHEKs, hTERT keratinocytes, and GE keratinocytes, and >40.0 MUM in complete media. Thus, HBD3 was cytotoxic at higher concentrations, which must be considered in future studies of HBD3 modulated chemokine and cytokine responses in vitro. PMID- 26367468 TI - Assessment of three-dimensional joint kinematics of the upper limb during simulated swimming using wearable inertial-magnetic measurement units. AB - The analysis of the joint kinematics during swimming plays a fundamental role both in sports conditioning and in clinical contexts. Contrary to the traditional video analysis, wearable inertial-magnetic measurements units (IMMUs) allow to analyse both the underwater and aerial phases of the swimming stroke over the whole length of the swimming pool. Furthermore, the rapid calibration and short data processing required by IMMUs provide coaches and athletes with an immediate feedback on swimming kinematics during training. This study aimed to develop a protocol to assess the three-dimensional kinematics of the upper limbs during swimming using IMMUs. Kinematics were evaluated during simulated dry-land swimming trials performed in the laboratory by eight swimmers. A stereo photogrammetric system was used as the gold standard. The results showed high coefficient of multiple correlation (CMC) values, with median (first-third quartile) of 0.97 (0.93-0.95) and 0.99 (0.97-0.99) for simulated front-crawl and breaststroke, respectively. Furthermore, the joint angles were estimated with an accuracy increasing from distal to proximal joints, with wrist indices showing median CMC values always higher than 0.90. The present findings represent an important step towards the practical use of technology based on IMMUs for the kinematic analysis of swimming in applied contexts. PMID- 26367469 TI - Apocyanin, NADPH oxidase inhibitor prevents lipopolysaccharide induced alpha synuclein aggregation and ameliorates motor function deficits in rats: Possible role of biochemical and inflammatory alterations. AB - Parkinson's disease (PD), is an age-related, progressive neurodegenerative disorder that affects movement and is characterized by the loss of dopaminergic neurons in the nigrostriatal region. Although the clinical and pathological features of PD are complex, recent studies have indicated that microglial NADPH oxidase play a key role in its pathology. A little information is available regarding the role of apocyanin, an NADPH oxidase inhibitor, in ameliorating alpha-synuclein aggregation and neurobehavioral consequences of PD. Therefore, the present study evaluated its therapeutic potentials for the treatment of neurobehavioral consequences in lipolysaccharide (LPS) induced PD model. For the establishment of PD model LPS (5 MUg/5 MUl PBS) was injected into the Substantia nigra (SN) of rats. Apocyanin (10mg/kgb.wt) was injected intraperitoneal. Statistical analysis revealed that apocynin significantly ameliorated LPS induced inflammatory response characterized by NFkB, TNF-alpha and IL-1beta upregulation as assessed by ELISA. It also prevented dopaminergic neurons from toxic insult of LPS as indicated by inhibition of apoptotic markers i.e., caspase 3 and caspase 9 as depicted from RT-PCR and ELISA studies. This was further supported by TUNEL assay for DNA fragmentation. Effectiveness of apocyanin in protecting dopaminergic neuronal degeneration was further confirmed by assessment of alpha synuclein deposition as depicted by IHC analysis. Consequently, an improvement in the behavioral outcome was observed following apocyanin treatment as depicted from various behavioral tests performed. Hence the data suggests that specific NADPH oxidase inhibitors, such as apocynin, may provide a new therapeutic approach to the control of neurological disabilities induced by LPS induced PD. PMID- 26367470 TI - Electrophysiological CNS-processes related to associative learning in humans. AB - The neurophysiology of human associative memory has been studied with electroencephalographic techniques since the 1930s. This research has revealed that different types of electrophysiological processes in the human brain can be modified by conditioning: sensory evoked potentials, sensory induced gamma-band activity, periods of frequency-specific waves (alpha and beta waves, the sensorimotor rhythm and the mu-rhythm) and slow cortical potentials. Conditioning of these processes has been studied in experiments that either use operant conditioning or repeated contingent pairings of conditioned and unconditioned stimuli (classical conditioning). In operant conditioning, the appearance of a specific brain process is paired with an external stimulus (neurofeedback) and the feedback enables subjects to obtain varying degrees of control of the CNS process. Such acquired self-regulation of brain activity has found practical uses for instance in the amelioration of epileptic seizures, Autism Spectrum Disorders (ASD) and Attention Deficit Hyperactivity Disorder (ADHD). It has also provided communicative means of assistance for tetraplegic patients through the use of brain computer interfaces. Both extra and intracortically recorded signals have been coupled with contingent external feedback. It is the aim for this review to summarize essential results on all types of electromagnetic brain processes that have been modified by classical or operant conditioning. The results are organized according to type of conditioned EEG-process, type of conditioning, and sensory modalities of the conditioning stimuli. PMID- 26367471 TI - A modified beam-walking apparatus for assessment of anxiety in a rodent model of blast traumatic brain injury. AB - The elevated plus maze (EPM) is used to assess anxiety in rodents. Beam-walking tasks are used to assess vestibulomotor function. Brain injury in rodents can disrupt performance on both of these tasks. Developing novel paradigms that integrate tasks like these can reduce the need for multiple tests when attempting to assess multiple behaviors in the same animal. Using adult male rats, we evaluated the use of a modified beam-walking (MBW) apparatus as a surrogate indicator for anxiety. We used a model of blast-induced traumatic brain injury (bTBI). A total of 39 rats were assessed before and at 3, 6, 24, 72, and 168h either post- bTBI (n=33) or no-injury (n=6) using both EPM and MBW. A novel anxiety index was calculated that encompassed peeks and re-emergences on MBW. The proposed MBW anxiety index was compared with the standard anxiety index calculated from exploration into different sections of EPM. Post- bTBI, rats had an increased anxiety index when measured using EPM. Similarly, they peeked or fully emerged less out of the safe box on MBW. It was found that this novel MBW anxiety index captured similar aspects of behavior when compared to the standard anxiety index obtained from EPM. Further, these effects were dissociated from the effects of bTBI on motor function simultaneously measured on MBW. Over the course of 168h post-bTBI, rats gradually recovered on both EPM and MBW. The MBW apparatus succeeded at capturing and dissociating two separate facets of rat behavior, motor function and anxiety, simultaneously. PMID- 26367472 TI - Understanding alterations in serotonin connectivity in a rat model of depression within the monoamine-deficiency and the hippocampal-neurogenesis frameworks. AB - The monoamine-deficiency and the hippocampal-neurogenesis hypotheses of depression propose that alterations in the serotonin system and of hippocampal functionality are critical in the pathogenesis of depression. We measured the alterations in the connectivity level of the raphe nucleus in the chronic mild stress (CMS) rat model of depression using the manganese enhanced MRI method (MEMRI). Manganese ions were injected into the median raphe and their anterograde intracellular propagation was followed. Depression-like behavior was demonstrated using the sucrose preference tests. We show that the raphe's connectivity is differentially altered through chronic stress. In line with the monoamine deficiency hypothesis, the connectivity of the raphe with the basal ganglia (BG) output nuclei, the hippocampus, the habenula and the entorhinal and insular cortices was reduced in CMS rats, suggesting an overall reduction in raphe excitability. Connectivity reductions were predominantly found in the right hemisphere, strengthening previous evidence pointing at a-symmetric hemispheric involvement in depression. Despite the general reduction in raphe connectivity, enhanced connectivity was found between the raphe and the septum, suggesting that alterations are connection-specific. On the basis of our results - while yet equivocal - we further discuss the possible coupling between the serotonergic and dopaminergic systems and two distinct mechanisms (direct and indirect) in which alterations in raphe connectivity may affect hippocampal dysfunction in chronic stress, thus linking the monoamine-deficiency and the hippocampal-neurogenesis hypotheses. PMID- 26367474 TI - Emerging agents for the therapy of advanced prostate cancer. AB - Since 2010, multiple advances have been made in the field of metastatic castration-resistant prostate cancer including regulatory approvals for five new agents including androgen pathway inhibitors (enzalutamide, abiraterone acetate), immunotherapy (sipuleucel-T), cytotoxic chemotherapy (cabazitaxel) and radiopharmaceuticals (radium-223) that have improved overall survival in this patient population. Despite these advances, each therapy has only extended median survival by 3-5 months and data suggest substantial cross-resistance among them. Given these modest increments, there is a major role for the vigorous investigation of new drugs and predictive biomarkers to select suitable patients who will benefit from them. This review describes emerging promising agents and their ongoing clinical development. PMID- 26367473 TI - Extended access to methamphetamine self-administration up-regulates dopamine transporter levels 72 hours after withdrawal in rats. AB - Previous studies have demonstrated that there are persistent changes in dopamine systems following withdrawal from methamphetamine (METH). This study examined changes in striatal dopamine transporter (DAT), tyrosine hydroxylase (TH) and dopamine receptor 2 (D2) 72 h after withdrawal from METH intravenous self- administration (IVSA). Rats were given limited (1h) or extended (6h) access to METH IVSA (0.05 mg/kg/0.1 ml infusion) for 22 days. Controls did not receive METH IVSA. The rats given extended access to IVSA displayed higher METH intake during the first hour of drug access compared to rats given limited access. Extended access to METH also produced a concomitant increase in striatal DAT levels relative to drug-naive controls. There were no changes in TH or D2 levels across groups. Previous studies have reported a decrease in striatal DAT levels during protracted periods (>7 days) of withdrawal from METH IVSA. This study extends previous work by showing an increase in striatal DAT protein expression during an earlier time point of withdrawal from this drug. These results are an important step toward understanding the dynamic changes in dopamine systems that occur during different time points of withdrawal from METH IVSA. PMID- 26367475 TI - Differential Consequences of Tramadol in Overdosing: Dilemma of a Polymorphic Cytochrome P450 2D6-Mediated Substrate. AB - Tramadol is a centrally acting opioid analgesic that is prone to polymorphic metabolism via cytochrome P450 (CYP) 2D6. The generation of the active metabolite, O-desmethyltramadol, which occurs through the CYP 2D6 pathway, significantly contributes to the drug's activity. However, dosage adjustments of tramadol are typically not practiced in the clinic when treating patients who are homozygous extensive metabolizers, heterozygous extensive metabolizers, or poor metabolizers. In the event of a tramadol overdose, the consequences may be influenced importantly by the genotype or phenotype status of the subject. Depending on the individual subject's CYP 2D6 status, one may see excessive miotic-related toxicity driven by the excessive availability of O desmethyltramadol or one may manifest mydriatic-related toxicity driven by the excessive availability of tramadol. This report provides pharmacokinetic perspectives in situations of tramadol overdosing. PMID- 26367476 TI - The Rituals of Fall. PMID- 26367477 TI - Was osteomyelitis the culprit? PMID- 26367479 TI - A Retrospective Analysis of Pressure Ulcer Incidence and Modified Braden Scale Score Risk Classifications. AB - The Braden Scale is the most widely used pressure ulcer risk assessment in the world, but the currently used 5 risk classification groups do not accurately discriminate among their risk categories. To optimize risk classification based on Braden Scale scores, a retrospective analysis of all consecutively admitted patients in an acute care facility who were at risk for pressure ulcer development was performed between January 2013 and December 2013. Predicted pressure ulcer incidence first was calculated by logistic regression model based on original Braden score. Risk classification then was modified based on the predicted pressure ulcer incidence and compared between different risk categories in the modified (3-group) classification and the traditional (5-group) classification using chi-square test. Two thousand, six hundred, twenty-five (2,625) patients (mean age 59.8 +/- 16.5, range 1 month to 98 years, 1,601 of whom were men) were included in the study; 81 patients (3.1%) developed a pressure ulcer. The predicted pressure ulcer incidence ranged from 0.1% to 49.7%. When the predicted pressure ulcer incidence was greater than 10.0% (high risk), the corresponding Braden scores were less than 11; when the predicted incidence ranged from 1.0% to 10.0% (moderate risk), the corresponding Braden scores ranged from 12 to 16; and when the predicted incidence was less than 1.0% (mild risk), the corresponding Braden scores were greater than 17. In the modified classification, observed pressure ulcer incidence was significantly different between each of the 3 risk categories (P less than 0.05). However, in the traditional classification, the observed incidence was not significantly different between the high-risk category and moderate-risk category (P less than 0.05) and between the mild-risk category and no-risk category (P less than 0.05). If future studies confirm the validity of these findings, pressure ulcer prevention protocols of care based on Braden Scale scores can be simplified. PMID- 26367480 TI - Adverse Effect of Sildenafil on Healing Ischemic Wounds: Results of an In vivo Study. AB - Phosphodiesterase-5 is an enzyme that inactivates cyclic guanosine monophosphate and regulates the balance of nitric oxide (NO). NO is an important molecule synthesized during wound repair. An in vivo study was conducted to evaluate the effect of sildenafil, known to have a role in regulating the effect of NO in perfusion, on the wound healing process under ischemic conditions in rats. Reepithelialization, neovascularization, inflammatory cells, and amount and maturation of granulation tissue were scored on a scale of 0-3 (none, partial, complete but immature/thin, complete and mature, respectively). Data were analyzed using ANOVA one-way test, with statistical significance determined at P < 0.05. Forty-two (42) Sprague-Dawley rats were anesthetized, wounded with H shaped flaps, and randomized into 2 groups: 1 group received 10 mg/kg sildenafil (dissolved in 1 mL distilled water) orally via orogastric tubes and the other group received a 0.9% NaCl solution via intraperitoneal injection (0.1 mL). On days 3, 5, and 10, 7 rats from each group were sacrificed. Blinded investigators analyzed skin samples for the wound healing evaluating criteria using from hematoxylin/eosin staining under an optical microscope at 10X and 40X magnification. Histopathological analysis showed sildenafil significantly reduced reepithelialization, neovascularization, amount of granulation tissue, and number of inflammatory cells on day 3 and increased inflammatory cells on day 10 (P < 0.05). Further research is needed to clarify the potential role of oral or topically applied different doses of sildenafil for ischemic wound healing as well to evaluate its safety and efficacy when administered alone or in combination with other therapies. PMID- 26367481 TI - Dehydrated Human Amnion/Chorion Membrane as Adjunctive Therapy in the Multidisciplinary Treatment of Pyoderma Gangrenosum: A Case Report. AB - Pyoderma gangrenosum (PG) is an uncommon chronic and progressive skin disorder that can lead to severe tissue necrosis, pathergy, horrendous pain, and disfigurement if not properly and promptly diagnosed and treated. Systemic treatment traditionally consists of long-term immunosuppression. Topical care of the painful wound often represents a clinical challenge. A 77-year-old woman with multiple comorbidities including venous insufficiency and diabetes mellitus was diagnosed through exclusion with refractory, painful PG. She was managed for 3 months by a multidisciplinary team comprised of an internist, 2 dermatologists, and a podiatric wound care specialist using immunosuppressive therapy, several local wound care modalities, and supportive bandages. During that time, severe wound pain continued unabated and the affected area changed from 3 separate wounds measuring 1.4 cm x 1.0 cm x .01 cm, 1.2 cm x 0.5 cm x 0.1 cm, and 0.6 cm x 0.5 cm x 0.1 cm to 1 wound measuring 8.0 cm x 10.3 cm x 0.1 cm. At that time, dehydrated human amnion/chorion membrane (dHACM) allograft, previously reported to facilitate healing venous leg and diabetic foot ulcers, was incorporated into the treatment plan. The patient reported wound pain decreased from 10 out of 10 to 5 out of 10 within hours following application. At the 4 day follow-up visit, she reported no pain; after 1 week, the wound decreased 6.4 cm x 9.4 cm x 0.1 cm in size and after 2 months (3 applications) the wound had reduced in area from 103 cm2 to 57.96 cm2 (reduced by more than half [56%]). In this patient, following the application of dHACM as an adjunct to immunosuppressive therapy, pain receded and wound healing commenced. Additional controlled studies are needed to ascertain the generalizability of this observation. PMID- 26367482 TI - Burrowing Owls, Pulex irritans, and Plague. AB - Western Burrowing Owls (Athene cunicularia hypugaea) are small, ground-dwelling owls of western North America that frequent prairie dog (Cynomys spp.) towns and other grasslands. Because they rely on rodent prey and occupy burrows once or concurrently inhabited by fossorial mammals, the owls often harbor fleas. We examined the potential role of fleas found on burrowing owls in plague dynamics by evaluating prevalence of Yersinia pestis in fleas collected from burrowing owls and in owl blood. During 2012-2013, fleas and blood were collected from burrowing owls in portions of five states with endemic plague-Idaho, Oregon, Washington, Colorado, and South Dakota. Fleas were enumerated, taxonomically identified, pooled by nest, and assayed for Y. pestis using culturing and molecular (PCR) approaches. Owl blood underwent serological analysis for plague antibodies and nested PCR for detection of Y. pestis. Of more than 4750 fleas collected from owls, Pulex irritans, a known plague vector in portions of its range, comprised more than 99.4%. However, diagnostic tests for Y. pestis of flea pools (culturing and PCR) and owl blood (PCR and serology) were negative. Thus, even though fleas were prevalent on burrowing owls and the potential for a relationship with burrowing owls as a phoretic host of infected fleas exists, we found no evidence of Y. pestis in sampled fleas or in owls that harbored them. We suggest that studies similar to those reported here during plague epizootics will be especially useful for confirming these results. PMID- 26367483 TI - The complete chloroplast genome sequence of the medicinal plant Glehnia littoralis F.Schmidt ex Miq. (Apiaceae). AB - Glehnia littoralis F. Schmidt ex Miq is an oriental medicinal herb belonging to Apiaceae family, and its dried roots and rhizomes are known to show various pharmacological effects. The complete chlorplast genome of G. littoralis was generated by de novo assembly using whole genome sequencing data. The chloroplast genome of G. littoralis was 147 467 bp in length and divided into four distinct regions: large single copy region (93 493 bp), small single copy region (17 546 bp) and a pair of inverted repeat regions (18 214 bp). A total of 114 genes including 80 protein-coding genes, 30 tRNA genes and 4 rRNA genes were predicted and accounted for 57.1% of the chloroplast genome. Phylogenetic analysis with the reported chloroplast genomes revealed that G. littoralis is an herbal species closely related to Ledebouriella seseloides, an herbal medicinal plant. PMID- 26367484 TI - What you see is what you want to see: Motivationally relevant stimuli can interrupt current resource allocation. AB - Arousing stimuli, either threat-related or pleasant, may be selected for priority at different stages within the processing stream. Here we examine the pattern of processing for non-task-relevant threatening (spiders: arousing to some) and pleasant stimuli (babies or chocolate: arousing to all) by recording the gaze of a spider Fearful and Non-fearful group while they performed a simple "follow the cross" task. There was no difference in first saccade latencies. Saccade trajectories showed a general hypervigilance for all stimuli in the Fearful group. Saccade landing positions corresponded to what each group would find arousing, such that the Fearful group deviated towards both types of images whereas the Non-fearful group deviated towards pleasant images. Secondary corrective saccade latencies away from threat-related stimuli were longer for the Fearful group (difficulty in disengaging) compared with the Non-fearful group. These results suggest that attentional biases towards arousing stimuli may occur at different processing stages. PMID- 26367485 TI - Odontogenic epithelial stem cells: hidden sources. AB - The ultimate goal of dental stem cell research is to construct a bioengineered tooth. Tooth formation occurs based on the well-organized reciprocal interaction of epithelial and mesenchymal cells. The dental mesenchymal stem cells are the best explored, but because the human odontogenic epithelium is lost after the completion of enamel formation, studies on these cells are scarce. The successful creation of a bioengineered tooth is achievable only when the odontogenic epithelium is reconstructed to produce a replica of natural enamel. This article discusses the untapped sources of odontogenic epithelial stem cells in humans, such as those present in the active dental lamina in postnatal life, in remnants of dental lamina (the gubernaculum cord), in the epithelial cell rests of Malassez, and in reduced enamel epithelium. The possible uses of these stem cells in regenerative medicine, not just for enamel formation, are discussed. PMID- 26367486 TI - miR-101a and miR-30b contribute to inflammatory cytokine-mediated beta-cell dysfunction. AB - Inflammatory cytokines have a critical role in the progressive deterioration of pancreatic beta-cell function and development of type 1 diabetes. Prolonged exposure of beta-cells to inflammatory cytokines results in gene expression modifications, leading to loss of beta-cell function. MicroRNAs (miRNAs) are small non-coding RNAs acting as key regulators of gene expression. Here, we demonstrate that miR-101a and miR-30b are key players in cytokine-mediated beta cell dysfunction. We found that IL-1beta induces an increase in miR-101a and miR 30b in MIN6 cells, and that the two miRNAs participate in beta-cell dysfunction, including decreased insulin content, gene expression, and increased beta-cell death. miR-101a and miR-30b reduce proinsulin expression and insulin content by directly targeting the transcriptional factor Neurod1. In addition, beta-cell apoptosis mediated by miR-101a and miR-30b is associated with diminished expression level of the antiapoptotic protein Bcl2. Moreover, we show that miR 101a causes an impairment in glucose-induced insulin secretion by decreasing the expression of the transcription factor Onecut2. Taken together, our findings suggest that changes in the levels of miR-101a and miR-30b contribute to cytokine mediated beta-cell dysfunction occurring during the development and progression of type 1 diabetes. PMID- 26367487 TI - miR-21 regulates tumor progression through the miR-21-PDCD4-Stat3 pathway in human salivary adenoid cystic carcinoma. AB - miR-21, which is a putative tumor onco-miR and frequently overexpressed microRNA in various tumors, has been linked to tumor progression through targeting of tumor-suppressor genes. In this study, we sought to determine whether miR-21 has any role on tumor progression of salivary adenoid cystic carcinoma (SACC) and the possible mechanisms. We found that the level of miR-21 expression was significantly higher in SACC than that in normal salivary tissues, and it is also higher in tumors with metastasis than that without metastasis. Using an anti-miR 21 inhibitor in an in vitro model, downregulation of miR-21 significantly decreased the capacity of invasion and migration of SACC cells, whereas a pre-miR 21 increased the capacity of invasion and migration of SACC cells. To explore the potential mechanisms by which miR-21 regulate invasion and migration, we identified one direct miR-21 target gene, programmed cell death 4 (PDCD4), which has been implicated in invasion and metastasis. The suppression of miR-21 in metastatic SACC-LM cells significantly increased the report activity of PDCD4 promoter and the expression of PDCD4 protein. This subsequently resulted in downregulation of the p-STAT3 protein. The level of miR-21 expression positively related to the expression of PDCD4 protein and negatively related to the expression of p-STAT3 protein in SACC specimens, respectively, indicating the potential role of the STAT3-miR-21-PDCD4 pathway in these tumors. Dysregulation of miR-21 has an important role in tumor growth and invasion by targeting PDCD4. Therefore, suppression of miR-21 may provide a potential approach for the treatment of advanced SACC patients. PMID- 26367488 TI - Attenuation of methylglyoxal-induced peritoneal fibrosis: immunomodulation by interleukin-10. AB - Peritoneal fibrosis (PF), a serious pathophysiology of peritoneal dialysis (PD), is implicated in various types of chronic inflammation. In the present study, we examined the benefits of interleukin (IL)-10, which exerts anti-inflammatory effects, in an experimental rat model of methylglyoxal (MGO)-induced PF. We injected an adeno-associated virus (AAV) vector encoding rat IL-10 or enhanced green fluorescent protein (GFP) into male Sprague-Dawley rats at 6 weeks of age. Four weeks later, the rats received continuous peritoneal injections of conventional PD fluid (PDF) with MGO for 3 weeks. Then, the peritoneal histology and the expression levels of fibrogenic mediators and proinflammatory cytokines were analyzed. The rats demonstrating persistent IL-10 expression showed significantly reduced fibrous peritoneal thickening compared with those with GFP expression. The infiltration of macrophages, the expression of tumor necrosis factor-alpha, IL-1beta, IL-6, transforming growth factor-beta1, Snail, and matrix metalloproteinase 2 genes as well as the proliferation of mesenchymal-like mesothelial cells augmented by MGO were all significantly suppressed by IL-10 expression. IL-10 also abrogated the extent of MGO-induced bowel adhesions mimicking a cocoon-like mass. Our findings provide valuable insight into the potential benefit of immunomodulation with IL-10 as one potentially effective therapeutic strategy for preventing the onset of peritoneal injury resulting in PF. PMID- 26367489 TI - Myofibroblasts contribute to but are not necessary for wound contraction. AB - Wound contraction facilitates tissue repair. The correct balance between too little contraction, which leads to non-healing wounds, and too much contraction, which leads to contractures, is important for optimal healing. Thus, understanding which cells cause wound contraction is necessary to optimize repair. Wound contraction is hypothesized to develop from myofibroblast (cells which express alpha-smooth muscle actin; ACTA2) contractility, while the role of fibroblast contractility is unknown. In this study, we utilized ACTA2 null mice to determine what role fibroblasts play in wound contraction. Human scar contractures were immunostained for ACTA2, beta-cytoplasmic actin (ACTB), and gamma-cytoplasmic actin (ACTG1). Full-thickness cutaneous wounds were created on dorsum of ACTA2(+/+) mice and strain-matching ACTA2(+/-) and ACTA2(-/-) mice. Wound contraction was quantified. Tissue was harvested for histologic, immunohistochemical and protein analysis. Compared with surrounding unwounded skin, human scar tissue showed increased expression of ACTA2, ACTB, and ACTG1. ACTA2 was focally expressed in clusters. ACTB and ACTG1 were widely, highly expressed throughout scar tissue. Wound contraction was significantly retarded in ACTA2(-/-) mice, as compared to ACTA2(+/+) controls. Control mice had increased epithelialization, cell proliferation, and neovascularization. ACTA2(-/-) mice had lower levels of apoptosis, and fewer total numbers of cells. Smaller amount of collagen deposition and immature collagen organization in ACTA2(-/-) mice demonstrate that wounds were more immature. These data demonstrate that myofibroblasts contribute to but are not necessary for wound contraction. Mechanisms by which fibroblasts promote wound contraction may include activation of contractile signaling pathways, which promote interaction between non-muscle myosin II and ACTB and ACTG1. PMID- 26367490 TI - The expression of genes involved in jejunal lipogenesis and lipoprotein synthesis is altered in morbidly obese subjects with insulin resistance. AB - The dyslipidemia associated with type 2 diabetes mellitus (T2DM) is an important risk factor for atherosclerotic cardiovascular disease. However, until now little attention has been paid to the role that the intestine might have. The aim of this research was to determine the relation between insulin resistance and intestinal de novo lipogenesis/lipoprotein synthesis in morbidly obese subjects and to study the effect of insulin on these processes. Jejunal mRNA expression of the different genes involved in the intestinal de novo lipogenesis/lipoprotein synthesis was analyzed in three groups of morbidly obese subjects: Group 1 with low insulin resistance (MO-low-IR), group 2 with high insulin resistance (MO-high IR), and group 3 with T2DM and treatment with metformin (MO-metf-T2DM). In addition, intestinal epithelial cells (IECs) from MO-low-IR were incubated with different doses of insulin/glucose. In Group 2 (MO-high-IR), the jejunal mRNA expression levels of apo A-IV, ATP-citrate lyase (ACLY), pyruvate dehydrogenase (lipoamide) beta (PDHB), and sterol regulatory element-binding protein-1c (SREBP 1c) were significantly higher and acetyl-CoA carboxylase alpha (ACC1) and fatty acid synthase lower than in Group 1 (MO-low-IR). In Group 3 (MO-metf-T2DM), only the ACLY and PDHB mRNA expressions were significantly higher than in Group 1 (MO low-IR). The mRNA expression of most of the genes studied was significantly linked to insulin and glucose levels. The incubation of IEC with different doses of insulin and glucose produced a higher expression of diacylglycerol acyltransferase 2, microsomal triglyceride transfer protein, apo A-IV, SREBP-1c, and ACC1 when both, glucose and insulin, were at a high concentration. However, with only high insulin levels, there were higher apo A-IV, PDHB and SREBP-1c expressions, and a lower ACLY expression. In conclusion, the jejunum of MO-high IR has a decreased mRNA expression of genes involved in de novo fatty-acid synthesis and an increase of genes involved in acetyl-CoA and lipoprotein synthesis. This effect is attenuated by metformin. In addition, the expression of most of the genes studied was found to be regulated by insulin. PMID- 26367491 TI - Sirtuin 1 promotes the growth and cisplatin resistance of endometrial carcinoma cells: a novel therapeutic target. AB - Sirtuin 1 (SIRT1), originally identified as a longevity gene, is induced by caloric restriction, and regulates various cellular functions including DNA repair, cell survival and metabolism via the deacetylation of target proteins such as histone and p53. These functions are considered to act dualistically as preventing or facilitating cancer. This study aimed to clarify the expression and role of SIRT1 in endometrial carcinoma. Because a high-calorie diet was a well known risk factor for endometrial carcinoma, we first hypothesized that SIRT1 might be downregulated in normal endometrial glandular cells of obese women. However, no correlation was observed between the expression of SIRT1 and body mass index (BMI). In contrast, regardless of BMI, the immunohistochemical expression of SIRT1 was significantly higher in endometrial carcinoma (108 cases) than in normal endometria (60 cases) (P<0.05), and its overexpression was associated with a shorter survival (P<0.05). Our experiments in vivo revealed that SIRT1 accelerated the proliferation of endometrial carcinoma cell lines (HHUA, HEC151, and HEC1B). SIRT1 overexpression significantly enhanced the resistance for cisplatin and paclitaxel in HHUA cells. Although p53 is an important target protein for SIRT1, the selective SIRT1 inhibitor (EX527) significantly suppressed the proliferation and cisplatin resistance of three endometrial carcinoma cell lines regardless of the p53 mutation status. In addition, SIRT1 overexpression in HHUA cells accelerated tumor growth and cisplatin resistance in nude mice, and EX527 significantly suppressed the growth of tumors of HHUA and HEC1B cells. No adverse effect of EX527 was observed in these mice. In conclusion, SIRT1 is involved in the acquisition of the aggressive behavior associated with endometrial carcinoma, and the SIRT1 inhibitor, EX527, may be a useful agent for the treatment of this malignancy. PMID- 26367492 TI - ROS-induced endothelial stress contributes to pulmonary fibrosis through pericytes and Wnt signaling. AB - Pulmonary fibrosis is a grave diagnosis with insidious progression, generally considered as a consequence of aberrant epithelial wound healing and excessive scarring. This process is commonly modeled in animals by local bleomycin administration, resulting in peribronchial inflammation and subsequent fibrosis. We have previously described initiation and early development of distal pulmonary fibrosis following repeated subcutaneous bleomycin injections (systemic administration). The aim of this study was to identify mechanisms for the development of pulmonary fibrosis, which we hypothesize is related to endothelial stress and activation. Bleomycin was administered subcutaneously 3 times/week during 0.33-4w, and parenchymal alterations were studied. In addition, we used microvascular endothelial cells to investigate effects of bleomycin in vitro. Our results confirmed that systemic administration of bleomycin exerts oxidative stress indicated by an increase in Sod1 at 0.33, 1, and 4w (P<0.05). Endothelial cells were activated (increased CD106 expression) from 1w and onwards (P<0.05), and p21 expression was increased 2-3 times throughout the study (P<0.05) as were the number of beta-catenin-positive nuclei (P<0.001). Wnt3a was increased at 0.33, 1, and 4w (P<0.01) and Wnt5a from 1w and onwards (P<0.001). The present study suggests that bleomycin-induced reactive oxygen species (ROS) causes DNA stress affecting the endothelial niche, initiating repair processes including Wnt signaling. The repeated systemic administrations disrupt a normally fine-tuned balance in the Wnt signaling. In addition, pericyte differentiation was affected, which may have significant effects on fibrosis due to their ability to differentiate into myofibroblasts. We conclude that the endothelial niche may have an important role in the development of pulmonary fibrosis and warrants further investigations. PMID- 26367493 TI - Estrogen receptor beta expression and colorectal cancer: a systematic review and meta-analysis. AB - BACKGROUND: Estrogen receptor beta (ERbeta) is a potential tumor-suppressor gene in colorectal cancer (CRC). This hypothesis is supported by clinical and laboratory observations. AIM: In this meta-analysis, we looked at studies that investigated the relationship between ERbeta protein expression and CRC, comparing the lesion with normal adjacent mucosa. METHODS: English medical literature searches were performed for ERbeta expression in patients with CRC, tumor tissue versus normal mucosa. Searches were performed up to 31 May 2015, using MEDLINE, PubMed, EMBASE, Scopus, and CENTRAL. Meta-analysis was carried out using Comprehensive Meta-analysis Software. Pooled odds ratios and 95% confidence intervals were calculated and ERbeta expression was compared in individual studies using the fixed-effects model. RESULTS: The odds ratio of ERbeta expression was 0.216 (95% confidence interval 0.152-0.307, P<0.0001), lower in cancer tissue than normal mucosa. Funnel plot did not indicate a significant publication bias. There was no significant heterogeneity in the studies included: Q=5.897, d.f.(Q)=9, I=0.000, P=0.750. CONCLUSION: In this meta-analysis, we confirm the observation of decreased ERbeta expression in CRC. Our results support the hypothesis of ERbeta being a tumor-suppressor gene in the large bowel, and the ERbeta protein protects against carcinogenesis and development of CRC when activated by estrogen. Further studies are needed to examine the potential of selective/specific ligands to activate ERbeta without the side effects found with estrogen and without activating ERalpha. SUMMARY: In this meta analysis, we looked at studies that investigated the relationship between CRC and ERbeta expression in the tumor and normal mucosa of CRC patients. English medical literature searches were performed for studies comparing ERbeta expression in the cancer and normal colonic mucosa in patients with CRC. Meta-analysis was carried out, pooled odds ratios were calculated, and ERbeta expression was compared in individual studies. PMID- 26367494 TI - Ridge Preservation After Tooth Extraction With Buccal Bone Plate Deficiency Using Tunnel Structured beta-Tricalcium Phosphate Blocks: A 2-Month Histologic Pilot Study in Beagle Dogs. AB - BACKGROUND: Reduction in alveolar ridge volume is a direct consequence of tooth extraction. Tunnel beta-tricalcium phosphate (beta-TCP) blocks were manufactured from randomly organized tunnel-shaped beta-TCP ceramic. Efficacy of these blocks compared to extraction alone for alveolar ridge preservation after tooth extraction with buccal bone deficiency was evaluated. METHODS: Maxillary first premolars of six beagle dogs were extracted after removing the buccal bone, and bone defects of 4 * 4 * 5 mm (mesio-distal width * bucco-palatal width * depth) were created. Fresh extraction sockets with buccal bone defects were filled with tunnel beta-TCP blocks at test sites. Two months after the operation, histologic and histometric evaluations were performed. RESULTS: Regarding histologic sections, coronal and middle horizontal widths of the alveolar ridge were significantly greater at test sites (3.2 +/- 0.5 and 3.6 +/- 0.4 mm, respectively) than at control sites (1.2 +/- 0.3 and 2.0 +/- 0.6 mm, respectively). The amount of woven bone was significantly greater at test sites (62.4% +/- 7.9%) than at control sites (26.8% +/- 5.3%), although that of connective tissue and bone marrow was significantly greater at control sites (38.1% +/- 6.2% and 16.0% +/- 6.9%, respectively) than at test sites (10.7% +/- 5.7% and 4.1% +/- 2.2%, respectively). Regarding basic multicellular units, no statistically significant difference was found between the test and control sites (0.5% +/- 0.1% and 0.6% +/- 0.1%, respectively). CONCLUSION: Tunnel beta-TCP blocks represent an effective bone-graft material for alveolar ridge preservation in fresh extraction sockets with buccal bone defects. PMID- 26367495 TI - Platelet-Poor and Platelet-Rich Plasma Stimulate Bone Lineage Differentiation in Periodontal Ligament Stem Cells. AB - BACKGROUND: Plasma-derived fractions have been used as an autologous source of growth factors; however, limited knowledge concerning their biologic effects has hampered their clinical application. In this study, the authors analyze the content and specific effect of both platelet-rich plasma (PRP) and platelet-poor plasma (PPP) on osteoblastic differentiation using primary cultures of human periodontal ligament stem cells (HPLSCs). METHODS: The authors evaluated the growth factor content of PRP and PPP using a proteome profiler array and enzyme linked immunosorbent assay. HPLSCs were characterized by flow cytometry and differentiation assays. The effect of PRP and PPP on HPLSC bone differentiation was analyzed by quantifying calcium deposition after 14 and 21 days of treatment. RESULTS: Albeit at different concentrations, the two fractions had similar profiles of growth factors, the most representative being platelet-derived growth factor (PDGF) isoforms (PDGF-AA, -BB, and -AB), insulin-like growth factor binding protein (IGFBP)-2, and IGFBP-6. Both formulations exerted a comparable stimulus on osteoblastic differentiation even at low doses (2.5%), increasing calcium deposits in HPLSCs. CONCLUSIONS: PRP and PPP showed a similar protein profile and exerted comparable effects on bone differentiation. Further studies are needed to characterize and compare the effects of PPP and PRP on bone healing in vivo. PMID- 26367496 TI - Gingival Crevicular Fluid Levels of Sclerostin, Osteoprotegerin, and Receptor Activator of Nuclear Factor-kappaB Ligand in Periodontitis. AB - BACKGROUND: To investigate changes in the levels and relative ratios of sclerostin, osteoprotegerin (OPG), and receptor activator of nuclear factor kappaB ligand (RANKL) in the gingival crevicular fluid (GCF) of patients with periodontitis after non-surgical periodontal treatment. METHODS: Fifty-four individuals (27 healthy controls and 27 patients with chronic periodontitis [CP]) were enrolled in the study. Periodontitis patients received non-surgical periodontal therapy. GCF sampling and clinical periodontal parameters were assessed before and 6 weeks after therapy. Sclerostin, OPG, and RANKL levels were measured by enzyme-linked immunosorbent assay, and their relative ratios were calculated. RESULTS: Total amounts and concentrations of sclerostin were significantly higher in patients with CP than in healthy individuals (P <0.025) and decreased after treatment (P <0.05). The RANKL/OPG ratio was significantly lower in healthy individuals than in patients with periodontitis before and after treatment (P <0.025), but no significant difference was observed in patients with periodontitis after treatment (P >0.05). The sclerostin/OPG and sclerostin/RANKL ratios were significantly lower in healthy individuals than in patients with periodontitis before and after treatment (P <0.025) and decreased in patients with periodontitis after treatment (P <0.05). CONCLUSIONS: The GCF sclerostin level may be more reliable than the RANKL/OPG ratio as a diagnostic and prognostic marker of periodontal disease and treatment outcome. Regulation of sclerostin levels may aid the development of new therapeutic strategies for the treatment of periodontal disease. PMID- 26367497 TI - Serum cytokine and chemokine profiles in patients with alopecia areata. AB - BACKGROUND: Most evidence supports the role of altered T cell-mediated immunity in the pathogenesis of alopecia areata (AA). Tough cytokines and chemokines play an important role in the immune process of AA, their expressions have been examined in limited studies. OBJECTIVE: To determine serum cytokine levels of TNF alpha, IL-6, and IL-23, and some of the Th1-(CXCL9), Th2-(CCL17), and Th17 associated (CCL20 and CCL27) chemokines in patients with AA. METHODS: Forty patients with AA and 40 healthy controls were enrolled in the study. Serum concentrations of cytokines and chemokines were measured using enzyme-linked immunoassay techniques. RESULTS: The mean serum levels of TNF-alpha, IL-6, IL-23, CXCL9, CCL17, CCL20, and CCL27 in AA patients were significantly higher than in the controls. However, with logistic regression analyses, only CCL17 and CCL27 levels showed a positive relationship, and IL-23 levels showed a negative relationship, with the presence of AA. Furthermore, serum CCL27 levels were positively correlated with AA severity. CONCLUSION: This study suggests that CCL17 and CCL27 may have an aggravating effect, whereas IL-23 may have a protective effect for the development of AA. Additionally, serum CCL27 levels may be useful as marker of disease severity. PMID- 26367498 TI - Functional reconstitution of an unusual Firmicutes sigma factor into a Gram negative heterologous host. AB - Sigma (sigma) factors are single-subunit proteins that reversibly bind RNA polymerase and play an important role in the transcription initiation process. An unusual 2-subunit sigma factor, consisting of proteins SigO and RsoA, activates transcription from a group of related promoters in Bacillus subtilis. These 2 proteins specifically interact with each other and with RNA polymerase subunits. This system is widespread among species in several Bacillus-related genera, but otherwise appears restricted to the Firmicutes. Here, we reconstituted SigO-RsoA, and a cognate promoter, into the distantly related heterologous host Escherichia coli to examine whether this system can function in bacteria outside of the Firmicutes. We show that these proteins can productively associate with E. coli RNA polymerase and activate transcription, demonstrating that there are no structural barriers to function. In parallel, we tested a wide array of protein protein interaction mutations and promoter mutations that impact SigO-RsoA function in both B. subtilis and E. coli and conclude that the SigO-RsoA system behaves, in most instances, similarly in both genetic backgrounds. These data raise the possibility of genetically isolating the system in this heterologous host and away from unknown B. subtilis factors that may also be playing a role in SigO-RsoA regulatory pathways, thus facilitating further study of the system. As a result of this work, we also provide a comprehensive mutational analysis of a SigO-RsoA promoter and report the preliminary identification of amino acids in SigO that play a role in mediating the SigO-RsoA protein-protein interaction. PMID- 26367499 TI - Leaves may function as temperature sensors in the heterophylly of Rorippa aquatica (Brassicaceae). AB - Many plants show heterophylly, which is variation in leaf form within a plant owing to environmental change. The molecular mechanisms underlying heterophylly have recently been investigated in several plant species. However, little is known about how plants exhibiting heterophylly sense environmental cues. Here, we used Rorippa aquatica (Brassicaceae), which shows heterophylly, to investigate whether a single leaf can sense and transit changes in ambient temperature. The morphology of newly developed leaves after single-leaf warming treatment was significantly different from that of mock-treated control leaves, suggesting that leaves are sensing organs that mediate the responses to changes in ambient temperature in R. aquatica. PMID- 26367500 TI - Impact of CYP2D6, CYP3A5, CYP2C19, CYP2A6, SLCO1B1, ABCB1, and ABCG2 gene polymorphisms on the pharmacokinetics of simvastatin and simvastatin acid. AB - OBJECTIVE: The effects of various polymorphisms in cytochrome P450 (CYP) enzyme and transporter genes on the pharmacokinetics (PK) of simvastatin were evaluated in healthy Korean men. METHODS: Plasma concentration data for simvastatin and simvastatin acid were pooled from four phase I studies comprising 133 participants. The polymorphisms CYP2D6*4, CYP2D6*5, CYP2D6*14, CYP2D6*41, CYP3A5*3, CYP2C19*2, CYP2C19*3, CYP2A6*7, and CYP2A6*9; SLCO1B1 rs4149056, rs2306283, and rs4149015; ABCB1 rs1128503, rs2032582, and rs1045642; and ABCG2 rs2231142 were evaluated in each participant. Noncompartmental PK results were compared by genotype. RESULTS: CYP2D6*5 and CYP2D6*14 were found to be associated with a higher area under the curve (AUC) for simvastatin, whereas the AUC of simvastatin acid was significantly increased in patients with the SLCO1B1 rs4149056, ABCG2 rs2231142, and CYP2D6*41 allele variants. Patients with the CYP2D6*41 variant showed a higher peak serum concentration (Cmax) of both simvastatin and simvastatin acid. The SLCO1B1 rs4149056 and rs4149015 polymorphisms were associated with an increased AUC ratio (i.e. ratio of simvastatin acid to simvastatin), whereas the SLCO1B1 rs4149056 and CYP2D6*5 variants were related to a higher Cmax ratio. CONCLUSION: The CYP2D6*5, CYP2D6*14, CYP2D6*41, CYP3A5*3, SLCO1B1 rs4149056 and rs4149015, and ABCG2 rs2231142 genetic polymorphisms are associated with the PK of both simvastatin and simvastatin acid. This could potentially be used as a basis for individualized simvastatin therapy by predicting the clinical outcomes of this treatment. PMID- 26367501 TI - Accurate interrogation of FCGR3A rs396991 in European and Asian populations using a widely available TaqMan genotyping method. AB - A polymorphism in the receptor for the Fc region of IgG, Fc gamma-receptor IIIa (FcgammaRIIIa, FCGR3A rs396991), has been inconsistently shown in the literature to have an effect on response to monoclonal antibody therapy in several indications. The rs396991 (T/G) polymorphism leads to an F176V substitution and increased affinity for IgG. This variant has proven difficult to genotype accurately, primarily because of extensive homology between the FCGR3A and FCGR3B genes. We have shown that rs396991 can be genotyped by PCR amplification, followed by direct Sanger sequencing of the product, without coamplification of FCGR3B, and that the rs396991 TaqMan assay (C__25815666_10) agrees with Sanger sequencing results in 100% of European and Asian samples tested, but it has a small error rate in African and American populations. C__25815666_10 is therefore suitable to interrogate rs396991 in studies involving Europeans and Asians; however for other populations, the default genotyping method should be PCR followed by Sanger sequencing. PMID- 26367503 TI - Considerations of red blood cell molecular testing in transfusion medicine. AB - The field of transfusion medicine is on the threshold of a paradigm shift, as the technology for genotyping of red blood cell antigens, including US FDA-approved arrays, is now moving into standard practice. Access to cost-efficient, high resolution genotyping has the potential to increase the quality of care by decreasing the risk for alloimmunization and incompatible transfusions in individuals on long-term blood transfusion protocols, including patient groups with hemoglobinopathies and other chronic diseases. Current and future applications of molecular methods in transfusion medicine and blood banking are discussed, with emphasis on indications for genotyping in various clinical scenarios. Furthermore, limitations of the current gold standard methodology and serology, as well as of contemporary molecular methodology, are examined. PMID- 26367504 TI - Anisotropic responsive microgels with tuneable shape and interactions. AB - Highly monodisperse polystyrene/poly(N-isopropylmethacrylamide) (PS-PNIPMAM) core shell composite microgels were synthesized and further nanoengineered in either ellipsoidal, faceted or bowl-shaped particles. Beside their anisotropy in shape, the microgel design enables an exquisite control of the particle conformation, size and interactions from swollen and hydrophilic to collapsed and hydrophobic using temperature as an external control variable. The post-processing procedures and the characterization of the different particles are first presented. Their potential as model systems for the investigation of the effects of anisotropic shape and interactions on the phase behavior is further demonstrated. Finally, the self-assembly of bowl-shaped composite microgel particles is discussed, where the temperature and an external AC electric field are employed to control the interactions from repulsive to attractive and from soft repulsive to dipolar, respectively. PMID- 26367502 TI - Identification of the Drosophila X chromosome: The long and short of it. AB - The different dose of X chromosomes in males and females produces a potentially fatal imbalance in X-linked gene products. This imbalance is addressed by dosage compensation, a process that modulates expression from an entire X chromosome in one sex. Dosage compensation acts on thousands of genes with disparate expression patterns. Both flies and mammals accomplish this with remarkable specificity by targeting epigenetic chromatin modifications to a single chromosome. Long noncoding RNAs that are expressed from the X chromosome are essential elements of the targeting mechanism in both lineages. We recently discovered that the siRNA pathway, as well as small RNA from satellite repeats that are strikingly enriched on the fly X chromosome, also promote X recognition. In this article we review the current understanding of X recognition in flies and discuss potential mechanisms by which the siRNA pathway, repetitive elements and long noncoding RNAs might cooperate to promote X recognition. PMID- 26367505 TI - Stereoselective Total Synthesis of KAE609 via Direct Catalytic Asymmetric Alkynylation to Ketimine. AB - A direct catalytic asymmetric alkynylation protocol is applied to provide the requisite enantioenriched propargylic alpha-tertiary amine, allowing for the stereoselective total synthesis of KAE609 (formerly NITD609 or cipargamin). PMID- 26367506 TI - The role of New Zealand health professional training institutions in capacity building in the Pacific region. PMID- 26367507 TI - Is it time to pay the PIPER? PMID- 26367508 TI - Active surveillance guidance for New Zealand men with low-risk prostate cancer. PMID- 26367509 TI - Tracking food consumption frequency of children from age 4 to 6 years: the Pacific Islands Families study. AB - AIM: To report longitudinal food frequency consumption and evaluate tracking of food frequency among a cohort of New Zealand-born Pacific children. OBJECTIVE: Identify the most commonly consumed foods and estimate tracking among Pacific children aged 4 and 6 years. METHOD: A qualitative food frequency questionnaire was administered to n>1,000 caregivers of children aged 4 and 6 years. Consumption scores were developed from averaged frequency of daily food. Foods and food groups were examined for tracking. RESULTS: Caregivers completed questionnaires for 646 children at both ages. Twelve most frequently consumed foods were identified, accounting for up to 25% of all food consumed daily. Across ages 4 and 6, the association for frequency of the most frequently consumed foods was moderate (r(2)=0.53). Food groups: breads and cereals; meat and alternates; and vegetables and fruit constituted approximately 72% of all foods consumed daily. The association of frequency of consumption within food groups across the two measurement periods was strong (r(2)=0.96). CONCLUSIONS: Pacific children consume similar foods that track from age 4 through age 6 years. PMID- 26367510 TI - Eye health outreach services in the Pacific Islands region: an updated profile. AB - BACKGROUND: Anecdotal reports indicate a decreasing number of patients presenting for assessment, and in particular a reduction in the number of patients requiring cataract surgery in Pacific Island Countries (PICs). Furthermore, research and routine surveillance is uncommon. AIM: To analyse and describe the records of eye health outreach clinics from a single provider in seven Pacific Islands. METHOD: Routine data collected at the Fred Hollows Foundation eye health outreach clinics in Fiji, Kiribati, Papua New Guinea (PNG), Samoa, the Solomon Islands, Tonga and Vanuatu between 2009 and 2013 were analysed. RESULTS: Over the study period the number of patients treated per clinic fell in Fiji, Samoa and the Solomon Islands. Data from PNG show a higher mean number of patients per clinic and the numbers of patients presenting at PNG outreach clinics appears to be increasing. Cataract was the main eye health condition for between 40%-70% of visits overall, but this range varied between 14% (PNG) and 94% (Fiji). In all countries, males were more likely to receive cataract surgery than females. Refractive error was the most common presenting complaint at PNG outreach clinics; diabetic retinopathy was most common in Tonga. Cases of trachoma or trichiasis were identified in all countries, excepting Kiribati, Samoa and Tonga. CONCLUSION: Data from outreach eye health clinics show marked differences between PICs in the most common presenting conditions. In three countries, it appears there has recently been a reduction in the overall number of patients presenting for treatment. Cautious interpretation of the data is required due to concern about data completeness and quality. PMID- 26367511 TI - Ma mahi, ka ora: by work, we prosper--traditional healers and workforce development. AB - AIM: Rongoa Maori practitioners make a valuable contribution towards Maori health outcomes, albeit with limited resourcing or formal training. This paper reports on a survey of healers/healing practices-specifically healers' aspirations for professional development and training-and considers the implications for healing practice and future training undertakings. METHODS: Healers in seven districts around the country were surveyed about rongoa practice and service delivery during 2013. Consenting healers completed surveys either in person, via phone, or returned them via post, according to their preference and convenience. Resulting data were analysed and reported according to frequency of responses. RESULTS: Thirty-eight healers/rongoa clinics completed the survey--a 79% response rate. Respondents were primarily Maori (88%), female (69%), aged 50 years or older (60%), and worked as volunteers. Informal training modes focused on te reo, matauranga and tikanga were the most common means of skill/ knowledge acquisition, and preferred modes for further training. CONCLUSIONS: The survey highlights the pressing need for expansion of the rongoa Maori workforce and training/service funding, to sustain rongoa practice. The findings add to what little is known about the training pathways and aspirations of practising healers, identified targets of the Maori Health Workforce Development Plan 2006. PMID- 26367512 TI - Factors associated with nutrition risk in older Maori: a cross sectional study. AB - AIM: To investigate factors associated with nutrition risk among older Maori. METHOD: Maori aged 75-79 years living in the Northland and Bay of Plenty regions of New Zealand were assessed for nutrition risk using the validated screening tool 'Seniors in the Community: Risk Evaluation for Eating and Nutrition' (SCREENII). Demographic, physical and sociocultural data were collected. RESULTS: Of the 67 participants, two thirds (63%) were identified to be at high-risk for malnutrition. More than half (56%) used te reo Maori (Maori language) for everyday conversation and those who rated language and culture as moderately important to wellbeing were at lower nutrition risk. Controlling for age, gender and living arrangements, participants who rated traditional foods as important, were able to access them, had a higher waist-to-hip ratio and an absence of depressive symptoms, were at lower nutrition risk. CONCLUSIONS: Cultural factors associated with nutrition risk are related to an indigenous view of health. Participants with a higher waist-to-hip ratio were at lower nutrition risk and this may be a protective factor for older Maori. Interventions to improve the nutrition status of older Maori need to be based on a holistic Maori worldview and acknowledge the importance of traditional Maori foods. PMID- 26367513 TI - A comprehensive approach to improving patient flow in our hospitals--the 'left to right, over and under' concept. AB - It is essential we manage the capacity of our hospitals so that acute demand can be accommodated without developing queues for care and backlogs of work. This paper presents a comprehensive model for improving patient flow in our hospitals by attending carefully to both the demand and capacity states of the hospital and maximising efficient flow of our acute patient journeys. The model includes attention to the patient journey as the central focus, with an overarching governance structure and an underpinning sophisticated operations structure. PMID- 26367514 TI - Urate testing in gout: why, when and how. AB - Urate is a frequently measured blood test in people with gout and those at risk of gout. Although gout is potentially curable with long-term urate lowering therapy, confusion about the details of urate measurement has contributed to suboptimal care. In this article, we provide recommendations regarding urate testing in gout, focusing on the use of this test in clinical practice. PMID- 26367515 TI - What is this condition and how could it be treated? PMID- 26367516 TI - A pain in the ass... . PMID- 26367517 TI - Excise, electronic cigarettes and nicotine reduction to reduce smoking prevalence in New Zealand by 2025. PMID- 26367518 TI - The Utility of Unplanned Early Hospital Readmissions as a Health Care Quality Indicator. PMID- 26367519 TI - Self-narrative reconstruction after dilemma-focused therapy for depression: A comparison of good and poor outcome cases. AB - OBJECTIVE: The aim of this study is to improve the understanding of self-changes after an intervention for depression focused on implicative dilemmas, a type of cognitive conflict related to identity. As recent research has highlighted the relevance of identity-related dilemmas in clients with depression, we sought to assess the way in which clients resolve such inner conflicts after a tailored dilemma-focused intervention and how this is reflected in the clients' self narratives. METHOD: We used three instruments to observe differences between good (n = 5) and poor (n = 5) outcome cases: (i) the Repertory Grid Technique to track the resolution of dilemmas, (ii) the Change Interview to compile clients' accounts of changes at posttreatment, and (iii) the Innovative Moments Coding System to examine the emergence of clients' novelties at the Change Interview. RESULTS: Groups did not differ in terms of the number and relevance of client identified significantly helpful events. However, between-group differences were found for the resolution of dilemmas and for the proportion of high-level innovative moment (IM) types. Furthermore, a greater self-narrative reconstruction was associated with higher levels of symptom improvement. CONCLUSIONS: Good outcome cases seem to be associated with the resolution of conflicts and high-level IMs. PMID- 26367520 TI - The Promotion of Medical Products in the 21st Century: Off-label Marketing and First Amendment Concerns. PMID- 26367521 TI - A simple and effective technique to prevent twisting or torsion of pedicle in microvascular free tissue transfer. PMID- 26367522 TI - Poor Folate Intake in a North Italian Pregnant Population: an Epidemiological Survey. AB - BACKGROUND: The association between folic acid (FA) insufficiency and congenital malformations has been demonstrated in over the past two decades. The aim of the present study was to investigate the use and timing of folate intake among a large sample of pregnant women in a north Italian region. METHODS: A multicentre prospective cohort study was conducted over a 14-month period in the maternity wards of five general hospitals (2301 women). Data were collected via a face-to face interview. RESULTS: Seven hundred sixty women (33%) took at least one product containing FA. Seven hundred thirty-three (31.8%) women consumed multivitamins containing 413 (17.9%) consumed products containing FA only and 17 (0.7%) 15 mg of levofolinic acid. Only 0.9% of all women took FA before pregnancy 72.5% of women who consumed FA started during the first trimester. The most common dosage was 0.4 mg (19.4%). CONCLUSIONS: Very few women in the population are taking FA before pregnancy. Moreover, while most women consuming FA started in the first trimester, it is likely that they did so after closure of the neural tube. An important action is the recommendation that periconceptional supplementation programmes be promoted. PMID- 26367523 TI - The Pressure-Induced Polymorphic Transformations in Fluconazole. AB - The structural properties and Raman spectra of fluconazole have been studied by means of X-ray diffraction and Raman spectroscopy at pressures up to 2.5 and 5.5 GPa, respectively. At a pressure of 0.8 GPa, a polymorphic phase transition from the initial form I to a new triclinic form VIII has been observed. At higher pressure of P = 3.2 GPa, possible transformation into another new polymorphic form IX has been detected. The unit cell parameters and volumes, and vibration modes as functions of pressure have been obtained for the different forms of fluconazole. PMID- 26367526 TI - Gastroenterology, Academic Medicine and a Changing Landscape. AB - The forces that are reshaping the delivery of health care through much of the developed world are especially acute within academic centers that carry the responsibility for delivering that care while advancing medical knowledge and ensuring well-trained physicians. Gastroenterology will not be spared any of those forces, and in some ways represents the leading edge of their impact. Though the dynamics vary within the context of the health-care delivery and scientific enterprise of individual countries, common elements are demands for greater accountability and transparency in how academic medical centers demonstrate their value while assuring broad access to their expertise. In the United States, underlying many forms of change in the payment scheme are the common elements that will increasingly place the risk for the cost of care on providers rather than on the payers, be it government or private, as has historically been true. At the same time, academic medical centers, with gastroenterology responsible for addressing the burden of digestive diseases, must remain the stem cells for health care integrating all their missions and providing the foundation of medical advances which will ultimately improve human welfare. What will academic gastroenterology units look like if they are able to effectively respond to these forces? Gastrointestinal (GI) divisions and faculty will own new roles including responsibility for system success in caring for patients. They will evolve their training programs to provide the next generation with skills needed to succeed, including the discipline of system improvement, team leadership and others. And there will be new models that will drive the organization of research that are not as conventionally self-contained within the gastroenterology units, but fostering research teams that have hubs and spokes. The vitality of GI divisions will depend on the willingness to seize ownership of the new value proposition of disease management ensuring that each patient achieves the best outcome with the most effective use of resources and endeavor within their systems to capture some of that value to invest in their training and research missions. In the course of that evolution, gastroenterology will be well served by rebalancing the dependence on existing modalities. If procedural gastroenterology becomes the sole value proposition, it will lead to an increasingly narrow view of the field. PMID- 26367525 TI - Interest of Antiplatelet Drug Testing after an Acute Ischemic Stroke. AB - BACKGROUND: Stroke occurrence despite chronic antiplatelet drug (APD) treatment is frequent. We aimed at evaluating the relevance of platelet aggregation testing in the identification of stroke etiology in this context. METHODS: Patients admitted for a suspected acute ischemic stroke, while under APD (aspirin and/or clopidogrel), were prospectively included. The efficacy of the APD was evaluated using a MultiplateTM assay. Resistance was confirmed using light transmission aggregometry. A standardized diagnostic work-up was performed to identify stroke mechanism according to the TOAST and the ASCO classifications. We evaluated the influence of APD functional status on stroke severity and identified potential determinants of resistance. RESULTS: APD resistance was observed in 53 of the 287 patients (18.5%). No difference in stroke mechanism depending on APD efficacy was observed. Patients sensitive to APD had less severe initial stroke severity (mean National Institutes of Health Stroke Scale 3.9 +/- 5.6 vs. 7.2 +/- 6.8; p < 0.01). Main determinants for APD resistance were a worse control of the diabetes and higher baseline levels of inflammation (mean CRP 26.4 +/- 56.0 vs. 9.3 +/- 21.0; p < 0.01). CONCLUSIONS: Platelet function testing does not provide orientation concerning stroke mechanism in patients who were previously on APDs. However, the high frequency of APD resistance and its association with inflammation and stroke severity are confirmed. PMID- 26367527 TI - Effect of Continuous Positive Airway Pressure on Adiponectin in Patients with Obstructive Sleep Apnea: A Meta-Analysis. AB - OBJECTIVE: Obstructive sleep apnea (OSA) has been suggested to be associated with low levels of adiponectin. Continuous positive airway pressure (CPAP) is the gold standard treatment for OSA; however, previous studies assessing the effect of CPAP on adiponectin in patients with OSA yielded conflicting results. The present meta-analysis was performed to determine whether CPAP therapy could increase adiponectin levels. METHODS: Two reviewers independently searched PubMed, Cochrane library, Embase and Web of Science before February 2015. Information on characteristics of subjects, study design and pre- and post-CPAP treatment of serum adiponectin was extracted for analysis. Standardized mean difference (SMD) was used to analyze the summary estimates for CPAP therapy. RESULTS: Eleven studies involving 240 patients were included in this meta-analysis, including ten observational studies and one randomized controlled study. The meta-analysis showed that there was no change of adiponectin levels before and after CPAP treatment in OSA patients (SMD = 0.059, 95% confidence interval (CI) = -0.250 to 0.368, z = 0.37, p = 0.710). Subgroup analyses indicated that the results were not affected by age, baseline body mass index, severity of OSA, CPAP therapy duration, sample size and racial differences. CONCLUSIONS: This meta-analysis suggested that CPAP therapy has no impact on adiponectin in OSA patients, without significant changes in body weight. Further large-scale, well-designed long-term interventional investigations are needed to clarify this issue. PMID- 26367528 TI - Interactions between N-linked glycosylation and polymerisation of neuroserpin within the endoplasmic reticulum. AB - The neuronal serpin neuroserpin undergoes polymerisation as a consequence of point mutations that alter its conformational stability, leading to a neurodegenerative dementia called familial encephalopathy with neuroserpin inclusion bodies (FENIB). Neuroserpin is a glycoprotein with predicted glycosylation sites at asparagines 157, 321 and 401. We used site-directed mutagenesis, transient transfection, western blot, metabolic labelling and ELISA to probe the relationship between glycosylation, folding, polymerisation and degradation of neuroserpin in validated cell models of health and disease. Our data show that glycosylation at N157 and N321 plays an important role in maintaining the monomeric state of neuroserpin, and we propose this is the result of steric hindrance or effects on local conformational dynamics that can contribute to polymerisation. Asparagine residue 401 is not glycosylated in wild type neuroserpin and in several polymerogenic variants that cause FENIB, but partial glycosylation was observed in the G392E mutant of neuroserpin that causes severe, early-onset dementia. Our findings indicate that N401 glycosylation reports lability of the C-terminal end of neuroserpin in its native state. This C terminal lability is not required for neuroserpin polymerisation in the endoplasmic reticulum, but the additional glycan facilitates degradation of the mutant protein during proteasomal impairment. In summary, our results indicate how normal and variant-specific N-linked glycosylation events relate to intracellular folding, misfolding, degradation and polymerisation of neuroserpin. PMID- 26367530 TI - Correction: The Complete Sequence of the Acacia ligulata Chloroplast Genome Reveals a Highly Divergent clpP1 Gene. PMID- 26367529 TI - Prolonged Adaptation to a Low or High Protein Diet Does Not Modulate Basal Muscle Protein Synthesis Rates - A Substudy. AB - BACKGROUND: Based on controlled 36 h experiments a higher dietary protein intake causes a positive protein balance and a negative fat balance. A positive net protein balance may support fat free mass accrual. However, few data are available on the impact of more prolonged changes in habitual protein intake on whole-body protein metabolism and basal muscle protein synthesis rates. OBJECTIVE: To assess changes in whole-body protein turnover and basal muscle protein synthesis rates following 12 weeks of adaptation to a low versus high dietary protein intake. METHODS: A randomized parallel study was performed in 40 subjects who followed either a high protein (2.4 g protein/kg/d) or low protein (0.4 g protein/kg/d) energy-balanced diet (30/35/35% or 5/60/35% energy from protein/carbohydrate/fat) for a period of 12 weeks. A subgroup of 7 men and 8 women (body mass index: 22.8+/-2.3 kg/m2, age: 24.3+/-4.9 y) were selected to evaluate the impact of prolonged adaptation to either a high or low protein intake on whole body protein metabolism and basal muscle protein synthesis rates. After the diet, subjects received continuous infusions with L-[ring 2H5]phenylalanine and L-[ring-2H2]tyrosine in an overnight fasted state, with blood samples and muscle biopsies being collected to assess post-absorptive whole body protein turnover and muscle protein synthesis rates in vivo in humans. RESULTS: After 12 weeks of intervention, whole-body protein balance in the fasted state was more negative in the high protein treatment when compared with the low protein treatment (-4.1+/-0.5 vs -2.7+/-0.6 MUmol phenylalanine/kg/h;P<0.001). Whole-body protein breakdown (43.0+/-4.4 vs 37.8+/-3.8 MUmol phenylalanine/kg/h;P<0.03), synthesis (38.9+/-4.2 vs 35.1+/-3.6 MUmol phenylalanine/kg/h;P<0.01) and phenylalanine hydroxylation rates (4.1+/-0.6 vs 2.7+/-0.6 MUmol phenylalanine/kg/h;P<0.001) were significantly higher in the high vs low protein group. Basal muscle protein synthesis rates were maintained on a low vs high protein diet (0.042+/-0.01 vs 0.045+/-0.01%/h;P = 0.620). CONCLUSIONS: In the overnight fasted state, adaptation to a low-protein intake (0.4 g/kg/d) does not result in a more negative whole-body protein balance and does not lower basal muscle protein synthesis rates when compared to a high protein intake. TRIAL REGISTRATION: Clinicaltrials.gov NCT01551238. PMID- 26367531 TI - Pitavastatin Reduces Inflammation in Atherosclerotic Plaques in Apolipoprotein E Deficient Mice with Late Stage Renal Disease. AB - OBJECTIVES: Chronic renal disease (CRD) accelerates atherosclerosis and cardiovascular calcification. Statins reduce low-density lipoprotein-cholesterol levels in patients with CRD, however, the benefits of statins on cardiovascular disease in CRD remain unclear. This study has determined the effects of pitavastatin, the newest statin, on arterial inflammation and calcification in atherogenic mice with CRD. METHODS AND RESULTS: CRD was induced by 5/6 nephrectomy in cholesterol-fed apolipoprotein E-deficient mice. Mice were randomized into three groups: control mice, CRD mice, and CRD mice treated with pitavastatin. Ultrasonography showed that pitavastatin treatment significantly attenuated luminal stenosis in brachiocephalic arteries of CRD mice. Near infrared molecular imaging and correlative Mac3 immunostaining demonstrated a significant reduction in macrophage accumulation in pitavastatin-treated CRD mice. Pitavastatin treatment reduced levels of osteopontin in plasma and atherosclerotic lesions in CRD mice, but did not produce a significant reduction in calcification in atherosclerotic plaques as assesses by histology. CRD mice had significantly higher levels of phosphate in plasma than did control mice, which did not change by pitavastatin. In vitro, pitavastatin suppressed the expression of osteopontin in peritoneal macrophages stimulated with phosphate or calcium/phosphate in concentrations similar to those found in human patients with CRD. CONCLUSION: Our study provides in vivo evidence that pitavastatin reduces inflammation within atherosclerotic lesions in CRD mice. PMID- 26367532 TI - Clinical Usefulness of Procalcitonin and C-Reactive Protein as Outcome Predictors in Critically Ill Patients with Severe Sepsis and Septic Shock. AB - Sepsis is a major cause of mortality and morbidity in critically ill patients. Procalcitonin (PCT) and C-reactive protein (CRP) are the most frequently used biomarkers in sepsis. We investigated changes in PCT and CRP concentrations in critically ill patients with sepsis to determine which biochemical marker better predicts outcome. We retrospectively analyzed 171 episodes in 157 patients with severe sepsis and septic shock who were admitted to the Samsung Medical Center intensive care unit from March 2013 to February 2014. The primary endpoint was patient outcome within 7 days from ICU admission (treatment failure). The secondary endpoint was 28-day mortality. Severe sepsis was observed in 42 (25%) episodes from 41 patients, and septic shock was observed in 129 (75%) episodes from 120 patients. Fifty-five (32%) episodes from 42 patients had clinically documented infection, and 116 (68%) episodes from 99 patients had microbiologically-documented infection. Initial peak PCT and CRP levels were not associated with treatment failure and 28-day mortality. However, PCT clearance (PCTc) and CRP (CRPc) clearance were significantly associated with treatment failure (p = 0.027 and p = 0.030, respectively) and marginally significant with 28-day mortality (p = 0.064 and p = 0.062, respectively). The AUC for prediction of treatment success was 0.71 (95% CI, 0.61-0.82) for PCTc and 0.71 (95% CI, 0.61 0.81) for CRPc. The AUC for survival prediction was 0.77 (95% CI, 0.66-0.88) for PCTc and 0.77 (95% CI, 0.67-0.88) for CRPc. Changes in PCT and CRP concentrations were associated with outcomes of critically ill septic patients. CRP may not be inferior to PCT in predicting outcome in these patients. PMID- 26367533 TI - Mannan-Binding Lectin Is Involved in the Protection against Renal Ischemia/Reperfusion Injury by Dietary Restriction. AB - Preoperative fasting and dietary restriction offer robust protection against renal ischemia/reperfusion injury (I/RI) in mice. We recently showed that Mannan binding lectin (MBL), the initiator of the lectin pathway of complement activation, plays a pivotal role in renal I/RI. Based on these findings, we investigated the effect of short-term DR (30% reduction of total food intake) or three days of water only fasting on MBL in 10-12 weeks old male C57/Bl6 mice. Both dietary regimens significantly reduce the circulating levels of MBL as well as its mRNA expression in liver, the sole production site of MBL. Reconstitution of MBL abolished the protection afforded by dietary restriction, whereas in the fasting group the protection persisted. These data show that modulation of MBL is involved in the protection against renal I/RI induced by dietary restriction, and suggest that the mechanisms of protection induced by dietary restriction and fasting may be different. PMID- 26367534 TI - Adsorption on Mesoporous Metal-Organic Frameworks in Solution: Aromatic and Heterocyclic Compounds. AB - Adsorption and desorption play major roles in separations, purification of water, waste streams, liquid fuels, catalysis, biomedicine and chromatography. Mesoporous metal-organic frameworks (MOFs) with pore sizes 2-50 nm are particularly suitable for adsorption of organic compounds in solution. Tens of thousands of aromatic and heterocyclic compounds are major components of liquid fuels, feedstock for industrial synthesis, solvents, dyestuffs, agricultural chemicals, medicinal drugs, food additives, and so forth. This Review provides a systematization and analysis of studies on adsorption/desorption on mesoporous MOFs in solution and their underlying chemical mechanisms. The (in)stability of mesoporous MOFs in water is critically discussed. Adsorption capacity and selectivity are covered for organic dyes, medicinal drugs, major components of liquid fuels, and miscellaneous industrial chemicals. Ionic interactions, Bronsted acid-base interactions, hydrogen bonding, coordination bonding, pi-pi interactions, and non-specific interactions are covered amongst adsorption mechanisms. The effects of post-synthetic modifications of mesoporous MOFs on their stability, adsorption capacity, selectivity, and mechanisms of adsorption and desorption are analyzed. To encourage research in this quickly growing field, we identify "niches" for which no application-oriented and/or mechanistic studies were reported. Perspectives and limitations of a wide use of mesoporous MOFs as industrial sorbents are discussed. PMID- 26367535 TI - Identification of Genes Whose Expression Profile Is Associated with Non Progression towards AIDS Using eQTLs. AB - BACKGROUND: Many genome-wide association studies have been performed on progression towards the acquired immune deficiency syndrome (AIDS) and they mainly identified associations within the HLA loci. In this study, we demonstrate that the integration of biological information, namely gene expression data, can enhance the sensitivity of genetic studies to unravel new genetic associations relevant to AIDS. METHODS: We collated the biological information compiled from three databases of expression quantitative trait loci (eQTLs) involved in cells of the immune system. We derived a list of single nucleotide polymorphisms (SNPs) that are functional in that they correlate with differential expression of genes in at least two of the databases. We tested the association of those SNPs with AIDS progression in two cohorts, GRIV and ACS. Tests on permuted phenotypes of the GRIV and ACS cohorts or on randomised sets of equivalent SNPs allowed us to assess the statistical robustness of this method and to estimate the true positive rate. RESULTS: Eight genes were identified with high confidence (p = 0.001, rate of true positives 75%). Some of those genes had previously been linked with HIV infection. Notably, ENTPD4 belongs to the same family as CD39, whose expression has already been associated with AIDS progression; while DNAJB12 is part of the HSP90 pathway, which is involved in the control of HIV latency. Our study also drew our attention to lesser-known functions such as mitochondrial ribosomal proteins and a zinc finger protein, ZFP57, which could be central to the effectiveness of HIV infection. Interestingly, for six out of those eight genes, down-regulation is associated with non-progression, which makes them appealing targets to develop drugs against HIV. PMID- 26367536 TI - Does Male Care, Provided to Immature Individuals, Influence Immature Fitness in Rhesus Macaques? AB - Among many mammals, maternal care strongly impacts infant survival; however, less is known about whether adult males also affect infant fitness. Paternal care is expected when providing care enhances offspring survival and reproduction, which likewise increases fathers' fitness. Males might also care for unrelated immature individuals to increase their mating probability with the immature individuals' mothers. Studies in multimale primate groups showed that sires enhance food access for offspring and provide protection in conflicts. Furthermore, fathers' presence during infancy has been suggested to accelerate offspring sexual maturation. However, no study has yet directly linked the degree of father offspring bonds to offspring fitness in primates. We previously reported father offspring affiliation in rhesus macaques, pronounced during early infancy and independent of mothers' presence. The present study aims at investigating whether affiliation with fathers or other males affects proxies of immature fitness (body mass gain, body fat and testis size). First, we combined behavioral, genetic and morphometric data from 55 subjects of one group. Second, using demographic and genetic data, we investigated for 92 individuals of the population whether mother and father-offspring co-residence during immaturity influenced offspring lifetime reproductive success (LRS). Our results show that focal rank and higher amounts of affiliation with high-ranking males during infancy tend to positively impact body mass gain of female, but not male focal animals. In contrast, body mass gain of male focal individuals, but not females', appeared to be higher when affiliation of male immature individuals was evenly distributed across their adult male partners. Moreover, we found mothers', but not fathers', presence during immaturity to predict offspring LRS. Our results suggest that male immature affiliation, but not father-offspring co-residence, potentially impacts proxies of immature fitness. However, future studies should investigate the underlying mechanisms of male-immature relationships and their impact on immature fitness in more detail. PMID- 26367537 TI - Serum Homocysteine Concentration Is Significantly Associated with Inflammatory/Immune Factors. AB - Recent studies suggest that serum homocysteine (HCY) level is correlated to inflammatory/immune factors that influence the development and progression of many diseases, such as cardiovascular disease. However, the association between serum HCY level and inflammatory/immune factors in healthy populations has not been systematically investigated. This study was conducted based on the Fangchenggang Area Male Health and Examination Survey (FAMHES) project. After comprehensive baseline analysis, we could not find any significant association between HCY level and inflammatory/immune factors. However, in the next linear regression analysis, serum C4 [age-adjusted: Beta = -0.053, 95%CI = (-3.798, 0.050), P = 0.044; multivariate adjusted: Beta = -0.064, 95%CI = (-4.271, 0.378), P = 0.019] and C-reactive protein (CRP) concentration [unadjusted: Beta = 0.056, 95%CI = (0.037, 0.740), P = 0.030] were positively related with HCY. In further binary regression analysis, a significant correlation was confirmed for C4 and HCY [age-adjusted: OR = 0.572, 95%CI = (0.359, 0.911); multivariate adjusted: OR = 0.558, 95%CI = (0.344, 0.905)]. In order to discover more potential associations, multivariate logistic regression analysis was applied and suggested that HCY and C4 were significantly correlated [age-adjusted: OR = 0.703, 95%CI = (0.519, 0.951); multivariate adjusted: OR = 0.696, 95%CI = (0.509, 0.951)]. In addition, immunoglobulin M (IgM) may influence the HCY level to some extent [unadjusted: OR = 1.427, 95%CI = (1.052, 1.936); age-adjusted: OR = 1.446, 95%CI = (1.061, 1.970); multivariate adjusted: OR = 1.447, 95%CI = (1.062, 1.973)]. Combining our results with recent studies, we propose that C4, CRP, and IgM in serum are significantly associated with HCY concentration. Further studies are needed on the mechanism of the interaction, especially among cardiovascular disease subjects. PMID- 26367538 TI - Spatial Localization and Binding of the Probiotic Lactobacillus farciminis to the Rat Intestinal Mucosa: Influence of Chronic Stress. AB - The present study aimed at detecting the exogenously applied probiotic Lactobacillus farciminis in rats, after exposure to IBS-like chronic stress, based on 4-day Water Avoidance Stress (WAS). The presence of L. farciminis in both ileal and colonic mucosal tissues was demonstrated by FISH and qPCR, with ileum as the preferential niche, as for the SFB population. A different spatial distribution of the probiotic was observed: in the ileum, bacteria were organized in micro-colonies more or less close to the epithelium whereas, in the colon, they were mainly visualized far away from the epithelium. When rats were submitted to WAS, the L. farciminis population substantially decreased in both intestinal regions, due to a stress-induced increase in colonic motility and defecation, rather than a modification of bacterial binding to the intestinal mucin Muc2. PMID- 26367539 TI - New Synthetic Routes to Triazolo-benzodiazepine Analogues: Expanding the Scope of the Bump-and-Hole Approach for Selective Bromo and Extra-Terminal (BET) Bromodomain Inhibition. AB - We describe new synthetic routes developed toward a range of substituted analogues of bromo and extra-terminal (BET) bromodomain inhibitors I-BET762/JQ1 based on the triazolo-benzodiazepine scaffold. These new routes allow for the derivatization of the methoxyphenyl and chlorophenyl rings, in addition to the diazepine ternary center and the side chain methylene moiety. Substitution at the level of the side chain methylene afforded compounds targeting specifically and potently engineered BET bromodomains designed as part of a bump and hole approach. We further demonstrate that marked selectivity for the second over the first bromodomain can be achieved with an indole derivative that exploits differential interaction with an aspartate/histidine conservative substitution on the BC loop of BET bromodomains. PMID- 26367540 TI - Quorum-Sensing Kinetics in Saccharomyces cerevisiae: A Symphony of ARO Genes and Aromatic Alcohols. AB - The kinetics of quorum sensing in Saccharomyces cerevisiae were studied using a mini-fermentation platform. The quorum-sensing molecules were monitored using our previous HPLC approach that is here supported by quantitative real-time PCR analysis of the quorum-sensing genes. We thus initially confirm correlations between peak production rates of the monitored quorum-sensing molecules 2 phenylethanol, tryptophol, and tyrosol and peak expression of the genes responsible for their synthesis: ARO8, ARO9, and ARO10. This confirms the accuracy of our previously implemented kinetic model, thus favoring its use in further studies in this field. We also show that the quorum-sensing kinetics are precisely dependent on the population growth phase and that tyrosol production is also regulated by cell concentration, which has not been reported previously. Additionally, we show that during wine fermentation, ethanol stress reduces the production of 2-phenylethanol, tryptophol, and tyrosol, which opens new challenges in the control of wine fermentation. PMID- 26367541 TI - Rapid warming and drought negatively impact population size and reproductive dynamics of an avian predator in the arid southwest. AB - Avian communities of arid ecosystems may be particularly vulnerable to global climate change due to the magnitude of projected change for desert regions and the inherent challenges for species residing in resource limited ecosystems. How arid-zone birds will be affected by rapid increases in air temperature and increased drought frequency and severity is poorly understood because avian responses to climate change have primarily been studied in the relatively mesic northern temperate regions. We studied the effects of increasing air temperature and aridity on a Burrowing Owl (Athene cunicularia) population in the southwestern United States from 1998 to 2013. Over 16 years, the breeding population declined 98.1%, from 52 pairs to 1 pair, and nest success and fledgling output also declined significantly. These trends were strongly associated with the combined effects of decreased precipitation and increased air temperature. Arrival on the breeding grounds, pair formation, nest initiation, and hatch dates all showed significant delays ranging from 9.4 to 25.1 days over 9 years, which have negative effects on reproduction. Adult and juvenile body mass decreased significantly over time, with a loss of 7.9% mass in adult males and 10.9% mass in adult females over 16 years, and a loss of 20.0% mass in nestlings over 8 years. Taken together, these population and reproductive trends have serious implications for local population persistence. The southwestern United States has been identified as a climate change hotspot, with projections of warmer temperatures, less winter precipitation, and an increase in frequency and severity of extreme events including drought and heat waves. An increasingly warm and dry climate may contribute to this species' decline and may already be a driving force of their apparent decline in the desert southwest. PMID- 26367543 TI - Assessment of Nanosecond Time Scale Motions in Native and Non-Native States of Ubiquitin. AB - The paramagnetic relaxation times of the aromatic and beta protons of Tyr59 and His68 residues of the native ubiquitin and of Tyr59 residue of the non-native ubiquitin were determined from an analysis of chemically induced dynamic nuclear polarization (CIDNP) kinetics obtained during the photoreaction of the protein and 2,2'-dipyridyl excited in the triplet state. Using the paramagnetic relaxation times determined earlier for the radicals of free amino acids as an internal standard and assuming that the hyperfine interaction (HFI) anisotropy is very similar for the radicals of free amino acids and the corresponding radicals of amino acid residues in the proteins, we determined parameters that characterize the intramolecular mobility of different protons in native and two non-native states of ubiquitin. The latter are denatured at pH 2 and 57 degrees C, and the A-state at pH 2 in a 60%/40% methanol/water mixture. The determination of the two parameters of intramolecular mobility (i.e., the correlation time of internal motion, tau(e), and the order parameter, S(2)) was only possible by analyzing paramagnetic relaxation data obtained at two magnetic fields (4.7 and 9.4 T) using nuclear magnetic resonance (NMR) spectrometry. Intramolecular correlation times fall into the submicrosecond-microsecond time scale. Longer correlation times and higher order parameters were found for the less accessible Tyr59 residue than for the His68 residue, as well as for the more buried beta protons than for the aromatic protons for both of the protein residues in the native state. For Tyr59, intramolecular mobility increases following the loss of the tertiary structure of ubiquitin. These findings strongly support the reliability of the obtained data. PMID- 26367542 TI - Devising a Consensus Framework for Validation of Novel Human Coding Loci. AB - A report on the Wellcome Trust retreat on devising a consensus framework for the validation of novel human protein coding loci, held in Hinxton, U.K., May 11-13, 2015. PMID- 26367544 TI - Observation of large group index enhancement in Doppler-broadened rubidium vapor. AB - We report experimental observation of large group index across the Lamb dips of ground hyperfine states in Doppler-broadened 87Rb vapor. By sweeping the laser frequency through each hyperfine transition we measure the saturated absorption and optical phase shift using a phase-locked Mach-Zehnder interferometer. Our measurements provide a direct demonstration of the theoretical prediction by Agarwal et al. [G. S. Agarwal and T. N. Dey, Phys. Rev. A 68, 063816, (2003)] for the first time. An enhancement factor as large as 1005 in group index was observed for Rb vapor at temperature of 85 degrees C. The experimental data are in good agreement with the theory. PMID- 26367545 TI - Fully vectorial laser resonator modeling of continuous-wave solid-state lasers including rate equations, thermal lensing and stress-induced birefringence. AB - The computer-aided design of high quality mono-mode, continuous-wave solid-state lasers requires fast, flexible and accurate simulation algorithms. Therefore in this work a model for the calculation of the transversal dominant mode structure is introduced. It is based on the generalization of the scalar Fox and Li algorithm to a fully-vectorial light representation. To provide a flexible modeling concept of different resonator geometries containing various optical elements, rigorous and approximative solutions of Maxwell's equations are combined in different subdomains of the resonator. This approach allows the simulation of plenty of different passive intracavity components as well as active media. For the numerically efficient simulation of nonlinear gain, thermal lensing and stress-induced birefringence effects in solid-state active crystals a semi-analytical vectorial beam propagation method is discussed in detail. As a numerical example the beam quality and output power of a flash-lamp-pumped Nd:YAG laser are improved. To that end we compensate the influence of stress-induced birefringence and thermal lensing by an aspherical mirror and a 90 degrees quartz polarization rotator. PMID- 26367546 TI - Diffraction-dependent spin splitting in spin Hall effect of light on reflection. AB - We report on a diffraction-dependent spin splitting of the paraxial Gaussian light beams on reflection theoretically and experimentally. In the case of horizontal incident polarization, the spin splitting is proportional to the diffraction length of light beams near the Brewster angle. However, the spin splitting is nearly independent with the diffraction length for the vertical incident polarization. By means of the angular spectrum theory, we find that the diffraction-dependent spin splitting is attributed to the first order expansion term of the reflection coefficients with respect to the transverse wave-vector which is closely related to the diffraction length. PMID- 26367547 TI - Low threshold simultaneous multi-wavelength amplified spontaneous emission modulated by the lithium fluoride/Ag layers. AB - This paper describes a multi-wavelength amplified spontaneous emission (ASE) with multilayer stacked active planar waveguides. A modulating layer of Ag is applied to make a good confinement of ASE in one active layer, while a lithium fluoride layer is inserted between the active layer and the modulating layer to avoid fluorescence quenching and confine the pump energy in one waveguide. Under optical pumping, ASE at 503 and 662 nm corresponding to the respective active layer are simultaneously observed, with extremely low thresholds at ~37.2 and ~39.7 KW/cm2. PMID- 26367548 TI - Dynamics of noise-like pulsing at sub-ns scale in a passively mode-locked fiber laser. AB - We report an original noise-like pulse dynamics observed in a figure-eight fiber laser, in which fragments are continually released from a main waveform that circulates in the cavity. Particularly, we report two representative cases of the dynamics: in the first case the released fragments drift away from the main bunch and decay over a fraction of the round-trip time, and then vanish suddenly; in the second case, the sub-packets drift without decaying over the complete cavity round-trip time, until they eventually merge again with the main waveform. The most intriguing result is that these fragments, as well as the main waveform, are formed of units with sub-ns duration and roughly the same energy. PMID- 26367549 TI - Generation of photon-number squeezed states with a fiber-optic symmetric interferometer. AB - We numerically and experimentally demonstrate photon-number squeezed state generation with a symmetric fiber interferometer in an 800-nm wavelength and compared with an asymmetric fiber interferometer, although photon-number squeezed pulses have been generated only with asymmetric interferometers. Even though we obtain -1.0dB squeezing with an asymmetric fiber interferometer, since perfect spectral phase and intensity matching between displacement and signal pulses are achieved with a symmetric fiber interferometer, we obtain better squeezing of 3.1dB. We also numerically calculate and clarify this scheme's usefulness at a 1.55-MUm wavelength. PMID- 26367550 TI - Graphene/h-BN/ZnO van der Waals tunneling heterostructure based ultraviolet photodetector. AB - We report a novel ultraviolet photodetector based on graphene/h-BN/ZnO van der Waals heterostructure. Graphene/ZnO heterostructure shows poor rectification behavior and almost no photoresponse. In comparison, graphene/h-BN/ZnO structure shows improved electrical rectified behavior and surprising high UV photoresponse (1350AW(-1)), which is two or three orders magnitude larger than reported GaN UV photodetector (0.2~20AW(-1)). Such high photoresponse mainly originates from the introduction of ultrathin two-dimensional (2D) insulating h-BN layer, which behaves as the tunneling layer for holes produced in ZnO and the blocking layer for holes in graphene. The graphene/h-BN/ZnO heterostructure should be a novel and representative 2D heterostructure for improving the performance of 2D materials/Semiconductor heterostructure based optoelectronic devices. PMID- 26367551 TI - Modeling of reflection-type laser-driven white lighting considering phosphor particles and surface topography. AB - This paper presents a model of blue laser diode (LD)-based white lighting coupled with a yellow YAG phosphor, for use in the proper design and fabrication of phosphor in automotive headlamps. First, the sample consisted of an LD, collecting lens, and phosphor was prepared that matches the model. The light distribution of the LD and the phosphor were modeled to investigate an effect of the surface topography and phosphor particle properties on the laser-driven white lighting systems by using the commercially available optical design software. Based on the proposed model, the integral spectrum distribution and the color coordinates were discussed. PMID- 26367552 TI - Holey fiber mode-selective couplers. AB - Directional mode coupling in an asymmetric holey fiber coupler is demonstrated both numerically and experimentally for the first time. The holey fiber mode couplers have interesting spectral characteristics and are also found to exhibit increased dimensional tolerances. Following a design based on numerical investigations, a dual-core polymer holey fiber coupler for LP(01) and LP(11) mode multiplexing was fabricated via a drilling and drawing technique. The measurements are compared with the simulation results. PMID- 26367553 TI - Vanishing feature constraints calibration method for binocular vision sensor. AB - Based on analyzing the measurement model of binocular vision sensor, we proposed a new flexible calibration method for binocular vision sensor using a planar target with several parallel lines. It only requires the sensor to observe the planar target at a few (at least two) different orientations. Relying on vanishing feature constraints and spacing constraints of parallel lines, linear method and nonlinear optimization are combined to estimate the structure parameters of binocular vision sensor. Linear method achieves the separation of the rotation matrix and translation vector which reduces the complexity of computation; Nonlinear algorithm ensures the calibration results for the global optimization. Towards the factors that affect the accuracy of the calibration, theoretical analysis and computer simulation are carried out respectively consequence in qualitative analysis and quantitative result. Real data shows that the accuracy of the proposed calibration method is about 0.040mm with the working distance of 800mm and the view field of 300 * 300mm. The comparison with Bougust toolbox and the method based on known length indicates that the proposed calibration method is precise and is efficient and convenient as its simple calculation and easy operation, especially for onsite calibration and self calibration. PMID- 26367554 TI - Multiplexing of fiber-optic ultrasound sensors via swept frequency interferometry. AB - The use of fiber-optic sensors for ultrasound (US) detection has many advantages over conventional piezoelectric detectors. However, the issue of multiplexing remains a major challenge. Here, a novel approach for multiplexing fiber-optic based US sensors using swept frequency interferometry is introduced. Light from a coherent swept source propagates in an all-fiber interferometric network made of a reference arm and a parallel connection of N sensing arms. Each sensing arm comprises a short polyimide coated sensing section (~4cm), which is exposed to the US excitation, preceded by a delay of different length. When the instantaneous frequency of the laser is linearly swept, the receiver output contains N harmonic beat components which correspond to the various optical paths. Exposing the sensing sections to US excitation introduces phase modulation of the harmonic components. The US-induced signals can be separated in the frequency domain and be extracted from their carriers by common demodulation techniques. The method was demonstrated by multiplexing 4 sensing fibers and detecting microsecond US pulses which were generated by a 2.25MHz ultrasound transducer. The pulses were successfully measured by all sensing fibers without noticeable cross-talk. PMID- 26367555 TI - Operation bandwidth optimization of photonic differentiators. AB - We theoretically investigate the operation bandwidth limitation of the photonic differentiator including the upper limitation, which is restrained by the device operation bandwidth and the lower limitation, which is restrained by the energy efficiency (EE) and detecting noise level. Taking the silicon photonic crystal L3 nano-cavity (PCN) as an example, for the first time, we experimentally demonstrate that the lower limitation of the operation bandwidth does exist and differentiators with different bandwidths have significantly different acceptable pulse width range of input signals, which are consistent to the theoretical prediction. Furthermore, we put forward a novel photonic differentiator scheme employing cascaded PCNs with different Q factors, which is likely to expand the operation bandwidth range of photonic differentiator dramatically. PMID- 26367556 TI - Visible electroluminescence from a ZnO nanowires/p-GaN heterojunction light emitting diode. AB - In the current paper we apply catalyst assisted vapour phase growth technique to grow ZnO nanowires (ZnO nws) on p-GaN thin film obtaining EL emission in reverse bias regime. ZnO based LED represents a promising alternative to III-nitride LEDs, as in free devices: the potential is in near-UV emission and visible emission. For ZnO, the use of nanowires ensures good crystallinity of the ZnO, and improved light extraction from the interface when the nanowires are vertically aligned. We prepared ZnO nanowires in a tubular furnace on GaN templates and characterized the p-n ZnO nws/GaN heterojunction for LED applications. SEM microscopy was used to study the growth of nanowires and device preparation. Photoluminescence (PL) and Electroluminescence (EL) spectroscopies were used to characterize the heterojunction, showing that good quality of PL emission is observed from nanowires and visible emission from the junction can be obtained from the region near ZnO contact, starting from onset bias of 6V. PMID- 26367557 TI - Algorithms for determining the radial profile of the photoelastic coefficient in glass and polymer optical fibers. AB - We discuss two algorithms to determine the value and the radial profile of the photoelastic coefficient C in glass and polymer optical fibers. We conclude that C is constant over the fiber cross-sections, with exception of silica glass fibers containing a fluorine-doped depressed cladding. In the undoped and Ge doped parts of these silica glass fibers we find a consistent value for C that is slightly larger than in bulk silica. In the fluorine-doped trenches of the absolute value of C decreases with about 27%. In polymethyl methacrylate optical fibers, the value of C significantly varies from fiber to fiber. PMID- 26367558 TI - Vulnerability to ciphertext-only attack of optical encryption scheme based on double random phase encoding. AB - We demonstrate in this paper that the traditional double random phase encoding (DRPE) technique is vulnerable to ciphertext-only attack (COA). In this method, an unauthorized user (or say attacker) is assumed to be able to retrieve the corresponding plaintext from the only ciphertext under some certain condition. The proposed scheme mainly relies on a hybrid iterative phase retrieval (HIPR) algorithm, which combines various phase retrieval algorithms. With an estimation of the number of nonzero pixels (NNP) in the original plaintext, an attacker could recover the plaintext in a large extent. The simulation results show that this method is feasible and validate. PMID- 26367559 TI - Manipulation of structural color reflection in graphene oxide dispersions using electric fields. AB - Aqueous graphene oxide (GO) dispersions with a photonic crystal structure are carefully prepared to produce structural color reflection. We fabricate a simple reflective GO cell with a unique electrode design and demonstrate that the resulting structural color reflection is electrically erasable and rewritable. GO concentration and the direction of the electric field are vital factors in the development of the device. The resulting device works well, although it exhibits a rather slow response time; in particular, the spontaneous recovery time from dark to bright color reflection requires tens of minutes. Through the application of a horizontal electric field parallel to the substrate, the recovery time can be improved, resulting in a recovery period of 3 min. Although many unsolved issues remain, the findings in GO dispersion may provide a new possibility for color filter-less bi-stable color displays with low power consumption. PMID- 26367560 TI - Efficient manipulation of graphene absorption by a simple dielectric cylinder. AB - We theoretically study the absorption property of graphene manipulated by a dielectric cylinder through an analytical method. The distinctive absorption properties of incident waves with different polarizations (TM and TE) are analyzed and they are strongly correlated with the structure resonance and material dispersion. Besides, the characteristics of graphene absorption tuned by the cylinder radius and refractive index as well as the chemical potential of graphene are systematically investigated. It is found that enhancement and continuous tunability of graphene absorption can be achieved by utilizing the whispering gallery mode produced in the dielectric cylinder and harnessing the graphene optical conductivity via tuning its chemical potential by exterior electrical grating. The theoretical studies open up a simple while efficient means to manipulate the absorption of graphene in a broad frequency range via the geometric and physical configuration of hybrid graphene-microstructures. PMID- 26367561 TI - Coherent transceiver operating at 61-Gbaud/s. AB - We use 85-Gs/s digital-to-analog convertor (DAC), 85Gs/s analog-to-digital convertor (ADC), commercial optoelectronic (OE) components with an overall electronic 3dB-bandwidth of less than 15GHz, and novel digital signal processing (DSP) algorithms implemented in CMOS to realize real time coherent transceiver operation at a record baud rate of 61-Gbaud/s. Novel DSP approaches for mitigating narrow filtering effect is critical to acquire data clock, and to improve modem performance. With transmitter pre-emphasis, novel timing recovery, and soft output maximum likelihood sequence estimation (MLSE), we are able to achieve error free operation of single carrier 200-Gbit/s polarization division multiplexed quadrature phase shift keying (PDM-QPSK) after forward error correction (FEC) at 15.2dB OSNR with pre-FEC error rate of 1.4E-2, and single carrier 400-Gbit/s PDM 16-ary quadrature amplitude modulation (16QAM) after FEC at 30.2dB OSNR with pre-FEC error rate of 9.5E-3. Error free transmission for 200 Gbit/s PDM-QPSK and 400-Gbit/s PDM-16QAM was achieved after 1200km propagation with 6dB link margin and 80km propagation respectively. PMID- 26367562 TI - Common-path diffraction optical tomography for investigation of three-dimensional structures and dynamics of biological cells: erratum. AB - An erratum is presented to correct a typographical error on Fig. 1 in [Opt. Express 22(9), 10398 (2014)]. PMID- 26367563 TI - Vulnerability of OFDR-based distributed sensors to high gamma-ray doses. AB - Vulnerability of Optical Frequency Domain Reflectometry (OFDR) based sensors to high gamma-ray doses (up to 10 MGy) is evaluated with a specific issue of a radiation-hardened temperature and strain monitoring system for nuclear industry. For this, we characterize the main radiation effects that are expected to degrade the sensor performances in such applicative domain: the radiation-induced attenuation (RIA), the possible evolution with the dose of the Rayleigh scattering phenomenon as well as its dependence on temperature and strain. This preliminary investigation is done after the irradiation and for five different optical fiber types covering the range from radiation-hardened fibers to highly radiation sensitive ones. Our results show that at these high dose levels the scattering mechanism at the basis of the used technique for the monitoring is unaffected (changes below 5%), authorizing acceptable precision on the temperature or strain measurements. RIA has to be considered as it limits the sensing range. From our vulnerability study, the OFDR sensors appear as promising candidates for nuclear industry even at doses as high as 10 MGy. PMID- 26367564 TI - Ultra-selective flexible add and drop multiplexer using rectangular optical filters based on stimulated Brillouin scattering. AB - We demonstrate an ultra-selective flexible reconfigurable add and drop multiplexer (ROADM) structure enablingseparation and aggregation operations for multi-band orthogonal frequency division multiplexing(MB-OFDM) signal with ~2-GHz spectral granularity and 300-MHz guard band. The ROADM employs rectangular optical filters based on stimulated Brillouin effect (SBS) in fiber, which have steepedges, ~1-dB passband ripple and tunable bandwidth from 100 MHz to 3 GHz realized by two different kinds of electrical feedback pump control approaches. The ROADM performance is measured with MB-OFDM signals inquadrature-phase-shift keying (QPSK) and 16-quadrature-amplitude-modulation (16-QAM) formats. For QPSK format signal, the SBS-ROADM induced penalty is ~0.7 dB while the performance for 16-QAM format is also acceptable. PMID- 26367565 TI - Perspective on resonances of metamaterials. AB - Electromagnetic resonance as the most important characteristic of metamaterials enables lots of exotic phenomena, such as invisible, negative refraction, man made magnetism, etc. Conventional LC-resonance circuit model as the most authoritative and classic model is good at explaining and predicting the fundamental resonance wavelength of a metamaterial, while feels hard for high order resonances, especially for resonance intensity (strength of resonance, determining on the performance and efficiency of metamaterial-based devices). In present work, via an easy-to-understand mass-spring model, we present a different and comprehensive insight for the resonance mechanism of metamaterials, through which both the resonance wavelengths (including the fundamental and high-order resonance wavelengths) and resonance intensities of metamaterials can be better understood. This developed theory has been well verified by different-material and different-structure resonators. This perspective will provide a broader space for exploring novel optical devices based on metamaterials (or metasurfaces). PMID- 26367566 TI - Giant cross polarization in a nanoimprinted metamaterial combining a fishnet with its Babinet complement. AB - We present a large area (1 cm2) nanoimprinted metamaterial comprising a fishnet structure and its Babinet complement, which shows giant cross polarization. When illuminated with s-polarized light, the reflected beam can be p-polarized up to 96%, depending on the azimuthal orientation of the sample. This experimental result is close to the result of numerical simulations, which predict 98.7% of cross-polarization. It is further shown, that 95-100% cross polarization is only achieved in the case when the fishnet is combined with its Babinet complement. Each structure alone (either an ordinary fishnet or a plane with metallic rectangles only) shows substantially less polarization conversion. PMID- 26367567 TI - Ultrasensitive molecular absorption detection using metal slot antenna arrays. AB - We theoretically study the transmission reduction of light passing through absorptive molecules embedded in a periodic metal slot array in a near infrared wavelength regime. From the analytically solved transmitted light, we present a simple relation given by the attenuation length of light at the resonance wavelength of the slot antennas with respect to the spectral width of the resonant transmission peak. This relation clearly explains that the control of the transmission reduction even with very low absorptive materials is possible. We investigate also the transmission reduction by absorptive molecules in a real metallic slot antenna array on a dielectric substrate and compare the results with finite difference time domain calculations. In numerical calculations, we demonstrate that the same amount of transmission reduction by a bulk absorptive material can be achieved only with one-hundredth thickness of the same material when it is embedded in an optimized Fano-resonant slot antenna array. Our relation presented in this study can contribute to label-free chemical and biological sensing as an efficient design and performance criterion for periodic slot antenna arrays. PMID- 26367568 TI - Subwavelength grating based metal-oxide nano-hair structures for optical vortex generation. AB - An all-dielectric, subwavelength grated based metal-oxide nano-hair structure for optical vortex beam generation has been presented in the paper. The nano-hair structure fabricated with alternating layers of alumina/hafnia on a fused silica substrate has a high diffraction efficiency of ~90% around the design wavelength, lambda(o) = 1.55 MUm and is insensitive to the polarization of the incident optical beam. The phase in transmission of these devices are controlled by azimuthally varying the fill fraction of the subwavelength grating. Realization of phase optical elements in an all-dielectric platform, based on subwavelength gratings offering full 0-2pi phase modulation, is important for miniaturization and integration of conventional refractive optical elements. PMID- 26367569 TI - Image quality improvement of polygon computer generated holography. AB - Quality of holographic reconstruction image is seriously affected by undesirable messy fringes in polygon-based computer generated holography. Here, several methods have been proposed to improve the image quality, including a modified encoding method based on spatial-domain Fraunhofer diffraction and a specific LED light source. Fast Fourier transform is applied to the basic element of polygon and fringe-invisible reconstruction is achieved after introducing initial random phase. Furthermore, we find that the image with satisfactory fidelity and sharp edge can be reconstructed by either a LED with moderate coherence level or a modulator with small pixel pitch. Satisfactory image quality without obvious speckle noise is observed under the illumination of bandpass-filter-aided LED. The experimental results are consistent well with the correlation analysis on the acceptable viewing angle and the coherence length of the light source. PMID- 26367570 TI - Ultrathin 90-degree sharp bends for spoof surface plasmon polaritons. AB - At low frequencies outside the plasmonic range, strongly confined surface waves can be achieved on periodically structured metal surfaces, thereby allowing for the design of compact electromagnetic guiding devices. Here, we propose an approach to realize highly efficient transmission of spoof surface plasmons around 90-degree sharp bends on ultrathin metallic films in the microwave regime. We demonstrate that by judiciously engineering the structure, the dispersion relation can be designed to reduce the scattering. Furthermore, the reflection can be suppressed by proper structural decoration at the bending corner. A one dimensional scattering theory is employed to understand and verify the transmission properties of our waveguide bend structure. Our design scheme is not restricted to the specific structure we propose here but can be applied to other guiding components built up on two dimensional metal surfaces. PMID- 26367571 TI - Evaluation of slot-to-slot coupling between dielectric slot waveguides and metal insulator-metal slot waveguides. AB - We numerically analyzed the power-coupling characteristics between a high-index contrast dielectric slot waveguide and a metal-insulator-metal (MIM) plasmonic slot waveguide as functions of structural parameters. Couplings due mainly to the transfer of evanescent components in two waveguides generated high transmission efficiencies of 62% when the slot widths of the two waveguides were the same and 73% when the waveguides were optimized by slightly different widths. The maximum transmission efficiency in the slot-to-slot coupling was about 10% higher than that in the coupling between a normal slab waveguide and an MIM waveguide. Large alignment tolerance of the slot-to-slot coupling was also proved. Moreover, a small gap inserted into the interface between two waveguides effectively enhances the transmission efficiency, as in the case of couplings between a normal slab waveguide and an MIM waveguide. In addition, couplings with very wideband transmissions over a wavelength region of a few hundred nanometers were validated. PMID- 26367572 TI - Mechanism study of 2-D laser array generation in a YAG crystal plate. AB - We have reproduced the process of two-dimensional array generation by using two crossing laser beams in a YAG crystal plate based on numerical simulation considering cross-phase modulation (XPM) and self-focusing. Furthermore, we come to the conclusion that both XPM and the cylindrical symmetry breaking in the initial beam profile contributes to the generation of two-dimensional array. In addition, we have studied the threshold input laser beam power for the two crossing beams splitting in a YAG crystal plate. Our study could be valuable in various applications, such as 2-D all-optical switching devices or multicolor pump-probe experiments. PMID- 26367573 TI - Temperature and atmosphere tunability of the nanoplasmonic resonance of a volumetric eutectic-based Bi2O3-Ag metamaterial. AB - Nanoplasmonic materials are intensively studied due to the advantages they bring in various applied fields such as photonics, optoelectronics, photovoltaics and medicine. However, their large-scale fabrication and tunability are still a challenge. One of the promising ways of combining these two is to use the self organization mechanism and after-growth engineering as annealing for tuning the properties. This paper reports the development of a bulk nanoplasmonic, Bi2O3-Ag eutectic-based metamaterial with a tunable plasmonic resonance between orange and green wavelengths. The material, obtained by a simple growth technique, exhibits a silver nanoparticle-related localized surface plasmon resonance (LSPR) in the visible wavelength range. We demonstrate the tunability of the LSPR (spectral position, width and intensity) as a function of the annealing temperature, time and the atmosphere. The critical role of the annealing atmosphere is underlined, annealing in vacuum being the most effective option for a broad control of the LSPR. The various potential mechanisms responsible for tuning the localized surface plasmon resonance upon annealing are discussed in relation to the nanostructures of the obtained materials. PMID- 26367574 TI - Resonant radiation from oscillating higher order solitons. AB - We present radiation mechanism exhibited by a higher order soliton. In a course of its evolution the higher-order soliton emits polychromatic radiation resulting in formation of multipeak frequency comb-like spectral band. The shape and spectral position of this band can be effectively controlled by the relative strength of the third order dispersion. An analytical description is corroborated by numerical simulations. It is shown that for longer pulses the described effect persists also under the action of higher order perturbations such as Raman and self-steepening. PMID- 26367575 TI - Distributed feedback GaSb based laser diodes with buried grating: a new field of single-frequency sources from 2 to 3 um for gas sensing applications. AB - We report on the growth, fabrication, experimental study and application in an absorption gas setup of distributed feed-back antimonide diode lasers with buried grating. First, half laser structures were grown by molecular beam epitaxy on GaSb substrates and stopped at the top of the waveguide. A second order Bragg grating was then defined by interferometric lithography on the top of the structure and dry etched by Reactive Ion Etching. The grating was, afterwards, buried thanks to an epitaxial regrowth of the top cladding layer. Finally, the wafer was processed using standard photolithography and wet etched into 10 um wide laser ridges. A single frequency laser emission around 2.3 um was recorded, a maximum output power of 25 mW and a total continuous tuning range reaching 4.2 nm at fixed temperature. A device has been used to detect methane gas and shows strong potential for gas spectroscopy. This process was also replicated for a target of 3 um laser emission. These devices showed an output power of 2.5 mW and a SMSR of at least 23 dB, with a 2.5 nm continuous tuning range at fixed temperature. PMID- 26367576 TI - Unbiased continuous wave terahertz photomixer emitters with dis-similar Schottky barriers. AB - We are introducing a new bias free CW terahertz photomixer emitter array. Each emitter consists of an asymmetric metal-semiconductor-metal (MSM) that is made of two side by side dis-similar Schottky contacts, on a thin layer of low temperature grown (LTG) GaAs, with barrier heights of difference (DeltaPhi(B)) and a finite lateral spacing (s). Simulations show that when an appropriately designed structure is irradiated by two coherent optical beams of different center wavelengths, whose frequency difference (?f) falls in a desired THz band, the built-in field between the two dis-similar potential barriers can accelerate the photogenerated carriers that are modulated by ?omega, making each pitch in the array to act as a CW THz emitter, effectively. We also show the permissible values of s and DeltaPhi(B) pairs, for which the strengths of the built-in electric field maxima fall below that of the critical of 50 V/MUm- i.e., the breakdown limit for the LTG-GaAs layer. Moreover, we calculate the THz radiation power per emitter in an array. Among many potential applications for these bias free THz emitters their use in endoscopic imaging without a need for hazardous external biasing circuitry that reduces the patient health risk, could be the most important one. A hybrid numerical simulation method is used to design an optimum emitter pitch, radiating at 0.5 THz. PMID- 26367577 TI - Low-complexity feed-forward carrier phase estimation for M-ary QAM based on phase search acceleration by quadratic approximation. AB - Blind phase search (BPS) algorithm for M-QAM has excellent tolerance to laser linewidth at the expense of rather high computation complexity (CC). Here, we first theoretically obtain the quadratic relationship between the test angle and corresponding distance matric during the BPS implementation. Afterwards, we propose a carrier phase estimation (CPE) based on a two-stage BPS with quadratic approximation (QA). Instead of searching the phase blindly with fixed step-size for the BPS algorithm, QA can significantly accelerate the speed of phase searching. As a result, a group factor of 2.96/3.05, 4.55/4.67 and 2.27/2.3 (in the form of multipliers/adders) reduction of CC is achieved for 16QAM, 64QAM and 256QAM, respectively, in comparison with the traditional BPS scheme. Meanwhile, a guideline for determining the summing filter block length is put forward during performance optimization. Under the condition of optimum filter block length, our proposed scheme shows similar performance as traditional BPS scheme. At 1 dB required E(S)/N(0) penalty @ BER = 10(-2), our proposed CPE scheme can tolerate a times symbol duration productDeltaf?T(S) of 1.7 * 10(-4), 6 * 10(-5) and 1.5 * 10(-5) for 16/64/256-QAM, respectively. PMID- 26367578 TI - Deterministic phase engineering for optical Fano resonances with arbitrary lineshape and frequencies. AB - We present an approach of deterministic phase engineering that can enable the rational design of optical Fano resonances with arbitrarily pre-specified lineshapes. Unlike all the approaches previously used to design optical Fano resonances, which fall short of designing the resonances with arbitrary lineshapes because of the lack of information for the optical phases involved, we develop our approach by capitalizing on unambiguous knowledge for the phase of optical modes. Optical Fano resonances arise from the interference of photons interacting with two optical modes with substantially different quality factors. We find that the phase difference of the two modes involved in optical Fano resonances is determined by the eigenfrequency difference of the modes. This allows us to deterministically engineer the phase by tuning the eigenfrequency, which may be very straightforward. We use dielectric grating structures as an example to illustrate the notion of deterministic engineering for the design of optical Fano resonances with arbitrarily pre-specified symmetry, linewidth, and wavelengths. PMID- 26367579 TI - Jitter reduction technique for acoustic radiation force impulse microscopy via photoacoustic detection. AB - We demonstrate a jitter noise reduction technique for acoustic radiation force impulse microscopy via photoacoustic detection (PA-ARFI), which promises to be capable of measuring cell mechanics. To reduce the jitter noise induced by Q switched pulsed laser operated at high repetition frequency, photoacoustic signals from the surface of an ultrasound transducer are aligned by cross correlation and peak-to-peak detection, respectively. Each method is then employed to measure the displacements of a target sample in an agar phantom and a breast cancer cell due to ARFI application, followed by the quantitative comparison between their performances. The suggested methods for PA-ARFI significantly reduce jitter noises, thus allowing us to measure displacements of a target cell due to ARFI application by less than 3 MUm. PMID- 26367581 TI - Ultrafast, low-power, all-optical switching via birefringent phase-matched transverse mode conversion in integrated waveguides. AB - We demonstrate the potential of birefringence-based, all-optical, ultrafast conversion between the transverse modes in integrated optical waveguides by modelling the conversion process by numerically solving the multi-mode coupled nonlinear Schroedinger equations. The observed conversion is induced by a control beam and due to the Kerr effect, resulting in a transient index grating which coherently scatters probe light from one transverse waveguide mode into another. We introduce birefringent phase matching to enable efficient all-optically induced mode conversion at different wavelengths of the control and probe beam. It is shown that tailoring the waveguide geometry can be exploited to explicitly minimize intermodal group delay as well as to maximize the nonlinear coefficient, under the constraint of a phase matching condition. The waveguide geometries investigated here, allow for mode conversion with over two orders of magnitude reduced control pulse energy compared to previous schemes and thereby promise nonlinear mode switching exceeding efficiencies of 90% at switching energies below 1 nJ. PMID- 26367580 TI - Aspheric subaperture stitching based on system modeling. AB - Instead of various mathematical stitching algorithms, an aspheric subaperture stitching interferometric method relying on modern computer modeling technique is presented. Based on our previously reported non-null annular subaperture stitching interferometry (NASSI), a simultaneous reverse optimizing reconstruction (SROR) method based on system modeling is proposed for full aperture figure error reconstruction. All the subaperture measurements are simulated simultaneously with a multi-configuration model in a ray tracing program. With the multi-configuration model, full aperture figure error would be extracted in form of Zernike polynomials from subapertures wavefront data by the SROR method. This method concurrently accomplishes subaperture retrace error and misalignment correction, requiring neither complex mathematical algorithms nor subaperture overlaps. Experiment results showing the validity of SROR method are presented. PMID- 26367582 TI - 112 Gb/s transmission with a directly-modulated laser using FFT-based synthesis of orthogonal PAM and DMT signals. AB - We report the experimental measurement of 112 Gb/s transmission back-to-back and through 12 km of S-SMF with a single directly-modulated laser (DML) using the novel modulation format Orthogonal PAM-DMT. This work demonstrates a record DML based 112 Gb/s receiver sensitivity of -7.1 dBm at a BER of 10(-3), outperforming conventional PAM and DMT by approximately 2.5 dB. PMID- 26367583 TI - Modeling "wiggling" as a multi-path interference problem in AMCW ToF imaging. AB - Amplitude modulated continuous wave time-of-flight range cameras suffer from an inherent depth measurement error due to aliasing of the emitted signal vs reference signal correlation function. This is due to higher harmonics present in both signals which are not accounted for in the model or measurements. This "wiggling" error is generally corrected by employing a correction function based on frequency and depth dependent calibration data. This problem is shown to be equivalent to a multi-path interference problem. Casting the problem into the multi-path interference domain and utilizing multiple modulation frequencies provides tools for dealing with the depth error without calibration in a frequency independent way. PMID- 26367584 TI - Photobleaching effect in bismuth-doped germanosilicate fibers. AB - Photoinduced reduction of absorption (photobleaching) in bismuth-doped germanosilicate fibers irradiated with 532-nm laser has been observed for the first time. It was demonstrated that bismuth-related active centers having the absorption bands at wavelengths of 1400 and 1700 nm degrade under photoexcitation at 532 nm. The photobleaching process rate was estimated using conventional stretched exponential technique. It was found that the photobleaching rate in bismuth-doped germanosilicate fibers does not depend on type of bismuth-related active center. The possible underlying mechanism of photobleaching process in bismuth-doped fibers is discussed. PMID- 26367585 TI - Spatiotemporal coupled-mode theory of guided-mode resonant gratings. AB - In this paper, we develop spatiotemporal coupled-mode theory to describe optical properties of guided-mode resonant gratings. We derive partial differential equations that describe both spatial and temporal evolution of the field inside the grating. These equations describe the coupling of two counter-propagating grating modes, revealing the structure's "dark" and "bright" resonances at normal incidence of light. Moreover, the proposed theory allows us to obtain a simple approximation of the transmission and reflection coefficients taking into account both light's frequency and angle of incidence. This approximation can be considered as the generalization of the Fano line-shape. The approximation is in good agreement with the rigorous computations based on the Fourier modal method. The results of the paper will be useful for design and analysis of guided-mode resonant filters and other photonic devices. PMID- 26367586 TI - Fourier-based interpolation bias prediction in digital image correlation. AB - Based on the Fourier method, this paper deduces analytic formulae for interpolation bias in digital image correlation, explains the well-known sinusoidal-shaped curves of interpolation bias, and introduces the concept of interpolation bias kernel, which characterizes the frequency response of the interpolation bias and thus provides a measure of the subset matching quality of the interpolation algorithm. The interpolation bias kernel attributes the interpolation bias to aliasing effect of interpolation and indicates that high frequency components are the major source of interpolation bias. Based on our theoretical results, a simple and effective interpolation bias prediction approach, which exploits the speckle spectrum and the interpolation transfer function, is proposed. Significant acceleration is attained, the effect of subset size is analyzed, and both numerical simulations and experimental results are found to agree with theoretical predictions. During the experiment, a novel experimental translation technique was developed that implements subpixel translation of a captured image through integer pixel translation on a computer screen. Owing to this remarkable technique, the influences of mechanical error and out-of-plane motion are eliminated, and complete interpolation bias curves as accurate as 0.01 pixel are attained by subpixel translation experiments. PMID- 26367587 TI - 300 nm bandwidth adiabatic SOI polarization splitter-rotators exploiting continuous symmetry breaking. AB - Adiabatic polarization splitter-rotators are investigated exploiting continuous symmetry breaking thereby achieving significant device size and losses reduction in a single mask fabrication process for both SOI channel and ridge waveguides. A crosstalk lower than -25 dB is expected over 300nm bandwidth, making the device suitable for full grid CWDM and diplexer/triplexer FTTH applications at 1310, 1490 and 1550nm. PMID- 26367588 TI - Analysis and simulation of entirely saturated unilateral laser spot tails in BCCD. AB - A new phenomenon involving the entire saturation of unilateral tails of buried channel charge-coupled devices (BCCDs) under laser radiation is observed in this study. A physical model related to this phenomenon is constructed based on the assumption that the charge transfer inefficiency of BCCD is a jump function of signal charge quantity. The profile of a spot tail under laser radiation is simulated using this self-developed model. The simulation results are compared with experimental findings to validate this model. PMID- 26367589 TI - Tailoring the performances of low operating voltage InAlAs/InGaAs avalanche photodetectors. AB - We present tailoring of the performances of thin multiplication layer InAlAs/InGaAs avalanche photodetectors (APDs) with operating voltages lower than 20 V. Their operating voltages, gain-voltage slopes and dark currents were successfully tailored by changing the electric field distributions in avalanche region. The thin multiplication layer APDs show small activation energies of the dark current ranging from 0.12 to 0.19 eV at temperatures above 220 K, suggesting a band-trap-band tunneling dominant dark current mechanism over this temperature range. The dark currents show very weak temperature dependences at temperatures lower than 175 K, which mainly originate from the band-to-band tunneling and the surface leakage currents. The spectral responsivity of those APDs show anomalous negative temperature coefficients at gain factors larger than 1, which is attributed to the enhanced phonon scattering effect of carriers in the avalanche region at higher temperatures. Good gain factor uniformity at a given bias is observed for those APDs, and the charge layer is found to help improve the gain uniformity. PMID- 26367590 TI - Propagation of sharply autofocused ring Airy Gaussian vortex beams. AB - Controlling the focal length and the intensity of the optical focus in the media is an important task. Here we investigate the propagation properties of the sharply autofocused ring Airy Gaussian vortex beams numerically and some numerical experiments are performed. We introduce the distribution factor b into the initial beams, and discuss the influences for the beams. With controlling the factor b, the beams that tend to a ring Airy vortex beam with the smaller value, or a hollow Gaussian vortex beam with the larger one. By a choice of initial launch condition, we find that the number of topological charge of the incident beams, as well as its size, greatly affect the focal intensity and the focal length of the autofocused ring Airy Gaussian vortex beams. Furthermore, we show that the off-axis autofocused ring Airy Gaussian beams with vortex pairs can be implemented. PMID- 26367591 TI - Bionic research of pit vipers on infrared imaging. AB - The members of viperidae crotalinae (pit viper) family have special pit organs to detect infrared radiation in normal room conditions, whereas most artificial uncooled infrared focal plane arrays (FPAs) operate only in a vacuum chamber. Dissection shows that the pit membrane is a unique substrate-free structure. The temperature rise advantage of this pit organ was verified in comparison with an assumed substrate pit organ (as an artificial FPA structure). Inspired by the pit viper, we introduced this structure to infrared FPA, replacing the conventional substrate FPA. The substrate-free FPA was fabricated by micro-elctromechanical systems (MEMS) process and placed into an infrared imaging system to obtain thermal images of the human body in atmosphere and vacuum working conditions. We show that the infrared capability of the substrate-free pit organ was achieved. PMID- 26367592 TI - Entanglement measurement of a coupled silicon microring photon pair source. AB - Using two-photon (Franson) interferometry, we measure the entanglement of photon pairs generated from an optically-pumped silicon photonic device consisting of a few coupled microring resonators. The pair-source chip operates at room temperature, and the InGaAs single-photon avalanche detectors (SPADs) are thermo electrically cooled to 234K. Such a device can be integrated with other components for practical entangled photon-pair generation at telecommunications wavelengths. PMID- 26367593 TI - Simultaneous retrieval of the complex refractive index and particle size distribution. AB - A secondary optimization technique is proposed that allows the complex refractive index and particle size distribution (PSD) to be retrieved simultaneously by using the diffuse transmittance (T), diffuse reflectance (R), and collimated transmittance (T(c)) of a 1-D spherical particle systems as measured values. In the proposed method, two 1-D experimental samples of different thicknesses were exposed to continuous wave lasers of two different wavelengths. First, T, R, and T(c) were calculated by solving the radiative transfer equation. Then, the complex refractive index and PSDs were retrieved simultaneously by applying the inversion technique, quantum particle swarm optimization. However, the estimated results of the PSDs proved to be inaccurate. Hence, a secondary optimization was performed to improve the accuracy of the PSDs on the basis of the first optimization process. The results showed that the proposed technique can estimate the complex refractive index and particle size distribution accurately. PMID- 26367594 TI - Tuning the quality factor of split nanobeam cavity by nanoelectromechanical systems. AB - A split nanobeam cavity is theoretically designed and experimentally demonstrated. Compared with the traditional photonic crystal nanobeam cavities, it has an air-slot in its center. Through the longitudinal and lateral movement of half part of the cavity, the resonance wavelength and quality factor are tuned. Instead of achieving a cavity with a large tunable wavelength range, the proposed split nanobeam cavity demonstrates a considerable quality factor change but the resonance wavelength is hardly varied. Using a nanoelectromechanical system (NEMS) comb-drive actuator to control the longitudinal and lateral movement of the split nanobeam cavity, the experimentally-measured change of quality factor agrees well with the simulated value. Meanwhile, the variation range of resonance wavelength is smaller than the full width at half maximum of the resonance. The proposed structure may have potential application in Q switched lasers. PMID- 26367595 TI - Pulse front adaptive optics: a new method for control of ultrashort laser pulses. AB - Ultrafast lasers enable a wide range of physics research and the manipulation of short pulses is a critical part of the ultrafast tool kit. Current methods of laser pulse shaping are usually considered separately in either the spatial or the temporal domain, but laser pulses are complex entities existing in four dimensions, so full freedom of manipulation requires advanced forms of spatiotemporal control. We demonstrate through a combination of adaptable diffractive and reflective optical elements - a liquid crystal spatial light modulator (SLM) and a deformable mirror (DM) - decoupled spatial control over the pulse front (temporal group delay) and phase front of an ultra-short pulse was enabled. Pulse front modulation was confirmed through autocorrelation measurements. This new adaptive optics technique, for the first time enabling in principle arbitrary shaping of the pulse front, promises to offer a further level of control for ultrafast lasers. PMID- 26367596 TI - Full loss compensation in hybrid plasmonic waveguides under electrical pumping. AB - Surface plasmon polaritons (SPPs) give an opportunity to break the diffraction limit and design nanoscale optical components, however their practical implementation is hindered by high ohmic losses in a metal. Here, we propose a novel approach for efficient SPP amplification under electrical pumping in a deep subwavelength metal-insulator-semiconductor waveguiding geometry and numerically demonstrate full compensation for the SPP propagation losses in the infrared at an exceptionally low pump current density of 0.8 kA/cm2. This value is an order of magnitude lower than in the previous studies owing to the thin insulator layer between a metal and a semiconductor, which allows injection of minority carriers and blocks majority carriers reducing the leakage current to nearly zero. The presented results provide insight into lossless SPP guiding and development of future high dense nanophotonic and optoelectronic circuits. PMID- 26367597 TI - Offset-free broadband Yb:fiber optical frequency comb for optical clocks. AB - We demonstrate a passively offset-frequency stabilized optical frequency comb centered at 1060 nm. The offset-free comb was achieved through difference frequency generation (DFG) between two portions of a supercontinuum based on a Yb:fiber laser. As the DFG comb had only one degree of freedom, repetition frequency, full stabilization was achieved via locking one of the modes to an ultra-stable continuous wave (CW) laser. The DFG comb provided sufficient average power to enable further amplification, using Yb-doped fiber amplifier, and spectral broadening. The spectrum spanned from 690 nm to 1300 nm and the average power was of several hundred mW, which could be ideal for the comparison of optical clocks, such as optical lattice clocks operated with Sr (698 nm) and Hg (1063 nm) reference atoms. PMID- 26367599 TI - Opto-mechanical artificial eye with accommodative ability. AB - The purpose of this study was to describe the design and characterization of a new opto-mechanical artificial eye (OMAE) with accommodative ability. The OMAE design is based on a second-pass configuration where a small source of light is used at the artificial retina plane. A lens whose focal length can be changed electronically was used to add the accommodation capability. The changes in the OMAE's aberrations with the lens focal length, which effectively changes the accommodative state of the OMAE, were measured with a commercial aberrometer. Changes in power and aberrations with room temperature were also measured. The OMAE's higher-order aberrations (HOAs) were similar to the ones of the human eye, including the rate at which fourth-order spherical aberration decreased with accommodation. The OMAE design proposed here is simple, and it can be implemented in an optical system to mimic the optics of the human eye. PMID- 26367598 TI - Saturation of 640-nm absorption in Cr4+:YAG for an InGaN laser diode pumped passively Q-switched Pr3+:YLF laser. AB - We measure the absorption recovery time, the ground- and excited-state absorption cross sections of a Cr4+:YAG crystal at 640 nm for the first time. A pump-probe measurement reveals the existence of two recovery times of 26 ns and 5.6 MUs. By a Z-scan experiment, the ground- and excited-state absorption cross sections are estimated to be 1.70 - 1.75 * 10(-17) and 0.95 - 1.00 * 10(-17)cm2, respectively. The adequacy of the proposed model and the accuracy of the estimated parameters of the saturable absorber are verified by reproducing the experimentally obtained performance of a passively Q-switched Pr3+:YLF laser with the Cr4+:YAG saturable absorber from rate equation analysis. PMID- 26367600 TI - Two-dimensional pseudo-random optical phased array based on tandem optical injection locking of vertical cavity surface emitting lasers. AB - We demonstrate, both theoretically and experimentally, a pseudo-random, two dimensional optical phased array (OPA) concept based on tandem injection locking of 64-element vertical cavity surface emitting laser (VCSEL) arrays. A low cavity Q VCSEL design resulted in an injection locking optical power of less than 1 MUW per VCSEL, providing large OPA scaling potential. Tandem injection locking of two VCSEL arrays resulted in measured controllable optical phase change of 0-1.6pi. A high quality beam formed with suppressed grating lobes due to the pseudo-random array design was demonstrated with performance close to simulated results. A preliminary 2.2 degrees x 1.2 degrees beam steering example using the tandem arrays was also demonstrated. PMID- 26367602 TI - Time-resolved measurement of single pulse femtosecond laser-induced periodic surface structure formation induced by a pre-fabricated surface groove. AB - Time-resolved diffraction microscopy technique has been used to observe the formation of laser-induced periodic surface structures (LIPSS) from the interaction of a single femtosecond laser pulse (pump) with a nano-scale groove mechanically formed on a single-crystal Cu substrate. The interaction dynamics (0 1200 ps) was captured by diffracting a time-delayed, frequency-doubled pulse (probe) from nascent LIPSS formation induced by the pump with an infinity conjugate microscopy setup. The LIPSS ripples are observed to form asynchronously, with the first one forming after 50 ps and others forming sequentially outward from the groove edge at larger time delays. A 1-D analytical model of electron heating including both the laser pulse and surface plasmon polariton excitation at the groove edge predicts ripple period, melt spot diameter, and qualitatively explains the asynchronous time-evolution of LIPSS formation. PMID- 26367601 TI - High precision optical cavity length and width measurements using double modulation. AB - We use doubly phase modulated light to measure both the length and the linewidth of an optical resonator with high precision. The first modulation is at RF frequencies and is set near a multiple of the free spectral range, whereas the second modulation is at audio frequencies to eliminate offset errors at DC. The light in transmission or in reflection of the optical resonator is demodulated while sweeping the RF frequency over the optical resonance. We derive expressions for the demodulated power in transmission, and show that the zero crossings of the demodulated signal in transmission serve as a precise measure of the cavity linewidth at half maximum intensity. We demonstrate the technique on two resonant cavities, with lengths 16 m and a 4 km, and achieve an absolute length accuracy as low as 70 ppb. The cavity width for the 16 m cavity was determined with an accuracy of approximately 6000 ppm. Through an analysis of the systematic errors we show that this result could be substantially improved with the reduction of technical sources of uncertainty. PMID- 26367603 TI - Photonic microwave waveforms generation based on time-domain processing. AB - A new photonic approach of microwave waveform generator based on time-domain synthesis is proposed and experimentally demonstrated, in which two single-drive Mach-Zehnder modulators biased at quadrature point are severed as optical pulse carvers and various microwave waveforms can be generated by carving and overlapping optical field envelopes. The theoretical analysis and simulation are developed. In experiment, a square waveform with 50% duty cycle, triangular waveform with full duty cycle, and sawtooth (or reversed-sawtooth) waveform with 50% duty cycle are generated. Furthermore, a frequency doubling sawtooth (or reversed-sawtooth) waveform with full duty cycle is also obtained. PMID- 26367604 TI - High-precision flow temperature imaging using ZnO thermographic phosphor tracer particles. AB - Zinc oxide (ZnO) particles are characterised as a tracer for temperature measurements in turbulent flows, in the context of the thermographic particle image velocimetry technique. Flow measurements are used to compare the temperature precision of ZnO to that obtained using a well-characterised thermographic phosphor, BAM:Eu(2+), under the same conditions. For this two colour, ratio-based technique the strongly temperature-dependent redshift of the luminescence emission of ZnO offers improved temperature sensitivity, and so at room temperature a threefold increase in the temperature precision is achieved. A dependence of the intensity ratio on the laser fluence is identified, and additional measurements with different laser pulse durations are used to independently show that there is also a dependence on the laser excitation irradiance, irrespective of fluence. A simple method to correct for these effects is demonstrated and sources of error are analysed in detail. Temperature images in a Re = 2000 jet of air heated to 363 K with a precision of 4 K (1.1%) are presented. The sensitivity of ZnO increases across the tested temperature range 300-500 K, so that at 500 K, using a seeding density of 2 x 10(11) particles/m(3), a precision of 3 K (0.6%) is feasible. This new phosphor extends the capabilities of this versatile technique toward the study of flows with small temperature variations. PMID- 26367605 TI - Unimorph deformable mirror for space telescopes: design and manufacturing. AB - Large space telescopes made of deployable and lightweight structures suffer from aberrations caused by thermal deformations, gravitational release, and alignment errors which occur during the deployment procedure. An active optics system would allow on-site correction of wave-front errors, and ease the requirements on thermal and mechanical stability of the optical train. In the course of a project funded by the European Space Agency we have developed and manufactured a unimorph deformable mirror based on piezoelectric actuation. The mirror is able to work in space environment and is designed to correct for large aberrations of low order with high surface fidelity. This paper discusses design, manufacturing and performance results of the deformable mirror. PMID- 26367606 TI - Photoemission from advanced heterostructured Al(x)Ga(1-x)As/GaAs photocathodes under multilevel built-in electric field. AB - A heterostructured Al(x)Ga(1-x)As/GaAs photocathode consisting of a composition graded buffer layer and an exponential-doped emission layer is developed to improve the photoemission performance over the wavelength region of interest. The theoretical quantum efficiency models for reflection-mode and transmission-mode Al(x)Ga(1-x)As/GaAs photocathodes are deduced based on one-dimensional continuity equations, respectively. By comparison of simulated results with conventional quantum efficiency models, it is found that the multilevel built-in electric field can effectively improve the quantum efficiency, which is related to the buffer layer parameters and cathode thicknesses. This special graded bandgap structure arising from the compositional grade in the buffer layer and doping grade in the emission layer would bring about the reduction of back interface recombination losses and the efficient collection of photons generating photoelectrons. Moreover, a best fit of the experimental quantum efficiency data can be achieved with the aid of the deduced models, which would provide an effective approach to evaluate internal parameters for the special graded bandgap photoemitters. PMID- 26367607 TI - Design of panoramic lens based on ogive and aspheric surface. AB - A new method improving the design of panoramic lens with a long focal length based on ogive and aspheric surface is proposed. In this design, we use a special conjugation between "annular entrance pupil" and aperture stop to correct the chromatic transverse aberrations. Moreover, we use a new imaging relationship to increase the Effective Focal Length (EFL) of the panoramic lens and the CCD utilization. We realize a panoramic lens with a 360 degrees * (45 degrees ~85 degrees )field of view (FOV) and a 10.375mm EFL, which is 1.54 times than the conventional imaging relationship. PMID- 26367608 TI - Kinetic and fluid dynamic modeling, numerical approaches of flowing-gas diode pumped alkali vapor amplifiers. AB - Comprehensive analysis of kinetic and fluid dynamic processes in flowing-gas diode-pumped alkali vapor amplifiers is reported. Taking into account effects of the temperature, the amplified spontaneous emission, the saturation power, the excitation of the alkali atoms to high electronic levels and the ionization, a detailed physical model is established to simulate the output performance of flowing-gas diode-pumped alkali vapor amplifiers. Influences of the flow velocity and the pump power on the amplified power are calculated and analyzed. Comparisons between single and double amplifier, longitudinal and transverse flow are made. Results show that end-pumped cascaded amplifier can provide higher output power under the same total pump power and the cell length, while output powers achieved by single- and double-end pumped, double-side pumped amplifiers with longitudinal or transverse flow have a complicated but valuable relation. Thus the model is extremely helpful for designing high-power flowing-gas diode pumped alkali vapor amplifiers. PMID- 26367609 TI - Measurements of the nonlinear refractive index in scattering media using the Scattered Light Imaging Method--SLIM. AB - The Scattered Light Imaging Method (SLIM) was applied to measure the nonlinear refractive index of scattering media. The measurements are based on the analysis of the side-view images of the laser beam propagating inside highly scattering liquid suspensions. Proof-of-principle experiments were performed with colloids containing silica nanoparticles that behave as light scatterers. The technique allows measurements with lasers operating with arbitrary repetition rate as well as in the single-shot regime. The new method shows advantages and complementarity with respect to the Z-scan technique which is not appropriate to characterize scattering media. PMID- 26367610 TI - Laser induced periodic surface structure formation in germanium by strong field mid IR laser solid interaction at oblique incidence. AB - Laser induced periodic surface structures (LIPSS or ripples) were generated on single crystal germanium after irradiation with multiple 3 um femtosecond laser pulses at a 45 degrees angle of incidence. High and low spatial frequency LIPSS (HSFL and LSFL, respectively) were observed for both s- and p-polarized light. The measured LSFL period for p-polarized light was consistent with the currently established LIPSS origination model of coupling between surface plasmon polaritons (SPP) and the incident laser pulses. A vector model of SPP coupling is introduced to explain the formation of s-polarized LSFL away from the center of the damage spot. Additionally, a new method is proposed to determine the SPP propagation length from the decay in ripple depth. This is used along with the measured LSFL period to estimate the average electron density and Drude collision time of the laser-excited surface. Finally, full-wave electromagnetic simulations are used to corroborate these results while simultaneously offering insight into the nature of LSFL formation. PMID- 26367611 TI - Broadband high efficiency asymmetric transmission of achiral metamaterials. AB - Asymmetric transmission (AT) effect has attracted great interest in recent years, due to its potential application in integrated photonics from GHz to optical frequency. To realize AT effect, numerous metamaterials have been proposed, mainly based on the chirality of the structure. In this paper, we demonstrate that achiral metamaterials can also have AT effect. Furthermore, it is shown that modal conversion is more essential than chirality to achieve AT effect. In particular, we have proposed a mirror symmetric metamaterial with broadband high efficiency AT effect for circular polarization wave operating at THz region. With further optimization of the unit cell, >80% of the central frequency bandwidth and average 74.05 (maximum150) transmission ratio can be obtained. The idea demonstrated here can also be applied to other frequency regions. PMID- 26367612 TI - DiPOLE: a 10 J, 10 Hz cryogenic gas cooled multi-slab nanosecond Yb:YAG laser. AB - The Diode Pumped Optical Laser for Experiments (DiPOLE) project at the Central Laser Facility aims to develop a scalable, efficient high pulse energy diode pumped laser amplifier system based on cryogenic gas cooled, multi-slab ceramic Yb:YAG technology. We present recent results obtained from a scaled down prototype laser system designed for operation at 10 Hz pulse repetition rate. At 140 K, the system generated 10.8 J of energy in a 10 ns pulse at 1029.5 nm when pumped by 48 J of diode energy at 940 nm, corresponding to an optical to optical conversion efficiency of 22.5%. To our knowledge, this represents the highest pulse energy obtained from a cryo cooled Yb laser to date and the highest efficiency achieved by a multi-Joule diode pumped solid state laser system. Additionally, we demonstrated shot-to-shot energy stability of 0.85% rms for the system operated at 7 J, 10 Hz during several runs lasting up to 6 hours, with more than 50 hours in total. We also demonstrated pulse shaping capability and report on beam, wavefront and focal spot quality. PMID- 26367613 TI - Angular dependence of fluorescence from turbid media. AB - We perform Monte Carlo light scattering simulations to study the angular distribution of the fluorescence emission from turbid media and compare the results to measured angular distributions from fluorescing white paper samples. The angular distribution of fluorescence emission is significantly depending on the concentration of fluorophores. The simulations show also a dependence on the angle of incidence that is however not as evident in the measurements. A detailed analysis of the factors affecting this angular distribution indicates that it is strongly correlated to the mean depth of the fluorescence process. The findings can find applications in fluorescence spectroscopy and are of particular interest when optimizing the impact of fluorescence on e.g. the appearance of paper as the measured values are angle dependent. PMID- 26367614 TI - Clarifying the origin of third-harmonic generation from film-coupled nanostripes. AB - The resonance associated with plasmonic nanostructures strongly enhances local optical fields, and can thus dramatically enhance the nonlinear response of the composite structure. However, the origin of the nonlinear signal generated from hybrid nanostructures consisting of both metallic and dielectric components can be ambiguous when all constituents possess nonlinearities. In this paper, we introduce a method for specifically identifying the third harmonic generation (THG) originating from different nonlinear sources in a film-coupled nanostripe. The nanostripe consists of a metallic patch separated from a metallic film by a dielectric spacer. By considering the THG from each nonlinear source separately, we show that the near- and far-field behaviors of the THG generated within the various constituents of the nanostripe are distinguishable due to fundamental differences in the THG radiation properties. The THG signal from the metal is shown to be suppressed by the structure itself, while the THG signal from the spacer is enhanced by the gap plasmon modes supported by the structure. The total THG signal is found to be the sum of all nonlinear sources, with the far-field radiation pattern determined by the ratio between the third-order susceptibilities of the dielectric and the metal. PMID- 26367615 TI - Dense dissimilar waveguide routing for highly efficient thermo-optic switches on silicon. AB - We analyze and demonstrate a method for increasing the efficiency of thermo-optic phase shifters on a silicon-on-insulator platform. The lack of cross-coupling between dissimilar waveguides allows highly dense waveguide routing under heating elements and a corresponding increase in efficiency. We demonstrate a device with highly dense routing of 9 waveguides under a 10 um wide heater and achieve a low switching power of 95 uW, extinction ratio greater than 20 dB, and less than 0.1 dB ripple in the through spectrum with a footprint of less than 800 um * 180 um. The increase in waveguide density is found not to negatively impact the switch response time. PMID- 26367617 TI - On-chip visible-to-infrared supercontinuum generation with more than 495 THz spectral bandwidth. AB - We report ultra-broadband supercontinuum generation in high-confinement Si3N4 integrated optical waveguides. The spectrum extends through the visible (from 470 nm) to the infrared spectral range (2130 nm) comprising a spectral bandwidth wider than 495 THz, which is the widest supercontinuum spectrum generated on a chip. PMID- 26367616 TI - Acousto-optic pulse picking scheme with carrier-frequency-to-pulse-repetition rate synchronization. AB - We introduce and experimentally validate a pulse picking technique based on a travelling-wave-type acousto-optic modulator (AOM) having the AOM carrier frequency synchronized to the repetition rate of the original pulse train. As a consequence, the phase noise characteristic of the original pulse train is largely preserved, rendering this technique suitable for applications requiring carrier-envelope phase stabilization. In a proof-of-principle experiment, the 1030-nm spectral part of an 74-MHz, carrier-envelope phase stable Ti:sapphire oscillator is amplified and reduced in pulse repetition frequency by a factor of two, maintaining an unprecedentedly low carrier-envelope phase noise spectral density of below 68 mrad. Furthermore, a comparative analysis reveals that the pulse-picking-induced additional amplitude noise is minimized, when the AOM is operated under synchronicity. The proposed scheme is particularly suitable when the down-picked repetition rate is still in the multi-MHz-range, where Pockels cells cannot be applied due to piezoelectric ringing. PMID- 26367618 TI - On the use of the supporting quadric method in the problem of the light field eikonal calculation. AB - A new iterative technique for calculating the eikonal function of a light field providing the focusing into a set of points is introduced. This technique is a modification of the supporting quadric method widely used for design of reflecting and refracting optical surfaces for generating prescribed illuminance distributions at given discrete set of points. As an example, we design a refractive optical element which focuses an incident beam into a set of points with energy pattern forming an image of a keyboard of a calculator. It is shown that the proposed technique is well-suited for the design of diffractive optical elements producing continuous intensity distributions within the scalar theory of diffraction. It is also shown that the calculated eikonal function is a good initial guess when designing diffractive optical elements using the iterative Gerchberg-Saxton algorithm. PMID- 26367619 TI - High brightness continuous wave ceramic Yb:LuAG thin-disk laser. AB - We report on a ceramic Yb:LuAG thin-disk laser in continuous wave operation. The Yb:LuAG ceramic was fabricated using solid-state reactive sintering method. In multi-mode operation in open-air, an output power of 1.74 kW with an optical-to optical efficiency of 65.0% and slope efficiency of 71.2% was obtained. In near fundamental mode operation we obtained an output power of 1.29 kW and an average beam quality factor of M2 = 1.44 with an optical-to-optical efficiency of 48.2%. The near-fundamental mode result was realized with a simple evacuated, stable resonator cavity with just the thin-disk gain medium and output coupler. To the best of the authors' knowledge, this is not only the first time more than 1 kW has been demonstrated from a ceramic Yb:LuAG medium, but this is also currently the brightest continuous wave Yb-doped ceramic laser. PMID- 26367620 TI - Comparative study of the frequency-doubling performance on ring and linear cavity at short wavelength region. AB - We theoretically and experimentally perform a comparative study on performance of the linear standing-wave cavity and ring cavity for external cavity frequency doubling at the wavelength from 795 nm to 397.5 nm. The two cavities show obvious differences of the thermal effect of nonlinear crystal, cavity sensitivity, and maximum output power. The results show that ring cavity as the external enhancement cavity is a better choice than standing-wave cavity at short wavelength region. At last, a 397.5 nm violet laser with 408 mW corresponding to an input power of 992 mW is obtained by using the ring cavity, considering the original mode-matching efficiency of 98% between the 795 nm laser and frequency doubling cavity, the conversion efficiency is 41.9%. PMID- 26367621 TI - Fiber-integrated concept to electrically tune pulsed fiber lasers based on step chirped fiber Bragg grating arrays. AB - We present a novel method to discretely tune the emission wavelength of pulsed fiber-integrated lasers. As spectral filter, a step-chirped fiber Bragg grating (FBG) array is employed combining a monolithic structure with an unrivaled design freedom enabling large tuning bandwidths as well as tailored spectral characteristics towards fingerprint tuning features. Together with an electrical control mechanism ensuring programmable operation, this tuning method promotes fiber-integrated lasers to access new fields of applications e.g. in biophotonics and distributed sensing. The potential of this tuning concept is investigated based on an Ytterbium-doped fiber laser. The system shows superb emission properties including excellent wavelength stability, high spectral signal contrast (up to 50dB) and narrow linewidth (15GHz) as well as adjustable pulse durations in the nanosecond range with peak powers up to 100W. Additionally, the unique spectral potential of this method is demonstrated by realizing filter designs enabling e.g. a record tuning range of 74nm for fiber-integrated lasers. PMID- 26367622 TI - Dynamics of nonequilibrium carrier decay in AlGaN epitaxial layers with high aluminum content. AB - Carrier dynamics in high-Al-content AlGaN epilayers with different dislocation densities from 5 * 10(8) cm(-2) to 5 * 10(9) cm(-2) is studied by comparing the photoluminescence decay with the decay of carrier density. The carrier density decay was investigated using the light-induced transient grating technique. This comparison shows that the luminescence at the nonequilibrium carrier densities expected in operating light-emitting diodes depends on the recombination of free carriers and the localized exciton-like electron-hole pairs and localization delocalization processes. In addition, a fraction of the nonequilibrium carriers is captured by the deep capture centers with extremely long lifetimes. These carriers have an insignificant contribution to the band-to-band radiative recombination. This capture is an important factor in decreasing the emission efficiency. PMID- 26367623 TI - Origin of optical losses in gallium arsenide disk whispering gallery resonators. AB - Whispering gallery modes in GaAs disk resonators reach half a million of optical quality factor. These high Qs remain still well below the ultimate design limit set by bending losses. Here we investigate the origin of residual optical dissipation in these devices. A Transmission Electron Microscope analysis is combined with an improved Volume Current Method to precisely quantify optical scattering losses by roughness and waviness of the structures, and gauge their importance relative to intrinsic material and radiation losses. The analysis also provides a qualitative description of the surface reconstruction layer, whose optical absorption is then revealed by comparing spectroscopy experiments in air and in different liquids. Other linear and nonlinear optical loss channels in the disks are evaluated likewise. Routes are given to further improve the performances of these miniature GaAs cavities. PMID- 26367624 TI - Fast polarization-state tracking scheme based on radius-directed linear Kalman filter. AB - We propose and experimentally demonstrate a fast polarization tracking scheme based on radius-directed linear Kalman filter. It has the advantages of fast convergence and is inherently insensitive to phase noise and frequency offset effects. The scheme is experimentally compared to conventional polarization tracking methods on the polarization rotation angular frequency. The results show that better tracking capability with more than one order of magnitude improvement is obtained in the cases of polarization multiplexed QPSK and 16QAM signals. The influences of the filter tuning parameters on tracking performance are also investigated in detail. PMID- 26367625 TI - Thulium-doped fiber laser utilizing a photonic crystal fiber-based optical low pass filter with application in 1.7 MUm and 1.8 MUm band. AB - This paper describes a low pass filter based on photonics crystal fiber (PCF) partial ASE suppression, and its application within a 1.7 um to 1.8 um band thulium-doped fiber amplifier (TDFA) and a thulium-doped fiber laser (TDFL). The enlargement of air holes around the doped core region of the PCF resulted in a low-pass filter device that was able to attenuate wavelengths above the conventional long cut-off wavelength. These ensuing long cut-off wavelengths were 1.85 MUm and 1.75 MUm, and enabled a transmission mechanism that possessed a number of desirable characteristics. The proposed optical low-pass filter was applied within a TDFA and TDFL system. Peak spectrum was observed at around 1.9 MUm for conventional TDF lasers, while the proposed TDF laser with PCF setup had fiber laser peak wavelengths measured at downshifted values of 1.74 MUm and 1.81 MUm. PMID- 26367626 TI - 2.1 THz quantum-cascade laser operating up to 144 K based on a scattering assisted injection design. AB - A 2.1 THz quantum cascade laser (QCL) based on a scattering-assisted injection and resonant-phonon depopulation design scheme is demonstrated. The QCL is based on a four-well period implemented in the GaAs/Al0.15Ga0.85As material system. The QCL operates up to a heat-sink temperature of 144 K in pulsed-mode, which is considerably higher than that achieved for previously reported THz QCLs operating around the frequency of 2 THz. At 46 K, the threshold current-density was measured as ~ 745 A/cm2 with a peak-power output of ~10 mW. Electrically stable operation in a positive differential-resistance regime is achieved by a careful choice of design parameters. The results validate the robustness of scattering assisted injection schemes for development of low-frequency (nu < 2.5 THz) QCLs. PMID- 26367627 TI - Polarization rotation Bragg diffraction using Si wire waveguide grating and polarization rotator. AB - We report polarization independent Bragg grating wavelength filter with high diffraction efficiency. A rib waveguide polarization rotator and antisymmetric grating structure for fundamental to first order diffraction are used to generate the polarization rotation Bragg diffraction. The diffraction efficiencies and peak wavelengths become the same for two orthogonal input polarizations. Strong diffraction is attained easily. The concept was verified by simulation and experiment. Polarization independent band-pass filter consisting of polarization beam splitter and polarization rotation Bragg diffraction was experimentally demonstrated. PMID- 26367628 TI - Observation of coherent phonon-plasma coupled modes in wide gap semiconductors by transmission pump-probe measurements. AB - We have investigated coherent LO phonon properties in zinc-based II-VI widegap semiconductors, focusing on phonon-plasma coupled modes. By a careful treatment of the time evolution of the signals in ZnS, ZnSe, and ZnTe, we found a frequency upshift as the pump intensity increases. Using a classical coupled oscillator model, we have explained the pump intensity dependence of both the shift and the decay rates by a mixing of highly damped two-photon generated plasma. From the linear dependence between them we can estimate the photo-excited carrier mobilities, leading to a new powerful estimation method to measure the mobility. PMID- 26367629 TI - One- and two-photon photoluminescence excitation spectra of CdTe quantum dots in a cryogenic confocal microscopy platform. AB - In this work we describe a method to obtain photoluminescente excitation spectra, through one and two photon absorption, of CdTe quantum dots, based on a confocal microscope platform. This system becomes an analytical multipurpose characterization platform with spatial, and spectral resolution with temperature control. The capabilities of such platform were demonstrated by photoluminescence and second harmonic generation spectra acquisition as a function of temperature from 10 K to room temperature. The differences for one and two photons transition selection rules between the quantum dot confined levels provide access to intra and inter band, forbidden in one photon transitions, information that could be used to validate confinement models. The results agree well with the transition selection rules calculated with a parabolic model. PMID- 26367630 TI - Characterization of near-field ptychography. AB - Near-field X-ray ptychography has recently been proposed and shown to be able to retrieve a sample's complex-valued transmission function from multiple near-field diffraction images each with a lateral shift of the sample and with a structured (by a diffuser) illumination [Stockmar et al. Sci Rep. 3 (2013)]. In this paper, we undertake the first investigation - via numerical simulation - of the influence of the sampling and step size of the lateral shifts, the diffuser structure size, and the propagation distance on the reconstruction of the sample's transmission function. We find that for a gold Siemens star of thickness 750 nm with typical experimental parameters, for a successful reconstruction - given a theoretical minimum of four required measurements per imaged pixel - at least six diffraction images are required. PMID- 26367631 TI - Design methodology accounting for fabrication errors in manufactured modified Fresnel lenses for controlled LED illumination. AB - The increasing demand for lightweight, miniaturized electronic devices has prompted the development of small, high-performance optical components for light emitting diode (LED) illumination. As such, the Fresnel lens is widely used in applications due to its compact configuration. However, the vertical groove angle between the optical axis and the groove inner facets in a conventional Fresnel lens creates an inherent Fresnel loss, which degrades optical performance. Modified Fresnel lenses (MFLs) have been proposed in which the groove angles along the optical paths are carefully controlled; however, in practice, the optical performance of MFLs is inferior to the theoretical performance due to fabrication errors, as conventional design methods do not account for fabrication errors as part of the design process. In this study, the Fresnel loss and the loss area due to microscopic fabrication errors in the MFL were theoretically derived to determine optical performance. Based on this analysis, a design method for the MFL accounting for the fabrication errors was proposed. MFLs were fabricated using an ultraviolet imprinting process and an injection molding process, two representative processes with differing fabrication errors. The MFL fabrication error associated with each process was examined analytically and experimentally to investigate our methodology. PMID- 26367633 TI - Integrated electrically driven surface plasmon resonance device for biosensing applications. AB - Compact and portable surface plasmon resonance (SPR) biosensors of high sensitivities can be made through integration of discrete components in a single device. We report on a device comprising a vertical cavity light emitting diode (VLED) integrated with gold-based biosensing nanostructures fabricated atop its surface. Coupling of surface plasmon waves was achieved by the introduction of a spacer SiO2 layer located between the light source and the functionalized Au thin film. The SPR signal was extracted in far field with a Au-based nanograting and detected using a custom designed hyperspectral imager. We discuss the performance of a VLED-based SPR device employed for detection of different concentration saltwater solutions. PMID- 26367632 TI - Scanning color optical tomography (SCOT). AB - We have developed an interferometric optical microscope that provides three dimensional refractive index map of a specimen by scanning the color of three illumination beams. Our design of the interferometer allows for simultaneous measurement of the scattered fields (both amplitude and phase) of such a complex input beam. By obviating the need for mechanical scanning of the illumination beam or detection objective lens; the proposed method can increase the speed of the optical tomography by orders of magnitude. We demonstrate our method using polystyrene beads of known refractive index value and live cells. PMID- 26367634 TI - High-bandwidth transfer of phase stability through a fiber frequency comb. AB - We demonstrate phase locking of a 729 nm diode laser to a 1542 nm master laser via an erbium-doped-fiber frequency comb, using a transfer-oscillator feedforward scheme which suppresses the effect of comb noise in an unprecedented 1.8 MHz bandwidth. We illustrate its performance by carrying out coherent manipulations of a trapped calcium ion with 99 % fidelity even at few-MUs timescales. We thus demonstrate that transfer-oscillator locking can provide sufficient phase stability for high-fidelity quantum logic manipulation even without pre stabilization of the slave diode laser. PMID- 26367635 TI - Observation of discrete diffraction patterns in an optically induced lattice. AB - We have experimentally observed the discrete diffraction of light in a coherently prepared multi-level atomic medium. This is achieved by launching a probe beam into an optical lattice induced from the interference of two coupling beams. The diffraction pattern can be controlled through the atomic parameters such as two photon detuning and temperature, as well as orientations of the coupling and probe beams. Clear diffraction patterns occur only near the two-photon resonance. PMID- 26367636 TI - WDM-based radio frequency dissemination in a tree-topology fiber optic network. AB - In this paper, we propose and demonstrate a scheme to achieve point-to-multipoint dissemination of radio frequency (RF) signals in a local area fiber optic network with tree topology based on wavelength-division multiplexing (WDM) technique. The phase changes caused by the fluctuations of the transfer links are passively canceled at remote end instead of at local end, which makes it feasible to flexibly build a tree-topology local area dissemination network with great cost effectiveness. For the first time, we study the limit of long-term performance which is caused by temperature-induced variation of group velocity dispersion (TIVGVD) in dissemination networks using WDM techniques. In the proof-of-concept experiments, 38.5 km and 50 km fiber links are established to disseminate a 1 GHz frequency signal with fractional instability of 10(-17) order after 10(4) s averaging time. Then 17.4 nm wavelength spacing is introduced between local carrier and user carrier to verify the theoretical analysis. Under a controlled fiber temperature variation of about 21 degrees C, the obtained overlapping Allan deviation (ADEV) agrees well with the simulation results after 10(4) s time scales, which proves the validity of our theory. The theory has practical values in predicting and optimizing the capacity and performance of a WDM-based local area RF dissemination network. PMID- 26367637 TI - Realization of a flat-response photocathode for x-ray streak cameras. AB - We present a novel photocathode which can make x-ray streak cameras to be of a flat spectral response in the x-ray energy range of 0.1-5 keV. The photocathode consists of two layers of gold foils with optimized thickness ratio and structures. The photocathode was calibrated, and it is shown that a flat spectral response has been achieved. PMID- 26367638 TI - Cost-effective coherent PON using silicon Mach-Zehnder modulator and digital carrier regeneration. AB - We propose a cost-effective coherent passive optical network (PON) by employing the linear silicon Mach-Zehnder modulator (MZM) with computationally-efficient digital signal processing (DSP). The proposed PON adopts the intensity modulation and coherent detection scheme with discrete multi-tone (DMT) signal to achieve both high spectral efficiency (SE) and receiver sensitivity. Meanwhile, a digital carrier regeneration (DCR) method is proposed to further reduce the optical carrier-to-signal power ratio of intensity modulated DMT signal based on silicon MZM, which will significantly increase the achievable system power budget, especially when a high-order modulation format is adopted. No carrier frequency offset and phase estimations are needed in the receiver, which greatly reduces the complexity for both laser and DSP in coherent detection. Finally, a 10 Gb/s/ch uplink transmission is experimentally demonstrated using the proposed DCR method over 20-km standard single-mode fiber (SSMF), achieving about -44dBm sensitivity under the 7% forward-error-correction (FEC) limit of bit error ratio (BER) = 3.8x10(-3). PMID- 26367639 TI - Monolayer graphene saturable absorbers with strongly enhanced evanescent-field interaction for ultrafast fiber laser mode-locking. AB - We demonstrate an efficient all-fiber saturable absorber (SA) that evanescently interacts with a graphene monolayer. Strong nonlinear interaction between the graphene sheet and evanescent wave was realized in both experiments and numerical calculations by employing an over-cladding structure on high-quality monolayer graphene that uniformly covered the side-polished fiber. A passively mode-locked Er-doped fiber laser was built, including our in-line graphene SA, which stably generated ultrashort pulses with pulse duration of 377 fs at a repetition rate of 37.7 MHz. The corresponding 3-dB spectral bandwidth of the laser was measured to be 8.6 nm at the central wavelength of 1607.7 nm. We also experimentally observed that the spectral bandwidth and pulse duration of the laser output could be controlled by proper selection of the refractive index of the over-cladding material on the monolayer-graphene SA. PMID- 26367640 TI - Performance evaluation of peak-clipped optical BPSK-SSB modulated signal. AB - This study examines the performance of peak-clipped optical BPSK-SSB signal. The effectiveness of peak clipping for PAPR reduction and the degradation caused by peak clipping are numerically analyzed. PAPR of optical BPSK-SSB signal becomes high because of the peaky Hilbert-transformed signal component. PAPR improvement of 43.7% is attained by clipping the peaks of the Hilbert-transformed signal. Assessment of spectral degradation reveals that both waveform clipping and modulator nonlinearity contribute to sideband suppression degradation. Analyses of the 100-km transmitted signal results show that PAPR reduction by peak clipping alleviates the nonlinear phase shift caused by self-phase modulation (SPM), which produces a less degraded signal at the detector. Peak clipping can improve the SPM threshold of the studied system by 2.63 dB. PMID- 26367641 TI - Ppb-level formaldehyde detection using a CW room-temperature interband cascade laser and a miniature dense pattern multipass gas cell. AB - A ppb-level formaldehyde (H2CO) sensor was developed using a thermoelectrically cooled (TEC), continuous-wave (CW) room temperature interband cascade laser (ICL) emitting at 3.59 MUm and a miniature dense pattern multipass gas cell with >50 m optical path length. Performance of the sensor was investigated with two measurement schemes: direct absorption (DAS) and wavelength modulation spectroscopy (WMS). With an integration time of less than 1.5 second, a detection limit of ~3 ppbv for H2CO measurement with precision of 1.25 ppbv for DAS and 0.58 ppbv for WMS, respectively, was achieved without zero air based background subtraction. An Allan-Werle variance analysis indicated that the precisions can be further improved to 0.26 ppbv @ 300s for DAS and 69 pptv @ 90 s for WMS, respectively. A side-by-side comparison between two measurement schemes is also discussed in detail. PMID- 26367642 TI - Actively mode-locked Raman fiber laser. AB - Active mode-locking of Raman fiber laser is experimentally investigated for the first time. An all fiber connected and polarization maintaining loop cavity of ~500 m long is pumped by a linearly polarized 1120 nm Yb fiber laser and modulated by an acousto-optic modulator. Stable 2 ns width pulse train at 1178 nm is obtained with modulator opening time of > 50 ns. At higher power, pulses become longer, and second order Raman Stokes could take place, which however can be suppressed by adjusting the open time and modulation frequency. Transient pulse evolution measurement confirms the absence of relaxation oscillation in Raman fiber laser. Tuning of repetition rate from 392 kHz to 31.37 MHz is obtained with harmonic mode locking. PMID- 26367643 TI - Temperature and gain tuning of plasmonic coherent perfect absorbers. AB - We experimentally demonstrate temperature-tuned and gain-assisted surface plasmonic coherent perfect absorbers. In these devices, coherent perfect absorption (CPA) is supported by balancing the absorber's radiative and non radiative decay rates under thermal tuning of free-electron collision frequency in the Ag layer and optical tuning of the amplification rate in the adjacent dielectric film with optical gain, respectively. The results show that these methods are experimentally feasible and applicable to various CPA configurations. PMID- 26367644 TI - Bifractal focusing and imaging properties of Thue-Morse Zone Plates. AB - We present a new family of Zone Plates (ZPs) designed using the Thue-Morse sequence. The focusing and imaging properties of these aperiodic diffractive lenses coined Thue-Morse Zone Plates (TMZPs) are examined. It is demonstrated that TMZPs produce a pair of self-similar and equally intense foci along the optical axis. As a consequence of this property, under broadband illumination, a TMZP produces two foci with an extended depth of focus and a strong reduction of the chromatic aberration compared with conventional periodic ZPs. This distinctive optical characteristic is experimentally confirmed. PMID- 26367645 TI - Dynamic changes in PDMS surface morphology in femtosecond laser treatment. AB - We have investigated the effect of the dynamics of crater size on the poly(dimethylsiloxane) (PDMS) surface morphology in fs-laser micro-processing. PDMS surface was processed with varying both inter-pulse interval and inter-spot distance between successive laser pulses. With keeping the interval of 5 ms crater shape is round even if the spot is overlapped in space. But decreasing the interval to 0.02 ms the shape of the crater is no longer round. Decreasing the inter-distance between the craters results in roughened surface morphology even at time intervals of 5 ms. Temporal dependence of single-shot fs-laser induced crater size was measured as a function of time delay. Within 0.1 ms after pulse irradiation with a fluence of 4.8 J/cm2 on PDMS surface the crater size has reached to its maximum values and then decreased with a time constant of about 0.3 ms. The surface morphology after fs-laser pulse irradiation is strongly dependent on not only inter-spot distance between successive laser pulse but also their inter-pulse intervals. By proposing a theoretical model on their dynamic features, we will try to explain the current observation in quantitatively. PMID- 26367646 TI - Microcavity effect using nanoparticles to enhance the efficiency of organic light emitting diodes. AB - In this paper, in contrast with previously reported approaches, we suggest exploiting a microcavity effect using nanoparticles to improve the optical efficiency of organic light-emitting diodes (OLED). The method to input the nanoparticles inside the OLED device is simple and cost effective by virtue of employing a solution process using a spin coating fabrication method. Titanium dioxide (TiO2) nanoparticles were used to improve the reflection by its high refractive index. In tandem with optimized heights of the organic layers, the increased light reflectance at the anode side, which includes the TiO2 nanoparticle layer, improved the optical efficiency of the OLED device via the microcavity effect. In order to prove that the enhancement of the optical efficiency was due to an enhanced microcavity effect caused by TiO2 nanoparticles, a microcavity simulation was conducted. The electrical characteristics were not affected by the nanoparticles and a clear pixel image was maintained. The results in this paper show that a nanoparticle based microcavity effect can be exploited to enhance the optical efficiency of OLEDs. PMID- 26367647 TI - Hybrid wireless-over-fiber transmission system based on multiple injection-locked FP LDs. AB - A hybrid wireless-over-fiber (WoF) transmission system based on multiple injection-locked Fabry-Perot laser diodes (FP LDs) is proposed and experimentally demonstrated. Unlike the traditional hybrid WoF transmission systems that require multiple distributed feedback (DFB) LDs to support different kinds of services, the proposed system employs multiple injection-locked FP LDs to provide different kinds of applications. Such a hybrid WoF transmission system delivers downstream intensity-modulated 20-GHz microwave (MW)/60-GHz millimeter-wave (MMW)/550-MHz cable television (CATV) signals and upstream phase-remodulated 20-GHz MW signal. Excellent bit error rate (BER), carrier-to-noise ratio (CNR), composite second order (CSO), and composite triple-beat (CTB) are observed over a 40-km single mode fiber (SMF) and a 4-m radio frequency (RF) wireless transport. Such a hybrid WoF transmission system has practical applications for fiber-wireless convergence to provide broadband integrated services, including telecommunication, data communication, and CATV services. PMID- 26367648 TI - Physical mechanisms for tuning the nonlinear effects in photonic crystals. AB - By simultaneously taking field localization and slow light effects into account, in this paper we make use of a field averaging method to calculate the effective nonlinear refractive index coefficient (n2) of Kerr photonic crystals (PhCs) in the first band. Although the nonlinear PhC is beyond the traditional long wavelength limit, interestingly, the theoretically calculated effective n2 agrees well with one numerically measured via the self-phase-modulation induced spectral broadening. Moreover, due to the cooperative influence of field localization and slow light effects, the effective n2 of the PhC decreases slowly at first and then goes up quickly with increasing frequency. This kind of dispersive nonlinearity is purely induced by the periodic nanostructures because the optical parameters of both components of the PhC we took are frequency-independent. Our results may pave the way for enhancing or limiting nonlinear effects and provide a method for producing the dispersive nonlinearity. PMID- 26367649 TI - Widely-tunable low-phase-noise coherent receiver using an optical Wadley loop. AB - The Wadley Loop is a method of down-converting RF signals over a wide frequency range using a low-quality widely-tunable oscillator and a high-stability frequency comb reference. Together the widely tunable oscillator and high stability comb source provide a widely-tunable high-stability receiver. In this paper, we demonstrate an electro-optic version of the Wadley Loop that is able to provide a widely-tunable, high phase stability coherent receiver. This could have applications in Quadrature Amplitude Modulation (QAM) receivers with high constellation sizes, optical OFDM receivers with long symbol durations, and wide range high spectral resolution optical spectrum analysers. PMID- 26367650 TI - Multi-functional lens based on conformal mapping. AB - Based on conformal mapping method, a two dimensional, multi-functional lens structure is proposed and designed in this work. The lens is an infinitely-long, gradient-index dielectric cylinder with a semi-elliptic cross-section. The lens can first be considered like a flattened Luneburg lens, which produces highly directive electromagnetic waves by adjusting the feed position along the line connecting the two foci. It also functions like an Eaton lens. When an incoming beam impinges on the same line but outside the two foci, it will be guided through the lens structure and take a U-turn. Besides, if properly shaped, the structure can also be used as a waveguide bend. The lens can be realized using non-resonant metamaterials with inhomogeneous hole arrays. Simulation results demonstrate excellent performance of the lens and agree well with theoretical prediction. The designed lens can be used in the electromagnetic control. And it is especially useful in the real optical lens system. PMID- 26367651 TI - Coherent diffractive imaging beyond the projection approximation: waveguiding at extreme ultraviolet wavelengths. AB - We study extreme-ultraviolet wave propagation within optically thick nanostructures by means of high-resolution coherent diffractive imaging using high-harmonic radiation. Exit waves from different objects are reconstructed by phase retrieval algorithms, and are shown to be dominated by waveguiding within the sample. The experiments provide a direct visualization of extreme-ultraviolet guided modes, and demonstrate that multiple scattering is a generic feature in extruded nanoscale geometries. The observations are successfully reproduced in numerical and semi-analytical simulations. PMID- 26367652 TI - Single-mode lasers and parity-time symmetry broken gratings based on active dielectric-loaded long-range surface plasmon polariton waveguides. AB - Single-mode distributed feedback laser structures and parity-time symmetry broken grating structures based on dielectric-loaded long-range surface plasmon polariton waveguides are proposed. The structures comprise a thin Ag stripe on an active polymer bottom cladding with an active polymer ridge. The active polymer assumed is PMMA doped with IR140 dye providing optical gain at near infrared wavelengths. Cutoff top ridge dimensions (thickness and width) are calculated using a finite element method and selected to guarantee single-mode operation of the laser. Several parameters such as the threshold number of periods and the lasing wavelength are determined using the transfer matrix method. A related structure based on two pairs of waveguides of two widths, which have the same imaginary part but different real part of effective index, arranged within one grating period, is proposed as an active grating operating at the threshold for parity-time symmetry breaking (i.e., operating at an exceptional point). Such "exceptional point" gratings produce ideal reflectance asymmetry as demonstrated via transfer matrix computations. PMID- 26367653 TI - Phase shifting interferometry from two normalized interferograms with random tilt phase-shift. AB - We propose a novel phase shifting interferometry from two normalized interferograms with random tilt phase-shift. The determination of tilt phase shift is performed by extracting the tilted phase-shift plane from the phase difference of two normalized interferograms, and with the calculated tilt phase shift value the phase distribution can be retrieved from the two normalized frames. By analyzing the distribution of phase difference and utilizing special points fitting method, the tilted phase-shift plane is extracted in three different cases, which relate to different magnitudes of tilts. Proposed method has been applied to simulations and experiments successfully and the satisfactory results manifest that proposed method is of high accuracy and high speed compared with the three step iterative method. Additionally, both open and closed fringe can be analyzed with proposed method. What's more, it cannot only eliminate the small tilt-shift error caused by slight vibration in phase-shifting interferometry, but also detect the large tilt phase-shift in phase-tilting interferometry. Thus, it will relaxes the requirements on the accuracy of phase shifter, and the costly phase shifter may even be useless by applying proposed method in high amplitude vibrated circumstance to achieve high-precision analysis. PMID- 26367654 TI - Intra-cavity frequency-doubled mode-locked semiconductor disk laser at 325 nm. AB - We present a passively mode-locked semiconductor disk laser (SDL) emitting at 650nm with intra-cavity second harmonic generation to the ultraviolet (UV) spectral range. Both the gain and the absorber structure contain InP quantum dots (QDs) as active material. In a v-shaped cavity using the semiconductor samples as end mirrors, a beta barium borate (BBO) crystal is placed in front of the semiconductor saturable absorber mirror (SESAM) for pulsed UV laser emission in one of the two outcoupled beams. Autocorrelation (AC) measurements at the fundamental wavelength reveal a FWHM pulse duration of 1.22ps. With a repetition frequency of 836MHz, the average output power is 10mW per beam for the red emission and 0.5mW at 325nm. PMID- 26367655 TI - 100 Gbps IM/DD links using quad-polarization: Performance, complexity, and power dissipation. AB - A computational complexity, power consumption, and receiver sensitivity analysis for three different scenarios for short-range direct detection links is presented: 1) quad-polarization, 2) wavelength division multiplexing (WDM), and 3) parallel optics. Results show that the power consumption penalty associated to the quad-polarization digital signal processing (DSP) is negligibly small. However, the required analog to digital converters account for 47.6% of the total system power consumption. Transmission of 4*32 Gbps over 2 km standard single mode fiber is achieved with a receiver sensitivity of 4.4 dBm. PMID- 26367656 TI - High Q factor chalcogenide ring resonators for cavity-enhanced MIR spectroscopic sensing. AB - We report the characteristics of high Q factor chalcogenide ring resonators designed for sensing in the mid-infrared (MIR). The resonators consisted of an exposed Ge11.5As24Se64.5 core on a Ge11.5As24S64.5 bottom cladding and were fabricated in the racetrack coupled ring structure. Loaded Q factors at 5.2MUm up to 58,000were obtained, corresponding to an intrinsic Q of 145,000 and a waveguide propagation loss of 0.84dB/cm. PMID- 26367657 TI - Quantitative evaluation on internal seeing induced by heat-stop of solar telescope. AB - heat-stop is one of the essential thermal control devices of solar telescope. The internal seeing induced by its temperature rise will degrade the imaging quality significantly. For quantitative evaluation on internal seeing, an integrated analysis method based on computational fluid dynamics and geometric optics is proposed in this paper. Firstly, the temperature field of the heat-affected zone induced by heat-stop temperature rise is obtained by the method of computational fluid dynamics calculation. Secondly, the temperature field is transformed to refractive index field by corresponding equations. Thirdly, the wavefront aberration induced by internal seeing is calculated by geometric optics based on optical integration in the refractive index field. This integrated method is applied in the heat-stop of the Chinese Large Solar Telescope to quantitatively evaluate its internal seeing. The analytical results show that the maximum acceptable temperature rise of heat-stop is up to 5 Kelvins above the ambient air at any telescope pointing directions under the condition that the root-mean square of wavefront aberration induced by internal seeing is less than 25nm. Furthermore, it is found that the magnitude of wavefront aberration gradually increases with the increase of heat-stop temperature rise for a certain telescope pointing direction. Meanwhile, with the variation of telescope pointing varying from the horizontal to the vertical direction, the magnitude of wavefront aberration decreases at first and then increases for the same heat-stop temperature rise. PMID- 26367658 TI - Mode-locked, 1.94-MUm, all-fiberized laser using WS2 based evanescent field interaction. AB - We demonstrate the use of an all-fiberized, mode-locked 1.94 MUm laser with a saturable absorption device based on a tungsten disulfide (WS2)-deposited side polished fiber. The WS2 particles were prepared via liquid phase exfoliation (LPE) without centrifugation. A series of measurements including Raman spectroscopy, scanning electron microscopy (SEM), and atomic force microscopy (AFM) revealed that the prepared particles had thick nanostructures of more than 5 layers. The prepared saturable absorption device used the evanescent field interaction mechanism between the oscillating beam and WS2 particles and its modulation depth was measured to be ~10.9% at a wavelength of 1925 nm. Incorporating the WS2-based saturable absorption device into a thulium-holmium co doped fiber ring cavity, stable mode-locked pulses with a temporal width of ~1.3 ps at a repetition rate of 34.8 MHz were readily obtained at a wavelength of 1941 nm. The results of this experiment confirm that WS2 can be used as an effective broadband saturable absorption material that is suitable to passively generate pulses at 2 MUm wavelengths. PMID- 26367659 TI - Polymer-stabilized blue-phase liquid crystal grating cured with interfered visible light. AB - In this paper, we demonstrate a holographic polymer-stabilized blue-phase liquid crystal grating fabricated using a visible laser. As blue phase is stabilized by the interfered light, polymer-concentration gradient is achieved simultaneously. With the application of a uniform vertical electric field, periodic index distribution is obtained due to polymer-concentration gradient. The grating exhibits several attractive features such as polarization-independency, a broad temperature range, sub-millisecond response, simple fabrication, and low cost, thus holding great potential for photonics applications. PMID- 26367660 TI - Concentric circle scanning system for large-area and high-precision imaging. AB - Large-area manufacturing surfaces containing micro- and nano-scale features and large-view biomedical targets motivate the development of large-area, high resolution and high-speed imaging systems. Compared to constant linear velocity scans and raster scans, constant angular velocity scans can significantly attenuate transient behavior while increasing the speed of imaging. In this paper, we theoretically analyze and evaluate the speed, acceleration and jerks of concentric circular trajectory sampling (CCTS). We then present a CCTS imaging system that demonstrates less vibration and lower mapping errors than raster scanning for creating a Cartesian composite image, while maintaining comparably fast scanning speed for large scanning area. PMID- 26367661 TI - Microfiber-based few-layer black phosphorus saturable absorber for ultra-fast fiber laser. AB - Few-layer black phosphorus (BP), as the most alluring graphene analogue owing to its similar structure as graphene and thickness dependent direct band-gap, has now triggered a new wave of research on two-dimensional (2D) materials based photonics and optoelectronics. However, a major obstacle of practical applications for few-layer BPs comes from their instabilities of laser-induced optical damage. Herein, we demonstrate that, few-layer BPs, which was fabricated through the liquid exfoliation approach, can be developed as a new and practical saturable absorber (SA) by depositing few-layer BPs with microfiber. The saturable absorption property of few-layer BPs had been verified through an open aperture z-scan measurement at the telecommunication band. The microfiber-based BP device had been found to show a saturable average power of ~4.5 mW and a modulation depth of 10.9%, which is further confirmed through a balanced twin detection measurement. By integrating this optical SA device into an erbium-doped fiber laser, it was found that it can deliver the mode-locked pulse with duration down to 940 fs with central wavelength tunable from 1532 nm to 1570 nm. The prevention of BP from oxidation through the "lateral interaction scheme" owing to this microfiber-based few-layer BP SA device might partially mitigate the optical damage problem of BP. Our results not only demonstrate that black phosphorus might be another promising SA material for ultrafast photonics, but also provide a practical solution to solve the optical damage problem of black phosphorus by assembling with waveguide structures such as microfiber. PMID- 26367662 TI - Time-frequency methods for coherent spectroscopy. AB - Time-frequency decomposition techniques, borrowed from the signal-processing field, have been adapted and applied to the analysis of 2D oscillating signals. While the Fourier-analysis techniques available so far are able to interpret the information content of the oscillating signal only in terms of its frequency components, the time-frequency transforms (TFT) proposed in this work can instead provide simultaneously frequency and time resolution, unveiling the dynamics of the relevant beating components, and supplying a valuable help in their interpretation. In order to fully exploit the potentiality of this method, several TFTs have been tested in the analysis of sample 2D data. Possible artifacts and sources of misinterpretation have been identified and discussed. PMID- 26367663 TI - Wideband saturable absorption in few-layer molybdenum diselenide (MoSe2) for Q switching Yb-, Er- and Tm-doped fiber lasers. AB - We fabricate a free-standing molybdenum diselenide (MoSe2) saturable absorber by embedding liquid-phase exfoliated few-layer MoSe2 flakes into a polymer film. The MoSe2-polymer composite is used to Q-switch fiber lasers based on ytterbium (Yb), erbium (Er) and thulium (Tm) gain fiber, producing trains of microsecond-duration pulses with kilohertz repetition rates at 1060 nm, 1566 nm and 1924 nm, respectively. Such operating wavelengths correspond to sub-bandgap saturable absorption in MoSe2, which is explained in the context of edge-states, building upon studies of other semiconducting transition metal dichalcogenide (TMD)-based saturable absorbers. Our work adds few-layer MoSe2 to the growing catalog of TMDs with remarkable optical properties, which offer new opportunities for photonic devices. PMID- 26367664 TI - Bayesian approach to time-resolved tomography. AB - Conventional X-ray micro-computed tomography (MUCT) is unable to meet the need for real-time, high-resolution, time-resolved imaging of multi-phase fluid flow. High signal-to-noise-ratio (SNR) data acquisition is too slow and results in motion artefacts in the images, while fast acquisition is too noisy and results in poor image contrast. We present a Bayesian framework for time-resolved tomography that uses priors to drastically reduce the required amount of experiment data. This enables high-quality time-resolved imaging through a data acquisition protocol that is both rapid and high SNR. Here we show that the framework: (i) encompasses our previous, algorithms for imaging two-phase flow as limiting cases; (ii) produces more accurate results from imperfect (i.e. real) data, where it can be compared to our previous work; and (iii) is generalisable to previously intractable systems, such as three-phase flow. PMID- 26367665 TI - Athermal and wavelength-trimmable photonic filters based on TiO2-cladded amorphous-SOI. AB - Large-scale integrated silicon photonic circuits suffer from two inevitable issues that boost the overall power consumption. First, fabrication imperfections even on sub-nm scale result in spectral device non-uniformity that require fine tuning during device operation. Second, the photonic devices need to be actively corrected to compensate thermal drifts. As a result significant amount of power is wasted if no athermal and wavelength-trimmable solutions are utilized. Consequently, in order to minimize the total power requirement of photonic circuits in a passive way, trimming methods are required to correct the device inhomogeneities from manufacturing and athermal solutions are essential to oppose temperature fluctuations of the passive/active components during run-time. We present an approach to fabricate CMOS backend-compatible and athermal passive photonic filters that can be corrected for fabrication inhomogeneities by UV trimming based on low-loss amorphous-SOI waveguides with TiO2 cladding. The trimming of highly confined 10 MUm ring resonators is proven over a free spectral range retaining athermal operation. The athermal functionality of 2nd-order 5 MUm add/drop microrings is demonstrated over 40 degrees C covering a broad wavelength interval of 60 nm. PMID- 26367666 TI - Negative coupling and coupling phase dispersion in a silicon quadrupole micro racetrack resonator. AB - We report the first experimental study of the effects of coupling phase dispersion on the spectral response of a two-dimensionally coupled quadrupole micro-racetrack resonator. Negative coupling in the system is observed to manifest itself in the sharp stop band transition and deep extinction in the pseudo-elliptic filter response of the quadrupole. The results demonstrate the feasibility of realizing advanced silicon microring devices based on the 2D coupling topology with general complex coupling coefficients. PMID- 26367667 TI - Modulation of photonic nanojets generated by microspheres decorated with concentric rings. AB - A novel design of decorating microsphere surface with concentric rings to modulate the photonic nanojet (PNJ) is investigated. By introducing the concentric ring structures into the illumination side of the microspheres, a reduction of the full width at half maximum (FWHM) intensity of the PNJ by 29.1%, compared to that without the decoration, can be achieved numerically. Key design parameters, such as ring number and depth, are analyzed. Engineered microsphere with four uniformly distributed rings etched at a depth of 1.2 MUm and width of 0.25 MUm can generate PNJ at a FWHM of 0.485 lambda (lambda = 400nm). Experiments were carried out by direct observation of the PNJ with an optical microscope under 405 nm laser illumination. As a result, shrinking of PNJ beam size of 28.0% compared to the case without the rings has been achieved experimentally. Sharp FWHM of this design can be beneficial to micro/nanoscale fabrication, optical super-resolution imaging, and sensing. PMID- 26367668 TI - Characteristic investigation of scanning surface plasmon microscopy for nucleotide functionalized nanoarray. AB - A calculation based on surface plasmon coupling condition and Maxwell-Garnett equation was performed for predicting the coupling angle shift and thin film thickness in scanning surface plasmon microscopy (SSPM). The refractive index sensitivity and lateral resolution of an SSPM system was also investigated. The limit of detection of angle shift was 0.01 degrees , the limit of quantification of angle shift was 0.03 degrees , and the sensitivity was around 0.12 degrees shift per nm ZnO film when the film thickness was less than 22.6 nm. Two partially connected Au nano-discs with a center-to-center distance of 1.1 MUm could be identified as two peaks. The system was applied to image nanostructure defects and a virus-probe functionalized nanoarray. We expect the potential application in nanobiosensors with further optimization in the future. PMID- 26367669 TI - Bendable, ultra-black absorber based on a graphite nanocone nanowire composite structure. AB - A bendable ultra-black material consisting of graphite nanocones and nanowires is fabricated through a simple plasma etching process. The optical properties of the absorber are characterized in the wavelength range of 400-2000 nm with average specular reflectance 0.05 +/- 0.03% at normal incidence and the material thickness is only around 5 MUm. The reflectance of the absorber remains low at large incident angles and is relatively independent of polarization. Simulations confirm the cooperative effect of the nanowires and nanocones leading to an ultra black thin carbon material. PMID- 26367670 TI - Metallic planar lens formed by coupled width-variable nanoslits for superfocusing. AB - We report a metallic planar lens based on the coupled nanoslits with variable widths for superfocusing. The influence of the interaction between two adjacent nanoslits on the phase delay is systematically investigated using the finite difference time-domain (FDTD) method. Based on the geometrical optics and the wavefront reconstruction theory, an array of nanoslits perforated in a gold film is optimally designed to achieve the desired phase modulation for light beaming. The simulation result verifies our design in excellent agreement and the realized metallic lens reveals the superfocusing capability of 0.38lambda in resolution, well beyond the diffraction limit. PMID- 26367671 TI - Lab-on-fiber optofluidic platform for in situ monitoring of drug release from therapeutic eluting polyelectrolyte multilayers. AB - A lab-on-fiber (LOF) optofluidic platform that provides physiologically relevant microenvironment was developed by integrating a long period grating (LPG) coupled with high order cladding mode to achieve high index sensitivity and a liquid tight capillary tube assembly as a microfluidic chamber for LPG to mimic physiologically relevant microenvironment. We demonstrate the utility of LOF for in situ monitoring the construction of the [chitosan (CHI)/poly (acrylic acid) (PAA)/gentamicin sulfate (GS)/PAA]n multilayers at monolayer resolution as well as evaluating the rate of GS release at a flow rate of 0.127 mL/min at 37 degrees C in real time. We reveal that GS is released at a faster rate under the dynamic flow condition than in a static medium. Our findings underscore the importance of conducting drug release studies in physiologically relevant conditions. PMID- 26367672 TI - Internal optical forces in plasmonic nanostructures. AB - We present a computational study of the internal optical forces arising in plasmonic gap antennas, dolmen structures and split rings. We find that very strong internal forces perpendicular to the propagation direction appear in these systems. These internal forces show a rich behaviour with varying wavelength, incident polarisation and geometrical parameters, which we explain in terms of the polarisation charges induced on the structures. Various interesting and anomalous features arise such as lateral force reversal, optical pulling force, and circular polarisation-induced forces and torques along directions symmetry forbidden for orthogonal linear polarisations. Understanding these effects and mastering internal forces in plasmonic nanostructures will be instrumental in implementing new functionalities in these nanophotonic systems. PMID- 26367673 TI - Benefit of adaptive FEC in shared backup path protected elastic optical network. AB - We apply an adaptive forward error correction (FEC) allocation strategy to an Elastic Optical Network (EON) operated with shared backup path protection (SBPP). To maximize the protected network capacity that can be carried, an Integer Linear Programing (ILP) model and a spectrum window plane (SWP)-based heuristic algorithm are developed. Simulation results show that the FEC coding overhead required by the adaptive FEC scheme is significantly lower than that needed by a fixed FEC allocation strategy resulting in higher network capacity for the adaptive strategy. The adaptive FEC allocation strategy can also significantly outperform the fixed FEC allocation strategy both in terms of the spare capacity redundancy and the average FEC coding overhead needed per optical channel. The proposed heuristic algorithm is efficient and not only performs closer to the ILP model but also does much better than the shortest-path algorithm. PMID- 26367674 TI - Generation of low repetition rate subnanosecond pulse in an optimal doubly QML Nd:Lu0.15Y0.85VO4 laser with EO and Cr4+:YAG. AB - Employing different output couplers and Cr4+:YAG saturable absorbers with different initial transmittances in a Q-switched mode-locked (QML) Nd:Lu0.15Y0.85VO4 laser, the symmetry of the Q-switched envelope was optimized and the envelope duration was shortened. By applying the above mentioned optimization into an EO/Cr4+:YAG dual-loss-modulated QML Nd:Lu0.15Y0.85VO4 laser, the Q-switched envelope can be further compressed until only containing one mode locking pulse. Mode-locking pulse energy and peak power up to 1.15 mJ and 3.15 MW, respectively, were achieved. The rate equation theory was utilized to analyze the experimental results, and the theoretical simulation was basically in accordance with the experimental data. PMID- 26367675 TI - Tunable Stokes laser generation based on the stimulated polariton scattering in KTiOPO4 crystal. AB - The tunable Stokes laser characteristics based on the stimulated polariton scattering in KTiOPO4 (KTP) crystal and the intracavity frequency doubling properties for the Stokes laser are investigated for the first time. When the pumping laser wavelength is 1064.2 nm, and the angle between the pumping and Stokes beams outside the KTP crystal changes from 1.875 degrees to 6.750 degrees , the obtained tunable Stokes laser wavelength varies discontinuously from 1076.5 nm to 1091.4 nm with four gaps. When the pumping pulse energy is 120.0 mJ, the maximum Stokes pulse energy is 46.5 mJ obtained at the wavelength of 1086.6 nm. By inserting a LiB3O5 (LBO) crystal into the cavity, the obtained frequency doubled laser wavelength is inconsecutive tunable from 538.5 nm to 543.8 nm. The maximum frequency-doubled laser pulse energy is 15.9 mJ at the wavelength of 543.5 nm. PMID- 26367676 TI - Spectral narrowing of Yb:YAG waveguide lasers through hybrid integration with ultrafast laser written Bragg gratings. AB - Laser written waveguides in crystalline materials can be used to make highly efficient, high gain lasers. The bi-directional emission from such lasers however is typically broadband with poor spectral control. Hybridizing a tapered, mode matched laser written Bragg grating with a broadband Yb:YAG crystalline waveguide laser, we demonstrate single longitudinal mode output from one end of the device. Careful control of the grating characteristics led to laser thresholds below 90 mW, slope efficiencies greater than 42% and output powers greater than 20 mW. PMID- 26367677 TI - Forward research on transmission characteristics of near-surface particulate matter-polluted atmosphere in mining area combined with CFD method. AB - The optical radiation and radiation transfer characteristics of atmospheric particulate matter (PM) in mining area of northwest China were simulated and analyzed in this paper. Computational fluid dynamics (CFD) method was adopted to simulate the distribution of PM considering the local desertification and mining activities. The 1-D radiative transfer equation was solved using discrete ordinates method combined with Mie scattering model based on the CFD simulation results. The spectral aerosol optical depth and transmission characteristics of PM polluted atmosphere in the wavelength of 1-25MUm under different intensity of dust releases, wind speeds and dust compositions were obtained and analyzed. The simulation results show that: the transmission characteristics are obviously enhanced with the increase of wind speed and sand particles' proportion but greatly decreased with the increase of the intensity of dust release. PMID- 26367678 TI - Chromaticity tailorable glass-based phosphor-converted white light-emitting diodes with high color rendering index. AB - In this paper, Lu3Al5O12:Ce3+ and CaAlSiN3: Eu2+ co-doped glass are presented as color conversion materials for white light-emitting diodes (WLEDs). Through adjusting the thickness of the glass phosphors, the chromaticity and CCT of the WLEDs follows the Planckian locus well. The WLEDs show CCT ranging from ~4000K to ~7000K with high CRI ranging from 83 to 90 due to the wide emission spectrum from the proposed glass phosphors. The glass phosphors provide an effective way to achieve chromaticity-tailorable WLEDs with high color quality for indoor lighting applications. PMID- 26367679 TI - Broadband high efficiency silicon nanowire arrays with radial diversity within diamond-like geometrical distribution for photovoltaic applications. AB - In this study we report novel silicon nanowire (SiNW) array structures that have near-unity absorption spectrum. The design of the new SiNW arrays is based on radial diversity of nanowires with periodic diamond-like array (DLA) structures. Different array structures are studied with a focus on two array structures: limited and broad diversity DLA structures. Numerical electromagnetic modeling is used to study the light-array interaction and to compute the optical properties of SiNW arrays. The proposed arrays show superior performance over other types of SiNW arrays. Significant enhancement of the array absorption is achieved over the entire solar spectrum of interest with significant reduction of the amount of material. The arrays show performance independent of angle of incidence up to 70 degrees, and polarization. The proposed arrays achieved ultimate efficiency as high as 39% with filling fraction as low as 19%. PMID- 26367680 TI - Modeling photovoltaic performance in periodic patterned colloidal quantum dot solar cells. AB - Colloidal quantum dot (CQD) solar cells have attracted tremendous attention mostly due to their wide absorption spectrum window and potentially low processability cost. The ultimate efficiency of CQD solar cells is highly limited by their high trap state density. Here we show that the overall device power conversion efficiency could be improved by employing photonic structures that enhance both charge generation and collection efficiencies. By employing a two dimensional numerical model, we have calculated the characteristics of patterned CQD solar cells based of a simple grating structure. Our calculation predicts a power conversion efficiency as high as 11.2%, with a short circuit current density of 35.2 mA/cm2, a value nearly 1.5 times larger than the conventional flat design, showing the great potential value of patterned quantum dot solar cells. PMID- 26367681 TI - Analysis of wide color gamut of green/red bilayered freestanding phosphor film capped white LEDs for LCD backlight. AB - In this study, we propose green/red bilayered freestanding phosphor film-capped white light-emitting diodes (W-LEDs) using InGaN blue LEDs and narrowband red and green phosphors to realize a wide color gamut in a liquid crystal display (LCD) backlight system. The narrowband K2SiF6:Mn4+ (KSF) red and SrGa2S4:Eu2+ (SGS) green phosphors are synthesized using a facile etching synthetic process and flux aided solid state reaction under a H2S atmosphere, respectively, and the freestanding phosphor films are fabricated using a delamination method with water soluble polymer, polystyrene sulfonic acid, PEDOT/PSS, and interlayered phosphor film. Various phosphor concentrations of green/red bilayered freestanding phosphor film-capped W-LEDs exhibit a correlated color temperature (CCT) and luminous efficacy range of 11,390 K ~6,540 K and 99 lm/W ~124 lm/W, respectively, with an applied current of 60 mA. The W-LED with green (12.5 wt%)/red (40 wt%) bilayered phosphor film, which exhibited luminous efficacy of 105 lm/W at the CCT of 8,330 K, is selected and the color gamut of the bare LED and phosphor RG and the filtered RGB triangle is calculated to be more than ~95% and ~86.4%, respectively, relative to the NTSC in the 1931 CIE color coordinates space. PMID- 26367682 TI - Liquid filled prismatic louver facade for enhanced daylighting in high-rise commercial buildings. AB - A liquid filled prismatic louver (LFPL) facade that can perform daylight and thermal energy harvesting with the potential to offer enhanced natural illumination levels to office spaces and thermally assist secondary thermal driven applications is proposed and analyzed. We focus the present simulation study on the evaluation of daylight enhancement in indoor space by redirecting light from a window opening to the ceiling of the room, and then-after a diffusive reflection from the ceiling-onward to the work plane of the room. Illumination simulations using LightTools, a forward ray tracing illumination simulation software, are performed for an office building space located in New York City. We show that the LFPL system achieves deeper natural light penetration, better uniformity and higher illuminance levels compared to an office space without the LFPL system. We further extend our study to a number of other representative cities in the continental US, covering different climatic zones. The LFPL system achieves good daylight harvesting performance. Finally, we discuss the potential of the LFPL system to capture solar infrared radiation heat within the liquid (e.g., water) volume and use it to assist in secondary thermal energy applications. PMID- 26367683 TI - Light extraction from electroluminescent devices using micro-rod array embedded within glass substrate. AB - The total internal reflection (TIR) effect in conventional electroluminescent devices causes a large amount of light energy trapped in the devices and result in heat energy that adversely affects the performance of the device. In order to enhance the light out-coupling efficiency without sacrificing the electrical properties, a micro-rod array (MRA) structure fabricated by a femtosecond laser was demonstrated. Green, blue, and red organic light-emitting diodes were employed to verify the effect of the proposed method, which increases out coupling efficiencies by a factor of 1.9, 1.7, and 1.82, respectively, compared with conventional devices. This highly effective method is compatible with current device fabrication processes and is applicable to full-color electroluminescent devices. PMID- 26367684 TI - Numerical modeling of the radiative transfer in a turbid medium using the synthetic iteration. AB - In this paper we propose the fast, but the accurate algorithm for numerical modeling of light fields in the turbid media slab. For the numerical solution of the radiative transfer equation (RTE) it is required its discretization based on the elimination of the solution anisotropic part and the replacement of the scattering integral by a finite sum. The solution regular part is determined numerically. A good choice of the method of the solution anisotropic part elimination determines the high convergence of the algorithm in the mean square metric. The method of synthetic iterations can be used to improve the convergence in the uniform metric. A significant increase in the solution accuracy with the use of synthetic iterations allows applying the two-stream approximation for the regular part determination. This approach permits to generalize the proposed method in the case of an arbitrary 3D geometry of the medium. PMID- 26367685 TI - Performance optimization of dense-array concentrator photovoltaic system considering effects of circumsolar radiation and slope error. AB - This paper presents an approach to optimize the electrical performance of dense array concentrator photovoltaic system comprised of non-imaging dish concentrator by considering the circumsolar radiation and slope error effects. Based on the simulated flux distribution, a systematic methodology to optimize the layout configuration of solar cells interconnection circuit in dense array concentrator photovoltaic module has been proposed by minimizing the current mismatch caused by non-uniformity of concentrated sunlight. An optimized layout of interconnection solar cells circuit with minimum electrical power loss of 6.5% can be achieved by minimizing the effects of both circumsolar radiation and slope error. PMID- 26367686 TI - Ray-trace simulation of CuInS(Se)2 quantum dot based luminescent solar concentrators. AB - To enhance the performance of luminescent solar concentrator (LSC), there is an increased need to search novel emissive materials with broad absorption and large Stokes shifts. I-III-VI colloidal CuInS2 and CuInSe2 based nanocrystals, which exhibit strong photoluminescence emissions in the visible to near infrared region with large Stokes shifts, are expected to improve performance in luminescent solar concentrator applications. In this work, the performance of CuInS(Se)2 quantum dots in simple planar LSC is evaluated by applying Monte-Carlo ray-trace simulation. A systematic parameters study was conducted to optimize the performance. An optimized photon concentration ratio of 0.34 for CuInS2 nanocrystals and 1.25 for CuInSe2 nanocrystals doping LSC are obtained from the simulation. The results demonstrated that CuInSe2 based nanocrystals are particularly interesting for luminescent solar concentrator applications, especially to combine with low price Si solar cells. PMID- 26367687 TI - Persistent phosphor SrAl2O4:Eu,Dy in outdoor conditions: saved by the trap distribution. AB - Persistent phosphors are a specific type of luminescent materials having the unique ability to emit light long after the excitation has ended. They are commonly used as emergency signage in near ideal, isothermal indoor situations. Recently, their energy storage capacity was relied on for outdoor situations, e.g. for glow-in-the-dark road marks and in combination with solar cells and photo catalytic processes. In this work the influence of temperature, illumination intensity and the duration of the night is critically evaluated on the performance of afterglow phosphors. The persistent luminescence of SrAl2O4:Eu,Dy green emitting phosphors is studied under realistic and idealized conditions. It is found that the light output profile is hardly influenced by the ambient temperature in a wide range. This is due to the presence of a broad trap depth distribution, which is beneficial to cover the longer and colder winter nights. Temperature drops during the night are however detrimental. For traffic applications, the total light output of glow-in-the-dark road marks at the end of the night is not sufficient for the studied compound, although re-charging by the car's headlamps partially alleviates this. For energy storage applications, the trap density should be improved and tunneling recombination processes might be needed to overcome overnight temperature drops. PMID- 26367688 TI - Optical model for simulation and optimization of luminescent down-shifting layers filled with phosphor particles for photovoltaics. AB - We developed an optical model for simulation and optimization of luminescent down shifting (LDS) layers for photovoltaics. These layers consist of micron-sized phosphor particles embedded in a polymer binder. The model is based on ray tracing and employs an effective approach to scattering and photoluminescence modelling. Experimental verification of the model shows that the model accurately takes all the structural parameters and material properties of the LDS layers into account, including the layer thickness, phosphor particle volume concentration, and phosphor particle size distribution. Finally, using the verified model, complete organic solar cells on glass substrate covered with the LDS layers are simulated. Simulations reveal that an optimized LDS layer can result in more than 6% larger short-circuit current of the solar cell. PMID- 26367689 TI - Structural design of photonic crystal thin film silicon solar cells by sensitivity analysis: Inclusion of electrode absorption. AB - We carry out the structural design of photonic crystals (PCs) using sensitivity analysis for enhancing optical absorption of thin film microcrystalline silicon (MUc-Si) solar cells. In this paper, we employ a model which includes absorption of not only the thin film MUc-Si, but also the transparent conductive oxide and metal back reflector for design accuracy. We carry out structural design for this model using sensitivity analysis which maximizes optical absorption in MUc-Si layer. As a result, we succeed in obtaining the maximum short circuit current density of 25.2 mA/cm2 for thin film (600-nm thick) MUc-Si solar cells (1.4-fold increase compared to the case without a PC). PMID- 26367690 TI - Highly efficient upconversion in Er3+ doped BaY2F8 single crystals: dependence of quantum yield on excitation wavelength and thickness. AB - This manuscript presents a study of the upconversion (UC) in barium yttrium fluoride (BaY2F8) single crystal doped with trivalent erbium ions (Er3+) under excitation of the 4I(13/2) level at three different wavelengths: 1493 nm, 1524 nm and 1556 nm. The resulting UC emission at around 980 nm has been investigated and it has been found that a thickness optimization is required to reach high quantum yield values, otherwise limited by self-absorption losses. The highest external photoluminescence quantum yield (ePLQY) measured in this study was 12.1+/-1.2 % for a BaY2F8:30at%Er3+ sample of thickness 1.75+/-0.01 mm, while the highest internal photoluminescence quantum yield (iPLQY) of 14.6+/-1.5 % was measured in a BaY2F8:20at%Er3+ sample with a thickness of 0.49+/-0.01 mm. Both values were obtained under excitation at 1493 nm and an irradiance of 7.0+/-0.7 Wcm(-2). The reported iPLQY and ePLQY values are among the highest achieved for monochromatic excitation. Finally, the losses due to self-absorption were estimated in order to evaluate the maximum iPLQY achievable by the upconverter material. The estimated iPLQY limit values were ~19%, ~25% and ~30%, for 10%, 20% and 30% Er3+ doping level, respectively. PMID- 26367691 TI - Reconstruction of passive open-path FTIR ambient spectra using meteorological measurements and its application for detection of aerosol cloud drift. AB - Remote sensing of atmospheric aerosols is of great importance to public and environmental health. This research promotes a simple way of detecting an aerosol cloud using a passive Open Path FTIR (OP-FTIR) system, without utilizing radiative transfer models and without relying on an artificial light source. Meteorological measurements (temperature, relative humidity and solar irradiance), and chemometric methods (multiple linear regression and artificial neural networks) together with previous cloud-free OP-FTIR measurements were used to estimate the ambient spectrum in real time. The cloud detection process included a statistical comparison between the estimated cloud-free signal and the measured OP-FTIR signal. During the study we were able to successfully detect several aerosol clouds (water spray) in controlled conditions as well as during agricultural pesticide spraying in an orchard. PMID- 26367692 TI - Sun-tracking optical element realized using thermally activated transparency switching material. AB - We present a proof of concept demonstration of a novel optical element: a light responsive aperture that can track a moving light beam. The element is created using a thermally-activated transparency-switching material composed of paraffin wax and polydimethylsiloxane (PDMS). Illumination of the material with a focused beam causes the formation of a localized transparency at the focal spot location, due to local heating caused by absorption of a portion of the incident light. An application is proposed in a new design for a self-tracking solar collector. PMID- 26367693 TI - Solution processed organic photodetector utilizing an interdiffused polymer/fullerene bilayer. AB - Low dark current (off-current) and high photo current are both essential for a solution processed organic photodetector (OPD) to achieve high photo responsivity. Currently, most OPDs utilize a bulk heterojunction (BHJ) photo active layer that is prepared by the one-step deposition of a polymer:fullerene blend solution. However, the BHJ structure is the main cause of the high dark current in solution processed OPDs. It is revealed that the detectivity and spectral responsivity of the OPD can be improved by utilizing a photo-active layer consisting of an interdiffused polymer/fullerene bilayer (ID-BL). This ID BL is prepared by the sequential solution deposition (SqD) of poly(3 hexylthiophene) (P3HT) and [6,6] phenyl C61 butyric acid methyl ester (PCBM) solutions. The ID-BL OPD is found to prevent undesirable electron injection from the hole-collecting electrode to the ID-BL photo-active layer resulting in a reduced dark current in the ID-BL OPD. Based on dark current and external quantum efficiency (EQE) analysis, the detectivity of the ID-BL OPD is determined to be 7.60 * 10(11) Jones at 620 nm. This value is 3.4 times higher than that of BHJ OPDs. Furthermore, compared to BHJ OPDs, the ID-BL OPD exhibited a more consistent spectral response in the range of 400 - 660 nm. PMID- 26367694 TI - Suppressing lossy-film-induced angular mismatches between reflectance and transmittance extrema: optimum optical designs of interlayers and AR coating for maximum transmittance into active layers of CIGS solar cells: erratum. AB - In my publication [Opt. Express, 22, A167-A178 (2014)], the vertical and horizontal axes on Fig. 6 were mislabeled. Here the corrected figure is presented. PMID- 26367695 TI - Cymbal-shaped phosphor structure for phosphor-converted white LEDs. AB - High efficiency phosphor-converted white light-emitting diodes with superior color uniformity have been investigated. It is proposed that the cymbal-shaped phosphor structure can improve the uniformity of the angle-dependent correlated color temperature (CCT) and also increase the luminous intensity compared to the conventional dispensing phosphor structure. In this experiment, we form the cymbal-shaped structure, which features a bump upon the central surface of the bottom layer, by employing an injection process after the dispensing coating. The upper bump phosphor layer not only enhances the extraction efficiency of lights, but also compensates the difference of the excitation optical path in the dispensing bottom layer between the normal-concentrated forward-scattered blue rays and those emitted with larger angles. This considerably eliminates the "blue center" phenomenon. The CCT deviation have been reduced from 315 K to 120 K using the cymbal-shaped phosphor coating method, and the light extraction efficiency (LEE) is enhanced by 8.5% compared with conventional dispensing phosphor converted white LEDs. This new cymbal-shaped design was verified both experimentally and theoretically. PMID- 26367696 TI - Super-aligned carbon nanotubes patterned sapphire substrate to improve quantum efficiency of InGaN/GaN light-emitting diodes. AB - In this paper, the high performance GaN-based light-emitting diodes (LEDs) on carbon-nanotube-patterned sapphire substrate (CNPSS) by metal-organic chemical vapor deposition (MOCVD) are demonstrated. By studying the mechanism of nucleation, we analyze the reasons of the crystal quality improvement induced by carbon nanotubes (CNTs) in different growth process. Combining with low temperatures photoluminescence (PL) measurements and two-dimensional (2D) finite difference time-domain (FDTD) simulation results, we conclude that the improvement of optical properties and electrical properties of CNPSS mainly originates from the improvement of the internal quantum efficiency (IQE) due to decreased dislocation density during nano-epitaxial growth on CNPSS. Additionally, in order to reduce the light absorption characteristics of CNTs, different time annealing under the oxygen environment is carried out to remove part of CNTs. Under 350 mA current injections, the light output power (LOP) of CNPSS-LED annealed 2 h and 10 h exhibit 11% and 6% enhancement, respectively, compared to that of the CNPSS-LED without annealing. Therefore, high temperature annealing can effectively remove parts of CNTs and further increase the LOP, while overlong annealing time has caused degradation of the quantum well resulting in the attenuation of optical power. PMID- 26367697 TI - Degradation modeling of mid-power white-light LEDs by using Wiener process. AB - The IES standard TM-21-11 provides a guideline for lifetime prediction of LED devices. As it uses average normalized lumen maintenance data and performs non linear regression for lifetime modeling, it cannot capture dynamic and random variation of the degradation process of LED devices. In addition, this method cannot capture the failure distribution, although it is much more relevant in reliability analysis. Furthermore, the TM-21-11 only considers lumen maintenance for lifetime prediction. Color shift, as another important performance characteristic of LED devices, may also render significant degradation during service life, even though the lumen maintenance has not reached the critical threshold. In this study, a modified Wiener process has been employed for the modeling of the degradation of LED devices. By using this method, dynamic and random variations, as well as the non-linear degradation behavior of LED devices, can be easily accounted for. With a mild assumption, the parameter estimation accuracy has been improved by including more information into the likelihood function while neglecting the dependency between the random variables. As a consequence, the mean time to failure (MTTF) has been obtained and shows comparable result with IES TM-21-11 predictions, indicating the feasibility of the proposed method. Finally, the cumulative failure distribution was presented corresponding to different combinations of lumen maintenance and color shift. The results demonstrate that a joint failure distribution of LED devices could be modeled by simply considering their lumen maintenance and color shift as two independent variables. PMID- 26367698 TI - Defects dynamics during ageing cycles of InGaN blue light-emitting diodes revealed by evolution of external quantum efficiency--current dependence. AB - We report in detail the defect dynamics in the active region by monitoring the external quantum efficiency (EQE) - injection current curves, I-V curves, and electroluminescence spectra during the ageing test, under a forward current of 850 mA (85 A/cm2), room temperature. We apply a two-level model to analyze the EQE curves and the electroluminescence spectra. The results suggest that high injection density during the ageing may reduce the density of the Shockley-Reed Hall nonradiative recombination centers and enhance the carrier mobility and diffusion length. The former effect would directly lead to initial surge of EQE, whereas the latter would enhance the effect of extended defects which leads to reduction in peak EQE and increase in EQE droop rate. PMID- 26367699 TI - Inferring inherent optical properties and water constituent profiles from apparent optical properties. AB - The BP09 experiment conducted by the Centre for Maritime Research and Experimentation in the Ligurian Sea in March 2009 provided paired vertical profiles of nadir-viewing radiances L(u)(z) and downward irradiances E(d)(z) and inherent optical properties (IOPs, absorption, scattering and backscattering coefficients). An inversion algorithm was implemented to retrieve IOPs from apparent optical properties (AOPs, radiance reflectance R(L), irradiance reflectance R(E) and diffuse attenuation coefficient K(d)) derived from the radiometric measurements. Then another inversion algorithm was developed to infer vertical profiles of water constituent concentrations, including chlorophyll-a concentration, non-algal particle concentration, and colored dissolved organic matter from the retrieved IOPs based on a bio-optical model. The algorithm was tested on a synthetic dataset and found to give reliable results with an accuracy better than 1%. When the algorithm was applied to the BP09 dataset it was found that good retrievals of IOPs could be obtained for sufficiently deep waters, i.e. for L(u)(z) and E(d)(z) measurements conducted to depths of 50 m or more. This requirement needs to be satisfied in order to obtain a good estimation of the backscattering coefficient. For such radiometric measurements a correlation of 0.88, 0.96 and 0.93 was found between retrieved and measured absorption, scattering and backscattering coefficients, respectively. A comparison between water constituent values derived from the measured IOPs and in-situ measured values, yielded a correlation of 0.80, 0.78, and 0.73 for chlorophyll-a concentration, non-algal particle concentration, and absorption coefficient of colored dissolved organic matter at 443 nm, respectively. This comparison indicates that adjustments to the bio-optical model are needed in order to obtain a better match between inferred and measured water constituent values in the Ligurian Sea using the methodology developed in this paper. PMID- 26367700 TI - Apoptotic induction by pinobanksin and some of its ester derivatives from Sonoran propolis in a B-cell lymphoma cell line. AB - Propolis is a resinous substance produced by honeybees (Apis mellifera) from the selective collection of exudates and bud secretions from several plants. In previous works, we reported the antiproliferative activity of Sonoran propolis (SP) on cancer cells; in addition we suggested the induction of apoptosis after treatment with SP due to the presence of morphological changes and a characteristic DNA fragmentation pattern. Herein, in this study we demonstrated that the antiproliferative effect of SP is induced through apoptosis in a B-cell lymphoma cancer cell line, M12.C3.F6, by an annexin V-FITC/Propidium iodide double labeling. This apoptotic effect of SP resulted to be mediated by modulations in the loss of mitochondrial membrane potential (DeltaPsim) and through activation of caspases signaling pathway (3, 8 and 9). Afterward, in order to characterize the chemical constituents of SP that induce apoptosis in cancer cells, an HPLC-PDA-ESI-MS/MS method followed by a preparative isolation procedure and NMR spectroscopy analysis have been used. Eighteen flavonoids, commonly described in propolis from temperate regions, were characterized. Chrysin, pinocembrin, pinobanksin and its ester derivatives are the main constituents of SP and some of them have never been reported in SP. In addition, two esters of pinobanksin (8 and 13) are described by first time in propolis samples in general. The antiproliferative activity on M12.C3.F6 cells through apoptosis induction was exhibited by pinobanksin (4), pinobanksin-3-O-propanoate (14), pinobanksin-3-O-butyrate (16), pinobanksin-3-O-pentanoate (17), and the already reported galangin (11), chrysin (9) and CAPE. To our knowledge this is the first report of bioactivity of pinobanksin and some of its ester derivatives as apoptosis inducers. Further studies are needed to advance in the understanding of the molecular basis of apoptosis induction by SP and its constituents, as well as the structure-activity relationship of them. PMID- 26367701 TI - Inhalation exposure to ethylene induces eosinophilic rhinitis and nasal epithelial remodeling in Fischer 344 rats. AB - This study investigated the time- and concentration-dependent effects of inhaled ethylene on eosinophilic rhinitis and nasal epithelial remodeling in Fisher 344 rats exposed to 0, 10, 50, 300, or 10,000 ppm ethylene, 6 h/day, 5 days/week for up to 4 weeks. Morphometric quantitation of eosinophilic inflammation and mucous cell metaplasia/hyperplasia (MCM) and nasal mucosal gene expression were evaluated at anatomic sites previously shown to undergo ethylene-induced epithelial remodeling. Serum levels of total IgE, IgG1 and IgG2a were measured to determine if ethylene exposure increased the expression of Th2-associated (IgE and IgG1) relative to Th1-associated (IgG2a) antibody isotypes. Rats exposed to 0 or 10,000 ppm for 1, 3, 5, 10, or 20 days were analyzed to assess the temporal pattern of ethylene-induced alterations in nasal epithelial cell proliferation, morphology and gene expression. Rats exposed to 0, 10, 50, 300, and 10,000 ppm ethylene for 20 days were analyzed to assess concentration-dependent effects on lesion development. Additional rats exposed 4 weeks to 0, 300, or 10,000 ppm ethylene were held for 13 weeks post-exposure to examine the persistence of ethylene-induced mucosal alterations. The data indicate that cell death and reparative cell proliferation were not a part of the pathogenesis of ethylene induced nasal lesions. Enhanced gene expression of Th2 cytokines (e.g., IL-5, IL 13) and chitinase (YM1/2) in the nasal mucosa was much greater than that of Th1 cytokines (e.g., IFNgamma) after ethylene exposure. A significant increase in MCM was measured after 5 days of exposure to 10,000 ppm ethylene and after 20 days of exposure 10 ppm ethylene. Ethylene-induced MCM was reversible after cessation of exposure. No increase in total serum IgE, IgG1 or IgG2a was measured in any ethylene-exposed group. These data do not support involvement of an immune mediated allergic mechanism in the pathogenesis of ethylene-induced nasal lesions in rats. Repeated inhalation of ethylene can induce a local Th2-mediated response in the nasal mucosa of rats, however the mechanisms which induce nasal inflammatory and epithelial responses are yet to be determined. PMID- 26367702 TI - Investigating social inequalities in exposure to drinking water contaminants in rural areas. AB - Few studies have assessed social inequalities in exposure to drinking water contaminants. This study explores this issue in 593 rural municipalities of Quebec, Canada. Quartiles of an ecological composite deprivation index were used as a proxy of socioeconomic status. Total trihalomethanes (TTHMs) and lead were chosen as proxies of chemical drinking water quality. The results show that the majority of deprived rural municipalities apply no treatment to their water (26%) or use a basic treatment (51%), whereas a relative majority of the wealthiest municipalities (40%) use advanced treatment. The proportion of municipalities having important lead (>5 MUg/L) levels is highest in most deprived municipalities. Moreover, most deprived municipalities have a higher risk of high tap lead levels (RR = 1.33; 95%CI: 1.30, 1.36). Conversely, most deprived municipalities have a lower risk of high TTHMs levels (RR = 0.78; 95%CI: 0.69, 0.86). These findings suggest an environmental inequality in drinking water contaminants distribution in rural municipalities. PMID- 26367703 TI - Estimating emissions of PFOS and PFOA to the Danube River catchment and evaluating them using a catchment-scale chemical transport and fate model. AB - Novel approaches for estimating the emissions of perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) to surface waters are explored. The Danube River catchment is used to investigate emissions contributing to riverine loads of PFOS and PFOA and to verify the accuracy of estimates using a catchment scale dynamic fugacity-based chemical transport and fate model (STREAM-EU; Spatially and Temporally Resolved Exposure Assessment Model for European basins). Model accuracy evaluation performed by comparing STREAM-EU predicted concentrations and monitoring data for the Danube and its tributaries shows that the best estimates for PFOS and PFOA emissions in the Danube region are obtained by considering the combined contributions of human population, wealth (based on local gross domestic product (GDP)) and wastewater treatment. Human population alone cannot explain the levels of PFOS and PFOA found in the Danube catchment waters. Introducing wealth distribution information in the form of local GDPs improves emission estimates markedly, likely by better representing emissions resulting from consumer trends, industrial and commercial sources. For compounds such as PFOS and PFOA, whose main sink and transport media is the aquatic compartment, a major source to freshwater are wastewater treatment plants. Introducing wastewater treatment information in the emission estimations also further improves emission estimates. PMID- 26367704 TI - Urban particle size distributions during two contrasting dust events originating from Taklimakan and Gobi Deserts. AB - The dust origins of the two events were identified using HYSPLIT trajectory model and MODIS and CALIPSO satellite data to understand the particle size distribution during two contrasting dust events originated from Taklimakan and Gobi deserts. The supermicron particles significantly increased during the dust events. The dust event from Gobi desert affected significantly on the particles larger than 2.5 MUm, while that from Taklimakan desert impacted obviously on the particles in 1.0-2.5 MUm. It is found that the particle size distributions and their modal parameters such as VMD (volume median diameter) have significant difference for varying dust origins. The dust from Taklimakan desert was finer than that from Gobi desert also probably due to other influencing factors such as mixing between dust and urban emissions. Our findings illustrated the capacity of combining in situ, satellite data and trajectory model to characterize large-scale dust plumes with a variety of aerosol parameters. PMID- 26367705 TI - Quantitative evaluation of noncovalent interactions between polyphosphate and dissolved humic acids in aqueous conditions. AB - As one kind of phosphorus species, polyphosphate (poly-P) is ubiquitous in natural environments, and the potential interactions between poly-P and humic substances in the sediments or natural waters would influence the fate of poly-P in the environments. However, the mechanism of the interactions has not yet been understood clearly. In this work, the characteristics and mechanisms of the interactions between humic acids (HA) and two model poly-P compounds with various chain lengths have been investigated. Results show that a stable polyphosphate-HA complex would be formed through the noncovalent interactions, and hydrogen bond might be the main driving force for the binding process, which might be formed between the proton-accepting groups of poly-P (e.g., PO and P-O(-)) and the oxygen containing functional groups in HA. Our findings implied that the presence of humic substances in natural waters, soils and sediments would influence the potential transport and/or mobility of environmental poly-P. PMID- 26367706 TI - Effects of tropospheric ozone on loblolly pine seedlings inoculated with root infecting ophiostomatoid fungi. AB - Seedlings from four loblolly pine (Pinus taeda L.) families were exposed in open top chambers to charcoal-filtered air (CF), non-filtered air (NF) or air amended with ozone to 2 times ambient (2*). Two of the families used were selected for their tolerance to fungi associated with Southern Pine Decline while two were selected for their susceptibility. Seedlings were treated with five inoculation treatments: no wound (NW), wound only (W), wound + media (WM), Grosmannia huntii (GH) and Leptographium terebrantis (LT). After 118 days of exposure (AOT40 = 31 ppm-hr(-1) for 2* ozone) seedling volume, dry matter, chlorophyll content, water potential and lesions were measured and analyzed using ANOVA procedures. Our results indicate that seedlings selected for their susceptibility to root infecting ophiostomatoid fungi were also more sensitive to ozone. Overall lesion length was greater on seedlings exposed to elevated ozone concentrations but was not specific to either root infecting ophiostomatoid fungi. PMID- 26367707 TI - Joint toxicity of sediment-associated permethrin and cadmium to Chironomus dilutus: The role of bioavailability and enzymatic activities. AB - Pyrethroid insecticides and metals commonly co-occurred in sediment and caused toxicity to benthic organisms jointly. To improve accuracy in assessing risk of the sediments contaminated by insecticides and metals, it is of great importance to understand interaction between the contaminants and reasons for the interaction. In the current study, permethrin and cadmium were chosen as representative contaminants to study joint toxicity of pyrethroids and metals to a benthic invertebrate Chironomus dilutus. A median effect/combination index isobologram was applied to evaluate the interaction between sediment-bound permethrin and cadmium at three dose ratios. Antagonistic interaction was observed in the midges for all treatments. Comparatively, cadmium-dominated group (the ratio of toxicity contribution from permethrin and cadmium was 1:3) showed stronger antagonism than equitoxicity (1:1) and permethrin-dominated groups (3:1). The reasons for the observed antagonism were elucidated from two aspects, including bioavailability and enzymatic activity. The bioavailability of permethrin, expressed as the freely dissolved concentrations in sediment porewater and measured by solid phase microextraction, was not altered by the addition of cadmium, suggesting the change in permethrin bioavailability was not the reason for the antagonism. On the other hand, the activities of metabolic enzymes, glutathione S-transferase and carboxylesterase in the midges which were exposed to mixtures of permethrin and cadmium were significantly higher than those in the midges exposed to permethrin solely. Cadmium considerably enhanced the detoxifying processes of permethrin in the midges, which largely explained the observed antagonistic interaction between permethrin and cadmium. PMID- 26367708 TI - Prenatal nonylphenol exposure, oxidative and nitrative stress, and birth outcomes: A cohort study in Taiwan. AB - Data concerning the effects of prenatal exposures to nonylphenol (NP) and oxidative stress on neonatal birth outcomes from human studies are limited. A total of 146 pregnant women were studied (1) to investigate the association between prenatal NP exposure and maternal oxidative/nitrative stress biomarkers of DNA damage (8-hydroxy-2'-deoxyguanosine (8-OHdG), 8-nitroguanine (8-NO2Gua)) and lipid peroxidation (8-iso-prostaglandin F2alpha (8-isoPF2alpha), 4-hydroxy-2 nonenal-mercapturic acid (HNE-MA)) and (2) to explore the associations among oxidative stress biomarkers, NP exposure, and neonatal birth outcomes, including gestational age, birth weight, length, Ponderal index, and head and chest circumferences. NP significantly increased the 8-OHdG and 8-NO2Gua levels. All infants born to mothers with urinary 8-OHdG levels above the median exhibited a significantly shorter gestational duration (Badjusted = -4.72 days; 95% CI: -8.08 to -1.36 days). No clear association was found between NP levels and birth outcomes. Prenatal 8-OHdG levels might be a novel biomarker for monitoring fetal health related to NP exposure. PMID- 26367710 TI - Iloprost administration in acrodermatitis of Hallopeau complicated by acquired toes syndactyly: a case report and review of the literature. AB - OBJECTIVE: Acrodermatitis Continua of Hallopeau (ACH) is a variant of pustular psoriasis often very difficult to treat. Secondary syndactyly, also called "pseudosyndactyly", is rare and can be a complication of burns, dystrophic epidermolysis bullosa or trauma. If left untreated, joint complications and definitive functional impairments may occur. CASE REPORT: We report a case of a 74-year-old man with acrodermatitis continua of Hallopeau involving the toes and complicated by syndactyly. ACH regression following Iloprost administration was also observed. DISCUSSION: Published studies are mainly limited to case reports only, due to the rarity of the disease. Therefore, there are no clear-cut therapeutic management guidelines available for this chronic and sometimes debilitating disease. ACH is often recalcitrant to the available therapies. Topical and systemic treatments have been described in literature with no long lasting results. CONCLUSIONS: To our knowledge, this is the first report of foot syndactyly associated to ACH. In our patient, ACH symptoms regressed with Iloprost administration: this finding has never been previously described in literature. If confirmed by other clinical experiences, Iloprost could be a further therapeutic option in ACH. PMID- 26367709 TI - Overexpression of AQP3 Modifies the Cell Cycle and the Proliferation Rate of Mammalian Cells in Culture. AB - Abnormal AQP3 overexpression in tumor cells of different origins has been reported and a role for this enhanced AQP3 expression in cell proliferation and tumor processess has been indicated. To further understand the role AQP3 plays in cell proliferation we explore the effect that stable over expression of AQP3 produces over the proliferation rate and cell cycle of mammalian cells. The cell cycle was analyzed by flow cytometry with propidium iodide (PI) and the cell proliferation rate measured through cell counting and BrdU staining. Cells with overexpression of AQP3 (AQP3-o) showed higher proliferation rate and larger percentage of cells in phases S and G2/M, than wild type cells (wt). Evaluation of the cell response against arresting the cell cycle with Nocodazole showed that AQP3-o exhibited a less modified cell cycle pattern and lower Annexin V specific staining than wt, consistently with a higher resistance to apoptosis of AQP3 overexpressing cells. The cell volume and complexity were also larger in AQP3-o compared to wt cells. After transcriptomic analysis, RT-qPCR was performed to highlight key molecules implicated in cell proliferation which expression may be altered by overexpression of AQP3 and the comparative analysis between both type of cells showed significant changes in the expression of Zeb2, Jun, JunB, NF kbeta, Cxcl9, Cxcl10, TNF, and TNF receptors. We conclude that the role of AQP3 in cell proliferation seems to be connected to increments in the cell cycle turnover and changes in the expression levels of relevant genes for this process. Larger expression of AQP3 may confer to the cell a more tumor like phenotype and contributes to explain the presence of this protein in many different tumors. PMID- 26367711 TI - Ascending testis following inguinal hernia repair in children. AB - OBJECTIVE: Failure to replace the testes in the scrotum during hernia repair leads to iatrogenic undescended testes. At other times, the testes may spontaneously move back to the inguinal area after being placed in the scrotum, thus resulting in ascending testes. The cases in this study were assessed. PATIENTS AND METHODS: Records of 910 boys operated due to inguinal hernia were assessed retrospectively. Following hernia repair, the testes were placed in the scrotum. After the operation, all the testes were checked for being in the scrotum. They were called for follow-up after the operation. Their testes were checked for remaining in the scrotum. RESULTS: Ascending testes were detected in 4 (0.43%) of the patients. These patients had scrotal hypoplasia and/or retractile testes. Their age ranged between 1-3 years. Ascending testes were bilateral in 2 patients, and on the right side in 2. Human chorionic gonodotropin (hCG) was initiated in 3 patients. Two of them improved. Two underwent scrotal orchiopexy. CONCLUSIONS: These patients may benefit from hCG in the early postoperative period. Later, scrotal orchiopexy may be needed. Patients who have retractile testes or scrotal hypoplasia in addition to inguinal hernia need orchiopexy together with herniorrhaphy. PMID- 26367712 TI - A paired case-control comparison of ziprasidone on visual sustained attention and visual selective attention in patients with paranoid schizophrenia. AB - OBJECTIVE: Cognitive impairment is one of the main targets of the treatment to schizophrenia.The atypical antipsychotic was proved to improve the cognition function of the patients. There were a few of clinical trials to detect the effect of medicine treatment on attention function. But the respective changes of sustained and selective attention in the patients with treatment of ziprasidone were rarely investigated. This present study was to explore the effect of ziprasidone on visual sustained and selective attention in schizophrenia. PATIENTS AND METHODS: There were 81 patients who were treated with ziprasidone and matched with 81 healthy controls in this open-label trial. The functions were evaluated by Continuous Performance Test (CPT) and Color Word Test (CWT) at baseline and eight weeks later. Between two groups the functions were compared at the two time points, and in patients group those were compared prior to and post treatment. RESULTS: As compared with healthy controls, the functions of the patients were worse. But after 8 weeks treatment of ziprasidone the functions improved in some degree, which were indicated by the change of CPT and CWT indexes. Furthermore, those of patients post treatment were better than prior to treatment. CONCLUSIONS: Patients with paranoid schizophrenia have visual sustained and selective attention deficits. The deficits can be improved partly with ziprasidone treatment. PMID- 26367713 TI - The expression features of serum Cystatin C and homocysteine of Parkinson's disease with mild cognitive dysfunction. AB - OBJECTIVE: To discuss the expression features of serum cystatin C, and homocysteine in patients of Parkinson's disease (PD) with mild cognitive impairment. PATIENTS AND METHODS: Patients with PD from the neurology department of the Central Hospital of Xuzhou from august 2012 to august 2014 were enrolled in this study. The Hoehn-Yahr (H&Y) grading rating scale was used to rate the degree of severity of PD, and the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) rating scale was used to rate and group their cognitive impairment, test the level of the serum cystatin C (CysC) and homocysteine (HCY) and their variations after treatment with vitamin B and folic acid. RESULTS: (1) The CysC and HCY in the PD group was higher than that in the normal control (p<0.05); (2) As the H&Y rating upgraded, the CysC and HCY in the PD group gradually increased with the progression of the disease (p<0.05); (3) The level of CysC and HCY in the PD-mild cognitive impairment (MCI) group increased significantly compared with those in the PD group (p<0.05) The correlation analysis showed that there was significant positive correlation between CysC and HCY. (4) After treatment with vitamin B and folic acid, the CysC, and HCY levels were lower than before, but the grades of the repetition measurement scale, MMSE and MoCA had no significant improvement (p>0.05). CONCLUSIONS: A high level of CysC and HCY might be involved in the development of Parkinson disease. Their expression levels were higher in the PD patients with mild cognitive dysfunction and both showed a remarkably positive correlation. PMID- 26367714 TI - Protective effect of nicotine on the cultured rat basal forebrain neurons damaged by beta-Amyloid (Abeta)25-35 protein cytotoxicity. AB - OBJECTIVE: We sought to investigate the intervention effect of nicotine on beta amyloid (Abeta)25-35 protein cytotoxicity in the rat basal forebrain neurons primary cultures. MATERIALS AND METHODS: For this purpose, freshly isolated rat basal forebrain neurons were cultured for 7 days and then exposed to either Abeta(25-35) or the combination of Abeta(25-35) and nicotine for 48 hours. The effects of Abeta(25-35) and nicotine on neurons morphology, growth status and TrkA expression were evaluated through microscopy, MTT assay, RT-PCR and immunocytochemistry. RESULTS: We found that the exposure of cultured neurons to Abeta(25-35) resulted in remarkable morphological changes. The average process number and length as well as the maximum process length of neurons were significantly decreased as compared with those of control. MTT assay showed that Abeta(25-35) impaired the growth of neurons. Abeta(25-35) also inhibited the expression of TrkA at both mRNA and protein levels. However, the addition of nicotine significantly attenuated these changes, indicating that nicotine could protect the neurons from the cytotoxicity of Abeta(25-35). CONCLUSIONS: Nicotine could be useful for the treatment of Alzheimer's disease through its ability to rescue the neurons from Abeta(25-35) cytotoxicity and the protective effect involved upregulated expression of TrkA receptors. PMID- 26367715 TI - The predictive value of epidemiological characteristics, clinical and laboratory findings in adult lymphadenopathy etiology. AB - OBJECTIVE: Our aim was to determine the presence or absence of malignant etiology in the epidemiological, clinical and laboratory results of patients undergoing lymph node biopsies. PATIENTS AND METHODS: This study was carried out between January 2013 and April 2014. We enrolled a total of 150 adult patients who had lymph node biopsies. 73 of these were females (48.7%) and 77 were males (51.3%). The epidemiological characteristics, clinical and laboratory findings were evaluated and compared with the pathological results. RESULTS: Leukopenia (p=0.05) thrombocytopenia (p=0.03) and increased lactate dehydrogenase levels (p=0.01) were found to be associated with the malignancy. In the cervical, submandibular, axillary and inguinal areas lymphadenopathy was generally seem to be benign while the rate of malignancy was higher in the intra-abdominal and supraclavicular regions. In those cases who had a lymph node index of below 2 there was a higher rate of malignancy (p=0.04). In cases which lymphadenopathy accompanied by splenomegaly has been found associated with malignancy (p=0.009). No association with regards to malignancy was found with the erythrocyte sedimentation rate, C-reactive protein and hepatomegaly. CONCLUSIONS: According to the results of the study five variables including cytopenia, lactate dehydrogenase levels, splenomegaly, lymph node index below 2, intra-abdominal and supraclavicular lymphadenopathy were concluded to be the most suitable means of predicting malignant etiology. PMID- 26367716 TI - Clinicopathologic characteristics of pediatric tuberculous pleural effusion: a retrospective analysis of 112 consecutive cases. AB - OBJECTIVE: The aim of this study was to describe the clinicopathologic characteristics of pediatric tuberculous pleural effusion (TPE) patients to make an accurate diagnosis. PATIENTS AND METHODS: Pediatric TPE patients who admitted to Shandong Provincial Chest Hospital were retrospectively reviewed from March 2006 to April 2015. RESULTS: 112 pediatric TPE patients were enrolled. The mean age was 11.6 +/- 3.2 years. 60 (53.6%) patients were diagnosed as TPE, 40 (35.7%) were TPE+Pulmonary tuberculosis (PTB). 96 (85.7%) patients had fever (> 37 degrees C), 81 (72.3%) had dyspnea, 63 (56.3%) had cough. Radiological test results showed effusions on the right side in 58 patients (51.8%), on the left side in 50 patients (44.6%), and on both sides in 4 patients (3.6%). 6 (5.4%) patients were acid-fast bacilli (AFB) smear-positive. 16 (14.3%) PCR positive patients were identified. 41 (36.6%) TB patients were culture-positive. Almost all effusions (99.1%) had the biologic characteristics of exudates. In 91.2% of the effusions, more than 50% of leukocytes were lymphocytes. Pleural adenosine deaminase (40 U/L) was positive in 74.5% of the patients, and erythrocyte sedimentation rate was raised in 84.1%. CONCLUSIONS: The usefulness of routine microbiological tests to diagnose pleural TB is limited by its poor sensitivity. Further studies should be performed to validate new techs and assays for pediatric TPE. PMID- 26367717 TI - Ebola and blood transfusion: existing challenges and emerging opportunities. AB - OBJECTIVE: The deadly Ebola virus has been first known to mankind since 1976. In the past decades, Ebola outbreaks has often been ignored/neglected as erupted in the rural remote/isolated areas of Africa. The recent 2013-2014 epidemic is the most wide-spread with high incidence rates, morbidity and, mortality in the Ebola history. Eventually, the World Health Organization (WHO) has declared it as a 'Public Health Concern of the International Community'. This scrutiny was conducted to initiate a serious debate on various aspects of Ebola, particularly blood transfusion as an empirical therapeutic modality. METHODS: A search has been performed using the premier scientific databases, WHO documents, and English language search engines. Of 278 potential articles that were identified using a fixed set of criteria, a convenience sample of eighty-two appropriate articles was chosen for this review. RESULTS: The current EBO outbreak is predominantly driven by various confounding risk-factors like: (1) frail health care system, (2) unique cultural and religious customs, (3) huge-shortage of skilled professionals, (4) no licensed therapeutic agents, (5) ill-prepared monitoring and early warning systems, and (6) strained budgets; all these have bolstered this epidemic. As lack of neither specific treatments nor reliable interventions to quickly quell this epidemic, WHO has indorsed 'blood transfusion as an empirical therapeutic modality'. Currently, several clinical trials are underway, particularly the two Ebola candidate vaccines and several antiviral drugs and it has been observed that the initial results are quite promising. However, there are several daunting ethical and practical challenges ahead to stem off this outbreak. CONCLUSIONS: The Ebola-hit poverty stricken West-African countries struggle to contain the outbreak, due to lack of potent therapeutics. Consequently, blood-transfusion could serve as an ideal therapeutic modality to save millions of lives. Therefore, industrialized nations and international agencies must aid them to combat with this catastrophe. Besides, it must warrant further multi-layered interventions and interagency policies, in order to build an Ebola-free safe world in the near future. PMID- 26367718 TI - O blood group as an indicator for abdominal aortic aneurysm. AB - OBJECTIVE: An aortic aneurysm is a general term for an enlargement (dilation) of the aorta to greater than 1.5 times normal size. Abdominal aortic aneurysm (AAA) primarily affects the population older than 50 years, with a prevalence of approximately 5%. There are a few theories about AAA etiology. Interest in the relationship between blood type and vascular disease has been established. The aim of our study is to evaluate distribution of blood-groups among the patients with abdominal aortic aneurysm (AAA) as well as to identify any kind of relationship between blood type and AAA. MATERIALS AND METHODS: The design of our research is combination of retrospective and prospective case-control study in a sample of population of Montenegro. Statistical analysis was performed in SPPS v 20.0, using the chi-square test for independent samples, with the probability level at p < 0.05 as significant, and p < 0.01 as highly significant. RESULTS: O blood group was the most frequent among the examination group (53.11%), and A blood group was the most frequent among group without AAA (43.22%). Presence of AAA in individuals with O blood type was 1.46 higher than for the other blood types. CONCLUSIONS: This finding leads us to suspect that O blood type can be indicator for AAA. PMID- 26367719 TI - Valve replacement for valvular heart disease with giant left ventricle. AB - OBJECTIVE: To discuss early efficacy of the cardiac patient with giant left ventricle underwent valve replacement. PATIENTS AND METHODS: Fifty-five patients, who are suffering cardiac valve disease with giant left ventricle, underwent valve replacement. Among them, sixteen patients underwent aortic valve replacement; thirty patients underwent mitral valve replacement; nine patients underwent double valve replacement. All of them use mechanical heart valve. RESULTS: The number of early death after operation was five. Two patients died of malignant arrhythmia; two died of intractable low cardiac output syndrome; the last one's mechanical valve lost its ability to function after operation and died of respiration-circulation failure after an emergency operation. The death rate was 9%. The remaining 55 patients were cured and their cardiac function was significantly improved. CONCLUSIONS: The definite effective myocardial protection and perfect and detailed preoperative treatment can reduce the possibility of operative complications and death rate of this kind of patients. PMID- 26367720 TI - Evaluation of hand circulation with CardioWaves photoplethysmograph device during Allen test in healthy volunteers. AB - OBJECTIVE: Radial artery occlusion is a potential complication of transradial procedures and its occurrence ranges from 0.8 to 30%. It is virtually always asymptomatic but the functional and sensorial consequences of a long acting hand hypoperfusion could go underestimated. CardioWaves is a novel photoplethysmograh device that allows us to detect the pulse wave amplitude of the blood flowing to the hand. Our objective was to assess in normal subjects the hand blood flow supplied by radial arteries and ulnopalmar arches, respectively, by using CardioWaves device during modified Allen's test (MAT). PATIENTS AND METHODS: MAT was performed on both hands of 60 normal subjects, age ranging 21 to 66 years, without any cardiovascular factor risk. RESULTS: Photoplethysmograh and MAT showed a high positive linear correlation (r=0.93). Despite that, MAT tends to give a higher reading by between 1.05 and 1.6 sec. 11 of 120 readings (9%) by CardioWaves showed values of radial/ulnar pulse amplitude ratio more than mean + 1 SD, suggesting a significant decrease in ulnopalmar arterial circulation when radial blood flow supply would ceased. CONCLUSIONS: The CardioWaves device allows us an accurate reading of the flow because of its independency from respiratory changes. Furthemore, the evaluation of radial and ulnar pulse wave amplitude and the ratio between them would reveal an insufficient blood flow supply by the ulnar artery irrespective of the MAT results. We suggest that their assessment before performing coronary angiography and interventions may reduce potential complication of transradial access. PMID- 26367721 TI - The impact of intravascular ultrasound guidance during drug eluting stent implantation on angiographic outcomes. AB - OBJECTIVE: Major limitation for the use of stent in the treatment of coronary artery disease is development of stent restenosis. The impact of intravascular ultrasound (IVUS) guidance during drug eluting stent (DES) implantation is presently not yet well established. PATIENTS AND METHODS: For the present study, we included 30 patients who received DES with IVUS-guided stenting (Group A) and 30 patients receiving the DES without IVUS-guided stenting (Group B). The patients were evaluated for their ninth month control angiographies and were followed during two years for the development of relevant clinical events after the DES implantations. The angiographic and clinical results were compared between the groups. RESULTS: After the percutaneous intervention, the minimal luminal diameter and net acute gain were significantly increased in Group A in respect to Group B (3.3 +/- 0.34 vs. 2.8 +/- 0.33, p < 0.01). Moreover, the rate for performing post-dilatation following stent implantation was higher in Group A than in Group B (p = 0.01). By contrast, stent restenosis rates were similar between the groups (p > 0.3). CONCLUSIONS: The present results indicate that the use of IVUS for the implantation of DES can increase the success rate of the intervention. The IVUS guidance during DES implantation can be complementary percutaneous intervention, in particularly by detecting the situations that need for post-dilatation. PMID- 26367722 TI - On the changes of NT-proBNP level in children having undergone radical operation of tetralogy of Fallot and the clinical significance. AB - OBJECTIVE: To explore changes of plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) level in children having undergone radical operation of tetralogy of Fallot (TOF) and its clinical significance. PATIENTS AND METHODS: 52 cases of children with TOF hospitalized in our hospital from October 2011 to April 2013 were chosen, and they were all treated with radical operation of TOF. Levels of plasma NT-proBNP in these children were measured before the operation, and 3h, 12h, 48h, 1 week, 1 months, and 3 months after the operation. The cardiac color supersonic diagnostic set was used to examine pulmonary artery transvalvular pressure gradient, right ventricular end-diastolic volume (RVEDV), left ventricular ejection fraction (LVEF), and right ventricular Tei index. RESULTS: (1) 3h after the operation, the level of NT-proBNP gradually rose and reached its peak 48h after the operation, which was markedly higher than the level before the operation (p < 0.01), yet the levels measured 1 month and 3 months after the operation were lower than the level before the operation (p < 0.05). (2) 1 week after the operation, NT-proBNP level, pulmonary artery transvalvular pressure gradient, and RVEDV of the group with right ventricular dysfunction were markedly higher than those of the group with normal right ventricular function (p < 0.05). (3) 3 months after the operation, levels of plasma NT-proBNP of children in the severe reflux group and moderate reflux group were markedly higher than those in the slight reflux group (p < 0.05); levels of plasma NT-proBNP of children in the severe reflux group were markedly higher than those of the slight reflux group (p < 0.05) 1 week or 3 months after the operation. CONCLUSIONS: Changes of the NT proBNP level during early stage after radical operation of children's TOF were in line with changes of the right ventricular function and could be regarded as an objective indicator for evaluating the right ventricular function. PMID- 26367723 TI - Assessment of left atrial functions in cardiac syndrome X. AB - OBJECTIVE: Cardiac syndrome X (CSX) affects left ventricular functions due to myocardial ischaemia. In this study our aim was to determine the changes in left atrial functions in patients with CSX. PATIENTS AND METHODS: One-hundred patients (M/F; 57/43) diagnosed with CSX in whom ischaemia was detected at exercise test and myocardial perfusion scintigrapghy with normal coronary angiogram and control group of 80 subjects (M/F; 40/40) were recruited into the study. In transthoracic echocardiography and tissue doppler echocardiography, left ventricular and atrial functions were recorded. RESULTS: As compared to control group,left ventricular diastolic functions were impaired (E/A; 0.95 +/- 0.18 vs 1.11 +/- 0.29 p < 0.001), left ventricular end-diastolic pressures were increased (E/Em; 8.1 +/- 1.85 vs 6.9 +/- 1.74 p < 0.05), and left atrial maximum volume, left atrial pre-A volume,left atrial minimum volume were increased in patients with CSX. Left atrial conduit volume was significantly decreased in patients with cardiac syndrome. Left atrial passive emptying volume (LAPEV), left atrial active emptying volume (LAAEV) and left atrial total emptying volume (LATEV) were significantly increased in patients with cardiac syndrome X. Left atrial passive ejection fration (LAPEF) was found similar between the study groups.Left atrial active ejection fraction (LAAEF) was found significantly increased (37.85 +/- 11.89 vs 33.60 +/- 9.21; p = 0.009) in patients with CSX. Left atrial total ejection fraction (LATEF) was increased in the group with cardiac syndrome X but it didn't reach statistical significance (60.85 +/- 8.73 vs 58.36 +/- 8.29; p = 0.054). CONCLUSIONS: Left atrial active contractile pump function increase in response to impaired left ventricular diastolic functions in CSX. Increased left atrial pump function represents a compensatory mechanism in patients with CSX. These results point out the importance of maintaining sinus rythm in patients with CSX. PMID- 26367724 TI - Copeptin: a diagnostic factor for critical patients. AB - Copeptin is important in determining the prognosis of the disease, assigning mortality, setting treatment modalities and increasing the patients' chances for survival in life threatening conditions. Any stress factor activating the hypothalamic-pituitary-adrenal (HPA) axis causes an increase in arginine vasopressin (AVP) plasma concentrations also known as antidiuretic hormone (ADH). Copeptin is derived from preprovasopressin along with neurophysin II and AVP. Copeptin is released in an equimolar ratio to AVP. Various studies have shown copeptin to be an independent indicator in determining the prognosis of the disease and assigning mortality. The purpose of this review article was to analyze the advantages of copeptin in patients with life threatening illnesses by reviewing medical data bases. PMID- 26367725 TI - Lack of association between CXCL9 and CXCL10 gene polymorphisms and the outcome of rheumatoid arthritis treatment with methotrexate. AB - OBJECTIVE: Methotrexate (MTX) in low doses is used in the therapy of rheumatoid arthritis (RA). The aim of many studies is to identify factors predicting the outcome of treatment with methotrexate in rheumatoid arthritis. The action of MTX in RA is associated with the inhibition of inflammatory mediators synthesis. CXCL9 and CXCL10 chemokines play the important role in inflammatory response in RA patients. The aim of this study was to examine the association between CXCL9/10 gene polymorphisms and response to therapy of RA patients with MTX. PATIENTS AND METHODS: The study included 422 patients diagnosed with rheumatoid arthritis, treated with MTX in doses 20 mg weekly. Good responders were defined as patients who were receiving MTX and had a DAS28 of <= 2.5 at 6 months of therapy. Poor-responders were defined as patients who were receiving MTX and had a DAS28 of > 2.5. RESULTS: There were not statistically significant associations between studied polymorphisms and the outcome of rheumatoid arthritis treatment with methotrexate. CONCLUSIONS: The results of this study suggest lack of associations between the polymorphisms in CXCL9 and CXCL10 genes and the response to MTX in RA patients. PMID- 26367726 TI - Endoultrasonography (EUS) examination of the esophagus in the diagnosis of esophageal duplication: a case report and a review of a literature. AB - Esophageal duplication cysts are a rare medical entity. In most cases they are located at the level of the distal esophagus. Although our case is not unique, we want to focus on it as a reflection on diagnostic methods. The aim of this article is to show through the report on a case of esophageal duplication treated by us, followed by a review of similar cases in the literature, the utility of EUS in the diagnosis of upper-diaphragmatic and not communicating esophageal duplication. We report a case of a 43 year-old woman. She came to our attention for heartburn and retrosternal sense of space. The patient underwent an endoultrasonography (EUS) examination of the esophagus. The framework put EUS diagnosis of cystic formation of the esophagus (esophageal duplication cysts likely). We demonstrate that only EUS has a correlation with the determination of the pre-operative diagnosis with a statistical significance (p <0.001). In the diagnosis of esophageal not communicating duplication cysts EUS is the most specific diagnostic exam. PMID- 26367727 TI - Delayed diagnosis of cholestatic drug-induced liver injury treated with corticosteroid for adrenal insufficiency secondary to miliary tuberculosis. AB - Drug-induced liver injury (DILI) in a patient with multiple comorbidities is often challenging to diagnose because liver injury can be attributed to multiple disease processes. Delayed treatment of DILI could have fatal consequences and, therefore, understanding the features and risks of DILI is crucial. We report a unique case of a patient who was admitted for severe sepsis of unknown etiology. This patient was later found to have miliary tuberculosis (TB) with associated adrenal insufficiency, complicated by acute cholestatic liver injury. Liver injury fully improved after initiation of corticosteroid for the treatment of adrenal insufficiency. The most likely pathophysiology of acute liver injury was DILI, given the clinical course of liver injury and the liver biopsy result of non-caseating granulomas. Although five different antibiotics including ciprofloxacin, metronidazole, vancomycin, imipenem/cilastatin, and cefepime were provided, the timing of liver injury and pharmacology of each drug imply that ciprofloxacin was the most likely antibiotic causing DILI, given the pharmacology of each antibiotics. This case is unique because miliary TB was complicated by adrenal insufficiency and drug-induced cholestatic liver injury, but acute liver injury was fully reversed after corticosteroid treatment. This implies an immune mediated etiology of DILI, especially ciprofloxacin-induced cholestatic liver injury. DILI is challenging to diagnose in the setting of multiple comorbidities. Therefore, it is crucial that clinicians are to be aware of signs and symptoms of DILI, in that delayed diagnose and treatment may have fatal consequences. PMID- 26367728 TI - Hepatitis C virus-related mixed cryoglobulinemic endocapillary proliferative glomerulonephritis and B-cell non-Hodgkin lymphoma: a case report and literature review. AB - OBJECTIVE: Chronic HCV (hepatitis C virus) infection is recognized as the major cause of mixed cryoglobulinemia. Cryoglobulins continually precipitate and form deposits on the vascular endothelium of small to medium-sized blood vessels, which may progress to vasculitic syndrome. CASE REPORT: A 44-year-old female patient with chronic HCV infection presented with purpuras, edema and proteinuria. Her renal findings included microscopic hematuria, moderate proteinuria and endocapillary proliferative glomerulonephritis (EnPGN) on renal biopsy. Serum cryoglobulins comprised mixed monoclonal cryoglobulins characterized by IgM kappa. The serum protein electrophoresis revealed a monoclonal M protein (9.0%). CD19 and CD20-positive B-cell oligo-monoclonal expansion in the bone marrow was revealed. Rapid relief of the clinical symptoms, the disappearance of proteinuria and a sharp decrease in the HCV viral load were observed in our case after one year of interferon therapy. CONCLUSIONS: HCV infection-associated extrahepatic manifestations are diverse, which may lead to misdiagnosis. This is the first report of HCV-associated cryoglobulinemic EnPGN and B-NHL, which rapidly responded to interferon. PMID- 26367729 TI - Expression of recombinant BMP-7 gene increased ossification activity in the rabbit bone mesenchymal stem cells. AB - OBJECTIVE: The mesenchymal stem cells (MSCs), which were distributed in the bone marrow stroma, become ideal progenitor cells in bone tissue engineering because of their convenient isolation, small injury when obtained, and strong osteogenic capacity. The osteogenic differentiation of MSCs, which is indicated by the increased alkaline phosphatase (ALP) activity and the enhanced accumulation of collagen, could be induced by a strong osteogenic capacity biological factor termed bone morphogenetic protein-7 (BMP-7). Although the chemically synthesized BMP-7 was widely applied to study the osteogenic differentiation of MSCs, transferring and expressing BMP-7 gene in target cells is more desirable, especially for gene therapy, given the advantages and convenience on the stable expression of BMP-7. The aim of this study was to determine whether recombinant BMP-7-expressing MSCs would induce bone formation in vitro. MATERIALS AND METHODS: BMP-7 gene was cloned from human placental tissue to construct a recombinant eukaryotic expression plasmid carrying BMP-7 gene by conjugating with eukaryotic expression vector pcDNA3.1. MSCs were isolated from rabbit bone marrow and cultured in vitro. Then they were divided into 3 groups: pcDNA3.1-BMP-7 transfected, pcDNA3.1-transfected, and untransfected. Human healthy fresh placental tissue was provided by the Department of Gynaecology and Obstetrics, Second Affiliated Hospital of Harbin Medical University. Written informed consent was obtained from the women. One healthy male New Zealand rabbit was provided by the Laboratory Animal Center, Harbin Medical University. RESULTS: A significant increase of ALP activity was detected in the supernatant of pcDNA3.1-BMP-7 transfected MSCs, and the enhanced collagen accumulation, which was inferred by the increased hydroxyproline content and RT-PCR. CONCLUSIONS: These results implied that BMP-7 gene was expressed in MSCs sufficiently and was involved in inducing differentiation of MSCs into osteoblast. PMID- 26367730 TI - The expression of PD-L1 APE1 and P53 in hepatocellular carcinoma and its relationship to clinical pathology. AB - OBJECTIVE: To study the expression of programmed death-ligand1 (PD-L1) in hepatocellular carcinoma and its relationship with clinicopathological characteristics and, prognosis of hepatocellular carcinoma and APE1, P53 protein expression levels. PATIENTS AND METHODS: A total of 128 patients with hepatocellular carcinoma were enrolled in this study. The expression of PD-L1, APE1 and P53 were detected by immunohistochemistry.Use immunohistochemical ABC staining method to detect the expression levels of PD-L1, APE1 and P53 protein in the hepatocellular carcinoma of 128 cases. RESULTS: Positive The positive expression rates levels of PD-L1, APE1, and P53 protein in hepatocellular carcinoma tissues are were 82.03%, 92.19%, and 60.94%. PD-L1 positive expression were significantly associated with clinical stage, The PD-L1 protein has a high expression in patients with I ~ II stage liver cancerHBV infection positive and nonportal vein thrombosis (p=0.041; p=0.030; p=0.014). It is inversely correlated with P53 and PD-L1 expression (correlation coefficient -0.227, p=0.010), and positively correlated with APE1 expression (correlation coefficient 0.189, p=0.032). The expression of PD-L1 is associated with the survival time of patients with hepatocellular carcinoma, and the median survival time of patients with high expression of PD-L1 is ten months. The median survival time of patients with low expression is five months (p=0.001). The relationship between the expression of APE1 and P53 protein and overall survival time of patients with hepatocellular carcinoma has not been found. CONCLUSIONS: The PD-L1 and APE1 expression in hepatocellular carcinoma are related to the level of the expression of P53 protein. The expression state of PD-L1 may be a prognostic factor in hepatocellular carcinoma. PMID- 26367731 TI - Rapamycin inhibits the proliferation of SW1990 pancreatic cancer cell. AB - OBJECTIVE: To study the effect of rapamycin on pancreatic cancer cell proliferation, we designed a serial of experiments in human pancreatic cancer cell line SW1990. MATERIALS AND METHODS: SW1990 cells were treated with different concentrations of rapamycin. Cell proliferation was measured by CCK-8 assay and cell colony formation. Cell cycle and apoptosis was analyzed by flow cytometry. The existence of mTOR signaling pathway was demonstrated by immunocytochemistry. Western-blot and real time-PCR were used to test whether mTOR-signaling pathway was inhibited with rapamycin treatment. RESULTS: Our results showed that rapamycin inhibited the cell colony formation and proliferation (p < 0.05). Rapamycin induced G1 cell cycle arrest (p < 0.05) but not cell apoptosis (p > 0.05). p-mTOR, p-p70S6K and p-4E-BP1 were expressed in the cytoplasm of SW1990 cells and those proteins were significantly reduced with rapamycin (p < 0.05). CONCLUSIONS: Rapamycin inhibits SW1990 pancreatic cancer cell proliferation through inhibiting the activation of mTOR pathway. PMID- 26367732 TI - Caffeine inhibits the growth of glioblastomas through activating the caspase-3 signaling pathway in vitro. AB - OBJECTIVE: To study the effects and associated mechanisms of caffeine on cell viability, cycle dynamics, proliferation and apoptosis both in glioblastoma C6 and U87MG cells. MATERIALS AND METHODS: Cell livability in presence or absence of caffeine was detected by the methyl thiazolyl tetrazolium (MTT) colorimetric assay. Flow cytometric analysis was conducted to investigate the cell cycle dynamics and Cell Counting Kit-8 (CCK-8) was used to further study the proliferation of C6 and U87MG glioblastoma cells after treated with caffeine or DMSO. To study the influence of caffeine on apoptosis of glioblastoma C6 and U87MG cells, the value of apoptosis ratio (AR) was calculated by flow cytometry detection. Western blot analysis was used to detect the expression of apoptosis related factors, including Caspase-3, Cyt-C, Bax and Bcl-2. RESULTS: Caffeine at 1 mM reduced the cell viability of the both rat C6 and human U87MG glioblastoma cells to less than 70%. Flow cytometry detection found that caffeine remarkably arrested the C6 and U87MG cells in G0/G1 phase (C6, U87MG: p<0.01, p<0.05). Nevertheless, the percentage of cells in S phase obviously decreased in the caffeine-treated group, when comparing to that of the normal control (C6, U87MG: p<0.01, p<0.01). CCK-8 assay demonstrated that significant decreases in the number of glioblastoma cells were observed in caffeine treatment group, when comparing to that of the normal control (C6, U87MG: p<0.01, p<0.05). Flow cytometric analysis also found that the application of caffeine induced much higher apoptosis of glioblastoma cells, compared with the normal control (C6, U87MG: p<0.01, p<0.05). Furthermore, caffeine markedly reduced the expression of Bcl-2 (C6, U87MG: p<0.01, p<0.01), and promoted the expression of Cyt-C (C6, U87MG: p<0.05, p<0.01) and Caspase-3 (C6, U87MG: p<0.01, p<0.01), comparing to the normal control. CONCLUSIONS: Caffeine inhibits proliferation and induces apoptosis of C6 and U87MG cells, leading to an imbalance in the ratio of proliferation and apoptosis. The apoptosis might be promoted by the motivation of the caspase-3 signaling pathway, which is induced by the release of Cyt-C as well as the elevated rate of Bax/Bcl-2. PMID- 26367733 TI - Investigation of telomerase activity and apoptosis on invasive ductal carcinoma of the breast using immunohistochemical and Western blot methods. AB - OBJECTIVE: Invasive ductal carcinoma (IDC) comprises the largest group of breast cancers. This study aimed to investigate telomerase activity and apoptosis using immunohistochemical and Western blot methods. PATIENTS AND METHODS: In total, 75 cases that had been diagnosed as IDC and 20 cases that had undergone a freezing procedure were included. The histological sections were stained with Bax, Bcl-2, hTERT and BNIP3. The ages of the patients, as well as their hormonal status and tumour sizes and grades were evaluated, as well as the staining characteristics of the antibodies in question. RESULTS: A decrease in Bcl-2 positivity and an increase in Bax positivity were found immunohistochemically with increasing tumour grades. The data obtained by western blot method showed that Bcl-2 was highest in grade 1 tumours although these results were not statistically significant. The relationship between estrogen and progesterone receptor positivity and Bcl-2 was statistically significant, suggesting there is hormonal control through apoptosis. BNIP3 was found to be decreased with increasing tumour grades. Similarly, BNIP3 was found to be having the lowest value in grade 3 tumours by western blot method. Furthermore, hTERT was found to be increased with increasing tumour grades. In the western blot method, hTERT increased nearly four fold compared to the control. In addition, hTERT, which was seen in very high levels in tumours, may be a helpful cancer marker. Both hTERT and BNIP3 are important markers that can provide information about prognosis. CONCLUSIONS: Big improvements can be achieved in tumour progression control with new treatment modalities that stop telomerase activity and hypoxic cell death. PMID- 26367734 TI - Type 2 diabetes mellitus susceptibility gene TCF7L2 is strongly associated with hyperglycemia in the Saudi Arabia Population of the eastern province of Saudi Arabia. AB - OBJECTIVE: We studied the association of single nucleotide polymorphisms (SNPs) rs7903146, rs12255372 and rs4506565 in type 2 diabetes mellitus (T2DM) susceptibility gene, transcription factor 7 like 2 (TCF7L2) with T2DM among the population of the Eastern Province of Saudi Arabia. PATIENTS AND METHODS: In a case-control study, blood samples were collected from 359 T2DM patients and 351 age and sex-matched normoglycemic controls. Genotyping was done by allele specific PCR assay. RESULTS: Our results revealed a strong association between risk T alleles in variants rs12255372 (OR: G/T=1.4233; T/T=2.0395) and rs4506565 (OR: A/T=1.6066; T/T=3.1301) and T2DM among the Saudi population of the Eastern Province of Saudi Arabia. This is the first time that this association has been identified in a Saudi population. However, a common variant, rs7903146, often found to be associated with T2DM in other populations failed to demonstrate any association to T2DM with the present population. These data further strengthens the hypothesis that Saudi populations might carry a distinct risk allele in T2DM susceptibility gene TCF7L2. CONCLUSIONS: The present results confirm that rs12255372 and rs4506565 variants of TCF7L2 show an association, but not rs7903146, with T2DM for the Saudi population of the Eastern Province of Saudi Arabia. PMID- 26367735 TI - Herbal formulation, DIA-2 and Rosiglitazone ameliorates hyperglycemia and hepatic steatosis in type 2 diabetic rats. AB - DIA-2 is a herbal mixture containing standardized extract of Allium sativum and Lagerstroemia speciosa. Recently we have reported the anti-diabetic effect of DIA 2 in high fat diet (HFD) and streptozotocin (STZ) induced type 2 diabetic (T2D) rats. The purpose of this study was to investigate and compare the effects of DIA 2 with Rosiglitazone (RG) on plasma biomarkers of hepatocellular injury, liver carbohydrate metabolizing enzymes, glycogen content, oxidant/antioxidant status and histopathological changes in T2D rats. ALT and ALP levels were significantly decreased after DIA-2 and RG treatment compared to T2D rats. Total protein and albumin remained unaltered in all the groups. Significant decrease in AST levels were observed after DIA-2 (125 mg/kg) and RG treatment. Hepatic hexokinase activity was significantly increased after RG and DIA-2 treatment and fructose-1, 6-bisphosphatase activity were inversely correlated with hexokinase activity. Hepatic gucose-6-phosphatase activity was significantly (p < 0.05) reduced after DIA-2 (62.5 mg/kg) and RG treatment. Lipid peroxides levels was significantly decreased in the liver of DIA-2 (62.5; p < 0.01 & 125 mg/kg; p < 0.05) treated animals. Hepatic glycogen content (p < 0.05) and antioxidant enzymes [SOD (p < 0.01; 62.5 mg/kg); GPx and GSH (125 mg/kg; p < 0.01)] were significantly increased after DIA-2 treatment. RG treatment on hepatic glycogen, GPx (p < 0.01) and SOD, GSH (p < 0.05) levels were significant when compared to T2D rats. These biochemical parameters were also correlated with histopathological evaluation. The above findings revealed that administration of DIA-2 could ameliorate the biochemical and histopathological changes in liver of T2D rats indicating the protective role of DIA-2 against HFD/STZ induced diabetes. In addition, DIA-2 and RG treatment resulted in amelioration of hepatic steatosis in T2D rats. PMID- 26367736 TI - Effect of silymarin plus vitamin E in patients with non-alcoholic fatty liver disease. A randomized clinical pilot study. AB - OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is an increasingly recognized health problem. Various treatment strategies such as thiazolidinediones, metformin, lipid-lowering agents and antioxidants have been evaluated. So far, no single intervention has convincingly improved liver histology. Experience of using silymarin alone or in combination with other agents in patients with NAFLD is limited in the medical literature. The present study was conducted to evaluate the efficacy of silymarin plus vitamin E in the treatment of NAFLD. PATIENTS AND METHODS: A sample of 36 patients was enrolled. The diagnosis of NAFLD was confirmed by percutaneous liver biopsy. All patients were randomized to one of the following intervention groups: group I: treated with 2 tablets per day of silymarin plus vitamin E (Eurosil 85(r), MEDAS SL) and a lifestyle modification program consisting of hypocaloric diet (1520 kcal, 52% of carbohydrates, 25% of lipids and 23% of proteins) and exercise for 3 months and group II (only with the hypocaloric diet). Anthropometric variables as waist circumference, weight, body mass index (BMI) were measured. Biochemical parameters: Glucose, triglycerides, AST, ALT, GGt levels and insulin resistance (HOMA-IR) were determined under fasting conditions. Non-invasive NAFLD-index were applied before and after the treatments: Fatty liver index (FLI), liver accumulation product (LAP) and NAFLD-Fibrosis score (FS). RESULTS: The mean age was 47.4 +/- 11.2 years old (range 18-67); 22 men and 14 women. In group I, 11 patients (61%) have a NAS-score > 5 and 10 (55.5%) in the group II (NS). Anthropometric parameters decreased after treatment in both groups. Patients in both groups showed a decrease in GGt levels after treatment (group I: 68 IU/L vs. 46.2 +/- 27 IU/L; p < 0.05 and group II 80.5 +/- 46 IU/L vs. 50.3 +/- 27 IU/L; p < 0.05). Only in group II we observed a significant decrease in AST and ALT levels. In both groups, we observed a decrease in: FLI index (group I: 86.2 +/- 19 vs. 76.9 + 20; p < 0.05 and in group II: 85.2 +/- 18 vs. 77.5 +/- 23; p < 0.05), and NAFLD-FS index (group I: -1.6 +/- 1.8 vs. -2.1 +/- 1.5; p < 0.05 and in group II -1 +/- 1.9 vs. -1.5 +/- 2.1; p < 0.05). Patients in group I who did not get a 5% loss of weight also displayed decreased GGt levels, and in the FLI and NAFLD-FS indexes; whereas patients in group II without decrease of 5% by weight showed no improvement in any of the analyzed parameters. CONCLUSIONS: Treatment with silymarin plus vitamin E and a hypocaloric diet ameliorate function hepatic test, and non-invasive NAFLD index. Silymarin can be an alternative valid therapeutic option particularly when other drugs are not indicated or have failed or as a complementary treatment associated with other therapeutic programs. PMID- 26367737 TI - Piceatannol, a natural hydroxylated analog of resveratrol, promotes nitric oxide release through phosphorylation of endothelial nitric oxide synthase in human endothelial cells. AB - OBJECTIVE: Endothelial dysfunction associated with many cardiovascular diseases is largely due to reduced nitric oxide (NO) derived from endothelial NO synthase (eNOS). Piceatannol (trans-3,4,3',5'-tetrahydroxystilbene; Pic) is reported to have cardiovascular therapeutic effects. However, the cellular and molecular mechanisms underlying the cardioprotective effects of Pic are still unclear. Here, we investigated whether Pic could influence endothelial NO release in human umbilical vein endothelial cells (HUVECs). MATERIALS AND METHODS: In HUVECs exposed to Pic, NO production and phosphorylation of eNOS and protein kinase B (Akt) were determined by using a commercially available NO assay kit and Western blot analysis, respectively. RESULTS: Pic stimulated dose- and time-dependent NO production via eNOS phosphorylation. Pic also stimulated dose-dependent phosphorylation of Akt. Interestingly, NO production and eNOS phosphorylation in response to Pic were significantly abolished by the phosphoinositide 3-kinase (PI3K)/Akt inhibitor LY294002. CONCLUSIONS: Pic is capable of inducing eNOS phosphorylation and the subsequent NO release, presumably, by activating PI3K/Akt pathway. The potential efficacy of Pic, a natural hydroxylated analog and a metabolite of resveratrol, may aid in the prevention of cardiovascular diseases characterized by endothelial dysfunction. PMID- 26367739 TI - Dimensional analyses of frontal posed smile attractiveness in Japanese female patients. AB - OBJECTIVE: To identify appropriate dimensional items in objective diagnostic analysis for attractiveness of frontal posed smile in Japanese female patients by comparing with the result of human judgments. MATERIALS AND METHODS: Photographs of frontal posed smiles of 100 Japanese females after orthodontic treatment were evaluated by 20 dental students (10 males and 10 females) using a visual analogue scale (VAS). The photographs were ranked based on the VAS evaluations and the 25 photographs with the highest evaluations were selected as group A, and the 25 photos with the lowest evaluations were designated group B. Then 12 dimensional items of objective analysis selected from a literature review were measured. Means and standard deviations for measurements of the dimensional items were compared between the groups using the unpaired t-test with a significance level of P < .05. RESULTS: Mean values were significantly smaller in group A than in group B for interlabial gap, intervermilion distance, maxillary gingival display, maximum incisor exposure, and lower lip to incisor (P < .05). CONCLUSIONS: Significant differences were observed only in the vertical dimension, not in the transverse dimension. Five of the 12 objective diagnostic items were correlated with human judgments of the attractiveness of frontal posed smile in Japanese females after orthodontic treatment. PMID- 26367738 TI - Chronic Endotoxemia in Subjects with Type-1 Diabetes Is Seen Much before the Onset of Microvascular Complications. AB - BACKGROUND: Lipopolysaccharide (LPS)/Endotoxin is hypothesized to play an important role in chronic inflammation associated with Type-1 diabetes (T1DM) and its complications. Endotoxin core antibodies (EndoCAb), LPS binding protein (LBP) and soluble CD14 (sCD14) act as modulators of LPS induced activation of innate immune system in vivo. For the present study we estimated the levels of LPS and its translocation markers in T1DM subjects with and without microvascular complications (MVC) and correlate them with clinical parameters of T1DM and serum inflammatory cytokine levels (TNF-alpha, IL-6, IL-1beta and GM-CSF). METHODS: A total of 197 subjects (64 normal glucose tolerance (NGT) subjects, 97 T1DM subjects without MVC and 36 with MVC) were included in this study and the levels of serum LPS, its translocation markers and cytokines measured by immunoassays. RESULTS: Compared to NGT, T1DM subjects (both with and without MVC) had significantly higher levels of LPS, reduced levels of LBP and EndoCAb along with significant increase in the levels of IL-1beta, IL-6, TNF-alpha and GM-CSF (p<0.05). No significant change was seen in the levels of these biomarkers between T1DM subjects with and without MVC. CONCLUSIONS: Decreased levels of EndoCAb and LBP suggest sustained endotoxin activity in T1DM subjects even before the onset of microvascular complications. PMID- 26367741 TI - Characteristics of Plantar Loads in Maximum Forward Lunge Tasks in Badminton. AB - BACKGROUND: Badminton players often perform powerful and long-distance lunges during such competitive matches. The objective of this study is to compare the plantar loads of three one-step maximum forward lunges in badminton. METHODS: Fifteen right-handed male badminton players participated in the study. Each participant performed five successful maximum lunges at three directions. For each direction, the participant wore three different shoe brands. Plantar loading, including peak pressure, maximum force, and contact area, was measured by using an insole pressure measurement system. Two-way ANOVA with repeated measures was employed to determine the effects of the different lunge directions and different shoes, as well as the interaction of these two variables, on the measurements. RESULTS: The maximum force (MF) on the lateral midfoot was lower when performing left-forward lunges than when performing front-forward lunges (p = 0.006, 95% CI = -2.88 to -0.04%BW). The MF and peak pressures (PP) on the great toe region were lower for the front-forward lunge than for the right-forward lunge (MF, p = 0.047, 95% CI = -3.62 to -0.02%BW; PP, p = 0.048, 95% CI = -37.63 to -0.16 KPa) and left-forward lunge (MF, p = 0.015, 95% CI = -4.39 to -0.38%BW; PP, p = 0.008, 95% CI = -47.76 to -5.91 KPa). CONCLUSIONS: These findings indicate that compared with the front-forward lunge, left and right maximum forward lunges induce greater plantar loads on the great toe region of the dominant leg of badminton players. The differences in the plantar loads of the different lunge directions may be potential risks for injuries to the lower extremities of badminton players. PMID- 26367740 TI - Functional Divergence of Hsp90 Genetic Interactions in Biofilm and Planktonic Cellular States. AB - Candida albicans is among the most prevalent opportunistic fungal pathogens. Its capacity to cause life-threatening bloodstream infections is associated with the ability to form biofilms, which are intrinsically drug resistant reservoirs for dispersal. A key regulator of biofilm drug resistance and dispersal is the molecular chaperone Hsp90, which stabilizes many signal transducers. We previously identified 226 C. albicans Hsp90 genetic interactors under planktonic conditions, of which 56 are involved in transcriptional regulation. Six of these transcriptional regulators have previously been implicated in biofilm formation, suggesting that Hsp90 genetic interactions identified in planktonic conditions may have functional significance in biofilms. Here, we explored the relationship between Hsp90 and five of these transcription factor genetic interactors: BCR1, MIG1, TEC1, TUP1, and UPC2. We deleted each transcription factor gene in an Hsp90 conditional expression strain, and assessed biofilm formation and morphogenesis. Strikingly, depletion of Hsp90 conferred no additional biofilm defect in the mutants. An interaction was observed in which deletion of BCR1 enhanced filamentation upon reduction of Hsp90 levels. Further, although Hsp90 modulates expression of TEC1, TUP1, and UPC2 in planktonic conditions, it has no impact in biofilms. Lastly, we probed for physical interactions between Hsp90 and Tup1, whose WD40 domain suggests that it might interact with Hsp90 directly. Hsp90 and Tup1 formed a stable complex, independent of temperature or developmental state. Our results illuminate a physical interaction between Hsp90 and a key transcriptional regulator of filamentation and biofilm formation, and suggest that Hsp90 has distinct genetic interactions in planktonic and biofilm cellular states. PMID- 26367743 TI - Correction: Synoviocyte Derived-Extracellular Matrix Enhances Human Articular Chondrocyte Proliferation and Maintains Re-Differentiation Capacity at Both Low and Atmospheric Oxygen Tensions. PMID- 26367742 TI - Integrative Analysis of mRNA and miRNA Expression Profiles of the Tuberous Root Development at Seedling Stages in Turnips. AB - The tuberous root of Brassica rapa L. (turnip) is an important modified organ for nutrition storage. A better understanding of the molecular mechanisms involved in the process of tuberous root development is of great value in both economic and biological context. In this study, we analyzed the expression profiles of both mRNAs and miRNAs in tuberous roots at an early stage before cortex splitting (ES), cortex splitting stage (CSS), and secondary root thickening stage (RTS) in turnip based on high-throughput sequencing technology. A large number of differentially expressed genes (DEGs) and several differentially expressed miRNAs (DEMs) were identified. Based on the DEG analysis, we propose that metabolism is the dominant pathway in both tuberous root initiation and secondary thickening process. The plant hormone signal transduction pathway may play a predominant role in regulating tuberous root initiation, while the starch and sucrose metabolism may be more important for the secondary thickening process. These hypotheses were partially supported by sequential DEM analyses. Of all DEMs, miR156a, miR157a, and miR172a exhibited relatively high expression levels, and were differentially expressed in both tuberous root initiation and the secondary thickening process with the expression profiles negatively correlated with those of their target genes. Our results suggest that these miRNAs play important roles in tuberous root development in turnips. PMID- 26367746 TI - Update on hyaluronic acid fillers for facial rejuvenation. AB - Injectable soft tissue filler procedures are becoming increasingly important for rejuvenating the aging face. The variety of available dermal fillers is increasing, and an understanding of their individual characteristics allows optimal outcomes. We provide an overview of the dermal fillers that were approved by the US Food and Drug Administration over the last 5 years. PMID- 26367744 TI - Ergot Alkaloids (Re)generate New Leads as Antiparasitics. AB - Praziquantel (PZQ) is a key therapy for treatment of parasitic flatworm infections of humans and livestock, but the mechanism of action of this drug is unresolved. Resolving PZQ-engaged targets and effectors is important for identifying new druggable pathways that may yield novel antiparasitic agents. Here we use functional, genetic and pharmacological approaches to reveal that serotonergic signals antagonize PZQ action in vivo. Exogenous 5-hydroxytryptamine (5-HT) rescued PZQ-evoked polarity and mobility defects in free-living planarian flatworms. In contrast, knockdown of a prevalently expressed planarian 5-HT receptor potentiated or phenocopied PZQ action in different functional assays. Subsequent screening of serotonergic ligands revealed that several ergot alkaloids possessed broad efficacy at modulating regenerative outcomes and the mobility of both free living and parasitic flatworms. Ergot alkaloids that phenocopied PZQ in regenerative assays to cause bipolar regeneration exhibited structural modifications consistent with serotonergic blockade. These data suggest that serotonergic activation blocks PZQ action in vivo, while serotonergic antagonists phenocopy PZQ action. Importantly these studies identify the ergot alkaloid scaffold as a promising structural framework for designing potent agents targeting parasitic bioaminergic G protein coupled receptors. PMID- 26367745 TI - What does empathy contribute in this age of science and technology? PMID- 26367747 TI - Evaluating endoleaks in the dermatology office. AB - We report the case of a 69-year-old woman who was referred to our dermatology office by her primary care physician for evaluation of a subcutaneous mass overlying the right mid sternum, which was a suspected lipoma. The mass was asymptomatic and had been present for approximately 2 weeks. The patient had undergone an aortic valve replacement approximately 2.5 years prior for treatment of an ascending aortic aneurysm. Physical examination revealed a mass located at the site of the thoracotomy scar. She was referred for an ultrasound and computed tomography angiography. Results of computed tomography angiography were consistent with a type V endoleak, and the patient was then referred to a cardiothoracic surgeon for treatment. Our case represents an unusual entity for presentation at a dermatology clinic, but endoleaks can have dire consequences if they are not recognized and treated appropriately. Dermatologists should be aware of the clinical presentation of endoleaks and this article explains the causes. PMID- 26367748 TI - How to teach the potassium hydroxide preparation: a disappearing clinical art form. AB - Using potassium hydroxide (KOH) preparations in the diagnosis of superficial fungal infections is a technique that has been handed down from teacher to apprentice for more than 100 years. The technique is simple, accurate, and inexpensive; however, there is reason to believe it is falling to the wayside in favor of empiric treatment, especially in primary care settings. To continue the use of this valuable diagnostic aid, a system of teaching the KOH preparation to the next generation of physicians (ie, medical students, residents) is proposed with emphasis on facilitating the process by storing viable skin samples infected with dermatophytes for long periods of time. This technique obviates the need to find suitably infected patients before each teaching laboratory. This technique also is appropriate to refresh the skills of practicing physicians as they prepare for point-of-care testing assessments. PMID- 26367749 TI - Epidermodysplasia verruciformis: successful treatment with squaric acid dibutylester. AB - Epidermodysplasia verruciformis (EV) is a rare disorder characterized by disseminated cutaneous warts in predisposed patients who are highly susceptible to genus beta-papillomavirus infections. We present the case of a 40-year-old lymphocytopenic woman with a balanced chromosomal translocation and a 25-year history of refractory EV that was successfully treated with squaric acid dibutylester (SADBE) contact immunotherapy. PMID- 26367750 TI - Onychomatricoma: an often misdiagnosed tumor of the nails. AB - Onychomatricoma is a subungual tumor that is clinically characterized by banded or diffuse thickening, yellowish discoloration, splinter hemorrhages, and transverse overcurvature of the nail plate. It is often and easily misdiagnosed because the condition is not well known and rarely has been described. We report the case of a 45-year-old man with a subungual tumor on the right index finger that fulfills the criteria of onychomatricoma. PMID- 26367751 TI - The use of sodium sulfacetamide in dermatology. AB - Sodium sulfacetamide is effective in the management of a variety of inflammatory facial dermatoses and often is used in combination with sulfur for a synergistic effect. Adverse effects from sodium sulfacetamide are rare and generally are limited to mild application-site reactions. This agent is contraindicated in any patient with known hypersensitivity to sulfonamides. PMID- 26367752 TI - Stratum corneum absorption kinetics of 2 potent topical corticosteroid formulations: a pilot study. AB - Fluocinonide and halcinonide are class II topical corticosteroids that are indicated for the relief of inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses and generally are applied to affected skin at least twice daily. This pilot study compared the absorption kinetics of cream formulations of fluocinonide and halcinonide in the stratum corneum within a 9 hour period following application. A dermal tape-stripping protocol was used to quantify corticosteroid concentration at 6 sequential depths in the skin of 4 sites on the forearm. Halcinonide and fluocinonide were extracted from the strips and concentrations were measured using liquid chromatography-mass spectrometry. Results demonstrated the immediate absorption of fluocinonide and halcinonide into the stratum corneum within 1 hour of application followed by a sustained release of halcinonide and a steady decline of fluocinonide after peaking. PMID- 26367753 TI - Trichilemmoma. PMID- 26367754 TI - What is your diagnosis? Verrucous carcinoma. PMID- 26367755 TI - Diffuse crusting of the skin. PMID- 26367756 TI - Round purple erythematous tumors. PMID- 26367757 TI - Verrucous carcinoma on the lower extremities. PMID- 26367758 TI - Linear scleroderma associated with neurofibromatosis type I. PMID- 26367759 TI - Nodular scleroderma in a patient with chronic hepatitis C virus infection: a coexistent or causal infection? AB - Nodular scleroderma is a rare form of scleroderma that may occur systemically or locally. The pathogenesis of this variant is unknown. We report the case of a 63 year-old woman with systemic scleroderma and chronic hepatitis C virus (HCV) infection who had numerous papules and nodules on the neck and trunk. Skin biopsies from her lesions revealed characteristic findings of scleroderma. This case not only depicts the rare entity of nodular scleroderma but demonstrates the association of HCV infection with systemic autoimmune diseases such as scleroderma. PMID- 26367760 TI - Perianal North American blastomycosis. AB - Cutaneous North American blastomycosis most often results from the hematogenous spread of Blastomyces dermatitidis following pulmonary infection. Cutaneous lesions, which may be either verrucous or ulcerative plaques, commonly occur on or around orifices contiguous to the respiratory tract. We report the case of a 57-year-old man with cutaneous North American blastomycosis who presented with a well-demarcated, firm, moist, verrucous perianal plaque 4 months following the onset of a prolonged upper respiratory tract infection. Dissemination of B dermatitidis to the perianal skin is rare, but North American blastomycosis should be considered in the broad differential diagnosis of perianal lesions in any patients who have lived in or traveled to endemic regions. PMID- 26367761 TI - Recurrent pyogenic granuloma with a satellite lesion. AB - Pyogenic granuloma (PG) is a tumorlike growth of the oral mucosa or skin that is considered to be an exaggerated conditioned response to minor trauma. It usually is painless, bleeds easily, and is considered to be nonneoplastic in nature. Pyogenic granuloma predominantly occurs in the second decade of life, mostly among young adult females. Clinically, it is a smooth or lobulated exophytic lesion manifesting as small, red, erythematous papules on a pedunculated or sometimes sessile base that usually is hemorrhagic. We report the case of 30-year old woman who presented with a PG in the anterior palatal region during pregnancy that recurred with a satellite lesion 1 year following surgical excision. PMID- 26367762 TI - Don't forget about syphilis. AB - Syphilis has extremely variable manifestations that produce an extremely broad differential diagnosis. Care must be taken to consider syphilis in dermatologic and other systemic disorders as is relevant. PMID- 26367763 TI - Dry scaly rash. PMID- 26367764 TI - Bilateral auricular swelling: marginal zone lymphoma with cutaneous involvement. PMID- 26367765 TI - Sweet syndrome presenting with an unusual morphology. PMID- 26367766 TI - Exposure of chick embryos to cadmium changes the extra-embryonic vascular branching pattern and alters expression of VEGF-A and VEGF-R2. AB - Cadmium (Cd) has several industrial applications, and is found in tobacco products, a notable source of human exposure. Vascular endothelial cells are key targets of Cd toxicity. Here, we aim to quantify the alteration to vascular branching pattern following Cd exposure in the chick extra-embryonic membrane (EEM) using fractal analysis, and explore molecular cues to angiogenesis such as VEGF-A and VEGF-R2 expression following Cd treatment. Chicken embryos were incubated for 60 h to Hamburger-Hamilton developmental stage 16-17, then explanted and treated with 50 MUL of 50 MUmol cadmium acetate (CdAc) or an equivalent volume of equimolar sodium acetate (NaAc). Images of embryos and their area vasculosa (AV) were captured and analyzed at 4 different time points (4, 8, 24 and 48 h) following treatment. Vascular branching in the AV was quantified using its fractal dimension (Df), estimated using a box counting method. Gallinaceous VEGF ELISA was used to measure the VEGF-A concentration in the EEM following treatment, with determination of the relative expression of VEGF-A and VEGF-R2 using quantitative real-time RT-PCR. Vascular branching increased monotonically in the control group at all time points. The anti-angiogenic effect of Cd exposure on the AV was reflected by a significant reduction in Df when compared with controls. Df was more markedly reduced in cultures with abnormal embryos. The expression of VEGF-A protein, and VEGF-A and VEGF-R2 mRNA were reduced in Cd-exposed EEMs. Both molecules contribute to growth, vessel sprouting and branching processes, which supports our findings using fractal analysis. PMID- 26367767 TI - Prenatal caffeine exposure induced a lower level of fetal blood leptin mainly via placental mechanism. AB - It's known that blood leptin level is reduced in intrauterine growth retardation (IUGR) fetus, and placental leptin is the major source of fetal blood leptin. This study aimed to investigate the decreased fetal blood leptin level by prenatal caffeine exposure (PCE) and its underlying placental mechanisms. Pregnant Wistar rats were intragastrically administered caffeine (30-120 mg/kg day) from gestational day 9 to 20. The level of fetal serum leptin and the expression of placental leptin-related genes were analyzed. Furthermore, we investigated the molecular mechanism of the reduced placental leptin's expression by treatment with caffeine (0.8-20 MUM) in the BeWo cells. In vivo, PCE significantly decreased fetal serum leptin level in caffeine dose-dependent manner. Meanwhile, placental mRNA expression of adenosine A2a receptor (Adora2a), cAMP-response element binding protein (CREB), a short-type leptin receptor (Ob Ra) and leptin was reduced in the PCE groups. In vitro, caffeine significantly decreased the mRNA expression of leptin, CREB and ADORA2A in concentration and time-dependent manners. The addition of ADORA2A agonist or adenylyl cyclase (AC) agonist reversed the inhibition of leptin expression induced by caffeine. PCE induced a lower level of fetal blood leptin, which the primary mechanism is that caffeine inhibited antagonized Adora2a and AC activities to decreased cAMP synthesis, thus inhibited the expression of the transcription factor CREB and target gene leptin in the placenta. Meantime, the reduced transportation of maternal leptin by placental Ob-Ra also contributed to the reduced fetal blood leptin. Together, PCE decreased fetal blood leptin mainly via reducing the expression and transportation of leptin in the placenta. PMID- 26367768 TI - Unusual presentation of endometriosis with haemorrhagic ascites - A case report. PMID- 26367769 TI - Investigating Parenting Stress across Pediatric Health Conditions - A Systematic Review. AB - The stress parenting responsibilities place on parents increases in situations involving pediatric illness, and therefore can potentially interfere with the normal family life. The present review examines sources of parenting stress across a wide spectrum of illnesses, using three illness groups as exemplars: Congenital heart disease, pediatric cancer, and Autism Spectrum Disorder. A systematic review of the literature using PubMed, CINAHL, Scopus, and PsycINFO databases yielded 66 observational studies investigating sources of parenting stress in parents of young children with congenital heart defects, cancer, and Autism Spectrum Disorder. Quality assessment, using the STROBE and COREQ quality indexes, was further conducted for the included studies. Stressors were categorized, and then analyzed in light of the diagnostic characteristics of the populations in focus. Findings indicate that parents across all illness groups experience increased levels of parenting stress. Several categories were identified in accordance to the parenting stress model as follows: illness related factors, parental factors, child characteristics, familial factors, and social factors. Further analysis has revealed distinct parental concerns within the groups deriving from the diagnostics, care demands, or social responses specific to each group. Theoretical and practical implications for Family-Systems Nursing Practice were further discussed. Future research and assessment of parenting stress should account for the illness course and address family needs within the specific context of the illness. PMID- 26367770 TI - Tracheal Atresia with Segmental Esophageal Duplication: An Unusual Anatomic Arrangement. AB - An unusual anatomic configuration of segmental tracheal agenesis/atresia with esophageal duplication on autopsy in a fetus that demised in utero at 29 weeks is reported. The mother was scanned initially for a cardiac anomaly at 20 weeks and on follow-up scan at 27 weeks had polyhydramnios and underwent amnioreduction. The final autopsy diagnosis was vertebral, ano-rectal, cardiac, tracheoesophageal, renal, and limb malformations (VACTERL). We discuss the autopsy findings along with the embryological mechanisms and compare the configuration with Floyd's classification for tracheal agenesis. The difficulties in prenatal diagnosis are discussed. PMID- 26367771 TI - A comparative evaluation of different types of microbial electrolysis desalination cells for malic acid production. AB - The aim of this study was to investigate different microbial electrolysis desalination cells for malic acid production. The systems included microbial electrolysis desalination and chemical-production cell (MEDCC), microbial electrolysis desalination cell (MEDC) with bipolar membrane and anion exchange membrane (BP-A MEDC), MEDC with bipolar membrane and cation exchange membrane (BP C MEDC), and modified microbial desalination cell (M-MDC). The microbial electrolysis desalination cells performed differently in terms of malic acid production and energy consumption. The MEDCC performed best with the highest malic acid production rate (18.4 +/- 0.6 mmol/Lh) and the lowest energy consumption (0.35 +/- 0.14 kWh/kg). The best performance of MEDCC was attributable to the neutral pH condition in the anode chamber, the lowest internal resistance, and the highest Geobacter percentage of the anode biofilm population among all the reactors. PMID- 26367772 TI - Magnetic resonance-guided high-intensity focused ultrasound for uterine fibroids: Mid-term outcomes of 36 patients treated with the Sonalleve system. AB - OBJECTIVES: This study sought to assess the mid-term efficacy of magnetic resonance-guided high-intensity focused ultrasound (MRgFUS) (Sonalleve system) for uterine fibroids. METHODS: We retrospectively included patients treated by MRgFUS controlled by real-time MR-thermometry. Clinical efficacy was defined as the minimum reduction of ten points in the Transformed Symptom Severity Score (tSSS) without additional treatment. Fibroid volumes were assessed at 6 months, and patients were contacted to assess mid-term efficacy using tSSS. RESULTS: Thirty-six patients were included; 22 patients (61.1%) exhibited clinical efficacy with a mean follow-up duration of 21.4 (95%CI: 16.3-26.5) months. In addition, the tSSS mean decreased significantly from 42.8 +/- 16 to 25.4 +/- 18 (p < 0.0001). MRgFUS exhibited a preferential effect on menorrhagia (p = 0.001) and symptoms related to pelvic heaviness and swelling (p = 0.004). The volume reduction was 27% (p < 0.001) and was correlated with the non-perfused volume (NPV) after treatment (r = 0.373; p = 0.028). Cumulative re-intervention rates (surgery or uterine artery embolisation) at 12 months, 18 months and 24 months were 2.8%, 8.5% and 21.6%, respectively. No serious adverse events were reported. Two pregnancies occurred during the follow-up period. CONCLUSIONS: Treatment of uterine fibroids by MRgFUS is efficient and results in low morbidity and satisfactory clinical efficacy with a mean follow-up of 21.4 months. PMID- 26367774 TI - Expression of Concern: Protein Under-Wrapping Causes Dosage Sensitivity and Decreases Gene Duplicability. PMID- 26367773 TI - Uncovering Direct Targets of MiR-19a Involved in Lung Cancer Progression. AB - Micro RNAs (miRNAs) regulate the expression of target genes posttranscriptionally by pairing incompletely with mRNA in a sequence-specific manner. About 30% of human genes are regulated by miRNAs, and a single miRNA is capable of reducing the production of hundreds of proteins by means of incomplete pairing upon miRNA mRNA binding. Lately, evidence implicating miRNAs in the development of lung cancers has been emerging. In particular, miR-19a, which is highly expressed in malignant lung cancer cells, is considered the key miRNA for tumorigenesis. However, its direct targets remain underreported. In the present study, we focused on six potential miR-19a target genes selected by miRNA target prediction software. To evaluate these genes as direct miR-19a target genes, we performed luciferase, pull-down, and western blot assays. The luciferase activity of plasmids with each miR-19a-binding site was observed to decrease, while increased luciferase activity was observed in the presence of anti-miR-19a locked nucleic acid (LNA). The pull-down assay showed biotinylated miR-19a to bind to AGO2 protein and to four of six potential target mRNAs. Western blot analysis showed that the expression levels of the four genes changed depending on treatment with miR-19a mimic or anti-miR-19a-LNA. Finally, FOXP1, TP53INP1, TNFAIP3, and TUSC2 were identified as miR-19a targets. To examine the function of these four target genes in lung cancer cells, LK79 (which has high miR-19a expression) and A549 (which has low miR-19a expression) were used. The expression of the four target proteins was higher in A549 than in LK79 cells. The four miR-19a target cDNA expression vectors suppressed cell viability, colony formation, migration, and invasion of A549 and LK79 cells, but LK79 cells transfected with FOXP1 and TP53INP1 cDNAs showed no difference compared to the control cells in the invasion assay. PMID- 26367775 TI - Trials of Improved Practices (TIPs) to Enhance the Dietary and Iron-Folate Intake during Pregnancy- A Quasi Experimental Study among Rural Pregnant Women of Varanasi, India. AB - BACKGROUND: Behavior Change Communications (BCC) play a decisive role in modifying socio-cultural norms affecting the perception and nutritional practices during pregnancy. OBJECTIVE: To examine the effectiveness of 'Trials of Improved Practices' (TIPs) on dietary and iron-folate intake during pregnancy. DESIGN: Community based quasi experimental study with a control group. SETTING: Four villages of Chiraigaon Community Development Block of Varanasi, India from May 2010 and recruited from August 2010. End line assessment, after 12 weeks of intervention, was completed in April 2011. PARTICIPANTS: Pregnant women in 13-28 weeks of gestation. INTERVENTION: TIPs was implemented in addition to ongoing essential obstetric care services in two villages through 3 home (assessment, negotiation and evaluation) visits and only assessment and evaluation visits in the other two control villages. Interpersonal communication, endorsing the active participation of family members and home based reminder materials were the TIPs based strategies. The effect of TIPs was assessed by comparing key outcome variables at baseline and after 12 weeks of intervention. OUTCOME MEASURES: Hemoglobin%, anemia prevalence, weight gain, compliance for iron-folate supplementation and dietary intake of calorie, protein, calcium and iron. RESULTS: A total of 86 participants completed the study. At the end, mean hemoglobin levels were 11.5+/-1.24 g/dl and 10.37+/-1.38 g/dl in the TIPs and control groups, respectively. The prevalence of anemia reduced by half in TIPs group and increased by 2.4% in the control group. Weight gain (grams/week) was significantly (p<0.01) higher in TIPs group (326.9+/-91.8 vs. 244.6+/-97.4). More than 85% of the PW in TIPs group were compliant for Iron-folate and only 38% were compliant among controls. The mean intake of protein increased by 1.78gm in intervention group and decreased by 1.81 gm in controls (p<0.05). More than two thirds of PW in TIPs group were taking one extra meal and only one third of controls were doing the same. CONCLUSION: TIPs found to be an effective approach to improve the nutritional status of pregnant women in the study area. TIPs strategy could be further explored on larger sample representing different socio cultural and geographical areas. TRIAL REGISTRATION: Clinical Trial Registry of India CTRI/2015/02/005517. PMID- 26367777 TI - Tropane and ergot alkaloids in grain-based products for infants and young children in the Netherlands in 2011-2014. AB - An LC-MS/MS multi-method was developed to simultaneously quantify ergot alkaloids (EAs) and tropane alkaloids (TAs) in 113 cereal-based food for infants and young children. To assess yearly variation, samples were collected in 2011, 2012 and 2014. EAs were detected in 54% and TAs in 22% of the samples. Mean EA levels in the three sampling years were 10.6, 6.2 and 8.6 ug kg(-1), respectively (maximum: 115.4 ug kg(-1)), indicating that exposure to EAs would not have exceeded the health-based guidance values set by EFSA in 2012. Mean TA levels were 3.9, 2.4 and 0.4 ug kg(-1), respectively (maximum: 80.8 ug kg(-1)). The acute reference dose for TAs, derived by EFSA in 2013, would have been exceeded by young children when consuming some of the products sampled in 2011-2012. TA levels had decreased drastically in 2014, possibly due to measures taken by producers as response to the EFSA Opinion. PMID- 26367776 TI - Dysbiosis in the Gut Microbiota of Patients with Multiple Sclerosis, with a Striking Depletion of Species Belonging to Clostridia XIVa and IV Clusters. AB - The pathogenesis of multiple sclerosis (MS), an autoimmune disease affecting the brain and spinal cord, remains poorly understood. Patients with MS typically present with recurrent episodes of neurological dysfunctions such as blindness, paresis, and sensory disturbances. Studies on experimental autoimmune encephalomyelitis (EAE) animal models have led to a number of testable hypotheses including a hypothetical role of altered gut microbiota in the development of MS. To investigate whether gut microbiota in patients with MS is altered, we compared the gut microbiota of 20 Japanese patients with relapsing-remitting (RR) MS (MS20) with that of 40 healthy Japanese subjects (HC40) and an additional 18 healthy subjects (HC18). All the HC18 subjects repeatedly provided fecal samples over the course of months (158 samples in total). Analysis of the bacterial 16S ribosomal RNA (rRNA) gene by using a high-throughput culture-independent pyrosequencing method provided evidence of a moderate dysbiosis in the structure of gut microbiota in patients with MS. Furthermore, we found 21 species that showed significant differences in relative abundance between the MS20 and HC40 samples. On comparing MS samples to the 158 longitudinal HC18 samples, the differences were found to be reproducibly significant for most of the species. These taxa comprised primarily of clostridial species belonging to Clostridia clusters XIVa and IV and Bacteroidetes. The phylogenetic tree analysis revealed that none of the clostridial species that were significantly reduced in the gut microbiota of patients with MS overlapped with other spore-forming clostridial species capable of inducing colonic regulatory T cells (Treg), which prevent autoimmunity and allergies; this suggests that many of the clostridial species associated with MS might be distinct from those broadly associated with autoimmune conditions. Correcting the dysbiosis and altered gut microbiota might deserve consideration as a potential strategy for the prevention and treatment of MS. PMID- 26367778 TI - The key kinematic determinants of undulatory underwater swimming at maximal velocity. AB - The optimisation of undulatory underwater swimming is highly important in competitive swimming performance. Nineteen kinematic variables were identified from previous research undertaken to assess undulatory underwater swimming performance. The purpose of the present study was to determine which kinematic variables were key to the production of maximal undulatory underwater swimming velocity. Kinematic data at maximal undulatory underwater swimming velocity were collected from 17 skilled swimmers. A series of separate backward-elimination analysis of covariance models was produced with cycle frequency and cycle length as dependent variables (DVs) and participant as a fixed factor, as including cycle frequency and cycle length would explain 100% of the maximal swimming velocity variance. The covariates identified in the cycle-frequency and cycle length models were used to form the saturated model for maximal swimming velocity. The final parsimonious model identified three covariates (maximal knee joint angular velocity, maximal ankle angular velocity and knee range of movement) as determinants of the variance in maximal swimming velocity (adjusted r2 = 0.929). However, when participant was removed as a fixed factor there was a large reduction in explained variance (adjusted r2 = 0.397) and only maximal knee joint angular velocity continued to contribute significantly, highlighting its importance to the production of maximal swimming velocity. The reduction in explained variance suggests an emphasis on inter-individual differences in undulatory underwater swimming technique and/or anthropometry. Future research should examine the efficacy of other anthropometric, kinematic and coordination variables to better understand the production of maximal swimming velocity and consider the importance of individual undulatory underwater swimming techniques when interpreting the data. PMID- 26367779 TI - A novel tool to standardize rheology testing of molten polymers for pharmaceutical applications. AB - Melt rheology provides information about material properties that are of great importance for equipment design and simulations, especially for novel pharmaceutical manufacturing operations, including extrusion, injection molding or 3d printing. To that end, homogeneous samples must be prepared, most commonly via compression or injection molding, both of which require costly equipment and might not be applicable for shear- and heat-sensitive pharmaceutical materials. Our study introduces a novel vacuum compression molding (VCM) tool for simple preparation of thermoplastic specimens using standard laboratory equipment: a hot plate and a vacuum source. Sticking is eliminated by applying polytetrafluoroethylene (PTFE) coated separation foils. The evacuation of the tool leads to compression of the sample chamber, which is cost-efficient compared to conventional methods, such as compression molding or injection molding that require special equipment. In addition, this compact design reduces the preparation time and the heat load. The VCM tool was used to prepare samples for a rheological study of three pharmaceutical polymers (Soluplus((r)), Eudragit((r))E, EVA Rowalit((r)) 300-1/28). The prepared samples were without any air inclusions or voids, and the measurements had a high reproducibility. All relative standard deviations were below 3%. The obtained data were fitted to the Carreau-Yasuda model and time-temperature superposition was applied. PMID- 26367780 TI - Solid lipid nanoparticles (SLN) of Efavirenz as lymph targeting drug delivery system: Elucidation of mechanism of uptake using chylomicron flow blocking approach. AB - The aim of the present work was to develop a lymph targeted SLN formulation of antiretroviral (ARV) drug and to have an understanding of its underlying mechanism of uptake by the lymphatics. The lymphatics are the inaccessible reservoirs of HIV in human body. Efavirenz (EFV) is a BCS class II, ARV drug that undergoes extensive first pass metabolism. The EFV SLN formulation was prepared using Gelucire 44/14, Compritol 888 ATO, Lipoid S 75 and Poloxamer 188 by hot homogenization technique followed by ultrasonication method, with mean particle size of 168 nm, polydispersity index (PDI) <0.220, and mean zeta potential of 35.55 mV. DSC and XRPD studies revealed change in crystallinity index of drug when incorporated into SLN. In vitro drug release was found to be prolonged and biphasic in PBS pH 6.8. There was no significant change in the mean particle size, PDI, zeta potential and entrapment efficiency of EFV SLN after storage at 30 +/- 2 degrees C/60 +/- 5%RH for two months. The results from lymphatic transport and tissue distribution study indicate that a significant part of the EFV had by-passed portal system and was recovered in the lymph via chylomicron uptake mechanism. Reduction in the amount (44.70%) of the EFV reaching to liver indicates that major amount of EFV bypasses the liver and thereby, enhances the oral bioavailability of the EFV. A significant amount of EFV was found in spleen, a major lymphatic organ. EFV SLN seems to have potential to target the ARV to lymphatics for the better management of HIV. PMID- 26367781 TI - Medical examiners and Crimean-Congo hemorrhagic fever contamination risk. AB - Crimean-Congo Hemorrhagic Fever (CCHF) is an acute zoonotic infection caused by the CCHF virus. The viruses' activity peaks during April and May with a mortality rate of 3-30%. Transmission of the virus to human occurs through tick bites or exposure to infected animals' tissues or blood. The major at-risk group includes farmers living in endemic areas. Health-care workers are the second most affected group. Virus has shown up in a diverse geographic area which includes Middle East, Asia, Africa and Eastern Europe and is considered one of the most wide spread tick borne infections. The most recent cases are from Iran and Turkey. This article represents autopsy results of four CCHF infected cases in 2011 and 2012, in Ankara, Turkey. PMID- 26367782 TI - Pancytopenia As the Initial Manifestation of Brucellosis in Children. AB - Presenting with severe thrombocytopenia and pancytopenia is rare in children with brucellosis, and at the beginning it can be misdiagnosed as a hematological or a viral hemorrhagic disease. The follow-ups of 52 patients diagnosed with brucellosis from January, 2008, to December, 2013, in our clinic have shown the following results. Eleven out of these 52 patients revealed the fact that they had pancytopenia at the admission phase. Anemia and leukopenia were defined as hemoglobin levels and leukocyte counts below the standard values in terms of ages, thrombocytopenia as thrombocyte counts below 150,000/mm(3), and severe thrombocytopenia as thrombocyte counts below 20,000/mm(3). The most frequent admission symptoms and findings of the patients with pancytopenia were fever (75%), fatigue (50%), splenomegaly (75%), and hepatomegaly (41%). Laboratory results were hemoglobin 9.3+/-0.96 gram/dL, white blood cell count 2226+/ 735.9/mm(3), and thrombocyte count 70,090+/-47,961/mm(3). The standard tube agglutination test was positive for all patients, and Brucellosis spp. were isolated in the blood cultures of six (54%) patients. Three of the 11 patients had severe thrombocytopenia, and they were admitted with complaints of epistaxis, gingival bleeding, petechiae, and purpura. At the beginning, two of three cases were misdiagnosed as Crimean-Congo hemorrhagic fever (CCHF), another zoonotic endemic disease in Turkey. Pancytopenia improved with treatment of brucellosis on all patients. In conclusion, brucellosis can show great similarity with hematologic and zoonotic diseases like CCHF. Brucellosis should be considered in the differential diagnosis of pancytopenia, treatment-resistant immune thrombocytopenia, and viral hemorrhagic disease, especially in countries where brucellosis is endemic. PMID- 26367783 TI - High Frequency of Malignant Transformation of Ovarian Mature Teratoma into Squamous Cell Carcinoma in Young Patients in Northeast Brazil. AB - The malignant behavior of an ovarian teratoma is related to immaturity, or rarely to the malignant transformation of a somatic component in a mature teratoma (MT). The aim of this work was to review 189 consecutive ovarian teratomas diagnosed between 2006 and 2010 at a public referral center for cancer in Brazil, focusing on cases of MT with malignant transformation. MTs with transformation to squamous cell carcinoma (SCC) were further analyzed by immunohistochemistry for p16 staining. The median age of all patients was 36 yr (mean age, 39.6 yr; SD+/-4.9). Mature and immature teratomas represented 95.7% (181/189) and 4.2% of the cohort, respectively. Immature teratoma occurred mainly in adolescents under 18 yr. Malignant transformation of the somatic component in MT was observed in 10 of 181 patients (5.5%). SCC was the most common subtype (4/10), followed by differentiated thyroid carcinoma in struma ovarii(3/10), adenosquamous carcinoma (1/10), mucinous intestinal-type adenocarcinoma (1/10), and a well-differentiated neuroendocrine tumor/carcinoid (1/10). Two of 4 SCC cases were strong and diffusely positive for p16, and 2 were negative. In 5 further patients, MT was synchronously observed with other benign and malignant ovarian neoplasms in the ipsilateral ovary (3 mucinous cystadenomas and 1 Brenner tumor) and 1 cystadenocarcinoma in the contralateral ovary. MTs with malignant transformation were larger than those without transformation (P<0.001), but did not demonstrate any association with age. Indeed, our patients with SCC in MT were much younger [median and mean age, 37 and 38 yr (SD+/-4.9), respectively] than those described previously. As p16 is considered a surrogate marker for HPV infection, the malignant transformation of MT into SSC in young patients raises the possibility of HPV infection as a risk factor in some of these cases. However, molecular studies are needed to clarify the possible role of HPV in the malignant transformation of MT to SCC. PMID- 26367784 TI - Stromal Clues in Endometrial Carcinoma: Loss of Expression of beta-Catenin, Epithelial-Mesenchymal Transition Regulators, and Estrogen-Progesterone Receptor. AB - Epithelial-stroma interactions in the endometrium are known to be responsible for physiological functions and emergence of several pathologic lesions. Periglandular stromal cells act on endometrial cells in a paracrine manner through sex hormones. In this study, we immunohistochemically evaluated the expression of epithelial-mesenchymal transition regulators (SNAIL/SLUG, TWIST, ZEB1), adhesion molecules (beta-catenin and E-cadhenin), estrogen (ER) progesterone (PR) receptor and their correlation with each other in 30 benign, 148 hyperplastic (EH), and 101 endometrioid-type endometrial carcinoma (EC) endometria. In the epithelial component, loss of expression in E-cadherin, ER and PR, and overexpression of TWIST and ZEB1 were significantly higher in EC than in EH (P<0.01). In the periglandular stromal component, beta-catenin and SNAIL/SLUG expression were significantly higher in normal endometrium and simple without atypical EH compared with complex atypical EH and EC (P<0.01). In addition, periglandular stromal TWIST expression was significantly higher in EH group compared with EC (P<0.05). There was significantly negative correlation between beta-catenin and ER, TWIST and ER, and TWIST and PR in hyperplastic and carcinomatous glandular epithelium, whereas there was a significantly positive correlation between beta-catenin and SNAIL-SLUG, beta-catenin and TWIST, beta catenin and ER, beta-catenin and PR, SNAIL-SLUG and ER, SNAIL-SLUG and PR, TWIST and ER, TWIST and PR, in periglandular/cancer-associated stromal cells (P<0.01). In conclusion, the pattern of positive and negative correlations in the expression of epithelial-mesenchymal transition regulators (SNAIL-SLUG and TWIST), sex hormone receptors (ER and PR), and beta-catenin between ECs and hyperplasia, as well as between epithelium and stroma herein, is suggestive of a significant role for these proteins and their underlying molecular processes in the development of endometrial carcinomas. PMID- 26367785 TI - Efficacy of Hydrofiber Silver Dressing in the Treatment of Posttraumatic Skin Wounds in Children. AB - Three case reports on conservative treatment of posttraumatic open conquassant wounds in children are presented. In 2 cases, the wounds opened after rejection of a previously applied skin graft, whereas in the third case, the wound was consequential to toe amputation and treated conservatively. Based on the authors' long-standing favorable experience with this type of dressing in healing of deep burns in children, treatment was continued with the use of a hydrofiber supportive silver-containing dressing (AQUACEL Ag, ConvaTec, Bridgewater, NJ). From the beginning of treatment, wound dressing was performed on an outpatient basis and without antibiotic therapy. The wounds healed within 4-8 weeks. The process of wound healing and treatment, the mechanisms that may compromise it, and the possibilities offered by hydrofiber silver dressing in conservative treatment of posttraumatic conquassant skin wounds are discussed. PMID- 26367786 TI - The Application of Skin Adhesive to Maintain Seal in Negative Pressure Wound Therapy. AB - BACKGROUND: Optimal wound healing in negative pressure wound therapy (NPWT) depends on a properly sealed vacuum system. Anatomically difficult wounds disrupt the adhesive dressing, resulting in air leaks that impair the integrity of this system. Several techniques have been used in previous reports to prevent air leaks, including the addition of skin adhesives (eg, Skin-Prep [Smith and Nephew, St. Petersburg, FL] or compound tincture of benzoin), hydrocolloid dressings, silicone, and stoma paste. The purpose of this case report is to demonstrate the effectiveness of using a cyanoacrylate tissue adhesive, dermaFLEX (FLEXCon, Spencer, MA), in maintaining an airtight, durable seal in NPWT. MATERIALS AND METHODS: The authors present a patient with a difficult to manage anogenital wound where efforts to maintain an airtight seal in NPWT proved difficult. It was decided during the course of treatment to use the cyanoacrylate tissue adhesive to create an airtight, durable seal. The tissue adhesive was applied circumferentially to the skin surrounding the wound edge. After placement of vacuum-assisted closure foam over the wound, the adhesive dressing was applied with its edges overlapping the skin area where the tissue adhesive was applied. RESULTS: The size of the wound was visibly reduced at each dressing change. An airtight seal was consistently maintained for 3 days at a time, surviving the difficult environment of the wound and maximizing the life of each adhesive dressing. CONCLUSION: For wounds in anatomically challenging locations, the use of the tissue adhesive appears to be a safe and viable option in creating a durable seal in NPWT. PMID- 26367787 TI - Massive Localized Lymphedema in the Morbidly Obese Patient: A Clinical Entity Mimicking Lymphosarcoma. AB - Massive localized lymphedema (MLL) is a rare benign soft tissue lesion that develops in morbidly obese patients, most commonly on the medial thigh (though other locations have also been described). The cause of MLL remains unknown, but the common denominator in all reported cases is obesity. The diagnosis of MLL is usually made based on clinical history and presentation but it is believed to be underdiagnosed due to a lack of awareness of this distinct entity. When left untreated, MLL can degenerate into angiosarcoma. This report describes a case of MLL of the right lower abdominal wall in an obese 61-year-old female (BMI = 42 kg/m(2)). PMID- 26367788 TI - Epidemiology of Injuries Caused by Mammals Treated in Emergency Departments in Marseille, France. AB - A total of 304 patients with mammal-related injuries were included over the 2 year survey period (1.5% of total admissions) at the emergency departments of a large city in southern France. Admissions peaked during the summer months. Dogs accounted for 75.3% and cats for 16.8% of cases. Dog injuries were significantly more common in younger individuals. Overall, signs of infection were observed in 17.9% of cases and were more likely to occur in patients injured by cats and in patients injured more than 1 day before consulting. The majority of patients received an antibiotic prophylaxis, independent to the delay between injury and consultation. Only 1 out of 10 injured patients who consulted an emergency department were seen at the rabies treatment center. Emergency department surveillance data offers an effective and efficient method for conducting animal bite surveillance to monitor trends and characterize animal bite victims. PMID- 26367789 TI - Editorial Message:Practice Makes Perfect. PMID- 26367790 TI - The erotetic theory of delusional thinking. AB - INTRODUCTION: In this paper, we argue for a novel account of one cognitive factor implicated in delusional cognition. According to the erotetic theory of delusion we present, the central cognitive factor in delusion is impaired endogenous question raising. METHOD: After presenting the erotetic theory, we draw on it to model three distinct patterns of reasoning exhibited by delusional and schizophrenic patients, and contrast our explanations with Bayesian alternatives. RESULTS: We argue that the erotetic theory has considerable advantages over Bayesian models. Specifically, we show that it offers a superior explanation of three phenomena: the onset and persistence of the Capgras delusion; recent data indicating that schizophrenic subjects manifest superior reasoning with conditionals in certain contexts; and evidence that schizophrenic and delusional subjects have a tendency to "jump to conclusions." Moreover, since the cognitive mechanisms we appeal to are independently motivated, we avoid having to posit distinct epistemic states that are intrinsically irrational in order to fit our model to the variety of data. CONCLUSION: In contrast to Bayesian models, the erotetic theory offers a simple, unified explanation of a range of empirical data. We therefore conclude that it offers a more plausible framework for explaining delusional cognition. PMID- 26367791 TI - Operationalizing Pain Treatment in the Biopsychosocial Model: Take a Daily "SWEM" -Socialize, Work, Exercise, Meditate. AB - In the United States, chronic pain is often poorly treated at an exceedingly high cost. The use of the biomedical model to manage pain is frequently ineffective, and evidence suggests that the biopsychosocial (BPS) model is a better choice. A problem with the BPS model is that it has not been operationalized in terms of patient behavior. This commentary addresses that issue by suggesting that people with chronic pain and illness participate daily in four self-management health behaviors: socialize, work, exercise, and meditation, and discusses evidence that supports these recommendations. These self-management behaviors may decrease pain and thus reduce the need for pain medications and other medical interventions. Additional topics include patient adherence and health coaching. PMID- 26367792 TI - First complete mitochondrial genome from the brown lacewings (Neuroptera: Hemerobiidae). AB - The first complete mitochondrial genome of the family Hemerobiidae (Neuronema laminatum Tjeder, 1936) is sequenced in this study. The complete mitochondrial genome is a typical double-stranded circular molecule of 17,164 bp (GenBank accession number: KR078257) containing 37 typical animal mitochondrial gene and an A + T-rich region. The gene order is identical to that of the putative ancestral arrangement of insects and other lacewings. Thirteen protein-coding genes (PCGs) possessed common triplet initiation codons ATN and mostly terminate with TAN codons except for ND5 with a single T residue adjacent to a downstream tRNA gene. All the 22 tRNAs, ranging from 63 to 72 bp, can be folded into classic clover-leaf secondary structure except for tRNA(Ser(AGN)), in which the dihydrouridine (DHU) arm did not form a stable stem-loop structure. The control region is 2131 bp long with an A + T content of 87.4%. In the sampled families of Neuroptera, Osmylidae + the remaining families, Hemerobiidae + Mantispidae, Polystoechotidae + Rapismatidae, are recovered in phylogenetic analyses with high supports. PMID- 26367793 TI - Eyes on New Product Development. PMID- 26367795 TI - Lithospheric controls on magma composition along Earth's longest continental hotspot track. AB - Hotspots are anomalous regions of volcanism at Earth's surface that show no obvious association with tectonic plate boundaries. Classic examples include the Hawaiian-Emperor chain and the Yellowstone-Snake River Plain province. The majority are believed to form as Earth's tectonic plates move over long-lived mantle plumes: buoyant upwellings that bring hot material from Earth's deep mantle to its surface. It has long been recognized that lithospheric thickness limits the rise height of plumes and, thereby, their minimum melting pressure. It should, therefore, have a controlling influence on the geochemistry of plume related magmas, although unambiguous evidence of this has, so far, been lacking. Here we integrate observational constraints from surface geology, geochronology, plate-motion reconstructions, geochemistry and seismology to ascertain plume melting depths beneath Earth's longest continental hotspot track, a 2,000 kilometre-long track in eastern Australia that displays a record of volcanic activity between 33 and 9 million years ago, which we call the Cosgrove track. Our analyses highlight a strong correlation between lithospheric thickness and magma composition along this track, with: (1) standard basaltic compositions in regions where lithospheric thickness is less than 110 kilometres; (2) volcanic gaps in regions where lithospheric thickness exceeds 150 kilometres; and (3) low volume, leucitite-bearing volcanism in regions of intermediate lithospheric thickness. Trace-element concentrations from samples along this track support the notion that these compositional variations result from different degrees of partial melting, which is controlled by the thickness of overlying lithosphere. Our results place the first observational constraints on the sub-continental melting depth of mantle plumes and provide direct evidence that lithospheric thickness has a dominant influence on the volume and chemical composition of plume-derived magmas. PMID- 26367796 TI - BET inhibitor resistance emerges from leukaemia stem cells. AB - Bromodomain and extra terminal protein (BET) inhibitors are first-in-class targeted therapies that deliver a new therapeutic opportunity by directly targeting bromodomain proteins that bind acetylated chromatin marks. Early clinical trials have shown promise, especially in acute myeloid leukaemia, and therefore the evaluation of resistance mechanisms is crucial to optimize the clinical efficacy of these drugs. Here we use primary mouse haematopoietic stem and progenitor cells immortalized with the fusion protein MLL-AF9 to generate several single-cell clones that demonstrate resistance, in vitro and in vivo, to the prototypical BET inhibitor, I-BET. Resistance to I-BET confers cross resistance to chemically distinct BET inhibitors such as JQ1, as well as resistance to genetic knockdown of BET proteins. Resistance is not mediated through increased drug efflux or metabolism, but is shown to emerge from leukaemia stem cells both ex vivo and in vivo. Chromatin-bound BRD4 is globally reduced in resistant cells, whereas the expression of key target genes such as Myc remains unaltered, highlighting the existence of alternative mechanisms to regulate transcription. We demonstrate that resistance to BET inhibitors, in human and mouse leukaemia cells, is in part a consequence of increased Wnt/beta catenin signalling, and negative regulation of this pathway results in restoration of sensitivity to I-BET in vitro and in vivo. Together, these findings provide new insights into the biology of acute myeloid leukaemia, highlight potential therapeutic limitations of BET inhibitors, and identify strategies that may enhance the clinical utility of these unique targeted therapies. PMID- 26367794 TI - Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture. AB - The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF <= 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants, as well as rare, population-specific, coding variants. Here we identify novel non-coding genetic variants with large effects on BMD (ntotal = 53,236) and fracture (ntotal = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (n = 2,882 from UK10K (ref. 10); a population-based genome sequencing consortium), whole-exome sequencing (n = 3,549), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (n = 26,534), and de novo replication genotyping (n = 20,271). We identified a low-frequency non-coding variant near a novel locus, EN1, with an effect size fourfold larger than the mean of previously reported common variants for lumbar spine BMD (rs11692564(T), MAF = 1.6%, replication effect size = +0.20 s.d., Pmeta = 2 * 10(-14)), which was also associated with a decreased risk of fracture (odds ratio = 0.85; P = 2 * 10(-11); ncases = 98,742 and ncontrols = 409,511). Using an En1(cre/flox) mouse model, we observed that conditional loss of En1 results in low bone mass, probably as a consequence of high bone turnover. We also identified a novel low-frequency non-coding variant with large effects on BMD near WNT16 (rs148771817(T), MAF = 1.2%, replication effect size = +0.41 s.d., Pmeta = 1 * 10(-11)). In general, there was an excess of association signals arising from deleterious coding and conserved non-coding variants. These findings provide evidence that low-frequency non-coding variants have large effects on BMD and fracture, thereby providing rationale for whole-genome sequencing and improved imputation reference panels to study the genetic architecture of complex traits and disease in the general population. PMID- 26367798 TI - Transcriptional plasticity promotes primary and acquired resistance to BET inhibition. AB - Following the discovery of BRD4 as a non-oncogene addiction target in acute myeloid leukaemia (AML), bromodomain and extra terminal protein (BET) inhibitors are being explored as a promising therapeutic avenue in numerous cancers. While clinical trials have reported single-agent activity in advanced haematological malignancies, mechanisms determining the response to BET inhibition remain poorly understood. To identify factors involved in primary and acquired BET resistance in leukaemia, here we perform a chromatin-focused RNAi screen in a sensitive MLL AF9;Nras(G12D)-driven AML mouse model, and investigate dynamic transcriptional profiles in sensitive and resistant mouse and human leukaemias. Our screen shows that suppression of the PRC2 complex, contrary to effects in other contexts, promotes BET inhibitor resistance in AML. PRC2 suppression does not directly affect the regulation of Brd4-dependent transcripts, but facilitates the remodelling of regulatory pathways that restore the transcription of key targets such as Myc. Similarly, while BET inhibition triggers acute MYC repression in human leukaemias regardless of their sensitivity, resistant leukaemias are uniformly characterized by their ability to rapidly restore MYC transcription. This process involves the activation and recruitment of WNT signalling components, which compensate for the loss of BRD4 and drive resistance in various cancer models. Dynamic chromatin immunoprecipitation sequencing and self transcribing active regulatory region sequencing of enhancer profiles reveal that BET-resistant states are characterized by remodelled regulatory landscapes, involving the activation of a focal MYC enhancer that recruits WNT machinery in response to BET inhibition. Together, our results identify and validate WNT signalling as a driver and candidate biomarker of primary and acquired BET resistance in leukaemia, and implicate the rewiring of transcriptional programs as an important mechanism promoting resistance to BET inhibitors and, potentially, other chromatin-targeted therapies. PMID- 26367799 TI - Development of clinical prediction models for good or bad response to classic systemic drugs, anti-TNFs, and ustekinumab in psoriasis, based on the BIOBADADERM cohort. AB - BACKGROUND: Identifying patients likely to have very good or bad results from systemic psoriasis therapy could improve efficiency of therapy. OBJECTIVE: To develop prognostic models for good or bad response to classic systemic drugs, anti-TNFs, and ustekinumab in psoriasis. METHODS: Multivariable logistic regression of a prospective multicenter cohort of psoriatic patients in clinical practice (6449 person-years of follow-up). We used as possible predictors demographic characteristics, comorbidities, characteristics of the psoriasis (type, PASI, arthritis), history of past therapy at entry in the cohort, and history of response to previous cycles while in the cohort. We defined good response to a treatment cycle as either cycle end due to disease remission or a cycle longer than 2 years that does not end later due to inefficacy in the follow up period. Bad response to a treatment cycle was defined as a cycle that is finished due to inefficacy, based on the physician judgment, after more than 3 months of treatment. RESULTS: Patients with fewer previous therapies, lower body mass index, older at start of therapy, and with previous history of good responses to therapy are more likely to have positive results of therapy. However, the predictive characteristics of models are poor. CONCLUSION: Predictive models of clinical response to systemic drugs in psoriasis with the studied variables do not seem to outperform drug selection by a dermatologist. PMID- 26367800 TI - A role for mRNA trafficking and localized translation in peroxisome biogenesis and function? AB - Peroxisomes are distinct membrane-enclosed organelles involved in the beta oxidation of fatty acids and synthesis of ether phospholipids (e.g. plasmalogens), as well as cholesterol and its derivatives (e.g. bile acids). Peroxisomes comprise a distinct and highly segregated subset of cellular proteins, including those of the peroxisome membrane and the interior matrix, and while the mechanisms of protein import into peroxisomes have been extensively studied, they are not fully understood. Here we will examine the potential role of RNA trafficking and localized translation on protein import into peroxisomes and its role in peroxisome biogenesis and function. Given that RNAs encoding peroxisome biogenesis (PEX) and matrix proteins have been found in association with the endoplasmic reticulum and peroxisomes, it suggests that localized translation may play a significant role in the import pathways of these different peroxisomal constituents. PMID- 26367803 TI - A self-regulation-based intervention to increase physical activity in cancer patients. AB - The study examined whether a behavior-change intervention focusing on self regulatory strategies and emphasizing role model support increases physical activity (PA) among insufficiently active (not meeting PA guidelines of 150 min/week) cancer patients. Ambulatory cancer patients [N = 72; 54% female; M = 56 years, SD = 12.34; most with breast or colon cancer (34, 15%)] were enrolled in the MOTIVACTION-study, a 4-week intervention (1-hr counseling, followed by weekly phone calls), with pretest (T1), posttest (T2) and a 10-week follow-up (T3). Participants were randomized to either an exercise or to a stress management intervention (active control). The exercise intervention emphasized self regulatory strategies (e.g. action- and coping planning and self-monitoring); patients were also encouraged to contact a physically active same-sex role model as a potential exercise partner. The active control condition consisted of coping and relaxation techniques. Sixty-seven patients remained in the study and completed the SQUASH assessment of PA and a measure of perceived stress. PA was validated by Actigraph accelerometry. At T2, 46% of the patients in the exercise group and 19% of stress management patients increased their activity levels to meet PA guidelines (>150 min/week; chi(2)(1) = 5.51, p = .019). At T3, participants in the exercise intervention maintained their exercise level (46%), but also 31% of the stress management patients met the guidelines. All patients reported reductions in perceived stress. Additional analyses comparing patients in the exercise group by role model contact (63% realized contact) revealed that those who had contact with their role model were significantly more likely to adhere to the recommended guidelines (T2:50%; T3:64%) compared to those who did not have contact with a role model (T2:39%; T3:15%), suggesting the potential of mobilizing role model support to facilitate PA. In sum, cancer patients may not only benefit from an exercise intervention emphasizing self-regulation, but also from stress management, regarding both reducing stress and increasing PA. PMID- 26367802 TI - The birth of yeast peroxisomes. AB - This contribution describes the phenotypic differences of yeast peroxisome deficient mutants (pex mutants). In some cases different phenotypes were reported for yeast mutants deleted in the same PEX gene. These differences are most likely related to the marker proteins and methods used to detect peroxisomal remnants. This is especially evident for pex3 and pex19 mutants, where the localization of receptor docking proteins (Pex13, Pex14) resulted in the identification of peroxisomal membrane remnants, which do not contain other peroxisomal membrane proteins, such as the ring proteins Pex2, Pex10 and Pex12. These structures in pex3 and pex19 cells are the template for peroxisome formation upon introduction of the missing gene. Taken together, these data suggest that in all yeast pex mutants analyzed so far peroxisomes are not formed de novo but use membrane remnant structures as a template for peroxisome formation upon reintroduction of the missing gene. The relevance of this model for peroxisomal membrane protein and lipid sorting to peroxisomes is discussed. PMID- 26367801 TI - Regulation of peroxisomal matrix protein import by ubiquitination. AB - Peroxisomes are organelles that play an important role in many cellular tasks. The functionality of peroxisomes depends on the proper import of their matrix proteins. Peroxisomal matrix proteins are imported posttranslationally in a folded, sometimes even oligomeric state. They harbor a peroxisomal targeting sequence (PTS), which is recognized by dynamic PTS-receptors in the cytosol. The PTS-receptors ferry the cargo to the peroxisomal membrane, where they become part of a transient import pore and then release the cargo into the peroxisomal lumen. Subsequentially, the PTS-receptors are ubiquitinated in order to mark them for the export-machinery, which releases them back to the cytosol. Upon deubiquitination, the PTS-receptors can facilitate further rounds of cargo import. Because the ubiquitination of the receptors is an essential step in the import cycle, it also represents a central regulatory element that governs peroxisomal dynamics. In this review we want to give an introduction to the functional role played by ubiquitination during peroxisomal protein import and highlight the mechanistic concepts that have emerged based on data derived from different species since the discovery of the first ubiquitinated peroxin 15years ago. Moreover, we discuss future tasks and the potential of using advanced technologies for investigating further details of peroxisomal protein transport. PMID- 26367804 TI - Cell wall glycoproteins at interaction sites between parasitic giant dodder (Cuscuta reflexa) and its host Pelargonium zonale. AB - The process of host plant penetration by parasitic dodder (genus Cuscuta) is accompanied by molecular and structural changes at the host/parasite interface. Recently, changes in pectin methyl esterification levels in the host cell walls abutting parasitic cells in established infection sites were reported. In addition to that, we show here that the composition of cell wall glycoproteins in Cuscuta-infected Pelargonium zonale undergoes substantial changes. While several arabinogalactan protein epitopes exhibit decreased abundances in the vicinity of the Cuscuta reflexa haustorium, extensins tend to increase in the infected areas. PMID- 26367805 TI - Smoking and the Transmission of Tuberculosis. PMID- 26367797 TI - The UK10K project identifies rare variants in health and disease. AB - The contribution of rare and low-frequency variants to human traits is largely unexplored. Here we describe insights from sequencing whole genomes (low read depth, 7*) or exomes (high read depth, 80*) of nearly 10,000 individuals from population-based and disease collections. In extensively phenotyped cohorts we characterize over 24 million novel sequence variants, generate a highly accurate imputation reference panel and identify novel alleles associated with levels of triglycerides (APOB), adiponectin (ADIPOQ) and low-density lipoprotein cholesterol (LDLR and RGAG1) from single-marker and rare variant aggregation tests. We describe population structure and functional annotation of rare and low frequency variants, use the data to estimate the benefits of sequencing for association studies, and summarize lessons from disease-specific collections. Finally, we make available an extensive resource, including individual-level genetic and phenotypic data and web-based tools to facilitate the exploration of association results. PMID- 26367806 TI - Reply: To PMID 25105895. PMID- 26367807 TI - Testing International Adoptees for Tuberculosis. PMID- 26367808 TI - An Adult Ascaris Worm Entrapped in a Pulmonary Tuberculous Cavity. PMID- 26367809 TI - Usefulness of Interferon-gamma Release Assays in the Screening of Latent Tuberculosis Infection in Immigrant and Internationally Adopted Children. PMID- 26367810 TI - An Invasive Pneumococcal Infection Due to Streptococcus pneumoniae Serotype 24. PMID- 26367811 TI - Vaccine Failure After Meningococcal C Conjugate Vaccine May Be Linked to Decline of Bactericidal Titers and Absence of Herd Immunity. PMID- 26367812 TI - Salmonella enterica subsp. arizonae Meningitis in a Neonate Exposed to a Corn Snake. PMID- 26367813 TI - Virulence profile: Michail Lionakis. PMID- 26367814 TI - Outcome of the first Medicines Utilization Research in Africa group meeting to promote sustainable and rational medicine use in Africa. AB - The first Medicines Utilization Research in Africa group workshop and symposium brought researchers together from across Africa to improve their knowledge on drug utilization methodologies as well as exchange ideas. As a result, progress was made on drug utilization research and formulating future strategies to enhance the rational use of medicines in Africa. Anti-infectives were the principal theme for the 1-day symposium following the workshops. This included presentations on the inappropriate use of antibiotics as well as ways to address this. Concerns with adverse drug reactions and adherence to anti-retroviral medicines were also discussed, with poor adherence remaining a challenge. There were also concerns with the underutilization of generics. These discussions resulted in a number of agreed activities before the next conference in 2016. PMID- 26367815 TI - Endoscopic endonasal dacryocystorhinostomy with ostial stent intubation following nasolacrimal duct stent incarceration. PMID- 26367816 TI - Easy conversion of protein-rich enoki mushroom biomass to a nitrogen-doped carbon nanomaterial as a promising metal-free catalyst for oxygen reduction reaction. AB - The search for low-cost, highly active, and stable catalysts to replace the Pt based catalysts for oxygen reduction reaction (ORR) has recently become a topic of interest. Herein, we report a new strategy to design a nitrogen-doped carbon nanomaterial for use as a metal-free ORR catalyst based on facile pyrolysis of protein-rich enoki mushroom (Flammulina velutipes) biomass at 900 degrees C with carbon nanotubes as a conductive agent and inserting matrix. We found that various forms of nitrogen (nitrile, pyrrolic and graphitic) were incorporated into the carbon molecular skeleton of the product, which exhibited more excellent ORR electrocatalytic activity and better durability in alkaline medium than those in acidic medium. Remarkably, the ORR half-wave potential measured on our material was around 0.81 V in alkaline medium, slightly lower than that on the commercial 20 wt% Pt/C catalyst (0.86 V). Meanwhile, the ORR followed the desired 4-electron transfer mechanism involving the direct reduction pathway. The ORR performance was also markedly better than or at least comparable to the leading results in the literature based on biomass-derived carbon-based catalysts. Besides, we significantly proposed that the graphitic-nitrogen species that is most responsible for the ORR activity can function as the electrocatalytically active center for ORR, and the pyrrolic-nitrogen species can act as an effective promoter for ORR only. The results suggested a promising route based on economical and sustainable fungi biomass towards the large-scale production of valuable carbon nanomaterials as highly active and stable metal-free catalysts for ORR under alkaline conditions. PMID- 26367817 TI - Evidence from pupillometry and fMRI indicates reduced neural response during vicarious social pain but not physical pain in autism. AB - Autism spectrum disorder (ASD) is characterized by substantial social deficits. The notion that dysfunctions in neural circuits involved in sharing another's affect explain these deficits is appealing, but has received only modest experimental support. Here we evaluated a complex paradigm on the vicarious social pain of embarrassment to probe social deficits in ASD as to whether it is more potent than paradigms currently in use. To do so we acquired pupillometry and fMRI in young adults with ASD and matched healthy controls. During a simple vicarious physical pain task no differences emerged between groups in behavior, pupillometry, and neural activation of the anterior insula (AIC) and anterior cingulate cortex (ACC). In contrast, processing complex vicarious social pain yielded reduced responses in ASD on all physiological measures of sharing another's affect. The reduced activity within the AIC was thereby explained by the severity of autistic symptoms in the social and affective domain. Additionally, behavioral responses lacked correspondence with the anterior cingulate and anterior insula cortex activity found in controls. Instead, behavioral responses in ASD were associated with hippocampal activity. The observed dissociation echoes the clinical observations that deficits in ASD are most pronounced in complex social situations and simple tasks may not probe the dysfunctions in neural pathways involved in sharing affect. Our results are highly relevant because individuals with ASD may have preserved abilities to share another's physical pain but still have problems with the vicarious representation of more complex emotions that matter in life. PMID- 26367818 TI - Synthesis of the A-D Ring System of the Gambieric Acids. AB - The A-D fragment of gambieric acids A and C has been synthesized using an asymmetric Tsuji-Trost allylation reaction to couple the two key segments. The A ring fragment has been prepared by a short and highly efficient route involving diastereoselective Lewis acid mediated alkylation of an acetal. Iterative ring closing metathesis reactions have been used to construct cyclic ethers and assemble the tricyclic B-D fragment. PMID- 26367819 TI - Design of D flip-flop and T flip-flop using Mach-Zehnder interferometers for high speed communication. AB - Electrical component speed is a major constraint in high-speed communications. To overcome this constraint, electrical components are now being replaced by optical components. The application of optical switching phenomena has been used to construct the design of the D flip-flop and T flip-flop based on the electro optic effect in a Mach-Zehnder interferometer (MZI). The MZI structures show the powerful ability to switch the optical signal from one output port to the other. Hence, it is possible to construct some complex optical combinational digital circuits using the electro-optic-effect-based MZI structure as a basic building block. This paper constitutes the mathematical description of the proposed device and thereafter compilation using MATLAB. The study is carried out by simulating the proposed device with the beam propagation method. PMID- 26367820 TI - Novel time-of-flight fiber dispersion measurement technique using supercontinuum light sources and acousto-optical tunable filters. AB - Long-distance fiber links require precise knowledge of fiber dispersion characteristics. Similar dispersion characteristics are necessary for supercontinuum broadband laser absorption spectroscopy (SCLAS) to allow proper data evaluation and species concentration determination, as well as numerous other applications. In this work, a time-of-flight approach to measuring the dispersion characteristic of fibers with supercontinuum laser light sources (SCLs) and acousto-optical tunable filters (AOTFs) is presented. Broadband emission of the SCL is filtered with a narrowband AOTF and dispersed in time by the fiber under test. By using the wavelength-specific delay, the dispersion characteristic can be calculated. The technique is especially suited for longer fibers and was verified against a state-of-the-art phase-shift-based dispersion measurement system. Advantages of the new approach include solely utilizing SCLAS system components, as well as a high level of automation and wide spectral coverage, ranging from 1100 to 1700 nm in a single measurement setup. PMID- 26367822 TI - Creating optical filters with angular-selective light transmission. AB - A simple method for designing and calculating grating optical filters with angular-selective light transmission is presented. The selectivity is provided by the relative positions of two surface gratings formed by directionally transmissive strips, alternating with absorptive, reflective, or scattering strips. As the incidence angle changes, the proportion of radiation that passes through both gratings also changes. Geometric and optical filter parameters are calculated to achieve a light transmittance with a predetermined angular dependence. This method can be used to create neutral-density, frequency, and spatial filters pre-adapted to incidence angles that change when the light source moves relative to the filter. PMID- 26367821 TI - Numerical wave propagation in ImageJ. AB - An ImageJ plugin for numerical wave propagation is presented. The plugin provides ImageJ, the well-known software for image processing, with the capability of computing numerical wave propagation by the use of angular spectrum, Fresnel, and Fresnel-Bluestein algorithms. The plugin enables numerical wave propagation within the robust environment provided by the complete set of built-in tools for image processing available in ImageJ. The plugin can be used for teaching and research purposes. We illustrate its use to numerically recreate Poisson's spot and Babinet's principle, and in the numerical reconstruction of digitally recorded holograms from millimeter-sized and pure phase microscopic objects. PMID- 26367823 TI - Gate-controlled diode structure based electro-optical interfaces in standard silicon-CMOS integrated circuitry. AB - In this paper, we discuss the emission of visible light by a monolithically integrated silicon gate-controlled diode with the p-n junction reverse-biased. Since the MOS-like diode utilizes the field effect to modulate the optical output, the modulation speed will benefit from this mechanism. Hence, a silicon gate-controlled diode structure for optical modulation analyzed its modulation principle, its dynamic characteristics are presented, and the bandwidth of the device is considered to approach GHz in theory due to the field-induced emission mechanism. The prototype MOS-like diode opens up the design of multiterminal silicon light emitting devices (LEDs), where gate electrodes with more than one gate contact overlap several junctions with different junction intersection geometries. The device appears as a good candidate for optical modulation within silicon technology. PMID- 26367824 TI - On-orbit calibration approach for star cameras based on the iteration method with variable weights. AB - To perform efficient on-orbit calibration for star cameras, we developed an attitude-independent calibration approach for global optimization and noise removal by least-square estimation using multiple star images, with which the optimal principal point, focal length, and the high-order focal plane distortion can be obtained in one step in full consideration of the interaction among star camera parameters. To avoid the problem when stars could be misidentified in star images, an iteration method with variable weights is introduced to eliminate the influence of misidentified star pairs. The approach can increase the precision of least-square estimation and use fewer star images. The proposed approach has been well verified to be precise and robust in three experiments. PMID- 26367825 TI - Controlling mid-spatial frequency errors in magnetorheological jet polishing with a simple vertical model. AB - Mid-spatial frequency (MSF) errors are always produced in magnetorheological jet polishing (MJP) with a simple vertical jetting model and require a control during the process. The relation between a surface with MSF errors and power spectral density is analyzed. Based on this, various concepts and methods are developed to restrain the MSF errors in MJP. With a cut-off frequency, the appropriate removal function is adopted. In addition, a dedicated path with uniform characteristics is designed for polishing. The weighted iterative algorithm is proposed to get a continuous and effective dwell time map. The duplication ratio is utilized to increase the nonuniformity of the surface. The experiments are deployed in a MJP run. The peak-to-valley and root mean square of the surface are reduced from 0.384lambda and 0.077lambda (lambda=632.8 nm), respectively to 0.054lambda and 0.007lambda, respectively, and the smooth PSD curves are produced with low and smooth distribution. PMID- 26367826 TI - Heat-stop structure design with high cooling efficiency for large ground-based solar telescope. AB - A heat-stop is one of the most important thermal control devices for a large ground-based solar telescope. For controlling the internal seeing effect, the temperature difference between the heat-stop and the ambient environment needs to be reduced, and a heat-stop with high cooling efficiency is required. In this paper, a novel design concept for the heat-stop, in which a multichannel loop cooling system is utilized to obtain higher cooling efficiency, is proposed. To validate the design, we analyze and compare the cooling efficiency for the multichannel and existing single-channel loop cooling system under the same conditions. Comparative results show that the new design obviously enhances the cooling efficiency of the heat-stop, and the novel design based on the multichannel loop cooling system is obviously better than the existing design by increasing the thermal transfer coefficient. PMID- 26367828 TI - Demonstration of extended capture range for James Webb Space Telescope phase retrieval. AB - A geometrical phase retrieval (GPR) algorithm is applied to the problem of image stacking in order to extend the capture range of normal phase retrieval (PR) on the James Webb Space Telescope (JWST), and potentially eliminate a lengthy image stacking process that is based on centroids. Computer simulations are used to establish the capture range of the existing PR algorithm for JWST and demonstrate that it is increased by more than a factor of 10 when combined with GPR, guaranteeing PR capture 95% of the time. An experiment using a scale optical model of JWST was conducted to demonstrate the effectiveness of the GPR algorithm in both coherent and incoherent imaging. PMID- 26367827 TI - In vivo tissue injury mapping using optical coherence tomography based methods. AB - An injury causes changes in the optical attenuation coefficient (OAC) of a light beam traveling inside a tissue. We report a method called tissue injury mapping (TIM), which utilizes a noninvasive in vivo optical coherence tomography approach to generate an OAC and microvascular map of the injured tissue. Using TIM, the infarct region development in a mouse cerebral cortex during a stroke is visualized. Moreover, we demonstrate the changes in human facial skin structure and microvasculature during an acne lesion development from initiation to scarring. The results indicate that TIM may be used to aid in the characterization and the treatment of various diseases by enabling a high resolution detection of tissue structural and microvascular changes. PMID- 26367829 TI - Direct detection of aggregates in highly turbid colloidal suspensions of polystyrene nanoparticles. AB - We demonstrate a total internal reflection-based method that detects, for the first time to the best of our knowledge, directly without any sample dilution or special sample preparation, the presence of aggregates in highly turbid aqueous suspensions of polystyrene nanospheres. Aggregation is induced by changing either the sample pH or ionic strength. The polystyrene mass density in our samples is two orders of magnitude higher than previously reported polystyrene aggregation studies. In cases when aggregates have formed but do not yet occupy a significant fraction of the sample volume, our sensor outperforms state of the art techniques such as dynamic light scattering in terms of sensitivity. Conversely, when the sample volume is dominated by aggregates, our sensor is not as effective. PMID- 26367830 TI - Extension of light transmission distance of single-mode fiber using a microaxicon lensed fiber end. AB - The light signal through single-mode fiber is unstable, rapidly decays as it propagates, and has limited effective transmission distance. In this study, to extend its transmission distance, a microaxicon was designed at the single-mode fiber end and the emitted light analyzed via simulations and experiments. Results indicate that an 80 MUm maximum transmission distance is achievable with the microaxicon at a 45 degrees base angle. Further, the divergence angle of the light is reduced from 4.1 degrees to 0.47 degrees , its stability is improved by 97%, and the light spot is sharp at 70-80 MUm away from the fiber end. PMID- 26367831 TI - Compound dichroic polarizers with wavelength-dependent transmission axes. AB - Compound dichroic polarizers using liquid crystal polymers and dichroic dyes have been studied for their variation of polarization with wavelength. Compound dichroic polarizers are composed of multilayer polarizers, where each layer has a different orientation and absorption spectrum. Several wavelength-dependent transmission axes configurations are proposed and investigated. Polarization properties, such as linear and circular diattenuation of the compound dichroic polarizers, for different wavelengths are measured and compared with simulation. Depending on the configuration, the compound dichroic polarizers can convert polarization signatures into color coding in unique ways. PMID- 26367832 TI - Imaging local acoustic pressure in microchannels. AB - A method for determining the spatially resolved acoustic field inside a water filled microchannel is presented. The acoustic field, both amplitude and phase, is determined by measuring the change of the index of refraction of the water due to local pressure using stroboscopic illumination. Pressure distributions are measured for the fundamental pressure resonance in the water and two higher harmonic modes. By combining measurement at a range of excitation frequencies, a frequency map of modes is made, from which the spectral line width and Q-factor of individual resonances can be obtained. PMID- 26367833 TI - Synthesis of statistical properties of a randomly fluctuating polarized field. AB - An experimental technique for the synthesis of statistical properties of a randomly fluctuating polarized field is investigated and experimentally demonstrated. The technique offers the controlled synthesis of coherence and polarization and subsequent analysis of the synthesized field is carried out by making use of two-point intensity correlation and the speckle holographic technique. The controlled synthesis is achieved by using an aperture of specific size at the source plane and generating a vortex in one of the orthogonal polarization components of the polarized field, thereby producing a singularity in off-diagonal elements of the coherence-polarization matrix. PMID- 26367834 TI - Metal crack propagation monitoring by photoluminescence enhancement of quantum dots. AB - A visualization method for monitoring minor metal crack propagation is presented in this paper. Through CdS@ZnS core-shell quantum dots (QDs) enhanced emission of photoluminescence (PL), this crack detection method provides a visualization signal in real time and through a noncontact fashion. The crack of the CdS@ZnS core-shell QDs-epoxy resin kept a synchronous propagation with the metal crack. Detection of the tip growth in the film layers demonstrated that the actual crack propagation on the metal surface could be deduced from the tips in the film layers. The fluorescence peak tended to increase along the crack from the initial opening to the tip. Crack width as small as 10 MUm can be detected with a precision of 0.1 MUm and the minimum crack tip width of the QDs-epoxy resin was measured as 0.72 MUm. PMID- 26367835 TI - Improving the performance of gold nanohole array biosensors by controlling the optical collimation conditions. AB - An experimental investigation on how the bulk and surface sensitivities of gold nanohole arrays fabricated by interference lithography affect the degree of white light beam collimation is presented. The optical transmission response of nanohole arrays has been recorded by focused and collimated beam transmission spectra. The results show that both the bulk and surface sensitivities for the collimated case are much larger than for the focused case. In particular, the shape of the spectra was dependent on the degree of beam collimation. The results showed that improved sensing performance (around 3.5 times) and higher figure of merit (around 4.4 times) can be obtained by simply adjusting the incident/collection experimental conditions in transmission measurements. PMID- 26367836 TI - Simultaneous digital super-resolution and nonuniformity correction for infrared imaging systems. AB - In this article, we present a novel algorithm to achieve simultaneous digital super-resolution and nonuniformity correction from a sequence of infrared images. We propose to use spatial regularization terms that exploit nonlocal means and the absence of spatial correlation between the scene and the nonuniformity noise sources. We derive an iterative optimization algorithm based on a gradient descent minimization strategy. Results from infrared image sequences corrupted with simulated and real fixed-pattern noise show a competitive performance compared with state-of-the-art methods. A qualitative analysis on the experimental results obtained with images from a variety of infrared cameras indicates that the proposed method provides super-resolution images with significantly less fixed-pattern noise. PMID- 26367837 TI - Fabrication, measurement, and application of 20/400 Yb-doped fiber. AB - We demonstrate an excellent 20/400 Yb-doped fiber in this work, from fabrication and measurement to application. To obtain good laser properties, some crucial parameters including the refractive index profile, geometrical morphology, and coating require precise controlling. Through a 7:1 pump combiner with six 120 W 915 nm fiber-coupled pump diode modules, a single all-fiber laser oscillator generated 500 W of continuous wave signal power at 1080 nm with 76.4% slope efficiency that is close to the theoretical limit. The signal power showed no evidence of roll-over and the highest output power was limited only by available pump power. This excellent 20/400 Yb-doped fiber could find application in higher power fiber lasers. PMID- 26367838 TI - Precise design of two-dimensional diffractive optical elements for beam shaping. AB - Diffractive optical elements (DOEs) for beam shaping are widely used in many fields, and there are many kinds of optimization algorithms to design the DOEs for beam shaping. However, only the intensity distribution of the selected sampling points is controlled by these optimization algorithms. The intensity distribution of other points on the output plane is always far away from the ideal distribution. The reason is that the sampling interval on the output plane is not small enough. In this paper, a new modified GS algorithm is presented with a small enough sampling interval on the output plane. A two-dimensional DOE for beam shaping is designed, and the simulation results and the experimental results demonstrate the good performance of this algorithm. PMID- 26367839 TI - Assessment of minimum permissible geometrical parameters of a near-to-eye display. AB - Light weight and small dimensions are some of the most important characteristics of near-to-eye displays (NEDs). These displays consist of two basic parts: a microdisplay for generating an image and supplementary optics in order to see the image. Nowadays, the pixel size of microdisplays may be less than 4 MUm, which makes the supplementary optics the major factor in defining restrictions on a NED dimensions or at least on the distance between the microdisplay and the eye. The goal of the present work is to find answers to the following two questions: how small this distance can be in principle and what is the microdisplay maximum resolution that stays effective to see through the supplementary optics placed in immediate vicinity of the eye. To explore the first question, we consider an aberration-free magnifier, which is the initial stage in elaboration of a real optical system. In this case, the paraxial approximation and the transfer matrix method are ideal tools for simulation of light propagation from the microdisplay through the magnifier and the human eye's optical system to the retina. The human eye is considered according to the Gullstrand model. Parameters of the magnifier, its location with respect to the eye and the microdisplay, and the depth of field, which can be interpreted as the tolerance of the microdisplay position, are determined and discussed. The second question related to the microdisplay maximum resolution is investigated by using the principles of wave optics. PMID- 26367840 TI - Mathematical model for hybrid and panoramic stereovision systems: panoramic to rectilinear conversion model. AB - This paper introduces a new generic model for a stereovision system composed of a perspective camera and a panoramic camera or of two panoramic cameras. We present a new simple model in order to establish matching images and to formulate 3D reconstruction. Indeed, we show that composed cubic splines functions are suitable for conventional and wide-angle cameras and accurately model tangential and radial distortions. Matching is greatly simplified using this technique, and classical methods can be used to evaluate the relationship between image pairs and to achieve 3D reconstruction. Such a technique allows us to model complex forms of distortions, as in the case for panomorph lenses. PMID- 26367841 TI - Error analysis of aspheric surface with reference datum. AB - Severe requirements of location tolerance provide new challenges for optical component measurement, evaluation, and manufacture. Form error, location error, and the relationship between form error and location error need to be analyzed together during error analysis of aspheric surface with reference datum. Based on the least-squares optimization method, we develop a least-squares local optimization method to evaluate form error of aspheric surface with reference datum, and then calculate the location error. According to the error analysis of a machined aspheric surface, the relationship between form error and location error is revealed, and the influence on the machining process is stated. In different radius and aperture of aspheric surface, the change laws are simulated by superimposing normally distributed random noise on an ideal surface. It establishes linkages between machining and error analysis, and provides an effective guideline for error correcting. PMID- 26367842 TI - Perceptual quality measurement of 3D images based on binocular vision. AB - Three-dimensional (3D) technology has become immensely popular in recent years and widely adopted in various applications. Hence, perceptual quality measurement of symmetrically and asymmetrically distorted 3D images has become an important, fundamental, and challenging issue in 3D imaging research. In this paper, we propose a binocular-vision-based 3D image-quality measurement (IQM) metric. Consideration of the 3D perceptual properties of the primary visual cortex (V1) and the higher visual areas (V2) for 3D-IQM is the major technical contribution to this research. To be more specific, first, the metric simulates the receptive fields of complex cells (V1) using binocular energy response and binocular rivalry response and the higher visual areas (V2) using local binary patterns features. Then, three similarity scores of 3D perceptual properties between the reference and distorted 3D images are measured. Finally, by using support vector regression, three similarity scores are integrated into an overall 3D quality score. Experimental results for two public benchmark databases demonstrate that, in comparison with most current 2D and 3D metrics, the proposed metric achieves significantly higher consistency in alignment with subjective fidelity ratings. PMID- 26367843 TI - Comparison of bandwidth and sensitivity of long-period gratings in single-mode and few-mode fibers. AB - We present a comparative study of the bandwidth and the sensitivity of the resonance wavelength of long-period gratings (LPGs) to external perturbation fabricated in single-mode fibers (SMFs) and few-mode fibers (FMFs), and their dependencies on the group indices and the dispersion properties of the phase matched modes. Unlike SMFs, a relatively large core size of FMFs invariably leads to nonuniform index modulation across the fiber cross section under UV exposure, enabling the coupling between modes having dissimilar azimuthal symmetry. Simple analytical formulas for the group/effective index difference, dispersion difference, bandwidth, and wavelength sensitivities are derived for the case of SMFs where light is coupled from the fundamental core mode to the symmetrical cladding modes. Our results show that a two-mode fiber operating at a V-number close to 3 is capable of producing LPGs with broader bandwidth and higher sensitivity as compared with their SMF counterparts, except for a few special cases. Our analyses provide insights into the characteristics of LPGs and facilitate their designs for specific applications. PMID- 26367844 TI - Thermal and optical design analyses, optimizations, and experimental verification for a novel glare-free LED lamp for household applications. AB - Light-emitting diode (LED) technologies are undergoing very fast developments to enable household lamp products with improved energy efficiency and lighting properties at lower cost. Although many LED replacement lamps are claimed to provide similar or better lighting quality at lower electrical wattage compared with general-purpose incumbent lamps, certain lighting characteristics important to human vision are neglected in this comparison, which include glare-free illumination and omnidirectional or sufficiently broad light distribution with adequate homogeneity. In this paper, we comprehensively investigate the thermal and lighting performance and trade-offs for several commercial LED replacement lamps for the most popular Edison incandescent bulb. We present simulations and analyses for thermal and optical performance trade-offs for various LED lamps at the chip and module granularity levels. In addition, we present a novel, glare free, and production-friendly LED lamp design optimized to produce very desirable light distribution properties as demonstrated by our simulation results, some of which are verified by experiments. PMID- 26367845 TI - Zernike-like systems in polygons and polygonal facets. AB - Zernike polynomials are commonly used to represent the wavefront phase on circular optical apertures, since they form a complete and orthonormal basis on the unit disk. In [Opt. Lett.32, 74 (2007)10.1364/OL.32.000074OPLEDP0146-9592] we introduced a new Zernike basis for elliptic and annular optical apertures based on an appropriate diffeomorphism between the unit disk and the ellipse and the annulus. Here, we present a generalization of this Zernike basis for a variety of important optical apertures, paying special attention to polygons and the polygonal facets present in segmented mirror telescopes. On the contrary to ad hoc solutions, most of them based on the Gram-Smith orthonormalization method, here we consider a piecewise diffeomorphism that transforms the unit disk into the polygon under consideration. We use this mapping to define a Zernike-like orthonormal system over the polygon. We also consider ensembles of polygonal facets that are essential in the design of segmented mirror telescopes. This generalization, based on in-plane warping of the basis functions, provides a unique solution, and what is more important, it guarantees a reasonable level of invariance of the mathematical properties and the physical meaning of the initial basis functions. Both the general form and the explicit expressions for a typical example of telescope optical aperture are provided. PMID- 26367846 TI - Transmitting characteristics of polarization information under seawater. AB - We have presented the performance evaluation for light communication under water based on polarization information. In particular, we focused on the transmitting characteristics of the polarized lights under different conditions of water types and link distances. The trajectories of transmitted photons propagating in a water channel can be simulated based on the Monte Carlo (MC) algorithm. The simulated results demonstrate that the intensity of the polarized light after being transmitted underwater decreases sharply as the transmission distance increases, but the degree of polarization (DoP) of the transmitted lights remains above 0.75. The polarization retrieve (PR) method is used for reducing the scattering impact on the DoP of the light, and the maximal enhancement of the linear degree of polarization (LDoP) can be obtained as about 16%. Meanwhile, the modified PR method with a different retrieval Mueller matrix (RMM) derived from different distances (l) of the transmission channel has also been investigated, which shows that the retrieval accuracy will be enhanced with the increase of transmission distance of the RMM. PMID- 26367847 TI - Photometry-based estimation of the total number of stars in the Universe. AB - A novel photometry-based estimation of the total number of stars in the Universe is presented. The estimation method is based on the energy conservation law and actual measurements of the extragalactic background light levels. By assuming that every radiated photon is kept within the Universe volume, i.e., by approximating the Universe as an integrating cavity without losses, the total number of stars in the Universe of about 6*1022 has been obtained. PMID- 26367848 TI - Z-scan measurement of nonlinear optical properties of BiOCl nanosheets. AB - Bismuth oxyhalides, such as bismuth oxychlorides (BiOCl), are layered materials with [Bi2O2]2+ layers sandwiched between two sheets of Cl ions. Much work has focused on the potential for bismuth oxyhalides to be a photocatalyst, but their nonlinear optical properties are rarely studied. In this work, the nonlinear refractive index of BiOCl nanosheets has been characterized with Z-scan measurement under 800 nm femtosecond pulsed laser excitation. A shift from saturable absorption to reverse saturable absorption was observed at higher input pump intensities in the experiments. The transition process was analyzed using a phenomenological model based on saturable absorption and two-photon absorption. PMID- 26367849 TI - Nonresonant and resonant cloaking of an electrically large dielectric spherical object by a multilayer isotropic metamaterial cover. AB - Mie theory and genetic algorithms are used to determine the parameters and performance of cloaks made of homogeneous isotropic metamaterials that would hide a spherical dielectric object of size comparable to the incident radiation wavelength. A single-layer (SL) cover with negative permittivity and permeability can produce a much greater reduction in the extinction efficiency than one with the permittivity and permeability of positive or opposite signs. Minimization of the extinction efficiency in the former case leads to both nonresonant and resonant solutions. Adding a second layer to the cover can lead to a significant enhancement of the bandwidth, but only to a modest reduction in the extinction efficiency at the design wavelength. In the SL case, Debye's scattering series is used to show that the nonresonant and resonant minima of the extinction efficiency correspond to scattering phase shifts approximately equal to zero and pi, respectively, and to understand the simple approximate expressions for the cloak parameters of the nonresonant solutions. The series also explains the value of the outer radius of a multilayer cloak, provides a link to a previously studied isotropic approximation to a transformation optics cloak, and indicates that a cloak consisting of an odd number of alternate double-negative and double positive layers will probably give the best possible performance. PMID- 26367850 TI - Low Yield of Myocardial Perfusion Imaging in Asymptomatic Patients With Atrial Fibrillation. PMID- 26367852 TI - Thermally Activated Delayed Fluorescence Materials Based on Homoconjugation Effect of Donor-Acceptor Triptycenes. AB - Donor-acceptor triptycences, TPA-QNX(CN)2 and TPA-PRZ(CN)2, were synthesized and their emissive properties were studied. They exhibited a blue-green fluorescence with emission lifetimes on the order of a microsecond in cyclohexane at room temperature. The long lifetime emission is quenched by O2 and is attributed to thermally activated delayed florescence (TADF). Unimolecular TADF is made possible by the separation and weak coupling due to homoconjugation of the HOMO and LUMO on different arms of the three-dimensional donor-acceptor triptycene. Organic light emitting devices (OLEDs) were fabricated using TPA-QNX(CN)2 and TPA PRZ(CN)2 as emitters which displayed electroluminescence with efficiencies as high as 9.4% EQE. PMID- 26367853 TI - Subject-Specific Carpal Ligament Elongation in Extreme Positions, Grip, and the Dart Thrower's Motion. AB - This study examined whether the radiocarpal and dorsal capsular ligaments limit end-range wrist motion or remain strained during midrange wrist motion. Fibers of these ligaments were modeled in the wrists of 12 subjects over multiple wrist positions that reflect high demand tasks and the dart thrower's motion. We found that many of the volar and dorsal ligaments were within 5% of their maximum length throughout the range of wrist motion. Our finding of wrist ligament recruitment during midrange and end-range wrist motion helps to explain the complex but remarkably similar intersubject patterns of carpal motion. PMID- 26367854 TI - Quantitative Targeted Absolute Proteomics for 28 Transporters in Brush-Border and Basolateral Membrane Fractions of Rat Kidney. AB - The purpose of the present study was to determine the absolute protein expression levels of various transporters in renal brush-border membrane (BBM) and basolateral membrane (BLM) fractions, in order to understand the quantitative differences in average transport activities among different transporters at each cellular membrane. BBM and BLM fractions of rat kidney were prepared and digested with trypsin, and simultaneous absolute quantification of 28 transporters and a BLM marker, Na(+)/K(+)-ATPase, was performed using our established quantitative targeted absolute proteomics (QTAP) technique. In BBM fraction, the protein expression levels of bcrp, urat1, mate1, octl1, mrp4, mdr1a, and abca3 were 40.3, 22.2, 8.90, 4.85, 4.69, 3.22, and 0.976 fmol/MUg protein, respectively. In BLM fraction, the protein expression levels of oat1, oat3, oct1, mrp6, and mrp1 were 10.6, 10.2, 4.59, 0.724, and 0.271 fmol/MUg protein, respectively. The expression levels of abca2, abca4, abca5, abca12, abcb4, mrp5, abcc9, abcg1, abcg5, lat1, ntcp, pgt, oatp2b1, oatp1b2, oatp3a1, and oct3 were under the limit of quantification in both fractions. The quantitative transporter protein expression profiles at these membranes, as determined by QTAP analysis, should be helpful to understand the contributions of individual transporters to renal excretion of xenobiotics and endogenous compounds. PMID- 26367855 TI - Numerical modeling of solid-phase microextraction: binding matrix effect on equilibrium time. AB - Solid-phase microextraction (SPME) is a well-known sampling and sample preparation technique used for a wide variety of analytical applications. As there are various complex processes taking place at the time of extraction that influence the parameters of optimum extraction, a mathematical model and computational simulation describing the SPME process is required for experimentalists to understand and implement the technique without performing multiple costly and time-consuming experiments in the laboratory. In this study, a mechanistic mathematical model for the processes occurring in SPME extraction of analyte(s) from an aqueous sample medium is presented. The proposed mechanistic model was validated with previously reported experimental data from three different sources. Several key factors that affect the extraction kinetics, such as sample agitation, fiber coating thickness, and presence of a binding matrix component, are discussed. More interestingly, for the first time, shorter or longer equilibrium times in the presence of a binding matrix component were explained with the help of an asymptotic analysis. Parameters that contribute to the variation of the equilibrium times are discussed, with the assumption that one binding matrix component is present in a static sample. Numerical simulation results show that the proposed model captures the phenomena occurring in SPME, leading to a clearer understanding of this process. Therefore, the currently presented model can be used to identify optimum experimental parameters without the need to perform a large number of experiments in the laboratory. PMID- 26367856 TI - Investigating Implausible Gestational Age and High Birthweight Combinations. AB - BACKGROUND: Birth certificate data overestimate national preterm births because a high percentage of last menstrual period (LMP) dates have errors. Study goals were to determine: (i) To what extent errors in transfer of birthweight and LMP date from medical records to birth certificates contribute to implausibly high birthweight-for-gestational-age births; (ii) What percentage of implausible births would be resolved if the clinical estimate (CE) from birth certificates were used instead of LMP-based gestational age, and with what degree of certainty; and (iii) Of those not resolved, what percentage had a medical explanation. METHODS: Medical records and birth certificates for all singleton infants with implausibly high birthweight-for-gestational-age based on LMP delivered in the Kaiser Permanente Northwest system in Oregon during 1998-2007 were examined. Percentages of implausible records resolved under various scenarios were calculated. RESULTS: A total of 100 births with implausibly high birthweight-for-gestational age combinations were identified. When LMP date and birthweight from medical records were used instead of from birth certificates, 31% of births with implausible combinations were resolved. Substituting the CE on the birth certificate for the LMP date resolved 92%. Of the latter, the clinician's gestational age estimate in the medical record was obtained in early pregnancy in 72%. Five of the eight births with unresolved implausible combinations were to mothers with diabetes; the remaining three had no documented medical explanation. CONCLUSIONS: In this study, use of the birth certificate CE rather than the LMP resulted in a clinically reliable reclassification for the majority of implausible birthweight-for-gestational age deliveries. PMID- 26367857 TI - Use of the chimeric anterolateral thigh free flap in lower extremity reconstruction. AB - BACKGROUND: Reconstruction of three-dimensional lower extremity defects is challenging because the dead space should be filled and the surface defect should be covered to prevent complications. We present our experience using the vastus lateralis muscle-chimeric anterolateral thigh (ALT) free flap for reconstructing three-dimensional lower extremity defects. METHODS: This report describes 12 cases of three-dimensional lower extremity defects that were treated via reconstruction using a chimeric ALT free flap between October 2010 and January 2015. The defects involved the foot (10 patients), distal lower leg (1 patient), and proximal lower leg (1 patient). The sizes of the surface defects ranged from 7.5 * 3 cm(2) to 16 * 7 cm(2), and the sizes of the estimated dead spaces ranged from 2 * 3 cm(2) to 8 * 5 cm(2). The skin and muscle segment sizes were also evaluated. RESULTS: The sizes of the skin flaps ranged from 8 * 4 cm(2) to 17.5 * 8 cm(2), and the sizes of the muscle segments ranged from 2 * 3 cm(2) to 9 * 5 cm(2). Eleven cases exhibited full flap survival and one case exhibited partial necrosis. The follow-up periods ranged from 2 months to 38 months. We did not observe any ranges of motion limitations in the hip and knee joints of the operated leg, or any secondary complications (e.g., abscess or prolonged drainage). CONCLUSIONS: The vastus lateralis muscle-chimeric ALT free flap is a useful option for reconstructing three-dimensional lower extremity defects. PMID- 26367858 TI - Upward Translation of Cerebellar Tonsils following Surgical Expansion of Supratentorial Cranial Vault: A Unified Biomechanical Explanation of Chiari Type I. AB - Cerebellar tonsils moved significantly upward in 3 patients with Chiari type I who underwent supratentorial cranial vault expansion to alleviate intracranial pressure related to multisutural craniosynostosis. The Chiari type I deformities in these patients were the biomechanical consequence of posterior fossa cerebellar disproportion caused by supratentorial craniocerebral disproportion secondary to multisutural craniosynostosis. The authors postulate that all cases of Chiari type I deformity share the sine qua non feature of posterior fossa cerebellar disproportion. PMID- 26367859 TI - Prediction of Preterm Delivery by Late Cervical Length Measurement after 24 Weeks. AB - OBJECTIVE: To examine the value of the cervical length (CL) measurement at 24-30 gestational weeks in the prediction of spontaneous preterm delivery (SPD) between 30 and 34 weeks (SPD34) and between 34 and 37 weeks (SPD37). METHODS: We performed a prospective cross-sectional study. CL was measured once by transvaginal ultrasound examination between 24 and 30 weeks. RESULTS: The study sample consisted of 1,180 low-risk singleton pregnancies. 10 women (0.85%) had a SPD34 and 60 (5.08%) had a SPD37. CL was shorter (p < 0.001) in the women who had a SPD34 (median 11 mm) compared to the women who delivered after 34 weeks (median 31 mm). CL was shorter (p < 0.001) in the women who had a SPD37 (median 22 mm) compared to the women who delivered after 37 weeks (median 31 mm). CL predicted SPD34 (OR = 0.837, R2 = 0.2768, AUC = 0.9406, p < 0.001) and SPD37 (OR = 0.907, R2 = 0.1085, AUC = 0.7584, p < 0.001). The model achieved a sensitivity of 70.0 and 38.3% for 10% false-positive rate for SPD34 and SPD37, respectively. CONCLUSIONS: CL after 24 weeks is significantly shorter in women destined to have a SPD. In low-risk singleton pregnancies CL performs very well in predicting SPD34 and adequately in predicting SPD37. PMID- 26367860 TI - The Pharmacokinetics of Biologics: A Primer. AB - Monoclonal antibodies (MAbs) exhibit complex pharmacokinetics (PK) and pharmacodynamics (PD, response) against tumor necrosis factor (TNF). Many factors impact anti-TNF MAb PK, altering MAb clearance and therefore the half-life: albumin, weight (particularly, obesity), disease (severity, stage and co morbidities) and concomitant administration of immunosuppressants (e.g. methotrexate). These factors can alter MAb exposure, impacting on the likelihood of clinical response. Formation of anti-drug antibodies (ADAs) is another potential factor that can affect MAb PK. Factors impacting the likelihood of developing ADA are classified as patient-related (concomitant immunosuppressants, prior ADA against other anti-TNF MAb) or product-related (structure, manufacturing process, aggregate formation, route of administration and dosing regimen). Repeated episodic exposure can induce ADAs, shortening the effective treatment interval. Avoiding intervals where anti-TNF MAbs are non-measurable is important for efficacy and may delay onset of ADAs. Thus, patients whose factors predispose them to having faster clearance (or short half-life) such as severe disease, low albumin or high body weight may need shorter dose intervals to reduce the likelihood of intermittent exposure. ADAs can have no effect or can impact efficacy through MAb binding, thus inhibiting its function or potentially causing hypersensitivity reactions (PD). ADA can also increase MAb clearance (PK). Because of their impact on MAb clearance, ADAs have been linked to lower serum drug concentrations, potentially negatively impacting clinical response. ADAs have been reported for biologics in most therapeutic areas. ADAs are well documented in clinical studies due to the Food and Drug Administration and the European Medicines Agency recommendations regarding testing and impact of immunogenicity. Lastly, the dose metrics (e.g. mg vs. mg/kg) can cause issues as well. MAbs such as infliximab are dosed on a mg/kg basis, which commonly results in low concentrations in patients with low body weight. Conversely MAbs such as adalimumab are administered as a flat (mg) dose, which can result in low concentrations in high weight patients. PMID- 26367861 TI - The effect of exercise mode on the acute response of satellite cells in old men. AB - AIM: A dysregulation of satellite cells may contribute to the progressive loss of muscle mass that occurs with age; however, older adults retain the ability to activate and expand their satellite cell pool in response to exercise. The modality of exercise capable of inducing the greatest acute response is unknown. We sought to characterize the acute satellite cell response following different modes of exercise in older adults. METHODS: Sedentary older men (n = 22; 67 +/- 4 years; 27 +/- 2.6 kg*m(-2) ) were randomly assigned to complete an acute bout of either resistance exercise, high-intensity interval exercise on a cycle ergometer or moderate-intensity aerobic exercise. Muscle biopsies were obtained before, 24 and 48 h following each exercise bout. The satellite cell response was analysed using immunofluorescent microscopy of muscle cross sections. RESULTS: Satellite cell expansion associated with type I fibres was observed 24 and 48 h following resistance exercise only (P ? 0.05), while no expansion of type II-associated satellite cells was observed in any group. There was a greater number of activated satellite cells 24 h following resistance exercise (pre: 1.3 +/- 0.1, 24 h: 4.8 +/- 0.5 Pax7 + /MyoD+cells/100 fibres) and high-intensity interval exercise (pre: 0.7 +/- 0.3, 24 h: 3.1 +/- 0.3 Pax7 + /MyoD+cells/100 fibres) (P ? 0.05). The percentage of type I-associated SC co-expressing MSTN was reduced only in the RE group 24 h following exercise (pre: 87 +/- 4, 24 h: 57 +/- 5%MSTN+ type I SC) (P < 0.001). CONCLUSION: Although resistance exercise is the most potent exercise type to induce satellite cell pool expansion, high-intensity interval exercise was also more potent than moderate-intensity aerobic exercise in inducing satellite cell activity. PMID- 26367863 TI - Error, Power, and Blind Sentinels: The Statistics of Seagrass Monitoring. AB - We derive statistical properties of standard methods for monitoring of habitat cover worldwide, and criticize them in the context of mandated seagrass monitoring programs, as exemplified by Posidonia oceanica in the Mediterranean Sea. We report the novel result that cartographic methods with non-trivial classification errors are generally incapable of reliably detecting habitat cover losses less than about 30 to 50%, and the field labor required to increase their precision can be orders of magnitude higher than that required to estimate habitat loss directly in a field campaign. We derive a universal utility threshold of classification error in habitat maps that represents the minimum habitat map accuracy above which direct methods are superior. Widespread government reliance on blind-sentinel methods for monitoring seafloor can obscure the gradual and currently ongoing losses of benthic resources until the time has long passed for meaningful management intervention. We find two classes of methods with very high statistical power for detecting small habitat cover losses: 1) fixed-plot direct methods, which are over 100 times as efficient as direct random-plot methods in a variable habitat mosaic; and 2) remote methods with very low classification error such as geospatial underwater videography, which is an emerging, low-cost, non-destructive method for documenting small changes at millimeter visual resolution. General adoption of these methods and their further development will require a fundamental cultural change in conservation and management bodies towards the recognition and promotion of requirements of minimal statistical power and precision in the development of international goals for monitoring these valuable resources and the ecological services they provide. PMID- 26367862 TI - A Yoga Strengthening Program Designed to Minimize the Knee Adduction Moment for Women with Knee Osteoarthritis: A Proof-Of-Principle Cohort Study. AB - People with knee osteoarthritis may benefit from exercise prescriptions that minimize knee loads in the frontal plane. The primary objective of this study was to determine whether a novel 12-week strengthening program designed to minimize exposure to the knee adduction moment (KAM) could improve symptoms and knee strength in women with symptomatic knee osteoarthritis. A secondary objective was to determine whether the program could improve mobility and fitness, and decrease peak KAM during gait. The tertiary objective was to evaluate the biomechanical characteristics of this yoga program. In particular, we compared the peak KAM during gait with that during yoga postures at baseline. We also compared lower limb normalized mean electromyography (EMG) amplitudes during yoga postures between baseline and follow-up. Primary measures included self-reported pain and physical function (Knee injury and Osteoarthritis Outcome Score) and knee strength (extensor and flexor torques). Secondary measures included mobility (six minute walk, 30-second chair stand, stair climbing), fitness (submaximal cycle ergometer test), and clinical gait analysis using motion capture synchronized with electromyography and force measurement. Also, KAM and normalized mean EMG amplitudes were collected during yoga postures. Forty-five women over age 50 with symptomatic knee osteoarthritis, consistent with the American College of Rheumatology criteria, enrolled in our 12-week (3 sessions per week) program. Data from 38 were analyzed (six drop-outs; one lost to co-intervention). Participants experienced reduced pain (mean improvement 10.1-20.1 normalized to 100; p<0.001), increased knee extensor strength (mean improvement 0.01 Nm/kg; p = 0.004), and increased flexor strength (mean improvement 0.01 Nm/kg; p = 0.001) at follow-up compared to baseline. Participants improved mobility on the six-minute walk (mean improvement 37.7 m; p<0.001) and 30-second chair stand (mean improvement 1.3; p = 0.006) at follow-up compared to baseline. Fitness and peak KAM during gait were unchanged between baseline and follow-up. Average KAM during the yoga postures were lower than that of normal gait. Normalized mean EMG amplitudes during yoga postures were up to 31.0% of maximum but did not change between baseline and follow-up. In this cohort study, the yoga-based strengthening postures that elicit low KAMs improved knee symptoms and strength in women with knee OA following a 12 week program (3 sessions per week). The program also improved mobility, but did not improve fitness or reduce peak KAM during gait. The KAM during the yoga postures were lower than that of normal gait. Overall, the proposed program may be useful in improving pain, strength, and mobility in women with knee osteoarthritis. Clinical efficacy needs to be assessed using a randomized controlled trial design. TRIAL REGISTRATION: ClinicalTrials.gov NCT02146105. PMID- 26367864 TI - MRN- and 9-1-1-Independent Activation of the ATR-Chk1 Pathway during the Induction of the Virulence Program in the Phytopathogen Ustilago maydis. AB - DNA damage response (DDR) leads to DNA repair, and depending on the extent of the damage, to further events, including cell death. Evidence suggests that cell differentiation may also be a consequence of the DDR. During the formation of the infective hypha in the phytopathogenic fungus Ustilago maydis, two DDR kinases, Atr1 and Chk1, are required to induce a G2 cell cycle arrest, which in turn is essential to display the virulence program. However, the triggering factor of DDR in this process has remained elusive. In this report we provide data suggesting that no DNA damage is associated with the activation of the DDR during the formation of the infective filament in U. maydis. We have analyzed bulk DNA replication during the formation of the infective filament, and we found no signs of impaired DNA replication. Furthermore, using RPA-GFP fusion as a surrogate marker of the presence of DNA damage, we were unable to detect any sign of DNA damage at the cellular level. In addition, neither MRN nor 9-1-1 complexes, both instrumental to transmit the DNA damage signal, are required for the induction of the above mentioned cell cycle arrest, as well as for virulence. In contrast, we have found that the claspin-like protein Mrc1, which in other systems serves as scaffold for Atr1 and Chk1, was required for both processes. We discuss possible alternative ways to trigger the DDR, independent of DNA damage, in U. maydis during virulence program activation. PMID- 26367865 TI - Glial Attenuation With Ibudilast in the Treatment of Medication Overuse Headache: A Double-Blind, Randomized, Placebo-Controlled Pilot Trial of Efficacy and Safety. AB - BACKGROUND: Medication overuse headache (MOH) is a condition bordering between a chronic pain condition and a substance dependence disorder. Activation of immunocompetent glial cells in the central nervous system has been linked to both pathological pain and drug addiction/reward. Preclinically, ibudilast attenuates glial activation and is able to reduce neuropathic pain and markers of substance dependence. We therefore hypothesized ibudilast would reduce headache burden and opioid analgesic requirements in patients with opioid overuse headache. OBJECTIVE: To determine if treatment with ibudilast provides a greater reduction in headache index than placebo in MOH patients consuming opioids. METHODS: Participants with MOH who were using opioids were randomized via computer generated code to ibudilast 40 mg or placebo twice daily for 8 weeks in a double blind, parallel groups study. Before randomization participants completed a 4 week baseline headache diary. During treatment, headache diary data collection continued and participants attended 4 study visits during which quantitative sensory testing was performed. Blood samples for immune biomarker analyses were collected before and after treatment in a subgroup of participants. RESULTS: Thirty-four participants were randomized, 13 of 15 randomized to ibudilast and 17 of 19 randomized to placebo completed treatment. Ibudilast was generally well tolerated with mild, transient nausea reported as the most common adverse event (66.7% vs 10.5% in placebo group). Results are shown as mean (SD). At the end of treatment no differences in the primary outcome average daily headache index (placebo 62 [44] vs ibudilast 77 [72] groups, difference -15, CI -65 to 35 h * numerical rating scale), or secondary outcomes headache frequency (placebo 23 [8.1] vs ibudilast 24.5 [6.2], difference -1.5, CI -7.7 to 4.8 days/month) and opioid intake (placebo 20.6 [43] vs ibudilast 19 [24.3], difference 1.6, CI -31.5 to 34.8 mg morphine equivalent) were observed between placebo and ibudilast groups. CONCLUSIONS: Using the current dosing regimen, ibudilast does not improve headache or reduce opioid use in patients with MOH without mandated opioid withdrawal. However, it would be of interest to determine in future trials if ibudilast is able to improve ease of withdrawal during a forced opioid down titration when incorporated into an MOH detoxification program. PMID- 26367866 TI - MUC1 Predicts Colorectal Cancer Metastasis: A Systematic Review and Meta-Analysis of Case Controlled Studies. AB - OBJECTIVE: To evaluate the predicting value of MUC1 expression in lymph node and distant metastasis of colorectal cancer (CRC). METHODS: Pubmed/ MEDLINE and EMBASE were searched to identify eligible studies that evaluated the correlation between MUC1 and CRC. A meta-analysis was conducted to evaluate the impact of MUC1 expression on CRC metastasis. RESULTS: A total of 18 studies (n = 3271) met inclusion criteria and the mean Newcastle-Ottawa Scale (NOS) score was 6.3 with a range from 4 to 8. The pooled OR in the meta-analysis of 15 studies indicated that positive MUC1 expression correlated with more CRC node metastasis (OR = 2.32, 95% CI = 1.63-3.29). The data synthesis of 6 studies suggested that MUC1 expression predicted more possibility of CRC distant metastasis (OR = 2.22, 95% CI = 1.23-4.00). In addition, the combined OR of 7 studies showed that MUC1 expression indicated higher Duke's stage (OR = 3.02, 95% CI = 2.11-4.33). No publication bias was found in the mate-analysis by Begg's test or Egger's test with the exception of the meta-analysis of MUC1 with CRC node metastasis (Begg's test p = 0.729, Egger's test p = 0.000). CONCLUSIONS: Despite of some modest bias, the pooled evidence suggested that MUC1 expression was significantly correlated with CRC metastasis. PMID- 26367867 TI - STEMI patients and nonculprit lesions: To treat or not to treat? and when? A review of most recent literature. AB - Patients with ST segment elevation myocardial infarction and multivessel disease represent a high percentage of ischemic patient with a worse outcome than patient with single coronary artery disease. Therefore, initial management of these patients is of high importance, but unfortunately this is not clarified yet. We analyze the available literature trying to afford current doubts to determine which way of revascularization is to be preferred. (c) 2015 Wiley Periodicals, Inc. PMID- 26367868 TI - Quantum Dots Reveal Shifts in Organic Nitrogen Uptake by Fungi Exposed to Long Term Nitrogen Enrichment. AB - Anthropogenic nitrogen (N) enrichment can alter N dynamics associated with decomposing plant litter. However, it is unclear to what extent these alterations occur via microbial effects (e.g., changes in gene regulation, physiology, or community composition) versus plant litter effects (e.g., changes in composition of N and C compounds). To isolate microbial effects from plant litter effects, we collected plant litter from long-term N fertilized and control plots, reciprocally inoculated it with microbes from the two treatments, and incubated it in a common field setting for three months. We used quantum dots (QDs) to track fungal uptake of glycine and chitosan. Glycine is a relatively simple organic N compound; chitosan is more complex. We found that microbial and litter origins each contributed to a shift in fungal uptake capacities under N fertilization. Specifically, N fungi preferred glycine over chitosan, but control fungi did not. In comparison, litter effects were more subtle, and manifested as a three-way interaction between litter origin, microbial origin, and type of organic N (glycine versus chitosan). In particular, control fungi tended to target chitosan only when incubated with control litter, while N fungi targeted glycine regardless of litter type. Overall, microbial effects may mediate how N dynamics respond to anthropogenic N enrichment in ecosystems. PMID- 26367869 TI - Embryonic Lethality Due to Arrested Cardiac Development in Psip1/Hdgfrp2 Double Deficient Mice. AB - Hepatoma-derived growth factor (HDGF) related protein 2 (HRP2) and lens epithelium-derived growth factor (LEDGF)/p75 are closely related members of the HRP2 protein family. LEDGF/p75 has been implicated in numerous human pathologies including cancer, autoimmunity, and infectious disease. Knockout of the Psip1 gene, which encodes for LEDGF/p75 and the shorter LEDGF/p52 isoform, was previously shown to cause perinatal lethality in mice. The function of HRP2 was by contrast largely unknown. To learn about the role of HRP2 in development, we knocked out the Hdgfrp2 gene, which encodes for HRP2, in both normal and Psip1 knockout mice. Hdgfrp2 knockout mice developed normally and were fertile. By contrast, the double deficient mice died at approximate embryonic day (E) 13.5. Histological examination revealed ventricular septal defect (VSD) associated with E14.5 double knockout embryos. To investigate the underlying molecular mechanism(s), RNA recovered from ventricular tissue was subjected to RNA sequencing on the Illumina platform. Bioinformatic analysis revealed several genes and biological pathways that were significantly deregulated by the Psip1 knockout and/or Psip1/Hdgfrp2 double knockout. Among the dozen genes known to encode for LEDGF/p75 binding factors, only the expression of Nova1, which encodes an RNA splicing factor, was significantly deregulated by the knockouts. However the expression of other RNA splicing factors, including the LEDGF/p52-interacting protein ASF/SF2, was not significantly altered, indicating that deregulation of global RNA splicing was not a driving factor in the pathology of the VSD. Tumor growth factor (Tgf) beta-signaling, which plays a key role in cardiac morphogenesis during development, was the only pathway significantly deregulated by the double knockout as compared to control and Psip1 knockout samples. We accordingly speculate that deregulated Tgf-beta signaling was a contributing factor to the VSD and prenatal lethality of Psip1/Hdgfrp2 double-deficient mice. PMID- 26367871 TI - Convex-Envelope Based Automated Quantitative Approach to Multi-Voxel 1H-MRS Applied to Brain Tumor Analysis. AB - BACKGROUND: Magnetic Resonance Spectroscopy (MRS) can measure in vivo brain tissue metabolism that exhibits unique biochemical characteristics in brain tumors. For clinical application, an efficient and versatile quantification method of MRS would be an important tool for medical research, particularly for exploring the scientific problem of tumor monitoring. The objective of our study is to propose an automated MRS quantitative approach and assess the feasibility of this approach for glioma grading, prognosis and boundary detection. METHODS: An automated quantitative approach based on a convex envelope (AQoCE) is proposed in this paper, including preprocessing, convex-envelope based baseline fitting, bias correction, sectional baseline removal, and peak detection, in a total of 5 steps. Some metabolic ratios acquired by this quantification are selected for statistical analysis. An independent sample t-test and the Kruskal-Wallis test are used for distinguishing low-grade gliomas (LGG) and high-grade gliomas (HGG) and for detecting the tumor, peritumoral and contralateral areas, respectively. Seventy-eight cases of pre-operative brain gliomas with pathological reports are included in this study. RESULTS: Cho/NAA, Cho/Cr and Lip-Lac/Cr (LL/Cr) calculated by AQoCE in the tumor area differ significantly between LGG and HGG, with p<=0.005. Using logistic regression combining Cho/NAA, Cho/Cr and LL/Cr to generate a ROC curve, AQoCE achieves a sensitivity of 92.9%, a specificity of 72.2%, and an area under ROC curve (AUC) of 0.860. Moreover, both Cho/NAA and Cho/Cr in the AQoCE approach show a significant difference (p<=0.019) between tumoral, peritumoral, and contralateral areas. The comparison between the results of AQoCE and Siemens MRS processing software are also discussed in this paper. CONCLUSIONS: The AQoCE approach is an automated method of residual water removal and metabolite quantification. It can be applied to multi-voxel 1H-MRS for evaluating brain glioma grading and demonstrating characteristics of brain glioma metabolism. It can also detect infiltration in the peritumoral area. Under the limited clinical data used, AQoCE is significantly more versatile and efficient compared to the reference approach of Siemens. PMID- 26367870 TI - The Role of Cysteine Residues in Redox Regulation and Protein Stability of Arabidopsis thaliana Starch Synthase 1. AB - Starch biosynthesis in Arabidopsis thaliana is strictly regulated. In leaf extracts, starch synthase 1 (AtSS1) responds to the redox potential within a physiologically relevant range. This study presents data testing two main hypotheses: 1) that specific thiol-disulfide exchange in AtSS1 influences its catalytic function 2) that each conserved Cys residue has an impact on AtSS1 catalysis. Recombinant AtSS1 versions carrying combinations of cysteine-to-serine substitutions were generated and characterized in vitro. The results demonstrate that AtSS1 is activated and deactivated by the physiological redox transmitters thioredoxin f1 (Trxf1), thioredoxin m4 (Trxm4) and the bifunctional NADPH dependent thioredoxin reductase C (NTRC). AtSS1 displayed an activity change within the physiologically relevant redox range, with a midpoint potential equal to -306 mV, suggesting that AtSS1 is in the reduced and active form during the day with active photosynthesis. Cys164 and Cys545 were the key cysteine residues involved in regulatory disulfide formation upon oxidation. A C164S_C545S double mutant had considerably decreased redox sensitivity as compared to wild type AtSS1 (30% vs 77%). Michaelis-Menten kinetics and molecular modeling suggest that both cysteines play important roles in enzyme catalysis, namely, Cys545 is involved in ADP-glucose binding and Cys164 is involved in acceptor binding. All the other single mutants had essentially complete redox sensitivity (98-99%). In addition of being part of a redox directed activity "light switch", reactivation tests and low heterologous expression levels indicate that specific cysteine residues might play additional roles. Specifically, Cys265 in combination with Cys164 can be involved in proper protein folding or/and stabilization of translated protein prior to its transport into the plastid. Cys442 can play an important role in enzyme stability upon oxidation. The physiological and phylogenetic relevance of these findings is discussed. PMID- 26367873 TI - Crocus sativus Petals: Waste or Valuable Resource? The Answer of High-Resolution and High-Resolution Magic Angle Spinning Nuclear Magnetic Resonance. AB - Intact Crocus sativus petals were studied for the first time by high-resolution magic angle spinning nuclear magnetic resonance (HR-MAS NMR) spectroscopy, revealing the presence of kinsenoside (2) and goodyeroside A (3), together with 3 hydroxy-gamma-butyrolactone (4). These findings were confirmed by HR-NMR analysis of the ethanol extract of fresh petals and showed that, even though carried out rapidly, partial hydrolysis of glucopyranosyloxybutanolides occurs during extraction. On the other hand, kaempferol 3-O-sophoroside (1), which is "NMR silent" in intact petals, is present in extracts. These results suggest to evaluate the utilization of saffron petals for phytopharmaceutical and nutraceutical purposes to exploit a waste product of massive production of commercial saffron and point to the application of HR-MAS NMR for monitoring bioactive compounds directly on intact petals, avoiding the extraction procedure and the consequent hydrolysis reaction. PMID- 26367872 TI - Prevalence of Sarcopenia and Its Relationship with Sites of Fragility Fractures in Elderly Chinese Men and Women. AB - OBJECTIVE: Sarcopenia might be associated with bone fragility in elderly individuals. This study aimed to investigate the prevalence of sarcopenia and its association with fragility fracture sites in elderly Chinese patients. METHODS: Patients (322 men and 435 women) aged 65-94 years and with a history of fragility fractures in the ankle, wrist, vertebrae or hip, and healthy men (n = 1263) and women (n = 1057) aged 65-92 years without a history of fractures were enrolled. Whole-body dual energy X-ray absorptiometry was used to analyze skeletal muscle mass index (SMI), fat mass and bone mineral density. Sarcopenia was defined as SMI less than two standard deviations below the mean of a young reference group. RESULTS: Sarcopenia occurrence varied with fracture location. Sarcopenia was more common in females with vertebral and hip fractures and in men with hip and ankle fractures than in the non-fracture group). Sarcopenia was significantly more prevalent in men with wrist, hip and ankle fractures than in women. SMI was correlated with BMD in different fracture groups. Logistic regression analyses revealed that lower SMI was associated with an increased risk of hip fracture both in men and women and ankle fracture in men. DISCUSSION: Sarcopenia may be an independent risk factor for hip and ankle fractures in men, and for hip fractures in women. PMID- 26367874 TI - Double Relapsed and/or Refractory Multiple Myeloma: Clinical Outcomes and Real World Healthcare Costs. AB - Double relapsed and/or refractory multiple myeloma (DRMM), MM that is relapsed and/or refractory to bortezomib and lenalidomide, carries a poor prognosis. The healthcare costs of DRMM have not previously been reported. We analyzed detailed medical resource utilization (MRU) costs, drug costs and outcomes for 39 UK patients receiving standard DRMM therapy. Median OS in this cohort was 5.6 months. The mean cost of DRMM treatment plus MRU until death was L23,472 [range: L1,411-L90,262], split between drug costs L11,191 and other resource use costs L12,281. The cost per assumed quality-adjusted life year (QALY) during DRMM was L66,983. These data provide a standard of care comparison when evaluating the cost-effectiveness of new drugs in DRMM. PMID- 26367875 TI - Locked by Design: A Conformationally Constrained Transglutaminase Tag Enables Efficient Site-Specific Conjugation. AB - Based on the crystal structure of a natural protein substrate for microbial transglutaminase, an enzyme that catalyzes protein crosslinking, a recognition motif for site-specific conjugation was rationally designed. Conformationally locked by an intramolecular disulfide bond, this structural mimic of a native conjugation site ensured efficient conjugation of a reporter cargo to the therapeutic monoclonal antibody cetuximab without erosion of its binding properties. PMID- 26367876 TI - Surface Relief Changes in Cholesteric Cyclosiloxane Oligomer Films at Different Temperatures. AB - The development of new approaches for the surface topography control is an important topic as the relief significantly affects physical and chemical properties of surfaces. We studied cholesteric cyclosiloxane oligomeric films on which surface focal conic domains with double-helix pattern were observed by means of AFM. In situ investigation of the dependence of the films topography on temperature showed that the surface relief formation can be effectively managed by varying conditions of thermal treatment. Obtained structures can be frozen by cooling the films below glass-transition temperature. PMID- 26367877 TI - Simplified modelling the mode instability threshold of high power fiber amplifiers in the presence of photodarkening. AB - In this paper we present a simple model to predict the behavior of the transversal mode instability threshold when different parameters of a fiber amplifier system are changed. The simulation model includes an estimation of the photodarkening losses which shows the strong influence that this effect has on the mode instability threshold and on its behavior. Comparison of the simulation results with experimental measurements reveal that the mode instability threshold in a fiber amplifier system is reached for a constant average heat load value in good approximation. Based on this model, the expected behavior of the mode instability threshold when changing the seed wavelength, the seed power and/or the fiber length will be presented and discussed. Additionally, guidelines for increasing the average power of fiber amplifier systems will be provided. PMID- 26367878 TI - Two-port multimode interference reflectors based on aluminium mirrors in a thick SOI platform. AB - Multimode interference reflectors (MIRs) were recently introduced as a new type of photonic integrated devices for on-chip, broadband light reflection. In the original proposal, different MIRs were demonstrated based on total internal reflection mirrors made of two deep-etched facets. Although simpler to fabricate, this approach imposes certain limits on the shape of the field pattern at the reflecting facets, which in turn restricts the types of MIRs that can be implemented. In this work, we propose and experimentally demonstrate the use of aluminium-based mirrors for the design of 2-port MIRs with variable reflectivity. These mirrors do not impose any restrictions on the incident field, and thus give more flexibility at the design stage. Devices with different reflectivities in the range between 0 and 0.5 were fabricated in a 3 um thick SOI platform, and characterization of multiple dies was performed to extract statistical data about their performance. Our measurements show that, on average, losses both in the aluminium mirror and in the access waveguides reduce the reflectivities to about 79% of their target value. Moreover, standard deviations lower than +/-5% are obtained over a 20 nm wavelength range (1540-1560 nm). We also provide a theoretical model of the aluminium mirror based on the effective index method and Fresnel equations in multilayer thin films, which shows good agreement with FDTD simulations. PMID- 26367879 TI - Adaptive tool servo diamond turning for enhancing machining efficiency and surface quality of freeform optics. AB - Fast tool servo/ slow tool servo (FTS/STS) diamond turning is a very promising technique for the generation of freeform optics. However, the currently adopted constant scheme for azimuth sampling and side-feeding motion possesses no adaptation to surface shape variation, leading to the non-uniform surface quality and low machining efficiency. To overcome this defect, this paper reports on a novel adaptive tool servo (ATS) diamond turning technique which is essentially based on the novel two-degree-of-freedom (2-DOF) FTS/STS. In the ATS, the sampling interval and the side-feeding motion are actively controlled at any cutting point to adapt the machining process to shape variation of the desired surface, making both the sampling induced interpolation error and the side feeding induced residual tool mark be within the desired tolerances. Characteristic of the required cutting motion suggests that besides the conventional z-axis servo motion, another servo motion along the x-axis synthesizing by the c-axis is mandatory for implementing the ATS. Comparative studies of surface generation of typical micro-structured surfaces in FTS/STS and ATS are thoroughly conducted both theoretically and experimentally. The result demonstrates that the ATS outperforms the FTS/STS with improved surface quality while simultaneously enhanced machining efficiency. PMID- 26367880 TI - 28 Gb/s duobinary signal transmission over 40 km based on 10 GHz DML and PIN for 100 Gb/s PON. AB - In this paper, we demonstrate the direct modulation and direct detection of 28 Gb/s duobinary signal for the future downstream capacity upgrade in next generation passive optical network (PON). Commercial 10-GHz directly modulated laser (DML) and PIN with a combined modulation bandwidth of ~7 GHz are used as transmitter and receiver respectively. In order to mitigate the chromatic dispersion induced signal distortion, an optical delay interferometer (DI) is employed to narrow down the signal spectrum, thereby realizing 40-km single mode fiber (SMF) transmission in C-band. Besides, the chirp-induced spectral broadening of the directly modulated signal enables a higher launch power than external modulation schemes, which increases the loss budget of the system. As a result, 31-dB loss budget is achieved, supporting 64 users with 40-km reach. Also, as the transceivers in both optical line terminal (OLT) and optical network unit (ONU) are commercial l0-GHz devices, the proposed scheme is compatible with 40-Gb/s time and wavelength division multiplexing passive optical network (TWDM PON) systems, providing a cost-efficient alternative for the development of 100G PON. PMID- 26367881 TI - Multi-wavelength in-band OSNR monitor based on Lyot-Sagnac interferometer. AB - A novel in-band OSNR monitor is proposed and experimentally demonstrated for WDM signal. By using a Lyot-Sagnac interferometer, the monitor realized OSNR measurement from 7.5~25 dB (within an accuracy of +/- 0.5 dB) for 4-channel 40 Gbaud NRZ-QPSK signals, without requirement for prior knowledge of the noise-free coherence properties of signal. Further investigation proved that this OSNR monitor had high tolerance to chromatic dispersion (0~1152 ps/nm), first-order polarization mode dispersion (0~100 ps), and polarized noise. Moreover, the monitor worked very well even with input optical power as low as -8.24 dBm, and also worked in in C-band. Theoretical analysis and experimental results prove that it is capable of measuring OSNR for polarization-division-multiplexing signals. PMID- 26367882 TI - Wavefront reconstruction algorithm based on Legendre polynomials for radial shearing interferometry over a square area and error analysis. AB - Based on the Legendre polynomials expressions and its properties, this article proposes a new approach to reconstruct the distorted wavefront under test of a laser beam over square area from the phase difference data obtained by a RSI system. And the result of simulation and experimental results verifies the reliability of the method proposed in this paper. The formula of the error propagation coefficients is deduced when the phase difference data of overlapping area contain noise randomly. The matrix T which can be used to evaluate the impact of high-orders Legendre polynomial terms on the outcomes of the low-order terms due to mode aliasing is proposed, and the magnitude of impact can be estimated by calculating the F norm of the T. In addition, the relationship between ratio shear, sampling points, terms of polynomials and noise propagation coefficients, and the relationship between ratio shear, sampling points and norms of the T matrix are both analyzed, respectively. Those research results can provide an optimization design way for radial shearing interferometry system with the theoretical reference and instruction. PMID- 26367883 TI - 615 nm GaInNAs VECSEL with output power above 10 W. AB - A high-power optically-pumped vertical-external-cavity surface-emitting laser (VECSEL) generating 10.5 W of cw output power at 615 nm is reported. The gain mirror incorporated 10 GaInNAs quantum wells and was designed to have an emission peak in the 1230 nm range. The fundamental emission was frequency doubled to the red spectral range by using an intra-cavity nonlinear LBO crystal. The maximum optical-to-optical conversion efficiency was 17.5%. The VECSEL was also operated in pulsed mode by directly modulating the pump laser to produce light pulses with duration of ~1.5 us. The maximum peak power for pulsed operation (pump limited) was 13.8 W. This corresponded to an optical-to-optical conversion efficiency of 20.4%. PMID- 26367884 TI - Mid-infrared wavelength multiplexer in InGaAs/InP waveguides using a Rowland circle grating. AB - We report the monolithic integration of a 15-channel multiplexer on indium phosphide. It covers the 7.1-to-8.5 um wavelength range suitable for combining the outputs of several individual lasers. The fabrication is compatible with the growth of active layers, therefore enabling a fully integrate broadband laser source in the mid-infrared spectral range. Channels are accurately spaced in wavelength (97 nm) in good agreement with design. PMID- 26367885 TI - Exploring the effect of diffuse reflection on indoor localization systems based on RSSI-VLC. AB - This work explores and evaluates the effect of diffuse light reflection on the accuracy of indoor localization systems based on visible light communication (VLC) in a high reflectivity environment using a received signal strength indication (RSSI) technique. The effect of the essential receiver (Rx) and transmitter (Tx) parameters on the localization error with different transmitted LED power and wall reflectivity factors is investigated at the worst Rx coordinates for a directed/overall link. Since this work assumes harsh operating conditions (i.e., a multipath model, high reflectivity surfaces, worst Rx position), an error of >= 1.46 m is found. To achieve a localization error in the range of 30 cm under these conditions with moderate LED power (i.e., P = 0.45 W), low reflectivity walls (i.e., rho = 0.1) should be used, which would enable a localization error of approximately 7 mm at the room's center. PMID- 26367886 TI - Sensing analysis based on plasmon induced transparency in nanocavity-coupled waveguide. AB - We report the sensing characteristic based on plasmon induced transparency in nanocavity-coupled metal-dielectric-metal waveguide analytically and numerically. A simple model for the sensing nature is first presented by the coupled mode theory. We show that the coupling strength and the resonance detuning play important roles in optimizing the sensing performance and the detection limit of sensor, and an interesting double-peak sensing is also obtained in such plasmonic sensor. In addition, the specific refractive index width of the dielectric environment is discovered in slow-light sensing and the relevant sensitivity can be enhanced. The proposed model and findings provide guidance for fundamental research of the integrated plasmonic nanosensor applications and designs. PMID- 26367887 TI - Narrow-linewidth microwave generation using AlGaInAs/InP microdisk lasers subject to optical injection and optoelectronic feedback. AB - Narrow-linewidth and low phase noise photonic microwave generation under sideband injection locking are demonstrated using an 8-MUm-radius AlGaInAs/InP microdisk laser subject to optical injection and optoelectronic feedback. Microdisk laser subject to external optical injection at the period-one state provides the microwave subcarrier seed signal, and the optoelectronic feedback serves as direct current modulation to stabilize and lock the generated microwave signal without using the electrical filter. High-quality photonic microwave signals are realized with the 3-dB linewidth of less than 1 kHz and the frequency tunable range from 8.8 to 17 GHz. Single sideband phase noise of -101 dBc/Hz is obtained at a frequency offset of 10 kHz for the generated 14.7 GHz signal. Furthermore, the dependences of photonic microwave signal on the optical injection and optoelectronic feedback parameters are investigated. PMID- 26367888 TI - Studies of sub-millisecond domain dynamics in periodically poled Rb-doped KTiOPO(4), using online in situ second harmonic generation. AB - The temporal evolution of in situ second-harmonic generation was employed to study domain dynamics during periodic poling in Rb-doped KTP. With this method we investigated the influence of various poling parameters, including electric-field pulse shape, pulse magnitude, and number of pulses, on the quality of the QPM structure. It was found that the grating formation can be a sub-millisecond process and the benefits of using symmetric triangular electric-field pulse shape over square pulse shape in the single-pulse poling regime were demonstrated. Multiple-pulse poling with triangular pulses was shown to have a detrimental effect on the QPM structure quality, while multiple square pulses can provide additional flexibility to the structuring process. PMID- 26367889 TI - Light-extraction efficiency control in AlGaN-based deep-ultraviolet flip-chip light-emitting diodes: a comparison to InGaN-based visible flip-chip light emitting diodes. AB - We study light-extraction efficiency (LEE) of AlGaN-based deep-ultraviolet light emitting diodes (DUV-LEDs) using flip-chip (FC) devices with varied thickness in remaining sapphire substrate by experimental output power measurement and computational methods using 3-dimensional finite-difference time-domain (3D-FDTD) and Monte Carlo ray-tracing simulations. Light-output power of DUV-FCLEDs compared at a current of 20 mA increases with thicker sapphire, showing higher LEE for an LED with 250-MUm-thick sapphire by ~39% than that with 100-MUm-thick sapphire. In contrast, LEEs of visible FCLEDs show only marginal improvement with increasing sapphire thickness, that is, ~6% improvement for an LED with 250-MUm thick sapphire. 3D-FDTD simulation reveals a mechanism of enhanced light extraction with various sidewall roughness and thickness in sapphire substrates. Ray tracing simulation examines the light propagation behavior of DUV-FCLED structures. The enhanced output power and higher LEE strongly depends on the sidewall roughness of the sapphire substrate rather than thickness itself. The thickness starts playing a role only when the sapphire sidewalls become rough. The roughened surface of sapphire sidewall during chip-separation process is critical for TM-polarized photons from AlGaN quantum wells to escape in lateral directions before they are absorbed by p-GaN and Au-metal. Furthermore, the ray tracing results show a reasonably good agreement with the experimental result of the LEE. PMID- 26367890 TI - Ultra-compact LED lens with double freeform surfaces for uniform illumination. AB - An ultra-compact rotational symmetric lens with double freeform surfaces based on the edge-ray principle is designed in this paper. The lens redistributes light emitting from a Lambertian LED light source to achieve uniform illumination within the target area. The initial design is optimized for optics compactness under structural constraints and illumination requirement using the genetic algorithm. A design for the double-freeform-surface lens with a height of the optics system h = 12.56 mm for a circular LED source with a diameter D = 10 mm is demonstrated for uniform illumination within 45 degrees and thus achieves optics compactness h/D = 1.256, which is half of that achieved by the single-freeform surface lens. The Monte-Carlo ray-tracing result shows an illumination circular area with a clear cut-off at R = 1000 mm at the target plane in a distance H = 1000 mm. The uniformity within the target illumination area is greater than 0.9 and the light output efficiency is as high as 0.9865. PMID- 26367891 TI - New approach for extraordinary transmission through an array of subwavelength apertures using thin ENNZ metamaterial liners. AB - Extraordinary transmission (ET) through a periodic array of subwavelength apertures on a perfect metallic screen has been studied extensively in recent years, and has largely been attributed to diffraction effects, for which the periodicity of the apertures, rather than their dimensions, dominates the response. The transmission properties of the apertures at resonance, on the other hand, are not typically considered 'extraordinary' because they may be explained using more conventional aperture-theoretical mechanisms. This work describes a novel approach for achieving ET in which subwavelength apertures are made to resonate by lining them using thin, epsilon-negative and near-zero (ENNZ) metamaterials. The use of ENNZ metamaterials has recently proven successful in miniaturizing circular waveguides by strongly reducing their natural cutoff frequencies, and the theory is adapted here for the design of subwavelength apertures in a metallic screen. We present simulations and proof-of-concept measurements at microwave frequencies that demonstrate ET for apertures measuring one-quarter of a wavelength in diameter and suggest the potential for even more dramatic miniaturization simply by engineering the ENNZ metamaterial dispersion. The results exhibit a fano-like profile whose frequency varies with the properties of the metamaterial liner, but is independent of period. It is suggested that similar behaviour can be obtained at optical frequencies, where ENNZ metamaterials may be realized using appropriately arranged chains of plasmonic nanoparticles. PMID- 26367892 TI - Far-infrared absorber based on standing-wave resonances in metal-dielectric-metal cavity. AB - Thin-film resonant absorbers for the far-IR spectral range were fabricated, characterized, and modeled. The 3-MUm-thick structure comprises a periodic surface array of metal squares, a dielectric spacer and a metallic ground plane. Up to 95% absorption for the fundamental band at ~53.5MUm wavelength (5.6 THz) is achieved experimentally. Absorption bands are independent of the structure period and only weakly dependent on polarization and incident angle. The results are well explained in terms of standing-wave resonances within individual metal dielectric-metal cavities. The structure has application as a wavelength selective coating for far-IR bolometers. PMID- 26367893 TI - Capacity limits of systems employing multiple optical phase conjugators. AB - We extend the theory of parametric noise amplification to the case of transmission systems employing multiple optical phase conjugators, demonstrating that the excess noise due to this process may be reduced in direct proportion to the number of phase conjugation devices employed. We further identify that the optimum noise suppression is achieved for an odd number of phase conjugators, and that the noise may be further suppressed by up to 3dB by partial digital back propagation (or fractional spans at the ends of the links). PMID- 26367894 TI - Lasing induced by resonant absorption. AB - We theoretically demonstrate that increase of absorption with constant gain in laser systems can lead to onset of laser generation. This counterintuitive absorption induced lasing (AIL) is explained by emergence of additional lasing modes created by an introduction of an absorbing medium with narrow linewidth. We show that this effect is universal and, in particular, can be encountered in simple Fabry-Perot-like systems and doped spherical dielectric nanoresonators. The predicted behavior is robust against detuning between the resonant frequencies of gain and absorbing medium. PMID- 26367895 TI - Simulation of a partially depleted absorber (PDA) photodetector. AB - We use a 2D drift-diffusion model to study the nonlinear response of a partially depleted absorber (PDA) phododetector. The model includes external loading, incomplete ionization, the Franz-Keldysh effect, and history-dependent impact ionization. It also takes into account heat flow in the device. With all these effects included, we obtain excellent agreement with experiments for the responsivity and for the harmonic power at different modulation frequencies. The role of these different physical effects is elucidated, and we find that both the Franz-Keldysh effect and the load resistance play a key role in generating higher harmonic power at larger reverse biases. Increasing the size of the p-region absorption layers reduces the impact of the Franz-Keldysh effect. Decreasing the effective load resistance also decreases the higher harmonic powers. We also show that the model can suggest design changes that will improve device performance. PMID- 26367896 TI - Broadly, independent-tunable, dual-wavelength mid-infrared ultrafast optical parametric oscillator. AB - We demonstrate a two-crystal mid-infrared dual-wavelength optical parametric oscillator, synchronously pumped by a high power femtosecond Yb:fiber laser. The singly-resonant ring cavity, containing two periodically poled lithium niobate crystals, is capable of generating two synchronized idler wavelengths, independently tunable over 30 THz in the 2.9 - 4.2 MUm wavelength region, due to the cascaded quadratic nonlinear effect. The independent tunability of the two idlers makes the optical parametric oscillator a promising source for ultrafast pulse generation towards the THz wavelength region, based on different frequency generation. In addition, the observed frequency doubled idler within the crystal indicates the possibility to realize a broadband optical self-phase locking between pump, signal, idler and higher order generated parametric lights. PMID- 26367897 TI - Generalized Jones matrix method for homogeneous biaxial samples. AB - The generalized Jones matrix (GJM) is a recently introduced tool to describe linear transformations of three-dimensional light fields. Based on this framework, a specific method for obtaining the GJM of uniaxial anisotropic media was recently presented. However, the GJM of biaxial media had not been tackled so far, as the previous method made use of a simplified rotation matrix that lacks a degree of freedom in the three-dimensional rotation, thus being not suitable for calculating the GJM of biaxial media. In this work we propose a general method to derive the GJM of arbitrarily-oriented homogeneous biaxial media. It is based on the differential generalized Jones matrix (dGJM), which is the three-dimensional counterpart of the conventional differential Jones matrix. We show that the dGJM provides a simple and elegant way to describe uniaxial and biaxial media, with the capacity to model multiple simultaneous optical effects. The practical usefulness of this method is illustrated by the GJM modeling of the polarimetric properties of a negative uniaxial KDP crystal and a biaxial KTP crystal for any three-dimensional sample orientation. The results show that this method constitutes an advantageous and straightforward way to model biaxial media, which show a growing relevance for many interesting applications. PMID- 26367898 TI - Giant nonlocal lossless permittivity at optical frequencies. AB - We show how to achieve a giant permittivity combined with negligible losses in both the visible and the near-IR for composites made of alternating layers of plasmonic and gain materials as the electric field is directed normally to the layers. The effects of nonlocality are taken into account that makes the method quite realistic. Solving the dispersion equation for eigenmodes of an infinite layered composite, we show that both propagating and nonpropagating modes can be excited, that leads to the realization of a giant nonlocal permittivity. Both phase and group velocities for the propagating eigenmode have been calculated showing that slow light can be achieved in the system under study. The results obtained open new possibilities for designing nanolaser, slow-light, superresolution imaging devices, etc. PMID- 26367899 TI - Frequency tunable optoelectronic oscillator based on a directly modulated DFB semiconductor laser under optical injection. AB - A frequency tunable optoelectronic oscillator based on a directly modulated distributed-feedback (DFB) semiconductor laser under optical injection is proposed and experimentally demonstrated. Through optical injection, the relaxation oscillation frequency of the DFB laser is enhanced and its high modulation efficiency can enable the loop oscillation with a RF threshold gain of less than 20 dB. The DFB laser is a commercial semiconductor laser with a package of 10 GHz, and its packaging limitation can be overcome by optical injection. In our scheme, neither a high-speed external modulator nor an electrical bandpass filter is required, making the system simple and low-cost. Microwave signals with a frequency tuning range from 5.98 to 15.22 GHz are generated by adjusting the injection ratio and frequency detuning between the master and slave lasers. The phase noise of the generated 9.75 GHz microwave signal is measured to be -104.8 dBc/Hz @ 10 kHz frequency offset. PMID- 26367900 TI - Exploring binary and ternary modulations on a PA-LCoS device for holographic data storage in a PVA/AA photopolymer. AB - We focus on the novelty of three elements in holographic data storage systems (HDSS): the data pager, where we introduce a parallel-aligned liquid crystal on silicon (PA-LCoS) microdisplay; the recording material, where we consider the highly versatile PVA/AA photopolymer; and also in the architecture of the object arm, where a convergent correlator system is introduced. We show that PA-LCoS devices cannot implement pure hybrid-ternary modulated (HTM) data pages but a rather close approximation. Validation of the HDSS expressions for the convergent correlator and comparison with the widespread 4-f system is performed. Experimental results with PVA/AA material showing bit-error rates (BER) in the range of 10-3, further show its potential application for HDSS, and also demonstrate the validity of the testing platform and PA-LCoS calibration and optimization. PMID- 26367901 TI - Optical interconnection network for parallel access to multi-rank memory in future computing systems. AB - With the number of cores increasing, there is an emerging need for a high bandwidth low-latency interconnection network, serving core-to-memory communication. In this paper, aiming at the goal of simultaneous access to multi rank memory, we propose an optical interconnection network for core-to-memory communication. In the proposed network, the wavelength usage is delicately arranged so that cores can communicate with different ranks at the same time and broadcast for flow control can be achieved. A distributed memory controller architecture that works in a pipeline mode is also designed for efficient optical communication and transaction address processes. The scaling method and wavelength assignment for the proposed network are investigated. Compared with traditional electronic bus-based core-to-memory communication, the simulation results based on the PARSEC benchmark show that the bandwidth enhancement and latency reduction are apparent. PMID- 26367902 TI - Experimental demonstration of EON node supporting reconfigurable optical superchannel multicasting. AB - Elastic optical networks (EON) based on optical superchannel enables higher spectral flexibility, in which the network nodes should provide multiple all optical functionalities to manipulate bandwidth-variable data traffic. In this paper, we propose and demonstrate an EON node structure supporting reconfigurable optical superchannel multicasting. The node structure incorporates a shared multicasting module, which performs reconfigurable selection of target incoming/outgoing superchannels/replicas and leverages a group of nonlinear devices to satisfy multiple multicast requests. Moreover, an optical comb is utilized to efficiently provide and manage all pump resources for multicasting with potential cost reduction and phase noise inhibition. Based on the node structure, we experimentally demonstrate polarization division multiplexing (PDM) superchannel multicasting scenarios with different replica amount, input/output locations, and modulation formats. Less than 0.7 dB optical signal-to-noise ratio (OSNR) penalties are demonstrated in multiple multicasting scenarios. PMID- 26367903 TI - Aberration correction in coherence imaging microscopy using an image inverting interferometer. AB - We present an imaging method with the ability to correct even large optical phase aberrations in a purely numerical way. For this purpose, the complex coherence function in the pupil plane of the microscope objective is measured with the help of an image inverting interferometer. By means of a Fourier transform, it is possible to reconstruct the spatially incoherent object distribution. We demonstrate that aberrations symmetric to the optical axis do not impair the imaging quality of such a coherence imaging system. Furthermore, we show that it is possible to gain an almost complete correction of remaining aberrations with the help of a reference measurement. A mathematical derivation is given and experimentally verified. To demonstrate the ability of our method, randomly generated aberrations with peak-to-valley values of up to 8 lambda are corrected. PMID- 26367904 TI - Real-time phase measurement of optical vortices based on pixelated micropolarizer array. AB - The special spiral phase structure of an optical vortex leads to an intriguing study in modern singular optics. This paper proposes a real-time phase measurement method of vortex beam based on pixelated micropolarizer array (PMA). Four phase-shifting fringe images can be obtained from a single interference image, thus the vortex beam phase can be obtained in real-time. The proposed method can achieve full-field phase measurement of the vortex beam with the advantages of lower computation and vibration resistance. In the experiments, the typical phases of vortex with different topological charges are loaded on a spatial light modulator (SLM) to generate diffraction vortex beam, and the phase distribution of vortex beam is obtained in real-time, which confirm the robustness of this method. This method is of great significance in promoting the study of optical vortices. PMID- 26367905 TI - Helical tractor beam: analytical solution of Rayleigh particle dynamics. AB - We analyze particle dynamics in an optical force field generated by helical tractor beams obtained by the interference of a cylindrical beam with a topological charge and a co-propagating temporally de-phased plane wave. We show that, for standard experimental conditions, it is possible to obtain analytical solutions for the trajectories of particles in such force field by using of some approximations. These solutions show that, in contrast to other tractor beams described before, the intensity becomes a key parameter for the control of particle trajectories. Therefore, by tuning the intensity value the particle can describe helical trajectories upstream and downstream, a circular trajectory in a fixed plane, or a linear displacement in the propagation direction. The approximated analytical solutions show good agreement to the corresponding numerical solutions of the exact dynamical differential equations. PMID- 26367906 TI - Compact multi-channel surface plasmon resonance sensor for real-time multi analyte biosensing. AB - A compact multi-channel surface plasmon resonance (SPR) biosensor is demonstrated based on a tablet as the measurement platform. The SPR biosensor employs a bundle of fiber-optic SPR sensors as the multiplexed sensing elements that are illuminated by a light-emitting diode (LED) plane light source and detected by a cordless camera. The multi-channel SPR biosensor was based on optical fiber components for precise, label-free and high-throughput detection without the use of complex, specialized or fragile instrumentation that would require optical calibration. The reference and control channels compensated for the fluctuation of the LED light source and the bulk refractive index, increasing the accuracy and reliability of the biosensor. The multi-channel SPR biosensor was applied for multi-analyte biosensing of immunoglobulin G (IgG) and concanavalin A (Con A). The channels functionalized with staphylococcal protein A (SPA) and ribonuclease B (RNase B) only showed relative intensity responses to their corresponding analytes. Moreover, the multi-channel SPR sensors responded to the specific detection of IgG and Con A with an approximately linear relative intensity response to the analyte concentration. Hence, multiple analytes were simultaneously and quantitatively detected with the multi-channel SPR biosensor. This compact, cost-effective multi-channel SPR biosensor is adapted for point-of care tests, which are important in healthcare and environmental monitoring and for biomolecular interaction analysis. PMID- 26367907 TI - Plasmonic coaxial waveguide-cavity devices. AB - We theoretically investigate three-dimensional plasmonic waveguide-cavity structures, built by side-coupling stub resonators that consist of plasmonic coaxial waveguides of finite length, to a plasmonic coaxial waveguide. The resonators are terminated either in a short or an open circuit. We show that the properties of these waveguide-cavity systems can be accurately described using a single-mode scattering matrix theory. We also show that, with proper choice of their design parameters, three-dimensional plasmonic coaxial waveguide-cavity devices and two-dimensional metal-dielectric-metal devices can have nearly identical transmission spectra. Thus, three-dimensional plasmonic coaxial waveguides offer a platform for practical implementation of two-dimensional metal dielectric-metal device designs. PMID- 26367908 TI - Design of ultrafast laser-driven microactuator based on photoacoustic mechanism. AB - In this work, an ultrafast laser-driven microactuator based on the photoacoustic mechanism was proposed with large amplitude and high response frequency. The microactuator was fabricated by LIGA technology. The displacement of the microactuator could be up to 11 MUm at resonance state when the repeat frequency was around 14 kHz using a nanosecond pulse laser. Theoretical model was set up and the calculated results agree reasonably well with the experimental data. The microactuator based on the photoacoustic mechanism provides a more efficient actuation method. PMID- 26367909 TI - Rotational memory effect of a multimode fiber. AB - We demonstrate the rotational memory effect in a multimode fiber. Rotating the incident wavefront around the fiber core axis leads to a rotation of the resulting pattern of the fiber output without significant changes in the resulting speckle pattern. The rotational memory effect can be exploited for non invasive imaging or ultrafast high-resolution scanning through a multimode fiber. Our experiments demonstrate this effect over a full range of angles in two experimental configurations. PMID- 26367910 TI - All-optical background subtraction readout method for bimaterial cantilever array sensing. AB - Optical readout method plays a critical role in bimaterial cantilever array sensing system. The common optical readout methods are based on spectral plane filtering. In the paper an all-optical background subtraction readout approach inspired by total reflection and optical lever principle is presented for the bimaterial cantilever array sensing. Comparing with the spectral plane filtering methods the proposed approach eliminates digital subtraction operation by using optical total reflection instead of digital subtraction and avoids spectral filtering operation. An all-optical background subtraction directly-view infrared sensing system was developed to evaluate the approach. The infrared target can be directly acquired by the visible light CCD. The experimental results and analysis show its unique advantages. PMID- 26367911 TI - Miniature adjustable-focus endoscope with a solid electrically tunable lens. AB - The design, fabrication and characterization of a miniature adjustable-focus endoscope are reported. Such an endoscope consists of a solid tunable lens for optical power tuning, two slender piezoelectric benders for laterally moving the lens elements perpendicular to the optical axis, and an image fiber bundle for image transmission. Both optical and mechanical designs are presented in this paper. Dynamic tuning of optical powers from about 135 diopters to about 205 diopters is experimentally achieved from the solid tunable lens, which contains two freeform surfaces governed by 6-degree polynomials and optimized by ray tracing studies. Results show that there is no obvious distortion or blurring in the images obtained, and the recorded resolution of the lens reaches about 30 line pairs per mm. Three test targets located at various object distances of 20 mm, 50 mm and 150 mm are focused individually by the endoscope by applying different driving DC voltages to demonstrate its adjustable-focus capability. PMID- 26367912 TI - Large-scale fabrication of micro-lens array by novel end-fly-cutting-servo diamond machining. AB - Fast/slow tool servo (FTS/STS) diamond turning is a very promising technique for the generation of micro-lens array (MLA). However, it is still a challenge to process MLA in large scale due to certain inherent limitations of this technique. In the present study, a novel ultra-precision diamond cutting method, as the end fly-cutting-servo (EFCS) system, is adopted and investigated for large-scale generation of MLA. After a detailed discussion of the characteristic advantages for processing MLA, the optimal toolpath generation strategy for the EFCS is developed with consideration of the geometry and installation pose of the diamond tool. A typical aspheric MLA over a large area is experimentally fabricated, and the resulting form accuracy, surface micro-topography and machining efficiency are critically investigated. The result indicates that the MLA with homogeneous quality over the whole area is obtained. Besides, high machining efficiency, extremely small volume of control points for the toolpath, and optimal usage of system dynamics of the machine tool during the whole cutting can be simultaneously achieved. PMID- 26367913 TI - Color controllable polarization entanglement generation in optical fiber at telecommunication wavelengths. AB - This article proposes a polarized entangled photon source in optical fiber with low Raman noise that features the controllable generation of specific signal and idler wavelengths (colors) by varying the pump power. The novel two color source can provide needed telecom entangled photon wavelengths for applications in quantum communications, quantum computing, and quantum imaging. PMID- 26367914 TI - Photoacoustic elastic oscillation and characterization. AB - Photoacoustic imaging and sensing have been studied extensively to probe the optical absorption of biological tissue in multiple scales ranging from large organs to small molecules. However, its elastic oscillation characterization is rarely studied and has been an untapped area to be explored. In literature, photoacoustic signal induced by pulsed laser is commonly modelled as a bipolar "N shape" pulse from an optical absorber. In this paper, the photoacoustic damped oscillation is predicted and modelled by an equivalent mass-spring system by treating the optical absorber as an elastic oscillator. The photoacoustic simulation incorporating the proposed oscillation model shows better agreement with the measured signal from an elastic phantom, than conventional photoacoustic simulation model. More interestingly, the photoacoustic damping oscillation effect could potentially be a useful characterization approach to evaluate biological tissue's mechanical properties in terms of relaxation time, peak number and ratio beyond optical absorption only, which is experimentally demonstrated in this paper. PMID- 26367915 TI - Quasi-single mode laser output from a terrace structure added on a Nd(3+)-doped tellurite-glass microsphere prepared using localized laser heating. AB - A Nd(3+)-doped tellurite-glass terrace microsphere was fabricated, and its laser characteristics using free-space pumping were investigated. A localized laser heating technique was used for preparing the 29-um-diameter microsphere. The uncoated sphere exhibited many laser lines with 1.3-mW threshold. Fewer laser lines were observed after terrace formation. The terrace microsphere's lasing threshold was 0.6-2.4 mW depending on the pumping position in the terrace. These results indicate that the terrace structure can modify the modes of a microsphere laser and decrease the laser threshold due to an increase in the coupling efficiency between the cavity and free-space beam. PMID- 26367916 TI - Nonlinear standing waves on a periodic array of circular cylinders. AB - A periodic array of parallel and infinitely long dielectric circular cylinders surrounded by air can be regarded as a simple two-dimensional periodic waveguide. For linear cylinders, guided modes exist continuously below the lightline in various frequency intervals, but standing waves, which are special guided modes with a zero Bloch wavenumber, could exist above the lightline at a discrete set of frequencies. In this paper, we consider a periodic array of nonlinear circular cylinders with a Kerr nonlinearity, and show numerically that nonlinear standing waves exist continuously with the frequency and their amplitudes depend on the frequency. The amplitude-frequency relations are further investigated in a perturbation analysis. PMID- 26367917 TI - Experimental observation of multiple dispersive waves emitted by multiple mid infrared solitons in a birefringence tellurite microstuctured optical fiber. AB - We experimentally demonstrate multiple dispersive waves (DWs) emitted by multiple mid-infrared solitons in a birefringence tellurite microstuctured optical fiber (BTMOF). To the best of our knowledge, this is the first demonstration of multiple DWs in the non-silica fibers. By using a pulse of ~80 MHz and ~200 fs emitted from an optical parametric oscillator (OPO) as the pump source, DWs and solitons are investigated on the fast and slow axes of the BTMOF at the pump wavelength of ~1800 nm. With the average pump power increasing from ~200 to 450 mW, the center wavelength of the 1st DW decreases from ~956 to 890 nm, the 2nd DW from ~1039 to 997 nm, the 3rd DW from ~1101 to 1080 nm, and the 4th DW from ~1160 to 1150 nm. Meanwhile, obvious multiple soliton self-frequency shifts (SSFSs) are observed in the mid-infrared region. Furthermore, DWs and solitons at the pump wavelength of ~1400 and 2000 nm are investigated at the average pump power of ~350 mW. PMID- 26367918 TI - Free-space laser communication system with rapid acquisition based on astronomical telescopes. AB - The general structure of a free-space optical (FSO) communication system based on astronomical telescopes is proposed. The light path for astronomical observation and for communication can be easily switched. A separate camera is used as a star sensor to determine the pointing direction of the optical terminal's antenna. The new system exhibits rapid acquisition and is widely applicable in various astronomical telescope systems and wavelengths. We present a detailed analysis of the acquisition time, which can be decreased by one order of magnitude compared with traditional optical communication systems. Furthermore, we verify software algorithms and tracking accuracy. PMID- 26367919 TI - All fiber magnetic field sensor with Ferrofluid-filled tapered microstructured optical fiber interferometer. AB - An ultra-compact optical fiber magnetic field sensor based on a microstructured optical fiber (MOF) modal interference and ferrofluid (FF) has been proposed and experimentally demonstrated. The magnetic field sensor was fabricated by splicing a tapered germanium-doped index guided MOF with six big holes injected with FF to two conventional single-mode fibers. The transmission spectra of the proposed sensor under different magnetic field intensities have been measured and theoretically analyzed. Due to an efficient interaction between the magnetic nanoparticles in FF and the excited cladding mode, the magnetic field sensitivity reaches up to117.9pm/mT with a linear range from 0mT to 30mT. Moreover, the fabrication process of the proposed sensor is simple, easy and cost-effective. Therefore, it will be a promising candidate for military, aviation industry, and biomedical applications, especially, for the applications where the space is limited. PMID- 26367920 TI - Dynamic optical arbitrary waveform shaping based on cascaded optical modulators of single FBG. AB - A dynamic optical arbitrary waveform generation (O-AWG) with amplitude and phase independently controlled in optical modulators of single fiber Bragg Grating (FBG) has been proposed. This novel scheme consists of several optical modulators. In the optical modulator (O-MOD), a uniform FBG is used to filter spectral component of the input signal. The amplitude is controlled by fiber stretcher (FS) in Mach-Zehnder interference (MZI) structure through interference of two MZI arms. The phase is manipulated via the second FS in the optical modulator. This scheme is investigated by simulation. Consequently, optical pulse trains with different waveforms as well as pulse trains with nonuniform pulse intensity, pulse spacing and pulse width within each period are obtained through FSs adjustment to alter the phase shifts of signal in each O-MOD. PMID- 26367921 TI - Micro-capillary-based evanescent field biosensor for sensitive, label-free DNA detection. AB - We proposed and demonstrated a micro-capillary-based, high-sensitivity evanescent field biosensor for the cost-effective, rapid, and sensitive analysis and detection of specific DNA sequences. By functionalizing the surface of the tubing wall with ssDNA probe sequences, label-free DNA detection is achieved. The wavelength shift response of the surface-functionalized biosensors to DNA hybridization is monitored in real time. Our experiments show that the biosensor can operate at room temperature and is capable of performing label-free hybridization detection, analyte concentration measurement and nucleotide mismatch detection through a single sensing device. The sensor has many advantages, such as a simple manufacturing process, standardized production control, reliable quality, low cost and an economic demodulator. The compact nature and miniature size of the biosensing detection system makes it a good candidate for the rapid and highly sensitive detection of low-concentration analytes in micro-samples for cost-effective, real-time, and on-site analysis in the fields of life science, pharmaceutical chemistry, medical science and criminal investigation. PMID- 26367922 TI - Partial coherence and polarization of a two-mode surface-plasmon polariton field at a metallic nanoslab. AB - Rigorous electromagnetic theory is utilized to characterize the partial spatial coherence and partial polarization of a two-mode field consisting of the long range and the short-range surface-plasmon polariton at a metallic nanofilm. By employing appropriate formulations for the spectral degrees of coherence and polarization, we examine the fundamental limits for these quantities associated with such a superposition field and explore how the degrees are influenced when the media, frequency, and slab thickness are varied. It is in particular shown that coherence lengths extending from subwavelength scales up to thousands of wavelengths are possible and their physical origins are elucidated. In addition, we demonstrate that for ultra-thin films the generally highly polarized two-mode field can be partially polarized in close vicinity of the polariton excitation region. The results could benefit cross-disciplinary electro-optical applications in which near-field interactions between plasmons and nanoparticles are exploited. PMID- 26367923 TI - Nanoslit-microcavity-based narrow band absorber for sensing applications. AB - We propose an ultranarrow bandwidth perfect infrared absorber consisting of a metal periodic structured surface with nanoslits, a spacer dielectric, and a metal back plate. Its bandwidth and aborption are respectively about 8 nm and 95%. The thickness of the nanobars and the spacer, and the width of the nanoslits are primary factors determining the absorption performance. This structure not only has narrow bandwidth but also can obtain the giant electric field enhancement in the tiny volume of the nanoslits. Operated as a refractive index sensor, this structure has figure of merit as high as 25. It has potential in biomedical and sensing applications. PMID- 26367924 TI - Investigating hybridization schemes of coupled split-ring resonators by electron impacts. AB - We present a comprehensive theoretical and experimental investigation of the plasmon hybridization of coupled split-ring resonators by means of the electron energy-loss spectroscopy. Split-ring resonator is a key element in design of negative refractive index metamaterials, and has been therefore intensively studied in the literature. Here, our aim is the study of hybridization effects for higher-order non-dipolar modes, which have been not investigated beforehand. We provide a complete scheme of the multimodal distribution of the coupled and single-element split-ring resonators, with a precise attention to the hybridization of those modes according to the induced moments. Our study suggests a clear dominance of electric and magnetic dipole moments over higher-order modes in the far-field radiation spectrum. PMID- 26367925 TI - Broadband THz detection from 0.1 to 22 THz with large area field-effect transistors. AB - We report on ultrafast detection of radiation between 100 GHz and 22 THz by field effect transistors in a large area configuration. With the exception of the Reststrahlenband of GaAs, the spectral coverage of the GaAs-based detectors is more than two orders of magnitude, covering the entire THz range (100 GHz - 10 THz). The temporal resolution of the robust devices is yet limited by the 30 GHz oscilloscope used for read out. The responsivity roll-off towards higher frequencies is weaker than expected from an RC-roll-off model. Terahertz pulses with peak powers of up to 65kW have been recorded without damaging the devices. PMID- 26367926 TI - 2.3 Gbit/s underwater wireless optical communications using directly modulated 520 nm laser diode. AB - We experimentally demonstrate a record high-speed underwater wireless optical communication (UWOC) over 7 m distance using on-off keying non-return-to-zero (OOK-NRZ) modulation scheme. The communication link uses a commercial TO-9 packaged pigtailed 520 nm laser diode (LD) with 1.2 GHz bandwidth as the optical transmitter and an avalanche photodiode (APD) module as the receiver. At 2.3 Gbit/s transmission, the measured bit error rate of the received data is 2.23*10( 4), well below the forward error correction (FEC) threshold of 2*10(-3) required for error-free operation. The high bandwidth of the LD coupled with high sensitivity APD and optimized operating conditions is the key enabling factor in obtaining high bit rate transmission in our proposed system. To the best of our knowledge, this result presents the highest data rate ever achieved in UWOC systems thus far. PMID- 26367927 TI - Compact iodine-stabilized laser operating at 531 nm with stability at the 10(-12) level and using a coin-sized laser module. AB - We demonstrate a compact iodine-stabilized laser operating at 531 nm using a coin sized light source consisting of a 1062-nm distributed-feedback diode laser and a frequency-doubling element. A hyperfine transition of molecular iodine is observed using the light source with saturated absorption spectroscopy. The light source is frequency stabilized to the observed iodine transition and achieves frequency stability at the 10(-12) level. The absolute frequency of the compact laser stabilized to the a(1) hyperfine component of the R(36)32 - 0 transition is determined as 564074632419(8) kHz with a relative uncertainty of 1.4*10(-11). The iodine-stabilized laser can be used for various applications including interferometric measurements. PMID- 26367928 TI - 1024 QAM, 7-core (60 Gbit/s x 7) fiber transmission over 55 km with an aggregate potential spectral efficiency of 109 bit/s/Hz. AB - We report the first 1024 QAM polarization-multiplexed transmission at 3 Gsymbol/s over a 55 km 7-core fiber, with a total bit rate of 420 Gbit/s (60 Gbit/s x 7 cores). The potential spectral efficiency per core reached 15.6 bit/s/Hz, which corresponds to an aggregate spectral efficiency as high as 109 bit/s/Hz in a multi-core single-mode fiber. PMID- 26367929 TI - One-chip integration of optical correlator based on slow-light devices. AB - We propose and demonstrate an on-chip optical correlator, in which two types of photonic crystal slow-light waveguides are integrated and operated as an optical delay scanner and a two-photon-absorption photodetector. The footprint of the device, which was fabricated using a CMOS-compatible process, was 1.0 * 0.3 mm(2), which is substantially smaller than that of conventional optical correlators with free-space optics. We observed optical pulses using this device and confirmed the correspondence of pulse waveforms with those observed using a commercial correlator when the pulse width was 5-7 ps. This device will achieve one-chipping of an optical correlator and related measurement instruments. PMID- 26367930 TI - Two-fold transmission reach enhancement enabled by transmitter-side digital backpropagation and optical frequency comb-derived information carriers. AB - We demonstrate a two-fold reach extension of 16 GBaud 16-Quadrature Amplitude Modulation (QAM) wavelength division multiplexed (WDM) system based on erbium doped fiber amplifier (EDFA)-only amplified standard and single mode fiber -based link. The result is enabled by transmitter-side digital backpropagation and frequency referenced carriers drawn from a parametric comb. PMID- 26367931 TI - 60-nm-thick basic photonic components and Bragg gratings on the silicon-on insulator platform. AB - We demonstrate integrated basic photonic components and Bragg gratings using 60 nm-thick silicon-on-insulator strip waveguides. The ultra-thin waveguides exhibit a propagation loss of 0.61 dB/cm and a bending loss of approximately 0.015 dB/180 degrees with a 30 MUm bending radius (including two straight-bend waveguide junctions). Basic structures based on the ultra-thin waveguides, including micro ring resonators, 1 * 2 MMI couplers, and Mach-Zehnder interferometers are realized. Upon thinning-down, the waveguide effective refractive index is reduced, making the fabrication of Bragg gratings possible using the standard 248 nm deep ultra-violet (DUV) photolithography process. The Bragg grating exhibits a stopband width of 1 nm and an extinction ratio of 35 dB, which is practically applicable as an optical filter or a delay line. The transmission spectrum can be thermally tuned via an integrated resistive micro-heater formed by a heavily doped silicon slab beside the waveguide. PMID- 26367932 TI - Speckle intensity statistics for chromatic scattering media under partially polarized illumination. AB - Intensity contrast in a fully developed speckle pattern resulting from the elastic scattering of a partially polarized light from a strongly scattering medium is theoretically and numerically studied. Simple expressions are derived when the illumination bandwidth is much smaller or larger than the chromatic length of the scattering medium. PMID- 26367933 TI - Tailored fibre waveguides for precise two-axis Lissajous scanning. AB - A two-axis optical imaging system using a Lissajous scan pattern with non-integer frequency ratio is presented. A waveguide with precisely tuned mechanical resonant frequencies is constructed by dip coating two fibres with a transparent polymer. Motion is achieved by mounting a waveguide cantilever at 45 degrees on a single piezoelectric actuator with a dual-frequency drive. Confocal signal collection is achieved using a mode-stripping detector, and feedback signals needed for frequency and phase locking are derived from intermittent reflection from an apertured mirror. The first scan axis is locked to the resonance of one of the modes, while the second scan axis is locked to the correct phase at the desired frequency ratio. Accurate acquisition of two-dimensional images is demonstrated. PMID- 26367934 TI - Highly efficient tunable mid-infrared optical parametric oscillator pumped by a wavelength locked, Q-switched Er:YAG laser. AB - A highly efficient and stable mid-infrared optical parametric oscillator is demonstrated, pumped by an electro-optic Q-switched Er:YAG laser with operating wavelength locked at 1645 nm by a volume Bragg grating. The oscillator, based on MgO-doped periodically poled lithium niobate (MgO:PPLN) crystal, yields a maximum overall average output power in excess of 1 W, corresponding to a conversion efficiency of 35.5% and a slope efficiency of 43.6%. The signal and idler wavelengths of the OPO are around ~2.7 MUm and ~4.3 MUm, respectively, corresponding to the two peak absorption bands of CO(2). Lasing characteristics of the oscillator, including the time evolution of the pump, signal and idler pulses at different pump power levels, are also investigated. Temperature tuning of the MgO:PPLN crystal gives signal and idler ranges of 2.67 to 2.72 MUm and 4.17 to 4.31 MUm, respectively. PMID- 26367935 TI - Selective electric and magnetic sensitivity of aperture probes. AB - We report the effect of geometrical factors governing the polarization profiles of near-field scanning optical microscope (NSOM) probes. The most important physical parameter controlling the selective electric or magnetic field sensitivity is found to be the width of the metal rim surrounding aperture. Probes with metal rim width w < lambda/2 selectively senses the optical electric field, while those with w > lambda/2 selectively senses the optical magnetic field. Intensity variation of optical Hertz standing wave formed upon reflection at oblique incidence shows a phase difference of pi/2 between electric and magnetic probes: an analogue of the classical Wiener's experiment. Our work paves way towards electromagnetic engineering of nanostructures. PMID- 26367936 TI - Circumferential irradiation for interstitial coagulation of urethral stricture. AB - An optical diffuser was developed to achieve radially uniform light irradiation by micro-machining helical patterns on the fiber surface for endoscopically treating urethral stricture. Spatial emission from the diffuser was evaluated by goniometric measurements. A computational model was developed to predict spatio temporal heat distribution during the interstitial coagulation. The fabricated diffuser yielded circumferential light distribution with slightly concentrated energy at the proximal end. Both simulation and tissue testing demonstrated approximately 1-mm coagulation thickness at 6 W for 10 sec with 1470 nm. The proposed optical diffuser may be a feasible tool to treat the urethral stricture in a uniform manner. PMID- 26367937 TI - Light induced self-written waveguides interactions in photopolymer media. AB - We present experimental and theoretical study of the interaction of Light Induced Self-Written (LISW) waveguides in photopolymers. We show that the diffusion of the monomer controls the refractive index distribution. Consequently it influences the interaction between the LISW channels allowing the observation of anti-crossing behavior or the propagation of an array of non interacting LISW waveguides. PMID- 26367938 TI - Axial range of conjugate adaptive optics in two-photon microscopy. AB - We describe an adaptive optics technique for two-photon microscopy in which the deformable mirror used for aberration compensation is positioned in a plane conjugate to the plane of the aberration. We demonstrate in a proof-of-principle experiment that this technique yields a large field of view advantage in comparison to standard pupil-conjugate adaptive optics. Further, we show that the extended field of view in conjugate AO is maintained over a relatively large axial translation of the deformable mirror with respect to the conjugate plane. We conclude with a discussion of limitations and prospects for the conjugate AO technique in two-photon biological microscopy. PMID- 26367939 TI - Ultrafast Nyquist OTDM demultiplexing using optical Nyquist pulse sampling in an all-optical nonlinear switch. AB - We propose the ultrahigh-speed demultiplexing of Nyquist OTDM signals using an optical Nyquist pulse as both a signal and a sampling pulse in an all-optical nonlinear switch. The narrow spectral width of the Nyquist pulses means that the spectral overlap between data and control pulses is greatly reduced, and the control pulse itself can be made more tolerant to dispersion and nonlinear distortions inside the nonlinear switch. We apply the Nyquist control pulse to the 640 to 40 Gbaud demultiplexing of DPSK and DQPSK signals using a nonlinear optical loop mirror (NOLM), and demonstrate a large performance improvement compared with conventional Gaussian control pulses. We also show that the optimum spectral profile of the Nyquist control pulse depends on the walk-off property of the NOLM. PMID- 26367940 TI - Compact three-core fibers with ultra-low differential group delays for broadband mode-division multiplexing. AB - An approximate explicit condition for the achievement of zero differential group delay (DGD) in a homogeneous multicore fiber (MCF) is presented and verified numerically for a step-index three-core fiber. This condition is explored for the study of compact three-core fibers with low DGDs. To achieve an ultra-low DGD in the C-band, a three-core fiber with a central refractive-index dip in each core is proposed and analyzed in detail. A specific design with three touching cores and a core-cladding index difference of 0.3% yields a maximum DGD smaller than 3.2 ps/km in the C-band. The fiber is suitable for broadband mode-division multiplexing applications and the design approach could be applied to MCFs with more cores. PMID- 26367941 TI - Generating orthogonally circular polarized states embedded in nonplanar geometric beams. AB - We experimentally demonstrated the generation of orthogonally circular polarized states embedded in nonplanar geometric beams. Experimental results revealed that the production of circularly polarized beams, induced by crystal birefringence, is quantized. Numerical analyses of the polarization and the spatial morphology are consistent with the experimental results. PMID- 26367942 TI - Silicon-chip source of bright photon pairs. AB - Integrated quantum photonics relies critically on the purity, scalability, integrability, and flexibility of a photon source to support diverse quantum functionalities on a single chip. Here we report a chip-scale photon-pair source on the silicon-on-insulator platform that utilizes dramatic cavity-enhanced four wave mixing in a high-Q silicon microdisk resonator. The device is able to produce high-quality photon pairs at different wavelengths with a high spectral brightness of 6.24*10(7) pairs/s/mW(2)/GHz and photon-pair correlation with a coincidence-to-accidental ratio of 1386 +/- 278 while pumped with a continuous wave laser. The superior performance, together with the structural compactness and CMOS compatibility, opens up a great avenue towards quantum silicon photonics with capability of multi-channel parallel information processing for both integrated quantum computing and long-haul quantum communication. PMID- 26367943 TI - Moire fringe alignment using composite circular-line gratings for proximity lithography. AB - We explore the feasibility of a controllable and easy-to-implement moire-based composite circular-line gratings imaging scheme for optical alignment in proximity lithography. One circular grating and four line gratings located on both the mask alignment mark and wafer alignment mark are used to realize the coarse alignment and fine alignment respectively. The fundamental derivation of coarse alignment employing circular gratings and fine alignment employing line gratings are given. Any displacement of misalignment that occurs at the surface of two overlapped gratings can be sensed and determined through subsequent fringe phase analysis without the influence of the gap between the mask and the wafer or wafer process. The design and manufacture process of the alignment marks are presented. The experimental results validate and demonstrate the feasibility of the proposed approach. PMID- 26367944 TI - High-resolution digital holography with the aid of coherent diffraction imaging. AB - The image reconstructed in ordinary digital holography was unable to bring out desired resolution in comparison to photographic materials; thus making it less preferable for many interesting applications. A method is proposed to enhance the resolution of digital holography in all directions by placing a random phase plate between the specimen and the electronic camera and then using an iterative approach to do the reconstruction. With this method, the resolution is improved remarkably in comparison to ordinary digital holography. Theoretical analysis is supported by numerical simulation. The feasibility of the method is also studied experimentally. PMID- 26367945 TI - New modes in label-free super resolution based on photo-modulated reflectivity. AB - The recent advances in far-field super-resolution (SR) microscopy rely on, and therefore are limited by the ability to control the fluorescence of label molecules. We demonstrated a far field label-free SR methodology that relies on the nonlinear response of the reflectance to photo-modulation by a pump laser. Here we extend our approach in two directions. We show that the method can be further simplified and improved by using a single beam rather than a pump and probe or by adding spatial probe modulation to improve resolution. Additionally, we demonstrate SR in sectioning and further investigate the dynamics of non linearity in photo-modulated reflectance. These new modalities of nonlinear photo modulated reflectivity (NPMR) enhance its applicability using lower orders of nonlinear response. PMID- 26367946 TI - Ultrafast ellipsometric pump-probe diagnostic of liquid metal surface with chirped continuum probe pulses. AB - We describe our ellipsometric pump-probe experiment to study materials at extreme conditions. To demonstrate the performance, liquid bismuth surface is pumped by intense 25 fs pulse and subsequent evolution of non-equilibrium bismuth plasma is probed by chirped continuum pulse. The shift in the origin-time at continuum spectral component is precisely corrected by comparing chirp behavior estimated from induced phase modulation (IPM) in fused silica to one from liquid bismuth reflectivity measurement. From IPM measurements, it was found that the time resolution of a chirped pulse depends on group delay dispersion at corresponding continuum spectral components. Moreover, due to explicit relation between time and frequency of a chirped probe pulse, pump induced rapid changes are projected onto different probe wavelengths. Using these properties, we investigated polarization dependent reflection dynamics of non-equilibrium bismuth plasma with sub-100 fs temporal resolution and a broader wavelength response. These ultrafast measurements will be useful to study exotic phase transitions at extreme states of matter. PMID- 26367947 TI - Sparse synthetic aperture with Fresnel elements (S-SAFE) using digital incoherent holograms. AB - Creating a large-scale synthetic aperture makes it possible to break the resolution boundaries dictated by the wave nature of light of common optical systems. However, their implementation is challenging, since the generation of a large size continuous mosaic synthetic aperture composed of many patterns is complicated in terms of both phase matching and time-multiplexing duration. In this study we present an advanced configuration for an incoherent holographic imaging system with super resolution qualities that creates a partial synthetic aperture. The new system, termed sparse synthetic aperture with Fresnel elements (S-SAFE), enables significantly decreasing the number of the recorded elements, and it is free from positional constrains on their location. Additionally, in order to obtain the best image quality we propose an optimal mosaicking structure derived on the basis of physical and numerical considerations, and introduce three reconstruction approaches which are compared and discussed. The super resolution capabilities of the proposed scheme and its limitations are analyzed, numerically simulated and experimentally demonstrated. PMID- 26367948 TI - Broadband asymmetric light transmission via all-dielectric digital metasurfaces. AB - We demonstrate broadband asymmetric transmission or optical-diode behavior via a digital metasurface, that is, a surface that is digitally patterned at subwavelength dimensions. Enhanced light-matter interactions at the interfaces of the metasurface break the symmetry in the propagation direction, and enables high light-transmission in one direction, while strongly reflecting the light in the opposite direction. We measured a peak extinction ratio of 11.18 dB and peak forward transmission efficiency of 74.3% at the design wavelength of 1.55MUm. The operational bandwidth of the device was 201nm. We further designed, fabricated and experimentally characterized a digital metasurface that enables polarization independent optical-diode behavior, which we believe is the first device of its kind. Our digital metasurfaces enable the optical-diode behavior in a single layer of sub-wavelength thickness for several input modes and therefore, can perform as a passive, albeit imperfect optical isolator. PMID- 26367949 TI - Evanescently coupled optical fiber refractometer based a tilted fiber Bragg grating and a D-shaped fiber. AB - A novel tip-reflective and power-referenced refractometer based on strong fiber to-fiber optical coupling for a large range of surrounding refractive index (SRI) (from 1.33 to 1.45) is proposed and experimentally demonstrated. A short D-shaped fiber stub is placed in parallel and close contact to another standard circular fiber containing a weakly tilted Bragg grating (TFBG). The TFBG couples the light from the circular fiber's core into its cladding where it remains guided. Apart from the direct light coupling over the contact interface, the evanescent field from the guided cladding modes penetrates the surroundings and reaches the D fiber core by tunneling across the medium into which the fiber pair is located. The amount of tunneling depends strongly on the SRI so that the total amount of light collected by the D-fiber provides a measure of the SRI. Sensitivities ranging from ~1000 to 13000 nW/RIU (Refractive Index Unit) have been obtained and the result is independent of temperature (within +/-10 nW of uncertainty). The measurement can be temperature-referenced through measurement of the TFBG spectrum if needed. PMID- 26367950 TI - Soft mold-based hot embossing process for precision imprinting of optical components on non-planar surfaces. AB - Patterning micro- and nano-scale optical elements on nonplanar substrates has been technically challenging and prohibitively expensive via conventional processes. A low-cost, high-precision fabrication process is thus highly desired and can have significant impact on manufacturing that leads to wider applications. In this paper, we present a new hot embossing process that enables high-resolution patterning of micro- and nano-structures on non-planar substrates. In this process, a flexible elastomer stamp, i.e., PDMS, was used as a mold to perform hot-embossing on substrates of arbitrary curvatures. The new process was optimized through the development of an automated vacuum thermal imprinting system that allows non-clean room operation as well as precise control of all process parameters, e.g., pressure, temperature and time. Surface profiles and optical properties of the fabricated components, including micro-lens array and optical gratings, were characterized quantitatively, e.g., RMS ~lambda/30 for a micro-lens, and proved to be comparable with high cost conventional precision processes such as laser lithographic fabrication. PMID- 26367951 TI - Modeling of pulsed K diode pumped alkali laser: Analysis of the experimental results. AB - A simple optical model of K DPAL, where Gaussian spatial shapes of the pump and laser intensities in any cross section of the beams are assumed, is reported. The model, applied to the recently reported highly efficient static, pulsed K DPAL [Zhdanov et al, Optics Express 22, 17266 (2014)], shows good agreement between the calculated and measured dependence of the laser power on the incident pump power. In particular, the model reproduces the observed threshold pump power, 22 W (corresponding to pump intensity of 4 kW/cm2), which is much higher than that predicted by the standard semi-analytical models of the DPAL. The reason for the large values of the threshold power is that the volume occupied by the excited K atoms contributing to the spontaneous emission is much larger than the volumes of the pump and laser beams in the laser cell, resulting in very large energy losses due to the spontaneous emission. To reduce the adverse effect of the high threshold power, high pump power is needed, and therefore gas flow with high gas velocity to avoid heating the gas has to be applied. Thus, for obtaining high power, highly efficient K DPAL, subsonic or supersonic flowing-gas device is needed. PMID- 26367952 TI - Non-line-of-sight imaging using a time-gated single photon avalanche diode. AB - By using time-of-flight information encoded in multiply scattered light, it is possible to reconstruct images of objects hidden from the camera's direct line of sight. Here, we present a non-line-of-sight imaging system that uses a single pixel, single-photon avalanche diode (SPAD) to collect time-of-flight information. Compared to earlier systems, this modification provides significant improvements in terms of power requirements, form factor, cost, and reconstruction time, while maintaining a comparable time resolution. The potential for further size and cost reduction of this technology make this system a good base for developing a practical system that can be used in real world applications. PMID- 26367953 TI - Nanophotonic projection system. AB - Low-power integrated projection technology can play a key role in development of low-cost mobile devices with built-in high-resolution projectors. Low-cost 3D imaging and holography systems are also among applications of such a technology. In this paper, an integrated projection system based on a two-dimensional optical phased array with fast beam steering capability is reported. Forward biased p-i-n phase modulators with 200MHz bandwidth are used per each array element for rapid phase control. An optimization algorithm is implemented to compensate for the phase dependent attenuation of the p-i-n modulators. Using rapid vector scanning technique, images were formed and recorded within a single snapshot of the IR camera. PMID- 26367954 TI - Wide-angle and polarization independent perfect absorber based on one-dimensional fabrication-tolerant stacked array. AB - We propose a wide-angle, polarization independent and fabrication-tolerant perfect absorber, which is based on a one-dimensional stacked array consisted of vertically cascaded two pairs of metal-dielectric bilayers. The results show that the absorption peaks are over 99% at the wavelength of 5.25 MUm for different polarization angles, and remain very high within wide ranges of incident and azimuthal angles. We attribute those excellent performances to the excitation of the magnetic resonance (MR) and the guided mode resonance (GMR) for the TM and TE polarization, respectively, and are further expounded by the inductor-capacitor (LC) circuit model and the eigen equation of the GMR, respectively. More importantly, this one-dimensional absorber is very robust to the spacing distance between the neighboring stacks and the metallic strip thickness, which releases degrees of freedom in design and makes the absorber extremely flexible and simple in fabrication, thus it can be a good candidate for many fascinating applications. PMID- 26367955 TI - Graphene-based perfect optical absorbers harnessing guided mode resonances. AB - We investigate graphene-based optical absorbers that exploit guided mode resonances (GMRs) attaining theoretically perfect absorption over a bandwidth of few nanometers (over the visible and near-infrared ranges) with a 40-fold increase of the monolayer graphene absorption. We analyze the influence of the geometrical parameters on the absorption rate and the angular response for oblique incidence. Finally, we experimentally verify the theoretical predictions in a one-dimensional, dielectric grating by placing it near either a metallic or a dielectric mirror, thus achieving very good agreement between numerical predictions and experimental results. PMID- 26367956 TI - In vivo tear film thickness measurement and tear film dynamics visualization using spectral domain optical coherence tomography. AB - Dry eye syndrome is a highly prevalent disease of the ocular surface characterized by an instability of the tear film. Traditional methods used for the evaluation of tear film stability are invasive or show limited repeatability. Here we propose a new non-invasive fully automated approach to measure tear film thickness based on spectral domain optical coherence tomography and on an efficient delay estimator. Silicon wafer phantom were used to validate the thickness measurement. The technique was applied in vivo in healthy subjects. Series of tear film thickness maps were generated, allowing for the visualization of tear film dynamics. Our results show that the in vivo central tear film thickness measurements are precise and repeatable with a coefficient of variation of about 0.65% and that repeatable tear film dynamics can be observed. The presented approach could be used in clinical setting to study patients with dry eye disease and monitor their treatments. PMID- 26367957 TI - Ultrafast thin-disk multipass laser amplifier delivering 1.4 kW (4.7 mJ, 1030 nm) average power converted to 820 W at 515 nm and 234 W at 343 nm. AB - We report on an Yb:YAG thin-disk multipass laser amplifier delivering sub-8 ps pulses at a wavelength of 1030 nm with 1420 W of average output power and 4.7 mJ of pulse energy. The amplifier is seeded by a regenerative amplifier delivering 6.5 ps pulses with 300 kHz of repetition rate and an average power of 115 W. The optical efficiency of the multipass amplifier was measured to be 48% and the beam quality factor was better than M2 = 1.4. Furthermore we report on the external second harmonic generation from 1030 nm to 515 nm using an LBO crystal leading to an output power of 820 W with 2.7 mJ of energy per pulse. This corresponds to a conversion efficiency of 70%. Additionally, 234 W of average power were obtained at the third harmonic with a wavelength of 343 nm. PMID- 26367958 TI - Multifrequency swept common-path en-face OCT for wide-field measurement of interior surface vibrations in thick biological tissues. AB - Microvibrations that occur in bio-tissues are considered to play pivotal roles in organ function; however techniques for their measurement have remained underdeveloped. To address this issue, in the present study we have developed a novel optical coherence tomography (OCT) method that utilizes multifrequency swept interferometry. The OCT volume data can be acquired by sweeping the multifrequency modes produced by combining a tunable Fabry-Perot filter and an 840 nm super-luminescent diode with a bandwidth of 160 nm. The system employing the wide-field heterodyne method does not require mechanical scanning probes, which are usually incorporated in conventional Doppler OCTs and heterodyne-type interferometers. These arrangements allow obtaining not only 3D tomographic images but also various vibration parameters such as spatial amplitude, phase, and frequency, with high temporal and transverse resolutions over a wide field. Indeed, our OCT achieved the axial resolution of ~2.5 MUm when scanning the surface of a glass plate. Moreover, when examining a mechanically resonant multilayered bio-tissue in full-field configuration, we captured 22 nm vibrations of its internal surfaces at 1 kHz by reconstructing temporal phase variations. This so-called "multifrequency swept common-path en-face OCT" can be applied for measuring microdynamics of a variety of biological samples, thus contributing to the progress in life sciences research. PMID- 26367959 TI - Surface relief apodized grating tunable filters produced by using a shadow mask. AB - To produce a compact low-cost tunable filter required for WDM optical communications, a polymeric Bragg reflection filter with an apodized grating structure is proposed. A high-contrast polymeric waveguide is incorporated in order to obtain high reflectivity from a short Bragg grating. To overcome the bandwidth broadening, an apodized grating with a gradually changing depth of surface relief grating along the propagation direction is fabricated through the dry etching with a shadow mask. The apodized polymer grating exhibits 3-dB, 20-dB bandwidths of 0.36 nm, and 0.72 nm, respectively with a 95% reflection. The reflection wavelength is tunable over 14 nm for an applied thermal power of 500 mW. PMID- 26367960 TI - Enhanced graphene absorption and linewidth sharpening enabled by Fano-like geometric resonance at near-infrared wavelengths. AB - We theoretically investigate the light-graphene interactions enabled by a single layer of nonlossy nanorods at near-infrared wavelengths. The sustained Fano-like geometric resonance gives rise to enhanced graphene absorption, e.g., 100%, and adjustable absorption linewidth even to be ultra-narrow, e.g., < 1 nm. The conditions for such graphene absorption enhancement and linewidth sharpening are analytically interpreted within the framework of temporal coupled mode theory for the Fano resonance. The geometric resonance enhanced light-graphene interactions are polarization-sensitive and angle-dependent. Our study offers new possibilities towards designing and fabricating novel opto-electronic devices such as graphene-integrated monochromatic photodetectors and ultra-compact modulators. PMID- 26367961 TI - Measurement of sub-10 fs Auger processes in monolayer graphene. AB - Despite the concerted efforts to directly probe the electron-electron (e-e) scattering mediated relaxation process in graphene using transient absorption spectroscopy, the initial sub-10 fs photoexcited carrier relaxation dynamics has remained elusive. Herein, we utilize a simple z-scan approach to elucidate this process and discern its mechanisms in CVD grown single layer graphene using femtosecond laser pulses with temporal pulse widths far longer than the relaxation time. We report the first experimental observation of e-e scattering lifetime shortening with increasing fluence, which had been theoretically predicted. Analysis from two-body Coulombic scattering suggests that Auger processes are essential relaxation channels in single layer graphene. Importantly, our straightforward approach on the graphene model system is applicable to the family of emergent layered materials. PMID- 26367962 TI - Spectroscopy and laser operation of Sm(3+)-doped lithium lutetium tetrafluoride (LiLuF(4)) and strontium hexaaluminate (SrAl(12)O(19)). AB - We report on laser operation in the orange and red spectral range in samarium (Sm(3+))-doped fluoride and oxide crystals at 300 K. Sm(3+)-doped LiLuF(4) (LLF) and SrAl(12)O(19) (SRA) crystals were grown by the Czochralski-technique and utilized for spectroscopic investigations and laser experiments. The spin forbidden transitions of Sm(3+)exhibit low cross sections the order of 10(-21) cm(2), but high radiative upper state lifetimes of several ms in both crystal systems. Under 2omega-OPSL-pumping at 480 nm, orange laser operation was achieved with Sm:LLF and Sm,Mg:SRA at lasing wavelengths of 606 nm and 593 nm, respectively. Furthermore laser oscillation was demonstrated at 648 nm in the red and 703 nm in the deep red spectral range with Sm:LLF and Sm,Mg:SRA, respectively. Output power levels of several 10 mW were obtained at slope efficiencies of up to 15 %. Most of the realized lasers were operating in a strongly modulated or even self-pulsing regime. PMID- 26367963 TI - Anisotropic materials in OLEDs for high outcoupling efficiency. AB - We present the results of an optical study in which we evaluate the effect of anisotropic electron transport layers (ETL) and anisotropic hole transport layers (HTL) on the outcoupling efficiency of bottom emitting organic light emitting diodes (OLEDs). We demonstrate that optical anisotropy can have a profound influence on the outcoupling efficiency and introduce a number of design rules which ensure that light extraction is enhanced by anisotropic layers. PMID- 26367964 TI - Dual electro-optic optical frequency combs for multiheterodyne molecular dispersion spectroscopy. AB - In this paper, a multiheterodyne architecture for molecular dispersion spectroscopy based on a coherent dual-comb source generated using a single continuous wave laser and electro-optic modulators is presented and validated. The phase-sensitive scheme greatly simplifies previous dual-comb implementations by the use of an electro-optic dual comb and by phase-locking all the signal generators of the setup eliminating, in this way, the necessity of any reference optical path currently mandatory in absorption-based instruments. The architecture is immune to the classical baseline and normalization problems of absorption-based analyzers and provides an output linearly dependent on the gas concentration. In addition, the simultaneous parallel multi-wavelength measurement approach has the ability to deliver an improved output bandwidth (measurement speed) over gas analyzers based on tunable lasers. PMID- 26367965 TI - Ultra-broadband quantum cascade laser, tunable over 760 cm(-1), with balanced gain. AB - A heterogeneous quantum cascade laser, consisting of multiple stacks of discrete wavelength quantum cascade stages, emitting in 5.9-10.9 um, wavelength range is reported. The broadband characteristics are demonstrated with a distributed feedback laser array, emitting at fixed frequencies at room temperature, covering an emission range of ~760 cm(-1), which is ~59% relative to the center frequency. By appropriate choice of a strained AlInAs/GaInAs material system, quantum cascade stage design and spatial arrangement of stages, the distributed-feedback array has been engineered to exhibit a flat threshold current density across the demonstrated range. PMID- 26367966 TI - Hybrid transmission bands and large birefringence in hollow-core anti-resonant fibers. AB - We identify, for the first time to our best knowledge, a new type of transmission band having hybrid resonance nature in hollow-core anti-resonant fibers (ARF). We elucidate its unique phase-locking feature of the electric field at the outermost boundary. Exploiting this hybrid band, large birefringence in the order of 10(-4) is obtained. Our analyses based on Kramer-Kronig relation and transverse field confinement interpret the link between the hybrid transmission band and the large birefringence. Guided by these analyses, an experimentally realizable polarization-maintaining ARF design is proposed by introducing multi-layered dielectric structure into a negative curvature core-surround. This multi-layered ARF possesses characteristics of low loss, broad transmission band and large birefringence simultaneously. PMID- 26367967 TI - Quasi-distributed and wavelength selective addressing of optical micro-resonators based on long period fiber gratings. AB - A novel all-in-fiber method for coupling light to high-Q silica whispering gallery mode (WGM) optical micro-resonators is presented, which is based on a pair of long period fiber gratings (LPGs) written in the same silica fiber, along with a thick fiber taper (15-18 MUm in waist) in between the LPGs. The proposed coupling structure is robust and can be replicated many times along the same fiber simply cascading LPGs with different bands. Typical Q-factors of the order of 10(8) and total coupling efficiency up to 60% were measured collecting the resonances of microspheres or microbubbles at the fiber end. This approach uniquely allows quasi-distributed and wavelength selective addressing of different micro-resonators along the same fiber. PMID- 26367968 TI - Robust terahertz self-heterodyne system using a phase noise compensation technique. AB - We propose and demonstrate a robust terahertz self-heterodyne system using a phase noise compensation technique. Conventional terahertz self-heterodyne systems suffer from degraded phase noise performance due to phase noise of the laser sources. The proposed phase noise compensation technique uses an additional photodiode and a simple electric circuit to produce phase noise identical to that observed in the terahertz signal produced by the self-heterodyne system. The phase noise is subsequently subtracted from the terahertz signal produced by the self-heterodyne system using a lock-in amplifier. While the terahertz self heterodyne system using a phase noise compensation technique offers improved phase noise performance, it also provides a reduced phase drift against ambient temperature variations. The terahertz self-heterodyne system using a phase noise compensation technique shows a phase noise of 0.67 degree in terms of a standard deviation value even without using overall delay balance control. It also shows a phase drift of as small as approximately 10 degrees in an open-to-air measurement condition without any strict temperature control. PMID- 26367969 TI - Tripartite counterfactual entanglement distribution. AB - We propose two counterfactual schemes for tripartite entanglement distribution without any physical particles travelling through the quantum channel. One scheme arranges three participators to connect with the absorption object by using switch. Using the "chained" quantum Zeno effect, three participators can accomplish the task of entanglement distribution with unique counterfactual interference probability. Another scheme uses Michelson-type interferometer to swap two entanglement pairs such that the photons of three participators are entangled. Moreover, the distance of entanglement distribution is doubled as two distant absorption objects are used. We also discuss the implementation issues to show that the proposed schemes can be realized with current technology. PMID- 26367970 TI - Enhanced photo-response properties of a single ZnO microwire photodetector by coupling effect between localized Schottky barriers and piezoelectric potential. AB - The coupling effect between localized Schottky barriers (SBs) and piezoelectric potential that impact the photo-response properties of a single ZnO microwire (MW) photodetector (PD) is studied. Localized SBs is introduced by Au NPs decoration. The negatively charged Au NPs deplete more carriers near the ZnO surface, which raises the SB height and sharply reduces the recover time of the PD from 142.4 s to 0.7 s. Moreover, after applying the compressive strain, the band structure of ZnO MW changes and piezoelectric potential generates, which further raises the SB height, thickens the depletion region and improves photo response properties of the detector. The dark current is reduced by about 5 orders and its on/off current ratio increased by about 6 orders, which decreases the power consumption of the detector significantly. Under the above coupling effect between piezoelectric potential and localized SBs, the recover time of the detector is further reduced to 0.1 s ultimately. This work suggests that rational integration of localized SBs and piezoelectric potential is a viable approach to get ZnO MW PDs with high on/off ratio, ultrafast response speed and low power consumption. PMID- 26367971 TI - Acoustically driven arrayed waveguide grating. AB - We demonstrate compact tunable phased-array wavelength-division multiplexers driven by surface acoustic waves (SAWs) in the low GHz range. The devices comprise two couplers, which respectively split and combine the optical signal, linked by an array of single-mode waveguides (WGs). Two different layouts are presented, in which multi-mode interference couplers or free propagating regions were separately employed as couplers. The multiplexers operate on five equally distributed wavelength channels, with a spectral separation of 2 nm. A standing SAW modulates the refractive index of the arrayed WGs. Each wavelength component periodically switches paths between the output channel previously asigned by the design and the adjacent channels, at a fixed applied acoustic power. The devices were monolithically fabricated on (Al,Ga)As. A good agreement between theory and experiment is achieved. PMID- 26367972 TI - Robust calibration method for pure rotational Raman lidar temperature measurement. AB - A new calibration method for pure rotational Raman lidar temperature measurement is described in this work. The method forms a temperature-dependent term in the intensity ratio, which is calculable with the radiosonde data, and then derives a calibration factor, with which the temperature is retrievable from the lidar return. The method is demonstrated and compared with existing methods through simulations and experiments. Results of the comparison show that the proposed method could provide more accurate calibrations under low signal-to-noise ratio conditions and could thus reduce the lidar performance requirement for temperature retrieval. PMID- 26367973 TI - Firsthand in situ observation of active fine laser tuning by combining a temperature gradient and a CLC wedge cell structure. AB - In situ direct observation of the lasing process in a cholesteric liquid crystal (CLC) laser array using a CMOS camera was used to investigate discontinuous laser tuning in a parallel CLC cell. In accordance with the discontinuous pitch change by thermal energy transfer, at the same time the laser wavelength undergoes an immediate and discontinuous shift. And we found out the reason why the CLC phase has domain textures. And this work develops a simple active tunable laser array by forming a spatial temperature gradient along a wedge CLC cell. With this new strategy, only just about 7 nm laser tuning range at room temperature is extremely widened over the 105 nm wavelength range with about 0.2 nm tuning resolution. Furthermore, there is no aging effect because the employed CLC array has only one chiral molecular concentration. This strategy could be used in a practical CLC laser device application. PMID- 26367974 TI - Radial-firing optical fiber tip containing conical-shaped air-pocket for biomedical applications. AB - We report a novel radial-firing optical fiber tip containing a conical-shaped air pocket fabricated by deforming a hollow optical fiber using electric arc discharge process. The hollow optical fiber was fusion spliced with a conventional optical fiber, simultaneously deforming into the intagliated conical shaped region along the longitudinal fiber-axis of the fiber due to the gradual collapse of the cavity of the hollow optical fiber. Then the distal-end of the hollow optical fiber was sealed by the additional arc-discharge in order to obstruct the inflow of an external bio-substance or liquid to the inner air surface during the surgical operations, resulting in the formation of encased air pocket in the silica glass fiber. Due to the total internal reflection of the laser beam at the conical-shaped air surface, the laser beam (lambda = 632.8 nm) was deflected to the circumferential direction up to 87 degree with respect to the fiber-axis. PMID- 26367975 TI - Spherical aberration free liquid-filled tunable lens with variable thickness membrane. AB - We present an iterative design method for liquid-tunable aspherical lenses capable of diffraction-limited performance over a wide focal length range. The lenses are formed by a thin elastomer meniscus with a variable thickness profile engineered to deform into an ideal asphere under uniform pressure load. Compared to their more conventional counterparts, the proposed lenses significantly reduce spherical aberration over a larger portion of the aperture. The design procedure begins with the semi-analytical calculation of the meniscus thickness profile using large-deflection thin plate theory. This initial profile is then further optimized using coupled finite element analysis and ray-tracing simulations iteratively. We apply the developed method to design a tunable aspherical lens with 3 mm clear aperture and 8 mm optimum focal length, and numerically demonstrate the improvement in optical performance over conventional tunable lenses over a focal length range from 6 mm to 12 mm. Using 80% of the clear aperture, the lens has better than lambda/4 RMS surface error over the focal length range from 7.7 mm to 8.5 mm, corresponding to 10% tuning of focal length with diffraction-limited performance. The sources of potential fabrication errors in a practical implementation of such a lens are also analyzed in detail in terms of their influence on optical performance. PMID- 26367976 TI - Strong optical modulation of surface plasmon polaritons in metal/semiconductor nanostructures. AB - We demonstrate strong modulation of the transmission around the surface plasmon polariton (SPP) resonance in metal/semiconductor hybrid nanostructures based on Ag film on top of InGaAs. The change in the real and imaginary parts of the refractive index due to photoexcited carriers in InGaAs generates a shift in the SPP resonance and enhanced transmission near the SPP resonance. Temporal evolution of the complex refractive index was traced by comparing the transient transmission with finite-difference time-domain (FDTD) simulations. PMID- 26367977 TI - Spot-size converter with a SiO(2) spacer layer between tapered Si and SiON waveguides for fiber-to-chip coupling. AB - We experimentally demonstrate low-loss and polarization-insensitive fiber-to-chip coupling spot-size converters (SSCs) comprised of a three dimensionally tapered Si wire waveguide, a SiON secondary waveguide, and a SiO(2) spacer inserted between them. Fabricated SSCs with the SiO(2) spacer exhibit fiber-to-chip coupling loss of 1.5 dB/facet for both the quasi-TE and TM modes and a small wavelength dependence in the C- and L-band regions. The SiON secondary waveguide is present only around the SSC region, which significantly suppresses the influence of the well-known N-H absorption of plasma-deposited SiON at around 1510 nm. PMID- 26367978 TI - Achievement and steering of light-induced sub-wavelength longitudinal magnetization chain. AB - The light-induced magnetization distributions for a high numerical aperture focusing configuration with an azimuthally polarized Bessel-Gaussian beam modulated by optimized vortex binary filters are investigated based on the inverse Faraday effect. It is found that, by adjusting the radii of different rings of the single/ cascaded vortex binary filters, super-long (12lambda) and sub-wavelength (0.416lambda) longitudinal magnetization chain with single/dual channels can be achieved in the focal region. Such well-behaved magnetization trait is attributed to the mutual effect between the optical polarization singularities of the azimuthally polarized beam and single/cascaded spiral optical elements. In addition, we find that the displacement distance of the longitudinal magnetization chain is proportional to the phase difference between the inner circle and outer ring of the vortex binary filters, thus giving rise to the steerable magnetization chain. It is expected that the research outcomes can be applied in multiple atoms trapping and transport, multilayer magneto-optical data storage, fabrication of magnetic lattices for spin wave operation and development of ultra-compact optomagnetic devices. PMID- 26367979 TI - Entanglement and Einstein-Podolsky-Rosen steering between a nanomechanical resonator and a cavity coupled with two quantum dots. AB - We propose a scheme for generation of the stationary continuous-variable entanglement and Einstein-Podolsky-Rosen (EPR) steering between an optical cavity mode and a nanomechanical resonator (NMR) mode. The cavity and the NMR are commonly coupled with two separated quantum dots (QDs), where the two QDs are driven simultaneously by a strong laser field. By adjusting the frequency of the strong laser field, the two QDs are nearly trapped on different dressed states, which is helpful to generate the entanglement between the cavity mode and the NMR mode. Due to the combined resonant interaction of the two QDs with the NMR-cavity subsystem, the photon and the phonon created and (or) annihilated are correlated. In this regime, the optimal entanglement of the two modes is obtained and the purity of the state of the NMR-cavity subsystem is near to 1. Furthermore, the coupling strength between the cavity and two QDs is different from the dot-NMR coupling strength, which leads to the different mean occupation numbers of the cavity and the NMR. In this case, one-way EPR steering is observed. In addition, through analyzing the purity, we find the conditions of the existence for the different types of EPR steering. PMID- 26367980 TI - Scheme for efficient extraction of low-frequency signal beyond the quantum limit by frequency-shift detection. AB - Low-frequency (Hz~kHz) squeezing is very important in many schemes of quantum precision measurement. But it is more difficult than that at megahertz-frequency because of the introduction of laser low-frequency technical noise. In this paper, we propose a scheme to obtain a low-frequency signal beyond the quantum limit from the frequency comb in a non-degenerate frequency and degenerate polarization optical parametric amplifier (NOPA) operating below threshold with type I phase matching by frequency-shift detection. Low-frequency squeezing immune to laser technical noise is obtained by a detection system with a local beam of two-frequency intense laser. Furthermore, the low-frequency squeezing can be used for phase measurement in Mach-Zehnder interferometer, and the signal-to noise ratio (SNR) can be enhanced greatly. PMID- 26367981 TI - Low-loss compact multilayer silicon nitride platform for 3D photonic integrated circuits. AB - We design, fabricate, and demonstrate a silicon nitride (Si(3)N(4)) multilayer platform optimized for low-loss and compact multilayer photonic integrated circuits. The designed platform, with 200 nm thick waveguide core and 700 nm interlayer gap, is compatible for active thermal tuning and applicable to realizing compact photonic devices such as arrayed waveguide gratings (AWGs). We achieve ultra-low loss vertical couplers with 0.01 dB coupling loss, multilayer crossing loss of 0.167 dB at 90 degrees crossing angle, 50 MUm bending radius, 100 * 2 MUm(2) footprint, lateral misalignment tolerance up to 400 nm, and less than -52 dB interlayer crosstalk at 1550 nm wavelength. Based on the designed platform, we demonstrate a 27 * 32 * 2 multilayer star coupler. PMID- 26367982 TI - Experimental realization of hyperbolic dispersion metamaterial for the whole visible spectrum based on liquid crystalline phase soft template. AB - We experimentally demonstrated a metamaterial composed of hexagonal arrays of silver nanowires that exhibits hyperbolic dispersion and negative refraction in the entire visual wavelength range. The nanowires with extremely small size of 10 nm diameter and 15 nm center-to-center distance were fabricated using the reverse hexagonal liquid crystalline phase template containing AgNO(3) solution. Through the experiments of angle dependent reflectance for s-polarization and p polarization, the dielectric constants were measured in several wavelengths. Calculations and experiments both show hyperbolic dispersion relations from 370 nm to 750 nm which indicates the presence of all-angle negative refraction. For all the experimental wavelengths, the permittivities of the material are in good agreement with the theoretical calculations. PMID- 26367983 TI - Improved quantitative phase imaging in lensless microscopy by single-shot multi wavelength illumination using a fast convergence algorithm. AB - We report on a novel algorithm for high-resolution quantitative phase imaging in a new concept of lensless holographic microscope based on single-shot multi wavelength illumination. This new microscope layout, reported by Noom et al. along the past year and named by us as MISHELF (initials incoming from Multi Illumination Single-Holographic-Exposure Lensless Fresnel) microscopy, rises from the simultaneous illumination and recording of multiple diffraction patterns in the Fresnel domain. In combination with a novel and fast iterative phase retrieval algorithm, MISHELF microscopy is capable of high-resolution (micron range) phase-retrieved (twin image elimination) biological imaging of dynamic events. In this contribution, MISHELF microscopy is demonstrated through qualitative concept description, algorithm implementation, and experimental validation using both a synthetic object (resolution test target) and a biological sample (swine sperm sample) for the case of three (RGB) illumination wavelengths. The proposed method becomes in an alternative instrument improving the capabilities of existing lensless microscopes. PMID- 26367984 TI - Optical 8QAM and 8PSK synthesis by cascading arbitrary 2QAM with squared QPSK. AB - In dynamic optical networking scenarios, it is desirable that the optical transmitter chooses the most suitable modulation format in order to achieve optimal transmission performance. Owing to the ability of switching among different modulation formats, flexible optical transmitters based on reconfigurable optical devices are becoming a key component for the implementation of future flexible optical networks. In this paper, we experimentally demonstrate a flexible 8-ary transmitter to achieve adaptive switching between 8-ary phase-shift keying (8PSK) and circular 8-ary quadrature amplitude modulation (8QAM) through reconfiguration of two cascaded in phase/quadrature (IQ) modulators with different driving signals and biasing conditions. An arbitrary binary quadrature-amplitude modulation (2QAM) with constant or non-constant amplitude is proposed and experimentally demonstrated using an IQ modulator. Then, optical 8PSK or 8QAM modulation formats are successfully synthesized when a standard squared QPSK modulator is cascaded with a constant-amplitude or non-constant-amplitude 2QAM, respectively. PMID- 26367985 TI - Flexible liquid metal-filled metamaterial absorber on polydimethylsiloxane (PDMS). AB - In this paper, we propose a novel flexible metamaterial (MM) absorber. The conductive pattern consists of liquid metal eutectic gallium indium alloy (EGaIn) enclosed in elastomeric microfluidic channels. Polydimethylsiloxane (PDMS) material is used as a supporting substrate. The proposed MM absorber is flexible because of its liquid metal and PDMS substrate. Numerical simulations and experimental results are presented when the microfluidic channels are filled with liquid metal. In order to evaluate the proposed MM absorber's performance, the fabricated absorber prototype is tested with rectangular waveguides. Almost perfect absorptivity is achieved at a resonant frequency of 8.22 GHz. PMID- 26367986 TI - Security risk of diffractive-imaging-based optical cryptosystem. AB - The well-known diffractive-imaging-based optical cryptosystem is breached in the paper. The decryption key of the system can be easily accessed by the opponent by using a new type of powerful phase retrieval method. Our result, to our best knowledge, is the first work to show the security risk of the diffractive-image cryptosystem. Meanwhile, we provide a set of numerical simulations to demonstrate the feasibility and robustness of the presented method. PMID- 26367987 TI - Towards femtosecond laser written arrayed waveguide gratings. AB - The fabrication of arrayed waveguide gratings (AWGs) using the femtosecond laser direct-write technique is investigated. We successfully demonstrate the fabrication of large planar waveguides that act as 2D free propagation zones. These slabs were found to have a highly uniform refractive index with a standard deviation of 1.97% relative to the total index contrast. The incorporation of low loss linear adiabatic tapers resulted in an increase of transmission by 90%. Strategies for manufacturing integrated laser written AWGs using continuous contouring to avoid lossy defects are discussed and demonstrated. PMID- 26367988 TI - Wavefront detection method of a single-sensor based adaptive optics system. AB - In adaptive optics system (AOS) for optical telescopes, the reported wavefront sensing strategy consists of two parts: a specific sensor for tip-tilt (TT) detection and another wavefront sensor for other distortions detection. Thus, a part of incident light has to be used for TT detection, which decreases the light energy used by wavefront sensor and eventually reduces the precision of wavefront correction. In this paper, a single Shack-Hartmann wavefront sensor based wavefront measurement method is presented for both large amplitude TT and other distortions' measurement. Experiments were performed for testing the presented wavefront method and validating the wavefront detection and correction ability of the single-sensor based AOS. With adaptive correction, the root-mean-square of residual TT was less than 0.2 lambda, and a clear image was obtained in the lab. Equipped on a 1.23-meter optical telescope, the binary stars with angle distance of 0.6" were clearly resolved using the AOS. This wavefront measurement method removes the separate TT sensor, which not only simplifies the AOS but also saves light energy for subsequent wavefront sensing and imaging, and eventually improves the detection and imaging capability of the AOS. PMID- 26367989 TI - Chip-integrated all-optical 4-bit Gray code generation based on silicon microring resonators. AB - We propose and experimentally demonstrate a 4-port passive encoder for 4-bit Gray code on pure silicon platform. The operation principle for this device is the thermo-optic (TO) effect in silicon microring resonator (MRR) whose transmission spectrum could be shifted by injecting strong light power. Therefore, the output powers of both the through-port and drop-port of the MRR could be controllable and switchable. Two threshold powers are defined to decide the port output code of bit "0" or "1". By combining two independent resonant wavelengths of two MRRs and adjusting their powers in a certain order, all-optical 4-bit Gray code generation has been successfully demonstrated. The proposed integrated device is competent in on-chip all-optical communication and optical interconnection systems with significant advantages, such as simple operation, compact size, economical fabrication process and great scalability. PMID- 26367990 TI - Passive harmonic hybrid mode-locked fiber laser with extremely broad spectrum. AB - We demonstrate a harmonic mode-locking Erbium-doped fiber laser which is cooperatively mode-locked by nonlinear polarization evolution (NPE) and semiconductor saturable absorber mirror (SESAM). Via effective dispersion and nonlinearity optimization, 8th harmonic at a repetition rate of 666.7 MHz is obtained. The output pulses has a full spectrum width at half maximum (FWHM) of 181 nm and duration of 218 fs. The pulses are compressed to 91 fs by external chirp compensation. The average power of the direct output pulse at an available pump power of 1.5 W is 136 mW, which exhibits a single-pulse energy of 0.2 nJ. The cavity super-mode suppression is up to 60 dB and the signal-to-noise ratio of the 8th harmonic is over 75 dB. PMID- 26367991 TI - Spoof localized surface plasmons in corrugated ring structures excited by microstrip line. AB - We have investigated the fundamental and high-order spoof localized surface plasmons (LSPs) modes in the proposed corrugated ring resonator printed on a thin dielectric substrate with or without ground plane. An efficient and ease-of integration method to excite spoof LSPs in the textured ring resonator has been adopted to suppress unwanted high-order modes and enhance fundamental modes. A multi-band-pass filter has been proposed and numerically demonstrated. Experimental results at the microwave frequencies verify the high performances of the corrugated ring resonator and the filter, showing great agreements with the simulation results. We have also shown that the fabricated device is sensitive to the variation of the refraction index of materials under test, even when the material is as thin as paper. PMID- 26367992 TI - Switchable viewing angle display with a compact directional backlight and striped diffuser. AB - A compact high-directionality backlight module combined with a striped diffuser is proposed to achieve an adjustable viewing angle for eco-display. The micro prisms on the compact light guide plate guide the emitting rays to the normal viewing angle, whereas a set of striped diffusers scatter the rays to a wide viewing angle. View cones of +/- 10 degrees / +/- 55 degrees were obtained for narrow/wide viewing modes with 88% / 85% uniformity of spatial luminance, respectively. Compared with the conventional backlight, the optical efficiencies were increased by factors of 1.47 and 1.38 in narrow and wide viewing modes, respectively. In addition, only 5% of power consumption was needed when the backlight worked in private narrow viewing mode to maintain the same luminance as that of a conventional backlight. PMID- 26367993 TI - Realistic loss estimation due to the mirror surfaces in a 10 meters-long high finesse Fabry-Perot filter-cavity. AB - In order to benefit over the entire frequency range from the injection of squeezed vacuum light at the output of laser gravitational wave detectors, a small bandwidth high finesse cavity is required. In this paper, we investigate the light losses due to the flatness and the roughness of realistic mirrors in a 10 meters-long Fabry-Perot filter cavity. Using measurements of commercial super polished mirrors, we were able to estimate the cavity round trip losses separating the loss contribution from low and high spatial frequencies. By careful tuning of the cavity g-factor and the incident position of the light on the mirrors, round trip losses due to imperfect mirror surfaces as low as 3 ppm can be achieved in the simulations. PMID- 26367994 TI - Guided mode caused by silicon nanopillar array for light emission enhancement in color-converting LED. AB - Plasmonic metallic nanostructures have been demonstrated an effective way to enhance the light emission efficiency in LEDs. Here, we propose a design of white LEDs that combining dielectric silicon nanopillar array in the color-converting layer. By investigating theoretically the guided mode caused by the nanopillar array-waveguide system, we demonstrate that the silicon nanopillar arrays enable larger near-field enhancement and more efficient photons emission property than the plasmonic counterparts. These performances make the silicon nanopillar arrays have potential application in light converter for efficient white LEDs. We also show that the guided mode can be controlled by changing the period of nanopillar grating and the thickness of polymer layer. More significant performance can be achieved by further optimizing the shape and size of the silicon nanoparticles. Compared with the square nanoparticle arrays, the hexagonal nanopillar arrays are demonstrated to have larger field enhancement and emission enhancement. Our research is expected to give insights into the design and optimization of the solid-state lighting systems by using silicon nanostructures, and the all dielectric metamaterials for gaining or lasing devices. PMID- 26367995 TI - Actively Q-switched ytterbium-doped fiber laser by an all-optical Q-switcher based on graphene saturable absorber. AB - We demonstrate an all-optical Q-switcher based on graphene saturable absorber (GSA). Due to the cross absorption modulation (XAM) effect in graphene, we can change the transmittance of signal light periodically by introducing a train of laser pulses into graphene. This allows controlling the Q-factor of the cavity. This Q-switcher has many advantages such as all-fiber structure, all-optical modulation, broadband applications. With this Q-switcher, we have successfully fabricated an actively Q-switched ytterbium-doped fiber laser. The pulse repetition rate can be tuned from 30.32 kHz to 101.29 kHz. What's more, synchronization of the Q-switched laser pulses and modulation laser pulses can be realized, which has many potential applications such as nonlinear frequency conversion, multi-color pump probe spectroscopy and Raman scattering spectroscopy. PMID- 26367996 TI - Carrier-envelope-phase insensitivity in high-order harmonic generation driven by few-cycle laser pulses. AB - We present evidence for self-stabilization of the relative spectral phase of high order harmonic emission against intensity variations of the driving field. Our results demonstrate that, near the laser focus, phase matching of the harmonic field from a macroscopic target can compensate for the intensity dependence of the intrinsic phase of the harmonics emitted by a single radiator. As a consequence, we show experimentally and theoretically the insensitivity of the harmonic spectra produced at the laser focus against variations of the carrier envelope phase (CEP) of a sub-two-cycle driving field. In addition, the associated attosecond pulse trains exhibit phase locking against CEP changes of the few-cycle driver. PMID- 26367997 TI - OFT sectorization approach to analysis of optical scattering in mercurous chloride single crystals. AB - This paper is devoted to the application of the optical Fourier transform (OFT) for the study and evaluation of optical scattering in the latest generation of calomel single crystals ready for application in several possible devices such as IR polarizers and acoustooptic tunable filters (AOTF). There are numerous effects that are responsible for the scattering of optical wave passing through the crystal sample volume and surface layers because they affect the optical crystal quality. The scattering level is a crucial and limiting parameter in many technical applications of the evaluated crystal. The proposed approach is based upon the high dynamic range optical FT configuration, creating the amplitude spectrum in the focal plane and its spatial angular distribution analysis based on the spectrum sectorization. The optical scattering pattern was tested in nine locations within each crystal sample volume and on numerous crystal samples. The experimental results are presented and discussed. PMID- 26367998 TI - Tunable frequency combs based on dual microring resonators. AB - In order to achieve efficient parametric frequency comb generation in microresonators, external control of coupling between the cavity and the bus waveguide is necessary. However, for passive monolithically integrated structures, the coupling gap is fixed and cannot be externally controlled, making tuning the coupling inherently challenging. We design a dual-cavity coupled microresonator structure in which tuning one ring resonance frequency induces a change in the overall cavity coupling condition. We demonstrate wide extinction tunability with high efficiency by engineering the ring coupling conditions. Additionally, we note a distinct dispersion tunability resulting from coupling two cavities of slightly different path lengths, and present a new method of modal dispersion engineering. Our fabricated devices consist of two coupled high quality factor silicon nitride microresonators, where the extinction ratio of the resonances can be controlled using integrated microheaters. Using this extinction tunability, we optimize comb generation efficiency as well as provide tunability for avoiding higher-order mode-crossings, known for degrading comb generation. The device is able to provide a 110-fold improvement in the comb generation efficiency. Finally, we demonstrate open eye diagrams using low-noise phase locked comb lines as a wavelength-division multiplexing channel. PMID- 26367999 TI - A comb laser-driven DWDM silicon photonic transmitter based on microring modulators. AB - We demonstrate concurrent multi-channel transmission at 10 Gbps per channel of a DWDM silicon photonic transmitter. The DWDM transmitter is based on a single quantum dot comb laser and an array of microring resonator-based modulators. The resonant wavelengths of microrings are thermally tuned to align with the wavelengths provided by the comb laser. No obvious crosstalk is observed at 240 GHz channel spacing. PMID- 26368000 TI - A calorimetric and spectroscopic comparison of the effects of cholesterol and its immediate biosynthetic precursors 7-dehydrocholesterol and desmosterol on the thermotropic phase behavior and organization of dipalmitoylphosphatidylcholine bilayer membranes. AB - We performed differential scanning calorimetric (DSC) and Fourier transform infrared (FTIR) spectroscopic studies of the effects of cholesterol (CHOL), 7 dehydrocholeterol (7DHC) and desmosterol (DES) on the thermotropic phase behavior and organization of dipalmitoylphosphatidylcholine (DPPC) bilayer membranes. 7DHC and DES are the immediate biosynthetic precursors of CHOL in the Kandutch-Russell and Bloch pathways and 7DHC and DES differ in structure from CHOL only by the presence of an additional double bond at C7 of ring B or C24 of the alkyl side chain, respectively. Our DSC results indicate that the incorporation of all three sterols produces comparable decreases in the temperature of the pretransition of DPPC, but CHOL decreases its cooperativity and enthalpy more strongly than 7DHC and especially DES. These findings indicate that all three sterols decrease the thermal stability of gel phase DPPC bilayers but that 7DHC and especially DES are less miscible in them. However, the incorporation of CHOL and DES produce comparable increases in the temperature of the broad component of the main phase transition of DPPC while 7DHC decreases it, but again CHOL produces greater decreases in its cooperativity and enthalpy then 7DHC and especially DES. These results indicate that CHOL and DES stabilize the sterol-rich domains of fluid DPPC bilayers, but that 7DHC and especially DES are less miscible in them. Our FTIR spectroscopic results indicate that CHOL increases the rotational conformational order of fluid DPPC bilayers to a somewhat and markedly greater degree than DES and 7DHC, respectively, consistent with our DSC findings. Our spectroscopic results also indicate that although all three sterols produce comparable degrees of H-bonding (hydration) of the DPPC ester carbonyl groups in fluid bilayers, CHOL is again found to be fully soluble in gel state DPPC bilayers at low temperatures, whereas 7DHC and especially DES are not. In general, we find that 7DHC and DES incorporation produce considerably different effects on DPPC bilayer membranes. In particular, the presence of an additional double bond at C7 or C24 produces a marked reduction in the ability of 7DHC to order fluid DPPC bilayers and in the miscibility of DES in such bilayers, respectively. These different effects may be the biophysical basis for the reduction of these double bonds in the last steps of CHOL biosynthesis, and for the deleterious biological effects of the accumulation of these sterols in vivo. PMID- 26368001 TI - Type I interferons for induction of remission in ulcerative colitis. AB - BACKGROUND: Interferons (IFNs) are cytokines which possess immunoregulatory properties and have been used to successfully treat a number of chronic inflammatory disorders. It has been postulated that Type I IFNs may be able to re establish the Th1/Th2 balance in Th2 predominant diseases like ulcerative colitis. OBJECTIVES: To systematically evaluate the efficacy and safety of type I IFN therapy for induction of remission in ulcerative colitis. SEARCH METHODS: We searched MEDLINE, EMBASE, CENTRAL, the Cochrane IBD/FBD group specialised register, and ClinicalTrials.gov from inception to August 8, 2014. Reference lists of trials and review articles, as well as recent proceedings from major gastroenterology meetings were manually searched. SELECTION CRITERIA: Randomised controlled trials of type I IFNs for induction of remission in UC were included. The study population included patients of any age with active ulcerative colitis. There were no exclusions based on type, dose or duration of IFN treatment. DATA COLLECTION AND ANALYSIS: Two independent authors reviewed studies for eligibility, extracted the data and assessed study quality using the Cochrane risk of bias tool. The overall quality of the evidence supporting the outcomes was evaluated using the GRADE criteria. The primary outcome was induction of remission of ulcerative colitis. Secondary outcomes included: time to remission, mean change in disease activity index score, clinical, histological or endoscopic improvement, improvement in quality of life, and adverse events. We calculated the risk ratio (RR) and corresponding 95% confidence interval (CI) for dichotomous outcomes. We calculated the mean difference and corresponding 95% confidence interval for continuous outcomes. Meta-analysis was performed using RevMan 5.3.5 software. MAIN RESULTS: Six studies were eligible for inclusion (517 patients). Five studies compared type I IFNs to placebo injections (485 patients) and a single study compared IFNs to prednisolone enemas in patients with left sided colitis (32 patients). The active comparator study was rated as high risk of bias due to an open-label design. Three studies were rated as unclear risk of bias for random sequence generation and allocation concealment. Two studies described as double blind were rated as unclear risk of bias for blinding. There was no significant benefit of type I IFNs over placebo for inducing clinical remission or improvement in patients with active ulcerative colitis. Thirty-six per cent (87/242) of patients in the type I IFNs group achieved clinical remission by 8 to 12 weeks compared to 30% (36/120) of placebo patients (RR 1.16, 95% CI 0.84 to 1.58; 4 studies, 362 patients). A GRADE analysis indicated that the overall quality of the evidence supporting the outcome clinical remission was moderate due to sparse data (123 events). Fifty-six per cent (149/264) of patients in the type I IFNs group improved clinically by 8 to 12 weeks compared to 48% (77/161) of placebo patients (RR 1.16, 95% CI 0.96 to 1.40; 4 studies, 425 patients). A GRADE analysis indicated that the overall quality of the evidence supporting the outcome clinical improvement was moderate due to sparse data (226 events). Patients who received type I IFNs were significantly more likely to withdraw from the studies due to adverse events than those who received placebo. Seven per cent (18/42) of type I IFNs patients withdrew due to adverse events compared to 2% (3/152) of placebo patients (RR 3.16, 95% CI 1.06 to 9.40). A GRADE analysis indicated that the overall quality of the evidence supporting the outcome withdrawal due to adverse events was low due to very sparse data (21 events). The study comparing type I IFNs to prednisolone enemas found no difference between the treatment groups in quality of life or disease activity scores. Common adverse events included headaches, arthralgias, myalgias, fatigue, back pain, nausea, application site reactions, rigors, and fevers. There were no statistically significant differences in the other secondary outcomes. AUTHORS' CONCLUSIONS: Moderate quality evidence suggests that type I IFNs are not effective for the induction of remission in UC. In addition, there are concerns regarding the tolerability of this class of treatment. PMID- 26368002 TI - Debridement for venous leg ulcers. AB - BACKGROUND: Venous ulcers (also known as varicose or venous stasis ulcers) are a chronic, recurring and debilitating condition that affects up to 1% of the population. Best practice documents and expert opinion suggests that the removal of devitalised tissue from venous ulcers (debridement) by any one of six methods helps to promote healing. However, to date there has been no review of the evidence from randomised controlled trials (RCTs) to support this. OBJECTIVES: To determine the effects of different debriding methods or debridement versus no debridement, on the rate of debridement and wound healing in venous leg ulcers. SEARCH METHODS: In February 2015 we searched: The Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE and EBSCO CINAHL. There were no restrictions with respect to language, date of publication or study setting. In addition we handsearched conference proceedings, journals not cited in MEDLINE, and the bibliographies of all retrieved publications to identify potential studies. We made contact with the pharmaceutical industry to enquire about any completed studies. SELECTION CRITERIA: We included RCTs, either published or unpublished, which compared two methods of debridement or compared debridement with no debridement. We presented study results in a narrative form, as meta-analysis was not possible. DATA COLLECTION AND ANALYSIS: Independently, two review authors completed all study selection, data extraction and assessment of trial quality; resolution of disagreements was completed by a third review author. MAIN RESULTS: We identified 10 RCTs involving 715 participants. Eight RCTs evaluated autolytic debridement and included the following agents or dressings: biocellulose wound dressing (BWD), non-adherent dressing, honey gel, hydrogel (gel formula), hydrofibre dressing, hydrocolloid dressings, dextranomer beads, Edinburgh University Solution of Lime (EUSOL) and paraffin gauze. Two RCTs evaluated enzymatic preparations and one evaluated biosurgical debridement. No RCTs evaluated surgical, sharp or mechanical methods of debridement, or debridement versus no debridement. Most trials were at a high risk of bias.Three RCTs assessed the number of wounds completely debrided. All three of these trials compared two different methods of autolytic debridement (234 participants), with two studies reporting statistically significant results: one study (100 participants) reported that 40/50 (80%) ulcers treated with dextranomer beads and 7/50 (14%) treated with EUSOL achieved complete debridement (RR 5.71, 95% CI 2.84 to 11.52); while the other trial (86 participants) reported the number of ulcers completely debrided as 31/46 (76%) for hydrogel versus 18/40 (45%) for paraffin gauze (RR 0.67, 95% CI 0.45 to 0.99). One study (48 participants) reported that by 12 weeks, 15/18 (84%) ulcers treated with BWD had achieved a 75% to 100% clean, granulating wound bed versus 4/15 (26%) treated with non-adherent petrolatum emulsion-impregnated gauze.Four trials assessed the mean time to achieve debridement: one (86 participants) compared two autolytic debridement methods, two compared autolytic methods with enzymatic debridement (71 participants), and the last (12 participants) compared autolytic with biosurgical debridement; none of the results achieved statistical significance.Two trials that assessed autolytic debridement methods reported the number of wounds healed at 12 weeks. One trial (108 participants) reported that 24/54 (44%) ulcers treated with honey healed versus 18/54 (33%) treated with hydrogel (RR (adjusted for baseline wound diameter) 1.38, 95% CI 1.02 to 1.88; P value 0.037). The second trial (48 participants) reported that 7/25 (28%) ulcers treated with BWD healed versus 7/23 (30%) treated with non-adherent dressing.Reduction in wound size was assessed in five trials (444 participants) in which two autolytic methods were compared. Results were statistically significant in one three-armed trial (153 participants) when cadexomer iodine was compared to paraffin gauze (mean difference 24.9 cm2, 95% CI 7.27 to 42.53, P value 0.006) and hydrocolloid compared to paraffin gauze (mean difference 23.8 cm2, 95% CI 5.48 to 42.12, P value 0.01). A second trial that assessed reduction in wound size based its results on median differences and, at four weeks, produced a statistically significantly result that favoured honey over hydrogel (P value < 0.001). The other three trials reported no statistically significant results for reduction in wound size, although one trial reported that the mean percentage reduction in wound area was greater at six and 12 weeks for BWD versus a non-adherent dressing (44% versus 24% week 6; 74% versus 54% week 12).Pain was assessed in six trials (544 participants) that compared two autolytic debridement methods, but the results were not statistically significant. No serious adverse events were reported in any trial. AUTHORS' CONCLUSIONS: There is limited evidence to suggest that actively debriding a venous leg ulcer has a clinically significant impact on healing. The overall small number of participants, low number of studies and lack of meta-analysis in this review precludes any strong conclusions of benefit. Comparisons of different autolytic agents (hydrogel versus paraffin gauze; Dextranomer beads versus EUSOL and BWD versus non-adherent dressings) and Larvae versus hydrogel all showed statistically significant results for numbers of wounds debrided. Larger trials with follow up to healing are required. PMID- 26368003 TI - A National Survey of Pulmonologists' Views on Low-Dose Computed Tomography Screening for Lung Cancer. AB - RATIONALE: Multiple guidelines now recommend low-dose computed tomography (LDCT) screening for lung cancer. Given their central role in the planning of LDCT screening programs, pulmonologists' beliefs about LDCT screening will affect the safety, cost-effectiveness, and success of LDCT screening implementation. OBJECTIVES: To assess pulmonologists' propensity to offer lung cancer screening and their perceptions about LDCT screening. METHODS: We performed a national web based survey, administered July 2013 to February 2014, among all staff pulmonologists active in Veterans Health Administration pulmonary clinics. The primary outcome was screening propensity (on the basis of responses to clinical vignettes) in relation to guidelines. Using bivariate and multinomial logistic regression, we assessed how perceptions of the evidence, trade-offs, and barriers to implementation of LDCT screening programs affected propensity to screen. MEASUREMENTS AND MAIN RESULTS: Of 573 eligible pulmonologists e-mailed, 286 (49.9%) participated. Approximately one-half (52.4%) had a propensity for guideline-concordant screening, 22.7% for overscreening, and 24.9% for underscreening. In bivariate analyses, guideline concordance was associated with acceptance of trial evidence, guidelines, and the efficacy of screening. In multivariable models, underscreeners were more likely to cite the potential harms of screening (e.g., false-positive findings, radiation exposure, incidental findings, unfavorable cost-benefit ratio), as influential factors (relative risk, 3.9; 95% confidence interval, 1.5-9.67) and were less influenced by trial evidence and guidelines (relative risk, 0.06; 95% confidence interval, 0.02-0.2), as compared with guideline-concordant screeners. Local resource availability did not significantly affect screening propensity, but insufficient infrastructure and personnel were commonly perceived barriers to implementation. CONCLUSIONS: Pulmonologists have varied perceptions of the evidence and trade-offs of LDCT screening, leading to the potential for over- and underscreening. To minimize potential harms as LDCT screening is widely implemented, physicians must understand which patients are appropriate candidates and engage those patients in a shared decision-making process regarding the trade-offs of LDCT screening. PMID- 26368004 TI - Computational Identification of Post Translational Modification Regulated RNA Binding Protein Motifs. AB - RNA and its associated RNA binding proteins (RBPs) mitigate a diverse array of cellular functions and phenotypes. The interactions between RNA and RBPs are implicated in many roles of biochemical processing by the cell such as localization, protein translation, and RNA stability. Recent discoveries of novel mechanisms that are of significant evolutionary advantage between RBPs and RNA include the interaction of the RBP with the 3' and 5' untranslated region (UTR) of target mRNA. These mechanisms are shown to function through interaction of a trans-factor (RBP) and a cis-regulatory element (3' or 5' UTR) by the binding of a RBP to a regulatory-consensus nucleic acid motif region that is conserved throughout evolution. Through signal transduction, regulatory RBPs are able to temporarily dissociate from their target sites on mRNAs and induce translation, typically through a post-translational modification (PTM). These small, regulatory motifs located in the UTR of mRNAs are subject to a loss-of-function due to single polymorphisms or other mutations that disrupt the motif and inhibit the ability to associate into the complex with RBPs. The identification of a consensus motif for a given RBP is difficult, time consuming, and requires a significant degree of experimentation to identify each motif-containing gene on a genomic scale. We have developed a computational algorithm to analyze high throughput genomic arrays that contain differential binding induced by a PTM for a RBP of interest-RBP-PTM Target Scan (RPTS). We demonstrate the ability of this application to accurately predict a PTM-specific binding motif to an RBP that has no antibody capable of distinguishing the PTM of interest, negating the use of in vitro exonuclease digestion techniques. PMID- 26368005 TI - Steric C-N bond activation on the dimeric macrocycle [{P(MU-NR)}2(MU-NR)]2. AB - Dimeric cyclophosphazanes [{P(MU-NR)}2(MU-NR)]2 [R = (t)Bu ( 1) and iPr ( 3)] were oxidized with elemental selenium. During these reactions an unexpected C-N bond cleavage and N-H bond formation occurred. Compound 1 produced P4(MU N(t)Bu)3(MU-NH)3Se4 ( 2) where three tBu groups were lost in the form of isobutylene. In contrast, during the oxidation of the less sterically hindered 3, the resulting product, P4(MU-N(i)Pr)5(MU-NH)Se4 ( 4), showed only one substituent loss. Theoretical studies confirmed the steric nature of the driving force underlying the different outcomes. PMID- 26368006 TI - Genetic diversity within the botulinum neurotoxin-producing bacteria and their neurotoxins. AB - The recent availability of multiple Clostridium botulinum genomic sequences has initiated a new genomics era that strengthens our understanding of the bacterial species that produce botulinum neurotoxins (BoNTs). Analysis of the genomes has reinforced the historical Group I-VI designations and provided evidence that the bont genes can be located within the chromosome, phage or plasmids. The sequences provide the opportunity to examine closely the variation among the toxin genes, the composition and organization of the toxin complex, the regions flanking the toxin complex and the location of the toxin within different bacterial strains. These comparisons provide evidence of horizontal gene transfer and site-specific insertion and recombination events that have contributed to the variation observed among the neurotoxins. Here, examples that have contributed to the variation observed in serotypes A-H strains are presented to illustrate the mechanisms that have contributed to their variation. PMID- 26368007 TI - Aesthetic use of BoNT: Options and outcomes. AB - There are a multitude of uses for BoNT in the aesthetic realm. Efficacy has been shown in softening glabellar creases, crows feet, forehead rhytides, and in correcting facial asymmetries, including mild eyelid ptosis. Facial shape can be altered through injections of BoNT into masseter, and smiles can be altered with BoNT. Clinical examples of the above will be shown, as well as adverse outcomes with inaccurate injection techniques. PMID- 26368008 TI - The Network Structure of Symptoms of the Diagnostic and Statistical Manual of Mental Disorders. AB - Although current classification systems have greatly contributed to the reliability of psychiatric diagnoses, they ignore the unique role of individual symptoms and, consequently, potentially important information is lost. The network approach, in contrast, assumes that psychopathology results from the causal interplay between psychiatric symptoms and focuses specifically on these symptoms and their complex associations. By using a sophisticated network analysis technique, this study constructed an empirically based network structure of 120 psychiatric symptoms of twelve major DSM-IV diagnoses using cross sectional data of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC, second wave; N = 34,653). The resulting network demonstrated that symptoms within the same diagnosis showed differential associations and indicated that the strategy of summing symptoms, as in current classification systems, leads to loss of information. In addition, some symptoms showed strong connections with symptoms of other diagnoses, and these specific symptom pairs, which both concerned overlapping and non-overlapping symptoms, may help to explain the comorbidity across diagnoses. Taken together, our findings indicated that psychopathology is very complex and can be more adequately captured by sophisticated network models than current classification systems. The network approach is, therefore, promising in improving our understanding of psychopathology and moving our field forward. PMID- 26368009 TI - HIF2A Variants Were Associated with Different Levels of High-Altitude Hypoxia among Native Tibetans. AB - Hypoxia inducible factors, including HIF1A and HIF2A, play central roles in response to high-altitude hypoxia and genetic variants of HIF1A or HIF2A were associated with high-altitude sickness or adaptation. However, it remains to determine whether they are associated with tolerance to different levels of high altitude selection pressure among native Tibetans. We recruited 189 Tibetan subjects living at 2,700 meters (Low level of high altitude, LHA), 197 at 3,200 meters (Middle level of high altitude of high altitude, MHA), 249 at 3,700 meters (High level of high altitude, HHA) and 269 at 4,700 meters (Very high level of high altitude, VHA) and performed association analysis of twelve tSNPs (tagging SNPs) in HIF1A and HIF2A with high-altitude. We found (1) a increasing trend of HIF2A rs5621780-C(18.4%, 15.9%, 32.8% and 31.1%, respectively, in LHA, MHA, HHA and VHA)(P = 3.56E-9); (2) increasing trends of HIF2A rs6756667-A(68.7%, 73.4%, 79.9% and 89.6%), rs7589621- G(74.6%, 77.9%, 83.7%, and 92.1%) and rs1868092 A(64.1%, 67.3%, 75.1% and 84.4%) (P = 3.56E-9, 4.68E-16, 1.17E-13 and 7.09E-14, respectively); (3) a increasing trend of haplotype AG (68.7%, 73.1%, 79.9% and 89.6%) (P = 2.22E-7) which was constructed by rs6756667 and rs7589621; (4) a strong linear correlation between major alleles of rs6756667-A (R2 = 0.997, P = 0.002), rs7589621-G (R2 = 0.994, P = 0.003), rs1868092-A (R2 = 0.985, P = 0.008) and altitude by linear correlation test. The associations between HIF2A variants and different level of high altitude support that extremely high-altitude hypoxia challenge imposes selective effects on HIF2A variants among native Tibetans. PMID- 26368010 TI - Associations between maternal serum free beta human chorionic gonadotropin (beta hCG) levels and adverse pregnancy outcomes. AB - The objective was to determine the strength of relationship between maternal free beta human chorionic gonadotropin (beta-hCG) concentrations and rates of adverse pregnancy outcomes. Consecutive records of the database of our Down screening project were assessed for free beta-hCG levels and pregnancy outcomes. Pregnancies with foetal chromosomal or structural anomalies and those with underlying disease were excluded. Free beta-hCG levels of < 0.5, > 0.5 and < 2.0, and >= 2.0 MoM were categorised as low, normal and high, respectively. Of 17,082 screened women, 13,620 were available for analysis. In the first trimester (n = 8150), low beta-hCG levels significantly increased risk for intrauterine growth restriction (IUGR), preterm birth, low birth weight (LBW) and low Apgar score with relative risk of 1.66, 1.43, 1.83 and 2.89; whereas high beta-hCG group had a significant decreased risk of preterm birth and GDM with relative risk of 0.73 and 0.62. In the second trimester (n = 5470), both low and high beta-hCG groups had significant increased risks of the most common adverse outcomes, i.e. spontaneous abortion, IUGR and preterm birth. In conclusion, abnormally low (< 0.5MoM) or high (> 2.0 MoM) free beta-hCG levels are generally associated with an increased risk of adverse pregnancy outcomes. Nevertheless, high free beta-hCG levels in the first trimester may possibly decrease risk of preterm delivery and GDM. PMID- 26368012 TI - Opportunities for Nurses to Increase Parental Health Literacy: A Discussion Paper. AB - Most families can access a range of health information and advice. Information and advice sources often include nurses, the Internet, social media, books, as well as family and friends. While the immediate aim may be to find information, it can also be to assist with parenting skills, solve parenting problems or as part of decision-making processes about their child's health. These processes are strongly influenced by the parent's level of health literacy. Health literacy describes a person's capacity to obtain and utilize health related information. Although there are numerous health literacy definitions all have clearly defined steps. These steps are: obtaining relevant information; then understanding this information; and finally being able to use the information to achieve the expected outcome. Previous research has linked low levels of parental health literacy with poorer child health outcomes. Given this link, increasing health literacy levels would be advantageous for both families and health services. Nurses working with families are in a position to support the family to increase their health literacy through the use of a variety of strategies. This article outlines how health literacy can influence the way parents seek help when they are concerned about child health issues, the relevance of parental health literacy for nurses and suggests some tools that could be used to support the increase of health literacy. PMID- 26368011 TI - Fat Grafting in Burn Scar Alleviates Neuropathic Pain via Anti-Inflammation Effect in Scar and Spinal Cord. AB - Burn-induced neuropathic pain is complex, and fat grafting has reportedly improved neuropathic pain. However, the mechanism of fat grafting in improving neuropathic pain is unclear. Previous investigations have found that neuroinflammation causes neuropathic pain, and anti-inflammatory targeting may provide potential therapeutic opportunities in neuropathic pain. We hypothesized that fat grafting in burn scars improves the neuropathic pain through anti inflammation. Burn-induced scar pain was confirmed using a mechanical response test 4 weeks after burn injuries, and autologous fat grafting in the scar area was performed simultaneously. After 4 weeks, the animals were sacrificed, and specimens were collected for the inflammation test, including COX-2, iNOS, and nNOS in the injured skin and spinal cord dorsal horns through immunohistochemistry and Western assays. Furthermore, pro-inflammatory cytokines (IL-1 beta and TNF-alpha) in the spinal cord were collected. Double immunofluorescent staining images for measuring p-IkappaB, p-NFkappaB, p-JNK, and TUNEL as well as Western blots of AKT, Bax/Bcl-2 for the inflammatory process, and apoptosis were analyzed. Fat grafting significantly reduced COX2, nNOS, and iNOS in the skin and spinal cord dorsal horns, as well as IL-1beta and TNF-alpha, compared with the burn group. Moreover, regarding the anti-inflammatory effect, the apoptosis cells in the spinal cord significantly decreased after the fat grafting in the burn injury group. Fat grafting was effective in treating burn induced neuropathic pain through the alleviation of neuroinflammation and ameliorated spinal neuronal apoptosis. PMID- 26368013 TI - Correction: Socio-Economic Differentials in Impoverishment Effects of Out-of Pocket Health Expenditure in China and India: Evidence from WHO SAGE. PMID- 26368014 TI - A model evaluation study for treatment planning of laser-induced thermal therapy. AB - A cross-validation analysis evaluating computer model prediction accuracy for a priori planning magnetic resonance-guided laser-induced thermal therapy (MRgLITT) procedures in treating focal diseased brain tissue is presented. Two mathematical models are considered. (1) A spectral element discretisation of the transient Pennes bioheat transfer equation is implemented to predict the laser-induced heating in perfused tissue. (2) A closed-form algorithm for predicting the steady state heat transfer from a linear superposition of analytic point source heating functions is also considered. Prediction accuracy is retrospectively evaluated via leave-one-out cross-validation (LOOCV). Modelling predictions are quantitatively evaluated in terms of a Dice similarity coefficient (DSC) between the simulated thermal dose and thermal dose information contained within N = 22 MR thermometry datasets. During LOOCV analysis, the transient model's DSC mean and median are 0.7323 and 0.8001 respectively, with 15 of 22 DSC values exceeding the success criterion of DSC >= 0.7. The steady-state model's DSC mean and median are 0.6431 and 0.6770 respectively, with 10 of 22 passing. A one-sample, one sided Wilcoxon signed-rank test indicates that the transient finite element method model achieves the prediction success criteria, DSC >= 0.7, at a statistically significant level. PMID- 26368015 TI - A Single Amino Acid in the M1 Protein Responsible for the Different Pathogenic Potentials of H5N1 Highly Pathogenic Avian Influenza Virus Strains. AB - Two highly pathogenic avian influenza virus strains, A/duck/Hokkaido/WZ83/2010 (H5N1) (WZ83) and A/duck/Hokkaido/WZ101/2010 (H5N1) (WZ101), which were isolated from wild ducks in Japan, were found to be genetically similar, with only two amino acid differences in their M1 and PB1 proteins at positions 43 and 317, respectively. We found that both WZ83 and WZ101 caused lethal infection in chickens but WZ101 killed them more rapidly than WZ83. Interestingly, ducks experimentally infected with WZ83 showed no or only mild clinical symptoms, whereas WZ101 was highly lethal. We then generated reassortants between these viruses and found that exchange of the M gene segment completely switched the pathogenic phenotype in both chickens and ducks, indicating that the difference in the pathogenicity for these avian species between WZ83 and WZ101 was determined by only a single amino acid in the M1 protein. It was also found that WZ101 showed higher pathogenicity than WZ83 in mice and that WZ83, whose M gene was replaced with that of WZ101, showed higher pathogenicity than wild-type WZ83, although this reassortant virus was not fully pathogenic compared to wild-type WZ101. These results suggest that the amino acid at position 43 of the M1 protein is one of the factors contributing to the pathogenicity of H5N1 highly pathogenic avian influenza viruses in both avian and mammalian hosts. PMID- 26368016 TI - The diadinoxanthin diatoxanthin cycle induces structural rearrangements of the isolated FCP antenna complexes of the pennate diatom Phaeodactylum tricornutum. AB - The study investigated the influence of the xanthophyll cycle pigments diadinoxanthin (DD) and diatoxanthin (Dt) on the spectroscopic characteristics, structure and protein composition of isolated fucoxanthin chlorophyll protein (FCP) complexes of the pennate diatom Phaeodactylum tricornutum. 77 K fluorescence emission spectra revealed that Dt-containing FCP complexes showed a characteristic long wavelength fluorescence emission at 700 nm at a pH-value of 5 whereas DD-enriched FCPs retained the typical 680 nm fluorescence emission maximum of isolated FCPs. The 700 nm emission in Dt-containing FCPs indicates an aggregation of antenna complexes and is a typical feature of the quenching site Q1 in recent models for non-photochemical fluorescence quenching (NPQ). A comparable long-wavelength fluorescence emission was found in FCP complexes prepared with either triton X-100 or n-dodecyl beta-D-maltoside as detergent. A treatment of the FCP complexes at low pH-values in the presence of a high concentration of Mg(2+) ions showed that the extent of FCP aggregation which leads to the 700 nm fluorescence emission is different from the macro-aggregation of antenna complexes in higher plants. Protein analyses by mass spectrometry showed that the protein composition of the DD- and Dt-enriched FCP complexes was comparable. However, the Lhcf6 and Lhcr1 polypeptides were only found in Dt enriched FCPs isolated with dodecyl maltoside whereas the Lhcf17 protein was only detected in DD-enriched FCPs prepared with triton. With respect to low pH-induced antenna aggregation it is important that the Lhcx1 protein was found in both DD- and Dt-enriched FCPs, albeit with only two peptides with confident scores. PMID- 26368017 TI - SpBADH of the halophyte Sesuvium portulacastrum strongly confers drought tolerance through ROS scavenging in transgenic Arabidopsis. AB - Glycine betaine (GB) accumulation is involved in abiotic stress. However, it is not known whether BADH, the key enzyme of GB synthesis, utilizes the antioxidant system to confer drought stress tolerance. In this study, a novel member of the ALDH10 gene family, SpBADH, was isolated from Sesuvium portulacastrum. The expression of this gene was up-regulated by NaCl, PEG6000, H2O2, ABA and high temperature in S. portulacastrum. SpBADH overexpression in Arabidopsis resulted in higher BADH activity and GB content and might increase tolerance to drought/osmotic stresses, specifically strong tolerance to drought stress. Transgenic lines exhibited lower MDA and H2O2 contents but higher proline, POD, SOD and CAT contents than the wild type under drought and osmotic stresses. SpBADH overexpression in Arabidopsis also enhanced the expression of ROS-related genes including AtSOD, AtPOD, AtCAT, AtAPX and Atpsb under drought and osmotic stresses. Thus, SpBADH increases plant tolerance to drought or osmotic stresses by reducing H2O2, increasing proline, and activating antioxidative enzymes to improve ROS scavenging. PMID- 26368018 TI - Household Socioeconomic and Demographic Correlates of Cryptosporidium Seropositivity in the United States. AB - BACKGROUND: Cryptosporidium are parasitic protozoa that infect humans, domestic animals, and wildlife globally. In the United States, cryptosporidiosis occurs in an estimated 750,000 persons annually, and is primarily caused by either of the Cryptosporidium parvum genotypes 1 and 2, exposure to which occurs through ingestion of food or water contaminated with oocytes shed from infected hosts. Although most cryptosporidiosis cases are caused by genotype 1 and are of human origin, the zoonotic sources of genotype 2, such as livestock, are increasingly recognized as important for understanding human disease patterns. Social inequality could mediate patterns of human exposure and infection by placing individuals in environments where food or water contamination and livestock contact is high or through reducing the availability of educational and sanitary resources required to avoid exposure. METHODOLOGY/PRINCIPAL FINDINGS: We here analyzed data from the National Health and Nutritional Examination Survey (NHANES) between 1999 and 2000, and related seropositivity to Cryptosporidium parvum to correlates of social inequality at the household and individual scale. After accounting for the complex sampling design of NHANES and confounding by individual demographics and household conditions, we found impaired household food adequacy was associated with greater odds of Cryptosporidium seropositivity. Additionally, we identified individuals of non-white race and ethnicity and those born outside the United States as having significantly greater risk than white, domestic-born counterparts. Furthermore, we provide suggestive evidence for direct effects of family wealth on Cryptosporidium seropositivity, in that persons from low-income households and from families close to the poverty threshold had elevated odds of seropositivity relative to those in high-income families and in households far above the poverty line. CONCLUSIONS/SIGNIFICANCE: These results refute assertions that cryptosporidiosis in the United States is independent of social marginalization and poverty, and carry implications for targeted public health interventions for Cryptosporidium infection in resource poor groups. Future longitudinal and multilevel studies are necessary to elucidate the complex interactions between ecological factors, social inequality, and Cryptosporidium dynamics. PMID- 26368019 TI - Gypenosides Synergistically Enhances the Anti-Tumor Effect of 5-Fluorouracil on Colorectal Cancer In Vitro and In Vivo: A Role for Oxidative Stress-Mediated DNA Damage and p53 Activation. AB - OBJECTIVE: 5-Fluorouracil (5-Fu) has been widely used as a first-line drug for colorectal cancer (CRC) treatment but limited by drug resistance and severe toxicity. The chemo-sensitizers that augment its efficiency and overcome its limitation are urgently needed. Gypenosides (Gyp), the main components from Gynostemma pentaphyllum (Thunb.) Makino, has shown potential anti-tumor property with little side-effect. Here, we carefully explored the chemo-sensitization of Gyp to potentiate the anti-tumor effect of 5-Fu in vitro and in vivo. METHODOLOGY / PRINCIPAL FINDINGS: 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltertrazolium bromide tetrazolium assay and colony formation test reveal that Gyp could significantly enhance the 5-Fu-caused SW-480,SW-620 and Caco2 cells viability loss. Calcusyn analysis shows that Gyp acts synergistically with 5-Fu. Annexin V PE/7-AAD staining indicates 5-Fu + Gyp could induce SW-480 cell apoptosis. The activations of caspase 3, caspase 9 and poly (ADP-ribose) polymerase (PARP) were involved in the process. Gyp was also found to up-regulate 5-Fu-caused phospho p53 expression and thus augment 5-Fu-induced G0/G1 phase arrest. Gyp elevated intracellular ROS level, significantly enhanced 5-Fu-triggered DNA damage response as evidenced by flow cytometry, comet assay and the expression of Ser139 Histone H2A.X. Inhibition of ROS and p53 respectively reversed the cell death induced by 5-Fu + Gyp, suggesting the key roles of ROS and p53 in the process. Moreover, 5-Fu and Gyp in combination exhibits much superior tumor volume and weight inhibition on CT-26 xenograft mouse model in comparison to 5-Fu or Gyp alone. Immunohistochemistry analysis suggests the combinations greatly suppressed tumor proliferation. Preliminary toxicological results show that 5-Fu + Gyp treatment is relatively safe. CONCLUSIONS: As a potential chemo-sensitizer, Gyp displays a splendid synergistic effect with 5-Fu to inhibit cancer cell proliferation and tumor growth. By using 5-Fu and Gyp in combination would be a promising therapeutic strategy for CRC treatment. PMID- 26368020 TI - The Association of Handgrip Strength and Type 2 Diabetes Mellitus in Six Ethnic Groups: An Analysis of the HELIUS Study. AB - We investigated whether ethnic differences in handgrip strength, a marker of poor muscle strength and quality, is a potential cause of ethnic disparities in type 2 diabetes mellitus. We included 2086 Dutch, 2216 South Asian Surinamese, 2084 African Surinamese, 1786 Ghanaian, 2223 Turkish and 2199 Moroccan origin participants from the HELIUS study. We analyzed ethnic differences in handgrip strength, and its association with type 2 diabetes mellitus using logistic regression analyses adjusted for socio-demographic factors, body composition and lifestyle factors. Additionally, we investigated whether handgrip strength explained the ethnic differences in type 2 diabetes mellitus. We found that handgrip strength differed significantly across ethnic groups. After full adjustment, we found an inverse association with type 2 diabetes mellitus (OR 0.95; 95% CI 0.92-0.97) that did not differ substantially between ethnic groups, men and among women, and lean and overweight individuals. The association was not affected by the measure used to define type 2 diabetes mellitus, but was attenuated by exclusion of people with known diabetes. The ethnic differences in type 2 diabetes mellitus were not explained by handgrip strength (e.g. the OR for the South Asian Surinamese vs. Dutch changed from 5.03; 3.69-6.68 to 4.87; 3.57 6.65). In conclusion, we found large ethnic differences in handgrip strength and a consistent association of low handgrip strength with prevalent type 2 diabetes mellitus. This suggests that handgrip strength may be investigated as a target for intervention or a marker to identify people at risk of type 2 diabetes mellitus. PMID- 26368021 TI - Multimer Formation Explains Allelic Suppression of PRDM9 Recombination Hotspots. AB - Genetic recombination during meiosis functions to increase genetic diversity, promotes elimination of deleterious alleles, and helps assure proper segregation of chromatids. Mammalian recombination events are concentrated at specialized sites, termed hotspots, whose locations are determined by PRDM9, a zinc finger DNA-binding histone methyltransferase. Prdm9 is highly polymorphic with most alleles activating their own set of hotspots. In populations exhibiting high frequencies of heterozygosity, questions remain about the influences different alleles have in heterozygous individuals where the two variant forms of PRDM9 typically do not activate equivalent populations of hotspots. We now find that, in addition to activating its own hotspots, the presence of one Prdm9 allele can modify the activity of hotspots activated by the other allele. PRDM9 function is also dosage sensitive; Prdm9+/- heterozygous null mice have reduced numbers and less active hotspots and increased numbers of aberrant germ cells. In mice carrying two Prdm9 alleles, there is allelic competition; the stronger Prdm9 allele can partially or entirely suppress chromatin modification and recombination at hotspots of the weaker allele. In cell cultures, PRDM9 protein variants form functional heteromeric complexes which can bind hotspots sequences. When a heteromeric complex binds at a hotspot of one PRDM9 variant, the other PRDM9 variant, which would otherwise not bind, can still methylate hotspot nucleosomes. We propose that in heterozygous individuals the underlying molecular mechanism of allelic suppression results from formation of PRDM9 heteromers, where the DNA binding activity of one protein variant dominantly directs recombination initiation towards its own hotspots, effectively titrating down recombination by the other protein variant. In natural populations with many heterozygous individuals, allelic competition will influence the recombination landscape. PMID- 26368022 TI - Structure and Mechanism of a Viral Collagen Prolyl Hydroxylase. AB - The Fe(II)- and 2-oxoglutarate (2-OG)-dependent dioxygenases comprise a large and diverse enzyme superfamily the members of which have multiple physiological roles. Despite this diversity, these enzymes share a common chemical mechanism and a core structural fold, a double-stranded beta-helix (DSBH), as well as conserved active site residues. The prolyl hydroxylases are members of this large superfamily. Prolyl hydroxylases are involved in collagen biosynthesis and oxygen sensing in mammalian cells. Structural-mechanistic studies with prolyl hydroxylases have broader implications for understanding mechanisms in the Fe(II) and 2-OG-dependent dioxygenase superfamily. Here, we describe crystal structures of an N-terminally truncated viral collagen prolyl hydroxylase (vCPH). The crystal structure shows that vCPH contains the conserved DSBH motif and iron binding active site residues of 2-OG oxygenases. Molecular dynamics simulations are used to delineate structural changes in vCPH upon binding its substrate. Kinetic investigations are used to report on reaction cycle intermediates and compare them to the closest homologues of vCPH. The study highlights the utility of vCPH as a model enzyme for broader mechanistic analysis of Fe(II)- and 2-OG dependent dioxygenases, including those of biomedical interest. PMID- 26368023 TI - Toxic and essential elements in Nigerian rice and estimation of dietary intake through rice consumption. AB - In this study, levels and estimated daily intake (EDI) of two toxic elements, Cd and Pb, and eight essential elements: Ca, P, Zn, Mn, Co, Cu, Se and Mo, were determined in Nigerian rice samples. The mean levels of Cd, Pb and Co were 5.43+/ 0.88, 38.66+/-5.42, 25.8+/-3.18 ng/g. The mean levels of Ca, P, Zn, Mn, Cu, Se and Mo were 71.5+/-7.31, 951+/-52.0, 10.2+/-0.63, 8.5+/-0.47, 3.07+/-0.18, 40.1+/ 9.2 and 0.39+/-0.05 ug/g, respectively. The percentage contribution to the reference values for each element was 0.54, 7.71, 0.38, 9.51, 8.97, 31.3, 30.7, 5.1 and 60.7% for Cd, Pb, Ca, P, Zn, Mn, Cu, Se and Mo, respectively. The elemental nutrient levels in Nigerian rice samples are comparable to those obtained from other regions and their consumption does not pose any serious health risk to consumers. PMID- 26368025 TI - Contrast-enhanced ultrasound to assess plaque neovascularization in irradiated carotid arteries. PMID- 26368024 TI - Noninvasive Multimodal Imaging to Predict Recovery of Locomotion after Extended Limb Ischemia. AB - Acute limb ischemia is a common cause of morbidity and mortality following trauma both in civilian centers and in combat related injuries. Rapid determination of tissue viability and surgical restoration of blood flow are desirable, but not always possible. We sought to characterize the response to increasing periods of hind limb ischemia in a porcine model such that we could define a period of critical ischemia (the point after which irreversible neuromuscular injury occurs), evaluate non-invasive methods for characterizing that ischemia, and establish a model by which we could predict whether or not the animal's locomotion would return to baselines levels post-operatively. Ischemia was induced by either application of a pneumatic tourniquet or vessel occlusion (performed by clamping the proximal iliac artery and vein at the level of the inguinal ligament). The limb was monitored for the duration of the procedure with both 3-charge coupled device (3CCD) and infrared (IR) imaging for tissue oxygenation and perfusion, respectively. The experimental arms of this model are effective at inducing histologically evident muscle injury with some evidence of expected secondary organ damage, particularly in animals with longer ischemia times. Noninvasive imaging data shows excellent correlation with post-operative functional outcomes, validating its use as a non-invasive means of viability assessment, and directly monitors post-occlusive reactive hyperemia. A classification model, based on partial-least squares discriminant analysis (PLSDA) of imaging variables only, successfully classified animals as "returned to normal locomotion" or "did not return to normal locomotion" with 87.5% sensitivity and 66.7% specificity after cross-validation. PLSDA models generated from non-imaging data were not as accurate (AUC of 0.53) compared the PLSDA model generated from only imaging data (AUC of 0.76). With some modification, this limb ischemia model could also serve as a means on which to test therapies designed to prolong the time before critical ischemia. PMID- 26368026 TI - Long-term complication of the thoracic radiation in breast cancer: An complete atrioventricular block case. PMID- 26368027 TI - How do elite ski jumpers handle the dynamic conditions in imitation jumps? AB - We examined the effect of boundary conditions in imitation ski jumping on movement dynamics and coordination. We compared imitation ski jumps with--and without--the possibility to generate shear propulsion forces. Six elite ski jumpers performed imitation jumps by jumping from a fixed surface and from a rolling platform. The ground reaction force vector, kinematics of body segments, and EMG of eight lower limb muscles were recorded. Net joint dynamics were calculated using inverse dynamics. The two imitation jumps differed considerably from each other with regard to the dynamics (moments, forces), whereas the kinematics were very similar. Knee power was higher and hip power was lower on the rolling platform than on the fixed surface. Mean EMG levels were very similar for both conditions, but differences in the development of muscle activity were indicated for seven of eight muscles. These differences are reflected in a subtle difference of the alignment of ground reaction force with centre of mass: the ground reaction force runs continuously close to but behind the centre of mass on the rolling platform and fluctuates around it on the fixed surface. This likely reflects a different strategy for controlling angular momentum. PMID- 26368028 TI - Ischemia as a potential etiologic factor in idiopathic unilateral sudden sensorineural hearing loss: Analysis of posterior circulation arteries. AB - The association between idiopathic sudden sensorineural hearing loss (ISSNHL) and the radiologic characteristics of the vertebrobasilar artery is unclear. We hypothesized that the degree and direction of vertebrobasilar artery curvature in the posterior circulation contribute to the occurrence of ISSNHL. We consecutively enrolled patients diagnosed with unilateral ISSNHL in two tertiary hospitals. Magnetic resonance images were performed in all patients to exclude specific causes of ISSNHL, such as vestibular schwannoma, chronic mastoiditis, and anterior inferior cerebellar artery infarct. We measured the following parameters of posterior circulation: vertebral and basilar artery diameter, the degree of basilar artery curvature (modified smoker criteria), and vertebral artery dominance. Pure tone audiometries were performed at admission and again 1 week and 3 months later. A total of 121 ISSNHL patients (mean age, 46.0 +/- 17.3 years; 48.8% male) were included in these analyses. The proportion of patients with the left side hearing loss was larger than the proportion with the right side hearing loss (left, 57.9%; right, 42.1%). The majority of patients were characterized by a left dominant vertebral artery and right-sided basilar artery curvature. The direction of the basilar artery curvature was significantly associated with hearing loss lateralization (p = 0.036). Age and sex matched multivariable analyses revealed the absence of diabetes and right-sided basilar artery curvature as significant predictors for left sided hearing loss. There was no statistical difference between atherosclerotic cardiovascular risk score (high versus low) and hearing outcomes at 3 months. In ISSNHL, the laterality of hearing loss was inversely associated with the direction of basilar artery curvature. Our results, therefore, indicate the importance of vascular assessment when evaluating ISSNHL. PMID- 26368030 TI - The answers in our blood: finding new uses for a prenatal test in oncology. PMID- 26368029 TI - Speech-evoked ABR: Effects of age and simulated neural temporal jitter. AB - The speech-evoked auditory brainstem response (sABR) provides a measure of encoding complex stimuli in the brainstem, and this study employed the sABR to better understand the role of neural temporal jitter in the response patterns from older adults. In experiment 1, sABR recordings were used to investigate age related differences in periodicity encoding of the temporal envelope and fine structure components of the response to a /da/speech token. A group of younger and a group of older adults (n = 22 per group) participated. The results demonstrated reduced amplitude of the fundamental frequency and harmonic components in the spectral domain of the recorded response of the older listeners. In experiment 2, a model of neural temporal jitter was employed to simulate in a group of young adults (n = 22) the response patterns measured from older adults. A small group of older adults (n = 7) were also tested under the jitter simulation conditions. In the young adults, the results showed a systematic reduction in the response amplitude of the most robust response components as the degree of applied jitter increased. In contrast, the older adults did not demonstrate significant response reduction when tested under jitter conditions. The overall pattern of results suggests that older adults have reduced neural synchrony for encoding periodic, complex signals at the level of the brainstem, and that this reduced synchrony can be modeled by simulating neural jitter via disruption of the temporal waveform of the stimulus. PMID- 26368031 TI - Novel Totally Robotic Repair of Right Ventricular Outflow Tract Obstruction. AB - Right ventricular outflow tract (RVOT) obstruction is among the commonest congenital heart defects in the grown-up, and pulmonary stenosis is the dominant subtype. We described our successful novel surgical technique of totally robotic antegrade RVOT repair in two cases of pulmonary stenosis with concomitant repair of atrial septal defect using da Vinci SI Surgical System (Intuitive Surgical, Inc, Sunnyvale, CA USA) with excellent surgical outcome. We conclude that robotic antegrade repair of the valvular and subvalvular subset of RVOT obstruction is feasible in adults. PMID- 26368032 TI - The "Spacemaker", a New Device for Minimally Invasive Cardiothoracic Surgery: An Evaluation and Feasibility Study. AB - OBJECTIVE: Our aim was to evaluate a new inflatable lung retractor, the "Spacemaker", and its efficacy in facilitating minimally invasive cardiothoracic surgery without the need of one lung ventilation or carbon dioxide overpressure insufflation. METHODS: The device was tested in 12 anesthetized pigs (90-100 kg) placed on standard endotracheal ventilation. The device was introduced into the right or left side of the chest, depending on the intended procedure to be performed, via a 3-cm incision in the fifth intercostal space. A total of seven animals were used to evaluate hemodynamic and respiratory response to the device, whereas another five animals were used to assess the feasibility of a variety of minimally invasive cardiothoracic surgical procedures. RESULTS: Introduction was easy and unhindered. The device was inflated up to 0.6 bar, thereby pushing the lung tissue gently away cranially, posteriorly, and caudally without interfering with pulmonary function or resulting in respiratory compromise. In addition, hemodynamics remained stable throughout the experiments. Different closed-chest surgical procedures such as left atrial appendage exclusion, pulmonary vein exposure, pacemaker lead placement, and endoscopic stabilization for coronary surgery, were successfully performed. Removal was quick and complete in all cases, and lung tissue showed no remnant atelectasis. CONCLUSIONS: The "Spacemaker" may represent a reliable alternative to current conventional techniques to facilitate minimally invasive cardiothoracic surgery. Further research is warranted to confirm the effectiveness and the safety of this device and to optimize the model before its use in humans and its introduction into clinical practice. PMID- 26368033 TI - Use of the Impella 5.0 Device as a Bridge to Recovery in Adult Fulminant Viral Myocarditis. AB - We present a case of a 48-year-old female patient successfully bridged to recovery with the Impella 5.0 microaxial pump (Abiomed, Danvers, MA USA) after presenting with cardiogenic shock secondary to acute fulminant viral myocarditis. After 1 week of flu-like symptoms, the patient presented to her community emergency department with chest pain and hypotension. A diagnosis of inferior ST elevation myocardial infarction was made; subsequent angiography demonstrated normal coronary arteries and a left ventricular ejection fraction of 10%. A provisional diagnosis of viral myocarditis was made. As her condition deteriorated further, she underwent insertion of an Impella 5.0 after failure of supportive medical therapy. Myocardial recovery occurred, and the Impella was removed after 1 week. After a prolonged cardiac intensive care unit stay requiring temporary hemodialysis, the patient recovered sufficiently to tolerate device explant, transfer to the recovery ward, and ultimate discharge home. This case report highlights the benefit of mechanical circulatory support in a patient with cardiogenic shock from viral myocarditis as well as some of the complications that can occur in this critically ill subset of patients. PMID- 26368034 TI - Sutureless Aortic Valve Replacement in the Setting of Triple-Valve Surgery. AB - Sutureless aortic valve replacement is an emerging alternative to standard aortic valve replacement in high-risk surgical patients. We present our surgical technique for sutureless aortic valve replacement in patients undergoing triple valve surgery. This procedure has been performed in six patients with excellent clinical and echocardiographic results. Despite some technical concerns, sutureless aortic valve replacement in the setting of triple-valve surgery is simple and reproducible. PMID- 26368035 TI - Transthoracic Extracorporeal Gastric Conduit Preparation for Minimally Invasive Ivor-Lewis Esophagectomy. AB - OBJECTIVE: During totally minimally invasive esophagectomy (MIE), the gastric conduit is typically constructed via laparoscopy. Trauma from laparoscopic instruments, inability to palpate the gastroepiploic arcade, and challenges in optimal positioning of the stomach for intra-abdominal stapling have led to the widespread use of laparotomy as part of hybrid MIE procedures. Our objective was to evaluate the safety of transthoracic extracorporeal gastric conduit preparation. We hypothesize that this alternative technique is equivalent in safety to the laparoscopic approach. METHODS: This is a retrospective comparison of laparoscopic and transthoracic extracorporeal gastric conduit preparation with regard to anastomotic and respiratory outcomes. RESULTS: During a 3-year period, 30 patients underwent MIE with a right intrathoracic anastomosis (extracorporeal conduit, 15; laparoscopic conduit, 15). Mean age (58.6 vs 67 years, P = 0.59), tumor location (gastroesophageal junction vs middle and lower esophageal, P = 0.27), and histology (adenocarcinoma vs other 26.7%, P = 0.68) were similar between groups. Anastomotic technique and operating surgeon were the same for all patients. Patients in the laparoscopic gastric conduit group were more likely to have undergone induction chemoradiotherapy (40% vs 80%, P = 0.030). There was no significant difference between groups with respect to anastomotic complications, including anastomotic leak and anastomotic stricture (20% vs 13.3%, P = 0.70). Transthoracic gastric conduit preparation was not associated with increased respiratory complications (8% vs 12%, P = 0.09). CONCLUSIONS: Transthoracic gastric conduit preparation is a simple, minimally invasive alternative laparotomy for gastric conduit preparation during MIE. No additional incision is required. The technique may help surgeons overcome shortcomings of the laparoscopic approach without impacting perioperative risk. PMID- 26368036 TI - Early and Midterm Results of No-Touch Aorta Multivessel Small Thoracotomy Coronary Artery Bypass Grafting: A Propensity Score-Matched Study. AB - OBJECTIVE: To carry out the comparative analysis of early and midterm results of no-touch aorta multivessel small thoracotomy coronary artery bypass grafting (MVST CABG), conventional off-pump (OPCABG) and on-pump CABG (ONCABG). METHODS: From 2007 to 2014, 537 consecutive patients underwent CABG by the same surgeon. Propensity score computer matching was performed, and a total of 453 patients were successfully matched in 3 groups of 151 patients. RESULTS: Significant differences were found in the intraoperative blood loss: 220 (180; 300) mL in MVST CABG versus 400 (300; 550) mL in OPCABG vs 350 (250; 435) mL in ONCABG group; first 24-hour postoperative blood loss: 170 (100; 280), 320 (200; 470), and 380 (200; 500) mL, respectively; operation time: 352.4 +/- 74.4, 289.3 +/- 55.0, and 280.4 +/- 56.4 minutes, respectively; median time to return to full physical activity: 14, 56, and 56 days, respectively (P < 0.05); rate of deep wound infection: 0.0%, 2.0%, and 2.0%, respectively; and postoperative length of stay (surgical department): 4.5, 7.0, and 7.5 days, respectively (P < 0.1). No significant differences were observed in rates of severe in-hospital events (P > 0.05), cumulative midterm survival, and freedom from major adverse cardiac and cerebrovascular events (P > 0.05). CONCLUSIONS: The MVST CABG seems as safe as OPCABG and ONCABG and is associated with less wound infections, perioperative blood loss, shorter hospital length of stay and time to return to full physical activity. Multivessel small thoracotomy CABG can be applied to most patients with coronary heart disease saving the effectiveness during midterm follow-up. The MVST CABG can be introduced avoiding a prolonged learning curve. PMID- 26368037 TI - Acidosis and Formaldehyde Secretion as a Possible Pathway of Cancer Pain and Options for Improved Cancer Pain Control. AB - The prevalence of cancer pain in patients with cancer is high. The majority of efforts are spent on research in cancer treatment, but only a small fraction focuses on cancer pain. Pain in cancer patients, viewed predominantly as a secondary issue, is considered to be due to the destruction of tissues, compression of the nerves, inflammation, and secretion of biological mediators from the necrotic tumor mass. As a result, opioid drugs have remained as the primary pharmacological therapy for cancer pain for the past hundred years. This report reviews evidence that cancer pain may be produced by the metabolic effects of two byproducts of cancer-high acidity in the cancer microenvironment and the secretion of formaldehyde and its metabolites. We propose the research and development of therapeutic approaches for preemptive, short- and long-term management of cancer pain using available drugs or nutraceutical agents that can suppress or neutralize lactic acid production in combination with formaldehyde scavengers. We believe this approach may not only improve cancer pain control but may also enhance the quality of life for patients. PMID- 26368038 TI - Diabetes and the female disadvantage. AB - We have produced compelling evidence that women are subject to a higher relative increase in their risk of coronary heart disease and stroke following a diagnosis of Type 2 diabetes. Thus, in terms of vascular risk, diabetes confers a female disadvantage. This excess risk could be due to three main factors. First, it is conceivable that this is merely a mathematical artifact caused by the relatively low background rate for cardiovascular diseases among women, compared with men. Second, it could be due to women receiving poorer care following their diagnosis of diabetes than men; for instance, due to physician bias. Third, certain underlying biological differences in women and men, most likely related to the distribution of body fat, could explain this female disadvantage. PMID- 26368040 TI - Design, synthesis, biological evaluation and molecular docking studies of novel benzofuran-pyrazole derivatives as anticancer agents. AB - This study deals with design and synthesis of novel benzofuran-pyrazole hybrids as anticancer agents. Eight compounds were chosen by National Cancer Institute (NCI), USA to evaluate their in vitro antiproliferative activity at 10(-5)M in full NCI 60 cell panel. The preliminary screening of the tested compounds showed promising broad-spectrum anticancer activity. Compound 4c was further assayed for five dose molar ranges in full NCI 60 cell panel and exhibited remarkable growth inhibitory activity pattern against Leukemia CCRF-CEM, MOLT-4, Lung Cancer HOP 92, Colon Cancer HCC-2998, CNS Cancer SNB-75, Melanoma SK-MEL-2, Ovarian Cancer IGROV1, Renal Cancer 786-0, RXF 393, Breast Cancer HS 578T and T-47D (GI50: 1.00 2.71MUM). Moreover, enzyme assays were carried out to investigate the possible antiproliferative mechanism of action of compound 4c. The results revealed that compound 4c has good c-Src inhibitory activity at 10MUM. In addition, molecular docking studies showed that 4c could bind to the ATP Src pocket sites. Fulfilling the Lipinskiis rule of five in addition to its ADME profile and the biological results, all strongly suggest that 4c is a promising Src kinase inhibitor. PMID- 26368041 TI - Training students to use syringe pumps: an experimental comparison of e-learning and classroom training. AB - The inadequate use of syringe pumps can jeopardize patient safety, and syringe pump trainings are conducted to manage this risk. A critical step in this risk management process is the learning success of trainees. In the present paper, we compared an e-learning approach with standard classroom training in learning success effectives, trainees' opinion on the trainings, and investigated the relation between technological affinity and learning success. The results showed that e-learning was as effective as classroom training but nursing students' confidence in using the pump and satisfaction with the training was decreased for e-learning compared with classroom training. We discuss the results in context of the nursing e-learning literature. Finally, we discuss the literature for risk identification, risk analysis, risk treatment, and risk monitoring and control in the context of syringe pump training and add the lessons learned from the evaluated e-learning program. PMID- 26368042 TI - The implications of non-linear biological oscillations on human electrophysiology for electrohypersensitivity (EHS) and multiple chemical sensitivity (MCS). AB - The 'informational content' of Earth's electromagnetic signaling is like a set of operating instructions for human life. These environmental cues are dynamic and involve exquisitely low inputs (intensities) of critical frequencies with which all life on Earth evolved. Circadian and other temporal biological rhythms depend on these fluctuating electromagnetic inputs to direct gene expression, cell communication and metabolism, neural development, brainwave activity, neural synchrony, a diversity of immune functions, sleep and wake cycles, behavior and cognition. Oscillation is also a universal phenomenon, and biological systems of the heart, brain and gut are dependent on the cooperative actions of cells that function according to principles of non-linear, coupled biological oscillations for their synchrony. They are dependent on exquisitely timed cues from the environment at vanishingly small levels. Altered 'informational content' of environmental cues can swamp natural electromagnetic cues and result in dysregulation of normal biological rhythms that direct growth, development, metabolism and repair mechanisms. Pulsed electromagnetic fields (PEMF) and radiofrequency radiation (RFR) can have the devastating biological effects of disrupting homeostasis and desynchronizing normal biological rhythms that maintain health. Non-linear, weak field biological oscillations govern body electrophysiology, organize cell and tissue functions and maintain organ systems. Artificial bioelectrical interference can give false information (disruptive signaling) sufficient to affect critical pacemaker cells (of the heart, gut and brain) and desynchronize functions of these important cells that orchestrate function and maintain health. Chronic physiological stress undermines homeostasis whether it is chemically induced or electromagnetically induced (or both exposures are simultaneous contributors). This can eventually break down adaptive biological responses critical to health maintenance; and resilience can be compromised. Electrohypersensitivity can be caused by successive assaults on human bioelectrochemical dynamics from exogenous electromagnetic fields (EMF) and RFR or a single acute exposure. Once sensitized, further exposures are widely reported to cause reactivity to lower and lower intensities of EMF/RFR, at which point thousand-fold lower levels can cause adverse health impacts to the electrosensitive person. Electrohypersensitivity (EHS) can be a precursor to, or linked with, multiple chemical sensitivity (MCS) based on reports of individuals who first develop one condition, then rapidly develop the other. Similarity of chemical biomarkers is seen in both conditions [histamines, markers of oxidative stress, auto-antibodies, heat shock protein (HSP), melatonin markers and leakage of the blood-brain barrier]. Low intensity pulsed microwave activation of voltage gated calcium channels (VGCCs) is postulated as a mechanism of action for non thermal health effects. PMID- 26368043 TI - Knowledge and attitude about pubertal health and their socio-demographic predictors in Iranian adolescents. AB - BACKGROUND: Adolescence is a critical period and is associated with physical and psycho-social changes induced by puberty, which builds personality, behavior, and future health of the adolescents. This study aimed to determine the adolescent's knowledge and attitude toward pubertal health and his/her socio-demographic predictors. METHODS: This cross-sectional study was performed on 1017 adolescent girls who were in the second and third grades of secondary schools in Tabriz, Iran, in 2013. The sampling method was random. The general linear model was used to determine the social-demographic predictors of the adolescent's knowledge and attitude about pubertal health. RESULTS: The mean (standard deviation) score of knowledge and attitude was 53.2 (13.7) and 66.7 (11.5), respectively (from an attainable score range of 0-100). The variables of educational level, economic status, household members, obtaining information about the puberty, and age of menarche were predictors of knowledge. Educational level, the most feeling at menarche, and source of the most information about puberty were predictors of attitude (p<0.05). CONCLUSION: The findings of this study show that the knowledge and attitude of adolescents about pubertal health are moderate. Thus, it is necessary to educate the girls about pubertal health to enable them to have a healthy reproductive life in the future. PMID- 26368044 TI - Family functionality and parental characteristics as determinants of sexual decision-making of in-school youths in a semi-urban area of Southwest Nigeria. AB - BACKGROUND: Though research findings have indicated that family characteristics have a bearing on sexual behavior, there is a paucity of published literature on the role of family functionality and parental characteristics on adolescent sexual decision-making. This study was designed to assess the role of family function and parental influence on sexual behavior of in-school youths in secondary schools in a sub-urban area of Southwest Nigeria. METHODS: A descriptive cross-sectional study was conducted among secondary school students using semi-structured interviewer-assisted questionnaire. Information was obtained on the sexual behavior and parent-child characteristics. Family functionality was assessed using family APGAR standardized instrument. Association was established using chi2-test for qualitative variables and t-test for quantitative variables at p=0.05. RESULTS: Mean age of respondents was 14.8+/ 2.2 years. Majority were from monogamous family setting (70.7%) and lived with their families (75.6%). About a quarter (26.8%) was from dysfunctional families and 9.2% had ever had sexual intercourse. Recent sexual engagement in the preceding 1 month was reported (47.4%). The mean score for parental monitoring, father-child communication, mother-child communication, and parental disapproval of sex were 10.4+/-2.2, 9.3+/-2.3, 9.8+/-2.4, and 10.4+/-2.3, respectively. There was a significant association between parental monitoring (t=3.9, p<=0.001), mother-child communication (t=3.03, p=0.003), and parental disapproval of sex (t=5, p<=0.001); and sexual experience. CONCLUSION: This study showed that parental influence had a vital role in the sexual behavior of young persons. Advocacy and health education interventions are needed among parents regarding their role in the sexual behavior of in-school youths. PMID- 26368045 TI - Volatile constituents of Dietes bicolor (Iridaceae) and their antimicrobial activity. AB - Volatile oils from the leaves, flowers and rhizomes of Dietes bicolor (Steud.) Sweet ex Klatt (Iridaceae) were analyzed using GLC/FID and GLC/MS. A total of 84 compounds were identified accounting for 94.65, 95.63 and 87.09% in the hydrodistilled oils from flowers, leaves and rhizomes, respectively. Spathulenol (48.44%) represented the major component in the leaf oil, followed by dihydro edulan I (6.25%), cubenol (6.00%) and tau-cadinol (5.90%). For the flower and rhizome oils, fatty acids, their esters, aliphatic hydrocarbons and their derivatives predominate. The antimicrobial activity of both leaf and flower oils was investigated against four bacteria in addition to four fungi using the micro broth dilution method. The leaf oil showed a more potent antimicrobial activity as compared to the flower oil against most of the assessed bacteria and fungi, with higher activities against Gram- positive organisms showing MIC values of 115 and 460 MUg/ml for Bacillus subtilis and Streptococcus pneumonia, respectively. Gram-negative bacteria were generally less susceptible (MIC > 2 mg/ml for both oils against Escherichia coli) and being completely ineffective against Pseudomonas aeruginosa. A relevant antifungal potency of the leaf oil against Geotrichum candidum and Syncephalastrum racemosum was also observed with MIC values of 115 and 920 MUg/ml, respectively. PMID- 26368046 TI - Strengths and weaknesses of methods for identifying monoclonal free light chains of Ig: examples from two cases with renal disease. AB - BACKGROUND: Serum free light chain (FLC) analysis with ratio and urine immunofixation electrophoresis (IFE) are both available for routine use in helping to detect plasma cell dyscrasia and related diseases. CASES: Case reports showing one serum positive for serum FLC but that showed a hook effect and overestimated the amount of monoclonal FLC while urine IFE was negative for Bence Jones protein, and a second serum that showed elevated FLC kappa and lambda but a normal kappa/lambda ratio, while urine IFE was positive for Bence Jones protein. CONCLUSIONS: These two techniques complement one another. Neither of the techniques is truly quantitative, and both exhibit methodological defects. PMID- 26368047 TI - The complete mitochondrial genome of the flea beetle Agasicles hygrophila. AB - To provide molecular markers for population genetic analysis of the flea beetle Agasicles hygrophila, we determined its mitochondrial genome (mitogenome) for the first time. The mitogenome of A. hygrophila was 15 917 bp in length with an AT content of 75.15%. It had the typical set of 13 protein-coding genes (PCGs), 22 tRNA genes, two rRNA genes, and an AT-rich control region. Compared with the ancestral mitogenome of insects, no gene rearrangement occurred in A. hygrophila. Incomplete stop codons were present in PCGs of A. hygrophila. All tRNA genes except for trnS(AGN) could form the typical clover-leaf secondary structures. The phylogenetic analysis indicated that A. hygrophila was close to other species belonging to the same family of Chrysomelidae. PMID- 26368048 TI - Engineering pulmonary vasculature in decellularized rat and human lungs. AB - Bioengineered lungs produced from patient-derived cells may one day provide an alternative to donor lungs for transplantation therapy. Here we report the regeneration of functional pulmonary vasculature by repopulating the vascular compartment of decellularized rat and human lung scaffolds with human cells, including endothelial and perivascular cells derived from induced pluripotent stem cells. We describe improved methods for delivering cells into the lung scaffold and for maturing newly formed endothelium through co-seeding of endothelial and perivascular cells and a two-phase culture protocol. Using these methods we achieved ~75% endothelial coverage in the rat lung scaffold relative to that of native lung. The regenerated endothelium showed reduced vascular resistance and improved barrier function over the course of in vitro culture and remained patent for 3 days after orthotopic transplantation in rats. Finally, we scaled our approach to the human lung lobe and achieved efficient cell delivery, maintenance of cell viability and establishment of perfusable vascular lumens. PMID- 26368049 TI - Detection of low-abundance bacterial strains in metagenomic datasets by eigengenome partitioning. AB - Analyses of metagenomic datasets that are sequenced to a depth of billions or trillions of bases can uncover hundreds of microbial genomes, but naive assembly of these data is computationally intensive, requiring hundreds of gigabytes to terabytes of RAM. We present latent strain analysis (LSA), a scalable, de novo pre-assembly method that separates reads into biologically informed partitions and thereby enables assembly of individual genomes. LSA is implemented with a streaming calculation of unobserved variables that we call eigengenomes. Eigengenomes reflect covariance in the abundance of short, fixed-length sequences, or k-mers. As the abundance of each genome in a sample is reflected in the abundance of each k-mer in that genome, eigengenome analysis can be used to partition reads from different genomes. This partitioning can be done in fixed memory using tens of gigabytes of RAM, which makes assembly and downstream analyses of terabytes of data feasible on commodity hardware. Using LSA, we assemble partial and near-complete genomes of bacterial taxa present at relative abundances as low as 0.00001%. We also show that LSA is sensitive enough to separate reads from several strains of the same species. PMID- 26368050 TI - Optogenetic control of endogenous Ca(2+) channels in vivo. AB - Calcium (Ca(2+)) signals that are precisely modulated in space and time mediate a myriad of cellular processes, including contraction, excitation, growth, differentiation and apoptosis. However, study of Ca(2+) responses has been hampered by technological limitations of existing Ca(2+)-modulating tools. Here we present OptoSTIM1, an optogenetic tool for manipulating intracellular Ca(2+) levels through activation of Ca(2+)-selective endogenous Ca(2+) release-activated Ca(2+) (CRAC) channels. Using OptoSTIM1, which combines a plant photoreceptor and the CRAC channel regulator STIM1 (ref. 4), we quantitatively and qualitatively controlled intracellular Ca(2+) levels in various biological systems, including zebrafish embryos and human embryonic stem cells. We demonstrate that activating OptoSTIM1 in the CA1 hippocampal region of mice selectively reinforced contextual memory formation. The broad utility of OptoSTIM1 will expand our mechanistic understanding of numerous Ca(2+)-associated processes and facilitate screening for drug candidates that antagonize Ca(2+) signals. PMID- 26368051 TI - Factors affecting progression-free survival in non-HIV-related Kaposi sarcoma. AB - BACKGROUND: Non-HIV related Kaposi sarcoma (NHKS) is a rare indolent neoplasm which is more common around Mediterranean origin. Data concerning factors that influence progression-free survival (PFS) for NHKS are insufficient. The purpose of present retrospective analysis was to distinguish the factors affecting PFS in patients with NHKS. METHODS: A hundred and twenty-eight consecutive patients with NHKS who were treated or observed between 1997 and 2014 at Istanbul University Institute of Oncology were included into the study. Treatment response and progression definitions were determined according to different treatment modalities administered at first line. RESULTS: Majority of patients were male (n = 97, 75.8%). Median age of the whole group was 66 years (28-85). Of the patients, 15 patients were immunosuppressant, whereas 113 patients had no disease that caused immunosuppression. Patients were treated with local excision (n = 57, 44.5%), chemotherapy (n = 32, 25.0%) and/or radiotherapy (n = 13, 10.2%) or observed without treatment (n = 26, 20.3%). At a median follow-up of 28 months, 71 (55.5%) patients had progression, while 3 patients (2.3%) died of NHKS. On univariate analysis, patients who had hypertension (HT) had poorer PFS compared with others (19 +/- 12 versus 41 +/- 22 months; p = 0.03), whereas plaque formation was associated with better outcome (25 +/- 9 versus 54 +/- 12 months; p = 0.03). In addition, heavy smoking (>=40 pack-years) had a borderline significance regarding better PFS time (23 +/- 24 versus 45 +/- 38 months, p = 0.06). On multivariate analysis, none of factors evaluated had any impact on PFS. CONCLUSIONS: HT was correlated with poorer outcome among NHKS patients. Patients with plaque formation and >=40 pack-years of smoking had better PFS than others. PMID- 26368053 TI - Immunogenicity and efficacy in mice of an adenovirus-based bicistronic rotavirus vaccine expressing NSP4 and VP7. AB - NSP4 and VP7 are important functional proteins of rotavirus. Proper combination of viral gene expression is favorable to improving the protection effect of subunit vaccine. In the present study, We evaluated the immunogenicity and efficacy of the bicistronic recombinant adenovirus (rAd-NSP4-VP7) and two single gene expressing adenoviruses (rAd-NSP4, rAd-VP7). The three adenovirus vaccines were used to immunize mice by intramuscular or intranasal administration. The data showed significant increases in serum antibodies, T lymphocyte subpopulations proliferation, and cytokine secretions of splenocyte in all immunized groups. However, the serum IgA and neutralizing antibody levels of the rAd-NSP4-VP7 or rAd-VP7 groups were significantly higher than those of the rAd NSP4, while the splenocyte numbers of IFN-gamma secretion in the rAd-NSP4-VP7 or rAd-NSP4 groups was greater than that of the rAd-VP7. Furthermore, the efficacy evaluation in a suckling mice model indicated that only rAd-NSP4-VP7 conferred significant protection against rotavirus shedding challenge. These results suggest that the co-expression of NSP4 and VP7 in an adenovirus vector induce both humoral and cell-mediated immune responses efficiently, and provide potential efficacy for protection against rotavirus disease. It is possible to represent an efficacious subunits vaccine strategy for control of rotavirus infection and transmission. PMID- 26368054 TI - TFEB Participates in the Abeta-Induced Pathogenesis of Alzheimer's Disease by Regulating the Autophagy-Lysosome Pathway. AB - To investigate whether transcriptional factor EB (TFEB) participates in amyloid beta(1-42) (Abeta(1-42))-induced pathogenesis of Alzheimer's disease (AD) and its underlying mechanisms. Three-month-old and 8-month-old transgenic APP/PS1 AD mice and age-matched wild mice were used in this study. We found that the 8-month-old AD animals presented significantly higher deposition of Abeta(1-42) and expression of TFEB and its targeted proteins, such as LAMP-1 and cathepsin D, and autophagy-associated LC3-II and p62 in brain tissues than in others. In an in vitro study, TFEB overexpression rescued autophagic flux that blocked by Abeta(1 42) and the degradation of the absorbed Abeta(1-42), relieved Abeta(1-42) mediated induction of overloaded autophagy. In addition, TFEB overexpression enhanced cathepsin D expression and activity, restored Abeta(1-42)-disturbed acid environment of lysosome, and promoted the fusion of autophagosomes with lysosomes. Furthermore, TFEB upregulation reduced Abeta(1-42)-induced production of malondialdehyde, oxidative carbonyl proteins, and reactive oxygen species (ROS) and cell apoptosis mainly dependent on the removal of Abeta(1-42) by the autophagy-lysosome pathway. TFEB overexpression alleviated AD progression by reducing Abeta accumulation through regulating the autophagy-lysosome pathway and reducing Abeta-induced ROS production and cell apoptosis. PMID- 26368052 TI - Standing your ground to exoribonucleases: Function of Flavivirus long non-coding RNAs. AB - Members of the Flaviviridae (e.g., Dengue virus, West Nile virus, and Hepatitis C virus) contain a positive-sense RNA genome that encodes a large polyprotein. It is now also clear most if not all of these viruses also produce an abundant subgenomic long non-coding RNA. These non-coding RNAs, which are called subgenomic flavivirus RNAs (sfRNAs) or Xrn1-resistant RNAs (xrRNAs), are stable decay intermediates generated from the viral genomic RNA through the stalling of the cellular exoribonuclease Xrn1 at highly structured regions. Several functions of these flavivirus long non-coding RNAs have been revealed in recent years. The generation of these sfRNAs/xrRNAs from viral transcripts results in the repression of Xrn1 and the dysregulation of cellular mRNA stability. The abundant sfRNAs also serve directly as a decoy for important cellular protein regulators of the interferon and RNA interference antiviral pathways. Thus the generation of long non-coding RNAs from flaviviruses, hepaciviruses and pestiviruses likely disrupts aspects of innate immunity and may directly contribute to viral replication, cytopathology and pathogenesis. PMID- 26368055 TI - ATG5-knockout mutants of Physcomitrella provide a platform for analyzing the involvement of autophagy in senescence processes in plant cells. AB - Autophagy is a pathway in which a cell degrades part of its cytoplasm in vacuoles or lysosomes. To identify the physiological functions of autophagy in plants, we disrupted ATG5, an autophagy-related gene, in Physcomitrella, and confirmed that atg5 mutants are deficient in the process of autophagy. On carbon or nitrogen starvation medium, atg5 colonies turned yellow earlier than the wild-type (WT) colonies, showing that Physcomitrella atg5 mutants, like yeast and Arabidopsis, are sensitive to nutrient starvation. In the dark, even under nutrient-sufficient conditions, colonies turned yellow and the net degradation of chlorophyll and Rubisco protein occurred together with the upregulation of several senescence associated genes. Yellowing reactions were inhibited by the protein synthesis inhibitor cycloheximide, suggesting that protonemal colonies undergo dark-induced senescence like the green leaves of higher plants. Such senescence responses in the dark occurred earlier in atg5 colonies than WT colonies. The sugar content was almost the same between WT and atg5 colonies, indicating that the early senescence phenotype of atg5 is not explained by sugar deficiency. However, the levels of 7 amino acids showed significantly different alteration between atg5 and WT in the dark: 6 amino acids, particularly arginine and alanine, were much more deficient in the atg5 mutants, irrespective of the early degradation of Rubisco protein. On nutrient-sufficient medium supplemented with casamino acids, the early-senescence phenotype was slightly moderated. We propose that the early senescence phenotype in atg5 mutants is partly explained by amino acid imbalance because of the lack of cytoplasmic degradation by autophagy in Physcomitrella. PMID- 26368056 TI - Analysis of the Transperitoneal Approach to Robot-Assisted Laparoscopic Partial Nephrectomy for the Treatment of Anterior and Posterior Renal Masses. AB - OBJECTIVE: Few studies have directly assessed the impact of tumor anterior/posterior location during transperitoneal robotic-assisted laparoscopic partial nephrectomy (TPRPN). The present study sought to assess perioperative and pathological outcomes associated with TPRPN among patients with anterior versus posterior tumors. PATIENTS AND METHODS: The Institutional Review Board-approved Mount Sinai Kidney Cancer database was used to identify 123 patients who underwent TPRPN from May 2011 to April 2015. Perioperative outcomes, including operative time, warm ischemia time (WIT), estimated blood loss (EBL), hospital length of stay (LOS), surgical margin status, complications, and reduction in estimated glomerular filtration rate (eGFR) at discharge and at last follow-up, were compared between those with anterior and posterior masses while controlling for clinical and pathological variables (i.e., age, gender, body mass index, tumor size, tumor laterality, malignancy, hilar location, and R.E.N.A.L. nephrometry score). RESULTS: Clinical and pathological characteristics were comparable between groups; mean tumor size was 3.1 cm anterior versus 2.8 cm posterior (P = .187). Tumor complexity (i.e., nephrometry scores, 6.9 versus 6.3; P = .097) and proportion of malignancy (74.5% versus 73.1%; P = .799) were also similar between posterior and anterior masses. In multivariable analyses, perioperative outcomes, including operative time, WIT, EBL, LOS, surgical margin status, reduction in eGFR, and postoperative complication rates, did not significantly differ between groups. CONCLUSIONS: The transperitoneal approach to partial nephrectomy for posterior tumors resulted in no difference in operative time, WIT, EBL, LOS, positive surgical margins, reduction in eGFR, or postoperative complications. The TPRPN approach to treat a posterior tumor is reasonable and is the preferred technique at our institution. PMID- 26368057 TI - Management of Children with Travel-related Illness Evaluated in a Pediatric Emergency Room. AB - BACKGROUND: Children travelling are potentially exposed to a wide spectrum of illness, which includes not only mild self-limiting disease but also severe illness requiring hospitalization. Risk factors for hospitalization need to be analyzed to inform prevention and treatment strategies for travel-related disease, to make travelling for children-from a medical perspective-more secure. METHODS: We performed a cross-sectional analysis on children with travel-related disease presenting at the Emergency Room of University of Zurich Children's Hospital between July 2007 and December 2012. The profile of children being hospitalized was compared with that of children treated as outpatients. RESULTS: Eight hundred and one children (57.4% male) were included in the study. Eighty three children (10.4%) were treated as inpatients. Compared with outpatients, inpatients were significantly more likely to be male, to have travelled to Southern Asia, to have a diagnosis of Salmonella typhi or Salmonella paratyphi (3.6 % vs. 0.1%, P < 0.0001), pyogenic abscess (3.6% vs. 0.1 %, P < 0.0001) or malaria (1.4 % vs. 0.2%, P = 0.0384). Neurologic diagnoses (such as seizure disorder: 3.6% vs. 0.4%, P < 0.0001) were diagnosed more often among inpatients. Furthermore, inpatients presented more often with nonspecific findings such as dehydration (8.5% vs. 0.6%, P < 0.0001). No correlation with inpatient care was seen for visiting friends and relatives/immigrant travel. CONCLUSIONS: Children acquire a wide spectrum of travel-related illness. A careful, detailed travel history is important in children presenting in the emergency room with symptoms suggesting infectious disease. PMID- 26368059 TI - Early-onset Sepsis and Antibiotic Exposure in Term Infants: A Nationwide Population-based Study in Norway. AB - BACKGROUND: Sepsis is a leading cause of neonatal morbidity and mortality. Clinical suspicion may lead to overuse of antibiotics. The objective of this study was to assess the epidemiology of early-onset sepsis (EOS) and antibiotic exposure during the first week of life in Norwegian term infants. METHODS: This is a nationwide population-based study from the Norwegian Neonatal Network. During the 3-year study period (2009-2011), 20 of Norway's 21 neonatal units prospectively collected data. Among 168,877 live-born (LB) term infants born during the study period, 10,175 (6.0%) infants were hospitalized in the first week of life and included in the study. RESULTS: There were 91 cases of culture confirmed EOS (0.54 per 1000 LB) and 1447 cases classified as culture-negative EOS (8.57 per 1000 LB). The majority of culture-confirmed EOS cases were caused by Gram-positives (83/91; 91%), most commonly group B streptococci (0.31 per 1000 LB). Intravenous antibiotics were administered to 3964 infants; 39% of all admissions and 2.3% of all LB term infants. Empiric therapy consisted of an aminoglycoside and either benzylpenicillin or ampicillin in 95% of the cases. The median (interquartile range) treatment duration was 8 (7-10) days for culture confirmed EOS and 6 (5-7) days for culture-negative EOS. There was 1 EOS attributable death (group B streptococcal EOS) during the study period. CONCLUSIONS: In this registry-based study, the incidence of culture-confirmed EOS was in line with previous international reports and the mortality was very low. A large proportion of infants without infection were treated with antibiotics. Measures should be taken to spare neonates unnecessary antibiotic treatment. PMID- 26368058 TI - Seroprevalence of Enterovirus 71 Antibody Among Children in China: A Systematic Review and Meta-analysis. AB - BACKGROUND: Hand, foot and mouth disease mostly affects children and carries a substantial disease burden in the Western Pacific region. Enterovirus 71 (EV71) is the most virulent causative agent, and a monovalent vaccine against EV71 will soon become commercially available in China. An improved understanding of EV71 epidemiology would aid policy decisions regarding childhood immunization in China. We aimed to assess and summarize information to date from individual seroepidemiologic studies of EV71 in mainland China to determine patterns of the age-specific risk of infection. METHODS: A systematic review and meta-analysis of studies of children aged 0-15 years, published in English or Chinese, was conducted. Estimates of seroprevalence were summarized by age group. A mixed effects regression model was used to explore factors covarying with EV71 seroprevalence. RESULTS: We identified 42 published studies, 15 in English. We found that an average of 78% of neonates was seropositive to EV71 infection, but such maternally conferred immunity almost completely waned by 5 months. The seroprevalence of EV71 antibody increased directly with age among preschool children, from 26% (95% confidence interval: 18%-33%) at 1 year to 70% (95% confidence interval: 62%-78%) at 5 years. Age of subjects, sample size, sampling year, sampling method, geographic latitude and publication language were associated with variations of individual seroprevalence estimates. CONCLUSIONS: Seroprevalence of EV71 antibody gradually declined during the first 5 months in infants. Infection of EV71 was most likely to occur between 2 and 4 years. Our findings may be useful in informing population-based EV71 vaccination strategies. PMID- 26368060 TI - Improving the managed introduction of new medicines: sharing experiences to aid authorities across Europe. PMID- 26368061 TI - Unique synthesis of hollow Co3O4 nanoparticles embedded in thin Al2O3 nanosheets for enhanced lithium storage. AB - The designed synthesis of advanced nanocomposite architecture is significant for its applications in energy storage, catalysis, sensing, etc. Herein, thin Al2O3 hexagonal nanosheets with encapsulated hollow Co3O4 nanoparticles (Co3O4-HNPs) are successfully synthesized by using Co6Al2CO3(OH)16.4H2O nanosheets as templates followed by a two-step annealing process. When used as an anode material in lithium ion batteries (LIBs), the homogeneous Co3O4-HNP/Al2O3 nanosheet composite exhibits an excellent performance with high reversible capacity and rate capability, and enhanced cycling stability. PMID- 26368062 TI - Diarrhea With Clostridium difficile-Positive Stool-Trick or Treat: A Teachable Moment. PMID- 26368065 TI - Helikaurolides A-D with a Diterpene-Sesquiterpene Skeleton from Supercritical Fluid Extracts of Helianthus annuus L. var. Arianna. AB - Four novel compounds (1-4) with an unprecedented skeleton that combines a sesquiterpene lactone and a kaurane diterpene acid were isolated from Helianthus annuus L. var. Arianna extract, which was obtained under supercritical conditions. The structures of 1-4 were elucidated by NMR and MS analyses. The biosynthetic routes involve sesquiterpene lactones and kauranic acid, both of which were previously isolated from this species. PMID- 26368063 TI - Resting-state functional connectivity and presynaptic monoamine signaling in Alcohol Dependence. AB - Alcohol Dependence (AD) is a chronic relapsing disorder with high degrees of morbidity and mortality. While multiple neurotransmitter systems are involved in the complex symptomatology of AD, monoamine dysregulation and subsequent neuroadaptations have been long postulated to play an important role. Presynaptic monoamine transporters, such as the vesicular monoamine transporter 1 (VMAT1), are likely critical as they represent a key common entry point for monoamine regulation and may represent a shared pathway for susceptibility to AD. Excessive monoaminergic signaling as mediated by genetic variation in VMAT1 might affect functional brain connectivity in particular in alcoholics compared to controls. We conducted resting-state fMRI functional connectivity (FC) analysis using the independent component analysis (ICA) approach in 68 AD subjects and 72 controls. All subjects were genotyped for the Thr136Ile (rs1390938) variant in VMAT1. Functional connectivity analyses showed a significant increase of resting-state FC in 4 networks in alcoholics compared to controls (P < 0.05, corrected). The FC was significantly positively correlated with Alcohol Dependence Scale (ADS). The hyperfunction allele 136Ile was associated with a significantly decreased FC in the Default Mode Network, Prefrontal Cortex Network, and Executive Control Network in alcohol dependent participants (P < 0.05, corrected), but not in controls. Our data suggest that increased FC might represent a neuroadaptive mechanism relevant to AD that is furthermore mediated by genetic variation in VMAT1. The hyperfunction allele Thr136Ile might have a protective effect that is, in particular, relevant in AD by mechanism of increased monoamine transport into presynaptic storage vesicles. PMID- 26368066 TI - Transcatheter arterial chemoembolization (TACE) for lymph node metastases in patients with hepatocellular carcinoma. AB - OBJECTIVE: To evaluate the efficacy and safety of transcatheter arterial chemoembolization (TACE) in hepatocellular carcinoma (HCC) with regional lymph node metastases. METHODS: Forty-eight patients with HCC and regional lymph node metastases were enrolled in this study. The patients were allocated into two groups: Group A (28 patients) underwent TACE for both intrahepatic tumors and lymph node metastasis and Group B (20 patients) received TACE for intrahepatic tumors only. RESULTS: The patients were followed-up by contrast enhanced CT scan 6-8 weeks after TACE treatment. In Group A, seven and nine patients achieved complete and partial response for lymph node metastasis, respectively, with 1 year and 2-year overall survival rates of 60.7% and 35.7%, respectively. In contrast, none of the patients in Group B achieved a complete response, whereas four patients achieved a partial response. The 1-year and 2-year survival rates for the patients in Group B were 40% and 0%, respectively. The difference in survival between the two groups was statistically significant (P = 0.001). CONCLUSIONS: TACE is an effective treatment to regional lymph node metastasis in HCC without significant side effects and could provide survival benefits to the patients with advanced HCC. PMID- 26368067 TI - Control of molecular rotor rotational frequencies in porous coordination polymers using a solid-solution approach. AB - Rational design to control the dynamics of molecular rotors in crystalline solids is of interest because it offers advanced materials with precisely tuned functionality. Herein, we describe the control of the rotational frequency of rotors in flexible porous coordination polymers (PCPs) using a solid-solution approach. Solid-solutions of the flexible PCPs [{Zn(5-nitroisophthalate)x(5 methoxyisophthalate)1-x(deuterated 4,4'-bipyridyl)}(DMF.MeOH)]n allow continuous modulation of cell volume by changing the solid-solution ratio x. Variation of the isostructures provides continuous changes in the local environment around the molecular rotors (pyridyl rings of the 4,4'-bipyridyl group), leading to the control of the rotational frequency without the need to vary the temperature. PMID- 26368068 TI - Thiols-Induced Rapid Photoluminescent Enhancement of Glutathione-Capped Gold Nanoparticles for Intracellular Thiols Imaging Applications. AB - The rapid detection and imaging of intracellular thiols is of great importance during the occurrence and development of some chronic diseases. Here we demonstrate the rapid thiols-induced photoluminescence (PL) enhancement of the low luminescent glutathione (GSH) stabilized Au nanoparticles, AuGSH (low). The dynamic PL investigation reveals that the PL enhancement fits a first-order reaction model. The X-ray photoelectron spectroscopic and mass spectroscopic results indicate that AuGSH (low) are mainly comprised of "thiols-insufficient" Au species and the additional thiols can efficiently attach to the "unsaturated" surface of Au nanoparticles, accompanied by significant PL enhancement. The noncytotoxic AuGSH (low) probe can be successfully applied for imaging of intracellular thiols. Generally, this work illustrates the great prospects of facile-prepared AuGSH (low) as a candidate for thiols labeling and imaging. PMID- 26368071 TI - Intensity distribution of the parhelic circle and embedded parhelia at zero solar elevation: theory and experiments. AB - We describe the individual contributions to the intensity distribution of the parhelic circle for plate-oriented hexagonal crystals at exactly zero solar elevation using geometrical optics. An experimental as well as theoretical study of in-plane ray paths provides details on the mechanism for several halos, including the parhelia, the 120 degrees and 90 degrees parhelia, a blue edge, and the Liljequist parhelia. Azimuthal coordinates for associated characteristic features in the intensity distribution are compared with experimental data obtained using a spinning hexagonal glass prism. PMID- 26368069 TI - Donor site morbidity following DIEP flap for breast reconstruction in Asian patients: Is it different? AB - BACKGROUND: Despite the decrease in donor-site morbidity with the advent of deep inferior epigastric artery perforator (DIEP) flap breast reconstruction, abdominal complications still occur. There have been few studies on donor morbidity considering the ethnic differences in the Asian population, as represented by a lower BMI with less redundant tissue and a tendency for poor scarring. In the present study, the authors investigated the incidence of abdominal complications and their risk factors following DIEP flap breast reconstruction in an Asian population. PATIENTS AND METHODS: The authors conducted a retrospective review of DIEP flap based breast reconstructions performed in the past 5 years. Data regarding patient demographics, surgical details, and abdominal complications were collected from our prospectively maintained database and analyzed. RESULTS: A total of 217 patients who underwent DIEP flap breast reconstruction were included. There were 51 abdominal complications (23.5%), including 18 delayed wound healing, 17 hypertrophic scarring, 12 seroma formation, and 8 abdominal bulges with no hernias. Secondary procedures were performed for the donor-site complications in 36 cases. Flap height was a significant risk factor for overall donor-site morbidity. Harvesting a bipedicle flap was significantly associated with abdominal fat necrosis and hypertrophic scarring. Harvesting a flap based on perforators from both rows was significantly associated with abdominal delayed wound healing and hypertrophic scarring. CONCLUSIONS: DIEP flap breast reconstruction performed in Asian patients showed acceptable donor-site morbidity without significant complications. This study suggests that donor-site morbidity from harvesting a DIEP flap is comparable to that described in Western literatures. PMID- 26368072 TI - Dual-wavelength narrow-linewidth linearly polarized seed source and stimulated Brillouin scattering suppression in its high-power fiber amplification. AB - In this paper, we demonstrate a dual-wavelength narrow-linewidth linearly polarized all-fiber amplifier emitting 1035 and 1030 nm wavelengths with a high power of 80.0 W. The seed source features two sets of fiber Bragg gratings fabricated on polarization maintaining fibers and a ytterbium-doped fiber as the gain medium. Two wavelengths propagate in one overlapping cavity and the power ratio can be tuned by a coiling fiber setup. A master oscillator power amplifier system consisting of a two-stage amplifier is employed. Longitudinally varied strains are applied on the gain fiber to suppress the back-scattered Stokes light in the main amplifier stage. With an appropriate seed power ratio, we are able to generate amplification power to 80.0 W comprised of 1035 and 1030 nm light while achieving an increase of at least six times that of the stimulated Brillouin scattering threshold. Since both frequencies are propagating in one cavity and amplified in one gain medium, the 1035 and 1030 nm lasers have good temporal and spatial overlapping characteristics. This high-power MHz-level linearly polarized structure affords a compact, novel, and high-efficiency approach to different frequency generation of mid-infrared or terahertz emission. PMID- 26368073 TI - Experimental assessment of SU-8 optical waveguides buried in plastic substrate for optical interconnections. AB - Multimode polymer waveguides have been developed to create low-cost, high-speed on-board optical interconnects. Buried optical waveguides made from SU-8 in a polymethyl methacrylate polymer (PMMA) substrate covered with a thin PMMA sheet are a low-cost option for electro-optical interconnects. The propagation losses for a 600 MUm*600 MUm straight waveguide were 1.96, 1.32, and 1.39 dB/cm, respectively, at three different wavelengths (850, 1310, and 1550 nm). The bending loss for a 15 mm bending radius is as high as 6 dB/cm. Transition and radiation losses dominate overall loss when the bending radius is less than 30 mm. The waveguide was excited using a multimode 850 nm VCSEL transmitter and detected using butt-coupled and lens-coupled receivers. The coupling loss was about 1 dB for the butt-coupling technique and 2 dB for lens coupling. The response bandwidth and the group delay of direct modulated (IF) signal were independent of the channel waveguide for communication speeds up to more than 3 GHz. This technique is viable for low-cost, short-length buried optical waveguides. PMID- 26368074 TI - Visualization of the influence of the air conditioning system to the high-power laser beam quality with the modulation coherent imaging method. AB - Air conditioning systems can lead to dynamic phase change in the laser beams of high-power laser facilities for the inertial confinement fusion, and this kind of phase change cannot be measured by most of the commonly employed Hartmann wavefront sensor or interferometry due to some uncontrollable factors, such as too large laser beam diameters and the limited space of the facility. It is demonstrated that this problem can be solved using a scheme based on modulation coherent imaging, and thus the influence of the air conditioning system on the performance of the high-power facility can be evaluated directly. PMID- 26368075 TI - Numerical simulations of holographic spatiospectral traces of spatiotemporally distorted ultrashort laser pulses. AB - We simulate traces for a catalog of spatiotemporally complex pulses measured using a single-shot complete spatiotemporal pulse-measurement technique we recently developed, called Spatially and Temporally Resolved Intensity and Phase Evaluation Device: Full Information from a Single Hologram (STRIPED FISH). The only such technique ever developed to our knowledge, STRIPED FISH measures the complete spatiotemporal intensity I(x,y,t) and phase phi(x,y,t) of an arbitrary laser pulse using an experimentally recorded trace consisting of multiple digital holograms, one for each frequency present in the pulse. To understand the effects of various spatiotemporal distortions on the STRIPED FISH trace, we numerically investigate STRIPED FISH trace features for a catalog of pulses, including the spatially and temporally transform-limited pulse, temporal and spatial double pulses, spherically focusing and diverging pulses, self-phase modulated and self focusing pulses, spatiotemporally coupled pulses, and pulses with complex structures. As a practical example, we also analyze an experimentally recorded trace of a focusing pulse with spatial chirp. Overall, we find that, from STRIPED FISH's informative trace, significant spatiotemporal characteristics of the unknown pulse can be immediately recognized from the camera frame. This, coupled with its simple pulse-retrieval algorithm, makes STRIPED FISH an excellent technique for measuring and monitoring ultrafast laser sources. PMID- 26368076 TI - Better 3D inspection with structured illumination: signal formation and precision. AB - 3D metrology faces increasing demands for higher precision and larger space bandwidth-speed product (number of 3D points/s). In this paper we consider structured-illumination microscopy as a means for satisfying these demands, developing a theoretical model of the signal formation for both optically smooth and optically rough surfaces. The model allows us to investigate physical limits on precision and to establish rules that allow sensor parameter optimization for greatest precision or highest speed. PMID- 26368077 TI - Determining optical path difference with a frequency-modulated continuous-wave method. AB - A technique for determining the optical path difference (OPD) between two Raman beams using a frequency-modulated continuous-wave method is investigated. This approach greatly facilitates the measurement and adjustment of the OPD when tuning the OPD is essential to minimize the effects of the diode laser's phase noise on Raman lasers. As a demonstration, the frequencies of the beat note with different OPDs are characterized and analyzed. When the measured beat frequency is 0.367 Hz, the OPD between Raman beams is zero. The phase noise of the Raman laser system after implementation of zeroing of the OPD is also measured. PMID- 26368078 TI - Optical study of diffraction grating/Fresnel lens combinations applied to a spectral-splitting solar concentrator for space applications. AB - This paper presents a new design of a planar solar concentrator with spectral splitting of light for space applications. This concentrator spectrally splits the incident light into mainly two parts. Each part is then focused onto specific spatially separated photovoltaic cells allowing for independent control of respective cells' output power. These advantages of both spectral splitting and light focusing are combined here because of a specific diffraction grating superimposed on a Fresnel lens. The theoretical principle of the optical design is presented with optimization of each element and improvement steps including optimization of grating period evolution along the lens and testing of two kinds of gratings (a blazed and a lamellar one). First numerical results are presented highlighting the possibility to design a concentrator at about 10* or more for each cell with an output power larger than that of a classical concentrator focusing on a GaAs single junction cell and less than 10% of losses for tracking errors up to +/-0.8 degrees . Some experimental results are also presented. PMID- 26368079 TI - Effect of charged-particle surface excitations on near-field optics. AB - The mechanism of charge on the near-field intensity distribution is revealed for metallic and dielectric particles with sizes ranging from 10 nm to 10 MUm. The theoretical foundation of near-field intensity perturbations is in the discontinuity of the tangential components of the magnetic fields on either side of the interface between the particle and its surrounding medium, since excess electrons form a thin metal-like layer with elevated conductivity. We have shown that the local fields alter marginally if charges are imposed on a surface of a metallic particle. But an intensity amplification is identified in the vicinity of charged dielectric particles with sizes smaller than the wavelength. Specifically, we have demonstrated that the electromagnetic field is amplified near the poles of the particle as a result of the oriented electric and incident fields. In contrast, a dielectric particle that is large compared to the wavelength becomes opaque with a deep shadow at the side opposite to the beam incidence. As a result, intensity damping is identified near a charged sphere in the geometric optics regime. At significant charge densities, the physical properties of a conductive layer play a dominant role in forming the 3D intensity distribution independent of conductivity or permittivity of the particle core. These findings suggest that some electrically chargeable particles have the potential to be used as optical devices with properties tunable through their net surface charge. PMID- 26368080 TI - Interspacecraft link simulator for the laser ranging interferometer onboard GRACE Follow-On. AB - Link acquisition strategies are key aspects for interspacecraft laser interferometers. We present an optical fiber-based setup able to simulate the interspacecraft link for the laser ranging interferometer (LRI) on gravity recovery and climate experiment Follow-On. It allows one to accurately recreate the far-field intensity profile depending on the mispointing between the spacecraft, Doppler shifts, and spacecraft attitude jitter. Furthermore, it can be used in late integration stages of the mission, since no physical contact with the spacecraft is required. The setup can also be easily adapted to other similar missions and different acquisition algorithms. PMID- 26368081 TI - Divergence of optical vortex beams. AB - We show, both theoretically and experimentally, that the propagation of optical vortices in free space can be analyzed by using the width [w(z)] of the host Gaussian beam and the inner and outer radii of the vortex beam at the source plane (z=0) as defined in [Opt. Lett.39, 4364 (2014)10.1364/OL.39.004364OPLEDP0146-9592]. We also studied the divergence of vortex beams, considered as the rate of change of inner or outer radius with the propagation distance (z), and found that it varies with the order in the same way as that of the inner and outer radii at z=0. These results may be useful in designing optical fibers for orbital angular momentum modes that play a crucial role in quantum communication. PMID- 26368082 TI - Graphene Q-switched eye-safe Nd:Y(3)A(l5)O(12) ceramic dual-wavelength laser. AB - With graphene as a saturable absorber, the efficient and stable 1.4 MUm dual wavelength operation of Nd:YAG ceramic laser is demonstrated. A maximum total average output power of 601 mW is obtained under the pump power of 22.3 W, corresponding to an optical-optical conversion efficiency of 2.7%. The minimum pulse width and the highest pulse repetition rate are 470 ns and 101 kHz, respectively. PMID- 26368083 TI - Dynamic point shifting with null screens using three LCDs as targets for corneal topography. AB - In this paper, the use of three liquid crystal displays (LCDs) as targets for an experimental corneal topographer is proposed. The main advantage is that the geometrical pattern in the target can be modified without moving any mechanical part to apply the dynamic point shifting (DyPoS) method. Some results on the capabilities of the LCDs, obtained with photo frames, for measuring a 6.37 mm radius of curvature calibration sphere, and applying the DyPoS method, are presented. It is shown that the error in measuring the radius of curvature with DyPoS is reduced to 3% of the real value and the RMS in elevation or sagitta differences is around 15 MUm, 30% or 66% of the values obtained without DyPoS, respectively. PMID- 26368084 TI - Generation of dual-wavelength square pulse in a figure-eight erbium-doped fiber laser with ultra-large net-anomalous dispersion. AB - A type of wave-breaking-free mode-locked dual-wavelength square pulse was experimentally observed in a figure-eight erbium-doped fiber laser with ultra large net-anomalous dispersion. A 2.7 km long single-mode fiber (SMF) was incorporated as a nonlinear optical loop mirror (NOLM) and provided largely nonlinear phase accumulation and anomalous dispersion, which enhanced the four wave-mixing effect to improve the stability of the dual-wavelength operation. In the NOLM, the long SMF with small birefringence supported the Sagnac interference as a filter to manage the dual-wavelength lasing. The dual-wavelength operation was made switchable by adjusting the intra-cavity polarization loss and phase delay corresponding to two square pulses. When the pump power was increased, the duration of the square pulse increased continuously while the peak pulse power gradually decreased. This square-type pulse can potentially be utilized for signal transmission and sensing. PMID- 26368085 TI - Automatic 3D object localization and isolation using computational integral imaging. AB - Detecting objects in three-dimensional (3D) space may be useful for various applications. We present a method to detect the 3D locations of objects using computationally reconstructed images obtained by integral imaging. The new algorithm exploits the space-variant blurring properties of the reconstructed images to detect and isolate objects at their depth locations, while removing traces of objects from other depths. With regard to previous work, the proposed method is more efficient and more resistant to noise; it gives more information about the detected object's depth, and improves object isolation and presentation. PMID- 26368086 TI - Model-based analysis on the influence of spatial frequency selection in spatial frequency domain imaging. AB - Frequency variation in spatial frequency domain imaging is a powerful tool for adjusting the penetration depth of the imaging signal and the parameter sensitivity toward absorption and diffusive and subdiffusive scattering. Through our computational analysis, using an analytical solution of the radiative transfer equation, we add quantitation to this tool by linking the different spatial frequency regimes to their relative information content and to their absolute depth sensitivity. Special focus is placed on high spatial frequencies by analysis of the phase function parameter gamma and its significance and ambiguity in describing subdiffusive scattering. PMID- 26368087 TI - Dielectric property of MoS(2) crystal in terahertz and visible regions. AB - Two-dimensional materials such as MoS2 have attracted much attention in recent years due to their fascinating optoelectronic properties. The dielectric response of MoS2 crystal in both the terahertz (THz) and visible regions is studied in this work. Time-domain THz spectroscopy is employed for the THz property investigation. The real and imaginary parts of the complex dielectric constant of MoS2 crystal are found to follow a Drude model, which is due to the intrinsic carrier absorption. In the visible region, ellipsometry is used to investigate the dielectric response. The general trend of the complex dielectric constant is found to be described with a Lorentz model, while two remarkable dielectric response peaks are observed to be located at 1.85 and 2.03 eV, which has been attributed to the splitting arising from the combined effect of interlayer coupling and spin-orbit coupling. This work can be the research foundation for future optoelectronic applications with MoS2. PMID- 26368088 TI - Spectrum reconstruction using relative-deviation-based kernel regression in temporally and spatially modulated Fourier transform imaging spectrometer. AB - During the temporally and spatially modulated Fourier transform imaging spectrometer push-broom scanning process, the motion state of the spectrometer platform can vary. Thus, the target interferogram obtained from the image sequence deviates from the ideal interferogram obtained using high platform stability. The recovered target spectrum will not reflect the true target characteristics. We adopted target tracking to acquire the target position in the image sequence via a proposed kernel regression, with a relative deviation method for determining the target intensities, and the recovery of the spectrogram using the nonuniform fast Fourier transform algorithm. We tested our algorithm on simulated and experimentally obtained aerial images and, from comparison with accurate spectrograms, demonstrate the effectiveness of the proposed method. PMID- 26368089 TI - Extended x-ray absorption fine structure measurements on asymmetric bipolar pulse direct current magnetron sputtered Ta(2)O(5) thin films. AB - Tantalum pentoxide (Ta2O5) thin films have been deposited on fused silica substrates using a novel asymmetric bipolar DC magnetron sputtering technique under a mixed ambient of oxygen and argon. Films have been prepared at different oxygen-to-argon ratios, and the sputtering ambient and optical properties of the films have been investigated by spectroscopic ellipsometry, while the structural analysis of the films has been carried out by grazing incidence x-ray diffraction and extended x-ray absorption fine structure (EXAFS) measurements. The concentration of oxygen and tantalum in the Ta2O5 films has been estimated by Rutherford backscattering spectrometry (RBS). The variation of the optical constants of the films with changes in deposition parameters has been explained in the light of the change in average Ta-O bond lengths and oxygen coordination around Ta sites as obtained from EXAFS measurements. The trend in variation of the oxygen-to-tantalum ratio in the films obtained from RBS measurement, as a function of oxygen partial pressure used during sputtering, is found to follow the trend in variation of the oxygen coordination number around Ta sites obtained from EXAFS measurement. PMID- 26368090 TI - Study on the staggered array of an LED system for improved thermal behavior. AB - This paper proposes a staggered array to minimize heat concentration of an LED system. The purpose of this paper is to investigate temperature distribution with and without an optimized process of an LED system in various placements by experimental and numerical methods in order to improve thermal behavior. The proposed work develops an effective method to design an LED's placement for enhanced thermal uniformity and luminous efficacy, thus decreasing thermal concentrations and temperature of the LED system. Measured and calculated temperature distribution of the LED system shows good agreement. PMID- 26368091 TI - Low-frequency noise effect on terahertz tomography using thermal detectors. AB - In this paper, the impact of low-frequency noise on terahertz-computed tomography (THz-CT) is analyzed for several measurement configurations and pyroelectric detectors. We acquire real noise data from a continuous millimeter-wave tomographic scanner in order to figure out its impact on reconstructed images. Second, noise characteristics are quantified according to two distinct acquisition methods by (i) extrapolating from experimental acquisitions a sinogram for different noise backgrounds and (ii) reconstructing the corresponding spatial distributions in a slice using a CT reconstruction algorithm. Then we describe the low-frequency noise fingerprint and its influence on reconstructed images. Thanks to the observations, we demonstrate that some experimental choices can dramatically affect the 3D rendering of reconstructions. Thus, we propose some experimental methodologies optimizing the resulting quality and accuracy of the 3D reconstructions, with respect to the low-frequency noise characteristics observed during acquisitions. PMID- 26368092 TI - Correction of pathlength amplification in the filter-pad technique for measurements of particulate absorption coefficient in the visible spectral region. AB - Spectrophotometric measurement of particulate matter retained on filters is the most common and practical method for routine determination of the spectral light absorption coefficient of aquatic particles, ap(lambda), at high spectral resolution over a broad spectral range. The use of differing geometrical measurement configurations and large variations in the reported correction for pathlength amplification induced by the particle/filter matrix have hindered adoption of an established measurement protocol. We describe results of dedicated laboratory experiments with a diversity of particulate sample types to examine variation in the pathlength amplification factor for three filter measurement geometries; the filter in the transmittance configuration (T), the filter in the transmittance-reflectance configuration (T-R), and the filter placed inside an integrating sphere (IS). Relationships between optical density measured on suspensions (ODs) and filters (ODf) within the visible portion of the spectrum were evaluated for the formulation of pathlength amplification correction, with power functions providing the best functional representation of the relationship for all three geometries. Whereas the largest uncertainties occur in the T method, the IS method provided the least sample-to sample variability and the smallest uncertainties in the relationship between ODs and ODf. For six different samples measured with 1 nm resolution within the light wavelength range from 400 to 700 nm, a median error of 7.1% is observed for predicted values of ODs using the IS method. The relationships established for the three filter-pad methods are applicable to historical and ongoing measurements; for future work, the use of the IS method is recommended whenever feasible. PMID- 26368093 TI - Three-visible-light wave combiner based on photonic crystal microcavities. AB - We propose a three-visible-light wave combiner based on two-dimensional square lattice photonic crystal (PhC) microcavities. A coupled-cavity waveguide is introduced to reduce the insertion losses for the three waves in the combiner. The transmission characteristic of light waves in PhCs with point defects is analyzed. As an example, a combiner for combining light waves of 488, 532, and 635 nm, which are commonly used as the three primary colors in laser display systems, is designed and demonstrated through the finite-difference time-domain method. The three visible light waves of 488, 532, and 635 nm are output at the same output port with transmittances of 97.6%, 98.1%, and 90.0%, respectively. The results show that the proposed device can perform efficient synthesis and the designing method can be applied in building other combiners based on PhCs made of dispersion materials. PMID- 26368094 TI - Microphysical characterization of free space optical link due to hydrometeor and fog effects. AB - Free space optics (FSO) channel availability is affected by atmospheric water particles, which may introduce severe path attenuation. A unified microphysically oriented atmospheric particle scattering (MAPS) model is proposed and described to simulate particle scattering effects on FSO links. Atmospheric particles, such as raindrops, graupel particles, and snowflakes, together with fog droplets, are considered. Input data to characterize liquid and frozen water particle size distribution, density, and refractivity are derived from available literature data and measurements. Scattering, absorption, and extinction coefficients as well as the asymmetry factor are numerically simulated for each particle class and then parametrized with respect to particle water content, fall rate, and visibility, spanning from visible to infrared wavelengths. Both single- and multiple-scattering effects are discussed and quantified by using a radiative transfer model for small-angle approximation. MAPS simulations confirm that fog layers are those causing the largest power extinction on FSO links, but also several decibels of attenuation can be attributed to snow and rain conditions. Multiple-scattering effects, especially due to fog droplets, heavy rain, and dry snowflakes, typically tend to reduce the total attenuation by increasing the received power. An estimate of these effects, parameterized to single-scattering extinction, is proposed for near-infrared FSO link design. PMID- 26368095 TI - Holographic humidity response of slanted gratings in moisture-absorbing acrylamide photopolymer. AB - Holographic humidity response is characterized in detail using transmission and reflection geometry in moisture-absorbing acrylamide photopolymer. The diffraction spectrum and its temporal evolution at various relative humidity are measured and analyzed. The quantitative relations between relative humidity and holographic properties of slanted gratings are determined. The responsibility of holographic gratings for various relative humidity is observed by the spectrum response of gratings. The extracted humidity constants reflect the applicability of reflection and transmission gratings at different humidity regions. The humidity reversibility experiment is achieved for confirming repeatability of the sensor. These experiments provide a probability for improving the applicability of a holographic humidity sensor. Finally, the extended diffusion model is derived by introducing the expansion coefficient to describe the dynamic swelling process. This work can accelerate development of the holographic sensor and provide a novel strategy for exploring the swelling mechanism of photopolymer. PMID- 26368096 TI - Determination of defect densities from spatiotemporally resolved optical-laser induced damage measurements. AB - A procedure is developed to retrieve defect densities of optical coatings and surfaces from spatiotemporally resolved optical-laser induced damage (STEREO-LID) measurements. In STEREO-LID, the temporal onset and location of nanosecond laser damage initiation is measured for each excitation event. The power of STEREO-LID relative to traditional damage tests resulting in damage probabilities is characterized with LID data from Monte Carlo simulations. PMID- 26368097 TI - Generation of trapezoidal illumination for the step-and-scan lithographic system. AB - To meet the uniform dose exposure in optical lithography, it is desirable to get uniform illumination and trapezoidal illumination in the scanning direction on the wafer for the step-and-scan lithographic system. A design strategy for trapezoidal illumination is proposed which offers both high uniformity illumination and fixed integral energy of trapezoidal illumination in a different illumination pattern. The strategy describes a light uniform device which contains a microlens array, a microcylindrical array, and a Fourier lens and produces trapezoidal illumination directly at the scanning slit. Compared with the conventional method to obtain the trapezoidal illumination, the strategy in this paper reduces the difficulty of assembly and has the advantage of simplicity and directness without blocking energy. This method utilizes energy of the lithographic system more effectively, and it improves the throughput of the lithography. The simulation results show that this method not only maintains the uniformity of trapezoidal illumination but also improves the energy utilization. PMID- 26368098 TI - Energy transfer and visible-infrared quantum cutting photoluminescence modification in Tm-Yb codoped YPO(4) inverse opal photonic crystals. AB - YPO4: Tm, Yb inverse opal photonic crystals were successfully synthesized by the colloidal crystal templates method, and the visible-infrared quantum cutting (QC) photoluminescence properties of YPO4: Tm, Yb inverse opal photonic crystals were investigated. We obtained tetragonal phase YPO4 in all the samples when the samples sintered at 950 degrees C for 5 h. The visible emission intensity of Tm3+ decreased significantly when the photonic bandgap was located at 650 nm under 480 nm excitation. On the contrary, the QC emission intensity of Yb3+ was enhanced as compared with the no photonic bandgap sample. When the photonic bandgap was located at 480 nm, the Yb3+ and Tm3+ light-emitting intensity weakened at the same time. We demonstrated that the energy transfer between Tm3+ and Yb3+ is enhanced by the suppression of the red emission of Tm3+. Additionally, the mechanisms for the influence of the photonic bandgap on the energy transfer process of the Tm3+, Yb3+ codoped YPO4 inverse opal are discussed. PMID- 26368099 TI - Observation of motion of colloidal particles undergoing flowing Brownian motion using self-mixing laser velocimetry with a thin-slice solid-state laser. AB - We achieved a highly sensitive method for observing the motion of colloidal particles in a flowing suspension using a self-mixing laser Doppler velocimeter (LDV) comprising a laser-diode-pumped thin-slice solid-state laser and a simple photodiode. We describe the measurement method and the optical system of the self mixing LDV for real-time measurements of the motion of colloidal particles. For a condensed solution, when the light scattered from the particles is reinjected into the solid-state laser, the laser output is modulated in intensity by the reinjected laser light. Thus, we can capture the motion of colloidal particles from the spectrum of the modulated laser output. For a diluted solution, when the relaxation oscillation frequency coincides with the Doppler shift frequency, fd, which is related to the average velocity of the particles, the spectrum reflecting the motion of the colloidal particles is enhanced by the resonant excitation of relaxation oscillations. Then, the spectral peak reflecting the motion of colloidal particles appears at 2*fd. The spectrum reflecting the motion of colloidal particles in a flowing diluted solution can be measured with high sensitivity, owing to the enhancement of the spectrum by the thin-slice solid-state laser. PMID- 26368100 TI - Thermoforming mechanism of precision glass moulding. AB - Precision glass moulding (PGM) enables the production of an aspherical lens and irregular optical products in a single step, but its product quality depends highly on the control of both material properties and process parameters. This paper investigates the thermoforming mechanism of a glass lens in PGM. To precisely describe the material behavior in PGM, a modulus-based constitutive model was framed and integrated with the finite element analysis. This model can be parameterized conveniently by an impulse excitation technique. Key processing parameters that influence the final profile and residual stresses of a lens were identified with the aid of dimensional analysis. The study found that the cooling stage above the glass transition temperature can bring about large geometry deviations of a lens. The residual stresses in a lens depend mainly on the temperature history in the supercooled liquid region caused by the variability and heterogeneity of thermal expansion. However, the stresses can be reduced effectively by decreasing the cooling rate from moulding temperature to glass transition temperature. PMID- 26368101 TI - Multi-physics simulation and fabrication of a compact 128 * 128 micro-electro mechanical system Fabry-Perot cavity tunable filter array for infrared hyperspectral imager. AB - This paper demonstrates the design and fabrication of a 128*128 micro-electro mechanical systems Fabry-Perot (F-P) cavity filter array, which can be applied for the hyperspectral imager. To obtain better mechanical performance of the filters, F-P cavity supporting structures are analyzed by multi-physics finite element modeling. The simulation results indicate that Z-arm is the key component of the structure. The F-P cavity array with Z-arm structures was also fabricated. The experimental results show excellent parallelism of the bridge deck, which agree with the simulation results. A conclusion is drawn that Z-arm supporting structures are important to hyperspectral imaging system, which can achieve a large tuning range and high fill factor compared to straight arm structures. The filter arrays have the potential to replace the traditional dispersive element. PMID- 26368102 TI - Applying slope constrained Qbfs aspheres for asphericity redistribution in the design of infrared transmission spheres. AB - An achromatic transmission sphere (TS) must be provided as an accessory for an infrared interferometer with a broadband wavelength channel. When designing an F/0.75 infrared TS using the one-asphere model of the two-lens-only package, the first surface was optimized as a strong asphere beyond our current testing ability, using either a slope-unconstrained Qbfs asphere equal to a conventional even asphere, or using a slope-constrained Qbfs asphere. We applied the asphere splitting theory to redistribute the asphericity. Adopting only the slope constrained Qbfs asphere, the strong asphere was successfully split into two weaker aspheres within our testing ability, getting a more manufacturable two asphere TS solution. Besides, the TS solution with two weaker aspheres presented the same sensitivity to assembly errors compared to the solution with one strong asphere, as demonstrated by the analysis of the wavefront aberrations of the TS solutions. This phenomenon coincides well with the asphere-splitting theory, given that the total asphericity remains almost equivalent between the two solutions. PMID- 26368103 TI - Graphics processing unit-assisted real-time three-dimensional measurement using speckle-embedded fringe. AB - This paper presents a novel two-frame fringe projection technique for real-time, accurate, and unambiguous three-dimensional (3D) measurement. One of the frames is a digital speckle pattern, and the other one is a composite image which is generated by fusing that speckle image with sinusoidal fringes. The contained sinusoidal component is used to obtain a wrapped phase map by Fourier transform profilometry, and the speckle image helps determine the fringe order for phase unwrapping. Compared with traditional methods, the proposed pattern scheme enables measurements of discontinuous surfaces with only two frames, greatly reducing the number of required patterns and thus reducing the sensitivity to movements. This merit makes the method very suitable for inspecting dynamic scenes. Moreover, it shows close performance in measurement accuracy compared with the phase-shifting method from our experiments. To process data in real time, a Compute Unified Device Architecture-enabled graphics processing unit is adopted to accelerate some time-consuming computations. With our system, measurements can be performed at 21 frames per second with a resolution of 307,000 points per frame. PMID- 26368104 TI - Improved method of attack on an asymmetric cryptosystem based on phase-truncated Fourier transform. AB - We propose an improved method of attack on an asymmetric cryptosystem based on a phase-truncated Fourier transform. With the proposed method of attack, an attacker is able to access the exact decryption keys and obtain precise attack results. The method is based on a novel median-filtering phase-retrieval algorithm. Compared with existing attacks, the proposed attack has the following advantages: (1) exact information of the original image can be obtained in gray scale and binary forms; (2) better computing efficiency; (3) more robust against noise and occlusion contaminations. Numerical simulation results show the effectiveness and robustness of the proposed method. Based on the proposed method of attack, we further propose a new cryptosystem, which not only enhances the security of the system but also does not require truncated phases. PMID- 26368105 TI - Optically switchable diffraction grating in a photochromic/polymer thin film. AB - An optically switchable diffraction grating has been made in a thin film containing a photochromic dye and amorphous polycarbonate. We show that a film containing the dye 5-chloro-1,3-dihydro-1,3,3-trimethylspiro[2H-indole 2,3'-(3H)naphth[2,1-b](1,4)oxazine] can be optically processed so that a diffraction grating can be completely switched on by ultraviolet light and turned off by thermal relaxation. The ability to switch or modulate the diffraction efficiency has a number of practical applications that include optical switches and add/drop multiplexers. PMID- 26368106 TI - Enhanced facial texture illumination normalization for face recognition. AB - An uncontrolled lighting condition is one of the most critical challenges for practical face recognition applications. An enhanced facial texture illumination normalization method is put forward to resolve this challenge. An adaptive relighting algorithm is developed to improve the brightness uniformity of face images. Facial texture is extracted by using an illumination estimation difference algorithm. An anisotropic histogram-stretching algorithm is proposed to minimize the intraclass distance of facial skin and maximize the dynamic range of facial texture distribution. Compared with the existing methods, the proposed method can more effectively eliminate the redundant information of facial skin and illumination. Extensive experiments show that the proposed method has superior performance in normalizing illumination variation and enhancing facial texture features for illumination-insensitive face recognition. PMID- 26368107 TI - Self-focusing of tightly focused laser beams. AB - Laser-induced damage (LID) thresholds of pure fused silica have been measured with single-temporal-mode nanosecond pulses at 1.064 MUm. The laser beam was focused by spherical lens or axicon into 2.7 MUm diameter spots with identical cross-sectional distribution of the central lobe irradiances. The measurements have shown about a 30% higher threshold value for the beam focused by the axicon, which is inherently not subjected to self-focusing. This result indicates the strong influence of self-focusing on standard LID threshold measurements performed even with tightly focused beams. PMID- 26368108 TI - Noise analysis of the Vernier anode. AB - In this work, the partition noise and the electronic noise of the Vernier anode are thoroughly analyzed based on the theory of statistical variation and error analysis. A new method calculating the inter-electrode capacitance of the Vernier anode is proposed, and the electronic noise's effect is discussed in detail, which is useful for the optimal design of a Vernier anode in the induced charge mode. The calculated results of the inter-electrode capacitance for a 0.891 mm period Vernier anode are in good agreement with the measured results. PMID- 26368109 TI - Additive manufacturing of a monolithic optical force sensor based on polarization modulation. AB - One of the specific interests of optical sensors is their compatibility with harsh environments. The polarization modulated force sensor we propose offers this advantage, in addition to low cost and ease of manufacturing thanks to its acrylate 3D printed monolithic design. All the polarization control is indeed achieved using the geometry of a single component making unnecessary future alignments. The complex geometry of the transducer is obtained thanks to the 3D printing process. This process and the resulting material optical properties are described. The sensor concept and the fabrication method are experimentally investigated. A monolithic force sensor in the required range of 20 N is exhibited for application in the field of MR-compatible robotics. The potentiality of 3D printing for optical application in the design of the force sensor is illustrated. PMID- 26368110 TI - Fast stimulated emission nanoscopy based on single molecule localization. AB - For super-resolution microscopy methods based on single molecule stochastic switching and localization, to simultaneously improve the spatial-temporal resolution, it is necessary to maximize the number of photons that can be collected from single molecules per unit time. Here, we describe a novel approach to enhance the signal intensity (collected photons per second) from fluorescence probes by introducing a stimulated emission (SE) optical process. This process is based on the following two properties: first, with reasonable parameters, the photon emission rate can be significantly increased with SE; and second, the SE photons, which are spatially coherent with the stimulation beam, are more favorable for collection than fluorescence. Theoretical results have shown that signal intensity from a single fluorescent molecule can be greatly improved with SE. We therefore showed, using SE in combination with single molecule localization methodology, that fast imaging at a rate of 0.05 s per reconstructed image with lateral resolutions of ~30 nm can be obtained. PMID- 26368111 TI - Micro-optical design of a three-dimensional microlens scanner for vertically integrated micro-opto-electro-mechanical systems. AB - This paper presents the optical design of a miniature 3D scanning system, which is fully compatible with the vertical integration technology of micro-opto electro-mechanical systems (MOEMS). The constraints related to this integration strategy are considered, resulting in a simple three-element micro-optical setup based on an afocal scanning microlens doublet and a focusing microlens, which is tolerant to axial position inaccuracy. The 3D scanning is achieved by axial and lateral displacement of microlenses of the scanning doublet, realized by micro electro-mechanical systems microactuators (the transmission scanning approach). Optical scanning performance of the system is determined analytically by use of the extended ray transfer matrix method, leading to two different optical configurations, relying either on a ball lens or plano-convex microlenses. The presented system is aimed to be a core component of miniature MOEMS-based optical devices, which require a 3D optical scanning function, e.g., miniature imaging systems (confocal or optical coherence microscopes) or optical tweezers. PMID- 26368112 TI - Evaluation of fluorescent dye degradation indirectly induced by x-ray ionizing radiation. AB - This work evaluated the fluorescent dye degradation indirectly induced by ionizing radiation with high energy photons (50 keV). Aqueous gels of agarose with low concentrations of Rhodamine 6G and Fluorescein were submitted to doses of x-ray radiation up to 200 Gy. The dye degradation was analyzed by fluorescence spectroscopy, using an excitation light-emitting diode with a peak wavelength of 462 nm. A rate equation model of fluorophores and radicals' species populations was developed to describe the degradation time behavior of the fluorescent solutions. The model suggests fluorescent dyes should be used in dosimetry. PMID- 26368113 TI - Precision influence of a phase retrieval algorithm in fractional Fourier domains from position measurement error. AB - An iterative structure of amplitude-phase retrieval (APR) was proved to obtain more accurate reconstructed data of both amplitude and phase. However, there is not enough analysis of the precise influence from position measurement error and corresponding error correction. We apply the APR in fractional Fourier domains to reconstruct a sample image and describe the corresponding optical implementation. The error model is built to discuss the distribution of the position measurement error. A corrective method is applied to amend the error and obtain a better quality of retrieved image. The numerical results have demonstrated that our methods are feasible and useful to correct the error for various circumstances. PMID- 26368114 TI - Multiple beam interference model for measuring parameters of a capillary. AB - A multiple beam interference model based on the ray tracing method and interference theory is built to analyze the interference patterns of a capillary tube filled with a liquid. The relations between the angular widths of the interference fringes and the parameters of both the capillary and liquid are derived. Based on these relations, an approach is proposed to simultaneously determine four parameters of the capillary, i.e., the inner and outer radii of the capillary, the refractive indices of the liquid, and the wall material. PMID- 26368115 TI - 3D optical two-mirror scanner with focus-tunable lens. AB - The paper presents formulas for a ray tracing in the optical system of two-mirror optical scanner with a focus-tunable lens. Furthermore, equations for the calculation of focal length which ensure focusing of a beam in the desired point in a detection plane are derived. The uncertainty description of such focal length follows as well. The chosen vector approach is general; therefore, the application of formulas in various configurations of the optical systems is possible. In the example situation, the authors derived formulas for mirrors' rotations and the focal length depending on the position of the point in the detection plane. PMID- 26368117 TI - The Journey to Establish CGRP as a Migraine Target: A Retrospective View. AB - In this retrospective, Dr. Lars Edvinsson recounts early steps and milestones in our understanding of the neuropeptide calcitonin gene-related peptide (CGRP) in the trigeminovascular system and its role in migraine. The discovery of the presence and function of CGRP and other neuropeptides in the cerebral vasculature and its sensory innervation is described. He relates the seminal finding that CGRP is uniquely released during migraine and the journey to develop blockers of CGRP effects. Now, over 30 years since its discovery, CGRP has become the target for a number of promising novel treatments for migraine patients. PMID- 26368118 TI - Basic Self-Disturbance in the Schizophrenia Spectrum: Taking Stock and Moving Forward. AB - The concept of basic self-disturbance offers a renewed, phenomenologically oriented framework to approach both the cross-sectional and longitudinal complexity of schizophrenia spectrum psychopathology. According to this approach, schizophrenia is characterized by instability in the most foundational and irreducible dimension of selfhood, i.e., the basic sense of self. Whereas normal basic self-experience is characterized by being a self-present, single, temporally persistent, bodily and demarcated (bounded) subject of experience and action, vulnerability to schizophrenia is marked by several structural shifts in such a basic selfhood (e.g., unstable first-person perspective, diminished sense of presence, and loss of vital contact with reality). This provides the ground for the emergence of the varied symptoms of schizophrenia, such as positive, negative and disorganization symptoms. Recent empirical research confirms that basic self-disturbance is specific to the schizophrenia spectrum and might be of value in the prospective identification of prodromal patients. The concept has implications for both aetiopathogenetic research and clinical-psychotherapeutic intervention. Furthermore, it may offer an integrative framework across 'levels' of inquiry in schizophrenia research (i.e. across psychopathological, neurocognitive and neurobiological domains). PMID- 26368119 TI - Organoantimony(III)-Containing Tungstoarsenates(III): From Controlled Assembly to Biological Activity. AB - A family of three sandwich-type, phenylantimony(III)-containing tungstoarsenates(III), [(PhSb(III) ){Na(H2 O)}As(III) 2 W19 O67 (H2 O)](11-) (1), [(PhSb(III) )2 As(III) 2 W19 O67 (H2 O)](10-) (2), and [(PhSb(III) )3 (B-alpha As(III) W9 O33 )2 ](12-) (3), have been synthesized by one-pot procedures and isolated as hydrated alkali metal salts, Cs3 K3.5 Na4.5 [(PhSb(III) ){Na(H2 O)}As(III) 2 W19 O67 (H2 O)]?41H2 O (CsKNa-1), Cs4.5 K5.5 [(PhSb(III) )2 As(III) 2 W19 O67 (H2 O)]?35H2 O (CsK-2), and Cs4.5 Na7.5 [(PhSb(III) )3 (B-alpha-As(III) W9 O33 )2 ]?42H2 O (CsNa-3). The number of incorporated {PhSb(III) } units could be selectively tuned from one to three by careful control of the reaction parameters. The three compounds were characterized in the solid state by single crystal XRD, IR spectroscopy, and thermogravimetric analysis. The aqueous solution stability of sandwich polyanions 1-3 was also studied by multinuclear ((1) H, (13) C, (183) W) NMR spectroscopy. Effective inhibitory activity against six different kinds of bacteria was identified for all three polyanions, for which the activity increased with the number of incorporated {PhSb(III) } groups. PMID- 26368120 TI - Is There a Role for Therapeutic Drug Monitoring of Anti-TNF Monoclonal Antibodies in Inflammatory Bowel Disease. AB - In recent years it has become clear that therapeutic drug monitoring can be an important tool to optimize outcome and costs of anti TNF treatment including the subcutaneous and fully human monoclonal antibodies. There is a clear dose response curve between early serum concentrations of all monoclonal antibodies and response both short term and long term. The wide variations in early serum concentrations are insufficiently explained by classic pharmacokinetic factors. Low early concentrations can lead to anti-drug antibody formation and ensuing loss of response. Therapeutic drug monitoring allows to rationalize the current practice of dose optimization and the use of concomitant immunomodulator treatment. However more prospective studies are needed before strong recommendations can enter treatment guidelines. PMID- 26368122 TI - Correction: Automated Peritoneal Dialysis Is Associated with Better Survival Rates Compared to Continuous Ambulatory Peritoneal Dialysis: A Propensity Score Matching Analysis. PMID- 26368121 TI - Human Cystathionine-beta-Synthase Phosphorylation on Serine227 Modulates Hydrogen Sulfide Production in Human Urothelium. AB - Urothelium, the epithelial lining the inner surface of human bladder, plays a key role in bladder physiology and pathology. It responds to chemical, mechanical and thermal stimuli by releasing several factors and mediators. Recently it has been shown that hydrogen sulfide contributes to human bladder homeostasis. Hydrogen sulfide is mainly produced in human bladder by the action of cystathionine-beta synthase. Here, we demonstrate that human cystathionine-beta-synthase activity is regulated in a cGMP/PKG-dependent manner through phosphorylation at serine 227. Incubation of human urothelium or T24 cell line with 8-Bromo-cyclic-guanosine monophosphate (8-Br-cGMP) but not dibutyryl-cyclic-adenosine monophosphate (d cAMP) causes an increase in hydrogen sulfide production. This result is congruous with the finding that PKG is robustly expressed but PKA only weakly present in human urothelium as well as in T24 cells. The cGMP/PKG-dependent phosphorylation elicited by 8-Br-cGMP is selectively reverted by KT5823, a specific PKG inhibitor. Moreover, the silencing of cystathionine-beta-synthase in T24 cells leads to a marked decrease in hydrogen sulfide production either in basal condition or following 8-Br-cGMP challenge. In order to identify the phosphorylation site, recombinant mutant proteins of cystathionine-beta-synthase in which Ser32, Ser227 or Ser525 was mutated in Ala were generated. The Ser227Ala mutant cystathionine-beta-synthase shows a notable reduction in basal biosynthesis of hydrogen sulfide becoming unresponsive to the 8-Br-cGMP challenge. A specific antibody that recognizes the phosphorylated form of cystathionine-beta-synthase has been produced and validated by using T24 cells and human urothelium. In conclusion, human cystathionine-beta-synthase can be phosphorylated in a PKG-dependent manner at Ser227 leading to an increased catalytic activity. PMID- 26368124 TI - Visual Saliency Prediction and Evaluation across Different Perceptual Tasks. AB - Saliency maps produced by different algorithms are often evaluated by comparing output to fixated image locations appearing in human eye tracking data. There are challenges in evaluation based on fixation data due to bias in the data. Properties of eye movement patterns that are independent of image content may limit the validity of evaluation results, including spatial bias in fixation data. To address this problem, we present modeling and evaluation results for data derived from different perceptual tasks related to the concept of saliency. We also present a novel approach to benchmarking to deal with some of the challenges posed by spatial bias. The results presented establish the value of alternatives to fixation data to drive improvement and development of models. We also demonstrate an approach to approximate the output of alternative perceptual tasks based on computational saliency and/or eye gaze data. As a whole, this work presents novel benchmarking results and methods, establishes a new performance baseline for perceptual tasks that provide an alternative window into visual saliency, and demonstrates the capacity for saliency to serve in approximating human behaviour for one visual task given data from another. PMID- 26368123 TI - Evapotranspiration Cycles in a High Latitude Agroecosystem: Potential Warming Role. AB - As the acreages of agricultural lands increase, changes in surface energetics and evapotranspiration (ET) rates may arise consequently affecting regional climate regimes. The objective of this study was to evaluate summertime ET dynamics and surface energy processes in a subarctic agricultural farm in Interior Alaska. The study includes micrometeorological and hydrological data. Results covering the period from June to September 2012 and 2013 indicated consistent energy fractions: LE/Rnet (67%), G/Rnet (6%), H/Rnet (27%) where LE is latent heat flux, Rnet is the surface net radiation, G is ground heat flux and H is the sensible heat flux. Additionally actual surface evapotranspiration from potential evaporation was found to be in the range of 59 to 66%. After comparing these rates with those of most prominent high latitude ecosystems it is argued here that if agroecosystem in high latitudes become an emerging feature in the land use, the regional surface energy balance will significantly shift in comparison to existing Arctic natural ecosystems. PMID- 26368125 TI - High Mercury Wet Deposition at a "Clean Air" Site in Puerto Rico. AB - Atmospheric mercury deposition measurements are rare in tropical latitudes. Here we report on seven years (April 2005 to April 2012, with gaps) of wet Hg deposition measurements at a tropical wet forest in the Luquillo Mountains, northeastern Puerto Rico, U.S. Despite receiving unpolluted air off the Atlantic Ocean from northeasterly trade winds, during two complete years the site averaged 27.9 MUg m(-2) yr(-1) wet Hg deposition, or about 30% more than Florida and the Gulf Coast, the highest deposition areas within the U.S. These high Hg deposition rates are driven in part by high rainfall, which averaged 2855 mm yr(-1). The volume-weighted mean Hg concentration was 9.8 ng L(-1), and was highest during summer and lowest during the winter dry season. Rainout of Hg (decreasing concentration with increasing rainfall depth) was minimal. The high Hg deposition was not supported by gaseous oxidized mercury (GOM) at ground level, which remained near global background concentrations (<10 pg m(-3)). Rather, a strong positive correlation between Hg concentrations and the maximum height of rain detected within clouds (echo tops) suggests that droplets in high convective cloud tops scavenge GOM from above the mixing layer. The high wet Hg deposition at this "clean air" site suggests that other tropical areas may be hotspots for Hg deposition as well. PMID- 26368126 TI - Effects of Presentation Rate and Attention on Auditory Discrimination: A Comparison of Long-Latency Auditory Evoked Potentials in School-Aged Children and Adults. AB - Decoding human speech requires both perception and integration of brief, successive auditory stimuli that enter the central nervous system as well as the allocation of attention to language-relevant signals. This study assesses the role of attention on processing rapid transient stimuli in adults and children. Cortical responses (EEG/ERPs), specifically mismatch negativity (MMN) responses, to paired tones (standard 100-100 Hz; deviant 100-300 Hz) separated by a 300, 70 or 10 ms silent gap (ISI) were recorded under Ignore and Attend conditions in 21 adults and 23 children (6-11 years old). In adults, an attention-related enhancement was found for all rate conditions and laterality effects (L>R) were observed. In children, 2 auditory discrimination-related peaks were identified from the difference wave (deviant-standard): an early peak (eMMN) at about 100 300 ms indexing sensory processing, and a later peak (LDN), at about 400-600 ms, thought to reflect reorientation to the deviant stimuli or "second-look" processing. Results revealed differing patterns of activation and attention modulation for the eMMN in children as compared to the MMN in adults: The eMMN had a more frontal topography as compared to adults and attention played a significantly greater role in childrens' rate processing. The pattern of findings for the LDN was consistent with hypothesized mechanisms related to further processing of complex stimuli. The differences between eMMN and LDN observed here support the premise that separate cognitive processes and mechanisms underlie these ERP peaks. These findings are the first to show that the eMMN and LDN differ under different temporal and attentional conditions, and that a more complete understanding of children's responses to rapid successive auditory stimulation requires an examination of both peaks. PMID- 26368128 TI - alpha-Mangostin Regulates Hepatic Steatosis and Obesity through SirT1-AMPK and PPARgamma Pathways in High-Fat Diet-Induced Obese Mice. AB - Previous studies have shown that alpha-mangostin (alpha-MG) suppresses intracellular fat accumulation and stimulation of lipolysis in in vitro systems. Together with the relatively high distribution of alpha-MG in liver and fat, these observations made it possible to propose a plausible hypothesis that an alpha-MG supplement may regulate hepatic steatosis and obesity. An alpha-MG supplement (50 mg/kg) reduced the body weight gain (13.8%) and epidymal and retroperitoneal fat mass accumulation (15.0 and 11.3%, respectively), as well as the biochemical serum profiles such as cholesterol [TC (26.9%), LDL-C (39.1%), and HDL-C (15.3%)], glucose (30.2%), triglyceride (29.7%), and fatty acid (30.3%) levels in high-fat fed mice compared with the high-fat diet-treated group, indicating that alpha-MG may regulate lipid metabolism. In addition, an alpha-MG supplement up-regulated hepatic AMPK, SirT1, and PPARgamma levels compared with the high-fat diet states, suggesting that alpha-MG regulates hepatic steatosis and obesity through the SirT1-AMPK and PPARgamma pathways in high-fat diet induced obese mice. PMID- 26368127 TI - Pro-Oxidant Activity of Amine-Pyridine-Based Iron Complexes Efficiently Kills Cancer and Cancer Stem-Like Cells. AB - Differential redox homeostasis in normal and malignant cells suggests that pro oxidant-induced upregulation of cellular reactive oxygen species (ROS) should selectively target cancer cells without compromising the viability of untransformed cells. Consequently, a pro-oxidant deviation well-tolerated by nonmalignant cells might rapidly reach a cell-death threshold in malignant cells already at a high setpoint of constitutive oxidative stress. To test this hypothesis, we took advantage of a selected number of amine-pyridine-based Fe(II) complexes that operate as efficient and robust oxidation catalysts of organic substrates upon reaction with peroxides. Five of these Fe(II)-complexes and the corresponding aminopyridine ligands were selected to evaluate their anticancer properties. We found that the iron complexes failed to display any relevant activity, while the corresponding ligands exhibited significant antiproliferative activity. Among the ligands, none of which were hemolytic, compounds 1, 2 and 5 were cytotoxic in the low micromolar range against a panel of molecularly diverse human cancer cell lines. Importantly, the cytotoxic activity profile of some compounds remained unaltered in epithelial-to-mesenchymal (EMT)-induced stable populations of cancer stem-like cells, which acquired resistance to the well known ROS inducer doxorubicin. Compounds 1, 2 and 5 inhibited the clonogenicity of cancer cells and induced apoptotic cell death accompanied by caspase 3/7 activation. Flow cytometry analyses indicated that ligands were strong inducers of oxidative stress, leading to a 7-fold increase in intracellular ROS levels. ROS induction was associated with their ability to bind intracellular iron and generate active coordination complexes inside of cells. In contrast, extracellular complexation of iron inhibited the activity of the ligands. Iron complexes showed a high proficiency to cleave DNA through oxidative-dependent mechanisms, suggesting a likely mechanism of cytotoxicity. In summary, we report that, upon chelation of intracellular iron, the pro-oxidant activity of amine pyrimidine-based iron complexes efficiently kills cancer and cancer stem-like cells, thus providing functional evidence for an efficient family of redox directed anti-cancer metallodrugs. PMID- 26368129 TI - Multicolor Melting Curve Analysis-Based Multilocus Melt Typing of Vibrio parahaemolyticus. AB - Vibrio parahaemolyticus is the leading cause of seafood-borne gastroenteritis outbreaks. To track the source of these diseases in a timely manner, a high throughput typing method is critical. We hereby describe a novel genotyping method for V. parahaemolyticus, termed multilocus melt typing (MLMT), based on multilocus sequence typing (MLST). MLMT utilizes melting curve analysis to interrogate the allelic types of a set of informative single nucleotide polymorphisms (SNPs) derived from the housekeeping genes used in MLST. For each SNP, one allelic type generates distinct Tm values, which are converted into a binary code. Multiple SNPs thus generate a series of binary codes, forming a melt type (MT) corresponding with a sequence type (ST) of MLST. Using a set of 12 SNPs, the MLMT scheme could resolve 218 V.parahaemolyticus isolates into 50 MTs corresponding with 56 STs. The discriminatory power of MLMT and MLST was similar with Simpson's index of diversity of 0.638 and 0.646, respectively. The global (adjusted Rand index = 0.982) and directional congruence (adjusted Wallace coefficient, MT->ST = 0.965; ST->MT = 1.000) between the two typing approaches was high. The entire procedure of MLMT could be finished within 3 h with negligible hands on time in a real-time PCR machine. We conclude that MLMT provides a reliable and efficient approach for V. parahaemolyticus genotyping and might also find use in other pathogens. PMID- 26368130 TI - Rapid Prediction of Treatment Futility of Boceprevir with Peginterferon-Ribavirin for Taiwanese Treatment Experienced Hepatitis C Virus Genotype 1-Infected Patients. AB - The efficacy and safety of the boceprevir (BOC)-containing triple therapy in Taiwanese treatment-experienced patients remains elusive. After 4 weeks of peginterferon/ribavirin lead-in therapy, patients with cirrhosis or previous null response received triple therapy for 44 weeks; whereas others received 32 weeks of triple therapy followed by 12 weeks of peginterferon/ribavirin therapy. Patients with HCV RNA > 100 IU/mL at week 12 or with detectable HCV RNA at week 24 of treatment were viewed as futile. A total of 123 patients received treatment. The rates of sustained virological response (SVR) and relapse were 66.7% and 8.9%, respectively by using intention-to-treat analysis. Multivariate analysis revealed that factors associated with SVR included HCV-1b (odds ratio [OR]/ 95% confidence intervals [CI]: 19.23/1.76-525.15, P = 0.01), BOC adherence (7.69/1.55-48.78, P = 0.01), serum albumin (OR/CI:6.25/1.14-40.07, P = 0.03) levels and HCV RNA levels (OR/CI:0.34/0.12-0.79, P = 0.01). Twenty-six (21.1%) patients experienced severe adverse events (SAEs). Multivariate analysis revealed that APRI > 1.5 was the single factor associated with occurring SAEs (OR/CI: 3.77/ 0.97-14.98, P = 0.05). Merging the cut-off values of HCV RNA > 7 log IU/mL at baseline and HCV RNA > 6 log IU/mL at week 4 provided the earliest and best combing viral kinetics in predicting week 12/24 futility with the PPV of 100% and accuracy of 93.5%. HCV-1 treatment experienced Taiwanese patients treated with boceprevir-containing triple therapy in real world had comparable efficacy and safety profiles with those reported in clinical trials. Early viral kinetics before week 4 of treatment highly predicted futility at week 12 or 24 of treatment. PMID- 26368131 TI - Gait Kinematic Analysis in Water Using Wearable Inertial Magnetic Sensors. AB - Walking is one of the fundamental motor tasks executed during aquatic therapy. Previous kinematics analyses conducted using waterproofed video cameras were limited to the sagittal plane and to only one or two consecutive steps. Furthermore, the set-up and post-processing are time-consuming and thus do not allow a prompt assessment of the correct execution of the movements during the aquatic session therapy. The aim of the present study was to estimate the 3D joint kinematics of the lower limbs and thorax-pelvis joints in sagittal and frontal planes during underwater walking using wearable inertial and magnetic sensors. Eleven healthy adults were measured during walking both in shallow water and in dry-land conditions. Eight wearable inertial and magnetic sensors were inserted in waterproofed boxes and fixed to the body segments by means of elastic modular bands. A validated protocol (Outwalk) was used. Gait cycles were automatically segmented and selected if relevant intraclass correlation coefficients values were higher than 0.75. A total of 704 gait cycles for the lower limb joints were normalized in time and averaged to obtain the mean cycle of each joint, among participants. The mean speed in water was 40% lower than that of the dry-land condition. Longer stride duration and shorter stride distance were found in the underwater walking. In the sagittal plane, the knee was more flexed (~ 23 degrees ) and the ankle more dorsiflexed (~ 9 degrees ) at heel strike, and the hip was more flexed at toe-off (~ 13 degrees ) in water than on land. On the frontal plane in the underwater walking, smoother joint angle patterns were observed for thorax-pelvis and hip, and ankle was more inversed at toe-off (~ 7 degrees ) and showed a more inversed mean value (~ 7 degrees ). The results were mainly explained by the effect of the speed in the water as supported by the linear mixed models analysis performed. Thus, it seemed that the combination of speed and environment triggered modifications in the joint angles in underwater gait more than these two factors considered separately. The inertial and magnetic sensors, by means of fast set-up and data analysis, can supply an immediate gait analysis report to the therapist during the aquatic therapy session. PMID- 26368133 TI - Surface Adsorption of Oppositely Charged SDS:C(12)TAB Mixtures and the Relation to Foam Film Formation and Stability. AB - The complexation, surface adsorption, and foam film stabiliztation of the oppositely charged surfactants, sodium dodecyl sulfate (SDS) and dodecyl trimethylammonium bromide (C12TAB), is analyzed. The SDS:C12TAB mixing ratio is systematically varied to investigate whether the adsorption of equimolar or irregular catanionic surfactant complexes, and thus a variation in surface charge (i.e., surface excess of either SDS or C12TAB), governs foam film properties. Surface tension measurements indicate that SDS and C12TAB interact electrostatically in order to form stoichometric catanionic surfactant complexes and enhance surface adsorption. On the other hand it can be demonstrated that the SDS:C12TAB mixing ratio and, thus, a change in surface charge and composition plays a decisive role in foam film stabilization. The present study demonstrates that varying the mixing ratio between SDS and C12TAB offers a tool for tailoring surface composition and foam film properties, which are therefore not exclusively mediated by the presence of equimolar catanionic surfactant complexes. The SDS:C12TAB net amount and mixing ratio determine the type, stability, and thinning behavior of the corresponding foam film. These observations indicate the formation of a mixed surface layer, composed of the catanionic surfactant species surrounded by either free SDS or C12TAB molecules in excess. Furthermore, a systematic variation in CBF-NBF transition kinetics is rationalized on the basis of a microscopic phase transition within the foam films. Fundamental knowlegde gained from this research gives insight into the surface adsorption and foam film formation of catanionic surfactant mixtures. The study helps researchers to understand basic mechanisms of foam film stabilization and to use resources more efficiently. PMID- 26368134 TI - A Simple Algorithm for Finding All k-Edge-Connected Components. AB - The problem of finding k-edge-connected components is a fundamental problem in computer science. Given a graph G = (V, E), the problem is to partition the vertex set V into {V1, V2,..., Vh}, where each Vi is maximized, such that for any two vertices x and y in Vi, there are k edge-disjoint paths connecting them. In this paper, we present an algorithm to solve this problem for all k. The algorithm preprocesses the input graph to construct an Auxiliary Graph to store information concerning edge-connectivity among every vertex pair in O(Fn) time, where F is the time complexity to find the maximum flow between two vertices in graph G and n = ?V?. For any value of k, the k-edge-connected components can then be determined by traversing the auxiliary graph in O(n) time. The input graph can be a directed or undirected, simple graph or multigraph. Previous works on this problem mainly focus on fixed value of k. PMID- 26368132 TI - Heat-Induced Radiolabeling of Nanoparticles for Monocyte Tracking by PET. AB - Heat-induced radiolabeling (HIR) yielded (89) Zr-Feraheme (FH) nanoparticles (NPs) that were used to determine NP pharmacokinetics (PK) by positron emission tomography (PET). Standard uptake values indicated a fast hepatic uptake that corresponded to blood clearance, and a second, slow uptake process by lymph nodes and spleen. By cytometry, NPs were internalized by circulating monocytes and monocytes in vitro. Using an IV injection of HIR (89) Zr-FH (rather than in vitro cell labeling), PET/PK provided a view of monocyte trafficking, a key component of the immune response. PMID- 26368135 TI - Improved spatiotemporal-multiplexing super-multiview display based on planar aligned OLED microdisplays. AB - Through gating spectrum plane of multiple planar aligned OLED microdisplays by a timely sequential manner, a super-multiview (SMV) three-dimensional (3D) display based on spatiotemporal-multiplexing was developed in our previous paper. But an upper limit of the allowable sub-viewing-zones (SVZs) for an OLED microdisplay did exist in the previous system, even if microdisplays with very high frame rates could be commercially available. In this manuscript, an improved spatiotemporal-multiplexing SMV displays system is developed, which removes the above limitation through controllable fusing of light beams from adjacent OLED microdisplays. The employment of a liquid-crystal panel as the gating-aperture array allows the improved system to accommodate multiple rows of OLED microdisplays for denser SVZs. Experimentally, a prototype system is demonstrated by 24 OLED microdisplays, resulting in 120 SVZs with an interval small to 1.07mm. PMID- 26368136 TI - Ergodic capacity analysis for DF strategies in cooperative FSO systems. AB - This paper focuses on the ergodic capacity analysis in the context of cooperative free-space optical (FSO) systems when the line of sight is available. Novel asymptotic closed-form expressions for the ergodic capacity corresponding to two different decode-and-forward (DF) strategies are obtained for a cooperative FSO communication system. Here, the atmospheric turbulence is modeled by a gamma gamma distribution of parameters alpha and beta which allows to study a wide range of turbulence conditions (moderate-to-strong) as well as the effect of the misalignment with zero boresight. It is demonstrated that cooperative communications are able to achieve not only a better performance in terms of the error rate performance as well as outage probability than direct transmission, but also in terms of the channel capacity in the context of FSO systems without much increase in hardware. In this way, a 3-way FSO communication setup is considered, in which the cooperative protocol can be applied to achieve a greater ergodic capacity compared to a direct transmission. It can be concluded that a greater and robust capacity strongly dependent on the relay location is achieved compared to a direct transmission without cooperative communication when line of sight is available. Here, the line of sight is taken into account in order to achieve a significant robustness under different turbulence conditions and more severe pointing errors regardless of the relay location. Simulation results are further demonstrated to confirm the accuracy and usefulness of the derived results. PMID- 26368137 TI - Topological edge modes in multilayer graphene systems. AB - Plasmons can be supported on graphene sheets as the Dirac electrons oscillate collectively. A tight-binding model for graphene plasmons is a good description as the field confinement in the normal direction is strong. With this model, the topological properties of plasmonic bands in multilayer graphene systems are investigated. The Zak phases of periodic graphene sheet arrays are obtained for different configurations. Analogous to Su-Schrieffer-Heeger (SSH) model in electronic systems, topological edge plasmon modes emerge when two periodic graphene sheet arrays with different Zak phases are connected. Interestingly, the dispersion of these topological edge modes is the same as that in the monolayer graphene and is invariant as the geometric parameters of the structure such as the separation and period change. These plasmonic edge states in multilayer graphene systems can be further tuned by electrical gating or chemical doping. PMID- 26368138 TI - Determination of the effective index and thickness of biomolecular layer by Fano resonances in gold nanogrid array. AB - We present an accurate method to determine the effective refractive index and thickness of biomolecular layer by using Fano resonance modes in dual-period gold nanogrid arrays. The effective refractive index changes along the x and y directions are simultaneously measured and obtained by using a modified dispersion relation. The thickness of the surface layer is calculated by a three layer waveguide equation without any fitting parameters. The accuracy of the proposed method is verified by comparing the results with the known coated dielectric layer and self-assembly layers. The applications of this method and nanogrid chips for determining the thickness and surface concentration of antigen/antibody interactions are demonstrated. PMID- 26368139 TI - Spatio-TEmporally REsolved Optical Laser Induced Damage (STEREO LID) technique for material characterization. AB - A technique for measuring the ablation and laser-induced damage threshold (LIDT) by identifying the temporal onset of damage and location of initiation within the beam profile is demonstrated. This new method, dubbed Spatio-TEmporally REsolved Optical Laser Induced Damage (STEREO LID), is compared to traditional damage tests and its advantages are exemplified. PMID- 26368140 TI - Analysis of frequency response of high power MUTC photodiodes based on photocurrent-dependent equivalent circuit model. AB - A back-illuminated mesa-structure InGaAs/InP modified uni-traveling-carrier photodiode (MUTC-PD) is fabricated and its frequency response is investigated. A bandwidth of 40 GHz and a saturation photocurrent up to 33 mA are demonstrated. A photocurrent-dependent equivalent circuit model is proposed to analyze the frequency response of the high power MUTC-PDs. The influences of the space-charge screening, self-induced electric field and over-shoot effects are discussed in detail based on the model. Fitted curves obtained from the simple equivalent circuit model are found to be in good agreement with the data measured under different bias voltages and photocurrents. PMID- 26368141 TI - Broadband thin-film polarizer for 12 fs applications. AB - A broadband non-dispersive thin-film polarizer for ultrafast applications is presented. The polarizer has a controllable flat-phase and a high extinction ratio of 23:1 in the working bandwidth from 680 nm to 900 nm. This bandwidth allows supporting laser pulses down to 12 fs. The unavoidable mechanical stress of the interference coating is completely compensated by a specially designed antireflection coating on the second side of the substrate, allowing the use of thin substrates. PMID- 26368142 TI - Hitless tunable WDM transmitter using Si photonic crystal optical modulators. AB - We have developed compact Si Mach-Zehnder modulators that are assisted by wideband low-dispersion slow light in lattice-shifted photonic crystal waveguides. We have also developed Si triangular-shaped coupled-microring multiplexers that allow a box-like spectrum, a wide free spectral range, and an efficient thermal tuning. In this study, we integrated three sets of these devices in a small footprint of 2.0 * 0.7 mm(2) and achieved their 25 Gbps/ch operation as a wavelength division multiplexing transmitter. Moreover, we demonstrated hitless wavelength tuning using thermo-optic switches loaded in the bus waveguide. PMID- 26368143 TI - Exact wavefronts and caustic surfaces produced by planar ripple lenses. AB - We obtain simple exact formulas for both caustic and refracted wavefronts through smooth surfaces by considering an incident plane wavefront propagating along the optical axis, providing a condition for total internal reflection (TIR). On the other hand, a formula to provide the maximum slopes for refracted rays outside of the lens is directly related to the condition to obtain the inflection points on the refracting surface. Demanding simultaneously both conditions can potentially provide the shape for an optimized surface which reduces the gap produced by TIR and to refract efficiently all the light outside of the lens. This has a wide potential in applications on the field of non-imagining systems and illumination. PMID- 26368144 TI - Dynamical studies of the mechanisms for optical nonlinearities of methyl-red dye doped blue phase liquid crystals. AB - Dynamical grating diffraction experiments and reflection/transmission polarization spectroscopy have been conducted on azo-dye doped Blue-Phase Liquid Crystal (BPLC) to investigate the mechanisms responsible for laser induced refractive index changes. The underlying mechanisms for the transient grating diffraction components are attributed to thermal indexing and lattice distortion, whereas the persistent component is due to lattice distortion/expansion caused by laser excited dye molecule isomerization. These mechanisms were distinguishable by their response dynamics and gave rise to the observed reflection spectra and photonic bandgap shift, polarization dependency and optical activity. Some preliminary studies have demonstrated the feasibility of using these mechanisms for coherent holographic and direct image writing operations. PMID- 26368145 TI - Electrical and ultraviolet characterization of 4H-SiC Schottky photodiodes. AB - Fabrication and electrical and optical characterization of 4H-SiC Schottky UV photodetectors with nickel silicide interdigitated contacts is reported. Dark capacitance and current measurements as a function of applied voltage over the temperature range 20 degrees C - 120 degrees C are presented. The results show consistent performance among devices. Their leakage current density, at the highest investigated temperature (120 degrees C), is in the range of nA/cm(2) at high internal electric field. Properties such as barrier height and ideality factor are also computed as a function of temperature. The responsivities of the diodes as functions of applied voltage were measured using a UV spectrophotometer in the wavelength range 200 nm - 380 nm and compared with theoretically calculated values. The devices had a mean peak responsivity of 0.093 A/W at 270 nm and -15 V reverse bias. PMID- 26368146 TI - Exploration of photon-number entangled states using weak nonlinearities. AB - A method for exploring photon-number entangled states with weak nonlinearities is described. We show that it is possible to create and detect such entanglement at various scales, ranging from microscopic to macroscopic systems. In the present architecture, we suggest that the maximal phase shift induced in the process of interaction between photons is proportional to photon numbers. Also, in the absence of decoherence we analyze maximum error probability and show its feasibility with current technology. PMID- 26368147 TI - Practical and cost-effective high-fidelity optical carrier dissemination using coherent communication techniques. AB - We report a unidirectional frequency dissemination scheme for high-fidelity optical carriers deployable over telecommunication networks. For the first time, a 10 Gb/s Binary Phase Shift Keying (BPSK) signal from an ultra-narrow linewidth laser was transmitted through a field-installed optical fibre with round-trip length of 124 km between Cork City and town of Clonakilty, without inline optical amplification. At the receiver, using coherent communication techniques and optical injection-locking the carrier was recovered with noise suppression. The beat signal between the original carrier at the transmitter and recovered carrier at the receiver shows a linewidth of 2.8 kHz. Long term stability measurements revealed fractional instabilities (True Allan deviation) of 3.3 * 10(-14) for 1 s averaging time, prior to phase noise cancellation. PMID- 26368148 TI - Comparative study on three highly sensitive absorption measurement techniques characterizing lithium niobate over its entire transparent spectral range. AB - We employ three highly sensitive spectrometers: a photoacoustic spectrometer, a photothermal common-path interferometer and a whispering-gallery-resonator-based absorption spectrometer, for a comparative study of measuring the absorption coefficient of nominally transparent undoped, congruently grown lithium niobate for ordinarily and extraordinarily polarized light in the wavelength range from 390 to 3800 nm. The absorption coefficient ranges from below 10(-4) cm(-1) up to 2 cm(-1). Furthermore, we measure the absorption at the Urbach tail as well as the multiphonon edge of the material by a standard grating spectrometer and a Fourier-transform infrared spectrometer, providing for the first time an absorption spectrum of the whole transparency window of lithium niobate. The absorption coefficients obtained by the three highly sensitive and independent methods show good agreement. PMID- 26368149 TI - Systems performance comparison of three all-optical generation schemes for quasi Nyquist WDM. AB - Orthogonal time division multiplexing (OrthTDM) interleaves sinc-shaped pulses to form a high baud-rate signal, with a rectangular spectrum suitable for multiplexing into a Nyquist WDM (N-WDM)-like signal. The problem with generating sinc-shaped pulses is that they theoretically have infinite durations, and even if time bounded for practical implementation, they still require a filter with a long impulse response, hence a large physical size. Previously a method of creating chirped-orthogonal frequency division multiplexing (OFDM) pulses with a chirped arrayed waveguide (AWG) filter, then converting them into interleaved quasi-sinc pulses using dispersive fiber (DF), has been proposed. This produces a signal with a wider spectrum than the equivalent N-WDM signal. We show that a modification to the scheme enables the spectral extent to be reduced for the same data rate. We then analyse the key factors in designing an OrthTDM transmitter, and relate these to the performance of a N-WDM system. We show that the modified transmitter reduces the required guard band between the N-WDM channels. We also simulate a simpler scheme using an unchirped finite-impulse response filter of similar size, which directly creates truncated-sinc pulses without needing a DF. This gives better system performance than either chirped scheme. PMID- 26368150 TI - Effective increase in beam emittance by phase-space expansion using asymmetric Bragg diffraction. AB - We propose an innovative method to extend the utilization of the phase space downstream of a synchrotron light source for X-ray transmission microscopy. Based on the dynamical theory of X-ray diffraction, asymmetrically cut perfect crystals are applied to reshape the position-angle-wavelength space of the light source, by which the usable phase space of the source can be magnified by over one hundred times, thereby "phase-space-matching" the source with the objective lens of the microscope. The method's validity is confirmed using SHADOW code simulations, and aberration through an optical lens such as a Fresnel zone plate is examined via matrix optics for nano-resolution X-ray images. PMID- 26368151 TI - Two-photon excited fluorescence from a pseudoisocyanine-attached gold tip via a plasmonic-photonic hybrid system. AB - A plasmonic-photonic hybrid system with efficient coupling of light from a fiber coupled microspherical cavity to localized surface plasmon (LSP) modes of a gold coated tip was proposed, which was composed of a fiber-coupled microspherical cavity and a pseudoisocyanine (PIC)-attached gold tip. To prove efficient excitation of LSP at the gold-coated tip, we experimentally demonstrated two photon excited fluorescence from the PIC-attached gold-coated tip via a fiber coupled microspherical cavity under a weak continuous wave excitation condition. This hybrid system could focus the incident light with coupling efficiency of around 64% into a nanoscale domain of the metal tip with an effective area of a 79-nm circle. PMID- 26368152 TI - Efficient and versatile surface integral approach to light scattering in stratified media. AB - Recent advances in nano-optics elicit a growing need for more efficient numerical treatments of light-matter interaction in stratified backgrounds. While being known for its many favorable properties, usage of the surface integral approach is hindered by numerical difficulties associated with layered-medium Green's functions. We present an efficient and robust implementation of this approach, addressing the limiting issues. The singularity extraction method is generalized to account for the occurring secondary-term singularities. The resulting scheme thus allows for arbitrary positioning of the scatterers. Further, the laborious matrix-filling process is dramatically accelerated through a simple and robustly devised, spatial interpolation scheme, completely devoid of integral evaluations. The accuracy and versatility of the method are demonstrated by treating several representative plasmonic problems. PMID- 26368153 TI - Frequency-dependent linewidth enhancement factor of optical injection-locked quantum dot/dash lasers. AB - Combining theoretical and experimental studies show that optical injection strongly changes the behavior of the linewidth enhancement factor (alpha(H) factor) and the FM-to-AM indices ratio (FAIR) in quantum dash/dot semiconductor lasers. In contrast to solitary lasers, both the alpha(H)-factor and the FAIR at low-frequency modulation are reduced by optical injection. At high modulation frequency, however, the phase-amplitude coupling characteristics are little influenced by optical injection. PMID- 26368154 TI - Novel dual-function lens with microscopic and vari-focus capability incorporated with an aberration-suppression aspheric lens. AB - Substantial aberrations are ubiquitous in many conventional adaptive lenses due to the existence of deformable interface and thus inevitably compromise the optical performance. In this paper, we introduce a novel concept of dual-function fluidic lenses (DFFL) with a built-in aspheric polydimethylsiloxane lens (APL) to enable the design of a compact optical system with tunable imaging and aberration suppression properties. This is achieved by varying both hydrostatic pressures (i.e. adjusting the injected liquid volume change) such that a widely tunable focal length and the simultaneously integrated APL for aberrations correction. DFFL can transform to 4 modes: microscopic mode (APL only), APL/concave mode, APL/plano mode, and APL/convex mode. Focal tunability of DFFL from 12/8 mm to about 90/65 mm (DI water/ethanol) is demonstrated without any mechanical moving components. Aberration characterization is carried out systematically and the low cost, high performance microscopic mode can be easily achieved by actuating the contact between APL and PDMS membrane. In addition, DFFL turning to microscopic mode (focal length 7.32 mm and magnification 50X) can rival the images quality of commercial microscopes. PMID- 26368155 TI - Dual wavelength 3.2-MUm source for isotope ratio measurements of (13)CH(4)/(12)CH(4). AB - Difference frequency generation using one 1.58-MUm and two 1.06-MUm distributed feedback Bragg-grating laser diodes and a ridge-type PPLN alternately provide two 3.2-MUm coaxial waves resonant with individual isotopic transitions separated by 13 cm(-1). The nu(3) band R(6) A(2) allowed transition of (13)CH(4) and the nu(3) band R(6) A(2) weakly allowed transition of (12)CH(4) are an ideal pair for isotope ratio measurements. The (13)CH(4)/(12)CH(4) isotope ratio is determined for three sample gases with a relative uncertainty of 0.7 0/00, and it is confirmed that the temperature dependence is smaller than the uncertainty. PMID- 26368156 TI - Extended reach OFDM-PON using super-Nyquist image induced aliasing. AB - We investigate a novel dispersion compensating technique in double sideband (DSB) modulated and directed-detected (DD) passive optical network (PON) systems using super-Nyquist image induced aliasing. We show that diversity is introduced to the higher frequency components by deliberate aliasing using the super-Nyquist images. We then propose to use fractional sampling and per-subcarrier maximum ratio combining (MRC) to harvest this diversity. We evaluate the performance of conventional orthogonal frequency division multiplexing (OFDM) signals along with discrete Fourier transform spread (DFT-S) OFDM and code-division multiplexing OFDM (CDM-OFDM) signals using the proposed scheme. The results show that the DFT S OFDM signal has the best performance due to spectrum spreading and its superior peak-to-average power ratio (PAPR). By using the proposed scheme, the reach of a 10-GHz bandwidth QPSK modulated OFDM-PON can be extended to around 90 km. We also experimentally show that the achievable data rate of the OFDM signals can be effectively increased using the proposed scheme when adaptive bit loading is applied, depending on the transmission distance. A 10.5% and 5.2% increase in the achievable bit rate can be obtained for DSB modulated OFDM-PONs in 48.3-km and 83.2-km standard single mode fiber (SSMF) transmission cases, respectively, without any modification on the transmitter. A 40-Gb/s OFDM transmission over 83.2-km SSMF is successfully demonstrated. PMID- 26368157 TI - Design of optical metamaterial mirror with metallic nanoparticles for floating gate graphene optoelectronic devices. AB - The purpose of this work is to conceive the idea for using the gate dielectrics of floating-gate memory device (i.e., Au nanoparticle (AuNP) monolayer embedded within polymeric matrix) as a magnetic mirror, so as to harness the broadband light absorption of thin film optoelectronics. In particular, we systematically examined whether the versatile assembly of spherical AuNP monolayer can be indeed treated as the effective magnetic mirror for floating-gate graphene optoelectronic device. High amenability of the AuNP assembly with the large-area device fabrication procedures may make this strategy widely applicable to various thin film optoelectronic devices. Our study thereby advances the design of mirror for thin film optoelectronics. PMID- 26368158 TI - High-brightness spectral beam combining of diode laser array stack in an external cavity. AB - We demonstrate the spectral beam combining of a diode laser stack, which contains three 970nm Mini-Bars along the fast-axis direction, in an external cavity. At the pump current of 60 A, the output power of 127 W, the spectral bandwidth of 12 nm and the Electro-optical conversion efficiency of 48.35% are achieved. The measured beam qualities after the spectral beam combining are M(2) ~10.2 along the slow axis and M(2) ~11.5 along the fast axis. Under a maximum injection current of 75A, the laser output power of more than 159W is achieved. The beam quality deteriorated slightly with the rising of the current from 60A to 75A, but it is enough to be coupled into a 50um core / 0.22NA fiber. PMID- 26368159 TI - UV LED array based NLOS UV turbulence channel modeling and experimental verification. AB - In this paper, we comprehensively study the NLOV UV turbulence effect through simulated and experimental results. A Monte Carlo NLOS UV turbulence channel model, which incorporates the effects of multiple scattering and turbulence attenuation, is proposed based on previous work. To validate this model, a series of outdoor experiments is conducted to investigate the received-signal energy distribution and channel path loss under the turbulence circumstance for the first time. These experimental and simulated results are valuable for studying NLOS UV channel and communication system design. PMID- 26368160 TI - Frequency comb offset dynamics of SESAM modelocked thin disk lasers. AB - We present a detailed study of the carrier-envelope offset (CEO) frequency dynamics of SESAM modelocked thin disk lasers (TDLs) pumped by kW-class highly transverse multimode pump diodes with a typical M(2) value of 200-300, and give guidelines for future frequency stabilization of multi-100-W oscillators. We demonstrate CEO frequency detection with > 30 dB signal-to-noise ratio with a resolution bandwidth of 100 kHz from a SESAM modelocked Yb:YAG TDL delivering 140 W average output power with 748-fs pulses at 7-MHz pulse repetition rate. We compare with a low-power CEO frequency stabilized Yb:CALGO TDL delivering 2.1 W with 77-fs pulses at 65 MHz. For both lasers, we perform a complete noise characterization, measure the relevant transfer functions (TFs) and compare them to theoretical models. The measured TFs are used to determine the propagation of the pump noise step-by-step through the system components. From the noise propagation analysis, we identify the relative intensity noise (RIN) of the pump diode as the main contribution to the CEO frequency noise. The resulting noise levels are not excessive and do not prevent CEO frequency stabilization. More importantly, the laser cavity dynamics are shown to play an essential role in the CEO frequency dynamics. The cavity TFs of the two lasers are very different which explains why at this point a tight CEO frequency lock can be obtained with the Yb:CALGO TDL but not with the Yb:YAG TDL. For CEO stabilization laser cavities should exhibit high damping of the relaxation oscillations by nonlinear intra cavity elements, for example by operating a SESAM in the roll-over regime. Therefore the optimum SESAM operation point is a trade-off between enough damping and avoiding multiple pulsing instabilities. Additional cavity components could be considered for supplementary damping independent of the SESAM operation point. PMID- 26368161 TI - Tunable delay control of entangled photons based on dispersion cancellation. AB - We propose and demonstrate a novel approach for controlling the temporal position of the biphoton correlation function using pump frequency tuning and dispersion cancellation; precise waveguide engineering enables biphoton generation at different pump frequencies while the idea of nonlocal dispersion cancellation is used to create the relative signal-idler delay and simultaneously prevents broadening of their correlation. Experimental results for delay shifts up to +/ 15 times the correlation width are shown along with discussions of the performance metrics of this approach. PMID- 26368162 TI - Phase-coded microwave signal generation based on a single electro-optical modulator and its application in accurate distance measurement. AB - A novel scheme for photonic generation of a phase-coded microwave signal is proposed and its application in one-dimension distance measurement is demonstrated. The proposed signal generator has a simple and compact structure based on a single dual-polarization modulator. Besides, the generated phase-coded signal is stable and free from the DC and low-frequency backgrounds. An experiment is carried out. A 2 Gb/s phase-coded signal at 20 GHz is successfully generated, and the recovered phase information agrees well with the input 13-bit Barker code. To further investigate the performance of the proposed signal generator, its application in one-dimension distance measurement is demonstrated. The measurement accuracy is less than 1.7 centimeters within a measurement range of ~2 meters. The experimental results can verify the feasibility of the proposed phase-coded microwave signal generator and also provide strong evidence to support its practical applications. PMID- 26368163 TI - Silicon-photonic PTAT temperature sensor for micro-ring resonator thermal stabilization. AB - We present a scheme for thermal stabilization of micro-ring resonator modulators through direct measurement of ring temperature using a monolithic PTAT temperature sensor. The measured temperature is used in a feedback loop to adjust the thermal tuner of the ring. The closed-loop feedback system is demonstrated to operate in presence of thermal perturbations at 20Gb/s. PMID- 26368164 TI - High power broadband LiF:F(2)(-) color center laser. AB - A high power LiF:F(2)(-) color center laser is demonstrated with broadband emission. The excitation source is a quasi-continuous wave diode side-pumped acousto-optically Q-switched Nd:YAG laser. Under an incident 1064-nm laser power of 25.4 W, the highest output power of up to 4.7 W is obtained with a macro pulse repetition rate of 400 Hz and a micro pulse repetition rate of 50 kHz. The broadband emission is centered at 1142 nm with a bandwidth of 13 nm. PMID- 26368165 TI - Design of 3D isotropic metamaterial device using smart transformation optics. AB - We report here a design method for a 3 dimensional (3D) isotropic transformation optical device using smart transformation optics. Inspired by solid mechanics, smart transformation optics regards a transformation optical medium as an elastic solid and deformations as coordinate transformations. Further developing from our previous work on 2D smart transformation optics, we introduce a method of 3D smart transformation optics to design 3D transformation optical devices by maintaining isotropic materials properties for all types of polarizations imposing free or nearly free boundary conditions. Due to the material isotropy, it is possible to fabricate such devices with structural metamaterials made purely of common dielectric materials. In conclusion, the practical importance of the method reported here lies in the fact that it enables us to fabricate, without difficulty, arbitrarily shaped 3D devices with existing 3D printing technology. PMID- 26368166 TI - Diffraction limited focusing and routing of gap plasmons by a metal-dielectric metal lens. AB - Passive optical elements can play key roles in photonic applications such as plasmonic integrated circuits. Here we experimentally demonstrate passive gap plasmon focusing and routing in two-dimensions. This is accomplished using a high numerical-aperture metal-dielectric-metal lens incorporated into a planar waveguide device. Fabrication via metal sputtering, oxide deposition, electron- and focused-ion- beam lithography, and argon ion-milling is reported on in detail. Diffraction-limited focusing is optically characterized by sampling out coupled light with a microscope. The measured focal distance and full-width-half maximum spot size agree well with the calculated lens performance. The surface plasmon polariton propagation length is measured by sampling light from multiple out-coupler slits. PMID- 26368167 TI - Upconversion luminescence from aluminoborate glasses doped with Tb(3+), Eu(3+) and Dy(3+) under the excitation of 2.6-MUm femtosecond laser pulses. AB - We investigated the upconversion luminescence of three aluminoborate glasses doped with Tb(3+), Eu(3+), and Dy(3+) under the excitation of 2.6-MUm femtosecond (fs) laser pulses. Efficient upconversion luminescence appearing in the visible light spectral region was observed in all three glasses and the emission spectra are quite similar to those obtained under single photon excitation. From the dependence of the luminescence intensity on the excitation intensity in the low excitation intensity regime, it was revealed that a four-photon process is involved in the generation of the upconversion luminescence in the Tb(3+)- and Eu(3+)-doped glasses while a mixed two- and three-photon process is involved in the Dy(3+)-doped glass. In the high excitation intensity regime, a reduction of the slope to about 1.0 was observed for all glasses. A physical mechanism based on the super saturation of the intermediate states of the rare-earth ions was employed to interpret the upconversion luminescence under the excitation of long wavelength fs laser pulses. Significantly broadened luminescence spectra were observed in thick glasses under high excitation intensities and it can be attributed to the self-focusing of the laser beam in the thick glasses. PMID- 26368168 TI - Multi-section core-shell InGaN/GaN quantum-well nanorod light-emitting diode array. AB - The growth of a two-section, core-shell, InGaN/GaN quantum-well (QW) nanorod- (NR ) array light-emitting diode device based on a pulsed growth technique with metalorganic chemical vapor deposition is demonstrated. A two-section n-GaN NR is grown through a tapering process for forming two uniform NR sections of different cross-sectional sizes. The cathodoluminescence (CL), photoluminescence (PL), and electrolumines-cence (EL) characterization results of the two-section NR structure are compared with those of a single-section NR sample, which is prepared under the similar condition to that for the first uniform NR section of the two-section sample. All the CL, PL, and EL spectra of the two-section sample (peaked between 520 and 525 nm) are red-shifted from those of the single-section sample (peaked around 490 nm) by >30 nm in wavelength. Also, the emitted spectral widths of the two-section sample become significantly larger than their counterparts of the single-section sample. The PL spectral full-width at half maximum increases from ~37 to ~61 nm. Such variations are attributed to the higher indium incorporation in the sidewall QWs of the two-section sample due to the stronger strain relaxation in an NR section of a smaller cross-sectional size and the more constituent atom supply from the larger gap volume between neighboring NRs. PMID- 26368170 TI - Stacked modulation formats enabling highest-sensitivity optical free-space links. AB - A new modulation scheme with a sensitivity of 2.3 photons per bit at a bit-error ratio (BER) of 10(-3) is discussed theoretically and demonstrated experimentally. We achieve a limiting sensitivity of 2.3 photons per bit (3.7 dB photons per bit) by stacking the modulation formats 64PPM, 4FSK and polarization-switched (PS) QPSK. This modulation stack encodes 11 bit per symbol (PPM: 6 bit, FSK: 2 bit, PS PQSK: 3 bit). We also replaced 4FSK by 2ODFM (2-channel multiplex) for comparison. With 64PPM-2OFDM-PS-QPSK a total of 12 bit are encoded (PPM: 6 bit, 2 OFDM channels with PS-QPSK: 2 * 3 bit). Both modulation stacks show a similar limiting sensitivity and are probably the highest sensitivities so far reported for a BER of 10(-3), Our theoretical considerations are supported by simulations and experiments. PMID- 26368169 TI - Wavefront correction and high-resolution in vivo OCT imaging with an objective integrated multi-actuator adaptive lens. AB - Adaptive optics is rapidly transforming microscopy and high-resolution ophthalmic imaging. The adaptive elements commonly used to control optical wavefronts are liquid crystal spatial light modulators and deformable mirrors. We introduce a novel Multi-actuator Adaptive Lens that can correct aberrations to high order, and which has the potential to increase the spread of adaptive optics to many new applications by simplifying its integration with existing systems. Our method combines an adaptive lens with an imaged-based optimization control that allows the correction of images to the diffraction limit, and provides a reduction of hardware complexity with respect to existing state-of-the-art adaptive optics systems. The Multi-actuator Adaptive Lens design that we present can correct wavefront aberrations up to the 4th order of the Zernike polynomial characterization. The performance of the Multi-actuator Adaptive Lens is demonstrated in a wide field microscope, using a Shack-Hartmann wavefront sensor for closed loop control. The Multi-actuator Adaptive Lens and image-based wavefront-sensorless control were also integrated into the objective of a Fourier Domain Optical Coherence Tomography system for in vivo imaging of mouse retinal structures. The experimental results demonstrate that the insertion of the Multi actuator Objective Lens can generate arbitrary wavefronts to correct aberrations down to the diffraction limit, and can be easily integrated into optical systems to improve the quality of aberrated images. PMID- 26368171 TI - Depth-based defocus map estimation using off-axis apertures. AB - This paper presents a depth-based defocus map estimation method from a single camera with multiple off-axis apertures. The proposed estimation algorithm consists of two steps: (i) object distance estimation using off-axis apertures and (ii) defocus map estimation based on the object distance. The proposed method can accurately estimate the defocus map using object distances that are well characterized in a color shift model-based computational camera. Experimental results show that the proposed method outperforms the state-of-the-art defocus estimation methods in the sense of both accuracy and the estimation range. The proposed defocus map estimation method is suitable for multifocusing, refocusing, and extended depth of field (EDoF) systems. PMID- 26368172 TI - Compact and low-cost THz QTDS system. AB - We present a terahertz quasi time domain spectroscopy (QTDS) system setup which is improved regarding cost and compactness. The diode laser is mounted directly onto the optical delay line, making the optical setup more compact. The system is operated using a Raspberry Pi and an additional sound card. This combination replaces the desktop/laptop computer, the lock-in-amplifier, the stage controller and the signal generator. We examined not only a commercially available stepper motor driven delay line, but also the repurposed internal mechanics from a DVD drive. We characterize the performance of the new system concept. PMID- 26368173 TI - Spaser operation below threshold: autonomous vs. driven spasers. AB - At the plasmon resonance, high Joule losses in a metal nanoparticle of a spaser result in its low Q-factor. Due to the latter, to achieve the spasing regime, in which the number of coherent plasmons exceeds the number of incoherent plasmons, unsustainably high pump rates may be required. We show that under the condition of loss compensation by a spaser driven by an external optical wave, the number of coherent plasmons increases dramatically, and the quantum noise is suppressed. Since the compensation of losses of the driving wave may occur even near the spasing threshold, the number of coherent plasmons may exceed the number of spontaneously excited plasmons at achievable pump rates. PMID- 26368174 TI - Spatial optical crosstalk in CMOS image sensors integrated with plasmonic color filters. AB - Imaging resolution of complementary metal oxide semiconductor (CMOS) image sensor (CIS) keeps increasing to approximately 7k * 4k. As a result, the pixel size shrinks down to sub-2MUm, which greatly increases the spatial optical crosstalk. Recently, plasmonic color filter was proposed as an alternative to conventional colorant pigmented ones. However, there is little work on its size effect and the spatial optical crosstalk in a model of CIS. By numerical simulation, we investigate the size effect of nanocross array plasmonic color filters and analyze the spatial optical crosstalk of each pixel in a Bayer array of a CIS with a pixel size of 1MUm. It is found that the small pixel size deteriorates the filtering performance of nanocross color filters and induces substantial spatial color crosstalk. By integrating the plasmonic filters in the low Metal layer in standard CMOS process, the crosstalk reduces significantly, which is compatible to pigmented filters in a state-of-the-art backside illumination CIS. PMID- 26368175 TI - Evaluation of complex gonioapparent samples using a bidirectional spectrometer. AB - Many applications use gonioapparent targets whose appearance depends on irradiation and viewing angles; the strongest effects are provided by light diffraction. These targets, optically variable devices (OVDs), are used in both security and authentication applications. This study introduces a bidirectional spectrometer, which enables to analyze samples with most complex angular and spectral properties. In our work, the spectrometer is evaluated with samples having very different types of reflection, concerning spectral and angular distributions. Furthermore, an OVD containing several different grating patches is evaluated. The device uses automatically adjusting exposure time to provide maximum signal dynamics and is capable of doing steps as small as 0.01 degrees . However, even 2 degrees steps for the detector movement showed that this device is more than capable of characterizing even the most complex reflecting surfaces. This study presents sRGB visualizations, discussion of bidirectional reflection, and accurate grating period calculations for all of the grating samples used. PMID- 26368176 TI - Sclerectomy with nanojoule energy level per pulse by femtosecond fiber laser in vitro. AB - The use of nanojoule femtosecond pulses (NFP) for highly precise proceeding in anti-glaucoma surgery was evaluated. According to the observation of scanning electron microscopy (SEM), four types of incision patterns, including subsurface, slit-like, spot and cuboid ablations, were accomplished on in vitro sclera by NFP with little collateral damage. In comparison to microjoule femtosecond pulses (MFP), NFP can make extremely precise incisions with smoother inner surface with less peak power density. The present study first illustrates the potential use of NFP in minimally invasive laser sclerectomy for glaucoma therapy. PMID- 26368177 TI - Negative refraction in molybdenum disulfide. AB - Recently, negative refractions have been demonstrated in uniaxial crystals with no necessary of negative permittivity and permeability. However, the small anisotropy parametergammain the uniaxial crystals limits the negative refraction occurrence only in a small range of the incident light angle, retarding its practical applications. In this paper, we report negative refraction induced by a pronounced anisotropic behavior in the bulk MoS(2). Using the first-principles, the dielectric function and refractive index calculations confirm a uniaxial trait of MoS(2) with a calculated anisotropy parametergammalarger than 2.5 in the entire range of visible wavelength. The critical incident angle to trigger a negative refraction in the bulk MoS(2) is calculated up to 90 degrees . The finite-difference time-domain simulations prove that the incident light with a density of 59.5% can be negatively refracted in a MoS(2) slab with a thickness of 0.1 um. Our results open up a new pathway for MoS(2)-like materials to a novel field of optical integration. PMID- 26368178 TI - 1.6 Gbit/s phosphorescent white LED based VLC transmission using a cascaded pre equalization circuit and a differential outputs PIN receiver. AB - We proposed a cascaded amplitude equalizer used for high speed visible light communications (VLC) system. With the cascaded pre-equalization circuit, the -3dB bandwidth of VLC system can be extended from 17MHz to 366MHz using a commercially available phosphorescent white LED, a blue filter and a differential outputs PIN receiver. The data rate is 1.60Gbit/s exploiting 16QAM-OFDM with 400MHz modulation bandwidth over 1m free-space transmission under pre-forward error correction (pre-FEC) limit of 3.8 * 10(-3). To our knowledge, this is the highest data rate ever achieved by using a commercially available phosphorescent white LED in VLC system. PMID- 26368179 TI - Sub-300-femtosecond operation from a MIXSEL. AB - Peak power scaling of semiconductor disk lasers is important for many applications, but their complex pulse formation mechanism requires a rigorous pulse characterization to confirm stable fundamental modelocking. Here we fully confirm sub-300-fs operation of Modelocked Integrated eXternal-cavity Surface Emitting Lasers (MIXSELs) with record high peak power at gigahertz pulse repetition rates. A strain-compensated InGaAs quantum well gain section enables an emission wavelength in the range of Yb-doped amplifiers at ~1030 nm. We demonstrate the shortest pulses from a MIXSEL with a duration of 253 fs with 240 W of peak power, the highest peak power generated from any MIXSEL to date. This peak power performance is comparable to conventional SESAM-modelocked VECSELs for the first time. At a 10-GHz pulse repetition rate we still obtained 279-fs pulses with 310 mW of average output power, which is currently the highest output power of any femtosecond MIXSEL. Continuous tuning of the pulse repetition rate has been demonstrated with sub-400-fs pulse durations and >225 mW of average output power between 2.9 and 3.4 GHz. The strain-compensated MIXSEL chip allowed for more detailed parameter studies with regards to different heat sink temperatures, pump power, and epitaxial homogeneity of the MIXSEL chip for the first time. We discuss in detail, how the critical temperature balance between quantum well gain and quantum well absorber, the partially saturated absorber and a limited epitaxial growth quality influence the overall device efficiency. PMID- 26368180 TI - Iterative optimization calibration method for stereo deflectometry. AB - An accurate system calibration method is presented in this paper to calibrate stereo deflectometry. A corresponding iterative optimization algorithm is also proposed to improve the system calibration accuracy. This merges CCD parameters and geometrical relation between CCDs and the LCD into one cost function. In this calibration technique, an optical flat acts as a reference mirror and simultaneously reflect sinusoidal fringe patterns into the two CCDs. The normal vector of the reference mirror is used as an intermediate variable to implement this iterative optimization algorithm until the root mean square of the reprojection errors converge to a minimum. The experiment demonstrates that this method can optimize all the calibration parameters and can effectively reduce reprojection error, which correspondingly improves the final reconstruction accuracy. PMID- 26368181 TI - Chromatic analysis and design of a first-order radial GRIN lens. AB - From the expression for optical power of a radial first-order graded-index (GRIN) lens with curved surfaces, we derive an expression for chromatic aberration. Our expressions for optical power and chromatic aberration are valid under the paraxial approximation. By applying a series of further simplifying assumptions, namely a thin lens and thin GRIN, we derive a set of equations with which one can design an achromatic GRIN lens. We also derive expressions for the dispersive property of a GRIN element. Our analysis enables us to derive the relationship between material pairs that indicate their suitability as a material pair for a GRIN achromat. We use this relationship to search a standard glass catalog for attractive GRIN material pairs for a particular achromat design. We compare the optical performance of our GRIN design to that of a conventional homogeneous doublet and demonstrate that our approach is capable of identifying material pairs that perform well for achromatic GRIN lenses which would not generally be considered for conventional achromatic design. We also demonstrate our approach is capable of designing GRIN achromats with superior performance. PMID- 26368182 TI - Integrated frequency comb source based Hilbert transformer for wideband microwave photonic phase analysis. AB - We demonstrate a photonic RF Hilbert transformer for broadband microwave in-phase and quadrature-phase generation based on an integrated frequency optical comb, generated using a nonlinear microring resonator based on a CMOS compatible, high index contrast, doped-silica glass platform. The high quality and large frequency spacing of the comb enables filters with up to 20 taps, allowing us to demonstrate a quadrature filter with more than a 5-octave (3 dB) bandwidth and an almost uniform phase response. PMID- 26368183 TI - Power splitting and switching in a multi-core fiber based on the multimode interference effect. AB - In this paper, we propose a novel 1 to N optical power splitter and a 1 to N optical switch for a multi-core fiber (MCF) with N circularly aligned cores. The splitter and the switch are based on the multimode interference (MMI) effect inside a ring core fiber. The MMI effect will convert one image into N output images in the ring and therefore, the ring shape MMI coupler can act as a 1 to N power splitter. These images will have different phases. If two ring shape MMI couplers are used and a tunable phase shifter array and a fixed phase shifter array are placed between them, by properly setting the phases of the N images in the middle of the MMI couplers, the images will converge to one output port of the 2nd MMI coupler. The output port number can be changed by tuning the phase shifters. In this way, the input signal at one of the cores of the MCF can be switched to the other core, and a 1 to N switch can be realized. In the analysis, it is found that only one control parameter is required for the phase adjustment of the tunable phase shifter array in order to achieve the switching between the cores. PMID- 26368184 TI - Highly stable atomic vector magnetometer based on free spin precession. AB - We present a magnetometer based on optically pumped Cs atoms that measures the magnitude and direction of a 1 MUT magnetic field. Multiple circularly polarized laser beams were used to probe the free spin precession of the Cs atoms. The design was optimized for long-time stability and achieves a scalar resolution better than 300 fT for integration times ranging from 80 ms to 1000 s. The best scalar resolution of less than 80 fT was reached with integration times of 1.6 to 6 s. We were able to measure the magnetic field direction with a resolution better than 10 MUrad for integration times from 10 s up to 2000 s. PMID- 26368185 TI - Polarization insensitive graphene saturable absorbers using etched fiber for highly stable ultrafast fiber lasers. AB - In this paper, we introduce a graphene-based saturable absorber (GSA) with high damage threshold employing symmetrical evanescent wave interaction for highly stable mode-locking of ultrafast fiber lasers. To enhance the evanescent wave interaction between the graphene layer and the propagating light, graphene flakes are mixed with polydimethylsiloxane (PDMS), and the graphene/PDMS composite is coated onto a chemically etched fiber. The GSA exhibits polarization insensitivity due to its symmetric cross-section, which enables stable operation against environmental disturbance such as stress, bending, and temperature variation. Finally, we demonstrate a fiber laser generating 216 fs pulses with an 80 dB signal-to-noise ratio. PMID- 26368186 TI - Condition for invariant spectrum of an electromagnetic wave scattered from an anisotropic random media. AB - Within the accuracy of the first-order Born approximation, sufficient conditions are derived for the invariance of spectrum of an electromagnetic wave, which is generated by the scattering of an electromagnetic plane wave from an anisotropic random media. We show that the following restrictions on properties of incident fields and the anisotropic media must be simultaneously satisfied: 1) the elements of the dielectric susceptibility matrix of the media must obey the scaling law; 2) the spectral components of the incident field are proportional to each other; 3) the second moments of the elements of the dielectric susceptibility matrix of the media are inversely proportional to the frequency. PMID- 26368187 TI - Broadband lightwave synthesized frequency sweeper using self-induced auto tracking filter. AB - We present a scheme to broaden the sweeping span of lightwave synthesized frequency sweeper (LSFS) by using self-induced auto-tracking filter (SIATF). It is based on spatial-hole-burning effect in unpumped erbium-doped fiber (EDF), equivalent to introducing a Bragg grating. This Bragg grating works as the SIAFT, tracks the frequency of the incident optical signal automatically. It broadens LSFS's sweeping span limited by the homogeneous broadening of EDF. The scheme is demonstrated experimentally that the amplified spontaneous emission (ASE) noise is effectively suppressed meanwhile sweeping span of LSFS is enlarged. 12.48nm sweeping span within 3.5dB power change is obtained, which corresponds to 1.56THz sweeping span. PMID- 26368188 TI - Single tapered fiber tip for simultaneous measurements of thickness, refractive index and distance to a sample. AB - We demonstrate the capability of an air cavity Fabry-Perot interferometer (FPI), built with a tapered lead-in fiber tip, to measure three parameters simultaneously, distance, group refractive index and thickness of transparent samples introduced in the cavity. Tapering the lead-in fiber enhances the light coupling back efficiency, therefore is possible to enlarge the air cavity without a significant deterioration of the fringe visibility. Fourier transformation, used to analyze the reflected optical spectrum of our FPI, simplify the calculus to determine the position, thickness and refractive index. Samples made of 7 different glasses; fused silica, BK7, BalF5, SF2, BaF51, SF15, and glass slides were used to test our FPI. Each sample was measured nine times and the results for position, thickness and refractive index showed differences of +/- 0.7%, +/- 0.1%, and +/- 0.16% respectively. The evolution of thickness and refractive index of a block of polydimethylsiloxane (PDMS) elastomer due to temperature changes in the range of 25 degrees C to 90 degrees C were also measured. The coefficients of the thermal expansion and thermo-optic estimated were alpha = 4.71x10(-4)/ degrees C and dn/dT = -4.66 x10(-4) RIU/ degrees C, respectively. PMID- 26368189 TI - Computer-generated holograms by multiple wavefront recording plane method with occlusion culling. AB - We propose a novel fast method for full parallax computer-generated holograms with occlusion processing, suitable for volumetric data such as point clouds. A novel light wave propagation strategy relying on the sequential use of the wavefront recording plane method is proposed, which employs look-up tables in order to reduce the computational complexity in the calculation of the fields. Also, a novel technique for occlusion culling with little additional computation cost is introduced. Additionally, the method adheres a Gaussian distribution to the individual points in order to improve visual quality. Performance tests show that for a full-parallax high-definition CGH a speedup factor of more than 2,500 compared to the ray-tracing method can be achieved without hardware acceleration. PMID- 26368190 TI - Optical multicast system for data center networks. AB - We present the design and experimental evaluation of an Optical Multicast System for Data Center Networks, a hardware-software system architecture that uniquely integrates passive optical splitters in a hybrid network architecture for faster and simpler delivery of multicast traffic flows. An application-driven control plane manages the integrated optical and electronic switched traffic routing in the data plane layer. The control plane includes a resource allocation algorithm to optimally assign optical splitters to the flows. The hardware architecture is built on a hybrid network with both Electronic Packet Switching (EPS) and Optical Circuit Switching (OCS) networks to aggregate Top-of-Rack switches. The OCS is also the connectivity substrate of splitters to the optical network. The optical multicast system implementation requires only commodity optical components. We built a prototype and developed a simulation environment to evaluate the performance of the system for bulk multicasting. Experimental and numerical results show simultaneous delivery of multicast flows to all receivers with steady throughput. Compared to IP multicast that is the electronic counterpart, optical multicast performs with less protocol complexity and reduced energy consumption. Compared to peer-to-peer multicast methods, it achieves at minimum an order of magnitude higher throughput for flows under 250 MB with significantly less connection overheads. Furthermore, for delivering 20 TB of data containing only 15% multicast flows, it reduces the total delivery energy consumption by 50% and improves latency by 55% compared to a data center with a sole non-blocking EPS network. PMID- 26368191 TI - Evaluation of 100G DP-QPSK long-haul transmission performance using second order co-pumped Raman laser based amplification. AB - We present, for the first time, a detailed investigation of the impact of second order co-propagating Raman pumping on long-haul 100G WDM DP-QPSK coherent transmission of up to 7082 km using Raman fibre laser based configurations. Signal power and noise distributions along the fibre for each pumping scheme were characterised both numerically and experimentally. Based on these pumping schemes, the Q factor penalties versus co-pump power ratios were experimentally measured and quantified. A significant Q factor penalty of up to 4.15 dB was observed after 1666 km using symmetric bidirectional pumping, compared with counter-pumping only. Our results show that whilst using co-pumping minimises the intra-cavity signal power variation and amplification noise, the Q factor penalty with co-pumping was too great for any advantage to be seen. The relative intensity noise (RIN) characteristics of the induced fibre laser and the output signal, and the intra-cavity RF spectra of the fibre laser are also presented. We attribute the Q factor degradation to RIN induced penalty due to RIN being transferred from the first order fibre laser and second order co-pump to the signal. More importantly, there were two different fibre lasing regimes contributing to the amplification. It was random distributed feedback lasing when using counter-pumping only and conventional Fabry-Perot cavity lasing when using all bidirectional pumping schemes. This also results in significantly different performances due to different laser cavity lengths for these two classes of laser. PMID- 26368192 TI - High performance frame synchronization for continuous variable quantum key distribution systems. AB - Considering a practical continuous variable quantum key distribution(CVQKD) system, synchronization is of significant importance as it is hardly possible to extract secret keys from unsynchronized strings. In this paper, we proposed a high performance frame synchronization method for CVQKD systems which is capable to operate under low signal-to-noise(SNR) ratios and is compatible with random phase shift induced by quantum channel. A practical implementation of this method with low complexity is presented and its performance is analysed. By adjusting the length of synchronization frame, this method can work well with large range of SNR values which paves the way for longer distance CVQKD. PMID- 26368193 TI - Efficient smoothed finite element time domain analysis for photonic devices. AB - In this paper, a new finite element method (FEM) is proposed to analyse time domain wave propagation in photonic devices. Dissimilar to conventional FEM, efficient "inter-element" matrices are accurately formed through smoothing the field derivatives across element boundaries. In this sense, the new approach is termed "smoothed FEM" (SFETD). For time domain analysis, the propagation is made via the time domain beam propagation method (TD-BPM). Relying on first order elements, our suggested SFETD-BPM enjoys accuracy levels comparable to second order conventional FEM; thanks to the element smoothing. The proposed method numerical performance is tested through applicating on analysis of a single mode slab waveguide, optical grating structure, and photonic crystal cavity. It is clearly demonstrated that our method is not only accurate but also more computationally efficient (far few run time, and memory requirements) than the conventional FEM approach. The SFETD-BPM is also extended to deal with the very challenging problem of dispersive materials. The material dispersion is smartly utilized to enhance the quality factor of photonic crystal cavity. PMID- 26368194 TI - Novel optical super-resolution pattern with upright edges diffracted by a tiny thin aperture. AB - In the past decade numerous efforts have been concentrated to achieve optical imaging resolution beyond the diffraction limit. In this letter a thin microcavity theory of near-field optics is proposed by using the power flow theorem firstly. According to this theory, the near-field optical diffraction from a tiny aperture whose diameter is less than one-tenth incident wavelength embedded in a thin conducting film is investigated by considering this tiny aperture as a thin nanocavity. It is very surprising that there exists a kind of novel super-resolution diffraction patterns showing resolution better than lambda/80 (lambda is the incident wavelength), which is revealed for the first time to our knowledge in this letter. The mechanism that has allowed the imaging with this kind of super-resolution patterns is due to the interaction between the incident wave and the thin nanocavity with a complex wavenumber. More precisely, these super-resolution patterns with discontinuous upright peaks are formed by one or three items of the integration series about the cylindrical waves according to our simulation results. This novel optical super-resolution with upright edges by using the thin microcavity theory presented in the study could have potential applications in the future semiconductor lithography process, nano size laser-drilling technology, microscopy, optical storage, optical switch, and optical information processing. PMID- 26368195 TI - Beam deflection measurement of bound-electronic and rotational nonlinear refraction in molecular gases. AB - A polarization-resolved beam deflection technique is used to separate the bound electronic and molecular rotational components of nonlinear refractive transients of molecular gases. Coherent rotational revivals from N(2), O(2), and two isotopologues of carbon disulfide (CS(2)), are identified in gaseous mixtures. Dephasing rates, rotational and centrifugal distortion constants of each species are measured. Polarization at the magic angle allows unambiguous measurement of the bound-electronic nonlinear refractive index of air and second hyperpolarizability of CS(2). Agreement between gas and liquid phase second hyperpolarizability measurements is found using the Lorentz-Lorenz local field correction. PMID- 26368196 TI - Faraday effect in hybrid magneto-plasmonic photonic crystals. AB - We present a theoretical study of the Faraday effect in hybrid magneto-plasmonic crystals that consist of Au-Co-Au perforated membranes with a periodic array of sub-wavelength holes. We show that in these hybrid systems the interplay between the extraordinary optical transmission and the magneto-optical activity leads to a resonant enhancement of the Faraday rotation, as compared to purely ferromagnetic membranes. In particular, we determine the geometrical parameters for which this enhancement is optimized and show that the inclusion of a noble metal like Au dramatically increases the Faraday rotation over a broad bandwidth. Moreover, we show that the analysis of the Faraday rotation in these periodically perforated membranes provides a further insight into the origin of the extraordinary optical transmission. PMID- 26368197 TI - Single germanium quantum dot embedded in photonic crystal nanocavity for light emitter on silicon chip. AB - A silicon light emitter in telecom-band based on a single germanium quantum dot precisely embedded in a silicon photonic crystal nanocavity is fabricated by a scalable method. A sharp resonant luminescence peak is observed at 1498.8 nm, which is enhanced by more than three orders of magnitude. The Purcell factor for the fundamental resonant mode is estimated from enhancement factor and increased collection efficiency. The cavity modes coupled to the ground state and excited state emission of germanium quantum dot are identified in the luminescence spectrum. Our devices provide a CMOS-compatible way of developing silicon-based low-power consuming light emitters, and are promising for realizing on-chip single photon sources. PMID- 26368198 TI - Index-profile design for low-loss crossed multimode waveguide for optical printed circuit board. AB - We present an index profile design for remarkably low loss multimode optical crossed waveguide. In this paper, we theoretically calculate the light propagation loss in crossed waveguides with step-index (SI) and graded-index (GI) square cores utilizing a ray tracing simulation. In this simulation, we focus on the index exponent values for the GI profile, which allows low crossing loss even if the number of crossing is as large as 50 or even if the crossing angle is as low as 20 degrees . It is revealed that an index exponent of 2.0 for the GI core strongly contributes to exhibit 35 times lower loss (0.072 dB after 50 perpendicular crosses) compared to the loss of the SI-core counterpart (2.58 dB after the same crossings). The GI cores with a smaller index exponent exhibit better loss in crossed waveguides with a wide range of crossing angles from 30 degrees to 90 degrees . Furthermore, we discuss the effect of the refractive index profile at the intersection on the optical loss of crossed waveguides. PMID- 26368199 TI - Defect states and exceptional point splitting in the band gaps of one-dimensional parity-time lattices. AB - We investigated defect states in band gaps of one-dimensional photonic lattices with delicate modulations of gain and loss that respect parity-time-symmetry (PT symmetry), viz. n(z) = n*(-z). For the sake of generality, we employ not only periodic structures but also quasiperiodic structures, e.g. Fibonacci sequences, to construct aperiodic PT lattices. Differed from lossless systems for which the defect state is related to only one exceptional point (EP) of the S-matrix, we observed the splitting of one EP into a pair after the introduction of judiciously designed gain and loss in those PT systems, where the defect state enters a non-threshold broken symmetry phase bounded by the EP pair. Some interesting properties associated with defect states and EP splitting are demonstrated, such as enhanced spectral localization, double optical phase abrupt change, and wavelength sensitive reversion of unidirectional transparency. PMID- 26368200 TI - Probe-controlled soliton frequency shift in the regime of optical event horizon. AB - In optical analogy of the event horizon, temporal pulse collision and mutual interactions are mainly between an intense solitary wave (soliton) and a dispersive probe wave. In such a regime, here we numerically investigate the probe-controlled soliton frequency shift as well as the soliton self-compression. In particular, in the dispersion landscape with multiple zero dispersion wavelengths, bi-directional soliton spectral tunneling effects is possible. Moreover, we propose a mid-infrared soliton self-compression to the generation of few-cycle ultrashort pulses, in a bulk of quadratic nonlinear crystals in contrast to optical fibers or cubic nonlinear media, which could contribute to the community with a simple and flexible method to experimental implementations. PMID- 26368201 TI - Semi-analytical modeling and parameterization of particulates-in-water phase function for forward angles. AB - A model based on Mie theory is described for predicting scattering phase functions at forward angles (0.1 degrees -90 degrees ) with particle size distribution (PSD) slope and bulk refractive index as input parameters. The PSD slope 'xi ' is calculated from the hyperbolic slope of the particle attenuation spectrum measured in different waters. The bulk refractive index 'n' is evaluated by an inversion model, using measured backscattering ratio (Bp) and PSD slope values. For predicting the desired phase function in a certain water type, in situ measurements of the coefficients of particulate backscattering, scattering and beam attenuation are needed. These parameters are easily measurable using commercially available instruments which provide data with high sampling rates. Thus numerical calculation of the volume scattering function is carried out extensively by varying the optical characteristics of particulates in water. The entire range of forward scattering angles (0.1 degrees -90 degrees ) is divided into two subsets, i.e., 0.1 degrees to 5 degrees and 5 degrees to 90 degrees . The particulates-in-water phase function is then modeled for both the ranges. Results of the present model are evaluated based on the well-established Petzold average particle phase function and by comparison with those predicted by other phase function models. For validation, the backscattering ratio is modeled as a function of the bulk refractive index and PSD slope, which is subsequently inverted to give a methodology to estimate the bulk refractive index from easily measurable optical parameters. The new phase function model which is based on the exact numerical solution obtained through Mie theory is mathematically less complex and predicts forward scattering phase functions within the desired accuracy. PMID- 26368203 TI - Statistical analysis of intrinsic and extrinsic coupling losses for step-index polymer optical fibers. AB - The intrinsic and extrinsic coupling losses of step-index polymer optical fibers are statistically examined by Monte Carlo simulations. In contrast to most existing models that linearly scale individual losses, a comprehensive analytic coupling loss model is used that also considers the interdependencies between mismatches in numerical aperture and core diameter, as well as radial and longitudinal offsets. As a typical example, the coupling losses of A4a.2 step index multimode fibers are analyzed for an equilibrium mode distribution. The results show considerably less conservative coupling loss estimations than with traditional models, improving link power budgeting. PMID- 26368202 TI - 3D fluorescence anisotropy imaging using selective plane illumination microscopy. AB - Fluorescence anisotropy imaging is a popular method to visualize changes in organization and conformation of biomolecules within cells and tissues. In such an experiment, depolarization effects resulting from differences in orientation, proximity and rotational mobility of fluorescently labeled molecules are probed with high spatial resolution. Fluorescence anisotropy is typically imaged using laser scanning and epifluorescence-based approaches. Unfortunately, those techniques are limited in either axial resolution, image acquisition speed, or by photobleaching. In the last decade, however, selective plane illumination microscopy has emerged as the preferred choice for three-dimensional time lapse imaging combining axial sectioning capability with fast, camera-based image acquisition, and minimal light exposure. We demonstrate how selective plane illumination microscopy can be utilized for three-dimensional fluorescence anisotropy imaging of live cells. We further examined the formation of focal adhesions by three-dimensional time lapse anisotropy imaging of CHO-K1 cells expressing an EGFP-paxillin fusion protein. PMID- 26368204 TI - Transient and steady-state entanglement mediated by three-dimensional plasmonic waveguides. AB - Entanglement between two qubits (two level atoms) mediated by surface plasmons in three-dimensional plasmonic waveguides is studied using a quantum master equation formalism. Two types of waveguides, a nanowire and a V-shaped channel cut in a flat metal plane, are considered. The Green functions for the waveguides, which rigorously describes the dissipative qubit environment, are calculated numerically using a direct finite-difference time-domain (FDTD) solution of Maxwell's equations. Finite-length effects are shown to play a crucial role in enhancing entanglement, and resonant-length plasmonic waveguides can provide higher entanglement between qubits than infinite-length waveguides. It is also shown that coupling slots can improve entanglement via stronger qubit-waveguide coupling, for both the infinite- and finite-waveguide cases. The formalism used in the paper can be applied to a wide range of plasmonic waveguides. PMID- 26368205 TI - Tunable superradiance and quantum phase gate based on graphene wrapped nanowire. AB - The interaction between quantum emitters and graphene wrapped nanowire has been investigated using a Green's function technique. The eigenmodes for the graphene wrapped nanowire at various Fermi levels in graphene have been solved exactly. The Dicke subradiance and superradiance resulting from the graphene-mediated interaction have been observed. Based on these phenomena, we have proposed a scheme for a deterministic tunable two-qubit quantum phase gate. The "switching" effect for the quantum phase gate has been realized theoretically by changing an external voltage, which is very beneficial for the quantum-information processing. PMID- 26368206 TI - Tunable Fe(2+):ZnSe passively Q-switched Ho(3+)-doped ZBLAN fiber laser around 3 MUm. AB - We report a tunable passively Q-switched Ho(3+)-doped ZBLAN fiber laser at 3 MUm waveband using a Fe(2+):ZnSe crystal as saturable absorber (SA) and a plane ruled grating in Littrow configuration as wavelength tuning element. Stable pulse trains with ~85 nm tuning range from 2919.1 nm to 3004.2 nm and spectrum bandwidths of ~1 nm were achieved for the Fe(2+):ZnSe crystal with an initial transmission (IT) of 69%. Pulse duration increased from 1.23 MUs to 2.35 MUs and repetition rate decreased from 96.1 kHz to 43.56 kHz with the extension towards long wavelength direction. With the IT increasing to 79% and then 89%, though the available tuning range was slightly shortened, higher output power, pulse energy and slope efficiency were obtained with the slightly increased pulse duration and repetition rate. Maximum output power of 337 mW at a slope efficiency of 11.44% and pulse energy of 5.64 MUJ were achieved at ~2970 nm and ~2991 nm, respectively. High signal noise ratio (SNR) of over 50 dB across the whole tuning range for the three ITs Fe(2+):ZnSe crystals indicated the stable Q-switching. To our knowledge, this is the first reported wavelength tunable passively Q-switched ZBLAN fiber laser. PMID- 26368207 TI - On the capacity of MISO FSO systems over gamma-gamma and misalignment fading channels. AB - In this work, the ergodic capacity performance for multiple-input/single-output (MISO) free-space optical (FSO) communications system with equal gain combining (EGC) reception is analyzed over gamma-gamma and misalignment fading channels, which are modeled as statistically independent, but not necessarily identically distributed (i.n.i.d.). Novel and analytical closed-form ergodic capacity expression is obtained in terms of H-Fox function by using the well-known inequality between arithmetic and geometric mean of positive random variables (RV) in order to obtain an approximate closed-form expression of the distribution of the sum of M gamma-gamma with pointing errors variates. In addition, we present an asymptotic ergodic capacity expression at high signal-to-noise ratio (SNR) for the ergodic capacity of MISO FSO systems. It can be concluded that the use of MISO technique can significantly reduce the effect of the atmospheric turbulence as well as pointing errors and, hence, provide significant capacity gain over the direct path link (DL). The impact of pointing errors on the MISO FSO system is also analyzed, which only depends on the number of laser sources and pointing error parameters. Moreover, it can be also concluded that the ergodic capacity performance is dramatically reduced as a consequence of the severity of pointing error effects. Simulation results are further demonstrated to confirm the analytical results. PMID- 26368208 TI - Laser phase and frequency noise measurement by Michelson interferometer composed of a 3 * 3 optical fiber coupler. AB - A laser phase and frequency noise measurement method by an unbalanced Michelson interferometer composed of a 3 * 3 optical fiber coupler is proposed. The relations and differences of the power spectral density (PSD) of differential phase and frequency fluctuation, PSD of instantaneous phase and frequency fluctuation, phase noise and linewidth are derived strictly and discussed carefully. The method obtains the noise features of a narrow linewidth laser conveniently without any specific assumptions or noise models. The technique is also used to characterize the noise features of a narrow linewidth external cavity semiconductor laser, which confirms the correction and robustness of the method. PMID- 26368209 TI - Optical transmission between III-V chips on Si using photonic wire bonding. AB - Photonic wire bonding (PWB) was used to achieve flexible chip-scale optical interconnection as a kind of 3D-freeform polymer waveguide based on the two photon polymerization of SU-8. First, the fabrication conditions of PWB were determined for the two-photon absorption process, and the coupling structure between PWB and III-V optical components was numerically simulated in order to obtain high coupling efficiency. Then, using PWB, chip-to-chip optical transmission was realized between laser and detector chips located on a common Si substrate. We fabricated a 2.5-MUm-wide PWB with 1:3 aspect ratio between two optical chips of 140-MUm gap and achieved a connection loss of approximately 10 dB. PMID- 26368210 TI - Fitting discrete aspherical surface sag data using orthonormal polynomials. AB - Characterizing real-life optical surfaces usually involves finding the best-fit of an appropriate surface model to a set of discrete measurement data. This process can be greatly simplified by choosing orthonormal polynomials for the surface description. In case of rotationally symmetric aspherical surfaces, new sets of orthogonal polynomials were introduced by Forbes to replace the numerical unstable standard description. From these, for the application of surface retrieval using experimental ray tracing, the sag orthogonal Q(con)-polynomials are of particular interest. However, these are by definition orthogonal over continuous data and may not be orthogonal for discrete data. In this case, the simplified solution is not valid. Hence, a Gram-Schmidt orthonormalization of these polynomials over the discrete data set is proposed to solve this problem. The resulting difference will be presented by a performance analysis and comparison to the direct matrix inversion method. PMID- 26368211 TI - Waveguide-coupled micro-ball lens array suitable for mass fabrication. AB - We demonstrate a fabrication procedure for the direct integration of micro-ball lenses on planar integrated optical channel waveguide chips with the aim to reduce the divergence of light that arises from the waveguide in both horizontal and vertical directions. Fabrication of the lenses is based on photoresist reflow which is a procedure that allows for the use of photolithography for careful alignment of the lenses with respect to the waveguides and enables mass production. We present in detail the design and fabrication procedures. Optical characterization of the fabricated micro-ball lenses demonstrates a good performance in terms of beam-size reduction and beam shape. The beam half divergence angle of 1544 nm light is reduced from 12.4 degrees to 1.85 degrees . PMID- 26368212 TI - Investigation of germanium quantum-well light sources. AB - In this paper, we report a broad investigation of the optical properties of germanium (Ge) quantum-well devices. Our simulations show a significant increase of carrier density in the Ge quantum wells. Photoluminescence (PL) measurements show the enhanced direct-bandgap radiative recombination rates due to the carrier density increase in the Ge quantum wells. Electroluminescence (EL) measurements show the temperature-dependent properties of our Ge quantum-well devices, which are in good agreement with our theoretical models. We also demonstrate the PL measurements of Ge quantum-well microdisks using tapered-fiber collection method and quantify the optical loss of the Ge quantum-well structure from the measured PL spectra for the first time. PMID- 26368213 TI - Highly efficient chip-scale III-V/silicon hybrid optical amplifiers. AB - We discuss the design and demonstration of highly efficient 1.55 um hybrid III V/Silicon semiconductor optical amplifiers (SOA). The optimized III-V wafer stack consists of Al(0.10)In(0.71)Ga(0.18)As multiple quantum wells (MQW) and Al(0.48)In(0.52)As electron stop layers to realize SOAs with high wall-plug efficiency (WPE). We present various designs and experimentally determine WPE values for 2 mW and 0.1 mW input power amplification. The 400 um long flared SOA achieved the highest WPE value of 12.1% for output power > 10mW and the 400 um long straight SOA achieved the highest WPE value of 7.3% for output power < 10mW. These are the highest WPE values ever obtained for 1.55 um SOAs. PMID- 26368214 TI - Evaluation of optical arrangements for ballistic imaging in sprays. AB - This work investigates the imaging performance, in terms of contrast and resolution, of two different time-gated ballistic imaging setups commonly used in spray research. It is shown that the two setups generate similar spatial resolution in the presence of scattering media. The simpler (2f) setup, however, is less sensitive to component misalignments and time-gate induced aberrations than the commonly used (4f) system. Measurements comparing both arrangements indicated slightly higher contrast for the 2f system under the densest conditions for small scatterers. Subsequent computational modeling confirmed the observed tolerance of the 2f system to misalignment and gate effects. The best performing setup was also compared experimentally to its non-time-gated shadow-imaging equivalent, to establish when the time-gate enhances imaging performance. It is shown that the time-gated setup generates higher contrast under almost all of the scattering conditions tested, while the non-time-gated setup generates higher spatial resolution only in the lower scatterer size range at the lowest scatterer concentrations. PMID- 26368215 TI - Cascade Raman sideband generation and orbital angular momentum relations for paraxial beam modes. AB - In this work, the nonlinear parametric interaction of optical radiation in various transverse modes in a Raman-active medium is investigated both experimentally and theoretically. Verification of the orbital angular momentum algebra (OAM-algebra) [Strohaber et al.,Opt. Lett.37,3411 (2012)] was performed for high-order Laguerre Gaussian modes l>1. It was found that this same algebra also describes the coherent transfer of OAM when Ince-Gaussian modes were used. New theoretical considerations extend the OAM-algebra to even and odd Laguerre Gaussian, and Hermite Gaussian beam modes through a change of basis. The results of this work provide details in the spatiotemporal synthesis of custom broadband pulses of radiation from Raman sideband generation. PMID- 26368216 TI - Tuneable four-wave mixing in AlGaAs nanowires. AB - We have experimentally demonstrated broadband tuneable four-wave mixing in AlGaAs nanowires with the widths ranging between 400 and 650 nm and lengths from 0 to 2 mm. We performed a detailed experimental study of the parameters influencing the FWM performance in these devices (experimental conditions and nanowire dimensions). The maximum signal-to-idler conversion range was 100 nm, limited by the tuning range of the pump source. The maximum conversion efficiency, defined as the ratio of the output idler power to the output signal power, was -38 dB. In support of our explanation of the experimentally observed trends, we present modal analysis and group velocity dispersion numerical analysis. This study is what we believe to be a step forward towards realization of all-optical signal processing devices. PMID- 26368217 TI - Development of a fan-beam TDLAS-based tomographic sensor for rapid imaging of temperature and gas concentration. AB - This work aims to develop a fan-beam tomographic sensor using tunable diode lasers that can simultaneously image temperature and gas concentration with both high spatial and temporal resolutions. The sensor features three key advantages. First, the sensor bases on a stationary fan-beam arrangement, by which a high spatial resolution is guaranteed because the distance between two neighboring detectors in a view is approximately reduced to the size of a photodiode. Second, fan-beam illumination from five views is simultaneously generated instead of rotating either the fanned beams or the target, which significantly enhances the temporal resolution. Third, a novel set of optics with the combination of anamorphic prism pair and cylindrical lens is designed, which greatly improves the uniformity of the planar beams, and hence improves the reconstruction fidelity. This paper reports the tomographic model, optics design, numerical simulation and experimental validation of the sensor. The sensor exhibits good applicability for flame monitoring and combustion diagnosis. PMID- 26368218 TI - Dynamic control of optical transmission through a nano-slit using surface plasmons. AB - We demonstrate how the optical transmission by a directly illuminated, sub wavelength slit in a metal film can be dynamically controlled by varying the incident beam's phase relative to that of a stream of surface plasmon polaritions which are generated at a nearby grating. The transmission can be smoothly altered from its maximum value to practically zero. The results from a simple model and from rigorous numerical simulations are in excellent agreement with our experimental results. Our method may be applied in all-optical switching. PMID- 26368219 TI - All-optical light storage in bound states in the continuum and release by demand. AB - In the framework of the temporal coupled mode theory we consider bound states embedded in the continuum (BSC) of photonic crystal waveguide as a capacity for light storage. A symmetry protected BSC occurs in two off-channel microresonators positioned symmetrically relative to the waveguide. We demonstrate that the symmetry protected BSC captures a fraction of a light pulse due to the Kerr effect as the pulse passes by the microresonators. However the amount of captured light is found to be strongly sensitive to the parameters of the gaussian light pulse such as basic frequency, duration and intensity. In contrast to the above case the BSC resulted from a full destructive interference of two eigenmodes of a single microresonator accumulates a fixed amount of light dependent on the material parameters of the microresonator but independent of the light pulse. The BSCs in the Fabry-Perot resonator show similar effects. We also show that the accumulated light can be released by a secondary pulse. These phenomena pave a way for all-optical storage and release of light. PMID- 26368220 TI - Flexible photonic components in glass substrates. AB - This paper demonstrates the fabrication and measurements of flexible photonic lightwave circuits in glass substrates. Using temporally and spatially shaped ultrafast laser pulses, highly symmetrical and low-loss optical waveguides were written in flexible glass substrates with thicknesses ranging from 25 um to 100 um. The waveguide propagation loss, measured by optical frequency domain reflectometry, was 0.11 dB/cm at 1550 nm telecommunication wavelength. The bend loss of the waveguide is negligible at a radius of curvature of 1.5 cm or greater. Additionally, the waveguides are thermally stable up to 400 degrees C. This paper presents alternatives to fabricating flexible photonics in traditionally used polymeric materials. PMID- 26368221 TI - Fourier transform analysis of hexagonal domain for transparent conductive graphene. AB - In this paper, we applied the Fourier Transformation as a notion to calculate the orientation of hexagonal graphene domains on Cu substrate. We developed that a hexagon function to describe the diffraction pattern of hexagonal graphene. Hexagonal graphene domains grown on Cu (111) has an average value of orientation surrounding 3 degrees in the frequency domain. For transparent conducting electrode applications, optical and electrical properties of large-area graphene film (2cm(2)) was measured. The results demonstrate that graphene grown on Cu (111) was greater than graphene grown on polycrystalline Cu. PMID- 26368222 TI - Broadband polarization independent nanophotonic coupler for silicon waveguides with ultra-high efficiency. AB - Coupling of light to and from integrated optical circuits has been recognized as a major practical challenge since the early years of photonics. The coupling is particularly difficult for high index contrast waveguides such as silicon-on insulator, since the cross-sectional area of silicon wire waveguides is more than two orders of magnitude smaller than that of a standard single-mode fiber. Here, we experimentally demonstrate unprecedented control over the light coupling between the optical fiber and silicon chip by constructing the nanophotonic coupler with ultra-high coupling efficiency simultaneously for both transverse electric and transverse magnetic polarizations. We specifically demonstrate a subwavelength refractive index engineered nanostructure to mitigate loss and wavelength resonances by suppressing diffraction effects, enabling a coupling efficiency over 92% (0.32 dB) and polarization independent operation for a broad spectral range exceeding 100 nm. PMID- 26368223 TI - Direct laser writing of pyramidal plasmonic structures with apertures and asymmetric gratings towards efficient subwavelength light focusing. AB - Efficient confining of photons into subwavelength scale is of great importance in both fundamental researches and engineering applications, of which one major challenge lies in the lack of effective and reliable on-chip nanofabrication techniques. Here we demonstrate the efficient subwavelength light focusing with carefully engineered pyramidal structures fabricated by direct laser writing and surface metallization. The important effects of the geometry and symmetry are investigated. Apertures with various sizes are flexibly introduced at the apex of the pyramids, the focusing spot size and center-to-sidelobe ratio of which could be improved a factor of ~4 and ~3, respectively, compared with the conical counterparts of identical size. Moreover, two pairs of asymmetric through nanogratings are conceptually introduced onto the top end of the pyramids, showing significantly improved focusing characteristics. The studies provide a novel methodology for the design and realization of 3D plasmonic focusing with low-noise background and high energy transfer. PMID- 26368224 TI - Bit rate transparent interferometric noise mitigation utilizing the nonlinear modulation curve of electro-absorption modulator. AB - we propose a bit-rate transparent interferometric noise mitigation scheme utilizing the nonlinear modulation curve of electro-absorption modulator (EAM). Both the zero-slope region and the linear modulation region of the nonlinear modulation curve are utilized to suppress interferometric noise and enlarge noise margin of degraded eye diagrams. Using amplitude suppression effect of the zero slope region, interferometric noise at low frequency range is suppressed successfully. Under different signal to noise ratio (SNR), we measured the power penalties at bit error rate (BER) of 10<(-9) with and without EAM interferometric noise suppression. By using our proposed scheme, power penalty improvement of 8.5 dB is achieved in a signal with signal-to-noise ratio of 12.5 dB. BER results at various bit rates are analyzed, error floors for each BER curves are removed, significantly improvement in receiver sensitivity and widely opened eye diagrams are resulted. PMID- 26368225 TI - Tracking of colloids close to contact. AB - The precise tracking of micron sized colloidal particles - held in the vicinity of each other using optical tweezers - is an elegant way to gain information about the particle-particle pair interaction potential. The accuracy of the method, however, relies strongly on the tracking precision. Particularly the elimination of systematic errors in the position detection due to overlapping particle diffraction patterns remains a great challenge. Here we propose a template based particle finding algorithm that circumvents these problems by tracking only a fraction of the particle image that is insignificantly affected by nearby colloids. Under realistic experimental conditions we show that our algorithm significantly reduces systematic errors compared to standard tracking methods. Moreover our approach should in principle be applicable to almost arbitrary shaped particles as the template can be adapted to any geometry. PMID- 26368226 TI - Elliptical metallic hollow fiber inner-coated with non-uniform dielectric layer. AB - We report on the fabrication and characterization of an elliptical hollow fiber inner coated with a silver layer and a dielectric layer for polarization maintaining and low loss transmission of terahertz (THz) radiation. The primary purpose of adding the dielectric layer is to prevent the silver layer from oxidation. The thickness of the dielectric layer is non-uniform owing to the surface tension of the coating, which was initially applied as a liquid. Transmission loss and polarization maintenance are experimentally characterized. Effects of the dielectric layer on transmission properties are analyzed by comparing the fiber to Ag-only fiber. Results show that a dielectric layer with thickness less than lambda/10 can effectively decreases the power distributed on the metal surface and thus can practically reduce loss resulting from roughness of the silver layer. Bending effects on transmission loss and polarization maintenance are also investigated. PMID- 26368227 TI - Nanocomposites with gold nanorod/silica core-shell structure as saturable absorber for femtosecond pulse generation in a fiber laser. AB - Ultrafast fiber lasers play a significant role in our society with many aspects ranging from fundamental physics to industrial purposes. Searching for high performance saturable absorbers (SAs) is vital to the developments of ultrafast fiber lasers. Gold nanorods (GNRs) have been discovered to possess saturable absorption effect. However, a major obstacle to make the GNRs as high-performance and practical SA is the low optical damage threshold. To overcome this drawback, herein we proposed the nanocomposites with gold nanorods/silica core-shell structure (GNRs@SiO(2)) as a high-performance SA for ultrashort pulse generation in a fiber laser. The GNRs@SiO(2) SA presents a modulation depth of 4.2% and nonsaturable loss of 45.6%. With the proposed GNRs@SiO(2) SA, 379 fs pulse was directly obtained from the fiber laser. The achieved results demonstrated that the GNR@SiO(2) could be indeed a good candidate of high-performance SA towards practical applications in the field of ultrafast photonics. PMID- 26368228 TI - Polarization selective beam shaping using nanoscale dielectric metasurfaces. AB - Metasurfaces consisting of ultrathin nanostructures are utilized to control the properties of light including its phase, amplitude and polarization. Hereby, we demonstrate the capability of such structures to perform arbitrary polarization selective beam shaping using dielectric nanoscale metasurfaces implemented in silicon. By illuminating the structure with right handed circular polarization we reconstruct a desired image. When switching the polarization into its orthogonal state, we obtain the reconstruction of a different image. This demonstration shows the potential of using dielectric metasurfaces for high efficiency beam shaping applications in general, and specifically for polarization coded beam shaping. PMID- 26368229 TI - General coupled mode theory in non-Hermitian waveguides. AB - In the presence of loss and gain, the coupled mode equation on describing the mode hybridization of various waveguides or cavities, or cavities coupled to waveguides becomes intrinsically non-Hermitian. In such non-Hermitian waveguides, the standard coupled mode theory fails. We generalize the coupled mode theory with a properly defined inner product based on reaction conservation. We apply our theory to the non-Hermitian parity-time symmetric waveguides, and obtain excellent agreement with results obtained by finite element fullwave simulations. The theory presented here is typically formulated in space to study coupling between waveguides, which can be transformed into time domain by proper reformulation to study coupling between non-Hermitian resonators. Our theory has the strength of studying non-Hermitian optical systems with inclusion of the full vector fields, thus is useful to study and design non-Hermitian devices that support asymmetric and even nonreciprocal light propagations. PMID- 26368230 TI - Subwavelength index engineered surface grating coupler with sub-decibel efficiency for 220-nm silicon-on-insulator waveguides. AB - Surface grating couplers are fundamental components in chip-based photonic devices to couple light between photonic integrated circuits and optical fibers. In this work, we report on a grating coupler with sub-decibel experimental coupling efficiency using a single etch process in a standard 220-nm silicon-on insulator (SOI) platform. We specifically demonstrate a subwavelength metamaterial refractive index engineered nanostructure with backside metal reflector, with the measured peak fiber-chip coupling efficiency of -0.69 dB (85.3%) and 3 dB bandwidth of 60 nm. This is the highest coupling efficiency hitherto experimentally achieved for a surface grating coupler implemented in 220 nm SOI platform. PMID- 26368231 TI - Polymer stabilization of electrohydrodynamic instability in non-iridescent cholesteric thin films. AB - A non-iridescent cholesterol liquid crystal (CLC) thin film is demonstrated by using the polymer-stabilized electrohydrodymanic (PSEHD) method. The photopolymerized cell made from a CLC/monomer mixture exhibits an optically stable gridlike pattern. The helical axis of thus-formed CLC is aligned with the hydrodynamic flow induced by a space charge motion, and the arrayed CLC grid configuration renders a wide viewing angle thanks to the limited color shift at various lines of sight. The formation of the PSEHD structure was verified with polarized optical microscopy, ascertaining that the electrohydrodymanic pattern can be photo-cured or stabilized. The PSEHD CLC is simple to fabricate and potentially suitable for applications in wide-viewing-angle or non-iridescent devices. PMID- 26368232 TI - Few-layer black phosphorus based saturable absorber mirror for pulsed solid-state lasers. AB - We experimentally demonstrated that few-layer black phosphorus (BP) could be used as an optical modulator for solid-state lasers to generate short laser pulses. The BP flakes were fabricated by the liquid phase exfoliation method and drop casted on a high-reflection mirror to form a BP-based saturable absorber mirror (BP-SAM). Stable Q-switched pulses with a pulse width of 620 ns at the wavelength of 1046 nm were obtained in a Yb:CaYAlO(4) (Yb:CYA) laser with the BP-SAM. The generated pulse train has a repetition rate of 113.6 kHz and an average output power of 37 mW. Our results show that the BP-SAMs could have excellent prospective for ultrafast photonics applications. PMID- 26368233 TI - Fourier multispectral imaging. AB - Current multispectral imaging systems use narrowband filters to capture the spectral content of a scene, which necessitates different filters to be designed for each application. In this paper, we demonstrate the concept of Fourier multispectral imaging which uses filters with sinusoidally varying transmittance. We designed and built these filters employing a single-cavity resonance, and made spectral measurements with a multispectral LED array. The measurements show that spectral features such as transmission and absorption peaks are preserved with this technique, which makes it a versatile technique than narrowband filters for a wide range of multispectral imaging applications. PMID- 26368234 TI - Photo-induced handedness inversion with opposite-handed cholesteric liquid crystal. AB - Cholesteric liquid crystals (CLCs) are self-organized helical nano-structures that selectively reflect certain wavelength of a circularly polarized light. For most CLCs, the handedness is fixed once a chiral dopant is employed. Here, we report a handedness-invertible CLC through opposite-handed doping of a photo sensitive chiral azobenzene dopant and a photo-stable chiral dopant. With high solubility of the photo-sensitive chiral dopant, the Bragg reflection can be tailored from right-handed to left-handed upon UV exposure. The reversed process can be easily carried out through heating. PMID- 26368235 TI - 3D super-resolved in vitro multiphoton microscopy by saturation of excitation. AB - We demonstrate a significant resolution enhancement beyond the conventional limit in multiphoton microscopy (MPM) using saturated excitation of fluorescence. Our technique achieves super-resolved imaging by temporally modulating the excitation laser-intensity and demodulating the higher harmonics from the saturated fluorescence signal. The improvement of the lateral and axial resolutions is measured on a sample of fluorescent microspheres. While the third harmonic already provides an enhanced resolution, we show that a further improvement can be obtained with an appropriate linear combination of the demodulated harmonics. Finally, we present in vitro imaging of fluorescent microspheres incorporated in HeLa cells to show that this technique performs well in biological samples. PMID- 26368236 TI - TO-56-can packaged colorless WRC-FPLD for QAM OFDM transmission at 42 Gbit/s over 25-km SMF. AB - The weak-resonant-cavity Fabry-Perot laser diode (WRC-FPLD) with colorless and channelized mode features is a new-class optical transmitter fulfilling the need of next-generation communications. By packaging the colorless WRC-FPLD transmitter with a 10-GHz transistor-outline-56-can (TO-56-can), the premier demonstration on directly modulated 42-Gbit/s/channel quadrature amplitude modulation (QAM) orthogonal frequency division multiplexing (OFDM) transmission is demonstrated via wavelength injection-locking. Enlarging the injection level effectively up-shifts the relaxation oscillation peak and suppresses the relative intensity noise, which facilitates the TO-56-can packaged WRC-FPLD to improve its modulation throughput bandwidth to 9 GHz and enhance its signal-to-noise ratio to 22 dB. By pre-amplifying the directly modulated QAM-OFDM data with a total raw bit rate of 42 Gbit/s, the receiving bit-error-rate (BER) under back-to-back transmission can be reduced below the forward-error-correction (FEC) limited BER of 3.8 * 10(-3). Such a colorless WRC-FPLD enables the QAM-OFDM transmission over a 25-km long single-mode-fiber based metropolitan access network with its BER matching the FEC criterion at a receiving power of -2 dBm. PMID- 26368237 TI - Remote heterodyne millimeter-wave over fiber based OFDM-PON with master-to-slave injected dual-mode colorless FPLD pair. AB - A remote heterodyne millimeter-wave (MMW) carrier at 47.7 GHz over fiber synthesized with the master-to-slave injected dual-mode colorless FPLD pair is proposed, which enables the future connection between the wired fiber-optic 64 QAM OFDM-PON at 24 Gb/s with the MMW 4-QAM OFDM wireless network at 2 Gb/s. Both the single- and dual-mode master-to-slave injection-locked colorless FPLD pairs are compared to optimize the proposed 64-QAM OFDM-PON. For the unamplified single mode master, the slave colorless FPLD successfully performs the 64-QAM OFDM data at 24 Gb/s with EVM, SNR and BER of 8.5%, 21.5 dB and 2.9 * 10(-3), respectively. In contrast, the dual-mode master-to-slave injection-locked colorless FPLD pair with amplified and unfiltered master can transmit 64-QAM OFDM data at 18 Gb/s over 25-km SMF to provide EVM, SNR and BER of 8.2%, 21.8 dB and 2.2 * 10(-3), respectively. For the dual-mode master-to-slave injection-locked colorless FPLD pair, even though the modal dispersion occurred during 25-km SMF transmission makes it sacrifice the usable OFDM bandwidth by only 1 GHz, which guarantees the sufficient encoding bitrate for the optically generated MMW carrier to implement the fusion of MMW wireless LAN and DWDM-PON with cost-effective and compact architecture. As a result, the 47.7-GHz MMW carrier remotely beat from the dual mode master-to-slave injection-locked colorless FPLD pair exhibits an extremely narrow bandwidth of only 0.48 MHz. After frequency down-conversion operation, the 47.7-GHz MMW carrier successfully delivers 4-QAM OFDM data up to 2 Gb/s with EVM, SNR and BER of 33.5%, 9.51 dB and 1.4 * 10(-3), respectively. PMID- 26368238 TI - Ultra-dense WDM-PON 6.25 GHz spaced 8*1 Gb/s based on a simplified coherent detection scheme. AB - We demonstrate experimentally a novel type of coherent low cost Gigabit-to-the User Ultra-Dense-Wavelength Division Multiplexing (UD-WDM) PON, featuring 6.25 GHz channel spacing and long reach. Polarization-independent coherent detection is achieved by exploiting a novel scheme which requires only a 3 * 3 coupler, three photodiodes, basic analogue processing and a common DFB as local oscillator (LO). This avoids the conventional polarization diversity approach. The DFB LO is free running, i.e. not locked in frequency, and is tuned to detect any of the eight channels by simply changing its temperature in a range of 2 degrees C. We achieve 70 km long-reach transmission plus 30 dB attenuation, for a total of > 45 dB optical distribution network loss. This indicates that this solution could be effectively exploited to overlay existing PON infrastructures by UD-WDM. PMID- 26368239 TI - Bend-insensitive distributed sensing in singlemode-multimode-singlemode optical fiber structure by using Brillouin optical time-domain analysis. AB - We propose a bend-insensitive distributed Brillouin optical fiber sensing by using a singlemode-multimode-singlemode optical fiber structure for the first time to the best of our knowledge. The sensing fiber is a graded-index multimode fiber (GI-MMF) sandwiched by two standard single-mode fibers (SMFs) with central alignment splicing at the interface between GI-MMF and SMF to excite the fundamental mode in GI-MMF. The sensing system can resist a minimal bend radius of 1.25mm while maintain the measurement performance, with which the measured coefficients of strain and temperature are 421.6MHz/% and 0.826MHz/ degrees C, respectively. We also demonstrate that the higher-order modes excited in GI-MMF can be easily influenced by bending, so that exciting the fundamental mode is essential for bend-insensitive distributed sensing. PMID- 26368240 TI - Tunable multi-cycle THz generation in organic crystal HMQ-TMS. AB - We report on the generation of continuously tunable multi-cycle THz pulses with center frequencies from 0.3 to 0.8 THz in the organic nonlinear crystal, HMQ-TMS [2-(4-hydroxy-3-methoxystyryl)-1-methylquinolinium 2,-4,-6 trimethylbenzenesulfonate], by collinearly phase matched optical rectification of temporally shaped 800 nm pulses. The generation of harmonic frequency components inherent in the pulse shaper is selectively suppressed by varying the generation crystal thickness. THz pulses generated from HMQ-TMS show up to 20 times higher pulse energies compared to the benchmark inorganic THz generator ZnTe under identical conditions. The THz energy conversion efficiencies are measured to be on the order of 10(-5). PMID- 26368241 TI - Conical photonic crystals for enhancing light extraction efficiency from high refractive index materials. AB - We propose, analyze and optimize a two-dimensional conical photonic crystal geometry to enhance light extraction from a high refractive index material, such as an inorganic scintillator. The conical geometry suppresses Fresnel reflections at an optical interface due to adiabatic impedance matching from a gradient index effect. The periodic array of cone structures with a pitch larger than the wavelength of light diffracts light into higher-order modes with different propagating angles, enabling certain photons to overcome total internal reflection (TIR). The numerical simulation shows simultaneous light yield gains relative to a flat surface both below and above the critical angle and how key parameters affect the light extraction efficiency. Our optimized design provides a 46% gain in light yield when the conical photonic crystals are coated on an LSO (cerium-doped lutetium oxyorthosilicate) scintillator. PMID- 26368242 TI - Mode-selective lasing in high-Q polymer micro bottle resonators. AB - Passive and active polymer micro bottle resonators (MBRs) are fabricated. Equatorial whispering gallery modes and bottle modes are clearly identified, with highest loaded quality (Q) factor above 10(5). Lasing with threshold as low as 1 nJ/pulse is realized in active MBRs. Mode selective lasing is achieved by coupling a tapered fiber to equatorial whispering gallery modes or a group of bottle modes. The bottle mode free spectral range (FSR) is found to be about one fifth of the equatorial modes. PMID- 26368243 TI - Heterogeneous microring and Mach-Zehnder modulators based on lithium niobate and chalcogenide glasses on silicon. AB - Thin films of lithium niobate are wafer bonded onto silicon substrates and rib loaded with a chalcogenide glass, Ge(23)Sb(7)S(70), to demonstrate strongly confined single-mode submicron waveguides, microring modulators, and Mach-Zehnder modulators in the telecom C band. The 200 MUm radii microring modulators present 1.2 dB/cm waveguide propagation loss, 1.2 * 10(5) quality factor, 0.4 GHz/V tuning rate, and 13 dB extinction ratio. The 6 mm long Mach-Zehnder modulators have a half-wave voltage-length product of 3.8 V.cm and an extinction ratio of 15 dB. The demonstrated work is a key step towards enabling wafer scale dense on chip integration of high performance lithium niobate electro-optical devices on silicon for short reach optical interconnects and higher order advanced modulation schemes. PMID- 26368244 TI - On symmetric X-ray beam splitting with high efficiency by use of reflection gratings with rectangular profile in the extreme off-plane configuration. AB - In order to be reflected or diffracted off a surface structure soft X-rays and hard X-rays need to impinge at grazing angles of incidence onto the surface. In case of a reflection grating of highly symmetric structure with rectangular groove profile these grooves can be oriented parallel to the beam trajectory. In such a symmetric situation the distribution of the diffracted intensity with respect to the plane of incidence is then expected to be symmetric. This is indeed observed with symmetrically oriented diffraction peaks. It can be predicted that for appropriate structure parameters the intensity can be contained mostly in two symmetrically oriented diffraction peaks. This will also be the case for hard X-rays. The diffraction efficiency will be particularly high, when the angle of grazing incidence is chosen in the total reflection regime below the critical angle of the grating coating. These predictions were experimentally verified in this work for hard X-rays with photon energies between 4 keV and 12.4 keV. In the experiment of the order of 30% of the incident intensity was diffracted into the two first orders. This is to be compared to reflectivities of the order of 50% measured at the same coating in an unruled area of the substrate. Consequently the relative structural diffraction efficiency for each first order was about 30%, while ideally it could have been 40%. The presented grating structure will thus be a rather efficient amplitude beam splitter for hard X-rays, e.g. in the coherent beam from a free electron laser. In addition such object could then be used as the first component in Michelson interferometers for the beam characterisation or for introducing a time delay between two coherent beams. PMID- 26368245 TI - Intracavity continuous-wave multiple stimulated-Raman-scattering emissions in a KTP crystal pumped by a Nd:YVO(4) laser. AB - Intracavity continuous-wave (CW) multiple stimulated-Raman-scattering emissions have been successfully demonstrated in a KTP crystal pumped by a Nd:YVO(4) 1064 nm laser for the first time. Three different output couplers (OCs) with high reflection (HR) coating in the range of 1-1.1, 1-1.13, and 1-1.15 MUm are employed in the experiment to generate lasing wavelengths at 1095 (the first Stokes emission of the 266 cm(-1) Raman shift), 1095 + 1128 (the first- and second-Stokes emission of the 266 cm(-1) Raman shift), and 1095 + 1128 + 1149 nm (the first two Stokes emissions of the 266 cm(-1) Raman shift and the first Stokes emission of the 694 cm(-1) Raman shift), separately. This Raman laser paves a way to produce more-closely spaced set of CW emission in the green-yellow region. PMID- 26368246 TI - Antenna resonances in low aspect ratio semiconductor nanowires. AB - We present numerical simulations of low aspect ratio gallium phosphide nanowires under plane wave illumination, which reveal the interplay between transverse and longitudinal antenna-like resonances. A comparison to the limiting case of the semiconducting sphere shows a gradual, continuous transition of resonant electric and magnetic spherical Mie modes into Fabry-Perot cavity modes with mixed electric and magnetic characteristics. As the length of the nanowires further increases, these finite-wire modes converge towards the leaky-mode resonances of an infinite cylindrical wire. Furthermore, we report a large and selective enhancement or suppression of electric and magnetic field in structures comprising two semiconducting nanowires. For an interparticle separation of 20 nm, we observe up to 300-fold enhancement in the electric field intensity and an almost complete quenching of the magnetic field in specific mode configurations. Angle-dependent extinction spectra highlight the importance of symmetry and phase matching in the excitation of cavity modes and show the limited validity of the infinite wire approximation for describing the response of finite length nanowires toward glancing angles. PMID- 26368247 TI - Modified polarized geometrical attenuation model for bidirectional reflection distribution function based on random surface microfacet theory. AB - The geometrical attenuation model given by Blinn was widely used in the geometrical optics bidirectional reflectance distribution function (BRDF) models. Blinn's geometrical attenuation model based on symmetrical V-groove assumption and ray scalar theory causes obvious inaccuracies in BRDF curves and negatives the effects of polarization. Aiming at these questions, a modified polarized geometrical attenuation model based on random surface microfacet theory is presented by combining of masking and shadowing effects and polarized effect. The p-polarized, s-polarized and unpolarized geometrical attenuation functions are given in their separate expressions and are validated with experimental data of two samples. It shows that the modified polarized geometrical attenuation function reaches better physical rationality, improves the precision of BRDF model, and widens the applications for different polarization. PMID- 26368248 TI - Dispersion of polarization coupling, localized and collective plasmon modes in a metallic photonic crystal mapped by Mueller Matrix Ellipsometry. AB - We report a spectroscopic Mueller matrix experimental study of a plasmonic photonic crystal consisting of gold hemispheroidal particles (lateral radius 54 nm, height 25 nm) arranged on a square lattice (lattice constant 210 nm) and supported by a glass substrate. Strong polarization coupling is observed for ultraviolet wavelengths and around the surface plasmon resonance for which the off-block-diagonal Mueller matrix elements show pronounced anisotropies. Due to the Rayleigh anomalies, the block-diagonal Mueller matrix elements produce a direct image of the Brillouin Zone (BZ) boundaries of the lattice and resonances are observed at the M-point in the first and at the X-point in the second BZ. These elements show also the dispersion of the localized surface plasmon resonance. PMID- 26368249 TI - Integrated optic current transducers incorporating photonic crystal fiber for reduced temperature dependence. AB - Optical current transducers (OCT) are indispensable for accurate monitoring of large electrical currents in an environment suffering from severe electromagnetic interference. Temperature dependence of OCTs caused by its components, such as wave plates and optical fibers, should be reduced to allow temperature independent operation. A photonic crystal fiber with a structural optical birefringence was incorporated instead of a PM fiber, and a spun PM fiber was introduced to overcome the temperature-dependent linear birefringence of sensing fiber coil. Moreover, an integrated optic device that provides higher stability than fiber-optics was employed to control the polarization and detect the phase of the sensed optical signal. The proposed OCT exhibited much lower temperature dependence than that from a previous study. The OCT satisfied the 0.5 accuracy class (IIEC 60044-8) and had a temperature dependence less than +/- 1% for a temperature range of 25 to 78 degrees C. PMID- 26368250 TI - Self-compensated microstructure fiber optic sensor to detect high hydrogen concentration. AB - Dual-cavity microstructure fiber optic hydrogen sensor based on evaporated Pt/WO(3) film was proposed and experimentally explored in this paper, which provides a novel solution to detect high hydrogen concentration (10-30% H(2)). Dual-cavity microstructure fabricated by splicer is composed of an inner air cavity and a collapsed photonic crystal fiber cavity. The proposed sensor has the advantages of miniature structure, stable configuration, low cost. Based on three beam interference model and verification experiments, the compensation function to the fluctuation of light source and fiber loss is proved from the theoretical simulation and experimental investigation. The sensor has a short response time (1min), good repeatability and reliability. Besides, the change of temperature affects the response value of the hydrogen sensor, but the impact can be neglected in 10-30% H(2). PMID- 26368251 TI - Gilmore-Perelomov symmetry based approach to photonic lattices. AB - We revisit electromagnetic field propagation through tight-binding arrays of coupled photonic waveguides, with properties independent of the propagation distance, and recast it as a symmetry problem. We focus our analysis on photonic lattices with underlying symmetries given by three well-known groups, SU(2), SU(1, 1) and Heisenberg-Weyl, to show that disperssion relations, normal states and impulse functions can be constructed following a Gilmore-Perelomov coherent state approach. Furthermore, this symmetry based approach can be followed for each an every lattice with an underlying symmetry given by a dynamical group. PMID- 26368252 TI - All-optical wavelength conversion based on time-domain holography. AB - All-optical wavelength conversion of a complex (amplitude and phase) optical signal is proposed based on an all-optical implementation of time-domain holography. The temporal holograms are generated through a cross-phase modulation (XPM) process in a highly-nonlinear optical fiber, avoiding the necessity of accomplish the phase matching condition between the involved pump and probe signals, and reducing the power requirements compared to those of the traditional wavelength conversion implementations using four wave mixing (FWM). The proposed scheme also achieves symmetric conversion efficiency for up- and down-conversion. As a proof-of-concept, wavelength conversion of a train of 10 GHz chirped Gaussian-like pulses and their conjugated is experimentally demonstrated. PMID- 26368253 TI - High-power dual-fed traveling wave photodetector circuits in silicon photonics. AB - We introduce the concept of dual-illuminated photodetectors for high-power applications. Illuminating the photodetector on both sides doubles the number of optical channels, boosting DC and RF power handling capability. This concept is demonstrated utilizing multiple-stage dual-illuminated traveling wave photodetector circuits in silicon photonics, showing a maximum DC photocurrent of 112 mA and a 3-dB bandwidth of 40 GHz at 0.3 mA. Peak continuous-wave RF power is generated up to 12.3 dBm at 2 GHz and 5.3 dBm at 40 GHz, at a DC photocurrent of 55 mA. High speed broadband data signals are detected with eye amplitudes of 2.2 V and 1.3 V at 10 Gb/s and 40 Gb/s, respectively. A theoretical analysis is presented illustrating design tradeoffs for the multiple-stage photodetector circuits based on the bandwidth and power requirements. PMID- 26368254 TI - Temporal averaging of atmospheric turbulence-induced optical scintillation. AB - Based on the Rytov approximation we have developed for weak scintillation conditions a general expression for the temporal averaged variance of irradiance. The present analysis provides, for what we believe is the first time, a firm theoretical basis for the often-observed reduction of irradiance fluctuations of an optical beam due to atmospheric turbulence. Accurate elementary analytic approximations are presented here for plane, spherical and beam waves for predicting the averaging times required to obtain an arbitrary value of the ratio of the standard deviation to the mean of an optical beam propagating through an arbitrary path in the atmosphere. In particular, a novel application of differential absorption measurement for the purpose of measuring column integrated concentrations of various so-called greenhouse gas (GHG) atmospheric components is considered where the results of our analysis indicates that relatively short averaging times, on the order of a few seconds, are required to reduce the irradiance fluctuations to a value precise enough for GHG measurements of value to climate related studies. PMID- 26368255 TI - Aluminum based structures for manipulating short visible wavelength in-plane surface plasmon polariton propagation. AB - We report aluminum based structures for manipulation of surface plasmon polariton (SPP) propagation at short wavelength range. Our simulation shows that aluminum is a good metal to excite and propagate SPPs with blue light and that the SPP wavelength can be reduced from about 465 nm to about 265 nm by monitoring the thickness of a coated Si(3)N(4) layer above the aluminum film. It is also shown that the damping becomes more significant with the increase of the thickness of the Si(3)N(4) layer. We also experimentally demonstrated the SPP wavelength tuning effect for 20nm Si(3)N(4) layer covered Al, which can be explained by the variation of effective permittivity. The proposed Metal-Insulator-Air (MIA) structures with SPP wavelength tuning ability have potential applications in 2D optics. PMID- 26368256 TI - Curved optical tubes in a 4Pi focusing system. AB - We demonstrate the possibility of creating curved optical tubes in a 4Pi focusing system. The focal fields of such optical tubes have interesting properties: the energy is concentered in the neighborhood of a prescribed three-dimensional (3D) curve while the cross section is of hollow shape. The creation of these optical tubes is based on the annular focal spot of a vortex beam, which is employed as a building block. An optical tube is thus obtained by covering the central-axis curve of the tube by various such building blocks. Each building block has a certain orientation and position, realized by a rotation plus a certain translation. The spatial spectrum (the input field as well) of the optical tube is obtained by linearly superposing the spectrum of each transformed building block. The curve is rather arbitrary. Three examples of optical tubes: a torus, a solenoid and a trefoil knot are given, showing a good agreement with the expected results. PMID- 26368257 TI - Characterization and analysis of timing jitter in normal-dispersion mode-locked Er-fiber lasers with intra-cavity filtering. AB - We characterize and analyze the timing jitter of normal-dispersion mode-locked Er fiber lasers with intra-cavity filtering. The timing jitter of Er-fiber lasers with 9-nm bandpass filters operating at + 0.0084 ps(2) is measured to be 3.46 fs (rms) when integrated from 10 kHz to 10 MHz offset frequency, which is similar to the jitter level of typical stretched-pulse or soliton Er-fiber lasers. The numerical simulation based on split-step Fourier transform method shows that the measured high-frequency jitter is quantum noise-limited performance. We also develop an analytical model for filtered normal-dispersion fiber lasers by modifying the well-established noise model of stretched-pulse fiber lasers. The analytical modeling reveals that the jitter performance is improved mostly by reducing the chirp parameter by intra-cavity filtering. Both numerical simulation and analytical model fit fairly well with the measured timing jitter result. PMID- 26368258 TI - Towards quantitative atmospheric water vapor profiling with differential absorption lidar. AB - Differential Absorption Lidar (DIAL) is a powerful laser-based technique for trace gas profiling of the atmosphere. However, this technique is still under active development requiring precise and accurate wavelength stabilization, as well as accurate spectroscopic parameters of the specific resonance line and the effective absorption cross-section of the system. In this paper we describe a novel master laser system that extends our previous work for robust stabilization to virtually any number of multiple side-line laser wavelengths for the future probing to greater altitudes. In this paper, we also highlight the significance of laser spectral purity on DIAL accuracy, and illustrate a simple re-arrangement of a system for measuring effective absorption cross-section. We present a calibration technique where the laser light is guided to an absorption cell with 33 m path length, and a quantitative number density measurement is then used to obtain the effective absorption cross-section. The same absorption cell is then used for on-line laser stabilization, while microwave beat-frequencies are used to stabilize any number of off-line lasers. We present preliminary results using ~300 nJ, 1 MUs pulses at 3 kHz, with the seed laser operating as a nanojoule transmitter at 822.922 nm, and a receiver consisting of a photomultiplier tube (PMT) coupled to a 356 mm mirror. PMID- 26368259 TI - Electrically controllable multicolor cholesteric laser. AB - A new strategy to obtain multicolor lasing from cholesteric liquid crystals is presented. A four layer cell is prepared with three different cholesteric layers and a layer containing a photoluminescent dye. The three cholesteric mixtures are prepared so that their photonic band gaps are partially overlapped. Through this combination, two laser lines are obtained in the same spot under the pumping beam irradiation. Eventually, one of the laser lines can be switched off if an electric field is applied to the first or the last cholesteric layer. PMID- 26368260 TI - Measurement of optical thickness variation of BK7 plate by wavelength tuning interferometry. AB - This paper presents the derivation of a 17-sample phase-shifting algorithm that can compensate the miscalibration and first-order nonlinearity of phase shift error, coupling error, and bias modulation of the intensity and satisfy the fringe contrast maximum condition. The phase error of measurements performed using the 17-sample algorithm is discussed and compared with those of measurements obtained using other algorithms. Finally, the optical thickness variation of a BK7 optically transparent plate obtained using a wavelength tuning Fizeau interferometer and the 17-sample algorithm are presented. The experimental results indicate that the optical thickness variation measurement accuracy for the BK7 plate was 3 nm. PMID- 26368261 TI - Analysis of grating doublets for achromatic beam-splitting. AB - Achromatic beam-splitting grating doublets are designed for both continuous phase and binary phase gratings. By analyzing the sensitivity to lateral shifts between the two grating layers, it is shown that continuous-profile grating doublets are extremely difficult to fabricate. Achromatic grating doublets that have profiles with a constant first spatial derivative are significantly more resistant to lateral shifts between grating layers, where one design case showed a 17 times improvement in performance. Therefore, binary phase, multi-level phase, and blazed grating doublets perform significantly better than continuous phase grating doublets in the presence of a lateral shift between two grating layers. By studying the sensitivity to fabrication errors in the height of both grating layers, one grating layer height can be adjusted to maintain excellent performance over a large wavelength range if the other grating layer is fabricated incorrectly. It is shown in one design case that the performance of an achromatic Dammann grating doublet can be improved by a factor of 215 if the heights of the grating layers are chosen to minimize the performance change in the presence of fabrication errors. PMID- 26368262 TI - High resolution Fourier domain optical coherence tomography in the 2 MUm wavelength range using a broadband supercontinuum source: erratum. AB - We correct a mistake in the OCT system sensitivity given in our recent paper [Opt. Express23(3), 1992 (2015)]. PMID- 26368263 TI - Photonic coherence effects from dual-waveguide coupled pair of co-resonant microring resonators: erratum. AB - This erratum reports a correction of a typographical error in the theoretical study of coupled optical microring resonators [Opt. Express23, 12573-12587 (2015)]. The results and conclusions of the published work remain valid. PMID- 26368264 TI - Heptadecanoylcarnitine (C17) a novel candidate biomarker for newborn screening of propionic and methylmalonic acidemias. AB - BACKGROUND: 3-Hydroxypalmitoleoyl-carnitine (C16:1-OH) has recently been reported to be elevated in acylcarnitine profiles of patients with propionic acidemia (PA) or methylmalonic acidemia (MMA) during expanded newborn screening (NBS). High levels of C16:1-OH, combined with other hydroxylated long chain acylcarnitines are related to long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) and trifunctional protein (TFP) deficiency. METHODS: The acylcarnitine profile of two LCHADD patients was evaluated using liquid chromatography-tandem mass spectrometric method. A specific retention time was determined for each hydroxylated long chain acylcarnitine. The same method was applied to some neonatal dried blood spots (DBSs) from PA and MMA patients presenting abnormal C16:1-OH concentrations. RESULTS: The retention time of the peak corresponding to C16:1-OH in LCHADD patients differed from those in MMA and PA patients. Heptadecanoylcarnitine (C17) has been identified as the novel biomarker specific for PA and MMA patients through high resolution mass spectrometry (Orbitrap) experiments. We found that 21 out of 23 neonates (22 MMA, and 1PA) diagnosed through the Tuscany region NBS program exhibited significantly higher levels of C17 compared to controls. Twenty-three maternal deficiency (21 vitamin B12 deficiency, 1 homocystinuria and 1 gastrin deficiency) samples and 82 false positive for elevated propionylcarnitine (C3) were also analyzed. CONCLUSIONS: We have characterized a novel biomarker able to detect propionate disorders during expanded newborn screening (NBS). The use of this new biomarker may improve the analytical performances of NBS programs especially in laboratories where second tier tests are not performed. PMID- 26368265 TI - Changes in plasma thrombospondin-1 concentrations following acute intracerebral hemorrhage. AB - BACKGROUND: Angiogenesis is a fundamental process for brain development and repair. Thrombospondin-1 is the first identified endogenous angiogenesis inhibitor. Its expression in rat brain is upregulated after intracerebral hemorrhage (ICH). We determined whether plasma thrombospondin-1 concentrations are associated with injury severity and prognosis in ICH patients. METHODS: This observational, prospective study recruited 110 patients and 110 age- and gender matched healthy controls. Blood samples were collected from the patients at admission and from the healthy controls at study entry to measure plasma thrombospondin-1 concentrations. The endpoints included 1-week mortality, 6-month mortality, 6-month overall survival and 6-month unfavorable outcome (modified Rankin Scale score >2). RESULTS: Plasma thrombospondin-1 concentrations were markedly higher in patients than in healthy controls. Thrombospondin-1 was an independent predictive factor for all endpoints and plasma thrombospondin-1 concentrations were highly associated with injury severity reflected by hematoma volume and National Institutes of Health Stroke Scale score. Under receiver operating characteristic curves, plasma thrombospondin-1 concentrations had similar predictive values compared with hematoma volume and National Institutes of Health Stroke Scale score. CONCLUSIONS: Increased plasma thrombospondin-1 concentrations following ICH are independently associated with injury severity and short-term and long-term clinical outcomes. PMID- 26368266 TI - MicroRNAs: New players in intervertebral disc degeneration. AB - Chronic low back pain is generally attributed to intervertebral disc (IVD) degeneration (IDD), which is closely associated with apoptosis, extracellular matrix (ECM) disruption, cell proliferation and inflammatory response. Currently, there is no clinical therapy targeting the pathophysiology of disc degeneration. microRNAs (miRNAs) are a class of small noncoding RNA molecules that negatively regulate gene expression at the post-transcriptional levels. miRNAs not only regulate many normal physiological processes, but also play an important role in the development of most disorders, including degenerative disc disease. A variety of miRNAs are differentially expressed in degenerative human IVD tissues and cells. Among these, some of the miRNAs have been shown to be involved in multiple pathological processes during disc degeneration, including apoptosis, ECM degradation, cell proliferation and inflammatory response. This review will mainly focus on the expression profiles, roles, and therapeutic implications of miRNAs in IDD. With continued efforts, restoration of dysregulated miRNA expression may represent a promising biological treatment approach for mitigating or reversing IVD degeneration. PMID- 26368267 TI - Renal posttransplantation diabetes mellitus: An overview. AB - We conducted a literature review about renal posttransplantation diabetes mellitus (PTDM), a glucose metabolism alteration with high incidence. Immunosuppressive therapy, by different diabetogenic mechanisms, is the major risk factor for PTDM. Although corticosteroids and calcineurin inhibitors are the drugs most related to PTDM, the mechanisms of other drugs have been also investigated. Available data in the literature show that, in renal transplant patients, the oral glucose tolerance test presents the highest diagnostic sensitivity for PTDM, although fasting plasma glucose is the most requested test. In addition, we also discussed the possible role of hemoglobin A1C in the diagnosis of PTDM. Renal PTDM is associated with patient survival reduction, increased cardiovascular mortality and has been linked to worsening graft function. As crucial as the screening, the accurate management of the disease can ameliorate graft and patient survival as well as the quality of life of this especial population. Several drugs have been studied in PTDM patients in order to achieve a better glycemic control and, in the best scenario, prevent PTDM. We present proper management approaches that should help to reduce the possible long term consequences of PTDM. PMID- 26368268 TI - Kirschner wire is more effective than the nerve root retractor in treating patients with disc herniation. AB - OBJECTIVE: To investigate the value of using Kirschner wire in the intraspinal procedures. METHODS: From May 2011 to October 2013, a total of 46 patients with a single-level lumbar disc herniation with concomitant lumbar instability were randomly assigned to two groups at the time of admission. Group 1 had 23 patients who underwent posterior lumbar fusion using a nerve root retractor to drag nerve root, and Group 2 also had 23 patients who underwent the same operation by fixing Kirschner wires in the vertebral body to drag nerve root. All of these patients were assessed with visual analog scales (VAS) and Japanese Orthopaedic Association (JOA) scores before surgery, and were followed up at the time points of one week (VAS score only), three, six, and twelve months respectively after surgery. The actual retraction time of the nerve root of each patient was also recorded during the operation. RESULTS: The differences in VAS and JOA scores were not significant between Group 1 and 2 before surgery. However, these scores showed significant improvement in Group 2 at one week and three months after surgery compared with those in Group 1. At six and twelve month follow-up time points, no significant difference was observed between these two groups. However, the retraction time of the nerve root of the patients in Group 2 was significantly shorter than in Group 1. CONCLUSIONS: Using Kirschner wires instead of the nerve root retractor to pull nerve root in the patients with a single level lumbar disc herniation accompanied by the lumbar instability is more effective in reducing the dragging damage of the nerve root at early phases after surgery and in shortening retraction time. PMID- 26368269 TI - Effect of free radical scavenger, edaravone, for patients with carbon monoxide poisoning. AB - OBJECTIVE: Chronic neurological symptoms after carbon monoxide (CO) poisoning are caused by various biological processes in the damaged brain, with free radicals playing roles as mediators in establishing pathological processes leading to chronic neurological symptoms under CO poisoning. This study aimed to clarify the effects of a free radical scavenger, edaravone, in patients with CO poisoning. METHODS: We retrospectively compared two groups comprising patients treated with hyperbaric oxygenation alone (Group A, n=25) or edaravone in addition to hyperbaric oxygenation (Group B, n=25). Edaravone was administrated intravenously at 30 mg every 12h for 7 days. Patient characteristics, general conditions on admission, and frequency of chronic neurological symptoms were compared between groups. Among patients showing chronic neurological symptoms, cognitive function and daily activity were also compared between groups. RESULTS: No significant differences in characteristics or general conditions on admission were identified between groups. In Group B, no patients presented with marked complications caused by edaravone. Although chronic persisting symptoms were less frequent in Group B (n=1, 0.04%) than in Group A (n=5, 20%), this difference was not significant. In the 11 patients showing chronic symptoms, scores for cognitive function and daily activity in the chronic phase were better in Group B than in Group A, but no significant differences were apparent. CONCLUSIONS: The present results suggest that edaravone represents a tolerable and feasible treatment for CO-poisoned patients. Further studies are needed to clarify whether edaravone can favorably influence chronic neurological symptoms caused by CO poisoning. PMID- 26368270 TI - Effect of Antiretroviral Therapy on HIV-mediated Impairment of the Neutrophil Antimycobacterial Response. AB - RATIONALE: Experimental and epidemiological evidence suggests that neutrophils are important in the host response to tuberculosis. HIV infection, which increases the risk of tuberculosis, adversely affects neutrophil function. OBJECTIVES: To determine the impact of HIV and antiretroviral therapy on neutrophil antimycobacterial activity. METHODS: We performed a cross-sectional comparison of neutrophil functions in 20 antiretroviral-naive HIV-infected and 20 HIV-uninfected individuals using luminescence-, flow cytometry-, and ELISA-based assays. We then conducted a prospective study in the HIV-infected individuals investigating these parameters during the first 6 months of antiretroviral therapy. Surface markers of neutrophil activation were investigated in a separate cohort using flow cytometry. MEASUREMENTS AND MAIN RESULTS: HIV infection impaired control of Mycobacterium tuberculosis by neutrophils (mean ratio of mycobacterial luminescence in neutrophil samples vs. serum controls at 1 hour in HIV-infected participants, 0.88 +/- 0.13 vs. HIV-uninfected participants, 0.76 +/ 0.14; P = 0.01; at 24 hours, 0.82 +/- 0.13 vs. 0.71 +/- 0.13; P = 0.01). The extent of impairment correlated with log[HIV viral load]. Neutrophil cell death after 24 hours' incubation with M. tuberculosis was higher in the HIV-infected cohort (85.3 +/- 11.8% vs. 57.9 +/- 22.4% necrotic cells; P < 0.0001). Neutrophils from HIV-infected participants demonstrated significantly more CD62L negative cells (median, 23.0 vs. 8.5%; P = 0.008) and CD16-negative cells (3.2 vs. 1.3%, P = 0.03). Antiretroviral therapy restored mycobacterial restriction and pattern of neutrophil death toward levels seen in HIV-uninfected persons. CONCLUSIONS: Neutrophils in antiretroviral-naive HIV-infected persons are hyperactivated, eliminate M. tuberculosis less effectively than in HIV-uninfected individuals, and progress rapidly to necrotic cell death. These factors are ameliorated by antiretroviral therapy. PMID- 26368272 TI - The facile fabrication of few-layer graphene and graphite nanosheets by high pressure homogenization. AB - We demonstrated a facile and efficient approach for the fabrication of few-layer graphene in DMF and graphite nanosheets in water with the assistance of high pressure homogenization. This work provides a physical perspective for understanding the exfoliation of other layered materials in liquid phase exfoliation. PMID- 26368273 TI - The influence of L-opsin gene polymorphisms and neural ageing on spatio-chromatic contrast sensitivity in 20-71 year olds. AB - Chromatic contrast sensitivity may be a more sensitive measure of an individual's visual function than achromatic contrast sensitivity. Here, the first aim was to quantify individual- and age-related variations in chromatic contrast sensitivity to a range of spatial frequencies for stimuli along two complementary directions in color space. The second aim was to examine whether polymorphisms at specific amino acid residues of the L- and M-opsin genes (OPN1LW and OPN1MW) known to affect spectral tuning of the photoreceptors could influence spatio-chromatic contrast sensitivity. Chromatic contrast sensitivity functions were measured in 50 healthy individuals (20-71 years) employing a novel pseudo-isochromatic grating stimulus. The spatio-chromatic contrast sensitivity functions were found to be low pass for all subjects, independent of age and color vision. The results revealed a senescent decline in spatio-chromatic contrast sensitivity. There were considerable between-individual differences in sensitivity within each age decade for individuals 49 years old or younger, and age did not predict sensitivity for these age decades alone. Forty-six subjects (including a color deficient male and eight female carriers) were genotyped for L- and M-opsin genes. The Ser180Ala polymorphisms on the L-opsin gene were found to influence the subject's color discrimination and their sensitivity to spatio-chromatic patterns. The results expose the significant role of neural and genetic factors in the deterioration of visual function with increasing age. PMID- 26368274 TI - Door to disposition times for obstetric triage visits: Is there a July phenomenon? AB - The July phenomenon refers to a change in patient outcomes within teaching hospitals with the arrival of new and inexperienced house staff at the start of the academic year (July to June). In our obstetric triage unit we retrospectively evaluated the door to disposition time (DTDT) for 1817 patients who presented across July, December and May of academic years 2009-2010 and 2010-2011. DTDT was examined for three visit levels: non-urgent, urgent and emergent. No significant differences in disposition time were found for emergent visits. For urgent visits the median DTDT significantly decreased from 171 min in July to 155 min in December and 135 min in May (p < 0.001). Similarly for non-urgent visits, the median DTDT was greater during July than May (179 min vs. 133 min; p < 0.05). Electronic medical records (EMRs) were implemented in November 2010. Following the introduction of EMR shorter DTDT was seen in December 2010 versus December 2009 (median, 171 min vs. 150 min; p < 0.05), respectively. Our findings suggest a 'July Phenomenon' of greater disposition intervals for urgent and non-urgent obstetric triage visits across the academic year. Additionally the use of EMRs may facilitate patient flow through the OB triage unit. PMID- 26368271 TI - Portion, package or tableware size for changing selection and consumption of food, alcohol and tobacco. AB - BACKGROUND: Overeating and harmful alcohol and tobacco use have been linked to the aetiology of various non-communicable diseases, which are among the leading global causes of morbidity and premature mortality. As people are repeatedly exposed to varying sizes and shapes of food, alcohol and tobacco products in environments such as shops, restaurants, bars and homes, this has stimulated public health policy interest in product size and shape as potential targets for intervention. OBJECTIVES: 1) To assess the effects of interventions involving exposure to different sizes or sets of physical dimensions of a portion, package, individual unit or item of tableware on unregulated selection or consumption of food, alcohol or tobacco products in adults and children.2) To assess the extent to which these effects may be modified by study, intervention and participant characteristics. SEARCH METHODS: We searched CENTRAL, MEDLINE, EMBASE, PsycINFO, eight other published or grey literature databases, trial registries and key websites up to November 2012, followed by citation searches and contacts with study authors. This original search identified eligible studies published up to July 2013, which are fully incorporated into the review. We conducted an updated search up to 30 January 2015 but further eligible studies are not yet fully incorporated due to their minimal potential to change the conclusions. SELECTION CRITERIA: Randomised controlled trials with between-subjects (parallel-group) or within-subjects (cross-over) designs, conducted in laboratory or field settings, in adults or children. Eligible studies compared at least two groups of participants, each exposed to a different size or shape of a portion of a food (including non-alcoholic beverages), alcohol or tobacco product, its package or individual unit size, or of an item of tableware used to consume it, and included a measure of unregulated selection or consumption of food, alcohol or tobacco. DATA COLLECTION AND ANALYSIS: We applied standard Cochrane methods to select eligible studies for inclusion and to collect data and assess risk of bias. We calculated study-level effect sizes as standardised mean differences (SMDs) between comparison groups, measured as quantities selected or consumed. We combined these results using random-effects meta-analysis models to estimate summary effect sizes (SMDs with 95% confidence intervals (CIs)) for each outcome for size and shape comparisons. We rated the overall quality of evidence using the GRADE system. Finally, we used meta-regression analysis to investigate statistical associations between summary effect sizes and variant study, intervention or participant characteristics. MAIN RESULTS: The current version of this review includes 72 studies, published between 1978 and July 2013, assessed as being at overall unclear or high risk of bias with respect to selection and consumption outcomes. Ninety-six per cent of included studies (69/72) manipulated food products and 4% (3/72) manipulated cigarettes. No included studies manipulated alcohol products. Forty-nine per cent (35/72) manipulated portion size, 14% (10/72) package size and 21% (15/72) tableware size or shape. More studies investigated effects among adults (76% (55/72)) than children and all studies were conducted in high-income countries - predominantly in the USA (81% (58/72)). Sources of funding were reported for the majority of studies, with no evidence of funding by agencies with possible commercial interests in their results.A meta-analysis of 86 independent comparisons from 58 studies (6603 participants) found a small to moderate effect of portion, package, individual unit or tableware size on consumption of food (SMD 0.38, 95% CI 0.29 to 0.46), providing moderate quality evidence that exposure to larger sizes increased quantities of food consumed among children (SMD 0.21, 95% CI 0.10 to 0.31) and adults (SMD 0.46, 95% CI 0.40 to 0.52). The size of this effect suggests that, if sustained reductions in exposure to larger-sized food portions, packages and tableware could be achieved across the whole diet, this could reduce average daily energy consumed from food by between 144 and 228 kcal (8.5% to 13.5% from a baseline of 1689 kcal) among UK children and adults. A meta-analysis of six independent comparisons from three studies (108 participants) found low quality evidence for no difference in the effect of cigarette length on consumption (SMD 0.25, 95% CI -0.14 to 0.65).One included study (50 participants) estimated a large effect on consumption of exposure to differently shaped tableware (SMD 1.17, 95% CI 0.57 to 1.78), rated as very low quality evidence that exposure to shorter, wider bottles (versus taller, narrower bottles) increased quantities of water consumed by young adult participants.A meta-analysis of 13 independent comparisons from 10 studies (1164 participants) found a small to moderate effect of portion or tableware size on selection of food (SMD 0.42, 95% CI 0.24 to 0.59), rated as moderate quality evidence that exposure to larger sizes increased the quantities of food people selected for subsequent consumption. This effect was present among adults (SMD 0.55, 95% CI 0.35 to 0.75) but not children (SMD 0.14, 95% CI -0.06 to 0.34).In addition, a meta-analysis of three independent comparisons from three studies (232 participants) found a very large effect of exposure to differently shaped tableware on selection of non-alcoholic beverages (SMD 1.47, 95% CI 0.52 to 2.43), rated as low quality evidence that exposure to shorter, wider (versus taller, narrower) glasses or bottles increased the quantities selected for subsequent consumption among adults (SMD 2.31, 95% CI 1.79 to 2.83) and children (SMD 1.03, 95% CI 0.41 to 1.65). AUTHORS' CONCLUSIONS: This review found that people consistently consume more food and drink when offered larger-sized portions, packages or tableware than when offered smaller sized versions. This suggests that policies and practices that successfully reduce the size, availability and appeal of larger-sized portions, packages, individual units and tableware can contribute to meaningful reductions in the quantities of food (including non-alcoholic beverages) people select and consume in the immediate and short term. However, it is uncertain whether reducing portions at the smaller end of the size range can be as effective in reducing food consumption as reductions at the larger end of the range. We are unable to highlight clear implications for tobacco or alcohol policy due to identified gaps in the current evidence base. PMID- 26368277 TI - Design of a compact antenna with flared groundplane for a wearable breast hyperthermia system. AB - PURPOSE: Currently available microwave hyperthermia systems for breast cancer treatment do not conform to the intact breast and provide limited control of heating patterns, thereby hindering an effective treatment. A compact patch antenna with a flared groundplane that may be integrated within a wearable hyperthermia system for the treatment of the intact breast disease is proposed. MATERIALS AND METHODS: A 3D simulation-based approach was employed to optimise the antenna design with the objective of maximising the hyperthermia treatment volume (41 degrees C iso-therm) while maintaining good impedance matching. The optimised antenna design was fabricated and experimentally evaluated with ex vivo tissue measurements. RESULTS: The optimised compact antenna yielded a -10 dB bandwidth of 90 MHz centred at 915 MHz, and was capable of creating hyperthermia treatment volumes up to 14.4 cm(3) (31 mm * 28 mm * 32 mm) with an input power of 15 W. Experimentally measured reflection coefficient and transient temperature profiles were in good agreement with simulated profiles. Variations of + 50% in blood perfusion yielded variations in the treatment volume up to 11.5%. When compared to an antenna with a similar patch element employing a conventional rectangular groundplane, the antenna with flared groundplane afforded 22.3% reduction in required power levels to reach the same temperature, and yielded 2.4 times larger treatment volumes. CONCLUSION: The proposed patch antenna with a flared groundplane may be integrated within a wearable applicator for hyperthermia treatment of intact breast targets and has the potential to improve efficiency, increase patient comfort, and ultimately clinical outcomes. PMID- 26368276 TI - Bow Your Head in Shame, or, Hold Your Head Up with Pride: Semantic Processing of Self-Esteem Concepts Orients Attention Vertically. AB - Embodied cognition holds that abstract concepts are grounded in perceptual-motor simulations. If a given embodied metaphor maps onto a spatial representation, then thinking of that concept should bias the allocation of attention. In this study, we used positive and negative self-esteem words to examine two properties of conceptual cueing. First, we tested the orientation-specificity hypothesis, which predicts that conceptual cues should selectively activate certain spatial axes (in this case, valenced self-esteem concepts should activate vertical space), instead of any spatial continuum. Second, we tested whether conceptual cueing requires semantic processing, or if it can be achieved with shallow visual processing of the cue words. Participants viewed centrally presented words consisting of high or low self-esteem traits (e.g., brave, timid) before detecting a target above or below the cue in the vertical condition, or on the left or right of the word in the horizontal condition. Participants were faster to detect targets when their location was compatible with the valence of the word cues, but only in the vertical condition. Moreover, this effect was observed when participants processed the semantics of the word, but not when processing its orthography. The results show that conceptual cueing by spatial metaphors is orientation-specific, and that an explicit consideration of the word cues' semantics is required for conceptual cueing to occur. PMID- 26368278 TI - Characterizing Behavioral and Brain Changes Associated with Practicing Reasoning Skills. AB - We have reported previously that intensive preparation for a standardized test that taxes reasoning leads to changes in structural and functional connectivity within the frontoparietal network. Here, we investigated whether reasoning instruction transfers to improvement on unpracticed tests of reasoning, and whether these improvements are associated with changes in neural recruitment during reasoning task performance. We found behavioral evidence for transfer to a transitive inference task, but no evidence for transfer to a rule generation task. Across both tasks, we observed reduced lateral prefrontal activation in the trained group relative to the control group, consistent with other studies of practice-related changes in brain activation. In the transitive inference task, we observed enhanced suppression of task-negative, or default-mode, regions, consistent with work suggesting that better cognitive skills are associated with more efficient switching between networks. In the rule generation task, we found a pattern consistent with a training-related shift in the balance between phonological and visuospatial processing. Broadly, we discuss general methodological considerations related to the analysis and interpretation of training-related changes in brain activation. In summary, we present preliminary evidence for changes in brain activation associated with practice of high-level cognitive skills. PMID- 26368279 TI - Emergence of Amoxicillin-Resistant Variants of Spain9V-ST156 Pneumococci Expressing Serotype 11A Correlates with Their Ability to Evade the Host Immune Response. AB - Capsular switching allows pre-existing clones of Streptococcus pneumoniae expressing vaccine serotypes to escape the vaccine-induced immunity by acquisition of capsular genes from pneumococci of a non-vaccine serotype. Here, we have analysed the clonal composition of 492 clinical isolates of serotype 11A causing invasive disease in Spain (2000-2012), and their ability to evade the host immune response. Antibiograms, serotyping and molecular typing were performed. The restriction profiles of pbp2x, pbp1a and pbp2b genes were also analysed. Interaction with the complement components C1q, C3b, C4BP, and factor H was explored whereas opsonophagocytosis assays were performed using a human cell line differentiated to neutrophils. Biofilm formation and the polymorphisms of the major autolysin LytA were evaluated. The main genotypes of the 11A pneumococci were: ST62 (447 isolates, 90.6%), followed by ST6521 (35 isolates, 7.3%) and ST838 (10 isolates, 2.1%). Beta lactam resistant serotype 11A variants of genotypes ST838 and ST6521 closely related to the Spain9V-ST156 clone were first detected in 2005. A different pattern of evasion of complement immunity and phagocytosis was observed between genotypes. The emergence of one vaccine escape variant of Spain9V-ST156 (ST652111A), showing a high potential to avoid the host immune response, was observed. In addition, isolates of ST652111A showed higher ability to produce biofilms than ST83811A or ST6211A, which may have contributed to the emergence of this PEN-resistant ST652111A genotype in the last few years. The emergence of penicillin-resistant 11A invasive variants of the highly successful ST156 clonal complex merits close monitoring. PMID- 26368280 TI - Prooxidant/Antioxidant Balance in Hypoxia: A Cross-Over Study on Normobaric vs. Hypobaric "Live High-Train Low". AB - "Live High-Train Low" (LHTL) training can alter oxidative status of athletes. This study compared prooxidant/antioxidant balance responses following two LHTL protocols of the same duration and at the same living altitude of 2250 m in either normobaric (NH) or hypobaric (HH) hypoxia. Twenty-four well-trained triathletes underwent the following two 18-day LHTL protocols in a cross-over and randomized manner: Living altitude (PIO2 = 111.9 +/- 0.6 vs. 111.6 +/- 0.6 mmHg in NH and HH, respectively); training "natural" altitude (~1000-1100 m) and training loads were precisely matched between both LHTL protocols. Plasma levels of oxidative stress [advanced oxidation protein products (AOPP) and nitrotyrosine] and antioxidant markers [ferric-reducing antioxidant power (FRAP), superoxide dismutase (SOD) and catalase], NO metabolism end-products (NOx) and uric acid (UA) were determined before (Pre) and after (Post) the LHTL. Cumulative hypoxic exposure was lower during the NH (229 +/- 6 hrs.) compared to the HH (310 +/- 4 hrs.; P<0.01) protocol. Following the LHTL, the concentration of AOPP decreased (-27%; P<0.01) and nitrotyrosine increased (+67%; P<0.05) in HH only. FRAP was decreased (-27%; P<0.05) after the NH while was SOD and UA were only increased following the HH (SOD: +54%; P<0.01 and UA: +15%; P<0.01). Catalase activity was increased in the NH only (+20%; P<0.05). These data suggest that 18 days of LHTL performed in either NH or HH differentially affect oxidative status of athletes. Higher oxidative stress levels following the HH LHTL might be explained by the higher overall hypoxic dose and different physiological responses between the NH and HH. PMID- 26368281 TI - Site-Selective Monitoring of the Interaction of the SRA Domain of UHRF1 with Target DNA Sequences Labeled with 2-Aminopurine. AB - UHRF1 plays a central role in the maintenance and transmission of epigenetic modifications by recruiting DNMT1 to hemimethylated CpG sites via its SET and RING-associated (SRA) domain, ensuring error-free duplication of methylation profiles. To characterize SRA-induced changes in the conformation and dynamics of a target 12 bp DNA duplex as a function of the methylation status, we labeled duplexes by the environment-sensitive probe 2-aminopurine (2-Ap) at various positions near or far from the central CpG recognition site containing either a nonmodified cytosine (NM duplex), a methylated cytosine (HM duplex), or methylated cytosines on both strands (BM duplex). Steady-state and time-resolved fluorescence indicated that binding of SRA induced modest conformational and dynamical changes in NM, HM, and BM duplexes, with only slight destabilization of base pairs, restriction of global duplex flexibility, and diminution of local nucleobase mobility. Moreover, significant restriction of the local motion of residues flanking the methylcytosine in the HM duplex suggested that these residues are more rigidly bound to SRA, in line with a slightly higher affinity of the HM duplex as compared to that of the NM or BM duplex. Our results are consistent with a "reader" role, in which the SRA domain scans DNA sequences for hemimethylated CpG sites without perturbation of the structure of contacted nucleotides. PMID- 26368282 TI - Correction: Rural-Urban Differences in Household Treatment-Seeking Behaviour for Suspected Malaria in Children at Bata District, Equatorial Guinea. PMID- 26368284 TI - Bottle gourd rootstock-grafting promotes photosynthesis by regulating the stomata and non-stomata performances in leaves of watermelon seedlings under NaCl stress. AB - Previously, we found that the amelioration of photosynthetic capacity by bottle gourd (Lagenaria siceraria Standl.) rootstock in watermelon seedlings (Citrullus lanatus [Thunb.] Mansf.) with salt treatment might be closely related to the enzymes in Calvin cycle such as ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) (Yang et al., 2012). We confirmed this and showed more details in this study that improved photosynthesis of watermelon plants by bottle gourd rootstock was associated with the decreased stomata resistance and the increased photochemical activity and photosynthetic metabolism with or without 100mM NaCl stress for 3 days. The analysis of gas exchange parameters showed that self grafted plants suffered serious non-stomatal limitation to photosynthesis under salt stress while rootstock-grafted plants were mainly affected by stomata limitation in stress conditions. Further, results showed that NaCl stress markedly reduced the chlorophyll content, damaged the structure of photosynthetic apparatus, and inhibited photochemical activity and CO2 assimilation in self grafted plants. In contrast, rootstock-grafting increased the chlorophyll content, especially chlorophyll b, and minimized the harmful effects on photosystem II (PSII) reaction center and the thylakoids structure induced by NaCl stress. Furthermore, rootstock-grafting enhanced the content and activity of Rubisco and thus elevated carbon fixation in the leaves of watermelon scions under salt stress. The gene expressions of enzymes related to ribulose-1,5 bisphosphate (RuBP) regeneration were also up-regulated by rootstock and this probably guaranteed the sufficient supply of RuBP for the operation of Calvin cycle in watermelon scions under salt stress. Thus, bottle gourd rootstock promoted photosynthesis by the activation of stomatal and non-stomatal abilities, especially the regulation of a variety of photosynthetic enzymes, including Rubisco in grafted watermelon plants under NaCl stress. PMID- 26368283 TI - Scanning MscL Channels with Targeted Post-Translational Modifications for Functional Alterations. AB - Mechanosensitive channels are present in all living organisms and are thought to underlie the senses of touch and hearing as well as various important physiological functions like osmoregulation and vasoregulation. The mechanosensitive channel of large conductance (MscL) from Escherichia coli was the first protein shown to encode mechanosensitive channel activity and serves as a paradigm for how a channel senses and responds to mechanical stimuli. MscL plays a role in osmoprotection in E. coli, acting as an emergency release valve that is activated by membrane tension due to cell swelling after an osmotic down shock. Using an osmotically fragile strain in an osmotic down-shock assay, channel functionality can be directly determined in vivo. In addition, using thiol reagents and expressed MscL proteins with a single cysteine substitution, we have shown that targeted post-translational modifications can be performed, and that any alterations that lead to dysfunctional proteins can be identified by this in vivo assay. Here, we present the results of such a scan performed on 113 MscL cysteine mutants using five different sulfhydryl-reacting probes to confer different charges or hydrophobicity to each site. We assessed which of these targeted modifications affected channel function and the top candidates were further studied using patch clamp to directly determine how channel activity was affected. This comprehensive screen has identified many residues that are critical for channel function as well as highlighted MscL domains and residues that undergo the most drastic environmental changes upon gating. PMID- 26368285 TI - Season-long increases in perceived muscle soreness in professional rugby league players: role of player position, match characteristics and playing surface. AB - Rugby League (RL) is a high-impact collision sport characterised by repeated sprints and numerous high-speed impacts and consequently players often report immediate and prolonged muscle soreness in the days after a match. We examined muscle soreness after matches during a full season to understand the extent to which match characteristics influence soreness. Thirty-one elite Super League players provided daily measures of muscle soreness after each of the 26 competitive fixtures of the 2012 season. Playing position, phase of the season, playing surface and match characteristics were recorded from each match. Muscle soreness peaked at day 1 and was still apparent at day 4 post-game with no attenuation in the magnitude of muscle soreness over the course of the season. Neither playing position, phase of season or playing surface had any effects on the extent of muscle soreness. Playing time and total number of collisions were significantly correlated with higher ratings of muscle soreness, especially in the forwards. These data indicate the absence "contact adaptations" in elite rugby players with soreness present throughout the entire season. Strategies must now be implemented to deal with the physical and psychological consequences of prolonged feeling of pain. PMID- 26368286 TI - Screening for Differentially Expressed Proteins Relevant to the Differential Diagnosis of Sarcoidosis and Tuberculosis. AB - BACKGROUND: In this study, we sought to identify differentially expressed proteins in the serum of patients with sarcoidosis or tuberculosis and to evaluate these proteins as markers for the differential diagnosis of sarcoidosis and sputum-negative tuberculosis. METHODS: Using protein microarrays, we identified 3 proteins exhibiting differential expression between patients with sarcoidosis and tuberculosis. Elevated expression of these proteins was verified using the enzyme-linked immunosorbent assay (ELISA) and was further confirmed by immunohistochemistry. Receiver operating characteristic (ROC) curve, logistic regression analysis, parallel, and serial tests were used to evaluate the diagnostic efficacy of the proteins. RESULTS: Intercellular Adhesion Molecule 1(ICAM-1) and leptin were screened for differentially expressed proteins relevant to sarcoidosis and tuberculosis. Using ROC curves, we found that ICAM-1 (cutoff value: 57740 pg/mL) had an area under the curve (AUC), sensitivity, and specificity of 0.718, 62.3%, and 79.5% respectively, while leptin (cutoff value: 1193.186 pg/mL) had an AUC, sensitivity, and specificity of 0.763, 88.3%, and 65.8%, respectively. Logistic regression analysis revealed that the AUC, sensitivity, and specificity of combined leptin and ICAM-1 were 0.787, 89.6%, and 65.8%, respectively, while those of combined leptin, ICAM-1, and body mass index (BMI) were 0.837, 90.9%, and 64.4%, respectively, which had the greatest diagnostic value. Parallel and serial tests indicated that the BMI-leptin parallel with the ICAM-1 serial was the best diagnostic method, achieving a sensitivity and specificity of 86.5% and 73.1%, respectively. Thus, our results identified elevated expression of ICAM-1 and leptin in serum and granulomas of sarcoidosis patients. CONCLUSIONS: ICAM-1 and leptin were found to be potential markers for the diagnosis of sarcoidosis and differential diagnosis of sarcoidosis and sputum-negative tuberculosis. PMID- 26368287 TI - A Point-of-Care Immunosensor for Human Chorionic Gonadotropin in Clinical Urine Samples Using a Cuneated Polysilicon Nanogap Lab-on-Chip. AB - Human chorionic gonadotropin (hCG), a glycoprotein hormone secreted from the placenta, is a key molecule that indicates pregnancy. Here, we have designed a cost-effective, label-free, in situ point-of-care (POC) immunosensor to estimate hCG using a cuneated 25 nm polysilicon nanogap electrode. A tiny chip with the dimensions of 20.5 * 12.5 mm was fabricated using conventional lithography and size expansion techniques. Furthermore, the sensing surface was functionalized by (3-aminopropyl)triethoxysilane and quantitatively measured the variations in hCG levels from clinically obtained human urine samples. The dielectric properties of the present sensor are shown with a capacitance above 40 nF for samples from pregnant women; it was lower with samples from non-pregnant women. Furthermore, it has been proven that our sensor has a wide linear range of detection, as a sensitivity of 835.88 MUA mIU(-1) ml(-2) cm(-2) was attained, and the detection limit was 0.28 mIU/ml (27.78 pg/ml). The dissociation constant Kd of the specific antigen binding to the anti-hCG was calculated as 2.23 +/- 0.66 mIU, and the maximum number of binding sites per antigen was Bmax = 22.54 +/- 1.46 mIU. The sensing system shown here, with a narrow nanogap, is suitable for high-throughput POC diagnosis, and a single injection can obtain triplicate data or parallel analyses of different targets. PMID- 26368288 TI - Growth Conditions and Cell Cycle Phase Modulate Phase Transition Temperatures in RBL-2H3 Derived Plasma Membrane Vesicles. AB - Giant plasma membrane vesicle (GPMV) isolated from a flask of RBL-2H3 cells appear uniform at physiological temperatures and contain coexisting liquid ordered and liquid-disordered phases at low temperatures. While a single GPMV transitions between these two states at a well-defined temperature, there is significant vesicle-to-vesicle heterogeneity in a single preparation of cells, and average transition temperatures can vary significantly between preparations. In this study, we explore how GPMV transition temperatures depend on growth conditions, and find that average transition temperatures are negatively correlated with average cell density over 15 degrees C in transition temperature and nearly three orders of magnitude in average surface density. In addition, average transition temperatures are reduced by close to 10 degrees C when GPMVs are isolated from cells starved of serum overnight, and elevated transition temperatures are restored when serum-starved cells are incubated in serum containing media for 12 h. We also investigated variation in transition temperature of GPMVs isolated from cells synchronized at the G1/S border through a double Thymidine block and find that average transition temperatures are systematically higher in GPMVs produced from G1 or M phase cells than in GPMVs prepared from S or G1 phase cells. Reduced miscibility transition temperatures are also observed in GPMVs prepared from cells treated with TRAIL to induce apoptosis or sphingomyelinase, and in some cases a gel phase is observed at temperatures above the miscibility transition in these vesicles. We conclude that at least some variability in GPMV transition temperature arises from variation in the local density of cells and asynchrony of the cell cycle. It is hypothesized that GPMV transition temperatures are a proxy for the magnitude of lipid-mediated membrane heterogeneity in intact cell plasma membranes at growth temperatures. If so, these results suggest that cells tune their plasma membrane composition in order to control the magnitude of membrane heterogeneity in response to different growth conditions. PMID- 26368290 TI - A computational strategy for predicting lineage specifiers in stem cell subpopulations. AB - Stem cell differentiation is a complex biological event. Our understanding of this process is partly hampered by the co-existence of different cell subpopulations within a given population, which are characterized by different gene expression states driven by different underlying transcriptional regulatory networks (TRNs). Such cellular heterogeneity has been recently explored with the modern single-cell gene expression profiling technologies, such as single-cell RT PCR and RNA-seq. However, the identification of cell subpopulation-specific TRNs and genes determining specific lineage commitment (i.e., lineage specifiers) remains a challenge due to the slower development of appropriate computational and experimental workflows. Here, we propose a computational method for predicting lineage specifiers for different cell subpopulations in binary-fate differentiation events. Our method first reconstructs subpopulation-specific TRNs, which is more realistic than reconstructing a single TRN representing multiple cell subpopulations. Then, it predicts lineage specifiers based on a model that assumes that each parental stem cell subpopulation is in a stable state maintained by its specific TRN stability core. In addition, this stable state is maintained in the parental cell subpopulation by the balanced gene expression pattern of pairs of opposing lineage specifiers for mutually exclusive different daughter cell subpopulations. To this end, we devised a statistical metric for identifying opposing lineage specifier pairs that show a significant ratio change upon differentiation. Application of this computational method to three different stem cell systems predicted known and putative novel lineage specifiers, which could be experimentally tested. Our method does not require pre selection of putative candidate genes, and can be applied to any binary-fate differentiation system for which single-cell gene expression data are available. Furthermore, this method is compatible with both single-cell RT-PCR and single cell RNA-seq data. Given the increasing importance of single-cell gene expression data in stem cell biology and regenerative medicine, approaches like ours would be useful for the identification of lineage specifiers and their associated TRN stability cores. PMID- 26368289 TI - Photoreceptor Specificity in the Light-Induced and COP1-Mediated Rapid Degradation of the Repressor of Photomorphogenesis SPA2 in Arabidopsis. AB - The Arabidopsis COP1/SPA E3 ubiquitin ligase is a key negative regulator that represses light signaling in darkness by targeting transcription factors involved in the light response for degradation. The COP1/SPA complex consists of COP1 and members of the four-member SPA protein family (SPA1-SPA4). Genetic analysis indicated that COP1/SPA2 function is particularly strongly repressed by light when compared to complexes carrying the other three SPAs, thereby promoting a light response after exposure of plants to extremely low light. Here, we show that the SPA2 protein is degraded within 5-15 min after exposure of dark-grown seedlings to a pulse of light. Phytochrome photoreceptors are required for the rapid degradation of SPA2 in red, far-red and also in blue light, whereas cryptochromes are not involved in the rapid, blue light-induced reduction in SPA2 protein levels. These results uncover a photoreceptor-specific mechanism of light induced inhibition of COP1/SPA2 function. Phytochrome A (phyA) is required for the severe blue light responsiveness of spa triple mutants expressing only SPA2, thus confirming the important role of phyA in downregulating SPA2 function in blue light. In blue light, SPA2 forms a complex with cryptochrome 1 (cry1), but not with cryptochrome 2 (cry2) in vivo, indicating that the lack of a rapid blue light response of the SPA2 protein is only in part caused by a failure to interact with cryptochromes. Since SPA1 interacts with both cry1 and cry2, these results provide first molecular evidence that the light-regulation of different SPA proteins diverged during evolution. SPA2 degradation in the light requires COP1 and the COP1-interacting coiled-coil domain of SPA2, supporting that SPA2 is ubiquitinated by COP1. We propose that light perceived by phytochromes causes a switch in the ubiquitination activity of COP1/SPA2 from ubiquitinating downstream substrates to ubiquitinating SPA2, which subsequently causes a repression of COP1/SPA2 function. PMID- 26368291 TI - Aqueous root extract of Lecaniodiscus cupanioides restores nitric oxide/cyclic guanosine monophosphate pathway in sexually impaired male rats. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Aqueous root extract of Lecaniodiscus cupanioides is widely used in the management of sexual dysfunction in Nigeria. The effect of aqueous root extract of L. cupanioides root on the concentrations of penile cyclic Guanosine Monophosphate (cGMP) and plasma nitric oxide in paroxetine induced sexually impaired male rats was evaluated. METHODS: Thirty (30) albino rats were assigned into six groups (A, B, C, D, E and F) of five rats each such that animals in Group A (control) received distilled water while those in Groups B, C, D, E and F which were induced into sexual dysfunction (p.o 10mg/kg of paroxetine hydrochloride suspension in Tween-80) and in addition received distilled water, 7.14 mg/kg body weight of a reference herbal drug (PowmaxM), 25, 50 and 100mg/kg body weight of the extract respectively, orally, once daily for five days. RESULTS: Administration of paroxetine significantly reduced the levels of penile cyclic Guanosine Monophosphate (cGMP) and plasma nitric oxide. These decreases were dose dependently reversed by the aqueous extract of L. cupanioides root. The reversal by the 25 and 50mg/kg body weight of the extract compared favorably with the PowmaxM, whereas the 100mg/kg body weight of the extract compared favorably with the non-sexually impaired distilled water treated control animals. CONCLUSION: The results of this study show that aqueous extract of L. cupanioides root restored the levels of cGMP and nitric oxide in sexually impaired rats. This study further lends credence to the use of aqueous root extract of L. cupanioides in the management of sexual dysfunction in Nigeria. PMID- 26368292 TI - Charge is an important determinant of hemodynamic and adverse cardiovascular effects of cationic drugs. AB - Cationic compounds are diverse and atypical therapeutic substances. In the present study we examined whether a prototypical class effect of cationic drugs in the cardiovascular system exists and whether this might be predictable on the basis of chemistry. The dose-dependent effects of cationic compounds of varying molecular weights and charge were examined on the blood pressure (BP), heart rate (HR) and the ECG in anesthetized rats. The compounds examined were protamine, hexadimethrine, tetraethylammonium (TEA), low molecular weight poly-L-lysine (LMW PLL) and high molecular weight PLL (HMW-PLL). All of the compounds examined except TEA produced a dose-dependent reduction in BP. No changes occurred in HR even when high doses were administered. The ECG effects of these cationic compounds included a dose-dependent prolongation of the QT interval, especially at higher doses. All compounds transiently decreased the size of the P-wave after i.v. bolus administration whereas only protamine and hexadimethrine prolonged the PR and QRS intervals and only at the highest dose (32 mg/kg) administered. All cationic compounds, except TEA and saline, evoked ventricular premature beats (VPB), and protamine and HMW-PLL also evoked brief episodes of ventricular tachycardia (VT). The incidence and frequency of arrhythmias was not dose dependent and no animals experienced protracted episodes of arrhythmia incidence. These dose dependent effects of the polycationic compounds tested suggest a collective mechanism of action that relates the effect of charge of the compound to the onset and persistence of observed cardiovascular toxicity, and adverse cardiovascular effect risk appears to be predictable on this basis. PMID- 26368293 TI - 21st-Century Healthcare Policy and the Regulation of Laboratory-Developed Tests. PMID- 26368295 TI - Methadone Recycling Sustains Drug Reservoir in Tissue. AB - We hypothesize that there is a tissue store of methadone content in humans that is not directly accessible, but is quantifiable. Further, we hypothesize the mechanism by which methadone content is sustained in tissue stores involves methadone uptake, storage, and release from tissue depots in the body (recycling). Accordingly, we hypothesize that such tissue stores, in part, determine plasma methadone levels. We studied a random sample of six opioid-naive healthy subjects. We performed a clinical trial simulation in silico using pharmacokinetic modeling. We found a large tissue store of methadone content whose size was much larger than methadone's size in plasma in response to a single oral dose of methadone 10 mg. The tissue store measured 13-17 mg. This finding could only be explained by the contemporaneous storage of methadone in tissue with dose recycling. We found that methadone recycles 2-5 times through an inaccessible extravascular compartment (IAC), from an accessible plasma containing compartment (AC), before exiting irreversibly. We estimate the rate of accumulation (or storage) of methadone in tissue was 0.029-7.29 mg/h. We predict 39 +/- 13% to 83 +/- 6% of methadone's tissue stores "spillover" into the circulation. Our results indicate that there exists a large quantifiable tissue store of methadone in humans. Our results support the notion that methadone in humans undergoes tissue uptake, storage, release into the circulation, reuptake from the circulation, and re-release into the circulation, and that spillover of methadone from tissue stores, in part, maintain plasma methadone levels in humans. PMID- 26368294 TI - Prevalence of Anal Human Papillomavirus Infection and Risk Factors among HIV positive Patients in Tokyo, Japan. AB - BACKGROUND: Oncogenic human papillomavirus (HPV) infection, particularly multiple HPV types, is recognized as a necessary cause of anal cancer. However, a limited number of studies have reported the prevalence of anal HPV infection in Asia. We determined the prevalence, genotypes, and risk factors for anal HPV infection in Japanese HIV-positive men who have sex with men (MSM), heterosexual men, and women. METHODS: This cross-sectional study included 421 HIV-positive patients. At enrollment, we collected data on smoking, alcohol, co-morbidities, drugs, CD4 cell counts, HIV RNA levels, highly active anti-retroviral therapy (HAART) duration, sexually transmitted infections (STIs), and serological screening (syphilis, hepatitis B virus, Chlamydia trachomatis, Entamoeba histolytica). Anal swabs were collected for oncogenic HPV genotyping. RESULTS: Oncogenic HPV rate was 75.9% in MSM, 20.6% in heterosexual men, and 19.2% in women. HPV 16/18 types were detected in 34.9% of MSM, 17.7% of heterosexual men, and 11.5% of women. Multiple oncogenic HPV (>=2 oncogenic types) rate was 54.6% in MSM, 8.8% in heterosexual men, and 0% in women. In univariate analysis, younger age, male sex, MSM, CD4 <100, HIV viral load >50,000, no administration of HAART, and having >=2 sexually transmitted infections (STIs) were significantly associated with oncogenic HPV infection, whereas higher smoking index and corticosteroid use were marginally associated with oncogenic HPV infection. In multivariate analysis, younger age (OR, 0.98 [0.96-0.99]), MSM (OR, 5.85 [2.33-14.71]), CD4 <100 (OR, 2.24 [1.00-5.01]), and having >=2 STIs (OR, 2.81 [1.72-4.61]) were independently associated with oncogenic HPV infection. These 4 variables were also significant risk factors for multiple oncogenic HPV infection. CONCLUSIONS: Among Japanese HIV-infected patients, approximately two-thirds of MSM, one-fifth of heterosexual men, and one-fifth of women have anal oncogenic HPV infection. Younger age, MSM, >=2 STIs, and immunosuppression confer a higher risk of infection with oncogenic HPV and multiple oncogenic types. PMID- 26368296 TI - Once-daily Mesalamine Formulation for Maintenance of Remission in Ulcerative Colitis: A Randomized, Placebo-controlled Clinical Trial. AB - GOALS: To evaluate the efficacy and safety of mesalamine granules 1.5 g once daily for maintenance of ulcerative colitis (UC) remission. BACKGROUND: Mesalamine is a first-line treatment for induction and maintenance of UC remission. STUDY: A phase 3, randomized, double-blind, placebo-controlled trial of patients with a history of mild to moderate UC, currently in remission, who received mesalamine granules once daily for 6 months. The primary efficacy endpoint was percentage of patients maintaining UC remission at 6 months. RESULTS: A significantly greater percentage of patients receiving mesalamine granules versus placebo were in remission at 6 months (79.9% vs. 66.7%; P=0.03). A greater percentage of patients receiving mesalamine granules maintained a revised Sutherland Disease Activity Index (SDAI)<=2 with no individual component of revised SDAI>1 and rectal bleeding=0 at 6 months (72.0% vs. 58.1%; P=0.04). No significant differences between groups were observed for change from baseline to 6 months for total SDAI score or its components (ie, stool frequency, rectal bleeding, mucosal appearance, physician's rating of disease). Mesalamine granules treatment resulted in a significantly longer remission duration versus placebo (P=0.02) and decreased patients' risk of relapse by 43% (hazard ratio=0.57; 95% confidence interval, 0.35-0.93; P=0.02). Mesalamine granules were well tolerated, and adverse events related to hepatic, renal, and pancreatic function-potential concerns with long-term treatment-occurred at a rate similar to placebo. CONCLUSIONS: Once-daily mesalamine granules are efficacious and safe for the maintenance of UC remission. PMID- 26368297 TI - Antitumor Necrosis Factor-alpha Therapy Is Associated With Reduced Risk of Thromboembolic Events in Hospitalized Patients With Inflammatory Bowel Disease. AB - BACKGROUND: Patients with inflammatory bowel disease (IBD) are at increased risk of thromboembolic events. The aim of this study was to assess whether treatment with anti-tumor necrosis factor-alpha (TNF-alpha) therapy was associated with a decreased risk of thromboembolism. METHODS: We identified IBD patients hospitalized between July 2002 and July 2011 at our institution. Demographic data, medications, indication for hospitalization, and type of thromboembolic event were obtained by chart review. Wald tests were used to calculate an association between clinical characteristics and risk of thromboembolism. A multivariable logistic regression model was used to identify independent risk factors for thromboembolic events. RESULTS: A total of 547 patients (1048 hospitalizations) were identified. Fifty thromboembolic events occurred. Patient related factors associated with thromboembolism included older age (P<0.0001), chronic kidney disease (P=0.001), diabetes (P=0.009), liver disease (P=0.005), and prior history of thromboembolism (P<0.0001). Acute infection (P=0.009), trauma (P=0.009), prolonged hospitalization (P<0.0001), and lack of thromboembolic prophylaxis (P<0.0001) were also associated with increased risk. Systemic corticosteroids were associated with increased risk of thromboembolism (P=0.003), whereas TNF-alpha inhibitors were protective (P=0.011). Multivariate regression identified systemic corticosteroid use (OR=4.62, P=0.0004) as associated with an increased risk of thromboembolism. TNF-alpha inhibitors were associated with a reduced risk of thromboembolism (OR=0.20, P=0.049). CONCLUSIONS: In this cohort of hospitalized IBD patients, TNF-alpha inhibitor therapy was associated with a reduced risk of thromboembolism, whereas systemic corticosteroid use was associated with an increased risk of thromboembolism. PMID- 26368298 TI - Selling Health to the Distracted: Consumer Responses to Source Credibility and Ad Appeal Type in a Direct-to-Consumer Advertisement. AB - Since 1997, when the U.S. Food and Drug Administration first allowed prescription drug companies to release ads directly targeting the public, direct-to-consumer (DTC) advertising has become an integral part of the pharmaceutical industry marketing toolkit, reaching over $4 billion in 2005. In an experiment where cognitive load, a task that requires the investment of a subject's memory in an unrelated task; source credibility; and advertising appeal type (affective or cognitive) were manipulated, attitude toward the ad was measured for a print DTC meningitis vaccine ad. Main effect results for source credibility and advertising appeal type on attitude toward the ad were found, and interactions between manipulated variables were apparent when the individual difference variables related to a specific illness (vaccination history, living in a dorm, family members or friends who had suffered the illness) were taken into account. PMID- 26368299 TI - Subjective Quality Information: Effects of Patient Experience Outcomes and Display Formats on Evaluation and Choice Intentions. AB - This study analyzes the impact of subjective quality information in the form of aggregate patient experience outcomes on respondent evaluation and intended choice of hospitals. We compared clinical performance-based quality measures (i.e., wound infection rates) with participant evaluations and choice intentions when they were additionally provided with subjective quality information (i.e., patient experience outcomes in different display formats). Results suggest that patient experience outcomes significantly affected the evaluations and choice intentions. Additionally, we found significant effects of subjective information display formats. Limitations, directions for future research, and implications for publishing subjective quality information in health care markets are discussed. PMID- 26368300 TI - Advancing Health Marketing Research and Policy Recommendations by Incorporating Source Perspectives. AB - Communication researchers, recognizing the message sent is not necessarily the same as the message received, have incorporated the perspective of advertising professionals into the study of advertising effects. Health marketing research could similarly benefit from incorporating this largely absent perspective into the academic and policy debate surrounding the impact of advertising on health issues ranging from obesity to alcohol use. This commentary serves as a call to action to stakeholders in this academic and policy debate: focus on the perspective of advertising professionals to enrich health marketing and public health research in which advertising is the delivery vehicle for health messages. PMID- 26368301 TI - Helping With All Your Heart: Realistic Heart Stimulus and Compliance With an Organ Donation Request. AB - Pictures and images are important aspects in fundraising advertising and could generate more donations. In two experimental studies, we examined the effect of various pictures of hearts on compliance with a request for organ donations. The solicitor wore a white tee shirt where various forms of hearts were printed: symbolic versus realistic (first experiment), none versus symbolic versus realistic (second experiment). Results showed that more compliance was found in the realistic heart experimental condition whereas the symbolic heart form had no significant effect. PMID- 26368302 TI - The Impact of Demographic Characteristics on Awareness and Usage of Support Groups. AB - There are support groups established for one's emotional and/or physical health; as a result, marketing has appeared in regards to the needs, benefits, and hesitations regarding these groups. This study addresses several types of individuals and situations that lend themselves to using support groups. The authors conducted a study designed to examine demographic characteristics as they relate to a person's decision to go to support groups for health conditions. Looking at the demographics of users and the types of support groups, the authors discuss diverse opportunities for support groups and their organizations to promote communication, improve marketing strategies, and create influential users. PMID- 26368303 TI - Marketing-Stimulated Word-of-Mouth: A Channel for Growing Demand. AB - Marketing-stimulated word-of-mouth (WOM) marketing has been poorly understood in health care, leading to it being underappreciated and underutilized by marketers. A study of new patients to a new runner's clinic was conducted to understand how they chose the program. The importance of marketing-stimulated WOM, both individual and organizational, is documented. Marketing-stimulated WOM is an often overlooked and rarely measured channel for increasing the impact of marketing programs. PMID- 26368304 TI - The effect of 25(OH)D on endothelial and immunological markers in Behcet's disease. AB - BACKGROUND: Endothelial selectine molecules (ESMs) and Toll-like receptors (TLRs) were suggested to be associated with the pathogenesis of Behcet's disease (BD). 25(OH)D deficiency may be associated with endothelial and immune dysfunction. The aim of this study is to investigate the relationship between the 25(OH)D level, and ESMs and TLRs in BD patients. PATIENTS AND METHODS: BD patients were classified as 25(OH)D deficient (Group 1) and sufficient (Group 2) groups. Vitamin D replacement therapy was given to Group 1, after the last replacement dose blood was again collected. ESMs and TLRs levels were evaluated and compared both between Group 1 and Group 2, and pre- and post-treatment measurements of Group 1. RESULTS: The baseline plasma levels of ESMs were significantly higher in Group 1 than in Group 2 (p < 0.05). There were not any significant differences in baseline TLRs levels between Group 1 and Group 2. The mean plasma levels of ESMs were significantly lower in post-replacement assessments (p < 0.05). The mean plasma levels of TLRs were lower in post-replacement assessments, but not significantly (p > 0.05). The active stage disease rate was higher in pre treatment group (36.3%) than post-treatment group (34.6%), but the difference was not significant (p > 0.05). CONCLUSION: Although vitamin D replacement in 25(OH)D deficient BD patients may have some beneficial effects on vascular dysfunction, it cannot be considered the primary treatment modality. PMID- 26368305 TI - The ups and downs of negative (and positive) selection of B cells. AB - Central and peripheral tolerance checkpoints are in place to remove autoreactive B cell populations and prevent the development of autoimmunity. In this issue of the JCI, Pala and colleagues reveal that individuals with the X-linked immunodeficiency Wiskott-Aldrich syndrome (WAS) have opposite alterations at central and peripheral B cell checkpoints: a more stringent selection for central tolerance, resulting in reduced numbers of autoreactive cells at the emergent immature B cell stage, and a relaxed selection for peripheral tolerance, resulting in an increased frequency of autoreactive cells in the mature naive B cell compartment. Moreover, reinstatement of the WAS gene in these patients restored both B cell tolerance checkpoints. These results suggest that, in a normal situation, mature naive B cells undergo a positive selection step driven by self-antigens, kept in control by Tregs. PMID- 26368306 TI - Perhexiline activates KLF14 and reduces atherosclerosis by modulating ApoA-I production. AB - Recent genome-wide association studies have revealed that variations near the gene locus encoding the transcription factor Kruppel-like factor 14 (KLF14) are strongly associated with HDL cholesterol (HDL-C) levels, metabolic syndrome, and coronary heart disease. However, the precise mechanisms by which KLF14 regulates lipid metabolism and affects atherosclerosis remain largely unexplored. Here, we report that KLF14 is dysregulated in the liver of 2 dyslipidemia mouse models. We evaluated the effects of both KLF14 overexpression and genetic inactivation and determined that KLF14 regulates plasma HDL-C levels and cholesterol efflux capacity by modulating hepatic ApoA-I production. Hepatic-specific Klf14 deletion in mice resulted in decreased circulating HDL-C levels. In an attempt to pharmacologically target KLF14 as an experimental therapeutic approach, we identified perhexiline, an approved therapeutic small molecule presently in clinical use to treat angina and heart failure, as a KLF14 activator. Indeed, in WT mice, treatment with perhexiline increased HDL-C levels and cholesterol efflux capacity via KLF14-mediated upregulation of ApoA-I expression. Moreover, perhexiline administration reduced atherosclerotic lesion development in apolipoprotein E-deficient mice. Together, these results provide comprehensive insight into the KLF14-dependent regulation of HDL-C and subsequent atherosclerosis and indicate that interventions that target the KLF14 pathway should be further explored for the treatment of atherosclerosis. PMID- 26368307 TI - Inhibition of hyaluronan synthesis restores immune tolerance during autoimmune insulitis. AB - We recently reported that abundant deposits of the extracellular matrix polysaccharide hyaluronan (HA) are characteristic of autoimmune insulitis in patients with type 1 diabetes (T1D), but the relevance of these deposits to disease was unclear. Here, we have demonstrated that HA is critical for the pathogenesis of autoimmune diabetes. Using the DO11.10xRIPmOVA mouse model of T1D, we determined that HA deposits are temporally and anatomically associated with the development of insulitis. Moreover, treatment with an inhibitor of HA synthesis, 4-methylumbelliferone (4-MU), halted progression to diabetes even after the onset of insulitis. Similar effects were seen in the NOD mouse model, and in these mice, 1 week of treatment was sufficient to prevent subsequent diabetes. 4-MU reduced HA accumulation, constrained effector T cells to nondestructive insulitis, and increased numbers of intraislet FOXP3+ Tregs. Consistent with the observed effects of 4-MU treatment, Treg differentiation was inhibited by HA and anti-CD44 antibodies and rescued by 4-MU in an ERK1/2 dependent manner. These data may explain how peripheral immune tolerance is impaired in tissues under autoimmune attack, including islets in T1D. We propose that 4-MU, already an approved drug used to treat biliary spasm, could be repurposed to prevent, and possibly treat, T1D in at-risk individuals. PMID- 26368309 TI - Behavioral measures of implicit theory of mind in adults with high functioning autism. AB - Theory of mind (ToM) research has shown that adults with high functioning autism (HFA) demonstrate typical performance on tasks that require explicit belief reasoning, despite clear social difficulties in everyday life situations. In the current study, we used implicit belief manipulations that are task-irrelevant and therefore less susceptible to strategies. In a ball-detection task, it was shown that neurotypical individuals detect a ball faster if an agent believed the ball was present. We predicted that adults with high functioning autism (HFA) would not show this effect. While we found a numerical difference in the hypothesized direction, we did not find a reliable group effect. Interestingly, the implicit ToM-index showed a strong negative correlation with both self-reported and observational measures of social difficulties in the HFA group. This suggests that the relationship between implicit ToM reasoning and the symptomatology of HFA might be subtler than assumed. PMID- 26368308 TI - Lentiviral-mediated gene therapy restores B cell tolerance in Wiskott-Aldrich syndrome patients. AB - Wiskott-Aldrich syndrome (WAS) is an X-linked immunodeficiency characterized by microthrombocytopenia, eczema, and high susceptibility to developing tumors and autoimmunity. Recent evidence suggests that B cells may be key players in the pathogenesis of autoimmunity in WAS. Here, we assessed whether WAS protein deficiency (WASp deficiency) affects the establishment of B cell tolerance by testing the reactivity of recombinant antibodies isolated from single B cells from 4 WAS patients before and after gene therapy (GT). We found that pre-GT WASp deficient B cells were hyperreactive to B cell receptor stimulation (BCR stimulation). This hyperreactivity correlated with decreased frequency of autoreactive new emigrant/transitional B cells exiting the BM, indicating that the BCR signaling threshold plays a major role in the regulation of central B cell tolerance. In contrast, mature naive B cells from WAS patients were enriched in self-reactive clones, revealing that peripheral B cell tolerance checkpoint dysfunction is associated with impaired suppressive function of WAS regulatory T cells. The introduction of functional WASp by GT corrected the alterations of both central and peripheral B cell tolerance checkpoints. We conclude that WASp plays an important role in the establishment and maintenance of B cell tolerance in humans and that restoration of WASp by GT is able to restore B cell tolerance in WAS patients. PMID- 26368310 TI - Dissection of autophagy in tobacco BY-2 cells under sucrose starvation conditions using the vacuolar H(+)-ATPase inhibitor concanamycin A and the autophagy-related protein Atg8. AB - Tobacco BY-2 cells undergo autophagy in sucrose-free culture medium, which is the process mostly responsible for intracellular protein degradation under these conditions. Autophagy was inhibited by the vacuolar H(+)-ATPase inhibitors concanamycin A and bafilomycin A1, which caused the accumulation of autophagic bodies in the central vacuoles. Such accumulation did not occur in the presence of the autophagy inhibitor 3-methyladenine, and concanamycin in turn inhibited the accumulation of autolysosomes in the presence of the cysteine protease inhibitor E-64c. Electron microscopy revealed not only that the autophagic bodies were accumulated in the central vacuole, but also that autophagosome-like structures were more frequently observed in the cytoplasm in treatments with concanamycin, suggesting that concanamycin affects the morphology of autophagosomes in addition to raising the pH of the central vacuole. Using BY-2 cells that constitutively express a fusion protein of autophagosome marker protein Atg8 and green fluorescent protein (GFP), we observed the appearance of autophagosomes by fluorescence microscopy, which is a reliable morphological marker of autophagy, and the processing of the fusion protein to GFP, which is a biochemical marker of autophagy. Together, these results suggest the involvement of vacuole type H(+)-ATPase in the maturation step of autophagosomes to autolysosomes in the autophagic process of BY-2 cells. The accumulation of autophagic bodies in the central vacuole by concanamycin is a marker of the occurrence of autophagy; however, it does not necessarily mean that the central vacuole is the site of cytoplasm degradation. PMID- 26368311 TI - Feedback regulation through myosin II confers robustness on RhoA signalling at E cadherin junctions. AB - Actomyosin at the epithelial zonula adherens (ZA) generates junctional tension for tissue integrity and morphogenesis. This requires the RhoA GTPase, which establishes a strikingly stable active zone at the ZA. Mechanisms must then exist to confer robustness on junctional RhoA signalling at the population level. We now identify a feedback network that generates a stable mesoscopic RhoA zone out of dynamic elements. The key is scaffolding of ROCK1 to the ZA by myosin II. ROCK1 protects junctional RhoA by phosphorylating Rnd3 to prevent the cortical recruitment of the Rho suppressor, p190B RhoGAP. Combining predictive modelling and experimentation, we show that this network constitutes a bistable dynamical system that is realized at the population level of the ZA. Thus, stability of the RhoA zone is an emergent consequence of the network of interactions that allow myosin II to feedback to RhoA. PMID- 26368312 TI - A pH-responsive cell-penetrating peptide-modified liposomes with active recognizing of integrin alphavbeta3 for the treatment of melanoma. AB - The use of pH-responsive cell-penetrating peptides (CPPs) is an attractive strategy for drug delivery in vivo, however, they still could not actively target to the desired sites. Here, we designed a pH-responsive CPP (TR) with the ability of active targeting to integrin alphavbeta3, which was a tandem peptide consisted of active targeting ligand peptide (c(RGDfK)) and pH-responsive CPP (TH). The targeting efficiency of TR with integrin was evaluated by molecular simulation and docking studies. The affinity assays of TR peptide modified liposomes (TR Lip) at pH7.4 and pH6.5 demonstrated adequately the pH-responsive binding efficacy of TR-Lip with integrin alphavbeta3. The cellular uptake of CFPE-labeled TR-Lip on integrin alphavbeta3-overexpressing B16F10 cells was 41.67-, 30.67-, and 11.90-fold higher than that of CFPE-labeled PEG-, RGD-, and TH-modified liposomes at pH6.5, respectively, suggesting that TR-Lip could not only actively target to alphavbeta3-overexpressing cells compared to TH-Lip, but also significantly increased cellular uptake compared to RGD-Lip. At the concentration of 20MUg/mL paclitaxel (PTX), the killing activity of PTX-loaded TR-Lip (PTX-TR Lip) against B16F10 cells was 1.80-, 1.45-, 1.30-, 1.15-time higher than that of PTX-loaded PEG-, RGD-, TH-modified liposomes and free PTX at pH6.5, respectively. In vivo imaging displayed the maximum accumulation of DiD-labeled TR-Lip at tumor sites compared to the other groups. Tumor inhibition rate of B16F10 tumor-bearing mice treated with PTX-TR-Lip was 85.04%, relative to that of PBS. In B16F10 tumor bearing mice, PTX-TR-Lip showed significantly higher survival rate compared with the other groups. Collectively, all the results in vitro and in vivo suggested that TR-Lip would be a potential delivery system for PTX to treat integrin alphavbeta3-overexpressing tumor-bearing mice. PMID- 26368313 TI - VEGF therapeutic gene delivery using dendrimer type bio-reducible polymer into human mesenchymal stem cells (hMSCs). AB - The therapeutic potential of mesenchymal stem cells (MSCs) has garnered great attention in the expansive diversity of biomedical research. Despite this broad interest in stem cells, limited incorporation and poor viability are major disadvantages for accomplishing therapeutic success in the field of hMSC-based cell therapy, and an optimal approach for hMSC-based cell therapy using non-viral vectors has not been established. Hence, we examined the possibility of performing gene therapy using the biodegradable polymeric non-viral vector Arginine-grafted poly (cystaminebisacrylamide-diaminohexane) (ABP)-conjugated poly (amidoamine) (PAMAM) dendrimer (PAM-ABP) in hMSCs. PAM-ABP formed compact nanosized polyplexes and showed low cytotoxicity compared to bPEI 25k and Lipofectamine(r) 2000 in hMSCs. Although the cellular uptake was similar, the transfection efficiency and VEGF expression of PAM-ABP using gWiz-Luc and pbeta VEGF were higher than those of the control groups. Although hMSCs were transfected, their stem cell characteristics were retained. Our results suggest that PAM-ABP has the ability to deliver a therapeutic gene in hMSCs. PMID- 26368314 TI - Curtailed two-stage matched pairs design in double-arm Phase II clinical trials. AB - This article proposes a curtailed two-stage matched pairs design to shorten the drug development process in Phase II clinical trials for which there are two arms, a treatment arm and a control arm, and the primary goal being to test whether the treatment is significantly better than the control. The design presented in this article uses the inverse trinomial distribution to determine appropriate cutoff points for the termination or continuation of the trial at each stage and is best suited for trials in which there is a low success rate and the available sample size is limited, such as is the case for trials involving rare forms of cancer or other uncommon diseases. PMID- 26368315 TI - Pressure Modulation of the Enzymatic Activity of Phospholipase A2, A Putative Membrane-Associated Pressure Sensor. AB - Phospholipases A2 (PLA2) catalyze the hydrolysis reaction of sn-2 fatty acids of membrane phospholipids and are also involved in receptor signaling and transcriptional pathways. Here, we used pressure modulation of the PLA2 activity and of the membrane's physical-chemical properties to reveal new mechanistic information about the membrane association and subsequent enzymatic reaction of PLA2. Although the effect of high hydrostatic pressure (HHP) on aqueous soluble and integral membrane proteins has been investigated to some extent, its effect on enzymatic reactions operating at the water/lipid interface has not been explored, yet. This study focuses on the effect of HHP on the structure, membrane binding and enzymatic activity of membrane-associated bee venom PLA2, covering a pressure range up to 2 kbar. To this end, high-pressure Fourier-transform infrared and high-pressure stopped-flow fluorescence spectroscopies were applied. The results show that PLA2 binding to model biomembranes is not significantly affected by pressure and occurs in at least two kinetically distinct steps. Followed by fast initial membrane association, structural reorganization of alpha helical segments of PLA2 takes place at the lipid water interface. FRET-based activity measurements reveal that pressure has a marked inhibitory effect on the lipid hydrolysis rate, which decreases by 75% upon compression up to 2 kbar. Lipid hydrolysis under extreme environmental conditions, such as those encountered in the deep sea where pressures up to the kbar-level are encountered, is hence markedly affected by HHP, rendering PLA2, next to being a primary osmosensor, a good candidate for a sensitive pressure sensor in vivo. PMID- 26368316 TI - Racial and Gender Disparities in the Physician Assistant Profession. AB - OBJECTIVE: To examine whether racial, gender, and ethnic salary disparities exist in the physician assistant (PA) profession and what factors, if any, are associated with the differentials. DATA SOURCES/STUDY SETTING: We use a nationally representative survey of 15,105 PAs from the American Academy of Physician Assistants (AAPA). STUDY DESIGN: We use bivariate and multivariate statistics to analyze pay differentials from the 2009 AAPA survey. PRINCIPLE FINDINGS: Women represent nearly two-thirds of the profession but receive approximately $18,000 less in primary compensation. The differential reduces to just over $9,500 when the analysis includes a variety of other variables. According to AAPA survey, minority PAs tend to make slightly higher salaries than White PAs nationally, although the differences are not statistically significant once the control variables are included in the analysis. CONCLUSIONS: Despite the rough parity in primary salary, PAs of color are vastly underrepresented in the profession. The salaries of women lag in comparison to their male counterparts. PMID- 26368317 TI - Patient Characteristics and Differences in Hospital Readmission Rates. AB - IMPORTANCE: Medicare penalizes hospitals with higher than expected readmission rates by up to 3% of annual inpatient payments. Expected rates are adjusted only for patients' age, sex, discharge diagnosis, and recent diagnoses. OBJECTIVE: To assess the extent to which a comprehensive set of patient characteristics accounts for differences in hospital readmission rates. DESIGN, SETTING, AND PARTICIPANTS: Using survey data from the nationally representative Health and Retirement Study (HRS) and linked Medicare claims for HRS participants enrolled in Medicare who were hospitalized from 2009 to 2012 (n = 8067 admissions), we assessed 29 patient characteristics from survey data and claims as potential predictors of 30-day readmission when added to standard Medicare adjustments of hospital readmission rates. We then compared the distribution of these characteristics between participants admitted to hospitals with higher vs lower hospital-wide readmission rates reported by Medicare. Finally, we estimated differences in the probability of readmission between these groups of participants before vs after adjusting for the additional patient characteristics. MAIN OUTCOMES AND MEASURES: All-cause readmission within 30 days of discharge. RESULTS: Of the additional 29 patient characteristics assessed, 22 significantly predicted readmission beyond standard adjustments, and 17 of these were distributed differently between hospitals in the highest vs lowest quintiles of publicly reported hospital-wide readmission rates (P <= .04 for all comparisons). Almost all of these differences (16 of 17) indicated that participants admitted to hospitals in the highest quintile of readmission rates were more likely to have characteristics that were associated with a higher probability of readmission. The difference in the probability of readmission between participants admitted to hospitals in the highest vs lowest quintile of hospital-wide readmission rates was reduced by 48% from 4.41 percentage points with standard adjustments used by Medicare to 2.29 percentage points after adjustment for all patient characteristics assessed (reduction in difference: 2.12; 95% CI, -3.33 to -0.67; P = .003). CONCLUSIONS AND RELEVANCE: Patient characteristics not included in Medicare's current risk-adjustment methods explained much of the difference in readmission risk between patients admitted to hospitals with higher vs lower readmission rates. Hospitals with high readmission rates may be penalized to a large extent based on the patients they serve. PMID- 26368318 TI - IBX-mediated oxidation of unactivated cyclic amines: application in highly diastereoselective oxidative Ugi-type and aza-Friedel-Crafts reactions. AB - The first o-iodoxybenzoic acid (IBX) mediated oxidation of unactivated amines to imines is described. A range of meso-pyrrolidines were shown to be suitable substrates. The chemical space was further explored with one-pot oxidative Ugi type and aza-Friedel-Crafts reactions, which proved to be highly diastereoselective. PMID- 26368319 TI - Management of side effects of BCR/ABL-negative chronic myeloproliferative neoplasm therapies. Focus on anagrelide. AB - Although hydroxyurea is considered the first-line cytoreductive therapy in high risk patients with polycythemia vera or essential thrombocythemia, approximately 20-25% of patients develop resistance or intolerance and they need an alternative therapy. Anagrelide is the treatment of choice in patients with essential thrombocythemia intolerant or with resistance to hydroxyurea. Anagrelide is usually well tolerated. Although there is concern about the increased risk of cardiac side effects, in most cases these are mild, and easily manageable. In this paper, the available evidence about the management of patients with myeloproliferative neoplasms, with a special focus on the side effects of drug therapies is reviewed. PMID- 26368320 TI - Self-Based Concepts and Obsessive-Compulsive Phenomena. AB - BACKGROUND/AIMS: Using a cognitive framework, this paper examined self perceptions as a vulnerability to phenomena in obsessive-compulsive disorder. Specifically, Guidano and Liotti's model of self-ambivalence (from 1983) and the notion of self-worth contingent upon moral standards were investigated as possible mechanisms to explain how individuals come to notice their unwanted intrusions. METHOD: Using an analogue framework, participants were first-year undergraduate psychology students (95 females, mean age = 22.49 years, SD = 7.96, and 25 males, mean age = 21.64 years, SD = 7.26) who were administered a battery of self-report questionnaires. RESULTS: Results indicated that self-ambivalence moderated the relationship between high moral standards and obsessive-compulsive (OC) phenomena; individuals who had high moral standards and high self ambivalence showed increased OC vulnerability. CONCLUSIONS: The findings suggest that ambivalence about moral self-worth may constitute a particular vulnerability to OC symptoms. Directions for future research are discussed and implications of the findings explored. PMID- 26368321 TI - Performance and complications of lumbar puncture in memory clinics: Results of the multicenter lumbar puncture feasibility study. AB - INTRODUCTION: Lumbar puncture (LP) is increasingly performed in memory clinics. We investigated patient-acceptance of LP, incidence of and risk factors for post LP complications in memory clinic populations. METHODS: We prospectively enrolled 3868 patients (50% women, age 66 +/- 11 years, mini mental state examination 25 +/- 5) at 23 memory clinics. We used logistic regression analysis using generalized estimated equations to investigate risk factors for post-LP complications, such as typical postlumbar puncture headache (PLPH) and back pain. RESULTS: A total of 1065 patients (31%) reported post-LP complaints; 589 patients (17%) reported back pain, 649 (19%) headache, of which 296 (9%) reported typical PLPH. Only few patients needed medical intervention: 11 (0.3%) received a blood patch, 23 (0.7%) were hospitalized. The most important risk factor for PLPH was medical history of headache. An atraumatic needle and age >65 years were preventive. Gender, rest after LP, or volume of cerebrospinal fluid had no effect. DISCUSSIONS: The overall risk of complications is relatively low. If risk factors shown in this study are taken into account, LPs can be safely performed in memory clinics. PMID- 26368322 TI - Metabolomic Analyses of Leishmania Reveal Multiple Species Differences and Large Differences in Amino Acid Metabolism. AB - Comparative genomic analyses of Leishmania species have revealed relatively minor heterogeneity amongst recognised housekeeping genes and yet the species cause distinct infections and pathogenesis in their mammalian hosts. To gain greater information on the biochemical variation between species, and insights into possible metabolic mechanisms underpinning visceral and cutaneous leishmaniasis, we have undertaken in this study a comparative analysis of the metabolomes of promastigotes of L. donovani, L. major and L. mexicana. The analysis revealed 64 metabolites with confirmed identity differing 3-fold or more between the cell extracts of species, with 161 putatively identified metabolites differing similarly. Analysis of the media from cultures revealed an at least 3-fold difference in use or excretion of 43 metabolites of confirmed identity and 87 putatively identified metabolites that differed to a similar extent. Strikingly large differences were detected in their extent of amino acid use and metabolism, especially for tryptophan, aspartate, arginine and proline. Major pathways of tryptophan and arginine catabolism were shown to be to indole-3-lactate and arginic acid, respectively, which were excreted. The data presented provide clear evidence on the value of global metabolomic analyses in detecting species specific metabolic features, thus application of this technology should be a major contributor to gaining greater understanding of how pathogens are adapted to infecting their hosts. PMID- 26368323 TI - Association Mapping of Total Carotenoids in Diverse Soybean Genotypes Based on Leaf Extracts and High-Throughput Canopy Spectral Reflectance Measurements. AB - Carotenoids are organic pigments that are produced predominantly by photosynthetic organisms and provide antioxidant activity to a wide variety of plants, animals, bacteria, and fungi. The carotenoid biosynthetic pathway is highly conserved in plants and occurs mostly in chromoplasts and chloroplasts. Leaf carotenoids play important photoprotective roles and targeted selection for leaf carotenoids may offer avenues to improve abiotic stress tolerance. A collection of 332 soybean [Glycine max (L.) Merr.] genotypes was grown in two years and total leaf carotenoid content was determined using three different methods. The first method was based on extraction and spectrophotometric determination of carotenoid content (eCaro) in leaf tissue, whereas the other two methods were derived from high-throughput canopy spectral reflectance measurements using wavelet transformed reflectance spectra (tCaro) and a spectral reflectance index (iCaro). An association mapping approach was employed using 31,253 single nucleotide polymorphisms (SNPs) to identify SNPs associated with total carotenoid content using a mixed linear model based on data from two growing seasons. A total of 28 SNPs showed a significant association with total carotenoid content in at least one of the three approaches. These 28 SNPs likely tagged 14 putative loci for carotenoid content. Six putative loci were identified using eCaro, five loci with tCaro, and nine loci with iCaro. Three of these putative loci were detected by all three carotenoid determination methods. All but four putative loci were located near a known carotenoid-related gene. These results showed that carotenoid markers can be identified in soybean using extract based as well as by high-throughput canopy spectral reflectance-based approaches, demonstrating the utility of field-based canopy spectral reflectance phenotypes for association mapping. PMID- 26368325 TI - Postsurgical Prophylaxis in Crohn's Disease: Which Patients, Which Agents? AB - Crohn's disease (CD) evolution is characterized by increasing proportions of patients developing complications such as strictures, abscesses and fistulas that require surgical management. After resection of a diseased intestinal segment, CD recurrence concerns up to 60% of patients within a year post surgery. The mucosa just above the site of the intestinal anastomosis is at particularly high risk of relapse. Prophylactic medical therapy to prevent recurrence has been shown to be effective with a variety of medications, but the recurrence rate remains high, demanding that a better risk stratification of patients be achieved. Recognized risk factors for postsurgical CD recurrence include young age at diagnosis and at surgery, smoking, need for repeated surgeries and penetrating disease. These patients require full dose immunosuppressive or anti-tumor necrosis factor (anti TNF) therapy, which should be initiated in the immediate postoperative period, to prevent the onset of an inflammatory activity in the bowel. Systematic follow-up by endoscopy to monitor treatment benefit should also be part of the management, as endoscopic recurrence heralds clinical relapse in these patients. The role of noninvasive markers of mucosal inflammation, such as stool calprotectin levels, show promise to complete this monitoring. Although the efficacy of mesalazine and imidazole antibiotics has been long recognized, more aggressive approaches, such as thiopurines and anti-TNF antibodies, have shown higher efficacies in direct comparison trials. The potential place of anti-homing agents is not yet defined, but these agents should in principle be of interest for this prophylactic indication due to their mode of action and interesting side-effect profile. The current recommendations are based on a step-up approach that includes immunosuppressors and/or imidazole antibiotics, followed by an anti-TNF agent, such as infliximab and adalimumab, both already tested in randomized trials in this indication. When endoscopic recurrence is identified during follow-up, upscaling to anti-TNF or dose escalation is advocated. PMID- 26368326 TI - Human temporal-parietal junction spontaneously tracks others' beliefs: A functional near-infrared spectroscopy study. AB - Humans have the unique capacity to actively reflect on the thoughts, beliefs, and knowledge of others, but do we also track mental states spontaneously when observing other people? We asked this question by monitoring brain activity in belief-sensitive cortex using functional near-infrared spectroscopy (fNIRS) during free-viewing of social videos. More specifically, we identified a portion of the right temporal-parietal junction (rTPJ) selective for mental state processing using an established, explicit theory of mind task, and then analyzed the brain response in that region of interest (ROI) during free-viewing of video clips involving people producing goal-directed actions. We found a significant increase in oxygenated hemoglobin concentration in our rTPJ ROI during free viewing for all of our test videos. Activity in this region was further modulated by the extent to which the knowledge state, or beliefs, of the protagonist regarding the location of an object contrasted with the reality of where the object was hidden. Open-ended questioning suggested our participants were not explicitly focusing on belief states of the characters during free-viewing. Further analyses ruled out lower-level details of the video clips or general attentional differences between conditions as likely explanations for the results. As such, these results call into question the traditional characterization of theory of mind as a resource intensive, deliberate process, and, instead, support an emerging view of theory of mind as a foundation for, rather than the pinnacle of, human social cognition. PMID- 26368328 TI - First Vault Expansion in Apert and Crouzon-Pfeiffer Syndromes: Front or Back? AB - BACKGROUND: Children with Apert and Crouzon-Pfeiffer syndromes are at risk of intracranial hypertension. Until 2005, when the authors switched to occipital expansion, their institution's preferred treatment was fronto-orbital advancement. However, it was still unclear whether (1) occipitofrontal head circumference (i.e., intracranial volume) was greater after occipital expansion than after fronto-orbital advancement; (2) the incidences of tonsillar herniation and papilledema were lower; and (3) visual acuity was better during follow-up. In these patients, the authors therefore compared fronto-orbital advancement with occipital expansion as the first surgical procedure. METHODS: Measurements included repeated occipitofrontal head circumference as a measure for intracranial volume; neuroimaging to evaluate tonsillar herniation; funduscopy to identify papilledema; and visual acuity testing. RESULTS: The authors included 37 patients (Apert syndrome, n = 18; Crouzon-Pfeiffer syndrome, n = 19). Eighteen underwent fronto-orbital advancement and 19 underwent occipital expansion (age at surgery, 1.0 versus 1.5 years; p = 0.13). Follow-up time in both groups was 5.7 years. The increase in occipitofrontal head circumference (+1.09 SD) was greater after occipital expansion than after fronto-orbital advancement (+0.32 SD) (p = 0.03). After occipital expansion, fewer patients with Crouzon-Pfeiffer syndrome had tonsillar herniation (occipital, three of 11; fronto-orbital advancement, seven of eight; p = 0.02); for both syndromes together, fewer patients had papilledema (occipital, four of 19; fronto-orbital advancement, 11 of 18; p = 0.02). Visual acuity was similar after fronto-orbital advancement and occipital expansion (0.09 versus 0.13 logarithm of the minimum angle of resolution) (p = 0.28). CONCLUSIONS: The authors' preference for occipital expansion as the initial craniofacial procedure in Apert and Crouzon-Pfeiffer syndromes is supported by the greater increase it produces in intracranial volume (as evidenced by the occipitofrontal head circumference), which reduces the incidences of tonsillar herniation and papilledema. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III. PMID- 26368324 TI - Integration and Modulation of Intercellular Signaling Underlying Blood Flow Control. AB - Vascular resistance networks control tissue blood flow in concert with regulating arterial perfusion pressure. In response to increased metabolic demand, vasodilation arising in arteriolar networks ascends to encompass proximal feed arteries. By reducing resistance upstream, ascending vasodilation (AVD) increases blood flow into the microcirculation. Once initiated, e.g. through local activation of K(+) channels in endothelial cells (ECs), hyperpolarization is conducted through gap junctions along the endothelium. Via EC projections through the internal elastic lamina, hyperpolarization spreads into the surrounding smooth-muscle cells (SMCs) through myoendothelial gap junctions (MEGJs) to promote their relaxation. Intercellular signaling through electrical signal transmission (i.e. cell-to-cell conduction) can thereby coordinate vasodilation along and among the branches of microvascular resistance networks. Perivascular sympathetic nerve fibers course through the adventitia and release norepinephrine to stimulate SMCs via alpha-adrenoreceptors to produce contraction. In turn, SMCs can signal ECs through MEGJs to activate K(+) channels and attenuate sympathetic vasoconstriction. Activation of K(+) channels along the endothelium will dissipate electrical signal transmission and inhibit AVD, thereby restricting blood flow into the microcirculation while maintaining peripheral resistance and perfusion pressure. This review explores the origins and nature of the intercellular signaling that governs blood flow control in skeletal muscle with respect to the interplay between AVD and sympathetic innervation. Whereas these interactions are integral to daily activity and athletic performance, determining the interplay between respective signaling events provides insight into how selective interventions can improve tissue perfusion and oxygen delivery during vascular disease. PMID- 26368327 TI - Hand Trauma Care in the United States: A Literature Review. AB - BACKGROUND: Hand trauma is one of the most complex injuries treated in the emergency department. Hand trauma injuries are time sensitive and require highly specialized care. Patients may have difficulty accessing appropriate hand trauma care because of a variety of factors. The authors aimed to evaluate the state of the hand trauma system by examining articles that reported on access to hand trauma care. METHODS: The authors conducted a literature review on hand trauma care using the PubMed, Ovid MEDLINE, and Embase databases. The authors included English language articles from the United States that described access to hand trauma care in the emergency health system. RESULTS: Fourteen studies met the authors' inclusion criteria. Ten studies evaluated access to hand trauma care on a patient level. Of these 10 studies, five reported on access to care for transferred patients and five reported on access to care for patients with amputation injuries. The other four studies evaluated access to hand trauma care at a hospital level. CONCLUSIONS: Lack of hand trauma guidelines at emergency departments and a severe shortage of on-call hand specialists at community hospitals and trauma centers have created a suboptimal system of hand emergency care in the United States. The current system of hand trauma care in the United States not only may drive up the cost of care but may also adversely affect patients' health and well-being. PMID- 26368329 TI - Diced Cartilage Grafts Wrapped in Rectus Abdominis Fascia for Nasal Dorsum Augmentation. AB - BACKGROUND: Dorsum augmentation is one of the most delicate components of rhinoplasty. Although various solid grafts have been used in the past for this purpose, diced cartilage grafts wrapped in fascia have become popular in recent decades. In this study, the authors analyze and discuss the results of using diced cartilage grafts wrapped in rectus abdominis muscle fascia for dorsal augmentation. METHODS: Nasal dorsum augmentation using the diced cartilage wrapped in rectus abdominis fascia technique was performed on 109 patients between 2008 and 2014. Six patients were primary cases, 69 patients were secondary, and 18 were tertiary. Sixteen patients had previously undergone more than three operations. In all patients, the rectus abdominis fascia was harvested with the described technique and wrapped around the diced cartilages obtained from the costal cartilage. RESULTS: The average follow-up period was 19.6 months (range, 6 to 47 months). Satisfactory results were obtained with acceptable complications and revision rates. Three patients underwent reoperation because of overcorrection. Insufficient augmentation was seen in five patients. In four patients, infection developed after postoperative day 5. One patient complained of a hypertrophic scar on the donor site. None of the patients showed any symptoms indicating an abdominal hernia. CONCLUSIONS: Techniques using diced cartilage grafts wrapped in fascia have now become the gold standard for dorsal augmentations. When it is considered that secondary cases requiring dorsal augmentation are usually those also needing costal cartilage grafts, rectus abdominis fascia becomes a useful carrier for diced cartilages, which is in the same donor area. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV. PMID- 26368330 TI - Endothelial Cells from Capillary Malformations Are Enriched for Somatic GNAQ Mutations. AB - BACKGROUND: A somatic mutation in GNAQ (c.548G>A; p.R183Q), encoding Galphaq, has been found in syndromic and sporadic capillary malformation tissue. However, the specific cell type containing the mutation is unknown. The purpose of this study was to determine which cells in capillary malformations have the GNAQ mutation. METHODS: Human capillary malformation tissue was obtained from 13 patients during a clinically indicated procedure. Droplet digital polymerase chain reaction, capable of detecting mutant allelic frequencies as low as 0.1 percent, was used to quantify the abundance of GNAQ mutant cells in capillary malformation tissue. Six specimens were fractionated by fluorescence-activated cell sorting into hematopoietic, endothelial, perivascular, and stromal cells. The frequency of GNAQ mutant cells in these populations was quantified by droplet digital polymerase chain reaction. RESULTS: Eight capillary malformations contained GNAQ p.R183Q mutant cells, two lesions had novel GNAQ mutations (p.R183L and p.R183G), and three capillary malformations did not have a detectable GNAQ p.R183 mutation. Mutant allelic frequencies ranged from 2 to 11 percent. Following fluorescence activated cell sorting, the GNAQ mutation was found in the endothelial but not the platelet-derived growth factor receptor-beta-positive cell population; mutant allelic frequencies were 3 to 43 percent. CONCLUSION: Endothelial cells in capillary malformations are enriched for GNAQ mutations and are likely responsible for the pathophysiology underlying capillary malformation. PMID- 26368331 TI - The Impact of Radiation Therapy, Lymph Node Dissection, and Hormonal Therapy on Outcomes of Tissue Expander-Implant Exchange in Prosthetic Breast Reconstruction. AB - BACKGROUND: Total skin-sparing mastectomy, with preservation of the nipple-areola complex, must account for adjuvant medical and surgical treatments for cancer. The authors assessed risk factors for complications after second-stage tissue expander-implant exchange. METHODS: The authors reviewed all institutional total skin-sparing mastectomy cases that had completed tissue expander-implant exchange with at least 3 months of follow-up. They developed multivariate generalized estimating equation models to obtain adjusted relative risks of radiation therapy, type of lymph node dissection, and hormonal therapy in relation to postoperative complications. RESULTS: The authors performed 776 cases in 489 patients, with a median follow-up of 26 months (interquartile range, 10 to 48 months). Radiation therapy was associated with increased wound breakdown risk [relative risk (RR), 3.3; 95 percent CI, 2.0 to 5.7]; infections requiring oral antibiotics (RR, 2.2; 95 percent CI, 1.31 to 3.6), intravenous antibiotics (RR, 6.4; 95 percent CI, 3.9 to 10.7), or procedures (RR, 8.9; 95 percent CI, 4.5 to 17.5); implant exposure (RR, 3.9; 95 percent CI, 1.86 to 8.3); and implant loss (RR, 4.2; 95 percent CI, 2.4 to 7.4). Axillary lymph node dissection was associated with an increased risk of implant loss (RR, 2.0; 95 percent CI, 1.11 to 3.7) relative to sentinel lymph node biopsy. CONCLUSIONS: Axillary lymph node dissection increases the risk of implant loss compared with sentinel lymph node biopsy, independent of radiation therapy. Patients who require axillary lymph node dissection may be encouraged to undergo breast conservation or autologous reconstruction when possible. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III. PMID- 26368332 TI - Olfactory Bulbectomy Leads to the Development of Epilepsy in Mice. AB - There is a clear link between epilepsy and depression. Clinical data demonstrate a 30-35% lifetime prevalence of depression in patients with epilepsy, and patients diagnosed with depression have a three to sevenfold higher risk of developing epilepsy. Traditional epilepsy models partially replicate the clinical observations, with the demonstration of depressive traits in epileptic animals. Studies assessing pro-epileptogenic changes in models of depression, however, are more limited. Here, we examined whether a traditional rodent depression model- bilateral olfactory bulbectomy--predisposes the animals towards the development of epilepsy. Past studies have demonstrated increased neuronal excitability after bulbectomy, but continuous seizure monitoring had not been conducted. For the present study, we monitored control and bulbectomized animals by video-EEG 24/7 for approximately two weeks following the surgery to determine whether they develop spontaneous seizures. All seven bulbectomized mice exhibited seizures during the monitoring period. Seizures began about one week after surgery, and occurred in clusters with severity increasing over the monitoring period. These results suggest that olfactory bulbectomy could be a useful model of TBI-induced epilepsy, with advantages of relatively rapid seizure onset and a high number of individuals developing the disease. The model may also be useful for investigating the mechanisms underlying the bidirectional relationship between epilepsy and depression. PMID- 26368333 TI - Overeating with and without loss of control: Associations with weight status, weight-related characteristics, and psychosocial health. AB - OBJECTIVE: The relative importance of loss of control and overeating in the relationship between binge eating and eating-related and general psychopathology has been debated in the literature. This study assessed the prevalence and correlates of overeating with and without loss of control within a diverse, population-based sample of adolescents. METHOD: A highly diverse (81.1% non White) sample of adolescents (n = 2,793) from EAT-2010 (Eating and Activity in Teens) completed self-report questionnaires assessing eating-related psychopathology, substance use, nonsuicidal self-injury, depressive symptoms, and self-esteem. RESULTS: Overeating without loss of control was reported by 6.9% of girls and 5.0% of boys, while 9.6% of girls and 6.3% of boys reported overeating with loss of control (binge eating). Overall, overeating (with or without loss of control) was positively associated with unhealthy or extreme weight control behaviors, dieting, nonsuicidal self-injury, lower body satisfaction, and self esteem, and higher depressive symptoms relative to no overeating. Among girls, binge eating was associated with unhealthy or extreme weight control behaviors, lower self-esteem, and higher depressive symptoms relative to overeating without loss of control, while in boys, binge eating was associated with greater cigarette usage, lower body satisfaction, and greater depressive symptoms than overeating without loss of control (although cigarette usage was comparable in boys reporting binge eating and no overeating). DISCUSSION: Any overeating, with or without loss of control, was associated with multiple adverse correlates among adolescents. Loss of control was uniquely associated with multiple health indicators, further highlighting its importance as a marker of severity of overeating. PMID- 26368335 TI - Correction: Correction: Mechanism of Inhibition of the Human Sirtuin Enzyme SIRT3 by Nicotinamide: Computational and Experimental Studies. PMID- 26368334 TI - Quantification of epidermal growth factor receptor expression level and binding kinetics on cell surfaces by surface plasmon resonance imaging. AB - Epidermal growth factor receptor (EGFR, also known as ErbB-1 or HER-1) is a membrane bound protein that has been associated with a variety of solid tumors and the control of cell survival, proliferation, and metabolism. Quantification of the EGFR expression level in cell membranes and the interaction kinetics with drugs are thus important for cancer diagnosis and treatment. Here we report mapping of the distribution and interaction kinetics of EGFR in their native environment with the surface plasmon resonance imaging (SPRi) technique. The monoclonal anti-EGFR antibody was used as a model drug in this study. The binding of the antibody to EGFR overexpressed A431 cells was monitored in real time, which was found to follow the first-order kinetics with an association rate constant (ka) and dissociation rate constant (kd) of (2.7 +/- 0.6) * 10(5) M(-1) s(-1) and (1.4 +/- 0.5) * 10(-4) s(-1), respectively. The dissociation constant (KD) was determined to be 0.53 +/- 0.26 nM with up to seven-fold variation among different individual A431 cells. In addition, the averaged A431 cell surface EGFR density was found to be 636/MUm(2) with an estimation of 5 * 10(5) EGFR per cell. Additional measurement also revealed that different EGFR positive cell lines (A431, HeLa, and A549) show receptor density dependent anti-EGFR binding kinetics. The results demonstrate that SPRi is a valuable tool for direct quantification of membrane protein expression level and ligand binding kinetics at single cell resolution. Our findings show that the local environment affects the drug-receptor interactions, and in situ measurement of membrane protein binding kinetics is important. PMID- 26368336 TI - Combination therapy with tamsulosin and solifenacin for male lower urinary tract symptoms with predominant filling symptoms: a new approach to an old problem. AB - Benign prostatic enlargement is the main cause of male lower urinary tract symptoms (LUTS). The distinction and quantification of voiding, storage and postmicturition symptoms help clinicians decide on a modern pharmacological therapeutic approach for male LUTS. Muscarinic receptors antagonists are now considered safe therapy in males and a fixed-dose combination of oral controlled absorbed system solifenacin and tamsulosin is advantageous compared to tamsulosin monotherapy in males with predominant storage symptoms when validated instruments such as International Prostatic Score Symptoms (IPSS) or Total Urgency Frequency Score (TUFS) are used. This combination therapy is well tolerated and maintains symptomatic improvement in the long term. Different options of managing male LUTS with predominant storage symptoms include a combination of tamsulosin and solifenacin, antimuscarinics alone - some with flexible dosing, and the beta-3 agonist mirabegron. Tailored pharmacological therapy for the particular patient is not a reality yet, but judicious use of the different alternatives could bring varied new therapeutic solutions for male LUTS including benign prostatic enlargement and benign prostatic obstruction. PMID- 26368337 TI - Synthesis and Evaluation of Novel Acyclic Nucleoside Phosphonates as Inhibitors of Plasmodium falciparum and Human 6-Oxopurine Phosphoribosyltransferases. AB - Acyclic nucleoside phosphonates (ANPs) are a promising class of antimalarial therapeutic drug leads that exhibit a wide variety of Ki values for Plasmodium falciparum (Pf) and human hypoxanthine-guanine-(xanthine) phosphoribosyltransferases [HG(X)PRTs]. A novel series of ANPs, analogues of previously reported 2-(phosphonoethoxy)ethyl (PEE) and (R,S)-3-hydroxy-2 (phosphonomethoxy)propyl (HPMP) derivatives, were designed and synthesized to evaluate their ability to act as inhibitors of these enzymes and to extend our ongoing antimalarial structure-activity relationship studies. In this series, (S) 3-hydroxy-2-(phosphonoethoxy)propyl (HPEP), (S)-2-(phosphonomethoxy)propanoic acid (CPME), or (S)-2-(phosphonoethoxy)propanoic acid (CPEE) are the acyclic moieties. Of this group, (S)-3-hydroxy-2-(phosphonoethoxy)propylguanine (HPEPG) exhibits the highest potency for PfHGXPRT, with a Ki value of 0.1 MUM and a Ki value for human HGPRT of 0.6 MUM. The crystal structures of HPEPG and HPEPHx (where Hx=hypoxanthine) in complex with human HGPRT were obtained, showing specific interactions with active site residues. Prodrugs for the HPEP and CPEE analogues were synthesized and tested for in vitro antimalarial activity. The lowest IC50 value (22 MUM) in a chloroquine-resistant strain was observed for the bis-amidate prodrug of HPEPG. PMID- 26368338 TI - Five recipient vessels for metachronous chest wall reconstruction: Case report and literature review. AB - Selecting potential recipient vessel options for free flap anastomosis is an important consideration in microsurgical breast and chest wall reconstruction. In these settings, the most common comprise the internal mammary and thoracodorsal vessels, although alternative anastomotic sites have also been described. On occasion, consideration of these alternatives becomes a necessity. The use of five separate recipient vessels is highlighted in a unique case of recurrent locally advanced breast cancer requiring multiple complex reconstructions using free tissue transfer. A 56-year-old lady presented for delayed breast reconstruction one year after radical mastectomy for locally advanced lobular breast cancer. Despite wide resections, local chest-wall recurrence five times necessitated five microsurgical reconstructions, using separate recipient pedicles: internal mammary vessels, thoracodorsal vessels, serratus branch of thoracodorsal vessels, intercostal vessels and thoracoacromial vessels. All flaps survived completely, without donor or recipient complications. There has not been a subsequent recurrence at 6 months since last reconstruction. The purpose of this report is to present the first reported case of microsurgical chest wall reconstruction using five separate free flaps requiring anastomosis to multiple recipient vessels for anterior chest wall coverage, to present a literature-based and clinical review of the regional vascular anatomy of the anterior chest wall, and to present an operative approach algorithm. In such complex cases, this understanding can facilitate a streamlined approach to management. (c) 2014 Wiley Periodicals, Inc. Microsurgery 37:66-70, 2017. PMID- 26368339 TI - Fractal Feature of Particle-Size Distribution in the Rhizospheres and Bulk Soils during Natural Recovery on the Loess Plateau, China. AB - The application of fractal geometry to describe soil structure is an increasingly useful tool for better understanding the performance of soil systems. Only a few studies, however, have focused on the structure of rhizospheric zones, where energy flow and nutrient recycling most frequently occur. We used fractal dimensions to investigate the characteristics of particle-size distribution (PSD) in the rhizospheres and bulk soils of six croplands abandoned for 1, 5, 10, 15, 20, and 30 years on the Loess Plateau of China and evaluated the changes over successional time. The PSDs of the rhizospheres and the fractal dimensions between rhizosphere soil and bulk soils during the natural succession differed significantly due to the influence of plant roots. The rhizospheres had higher sand (0.05-1.00 mm) contents, lower silt (<0.002 mm) contents, and lower fractal dimensions than the bulk soils during the early and intermediate successional stages (1-15 years). The fractal dimensions of the rhizosphere soil and bulk soil ranged from 2.102 to 2.441 and from 2.214 to 2.459, respectively, during the 30 year restoration. Rhizospheric clay and silt contents and fractal dimension tended to be higher and sand content tended to be lower as abandonment age increased, but the bulk soils had the opposite trend. Linear regression analysis indicated that the fractal dimensions of both the rhizospheres and bulk soils were significantly linearly correlated with clay, sand, organic-carbon, and total nitrogen contents, with R2 ranging from 0.526 to 0.752 (P<0.001). In conclusion, PSD differed significantly between the rhizosphere soil and bulk soil. The fractal dimension was a sensitive and useful index for quantifying changes in the properties of the different soil zones. This study will greatly aid the application of the fractal method for describing soil structure and nutrient status and the understanding of the performance of rhizospheric zones during ecological restoration. PMID- 26368340 TI - Hypothesis-Driven Treatment of Naming Deficits. AB - This article proposes to use information processing models of cognition to guide behaviorally based treatments of language deficits, specifically, single-word object naming. Our approach is illustrated with a clinical case of a transcortical sensory aphasic. Clinical neuropsychological and functional imaging data demonstrate that the components comprising the information processing network that underpins naming can be mapped onto a cerebral neural network in the neurologically intact and that reorganization of function seen in transcortical sensory aphasia can demonstrate plasticity in this neural network. The observed balance of impaired and preserved clinical and physiological components in reorganizing neural networks such as this can be used to design treatment strategies to alleviate naming deficits. PMID- 26368341 TI - Linking Treatment to Outcomes through Teams: Building a Conceptual Model of Rehabilitation Effectiveness. AB - The team approach has been the dominant paradigm in contemporary inpatient medical rehabilitation. In this article, a conceptual model of treatment effectiveness is presented that links characteristics of the hospital organization, treatment, and participants to patient outcomes through the treatment team. The proposed mechanism of team process is founded on the interprofessional relations and "personality" (or social climate) of the team. The process of team care emerges from team leadership and managerial practices. The dimensions of team process that are hypothesized to influence patient outcomes are highlighted. PMID- 26368342 TI - The Role of the Environment in Fostering Independence: Conceptual and Methodological Issues in Developing an Instrument. AB - Although rehabilitation professionals are increasingly aware that environments can support or interfere with an individual's ability to function, environmental factors are not emphasized in assessment and intervention planning across rehabilitation disciplines. Conceptual and methodological issues related to creating a measure for assessing the rehabilitation environment, in either institutional or home settings, as it relates to fostering an individual's independence are presented. Reflecting a multidimensional conceptual base, the Environment-Independence Interaction Scale has subscales for temporal, physical, social, and cultural dimensions of the environment. The measure is primarily intended for research in evaluating effects of various rehabilitation environments on selected outcomes. PMID- 26368343 TI - Longitudinal Assessment of Stroke Survivors' Handicap. AB - Proxy agreement for telephone administration of the Craig Handicap Assessment and Reporting Technique (CHART) to community-living individuals 18 months poststroke and their caregivers was assessed and compared to in-person interview of the same sample 1 year earlier. Proxy agreement was adequate for a summary score and for all but one of the dimensions (social integration), replicating prior findings. Physical independence, mobility, and occupation dimensions were intercorrelated. Scores for these dimensions at 6 months poststroke predicted later scores. The study contributes to the validity of the CHART, especially the physical independence, mobility, and occupation dimensions. PMID- 26368344 TI - Stroke Rehabilitation in Nursing Homes. AB - Increasing numbers of stroke patients with profound functional, psychological, and cognitive impairments are receiving rehabilitation in Medicare skilled nursing facilities. These facilities vary substantially in the patients they admit, the volume and intensity of therapy they provide, and the outcomes they achieve. Facilities with an orientation toward rehabilitation and community discharge providing more intensive therapy services by a wider range of skilled professionals have better outcomes. PMID- 26368345 TI - Stroke Transition after Inpatient Rehabilitation. AB - This article describes a 3-year study testing the efficacy of a system of home based, case-managed care for stroke survivors returning to the community following inpatient poststroke rehabilitation. The Stroke Transition after Inpatient Rehabilitation (STAIR) study was a randomized, controlled trial of a postdischarge management strategy carried out in a group of 55 stroke patients, aged 65 or older, who did not have serious residual cognitive or language impairments and returned to the community following inpatient rehabilitation with the assistance of a primary caregiver. The program was shown to facilitate improvement in the general social activity level of the patients in the experimental group at 6 months compared to the control, and there was a trend for this effect to persist at 1 year. Strong relationships were identified between residual disability, social activity level, patients' perceptions of efficacy, and caregiver stress. PMID- 26368346 TI - Are We Measuring All the Right Things? PMID- 26368347 TI - Picking Up the Pieces of My Life: Aftermath of a Stroke. PMID- 26368348 TI - Nucleophilic Aromatic Substitution Reactions in Water Enabled by Micellar Catalysis. AB - Given the huge dependence on dipolar, aprotic solvents such as DMF, DMSO, DMAc, and NMP in nucleophilic aromatic substitution reactions (SNAr), a simple and environmentally friendly alternative is reported. Use of a "benign-by-design" nonionic surfactant, TPGS-750-M, in water enables nitrogen, oxygen, and sulfur nucleophiles to participate in SNAr reactions. Aromatic and heteroaromatic substrates readily participate in this micellar catalysis, which takes place at or near ambient temperatures. PMID- 26368351 TI - Association Between Angiotensin Receptor Blockers and Longitudinal Decline in Tau in Mild Cognitive Impairment. PMID- 26368352 TI - Fragile X-Associated Tremor/Ataxia Syndrome in a Man in His 30s. PMID- 26368353 TI - Rheumatoid Meningitis Presenting With Multiple Strokelike Episodes. PMID- 26368354 TI - Targeted Temperature Management for Cardiac Arrest. PMID- 26368355 TI - Targeted Temperature Management for Cardiac Arrest--Reply. PMID- 26368356 TI - Considerations of Long-term Pain Evaluation Post-Deep Brain Stimulation Surgery. PMID- 26368357 TI - Considerations of Long-term Pain Evaluation Post- Deep Brain Stimulation Surgery Reply. PMID- 26368361 TI - Stereospecific Synthesis of alpha- and beta-Hydroxyalkyl P-Stereogenic Phosphine Boranes and Functionalized Derivatives: Evidence of the P=O Activation in the BH3 -Mediated Reduction. AB - Access to hydroxy-functionalized P-chiral phosphine-boranes has become an important field in the synthesis of P-stereogenic compounds used as ligands in asymmetric catalysis. A family of optically pure alpha and beta-hydroxyalkyl tertiary phosphine-boranes has been prepared by using a three-step procedure from readily accessible enantiopure adamantylphosphinate, obtained by semi-preparative HPLC on multigram scale. Firstly, a two-step one-pot transformation affords the enantiopure hydroxyalkyl tertiary phosphine oxides in good yields and enantioselectivities. The third step, BH3 -mediated reduction, allows the formation of the desired phosphine-boranes with excellent stereospecifity. The mechanistic study of this reduction provides new evidence to elucidate the crucial role of the pendant hydroxy group and the subsequent activation of the P=O bond by the boron atom. PMID- 26368360 TI - Does deficiency of von Willebrand factor protect against cardiovascular disease? Analysis of a national discharge register. AB - INTRODUCTION: von Willebrand factor (VWF) plays a critical role in platelet adhesion and aggregation after vascular injury and at sites of high shear rate. Elevated VWF levels are associated with an increased risk of ischemic cardiovascular events; however, it is unclear whether VWF deficiency is protective against atherosclerosis. We aimed to compare the prevalence of cardiovascular disease (CVD) among patients with and without von Willebrand disease (VWD). METHODS: A cross-sectional analysis was performed on discharge data for adults from the Nationwide Inpatient Sample (NIS) between the years 2009 and 2011. CVD was defined as ischemic heart disease, myocardial infarction, ischemic cerebrovascular disease, or peripheral vascular disease. For prevalence calculations and statistical analyses, we used discharge-level weights provided by the NIS to reflect national estimates. CVD was compared across groups by use of the Rao-Scott chi-square test. Multivariable logistic regression was used to estimate the likelihood of CVD in VWD patients after adjustment for age, gender, and CVD-related risk factors. RESULTS: The prevalence of CVD in VWD patients was less than the prevalence of CVD in non-VWD patients (15.0% versus 26.0%). VWD was associated with a decreased likelihood of CVD after adjustment for age, gender, and CVD-related risk factors (odds ratio 0.85; 95% confidence interval 0.79 0.92). DISCUSSION: These findings indicate that the risk of CVD is decreased among VWD patients, and that VWF deficiency may be protective against CVD. PMID- 26368362 TI - Quasi-phase-matched four-wave mixing generation between C-band and mid-infrared regions using a symmetric hybrid plasmonic waveguide grating. AB - A symmetric hybrid plasmonic waveguide (SHPW) configuration based on quasi-phase matched (QPM) four-wave mixing (FWM) is proposed to realize efficient FWM conversion between the C-band and mid-infrared (mid-IR) regions. Due to the ability to allow strong confinement of light, an extremely large nonlinear parameter gamma>104 m-1 W-1 and a very low propagation loss ~3*10-3 dB/MUm accompanying the sub-lambda scale (effective mode area Aeff~3*10-2 MUm2) are achieved by optimally designing the SHPW geometrical parameters. In addition, a QPM technique is adopted to achieve a relatively long effective length of FWM nonlinear process by constructing a long SHPW grating, thereby resulting in highly efficient wavelength conversion without rigorous dispersion engineering of waveguide structures. By using numerical simulations we have demonstrated that, for a pump wavelength of 1,800 nm, an efficient and flat FWM conversion of ~-17 dB (~-22 dB) could be realized around a target signal wavelength of the C-band: 1,530-1,565 nm (mid-IR: 2,118-2,180 nm), in a 1,000 MUm-long grating with a serious phase mismatch. PMID- 26368363 TI - Parametric distortion-adaptive neighborhood for omnidirectional camera. AB - Catadioptric omnidirectional images exhibit serious nonlinear distortion due to the involved quadratic mirror. Conventional pinhole model-based methods perform poorly when directly applied to the deformed omnidirectional images. This study constructs a catadioptric geometry system to analyze the variation of the neighborhood of an object in terms of the elevation and azimuth directions in a spherical coordinate system. To accurately represent the distorted visual information, a parametric neighborhood mapping model is proposed based on the catadioptric geometry. Unlike the conventional catadioptric models, the prior information of the system is effectively integrated into the neighborhood formulation framework. Then the distortion-adaptive neighborhood can be directly calculated based on its measurable image radial distance. This method can significantly improve the computational efficiency of algorithm since statistical neighborhood sampling is not used. On the basis of the proposed neighborhood model, a distortion-invariant Haar wavelet transform is presented to perform the robust human detection and tracking in catadioptric omnidirectional vision. The experimental results verify the effectiveness of the proposed neighborhood mapping model and prove that the distorted neighborhood in the omnidirectional image follows a nonlinear pattern. PMID- 26368364 TI - Modeling of surface topography in single-point diamond turning machine. AB - Surface roughness is an important factor in characterizing the performance of high-precision optical surfaces. In this paper, we propose a model to estimate the surface roughness generated by a single-point diamond turning machine. In this model, we take into consideration the basic tool-cutting parameters as well as the relative vibration between the tool and the workpiece in both the infeed and feeding directions. Current models focus on the relative tool-workpiece vibration in the infeed direction. However, based on our experimental measurements, the contribution of relative tool-workpiece vibration in the feeding direction is significant and cannot be ignored in the model. The proposed model is able to describe the surface topography for flat as well as cylindrical surfaces of the workpiece. It has the potential to describe more complex spherical surfaces or freeform surfaces. Our experimental study with metal materials shows good correlation between the model and the diamond-turned surfaces. PMID- 26368365 TI - Investigation on the response of fused taper couplers to ultrasonic wave. AB - The responses of fused taper couplers with different structure parameters to ultrasonic waves have been investigated theoretically and experimentally. A comprehensive analysis of the acousto-optic interaction was presented, taking into account the elasto-optic geometric effect. It is found that direct deformation of the coupler induced by ultrasonic waves is the critical factor in the sensing mechanism and is closely related to the sensor sensitivity. Moreover, the strain response of the coupler with different structure parameters was analyzed using a 3D coupled acoustic-solid numerical model, which was based on the developed mathematical model. According to the theoretical analyses, related experiments were carried out, and experimental results show that this ultrasonic sensor with a longer stretching length has higher sensitivity and the sensitivity of the sensor takes a nonmonotonic relation with an aspect ratio, which are consistent with the theoretical analyses results. We argue that our work may provide a useful guide in designing and optimizing more sensitive ultrasonic sensors used in practical ultrasonic detection. PMID- 26368366 TI - Speckle-suppressed phase-only holographic three-dimensional display based on double-constraint Gerchberg-Saxton algorithm. AB - The Gerchberg-Saxton (GS) algorithm is widely used to calculate the phase-only computer-generated hologram (CGH) for holographic three-dimensional (3D) display. However, speckle noise exists in the reconstruction of the CGH due to the uncontrolled phase distribution. In this paper, we propose a method to suppress the speckle noise by simultaneously reconstructing the desired amplitude and phase distribution. The phase-only CGH is calculated by using a double-constraint GS algorithm, in which both the desired amplitude and phase information are constrained in the image plane in each iteration. The calculated phase-only CGH can reconstruct the 3D object on multiple planes with a desired amplitude distribution and uniform phase distribution. Thus the speckle noise caused by the phase fluctuation between adjacent pixels is suppressed. Both simulations and experiments are presented to demonstrate the effective speckle noise suppression by our algorithm. PMID- 26368367 TI - Exploring the physics of efficient optical trapping of dielectric nanoparticles with ultrafast pulsed excitation. AB - Stable optical trapping of dielectric nanoparticles with low power high repetition-rate ultrafast pulsed excitation has received considerable attention in recent years. However, the exact role of such excitation has been quite illusive so far since, for dielectric micron-sized particles, the trapping efficiency turns out to be similar to that of continuous-wave excitation and independent of pulse chirping. In order to provide a coherent explanation of this apparently puzzling phenomenon, we justify the superior role of high-repetition rate pulsed excitation in dielectric nanoparticle trapping which is otherwise not possible with continuous-wave excitation at a similar average power level. We quantitatively estimate the optimal combination of pulse peak power and pulse repetition rate leading to a stable trap and discuss the role of inertial response on the dependence of trapping efficiency on pulse width. In addition, we report gradual trapping of individual quantum dots detected by a stepwise rise in a two-photon fluorescence signal from the trapped quantum dots which conclusively proves individual particle trapping. PMID- 26368368 TI - Registering functional defects into periodic holographic structures. AB - In this paper, we present two methods for registering desired defect lattices within background periodic lattices through spatial light-modulator-based holographic lithography. In the first method, the diffraction efficiency from the engineered phase pattern was used to locally modify the fill fraction of polymerized materials in holographic structures, and, at the same time, we achieved the lattice matching between modified and background regions. In the second method, we registered spatially variant lattices for a 90 deg bend within the background periodic lattices through two steps of phase engineering of the laser beam. PMID- 26368369 TI - High laser efficiency and photostability of pyrromethene dyes mediated by nonpolar solvent. AB - Many pyrromethene (PM) dyes have been shown to outperform established rhodamine dyes in terms of laser efficiency in the green-yellow spectral region, but their rapid photochemical degradation in commonly used ethanol or methanol solvents continues to limit its use in high average power liquid dye lasers. A comparative study on narrowband laser efficiency and photostability of commercially available PM567 and PM597 dyes, using nonpolar n-heptane and 1,4-dioxane and polar ethanol solvents, was carried out by a constructed pulsed dye laser, pumped by the second harmonic (532 nm) radiation of a Q-switched Nd:YAG laser. Interestingly, both nonpolar solvents showed a significantly higher laser photostability (~100 times) as well as peak efficiency (~5%) of these PM dyes in comparison to ethanol. The different photostability of the PM dyes was rationalized by determining their triplet-state spectra and capability to generate reactive singlet oxygen (O21) by energy transfer to dissolved oxygen in these solvents using pulse radiolysis. Heptane is identified as a promising solvent for these PM dyes for use in high average power dye lasers, pumped by copper vapor lasers or diode pumped solid-state green lasers. PMID- 26368370 TI - Study of the two-photon excitation of photoinitiator in various solvents, and the two-photon polymerization process. AB - In this study, the two-photon absorption excited fluorescence of the photosensitizer 4,4'-Bis(diethylamino)benzophenonin in different solvents is investigated by using mode-locked Ti:sapphire excitation having a wavelength of 800 nm with pulse duration of 150 fs at the rate of 1 kHz. The fluorescence signals excited by wavelengths of 800 and 400 nm have been compared. Contribution of these cross-section measurements for the two-photon polymerization processes is also reported. PMID- 26368371 TI - Metallically coated dielectric rectangle resonator. AB - The double transfer matrix method (DTMM) is proposed for calculating the eigenvalues of the resonant mode of a metallically coated dielectric rectangle resonator. Two-dimensional electromagnetic analyses are performed to investigate the optical influences induced by planar structure parameters. The results show that there theoretically exists a highest Q-factor resonance for both TE and TM modes at a certain length-width ratio with fixed resonant wavelength and resonator area. Due to the influence of surface plasma polaritons (SPPs) trapped at the corners of the resonator which is not considered in DTMM, the TM mode resonances are deformed and deviate severely from that of the analytical model. The geometric deformation on the resonator is introduced by replacing the four right angles with circular boundaries, and the SPP accompanied mode behaviors are corrected to the standing waves. PMID- 26368372 TI - Fast two-dimensional fluorescence correlation spectroscopy technique for tea quality detection. AB - A fast two-dimensional fluorescence correlation spectroscopy technique based on light emitting diodes is developed, which uses light intensity and excitation wavelength as quickly changeable and easily controllable external perturbations. A compact and automatic system is set up to detect tea quality. A partial least square regression method is used to create predictive models for tea grades. Compared to the traditional fluorescence spectroscopy method, this convenient two dimensional correlation spectroscopy technique is more accurate according to our experimental results and is promising for practical applications. PMID- 26368373 TI - Elliptic cylindrical silicon nanowire hybrid surface plasmon polariton waveguide. AB - We researched an elliptic cylindrical silicon nanowire hybrid surface plasmon polariton waveguide and evaluated its mode characteristics using the finite element method software COMSOL. The waveguide consists of three parts: an elliptic cylindrical silicon nanowire, a silver film layer, and a silica covering layer between them. All of the components are surrounded by air. After optimizing the geometrical parameters of the waveguide, we can achieve the waveguide's strong field confinement (ranging from lambda2/270 to lambda2/27) and long propagation distances (119-485 MUm). In order to further understand the impact of the waveguide's architecture on its performance, we also studied the ridge hybrid waveguide. The results show that the ridge waveguide has moderate local field confinement ranging from lambda2/190 to lambda2/20 and its maximum propagation distance is about 340 MUm. We compared the elliptic cylindrical and ridge nanowire hybrid waveguides with the cylindrical hybrid waveguide that we studied before. The elliptic cylindrical waveguide achieves a better trade-off between reasonable mode confinement and maximum propagation length in the three waveguides. The researched hybrid surface plasmon polaritons waveguides are useful to construct devices such as a directional coupler and may find potential applications in photonic integrated circuits or other novel SPP devices. PMID- 26368374 TI - Extending generalized Kubelka-Munk to three-dimensional radiative transfer. AB - The generalized Kubelka-Munk (gKM) approximation is a linear transformation of the double spherical harmonics of order one (DP1) approximation of the radiative transfer equation. Here, we extend the gKM approximation to study problems in three-dimensional radiative transfer. In particular, we derive the gKM approximation for the problem of collimated beam propagation and scattering in a plane-parallel slab composed of a uniform absorbing and scattering medium. The result is an 8*8 system of partial differential equations that is much easier to solve than the radiative transfer equation. We compare the solutions of the gKM approximation with Monte Carlo simulations of the radiative transfer equation to identify the range of validity for this approximation. We find that the gKM approximation is accurate for isotropic scattering media that are sufficiently thick and much less accurate for anisotropic, forward-peaked scattering media. PMID- 26368375 TI - Analysis of stationary power/amplitude distributions for multiple channels of sampled FBGs. AB - Stationary power/amplitude distributions for multiple channels of the sampled fiber Bragg grating (SFBG) along the grating length are analyzed. Unlike a uniform FBG, the SFBG has multiple channels in the reflection spectrum, not a single channel. Thus, the stationary power/amplitude distributions for these multiple channels are analyzed by using two different theoretical models. In the first model, the SFBG is regarded as a set of grating sections and non-grating sections, which are alternately stacked. A step-like distribution is obtained for the corresponding power/amplitude of each channel along the grating length. While, in the second model, the SFBG is decomposed into multiple uniform "ghost" gratings, and a continuous distribution is obtained for each ghost grating (i.e., each channel). After a comparison, the distributions obtained in the two models are identical, and the equivalence between the two models is demonstrated. In addition, the impacts of the duty cycle on the power/amplitude distributions of multiple channels of SFBG are presented. PMID- 26368376 TI - Noncontact full-angle fluorescence molecular tomography system based on rotary mirrors. AB - We propose a novel noncontact fluorescence molecular tomography system that achieves full-angle capacity with the use of a new rotary-mirrors-based imaging head. In the imaging head, four plane mirrors are mounted on a rotating gantry to enable illumination and detection over 360 degrees . In comparison with existing full-angle systems, our system does not require rotation of the specimen animal, a large and heavy light source (with scanning head), or a bulky camera (with filters and lens). The system design and implementation are described in detail. Both physical phantom and in vivo experiments are performed to verify the performance of the proposed system. PMID- 26368377 TI - Q-switched 1329 nm Nd:CNGG laser. AB - We demonstrate a laser-diode-pumped Q-switched 1329 nm neodymium-doped calcium niobium-gallium-garnet (Nd:CNGG) laser using a V:YAG crystal as a saturable absorber. An average output power of 353 mW and a repetition rate of 13.43 kHz for Q-switched pulses were obtained. The pulse width was from 124 to 151.4 ns under different pump powers. Output power of 685 mW was obtained without the V:YAG crystal inserted. PMID- 26368378 TI - High data rate transient sensing using dielectric micro-resonator. AB - An approach to high-speed tracking of optical mode shifts of microresonators for wide-bandwidth sensing applications is presented. In the typical microresonator sensor, the whispering gallery optical modes (WGM) are excited by tangentially coupling tunable laser light into the resonator cavity, such as a microsphere. The light coupling is achieved by overlapping the evanescent field of the cavity with that of a prism or the tapered section of a single-mode optical fiber. The transmission spectrum through the fiber is observed to detect WGM shifts as the laser is tuned across a narrow wavelength range. High data rate transient-sensing applications require the tuning of the diode laser at high repetition rates and tracking of the WGM shifts. At high repetition rates, the thermal inertia prevents appropriate tuning of the laser, thus leading to smaller tuning ranges and waveform distortions. In the present paper, the laser is tuned using a harmonic (rather than ramp or triangular) waveform, and its output is calibrated at various input frequencies and amplitudes using a Fabry-Perot interferometer to account for the tuning range variations. The WGM shifts are tracked by performing a modified cross-correlation method on the transmission spectra. Force sensor experiments were performed using ramp and harmonic waveform tuning of the diode laser with rates up to 10 kHz. Results show that the harmonic tuning of the laser eliminates the high-speed transient thermal effects. The thermal model developed to predict the laser tuning agrees well the experiments. PMID- 26368379 TI - Characterization of dual-polarization LTE radio over a free-space optical turbulence channel. AB - A dual polarization (DP) radio over a free-space optical (FSO) communication link using a long-term evolution (LTE) radio signal is proposed and analyzed under different turbulence channel conditions. Radio signal transmission over the DP FSO channel is experimentally verified by means of error vector magnitude (EVM) statistics. We demonstrate that such a system, employing a 64 quadrature amplitude modulation at the frequency bands of 800 MHz and 2.6 GHz, evinces reliability with <8% of EVM in a turbulent channel. Based on the results, we show that transmitting the LTE signal over the FSO channel is a potential solution for last-mile access or backbone networks, when using multiple-input multiple-output based DP signals. PMID- 26368380 TI - Wavelength dependence for silicon-wafer temperature measurement by autocorrelation-type frequency-domain low-coherence interferometry. AB - We investigate silicon wafer temperature measurement characteristics based on optical low-coherence interferometry by altering the light source wavelength. Variations in Si wafer optical thickness with temperature are expressed by thermal expansion and the refractive index. The optical characteristics determine the measurement precision and range. In this study, the measurement precision and the measurable temperature range were evaluated for three wavelengths: 1040, 1310, and 1550 nm. The maximum measurable temperature at 1040 nm was the lowest because of signal light absorption caused by fundamental interband absorption. The measurement precision at 1040 nm was the highest at 0.020 degrees C because optical thickness changes per degree C increase with decreasing wavelength. PMID- 26368381 TI - Evaluation of low-cadmium ZnCdSeS alloyed quantum dots for remote phosphor solid state lighting technology. AB - We report on the possibility to enhance color rendering of commercially available remote phosphor light-emitting diode modules by using low-cadmium content ZnCdSeS alloyed quantum dots. The employed numerical simulations showed that the color rendering index of 90+ at the color-correlated temperature of 3200 K can be achieved by application of a single layer of quantum dots onto a neutral-white remote phosphor substrate. The experimental results fully support the numerical calculations, thus revealing the only limiting factor in achieving a higher photometric performance: the self-absorption effect in quantum dots. The presented low-cadmium content quantum dots allow a price-effective upgrade of already existing remote phosphor solid-state lighting technology toward a higher color-rendering capability. PMID- 26368382 TI - Sensitivity analysis for oblique incidence reflectometry using Monte Carlo simulations. AB - Oblique incidence reflectometry has developed into an effective, noncontact, and noninvasive measurement technology for the quantification of both the reduced scattering and absorption coefficients of a sample. The optical properties are deduced by analyzing only the shape of the reflectance profiles. This article presents a sensitivity analysis of the technique in turbid media. Monte Carlo simulations are used to investigate the technique and its potential to distinguish the small changes between different levels of scattering. We present various regions of the dynamic range of optical properties in which system demands vary to be able to detect subtle changes in the structure of the medium, translated as measured optical properties. Effects of variation in anisotropy are discussed and results presented. Finally, experimental data of milk products with different fat content are considered as examples for comparison. PMID- 26368383 TI - Time-series methods in analysis of the optical tweezers recordings. AB - In this paper we treat optical tweezers as discrete-time linear filters and analyze the recorded trajectories of the trapped beads using time-series methods. Using these techniques we obtain a simple analytical formula for the aliased power-spectrum density. Moreover, we separate influences of the noise and blur induced by the video camera from the physical content of the measurements, providing simple tools to detect and account for these distortions. Finally, checking how our tools work on the real data, we identify what parameters of video camera calibration the blur is dominating and what the additive noise is dominating. We also detect a range where these two distortions cancel each other so that the data can be mistakenly classified as undisturbed. PMID- 26368384 TI - Manipulative attack using the phase retrieval algorithm for double random phase encoding. AB - A novel attack scheme is proposed based on a phase retrieval algorithm. In the scheme, the attacker interferes with the user's normal communication through wiretapping the channel and falsifying the ciphertext and quickly cracks the system by gathering information. The difference of this attack scheme from previous schemes is the dispensability of certain assumptions, which results in a higher value of practical application and further significance of the research. In this paper, the double random phase encoding is taken as an example to verify the validity of the scheme. The results show that our proposed scheme is feasible and efficient. PMID- 26368385 TI - 760 fs diode-pumped mode-locked laser with Yb:LuAG crystal at 1032 nm. AB - In this study, we experimentally demonstrate the generation of 760 fs pulse duration from a diode-pumped Yb:LuAG mode-locked laser at 1032 nm. At the repetition rate of 58.6 MHz, the maximum average power of 1.07 W was obtained, corresponding to the peak power of 24 kW. To our knowledge, these results represent the shortest pulse duration and highest peak power ever obtained for a 1032 nm mode-locked laser with Yb:LuAG crystal. PMID- 26368386 TI - Effect of wall pressure and shear stress on embedded cylindrical microlasers. AB - In this paper, we carried out numerical experiments to study the effect of the shear stress and the wall pressure on the optical mode shift of two embedded cylindrical microlasers. The optical cavities (laser) are encapsulated in a slab that is clamped at the bottom surface while the other sides of the slab are free stress boundaries. When a uniform shear stress and pressure is applied on the top surfaces of the slab, the morphology of the optical resonators are perturbed. This leads to a shift in the optical modes [commonly referred to as the whispering gallery mode (WGM)] of the resonators. The effect of the geometry (size and position of the optical cavities) and materials properties on the optical mode shift are studied. The results show a linear dependency of the WGM shift on the applied external pressure. In addition, the optical mode shift is slightly dependent on the geometry and the material properties. The effect of the shear stress on the WGM shift shows a quadratic dependency and this nonlinearity is strongly dependent on the position of the resonators within the slab. The studies also show that the proposed configuration could be used as a sensor for simultaneous measurements of wall pressure and shear stress. PMID- 26368387 TI - Silicon hybrid plasmonic microring resonator for sensing applications. AB - A novel silicon hybrid plasmonic microring resonator consisting of a silver nanoring on top of a silicon-on-insulator ring is proposed and investigated theoretically for possible applications in sensing at the deep subwavelength scale. By using the finite-element method, insight into how the mode properties (Q factor, effective mode volume, energy ratio, sensitivity) depend on the geometric structure of the hybrid microring resonator is presented. Simulation results reveal that this kind of hybrid microcavity maintains a high Q factor ~600, an ultrasmall mode volume of 0.15 MUm3, and high sensitivity of 497 nm/refractive index unit for refractive index sensing. The hybrid plasmonic microcavity with optimized geometric structures presented provides the potential for ultracompact sensing applications. PMID- 26368388 TI - Surface measurement of indium tin oxide thin film by wavelength-tuning Fizeau interferometry. AB - Indium-tin oxide (ITO) thin films have been widely used in displays such as liquid crystal displays and touch panels because of their favorable electrical conductivity and optical transparency. The surface shape and thickness of ITO thin films must be precisely measured to improve their reliability and performance. Conventional measurement techniques take single point measurements and require expensive systems. In this paper, we measure the surface shape of an ITO thin film on top of a transparent plate using wavelength-tuning Fizeau interferometry. The surface shape was determined by compensating for the phase error introduced by optical interference from the thin film, which was calculated using the phase and amplitude distributions measured by wavelength-tuning. The proposed measurement method achieved noncontact, large-aperture, and precise measurements of transparent thin films. The surface shape of the sample was experimentally measured to an accuracy of 5.13 nm. PMID- 26368389 TI - Lesson in creativity: editorial. AB - Editor-in-Chief Ron Driggers shares lessons in creativity from Dr. Harold Szu. PMID- 26368390 TI - Pi-Extended Ethynyl 21,23-Dithiaporphyrins: A Synthesis and Comparative Study of Electrochemical, Optical, and Self-Assembling Properties. AB - 21,23-Dithiaporphyrins were synthesized containing pi-extending ethynyl substituents at the meso positions. These porphyrins displayed highly bathochromic and broadened absorbance profiles spanning 400-900 nm with molar absorptivities ranging from 2500 to 300,000 M(-1) cm(-1). Electrochemically, these ethynyl dithiaporphyrins undergo a single oxidation at 0.44 or 0.57 V and reduction at -1.17 or -1.08 V versus a ferrocene/ferrocenium internal standard depending on the type of functionalization appended to the ethynyl group. DFT calculations predict that the delocalization of the frontier molecular orbitals should expand onto the meso positions of the ethynyl 21,23-dithiaporphyrins; shrinking the HOMO-LUMO energy gap by destabilizing the HOMO energy. Indeed, the DFT results agree with our optical and electrochemical assessments. Finally, differential scanning calorimetry combined with cross-polarized optical microscopy and powder X-ray diffraction was used to assess the ability of these porphyrins for long-range order. For the ethynylphenyl alkoxy 21,23 dithiaporphyin, birefringent, soft-crystalline-like domains were observed by polarized microscopy, which are marginally sustained by a low-level of crystallinity detected in the XRD, suggesting that long-range ordering is possible. Overall, ethynyl 21,23-dithiaporphyrins are able to harvest much lower energy light and possess lower oxidation and reduction potentials compared to their pyrrolic analogues, which are desirable properties for applications in organic electronics. PMID- 26368392 TI - Emission Projections for Long-Haul Freight Trucks and Rail in the United States through 2050. AB - This work develops an integrated model approach for estimating emissions from long-haul freight truck and rail transport in the United States between 2010 and 2050. We connect models of macroeconomic activity, freight demand by commodity, transportation networks, and emission technology to represent different pathways of future freight emissions. Emissions of particulate matter (PM), carbon monoxide (CO), nitrogen oxides (NOx), and total hydrocarbon (THC) decrease by 60% 70% from 2010 to 2030, as older vehicles built to less-stringent emission standards retire. Climate policy, in the form of carbon tax that increases apparent fuel prices, causes a shift from truck to rail, resulting in a 30% reduction in fuel consumption and a 10%-28% reduction in pollutant emissions by 2050, if rail capacity is sufficient. Eliminating high-emitting conditions in the truck fleet affects air pollutants by 20% to 65%; although these estimates are highly uncertain, they indicate the importance of durability in vehicle engines and emission control systems. Future infrastructure investment will be required both to meet transport demand and to enable actions that reduce emissions of air and climate pollutants. By driving the integrated model framework with two macroeconomic scenarios, we show that the effect of carbon tax on air pollution is robust regardless of growth levels. PMID- 26368391 TI - The Functional Study of the N-Terminal Region of Influenza B Virus Nucleoprotein. AB - Influenza nucleoprotein (NP) is a major component of the ribonucleoprotein (vRNP) in influenza virus, which functions for the transcription and replication of viral genome. Compared to the nucleoprotein of influenza A (ANP), the N-terminal region of influenza B nucleoprotein (BNP) is much extended. By virus reconstitution, we found that the first 38 residues are essential for viral growth. We further illustrated the function of BNP by mini-genome reconstitution, fluorescence microscopy, electron microscopy, light scattering and gel shift. Results show that the N terminus is involved in the formation of both higher homo oligomers of BNP and BNP-RNA complex. PMID- 26368393 TI - Characterization of a Novel Butachlor Biodegradation Pathway and Cloning of the Debutoxylase (Dbo) Gene Responsible for Debutoxylation of Butachlor in Bacillus sp. hys-1. AB - Bacillus sp. strain hys-1, which was isolated from active sludge, could degrade >90% butachlor at a concentration of 100 mg/L within 7 days. The present work revealed that strain hys-1 could mineralize butachlor via the following pathway: butachlor was initially metabolized to 2-chloro-N-(2,6-diethylphenyl)-N methylacetamide by debutoxylation and then transformed to form 2-chloro-N-(2,6 diethylphenyl)acetamide by N-demethylation. Subsequently, it was converted to 2,6 diethylaniline and further mineralized into CO2 and H2O. In addition, the catalytic efficiency of crude cell extracts descended as follows: alachlor > acetochlor > butachlor. Furthermore, a novel 744 bp gene responsible for transforming butachlor into 2-chloro-N-(2,6-diethylphenyl)-N-methylacetamide was cloned from strain hys-1 and the encoding debutoxylase was designated Dbo. Then Dbo was expressed in Escherichia coli BL21 (DE3) and purified using Ni nitrilotriacetic acid affinity chromatography. Dbo displayed the highest activity against butachlor at pH 6.5 and 30 degrees C. Metal ions played an important role in Dbo activity. To the best of the authors' knowledge, this is the first report that strain hys-1 can mineralize butachlor by a novel metabolic mechanism and the first identification of a gene encoding butachlor debutoxylase. PMID- 26368394 TI - Catalytic Cyclization of o-Alkynyl Phenethylamines via Osmacyclopropene Intermediates: Direct Access to Dopaminergic 3-Benzazepines. AB - A novel osmium-catalyzed cyclization of o-alkynyl phenethylamines to give 3 benzazepines is reported. The procedure allows the straightforward preparation of a broad range of dopaminergic 3-benzazepine derivatives. Mechanistic investigations revealed that the process takes place via osmacyclopropene intermediates, which were isolated and characterized by X-ray crystallography. PMID- 26368395 TI - Diurnal Human Activity and Introduced Species Affect Occurrence of Carnivores in a Human-Dominated Landscape. AB - Diurnal human activity and domestic dogs in agro-forestry mosaics should theoretically modify the diurnal habitat use patterns of native carnivores, with these effects being scale-dependent. We combined intensive camera trapping data with Bayesian occurrence probability models to evaluate both diurnal and nocturnal patterns of space use by carnivores in a mosaic of land-use types in southern Chile. A total of eight carnivores species were recorded, including human-introduced dogs. During the day the most frequently detected species were the culpeo fox and the cougar. Conversely, during the night, the kodkod and chilla fox were the most detected species. The best supported models showed that native carnivores responded differently to landscape attributes and dogs depending on both the time of day as well as the spatial scale of landscape attributes. The positive effect of native forest cover at 250 m and 500 m radius buffers was stronger during the night for the Darwin's fox and cougar. Road density at 250 m scale negatively affected the diurnal occurrence of Darwin's fox, whereas at 500 m scale roads had a stronger negative effect on the diurnal occurrence of Darwin's foxes and cougars. A positive effect of road density on dog occurrence was evidenced during both night and day. Patch size had a positive effect on cougar occurrence during night whereas it affected negatively the occurrence of culpeo foxes and skunks during day. Dog occurrence had a negative effect on Darwin's fox occurrence during day-time and night-time, whereas its negative effect on the occurrence of cougar was evidenced only during day-time. Carnivore occurrences were not influenced by the proximity to a conservation area. Our results provided support for the hypothesis that diurnal changes to carnivore occurrence were associated with human and dog activity. Landscape planning in our study area should be focused in reducing both the levels of diurnal human activity in native forest remnants and the dispersion rates of dogs into these habitats. PMID- 26368396 TI - Failed Replication of Oxytocin Effects on Trust: The Envelope Task Case. AB - The neurohormone Oxytocin (OT) has been one of the most studied peptides in behavioral sciences over the past two decades. Many studies have suggested that OT could increase trusting behaviors. A previous study, based on the "Envelope Task" paradigm, where trust is assessed by the degree of openness of an envelope containing participant's confidential information, showed that OT increases trusting behavior and reported one of the most powerful effects of OT on a behavioral variable. In this paper we present two failed replications of this effect, despite sufficient power to replicate the original large effect. The non significant results of these two failed replications clearly exclude a large effect of OT on trust in this paradigm but are compatible with either a null effect of OT on trust, or a small effect, undetectable with small sample size (N = 95 and 61 in Study 1 and 2, respectively). Taken together, our results question the purported size of OT's effect on trust and emphasize the need for replications. PMID- 26368397 TI - Enhanced 2,3-Butanediol Production by Optimizing Fermentation Conditions and Engineering Klebsiella oxytoca M1 through Overexpression of Acetoin Reductase. AB - Microbial production of 2,3-butanediol (2,3-BDO) has been attracting increasing interest because of its high value and various industrial applications. In this study, high production of 2,3-BDO using a previously isolated bacterium Klebsiella oxytoca M1 was carried out by optimizing fermentation conditions and overexpressing acetoin reductase (AR). Supplying complex nitrogen sources and using NaOH as a neutralizing agent were found to enhance specific production and yield of 2,3-BDO. In fed-batch fermentations, 2,3-BDO production increased with the agitation speed (109.6 g/L at 300 rpm vs. 118.5 g/L at 400 rpm) along with significantly reduced formation of by-product, but the yield at 400 rpm was lower than that at 300 rpm (0.40 g/g vs. 0.34 g/g) due to acetoin accumulation at 400 rpm. Because AR catalyzing both acetoin reduction and 2,3-BDO oxidation in K. oxytoca M1 revealed more than 8-fold higher reduction activity than oxidation activity, the engineered K. oxytoca M1 overexpressing the budC encoding AR was used in fed-batch fermentation. Finally, acetoin accumulation was significantly reduced by 43% and enhancement of 2,3-BDO concentration (142.5 g/L), yield (0.42 g/g) and productivity (1.47 g/L/h) was achieved compared to performance with the parent strain. This is by far the highest titer of 2,3-BDO achieved by K. oxytoca strains. This notable result could be obtained by finding favorable fermentation conditions for 2,3-BDO production as well as by utilizing the distinct characteristic of AR in K. oxytoca M1 revealing the nature of reductase. PMID- 26368398 TI - Intellectual property rights and challenges for development of affordable human papillomavirus, rotavirus and pneumococcal vaccines: Patent landscaping and perspectives of developing country vaccine manufacturers. AB - The success of Gavi, the Vaccine Alliance depends on the vaccine markets providing appropriate, affordable vaccines at sufficient and reliable quantities. Gavi's current supplier base for new and underutilized vaccines, such as the human papillomavirus (HPV), rotavirus, and the pneumococcal conjugate vaccine is very small. There is growing concern that following globalization of laws on intellectual property rights (IPRs) through trade agreements, IPRs are impeding new manufacturers from entering the market with competing vaccines. This article examines the extent to which IPRs, specifically patents, can create such obstacles, in particular for developing country vaccine manufacturers (DCVMs). Through building patent landscapes in Brazil, China, and India and interviews with manufacturers and experts in the field, we found intense patenting activity for the HPV and pneumococcal vaccines that could potentially delay the entry of new manufacturers. Increased transparency around patenting of vaccine technologies, stricter patentability criteria suited for local development needs and strengthening of IPRs management capabilities where relevant, may help reduce impediments to market entry for new manufacturers and ensure a competitive supplier base for quality vaccines at sustainably low prices. PMID- 26368399 TI - Seasonal influenza vaccine dose distribution in 195 countries (2004-2013): Little progress in estimated global vaccination coverage. AB - Seasonal influenza is an important disease which results in 250,000-500,000 annual deaths worldwide. Global targets for vaccination coverage rates (VCRs) in high-risk groups are at least 75% in adults >=65 years and increased coverage in other risk groups. The International Federation of Pharmaceutical Manufacturers and Associations Influenza Vaccine Supply (IFPMA IVS) International Task Force developed a survey methodology in 2008, to assess the global distribution of influenza vaccine doses as a proxy for VCRs. This paper updates the previous survey results on absolute numbers of influenza vaccine doses distributed between 2004 and 2013 inclusive, and dose distribution rates per 1000 population, and provides a qualitative assessment of the principal enablers and barriers to seasonal influenza vaccination. The two main findings from the quantitative portion of the survey are the continued negative trend for dose distribution in the EURO region and the perpetuation of appreciable differences in scale of dose distribution between WHO regions, with no observed convergence in the rates of doses distributed per 1000 population over time. The main findings from the qualitative portion of the survey were that actively managing the vaccination program in real-time and ensuring political commitment to vaccination are important enablers of vaccination, whereas insufficient access to vaccination and lack of political commitment to seasonal influenza vaccination programs are likely contributing to vaccination target failures. In all regions of the world, seasonal influenza vaccination is underutilized as a public health tool. The survey provides evidence of lost opportunity to protect populations against potentially serious influenza-associated disease. We call on the national and international public health communities to re-evaluate their political commitment to the prevention of the annual influenza disease burden and to develop a systematic approach to improve vaccine distribution equitably. PMID- 26368401 TI - T-shaped single-photon router. AB - We study the transport properties of a single photon scattered by a two-level system (TLS) in a T-shaped waveguide, which is made of two coupled-resonator waveguides (CRWs)- an infinite CRW and a semi-infinite CRW. The spontaneous emission of the TLS directs single photons from one CRW to the other. Although the transfer rate is different for the wave incident from different CRWs, due to the boundary breaking the translational symmetry, the boundary can enhance the transfer rate found in Phys. Rev. Lett. 111, 103604 (2013) and Phys. Rev. A 89, 013805 (2014), as the transfer rate could be unity for the wave incident from the semi-infinite CRW. PMID- 26368402 TI - Simultaneous monitoring the real and imaginary parts of the analyte refractive index using liquid-core photonic bandgap Bragg fibers. AB - We demonstrate simultaneous monitoring of the real and imaginary parts of the liquid analyte refractive index by using a hollow-core Bragg fiber. We apply this two-channel fiber sensor to monitor concentrations of various commercial cooling oils. The sensor operates using spectral monitoring of the fiber bandgap center wavelength, as well as monitoring of the fiber transmission amplitude at mid bandgap position. The sensitivity of the fiber sensor to changes in the real part of the core refractive index is found to be 1460nm/Refractive index unit (RIU). By using spectral modality and effective medium theory, we determine the concentrations of the two commercial fluids from the measured refractive indices with an accuracy of ~0.57% for both low- and high-loss oils. Moreover, using an amplitude-based detection modality allows determination of the oil concentration with accuracy of ~1.64% for low-loss oils and ~2.81% for the high-loss oils. PMID- 26368403 TI - Analysis of the modal evolution in fused-type mode-selective fiber couplers. AB - Fused-type mode-selective fiber couplers exciting the LP(11) mode are fabricated by well-defined fiber cladding reduction, pretapering and fusion. At a wavelength of 905 nm 80 % of the injected power in the single-mode fiber was transmitted in the few-mode fiber selectively exciting the LP(11) mode. The coupling behavior was experimentally investigated for the case of strong as well as weak fusion. Numerical simulations based on the super-mode coupling approach were used to estimate fabrication parameters and to discuss the modal evolution in arbitrarily fused couplers. The influence of changes in the coupler geometry on the super modes and their modal weighting are analyzed by calculations of the effective refractive index and by modal decomposition. PMID- 26368400 TI - Sequence-Dependent Conformational Heterogeneity and Proton-Transfer Reactivity of the Fluorescent Guanine Analogue 6-Methyl Isoxanthopterin (6-MI) in DNA. AB - The local conformations of individual nucleic acid bases in DNA are important components in processes fundamental to gene regulation. Fluorescent nucleic acid base analogues, which can be substituted for natural bases in DNA, can serve as useful spectroscopic probes of average local base conformation and conformational heterogeneity. Here we report excitation-emission peak shift (EES) measurements of the fluorescent guanine (G) analogue 6-methyl isoxanthoptherin (6-MI), both as a ribonucleotide monophosphate (NMP) in solution and as a site-specific substituent for G in various DNA constructs. Changes in the peak positions of the fluorescence spectra as a function of excitation energy indicate that distinct subpopulations of conformational states exist in these samples on time scales longer than the fluorescence lifetime. Our pH-dependent measurements of the 6-MI NMP in solution show that these states can be identified as protonated and deprotonated forms of the 6-MI fluorescent probe. We implement a simple two-state model, which includes four vibrationally coupled electronic levels to estimate the free energy change, the free energy of activation, and the equilibrium constant for the proton transfer reaction. These parameters vary in single stranded and duplex DNA constructs, and also depend on the sequence context of flanking bases. Our results suggest that proton transfer in 6-MI-substituted DNA constructs is coupled to conformational heterogeneity of the probe base, and can be interpreted to suggest that Watson-Crick base pairing between 6-MI and its complementary cytosine in duplex DNA involves a "low-barrier-hydrogen-bond". These findings may be important in using the 6-MI probe to understand local base conformational fluctuations, which likely play a central role in protein-DNA and ligand-DNA interactions. PMID- 26368404 TI - Quantitative monitoring of the level of singlet oxygen using luminescence spectra of phosphorescent photosensitizer. AB - The lack of accurate and robust photodynamic therapy dosimetry is one of the obstacles for the widespread clinical applications. In this study, we propose a methodology to monitor the production of reactive oxygen species in real-time using the phosphorescent spectra of metalloporphyrin based photosensitizer. The correlation among the phosphorescence intensity, the (1)O(2) quantum yield (Phi(Delta)) and the oxygen concentration [O(2)] was established. A method of determining Phi(Delta) with different [O(2)] was studied based on comparative spectrophotometry, and the quantum yield Phi(Delta) of gadolinium metalated hematoporphyrin mono ether (Gd-HMME) in methanol was determined for different [O(2)]. With our method, both [O(2)] and Phi(Delta) could be monitored simultaneously using the phosphorescence spectra. The photochemical reactions in a liquid phantom composed of Gd-HMME and (1)O(2) capture 1,3 diphenylisobenzofuran (DPBF) were correlated using the kinetics equations of singlet oxygen generation and reaction. Using our method, the (1)O(2) quantum yield becomes observable and the (1)O(2) dose rate could be calculated by the product of photosensitizer absorption and its (1)O(2) quantum yield. Moreover, this (1)O(2) dosimetry could be observed by spectral imaging intuitively without complex analysis, and is especially suitable for precise customized photodynamic treatment. PMID- 26368405 TI - Equivalent refractive-index structure constant of non-Kolmogorov turbulence. AB - The relationship between the non-Kolmogorov refractive-index structure constant and the Kolmogorov refractive-index structure constant is derived by using the refractive-index structure function and the variance of refractive-index fluctuations. It shows that the non-Kolmogorov structure constant is proportional to the Kolmogorov structure constant and the scaling factor depends on the outer scale and the spectral power law. For a fixed Kolmogorov structure constant, the non-Kolmogorov structure constant increases with a increasing outer scale for the power law less than 11/3, the trend is opposite for the power law greater than 11/3. This equivalent relation provides a way of obtaining the non-Kolmogorov structure constant by using the Kolmogorov structure constant. PMID- 26368406 TI - Precise measurement of single-mode fiber lengths using a gain-switched distributed feedback laser with delayed optical feedback. AB - A simple method to measure single-mode optical fiber lengths is proposed and demonstrated using a gain-switched 1.55-MUm distributed feedback laser without a fast photodetector or an optical interferometer. From the variation in the amplified spontaneous emission noise intensity with respect to the modulation frequency of the gain switching, the optical length of a 1-km single-mode fiber immersed in water is found to be 1471.043915 m +/- 33 MUm, corresponding to a relative standard deviation of 2.2 * 10(-8). This optical length is an average value over a measurement time of one minute under ordinary laboratory conditions. PMID- 26368407 TI - Environmental coherence and excitation effects in non-Markovian dynamics. AB - We study the non-Markovian dynamics of a qubit system coupled respectively to coherent state, squeezing vacuum state, and mixed state environments through dephasing interaction. Special attention is paid to the problem of environmental coherence and excitation on the effect of non-Markovianity of system dynamics. Some nontrivial and unexpected results are found. The number of environmental excitations serves to enhance the non-Markovianity of system dynamics, but the enhancement slows down with the increasing of the variance of excitation number. However, environmental coherence can play dual effects, which enhances in some cases and suppresses in other cases the non-Markovianity of system dynamics. PMID- 26368409 TI - High power L-band mode-locked fiber laser based on topological insulator saturable absorber. AB - We demonstrate a passive mode-locked Er:Yb doped double-clad fiber laser using a microfiber-based topological insulator (Bi(2)Se(3)) saturable absorber (TISA). By optimizing the cavity loss and output coupling ratio, the mode-locked fiber laser can operate in L-band with high average output power. With the highest pump power of 5 W, 91st harmonic mode locking of soliton bunches with average output power of 308 mW was obtained. This is the first report that the TISA based erbium-doped fiber laser operating above 1.6 MUm and is also the highest output power yet reported in TISA based passive mode-locked fiber laser. PMID- 26368408 TI - High-speed adaptive optics for imaging of the living human eye. AB - The discovery of high frequency temporal fluctuation of human ocular wave aberration dictates the necessity of high speed adaptive optics (AO) correction for high resolution retinal imaging. We present a high speed AO system for an experimental adaptive optics scanning laser ophthalmoscope (AOSLO). We developed a custom high speed Shack-Hartmann wavefront sensor and maximized the wavefront detection speed based upon a trade-off among the wavefront spatial sampling density, the dynamic range, and the measurement sensitivity. We examined the temporal dynamic property of the ocular wavefront under the AOSLO imaging condition and improved the dual-thread AO control strategy. The high speed AO can be operated with a closed-loop frequency up to 110 Hz. Experiment results demonstrated that the high speed AO system can provide improved compensation for the wave aberration up to 30 Hz in the living human eye. PMID- 26368410 TI - Performance evaluation of data center service localization based on virtual resource migration in software defined elastic optical network. AB - Data center interconnection with elastic optical network is a promising scenario to meet the high burstiness and high-bandwidth requirements of data center services. In our previous work, we implemented cross stratum optimization of optical network and application stratums resources that allows to accommodate data center services. In view of this, this study extends the data center resources to user side to enhance the end-to-end quality of service. We propose a novel data center service localization (DCSL) architecture based on virtual resource migration in software defined elastic data center optical network. A migration evaluation scheme (MES) is introduced for DCSL based on the proposed architecture. The DCSL can enhance the responsiveness to the dynamic end-to-end data center demands, and effectively reduce the blocking probability to globally optimize optical network and application resources. The overall feasibility and efficiency of the proposed architecture are experimentally verified on the control plane of our OpenFlow-based enhanced SDN testbed. The performance of MES scheme under heavy traffic load scenario is also quantitatively evaluated based on DCSL architecture in terms of path blocking probability, provisioning latency and resource utilization, compared with other provisioning scheme. PMID- 26368411 TI - High-Q lithium niobate microdisk resonators on a chip for efficient electro-optic modulation. AB - Lithium niobate (LN) microdisk resonators on a LN-silica-LN chip were fabricated using only conventional semiconductor fabrication processes. The quality factor of the LN resonator with a 39.6-MUm radius and a 0.5-MUm thickness is up to 1.19 * 10(6), which doubles the record of the quality factor 4.84 * 10(5) of LN resonators produced by microfabrication methods allowing batch production. Electro-optic modulation with an effective resonance-frequency tuning rate of 3.0 GHz/V was demonstrated in the fabricated LN microdisk resonator. PMID- 26368412 TI - Spectral domain optical coherence tomography with balanced detection using single line-scan camera and optical delay line. AB - We propose a spectral domain optical coherence tomography (SD-OCT) system that uses a single line-scan detection scheme for balanced detection. Two phase opposed spectra, generated by two optical fiber couplers, were detected by using a spectrometer with fast optical switching. A 2.69 km optical fiber was introduced to provide a proper time delay to prevent phase errors caused by the difference in measurement time between the two opposing spectra and unstable output voltages for controlling the galvano-scanner. Hence, a phase difference of pi was obtained between the spectra over the sample depth without a phase error, which improved sensitivity by approximately 6 dB compared to that of conventional SD-OCT. We directly showed and compared the OCT images before and after applying the proposed balanced detection method in a phantom and in vivo sample. PMID- 26368413 TI - Multi-filter transport of intensity equation solver with equalized noise sensitivity. AB - Phase retrieval based on the Transport of Intensity Equation (TIE) has shown to be a powerful tool to obtain the phase of complex fields. Recently, it has been proven that the performance of TIE techniques can be improved when using unequally spaced measurement planes. In this paper, an algorithm is presented that recovers accurately the phase of a complex objects from a set of intensity measurements obtained at unequal plane separations. This technique employs multiple band-pass filters in the frequency domain of the axial derivative and uses these specific frequency bands for the calculation of the final phase. This provides highest accuracy for TIE based phase recovery giving minimal phase error for a given set of measurement planes. Moreover, because each of these band-pass filters has a distinct sensitivity to noise, a new plane selection strategy is derived that equalizes the error contribution of all frequency bands. It is shown that this new separation strategy allows controlling the final error of the retrieved phase without using a priori information of the object. This is an advantage compared to previous optimum phase retrieval techniques. In order to show the stability and robustness of this new technique, we present the numerical simulations. PMID- 26368414 TI - Aerosol absorption measurement at SWIR with water vapor interference using a differential photoacoustic spectrometer. AB - Atmospheric aerosol plays an important role in atmospheric radiation balance through absorbing and scattering the solar radiation, which changes local weather and global climate. Accurate measurement is highly requested to estimate the radiative effects and climate effects of atmospheric aerosol. Photoacoustic spectroscopy (PAS) technique, which observes the aerosols on their natural suspended state and is insensitive to light scattering, is commonly recognized as one of the best candidates to measure the optical absorption coefficient (OAC) of aerosols. In the present work, a method of measuring aerosol OAC at the wavelength where could also be absorbed by water vapor was proposed and corresponding measurements of the absorption properties of the atmospheric aerosol at the short wave infrared (SWIR, 1342 nm) wavelength were carried out. The spectrometer was made up of two high performance homemade photoacoustic cells. To improve the sensitivity, several methods were presented to control the noise derived from gas flow and vibration from the sampling pump. Calibration of the OAC and properties of the system were also studied in detail. Using the established PAS instrument, measurement of the optical absorption properties of the atmospheric aerosol were carried out in laboratory and field environment. PMID- 26368415 TI - Accurate modelling of fabricated hollow-core photonic bandgap fibers. AB - We report a novel approach to reconstruct the cross-sectional profile of fabricated hollow-core photonic bandgap fibers from scanning electron microscope images. Finite element simulations on the reconstructed geometries achieve a remarkable match with the measured transmission window, surface mode position and attenuation. The agreement between estimated scattering loss from surface roughness and measured loss values indicates that structural distortions, in particular the uneven distribution of glass across the thin silica struts on the core boundary, have a strong impact on the loss. This provides insight into the differences between idealized models and fabricated fibers, which could be key to further fiber loss reduction. PMID- 26368416 TI - Orbital-angular-momentum crosstalk and temporal fading in a terrestrial laser link using single-mode fiber coupling. AB - Using a mobile experimental testbed, we perform a series of measurements on the detection of laser beams carrying orbital angular momentum (OAM) to evaluate turbulent channel distortions and crosstalk among receive states in an 84-m roofed optical link. We find that a receiver assembly using single-mode fiber coupling serves as a good signal selector in terms of crosstalk rejection. From the recorded temporal channel waveforms, we estimate average crosstalk profiles and propose an appropriate probability density function for the fluctuations of the detected OAM signal. Further measurements of OAM crosstalk are described for a horizontal 400-m link established over our campus. PMID- 26368417 TI - 100-Gb/s 2R regeneration using cross gain compression in semiconductor optical amplifiers. AB - All-optical 2R regeneration of 100-Gb/s on-off-keying (OOK) signal is experimentally demonstrated based on cross gain compression (XGC) effect in semiconductor optical amplifiers (SOAs). It is shown that a high-quality logic inverted signal and SOAs with faster gain recovery times are the two key enabling factors for obtaining regeneration results at such speeds. BER improvement of 1.2~2 dB is experimentally obtained at 1551 nm and regenerative results are demonstrated on a wide wavelength range from 1535 nm to 1555 nm. The tolerance of the input signal to optical signal-to-noise ratio (OSNR) deterioration is also experimentally studied for the 2R regeneration scheme at two different wavelengths. PMID- 26368418 TI - New method to measure liquid diffusivity by analyzing an instantaneous diffusion image. AB - A novel optical method was applied to measure the binary liquid diffusion coefficient (D) quickly. Equipped with an asymmetric liquid-core cylindrical lens (ALCL), the spatially resolving ability of the ALCL in measuring refractive index of liquid was utilized to obtain the gradient distribution of the liquid concentration along diffusive direction. Based on Fick's second law, the D value was then calculated by analyzing diffusion images. It was worth mentioning that only one instantaneous diffusive image was required to measure D value by the method, reducing the measurement time greatly from several hours in traditional methods to a few seconds. The diffusion coefficients of ethylene glycol diffusing in pure water, at temperatures from 288.15 to 308.15 K, were measured by analyzing instantaneous diffusion images, the results were consistent well with the values measured by using holographic interferometry and Taylor dispersion methods. The method is characterized by faster measurement, direct observation of diffusive process, and easy operation, which provides a new method in measuring diffusion coefficient of liquids rapidly. PMID- 26368419 TI - Design of a femtogram scale double-slot photonic crystal optomechanical cavity. AB - We present the design of a double-slot photonic crystal cavity as an optomechanical device which contains a nanomechanical resonator with an effective mass as small as 6.91 fg. The optical Q-factor is optimized to 2 * 10(5). Using phononic crystals, the mechanical vibration is confined in a small volume to form a mechanical mode of 4 GHz with a high mechanical Q-factor and a femtogram effective mass. The localized mechanical mode overlaps with the optical field and strengthens the optomechanical coupling with a vacuum optomechanical coupling rate g0/2pi exceeding 600 kHz. Considering fabrication imperfections, structures with deviation from ideal design are studied. The symmetry breakage of the structures and the displacement fields makes the mechanical effective masses reduced and close to 4 fg. The devices can be used in ultrasensitive sensing of mass, force and displacement. PMID- 26368420 TI - Digital linearization of multi-carrier RF link with photonic bandpass sampling. AB - Due to the capacity in simultaneously down-converting and receiving ultra wideband, multi-carrier radio frequency (RF) or microwave signals, the photonic bandpass sampling has found more and more applications in multi-carrier communication, frequency-agile coherent radar, compressive sensing, etc. The nonlinear transfer during the electronics-to-optics conversion results in distortions, which are bandpass sampled and frequency-folded within the first Nyquist zone, together with the target signals. Because of the multi-octave-span operation, all nonlinearities must be considered besides the usually-concerned third-order inter-modulation distortion (IMD3). We show theoretically that a photonic bandpass sampling link is equivalent to a baseband digital nonlinear link, and then propose a corresponding linearization scheme for the output signal. Such digital linearization is capable of suppressing all types of distortions. Both numerical and experimental examples are demonstrated, where all of the 3rd-order nonlinearities, including the internal and external IMD3, the cross modulation, and 3rd-order harmonics, are well eliminated. PMID- 26368421 TI - Femtosecond laser processing with a holographic line-shaped beam. AB - Line-shaped femtosecond pulses are well-suited to large-area machining with high throughput in laser cutting, peeling, and grooving of materials. First, we demonstrated the single-shot fabrication of a line structure in a glass surface using a line-shaped pulse generated by a holographic cylindrical lens displayed on a liquid-crystal spatial light modulator. We found the line structure was uniform and smooth near the ends because of the ability to precisely control the intensity distribution and to achieve single-shot fabrication. Second, we demonstrated a line-shaped beam deformed three-dimensionally for showing the potential of holographic line-shaped beam processing. Third, we demonstrated laser peeling of an indium tin oxide film. We found that little debris around the fabricated area was observed, because the debris was removed by the beam itself. Last, we demonstrated laser grooving of stainless steel. We found the swelling of the surface included upwardly growing nanogratings, although many line-shaped pulse irradiations were given. The swelling was caused by the depositions of the debris on the top of the nanogratings. PMID- 26368422 TI - Optimal length of ZnO nanorods for improving the light-extraction efficiency of blue InGaN light-emitting diodes. AB - Optimal length of ZnO nanorods (NRs) on blue InGaN light-emitting diodes (LEDs) was investigated to improve the light-extraction efficiency (LEE) of the LED. X ray diffraction, photoluminescence spectroscopy, and micro-Raman spectroscopy were employed to determine the structural and optical properties of the ZnO NRs with length of 300 nm and 5 MUm grown by a hydrothermal method. From the conventional light output power versus injection current (L-I) measurement, we found that the light output power of the LEDs with 300-nm- and 5-MUm-long ZnO NRs was approximately 14.6% and 40.7% greater, respectively, than that of the LED without the ZnO NRs at an operating current of 20 mA. In addition, there were almost no changes to the electrical properties of the ZnO-NR-coated LEDs. The effect of the length of the ZnO NRs on the LEE of the LEDs was theoretically verified with three-dimensional finite-difference time-domain (FDTD) analysis. The FDTD images of the optical power and far-field radiation patterns of the LEDs showed that more photons were guided to the out of the LED by the longer ZnO NRs than by the shorter ZnO NRs grown on the LEDs. PMID- 26368423 TI - CMOS-compatible plenoptic detector for LED lighting applications. AB - LED lighting systems with large color gamuts, with multiple LEDs spanning the visible spectrum, offer the potential of increased lighting efficiency, improved human health and productivity, and visible light communications addressing the explosive growth in wireless communications. The control of this "smart lighting system" requires a silicon-integrated-circuit-compatible, visible, plenoptic (angle and wavelength) detector. A detector element, based on an offset-grating coupled dielectric waveguide structure and a silicon photodetector, is demonstrated with an angular resolution of less than 1 degrees and a wavelength resolution of less than 5 nm. PMID- 26368424 TI - Micro-anatomical and functional assessment of ciliated epithelium in mouse trachea using optical coherence phase microscopy. AB - Motile cilia perform a range of important mechanosensory and chemosensory functions, along with expulsion of mucus and inhaled pathogens from the lungs. Here we demonstrate that spectral domain optical coherence phase microscopy (SD OCPM), which combines the principles of optical coherence tomography (OCT) and confocal microscopy, is particularly well-suited for characterization of both morphology and the ciliary dynamics of mouse trachea. We present micro-anatomical images of mouse trachea, where different cell types can be clearly visualized. The phase contrast, which measures the sub-nanometer changes in axial optical pathlength is used to determine the frequency and direction of cilia beatings. PMID- 26368425 TI - Software reconfigurable highly flexible gain switched optical frequency comb source. AB - The authors present the performance and noise properties of a software reconfigurable, FSR and wavelength tunable gain switched optical frequency comb source. This source, based on the external injection of a temperature tuned Fabry Perot laser diode, offers quasi-continuous wavelength tunability over the C-band (30nm) and FSR tunability ranging from 6 to 14GHz. The results achieved demonstrate the excellent spectral quality of the comb tones (RIN ~-130dB/Hz and low phase noise of 300kHz) and its outstanding stability (with fluctuations of the individual comb tones of less than 0.5dB in power and 5pm in wavelength, characterized over 24hours) highlighting its suitability for employment in next generation flexible optical transmission networks. PMID- 26368426 TI - Vicarious calibration of the Geostationary Ocean Color Imager. AB - Measurements of ocean color from Geostationary Ocean Color Imager (GOCI) with a moderate spatial resolution and a high temporal frequency demonstrate high value for a number of oceanographic applications. This study aims to propose and evaluate the calibration of GOCI as needed to achieve the level of radiometric accuracy desired for ocean color studies. Previous studies reported that the GOCI retrievals of normalized water-leaving radiances (nLw) are biased high for all visible bands due to the lack of vicarious calibration. The vicarious calibration approach described here relies on the assumed constant aerosol characteristics over the open-ocean sites to accurately estimate atmospheric radiances for the two near-infrared (NIR) bands. The vicarious calibration of visible bands is performed using in situ nLw measurements and the satellite-estimated atmospheric radiance using two NIR bands over the case-1 waters. Prior to this analysis, the in situ nLw spectra in the NIR are corrected by the spectrum optimization technique based on the NIR similarity spectrum assumption. The vicarious calibration gain factors derived for all GOCI bands (except 865nm) significantly improve agreement in retrieved remote-sensing reflectance (Rrs) relative to in situ measurements. These gain factors are independent of angular geometry and possible temporal variability. To further increase the confidence in the calibration gain factors, a large data set from shipboard measurements and AERONET-OC is used in the validation process. It is shown that the absolute percentage difference of the atmospheric correction results from the vicariously calibrated GOCI system is reduced by ~6.8%. PMID- 26368427 TI - Effects of haze particles and fog droplets on NLOS ultraviolet communication channels. AB - The performance of non-line-of-sight ultraviolet (UV) scattering communication depends largely on atmospheric parameters. In this paper, we consider haze, fog, two common types of aerosols, and introduce the density and size of aerosols as variables to study the channel path loss for the UV scattering communications. We modify a Monte-Carlo based multiple-scattering model and provide fitting functions to replace the complex calculations of Mie theory, which can be used to obtain the atmospheric coefficients and phase functions for the aerosols. Simulation results reveal that, given fixed elevation angles, the channel path loss is related to both communication range, the aerosol density, and size of aerosols. For a short communication range, an increase of aerosol density can reduce the path loss, which improves the performance of UV scattering communication. However, when the communication range is extended, the path loss will fall first and then rise with density of aerosols. This phenomenon also occurs for an increase of fog drop size. The density or size of aerosols that has the lowest path loss is inversely proportional to the communication range. PMID- 26368428 TI - Ultra-wideband surface plasmonic Y-splitter. AB - We present an ultra-wideband Y-splitter based on planar THz plasmonic metamaterials, which consists of a straight waveguide with composite H-shaped structure and two branch waveguides with H-shaped structure. The spoof surface plasmonic polaritons (SSPPs) supported by the straight waveguide occupy the similar dispersion relation and mode characteristic to the ones confined by the branch waveguides. Attributing to these features, the two branch waveguides can equally separate the SSPPs wave propagating along the straight plasmonic waveguide to form a 3dB power divider in an ultra-wideband frequency range. To verify the functionality and performance of the proposed Y-splitter, we scaled down the working frequency to microwave and implemented microwave experiments. The tested device performances have clearly validated the functionality of our designs. It is believed to be applicable for future plasmonic circuit in microwave and THz ranges. PMID- 26368429 TI - Independent manipulation of the phase and amplitude of optical sidebands in a highly-stable RF photonic filter. AB - Microwave photonic cancellation notch filters have been shown capable of achieving ultra-high suppressions independently from the strength of optical resonant filter they use, making them an attractive candidate for on-chip signal processing. Their operation, based on destructive interference in the electrical domain, requires precise control of the phase and amplitude of the optical modulation sidebands. To date, this was attainable only through the use of dual parallel Mach-Zehnder modulators which suffer from bias drifts that prevent stable filter operation. Here we propose a new cancellation filter topology with ease of control and enhanced stability using a bias-free phase modulator and a reconfigurable optical processor as the modulation sidebands spectral shaper. We experimentally verify the long term stability of the novel filter topology through continuous real-time monitoring of the filter peak suppression over 24 hours. PMID- 26368430 TI - Temporal mode sorting using dual-stage quantum frequency conversion by asymmetric Bragg scattering. AB - The temporal shape of single photons provides a high-dimensional basis of temporal modes, and can therefore support quantum computing schemes that go beyond the qubit. However, the lack of linear optical components to act as quantum gates has made it challenging to efficiently address specific temporal mode components from an arbitrary superposition. Recent progress towards realizing such a "quantum pulse gate," has been proposed using nonlinear optical signal processing to add coherently the effect of multiple stages of quantum frequency conversion. This scheme, called temporal-mode interferometry [D. V. Reddy, Phys. Rev. A 91, 012323 (2015)], has been shown in the case of three-wave mixing to promise near-unity mode-sorting efficiency. Here we demonstrate that it is also possible to achieve high mode-sorting efficiency using four-wave mixing, if one pump pulse is long and the other short - a configuration we call asymmetrically-pumped Bragg scattering. PMID- 26368431 TI - 4.8 Gbit/s 16-QAM-OFDM transmission based on compact 450-nm laser for underwater wireless optical communication. AB - We experimentally demonstrate an underwater wireless optical communications (UWOC) employing 450-nm TO-9 packaged and fiber-pigtailed laser diode (LD) directly encoded with an orthogonal frequency division multiplexed quadrature amplitude modulation (QAM-OFDM) data. A record data rate of up to 4.8 Gbit/s over 5.4-m transmission distance is achieved. By encoding the full 1.2-GHz bandwidth of the 450-nm LD with a 16-QAM-OFDM data, an error vector magnitude (EVM) of 16.5%, a signal-to-noise ratio (SNR) of 15.63 dB and a bit error rate (BER) of 2.6 * 10(-3), well pass the forward error correction (FEC) criterion, were obtained. PMID- 26368432 TI - Speckle based X-ray wavefront sensing with nanoradian angular sensitivity. AB - X-ray wavefront sensing techniques play an important role in both in situ metrology of X-ray optics and X-ray phase contrast imaging. In this letter, we report an approach to measure wavefront aberrations simply using abrasive paper. The wavefront phase change induced by the sample under test was extracted from the speckle displacement by applying a cross-correlation algorithm to two series of speckle images collected using two one-dimensional scans, whilst scanning the abrasive paper in a transverse direction to the incident X-ray beam. The angular sensitivity of the proposed method is shown to be around 2 nanoradians. The potential of the proposed technique for characterizing X-ray optics and the study of biomedical specimens is demonstrated by imaging representative samples. PMID- 26368433 TI - Generation of 360 ps laser pulse with 3 J energy by stimulated Brillouin scattering with a nonfocusing scheme. AB - A new technique for generating high energy sub-400 picosecond laser pulses is presented in this paper. The temporally super-Gaussian-shaped laser pulses are used as light source. When the forward pump is reflected by the rear window of SBS cell, the frequency component that fulfills Brillouin frequency shift in its sideband spectrum works as a seed and excites SBS, which results in efficient compression of the incident pump pulse. First the pulse compression characteristics of 20th-order super-Gaussian temporally shaped pulses with 5 ns duration are analyzed theoretically. Then experiment is carried out with a narrow band high power Nd:glass laser system at the double-frequency and wavelength of 527 nm which delivers 5 ns super-Gaussian temporally shaped pulses with single pulse energy over 10 J. FC-40 is used as the active SBS medium for its brief phonon lifetime and high power capacity. In the experiment, the results agree well with the numerical calculations. With pump energy of 5.36J, the compression of pulse duration from 5 ns to 360 ps is obtained. The output energy is 3.02 J and the peak-power is magnified 8.3 times. Moreover, the compressed pulse shows a high stability because it is initiated by the feedback of rear window rather than the thermal noise distributing inside the medium. This technique of generating high energy hundred picosecond laser pulses has simple structure and is easy to operate, and it also can be scaled to higher energy pulse compression in the future. Meanwhile, it should also be taken into consideration that in such a nonfocusing scheme, the noise-initiated SBS would increase the distortion on the wavefront of Stokes beam to some extent, and the pump energy should be controlled below the threshold of noise-initiated SBS. PMID- 26368434 TI - Enhanced structural sensitivity of hybrid-mode acoustic phonons in axially varying photonic crystal fiber. AB - We report the observation of anti-crossings between hybrid-mode acoustic phonons in an axially-varying photonic crystal fiber. Our experimental results are analyzed using an electrostriction theory which reveals strong coupling between longitudinal and shear components of elastic wave. These anti-crossings are highly sensitive to the transverse fiber structure and thus could be potentially used for ultra-sensitive sensors and new opto-acoustic devices. PMID- 26368435 TI - Wide-viewing integral imaging using fiber-coupled monocentric lens array. AB - We propose a novel three dimensional integral imaging display system with improved viewing angle using a monocentric lens array (MoLA) coupled with fiber bundle. In conventional integral imaging, the off-axis aberrations of the conventional lens array limit the viewing angle in the display stage. The key to our design is a MoLA that eliminates most of the off-axis aberrations and generates a wide-angle image on a spherical surface. The fiber bundle acts as relay optics from the flat-panel display to spherical focal plane of the MoLA. The viewing angle enhancement of the proposed method is analyzed, and the achromatic condition is deduced for the MoLA to correct the chromatic aberration. The experimental result illustrates the capabilities of the proposed method. PMID- 26368436 TI - Laminated metamaterial flat lens at millimeter-wave frequencies. AB - A flat and thin shape is obviously advantageous not only in terms of reducing the volume of a device, but also in handling and using it. Particularly, laminating or stacking flat devices is an intuitive and straightforward way of tailoring performance and functions. Here, we experimentally demonstrated a laminated flat lens for millimeter-wave frequencies that is based on split-ring resonators (SRRs) composed of multiple layers with different and/or identical index profiles and that exhibits characteristics that are linear combinations of those of the individual lenses. Since the characteristics of the lenses of each layer are preserved regardless of the neighbouring layers, the desired functionalities can be easily implemented simply by laminating elementary lenses designed already. When we laminated two lenses designed for bending or focusing incoming waves at 120 GHz, we clearly observed that the outgoing waves collimated and bended as desired. PMID- 26368437 TI - Analysis of an electro-optic modulator based on a graphene-silicon hybrid 1D photonic crystal nanobeam cavity. AB - We propose and numerically study an on-chip graphene-silicon hybrid electro-optic (EO) modulator operating at the telecommunication band, which is implemented by a compact 1D photonic crystal nanobeam (PCN) cavity coupled to a bus waveguide with a graphene sheet on top. Through electrically tuning the Fermi level of the graphene, both the quality factor and the resonance wavelength can be significantly changed, thus the in-plane lightwave can be efficiently modulated. Based on finite-difference time-domain (FDTD) simulation results, the proposed modulator can provide a large free spectral range (FSR) of 125.6 nm, a high modulation speed of 133 GHz, and a large modulation depth of ~12.5 dB in a small modal volume, promising a high performance EO modulator for wavelength-division multiplexed (WDM) optical communication systems. PMID- 26368438 TI - Computational study of radiation torque on arbitrary shaped particles with MLFMA. AB - The surface integral equation (SIE) method is used for the computational study of radiation torque on arbitrarily shaped homogeneous particles. The Multilevel Fast Multipole Algorithm (MLFMA) is employed to reduce memory requirements and improve the capability of SIE. The resultant matrix equations are solved iteratively to obtain equivalent electric and magnetic currents. Then, radiation torque is computed using the vector flux of the pseudotensor over a spherical surface tightly enclosing the particle. We use, therefore, the analytical electromagnetic field expression for incident waves in the near region, instead of the far-field approximation. This avoids the error which may be caused when describing the incident beam. The numerical results of three kinds of non-spherical particles are presented to illustrate the validity and capability of the developed method. It is shown that our method can be applied to predict, in the rigorous sense, the torque from a beam of any shape on a particle of complex configuration with a size parameter as large as 650. The radiation torques on large ellipsoids are exemplified to show the performance of the method and to study the influence that different aspect ratios have on the results. Then, the code is used for the calculation of radiation torque on objects of complex shape including a biconcave cell-like particle and a motor with a non-smooth surface. PMID- 26368439 TI - Reducing thermal crosstalk in ten-channel tunable slotted-laser arrays. AB - Given the tight constraints on the wavelength stability of sources in optical networks, the thermal crosstalk between operating devices in a ten-channel thermally-tunable slotted laser array for DWDM applications has been investigated. It was found experimentally the current standard thermal solution with the laser array chip mounted on an AlN carrier does not allow for wavelength stability of +/- 25 GHz ( +/- 2 K) with a temperature rise of 5 K measured in a device with 100 mA (CW) applied to a neighbouring laser (device spacing = 360 um). A combined experimental/numerical approach revealed solid state submounts comprising diamond or highly ordered pyrolytic graphite are inadequate to reduce crosstalk below an allowable level. Numerical simulations of advanced cooling technologies reveal a microfluidic enabled substrate would reduce thermal crosstalk between operational devices on the chip to acceptable levels. Critically our simulations show this reduced crosstalk is not at the expense of device tunability as the thermal resistance of individual lasers remains similar for the base and microfluidic cases. PMID- 26368440 TI - Radially and azimuthally polarized laser induced shape transformation of embedded metallic nanoparticles in glass. AB - Radially and azimuthally polarized picosecond (~10 ps) pulsed laser irradiation at 532 nm wavelength led to the permanent reshaping of spherical silver nanoparticles (~30 - 40 nm in diameter) embedded in a thin layer of soda-lime glass. The observed peculiar shape modifications consist of a number of different orientations of nano-ellipsoids in the cross-section of each written line by laser. A Second Harmonic Generation cross-sectional scan method from silver nanoparticles in transmission geometry was adopted for characterization of the samples after laser modification. The presented approach may lead to sophisticated marking of information in metal-glass nanocomposites. PMID- 26368441 TI - Noncritical phase matching fourth harmonic generation properties of KD(2)PO(4) crystals. AB - Noncritical phase matching (NCPM) fourth-harmonic-generation (FHG) experiments were conducted on different deuterium content DKDP crystals by adjusting crystal temperature to generate 266 nm deep UV laser. Specially, near room temperature NCPM is realized in extremely high deuterium content DKDP crystal at 38.6 degrees C, which is the lowest temperature to the best of our knowledge. NCPM temperature of DKDP crystals in 60-100% deuterium content range and 1050-1070 nm wavelength range are determined by a linear relationship according to the experimental and calculated results. Angular tuning properties are independent with deuterium content in medium and higher deuterium content DKDP crystals. All of these results will provide good references for future FHG applications of 1 MUm laser with DKDP crystals. PMID- 26368442 TI - One-shot phase stepping with a pulsed laser and modulation of polarization: application to speckle interferometry. AB - For applications involving time varying optical phase distributions, fast cameras and/or pulsed lasers have to be used. To apply phase-shifting interferometry techniques (PSI) as well, single shot capture is required. Among others, modulation of polarization and phase grating interferometry is a possible technique to be considered. In this paper, a report about the use of this technique based on a double pulse laser system is presented. Single-pulse and twin-pulse operations are considered both in optical interferometers as well as in ESPI systems (mainly in subtraction mode). In ESPI a reduction of the degree of polarization appears due to scattering, so some measures have to be taken to prevent such deletereous effect. To show the feasibility of the proposed variants some experimental results are presented. PMID- 26368443 TI - Concurrent spatial and spectral filtering by resonant nanogratings. AB - Optical devices incorporating resonant periodic layers constitute an emerging technological area. Recent advances include spectral filters, broadband mirrors, and polarizers. Here, we demonstrate concurrent spatial and spectral filtering as a new outstanding attribute of this device class. This functionality is enabled by a unique, near-complete, reflection state that is discrete in both angular and spectral domains and realized with carefully-crafted nanogratings operating in the non-subwavelength regime. We study the pathway and inter-modal interference effects inducing this intriguing reflection state. In a proof-of-concept experiment, we obtain angular and spectral bandwidths of ~4 mrad and ~1 nm, respectively. This filter concept can be used for focus-free spectral and spatial filtering in compact holographic and interferometric optical instruments. PMID- 26368444 TI - Modeling of in vivo acousto-optic two-photon imaging of the retina in the human eye. AB - Our aim is to establish a novel combined acousto-optical method for in vivo imaging of the human retina with the two-photon microscope. In this paper we present modeling results based on eye model samples constructed with parameters measured on patients. We used effectively the potential of the electronic compensation offered by the acousto-optic lenses to avoid the use of adaptive optical correction. Simulation predicted lateral resolution between 1.6 um and 3 um on the retina. This technology allows the visualization of single cells and promises real time measuring of neural activity in individual neurons, neural segments and cell assemblies with 30-100 us temporal and subcellular spatial resolution. PMID- 26368445 TI - Optical pulse shaping based on discrete space-to-time mapping in cascaded co directional couplers. AB - We propose and numerically validate a new design concept for on-chip optical pulse shaping based on discrete space-to-time mapping in cascaded co-directional couplers. We show that under weak-coupling conditions, the amplitude and phase of the discrete complex apodization profile of the device can be directly mapped into its temporal impulse response. In this scheme, the amplitude and phase of the apodization profile can be controlled by tuning the coupling strength and relative time delay between the couplers, respectively. The proposed concept enables direct synthesis of the target temporal waveforms over a very broad range of time-resolution, from the femtosecond to the sub-nanosecond regime, using readily feasible integrated waveguide technologies. Moreover, the device offers compactness and the potential for reconfigurability. PMID- 26368446 TI - Effect of beam hardening on a visibility-contrast image obtained by X-ray grating interferometry. AB - X-ray grating interferometry has been highlighted in the last decade as a multi modal X-ray phase-imaging technique for providing absorption, differential phase, and visibility-contrast images. It has been mainly reported that the visibility contrast in the visibility-contrast image originates from unresolvable random microstructures. In this paper, we show that the visibility contrast is even reduced by a uniform sample with flat surfaces due to the so-called "beam hardening effect", which has to be taken into account when X-rays with a continuous spectrum is used. We drive a criterion for determining whether the beam-hardening effect occurs or not, and propose a method for correcting the effect of beam hardening on a visibility-contrast image. PMID- 26368447 TI - Fabrication and characterization of multimaterial chalcogenide glass fiber tapers with high numerical apertures. AB - This paper reports on the fabrication and characterization of multimaterial chalcogenide fiber tapers that have high numerical apertures (NAs). We first fabricated multimaterial As(2)Se(3)-As(2)S(3) chalcogenide fiber preforms via a modified one-step coextrusion process. The preforms were drawn into multi- and single-mode fibers with high NAs (~1.45), whose core/cladding diameters were 103/207 and 11/246 MUm, respectively. The outer diameter of the fiber was tapered from a few hundred microns to approximately two microns through a self-developed automatic tapering process. Simulation results showed that the zero-dispersion wavelengths (ZDWs) of the tapers were shorter than 2 MUm, indicating that the tapers can be conveniently pumped by commercial short wavelength infrared lasers. We also experimentally demonstrated the supercontinuum generation (SCG) in a 15 cm-long multimaterial As(2)Se(3)-As(2)S(3) chalcogenide taper with 1.9 MUm core diameter and the ZDW was shifted to 3.3 MUm. When pumping the taper with 100 fs short pulses at 3.4 um, a 20 dB spectral of the generated supercontinuum spans from 1.5 MUm to longer than 4.8 MUm. PMID- 26368448 TI - Fiber-tip gas pressure sensor based on dual capillaries. AB - A micro-cavity fiber Fabry-Perot interferometer based on dual capillaries is proposed and demonstrated for gas pressure measurement. Such a device is fabricated by fusion splicing of a tiny segment of a main-capillary with a feeding-capillary on one end, and a single mode fiber on the other, to allow gas enters the main-capillary via the feeding-capillary. The reflection spectrum of the interferometer device shifts with the variation of gas pressure due to the dependence of gas refractive index on the pressure applied. During the device fabrication process, a core-offset fusion splicing method is adopted, which turns out to be highly effective for reducing the detection limit of the sensor. The experimental results obtained show that the proposed device exhibits a high gas pressure sensitivity of 4147 pm/MPa, a low temperature cross-sensitivity of less than 0.3 KPa/ degrees C at atmospheric pressure, and an excellently low detection limit down to ~4.81 KPa. The robust tip structure, ultra-compact device size and ease of fabrication make the device an attractive candidate for reliable and highly sensitive gas pressure measurement in a precise location. PMID- 26368449 TI - Development and application of a ray-based model of light propagation through a spherical acousto-optic lens. AB - A spherical acousto-optic lens (AOL) consists of four acousto-optic deflectors (AODs) that can rapidly and precisely control the focal position of an optical beam in 3D space. Development and application of AOLs has increased the speed at which 3D random access point measurements can be performed with a two-photon microscope. This has been particularly useful for measuring brain activity with fluorescent reporter dyes because neuronal signalling is rapid and sparsely distributed in 3D space. However, a theoretical description of light propagation through AOLs has lagged behind their development, resulting in only a handful of simplified principles to guide AOL design and optimization. To address this we have developed a ray-based computer model of an AOL incorporating acousto-optic diffraction and refraction by anisotropic media. We extended an existing model of a single AOD with constant drive frequency to model a spherical AOL: four AODs in series driven with linear chirps. AOL model predictions of the relationship between optical transmission efficiency and acoustic drive frequency including second order diffraction effects closely matched experimental measurements from a 3D two-photon AOL microscope. Moreover, exploration of different AOL drive configurations identified a new simple rule for maximizing the field of view of our compact AOL design. By providing a theoretical basis for understanding optical transmission through spherical AOLs, our open source model is likely to be useful for comparing and improving different AOL designs, as well as identifying the acoustic drive configurations that provide the best transmission performance over the 3D focal region. PMID- 26368450 TI - Fast and simple spectral FLIM for biochemical and medical imaging. AB - Spectrally resolved fluorescence lifetime imaging microscopy (lambdaFLIM) has powerful potential for biochemical and medical imaging applications. However, long acquisition times, low spectral resolution and complexity of lambdaFLIM often narrow its use to specialized laboratories. Therefore, we demonstrate here a simple spectral FLIM based on a solid-state detector array providing in-pixel histrogramming and delivering faster acquisition, larger dynamic range, and higher spectral elements than state-of-the-art lambdaFLIM. We successfully apply this novel microscopy system to biochemical and medical imaging demonstrating that solid-state detectors are a key strategic technology to enable complex assays in biomedical laboratories and the clinic. PMID- 26368451 TI - Low V(pi) Silicon photonics modulators with highly linear epitaxially grown phase shifters. AB - We report on the design of Silicon Mach-Zehnder carrier depletion modulators relying on epitaxially grown vertical junction diodes. Unprecedented spatial control over doping profiles resulting from combining local ion implantation with epitaxial overgrowth enables highly linear phase shifters with high modulation efficiency and comparatively low insertion losses. A high average phase shifter efficiency of VpiL = 0.74 V?cm is reached between 0 V and 2 V reverse bias, while maintaining optical losses at 4.2 dB/mm and the intrinsic RC cutoff frequency at 48 GHz (both at 1 V reverse bias). The fabrication process, the sensitivity to fabrication tolerances, the phase shifter performance and examples of lumped element and travelling wave modulators are modeled in detail. Device linearity is shown to be sufficient to support complex modulation formats such as 16-QAM. PMID- 26368452 TI - Topology optimized all-dielectric cloak: design, performances and modal picture of the invisibility effect. AB - We present the design of an all-dielectric cloaking device at microwave frequencies. A gradient based topology optimization is employed to find a dielectric permittivity distribution that minimizes the diffracted field in free space. The layout is binary, i.e. made either of standard ABS plastic or air and is designed to reduce the scattering from an ABS cylinder excited by a line source for TE polarization. We study the performances of cloaks optimized for one, two and three frequencies in terms of scattering reduction and correlations with respect to the free space propagation case. Finally, a modal analysis is carried out providing physical insights on the resonant cloaking mechanism at stake. PMID- 26368453 TI - Modified sequential algorithm for the on-line characterization of optical coatings. AB - We present a new algorithm for the on-line determination of thicknesses of deposited layers that can be used in the course of coating production with broadband optical monitoring. The proposed algorithm can be considered as a modification of the well-known sequential algorithm. The main idea of the new algorithm is to re-calculate thicknesses of some of the previously deposited layers along with the determination of the thickness of the last deposited layer. The algorithm implies analytical estimations that enable recalculating only those layer thicknesses that can be found with better accuracy than before. Simulation and computational manufacturing experiments confirm high accuracy of the proposed algorithm. PMID- 26368454 TI - Long-period gratings inscribed in photonic crystal fiber by symmetric CO(2) laser irradiation: erratum. AB - This erratum amends the wrongly cited NSF grant number in acknowledgment section in our publication. PMID- 26368455 TI - Three-dimensional cooling of a single atom by a pair of counter-propagating tightly focused beams. AB - A light beam tightly focused by a high numerical-aperture lens system contains longitudinal components with polarization parallel to the propagation axis. By numerically analyzing the polarization distribution around the focal region in one pair of confocally aligned counter-propagating tightly focused light beams with orthogonal linear polarizations, we found that there exists a three dimensional polarization gradient pattern similar to that used in cooling neutral atoms. This can be used to three-dimensionally cool atoms trapped in a far-off resonant trap with only one pair of counter-propagating beams in one dimension. This new cooling scheme can be used to individually cool single atoms in an addressable two-dimensional single-atom array for quantum information processing and be applied to perform readouts of qubit encoded in these atoms without losing them. PMID- 26368456 TI - Contribution of Raman scattering to polarized radiation field in ocean waters. AB - We have implemented Raman scattering in a vector radiative transfer model for coupled atmosphere and ocean systems. A sensitivity study shows that the Raman scattering contribution is greatest in clear waters and at longer wavelengths. The Raman scattering contribution may surpass the elastic scattering contribution by several orders of magnitude at depth. The degree of linear polarization in water is smaller when Raman scattering is included. The orientation of the polarization ellipse shows similar patterns for both elastic and inelastic scattering contributions. As polarimeters and multipolarization-state lidars are planned for future Earth observing missions, our model can serve as a valuable tool for the simulation and interpretation of these planned observations. PMID- 26368457 TI - Spectral amplitude and phase noise characterization of titanium-sapphire lasers. AB - There are few methods capable of characterizing pulse-to-pulse noise in high repetition rate ultrafast lasers. Here we use a recently developed method, termed fidelity, to determine the spectral amplitude and phase noise that leads to lack of pulse repeatability and degrades the performance of laser sources. We present results for a titanium sapphire oscillator and a regenerative amplifier system under different noise conditions. Our experimental results are backed by numerical calculations. PMID- 26368458 TI - Polarimetric target detection under uneven illumination. AB - In polarimetric imaging, the uneven illumination could cause the significant spatial intensity fluctuations in the scene, and thus hampers the target detection. In this paper, we propose a method of illumination compensation and contrast optimization for Stokes polarimetric imaging, which allows significantly increasing the performance of target detection under uneven illumination. We show with numerical simulation and real-world experiment that, based on the intensity information contained in the polarization information, the contrast can be effectively enhanced by proper approach, which is of particular importance in practical applications with spatial illumination fluctuations, such as remote sensing. PMID- 26368459 TI - Long-distance super-resolution imaging assisted by enhanced spatial Fourier transform. AB - A new gradient-index (GRIN) lens that can realize enhanced spatial Fourier transform (FT) over optically long distances is demonstrated. By using an anisotropic GRIN metamaterial with hyperbolic dispersion, evanescent wave in free space can be transformed into propagating wave in the metamaterial and then focused outside due to negative-refraction. Both the results based on the ray tracing and the finite element simulation show that the spatial frequency bandwidth of the spatial FT can be extended to 2.7k(0) (k(0) is the wave vector in free space). Furthermore, assisted by the enhanced spatial FT, a new long distance (in the optical far-field region) super-resolution imaging scheme is also proposed and the super resolved capability of lambda/5 (lambda is the wavelength in free space) is verified. The work may provide technical support for designing new-type high-speed microscopes with long working distances. PMID- 26368460 TI - Reactive molten core fabrication of glass-clad Se(0.8)Te(0.2) semiconductor core optical fibers. AB - Phosphate glass-clad optical fibers comprising amorphous Se(0.8)Te(0.2) semiconductor core were fabricated by a reactive molten core approach. The Se(0.8)Te(0.2) crystals were precipitated in core region by a postdrawing annealing process, which were confirmed by X-ray diffraction, micro-Raman spectra, electron probe X-ray micro-analyzer, and transmission electron microscope measurement results. A two-cm-long crystalline Se(0.8)Te(0.2) semiconductor core optical fiber, electrically contacted to external circuitry through the fiber end facets, exhibits a two-orders-of-magnitude change in conductivity between dark and illuminated states. The great discrepancy in light and dark conductivity suggests that such crystalline Se(0.8)Te(0.2) semiconductor core optical fibers have promising applications in optical switch and photoconductivity of optical fiber array. PMID- 26368461 TI - Identification of surface defects on glass by parallel spectral domain optical coherence tomography. AB - Defects can dramatically degrade glass quality, and automatic inspection is a trend of quality control in modern industry. One challenge in inspection in an uncontrolled environment is the misjudgment of fake defects (such as dust particles) as surface defects. Fortunately, optical changes within the periphery of a surface defect are usually introduced while those of a fake defect are not. The existence of changes within the defect peripheries can be adopted as a criterion for defect identification. However, modifications within defect peripheries can be too small to be noticeable in intensity based optical image of the glass surface, and misjudgments of modifications may occur due to the incorrectness in defect demarcation. Thus, a sensitive and reliable method for surface defect identification is demanded. To this end, a nondestructive method based on optical coherence tomography (OCT) is proposed to precisely demarcate surface defects and sensitively measure surface deformations. Suspected surface defects are demarcated using the algorithm based on complex difference from expectation. Modifications within peripheries of suspected surface defects are mapped by phase information from complex interface signal. In this way, surface defects are discriminated from fake defects using a parallel spectral domain OCT (SD-OCT) system. Both simulations and experiments are conducted, and these preliminary results demonstrate the advantage of the proposed method to identify glass surface defects. PMID- 26368462 TI - Localized surface plasmon enhanced emission of organic light emitting diode coupled to DBR-cathode microcavity by using silver nanoclusters. AB - In this work, we aim to increase the emission of the standard guest-host organic light emitting diode (OLED) thanks to localized surface plasmon and to investigate this effect in a microcavity. As a first step, we consider thermal deposition of silver clusters within an OLED guest-host stack. We investigate both the influence of the size of silver nanoparticles (Ag-NPs) and their position within the OLED heterostructure. Secondly, we study the optimized OLED within a microcavity formed by Al-cathode top mirror and a Distributed Bragg Reflector (DBR) bottom mirror. The experimental results show a substantial enhancement of the electroluminescence (EL) intensity as well as a reduction of the spectral width at a half maximum. PMID- 26368463 TI - Mode-selective optical packet switching in mode-division multiplexing networks. AB - A novel mode-selective optical packet switching, based on mode multiplexers/demultiplexers and multi-port optical micro-electro-mechanical systems (MEMS) switches, has been proposed and experimentally demonstrated. The experimental demonstration was performed using the LP(01), LP(11a) and LP(11b) modes of a 30-km long mode-division multiplexed few-mode fiber link, utilizing 40 Gb/s, 16-QAM signals. PMID- 26368464 TI - Super resolved optical system for objects with finite sizes using circular gratings. AB - We present a real time all optical super resolution method for exceeding the diffraction limit of an imaging system which has a circular aperture. The resolution improvement is obtained using two fixed circular gratings which are placed in predetermined positions. The circular gratings generate synthetic circular duplications of the aperture, thus they are the proper choice for a circular aperture optical system. The method is applicable for both spatially coherent and incoherent illuminations, as well as for white light illumination. The resolution improvement is achieved by limiting the object field of view. The proposed method is presented analytically, demonstrated via numerical simulations, and validated by laboratory experiments. PMID- 26368465 TI - Realizing Rec. 2020 color gamut with quantum dot displays. AB - We analyze how to realize Rec. 2020 wide color gamut with quantum dots. For photoluminescence, our simulation indicates that we are able to achieve over 97% of the Rec. 2020 standard with quantum dots by optimizing the emission spectra and redesigning the color filters. For electroluminescence, by optimizing the emission spectra of quantum dots is adequate to render over 97% of the Rec. 2020 standard. We also analyze the efficiency and angular performance of these devices, and then compare results with LCDs using green and red phosphors-based LED backlight. Our results indicate that quantum dot display is an outstanding candidate for achieving wide color gamut and high optical efficiency. PMID- 26368466 TI - Signal-signal beat interference cancellation in spectrally-efficient WDM direct detection Nyquist-pulse-shaped 16-QAM subcarrier modulation. AB - An experimental demonstration of direct-detection single-sideband Nyquist-pulse shaped 16-QAM subcarrier modulated (Nyquist-SCM) transmission implementing a receiver-based signal-signal beat interference (SSBI) cancellation technique is described. The performance improvement with SSBI mitigation, which compensates for the nonlinear distortion caused by square-law detection, was quantified by simulations and experiments for a 7 * 25 Gb/s WDM Nyquist-SCM signal with a net optical information spectral density (ISD) of 2.0 (b/s)/Hz. A reduction of 3.6 dB in the back-to-back required OSNR at the HD-FEC threshold was achieved. The resulting reductions in BER in single channel and WDM transmission over distances of up to 800 km of uncompensated standard single-mode fiber (SSMF) achieved are presented. PMID- 26368467 TI - Simulating binocular vision for no-reference 3D visual quality measurement. AB - Perceptual quality measurement of three-dimensional (3D) visual signals has become a fundamental challenge in 3D imaging fields. This paper proposes a novel no-reference (NR) 3D visual quality measurement (VQM) metric that uses simulations of the primary visual cortex (V1) of binocular vision. As the major technical contribution of this study, perceptual properties of simple and complex cells are considered for NR 3D-VQM. More specifically, the metric simulates the receptive fields of simple cells (one class of V1 neurons) using Gaussian derivative functions, and the receptive fields of complex cells (the other class of V1 neurons) using disparity energy responses and binocular rivalry responses. Subsequently, various quality-aware features are extracted from the primary visual cortex; these will change in the presence of distortions. Finally, those features are mapped to the subjective quality score of the distorted 3D visual signal by using support vector regression (SVR). Experiments on two publicly available 3D databases confirm the effectiveness of our proposed metric, compared to the relevant full-reference (FR) and NR metrics. PMID- 26368468 TI - Quantitative phase imaging in flows with high resolution holographic diffraction grating. AB - This paper proposes quantitative phase imaging by using a high resolution holographic grating for generating a four-wave shearing interferogram. The high resolution holographic grating is designed in a "kite" configuration so as to avoid parasitic mixing of diffraction orders. The selection of six diffraction orders in the Fourier spectrum of the interferogram allows reconstructing phase gradients along specific directions. The spectral analysis yields the useful parameters of the reconstruction process. The derivative axes are exactly determined whatever the experimental configurations of the holographic grating. The integration of the derivative yields the phase and the optical thickness. Demonstration of the proposed approach is carried out for the case of the analysis of the supersonic flow of a small vertical jet, 5.56mm in diameter. The experimental results compared with those obtained with digital holography exhibit a very good agreement. PMID- 26368469 TI - Roughness reduction of large-area high-quality thick Al films for echelle gratings by multi-step deposition method. AB - Generally, echelle grating ruling is performed on a thick Al film. Consequently, high-quality large-area thick Al films preparation becomes one of the most important factors to realize a high-performance large-size echelle grating. In this paper, we propose a novel multi-step deposition process to improve thick Al films quality. Compared with the traditional single-step deposition process, it is found that the multi-step deposition process can effectively suppress large size grains growth resulting in a low surface roughness and high internal compactness of thick Al films. The differences between single- and multi-step deposition processes are discussed in detail. By using multi-step deposition process, we prepared high-quality large-area Al films with a thickness more than 10 MUm on a 520 mm * 420 mm neoceramic glass substrate. PMID- 26368470 TI - Deconvolution of fluorescence lifetime imaging microscopy by a library of exponentials. AB - Fluorescence lifetime microscopy imaging (FLIM) is an optic technique that allows a quantitative characterization of the fluorescent components of a sample. However, for an accurate interpretation of FLIM, an initial processing step is required to deconvolve the instrument response of the system from the measured fluorescence decays. In this paper, we present a novel strategy for the deconvolution of FLIM data based on a library of exponentials. Our approach searches for the scaling coefficients of the library by non-negative least squares approximations plus Thikonov/l(2) or l(1) regularization terms. The parameters of the library are given by the lower and upper bounds in the characteristic lifetimes of the exponential functions and the size of the library, where we observe that this last variable is not a limiting factor in the resulting fitting accuracy. We compare our proposal to nonlinear least squares and global non-linear least squares estimations with a multi-exponential model, and also to constrained Laguerre-base expansions, where we visualize an advantage of our proposal based on Thikonov/l(2) regularization in terms of estimation accuracy, computational time, and tuning strategy. Our validation strategy considers synthetic datasets subject to both shot and Gaussian noise and samples with different lifetime maps, and experimental FLIM data of ex-vivo atherosclerotic plaques and human breast cancer cells. PMID- 26368471 TI - 70 kHz full 4x4 Mueller polarimeter and simultaneous fiber calibration for endoscopic applications. AB - A new set-up is proposed to measure the full polarimetric properties of a sample through an optical fiber, paving the way to full-Mueller endoscopic imaging. The technique combines a channeled spectrum polarimeter and an interferometer. This permits high-speed measurement of two Mueller matrices simultaneously. The first matrix characterizes only the fiber while the second characterizes both fiber and sample. The instrument is validated on vacuum, a quarter-wave plate and a linear polarizer for single-point measurements. Insensitivity of the polarimetric measurement to fiber disturbances is proven while manipulating the fiber. PMID- 26368472 TI - Enhanced transmission modulation based on dielectric metasurfaces loaded with graphene. AB - We present a hybrid graphene/dielectric metasurface design to achieve strong tunable and modulated transmission at near-infrared (near-IR) frequencies. The proposed device is constituted by periodic pairs of asymmetric silicon nanobars placed over a silica substrate. An one-atom-thick graphene sheet is positioned over the all-dielectric metasurface. The in-plane electromagnetic fields are highly localized and enhanced with this metasurface due to its very low Ohmic losses at near-IR wavelengths. They strongly interact with graphene. Sharp Fano type transmission spectrum is obtained at the resonant frequency of this hybrid configuration due to the cancelation of the electric and magnetic dipole responses at this frequency point. The properties of the graphene monolayer flake can be adjusted by tuning its Fermi energy or chemical potential, leading to different doping levels and, equivalently, material parameters. As a result, the Q-factor and the Fano-type resonant transmission spectrum of the proposed hybrid system can be efficiently tuned and controlled due to the strong light-graphene interaction. Higher than 60% modulation in the transmission coefficient is reported at near-IR frequencies. The proposed hybrid graphene/dielectric nanodevice has compact footprint, fast speed, and can be easily integrated to the current CMOS technology. These features would have promising applications to near IR tunable filters, faster optical interconnects, efficient sensors, switches, and amplitude modulators. PMID- 26368473 TI - Fast CNOT gate between two spatially separated atoms via shortcuts to adiabatic passage. AB - Quantum logic gate is indispensable to quantum computation. One of the important qubit operations is the quantum controlled-not (CNOT) gate that performs a NOT operation on a target qubit depending on the state of the control qubit. In this paper we present a scheme to realize the quantum CNOT gate between two spatially separated atoms via shortcuts to adiabatic passage. The influence of various decoherence processes on the fidelity is discussed. The strict numerical simulation results show that the fidelity for the CNOT gate is relatively high. PMID- 26368474 TI - Three dimensional digital holographic aperture synthesis. AB - Aperture synthesis techniques are applied to temporally and spatially diverse digital holograms recorded with a fast focal-plane array. Because the technique fully resolves the downrange dimension using wide-bandwidth FMCW linear-chirp waveforms, extremely high resolution three dimensional (3D) images can be obtained even at very long standoff ranges. This allows excellent 3D image formation even when targets have significant structure or discontinuities, which are typically poorly rendered with multi-baseline synthetic aperture ladar or multi-wavelength holographic aperture ladar approaches. The background for the system is described and system performance is demonstrated through both simulation and experiments. PMID- 26368475 TI - Discerning electromagnetically induced transparency from Autler-Townes splitting in plasmonic waveguide and coupled resonators system. AB - Electromagnetically induced transparency (EIT) and Autler-Townes splitting (ATS) are two phenomena that can affect the transmission of a probe field in the presence of a stronger field, both yielding transparency in the absorption profile. Being able to discriminate these two similar but distinct phenomena is of vital importance. Here we propose a scheme to describe the EIT and ATS phenomena in a plasmonic system. The proposed system consists of one radiative resonator and one subradiant resonator in metal-insulator-metal waveguide, and the transition is observed from the ATS model to the EIT model through three qualitative regions as the coupling strength decreases. In addition, we apply the method proposed by Anisimov to the induced transparency spectrum in our model, and numerically discerning EIT from ATS based on the Akaike's information criterion in a clear way. PMID- 26368476 TI - Conical second harmonic generation in KDP crystal assisted by optical elastic scattering. AB - We observed the generation of phase-matching conical second harmonic generation (SHG) inside KDP crystal under anomalous dispersion condition, which is attributed to complete phase-matching assisted by fundamental wave (FW) and scattering wave. The double-ring pattern of the conical SHG implies that elastic scattering can stimulate two different polarization states of scattering wave. Furthermore, SH ring of KDP displays inhomogeneous intensity around the ring, which has relevance to effective nonlinear coefficient, and it can be used to investigate crystal symmetry. PMID- 26368477 TI - Carrier-envelope phase dependence of molecular harmonic spectral minima induced by mid-infrared laser pulses. AB - The spectral minima in harmonic spectra of H2+ induced by mid-infrared laser pulses are numerically investigated based on two models of Born-Oppenheimer (BO) and non-Born-Oppenheimer (NBO) approximations. The simulation results show that, with the variation of the mid-infrared laser's carrier-envelope phase (CEP), the spectral minima positions (SMPs) are fixed for the BO model, while oscillate periodically for the NBO model. This can be understood by the two-center destructive-interference theory via the detailed investigation to several physical quantities for each CEP case, such as SMPs, effective potential, internuclear separation and the electron's de Broglie wavelength at the time for interference occurring. The fittings to these quantities' CEP-dependent curves demonstrate that they follow a variation law in the form of a sine function. PMID- 26368478 TI - Digital confocal microscopy through a multimode fiber. AB - Acquiring high-contrast optical images deep inside biological tissues is still a challenging problem. Confocal microscopy is an important tool for biomedical imaging since it improves image quality by rejecting background signals. However, it suffers from low sensitivity in deep tissues due to light scattering. Recently, multimode fibers have provided a new paradigm for minimally invasive endoscopic imaging by controlling light propagation through them. Here we introduce a combined imaging technique where confocal images are acquired through a multimode fiber. We achieve this by digitally engineering the excitation wavefront and then applying a virtual digital pinhole on the collected signal. In this way, we are able to acquire images through the fiber with significantly increased contrast. With a fiber of numerical aperture 0.22, we achieve a lateral resolution of 1.5um, and an axial resolution of 12.7um. The point-scanning rate is currently limited by our spatial light modulator (20Hz). PMID- 26368479 TI - Balanced homodyne detection with high common mode rejection ratio based on parameter compensation of two arbitrary photodiodes. AB - A balanced homodyne detector, with a maximum common mode rejection ratio and clearance of 75.2 dB and 37 dB, is experimentally obtained with two arbitrary photodiodes of the same model. On the basis of self-subtraction photodetector scheme, we divide the influence of photodiodes on the common mode rejection ratio into two parts, including magnitude and phase of output signal. The discrepancy of quantum efficiency and dark current affects magnitude of output signal of photodiodes, which is compensated by adjusting the splitter ratio. The difference of the equivalent capacitance and resistance affects the phase of output signal of photodiodes, which is compensated by the differential fine tuning circuit and adjustable bias voltage circuit. With these designs, the developed homodyne detector can be used for measuring accurately the squeezed state. PMID- 26368480 TI - Three-dimensional localized Airy-Laguerre-Gaussian wave packets in free space. AB - We demonstrate three-dimensional (3D) Airy-Laguerre-Gaussian localized wave packets in free space. An exact solution of the (3 + 1)D potential-free Schrodinger equation is obtained by using the method of separation of variables. Linear compressed wave pulses are constructed with the help of a superposition of two counter-accelerating finite energy Airy wave functions and the generalized Laguerre-Gaussian polynomials in cylindrical coordinates. Such wave packets do not accelerate and can retain their structure over several Rayleigh lengths during propagation. The generation, control, and manipulation of the linear but localized wave packets described here is affected by four parameters: the decay factor, the radial mode number, the azimuthal mode number and the modulation depth. PMID- 26368481 TI - Fiber torsion sensor based on a twist taper in polarization-maintaining fiber. AB - A novel optical fiber torsion sensor head is proposed. A section of polarization maintaining fiber (PMF) is spliced between single mode fiber (SMF), and a twist taper is fabricated by a commercial electric-arc fusion splicer in the middle of the PMF. The asymmetric characteristics are obtained by the twist taper so that a fiber torsion sensor with directional discrimination is fabricated. Due to the characteristics of the asymmetric structure, the torsion sensitivity for the twist rate from 0 rad/m to -8 rad/m reaches 2.392 nm/rad.m-1, and for the twist rate from 0 rad/m to 8 rad/m reaches 1.071 nm/rad.m-1 respectively. PMID- 26368482 TI - Real-time adaptive drift correction for super-resolution localization microscopy. AB - Super-resolution localization microscopy involves acquiring thousands of image frames of sparse collections of single molecules in the sample. The long acquisition time makes the imaging setup prone to drift, affecting accuracy and precision. Localization accuracy is generally improved by a posteriori drift correction. However, localization precision lost due to sample drifting out of focus cannot be recovered as the signal is originally detected at a lower peak signal. Here, we demonstrate a method of stabilizing a super-resolution localization microscope in three dimensions for extended periods of time with nanometer precision. Hence, no localization correction after the experiment is required to obtain super-resolved reconstructions. The method incorporates a closed-loop with a feedback signal generated from camera images and actuation on a 3D nanopositioning stage holding the sample. PMID- 26368483 TI - Accurate adjoint design sensitivities for nano metal optics. AB - We present a method for obtaining accurate numerical design sensitivities for metal-optical nanostructures. Adjoint design sensitivity analysis, long used in fluid mechanics and mechanical engineering for both optimization and structural analysis, is beginning to be used for nano-optics design, but it fails for sharp cornered metal structures because the numerical error in electromagnetic simulations of metal structures is highest at sharp corners. These locations feature strong field enhancement and contribute strongly to design sensitivities. By using high-accuracy FEM calculations and rounding sharp features to a finite radius of curvature we obtain highly-accurate design sensitivities for 3D metal devices. To provide a bridge to the existing literature on adjoint methods in other fields, we derive the sensitivity equations for Maxwell's equations in the PDE framework widely used in fluid mechanics. PMID- 26368484 TI - Fluorescence modeling for optimized-binary compressive detection Raman spectroscopy. AB - The recently-developed optimized binary compressive detection (OB-CD) strategy has been shown to be capable of using Raman spectral signatures to rapidly classify and quantify liquid samples and to image solid samples. Here we demonstrate that OB-CD can also be used to quantitatively separate Raman and fluorescence features, and thus facilitate Raman-based chemical analyses in the presence of fluorescence background. More specifically, we describe a general strategy for fitting and suppressing fluorescence background using OB-CD filters trained on third-degree Bernstein polynomials. We present results that demonstrate the utility of this strategy by comparing classification and quantitation results obtained from liquids and powdered mixtures, both with and without fluorescence. Our results demonstrate high-speed Raman-based quantitation in the presence of moderate fluorescence. Moreover, we show that this OB-CD based method is effective in suppressing fluorescence of variable shape, as well as fluorescence that changes during the measurement process, as a result of photobleaching. PMID- 26368485 TI - Phase sensitive parametric fiber amplifier for the 2 MUm wavelength range. AB - A widely tunable phase sensitive parametric fiber amplifier employing a three fiber stages configuration and operating in the 2 MUm wavelength region is demonstrated. Phase sensitive gain levels of 30 dB and a gain variation of 20 dB were measured for a pulsed pump by determining the conversion efficiency near 2 MUm when a signal at 1.281 MUm was applied. The amplifier operates in the wavelength range of 1952 nm to 2098 nm, with its bandwidth being around 0.1 nm. The bandwidth can be controlled by the fiber lengths and their dispersion properties. PMID- 26368486 TI - Multi-Watt femtosecond optical parametric master oscillator power amplifier at 43 MHz. AB - We present a high repetition rate mid-infrared optical parametric master oscillator power amplifier (MOPA) scheme, which is tunable from 1370 to 4120nm. Up to 4.3W average output power are generated at 1370nm, corresponding to a photon conversion efficiency of 78%. Bandwidths of 6 to 12nm with pulse durations between 250 and 400fs have been measured. Strong conversion saturation over the whole signal range is observed, resulting in excellent power stability. The system consists of a fiber-feedback optical parametric oscillator that seeds an optical parametric power amplifier. Both systems are pumped by the same Yb:KGW femtosecond oscillator. PMID- 26368487 TI - Four-wave-mixing-based optical parametric oscillator delivering energetic, tunable, chirped femtosecond pulses for non-linear biomedical applications. AB - A novel concept for an optical parametric oscillator based on four-wave mixing (FOPO) in an optical fiber is presented. This setup has the ability of generating highly chirped signal and idler pulses with compressed pulse durations below 600 fs and pulse energies of up to 250 nJ. At a fixed pump wavelength of 1040 nm, the emerging signal and idler wavelengths can be easily tuned between 867 to 918 nm and 1200 to 1300 nm, respectively, only by altering the cavity length. With compressed peak powers >100 kW and a repetition rate of only 785 kHz, this source provides tunable intense ultra-short pulses at moderate average powers. This setup constitutes a stable, simple and in many ways superior alternative to bulk state-of-the-art OPO light converters for demanding biomedical applications and non-linear microspectroscopy. PMID- 26368488 TI - Laser-induced shift of the Morin point in antiferromagnetic DyFeO(3). AB - Imaging domain structure of antiferromagnetic DyFeO(3) reveals that intense laser excitation can control the temperature of the Morin transition from collinear to non-collinear spin state. Excitation of the antiferromagnet with femtosecond laser pulses with the central wavelength of 800 nm leads to a shift of the transition temperature over 1 K to higher values as if the light effectively cools the irradiated area down. It is suggested that the optical control of the Morin point can be a result of photo-ionization of Dy(3+) ions. PMID- 26368489 TI - Plasmonic random laser on the fiber facet. AB - A random laser on the optical fiber facet is constructed by dipping an optical fiber end face into the solution of polydimethylsiloxane doped with rhodamine 6G organic dye and silver nanowires. The PDMS film doped with rhodamine 6G acts as the active waveguide layer, and the silver nanowires provide a three-dimensional plasmonic feedback. The plasmon resonance of silver nanowires significantly improves the pump efficiency of the random laser. The most output energy of random laser concentrates in a small angle range along the axis of the optical fiber. This fabrication technique provides a simple and efficient way for the fabrication of random lasers on the optical fiber facet with low cost. PMID- 26368490 TI - Non-iterative method for camera calibration. AB - This paper presents a new and effective technique to calibrate a camera without nonlinear iteration optimization. To this end, the centre-of-distortion is accurately estimated firstly. Based on the radial distortion division model, point correspondences between model plane and its image were used to compute the homography and distortion coefficients afterwards. Once the homographies of calibration images are obtained, the camera intrinsic parameters are solved analytically. All the solution techniques applied in this calibration process are non-iterative that do not need any initial guess, with no risk of local minima. Moreover, estimation of the distortion coefficients and intrinsic parameters could be successfully decoupled, yielding the more stable and reliable result. Both simulative and real experiments have been carried out to show that the proposed method is reliable and effective. Without nonlinear iteration optimization, the proposed method is computationally efficient and can be applied to real-time online calibration. PMID- 26368491 TI - Compact distributed fiber SPR sensor based on TDM and WDM technology. AB - By using a twin-core fiber (TCF), we propose and demonstrate a novel distributed SPR sensor, which employs both the time division multiplexing (TDM) technology and the wavelength division multiplexing (WDM) technology together. The proposed sensor has two sensing passages with four sensing channels (and there are two sensing channels in each sensing passage). We employ the TDM technology to realize the two passage distributed sensing, which are parallel-connection; and we employ the WDM technology to realize the distributed sensing of two channels in a sensing passage, which are series-connected. In order to realize the TDM technology, we employ a two-core fiber, which has two cores in a same cladding, being equal to dividing the traditional single core into two independent sensing zones; in order to realize the WDM technology, we employ a fiber end polishing connecting method to adjust the resonance angle/wavelength to realize the dynamic range separation. This twin-passage four-channel twin-core fiber SPR sensor is suitable for applying in fields of the multi-channel liquid refractive index and temperature self-reference measurement. PMID- 26368492 TI - Elimination of image flicker in a fringe-field switching liquid crystal display by applying a bipolar voltage wave. AB - Recently, low-frequency driving of liquid crystal display (LCD) panels to minimize power consumption has drawn much attention. In the case in which an LCD panel is driven by a fringe-field at a low frequency, the image flickering phenomenon occurs when the sign of the applied electric field is reversed. We investigated image flickering induced by the flexoelectric effect in a fringe field switching (FFS) liquid crystal cell in terms of the transmittance difference between frames and the ripple phenomenon. Experimental results show that image flicker due to transmittance difference can be eliminated completely and that the ripple phenomena can be reduced significantly by applying a bipolar voltage wave to the FFS cell. PMID- 26368493 TI - Supercontinuum-based three-color three-pulse time-resolved coherent anti-Stokes Raman scattering. AB - We demonstrate the use of a photonic crystal fiber (PCF) as a compact three-color fs laser system operating at 76 MHz, limited only by the repetition rate of the pump laser. The system is suitable for background-free time-resolved four-wave mixing measurements, which arguably reach fundamental limits in signal detectivity. We give a detailed characterization of the near transform-limited multi-color pulses that are extracted from the PCF, and prove the system through time-resolved coherent anti-Stokes Raman scattering measurements in bipyridyl ethylene and styrene. PMID- 26368494 TI - W-band OFDM photonic vector signal generation employing a single Mach-Zehnder modulator and precoding. AB - We present a simple radio-over-fiber (RoF) link architecture for millimeter-wave orthogonal frequency division multiplexing (OFDM) transmission using only one Mach-Zehnder modulator (MZM) and precoding technique. In the transmission system, the amplitudes and the phase of the driving radio-frequency (RF) OFDM signal on each sub-carrier are precoded, to ensure that the OFDM signal after photodetector (PD) can be restored to original OFDM signal. The experimental results show that the bit-error ratios (BERs) of the transmission system are less than the forward error-correction (FEC) threshold of 3.8 * 10(-3), which demonstrates that the generation of OFDM vector signal based on our proposed scheme can be employed in our system architecture. PMID- 26368495 TI - Breaking the buildup-time limit of sensitivity in avalanche photodiodes by dynamic biasing. AB - Avalanche photodiodes (APDs) are the preferred photodetectors for direct detection, high data-rate long-haul optical telecommunications. APDs can detect low-level optical signals due to their internal amplification of the photon generated electrical current, which is attributable to the avalanche of electron and hole impact ionizations. Despite recent advances in APDs aimed at reducing the average avalanche-buildup time, which causes intersymbol interference and compromises receiver sensitivity at high data rates, operable speeds of commercially available APDs have been limited to 10Gbps. We report the first demonstration of a dynamically biased APD that breaks the traditional sensitivity versus-speed limit by employing a data-synchronous sinusoidal reverse-bias that drastically suppresses the average avalanche-buildup time. Compared with traditional DC biasing, the sensitivity of germanium APDs at 3Gbps is improved by 4.3 dB, which is equivalent to a 3,500-fold reduction in the bit-error rate. The method is APD-type agnostic and it promises to enable operation at rates of 25Gbps and beyond. PMID- 26368496 TI - Broadband infrared spectroscopy using optical parametric oscillation in a radially-poled whispering gallery resonator. AB - We demonstrate optical parametric oscillation in a millimeter-sized whispering gallery resonator suitable for broadband infrared spectroscopy. This nonlinear optical process is quasi-phase-matched using a radial domain pattern with 30 um period length, inscribed by calligraphic poling. The output wavelengths are selected in a controlled way over hundreds of nanometers. We achieve this by increasing the temperature of the resonator in steps such that the azimuthal mode number of the pump wave rises by one. As a proof-of-principle experiment, we measure a characteristic resonance of polystyrene in the spectral range of 2.25 - 2.45 um. PMID- 26368497 TI - Surface lattice solitons in diffusive nonlinear media with spatially modulated nonlinearity. AB - Two families of gap and twisted surface lattice solitons in diffusive nonlinear periodic media with spatially modulated nonlinearity are reported. It is shown that the existence and stability of such solitons are extremely spatially modulated nonlinearity sensitive. For self-focusing nonlinearity, gap surface solitons belonging to the semi-infinite gap are stable in whole existence domain, twisted surface solitons are also linearly stable in low modulated strength region and a very narrow unstable region near the upper cutoff appears in high modulated strength region. In the self-defocusing case, surface gap solitons belonging to the first gap can propagate stably in whole existence domain except for an extremely narrow region close to the Bloch band, twisted solitons belonging to this gap are unstable in the entire existence domain. PMID- 26368498 TI - Gold nanoparticles as a saturable absorber for visible 635 nm Q-switched pulse generation. AB - Gold nanoparticle (GNP) possesses saturable absorption bands in the visible region induced by surface plasmon resonance (SPR). We firstly applied the GNP as a visible saturable absorber (SA) for the red Q-switched pulse generation. The GNPs were embedded in polyvinyl alcohol (PVA) for film-forming and inserted into a praseodymium (Pr(3+))-doped fiber laser cavity to achieve 635 nm passive Q switching. The visible 635 nm Q-switched fiber laser has a wide range of pulse repetition-rate from 285.7 to 546.4 kHz, and a narrow pulse width of 235 ns as well as the maximum output power of 11.1 mW. The results indicate that the GNPs based SA is available for pulsed operation in the visible spectral range. PMID- 26368499 TI - Low-complexity optical phase noise suppression in CO-OFDM system using recursive principal components elimination. AB - A low-complexity optical phase noise suppression approach based on recursive principal components elimination, R-PCE, is proposed and theoretically derived for CO-OFDM systems. Through frequency domain principal components estimation and elimination, signal distortion caused by optical phase noise is mitigated by R PCE. Since matrix inversion and domain transformation are completely avoided, compared with the case of the orthogonal basis expansion algorithm (L = 3) that offers a similar laser linewidth tolerance, the computational complexities of multiple principal components estimation are drastically reduced in the R-PCE by factors of about 7 and 5 for q = 3 and 4, respectively. The feasibility of optical phase noise suppression with the R-PCE and its decision-aided version (DA R-PCE) in the QPSK/16QAM CO-OFDM system are demonstrated by Monte-Carlo simulations, which verify that R-PCE with only a few number of principal components q ( = 3) provides a significantly larger laser linewidth tolerance than conventional algorithms, including the common phase error compensation algorithm and linear interpolation algorithm. Numerical results show that the optimal performance of R-PCE and DA-R-PCE can be achieved with a moderate q, which is beneficial for low-complexity hardware implementation. PMID- 26368500 TI - All-fiberized synchronously pumped 1120 nm picosecond Raman laser with flexible output dynamics. AB - A largely simplified and highly efficient all-fiber-based synchronously pumping scheme is proposed. The synchronization between pump light and the cavity round trip can be achieved by adjusting the repetition rate of pumping light without the requirement of altering the cavity length. Based on this scheme, we achieved generating narrow linewidth highly efficient 1120 nm pulse directly from an all fiber Raman cavity. By pump repetition rate detuning and pump duration adjustment, the duration of the 1120 nm pulse can be widely tuned from 18 ps to ~1 ns, and the repetition rate can be adjusted from 12.41 MHz to 99.28 MHz by harmonic pumping. Up to 4.3 W high power operation is verified based on this scheme. Owing to the compact all-fiber configuration, the conversion efficiency of the 1066 nm pump light to the 1120 nm Stokes light exceeds 80% and the overall conversion efficiency (976 nm-1066 nm-1120 nm) is as high as 53.7%. The nonlinear output dynamics of the Raman laser are comprehensively explored. Two distinct operation regimes are investigated and characterized. PMID- 26368501 TI - Interferometric measurement of the temperature coefficient of the refractive index dn/dT and the coefficient of thermal expansion of Pr:YLF laser crystals: erratum. AB - We present an erratum regarding a few small errors in our manuscript. PMID- 26368502 TI - Tbx16 and Msgn1 are required to establish directional cell migration of zebrafish mesodermal progenitors. AB - The epithelial to mesenchymal transition (EMT) is an essential process that occurs repeatedly during embryogenesis whereby stably adherent cells convert to an actively migrating state. While much is known about the factors and events that initiate the EMT, the steps that cells undergo to become directionally migratory are far less well understood. Zebrafish embryos lacking the transcription factors Tbx16/Spadetail and Mesogenin1 (Msgn1) are a valuable system for investigating the EMT. Mesodermal cells in these embryos are unable to perform the EMT necessary to leave the most posterior end of the body (the tailbud) and join the pre-somitic mesoderm, a process that is conserved in all vertebrates. It has previously been very difficult to study this EMT in vertebrates because of the multiple cell types in the tailbud and the morphogenetic changes the whole embryo undergoes. Here, we describe a novel tissue explant system for imaging the mesodermal cell EMT in vivo that allows us to investigate the requirements for cells to acquire migratory properties during the EMT with high spatio-temporal resolution. This method revealed that, despite the inability of tbx16;msgn1-deficient cells to leave the tailbud, actin-based protrusions form surprisingly normally in these cells and they become highly motile. However, tbx16;msgn1-deficient cells have specific cell-autonomous defects in the persistence and anterior direction of migration because the lamellipodia they form are not productive in driving anteriorward migration. Additionally, we show that mesoderm morphogenesis and differentiation are separable and that there is a migratory cue that directs mesodermal cell migration that is independent of Tbx16 and Msgn1. This work defines changes that cells undergo as they complete the EMT and provides new insight into the mechanisms required in vivo for cells to become mesenchymal. PMID- 26368504 TI - Are There Ethnic Inequalities in Revascularisation Procedure Rate after an ST Elevation Myocardial Infarction? AB - BACKGROUND: Previously, ethnic inequalities in prognosis after a first acute myocardial infarction were observed in the Netherlands. This might be due to differences in revascularisation rate between ethnic minority groups and ethnic Dutch. Therefore, we investigated inequalities in revascularisation rate after occurrence of an ST-elevation myocardial infarction (STEMI) between first generation ethnic minority groups (henceforth, migrants) and ethnic Dutch. METHODS: All STEMI events between 2006 and 2011 were identified in a subset of the Achmea Health Database, which records medical care to persons insured at the Achmea health insurance company, a major health insurance company in the central part of the Netherlands. Ethnic Dutch and migrants from Suriname (Hindustani Surinamese and non-Hindustani Surinamese), Morocco, and Turkey were included (n = 1,765). Multivariable Cox proportional hazards regression analyses were used to identify ethnic inequalities in revascularisation rate (percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG)) after a STEMI event. RESULTS: On average, 73.2% of STEMI events were followed by a revascularisation procedure. After adjustment for confounders (age, sex, degree of urbanization) no significant differences in revascularisation rate were found between the ethnic Dutch population and Hindustani Surinamese (HR: 1.04; 0.85 1.27), non-Hindustani Surinamese (HR: 0.98; 0.63-1.51), Moroccan (HR: 0.94; 0.77 1.14), and Turkish migrants (HR: 1.04; 0.88-1.24). Additional adjustment for comorbidity and neighborhood income did not change our findings. CONCLUSION: Our study suggests no ethnic inequalities in revascularisation rate after a STEMI event. This finding is in agreement with the universally accessible health care system in the Netherlands. PMID- 26368503 TI - Improving the phytoremediation of heavy metals contaminated soil by use of sewage sludge. AB - Sewage sludge, in particular from the food industry, is characterized by fertilizing properties, due to the high content of organic matter and nutrients. The application of sewage sludge causes an improvement of soil parameters as well as increase in cation exchange capacity, and thus stronger binding of cations in the soil environment, which involves the immobilization of nutrients and greater resistance to contamination. In a field experiment sewage sludge has been used as an additive to the soil supporting the phytoremediation process of land contaminated with heavy metals (Cd, Zn, and Pb) using trees species: Scots pine (Pinus silvestris L.), Norway spruce (Picea abies L.), and oak (Quercus robur L.). The aim of the research was to determine how the application of sewage sludge into the soil surface improves the phytoremediation process. The conducted field experiment demonstrated that selected trees like Scots pine and Norway spruce, because of its excellent adaptability, can be used in the remediation of soil. Oak should not be used in the phytoremediation process of soils contaminated with high concentrations of trace elements in the soil, because a significant amount of heavy metals was accumulated in the leaves of oak causing a risk of recontamination. PMID- 26368505 TI - Emergency ultrasound-based algorithms for diagnosing blunt abdominal trauma. AB - BACKGROUND: Ultrasonography (performed by means of a four-quadrant, focused assessment of sonography for trauma (FAST)) is regarded as a key instrument for the initial assessment of patients with suspected blunt abdominal and thoraco abdominal trauma in the emergency department setting. FAST has a high specificity but low sensitivity in detecting and excluding visceral injuries. Proponents of FAST argue that ultrasound-based clinical pathways enhance the speed of primary trauma assessment, reduce the number of unnecessary multi-detector computed tomography (MDCT) scans, and enable quicker triage to surgical and non-surgical care. Given the proven accuracy, increasing availability of, and indication for, MDCT among patients with blunt abdominal and multiple injuries, we aimed to compile the best available evidence of the use of FAST-based assessment compared with other primary trauma assessment protocols. OBJECTIVES: To assess the effects of diagnostic algorithms using ultrasonography including in FAST examinations in the emergency department in relation to the early, late, and overall mortality of patients with suspected blunt abdominal trauma. SEARCH METHODS: The most recent search was run on 30th June 2015. We searched the Cochrane Injuries Group Specialised Register, The Cochrane Library, MEDLINE (OvidSP), EMBASE (OvidSP), ISI Web of Science (SCI-EXPANDED, SSCI, CPCI-S, and CPSI-SSH), clinical trials registers, and screened reference lists. Trial authors were contacted for further information and individual patient data. SELECTION CRITERIA: We included randomised controlled trials (RCTs). Participants were patients with blunt torso, abdominal, or multiple trauma undergoing diagnostic investigations for abdominal organ injury. The intervention was diagnostic algorithms comprising emergency ultrasonography (US). The control was diagnostic algorithms without US examinations (for example, primary computed tomography (CT) or diagnostic peritoneal lavage (DPL)). Outcomes were mortality, use of CT or invasive procedures (DPL, laparoscopy, laparotomy), and cost-effectiveness. DATA COLLECTION AND ANALYSIS: Two authors (DS and CG) independently selected trials for inclusion, assessed methodological quality, and extracted data. Methodological quality was assessed using the Cochrane Collaboration risk of bias tool. Where possible, data were pooled and relative risks (RRs), risk differences (RDs), and weighted mean differences, each with 95% confidence intervals (CIs), were calculated by fixed-effect or random-effects models as appropriate. MAIN RESULTS: We identified four studies meeting our inclusion criteria. Overall, trials were of poor to moderate methodological quality. Few trial authors responded to our written inquiries seeking to resolve controversial issues and to obtain individual patient data. Strong heterogeneity amongst the trials prompted discussion between the review authors as to whether the data should or should not be pooled; we decided in favour of a quantitative synthesis to provide a rough impression about the effect sizes achievable with US-based triage algorithms. We pooled mortality data from three trials involving 1254 patients; the RR in favour of the FAST arm was 1.00 (95% CI 0.50 to 2.00). FAST-based pathways reduced the number of CT scans (random-effects model RD -0.52, 95% CI -0.83 to -0.21), but the meaning of this result was unclear. AUTHORS' CONCLUSIONS: The experimental evidence justifying FAST-based clinical pathways in diagnosing patients with suspected abdominal or multiple blunt trauma remains poor. Because of strong heterogeneity between the trial results, the quantitative information provided by this review may only be used in an exploratory fashion. It is unlikely that FAST will ever be investigated by means of a confirmatory, large-scale RCT in the future. Thus, this Cochrane Review may be regarded as a review which provides the best available evidence for clinical practice guidelines and management recommendations. It can only be concluded from the few head-to-head studies that negative US scans are likely to reduce the incidence of MDCT scans which, given the low sensitivity of FAST (or reliability of negative results), may adversely affect the diagnostic yield of the trauma survey. At best, US has no negative impact on mortality or morbidity. Assuming that major blunt abdominal or multiple trauma is associated with 15% mortality and a CT-based diagnostic work-up is considered the current standard of care, 874, 3495, or 21,838 patients are needed per intervention group to demonstrate non-inferiority of FAST to CT-based algorithms with non-inferiority margins of 5%, 2.5%, and 1%, power of 90%, and a type-I error alpha of 5%. PMID- 26368506 TI - Nanosized LiNi1-xFexPO4 embedded in a mesoporous carbon matrix for high performance electrochemical water splitting. AB - Splitting water to produce oxygen is the key technique in the development of various energy conversion processes including metal-air batteries, fuel cells and water splitting. Herein, for the first time, we report a mesoporous LiNi1 xFexPO4@C (0 <= x <= 1) nano-structure as a highly effective catalyst for electrochemical oxygen evolution reaction (OER) through a spray dry method. In particular, the LiNi1-xFexPO4@C (3 : 1) shows superior activity to those state-of the-art noble metal catalysts (e.g., RuO2 and IrO2), which only needs an overpotential of 311 mV to afford a current density of 10 mA cm(-2) and maintains its high catalytic activity after 1000 cycles. PMID- 26368507 TI - A Paratesticular Serous Borderline Tumor in a Pediatric Patient With Proteus Syndrome. AB - Proteus syndrome is a rare disorder of asymmetric overgrowth of various tissues of the body and is associated with specific tumors appearing before the second decade. Although there have been reports of lesions of the genitourinary tract associated with Proteus syndrome, a case of serous borderline tumor of the paratestis has not been previously recorded. We report the first such case in a 20-month-old child who presented with a left-sided testicular mass that was found on histology to be a serous borderline tumor of the paratestis. Surgical management included a left inguinal radical orchiectomy and surveillance follow up. PMID- 26368508 TI - Review of the Different Treatments and Management for Prostate Cancer and Fertility. AB - OBJECTIVE: To compare the options available for prostate cancer management and their consequences on fertility for men, in order to best advise these men to choose their treatment, especially if they are young, with no child with their current partner. METHODS: A literature review on prostate cancer and fertility over the last 26 years was carried out on PubMed database. The literature was based on evidence and practical considerations. Twenty-nine articles were selected according to their relevance. RESULTS: After prostatectomy, there is an obstructive infertility in 100% of the cases. In external radiotherapy, doses more than 15 cGy induced reduction in sperm count. Direct irradiation between 15 and 35 cGy caused oligozoospermia and doses between 35 and 50 cGy caused reversible azoospermia. The calculated projected doses on testicles were 196 cGy (+/- 145 cGy). The brachytherapy effects on fertility seems to be less harmful. The irradiation dose received by testicles is less important (less than 20 cGy) after brachytherapy than after external radiotherapy. Infertility induced by hormonal therapy alone should be reversible. Fertility and focal therapy have not been well evaluated yet. Active surveillance is the management of prostate cancer which allows to keep at best men's fertility. CONCLUSION: Urologists should consider approaching the topic of infertility when discussing the pros and cons of various prostate cancer management with their younger patients. If a patient with prostate cancer expresses interest in future fertility, a semen analysis should be performed. Cryopreservation represents the only preemptive accompanying possibility to preserve fertility in young cancer patients. PMID- 26368509 TI - Outcomes of Iatrogenic Genitourinary Injuries During Colorectal Surgery. AB - OBJECTIVE: To describe, categorize, and determine the outcomes of repairs of genitourinary (GU) injuries that occur during colorectal surgery. Presently, little is known regarding these injuries or the long-term outcomes of their repair. METHODS: We performed a retrospective review of patients undergoing colorectal surgery between 2003 and 2013 who experienced iatrogenic GU injuries requiring surgical repair. GU repair failures were defined as development of urine leak, urinary fistula, or anastomotic stricture requiring secondary GU intervention. Possible risk factors associated with repair failures were examined and included age, American Society of Anesthesiology score, comorbidities, type of colorectal surgery, radiation, and chemotherapy. RESULTS: Of 42,570 colorectal surgeries performed, 75 GU injuries were identified (0.18%). Mean age was 57.5 years (range, 22-91), and median follow-up was 19.5 months (range, 1-128). Fifty nine (59/75, 79%) patients required a single GU repair whereas 16 of 75 (21%) patients experienced repair failure requiring additional GU intervention. The most common GU injuries were cystotomy (26/75, 35%), incomplete ureteral transection (22/75, 29%), complete proximal and distal ureteral injuries (13/75, 17%; 11/75, 15%), urethral injury (2/75, 3%), and injury to a pre-existing ileal conduit (1/75, 1). Twenty-seven patients (36%) had prior radiation and 35 patients (47%) had prior chemotherapy. Preoperative radiation and chemotherapy were both associated with failure of the GU repair (P = .003; P = .013). Delayed repair of the GU injury was also associated with repair failure (P = .001). CONCLUSION: Iatrogenic GU injuries during colorectal surgery are rare, affecting only 0.18% of colorectal procedures. Preoperative external beam radiation therapy/chemotherapy and delayed GU repair are associated with worse outcomes of repairs of these injuries. PMID- 26368510 TI - Robotic-assisted Laparoscopic Transposition of the Left Renal Vein for Treatment of the Nutcracker Syndrome. AB - Nutcracker syndrome is a rare condition of left renal vein entrapment manifesting with hematuria and flank pain. We report a case of nutcracker syndrome, where a robotic-assisted laparoscopic transposition of the left renal vein was performed. To our knowledge, this is the first case of robotic-assisted laparoscopic surgery of a nutcracker syndrome. PMID- 26368511 TI - Clitoral and labial sizes in women with PCOS. AB - The aim of this study was to examine the external genital features in Turkish women with polycystic ovary syndrome (PCOS). Thirty-two newly diagnosed PCOS cases and 35 healthy women were included the study. All women underwent a thorough gynaecological examination. Clitoral length, and labia minora length and width were recorded. The groups were compared for features of external genital structures. Clitoral and labial lengths were significantly higher in PCOS group. There was a strong correlation between clitoral length and modified Ferriman Gallwey score. The most effective predictor of PCOS was found to be clitoral length. Clitoral length alone predicted 99.9% of PCOS patients. There were some subclinical genital changes in women with PCOS. These changes in PCOS patients may be a sign of hyperandrogenism and might have diagnostic value in indistinct cases. PMID- 26368512 TI - The influence of newborn early literacy intervention programs in three canadian provinces. AB - Low levels of literacy in early childhood can have lasting effects on children's educational and intellectual development. Many countries have implemented newborn literacy programs designed to teach parents pre-literacy promoting activities to share with their children. We conducted 2 quasi-experimental studies using 1) a pre-test/post-test design and 2) a non-equivalent control group design to examine the effect of newborn literacy programs on parents' self-reported literacy intentions/behaviors, values toward literacy, and parent-child interactions. Parents were recruited from 3 provinces, 2 with newborn literacy programs (intervention) and 1 without (control). Parents in the intervention group completed prenatal and postnatal (after participation in program) questionnaires. Parents in the control group completed 1 questionnaire. Questionnaires were designed to capture parents' literacy intentions (prenatal), behaviors (postnatal), values, and parent-child interactions (postnatal). A total of 98 parents were included in study one and 174 were included in study two. Parents' self-reported prenatal intentions and values were higher than their postnatal behaviors and values. Parents in the intervention group exhibited higher literacy behaviors and values and greater enjoyment reading to their children than parents in the control group, though they also reported reading to their children less frequently. Parents in the intervention group had significantly higher Positive Interactive scores than controls. Overall, we found participation in newborn literacy programs positively impacted parenting behaviors and attitudes. Lower postnatal within-group scores (intentions and values versus behaviors and values) may have been the result of participants' high expectations. Given our findings, we recommend that these programs continue. PMID- 26368513 TI - Multilaboratory Comparison of Quantitative PCR Assays for Detection and Quantification of Fusarium virguliforme from Soybean Roots and Soil. AB - The ability to accurately detect and quantify Fusarium virguliforme, the cause of sudden death syndrome (SDS) in soybean, in samples such as plant root tissue and soil is extremely valuable for accurate disease diagnoses and to address research questions. Numerous quantitative real-time polymerase chain reaction (qPCR) assays have been developed for this pathogen but their sensitivity and specificity for F. virguliforme have not been compared. In this study, six qPCR assays were compared in five independent laboratories using the same set of DNA samples from fungi, plants, and soil. Multicopy gene-based assays targeting the ribosomal DNA intergenic spacer (IGS) or the mitochondrial small subunit (mtSSU) showed relatively high sensitivity (limit of detection [LOD] = 0.05 to 5 pg) compared with a single-copy gene (FvTox1)-based assay (LOD = 5 to 50 pg). Specificity varied greatly among assays, with the FvTox1 assay ranking the highest (100%) and two IGS assays being slightly less specific (95 to 96%). Another IGS assay targeting four SDS-causing fusaria showed lower specificity (70%), while the two mtSSU assays were lowest (41 and 47%). An IGS-based assay showed consistently highest sensitivity (LOD = 0.05 pg) and specificity and inclusivity above 94% and, thus, is suggested as the most useful qPCR assay for F. virguliforme diagnosis and quantification. However, specificity was also above 94% in two other assays and their selection for diagnostics and research will depend on objectives, samples, and materials used. These results will facilitate both fundamental and disease management research pertinent to SDS. PMID- 26368514 TI - Towards the Identification of Type III Effectors Associated with Ralstonia solanacearum Virulence on Tomato and Eggplant. AB - For the development of pathogen-informed breeding strategies, identifying the microbial genes involved in interactions with the plant is a critical step. To identify type III effector (T3E) repertoires associated with virulence of the bacterial wilt pathogen Ralstonia solanacearum on Solanaceous crops, we used an original association genetics approach combining DNA microarray data and pathogenicity data on resistant eggplant, pepper, and tomato accessions. From this first screen, 25 T3Es were further full-length polymerase chain reaction amplified within a 35-strain field collection, to assess their distribution and allelic diversity. Six T3E repertoire groups were identified, within which 11 representative strains were chosen to challenge the bacterial wilt-resistant egg plants 'Dingras multiple Purple' and 'AG91-25', and tomato Hawaii 7996. The virulence or avirulence phenotypes could not be explained by specific T3E repertoires, but rather by individual T3E genes. We identified seven highly avirulence-associated genes, among which ripP2, primarily referenced as conferring avirulence to Arabidopsis thaliana. Interestingly, no T3E was associated with avirulence to both egg-plants. Highly virulence-associated genes were also identified: ripA5_2, ripU, and ripV2. This study should be regarded as a first step toward investigating both avirulence and virulence function of the highlighted genes, but also their evolutionary dynamics in natural R. solanacearum populations. PMID- 26368515 TI - Integration Host Factor Is Required for RpoN-Dependent hrpL Gene Expression and Controls Motility by Positively Regulating rsmB sRNA in Erwinia amylovora. AB - Erwinia amylovora requires an hrp-type III secretion system (T3SS) to cause disease. It has been reported that HrpL, the master regulator of T3SS, is transcriptionally regulated by sigma factor 54 (RpoN), YhbH, and HrpS. In this study, the role of integration host factor (IHF) in regulating hrpL and T3SS gene expression was investigated. IHF is a nucleoid-associated protein that regulates gene expression by influencing nucleoid structure and DNA bending. Our results showed that both ihfA and ihfB mutants of E. amylovora did not induce necrotic lesions on pear fruits. Growth of both mutants was greatly reduced, and expression of the hrpL and T3SS genes was significantly down-regulated as compared with those of the wild type. In addition, expression of the ihfA, but not the ihfB gene, was under auto-suppression by IHF. Furthermore, both ihfA and ihfB mutants were hypermotile, due to significantly reduced expression of small RNA (sRNA) rsmB. Electrophoresis mobility shift assay further confirmed that IHF binds to the promoters of the hrpL and ihfA genes, as well as the rsmB sRNA gene. These results indicate that IHF is required for RpoN-dependent hrpL gene expression and virulence, and controls motility by positively regulating the rsmB sRNA in E. amylovora. PMID- 26368516 TI - Some Summary Comments on the Third Colloquium. PMID- 26368517 TI - Contribution of Traffic to PM2.5 Exposure: 30%-or Even Considerably More? PMID- 26368518 TI - Cardiac and Thermoregulatory Toxicity of Residual Oil Fly Ash in Cardiopulmonary Compromised Rats. AB - Recent epidemiological studies have reported a positive association between levels of ambient particulate matter (PM) and daily morbidity and mortality due to respiratory or cardiovascular causes; however, toxicological evidence supporting these findings is limited. The present study compared cardiac and thermoregulatory responses to intratracheal instillations of residual oil fly ash (ROFA) in normal and cardiopulmonary-compromised male Sprague-Dawley rats. Animals (n = 64) were implanted with radiotelemetry transmitters capable of continuously monitoring heart rate, core body temperature, and electrocardiographic waveforms. Comparisons of ROFA toxicity were conducted between (1) healthy rats and rats with cardiopulmonary stress or disease, including (2) rats exposed to an ambient temperature of 10 degrees C, (3) rats preexposed to ozone to induce pulmonary inflammation, and (4) rats pretreated with monocrotaline (MCT) to induce pulmonary hypertension and vasculitis. Animals from each regimen were instilled with 1 of 4 doses of ROFA (0, 0.25, 1.0, 2.5 mg), and telemetry data were acquired for 96 h following ROFA instillation. Dose related hypothermia and bradycardia were observed in healthy animals following exposure to ROFA; the magnitude and duration of these responses were potentiated in all compromised models. Delayed hypothermic and bradycardic responses occurred in healthy animals receiving 2.5 mg ROFA up to 48 h following instillation. These delayed responses were exacerbated in the MCT-and 10 degrees C-exposure models, but attenuated in the 03-preexposed group. Additional observed effects of ROFA included induction of cardiac arrhythmias and increased mortality. These results demonstrate a distinct cardiac component to ROFA toxicity that agrees with epidemiological findings of PM-related excess cardiovascular mortality. Furthermore, the dose-related hypothermia and bradycardia observed in rodents from this study may confound the interpretation of results from similar air pollution toxicology studies. PMID- 26368519 TI - Statistical Analysis of On-Road Particulate Matter Emissions from Diesel Vehicles. AB - During 1996 and 1997, a number of light-and heavy-duty diesel vehicles were recruited in the Denver metropolitan area and subjected to emissions testing, principally for the purposes of assessing on-road particulate emissions. Little if any comparable data had been collected at altitude, particularly from heavy duty vehicles. When these data were statistically examined using the technique of analysis of variance, they were shown both to exceed the federal standards, on average, and to be highly variable. These findings suggest that typically reported average values of vehicular PM emissions are not sufficient to be used, by themselves, to estimate contamination levels and associated public health risk. The situation is exacerbated in studies involving small numbers of vehicles, which is typical when diesel vehicles are involved, since not all sources of variation can be simultaneously controlled. Precise knowledge of the amount of particulates emitted by diesel vehicles in actual daily use is important because of present government strategies designed to promote the use of diesel as a transportation fuel. PMID- 26368520 TI - Development and Validation of a High-Volume, Low-Cutoff Inertial Impactor. AB - A low-cutoff, high-volume conventional impactor has been designed. This sampler uses a slit-shaped acceleration jet and operates at 1100 L/min. The impaction substrate is polyurethane foam (PUF). The impactor collection efficiency was characterized using polydisperse particles, and the 50% size cutoff point was 0.12 !m. Losses within the sampler were also characterized and were less than 10%. The use of polyurethane foam (PUF) as a substrate has the following advantages: (I) PUF has a very high particle collection efficiency over a large range of particle sizes, even under conditions of heavy particle loading, as compared to other impaction substrates, such as flat plates and less porous membranes, which typically are subject to significant bounce-off and reentrainment; (2) no oil or grease coating is required, so potential interferences of impurities within such coatings are avoided when chemical, biological, and toxicological tests are performed on the collected particles; (3) PUF itself is chemically inert, minimizing interference with any of these tests; (4) because of the high flow rate of 1100 L/min, a large amount of particles can be collected in a short period of time on a relatively small surface of substrate, facilitating recovery of the collected particles for the different tests; and (5) a large amount of particles can be collected on a relatively small collection surface and easily extracted with small amounts of water or organic solvents. This method will be suitable for the collection of large amounts for toxicological studies and analysis of organic aerosols, which is not possible with other high-volume samplers that utilize large filtration surfaces. PMID- 26368521 TI - Activation of the Autonomic Nervous System and Blood Coagulation in Association with an Air Pollution Episode. AB - Air pollution has been associated with increases in hospital admissions for cardiovascular diseases. This article aims to identify subgroups of individuals who exhibit early biological responses consistent with the health effects of ambient air pollution. Resting heart rates have been recorded in a cohort of 2681 men and women aged 25-64 yr who participated in the MONICA Augsburg survey during the winter 1984/1985 and in a reexamination during the winter 1987/1988. Increases in heart rate of 1.8 beats per minute (bpm) (95% confidence interval: 0.7 to 2.8 bpm) were observed during the air pollution episode compared to nonepisode days, adjusted for potential cardiovascular risk factors and meteorological parameters. Among persons whose plasma viscosity was above the 90th percentile, heart rates increased 5.1 bpm (95% confidence interval: 2.1 to 8.2 bpm) during the air pollution episode. Persons with normal values of plasma viscosity only had an increase of 1.4 bpm (95% confidence interval: 0.3 to 2.5 bpm) during the air pollution episode. Subjects with increased plasma viscosity showed a more pronounced acceleration in heart rate at rest, pointing toward a modification of the autonomic control of the heart during an air pollution episode. PMID- 26368522 TI - Investigation of Chronic Toxic and Carcinogenic Effects of Gasoline Engine Exhausts Deriving from Fuel without and with Ferrocene Additive. AB - Chronic toxic and carcinogenic effects of gasoline engine exhaust inhalation were investigated in rats. The exhaust from the combustion of commercial fuel containing 30 ppm ferrocene additive was compared to exhaust from the same fuel without ferrocene. This study was part of a procedure to get a special authorization for the use of ferrocene as gasoline additive according to the German Gasoline Lead Act. To generate the exhausts, pairs of engines of the same type and age were operated on computer-controlled test benches in a combined urban-freeway driving cycle. The engines were equipped with three-way catalysts and lambda sensors. Rats inhaled the exhausts after dilution at ratios of about 1.20 and 1:40 for 18 h/day, 5 days/wk for 12 mo (chronic toxicity study) or for 24 mo followed by 6 mo of clean air (carcinogenicity study). The limiting factor for the exhaust concentration was the relative humidity of the exposure atmosphere. At defined intervals, body weight and food consumption, parameters of clinical chemistry, hematology, bronchoalveolar lavage (BAL), and mechanical lung function were measured, as well as lung clearance and particle retention in the lungs. In the high-dose groups and the controls the complete organ/tissue spectrum was investigated histopathologically, and in the low-dose groups the respiratory tract. Only slight exposure-related effects could be detected, like a loss in the background iron content of the cell pellet of the bronchoalveolar lavage fluid and cytoplasmic inclusions and goblet-cell hyperplasias in the nasal cavity. Between the clean-air controls and the exhaust-exposed groups, no exposure-related differences occurred in body weight development, mortality incidences, or any of the clinical investigations. Ninety-two to 94% of the animals developed age-related tumors, predominantly in the mammary glands, uterus, adrenals, thyroid, and pituitary. In the respiratory tract a total of five tumors was found: one in the controls and four in the low-dose groups. No physical, chemical, or toxicological differences between the exhausts from fuel without or with ferrocene were demonstrated. PMID- 26368523 TI - Ultrafine Particle Concentrations in a Hospital. AB - Ultrafine particles (UFP) may contribute to the morbidity and mortality associated with exposure to ambient particles, but few data are available on ultrafine particle numbers in indoor air, where susceptible subjects spend most of their time. We measured particle number, UFP size distribution, and total suspended particulate (JSP) mass in three locations: (I) a medical floor in a large tertiary care hospital, (2) outdoor air above a construction site outside the hospital, and (3) an environmental exposure chamber with purification of intake air. Mass and number concentrations were recorded continuously in each location over 70-110 h. Mean +/- SD particle (p) numbers were 3.63 +/- 1.l5 } 10(3) p/cm(3) in the hospital, 3.05 +/- 6.65 } 10(4) p/cm(3) outside, and 5.86 +/ 2.11 } 10(2) p/cm(3) in the environmental chamber. In the hospital, particle number and mass declined during the evening hours when the unit was less active, with the particle number as low as 1.15 } 10(3) p/cm(3). Particle numbers peaked (2.78 } 10(4) p/cm(3)) in the morning hours when activity on the unit was the most intense. "Spikes" in fine particle number were often not accompanied by increases in TSP mass. In the hospital, a distinct population of ultrafine particles (median diameter approximately 23 nm) was observed during the lunch hour, suggesting a change in particle source during this time. Outdoor fine particle numbers above the construction site were highly variable, reaching peaks of greater than 1.7 } 10(6) p/cm(3). These data suggest that, in the indoor environment, particle numbers and size distribution vary with intensity and type of local activity, and significant peaks in particle number are not detected with daily averages. Monitoring of particle mass may be an inaccurate measure of exposure to ultrafine particles indoors. PMID- 26368524 TI - A Chemical and Toxicological Comparison of Urban Air PM10 Collected During Winter and Spring in Finland. AB - We have used a new high-volume, low-cutoff inertial impactor (HVLI) in a pilot study on chemical characterization and toxicity testing of ambient air PM10 in Helsinki, Finland. Ambient air PM10 was collected at 1100 L/min in 2- to 4-day periods. Two different PM10 samples were selected to represent wintertime combustion type and springtime resuspension type particulate matter (PM) pollution. The most abundant water-soluble ions and elements were analyzed by ion chromatography and inductively coupled plasma mass spectrometry, respectively. The proinflammatory activation !NO and interleukin 6 (IL-6) production] and viability of cultured murine RAW 264.7 macrophages were tested in 24-h incubations with increasing mass doses (30-2000 ug per 10(6) cells) from the collected PM10 samples. The winter sample had a higher assessed PM2.5 fraction and sulfate content, and lower chloride, sodium, calcium, aluminum, copper, manganese, and especially iron contents than the spring sample. Both PMjo samples induced dose-dependent NO production in murine macrophages, and the springtime PM10 produced also a strong, dose-dependent IL-6 production. In conclusion, the HVLI proved to be a suitable technique for short-term collection of relatively large ambient air PM masses, enabling extensive chemical characterization and toxicity testing from the same samples. PMID- 26368525 TI - Particulate Matter Induction of Pulmonary Gelatinase A, Gelatinase B, and Tissue Inhibitor of Metalloproteinase Expression. AB - Gelatinase A and gelatinase B are matrix metalloproteinases (MMPs) that are capable of degrading type IV collagen as well as other major components of basement membranes. These MMPs are also involved in modulating inflammation and tissue remodeling. Previous studies have shown the induction of pulmonary matrilysin, another MMP, following exposure to either combustion or ambient particulate matter (PM). In the present study, we examined whether gelatinase A, gelatinase B, or tissue inhibitor of metalloproteinase (TIMP) was affected following exposure to PM. Sprague-Dawley rats were exposed to a combustion PM (residual oil fly ash, ROTA, 2.5 mg/rat) or saline by intratracheal instillation and examined at 6 to 72 h postexposure. Changes in gelatinase A, gelatinase B, and TIMP-1 and -2 m RNA levels were determined using reverse transcription (RT) polymerase chain reaction (PCR). ROTA exposure increased the mRNA levels of gelatinase A and TIMP-1. However, gelatinase B mRNA, not expressed in control animals, was significantly induced from 6 to 24 h following ROFA exposure. Western blot analysis confirmed the presence of gelatinase A and B protein in lung tissue following ROFA exposure. Immunocytochemical analysis revealed that alveolar epithelial cells and inflammatory cells were major cellular sources for the pulmonary gelatinase A and B expression. To compare the effects of ambient PM with that of combustion PM and to further examine effects of ambient PM size on MMP induction, animals were treated with the same dose of the size-fractionated ambient PM [PM1.7, PM1.7-3.7, PM37.20 (size indicated in micrometers) collected from Washington, DC], Gelatinase A, gelatinase B, and TIMP gene expression and cellular distributions were assessed using RT-PCR and immunocytochemistry, respectively. Interestingly, gelatinase B was significantly induced to the same extent by all three size-fractionated ambient PM. Celatinase A and TIMP-1 expression were not changed, while TIMP-2 expression was slightly decreased by PM1.7 and PM1.7-3.7. Immunocytochemically, gelatinase A, gelatinase B, and TIMP-2 expression were localized mainly to the terminal bronchiole region and associated with inflammatory cells in ambient PM exposed animals. Thus, we have provided further evidence that MMP and TIMP expression are altered following exposure to either combustion or ambient PM supporting the hypothesis that MMP may be involved in pathogenesis of PM-induced lung injury. PMID- 26368526 TI - An Exploratory Analysis of the Relationship Between Mortality and the Chemical Composition of Airborne Particulate Matter. AB - We explored relationships between daily mortality and the major sources of airborne particulate matter (PM) using a newly developed approach, Factor Analysis and Poisson Regression (FA/PR). We hypothesized that by adding information on PM chemical speciation and source apportionment to typical PM epidemiological analysis, we could identify PM sources that cause adverse health effects. The FA/PR method was applied to a merged data set of mortality and extensive PM chemical speciation (including trace metals, sulfate, and extractable organic matter) in New Jersey. Statistically significant associations were found between mortality and several of the FA-derived PM sources, including oil burning, industry, sulfate aerosol, and motor vehicles. The FA/PR method provides new insight into potentially important PM sources related to mortality. For the data set we analyzed, the use of FA/PR to integrate multiple chemical species into source-related PM exposure metrics was found to be a more sensitive tool than the traditional approach using PM mass alone. PMID- 26368527 TI - Colloquium Abstracts. PMID- 26368528 TI - Preface. PMID- 26368529 TI - Forearm Range of Motion in Australovenator wintonensis (Theropoda, Megaraptoridae). AB - The hypertrophied manual claws and modified manus of megaraptoran theropods represent an unusual morphological adaptation among carnivorous dinosaurs. The skeleton of Australovenator wintonensis from the Cenomanian of Australia is among the most complete of any megaraptorid. It presents the opportunity to examine the range of motion of its forearm and the function of its highly modified manus. This provides the basis for behavioural inferences, and comparison with other Gondwanan theropod groups. Digital models created from computed tomography scans of the holotype reveal a humerus range of motion that is much greater than Allosaurus, Acrocanthosaurus, Tyrannosaurus but similar to that of the dromaeosaurid Bambiraptor. During flexion, the radius was forced distally by the radial condyle of the humerus. This movement is here suggested as a mechanism that forced a medial movement of the wrist. The antebrachium possessed a range of motion that was close to dromaeosaurids; however, the unguals were capable of hyper-extension, in particular manual phalanx I-2, which is a primitive range of motion characteristic seen in allosaurids and Dilophosaurus. During flexion, digits I and II slightly converge and diverge when extended which is accentuated by hyperextension of the digits in particular the unguals. We envision that prey was dispatched by its hands and feet with manual phalanx I-2 playing a dominant role. The range of motion analysis neither confirms nor refutes current phylogenetic hypotheses with regards to the placement of Megaraptoridae; however, we note Australovenator possessed, not only a similar forearm range of motion to some maniraptorans and basal coelurosaurs, but also similarities with Tetanurans (Allosauroids and Dilophosaurus). PMID- 26368530 TI - Pseudomonas aeruginosa Uses Dihydrolipoamide Dehydrogenase (Lpd) to Bind to the Human Terminal Pathway Regulators Vitronectin and Clusterin to Inhibit Terminal Pathway Complement Attack. AB - The opportunistic human pathogen Pseudomonas aeruginosa controls host innate immune and complement attack. Here we identify Dihydrolipoamide dehydrogenase (Lpd), a 57 kDa moonlighting protein, as the first P. aeruginosa protein that binds the two human terminal pathway inhibitors vitronectin and clusterin. Both human regulators when bound to the bacterium inhibited effector function of the terminal complement, blocked C5b-9 deposition and protected the bacterium from complement damage. P. aeruginosa when challenged with complement active human serum depleted from vitronectin was severely damaged and bacterial survival was reduced by over 50%. Similarly, when in human serum clusterin was blocked by a mAb, bacterial survival was reduced by 44%. Thus, demonstrating that Pseudomonas benefits from attachment of each human regulator and controls complement attack. The Lpd binding site in vitronectin was localized to the C-terminal region, i.e. to residues 354-363. Thus, Lpd of P. aeruginosa is a surface exposed moonlighting protein that binds two human terminal pathway inhibitors, vitronectin and clusterin and each human inhibitor when attached protected the bacterial pathogen from the action of the terminal complement pathway. Our results showed insights into the important function of Lpd as a complement regulator binding protein that might play an important role in virulence of P. aeruginosa. PMID- 26368531 TI - Characterization of the Bacterioferritin/Bacterioferritin Associated Ferredoxin Protein-Protein Interaction in Solution and Determination of Binding Energy Hot Spots. AB - Mobilization of iron stored in the interior cavity of BfrB requires electron transfer from the [2Fe-2S] cluster in Bfd to the core iron in BfrB. A crystal structure of the Pseudomonas aeruginosa BfrB:Bfd complex revealed that BfrB can bind up to 12 Bfd molecules at 12 structurally identical binding sites, placing the [2Fe-2S] cluster of each Bfd immediately above a heme group in BfrB [Yao, H., et al. (2012) J. Am. Chem. Soc., 134, 13470-13481]. We report here study aimed at characterizing the strength of the P. aeruginosa BfrB:Bfd association using surface plasmon resonance and isothermal titration calorimetry as well as determining the binding energy hot spots at the protein-protein interaction interface. The results show that the 12 Bfd-binding sites on BfrB are equivalent and independent and that the protein-protein association at each of these sites is driven entropically and is characterized by a dissociation constant (Kd) of approximately 3 MUM. Determination of the binding energy hot spots was carried out by replacing certain residues that comprise the protein-protein interface with alanine and by evaluating the effect of the mutation on Kd and on the efficiency of core iron mobilization from BfrB. The results identified hot spot residues in both proteins [LB 68, EA 81, and EA 85 in BfrB (superscript for residue number and subscript for chain) and Y2 and L5 in Bfd] that network at the interface to produce a highly complementary hot region for the interaction. The hot spot residues are conserved in the amino acid sequences of Bfr and Bfd proteins from a number of Gram-negative pathogens, indicating that the BfrB:Bfd interaction is of widespread significance in bacterial iron metabolism. PMID- 26368532 TI - Investigation on the Tribological Behavior and Wear Mechanism of Five Different Veneering Porcelains. AB - OBJECTIVES: The primary aim of this research was to investigate the wear behavior and wear mechanism of five different veneering porcelains. METHODS: Five kinds of veneering porcelains were selected in this research. The surface microhardness of all the samples was measured with a microhardness tester. Wear tests were performed on a ball-on-flat PLINT fretting wear machine, with lubrication of artificial saliva at 37 degrees C. The friction coefficients were recorded by the testing system. The microstructure features, wear volume, and damage morphologies were recorded and analyzed with a confocal laser scanning microscope and a scanning electron microscope. The wear mechanism was then elucidated. RESULTS: The friction coefficients of the five veneering porcelains differ significantly. No significant correlation between hardness and wear volume was found for these veneering porcelains. Under lubrication of artificial saliva, the porcelain with higher leucite crystal content exhibited greater wear resistance. Additionally, leucite crystal size and distribution in glass matrix influenced wear behavior. The wear mechanisms for these porcelains were similar: abrasive wear dominates the early stage, whereas delamination was the main damage mode at the later stage. Furthermore, delamination was more prominent for porcelains with larger crystal sizes. SIGNIFICANCE: Wear compatibility between porcelain and natural teeth is important for dental restorative materials. Investigation on crystal content, size, and distribution in glass matrix can provide insight for the selection of dental porcelains in clinical settings. PMID- 26368534 TI - Correction: Electrically Stimulated Antagonist Muscle Contraction Increased Muscle Mass and Bone Mineral Density of One Astronaut--Initial Verification on the International Space Station. PMID- 26368533 TI - Strain-Dependent Effect of Macroautophagy on Abnormally Folded Prion Protein Degradation in Infected Neuronal Cells. AB - Prion diseases are neurodegenerative disorders caused by the accumulation of abnormal prion protein (PrPSc) in the central nervous system. With the aim of elucidating the mechanism underlying the accumulation and degradation of PrPSc, we investigated the role of autophagy in its degradation, using cultured cells stably infected with distinct prion strains. The effects of pharmacological compounds that inhibit or stimulate the cellular signal transduction pathways that mediate autophagy during PrPSc degradation were evaluated. The accumulation of PrPSc in cells persistently infected with the prion strain Fukuoka-1 (FK), derived from a patient with Gerstmann-Straussler-Scheinker syndrome, was significantly increased in cultures treated with the macroautophagy inhibitor 3 methyladenine (3MA) but substantially reduced in those treated with the macroautophagy inducer rapamycin. The decrease in FK-derived PrPSc levels was mediated, at least in part, by the phosphatidylinositol 3-kinase/MEK signalling pathway. By contrast, neither rapamycin nor 3MA had any apparently effect on PrPSc from either the 22L or the Chandler strain, indicating that the degradation of PrPSc in host cells might be strain-dependent. PMID- 26368535 TI - Molecular Fingerprint and Dominant Environmental Factors of Nitrite-Dependent Anaerobic Methane-Oxidizing Bacteria in Sediments from the Yellow River Estuary, China. AB - Nitrite-dependent anaerobic methane oxidation (n-damo) is performed by "Candidatus Methylomirabilis oxyfera" (M. oxyfera), which connects the carbon and nitrogen global nutrient cycles. In the present study, M. oxyfera-like bacteria sequences were successfully recovered from Yellow River Estuary sediments using specific primers for 16S rRNA and pmoA genes. A M. oxyfera-like sequences analysis based on the 16S rRNA gene revealed greater diversity compared with the pmoA gene; the 16S rRNA gene sequences retrieved from the Yellow River Estuary sediments belong to groups A as well as B and were mainly found in freshwater habitats. Quantitative PCR showed that 16S rRNA gene abundance varied from 9.28+/ 0.11*10(3) to 2.10+/-0.13*10(5) copies g(-1) (dry weight), and the pmoA gene abundance ranged from 8.63+/-0.50*10(3) to 1.83+/-0.18*10(5) copies g(-1) (dry weight). A correlation analysis showed that the total organic carbon (TOC) and ammonium (NH4(+)) as well as the ratio of total phosphorus to total nitrogen (TP/TN) influenced the M. oxyfera-like bacteria distribution in the Yellow River Estuary sediments. These findings will aid in understanding the n-damo bacterial distribution pattern as well as their correlation with surrounding environmental factors in temperate estuarine ecosystems. PMID- 26368536 TI - Insights into the binding of thiosemicarbazone derivatives with human serum albumin: spectroscopy and molecular modelling studies. AB - 4-[(1Z)-1-(2-carbamothioylhydrazinylidene)ethyl]phenyl acetate [Ace semi],4-[(1Z) 1-(2-carbamothioylhydrazinylidene)ethyl]phenyl propanoate [Pro semi] from the family of thiosemicarbazones derivative has been newly synthesized. It has good anticancer activity as well as antibacterial and it is also less toxic in nature, its binding characteristics are therefore of huge interest for understanding pharmacokinetic mechanism of the drug. The binding of thiosemicarbazone derivative to human serum albumin (HSA) has been investigated by studying its quenching mechanism, binding kinetics and the molecular distance (r) between donor (HSA) and acceptor (thiosemicarbazone derivative) was estimated according to Forster's theory of non-radiative energy transfer using fluorescence spectroscopy. The binding dynamics has been elaborated using synchronous fluorescence spectroscopy, and the feature of thiosemicarbazone derivative induced structural changes of HSA has been studied by circular dichorism, Fourier transform infrared spectroscopy. Molecular modelling simulations explore the hydrophobic interaction and hydrogen bonding which stabilizes the interaction. PMID- 26368537 TI - Profitability of Contrarian Strategies in the Chinese Stock Market. AB - This paper reexamines the profitability of loser, winner and contrarian portfolios in the Chinese stock market using monthly data of all stocks traded on the Shanghai Stock Exchange and Shenzhen Stock Exchange covering the period from January 1997 to December 2012. We find evidence of short-term and long-term contrarian profitability in the whole sample period when the estimation and holding horizons are 1 month or longer than 12 months and the annualized return of contrarian portfolios increases with the estimation and holding horizons. We perform subperiod analysis and find that the long-term contrarian effect is significant in both bullish and bearish states, while the short-term contrarian effect disappears in bullish states. We compare the performance of contrarian portfolios based on different grouping manners in the estimation period and unveil that decile grouping outperforms quintile grouping and tertile grouping, which is more evident and robust in the long run. Generally, loser portfolios and winner portfolios have positive returns and loser portfolios perform much better than winner portfolios. Both loser and winner portfolios in bullish states perform better than those in the whole sample period. In contrast, loser and winner portfolios have smaller returns in bearish states, in which loser portfolio returns are significant only in the long term and winner portfolio returns become insignificant. These results are robust to the one-month skipping between the estimation and holding periods and for the two stock exchanges. Our findings show that the Chinese stock market is not efficient in the weak form. These findings also have obvious practical implications for financial practitioners. PMID- 26368538 TI - Exercise in knee osteoarthritis--preliminary findings: Exercise-induced pain and health status differs between drop-outs and retainers. AB - BACKGROUND: Exercise effectiveness is related to adherence, compliance and drop out. The aim of this study is to investigate if exercise-induced pain and health status are related to these outcomes during two exercise programs in knee osteoarthritis patients. METHODS: Symptomatic knee osteoarthritis patients were randomly allocated to a walking or strengthening program (N=19/group). At baseline, patients were categorized according to their health status. Exercise adherence and compliance were calculated and drop-out rate was registered. For exercise-induced pain, patients rated their pain on an 11-point numeric rating scale (NRS) before and after each training session. Before each session the maximal perceived pain of the last 24h (NRSmax24) was assessed. Patients rated their global self-perceived effect (GPE) on a 7-point ordinal scale after the intervention period. RESULTS: 53% of the participants felt they improved after the program, 6 patients dropped out. The mean adherence and compliance rates were higher than .83 in both groups. Worse health and higher exercise-induced pain were seen in drop-outs. NRSmax24 during the first 3 weeks did not significantly increase compared to baseline, but correlated negatively with adherence during the home sessions (-.56, p<.05). Lower adherence during supervised sessions was significantly related with higher pre-exercise pain scores (rho=-.35, p<.05). CONCLUSION: Patients who drop-out show a worse health condition and higher exercise-induced pain levels compared to patients that retained the program. PMID- 26368539 TI - Does tooth wear influence ageing? A comparative study across large herbivores. AB - We test whether the intensity of tooth wear influences the strength of actuarial senescence across species of large herbivores. We collected from the literature data on tooth wear in the wild (measured as the slope of the regression of log transformed M1 crown height on age), longevity (measured as the age at which 90% of individuals are dead) and two metrics of actuarial senescence in captive populations (rate of senescence between 6 and 12 years of age and Gompertz rate of senescence). Between-species differences and variation in tooth height accounted for most of the observed variation in tooth wear among large herbivores: tooth height and tooth wear were positively correlated. In contrast, tooth wear was little influenced by sex, body mass, or taxonomy. No marked between-sex differences in longevity occurred. Males senesced faster than females when tooth wear was low (for both senescence metrics), while between-sex differences in actuarial senescence when tooth wear was high depended on the metric used to measure actuarial senescence. While longevity was mostly independent of the intensity of tooth wear, we found general support for a positive relationship between both measures of actuarial senescence and tooth wear. These patterns were consistent whether hypsodonty was controlled for or not. Although varying according to sex and to the metric used for assessing actuarial senescence, our findings suggest overall that tooth wear could be positively associated with actuarial senescence among large herbivores. Further longitudinal studies focusing on changes within individuals will be required to test whether a mechanistic link between tooth wear and actuarial senescence occurs in large herbivores. PMID- 26368540 TI - The diurnal profile of melatonin during delirium in elderly patients--preliminary results. AB - Delirium is an acute-onset syndrome that exacerbates patients' condition and significantly increases consequential morbidity and mortality. There is no comprehensive, cellular and tissue-level, pathophysiological theory. The melatonin hormone imbalance has been shown to be linked to circadian rhythms, sleep-wake cycle disturbances, and delirium incidence. There has been relatively little research about melatonin in delirium, and there has been no such study done in the group of elderly patients of a general medicine ward yet. The aim of our study was to compare melatonin hormone concentration in relation to the presence of delirium in elderly patients hospitalized in the general medicine ward. Blood samples were collected four times a day for two days (at 12:00, 18:00, 00:00 and 6:00), on the day when delirium was diagnosed and 72 h after the delirium resolution. Delirium was diagnosed with the Confusion Assessment Method and the criteria of the Diagnostic and Statistic Manual of Mental Disorders, 4th Revision. The mean age of 30 patients (73.3% women) was 86.5 +/- 5.2 years. Delirium was diagnosed most often on the second and third day of hospitalization. A lot of predisposing and precipitating factors for delirium were identified. There was a significant difference in the melatonin hormone concentration measurement at 12:00 when patients had acute delirium and after its resolution [18.5 (13.8, 27.5) vs 12.9 (9.8, 17.8), p<0.01]. Different patterns of the melatonin hormone concentration were shown in analyses in the subgroups defined according to the patients' diagnosis of dementia. We found that the delirium recovery was, in fact, associated with the alteration of the daily profile of melatonin. PMID- 26368541 TI - An Integrated Approach of Fuzzy Linguistic Preference Based AHP and Fuzzy COPRAS for Machine Tool Evaluation. AB - Globalization of business and competitiveness in manufacturing has forced companies to improve their manufacturing facilities to respond to market requirements. Machine tool evaluation involves an essential decision using imprecise and vague information, and plays a major role to improve the productivity and flexibility in manufacturing. The aim of this study is to present an integrated approach for decision-making in machine tool selection. This paper is focused on the integration of a consistent fuzzy AHP (Analytic Hierarchy Process) and a fuzzy COmplex PRoportional ASsessment (COPRAS) for multi attribute decision-making in selecting the most suitable machine tool. In this method, the fuzzy linguistic reference relation is integrated into AHP to handle the imprecise and vague information, and to simplify the data collection for the pair-wise comparison matrix of the AHP which determines the weights of attributes. The output of the fuzzy AHP is imported into the fuzzy COPRAS method for ranking alternatives through the closeness coefficient. Presentation of the proposed model application is provided by a numerical example based on the collection of data by questionnaire and from the literature. The results highlight the integration of the improved fuzzy AHP and the fuzzy COPRAS as a precise tool and provide effective multi-attribute decision-making for evaluating the machine tool in the uncertain environment. PMID- 26368542 TI - Comparison of the Prognostic Value of F-18 Pet Metabolic Parameters of Primary Tumors and Regional Lymph Nodes in Patients with Locally Advanced Cervical Cancer Who Are Treated with Concurrent Chemoradiotherapy. AB - OBJECTIVE: This study investigated the metabolic parameters of primary tumors and regional lymph nodes, as measured by pre-treatment F-18 fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) to compare the prognostic value for the prediction of tumor recurrence. This study also identified the most powerful parameter in patients with locally advanced cervical cancer treated with concurrent chemoradiotherapy. METHODS: Fifty-six patients who were diagnosed with cervical cancer with pelvic and/or paraaortic lymph node metastasis were enrolled in this study. Metabolic parameters including the maximum standardized uptake value (SUVmax), the metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary tumors and lymph nodes were measured by pre-treatment F-18 FDG PET/CT. Univariate and multivariate analyses for disease-free survival (DFS) were performed using the clinical and metabolic parameters. RESULTS: The metabolic parameters of the primary tumors were not associated with DFS. However, DFS was significantly longer in patients with low values of nodal metabolic parameters than in those with high values of nodal metabolic parameters. A univariate analysis revealed that nodal metabolic parameters (SUVmax, MTV and TLG), paraaortic lymph node metastasis, and post treatment response correlated significantly with DFS. Among these parameters, nodal SUVmax (hazard ratio [HR], 4.158; 95% confidence interval [CI], 1.1-22.7; p = 0.041) and post-treatment response (HR, 7.162; 95% CI, 1.5-11.3; p = 0.007) were found to be determinants of DFS according to a multivariate analysis. Only nodal SUVmax was an independent pre-treatment prognostic factor for DFS, and the optimal cutoff for nodal SUVmax to predict progression was 4.7. CONCLUSION: Nodal SUVmax according to pre-treatment F-18 FDG PET/CT may be a prognostic biomarker for the prediction of disease recurrence in patients with locally advanced cervical cancer. PMID- 26368544 TI - Restless Sleep in a Hyperactive Girl: A Paradoxical Adverse Reaction to Methylphenidate. PMID- 26368543 TI - Critical Function of gammaH2A in S-Phase. AB - Phosphorylation of histone H2AX by ATM and ATR establishes a chromatin recruitment platform for DNA damage response proteins. Phospho-H2AX (gammaH2AX) has been most intensively studied in the context of DNA double-strand breaks caused by exogenous clastogens, but recent studies suggest that DNA replication stress also triggers formation of gammaH2A (ortholog of gammaH2AX) in Schizosaccharomyces pombe. Here, a focused genetic screen in fission yeast reveals that gammaH2A is critical when there are defects in Replication Factor C (RFC), which loads proliferating cell nuclear antigen (PCNA) clamp onto duplex DNA. Surprisingly Chk1, Cds1/Chk2 and the Rad9-Hus1-Rad1 checkpoint clamp, which are crucial for surviving many genotoxins, are fully dispensable in RFC-defective cells. Immunoblot analysis confirms that Rad9-Hus1-Rad1 is not required for formation of gammaH2A by Rad3/ATR in S-phase. Defects in DNA polymerase epsilon, which binds PCNA in the replisome, also create an acute need for gammaH2A. These requirements for gammaH2A were traced to its role in docking with Brc1, which is a 6-BRCT-domain protein that is structurally related to budding yeast Rtt107 and mammalian PTIP. Brc1, which localizes at stalled replication forks by binding gammaH2A, prevents aberrant formation of Replication Protein A (RPA) foci in RFC impaired cells, suggesting that Brc1-coated chromatin stabilizes replisomes when PCNA or DNA polymerase availability limits DNA synthesis. PMID- 26368546 TI - Observational case series on adalimumab-induced paradoxical hidradenitis suppurativa. AB - INTRODUCTION: Although the efficacy of TNF blockers has been demonstrated in hidradenitis suppurativa (HS), many paradoxical effects have also been described with TNF antagonists. We wished to describe patients with adalimumab (ADA) induced paradoxical HS. METHODS: This is a retrospective descriptive case series of four patients with ADA-induced paradoxical HS. RESULTS: All the patients had a good response to TNFa antagonist therapy at the time of HS occurrence. The time from TNFa antagonist initiation to HS onset or exacerbation ranged from a few weeks to 24 months. The outcome of HS was variable. Systemic antibiotics were required in all the cases to control HS. TNF blockers were continued in three cases with a switch to another anti-TNF class in one case. Switch to ustekinumab was prescribed in one patient with SA and Crohn's disease. CONCLUSION: Although the imputability of TNF blockers in paradoxical HS is still debatable, further research and observation are needed to confirm and distinguish patients with genetic and clinical predisposition in the onset or exacerbation of HS during anti-TNF treatment. PMID- 26368548 TI - Synchronous Hepatoblastoma, Neuroblastoma, and Cutaneous Capillary Hemangiomas: A Case Report. AB - Multiple synchronous tumors presenting in infancy raise concern for inherited or sporadic cancer predisposition syndromes, which include Beckwith-Wiedemann syndrome, familial adenomatous polyposis syndrome, and Li-Fraumeni syndrome. We report a case of a 7-month-old previously healthy male born following an in vitro fertilization-assisted twin pregnancy who presented with new-onset refractory shock, severe acidosis, and rapid decline over several hours. An autopsy revealed a ruptured liver involved by hepatoblastoma, an adrenal gland involved by neuroblastoma, and multiple cutaneous capillary hemangiomas. Standard genetic testing demonstrated that both twins were Gaucher disease (GD) carriers without evidence of other known cancer predisposition syndromes. This report describes a unique association of multiple synchronous tumors, which underscores the utility and importance of the pediatric autopsy. Moreover, given that the reported child was a GD carrier, the possibility the tumors were the result of a GD-mediated cancer-associated phenotype or an unrecognized sporadic clinical syndrome remains an unanswered, but intriguing, question worthy of further investigation. PMID- 26368549 TI - SATRAP: SOLiD Assembler TRAnslation Program. AB - SOLiD DNA sequences are typically analyzed using a reference genome, while they are not recommended for de novo assembly of genomes or transcriptomes. This is mainly due to the difficulty in translating the SOLiD color-space data into normal base-space sequences. In fact, the nature of color-space is such that any misinterpreted color leads to a chain of further translation errors, producing totally wrong results. Here we describe SATRAP, a computer program designed to efficiently translate de novo assembled color-space sequences into a base-space format. The program was tested and validated using simulated and real transcriptomic data; its modularity allows an easy integration into more complex pipelines, such as Oases for RNA-seq de novo assembly. SATRAP is available at http://satrap.cribi.unipd.it, either as a multi-step pipeline incorporating several tools for RNA-seq assembly or as an individual module for use with the Oases package. PMID- 26368550 TI - Prognostic Impact of Placental Growth Factor on Mortality and Cardiovascular Events in Dialysis Patients. AB - BACKGROUND: Placental growth factor (PlGF), a member of the vascular endothelial growth factor (VEGF) family, has recently emerged as a predictor of survival and cardiovascular risk. Along with others, we have shown an independent association between PlGF and cardiovascular events in CKD patients, but not much is known about patients receiving dialysis. METHODS: We studied 205 dialysis patients undergoing cardiac catheterization at the Nara Medical University between April 1, 2004, and December 31, 2012. Serum levels of PlGF and VEGF were measured with ELISA in all the patients. RESULTS: During a median follow-up of 20 months, 121 participants died from any cause or experienced a cardiovascular event. In the fully adjusted analysis, having an above-median PlGF or VEGF level was associated with a hazards ratio for adverse outcomes of 2.55 (1.72-3.83) and 1.39 (0.95 2.04), respectively. Using a multimarker strategy in a model with age, serum albumin, history of coronary artery disease, brain natriuretic peptide and PlGF, patients with 2, 3 and 4 positive markers had a 3.82-, 5.77- and 6.59-fold higher risk of mortality or a cardiovascular event, respectively, compared to those with no positive markers. The model with PlGF had a significantly higher c-statistic, integrated discrimination improvement index and category-free net reclassification improvement index than the model without PlGF. CONCLUSION: PlGF is independently associated with mortality and cardiovascular events, but the association between VEGF and adverse events was attenuated with covariate adjustment. The addition of PlGF to models with established clinical predictors provides additional useful prognostic information in patients receiving dialysis. PMID- 26368551 TI - Selective Retina Therapy in Acute and Chronic-Recurrent Central Serous Chorioretinopathy. AB - PURPOSE: Selective retina therapy (SRT), the confined laser heating and destruction of retinal pigment epithelial cells, has been shown to treat acute types of central serous chorioretinopathy (CSC) successfully without damaging the photoreceptors and thus avoiding laser-induced scotoma. However, a benefit of laser treatment for chronic forms of CSC is questionable. In this study, the efficacy of SRT by means of the previously used 1.7-us and shorter 300-ns pulse duration was evaluated for both types of CSC, also considering re-treatment for nonresponders. MATERIAL AND METHODS: In a two-center trial, 26 patients were treated with SRT for acute (n = 10) and chronic-recurrent CSC (n = 16). All patients presented with subretinal fluid (SRF) in OCT and leakage in fluorescein angiography (FA). SRT was performed using a prototype SRT laser system (frequency doubled Q-switched Nd:YLF-laser, wavelength 527 nm) with adjustable pulse duration. The following irradiation settings were used: a train of 30 laser pulses with a repetition rate of 100 Hz and pulse durations of 300 ns and 1.7 us, pulse energy 120-200 uJ, retinal spot size 200 um. Because SRT lesions are invisible, FA was always performed 1 h after treatment to demonstrate laser outcome (5-8 single spots in the area of leakage). In cases where energy was too low, as indicated by missing FA leakage, energy was adjusted and the patient re treated immediately. Observation intervals were after 4 weeks and 3 months. In case of nonimprovement of the disease after 3 months, re-treatment was considered. RESULTS: Of 10 patients with active CSC that presents focal leakage in FA, 5 had completely resolved fluid after 4 weeks and all 10 after 3 months. Mean visual acuity increased from 76.6 ETDRS letters to 85.0 ETDRS letters 3 months after SRT. Chronic-recurrent CSC was characterized by less severe SRF at baseline in OCT and weaker leakage in FA than in acute types. Visual acuity changed from baseline 71.6 to 72.8 ETDRS letters after 3 months. At this time, SRF was absent in 3 out of 16 patients (19%), FA leakage had come to a complete stop in 6 out of 16 patients (38%). In 6 of the remaining chronic CSC patients, repeated SRT with higher pulse energy was considered because of persistent leakage activity. After the re-treatment, SRF resolved completely in 5 patients (83.3%) after only 25 days. CONCLUSION: SRT showed promising results in treating acute CSC, but was less effective in chronic cases. Interestingly, re-treatment resulted in enhanced fluid resolution and dry conditions after a considerably shorter time in most patients. Therefore, SRT including re-treatment if necessary might be a valuable CSC treatment alternative even in chronic-recurrent cases. PMID- 26368553 TI - Tailoring Treatment to the Individual Patient - Will Inflammatory Bowel Disease Medicine Be Personalized? AB - Personalized medicine is variably defined as a new system aimed at providing optimal medical care by using comprehensive pathophysiology-based information on all aspects and components of a disease process to prevent, diagnose and treat in ways that are custom-made for the individual patient. The need for personalized medicine derives from the realization that today's most challenging medical conditions are chronic complex diseases with multiple pathogenic components that interact with each other. Complexity and interaction together create unique molecular pathways that are only relevant to certain disease subtypes, but not to the entire population of patients with the same diagnosis. Thus, complex diseases cannot be properly controlled, and much less cured, by modulating single components at sporadic time points in the course of the disease or administering the same treatment to all patients, as we currently do in the management of inflammatory bowel disease (IBD). The implementation of personalized medicine requires entirely novel and methodologically sophisticated bioinformatics-based approaches that use comprehensive and detailed information on the various components ('omes') of the disease process. This requires identifying the key controllers ('hubs') of pathogenic pathways in a totally unbiased fashion and discovering highly specific agents that can selectively block or even revert pathogenic events. IBD is a perfect example of a condition with multiple causes and multiple mechanisms, and IBD patients will unquestionably benefit from the adoption of personalized medicine in the near future. PMID- 26368552 TI - Outcomes of Technical Variant Liver Transplantation versus Whole Liver Transplantation for Pediatric Patients: A Meta-Analysis. AB - OBJECTIVE: To overcome the shortage of appropriate-sized whole liver grafts for children, technical variant liver transplantation has been practiced for decades. We perform a meta-analysis to compare the survival rates and incidence of surgical complications between pediatric whole liver transplantation and technical variant liver transplantation. METHODS: To identify relevant studies up to January 2014, we searched PubMed/Medline, Embase, and Cochrane library databases. The primary outcomes measured were patient and graft survival rates, and the secondary outcomes were the incidence of surgical complications. The outcomes were pooled using a fixed-effects model or random-effects model. RESULTS: The one-year, three-year, five-year patient survival rates and one-year, three-year graft survival rates were significantly higher in whole liver transplantation than technical variant liver transplantation (OR = 1.62, 1.90, 1.65, 1.78, and 1.62, respectively, p<0.05). There was no significant difference in five-year graft survival rate between the two groups (OR = 1.47, p = 0.10). The incidence of portal vein thrombosis and biliary complications were significantly lower in the whole liver transplantation group (OR = 0.45 and 0.42, both p<0.05). The incidence of hepatic artery thrombosis was comparable between the two groups (OR = 1.21, p = 0.61). CONCLUSIONS: Pediatric whole liver transplantation is associated with better outcomes than technical variant liver transplantation. Continuing efforts should be made to minimize surgical complications to improve the outcomes of technical variant liver transplantation. PMID- 26368554 TI - Resistance-Associated NS5A Variants of Hepatitis C Virus Are Susceptible to Interferon-Based Therapy. AB - BACKGROUND & AIMS: The presence of resistance-associated variants (RAVs) of hepatitis C virus (HCV) attenuates the efficacy of direct acting antivirals (DAAs). The objective of this study was to characterize the susceptibility of RAVs to interferon-based therapy. METHODS: Direct and deep sequencing were performed to detect Y93H RAV in the NS5A region. Twenty nine genotype 1b patients with detectable RAV at baseline were treated by a combination of simeprevir, pegylated interferon and ribavirin. The longitudinal changes in the proportion of Y93H RAV during therapy and at breakthrough or relapse were determined. RESULTS: By direct sequencing, Y93H RAV became undetectable or decreased in proportion at an early time point during therapy (within 7 days) in 57% of patients with both the Y93H variant and wild type virus at baseline when HCV RNA was still detectable. By deep sequencing, the proportion of Y93H RAV against Y93 wild type was 52.7% (5.8%- 97.4%) at baseline which significantly decreased to 29.7% (0.16% 98.3%) within 7 days of initiation of treatment (p = 0.023). The proportion of Y93H RAV was reduced in 21 of 29 cases (72.4%) and a marked reduction of more than 10% was observed in 14 cases (48.7%). HCV RNA reduction was significantly greater for Y93H RAV (-3.65+/-1.3 logIU/mL/day) than the Y93 wild type (-3.35+/ 1.0 logIU/mL/day) (p<0.001). CONCLUSION: Y93H RAV is more susceptible to interferon-based therapy than the Y93 wild type. PMID- 26368556 TI - A Novel Virus-Patch Dynamic Model. AB - The distributed patch dissemination strategies are a promising alternative to the conventional centralized patch dissemination strategies. This paper aims to establish a theoretical framework for evaluating the effectiveness of distributed patch dissemination mechanism. Assuming that the Internet offers P2P service for every pair of nodes on the network, a dynamic model capturing both the virus propagation mechanism and the distributed patch dissemination mechanism is proposed. This model takes into account the infected removable storage media and hence captures the interaction of patches with viruses better than the original SIPS model. Surprisingly, the proposed model exhibits much simpler dynamic properties than the original SIPS model. Specifically, our model admits only two potential (viral) equilibria and undergoes a fold bifurcation. The global stabilities of the two equilibria are determined. Consequently, the dynamical properties of the proposed model are fully understood. Furthermore, it is found that reducing the probability per unit time of disconnecting a node from the Internet benefits the containment of electronic viruses. PMID- 26368555 TI - Evaluation of Beef by Electronic Tongue System TS-5000Z: Flavor Assessment, Recognition and Chemical Compositions According to Its Correlation with Flavor. AB - The aim of this study was to assess the ability of electronic tongue system TS 5000Z to evaluate meat quality based on flavor assessment, recognition and correlation with the meat chemical composition. Meat was sampled from eighteen beef cattle including 6 Wagyu breed cattle, 6 Angus breed cattle and 6 Simmental breed cattle. Chemical composition including dry matter, crude protein, fat, ash, cholesterol and taurine and flavor of the meat were measured. The results showed that different breed cattle had different chemical compositions and flavor, which contains sourness, umami, saltiness, bitterness, astringency, aftertaste from astringency, aftertaste from bitterness and aftertaste from umami, respectively. A principal component analysis (PCA) showed an easily visible separation between different breeds of cattle and indicated that TS-5000Z made a rapid identification of different breeds of cattle. In addition, TS-5000Z seemed to be used to predict the chemical composition according to its correlation with the flavor. In conclusion, TS-5000Z would be used as a rapid analytical tool to evaluate the beef quality both qualitatively and quantitatively, based on flavor assessment, recognition and chemical composition according to its correlation with flavor. PMID- 26368557 TI - Estimating Limit Reference Points for Western Pacific Leatherback Turtles (Dermochelys coriacea) in the U.S. West Coast EEZ. AB - Biological limit reference points (LRPs) for fisheries catch represent upper bounds that avoid undesirable population states. LRPs can support consistent management evaluation among species and regions, and can advance ecosystem-based fisheries management. For transboundary species, LRPs prorated by local abundance can inform local management decisions when international coordination is lacking. We estimated LRPs for western Pacific leatherbacks in the U.S. West Coast Exclusive Economic Zone (WCEEZ) using three approaches with different types of information on local abundance. For the current application, the best-informed LRP used a local abundance estimate derived from nest counts, vital rate information, satellite tag data, and fishery observer data, and was calculated with a Potential Biological Removal estimator. Management strategy evaluation was used to set tuning parameters of the LRP estimators to satisfy risk tolerances for falling below population thresholds, and to evaluate sensitivity of population outcomes to bias in key inputs. We estimated local LRPs consistent with three hypothetical management objectives: allowing the population to rebuild to its maximum net productivity level (4.7 turtles per five years), limiting delay of population rebuilding (0.8 turtles per five years), or only preventing further decline (7.7 turtles per five years). These LRPs pertain to all human caused removals and represent the WCEEZ contribution to meeting population management objectives within a broader international cooperative framework. We present multi-year estimates, because at low LRP values, annual assessments are prone to substantial error that can lead to volatile and costly management without providing further conservation benefit. The novel approach and the performance criteria used here are not a direct expression of the "jeopardy" standard of the U.S. Endangered Species Act, but they provide useful assessment information and could help guide international management frameworks. Given the range of abundance data scenarios addressed, LRPs should be estimable for many other areas, populations, and taxa. PMID- 26368558 TI - Mycobacterium tuberculosis Is a Natural Ornithine Aminotransferase (rocD) Mutant and Depends on Rv2323c for Growth on Arginine. AB - Mycobacterium tuberculosis (Mtb) possesses a genetic repertoire for metabolic pathways, which are specific and fit to its intracellular life style. Under in vitro conditions, Mtb is known to use arginine as a nitrogen source, but the metabolic pathways for arginine utilization have not been identified. Here we show that, in the presence of arginine, Mtb upregulates a gene cluster which includes an ornithine aminotransferase (rocD) and Rv2323c, a gene of unknown function. Isotopologue analysis by using 13C- or 15N-arginine revealed that in Mtb arginine is not only used as nitrogen source but also as carbon source for the formation of amino acids, in particular of proline. Surprisingly, rocD, which is widespread in other bacteria and is part of the classical arginase pathway turned out to be naturally deleted in Mtb, but not in non-tuberculous mycobacteria. Mtb lacking Rv2323c showed a growth defect on arginine, did not produce proline from arginine, and incorporated less nitrogen derived from arginine in its core nitrogen metabolism. We conclude that the highly induced pathway for arginine utilization in Mtb differs from that of other bacteria including non-tuberculous mycobacteria, probably reflecting a specific metabolic feature of intracellular Mtb. PMID- 26368559 TI - The Effects of Fetal Gender on Maternal and Fetal Insulin Resistance. AB - OBJECTIVE: Gender plays a role in the development of a number of cardiovascular and metabolic diseases and it has been suggested that females may be more insulin resistant in utero. We sought to assess the relationship between infant gender and insulin resistance in a large pregnancy cohort. STUDY DESIGN: This is a secondary analysis of a cohort from the ROLO randomized control trial of low GI diet in pregnancy. Serum insulin, glucose and leptin were measured in early pregnancy and at 28 weeks. At delivery cord blood C-peptide and leptin were measured. A comparison of maternal factors, fetal biometry, insulin resistance and leptin was made between male and female offspring. A multivariate regression model was built to account for the possible effects of maternal BMI, birthweight and original study group assignment on findings. RESULTS: A total of 582 women were included in this secondary analysis, of whom 304 (52.2%) gave birth to male and 278 (47.8%) gave birth to female infants. Compared to male infants at birth, female infants were significantly lighter, (3945 +/- 436 vs. 4081+/- 549g, p<0.001), shorter in length (52.36 +/- 2.3 vs. 53.05 +/- 2.4cm, p<0.001) and with smaller head circumferences (35.36 +/- 1.5 vs. 36.10 +/- 1.1cm, p<0.001) than males. On multiple regression analysis, women pregnant with female fetuses were less insulin resistant in early pregnancy, i.e. had lower HOMA indices (B = 0.19, p = 0.01). Additionally female fetuses had higher concentrations of both cord blood leptin and C-peptide at birth when compared to male offspring (B = 0.38, p<0.001 and B = 0.31, p = 0.03 respectively). CONCLUSION: These findings suggest gender is a risk factor for insulin resistance in-utero. Additionally, carrying a female fetus decreases the risk of insulin resistance in the mother, from as early as the first trimester. PMID- 26368560 TI - Reference Materials for Calibration of Analytical Biases in Quantification of DNA Methylation. AB - Most contemporary methods for the quantification of DNA methylation employ bisulfite conversion and PCR amplification. However, many reports have indicated that bisulfite-mediated PCR methodologies can result in inaccurate measurements of DNA methylation owing to amplification biases. To calibrate analytical biases in quantification of gene methylation, especially those that arise during PCR, we utilized reference materials that represent exact bisulfite-converted sequences with 0% and 100% methylation status of specific genes. After determining relative quantities using qPCR, pairs of plasmids were gravimetrically mixed to generate working standards with predefined DNA methylation levels at 10% intervals in terms of mole fractions. The working standards were used as controls to optimize the experimental conditions and also as calibration standards in melting-based and sequencing-based analyses of DNA methylation. Use of the reference materials enabled precise characterization and proper calibration of various biases during PCR and subsequent methylation measurement processes, resulting in accurate measurements. PMID- 26368561 TI - Patterns and Drivers of Soil Respiration under Long-Term Citrus reticulate in Southern China. AB - Soil respiration (Rs) is a major source of carbon emission in terrestrial ecosystems. Despite the fact that the influence of land use practice on Rs has been widely studied, the patterns and drivers on Rs of Citrus reticulata cultivation, a worldwide land use practice are unclear. In this current study, we investigated the influence of long-term cultivation of Citrus reticulata (CO) and of CO intercropped with soybean (CB) on soil nutrients, water availability, and Rs in southern China. Results indicated that after 21 years of cultivation, CO and CB significantly increased total soil carbon (TC), total soil nitrogen (TN), and soil organic matter (OM) at 0-20 cm and 20-40 cm, both at upslope and downslope compared with bare soil (CK). However, soil moisture (SM), dissolved organic carbon (DOC), and microbial biomass carbon (MBC) decreased under CB. In addition, no significant variation was found in soil pH between CK, CO, and CB. Across incubation time (56 days), Rs decreased exponentially with incubation time and CB showed the highest Rs rate irrespective of soil depth or topography. Linear regression further showed TC and TN as the two major factors influencing Rs upslope, while DOC was the dominant factor in regulating Rs downslope. These findings demonstrated that long-term cultivation of citrus significantly changed soil nutrients, water availability, and Rs rate. PMID- 26368563 TI - Correction: Cytoprotective Effects of Grape Seed Extract on Human Gingival Fibroblasts in Relation to Its Antioxidant Potential. PMID- 26368562 TI - Adverse Events during Bowel Preparation and Colonoscopy in Patients with Acute Lower Gastrointestinal Bleeding Compared with Elective Non-Gastrointestinal Bleeding. AB - BACKGROUND: There are limited data on the safety of colonoscopy in patients with lower gastrointestinal bleeding (LGIB). We examined the various adverse events associated with colonoscopy in acute LGIB compared with non-GIB patients. METHODS: Emergency hospitalized LGIB patients (n = 161) and age- and gender matched non-GIB controls (n = 161) were selected. Primary outcomes were any adverse events during preparation and colonoscopy procedure. Secondary outcomes were five bowel preparation-related adverse events--hypotension, systolic blood pressure <100 mmHg, volume overload, vomiting, aspiration pneumonia and loss of consciousness--and four colonoscopy-related adverse events--including hypotension, perforation, cerebrocardiovascular events and sepsis. RESULTS: During bowel preparation, 16 (9%) LGIB patients experienced an adverse event. None of the LGIB patients experienced volume overload, aspiration pneumonia or loss of consciousness; however, 12 (7%) had hypotension and 4 (2%) vomited. There were no significant differences in the five bowel preparation-related adverse events between LGIB and non-GIB patients. During colonoscopy, 25 (15%) LGIB patients experienced an adverse event. None LGIB patient had perforation or sepsis; however, 23 (14%) had hypotension and 2 (1%) experienced a cerebrocardiovascular event. There was no significant difference in the four colonoscopy-related adverse events between LGIB and non-GIB patients. In addition, no significant difference in any of the nine adverse events was found among subgroups: patients aged >=65 years, those with comorbidities, and those with antithrombotic drug use. CONCLUSIONS: Adverse events in bowel preparation and colonoscopy among acute LGIB patients were low. No significant difference was found in adverse events between LGIB and non-GIB patients. These adverse events were also low in elderly LGIB patients, as well as in those with co-morbidities and antithrombotic drug use, suggesting that colonoscopy performed during acute LGIB did not increase adverse events. PMID- 26368564 TI - Correction: Cognitive Fatigue Destabilizes Economic Decision Making Preferences and Strategies. PMID- 26368565 TI - The Human Endogenous Protection System against Cell-Free Hemoglobin and Heme Is Overwhelmed in Preeclampsia and Provides Potential Biomarkers and Clinical Indicators. AB - Preeclampsia (PE) complicates 3-8% of all pregnancies and manifests clinically as hypertension and proteinuria in the second half of gestation. The pathogenesis of PE is not fully understood but recent studies have described the involvement of cell-free fetal hemoglobin (HbF). Hypothesizing that PE is associated with prolonged hemolysis we have studied the response of the cell-free Hb- and heme defense network. Thus, we have investigated the levels of cell-free HbF (both free, denoted HbF, and in complex with Hp, denoted Hp-HbF) as well as the major human endogenous Hb- and heme-scavenging systems: haptoglobin (Hp), hemopexin (Hpx), alpha1-microglobulin (A1M) and CD163 in plasma of PE women (n = 98) and women with normal pregnancies (n = 47) at term. A significant increase of the mean plasma HbF concentration was observed in women with PE. Plasma levels of Hp and Hpx were statistically significantly reduced, whereas the level of the extravascular heme- and radical scavenger A1M was significantly increased in plasma of women with PE. The Hpx levels significantly correlated with maternal blood pressure. Furthermore, HbF and the related scavenger proteins displayed a potential to be used as clinical biomarkers for more precise diagnosis of PE and are candidates as predictors of identifying pregnancies with increased risk of obstetrical complications. The results support that PE pathophysiology is associated with increased HbF-concentrations and an activation of the physiological Hb-heme defense systems. PMID- 26368566 TI - Robust Optical Recognition of Cursive Pashto Script Using Scale, Rotation and Location Invariant Approach. AB - The presence of a large number of unique shapes called ligatures in cursive languages, along with variations due to scaling, orientation and location provides one of the most challenging pattern recognition problems. Recognition of the large number of ligatures is often a complicated task in oriental languages such as Pashto, Urdu, Persian and Arabic. Research on cursive script recognition often ignores the fact that scaling, orientation, location and font variations are common in printed cursive text. Therefore, these variations are not included in image databases and in experimental evaluations. This research uncovers challenges faced by Arabic cursive script recognition in a holistic framework by considering Pashto as a test case, because Pashto language has larger alphabet set than Arabic, Persian and Urdu. A database containing 8000 images of 1000 unique ligatures having scaling, orientation and location variations is introduced. In this article, a feature space based on scale invariant feature transform (SIFT) along with a segmentation framework has been proposed for overcoming the above mentioned challenges. The experimental results show a significantly improved performance of proposed scheme over traditional feature extraction techniques such as principal component analysis (PCA). PMID- 26368567 TI - High-Throughput Tissue Bioenergetics Analysis Reveals Identical Metabolic Allometric Scaling for Teleost Hearts and Whole Organisms. AB - Organismal metabolic rate, a fundamental metric in biology, demonstrates an allometric scaling relationship with body size. Fractal-like vascular distribution networks of biological systems are proposed to underlie metabolic rate allometric scaling laws from individual organisms to cells, mitochondria, and enzymes. Tissue-specific metabolic scaling is notably absent from this paradigm. In the current study, metabolic scaling relationships of hearts and brains with body size were examined by improving on a high-throughput whole-organ oxygen consumption rate (OCR) analysis method in five biomedically and environmentally relevant teleost model species. Tissue-specific metabolic scaling was compared with organismal routine metabolism (RMO2), which was measured using whole organismal respirometry. Basal heart OCR and organismal RMO2 scaled identically with body mass in a species-specific fashion across all five species tested. However, organismal maximum metabolic rates (MMO2) and pharmacologically induced maximum cardiac metabolic rates in zebrafish Danio rerio did not show a similar relationship with body mass. Brain metabolic rates did not scale with body size. The identical allometric scaling of heart and organismal metabolic rates with body size suggests that hearts, the power generator of an organism's vascular distribution network, might be crucial in determining teleost metabolic rate scaling under routine conditions. Furthermore, these findings indicate the possibility of measuring heart OCR utilizing the high-throughput approach presented here as a proxy for organismal metabolic rate-a useful metric in characterizing organismal fitness. In addition to heart and brain OCR, the current approach was also used to measure whole liver OCR, partition cardiac mitochondrial bioenergetic parameters using pharmacological agents, and estimate heart and brain glycolytic rates. This high-throughput whole-organ bioenergetic analysis method has important applications in toxicology, evolutionary physiology, and biomedical sciences, particularly in the context of investigating pathogenesis of mitochondrial diseases. PMID- 26368569 TI - A Small Motor Cortex Lesion Abolished Ocular Dominance Plasticity in the Adult Mouse Primary Visual Cortex and Impaired Experience-Dependent Visual Improvements. AB - It was previously shown that a small lesion in the primary somatosensory cortex (S1) prevented both cortical plasticity and sensory learning in the adult mouse visual system: While 3-month-old control mice continued to show ocular dominance (OD) plasticity in their primary visual cortex (V1) after monocular deprivation (MD), age-matched mice with a small photothrombotically induced (PT) stroke lesion in S1, positioned at least 1 mm anterior to the anterior border of V1, no longer expressed OD-plasticity. In addition, in the S1-lesioned mice, neither the experience-dependent increase of the spatial frequency threshold ("visual acuity") nor of the contrast threshold ("contrast sensitivity") of the optomotor reflex through the open eye was present. To assess whether these plasticity impairments can also occur if a lesion is placed more distant from V1, we tested the effect of a PT-lesion in the secondary motor cortex (M2). We observed that mice with a small M2-lesion restricted to the superficial cortical layers no longer expressed an OD-shift towards the open eye after 7 days of MD in V1 of the lesioned hemisphere. Consistent with previous findings about the consequences of an S1-lesion, OD-plasticity in V1 of the nonlesioned hemisphere of the M2 lesioned mice was still present. In addition, the experience-dependent improvements of both visual acuity and contrast sensitivity of the open eye were severely reduced. In contrast, sham-lesioned mice displayed both an OD-shift and improvements of visual capabilities of their open eye. To summarize, our data indicate that even a very small lesion restricted to the superficial cortical layers and more than 3mm anterior to the anterior border of V1 compromised V1 plasticity and impaired learning-induced visual improvements in adult mice. Thus both plasticity phenomena cannot only depend on modality-specific and local nerve cell networks but are clearly influenced by long-range interactions even from distant brain regions. PMID- 26368568 TI - Epidemiology of Leptospirosis in Africa: A Systematic Review of a Neglected Zoonosis and a Paradigm for 'One Health' in Africa. AB - BACKGROUND: Leptospirosis is an important but neglected bacterial zoonosis that has been largely overlooked in Africa. In this systematic review, we aimed to summarise and compare current knowledge of: (1) the geographic distribution, prevalence, incidence and diversity of acute human leptospirosis in Africa; and (2) the geographic distribution, host range, prevalence and diversity of Leptospira spp. infection in animal hosts in Africa. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, we searched for studies that described (1) acute human leptospirosis and (2) pathogenic Leptospira spp. infection in animals. We performed a literature search using eight international and regional databases for English and non-English articles published between January 1930 to October 2014 that met out pre-defined inclusion criteria and strict case definitions. RESULTS AND DISCUSSION: We identified 97 studies that described acute human leptospirosis (n = 46) or animal Leptospira infection (n = 51) in 26 African countries. The prevalence of acute human leptospirosis ranged from 2 3% to 19 8% (n = 11) in hospital patients with febrile illness. Incidence estimates were largely restricted to the Indian Ocean islands (3 to 101 cases per 100,000 per year (n = 6)). Data from Tanzania indicate that human disease incidence is also high in mainland Africa (75 to 102 cases per 100,000 per year). Three major species (Leptospira borgpetersenii, L. interrogans and L. kirschneri) are predominant in reports from Africa and isolates from a diverse range of serogroups have been reported in human and animal infections. Cattle appear to be important hosts of a large number of Leptospira serogroups in Africa, but few data are available to allow comparison of Leptospira infection in linked human and animal populations. We advocate a 'One Health' approach to promote multidisciplinary research efforts to improve understanding of the animal to human transmission of leptospirosis on the African continent. PMID- 26368570 TI - The Complex Pre-Execution Stage of Auditory Cognitive Control: ERPs Evidence from Stroop Tasks. AB - Cognitive control has been extensively studied from Event-Related Potential (ERP) point of view in visual modality using Stroop paradigms. Little work has been done in auditory Stroop paradigms, and inconsistent conclusions have been reported, especially on the conflict detection stage of cognitive control. This study investigated the early ERP components in an auditory Stroop paradigm, during which participants were asked to identify the volume of spoken words and ignore the word meanings. A series of significant ERP components were revealed that distinguished incongruent and congruent trials: two declined negative polarity waves (the N1 and the N2) and three declined positive polarity wave (the P1, the P2 and the P3) over the fronto-central area for the incongruent trials. These early ERP components imply that both a perceptual stage and an identification stage exist in the auditory Stroop effect. A 3-stage cognitive control model was thus proposed for a more detailed description of the human cognitive control mechanism in the auditory Stroop tasks. PMID- 26368571 TI - Evolution of the Antisense Overlap between Genes for Thyroid Hormone Receptor and Rev-erbalpha and Characterization of an Exonic G-Rich Element That Regulates Splicing of TRalpha2 mRNA. AB - The alpha-thyroid hormone receptor gene (TRalpha) codes for two functionally distinct proteins: TRalpha1, the alpha-thyroid hormone receptor; and TRalpha2, a non-hormone-binding variant. The final exon of TRalpha2 mRNA overlaps the 3' end of Rev-erbalpha mRNA, which encodes another nuclear receptor on the opposite strand of DNA. To understand the evolution of this antisense overlap, we sequenced these genes and mRNAs in the platypus Orthorhynchus anatinus. Despite its strong homology with other mammals, the platypus TRalpha/Rev-erbalpha locus lacks elements essential for expression of TRalpha2. Comparative analysis suggests that alternative splicing of TRalpha2 mRNA expression evolved in a stepwise fashion before the divergence of eutherian and marsupial mammals. A short G-rich element (G30) located downstream of the alternative 3'splice site of TRalpha2 mRNA and antisense to the 3'UTR of Rev-erbalpha plays an important role in regulating TRalpha2 splicing. G30 is tightly conserved in eutherian mammals, but is absent in marsupials and monotremes. Systematic deletions and substitutions within G30 have dramatically different effects on TRalpha2 splicing, leading to either its inhibition or its enhancement. Mutations that disrupt one or more clusters of G residues enhance splicing two- to three-fold. These results suggest the G30 sequence can adopt a highly structured conformation, possibly a G-quadruplex, and that it is part of a complex splicing regulatory element which exerts both positive and negative effects on TRalpha2 expression. Since mutations that strongly enhance splicing in vivo have no effect on splicing in vitro, it is likely that the regulatory role of G30 is mediated through linkage of transcription and splicing. PMID- 26368572 TI - Comparing the Health Care Experiences of Medicare Beneficiaries with and without Depressive Symptoms in Medicare Managed Care versus Fee-for-Service. AB - OBJECTIVE: To compare patient experiences and disparities for older adults with depressive symptoms in managed care (Medicare Advantage [MA]) versus Medicare Fee for-Service (FFS). DATA SOURCES: Data came from the 2010 Medicare CAHPS survey, to which 220,040 MA and 135,874 FFS enrollees aged 65 and older responded. STUDY DESIGN: Multivariate linear regression was used to test whether case-mix-adjusted associations between depressive symptoms and patient experience differed for beneficiaries in MA versus FFS. Dependent measures included four measures of beneficiaries' experiences with doctors (e.g., reports of doctor communication) and seven measures of beneficiaries' experiences with plans (e.g., customer service). PRINCIPAL FINDINGS: Beneficiaries with depressive symptoms reported worse experiences than those without depressive symptoms regardless of coverage type. For measures assessing interactions with the plan (but not for measures assessing interactions with doctors), the disadvantage for beneficiaries with versus without depressive symptoms was larger in MA than in FFS. CONCLUSIONS: Disparities in care experienced by older Medicare beneficiaries with depressive symptoms tend to be more negative in managed care than in FFS. Efforts are needed to identify and address the barriers these beneficiaries encounter to help them better traverse the managed care environment. PMID- 26368575 TI - Alterations in lipid peroxidation and T-cell function in women with hyperemesis gravidarum. AB - The objective of this study was to investigate serum adenosine deaminase (ADA) activity as a marker of T lymphocyte activation and parameters of oxidative stress and antioxidant defence in hyperemesis gravidarum (HG). Serum ADA activity, malondialdehyde (MDA), catalase (CAT) and glutathione peroxidase (GPx) levels were investigated in 40 pregnant women with the HG and 40 with healthy pregnancies, in a descriptive study. Although serum ADA and CAT were measured to be higher in HG group, the difference was not significant. Serum MDA and GPx levels were significantly elevated in women with HG when compared with those without HG. The significance of changes in lipid peroxidation and T-cell activation in the pathogenesis of HG and whether this is a cause or a compensatory reaction to HG requires further investigations with larger multicentre trials. PMID- 26368574 TI - An 8-Year Prospective Study of Depressive Symptoms and Change in Insulin From Adolescence to Young Adulthood. AB - OBJECTIVE: To evaluate whether depressive symptoms predict change in fasting insulin among adolescents followed into young adulthood. We hypothesized that higher depressive symptoms would predict increased insulin and that puberty and race/ethnicity would moderate this relationship. METHODS: Data came from the Princeton School District Study, a school-based longitudinal cohort of non Hispanic black and white adolescents (2001-2011). Depressive symptoms, fasting insulin, and body mass index were measured at baseline (adolescence) and 8 years later (young adulthood) in 685 participants. Puberty was assessed using a validated protocol measuring sex steroids and physical changes. The primary outcome was change in fasting insulin. Analyses accounted for age, sex, race, parental education, baseline insulin, body mass index z score, puberty, and time to follow-up. RESULTS: At baseline, depressive symptoms were correlated with insulin (rho = 0.13, p = .001). High baseline insulin predicted insulin change (B = -11.50, standard error [SE] = 2.30, p < .001). Depressive symptoms also predicted insulin change, but only for pubertal adolescents (B = -0.23, SE = 0.11, p = .038). This relationship was moderated by race (p = .047); depressive symptoms predicted insulin change only among pubertal black adolescents (p = .030), not white (p = .49), and in the direction opposite that hypothesized (Bblacks = -0.51, SE = 0.23). Post hoc analyses revealed that pubertal black adolescents with high depressive symptoms had the highest baseline insulin, which stayed high across the follow-up period. CONCLUSIONS: Among pubertal black adolescents, elevated depressive symptoms are associated with increased risk for sustained hyperinsulinemia from adolescence into adulthood. These youths may be particularly vulnerable for Type 2 diabetes. PMID- 26368573 TI - Integrative Model of Oxidative Stress Adaptation in the Fungal Pathogen Candida albicans. AB - The major fungal pathogen of humans, Candida albicans, mounts robust responses to oxidative stress that are critical for its virulence. These responses counteract the reactive oxygen species (ROS) that are generated by host immune cells in an attempt to kill the invading fungus. Knowledge of the dynamical processes that instigate C. albicans oxidative stress responses is required for a proper understanding of fungus-host interactions. Therefore, we have adopted an interdisciplinary approach to explore the dynamical responses of C. albicans to hydrogen peroxide (H2O2). Our deterministic mathematical model integrates two major oxidative stress signalling pathways (Cap1 and Hog1 pathways) with the three major antioxidant systems (catalase, glutathione and thioredoxin systems) and the pentose phosphate pathway, which provides reducing equivalents required for oxidative stress adaptation. The model encapsulates existing knowledge of these systems with new genomic, proteomic, transcriptomic, molecular and cellular datasets. Our integrative approach predicts the existence of alternative states for the key regulators Cap1 and Hog1, thereby suggesting novel regulatory behaviours during oxidative stress. The model reproduces both existing and new experimental observations under a variety of scenarios. Time- and dose-dependent predictions of the oxidative stress responses for both wild type and mutant cells have highlighted the different temporal contributions of the various antioxidant systems during oxidative stress adaptation, indicating that catalase plays a critical role immediately following stress imposition. This is the first model to encapsulate the dynamics of the transcriptional response alongside the redox kinetics of the major antioxidant systems during H2O2 stress in C. albicans. PMID- 26368576 TI - Chemically synthesized dicarba H2 relaxin analogues retain strong RXFP1 receptor activity but show an unexpected loss of in vitro serum stability. AB - Peptides and proteins are now acknowledged as viable alternatives to small molecules as potential therapeutic agents. A primary limitation to their more widespread acceptance is their generally short in vivo half-lives due to serum enzyme susceptibility and rapid renal clearance. Numerous chemical approaches to address this concern have been undertaken in recent years. The replacement of disulfide bonds with non-reducible elements has been demonstrated to be one effective means by eliminating the deleterious effect of serum reductases. In particular, substitution with dicarba bonds via ring closure metathesis has been increasingly applied to many bioactive cystine-rich peptides. We used this approach for the replacement of the A-chain intramolecular disulfide bond of human relaxin 2 (H2 relaxin), an insulin-like peptide that has important regulatory roles in cardiovascular and connective tissue homeostasis that has led to successful Phase IIIa clinical trials for the treatment of acute heart failure. Use of efficient solid phase synthesis of the two peptide chains was followed by on-resin ring closure metathesis and formation of the dicarba bond within the A-chain and then by off-resin combination with the B-chain via sequential directed inter-chain disulfide bond formation. After purification and comprehensive chemical characterization, the two isomeric synthetic H2 relaxin analogues were shown to retain near-equipotent RXFP1 receptor binding and activation propensity. Unexpectedly, the in vitro serum stability of the analogues was greatly reduced compared with the native peptide. Circular dichroism spectroscopy studies showed subtle differences in the secondary structures between dicarba analogues and H2 relaxin suggesting that, although the overall fold is retained, it may be destabilized which could account for rapid degradation of dicarba analogues in serum. Caution is therefore recommended when using ring closure metathesis as a general approach to enhance peptide stability. PMID- 26368578 TI - The use of Pierre Bourdieu's distinction concepts in scientific articles studying food and eating: A narrative review. AB - This article reviews and discusses scientific papers on eating practices that have used Pierre Bourdieu's concepts presented in Distinction: A Social Critique of the Judgement of Taste. It aims to synthesize and analyze theoretical and empirical studies on the theme in order to present Bourdieu's contributions to the field, advances in his theories, and directions for future research. Exclusion criteria were: not written in Portuguese, English, Spanish, or French; not published in a peer-reviewed journal; not analyzing food or eating; and not using Bourdieu's concepts as presented in Distinction as the main theoretical framework. In this narrative review, we found 38 articles, which were categorized main themes: food choice and provisioning, taste, social class, food symbolism, the body, and the scientific field of food and eating. The taste of luxury and the taste of necessity were broadly applied on the works found in this review and were observed among the lower and upper classes, manifesting differently in each class. These studies show that while Bourdieu's theories are still highly relevant to understanding contemporary social groups, they may be improved when combined with other frameworks and theorists. We highlight as directions for future research manners in which gender and the environment interact with the habitus and food choices. Finally, this review points to new areas of investigation that may help improve the use of Bourdieu's concepts in exploring health inequalities, such as differences in eating practices and habitus within populations with low socioeconomic status. PMID- 26368577 TI - Environmental influences on small eating behavior change to promote weight loss among Black and Hispanic populations. AB - Small eating behavior changes are proposed as more feasible to achieve and maintain than larger changes used in traditional behavioral weight loss studies. However, it is unclear whether overweight Black and Hispanic adults in a low income urban setting experience small changes as feasible and what might influence feasibility. Participants' experiences in a 12-week pilot weight loss intervention were explored qualitatively to determine the feasibility of making small eating behavior changes in this population. After the intervention (69% retention), semi-structured interviews with 46 men and women (mean age 51, 50% Non-Hispanic Black, 43% Hispanic) revealed that making small eating changes was a process shaped by participants' intrapersonal and interpersonal eating environments. Participants responded to intrapersonal and interpersonal eating environmental challenges by adapting small change strategies, navigating eating environments, and negotiating household eating practices. Findings highlight how even small eating behavior changes called for adaptation, navigation, and negotiation of complex eating environments in daily life. These findings were used to improve the trial that followed and underline the importance of feasibility studies to inform community trials. Findings also add to understanding of contextual challenges and the skills needed to implement small changes in a low income, ethnic minority population. PMID- 26368579 TI - Confronting the meat paradox in different cultural contexts: Reactions among Chinese and French participants. AB - As a well-known source of nutrition and pleasure, meat plays an important role in most people's diet. However, awareness of the "meat paradox"-the association of liking to eat meat but not wanting to kill animals-often implies the experience of cognitive dissonance. In two studies, focusing on meat production and meat consumption respectively, we examined whether participants used reduction of willingness to eat meat and reduction of mind attribution to food animals as strategies to reduce cognitive dissonance from the meat paradox in the Chinese and French cultural contexts. Focusing on meat production (slaughtering of an animal to produce meat; Study 1, n = 520), participants reported lower willingness to eat beef in a condition that emphasized the slaughter of a cow compared to a condition that presented a diagram of a cow as meat. In addition, French but not Chinese participants attributed less mind to cows when the relation between meat and its animal origin was made salient. Focusing on meat consumption (the transformation of meat into food; Study 2, n = 518), participants reported lower willingness to eat beef and attributed less mind to cows in a condition that emphasized the animal origin of meat compared to a condition that presented a recipe. These results suggest that the use of different strategies to resolve cognitive dissonance from the meat paradox depends on different contexts of the meat-animal link as well as on cultural context. PMID- 26368581 TI - Understanding the World of Managed Care: Opportunities and Obstacles for Rehabilitation Teams. AB - Rehabilitation services were not included in the early drive to reduce costs by prospective payment to hospitals for diagnostic related groups (DRGs) of disease or condition. The idea that a hospital could restrict some services and realize a profit on the prospective fee or be sadly underpaid if a patient stay was particularly costly was new in the 1970s. This early form of managed care was designed to curb skyrocketing health care costs. It was not until the late 1980s that managed care for elderly and disabled persons through some Medicare expenditure experiments came about. Still, rehabilitation services were not included. Stroke survivors receive a large portion of their care in rehabilitation services, both in institutions and in the community. This article presents a simple view of managed care, its opportunities and obstacles, with special reference to the impact it can have on the care of stroke survivors in the future. The end purpose is to engage rehabilitation providers in a needed advocacy for the development of sound managed care practices for stroke survivors. PMID- 26368580 TI - Interaction of Polyelectrolytes with Salivary Pellicles on Hydroxyapatite Surfaces under Erosive Acidic Conditions. AB - The modification of acidic beverage formulations with food-approved, nonhazardous substances with antierosive properties has been identified as a key strategy for counteracting the prevalence of dental erosion, i.e., the acid-induced dissolution of hydroxyapatite (HA, the main mineral component of tooth surfaces). While many of such substances have been reported, very little is known on how they interact with teeth and inhibit their acid-induced dissolution. With the aim of filling this gap in knowledge, we have studied under acidic conditions the interaction between two polyelectrolytes of differing ionic character, carboxymethyl cellulose (CMC) and chitosan, and saliva-coated hydroxyapatite, i.e., a model for the outer surface of teeth. These studies were performed by means of ellipsometry, quartz crystal microbalance with dissipation monitoring, and atomic force microscopy. We also studied, by means of pH variations, how dissolution of saliva-coated HA is affected by including these polyelectrolytes in the erosive solutions. Our results confirm that salivary films protect HA from acid-induced dissolution, but only for a limited time. If the acid is modified with CMC, this polyelectrolyte incorporates into the salivary films prolonging in time their protective function. Eventually, the CMC-modified salivary films are removed from the HA surfaces. From this moment, HA is continuously coated with CMC, but this offers only a weak protection against erosion. When the acid is modified with the cationic chitosan, the polyelectrolyte adsorbs on top of the salivary films. Chitosan-modified salivary films are also eventually replaced by bare chitosan films. In this case both coatings offer a similar protection against HA dissolution, which is nevertheless notably higher than that offered by CMC. PMID- 26368582 TI - Managed Care: Effects on Home Health Care Providers and Stroke Survivors. AB - The advent of managed care has changed the delivery of home health care services for stroke survivors and their families. Because clinicians are providing fewer visits, they need to focus their assessment and diagnoses, interventions, and evaluation steps to offer the most effective, efficient, and economic care possible. PMID- 26368583 TI - Managed Care in Rural Health: The Stroke Survivor on Horseback. AB - Managed care has been slow to come to underserved rural areas, where profits may not be as large as in metropolitan areas. In the last decade, increased threat of takeover by out-of-state managed care organizations (MCOs) has prompted rural community hospitals and providers to develop some new models of managed care that fit both their economic and health care needs. Stroke survivors in rural areas have the same need for coordinated, ongoing care during their lifetime, but it is more difficult to deliver it in rural areas. Rehabilitation providers are urged to be proactive in creating innovative managed care approaches that will improve both the health and recovery outcomes of rural stroke survivors. PMID- 26368584 TI - The Role of Medical Conditions and Depression in the Functional Outcome of Stroke Survivors: A Review and Pilot Study. AB - This study is a secondary analysis conducted to describe the population of medically ill people who have had a stroke in terms of functional outcome over time. Functional outcome did not differ between stroke survivors with medical illness and those without medical illness at the two time periods studied. However, there was a difference in functional outcome over time between stroke survivors with medical illness who were depressed and those who were not. PMID- 26368585 TI - Rural Stroke Caregivers: A Qualitative Study of the Positive and Negative Response to the Caregiver Role. AB - Caregivers are often referred to as the "hidden patients." Rarely has caregiving research focused on the positive aspects of caregiving. The purpose of this study was to investigate the lived experiences of caregivers of stroke survivors who have been in the caregiver role for at least 6 months poststroke. The conceptual framework was based on a combination of Lazarus' stress and coping theory and Weiner's attribution theory. A qualitative cross-sectional design was employed. It involved a sample of 10 caregivers from a rural county in Wyoming. A total of 24 categories were identified and five themes emerged: (1) a sense of loyalty; (2) acceptance; (3) a sense of "feeling good"; (4) satisfaction is associated with helping others; and (5) burden is associated with lifestyle change. Participants in this study reported several positive outcomes as well as some negative outcomes in regard to their role as caregivers. PMID- 26368586 TI - The Impact of Interventions with Families Poststroke: A Review. PMID- 26368587 TI - Creating Safer and More Usable Kitchens. PMID- 26368588 TI - Doing the Right Thing: Consequences for Health Care Team Members. PMID- 26368591 TI - Current management of heparin-induced thrombocytopenia. AB - Heparin-induced thrombocytopenia (HIT) is an immune adverse reaction to heparin (both unfractionated and low-molecular-weight), which is mediated by the formation of IgG antibodies against platelet factor 4-heparin complexes. The IgG/platelet factor 4 immunocomplexes activate platelets with resulting thrombocytopenia, which is not associated with bleeding, but with paradoxical life-threatening thrombotic complications, for coagulation activation. HIT diagnosis requires the assessment of pre-test clinical probability in combination with the measurement of platelet activating antibodies against platelet factor 4 heparin complexes with immunological and functional assays. When HIT is diagnosed, any form of heparin should be stopped and a non-heparin alternative anticoagulant should be started. Argatroban and danaparoid are currently the only drugs licensed for HIT, with different country availability. Bivalirudin is an option in cardiac surgery and procedures in HIT patients. PMID- 26368589 TI - Synergistic, collaterally sensitive beta-lactam combinations suppress resistance in MRSA. AB - Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most prevalent multidrug-resistant pathogens worldwide, exhibiting increasing resistance to the latest antibiotic therapies. Here we show that the triple beta-lactam combination meropenem-piperacillin-tazobactam (ME/PI/TZ) acts synergistically and is bactericidal against MRSA subspecies N315 and 72 other clinical MRSA isolates in vitro and clears MRSA N315 infection in a mouse model. ME/PI/TZ suppresses evolution of resistance in MRSA via reciprocal collateral sensitivity of its constituents. We demonstrate that these activities also extend to other carbapenem-penicillin-beta-lactamase inhibitor combinations. ME/PI/TZ circumvents the tight regulation of the mec and bla operons in MRSA, the basis for inducible resistance to beta-lactam antibiotics. Furthermore, ME/PI/TZ subverts the function of penicillin-binding protein-2a (PBP2a) via allostery, which we propose as the mechanism for both synergy and collateral sensitivity. Showing in vivo activity similar to that of linezolid, ME/PI/TZ demonstrates that combinations of older beta-lactam antibiotics could be effective against MRSA infections in humans. PMID- 26368592 TI - Multicomponent Crystal Systems of Known Antimalarial Drug Molecules. AB - Potential drug molecules are often discarded due to poor physicochemical properties and pharmacokinetic profiles. As such, research into the use of multicomponent crystal systems (such as salts and co-crystals) is currently being conducted with the aim of improving the properties of the molecule, without altering the bioactivity of the drug. Although numerous studies have been performed on a wide variety of drug molecules, research with antimalarial drug molecules seems to have been neglected. With many of the current drugs becoming inactive due to resistance, there is an urgent need to find effective drugs with good pharmacokinetic profiles. The objective of this review is therefore to determine the extent to which multicomponent crystal systems have been used in antimalarial chemotherapy and whether this method provides a viable alternative to discarding potential drug candidates. PMID- 26368590 TI - Suppressors of superoxide production from mitochondrial complex III. AB - Mitochondrial electron transport drives ATP synthesis but also generates reactive oxygen species, which are both cellular signals and damaging oxidants. Superoxide production by respiratory complex III is implicated in diverse signaling events and pathologies, but its role remains controversial. Using high-throughput screening, we identified compounds that selectively eliminate superoxide production by complex III without altering oxidative phosphorylation; they modulate retrograde signaling including cellular responses to hypoxic and oxidative stress. PMID- 26368593 TI - Reentrant Stabilization of Grafted Nanoparticles in Polymer Solutions. AB - Polymer chains grafted onto nanoparticles may facilitate the dispersion of such particles in a polymer solution. We explore the optimal strategy for stabilizing polymer-grafted nanoparticles using self-consistent field theory and experiments. The best results are obtained for relatively low grafting densities and for chain lengths of the brush polymer NB larger than that of the freely floating polymers Nf. When Nf > NB, one finds a compatibilization gap and re-entrant stabilization: At both very low and very high polymer concentrations particles disperse in the polymer solution, while at intermediate concentrations the particles lose their colloidal stability. At low grafting densities the underlying surface is in contact with the solvent. Particles covered by a bidisperse brush can combine a low grafting outer region with full coverage of the surface by a densely grafted inner layer. Using classical colloid-chemical stabilization criteria the region in the phase diagram for which the particles are expected to mix with a concentrated polymer solution opens up. Now, also upon an increase in the length of the freely dispersed polymers, a re-entrant colloid-chemical stabilization is found for particles on the nanometer length scale: At both short and long polymer chains in solution the particles will not aggregate, whereas at intermediate lengths the colloidal stability is marginal. This multi re-entrant behavior is found from numerical self-consistent field calculations, and these predictions are consistent with corresponding experiments. PMID- 26368594 TI - Synthesis of a Neo-Confused Octaphyrin and the Formation of Its Mononuclear Complexes. AB - Novel neo-confused octaphyrin(1.1.1.1.1.1.1.0) (1) was synthesized by oxidative ring closure of an octapyrrane bearing two terminal "confused" pyrroles. Crystal structures of its Zn(II) and Cu(II) complexes (2 and 3) show a figure-of-eight conformation with unique mononuclear coordination structures. Photophysical data and theoretical calculations suggest that the neo-confused octaphyrin 1 is a 34pi electron conjugated species showing nonaromaticity. Coordination of copper and zinc ions results in the further narrowing of the HOMO-LUMO gaps. PMID- 26368595 TI - Particle Paradigms. PMID- 26368596 TI - From Coal Mine Dust To Quartz: Mechanisms of Pulmonary Pathogenicity. AB - Exposure to coal mine dust or crystalline silica can result in the initiation and progression of interstitial lung disease. Pathogenesis is the consequence of damage to lung cells and resulting lung scarring associated with activation of fibrotic processes. This review presents the radiologic and histologic characteristics of simple and complicated coal workers' pneumoconiosis (CWP) as well as pathological indices of acute and chronic silicosis. This presentation also reviews the results of in vitro, animal, and human investigations that elucidate mechanisms involved in the development of these pneumoconioses. Results support the involvement of four basic mechanisms in the etiology of CWP and silicosis: 1. Direct cytotoxicity of coal dust or silica, resulting in lung cell damage, release of lipases and proteases, and eventual lung scarring. 2. Activation of oxidant production by pulmonary phagocytes, such as alveolar macrophages. When oxidant production exceeds antioxidant defenses, lipid peroxidation and protein nitrosation occur, resulting in tissue injury and consequent scarring. 3. Activation of mediator release from alveolar macrophages and alveolar epithelial cells. Chemokines recruit polymorphonuclear leukocytes and macrophages from the pulmonary capillaries into the air spaces. Once within the air spaces, these leukocytes are activated by proinflammatory cytokines to produce reactive species, which increase oxidant injury and lung scarring. 4. Secretion of growth factors from alveolar macrophages and alveolar epithelial cells. Release of such mediators stimulates fibroblast proliferation and induces fibrosis. In conclusion, results of in vitro and animal studies have provided the basis for proposing mechanisms that may lead to the initiation and progression of CWP and silicosis. Data obtained from exposed workers has lent support to these proposals. The mechanistic understanding obtained for the development of CWP and silicosis should be useful in elucidating the possible pathogenicity of other inhaled particles. PMID- 26368597 TI - Pathogenesis of Fibrosis Produced by Asbestos and Man-Made Mineral Fibers: What Makes a Fiber Fibrogenic? AB - Recent studies have revealed a wide array of molecular and cellular changes in cells and whole lungs exposed to asbestos fibers, changes that are presumed to be related to asbestos-induced fibrogenesis. These include generation of reactive oxygen species (ROS), induction of cell signaling factors and proinflammatory cytokines, and induction of fibrogenic mediators. Tumor necrosis factor-alpha (TNFalpha) appears to play a crucial role, since mice with TNFalpha receptor genes knocked out are resistant to asbestos-induced fibrosis. However, many man made mineral fibers (MMVF) are able to generate ROS, cell signaling factors, and proinflammatory cytokines (probably every fiber causes expression of TNFalpha), but there is no clear correlation between the ability of MMVF to initiate these events and their ability to produce fibrosis. Moreover, asbestos produces fibrosis in tracheal explant systems without increasing TNFalpha expression, and nonfibrogenic dusts induce fibrogenic mediators such as transforming growth factor-beta (TCFbeta) and platelet-derived growth factor (PDGF) but not procollagen in such systems. It remains uncertain whether alveolar macrophages are central to fibrosis, as is often assumed, or whether fibers penetrating tissue are the real effector agents. Fiber length, biopersistence, and dose clearly do play a very important role in fibrogenesis, since short fibers, readily degraded fibers, and small numbers of fibers of any type are nonfibrogenic. There is some evidence to suggest that short and nonpersistent fibers produce quantitatively less of the mediators just described, but the ability of macrophages to clear fibers is probably crucial to preventing fibrosis. Thus, molecular and cellular events must combine in as yet uncertain ways with abnormalities at a more "'macroscopic" level before fibrosis can become established. PMID- 26368598 TI - Organic Dusts: Beyond Endotoxin. AB - Organic dust is defined as dust that originates from plant or animal matter. Organic-dust-associated respiratory effects can potentially be due to many different constituents of the dust. Endotoxins, from gram-negative bacteria, have for a long time been considered as important nonimmunogenic, nonallergenic inflammatory constituents responsible for systemic and respiratory effects in a wide range of agricultural industries. Other constituents with a similar mode of action have been identified, such as beta(1->3)-glucans from molds and peptidoglycans predominantly from gram-positive bacteria, although their toxicology and epidemiology are still to be established. At the same time, exposures to these agents other than in occupational settings, such as in indoor and outdoor exposures, are being evaluated for their potential effects on humans. PMID- 26368599 TI - Particulate Matter and Cardiopulmonary Health: A Perspective. AB - The epidemiological evidence for PM-associated health effects continues to mount. The effects, including morbidity and mortality, are most evident in the elderly and those with preexisting impairments in cardiopulmonary health. Recent preliminary field and controlled clinical studies support these associations by suggesting that PM can alter cardiac risk factors in a manner consistent with a higher risk of second heart attack. Empirical studies in healthy animals have provided evidence that PM and its emission surrogates cause lung injury, and perhaps more importantly, these PM can exaggerate inflammatory, biochemical, hematologic, and physiologic impairments in animal models of cardiopulmonary disease. These findings have brought attention to the often underappreciated, integral structural and physiological interplay of the heart and lungs within the cardiopulmonary system, especially in conventional inhalation toxicology studies. If animal models are to enhance our understanding of PM health effects in humans, it is critical that we expand our knowledge of this interplay in both humans and animal models when the lung is challenged with PM or its copollutants. How PM modulates autonomic and other homeostatic functions of the cardiopulmonary system, particularly in those with preexisting impairments or heart-lung disease, will enhance our understanding of public health risks and the likely multiplicity of factors that determine the responsiveness of any individual. PMID- 26368600 TI - Particulate Matter Physicochemistry and Toxicology: In Search of Causality-A Critical Perspective. AB - Results from epidemiology studies have shown statistical associations between ambient air particulate matter (PM) concentrations and mortality/morbidity, particularly among susceptible subpopulations. Although the epidemiology of ambient air PM is compelling, there remains considerable uncertainty in PM risk assessment, particularly with regard to identification of PM properties and mechanisms that are responsible for its observed adverse health effects. In addition, the biological mechanisms by which specific PM properties mediate their adverse health effects are currently not known. In vivo and in vitro toxicological studies have examined particles derived from a number of sources such as ambient air, combustion, and natural sources, as well as laboratory derived surrogate particles, in order to identify the characteristics of particles that are responsible for their adverse health effects. These studies have identified a number of potential causal biogenic, physical, and chemical properties of PM. A number of PM physical and chemical properties have been found to elicit biological responses in animal models of disease, which has enhanced their plausibility as being properties responsible for PM-associated health effects. In vitro mechanistic studies have shown that PM derived from a variety of sources mediate their adverse biological effects by inducing an oxidative stress, which may alter intracellular signal transduction pathways that regulate a number of biological responses such as cell growth, stress response, apoptosis, and inflammation. The challenge of future PM toxicology research will be to demonstrate "biological plausibility and coherence" for potential causal PM properties. PMID- 26368601 TI - Functional Genomics of Particle-Induced Lung Injury. AB - Currently, the biological mechanisms controlling adverse reactions to particulate matter are uncertain, but are likely to include oxidative lung injury, inflammation, infection, and preexisting pulmonary disease (e.g., chronic obstructive pulmonary diseaseJ. Each mechanism can be viewed as a complex trait controlled by interactions of host (genetic) and environmental factors. We propose that genetic factors play a major role in susceptibility to particulate matter because the number of individuals exposed (even in occupational settings) is often large, but relatively few people respond with increases in morbidity and even mortality. Previous clinical studies support this hypothesis, having discovered marked individual variation in diminished lung function following oxidant exposures. Advances in functional genomics have facilitated the examination of this hypothesis and have begun to provide valuable new insights into gene-environmental interactions. For example, genome-wide scans can be completed readily in mice that enable assessment of chromosomal regions with linkage to quantitative traits. Recently, we and others have identified linkage to oxidant-induced inflammation and mortality. Such linkage analysis can narrow and prioritize candidate gene(s) for further investigation, which, in turn, is aided by existing transgenic mouse models. In addition, differential expression (microarray) analysis enables simultaneous assessment of thousands of genes and expressed sequence tags. Combining genome-wide scan with microarray analysis permits a comprehensive assessment of adverse responses to environmental stimuli and will lead to progress in understanding the complex cellular mechanisms and genetic determinants of susceptibility to particulate matter. PMID- 26368602 TI - Role of Iron in the Cellular Effects of Asbestos. AB - Research to understand how the physical characteristics of asbestos fibers impact the pathological effects has intensified in the past 10 years. The role that iron, intrinsic or acquired, may play has been the subject of many of these investigations. Asbestos catalyzes many of the same reactions that iron does, including lipid peroxidation and DNA damage. At physiological pH, mobilization of iron from the fibers by a low-molecular-weight chelator greatly enhances these reactions. Iron is also mobilized from asbestos fibers in human lung epithelial (A549) cells after the fibers are endocytized. The iron appears to move from a low-molecular-weight pool to nonferritin proteins and ferritin. The amount of iron in the low-molecular-weight pool was directly correlated with the toxicity of the asbestos. Glutathione (CSH) levels in these cells were dramatically reduced after asbestos treatment as a result of CSH efflux. This was not related to the iron associated with the fibers, but appeared to be due in some way to the silicate structure. The presence of the mobilized iron in the cells depleted of CSH creates a very oxidizing environment. Asbestos treatment of cells resulted in DNA oxidation, as assessed by formation of 8-hydroxy-2'-deoxyguanosine (8-oxo dCJ. The DNA oxidation was dependent upon the iron associated with the fibers and the enzymatic generation of (*) NO by the cells. The induction of the inducible form of nitric oxide synthase (iNOS), responsible for the production of "NO, was dependent upon the presence of iron from the fibers and the decrease in CSH. One without the other did not lead to induction of iNOS. Asbestos was mutagenic in hgprt-gpt(+) V79 Chinese hamster lung cells. The mutagenicity was dependent upon iron, intrinsic or acquired. Addition of (*) NO synergistically increased the mutagenicity of the asbestos, suggesting that in cells that respond to asbestos by making (*) NO, the response will be enhanced. This also suggests that the responses will be enhanced in the presence of activated macrophages producing (*) NO or in the presence of cigarette smoke, because of the presence of (*) NO and iron chelators in the smoke. PMID- 26368603 TI - Effect of Micromorphology and Surface Reactivity of Several Unusual forms of Crystalline Silica on the toxicity to a Monocyte-Macrophage Tumor Cell Line. AB - The fibrogenic or carcinogenic response to the inhalation of crystalline silica dusts is strictly related to the physicochemical properties of the particles, which, in turn, are mostly determined by the "origin" and the history of the dust. Several physicochemical properties have been reported to modulate silica pathogenicity. None of them simply correlate with the reported toxicity in all the systems used to study silica pathogenicity. This confirms, on the one hand, that several properties are implicated at the same time, and on the other that pathogenicity is the result of a multistage process. There is a general consensus on the key role played by alveolar macrophages in silica-related diseases. For this article the cytotoxicity of a large variety of silicas, including rather unusual forms, with controlled micromorphology and surface properties, has been studied on a mouse monocyte-machrophage tumor cell line successfully employed in previous studies on cristobalite (Fubini et al., 1999). When compared on a per unit surface basis, crystalline silicas were more cytotoxic than amorphous ones, with the notable exception of stishovite, the nonpathogenic crystalline polymorph, with octahedrally coordinated silicon atoms. Among the amorphous ones, a diatomaceous earth and a powdered silica glass exhibited an intermediate toxicity, higher than what was elicited by a pyrogenic silica. In this study a new class of crystalline silicas have been considered, pure-silica zeolites, which constitute a new morphological entity with which cells may be confronted. The cytotoxicity of these samples varies from inert to highly cytotoxic, covering all the range of toxicity covered by the traditional silica dusts. We discuss the influence of morphological properties and surface reactivity on the cytotoxicity of several pure-silica zeolites. The extent of exposed surface and the shape of the particles correlate with cell toxicity. The lower cytotoxicity of one "non pathogenic quartz" and of an aluminum-coated Min-U-Sil quartz, compared with the original pathogenic Min-U-Sil quartz, suggest a depressive effect of the aluminum ions present at the surface of both quartzes. The extreme variability in the biological response to crystalline silicas is confirmed and a new class of materials is brought to the study of the mechanisms of silica pathogenicity. PMID- 26368604 TI - Lung Biopersistence and in Vitro Dissolution Rate Predict the Pathogenic Potential of Synthetic Vitreous Fibers. AB - Here we review the past decade of research on inorganic fiber toxicology, which demonstrates that fiber biopersistence and in vitro dissolution rate correlate well with fiber pathogenicity. Test fibers for these studies included eight synthetic vitreous fibers (SVFs)-refractory ceramic fiber (RCF1), four fiber glasses (FCs), rock wool, slag wool, HT stone wool-and two asbestos types (crocidolite and amosite). Fiber toxicology and biopersistence were investigated using rodents exposed by inhalation. To evaluate chronic inhalation toxicity, rodents were exposed nose-only to ~ 100 fibers >20 um in length (F > 20 um)/cm(3), 6 h/day, 5 days/wk, for 2 yr (rats) or 11/2 yr (hamsters). To evaluate lung biopersistence, rats were exposed nose-only for 5 days to fiber aerosol; lung burdens were then analyzed during 1 yr postexposure. In vitro dissolution rate was evaluated in a flow-through system using physiological solutions that mimic the inorganic components of extra- and intracellular lung fluids. The 10 test fibers encompassed a range of respiratory toxicities, from transient inflammation only to carcinogenesis. Lung clearance weighted half-times (WT1/2) for F > 20 um were 6-15 days for stonewool, building insulation FCs, and slag wool; 50-80 days for rock wool, 2 special-application FCs, and RCFI; and >400 days for asbestos. WT1/2 correlated with pathogenicity: The rapidly clearing fibers were innocuous (insulation FCs, slag wool, and stonewool), but the more biopersistent fibers were fibrogenic (rock wool) or fibrogenic and carcinogenic (special-application FCs, RCFI, amosite and crocidolite asbestos). In vitro dissolution rates (k dis= ng/cm(2)/h) of the 10 fibers at pH 7.4 or 4.5 ranged from < 1 to >600. Fibers that dissolved rapidly in vitro also cleared quickly from the lung and induced only transient inflammation in the chronic studies. In contrast, fibers that dissolved slowly in vitro were biopersistent in the lung and tended to induce permanent pathogenicity. Other in vitro studies of fiber degradation suggest that, in addition to fiber dissolution, fiber leaching and subsequent transverse breakage may also be important mechanisms in lung biopersistence and hence pathogenicity. The validity of using lung biopersistence for predicting the potential pathogenicity of SVFs is confirmed by this research. The research also supports the use of in vitro fiber degradation at pH 7.4 and/or pH 4.5 as an indicator of SVF potential pathogenicity. PMID- 26368605 TI - Particle Contamination in Experimental Fiber Preparations. AB - Two samples of refractory ceramic fibers (RCF1 and RCF1a) were tested in rats exposed by inhalation for 3 wk and followed thereafter for 12 mo. RCF1 and RCFIa have similar fiber chemistry but differ in the fiber size distributions and the contents of nonfibrous particles (2% for RCFIa, 25% for RCFli. For both test samples the target aerosol concentration was 130 fibers/ml > 20 um but the RCF1 aerosol contained more short fibers (less than 20 um long) and more nonfibrous particles. Radioactive tracer measurements carried out during a period of 90 days after exposure demonstrated an almost complete abolition of alveolar clearance in RCFI-exposed animals. With RCFIa the half-time of(46)Sc2O3 particles was 80 days, compared to 60 days for controls (not statistically different). Biochemical and cytological analyses were carried out in bronchoalveolar lavage at days 3, 17, 31, 94, and 365 postexposure. They revealed a more important and more persistent inflammation in RCFI-exposed animals compared to RCFIa. These observations show that the biological activity of synthetic vitreous fibers (SVFs) assessed by inhalation experiments depends not only on the chemical composition of the fiber type but also on the physical characteristics of the test sample. They are in line with results of previous studies and support the hypothesis of a synergistic effect between fibrous and nonfibrous particles. They raise questions about the interpretation of the so called RCC experiments in which the several SVFs samples tested were not prepared using the same method and differed in their physical characteristics. In particular, these differences existed especially between the RCF and MMV F samples. PMID- 26368606 TI - The Occurrence of Quartz in Coal Fly Ash Particles. AB - In spite of the presence of quartz, coal fly ash can be considered as a nuisance or inert dust. Respirable crystalline silica (e.g., quartz) is notorious for the induction of, for example, progressive massive fibrosis (PMF); besides, in 1997 the IARC stated that crystalline silica in the form of quartz or cristobalite from occupational sources is carcinogenic to humans. Quartz is present in both coal and residual ash. Ash originates from combustion of pulverised coal and, once removed from the flue gases by electrostatic precipitators (ESPs), it is called pulverized fuel ash (PFA). Thus, occupational exposure to PFA could also include exposure to silica. However, epidemiological studies did not show evidence of progressive massive fibrosis (PMF). In vitro tests demonstrated that PFA is less toxic than silica, and in vivo data of PFA did not support the importance of silica content for toxicity. Commissioned by the Dutch coal-fired power plants, KEMA has started a research project to determine the quartz content in coal and the corresponding PFA. It appears that on average 50% of the a-quartz in coal is found again in the total fraction of PFA (D50(ae) 31 um, where Dsotae) is the aerodynamically mass median diameter), whereas 16% is found in an even finer fraction (D50(ae) 10 um). The remaining part of the quartz is embedded in a glass phase. Scanning electron microscopy (SEM) with x-ray microanalyses (XMA) of cross-sections of 11,130 ash particles showed that quartz in PFA is present as unmelted sand particles. These quartz particles are angularly shaped. However, two types are to be distinguished: free coarse angular quartz particles (not respirable) and small angular quartz particles within the PFA particles. From the SEM/XMA results, it has to be concluded that the quartz in the respirable fraction is predominantly present within the original molten PFA particle. Since the effects of quartz are surface related, this elucidates the negative results of quartz-related effects of PFA in epidemiological, in vitro and in vivo studies. Besides, the amount of the total alpha-quartz in the respirable fraction of the ashes studied is less than 0.2%, so probably the Dutch occupational quartz standard of 0.075 mg m(-3) will not be exceeded. PMID- 26368607 TI - Effect of Desferrioxamine on Silica-Induced Pulmonary Reaction. AB - Surface iron on a mineral particle may be a major mediator of mineral-dust induced toxicity, because iron on the surface of the particle acts as a Fenton catalyst to produce hydroxyl radical from hydrogen peroxide. Desferrioxamine (DF), an iron chelator, might inhibit the process of silica-induced pulmonary reaction. To test this assumption, we investigated the protective effect of DF on lipid peroxidation of cell membrane, production of inflammatory cytokine, and fibroblast proliferation by crystalline silica for an in vitro model. The Fenton activity of silica was decreased by preincubation with DF. Marked decreases in malondialde-hyde (MDA) levels were seen in the DF-treated silica group compared with the untreated group. DF inhibited not only silica-induced release of tumor necrosis factor-alpha (TNF-alpha) and interleukin-8 (IL-8) from A549, but also fibroblast proliferation. The therapeutic effect of DF on experimental silicosis in rat was also studied using total cell count with differential percentage in bronchoaiveoiar lavage fluid, the amount of hydroxyproline in lung, and examination of a histologic section. DF significantly reduced inflammation and fibrosis compared with the untreated control. From these results, we concluded that DF might play a role in the inhibition of silica-induced pulmonary reaction. PMID- 26368608 TI - Ambient Particulate Matter Induces Oxidative Dna Damage in Lung Epithelial Cells. AB - Although epidemiological studies have established a correlation between PMIO levels and acute cardiovascular and respiratory complications, hardly any data is available on possible chronic effects such as cancer. The purpose of this study was to investigate the production of free radicals by ambient particulate matter (TSP) and to link these data to oxidative DNA damage in lung epithelial cells. In line with previous findings on PMIO, supercoiled plasmid DNA was depleted by JSP as well as JSP supernatant (p < .001), and this effect was reduced in the presence of mannitol (5 mM). Using electron spin resonance (ESR) and the spin trap dimethyl-1-pyrroline N-oxide (DMPO) we were able to show that hydroxy/radicals ('OH) are formed from both JSP and JSP supernatant. The DMPO-OH signal was completely abrogated when TSP was preincubated with deferoxamine (5 mM), showing the importance of iron and other soluble metals in this process. Atomic absorption spectroscopy (AAS) analysis of the TSP supernatant showed the presence of soluble Fe, V, and Ni (respectively 253.0, 14.7, and 76.0 u/g insoluble TSP). To investigate the biological significance of OH formation by TSP, 8-hydroxydeoxyguanosine (8-oxodC) was measured in a rat type II cell line by immunocytochemistry. The formation of this hydroxyl-radical-specific DNA adduct was increased twofold (p < .01) after incubation with TSP supernatants, and this effect was inhibited by deferoxamine (p < .01). In summary, our results provide direct evidence that ambient particulate matter generates hydroxyI radicals in acellular systems. Furthermore, we showed that these particulates induce the hydroxyl-radical-specific DNA lesion 8-oxodC in lung target cells via an iron mediated mechanism. PMID- 26368609 TI - Oncogenes and Tumor Suppressor Genes in the Carcinogenicity of Fibers and Particles. AB - Asbestos fibers and crystalline silica are carcinogenic to humans when inhaled into the lungs. Asbestos fibers and cigarette smoke most likely act as cofactors in the induction of lung cancer. Point mutations in the K-ras oncogene and the p53 tumor-suppressor gene are frequent in lung cancers and are consistent with the known mutagenic spectrum of tobacco-smoke carcinogens. The FHIT tumor suppressor gene is also frequently inactivated in lung cancers of smokers and in workers who were exposed to asbestos. Recent molecular studies of p53 tumor suppressor gene mutations and p53 protein expression in the lungs of patients with lung cancer and occupational exposure to crystalline silica and other dusts have been conducted. Mutations in the p53 gene were detected at a frequency similar to those in smoking-related lung cancers. Expression of p53 protein can be detected by immunohisto-chemistry in preneoplastic epithelial lesions in the lungs of smokers and workers. Human malignant mesotheliomas frequently show overexpression of p53 protein; however, point mutations at the p53 tumor suppressor gene or ras oncogene locus are rare. Most cases of malignant mesotheliomas have codeletions of the p15 and p16 tumor suppressor genes and alterations at the NF2 tumor suppressor gene locus with monosomy of chromosome 22. The molecular alterations characteristic of malignant mesotheliomas may develop during later stages of tumor progression and may not reflect the direct genotoxic effects of fibers on the target cell population. PMID- 26368610 TI - Genotoxicity Versus Carcinogenicity: Implications from Fiber Toxicity Studies. AB - Although the association between exposure to asbestos fibers and the development of lung cancer and mesothelioma has been well established in humans, the carcinogenic potential of other natural and man-made fibers/particles is not clear. Various in vitro genotoxicity studies have been employed to assess their in vivo carcinogenic potential. Studies using mammalian cell models have suggested that fiber dimensions, surface properties, physical durability, and cell and tissue responses are important criteria for the carcinogenicity of the fibers. Studies using oncogenic transformation as an endpoint have shown that asbestos fibers can induce malignantly transformed foci in certain rodent cells and that oxygen radicals are important in the toxic, oncogenic transforming, and mutagenic effects of asbestos fibers. The mutagenicity of asbestos in mammalian cells have been demonstrated using several model systems that can detect large multilocus deletions. These findings provide a direct link between chromosomal abnormalities that have frequently been demonstrated in fiber-exposed human and rodent cell lines and carcinogenicity in vivo. Although asbestos has not been shown to malignantly transform primary human epithelial cells, it can induce neoplastic conversion of immortalized human bronchial epithelial cells in a stepwise fashion and provides a unique opportunity to assess the molecular alterations associated with each stage of the neoplastic process. PMID- 26368611 TI - Effects of Crocidolite Fibers on the Peritoneal Mesothelium of Rats. AB - The assay of intraperitoneal (ip) injection to rats was used as experimental system to study the mechanisms of carcinogenic effects of fibrous dusts. With this test system, fibers were shown to induce mesothelioma in the peritoneal cavity. Although the data of the ip assay are discussed controversially in terms of risk assessment, it is a valuable tool to investigate the molecular mechanisms of mesothelioma carcinogenesis in vivo. This test system allows one to investigate both the effects of fibers on signal transduction and the genotoxic potential of fibers. On the level of mRNA expression, different stages of fiber induced tumor development in the peritoneal space were examined using differential display techniques. Genes of signal transduction pathways are mainly affected by the fiber treatment; for example, the activation of genes for the AP 1 transcription factor could be observed in the tissues of the peritoneal cavity. Thus, our in vivo data confirm the findings reported from cell culture systems. Moreover, our results from the differential display assays reveal that genes involved in the integrin-linked signal transduction are upregulated. In addition, the ip assay can be applied to transgenic animals to perform mutagenicity testing. Using the Big Blue transgenic animal system, we provide data of a significant increase in mutation frequency after treatment with crocidolite asbestos. PMID- 26368612 TI - Occupational and Environmental Factors Enhancing the Genotoxicity of Asbestos. AB - Epidemiological and experimental studies have suggested the enhancement of asbestos-induced disease processes by simultaneous exposure to kerosene, its soot, and cigarette smoke in asbestos-exposed animals as well as in humans. To determine the influence of these factors on the genotoxic potential of asbestos, a micronucleus test was performed in Syrian hamster embryo fibroblasts (SHE) and human lymphocytes. To observe the specific chromosomal damages, multicolor fluorescence in situ hybridization (FISH) was done in the lymphocytes from smokers and nonsmokers exposed in vitro to asbestos. Significantly higher numbers of micronuclei were observed in SHE cells after combined treatment with chrysotile and kerosene soot (111 micronuclei/1000 cells) in comparison to chrysotile and kerosene soot separately. Kinetochore staining revealed mainly clastogenic effects in all the cases. In human lymphocytes exposed in cultures to chrysotile and crocidolite the numbers of micronuclei were found higher in smokers than nonsmokers. Multicolor FISH assay suggested that asbestos fibers inflict high damage within 1q12 and in the region between 1cen and 1q12 of chromosome 1. In the exposed population of an asbestos cement factory, the highest genetic damage was found in the blood lymphocytes of exposed smokers. The study suggests that smokers occupationally exposed to asbestos and domestically to kerosene soot are at higher risk for the early development of asbestos-induced diseases. PMID- 26368613 TI - Hyperplastic and Neoplastic Changes in the Lungs of Rats Treated Concurrently with Chrysotile Asbestos and N-Nitrosoheptamethyleneimine. AB - This study investigated the combined effect in rat lungs of simultaneous exposure to chrysotile asbestos and N-nitrosoheptamethyleneimine (NHMI), with the objective of determining the potential for chrysotile to promote or otherwise enhance the pathological responses to this potent rodent lung carcinogen. Groups of 15 or 20 male and female animals were treated with 0, 3, or 10 mg kg(-1) NHMI subcutaneously, once a week for 10 wk, plus either clean air (control) or 50 mg m(-3) chrysotile by nose-only inhalation for 4 wk. A broad range of pulmonary metaplastic, hyperplastic, and neoplastic lesions was observed. Effects were more marked in male than in female animals. NHMI treatment increased the incidence of hyperplastic lesions, with apparent augmentation by chrysotile exposure (not statistically significant). Similarly, a "promoting" effect of chrysotile in the induction of lung tumors was observed, with all but 2 of the 11 primary tumors detected being in animals treated with both NHMI and asbestos. However, this apparent interaction was again not confirmable statistically, probably because of the low number of observed tumors (stemming from premature termination of the experiment). The study results are in line with those of similar previous studies, which found a higher incidence of hyperplastic and neoplastic changes in animals treated with both nitrosamine and asbestos than in those given nitrosamine alone. It is proposed that the method described (with minor modification) could be used to investigate either (1) the ability of other inhaled particles to augment NHMI carcinogenicity, or (2) the propensity of other chemical carcinogens to interact with asbestos in the production of pulmonary neoplasms. PMID- 26368614 TI - A Comparison of Pleural Mesotheliomas Induced by Asbestos or SV40 Virus in Syrian Golden Hamsters. AB - Pleural mesotheliomas are a well-known consequence of exposure to asbestos in both humans and animals. However, there are cases of mesothelioma in humans for which there is little or no known exposure to asbestos. Mesotheliomas have also been produced in hamsters infected with simian virus 40 (SV40), a contaminant of early polio vaccines, which was shown to replicate in individuals inoculated with the vaccine. Recently, wild-type SV40 has been detected in human mesotheliomas as well as other types of neoplasms. Because the tumors were induced with such dissimilar agents, we evaluated mesotheliomas produced in hamsters after intrapleural injection of SV40 compared to those produced after inhalation exposure to amosite asbestos to see if there were differences in the development and morphology of the tumors. Although the mesotheliomas produced by both agents were clearly of mesothelial origin based on standard morphological criteria, there were clear differences. The SV40-induced tumors occurred with a short latency period, were large multicentric lesions with pleural effusion that always caused death within 3 to 6 mo, and were largely composed of small round cells growing in a uniformly tubulopapillary pattern with many areas of sarcomatous change. They had a minimal amount of stroma and tended to invade the adjacent tissues. The unaffected pleura showed no evidence of fibrosis. In contrast, the mesotheliomas induced by asbestos occurred much later (most after 18 mo), were rarely (<10%) the cause of death, and were typically very small with little evidence of pleural effusion. While they also had a tubulopapillary pattern, they were composed of larger cells with more abundant cytoplasm and sarcomatous change was rare. The adjacent pleura typically showed marked evidence of fibrosis and local invasion was rarely encountered. Whether these striking morphological differences between SV40- and asbestos-induced mesotheliomas in hamsters have a correlate in humans is not known. It would be useful to conduct a similar comparison of mesotheliomas from humans known to have been exposed to high levels of asbestos to those with no known exposure to see if similar morphological differences exist. PMID- 26368615 TI - Investigations of DNA Damage Produced by Asbestos Fibers in Rat Pleural Mesothelial Cells. AB - Asbestos fibers have long been considered nongenotoxic because of the absence of point asbestos-treated cells mutations in several assays. More recently, some studies have demonstrated that various kinds of DNA damage were observed in asbestos-treated cells, namely, base hydroxylation, DNA adducts, and DNA breaks. The occurrence of DNA breakage has been mostly suggested by indirect methods. We investigated DNA damage produced by Rhodesian chrysotile fibers in a model of normal rat pleural mesothelial cells (RPMC) developed in our laboratory, by different approaches. DNA breakage and repair of DNA damage were evidenced by the enhancement of the activity of poly(ADP)ribose polymerase (PARP) and of unscheduled DNA synthesis, and were suggested by cell cycle arrest in asbestos exposed RPMC. In growing cells, a cell cycle arrest was observed at the G1-S transition. DNA breakage was also demonstrated by the formation of comets in single-cell gel electrophoresis (SCGE) assay. The results showed that comets were generated by asbestos, as assessed by the significant increase in mean tail length and mean tail moment after exposure to asbestos. In RPMC-TSV40 (i.e., RPMC in which the protein was p53 inactivated by infection with a retroviral recombinant encoding the large T antigen of the SV40 virus), the comet parameters were moderately enhanced. Regarding previous results of an impairment of DNA repair in RPMC-TSV40, the SCGE results suggest that chrysotile caused DNA breakage in both RPMC and RPMC-TSV40. Moreover, these findings lead to the hypothesis that DNA repair was impaired in RPMC-TSV40. PMID- 26368616 TI - Study of Cell Division Aberrations Induced by Some Silica Dusts in Mammalian Cells in Vitro. AB - Previously we observed that some crystalline and amorphous (diatomaceous earths) silicas (but not pyrogenic amorphous silica) induced morphological transformation of Syrian hamster embryo (SHE) cells. In order to explore the mechanisms of the silica-induced cell transformation, in this study we have examined the possibility that silica may cause genomic changes by interfering with the normal events of mitotic division. The SHE cells were exposed to transforming samples of Min-U-Sil 5 quartz and amorphous diatomite earth (DE) as well as to inactive amorphous synthetic Aerosil 0X50 at concentrations between 9 and 36 MUg/cm(2) of culture slide. Effects on the mitotic spindle and on chromosome congression and segregation through the mitotic stages were concurrently examined by differential and indirect immunofluorescence stainings using anti-beta-tubulin antibody. Min-U Sil 5 and DE dusts induced a significant increase in the number of aberrant mitotic cells detected by differential staining. Increased frequencies of monopolar mitoses and scattered chromosomes as well as a small incidence of lagging chromosomes in DE-treated cells were observed. The immunostaining was more efficient in the detection of spindle disturbances. Min-U-Sil induced a significantly concentration-dependent increase of monopolar spindles. At the highest concentration, highly disorganized prophase spindles and prometaphase multipolars were observed. These damages caused a concentration-dependent decrease in metaphase to anaphase transition. DE-induced spindle aberrations did not reach significant levels over control, although increase in monopolar and multipolar spindles were recorded. Exposure to OX50 particles did not disrupt spindle integrity. To determine whether micronuclei (MN) arise from divisional abnormalities induced by the active samples, we performed in SHE and human bronchial epithelial cells kinetochore (K)-specific and centromere (C)-specific staining, respectively. A concentration-dependent increase in K(+) and C(+) MN with increase of K(+)/K(-) and C(+)/C(-) MN ratio were induced by Min-U-Sil in both cells systems. The DE sample was positive only in SHE cells. The results suggest that some silicas are potential aneugens by disturbance of cell division, leading to genomic imbalance that can be one of the mechanisms of silica-induced cell transformation. PMID- 26368617 TI - In Vivo Genotoxicity of Crystalline Silica as Evidenced by Micronuclei in Pulmonary Alveolar Macrophages: Low-Dose Study. AB - We have previously published results showing time-course data (Leigh et at., 1998) and a dose-response relationship between macrophage micronucleus formation and crystalline silica dose in intratracheally instilled rats at 2.5, 7.5, and 22.5 mg dosage, without an inert dust control (Wang et al., 1997). We here extend this study to low dose (0.025, 0.25, and 2.5 mg crystalline silica) with 2.5 mg TiO2 control. Specific-pathogen-free male Wistar rats were intratracheally instilled with 0.5 ml saline, and 0.025 mg, 0.25 mg, or 2.5 mg crystalline silica (Min-U-Sil 5) and 2.5 mg TiO2 suspended in 0.5 ml saline (5 rats in each group). Five days after instillation, rats were sacrificed and 10 ml of bronchial alveolar lavage fluid was obtained. A 100-MU1 volume was placed on slides by Cytospin centrifugation, stained with Diff-Quik, and 1000 macrophages were scored for micronuclei (defined by diameter < half main nucleus; same staining; round shape and complete separation). Micronucleus incidence was significantly elevated (p < .01) at the lowest crystalline silica dose compared with saline control. There was a dose-response relationship with crystalline silica exposure. Numbers (mean +/- SEM) of micronucleated macrophages per 1000 macrophages scored were 1.5 +/- 0.5 (saline), 3.3 +/- 0.3 (0.025 mg crystalline silica), 7.1 +/- 0.4 (0.25 mg crystalline silica), 10.1 +/- 0.3 (2.5 mg crystalline silica), and 0.9 +/- 0.3 (2.5 mg TiO2). We conclude that intratracheal instillation of low doses of crystalline silica can induce micronucleus formation in alveolar macrophages in a dose-related manner. We further believe that this is not a nonspecific effect, consistent with crystalline silica being a genotoxic carcinogen. PMID- 26368618 TI - DNA Damage and Inflammation in the Rat Quartz Model: Differences in Inflammatory Response and Formation of Oxidative DNA Adducts to High and Low Dose of DQ12 Quartz. AB - Chronic exposure to poorly soluble particles such as quartz and diesel soot produces dose-dependent inflammatory responses in the rat lung. It has been shown that the inflammation in the rat lung causes persistent oxidative DNA damage and mutations in proliferation-competent cells, which are thought to be critical for tumorigenesis. In measuring various inflammatory parameters to a multidose quartz exposure in parallel with the amount of 8-oxoguanine (8-oxoGua) on the cellular level in rat lung, mechanistic data for understanding the underlying processes could be gained. Rat lungs (female Wistar, 180-220 g/bodyweight) were instilled with quartz DQ12 (doses 0.3, 1.5, and 7.5 mg/animal; controls: corundum at the same doses and physiological NaCl) and analyzed 90 days after intratracheal instillation. The bronchoalveolar lavage (BAL) fluid was determined for inflammation markers (differential cell count, protein, lung surfactant lipids, and tumor necrosis factor alpha); tissue sections of lungs were investigated for the amount of 8-oxoGua on the cellular level using an antibody against 8-oxoGua. The results reflect different responses for quartz versus all controls and show a clear dose-response relationship. Quartz elicited inflammatory reponses determined in the BAL fluid even at the low dose (0.3 mg/animal). In contrast, the level of 8-oxoGua in the lung of animals exposed to 0.3 mg quartz was not statistically increased above controls, whereas doses of 1.5 mg and 7.5 mg caused significant elevations. The data obtained indicate a no-effect level for the persistence of the mutagenic DNA adduct 8-oxoguanine in the epithelial lung cells at a low-dose quartz exposure that is still inflammatoric and fibrogenic. PMID- 26368619 TI - Lung Carcinogenesis by Diesel Exhaust Particles and the Carcinogenic Mechanism Via Active Oxygens. AB - In an experiment to clarify the involvement of oxygen radicals in lung carcinogenesis induced by diesel exhaust particles (DEP), we found that there is a strong relation between lung tumor response and formation of 8 hydroxydeoxyguanosine (8-OHdG) in lung DNA of mice administered DEP by repeated intratracheal instillation. Repeated intratracheal instillation of DEP also induced the activity of cytochrome P-450 reductase in the lungs as a representative enzyme of superoxide generation, and two types of nitric oxide (NO) synthase, cNOS and iNOS, in the lungs. On the other hand, activities of CuZn superoxide dismutase (SOD) and Mn-SOD antioxidant enzymes were depressed by the instillation of DEP. These results suggest that generation of superoxide, hydroxyI radical, and nitric oxide are increased in epithelial cells in airways, and that the increased superoxide and nitric oxide react very easily to produce peroxynitrite (ONOO(-)). The peroxynitrite also produce hydroxyI radical. The hydroxyl radical may play an important role in carcinogenesis by DEP. PMID- 26368620 TI - Chronic Inflammation and Tumor Formation in Rats After Intratracheal Instillation of High Doses of Coal Dusts, Titanium Dioxides, and Quartz. AB - Coal mine dust's possible carcinogenicity has recently drawn attention because of the IARC review of quartz, some new epidemiological data in German coal miners, and findings on other poorly soluble, nontoxic dusts in the rat. The aim of this study was to investigate persistent inflammation and tumor response in the rat after intratracheal instillation of two coal dust samples and other dust preparations. Female Wistar rats (190 g) were instilled with ground lean coal (60 mg) coal mine dust (60 mg), DQI2 quartz (5 mg), and fine (60 mg) and ultrafine (30 mg) TiO2. After 129 wk rats were killed, tumors detected by microscopy, and inflammation by light microscopy after specific antibody staining for macrophages and granulocytes. Increased alveolar macrophages (AM) and interstitial granulocytes were still present in dust-treated animals. Both AM and granulocytes per surface area were related to tumor incidence when all materials were plotted in one graph, and can be interpreted as effects of overload. Differences in tumor formation between fine and ultrafine TiO2, despite similar inflammatory response, are probably caused by a direct effect of ultrafine TiO2 after interstitialization. It is concluded that coal dust is another poorly soluble, nontoxic dust, which at high enough dose rate causes overload, inflammation, and tumor response in the rat. PMID- 26368621 TI - Systemic Effect of Particulate Air Pollution. AB - The association in epidemiological studies between particulate air pollution (PM10) and increased mortality and morbidity from cardiovascular disease is well established. However, the mechanism(s) by which PM10 produces these effects is unknown. We have developed a hypothesis that ultrafine components of PM10 cause lung inflammation by creating local lung oxidative stress, which activates transcription factors such as NF-kB and hence the transcription of genes for inflammatory mediators. In a series of studies in vivo in the rat and using cultured airspace epithelial cells in vitro, we have tested this hypothesis using environmental PM10 and fine (CB 260 nm in diameter) and ultrafine (UfCB, 14 nm in diameter) carbon particles, since carbon is a major component of PM10 We have shown that compared with CB, which produces trivial effects, UFCB and PM10 produce local lung inflammation, increased epithelial permeability, and evidence of oxidative stress. We have also shown that PM10 also activates NF-kB in airspace epithelial cells. We also hypothesized that the local lung inflammation produced by PM10, may result in systemic effects, in particular systemic oxidative stress and enhanced blood coagulation, which may have a role in the adverse cardiovascular effects induced by PM10. To test this hypothesis we measured oxidative stress and changes in coagulation factors in plasma following the inhalation of UFCB, CB, or instillation ofPM,10 in the rat. Immediately after 7 h inhalation of UFCB (1000 (g/m(3)) there was a significant decrease in the antioxidant capacity in rat plasma, which fell further 16 and 48 h after cessation of the inhalation. A similar fall in plasma antioxidant capacity was shown 6 h after instillation of PM10 (125 tig). In contrast, there were no significant changes in antioxidant capacity in rats after 7 h of inhalation of CB at similar concentrations. The levels of factor VII in plasma, which is a key factor in the intrinsic pathway of coagulation cascade, increased at time points from 6 h to 7 days after inhalation of UFCB, but did not change after CB exposure. There were no changes in plasma fibrinogen or other coagulation factors after inhalation of particles. Thus, inhalation of ultrafine carbon black particles and instillation of PMio in rats decreases plasma antioxidant capacity as an indication of systemic oxidative stress. Ultrafine carbon black particles also cause increased factor VII levels in the plasma, a known risk factor for adverse cardiovascular events. These studies help to explain the relationship between the levels of particulate air pollutants and cardiovascular morbidity/mortality. PMID- 26368622 TI - Inhalation of Asbestos Fibers and Consequent Expression of Peptide Growth Factors. AB - It would be impossible to completely review this broad topic in the space and time allowed, lust as we must make choices when focusing on a research topic, this brief overview of particles and fibrosis deals with a small corner of our current thinking on the molecular mechanisms through which inhaled particles mediate fibroproliferative lung disease. At some point, there must be a common pathway of action because the fundamental process after any exposure involves fibroblast proliferation and production of extracellular matrix, that is, scar tissue. Thus, if we can understand how to control the fibroblast cell cycle and those genes that code for matrix components, it may be possible to develop effective therapeutic modalities for pulmonary fibrosis where none now exist. To control cell cycle and matrix genes that are expressed due to particle exposure, investigators have focused on certain peptide growth factors. The genes that code for these factors as well as the genes and oncogenes that are expressed when the peptides bind to their cognate receptors offer the best opportunities for understanding the molecular mechanisms of particle-induced lung fibrosis. As an example, mice with the genes knocked out for both the 55- and 75-kD receptors for tumor necrosis factor-alpha (TNF-alpha) are protected from the fibrogenic effects of inhaled asbestos and silica. Expression of other peptide growth factors in these animals is reduced, leading to a central working hypothesis, that TNF-alpha is a "master switch" that controls the expression of other more downstream factors that mediate components of the fibrogenic process. There is ample evidence of TNF-alpha expression in animal models and in populations of dust exposed workers to support this postulate. In addition, it appears that transforming growth factor beta (TGF-beta) is the primary peptide that controls production of extracellular matrix. Blocking of TGF-beta expression in animal models prevents fibrosis, and the use of specific antisense RNA blocks both TGF beta and collagen gene expression in primary lung fibroblasts. Conversely, an adenovirus vector that transduces expression of TGF-beta to the bronchiolar alveolar epithelium induces diffuse fibrogenesis in rats and mice. Thus, particle induced pulmonary fibrosis is a complex process that will be understood only after we dissect and elucidate the signal transduction pathways that control growth factor and matrix gene expression. The emerging technologies for developing transgenic and knockout mice, viral vectors for gene transduction, antisense approaches, and microarray gene analysis will finally allow us to accomplish these goals. PMID- 26368623 TI - Asbestos-Related Pleural Thickening is Independently Associated With Lower Levels of Lung Function and with Shortness of Breath. AB - This study investigated the relative contribution of asbestos-related pleural thickening (PT) to lung function indices and to respiratory symptoms. A group of 828 former asbestos cement workers enrolled in a cross-sectional and cohort study of respiratory morbidity and submitted to a detailed occupational history, respiratory symptoms questionnaire, spirometry, postero-anterior chest x-ray, and high-resolution computed chest tomography (HRCT). Asbestos exposure was assessed by years of exposure (a semi-quantitative method), cumulative exposure, and latency time from first exposure. Smoking was assessed in pack-years. PT and asbestosis were assessed according to HRCT criteria. Statistical analysis included descriptive analysis, univariate and multivariate analysis of variance for comparisons of factors related to PT, stepwise multiple regression analysis for continuous dependent variables, and logistic regression analysis for dichotomous dependent variables. Mean age was 51.4 (SD 10.5) years, mean years of exposure 12.4 (SD 8.8), mean cumulative exposure 79.9 (SD 68.5), and mean latency time 25.2 yr (SD 10.4). Of the 828, 238 (28.7%) were smokers, 288 (34.8%) former smokers, and 302 (36.2%) nonsmokers. PT was present in 246 (29.7%) and asbestosis in 74 (8.9%); 97 (11.9%) had shortness of breath of Grade III or more. PT subjects had lower height-adjusted forced vital capacity (FVC) and forced expiratory volume in I s (FEV1) and lower FEV1/FVC% (p < .00001 for all). Variables significantly related to PT were age (p < .000 1), years of exposure (p < .0000 1), cumulative exposure (p < .00001), latency time (p < .00001), pack years (p < .0000 1), and asbestosis (p < .00 1). In a multiple stepwise regression model, after controlling for confounders, height adjusted FEV1 and FVC were in versely and significantly associated with PT, mainly when associated with asbestosis. A logistic regression model with shortness of brea th as the dependent va riable, con trolled for confounders, showed that PT was significa ntly associated with the symptom, even without asbestosis. In conclusion, PT is independently associated with lower va lues of FEV1 and FVC. PT is also independently associated with an increased risk of shortn ess of breath report. PT should be considered as a disease for clinical follow up and for compensa tion claims. PMID- 26368624 TI - Short-Term Inhalation Exposure of Healthy and Compromised Rats and Mice to Fine and Ultrafine Carbon Particles. AB - Epidemiological studies have consistently shown associations between acute pulmonary effects and relatively low levels of ambient particulate matter (PM). The present study was carried out to examine the pulmonary toxicity of inhaled fine (FCB) and ultrafine carbon (UFC) particles as model compounds for carbonaceous (primary) PM, and to identify whether particle size, particle number, and/or mass could be critical in inducing the deleterious effects. Healthy and compromised rats and mice were exposed for 4 h/day during 3 consecutive days to 10(4) or 10(5) fine carbon black (~300-500 nm), or 10(5) or 10(6) ultrafine carbon (~30-60 nm) particles/cm(3), covering a mass range of about 10 to 10,000 u/m(3). Separate groups of rats were also exposed to a combination of FCB and fine ammonium nitrate at similar number and mass concentrations. Animals were sacrificed the day after the last exposure to determine their pulmonary responses using bronchoalveolar lavage fluid (BALF) analysis and lung histopathology. Exposure to FCB resulted in early signs of lung injury. Effects were not enhanced in compromised animals when compared to healthy animals. Exposure to UFC particles at similar and higher number concentrations did not induce any biologically relevant changes. These data may indicate that at number concentrations occurring in ambient air, the size of the particles (in air) is more important than their number. PMID- 26368625 TI - Comparative Injurious and Proinflammatory Effects of Three Ultrafine Metals in Macrophages from Young and Old Rats. AB - The aim of this study was to compare the ability of ultrafine titanium dioxide (Uf-TiO2), ultra-fine nickel (Uf-Ni), and ultrafine cobalt (Uf-Co) to cause damage and stimulation to alveolar macrophages from rats of different ages. Wistar male rats (SPF), aged 2 mo (young) or 20 mo (old), were sacrificed prior to bronchoalveolar lavage (BAL). Alveolar macrophages (AM) from either young or old rats were incubated with Uf-Co or Uf-Ni at a final Concentration of 2.5, 5, 10, 20, and 40 ug/ml, respectively. Macrophages were also incubated with 40 ug/ml ultrafine metals for 12, 24, or 48 h before biochemical indices were evaluated in the supernatant. There were dose-related increases in lactate dehydrogenase (LDH) activity and tumor necrosis factor-alpha (TNF-alpha) in the supernatant of young and old macrophages after treatment with various doses of Uf-Co or Uf-Ni. Both Uf Co and Uf-Ni caused severe macrophage damage, which was reflected in an increase in the relative LDH activity in supernatant. Furthermore, macrophages from old rats released significantly more TNF-alpha than macrophages from young rats, especially after 12-h treatment with Uf-Co. The study has confirmed that three ultrafine metals differ in their toxicity and stimulatory effects on rat alveolar macrophages. Uf-TiO2 was relatively inactive in these assays of toxicity. There were clear differences in susceptibility to these effects in macrophages from young or old rats, with old rats showing a substantially greater TNF-alpha response. The mechanism still remains to be elucidated, but our earlier studies implicated oxidative stress in the proinflammatory effects of these ultrafine metals. In addition, oxidative stress has been implicated in aging. Therefore our data are consistent with the concept that aging is accompanied by oxidative stress that renders the aged lung susceptible to the proinflammatory effects of ultrafines. PMID- 26368626 TI - Comparison of Selected Pulmonary Responses of Rats, Mice, and Syrian Golden Hamsters to Inhaled Pigmentary Titanium Dioxide. AB - We present a preliminary report of a bioassay designed to compare and contrast selected pulmonary responses of female B6C3F1 mice, Fischer 344 rats, and Syrian golden hamsters to inhaled pigmentary titanium dioxide (TiO2). Animals were administered 10, 50, or 250 mg/m(3) TiO2 for 6 h/day and 5 days/wk, for 13 wk. Recovery groups were held for an additional 4-, 13-, or 26-wk period. Following exposure and at each recovery time, TiO2 burdens in the lung and lung-associated lymph nodes were determined. A separate group of animals was used at each time point to assess the inflammatory response of the lung by assaying total protein in bronchoalveolar lavage fluid (BALF) and cytologic examination of cells recovered in BALF. Burdens (mg/mg dry weight) of TiO2 in the lung following exposure to 10, 50, or 250 mg/m(3) TiO2 were 5.2, 53.5, and 170.2 for the mouse; 7.1, 45.1, and 120.4 for the rat; and 2.6, 14.9, and 120.3 for the hamster. With time after exposure, lung burdens of TiO2 particles were decreased and lymph-node burdens increased. Changes in the hamsters' burdens were more rapid than those in mice and rats. Increases in BALF cell numbers (macrophages and neutrophils) and in total protein were observed in all 3 species following exposure to 50 and 250 mg/m(3) TiO2, with the magnitude of response being the grea test in the rat. These responses remained elevated relative to control levels at 26 wk postexposure. Histopathologic examination of lungs showed a concentration dependent retention pattern of particles that varied by species. Hypertrophy and hyperplasia of alveolar epithelium along with alveolar metaplastic and fibrotic changes were observed in rats exposed to 250 mg/m(3) TiO2. Alveolar epithelial proliferative changes were associated with inflammation in mice and hamsters, but the metaplastic and fibrotic changes noted in rats were not present in similarly exposed mice or hamsters. These data suggest that rats exposed subchronically to extremely high concentrations of pigmentary TiO2 differ from mice and hamsters in their cellular responses in the lung as well as in the way they clear and sequester particles. These differences may partly explain the differential outcome of pulmonary responses in various rodent species following chronic inhalation exposure to poorly soluble particles. PMID- 26368627 TI - Protein Carbonyls in Bronchoalveolar Lavage Fluid in Mice, Rats and Hamsters Following Inhalation of Pigmentary Titanium Dioxide Particles. AB - Elevation of protein carbonyls has been implicated in the clinical setting as a result of oxidant damage associated with a number of disease states in both humans and laboratory animals. Protein carbonyls, the product of oxidative modification of amino acid residues, may result from macrophage and neutrophil inflammatory responses to inhaled particles. We hypothesized that increased levels of protein carbonyl groups in the bronchoalveolar lavage fluid (BALF) may serve as a biomarker of oxidative stress in rodents exposed to extremely high airborne concentrations of poorly soluble particles (PSP) of low toxicity. The objective of the present study was to compare the BALF protein carbonyl levels in three rodent species following a subchronic PSP exposure known to result in pulmonary pathology in chronically exposed rats under similar conditions. Female Fischer 344 rats, B6C3F1 mice, and Syrian golden hamsters were identically exposed by whole-body inhalation to concentrations of aerosolized pigmentary titanium dioxide (TiO2)(MMAD and GSD, 1.42 and 1.3 MUm, respectively) for 6 h/day and 5 days/wk for 13 wk. Groups of animals were exposed to 0, 10, 50, or 250 mg/m(3) of pigmentary TiO2. Levels of protein carbonyl groups in BALF were measured at the termination of the 13-wk exposure with an ELISA assay utilizing a 2,4-dinitrophenylhydrazine fluorescent probe. Protein carbonyl levels were elevated in rats at both the mid and high dose (50 and 250 mg/m(3)), while in mice and hamster the levels were elevated only at the high dose (250 mg/m(3)). The elevations in protein carbonyl levels paralleled changes in BALF-associated cytologic and biochemical inflammatory indices, including total protein levels and neutrophil counts. Inflammatory changes in all three species were limited to animals exposed to the highest concentrations of particles. Rats were the only species tested that had coincidental elevation of both protein carbonyls and a high inflammatory response measured in BALF following the 50-mg/m(3) exposure. These results suggest that the measurement of protein carbonyl groups in BALF may be a useful biomarker of particle-induced oxidant change, although this endpoint should be used in conjunction with other oxidative endpoints as a total assessment of oxidant stress. PMID- 26368628 TI - A Morphologic Study on the Fate of Ultrafine Silver Particles: Distribution Pattern of Phagocytized Metallic Silver in Vitro and in Vivo. AB - The distribution pattern of inhaled particles is an important factor for the evaluation of health effects. In this study, we morphologically investigated the fate of agglomerated ultrafine particles in macrophages in vitro and in vivo. Metallic silver (Ag) was chosen as a test particle, since it can be easily produced and detected by elemental and morphologic analyses. Ultrafine Ag particles generated by an electric spark generator in an argon atmosphere were collected on PTFE filters. The particles were suspended in distilled water and adjusted to different concentrations (10 MUg/ml to 1 mg/ml) with phosphate buffered saline (PBS). For the in vitro study, 1774 macrophage cell suspensions (200,000 cells in 400 MUl medium) were plated in small chambers. Six hours later, 100 MUl of the silver-PBS suspension was added to each chamber. For the next 9 days, the chamber slides were examined daily with an inverted microscope in order to detect agglomerated particles in the cell. The medium was changed every day, and Ag in the medium was checked by inductively coupled plasma mass spectrometry (ICP-MS). On days 1, 3, 5, 7, and 9, cells in the chambers were fixed with 2.5% buffered glutaraldehyde and examined ultrastructurally. For the in vivo study using F344 rats, 50 MUg Ag particles were instilled intratracheally. On days 1, 4, and 7 following instillation, rats were sacrificed and the lungs were examined morphologically. The Ag content in the lung, liver, and lung-associated lymph nodes was analysed by ICP-MS. In the in vitro study, the dose-dependent presence of agglomerated particles was observed in 1774 cells. The size and form of particles remained unchanged throughout the observation period. Electron microscopy with x-ray microanalysis showed that both single and agglomerated Ag particles were observed in the dilated phagolysosome of 1774 cells. In the in vivo study, focal accumulation of Ag-particle-laden alveolar macrophages was found. Ag particles were also observed in the alveolar wall. Ag content in the lung was constant between day 1 and day 7, indicating that no rapid particle translocation from the lung to other organs had taken place in this time period. In vitro and in vivo studies suggested that agglomerated Ag particles remained in targets for a given period of time-at least up to 7 days. PMID- 26368629 TI - Gene Expression of Matrix Metalloproteinases in Clara-Cell Secretory Protein Deficient Mice Exposed to Cigarette Smoke. AB - Clara-cell secretory protein (CCSP) is thought to play a role as a regulator of inflammatory response. To investigate how CCSP plays a role in lung remodeling induced by exposure to cigarette smoke, we examined gene expression of matrix metalloproteinases (MMPs) and chemokine mRNA in lungs of mice exposed to cigarette smoke. CCSP-deficient (CCSP-/-) strain 129 and wild-type (WT) strain 129 mice were exposed to sidestream cigarette smoke for 4 h/day, for 4 wk. Expression of MMP-2, MMP-9, interleukin-10 (IL-10), and macrophage inflammatory protein-2 (MIP-2) mRNA in lungs was measured by reverse-transcription polymerase chain reaction (RT-PCR) using p-actin as an internal standard to quantify PCR amplification of mRNA. No significant differences were observed in gene expression of MMP-2, MMP-9, IL-10, and MIP-2 mRNA between CCSP-/- and wild-type mice exposed to cigarette smoke. This suggests that CCSP is not correlated with cigarette smoke-induced pulmonary response through MMPs and chemokines. PMID- 26368630 TI - Role of Mitogen-Activated Protein Kinases, Early Response Protooncogenes, and Activator Protein-1 in Cell Signaling by Asbestos. AB - Cell signaling by pathogenic minerals may initiate the transactivation of genes that are critical to carcinogenesis and fibroproliferative diseases of the lung and pleura. We have shown previously that stimulation of the mitogen-activated protein kinase (MAPK) cascade by asbestos fibers leads to phosphorylation events involved in transactivation of lun and Fos proteins that comprise the activator protein-1 (AP-1) transcription factor. Recently, we have also used AP-1 luciferase reporter transgenic mice and immunocytochemistry to show that transactivation of AP-1 occurs in bronchiolar and alveolar epithelial cells after inhalation of asbestos fibers. After inhalation of asbestos, epithelial cells of the lung also show increased immunoreactivity of pliosphorylated extracellular signal regulated kinases (ERKs 1/2) at sites of fibrogenesis. The availability of lung epithelial cell-specific promoters has allowed the creation of transgenic mice with mutations in the transactivation domains of key receptors and protein intermediates that comprise the MAPK signaling cascade. These rodent models may reveal whether cell signaling events initiated by mineral dusts in epithelial cells are critical to the development of cell proliferation, apoptosis, and lung disease. PMID- 26368631 TI - Nuclear Factor Kappa-B Activation by Particles and Fibers. AB - In recent years, particle research has focused on activation pathways of transcription factors that are known to regulate genes whose abnormal expression is associated with the pathogenesis of particle-associated lung disorders such as fibrosis, cancer, COPD, and asthma. This article reviews the effects of different particles and fibers on the transcriptional activation of nuclear factor kappa-B (NF-kB), which is involved in the activation of a variety of proinflammatory genes. Particulates that have been found to activate NF-kappaB, include asbestos, man-made fibers, quartz, and ambient particulates, such as residual oil fly ashes (ROFA) and diesel exhaust particles (DEP). In line with this, a number of NF kappaB-regulated genes have been found to be upregulated, such as tumour necrosis factor-alpha (TNFalpha), macrophage inflammatory protein-2 (MIP-2), the interleukins IL-6 and IL-8, cyclooxygenase- II (COX-II), and inducible nitric oxide synthase (iNOS). Important mechanisms involved in the activation of NF-kB by particles or fibers include a role for reactive oxygen species, arachidonic acid metabolism, and particle- or fiber-specific physiochemical properties (e.g., transition metals, fiber dimensions) in processes such as lipid peroxidation and (frustrated) phagocytosis. Intracellularly, NF-kappaB may be activated via several pathways, for example, involving protein kinase C, tyrosine kinase, or calpain. Future research on NF-kappaB activation by particles or fibers should aim to further identify these and other pathways and to determine the in vivo significance of this activation in the pathogenesis of lung disease. PMID- 26368632 TI - Cell Signaling in Mesothelial Cells by Asbestos: Evidence for the Involvement of Oxidative Stress in the Regulation of the Epidermal Growth Factor Receptor. AB - Asbestos has been shown to stimulate the mitogen-activated protein kinase signaling cascade after autophosphoryiation of the epidermal growth factor recptor (EGF-R), an event important in regulating the response of cells to extracellular signals. In studies reported here, we have examined whether mineral fibers with known carcinogenicity can be discriminated from nonpathogenic fibers by their ability to upregulate expression of EGF-R protein in mesothelial cells. Crocidolite and erionite, two fibrous preparations known to induce mesothelioma, increased expression of EGF-R protein in a time- and dose-dependent manner, whereas milled (nonfibrous) crocidolite and chrysotile asbestos, two preparations with much less or no ability to induce mesothelioma, did not. Intense patterns of EGF-R protein expression were linked to mesothelial cells phagocytosing long fibers as observed by phase-contrast microscopy. To determine the importance of EGF-R expression in these cells, we assessed downstream signaling events in rat pleural mesothelial (RPM) cells by looking at the induction of activator protein 1 (AP-I), a transcription factor that controls the transition to S phase in the cell cycle, leading to cell proliferation. Crocidolite induced AP-I in RPM cells in a dose-dependent manner, and this induction of AP-I in RPM cells was inhibited by coincubation with tyrphostin AG 1478, a potent inhibitor of the EGF-R. To examine the mechanism of induction of EGF-R in RPM cells by asbestos, RPM cells were treated with crocidolite in the presence and absence of the antioxidant N acetylcysteine (NAC). Reduced glutathione (GSH) was examined as a marker of oxidative stress and the expression of EGF-R protein was measured. Crocidolite asbestos caused a dose-dependent depletion of GSH in RPM cells, and the presence of NAC ameliorated the expression of EGF-R protein by crocidolite. Our data suggest that carcinogenic fibers induce EGF-R via a mechanism involving oxidative stress initiating cell signaling cascades in mesothelial cells leading to cell proliferation and carcinogenesis. PMID- 26368633 TI - Differential Display Analysis of Fiber-Induced Carcinogenesis in Rat: Clue for Involvement of Integrin-Mediated Signal Transduction. AB - In this study, mRNA expression patterns during mesothelioma carcinogenesis in the peritoneal cavity were investigated. To this purpose, the mRNA expression patterns of fiber-induced mesothelioma and of fiber-treated tissues were compared to untreated tissues, respectively. Suppression subtractive hybridization (SSH) and an array hybridization assay were used to perform differential display analyses. Genes found to be expressed differentially mainly represent proteins of signal transduction pathways and regulatory proteins of the cell cycle. The genes for components of the AP-1 transcription factor, c-jun, c-fos, and fra-1 (fos related antigen-1) are upregulated in nontumorous tissue treated with asbestos. These data confirm in vivo the involvement of AP-I expression as response to fiber treatment. In addition, osteopontin, zyxin, and integrin-linked kinase were upregulated in tumors and in treated tissues. These genes code for proteins involved in the signal transduction from the extracellular matrix to the nucleus. Using integrin-specific inhibitors, the apoptotic effects of crocidolite fibers could be suppressed significantly. From these results we hypothesize that direct effects of the fibers on the target tissue are mediated by interaction of the fibers with the extracellular matrix molecules. PMID- 26368634 TI - Ultrafine Particle-Mediated Activation of Macrophages: Intracellular Calcium Signaling and Oxidative Stress. AB - Various intracellular pathways are known to activate gene expression of proinflammatory mediators such as cytokines; one such pathway involves calcium. Recently we presented data that show that ultrafine (uf) carbon black (CB)(14 nm diameter), but not fine CB (260 nm diameter) is able to induce a 2.6-fold increase in the calcium response to stimulation by thapsigargin in a human macrophage cell line (Mono Mac 6). The present study aimed to investigate whether other uf particles could invoke similar alterations in calcium influx in both macrophage cell lines and primary macrophages. Treatment of MM6 cells with uf latex beads (64 nm diameter) for 1500 s induced a 2.3-fold (p < .01) increase in the response to thapsigargin, whereas fine latex (202 nm diameter) did not have any significant effect. Similarly, in primary rat bronchoalveolar lavage (BAL) cells (>80% macrophages), ufCB (33 MUg/ml, 1500 s) induced a 2.6-fold (p < .001) increase in the response to thapsigargin, whereas fine CB had no significant effect. The effects of ufCB on the enhanced response to thapsigargin in the MM6 cells were significantly attenuated by the antioxidants mannitol (p < .05) and nacystelin, indicating that the effect of ultrafine particles on calcium influx was in part mediated by reactive oxygen species. Support for a role for reactive oxygen species was obtained in MM6 cells using the dye dichlorofluorescin diacetate. Ultrafine latex induced a significant increase in fluorescence of 133.0 +/- 6.5 fluorescence units (p < .001), whereas fine latex did not have any significant effect. In conclusion, effects on calcium fluxes induced by thapsigargin were seen with two very different ultrafine particles - ultrafine latex beads and ultrafine CB-and were seen in both the human MM6 cell line and rat BAL cells. Finally, the induction of an oxidative stress by the ultrafine particles was supported by the ability of ultrafine latex beads to induce ROS production. In addition, ultrafine carbon black was found to induce enhanced calcium influx, partly through oxidative stress. PMID- 26368635 TI - Molecular Activation of Activator Protein-1 In Silica and Asbestos-Induced Carcinogenesis. AB - Occupational exposures to asbestos and crystalline silica have been implicated in causing lung cancer and other pulmonary diseases in humans. Despite intensive research during the last decade on pulmonary carcinogenesis induced by these minerals, the exact molecular mechanisms involved in carcinogenesis are still unknown. Chronic inflammation and enhanced production of reactive oxygen species (ROS) generated by these particulates have been implicated in the development of tumors. In an attempt to understand the molecular basis of carcinogenesis induced by these particles, we investigated the potential activation of activator protein 1 (AP-1) by crocidolite and freshly fractured or aged crystalline silica in a JB6 P(+) cell line stably transfected with AP-1-luciferase reporter plasmid (in vitro) and in AP-1-luciferase reporter transgenic mice (in vivo). This transcription factor governs the expression of target genes that are involved in encoding cytokines, chemokines, growth factors, cell adhesion molecules, and acute-phase proteins that regulate inflammation, cell proliferation, and apoptosis. Results of our studies suggest that asbestos and silica activate AP-1 through generation of ROS. In in vitro studies, crocidolite asbestos caused a dose- and time-dependent AP-1 activation in JB6+ cells, which persisted for at least 72 h. In transgenic mice exposed to crocidolite asbestos, AP-1 activation increased significantly by 10-fold in lung tissue and 22-fold in bronchial tissue. This induction of AP-1 activation by crocidolite appears to be mediated through the influence of mitogen-activated protein kinase (MAPK) family members, specifically extracellular signal-regulating protein kinase, ERK 1, and ERK 2 (data not presented). Similarly, freshly fractured silica caused an 8-fold increase in AP-1 activation in JB6 P+cells and 22-fold increase in transgenic mice. The activation of AP-1 by freshly fractured silica was mediated through ERK1, ERK2, and p38 kinase. Activation of AP-1 by asbestos or silica was inhibited in both in vitro and in vivo systems by aspirin, which exhibits OH radical scavenging properties. It is proposed from these studies that asbestos and crystalline silica may promote carcinogenesis through specific mechanistic pathways stimulated by ROS. PMID- 26368636 TI - Activation of Transcription Factors by Diesel Exhaust Particles in Human Bronchial Epithelial Cells in Vitro. AB - Diesel exhaust particles (DEP) are suspected to be involved in the aggravation of inflammatory respiratory diseases. We have shown previously, in human bronchial epithelial cell line 16HBE 14o-, that DEP induced the release of the proinflammatory cytokines granulocyte-macrophage colony-stimulating factor (GM CSF) and interleukin-8 (IL-8) after 24 h of exposure. Gene expression of these cytokines is regulated by transcription factors including NF-kappaB and AP-1, which are known to be sensitive to oxidative stress. Their activation by DEP was investigated in comparison with a pure oxidant, H2O2 A 4-h exposure to DEP (10 MUg/cm(2)) or to H2O2 (100 uM) increased NF-kappaB DNA binding in 16HBE cells as assessed by electrophoretic mobility shift assay. AP-1 was only activated by H202 in the same conditions. Organic extracts of DEP increased NF-kappaB DNA binding as did native DEP, suggesting the role of the polycyclic aromatic hydrocarbons (PAH) in this NF-kappaB increased DNA binding. Dimethylthiourea (DMTU), an antioxidant, inhibited the NF-kappaB DNA binding induced by DEP, suggesting an involvement of reactive oxygen species (ROS) in the transduction pathways leading to NF-kappaB activation. Moreover, the MEK pathway inhibitor PD98059 inhibited DEP-induced NF-kappaB DNA binding. The role of Erk 1/2 was likely implicated, since DEP induced an increase of Erk phosphorylation. PMID- 26368637 TI - IgE Adjuvant Activity of Particles-What Physical Characteristics are Important? AB - Diesel exhaust particles (DEP) are reported to increase the allergic immune response to ovalbumin (OVA) and pollen. There are studies reporting that both the adsorbed chemical substances and the carbon core of DEP may contribute to the immunoglobulin E (IgE) adjuvant effect. The aim of this study was to investigate which physical properties of particles per se, that is, the particles by themselves, might be important for their IgE adjuvant effect, namely, dose weight, size, number, and surface area. Since DEP have a tendency to form aggregates of varying shapes and sizes, evaluation of the relative importance of these characteristics is difficult using DEP. We therefore decided to use well characterized, spherical polystyrene particles (PSP). We performed four different types of experiments, in which the total dose weight (12.25 mg), size (0.1 MUm in diameter), total number (8 x 10(10)), or total surface area (1300 cm(2)) of PSP, respectively, was kept constant. NIH/Ola mice were given 2 intraperitoneal injections with PSP plus OVA or OVA alone, over a 16-day period. The mice were exsanguinated at the end of each experiment, and the serum concentration of IgE anti-OVA was measured. The serum levels of IgE anti-OVA increased with both an increasing number and surface area of PSP. We found no clear association between PSP size and the levels of IgE anti-OVA, but because of the relatively small size range of PSP used, no definitive conclusions can be made on whether size is an important factor for the IgE adjuvant effect of PSP. There seemed to be no covariation between the dose weight and the levels of IgE anti-OVA. Our findings indicate that the total number and total surface area of PSP, rather than the dose weight, are important parameters for the IgE adjuvant activity from PSP, and possibly also for particles in general. PMID- 26368638 TI - Enhanced Allergic Sensitization in Animals Exposed to Particulate Air Pollution. AB - Epidemiological studies have found an association between elevated levels of particulate matter (PM) air pollution and increased medication use and hospital visits by asthmatics. While it is known that asthmatics are generally more sensitive to airborne contaminants such as sulfur dioxide and tobacco smoke, it is difficult to test which components of air pollution may also contribute to the induction of pulmonary allergy (sensitization) because of the risk in creating disease. Recent studies in mice and rats, however, have demonstrated that pulmonary exposure to combustion particles such as diesel and residual oil fly ash (ROFA) can exacerbate immunological sensitization (in the form of immunoglobulin E antibody and lymphocyte reactivity) to experimental and natural allergens. Subsequent allergen challenge in these animals results in a greater allergen-induced bronchoconstriction, elevated numbers of eosinophils in the lung, and enhanced airway responsiveness to cholinergic agents compared to what occurs in similarly immunized animals pretreated with vehicle or "inert" particles. Although the mechanisms for these effects are not known, it has been demonstrated that the adjuvant effects of diesel and ROFA can be reproduced with hydrocarbons and soluble transition metals from diesel and ROFA, respectively. In addition, analysis of mediator expression and release over the sensitization phase has revealed that PM exposure can enhance production of Th2 cytokines such as interleukin-5 (IL-5) and the proinflammatory cytokine tumor necrosis factor alpha (TNF-alpha). These experimental systems demonstrate the potential of particulate air pollutants to enhance allergic sensitization and can be further used to elucidate the mechanism for these effects. PMID- 26368639 TI - Time Course of Eosinophilic Recruitment and Pulmonary Toxicity Biomarkers in an Allergic Asthma Model in Brown Norway Rats. AB - Allergic asthma is a pulmonary disease characterized by antigen-induced pulmonary eosinophilia, airway hyperresponsiveness, antigen-specific IgE antibody responses, and broncho-constriction. In attempting to elucidate mechanisms associated with the pathogenesis of this disease, a number of animal models have been developed. The current studies were undertaken to develop a model of allergic asthma model in Brown Norway rats. Unlike the neutrophilic inflammatory response to inhaled particles in most strains of rats, inhalation of antigens in sensitized Brown Norway rats results in a complex cellular response which is characterized by a variety of inflammatory cell types, and is dependent on the time course of inflammatory cell recruitment. In characterizing this ovalbumin challenge model of allergic asthma, it was important to assess the time course of pulmonary inflammation, cell proliferation, and apoptosis. Male Brown Norway rats were sensitized and boosted with intraperitoneal injections of ovalbumin in aluminum hydroxide on experimental days 1 and 8. On days 15-17, rats were challenged by an inhalation exposure to 5% ovalbumin and were evaluated by bronchoalveolar lavage (BAL) at 24 or 48 h postexposure (PE). Control rats were similarly treated to ovalbumin aerosol exposures; however, these animals had been sensitized and boosted with aluminum hydroxide (minus the ovalbumin). Cell differential evaluations demonstrated that the rats exposed for 3 days/24 h postexposure and for 2 days/ 48 h postexposure produced the greatest numbers of BAL eosinophils and corresponding indicators of pulmonary toxicity. It was interesting to note that earlier exposure time periods (i.e., 1 day/24 h PE) generated a predominantly neutrophilic inflammatory response, while longer exposure/postexposure time periods (i.e., 3 days/48 h) produced a predominant mononuclear inflammatory response. Subsequent studies demonstrated that the 2 day/ 48-h protocol produced the optimum eosinophilic, cytotoxic, cell proliferative, and apoptotic response. Histopathological evaluations demonstrated a chronically active alveolitis and bronchiolitis, characterized by epithelial cell proliferation in the airways and inflammatory cell proliferation in the alveoli. Studies are ongoing to assess the cell types undergoing apoptosis in both the airway and parenchymal regions to fully characterize this model in order to assess its relevance and utility for studying asthma in humans. PMID- 26368640 TI - Dosimetry of Particles: Critical Factors Having Risk Assessment Implications. AB - Species differences in the handling of particles are topics of interest for setting ambient particulate matter standards as well as for studies involving the phenomenon of lung overload and the implications, if any, of such studies for workplace dust exposure standards. The dosimetry of inhaled particles differs among the three major regions of the respiratory tract (extrathoracic, tracheobronchial, and pulmonary). Particulate dosimetry includes both deposition, which is the process of removing particles from inhaled air to various locations in the respiratory tract during breathing, and clearance, which refers to the rates and routes by which deposited particles are removed from the respiratory tract. Species-specific structure of respiratory-tract regions combines with the route and depth of breathing to greatly influence where particles deposit. The dominant mechanisms for deposition and clearance of inhaled particles differ by region. Inertial impaction is important for head deposition in humans of large particles and for tracheobronchial deposition of particles larger than about 2.5 MUm in aerodynamic diameter. Enhanced head deposition of ultrafine particles due to diffusion occurs in both laboratory animals and humans since nasal turbinate surfaces are large compared with the cross-sectional area and are in close proximity to the airstream. Deposition in the tracheobronchial region of rats is due to impaction and sedimentation mechanisms for particles larger than about MUm in aerodynamic diameter. Factors such as inhalability, oronasal breathing, and heterogeneity in tracheobronchial path length and acinar volume affect the deposition of particles in laboratory animals and humans to differing degrees. While particles less than 5 MUm in aerodynamic diameter are completely inhalable by humans, inhalability in rats decreases from 97 to 65% as aerodynamic particle size increases from 0.5 to 5 MUm. Rats are obligate nasal breathers, but humans switch to oronasal breathing when work or exercise requires a minute ventilation that exceeds about 35 L/min. This species difference has significant implications for particulate risk assessments. The monopodial branching system of the tracheobronchial airways of rats compared with bipodial or tripodial branching in humans can impart significant intra- and interspecies heterogeneity in the deposition of particles in the alveolar region. Clearance mediated by alveolar macrophages (AM) is an important factor in lung overload phenomena associated with chronic studies in rodents of poorly soluble particles. Data presented on AM characteristics across species support the notion that various dose metrics need to be examined that may better reflect critical steps in the process of lung overload. PMID- 26368641 TI - Evaluation of Particle Clearance and Retention Kinetics in the Lungs of U.S. Coal Miners. AB - Rodent studies are frequently used to assess risk in humans, yet it is not known whether the overloading of lung clearance, as observed in rodents, occurs in humans, or whether overloading is related to particle-related lung diseases in humans. The objective of this study is to develop a biologically based mathematical model to describe the retention and clearance of respirable coal mine dust in the lungs of humans. A human dosimetric lung model was developed that includes alveolar, interstitial, and hilar lymph-node compartments. The model describes the particle mass transfer kinetics among these compartments and clearance via the tracheobronchi. The model was calibrated using data in U.S. coal miners, including individual working lifetime exposure histories and lung and lymph-node particle burdens. The model fit to the human data was evaluated using a least-squared error criterion. The end-of-life lung dust burdens of all coal miners in this study were substantially greater than expected from a simple, linear first-order model with effective clearance, yet their lung and lymph-node dust burdens were lower than expected from the rodent-based overload model, particularly at higher exposures. The best fitting model included a predominant first-order interstitial compartment, in which the particles are essentially sequestered (with very slow clearance to the lymph nodes), and a first-order alveolar clearance compartment with either no dose-dependent decline (overloading) or much less than expected from the rodent studies. These findings are consistent with the findings from magnetopneumography studies of clearance in retired miners and from studies of particle retention patterns in rodents and primates. This human dosimetric lung model is useful for evaluating the kinetic differences of particle retention in humans and rodents, and for evaluating the lung closes in humans given different exposure scenarios. PMID- 26368642 TI - Mathematical Modeling to Predict the Responses to Poorly Soluble Particles in Rat Lungs. AB - Rat inhalation experiments with titanium dioxide (TiO2) and barium sulfate (BaSO4), at concentrations calculated to produce similar volumetric lung burden for both dusts, showed overload with TIO2 but not for BaSO4 "Overload," occurring in rats exposed to "low-toxicity" dusts at high concentrations, is characterized by a rapid deterioration in clearance and onset of inflammation. Impairment of alveolar macrophage (AM) mediated clearance, dust translocation to the lymph nodes, and neutrophil (PMN) recruitment for both dusts were better predicted by the lung burden expressed as surface area rather than mass or volume. A mathematical model describing the translocation (in terms of particulate mass) of inhaled particles in various physiologically based pulmonary compartments was used to calculate pulmonary clearance when effective and also when impairment by overload leads to increased dust translocation to the lymph nodes. Our objectives were: (I) to modify this model to include the influence of particle surface area on clearance and interstitialization; (2) to extend the model to describe the PMN recruitment; and (3) to use the model to estimate the highest exposure level such that overload would be avoided in a chronic inhalation experiment with rats. In extrapolating down to no-overload concentrations, due account was taken of the observed interanimal variation (assuming this variation was mainly due to differences in inhaled dose). For TiO2 and BaSO4, with the given size distributions, the predicted concentrations at which 95% of the animals were expected to avoid overload were 3 mg m(-3) and 7.5 mg m(-3), respectively. The general quantitative relationships on the role of particle surface area and on the estimation of the no-overload level have important implications for setting standards for poorly soluble particles. PMID- 26368643 TI - Asbestos Fiber Type and Length in Lungs of Chrysotile Textile and Production Workers: Fibers Longer than 18 MUm. AB - Excess lung cancer risk for a cohort of chrysotile textile plant workers was many times the risk observed in a cohort of chrysotile miners/millers. The latter had greater exposure to chrysotile/tremolite. A previous lung burden study confirmed this excess exposure in miners/millers and showed little difference in fiber length. Selection of too short a fiber length cut-off (5 um or more) in the previous study could have masked differences in lung-retained fiber length. In this follow-up, we counted only those intrapulmonary fibers exceeding 18 um in length. Lung fiber concentration and dimension were assessed by transmission electron microscopy (TEM) and energy-dispersive x-ray spectrometry (EDS) for autopsy samples from 64 textile workers and 43 chrysotile miners and millers. These long fibers were significantly more concentrated in the lungs of chrysotile miners and millers, consistent with their greater exposure. However, when only these longest fibers were compared, there was a somewhat greater mean and median intrapulmonary fiber length for chrysotile textile workers (mean fiber length, all fiber types combined, 25.2 +/- 10.2 um vs. 22.9 +/- 6.6 um in miners/millers, < .001; medians 21.6 vs. 20, p < .05). Despite their lesser apparent lung cancer risk, chrysotile, tremolite, total amphibole, and total long fiber asbestos concentrations were all highest in the lungs of miners/millers. Twenty-two of 64 textile workers had lung content of crocidolite and/or amosite (32.5% of 508). These amosite/crocidolite fibers were present in the lungs of workers who ceased employment prior to the first use of such fibers recorded in this industry. The results suggest that (I) asbestos fiber length differences cannot explain the difference in lung cancer risk excess and slope between cohorts and (2) the experience of textile workers should not be used to assess risk of lung cancer in miners, cement workers, and friction product workers, regardless of fiber type. PMID- 26368644 TI - The Necessity of Developing New Criteria for Carcinogen Classification of Fibers by the Mak Commission. AB - The criteria for carcinogen classification of critical man-made mineral fibers (MMMF) by the MAK Commission are presently based on carcinogenicity and genotoxicity data. This classification is based on qualitative criteria. The MAK Commission considers all inorganic fibers and fibrous dust particles with a ratio of length to diameter greater than 3:1 and that are longer than 5 um and have a diameter less than 3 um to be potential carcinogens (category 3) (DFG, 1998; Creim, 1997). For chemicals in general, the MAK Commission has supplemented the three previously used categories "carcinogenic to humans," "carcinogenic to animals," and "suspected of having carcinogenic potential" with two additional categories. Chemicals that act primarily by nongenotoxic mechanisms and for which evaluation of low-dose exposure is possible are classified in category 4. Cenotoxic carcinogens for which risk at low doses can be assessed are classified in category 5. The essential feature of these two categories is that exposure at the workplace up to a given limit (MAK value) does not contribute significantly to the risk of cancer in humans. Thus, for classification of fibers into category 4 or 5, the evaluation of primary or secondary genotoxic effects is required. For the establishment of an MAK value for fibers, the identification of a no-observed effect level (NOFL) representing a steady state of fiber uptake and elimination is necessary. Early inflammatory responses associated with changes in the parameters of bronchoalveolar lavage and cell proliferation in lung tissue are considered sensitive parameters for identifying the NOEL. Data on biopersistence under exposure conditions that prevent particle accumulation exceeding the steady state conditions of the NOEL are required in order to consider the potential of fiber accumulation as an inherent fiber property including fiber dissolution and fiber disintegration. It is therefore necessary that the design of testing strategies to evaluate toxicity and carcinogenicity of fibers include dose response studies to identify the NOEL of the most sensitive endpoint, such as by analysis of parameters of lung lavage, histopathol-ogy, and determination of biopersistence. Further, a basic understanding of the underlying genotoxic mechanisms is required for differentiation between primary and secondary mechanisms and their dose dependence. PMID- 26368645 TI - Preface. PMID- 26368646 TI - Langerhans cell sarcoma with lineage infidelity/plasticity: a diagnostic challenge and insight into the pathobiology of the disease. AB - Langerhans cell sarcoma is a very rare and aggressive tumor of Langerhans cell lineage, for which aberrant expression of T-cell-related antigens has not yet been reported in a primary skin tumor. The authors describe the first known case of a primary cutaneous Langerhans cell sarcoma with lineage infidelity and use comparative genomic hybridization to investigate the genetic composition of the tumor and detect DNA copy number alterations throughout its entire genome. The case involves a 62-year-old woman who presented with an irregular nodule on the forehead surrounded by smaller lesions in its vicinity. The clinical impression was melanoma with satellitosis. The biopsy specimen showed an epidermotropic tumor with moderate-to-marked cellular pleomorphism and significantly increased mitotic rate but no necrosis. The immunoprofile of the lesion was remarkable, as next to common Langerhans cell markers: Langerin, CD1a, S100, and CD4; it also exhibited an aberrant T-cell phenotype with the expression of CD2, CD3, and CD43. In addition, fascin and CD30 were also expressed, further exaggerating potential diagnostic pitfalls. Langerhans cell lineage was confirmed by the demonstration of characteristic Birbeck granules on electron microscopy. Whole genome analysis for copy number changes and loss of heterozygosity showed a complex karyotype with variable hyperdiploidy and numerous allelic imbalances. Significant findings included a homozygous deletion at 9p21 involving the CDKN2A and loss of heterozygosity at 17p involving TP53 gene, coupled with a TP53 missense mutation. Despite reexcision and multiagent systemic chemotherapy, the patient died of metastasis 2 years after diagnosis. This case is an outstanding example of lineage infidelity in a hematologic malignancy and the utilization of comparative genomic hybridization in characterizing its genetic abnormalities. PMID- 26368647 TI - Clinicopathologic Features of Hydroa Vacciniforme-Like Lymphoma: A Series of 9 Patients. AB - Hydroa vacciniforme-like lymphoma is a recently recognized cutaneous T-cell lymphoma associated with Epstein-Barr virus. The disease is observed in children of Latin American or Asian ethnicity. The authors report the clinical, histopathological, and immunophenotypical features of 9 new Mexican patients (M:F = 2:1; mean age, 14.5 years; median age, 13.3 years; age range, 4-27 years), expanding on previous observations of this elusive disease. The most common clinical aspects were persistent facial edema with necroses and pitted scars. Histopathological analyses revealed variably dense lymphoid infiltrates with common angiodestructive features. Neoplastic cells expressed CD3 and cytotoxic markers in all cases and were constantly positive for Epstein-Barr virus (EBER 1). Expression of other markers was variable. Follow-up data revealed that all patients died within 6 months or less, thus showing a very aggressive course with poor prognosis. PMID- 26368648 TI - Transmucosal Immediate-Release Fentanyl for Breakthrough Cancer Pain: Opportunities and Challenges for Use in Palliative Care. AB - Opioids are used to treat breakthrough cancer pain (BTCP) and can be classified by relative duration and onset of action. Regulatory approvals of numerous transmucosal immediate-release fentanyl (TIRF) formulations provide alternative options to palliative care-trained providers in the management of BTCP. TIRFs have been formulated as a sublingual tablet, sublingual spray, intranasal spray, pectin-based nasal spray, buccal tablet, and buccal soluble film. Differences exist between TIRFs regarding formulation design and dosing to treat BTCP. Opportunities for use include palliation of BTCP in head and neck cancer and/or radiation-induced mucositis. The purpose of this review is to discuss TIRF formulation and dosing, pharmacokinetics, clinical efficacy, patient acceptability, and safety/tolerability. In addition, barriers to TIRF utilization will be discussed. PMID- 26368649 TI - Aza-Glycine Induces Collagen Hyperstability. AB - Hydrogen bonding is fundamental to life on our planet, and nature utilizes H bonding in nearly all biomolecular interactions. Often, H-bonding is already maximized in natural biopolymer systems such as nucleic acids, where Watson-Crick H-bonds are fully paired in double-helical structures. Synthetic chemistry allows molecular editing of biopolymers beyond nature's capability. Here we demonstrate that substitution of glycine (Gly) with aza-glycine in collagen may increase the number of interfacial cross-strand H-bonds, leading to hyperstability in the triple-helical form. Gly is the only amino acid that has remained intolerant to substitution in collagen. Our results highlight the vital importance of maximizing H-bonding in higher order biopolymer systems using minimally perturbing alternatives to nature's building blocks. PMID- 26368650 TI - Neurogranin Levels in Cerebrospinal Fluid: A New Addition to the Alzheimer Disease Diagnostic Toolbox. PMID- 26368651 TI - Physiological and Biochemical Changes Imposed by CeO2 Nanoparticles on Wheat: A Life Cycle Field Study. AB - Interactions of nCeO2 with plants have been mostly evaluated at seedling stage and under controlled conditions. In this study, the effects of nCeO2 at 0 (control), 100 (low), and 400 (high) mg/kg were monitored for the entire life cycle (about 7 months) of wheat plants grown in a field lysimeter. Results showed that at high concentration nCeO2 decreased the chlorophyll content and increased catalase and superoxide dismutase activities, compared with control. Both concentrations changed root and leaf cell microstructures by agglomerating chromatin in nuclei, delaying flowering by 1 week, and reduced the size of starch grains in endosperm. Exposed to low concentration produced embryos with larger vacuoles, while exposure to high concentration reduced number of vacuoles, compared with control. There were no effects on the final biomass and yield, Ce concentration in shoots, as well as sugar and starch contents in grains, but grain protein increased by 24.8% and 32.6% at 100 and 400 mg/kg, respectively. Results suggest that more field life cycle studies are needed in order to better understand the effects of nCeO2 in crop plants. PMID- 26368652 TI - Determinants and challenges in physical activity participation in families with children with high functioning autism spectrum disorders from a family systems perspective. AB - The underlying factors affecting physical activity (PA) participation of children with high-functioning autism spectrum disorders (HFASDs) and their family members were investigated using a mixed method research design. Six families with children with HFASD aged 4 through 13 participated in the study. Findings revealed that levels of moderate to vigorous physical activity (MVPA) in children with HFASD varied between 85 min and 405 min for seven days. Parents of children with HFASD in this study were inactive (levels of MVPA varied between 6 min and 53 min) during this period. Qualitative data from parents highlighted many essential issues. Those issues are categorized under three main themes: (a) understanding PA in children with HFASD, (b) living with a child with HFASD, and (c) awareness of autism spectrum disorders (ASD) at school and community settings. Social skills, issues related to bullying, fear of injury to the child, as well as support from family members and lack of understanding of the disability emerged as subthemes extracted from these data. PMID- 26368653 TI - Circulating Dendritic Cells, Farm Exposure and Asthma at Early Age. AB - Farm environment has been shown to protect from childhood asthma. Underlying immunological mechanisms are not clear yet, including the role of dendritic cells (DCs). The aim was to explore whether asthma and farm exposures are associated with the proportions and functional properties of DCs from 4.5-year-old children in a subgroup of the Finnish PASTURE birth cohort study. Myeloid DCs (mDCs), plasmacytoid DCs (pDCs) and CD86 expression on mDCs ex vivo (n = 100) identified from peripheral blood mononuclear cells (PBMCs) were analysed using flow cytometry. MDCs and production of interleukin (IL)-6 and tumour necrosis factor alpha (TNF-alpha) by mDCs were analysed after 5 h in vitro stimulation with lipopolysaccharide (LPS) (n = 88). Prenatal and current farm exposures (farming, stables, hay barn and farm milk) were assessed from questionnaires. Asthma at age 6 years was defined as a doctor's diagnosis and symptoms; atopic sensitization was defined by antigen-specific IgE measurements. Asthma was positively associated with CD86 expression on mDCs ex vivo [adjusted odds ratio (aOR) 4.83, 95% confidence interval (CI) 1.51-15.4] and inversely with IL-6 production in mDCs after in vitro stimulation with LPS (aOR 0.19, 95% CI 0.04-0.82). In vitro stimulation with LPS resulted in lower percentage of mDCs in the farm PBMC cultures as compared to non-farm PBMC cultures. Our results suggest an association between childhood asthma and functional properties of DCs. Farm exposure may have immunomodulatory effects by decreasing mDC proportions. PMID- 26368655 TI - Role of the planar cell polarity gene Protein tyrosine kinase 7 in neural tube defects in humans. AB - BACKGROUND: Neural tube defects (NTDs) are among the most common congenital defects affecting approximately 1 in 1000 live births in North America. Their etiology is complex including environmental and genetic factors. Defects in the planar cell polarity (PCP) signaling pathway have been strongly associated with NTDs in animal models and human cohorts. Protein tyrosine kinase 7 (Ptk7) was shown to cause a very severe form of NTDs called craniorachischisis in a mouse model and genetically interacts with a core PCP member Vangl2 where double heterozygotes suffer from spina bifida. In this study, we examined the role of PTK7 in human NTDs to determine whether variants at this gene predispose to these defects. METHODS: We sequenced the coding region and the exon-intron junctions of PTK7 in a cohort of 473 patients affected with various forms of open and closed NTDs. Novel and rare variants(<1%) were genotyped in a cohort of 473 individuals. Their pathogenic effect was predicted in silico and functionally in an overexpression assay in a well-established zebrafish model. RESULTS: We identified in our cohort 6 rare variants, 3 of which were absent in public databases. One variant, p.Gly348Ser, acted as a hypermorph when overexpressed in the zebrafish model. CONCLUSION: We detected potentially pathogenic PTK7 variants in 1.1% of our NTD cohort. Our findings implicate PTK7 as a risk factor for NTDs and provide additional evidence for a pathogenic role of PCP signaling in these malformations. PMID- 26368654 TI - The omniscient placenta: Metabolic and epigenetic regulation of fetal programming. AB - Fetal development could be considered a sensitive period wherein exogenous insults and changes to the maternal milieu can have long-term impacts on developmental programming. The placenta provides the fetus with protection and necessary nutrients for growth, and responds to maternal cues and changes in nutrient signaling through multiple epigenetic mechanisms. The X-linked enzyme O linked-N-acetylglucosamine transferase (OGT) acts as a nutrient sensor that modifies numerous proteins to alter various cellular signals, including major epigenetic processes. This review describes epigenetic alterations in the placenta in response to insults during pregnancy, the potential links of OGT as a nutrient sensor to placental epigenetics, and the implications of placental epigenetics in long-term neurodevelopmental programming. We describe the role of placental OGT in the sex-specific programming of hypothalamic-pituitary-adrenal (HPA) axis programming deficits by early prenatal stress as an example of how placental signaling can have long-term effects on neurodevelopment. PMID- 26368657 TI - Circular Halbach array for fast magnetic separation of hyaluronan-expressing tissue progenitors. AB - Connective tissue progenitors (CTPs) are a promising therapeutic agent for bone repair. Hyaluronan, a high molecular mass glycosaminoglycan, has been shown by us to be a suitable biomarker for magnetic separation of CTPs from bone marrow aspirates in a canine model. For the therapy to be applicable in humans, the magnetic separation process requires scale-up without compromising the viability of the cells. The scaled-up device presented here utilizes a circular Halbach array of diametrically magnetized, cylindrical permanent magnets. This allows precise control of the magnetic field gradient driving the separation, with theoretical analysis favoring a hexapole field. The separation vessel has the external diameter of a 50 mL conical centrifuge tube and has an internal rod that excludes cells from around the central axis. The magnet and separation vessel (collectively dubbed the hexapole magnet separator or HMS) was tested on four human and four canine bone marrow aspirates. Each CTP-enriched cell product was tested using cell culture bioassays as surrogates for in vivo engraftment quality. The magnetically enriched cell fractions showed statistically significant, superior performance compared to the unenriched and depleted cell fractions for all parameters tested, including CTP prevalence (CTPs per 10(6) nucleated cells), proliferation by colony forming unit (CFU) counts, and differentiation by staining for the presence of osteogenic and chondrogenic cells. The simplicity and speed of the HMS operation could allow both CTP isolation and engraftment during a single surgical procedure, minimizing trauma to patients and lowering cost to health care providers. PMID- 26368656 TI - How to resolve microsecond current fluctuations in single ion channels: the power of beta distributions. AB - A main ingredient for the understanding of structure/function correlates of ion channels is the quantitative description of single-channel gating and conductance. However, a wealth of information provided from fast current fluctuations beyond the temporal resolution of the recording system is often ignored, even though it is close to the time window accessible to molecular dynamics simulations. This kind of current fluctuations provide a special technical challenge, because individual opening/closing or blocking/unblocking events cannot be resolved, and the resulting averaging over undetected events decreases the single-channel current. Here, I briefly summarize the history of fast-current fluctuation analysis and focus on the so-called "beta distributions." This tool exploits characteristics of current fluctuation-induced excess noise on the current amplitude histograms to reconstruct the true single channel current and kinetic parameters. A guideline for the analysis and recent applications demonstrate that a construction of theoretical beta distributions by Markov Model simulations offers maximum flexibility as compared to analytical solutions. PMID- 26368658 TI - Physiological analyses indicate superoxide dismutase, catalase, and phytochelatins play important roles in Pb tolerance in Eremochloa ophiuroides. AB - Phytoremediation is considered to be a promising approach to restore or stabilize soil contaminated by lead (Pb). Turfgrasses, due to their high biomass yields, are considered to be suitable for use in phytoextraction of soil contaminated with heavy metal. It has been demonstrated that centipedegrass (Eremochloa ophiuroides (Munro) Hack., Poaceae) is a good turfgrass for restore of soil contaminated by Pb. However, the enhanced tolerant mechanisms in metallicolous (M) centipedegrass accessions remain unknown. In this study, we made a comparative study of growth performance, Pb accumulation, antioxidant levels, and phytochelatin concentrations in roots and shoots from M and nonmetallicolous (NM) centipedegrass accessions. Results showed that turf quality and growth rate were less repressed in M accessions than in NM accession. Pb stress caused generation of reactive oxygen species in centipedegrass with relatively lower levels in M accessions. Antioxidant activity analysis indicated that superoxide dismutase and catalase played important roles in Pb tolerance in M accessions. M accessions accumulated more Pb in roots and shoots. Greatly increased phytochelatins and less repressed sulfur contents in roots and shoots of M accessions indicated that they correlated with Pb accumulation and tolerance in centipedegrass. PMID- 26368660 TI - Preparation and evaluation of a timolol maleate drug-resin ophthalmic suspension as a sustained-release formulation in vitro and in vivo. AB - The aim of this work was to assess the performance of resin as an ocular delivery system. Timolol maleate (TM) was chosen as the model drug and an ion exchange resin (IER) as the carrier. The drug-resin complex was prepared using an oscillation method and then characterized regarding particle size, zeta potential, morphology, and drug content. After in vitro drug release study and corneal permeation study were performed, in vivo studies were performed in New Zealand albino rabbits using a suspension with particles sized 4.8 +/- 1.2 MUm and drug loading at 43.00 +/- 0.09%. The results indicate that drug released from the drug-resin ophthalmic suspension permeated the cornea and displayed a sustained-release behavior. Drug levels in the ocular tissues after administration of the drug-resin ophthalmic suspension were significantly higher than after treatment with an eye drop formulation but were lower in body tissues and in the plasma. In conclusion, resins have great potential as effective ocular drug delivery carriers to increase ocular bioavailability of timolol while simultaneously reducing systemic drug absorption. PMID- 26368659 TI - Identification of infants at high-risk for autism spectrum disorder using multiparameter multiscale white matter connectivity networks. AB - Autism spectrum disorder (ASD) is a wide range of disabilities that cause life long cognitive impairment and social, communication, and behavioral challenges. Early diagnosis and medical intervention are important for improving the life quality of autistic patients. However, in the current practice, diagnosis often has to be delayed until the behavioral symptoms become evident during childhood. In this study, we demonstrate the feasibility of using machine learning techniques for identifying high-risk ASD infants at as early as six months after birth. This is based on the observation that ASD-induced abnormalities in white matter (WM) tracts and whole-brain connectivity have already started to appear within 24 months after birth. In particular, we propose a novel multikernel support vector machine classification framework by using the connectivity features gathered from WM connectivity networks, which are generated via multiscale regions of interest (ROIs) and multiple diffusion statistics such as fractional anisotropy, mean diffusivity, and average fiber length. Our proposed framework achieves an accuracy of 76% and an area of 0.80 under the receiver operating characteristic curve (AUC), in comparison to the accuracy of 70% and the AUC of 70% provided by the best single-parameter single-scale network. The improvement in accuracy is mainly due to the complementary information provided by multiparameter multiscale networks. In addition, our framework also provides the potential imaging connectomic markers and an objective means for early ASD diagnosis. PMID- 26368662 TI - Right perceptual bias and self-face recognition in individuals with congenital prosopagnosia. AB - The existence of a drift to base judgments more on the right half-part of facial stimuli, which falls in the observer's left visual field (left perceptual bias (LPB)), in normal individuals has been demonstrated. However, less is known about the existence of this phenomenon in people affected by face impairment from birth, namely congenital prosopagnosics. In the current study, we aimed to investigate the presence of the LPB under face impairment conditions using chimeric stimuli and the most familiar face of all: the self-face. For this purpose we tested 10 participants with congenital prosopagnosia and 21 healthy controls with a face matching task using facial stimuli, involving a spatial manipulation of the left and the right hemi-faces of self-photos and photos of others. Even though congenital prosopagnosics performance was significantly lower than that of controls, both groups showed a consistent self-face advantage. Moreover, congenital prosopagnosics showed optimal performance when the right side of their face was presented, that is, right perceptual bias, suggesting a differential strategy for self-recognition in those subjects. A possible explanation for this result is discussed. PMID- 26368661 TI - Use of pooled samples to assess human exposure to parabens, benzophenone-3 and triclosan in Queensland, Australia. AB - Parabens, benzophenone-3 and triclosan are common ingredients used as preservatives, ultraviolet radiation filters and antimicrobial agents, respectively. Human exposure occurs through consumption of processed food and use of cosmetics and consumer products. The aim of this study was to provide a preliminary characterisation of exposure to selected personal care product chemicals in the general Australian population. De-identified urine specimens stratified by age and sex were obtained from a community-based pathology laboratory and pooled (n=24 pools of 100). Concentrations of free and total (sum of free plus conjugated) species of methyl, ethyl, propyl and butyl paraben, benzophenone-3 and triclosan were quantified using isotope dilution tandem mass spectrometry; with geometric means 232, 33.5, 60.6, 4.32, 61.5 and 87.7ng/mL, respectively. Age was inversely associated with paraben concentration, and females had concentrations approximately two times higher than males. Total paraben and benzophenone-3 concentrations are significantly higher than reported worldwide, and the average triclosan concentration was more than one order of magnitude higher than in many other populations. This study provides the first data on exposure of the general Australian population to a range of common personal care product chemical ingredients, which appears to be prevalent and warrants further investigation. PMID- 26368663 TI - Remifentanil Requirement for Inhibiting Responses to Tracheal Intubation and Skin Incision Is Reduced in Patients With Parkinson's Disease Undergoing Deep Brain Stimulator Implantation. AB - BACKGROUND: Parkinson's disease (PD) is a common neurodegenerative disease affecting the quality of life in the elderly. We speculated that PD patients might have abnormal pharmacodynamics due to the degenerative neural system, and the present study was performed to investigate the pharmacodynamics of remifentanil in PD patients. MATERIALS AND METHODS: Two arms of patients were recruited, including 31 PD patients undergoing pulse generator placement after deep brain stimulator implantation and 31 pair-controlled patients undergoing intracranial surgery without PD (NPD). Patients were anesthetized with target controlled infusion of propofol and remifentanil. The effective concentration of remifentanil to inhibit responses to intubation and skin incision in 50% and 95% patients (EC50 and EC95) was determined by the up and down method. RESULTS: Demographic data, bispectral index, and hemodynamic values were similar between the PD and the NPD groups. The average remifentanil concentration used in the PD group for tracheal intubation is significantly lower than in the NPD group (P<0.001). The EC50 for inhibiting the response to tracheal intubation were 1.86 ng/mL (95% confidential interval [CI], 1.77-1.96 ng/mL) in the PD group and 3.20 ng/mL (95% CI, 3.13-3.27 ng/mL) in the NPD group. The average remifentanil concentration used in the PD group for skin incision is significantly lower than in the NPD group (P<0.001). EC50 for inhibiting the response to skin incision were 2.17 ng/mL (95% CI, 2.09-2.25 ng/mL) in the PD group and 3.09 ng/mL (95% CI, 3.02-3.17 ng/mL) in the NPD group. CONCLUSIONS: The remifentanil concentrations required for inhibiting responses to tracheal intubation and skin incision are reduced markedly in PD patients undergoing pulse generator placement (NCT01992692). PMID- 26368664 TI - Challenges in the Anesthetic and Intensive Care Management of Acute Ischemic Stroke. AB - Acute ischemic stroke (AIS) is a devastating condition with high morbidity and mortality. In the past 2 decades, the treatment of AIS has been revolutionized by the introduction of several interventions supported by class I evidence-care on a stroke unit, intravenous tissue plasminogen activator within 4.5 hours of stroke onset, aspirin commenced within 48 hours of stroke onset, and decompressive craniectomy for supratentorial malignant hemispheric cerebral infarction. There is new class I evidence also demonstrating benefits of endovascular therapy on functional outcomes in those with anterior circulation stroke. In addition, the importance of the careful management of key systemic physiological variables, including oxygenation, blood pressure, temperature, and serum glucose, has been appreciated. In line with this, the role of anesthesiologists and intensivists in managing AIS has increased. This review highlights the main challenges in the endovascular and intensive care management of AIS that, in part, result from the paucity of research focused on these areas. It also provides guidelines for the management of AIS based upon current evidence, and identifies areas for further research. PMID- 26368665 TI - Comparing two tyrosine kinase inhibitors for treatment of advanced renal cell carcinoma in Medicare and commercially insured patients. AB - OBJECTIVE: The objective of this study was to compare treatment characteristics, survival and costs for sunitinib and pazopanib for advanced renal cell carcinoma (RCC) in a real-world setting. METHODS: Using claims data, this observational, retrospective cohort study selected individuals aged 19 to 89 years, with commercial or Medicare insurance, advanced RCC, and at least one pharmacy claim for sunitinib or pazopanib between 1 November 2009 and 31 December 2012. Treatment characteristics (treatment interruption, adherence, duration and discontinuation), survival, and costs were measured up to 12 months. Statistical models were adjusted for age, gender, geographic region, race, and RxRisk-V score. RESULTS: At baseline, pazopanib patients exhibited significantly worse health status indicators (RxRisk-V score, number of pharmacy claims, and pre index total healthcare costs) than sunitinib patients. There were no differences in treatment characteristics or survival. Index medication costs (mean difference $5580, p = 0.03, adj p = 0.05) and total healthcare costs (mean difference $12,192, p = 0.09, adj p = 0.07) trended higher with sunitinib. Patients non adherent with sunitinib incurred significantly higher total costs compared to patients non-adherent with pazopanib (mean difference $17,680, p = 0.04, adj p = 0.01). CONCLUSIONS: Mortality data and proxy variables for treatment effectiveness indicate comparable clinical value for both medications. Sunitinib treatment trended towards higher index medication and total healthcare costs despite higher pre-index total costs and worse health status indicators at baseline with pazopanib. Non-adherence with sunitinib was associated with significantly higher total healthcare costs, which may indicate differences in tolerability between the two agents and requires further investigation. PMID- 26368666 TI - Stabilization of Kv1.5 channel protein by the inotropic agent olprinone. AB - Olprinone is an inotropic agent that inhibits phosphodiesterase (PDE) III and causes vasodilation. Olprinone has been shown to be less proarrhythmic and possibly affect expression of functional Kv1.5 channels that confer the ultra rapid delayed-rectifier K+ channel current (IKur) responsible for action potential repolarization. To reveal involvement of Kv1.5 channels in the less arrhythmic effect of olprinone, we examined effects of the agent on the stability of Kv1.5 channel proteins expressed in COS7 cells. Olprinone at 30-1000 nM increased the protein level of Kv1.5 channels in a concentration-dependent manner. Chase experiments showed that olprinone delayed degradation of Kv1.5 channels. Olprinone increased the immunofluorescent signal of Kv1.5 channels in the endoplasmic reticulum (ER) and Golgi apparatus as well as on the cell surface. Kv1.5-mediated membrane currents, measured as 4-aminopyridine-sensitive currents, were increased by olprinone without changes in their activation kinetics. A protein transporter inhibitor, colchicine, abolished the olprinone induced increase of Kv.1.5-mediated currents. The action of olprinone was inhibited by 4-aminopyridine, and was not mimicked by the application of 8-Bromo cAMP. Taken together, we conclude that olprinone stabilizes Kv1.5 proteins at the ER through an action as a chemical chaperone, and thereby increases the density of Kv1.5 channels on the cell membrane. The enhancement of Kv1.5 currents could underlie less arrhythmogenicity of olprinone. PMID- 26368667 TI - Propofol protects against opioid-induced hyperresponsiveness of airway smooth muscle in a horse model of target-controlled infusion anaesthesia. AB - General anaesthesia in horses is associated with elevated mortality rate in subjects suffering of heaves. Target-controlled infusion (TCI) of sedative hypnotic medications and opioids represents a total intravenous anaesthesia (TIVA) method validated in veterinary medicine. Since there are no data concerning the impact of these classes of drugs in inducing bronchial hyperresponsiveness (BHR) in horses, the aim of this study was to investigate the effect propofol and remifentanil on the contractile response of equine airway smooth muscle. The influence of propofol and remifentanil on the contractile response of equine isolated bronchi to electrical field stimulation (EFS) was assessed. The role of capsaicin-sensitive sensory nerves, inducible nitric oxide synthase (iNOS) and neurokinin 2 (NK2) receptor was also assessed. The interaction analysis was performed by Bliss Independence theory. Experiments were repeated in desensitized and passively sensitized airways. Remifentanil induced BHR in both non-sensitized and passively sensitized bronchi, (+56.33+/-8.01% and +99.10+/-14.52%, respectively; P<0.01 vs. control) and propofol significantly prevented this effect (P>0.05 vs. remifentanil). The inactivation of capsaicin sensitive sensory nerves via desensitization and blocking NK2 receptor inhibited the BHR remifentanil-induced (P>0.05 vs. controls). The inhibition of iNOS reverted the protective effect of propofol on the BHR induced by remifentanil (non-sensitized: +47.11+/-7.70%; passively sensitized: +70.51+/-11.39%; P<0.05 vs. control). Propofol synergistically interacted (overall ~40%) in preventing the remifentanil-induced BHR. Remifentanil induces BHR via stimulating capsaicin sensitive sensory nerves that facilitate the cholinergic neurotransmission through the activation of NK2 receptor. The propofol/remifentanil combination may be safely administered in course of TCI-TIVA procedures also in heaves affected horses. PMID- 26368669 TI - Application of a dynamic in vitro model with real-time determination of acetylcholinesterase activity for the investigation of tabun analogues and oximes. AB - Tabun-inhibited acetylcholinesterase (AChE) is rather resistant towards reactivation by oximes in vitro while in vivo experiments showed some protection of animals poisoned by this chemical warfare nerve agent after treatment with an oxime and atropine. In addition, AChE inhibited by close tabun analogues, N,N diethyltabun and N,N-di-n-propyltabun was completely resistant towards reactivation by oximes. In order to get more insight into potential mechanisms of this oxime resistance experiments with these toxic agents and the oximes obidoxime, 2-PAM, MMB-4 and HI-6 were performed utilizing a dynamic model with real-time determination of AChE activity. This experimental setup allowed the investigation of reactivation with minimized side reactions. The determined reactivation constants with tabun-inhibited human AChE were in good agreement with previously reported constants determined with a static model. N,N-diethyl- and N,N-di-n-propyltabun-inhibited human AChE could not be reactivated by oximes which indicates that the inadequate oxime effect was not due to re-inhibition by phosphonyloximes. Additional experiments with tabun-inhibited human and Rhesus monkey AChE revealed that no reactivation occurred with HI-6. These data give further support to the assumption that an interaction of tabun with residues in the active site gorge of AChE prevents effective reactivation by oximes, a mechanism which may also be the reason for the total oxime resistance of N,N diethyl- and N,N-di-n-propyltabun-inhibited human AChE. PMID- 26368668 TI - Dynamics of an Active-Site Flap Contributes to Catalysis in a JAMM Family Metallo Deubiquitinase. AB - The endosome-associated deubiquitinase (DUB) AMSH is a member of the JAMM family of zinc-dependent metallo isopeptidases with high selectivity for Lys63-linked polyubiquitin chains, which play a key role in endosomal-lysosomal sorting of activated cell surface receptors. The catalytic domain of the enzyme features a flexible flap near the active site that opens and closes during its catalytic cycle. Structural analysis of its homologues, AMSH-LP (AMSH-like protein) and the fission yeast counterpart, Sst2, suggests that a conserved Phe residue in the flap may be critical for substrate binding and/or catalysis. To gain insight into the contribution of this flap in substrate recognition and catalysis, we generated mutants of Sst2 and characterized them using a combination of enzyme kinetics, X-ray crystallography, molecular dynamics simulations, and isothermal titration calorimetry (ITC). Our analysis shows that the Phe residue in the flap contributes key interactions during the rate-limiting step but not to substrate binding, since mutants of Phe403 exhibit a defect only in kcat but not in KM. Moreover, ITC studies show Phe403 mutants have similar KD for ubiquitin compared to the wild-type enzyme. The X-ray structures of both Phe403Ala and the Phe403Trp, in both the free and ubiquitin bound form, reveal no appreciable structural change that might impair substrate or alter product binding. We observed that the side chain of the Trp residue is oriented identically with respect to the isopeptide moiety of the substrate as the Phe residue in the wild type enzyme, so the loss of activity seen in this mutant cannot be explained by the absence of a group with the ability to provide van der Waals interactions that facilitate the hyrdolysis of the Lys63-linked diubiquitin. Molecular dynamics simulations indicate that the flap in the Trp mutant is quite flexible, allowing almost free rotation of the indole side chain. Therefore, it is possible that these different dynamic properties of the flap in the Trp mutant, compared to the wild-type enzyme, manifest as a defect in interactions that facilitate the rate-limiting step. Consistent with this notion, the Trp mutant was able to cleave Lys48-linked and Lys11-linked diubiquitin better than the wild-type enzyme, indicating altered mobility and hence reduced selectivity. PMID- 26368670 TI - The mining chemical Polydadmac is cytotoxic but does not interfere with Cu induced toxicity in Atlantic salmon hepatocytes. AB - To speed up sedimentation of suspended solids the mining industry often uses flocculent chemicals. In this work we evaluated the cytotoxic and mechanistic effects of Polydadmac, and its basic component Dadmac, on fish cells. Dose response effects, temperature-dependent effects and impact of Dadmac and Polydadmac on Cu toxicity were studied in Atlantic salmon hepatocytes. We used the xCELLigence system and the MTT test for cytotoxicity assessments, and real time RT-qPCR to evaluate molecular effects. The results showed a cytotoxic response for Polydadmac but not for Dadmac. Elevated levels of Cu were cytotoxic. Moderately cytotoxic concentrations of Cu (100-1000 MUM) induced significant responses on the transcription of a number of genes in the cells, i.e. cuznsod (sod1), cat, mnsod (sod2), nfe2l2, hmox1, mta, casp3b, casp6, bclx, cyp1a, ccs, atp7a, app, mmp13, esr1, ppara, fads2 and ptgs2. A factorial PLS regression model for mnsod transcription showed a synergistic effect between Dadmac and Cu exposure in the cells, indicating an interaction effect between Dadmac and Cu on mitochondrial ROS scavenging. No interaction effects were seen for Polydadmac on Cu toxicity. In conclusion, Polydadmac is cytotoxic at elevated concentrations but appears to have low ability to interfere with Cu toxicity in Atlantic salmon liver cells. PMID- 26368671 TI - Gallic acid induces mitotic catastrophe and inhibits centrosomal clustering in HeLa cells. AB - Cancer cells divide rapidly, providing medical targets for anticancer agents. The polyphenolic gallic acid (GA) is known to be toxic for certain cancer cells. However, the cellular mode of action has not been elucidated. Therefore, the current study addressed a potential effect of GA on the mitosis of cancer cells. GA inhibited viability of HeLa cells in a dose-dependent and time-dependent manner. We could show, using fluorescence-activated cell sorting (FACS), that this inhibition was accompanied by elevated frequency of cells arrested at the G2/M transition. This cell-cycle arrest was accompanied by mitotic catastrophe, and formation of cells with multiple nuclei. These aberrations were preceded by impaired centrosomal clustering. We arrive at a model of action, where GA inhibits the progression of the cell cycle at the G2/M phase by impairing centrosomal clustering which will stimulate mitotic catastrophe. Thus, GA has potential as compound against cervical cancer. PMID- 26368672 TI - Placental Growth Factor as a Novel Marker in Uremia-Related Cardiovascular Disease. PMID- 26368673 TI - Neonatal oesophageal and axilla temperatures in the neonatal intensive care unit care. AB - AIM: To compare oesophageal and axilla temperatures in routine neonatal intensive care unit (NICU) care. METHODS: Prospective observational study of NICU infants with indwelling oral/nasogastric tubes. Three simultaneous temperature measurements were taken: Physitemp axilla, digital Premie Faichney axilla in predictive mode and Physitemp oesophageal. Temperatures were measured on two separate days. RESULTS: Fifty infants were studied over a range of gestational ages (median 28.9 weeks, IQR 25.8-30.6 weeks) and birthweights (median 1140 g, IQR 742-1498 g). Mean Physitemp oesophageal temperatures were 0.3 +/- 0.1 degrees C (range 0.1-0.6 degrees C) higher than Physitemp axilla temperatures. After adjustment for weight, the Physitemp oesophageal-Physitemp axilla difference remained constant over the average oesophageal-axilla temperature range studied (p = 0.07). Physitemp oesophageal temperatures were not affected by weight (p = 0.2) or postmenstrual age (p = 0.51). Physitemp axilla temperatures decreased with increasing weight (p = 0.03) and postmenstrual age (p = 0.048). The Physitemp oesophageal-Physitemp axilla difference was greater for infants in cribs (mean +/- SD = 0.4 +/- 0.1 degrees C) than in incubators (mean +/- SD = 0.3 +/- 0.1 degrees C, p < 0.001). The relationship between oesophageal and digital Premie Faichney axilla temperature was similar to oesophageal and axilla Physitemp temperatures. CONCLUSION: Over a range of infant temperatures encountered in routine NICU care, oesophageal temperature is higher than axilla temperature, although the difference is small. Axillary temperatures measured by digital thermometers in predictive mode are comparable to core oesophageal temperatures. PMID- 26368674 TI - Intra-Arterial Chemotherapy for Retinoblastoma: A Single-Center Experience. AB - BACKGROUND: Studies conducted in recent years have reported promising results regarding the treatment of retinoblastoma with the intra-arterial use of melphalan. In the present study, we intended to report the results of intra arterial chemotherapy with melphalan (IACT) in the treatment of newly diagnosed or relapsed-refractory retinoblastoma patients at the Department of Pediatric Oncology of Hacettepe University, Ankara, Turkey. MATERIALS AND METHODS: This was a retrospective study of patients with intraocular retinoblastoma who were treated with IACT from December 2011 to May 2014. A total of 56 eyes of 46 consecutive patients (30 males and 16 females) were included in the study. Forty four eyes received systemic chemotherapy upon diagnosis (systemic chemotherapy group, SCG), and 12 eyes were those of newly diagnosed patients (primary intra arterial melphalan group, PIAG). The choice of the IACT dose was based on age. Tumor control and globe salvage with IACT were analyzed. Complete blood counts were examined 7 days after the IACT for systemic toxicity. Ocular toxicities such as proptosis, eyelid edema, ocular motility, and retinal and optic atrophy were assessed by an ocular oncologist with regular ophthalmologic examinations. RESULTS: Enucleation was avoided overall in 66% (37/56) of the eyes, including 75% (9/12) in the PIAG and 64% (28/44) in the SCG patients. The 1-year enucleation-free survival rate was 56.7% at a median follow-up time of 11.9 months (range 0.27-27.6). IACT was administered in a total of 124 cycles (ranging from 1 to 7 cycles, mean 2.3). The responses were as follows: regression of the retinal tumor in 27 eyes and improvements in vitreous seeding in 5 of 15 eyes. The further treatment requirements after IACT were as follows: enucleation in 19 eyes (10 with vitreous seeding), radiotherapy in 3 eyes, systemic chemotherapy in 1 eye, and local therapy in 1 eye. No severe systemic side effects occurred. Transient swelling of the eyelids (22 patients), conjunctival chemosis (12 patients), upper eyelid ptosis (5 patients), redness over the frontal area (3 patients), limitation of ocular motility (3 patients) and mild proptosis (1 patient) were detected. Retinal pigment epithelial alterations (30 patients) and optic atrophy (3 patients) were seen in the late follow-up. CONCLUSIONS: Globe salvage and avoidance of radiotherapy may be achieved by IACT with limited toxicity. This treatment is efficient, repeatable and safe. PMID- 26368676 TI - Estimation of Nickel in Different Smokeless Tobacco Products and Their Impact on Human Health of Oral Cancer Patients. AB - It has been extensively investigated that the chewing of smokeless tobacco (SLT) products may enhance the inflammation of the oral cavity. The aim of the present study is to evaluate the relationship between nickel (Ni) exposure via different SLT products with oral cancer (different sites) incidence in the population of Sindh, Pakistan. The different brands of SLT products (mainpuri, gutkha, and moist snuff) commonly consumed by the studied population were analyzed for Ni contents. The biological samples of oral cancer patients and noncancerous control subjects of both genders, who have or have not consumed SLT products, were collected. The concentration of Ni in biological samples and SLT products were measured by electrothermal atomic absorption spectrophotometer after microwave assisted acid digestion. The validity and accuracy of the methodology were checked by using certified reference materials. The results of this study showed that the Ni level was significantly higher in scalp hair and blood samples of oral cancer patients compared to controls (P < 0.01). The study suggested that exposure of Ni as a result of chewing different SLT products may be synergistic with risk factors associated with oral cancer. PMID- 26368675 TI - Prevalence of the dhfr and dhps Mutations among Pregnant Women in Rural Burkina Faso Five Years after the Introduction of Intermittent Preventive Treatment with Sulfadoxine-Pyrimethamine. AB - BACKGROUND: The emergence and spread of drug resistance represents one of the biggest challenges for malaria control in endemic regions. Sulfadoxine pyrimethamine (SP) is currently deployed as intermittent preventive treatment in pregnancy (IPTp) to prevent the adverse effects of malaria on the mother and her offspring. Nevertheless, its efficacy is threatened by SP resistance which can be estimated by the prevalence of dihydropteroate synthase (dhps) and dihydrofolate reductase (dhfr) mutations. This was measured among pregnant women in the health district of Nanoro, Burkina Faso. METHODS: From June to December 2010, two hundred and fifty six pregnant women in the second and third trimester, attending antenatal care with microscopically confirmed malaria infection were invited to participate, regardless of malaria symptoms. A blood sample was collected on filter paper and analyzed by PCR-RFLP for the alleles 51, 59, 108, 164 in the pfdhfr gene and 437, 540 in the pfdhps gene. RESULTS: The genes were successfully genotyped in all but one sample (99.6%; 255/256) for dhfr and in 90.2% (231/256) for dhps. The dhfr C59R and S108N mutations were the most common, with a prevalence of 61.2% (156/255) and 55.7% (142/255), respectively; 12.2% (31/255) samples had also the dhfr N51I mutation while the I164L mutation was absent. The dhps A437G mutation was found in 34.2% (79/231) isolates, but none of them carried the codon K540E. The prevalence of the dhfr double mutations NRNI and the triple mutations IRNI was 35.7% (91/255) and 11.4% (29/255), respectively. CONCLUSION: Though the mutations in the pfdhfr and pfdhps genes were relatively common, the prevalence of the triple pfdhfr mutation was very low, indicating that SP as IPTp is still efficacious in Burkina Faso. PMID- 26368677 TI - Plasmonic random nanostructures on fiber tip for trapping live cells and colloidal particles. AB - We demonstrate optical trapping on a gold-coated single-mode fiber tip as excited by 980-nm laser radiation. The trapping force here is not due to common plasmonic localization, but dominated by the combined effect of thermophoresis and thermal convection. The reported scheme only requires simple thin-film deposition. More importantly, efficient broadband plasmonic absorption of the gold random nanostructures, aided by purely Gaussian excitation profile from the fiber core, has led to very low trapping-power threshold typically in hundreds of microwatts. This highly versatile fiber-based trapping scheme clearly offers many potential application possibilities in life sciences as well as engineering disciplines. PMID- 26368678 TI - Integrated remotely tunable optical delay line for millimeter-wave beam steering fabricated in an InP generic foundry. AB - A compact and fabrication-tolerant integrated remotely tunable optical delay line is proposed for millimeter-wave beam steering and is fabricated in an InP generic foundry. The proposed delay line is based on a spectrally cyclic-arrayed waveguide grating feedback loop. Its major features include the tolerant architecture with reduced chip size, and bi-directional operation with simplified remote tuning. Moreover, its cyclic feature guarantees further cascaded operations either for 2D radio beam steering or for high-resolution delay generation. The experimental results show less than 6.5-dB insertion loss of the integrated delay line. Five different delays from 0 to 71.6 ps are generated with less than 0.67-ps delay errors. PMID- 26368679 TI - On-chip silicon waveguide Bragg grating photonic temperature sensor. AB - Resistance thermometry is a time-tested method for taking temperature measurements. In recent years, fundamental limits to resistance-based approaches have spurred considerable interest in developing photonic temperature sensors as a viable alternative. In this study, we demonstrate that our photonic thermometer, which consists of a silicon waveguide integrated with a Bragg grating, can be used to measure temperature changes over the range of 5 degrees C 160 degrees C, with a combined expanded uncertainty [k=2, 95% confidence level] of 1.25 degrees C. Computational modeling of the sensor predicts the resonance wavelength and effective refractive index within 4% of the measured value. PMID- 26368680 TI - Low-DMD few-mode fiber with distributed long-period grating. AB - We propose a distributed grating-assisted few-mode fiber (DG-FMF) to reduce the differential mode delay (DMD). By introducing asymmetric long-period fiber gratings with random exposure directions in a step-index few-mode fiber during fiber manufacture process, the strong random mode coupling is generated along the entire length of the fiber. Simulation results show that mean DMD in the DG-FMF can be reduced to less than 12 ns at a distance of 100 km with a period of 514 MUm and grating strength of 1*10(-6). The DMD reduction in our DG-FMF is guaranteed within the entire C-band, and in a wide temperature range from -20 degrees C to +60 degrees C. PMID- 26368681 TI - Polarization-independent nonuniform grating couplers on silicon-on-insulator. AB - Grating couplers are proposed for polarization-independent coupling of light between a single-mode fiber and a 220-nm-thick channel waveguide on silicon-on insulator. The grating couplers have nonuniform grating periods that are composed of the intersection or union of a set of two near-optimal TE- and TM-grating periods. The proposed grating couplers have a coupling efficiency greater than 20% and polarization dependent loss (PDL) lower than 0.5 dB within 3-dB bandwidth in design. For the evaluation of the design concept, a fabricated intersection grating coupler has the PDL of less than 0.8 dB within the wavelength range of 1540 to 1560 nm, and the coupling efficiency is ~18%. PMID- 26368682 TI - Performance of a dual Fabry-Perot cavity refractometer. AB - We have built and characterized a refractometer that utilizes two Fabry-Perot cavities formed on a dimensionally stable spacer. In the typical mode of operation, one cavity is held at vacuum, and the other cavity is filled with nitrogen gas. The differential change in length between the cavities is measured as the difference in frequency between two helium-neon lasers, one locked to the resonance of each cavity. This differential change in optical length is a measure of the gas refractivity. Using the known values for the molar refractivity and virial coefficients of nitrogen, and accounting for cavity length distortions, the device can be used as a high-resolution, multi-decade pressure sensor. We define a reference value for nitrogen refractivity as n-1=(26485.28+/-0.3)*10(-8) at p=100.0000 kPa, T=302.9190 K, and lambda(vac)=632.9908 nm. We compare pressure determinations via the refractometer and the reference value to a mercury manometer. PMID- 26368683 TI - Thin-film filter, wavelength-locked, multi-laser cavity for dense wavelength beam combining of broad-area laser diode bars. AB - We report on individual wavelength locking of a multiplet of 100-MUm broad-area laser diode emitters arranged on a 50% fill-factor bar by means of a single external multi-laser cavity using an ultra-narrowband thin-film filter as a dispersive optical element. The achieved wavelength-locked output power is 216 W, corresponding to an electrical-to-optical conversion efficiency of about 49.7%. The 45 emitters of the laser diode bar are stabilized within a spectral range of about 6.4 nm. Our approach is suited for killowatt-class dense wavelength beam combining of direct diode lasers. PMID- 26368684 TI - Single-shot speckle reduction in numerical reconstruction of digitally recorded holograms: comment. AB - We comment on a recent Letter by Hincapie et al. [Opt. Lett.40, 1623 (2015)], in which the authors proposed a method to reduce the speckle noise in digital holograms. This method was previously published by us in Maycock ["Improving reconstructions of digital holograms," Ph.D. thesis (National University of Ireland, 2012)] and Maycock and Hennelly [Improving Reconstructions of Digital Holograms: Speckle Reduction and Occlusions in Digital Holography (Lambert Academic, 2014)]. We also wish to highlight an important limitation of the method resulting from the superposition of different perspectives of the object/scene, which was not addressed in their Letter. PMID- 26368685 TI - Degree of polarization (uniformity) and depolarization index: unambiguous depolarization contrast for optical coherence tomography. AB - The degree of polarization (uniformity) has attracted increased interest as a functional contrast in optical coherence tomography (OCT). However, its computation from a single polarization state suggests an ambiguity that is strongly dependent on a sample's orientation. We here propose an improved metric to present depolarization with respect to the optical system rather than the propagating field. Using numerical simulations and optical frequency domain imaging, we evaluate the conventional DOP(U) for different polarization states and compare its performance with the unambiguous depolarization index. PMID- 26368686 TI - Control of lateral thickness gradients of Mo-Si multilayer on curved substrates using genetic algorithm. AB - An inversion method based on a genetic algorithm has been developed to control the lateral thickness gradients of a Mo-Si multilayer deposited on curved substrates by planar magnetron sputtering. At first, the sputtering distribution of the target is inversed from coating thickness profiles of flat substrates at different heights. Then, the speed profiles of substrates sweeping across the target are optimized according to the desired coating thickness profiles of the primary and secondary mirrors in a two-bounce projection system. The measured coating thickness profiles show that the non-compensable added figure error is below 0.1 nm rms, and the wavelength uniformity across each mirror surface is within +/-0.2% P-V. The inversion method introduced here exhibits its convenience in obtaining the sputtering distribution of the target and efficiency in coating iterations during process development. PMID- 26368687 TI - Enhancement of the sensitivity of a temperature sensor based on fiber Bragg gratings via weak value amplification. AB - We present a proof-of-concept experiment aimed at increasing the sensitivity of Fiber-Bragg-gratings temperature sensors by making use of a weak-value amplification scheme. The technique requires only linear optics elements for its implementation and appears as a promising method for increasing the sensitivity than state-of the-art sensors can currently provide. The device implemented here is able to generate a shift of the centroid of the spectrum of a pulse of ~0.035 nm/ degrees C, a nearly fourfold increase in sensitivity over the same fiber Bragg-grating system interrogated using standard methods. PMID- 26368688 TI - Air-structured optical fiber drawn from a 3D-printed preform. AB - A structured optical fiber is drawn from a 3D-printed structured preform. Preforms containing a single ring of holes around the core are fabricated using filament made from a modified butadiene polymer. More broadly, 3D printers capable of processing soft glasses, silica, and other materials are likely to come on line in the not-so-distant future. 3D printing of optical preforms signals a new milestone in optical fiber manufacture. PMID- 26368689 TI - Random bit generation at tunable rates using a chaotic semiconductor laser under distributed feedback. AB - A semiconductor laser with distributed feedback from a fiber Bragg grating (FBG) is investigated for random bit generation (RBG). The feedback perturbs the laser to emit chaotically with the intensity being sampled periodically. The samples are then converted into random bits by a simple postprocessing of self differencing and selecting bits. Unlike a conventional mirror that provides localized feedback, the FBG provides distributed feedback which effectively suppresses the information of the round-trip feedback delay time. Randomness is ensured even when the sampling period is commensurate with the feedback delay between the laser and the grating. Consequently, in RBG, the FBG feedback enables continuous tuning of the output bit rate, reduces the minimum sampling period, and increases the number of bits selected per sample. RBG is experimentally investigated at a sampling period continuously tunable from over 16 ns down to 50 ps, while the feedback delay is fixed at 7.7 ns. By selecting 5 least-significant bits per sample, output bit rates from 0.3 to 100 Gbps are achieved with randomness examined by the National Institute of Standards and Technology test suite. PMID- 26368690 TI - Terahertz radiation from high-order guided mode excited by a train of electron bunches. AB - A new radiation scheme, which adopts the high-order harmonics of a train of electron bunches to excite the high-order guided mode, is proposed and investigated by numerical simulations. By applying this scheme, the radiation with frequency close to 1 THz is generated from a waveguide with relatively big size structure, and the bunching frequency is much lower than the radiation frequency. This scheme may offer a promising candidate for practical terahertz source since it breaks the two main bottlenecks of the vacuum electronic devices in the terahertz region: very tiny-size structure and unapproachable electron beam. PMID- 26368691 TI - Facet-rotated echelle grating for cyclic wavelength router with uniform loss and flat passband. AB - A novel method for designing a cyclic echelle grating wavelength router with uniform loss and flat passband is proposed and experimentally demonstrated. A 4*4 cyclic wavelength router with a channel spacing of 400 GHz at 1550 nm wavelength band is designed and fabricated in InP. Measurement results show that the loss of 16 input-output combinations varies from 9 to 19.3 dB in a conventional design, with a nonuniformity of 10.3 dB, while the 1-dB spectral bandwidth is only 0.3 nm. By rotating angles of grating facets according to an appropriately designed distribution function, the loss nonuniformity is reduced to 1.5 dB, and a flat top spectral response with 1 dB bandwidth of 1.0 nm is achieved simultaneously. PMID- 26368692 TI - Rapid measurement of individual cone photoreceptor pointing using focus diversity. AB - A novel method is presented to rapidly measure the pointing direction of individual human cone photoreceptors using adaptive-optics (AO) retinal imaging. For a fixed entrance pupil position, the focal plane is rapidly modulated to image the guided light in various axial planes. For cones with different pointing directions, this focus diversity will cause a shift in their apparent position, allowing for their relative pointing to be determined. For four normal human subjects, retinal images were acquired, registered, and the positions of individual cones tracked throughout the dataset. Variation in cone tilt was 0.02 radians, agreeing with other objective measurements on the same subjects at the same retinal locations. PMID- 26368693 TI - Gold triple-helix mid-infrared metamaterial by STED-inspired laser lithography. AB - In analogy to wire-grid polarizers for linear polarization, metal-helix metamaterials can act as broadband circular polarizers. This concept has brought circular-polarization capabilities to mid-infrared and terahertz frequencies, which were previously difficult to access. Due to the lack of rotational symmetry, however, single-helix metamaterials exhibit unwanted circular polarization conversions. Recent theoretical work showed that conversions can be fully eliminated by intertwining N=3 or 4 helices within each unit cell. While direct laser writing in positive-tone photo-resist yielded good results for single-helix metamaterials operating at mid-infrared frequencies, the axial resolution is insufficient for N-helix metamaterials. Here, we use stimulated emission depletion-inspired three-dimensional laser lithography to fabricate such microstructures. We measure all entries of the Jones transmission and reflection matrices and show experimentally that polarization conversions are minimized, in good agreement with theory. PMID- 26368694 TI - Composite modified Luneburg model of human eye lens. AB - A new lens model based on the gradient-index Luneburg lens and composed of two oblate half spheroids of different curvatures is presented. The spherically symmetric Luneburg lens is modified to create continuous isoindicial contours and to incorporate curvatures that are similar to those found in a human lens. The imaging capabilities of the model and the changes in the gradient index profile are tested for five object distances, for a fixed geometry and for a fixed image distance. The central refractive index decreases with decreasing object distance. This indicates that in order to focus at the same image distance as is required in the eye, a decrease in refractive power is needed for rays from closer objects that meet the lens surface at steeper angles compared to rays from more distant objects. This ensures a highly focused image with no spherical aberration. PMID- 26368695 TI - Graphene-coated tilted fiber-Bragg grating for enhanced sensing in low-refractive index region. AB - We propose and experimentally demonstrate a method to significantly extend the sensitive window of tilted fiber-Bragg grating (TFBG) into low-refractive-index region with the integration of graphene coating. The coupling between cladding modes of TFBG and graphene coating results in an obvious modification of the cladding-mode envelope, which provides a sensitive regime relying on graphene's complex refractive index. Interacting the graphene-coated TFBG with various aqueous solutions, we observe strongly enhanced sensitivity in the low-refractive index region of 1-1.428, which is about 10-fold extended from that of the unloaded TFBG. The graphene-coated TFBGs present great potentials in the biochemical sensing window. PMID- 26368696 TI - Surface plasmon excitation at near-infrared wavelengths in polymer optical fibers. AB - We report the first excitation of surface plasmon waves at near-infrared telecommunication wavelengths using polymer optical fibers (POFs) made of poly(methyl methacrylate) (PMMA). For this, weakly tilted fiber-Bragg gratings (TFBGs) have been photo-inscribed in the core of step-index POFs and the fiber coated with a thin gold layer. Surface plasmon resonance is excited with radially polarized modes and is spectrally observed as a singular extinction of some cladding-mode resonances in the transmitted amplitude spectrum of gold-coated TFBGs. The refractometric sensitivity can reach ~550 nm/RIU (refractive index unit) with a figure of merit of more than 2000 and intrinsic temperature self compensation. This kind of sensor is particularly relevant to in situ operation. PMID- 26368697 TI - Nonlinear Raman-Nath diffraction of femtosecond laser pulses in a 2D nonlinear photonic crystal. AB - We study second-harmonic generation (SHG) of femtosecond laser pulses in a rectangular two-dimensional nonlinear photonic crystal (NLPC). Multiple SH beams were observed in the vicinity of the propagation direction of the fundamental beam. It has been verified that the angular positions of these beams obey the conditions of nonlinear Raman-Nath diffraction (NRND). The measured SH spectra of specific NRND orders consist of narrow peaks that experience a high-frequency spectral shift as the order grows. We derive an analytical expression for the process studied and find the theoretical results to be in good agreement with the experimental data. We estimate the enhancement factor of nonlinear Raman-Nath diffraction in 2D NLPC to be 70. PMID- 26368698 TI - Triply resonant coherent four-wave mixing in silicon nitride microresonators. AB - Generation of multiple tones using four-wave mixing (FWM) has been exploited for many applications, ranging from wavelength conversion to frequency comb generation. FWM is a coherent process, meaning that its dynamics strongly depend on the relative phase among the waves involved. The coherent nature of FWM has been exploited for phase-sensitive processing in different waveguide structures, but it has never been studied in integrated microresonators. Waveguides arranged in a resonant way allow for an effective increase in the wavelength conversion efficiency (at the expense of a reduction in the operational bandwidth). In this Letter, we show that phase shaping of a three-wave pump provides an extra degree of freedom for controlling the FWM dynamics in microresonators. We present experimental results in single-mode, normal-dispersion high-Q silicon nitride resonators, and numerical calculations of systems operating in the anomalous dispersion regime. Our results indicate that the wavelength conversion efficiency and modulation instability gain in microcavities pumped by multiple waves can be significantly modified with the aid of simple lossless coherent control techniques. PMID- 26368699 TI - Flexible generation/conversion/exchange of fiber-guided orbital angular momentum modes using helical gratings. AB - By exploiting helical gratings (HGs), we propose and simulate flexible generation, conversion, and exchange of fiber-guided orbital angular momentum (OAM) modes. HGs can enable the generation of OAM modes, and the OAM conversion between two arbitrary modes guided in fibers. A specific HG can exchange the OAM states of a couple of OAM modes, i.e., OAM exchange. In addition, a Fabry-Perot (F-P) cavity cascaded with two identical reflective HGs can reflect converted OAM modes with a comb spectrum. The HG-based generation/conversion/exchange of OAM modes are dependent on helix period, orientation, and the fold number of helical fringes. The proposed method of generation, conversion, and exchange of fiber guided OAM modes using HGs is flexible and well compatible with OAM fibers, featuring a high conversion efficiency close to 100% and a conversion bandwidth about 10 nm in transmission spectra, while less than 1 nm in reflection spectra. PMID- 26368700 TI - Two-grating Talbot bands spectral-domain interferometer. AB - A configuration for Talbot bands is presented in which two tilted gratings replace the splitter normally used for recombining the signals from the two interferometer arms. The two optical beams from the interferometer are launched by two fiber leads tightly brought together in the front focal plane of a collimating lens. As the tips of the two fibers are slightly off-axis, the emergent beams after the collimating lens are not parallel. In combination with the two tilted gratings, the nonparallel launching of the two beams leads to a total elimination of mirror terms even when the two beams overlap on either grating. The effects of several geometrical parameters on the visibility performance versus optical path difference between the two arm lengths of the interferometer are evaluated. PMID- 26368701 TI - Femtosecond laser pulse shaping at megahertz rate via a digital micromirror device. AB - In this Letter, we present a scanner and digital micromirror device (DMD)-based ultrafast pulse shaper, i.e., S-DUPS, for programmable ultrafast pulse modulation, achieving a shaping rate of 2 MHz. To our knowledge, the S-DUPS is the fastest programmable pulse shaper reported to date. In the S-DUPS, the frequency spectrum of the input pulsed laser is first spread horizontally, and then mapped to a thin stripe on the DMD programmed with phase modulation patterns. A galvanometric scanner, synchronized with the DMD, subsequently scans the spectrum vertically on the DMD to achieve a shaping rate up to 10 s MHz. A grating pair and a cylindrical lens in front of the DMD compensate for the temporal and spatial dispersion of the system. To verify the concept, experiments were conducted with the DMD and the galvanometric scanner operated at 2 kHz and 1 kHz, respectively, achieving a 2 MHz speed for continuous group velocity dispersion tuning, as well as 2% efficiency. Up to 5% efficiency of S-DUPS can be expected with high efficiency gratings and optical components of proper coatings. PMID- 26368702 TI - Mode selection in InAs quantum dot microdisk lasers using focused ion beam technique. AB - Optically pumped InAs quantum dot microdisk lasers with grooves etched on their surface by a focused ion beam are studied. It is shown that the radial grooves, depending on their length, suppress the lasing of specific radial modes of the microdisk. Total suppression of all radial modes, except for the fundamental radial one, is also demonstrated. The comparison of laser spectra measured at 78 K before and after ion beam etching for a microdisk of 8 MUm in diameter shows a sixfold increase of mode spacing, from 2.5 to 15.5 nm, without a significant decrease of the dominant mode quality factor. Numerical simulations are in good agreement with experimental results. PMID- 26368703 TI - Rotation of large asymmetrical absorbing objects by Laguerre-Gauss beams. AB - In this Letter, we show the manipulation and rotation of opaque graphite through adhesion with optically trapped polystyrene spheres. The absorbing graphite is rotated by the orbital angular momentum transfer from a Laguerre-Gauss laser mode and is trapped due to the presence of refracting spheres. This technique is effective for trapping and rotating absorbing objects of all sizes, including those larger than the laser mode. PMID- 26368704 TI - Frequency analysis for an extended photoacoustic transport model. AB - In photoacoustic imaging, the signal attenuation is a well-known source of artifacts over the image reconstruction. It is recognized that this is caused by optical absorption effects and by the ultrasound broadband scattering. However, the sound dispersion is generally neglected, although it appears notably in thick or heterogeneous tissues. In the present Letter, we give an experimental example in which both attenuation and sound dispersion are dealt with as relevant features to be taken into consideration. An analytic perspective of these perturbations leads us to a waveform transport-model extension that provides a linear description of the induced acoustic effects. We find a near match between the theoretical predictions and the experimental results in the frequency domain. These outcomes approximate projection data that represent forward solutions in photoacoustic image reconstruction. PMID- 26368705 TI - Low-peak-to-average power ratio and low-complexity asymmetrically clipped optical orthogonal frequency-division multiplexing uplink transmission scheme for long reach passive optical network. AB - In this Letter, we propose a discrete Hartley transform (DHT)-spread asymmetrically clipped optical orthogonal frequency-division multiplexing (DHT-S ACO-OFDM) uplink transmission scheme in which the multiplexing/demultiplexing process also uses the DHT algorithm. By designing a simple encoding structure, the computational complexity of the transmitter can be reduced from O(Nlog(2)(N)) to O(N). At the probability of 10(-3), the peak-to-average power ratio (PAPR) of 2-ary pulse amplitude modulation (2-PAM)-modulated DHT-S-ACO-OFDM is approximately 9.7 dB lower than that of 2-PAM-modulated conventional ACO-OFDM. To verify the feasibility of the proposed scheme, a 4-Gbit/s DHT-S-ACO-OFDM uplink transmission scheme with a 1?64 way split has been experimentally implemented using 100-km standard single-mode fiber (SSMF) for a long-reach passive optical network (LR-PON). PMID- 26368706 TI - Direct reconstruction method for time-domain fluorescence molecular lifetime tomography. AB - For the reconstruction of time-domain fluorescence molecular lifetime tomography, conventional methods based on the Laplace or Fourier transform utilize only part of the information from the measurement data, and rely on the selection of transformation factors. To make the best of all the measurement data, a direct reconstruction algorithm is proposed. The fluorescence yield map is first reconstructed with a full-time gate, and then an objective function for the inverse lifetime tomography (instead of the lifetime) is developed so as to avoid dealing with the singularity of the zero points in the lifetime image. Through simulations and physical phantom experiments, the proposed algorithm is demonstrated to have high localization accuracy for fluorescent targets, high quantification accuracy for fluorescence lifetime, and good contrast between different fluorescence targets. PMID- 26368707 TI - Evanescent wave optical binding forces on spherical microparticles. AB - In this Letter, we demonstrate stable optical binding of spherical microparticles in counter-propagating evanescent optical fields formed by total reflection at a dielectric interface. The microspheres are observed to form one-dimensional chains oriented parallel to the direction of propagation of the beams. We characterize the strength of the optical binding interaction by measuring the extent of Brownian position fluctuations of the optically bound microspheres and relating this to a binding spring constant acting between adjacent particles. A stronger binding interaction is observed for particles near the middle of the chain, and the dependence of the binding strength on incident laser power and number of particles in the chain is determined. PMID- 26368708 TI - Enhancing the sensitivity of poly(methyl methacrylate) based optical fiber Bragg grating temperature sensors. AB - In poly(methyl methacrylate) (PMMA)-based optical fiber gratings (POFBGs), the temperature response is determined by thermal expansion and the thermo-optic effect of the fiber. Because thermal expansion introduces a positive change and the thermo-optic effect introduces a negative change in the Bragg wavelength of the POFBG, they cancel out each other to some extent, leading to reduced and varying temperature sensitivity. By pre-straining a POFBG, the contribution of thermal expansion can be removed, and, consequently, the temperature sensitivity of POFBG can be greatly enhanced. Theoretical analysis also indicates a reduced thermo-optic coefficient of POFBG due to restrained linear expansion that matches experimental results. PMID- 26368709 TI - High-level integration of three-dimensional microcoils array in fused silica. AB - Rapid and facile creation of three-dimensional (3D) microcoils array in a "lab-on a-chip" platform is a big challenge in micromachining. Here we report a method based on an improved femtosecond-laser wet-etch (FLWE) technology and metal microsolidifying process for the fabrication of 3D microcoils array inside fused silica. Based on this approach, we fabricated microcoil arrays such as 3*3 O shaped microcoils array and 4*4 liner microcoils array. By injecting high-melting point alloy, the electrocircuit of microcoils array can hardly be disconnected. The microcoils array also exhibits good uniformity and a high integration level. It shows promise as a real application device. PMID- 26368710 TI - Spectral-temporal compressive imaging. AB - This Letter presents a compressive camera that integrates mechanical translation and spectral dispersion to compress a multi-spectral, high-speed scene onto a monochrome, video-rate detector. Experimental reconstructions of 17 spectral channels and 11 temporal channels from a single measurement are reported for a megapixel-scale monochrome camera. PMID- 26368711 TI - Strong Raman-induced noninstantaneous soliton interactions in gas-filled photonic crystal fibers. AB - We have developed an analytical model based on the perturbation theory to study the optical propagation of two successive solitons in hollow-core photonic crystal fibers filled with Raman-active gases. Based on the time delay between the two solitons, we have found that the trailing soliton dynamics can experience unusual nonlinear phenomena, such as spectral and temporal soliton oscillations and transport toward the leading soliton. The overall dynamics can lead to a spatiotemporal modulation of the refractive index with a uniform temporal period and a uniform or chirped spatial period. PMID- 26368712 TI - Dynamics of laser-induced radial birefringence in silver-doped glasses. AB - Silver ion-exchanged glass exhibits nonlinear optical properties upon interacting with intense light beams. The thermal effect due to the nanoparticles' light absorption induces radial stress, and consequently, a radial birefringence on the glass surface. The induced birefringence possesses a topological charge of 1 in the transverse plane of the glass, i.e., cylindrical symmetry. Therefore, when the glass is illuminated with a circularly polarized light beam, a portion of the incoming beam flips its polarization handedness, since the plate is birefringent, and gains an orbital angular momentum of +/-2 in units of the Planck constant. This is referred to as optical spin-to-orbital angular momentum conversion, and can be understood by means of the Pancharatnam-Berry phase. Here, we design a pump-probe setup to study and observe the dynamics of optical angular momentum coupling in real time. We show that this effect can be permanent or reversible, depending on the power and interaction time of the pump beam. In particular, an intrinsic power-dependent birefringence hysteresis is observed on the sample after interaction with and the relaxation of the irradiated point. PMID- 26368713 TI - Broadband interferometric characterization of divergence and spatial chirp. AB - We demonstrate a spectral interferometric method to characterize lateral and angular spatial chirp to optimize intensity localization in spatio-temporally focused ultrafast beams. Interference between two spatially sheared beams in an interferometer will lead to straight fringes if the wavefronts are curved. To produce reference fringes, we delay one arm relative to another in order to measure fringe rotation in the spatially resolved spectral interferogram. With Fourier analysis, we can obtain frequency-resolved divergence. In another arrangement, we spatially flip one beam relative to the other, which allows the frequency-dependent beamlet direction (angular spatial chirp) to be measured. Blocking one beam shows the spatial variation of the beamlet position with frequency (i.e., the lateral spatial chirp). PMID- 26368714 TI - Creating order with the help of randomness: generating transversely random, longitudinally invariant vector optical fields. AB - We show that it is possible to generate transversely random, diffraction free/longitudinally invariant vector optical fields. The randomness in transverse polarization distribution complements a previously studied one in intensity of scalar Bessel-type beams, adding another degree of freedom to control these beams. Moreover, we show that the relative transversely random phase distribution is also conserved along the optical axis. Thus, intensity, phase, and polarization of Bessel-type beams can be transversely random/arbitrary while invariant upon propagation. Such fields may find applications in encryption/secure communications, optical trapping, etc. PMID- 26368715 TI - Linearly polarized random fiber laser with ultimate efficiency. AB - Linearly polarized pumping of a random fiber laser made of a 500-m PM fiber with PM fiber-loop mirror at one fiber end results in generation of linearly polarized radiation at 1.11 MUm with the polarization extinction ratio as high as 25 dB at the output power of up to 9.4 W. The absolute optical efficiency of pump-to Stokes wave conversion reaches 87%, which is close to the quantum limit and sets a record for Raman fiber lasers with random distributed feedback and with a linear cavity as well. Herewith, the output linewidth at high powers tends to saturation at a level of 1.8 nm. PMID- 26368716 TI - Modulated coupled nanowires for ultrashort pulses. AB - We predict analytically and confirm with numerical simulations that intermode dispersion in nanowire waveguide arrays can be tailored through periodic waveguide bending, facilitating flexible spatiotemporal reshaping without breakup of femtosecond pulses. This approach allows simultaneous and independent control of temporal dispersion and spatial diffraction that are often strongly connected in nanophotonic structures. PMID- 26368717 TI - Pressure measurements using hybrid femtosecond/picosecond rotational coherent anti-Stokes Raman scattering. AB - We investigate the feasibility of gas-phase pressure measurements using fs/ps rotational CARS. Femtosecond pump and Stokes pulses impulsively prepare a rotational Raman coherence, which is probed by a high-energy 5-ps pulse introduced at a time delay from the Raman preparation. These ultrafast laser pulses are shorter than collisional-dephasing time scales, enabling a new hybrid time- and frequency-domain detection scheme for pressure. Single-laser-shot rotational CARS spectra were recorded from N2 contained in a room-temperature gas cell for pressures from 0.4 to 3 atm and probe delays ranging from 16 to 298 ps. Sensitivity of the accuracy and precision of the pressure data to probe delay was investigated. The technique exhibits superior precision and comparable accuracy to previous laser-diagnostic pressure measurements. PMID- 26368719 TI - 110 nm versatile fiber optical parametric amplifier at 1.0 MUm. AB - The fiber optical parametric amplifier (FOPA) has been well investigated and widely adopted at the telecommunication window, and outstanding progress has been achieved in areas such as high gain, wide bandwidths, and even flexible gain spectrum shape. In contrast, a FOPA at the bio-favorable window, 1.0 MUm, has been largely underexploited, especially for its relatively limited bandwidth. Here, we demonstrate an all-fiber single-pump FOPA at 1.0 MUm with versatile performances, including ultrahigh gain (~52 dB), wide bandwidth (~110 nm), and good gain-spectrum flatness (~3 dB). To showcase the practical applications, the FOPA is utilized to amplify the broadband optical image signal from a spectrally encoded microscopy, yielding a sensitivity enhancement of 47 dB. Thus, it is promising that this all-fiber versatile FOPA works well as an add-on module in boosting sensitivity for existing optical systems at a 1.0 MUm window. PMID- 26368718 TI - Calibration-free 2f WMS with in situ real-time laser characterization and 2f RAM nulling. AB - This Letter demonstrates a new calibration-free 2f wavelength modulation spectroscopy (WMS) technique to measure gas concentration and pressure without the need for laser precharacterization. A 1650-nm laser diode is used for methane concentration and pressure measurements for pressures up to 4 bar and for a modulation index (m) of 2.2. All laser parameters such as the intensity, linear and nonlinear intensity modulation (IM), frequency modulation (FM) characteristics, the phase difference psi1 between the FM and the linear IM, and the phase difference psi2 between the FM and the nonlinear IM are accurately estimated in situ and in real time. This technique accounts for variations in these parameters that arise due to scanning of the laser's center wavelength, laser temperature variations, and aging of the laser. The laser is modulated at its phase quadrature frequency at which the linear IM and the FM are orthogonal to each other (psi1=90 degrees ). This ensures that the two linear IM-dependent distorting Fourier components are orthogonal to the detection axis, and the undistorted 2f signal is recovered. This simplifies the simulation and gas parameter-extraction process. Finally, 2f RAM nulling is implemented to remove the significant absorption-independent 2f residual amplitude-modulation (RAM) signal that is seen to cause significant distortion of the 2f signal and detector saturation. PMID- 26368720 TI - Widely tunable mid-infrared fiber laser source based on soliton self-frequency shift in microstructured tellurite fiber. AB - A turnkey fiber laser source generating high-quality pulses with a spectral sech shape and Fourier transform-limited duration of order 100 fs widely tunable in the 1.6-2.65 MUm range is presented. It is based on Raman soliton self-frequency shifting in the suspended-core microstructured TeO2-WO3-La2O3 glass fiber pumped by a hybrid Er/Tm fiber system. Detailed experimental and theoretical studies, which are in a very good agreement, of nonlinear pulse dynamics in the tellurite fiber with carefully measured and calculated parameters are reported. A quantitatively verified numerical model is used to show Raman soliton shift in the range well beyond 3 MUm for increased pump energy. PMID- 26368721 TI - Extended tunability of Nd-doped fiber lasers operating at 872-936 nm. AB - Efficient operation of an Nd-doped fiber laser operating in a wavelength-tunable configuration using a volume Bragg grating (VBG) is reported in this Letter. A high-power operation on the 4F3/2-4I9/2 transition of Nd3+ at short wavelengths below 900 nm is demonstrated for the first time in silica fibers. A high efficiency (47% laser conversion) output power up to 22 W and a narrow linewidth of 0.035 nm are achieved. This configuration is compared with a more conventional fiber laser setup using a bandpass filter and a highly reflective dichroic mirror. PMID- 26368722 TI - Few-cycle near-infrared pulses from a degenerate 1 GHz optical parametric oscillator. AB - We report the generation of transform-limited 4.3-cycle (23 fs) pulses at 1.6 MUm from a degenerate doubly resonant optical parametric oscillator (OPO) pumped by a 1 GHz mode-locked Ti:sapphire laser. A chi(2) nonlinear envelope equation was used to inform the experimental implementation of intracavity group-delay dispersion compensation, resulting in resonant pulses with a 169 nm full width half-maximum spectral bandwidth, close to the bandwidth predicted by theory. PMID- 26368723 TI - On-chip integrated differential optical microring refractive index sensing platform based on a laminar flow scheme. AB - We propose an on-chip integrated differential optical microring refractive index sensing platform which leverages laminar flow conditions. Close spacing between a sensing and a reference resonator, and sharing the same microfluidic channel allows the two resonators to experience similar environmental disturbances, such as temperature fluctuations and fluidic-induced transients, achieving reliable and sensitive sensing performance. We obtain a noise floor of 80.0 MHz (0.3 pm) and a bulk refractive index sensitivity of 17.0 THz per refractive index unit (RIU) (64.2 nm/RIU), achieving a limit of detection of 1.4*10(-5) RIU in a 30 min and an 8 degrees C window. PMID- 26368724 TI - Graphene mode-locked Cr:LiSAF laser at 850 nm. AB - We report, for the first time to our knowledge, a mode-locked femtosecond Cr:LiSAF laser initiated with a high-quality monolayer graphene saturable absorber (GSA), synthesized by chemical-vapor deposition. The tight-focusing resonator architecture made it possible to operate the Cr:LiSAF laser with only two 135 mW, 660 nm low-cost single-mode diode lasers. At a pump power of 270 mW, the laser produced nearly transform-limited 68 fs pulses with an average power of 11.5 mW at 850 nm. The repetition rate was around 132 MHz, corresponding to a pulse energy and peak power of 86 pJ and 1.26 kW, respectively. Once mode locking was initiated with the GSA, stable, uninterrupted femtosecond pulse generation could be sustained for hours. The saturation fluence and the modulation depth of the GSA were further determined to be 28 MUJ/cm2 and 0.62%, respectively. PMID- 26368726 TI - Broadband telecom to mid-infrared supercontinuum generation in a dispersion engineered silicon germanium waveguide. AB - We demonstrate broadband supercontinuum generation (SCG) in a dispersion engineered silicon-germanium waveguide. The 3 cm long waveguide is pumped by femtosecond pulses at 2.4 MUm, and the generated supercontinuum extends from 1.45 to 2.79 MUm (at the -30 dB point). The broadening is mainly driven by the generation of a dispersive wave in the 1.5-1.8 MUm region and soliton fission. The SCG was modeled numerically, and excellent agreement with the experimental results was obtained. PMID- 26368725 TI - Use of dyes to increase phase contrast for biological holographic microscopy. AB - Holographic microscopy is an emerging biological technique that provides amplitude and quantitative phase imaging, though the contrast provided by many cell types and organelles is low, and until now no dyes were known that increased contrast. Here we show that the metallocorrole Ga(tpfc)(SO3)2, which has a strong Soret band absorption, increases contrast in both amplitude and phase and facilitates tracking of Escherichia coli with minimal toxicity. The change in phase contrast may be calculated from the dye-absorbance spectrum using the Kramers-Kronig relations, and represents a general principle that may be applied to any dye or cell type. This enables the use of holographic microscopy for all applications in which specific labeling is desired. PMID- 26368727 TI - Diameter measurement of optical nanofibers using a composite photonic crystal cavity. AB - We demonstrate a method for making precise measurements of the diameter of a tapered optical fiber with a sub-wavelength diameter waist (an optical nanofiber). The essence of the method is to create a composite photonic crystal cavity by mounting a defect-mode grating on an optical nanofiber. The resultant cavity has a resonance wavelength that is sensitive to the nanofiber's diameter, allowing the diameter to be inferred from optical measurements. This method offers a precise, nondestructive, and in situ way to characterize the nanofiber diameter. PMID- 26368728 TI - Dark solitons in dual-core waveguides with dispersive coupling. AB - We report on new types of two-component one-dimensional dark solitons (DSs) in a dual-core waveguide model with normal group-velocity dispersion and Kerr nonlinearity in both cores, the coupling between which is also dispersive. In the presence of the dispersive coupling, quiescent DSs supported by the zero frequency background are always gray, being stable with the out-of-phase background, i.e., for opposite signs of the fields in the cores. In contrast, the background with a nonzero frequency supports quiescent black solitons which may be stable for both out-of-phase and in-phase backgrounds, if the dispersive coupling is sufficiently strong. Only DSs supported by the out-of-phase background admit an extension to the case of nonzero phase mismatch between the cores. PMID- 26368729 TI - A simple approach for estimating the refractive index structure parameter (Cn2) profile in the atmosphere. AB - Utilizing the so-called Thorpe scale as a measure of the turbulence outer scale, we propose a physically-based approach for the estimation of Cn2 profiles in the lower atmosphere. This approach only requires coarse-resolution temperature profiles (a.k.a., soundings) as input, yet it has the intrinsic ability to capture layers of high optical turbulence. The prowess of this computationally inexpensive approach is demonstrated by validations against observational data from a field campaign over Mauna Kea, Hawaii. PMID- 26368730 TI - Dual-color control and inhibition of direct laser writing in silver-containing phosphate glasses. AB - We report on dual-color control of femtosecond direct laser writing (DLW) in a noncommercial silver-containing zinc phosphate glass, thanks to an additional illumination with a cw (continuous wave) UV laser, either after the femtosecond irradiation or simultaneously. By tuning the cw UV power, we demonstrate the tunable control and inhibition of the production efficiency of laser-induced fluorescent silver clusters, leading up to 100% inhibition for simultaneous co illumination when the laser writing is performed close enough to the permanent structuring threshold. The role of the cw UV illumination is discussed in terms of inhibition of the silver cluster precursors or of dissolution of the laser induced silver clusters. These results show the ability of laser writing inhibition in our photosensitive silver-containing phosphate glass, which is a necessary step to further develop super-resolution laser writing approaches, such as STED-like DLW, either of fluorescent silver clusters or of silver metallic nanoparticles with plasmonic properties. PMID- 26368731 TI - Optical nonlinearities in high-confinement silicon carbide waveguides. AB - We demonstrate strong nonlinearities of n2=8.6+/-1.1*10(-15) cm2 W(-1) in single crystal silicon carbide (SiC) at a wavelength of 2360 nm. We use a high confinement SiC waveguide fabricated based on a high-temperature smart-cut process. PMID- 26368732 TI - Inline digital holographic movie based on a double-sideband filter. AB - This Letter proposes a new optical architecture based on a double-sideband filter, simultaneously applied at the Fourier plane, for inline digital holography. The proposed architecture not only allows removal of the conjugate images in the reconstruction process but also reduces the distortions that usually appear when using a single-sideband filter. We first introduce the mathematical model that explains the method and then describe the optical setup used for the implementation. The optical system includes a parallel aligned liquid crystal display placed at the Fourier plane that simultaneously filters positive and negative frequencies, when properly combined with linear polarizers. This feature makes the device useful to register dynamic processes. Finally, we tested the setup by registering a holographic movie of microscopic moving objects placed at different planes. PMID- 26368733 TI - Defocus noise suppression with combined frame difference and connected component methods in optical scanning holography. AB - Random phase masks can transform the defocus noise into a speckle-like pattern in optical scanning holography (OSH). In this Letter, we presented a speckle reduction based on combined frame difference and connected component method in a random phase-coded OSH system. The image quality of the reconstructed sections is improved with better visibility. PMID- 26368734 TI - High power, compact, picosecond MOPA based on single trench fiber with single polarized diffraction-limited output. AB - We experimentally demonstrate an all-solid Yb-doped 30 MUm core diameter single trench fiber. Measurements ensure a robust effective single-mode operation without the need of tight coiling as required for conventional fibers thanks to the ultralow NA (~0.038) and resonant ring surrounding the core. All-solid and cylindrical design ensures the suitability for mass scale production with the added benefit of all-fiberized device structure. A compact master oscillator power amplifier (MOPA) has been built using this fiber delivering ~23.5 ps pulses at 13.5 MHz repetition rate delivering up to ~52 W of average output power corresponding to a pulse energy of ~3.8 MUJ and peak power of >160 kW, while maintaining ~76% slope efficiency. The output beam exhibits a polarization extinction ratio of more than 15 dB and a M2 less than 1.15. PMID- 26368735 TI - Tunable narrowband microwave photonic filter created by stimulated Brillouin scattering from a silicon nanowire. AB - We demonstrate the first, to the best of our knowledge, functional signal processing device based on stimulated Brillouin scattering in a silicon nanowire. We use only 1 dB of on-chip stimulated Brillouin scattering gain to create an RF photonic notch filter with 48 dB of suppression, 98 MHz linewidth, and 6 GHz frequency tuning. This device has potential applications in on-chip microwave signal processing and establishes the foundation for the first CMOS-compatible high-performance RF photonic filter. PMID- 26368736 TI - Ultra-broad gain quantum cascade lasers tunable from 6.5 to 10.4 MUm. AB - We present a quantum cascade laser structure with an ultra-broad gain profile that covers the wavelength range from 6.5 to 10.4 MUm. In a grating-tuned external cavity, we demonstrated continuous tuning from 1027 cm(-1) to 1492 cm( 1) with this broad gain laser chip. We also fabricated distributed feedback quantum cascade laser arrays with this active region design and varied grating periods. We demonstrated single wavelength lasing from 962 (10.4) to 1542 cm(-1) (6.5 MUm). The frequency coverage (580 cm(-1)) is about 46% of center frequency. PMID- 26368737 TI - Topological effects in anisotropy-induced nano-fano resonance of a cylinder. AB - We demonstrate that optical Fano resonance can be induced by the anisotropy of a cylinder rather than frequency selection under the resonant condition. A tiny perturbation in anisotropy can result in a giant switch in the principal optic axis near plasmon resonance. Such anisotropy-induced Fano resonance shows fast reversion between forward and backward scattering at the lowest-energy interference. The near and far fields of the particle change dramatically around Fano resonance. The topology of optical singular points and the trajectory of energy flux distinctly reveal the interaction between the incident wave and the localized surface plasmons, which also determine the far-field scattering pattern. The anisotropy-induced Fano resonance and its high sensitivity open new perspectives on light-matter interactions and promise potential applications in biological sensors, optical switches, and optomechanics. PMID- 26368738 TI - High sensitivity refractive index sensor based on a tapered small core single mode fiber structure. AB - A high sensitivity refractive index (RI) sensor based on a tapered small core single-mode fiber (SCSMF) structure sandwiched between two traditional single mode fibers (SMF28) is reported. The microheater brushing technique was employed to fabricate the tapered fiber structures with different waist diameters of 12.5, 15.0, and 18.8 MUm. Experiments demonstrate that the fiber sensor with a waist diameter of 12.5 MUm offers the best sensitivity of 19212.5 nm/RIU (RI unit) in the RI range of 1.4304 to 1.4320. All sensors fabricated in this Letter show good linearity in terms of the spectral wavelength shift versus changes in RI. Furthermore, the sensor with the best sensitivity to RI was also used to measure relative humidity (RH) without any coating materials applied to the fiber surface. Experimental results show that the spectral wavelength shift changes exponentially as the RH varies from 60% to 95%. A maximum sensitivity of 18.3 nm per relative humidity unit (RHU) was achieved in the RH range of 90.4% to 94.5% RH. PMID- 26368739 TI - Raman optical activity spectroscopy by visible-excited coherent anti-Stokes Raman scattering. AB - We developed a Raman optical activity (ROA) spectroscopic system with visible excited coherent anti-Stokes Raman scattering (CARS). A supercontinuum within the visible region was generated with a photonic crystal fiber pumped with both 532 and 1064 nm excitation, generating a multiplexed CARS-ROA spectrum covering the whole fingerprint region. In visible excitation, the CARS-ROA spectrum of (-) beta-pinene shows a higher contrast ratio of the chirality-induced signal to the achiral background than that of the previously reported near-infrared CARS-ROA spectrum. PMID- 26368740 TI - Tunable type II intracavity difference frequency generation at 5.4 MUm in a two chip vertical external cavity surface emitting laser. AB - We report on the generation and experimental demonstration of intracavity type II difference frequency generation in a two chip InGaAs/GaAs vertical external cavity surface emitting laser. The presented two chip cavity provides two orthogonally polarized, independently tunable, high-intensity lasing modes with emissions around 970 and 1170 nm. A silver thiogallate nonlinear crystal is inserted in the common collinear folded region of the cavity to generate output in the mid-IR spectral band. The independent tunability of each fundamental color allows for more than 100 nm of tuning around a 5.4 MUm difference frequency generated signal with a CW output power in excess of 5 mW. PMID- 26368741 TI - Mid-infrared 333 MHz frequency comb continuously tunable from 1.95 to 4.0 MUm. AB - We report a 333 MHz femtosecond optical parametric oscillator in which carrier envelope offset stabilization was implemented by using a versatile locking technique that allowed the idler comb to be tuned continuously over the mid infrared range from 1.95 to 4.0 MUm. A specially designed multi-section, multi grating, periodically poled KTP crystal provided simultaneously phase-matched parametric down-conversion and pump + idler sum-frequency generation, enabling strong heterodyne signals with the pump supercontinuum (employed for locking) to be obtained across the tuning range of the device. The idler comb offset was stabilized to a 10 MHz reference frequency with a cumulative phase noise from 1 Hz-64 kHz of <1.3 rad maintained across the entire operating range, and average idler output powers up to 50 mW. PMID- 26368742 TI - Observation of stable-vector vortex solitons. AB - We report on the first experimental observation of stable-vector vortex solitons in nonlocal nonlinear media with a reorientational response, such as nematic liquid crystals. These solitons consist of two co-polarized, mutually trapped beams of different colors, a bright fundamental spatial soliton, and a nonlinear optical vortex. The nonlinear vortex component, which is normally unstable in nonlinear media, is stabilized and confined here by the highly nonlocal refractive potential induced by the soliton. PMID- 26368743 TI - Mid-infrared multi-mode absorption spectroscopy using interband cascade lasers for multi-species sensing. AB - An interband cascade laser (ICL) operating at 3.7 MUm has been used to perform multimode absorption spectroscopy, MUMAS, at scan rates up to 10 kHz. Line widths of individual modes in the range 10-80 MHz were derived from isolated lines in the MUMAS signatures of HCl. MUMAS data for methane covering a spectral range of 30 nm yielded a detection level of 30 MUbar.m for 1 s measurement time at 100 Hz. Simultaneous detection of methane, acetylene, and formaldehyde in a gas mixture containing all three species is reported. PMID- 26368745 TI - Acousto-optic Q-switching laser performance of Yb:GdCa(4)O(BO(3))(3)crystal. AB - We report on the active Q-switching laser performance of Yb:GdCa4O(BO3)3 crystal, demonstrated by employing an acousto-optic Q-switch in a compact plano-concave resonator. Stable repetitively Q-switched operation is achieved with pulse repetition rates varying from 30 to 0.2 kHz, producing an average output power of 10.2 W at 1027.5 nm at 30 kHz of repetition rate, with an optical-to-optical efficiency of 30%. The maximum pulse energy generated at the lowest repetition rate of 0.2 kHz is 4.75 mJ, with a pulse width being 11 ns, gives rise to a peak power that amounts to 432 kW. PMID- 26368744 TI - Nine-year change in statistical design, profile, and success rates of Phase II oncology trials. AB - We investigated nine-year trends in statistical design and other features of Phase II oncology clinical trials published in 2005, 2010, and 2014 in five leading oncology journals: Cancer, Clinical Cancer Research, Journal of Clinical Oncology, Annals of Oncology, and Lancet Oncology. The features analyzed included cancer type, multicenter vs. single-institution, statistical design, primary endpoint, number of treatment arms, number of patients per treatment arm, whether or not statistical methods were well described, whether the drug was found effective based on rigorous statistical testing of the null hypothesis, and whether the drug was recommended for future studies. PMID- 26368746 TI - Hyperbola-parabola primary mirror in Cassegrain optical antenna to improve transmission efficiency. AB - An optical model with a hyperbola-parabola primary mirror added in the Cassegrain optical antenna, which can effectively improve the transmission efficiency, is proposed in this paper. The optimum parameters of a hyperbola-parabola primary mirror and a secondary mirror for the optical antenna system have been designed and analyzed in detail. The parabola-hyperbola primary structure optical antenna is obtained to improve the transmission efficiency of 10.60% in theory, and the simulation efficiency changed 9.359%. For different deflection angles to the receiving antenna with the emit antenna, the coupling efficiency curve of the optical antenna has been obtained. PMID- 26368747 TI - Measurement of lithium isotope ratio in various concentration samples using degenerate four-wave mixing. AB - Phase-conjugate degenerate four-wave mixing (PCDFWM), as a sub-Doppler spectroscopy technique, can be employed to selectively analyze Li isotopes. It is necessary to explore the optimal incident powers in order to measure the Li isotope ratio accurately. In this case, the power condition of PCDFWM signal is first investigated using samples with various concentrations. The results indicate that the power characteristic is intimately related to the sample concentration, and the optimal incident power conditions for different sample concentrations are different. Under their own optimized power conditions, we measured the Li7/Li6 isotope ratio in Li standard solutions of 500, 300, and 200 ng/ml. The corresponding results are, respectively, 11.571+/-0.003, 11.552+/ 0.003, and 11.582+/-0.004, which are in good agreement with the value calculated by atomic absorption spectroscopy. The information obtained from this study suggests that PCDFWM can be used to measure isotope ratios accurately in samples with different concentrations under suitable power conditions. PMID- 26368748 TI - Dual-wavelength extinction method for fast sizing of metal nanosphere ensembles. AB - We propose a simple dual-wavelength extinction (DWE) method to measure the average size of spherical metal nanoparticle (NP) ensembles. Unlike the spectroscopic methods that need to measure the full spectra of scattering and/or extinction to retrieve the NP size, the DWE method can estimate the NP size by measuring the light extinction at only two properly selected wavelengths and thus is useful for fast sizing of metal NP ensembles. The influences of the NP shape deviation and ensemble dispersancy on the measurement accuracy are analyzed and discussed in detail. An empirical correction procedure is established to compensate these influences to further improve accuracy. The feasibility and reliability of the DWE method are corroborated by experimentally measuring several typical gold spherical NP ensembles and comparing the results with those obtained by three other standard methods. The experimental results indicate satisfactory accuracy of the DWE method for measuring gold NPs from 30 to 100 nm by using two measurement wavelengths of 532 and 573 nm. The studies show that the DWE method is efficient, reliable, and easy to implement. It may find wide applications in the metrology of NPs. PMID- 26368749 TI - Investigation of fringing electric field effect on high-resolution blue phase liquid crystal spatial light modulator. AB - The fringing electric field effect which determines the performance of a high resolution blue phase liquid crystal spatial light modulator (BPLC-SLM) is investigated by numerical modeling. The BPLC-SLM is polarization-dependent due to the transverse electric field component. The physical mechanism of the phase profile properties for different polarization states is analyzed. General design issues related to the BPLC-SLM configuration and phase profile properties are discussed. Notably, the material parameters and cell gap thickness are both optimized to obtain a low operation voltage (V2pi=26.07 V). This work provides fundamental understanding for the feasibility of low operation voltage and high spatial resolution BPLC-SLM. PMID- 26368750 TI - Multiregion apodized photon sieve with enhanced efficiency and enlarged pinhole sizes. AB - A novel multiregion structure apodized photon sieve is proposed. The number of regions, the apodization window values, and pinhole sizes of each pinhole ring are all optimized to enhance the energy efficiency and enlarge the pinhole sizes. The design theory and principle are thoroughly proposed and discussed. Two numerically designed apodized photon sieves with the same diameter are given as examples. Comparisons have shown that the multiregion apodized photon sieve has a 25.5% higher energy efficiency and the minimum pinhole size is enlarged by 27.5%. Meanwhile, the two apodized photon sieves have the same form of normalized intensity distribution at the focal plane. This method could improve the flexibility of the design and the fabrication the apodized photon sieve. PMID- 26368751 TI - Microwave interrogated large core fused silica fiber Michelson interferometer for strain sensing. AB - A Michelson-type large core optical fiber sensor has been developed, which is designed based on the optical carrier-based microwave interferometry technique, and fabricated by using two pieces of 200-MUm diameter fused silica core fiber as two arms of the Michelson interferometer. The interference fringe pattern caused by the optical path difference of the two arms is interrogated in the microwave domain, where the fringe visibility of 40 dB has easily been obtained. The strain sensing at both room temperature and high temperatures has been demonstrated by using such a sensor. Experimental results show that this sensor has a linear response to the applied strain, and also has relatively low temperature-strain cross talk. The dopant-free quality of the fused silica fiber provides high possibility for the sensor to have promising strain sensing performance in a high temperature environment. PMID- 26368752 TI - Preparation of Fe-doped colloidal SiO(2) abrasives and their chemical mechanical polishing behavior on sapphire substrates. AB - Abrasives are one of key influencing factors on surface quality during chemical mechanical polishing (CMP). Silica sol, a widely used abrasive in CMP slurries for sapphire substrates, often causes lower material removal rate (MRRs). In the present paper, Fe-doped colloidal SiO2 composite abrasives were prepared by a seed-induced growth method in order to improve the MRR of sapphire substrates. The CMP performance of Fe-doped colloidal SiO2 abrasives on sapphire substrates was investigated using UNIPOL-1502 CMP equipment. Experimental results indicate that the Fe-doped colloidal SiO2 composite abrasives exhibit lower surface roughness and higher MRR than pure colloidal SiO2 abrasives for sapphire substrates under the same testing conditions. Furthermore, the acting mechanism of Fe-doped colloidal SiO2 composite abrasives in sapphire CMP was analyzed by x-ray photoelectron spectroscopy. Analytical results show that the Fe in the composite abrasives can react with the sapphire substrates to form aluminum ferrite (AlFeO3) during CMP, which promotes the chemical effect in CMP and leads to improvement of MRR. PMID- 26368753 TI - Wearable telescopic contact lens. AB - We describe the design, fabrication, and testing of a 1.6 mm thick scleral contact lens providing both 1* and 2.8* magnified vision paths, intended for use as a switchable eye-borne telescopic low-vision aid. The F/9.7 telescopic vision path uses an 8.2 mm diameter annular entrance pupil and 4 internal reflections in a polymethyl methacrylate precision optic. This gas-impermeable insert is contained inside a smooth outer casing of rigid gas-permeable polymer, which also provides achromatic correction for refraction at the curved lens face. The unmagnified F/4.1 vision path is through the central aperture of the lens, with additional transmission between the annular telescope rings to enable peripheral vision. We discuss potential solutions for providing oxygenation for an extended wear version of the lens. The prototype lenses were characterized using a scale model human eye, and telescope functionality was confirmed in a small-scale clinical (nondispensed) demonstration. PMID- 26368754 TI - High-resolution fiber profilometer for hard-to-access areas. AB - A fiber-based profilometer is developed to measure hard-to-access areas. This system utilizes the low-coherence light interferometry technique to detect the internal surface profiles of some samples. A differentiation method is employed to enhance the lateral and vertical resolutions of the measured imaging results. The probe design parameters are optimized for a desired working distance and a small beam size. The performance of the profilometer system, especially its high resolution property, is demonstrated. PMID- 26368755 TI - On-orbit calibration of Visible Infrared Imaging Radiometer Suite reflective solar bands and its challenges using a solar diffuser. AB - The reflective solar bands (RSBs) of the Visible Infrared Imaging Radiometer Suite (VIIRS) on board the Suomi National Polar-Orbiting Partnership satellite are calibrated by a solar diffuser (SD) panel whose performance is itself monitored by an accompanying solar diffuser stability monitor (SDSM). In this comprehensive work we describe the SD-based calibration algorithm of the RSBs, analyze the calibration data, and derive the performance results-the RSB calibration coefficients or F-factors-for the current three and a half years of mission. The application of the newly derived product of the SD bidirectional reflectance factor and the vignetting function for the SD screen and the newly derived SD degradation, so-called H-factors, effectively minimizes the artificial seasonal patterns in the RSB calibration coefficients due to the errors of these ingredient inputs. The full illumination region, the "sweet spot," during calibration events for SD view is carefully examined and selected to ensure high data quality and to reduce noise owing to non-fully illuminated samples. A time dependent relative spectral response (RSR), coming from the large out-of-band contribution and the VIIRS optical system wavelength-dependent degradation, is derived from an iterative approach and applied in the SD calibration for each RSB. The result shows that VIIRS RSBs degrade much faster at near-infrared (NIR) and shortwave-infrared (SWIR) wavelength ranges due to the faster degradation of the rotating telescope assembly against the remaining part of the system. The gains of the VIIRS RSBs have degraded 2.0% (410 nm, Band M1), 0.2% (443 nm, Band M2), -0.3% (486 nm, Band M3), 0.2% (551 nm, Band M4), 6.2% (640 nm, Band I1), 11.0% (671 nm, Band M5), 21.3% (745 nm, Band M6), 35.8% (862 nm, Band I2), and 35.8% (862 nm, Band M7), respectively, since launch and 24.8% (1238 nm, Band M8), 18.5% (1378 nm, Band M9), 11.5% (1610 nm, Band I3), 11.5% (1610, Band M10), and 4.0% (2250 nm, Band M11), respectively, since 20 January 2012. It is established that the SD calibration accurately catches the on-orbit RSB degradation according to the instrument design and the calibration algorithm. However, due to the inherent nonuniform degradation of the SD affecting especially the short wavelength bands and the lack of capability of the SDSM calibration to catch degradation beyond 935 nm, the direct and the unmitigated application of the SD calibration result will introduce nonnegligible error into the calibration coefficients resulting in long-term drifts in the sensor data records and consequently the high-level products. We explicitly unveil the effect of the nonuniformity in SD degradation in the RSB calibration coefficients but also briefly discuss a critical yet simple mitigation to restore the accuracy of the calibration coefficients based on lunar observations. The methodology presented here thus remains intact as the cornerstone of the RSB calibration, and our derived RSB calibration coefficients represent the optimal result. This work has the most impact on the quality of the ocean color products that sensitively depend on the moderate visible and NIR bands (M1-M7), as well as the SWIR bands (M8, M10, and M11). PMID- 26368756 TI - Broadband wavelength and angle-resolved scattering characterization for nanophotonics investigations. AB - The characterization of scattered light is complex and relatively nonstandardized despite being of great importance to many optical technologies. While total scatter can be efficiently measured using integrating-sphere-based techniques, a detailed determination of the full bidirectional scattering distribution function is far more challenging, often requiring complicated and expensive equipment as well as substantial measurement time. Due to this, many research groups rely on simpler, angle-resolved scattering (ARS) measurements, yet these are typically carried out using a single wavelength source, therefore providing limited information. Here, we demonstrate a custom-built broadband angle-resolved optical spectrometer, which utilizes a supercontinuum white light laser source combined with a custom automated goniometer and a Si CCD array spectrometer in order to carry out broad spectral measurements of ARS. The use of a collimated supercontinuum allows for small area measurements that are often crucial for investigation of nanophotonic samples created using expensive fabrication techniques. The system has been tested and calibrated, and accuracy and reproducibility have been verified by integrating wavelength and ARS data over the angular range and comparing to calibrated integrating sphere measurements. PMID- 26368757 TI - Direct measurements of temperature-dependent laser absorptivity of metal powders. AB - A compact system is developed to measure laser absorptivity for a variety of powder materials (metals, ceramics, etc.) with different powder size distributions and thicknesses. The measured results for several metal powders are presented. The results are consistent with those from ray tracing calculations. PMID- 26368758 TI - Efficient scheme for mid-infrared generation using simultaneous optical parametric oscillators and DFG processes in a double-pass pump configuration. AB - We present numerical results of an efficient scheme for mid-infrared generation using simultaneous quasi-phase matched optical parametric oscillators (OPO) and difference-frequency generation (DFG) processes in a singly resonant cavity with double-pass pump configuration. Considering an appropriately poled grating structure in MgO doped congruent lithium niobate, we have shown that it is possible to realize the double-pass pump singly resonant (DPSR) cavity configuration for the simultaneous OPO+DFG process, unlike the cascaded interaction scheme, leading to efficient mid-IR generation. Our numerical results are in agreement with the recently reported experimental results. We also present optimum parameters for the DPSR cavity configuration that could provide maximum conversion efficiency. PMID- 26368759 TI - Self-calibration and laser energy monitor validations for a double-pulsed 2-MUm CO2 integrated path differential absorption lidar application. AB - Double-pulsed 2-MUm integrated path differential absorption (IPDA) lidar is well suited for atmospheric CO2 remote sensing. The IPDA lidar technique relies on wavelength differentiation between strong and weak absorbing features of the gas normalized to the transmitted energy. In the double-pulse case, each shot of the transmitter produces two successive laser pulses separated by a short interval. Calibration of the transmitted pulse energies is required for accurate CO2 measurement. Design and calibration of a 2-MUm double-pulse laser energy monitor is presented. The design is based on an InGaAs pin quantum detector. A high-speed photoelectromagnetic quantum detector was used for laser pulse profile verification. Both quantum detectors were calibrated using a reference pyroelectric thermal detector. Calibration included comparing the three detection technologies in the single-pulsed mode, then comparing the quantum detectors in the double-pulsed mode. In addition, a self-calibration feature of the 2-MUm IPDA lidar is presented. This feature allows one to monitor the transmitted laser energy, through residual scattering, with a single detection channel. This reduces the CO2 measurement uncertainty. IPDA lidar ground validation for CO2 measurement is presented for both calibrated energy monitor and self-calibration options. The calibrated energy monitor resulted in a lower CO2 measurement bias, while self-calibration resulted in a better CO2 temporal profiling when compared to the in situ sensor. PMID- 26368760 TI - Polarization-based balanced detection for spectral-domain optical coherence tomography. AB - We present a new design for spectral-domain optical coherence tomography that allows balanced detection using a single camera. The design uses polarization optics to encode the light in reference and sample arms. Two parallel and highly aligned spectra, which carry out-of-phase interference signals, in-phase common noise, and auto-interference terms, are focused on the camera, which performs the digital balanced detection for each wavelength. The optical system is characterized and tested for tissue imaging. Results demonstrate consistent signal gains in depth and suppression of DC and sample auto-interference. The design could be further amended for polarization-sensitive imaging and might demonstrate a market for manufacturing dual-line cameras with analog-balanced detection capability. PMID- 26368761 TI - 560 W all fiber and polarization-maintaining amplifier with narrow linewidth and near-diffraction-limited beam quality. AB - We present a narrow linewidth, all-fiber polarization-maintained amplifier chain seeded by a phase-modulated single-frequency laser, which is a narrow linewidth. Different from previous phase-modulation techniques, the phase-modulation signal is generated by simply imposing an excited signal to an acoustic-optical driven source. Theoretical simulation results show that this method can suppress stimulated Brillouin scattering (SBS) to a better degree, and the output power can be boosted to about 1.2 kW in terms of the SBS threshold. By amplifying the phase-modulated seed based on master-oscillator power-amplification configuration in experiments, a 560 W output laser is achieved with slope efficiency of 87.2% and linewidth of <5 GHz. Further power scaling is limited by mode instability instead of an SBS effect. At maximal output power, the beam quality (M2 factor) and polarization extinction ratio is measured to be within 1.3 and 14 dB, respectively. PMID- 26368763 TI - Generalized Fibonacci photon sieves. AB - We successfully extend the standard Fibonacci zone plates with two on-axis foci to the generalized Fibonacci photon sieves (GFiPS) with multiple on-axis foci. We also propose the direct and inverse design methods based on the characteristic roots of the recursion relation of the generalized Fibonacci sequences. By switching the transparent and opaque zones, according to the generalized Fibonacci sequences, we not only realize adjustable multifocal distances but also fulfill the adjustable compression ratio of focal spots in different directions. PMID- 26368762 TI - Spectral attenuation and backscattering as indicators of average particle size. AB - Measurements of the particulate beam attenuation coefficient at multiple wavelengths in the ocean typically exhibit a power law dependence on wavelength, and the slope of that power law has been related to the slope of the particle size distribution (PSD), when assumed to be a power law function of particle size. Recently, spectral backscattering coefficient measurements have been made using sensors deployed at moored observatories, on autonomous underwater vehicles, and even retrieved from space-based measurements of remote sensing reflectance. It has been suggested that these backscattering measurements may also be used to obtain information about the shape of the PSD. In this work, we directly compared field-measured PSD with multispectral beam attenuation and backscattering coefficients in a coastal bottom boundary later. The results of this comparison demonstrated that (1) the beam attenuation spectral slope correlates with the average particle size as suggested by theory for idealized particles and PSD; and (2) measurements of spectral backscattering also contain information reflective of the average particle size in spite of large deviations of the PSD from a spectral power law shape. PMID- 26368764 TI - Gradient-based inverse extreme ultraviolet lithography. AB - Extreme ultraviolet (EUV) lithography is the most promising successor of current deep ultraviolet (DUV) lithography. The very short wavelength, reflective optics, and nontelecentric structure of EUV lithography systems bring in different imaging phenomena into the lithographic image synthesis problem. This paper develops a gradient-based inverse algorithm for EUV lithography systems to effectively improve the image fidelity by comprehensively compensating the optical proximity effect, flare, photoresist, and mask shadowing effects. A block based method is applied to iteratively optimize the main features and subresolution assist features (SRAFs) of mask patterns, while simultaneously preserving the mask manufacturability. The mask shadowing effect may be compensated by a retargeting method based on a calibrated shadowing model. Illustrative simulations at 22 and 16 nm technology nodes are presented to validate the effectiveness of the proposed methods. PMID- 26368765 TI - Laser echo signal amplification in a turbulent atmosphere. AB - A lidar system for registration of laser return amplification in a turbulent atmosphere due to backscatter amplification effect is considered in this paper. In the system, two receiving channels are used. One of them (axial) coincides with the transmitter channel, while another channel (nonaxial) receives the backscattered radiation at a small angle to the probing beam axis. The power ratio of the echo signal recorded in the axial channel to that recorded in the nonaxial one is a measure of the return amplification. The results of long duration lidar atmospheric experiments show that the power of the echo signal registered in the axial channel usually exceeds that in the nonaxial one. PMID- 26368766 TI - Reducing coherent noise in interference systems using the phase modulation technique. AB - The phase modulation technique is adopted to reduce the coherent noise that arises from spurious interference. By choosing an appropriate driving signal, the method can reduce the coherent function of coherent noise to a great degree while keeping the coherent function of a coherent signal nearly unchanged. Simulation results show that for the grating interferometer, the phase error caused by coherent noise is reduced by 81.53% on average. For the Twyman interferometer, the fringe quality and contrast deteriorated by coherent noise are significantly improved. Furthermore, an experiment is set up in the phase-modulated Twyman interferometer to verify the feasibility of the principle. It is concluded that the method is effective to reduce the coherent noise in interference systems. PMID- 26368767 TI - Three-dimensional imaging through scattering media using three-dimensionally coded pattern projection. AB - We propose a method for visualizing three-dimensional objects in scattering media. Our method is based on active illumination using three-dimensionally coded patterns and a numerical algorithm employing a sparsity constraint. We experimentally demonstrated the proposed imaging method for test charts located three-dimensionally at different depths in the space behind a translucent sheet. PMID- 26368768 TI - Precise autofocus method employing normalized fluorescence image size in a two photon polymerization nanofabrication system. AB - The autofocus method has been investigated to improve the precise positioning of a substrate surface at the center of the laser focal spot in two-photon polymerization (TPP) nanofabrication. For this purpose, we developed a novel autofocus method using normalized image size, which was calculated with the second momentum radius (SMR) of two-photon induced fluorescence (TPIF). The SMR of TPIF was theoretically analyzed and experimentally compared with the average intensity of TPIF for various input laser powers. The results show that the proposed method enhanced the precision and robustness of autofocus in TPP. Specifically, the experimental creation of ascending voxel arrays demonstrated both the method's immunity to input laser power change, and a high precision of +/-0.045 MUm. To test the practical feasibility of the proposed autofocus method, 300 MUm*260 MUm single-layer honey-comb structures were successfully fabricated with precompensation and dynamic compensation using the proposed autofocus method. PMID- 26368769 TI - Phase sensitivity to temperature of the guiding mode in polarization-maintaining photonic crystal fiber. AB - The propagating phase changing of a polarization-maintaining photonic crystal fiber (PM-PCF) caused by temperature variation is theoretically studied, as well as compared with conventional PANDA fiber. As to verifying numerical analysis, a platform based on a Michelson interferometer for phase versus temperature measurement was built for both kinds of fiber. Experiments show that PM-PCF has similar temperature sensitivity with conventional polarization-maintaining fiber. With optimized PM-PCF design (thinner coating layer and coating material with smaller thermal expansion coefficient), the sensitivity could be further reduced to about 80% of the present level. PMID- 26368770 TI - Backscatter near-end solution in processing of scanning lidar data. AB - The significant issue of the classic multiangle data-processing technique is that the height up to which this technique allows the reliable profiling of the searched atmosphere is always significantly less than the maximum operative range of the scanning lidar signals. The existing multiangle inversion methodology does not allow for the proper inversion into optical profiles of the distant range signals measured in and close to zenith. In this study, a data-processing technique is considered which allows for increasing the maximal heights when profiling the atmosphere with scanning lidar; it is achieved by using the auxiliary backscatter near-end solution and the assumption of a constant lidar ratio over high altitudes. Simulated and experimental data are presented that illustrate the specifics of such a combined technique. PMID- 26368771 TI - Detection of toxic elements using laser-induced breakdown spectroscopy in smokers' and nonsmokers' teeth and investigation of periodontal parameters. AB - A laser-induced breakdown spectrometer (LIBS) was built and optimized to detect levels of toxic elements such as lead, cadmium, and arsenic present in the roots of extracted teeth of smokers and nonsmokers. Sixty extracted teeth from patients having a history of chronic periodontitis were divided into two groups of 30 teeth each for smoker and nonsmoker patients and, as controls, a third group of 30 patients who did not have a history of chronic periodontitis. The respective elemental concentration (Pb, Cd, and As) 23-29, 0.26-0. 31, and 0.64-11 ppm are for nonsmokers, 35-55, 0.33-0.51, and 0.91-1.5 ppm are for smokers, and lastly 0.17-0.31, 0.01-0.05, and 0.05-0.09 ppm are for control group. In order to test the validity of the results achieved using our LIBS system, a standard inductively coupled plasma (ICP) technique was also applied for the analysis of the same teeth samples, and ICP results were found to be in excellent agreement with our LIBS results. In addition to this, the gingival index, plaque index, clinical attachment loss (CAL) and probing pocket depth were also recorded. Our LIBS spectroscopic analysis showed high levels of lead, cadmium, and arsenic concentration on root surfaces of teeth, which may be due to CAL. PMID- 26368772 TI - Design of a pentagonal photonic crystal fiber with high birefringence and large flattened negative dispersion. AB - Novel pentagonal photonic crystal fiber with high birefringence, large flattened negative dispersion, and high nonlinearity is proposed. The dispersion and birefringence properties of this structure are simulated and analyzed numerically based on the full vector finite element method (FEM). Numerical results indicate that the fiber obtains a large average dispersion of -611.9 ps/nm/km over 1,460 1,625 nm and -474 ps/nm/km over 1425-1675 nm wavelength bands for two kinds of optimized designs, respectively. In addition, the proposed PCF shows a high birefringence of 1.67*10-2 and 1.75*10-2 at the operating wavelength of 1550 nm. Moreover, the influence of the possible variation in the parameters during the fabrication process on the dispersion and birefringence properties is studied. The proposed PCF would have important applications in polarization maintaining transmission systems, residual dispersion compensation, supercontinuum generation, and the design of widely tunable wavelength converters based on four-wave mixing. PMID- 26368773 TI - Millijoule femtosecond micro-Bessel beams for ultra-high aspect ratio machining. AB - We report on a functional experimental design for Bessel beam generation capable of handling high-energy ultrashort pulses (up to 1.2 mJ per pulse of 50 fs duration). This allows us to deliver intensities exceeding the breakdown threshold for air or any dielectric along controlled micro-filaments with lengths exceeding 4 mm. It represents an unprecedented upscaling in comparison to recent femtosecond Bessel beam micromachining experiments. We produce void microchannels through glass substrates to demonstrate that aspect ratios exceeding 1200?1 can be achieved by using single high-intensity pulses. This demonstration must lead to new methodologies for deep-drilling and high-speed cutting applications. PMID- 26368774 TI - Fabrication, characterization, and applications of microlenses. AB - Microlenses (MLs) and microlens arrays (MLAs) are assuming an increasingly important role in optical devices. In response to this rapid evolution in technology, emphasis is being placed on research into new manufacturing methods for these devices as well as the characterization of their performance. This paper provides an overview of the fabrication of MLs and MLAs by electrical, mechanical, chemical, and optical methods. As each processing method has distinct advantages and limitations, the most significant characteristic parameters and the measurement of these parameters are discussed for each method. These parameters are then used as indices to evaluate and improve each of the processing methods. Some examples of practical applications of MLAs, especially for micromechanical optoelectronic devices, are also given. This paper aims to summarize the present development and the state of the art in processing technology of MLs and MLAs. PMID- 26368775 TI - Static spectropolarimeter concept adapted to space conditions and wide spectrum constraints. AB - Issues related to moving elements in space and instruments working in broader wavelength ranges lead to the need for robust polarimeters that are efficient on a wide spectral domain and adaptable to space conditions. As part of the UVMag consortium, which was created to develop spectropolarimetric UV facilities in space, such as the Arago mission project, we present an innovative concept of static spectropolarimetry. We studied a static and polychromatic method for spectropolarimetry, which is applicable to stellar physics. Instead of temporally modulating the polarization information, as is usually done in spectropolarimeters, the modulation is performed in a spatial direction, orthogonal to the spectral one. Thanks to the proportionality between phase retardance imposed by a birefringent material and its thickness, birefringent wedges can be used to create this spatial modulation. The light is then spectrally cross dispersed, and a full Stokes determination of the polarization over the whole spectrum can be obtained with a single-shot measurement. The use of magnesium fluoride wedges, for example, could lead to a compact, static polarimeter working at wavelengths from 0.115 up to 7 MUm. We present the theory and simulations of this concept as well as laboratory validation and a practical application to Arago. PMID- 26368776 TI - Pseudo-cat's eye for improved tilt-immune interferometry. AB - We present a new simple optical design for a cat's eye retroreflector. We describe the design of the new optical configuration and its use in tilt-immune interferometry where it enables the tracking of the displacement of a plane target mirror with minimum sensitivity to its tilt about axes orthogonal to the interferometer's optical axis. In this application the new cat's eye does not behave as a perfect retroreflector and we refer to it as a "pseudo"-cat's eye (PCE). The device allows, for the first time, tilt-immune interferometric displacement measurements in cases where the nominal distance to the target mirror is significantly larger than the length of the cat's eye. We describe the general optical characteristics of the PCE and compare its performance in our application with that of a conventional cat's eye optical configuration using ABCD matrices and Zemax analyses. We further suggest a simple modification to the design that would enable the PCE to behave as a perfect cat's eye, and this design may provide an advantageous solution for other applications. PMID- 26368777 TI - Multi-spectral infrared spectroscopy for robust plastic identification. AB - The identification and classification of plastics plays an important role in waste management and recycling processes. Present electrical and optical sorting techniques lack the required resolution for accurate identification in a high throughput manner for a diverse set of plastics commonly found in municipal waste. In this work a multi-spectral infrared spectroscopic technique is employed to construct a unique fingerprint library of 12 plastic resin groups that are commonly encountered in municipal waste. We test the proposed method in a blind plastic identification experiment, which shows excellent unbiased identification accuracy. This simple optical technique in combination with the multi-spectral library will enable high throughput and accurate detection of various plastics from recovered solid waste. PMID- 26368778 TI - Study of the impact of truncations on wedge waves by using the laser ultrasound technique. AB - This research focuses on measuring the impact of truncations on the dispersion characteristics of wedge waves propagating along the wedge tip by using the laser generated ultrasound. First, the finite element method was used to simulate laser induced wedge waves and the dispersion curves were obtained by using the 2D Fourier transformation method. Pulsed laser excitation and laser-based wedge wave detection were also utilized to investigate these characteristics experimentally. For the 20 degrees and 60 degrees line wedges, both experimental and numerical results indicated that a nonideal wedge tip had great impact on the wedge waves. The modes of the 20 degrees line wedge with truncations presented anomalous dispersion, low mode closed to high mode in high frequency, and the characteristics of antisymmetric Lamb waves as truncation increased. Meanwhile, the modes of the 60 degrees line wedge with truncations showed the characteristics of antisymmetric Lamb waves, and the A1 mode was also observed clearly. The findings of this study can be used to evaluate and detect wedge structure. PMID- 26368779 TI - Femtosecond pulsed laser ablation of polyimide at oblique angles for medical applications. AB - We report the ablation results for surface modification of polyimide Kapton HN foils using ultrashort femtosecond laser pulses. The modification threshold fluences for 75 MUm thick films of polyimide were determined at different incident angles (0 degrees , 20 degrees , 30 degrees , 45 degrees , and 50 degrees ) for vertical and horizontal diameters. Ablation at oblique angles was investigated as such interactions are found during laser procedures with the eye that require scanning of the beam and are very important to know for the treatment of various eye diseases. Polyimide, in this study, was considered as a model for corneal sculpting. Use of ultrashort femtosecond laser pulses for high precision patterning of the sample, without thermal damage to the surroundings, has been investigated. The relationship between the incidence angle with ablation threshold fluence, threshold energy, and beam radius are described. Also, threshold energies and threshold fluences for different thicknesses of polyimide were investigated. PMID- 26368780 TI - Miniature endoscopic optical coherence tomography for calculus detection. AB - The effective treatment of periodontitis involves the detection and removal of subgingival dental calculus. However, subgingival calculus is more difficult to detect than supragingival calculus because it is firmly attached to root surfaces within periodontal pockets. To achieve a smooth root surface, clinicians often remove excessive amounts of root structure because of decreased visibility. In addition, enamel pearl, a rare type of ectopic enamel formation on the root surface, can easily be confused with dental calculus in the subgingival environment. In this study, we developed a fiber-probe swept-source optical coherence tomography (SSOCT) technique and combined it with the quantitative measurement of an optical parameter [standard deviation (SD) of the optical coherence tomography (OCT) intensity] to differentiate subgingival calculus from sound enamel, including enamel pearl. Two-dimensional circumferential images were constructed by rotating the miniprobe (0.9 mm diameter) while acquiring image lines, and the adjacent lines in each rotation were stacked to generate a three dimensional volume. In OCT images, compared to sound enamel and enamel pearls, dental calculus showed significant differences (P<0.001) in SD values. Finally, the receiver operating characteristic curve had a high capacity (area under the curve=0.934) for discriminating between healthy regions (including enamel pearl) and dental calculus. PMID- 26368781 TI - Optimization of GRIN lens Stokes polarimeter. AB - In a recent study we reported on the gradient index (GRIN) lens Stokes polarimeter (GLP) [Opt. Lett.39, 2656 (2014)10.1364/OL.39.002656OPLEDP0146-9592]. With a simple architecture, this polarimeter can measure the state of polarization in a single shot. In this article, we present further studies for improving the performance of the GLP. Detailed discussions are presented on the optimization process of the GLP based on different choices of data from the CCD images. It is pointed out that many optimization techniques, although developed for other types of Stokes polarimeters, can also be applied to the GLP because the GRIN lens can traverse all possible retardance and fast axis modulations. PMID- 26368782 TI - Optimal design of tilt carrier frequency computer-generated holograms to measure aspherics. AB - Computer-generated holograms (CGHs) provide an approach to high-precision metrology of aspherics. A CGH is designed under the trade-off among size, mapping distortion, and line spacing. This paper describes an optimal design method based on the parametric model for tilt carrier frequency CGHs placed outside the interferometer focus points. Under the condition of retaining an admissible size and a tolerable mapping distortion, the optimal design method has two advantages: (1) separating the parasitic diffraction orders to improve the contrast of the interferograms and (2) achieving the largest line spacing to minimize sensitivity to fabrication errors. This optimal design method is applicable to common concave aspherical surfaces and illustrated with CGH design examples. PMID- 26368783 TI - Cell shape identification using digital holographic microscopy. AB - We present a cost-effective, simple, and fast digital holographic microscopy method based upon Rayleigh-Sommerfeld backpropagation for identification of the geometrical shape of a cell. The method was tested using synthetic hologram images generated by ray-tracing software and from experimental images of semitransparent spherical beads and living red blood cells. Our results show that, by only using the real part of the back-reconstructed amplitude, the proposed method can provide information of the geometrical shape of the object and at the same time accurately determine the axial position of the object under study. The proposed method can be used in flow chamber assays for pathophysiological studies where fast morphological changes of cells are studied in high numbers and at different heights. PMID- 26368784 TI - Interferometric nulling of four channels with integrated optics. AB - Nulling interferometry has been identified as a competitive technique for the detection of extrasolar planets. In its basic form, the technique consists of combining out-of-phase a single pair of telescopes to effectively null the light of a bright star and reveal the dim glow of the companion. However, in order to mitigate the effect of the stellar leaks through the interferometer, a broad angular central null is required. The hierarchical combination of several pairs of telescopes can accomplish this task. We have manufactured and tested with monochromatic light an integrated optics component, which combines a linear array of four telescopes in the nulling mode envisaged by Angel and Woolf [Astroph. J.475, 373-379 (1997).10.1086/apj.1997.475.issue-1ASJOAB0004-637X]. By simulating in the laboratory the motion of a star in the sky, we could measure the expected angular transmission of the four-telescope nuller. Moreover, the tests have demonstrated a broad nulling scaling as the fourth power of the baseline delay. PMID- 26368785 TI - Graphene-based electromagnetically induced transparency with coupling Fabry-Perot resonators. AB - We investigate the plasmonic analog of electromagnetically induced transparency (EIT) using two adjacent graphene-based Fabry-Perot (F-P) resonators side coupling to a nanoribbon waveguide. By the coupling mode theory in time and F-P resonant model, the destructive interference from the coupling of the two F-P resonators results in the EIT-like optical response. The induced peak and width of the transparency window can be dynamically manipulated by varying the coupling distance of the two resonators, and the transparent window is easily shifted by tuning the resonator length or the chemical potential of the graphene nanoribbon. In order to verify the characteristics of slow light, the group index profile is analyzed at different coupling distances. The proposed graphene-based EIT-like system could open up new opportunities for potential applications in plasmonic slow light and optical information buffering devices. PMID- 26368786 TI - Snake-assisted quality-guided phase unwrapping for discontinuous phase fields. AB - Quality-guided phase unwrapping (QGPU) has been proven as an effective phase unwrapping method. As the QGPU assumes that the true phase map is continuous, it suffers from the discontinuity problem. To solve this problem, the windowed Fourier transform (WFT) based methods have been adopted to obtain effective quality measures. Nevertheless, in some special cases, using the quality maps from the WFT-based methods could not lead to a correct result. In this paper, we propose a method that incorporates the GVF snake model to assist the unwrapping process. This new method achieves better results than using the WFT-based methods directly in some discontinuous examples. PMID- 26368787 TI - Assessing the economic value of avoiding hospital admissions by shifting the management of gram+ acute bacterial skin and skin-structure infections to an outpatient care setting. AB - OBJECTIVE: To estimate, from a US payer perspective, the cost offsets of treating gram positive acute bacterial skin and skin-structure infections (ABSSSI) with varied hospital length of stay (LOS) followed by outpatient care, as well as the cost implications of avoiding hospital admission. METHODS: Economic drivers of care were estimated using a literature-based economic model incorporating inpatient and outpatient components. The model incorporated equal efficacy, adverse events (AE), resource use, and costs from literature. Costs of once- and twice-daily outpatient infusions to achieve a 14-day treatment were analyzed. Sensitivity analyses were performed. Costs were adjusted to 2015 US$. RESULTS: Total non-drug medical cost for treatment of ABSSSI entirely in the outpatient setting to avoid hospital admission was the lowest among all scenarios and ranged from $4039-$4924. Total non-drug cost for ABSSSI treated in the inpatient setting ranged from $9813 (3 days LOS) to $18,014 (7 days LOS). Inpatient vs outpatient cost breakdown was: 3 days inpatient ($6657)/11 days outpatient ($3156-$3877); 7 days inpatient ($15,017)/7 days outpatient ($2495-$2997). Sensitivity analyses revealed a key outpatient cost driver to be peripherally inserted central catheter (PICC) costs (average per patient cost of $873 for placement and $205 for complications). LIMITATIONS: Drug and indirect costs were excluded and resource use was not differentiated by ABSSSI type. It was assumed that successful ABSSSI treatment takes up to 14 days per the product labels, and that once-daily and twice-daily antibiotics have equal efficacy. CONCLUSION: Shifting ABSSSI care to outpatient settings may result in medical cost savings greater than 53%. Typical outpatient scenarios represent 14-37% of total medical cost, with PICC accounting for 28-43% of the outpatient burden. The value of new ABSSSI therapies will be driven by eliminating the need for PICC line, reducing length of stay and the ability to completely avoid a hospital stay. PMID- 26368788 TI - Pseudoprogression after proton radiotherapy for pediatric low grade glioma. PMID- 26368789 TI - CRIB scores as a tool for assessing risk for the development of pulmonary hypertension in extremely preterm infants with bronchopulmonary dysplasia. AB - OBJECTIVE: Bronchopulmonary dysplasia (BPD) increases the risk for developing pulmonary hypertension (PH). However, the risk factors associated with BPD associated PH remain unclear. Our primary aim was to determine perinatal risk factors associated with the development of PH in infants with BPD. STUDY DESIGN: We retrospectively reviewed medical records of 303 infants born at <= 28 weeks' gestation. Infants were categorized as having no, mild, moderate, or severe BPD. PH was diagnosed by echocardiogram. Data were analyzed using Fisher exact test, two-sample t-test, and multivariable logistic regression. RESULTS: The incidence of PH in our cohort was 12%. Infants with PH had lower birth weights and gestational ages (p < 0.001). After controlling for confounding variables, severe BPD (p < 0.001), and higher Clinical Risk Index for Babies (CRIB) scores (p = 0.04) were associated with the development of PH. CONCLUSION: Severe BPD increases the risk for developing PH. Higher CRIB scores correlate with PH development in infants with BPD. We speculate that CRIB scores may allow for early categorization of preterm infants with a higher likelihood of developing PH. PMID- 26368790 TI - B-type natriuretic peptide: biomarker of persistent pulmonary hypertension of the newborn? AB - OBJECTIVE: We assessed the utility of plasma B-type natriuretic peptide (BNP) in infants with persistent pulmonary hypertension of the newborn (PPHN) in the prediction of inhaled nitric oxide (iNO) requirement. METHODS: This prospective study involved neonates (gestational age >= 34 weeks) with PPHN and confirmatory echocardiographic findings. Plasma BNP was assayed once within 12 hours of meeting criteria for iNO requirements and twice every 24 to 48 hours thereafter. RESULTS: Infants requiring iNO (n = 14) had higher first BNP levels compared with others (n = 5) (455.5 +/- 350.6 vs. 30.1 +/- 25.3 ng/dL, p < 0.003). The sensitivity, specificity, positive and negative predictive values, and 95% confidence intervals (CI) for plasma BNP greater than 30 ng/dL to predict iNO requirement were 100 (85-100), 80 (37-80), 94 (80-94), and 100 (46-100)%, respectively. Corresponding values at a cut-off plasma BNP concentration greater than 85 ng/dL were 79 (62-79), 100 (53-100), 100 (79-100), and 63 (33-63)%, respectively. CONCLUSION: BNP had excellent sensitivity and negative predictive value for iNO requirement and above 30 ng/dl maybe a useful prognostic biomarker in PPHN. PMID- 26368791 TI - Application of Visible-to-UV Photon Upconversion to Photoredox Catalysis: The Activation of Aryl Bromides. AB - The activation of aryl-Br bonds was achieved by sequential combination of a triplet-triplet annihilation process of the organic dyes, butane-2,3-dione and 2,5-diphenyloxazole, with a single-electron-transfer activation of aryl bromides. The photophysical and chemical steps were studied by time-resolved transient fluorescence and absorption spectroscopy with a pulsed laser, quenching experiments, and DFT calculations. PMID- 26368792 TI - Sexual Recruitment in Zostera marina: Progress toward a Predictive Model. AB - Ecophysiological stress and physical disturbance are capable of structuring meadows through a combination of direct biomass removal and recruitment limitation; however, predicting these effects at landscape scales has rarely been successful. To model environmental influence on sexual recruitment in perennial Zostera marina, we selected a sub-tidal, light-replete study site with seasonal extremes in temperature and wave energy. During an 8-year observation period, areal coverage increased from 4.8 to 42.7%. Gains were stepwise in pattern, attributable to annual recruitment of patches followed by centrifugal growth and coalescence. Recruitment varied from 13 to 4,894 patches per year. Using a multiple linear regression approach, we examined the association between patch appearance and relative wave energy, atmospheric condition and water temperature. Two models were developed, one appropriate for the dispersal of naked seeds, and another for rafted flowers. Results indicated that both modes of sexual recruitment varied as functions of wind, temperature, rainfall and wave energy, with a regime shift in wind-wave energy corresponding to periods of rapid colonization within our site. Temporal correlations between sexual recruitment and time-lagged climatic summaries highlighted floral induction, seed bank and small patch development as periods of vulnerability. Given global losses in seagrass coverage, regions of recovery and re-colonization will become increasingly important. Lacking landscape-scale process models for seagrass recruitment, temporally explicit statistical approaches presented here could be used to forecast colonization trajectories and to provide managers with real-time estimates of future meadow performance; i.e., when to expect a good year in terms of seagrass expansion. To facilitate use as forecasting tools, we did not use statistical composites or normalized variables as our predictors. This study, therefore, represents a first step toward linking remotely acquired environmental data to sexual recruitment, an important measure of seagrass performance that translates directly into landscape-scale coverage change. PMID- 26368793 TI - Role of inflammatory mediators in patients with recurrent pregnancy loss. AB - OBJECTIVE: To examine interleukin-12 (IL-12), IL-18, IFN-gamma, intracellular adhesion molecule-1 (ICAM-1), leukemia inhibitory factor (LIF), and migration inhibitory factor (MIF) levels in precisely-timed blood and endometrial tissue samples from women with idiopathic recurrent pregnancy loss (RPL). DESIGN: Case control study. SETTING: University hospital. PATIENT(S): Twenty-one women with RPL and 20 women with proven fertility (controls). INTERVENTION(S): Primary endometrial cells and blood samples during the midsecretory phase (days 19-23). MAIN OUTCOME MEASURE(S): Detection of IL-12, IL-18, IFN-gamma, ICAM-1, LIF, and MIF via enzyme-linked immunosorbent assay in both blood and endometrial tissue samples. RESULT(S): The blood and tissue levels of IL-12, IL-18, and IFN-gamma were statistically significantly higher, and the blood and tissue levels of LIF and MIF were statistically significantly lower in patients with RPL. Only the level of tissue ICAM-1 was higher in patients with RPL. There was a strong correlation between blood and tissue level measurements of IL-12, IL-18, LIF, and MIF. CONCLUSION(S): Our findings support the hypothesis that inflammatory processes may contribute to pregnancy loss, possibly through their role in implantation. We found that blood and tissue levels of IL-18, LIF, and MIF, and tissue levels of IL-12, IFN-gamma, and ICAM-1 have statistically significant prognostic relevance. PMID- 26368794 TI - Placental and Clinical Characteristics of Term Small-for-Gestational-Age Neonates: A Case-Control Study. AB - Numerous conditions, including placental vascular compromise, can lead to small for-gestational-age (SGA) infants. As few studies have investigated primarily term placentas from SGA infants, we compared placentas from 67 SGA infants to placentas from 67 infants with appropriate weights for gestational age (AGA) in this population, matched for gestational age and gender. Placental histology was reviewed and electronic records were queried for maternal and fetal birth data, infant morbidities, and infant follow-up weights. Comparison of these 2 cohorts showed that placentas from SGA infants were more likely to have smaller weights and thinner umbilical cords than those from AGA infants. SGA placentas had a significant increase in another uteroplacental malperfusion feature: single and multiple infarctions. Rates of preeclampsia, infant cardiac anomalies, and infant genetic abnormalities were not statistically different between groups. Fetal and maternal inflammatory responses, nongestational diabetes, and gestational hypertension were more common in the controls, but these are common indications for placental examination. No statistical differences were present for decidual vasculopathy, chronic villitis, intervillous thrombi, or meconium. More SGA neonates had hypoglycemia compared to their AGA counterparts. SGA infants tended to have decreased weights up to 7 months of age; however, the low number of infants with follow-up limited the statistical significance. This study confirms that small placental size and select features of uteroplacental malperfusion are more common in SGA versus AGA term placentas. The lack of other significant differences may be due to the inclusion of only term infants, with more severe pathology leading to preterm delivery. PMID- 26368795 TI - Management of Mild-to-Moderate Ulcerative Colitis. AB - Managing mild-to-moderate ulcerative colitis on the first view appears to be a simple task. However, real life often proofs the opposite and creates a challenging situation. In theory, mild-to-moderate disease should be sufficiently treated by mesalamine or alternatively by a probiotic. Insufficient treatment comprises the danger of leading to a flare, and hence, an exacerbation of the entire disease, with risk of progressing to severe disease. What are the considerations with regard to patient management in this situation? Certainly, disease distribution is the critical information, since it allows for planning the optimal route of administration, namely local versus systemic treatment. Novel pharmacological strategies might allow for reaching high local concentrations even at the left side of the colon or alternatively administer locally active budesonide throughout the entire colon frame, thus avoiding systemic side effects. Therapy planning has to involve the patient to identify how this can be included in daily life. Including the patient implies that depending on the condition, disease activity and even life quality, the individual therapy requires timely adaption. A recent study by Pedersen et al. [Inflamm Bowel Dis 2014;20:2276-2285] provides evidence that this strategy can be followed and leads to an overall better outcome. A last thought, besides the patient not taking the appropriate dose or lacking adherence to therapy, should consider that a worsening of disease could be due to infectious complications including Clostridium difficile or cytomegalovirus colitis. If all considerations fail within a reasonable time frame, therapy should be escalated. Patients in this situation often hesitate in accepting the need of immunosuppression. Future options, potentially including phosphatidylcholine, might bridge the gap between mesalamine, probiotics and immunosuppressive strategies. PMID- 26368796 TI - A green approach towards adoption of chemical reaction model on 2,5-dimethyl-2,5 di-(tert-butylperoxy)hexane decomposition by differential isoconversional kinetic analysis. AB - This study investigated the thermal degradation products of 2,5-dimethyl-2,5-di (tert-butylperoxy) hexane (DBPH), by TG/GC/MS to identify runaway reaction and thermal safety parameters. It also included the determination of time to maximum rate under adiabatic conditions (TMR(ad)) and self-accelerating decomposition temperature obtained through Advanced Kinetics and Technology Solutions. The apparent activation energy (Ea) was calculated from differential isoconversional kinetic analysis method using differential scanning calorimetry experiments. The Ea value obtained by Friedman analysis is in the range of 118.0-149.0 kJ mol(-1). The TMR(ad) was 24.0 h with an apparent onset temperature of 82.4 degrees C. This study has also established an efficient benchmark for a thermal hazard assessment of DBPH that can be applied to assure safer storage conditions. PMID- 26368797 TI - Porphyrin-functionalized porous polysulfone membrane towards an optical sensor membrane for sorption and detection of cadmium(II). AB - In this study, an optical sensor membrane was prepared for sorption and detection of cadmium(II) (Cd(II)) in aqueous solution. A polyanion, poly(sodium 4 styrenesulfonate) (PNaSS), was grafted onto the chloromethylated polysulfone (CMPSF) microporous membrane via surface-initiated ATRP. 5,10,15,20-tetrakis(4-N methylpyridyl) porphyrin p-toluenesulfonate (TMPyP) was immobilized onto the PNaSS-grafted polysulfone (PSF-PNaSS) membrane through electrostatic interaction. The TMPyP-functionalized membrane exhibited an enhanced sorption for, and distinct color and spectral response to cadmium(II) (Cd(II)) in aqueous solution. Larger immobilization capacity of TMPyP on the membrane led to stronger sorption for Cd(II), and smaller one made the optical sensor have a faster (in minutes) and more sensitive response to the ion. The detection limit study indicated that the functional membrane with proper amount of TMPyP (<0.5 mg/g) could still have color and spectral response to Cd(II) solutions at an extreme low concentration (10(-4) mg/L). The optical sensor membrane exhibited good stability and reusability which made it efficient for various sorptive removal and detection applications. PMID- 26368798 TI - Interactions between carbon nanodots with human serum albumin and gamma globulins: The effects on the transportation function. AB - Carbon nanodots (C-dots) have attracted great attention as a new class of luminescent nanomaterials due to their superior physical and chemical properties. In order to better understand the basic behavior of C-dots in biological systems, a series of photophysical measurements were applied to study the interactions of C-dots with human serum albumin (HSA) and gamma-globulins. The fluorescence of proteins was quenched by the dynamic mechanism rather than the formation of a protein/C-dots complex. The apparent dissociation constants of the C-dots bound to HSA and gamma-globulins were of the same order of magnitude. Furthermore, it is proven that C-dots showed little influence on the conformation of HSA and gamma-globulins. In addition, Fourier transform infrared and fluorescence spectroscopic studies demonstrated that the interaction between C-dots and two kinds of serum proteins was driven by hydrophobic and van der waals forces. Since the bioavailability of drugs can be modulated by their interactions with proteins, the variations of binding constants of three drugs with HSA and gamma globulins in the presence of different concentrations of C-dots (0-84 MUmol L( 1)) have also been analyzed in this work, to reflect the effect of C-dots on the transportation function of HSA and gamma-globulins. PMID- 26368799 TI - A study on metabolic prowess of Pseudomonas sp. RPT 52 to degrade imidacloprid, endosulfan and coragen. AB - A bacterial strain identified as Pseudomonas sp. RPT 52, was isolated from an agricultural field by soil enrichment technique. The bacterial strain was able to metabolize three different chlorinated pesticides; imidacloprid, endosulfan and coragen (belonging to neonicotinoid, organochlorine and anthranillic diamide categories, respectively). RPT 52 was able to degrade 46.5%, 96.6%, 92.7% and 80.16% of 0.5 mM of imidacloprid, endosulfan alpha, endosulfan beta and coragen, respectively, in minimal medium over a period of 40 h, when provided as sole source of carbon and energy. Degradation kinetics showed that imidacloprid, endosulfan alpha and endosulfan beta followed first order kinetics whereas coragen followed zero order kinetics. Toxicity studies show reduction in toxicity of the parent compound when degraded by RPT 52. Laboratory scale, soil microcosm studies showed that strain RPT 52 is a suitable candidate for bioremediation of endosulfan and coragen contaminated sites. Thus, RPT 52 holds potential for toxicity reduction in the affected environment. PMID- 26368800 TI - Adsorptive desulfurization and denitrogenation using metal-organic frameworks. AB - With the increasing worldwide demand for energy, utilization of fossil fuels is increasing proportionally. Additionally, new and unconventional energy sources are also being utilized at an increasing rate day-by-day. These sources, along with some industrial processes, result in the exposal of several sulfur- and nitrogen-containing compounds (SCCs and NCCs, respectively) to the environment, and the exposure is one of the greatest environmental threats in the recent years. Although, several methods were established for the removal of these pollutants during the last few decades, recent advancements in adsorptive desulfurization and denitrogenation (ADS and ADN, respectively) with metal organic frameworks (MOFs) make this the most promising and remarkable method. Therefore, many research groups are currently involved with ADS and ADN with MOFs, and the results are improving gradually by modifying the MOF adsorbents according to several specific adsorption mechanisms. In this review, ADS and ADN studies are thoroughly discussed for both liquid-phase and gas-phase adsorption. The MOF modification procedures, which are important for improved adsorption, are also described. To improve the knowledge among the scientific community, it is very important to understand the detailed chemistry and mechanism involved in a chemical process, which also creates the possibility and pathway for further developments in research and applications. Therefore, the mechanisms related to the adsorption procedures are also discussed in detail. From this review, it can be expected that the scientific community will obtain an understanding of the current state of ADS and ADN, their importance, and some encouragement and insight to take the research knowledge base to a higher level. PMID- 26368801 TI - Selective recovery of Ag(I) coordination anion from simulate nickel electrolyte using corn stalk based adsorbent modified by ammonia-thiosemicarbazide. AB - In nickel electrolyte, Ag(I) was present at trace level concentration (10-20 mg L(-1)) and existed in the form of AgCli(1-i) coordination anion, instead of Ag(+) positive ion usually in several sources. In the present study, TSC-NH3-OCS adsorbent based on natural corn stalk modified by ammonia (NH3)-thiosemicarbazide (TSC) was synthesized and characterized using some instrumental techniques. The TSC-NH3-OCS adsorbent could selectively adsorb Ag(I) as AgCl(i)(1-i) coordination anion from the Ag(I)-Cu(II)-Ni(II) simulate nickel electrolyte, especially in the case of the very high levels of Cu(II) and Ni(II), which significantly outperforms the commercial available resins. The adsorption mechanism was believed to be electrostatic interaction of the protonated bands of AgCl4(3-) with protonated thiol form of the thioamide units by FTIR and XPS analysis. The maximum adsorption capacity in the Ag(I) single and Ag(I)-Cu(II)-Ni(II) ternary system were obtained and calculated as 153.54 and 46.69 mg g(-1), respectively. The reasons that the maximum adsorption capacity of AgCl(i)(1-i) from the single and ternary system varied widely could be explained by adsorption kinetic and thermodynamic results. In addition, three successive sorption/desorption cycle runs from ternary system were performed which indicated that the TSC-NH3-OCS adsorbent has a good performance for recovery Ag(I) from simulate nickel electrolyte. PMID- 26368802 TI - Mechanism of Co(II) adsorption by zero valent iron/graphene nanocomposite. AB - Nanoscale zero valent iron (ZVI)/graphene (GF) composite was prepared and characterized by Brunauer-Emmett-Teller (BET) surface area measurement and zeta potential determination. The adsorption isotherm of Co(II) in aqueous solution, as well as the influence of pH values and ionic strengths was studied. The mechanism of Co(II) adsorption by GF was investigated through analyzing the sorption products at initial pH of 3.0, 6.0 and 9.0 using high-resolution transmission electron microscope with energy dispersive X-ray detector (HRTEM EDX), X-ray diffraction (XRD), vibrating-sample magnetometer (VSM), Raman spectra, X-ray photoelectron spectroscopy (XPS) and X-ray absorption fine structure (XAFS) measurement. The results indicated that Langmuir isotherm model fitted well and the adsorption capacity was 131.58 mg g(-1) at 30 degrees C. Adsorption capacity was not significantly influenced by ionic strength and kept high at pH 4.0~9.0. The detail information of GF-Co interaction at different initial pH values was obtained using XAFS analysis combined with other characterization methods. Coordination numbers (CN) and interatomic distances (R) of both Fe and Co were given. At pH 3.0 and pH 6.0, the Co-substituted iron oxides transformed to CoFe2O4-like structure, while at pH 9.0 they changed to green rust-like phases. Co occupied preferentially in the octahedral sites in acid solution. The adsorption mechanism of Co(II) was attributed to inner-sphere complexation and dissolution/re-precipitation of the substituted metal oxides. PMID- 26368803 TI - Exercise Prevents Memory Impairment Induced by Arsenic Exposure in Mice: Implication of Hippocampal BDNF and CREB. AB - High concentrations of arsenic, which can be occasionally found in drinking water, have been recognized as a global health problem. Exposure to arsenic can disrupt spatial memory; however, the underlying mechanism remains unclear. In the present study, we tested whether exercise could interfere with the effect of arsenic exposure on the long-term memory (LTM) of object recognition in mice. Arsenic (0, 1, 3, and 10 mg/ kg, i.g.) was administered daily for 12 weeks. We found that arsenic at dosages of 1, 3, and 10 mg/kg decreased body weight and increased the arsenic content in the brain. The object recognition LTM (tested 24 h after training) was disrupted by 3 mg/ kg and 10 mg/ kg, but not 1 mg/ kg arsenic exposure. Swimming exercise also prevented LTM impairment induced by 3 mg/ kg, but not with 10 mg/ kg, of arsenic exposure. The expression of brain derived neurotrophic factor (BDNF) and phosphorylated cAMP-response element binding protein (pCREB) in the CA1 and dentate gyrus areas (DG) of the dorsal hippocampus were decreased by 3 mg/ kg and 10 mg/ kg, but not by 1 mg/ kg, of arsenic exposure. The decrease in BDNF and pCREB in the CA1 and DG induced by 3 mg/ kg, but not 10 mg/ kg, of arsenic exposure were prevented by swimming exercise. Arsenic exposure did not affect the total CREB expression in the CA1 or DG. Taken together, these results indicated that swimming exercise prevented the impairment of object recognition LTM induced by arsenic exposure, which may be mediated by BDNF and CREB in the dorsal hippocampus. PMID- 26368805 TI - Long-Term Field Study Reveals Subtle Effects of the Invasive Alga Sargassum muticum upon the Epibiota of Zostera marina. AB - Invasive species can alter coastal ecosystems both directly, e.g. through competition for substratum and nutrients, and indirectly. Indirect effects may be mediated by creation of dissimilar or inimical habitats, changes in predator and/or prey assemblages, alterations in associated biota, and perturbations of water movement and thermal regimes. Previous studies have shown that invasive algae can modify native habitat architecture, disrupt intricately linked food webs and alter epibiotic assemblages. In the UK, the seagrass Zostera marina supports a diverse epibiotic assemblage, influencing key factors such as sediment dynamics, depositional regime and trophic linkages. Increasing encroachment of the invasive alga Sargassum muticum into seagrass meadows changes the physical and chemical characteristics of the local environment and creates the potential for changes in the epibionts associated with the seagrass blades, threatening the integrity of the seagrass ecosystem. We investigated the effects of S. muticum invasion upon the epibiota of Z. marina in a drowned river valley in SW England seasonally from spring to autumn over four years in an in-situ manipulative experiment, comparing permanent quadrats with and without artificially introduced S. muticum. Epibiota were weighed, identified to the most detailed operational taxonomic unit (OTU) possible, and unitary organisms were enumerated. Multivariate PERMANOVA+ analysis revealed significant differences in epibiont assemblages between Sargassum treatments. Linear mixed effects models indicated that differences in epibiota assemblage composition were not reflected as significant differences in mean biomass per sample, or number of epibiont OTUs per sample. We conclude that S. muticum invasion into Z. marina meadows may significantly alter the species composition and abundance distribution of epibiotic assemblages found on the blades of the seagrass. Thus S. muticum invasion could have more wide-reaching effects on processes within coastal ecosystems than predicted purely by direct effects. PMID- 26368804 TI - Transcriptome Analysis of the Central and Peripheral Nervous Systems of the Spider Cupiennius salei Reveals Multiple Putative Cys-Loop Ligand Gated Ion Channel Subunits and an Acetylcholine Binding Protein. AB - Invertebrates possess a diverse collection of pentameric Cys-loop ligand gated ion channel (LGIC) receptors whose molecular structures, evolution and relationships to mammalian counterparts have been intensely investigated in several clinically and agriculturally important species. These receptors are targets for a variety of control agents that may also harm beneficial species. However, little is known about Cys-loop receptors in spiders, which are important natural predators of insects. We assembled de novo transcriptomes from the central and peripheral nervous systems of the Central American wandering spider Cupiennius salei, a model species for neurophysiological, behavioral and developmental studies. We found 15 Cys-loop receptor subunits that are expected to form anion or cation permeable channels, plus a putative acetylcholine binding protein (AChBP) that has only previously been reported in molluscs and one annelid. We used phylogenetic and sequence analysis to compare the spider subunits to homologous receptors in other species and predicted the 3D structures of each protein using the I-Tasser server. The quality of homology models improved with increasing sequence identity to the available high-resolution templates. We found that C. salei has orthologous gamma-aminobutyric acid (GABA), GluCl, pHCl, HisCl and nAChalpha LGIC subunits to other arthropods, but some subgroups are specific to arachnids, or only to spiders. C. salei sequences were phylogenetically closest to gene fragments from the social spider, Stegodyphus mimosarum, indicating high conservation within the Araneomorphae suborder of spiders. C. salei sequences had similar ligand binding and transmembrane regions to other invertebrate and vertebrate LGICs. They also had motifs associated with high sensitivity to insecticides and antiparasitic agents such as fipronil, dieldrin and ivermectin. Development of truly selective control agents for pest species will require information about the molecular structure and pharmacology of Cys-loop receptors in beneficial species. PMID- 26368806 TI - The Efficacy of the BCG Vaccine against Newly Emerging Clinical Strains of Mycobacterium tuberculosis. AB - To date, most new vaccines against Mycobacterium tuberculosis, including new recombinant versions of the current BCG vaccine, have usually been screened against the laboratory strains H37Rv or Erdman. In this study we took advantage of our recent work in characterizing an increasingly large panel of newly emerging clinical isolates [from the United States or from the Western Cape region of South Africa], to determine to what extent vaccines would protect against these [mostly high virulence] strains. We show here that both BCG Pasteur and recombinant BCG Aeras-422 [used here as a good example of the new generation BCG vaccines] protected well in both mouse and guinea pig low dose aerosol infection models against the majority of clinical isolates tested. However, Aeras 422 was not effective in a long term survival assay compared to BCG Pasteur. Protection was very strongly expressed against all of the Western Cape strains tested, reinforcing our viewpoint that any attempt at boosting BCG would be very difficult to achieve statistically. This observation is discussed in the context of the growing argument made by others that the failure of a recent vaccine trial disqualifies the further use of animal models to predict vaccine efficacy. This viewpoint is in our opinion completely erroneous, and that it is the fitness of prevalent strains in the trial site area that is the centrally important factor, an issue that is not being addressed by the field. PMID- 26368808 TI - Influence of Environmental Factors, Cultural Practices, and Herbicide Application on Seed Germination and Emergence Ecology of Ischaemum rugosum Salisb. AB - Ischaemum rugosum Salisb. (Saramolla grass) is a noxious weed of rice that is difficult to control by chemical or mechanical means once established. A study was conducted to determine the effect of light, temperature, salt, drought, flooding, rice residue mulch, burial depth, and pre-emergence herbicides on seed germination and emergence of I. rugosum. Germination was stimulated by light and inhibited under complete darkness. Optimum temperature for germination was 30/20 degrees C (97.5% germination). Germination reduced from 31 to 3.5% when the osmotic potential of the growing medium decreased from -0.1 to -0.6 MPa and no germination occurred at -0.8 MPa. Germination was 18 and 0.5% at 50 and 100 mM NaCl concentrations, respectively, but was completely inhibited at 150 mM or higher. Residue application at 1-6 t ha-1 reduced weed emergence by 35-88% and shoot biomass by 55-95%. The efficacy of pre-emergence herbicides increased with increasing application rates and decreased with increasing rice residue mulching. The efficacy of herbicides was in the order of oxadiazon> pendimethalin> pretilachlor. At 6 t ha-1, all herbicides, regardless of rates, did not differ from the control treatment. I. rugosum seeds buried at 2 cm or deeper did not emerge; however, they emerged by 4.5 and 0.5% at 0.5 and 1 cm depths, respectively, compared to the 39% germination for soil surface seeding. Flooding at 4 DAS or earlier reduced seedling emergence and shoot biomass while flooding at 8 DAS reduced only seedling emergence. The depth and timing of flooding independently reduced root biomass. Flooding at 4 and 6 cm depths reduced the root biomass. Relative to flooding on the day of sowing, flooding at 8 DAS increased root biomass by 89%. Similarly, flooding on the day of sowing and at 2 DAS reduced the root-shoot biomass ratio. Under the no-flood treatment, increasing rates of pretilachlor from 0.075 to 0.3 kg ai ha-1 reduced weed emergence by 61-79%. At the flooding depth of 2-4 cm, pretilachlor reduced weed emergence and shoot and root biomass, but the differences across rates were non significant. Information generated in this study will be helpful in developing integrated weed management strategies for managing this weed. PMID- 26368807 TI - Impact-Free Measurement of Microtubule Rotations on Kinesin and Cytoplasmic Dynein Coated Surfaces. AB - Knowledge about the three-dimensional stepping of motor proteins on the surface of microtubules (MTs) as well as the torsional components in their power strokes can be inferred from longitudinal MT rotations in gliding motility assays. In previous studies, optical detection of these rotations relied on the tracking of rather large optical probes present on the outer MT surface. However, these probes may act as obstacles for motor stepping and may prevent the unhindered rotation of the gliding MTs. To overcome these limitations, we devised a novel, impact-free method to detect MT rotations based on fluorescent speckles within the MT structure in combination with fluorescence-interference contrast microscopy. We (i) confirmed the rotational pitches of MTs gliding on surfaces coated by kinesin-1 and kinesin-8 motors, (ii) demonstrated the superiority of our method over previous approaches on kinesin-8 coated surfaces at low ATP concentration, and (iii) identified MT rotations driven by mammalian cytoplasmic dynein, indicating that during collective motion cytoplasmic dynein side-steps with a bias in one direction. Our novel method is easy to implement on any state of-the-art fluorescence microscope and allows for high-throughput experiments. PMID- 26368810 TI - A Rescue Strategy for Handling Unevaluable Patients in Simon's Two Stage Design. AB - For phase II oncology trials, Simon's two-stage design is the most commonly used strategy. However, when clinically unevaluable patients occur, the total number of patients included at each stage differs from what was initially planned. Such situations raise concerns about the operating characteristics of the trial design. This paper evaluates three classical ad hoc strategies and a novel one proposed in this work for handling unevaluable patients. This latter is called the rescue strategy which adapts the critical stopping rules to the number of unevaluable patients at each stage without modifying the planned sample size. blue Simulations show that none of these strategies perfectly match the original target constraints for type I and II error rates. Our rescue strategy is nevertheless the one which best approaches the target error rates requirement. A re-analysis of one real phase II clinical trials on metastatic cancer illustrates the use of the proposed strategy. PMID- 26368809 TI - Quinolinic Acid Responses during Interferon-alpha-Induced Depressive Symptomatology in Patients with Chronic Hepatitis C Infection - A Novel Aspect for Depression and Inflammatory Hypothesis. AB - BACKGROUND: The aim of this exploratory study is to gain for the first time a more comprehensive picture of the impact of changes of quinolinic acid concentrations on depressive symptomatology during and after IFN-alpha therapy. METHODS: The quinolinic acid concentrations of 35 HCV patients are examined in a prospective survey over the entire period of IFN-alpha treatment as well as three months later at six different times (baseline, one, three, six and nine months after the beginning of IFN-alpha treatment, and after the end of treatment). RESULTS: During IFN-alpha treatment Hamilton Depression Rating Scale scores rise significantly. At the same time there is greater activity of indoleamine 2,3 dioxygenase, with a resulting increase in plasma kynurenine concentrations. Compared to baseline values quinolinic acid concentrations increase significantly during therapy, reflecting an increased neurotoxic challenge. In addition, patients with higher scores in the Hamilton Depression Rating Scale at six and nine months after starting therapy show significantly higher levels of quinolinic acid concentration. CONCLUSIONS: The increase of quinolinic acid during IFN-alpha therapy might contribute to depressive symptomatology through the neurotoxic challenge caused by quinolinic acid. Subsequently, our exploratory study results support the inflammatory hypothesis of depression. The awareness of relevant risk factors of IFN-alpha treatment-induced depression is essential to develop preventative treatment strategies. PMID- 26368811 TI - Correction: R54C Mutation of NOTCH3 Gene in the First Rungus Family with CADASIL. PMID- 26368812 TI - Distribution of GNAQ and GNA11 Mutation Signatures in Uveal Melanoma Points to a Light Dependent Mutation Mechanism. AB - Uveal melanomas (UM) originate from melanocytes in the interior wall of the eye, namely from the iris, ciliary body and the choroid with marked differences in light exposure (from dark anterior to illuminated posterior). In contrast to UV radiation, focused or converging visible light readily reaches the retina and can damage DNA which possibly contributes to UM development. In this report choroidal, ciliochoroidal and iridociliary melanomas were analyzed for GNAQ and GNA11 mutations which were subsequently correlated to the location of tumor origin. Hotspot mutations in GNAQ and GNA11 can be divided in A>T and in A>C mutation signatures. The GNAQ A626C mutation (Q209P) was almost exclusively observed in choroidal melanomas from the illuminated posterior side. On the other hand, ciliochoroidal UM from the dark anterior side with mostly A>T mutations were clearly associated with light-colored eyes. Combined these data suggest a light and a pigment dependent etiology in UM development. PMID- 26368814 TI - Correction: Pathogen-Specific T Cell Polyfunctionality Is a Correlate of T Cell Efficacy and Immune Protection. PMID- 26368813 TI - Evaluating Clinical Practice Guidelines Based on Their Association with Return to Work in Administrative Claims Data. AB - OBJECTIVE: To examine the association between non-adherence to clinical practice guidelines (CPGs) and time to return to work (RTW) for patients with workplace injuries. DATA SOURCES/STUDY SETTING: Secondary analysis of medical billing and disability data for 148,199 for shoulder and back injuries from a workers' compensation insurer. STUDY DESIGN: Cox proportional hazard regression is used to estimate the association between time to RTW and receipt of guideline-discordant care. We test the robustness of our findings to an omitted confounding variable. DATA COLLECTION: Collected by the insurer from the time an injury was reported, through recovery or last follow-up. PRINCIPAL FINDINGS: Receiving guideline discordant care was associated with slower RTW for only some guidelines. Early receipt of care, and getting less than the recommended amount of care, were correlated with faster RTW. Excessive physical therapy, bracing, and injections were associated with slower RTW. CONCLUSIONS: There is not a consistent relationship between performance on CPGs and RTW. The association between performance on CPG and RTW is difficult to measure in observational data, because analysts cannot control for omitted variables that affect a patient's treatment and outcomes. CPGs supported by observational studies or randomized trials may have a more certain relationship to health outcomes. PMID- 26368815 TI - Chronic Lead Exposure and Mixed Factors of Gender*Age*Brain Regions Interactions on Dendrite Growth, Spine Maturity and NDR Kinase. AB - NDR1/2 kinase is essential in dendrite morphology and spine formation, which is regulated by cellular Ca2+. Lead (Pb) is a potent blocker of L-type calcium channel and our recent work showed Pb exposure impairs dendritic spine outgrowth in hippocampal neurons in rats. But the sensitivity of Pb-induced spine maturity with mixed factors (gender*age*brain regions) remains unknown. This study aimed to systematically investigate the effect of Pb exposure on spine maturity in rat brain with three factors (gender*age*brain regions), as well as the NDR1/2 kinase expression. Sprague-Dawley rats were exposed to Pb from parturition to postnatal day 30, 60, 90, respectively. Golgi-Cox staining was used to examine spine maturity. Western blot assay was applied to measure protein expression and real time fluorescence quantitative PCR assay was used to examine mRNA levels. The results showed chronic Pb exposure significantly decreased dendritic length and impaired spine maturity in both rat hippocampus and medial prefrontal cortex. The impairment of dendritic length induced by Pb exposure tended to adolescence > adulthood, hippocampus > medial prefrontal cortex and female > male. Pb exposure induced significant damage in spine maturity during adolescence and early adult while little damage during adult in male rat brain and female medial prefrontal cortex. Besides, there was sustained impairment from adolescence to adulthood in female hippocampus. Interestingly, impairment of spine maturity followed by Pb exposure was correlated with NDR1/2 kinase. The reduction of NDR1/2 kinase protein expression after Pb exposure was similar to the result of spine maturity. In addition, NDR2 and their substrate Rabin3 mRNA levels were significantly decreased by Pb exposure in developmental rat brain. Taken together, Pb exposure impaired dendrite growth and maturity which was subject to gender*age*brain regions effects and related to NDR1/2 signal expression. PMID- 26368817 TI - Mutation screening of the ubiquitin ligase gene RNF135 in French patients with autism. AB - Many genes are now thought to confer susceptibility to autism. Despite the fact that this neuropsychiatric disease appears to be related to several different causes, common cellular and molecular pathways have emerged and point to synaptic dysfunction or cellular growth. Several studies have indicated the importance of the ubiquitin pathway in synaptic function and the aetiology of autism. Here, we focused on the ring finger protein 135 (RNF135) gene, encoding an E3 ubiquitin ligase expressed in the cortex and cerebellum, and located in the NF1 gene locus in 17q11.2, a region linked to autism. We carried out a genetic analysis of the coding sequence of RFN135 in a French cohort of patients with autism and observed a significantly increased frequency of genotypes carrying the rare allele of the rs111902263 (p.R115K) missense variant in patients (P=0.0019, odds ratio: 4.23, 95% confidence interval: 1.87-9.57). Particularly, three unrelated patients showed a homozygous genotype for K115, a situation not observed in the 1812 control individuals. Further cellular and molecular studies are required to elucidate the role of this gene and the variant K115 in brain development and neuronal function. PMID- 26368816 TI - Treatment with a Small Molecule Mutant IDH1 Inhibitor Suppresses Tumorigenic Activity and Decreases Production of the Oncometabolite 2-Hydroxyglutarate in Human Chondrosarcoma Cells. AB - Chondrosarcomas are malignant bone tumors that produce cartilaginous matrix. Mutations in isocitrate dehydrogenase enzymes (IDH1/2) were recently described in several cancers including chondrosarcomas. The IDH1 inhibitor AGI-5198 abrogates the ability of mutant IDH1 to produce the oncometabolite D-2 hydroxyglutarate (D 2HG) in gliomas. We sought to determine if treatment with AGI-5198 would similarly inhibit tumorigenic activity and D-2HG production in IDH1-mutant human chondrosarcoma cells. Two human chondrosarcoma cell lines, JJ012 and HT1080 with endogenous IDH1 mutations and a human chondrocyte cell line C28 with wild type IDH1 were employed in our study. Mutation analysis of IDH was performed by PCR based DNA sequencing, and D-2HG was detected using tandem mass spectrometry. We confirmed that JJ012 and HT1080 harbor IDH1 R132G and R132C mutation, respectively, while C28 has no mutation. D-2HG was detectable in cell pellets and media of JJ012 and HT1080 cells, as well as plasma and urine from an IDH-mutant chondrosarcoma patient, which decreased after tumor resection. AGI-5198 treatment decreased D-2HG levels in JJ012 and HT1080 cells in a dose-dependent manner, and dramatically inhibited colony formation and migration, interrupted cell cycling, and induced apoptosis. In conclusion, our study demonstrates anti-tumor activity of a mutant IDH1 inhibitor in human chondrosarcoma cell lines, and suggests that D-2HG is a potential biomarker for IDH mutations in chondrosarcoma cells. Thus, clinical trials of mutant IDH inhibitors are warranted for patients with IDH mutant chondrosarcomas. PMID- 26368818 TI - Phenotypic heterogeneity in study populations may significantly confound the results of genetic association studies on alcohol dependence. AB - BACKGROUND: The interpretation of genetic studies on alcohol dependence may be confounded by the co-occurrence of substance dependence, psychiatric disorders and alcohol-related comorbidities, for example, cirrhosis. Significant single marker and haplotypic associations between polymorphisms in the zinc finger gene, ZNF699, and alcohol dependence were reported in the Irish Affected Sib Pair Study of Alcohol Dependence population, one-third of whom had co-occurring substance dependence while 80% had identified psychiatric comorbidity. The aim of this study was to explore variant ZNF699 associations with alcohol dependence while exercising controls for potential confounders. METHODS: The study population was comprised of 1449 alcohol-dependent cases and 1283 population controls; all were of British or Irish ancestry. None of the cases had a history of dependence on other substances, and the frequency of comorbid depression was low. A separate, ancestry-matched cohort of 196 opioid-dependent cases was also included. Genotyping for the four previously identified SNPs of interest in ZNF699 was performed using K-Biosciences Competitive Allele Specific PCR. RESULTS: No single marker associations were found between polymorphisms in ZNF699 and alcohol dependence per se. A significant allelic association was found between rs7254880 in ZNF699 and alcohol-related cirrhosis (n=292), using cases with no biopsy evidence of liver disease (n=314) as controls (P=0.013). Significant allelic associations were also found between rs12460279 (P=0.028), rs7252865 (P=0.012) and rs10854142 (P=0.016) in ZNF699 and opioid dependence. CONCLUSION: Phenotypic variation in study populations may contribute towards the nonreplication of genetic association studies on alcohol dependence; controls for recognised confounding variables should be exercised whenever possible. PMID- 26368820 TI - Efficient Activation of Pathogenic DeltaPhe501 Mutation in Monocarboxylate Transporter 8 by Chemical and Pharmacological Chaperones. AB - Monocarboxylate transporter 8 (MCT8) is a thyroid hormone transmembrane transporter expressed in many cell types, including neurons. Mutations that inactivate transport activity of MCT8 cause severe X-linked psychomotor retardation in male patients, a syndrome originally described as the Allan Herndon-Dudley syndrome. Treatment options currently explored the focus on finding thyroid hormone-like compounds that bypass MCT8 and enter cells through different transporters. Because MCT8 is a multipass transmembrane protein, some pathogenic mutations affect membrane trafficking while potentially retaining some transporter activity. We explore here the effects of chemical and pharmacological chaperones on the expression and transport activity of the MCT8 mutant DeltaPhe501. Dimethylsulfoxide, 4-phenylbutyric acid as well as its sodium salt, and the isoflavone genistein increase T3 uptake into MDCK1 cells stably transfected with mutant MCT8-DeltaPhe501. We show that DeltaPhe501 represents a temperature-sensitive mutant protein that is stabilized by the proteasome inhibitor MG132. 4-Phenylbutyrate has been used to stabilize DeltaPhe508 mutant cystic fibrosis transmembrane conductance regulator protein and is in clinical use in patients with urea cycle defects. Genistein is enriched in soy and available as a nutritional supplement. It is effective in stabilizing MCT8 DeltaPhe501 at 100 nM concentration. Expression of the L471P mutant is increased in response to phenylbutyrate, but T3 uptake activity is not induced, supporting the notion that the chaperone specifically increases membrane expression. Our findings suggest that certain pathogenic MCT8 mutants may be responsive to (co )treatment with readily available compounds, which increase endogenous protein function. PMID- 26368819 TI - Mapping the Risk of Soil-Transmitted Helminthic Infections in the Philippines. AB - BACKGROUND: In order to increase the efficient allocation of soil-transmitted helminth (STH) disease control resources in the Philippines, we aimed to describe for the first time the spatial variation in the prevalence of A. lumbricoides, T. trichiura and hookworm across the country, quantify the association between the physical environment and spatial variation of STH infection and develop predictive risk maps for each infection. METHODOLOGY/PRINCIPAL FINDINGS: Data on STH infection from 35,573 individuals across the country were geolocated at the barangay level and included in the analysis. The analysis was stratified geographically in two major regions: 1) Luzon and the Visayas and 2) Mindanao. Bayesian geostatistical models of STH prevalence were developed, including age and sex of individuals and environmental variables (rainfall, land surface temperature and distance to inland water bodies) as predictors, and diagnostic uncertainty was incorporated. The role of environmental variables was different between regions of the Philippines. This analysis revealed that while A. lumbricoides and T. trichiura infections were widespread and highly endemic, hookworm infections were more circumscribed to smaller foci in the Visayas and Mindanao. CONCLUSIONS/SIGNIFICANCE: This analysis revealed significant spatial variation in STH infection prevalence within provinces of the Philippines. This suggests that a spatially targeted approach to STH interventions, including mass drug administration, is warranted. When financially possible, additional STH surveys should be prioritized to high-risk areas identified by our study in Luzon. PMID- 26368821 TI - Safe Corridor to Access Clivus for Endoscopic Trans-Sphenoidal Surgery: A Radiological and Anatomical Study. AB - PURPOSE: Penetration of the clivus is required for surgical access of the brain stem. The endoscopic transclivus approach is a difficult procedure with high risk of injury to important neurovascular structures. We undertook a novel anatomical and radiological investigation to understand the structure of the clivus and neurovascular structures relevant to the extended trans-nasal trans-sphenoid procedure and determine a safe corridor for the penetration of the clivus. METHOD: We examined the clivus region in the computed tomographic angiography (CTA) images of 220 adults, magnetic resonance (MR) images of 50 adults, and dry skull specimens of 10 adults. Multiplanar reconstruction (MPR) of the CT images was performed, and the anatomical features of the clivus were studied in the coronal, sagittal, and axial planes. The data from the images were used to determine the anatomical parameters of the clivus and neurovascular structures, such as the internal carotid artery and inferior petrosal sinus. RESULTS: The examination of the CTA and MR images of the enrolled subjects revealed that the thickness of the clivus helped determine the depth of the penetration, while the distance from the sagittal midline to the important neurovascular structures determined the width of the penetration. Further, data from the CTA and MR images were consistent with those retrieved from the examination of the cadaveric specimens. CONCLUSION: Our findings provided certain pointers that may be useful in guiding the surgery such that inadvertent injury to vital structures is avoided and also provided supportive information for the choice of the appropriate endoscopic equipment. PMID- 26368823 TI - Epidemiology of invasive pneumococcal disease in Saudi Arabian children younger than 5years of age. AB - This study evaluated the incidence, serotype distribution, and antimicrobial susceptibility of invasive pneumococcal disease (IPD) in Saudi Arabian children. This multicenter, prospective, clinical surveillance study included children under 5years of age, residents of one of the seven study health areas, who were brought to a study hospital with suspicion of IPD. Bacterial isolates from sterile site samples, collected less than 24h after hospital visit/admission, were identified, serotyped, and tested for antibiotic susceptibility. Between June 2007 and January 2009, 631 episodes of suspected IPD were recorded, and 623 were included in the analysis. One child (0.2%) had previously received one dose of a pneumococcal vaccine. Forty-seven episodes were positive for Streptococcus pneumoniae and three for Haemophilus influenzae. The incidence of confirmed IPD cases was estimated to be 2.5-21.6 per 100,000 children (<5years). Among the 46 S. pneumoniae isolates serotyped and tested for antibiotic susceptibility, the most common serotypes were 5 and 23F (20% each), 6B (17%), and 1 and 14 (11% each). Sixty-three percent of isolates were multidrug-resistant. Vaccination of Saudi Arabian children with expanded-coverage conjugate pneumococcal vaccines containing serotypes 1 and 5 could have a substantial impact to prevent IPD in this population. PMID- 26368822 TI - Identification of Tetraazacyclic Compounds as Novel Potent Inhibitors Antagonizing RORgammat Activity and Suppressing Th17 Cell Differentiation. AB - CD4+ T-helper cells that produce interleukin-17 (Th17 cells) are characterized as pathological T-helper cells in autoimmune diseases. Differentiation of human and mouse Th17 cells requires a key transcription regulator, retinoic acid receptor related orphan receptor gammat (RORgammat), which is a potential therapeutic target for autoimmune diseases. To develop a therapeutic agent for Th17-mediated autoimmune diseases, we have established a high-throughput screening (HTS) assay for candidate screening, in which the luciferase activity in RORgammat-LBD positive and negative Jurkat cells were analyzed to evaluate induction of RORgammat activity by compounds. This technique was applied to screen a commercially-available drug-like chemical compound library (Enamine) which contains 20155 compounds. The screening identified 17 compounds that can inhibit RORgammat function in the HTS screen system. Of these, three tetraazacyclic compounds can potently inhibit RORgammat activity, and suppress Th17 differentiation and IL-17 production. These three candidate compounds could significantly attenuate the expression of the Il17a by 65%- 90%, and inhibit IL 17A secretion by 47%, 63%, and 74%, respectively. These compounds also exhibited a potent anti-RORgammat activity, with EC50 values of 0.25 MUM, 0.67 MUM and 2.6 MUM, respectively. Our data demonstrated the feasibility of targeting the RORgammat to inhibit Th17 cell differentiation and function with these tetraazacyclic compounds, and the potential to improve the structure of these compounds for autoimmune diseases therapeutics. PMID- 26368824 TI - Continued Follow-Up of Phambili Phase 2b Randomized HIV-1 Vaccine Trial Participants Supports Increased HIV-1 Acquisition among Vaccinated Men. AB - BACKGROUND: The Phase 2b double-blinded, randomized Phambili/HVTN 503 trial evaluated safety and efficacy of the MRK Ad5 gag/pol/nef subtype B HIV-1 preventive vaccine vs placebo in sexually active HIV-1 seronegative participants in South Africa. Enrollment and vaccinations stopped and participants were unblinded but continued follow-up when the Step study evaluating the same vaccine in the Americas, Caribbean, and Australia was unblinded for non-efficacy. Final Phambili analyses found more HIV-1 infections amongst vaccine than placebo recipients, impelling the HVTN 503-S recall study. METHODS: HVTN 503-S sought to enroll all 695 HIV-1 uninfected Phambili participants, provide HIV testing, risk reduction counseling, physical examination, risk behavior assessment and treatment assignment recall. After adding HVTN 503-S data, HIV-1 infection hazard ratios (HR vaccine vs. placebo) were estimated by Cox models. RESULTS: Of the 695 eligible, 465 (67%) enrolled with 230 from the vaccine group and 235 from the placebo group. 38% of the 184 Phambili dropouts were enrolled. Enrollment did not differ by treatment group, gender, or baseline HSV-2. With the additional 1286 person years of 503-S follow-up, the estimated HR over Phambili and HVTN 503-S follow-up was 1.52 (95% CI 1.08-2.15, p = 0.02, 82 vaccine/54 placebo infections). The HR was significant for men (HR = 2.75, 95% CI 1.49, 5.06, p = 0.001) but not for women (HR = 1.12, 95% CI 0.73, 1.72, p = 0.62). CONCLUSION: The additional follow-up from HVTN 503-S supported the Phambili finding of increased HIV-1 acquisition among vaccinated men and strengthened the evidence of lack of vaccine effect among women. TRIAL REGISTRATION: clinicaltrials.gov NCT00413725 SA National Health Research Database DOH-27-0207-1539. PMID- 26368826 TI - Zn(OTf)2 promoted rearrangement of 1,2-cyclopropanated sugars with amines: a convenient method for the synthesis of 3-polyhydroxyalkyl-substituted pyrrole derivatives. AB - A rearrangement reaction of 1,2-cyclopropanated sugars with alkylamines or arylamines promoted by Zn(OTf)2 is described. The method offers a series of 3 polyhydroxyalkyl-substituted pyrrole derivatives with multiple chiral centers in moderate to excellent yields. The epimerization is achieved by inverting the stereochemistry at the free hydroxyl group of the resulting pyrrole, which would give access to many more possible stereoisomers. PMID- 26368825 TI - Retinoic Acid Activity in Undifferentiated Neural Progenitors Is Sufficient to Fulfill Its Role in Restricting Fgf8 Expression for Somitogenesis. AB - Bipotent axial stem cells residing in the caudal epiblast during late gastrulation generate neuroectodermal and presomitic mesodermal progeny that coordinate somitogenesis with neural tube formation, but the mechanism that controls these two fates is not fully understood. Retinoic acid (RA) restricts the anterior extent of caudal fibroblast growth factor 8 (Fgf8) expression in both mesoderm and neural plate to control somitogenesis and neurogenesis, however it remains unclear where RA acts to control the spatial expression of caudal Fgf8. Here, we found that mouse Raldh2-/- embryos, lacking RA synthesis and displaying a consistent small somite defect, exhibited abnormal expression of key markers of axial stem cell progeny, with decreased Sox2+ and Sox1+ neuroectodermal progeny and increased Tbx6+ presomitic mesodermal progeny. The Raldh2-/- small somite defect was rescued by treatment with an FGF receptor antagonist. Rdh10 mutants, with a less severe RA synthesis defect, were found to exhibit a small somite defect and anterior expansion of caudal Fgf8 expression only for somites 1-6, with normal somite size and Fgf8 expression thereafter. Rdh10 mutants were found to lack RA activity during the early phase when somites are small, but at the 6-somite stage RA activity was detected in neural plate although not in presomitic mesoderm. Expression of a dominant-negative RA receptor in mesoderm eliminated RA activity in presomitic mesoderm but did not affect somitogenesis. Thus, RA activity in the neural plate is sufficient to prevent anterior expansion of caudal Fgf8 expression associated with a small somite defect. Our studies provide evidence that RA restriction of Fgf8 expression in undifferentiated neural progenitors stimulates neurogenesis while also restricting the anterior extent of the mesodermal Fgf8 mRNA gradient that controls somite size, providing new insight into the mechanism that coordinates somitogenesis with neurogenesis. PMID- 26368828 TI - An Iron-based Film for Highly Efficient Electrocatalytic Oxygen Evolution from Neutral Aqueous Solution. AB - An ultrathin Fe-based film was prepared by electrodeposition from an Fe(II) solution through a fast and simple cyclic voltammetry method. The extremely low Fe loading of 12.3 nmol cm(-2) on indium tin oxide electrodes is crucial for high atom efficiency and transparence of the resulted film. This Fe-based film was shown to be a very efficient electrocatalyst for oxygen evolution from neutral aqueous solution with remarkable activity and stability. In a 34 h controlled potential electrolysis at 1.45 V (vs NHE) and pH 7.0, impressive turnover number of 5.2 * 10(4) and turnover frequency of 1528 h(-1) were obtained. To the best of our knowledge, these values represent one of the highest among electrodeposited catalyst films for water oxidation under comparable conditions. The morphology and the composition of the catalyst film was determined by scanning electron microscopy, transmission electron microscopy, energy-dispersive X-ray, and X-ray photoelectron spectroscopy, which all confirmed the deposition of Fe-based materials with Fe(III) oxidation state on the electrode. This study is significant because of the use of iron, the fast and simple cyclic voltammetry electrodeposition, the extremely low catalyst loading and thus the transparency of the catalyst film, the remarkable activity and stability, and the oxygen evolution in neutral aqueous media. PMID- 26368827 TI - Using Serum Advanced Glycation End Products-Peptides to Improve the Efficacy of World Health Organization Fasting Plasma Glucose Criterion in Screening for Diabetes in High-Risk Chinese Subjects. AB - The efficacy of using fasting plasma glucose (FPG) alone as a preferred screening test for diabetes has been questioned. This study was aimed to evaluate whether the use of serum advanced glycation end products-peptides (sAGEP) would help to improve the efficacy of FPG in diabetes screening among high-risk Chinese subjects with FPG <7.0 mmol/L. FPG, 2-h plasma glucose (2h-PG), serum glycated haemoglobin A1c (HbA1c), and sAGEP were measured in 857 Chinese subjects with risk factors for diabetes. The areas under receiver operating characteristic (ROC) curves generated by logistic regression models were assessed and compared to find the best model for diabetes screening in subjects with FPG <7.0 mmol/L. The optimal critical line was determined by maximizing the sum of sensitivity and specificity. Among the enrolled subjects, 730 of them had FPG <7.0 mmol/L, and only 41.7% new diabetes cases were identified using the 1999 World Health Organization FPG criterion (FPG >=7.0 mmol/L). The area under ROC curves generated by the model on FPG-sAGEP was the largest compared with that on FPG HbA1c, sAGEP, HbA1c or FPG in subjects with FPG <7.0 mmol/L. By maximizing the sum of sensitivity and specificity, the optimal critical line was determined as 0.69*FPG + 0.14*sAGEP = 7.03, giving a critical sensitivity of 91.2% in detecting 2h-PG >=11.1 mmol/L, which was significantly higher than that of FPG-HbA1c or HbA1c. The model on FPG-sAGEP improves the efficacy of using FPG alone in detecting diabetes among high-risk Chinese subjects with FPG <7.0 mmol/L, and is worth being promoted for future diabetes screening. PMID- 26368831 TI - What is the status of novel anti-CD20 antibodies for chronic lymphocytic leukemia and are they set to leave rituximab in the shadows? AB - Chronic lymphocytic leukemia/small lymphocytic lymphoma is the most prevalent form of adult leukemia in western countries. Chemotherapy has been the mainstay of treatment for the last several decades. The introduction of biological, targeted agents (e.g., monoclonal antibodies) has dramatically improved treatment options. The addition of rituximab to fludarabine and cyclophosphamide has improved patient outcomes, as compared to fludarabine and cyclophosphamide. Nevertheless, chronic lymphocytic leukemia remains incurable, leaving considerable room for improvement. One approach would be to enhance the activity of the CD20 antibody. The next-generation monoclonal antibody ofatumumab has not demonstrated superiority over rituximab, whereas obinutuzumab-chlorambucil is superior to rituximab-chlorambucil. Recent efforts to combine anti-CD20 antibodies with new targeted therapies offer the potential to move toward alternative non-chemotherapy-based treatment approaches. PMID- 26368832 TI - Highly Stereoselective Synthesis of Terminal Chloro-Substituted Propargylamines and Further Functionalization. AB - The highly stereoselective addition of lithiated chloroacetylene, derived in situ from cis-1,2-dichloroethene and methyl lithium, to Ellman chiral N-tert butanesulfinyl imines is reported. The reaction proceeds in high yield (up to 98%) and with excellent diastereoselectivity (up to >20:1) for a variety of aryl, heteroaromatic, alkyl, and alpha,beta-unsaturated imine substrates. Transformations of the terminal chloro-substituted propargylamine products are described in which lithium-halogen exchange yields nucleophilic acetylides that can be quenched to yield terminal alkynes or intercepted by carbon electrophiles. PMID- 26368833 TI - Effects of Vestibular Rehabilitation on Balance Control in Older People with Chronic Dizziness: A Randomized Clinical Trial. AB - OBJECTIVE: The aim of this study was to compare the effects of vestibular rehabilitation protocols on balance control in elderly with dizziness. DESIGN: This is a randomized clinical trial with 3-mo follow-up period. The sample was composed of 82 older individuals with chronic dizziness from vestibular disorders. The control group was treated according to the Conventional Cawthorne & Cooksey protocol (n = 40), and the experimental group was submitted to a Multimodal Cawthorne & Cooksey protocol (n = 42). Measures included Dynamic Gait Index, fall history, hand grip strength, Time Up-and-Go Test, sit-to-stand test, multidirectional reach, and static balance tests. RESULTS: With the exception of history of falls, Forward Functional Reach, Unipedal Right and Left Leg Eyes Closed, and Sensorial Romberg Eyes Open, all outcomes improved after treatments. Such results persisted at follow-up period, with the exception of the Tandem Eyes Open and the Timed Up-and-Go manual. The between-group differences for Sensorial Romberg Eyes Closed (4.27 secs) and Unipedal Left Leg Eyes Open (4.08 secs) were significant after treatment, favoring the Multimodal protocol. CONCLUSIONS: Both protocols resulted in improvement on elderly's balance control, which was maintained during a short-term period. The multimodal protocol presented better performance on specific static balance tests. PMID- 26368834 TI - Effects of Induced Volitional Fatigue on Sprint and Jump Performance in Paralympic Athletes with Cerebral Palsy. AB - OBJECTIVE: This study investigated performance, neuromuscular characteristics, and fatigue in Paralympic athletes with cerebral palsy (CP) during a maximal explosive performance trial, compared with well-trained, sprint-specific able bodied athletes. DESIGN: Six Paralympic athletes with hemiplegic CP and 12 able bodied athletes performed one 40-m sprint test (in seconds) and Vertical Jump Tests off both legs (in centimeters), the affected leg individually (in centimeters), and the nonaffected leg individually (in centimeters) before and after an adapted Multistage Shuttle Run Test to exhaustion. Electromyography of five bilateral muscles was measured for mean amplitude (percentage maximum activation). RESULTS: The 40-m sprint test, Vertical Jump Test off both legs, and Vertical Jump Test off the affected leg were significantly compromised in the CP group, whereas the Vertical Jump Test off the nonaffected leg was similar between groups (P < 0.05). Both groups fatigued similarly in performance and electromyography. Affected side electromyography was higher than nonaffected electromyography in the Vertical Jump Test off both legs and Vertical Jump Test off the affected leg in both groups. CONCLUSIONS: The similarity in fatigue between CP and able-bodied groups confirms that Paralympic athletes with CP may have overcome deficits associated with CP documented in sedentary children. The identified asymmetry may assist with a deeper understanding of performance deficits in CP, as it is indicated that activity generated by both legs is performed toward the capacity of the affected leg. PMID- 26368835 TI - Double Disassociation of Anosognosia for Alexia and Simultanagnosia but Quantitative Awareness of Optic Ataxia. AB - A 66-yr-old man with a history of atrial fibrillation and a pacemaker developed sudden onset confusion, disorientation, and visual disturbance without motor weakness. Clinically, significant deficits were found in reading (alexia) and simultaneous multiobject perception (simultanagnosia), both of which the patient denied limitation in, and in vision-right hemianopsia-which he readily acknowledged. Visual acuity in the left visual field was normal. The patient also demonstrated a symptom of optic ataxia-a lack of coordination between visual inputs and hand movements-a deficit he also acknowledged. Work-up with computed topography revealed a left posterior cerebral artery infarct affecting the occipital lobe and extending to involve the parietal lobe and the splenium of the corpus callosum. The authors describe and discuss this fascinating case-the first case to their knowledge of a double disassociation of anosognosia for alexia and simultanagnosia but full, indeed quantitative, awareness of hemianopsia and optic ataxia. This case may be informative on the mechanism of anosognosia in general and supports intentional feed-forward and exemplar reafference models. With regard to the rehabilitation process, appreciation that a patient has anosognosia for various deficits is crucial in recovery and health maintenance. PMID- 26368836 TI - Symptom-Based Treatment of Neuropathic Pain in Spinal Cord-Injured Patients: A Randomized Crossover Clinical Trial. AB - OBJECTIVE: The objective of this study was to identify the differences in medication effect according to pain characteristics in spinal cord-injured patients. METHODS: This study is a prospective, randomized, crossover study. Fifty-five patients and 66 locations of neuropathic pain were included. Pain was classified into four spontaneous characteristics and three evoked pain characteristics. Oxcarbazepine (Na channel blocker) and pregabalin (calcium channel alpha2-delta ligand medication) were tried. Patients were divided into two groups: evoked pain present and evoked pain absent. Overall average visual analog scale was obtained. RESULTS: Oxcarbazepine was significantly more effective for patients without evoked pain than in those with it for electrical, burning, and pricking pain. The effect of pregabalin was not different regarding the presence or absence of evoked pain for all pain categories, except burning pain. In patients with evoked pain, pregabalin was shown to be significantly more effective for electrical pain, allodynia, and heat hyperalgesia than oxcarbazepine. In the evoked pain absent group, oxcarbazepine showed greater improvement than pregabalin but was not significant. CONCLUSIONS: In summary, the phenotype of neuropathic pain was associated with the efficacy of different pharmacologic treatments. Symptom-based treatment, therefore, can lead to more efficient analgesia. PMID- 26368837 TI - Contribution of Axial Motor Impairment to Physical Inactivity in Parkinson Disease. AB - OBJECTIVE: The objective of this study was to investigate the relationships between motor symptoms of Parkinson disease (PD) and activity limitations in persons with PD. DESIGN/METHODS: This is a cross-sectional study of persons with mild to moderate PD (N = 90). Associations among axial motor features, limb motor signs, the Physical Activity Scale for the Elderly, the ability to perform Activities of Daily Living (ADLs), and level of ADL dependency were studied. A composite score of axial motor features included the following Unified Parkinson Disease Rating Scale items: speech, rigidity of the neck, arising from chair, posture, gait, and postural stability. A composite score of limb motor signs included the following Unified Parkinson Disease Rating Scale items: tremor at rest of all extremities, action tremor, rigidity of all extremities, finger taps, hand movement, rapid alternating hand movements, and foot tapping. RESULTS: Axial motor features of PD were significantly correlated with physical inactivity (P < 0.001), decreased ADL (P < 0.001), and increase in ADL dependency (P < 0.001). Limb motor signs significantly correlated with decreased ADL (P < 0.001) and level of ADL dependency (P = 0.035) but did not correlate with physical inactivity. After controlling for age, sex, disease duration, and comorbidity, axial motor features contributed significantly to physical inactivity, decreased ADL, and increase in ADL dependency, whereas the limb motor signs did not. CONCLUSIONS: Axial motor impairment contributed to physical inactivity and decreased ability to perform ADLs in persons with PD. PMID- 26368838 TI - No Pain, No Pigment. PMID- 26368830 TI - Improved imputation of low-frequency and rare variants using the UK10K haplotype reference panel. AB - Imputing genotypes from reference panels created by whole-genome sequencing (WGS) provides a cost-effective strategy for augmenting the single-nucleotide polymorphism (SNP) content of genome-wide arrays. The UK10K Cohorts project has generated a data set of 3,781 whole genomes sequenced at low depth (average 7x), aiming to exhaustively characterize genetic variation down to 0.1% minor allele frequency in the British population. Here we demonstrate the value of this resource for improving imputation accuracy at rare and low-frequency variants in both a UK and an Italian population. We show that large increases in imputation accuracy can be achieved by re-phasing WGS reference panels after initial genotype calling. We also present a method for combining WGS panels to improve variant coverage and downstream imputation accuracy, which we illustrate by integrating 7,562 WGS haplotypes from the UK10K project with 2,184 haplotypes from the 1000 Genomes Project. Finally, we introduce a novel approximation that maintains speed without sacrificing imputation accuracy for rare variants. PMID- 26368839 TI - How Does Confinement Change Ligand-Receptor Binding Equilibrium? Protein Binding in Nanopores and Nanochannels. AB - We present systematic studies for the binding of small model proteins to ligands attached to the inner walls of long nanochannels and short nanopores by polymeric tethers. Binding of proteins to specific ligands inside nanometric channels and pores leads to changes in their ionic conductance, which have been exploited in sensors that quantify the concentration of the proteins in solution. The theoretical predictions presented in this work are aimed to provide a fundamental understanding of protein binding under geometrically confined environments and to guide the design of this kind of nanochannel-based sensors. The theory predicts that the fraction of the channel volume filled by bound proteins is a nonmonotonic function of the channel radius, the length of the tethers, the surface density of the ligands and the size of the proteins. Notably, increasing the density of ligands, decreasing the size of the channel or increasing the size of the protein may lead to a decrease of the fraction of the channel volume filled by bound proteins. These results are explained from the incomplete binding of proteins to the ligands due to repulsive protein-protein and protein-ligand steric interactions. Our work suggests strategies to optimize the change in conductance due to protein binding, for example: (i) proteins much smaller than the radius of the channel may effectively block the channel if tethers of appropriate length are used, and (ii) a large decrease in conductance upon protein binding can be achieved if the channel and the protein are oppositely charged. PMID- 26368840 TI - Longitudinally Extensive Nitrous Oxide Myelopathy With Novel Radiographic Features. PMID- 26368841 TI - Vehicular Emission Ratios of VOCs in a Megacity Impacted by Extensive Ethanol Use: Results of Ambient Measurements in Sao Paulo, Brazil. AB - The Sao Paulo Metropolitan Area (SPMA) is a megacity with 20 million people and over 8 million vehicles. Over the past decade a large increase in biofuel usage, more notably ethanol by light-duty vehicles, has made Brazil, and in particular Sao Paulo, a unique case worldwide. This study presents the first assessment of emission ratios of a selected group of volatile organic compounds (VOCs) relative to carbon monoxide (CO) under ambient conditions. The VOCs studied here include aromatics such as benzene (1.03 pptv/ppbv CO), toluene (3.10 pptv/ppbv CO) and Oxygenated VOCs such as methanol (5.39 pptv/ppbv CO), acetaldehyde (3.93 pptv/ppbv CO), acetone (3.59 pptv/ppbv CO), methyl ethyl ketone (1.42 pptv/ppbv CO), and others. Despite the specificity of the fuel composition, emission ratios were in surprisingly close agreement with other megacities in Europe or in North America. Such results include species whose emission factors have been previously reported to decline (e.g., benzene) or increase (e.g., acetaldehyde) with ethanol usage. Furthermore, diurnal profiles and temperature analysis aid separating the primary anthropogenic, secondary or biogenic components of the species studied here. This study shows that a significant fraction of ethanol in gasoline blends does not result in a well-defined trend in VOC emission profile and certainly motivates further studies. PMID- 26368842 TI - HLA-G 14-bp Ins/Ins Genotype in Patients Harbouring Helicobacter pylori Infection: A Potential Risk Factor? AB - H. pylori is a potent pathogen due to its capacity to successfully evade host defence mechanisms. Despite inducing immune responses in infected individuals, sometimes these responses fail to clear the infection and the bacterium establishes a persistent infection leading to chronic inflammation. In this context, we hypothesized that human leucocyte antigen G (HLA-G), a non-classical major histocompatibility complex molecule that has the ability to regulate immune responses both in physiological and in pathological conditions, may play an important role in promoting tolerance and helping H. pylori to subvert host defence and consequently establish a chronic infection. Therefore, we evaluated the expression of HLA-G 14-bp Ins/Del polymorphism in patients harbouring H. pylori infection, as well as their relationship with histological and demographic variables, to gain a better understanding of the actual role of HLA-G and its genetic polymorphisms in bacterial infection. Sixty-eight patients with clinical symptoms suggestive of H. pylori infection were enrolled to assess HLA-G 14-bp Ins/Del polymorphism allele and genotype frequencies. After adjustment for covariates (age and gender), the odds of having the genotype Ins/Ins, compared to Del/Del, were 3.77 times greater among HP+ cases than among controls. These findings suggest that the 14-bp Ins/Ins genotype, already associated with inflammatory and autoimmune diseases as well as some viral and parasitic infections, could confer a greater risk of developing H. pylori infection. PMID- 26368843 TI - Environmental enrichment induces early heroin abstinence in an animal conflict model. AB - RATIONALE AND OBJECTIVES: Heroin addiction is a significant health and societal problem for which there is no highly effective long-term behavioral or pharmacological treatment. Therefore, strategies that support heroin abstinence should be a primary focus of heroin treatment research. To this end, the current study used an animal conflict model that captures the aversive consequences of drug seeking (as are typical in humans, e.g., incarceration and job loss) to induce abstinence. Using this abstinence model, we examined the capacity of environmental enrichment (EE) to facilitate abstinence in heroin seeking rats. METHODS: The procedure consisted of two phases: drug self-administration (phase 1) and electric barrier application (phase 2) that resulted in abstinence. For phase 1, male rats were trained to self-administer intravenous heroin under a fixed-ratio schedule of reinforcement. After self-administration was acquired, animals were housed either in EE or standard cages (non-EE control). During abstinence in phase 2, the electric barrier was introduced in the operant conditioning chambers by electrifying the floor area near the levers. RESULTS: We found that EE rats achieved abstinence (zero active lever presses for 3 consecutive sessions) in significantly fewer sessions than NEE rats. Further, EE rats abstained at significantly lower electric currents than NEE rats. CONCLUSIONS: EE facilitated abstinence in the conflict model. The current use of the abstinence-conflict model to investigate EE as a behavioral strategy to facilitate abstinence will help in the development of effective treatments for human addicts by bringing together the positive consequences of abstinent behavior in an enriched environment with the aversive consequences of drug seeking. PMID- 26368844 TI - GABA(A) receptors in the central amygdala are involved in memory retention deficits induced by cannabinoids in rats. AB - The central nucleus of the amygdala (CeA) as the main output of amygdala plays an important role in memory processes. In this study we first evaluated the effects of intra-CeA administrations of different doses of a cannabinoid CB1 agonist, WIN55, 212-2, GABA(A) receptor agonist and antagonist, muscimol and bicuculline, alone on memory retention using passive avoidance learning (PAL) test in rats. Then we examined the effects of GABA(A) receptor agents on the responses induced by intra-CeA microinjection of different doses of WIN55, 212-2. We found that administration of WIN55, 212-2 (0.05, 0.1, 0.2 and 0.4MUg/rat) immediately after training impaired memory retrieval in a dose-dependent fashion. Although pre-test intra-CeA administration of muscimol (125, 250 and 500ng/rat) alone had no effect on the step-through latency, its co-administration (125ng/rat) with different doses of WIN55, 212-2 potentiated the amnesic effects of any doses of WIN55, 212 2. The results also showed that pre-test intra-CeA administration of bicuculline (200, 400 and 800ng/rat) alone had no significant effect, but at dose of 200ng/rat disrupted post-training WIN55, 212-2-induced amnesia in the retention test. Furthermore, the additional effect of muscimol (125ng/rat) on memory impairment induced by WIN55, 212-2 (0.1MUg/rat) was prevented by intra-CeA co injection of bicuculline (200ng/rat). We indicated that stimulating or blocking GAGA(A) receptors in the CeA by muscimol and bicuculline interfere with WIN55, 212-2-induced deficits in memory retention in a PAL task and therefore suggests an interaction between cannabinergic and GABAergic systems of the CeA in memory process. PMID- 26368845 TI - deltaV1-1 Reduces Pulmonary Ischemia Reperfusion-Induced Lung Injury by Inhibiting Necrosis and Mitochondrial Localization of PKCdelta and p53. AB - Ischemia-reperfusion (IR)-induced lung injury is one of the major contributing factors of morbidity and mortality after lung transplantation. To determine the IR-induced molecular changes in lung epithelial cells, we developed a cell culture model that simulates lung preservation and transplantation. Six hours of cold ischemic time (CIT) and reperfusion elicited production of multiple inflammatory cytokines and chemokines and increased expression of endoplasmic reticulum (ER) proteins. Prolonged hypothermic condition (18 h CIT) reduced ER stress protein levels, and induced apoptosis and necrosis (via mechanisms related to mitochondrial permeability transition pore opening). Protein kinase C (PKCdelta) was activated during CIT, and its downregulation via small interference (si) (in siRNA) RNA reduced IR-induced cytokine production and apoptotic cell death. deltaV1-1, a PKCdelta peptide inhibitor, reduced translocation of PKCdelta and p53 to the mitochondria after 18 h CIT, rescued ER stress protein expression, and converted the major mode of cell death from necrosis to apoptosis. Administration of deltaV1-1 effectively reduced lung transplantation and IR-induced pulmonary injury in rats. Therefore, inhibition of PKCdelta by deltaV1-1 could be an effective strategy to ameliorate IR-induced lung injury by inhibiting the signaling pathways leading to necrosis. PMID- 26368846 TI - Development of the brain's structural network efficiency in early adolescence: A longitudinal DTI twin study. AB - The brain is a network and our intelligence depends in part on the efficiency of this network. The network of adolescents differs from that of adults suggesting developmental changes. However, whether the network changes over time at the individual level and, if so, how this relates to intelligence, is unresolved in adolescence. In addition, the influence of genetic factors in the developing network is not known. Therefore, in a longitudinal study of 162 healthy adolescent twins and their siblings (mean age at baseline 9.9 [range 9.0-15.0] years), we mapped local and global structural network efficiency of cerebral fiber pathways (weighted with mean FA and streamline count) and assessed intelligence over a three-year interval. We find that the efficiency of the brain's structural network is highly heritable (locally up to 74%). FA-based local and global efficiency increases during early adolescence. Streamline count based local efficiency both increases and decreases, and global efficiency reorganizes to a net decrease. Local FA-based efficiency was correlated to IQ. Moreover, increases in FA-based network efficiency (global and local) and decreases in streamline count based local efficiency are related to increases in intellectual functioning. Individual changes in intelligence and local FA-based efficiency appear to go hand in hand in frontal and temporal areas. More widespread local decreases in streamline count based efficiency (frontal cingulate and occipital) are correlated with increases in intelligence. We conclude that the teenage brain is a network in progress in which individual differences in maturation relate to level of intellectual functioning. PMID- 26368847 TI - Principles of dielectric blood coagulometry as a comprehensive coagulation test. AB - Dielectric blood coagulometry (DBCM) is intended to support hemostasis management by providing comprehensive information on blood coagulation from automated, time dependent measurements of whole blood dielectric spectra. We discuss the relationship between the series of blood coagulation reactions, especially the aggregation and deformation of erythrocytes, and the dielectric response with the help of clot structure electron microscope observations. Dielectric response to the spontaneous coagulation after recalcification presented three distinct phases that correspond to (P1) rouleau formation before the onset of clotting, (P2) erythrocyte aggregation and reconstitution of aggregates accompanying early fibrin formation, and (P3) erythrocyte shape transformation and/or structure changes within aggregates after the stable fibrin network is formed and platelet contraction occurs. Disappearance of the second phase was observed upon addition of tissue factor and ellagic acid for activation of extrinsic and intrinsic pathways, respectively, which is attributable to accelerated thrombin generation. A series of control experiments revealed that the amplitude and/or quickness of dielectric response reflect platelet function, fibrin polymerization, fibrinolysis activity, and heparin activity. Therefore, DBCM sensitively measures blood coagulation via erythrocytes aggregation and shape changes and their impact on the dielectric permittivity, making possible the development of the battery of assays needed for comprehensive coagulation testing. PMID- 26368848 TI - Impact of bodyweight/body mass index on the effectiveness of emergency contraception with levonorgestrel: a pooled-analysis of three randomized controlled trials. AB - OBJECTIVE: A pooled analysis of two randomized controlled trials (RCTs) suggested that increased bodyweight and body mass index (BMI) may be associated with a greater probability of pregnancy. To address this issue we investigated whether higher bodyweight and/or BMI negatively impacted the risk of pregnancy in women receiving LNG-EC (levonorgestrel - emergency contraception) after unprotected sexual intercourse in a pooled analysis of three large multinational RCTs conducted by the World Health Organization (WHO). METHODS: A pooled analysis of three double-blind, multinational RCTs conducted by the WHO to investigate the efficacy of LNG-EC in the general population. All analyses were done on the per protocol set (PPS) which included 5812 women who received LNG-EC within 72 hours following unprotected sexual intercourse. The analysis was based on logistic regression, with pregnancy as the outcome. BMI and weight were represented in the same model. RESULTS: A total of 56 pregnancies were available for analysis in the PPS. Increasing bodyweight and BMI were not correlated with an increased risk of pregnancy in the studied population. A limitation of this study is that despite the large study population in the pooled analysis there were relatively small numbers of women in the high-BMI and high-bodyweight subgroups. CONCLUSION: LNG EC is effective for preventing pregnancy after unprotected intercourse or contraceptive failure and no evidence was found to support the hypothesis of a loss of EC efficacy in subjects with high BMI or bodyweight. Therefore, access to LNG-EC should not be limited only to women of lower bodyweight or BMI. PMID- 26368849 TI - Selective accumulation of the complement membrane attack complex in aging choriocapillaris. AB - The complement membrane attack complex (MAC) shows increased abundance in the choriocapillaris during normal aging and is especially prevalent in age-related macular degeneration (AMD). While perivascular MAC accumulation occurs in the choroid, it is not well understood whether similar deposition occurs in other aging tissues. In this study we examined the abundance of MAC across multiple human tissues. For studies on fixed tissues, paraffin sections were obtained from six human donor eyes and a commercially available tissue array containing 19 different tissues. Immunohistochemical labeling was performed using antibodies directed against the MAC and intercellular adhesion molecule-1 (ICAM-1), as well as the lectin Ulex europaeus agglutinin-I (UEA-I). The choriocapillaris was the only tissue with high levels of the MAC, which was not detected in any of the 38 additional samples from 19 tissues. ICAM-1 was abundantly expressed in the majority of tissues evaluated, and UEA-I labeled the vasculature in all tissues. A second experiment was performed using unfixed frozen sections of RPE-choroid and 7 extraocular tissues, which confirmed the relatively limited localization of the MAC to the choriocapillaris. In comparison to other tissues assessed, the restricted accumulation of MAC in the choriocapillaris may, in part, explain the specificity of AMD to the neural retina, RPE and choroid, and the relative absence of systemic pathology in this disease. PMID- 26368850 TI - Topical application of a G-Quartet aptamer targeting nucleolin attenuates choroidal neovascularization in a model of age-related macular degeneration. AB - Choroidal neovascularization (CNV) associated with the 'wet' form of age related macular degeneration (AMD) is one of the most common causes of central vision loss among the elderly. The 'wet' form of AMD is currently treated by intravitreal delivery of anti-VEGF agents. However, intravitreal injections are associated with complications and long-term inhibition of VEGF leads to macular atrophy. Thus, there is currently an unmet need for the development of therapies for CNV that target molecules other than VEGF. Here, we describe nucleolin as a novel target for the 'wet' form of AMD. Nucleolin was found on the surface of endothelial cells that migrate from the choroid into the subretinal space in the laser-induced model of 'wet' AMD. AS1411 is a previously described G-quartet oligonucleotide that has been shown to bind nucleolin. We found that AS1411 inhibited the formation of tubes by human umbilical vein endothelial cells (HUVECs) by approximately 27.4% in vitro. AS1411 co-localized with the site of laser induced CNV in vivo. Intravitreally injected AS1411 inhibited laser-induced CNV by 37.6% and attenuated infiltration of macrophages by 40.3%. Finally, topical application of AS1411 led to a 43.4% reduction in CNV. Our observations have potential implications for the development of therapies for CNV and specifically for the 'wet' form of AMD. PMID- 26368851 TI - Neonatal aphakia is associated with altered levels of dopamine metabolites in the non-human primate retina. AB - Neonatal aphakia is associated with retardation of the axial elongation of the neonatal eye. In contrast, form deprivation increases axial elongation, an effect that has been associated with decreased retinal dopamine metabolism. The present investigation was conducted to test the hypothesis that neonatal aphakia induces an effect on the levels of retinal dopamine opposite to form deprivation. Lensectomy and vitrectomy were performed on the right eyes of rhesus monkeys at approximately 1 week of age; their left eyes were unmanipulated. Axial length was measured by A-scan ultrasonography. Prior to surgery, mean axial length of the right and left eyes was identical. Following lens removal, both eyes continued to elongate, however the aphakic eyes elongated at a slower rate resulting in a significant shorter axial length compared to that of the unmanipulated eye. Removal of the crystalline lens had no effect on steady-state dopamine levels in either central or peripheral retina. However, levels of the dopamine metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid were significantly elevated in central retina, but not in the peripheral retina of aphakic eyes. Our results support the hypothesis that dopamine is a component of the retinal signaling pathways that are involved in the regulation of eye growth and emmetropization. PMID- 26368852 TI - Controlled Transcription of Exogenous mRNA in Platelets Using Protocells. AB - Transcribing exogenous RNA in eukaryotic cells requires delivering DNA to their nuclei and changing their genome. Nuclear delivery is often inefficient, limiting the potential scope of gene therapy and synthetic biology. These challenges may be overcome by techniques that allow for extranucleate transcription within eukaryotic cells. Protocells have been developed that enable transcription inside of liposomes; however, it has not yet been demonstrated whether this technology can be extended for use within eukaryotic cells. Here we show RNA-synthesizing nanoliposomes allow transcription of exogenous RNA inside anucleate cells. To accomplish this, components of transcription were encapsulated into liposomes and delivered to platelets. These liposomes were capable of light-induced transcription in platelets, providing proof-of-concept that protocell technology can be adapted for use within mammalian cells. PMID- 26368853 TI - Antimicrobial Peptide Lactoferricin B-Induced Rapid Leakage of Internal Contents from Single Giant Unilamellar Vesicles. AB - Enzymatic digestion of bovine lactoferrin generates lactoferricin B (Lfcin B), a 25-mer peptide with strong antimicrobial activity of unknown mechanism. To elucidate the mechanistic basis of Lfcin B bactericidal activity, we investigated the interaction of Lfcin B with Escherichia coli and liposomes of lipid membranes. Lfcin B induced the influx of a membrane-impermeant fluorescent probe, SYTOX green, from the outside of E. coli into its cytoplasm. Lfcin B induced gradual leakage of calcein from large unilamellar vesicles (LUVs) of dioleoylphosphatidylglycerol (DOPG)/dioleoylphosphatidylcholine (DOPC) membranes. To clarify the cause of Lfcin B-induced leakage of calcein from the LUVs, we used the single giant unilamellar vesicle (GUV) method to investigate the interaction of Lfcin B with calcein-containing DOPG/DOPC-GUVs. We observed that a rapid leakage of calcein from a GUV started stochastically; statistical analysis provided a rate constant for Lfcin B-induced pore formation, kp. On the other hand, phase-contrast microscopic images revealed that Lfcin B induced a rapid leakage of sucrose from the single GUVs with concomitant appearance of a spherical GUV of smaller diameter. Because of the very fast leakage, and at the present time resolution of the experiments (33 ms), we could not follow the evolution of pore nor the process of the structural changes of the GUV. Here we used the term "local rupture" to express the rapid leakage of sucrose and determined the rate constant of local rupture, kL. On the basis of the comparison between kp and kL, we concluded that the leakage of calcein from single GUVs occurred as a result of a local rupture in the GUVs and that smaller pores inducing leakage of calcein were not formed before the local rupture. The results of the effect of the surface charge density of lipid membranes and that of salt concentration in buffer on kp clearly show that kp increases with an increase in the extent of electrostatic interactions due to the surface charges. Analysis of Lfcin B-induced shape changes indicated that the binding of Lfcin B increased the area of the outer monolayer of GUVs. These results indicate that Lfcin B-induced damage of the plasma membrane of E. coli with its concomitant rapid leakage of internal contents is a key factor for the bactericidal activity of LfcinB. PMID- 26368854 TI - Low Back Pain in Adolescents: A 1-Year Analysis of Eventual Diagnoses. AB - BACKGROUND: Back pain in adolescents is very common and often seen in the office for evaluation of potential spinal pathology. Pediatric back pain has often thought to be from serious identifiable causes such as spondylolysis, spondylolisthesis, tumor, or infection. A follow-up analysis of adolescents initially presenting with back pain to their eventual subsequent diagnosis within 1 year has not been reported on a large scale with a national sample. METHODS: A national insurance database (PearlDiver Patient Records Database) was queried for ICD-9 codes to identify patients aged 10 to 19 years with back pain from 2007 to 2010. These patients were tracked for imaging obtained, and eventual development of subsequent associated spinal pathology diagnoses using CPT and ICD-9 codes for up to 1 year after initial presentation. RESULTS: A total of 215,592 adolescents were identified presenting with low back pain (LBP) from 2007 to 2010. Over 80% of adolescents with LBP had no identifiable diagnosis within 1 year. The most common associated subsequent diagnoses were lumbar strain/spasm (8.9%), followed by scoliosis (4.7%), lumbar degenerative disk disease (1.7%), and lumbar disk herniation (1.3%). The rates of all other diagnoses including spondylolysis, spondylolisthesis, infection, tumor, and fracture had <1% association with LBP. CONCLUSIONS: In conclusion, adolescent LBP is a common diagnosis for which underlying serious pathology is rare. The most common diagnosis aside from strain or muscle spasm associated with LBP are scoliosis and degenerative disk disease. Pediatric orthopaedists often are consulted on patients with LBP and should always have high suspicion for potential serious spinal pathology, but should recognize the most common etiologies of back pain in adolescence. LEVEL OF EVIDENCE: Level IV-case series. PMID- 26368855 TI - A Modification to the McHale Procedure Reduces Operative Time and Blood Loss. AB - BACKGROUND: Treatment of symptomatic spastic hip dislocations in adolescent patients with cerebral palsy includes a variety of described salvage type procedures. In 1990, McHale and colleagues described a technique involving a femoral head resection, valgus-producing proximal femoral osteotomy, and advancement of the lesser trochanter into the acetabulum. We have modified this technique in 3 ways by: performing it in the lateral position with a more posterior approach, not advancing the lesser trochanter into the acetabulum, and closing the capsule over the acetabulum. The purpose of this paper is to describe our technique and to compare the results to Castle type procedures and McHale procedures performed as originally described. METHODS: We retrospectively reviewed all salvage type procedures performed at our institution for spastic hip dislocations in children with cerebral palsy from 2003 to 2013. Preoperative and postoperative pain, estimated blood loss, operative time, length of stay in the hospital, and postoperative pelvis radiographs were reviewed for heterotopic ossification formation and proximal femoral migration. RESULTS: Twenty-six patients with 30 hip procedures were reviewed. The modified McHale technique had shorter operative times when compared with the supine McHale technique and the Castle procedure (134, 171, and 139 min, respectively). There was a trend toward less blood loss in the modified McHale technique, but this was not significant. There was no difference in length of stay in the hospital. The majority of McHale patients (>63%) had pain relief postoperatively, where half of the Castle patients required a revision surgery for pain (4 of 8). There was less heterotopic ossification seen in the modified McHale technique (6.25%) when compared with supine McHale and Castle techniques (both 50%). However, there was more proximal femoral migration in the modified McHale group. CONCLUSIONS: The modified McHale technique is faster with otherwise equivocal results in the immediate operative periods. There is less heterotopic bone formation but more proximal femoral migration with this new technique. LEVEL OF EVIDENCE: Level IV case series. PMID- 26368856 TI - Transfer of Pectoralis Major to Subscapularis in the Management of Brachial Plexus Birth Palsy Sequels. AB - BACKGROUND: Limitations in abduction and external rotation are the sequel of brachial palsy. The purpose of this study was to evaluate functional outcomes of modified L'Episcopo procedure in children with brachial palsy who do not have gross shoulder joint subluxation. METHODS: From 2002 to 2012, a continuous series of 22 patients with brachial plexus birth palsy underwent a modified L'Episcopo procedure. Through an axillary approach, subscapularis release with latissimus dorsi rerouting and transfer of pectoralis major to subscapularis footprint was performed. RESULTS: The mean age of patients at surgery was 49 months. The mean follow-up time was 51 months (range, 24 to 90 mo). Preoperatively, the mean active abduction and external rotation were 77.5 and 2.5 degrees, respectively. The mean active abduction and external rotation were 135.6 and 32 degrees, respectively, at the final follow-up (P<0.001). CONCLUSIONS: This modified L'Episcopo technique is an effective and reproducible procedure that improves shoulder function significantly. LEVEL OF EVIDENCE: Level III. PMID- 26368857 TI - Lemierre Disease: A Case With Multilevel Epidural Abscess and Aggressive Neurological Weakness: Case Report and Literature Review. AB - BACKGROUND: Lemierre disease is a rare postanginal sepsis caused by the anaerobe Fusobacterium necrophorum. It is associated with a pharyngitis that progresses quickly to thrombophlebitis of the internal jugular vein and metastatic abscesses to pulmonary, soft tissue, articular, and organ systems. It is rarely associated with spinal epidural abscesses. Because of the increasing antibiotic resistance, its incidence is on the rise. METHODS: A single-patient case report of an adolescent male who initially presented to our institution for bacteremia and febrile episodes. Over a 1-week course, he developed severe back pain and progressive lower extremity weakness. Advanced imaging revealed an epidural abscess spanning T2-L3 level with extension into the psoas and the paraspinal musculature. Acute management consisted of broad-spectrum intravenous (IV) antibiotics and hemilaminectomy decompression from T2 to L3. The patient completed a 6-week course of IV antibiotics and was followed for a 1-year time period with close clinical follow-up. RESULTS: Blood cultures identified the infecting organism as F. necrophorum. The combination of IV antibiotics and acute hemilaminectomy decompression resulted in successful clearance of the infecting organism with normalization of inflammatory markers and cultures. The patient noted immediate and sustained neurological improvement, with return of full motor and sensory function. At the 1-year timepoint, the patient was able to return to sports and no sagittal/coronal imbalance was noted on radiographs. CONCLUSIONS: An aggressive case of Lemierre disease with extensive epidural abscess formation and neurological weakness was successfully managed with the combination of IV antibiotics and extensive hemilaminectomies for decompression. The patient exhibited no long-term sequela as a result of either the epidural abscess or of its treatment. LEVEL OF EVIDENCE: Level V. PMID- 26368858 TI - Plate-assisted Lengthening of the Femur and Tibia in Pediatric Patients. AB - BACKGROUND: Limb lengthening over a percutaneous plate can be used during pediatric distraction osteogenesis to decrease the time of external fixation. METHODS: A retrospective, consecutive 2-surgeon experience of pediatric femoral and tibial lengthenings with a plate-assisted lengthening (PAL) technique was performed. The plate was placed at the time of index corticotomy. The primary outcome measures of external fixation index, consolidation index, and complications were assessed for each lengthening. RESULTS: From 2005 to 2012, 38 lengthenings (23 femur, 15 tibia) in 30 patients were performed by a PAL technique. All patients experienced successful distraction and consolidation. The average achieved lengthening was 3.80+/-0.98 cm (range, 2.2 to 6.4) with an average consolidation index of 27 days/cm and a mean external fixation index of 13.1+/-4.29 days/cm (range, 7.8 to 30). Patients returned to full weight-bearing activity after an average of 98.3+/-28.5 days. There were an average of 1.08+/ 1.05 total complications and 0.39+/-0.75 severe complications per lengthening. Complications were encountered most commonly during femoral lengthening, including procurvatum and varus deformity through the regenerate. These deformities were usually corrected by frame adjustment before removal. CONCLUSIONS: PAL is a safe technique that minimizes time of external fixation, accelerates rehabilitation and weight-bearing, and can be successfully used on the femur or tibia. The most common complications are angular deformities of the regenerate that can be treated with adjustment before or at the time of plate locking. LEVEL OF EVIDENCE: Level IV-retrospective case series. PMID- 26368859 TI - Comparing Percutaneous Physeal Epiphysiodesis and Eight-Plate Epiphysiodesis for the Treatment of Limb Length Discrepancy. AB - BACKGROUND: Either percutaneous or eight-plate epiphysiodesis have been shown to be effective growth modulation techniques for the treatment of limb length discrepancies (LLD). However, few studies compared the outcomes of both techniques with some confounding results. The aim of this study was to evaluate the outcomes of the both techniques in the treatment of the LLD. METHODS: Between 2004 and 2012, medical records of all cases that underwent either eight-plate or percutaneous epiphysiodesis (PE) were reviewed. Age at surgery, sex, diagnosis, surgical site (proximal tibia/distal femur), time of follow-up, complications, and additional procedures were noted. Correction of the LLD was evaluated to calculate the rate of correction and the percentage of improvement from the long leg standing x-rays or scanograms, collected at each visit. RESULTS: There were 24 patients in the eight-plate (10 girls and 14 boys) and 48 patients in the PE group (28 girls and 20 boys). No statistically significant difference was found in the age, sex, preoperative LLD, or follow-up between groups. Both groups reached to an average LLD below 2 cm. The percentage of improvement was significantly higher in the PE group (P=0.031). The rate of individual femoral and tibial correction did not differ between the groups. CONCLUSIONS: Both methods are shown to be effective for LLD correction. However, PE led to greater improvement during the same follow-up time with fewer complications and less need for additional surgical procedures. PMID- 26368862 TI - Metabolomics in the Clinical Diagnosis of Inflammatory Bowel Disease. AB - BACKGROUND: Crohn's disease and ulcerative colitis represent the 2 major phenotypes of inflammatory bowel disease (IBD) that are characterized by chronic inflammation of all or parts of the gastrointestinal tract. The pathogenesis of both diseases is influenced by genetic predispositions as well as microbial and environmental factors. Currently, there is an emerging consensus hypothesis that a microbial dysbiosis is involved in initiating the disease or in maintaining it. These compositional alterations may be reflected in altered metabolic activities of the gut microbiota and has led to the use of 'omic' profiling to improve the understanding of the pathophysiology of IBD. Key Messages: In the past few years, a metabolic approach has increasingly been applied in a number of studies of experimental and human IBD which were mostly focused on exploring disease-related metabolites to gain more insight into metabolic pathways. Metabolomics involves the high throughput identification, characterization and quantification of small molecule metabolites by different analytical techniques and has been performed in different biofluids such as serum/plasma, urine or fecal samples. The application of such a metabolite profiling technique has revealed different metabolites that allow the discrimination of IBD patients from healthy controls. In addition, separate IBD subtypes could be differentiated. Some of these metabolic changes were directly associated to alterations of specific gut microbial populations, implying a perturbation in the gut microbiome in the development of IBD. CONCLUSIONS: This review covers the emerging contribution of metabolomics for the discovery of an IBD signature and to identify biomarkers linked with a metabolic imbalance. For the implementation of metabolomics as a diagnostic tool in IBD, large prospective cohort studies are necessary. PMID- 26368861 TI - A man of vision who blazed the trail for children's rights and died a hero's death. PMID- 26368863 TI - Can sequential parallel comparison design and two-way enriched design be useful in medical device clinical trials? AB - Sequential parallel comparison design (SPCD) was proposed for trials with high placebo response. In the first stage of SPCD subjects are randomized between placebo and active treatment. In the second stage placebo nonresponders are re randomized between placebo and active treatment. Data from the population of "all comers" and the subpopulations of placebo nonresponders then combined to yield a single p-value for treatment comparison. Two-way enriched design (TED) is an extension of SPCD where active treatment responders are also re-randomized between placebo and active treatment in Stage 2. This article investigates the potential uses of SPCD and TED in medical device trials. PMID- 26368860 TI - The effect of 5-fluorouracil/leucovorin chemotherapy on CpG methylation, or the confounding role of leukocyte heterogeneity: An illustration. AB - Blood-based epigenome-wide association studies that aim at comparing CpG methylation between colorectal cancer (CRC) patients and controls can lead to the discovery of diagnostic or prognostic biomarkers. Numerous confounders can lead to spurious associations. We aimed to see if 5-fluorouracil (5-FU)/leucovorin chemotherapy administered to cases prior to the collection of their blood has an effect on methylation. 304 patients who received treatment and 273 who did not were profiled on the HumanMethylation450 array. Association tests were adjusted for confounders, including proxies for leukocyte cell counts. There were substantial methylation differences between these two groups that vanished once the leukocyte heterogeneity was accounted for. We observed a significant decrease of T cells in the treatment group (CD4+: p=10(-6); CD8+: p=0.036) and significant increase of NK cells (p=0.05) and monocytes (p=0.0006). 5-FU/leucovorin has no effect on global and local blood-based methylation profiles, other than through differences in the leukocyte compositions that the treatment induced. PMID- 26368864 TI - Effective modulation transfer function measurement method for an off-axis optical system. AB - The most common modulation transfer function (MTF) measurement equipment operates along a coaxial testing light path. It can be used to test several fields along one radial direction and is suitable for an optical system with rotational symmetry. However, off-axis optical systems need multidimensional adjustment and complex mechanical structures to measure the MTF of fields. In this paper, we propose a MTF testing module to address this issue by adding a rotatable mirror to redirect the light. The testing module greatly simplifies MTF measurement of off-axis imaging systems in both the process and mechanism. The figure error of the rotatable mirror is analyzed to ensure testing accuracy. MTF testing of a free-form surface prism using this novel method was successfully implemented and the results are presented. The method can be extended to the measurement of other parameters, such as the effective focal length. PMID- 26368865 TI - Objective shearing digital holography for removing aberration from optical system. AB - We propose a new digital holography based on the lateral shearing interference concept to remove the total aberrations from the reference wave, illumination wave, and the optical elements. It uses three mutually shifted image holograms of the object that are divided from each other to obtain phase differences. The phase aberration can be removed and the original sample phase can be reconstructed by the phase differences. Then, the influence of the stage moving imprecision on the reconstruction quality is analyzed. Optical experiments verified that the proposed method can totally remove the phase aberrations. As a result, the proposed method could be used for ultra-precise optical measurement through eliminating optical phase aberration to increase the measurement accuracy. PMID- 26368866 TI - Application of laser ultrasonic method for on-line monitoring of friction stir spot welding process. AB - Application of a laser ultrasonic method is developed for on-line monitoring of the friction stir spot welding (FSSW) process. Based on the technology of FSSW, laser-generated ultrasonic waves in a good weld and nonweld area are simulated by a finite element method. The reflected and transmitted waves are analyzed to disclose the properties of the welded interface. The noncontact-laser ultrasonic inspection system was established to verify the numerical results. The reflected waves in the good-weld and nonweld area can be distinguished by time-of-flight. The transmitted waves evidently attenuate in the nonweld area in contrast to signal amplitude in the good weld area because of interfacial impedance difference. Laser ultrasonic C-scan images can sufficiently evaluate the intrinsic character of the weld area in comparison with traditional water immersion ultrasonic testing results. The research results confirm that laser ultrasonics would be an effective method to realize the characterization of FSSW defects. PMID- 26368867 TI - Statistical characteristics of aberrations of human eyes after small incision lenticule extraction surgery and analysis of visual performance with individual eye model. AB - Preoperative and postoperative wavefront aberrations of 73 myopic eyes with small incision lenticule extraction surgery are analyzed in this paper. Twenty-eight postoperative individual eye models are constructed to investigate the visual acuity (VA) of human eyes. Results show that in photopic condition, residual defocus, residual astigmatism, and higher-order aberrations are relatively small. 100% of eyes reach a VA of 0.8 or better, and 89.3% of eyes reach a VA of 1.0 or better. In scotopic condition, the residual defocus and the higher-order aberrations are, respectively, 1.9 and 8.5 times the amount of that in photopic condition, and the defocus becomes the main factor attenuating visual performance. PMID- 26368868 TI - Nonlocal imaging of a reflective object using positive and negative correlations. AB - The Hanbury Brown and Twiss (HBT) effect is a classical intensity correlation effect, but it is also widely used in the quantum optics regime, and has led to many important breakthroughs in both basic and applied physics, among which ghost imaging (GI) has aroused particular interest. In this article, the positive and negative intensity correlations in HBT correlation are analyzed, based on which we describe experiments on thermal light nonlocal imaging of a reflective object using the positive and negative correlations of correspondence imaging. An improvement of 16.3% in the signal-to-noise ratio of the reconstructed image has been achieved, indicating that this method may have promising potential in future GI applications where noise is a serious problem and smaller sampling numbers are necessary. PMID- 26368869 TI - Average intensity of M * N Gaussian array beams in oceanic turbulence. AB - Based on the power spectrum of oceanic turbulence proposed by Nikishov, the analytical expressions for average intensity of M*N Gaussian array beams propagating in oceanic turbulence are derived, where the coherent and incoherent combinations are considered. Using the focused beam, the intensity can be received at the same point. The changes of the average intensity versus three oceanic parameters are investigated. PMID- 26368870 TI - Acousto-optical tunable filter for combined wideband, spectral, and optical coherence microscopy. AB - A multimodal technique for inspection of microscopic objects by means of wideband optical microscopy, spectral microscopy, and optical coherence microscopy is described, implemented, and tested. The key feature is the spectral selection of light in the output arm of an interferometer with use of the specialized imaging acousto-optical tunable filter. In this filter, two interfering optical beams are diffracted via the same ultrasound wave without destruction of interference image structure. The basic requirements for the acousto-optical tunable filter are defined, and mathematical formulas for calculation of its parameters are derived. Theoretical estimation of the achievable accuracy of the 3D image reconstruction is presented and experimental proofs are given. It is demonstrated that spectral imaging can also be accompanied by measurement of the quantitative reflectance spectra. Examples of inspection of optically transparent and nontransparent samples demonstrate the applicability of the technique. PMID- 26368871 TI - Optical identification based on time domain optical coherence tomography. AB - We present a novel method for optical identification, i.e., authenticating valuable documents such as a passport, credit cards, and bank notes, using optical coherence tomography (OCT). An OCT system can capture three-dimensional (3D) images and visualize the internal structure of an object. In our work, as an object, we consider a multilayered optical identification tag composed of a limited number of thin layers (10-100 MUm thick). The thickness, width, and location of the layers in the tag encode a unique identification information. Reading of the tag is done using a time domain OCT (TD-OCT) system. Typically, a TD-OCT system requires continuous mechanical scanning in one or more directions to get a 3D volume image of an object. The continuous scanning implies a complicated optical setup, which makes an OCT system fragile and expensive. We propose to avoid the conventional scanning by (1) not requiring 3D imaging, and (2) utilizing the motion of the optical tag itself. The motion is introduced to the tag reader, for example, by a user, which replaces the need for conventional scanning. The absence of a conventional scanning mechanism makes the proposed OCT method very simple and suited for identification purposes; however, it also puts some constraints to the construction of the optical tag, which we discuss in this paper in detail. PMID- 26368872 TI - Broadband and transparent wavelength conversion based on dispersion-flattened double-slot waveguide. AB - The flat and low second-order dispersion of 0~-13 ps2/km in a double slot waveguide is optimized for broadband wavelength conversion. Subsequently, a 3 dB conversion bandwidth of about 1200 nm is presented by four-wave mixing based on the above structure in simulation. Attributed to the small phase mismatch caused by low second- and fourth-order dispersion parameter in a large waveband, the 3 dB conversion bandwidth is almost constant at about 1200 nm with the pump wavelength varying from 2200 to 2800 nm. The results indicate that this dispersion-flattened double-slot waveguide is not only an ideal device for broadband wavelength conversion but also can realize the transparency of pump wavelength, which has potential applications in wavelength conversion. PMID- 26368873 TI - Accurate calculation of diffraction-limited encircled and ensquared energy. AB - Mathematical properties of the encircled and ensquared energy functions for the diffraction-limited point-spread function (PSF) are presented. These include power series and a set of linear differential equations that facilitate the accurate calculation of these functions. Asymptotic expressions are derived that provide very accurate estimates for the relative amount of energy in the diffraction PSF that fall outside a square or rectangular large detector. Tables with accurate values of the encircled and ensquared energy functions are also presented. PMID- 26368874 TI - Strain and mechanical properties of the VCM multilayer sheet and their composites using the digital speckle correlation method. AB - The digital speckle correlation method (DSCM) is introduced to solve the challenging problems in the related geometric measurement. Theoretical calculations of strain are deduced using the DSCM. Corresponding strains along x and y directions are obtained from uniaxial tension experiments and digital speckle measurements, using the VCM nondeep drawing multilayer sheet, the VCM deep-drawing multilayer sheet, clad films, nondeep drawing substrate, and deep drawing substrate sheet as the targeted experimental objects. The results show that the maximum strains along the x direction of the VCM nondeep drawing multilayer sheet, the VCM deep-drawing multilayer sheet, clad film, nondeep drawing substrate, and deep-drawing substrate sheet are 68.473%, 48.632%, 91.632%, 50.784% and 40.068%, respectively, while the maximum strains along the y direction are -2.657%, -15.381%, 2.826%, -9.780% and -7.783%, respectively. The mechanical properties of the VCM multilayer sheet are between those of the substrate and clad film, while mechanical properties of the VCM deep-drawing multilayer sheet are superior to those of the VCM nondeep drawing multi-layer sheet. PMID- 26368875 TI - Robust commercial diffuse reflector for UV-VIS-NIR applications. AB - We report the development and testing of a new commercially available diffuse reflecting material with reflectivities in the visible comparable to industry leading products. This new diffuse reflector consists of solid quartz in which there is a dense distribution of tiny pockets of air. The multiple reflections by the quartz-air interfaces of these air pockets transforms a highly transmissive base material into a highly diffuse reflecting material. PMID- 26368876 TI - Cosine apodization of dual-resonance all-fiber acousto-optic tunable filters. AB - We experimentally demonstrate a novel cosine apodization technique for dual resonance all-fiber acoustic-optic tunable filter. The technique is based on a hybrid control of input acoustic polarization state and circumferential fiber twist. We will show that intrinsic sidelobe spectra occurring between dual filtering bands are successfully suppressed through our approach, which will be also theoretically confirmed via our analytical and numerical studies. The results illustrate that the spectral positions of each resonance are tuned linearly and continuously by the fiber twist, and that overall sidelobe spectra between two resonances are suppressed regardless of fiber twist angle. The proposed scheme is useful to minimize cross talk between adjacent wavelength channels in optical sensor systems. We highlight that our approach is directly applicable to low-noise matched filtering. PMID- 26368877 TI - Shaping diffraction-free Lommel beams with digital binary amplitude masks. AB - Here, we report on experimental observations of various Lommel modes that possess distinct diffraction-free behaviors. The binary amplitude masks are designed to accurately encode the complex field information with the superpixel method. Then, the generation of the desired beams is demonstrated with these binary patterns projected onto the digital micromirrors device (DMD). Remarkably, we find that the field distribution and orbital angular momentum can be continuously engineered by tuning the beam parameters. Furthermore, the shape-invariant feature of such beams is verified by their far-field ring-like structures. Our observations are in good accordance with the theoretical predictions, and our methods may find potential applications in optical guiding and imaging. Moreover, apart from the DMD, the binary amplitude hologram can also be presented with well fabricated elements, and thus, our method will also enable new applications for surface plasmon polaritons as well as electron beams. PMID- 26368878 TI - Attitude-correlated frames approach for a star sensor to improve attitude accuracy under highly dynamic conditions. AB - The attitude accuracy of a star sensor decreases rapidly when star images become motion-blurred under dynamic conditions. Existing techniques concentrate on a single frame of star images to solve this problem and improvements are obtained to a certain extent. An attitude-correlated frames (ACF) approach, which concentrates on the features of the attitude transforms of the adjacent star image frames, is proposed to improve upon the existing techniques. The attitude transforms between different star image frames are measured by the strap-down gyro unit precisely. With the ACF method, a much larger star image frame is obtained through the combination of adjacent frames. As a result, the degradation of attitude accuracy caused by motion-blurring are compensated for. The improvement of the attitude accuracy is approximately proportional to the square root of the number of correlated star image frames. Simulations and experimental results indicate that the ACF approach is effective in removing random noises and improving the attitude determination accuracy of the star sensor under highly dynamic conditions. PMID- 26368879 TI - Measuring the contribution of atmospheric scatter to laser eye dazzle. AB - An experiment has been conducted to determine the contribution of atmospheric scatter to the severity of the dazzle experienced by a human under illumination from a visible laser. A 15 W 532 nm laser was propagated over a 380 m outdoor range in San Antonio, Texas, over nine data collection sessions spanning June and July 2014. A narrow acceptance angle detector was used to measure scattered laser radiation within the laser beam at different angles from its axis. Atmospheric conditions were logged via a local weather station, and air quality data were taken from a nearby continuous air monitoring station. The measured laser irradiance data showed very little variation across the sessions and a single fitting equation was derived for the atmospheric scatter function. With very conservative estimates of the scatter from the human eye, atmospheric scatter was found to contribute no more than 5% to the overall veiling luminance across the scene for a human observer experiencing laser eye dazzle. It was concluded that atmospheric scatter does not make a significant contribution to laser eye dazzle for short-range laser engagements in atmospheres of good to moderate air quality, which account for 99.5% of conditions in San Antonio, Texas. PMID- 26368880 TI - Performance analysis of satellite-to-ground downlink coherent optical communications with spatial diversity over Gamma-Gamma atmospheric turbulence. AB - The performances of satellite-to-ground downlink optical communications over Gamma-Gamma distributed atmospheric turbulence are studied for a coherent detection receiving system with spatial diversity. Maximum ratio combining (MRC) and selection combining (SC) techniques are considered as practical schemes to mitigate the atmospheric turbulence. Bit-error rate (BER) performances for binary phase-shift keying modulated coherent detection and outage probabilities are analyzed and compared for SC diversity using analytical results and for MRC diversity through an approximation method with different numbers of receiving aperture each with the same aperture area. To show the net diversity gain of a multiple aperture receiver system, BER performances and outage probabilities of MRC and SC multiple aperture receiver systems are compared with a single monolithic aperture with the same total aperture area (same total average incident optical power) for satellite-to-ground downlink optical communications. All the numerical results are verified by Monte-Carlo simulations. PMID- 26368881 TI - Ultrathin high-index metasurfaces for shaping focused beams. AB - The volume size of a converging wave, which plays a relevant role in image resolution, is governed by the wavelength of the radiation and the numerical aperture (NA) of the wavefront. We designed an ultrathin (lambda/8 width) curved metasurface that is able to transform a focused field into a high-NA optical architecture, thus boosting the transverse and (mainly) on-axis resolution. The elements of the metasurface are metal-insulator subwavelength gratings exhibiting extreme anisotropy with ultrahigh index of refraction for TM polarization. Our results can be applied to nanolithography and optical microscopy. PMID- 26368882 TI - Practical and highly sensitive elemental analysis for aqueous samples containing metal impurities employing electrodeposition on indium-tin oxide film samples and laser-induced shock wave plasma in low-pressure helium gas. AB - We have conducted an experimental study exploring the possible application of laser-induced breakdown spectroscopy (LIBS) for practical and highly sensitive detection of metal impurities in water. The spectrochemical measurements were carried out by means of a 355 nm Nd-YAG laser within N2 and He gas at atmospheric pressures as high as 2 kPa. The aqueous samples were prepared as thin films deposited on indium-tin oxide (ITO) glass by an electrolysis process. The resulting emission spectra suggest that concentrations at parts per billion levels may be achieved for a variety of metal impurities, and it is hence potentially feasible for rapid inspection of water quality in the semiconductor and pharmaceutical industries, as well as for cooling water inspection for possible leakage of radioactivity in nuclear power plants. In view of its relative simplicity, this LIBS equipment offers a practical and less costly alternative to the standard use of inductively coupled plasma-mass spectrometry (ICP-MS) for water samples, and its further potential for in situ and mobile applications. PMID- 26368883 TI - Mineralogy and astrobiology detection using laser remote sensing instrument. AB - A multispectral instrument based on Raman, laser-induced fluorescence (LIF), laser-induced breakdown spectroscopy (LIBS), and a lidar system provides high fidelity scientific investigations, scientific input, and science operation constraints in the context of planetary field campaigns with the Jupiter Europa Robotic Lander and Mars Sample Return mission opportunities. This instrument conducts scientific investigations analogous to investigations anticipated for missions to Mars and Jupiter's icy moons. This combined multispectral instrument is capable of performing Raman and fluorescence spectroscopy out to a >100 m target distance from the rover system and provides single-wavelength atmospheric profiling over long ranges (>20 km). In this article, we will reveal integrated remote Raman, LIF, and lidar technologies for use in robotic and lander-based planetary remote sensing applications. Discussions are focused on recently developed Raman, LIF, and lidar systems in addition to emphasizing surface water ice, surface and subsurface minerals, organics, biogenic, biomarker identification, atmospheric aerosols and clouds distributions, i.e., near-field atmospheric thin layers detection for next robotic-lander based instruments to measure all the above-mentioned parameters. PMID- 26368885 TI - Active polarimetric imager with near infrared laser illumination for adaptive contrast optimization. AB - We designed and built an active polarimetric imager with laser illumination at 1.5 MUm wavelength for adaptive polarimetric contrast optimization. It can generate and analyze any polarization state on the Poincare sphere in order to best adapt to the polarimetric properties of the scene. Polarimetric contrast optimization is performed by analyzing the scene with an ultrafast active-contour based segmentation algorithm. This device is, to the best of our knowledge, the first fully adaptive imager controlled by image processing algorithms for polarimetric contrast enhancement. Its capabilities are illustrated in some examples of real-world decamouflage applications. PMID- 26368884 TI - Simulation-based evaluation of the resolution and quantitative accuracy of temperature-modulated fluorescence tomography. AB - Conventional fluorescence tomography (FT) can recover the distribution of fluorescent agents within a highly scattering medium. However, poor spatial resolution remains its foremost limitation. Previously, we introduced a new fluorescence imaging technique termed "temperature-modulated fluorescence tomography" (TM-FT), which provides high-resolution images of fluorophore distribution. TM-FT is a multimodality technique that combines fluorescence imaging with focused ultrasound to locate thermo-sensitive fluorescence probes using a priori spatial information to drastically improve the resolution of conventional FT. In this paper, we present an extensive simulation study to evaluate the performance of the TM-FT technique on complex phantoms with multiple fluorescent targets of various sizes located at different depths. In addition, the performance of the TM-FT is tested in the presence of background fluorescence. The results obtained using our new method are systematically compared with those obtained with the conventional FT. Overall, TM-FT provides higher resolution and superior quantitative accuracy, making it an ideal candidate for in vivo preclinical and clinical imaging. For example, a 4 mm diameter inclusion positioned in the middle of a synthetic slab geometry phantom (D:40 mm*W:100 mm) is recovered as an elongated object in the conventional FT (x=4.5 mm; y=10.4 mm), while TM-FT recovers it successfully in both directions (x=3.8 mm; y=4.6 mm). As a result, the quantitative accuracy of the TM-FT is superior because it recovers the concentration of the agent with a 22% error, which is in contrast with the 83% error of the conventional FT. PMID- 26368886 TI - Design of compact LED free-form optical system for aeronautical illumination. AB - A type of runway centerline light is designed for the application of light emitting diode (LED) aeronautical illumination. A total internal reflection collimating lens and an integrated prism are designed, respectively, to meet the intensity distribution of International Convention on Civil Aviation (ICAO) regulations. The principle of geometric optics is adopted to construct the free form surfaces of a collimating lens, which is simple. Different variations are used in the process of free-form surface calculation. An integrated prism with a diffuser is used for uniformly diffusing rays and then decreasing the central maximum intensity to avoid glare. The structure of the optical system is compact. Computer simulation results show that an optical efficiency of 79.2% is achieved for a 1 mm*1 mm LED source. Tolerance analysis is carried out to determine tolerance limits of manufacture and installation errors. To verify the optical performance of the proposed runway centerline light, the practical illumination distribution is measured by using Cree XP-E2 LED, which can comply with ICAO regulations. PMID- 26368887 TI - Performance of an optical encoder based on a nondiffractive beam implemented with a specific photodetection integrated circuit and a diffractive optical element. AB - In this paper, we study the incremental signal produced by an optical encoder based on a nondiffractive beam (NDB). The NDB is generated by means of a diffractive optical element (DOE). The detection system is composed by an application specific integrated circuit (ASIC) sensor. The sensor consists of an array of eight concentric annular photodiodes, each one provided with a programmable gain amplifier. In this way, the system is able to synthesize a nonuniform detectivity. The contrast, amplitude, and harmonic content of the sinusoidal output signal are analyzed. The influence of the cross talk among the annular photodiodes is placed in evidence through the dependence of the signal contrast on the wavelength. PMID- 26368888 TI - Airborne ultraviolet imaging system for oil slick surveillance: oil-seawater contrast, imaging concept, signal-to-noise ratio, optical design, and optomechanical model. AB - The airborne ultraviolet imaging system, which assesses oil slick areas better than visible and infrared optical systems, was designed to monitor and track oil slicks in coastal regions. A model was built to achieve the upwelling radiance distribution of oil-covered sea and clean seawater, based on the radiance transfer software. With this model, the oil-seawater contrast, which affects the detection of oil-covered coastal areas, was obtained. The oil-seawater contrast, fundamental imaging concept, analog calculation of SNR, optical design, and optomechanical configuration of the airborne ultraviolet imaging system are illustrated in this paper. The study of an airborne ultraviolet imaging system with F-number 3.4 and a 40 degrees field of view (FOV) in near ultraviolet channel (0.32-0.38 MUm) was illustrated and better imaging quality was achieved. The ground sample distance (GSD) is from 0.35 to 0.7 m with flight height ranges from 0.5 to 1 km. Comparisons of detailed characteristics of the airborne ultraviolet imaging system with the corresponding characteristics of previous ultraviolet systems were tabulated, and these comparisons showed that this system can achieve a wide FOV and a relative high SNR. A virtual mechanical prototype and tolerances analysis are illustrated in this paper to verify the performance of fabrication and assembly of the ultraviolet system. PMID- 26368889 TI - Active control of residual tool marks for freeform optics functionalization by novel biaxial servo assisted fly cutting. AB - The inherent residual tool marks (RTM) with particular patterns highly affect optical functions of the generated freeform optics in fast tool servo or slow tool servo (FTS/STS) diamond turning. In the present study, a novel biaxial servo assisted fly cutting (BSFC) method is developed for flexible control of the RTM to be a functional micro/nanotexture in freeform optics generation, which is generally hard to achieve in FTS/STS diamond turning. In the BSFC system, biaxial servo motions along the z-axis and side-feeding directions are mainly adopted for primary surface generation and RTM control, respectively. Active control of the RTM from the two aspects, namely, undesired effect elimination or effective functionalization, are experimentally demonstrated by fabricating a typical F theta freeform surface with scattering homogenization and two functional microstructures with imposition of secondary phase gratings integrating both reflective and diffractive functions. PMID- 26368890 TI - Comparison of real-time phase-reconstruction methods in temporal speckle-pattern interferometry. AB - Three real-time methods for object-phase recovery are implemented and compared in temporal speckle-pattern interferometry. Empirical mode and intrinsic time-scale decompositions are used and compared as real-time nonstationary and nonlinear filtering techniques for the extraction of the spatio-temporal evolution of the object phase. The proposed real-time methods avoid the application of the Hilbert transform and improve the accuracy of the measurement by filtering under modulated pixels using Delaunay triangulation. The performance of the proposed methods is evaluated by comparing phase-recovery accuracy and computation time by means of numerical simulations and experimental data obtained from common and simultaneous pi/2 phase-shifting heterodyne interferometry. PMID- 26368892 TI - Phase resonances induced by a subwavelength particle near a surface with two cavities. AB - It is well known that finite groove gratings with subwavelength features exhibit phase resonances, which are associated with a particular distribution of the magnetic field phase within the cavities and are characterized by a significant enhancement of the internal field. For a flat surface with identical grooves under symmetrical conditions of incidence, it was shown that a minimum of three cavities is required to excite a phase resonance. In this paper we show that by approaching a particle to the surface, this requirement is removed and the particle enables the excitation of phase resonances even in a system of two identical cavities under normal incidence. The influence of the position and the radius of the particle in the reflected far field response, as well as in the near and internal field, is analyzed. The possibility of exciting phase resonances in this system opens up new means for the design of sensing devices. PMID- 26368891 TI - Emission analysis of a laser-produced barium plasma plume. AB - In the present work we report the characteristic emission features of a laser produced barium plasma plume. The time-resolved analysis for the different spectral lines of neutral and singly charged ionic barium has been carried out. It has been observed that the temporal evolution of electron temperature and density shows a peculiar behavior which is significantly different from the reported results of laser ablation of materials. The electron density increases with increase in delay time but the temperature does not change to any significant extent. Strong self-reversal in the emission of a resonant singly charged barium ionic line (455.4 nm) with time delay indicates the increase of population of singly charged barium ion with time. The results are explained on the basis of the increased population of barium metastables and subsequent ionization (Penning type). PMID- 26368893 TI - Monostatic all-fiber rangefinder system. AB - A rangefinder based on a fiber-coupled, monostatic system that transmits and receives through the same aperture has been developed. Some of the advantageous characteristics include elimination of the requirement for precision alignment of the receiver detector and smaller size than bistatic systems using separate transmit and receive apertures. Because there is no parallax between transmit and receive beam paths, optimum receiver alignment is maintained for all ranges. The system operates at 50 kpps and uses a 27 mm diameter/40 mm focal length transmit/receive lens. The standard deviation range precision of the system is 7.8 mm at 50 m with 3.3 MUJ pulses. PMID- 26368894 TI - Absolute thickness metrology with submicrometer accuracy using a low-coherence distance measuring interferometer. AB - Absolute physical thickness across the sample aperture is critical in determining the index of a refraction profile from the optical path length profile for gradient index (GRIN) materials, which have a designed inhomogeneous refractive index. Motivated by this application, instrumentation was established to measure the absolute thickness of samples with nominally plane-parallel surfaces up to 50 mm thick. The current system is capable of measuring absolute thickness with 120 nm (1sigma) repeatability and submicrometer expanded measurement uncertainty. Beside GRIN materials, this method is also capable of measuring other inhomogeneous and opaque materials. PMID- 26368895 TI - Method of determining effects of heat-induced irregular refractive index on an optical system. AB - The effects of an irregular refractive index on optical performance are examined. A method was developed to express a lens's irregular refractive index distribution. An optical system and its mountings were modeled by a thermomechanical finite element (FE) program in the predicted operating temperature range, -45 degrees C-50 degrees C. FE outputs were elaborated using a MATLAB optimization routine; a nonlinear least squares algorithm was adopted to determine which gradient equation best fit each lens's refractive index distribution. The obtained gradient data were imported into Zemax for sequential ray-tracing analysis. The root mean square spot diameter, modulation transfer function, and diffraction ensquared energy were computed for an optical system under an irregular refractive index and under thermoelastic deformation. These properties are greatly reduced by the irregular refractive index effect, which is one-third to five-sevenths the size of the thermoelastic deformation effect. Thus, thermal analyses of optical systems should consider not only thermoelastic deformation but also refractive index irregularities caused by inhomogeneous temperature. PMID- 26368896 TI - Research on the technique of large-aperture off-axis parabolic surface processing using tri-station machine and its applicability. AB - In order to process large-aperture aspherical mirrors, we designed and constructed a tri-station machine processing center with a three station device, which bears vectored feed motion of up to 10 axes. Based on this processing center, an aspherical mirror-processing model is proposed, in which each station implements traversal processing of large-aperture aspherical mirrors using only two axes, while the stations are switchable, thus lowering cost and enhancing processing efficiency. The applicability of the tri-station machine is also analyzed. At the same time, a simple and efficient zero-calibration method for processing is proposed. To validate the processing model, using our processing center, we processed an off-axis parabolic SiC mirror with an aperture diameter of 1450 mm. The experimental results indicate that, with a one-step iterative process, the peak to valley (PV) and root mean square (RMS) of the mirror converged from 3.441 and 0.5203 MUm to 2.637 and 0.2962 MUm, respectively, where the RMS reduced by 43%. The validity and high accuracy of the model are thereby demonstrated. PMID- 26368897 TI - Accurate estimation of the backscattering coefficient by light scattering at two backward angles. AB - Backscattering coefficients are frequently estimated from light scattering at one backward angle multiplied by a conversion factor. We determined that the shapes of the volume scattering functions (VSFs), particularly for scattering angles larger than 170 degrees , cause significant variations in the conversion factor at 120 degrees . Our approach uses the ratio of scattering at 170 degrees and at 120 degrees , which is a good indicator of the shape differences of the VSFs for most oceanic waters and wavelengths in the visible range. The proposed method provides significant accuracy improvement in the determination of the backscattering coefficients with a prediction error of 3% of the mean. PMID- 26368898 TI - Simulation of a high-speed superimposed fiber Bragg gratings interrogation system. AB - This paper presents a simulation of high-speed nonuniform random sampling in a superimposed fiber Bragg gratings (SFBGs) interrogation system. The simulated Gauss SFBGs are used to generate a nonuniform sensing pulse train during each scanning cycle. Six different conditions that can cause nonuniform sampling are simulated, and a random sine-wave driving method to improve the driving speed is proposed. An 11.8 kHz dynamic strain is measured by generating an additive nonuniform randomly distributed 12 kHz optical sensing pulse train from a mean 2 kHz sinusoidal periodically changing scanning frequency and three SFBGs. Four conditions that can improve the sampling results are also simulated. PMID- 26368899 TI - Enabling focusing around the corner in multiple scattering media. AB - We report an alternative experimental setup to laterally focus light at an angle of 90 deg relative to turbid, multiple scattering media, using preprocessing wavefront shaping. We compare the measured image quality to one obtained in the usual configuration for focusing light through turbid media, where focusing occurs behind the scattering sample. We demonstrate that the depth of focus in the lateral configuration is of the same order of the usual transversal one because both setups are designed to operate in the deep Fresnel zone. This result shows that this novel, versatile lateral configuration allows for effectively focusing around corners through multiple scattering samples. PMID- 26368900 TI - Thermal effects in Yb:YAG single-crystal thin-rod amplifier. AB - This work presents a new design for the laser gain module based on a ytterbium doped yttrium aluminum garnet (Yb:YAG) single-crystal thin rod. Thermal effects (temperature, phase, and polarization distortion of laser radiation) and small signal gain are investigated both experimentally and theoretically. We then analyzed the influence of thermal effects and amplified spontaneous emission on the power scaling of the laser based on the gain module. A small signal gain as high as 3.3 per pass was experimentally achieved. PMID- 26368901 TI - Efficient and broadband wavelength conversion in a slot waveguide with the periodic structure altering the phase-mismatch. AB - High-efficiency wavelength conversion based on the quasi-phase-matching technique is proposed and simulated in a silicon slot waveguide. Due to the tight light confinement and high nonlinear material (silicon nanocrystal) filled in the slot region, a large nonlinear coefficient of 4100/(W.m) is achieved. With the waveguide width changing alternately to manage the phase-mismatch, periodical attenuation of the idler power is suppressed even in the presence of severe dispersion. Numerical simulation shows that an efficiency of -12.3 dB at 1850 nm and a 3-dB bandwidth of 484 nm are available for the 1550 nm wavelength pump in a 4 mm long silicon slot waveguide. PMID- 26368902 TI - Method for targetless tracking subpixel in-plane movements. AB - We present a targetless motion tracking method for detecting planar movements with subpixel accuracy. This method is based on the computation and tracking of the intersection of two nonparallel straight-line segments in the image of a moving object in a scene. The method is simple and easy to implement because no complex structures have to be detected. It has been tested and validated using a lab experiment consisting of a vibrating object that was recorded with a high speed camera working at 1000 fps. We managed to track displacements with an accuracy of hundredths of pixel or even of thousandths of pixel in the case of tracking harmonic vibrations. The method is widely applicable because it can be used for distance measuring amplitude and frequency of vibrations with a vision system. PMID- 26368903 TI - Blackening of magnesium alloy using femtosecond laser. AB - Magnesium alloy, a potential structural and biodegradable material, has been increasingly attracting attention. In this paper, two structures with enhanced light absorption on an AZ31B magnesium surface are fabricated by femtosecond laser texturing. Laser power and the number of laser pulses are mainly investigated for darkening effect. After irradiation, surface characteristics are analyzed by a scanning electron microscope equipped with an energy dispersive spectrometer and laser scanning confocal microscope. The darkening effect is investigated by a spectrophotometer with an integrating sphere. Microgroove and stripe structures are obtained, which are covered with homogeneous nanoprotrusions and nanoparticles. The main surface chemical composition after laser ablation is MgO. The optimal light absorption in the visible range (wavelength of 400-800 nm) reaches about 98%, which is significantly improved compared with the untreated surface. The enhanced light absorption is mainly attributed to surface structure. Femtosecond laser surface texturing technology offers potential in the application of stealth technology, airborne devices, and biomedicine. PMID- 26368904 TI - Simultaneous 3D location and size measurement of bubbles and sand particles in a flow using interferometric particle imaging. AB - We present a system to characterize a triphasic flow in a 3D volume (air bubbles and solid irregular particles in water) using only one CCD sensor. A cylindrical interferometric out-of-focus imaging setup is used to determine simultaneously the 3D position and the size of bubbles and irregular sand particles in a flow. The 3D position of the particles is deduced from the ellipticity of their out-of focus image. The size of bubbles is deduced from analysis of interference fringes. The characteristics of irregular sand particles are obtained from analysis of their speckle-like pattern. Experiments are confirmed by simulations. PMID- 26368905 TI - Comprehensive study of unexpected microscope condensers formed in sample arrangements commonly used in optical microscopy. AB - We show that various setups for optical microscopy which are commonly used in biomedical laboratories behave like efficient microscope condensers that are responsible for observed subwavelength resolution. We present a series of experiments and simulations that reveal how inclined illumination from such unexpected condensers occurs when the sample is perpendicularly illuminated by a microscope's built-in white-light source. In addition, we demonstrate an inexpensive add-on optical module that serves as an efficient and lightweight microscope condenser. Using such add-on optical module in combination with a low numerical-aperture objective lens and Fourier plane imaging microscopy technique, we demonstrate detection of photonic crystals with a period nearly eight times smaller than the Rayleigh resolution limit. PMID- 26368906 TI - Camera self-calibration from translation by referring to a known camera. AB - This paper presents a novel linear method for camera self-calibration by referring to a known (or calibrated) camera. The method requires at least three images, with two images generated by the uncalibrated camera from pure translation and one image generated by the known reference camera. We first propose a method to compute the infinite homography from scene depths. Based on this, we use two images generated by translating the uncalibrated camera to recover scene depths, which are further utilized to linearly compute the infinite homography between an arbitrary uncalibrated image, and the image from the known camera. With the known camera as reference, the computed infinite homography is readily decomposed for camera calibration. The proposed self-calibration method has been tested with simulation and real image data. Experimental results demonstrate that the method is practical and accurate. This paper proposes using a "known reference camera" for camera calibration. The pure translation, as required in the method, is much more maneuverable, compared with some strict motions in the literature, such as pure rotation. The proposed self-calibration method has good potential for solving online camera calibration problems, which has important applications, especially for multicamera and zooming camera systems. PMID- 26368907 TI - Nonlinear dynamic phase response calibration by digital holographic microscopy. AB - An accurate phase characterization method by digital holographic microscopy for spatial light modulators (SLMs) is proposed. This method permits high precision measurement for individual SLM pixels. Based on this method, the nonlinear dynamic phase response of the SLM is analyzed and calibrated in two steps: the global phase calibration and the local phase calibration. After the calibrations, both the phase modulation deficiency and the sharp phase jump of the 26-step grating are optimized. The root mean square error of the phase grating is reduced from 1.6319 to 0.2132 rad. The accurate phase distribution control may find various applications concerning high-resolution and high-accuracy wavefront modulation. PMID- 26368908 TI - Quantitative analysis of chromium in potatoes by laser-induced breakdown spectroscopy coupled with linear multivariate calibration. AB - Laser-induced breakdown spectroscopy (LIBS) coupled with the linear multivariate regression method was utilized to analyze chromium (Cr) quantitatively in potatoes. The plasma was generated using a Nd:YAG laser, and the spectra were acquired by an Andor spectrometer integrated with an ICCD detector. The models between intensity of LIBS characteristic line(s) and concentration of Cr were constructed to predict quantitatively the content of target. The unary, binary, ternary, and quaternary variables were chosen for verifying the accuracy of linear regression calibration curves. The intensity of characteristic lines Cr (CrI: 425.43, 427.48, 428.97 nm) and Ca (CaI: 422.67, 428.30, 430.25, 430.77, 431.86 nm) were used as input data for the multivariate calculations. According to the results of linear regression, the model of quaternary linear regression was established better in comparing with the other three models. A good agreement was observed between the actual content provided by atomic absorption spectrometry and the predicted value obtained by the quaternary linear regression model. And the relative error was below 5.5% for validation samples S1 and S2. The result showed that the multivariate approach can obtain better predicted accuracy than the univariate ones. The result also suggested that the LIBS technique coupled with the linear multivariate calibration method could be a great tool to predict heavy metals in farm products in a rapid manner even though samples have similar elemental compositions. PMID- 26368909 TI - Optical encryption/decryption of 8PSK signal using FWM-based modified XOR. AB - A scheme for optical encryption/decryption of an eight-phase-shift keying (8PSK) signal is proposed, and this scheme applies modified optical XOR gates based on four-wave mixing (FWM) in a semiconductor optical amplifier (SOA). Theoretical analyses and simulations are conducted. Both the performance and the parameter design of a 40-Gbit/s all-optical encryption/decryption system under various key parameters are studied. The results are useful for designing optical encryption/decryption for complex modulated signals. PMID- 26368910 TI - Integrated Photonics Institute for Manufacturing Innovation: editorial. AB - Editor-in-Chief Ron Driggers discusses the founding of the Integrated Photonics Manufacturing Initiative. PMID- 26368911 TI - The Glass Half Empty: How Emotional Exhaustion Affects the State-Trait Discrepancy in Self-Reports of Teaching Emotions. AB - Following from previous research on intensity bias and the accessibility model of emotional self-report, the present study examined the role of emotional exhaustion in explaining the discrepancy in teachers' reports of their trait (habitual) versus state (momentary, "real") emotions. Trait reports (habitual emotions, exhaustion) were assessed via trait questionnaires, and state reports (momentary emotions) were assessed in real time via the experience sampling method by using personal digital assistants (N = 69 high school teachers; 1,089 measures within teachers). In line with our assumptions, multi-level analyses showed that, as compared to the state assessment, teachers reported higher levels of habitual teaching-related emotions of anger, anxiety, shame, boredom, enjoyment, and pride. Additionally, the state-trait discrepancy in self-reports of negative emotions was accounted for by teachers' emotional exhaustion, with high exhaustion levels corresponding with a greater state-trait discrepancy. Exhaustion levels did not moderate the state-trait discrepancy in positive emotions indicating that perceived emotional exhaustion may reflect identity related cognitions specific to the negative belief system. Implications for research and educational practice are discussed. PMID- 26368912 TI - Analyses of Large Data Bases and Pragmatic Clinical Trials: Advancing Comparative Effectiveness Research in a Learning Health Care System. PMID- 26368913 TI - Optimal Criteria Survey for Preresuscitation Delivery Room Checklists. AB - OBJECTIVE: To investigate the optimal format and content of delivery room reminder tools, such as checklists. STUDY DESIGN: Voluntary, anonymous web-based surveys on checklists and reminder tools for neonatal resuscitation were sent to clinicians at participating hospitals. Summary statistics including the mean and standard deviation of the survey items were calculated. Several key comparisons between groups were completed using Student t-test. RESULTS: Fifteen hospitals were surveyed and 299 responses were collected. Almost all (96%) respondents favored some form of a reminder tool. Specific reminders such as "check and prepare all equipment" (mean 3.69, SD 0.81) were ranked higher than general reminders and personnel reminders such as "introduction and assigning roles" (mean 3.23, SD 1.08). Rankings varied by profession, institution, and deliveries attended per month. CONCLUSIONS: Clinicians perceive a benefit of a checklist for neonatal resuscitation in the delivery room. Preparation of equipment was perceived as the most important use for checklists. PMID- 26368914 TI - Placental alpha-Microglobulin-1 in Vaginal Secretions of Women with Evidence of Preterm Labor. AB - OBJECTIVE: To evaluate the presence of placental alpha-microglobulin-1 (PAMG-1) in vaginal secretions in women with symptoms of preterm labor and assess its use as a predictor of preterm birth. STUDY DESIGN: A prospective cohort study of women between 16 and 34 weeks of gestation with symptoms of preterm labor and intact membranes was conducted. The presence of PAMG-1 was determined using a commercially available kit (AmniSure, AmniSure International LLC, Boston, MA). RESULTS: A total of 100 women were enrolled, of which 86 had outcome data available. PAMG-1 was detected in 19/86 (22.1%) subjects. These women were more likely to deliver within 7 days than those without PAMG-1 detected (6/19 [31.6%] vs. 5/67 [7.5%]; odds ratio 5.6; 95% confidence interval 1.5-21.6). These findings persisted after adjusting for potential confounders. The sensitivity was 54.6%, specificity was 82.7%, positive predictive value was 31.6%, and the negative predictive was 92.5%. CONCLUSION: The presence of PAMG-1 is associated with an increased likelihood of delivery within 7 days. PMID- 26368915 TI - Examining the Starting Dose of Glyburide in Gestational Diabetes. AB - OBJECTIVE: The aim of this study was to determine the impact of initial glyburide dosing on pregnancy outcomes. STUDY DESign: Retrospective cohort of singleton pregnancies complicated by gestational diabetes mellitus (GDM) from 2007 to 2013. Women who received glyburide were compared by initial dose: 2.5 mg (n = 170) versus 5 mg (n = 154) total daily dose. The primary maternal outcome was hypoglycemia, defined as a blood glucose < 60 mg/dL. The primary neonatal outcome was birth weight. Secondary maternal outcomes included time to blood glucose control, preeclampsia, and cesarean delivery. Secondary neonatal outcomes included macrosomia (>4,000 g), hypoglycemia (<40 mg/dL), shoulder dystocia, and preterm delivery. RESULTS: The 5 mg/day glyburide dose did not increase maternal hypoglycemia (26% in the 2.5 mg/day group vs. 27% in the 5 mg/day group; adjusted odds ratio [AOR] 0.67; confidence interval [CI] 0.30-1.49). An increase in macrosomia in the 5 mg/day group was not significant after adjusting for maternal obesity (AOR 2.16; CI 0.96-4.88). Differences in preterm birth and large for gestational age were not significant after adjusting for prior preterm birth and maternal obesity, respectively. CONCLUSIONS: A higher starting dose of glyburide for the management of GDM was not associated with increased maternal hypoglycemia or decreased adverse neonatal outcomes. PMID- 26368916 TI - Lithium Bromide/Water as Additives in Dearomatizing Samarium-Ketyl (Hetero)Arene Cyclizations. AB - New conditions for dearomatizing samarium-ketyl (hetero)arene cyclizations are reported. In many examples of these samarium diiodide-mediated reactions, lithium bromide and water can be used as additives instead of the carcinogenic and mutagenic hexamethylphosphoramide (HMPA). The best results were obtained for the cyclizations of N-acylated indole derivatives delivering the expected indolines in good yields and excellent diastereoselectivities. A new type of cyclization delivering indolyl-substituted allene derivatives is also described. The scope and limitations of the lithium bromide/water system are discussed. PMID- 26368917 TI - Beyond Corroboration: Strengthening Model Validation by Looking for Unexpected Patterns. AB - Models of emergent phenomena are designed to provide an explanation to global scale phenomena from local-scale processes. Model validation is commonly done by verifying that the model is able to reproduce the patterns to be explained. We argue that robust validation must not only be based on corroboration, but also on attempting to falsify the model, i.e. making sure that the model behaves soundly for any reasonable input and parameter values. We propose an open-ended evolutionary method based on Novelty Search to look for the diverse patterns a model can produce. The Pattern Space Exploration method was tested on a model of collective motion and compared to three common a priori sampling experiment designs. The method successfully discovered all known qualitatively different kinds of collective motion, and performed much better than the a priori sampling methods. The method was then applied to a case study of city system dynamics to explore the model's predicted values of city hierarchisation and population growth. This case study showed that the method can provide insights on potential predictive scenarios as well as falsifiers of the model when the simulated dynamics are highly unrealistic. PMID- 26368918 TI - Targeting Leukocyte Trafficking in Inflammatory Bowel Disease: What Is the Clinical Evidence? AB - Since the cause of inflammatory bowel disease (IBD) is unknown, therapy has traditionally been based on the empiric use of anti-inflammatory drugs. However, the recent identification of specific mechanisms that regulate cellular migration into inflamed intestinal tissue has provided novel targets for drug development. In this article, we discuss these mechanisms and review emerging safety and efficacy data regarding use of selective inhibitors of leukocyte trafficking for the treatment of IBD. PMID- 26368919 TI - Macroecology of Australian Tall Eucalypt Forests: Baseline Data from a Continental-Scale Permanent Plot Network. AB - Tracking the response of forest ecosystems to climate change demands large (>=1 ha) monitoring plots that are repeatedly measured over long time frames and arranged across macro-ecological gradients. Continental scale networks of permanent forest plots have identified links between climate and carbon fluxes by monitoring trends in tree growth, mortality and recruitment. The relationship between tree growth and climate in Australia has been recently articulated through analysis of data from smaller forest plots, but conclusions were limited by (a) absence of data on recruitment and mortality, (b) exclusion of non eucalypt species, and (c) lack of knowledge of stand age or disturbance histories. To remedy these gaps we established the Ausplots Forest Monitoring Network: a continental scale network of 48 1 ha permanent plots in highly productive tall eucalypt forests in the mature growth stage. These plots are distributed across cool temperate, Mediterranean, subtropical and tropical climates (mean annual precipitation 850 to 1900 mm per year; mean annual temperature 6 to 21 degrees C). Aboveground carbon stocks (AGC) in these forests are dominated by eucalypts (90% of AGC) whilst non-eucalypts in the understorey dominated species diversity and tree abundance (84% of species; 60% of stems). Aboveground carbon stocks were negatively related to mean annual temperature, with forests at the warm end of the temperature range storing approximately half the amount of carbon as forests at the cool end of the temperature range. This may reflect thermal constraints on tree growth detected through other plot networks and physiological studies. Through common protocols and careful sampling design, the Ausplots Forest Monitoring Network will facilitate the integration of tall eucalypt forests into established global forest monitoring initiatives. In the context of projections of rapidly warming and drying climates in Australia, this plot network will enable detection of links between climate and growth, mortality and carbon dynamics of eucalypt forests. PMID- 26368920 TI - Quantitative Lesion-to-Fat Elasticity Ratio Measured by Shear-Wave Elastography for Breast Mass: Which Area Should Be Selected as the Fat Reference? AB - OBJECTIVES: To investigate whether the diagnostic performance of lesion-to-fat elasticity ratio (Eratio) was affected by the location of the reference fat. METHODS: For 257 breast masses in 250 women who underwent shear-wave elastography before biopsy or surgery, multiple Eratios were measured with a fixed region-of interest (ROI) in the mass along with multiple ROIs over the surrounding fat in different locations. Logistic regression analysis was used to determine that Eratio was independently associated with malignancy adjusted for the location of fat ROI (depth, laterality, and distance from lesion or skin). Mean (Emean) and maximum (Emax) elasticity values of fat were divided into four groups according to their interquartile ranges. Diagnostic performance of each group was evaluated using the area under the ROC curve (AUC). False diagnoses of Eratio were reviewed for ROIs on areas showing artifactual high or low stiffness and analyzed by logistic regression analysis to determine variables (associated palpable abnormality, lesion size, the vertical distance from fat ROI to skin, and elasticity values of lesion or fat) independently associated with false results. RESULTS: Eratio was independently associated with malignancy adjusted for the location of fat ROI (P<0.0001). Among four groups of fat elasticity values, the AUC showed no significant difference (<25th percentile, 25th percentile~median, median~75th percentile, and >=75th percentile; 0.973, 0.982, 0.967, and 0.954 for Emean; 0.977, 0.967, 0.966, and 0.957 for Emax). Fat elasticity values were independently associated with false results of Eratio with the cut-off of 3.18 from ROC curve (P<0.0001). ROIs were set on fat showing artifactual high stiffness in 90% of 10 false negatives and on lesion showing vertical striped artifact or fat showing artifactual low stiffness in 77.5% of 71 false positives. CONCLUSION: Eratio shows good diagnostic performance regardless of the location of reference fat, except when it is placed in areas of artifacts. PMID- 26368921 TI - Treatment as Required versus Regular Monthly Treatment in the Management of Neovascular Age-Related Macular Degeneration: A Systematic Review and Meta Analysis. AB - BACKGROUND: To investigate whether treatment as required 'pro re nata' (PRN) versus regular monthly treatment regimens lead to differences in outcomes in neovascular age-related macular degeneration (nAMD). Regular monthly administration of vascular endothelial growth factor (VEGF) inhibitors is an established gold standard treatment, but this approach is costly. Replacement of monthly by PRN treatment can only be justified if there is no difference in patient relevant outcomes. METHODS: Systematic review and meta-analysis. The intervention was PRN treatment and the comparator was monthly treatment with VEGF inhibitors. Four bibliographic databases were searched for randomised controlled trials comparing both treatment regimens directly (head-to-head studies). The last literature search was conducted in December 2014. Risk of bias assessment was performed after the Cochrane Handbook for Systematic Reviews of Interventions. FINDINGS: We included 3 head-to-head studies (6 reports) involving more than 2000 patients. After 2 years, the weighted mean difference in best corrected visual acuity (BCVA) was 1.9 (95% CI 0.5 to 3.3) ETDRS letters in favour of monthly treatment. Systemic adverse events were higher in PRN treated patients, but these differences were not statistically significant. After 2 years, the total number of intravitreal injections required by the patients in the PRN arms were 8.4 (95% CI 7.9 to 8.9) fewer than those having monthly treatment. The studies were considered to have a moderate risk of bias. CONCLUSIONS: PRN treatment resulted in minor but statistically significant decrease in mean BCVA which may not be clinically meaningful. There is a small increase in risk of systemic adverse events for PRN treated patients. Overall, the results indicate that an individualized treatment approach with anti-VEGF using visual acuity and OCT-guided re-treatment criteria may be appropriate for most patients with nAMD. PMID- 26368922 TI - Protein Folding Mechanism of the Dimeric AmphiphysinII/Bin1 N-BAR Domain. AB - The human AmphyphisinII/Bin1 N-BAR domain belongs to the BAR domain superfamily, whose members sense and generate membrane curvatures. The N-BAR domain is a 57 kDa homodimeric protein comprising a six helix bundle. Here we report the protein folding mechanism of this protein as a representative of this protein superfamily. The concentration dependent thermodynamic stability was studied by urea equilibrium transition curves followed by fluorescence and far-UV CD spectroscopy. Kinetic unfolding and refolding experiments, including rapid double and triple mixing techniques, allowed to unravel the complex folding behavior of N-BAR. The equilibrium unfolding transition curve can be described by a two-state process, while the folding kinetics show four refolding phases, an additional burst reaction and two unfolding phases. All fast refolding phases show a rollover in the chevron plot but only one of these phases depends on the protein concentration reporting the dimerization step. Secondary structure formation occurs during the three fast refolding phases. The slowest phase can be assigned to a proline isomerization. All kinetic experiments were also followed by fluorescence anisotropy detection to verify the assignment of the dimerization step to the respective folding phase. Based on these experiments we propose for N BAR two parallel folding pathways towards the homodimeric native state depending on the proline conformation in the unfolded state. PMID- 26368923 TI - Spatial Habitat Features Derived from Multiparametric Magnetic Resonance Imaging Data Are Associated with Molecular Subtype and 12-Month Survival Status in Glioblastoma Multiforme. AB - One of the most common and aggressive malignant brain tumors is Glioblastoma multiforme. Despite the multimodality treatment such as radiation therapy and chemotherapy (temozolomide: TMZ), the median survival rate of glioblastoma patient is less than 15 months. In this study, we investigated the association between measures of spatial diversity derived from spatial point pattern analysis of multiparametric magnetic resonance imaging (MRI) data with molecular status as well as 12-month survival in glioblastoma. We obtained 27 measures of spatial proximity (diversity) via spatial point pattern analysis of multiparametric T1 post-contrast and T2 fluid-attenuated inversion recovery MRI data. These measures were used to predict 12-month survival status (<=12 or >12 months) in 74 glioblastoma patients. Kaplan-Meier with receiver operating characteristic analyses was used to assess the relationship between derived spatial features and 12-month survival status as well as molecular subtype status in patients with glioblastoma. Kaplan-Meier survival analysis revealed that 14 spatial features were capable of stratifying overall survival in a statistically significant manner. For prediction of 12-month survival status based on these diversity indices, sensitivity and specificity were 0.86 and 0.64, respectively. The area under the receiver operating characteristic curve and the accuracy were 0.76 and 0.75, respectively. For prediction of molecular subtype status, proneural subtype shows highest accuracy of 0.93 among all molecular subtypes based on receiver operating characteristic analysis. We find that measures of spatial diversity from point pattern analysis of intensity habitats from T1 post-contrast and T2 fluid-attenuated inversion recovery images are associated with both tumor subtype status and 12-month survival status and may therefore be useful indicators of patient prognosis, in addition to providing potential guidance for molecularly targeted therapies in Glioblastoma multiforme. PMID- 26368924 TI - Artificial Intelligence versus Statistical Modeling and Optimization of Cholesterol Oxidase Production by using Streptomyces Sp. AB - Cholesterol oxidase (COD) is a bi-functional FAD-containing oxidoreductase which catalyzes the oxidation of cholesterol into 4-cholesten-3-one. The wider biological functions and clinical applications of COD have urged the screening, isolation and characterization of newer microbes from diverse habitats as a source of COD and optimization and over-production of COD for various uses. The practicability of statistical/ artificial intelligence techniques, such as response surface methodology (RSM), artificial neural network (ANN) and genetic algorithm (GA) have been tested to optimize the medium composition for the production of COD from novel strain Streptomyces sp. NCIM 5500. All experiments were performed according to the five factor central composite design (CCD) and the generated data was analysed using RSM and ANN. GA was employed to optimize the models generated by RSM and ANN. Based upon the predicted COD concentration, the model developed with ANN was found to be superior to the model developed with RSM. The RSM-GA approach predicted maximum of 6.283 U/mL COD production, whereas the ANN-GA approach predicted a maximum of 9.93 U/mL COD concentration. The optimum concentrations of the medium variables predicted through ANN-GA approach were: 1.431 g/50 mL soybean, 1.389 g/50 mL maltose, 0.029 g/50 mL MgSO4, 0.45 g/50 mL NaCl and 2.235 ml/50 mL glycerol. The experimental COD concentration was concurrent with the GA predicted yield and led to 9.75 U/mL COD production, which was nearly two times higher than the yield (4.2 U/mL) obtained with the un optimized medium. This is the very first time we are reporting the statistical versus artificial intelligence based modeling and optimization of COD production by Streptomyces sp. NCIM 5500. PMID- 26368925 TI - Utility of Functional Hemodynamics and Echocardiography to Aid Diagnosis and Management of Shock. AB - The utility of functional hemodynamics and bedside ultrasonography is increasingly recognized as advantageous for both improved diagnosis and management of shock states. In contrast to conventional "static" measures, "dynamic" hemodynamic measures and bedside imaging modalities enhance pathophysiology-based comprehensive understanding of shock states and the response to therapy. The current editions of major textbooks in the primary specialties--in which clinicians routinely encounter patients in shock--including surgery, anesthesia, emergency medicine, and internal medicine continue to incorporate traditional (conventional) descriptions of shock that use well described (but potentially misleading) intravascular pressures to classify shock states. Reliance on such intravascular pressure measurements is not as helpful as newer "dynamic" functional measures including ultrasonography to both better assess volume responsiveness and biventricular cardiac function. This review thus emphasizes the application of current functional hemodynamics and ultrasonography to the diagnosis and management of shock as a contrast to conventional "static" pressure-based measures. PMID- 26368926 TI - The Effects of Alcohol Intoxication and Burn Injury on the Expression of Claudins and Mucins in the Small and Large Intestines. AB - Alcohol intoxication at the time of burn injury exacerbates postburn pathogenesis. Recent findings suggest gut barrier integrity is compromised after combined alcohol and burn insult, which could contribute to these complications. Tight junction proteins and mucins play critical roles in keeping the gut barrier intact. Therefore, the goal of this study was to examine the effects of alcohol and burn injury on claudin and mucin expression in the intestines. We also evaluated if the combined insult differentially influences their expression in the small and large intestines. Male C57BL/6 mice were given a single dose of 2.9 g/kg ethanol before an approximately 12.5% body area burn. One and three days after injury, we profiled expression of several tight junction proteins, mucin, and bacterial 16S rRNA genes in the small and large intestines, using qPCR. We observed >50% decrease in claudin-4 and claudin-8 genes in both ileal and colonic epithelial cells 1 day after injury. Claudin-2 was significantly upregulated, and occludin was downregulated in the small intestine 1 day after injury. Mucin-3 expression was substantially elevated (>50%) in the small intestine, whereas mucin-2 and mucin-4 were considerably diminished in the colon (>50%) 1 day after injury. Most of the parameters were normalized to sham levels on day 3, except for mucin-3 and claudin-8, which remained decreased in the large intestine. Neither alcohol nor burn alone resulted in changes in junction or mucin gene expression compared to shams. This was accompanied with increases in the family of Gram-negative bacteria, Enterobacteriaceae, in both the small and the large intestines 1 day after injury. These findings suggest that alcohol and burn injury disrupts the normal gut microbiota and alters tight junction and mucin expression in the small and large intestines. PMID- 26368927 TI - Evaluation of the CytosorbTM Hemoadsorptive Column in a Pig Model of Severe Smoke and Burn Injury. AB - INTRODUCTION: Host inflammatory response to any form of tissue injury, including burn, trauma, or shock, has been well documented. After significant burns, cytokines can increase substantially within the first 24 h after injury and may contribute to subsequent organ failure. Hemoadsorption by cytokine-adsorbing columns may attenuate this maladaptive response, thereby improving outcomes. The aim of this study was to investigate the feasibility, technical safety, and efficacy of cytokine and myoglobin removal by early use of a cytokine absorbing column (CytoSorb) in a porcine model of smoke inhalation and burn injury. METHODS: Anesthetized female Yorkshire pigs (n = 15) were injured by wood bark smoke inhalation and a 40% total body surface area deep burn and observed for 72 h or death. The animals were randomized to hemoadsorption treatment (n = 9) or a sham group (n = 6) before injury. A 6-h hemoadsorption or sham session was performed on days one, two, and three. Serum cytokines (IL-1b, IL-6, IL-8, IL-10, TNF-alpha) and myoglobin were measured systemically, locally in bronchoalveolar lavage fluid and also in circulating blood before and after the adsorbing column to evaluate single pass clearance by the device. RESULTS: Hemoadsorption caused significant removal of IL-1b, IL-6, IL-10, and myoglobin across the device mainly during the first run, ranging from 22% for IL-6 to 29% for IL-1b and 41% removal rates for myoglobin after 15 min of treatment. Systemic cytokine or myoglobin serum concentrations did not change. CONCLUSIONS: In a porcine model of smoke and burn injury, hemoadsorption using the CytoSorb cartridge did not result in significant systemic or pulmonary reductions in the measured cytokines or myoglobin despite efficient transmembrane reductions. Further investigations are needed to optimize the efficiency of mediator clearance to affect both circulating levels and clinically relevant outcomes. PMID- 26368929 TI - The Volatility of Data Space: Topology Oriented Sensitivity Analysis. AB - Despite the difference among specific methods, existing Sensitivity Analysis (SA) technologies are all value-based, that is, the uncertainties in the model input and output are quantified as changes of values. This paradigm provides only limited insight into the nature of models and the modeled systems. In addition to the value of data, a potentially richer information about the model lies in the topological difference between pre-model data space and post-model data space. This paper introduces an innovative SA method called Topology Oriented Sensitivity Analysis, which defines sensitivity as the volatility of data space. It extends SA into a deeper level that lies in the topology of data. PMID- 26368928 TI - A Naturally Occurring Canine Model of Autosomal Recessive Congenital Stationary Night Blindness. AB - Congenital stationary night blindness (CSNB) is a non-progressive, clinically and genetically heterogeneous disease of impaired night vision. We report a naturally occurring, stationary, autosomal recessive phenotype in beagle dogs with normal daylight vision but absent night vision. Affected dogs had normal retinas on clinical examination, but showed no detectable rod responses. They had "negative type" mixed rod and cone responses in full-field ERGs. Their photopic long-flash ERGs had normal OFF-responses associated with severely reduced ON-responses. The phenotype is similar to the Schubert-Bornschein form of complete CSNB in humans. Homozygosity mapping ruled out most known CSNB candidates as well as CACNA2D4 and GNB3. Three remaining genes were excluded based on sequencing the open reading frame and intron-exon boundaries (RHO, NYX), causal to a different form of CSNB (RHO) or X-chromosome (NYX, CACNA1F) location. Among the genes expressed in the photoreceptors and their synaptic terminals, and mGluR6 cascade and modulators, reduced expression of GNAT1, CACNA2D4 and NYX was observed by qRT-PCR in both carrier (n = 2) and affected (n = 2) retinas whereas CACNA1F was down-regulated only in the affecteds. Retinal morphology revealed normal cellular layers and structure, and electron microscopy showed normal rod spherules and synaptic ribbons. No difference from normal was observed by immunohistochemistry (IHC) for antibodies labeling rods, cones and their presynaptic terminals. None of the retinas showed any sign of stress. Selected proteins of mGluR6 cascade and its modulators were examined by IHC and showed that PKCalpha weakly labeled the rod bipolar somata in the affected, but intensely labeled axonal terminals that appeared thickened and irregular. Dendritic terminals of ON-bipolar cells showed increased Goalpha labeling. Both PKCalpha and Goalpha labeled the more prominent bipolar dendrites that extended into the OPL in affected but not normal retinas. Interestingly, RGS11 showed no labeling in the affected retina. Our results indicate involvement of a yet unknown gene in this canine model of complete CSNB. PMID- 26368931 TI - Correction: Avian Reovirus Protein p17 Functions as a Nucleoporin Tpr Suppressor Leading to Activation of p53, p21 and PTEN and Inactivation of PI3K/AKT/mTOR and ERK Signaling Pathways. PMID- 26368930 TI - Interactions between Biliverdin, Oxidative Damage, and Spleen Morphology after Simulated Aggressive Encounters in Veiled Chameleons. AB - Stressors frequently increase oxidative damage--unless organisms simultaneously mount effective antioxidant responses. One putative mitigative mechanism is the use of biliverdin, an antioxidant produced in the spleen during erythrocyte degradation. We hypothesized that both wild and captive-bred male veiled chameleons (Chamaeleo calyptratus), which are highly aggressive to conspecifics, would respond to agonistic displays with increased levels of oxidative damage, but that increased levels of biliverdin would limit this increase. We found that even just visual exposure to a potential combatant resulted in decreased body mass during the subsequent 48-hour period, but that hematocrit, biliverdin concentration in the bile, relative spleen size, and oxidative damage in plasma, liver, and spleen were unaffected. Contrary to our predictions, we found that individuals with smaller spleens exhibited greater decreases in hematocrit and higher bile biliverdin concentrations, suggesting a revision to the idea of spleen-dependent erythrocyte processing. Interestingly, individuals with larger spleens had reduced oxidative damage in both the liver and spleen, demonstrating the spleen's importance in modulating oxidative damage. We also uncovered differences in spleen size and oxidative damage between wild and captive-bred chameleons, highlighting environmentally dependent differences in oxidative physiology. Lastly, we found no relationship between oxidative damage and biliverdin concentration, calling into question biliverdin's antioxidant role in this species. PMID- 26368932 TI - Correction: Iodide Protects Heart Tissue from Reperfusion Injury. PMID- 26368933 TI - Magnetoencephalography Reveals a Widespread Increase in Network Connectivity in Idiopathic/Genetic Generalized Epilepsy. AB - Idiopathic/genetic generalized epilepsy (IGE/GGE) is characterized by seizures, which start and rapidly engage widely distributed networks, and result in symptoms such as absences, generalized myoclonic and primary generalized tonic clonic seizures. Although routine magnetic resonance imaging is apparently normal, many studies have reported structural alterations in IGE/GGE patients using diffusion tensor imaging and voxel-based morphometry. Changes have also been reported in functional networks during generalized spike wave discharges. However, network function in the resting-state without epileptiforme discharges has been less well studied. We hypothesize that resting-state networks are more representative of the underlying pathophysiology and abnormal network synchrony. We studied functional network connectivity derived from whole-brain magnetoencephalography recordings in thirteen IGE/GGE and nineteen healthy controls. Using graph theoretical network analysis, we found a widespread increase in connectivity in patients compared to controls. These changes were most pronounced in the motor network, the mesio-frontal and temporal cortex. We did not, however, find any significant difference between the normalized clustering coefficients, indicating preserved gross network architecture. Our findings suggest that increased resting state connectivity could be an important factor for seizure spread and/or generation in IGE/GGE, and could serve as a biomarker for the disease. PMID- 26368934 TI - Which and How Many Patients Should Be Included in Randomised Controlled Trials to Demonstrate the Efficacy of Biologics in Primary Sjogren's Syndrome? AB - OBJECTIVE: The goal of this study was to determine how the choice of the primary endpoint influenced sample size estimates in randomised controlled trials (RCTs) of treatments for primary Sjogren's syndrome (pSS). METHODS: We reviewed all studies evaluating biotechnological therapies in pSS to identify their inclusion criteria and primary endpoints. Then, in a large cohort (ASSESS), we determined the proportion of patients who would be included in RCTs using various inclusion criteria sets. Finally, we used the population of a large randomised therapeutic trial in pSS (TEARS) to assess the impact of various primary objectives and endpoints on estimated sample sizes. These analyses were performed only for the endpoints indicating greater efficacy of rituximab compared to the placebo. RESULTS: We identified 18 studies. The most common inclusion criteria were short disease duration; systemic involvement; high mean visual analogue scale (VAS) scores for dryness, pain, and fatigue; and biological evidence of activity. In the ASSESS cohort, 35 percent of patients had recent-onset disease (lower than 4 years), 68 percent systemic manifestations, 68 percent high scores on two of three VASs, and 52 percent biological evidence of activity. The primary endpoints associated with the smallest sample sizes (nlower than 200) were a VAS dryness score improvement higher to 20 mm by week 24 or variable improvements (10, 20, or 30 mm) in fatigue VAS by week 6 or 16. For patients with systemic manifestations, the ESSDAI change may be the most logical endpoint, as it reflects all domains of disease activity. However, the ESSDAI did not improve significantly with rituximab therapy in the TEARS study. Ultrasound score improvement produced the smallest sample size estimate in the TEARS study. CONCLUSION: This study provides valuable information for designing future RCTs on the basis of previously published studies. Previous RCTs used inclusion criteria that selected a small part of the entire pSS population. The endpoint was usually based on VASs assessing patient complaints. In contrast to VAS dryness cut-offs, VAS fatigue cut-offs did not affect estimated sample sizes. SGUS improvement produced the smallest estimated sample size. Further studies are required to validate standardised SGUS modalities and assessment criteria. Thus, researchers should strive to develop a composite primary endpoint and to determine its best cut-off and assessment time point. PMID- 26368935 TI - Validation of Recombinant Salivary Protein PpSP32 as a Suitable Marker of Human Exposure to Phlebotomus papatasi, the Vector of Leishmania major in Tunisia. AB - BACKGROUND: During a blood meal, female sand flies, vectors of Leishmania parasites, inject saliva into the host skin. Sand fly saliva is composed of a large variety of components that exert different pharmacological activities facilitating the acquisition of blood by the insect. Importantly, proteins present in saliva are able to elicit the production of specific anti-saliva antibodies, which can be used as markers for exposure to vector bites. Serological tests using total sand fly salivary gland extracts are challenging due to the difficulty of obtaining reproducible salivary gland preparations. Previously, we demonstrated that PpSP32 is the immunodominant salivary antigen in humans exposed to Phlebotomus papatasi bites and established that humans exposed to P. perniciosus bites do not recognize it. METHODOLOGY/PRINCIPAL FINDINGS: Herein, we have validated, in a large cohort of 522 individuals, the use of the Phlebotomus papatasi recombinant salivary protein PpSP32 (rPpSP32) as an alternative method for testing exposure to the bite of this sand fly. We also demonstrated that screening for total anti-rPpSP32 IgG antibodies is sufficient, being comparable in efficacy to the screening for IgG2, IgG4 and IgE antibodies against rPpSP32. Additionally, sera obtained from dogs immunized with saliva of P. perniciosus, a sympatric and widely distributed sand fly in Tunisia, did not recognize rPpSP32 demonstrating its suitability as a marker of exposure to P. papatasi saliva. CONCLUSIONS/SIGNIFICANCE: Our data indicate that rPpSP32 constitutes a useful epidemiological tool to monitor the spatial distribution of P. papatasi in a particular region, to direct control measures against zoonotic cutaneous leishmaniasis, to assess the efficiency of vector control interventions and perhaps to assess the risk of contracting the disease. PMID- 26368936 TI - Relative Roles of Soil Moisture, Nutrient Supply, Depth, and Mechanical Impedance in Determining Composition and Structure of Wisconsin Prairies. AB - Ecologists have long classified Midwestern prairies based on compositional variation assumed to reflect local gradients in moisture availability. The best known classification is based on Curtis' continuum index (CI), calculated using the presence of indicator species thought centered on different portions of an underlying moisture gradient. Direct evidence of the extent to which CI reflects differences in moisture availability has been lacking, however. Many factors that increase moisture availability (e.g., soil depth, silt content) also increase nutrient supply and decrease soil mechanical impedance; the ecological effects of the last have rarely been considered in any ecosystem. Decreased soil mechanical impedance should increase the availability of soil moisture and nutrients by reducing the root costs of retrieving both. Here we assess the relative importance of soil moisture, nutrient supply, and mechanical impedance in determining prairie composition and structure. We used leaf delta13C of C3 plants as a measure of growing-season moisture availability, cation exchange capacity (CEC) x soil depth as a measure of mineral nutrient availability, and penetrometer data as a measure of soil mechanical impedance. Community composition and structure were assessed in 17 remnant prairies in Wisconsin which vary little in annual precipitation. Ordination and regression analyses showed that delta13C increased with CI toward "drier" sites, and decreased with soil depth and % silt content. Variation in delta13C among remnants was 2.00/00, comparable to that along continental gradients from ca. 500-1500 mm annual rainfall. As predicted, LAI and average leaf height increased significantly toward "wetter" sites. CI accounted for 54% of compositional variance but delta13C accounted for only 6.2%, despite the strong relationships of delta13C to CI and CI to composition. Compositional variation reflects soil fertility and mechanical impedance more than moisture availability. This study is the first to quantify the effects of soil mechanical impedance on community ecology. PMID- 26368937 TI - The Oral Microbiome of Denture Wearers Is Influenced by Levels of Natural Dentition. AB - OBJECTIVES: The composition of dental plaque has been well defined, whereas currently there is limited understanding of the composition of denture plaque and how it directly influences denture related stomatitis (DS). The aims of this study were to compare the microbiomes of denture wearers, and to understand the implications of these towards inter-kingdom and host-pathogen interactions within the oral cavity. METHODS: Swab samples were obtained from 123 participants wearing either a complete or partial denture; the bacterial composition of each sample was determined using bar-coded illumina MiSeq sequencing of the bacterial hypervariable V4 region of 16S rDNA. Sequencing data processing was undertaken using QIIME, clustered in Operational Taxonomic Units (OTUs) and assigned to taxonomy. The dentures were sonicated to remove the microbial flora residing on the prosthesis, sonicate was then cultured using diagnostic colorex Candida media. Samples of unstimulated saliva were obtained and antimicrobial peptides (AMP) levels were measured by ELISA. RESULTS: We have shown that dental and denture plaques are significantly distinct both in composition and diversity and that the oral microbiome composition of a denture wearer is variable and is influenced by the location within the mouth. Dentures and mucosa were predominantly made up of Bacilli and Actinobacteria. Moreover, the presence of natural teeth has a significant impact on the overall microbial composition, when compared to the fully edentulous. Furthermore, increasing levels of Candida spp. positively correlate with Lactobacillus spp. AMPs were quantified, though showed no specific correlations. CONCLUSIONS: This is the first study to provide a detailed understanding of the oral microbiome of denture wearers and has provided evidence that DS development is more complex than simply a candidal infection. Both fungal and bacterial kingdoms clearly play a role in defining the progression of DS, though we were unable to show a defined role for AMPs. PMID- 26368938 TI - Discrepancies in Outcome Reporting Exist Between Protocols and Published Oral Health Cochrane Systematic Reviews. AB - OBJECTIVES: To assess discrepancies in the analyzed outcomes between protocols and published reviews within Cochrane oral health systematic reviews (COHG) on the Cochrane Database of Systematic Reviews (CDSR). STUDY DESIGN AND SETTING: All COHG systematic reviews on the CDSR and the corresponding protocols were retrieved in November 2014 and information on the reported outcomes was recorded. Data was collected at the systematic review level by two reviewers independently. RESULTS: One hundred and fifty two reviews were included. In relation to primary outcomes, 11.2% were downgraded to secondary outcomes, 9.9% were omitted altogether in the final publication and new primary outcomes were identified in 18.4% of publications. For secondary outcomes, 2% were upgraded to primary, 12.5% were omitted and 30.9% were newly introduced in the publication. Overall, 45.4% of reviews had at least one discrepancy when compared to the protocol; these were reported in 14.5% reviews. The number of review updates appears to be associated with discrepancies between final review and protocol (OR: 3.18, 95% CI: 1.77, 5.74, p<0.001). The risk of reporting significant results was lower for both downgraded outcomes [RR: 0.52, 95% CI: 0.17, 1.58, p = 0.24] and upgraded or newly introduced outcomes [RR: 0.77, 95% CI: 0.36, 1.64, p = 0.50] compared to outcomes with no discrepancies. The risk of reporting significant results was higher for upgraded or newly introduced outcomes compared to downgraded outcomes (RR = 1.19, 95% CI: 0.65, 2.16, p = 0.57). None of the comparisons reached statistical significance. CONCLUSION: While no evidence of selective outcome reporting was found in this study, based on the present analysis of SRs published within COHG systematic reviews, discrepancies between outcomes in pre-published protocols and final reviews continue to be common. Solutions such as the use of standardized outcomes to reduce the prevalence of this issue may need to be explored. PMID- 26368940 TI - miR-182 (microRNA-182) suppression in the hippocampus evokes antidepressant-like effects in rats. AB - Depression is a serious and potentially life-threatening mental disorder with unknown etiology. Emerging evidence shows that brain-derived neurotrophic factor (BDNF) and microRNAs (miRNAs) play critical roles in the etiology of depression. However, the molecular mechanisms are not fully understood. Expression of miR-182 and BDNF in the hippocampus were analyzed in a chronic unpredictable mild stress (CUMS) model. Male Wistar rats received bilateral intra-hippocampal infusions of BDNF- and miR-182-expressing (miR-182) or miR-182-silencers (si-miR-182) lentiviral vectors (LV). miR-182 upregulation was correlated with decreased BDNF expression in the hippocampus of a CUMS model. Accordingly, an anti-depressant like effect was observed when LV-BDNF or LV-si-miR-182 was injected into the hippocampus. Moreover, BDNF and its target gene cyclic AMP responsive element binding protein 1 (CREB1) decreased following LV-miR-182 injection and increased upon LV-si-miR-182 injection in rat hippocampus and cultured neuronal cells. In contrast, miR-182 overexpression exacerbated depression-like behaviors and decreased BDNF. Further, luciferase reporter evidence confirmed BDNF was a miR 182 target. Taken together, the current results reveal a potential molecular regulation of miR-182 on BDNF and the pronounced behavioral consequences of this regulation. PMID- 26368939 TI - Effect of Calcifications on Breast Ultrasound Shear Wave Elastography: An Investigational Study. AB - PURPOSE: To investigate the effects of macrocalcifications and clustered microcalcifications associated with benign breast masses on shear wave elastography (SWE). METHODS: SuperSonic Imagine (SSI) and comb-push ultrasound shear elastography (CUSE) were performed on three sets of phantoms to investigate how calcifications of different sizes and distributions influence measured elasticity. To demonstrate the effect in vivo, three female patients with benign breast masses associated with mammographically-identified calcifications were evaluated by CUSE. RESULTS: Apparent maximum elasticity (Emax) estimates resulting from individual macrocalcifications (with diameters of 2mm, 3mm, 5mm, 6mm, 9mm, 11mm, and 15mm) showed values over 50 kPa for all cases, which represents more than 100% increase over background (~21kPa). We considered a 2cm diameter circular region of interest for all phantom experiments. Mean elasticity (Emean) values varied from 26 kPa to 73 kPa, depending on the macrocalcification size. Highly dense clusters of microcalcifications showed higher Emax values than clusters of microcalcification with low concentrations, but the difference in Emean values was not significant. CONCLUSIONS: Our results demonstrate that the presence of large isolated macrocalcifications and highly concentrated clusters of microcalcifications can introduce areas with apparent high elasticity in SWE. Considering that benign breast masses normally have significantly lower elasticity values than malignant tumors, such areas with high elasticity appearing due to presence of calcification in benign breast masses may lead to misdiagnosis. PMID- 26368941 TI - Refractory bipolar disorder and neuroprogression. AB - Immune activation and failure of physiologic compensatory mechanisms over time have been implicated in the pathophysiology of illness progression in bipolar disorder. Recent evidence suggests that such changes are important contributors to neuroprogression and may mediate the cross-sensitization of episode recurrence, trauma exposure and substance use. The present review aims to discuss the potential factors related to bipolar disorder refractoriness and neuroprogression. In addition, we will discuss the possible impacts of early therapeutic interventions as well as the alternative approaches in late stages of the disorder. PMID- 26368942 TI - Using Co-Expression Analysis and Stress-Based Screens to Uncover Arabidopsis Peroxisomal Proteins Involved in Drought Response. AB - Peroxisomes are essential organelles that house a wide array of metabolic reactions important for plant growth and development. However, our knowledge regarding the role of peroxisomal proteins in various biological processes, including plant stress response, is still incomplete. Recent proteomic studies of plant peroxisomes significantly increased the number of known peroxisomal proteins and greatly facilitated the study of peroxisomes at the systems level. The objectives of this study were to determine whether genes that encode peroxisomal proteins with related functions are co-expressed in Arabidopsis and identify peroxisomal proteins involved in stress response using in silico analysis and mutant screens. Using microarray data from online databases, we performed hierarchical clustering analysis to generate a comprehensive view of transcript level changes for Arabidopsis peroxisomal genes during development and under abiotic and biotic stress conditions. Many genes involved in the same metabolic pathways exhibited co-expression, some genes known to be involved in stress response are regulated by the corresponding stress conditions, and function of some peroxisomal proteins could be predicted based on their co expression pattern. Since drought caused expression changes to the highest number of genes that encode peroxisomal proteins, we subjected a subset of Arabidopsis peroxisomal mutants to a drought stress assay. Mutants of the LON2 protease and the photorespiratory enzyme hydroxypyruvate reductase 1 (HPR1) showed enhanced susceptibility to drought, suggesting the involvement of peroxisomal quality control and photorespiration in drought resistance. Our study provided a global view of how genes that encode peroxisomal proteins respond to developmental and environmental cues and began to reveal additional peroxisomal proteins involved in stress response, thus opening up new avenues to investigate the role of peroxisomes in plant adaptation to environmental stresses. PMID- 26368943 TI - Basal forebrain neuronal inhibition enables rapid behavioral stopping. AB - Cognitive inhibitory control, the ability to rapidly suppress responses inappropriate for the context, is essential for flexible and adaptive behavior. Although most studies on inhibitory control have focused on the fronto-basal ganglia circuit, we found that rapid behavioral stopping is enabled by neuronal inhibition in the basal forebrain (BF). In rats performing the stop signal task, putative noncholinergic BF neurons with phasic bursting responses to the go signal were nearly completely inhibited by the stop signal. The onset of BF neuronal inhibition was tightly coupled with and temporally preceded the latency to stop, the stop signal reaction time. Artificial inhibition of BF activity in the absence of the stop signal was sufficient to reproduce rapid behavioral stopping. These results reveal a previously unknown subcortical mechanism of rapid inhibitory control by the BF, which provides bidirectional control over the speed of response generation and inhibition. PMID- 26368945 TI - Mentoring and Self-Efficacy: Implications for the Neonatal Nurse Practitioner Workforce. AB - BACKGROUND: Mentoring facilitates positive self-efficacy. Individuals with high self-efficacy emulate professional resiliency and possess a strong sense of optimism in their ability to adapt, overcome, and persevere in the professional arena. PURPOSE: The purpose of this study was to identify characteristics that encourage mentoring relationships between neonatal nurse practitioner (NNP) students and preceptors, as well as student perceptions of mentoring relationships. METHODS: A 29-item survey composed of demographic items, the Freeman Mentoring Survey, the Self-Efficacy Scale, and the Confidence Scale, along with qualitative questions, was disseminated to NNP students enrolled in their final clinical practicum course from August to October 2014. RESULTS: Students who sought out their own preceptor "by choice" reported higher self efficacy scores (P = .046) and mentoring scores (P = .047). Students who perceived their preceptor as a mentor (91%) expressed readiness to assume the role of advanced practice registered nursing after graduation. An average of 37.2 hours is required for a student to adapt to a clinical site and preceptor. IMPLICATIONS FOR PRACTICE: Mentorships between preceptors and NNP students, grounded in the provisions of trust, stability, encouragement, and hope, facilitate positive self-efficacy for the student learner. All NNPs must commit to the integration of mentoring programs in the clinical setting as well as seek out teaching-coaching opportunities with NNP students to demonstrate their unwavering commitment to the NNP workforce. IMPLICATIONS FOR RESEARCH: Further investigation of the impacts of mentoring relationships upon job satisfaction, recruitment and retention, the teaching-coaching role, and scholarship activities of actively practicing NNPs is indicated. PMID- 26368944 TI - ScaleS: an optical clearing palette for biological imaging. AB - Optical clearing methods facilitate deep biological imaging by mitigating light scattering in situ. Multi-scale high-resolution imaging requires preservation of tissue integrity for accurate signal reconstruction. However, existing clearing reagents contain chemical components that could compromise tissue structure, preventing reproducible anatomical and fluorescence signal stability. We developed ScaleS, a sorbitol-based optical clearing method that provides stable tissue preservation for immunochemical labeling and three-dimensional (3D) signal rendering. ScaleS permitted optical reconstructions of aged and diseased brain in Alzheimer's disease models, including mapping of 3D networks of amyloid plaques, neurons and microglia, and multi-scale tracking of single plaques by successive fluorescence and electron microscopy. Human clinical samples from Alzheimer's disease patients analyzed via reversible optical re-sectioning illuminated plaque pathogenesis in the z axis. Comparative benchmarking of contemporary clearing agents showed superior signal and structure preservation by ScaleS. These findings suggest that ScaleS is a simple and reproducible method for accurate visualization of biological tissue. PMID- 26368946 TI - Characteristics of methods of suicide attempts in Korea: Korea National Suicide Survey (KNSS). AB - BACKGROUND: Because the method used for a suicide attempt is an important determinant of outcome, these methods should be explored. The present study was a nationwide investigation of suicide attempts and the characteristics of suicidal behavior. AIMS: To compare the suicide methods used in attempted suicides with those used in completed suicides and to examine the factors associated with each phenomenon. METHODS: The present study reviewed the medical charts of subjects who had attempted suicide and subsequently visited the emergency rooms of 17 medical centers from May 1, 2013 to November 7, 2013. All subjects completed a full psychiatric interview conducted by trained psychiatric residents. Suicide attempt methods were divided into the following six categories: drug poisoning, pesticide poisoning, gassing, cutting, hanging, and others. The associations among demographic variables, related psychiatric variables, and suicide-attempt methods were analyzed using a multinomial regression analysis. RESULTS: Of the 1359 suicide attempts or instrumental suicide-related behaviors with/without injuries and the 14,160 completed suicides, drug poisoning and cutting were the most common suicidal behaviors with/without injuries, but they were the least frequent method of completed suicides. In contrast, hanging and jumping from a height were less common among failed suicide attempts but resulted in a higher percentage of fatalities. Being male, age, and area of residence were associated with pesticide poisoning, whereas previous suicide attempts were associated with cutting, pesticide poisoning, and gassing. CONCLUSION: A previous suicide attempt is a risk factor for suicide; thus, assessing the characteristics of suicide attempts or instrumental suicide-related behaviors with/without injuries is necessary to prevent these attempts. The present findings showed that the methods of suicide used by individuals who only attempted suicide differed from those used by individuals who completed. Of the suicide methods, pesticide poisoning was related to age, residential area (urban), and a history of previous suicide attempts. PMID- 26368947 TI - Late onset mania as an organic syndrome: A review of case reports in the literature. AB - AIMS: Although First Episode Mania presenting over the age of 50 is reported in several cases, there has been little systematic compilation of these case reports. We report a review of case reports on these subjects. METHODS: We undertook a literature search on MEDLINE, PsychInfo and EMBASE to identify case reports of first episode of mania or hypomania presenting over the age of 50. RESULTS: 35 cases were identified. 29/35 (82%) had a suspected underlying organic cause. Organic causes included vascular causes, iatrogenic drug use, electrolyte imbalance, dementia and thyroid disease. Vascular risk factors were present in 17/35 cases (48%). In 10/35 (28%) of cases organic treatment contributed to successful remission of the manic episode. LIMITATIONS: As evidently not all cases have been reported the main limitation is that of publication bias for this paper. Any such hypothesis generated from studying these cases would require replication in prospective longitudinal trials of this cohort of patients. CONCLUSIONS: This review of case reports appears to add to evidence of late onset mania having an organic basis. Whether this is a separate organic syndrome remains to be established. Our provisional findings suggest that such patients should have a thorough medical and psychiatric screening in identifying an underlying cause. PMID- 26368948 TI - The World Health Organization (WHO) dataset for guiding suicide prevention policies: A 3-decade French national survey. AB - BACKGROUND: Public health policies aim to prevent suicide in the general population. Assessing their effectiveness is required to further guide public health policies. The present article focuses on the French paradox. The French health care system was classified as the best in the world according the World Health Organization (WHO). However, suicide rates in France remain high compared to other European countries. The aim of the present article was to analyze (i) the evolution of suicide Age-Standardized Death (ASDRs) in France during the last three decades and the associations with socio-economic parameters and (ii) to understand which populations may specifically benefit from further targeted suicide prevention policies. METHODS: The database of the World Health Organization (WHO), freely available, was explored in April 2015. ASDRs were calculated each year by ratio between the number of deaths by suicide and the total population (per 100,000 inhabitants). Number of deaths by gender and age were also analyzed. RESULTS: Overall, ASDR suicide has decreased since 1987 in France (-32.8% between 1987 and 2010). However, France kept the same rank (10/26) when compared to other European countries between 1987 and 2010. The relative burden of suicide in all-causes mortality increased during the same period (+28.2%) while the total number of deaths by suicide increased only slightly (+3.9%). More specifically, the number of deaths by suicide increased substantially in [35-54] years old (+40%) and 75+ years old (+27%) males, and in [35-54] (+41%) years old females. Between 2000 and 2010, suicide rates significantly decreased when yearly mean income increased, and when general and psychiatric care beds decreased. CONCLUSION: Although ASDR suicide has decreased in France since 1987, this decline is quite modest when considering its universal access to care, the prevention of depression and suicide public policies. Suicide prevention public policies should focus on evaluation and improvement of prevention and care in the [35-54] years old population, and in the males aged 75+. PMID- 26368950 TI - Sinusoidal phase-modulating self-mixing interferometer with nanometer resolution and improved measurement velocity range. AB - A new signal-processing method based on an electronic frequency down-conversion technique has been introduced into a sinusoidal phase-modulating, self-mixing interferometer. The developed interferometer employs an electro-optical crystal placed in the external cavity of a He-Ne laser to generate the sinusoidal phase modulation with high modulation rate and ultralow insertion loss. Phase quadrature signals which have been amplitude-modulated by the sine and cosine functions, respectively, of the measured displacement can be extracted from the high-density optical fringes through the use of dual-channel multiplier/filter circuits. Therefore, the displacement of the external target can be retrieved from the phase quadrature signals with nanometer resolution and high computational efficiency. Moreover, a much-improved measurement speed from 2.5 to 22 mm/s has been realized owing to the simplified signal-processing method. The performance of the proposed interferometer has been experimentally verified by comparison to an Agilent 5529A dual-frequency laser interferometer. The measurement results from the two instruments agree well, and we therefore expect that our new technique offers a powerful instrument for high-speed metrology sciences. PMID- 26368949 TI - Longitudinal impact of a collaborative care model on employment outcomes in bipolar disorder. AB - BACKGROUND: Few treatments are available to directly address employment or work functioning among individuals with bipolar disorder (BD) and currently available treatment models have not been evaluated to examine their impact employment outcomes. We examined impact of affective symptoms and health-related quality of life (HRQoL) on longitudinal employment outcomes in a community-based sample of individuals with bipolar disorder who completed the Life Goals-Collaborative Care (LG-CC) intervention. METHODS: Participants (N=178) were assessed based on HRQoL, employment status, affective symptoms (depressive/manic), and work hours at baseline, 6-, 12- and 24-months after initiation of LG-CC. Frequency of LG-CC sessions and number of care-manager contacts also were ascertained. RESULTS: At baseline, 21% were employed, 29.5% were unemployed, and 49.6% were on disability. Improvement in affective symptoms was seen over the 24-month period, but not in HRQoL. Lower depression symptoms, but not mania, at baseline predicted greater likelihood of employment status in 24-months. Degree of LG-CC participation was associated with a reduced likelihood of becoming disabled/unemployed and increased number of hours worked in 24-months. LIMITATIONS: The study was originally designed to compare implementation strategies and not the effectiveness of LG-CC on employment outcomes. Further, it was unclear whether improvement in work functioning were personal goals of the participants of this study. CONCLUSIONS: Fewer depressive symptoms were associated with positive employment outcomes over time. Collaborative Care Models that are already implemented by existing providers that focus on management of affective symptoms show promise in positively impacting employment outcomes. PMID- 26368951 TI - Enhanced environmental performance of fiber optic gyroscope by an adhesive potting technology. AB - An adhesive potting technology for fiber coils of a fiber optic gyroscope (FOG) is proposed. The fiber coil is immersed in liquid adhesive with superior mechanical properties. The internal air is first removed completely by vacuum pumping, and the adhesive is then evenly pressed into the fiber coil under pressure. The potted fiber core is prepared by ladder-type temperature curing and a stress-release process. With this potting technology, the vibration performance of an FOG is greatly improved and, at the same time, will not lead to degradation of its temperature performance. Using this potting technique of adhesive impregnation, the adaptability of FOGs will be enhanced. PMID- 26368952 TI - Direct polishing of aluminum mirrors with higher quality and accuracy. AB - Diamond-turned aluminum mirrors have been widely used in modern optical systems. However, the machined surfaces have characteristic periodic tool marks, which contribute to reduced optical performance by creating effects such as scattering and distortion. This paper develops a new polishing technology to polish aluminum mirrors directly to remove tool marks and improve surface quality and surface accuracy. A Taguchi experiment was used to obtain optimal polishing conditions for reducing surface roughness, and computer-controlled optical surfacing technology was employed for form correction of aluminum mirrors. PMID- 26368953 TI - Single-lens 3D digital image correlation system based on a bilateral telecentric lens and a bi-prism: validation and application. AB - By using the principle of stereovision, 3D digital image correlation (3D-DIC) can determine the 3D morphology and deformation of a target and has been widely used in experimental mechanics as a noncontact 3D measurement technique. To eliminate the limitations of the conventional 3D-DIC system, this study proposes a calibration-free single-lens 3D-DIC system based on a bilateral telecentric lens and a bi-prism. The performance of the proposed system is verified by tests of rigid-body translation along the out-of-plane direction. As a comparison, the same rigid-body translations are measured using a single-entocentric-lens 3D-DIC system. The results show that the measurement accuracy of the proposed system is higher than that of the entocentric-lens-based one. As an application, the proposed system is used to measure the thermal linear expansion of a ceramic plate at elevated temperatures. The reasonable measurement results verify its applicability in deformation measurements, even in high-temperature environments. PMID- 26368954 TI - Large area x-ray collimator-the zone plate approach. AB - One question of particular interest in the measurement of x-ray imaging optics for space telescopes concerns the characteristics of the point spread function (PSF) in orbit and the focal length for an infinite source distance. In order to measure such a PSF, a parallel x-ray beam with a diameter of several centimeters to meters is required. For this purpose a large area transmission x-ray zone plate (ZP) for collimating x-ray beams has been designed, built, and tested. Furthermore we present a setup to determine large-scale aberrations of the collimated beam. From x-ray measurements we obtain an upper limit for the angular resolution of +/-0.2 arc sec and a first-order diffraction efficiency of ~13%. These results show that it is possible to use a ZP as a collimator for the PANTER x-ray test facility. PMID- 26368955 TI - 3D localization of high particle density images using sparse recovery. AB - If particles are too close in space, their images may be overlapped when they are observed with microscopes because of diffraction limitation, which makes them difficult to be distinguished or localized. This limitation also affects the efficiency of localization of those single-particle-localization microcopies, such as stochastic optical reconstruction microscopy (STORM) and (fluorescence) photoactivated localization microscopy [(F)PALM]. In this work, we developed a 3D sparse recovery (3D-SR) method, with the aim of localizing particles with high density in three dimensions, which cannot be resolved using original STROM or (F)PALM. A cylindrical lens was introduced to a traditional wide-field microscope in order to form the 3D point spread function for 3D-SR. The performance of the 3D-SR method was evaluated using simulation. Simulated results demonstrated that, even for particle densities as high as 4 MUm-2 on a transversal projection, particles could still be localized with high accuracy. The standard deviations were found to be 25.59 nm along the transverse direction and 50.42 nm along the axial direction. Compared with the existing 3D localization methods used in high particle density cases, such as 3D-DAOSTORM, 3D-SR allows a higher activated fluorophore density per frame. PMID- 26368956 TI - Diode-pumped 2-MUm pulse laser with noncomposite Tm,Ho:YLF rod conduction-cooled down to -80 degrees C. AB - Q-switched operation of a diode-side-pumped, conduction-cooled Tm,Ho:YLF laser oscillator with 100-mJ output at a pulse repetition rate of 20 Hz and an eye-safe wavelength of 2-MUm was achieved. The noncomposite Tm,Ho:YLF laser rod was conduction-cooled down to -80 degrees C through thermal contact of In films from Cu heat sinks, and the laser diode arrays were conduction-cooled to approximately 20 degrees C using Cu heat sinks in a vacuum container. A ring resonator of 3.86 m length with an acousto-optic Q-switch was used. The pulse width was 125 ns, and optical-to-optical efficiency was approximately 7% for an output of 100 mJ. The laser is used at 2.05 MUm for applications of Doppler wind lidar measurements, CO2 differential absorption lidar measurements, and aerosol profiling. PMID- 26368957 TI - Real-time point-diffraction interferometer and its analytical formulation. AB - We propose a novel wavefront sensor and study its performance with an analytical formulation. The sensor has a polarizing point-diffraction beam splitter. Using transmitted and reflected beams, we can build a real-time point-diffraction interferometer with high precision and efficiency. Our analytical studies reveal that wavefront errors might be measured incorrectly and that less precise estimates of wavefronts appear as the pinhole radius Rpin is increased. An investigation of propagating uncertainties shows that the wavefront measurement can be calibrated by estimating the pinhole effects and the polarizing properties with a precision of a few percent. Based on these studies, Rpin should be smaller than half of the Airy disk for better performance. PMID- 26368958 TI - Bending characteristics of a long-period fiber grating in a hollow eccentric optical fiber. AB - In this paper, the bending characteristics of a long-period fiber grating (LPFG) in a hollow eccentric optical fiber (HEOF) have been investigated. Two samples fabricated under different laser exposure directions have been studied experimentally. The results show that the HEOF-LPFG can distinguish specific bending directions. The resonant peak shifts linearly with increasing curvature, but its sensitivity is lower than that of the LPFGs in single-mode fibers. In addition, the exposure direction shows a great influence on the bending characteristics due to the asymmetry of the fiber core. Furthermore, the responses of the HEOF-LPFG to temperature, axial strain, and external refractive index have been measured. PMID- 26368959 TI - Output characterization of a fiber optic parametric oscillator based on multiple four-wave mixing. AB - The output characteristics of a fiber optic parametric oscillator (FOPO) based on multiple four-wave mixing (multi-FWM) processes are investigated numerically and demonstrated experimentally. The theoretical model of a FOPO based on multi-FWM processes is presented. It is proved that the output signal starts to saturate when the high-order parametric products are generated in the multi-FWM processes of FOPOs. Moreover, a higher output power of the idler (i.e., the first-order parametric product) is achieved. On the other hand, the pump power is proved to be a key factor that significantly influences the output of the FOPO. PMID- 26368960 TI - SI traceable algorithm for characterizing hyperspectral infrared sounder CrIS noise. AB - The Cross-track Infrared Sounder (CrIS) on the Suomi National Polar-orbiting Partnership Satellite (S-NPP) is a Fourier transform spectrometer and provides the sensor data record (SDR) that can be used to retrieve atmospheric temperature and water vapor profiles and can also be directly assimilated in numerical weather prediction models. The noise equivalent differential radiance (NEdN) is part of CrIS SDR products and represents the amount of random noise in the interferometer data. It is a crucial parameter that affects the accuracy of retrieval and satellite radiance assimilation. In this study, we used the international system of units (SI) traceable method Allan deviation to estimate the CrIS NEdN because the internal calibration target (ICT) radiance was slowly varying with time. Compared to the current standard deviation method, this study shows that the NEdN calculated from Allan deviation is converged to a stable value when a number of samples or the average window size is set to 510. Thus, Allan deviation can result in CrIS NEdN SI traceable noise. An optimal averaging window size is 30 if the NEdN is calculated from the standard deviation. PMID- 26368961 TI - Measurement of complex amplitude with a point-diffraction interferometer. AB - We propose a pupil-plane wavefront sensor to measure instantaneous phase and amplitude aberrations, developing the configuration of the point-diffraction interferometer proposed by Imada et al. [Appl. Opt. (2015), accepted]. The previous configuration allows us to instantaneously acquire four phase-shifted interferograms, from which cosine and sine functions of the relative phase difference between the test and reference beams can be derived. Here, because the wavefront phase can be reconstructed from only its sine function when the aberration of the input beam is smaller than half that of the sensing wavelength, we directly measure the intensities of the test and the reference beams instead of two of the four interferograms. Using this proposed configuration enables reconstruction of not only the wavefront phase but also its amplitude. The conceptual design of the proposed sensor is described, and its performance is evaluated compared with the original point-diffraction interferometer through numerical simulations. PMID- 26368962 TI - Responsivity optimization in magneto-optic sensors based on ferromagnetic materials. AB - In an effort to optimize magnetic field detection sensitivities, the Faraday responsivity vector, which determines the relationship between the Faraday rotation angle and an externally applied magnetic field, was investigated in magneto-optic sensors based on bismuth-doped iron-garnet films. Under externally applied fields, Faraday rotation is produced principally by domain rotation and domain wall motion, whose relative contributions depend on the domain geometry and the direction of laser propagation. When optically probed along a principal magnetization axis, Faraday rotation is driven by a single magnetization mechanism, and the responsivity is linearized (reduced to an effective Verdet constant). When the films are probed along an oblique angle to the principal axes, the relationship between the Faraday rotation and the external field becomes tensorial and much more complex. Although this may lead to more complicated phenomena, the interplay of domain rotation and domain wall bowing can be exploited to improve responsivity or bandwidth. A generalized model for the magnitude and direction of the responsivity vector is formulated, which gives predictions that are consistent with the experimental data. Applications to arrayed sensors and three-axis field measurements are discussed. PMID- 26368963 TI - Unidirectional dissipative soliton operation in an all-normal-dispersion Yb-doped fiber laser without an isolator. AB - We demonstrate self-started unidirectional dissipative soliton operation and noise-like pulse operation in an all-normal-dispersion bidirectional Yb-doped fiber laser mode-locked by nonlinear polarization rotation. The laser works unidirectionally once mode-locking is achieved due to the cavity directional nonlinearity asymmetry along with the nonlinear polarization rotation mode locking mechanism. PMID- 26368964 TI - Co-phasing of the segmented mirror and image retrieval based on phase diversity using a modified algorithm. AB - The conventional Broyden-Fletcher-Goldfarb-Shanno (BFGS) method used to solve the cost function of a phase diversity (PD) algorithm converges to a global optimum only when the cost function is convex. We present a modified BFGS method, which has fine global convergences for both convex and nonconvex functions, guarantees that the solutions will converge to the global minimum, corresponding to the actual wavefront coefficients, and apply it to minimize the PD cost function to co-phase the segmented active optics system and recover the unknown object under different noise levels. The noise amplification effect on the accuracy of the algorithm is removed by our proposed estimated strategy of the regularization parameter for the PD problem. The vast contrast results demonstrate that the modified method has a much higher accuracy than the conventional BFGS method for the nonconvex condition even under a considerably high noise level. PMID- 26368965 TI - Measurement of accommodation response of human eye to integral floating display. AB - The dioptric responses of human eyes to floating images at different depths reconstructed by an integral floating display are measured with an open-field autorefractor and analyzed according to observer recognition of the accommodation depth cue. Two targets are randomly presented approximately 1.75 D from the observers and have a separation of 0.15 D, corresponding to approximately 5 cm. Two subjects participate, and over 500 responses are measured during each experimental trial. The frequency distribution profiles of the responses to targets at different locations are obtained and analyzed. The results confirm that the subjects focused on the floating targets and not on the surface of the optical component. In this paper, an analysis of the separation between the peaks of the frequency distribution profiles is presented that confirms that the integral floating display could induce the accommodation response to provide the corresponding depth stimulus. PMID- 26368966 TI - Enhancing light absorption within the carrier transport length in quantum junction solar cells. AB - Colloidal quantum dot (CQD) solar cells have attracted tremendous attention because of their tunable absorption spectrum window and potentially low processing cost. Recently reported quantum junction solar cells represent a promising approach to building a rectifying photovoltaic device that employs CQD layers on each side of the p-n junction. However, the ultimate efficiency of CQD solar cells is still highly limited by their high trap state density in both p- and n-type CQDs. By modeling photonic structures to enhance the light absorption within the carrier transport length and by ensuring that the carrier generation and collection efficiencies were both augmented, our work shows that overall device current density could be improved. We utilized a two-dimensional numerical model to calculate the characteristics of patterned CQD solar cells based on a simple grating structure. Our calculation predicts a short circuit current density as high as 31 mA/cm2, a value nearly 1.5 times larger than that of the conventional flat design, showing the great potential value of patterned quantum junction solar cells. PMID- 26368967 TI - Experimental method of determination of parameters of cemented doublet. AB - This work analyzes a method to determine the internal parameters of an optical system of a classical cemented doublet or a three-element tunable-focus lens (a tunable-focus doublet), which is an equivalent of the classical cemented doublet. The method is noninvasive, and the parameters are calculated without any damage or dismantling of the lens. PMID- 26368968 TI - All-optical logic gates based on nonlinear plasmonic ring resonators. AB - A nonlinear plasmonic T-shaped switch based on a square-shaped ring resonator is simulated by the finite-difference time-domain numerical method. Three optical logic gates-a NOT, with one T-shaped switch, and AND and NOR gates, each with two cascaded T-shaped switches-are proposed. The nonlinear Kerr effect is utilized to show the performance of our proposed logic gates. The values of transmission at the ON and OFF states of NOT and NOR gates are 70% and less than 0.6% of the input lightwave, respectively, while these values for the AND gate are 90% and less than 30%, respectively. PMID- 26368969 TI - Magneto-optical properties of one-dimensional conjugated photonic crystal heterojunctions containing plasma layers. AB - In this paper, a 4*4 transfer matrix method has been used to investigate the optical and magneto-optical properties of 1D conjugated photonic crystal (CPC) heterojunctions containing plasma layers. A linearly polarized TM wave is obliquely incident onto stack. A large Faraday rotation as well as high transmission can be achieved simultaneously in our proposed structure. The influences of the external magnetic field, number of unit cells, incidence angle, and plasma frequency on the transmission and Faraday rotation angle have been analyzed. Results indicate that the proposed structure has strong enhancement of Faraday rotation angle with relatively high transmission. This prospective advantage of the structure is useful for tunable filters in the millimeter-wave region. PMID- 26368970 TI - Modeling plasmonic efficiency enhancement in organic photovoltaics. AB - Efficiency enhancement of bulk heterojunction (BHJ) organic solar cells by means of the plasmonic effect is investigated by using finite-difference time-domain (FDTD) optical simulations combined with analytical modeling of exciton dissociation and charge transport efficiencies. The proposed method provides an improved analysis of the cell performance compared to previous FDTD studies. The results of the simulations predict an 11.8% increase in the cell's short circuit current with the use of Ag nano-hexagons. PMID- 26368971 TI - Highly efficient solid-state distributed feedback dye laser based on polymer filled nanoporous glass composite excited by a diode-pumped solid-state Nd:LSB microlaser. AB - Realization of a compact, robust, highly stable, and efficient solid-state distributed feedback (DFB) dye laser based on pyrromethene 580-doped modified poly-(methyl methacrylate) embedded into nanoporous glass host is reported. A diode-pumped solid-state STA01SH-500 Nd:LSB microlaser (lambda=532 nm; tau0.5~0.5 ns; EP<=80 MUJ; f<=500 Hz) is used as a pump source. When pumped well above threshold, a DFB laser emits a train of ultrashort pulses (tau<=1 ns; tau0.5<0.5 ns; Deltalambda0.5<=0.01 nm), while at excitation intensities not far from threshold, single transform limited picosecond pulses (tau0.5<=40 ps; tau0.5Deltanu0.5~0.3), tunable from 541 to 598 nm, are generated. The DFB lasing efficiency reaches ~60% upon an energy stability of ~1.4% and an overall service life of the active element of ~9*107 laser shots. More than an order of magnitude increase in the temperature stability of a lasing wavelength as compared with ethanol solutions of laser dyes is practically demonstrated. PMID- 26368972 TI - Reliable chromatic dispersion measurement method for installed optical fibers. AB - We propose and experimentally demonstrate a reliable chromatic dispersion measurement method for installed optical fibers. This technique is based on a modified Sagnac interferometer which is polarization-independent, hence no polarization controller device is needed to control the polarization state of the light entering into the interferometer during measurement. In our proposed system, the polarization mode dispersion (PMD) of the test fiber is compensated by employing a Faraday rotator mirror at one end of the fiber, so that the measured dispersion results will not be affected by any external perturbations on the test fiber. In addition, our method is single-ended, rapid (<1 s), and accurate. Experimental results show the differences for dispersion and dispersion slope of only 0.17% and 1.24%, respectively, compared with that of a commercial instrument. All characteristics indicate that our approach is indeed suitable for in-field dispersion measurement of installed fibers. PMID- 26368973 TI - Temperature measurement of mineral melt by means of a high-speed camera. AB - This paper presents a temperature evaluation method by means of high-speed, visible light digital camera visualization and its application to the mineral wool production process. The proposed method adequately resolves the temperature related requirements in mineral wool production and significantly improves the spatial and temporal resolution of measured temperature fields. Additionally, it is very cost effective in comparison with other non-contact temperature field measurement methods, such as infrared thermometry. Using the proposed method for temperatures between 800 degrees C and 1500 degrees C, the available temperature measurement range is approximately 300 K with a single temperature calibration point and without the need for camera setting adjustments. In the case of a stationary blackbody, the proposed method is able to produce deviations of less than 5 K from the reference (thermocouple-measured) temperature in a measurement range within 100 K from the calibration temperature. The method was also tested by visualization of rotating melt film in the rock wool production process. The resulting temperature fields are characterized by a very good temporal and spatial resolution (18,700 frames per second at 128 pixels*328 pixels and 8000 frames per second at 416 pixels*298 pixels). PMID- 26368974 TI - Grating configurations to compress extreme-ultraviolet ultrashort pulses. AB - It is here discussed the design of ultrafast extreme-ultraviolet (XUV) grating compressors that can be used to condition the spectral phase of ultrashort chirped pulses to compensate for the phase chirp and get closer to the Fourier limit. We discuss the two configurations that can be used to realize the compressor, the classical diffraction mount, and the off-plane one. The concept is applied to the realization of a XUV compressor with applications to free electron lasers. PMID- 26368975 TI - Application of Fresnel diffraction from phase steps to measurement of etching rate of transparent materials. AB - Based on Fresnel diffraction from phase steps, we present an optical method for real-time monitoring and measurement of thickness during the wet etching of transparent materials. It is shown experimentally that during the etching process, the visibility of diffraction fringes varies periodically with time (thickness) and the rate the etching is measured. Using dilute etching solutions, we measured an average etching rate of 5.3 nm/s for glass. PMID- 26368976 TI - Phase shifting interferometry using a spatial light modulator to measure optical thin films. AB - This work describes a process for measuring thin film steps, using phase shifting interferometry (PSI). The phase shifts are applied only in the region where the thin film steps are located. The phase shift is achieved by displaying different gray levels on a spatial light modulator (SLM Holoeye LC2012) placed in one arm of a Twyman-Green (T-G) interferometer. Before measuring the thin film steps, it was necessary to quantify the phase shifts achieved with this SLM by measuring the fringe shifts in experimental interferograms. The phase shifts observed in the interference patterns were produced by displaying the different gray levels on the SLM one by one, from 0 to 255. The experimental interferograms and the thicknesses of the thin film steps were successfully quantified, proving that this method can be used to measure thin films by applying the PSI method only on the region occupied by them. PMID- 26368977 TI - Investigating the optical properties of polycrystalline AgCl(1-x)Br(x) (0<=x<=1) and Ag(0.95)Tl(0.05)Br(0.95)I(0.05) for IR engineering. AB - Using the Michelson technique we measured the refractive indices for the plane parallel thin plates made of AgCl1-xBrx(0<=x<=1) and, to the best of our knowledge, for the first time for the Ag0.95Tl0.05Br0.95I0.05 plate, manufactured by hot embossing, at 632.8 nm. We recorded their absorption spectra within the range of 0.19-41.67 MUm using UV-Vis spectrophotometry and Fourier transform infrared spectroscopy, which demonstrated that the increase of substituent silver bromide or thallium monoiodide mole fraction in the corresponding solid solution causes the optical density to grow. As the result it moves the transmission edges toward longer wavelengths, while slightly reducing the transmission peak. PMID- 26368978 TI - Study on magnetic mirror array image intensifier to work at room temperature. AB - In order to improve the detection capability of the current low-light-level (LLL) imaging systems at room temperature, a new device, a magnetic mirror array image intensifier (MMAII), is proposed in this paper. A magnetic mirror array device (MMAD) is coupled into an image intensifier which sits between the photocathode and the microchannel plate (MCP). The trace photoelectrons, one after another, are first sufficiently accumulated by the MMAD over a long time at room temperature, and then they are released and enter the MCP for further gain. These two steps are used to improve the detection capability at the LLL imaging system at room temperature. After the two-dimensional magnetic field distribution of the magnetic mirror array (MMA) is calculated, the MMA is designed and optimized with a rubidium Nd-Fe-B permanent magnet. Three groups of ideal parameters for the Nd Fe-B permanent magnet MMAD, with a magnetic mirror ratio of 1.69, for all of them have been obtained. According to the research results on the noise of the escape cone of the MMAII, the angle between the incident direction and the axis is greater than 57 degrees , so the trace electrons must be constrained by the magnetic mirror. We made 54 MMAs from Nd-Fe-B permanent magnets and packaged them in a container. Then the system was evacuated to 10-3 Pa at room temperature. It was found by experiment that the trace electrons could be actually constrained by the MMAD. The MMAII can be applied to images for static LLL objects. PMID- 26368979 TI - Nanosprings harvest light more efficiently. AB - Nanotechnology presents versatile architectural designs for the purpose of utilization as a building block of 1D optoelectronic nanodevices because current nanowire-based schemes require more effective solutions for low absorption capacity of nanoscale volumes. We report on the potential of nanospring absorbers as an alternative light-harvesting platform with significant advantages over conventional nanowires. Absorption capacity of nanospring geometry is found to be superior to cylindrical nanowire shape. Unlike nanowires, they are able to trap a larger amount of light thanks to characteristic periodic behavior that boosts light collection for the points matched with Mie resonances. Moreover, nanospring shape supplies compactness to a resulting device with area preservation as high as twofold. By considering that a nanospring array with optimal periods yields higher absorption than individual arrangements and core-shell designs, which further promote light collection due to unique antireflection features of shell layer, these nanostructures will pave the way for the development of highly efficient self-powered nanosystems. PMID- 26368981 TI - Resident Rounds: Part III - Case Report: Argyria - A Case of Blue-Gray Skin. AB - Argyria is an uncommon blue-gray pigmentation of the skin (increased in sun exposed areas), nail unit, and mucous membranes caused by prolonged silver exposure. Commonly occurs in the setting of occupational exposure, silver containing medications, or systemic absorption from use of silver sulfadiazine on extensive burns/wounds. Recently, there appears to be an increase in the practice of colloidal silver ingestion given the popularity and easy availability of alternative medicines and dietary supplements containing various silver containing compounds. We report a case of argyria in a 72-year-old male following ingestion of colloidal silver as a supplement for over 10 years. He had a diffuse, blue-gray discoloration of his face and nails. A skin biopsy was performed and histology supported the clinical diagnosis of argyria. Our objective is to increase the awareness for this rare dermatologic entity by highlighting the clinical and histological features through a case report. Dermatologists should warn patients in regards to the use of colloidal silver for alternative health practices. PMID- 26368980 TI - Midregional-proAtrial Natriuretic Peptide and High Sensitive Troponin T Strongly Predict Adverse Outcome in Patients Undergoing Percutaneous Repair of Mitral Valve Regurgitation. AB - BACKGROUND: It is not known whether biomarkers of hemodynamic stress, myocardial necrosis, and renal function might predict adverse outcome in patients undergoing percutaneous repair of severe mitral valve insufficiency. Thus, we aimed to assess the predictive value of various established and emerging biomarkers for major adverse cardiovascular events (MACE) in these patients. METHODS: Thirty four patients with symptomatic severe mitral valve insufficiency with a mean STS Score for mortality of 12.6% and a mean logistic EuroSCORE of 19.7% undergoing MitraClip therapy were prospectively included in this study. Plasma concentrations of mid regional-proatrial natriuretic peptide (MR-proANP), Cystatin C, high-sensitive C-reactive protein (hsCRP), high-sensitive troponin T (hsTnT), N-terminal B-type natriuretic peptide (NT-proBNP), galectin-3, and soluble ST-2 (interleukin 1 receptor-like 1) were measured directly before procedure. MACE was defined as cardiovascular death and hospitalization for heart failure (HF). RESULTS: During a median follow-up of 211 days (interquartile range 133 to 333 days), 9 patients (26.5%) experienced MACE (death: 7 patients, rehospitalization for HF: 2 patients). Thirty day MACE-rate was 5.9% (death: 2 patients, no rehospitalization for HF). Baseline concentrations of hsTnT (Median 92.6 vs 25.2 ng/L), NT-proBNP (Median 11251 vs 1974 pg/mL) and MR-proANP (Median 755.6 vs 318.3 pmol/L, all p<0.001) were clearly higher in those experiencing an event vs event-free patients, while other clinical variables including STS-Score and logistic EuroSCORE did not differ significantly. In Kaplan-Meier analyses, NT proBNP and in particular hsTnT and MR-proANP above the median discriminated between those experiencing an event vs event-free patients. This was further corroborated by C-statistics where areas under the ROC curve for prediction of MACE using the respective median values were 0.960 for MR-proANP, 0.907 for NT proBNP, and 0.822 for hsTnT. CONCLUSIONS: MR-proANP and hsTnT strongly predict cardiovascular death and rehospitalization for HF in patients undergoing percutaneous repair of mitral valve insufficiency. Both markers might be useful components in new scoring systems to better predict short- and potentially long term mortality and morbidity after MitraClip procedure. PMID- 26368982 TI - Internal and external customers - the health service's heart. PMID- 26368984 TI - Child sex offences increase by more than a third. PMID- 26368983 TI - Babies to receive Men B vaccine. PMID- 26368985 TI - Half of children eat no veg. PMID- 26368986 TI - Young people at highest risk for STIs. PMID- 26368987 TI - Substance use higher in young offenders. PMID- 26368988 TI - New regulations aim to reduce liquitab ingestion. PMID- 26368989 TI - Healthy schools London: event report. PMID- 26368990 TI - Revalidation reality. PMID- 26368991 TI - School Health Matters: Teenagers want online health services. PMID- 26368992 TI - Best beginnings: From bump to baby. PMID- 26368993 TI - Supporting rehabilitation of traumatic brain injury sufferers in the community. PMID- 26368994 TI - The Tameside and Glossop Early Attachment Service: Meeting the emotional needs of parents and their babies. AB - Parent-infant emotional health is probably one of the most complex arenas in which mental health, maternity and health visiting services operate. This critical period can be highly emotionally charged, not only for the infant but also be for the parent. While most parents essentially get it right, severe ruptures in the parent-infant relationship can occur, and can have serious consequences. This paper describes a comprehensive and cost-effective parent infant mental health service based on a psychodynamic model. The service aims to meet the needs of all parents from those with a high level of need through to a universal provision. Strategic and theoretical underpinnings of the service model are described. PMID- 26368995 TI - Every child has the right to smile!--A qualitative study exploring barriers to dental registration in a SureStart area in Northern Ireland. AB - The aim of this research study was to explore parents' perceptions of factors influencing dental registrations of children, age birth to four years, living within a SureStart area. The electoral ward identified had the lowest rate of dental registrations for both the birth-two and three-five year age groups in a local healthcare Trust in Northern Ireland. The author chose to adopt a phenomenological approach to explore the lived experiences of parents in relation to dental behaviours. A purposive sample of eight parents currently known to SureStart services and not yet registered with a dentist was identified. Face-to face, semi-structured interviews were conducted. The interviewees were aged between 20-41 years and the number of children in the family ranged from one to three, with their age range spanning from one month to three years. The study identified inconsistencies in advice across professions, in relation to appropriate age of registration, resulting in children being denied early access to dental services. Childhood dental fears and anxiety have also had a lasting impact on some of the mothers which may influence their dental decision-making. PMID- 26368996 TI - Strong links for Public Mental Health. AB - The new, national Public Mental Health Network offers health visitors and school nurses an opportunity to gain more of a voice within policy. The Network is hosted by the Royal College of Psychiatrists and works closely with Public Health England and NHS England to improve population mental health and to prevent mental illness.The CPHVA, RCN and other professional bodies have a vital role to fill in shaping development of the Network, including sharing good practice, interprofessional education and innovative public health research. In the past, the public health community has often been slow and uncoordinated in responding to either grassroots needs or government imperatives. In particular, voices advocating for better mental health for children and families have not been heard. Trade Unionists know that solidarity amplifies the voice of individuals. My own interest as a professor is to build on all we know that makes families, schools, neighbourhoods (and groups of practitioners) more resilient--and capable of more and more. PMID- 26368997 TI - Last word with ... PROFESSOR JUDITH ELLIS. PMID- 26368998 TI - Peer Review Privilege Upheld in Michigan's Supreme Court. PMID- 26368999 TI - "Alone we can do so little, together so much". PMID- 26369000 TI - Critical Success Factors for a Successful EHR Implementation for Physicians Practices. PMID- 26369001 TI - Perspectives in Independent Practice. PMID- 26369002 TI - Remaining Independent: How Doctors in Private Practice are Adapting in the Changing Environment. PMID- 26369003 TI - Getting Ready for the 2015-16 Flu Season. PMID- 26369004 TI - Five Threats to Financial Independence. PMID- 26369005 TI - Ensuring Independent Practice is Here to Stay. PMID- 26369006 TI - Dietary protein quality evaluation in human nutrition. Report of an FAQ Expert Consultation. PMID- 26369007 TI - Polymeric Micelles as Novel Carriers for Poorly Soluble Drugs--A Review. AB - Polymeric micelles are used as 'smart drug carriers' for targeting certain areas of the body by making them stimuli-sensitive or by attachment of a specific ligand molecule onto their surface. The main aim of using polymeric micelles is to deliver the poorly water soluble drugs. Now-a-days they are used especially in the areas of cancer therapy also. In this article we have reviewed several aspects of polymeric micelles concerning their mechanism of formation, chemical nature, preparation and characterization techniques, and their applications in the areas of drug delivery. PMID- 26369008 TI - A Special Section on Nanophytomedicine. PMID- 26369009 TI - Low Doses of Traditional Nanophytomedicines for Clinical Treatment: Manufacturing Processes and Nonlinear Response Patterns. AB - The purpose of the present paper is to (a) summarize evidence for the nanoparticle nature and biological effects of traditional homeopathically prepared medicines at low and ultralow doses; (b) provide details of historically based homeopathic green manufacturing materials and methods, relating them to top down mechanical attrition and plant-based biosynthetic processes in modern nanotechnology; (c) outline the potential roles of nonlinear dose-responses and dynamical interactions with complex adaptive systems in generating endogenous amplification processes during low dose treatment. Possible mechanisms of low dose effects, for which there is evidence involving nanoparticles and/or homeopathically-manufactured medicines, include hormesis, time-dependent sensitization, and stochastic resonance. All of the proposed mechanisms depend upon endogenous nonlinear amplification processes in the recipient organism in interaction with the salient, albeit weak signal properties of the medicine. Conventional ligand-receptor mechanisms relevant to higher doses are less likely involved. Effects, especially for homeopathically-prepared nanophytomedicines, include bidirectional host state-dependent changes in function. Homeopathic clinicians report successful treatment of serious infections and cancers. Preclinical biological evidence is consistent with such claims. Controlled biological data on homeopathically-prepared medicines indicate modulation of gene expression and biological signaling pathways regulating cell cycles, immune reactions, and central nervous system function from studies on cells, animals, and human subjects. As a 200-year old system of traditional medicine used by millions of people worldwide, homeopathy offers a pulsed low dose treatment strategy and strong safety record to facilitate progress in translational nanomedicine with plants and other natural products. In turn, modern nanotechnology methods can improve homeopathic manufacturing procedures, characterize nanoparticle end-products, and describe interactions of homeopathic nanophytomedicines with living systems at the nanoparticle and even individual organism level of detection. Faster progress toward safe and effective personalized nanophytomedicine treatments can result. PMID- 26369010 TI - Curcumin-Loaded, Self-Assembled Aloevera Template for Superior Antioxidant Activity and Trans-Membrane Drug Release. AB - Fine combination of natural botanical extracts to evaluate and maximize their medicinal efficacy has been studied for long. However, their limited shelf-life, complicated extraction protocols, and difficult compositional analysis have always been a problem. It is due to this that such materials take time to convert them into a proper pharmaceutical technology or product. In this context, we report on synthesis of self-assembled template of one of the most popular natural product, aloevera. This forms a fine porous membrane like structure, in which a natural drug, curcumin has been immobilized/trapped. The so-made curcumin-loaded aloevera (CLA) structures have been carefully evaluated using Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), atomic force microscopy (AFM), UV-vis spectroscopy and fluorescence microscopy. While FTIR shows that there is no chemical interaction between aloevera and curcumin, the pores are finely occupied by curcumin molecules. Fine microscopy structures reveal their distribution and fluorescence microscopy confirm the presence of curcumin within the pores. TGA shows 15% loading of the curcumin in the template and UV-visible spectroscopy data shows independent peaks of both, aloevera (196 nm and 256 nm) and curcumin (423 nm), respectively. When subjected to antioxidant studies, using DPPH assays, CLAs show a synergistically superior DPPH radical scavenging activity as compared to only curcumin and only aloevera extract. Same is true for hydroxyl and NO2 radicals. Trans-membrane release study reveals that there is no significant difference in the amount of curcumin release from CLAs till initial 30 min, however, it increases steadily thereafter. CLA is found to facilitate efficient release of curcumin in 5 h, which is higher as compared to the curcumin alone. PMID- 26369011 TI - ZnO Nanoparticles-Red Sandalwood Conjugate: A Promising Anti-Diabetic Agent. AB - With the advances in nanoscience and nanotechnology the interest of researchers has expanded to interdisciplinary domain like bio-medical applications. Among such domains, one of the most important areas explored meticulously is the development of promising solutions in diabetes therapeutics. The disease associated with metabolic disorder, is one of the major challenges, due to its ever-increasing number of patients. The adverse effects of the synthetic enzymes like alpha-amylase and alpha-glucosidase inhibitors have invited many scientists to develop promising contender with minimal side-effects. On the other hand, Zinc has strong role in insulin synthesis, storage and secretion and thus its deficiency can be related to diabetes. In this context we have explored natural extract of Red Sandalwood (RSW) as a potent anti-diabetic agent, in conjugation with ZnO nanoparticles. ZnO nanoparticles have been synthesized via soft chemistry routes and duly characterized for their phase formation with the help of X-ray diffraction technique and Field-Emission Scanning Electron Microscopy. These monodispersed nanoparticles, -20 nm in size, were further conjugated to RSW extract. The conjugation chemistry was studied via Fourier transform infrared spectroscopy, UV-visible spectroscopy. Extract loading percentage was found from thermo-gravimetric analysis. 65% of the RSW extract was found conjugated to the ZnO nanoparticles. The anti-diabetic activity was assessed with the help of like alpha-amylase and alpha-glucosidase inhibition assay with murine pancreatic and small intestinal extracts. It was observed that the conjugated ZnO-RSW nanoparticles showed excellent activity against the crude murine pancreatic glucosidase as compared to the individual ZnO nanoparticles and the RSW extract. The ZnO-RSW conjugate showed 61.93% of inhibition while the bare ZnO nanoparticles and RSW showed 21.48% and 5.90% respectively. PMID- 26369012 TI - Biosynthesis of Gold Nanoparticles and Identification of Capping Agent Using Gas Chromatography-Mass Spectrometry and Matrix Assisted Laser Desorption Ionization Mass Spectrometry. AB - In the present study, gold nanoparticles (AuNPs) were synthesized using leaf extract of Syzygium jambolanum and capping agent has been explored. The synthesized AuNPs have been characterized using UV-visible spectroscopy (UV-vis), Fourier transform infrared spectroscopy (FTIR), high resolution transmission electron microscopy (HRTEM) and atomic force microscopic (AFM) analysis. The AuNPs show intense surface plasmon resonance (SPR) band at 528 nm and were found to be spherical and hexagonal in shape with particle size ranging from 20-30 nm. Transmission electron microscopy and atomic force microscopy were used to analyze the surface morphology of synthesized AuNPs. The capping ligand has been evaluated using matrix assisted laser desorption ionization-mass spectrometry (MALDI-MS) and gas chromatography-mass spectrometry (GC-MS) analysis. PMID- 26369013 TI - Novel Galactosylated Poly(ethylene glycol)-Cholesterol for Liposomes as a Drug Carrier for Hepatocyte-Targeting. AB - In this study, three types of galactosylated cholesterol (i.e., gal-PEG194-chol, gal-PEG1000-chol and gal-PEG2000-chol) were synthesized with one terminal of polyethylene glycol of various chain lengths conjugated to the galactoside moiety, and the other terminal conjugated to the cholesterol. The galactose modified liposomes were prepared by thin film-hydration method and doxorubicin (DOX) was loaded to the liposomes by using a ammonium sulfate gradient procedure. The liposomal formulations with galactosylated cholesterol were characterized. Flow cytometry and laser confocal scanning microscopy analyses showed that the galactose-modified liposomes facilitated the intracellular uptake of liposomes into HepG2 via asialoglycoprotein receptor (ASGP-R) mediated endocytosis. Cytotoxicity assay showed that the cell proliferation inhibition effect of galactose-modified liposomes was higher than that of the unmodified liposomes. Additionally, the study on frozen section of liver showed that the galactose modified liposomes enhanced the intracellular uptake of liposomes into hepatocytes. Taken together, these results suggested that liposomes containing such galactosylated cholesterol (i.e., gal-PEG-chol), had a great potential as drug delivery carriers for hepatocyte-selective targeting. PMID- 26369014 TI - Advancements and Avenues in Nanophytomedicines for Better Pharmacological Responses. AB - Novel drugs delivery systems (NDDS), formulations from plant actives and extracts are still a matter of thrust and hot cake among the researchers working with phytomedicine. Novel delivery systems such as polymeric liposomes, colloidisomes, aquasomes, ethosomes, niosomes, proliposomes, phytosomes, nanoparticles, nanocapsules, nanoemulsions, microsphere and transferosomes have been proven to be a better carrier for delivery of the phyto-constituents as already done by various eminent scientists. Due to increased bioavailability, protection from toxicity, enhancement of pharmacological activity, enhancement of stability, improved tissue macrophages distribution, sustained delivery, and protection from physical and chemical degradation novel delivery systems are more suitable delivery system in compare to the conventional systems. This articled, highlight the remarkable findings in the recent past by innovators exclusively working on novel drug delivery systems for phyto-constituents. PMID- 26369015 TI - New Approach to Prepare Willow Bark Extract-Lipid Based Nanosystems with Enhanced Antioxidant Activity. AB - In this study the conventional oils used for lipid nanocarriers (NLCs) synthesis were replaced by high concentration of fish oils (e.g., fish oil concentrated in omega-3 fatty acids, fish oil enriched in omega-3 and omega-6 fatty acids and salmon oil), in order to produce appropriate lipid based nanosystems able to entrap willow bark extract (WBE). Formulation factors such as the nature of the fish oil, glycerol content and WBE loading were evaluated to produce optimum lipid based nanosystems with suitable physical stability and enhanced antioxidant activity. The synthesized WBE-NLC showed spherical and homogeneous particles and average diameters in the range of 200-250 nm, as determined by TEM measurements. The electrokinetic potentials were negative for all free- and WBE-loaded NLCs, with values between -29.1 / - 35.8 mV, which reveal an excellent physical stability. By scanning calorimetry measurements it has been shown that the lipid crystallization and melting behavior of NLCs before and after loading with WBE were no significantly influenced by the type of fish oil used and only in a few NLCs formulations an obvious perturbation of lipid network have been detected. The chemiluminescence technique has been used to assess the effect of fish oil type on the in vitro antioxidant activity of WBE-NLCs. Ability of WBE entrapped within NLCs to scavange the free radicals was greater than for native WBE and fish oils. The difference between the antioxidant activity of WBE-NLC (98%) and those of pure WBE (AA% = 77.2) and fish oil (AA% = 83.7), may be explained by the occurrence of a synergistic effect between the components of lipid nanocarriers. PMID- 26369016 TI - Polyethylene Sebacate-Silymarin Nanoparticles with Enhanced Hepatoprotective Activity. AB - The present study evaluates role of pullulan as hepatic targeting agent. Nanoparticles of silymarin (SIM) a hepatoprotective drug were prepared using polyethylene sebacate (PES) as biodegradable polymer and surface modified with pullulan. PES-SIM nanoparticles (PES-SIM NP) and PES-SIM nanoparticles surface modified with pullulan (PES-SIM-PUL) were prepared by nanoprecipitation. Nanoparticles were evaluated for hepatoprotective activity in a model of carbon tetrachloride (CCl4) induced hepatotoxicity in rats. Pretreatment of rats with PES-SIM-NP and PES-SIM-PUL revealed reduced levels of SGOT, SGPT and ALKP compared to CCl4 treated group (p < 0.01) whereas levels of LPO and catalase were comparable to vehicle control suggesting enhanced hepatoprotection with nanoparticles. Histopathological evaluation of liver tissues also revealed better hepatoprotection with nanoparticles. Further significant decrease (p < 0.01) in levels of SGOT, SGPT and ALKP with difference PES-SIM-PUL than PES-SIM NP confirms the role of pullulan as hepatic targeting agent. PMID- 26369017 TI - Partially Acetylated Dendrimer-Entrapped Gold Nanoparticles with Reduced Cytotoxicity for Gene Delivery Applications. AB - Gene therapy has been concerned to be one of the most promising strategies to treat many diseases such as genetic disorders and cancer. However, design of safe and highly efficient gene delivery vectors still remains a great challenge. In this work, we report the use of partially acetylated dendrimer-entrapped gold nanoparticles (Au DENPs) for gene delivery applications. First, partially acetylated generation 5 poly(amidoamine) dendrimers with different acetylation degrees were used as templates to synthesize Au DENPs. The formed Au DENPs were characterized via different techniques and were used to complex two different pDNAs encoding luciferase (Luc) and enhanced green fluorescent protein (EGFP), respectively for gene transfection studies. The Au DENPs/pDNA polyplexes with different N/P ratios were characterized by gel retardation assay, dynamic light scattering, and zeta potential measurements, and the gene transfection efficiency was evaluated by Luc assay and fluorescence microscopic imaging of the EGFP expression, respectively. We show that despite the partial acetylation (5, 10, 20, and 30 acetyl groups per G5 dendrimer according to the molar feeding ratio), all acetylated Au DENPs are able to effectively compact the pDNA and transfect genes to the model cell line with high efficiency comparable to the Au DENPs without acetylation. With the proven less cytotoxicity of the partially acetylated Au DENPs than that of non-acetylated Au DENPs by cell viability assay, the developed partially acetylated Au DENPs may serve as promising vectors for safe gene delivery applications with non-compromised gene transfection efficiency. PMID- 26369018 TI - Improved Method for Preparing Cisplatin-Dendrimer Nanocomplex and Its Behavior Against NCI-H460 Lung Cancer Cell. AB - The effect of anticancer drugs could be significantly enhanced if it is encapsulated in drug delivery vehicles such as liposomes, polymers, dendrimers and other materials. For some conventional cisplatin encapsulating methods, however, suffers from low loading efficiency. Therefore, in order to overcome this limitation, in our study, sonication was used in preparation of the nanocomplex of a species of aquated cisplatin and carboxylated PAMAM dendrimer G3.5 to evaluate loading capacity as well as plantinum release behavior using FT IR, UV-Vis, NMR, ICP-AES, and TEM. The results show that 25.20 and 27.83 wt/wt% of cisplatin were loaded under stirring and sonication respectively, a remarkably improvement in loading efficiency compared to that of conventional method that used of cisplatin. In vitro study showed that this drug-nanocarrier complex also help reduce cisplatin's cytotoxicity but can still keep sufficient antiproliferative activity against lung cancer cell, NCI-H460, with IC50 at 0.985 +/- 0.01 MUM. PMID- 26369019 TI - Effective PEGylation of Fe3O4 Nanomicelles for In Vivo MR Imaging. AB - A practical and effective strategy for synthesizing PEGylated Fe3O4 nanomicelles is established. In this strategy, a magnetic fluid of the Fe3O4 nanomicelles was synthesized with amphiphilic PEGylated phospholipid as surfactant and soybean oil as stabilizer under simple mechanical stirring and subsequent ultrasonication. Transmission electron microscope (TEM) measurement indicated that the sample is monodisperse spherical Fe3O4 nanoparticles with internal core size of 9 nm and external nanomicelle shell thickness of 1.5 nm. The final hydrodynamic size of the sample is 19.5 nm and its zeta potential is - 38.5 mV, suggesting good stability of the magnetic nanomicelles in water. To assess the ability of magnetic nanomicelles to escape reticuloendothelial system (RES) uptake, in vitro cell phagocytosis experiments were conducted using murine macrophages (RAW264.7). The results indicated that the PEGylation can effectively prevent the uptake of the nanomicelles by the macrophages. Using a mouse model of 4T1 breast cancer, the nanomicelles provided a good magnetic resonance imaging (MRI) capability to sensitively detect tumor by enhanced permeability and retention (EPR) effect. The PEGylated monodisperse magnetic nanomicelles would become a potential contrast agent for passive targeting diagnosis of tumor by MR imaging. PMID- 26369020 TI - Facile Synthesis of Curcumin Nanocrystals and Validation of Its Antioxidant Activity Against Circulatory Toxicity in Wistar Rats. AB - Our investigation was carried out in two phases. First we synthesized curcumin nanocrystals using a simple precipitation method and characterized their absorbance, crystallinity, size, and morphology by UV-visible spectroscopy, X-ray diffraction (XRD) spectroscopy, High Resolution Transmission Electron Microscopy (HRTEM) and Particle size Analyzer (PSA), in comparison with bulk curcumin. Characterization studies revealed that the protocol we standardized resulted in Curcumin nanocrystals with 10-200 nm size which was fairly soluble in water in contrast to bulk curcumin. Due to its crystallinity, nanocurcumin that we synthesized was also referred as Curcumin Nanocrystals. In Phase 2, we have assessed the comparative antioxidant efficacy of Curcumin nanocrystals and bulk Curcumin in the circulation of 1,2-dimethyl hydrazine-treated rats by investigating lipid peroxidation, antioxidant enzymes (superoxide dismutase, catalase), GSH and GSH-dependent detoxification enzymes (glutathione peroxidase, gIutathione-S-transferase). Curcumin nanocrystals exerted its antioxidant effect by decreasing lipid peroxidation, and by enhancing the activities of antioxidant and detoxification enzymes studied. Curcumin nanocrystals exhibited its antioxidant action at 40 mg dose whereas the bulk curcumin exerted its effect at 80 mg dose. This may be due to enhanced solubility, dispersibility, and crystallinity of the nanocrystals, which might have enhanced its bioavailability when compared to poorly soluble bulk curcumin. PMID- 26369021 TI - Quantitation of Oxidative Stress Gene Expression in Human Cell Lines Treated with Water-Dispersible MnO Nanoparticles. AB - The objective of this study was to assess cytotoxicity of engineered MnO nanoparticles by quantifying the reactive oxygen species (ROS) related genes (glutathione S-transferase (GST) and catalase) using real time-polymerase chain reaction (RT-PCR) and molecular beacon (MB) technologies. Monodisperse MnO nanoparticles of 14 nm in size were synthesized by the encapsulation of polyethyleneglycol (PEG)-phospholipid shell around the MnO core to endow high water-dispersibility and biocompatibility. In vitro cytotoxicity was evaluated at different concentrations (10, 50 and 100 MUg/ml) and incubation times (12, 24 and 48 h) with human cancer cell lines (glioblastoma, lung adenocarcinoma and neuroblastoma cells). Both genetic and cellular cytotoxic screening methods produced consistent results, showing that GST and catalase ROS gene expression was maximized in 24 h incubation at 100 MUg/ml concentration of MnO nanoparticles for each cell line. However, the cytotoxicity effect of the PEG-phospholipid coated MnO nanoparticle was not significant compared with control experiments, demonstrating its high potential in the applications of nanomedicines for a diagnostic and therapeutic tool. PMID- 26369022 TI - The Dimension of Titania Nanotubes Influences Implant Success for Osteoclastogenesis and Osteogenesis Patients. AB - Implants that can inhibit osteoclastogenesis and enhance osteogenesis are desirable for osteoporosis patients. In this study, titania nanotube (Ti-NT) materials, having nanotube diameters of 30, 80, and 120 nm, were produced separately by anodization at 10, 40, and 60 V, respectively. The introduction of Ti-NTs to titanium substrates significantly reduced the formation and activity of osteoclasts on samples. With the enlargement of the nanotube diameter, the osteoclasts number, tartrate-resistant acid phosphatase staining and activity, and related gene expressions of osteoclasts were further reduced. Osteogenic ability was enhanced by increasing the nanotube diameter. Thus, larger-diameter nanotube implants, such as NT60, were better able to inhibit bone absorption and enhance bone formation to prevent implant loss and failure, especially for osteoporosis patients. PMID- 26369023 TI - Cytotoxicity Evaluation of pH-Controlled Antitumor Drug Release System of Titanium Dioxide Nanotubes. AB - Application of nanotechnology and nanomaterials in cancer therapeutics has attracted much attention in recent years. Nano titanium dioxide is one of the most important inorganic functional materials. Cellular toxicity of pH-controlled antitumor drug release system of titanium dioxide nanotubes (TiO2-NTs) in pancreatic cancer cells (SW1990) was evaluated in this paper. The anticancer drug, doxorubicin (DOX) was easily loaded on TiO2-NTs through adsorption forces because of its high specific surface area and perfect surface activity. The drug release from the nanotubes was pH dependent. The toxicological effects were studied after co-incubation of SW1990 with TiO2-NTs-DOX, TiO2-NTs and DOX, respectively. The cellular effect of DOX released from the TiO2-NTs-DOX was same as when DOX was used alone, indicating that the synthesized TiO2-NTs are well qualified as drug carriers in antitumor drug controlled-release system. PMID- 26369024 TI - Long-Circulating and pH-Sensitive Liposome Preparation Trapping a Radiotracer for Inflammation Site Detection. AB - Inflammatory and infectious diseases are one of the most common causes of mortality and morbidity. This paper aimed to prepare and to evaluate the ability of long-circulating and pH-sensitive liposomes, trapping a radiotracer, to identify inflamed focus. The physicochemical characterization of freeze-dried liposomes, using glucose as cryoprotectant, showed 80% of the vesicles with adequate mean diameter and good vesicle size homogeneity. Radiotracer encapsulation percentage in liposomes was 10.65%, of which 4.88% was adsorbed on the surface of the vesicles. Furthermore, liposomes presented positive zeta potential. Freeze-dried liposomes, stored for 180 days at 4 degrees C, did not show significant changes in the mean diameter, indicating good stability. Free radiotracer and radiolabeled liposomes were injected into inflammation focus bearing rats, and ex-vivo biodistribution studies and scintigraphic images were performed. Results showed that radiopharmaceutical, free and encapsulated into liposomes, were able to identify the inflamed site. Target/non-target ratios, obtained by scintigraphic images, were greater than 1.5 at all investigated times. Data did not show significant differences between the free radiotracer and radiolabeled liposomes. Results suggest that this liposomal preparation could be employed as an alternative procedure for inflamed site detection by means of scintigraphic images. However, as the radiotracer is adsorbed onto the liposome surface by electrostatic forces, it is suggested that a neutral radiopharmaceutical be used to confirm the potential of this formulation as a scintigraphic probe for inflammation/infection detection. PMID- 26369025 TI - Two Novel Nanosized Radiolabeled Analogues of Somatostatin for Neuroendocrine Tumor Imaging. AB - The somatostatin receptors (SR), which are overexpressed in a majority of neuroendocrine tumors, are targets for radiopeptide-based imaging using for example the 99mTc-Tyr3-Octreotide peptide. Dendrimers are hyperbranched polymeric structures. The nanoscopic size and near-monodisperse nature properties give polyamidoamine (PAMAM) dendrimers an edge over linear polymers in the context of drug delivery. Gold nanoparticles (AuNPs) conjugated to peptides produces stable multimeric systems with target-specific molecular recognition. The aim of this research was to prepare two nanosized multimeric systems for neuroendocrine tumor imaging, 99mTc-PAMAM-Tyr3-Octreotide and 99mTc-AuNP-Tyr-Octreotide, and to compare their in vitro uptake in SR-positive AR42J cancer cells as well as their biodistribution profile in athymic mice bearing AR42J tumors. [Tyr3, Lys(Boc)5] Octreotide was conjugated to the carboxylate groups of the PAMAM dendrimer (G3.5) with further Boc deprotection using TFA. 99mTc labeling was carried out by a direct method. 99mTc-Tyr3-Octreotide was conjugated to AuNPs (20 nm) by spontaneous reaction with the thiol group of cysteine. Radiochemical purity (RP) was determined by size-exclusion HPLC and ITLC-SG analyses. In vitro binding studies were carried out in AR42J cancer cells. Biodistribution studies were accomplished in athymic mice with AR42J-induced tumors with blocked and unblocked receptors. Elemental analysis demonstrated that 26 Tyr3-Octreotide molecules were successfully conjugated to one molecule of PAMAM. RP for both nanosized conjugates was > 94% and showed recognition for SR in AR42J cells. The tissue distribution of radioactivity 2 h after 99mTc-PAMAM-Tyr3-Octreotide administration in mice showed specific tumor uptake (4.12 +/- 0.57% of injected dose/g) and high accumulation in the pancreas (15.08 +/- 3.11% of injected dose/g) which expresses SR. No significant difference in the tumor uptake was found between 99mTc-PAMAM-Tyr3-Octreotide and 99mTc-AuNP-Tyr3-Octreotide. However, the dendrimer-peptide conjugate showed a significant renal excretion. Both radiopharmaceuticals demonstrated properties suitable for use as target specific agents for molecular imaging of tumors that overexpressed SR. PMID- 26369026 TI - Nanorings from Concatemeric DNA: Chemical Modification Drives Nanostructure Formation. AB - Self-assembly of DNA concatemers from native duplexes and those containing non nucleotidic bridges of varying polarity composed of repeating oligo(ethylene glycol) phosphates -O(CH2CH2O)(n)PO2- or alpha,Omega-alkanediol phosphates O(CH2)10OPO2(-)- units was compared. The structures obtained were characterised by polyacrylamide gel electrophoresis, enzymatic digestion and AFM. Our results have revealed that chemically-modified duplexes favour self-termination of concatemer growth and yield up to 35% of nanosized DNA rings. PMID- 26369027 TI - Mg-Doped Hydroxyapatite/Chitosan Composite Coated 316L Stainless Steel Implants for Biomedical Applications. AB - In this investigation, ultrasonication process was used for the synthesis of magnesium doped nano-hydroxyapatite (MH) (0, 1, 2, and 3 mol% of Mg concentration) particles with controlled size and surface morphology. The size of the prepared MH particles was in the range of 20-100 nm with narrow distribution. Increase in the concentration of Mg reduced the particle size distribution from 60 to 40 nm. On incorporation of Mg in HAp lattice, an increase of 20-66 nm in specific surface area was observed in microporous HAp particles. XRF and XRD patterns reveal that the particles possess stoichiometric composition with reduced crystallinity with respect to the Mg concentration. Surface morphology of MH/chitosan (CTS) coated implant was found to be uniform without any defects. The corrosion rate of the implant decreased with increase in Mg concentration. The in vitro formation of bonelike apatite layer on the surface of the MH/CTS coated implant was observed from simulated body fluid studies. The antimicrobial activity of the MH/CTS composites against gram-positive and gram-negative bacterial strains indicated that increasing Mg concentration enhanced antimicrobial properties. Nanoindentation analysis of apatite coated implant surface reveals that the mechanical property depends on the concentration of magnesium in HAp. From the cytotoxicity analysis against NIH 3T3 fibroblast, it was observed that the Mg incorporated HAp/CTS composite was less toxic than the MHO/CTS composite. From this result, it was concluded that the MH/CTS nanocomposites coated implant is the excellent material for implants. PMID- 26369028 TI - Preparation and Properties of Nano-Hydroxyapatite/Gelatin/Poly(vinyl alcohol) Composite Membrane. AB - In this study, the bone-like composite membrane based on blends of gelatin (Gel), nano-hydroxyapatite (n-HA) and poly(vinyl alcohol) (PVA) was fabricated by solvent casting and evaporation methods. The effect of n-HA content and the ratio of Gel/PVA on the properties of the composite was investigated. The Gel/PVA and n HA/Gel/PVA composite membranes were characterized by Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), water contact angle measurement and scanning electron microscopy (SEM). The mechanical properties of the composites were determined by tensile tests. The as prepared composite membranes exhibited hydrophobility, the water contact angle of composite membrane was 126.6 when its mass ratio of n-HA/Gel/PVA was 10/50/40. The tensile strength of composite membranes was greatly increased due to the introduction of n-HA, and the tensile strength was increased to 74.92 MPa when the mass ratio of n HA/Gel/PVA was 10/50/40. SEM observation indicated that n-HA was dispersed in the membranes and a sea-island structure was formed in the n-HA/Gel/PVA composite membranes, resulting in a significant increase in tensile strength. The as prepared n-HA/Gel/PVA composite membranes may be applied in the field of bone tissue engineering. PMID- 26369029 TI - Evaluation of Hemostatic Effects of Carbonized Hair-Loaded Poly(L-Lactic) Acid Nanofabrics. AB - Carbonized human hair is used to stop bleeding in traditional Chinese medicine. The present study was aimed to prepare a novel nanofiber containing carbonized human hair and evaluate its hemostatic effect. Carbonized human hair-loaded poly(L-lactic) acid nanofiber was prepared by electrospinning. The hemostatic efficacies of dressings composed of either carbonized human hair, carbonized human hair-loaded poly(L-lactic) acid nanofiber, Yunnan White Drug power or poly(L-lactic) acid nanofiber were investigated in several swine arterial and venous bleeding models. Blood loss and bleeding time were measured. In vitro, carbonized human hair, carbonized human hair-loaded nanofiber and Yunnan White Drug Powder significantly shortened the clotting time in comparison with the nanofiber control group. The hemostatic effects of the carbonized human hair-load nanofiber on liver and spleen traumatic wounds were better than those of carbonized human hair and Yunnan White Drug Powder in terms of blood loss and bleeding time. Similar effects were observed in swine femoral artery wound model. In the swine femoral vein wound model, bleeding could not be stopped in the control animals. In the carbonized human hair group, Yunnan White Drug Powder group and carbonized human hair-load nanofiber group, bleeding was stopped in 83.3%, 83.3% and 100% of the animals, respectively. In conclusion, dressing using carbonized human hair-load nanofibers is effective in controlling severe, uncontrolled bleeding. This dressing may offer a cheap alternative to dressings composed of coagulation proteins. PMID- 26369030 TI - Microemulsion Mediated Synthesis and Characterization of CdS Nanoparticles and Its Anti-Biofilm Efficacy Against Escherichia Coli ATCC 25922. AB - In this paper, we have reported the synthesize of CdS Nanoparticles through microemulsion mediated Triton X-100 neutral micelles at room temperature and its anti-biofilm activity against Escherichia coli. The encapsulated micelles nanoparticle system was studied for its absorption at 450 nm and emission spectrum was recorded peaking at 402 and 425 nm excited at 350 nm. The X-ray diffractive pattern (XRD) was confirmed the presence of cubic CdS crystallites. High resolution Transmission electron microscopy (HRTEM) reveals that the particles were spherical in shape and average size is 20 nm. Anti-biofilm activity of CdS nanoparticles were studied at 5 MUL and inhibition of growth of biofilm formed by Escherichia coli bacteria was documented by confocal laser scanning microscopy(CLSM) and confirmed that CdS nanoparticles in low concentration have very good anti-biofilm activity and hence may be used in antibacterial drug formulation. PMID- 26369031 TI - Development and Evaluation of Nanoemulsions Containing Phthalocyanines for Use in Photodynamic Cancer Therapy. AB - This work reports the development of oil in water (o/w) nanoemulsions containing poly(ethylene oxide)-poly(propylene oxide) block copolymer surfactant for the formulation of a delivery system for endovenous zinc and chloroaluminum phthalocyanines. A solubility study suggested clove oil and its combination with ethanol as the best candidates for the oil phase composition. The nanoemulsions were obtained using a high-pressure homogenizer and analyzed for droplet size to determine their short- and long-term stability. Formulations containing 7 and 10% oil phase and 12% surfactant presented higher stability and allowed the incorporation of a bigger amount of phthalocyanines in the formulation. Rheological analyses showed the prevailing Newtonian behavior of the nanoemulsions. Studies of toxicity and phototoxicity determined that the nanoemulsions produced were capable of inhibiting the growth of adenocarcinoma tumor cells. The nanoemulsions proved to be a good alternative for use in photodynamic therapy. PMID- 26369032 TI - Neurotoxicity of Silver Nanoparticles in Rat Brain After Intragastric Exposure. AB - It is known that the biological half-life of silver in the central nervous system is longer than in other organs. However, the potential toxicity of silver nanoparticles (NPs) on brain tissue and the underlying mechanism(s) of action are not well understood. In this study, neurotoxicity of silver NPs was examined in rat after intragastric administration. After a two-week exposure to low-dose (1 mg/kg, body weight) or high-dose (10 mg/kg) silver NPs, the pathological and ultrastructural changes in brain tissue were evaluated with H&E staining and transmission electron microscopy. The mRNA expression levels of key tight junction proteins of the blood-brain barrier (BBB) were analyzed by real-time RT PCR, and several inflammatory factors were assessed in blood using ELISA assay. We observed neuron shrinkage, cytoplasmic or foot swelling of astrocytes, and extra-vascular lymphocytes in silver NP exposure groups. The cadherin 1 (2( DeltaDeltaCt): 1.45-fold/control) and Claudin-1 (2(-DeltaDeltaCt): 2.77 fold/control) were slightly increase in mRNA expression levels, and IL-4 significantly increased after silver NP exposure. It was suggest that silver NP can induce neuronal degeneration and astrocyte swelling, even with a low-dose (1 mg/kg) oral exposure. One potential mechanism for the effects of silver NPs to the nervous cells is involved in inflammatory effects. PMID- 26369033 TI - Complexation of a 1-Indanone Thiosemicarbazone with Hydroxypropyl-beta Cyclodextrin Enhances Its Activity Against a Hepatitis C Virus Surrogate Model. AB - The current standard of care of the infection by hepatitis C virus (HCV) is effective in a limited number of patients and the high cost hinders therapy affordability and compliance. In this context, the research of new direct-acting antiviral agents (DAAs) for a more effective and long-lasting therapy is an urgent need and an area of active investigation. In an effort to develop novel DAAs, a series of 1-indanone thiosemicarbazones (TSCs) was synthesized and fully characterized. However, the high self-aggregation tendency and extremely poor aqueous solubility of these antiviral candidates often preclude their reliable biological evaluation in vitro. To maintain constant TSC concentrations over the biological assays, different TSC/cyclodextrin complexes were produced. In the present work, we report for the first time the cytotoxicity and antiviral activity of 5,6-dimethoxy TSC inclusion complexes with hydroxypropyl-beta cyclodextrin on bovine viral diarrhea virus (BVDV) as HCV surrogate model. Results showed a potent suppression of the virus replication, with greater activity for the inclusion complexes than the free compound. PMID- 26369034 TI - Transmission Electron Microscopy and Scanning Transmission X-Ray Microscopy Studies on the Bioaccumulation and Tissue Level Absorption of TiO2 Nanoparticles in Daphnia magna. AB - In this study, bioaccumulation and tissue-level absorption of TiO2 nanoparticles (NPs) in freshwater invertebrates were investigated using transmission electron microscopy (TEM) and scanning transmission X-ray microscopy (STXM). The TiO2 NPs were used to test impacts of core sizes (i.e., 5 +/- 2 nm and 23 +/- 7 nm for TiO2(SYN) and TiO2(P25), respectively) and agglomerations (i.e., well dispersed vs. highly agglomerated) on the uptake of TiO2 NPs in Daphnia magna (D. magna). Highly agglomerated TiO2 NPs, regardless of their core sizes, were heavily taken up into the digestive tract of D. magna and no detectable penetration of both TiO2 NPs into the gut epithelial cells of D. magna was observed in TEM and STXM images. However, significant damages involving morphological changes in the microvilli and gut epithelial cells (e.g., irregular shaped microvilli, epithelial cell protrusion, and dilatation of cytoplasmic inclusion) were observed only with the commercial TiO2 NPs (TiO2(P25)) with larger core size and mixed crystalline phase, while the laboratory synthesized TiO2 NPs (TiO2(Syn)) with smaller core size and single crystalline phase showed slight morphological changes in the gut microvilli and epithelial cells. In the case of D. magna exposed to the well dispersed synthetic TiO2 NP ((Cit)TiO2(Syn)), only a negligible amount of TiO2 NPs were found within the digestive tract of the D. magna without any significant damages in the gut microvilli and epithelial cells and any detectable penetrations of TiO2 NPs into epithelial cells of D. magna gut. These TEM and STXM observations confirmed us that uptake of NP into D. magna are strongly dependent on their agglomeration (i.e., hydrodynamic sizes), rather than their core sizes, while direct penetration of NPs into tissues of digestive tract seems unlikely without significant morphological changes (e.g., collapse of the epithelial tissue) caused by high toxicity of NPs or released metal ions. PMID- 26369035 TI - Promotion of Astragaloside IV for EA-hy926 Cell Proliferation and Angiogenic Activity via ERK1/2 Pathway. AB - The aim of this study was to determine the pro-angiogenic effects of Astragaloside IV (AS-IV) in vitro and reveal the potential mechanisms. A kind of human umbilical vein endothelial cells (HUVECs), named EA-hy926 cells, were treated with various dosages of AS-IV. We then utilized Cell Counting Kit-8 (CCK 8), real-time PCR and Western blot to detect EA-hy926 cells' proliferation and proangiogenic effect from AS-IV. Data showed that AS-IV promoted EA-hy926 cells proliferation, as assessed by CCK-8. The AS-IV was also associated with an increased tube formation and upregulation of vascular endothelial growth factor (VEGF) mRNA and protein in a dose-dependent manner. Interestingly, the influence of AS-IV on cell proliferation and angiogenisis could be abolished by inhibitor PD98059 through suppressed extracellular signal regulated protein kinases1/2 (ERK1/2) phosphorylation. These data demonstrated that the AS-IV activated the ERK1/2 pathway to control VEGF synthesis. Our findings conclude that the AS-IV promotes EA-hy926 cells proliferation and angiogenesis through ERK1/2 pathway, and it is also a regulator of VEGF. PMID- 26369036 TI - Crosslinked Electro-Spun Chitosan Nanofiber Mats with Cd(II) as Template Ions for Adsorption Applications. AB - The Cd(II) ion imprinting electro-spun crosslinked chitosan nanofiber mats were successfully prepared using Cd(II) as template ions and glutaraldehyde (GA) as crosslinker to investigate the adsorption of Cd(II) and Pb(II) ions in aqueous solutions. The Cd(II) ion imprinting electro-spun crosslinked chitosan nanofiber mats were characterized by the Fourier Transform Infrared Spectrometer (FTIR), Scanning Electron Microscope (SEM), Thermal Gravimetric Analysis (TGA), elemental analysis and solubility tests. The prepared chitosan nanofiber mats exhibited a higher adsorption capacity for both Cd(II) (364.3 mg/g) and Pb(II) (272.0 mg/g) ions. The dynamic study demonstrated that the adsorption process followed the second-order kinetic equation. Langmuir and Freundlich adsorption models were used to analyze the equilibrium isotherm data. The results showed that the Langmuir model was best suitable for predicting the adsorption isotherm of the studied system. The as prepared Cd(II) ion imprinting electro-spun crosslinked chitosan nanofiber mats might be used as an effective adsorbent for Cd(II) and Pb(II) removal from heavy metal wastewater. PMID- 26369037 TI - Effects of Nanofillers on the Thermo-Mechanical Properties and Chemical Resistivity of Epoxy Nanocomposites. AB - MWCNTs was synthesized using Ni-Cr/MgO by CVD method and were purified. The purified MWCNT was used as a filler material for the fabrication of epoxy nanocomposites. The epoxy nanocomposites with different amount (wt% = 0.5, 1.0, 2.0, 3.0, 4.0 and 5.0) of nanofillers (CB, SiO2 and MWCNTs) were prepared by casting method. The effects of nanofillers on the properties of neat epoxy matrix were well studied. The thermal properties of nanocomposites were studied using DSC, TGA and flame retardant, and also the mechanical properties such as tensile strength, flexural strength, compressive strength, impact strength, determination of hardness and chemical resistance were studied extensively. Based on the experiment's results, 2 wt% MWCNTs loading in epoxy resin showed the highest improvement in tensile strength, as compared to neat epoxy and to other epoxy systems (CB/epoxy, SiO2/epoxy). Improvements in tensile strength, glass transition temperature and decomposition temperature were observed by the addition of MWCNTs. The mechanical properties of the epoxy nanocomposites were improved due to the interfacial bonding between the MWCNTs and epoxy resin. Strain hardening behavior was higher for MWCNT/epoxy nanocomposites compared with CB/epoxy and SiO2/epoxy nanocomposites. The investigation of thermal and mechanical properties reveals that the incorporation of MWCNTs into the epoxy nanocomposites increases its thermal stability to a great extent. Discrete increase of glass transition temperature of nanocomposites is linearly dependent on MWCNTs content. Due to strong interfacial bonding between MWCNTs and epoxy resin, the chemical resistivity of MWCNT/epoxy nanocomposites is superior to neat epoxy and other epoxy systems. PMID- 26369038 TI - Effect of La3+ Impurity on Magnetic and Electrical Properties of Co-Cu-Cr-Fe Nanoparticles. AB - In this work a series of Co0.7Cu0.3Cr0.5La(x)Fe1.5-(x)O4 were synthesized via sol gel auto-combustion technique through the incorporation of La3+ into the raw powders. The structural magnetic and resistivity properties of the synthesized Co Cu-Cr-La ferrites were investigated. X-ray diffraction data indicated that, after La3+ doping, samples consisted of the main spinel phase in combination with a small amount of a foreign LaFeO3 phase. The addition of La3+ resulted in the reduction of particle size and an increase of porosity of the synthesized samples. The infrared spectra were recorded on the range from 300-800 cm(-1). The two primary bands corresponding to tetrahedral v1 at 595-605 cm(-1) and octahedral v2 at 389-413 cm(-1) were observed. The octahedral site radii increased rapidly with La3+ substitution while the tetrahedral site radii slowly increased. Deviation from the ideal oxygen positional parameter is found to decrease with La3+ substitution. The saturation magnetization of the samples decreased with the amount of La3+ ions doped and the coercivity shows an opposite trend. La3+ substitution affects the hopping between Fe2+ <-> Fe3+, resulted in increase in resistivity. PMID- 26369039 TI - Photoluminescence Quenching of CdTe Quantum Dots Generated via Glutathione-Capped Au Nanocrystals. AB - The photoluminescence (PL) quenching of thioglycolic acid (TGA)-capped CdTe quantum dots (QDs) by glutathione (GSH)-capped Au nanocrystals (NCs) were investigated via PL degradated measurement. It was found that the PL of the QDs with several sizes can be effectively quenched by GSH-Au NCs. The size and PL peak wavelengths of QDs have no significant impact on the quenching processing. Through the characterizations of UV-visble absorption spectrum, Zeta potential and steady-state, and time-resolved fluorescence spectroscopy, it was proved that the PL quenching of the QDs by GSH-Au NCs was attributed to static quenching caused by the formation of a QDs-Au complex. The binding parameters calculated from modified Stern-Volmer equation showed that the binding affinities between the GSH-Au NCs and CdTe QDs was in the order of 10(5) L x mol(-1), which indicated that the binding force was larger and the effective quenching occurred. The thermodynamic parameters studies revealed that the binding was characterized by positive enthalpy and positive entropy changes and hydrophobic force played a major role for QDs-Au association. In addition, all the quenching experiments were conducted in the phosphate-buffered saline (PBS) buffer solution at pH 7.4 and the investigation is expected to be applied in the biology. PMID- 26369040 TI - Structural, Morphological and Antibacterial Investigation of Ag-Impregnated Sol Gel-Derived 45S5 NanoBioglass Systems. AB - An increasing percentage of ageing population requires 30-year survivability of orthopedic devices that is not possible with the current bioinert materials, having a maximum of 15-year survivability. To satisfy this growing need, a shift is needed from replacement of tissues to regeneration of tissues. This is highly possible through the use of silica-bioactive glasses. However, a failure of implant can occur due to infections even by using such materials. Advances in using silver for antibacterial applications have been commercialized. However, higher concentrations of silver also lead to toxic effects. In this study, nanoBioglass 45S5 (NBG) and Ag-NBG were synthesized by using sol-gel method followed by solution-phase method, respectively. The bioactive crystals such as Na2Ca2Si3O9, CaCO3, and AgPO3, very much needed in the field of bone tissue engineering and in antibacterial strategies, were obtained in the NBG Matrix. The morphological investigation of NBG with 1 mM Ag+ concentrations shows the nanospikes arrangement of size 30-40 nm with spherical porous structure of size 10-20 nm, which supports the formation of collagen molecular fibrils on the surface of NBG matrices and enhances osseointegration. Both gram-positive and gram-negative strains show higher antibacterial activity for nanoBioglass with 1 mM Ag+ concentration. PMID- 26369041 TI - Synthesis, Characterization, and Gas-Sensing Properties of Mesoporous Nanocrystalline Sn(x)Ti(1-x)O2. AB - A nanocomposite mesoporous material composed by SnO2 and TiO2 with the size of -5 9 nm were prepared via a facile wet-chemical approach combining with an annealing process. The microstructure of obtained Sn(x)Ti(1-x)O2 powders were characterized by X-ray diffraction, X-ray Photo-electronic Spectroscopy, scanning electron microscope, transmission electron microscope and nitrogen adsorption-desorption experiment. The gas sensing performances to several gases of the mesoporous material were studied. The sensors of Sn(x)Ti(1-x)O2 (ST10, with 9.1% Ti) exhibited very high responses to volatile organic compounds at 160 degrees C. The order of the responses to volatile gases based on ST10 was ethanol > formaldehyde > acetone > toluene > benzene > methane. Sensor based on ST10 displays a highest sensitivity to hydrogen at 200 degrees C. Sensor responses to H2 at 200 degrees C have been measured and analyzed in a wide concentration range from 5 to 2000 ppm. The solid solution Sn(x)Ti(1-x)O2 can be served as a potential gas-sensing material for a broad range of future sensor applications. PMID- 26369042 TI - Synthesis and Luminescence Properties of Terbium-Doped Lanthanum Oxychloride Nanostructures. AB - LaOCl:Tb3+ nanofibers, nanotubes and nanobelts were prepared via electrospinning combined with a double-crucible chlorination technique using NH4Cl powders as chlorinating agent. Different morphologies of LaOCl:Tb3+ nanostructures were obtained through adjusting some of the electrospun parameters. The as-prepared LaOCl:Tb3+ nanostructures are tetragonal in structure with space group of P4/nmm. The diameters of LaOCl:Tb3+ nanofibers, nanotubes and the width of LaOCl:Tb3+ nanobelts are respectively 133.99 +/- 16.95 nm, 140.57 +/- 17.82 nm and 5.32 +/- 0.63 MUm under the 95% confidence level. Under the excitation of 230-nm ultraviolet light, the LaOCl:Tb3+ nanostructures emit the predominant emission peaks at 544 nm originated from the energy levels transition of 5D4 --> 7F5 of Tb3+ ions. The optimum molar percentage of Tb3+ in the LaOCl:Tb3+ nanofibers is 7%. LaOCl:Tb3+ nanobelts exhibit the strongest PL intensity of the three nanostructures under the same doping molar concentration. The possible formation mechanisms of LaOCl:Tb3+ nanostructures are also proposed. PMID- 26369043 TI - Morphology Dependent Photocatalytic Activity of alpha-MoO3 Nanostructures Towards Mutagenic Acridine Orange Dye. AB - The morphological evolutions of orthorhombic molybdenum oxide nanostructures with high crystalline nature have been successfully synthesized by combining low temperature sol-gel and annealing processes. Strong influence of gelation temperature is a factor facilitated to control the material morphology. Morphological transformations like nanospheres, nanoplatelets, mixtures of hexagonal platelets, and one-dimensional nanobars were obtained. The possible morphological formation mechanism has been proposed as a self-assemble process of nucleation and a mechanism for particle growth by Ostwald ripening. The as prepared nanostructures were recognized as photocatalysts for the degradation of Acridine Orange under Ultra Violet light. The obtained mixed morphology (hexagonal nanoplatelets and nanobars) showed a high photocatalytic property to degrade mutagenic Acridine Orange dye. Moreover, they could be easily recycled without changing the photocatalytic activity due to their 1-Dimensional and 2 Dimensional nanostructure property. PMID- 26369044 TI - One-Pot Synthesis of Multipod ZnO-Carbon Nanotube-Reduced Graphene Oxide Composites with High Performance in Photocatalysis. AB - Multipod ZnO-multi-walled carbon nanotube (MWCNT)-reduced graphene oxide (RGO) ternary nanocomposites were synthesized via a simple one-pot hydrothermal process using graphene oxide (GO)-dispersed MWCNT and zinc nitrate as raw materials. Scanning electron microscopy analysis indicated the formation of multipod structure of ZnO in the presence of MWCNT. XRD confirmed that the ZnO multipod was in a hexagonal phase while UV-vis and FTIR spectroscopy confirmed that the graphene oxide in the resulting material was in the reduced form. The as-prepared MWCNT-RGO-ZnO composites displayed excellent photocatalytic performance towards the degradation of methylene blue. More specifically, the degradation rate constant of using MWCNT-RGO-ZnO composites were twice and thrice higher than those of using RGO-ZnO composites and bare ZnO material, respectively. The main reason of enhanced photocatalytic property might be due to the internal stepwise energy level of the three components, which helped the electron separation and hinder the charge recombination. PMID- 26369045 TI - Synthesis and Characterization of Cobalt/Palladium Multilayer Film and Nanodiscs on Polyethylene Terephthalate Substrate. AB - Cobalt/Palladium (Co/Pd) multilayer film and nanodisc samples were fabricated on polyethylene terephthalate (PET) substrates. The effects of surface roughness and grain size of PET substrate, the Co/Pd layer and the Au intermediate layer on the magnetic properties of these samples were investigated. We observed that the coercivity for Co/Pd films deposited directly on a smoother PET substrate is significantly smaller when compared with Co/Pd films deposited at the same time on Au buffer layer. The patterned Co/Pd nanodisc array exhibited a larger coercivity than the corresponding continuous film due to lower probability of finding nucleation sites in reduced film area. PMID- 26369046 TI - Effect of Shell Growth and Doping Conditions of Core-Shell Homojunction Si Nanowire Solar Cells. AB - Effects of shell growth and doping conditions on the structural, optical and photovoltaic properties of core-shell homojunction Si nanowire (SiNW) arrays have been investigated. Core-shell nanowires were fabricated using a combination of metal-catalyzed electroless etching (MCEE) and thermal chemical vapor deposition (CVD) techniques. SiNWs formed by MCEE technique readily bundles with each other, disturbing the formation of radial p-n junctions surrounding them. CVD has made it possible to form uniform p-type Si shell layers on n-type SiNWs formed by MCEE technique. Results of SEM and Raman measurements reveal that electrical active B concentration can be increased with increase of shell thickness by increasing doping gas fluxes and growth time while keeping good crystallinity. Reflectivity measurements show an increase of light reflection in the visible range with increasing shell thickness. The short circuit current (I(sc)) and fill factor (FF) closely depend on the shell growth time and the dopant gas flux for the growth of shell layers. These results show doping conditions to be a key parameter for core-shell homojunction SiNW solar cells. PMID- 26369047 TI - Influence of Various Solvents on the Luminescent Performance of 1,8-Naphthalic Anhydride Modified by Eu3+ Ions. AB - Eu(3+)-modified 1,8-naphthalic anhydride (ENC) as a fluorescent tracer was successfully prepared, and then the effects of various solvents, including DMF, DMSO, CH3OH, C2H3N, and C3H6O, on the fluorescent performances of obtained ENC were investigated by means of Ultraviolet-visible absorption, Photoluminescence performances, Fourier transform infrared spectroscopy, Thermogravimetric analysis, and Time-resolved fluorescence measurements. The results showed that the inductive force strength derived from Eu3+ ion was gradually decreased with increasing polarity of used solvents as in order: C3H6O < C2H3N < DMF < CH3OH < DMSO, while the co-effects of various solvents involving hydrogen bonding were increased. Meanwhile, the influences of mentioned-above interactions on the luminescence features of resultant ENC were remarkable, which demonstrated the gradual decreasing of fluorescent intensity of characteristic peaks by accompany with obvious red-shifting of their emission wavelength. Furthermore, the fluorescence decay behaviors of ENC were elucidated, and therefore its luminescence mechanism was put forward. PMID- 26369048 TI - Synthesis, Optical and Electrochemical Properties of Y2O3 Nanoparticles Prepared by Co-Precipitation Method. AB - Y2O3 nanoparticles were synthesized by co-precipitation route using yttrium nitrate hexahydrate and ammonium hydroxide as precursors. The prepared sample was calcined at 500 degrees C and subjected to various characterization studies like thermal analysis (TG/DTA), X-ray diffraction (XRD), transmission electron microscope (TEM), UV-visible (UV-Vis) and photoluminescence (PL) spectroscopy. The XRD pattern showed the cubic fluorite structure of Y2O3 without any impurity peaks, revealing high purity of the prepared sample. TEM images revealed that the calcined Y2O3 nanoparticles consist of spherical-like morphology with an average particle size of 12 nm. The absorption spectrum of calcined samples shows blue shift compared to the as-prepared sample, which was further confirmed by PL studies. The possible formation mechanism of Y2O3 nanoparticles has been discussed based on the experimental results. Electrochemical behavior of Y2O3 nanoparticles was studied by cyclic voltammetry to assess their suitability for supercapacitor applications. PMID- 26369049 TI - One-Pot Low Temperature Synthesis and Characterization Studies of Nanocrystalline alpha-Fe2O3 Based Dye Sensitized Solar Cells. AB - Dye-sensitized solar cell (DSSC) based alpha-Fe2O3 nanostructures with two different morphologies, such as nanorods (FeONRs) and nanoparticles (FeONPs), were synthesized by one-pot low temperature method. The crystal structure and phase purity of the as-prepared samples were characterized by X-ray powder diffraction (XRD) and further determined by Rietveld refinements XRD analysis. The average crystallite size was calculated using Debye Sherrer formula, and it shows the range of 9.43-26.56 nm. The morphologies of the products were studied by high resolution scanning electron microscopy (HR-SEM) and it was confirmed by high resolution transmission electron microscopy (HR-TEM). The formation of pure alpha-Fe2O3 samples was further confirmed by energy dispersive X-ray (EDX) analysis. The optical properties and the band gap energy (E(g)) were measured by UV-Visible diffuse reflectance spectra (DRS) and photoluminescence (PL) spectra. The band gap energy was measured using Kubelka-Munk method, and the values are decreased from 2.36 eV to 2.21 eV as the temperature increased from 300 to 400 degrees C with increasing the crystallite size. Magnetic hysteresis (M-H) loop revealed that the as-prepared alpha-Fe2O3 samples displayed ferromagnetic behavior. FeONRs sample shows higher saturation magnetization (M(s)) value (40.21 emu/g) than FeONPs sample (23.06 emu/g). The dye-sensitized solar cell based on the optimized FeONRs array reaches a conversion efficiency of 0.43%, which is higher than that obtained from FeONPs (0.29%) under the light radiation of 1000 W/m2. PMID- 26369050 TI - Wireless Falling Detection System Based on Community. AB - The elderly are more likely to suffer the aches or pains from the accidental falls, and both the physiology and psychology of patients would subject to a long term disturbance, especially when the emergency treatment was not given timely and properly. Although many methods and devices have been developed creatively and shown their efficiency in experiments, few of them are suitable for commercial applications routinely. Here, we design a wearable falling detector as a mobile terminal, and utilize the wireless technology to transfer and monitor the activity data of the host in a relatively small community. With the help of the accelerometer sensor and the Google Mapping service, information of the location and the activity data will be send to the remote server for the downstream processing. The experimental result has shown that SA (Sum-vector of all axes) value of 2.5 g is the threshold value to distinguish the falling from other activities. A three-stage detection algorithm was adopted to increase the accuracy of the real alarm, and the accuracy rate of our system was more than 95%. With the further improvement, the falling detecting device which is low cost, accurate and user-friendly would become more and more common in everyday life. PMID- 26369051 TI - Facile Fabrication of AgCl Nanoparticles and Their Application in Adsorptive Desulfurization. AB - Adsorption via pi-complexation is highly promising for selective removal of aromatic sulfur from transportation fuels. Because adsorbents play a crucial role in the process of desulfurization, the development of efficient adsorbents attracts increasing attention recently. In the present study, AgCl nanoparticles were employed as pi-complexation adsorbents for adsorptive desulfurization, for the first time. A facile strategy for the fabrication of AgCI nanoparticles was designed in aqueous phase with the assistance of surfactant (namely, cetyltrimethylammonium chloride). The present strategy avoids the use of cosurfactant and oil phase that is compulsory for the traditional microemulsion method. As a result, the synthetic system is greatly simplified and the synthetic controllability is improved. By adjusting the reaction temperature, both size and morphology of AgCl nanoparticles can be well controlled. We also demonstrate that the obtained AgCI nanoparticles are active in adsorptive desulfurization, and the adsorption capacity can be well correlated with the particle size of AgCl. The high accessibility of active Ag(I) sites in AgCl nanoparticles is believed to be responsible for the good adsorptive desulfurization capacity. The present study may open a way for the development of new, efficient adsorbents based on nanoparticles. PMID- 26369052 TI - Preparation and Characterization of Graphene/Fe3O4 Composites by Solvothermal Method. AB - In the present study, graphene/Fe3O4 nanocomposites were prepared by solvothermal method using graphite oxide (GO) and FeCl3 x 6H2O as starting materials and the products were characterized by X-ray Diffraction (XRD), Scanning Electronic Microscope (SEM) and Vibrating Sample Magnetometer (VSM). Effects of Fe ion concentration, temperature and time of solvothermal reaction on the magnetic properties, microstructures and morphologies of graphene/Fe3O4 nanocomposites were investigated. The results showed that with the raising of Fe ion, particle size of the products became bigger, and saturation magnetization of the products got higher. The saturation magnetization and particle size of the products can be enhanced by increasing the reaction time and temperature, but the change of saturation magnetization and particle size were not obvious after the time got 8 h and temperature was at 200 degrees C, which demonstrated that the products became stable under this condition. The morphologies, microstructures and properties of products can be controlled by adjusting synthesis conditions. PMID- 26369053 TI - Controllable Synthesis and Photocatalytic Properties Study of Na2Ti3O7 and H2Ti3O7 Nanotubes with High Exposed Facet (010). AB - The role of replacing Na+ with H+ of titanate in promoting photocatalytic performance was investigated. The experimental results showed that H2Ti3O7 and Na2Ti3O7 catalysts with the same high exposed (010) facet had the similar light absorption capacity, TiO6 octahedral structure, and specific surface area. By comparing to Na2Ti3O7, H2Ti3O7 had longer lifetime and higher separation efficiency of the photo-generated electron-hole pairs, and also had higher density of surface oxygen vacancies, which resulted in the excellent performances for photocatalytic hydrogen production and dye degradation reactions. PMID- 26369054 TI - Effect of Surfactants on Electrochemical Properties of Vanadium-Pentoxide Nanoparticles Synthesized via Hydrothermal Method. AB - Vanadium pentoxide (V2O5) nanoparticles were synthesized via an anionic, cationic and non-ionic surfactant assisted hydrothermal method in which Ammonium metavanadate (NH4VO3) was used as precursor. The synthesized nanoparticles were characterized by using powder X-Ray Diffractometer, Scanning Electron Microscopy and UV-Vis spectroscopy. Crystalline nanoparticles were formed using different surfactants like Sodium Dodecyl Sulphate (SDS), Cetyltrimethylammonium Bromide (CTAB), Polyvenylpyrollidone (PVP) and Sodium Dodecyl Benzene Sulfonate (SDBS). The specific capacitance of V2O5 was calculated in 0.5 M KCl and 0.5 M Na2SO4 aqueous electrolyte by using cyclic voltammetry (CV). Electrochemical impedance, and Chronocoulommetry studies revealed a good capacitive and charge-discharge behavior of the prepared V2O5, which is very promising for the application for next-generation high-performance electro-chemical supercapacitors. PMID- 26369055 TI - Analysis of Resistance and Surface Recombination Velocities by Contact Coverage for Optimizing Electrical Loss in c-Si Local Back Contact. AB - Recently, the importance of solar cell research has emerged due to emerging social issues such as environmental pollution problems and rising oil prices. Accordingly, each company is studying to make solar cell of high efficiency. In order to fabricate high-efficiency solar cells, the two major techniques have to be applied on the rear. One is complete passivation of the surface using a thermal oxide and the other one is the part that comes in contact with the electrode doped partially LBSF (Local BSF) formation. In this paper, LBC technology which is usually applied for high efficiency crystalline silicon solar cell, applied to mass productive solar cell to achieve high open circuit voltage and short circuit current with low surface recombination from rear side. Thermal SiO2/SiN(x) double layer which has superior thermal stability is formed on rear surface as passivation layer, then 1% of the whole rear surface area is locally contacted with aluminum. Finally, the cell has been fired at high temperature and the cell process has complete. The fabricated LBC cells conversion efficiency was 18.0% with 625 mV of open-circuit voltage (V(oc)), 37.58 mA/cm2 of current density (J(sc)), 76.3% of fillfactor (FF) at 5% contact coverage, respectively. PMID- 26369056 TI - Preparation of Gold-Silver Alloy Nanoparticles Supported on NiCo2O4 Spinel Oxides for the Treatment of CO in Atmosphere. AB - Heterometallics are an important class of catalysts. Alloy nanoparticles have higher activities than monometallic counterparts in catalysis because of the synergistic effects between the two metals. The Ni-Co composition, which is a typical alloy chemical composition, has a remarkable effect on catalytic activity. Ni-Co mixed oxides were characterized by thermal effect, X-ray diffraction, energy dispersive X-ray spectroscopy, Scanning Electron Microscope and BET specific surface area techniques. X-ray diffraction show that the formation of small spinel oxides nanoparticles. Very small amounts of gold-silver alloy nanoparticles deposited on such mixed oxides improve the catalytical activity for CO oxidation. PMID- 26369057 TI - Preparation of Copper Sulfide Nanoparticles by Sonochemical Method and Study on Their Electrochemical Properties. AB - Copper sulfide (CuS) nanoparticles have been prepared by a facile sonochemical method using copper nitrate and thiourea as precursors. The X-ray diffraction analysis revealed the formation of hexagonal CuS. The Field-emission scanning electron microscope showed the formation of CuS nanoparticles with size in the range of 50 nm. Moreover, the electrochemical properties of the prepared CuS nanoparticles are examined by the use of cyclic voltammetry and electrochemical impedance spectroscopy. The cyclic voltammetry studies show a maximum specific capacitance of about 62.77 F/g at a 5 mV s(-1) scan rate. The electrochemical impedance studies such as Nyquist and Bode plots suggested that the pseudocapacitive properties of the prepared CuS nanoparticles. PMID- 26369058 TI - Simulation Studies of InGaN Based Light-Emitting Diodes to Reduce Electron Overflow Problem by Designing Electron Blocking Layer. AB - InGaN/GaN-based Multi Quantum Well light-emitting diodes (MQW LEDs) with p AlInGaN/AlGaN electron blocking layers are studied using the SimuLED simulation software for analysing the electron leakage problem. The simulation results specify the importance of p-AlInGaN/AlGaN electron blocking layers (EBL) to improve the optical and electrical performance of the LED device structure. The designed cascade AlInGaN layer in AlInGaN/AlGaN EBL was investigated by changing different Al and In concentrations and was analysed. It shows an increase in Internal Quantum Efficiency by insertion of Al(x)In(y)Ga(1-x-y)N-Al0.15Ga0.85N(X = 0.1, Y = 0.15) EBL instead of conventional AlGaN EBL. Structure shows an increasing carrier capture within active region with minimizing carrier leakage and a significant reduction in efficiency droop. The suppression in Efficiency droop phenomenon can be attributed to p-AlInGaN/AlGaN electron blocking layers which aiding a supportive barrier for electron overflow and thereby enhancing the electron blocking efficiency. PMID- 26369059 TI - Influence of Photoactive Layer Structure on Device Performance of Poly(2-methoxy 5-(2-ethylhexyloxy)- 1,4-phenylene vinylene)-CuInS2/ZnO Solar Cells. AB - This paper reported ternary MEH-PPV-CuInS2/ZnO solar cells, which were fabricated with the mixture of poly(2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylene vinylene) (MEH-PPV) and CuInS2 quantum dots (QDs) as photovoltaic layer and ZnO nanorod arrays (ZnO-NAs) as electron acceptor. The effects of photoactive layer structure (e.g., the change of spinning rate, thermal annealing temperature, annealing order and annealing method) on device performance are observed, and devices are measured by steady current-voltage (J-V) curve under the monochromic illumination at 470 nm. Results showed that the spinning rate of photoactive layer at 2000 rpm obtained the optimum thickness, moreover, solvent annealing firstly then the deposition of the positive electrode, finally thermal annealing at 140 degrees C contributing to the better reorganization for polymer and CuInS2 QDs to form the more stable phase-segregated state in the photovoltaic layer in the MEH-PPV CuInS2/ZnO-NAs solar cells, obtaining the maximum power conversion efficiency of 2.54% under the monochromic illumination at 470 nm. PMID- 26369060 TI - Observation of Room Temperature Ferromagnetism in InN Nanostructures. AB - The room temperature ferromagnetic behavior of InN nanostructures grown by molecular beam epitaxy (MBE) is explored by means of magnetization measurements. The saturation magnetization and remanent magnetization are found to be strongly dependent on the size of the nanostructures. This suggests that the ferromagnetism is essentially confined to the surface of the nanostructures due to the possible defects. Raman spectroscopy shows the existence of indium vacancies which could be the source of ferromagnetic ordering in InN nanostructures. PMID- 26369061 TI - The Role of Oxygen Vacancies on Switching Characteristics of TiO(x) Resistive Memories. AB - Using oxygen vacancy rich (VO-rich) TiO(x) dielectric with high work function Ni electrode, large resistance window of > 10x and narrow current distribution were realized in the Ni/VO-rich TiO(x)/TaN resistive random access memory (RRAM) device. It can be ascribed to the formation and rupture of conducting filaments by the percolation of VOs and Ti interstitials. Moreover, the effects of annealing treatment and top electrode on resistive switching properties were investigated. The device with VO-deficient TiO(x) after annealing reduces the defects and exhibits small window and low switching currents. The device with low work function Ti top electrode provides low barrier to increase reset currents and the randomly distributed filamentary paths forms near the Ti causes wide current distribution. PMID- 26369062 TI - Synthesis of Novel Sea-Urchin-Like CdS and Their Optical Properties. AB - A novel morphology of CdS sea-urchin-like microstructures is synthesized by simple thermal evaporation process. Microstructures with average size of 20-50 MUm are composed of single crystalline CdS nanobelts. The structural, compositional, morphological characterization of the product were examined by X ray diffraction, energy dispersive X-ray spectroscopy, Raman spectroscopy, scanning electron microscope, transmission electron microscopy and selected area electron diffraction while optical properties are investigated by Photoluminescence spectroscopy and time-resolved Photoluminescence measurements. The tentative growth mechanism for the growth of sea-urchin-like CdS is proposed and described briefly. A strong green emission with a maximum around 517 nm was observed from the individual CdS microstructure at room temperature, which was attributed to band-edge emission of CdS. These Novel structures exhibit excellent lasing (stimulated emission) with low threshold (9.07 MUJ cm(-2)) at room temperature. We analyze the physical mechanism of stimulated emission. These results are important in the design of green luminescence, low-threshold laser and display devices in the future. PMID- 26369063 TI - Synthesis and Optical Properties of CdTe(x)Se(1-x)-Based Red to Near-Infrared Emitting Quantum Dots. AB - A series of red to near-infrared (NIR) emitting quantum dots (QDs) with spherical morphologies and tunable photoluminescence (PL) properties have been synthesized by a facile organic route using octadecene (ODE) as solvent and oleic acid (OA) as single capping agent. CdSe cores with the average size of 4.5 nm display the typical optical behaviors with the PL emission peak around 610 nm. The coating CdZnS shells are introduced on the surface of CdSe cores for improving the photostability and PL efficiency of the initial QDs. As the thickness of CdZnS shells increasing, the gradual red-shift of emission wavelength varying from 617 to 634 nm of the resulting QDs can be observed, along with the remarkable increase of PL quantum yield (QY). The composition-dependent CdTe(x)Se(1-x) (CdTeSe) cores with the emission in NIR region are easily carried out by adjusting the molar ratio of Se/Te. The abnormal variation of optical bowling effect is mainly ascribed to the composition effect of alloyed QDs. Compared with CdTe0.1Se0.9/CdZnS core/shell QDs, the introducing of CdZnS shells on CdTe0.05Se0.95 cores can exhibit better passivation effect on surface status, consequently leading to the red-shifted emission peaks in the range of 739-752 nm with the maximum PL QY reaching up to 45.09%. The unique PL properties of CdTeSe based QDs in the red to NIR range make these core/shell QDs attractive for future biological sensing and labeling applications. PMID- 26369064 TI - Facile One-Step Fabrication of Ordered Ultra-Long Organic Microwires Film for Flexible Near-Infrared Photodetectors. AB - Micro/nanoscale electronic devices, such as transistors and sensors, made from single-crystalline organic micro/nano-structures with tunable molecular/structural design are much smaller and more versatile than those that rely on conventional polycrystalline/amorphous organic films, but their development for mass production has been thwarted by difficulties in aligning and integrating the organic crystals required. Here, we developed an improved evaporation induced self-assemble method to accomplish large-area uniform growth of ultra-long methyl-squarylium (MeSq) microwires (MWs) films. The MWs could align along the dewetting direction of the solution with length over the entire substrate, thus lessening the requirement for precisely addressing the positions of MWs. Near infrared (NIR) photodetectors based on the ordered organic MWs film were directly constructed on Si/SiO2 substrate. The MeSq MWs showed high sensitivity to the NIR light with excellent stability and repeatability. To evaluate the potential applications of the organic MWs film in flexible and transparent electronics, flexible photodetectors were constructed by transferring the MWs film to polydimethylsiloxane (PDMS) substrate. Significantly, the device showed good flexibility and could stand a large bending stress due to the superior mechanical flexibility of the organic MWs. This characteristic opens new prospects for the applications of the MeSq MWs. PMID- 26369065 TI - The Oxidation Behaviour of Diamond Like Carbon for Phase-Change Probe Memory Application. AB - Phase-change probe memory, as a promising candidate for next-generation storage device, usually requires a capping layer to protect phase-change media from wear and corrosion. Diamond-like carbon film has been commonly used for capping layer due to its high mechanical hardness and easiness for tailoring physical properties. However, the possibility for such carbon thin film to react to surrounding oxygen when subjected to Joule heating during the recording process of phase-change probe memory is rarely investigated before from both experimental and simulation point of view. Therefore, a novel carbon oxidation model was developed to mimic the chemical reaction of carbon film to the surrounding oxygen in terms of the degradation of layer thickness. Results obtained from this model are in a good agreement with the experimental counterpart, indicating the physical reality of this proposed model. PMID- 26369066 TI - Photodegradation of Mercaptopropionic Acid- and Thioglycollic Acid-Capped CdTe Quantum Dots in Buffer Solutions. AB - CdTe quantum dots (QDs) were synthesized by 3-mercaptopropionic acid (MPA) and thioglycollic acid (TGA) as capping agents. It is confirmed that TGA and MPA molecules were attached on the surface of the QDs using Fourier transform infrared (FT-IR) spectra. The movement of the QDs in agarose gel electrophoresis indicated that MPA-capped CdTe QDs had small hydrodynamic diameter. The photoluminescence (PL) intensity of TGA-capped QDs is higher than that of MPA capped QDs at same QD concentration because of the surface passivation of TGA. To systemically investigate the photodegradation, CdTe QDs with various PL peak wavelengths were dispersed in phosphate buffered saline (PBS) and Tris-borate ethylenediaminetetraacetic acid (TBE) buffer solutions. It was found that the PL intensity of the QDs in PBS decreased with time. The PL peak wavelengths of the QDs in PBS solutions remained unchanged. As for TGA-capped CdTe QDs, the results of PL peak wavelengths in TBE buffer solutions indicated that S(2-) released by TGA attached to Cd(2+) and formed CdS-like clusters layer on the surface of aqueous CdTe QDs. In addition, the number of TGA on the CdTe QDs surface was more than that of MPA. When the QDs were added to buffer solutions, agents were removed from the surface of CdTe QDs, which decreased the passivation of agents thus resulted in photodegradation of CdTe QDs in buffer solutions. PMID- 26369067 TI - Conformational Flexibility and pH Effects on Anisotropic Growth of Sheet-Like Assembly of Amphiphilic Peptides. AB - Peptide-based biomaterials have many potential applications in tissue engineering, drug delivery, surface engineering, and other areas. In this study, we exploited a series of amphiphilic diblock model peptides (L5K10, L5GSIIK10, and L5P(D)PK10) to understand how the supramolecular assembly morphology may be modulated by the physical properties of the peptide monomer and experimental conditions. A combination of experimentation and simulation revealed that although all three peptides lack stable structures as monomers, their levels of conformational heterogeneity differ significantly. Importantly, such differences appear to be correlated with the peptides' ability to form sheet-like assemblies. In particular, substantial conformational heterogeneity appears to be required for anisotropic growth of sheet-like materials, likely by reducing the peptide assembly kinetics. To test this hypothesis, we increased the pH to neutralize the lysine residues and promote peptide aggregation, and the resulting faster assembly rate hindered the growth of the sheet morphology as predicted. In addition, we designed and investigated the assembly morphologies of a series of diblock peptides with various lengths of polyglycine inserts, L5GxK10, x = 1, 2, 3, 4. The results further supported the importance of peptide conformational flexibility and pH in modulation of the peptide supramolecular assembly morphology. PMID- 26369068 TI - Fabrication of a Schottky Device Using CuSe Nanoparticles: Colloidal versus Microwave Digestive Synthesis. AB - Herein we report on a nearly ideal Schottky diode device fabricated from Cu(2 x)Se nanoparticles synthesized using the microwave digestive method. The thermionic theory using data extracted from the experimental I-V curve resulted in the ideality factor of 4.35 and the barrier height of 0.895 eV whilst the Cheung's method resulted in the ideality factor, barrier height and series resistance of 1.04, 0.00259 eV and 0.870 Omega respectively. The Cheung's method is thought to be the most accurate as it takes into account the series resistance. The obtained values therefore are indicative of good diode behaviour of the device and this is a highly sought after goal in all electronic materials development. PMID- 26369069 TI - Effect of Thermal Treatment on the Formation, Textural and Electrical Conductivity Properties of Nanocrystalline Tb4O7. AB - Nanocrystalline Tb4O7 was fabricated by the calcination of its precursor, which was prepared by the precipitation method using NaOH as a precipitant. The phase changes accompanying the thermal treatment of the terbium parent were monitored using X-ray diffractometry (XRD) and thermogravimetry (TGA). The Calcination was performed over the temperature range of 300-700 degrees C. The texture of the produced nanocrystalline Tb4O7 samples was investigated using field-emission scanning electron microscopy (FE-SEM) and nitrogen adsorption measurements at 196 degrees C. Transmission electron microscopy (TEM) was used to determine the crystallite size of the obtained Tb4O7. The obtained results reveal that Tb4O7 with crystallites that measured 6-12 nm was formed at 400 degrees C. The crystallite size increased to 15-29 nm for the sample calcined at 700 degrees C. The electrical conductance properties of the different calcined samples were investigated over the temperature range of 150-500 degrees C. The electrical conductivity was observed to increase with the calcination temperature. PMID- 26369070 TI - Characterization and Gas Sensitivity of Polyaniline/Coral-Like SnO2 Hybrid Material Prepared by In Situ Polymerization. AB - A PANI/coral-like mesoporous SnO2 hybrid material was fabricated using in situ polymerization method at 0-5 degrees C. The coral-like mesoporous SnO2 was synthesized by controlling the hydrolysis of SnCl4 and subsequent removal of the templates by calcination in air. The obtained PANI/coral-like mesoporous SnO2 hybrid material was characterized by FT-IR, XRD, TEM and SEM. The XRD pattern suggested that PANI did not modify the crystal structure of SnO2, but SnO2 affect the crystallization of PANI to some extents. The SEM and TEM pattern suggested that coral-like mesoporous SnO2 was enwrapped by PANI. The gas-sensing property of PANI/coral-like SnO2 hybrid material was also studied to NH3, trimethylamine (TMA), and SO2 at room temperature. It was found that the sensor based on PANI/coral-like SnO2 hybrid material had higher response and faster response/recovery to NH3, TMA and SO2 than that based on PANI. The sensing mechanism of the hybrid material was also investigated. PMID- 26369071 TI - A Way of Tailoring Magnetic Anisotropy of Co Nanowire Arrays: Magnetic Field Annealing. AB - Hexagonal close-packed Co nanowire arrays in anodic aluminum oxide template with the diameter of 50 nm have been fabricated using an ac electrodeposition method. The effect of magnetic field annealing on the thermal stability and magnetic properties of these nanwire arrays was studied. XRD measurements indicate the increase of diffraction intensity with the increase of heat-treatment temperature without magnetic field. Furthermore, the intensity of diffraction peak decreases rapidly if the sample undergoes the magnetic field annealing. Influence of different annealing process on the magnetic properties of Co nanowire arrays has also been studied. It is found that the magnetocrystalline anisotropy of hcp Co becomes weaker after magnetic field annealing, which lead to increase of the total anisotropy of Co nanowire arrays. PMID- 26369072 TI - Nanobiocomposite from Collagen Waste Using Iron Oxide Nanoparticles and Its Conversion Into Magnetic Nanocarbon. AB - Collagenous wastes discarded from leather industry were stabilized using superparamagnetic iron oxide nanoparticles and further converted into a magnetic nanocarbon. Stabilization of collagen using iron oxide nanoparticles treatment (25% offer) was confirmed through differential scanning calorimetric analysis and further evidenced through scanning electron microscopic analysis. A simple high temperature treatment of the collagen-iron oxide nanoparticle composite at 850 degrees C for 2 h under Ar atmosphere yielded a bi-functional, magnetic and conducting, nanocarbon. The X-ray diffraction and Raman spectroscopic analysis reveal the partial graphitation and X-ray photoelectron spectroscopic results show the presence of trace-iron containing carbon, naturally doped with nitrogen and oxygen. Transmission electron microscopic analysis show the presence of larger iron oxide nanocrystals embedded in graphitic carbon layers while superconducting quantum interference device based analysis reveals a perfect ferrimagnetic property with saturation magnetization. Thus, we have stabilized the collagen waste fibers using iron oxide nanoparticles and converted them into a bi-functional nanocarbon, which has potential for various applications including energy, leather making and environmental remediation. PMID- 26369073 TI - Effects of Different Carbon Matrix on the Pt0.55Co0.45 Catalysts Using for the Cathode of Proton Exchange Membrane Fuel Cell. AB - 20 wt% Pt0.55Co0.45/C catalysts were prepared using a chemical reduction method, with Vulcan XC-72 conducting furnace black and double-walled carbon nanotubes (DWCNTs) as the carbon supports, respectively. The catalysts were compared with commercial BASF 20 wt% Pt/C (using Vulcan XC-72 carbon as support). The materials were characterized by X-ray diffraction and transmission electron microscopy (TEM). The electrochemical performance of the Pt/C and Pt0.55Co0.45/C catalysts was evaluated by cyclic voltammetry and steady-state measurements. Electrochemical measurements indicated that the Pt0.55Co0.45 nanocatalysts exhibited improved activity in the oxygen reduction reaction (ORR) on DWCNTs compared to those on Vulcan XC-72 carbon. It is suggested that DWCNTs will provide better catalysis support than Vulcan XC-72 carbon. PMID- 26369074 TI - Low Temperature Synthesis of Rutile TiO2 Nanocrystals and Their Photovoltaic and Photocatalytic Properties. AB - We report a novel method of synthesizing rutile TiO2 nanocrystals at low temperature (200 degrees C) via a butanol rinsing process followed by heat treatment in an O2 atmosphere. The rutile nanocrystals show uniform size distribution of approximately 20 nm and good crystallinity confirmed by X-ray diffraction and transmission electron microscopy. A mechanism for the low temperature synthesis of rutile nanocrystals is rationalized in terms of an explosive thermal decomposition reaction of butoxy groups on TiO2 powders with O2 gas. Characterizations of the photovoltaic and photocatalytic properties of rutile nanocrystals exhibited higher photoactivity than large-sized conventional rutile powder, which demonstrates that this novel synthesis technology could expand applications of rutile powders to various photoactive devices beyond solar cells and photocatalysts. PMID- 26369075 TI - Controlled Patterning of Vertical Silicon Structures Using Polymer Lithography and Wet Chemical Etching. AB - In order to improve their performance for various applications, a facile method for the wafer-scale fabrication of micro/nano-patterned vertical silicon (Si) structures such as silicon nanowires (SiNWs), silicon nanorods (SiNRs), and porous silicon (p-Si) was developed. The method is based on the combination of lithography techniques (photolithography, thermal nano-imprint lithography, nanosphere lithography) and wet chemical etching (electro-chemical etching, metal assisted chemical etching) processes. Micro-patterned p-Si with various pore diameters from 30 nm to 1.2 um were fabricated via electro-chemical etching. Micro/nano-patterned Si microstructures, nanorods, and nanowires were also successfully fabricated by changing the thickness of the metal layer of 5 nm or 20 nm in the metal-assisted chemical etching process. This study also investigated the effect of the etching time and patterning on the etched SiNWs length. This method provides advantages of simplicity, speed, large-scale production, easy size and shape manipulation, and low cost. PMID- 26369076 TI - Effects of Processing Temperatures of Nickel Plating on Capacitance Density of Alumina Film Capacitor. AB - We observed the effects of nickel plating temperatures for controlling the surface morphologies of the deposited nickel layers on the alumina nano-pores. The alumina nano-channels were filled with nickel at various processing temperatures of 60-90 degrees C. The electrical properties of the alumina film capacitors were changed with processing temperatures. The electroless nickel plating (ENP) at 60 degrees C improved the nickel penetration into the alumina nano-channels due to the reduced reaction rate. Nickel layers are uniformly formed on the high aspect ratio alumina pores. Due to the uniform nickel electrode, the capacitance density of the alumina film capacitors is improved by the low leakage current, dissipation factor and equivalent series resistance. Alumina film capacitors made by ENP at 60 degrees C had a high capacitance density of 160 nF/cm2. PMID- 26369077 TI - Catalyst-Free Synthesis of ZnO Nanowires on Oxidized Silicon Substrate for Gas Sensing Applications. AB - In the present work, we report the synthesis of nanostructured ZnO by oxidation of zinc film without using a seed or catalyst layer. The zinc films were deposited on oxidized Si substrates by RF magnetron sputtering process. These were oxidized in dry and wet air/oxygen ambient. The optimized process yielded long nanowires of ZnO having diameter of around 60-70 nm and spread uniformly over the surface. The effect of oxidation temperature, time, Zn film thickness and the ambient has strong influence on the morphology of resulting nanostruxctured ZnO film. The films were characterized by scanning electron microscopy for morphological studies and X-ray diffraction (XRD) analysis to study the phase of the nanostructured ZnO. Room temperature photoluminescence (PL) measurements of the nanowires show UV and green emission. A sensor was designed and fabricated using nanostructured ZnO film, incorporating inter digital-electrode (IDE) for the measurement of resistance of the sensing layer. The gas sensing properties were investigated from the measurement of change in resistance when exposed to vapours of different volatile organic compound (VOC) such as acetone, ethanol, methanol and 2-propanol. The results suggest that ZnO nanowires fabricated by this method have potential application in gas sensors. PMID- 26369078 TI - Microwave Combustion Synthesis and Characterization Studies of Magnetic Zn(1 x)Cd(x)Fe2O4 (0 <= x <= 0.5) Nanoparticles. AB - Nano-sized pure and Cd-doped ZnFe2O4 (Zn(1-x)Cd(x)Fe2O4 with x = 0.0-0.5) samples were synthesized by a simple microwave combustion method. The X-ray diffraction (XRD) analysis confirmed the single phase cubic spinel structure. The average crystallite size was found in the range of 17.47-41.21 nm. The lattice parameter is found to increase with increase in the concentration of Cd. Pure ZnFe2O4 and all compositions of the Zn-Cd ferrites showed similar particle-like morphologies, which is confirmed by high resolution scanning electron microscopy (HR-SEM). Energy dispersive X-ray (EDX) analysis shows that the theoretical and observed percentage of the elements; Zn2+, Cd2+ and Fe3+ are in the desired stoichiometric proportion. The UV-Visible diffuse reflectance spectrum (DRS) shows the band gap value increases with increasing Cd content. All the samples showed the characteristic near-band-edge emission at around 428 nm, which is observed by photoluminescence (PL) spectra. The magnetic properties were measured by using vibrating sample magnetometer (VSM) and it was found that the saturation magnetization is increased with increase the concentration of Cd content. The results revealed that for lower Cd concentration (x = 0.0-0.2) the samples shows a superparamagnetic behavior, whereas for higher concentration (x = 0.3-0.5), it becomes ferromagnetic. PMID- 26369079 TI - DC-Bias-Superposition Characteristics of Ni0.4Zn0.2Mn0.4Fe2O4 Nanopowders Synthesized by Auto-Combustion. AB - Ni0.4Zn0.2Mn0.4Fe2O4 nanopowders were prepared by auto-combustion method. The as synthesized powders were characterized using X-ray diffraction (XRD) and thermo gravimetric-differential thermal analysis (TG-DTA), and the powders were densified at different temperatures 400 degrees C, 500 degrees C, 600 degrees C and 700 degrees C/4 hrs using conventional sintering method. The sintered samples were characterized by XRD and transmission electron microscope (TEM). The bulk densities of the samples were increased with an increase of sintering temperature. The grain sizes of all the samples vary in between 18 nm to 30 nm. The hysteresis loops show high saturation magnetization and low coercivity, indicates that it is a soft material. The incremental permeability (permeability with magnetic field superposition) was influenced by both DeltaM and H(c). A sample with higher initial permeability and favoured the attainment of a higher incremental permeability. The Q-factor was mainly determined by the sintered density and microstructure. To summarize, a uniform and dense microstructure with relatively small average grain size is favourable for obtaining better dc-bias superposition characteristics, including permeability and Q-factor. PMID- 26369080 TI - Synthesis of alpha-Fe2O3 Sphere/Rod-Like Nanostructure via Simple Surfactant-Free Precipitation Route: Optical Properties and Formation Mechanism. AB - Sphere/rod-like alpha-Fe2O3 nanostructure were successfully synthesized by simple surfactant-free precipitation route. The as-prepared samples were characterized by X-ray powder diffraction (XRD) to determine the phase purity and the crystal structure. The lattice parameter and crystallite size of the samples have been calculated from the Rietveld analysis. The crystallite size has been compared by Scherrer's formula and Rietveld method and both method showed increase of the grain size with the increase of the calcined temperature. The crystallite size was in the range of 5-30 nm. The high resolution scanning electron microscopy (HR SEM) analysis of the samples shows that the morphology of the nanostructures changed from nanospheres into nanorods and it was confirmed by high resolution transmission electron microscopy (HR-TEM). Energy dispersive X-ray (EDX) analysis reveals the presence of O and Fe elements only. The optical properties of the as prepared nanostructures were determined by photoluminescence (PL) spectra. The band gap energy was investigated by UV-Visible diffuse reflectance spectra (DRS) and calculated by means of the Kubelka-Munk method. The band gap values are decreased from 2.26 eV to 2.17 eV as the temperature increased from 300 degrees C to 400 degrees C with increasing the crystallite size. A Vibrating Sample Magnetometer (VSM) was used to study the magnetic properties of iron oxide (alpha Fe2O3) nanostructures. Magnetic hysteresis (M-H) loops revealed that the as prepared alpha-Fe2O3 samples displayed ferromagnetic behavior. PMID- 26369081 TI - Enhanced Capacitance of TiO2 Single Crystals Through Chemically Deposited Graphene Films. AB - Single-crystals of titanium oxide (TiO2) were wrapped in a graphene (G) film by chemical deposition. The morphology, composition and structure of the resulting composite were subsequently characterized by SEM, TEM, XRD and FT-IR analysis. The electrochemical properties of the composites were studied by cyclic voltammetry, which showed that the introduction of graphene enhances the electrode conductivity, thereby improving the supercapacitive behavior of TiO2. Galvanostatic charge-discharge tests demonstrated that a supercapacitor device fabricated from TiO2 crystals wrapped in graphene (G-TiO2) exhibits a good cycle life, with 94% stability even after 1000 cycles. PMID- 26369082 TI - A Novel Process for the Preparation of Ni0.5Zn0.5Fe2O4 Nanoparticles and Their Removal Behaviors of RR-2BF. AB - A novel solution combustion and calcination process has been reported for the preparation of magnetic Ni0.5Zn0.5Fe2O4 nanoparticles. The morphology, chemical composition, microstructure and magnetic properties of as-prepared Ni0.5Zn0.5Fe2O4 nanoparticles were investigated by XRD, TEM, SAED and VSM. The magnetic Ni0.5Zn0.5Fe2O4 nanoparticles were characterized with average grain size of about 18 nm and specific magnetization of 90.4 Am2/kg. The nanoparticles were employed to remove reactive red 2BF (RR-2BF) from aqueous solutions; and the adsorption kinetics and the adsorption isotherms were investigated by UV spectroscopy at room temperature; the regression equation was found in good agreement with the pseudo-second-order kinetic model in a range of initial concentration of 50-200 mg/L. Compared with Freundlich and Temkin models, Langmuir model fits the adsorption isotherm of RR-2BF onto the magnetic Ni0.5Zn0.5Fe2O4 nanoparticles better, which suggested that the adsorption of RR 2BF onto the magnetic Ni0.5Zn0.5Fe2O4 nanoparticles was monolayer, and the adsorption energy was constant. PMID- 26369083 TI - A Novel Synthesis and Characterization Studies of Magnetic Co3O4 Nanoparticles. AB - Cobalt oxide (Co3O4) nanoparticles were synthesized by microwave combustion method (MCM) using urea as the fuel. For the purpose of comparison, they are also prepared by conventional combustion method (CCM). The prepared samples were examined by using X-ray diffraction (XRD), high resolution scanning electron microscopy (HR-SEM), high resolution transmission electron microscopy (HR-TEM), UV-Visible diffuse reflectance spectroscopy (DRS), photoluminescence (PL) spectroscopy and vibrating sample magnetometer (VSM). XRD analysis indicated that the as-prepared samples have well-crystalline cubic phase. HR-TEM images showed that Co3O4 nanoparticles have sphere-like structure with an average particle size in the range of 20-25 nm (MCM) and 45-50 nm (CCM). Optical properties of Co3O4 nanoparticles revealed the presence of two band gap (1.89 and 2.54 eV (MCM), 1.68 and 2.38 eV (CCM)) values, which in turn confirmed the semi-conducting properties. VSM measurements revealed a small hysteresis loop at room temperature thus indicating a weak ferromagnetism. PMID- 26369084 TI - Size-Dependent Multi- to Single Domain Transition of UV Laser-Driven Ferromagnetic Co Nanoparticles Under External Magnetic Field. AB - The magnetic domain of cobalt (Co) nanoparticles (NPs) was studied as a function of particle size. Various single crystalline and uniform Co NPs were prepared using a novel UV laser irradiation technique on ultra thin Co films under an external applied magnetic field. Structural and magnetic characteristics were analyzed with transmission electron microscopy and superconducting quantum interference devices. The experimental observations indicate that during Co NP growth, externally applied magnetic fields and size-dependent NP surface effects strongly facilitate multi-to-single domain transition at a critical diameter of about 10 nm, an extremely small NP size that is suitable for higher density storage applications. PMID- 26369085 TI - In Situ Fabrication and Characterization of Graphene Electronic Device Based on Dual Beam System. AB - The graphene, as a one atomic-layer material, is very sensitive to the environment and easy to be polluted. Here, we propose an in situ fabrication and characterization method for graphene electronic devices using the Dual Beam system. Instead of the conventional photo/e-beam lithography, plasma etching and lift-off techniques, the focused ion beam (FIB) is employed to pattern the graphene and the e-beam induced deposition of platinum (Pt) is adopted to fabricate the electrodes. Using the nano-probes in the specimen chamber, we obtained the typical electronic bipolar behavior of graphene in situ both with the Pt/graphene contact and the nano-probes/graphene direct contact. In the whole process of the fabrication and characterization, the graphene sample is kept in high vacuum condition all the time. PMID- 26369086 TI - Preparation and Application of Modified Magnetic Particles to Remove Phosphate in Aqueous Media. AB - In this work, magnetic particles were firstly protected by oleic acid, and then polymers, the polymers was prepared with allyl-thiourea as the functional monomer, ethyleneglycol dimethacrylate as the cross-linking agent, 2,2 azobisisobutyronitrile as the initiator, and acetonitrile as the solvent. The magnetic polymers were analyzed by FT-IR, X-ray diffraction, and a vibrating sample magnetometer to obtain the morphological and magnetic properties. The adsorption of phosphate on the magnetic polymers was investigated, including pH effect, initial concentration, and temperature. The results proved that the adsorbent was paramagnetic and successfully loaded with the poly-thiourea group. The data was well fitted to the Langmuir adsorption isotherm, and the maximum adsorption capacity was 55.20 mg-P g(-1). Furthermore, desorption of phosphate from the adsorbent could be achieved efficiently by 0.5 mol L(-1) NaOH, reusability was studied by repeating adsorption-desorption cycles five times. PMID- 26369087 TI - Study of Well Width in InGaN/GaN Multiple Quantum Well Light-Emitting Diodes. AB - The optical and structural properties of InGaN/GaN multi-quantum wells (MQWs) grown on sapphire by metalorganic chemical vapor deposition (MOCVD) have been investigated by optical measure- ments of photoluminescence (PL), and structural analysis methods of high-resolution X-ray diffrac- tion (HRXRD) and high resolution transmission electron microscopy (HRTEM). Two typical samples are studied, both consisting of five periods of GaN barrier width of 11.8 nm with different InGaN well width of 2.95 nm and 1.7 nm. These results indicate that the crystal and optical properties of InGaN/GaN MQWs are improved with the narrower of the InGaN well width. The indium compositions, GaN barrier width and InGaN well width can be achieved by HRXRD simulation software, and the result is consistent with actual growth conditions of InGaN/GaN MQWs. PMID- 26369088 TI - Superparamagnetic Fe3O4/Poly(N-isopropyl acrylamide) Nanocomposites Synthesized in Inverse Miniemulsions: Magnetic and Particle Properties. AB - In the present study, superparamagnetic Fe3O4/poly(N-isopropyl acrylamide) nanocomposites were synthesized by one-step inverse miniemulsion copolymerization of N-isopropyl acrylamide and N,N'-methylene diacrylamide. The loading of Fe3O4 nanoparticles in the nanocomposites was 27 wt%, and the saturation moment of the nanocomposites was 12.4 emu x g(-1). Fe3O4 nanoparticles were prepared through a coprecipitation method. The amount of stabilizer (poly(acrylic acid)) significantly influenced the size and size distribution of the Fe3O4 nanoparticles, and, therefore, their magnetic properties. Superparamagnetism of the Fe3O4 nanoparticles was preserved in the nanocomposites. The effects of synthetic parameters on the particle properties, namely surfactant loading, concentration of ferrofluid, type of lipophobe and initiator, and amount of cross linker were investigated. Nanocomposites of Fe3O4/poly(N-isopropyl acrylamide) displayed a guava-like morphology, which they could retain after being redispersed in polar solvents. PMID- 26369089 TI - Attempt of Deposition of Ag-Doped Amorphous Carbon Film by Ag-Cathode DC Plasma with CH4 Flow. AB - A simple DC plasma apparatus having large Ag cathode with CH4 flow was used for the attempt to prepare Ag-doped amorphous carbon film. As the gaseous source, CH4 and the additive (N2 or Ar) were used for the plasma process. When N2 was the additive, the substrate surfaces after the plasma process were electrical conductor although high electrical resistance. The growth rate of the deposits decreased with increasing the amount of N2, and the deposits contained nitrogen. Although the small amount of silver was detected by XPS, the peak for Ag may not be in the carbon deposit but be in interlayer formed at Ar etching process. When Ar was the additive, the substrate surfaces after the plasma process were also electrical conductor although high electrical resistance. The growth rate of the deposits was almost independent of the amount of Ar, and the deposits contained no argon. The small XPS peaks for Ag may not be in the carbon deposit but be in interlayer formed at Ar etching process. Both the prepared samples had high antibiotic property. The method of this study could be used for the surface reforming with amorphous carbon coating having electrical conductivity and antibiotic property. PMID- 26369090 TI - Zn(1-x)Cu(x)O (0.02 <= x <= 0.1) Nanomaterials Prepared by Ball Milling, Citrate Sol Gel, and Molten Salt Flux Methods. AB - The Cu doped ZnO, (Zn(1-x)Cu(x))O (x = 0.02, 0.04, 0.06, 0.08, and 0.1) nanomaterials were prepared by ball milling technique (BMT), citrate sol gel (CSG), and molten salt flux (MSF) methods. The various as-prepared (Zn(1 x)Cu(x))O materials were analyzed by powder X-ray diffraction (pXRD), FT-IR, and SEM-EDX measurements in order to check the phase formation, purity, surface morphology and elements present in the annealed materials. Due to the preparation methods as well as doping of 'x' slight variations in cell parameters are seen. The average crystalline size of CSG method shows smaller size (25-35 nm) than BMT and MSF approaches. The materials obtained by MSF technique reveal the average crystalline size in the range of 32-72 nm whereas the BMT materials exhibit 36-50 nm for the composition, 0.02 <= x <= 0.1. The presence of functional groups and the chemical bonding in (Zn(1-x)Cu(x))O system is confirmed through FT-IR measurements. It is evident from the FT-IR data that bands seen at 400-500 cm(-1) are characteristics of M-O (M = metal ion) bonding in the studied materials. The micro images observed by SEM exhibiting polycrystalline character as compared with the crystallite size obtained from XRD. Among the three approaches employed in the present investigations, in terms of average particle size the CSG method may be concluded as an efficient method for the preparation of Zn(1-x)Cu(x)O nanomaterials. PMID- 26369091 TI - The Effects of Diamond-Like Carbon Films on Fretting Wear Behavior of Orthodontic Archwire-Bracket Contacts. AB - This study aims to assess the effects of diamond-like carbon (DLC) films on fretting wear behavior of orthodontic archwire-bracket contacts. 'Mirror confinement-type electron cyclotron resonance (MCECR) plasma sputtering' was utilized to deposit carbon films on stainless steel archwires and brackets. Nanostructure of carbon films such as the bonding structure, cross-sectional thickness and surface roughness were studied. The fretting wear behavior of various archwire-bracket contacts were investigated by using a self-developed tester in ambient air and artificial saliva. The results indicated that DLC coated wires showed significantly low friction coefficient than the uncoated wires independently of the applied environments. Nevertheless, the DLC-coated and uncoated brackets showed no significant differences in the friction coefficient. Microscopic analysis showed that low wear took place for the DLC-coated surfaces. It is proposed that the application of DLC coating on archwires can decrease the orthodontic fretting wear and coefficient of friction. Unfortunately it does not affect the frictional properties for brackets at present. PMID- 26369092 TI - Water-Soluble Fluorescent CdTe/ZnSe Core/Shell Quantum Dot: Aqueous Phase Synthesis and Cytotoxicity Assays. AB - In this manuscript, we demonstrate a novel, facile and environmentally friendly method to directly obtain CdTe/ZnSe core/shell QDs in the aqueous phase based on the method of epitaxial growth of ZnSe shells on CdTe cores. The ZnSe shell and the capping reagent glutathione of the CdTe/ZnSe core/shell QDs greatly increased the biocompatibility and stability of the original CdTe cores. The optical property of the as-prepared CZ QDs could be controlled by precisely adjusting the size of CdTe cores, which showed broad emission spectra from 530 to 688 nm. The crystalline structure of the CZ QDs was extensively characterized by XRD, TEM and HRTEM, etc. Furthermore, since there were several functional groups on glutathione molecules, the QDs could be potentially used for connecting other functional small molecules, biomolecules or nanoparticles. Such QDs have bright future perspectives in the development biological and nanomedical fields. PMID- 26369093 TI - Preparation and Characterizations of Rosin Based Thin Films and Fibers. AB - In this study, we report the preparation and comparison of the rosin based thin films and electrospun fibers in terms of their formation and characterizations. Rosin in the form of thin films and fibers can be obtained via wet casting method and electrospinning process, respectively. Systematic experiments were performed to study the morphology, structure and thermal properties of the rosin thin films and electrospun fibers. Finally, in order to understand the accurate mass values of rosin in the different morphologies, we performed matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) spectroscopy. The rosin thin film prepared via wet casting method exhibited very smooth surfaces whereas the electrospun fibers were continuous without any beads over long distances. The MALDI-TOF data revealed that the most intense peak in the molecular weight of rosin components is about 302 for the rosin powder, thin film and fibers. On the other hand, some of the higher molecular component can also be observed for electrospun rosin fibers owing to the structural morphology. The present study demonstrated that the full structural characterization of the molecular species present in these different forms of rosin. PMID- 26369094 TI - Laser Field Effects on Optical Properties in the Zinc-Blende GaN/AlGaN Quantum Well. AB - Based on the effective mass approximation, the laser field effects on exciton states and optical properties in the zinc-blende (ZB) GaN/AlGaN quantum well (QW) are investigated by means of a variational method. Numerical results show that the ground-state exciton binding energy, the emission energy, the oscillator strength, and the linear optical susceptibility are highly dependent on the well width and laser field amplitude in the ZB GaN QW. The laser field decreases the exciton binding energy and the oscillator strength; however, it also increases the emission energy in the QW for any well width. In particular, our results also show that the laser field has remarkable effects on the exciton states and optical properties in the ZB GaN/AlGaN QW with the small well width case. PMID- 26369095 TI - The Effect of Synthesis Conditions on Mesoporous Structure and the Photocatalytic Activity of TiO2 Nanoparticles. AB - Mesoporous TiO2 nanoparticles have been synthesized by sol-gel method in different preparation conditions to investigate the effect of triblock copolymer, acetic acid and water on mesoporous structure and the photocatalytic activity. The synthesized photocatalysts were characterized by means of X-ray powder diffraction, Nitrogen adsorption/desorption studies, High resolution transmission electron microscopy, Scanning electron microscopy, Diffuse reflectance UV-Vis spectroscopy, Fourier transform infrared spectroscopy, Raman spectroscopy and thermogravimetric analysis. Among the various synthesized materials, mesoporous TiO2 synthesized using triblock copolymer as a structure directing template in acetic acid medium with high water ratio calcined at 400 degrees C was found to have the highest photocatalytic activity due to the enhanced band gap energy, high specific surface area and high average pore size. The large mesopores provide more pathways for the reactants to enter and products to escape and enhances the adsorption of methylene blue. The photocatalytic activity decreases with increase of solution pH. The rate of *OH formation is high at lower pH, which enhances the photocatalytic activity was revealed by photoluminescence technique. In addition, the adsorbed hydroxyl groups on the surface of mesoporous TiO2 particles can interact with photogenerated holes to produce more *OH radicals, which enhances charge transfer efficiency and enhances the rate of *OH formation. PMID- 26369096 TI - Synthesis and Characterization of Hollow TiO2 Particles Coated with Polyimide Brushes by Click Chemistry. AB - In order to improve the compatibility between nanoparticles and polymer matrix, a feasible processing way for grafting polyimides (PI) on the surface of hollow TiO2 particles was developed. Hollow TiO2 spheres were prepared by using polystyrene-methyl acrylic acid latex as a template starting from tetrabutyl titanate. Surface graft of azide-decorated hollow TiO2 spheres with well-defined alkyne-terminated PI were achieved by "click" chemistry in three steps: (1) choloromethylation and azidization of hollow TiO2, (2) preparation of alkyne terminated PI by polycondensation, (3) click coupling between the azidized hollow TiO2 and the alkyne-terminated PI under the catalysis of CuSO4/sodium ascorbate. Fourier transform infrared (FTIR) and Nuclear Magnetic Resonance (1HNMR) spectra were used to illustrate quantitative transformation of the PI brushes on hollow TiO2 particles into the desired functional group. The morphology of hollow TiO2 PI composite particles was characterized by transmission electron microscopy (TEM) which showed the irregular hollow structure. The results indicate that the grafting of polymer chains with thermostability and flame retardance on the surface of hollow TiO2 sphere is successful. PMID- 26369097 TI - Nanocomposite of Au Nanoparticles/Helical Carbon Nanofibers and Application in Hydrogen Peroxide Biosensor. AB - A combined sol-gel/hydrogen reduction method has been developed for the mass production of helical carbon nanofibers (HCNFs) by the pyrolysis of acetylene at 425 degrees C in the presence of NiO nanoparticles. The synthesized HCNFs were characterized with scanning electron microscopy (SEM), X-ray diffraction (XRD) and high resolution transmission electron microscopy (HRTEM). The helical structured carbon nanofibers have a large specific surface area and excellent biocompatibility. A novel enzymatic hydrogen peroxide sensor was then successfully fabricated based on the nanocomposites containing HCNFs and gold nanoparticles (AuNPs). The results indicated that the Au/HCNFs nanocomposites exhibited excellent electrocatalytic activity to the reduction of H2O2, offering a wide linear range from 1.0 MUM to 3157 MUM with a detection limit as low as 0.46 MUM. The apparent Michaelis-Menten constant of the biosensor was 0.61 mM. The as-fabricated biosensor showed a rapid and sensitive amperometric response to hydrogen peroxide with acceptable preparation reproducibility and excellent stability. Because of their low cost and high stability, these novel HCNFs represent seem to be a kind of promising biomaterial and may find wide new applications in scopes such as biocatalysis, immunoassay, environmental monitoring and so on. PMID- 26369098 TI - The Influence of Phase Separation on Bioactivity of Spray Pyrolyzed Bioactive Glass. AB - In this study, bioactive glass (BG) particles were synthesized directly using spray pyrolysis (SP). Since the bioactivity of glass particles is well correlated with their chemical composition, how to obtain homogenous bioactive glass becomes an important issue. For SP, the main reason for chemical inhomogeneity was considered to be caused by the difference in the precipitation speed of each precursor. So, two Si-containing precursors of BG, namely tetraethyl orthosilicate (TEOS) and silicon acetate (SiA), have been applied to prepare BG particles. The bioglasses were characterized by X-ray diffraction, scanning electron microscopy, transmission electron microscopy and energy dispersive spectroscopy to examine their phase composition, and surface structures, inner morphologies and chemical compositions. It was observed that, under the calcination temperature of 700 degrees C, TEOS-derived powder contained Si-rich nanoparticles and Si-deficit submicron particles as inhomogeneity, whereas the SiA-derived powder was homogenous. The reason of inhomogeneity is that TEOS dissolves in "volatile" ethanol more readily than in water via the SP mechanism of "gas-to-particle-conversion" to form Si-rich nanoparticles. The presence of Si rich nanoparticles causes Si-deficit "wollastonite submicron particles" to form, which impairs the bioactivity. Finally, BG particle formation mechanisms from different precursors have been proposed. PMID- 26369099 TI - Simultaneous Determination of Adenine and Guanine Using Cadmium Selenide Quantum Dots-Graphene Oxide Nanocomposite Modified Electrode. AB - A novel electrochemical sensor was fabricated by immobilizing Cadmium Selenide Quantum Dots (CdSe QDs)-Graphene Oxide (GO) nanocomposite on a paraffin wax impregnated graphite electrode (PIGE) and was used for the simultaneous determination of adenine and guanine. The CdSe QDs-GO nanocomposite was prepared by ultrasonication and was characterized with spectroscopic and microscopic techniques. The nanocomposite modified electrode was characterized by cyclic voltammetry (CV). The modified electrode showed excellent electrocatalytic activity towards the oxidative determination of adenine and guanine with a good peak separation of 0.31 V. This may be due to the high surface area and fast electron transfer kinetics of the nanocomposite. The modified electrode exhibited wide linear ranges from 0.167 MUM to 245 MUM for Guanine and 0.083 MUM to 291 MUM for Adenine with detection limits of 0.055 MUM Guanine and 0.028 MUM of Adenine (S/N = 3) respectively. Further, the modified electrode was used for the quantitative determination of adenine and guanine in herring sperm DNA with satisfactory results. The modified electrode showed acceptable selectivity, reproducibility and stability under optimal conditions. PMID- 26369100 TI - Fabrication and Characterization of Poly(lactic acid)/Poly(epsilon-caprolactone) Blend Electrospun Fibers Loaded with Amoxicillin for Tunable Delivering. AB - Blends of poly(lactic acid) (PLA) and poly(epsilon-caprolactone) (PCL), loaded with different amounts of Amoxicillin antibiotic (AMOX) were electrospun to investigate their release properties and obtain a controlled and tuneable release. The processing parameters for electrospinning were set up and reliable membranes were obtained. Morphology and thermal behaviour were found dependent on the component ratio as well as on the incorporated drug amount. A very different release kinetics of the two pristine polymers, very rapid for PCL and very slow for PLA, reflected in intermediate release time. However comparing the release amount with that predicted by the mixture rule a preferential incorporation of AMOX into PLA can be inferred. PMID- 26369101 TI - A Novel Seed-Assisted Route for Fabricating Potassium Titanoniobate Photocatalytic Nanomaterials. AB - A novel, facile and mild preparation route was proposed to synthesize well crystallined potassium titanoniobate (KTiNbO5) powders with pure phase and mono dispersed particle morphology. The preparation process mainly included a hydrothermal reaction under temperature of 200 degrees C, then following with a short time calcining at 500 degrees C. The utility of crystal seed during the hydrothermal process was essential and pivotal. Most importantly, only the crystal seed was prepared through a particular sol-gel process, was the desired KTiNbO5 particles successfully achieved. The unique effect of such crystal seed was discussed in detail. We demonstrated that particle quantity and morphology of the crystal seed was a key point for the successful preparation. The KTiNbO5 particles synthesized in this work exhibited thin and rectangular particle shape with the average size around one micron. Moreover, the photocatalytic behavior of such KTiNbO5 powders was investigated. It was proved that such KTiNbO5 powders had potential applications as photocatalytic materials. PMID- 26369102 TI - Spectroscopy and Calculations for f-f Transitions of Tb3+ Ions in KY3F10 Nanocrystal. AB - A modified Judd-Ofelt theory is used in this paper to treat the electric dipole transitions within the 4f8 configuration of Tb3+ by considering the main perturbing components. Through the energy-level calculation and the strandard tensorial analysis, the explicit distances between the 4f7 5d configuration and the 5D4 state and other lower 4f8 energy levels are determined. The rare-earth ion Tb3+ substituted at Y3+ sites in KY3F10 has the site symmetry of C4v. The standard Judd-Ofelt parameters A2(10), A2(30), A4(30), A4(50), A6(50), A4(54) and A6(54) are included in the calculation together with odd-lambda parameters A1(10), A3(30), A5(50) and A5(54). The fluorescence branching ratios originating from 5D4 are calculated. Compared with the experimental measurements, the modified model yields better results than the standard Judd-Ofelt theory. PMID- 26369103 TI - Chemoenzymatic Synthesis of Amphiphilic Core-Shell TMP-(PCL-b-PGMA2)3 Star-Block Copolymer. AB - A novel well-defined amphiphilic Core-Shell star-block copolymer was synthesized from trimethylolpropane, epsilon-caprolactone, and glycidyl methacrylate by a combination of enzymatic ring-opening polymerization and atom transfer radical polymerization. The structure and molecular weight of the macroinitiator and the star-block copolymer were confirmed by means of nuclear magnetic resonance and gel permeation chromatography. The effects of the glycidyl methacrylate sequence length on the hydrodynamic diameter and morphology of the polymer micelles were investigated by dynamic light scattering and transmission electron microscopy, respectively. PMID- 26369104 TI - Photocatalytic Degradation of Congored on Silica Supported Ag Impregnated TiO2. AB - Advanced oxidation process using nano sized silver impregnated titania-silica composite catalysts for the degradation of carcinogenic dye has been investigated. x% Silver/y% Titania/Silica. (x = 1%, 4%, 7% and 10%; and y = 10%, 15%, 20% and 25%), composite photocatalysts were synthesized by a three step process and characterized by using various physicochemical analytical techniques and evaluated for their photocatalytic activities towards decolourization/degradation of Congo red. The photodecolourisation and the photodegradation were monitored by using UV-Visible spectrophotometer and Total Organic Carbon analyzer respectively. The effects of various operating variables such as percentage loading of titania and silver on the decolourization/degradation of Congo red dye were studied, optimized and compared. Impregnation of silver increased the photocatalytic activity. 1% Silver/Titania/Silica composite catalyst showed better photocatalytic activity than titania-silica composite catalysts. However further increase of silver to 4%, 7% and 10% did not show any significant improvement in photocatalytic activity. Among the catalysts synthesized 1% silver/25% titania/silica composite catalyst was found to show the best decolourization and degradation of Congo red. PMID- 26369105 TI - Effect of Poly(ethylene glycol) Spacer on Peptide-Decorated Hepatocellular Carcinoma-Targeted Lipoplexes In Vitro. AB - Hepatocellular carcinoma (HCC) is a leading cause of cancer related deaths and is particularly prevalent in regions where Hepatitis B is highly endemic. Classical treatment options are largely limited to surgical measures and transcatheter chemoembolization. However biopanning of phage display libraries has identified very selective HCC-targeting peptides, which may be tethered to cationic liposomes for non-viral delivery of therapeutic DNA to affected cells thus providing a foundation for the development of new gene therapy treatment approaches. In this investigation, a cysteinylated HCC-tropic peptide has been linked directly to cationic liposomes, containing the cytofectin 3beta-[N-(N',N' dimethlaminopropylamino)-carbamoyl]-cholestero (Chol-T) and dioleolphosphatidyl ethanolamine, via a novel membrane-embedded maleimido cholesteryl derivative 3-[N (hydrazino-y-maleimidobutyryl)-carbamoyl] cholesterol (Chol-Mal), or with an intervening poly(ethylene glycol) spacer element. The effect that inclusion of the hydrophilic polymer has on targeted lipoplex-mediated gene delivery in the human HCC cell line HepG2 has been investigated. Results show that both systems bind DNA and transfect this cell line with equal efficiency, while transgene expression levels in human embryo kidney cells HEK293 were low and comparable to those achieved in competition assays in HepG2 cells and by lipoplexes decorated with scrambled peptides. Although inclusion of poly(ethylene glycol) in formulations should be considered for in vivo studies, we show here that it offers no advantage in this application in vitro. PMID- 26369106 TI - Spontaneous Growth of Ultra-Long SiO(x) Nanowires from SiC Thin Films by Thermal Annealing. AB - The use of a simple thermal treatment for growing ultra-long SiO(x) nanowires on silicon carbide (SiC) thin films is reported for the first time. SiC thin films with a thickness of 100 nm were prepared by sputtering at room temperature followed by annealing in an Ar/H2 gas atmosphere. The growth of SiO(x) nanowires started when the annealing temperature was at 1200 degrees C, and was rapidly and spontaneously grown at temperatures above 1250 degrees C. The diameters of as grown SiO(x) nanowires with lengths up to several hundred micrometers were determined to be -1 MUm. PMID- 26369107 TI - Synthesis of Highly Photocatalytic TiO2 Microflowers Based on Solvothermal Approach Using N,N-Dimethylformamide. AB - Crystallized anatase TiO2 microflowers with high surface area are synthesized by a simple template-free solvothermal method using N,N-dimethylformamide (DMF). Titanium sources undergo well-organized assembly in DMF to form flower-shaped TiO2 particles. After the calcination, the anatase frameworks are highly crystallized, and the surface area is increased up to 256 m2 x g(-1). The calcined TiO2 microflowers show superior photocatalytic performance over the commercially available TiO2 product (P25) in the degradation of methylene blue. PMID- 26369108 TI - Applications of Nanomaterials in Radiotherapy for Malignant Tumors. AB - Malignant tumors are tremendous heath problems facing by the medical world. In order to achieve the purpose of curing malignant tumor, numerous therapeutic strategies have been developed. Radiotherapy is one of the main therapeutic strategies for malignant tumors. Current imaging strategies cannot display exact infiltrating margins, radio-resistance generated by irradiated tissue, and intercurrent damage to healthy tissues during radiotherapy. Therefore, novel strategies to solve these problems are urgently needed. Nanomaterials have specific physical and biological properties that can help clinician to distinguish margins of infiltrating tumors as a novel contrast agent. Besides, nanoparticles can significantly enhance the effect of radiotherapy by generating reactive oxygen species (ROS) or influence cell cycle. In addition, nanomaterials can also help in diminishing the intercurrent damage caused by radiotherapy. So nanomaterials have very promising prospect in the radiotherapy of malignant tumors. This review mainly focuses on the applications of nanomaterials in radiotherapy for malignant tumors; especially it applies to lesion imaging and their radiosensitizing effects. PMID- 26369109 TI - Carbon Nanomaterials for Drug Delivery and Cancer Therapy. AB - Nanotechnology is one of the most exciting disciplines and it incorporates physics, chemistry, materials science, and biology. It can be applied to design cancer medicines with improved therapeutic indices. At the basic level, carbon nanotubes (CNTs) and graphene are sp2 carbon nanomaterials. Their unique physical and chemical properties make them interesting candidates of research in a wide range of areas including biological systems and different diseases. Recent research has been focused on exploring the potential of the CNTs as a carrier or vehicle for intracellular transport of drugs, proteins, and targeted genes in vitro and in vivo. Several research groups are actively involved to find out a functional CNT carrier capable of transporting targeted drug molecules in animal models with least toxicity. Current investigations are also focused on graphene, an allotrope of carbon, which appears to be a promising agent for successful delivery of biomolecules in various animal models. But potential clinical implementations of CNTs are still hampered by distinctive barriers such as poor bioavailability and intrinsic toxicity, which pose difficulties in tumor targeting and penetration as well as in improving therapeutic outcome. This article presents recent progresses in the design and evaluation of closely related CNTs for experimental cancer therapy and explores their implications in bringing nanomedicines into the clinics. PMID- 26369110 TI - Enhanced Cellular Uptake of Silica-Coated Magnetite Nanoparticles Compared with PEG-Coated Ones in Stem Cells. AB - Monodispersed magnetite (Fe3O4) nanoparticles (NPs) were prepared through the thermal decomposition method. The obtained NPs were surface modified with silica (SiO2) and polyethylene glycol (PEG), to enhance their stability in aqueous environment and their cellular uptake efficiency for biomedical applications. The NPs were characterized by X-ray diffraction (XRD), high-resolution transmission electron microscopy (HR-TEM), Fourier transform infrared (FT-IR) spectroscopy, and dynamic light scattering (DLS). The cytotoxicity of these NPs on bone marrow mesenchymal stem cells (BM-MSCs) was measured by MTT assay (cell viability test) at various concentrations (2, 5, 12.5, 25, and 50 ug/mL). The cells remained more than 90% viable at concentrations as high as 50 ug/mL. To compare the cellular uptake efficiency, these NPs were treated in BM-MSCs and the Fe concentration within the cells was measured by inductively coupled plasma-atomic emission spectrometry (ICP-AES) analysis. The uptake process displayed a time- and dose dependency. The uptake amount of SiO2-coated Fe3O4 (Fe3O4@SiO2) NPs was about 10 times higher than that of the PEG-coated ones (Fe3O4@PEG). PMID- 26369111 TI - The Role of Magnesium Ion Substituted Biphasic Calcium Phosphate Spherical Micro Scaffolds in Osteogenic Differentiation of Human Adipose Tissue-Derived Mesenchymal Stem Cells. AB - This study was investigated the role of magnesium (Mg2+) ion substituted biphasic calcium phosphate (Mg-BCP) spherical micro-scaffolds in osteogenic differentiation of human adipose tissue-derived mesenchymal stem cells (hAT MSCs). Mg-BCP micro-scaffolds with spherical morphology were successfully prepared using in situ co-precipitation and spray drying atomization process. The in vitro cell proliferation and differentiation of hAT-MSCs were determined up to day 14. After in vitro biological tests, Mg-BCP micro-scaffolds with hAT-MSCs showed more enhanced osteogenicity than pure hAT-MSCs as control group by unique biodegradation of TCP phase and influence of substituted Mg2+ ion in biphasic nanostructure. Therefore, these results suggest that Mg-BCP micro-scaffolds promote osteogenic differentiation of hAT-MSCs. PMID- 26369112 TI - Label-Free Detection of Ag+ Based on Gold Nanoparticles and Ag+-Specific DNA. AB - A sensitive label-free method was presented for the determination of silver ion (Ag+) in this paper. Cytosine-rich DNA (C-DNA) was used as Ag+ specific DNA. Without Ag+ in the solution, fluorescence of fluorescein (FAM) is quenched by C DNA stabilized gold nanoparticles (AuNPs) in high salt environment. When Ag+ is present in the solution, however, Ag+-mediated cytosine-Ag+-cytosine (C-Ag+-C) base pairs induced the C-DNA folding into a hairpin structure, which can not stabilize AuNPs in high salt environment, thus causing AuNPs aggregation. After centrifugation to remove the aggregated AuNPs, the quenching ability of the supernatant for FAM is decreased and the fluorescence intensity of solution increases with increasing the Ag+ concentration. Due to the highly specific interaction of the C-DNA towards Ag+ and the strong fluorescent quenching ability of AuNPs for FAM, the method has high selectivity and sensitivity for Ag+. Under the optimal conditions, the fluorescence intensity at 515 nm increased linearly with the concentration of Ag+ ranging from 15 nM to 700 nM, and the detection limit was determined as 6 nM based on 3 sigma/slope. This method is simple, sensitive, and may be applied to other detection systems by selecting the appropriate DNA sequences. PMID- 26369113 TI - Characterization and Insights Into the Nano Liposomal Magnetic Gene Vector Used for Cell Co-Transfection. AB - The development of magnetofection technology has brought a promising method for gene delivery. Here, we develop a novel liposomal magnetofection system, consisted of magnetic nanoparticle and liposome through molecular assembly, was applied to introduce double genes into porcin somatic cells with high co transfection efficiency. The performace of liposomal magnetic gene nanovectors has been evaluated by involving the micro morphology, diameters distribution, zeta potentials and the capacity of loading DNA molecules. The assembly way among magnetic gene nanovectors and DNA molecules was investigated by atomic force microscopy. Liposomal nano magnetic gene vectors complexes displayed nanoscale assembly and formed compact "fishing-net structure" after combining with plasmid DNA, which is favorable to enhance the loading capacity of DNA molecules. PMID- 26369114 TI - Fatigue Test of Cytochrome C Self-Assembled on a 11-MUA Layer Based on Electrochemical Analysis for Bioelectronic Device. AB - A cytochrome c/11-MUA heterolayer was fabricated to analyze its electrochemical characteristics in harsh conditions for a stable bioelectronic device. Since a cytochrome c/11-MUA heterolayer has been applied to construct the bioelectronics device such as non-volatile biomemory device, an understanding of electrochemical property of the heterolayer in harsh conditions such as variation of temperature and pH, and repetition of usage is necessary to manufacture a stable platform of bioelectronic device. Cytochrome c, a metalloprotein to have a heme group, was self-assembled on the Au surface via the chemical linker 11-mercaptoundecanoic acid (11-MUA). Immobilization of the heterolayer was confirmed by surface enhanced Raman spectroscopy (SERS) and scanning tunneling microscopy (STM). The fatigue test was done by investigating the redox properties based on cyclic voltammetry (CV) of the heterolayer. The retention time test and pH dependence, thermal test of the fabricated heterolayer were conducted by CV, which showed that the fabricated film retained redox properties for more than 33 days, and from pH 5.0 to pH 9.0, from 15 degrees C to 55 degrees C. Taken together, our results show that a cytochrome c/11-MUA heterolayer is very stable, which could be used as a platform of bioelectronic device. PMID- 26369115 TI - Silver Nanoparticles Synthesized Using Caesalpinia sappan Extract as Potential Novel Nanoantibiotics Against Methicillin-Resistant Staphylococcus aureus. AB - Silver nanoparticles (AgNPs) have been shown to be effective antibacterial agents against methicillin-resistant Staphylococcus aureus (MRSA). In this study, AgNPs were synthesized using Caesalpinia sappan extract as a reducing agent to convert Ag+ to AgNPs. Seven stabilizers (surfactants and polymers) were added during the reduction step to increase the colloidal stability and to enhance the antibacterial activity of the AgNPs. Spherical and amorphous particles were primarily observed, with estimated diameters ranging from 30.2 to 47.5 nm. X-ray diffraction confirmed the face centered cubic structures of the AgNPs. Among the employed stabilizers, the cationic surfactant cetyltrimethylammonium bromide (CTAB) exhibited the highest antibacterial activity against 19 strains of MRSA, followed by polyvinylpyrrolidone (PVP, average molecular weight of 10,000). In contrast, the anionic surfactants sodium dodecyl sulfate (SDS) and sodium dodecylbenzene sulfonate (NaDDBS) did not exhibit any significant antibacterial activity, suggesting that the cationic surfactant head group contributed to the higher antibacterial activity of the AgNPs against MRSA. PMID- 26369116 TI - Doxorubicin-Loaded Micelles Based on Folic Acid Conjugated pH-Dependent Thermo Sensitive Copolymer: In Vitro and In Vivo Evaluation. AB - In this paper, the doxorubicin (DOX)-loaded micelles were prepared based on a novel folic acid conjugated pH-dependent thermo-sensitive copolymer poly(D,L lactic acid)-b-poly(N-isopropyl methacrylamide-co-N-isopropylmaelic acid-co-10 undecenoic acid) (PLA-PNNUA-FA) constructed to provide an active targeting drug delivery and triggered drug release system. The micelles were able to target tumors through the interaction between folic acid and its receptors which are overexpressed on the tumor cell membrane, and achieved pH-dependent thermo induced drug release in the intracellular mild acidic media such as endosomes and lysosomes after the micelles enter the cells. The results of cell assays and animal experiments showed that the micelles exhibited obvious tumor penetration efficiency in vivo, also improved DOX cell uptake and cytotoxicity in vitro. It was suggested that copolymer PLA-PNNUA-FA might be a potential targeted drug carrier to deliver chemotherapeutic drugs achieving better efficacy of chemotherapy. PMID- 26369117 TI - Curcumin-Loaded Lipid Cubic Liquid Crystalline Nanoparticles: Preparation, Optimization, Physicochemical Properties and Oral Absorption. AB - In order to improve the oral absorption of curcumin, curcumin-loaded lipid cubic liquid crystalline nanoparticles were prepared and evaluated in vitro and in vivo. The hot and high-pressure homogenization method was used to prepare the nanoparticles. The formulation and process were optimized by uniform design with drug loading and entrapment efficiency as index, and physicochemical properties were also investigated. Spherical nanoparticles were observed under transmission electron microscope (TEM), with average particle size of 176.1 nm, zeta potential of -25.19 mV, average drug loading of (1.5 +/- 0.2)% and entrapment efficiency of (95 +/- 1.8)%. The in vitro release of curcumin from the nanoparticle formulation showed a sustained property, while the pharmacokinetics results after oral administration of curcumin loaded lipid cubic liquid crystalline nanoparticles in rat showed that the oral absorption of curcumin fitted one-compartment model and relative bioavailability was 395.56% when compared to crude curcumin. It can be concluded from these results that the lipid cubic liquid crystalline nanoparticles, as carriers, can markedly improve the oral absorption of curcumin. PMID- 26369118 TI - Nano-Aggregates of Doxorubicin-Conjugated Methoxy Poly(ethylene glycol)-b Carboxymethyl Dextran Copolymer. AB - Block copolymer composed of carboxymethyl dextran (CMDex) and methoxy poly(ethylene glycol) (MPEG) (abbreviated as CMDexPEG) was synthesized and doxorubicin (DOX) was conjugated with carboxyl groups of CMDexPEG. DOX-conjugated CMDexPEG block copolymer formed nanoparticles in water with sizes less than 100 nm. DOX-conjugated nanoparticles enhanced DOX delivery to the DOX-resistant CT26 cells and showed higher anticancer activity in vitro. DOX-conjugated nanoparticles inhibited growth of CT26 solid tumor at tumor-bearing mouse model study. In near infrared (NIR)-dye study, nanoparticles were retained in the tumor tissues for a longer period. PMID- 26369119 TI - Antioxidative Activity of Platinum Nanocolloid and Its Protective Effect Against Chemical-Induced Hepatic Cellular Damage. AB - Oxidative stress, a major cause of cellular injuries, is closely associated with a variety of chronic diseases such as cancer, liver diseases, degenerative brain disease and aging. In this study, we investigated antioxidant properties of platinum nanocolloid (PNC) against various oxidative stress conditions in vitro/in vivo by treating PNC on liver cell or tissue. Antioxidant activities of the PNC were determined by measuring quenching capacity on reactive oxygen species and its protective action against hydrogen peroxide or CCl4-induced oxidative cellular damage in HepG2 cell or liver tissue of mice. In vitro study, PNC markedly suppressed the production H2O2, .OH, alpha,alpha-diphenyl-beta picrylhydrazyl radical and nitric oxide in a dose-dependent manner. PNC also inhibited hydrogen peroxide-induced oxidative cellular damage in HepG2 hepatocytes. In vivo study with mice, PNC reduced hepatic lipid peroxidation and CCl4 induced toxicity. Our results support that platinum nanocolloid has antioxidant activities and protects hepatic cellular oxidative damage. Thus platinum nanocolloid may have a potential to be used as an antioxidant supplement. PMID- 26369120 TI - Protoporphyrin IX-Gold Nanoparticle Conjugates for Targeted Photodynamic Therapy- An In-Vitro Study. AB - Targeted drug delivery system using nanoparticles is a promising strategy for efficient Photodynamic therapy (PDT) as they have the potential to overcome the problems of photosensitizer and enhance the effectiveness and specificity of PDT. In this study, Protoporphyrin IX (PpIX) conjugated gold nanoparticles were synthesized using electrostatic and covalent conjugation scheme. Folic acid (FA) was also conjugated suitably to the covalent complex to vectorize the complex. Optical characterizations of the complex prove the formation of the complex. The size of the synthesized nanocomplexes was studied using light scattering measurements. The photo-toxicity of the free PpIX and PpIX-nanoparticle complexes were studied using MTT assay technique against Vero and HeLa cell lines. These In vitro results of this study indicates that, the nanoparticle complexes are more phototoxic compared to free PpIX, with the covalent complex being the better of the two complexes and the folate-mediated nanocomplex is the superior of the studied complexes. These results ensures that nanoparticle conjugated photosensitizers equipped with FA may be an effective drug delivery mechanism for PDT. PMID- 26369121 TI - Fabrication of 3D Scaffolds with Nano-Hydroxyapatite for Improving the Preosteoblast Cell-Biological Performance. AB - Three-dimensional (3D) scaffolds fabricated by rapid prototyping techniques have many merits for tissue engineering applications, due to its controllable properties such as porosity, pore size and structural shape. Nonetheless, low cell seeding efficiency remains drawback. In this study, poly-caprolactone (PCL) composite 3D extruded scaffolds were modified with nano hydroxyapatite (n-HAp). PCL/n-HAp 3D scaffold surface was treated with oxygen plasma to improve the preosteoblast cell seeding efficiency and proliferation. The results indicate that oxygen plasma is useful technique to improve the cell affinity. PMID- 26369122 TI - Determination of C-Terminal delta-Catenin Responsible for Inducing Dendritic Morphogenesis. AB - delta-Catenin induces dendritic morphogenesis in several cells and it was reported that deletion of C-terminal 207 amino acid of delta-catenin completely abolished the dendritic morphogenesis. However, exact domain responsible for inducing dendritic morphogenesis in C-terminus of delta-catenin was not mapped. Here, we report that expression of DeltaC47 (lacking 47 amino acid of C-terminus: 1-1200), DeltaC77 (lacking 77 amino acid of C-terminus: 1-1170) deletion mutants of delta-catenin induced the dendritic morphogenesis of HEK293T and NIH3T3 cells as full-length delta-catenin did. In agreement with previous report, DeltaC207 deletion mutant did not show the dendritic morphogenesis of the cells. Interestingly, introducing 107 amino acid deletion of C-terminus (DeltaC107 mutant: 1-1140) and 177 amino acid deletion of C-terminus (DeltaC177 mutant: 1 1070) showed limited primary and secondary dendritic process and notable spine like process formation. These results suggest that 1140-1170 amino acid of C terminal delta-catenin is required for primary and secondary dendrite-like process formation. PMID- 26369123 TI - In Vitro Evaluation of Hydroxyapatite-Coated Titanium Implant with Atmospheric Plasma Treatment. AB - Plasma treatments are becoming a popular method for modifying the characteristics of a range of substrate surfaces. Atmospheric pressure plasma (APP) is cost efficient, safe and simple compared to high-pressure plasma. This study examined the effects of a low-temperature APP treatment of a hydroxyapatite (HA)-coated Ti (HA-Ti) surface. The APP treatment made the HA-Ti surfaces more hydrophilic without changing surface morphologies. The APP-treated HA-Ti (APP-HA-Ti) surface showed enhanced cell spreading, cell proliferation, and alkaline phosphatase (ALP) levels with more developed cellular networks, and the formed extracellular matrix (ECM) was fused perfectly with the HA substrate than that on the HA-Ti surface. In conclusion, an APP treatment is a potential surface-modifying method that can enhance the cell affinity at the early stages in vitro. PMID- 26369124 TI - Ultrasensitive Detection and Subtyping of Porcine Endogenous Retrovirus Provirus Based on Magnetic Nanoparticles and Chemiluminescence. AB - Porcine endogenous retrovirus (PERV) is commonly integrated in pig genomes, and could cause a cross-species infection by xenotransplantation. In this study, we developed a rapid and ultrasensitive approach for detection and subtyping of PERV provirus based on magnetic nanoparticles (MNPs) and chemiluminescence (CL). The carboxylated MNPs (CMNPs) were covalently coupled with aminated probes for capturing biotinylated target fragments of PERV, the product of polymerase chain reaction (PCR). Agarose gel electrophoresis analysis approved the reliability of biotinylated fragments. The MNPs composites were incubated with streptavidin alkaline phosphatase (SA-ALP) and CL signal intensities were determined by subsequently adding 3-(2'-spiroadamantane)-4-methoxy-4-(3"-phosphoryloxy) phenyl 1,2-dioxetane (AMPPD). The optimal assay conditions of this approach were 1 mM for SA modification, 10 uM for probe modification, 55 (PERV), 54 (PERV-A), 50 (PERV-B), and 56 degrees C (PERV-C) for hybridization temperatures respectively, and 30 min for hybridization time. This approach was specific and highly sensitive, and the limit of detection (LOD) was 100 amol, which has the potential for screening out safe pig donors for xenotransplantation as well as to examine clinical samples from human patients treated with porcine xenotranplantation. PMID- 26369125 TI - The Inhibition of Escherichia coli Biofilm Formation by Gallium Nitrate-Modified Titanium. AB - Periprosthetic infections are notoriously difficult to treat due to biofilm formation. Previously, we reported that gallium-EDTA attached to PVC (polyvinyl chloride) surface could prevent bacterial colonization. Herein we examined the effect of this gallium-EDTA complex on Escherichia coli biofilm formation on titanium. It was clearly demonstrated that gallium nitrate significantly inhibited the growth and auto-aggregation of Escherichia coli. Furthermore, titanium with gallium-EDTA coating resisted bacterial colonization as indicated by crystal violet staining. When the chips were immersed in human serum and incubated at 37 degrees C, they demonstrated significant antimicrobial activity after more than 28 days of incubation. These findings indicate that gallium-EDTA coating of implants can result in a surface that can resist bacterial colonization. This technology holds great promise for the prevention and treatment of periprosthetic infections. PMID- 26369126 TI - 660 nm Red LED Induces Secretory Leukocyte Protease Inhibitor (SLPI) in Lipopolysaccharide-Stimulated RAW264.7 Cell. AB - SLPI acts as a modulator of the innate immune responses of macrophages, neutrophils and odontoblasts, and LPS-inducible anti-inflammatory cytokine to suppress the production of pro-inflammatory products by macrophages. Many studies have revealed the effects of light emitting diodes (LEDs) on the tissue repair and inflammatory responses. Although the anti-inflammatory mechanisms of irradiation with LEDs in gingival fibroblasts are known, the effects of 660 nm red LEDs on the inflammation remain unclear. Moreover, there is no report regarding the molecular mechanism for the relationship between SLPI and biological effects of LEDs. The effects of 660 nm red LEDs on inflammation with SLPI were investigated by examining the effects of 660 nm LED on the SLPI expression of RAW264.7 cells after LPS stimulation. This paper reports that the 660 nm red LED induced SLPI expression or reduced the LPS response, and inhibited NF-kappaB activation directly, leading to the suppression of pro-inflammatory cytokines, such as TNF-alpha and IL-1beta, suggesting that it might be a useful wavelength LED for inflammation therapy. PMID- 26369127 TI - Cytotoxicity of Gold Nanorods and Nanowires on Cultivated Neural Precursor Cells. AB - Given the emergence of nanotherapeutics and nanodiagnostics as key tools in today's medicine, it has become of critical importance to define the interactions of nanomaterials with biological systems. The biomedical applications of nanoparticles (NPs) in chemical sensing, biological imaging, drug delivery, photothermal therapy and cancer treatment have been demonstrated. Gold NPs as new biomedical tools are the focus of research due to their ease of synthesis, chemical stability and unique optical properties. Therefore, there is a need to establish the toxicity, side effects and safety of gold NPs for human applications. To study the in vitro cytotoxicity of gold NPs, we performed MTT assay using two types of gold NPs such as gold nanorods (GNRs) and gold nanowires (GNWs). The percentage cytotoxicity of damaged neural precursor cells (NPCs) that were treated with 100 mg GNRs was 97.5+/-3.9%; and proportion of damaged NPCs following the administration of the same dose of GNWs was 98.8+/-0.3%. The cytotoxicity of 10 mg GNRs in NPCs was 54.4+/-8.3%, whereas it was 98.7+/-0.6% for the same dose of GNWs. Then, to verify that gold NPs induced apoptotic cell death in NPCs, the LIVE/DEAD Viability/Cytotoxicity assay was performed. We observed that cell death of NPCs increased with an increase in quantity of both types of gold NPs. Cell viability assessed the overall dose-dependent toxicity of NPs in cultured cells. As the results suggest, this study demonstrated that treatment with gold NPs resulted in cellular toxicity in a dose-dependent manner in cultured NPCs. PMID- 26369128 TI - Plasma Polymerization of 1,2-Diaminocyclohexane for Covalent Bonding of Bone Morphogenic Protein-2 on Titanium Surface. AB - Among the bone morphogenic protein (BMP) family members, BMP-2 is a potent osteoinductive factor that plays key roles during bone formation. In this study, plasma polymerization of 1,2-diaminocyclohexane (DACH) was performed to immobilize the BMP-2 on Ti surface. The plasma polymerization of DACH was carried out at a discharge power of 60 W and 100 W under a pressure of 10 mTorr for 90 sec. The BMP-2 was successfully immobilized on the DACH plasma treated Ti surface. The BMP-2 immobilized Ti surface showed the excellent cell differentiation. The results indicate that the DACH plasma polymerized Ti surface has a potential for immobilization of biomolecules in bone tissue engineering. PMID- 26369129 TI - Controlled Release of Linalool Using Nanofibrous Membranes of Poly(lactic acid) Obtained by Electrospinning and Solution Blow Spinning: A Comparative Study. AB - The controlled-release of natural plant oils such as linalool is of interest in therapeutics, cosmetics, and antimicrobial and larvicidal products. The present study reports the release characteristics of linalool encapsulated at three concentrations (10, 15 and 20 wt.%) in poly(lactic acid) nanofibrous membranes produced by electrospinning and solution blow spinning (SBS) as well as the effect of linalool on fiber morphology and structural properties. PLA nanofibrous membranes were characterized by Scanning Electron Microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD) and contact angle measurements. The average diameters of the electrospun and solution blow spun nanofibers were similar, ranging from 176 to 240 nm. Linalool behaved as a plasticizer to PLA decreasing the glass transition temperature (Tg), melting point (Tm) and crystallization temperature (TC) of PLA. Curves of the release of linalool at 35 degrees C were non-linear, showing a clear biphasic pattern consistent with one or more Fickian release components. The time required to release 50% of linalool (t1/2) decreased with increasing linalool concentration. The range in t1/2 values for SBS nanofibers was higher (291-1645s) than the t1/2 values for electrospun fibers (76-575s). PMID- 26369130 TI - Perfluorodecalin-Filled Poly(n-butyl-cyanoacrylate) Nanocapsules as Potential Artificial Oxygen Carriers: Preclinical Safety and Biocompatibility. AB - With regard to the development of artificial blood substitutes, perfluorodecalin filled poly(n-butyl-cyanoacrylate) nanocapsules are already discussed for the use as artificial oxygen carriers. The aim of the present study was to thoroughly investigate the preclinical safety and biocompatibility of the perfluorodecalin filled poly(n-butyl-cyanoacrylate) nanocapsules prepared by interfacial polymerization. Nanocapsules were assessed for physical and microbial stability. Subsequent to intravenous infusion to anesthetized rats, effects on systemic parameters, microcirculation, circulatory in vivo half-life, acid base/metabolic status, organ damage and biodistribution were evaluated using inter alia 19F-NMR spectroscopy and in vivo microscopy. Perfluorodecalin-filled poly(n-butyl cyanoacrylate) nanocapsules displayed physical and microbial stability over a period of 4 weeks and the circulatory in vivo half-life was t1/2 = 30 min. In general, all animals tolerated intravenous infusion of the prepared nanocapsules, even though several side-effects occurred. As a consequence of nanocapsule infusion, a transient decrease in mean arterial blood pressure, impairment of hepatic microcirculation, organ/tissue damage of liver, spleen and small intestine, as well as an elevation of plasma enzyme activities such as lactate dehydrogenase, creatine kinase and aspartate aminotransferase could be observed. The assessment of the distribution pattern revealed nanocapsule accumulation in spleen, kidney and small intestine. Perfluorodecalin-filled poly(n-butyl cyanoacrylate) nanocapsules conformed to basic requirements of drugs under preclinical development but further improvement is needed to establish these nanocapsules as novel artificial oxygen carriers. PMID- 26369131 TI - Biotransformation and Its Application: Biogenic Nano-Catalyst and Metal-Reducing Bacteria for Remediation of Cr(VI)-Contaminated Water. AB - The use of ubiquitous metal-reducing bacteria (MRB) and the synthesis and transforming capability of nano-sized catalysts (BNC) provide enormous potential for the transformation of environmental waste to environmental catalysts, such as abandoned mine precipitates that are transformed into nontoxic and inexpensive catalysts for remediating contaminated groundwater. In this study, BNC from acid mine drainage (AMD) precipitates are transformed to nm-sized siderite after a fermenting process under anaerobic conditions, and MRB enriched from inter-tidal flat sediments were examined for efficiency in the Cr(VI) reduction and immobilization in upward flow-through sand column tests. As a result, BNC and MRB proved to have excellent Cr(VI) reducing/immobilizing capacity independently and when used in conjunction. In addition the combination of BNC+MRB showed to have a capacity enhanced with 20% more capability of Cr(VI) reduction and immobilization in flow-through column test for 168 h. PMID- 26369132 TI - Preparation of O2 Plasma Treated Polycaprolactone/Nano TiO2 Composites and In Vitro Bioactivity. AB - Polycaprolactone (PCL)/TiO2 composite films (PTCFs) were prepared by a solvent casting method at various concentrations of TiO2 (1, 3, 5, and 10 wt%) and then treated using oxygen plasma. The hydrophilicity of the oxygen plasma treated PTCFs increased as the treatment time was increased, due to the oxygen induced production of polar species at the surface of the PTCFs. In vitro bioactivities of the composite films were examined by immersion in simulated body fluid for up to 7 days. It was found that the oxygen plasma treatment significantly influenced the in vitro bioactivity of the PTCFs. PMID- 26369133 TI - Liquid Crystal Formulation and Optimization of Anti-Microbial Polyherbal Ointment. AB - We examined the formulation of liquid crystalline systems (LCS) including 5% TSE extracts and analyzed marker substances of the 5% TSE ointment by HPLC-DAD. The TSE extracts were evaluated for its anti-bacterial activity against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Candida albicans. We found the extracts showed predominant activity against selected bacterial species. The result of the polarized light microscopy, differential scanning calorimetry (DSC), small-angle X-ray diffraction (SXRD), and rheology analysis indicated the presence of LCS structures with lamellar arrangement. DSC of the TSE formulas showed higher transition peak temperature at 60 degrees c for the phase. SXRD observation of the LCS formulas showed that the structures of the LCS formulas were in the lamellar liquid crystalline phase. Further, to ensure the quality and purity of the TSE ointment, HPLC analysis was performed by measuring the. content of 2 marker substances. The contents of marker substances in the TSE ointment were calculated as 0.078% (paeoniflorin) and 0.031% (glycyrrhizin), respectively. Taken altogether, our study report successful generation of LCS made of 5% TSE ointment and its antimicrobial activity. Moreover, the quantitation of the two active components enable a proper quality control of the TSE extracts, that is essential for the development of ointment products. PMID- 26369134 TI - Ethosomes and Transfersomes for Topical Delivery of Ginsenoside Rhl from Red Ginseng: Characterization and In Vitro Evaluation. AB - Red ginseng (the steamed root of Panax ginseng C. A. Mayer), which contains ginsenosides as its main constituents, is frequently used to treat tumor, inflammation, diabetes, stress and acquired immunodeficiency syndrome in Asian countries. Ginsenoside Rhl, a bacterial metabolite of ginsenoside Rgl, is a protopanaxatriol type of ginsenosides. Liposomes do not deeply penetrate the skin and remain confined to the stratum corneum.Thus, new vesicular colloidal carriers such as ethosomes and transfersomes have been developed as an enhanced type of liposomes, recently. The aim of this study was to improve the topical delivery of ginsenoside Rhl isolated from red ginseng employing new vesicular system of ethosomes and transfersomes compared to conventional liposome. Characterization of ginsenoside Rhl-loaded vesicles were prepared and evaluated for particle size, zeta potential, entrapment efficiency (% EE), and transmission electron microscopy (TEM) studies. In addition, skin permeation profile was obtained using frantz diffusion cells and rat dorsal skin treated with ethosome and transfersome compared with conventional iposome. The size of vesicles range from 108.5 to 322.9 nm, and negatively charged from -20.95 to -31.37 mV. The % EE of ginsenoside Rh1 was obtained between 45.0 to 65.0%. Transfersomes provided a significantly higher skin permeation of ginsenoside Rhl compared to ethosome and conventional liposome. Therefore, based on the current study, ginsenoside Rhl loaded transfersomes can act as a topical therapeutic effects potential. PMID- 26369135 TI - The Effect of Thymosin beta4 for Osteoblast Adhesion on Titanium Surface. AB - Titanium (Ti) is the most widely used implant material in dentistry and orthopedics but the release of metal ions from Ti implants results in increased bone resorption by enhancing the production of inflammatory cytokines from the macrophages and facilitating osteoclast differentiation. Thymosin beta4 (Tbeta4) has several biological activities, such as promoting wound healing, angiogenesis, cell proliferation and migration in mammalian cells. This study examined the role of Tbeta4 in osteoblasts via focal adhesions (FAs) and ERK1/2 signaling related to cell adhesion and proliferation for cell survival on the Ti surface. As a result, cell adhesion and proliferation increased in the Tbeta4 treated cells (Tbeta4/MC3T3-E1) but was significantly lower in the Tbeta4 knock-down cells by Tbeta4-siRNA (si-Tbeta4/MC3T3-E1) than that of the untreated cells. The levels of FAK phosphorylation, paxillin expression, and paxillin localization were higher in the Tbeta4/IMC3T3-E1 cells than that of the untreated cells but lower in the si-Tbeta4/MC3T3-E1 cells. In addition, the levels of cell proliferation, Grb2 and Ras protein expression and phosphorylation of ERK1/2 were higher in the Tbeta4/MC3T3-E1 cells than in the untreated cells but lower in the si Tbeta4/IMC3T3-E1 cells. These results suggest that Tbeta4 might be a good nanomolecule that promotes osteoblast survival by facilitating adhesion and proliferation on the Ti surface. PMID- 26369136 TI - Characterizations of Bone-Like Apatite Powder Fabricated Using Modified Simulated Body Fluid. AB - The objective of this study is to fabricate bone-like apatite (BLAp) powder using the modified simulated body fluid (SBF). The SBF2X and SBF4X groups were prepared by increasing the concentration of inorganic ions by two and four times, respectively, to that of the standard SBF. The mSBF4X group was prepared by particularly increasing the concentrations of calcium and phosphate ions in SBF. Bovine serum albumin (BSA) was added for SBF2X-BSA, SBF4X-BSA, and mSBF4X-BSA groups. BLAp powders were precipitated in these SBFs while being kept at 60 degrees C. Micro-morphology of BLAp powders showed tens of micrometers-sized rounded clusters which composed with sheet-like nano crystallites. The radius of BLAp clusters were decreased by increasing the concentration of inorganic ions and by incorporating the BSA. The hydroxyapatite crystalline structure was dominant for all sample groups. Further, octacalcium phosphate structure was detected in the mSBF4X group. However, these peaks were decreased in mSBF4X-BSA. FT-IR spectra demonstrated that BSA was co-precipitated in BLAp crystallites, and the amount of BSA was higher in the mSBF4X-BSA group than in the SBF4X-BSA group. PMID- 26369137 TI - Fabrication and Characterization of Antimicrobial Ethyl Cellulose Nanofibers Using Electrospinning Techniques. AB - Ethyl cellulose nanofibers were fabricated by electrospinning techniques using ethyl cellulose solution having concentrations of 150 g/l, using different volume ratios of a binary THF (tetrahydrofuran): DMAc (N,N dimethylacetamide) solvent system. The influence of the composition of the binary solvent system on the surface morphology of ethyl cellulose nanofibers with or without adhered antibiotics was investigated using field emission scanning electron microscope (FE-SEM). To assess the effectiveness of drug release from the nanofibers and their antibacterial activities toward S. aureus, streptomycin was selected as the antibiotic. Disc diffusion and optical density tests were used for the assessment. The antibiotic release from ethyl cellulose fibers was best when the THF to DMAc volume ratio was 3 to 2 (v/v). The optical density test showed the antibacterial effective time of the streptomycin antibiotics loaded in nanofibers was longer than that of the bulk antibiotics against S. aureus bacteria. PMID- 26369138 TI - A Facile Synthesis and Thermal Properties of Graphene Oxide-Mischmetal Oxide Nanocomposites. AB - In this work, we have reported the facile synthesis, characterizations and thermal analyses of Graphene Oxide (GO) and Mischmetal Oxide (MmO) composites. To the best of our knowledge, this is the first report for graphene oxide and mischmetal oxide composites. The elemental compositional analysis of as synthesized mischmetal oxides are O-16.10 wt.%, Gd-02.80 wt.%, La-20.60 wt.%, Ce 41.10 wt.%, Pr-03.80 wt.% and Nd-15.40 wt.%. The SEM analysis reveals that the mischmetal oxide particles are anchored on the large surface area of graphene oxide. Thermal stability and activation kinetics of graphene oxide and GO-MmO composites are studied by thermo gravimetric analysis (TGA) and differential scanning calorimeter (DSC). The DSC results reveal that the initial reaction temperature and activation energies are decreased for GO-MmO composites compared with graphene oxide. The activation energies (calculated by Kissinger equation) are 107.25 kJ/mol and 137.61 kJ/mol for GO-MmO composites and graphene oxide, respectively. Improving the thermal stability and decreasing the activation energy are due to the synergistic effect of mischmetal oxide. PMID- 26369139 TI - Manganese Dioxide/Reduced Graphene Oxide with Poly(3,4-ethylenedioxythiophene) for Improved Electrocatalytic Oxygen Reduction Reaction. AB - Poly(3,4-ethylenedioxythiophene)-(PEDOT)-functionalized reduced graphene oxide (rGO) with MnO2 nanoparticles (MnO2/PEDOT/rGO) was prepared using electrochemical methods. The MnO2/ PEDOT/rGO was obtained through the electrochemical reduction of PEDOT/GO and under electrochemical treatment in KMnO4. The PEDOT/rGO and MnO2/PEDOT/rGO were characterized by several instrumental and electrochemical methods. The electrocatalytic 02 reduction for both electrodes was investigated via cyclic and hydrodynamic voltammetry in 0.1 M KOH aqueous solutions. The kinetic analysis in comparison to PEDOT/rGO a significant enhancement was found for the MnO2/PEDOT/rGO. The proposed main path in the oxygen reduction reaction (ORR) mechanism on the MnO2/PEDOT/rGO was the direct four-electron transfer process with faster transfer kinetic rate. The better ORR kinetics were obtained due to the excellent composite formation and well attachment of MnO2 NPs within oxide form. The PEDOT/rGO was less stable for long term use than MnO2/PEDOT/rGO. PMID- 26369140 TI - Synthesis of Electrochemically Reduced Graphene Oxide Bonded to Thiodiazole-Pd and Applications to Biosensor. AB - A novel biosensor for the determination of hydrogen peroxide and glucose was developed based on EGN-TDZ-Pd, as an electrocatalyst. The preparation of graphene oxide (GO) nanosheets was functionalized by combining it with 5-amino-1,3,4 thiadiazole-2-thiol (TDZ) and by covalently bonding it to palladium (Pd) nanoparticles (GO-TDZ-Pd). In the electrochemical investigation, EGN-TDZ-Pd was characterized via scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), and electrochemical impedance spectroscopy (EIS). Cyclic voltammetry (CV) and chronoamperometry (CA) were used to characterize the performance of EGN-TDZ-Pd. The proposed H2O2 biosensor exhibited a wide linear range from 10 uM to 6.5 mM. Also, a glucose biosensor was prepared using glucose oxidase and EGN-TDZ-Pd placed onto a glassy carbon electrode (GCE). The GOx/EGN-TDZ-Pd/GCE was easily prepared using a rapid and simple procedure, and it was utilized for highly sensitive glucose determination. PMID- 26369141 TI - Electrocatalytic Oxidation of Formic Acid in an Alkaline Solution with Graphene Oxide- Supported Ag and Pd Alloy Nanoparticles. AB - The electrocatalytic activities of metal-decorated graphene oxide (GO) catalysts were investigated. Electrochemically reduced GO-S-(CH2)4-S-Pd [ERGO-S-(CH2)4-S Pd] and GO-S-(CH2)4-S-PdAg alloy [ERGO-S-(CH2)4-S-PdAg] were obtained through the electrochemical reduction of GO-S-(CH2)4-S-Pd and GO-S-(CH2)4-S-PdAg in a pH 5 PBS solution. It was demonstrated that the application of ERGO-S-(CH2)4-S-Pd and ERGO-S-(CH2)4-S-PdAg used in a modified GCE improves the electrocatalytic oxidation of formic acid. The addition of an Ag nanoparticle with a carbon chain Pd in the electrode provides an electrode with very interesting properties for the electrocatalytic oxidation of formic acid. The ERGO-S-(CH2)4-S-Pd and ERGO-S (CH2)4-S-PdAg were characterized via X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). ERGO-S-(CH2)4-S-Pd and ERGO-S-(CH2)4-S-PdAg can be employed for the electrocatalytic oxidation of formic acid. The electrochemical behaviors of this electrode were investigated using cyclic voltammetry (CV), chronoamperometry (CA) and electrochemical impedance spectroscopy (EIS). PMID- 26369142 TI - Benzocyclobutene (BCB) Polymer as Amphibious Buffer Layer for Graphene Field Effect Transistor. AB - Owing to the scattering and trapping effects, the interfaces of dielectric/graphene or substrate/graphene can tailor the performance of field effect transistor (FET). In this letter, the polymer of benzocyclobutene (BCB) was used as an amphibious buffer layer and located at between the layers of substrate and graphene and between the layers of dielectric and graphene. Interestingly, with the help of nonpolar and hydrophobic BCB buffer layer, the large-scale top-gated, chemical vapor deposited (CVD) graphene transistors was prepared on Si/SiO2 substrate, its cutoff frequency (fT) and the maximum cutoff frequency (fmax) of the graphene field-effect transistor (GFET) can be reached at 12 GHz and 11 GHz, respectively. PMID- 26369143 TI - Coordinated Fast Synthesis of Electrocatalytic Palladium Nanoparticles Decorated Graphene Oxide Nanocomposite for Fuel Cell. Applications. AB - Reduced graphene oxide and palladium nanoparticle (r-GO/Pd) nanocomposites were synthesized by an ecofriendly one-pot solid-state reduction method using ascorbic acid as a reducing agent. The coordinated formation of r-GO/Pd nanocomposite was observed within 2 min. The formed Pd nanoparticles (5 nm size) were uniformly distributed over the r-GO as characterized by X-ray powder diffraction, raman spectroscopy, scanning electron microscopy equipped with energy dispersive X-ray spectroscopy, and transmission electron microscopy. The cyclic voltammetric study revealed that the r-GO/Pd nanocomposite exhibited excellent electrocatalytic behavior toward the oxidation of alcohols in an alkaline medium. Our study proposes a cost-effective, easy, rapid, scalable, and environmentally friendly method for the synthesis of GO/metal nanoparticles hybrid catalytic material for electrochemical energy applications. PMID- 26369144 TI - Electrical Properties of Conductive Nylon66/Graphene Oxide Composite Nanofibers. AB - In this paper, we report on the structural and electrical properties of graphene oxide (GO) incorporated Nylon66 (N66) composite nanofibers prepared via electrospinning technique. Different types of composite nanofibers were electrospun by varying the weight percentage of GO in the polymer solution. Scanning electron microscopy, X-ray diffraction and Fourier transform infrared spectroscopy, as well as current-voltage (I-V) measurements were used to characterize the N66/GO composite nanofibers. The morphology of the N66/GO composite nanofibers exhibited densely arranged mesh-like ultrafine nanofibers which were strongly bound in between the main fibers. The I-V characteristics of the N66/GO composite nanofibers demonstrated that the blending of GO in to N66 nanofibers led to a dramatic improvement of the electrical conduction compared to that of pristine N66 nanofibers which can be utilized for the various technological applications. PMID- 26369145 TI - Evaluation of the Influence of Modified TiO2 Particles on Polypropylene Composites. AB - This article reports the preparation of composites and nanocomposites of polypropylene and titanium dioxide particles, with our without surface modification, to obtain photodegradable or photostable materials with less severe environmental impacts. The modification of the titanium dioxide was carried out in the laboratory using propionic acid to improve the interaction of titanium dioxide with the polymer matrix. The composites and nanocomposites were prepared by melt extrusion using a single-screw extruder. The materials obtained were characterized by nuclear magnetic resonance relaxometry, X-ray diffraction, Raman spectroscopy, thermogravimetric analysis and mechanical analysis (tension). The results showed that the surface modification of the titanium dioxide particles promoted their better dispersion, distribution and interaction with the polypropylene matrix, generating a nanocomposite material. The NMR relaxometry results showed that the modified particles changed the molecular dynamics, indicating the formation of nanocomposites. In the Raman spectra, peaks related to the titanium dioxide only appeared at a concentration of 1%, and there was an inversion between crystalline and amorphous phase regions in the samples with the organophilic titanium dioxide, indicating the formation of a nanocomposite. The best modified PP/TiO2 compositions were those containing 0.25 and 0.50% modified TiO2 particles. The incorporation of the titanium dioxide particles, in rutile form, promoted photostabilization of the composites and nanocomposites at all ratios, and the composition containing 0.50% modified TiO2 presented the best photostabilization. PMID- 26369146 TI - Nano-Snowflower of Gold Nanoparticles-Ruthenium Metallopolymer-Carbon Nanotubes Binding Anti-DNP IgE Antibody. AB - Gold nanoparticles (AuNPs) have been chemically functionalized onto multiwalled carbon nanotubes (MWCNT) through a metallopolymer linker-bis (2,2':6'2" terpyridine) ruthenium(II)-connected diblock poly(N-isopropyacryamide). A "nano snowflower" pattern was formed by self-assembly MWCNT-AuNP nanocomposite with anti-DNP IgE antibody. MWCNT-AuNP nanohybrid has unique biocompatibility and electronic current-voltage properties. This nanohybrid shows the potential application for IgE biosensor to diagnose cancer cells. We represent a step towards building complex electronic circuits response by providing molecular recognition properties. PMID- 26369147 TI - The Influence of Particle Shapes on Strength and Damage Properties of Metal Matrix Composites. AB - The influence of the distribution of particle shapes, locations and orientations on the mechanical behavior of the particle reinforced Metal-Matrix Composite (MMC) is studied through finite element (FE) method under different loading conditions in this investigation. The FE-model with multi-particle is generated through the random sequential adsorption algorithm, with the particles treated respectively as elastic-brittle circular, regular octagon and hexagon and square shape. Ductile failure in metal matrix, brittle fracture of particles and interface debonding are taken into account during the simulations. 2D cohesive element is applied to simulate the debonding behavior of interface. The damage models based on the stress triaxial indicator and maximum principal stress criterion are developed to simulate the ductile failure of metal matrix and brittle cracking of particles, respectively. Simulation results show that the interface debonding dominates the failure process under the loading, while the damage in particle grows at slowest rate compared with those in matrix and interface. PMID- 26369148 TI - Controlled Synthesis of Functional Silver Nanoparticles Dispersible in Aqueous and Non-Aqueous Medium. AB - The synthesis of silver nanoparticles (AgNPs) controlled by active participation of 3-Amino-propyltrimethoxysilane (3-APTMS) and 3-Glycidoxypropyltrimethoxysilane (GPTMS) is found to be function of two sequential processes; (1) interaction of metal ions with 3-APTMS and (2) interaction of GPTMS with 3-APTMS capped metal ions. The mechanism of such process as evidenced from visual photographs, UV visible spectroscopy, energy dispersive X-ray spectroscopy (EDX) and transmission electron microscopy (TEM) is reported. The experimental findings demonstrate the followings; (1) There is faster interaction of 3-APTMS with gold ions as compared to that of silver ions under similar conditions, (2) Methanolic solution of GPTMS undergo interaction with 3-APTMS and the same is facilitated in the presence of 3 APTMS treated silver ions, (3) The size of as synthesized AgNPs increases with an increase in 3-APTMS concentration whereas reverse is recorded for change in GPTMS concentration, (4) The molar ratio of 3-APTMS/GPTMS control the nanogeometry as well as the dispersibility of AgNPs in both aqueous and non aqueous media, (5) The dispersion ability of AgNPs is attributed to the hydrophobic alkyl chain of the reaction product of GPTMS and 3-APTMS (6) AgNPs shows absorption maxima as a function of refractive index of the medium and (7) The as synthesized AgNPs behave as peroxidase mimetic in both aqueous and non-aqueous medium justifying the potential typical applications. PMID- 26369149 TI - Effect of Eu1+ and A13+ Concentrations on Photoluminescence of Gd2O3:Eu3+. AB - Gd2O3:Eu3+Al3+ phosphors are synthesized by wet chemical method and its photoluminescence properties are studied at different concentrations of Eu3+ and A13+. In emission spectra, the dominant peak observed at 611 nm corresponds to hypersensitive electric dipole transition in Eu3+. For Eu3+ concentration of 0.02, a good emission profile is observed and further its emission studies are carried out for the phosphor annealed at different temperatures and with the addition of A13+. The critical distance between the luminescent center is calculated to study the concentration quenching phenomenon. Enhancement of energy transfer occurs on introducing Al3+ in Gd2O3:Eu3+ phosphor. CIE coordinates are also calculated for Gd2O3:Eu3+ A13+ to estimate the color purity of the phosphor. PMID- 26369150 TI - Microwave Assisted Synthesis of Ferrite Nanoparticles: Effect of Reaction Temperature on Particle Size and Magnetic Properties. AB - The preparation of ferrite magnetic nanoparticles of different particle sizes by controlling the reaction temperature using microwave assisted synthesis is reported. The iron oxide nanoparticles synthesized at two different temperatures viz., 45 and 85 degrees C were characterized using techniques such as X-ray diffraction (XRD), small angle X-ray scattering (SAXS), vibrating sample magnetometry (VSM), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR). The average size of iron oxide nanoparticles synthesized at 45 and 85 degrees C is found to be 10 and 13.8 nm, respectively, and the nanoparticles exhibited superparamagantic behavior at room temperature. The saturation magnetization values of nanoparticles synthesized at 45 and 85 degrees C were found to be 67 and 72 emu/g, respectively. The increase in particle size and saturation magnetization values with increase in incubation temperature is attributed to a decrease in supersaturation at elevated temperature. The Curie temperature was found to be 561 and 566 0C for the iron oxide nanoparticles synthesized at 45 and 85 degrees C, respectively. The FTIR spectrum of the iron oxide nanoparticles synthesized at different temperatures exhibited the characteristic peaks that corresponded to the stretching of bonds between octahedral and tetrahedral metal ions to oxide ions. Our results showed that the ferrite nanoparticle size can be varied by controlling the reaction temperature inside a microwave reactor. PMID- 26369151 TI - Time Resolved Spectroscopic Studies on a Novel Synthesized Photo-Switchable Organic Dyad and Its Nanocomposite Form in Order to Develop Light Energy Conversion Devices. AB - UV-vis absorption, steady state and time resolved spectroscopic investigations in pico and nanosecond time domain were made in the different environments on a novel synthesized dyad, 3-(2-methoxynaphthalen-1-yl)-1-(4-methoxyphenyl)prop-2-en 1-one (MNTMA) in its pristine form and when combined with gold (Au) nanoparticles i.e., in its nanocomposite structure. Both steady state and time resolved measurements coupled with the DFT calculations performed by using Gaussian 03 suit of software operated in the linux operating system show that though the dyad exhibits mainly the folded conformation in the ground state but on photoexcitation the nanocomposite form of dyad prefers to be in elongated structure in the excited state indicating its photoswitchable nature. Due to the predominancy of elongated isomeric form of the dyad in the excited state in presence of Au Nps, it appears that the dyad MNTMA may behave as a good light energy converter specially in its nanocomposite form. As larger charge separation rate (kcs ~ 4 x 10(8) s-1) is found relative to the rate associated with the energy wasting charge recombination processes (kcR ~ 3 x 10(5) s-1) in the nanocomposite form of the dyad, it demonstrates the suitability of constructing the efficient light energy conversion devices with Au-dyad hybrid nanomaterials. PMID- 26369152 TI - Catalytic Activities for Glucose Oxidation of Au/Pd Bimetallic Nanoparticles Prepared via Simultaneous NaBH4 Reduction. AB - Au/Pd bimetallic nanoparticles (BNPs) were prepared by simultaneous reduction method using NaBH4 as a reducing reagent. The effects of particle size, electronic structure and composition upon the catalytic activities of the BNPs for aerobic glucose oxidation were investigated. The PVP-protected Au/Pd BNPs of about 2.0 nm in diameter synthesized via rapid injection of NaBH4 possessed a high catalytic activity for aerobic glucose oxidation. The catalytic activity of BNPs with the Au/Pd atomic ratio of 60/40 was more than two times higher than that of Au nanoparticles (NPs) though the latter were smaller. This can be ascribed to the presence of negatively charged Au atoms arisen from electron donation from neighboring Pd atoms via electronic charge transfer. In contrast, Au/Pd BNPs synthesized via dropwise addition of NaBH4 into the starting solution and having the large mean particle sizes, showed a low catalytic activity. PMID- 26369153 TI - Microbial Synthesis of Iron Sulfide (FeS) and Iron Carbonate (FeCO3) Nanoparticles. AB - This study examined mineral transformations during anoxic bioreduction of iron hydroxide and iron oxyhydroxysulfate found in acid mine drainage (AMD) into iron sulfide (FeS) and siderite (FeCO3) nanoparticles. Glucose (10 mM) was inoculated into AMD to stimulate indigenous bacterial growth for bioreduction of Fe(III) containing minerals. Changes in microbial, geochemical, and mineralogical characteristics were monitored via 16S rRNA, XRD, SEM-EDX, TEM-EDX, ICP-AES, and IC analyses. The AMD was found to be rich in elements, including Fe, Al, Mn, Na, and S (SO4), and had a pH of 5.2. The mineral contents mainly consisted of Fe(III)-containing minerals, such as schwertmannite [Fe8O8 (OH)8-2x(SO4)x . nH2O] and akaganeite [beta-FeO(OH)]. During anoxic bioreduction of AMD, the Fe(III) containing minerals were transformed by indigenous iron-reducing bacteria (e.g., Geobactersp.) into Fe(II)-containing minerals, such as iron sulfide (FeS) and iron carbonate, siderite (FeCO3), within 3-4 days. The microbially-formed iron sulfide (FeS) and siderite (FeCO3) were of 40-60 nm and 10 nm-3 um in size, respectively. These results not only show that indigenous iron-reducing bacteria in AMD can aid or accelerate formation of Fe(II)-containing minerals when under anoxic environments, but can also offer a simple method for microbial synthesis of nano-sized Fe(II)-containing minerals that can be used as catalysts for environmental remediation by recycling AMD. PMID- 26369154 TI - Synthesis of Uniform CdSe Quantum Wires via Oriented Attachment. AB - In this work, a facile and catalyst-free method is developed to synthesize CdSe quantum wires (QWs) in organic solvent. Analysis on the intermediate products reveals that assembly of the initially-formed magic-sized CdSe clusters via oriented attachment plays a crucial role for generation of the well-defined QWs. Due to its simplicity, this method can be extended to production of many types of semiconductor QWs. PMID- 26369155 TI - Carbon Fiber Grafted with Nanodiamond: Preparation and Characterization. AB - Nanodiamonds have recently attracted great attention because of their outstanding hardness in combination with excellent wear resistance. Chemistry modification of the surface and incorporation into a material are required in many applications. In this report, Nanodiamond particles were firstly reduced and two different approaches were used to prepare carbon fiber grafted with nano-diamond. Nanodiamonds functionalized with hydroxyl and amino groups via chemical modification were successfully introduced into the functionalized carbon fiber surface by covalent bonds. The modification of the carbon fibers was characterized using Fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM), energy-dispersive X-ray spectroscopy (EDX), X-ray photoelectron spectroscopy (XPS) and Wide-angle X-ray diffraction (WAXD). BET surface area of the carbon fibers was increased by about 58% compared with the unmodified fibers. PMID- 26369156 TI - Selective Oxidation of n-Hexane by Cu (II) Nanoclusters Supported on Nanocrystalline Zirconia Catalyst. AB - Cu (II) nanoclusters supported on nanocrystalline zirconia catalyst (with size ~15 nm), was prepared by using cationic surfactant cetyltrimethylammonium in a hydrothermal synthesis method. The catalyst was characterized by XRD, XPS, TGA, SEM, TEM, FTIR and ICP-AES. The catalyst was found to be efficient in selective oxidation of n-hexane to 2-hexanol. An n-hexane conversion of 55%, with a 2 hexanol selectivity of 70% was achieved over this catalyst in liquid phase, without the use of any solvent. The catalyst can be reused several times without any significant activity loss. PMID- 26369157 TI - Preparation of Polyacrylonitrile/Ferrous Chloride Composite Nanofibers by Electrospinning for Efficient Reduction of Cr(VI). AB - In this study, A novel adsorbent material of polyacrylonitrile (PAN)/ferrous chloride (FeCl2) composite nanofibers is prepared by electrospinning, a simple and effective method. The obtained composite nanofibers have a non-uniform morphology and structure and a large specific surface area of 13.8 m2 g-1. Fourier transform infrared spectroscopy (FTIR) revealed that Fe2+ was successful introduced into the composite nanofibers. Furthermore, the PAN/FeC12 composite nanofibers exhibited excellent performance in Cr removal, especially when reacted with reduction from a Cr(VI) standard containing solution, which has much faster removal efficiency than the previous report of Lin et al. (2011). The results of the adsorption isotherm show that the data fitted well to the Langmuir isotherm model. The maximum adsorption of chromium ions composite nanofibers is 108 mgCr/gFeCl2. An attempted model prediction of the transient dynamics of adsorption-desorption elucidated the feasible kinetic analysis of Cr6+ from the PAN/FeCl2 composite nanofibers. This kinetic modeling can be used both for adsorption of heavy metals wastewater and for organic-adsorption and biosorption of diverse wastewaters. The PAN/FeCl2 composite nanofibers producted in this study exhibit high efficiency in Cr(VI) removal from wastewater, and may be used as a reference for future investigation. PMID- 26369158 TI - Highly Ordered Vertical Arrays of TiO2/ZnO Hybrid Nanowires: Synthesis and Electrochemical Characterization. AB - We report the fabrication of vertically aligned hierarchical arrays of TiO2/ZnO hybrid nanowires, consisting of ZnO nanowires grown directly from within the pores of TiO2 nanotubes, through a combination of electrochemical anodization and hydrothermal techniques. These novel nano-architectured hybrid nanowires with its unique properties show promise as high performance supercapacitor electrodes. The electrochemical behaviour of these hybrid nanowires has been studied using Cyclic voltammetry, Galvanostatic charge-discharge and Electrochemical impedance spectroscopy (EIS) measurements using 1.5 M tetraethylammoniumtetrafluoroborate in acetonitrile as the electrolyte. Excellent electrochemical performances with a maximum specific capacitance of 2.6 mF cm-2 at a current density of 10 uA cm-2, along with exceptional cyclic stability, have been obtained for TiO2/ZnO-1 h hybrid material. The obtained results demonstrate the possibility of fabricating new geometrical architectures of inorganic hybrid nanowires with well adhered interfaces for the development of hybrid energy devices. PMID- 26369159 TI - Analysis of Chameleonic Change of Red Cabbage Depending on Broad pH Range for Dye Sensitized Solar Cells. AB - Dye-sensitized solar cells (DSSCs) were assembled using natural dyes extracted from red cabbage as a sensitizer. In this work, we investigated the adsorption characteristics and the electrochemical behavior for harvesting sunlight and electron transfer in red cabbage DSSCs under different solvents and pH. For the red cabbage dye-sensitized electrode adsorbed at pH 3.5, the solar cell yields a short-circuit current density (Jsc) of 1.60 mA/cm2, a photovoltage (Vcc) of 0.46 V, and a fill factor of 0.55, corresponding to an energy conversion efficiency (eta) of 0.41%. PMID- 26369160 TI - Self-Assemblies of Acicular Hollow Fe/C Nanostructures. AB - Self-assemblies of acicular hollow Fe/C structures were synthesized using D glucose monohydrate and ferric chloride as precursors by a simple hydrothermal process followed by carbonization at 800 degrees C. The self-assembled structures with an overall diameter of 15~20 um composed of radially formed hollow needles from a central core with an average diameter of ca. 1 um and a length up to 10 um. The end of the needles was revealed to be a awl shape with a hollow structure formed during the self-assembly process and the subsequent heat treatment. The hollow structure was probably caused by the Kirkendall effect at 800 degrees C. The materials exhibit ferromagnetic characteristic with saturation magnetization (Ms), remanent magnetization (Mr), and coercivity (Hc) of 22.2 emu/g, 3 emu/g, and 151.22 Oe, respectively, with Ms much lower than that of Fe3O4. PMID- 26369161 TI - The Structural and Electronic Properties of CdS/ZnS Core-Shell Nanowires. AB - The structural and electronic properties of the CdS/ZnS core-shell nanowires (NWs) oriented along [001] direction have been investigated by means of the first principles calculation. It is found that CdS core suffers from the compressive strain in the CdS-core/ZnS-shell NWs, and ZnS core is stretched in the ZnS core/CdS-shell NWs. A thicker ZnS shell can improve the NWs' stability, and a thicker CdS shell would decrease their stability. For both CdS/ZnS core-shell NWs, the band gap decreases linearly with increasing the shell when the core size is fixed. However, when the diameter of NWs is fixed, CdS-core/ZnS-shell NWs with a thicker shell would have larger band gap. The results agree well with that of red-shift or blue-shift of the spectrum in experimental observations. The partial density of states indicates that the contribution to valence band maximum mainly comes from the S-3p state, and the contribution to conduction band minimum mainly comes from Cd-5s state for CdS-core/ZnS-shell NWs. Thus the electrons would be effectively confined in CdS core, and the holes tend to distribute over both the core and shell. It can be deduced that CdS-core/ZnS-shell NWs with a thicker shell may have larger mobility. PMID- 26369162 TI - Efficient Synthesis and Photosensitizer Performance of Nonplanar Organic Donor Acceptor Molecules. AB - Nonplanar organic donor-acceptor molecules bearing a carboxylic acid group were synthesized by the formal [2+2] cycloaddition-retroelectrocyclization reaction between aniline-substituted alkynes and tetracyanoethylene (TCNE) or 7,7,8,8 tetracyanoquinodimethane (TCNQ). This reaction offers an atom-economic one-step approach to donor-acceptor chromophores in satisfactory high yields. The resulting donor-acceptor molecules were characterized by conventional analytical techniques. In addition, the nonplanarity and intermolecular interactions were investigated by X-ray crystallography. The energy levels and intramolecular charge-transfer (CT), evaluated by UV-Vis-near IR spectroscopy and electrochemistry, suggested that there is a linear correlation between the optical and electrochemical band gaps. Based on these structural and electronic analyses, the photosensitizer performances of the donor-acceptor molecules in dye sensitized solar cells (DSSCs) were initially investigated using TiO2 or SnO2 electrodes. Although the power conversion efficiencies were limited, the incident photon-to-current-conversion efficiency (IPCE) spectra indicated a better photocurrent generation for the devices on SnO2 as compared to those on TiO2. PMID- 26369163 TI - High Stability Pentacene Transistors Using Polymeric Dielectric Surface Modifier. AB - 1,6-bis(trichlorosilyl)hexane (C6Cl), polystyrene (PS), and cross-linked polystyrene (CPS) were investigated as gate dielectric modified layers for high performance organic transistors. The influence of the surface energy, roughness and morphology on the charge transport of the organic thin-film transistors (OTFTs) was investigated. The surface energy and roughness both affect the grain size of the pentacene films which will control the charge carrier mobility of the devices. Pentacene thin-film transistors fabricated on the CPS modified dielectric layers exhibited charge carrier mobility as high as 1.11 cm2 V-1 s-1. The bias stress stability for the CPS devices shows that the drain current only decays 1% after 1530 s and the mobility never decreases until 13530 s. PMID- 26369164 TI - Synthesis, Characterization and Catalytic Properties of Attapulgite/CeO2 Nanocomposite Films for Decomposition of Rhodamine B. AB - ATP(attapulgite)/CeO2 nanocomposite films were prepared on the glass substrates via a sol-gel and dip-coating route. The ATP/CeO2 nanocomposite films were characterized by Powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), energy-dispersive spectrometry (EDS), transmission electron microscopy (TEM), atomic force microscopy (AFM) and fourier transform infrared spectroscopy (FT-IR). The results showed that the ATP/CeO2 nanocomposite films were free from cracks and the nanoparticles were attached onto the surface of attapulgite. The ATP/CeO2 nanocomposite films displayed excellent catalytic activity for decomposition of Rhodamine B. The COD (chemical oxygen demand) removal rate of rhodamine B using ATP/CeO2 nanocomposite films as catalyst reached as high as 94% when the weight ratio of ATP to CeO2 was 2:1. PMID- 26369165 TI - Comparative Study of Electrochemical Performance of SnO2 Anodes with Different Nanostructures for Lithium-Ion Batteries. AB - Powders composed of SnO2 nanostructures including microporous nanospheres, mesoporous nanospheres and nanosheets were synthesized by the direct hydrothermal hydrolyzation of SnCl4, hydrothermal hydrolyzation of SnCl4 using glucose as a soft template and precipitation of SnCl2 ? 2H20 using oxalic acid as a precipitant, respectively. The electrochemical performance of the three samples used as the anode of a lithium ion battery was determined using galvanostatic discharge/charge tests and electrochemical impedance spectroscopy. Among of them, the anode composed of microporous SnO2 nanospheres demonstrated outstanding initial discharge and charge capacities of 2480 and 1510 mAh g-1, respectively, with a coulombic efficiency of 60.9% at a current density of 78 mA g-1 (0.1 C). In addition, high initial discharge and charge capacities of 1398 mAh g-1 and 950 mAh g-1, respectively, with a coulombic efficiency of 67.95% were obtained even at a high current density of 550 mA g-1 (0.7 C). Moreover, a reversible capacity of 500 mAh g-1 with a coulombic efficiency of 99.95% was attained even after 50 discharging/charging cycles at 550 mA g-1 (0.7 C). This superior electrochemical performance of the SnO2 anodes can be attributed to the large specific surface area (172.7 m2 g-1), small crystal size (approximately 15 nm) and the interstitial microporous pores (<2 nm) of the particles, which favored lithium ion diffusion and insertion/desertion at the surface of SnO2 and decreased the polarization and the volume expansion of SnO2. Moreover, the resistance of the cell and Li+ diffusion coefficient were studied by electrochemical impedance spectroscopy. PMID- 26369166 TI - Modified Nano-Perovskite Catalysts for the Steam and CO2 Reforming of Methane. AB - This paper describes the synthesis and characterization of La0.8Sr0.2NiO3 nano perovskite type catalyst for steam-CO2 reforming (SCR) and CO2 reforming (DR) of methane. Effect of gelation agents such as PVA, EDTA and PAA on nano-perovskite structures was investigated. XRD, H2-TPR and FT-IR analysis were used to characterize the prepared catalysts. The catalytic reaction was performed in a fixed bed reactor system at 1 atm and 800 degrees C. The feed ratio of CH4:H2O:CO2 as reactants was adjusted according to the SCR and DR reactions. As a result, CH4 and CO2 conversions of PVA agent catalyst were higher than that of PAA and EDTA agent catalyst for DR reaction because the PVA agent catalyst had a well-established perovskite, a high absorption, a high reducibility. However, the PAA agent catalyst had a higher reactivity due to its high interaction of catalysts for SCR of methane due to its strong interaction of catalysts. PMID- 26369167 TI - Fabrication of Pd Micro-Membrane Supported on Nano-Porous Anodized Aluminum Oxide for Hydrogen Separation. AB - In the present study, nano-porous anodized aluminum oxide (AAO) was used as a support of the Pd membrane. The AAO fabrication process consists of an electrochemical polishing, first/second anodizing, barrier layer dissolving and pores widening. The Pd membrane was deposited on the AAO support using an electroless plating with ethylenediaminetetraacetic acid (EDTA) as a plating agent. The AAO had the regular pore structure with the maximum pore diameter of ~100 nm so it had a large opening area but a small free standing area. The 2 um thick Pd layer was obtained by the electroless plating for 3 hours. The Pd layer thickness increased with increasing the plating time. However, the thickness was limited to ~5 um in maximum. The H2 permeation flux was 0.454 mol/m2-s when the pressure difference of 66.36 kPa0.5 was applied at the Pd membrane under 400 degrees C. PMID- 26369168 TI - Combination of Surface Initiated Reversible Addition Fragmentation Chain Transfer Polymerization, Thiol-Ene Click Chemistry and Coordination Chemistry for the Fabrication of a Novel Photoluminescent Hydroxyapatite Nanohybrids. AB - Hydroxyapatite nanocrystals (HAPs) were encapsulated by poly(allyl methacrylate) (PAMA) employing controlled surface-initiated reversible addition-fragmentation chain transfer polymerization of allyl methacrylate to give HAP-PAMA nanohybrids. The subsequent thiol-ene coupling of nanohybrids with 2-mercaptosuccinic acid resulted in HAP-PAMA-COOH possessing multicarboxyl functionality. The coordination of the nanohybrids with Tb3+ ions in the presence of 1,10 phenanthroline (Phen) afforded photoluminescent Tb3+ tagged HAPs-PAMA nanohybrid complexes (HAP-PAMA-Tb3+-Phen). The structure, morphology, and fluorescence properties of the Tb3+ coordinated nanohybrid complexes were investigated by respective physical and spectral studies. PMID- 26369169 TI - Effects of Oxide Layer on the Bonding Strength of Ni-Cr Alloys with Porcelain Ceramics. AB - The metal-ceramic crown restoration was the most actively used at esthetic restoration for its convenience of forming. Due to constant rise of gold price, non-precious metal such as Ni-Cr alloy have been widely used as metal-ceramic restorations. For easy casting and lower melting point Be was added as minor component to Ni-Cr for a long time, but the use of Be was regulated to deteriorate to human lung. In this study, Ni-Cr specimens containing Be (T-3, Ticonium, USA) and non-Be (Bellabond Plus, BEGO, Germany) were fabricated and by heat treatments at 800-1050 0C oxide layer was formed for subsequent bonding to porcelain ceramics. By heat treatment of the non-Be specimens at high temperature more thick oxide layer was formed and showed lower bonding strength due to the debonding at oxide layers. But in the Be-containing specimens debonding was occurred at porcelain layer so that they showed higher bonding strength. So by heat treatment of non-Be specimens at vacuum condition rather thinner oxide film could be formed so that showed higher coupling strength due to the debonding at porcelain layers than oxide layers. PMID- 26369170 TI - Characterization of Fly Ash Modified with Vinyltriethoxysilane. AB - Here we report on the modification of fly ash (FA) with vinyltriethoxysilane (VTES) in order to enhance the dispersibility and avoid the agglomeration. FA was treated with nitric acid before the modification with VTES. The structure of fly ash particles before and after the modification was characterized by several sophisticated techniques including Fourier transform infra-red spectrum (FT-IR), thermogravimetric analysis (TGA), field emission scanning electron microscopy (FE SEM) and size distribution analysis. The obtained results show that the VTES was grafted successfully onto the surface of FA, which significantly changes the surface properties of FA. It was also found that the thermal stability of modified FA (MFA) is much higher than that of the FA treated only with nitric acid. The size of the FA particles can also be controlled from 0.2 to 1.5 um with increasing the loading of VTES on the surface of FA from 1 to 2 wt.%, revealing highly mono-distribution and low agglomeration. However, the agglomeration of the particles is observed when the content of VTES on the surface of FA exceeds 2 wt.%. PMID- 26369171 TI - Comparative Investigation on the Photocatalytic Degradation of 2,4,6 Trichlorophenol Using Pure and M-Doped (M = Ba, Ce, Mg) ZnO Spherical Nanoparticles. AB - Pure and M-doped (Ba, Ce, Mg) ZnO spherical nanoparticles are synthesized by a simple low temperature co-precipitation method, and were characterized by X-ray diffraction (XRD), high resolution scanning electron microscopy (HR-SEM), and high resolution transmission electron microscopy (HR-TEM). The XRD results showed the formation of single phase ZnO with wurtzite crystal structure and the electron microscopic studies supported the validity for the formation of pure and M-doped (Ba, Ce, Mg) ZnO spherical nanoparticles. Photocatalytic degradation (PCD) of 2,4,6-trichlorophenol, a potent endocrine disrupting chemical in aqueous medium was investigated by both pure and M-doped (Ba, Ce, Mg) ZnO spherical nanoparticles under UV-light irradiation. The influence of the metal dopants on the structure and photocatalytic (PC) activity of ZnO was investigated systematically. Furthermore, the effect of different parameters such as 2,4,6 trichlorophenol concentration, photocatalyst amount, pH and dopant wt% on the resulting PC activity was investigated. The kinetics of the photocatalytic degradation of 2,4,6-trichlorophenol was found to follow the pseudo-first order reaction, and it was established that Ba-doped ZnO is photocatalytically more active than the other photocatalysts. PMID- 26369172 TI - Bio-inspired Fabrication of Complex Hierarchical Structure in Silicon. AB - In this paper, we developed a top-down method to fabricate complex three dimensional silicon structure, which was inspired by the hierarchical micro/nanostructure of the Morpho butterfly scales. The fabrication procedure includes photolithography, metal masking, and both dry and wet etching techniques. First, microscale photoresist grating pattern was formed on the silicon (111) wafer. Trenches with controllable rippled structures on the sidewalls were etched by inductively coupled plasma reactive ion etching Bosch process. Then, Cr film was angled deposited on the bottom of the ripples by electron beam evaporation, followed by anisotropic wet etching of the silicon. The simple fabrication method results in large scale hierarchical structure on a silicon wafer. The fabricated Si structure has multiple layers with uniform thickness of hundreds nanometers. We conducted both light reflection and heat transfer experiments on this structure. They exhibited excellent antireflection performance for polarized ultraviolet, visible and near infrared wavelengths. And the heat flux of the structure was significantly enhanced. As such, we believe that these bio-inspired hierarchical silicon structure will have promising applications in photovoltaics, sensor technology and photonic crystal devices. PMID- 26369173 TI - Synthesis, Characterization and Adsorption Properties of Magnetic gamma-Fe2O3/C Nanocomposite. AB - gamma-Fe2O3/C nanocomposite was prepared through a convenient method by which one pot synthesized Fe3O4/Starch was oxidized and carbonized by calcining at 250 degrees C. The gamma-Fe2O3/C displayed strong magnetism and could adsorb organic molecules from aqueous solution effectively, thus it showed promising application in the dislodgement of organic pollutants in sewage. Adsorption isotherms and kinetics of methylene blue (MB) onto gamma-Fe2O3/C were studied in a batch system. The adsorption process reached equilibrium in about 15 min, and the maximum adsorption capacity of MB was found to be 64.9 mg g-1 at 303 K. Adsorption isotherms were well fitted to Langmuir model and the adsorption kinetics could be described by the pseudo-second order kinetic equation. The findings of the present work highlight a new facile method to fabricate magnetic carbon-based composites and the obtained gamma-Fe2O3/C with excellent magnetic property and adsorption performance hold great promise for practical application in water treatment. PMID- 26369174 TI - Combined Effect of Carrier Localization and Polarity in InxGa1-xN/GaN Quantum Wells. AB - The influence of carrier localization and polarization-induced electric fields on the spectral variation of photoluminescence was comparatively studied in polar and semipolar InxGa1-x N/GaN strained quantum wells embedded in p-i-n diodes. Two representative structures with x = 0.16 for polar (0001) diodes and potential fluctuations for semipolar diodes grown along (1122) direction have been investigated with a reverse bias up to -4 V. From the s-shaped spectral shift as a function of temperature, the existence of single and triple localization traps was confirmed in polar and semipolar diodes. Within our bias range, we observed the monotonic blueshift with reverse bias in the polar sample, indicating that the carriers are laterally localized and thus influenced by the vertical piezoelectric fields. In clear contrast, the semipolar sample showed the blueshift of localized states only at low temperatures, while the deepest localization features were found at the highest available temperatures, overriding the influence of thermal activation and polarization fields. PMID- 26369175 TI - Statistical Analysis of Electrical Properties of Octanemonothiol versus Octanedithol in PEDOT:PSS-Electrode Molecular Junctions. AB - We fabricated a large number of octanemonothiol (C8) and octanedithol (DC8) molecular electronic devices with PEDOT: PSS (3,4-ethylenedioxythiophene) interlayer and performed a statistical analysis on the electronic properties of these devices. From the analysis, we obtained the Gaussian plot of histograms of Log10 (current density (J)) and several statistical estimates such as arithmetic mean, median, Gaussian mean, arithmetic standard deviation, adjusted absolute median deviation, and Gaussian standard deviation. We determined the current density-voltage (J-V) characteristics from the statistically representative data for C8 and DC8 devices and found that the conductivity of C8 is higher than that of DC8 by a factor of ~10. The difference of the conductivity of C8 and DC8 devices is attributed to the difference of the contact properties between the C8 and DC8 PEDOT:PSS-interlayer molecular junctions. PMID- 26369176 TI - Effects of Electron Beam Irradiation on the Electrospinning of Polyacrylonitrile. AB - Electron beam (e-beam) irradiation of polyacrylonitrile (PAN) was performed to investigate the effects of radiation on the electrospinning process. For this study, polyacrylonitrile powder was subjected to e-beam irradiation with different doses of up to 100 kGy under an N2 atmosphere. Polymer solutions were prepared by dissolving PAN in N,N-dimethyl-formamide (DMF) at a 1:9 ratio by weight. The prepared PAN/DMF solutions showed different colors with different e beam doses. The resulting structures in solutions contained conjugated C=N bonds, which caused the observed color formation. In addition, the conductivity of the PAN/DMF solution increased with an increase in e-beam irradiation dose. In the DSC spectra of electrospun PAN fibers, the peak temperature of the exothermic reactions was observed to decrease with an increase in the e-beam irradiation strength. PMID- 26369177 TI - Surface Modification of Zirconia Substrate by Calcium Phosphate Particles Using Sol-Gel Method. AB - Surface modification with a biphasic composition of hydroxyapatite (HA) and tricalcium phosphate (TCP) was performed on a zirconia substrate using a sol-gel method. An initial calcium phosphate sol was prepared by mixing a solution of Ca(NO3)2 . 4H20 and (C2H5O)3P(O), while both porous and dense zirconia were used as substrates. The sol-gel coating was performed using a spin coater. The coated porous zirconia substrate was re-sintered at 1350 degrees C 2 h, while coated dense zirconia substrate was heat-treated at 750 degrees C 1 h. The microstructure of the resultant HA/TCP coatings was found to be dependent on the type of zirconia substrate used. With porous zirconia as a starting substrate, numerous isolated calcium phosphate particles (TCP and HA) were uniformly dispersed on the surface, and the particle size and covered area were dependent on the viscosity of the calcium phosphate sol. Conversely, when dense zirconia was used as a starting substrate, a thick film of nano-sized HA particles was obtained after heat treatment, however, substantial agglomeration and cracking was also observed. PMID- 26369178 TI - Studies on the Characteristics of Vertical Organic Transistor with Nano Patterned Gate Using Block Copolymer. AB - In this study, we fabricated and studied the device characteristics of vertical organic transistors consisting of nano-patterned gates constructed from the self assembly of block copolymer. The size of the gate opening made by the new method was 30~40 nm. The device was compared with those which had gate openings of 200 nm. These lager devices were constructed from monodispersed colloidal polystyrene spheres. The device which used block copolymer showed significant improvements in its on-off ratio. We also fabricated transistors with tungsten oxide buffer layer to increase the on current of the device. The devices were analyzed based on their current-voltage charac- teristics, impedance spectroscopy, atomic force microscope (AFM) images and scanning electron microscope (SEM) images. PMID- 26369179 TI - Influence of Glyoxal on Preparation of Poly(Vinyl Alcohol)/Poly(Acrylic Acid) Blend Film. AB - The preparation of a poly(vinyl alcohol)/poly(acrylic acid)/glyoxal film (PVA = poly(vinyl alcohol); PAA = poly(acrylic acid)) with high tensile strength and hydrophobic properties by using the crosslinking reaction for OH group removal is reported herein. PAA was selected as a crosslinking agent because the functional carboxyl group in each monomer unit facilitates reaction with PVA. The OH groups on unreacted PVA were removed by the addition of glyoxal to the PVA/PAA solution. The chemical properties of the PVA/PAA films were investigated using Fourier transformation infrared spectroscopy and the thermal properties of the PVA/PAA/glyoxal films were investigated by means of differential scanning calorimetry and thermogravimetric analysis. A tensile strength of 48.6 N/mm2 was achieved at a PVA/PAA ratio of 85/15 for the PVA/PAA film. The tensile strength of the cross-linked PVA/PAA/glyoxal film (10 wt% glyoxal) was increased by 55% relative to the pure PVA/PAA (85/15) film. The degree of swelling (DS) and solubility (S) of the 10 wt% (PVA/PAA = 85/15, wt%) film added 10 wt% glyoxal were 1.54 and 0.6, respectively. PMID- 26369180 TI - Ni/MgO-MgAl2O4 Catalysts with Bimodal Pore Structure for Steam-CO2-Reforming of Methane. AB - The bead type MgO-MgAl2O4 catalyst supports with bimodal pore structures were fabricated via an extrusion molding of gels derived from the precursor mixture of mesoporous MgO particles and aluminum magnesium hydroxide, followed by heat treatment. To investigate the effect of macro pore structures on the catalytic activity of the Ni/MgO-MgAl2O4 catalysts in the steam and carbon dioxide reforming of methane (SCR), two kinds of the catalysts with largely different macro pore volumes and sizes but nearly the same meso pore volume and size were compared. The bimodal catalyst with a large macro pore size and volume exhibited a highly enhanced CO2 conversion from 22.3 to 37.1% but a slightly reduced CH4 conversion from 95.3 to 92.1% at the same feed ratio. The SCR results show that the large macro pores can lead to a highly enhanced mass transfer rate of CO2 absorption into the pore channels of the magnesium alumina spinel. PMID- 26369181 TI - Photocurrent Enhancement of P3HT:PCBM Organic Solar Cell with Cylindrical Ag-NPs by EBM. AB - The power conversion efficiency (PCE) of PEDOT: PSS/P3HT:PCBM organic solar cells(SCs) with Ag nanoparticles (NPs) on ITO is studied, and the optical absorption of the SCs with a cylindrical Ag-NPs model is investigated. The fabricated device structure is simulated with a finite difference time domain (FDTD) method. This cylindrical Ag-NPs model is able to explain the photocurrent enhancement by the localized surface plasmon resonance (LSPR) modes, and to provide a further understanding of Ag-NPs shape parameters which play an important role to determine the broadband absorption phenomena in plasmonic organic solar cells. Compared with the SCs without Ag-NPs, an increase in the PCE of the plasmonic solar cell was accurately identified. The photocurrent-voltage characteristic of the examined solar cells reveals higher efficiency of 2.75% compared with the reference cells which show 1.67%. PMID- 26369182 TI - Fabrication N, F, and N/F-Doped TiO2 Photoelectrodes for Dye-Sensitized Solar Cells. AB - In this study, pure TiO2, N-doped TiO2, F-doped TiO2, and N/F-doped TiO2 particles were successfully synthesized through the hydrolysis of TiCl4 in the presence of ammonia water and NH4F, respectively. The introduction of doping materials did not affect the crystalline structure. No absorption peak for pure TiO2 was observed above the wavelength of 400 nm. However, the N-doped TiO2 and N/F-doped TiO2 powders exhibited a new absorption peak in the visible light region between 400 and 530 nm. The Jsc value of DSSCs based on the N/F-doped TiO2 electrode was increased by 10% compared to DSSCs using a pure TiO2 electrode, and the energy conversion efficiency was increased by 12%. PMID- 26369183 TI - A Mask-Free Passivation Process for Low Noise Nanopore Devices. AB - Solid-state nanopores have been studied widely for the label-free analysis of single biomolecules. The translocation of charged biomolecules through a solid state nanopore is driven by the applied voltage across a thin membrane. The ionic current changes in response to the translocation of DNA through the nanopore. Solid-state nanopores have many advantages over biological nanopores, such as alpha-hemolysin and MspA, but the high DNA translocation velocity and the inherent noise in solid-state nanopores have hindered its applications to more precise measurements, such as DNA sequencing. This paper reports a simple and reproducible way of passivating the surface of a nanopore device using an insulating layer, photodefinable PDMS (P-PDMS), to reduce noise and enhance the accuracy of the electrical measurements. This new approach does not require a separate photo-mask or sophisticated micro-alignment equipment to pattern the insulating layer. The pit structure on the back side of the support chip serves as a mask, enabling mask-free photolithography, and the insulating layer only on top of the free-standing silicon nitride membrane can be irradiated selectively by UV and removed by subsequent development in toluene. The resulting nanopore device with a small free standing silicon nitride membrane surrounded by a thick insulating layer showed improved noise characteristics. The root-mean-square noise of the ionic current was reduced to 3.8 pA from 90.8 pA by the formation of a micron-thick insulating layer. The overall performance of the nanopores with an insulating layer was improved significantly when tested with the double-stranded DNA (lambda-DNA). PMID- 26369184 TI - Mechano-Thermal Synthesis and Characterization of BaMnO3 Nano-Needles. AB - Various BaMnO3 samples were prepared by planetary ball milling technique by varying the milling time from 1 to 20 h at a speed of 350 rpm, and all the milled powders were subsequently annealed at 1000 degrees C for 16 h in order to improve the phase formation and purity. While the ball milled powders are amorphous in nature, the annealed materials reveal nanocrystalline hexagonal perovskite structure with space group, P6(3)/mmc (194). The 15 h ball milled and subsequently annealed material shows lattice parameters, a = 0.5704(5) and c = 0.4801(6) nm with lowest average crystalline size of ~18 nm. It is found that, as the milling time increases (from 1 h to 15 h) the average crystalline size decreases slightly from 25.7 nm to 18.1 nm. The nano rod/needle shaped particles with the size of ~97 nm are observed through SEM images for the BaMnO3 phase. Interestingly, the present BaMnO3 nanopowder reveals photo-luminescent property under the excitation wavelengths of 270 and 350 nm. The nanocrystalline BaMnO3 powder exhibits higher reflectance, which finds application in NIR reflective pigments. PMID- 26369185 TI - Nanomolding the Surface of Polymer Films. AB - Slight changes in the experimental procedures of the micro contact printing (ACP) technique are introduced here, which allow for using polymers soluble in distinct solvents to fabricate submicrometric 2D periodic structures. Highly reproducible secondary and tertiary poly(dimethylsiloxane) (PDMS) molds could be produced, as demonstrated in atomic force microscopy images and light diffraction experiments. The replication of tertiary molds with no residues of PDMS demonstrates the feasibility of large-scale production with distinct polymers. The plane wave propagation along the tertiary poly(3,4-ethylenedioxythiophene) with poly(hydrogen 4-styrene sulfonate) molds was simulated with a finite-difference time-domain algorithm. A strong wave propagation was observed in the region containing the structures acting as a wave guide, in agreement with the results from the experimental absorption measurements. Furthermore, we show that the optical properties of the molds and their roughness can be tuned by choosing the polymers (including biopolymers) for printing pillars and tracks, thus bringing new possibilities for nanomolding of polymer surfaces for photonics, organic electronics and bioelectronics. PMID- 26369186 TI - In-Situ Spectroscopic Analyses of the Dye Uptake on ZnO and TiO2 Photoanodes for Dye-Sensitized Solar Cells. AB - UV-Vis spectroscopic measurements have been performed on Dye-Sensitized Solar Cell (DSSC) photoanodes at different dye impregnation times ranging from few minutes to 24 hours. In addition to the traditional absorbance experiments, based on diffuse and specular reflectance of dye impregnated thin films and on the desorption of dye molecules from the photoanodes by means of a basic solution, an alternative in-situ solution depletion measurement, which enables fast and continuous evaluation of dye uptake, has been employed. Two different nanostructured semiconducting oxide films (mesoporous TiO2 and sponge-like ZnO) and two different dyes, the traditional Ruthenizer 535-bisTBA (N719) and a newly introduced metal-free organic dye based on a hemi-squaraine molecule (CT1), have been analyzed. DSSCs have been fabricated with the dye-impregnated photoanodes using a customized microfluidic architecture. The dye adsorption results are discussed and correlated to the obtained DSSC electrical performances such as photovoltaic conversion efficiencies and Incident Photon-to-electron Conversion Efficiency (IPCE) spectra. It is shown that simple UV-Vis measurements can give useful insights on the dye adsorption mechanisms and on the evaluation of the optimal impregnation times. PMID- 26369187 TI - Identification of Domain Boundary Defects in Crystalline Self-Assembled Monolayers. AB - One of the major challenges to the fabrication of functionalized templates using self-assembled monolayers (SAMs) is the characterization of nanoscale defects, particularly SAM domain boundaries (DBs). In this study, an etchant was used to chemically amplify the DBs in a SAM by forming microscale pits in the underlying SiO2 layer. This approach revealed that the naturally occurring DBs acted as structural defects in the SAMs. The DB structures were characterized by systematically varying the octadecyltrichlorosilane (ODTS) monolayer domain size from the nanoscale to the microscale by varying the preparation temperature. These approaches showed that the SAM DBs, which were visualized as having round- and line-shaped nanoscale structures, provided potentially chemical and mechanical surface defect sites. Our principal findings open up exciting new possibilities for understanding the structural defects in SAMs on the molecular level and suggest an approach for optimizing the conditions used to generate defect-free SAM templates. PMID- 26369188 TI - Self-Assembly of Ag Nanoparticles Induced by Centrifuging and Broken by Silanization. AB - A novel method was developed to assemble Ag nanoparticles (NPs) into chain-like structures. The assembly of the NPs was created by suspending in an ethanol and water solution as well as centrifuging at a high speed (a force of more than 29 Kg for the NPs with an average diameter of 18 nm). The composition of solvents and centrifuged speeds of samples play important roles for the formation of regular assemblies. The number of Ag NPs in the chain-like assemblies was adjusted by changing centrifuging forces. The assemblies of the NPs were fixed by a SiO2 coating through a St6ber synthesis. In addition, the assemblies were broken through a silanization process because of partially hydrolyzed tetraethyl orthosilicate molecules adsorbed on the surface of Ag NPs to form a SiO2 layer opposite aggregation. A slow silanization process made Ag NPs monodispersed in solutions, in which Ag/SiO2 core/shell NPs were created. PMID- 26369189 TI - Preparation and Optical Waveguiding Property of Single-Crystal Organic NPB Microsheets. AB - 2D microstructures of N,N'-diphenyl-N,N'-bis(1-naphthyl)-1,1'-biphenyl-4,4'-di amine (NPB) have been prepared by a facile solution method and fully characterized. The as-prepared NPB microsheets have well-defined shapes and very smooth surfaces, and are ideal building blocks for 2D optical waveguides. The results indicate that the optic losses within NPB microsheets are closely related to the direction of propagation, and the shape of microsheets can change the direction of waveguiding light. Such 2D optical waveguides may have potential applications in future miniaturized light-based circuits serve as interconnectors different from 1 D optical waveguides. PMID- 26369190 TI - The Characteristics of an Antibacterial TiAgN Thin Film Coated by Physical Vapor Deposition Technique. AB - In this work, we found the characteristics of an antibacterial TiAgN thin film coated on the pure titanium specimen via the physical vapor deposition process (PVD). TiAgN thin films were coated using TiAg alloy targets by arc ion plating method. Changing the process parameters, the surface analysis of TiAgN thin film was observed by FE-SEM and the force of adhesion was measured with Scratch Tester. The proliferation of human gingival fibroblast (HGF) cells was examined by XTT test assay and the antibacterial properties were investigated by culturing Streptococus Mutans (KCTC 3065) using paper disk techniques. At the result of experiment, cytotoxic effects were not found and the antibacterial effects against Streptococus Mutans were appeared over 5 wt% TiAgN specimens. PMID- 26369191 TI - Polarized Terahertz Waves Emitted from In0.2Ga0.8As Nanowires. AB - We investigate the polarizability of terahertz (THz) waves emitted from undoped In0.2Ga0.8As nanowires (NWs). THz emission amplitude shows strong enhancement in vertically aligned NWs compared to less-aligned NWs. In particular, polarized THz waves are clearly demonstrated in aligned NWs via a drastic variation of amplitudes as a function of the axis angle in polarization-sensitive photoconductive antenna. In addition, phase reversal between aligned and less aligned NWs substantiates the geometrical dependence of electronic diffusion in generating the transient THz electric fields. PMID- 26369192 TI - Preparation and Study on Nickel Oxide Reduction of Polyacrylonitrile-Based Carbon Nanofibers by Thermal Treatment. AB - Carbon materials containing magnetic nanopowder have been attractive in technological applications such as electrochemical capacitors and electromagnetic wave shielding. In this study, polyacrylonitrile (PAN) fibers containing nickel nanoparticles were prepared using an electrospinning method and thermal stabilization. The reduction of nickel oxide was investigated under a nitrogen atmosphere within a temperature range of 600 to 1,000 degrees C. Carbon nanofibers containing nickel nanoparticles were characterized by FE-SEM, EDS, XRD, TGA, and VSM. It was found that nickel nanoparticles were formed by a NiO reduction in PAN as a function of the thermal treatment. These results led to an increase in the coercivity of nanofibers and a decrease in the remanence magnetization. PMID- 26369193 TI - Influence of Starting Powders on Hydroxyapatite Coatings Fabricated by Room Temperature Spraying Method. AB - Three types of raw materials were used for the fabrication of hydroxyapatite coatings by using the room temperature spraying method and their influence on the microstructure and in vitro characteristics were investigated. Starting hydroxyapatite powders for coatings on titanium substrate were prepared by a heat treatment at 1100 degrees C for 2 h of bovine bone, bone ash, and commercial hydroxyapatite powders. The phase compositions and Ca/P ratios of the three hydroxyapatite coatings were similar to those of the raw materials without decomposition or formation of a new phase. All hydroxyapatite coatings showed a honeycomb structure, but their surface microstructures revealed different features in regards to surface morphology and roughness, based on the staring materials. All coatings consisted of nano-sized grains and had dense microstructure. Inferred from in vitro experiments in pure water, all coatings have a good dissolution-resistance and biostability in water. PMID- 26369195 TI - Morphological Control of Bi2Te3 Nanotubes and Their Thermoelectric Properties. AB - Highly uniform Bi2Te3 nanotubes with various morphologies are synthesized via a solution process using Te nanowires as a sacrificial template. The morphology of Bi2Te3 nanotubes can be controlled by varying the solvent system. The reaction between Bi and Te in triethylene glycol (TEG) produces Bi2Te3 nanotubes with plate-like surface morphology, whereas rough surface morphology of the Bi2Te3 nanotubes is obtained by the reaction in ethylene glycol (EG). The crystal structures and morphologies of nanotubes are investigated X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM). The effect of solvent on the evolution of morphology of the Bi2Te3 nanotubes is investigated. The effect of surface morphology on the thermoelectric properties is discussed. PMID- 26369194 TI - Fabrication and Microstructure of Hydroxyapatite Coatings on Zirconia by Room Temperature Spray Process. AB - Hydroxyapatite coatings were fabricated on zirconia substrates by a room temperature spray process and were investigated with regards to their microstructure, composition and dissolution in water. An initial hydroxyapatite powder was prepared by heat treatment of bovine-bone derived powder at 1100 degrees C for 2 h, while dense zirconia substrates were fabricated by pressing 3Y TZP powder and sintering it at 1350 degrees C for 2 h. Room temperature spray coating was performed using a slit nozzle in a low pressure-chamber with a controlled coating time. The phase composition of the resultant hydroxyapatite coatings was similar to that of the starting powder, however, the grain size of the hydroxyapatite particles was reduced to about 100 nm due to their formation by particle impaction and fracture. All areas of the coating had a similar morphology, consisting of reticulated structure with a high surface roughness. The hydroxyapatite coating layer exhibited biostability in a stimulated body fluid, with no severe dissolution being observed during in vitro experimentation. PMID- 26369197 TI - Enhanced Electrochemical Properties of LiMnPO4/C by Glucose-Assisted Polyol Synthesis. AB - Carbon-coated nano-sized LiMnPO4/C particles are synthesized by polyol method using low-cost glucose as the carbon source. The X-ray diffraction patterns of the synthesized samples are well indexed to the orthorhombic olivine-LiMnPO4 structure. The morphology studies using FE-SEM and HR-TEM images clearly illustrate thin layered carbon coatings on LiMnPO4 particles of sizes ranging between 50~100 nm. The LiMnPO4/C particles delivers an initial discharge capacity of 151 mA h g-1 at a current density of 1.6 mA g-1 in the voltage range of 2.5 4.3 V with impressive capacity retentions. PMID- 26369196 TI - O2/Ar Plasma Treatment for Enhancing the Biocompatibility of Hydroxyapatite Nanopowder and Polycaprolactone Composite Film. AB - In this study we performed O2/Ar plasma treatment to remove the polycaprolactone on hydroxyapatite nanopowder and polycaprolactone (HAp-NP/PCL) composite film. After plasma ashing, the HAp-NP was exposed on the composite film. The 25 wt% HAp NP/PCL treated with plasma showed the hydrophilic surface property with reducing the aging effect. The MTT and ALP results indicated that the plasma etching increased the biocompatibility of HAp-NP/PCL composite film. The present simple plasma etching technique can be applicable in a development of biomaterials. PMID- 26369198 TI - Facile Preparation of Bifunctional Monodisperse Nanospheres with Tunable Size and Luminescence. AB - Nanotechnology has found wide use in biomedical applications and the food and bioprocessing industry. In this light, we demonstrate a facile strategy to prepare bifunctional monodisperse silica nanospheres encapsulating chitosan coated magnetic nanoparticles and CdTe quantum dots. The size of these composite spheres can be adjusted from 90 nm to 500 nm by varying the concentration of ammonia, water, tetraethyl orthosilicate, and the ratio of the chitosan-coated magnetic nanoparticles and CdTe quantum dots. The composite spheres are characterized using scanning electron microscope analyses, transmission electron microscope analyses, energy-dispersed spectrum studies, Malvern Zetasizer, vibrating sample magnetometer, and fluorescence microscopy. The spheres exhibit good monodispersion and favorable superparamagnetic and fluorescent properties. The luminescence of the spheres can be varied by using different types of coated quantum dots. Such composite spheres with tunable characteristics allow for external manipulation of research systems by magnetic fields together with the real-time fluorescent monitoring of multiple samples. The abovementioned properties can potentially be exploited for application in the biomedical and biosensing fields. PMID- 26369199 TI - Convenient Route to Well-Dispersed Cu2O Nanospheres and Their Use as Photocatalysts. AB - A simple and facile method was developed to synthesize well-dispersed cuprous oxide nanospheres with uniform morphology and the size in the range of 400-600 nm. Cuprous oxide nanospheres were obtained through the chemical reduction of copper acetate by fructose in the presence of ethylene glycol and de-ionized water. X-ray powder diffraction (XRD), Energy dispersive X-ray spectroscopy (EDX), scanning electron microscopy (SEM), UV-Vis spectroscopy (UV-Vis) and transmission electron microscopy (TEM) as well as high-resolution transmission electron microscopy (HRTEM) were used to characterize the obtained nanoparticles. The influence of time, temperature and the solvent on the formation of cuprous oxide was investigated. The growth process of cuprous oxide was analyzed and the mechanism of crystal growth was proposed. The photocatalytic activity of degradation of methyl orange (MO) under visible light irradiation was also investigated. It was found that the product of cuprous oxide had efficient catalytic for degradation MO. PMID- 26369200 TI - Effect of Heat-Treatment and Composition on Structure and Luminescence Properties of Spinel-Type Solid Solution Nanocrystals. AB - The compositional dependence of the structure and properties of spinel-type solid solutions, Zn(A,Ga)2O4 was investigated by comparison with samples hydrothermally prepared and those after heat treatment at 1000 degrees C in air. Nanocrystalline spinel-type solid solutions in the whole composition range in the ZnAl2O4-ZnGa2O4 system were directly formed from the aqueous precursor solutions of ZnSO4, Al(NO3)3 and Ga(NO3)3 under hydrothermal conditions at 180 degrees C for 5 h in the presence of tetramethylammonium hydroxide. The incorporation of aluminum into the lattice, Zn(AlxGa1-x)2O4, resulted in lower crystallinity of the spinel. The relationship between the lattice parameter of as-prepared samples and the Al atomic ratio in the spinel composition was slightly apart from the ideal linear relationship that was obtained in the samples after heat treatment at 1000 degrees C. The optical band gap of both as-prepared solid solutions and those heat treated linearly increased from 4.1~4.2 to 5.25 eV by the incorporation of aluminum ion into the lattice, Zn(AlxGa1-x)2O4. Two main broad band emission spectra centered at around 360 and 430 nm in the range of 300-600 nm were observed in the spinel solid solutions under excitation at 270 nm, thought their broad-band emission spectra and their peak wavelengths subtly changed depending on the composition and heat treatment. PMID- 26369201 TI - Enhanced Electrochemical Oxidation of p-Nitrophenol Using Single-Walled Carbon Nanotubes/Silver Nanowires Hybrids Modified Electrodes. AB - The electrochemical oxidation of p-nitrophenol (p-Np) has been studied on glassy carbon electrode modified with the single-walled carbon nanotubes/silver nanowires hybrids (SWNTs-Ag) by using cyclic and differential pulse voltammetry. p-Np is irreversibly oxidized at +0.88 V (vs. the Ag/AgCl) in PBS solutions of pH 7.4. The modified electrodes display the detection sensitivity of 0.0212 uA/uM with an unusually wide linear response of 5-1700 uM (R2 = 0.998) and the detection limit of 1 uM. The current response of SWNTs-Ag modified electrode to p Np is better than that of SWNTs or Ag nanowires modified electrode under the same concentration. Combining the adsorption ability of SWNTs and the conductivity of SWNTs and Ag nanowires, the detection performance of SWNTs-Ag modified electrode to p-Np was greatly improved. PMID- 26369202 TI - Dielectric Relaxation of NiFe2O4/Gd2O3 Core-Shell Nanoparticles. AB - Gd2O3 encapsulated NiFe2O4 core-shell nano-particles (CSNPs) have been synthesized by chemical route. The phase formation of the materials is confirmed by X-ray diffraction analysis. The average particle size is found to be 60 nm by transmission electron microscope. The band gap of NiFe2O4/Gd2O3 CSNPs is obtained by UV-visible absorption spectroscopy. The observed band gap of 4.38 eV lies in between the individual band gap of Gd2O3 and NiFe2O4. The frequency-dependent dielectric relaxation of the material is investigated in the temperature range from 303 K to 543 K. The temperature dependent relaxation times are found to obey Arrhenius law having activation energy of 0.3 eV. The Nyquist plots of impedance data are analyzed by the RC equivalent circuit having a constant phase element. The dielectric relaxation is modelled by Havriliak-Negami technique in the electric modulus formalism. The frequency dependent conductivity spectra follow the double power law. PMID- 26369203 TI - Controllable Growth of Superfine Silver Nanowires by Self-Seeding Polyol Process. AB - Superfine silver nanowires (Ag NWs) with diameter of 40~50 nm and length of 5~10 um have been synthesized by the self-seeding polyol reduction process using silver nitrate as the silver source, polyvinyl pyrrolidone (PVP) as the structural directing agent, ethylene glycol (EG) as the reducing agent and AgBr as the mediator. The influence of different factors on the growth of Ag NWs was studied. The morphology and crystalline phase of Ag NWs were characterized by the field emission scanning electron microscopy (SEM) and X-ray diffraction (XRD) respectively. The results indicate that the introduction of potassium bromide (KBr) is helpful for growth of Ag NWs with a high aspect ratio, as AgBr colloids formed in the initial stage and the dissociation reaction of AgBr colloids would largely influence the delivering rate of Ag+ ions, which controls the nucleation and growth of the Ag NWs. Finally, the possible growth mechanism of Ag NWs was discussed. PMID- 26369204 TI - Flattened Multiwalled Carbon Nanotube with Multi-Layered Structure. AB - Fabrication of novel nanostructures based on carbon nanotubes has been a focus of recent interest since they are expected to inherit excellent properties of carbon nanotube. To find new nanotube-based nanostructures, it is important to find a new growth mode or process. This paper reports the formation of a multiwalled carbon nanotube that has bi-layered structure and is partly flattened. Transmission electron microscopy observations suggest that the outer multiwalled layer was formed first from a Fe catalyst nanoparticle, and was partly flattened during the growth. Then the catalyst nanoparticle worked again to form the inner multiwalled tube moving inside the outer tube and became flattened at the same position of the outer tube. It is likely that the inner growth gave an expansion stress against the flattened outer tube; nevertheless, the flattened part of the outer tube remained. This observation evidences that the flattening of the nanotube occurred simultaneously during the growth and was stabilized by structural defect. PMID- 26369205 TI - High Internal Gain Axial SiOx-In2-xO3-y/Au Heterostructure Nanocolumnar Array Based Schottky Detector for Broad Band Recognition. AB - Glancing angle deposition (GLAD) was employed to fabricate the SiOx-In2-xO3-y axial heterostructure nanocolumn. The fabricated heterostructure nanocolumn was annealed at 550 degrees C for 1 hour at open air condition. The XRD analysis revealed the polycrystalline nature of the annealed SiOx-In2-xO3-y nanocolumn. The emission at 378 nm (~3.3 eV, FWHM 39.101 nm) from Photoluminescence (PL), corresponds to main band gap of In2O3. The In2-xO3-y-SiOx nanocolumn based Schottky detector processed maximum photoresponsivity of 199 A/W at 375 nm, as well as UV-Vis broad band detection. The high internal gain of ~659 at UV region (375 nm) was calculated for the device. The detector exhibited increase in photoresponsivity with decrease in room temperature upto 160 K, which further reduced at low temperature. A very sharp rise time (~1.82 s) and decay time (~1.78 s) was recorded at the applied potential of -2 V and -3 V. PMID- 26369206 TI - Reduction of Cr(VI) by Urea-Dispersed Nanoscale Zero-Valent Iron. AB - Urea was used to disperse nanoscale zero-valent iron (NZVI) for reduction of Cr(VI) to Cr(III) in aqueous solution. Scanning electron microscope and fourier transform-infrared spectra investigations demonstrated that urea could effectively increase the dispersion of NZVI resulting in more effective reduction sites (ERS) for Cr(VI) ions. Batch reduction experiments indicated that the reductive capacity of urea dispersed NZVI (UNZVI) was significantly improved, as the reductive efficiency reached 96.8% under optimal condition compared with the raw NZVI (72.14%). Additionally, the NZVI was stable for at least 28 days after urea treatment. The dispersion mechanism was proposed that the steric hindrance effect of the urea coating on the surface might play a key role in dispersing the NZVI particles. PMID- 26369207 TI - Bimetallic Pt-Au Nanocatalysts on ZnO/Al2O3/Monolith for Air Pollution Control. AB - The catalytic activity of a monolithic catalyst with nanosized Pt and Au particles on ZnO/Al2O3 (Pt-Au/ZnO/Al2O3/M) prepared by a wash-coat method was examined, specifically for toluene oxidation. Scanning electron microscopy image showed clearly the formation of a ZnO/Al2O3 layer on the monolith. Nanosized Pt Au particles on ZnO/Al2O3/M with different sizes could be found in the Pt Au/ZnO/Al2O3/M catalyst. The conversion of toluene decreased with increasing toluene concentration and was also largely affected by the feed flow rate. The Pt Au/ZnO/Al2O3/M catalysts prepared in this work have almost the same activity (molecules of toluene per second) compared with a powder Pt-Au/ZnO/Al2O3 catalyst with the same loadings of Pt and Au components; thus this catalyst could be used in controlling air pollution with very low concentrations and high flow rate. PMID- 26369208 TI - Electrical Property Variations in Organic Bistable Devices Utilizing CdSe/CdS/ZnS Core-Shell-Shell Nanoparticle Layer Embedded in a Polystyrene Layer Due to an Inserted WO3 Layer. AB - Organic bistable devices (OBDs) based on CdSe/CdS/ZnS core-shell-shell nanoparticles embedded in a polystyrene (PS) layer with an inserted WO3 layer were fabricated by using the spin coating method and the thermal evaporation. The current density-voltage (J-V) curves for the Al/CdSe/CdS/ZnS core-shell-shell nanoparticles embedded in PS layer/WO3/ITO devices with different thicknesses of WO3 layers exhibited electrical bistabilities. Simulated J-V curves for the OBDs containing CdSe/CdS/ZnS core-shell-shell nanoparticles were in reasonable agreement with the experimental results. The simulated J-V characteristics for the OBDs at various trap densities utilizing the double Gaussian distribution showed that the current level decreased with increasing shallow trap density and that the transition voltage increased with increasing deep trap density. PMID- 26369209 TI - Microstructure and Mechanical Properties of Ultra-Fine Grain Al-Zr Alloy Fabricated by Mechanical Alloying Process. AB - The ultra-fine grain Al-4Zr alloy has been successfully fabricated by a mechanical alloying process. The intermetallic Al3Zr phases strongly enhance the mechanical properties of Al-based alloy and prevent grain growth of alloy. The phase stability and transformation during mechanical alloying process have been investigated. The ultra-fine grain alloy has been successfully obtained. The thin film of Al-4Zr alloy has been observed by a transmission electron microscope. The equivalent grain size of as-milling specimen is 55 nm. After milling process, the specimens were heat treated at 350 degrees C to 650 degrees C. The equivalent grain size of heat treated specimens were 80 nm at 350 degrees C and 130 nm at 650 degrees C. Some of Zr atoms were dissolved into the Al matrix and most of them reacted with hydrogen produced by decomposition of PCA to form ZrH2 during mechanical alloying process. These ZrH2 hydrides decomposed gradually after the heat treatment. Stable A13Zr with a D023 structure was formed by heat treatment at temperature of 550 degrees C. PMID- 26369210 TI - Nano-Particle Formation of Mn/HA on the Ti-35Ta-xNb Alloy by Electrochemical Methods. AB - In this study, nano-particle formation of Mn/HA on the Ti-35Ta-xNb alloy by electrochemical methods has researched using various experiments. These alloys were performed by arc-melting furnace and then heat treated for 1000 degrees C at 12 h in Ar gas atmosphere and quenched at 0 degrees C water. Hydroxyapatite precipitation has been synthesized from 5 mM Ca(NO3)2 . 4 H2O+3 mM NH4H2PO4 at 80+/-1 degrees C. Manganese doped Hydroxyapatite precipitation has been synthesized from 4.95 mM Ca(NO3)2 . 4 H2O+3 mM NH4H2PO4+0.05 mM MnCl2 . 4 H2O at 80+/-1 degrees C. Morphology and structure were examined by FE-SEM, EDS and XRD. The microstructure of Ti-35Ta-xNb alloys was transformed from a phase to alpha phase as Nb content increased. The nano-scale HA shapes were plate-like precipitates and Mn doped HA shapes were net-like precipitates on Ti-35Ta-xNb alloys, and Ca, P and Mn peaks were detected on the Mn/HA deposited surface. PMID- 26369211 TI - Electrochemical Deposition of Si-Ca/P on Nanotube Formed Beta Ti Alloy by Cyclic Voltammetry Method. AB - The purpose of this study was to investigate electrochemical deposition of Si Ca/P on nanotube formed Ti-35Nb-10Zr alloy by cyclic voltammetry method. Electrochemical deposition of Si substituted Ca/P was performed by pulsing the applied potential on nanotube formed surface. The surface characteristics were observed by field-emission scanning electron microscopy, X-ray diffractometer, and potentiodynamic polarization test. The phase structure and surface morphologies of Si-Ca/P deposition were affected by deposition cycles. From the anodic polarization test, nanotube formed surface at 20 V showed the high corrosion resistance with lower value of Icorr, I300, and Ipass. PMID- 26369212 TI - Microbial Synthesis and Characterization of Superparamagnetic Zn-Substituted Magnetite Nanoparticles. AB - The objective of this study is to examine microbial synthesis of magnetite and Zn substituted magnetite nanoparticles by iron-reducing bacteria (Clostridium sp.) enriched from intertidal flat sediments. The magnetite nanoparticles were synthesized by the bacteria under anaerobic conditions at room temperature using akaganeite (beta-FeOOH) or Zn-substituted akaganeite (beta-ZnxFe1-xOOH) as a magnetite precursor during glucose fermentation. This research indicates that fermentation processes can establish the microbial synthesis of magnetite and Zn substituted magnetite when conditions are at room temperature, ambient pressure, and pH values near neutral to slightly basic (pH < 8). PMID- 26369213 TI - Surface Characterization and Osteoconductivity Evaluation of Micro/Nano Surface Formed on Titanium Using Anodic Oxidation Combined with H2O2 Etching and Hydrothermal Treatment. AB - In this study, surface characteristics and osteoconductivity were investigated for the micro/nanostructured oxide layers fabricated on titanium using anodic oxidation (ANO), chemical etching (Et), and hydrothermal treatment (HT). Commercially pure titanium (CP-Ti) disks were anodic-oxidized using DC-type power supply in 1 M phosphoric acid electrolyte (P-ANO group). These specimens were further chemically etched using 30% H2O2 solution at 60 degrees C for 10 min (P ANO-Et group). The P-ANO-Et-HT group was fabricated by hydrothermally treating the P-ANO-Et specimens in phosphorus-containing alkaline solution at 190 degrees C for 8 hrs. The P-ANO group showed a porous surface that was evenly covered with micro- and sub-micro pores. The size of these pores was decreased in the P-ANO-Et group. The P-ANO-Et-HT group showed a porous surface that was covered with nano sized crystallites. Anatase TiO2 structure was observed in P-ANO-Et-HT group. The results of XPS demonstrated that the P-ANO-Et-HT group had a well-crystallized TiC2 structure, while the P-ANO and P-ANO-Et groups had an amorphous and phosphate-containing structure. Hydrophilicity of the P-ANO-Et-HT group was the highest. After MG63 osteoblast-like cells were cultured on the specimens for 3 hrs, SEM images of the cells cultured on P-ANO-Et-HT group specimens showed low initial adhesion. However, the osteoconductivity of these specimens increased more rapidly compared to that of the micro-structured surfaces. These results could be applied to fabricate titanium implants with an optimum micro/nano surface for enhancing their osteoconductivity. PMID- 26369214 TI - Effect of Ionic Liquids on Synthesis of Ag/TiO2 Catalyst in Water Electrolysis. AB - Effective Ag/TiO2 catalyst was synthesized using ionic liquids in water electrolysis. Silver was impregnated on TiO2 particles with various ionic liquids to examine the electrocatalytic activity in acid solution. Among the ionic liquids, [Bmim][CF3SO3] was most effective to prepare Ag/TiO2 particle in cyclic voltammograms. The current density over the sample was higher than 0.02 A/cm2. Furthermore, the catalyst synthesized using TiO2 particle prepared using binary ionic liquid (Ag/TiO2-IL) showed better electocatalytic activity, 0.023 A/cm2, under identical conditions. PMID- 26369215 TI - Preparation of 13X from Waste Quartz and Photocatalytic Reaction of Methyl Orange on TiO2/ZSM-5, 13X and Y-Zeolite. AB - TiO2 photocatalytic reactions not only remove a variety of organic pollutants via complete mineralization, but also destroy the bacterial cell wall and cell membrane, thus playing an important bactericidal role. However, the post filtration procedures to separate nanometer-levels of TiO2 and the gradual inactivity of photocatalyst during continuous use are defects that limit its application. In this case, we propose loading TiO2 on zeolite for easy separation and 13X is considered as a promising one. In our study, 13X-zeolite was prepared by a hydrothermal method and the source of Si was extracted from waste quartz sand. For comparison, commercial zeolite with different microporous and mesoporous diameters (ZSM-5 and Y-zeolites) were also used as TiO2 supports. The pore size of the three kinds of zeolites are as follows: Y-zeolite > 13X > ZSM-5. Different TiO2 loading content over ZSM-5, 13X and Y-zeolite were prepared by the sol-gel method. XRD, FTIR, BET, UV-vis, TGA and SEM were used for investigation of material characteristics. In addition, the efficiencies of mineralization and photodegradation were studied in this paper. The effects of the loading ratio of TiO2 over zeolites, initial pH, and concentration on photocatalytic performance are investigated. The relationship between best loading content of TiO2 and pore size of the zeolite was studied. The possible roles of the ZSM-5, 13X-zeolites and Y-zeolites support on the reactions and the possible mechanisms of effects were also explored. The best loading content of TiO2 over ZSM-5, 13X and Y zeolite was found to be 50 wt%, 12.5 wt% and 7 wt%, respectively. The optimum pH condition is 3 with TiO2 over ZSM-5, 13X-zeolites and Y-zeolites. The results showed that the degradation and mineralization efficiency of 12.5 wt%GT13X (TiO2 over 13X) after 90 min irradiation reached 57.9% and 22.0%, which was better than that of 7 wt%GTYZ (TiO2 over Y-zeolites) while much lower than that of 50 wt%GTZ (TiO2 over ZSM-5). The materials were recycled four times while the degradation was remained at a higher level. PMID- 26369216 TI - Selective Chlorination of Toluene to p-Chlorotoluene Catalyzed by Nanosized Zeolite K-L Catalysts. AB - Nanosized zeolite K-L catalysts were synthesized by the hydrothermal method starting from silica sol and potassium aluminate. The crystallinities of the zeolite K-L catalysts increased with increasing the SiO2/Al2O3 mole ratio of reaction solution and prolonging the autoclaving time. Nanosized and well dispersed zeolite K-L catalysts were synthesized when the SiO2/Al2O3 mole ratio was more than 26:1. Well-crystallized and nanosized zeolite K-L catalysts showed high catalytic activity for the chlorination of toluene to p-chlorotoluene. When the nanosized zeolite K-L catalyst was synthesized with the SiO2/Al2O3 mole ratio of 31:1 at the autoclaving temperature of 150 degrees C for 96 h, the selectivities of p-chlorotoluene and o-chlorotoluene were 76.2% and 20.0%, respectively, at the complete conversion of toluene. PMID- 26369217 TI - Effect of Al and Y2O3 on Mechanical Properties in Mechanically Alloyed Nanograin Ni-Based Alloys. AB - The effects of aluminum and Y2O3 on the mechanical properties in nano grain Ni based alloys have been investigated. The test specimens are prepared by mechanical alloying at an Ar atmosphere. The addition of Y2O3 and Al may cause an increase in the tensile strength at room temperature, 400 degrees C and 600 degrees C. However, it was confirmed that the increase of tensile strength at room temperature and 400 degrees C was predominantly caused by addition of Y2O3, while that at 600 degrees C was mainly due to addition of Al. These results can be attributed to the dispersion strengthening of Y2O3, preventing the formation of Cr2O3 and the change of fracture mode at 600 degrees C by the addition of Al. PMID- 26369218 TI - Preparation and Characterisation of Hydroxyapatite Coatings on Nanotubular TiO2 Surface Obtained by Sol-Gel Process. AB - Hydroxyapatite (HA) coating on titanium dioxide (TiO2) nanotubular surface has been developed to complement the defects of both TiO2 and HA. A sol-gel processing technique was used to coat HA on TiO2 nanotubular surface. All the titanium discs were blasted with resorbable blast media (RBM). RBM-blasted Ti surface, anodized Ti surface, and sol-gel HA coating on the anodized Ti surface were prepared. The characteristics of samples were observed using scanning electron microscopy and X-ray photoemission spectroscopy. Biologic responses were evaluated with human osteosarcoma MG63 cells in vitro. The top of the TiO2 nanotubes was not completely covered by HA particles when the coating time was less than 60 sec. It was demonstrated the sol-gel derived HA film was well crystallized and this enhanced biologic responses in early stage cell response. PMID- 26369219 TI - Rapid Polyol-Assisted Microwave Synthesis of Nanocrystalline LiFePO4/C Cathode for Lithium-Ion Batteries. AB - Nanocrystalline LiFePO4/C has been synthesized under a very short period of time (90 sec) using a polyol-assisted microwave heating synthesis technique. The X-ray diffraction (XRD) data indicates that the rapidly synthesized materials correspond to phase pure olivine. Post-annealing of the as-prepared sample at 600 degrees C in argon atmosphere yields highly crystalline LiFePO4/C. The morphology of the samples studied using scanning electron microscopy (SEM) reveals the presence of secondary particles formed from aggregation of primary particles in the range of 30-50 nm. Transmission electron microscopy (TEM) images reveal a thin carbon layer coating on the surface of the primary particle. The charge/discharge studies indicate that the as-prepared and annealed LiFePO4/C samples delivered initial discharge capacities of 126 and 160 mA h g-1, respectively, with good capacity retentions at 0.05 mA cm-2 current densities. The post-annealing process indeed improves the crystallinity of the LiFePO4 nanocrystals, which enhances the electrode performance of LiFePO4/C. PMID- 26369220 TI - The Fabrication of Flow Field Plates for Direct Methanol Fuel Cell Using Lithography and Radio Frequency Sputtering. AB - This study uses lithography to etch flow fields on a single side of a printed circuit board (PCB) and combines a flow field plate with a collector plate to make innovative anode flow field plates and cathode flow field plates for a direct methanol fuel cell (DMFC). TiO2 thin film is also sputtered on the anode flow field plate using radio frequency (RF) sputtering. The experimental results show that the prepared DMFC has a better maximum power density of 11.928 mW/cm2. Furthermore, when a TiO2 thin film is sputtered on the flow field plate of the assembled DMFC, the maximum power density is 14.426 mW/cm2, which is actually 21% more than that for a DMFC with no TiO2 thin film coated on the flow field plate. PMID- 26369221 TI - Functionalization of Natural Graphite for Use as Reinforcement in Polymer Nanocomposites. AB - Graphite is a naturally abundant material that has been used as reinforcing filler to produce polymeric nanocomposites for various applications including automotive, aerospace and electric-electronic. The objective of this study was to develop methodologies of graphite nanosheets preparation and for incorporation into polymer matrices. By means of different chemical and physical treatments, natural graphite was modified and subsequently characterized by X-ray diffraction (XRD), infrared spectroscopy (FTIR), scanning electron microscopy (SEM), thermogravimetry (TGA) and the particle size determination. The results obtained clearly show that after the treatments employed, polar chemical groups were inserted on the natural graphite surface. Nanosized graphite particles of high aspect ratio were obtained. PMID- 26369222 TI - Effect of Annealing Temperature on the Performance of SnO2 Thin Film Transistors Prepared by Spray Pyrolysis. AB - We fabricated SnO2 thin film transistors on thermally oxidized p-type silicon substrates by low-cost spray pyrolysis. The effect of annealing temperatures on electrical characteristics of SnO2 thin film transistors were investigated. Thermal annealing at higher temperatures induced a negative shift of the threshold voltage (VT) and an increase in the saturation mobility. It was found that the device annealed at 450 degrees C exhibited a good electrical performance with the field-effect mobility of 0.19 cm2/Vs, the threshold voltage of 2.5 V, and the on/off current ratio of 10(3). PMID- 26369223 TI - Development of Antigen-Immobilized Metallothionein Sensor that Exploits Gold Nanoparticle-Based Enhancement of Signal. AB - An antigen-immobilized indirect-competitive immunosensor that detects metallothionein (MT), a potent biomarker of contamination with heavy metals, was developed exploiting enhancement of signal based on an additional binding of gold nanoparticles to an anti-MT antibody through the biotin-avidin interaction. The sensor was constructed by the immobilization of MT at 1 mg/mL on a 9-MHz quartz crystal microbalance and the concentration of the antibody for competitive reaction was optimized as 10 ug/mL based on the degree of sensor response. At this moment, the control response of the sensor obtained with enhancement of signal was 343.8 Hz and was larger than that without enhancement of signal 2.47 fold. The sensor responses decreased gradually with increasing analyte concentrations, and a linear relationship between analyte concentration and sensor response was acquired in the range of 0.005-1 ng/mL MT in double logarithmic scales with a correlation coefficient (r) of 0.9858. The limit of detection of the present sensor was presumed to be present below 5 pg/mL MT. PMID- 26369224 TI - Glycothermal Synthesis and Photocatalytic Properties of Highly Crystallized Anatase TiO2 Nanoparticles. AB - Highly crystallized anatase TiO2 nanoparticles were synthesized at a temperature as low as 120 degrees C through a glycothermal reaction using amorphous titanium hydrous gel as precursor and 1,4-butanediol and water as solvent. X-ray diffraction (XRD) and transmission electron microscopy (TEM) data support that the glycothermal processing method provides a simple low-temperature route for producing highly crystallized anatase TiO2 nanoparticles without pH adjustment. It is demonstrated that the shape and dispersability of TiO2 nanoparticles can be controlled by the reaction conditions, such as the reaction temperature and variation of the volume ratio of 1,4- butanediol/water (B/W). It was observed that TiO2 samples glycothermally prepared at 220 degrees C and the B/W ratio of 8/0 showed excellent photocatalytic behavior. The high activity is attributed to the high crystallinity and bipyramidal shape of the particles, which have fewer defects and more active {101} surfaces. PMID- 26369225 TI - The Performance of Geopolymers Activated by Sodium Hydroxide. AB - Geopolymers, a group of promising environmentally friendly materials that can work as cement substitutes, should be fabricated from SiO2-Al2O3-CaO mixtures containing large amounts of amorphous phases to ensure optimal chemical and physical properties. In this study, it was shown that geopolymers with enhanced mechanical strengths, as high as 115 MPa, could be obtained from perfectly amorphous slag from spent catalyst (SSC) discharged during automobile catalyst recycling. Geopolymer processing involved alkali-activation using a 16 M NaOH solution of pH13. The varying SSC grain size was the main experimental factor of interest, in combination with curing temperature and aging time. Variations in the mechanical strengths of the resulting geopolymers are explained by the occurrence of 10-50 nm-sized crystals and the presence of voids and pores dozens to hundreds of micrometers in size. PMID- 26369226 TI - Bioavailability of the Nano-Unit 14C-Agrochemicals Under Various Water Potential. AB - The study was conducted to investigate the effects of water potential on bioavailability of the nano-unit 14C-cafenstrole, 14C-pretilachlor, 14C benfuresate, 14C-simetryn and 14C-oxyfluorfen applied with or without dimepiperate or daimuron under various water potential conditions. The highest bioavailable concentration in soil solution (BCSS) was found at 60% soil moisture, while the lowest occurred at 50% soil moisture for soil-applied alone or in combination. All water potential conditions differed significantly from each other with variations in total bioavailable amount in soil solution (TBSS) when either dimepiperate or daimuron were added to the soil, and changes were directly proportional to variations in water potential. Across all treatments, TBSS at 80% soil moisture was three to four times greater than that at 50% soil moisture when applied alone or in combination with dimepiperate or daimuron. Cafenstrole and simetryn had distribution coefficient (Kd) values <64 ml g-1 and a TBSS ranging from 10 to 44 ng g-1 soil, regardless of water potential conditions applied alone or in combination. Pretilachlor and benfuresate had Kd values <15 ml g-1 and a TBSS range of 38 to 255 ng g-1 soil when applied with or without dimepiperate or daimuron. PMID- 26369228 TI - Structural Effect of Palladium on Carbon Catalyst for Hexafluoropropylene Hydrogenation. AB - Palladium was impregnated on carbon particles with various structures using 1 hexyl-3-methylimidazolium hexafluorophosphate ([Hmim][PF6]) to synthesize a catalyst for hexafluoropropylene hydrogenation. Under the identical reaction conditions (1 bar and 120 degrees C), the catalyst with mesoporosity (pore size > 500 nm) showed higher than 80% reactant conversion. However, the conversion over the catalyst possessed small pore size was very low. Moreover, the catalyst prepared with ionic liquids was more stable than without ionic liquids. PMID- 26369227 TI - Preparation and Characterization of Low Molecular Weight Heparin by Liquid Phase Plasma Method. AB - An liquid phase plasma process system was applied to the production of low molecular weight heparin. The molecular weight of produed heparin decreased with increasing liquid phase plasma treatment time. The abscission of the chemical bonds between the constituents of heparin by liquid phase plasma reaction did not alter the characteristics of heparin. Formation of any by-products due to side reaction was not observed. It is suggested that heparin was depolymerized by active oxygen radicals produced during the liquid phase plasma reaction. PMID- 26369229 TI - The Influence of Surface-Active Agent on the Micro-Morphology and Crystallinity of Spherical Hexagonal Boron Nitride. AB - This search used the low-cost boric acid and borax as a source of boron, urea as a nitrogen source, surface-active agent Dodecyl benzenesulfonic acid (SDBS) as a dispersant, and thus prepared different micro-morphology and crystallinity hexagonal boron nitride powders under a flowing ammonia atmosphere at a nitriding temperature of 900 degrees C. The effect of the surface-active agent (SDBS) content on the crystallinity and micro-morphology of hexagonal boron nitride powders was studied, and the corresponding relationship between micro-morphology and crystallinity was explored. The results showed that under a certain synthetic process (900 degrees C for 3 h), the surfactant content had affected the crystallinity and micro-morphology of h-BN powders. Without the added surfactant, the graphitization index (GI) was 3.61, and micro-morphology of h-BN powders. was spherical, the distribution of ball diameters was uneven, and there was also significant particle agglomeration, with some particles even exhibiting adhesion, sintering necks, and high sphericity and diameter. When the added SDBS percentages were 2%, 4% and 6%, the graphitization index (GI) decreased to 2.98, 2.58 and 2.41 respectively: the corresponding crystallinity improved significantly. When the surfactant SDBS content was higher (10%), the diameter distribution of the h-BN powders was even, but there was evidence of agglomeration of particles and particle adhesion. The crystallinity decreased when the GI value was increased to 4. When the surfactant SDBS content was 6%, the dispersion of h-BN powders was at its optimum, and the particle size distribution was at its most uniform. Meanwhile the GI value was at its lowest, and the crystallinity at its highest. PMID- 26369230 TI - Synthesis and Electrochemical Analysis of Algae Cellulose-Polypyrrole-Graphene Nanocomposite for Supercapacitor Electrode. AB - A novel nanocomposite has been developed using extracted cellulose from marine algae coated with conductive polypyrrole and graphene nanoplateletes. The nanocomposite fabricated via in situ polymerization was used as an electrode for a supercapacitor device. The nanocomposite material has been electrochemically characterized using cyclic voltammetry to test its potential to super-capacitive behavior. The specific capacitance of polypyrrole-graphene-cellulose nanocomposite as calculated from cyclic voltammetry curve is 91.5 Fg-1 at the scan rate 50 mV s-1. Transmission electron microscope images show the polymerized polypyrrole -graphene coated cellulosic nanofibers. Scanning electron microscope images reveal an interesting "necklace" like beaded morphology on the cellulose fibers. It is observed that the necklace like structure start to disintegrate with the increase in graphene concentration. The open circuit voltage of the device with polypyrrole-graphene-cellulose electrode was found to be around 225 mV and that of the polypyrrole-cellulose device is only 53 mV without graphene. The results suggest marked improvement in the performance of the nanocomposite supercapacitor device upon graphene inclusion. PMID- 26369231 TI - Preparation of Gold Nanorods Using 1,2,4-Trihydroxybenzene as a Reducing Agent. AB - We report an improved method for synthesizing gold nanorods (GNRs) by using 1,2,4 trihydroxybenzene as a reducing agent. The method allows a rich array of monodispersed GNRs with longitudinal surface plasmon resonance (LSPR) tunable from 698 to 913 nm to be generated. A large range of diameter distribution of GNRs from 9.3 to 32.2 nm with exceptional monodispersity can be well prepared by this method. These findings indicate that this method has greater performance in controlling the morphology of GNRs than that of traditional approaches with ascorbic acid as a reductant. PMID- 26369232 TI - HEALTH INSURANCE INFORMATION-SEEKING BEHAVIORS AMONG INTERNET USERS: AN EXPLORATORY ANALYSIS TO INFORM POLICIES. AB - The purpose of this study was to explore characteristics of Internet users who seek health insurance information online, as well as factors affecting their behaviors in seeking health insurance information. Secondary data analysis was conducted using data from the 2012 Pew Internet Health Tracking Survey. Of 2,305 Internet user adults, only 29% were seeking health insurance information online. Bivariate analyses were conducted to test differences in characteristics of those who seek health insurance information online and those who do not. A logistic regression model was used to determine significant predictors of health insurance information-seeking behavior online. Findings suggested that factors such as being a single parent, having a high school education or less, and being uninsured were significant and those individuals were less likely to seek health insurance information online. Being a family caregiver of an adult and those who bought private health insurance or were entitled to Medicare were more likely to seek health insurance information online than non-caregivers and the uninsured. The findings suggested the need to provide quality health insurance information online is critical for both the insured and uninsured population. PMID- 26369233 TI - PROSTATE CANCER SCREENING: PSA TEST AWARENESS AMONG ADULT MALES. AB - The overall purpose of this study was to determine whether visits to the doctor in the last 12 months, education level, and annual household income for adult males increased the awareness of prostate-specific antigen (PSA) tests. The effect of these factors for the knowledge of PSA exams was performed using statistical analysis. A retrospective secondary database was utilized for this study using the questionnaire in the California Health Interview Survey from 2009. Based on this survey, annual visits to the doctor, higher educational levels attained, and greater take-home pay were statistically significant and the results of the study were equivalent to those hypothesized. This also reflects the consideration of marketing PSA blood test screenings to those adult males who are poor, uneducated, and do not see the doctor on a consistent basis. PMID- 26369234 TI - PAYER SOURCE FOR SINGLE, ELDERLY WOMEN IN NURSING HOMES. AB - This study seeks to determine the payer source for single, elderly women in nursing homes by using secondary data from the 2004 National Nursing Home Survey was extracted and analyzed for the aforementioned hypotheses. By determining the payer source for single, elderly women, the next generation of women can prepare for high nursing home costs by saving earlier or investing in long-term care insurance. The analyses indicated self-pay and Medicaid was the primary sources for elderly women in nursing homes. Marital status did not have an impact on the payer source for elderly women. Single women did not have different payer sources than married elderly women. However, the study did not focus on payer sources for single, elderly women in nursing homes, but the demographic population as a whole. PMID- 26369235 TI - AFFORDABLE HOUSING, HOMELESSNESS, AND MENTAL HEALTH: WHAT HEATH CARE POLICY NEEDS TO ADDRESS. PMID- 26369236 TI - MEDICAL BRIGADES, GLOBAL HEALTH AND THE UNITED NATIONS: MILLENNIUM DEVELOPMENT GOALS AND DEVELOPING NATIONS. AB - Recently, recommendations have been made that global health initiatives change their focus from disease specific intervention to bolstering health systems and general health care. The aim of this is to ultimately increase access to primary care, clean water, education, hygiene, and prevent malnutrition, among other goals. While many major global health initiatives have followed this trend, so have many smaller scale programs including short-term medical brigades. Despite a trending increase in the number of privately run short-term medical brigades, until recently, little research has been done on the potential positive and negative effects that can arise from such programs. Now, guidelines have been initiated to create well-structured programs. When followed, these smaller scale initiatives can be successful in helping increase access to healthcare, sustainably strengthening communities in terms of general health. While recent legislation in the United States has addressed domestic policy in the Patient Protection Affordable Care Act of 2010 (ACA), the ACA should also consider some of the basic "sustainable" policies being implemented by international health care providers. PMID- 26369237 TI - CALIFORNIA STATE UNIVERSITY CATASTROPHIC (CAT) LEAVE DONATION PROGRAM: DEMOGRAPHICS, ECONOMIC SECURITY, AND SOCIAL EQUITY. AB - The California State University (CSU) Chancellor's Office reached an agreement with all CSU collective bargaining units and Employee Relations on a uniform Catastrophic (CAT) Leave Donation Program in 1992. The CAT Leave Donation Program allows employees to donate sick and/or vacation leave credits to employees who are incapacitated due to a catastrophic illness or injury and have exhausted all of their own leave credits. This also extends to employees with whom family illnesses are deemed catastrophic, thus requiring the employee to care for an immediate family member. Stakeholders include union represented employees who accrue leave credits as well as any employee who receives or donates hours of leave credits in the program. Other stakeholders include the family members and program administrators. PMID- 26369238 TI - [Novosibirsk Research Hygiene Institute - 85 years serving sanitary epidemiologic well-being of Siberia population]. AB - The authors present review ot themes covered by Novosibirsk Research Hygiene Institute and the study results obtained over recent years. Evidences are that industrial Siberian centers demonstrate general positive changes in environmental pollution decrease and better health state of children and adolescents, but the situation remains warning about medical and sanitary care for workers engaged into hazardous work conditions, about lower diagnostic coverage of occupational diseases in periodic medical examinations. Facts are that qualified early diagnosis of primary signs of workers' disablement and opportune rehabilitation and preventive treatment enable to stop occupational diseases formation. PMID- 26369239 TI - [Features of vegetative regulation in occupational dorsopathies]. AB - Based on spectral analysis of heart rhythm variability, studies covered changes in vegetative regulation in patients with occupational dorsopathies of cervical and lumbar regions. Findings are that 75% of patients with occupational dorsopathies have marked vegetative disorders - insufficient activity of sympathetic nervous system and drastic dominance of parasympathetic regulatory mechanisms due to pathologic vertebrogenous influences on peripheral vegetative structures. The most informative stress testing to reveal vegetative dysfunction in patients with occupational dorsopathies is flexion test. Individuals with occupational dorsopathies and dominant parasympathetic regulatory mechanisms have more severe prognosis due to more frequent severe degenerative and dystrophic spinal changes. PMID- 26369240 TI - [Occupational neurosensory deafness in civil aircraft crew members]. AB - The article covers data on prevalence of neurosensory deafness among civil aircraft crew members. The study revealed high level of neurosensory deafness in civil aircraft crew members, averaging to 50.8% in neurosensory deafness structure among noise-related occupations. Arterial hypertension appeared to be the most prevalent concurrent disease in civil aircraft crew members with neurosensory deafness, found in 47.5% of the patients examined - that considers arterial hypertension as a factor of neurosensory deafness progression. PMID- 26369241 TI - [Clinical and hygienic aspects of occupational neurosensory deafness in civil aviation flight personnel]. AB - The article covers implementation of regulatory and legal concepts in prevention of risk caused by hazardous effects of noise in civil aviation flight personnel. The authors analyzed case histories of civil aviation flight personnel patients examined in occupational diseases clinic, with first diagnosed occupational neurosensory deafness. PMID- 26369242 TI - [Forecasting formation and course of vibration disease on basis of genetic metabolic markers study]. AB - Analyzing distribution of genotype polymorphism occurrence of Pro l98Leu gene of GPX1 (glutathion peroxidase) and Ala 16 Val gene of MnSOD (superoxide dismutase), the authors presented major mechanisms and leading pathogenetic factors of vibration disease formation and course in post-contact period. The article covers also results of metabolic processes evaluation in patients with varying resistence to occupational vibration, for forecasting its course after discontinued contact with the factor. PMID- 26369243 TI - [Health state in Tyva guttural singers]. AB - The article deals with results of cardiorespiratory status study in professional guttural singers. Findings are that long length of service in "hoomey" style professional guttural singers results in lower external respiration parameters and RBC saturation values. Ultrasound investigation demonstrates reliably more frequent left ventricle hypertrophy. The results obtained necessitate specification of programs for complex evaluation of occupational risks and for prevention of occupational and occupationally mediated diseases in guttural singers. PMID- 26369244 TI - [Spirometry and veloergometry in evaluating physical performance of individuals exposed to organic solvents]. AB - Increased length of service in house-painters causes longer half-periods of adaptation and recovery, larger their total, lower coefficient of recovery and lower coefficient of myocardial resources expenditure. That indicates lower efficiency of heart action under exertion, poor adaptive reactions to physical exertion and latent heart failure formation. PMID- 26369245 TI - [Experience of local treatment in occupational therapy]. AB - The article covers topics of possible local methods to treat pain in occupational diseases. Local pain treatment was implemented in patients of occupational diseases clinic, having locomotory and peripheral nervous system diseases. PMID- 26369246 TI - [cardiovascular system and cognitive disorders in male drivers]. AB - The authors found statistically significant differences in cognitive tests results between group of drivers and reference group (p = 0,021). Correlation analysis proves statistically reliable relationship between cognitive functions and hemodynamic as well as morphologic parameters of cardiovascular system. PMID- 26369248 TI - [Albert Sarkisovitch Kazarian (to the 70th birithday)]. PMID- 26369247 TI - [Health state in women engaged in professional military service in European North]. AB - The authors analysed health state and morbidity of women engaged into professional navy service in North Fleet, age features of health state in these servicewomen, and results of medical stationary examination and checkup results, regular medical examination results and the servicewomen morbidity over 12 years (about 15.5 thousand cases), and 697 reports on the servicewomen diseases according to military medical (navy) commission. The article covers causes of changes in navy fitness category for the servicewomen, analysis of comorbidity, suggestions of new approaches to comorbidity analysis. PMID- 26369249 TI - [Artamonova Volya Georgievna]. PMID- 26369250 TI - [Piktushanskaya Irina Nikolaevna]. PMID- 26369251 TI - Transcutaneous Electrical Stimulation Increased Nitric Oxide-Cyclic GMP Release Biocaptured Over Skin Surface of Pericardium Meridian and Acupuncture Points in Humans. AB - OBJECTIVES: The purpose of this study was to consecutively capture and quantify nitric oxide (NO) and cGMP, the second messenger of NO, over the skin surface of acupuncture points (acupoints), meridian line without acupoint, and non-meridian control regions of the Pericardium meridian (PC) in humans, and investigate their response to transcutaneous electrical nerve stimulation (TENS) . DESIGN, SETTING, AND MAIN OUTCOME MEASURES: Adhesive biocapture tubes were attached to the skin surface along PC regions and injected with 2-Phenyl-4,4,5,5 tetramethylimidazoline-3-oxide-1-oxyl solution, an NO-scavenging compound, contacting the skin surface for 20 minutes each during 4 consecutive biocapture intervals. TENS (1.0 mA, 6 Hz, 1.0 msec duration) was applied over acupoints PC 8 and PC 3 during the 2nd biocapture for 20 min. Total nitrite and nitrate (NO(x) ), the stable metabolic products of NO, and cGMP in biocaptured samples were quantified using chemiluminescence and ELISA. RESULTS: NO(x)- levels in the 1st biocapture over PC regions are almost two fold higher compared to subsequent biocaptures and are higher over PC acupoints versus non-meridian control region. Following TENS, NO(x)- concentrations over PC regions were significantly increased, and cGMP is predominantly released from the skin surface of PC acupoints. CONCLUSIONS: TENS induces elevations of NO-cGMP concentrations over local skin region with a high level at acupoints. The enhanced signal molecules improve local circulation, which contributes to beneficial effects of the therapy. PMID- 26369252 TI - Beneficial and Adverse Effects of Electro-acupuncture Assessed in the Canine Chronic Atrio-ventricular Block Model Having Severe Hypertension and Chronic Heart Failure. AB - Regarding the effects of electro-acupuncture for severe hypertension, we assessed its acute cardiovascular consequences with 4 subjects of the chronic atrioventricular block dogs having severe hypertension and chronic heart failure. The electro-acupuncture consisting of 2 mA at 2 Hz frequency was carried out for 30 min at Renying (ST-9) and Taichong (LR-3) every other day. Seven sessions were performed within 2 weeks. In the 1st and 7th sessions, the animals were anesthetized with pentobarbital to analyze the effects of the electro-acupuncture on cardiovascular variables. No significant change was detected in any of the basal control values of the cardiohemodynamic or electrophysiological variables between the 1st and 7th sessions. During the 1st session, electo-acupuncture produced a peak increase in mean blood pressure by 8.7% at 35 min (p < 0.05), whereas during the 7th session the peak increase was 6.5% at 35 min (p = 0.06). There was no significant change in the cardiac output, total peripheral resistance, a product of the heart rate and systolic blood pressure (= double product) reflecting myocardial oxygen consumption, QRS width or QT interval during the electrical stimulation in the 1st or 7th session. The results suggest that electroacupuncture may not exert lethal adverse effect except the vasopressor response, but that it can decrease the treatment-induced sympathetic response including vasopressor reaction and tachycardia. Since electro acupuncture may have some potential to induce hypertensive crisis at the beginning, clinicians have to pay attention on its use for patients with hypertension. PMID- 26369253 TI - Simple New Method of Detecting Lies By Identifying Invisible Unique Physiological Reflex Response Appearing Often Less Than 10-15 Seconds on the Specific Parts of Face of Lying Person; Quick Screening of Potential Murderers & Problematic Persons. AB - Frequently, we cannot find any significant visible changes when somebody lies, but we found there are significant invisible changes appearing in specific areas of the face when somebody lies and their location often depends on whether the lie is serious with or without physical violence involvement. These abnormalities were detected non-invasively at areas: 1) lobules and c) a small round area of each upper lateral side of forehead; 2) the skin between the base of the 2 orifices of the nose and the upper end of upper lip and 3) Alae of both sides of nose. These invisible significant changes usually last less than 15 seconds after telling a lie. In these areas, Bi-Digital O-Ring Test (BDORT), which received a U.S. Patent in 1993, became significantly weak with an abnormal value of (-)7 and TXB2, measured non-invasively, was increased from 0.125-0.5ng to 12.5-15ng (within the first 5 seconds) and then went back down to less than 1ng (after 15 seconds). These unique changes can be documented semi-permanently by taking photographs of the face of people who tell a lie, within as short as 10 seconds after saying a lying statement. These abnormal responses appear in one or more of the above-mentioned 3 areas 1), 2) & 3). At least one abnormal pupil with BDORT of (-)8-(-)12 & marked reduction in Acetylcholine and abnormal increase in any of 3 Alzheimer's disease associated factors Apolipoprotein (Apo) E4, beta-Amyloid (1 42), Tau protein, viral and bacterial infections were detected in both pupils and forehead of murderers and people who often have problems with others. Analysis of well-known typical examples of recent mass murderers was presented as examples. Using these findings, potential murderers and people who are very likely to develop problems with others can be screened within 5-10 minutes by examining their facial photographs and signatures before school admission or employment. PMID- 26369254 TI - How Consumers and Physicians View New Medical Technology: Comparative Survey. AB - BACKGROUND: As a result of the digital revolution coming to medicine, a number of new tools are becoming available and are starting to be introduced in clinical practice. OBJECTIVE: We aim to assess health care professional and consumer attitudes toward new medical technology including smartphones, genetic testing, privacy, and patient-accessible electronic health records. METHODS: We performed a survey with 1406 health care providers and 1102 consumer responders. RESULTS: Consumers who completed the survey were more likely to prefer new technologies for a medical diagnosis (437/1102, 39.66%) compared with providers (194/1406, 13.80%; P<.001), with more providers (393/1406, 27.95%) than consumers (175/1102, 15.88%) reporting feeling uneasy about using technology for a diagnosis. Both providers and consumers supported genetic testing for various purposes, with providers (1234/1406, 87.77%) being significantly more likely than consumers (806/1102, 73.14%) to support genetic testing when planning to have a baby (P<.001). Similarly, 91.68% (1289/1406) of providers and 81.22% (895/1102) of consumers supported diagnosing problems in a fetus (P<.001). Among providers, 90.33% (1270/1406) were concerned that patients would experience anxiety after accessing health records, and 81.95% (1149/1406) felt it would lead to requests for unnecessary medical evaluations, but only 34.30% (378/1102; P<.001) and 24.59% (271/1102; P<.001) of consumers expressed the same concerns, respectively. Physicians (137/827, 16.6%) reported less concern about the use of technology for diagnosis compared to medical students (21/235, 8.9%; P=.03) and also more frequently felt that patients owned their medical record (323/827, 39.1%; and 30/235, 12.8%, respectively; P<.001). CONCLUSIONS: Consumers and health professionals differ significantly and broadly in their views of emerging medical technology, with more enthusiasm and support expressed by consumers. PMID- 26369255 TI - Only watching others making their experiences is insufficient to enhance adult neurogenesis and water maze performance in mice. AB - In the context of television consumption and its opportunity costs the question arises how far experiencing mere representations of the outer world would have the same neural and cognitive consequences than actively interacting with that environment. Here we demonstrate that physical interaction and direct exposition are essential for the beneficial effects of environmental enrichment. In our experiment, the mice living in a simple standard cage placed in the centre of a large enriched environment only indirectly experiencing the stimulus-rich surroundings (IND) did not display increased adult hippocampal neurogenesis. In contrast, the mice living in and directly experiencing the surrounding enriched environment (DIR) and mice living in a similar enriched cage containing an uninhabited inner cage (ENR) showed enhanced neurogenesis compared to mice in control conditions (CTR). Similarly, the beneficial effects of environmental enrichment on learning performance in the Morris Water maze depended on the direct interaction of the individual with the enrichment. In contrast, indirectly experiencing a stimulus-rich environment failed to improve memory functions indicating that direct interaction and activity within the stimulus-rich environment are necessary to induce structural and functional changes in the hippocampus. PMID- 26369256 TI - Identification and profiling of microRNAs associated with white and black plumage pigmentation in the white and black feather bulbs of ducks by RNA sequencing. AB - MicroRNAs (miRNAs) play important roles in many biological processes by regulating gene expression at the post-transcriptional level. However, the mechanism by which specific miRNAs may regulate plumage pigmentation has remained largely elusive. In this study, we sequenced miRNAs using Solexa sequencing and then performed a detailed analysis of their expression profiles between the black and white feather bulbs of ducks from Cui Hei, Kaiya, Liancheng pure breeds and a Kaiya-Liancheng F2 population. mirdeep2 software identified 121 conserved and eight novel miRNAs. Five differentially expressed miRNAs between the two tissues types were also identified by degseq software. Notably, miR-204 was predominantly expressed in black feather bulbs. To further validate the sequencing data, we applied stem-loop quantitative PCR of ten known miRNAs based on the identified sequences. Furthermore, in exploring the temporal expression pattern of miR-204, we performed profiling in nine duck tissues. The targets of these miRNAs were predicted using a PITA algorithm and were later grouped based on Gene Ontology and KEGG pathway analysis using the DAVID website. The melanogenesis pathway was among the identified signalling pathways, implying key roles of these miRNAs in plumage pigmentation. Expression analysis of the target genes in the melanogenesis pathways was also performed. This study provides the foundation for subsequent studies on the prospective practical role for such miRNAs in post transcriptional gene regulation linked to plumage pigmentation. PMID- 26369257 TI - NUCB2 gene polymorphism and its relationship with nesfatin-1 levels in polycystic ovary syndrome. AB - Nesfatin-1, encoded by the nucleobindin-2 (NUCB2) gene, is an anorexigenic protein related to energy metabolism, obesity, and insulin resistance. The aim of this study was to evaluate NUCB2 gene polymorphism (rs757081) and its association with serum levels of nesfatin-1 in obese and non-obese women with polycystic ovary syndrome (PCOS). In the study population, we analyzed 60 patients with PCOS and 26 age-matched healthy women as controls. The patients with PCOS were divided into two groups based on body mass index (BMI): obese group (n = 28) or non-obese group (n = 32). NUCB2 was genotyped using the polymerase chain reaction restriction (PCR) technique. Serum nesfatin-1 level was measured by enzyme-linked immunosorbent assay (ELISA). Nesfatin-1 levels in the obese PCOS group were significantly lower than those in the non-obese PCOS and control groups (p < 0.001). There was no statistically significant difference in the distribution of NUCB2 genotypes among the groups (p > 0.05), whereas nesfatin-1 levels in the CC and CG genotypes were lower than those in the GG genotype. Nesfatin-1 decreases in PCOS, especially in obese women, and is negatively correlated with cardiometabolic risk factors. Although genotype disturbances of NUCB2 were similar among the groups, CC and CG genotypes accompanied lower nesfatin-1 levels. C allele of NUCB2 gene polymorphism and nesfatin-1 may play a role in the pathophysiology of PCOS. PMID- 26369258 TI - Therapeutic uses of FGFs. AB - Fibroblast growth factors and their receptors regulate a wide range of biological functions from developmental processes during embryogenesis to diverse physiological roles in the adult state, including the regulation of angiogenesis, wound healing, and metabolism. Genetic defects, or dysregulated FGF signaling, result in a variety of human conditions, which in turn provides a myriad of potential opportunities for FGF-targeted therapies to treat diseases such as cancer, impaired wound healing, metabolic syndrome, chronic kidney disease, and cardiovascular diseases. This review summarizes some of these approaches, focusing on recombinant FGFs or FGFR fragments, small molecule inhibitors, agonistic and antagonistic antibodies, and nucleic acid based therapeutics. PMID- 26369259 TI - An Adverse Implication of Radiation Therapy for Implant-Retained Maxillofacial Prostheses. AB - We report the 19-year postoperative course of a patient whose maxillary defect was reconstructed with maxillofacial implant-retained facial prostheses. The patient received 60 Gy of radiation therapy. Adjunctive hyperbaric oxygen therapy was administered and four 4.0-mm long maxillofacial implants were inserted. Four years and 6 months after insertion surgery, two of the four implants were lost and the others showed bone regression in the surrounding bone. All implants were replaced with Epitec System maxillofacial implants placed in non-irradiated bone. Eleven years and 6 months after replacement, the Epitec System has been maintaining good and firm osseointegration. Appropriate selection of implant sites and no history of radiation therapy are keys to successful implant reconstruction. However, adjunctive hyperbaric oxygen therapy is believed to be effective, osseointegrated implant should be inserted at a point appropriately distant from an irradiated lesion. PMID- 26369260 TI - Pulmonary Artery Aneurysm/Pseudoaneurysm, a Delayed Complication of Lung Abscess: A Case Report. AB - BACKGROUND: Massive hemoptysis mostly arises from the bronchial arteries; however, bleeding can also occur from a lesion in injured pulmonary arteries, such as pulmonary artery aneurysm/pseudoaneurysm (PAA/PAP), during pulmonary infection. CASE REPORT: A 66-year-old man was admitted with a diagnosis of lung abscess in the right lower lobe that was complicated with pyothorax. Intravenous administration of antibiotics and thoracic drainage successfully controlled the infection and inflammation until day 16, when the patient began to exhibit hemoptysis and bloody pleural effusion. Enhanced computed tomography (CT) with multi-planer reconstruction (MPR) images showed a highly enhanced mass inside the abscess fed by the pulmonary artery, suggesting PAA/PAP. Pulmonary angiography confirmed PAA/PAP, and embolization with coils successfully stopped both the bleeding into the sputum and pleural effusion, with a collapsed aneurysm visible on chest CT scan. CONCLUSION: Clinicians should consider the possibility of PAA/PAP in the differential diagnosis of hemoptysis during the treatment of patients with lung abscess. MPR CT is helpful for the diagnosis of PAA/PAP and its feeding vessels. PMID- 26369261 TI - A Long Surviving Case of Multiple Early Stage Primary Malignant Melanoma of the Esophagus and a Review of the Literature. AB - We report a 75 year old man in whom primary malignant melanoma of the esophagus (PMME) was detected on an upper gastrointestinal radiographic contrast study and upper gastrointestinal endoscopy during a regular medical checkup. An extensive black lesion with a 1.5 x 1.0 cm protrusion and diffuse 1 cm flat lesions were recognized. The results of radical surgery were PMME pT1a-MM ly1 v0 pN0 (0/86) multiple lesions (+). Adjuvant chemotherapy was not employed and he has survived almost 7 years with no evidence of recurrence. PMME is a very rare lesion and in the PubMed database only 85 cases in 73 reports accumulated in a 10 year period from 2005 to 2014. Until 2014 a total of 369 cases were reported. In the ICHUSHI database (a domestic medical literature database service provided by the NPO Japan Medical Abstracts Society), 65 lesions in 62 cases were reported in the same period. Also until 2014, 301 cases were reported. At present, surgery is the first choice of treatment for PMME extending to the submucosa or deeper, but with developments in molecular targeting agents, PMME is thought to likely become an expanded indication of this technique. PMID- 26369262 TI - Resection of a Submucosal Tumor-Like Superficial Carcinoma in Middle Thoracic Esophagus Concomitant with Mucosal Adenocarcinoma and Submucosal Squamous Cell Carcinoma: A Case Report and Review of Literature. AB - A 67-year-old man was pointed out mucosal irregularity on health check-up and was referred to our institution. Diagnostic examinations were performed and an aggregated type 0-IIa lesion having 3 small protrusions was recognized in the middle thoracic esophagus. Endoscopic biopsy led to diagnosis of esophageal cancer concomitant with adenocarcinoma and squamous cell carcinoma. Thoracic esophagectomy with 3-fields lymph node dissection was performed via a right thoracoabdominal approach and reconstructed with stomach roll. Three submucosal tumors like small protrusions were recognized in resected specimen. One of them was well differentiated tubular adenocarcinoma which occupied in mucosal layer. The other two were moderately differentiated squamous cell carcinoma. They existed very near but no connection was recognized by serial section. The adenocarcinoma existing in middle esophagus is very rare. Almost all of them were submucosal or advanced cancers. When we searched with the ICHUSHI database (a domestic medical literature database service provided by the NPO Japan Medical Abstracts Society) and the PubMed database, there was no report of mucosal adenocarcinoma occurred in middle thoracic esophagus in the past 10 years. Then this report was thought to be the first report of mucosal adenocarcinoma in middle thoracic esophagus in the world. PMID- 26369263 TI - A Case of Colon Cancer Associated with Ulcerative Colitis: Evaluation Using CT Colonography. AB - A 29-year-old female with ulcerative colitis was found to have advanced sigmoid colon cancer on colonoscopy. Computed tomography (CT) was performed after colonoscopy for the evaluation of metastasis. CT colonography (CTC) could be understood adding carbon dioxide because of soon after colonoscopic examination. Images of CTC were evaluated by two- and three-dimensional images including virtual endoscopic, virtual colon dissection and air images, and then compared with conventional endoscopic images. Virtual endoscopic images of flat elevated cancer with shallow ulcer were similar to those findings by conventional endoscopy. This lesion could be depicted by computer-aided detection. PMID- 26369264 TI - Pyogenic Granuloma: A Retrospective 10-year Analysis of 82 Cases. AB - OBJECTIVE: Pyogenic granuloma (PG) is a common acquired hemorrhagic benign vascular lesion of the skin and mucous membranes. Recently, PG was considered a capillary hemangioma and was renamed as lobular capillary hemangioma (LCH). A clinical retrospective analysis of PG cases in our institute over a period of 10 years was performed. METHODS: The study involved 82 cases of pathologically diagnosed PG managed and treated at the Plastic Surgery Department of Tokai University between 1995 and 2004. Individual data from charts were reviewed for age, gender, affected site, size of lesion, predisposing factors, and treatment. All lesions were treated surgically using an excision followed by suture, or shave excision followed by CO2 laser ablation. RESULTS: The overall male to female ratio was 1.5:1. In 28% of the total cases, a preceding lesion was evident prior to the occurrence of PG. The head and neck area were the most commonly affected sites (56%), followed by the upper limb (22%), trunk (16%), and lower limbs (6%). CO2 laser ablation was performed successfully in 24% of patients and resulted in no recurrences. CONCLUSION: Based on our results, we recommend surgical excision followed by CO2 laser ablation as the first-choice treatment for PGs. PMID- 26369265 TI - Combination of Laparoscopic and Endoscopic Approaches to Neoplasia with Non exposure Technique (CLEAN-NET) for GIST with Ulceration. AB - Combination of laparoscopic and endoscopic approaches to neoplasia with non exposure technique (CLEAN-NET) was developed to avoid intraoperative tumor dissemination. We report two cases of gastric gastrointestinal stromal tumor (GIST) with ulceration surgically treated with CLEAN-NET at our institution. The first case was a 55-year-old male with hematemesis. Gastric endoscopy revealed a gastric GIST with ulceration of the fornix. CLEAN-NET was performed with the insertion of five trocars and a liver retractor. The operative time was 202 min (including cholecystectomy), with a perioperative blood loss volume of 29 ml; the postoperative hospital stay duration was 8 days. The second case was a 66-year old male with a gastric submucosal tumor (SMT) with ulceration. CLEAN-NET was performed in a similar fashion to the first case. The operative time was 128 min, with a preoperative blood loss volume of 16 ml; the postoperative hospital stay duration was 9 days. In conclusion, CLEAN-NET was found to be safe and useful in the treatment of gastric GIST with ulceration. PMID- 26369266 TI - Solitary Fibrous Tumor of the Stomach Treated with Laparoscopic and Endoscopic Cooperative Surgery. AB - A 43-year-old Japanese woman with melena underwent an upper gastrointestinal endoscopy and was preoperatively diagnosed with sarcoma of the stomach. Physical examination revealed no abnormalities. Findings on the upper gastrointestinal endoscopy showed a pedunculated submucosal tumor measuring 17 mm in the antrum. An enhanced computed tomography showed wall thickening in the gastric antrum. The patient underwent a laparoscopic and endoscopic cooperative surgery (LECS) for wedge resection of the stomach. The excised tumor measured 27 * 20 * 15 mm in size. Histopathology showed spindle-shaped cells in the submucosal layer. Immunohistochemistry showed that the tumor was positive for CD34, bcl-2, and MIC 2. The final diagnosis was solitary fibrous tumor (SFT) of the stomach. The postoperative course was uneventful, and no evidence of recurrence was observed at the 8-month follow-up. We report a case of SFT arising from the stomach that was treated with wedge resection by LECS. PMID- 26369267 TI - Clinical Features of Non-clostridial Gas Gangrene and Risk Factors for In hospital Mortality. AB - OBJECTIVE: To examine the clinical features of patients with non-clostridial gas gangrene (NCGG) at our hospital and identify risk factors for in-hospital mortality. METHODS: This study included 24 patients with NCGG who were hospitalized in our medical facility from April 2005 to March 2015. The clinical features of NCGG were reviewed, and the characteristics of 6 patients who died in hospital and 18 who survived were compared to investigate risk factors. RESULTS: The median time from symptom onset to hospital arrival was 168 h. The causative agent was Klebsiella pneumoniae in 8.3% and mixed infection in 91.7%; 83.3% of patients had diabetes, and one patient had no obvious underlying disease. The site of infection was the neck in 4.2%, the thoracoabdominal wall and retroperitoneum in 12.5% each, the back in 33.3%, the buttocks in 25.0%, the perineum in 20.8%, and the extremities in 45.8%. Retroperitoneal infection, blood lactate >= 4.0 mmol/L, and Japanese Association for Acute Medicine disseminated intravascular coagulation (DIC) score >= 4 on emergency department (ED) arrival were significantly higher in non-survivors than in survivors. CONCLUSION: NCGG tends to develop in patients with diabetes, and in-hospital mortality rates are still high. Retroperitoneal infection, hyperlactatemia, and DIC on ED arrival are risk factors for in-hospital mortality. PMID- 26369268 TI - Autonomic function in reflex and non-reflex epilepsy--an exploratory study. AB - PURPOSE: Seizures are known to affect diverse areas of the Central Autonomic Network (CAN) resulting in varied autonomic symptoms. The objectives of the study were to characterize neuro-cardiac autonomic regulation in hot water epilepsy (HWE) with or without spontaneous seizure, and to analyze the effect of Carbamazepine (CBZ). METHODS: Seventy patients of HWE [42 drug-naive 'HWE only' and 28 'HWE with spontaneous complex partial seizure (CPS),' on CBZ] and 40 spontaneous CPS on CBZ were recruited after informed consent. Fifty healthy volunteers served as control. Conventional cardiac autonomic function tests, Heart Rate Variability (HRV), Blood Pressure Variability (BPV), and baroreflex sensitivity (BRS) were performed. RESULTS: Significant dysfunction was evidenced in most of the autonomic function parameters in all the epilepsy subgroups when compared with controls. Significant reduction in the parasympathetic activity in HWE patients was observed. Significant impairment of short-term fluctuation of blood pressure in 'HWE with spontaneous CPS' compared to 'healthy volunteers' was detected. Compared to 'HWE only', 'HWE with spontaneous CPS' showed impaired sympathovagal balance. The BRS were also altered in 'HWE with spontaneous CPS' compared to 'HWE only'. The comparison of 'spontaneous CPS' with 'HWE with spontaneous CPS' and 'HWE only' showed reduced parasympathetic and sympathetic activities. CONCLUSION: Both cardiovascular reflexes and autonomic cardiovascular regulation were altered in HWE, more so in 'HWE with spontaneous seizures'. Compared to those on CBZ, drug naive had severe effect on vagal tone and CBZ did not alter cardiac autonomic functions in reflex as well as in non-reflex epilepsies. PMID- 26369269 TI - Split liver transplantation: Report of right and left graft outcomes from a multicenter Argentinean group. AB - Grafts from split livers (SLs) constitute an accepted approach to expand the donor pool. Over the last 5 years, most Argentinean centers have shown significant interest in increasing the use of this technique. The purpose of this article is to describe and analyze the outcomes of right-side grafts (RSGs) and left-side grafts (LSGs) from a multicenter study. The multicenter retrospective study included data from 111 recipients of SL grafts from between January 1, 2009 and December 31, 2013. Incidence of surgical complications, patient and graft survival, and factors that affected RSG and LSG survival were analyzed. Grafts types were 57 LSG and 54 RSG. Median follow-up times for LSG and RSG were 46 and 42 months, respectively. The 36-month patient and graft survivals for LSG were 83% and 79%, respectively, and for RSG were 78% and 69%, respectively. Retransplantation rates for LSG and RSG were 3.5% and 11%, respectively. Arterial complications were the most common cause of early retransplantation (less than 12 months). Cold ischemia time (CIT) longer than 10 hours and the use of high-risk donors (age >= 40 years or body mass index >= 30 kg/m2 or >= 5 days intensive care unit stay) were independent factors for diminished graft survival in RSG. None of the analyzed variables were associated with worse graft survival in LSG. Biliary complications were the most frequent complications in both groups (57% in LSG and 33% in RSG). Partial grafts obtained from liver splitting are an excellent option for patients in need of liver transplantation and have the potential to alleviate the organ shortage. Adequate donor selection and reducing CIT are crucial for optimizing results. PMID- 26369270 TI - Copper-catalyzed C(sp(3))-H functionalization of ketones with vinyl azides: synthesis of substituted-1H-pyrroles. AB - Copper-catalyzed C(sp(3))-H functionalization of ketones with vinyl azides for the synthesis of substituted pyrroles has been developed. The method is a straightforward and efficient way to access a series of 2,3,5-trisubstituted-1H pyrroles in modest to excellent yields with broad functional group tolerance under mild conditions. PMID- 26369271 TI - Use of dienogest over 53 weeks for the treatment of endometriosis. AB - AIM: To evaluate the efficacy and adverse effects of Dienogest (DNG) over 53 weeks for the treatment of endometriosis. METHODS: DNG was administered to 75 patients with endometriosis over a period of 53 weeks. Medical charts were retrospectively examined on the efficacy and side effects. Reduction rates of ovarian chocolate cyst, adenomyosis and changes in serum estradiol and cancer antigen 125 concentration were measured. Adverse effects, patient evaluation of their symptoms and willingness to continue taking DNG were assessed by a questionnaire. RESULTS: The median duration of treatment was 87 weeks, with the longest follow-up duration being 120 weeks. Ovarian chocolate cysts were initially reduced; however, upon cessation of DNG treatment, an increase in size was observed. Adenomyosis lesions were reduced to some extent after 53 weeks of DNG treatment. In terms of adverse events, more than 60% (61.3%, 46/75) of patients experienced atypical genital bleeding. However, this did not prove to be a cause of discontinuation. We ceased DNG treatment in two cases because of lower abdominal pain and shoulder discomfort. CONCLUSIONS: Long term DNG treatment beyond one year for endometriosis proved to be effective and safe. Ovarian chocolate cysts were markedly reduced by short-term use of DNG, while a longer duration was required to reduce the size of adenomyosis. The decision regarding the choice of therapy lies with the individual clinician, considering a balance of efficacy with expense and adverse effects. PMID- 26369272 TI - Does boceprevir really increase the risk of skin eruptions during antihepatitis C treatment? PMID- 26369273 TI - Corrigendum. PMID- 26369274 TI - Evaluation of the injection pain with the use of DentalVibe injection system during supraperiosteal anaesthesia in children: a randomised clinical trial. AB - PURPOSE: The purpose of this study was to compare the use of a traditional syringe (TS) and the DentalVibe (DV) Injection Comfort System on the pain of needle insertion and injection of supraperiosteal (SP) anaesthesia into the mandibles and maxillas of children aged 6-12 years. METHODS: The study was a randomised, controlled, crossover clinical trial, comprising 60 children requiring an operative procedure with SP anaesthesia on both their mandibular and maxillary molars, bilaterally. One of the molars was treated with a TS, and the contralateral tooth was treated with the DV for both arches. On each visit, subjective and objective pain was evaluated using the Wong-Baker FACES Pain Rating Scale and the Face, Leg, Activity, Cry, Consolability Scale. Patients were asked which technique they preferred. The data were analysed using Wilcoxon signed-rank test, Spearman's correlation test, and Mann-Whitney U-test. RESULTS: No statistically significant differences were noted between TS and DV for pain during injection and needle insertion for supraperiosteal anaesthesia in either the maxillary and mandibular operative procedures. CONCLUSIONS: Children experienced similar pain during SP anaesthesia administered with a TS and the DV, regardless of gender and jaw differences. DV was less preferred over the traditional procedure in children. PMID- 26369275 TI - Simultaneous evaluation of plasma membrane integrity, acrosomal integrity, and mitochondrial membrane potential in bovine spermatozoa by flow cytometry. AB - The present study aimed to develop an objective evaluation procedure to estimate the plasma membrane integrity, acrosomal integrity, and mitochondrial membrane potential of bull spermatozoa simultaneously by flow cytometry. Firstly, we used frozen-thawed semen mixed with 0, 25, 50, 75 or 100% dead spermatozoa. Semen was stained using three staining solutions: SYBR-14, propidium iodide (PI), and phycoerythrin-conjugated peanut agglutinin (PE-PNA), for the evaluation of plasma membrane integrity and acrosomal integrity. Then, characteristics evaluated by flow cytometry and by fluorescence microscopy were compared. Characteristics of spermatozoa (viability and acrosomal integrity) evaluated by flow cytometry and by fluorescence microscopy were found to be similar. Secondly, we attempted to evaluate the plasma membrane integrity, acrosomal integrity, and also mitochondrial membrane potential of spermatozoa by flow cytometry using conventional staining with three dyes (SYBR-14, PI, and PE-PNA) combined with MitoTracker Deep Red (MTDR) staining (quadruple staining). The spermatozoon characteristics evaluated by flow cytometry using quadruple staining were then compared with those of staining using SYBR-14, PI, and PE-PNA and staining using SYBR-14 and MTDR. There were no significant differences in all characteristics (viability, acrosomal integrity, and mitochondrial membrane potential) evaluated by quadruple staining and the other procedures. In conclusion, quadruple staining using SYBR-14, PI, PE-PNA, and MTDR for flow cytometry can be used to evaluate the plasma membrane integrity, acrosomal integrity, and mitochondrial membrane potential of bovine spermatozoa simultaneously. PMID- 26369276 TI - Rapid estimation of the biochemical methane potential of plant biomasses using Fourier transform mid-infrared photoacoustic spectroscopy. AB - Biochemical methane potential (BMP) is a very important characteristic of a given feedstock for optimisation of its use in biogas production. However, the long digestion time needed to determine BMP is the main limitation for the use of this assay during the operation of anaerobic digesters to produce biogas. Fourier transform mid-infrared photoacoustic spectroscopy (FTIR-PAS) was used to predict the BMP of 87 plant biomasses. The developed calibration model was able to explain 81% of the variance in the measured BMP of a selected test set with a root mean square error (RMSE) of 40NLCH4kg(-1) of volatile solids (VS) and a ratio of performance to deviation (RPD) of 2.38. The interpretation of the regression coefficients used in the calibration revealed a positive correlation of BMP with easily degradable compounds (amorphous cellulose, hemicellulose and aliphatic compounds) and a negative correlation with inhibitors of cellulose hydrolysis (lignin, hemicellulose). PMID- 26369277 TI - High-rate biological denitrification in the cyclic rotating-bed biological reactor: Effect of COD/NO3(-), nitrate concentration and salinity and the phylogenetic analysis of denitrifiers. AB - The effects of COD/NO3(-) ratio, nitrate concentration and salinity was tested on the performance of the CRBR in denitrification with catechol as carbon source. The maximum nitrate reduction attained at COD/NO3(-) ratio of 1. The CRBR operated at optimum COD/NO3(-) ratio could completely denitrify the nitrate at inlet concentration up to 1250mg/L without nitrite accumulation. The maximum denitrification rate in the CRBR was 3.56kgNO3(-)/m(3)d with a nitrate reduction efficiency of 99% when the bioreactor was operated at inlet nitrate loading rate of 3.6kgNO3(-)/m(3)d. The denitrification performance of the CRBR was not affected significantly by NaCl concentrations up to 20g/L. 16S rRNA fragment and phylogenetic analysis identified Pseudomonas resinovorans, Stenotrophomonas maltophilia and Bacillus cereus as the most abundant denitrifiers in biomass. Accordingly, the CRBR is a high-rate bioreactor and appropriate technology for treatment of nitrate-laden industrial wastewaters containing phenolic compounds and salinity. PMID- 26369278 TI - Formation of bacterial aerobic granules: Role of propionate. AB - Propionate presents as one of the major volatile fatty acids in municipal wastewaters, which are not readily degraded as acetate by microorganisms. This study cultivated aerobic granules from column reactors with acetate, acetate/propionate mix (3:1 and 1:3) and propionate as carbon sources and noted that propionate-rich feed would delay granulation, but could generate granules with high structural strength. Propionate feed enriched strains fractionated into the hydrophobic phase, Sphaerotilus sp., Sphingomonadaceae and Thauera sp., in granules and altered hydrophobicity of Thauera sp. and Zoogloea sp. The enriched strains could secret high quantities of cyclic-di-diguanylate to increase production of extracellular polymeric substances (EPS). The hydrophobic cell surface and increased EPS quantity led to integrated propionate-fed granules. Feed with high propionate concentration is proposed as promising way to cultivate strong aerobic granules for practical use. PMID- 26369280 TI - Reaction Dynamics of Proton-Coupled Electron Transfer from Reduced ZnO Nanocrystals. AB - The creation of systems that efficiently interconvert chemical and electrical energies will be aided by understanding proton-coupled electron transfers at solution-semiconductor interfaces. Steps in developing that understanding are described here through kinetic studies of reactions of photoreduced colloidal zinc oxide (ZnO) nanocrystals (NCs) with the nitroxyl radical TEMPO. These reactions proceed by proton-coupled electron transfer (PCET) to give the hydroxylamine TEMPOH. They occur on the submillisecond to seconds time scale, as monitored by stopped-flow optical spectroscopy. Under conditions of excess TEMPO, the reactions are multiexponential in character. One of the contributors to this multiexponential kinetics may be a distribution of reactive proton sites. A graphical overlay method shows the reaction to be first order in [TEMPO]. Different electron concentrations in otherwise identical NC samples were achieved by three different methods: differing photolysis times, premixing with an unphotolyzed sample, or prereaction with TEMPO. The reaction velocities were consistently higher for NCs with higher numbers of electrons. For instance, NCs with an average of 2.6 e(-)/NC reacted faster than otherwise identical samples containing <=1 e(-)/NC. Surprisingly, NC samples with the same average number of electrons but prepared in different ways often had different reaction profiles. These results show that properties beyond electron content determine PCET reactivity of the particles. PMID- 26369279 TI - Evaluation of several flocculants for flocculating microalgae. AB - Flocculation of microalgae with chitosan, polyacrylamide, Al2(SO4)3, NaOH and HNO3 was evaluated. Their flocculation efficiencies and optimal dosages were discussed. The effects of the flocculants on cells viability were also investigated and the cells were found to be intact during the flocculation process. Moreover, the effects of flocculants on the extractions were evaluated. Lipid content after flocculants treatments showed no significant differences. Carbohydrate content was lower but protein content was higher after NaOH treatment than those after other treatments. Furthermore, the five flocculated media maintained approximate growth yields to that of the fresh medium in microalgal cultivation, indicating the five flocculated media could be recycled, thereby reducing the cost of biodiesel production from microalgae. Finally, economic comparison of the flocculants was made and the cost of using HNO3, including flocculating cells and recycling medium, was found to be the lowest. PMID- 26369281 TI - Morphogenesis of the inner ear at different stages of normal human development. AB - This study examined the external morphology and morphometry of the human embryonic inner ear membranous labyrinth and documented its three-dimensional position in the developing embryo using phase-contrast X-ray computed tomography and magnetic resonance imaging. A total of 27 samples between Carnegie stage (CS) 17 and the postembryonic phase during trimester 1 (approximately 6-10 weeks after fertilization) were included. The otic vesicle elongated along the dorso-ventral axis and differentiated into the end lymphatic appendage and cochlear duct (CD) at CS 17. The spiral course of the CD began at CS18, with anterior and posterior semicircular ducts (SDs) forming prominent circles with a common crus. The spiral course of the CD comprised more than two turns at the postembryonic phase, at which time the height of the CD was evident. A linear increase was observed in the length of anterior, posterior, and lateral SDs, in that order, and the length of the CD increased exponentially over the course of development. Bending in the medial direction was observed between the cochlear and vestibular parts from the latero-caudal view, with the angle decreasing during development. The position of the inner ear was stable throughout the period of observation on the lateral to ventral side of the rhombencephalon, caudal to the pontine flexure, and adjacent to the auditory ganglia. The plane of the lateral semicircular canal was approximately 8.0 degrees -14.6 degrees with respect to the cranial caudal (z )axis, indicating that the orientation of the inner ear changes during growth to adulthood. PMID- 26369282 TI - Elevated corticospinal excitability in patellar tendinopathy compared with other anterior knee pain or no pain. AB - Anterior knee pain (AKP) is a frequent clinical presentation in jumping athletes and may be aggravated by sustained sitting, stair use, and loading of the quadriceps. Corticospinal activation of the quadriceps in athletes with AKP has not yet been investigated, but is important in guiding efficacious treatment. This cross-sectional study assessed corticospinal excitability (CSE) of the quadriceps in jumping athletes using transcranial magnetic stimulation (TMS). Groups consisted of Control (no knee pain); patellar tendinopathy (PT) [localized inferior pole pain on single-leg decline squat (SLDS)]; and other AKP (nonlocalized pain around the patella). SLDS (numerical score of pain 0-10), Victorian Institute of Sport Assessment Patellar tendon (VISA-P), maximal voluntary isometric contraction (MVIC), active motor threshold (AMT), CSE, and Mmax were tested. Twenty nine athletes participated; control n = 8, PT n = 11, AKP n = 10. There were no group differences in age (P = 0.23), body mass index (P = 0.16), MVIC (P = 0.38) or weekly activity (P = 0.22). PT had elevated CSE compared with controls and other AKP (P < 0.001), but no differences were detected between AKP and controls (P = 0.47). CSE appears to be greater in PT than controls and other AKP. An improved understanding of the corticospinal responses in different sources of knee pain may direct better treatment approaches. PMID- 26369283 TI - Mcm10 is required for oogenesis and early embryogenesis in Drosophila. AB - Efficient replication of the genome and the establishment of endogenous chromatin states are processes that are essential to eukaryotic life. It is well documented that Mcm10 is intimately linked to both of these important biological processes; therefore, it is not surprising that Mcm10 is commonly misregulated in many human cancers. Most of the research regarding the biological roles of Mcm10 has been performed in single-cell or cell-free in-vitro systems. Though these systems are informative, they are unable to provide information on the cell-specific function of Mcm10 in the context of the tissue and organ systems that comprise multicellular eukaryotes. We therefore sought to identify the potential biological functions of Mcm10 in the context of a complex multicellular organism by continuing our analysis in Drosophila using three novel hypomorphic alleles. Observation of embryonic nuclear morphology and quantification of embryo hatch rates reveal that maternal loading of Mcm10 is required for embryonic nuclear stability, and suggest a role for Mcm10 post zygotic transition. Contrary to the essential nature of Mcm10 depicted in the literature, it does not appear to be required for adult viability in Drosophila if embryonic requirements are met. Although not required for adult somatic viability, analysis of fecundity and ovarian morphology in mutant females suggest that Mcm10 plays a role in maintenance of the female germline. Taken together, our results demonstrate critical roles for Mcm10 during early embryogenesis, and mark the first data linking Mcm10 to female specific reproduction in multicellular eukaryotes. PMID- 26369284 TI - A randomised controlled trial of high vs low volume initiation and rapid vs slow advancement of milk feeds in infants with birthweights <= 1000 g in a resource limited setting. AB - BACKGROUND: Optimal feeding regimens for infants <= 1000 g have not been established and are a global healthcare concern. AIMS AND OBJECTIVES: A controlled trial to establish the safety and efficacy of high vs low volume initiation and rapid vs slow advancement of milk feeds in a resource-limited setting was undertaken. METHODS: Infants <= 1000 g birthweight were randomised to one of four arms, either low (4 ml/kg/day) or high (24 ml/kg/day) initiation and either slow (24 ml/kg/day) or rapid (36 ml/kg/day) advancement of exclusive feeds of human milk (mother's or donor) until a weight of 1200 g was reached. After this point, formula was used to supplement insufficient mother's milk. The primary outcome was time to reach 1500 g. RESULTS: infants were recruited (51: low/slow; 47: low/rapid; 52: high/slow; 50: high/rapid). Infants on rapid advancement regimens reached 1500 g most rapidly (hazard ratio 1.48, 95% CI 1.05 2.09, P=0.03). The rapid advancement groups also regained birthweight more rapidly (hazard ratio 1.77, 95% CI 1.26-2.50, P=0.001). There was no apparent effect of high vs low initiation volumes but there was some evidence of interaction between interventions. There were no significant differences in other secondary outcomes, including necrotising enterocolitis, feed intolerance and late-onset sepsis. CONCLUSIONS: In this small pilot study, higher initiation feed volumes and larger daily increments appeared to be well tolerated and resulted in more rapid early weight gain. These data provide justification for a larger study in resource-limited settings to address mortality, necrotising enterocolitis and other important outcomes. PMID- 26369286 TI - miR-124, -128, and -137 Orchestrate Neural Differentiation by Acting on Overlapping Gene Sets Containing a Highly Connected Transcription Factor Network. AB - The ventricular-subventricular zone harbors neural stem cells (NSCs) that can differentiate into neurons, astrocytes, and oligodendrocytes. This process requires loss of stem cell properties and gain of characteristics associated with differentiated cells. miRNAs function as important drivers of this transition; miR-124, -128, and -137 are among the most relevant ones and have been shown to share commonalities and act as proneurogenic regulators. We conducted biological and genomic analyses to dissect their target repertoire during neurogenesis and tested the hypothesis that they act cooperatively to promote differentiation. To map their target genes, we transfected NSCs with antagomiRs and analyzed differences in their mRNA profile throughout differentiation with respect to controls. This strategy led to the identification of 910 targets for miR-124, 216 for miR-128, and 652 for miR-137. The target sets show extensive overlap. Inspection by gene ontology and network analysis indicated that transcription factors are a major component of these miRNAs target sets. Moreover, several of these transcription factors form a highly interconnected network. Sp1 was determined to be the main node of this network and was further investigated. Our data suggest that miR-124, -128, and -137 act synergistically to regulate Sp1 expression. Sp1 levels are dramatically reduced as cells differentiate and silencing of its expression reduced neuronal production and affected NSC viability and proliferation. In summary, our results show that miRNAs can act cooperatively and synergistically to regulate complex biological processes like neurogenesis and that transcription factors are heavily targeted to branch out their regulatory effect. PMID- 26369285 TI - The TRAF-interacting protein (TRAIP) is a novel E2F target with peak expression in mitosis. AB - The TRAF-interacting protein (TRAIP) is an E3 ubiquitin ligase required for cell proliferation. TRAIP mRNA is downregulated in human keratinocytes after inhibition of the PI3K/AKT/mTOR signaling. Since E2F transcription factors are downstream of PI3K/AKT/mTOR we investigated whether they regulate TRAIP expression. E2F1 expression significantly increased the TRAIP mRNA level in HeLa cells. Reporter assays with the 1400 bp 5'-upstream promoter in HeLa cells and human keratinocytes showed that E2F1-, E2F2- and E2F4-induced upregulation of TRAIP expression is mediated by 168 bp upstream of the translation start site. Mutating the E2F binding site within this fragment reduced the E2F1- and E2F2 dependent promoter activities and protein-DNA complex formation in gel shift assays. Abundance of TRAIP mRNA and protein was regulated by the cell cycle with a peak in G2/M. Expression of GFP and TRAIP-GFP demonstrated that TRAIP-GFP protein has a lower steady-state concentration than GFP despite similar mRNA levels. Cycloheximide inhibition experiments indicated that the TRAIP protein has a half-life of around four hours. Therefore, the combination of cell cycle dependent transcription of the TRAIP gene by E2F and rapid protein degradation leads to cell cycle-dependent expression with a maximum in G2/M. These findings suggest that TRAIP has important functions in mitosis and tumorigenesis. PMID- 26369287 TI - The fatty acid elongase Bond is essential for Drosophila sex pheromone synthesis and male fertility. AB - Insects use a spectacular variety of chemical signals to guide their social behaviours. How such chemical diversity arises is a long-standing problem in evolutionary biology. Here we describe the contribution of the fatty acid elongase Bond to both pheromone diversity and male fertility in Drosophila. Genetic manipulation and mass spectrometry analysis reveal that the loss of bond eliminates the male sex pheromone (3R,11Z,19Z)-3-acetoxy-11,19-octacosadien-1-ol (CH503). Unexpectedly, silencing bond expression severely suppresses male fertility and the fertility of conspecific rivals. These deficits are rescued on ectopic expression of bond in the male reproductive system. A comparative analysis across six Drosophila species shows that the gain of a novel transcription initiation site is correlated with bond expression in the ejaculatory bulb, a primary site of male pheromone production. Taken together, these results indicate that modification of cis-regulatory elements and subsequent changes in gene expression pattern is one mechanism by which pheromone diversity arises. PMID- 26369288 TI - Rituximab, a new treatment for difficult-to-treat chronic erythema multiforme major? Five cases. AB - BACKGROUND: Erythema multiforme major (EMM) is an inflammatory disease affecting skin and mucosae, often triggered by infection with Herpes simplex virus. Some patients have a chronic disease associated with antidesmoplakin autoantibodies, but the pathophysiology remains to be elucidated. First-line treatment is antiviral therapy. With treatment failure or in patients without herpes-triggered disease, thalidomide is effective but has neurological side-effects. Alternatives (dapsone, immunosuppressant agents) are not codified. For many patients, systemic steroids use is chronic. The immunosuppressant drug rituximab (RTX) may be effective. OBJECTIVES: We report five cases of severe chronic EMM treated with rituximab (RTX). METHODS: Five patients with severe chronic EMM for 9-20 years received RTX after failure or side-effects of several treatments, especially antiviral therapy and thalidomide. All had chronic use of steroids. Four patients had antidesmoplakin autoantibodies. RESULTS: Four patients experienced complete or quasi-complete remission of EMM with withdrawal of steroids and one patient partial remission, for 3-11 months. Disease relapsed in all patients, and three received a second cycle of RTX with shorter duration of efficacy. Two patients received a third cycle, one without efficacy. CONCLUSION: The use of RTX for many autoimmune diseases, especially pemphigus, is increasing. Chronic EMM, especially EMM associated to antidesmoplakin autoantibodies, is an inflammatory disease in which the role of B cells is not well understood. However, we report a favourable benefit of RTX treatment for months in five patients with severe disease. RTX could be a therapeutic option in severe, difficult-to-treat EMM. PMID- 26369289 TI - Evaluation of spectroscopic properties of Er(3+)/Yb(3+)/Pr(3+): SrGdGa3O7 crystal for use in mid-infrared lasers. AB - Er(3+)/Yb(3+)/Pr(3+): SrGdGa3O7 crystal was firstly grown by Czochralski method. Detailed spectroscopic analyses of Er(3+)/Yb(3+)/Pr(3+): SrGdGa3O7 were carried out. Besides better absorption characteristic, the spectra of Er(3+)/Yb(3+)/Pr(3+): SrGdGa3O7 show weaker up-conversion and near-infrared emissions as well as superior mid-infrared emission in comparison to Er(3+): SrGdGa3O7 and Er(3+)/Yb(3+): SrGdGa3O7 crystals. Furthermore, the self termination effect for Er(3+) 2.7 MUm laser is suppressed successfully because the fluorescence lifetime of the (4)I(13/2) lower level of Er(3+) decreases markedly while that of the upper (4)I(11/2) level changes slightly in Er(3+)/Yb(3+)/Pr(3+): SrGdGa3O7 crystal. The sensitization effect of Yb(3+) and deactivation effect of Pr(3+) ions as well as the energy transfer mechanism in Er(3+)/Yb(3+)/Pr(3+): SrGdGa3O7 crystal were also studied in this work. The introduction of Yb(3+) and Pr(3+) is favorable for achieving an enhanced 2.7 MUm emission in Er(3+)/Yb(3+)/Pr(3+): SrGdGa3O7 crystal which can act as a promising candidate for mid-infrared lasers. PMID- 26369290 TI - Detection of novel kobu-like viruses in Japanese black cattle in Japan. AB - During surveillance for bovine diarrhea of unknown causes in Japanese black cattle in Kagoshima Prefecture, Japan, we found two types of novel kobu-like viruses in fecal samples of calves. Sequence analyses revealed that they had L protein and 2A protein with H-box/NC sequence motif, which are present in kobuviruses. Phylogenetic analysis revealed that they were related to kobuviruses; however, they clustered apart from other kobuviruses. In the prevalence study of two types of novel kobu-like viruses, 16.9% and 10.4% prevalence of these viruses were observed in the feces of diarrheal calves in this area. PMID- 26369291 TI - Anatomical variation of arterial supply to the rabbit spleen. AB - The rabbit, which is widely used as an experimental animal and is also popular as a companion animal, has a flat and elongated spleen with the longitudinal hilus running along its visceral surface. The spleen receives via the hilus an arterial supply that is essential for splenic nutrition and normal functioning. However, the distribution and variation of the arteries to the spleen have not been studied in detail. This study investigated anatomical variations of splenic arterial supply in 33 New Zealand White rabbits with a colored latex injection into arteries. We also examined whether the length of the spleen correlated with the number of the splenic branches of the splenic artery. The splenic artery always arose as the first independent branch of the celiac artery and ran along the splenic hilus to usually provide 6 (range, 3 to 10) splenic branches to the spleen. There was a moderate correlation (R=0.6) between the number of splenic branches and the longitudinal length of the spleen. The splenic branches often arose as a trunk or trunks in common with short gastric arteries. The number of common trunk(s) was usually 1 (range, 0 to 4). The data showed that the pattern and number of arterial branches to the spleen varied according to the individual animal, suggesting that such variations should be considered when performing experimental and veterinary surgical treatments in rabbits. PMID- 26369292 TI - More effective induction of anesthesia using midazolam-butorphanol-ketamine sevoflurane compared with ketamine-sevoflurane in the common marmoset monkey (Callithrix jacchus). AB - The common marmoset has been increasingly used for research in the biomedical field; however, there is little information available regarding effective methods of anesthesia in this species. This study retrospectively analyzed 2 regimens of anesthesia induction: intramuscular injection of ketamine followed by inhalation of 5% sevoflurane, and intramuscular injection of midazolam, butorphanol and ketamine followed by inhalation of 5% sevoflurane. Anesthetic depth did not reach the surgical anesthesia stage in 7 out of 99 animals receiving the former regimen, whereas there were only 2 such animals out of 273 receiving the latter regimen. The latter regimen, when followed by maintenance anesthesia with 3% sevoflurane inhalation, was successfully used in various nociceptive procedures. These results indicate that the injection of a combination of midazolam, butorphanol and ketamine followed by inhalation of a high concentration of sevoflurane is effective for anesthesia induction in marmosets. PMID- 26369293 TI - The functional-morphological adaptive strategy of digestive organs of decapodiform cephalopods. AB - The digestive organs in decapodiform cephalopod species morphologically vary by individual lifestyle. We examined the following six species of adult decapodiformes cephalopods representing different habitats: Todarodes pacificus, Loligo bleekeri, Loligo edulis, Watasenia scintillans (pelagic), Sepia lycidas and Euprymna morsei (benthic). L. bleekeri and L. edulis possess a bursiform cecal sac connected to the cecum. Pelagic species have a single digestive gland smaller than in benthic species. T. pacificus has an oval digestive gland larger than that of L. bleekeri and L. edulis, which possess withered-looking and smaller digestive glands. In contrast, the digestive glands in benthic species are paired. S. lycidas and E. morsei have well-developed and larger digestive glands than those of the pelagic species. Well-developed digestive duct appendages are found in benthic species. In qualification of the mass of digestive organs, pelagic species have smaller stomachs, digestive glands and digestive ducts' appendages than benthic species. Because pelagic species need to swim, they may possess smaller stomachs and larger cecums for more rapid digestion. A smaller digestive gland may have the advantage of reducing the body weight in pelagic species for rapid swimming. In contrast, since benthic species require a longer time for digestion than pelagic species, they compact more food in their stomachs and absorb nutrients via more organs, such as the digestive grand and digestive duct appendages, in addition to cecum. PMID- 26369294 TI - Prevalence and incidence of erythrovirus B19 infection in children with sickle cell disease: The impact of viral infection in acute clinical events. AB - B19V infection is common during childhood. It is self-limited in healthy individuals, but is often associated with transient aplastic crisis in children with sickle cell disease. The aim of this study was to estimate the prevalence and incidence of B19V infection in children with sickle cell disease screened by the Newborn Screening Program of Minas Gerais, Brazil, and followed-up at Fundacao Hemominas. Serum or plasma samples from 278 patients were tested for anti-B19V IgG and IgM using commercial ELISA and for viral DNA using in-house real-time PCR assays; 127 negative-children were retested about 1 year later. The median age of children at first testing was 5.9 years (0.8-12.3). The estimated prevalence of B19V was 29.5 % (95%CI 24.1-34.9 %). The incidence of B19V in those 127 negative-children was 18.2 cases/100 patient-years. All DNA-positive samples were identified as genotype 1, except one sample, in which both genotypes 1 and 3 were identified. It was observed that the higher the child's age, the higher the probability of B19V infection. The analysis of clinical and hematological data showed a significant association of B19V infection with transient aplastic crisis and acute splenic sequestration, higher frequency of transfusions, and higher rate of hospitalization, but not with acute chest syndrome or stroke. These results emphasize the impact of B19V infection on the course of sickle cell disease. Strategies to prevent and monitor B19V infection in children with sickle cell disease should be considered to diminish its morbidity in this susceptible population. PMID- 26369295 TI - Yellow and orange in cutaneous lesions: clinical and dermoscopic data. AB - Colour of the lesions is clue for the clinical and dermoscopic diagnosis. Nevertheless, we have detected in the literature an uneven relevance of the colours as a diagnostic criterion. Thus, while red, brown and blue have taken important role in dermoscopic descriptions, other like yellow and orange have been given much less importance. This article reviews those lesions in which the yellow and orange colours have been considered constitutive or essential for diagnosis, and on the other hand it emphasizes the entities in which may appear these colours and are not well reflected in the literature. We believe that organize all this information will help us in a better understanding of these pathologies. PMID- 26369296 TI - The use of growth factors, CD34(+) cells and fibrin for the management of chronic venous ulcers. AB - Chronic venous ulceration represents a very common event. Current standard treatment includes local wound care with the application of compression. We report the effects of platelet-rich plasma in patients with chronic venous ulcers, which is able to stimulate fibroblasts, macrophages and mesenchymal cells and growth factors in order to achieve re-epithelialisation and neovascularisation within the microenviroment of the wound. We also documented the efficacy of this method as the sole treatment without surgical procedures. PMID- 26369297 TI - The Role of Cesium Cation in Controlling Interphasial Chemistry on Graphite Anode in Propylene Carbonate-Rich Electrolytes. AB - Despite the potential advantages it brings, such as wider liquid range and lower cost, propylene carbonate (PC) is seldom used in lithium-ion batteries because of its sustained cointercalation into the graphene structure and the eventual graphite exfoliation. Here, we report that cesium cation (Cs(+)) directs the formation of solid electrolyte interphase on graphite anode in PC-rich electrolytes through its preferential solvation by ethylene carbonate (EC) and the subsequent higher reduction potential of the complex cation. Effective suppression of PC-decomposition and graphite-exfoliation is achieved by adjusting the EC/PC ratio in electrolytes to allow a reductive decomposition of Cs(+)-(EC)m (1 <= m <= 2) complex preceding that of Li(+)-(PC)n (3 <= n <= 5). Such Cs(+) directed interphase is stable, ultrathin, and compact, leading to significant improvement in battery performances. In a broader context, the accurate tailoring of interphasial chemistry by introducing a new solvation center represents a fundamental breakthrough in manipulating interfacial reactions that once were elusive to control. PMID- 26369298 TI - Structural Properties of Green Tea Catechins. AB - Green tea catechins are polyphenols which are believed to provide health benefits; they are marketed as health supplements and are studied for their potential effects on a variety of medical conditions. However, their mechanisms of action and interaction with the environment at the molecular level are still not well-understood. Here, by means of atomistic simulations, we explore the structural properties of four green tea catechins, in the gas phase and water solution: specifically, (-)-epigallocatechin-3-gallate, which is the most abundant, (-)-epicatechin-3-gallate, (-)-epigallocatechin-3-O-(3-O-methyl) gallate, and (-)-epigallocatechin. We characterize the free energy conformational landscapes of these catechins at ambient conditions, as a function of the torsional degrees of freedom of the pholyphenolic rings, determining the stable conformers and their connections. We show that these free energy landscapes are only subtly influenced by the interactions with the solvent and by the structural details of the polyphenolic rings. However, the number and position of the hydroxyl groups (or their sustituents) and the presence/absence of the galloyl moiety have significant impact on the selected catechin solvation shells and hydrogen bond capabilities, which are ultimately linked to their ability to interact with and affect the biological environment. PMID- 26369299 TI - The Curse of Expertise: When More Knowledge Leads to Miscalibrated Explanatory Insight. AB - Does expertise within a domain of knowledge predict accurate self-assessment of the ability to explain topics in that domain? We find that expertise increases confidence in the ability to explain a wide variety of phenomena. However, this confidence is unwarranted; after actually offering full explanations, people are surprised by the limitations in their understanding. For passive expertise (familiar topics), miscalibration is moderated by education; those with more education are accurate in their self-assessments (Experiment 1). But when those with more education consider topics related to their area of concentrated study (college major), they also display an illusion of understanding (Experiment 2). This "curse of expertise" is explained by a failure to recognize the amount of detailed information that had been forgotten (Experiment 3). While expertise can sometimes lead to accurate self-knowledge, it can also create illusions of competence. PMID- 26369300 TI - Nocardiopsis species: a potential source of bioactive compounds. AB - Members of the genus Nocardiopsis are an ecologically versatile and biotechnologically important group of Actinomycetes. Most of the isolates are halotolerant or halophilic and they prevail in soils, marine environments or hypersaline locations. To aid their survival under these conditions, they mainly produce extremozymes, compatible solutes, surfactants and bioactive compounds. The current review details the bioactive compounds obtained for this genus. Important antimicrobial agents obtained from this genus include polyketides, phenzines, quinoline alkaloids, terphenyls, proteins, thiopeptides and amines. Polyketides and peptides displaying potent anticancer activities are also significant. Tumour promoting agents, P-glycoprotein (P-gp) inhibitors, immunomodulators and protein kinase inhibitors are other relevant products obtained from Nocardiopsis species. Structurally, polyketides (synthesized by polyketide synthases) and peptides (made by nonribosomal peptide synthetases or cyclodipeptide synthases) are important compounds. Considered here are also toxins, anti photoaging and adipogenic agents produced by this genus. The gene clusters mediating the synthesis of bioactive compounds have been described. Commercially available products (Apoptolidins and K-252a) derived from this genus have also been described. This review highlights the significance of a single genus in producing an assortment of compounds with varied biological activities. On account of these features, the members of this genus have established a place for themselves and are of considerable value in producing compounds with profound bio-medical applications. PMID- 26369301 TI - Quasiracemate Crystal Structures of Magainin 2 Derivatives Support the Functional Significance of the Phenylalanine Zipper Motif. AB - Quasiracemic crystallography has been used to explore the significance of homochiral and heterochiral associations in a set of host-defense peptide derivatives. The previously reported racemic crystal structure of a magainin 2 derivative displayed a homochiral antiparallel dimer association featuring a "phenylalanine zipper" notable for the dual roles of phenylalanines in mediating dimerization and formation of an exposed hydrophobic swath. This motif is seen as well in two new quasiracemate crystals that contain the d form of the magainin 2 derivative along with an l-peptide in which one Ala has been replaced by a beta amino acid residue. This structural trend supports the hypothesis that the Phe zipper motif has functional significance. PMID- 26369302 TI - The unannounced patient in the corridor: trust, friction and person-centered care. AB - In this study, a Swedish cancer clinic was studied where three to four unscheduled patients sought support from the hospital on a daily basis for pain and nutrition problems. The clinic was neither staffed nor had a budget to handle such return visits. In order to offer the patients a better service and decrease the workload of the staff in addition to their everyday activities, a multidisciplinary team was established to address the unscheduled return visits. The team was supposed to involve the patient, build trust, decrease the friction, and contribute to a successful rehabilitation process. Data were collected from the patients and the staff. Patients who encountered the team (intervention) and patients who encountered the regular ad hoc type of organization (control) answered a questionnaire measuring trust and friction. Nurses in the control group spent 35% of their full-time employment, and the intervention group staffed with nurses spent 30% of their full-time employment in addressing the needs of these return patients. The patients perceived that trust between them and the staff was high. In summary, it was measured as being 4.48 [standard deviation (SD) = 0.82] in the intervention group and 4.41 (SD = 0.79) in the control group using the 5-point Likert scale. The data indicate that using a multidisciplinary team is a promising way to handle the problems of unannounced visits from patients. Having a team made it cost effective for the clinic and provided a better service than the traditional ad hoc organization. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26369305 TI - Surface Conditioning Protocol for the Adhesion of Resin-based Cements to Base and Noble Alloys: How to Condition and Why? PMID- 26369306 TI - [The Proceedings of the 140th Tokai-Hokuriku Regional Meeting of the Japanese Society of Neurology]. PMID- 26369307 TI - [The Proceedings of the 96th Hokkaido Regional Meeting of the Japanese Society of Neurology]. PMID- 26369310 TI - [Editor's Note]. PMID- 26369311 TI - Genotypic relatedness and antimicrobial resistance of Staphylococcus schleiferi in clinical samples from dogs in different geographic regions of the United States. AB - BACKGROUND: Staphylococcus schleiferi is a known pathogen that can cause canine skin and ear infections. The aim of this study was to determine the molecular epidemiology and antimicrobial susceptibility of clinical veterinary isolates from different geographic regions in the United States. HYPOTHESIS: It was hypothesized that S. schleiferi would maintain genotypic homogeneity across the different geographic regions and that meticillin-resistant (MR) isolates of S. schleiferi would predominate. METHODS: Isolates were identified as S. schleiferi by a commercial microbiology identification system and confirmed by nuc gene PCR. Antibiotic susceptibility data were collected and PBP2a latex agglutination testing was performed on MR isolates. Pulsed-field gel electrophoresis (PFGE) was performed and clonal clusters were identified with a Dice coefficient similarity of >80%. RESULTS: There were 116 isolates from the Mid-Atlantic region and 101 from across the United States. Of these 217 isolates, 209 (96%) were obtained from cutaneous sites. Of the Mid-Atlantic isolates, 62% (72 of 116) were MR and 16% (18 of 116) were multidrug-resistant (MDR). Of the isolates from the other geographic regions, 73% (74 of 101) were MR and 24% (24 of 101) were MDR. All MR isolates were positive by PBP2a latex agglutination. PFGE identified 155 individual pulsed-field profiles and three major pulsed-field types (PFT) that contained 61% (133 of 217) of the isolates. These pulsed-field types were geographically heterogeneous. CONCLUSIONS: This study demonstrates the dissemination of successful MR pulsed-field types of S. schleiferi across the United States. PMID- 26369312 TI - Helicobacter pylori: Helicobacter pylori gastritis--a novel distinct disease entity. AB - A global consensus report on Helicobacter pylori gastritis has been developed. Topics discussed include whether dyspepsia caused by H. pylori infection is separate from functional dyspepsia or not, the evaluation method for H. pylori induced gastritis, eradication therapy for H. pylori gastritis to prevent gastric carcinogenesis and management after H. pylori eradication. PMID- 26369313 TI - Diagnosis: A better FISH to detect pancreatobiliary cancer? PMID- 26369314 TI - HOMO-LUMO energy gap control in platinum(II) biphenyl complexes containing 2,2' bipyridine ligands. AB - A series of platinum(ii) biphenyl 2,2'-bipyridine complexes containing electron donating and electron-withdrawing moieties on the 4 and 4' positions of the bipyridine ligand exhibit emission from excited states in the 600 nm region of the spectrum upon excitation in the metal-to-ligand charge transfer transition located near 450 nm. These complexes are distorted from planarity based on both single crystal structure determinations and density functional theory (DFT) calculations of isolated molecules in acetonitrile. The DFT also reveals the geometry of the lowest-lying triplet state (LLTS) of each complex that is important for emission behavior. The LLTS are assigned based on the electron spin density distributions and correlated with the singlet excited states to understand the mechanism of electronic excitation and relaxation. Time-dependent DFT calculations are performed to compute the singlet excited state energies of these complexes so as to help interpret their UV-Vis absorption spectra. Computational and experimental results, including absorption and emission energy maxima, electrochemical reduction potentials, LLTS, singlet excited states, and LUMO and HOMO energies, exhibit linear correlations with the Hammett constants for para-substituents sigmap. These correlations are employed to screen complexes that have not yet been synthesized. The correlation analysis indicates that the electronic structure and the HOMO-LUMO energy gap in Pt(ii) complexes can be effectively controlled using electron-donating and electron-withdrawing moieties covalently bonded to the ligands. The information presented in this paper provides a better understanding of the fundamental electronic and thermodynamic behavior of these complexes and could be used to design systems with specific applications. PMID- 26369315 TI - Acid extraction of molybdenum, nickel and cobalt from mineral sludge generated by rainfall water at a metal recycling plant. AB - This study investigated the leaching yields of Mo, Ni and Co from a mineral sludge of a metal recycling plant generated by rainfalls. The investigated mineral sludge had a complex heterogeneous composition, consisting of particles of settled soil combined with metal-bearing particles (produced by catalysts, metallic oxides and battery recycling). The leaching potential of different leaching reagents (stand-alone strong acids (HNO3 (68%), H2SO4 (98%) and HCl (36%)) and acid mixtures (aqua regia (nitric + hydrochloric (1:3)), nitric + sulphuric (1:1) and nitric + sulphuric + hydrochloric (2:1:1)) was investigated at changing operational parameters (solid-liquid (S/L) ratio, leaching time and temperature), in order to select the leaching reagent which achieves the highest metal leaching yields. Sulphuric acid (98% H2SO4) was found to be the leachant with the highest metal leaching potential. The optimal leaching conditions were a three-stage successive leaching at 80 degrees C with a leaching time of 2 h and S/L ratio of 0.25 g L(-1). Under these conditions, the achieved mineral sludge sample leaching yields were 85.5%, 40.5% and 93.8% for Mo, Ni and Co, respectively. The higher metal leaching potential of H2SO4 in comparison with the other strong acids/acid mixtures is attributed to the fact that H2SO4 is a diacidic compound, thus it has more H(+) ions, resulting in its stronger oxidizing power and corrosiveness. PMID- 26369316 TI - Offline: Medicine's precarious place in the history of humanity. PMID- 26369317 TI - No faith in physic. PMID- 26369318 TI - Agnes Martin: the fragility of innocence. PMID- 26369319 TI - Bone mineral density of postmenopausal women with rheumatoid arthritis depends on disease duration regardless of treatment. AB - The aim of this study was to determine the associations of disease activity and disease duration with the bone mineral density (BMD) in rheumatoid arthritis (RA) patients. We also evaluated the associations of biological drugs with bone loss. A total of 138 postmenopausal RA patients were retrospectively assessed to identify the associations of disease activity, disease duration, and biological drug use with BMD. We assessed the associations of disease duration, a C-reactive protein based disease activity score in 28 joints (DAS28), simplified disease activity index, clinical disease activity index, health assessment questionnaire scores, and the use of biological drugs with the lumbar spine, total hip, and femoral neck BMDs using univariate and multivariate linear regression analyses in bisphosphonate treatment and non-bisphosphonate treatment groups at 1 year of follow-up. The multivariate linear regression analyses showed that disease duration was significantly related to the BMD of the femoral neck and total hip regardless of bisphosphonate treatment. The use of biological drugs was not significantly associated with BMD. Hip BMD in postmenopausal women with RA depends on the disease duration regardless of bisphosphonate use. Biological drugs for RA treatment were not negatively associated with general bone loss. PMID- 26369320 TI - Identification of a progenitor cell population destined to form fracture fibrocartilage callus in Dickkopf-related protein 3-green fluorescent protein reporter mice. AB - Fracture healing is a complex biological process involving the proliferation of mesenchymal progenitor cells, and chondrogenic, osteogenic, and angiogenic differentiation. The mechanisms underlying the proliferation and differentiation of mesenchymal progenitor cells remain unclear. Here, we demonstrate Dickkopf related protein 3 (Dkk3) expression in periosteal cells using Dkk3-green fluorescent protein reporter mice. We found that proliferation of mesenchymal progenitor cells began in the periosteum, involving Dkk3-positive cell proliferation near the fracture site. In addition, Dkk3 was expressed in fibrocartilage cells together with smooth muscle alpha-actin and Col3.6 in the early phase of fracture healing as a cell marker of fibrocartilage cells. Dkk3 was not expressed in mature chondrogenic cells or osteogenic cells. Transient expression of Dkk3 disappeared in the late phase of fracture healing, except in the superficial periosteal area of fracture callus. The Dkk3 expression pattern differed in newly formed type IV collagen positive blood vessels and the related avascular tissue. This is the first report that shows Dkk3 expression in the periosteum at a resting state and in fibrocartilage cells during the fracture healing process, which was associated with smooth muscle alpha-actin and Col3.6 expression in mesenchymal progenitor cells. These fluorescent mesenchymal lineage cells may be useful for future studies to better understand fracture healing. PMID- 26369321 TI - Oral health-related quality of life and related factors among residents in a disaster area of the Great East Japan Earthquake and giant tsunami. AB - BACKGROUND: Oral health is one of the most important issues for disaster survivors. The aim of this study was to determine post-disaster distribution of oral health-related quality of life (OHRQoL) and related factors in survivors of the Great East Japan Earthquake and Tsunami. METHODS: Questionnaires to assess OHRQoL, psychological distress, disaster-related experiences, and current systemic-health and economic conditions were sent to survivors over 18 years of age living in Otsuchi, one of the most severely damaged municipalities. OHRQoL and psychological distress were assessed using the General Oral Health Assessment Index (GOHAI) and the Kessler Psychological Distress Scale (K6), Japanese version, respectively. Among 11,411 residents, 1,987 returned the questionnaire (response rate, 17.4%) and received an oral examination to determine number of present teeth, dental caries status, and tooth-mobility grade, and to assess periodontal health using the Community Periodontal Index. Relationships between GOHAI and related factors were examined by nonparametric bivariate and multinomial logistic regression analyses using GOHAI cutoff points at the 25(th) and 50(th) national standard percentiles. RESULTS: GOHAI scores were significantly lower in the 50-69-age group compared with other age groups in this study and compared with the national standard score. In bivariate analyses, all factors assessed in this study (i.e., sex, age, evacuation from home, interruption of dental treatment, lost or fractured dentures, self-rated systemic health, serious psychological distress (SPD), economic status, number of teeth, having decayed teeth, CPI code, and tooth mobility) were significantly associated with OHRQoL. Subsequent multinomial logistic regression analyses revealed that participants of upper-middle age, who had received dental treatment before the disaster, who had lost or fractured dentures, and who had clinical oral health problems were likely to show low levels of OHRQoL. In addition, perceived systemic health and SPD were also related with OHRQoL. CONCLUSIONS: OHRQoL of disaster survivors was associated with oral problems stemming from the disaster in addition to factors related to OHRQoL in ordinary times such as clinical oral status and perceived systemic health. Furthermore, SPD was also associated with OHRQoL, which suggests the disaster's great negative impact on both oral and mental health conditions. PMID- 26369323 TI - Paraspinal extramedullary hematopoiesis in hereditary spherocytosis with a concurrent follicular lymphoma: case report and review of the literature. AB - We report an unusual case of a 70-year-old male with history of hereditary spherocytosis (HS) and secondary paraspinal extramedullary hematopoiesis with a concurrent follicular lymphoma. The lesion presented as a thoracic paraspinal mass of 9 cm, extending longitudinally between T6 and T9 vertebral bodies. Incisional biopsy revealed that this mass included mature hematopoietic tissue compatible with extramedullary hematopoiesis (EMH). The tissue also presented an extensive and diffuse infiltration by an atypical lymphoid population composed predominantly by small cells. The immunohistochemical study revealed that the atypical lymphoid population had a germinal center phenotype, consistent with the diffuse variant of follicular lymphoma (FL). The simultaneous presence of both EMH and FL in the same lesion made the interpretation and the final diagnosis of this case difficult. The presence of EMH in this clinical context may eclipse the diagnosis of the underlying lymphoproliferative neoplasm. The close association between the tumor cells and extramedullary hematopoietic tissue in the absence of lymphadenopathies or other tissue involvement suggests a relationship of this tumor with the recently described primary FL of the bone marrow. PMID- 26369324 TI - Converging or Crossing Curves: Untie the Gordian Knot or Cut it? Appropriate Statistics for Non-Proportional Hazards in Decitabine DACO-016 Study (AML). AB - INTRODUCTION: Among patients with acute myeloid leukemia (AML), the DACO-016 randomized study showed reduction in mortality for decitabine [Dacogen((r)) (DAC), Eisai Inc., Woodcliff Lake, NJ, USA] compared with treatment choice (TC): at primary analysis the hazard ratio (HR) was 0.85 (95% confidence interval 0.69 1.04; stratified log-rank P = 0.108). With two interim analyses, two-sided alpha was adjusted to 0.0462. With 1-year additional follow-up the HR reached 0.82 (nominal P = 0.0373). These data resulted in approval of DAC in the European Union, though not in the United States. Though pre-specified, the log-rank test could be considered not optimal to assess the observed survival difference because of the non-proportional hazard nature of the survival curves. METHODS: We applied the Wilcoxon test as a sensitivity analysis. Patients were randomized to DAC (N = 242) or TC (N = 243). One-hundred and eight (44.4%) patients in the TC arm and 91 (37.6%) patients in the DAC arm selectively crossed over to subsequent disease modifying therapies at progression, which might impact the survival beyond the median with resultant converging curves (and disproportional hazards). RESULTS: The stratified Wilcoxon test showed a significant improvement in median (CI 95%) overall survival with DAC [7.7 (6.2; 9.2) months] versus TC [5.0 (4.3; 6.3) months; P = 0.0458]. CONCLUSION: Wilcoxon test indicated significant increase in survival for DAC versus TC compared to log-rank test. FUNDING: Janssen-Cilag GmbH. PMID- 26369325 TI - Interprofessional collaboration milestones: advocating for common assessment criteria in graduate medical education. AB - BACKGROUND: Milestone-based assessments of resident physicians inform critical decisions regarding resident competence and advancement. Thus, it is essential that milestone evaluations are based upon strong validity evidence and that consistent evaluation criteria are used across residency programs. A common approach to assessment of interprofessional collaboration milestones is particularly important since standardized measures of individual resident competence in interprofessional collaboration have not been established. DISCUSSION: We propose that assessments of interprofessional collaboration in graduate medical education meet common criteria, namely, these assessments should: 1) measure competency of an individual resident, 2) occur in the context of an interprofessional team, 3) be ascertained via direct observation of the resident, 4) be performed in a real-world clinical practice setting (such as a hospital ward, outpatient clinic, or operating room). We present the evidence based rationale for these criteria and cite examples of published assessment instruments that fulfill one or more of the criteria, however further research is needed to ensure fidelity of assessments. The proposed criteria may assist residency educators as they endeavor to provide robust and consistent assessments of interprofessional collaboration milestones. PMID- 26369326 TI - Improving documentation and coding for acute organ dysfunction biases estimates of changing sepsis severity and burden: a retrospective study. AB - INTRODUCTION: Claims-based analyses report that the incidence of sepsis associated organ dysfunction is increasing. We examined whether coding practices for acute organ dysfunction are changing over time and if so, whether this is biasing estimates of rising severe sepsis incidence and severity. METHODS: We assessed trends from 2005 to 2013 in the annual sensitivity and incidence of discharge ICD-9-CM codes for organ dysfunction (shock, respiratory failure, acute kidney failure, acidosis, hepatitis, coagulopathy, and thrombocytopenia) relative to standardized clinical criteria (use of vasopressors/inotropes, mechanical ventilation for >= 2 consecutive days, rise in baseline creatinine, low pH, elevated transaminases or bilirubin, abnormal international normalized ratio or low fibrinogen, and decline in platelets). We studied all adult patients with suspected infection (defined by >= 1 blood culture order) at two US academic hospitals. RESULTS: Acute organ dysfunction codes were present in 57,273 of 191,695 (29.9%) hospitalizations with suspected infection, most commonly acute kidney failure (60.2% of cases) and respiratory failure (28.9%). The sensitivity of all organ dysfunction codes except thrombocytopenia increased significantly over time. This was most pronounced for acute kidney failure codes, which increased in sensitivity from 59.3% in 2005 to 87.5% in 2013 relative to a fixed definition for changes in creatinine (p = 0.019 for linear trend). Acute kidney failure codes were increasingly assigned to patients with smaller creatinine changes: the average peak creatinine change associated with a code was 1.99 mg/dL in 2005 versus 1.49 mg/dL in 2013 (p <0.001 for linear decline). The mean number of dysfunctional organs in patients with suspected infection increased from 0.32 to 0.59 using discharge codes versus 0.69 to 0.79 using clinical criteria (p < 0.001 for both trends and comparison of the two trends). The annual incidence of hospitalizations with suspected infection and any dysfunctional organ rose an average of 5.9% per year (95% CI 4.3, 7.4%) using discharge codes versus only 1.1% (95% CI 0.1, 2.0 %) using clinical criteria. CONCLUSIONS: Coding for acute organ dysfunction is becoming increasingly sensitive and the clinical threshold to code patients for certain kinds of organ dysfunction is decreasing. This accounts for much of the apparent rise in severe sepsis incidence and severity imputed from claims. PMID- 26369327 TI - Genome-wide association study for female fertility in Nordic Red cattle. AB - BACKGROUND: The Nordic Red Cattle (NRC) consists of animls belonging to the Danish Red, Finnish Ayrshire, and Swedish Red breeds. Compared to the Holstein breed, NRC animals are smaller, have a shorter calving interval, lower mastitis incidence and lower rates of stillborn calves, however they produce less milk, fat and protein. Female fertility is an important trait for the dairy cattle farmer. Selection decisions in female fertilty in NRC are based on the female fertility index (FTI). FTI is a composite index including a number of sub-indices describing aspects of female fertility in dairy cattle. The sub-traits of FTI are: number of inseminations per conception (AIS) in cows (C) and heifers (H), the length in days of the interval from calving to first insemination (ICF) in cows, days from first to last insemination (IFL) in cows and heifers, and 56-day non-return rate (NRR) in cows and heifers. The aim of this study was first to identify QTL for FTI by conducting a genome scan for variants associated with fertility index using imputed whole genome sequence data based on 4207 Nordic Red sires, and subsequently analyzing which of the sub-traits were affected by each FTI QTL by associating them with the sub-traits. RESULTS: A total 17,388 significant SNP markers (-log10(P) > 8.25) were detected for FTI distributed over 25 chromosomes. The chromosomes with the most significant markers were tested for associations with the underlying sub-traits: BTA1 (822 SNP), BTA2 (220 SNP), BTA3 (83 SNP), BTA5 (195 SNP), two regions on BTA6 (503 SNP), BTA13 (980 SNP), BTA15 (23 SNP), BTA20 (345 SNP), and BTA24 (104 SNP). The fertility traits underlying the FTI peak area were: BTA1 (IFLC, IFLH), BTA2 (AISH, IFLH, NRRH), BTA3 (AISH, NRRH), BTA5 (AISC, AISH, IFLH), BTA6 (region 1: AISH, NRRH; region 2: AISH, IFLH), BTA13 (IFLH, IFLC), BTA15 (IFLC, NRRH), and BTA24 (AISH, IFLH). For BTA20 all sub-traits had SNP markers with a -log10(P) > 10. Furthermore the genes assigned to the most significant SNP for FTI were located on BTA6 (GPR125), BTA13 (ANKRD60), BTA15 (GRAMD1B), and BTA24 (ZNF521). CONCLUSION: This study 1) shows that many markers within FTI QTL regions were significantly associated with both AISH and IFLH, and 2) identified candidate genes for FTI located on BTA6 (GPR125), BTA13 (ANKRD60), BTA15 (GRAMD1B), and BTA24 (ZNF521). It is not known how the genes/variants identified in this study regulate female fertility, however the majority of these genes were involved in protein binding, 3) a SNP in a QTL region for FTI on BTA20 was previously validated in three cattle breeds. PMID- 26369328 TI - Advances in Management of Pediatric Ependymomas. AB - Ependymomas are a heterogeneous group of neuroepithelial tumors of children and adults. In pediatric cases, the standard of care has long consisted of neurosurgical resection to the greatest extent acceptable followed by adjuvant involved field irradiation. Complete macroscopic surgical resection has remained the only consistent clinical variable known to improve survival. Adjuvant chemotherapy has yet to predictably affect outcome, possibly due to the molecular heterogeneity of histologically similar tumors. The administration of chemotherapy subsequently remains limited to clinical trials. However, recent comprehensive genomic, transcriptomic, and epigenetic interrogations of ependymomas have uncovered unique molecular characteristics and subtypes that correlated with clinical features such as age, neuroanatomical location, and prognosis. These findings represent a potential paradigm shift and provide a biologic rationale for targeted therapeutic strategies and risk-adapted administration of conventional treatment modalities. In this review, we focus on intracranial WHO grade II and III ependymoma of children and discuss conventional management strategies, followed by recent biologic findings and novel therapeutics currently under investigation. PMID- 26369329 TI - A versatile transgenic allele for mouse overexpression studies. AB - For the analysis of gene function in vivo, gene overexpression in the mouse provides an alternative to loss-of-function knock-out approaches and can help reveal phenotypes where compensatory mechanisms are at play. Furthermore, when multiple lines overexpressing a gene-of-interest at varying levels are studied, the consequences of differences in gene dosage can be explored. Despite these advantages, inherent shortcomings in the methodologies used for the generation of gain-of-function transgenic mouse models have limited their application to functional gene analysis, and the necessity for multiple lines comes at a significant animal and financial cost. The targeting of transgenic overexpression constructs at single copy into neutral genomic loci is the preferred method for the generation of such models, which avoids the unpredictable outcomes associated with conventional random integration. However, despite the increased reliability that targeted transgenic methodologies provide, only one expression level results, as defined by the promoter used. Here, we report a new versatile overexpression allele, the promoter-switch allele, which couples PhiC31 integrase targeted transgenesis with Flp recombinase promoter switching and Cre recombinase activation. These recombination switches allow the conversion of different overexpression alleles, combining the advantages of transgenic targeting with tunable transgene expression. With this approach, phenotype severity can be correlated with transgene expression in a single mouse model, providing a cost effective solution amenable to systematic gain-of-function studies. PMID- 26369330 TI - Non-invasive focus localization, right ventricular epicardial potential mapping in patients with an MRI-conditional pacemaker system - a pilot study. AB - BACKGROUND: With the advent of magnetic resonance imaging (MRI) conditional pacemaker systems, the possibility of performing MRI in pacemaker patients has been introduced. Besides for the detailed evaluation of atrial and ventricular volumes and function, MRI can be used in combination with body surface potential mapping (BSPM) in a non-invasive inverse potential mapping (IPM) strategy. In non invasive IPM, epicardial potentials are reconstructed from recorded body surface potentials (BSP). In order to investigate whether an IPM method with a limited number of electrodes could be used for the purpose of non-invasive focus localization, it was applied in patients with implanted pacing devices. Ventricular paced beats were used to simulate ventricular ectopic foci. METHODS: Ten patients with an MRI-conditional pacemaker system and a structurally normal heart were studied. Patient-specific 3D thorax volume models were reconstructed from the MRI images. BSP were recorded during ventricular pacing. Epicardial potentials were inversely calculated from the BSP. The site of epicardial breakthrough was compared to the position of the ventricular lead tip on MRI and the distance between these points was determined. RESULTS: For all patients, the site of earliest epicardial depolarization could be identified. When the tip of the pacing lead was implanted in vicinity to the epicardium, i.e. right ventricular (RV) apex or RV outflow tract, the distance between lead tip position and epicardial breakthrough was 6.0 +/- 1.9 mm. CONCLUSIONS: In conclusion, the combined MRI and IPM method is clinically applicable and can identify sites of earliest depolarization with a clinically useful accuracy. PMID- 26369331 TI - Intestinal Helminths of Wild Bonobos in Forest-Savanna Mosaic: Risk Assessment of Cross-Species Transmission with Local People in the Democratic Republic of the Congo. AB - Phylogenetic and geographic proximities between humans and apes pose a risk of zoonotic transmission of pathogens. Bonobos (Pan paniscus) of the Bolobo Territory, Democratic Republic of the Congo, live in a fragmented forest-savanna mosaic setting, a marginal habitat for this species used to living in dense forests. Human activities in the forest have increased the risk of contacts between humans and bonobos. Over 21 months (September 2010-October 2013), we monitored intestinal parasites in bonobo (n = 273) and in human (n = 79) fecal samples to acquire data on bonobo parasitology and to assess the risk of intestinal helminth transmission between these hosts. Coproscopy, DNA amplification, and sequencing of stored dried feces and larvae were performed to identify helminths. Little difference was observed in intestinal parasites of bonobos in this dryer habitat compared to those living in dense forests. Although Strongylids, Enterobius sp., and Capillaria sp. were found in both humans and bonobos, the species were different between the hosts according to egg size or molecular data. Thus, no evidence of helminth transmission between humans and bonobos was found. However, because humans and this threatened species share the same habitat, it is essential to continue to monitor this risk. PMID- 26369332 TI - Coloration of the Chilean Bellflower, Nolana paradoxa, interpreted with a scattering and absorbing layer stack model. AB - MAIN CONCLUSION: An absorbing-layer-stack model allows quantitative analysis of the light flux in flowers and the resulting reflectance spectra. It provides insight in how plants can optimize their flower coloration for attracting pollinators. The coloration of flowers is due to the combined effect of pigments and light-scattering structures. To interpret flower coloration, we applied an optical model that considers a flower as a stack of layers, where each layer can be treated with the Kubelka-Munk theory for diffusely scattering and absorbing media. We applied our model to the flowers of the Chilean Bellflower, Nolana paradoxa, which have distinctly different-colored adaxial and abaxial sides. We found that the flowers have a pigmented, strongly scattering upper layer, in combination with an unpigmented, moderately reflecting lower layer. The model allowed quantitative interpretation of the reflectance and transmittance spectra measured with an integrating sphere. The absorbance spectrum of the pigment measured with a microspectrophotometer confirmed the spectrum derived by modeling. We discuss how different pigment localizations yield different reflectance spectra. The absorbing layer stack model aids in understanding the various constraints and options for plants to tune their coloration. PMID- 26369333 TI - Effect of low-level laser therapy (904 nm) and static stretching in patients with knee osteoarthritis: a protocol of randomised controlled trial. AB - BACKGROUND: Osteoarthritis (OA) is a highly prevalent and disabling disease. It is estimated that by 2030 the prevalence of symptomatic OA could reach 30 % of the population above 60 years. This randomised controlled trial will investigate the effect of low-level laser therapy (LLLT) and static stretching exercises, as monotherapy and in combination, on pain, quality of life, function, mobility, knee range of motion (KROM) and hamstring shortening in participants with knee OA. METHODS: This study will involve 145 people aged 50-75 years with symptomatic radiographic knee OA. It will consist of two types of treatments: Low-level laser therapy (LLLT) and stretching exercises. The patients will be randomly allocated to five groups LLLTACTIVE+Stretch, LLLTPLACEBO+Stretch, Stretch, LLLT and Control (n = 29 each). Treatment frequency will be three sessions/week for all active groups. LLLT will involve the use of a Gallium-Arsenide laser (904 nm, 40 milliwatts, 3 J/point, 27 J/knee) over 24 sessions for the monotherapy group and 9 sessions for the LLLT+Stretch groups. Stretching will consist of seven exercises completed over 24 sessions. The control group will receive a booklet. Participants will be treated for 2 months (Stretch, LLLT and Control groups) or 3 months (LLLT + Stretch groups). Participants and the outcome assessor will be blind to treatment allocation throughout the study. The primary outcome is pain measured by Visual Analogue Scale. Secondary outcomes include quality of life assessed by Western Ontario and McMaster Universities Arthritis Index, function by Lequesne Algofunctional Index, mobility by Timed Up and Go Test, KROM by goniometry of knee flexion and hamstring shortening by popliteal angle. The statistical method will follow the principles of per-protocol analysis. DISCUSSION: Although exercise therapy is considered an effective treatment in patients with knee osteoarthritis, the knowledge of which exercise modalities would be the most appropriate for this population is lacking. LLLT has been used as resource to increase the effects of physical therapy. However, the specific dose and treatment frequency need to be better defined. The findings from this randomised controlled trial will provide evidence of the efficacy or otherwise, of LLLT and stretching exercises in the management of knee OA symptoms. TRIAL REGISTRATION: NCT01738737 at ClinicalTrials.gov. PMID- 26369334 TI - Purification and characterisation of the extracellular cholesterol oxidase enzyme from Enterococcus hirae. AB - BACKGROUND: Recently many efforts are being carried out to reduce cholesterol in foods. Out of the 50 selected isolates that were tested using the agar well diffusion method to assess their ability to decompose cholesterol, 24 bacterial isolates were screened based on their cholesterol-decomposition ability in liquid media. RESULTS: The bacterial isolate that displayed the highest cholesterol oxidase activity was identified as Enterococcus hirae. The maximal growth and cholesterol decomposition were achieved with a 1-day incubation under static conditions at 37 degrees C in cholesterol basal medium adjusted to pH 7 supplemented with 1 g/l cholesterol as the substrate, no additional carbon or nitrogen sources and 0.5 % CaSO4. The cholesterol oxidase enzyme (ChoX) produced by E. hirae was extracted at an (NH4)2SO4 saturation level of 80 % and purified with 79 % yield, resulting in 2.3-fold purification. The molecular weight of (ChoX) was 60 kDa. The optimal conditions required for the maximal activity of the purified COD enzyme produced by E. hirae were 30 min, 40 degrees C, pH 7.8, substrate concentration of 1 g/l and 200 ppm of MgCl2. The enzyme maintained approximately 36 % and 58.5 % of its activity after 18 days of storage at 4-8 degrees C. Also, the enzyme loss its activity by gradual thermal treatment, but it maintained 58.5 % of its activity at 95 degrees C for 2 hr. CONCLUSIONS: E. hirae Mil-31 isolated from milk had a great capacity to decompose cholesterol in basal medium supplemented with cholesterol under its optimal growth conditions. Decomposition process of cholesterol by this strain results from its production of cholesterol oxidase enzyme (ChoX). The highest specific enzyme activity and highest purification fold of purified enzyme were achieved after using Sephadex G 100. PMID- 26369335 TI - miR-506: a regulator of chemo-sensitivity through suppression of the RAD51 homologous recombination axis. AB - Ovarian carcinoma is the most lethal gynecologic malignancy. Resistance to platinum is considered the major problem affecting prognosis. Our recent study established that microRNA-506 (miR-506) expression was closely associated with progression-free survival and overall survival in two independent patient cohorts totaling 598 epithelial ovarian cancer cases. Further functional study demonstrated that miR-506 could augment the response to cisplatin and olaparib through targeting RAD51 and suppressing homologous recombination in a panel of ovarian cancer cell lines. Systemic delivery of miR-506 in an orthotopic ovarian cancer mouse model significantly augmented the cisplatin response, thus recapitulating the clinical observation. Therefore, miR-506 plays a functionally important role in homologous recombination and has important therapeutic value for sensitizing cancer cells to chemotherapy, especially in chemo-resistant patients with attenuated expression of miR-506. PMID- 26369336 TI - Chi8: a GPU program for detecting significant interacting SNPs with the Chi square 8-df test. AB - BACKGROUND: Determining interacting SNPs in genome-wide association studies is computationally expensive yet of considerable interest in genomics. FINDINGS: We present a program Chi8 that calculates the Chi-square 8 degree of freedom test between all pairs of SNPs in a brute force manner on a Graphics Processing Unit. We analyze each of the seven WTCCC genome-wide association studies that have about 5000 total case and controls and 400,000 SNPs in an average of 9.6 h on a single GPU. We also study the power, false positives, and area under curve of our program on simulated data and provide a comparison to the GBOOST program. Our program source code is freely available from http://www.cs.njit.edu/usman/Chi8. PMID- 26369338 TI - Spine maturation and pruning during development: Cadherin/Catenin complexes come to help. PMID- 26369337 TI - Sulforaphane improves the bronchoprotective response in asthmatics through Nrf2 mediated gene pathways. AB - BACKGROUND: It is widely recognized that deep inspiration (DI), either before methacholine (MCh) challenge (Bronchoprotection, BP) or after MCh challenge (Bronchodilation, BD) protects against this challenge in healthy individuals, but not in asthmatics. Sulforaphane, a dietary antioxidant and antiinflammatory phytochemical derived from broccoli, may affect the pulmonary bronchoconstrictor responses to MCh and the responses to DI in asthmatic patients. METHODS: Forty five moderate asthmatics were administered sulforaphane (100 MUmol daily for 14 days), BP, BD, lung volumes by body-plethsmography, and airway morphology by computed tomography (CT) were measured pre- and post sulforaphane consumption. RESULTS: Sulforaphane ameliorated the bronchoconstrictor effects of MCh on FEV1 significantly (on average by 21 %; p = 0.01) in 60 % of these asthmatics. Interestingly, in 20 % of the asthmatics, sulforaphane aggravated the bronchoconstrictor effects of MCh and in a similar number was without effect, documenting the great heterogeneity of the responsiveness of these individuals to sulforaphane. Moreover, in individuals in whom the FEV1 response to MCh challenge decreased after sulforaphane administration, i.e., sulforaphane was protective, the activities of Nrf2-regulated antioxidant and anti-inflammatory genes decreased. In contrast, individuals in whom sulforaphane treatment enhanced the FEV1 response to MCh, had increased expression of the activities of these genes. High resolution CT scans disclosed that in asthmatics sulforaphane treatment resulted in a significant reduction in specific airway resistance and also increased small airway luminal area and airway trapping modestly but significantly. CONCLUSION: These findings suggest the potential value of blocking the bronchoconstrictor hyperresponsiveness in some types of asthmatics by phytochemicals such as sulforaphane. PMID- 26369339 TI - Towards health equity: a framework for the application of proportionate universalism. AB - INTRODUCTION: The finding that there is a social gradient in health has prompted considerable interest in public health circles. Recent influential works describing health inequities and their causes do not always argue cogently for a policy framework that would drive the most appropriate solutions differentially across the social gradient This paper aims to develop a practice heuristic for proportionate universalism. METHODS: Through a review the proposed heuristic integrates evidence from welfare state and policy research, the literature on universal and targeted policy frameworks, and a multi-level governance approach that adopts the principle of subsidiarity. RESULTS: The proposed heuristic provides a more-grained analysis of different policy approaches, integral for operationalizing the concept of proportionate universalism. CONCLUSION: The proposed framework would allow governments at all levels, social policy developers and bureaucrats, public health professionals and activists to consider the appropriateness of distinctive policy objectives across distinctive population needs within universal welfare state principles. PMID- 26369340 TI - Edoxaban: a review in nonvalvular atrial fibrillation. AB - The factor Xa inhibitor edoxaban (Lixiana((r))) is a new direct oral anticoagulant recently approved in the EU for the prevention of stroke and systemic embolic events (SEE) in patients with nonvalvular atrial fibrillation and one or more risk factors. In the large, randomized, double-blind, double dummy, ENGAGE AF-TIMI 48 trial, oral edoxaban dosages of 30 and 60 mg once daily for a median treatment duration of 907 days in patients with moderate-to-high risk nonvalvular atrial fibrillation were noninferior to warfarin for the incidence of first stroke or SEE. Both high-dose and low-dose edoxaban were associated with significantly lower rates than warfarin of major bleeding, including intracranial haemorrhage, and death from cardiovascular causes. Edoxaban has a rapid onset of action, a short half-life, few drug interactions and offers the convenience of oral, once-daily, fixed-dose administration, without the need for coagulation monitoring and without regard to food. Therefore, edoxaban is an effective and well tolerated therapeutic option in patients with nonvalvular atrial fibrillation. PMID- 26369341 TI - Predictors of No-Reflow Phenomenon in Young Patients With Acute ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention. AB - No-reflow is of prognostic value in ST-segment elevation myocardial infarction (STEMI) but has not been extensively investigated in young patients. Young patients with STEMI admitted within 12 hours from symptom onset and treated by primary percutaneous coronary intervention (pPCI) were recruited. Patients were classified into 2 groups based on postintervention thrombolysis in myocardial infarction (TIMI) flow grade; no-reflow: TIMI flow grade 0, 1 or 2 (group 1; n = 27; 21 men, mean age: 42 +/- 4 years); and angiographic success: TIMI flow grade 3 (group 2; n = 118; 110 men, mean age: 43 +/- 4 years). Adjusted odds ratios were 13.79 for female gender (P < .001; confidence interval [CI] = 1.88-101.26), 2.09 for pain to balloon time (P < .017; CI = 1.14-3.812), 12.29 for high TIMI thrombus grade (P = .012; CI = 1.74-86.94), 0.04 for tirofiban use (P < .001; CI = 0.01-0.22), 5.19 for mean platelet volume (MPV; P < .001; CI = 2.44-11.01), and 1.008 for platelet-lymphocyte ratio (PLR; P = .034; CI = 1.001-1.016). In conclusion, female gender, pain to balloon time, high TIMI thrombus grade, tirofiban, MPV, and PLR were independent predictors of no-reflow in young patients with STEMI after pPCI. PMID- 26369342 TI - Modular Patterns of Phase Desynchronization Networks During a Simple Visuomotor Task. AB - By performing sensor-level analysis on magnetoencephalography (MEG) data we identified the dynamic evolution of the functional connectivity networks during a simple visuomotor task. The functional connectivity networks were constructed using the concept of phase-locking value (PLV). We illustrate that the task related activity is mediated by distinct complex networks related to the PLV desynchronization that configure their architecture dynamically during the task. These networks are prominent at beta and alpha band, and are characterized by coherent modular organization. Moreover the time for the development of the desynchronization networks at alpha band predicts the intra-subject variability of reaction time. Thus, the spatio-temporal dynamics and the structural properties of the emerged functional networks share common characteristics with the mechanism of coactivation and resting state networks. PMID- 26369343 TI - New Solutions to Reduce Discard of Kidneys Donated for Transplantation. AB - Kidney transplantation is a cost-saving treatment that extends the lives of patients with ESRD. Unfortunately, the kidney transplant waiting list has ballooned to over 100,000 Americans. Across large areas of the United States, many kidney transplant candidates spend over 5 years waiting and often die before undergoing transplantation. However, more than 2500 kidneys (>17% of the total recovered from deceased donors) were discarded in 2013, despite evidence that many of these kidneys would provide a survival benefit to wait-listed patients. Transplant leaders have focused attention on transplant center report cards as a likely cause for this discard problem, although that focus is too narrow. In this review, we examine the risks associated with accepting various categories of donated kidneys, including discarded kidneys, compared with the risk of remaining on dialysis. With the goal of improving access to kidney transplant, we describe feasible proposals to increase acceptance of currently discarded organs. PMID- 26369344 TI - Off-pump minimally invasive coronary artery bypass grafting using the bilateral internal thoracic arteries and the right gastroepiproic artery. AB - We report our initial experience of an off-pump total arterial minimally invasive coronary arterial bypass grafting (MICS CABG) with the use of bilateral internal thoracic arteries (BITA) and the right gastroepiproic artery. A 47-year old male with renal dysfunction secondary to diabetes mellitus was admitted for heart failure due to severe triple-vessel disease. Off-pump MICS CABG with total arterial grafts was elected because the patient refused to undergo median sternotomy due to the strong desire to regain the baseline function promptly. Total arterial grafts were selected to maximize the potential long-term outcome. There were no postoperative complications except temporary dialysis. Postoperative coronary computed tomography revealed the patency of all grafts. Our experience suggests that BITA can be safely harvested under direct vision in MICS CABG. Total arterial graft revascularization with BITA via minimally invasive approach may offer the benefits of MICS CABG while providing the undetermined but potentially superior conduit longevity of arterial grafts. PMID- 26369345 TI - Judge condemns "widespread incompetence" in IVF sector. PMID- 26369346 TI - A Framework to Assist Health Professionals in Recommending High-Quality Apps for Supporting Chronic Disease Self-Management: Illustrative Assessment of Type 2 Diabetes Apps. AB - BACKGROUND: This paper presents an approach to assist health professionals in recommending high quality apps for supporting chronic disease self-management. Most app reviews focus on popularity, aesthetics, functionality, usability, and information quality. There is no doubt these factors are important in selecting trustworthy apps which are appealing to users, but behavioral theory may be also be useful in matching the apps to user needs. OBJECTIVE: The framework developed aims to be methodologically sound, capable of selecting popular apps which include content covered by evidence-based programs, consistent with behavioral theory, as well as a patient-centered approach for matching apps to patients' individual needs. METHODS: A single disease-type 2 diabetes-was selected to illustrate how the framework can be applied as this was deemed to represent the types of strategies used in many chronic diseases. A systematic approach based on behavioral theory and recommendations from best practice guidelines was developed for matching apps to patients' needs. In March 2014, a series of search strategies was used to identify top-rated iPhone and Android health apps, representing 29 topics from five categories of type 2 diabetes self-management strategies. The topics were chosen from published international guidelines for the management of diabetes. The senior author (KH) assessed the most popular apps found that addressed these topics using the Behavioral Theory Content Survey (BTS), which is based on traditional behavioral theory. A tool to assist decision making when using apps was developed and trialed with health professionals for ease of use and understanding. RESULTS: A total of 14 apps were assessed representing all five topic categories of self-management. Total theoretical scores (BTS scores) were less than 50 on a 100-point scale for all apps. Each app scored less than 50% of the total possible BTS score for all four behavioral theories and for most of the 20 behavioral strategies; however, apps scored higher than 50% of the total possible BTS score for specific strategies related to their primary focus. Our findings suggest that the apps studied would be more effective when used in conjunction with therapy than as stand-alone apps. Apps were categorized according to topic and core intervention strategies. A framework for matching apps to identified patient needs was developed based on app categorization and principles of patient-centered care. The approach was well accepted and understood by a convenience sample of health practitioners. CONCLUSIONS: The framework presented can be used by health practitioners to better match apps with client needs. Some apps incorporate highly interactive strategies of behavioral theory, and when used as an adjunct may increase patient participation and the effectiveness of therapy. PMID- 26369347 TI - HIV Treatment and Prevention: A Simple Model to Determine Optimal Investment. AB - OBJECTIVE: To create a simple model to help public health decision makers determine how to best invest limited resources in HIV treatment scale-up and prevention. METHOD: A linear model was developed for determining the optimal mix of investment in HIV treatment and prevention, given a fixed budget. The model incorporates estimates of secondary health benefits accruing from HIV treatment and prevention and allows for diseconomies of scale in program costs and subadditive benefits from concurrent program implementation. Data sources were published literature. The target population was individuals infected with HIV or at risk of acquiring it. Illustrative examples of interventions include preexposure prophylaxis (PrEP), community-based education (CBE), and antiretroviral therapy (ART) for men who have sex with men (MSM) in the US. Outcome measures were incremental cost, quality-adjusted life-years gained, and HIV infections averted. RESULTS: Base case analysis indicated that it is optimal to invest in ART before PrEP and to invest in CBE before scaling up ART. Diseconomies of scale reduced the optimal investment level. Subadditivity of benefits did not affect the optimal allocation for relatively low implementation levels. The sensitivity analysis indicated that investment in ART before PrEP was optimal in all scenarios tested. Investment in ART before CBE became optimal when CBE reduced risky behavior by 4% or less. Limitations of the study are that dynamic effects are approximated with a static model. CONCLUSIONS: Our model provides a simple yet accurate means of determining optimal investment in HIV prevention and treatment. For MSM in the US, HIV control funds should be prioritized on inexpensive, effective programs like CBE, then on ART scale-up, with only minimal investment in PrEP. PMID- 26369348 TI - The Influence of Conduct Problems and Callous-Unemotional Traits on Academic Development Among Youth. AB - The present study attempted to address developmental differences within the large group of youth with conduct problems through an examination of the relationship between callous-unemotional traits and academic outcomes in an effort to expand the field's understanding of heterogeneity in outcomes associated with behavior problems. Data were collected from a cohort of 3rd grade students (N = 942; 51 % female; 45.6 % Hispanic/Latino, 41.1 % Black/African American, 4.7 % Non-Hispanic White; mean age = 8.07 years) in eighteen public elementary schools, as well as their parents and teachers. Hierarchical linear modeling revealed that callous unemotional traits were associated with lower quality student-teacher relationships and worse performance on standardized math and reading exams over and above the effects of conduct problems. These findings suggest that school based interventions may be particularly effective in ameliorating some of the deficits noted within this subset of youth exhibiting conduct problems. This finding has important policy implications as the field of developmental science attempts to design and enrich programs that focus on improving social-emotional learning. PMID- 26369349 TI - Racial Socialization, Racial Identity, and Academic Attitudes Among African American Adolescents: Examining the Moderating Influence of Parent-Adolescent Communication. AB - A significant gap remains in our understanding of the conditions under which parents' racial socialization has consequences for adolescents' functioning. The present study used longitudinal data to examine whether the frequency of communication between African American parents and adolescents (N = 504; 49 % female) moderates the association between parent reports of racial socialization (i.e., cultural socialization and preparation for bias) at 8th grade and adolescent reports of racial identity (perceived structural discrimination, negative public regard, success-oriented centrality) at 11th grade, and in turn, academic attitudes and perceptions. Parents' racial socialization practices were significant predictors of multiple aspects of adolescents' racial identity in families with high levels of communication, but they did not predict any aspects of adolescents' racial identity in families with low levels of communication. Results highlight the importance of including family processes when examining the relations between parents' racial socialization and adolescents' racial identity and academic attitudes and perceptions. PMID- 26369351 TI - Erratum To: Prevalence of cardiovascular disease risk factors among a Nigerian adult population: relationship with income level and accessibility to CVD risks screening. PMID- 26369350 TI - Loneliness and Attitudes Toward Aloneness in Adolescence: A Person-Centered Approach. AB - In adolescence, feeling lonely and dealing with time spent alone become particularly salient. The present study examined the co-occurrence of parent- and peer-related loneliness, and positive and negative attitudes toward aloneness, using cluster analysis. In three independent samples, covering about 1800 adolescents (61 % female), six meaningful groups were identified. These groups showed different associations with adolescents' self-esteem and personality, parental responsiveness and psychological control, and peer group functioning and friendships. An adaptive pattern of correlates was found for adolescents in three of the six groups, that is, the Indifference group (with rather low scores on the four constructs), the Moderate group (with moderate scores on the four constructs), and the Negative Attitude Toward Aloneness group. A rather maladaptive pattern of correlates was found for adolescents in the three other groups, that is, the Peer-Related Loneliness group, the Positive Attitude Toward Aloneness group, and the Parent-Related Loneliness group. More specifically, adolescents in the Peer-Related Loneliness and Positive Attitude Toward Aloneness groups may need assistance regarding their relations with their peers, whereas adolescents in the Parent-Related Loneliness group may need assistance regarding their relations with their parents. Implications of these findings for current understanding and optimal measurement of adolescents' loneliness and aloneness are discussed. PMID- 26369352 TI - The complete mitochondrial genome organization of Schizothorax Plagiostomus (Teleostei: Cyprinidae) from Northern Pakistan. AB - Schizothorax plagiostomus, a fresh water fish, is an economically important fish of Pakistan. In this study, the complete mitochondrial DNA (mtDNA) sequence of S. plagiostomus was explored. The mitogenome length was found to be 16 563bp with 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes and 2 non-coding regions: origin of light-strand replication (OL) and control region (D-loop). All genes were encoded on the heavy strand except ND6 and few tRNA genes. The overall base composition of S. plagiostomus of the heavy strand was T 25.5%, C 27.0%, A 29.8% and G 17.8%, A + T content 55.3% and G + C content 44.7%. The phylogenetic tree suggests that S. esocinus, S. progastus, S. richardsonii and S. plagiostomus may have closer affinities than other fish of the genus Schizothorax. This mitogenome sequence would be useful for phylogenetic analysis and conservation of this species in Pakistan. PMID- 26369353 TI - Survival Prospects and Circumstances of Death in Contemporary Adult Congenital Heart Disease Patients Under Follow-Up at a Large Tertiary Centre. AB - BACKGROUND: Adult congenital heart disease (ACHD) patients have ongoing morbidity and reduced long-term survival. Recently, the importance of specialized follow-up at tertiary ACHD centers has been highlighted. We aimed to assess survival prospects and clarify causes of death in a large cohort of patients at a single, tertiary center. METHODS AND RESULTS: We included 6969 adult patients (age 29.9 +/- 15.4 years) under follow-up at our institution between 1991 and 2013. Causes of death were ascertained from official death certificates. Survival was compared with the expected survival in the general age- and sex-matched population, and standardized mortality rates were calculated. Over a median follow-up time of 9.1 years (interquartile range, 5.2-14.5), 524 patients died. Leading causes of death were chronic heart failure (42%), pneumonia (10%), sudden-cardiac death (7%), cancer (6%), and hemorrhage (5%), whereas perioperative mortality was comparatively low. Isolated simple defects exhibited mortality rates similar to those in the general population, whereas patients with Eisenmenger syndrome, complex congenital heart disease, and Fontan physiology had much poorer long-term survival (P<0.0001 for all). The probability of cardiac death decreased with increasing patient's age, whereas the proportion of patients dying from noncardiac causes, such as cancer, increased. CONCLUSIONS: ACHD patients continue to be afflicted by increased mortality in comparison with the general population as they grow older. Highest mortality rates were observed among patients with complex ACHD, Fontan physiology, and Eisenmenger syndrome. Our data provide an overview over causes of mortality and especially the spectrum of noncardiac causes of death in contemporary ACHD patients. PMID- 26369355 TI - Acquired macrolide resistance genes in Haemophilus influenzae?-authors' response. PMID- 26369354 TI - Race, Socioeconomic Status, and Life Expectancy After Acute Myocardial Infarction. AB - BACKGROUND: Previous studies have been unable to disentangle the negative associations of black race and low socioeconomic status (SES) with long-term outcomes of patients after acute myocardial infarction (AMI). Such information could assist in efforts to address both racial and socioeconomic disparities. METHODS AND RESULTS: We used data from the Cooperative Cardiovascular Project, a prospective cohort study of Medicare beneficiaries hospitalized with AMI with 17 years of follow-up, to evaluate the relationship between race, area-level SES (measured by zip code-level median household income), and life expectancy after AMI. Life expectancy was estimated by using Cox proportional hazards regression with extrapolation using exponential models. Of the 141 095 patients with AMI, 6.3% were black and 6.8% resided in low-SES areas; 26% of black patients lived in low-SES areas in comparison with 5.7% of white patients. Post-myocardial infarction life expectancy estimates were shorter for black patients than for white patients across all socioeconomic levels in patients <= 75 years of age. After adjustment for patient and treatment characteristics, the association between race and life expectancy persisted but was attenuated. Younger black patients (<68 years) had shorter life expectancies than white patients, whereas older black patients had longer life expectancies. The largest white-black gap in life expectancy occurred in patients residing in high- and medium-SES areas (P=0.02 interaction). CONCLUSIONS: Black and white patients residing in low-SES areas have similar life expectancies after AMI, which are lower than those living in higher-SES areas. Racial disparities were most prominent among patients living in high-SES areas. PMID- 26369356 TI - mecC-positive MRSA in horses. PMID- 26369357 TI - Exercise training for managing behavioral and psychological symptoms in people with dementia: A systematic review and meta-analysis. AB - This systematic review and meta-analysis of randomized controlled trials assessed the effects of exercise on behavioral and psychological symptoms of dementia (BPSD, including depression) in people with dementia (PWD). Secondary outcomes for the effects of exercise were mortality and antipsychotic use. Twenty studies were included in this review (n=18 in the meta-analysis). Most studies used a multicomponent exercise training (n=13) as intervention; the control group was often a usual care (n=10) or a socially-active (n=8) group. Exercise did not reduce global levels of BPSD (n=4. Weighted mean difference -3.884; 95% CI -8.969 1.201; I(2)=69.4%). Exercise significantly reduced depression levels in PWD (n=7). Standardized mean difference -0.306; 95% CI -0.571 to -0.041; I(2)=46.8%); similar patterns were obtained in sensitivity analysis performed among studies with: institutionalized people (p=0.038), multicomponent training (p=0.056), social control group (p=0.08), and low risk of attrition bias (p=0.11). Exploratory analysis showed that the principal BPSD (other than depression) positively affected by exercise was aberrant motor behavior. Exercise had no effect on mortality. Data on antipsychotics were scarce. In conclusion, exercise reduces depression levels in PWD. Future studies should examine whether exercise reduces the use (and doses) of antipsychotics and other drugs often used to manage BPSD. PMID- 26369360 TI - Magnetic properties of ball-milled SrFe12O19 particles consolidated by Spark Plasma Sintering. AB - The room-temperature magnetic properties of ball-milled strontium hexaferrite particles consolidated by spark-plasma sintering are strongly influenced by the milling time. Scanning electron microscopy revealed the ball-milled SrFe12O19 particles to have sizes varying over several hundred nanometers. X-Ray powder diffraction studies performed on the ball-milled particles before sintering clearly demonstrate the occurrence of a pronounced amorphization process. During sintering at 950 degrees C, re-crystallization takes place, even for short sintering times of only 2 minutes and transformation of the amorphous phase into a secondary phase is unavoidable. The concentration of this secondary phase increases with increasing ball-milling time. The remanence and maximum magnetization values at 1T are weakly influenced, while the coercivity drops dramatically from 2340 Oe to 1100 Oe for the consolidated sample containing the largest amount of secondary phase. PMID- 26369359 TI - Is it time to think about the sodium glucose co-transporter 2 sympathetically? AB - Disturbances in glucose homeostasis are a key feature of the metabolic syndrome and type 2 diabetes. Renal glucose reabsorption is an important factor in glycaemic control. Glucose reabsorption in the proximal tubules is mediated by the sodium glucose co-transporter 2. The capacity for glucose reabsorption is increased in type 2 diabetes and contributes significantly to hyperglycaemia and impaired glucose control. Understanding the mechanisms underpinning the regulation of the sodium glucose co-transporter 2 is therefore of high clinical relevance. However, despite recent advances in the field and the availability of pharmacological inhibitors of this glucose transporter for the treatment of type 2 diabetes, the mechanisms that regulate sodium glucose co-transporter 2 expression are not fully understood. The sympathetic nervous system is an important modulator of glucose homeostasis, and sympathetic hyperactivity is a characteristic feature of obesity, the metabolic syndrome and type 2 diabetes. Sympathetic inhibition either achieved pharmacologically or by renal sympathetic denervation has been associated with improved glucose control. Importantly, sympathetic nerves innervate the proximal tubules of the kidney where they have been shown to regulate the expression of other transporters such as the sodium hydrogen exchanger 3. This review aims to explore the evidence for the regulation of sodium glucose co-transporter 2-mediated glucose reabsorption by the sympathetic nervous system. PMID- 26369362 TI - Kinetic and economic analysis of reactive capture of dilute carbon dioxide with Grignard reagents. AB - Carbon Dioxide Utilisation (CDU) processes face significant challenges, especially in the energetic cost of carbon capture from flue gas and the uphill energy gradient for CO2 reduction. Both of these stumbling blocks can be addressed by using alkaline earth metal compounds, such as Grignard reagents, as sacrificial capture agents. We have investigated the performance of these reagents in their ability to both capture and activate CO2 directly from dried flue gas (essentially avoiding the costly capture process entirely) at room temperature and ambient pressures with high yield and selectivity. Naturally, to make the process sustainable, these reagents must then be recycled and regenerated. This would potentially be carried out using existing industrial processes and renewable electricity. This offers the possibility of creating a closed loop system whereby alcohols and certain hydrocarbons may be carboxylated with CO2 and renewable electricity to create higher-value products containing captured carbon. A preliminary Techno-Economic Analysis (TEA) of an example looped process has been carried out to identify the electrical and raw material supply demands and hence determine production costs. These have compared broadly favourably with existing market values. PMID- 26369358 TI - RPE necroptosis in response to oxidative stress and in AMD. AB - Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in the elderly. The underlying mechanism of non-neovascular AMD (dry AMD), also named geographic atrophy (GA) remains unclear and the mechanism of retinal pigment epithelial (RPE) cell death in AMD is controversial. We review the history and recent progress in understanding the mechanism of RPE cell death induced by oxidative stress, in AMD mouse models, and in AMD patients. Due to the limitation of toolsets to distinguish between apoptosis and necroptosis (or necrosis), most previous research concludes that apoptosis is a major mechanism for RPE cell death in response to oxidative stress and in AMD. Recent studies suggest necroptosis as a major mechanism of RPE cell death in response to oxidative stress. Moreover, ultrastructural and histopathological studies support necrosis as major mechanism of RPE cells death in AMD. In this review, we discuss the mechanism of RPE cell death in response to oxidative stress, in AMD mouse models, and in human AMD patients. Based on the literature, we hypothesize that necroptosis is a major mechanism for RPE cell death in response to oxidative stress and in AMD. PMID- 26369361 TI - Single versus multiple session stereotactic body radiotherapy for spinal metastasis: the risk-benefit ratio. AB - Spine stereotactic body radiation therapy represents an important advancement in the management of spinal metastases that allows precise delivery of ablative doses of radiation therapy with excellent local control. Although the technique is being increasingly used in clinical practice, the optimal fractionation schedule remains uncertain. In this perspective paper, we review radiobiologic principles that support the use of multiple- versus single-fraction spine stereotactic body radiation therapy schedules and clinical data supporting the multiple-fraction approach. Specifically, we suggest that there may be a local control benefit of fractionation, while helping to limit the risk of toxicities such as vertebral body fracture, pain flare and radiation myelopathy. We conclude with future directions and the need for future study on this important topic. PMID- 26369363 TI - Epidemiology of Suicide and Associated Socio-Demographic Factors in Emergency Department Patients in 7 General Hospitals in Northwestern China. AB - BACKGROUND: This study aimed to illustrate the characteristics of suicide attempters treated in the Emergency Departments of 7 general hospitals in Xi'an and to provide relevant data for early psychological treatment. MATERIAL AND METHODS: Between October 2010 and September 2014, 155 suicide attempters were treated in the Emergency Departments. Data were collected using a semi-structured questionnaire. Descriptive statistics, chi-square tests, and multivariate analyses were used to identify the factors associated with suicidal behaviors. RESULTS: Females outnumbered males at a ratio of 3.7 to 1. The greatest proportion of cases was in the age group of 21 to 30 years (52.9%). Patients who finished middle school or high school accounted for most of the suicide attempters (50.3%). The most common method used for attempted suicide was drug ingestion (86.5%). The majority of cases attempted suicide at home (74.8%) during the night. Marriage frustration, work and study problems, family fanaticism and conflict, somatic disease, and history of mental disorders were all significantly associated with suicide attempts. The ratio of patients to be discharged or to die were similar in occupation, marital status, and the place of suicide attempt; however, the results were different in gender, age, educational level, methods used for suicide, time of day, and reason. CONCLUSIONS: Suicide is an important public health problem and is multidimensional in nature. Future studies with larger samples are expected to provide more specific knowledge of the effect of each social factor on the suicide risk in Chinese in order to improve the prevention of suicides. PMID- 26369364 TI - Mutation of histone H3 serine 86 disrupts GATA factor Ams2 expression and precise chromosome segregation in fission yeast. AB - Eukaryotic genomes are packed into discrete units, referred to as nucleosomes, by organizing around scaffolding histone proteins. The interplay between these histones and the DNA can dynamically regulate the function of the chromosomal domain. Here, we interrogated the function of a pair of juxtaposing serine residues (S86 and S87) that reside within the histone fold of histone H3. We show that fission yeast cells expressing a mutant histone H3 disrupted at S86 and S87 (hht2-S86AS87A) exhibited unequal chromosome segregation, disrupted transcriptional silencing of centromeric chromatin, and reduced expression of Ams2, a GATA-factor that regulates localization of the centromere-specific histone H3 variant CENP-A. We found that overexpression of ams2(+) could suppress the chromosome missegregation phenotype that arose in the hht2-S86AS87A mutant. We further demonstrate that centromeric localization of SpCENP-A(cnp1-1) was significantly compromised in hht2-S86AS87A, suggesting synergism between histone H3 and the centromere-targeting domain of SpCENP-A. Taken together, our work presents evidence for an uncharacterized serine residue in fission yeast histone H3 that affects centromeric integrity via regulating the expression of the SpCENP A-localizing Ams2 protein. [173/200 words]. PMID- 26369366 TI - Geriatric Disaster Preparedness. AB - INTRODUCTION: The elderly population has proven to be vulnerable in times of a disaster. Many have chronic medical problems for which they depend on medications or medical equipment. Some older adults are dependent on caregivers for managing their activities of daily living (ADLs), such as dressing, and their instrumental activities of daily living (IADLs), such as transportation. Problem A coordinated effort for disaster preparation in the elderly population is paramount. This study assessed the potential needs and plans of older adults in the face of a local disaster. METHODS: The setting was a community-based, university affiliated, urban emergency department (ED) that sees more than 77,000 adult patients per year. A survey on disaster plans and resources needed if evacuated was distributed to 100 community-residing ED patients and visitors aged 65 years and older from January through July 2013. Means and proportions are reported with 95% confidence intervals (CIs). RESULTS: Data were collected from 13 visitors and 87 patients. The mean age was 76 years, and 54% were female. Thirty-one responded that they had a disaster plan in place (31/100; CI, 22.4-41.4%). Of those 31, 94% (29/31; CI, 78.6-99.2%) had food and water as part of their plan, 62% (19/29; CI, 42.2-78.2%) had a supply of medication, and 35% (12/31; CI, 21.8-57.8%) had an evacuation plan. When asked what supplies the 100 subjects might need if evacuated, 33% (CI, 23.9-43.1%) needed a walker, 15% (CI, 8.6-23.5%) needed a wheelchair, 78% (CI, 68.6-85.7%) needed glasses, 17% (CI, 10.2-25.8%) needed a hearing aid, 16% (CI, 9.4-24.7%) needed a glucometer, 93% (CI, 86.1-97.1%) needed medication, 14% (CI, 7.8-22.4%) needed oxygen, 23% (CI, 15.2-32.5%) needed adult diapers, and 21% (CI, 13.2-30.3%) had medical equipment that required electricity. Many of the subjects also required help with one or more of their ADLS, the most common being dressing (17%; CI, 10.3-26.1%), or their IADLS, the most common being transportation (39%; CI, 29.7-49.7%). Only 42% (CI, 32.3-52.7%) were interested in learning more about disaster preparation. CONCLUSION: Only a minority of the older adults in the study population had a disaster plan in place. Most of the respondents would require medications, and many would require medical supplies if evacuated. PMID- 26369365 TI - Effect of methotrexate exposure at late gestation on development of telencephalon in rat fetal brain. AB - Pregnant rats were treated with 30 mg/kg of methotrexate (MTX) on gestation day (GD) 16, and fetal brains were examined time-dependently. On GD 20, the appearance of the telencephalon in the MTX group was different from that in the control group, and the major axis of the telencephalon of the MTX group was shortened, compared to that of the control group. In the sagittal section of the telencephalon in the MTX group on GD 20, histopathological findings of deformation and narrowing of the cerebral ventricle, the disturbance of the arrangement of the marginal cell layer of subventricular zone (SVZ) and thickening of telencephalic wall, cortical plate and ventricular zone (VZ)/SVZ were possibly attributable to neuronal migration disorders by MTX. Through all the experimental period, few pyknotic cells or TUNEL-positive cells were observed in the VZ/SVZ of the telencephalic wall and striatum in the control group. On the other hand, in the VZ/SVZ of the telencephalic wall and striatum in the MTX group, pyknotic cells or TUNEL-positive cells were observed on GD 17, and they increased significantly on GD18 and then decreased to the control levels from GD 19 onward. The phospho-Histone H3-positive rate decreased remarkedly in the VZ/SVZ of the telencephalic wall and striatum of the MTX group on GDs 17 and 18, compared to the control group, but they recovered on and after GD 19. These results suggested that there was a high possibility that development of the telencephalon in this period required strong folic acid. PMID- 26369367 TI - A novel fibrinogenase from Agkistrodon acutus venom protects against LPS-induced endotoxemia via regulating NF-kappaB pathway. AB - CONTEXT: Endotoxins including lipopolysaccharide (LPS) could cause endotoxemia which often results in excessive inflammation, organ dysfunction, sepsis, disseminated intravascular coagulation (DIC) or even death. Previously, a novel fibrinogenase (FII) showed protective effects on LPS-induced DIC via activating protein C and suppressing inflammatory cytokines. OBJECTIVE: To evaluate whether FII has protective effect on LPS-induced endotoxemia in mice and learn about the role of NF-kappaB pathway in TNF-alpha producing process. METHODS: BALB/C mice were intraperitoneally injected (i.p.) with (a) 30 mg/kg LPS, (b) LPS + 0.3 mg/kg FII, (c) LPS + 1.0 mg/kg FII, (d) LPS + 3.0 mg/kg FII or (e) saline. Both survival rate and organ function were tested, including alanine aminotransferase (ALT), blood urine nitrogen (BUN) and tissue section, and TNF-alpha was examined by ELISA. RAW 264.7 macrophage was administered with (a) LPS, (b) LPS + FII, (c) FII alone or (d) saline, and TNF-alpha and phosphorylation (P)-NF-kappaB (P65) were determined by Western blot. RESULTS: The administration of LPS led to 65% mortality rate, a rise of serum TNF-alpha, BUN and ALT levels, and both liver and renal tissue damage were observed. While FII treatment significantly increased the survival rate of LPS-induced endotoxemia mice model, histopathology and protein analysis results also revealed that FII remarkably protected liver and renal from LPS damage as well as decreasing TNF-alpha level. In vitro, FII significantly decreased LPS-induced TNF-alpha production and the expression of P NF-kappaB (P65). CONCLUSIONS: Our findings suggested that FII had protective effect on LPS-induced endotoxemia and organ injuries by suppressing the activation of NF-kappaB which decreased TNF-alpha level. PMID- 26369368 TI - Genomic intensive care: should we perform genome testing in critically ill newborns? PMID- 26369369 TI - Aspects of pulse oximetry screening for critical congenital heart defects: when, how and why? AB - Pulse oximetry (PO) screening for critical congenital heart defects (CCHD) has been studied extensively and is being increasingly implemented worldwide. This review provides an overview of all aspects of PO screening that need to be considered when introducing this methodology. PO screening for CCHD is effective, simple, quick, reliable, cost-effective and does not lead to extra burden for parents and caregivers. Test accuracy can be influenced by targets definition, gestational age, timing of screening and antenatal detection of CCHD. Early screening can lead to more false positive screenings, but has the potential to detect significant pathology earlier. There is no apparent difference in accuracy between screening with post-ductal measurements only, compared with screening using pre-ductal and post-ductal measurements. However, adding pre-ductal measurements identifies cases of CCHD which would have been missed by post-ductal screening. Screening at higher altitudes leads to more false positives. Important non-cardiac pathology is found in 35-74% of false positives in large studies. Screening is feasible in neonatal intensive care units and out-of-hospital births. Training caregivers, simplifying the algorithm and using computer-based interpretation tools can improve the quality of the screening. Caregivers need to consider all aspects of screening to enable them to choose an optimal protocol for implementation of CCHD screening in their specific setting. PMID- 26369370 TI - Outbreaks of extended spectrum beta-lactamase-producing Enterobacteriaceae in neonatal intensive care units: a systematic review. AB - OBJECTIVE: To establish the number of outbreaks of extended spectrum beta lactamase (ESBL) producing organisms in neonatal intensive care units (NICUs), to determine causes, mortality rates, proportions of infants colonised and infected and the interventions that terminated outbreaks. METHODS: A systematic review of the literature in English, Spanish and French was undertaken with searches in four databases. The review conformed to the PRISMA guidelines, and the data extraction was modelled on the ORION criteria for studies of nosocomial infection. RESULTS: 75 studies fulfilled the inclusion criteria. There were 1185 cases of colonisation, 860 infections and 139 deaths. The median outbreak duration was 6.2 months (IQR 2.0-7.5 months). Klebsiella pneumoniae was the most frequently implicated pathogen. Understaffing was the most frequent risk factor for outbreaks. The most commonly identified source was admission of an ESBL colonised infant with subsequent horizontal dissemination. The main interventions described were improved infection-control procedures and screening of staff and the environment. 26 studies were included in the quantitative analysis. Random effects meta-analysis indicated high mortality rates in infants who developed infection (31%, 95% CI 20% to 43%). CONCLUSION: ESBL outbreaks in NICUs are associated with significant mortality and prolonged disruption. Understaffing is a major risk factor, but is infrequently addressed by interventions. Poor infection-control procedures are frequently implicated as contributing to ESBL spread. Better reporting of outbreaks may help clarify the role for routine ESBL screening in NICUs. PMID- 26369372 TI - Diversity-oriented synthesis of fused thioglycosyl benzo[e][1,4]oxathiepin-5-ones and benzo[f][1,4]thiazepin-5(2H)-ones by a sequence of palladium-catalyzed glycosyl thiol arylation and deprotection-lactonization reactions. AB - An efficient synthesis of thioglycosylated benzo[e][1,4]oxathiepin-5-one and benzothiazepinone derivatives by a sequence of palladium-catalyzed glycosyl thiol arylation followed by deprotection-lactonization reactions has been reported. This diversity-oriented strategy enabled access to unknown complex cyclic scaffolds with polyhydroxylated appendages of biological interest. PMID- 26369371 TI - Prenatal surgery for myelomeningocele and the need for cerebrospinal fluid shunt placement. AB - OBJECT: The Management of Myelomeningocele Study (MOMS) was a multicenter randomized trial comparing the safety and efficacy of prenatal and postnatal closure of myelomeningocele. The trial was stopped early because of the demonstrated efficacy of prenatal surgery, and outcomes on 158 of 183 pregnancies were reported. Here, the authors update the 1-year outcomes for the complete trial, analyze the primary and related outcomes, and evaluate whether specific prerandomization risk factors are associated with prenatal surgery benefit. METHODS: The primary outcome was a composite of fetal loss or any of the following: infant death, CSF shunt placement, or meeting the prespecified criteria for shunt placement. Primary outcome, actual shunt placement, and shunt revision rates for prenatal versus postnatal repair were compared. The shunt criteria were reassessed to determine which were most concordant with practice, and a new composite outcome was created from the primary outcome by replacing the original criteria for CSF shunt placement with the revised criteria. The authors used logistic regression to estimate whether there were interactions between the type of surgery and known prenatal risk factors (lesion level, gestational age, degree of hindbrain herniation, and ventricle size) for shunt placement, and to determine which factors were associated with shunting among those infants who underwent prenatal surgery. RESULTS: Ninety-one women were randomized to prenatal surgery and 92 to postnatal repair. The primary outcome occurred in 73% of infants in the prenatal surgery group and in 98% in the postnatal group (p < 0.0001). Actual rates of shunt placement were only 44% and 84% in the 2 groups, respectively (p < 0.0001). The authors revised the most commonly met criterion to require overt clinical signs of increased intracranial pressure, defined as split sutures, bulging fontanelle, or sunsetting eyes, in addition to increasing head circumference or hydrocephalus. Using these modified criteria, only 3 patients in each group met criteria but did not receive a shunt. For the revised composite outcome, there was a difference between the prenatal and postnatal surgery groups: 49.5% versus 87.0% (p < 0.0001). There was also a significant reduction in the number of children who had a shunt placed and then required a revision by 1 year of age in the prenatal group (15.4% vs 40.2%, relative risk 0.38 [95% CI 0.22-0.66]). In the prenatal surgery group, 20% of those with ventricle size < 10 mm at initial screening, 45.2% with ventricle size of 10 up to 15 mm, and 79.0% with ventricle size >= 15 mm received a shunt, whereas in the postnatal group, 79.4%, 86.0%, and 87.5%, respectively, received a shunt (p = 0.02). Lesion level and degree of hindbrain herniation appeared to have no effect on the eventual need for shunting (p = 0.19 and p = 0.13, respectively). Similar results were obtained for the revised outcome. CONCLUSIONS: Larger ventricles at initial screening are associated with an increased need for shunting among those undergoing fetal surgery for myelomeningocele. During prenatal counseling, care should be exercised in recommending prenatal surgery when the ventricles are 15 mm or larger because prenatal surgery does not appear to improve outcome in this group. The revised criteria may be useful as guidelines for treating hydrocephalus in this group. PMID- 26369373 TI - [Prediction of conversion from amnestic mild cognitive impairment to Alzheimer's disease using proton magnetic resonance spectroscopy]. AB - Amnestic mild cognitive impairment (aMCI) has been considered to be a transitional state between healthy aging and very mild Alzheimer's disease (AD). Most patients with aMCI convert to AD over time, but some of them remain stable as aMCI. In this study, 22 patients with aMCI underwent proton magnetic resonance spectroscopy (1H-MRS) of hippocampus and posterior cingulate cortex. Ten patients converted to AD had significantly lower N-acetylaspartate (NAA) concentrations in both hippocampi when compared to 12 patients remained stable to be aMCI. The mean NAA concentration of both hippocampi equal to or lower than 7.6 mmol/l predicted conversion to AD at 1.0 sensitivity and 1.0 specificity and the area under receiver operating curve (ROC) was 1.0. Absolute quantification of 1H-MRS of hippocampus seems to be a useful marker for predicting conversion to AD from patients with aMCI . PMID- 26369374 TI - [A case of Hashimoto's encephalopathy successfully treated with oral steroid therapy, resistant to high-dose methylprednisolone, plasma exchange and intravenous immunoglobulin]. AB - A 30-year-old woman was admitted to the first institution with subacutely progressive aphasia and depression. Despite of lacking conclusive evidence on magnetic resonance imaging, cerebrospinal fluid examination, or electroencephalogram, we tentatively diagnosed her disease as limbic encephalopathy due to its acute progression. High-dose methylprednisolone was started on admission. However, symptoms did not improve. To make matters worse, psychiatric symptoms, such as hallucinations and emotional incontinence, appeared on the same day. Additional treatment with plasma exchange and intravenous immunoglobulin administration was also ineffective. Therefore, we could not manage the patient in a general ward due to severe psychiatric symptoms. The patient was transferred to a psychiatric ward in the second institution. She received both psychiatric treatment and steroid therapy, including a second course of intravenous high-dose methylprednisolone, followed by long-term oral prednisolone. Her symptoms gradually improved. A final diagnosis of Hashimoto's encephalopathy was made based on the patient's clinical course and positive results for both serum anti-thyroid antibody and anti-NAE antibody. In our case, long-term oral steroid therapy under psychiatric treatment was effective for good outcome. PMID- 26369375 TI - [A case of tuberculous myeloradiculitis with abdominal lymphadenitis presenting with symptoms of radiculomyelopathy]. AB - A 30-year old man was admitted with right hip pain and gait disturbances. Neurological findings revealed muscular weakness in the lower limbs, hyporeflexia, dysesthesia in the sacral region, and bowel and bladder disturbances. Cerebrospinal fluid (CSF) examination indicated a white blood cell count of 371/MUl (lymphocyte:polymorphonuclear leukocyte = 97:3), protein levels of 463 mg/dl and sugar of 20 mg/dl. Although CSF culture was negative, tuberculous infection was presumed. Magnetic resonance imaging revealed areas of enhancement in the intramedullary region surrounding the spinal cord and cauda equina. Enhanced computed tomography (CT) of the abdomen revealed lymph node swelling around the head of the pancreas. Biopsy of the lymph node swelling was culture-positive for Mycobacterium tuberculosis. Hence, assuming a diagnosis of tuberculous lymphadenitis of the abdomen, antitubercular drugs were started. Since antitubercular therapy had beneficial effects on the neurological symptoms and CSF findings, we diagnosed the patient with tuberculous myeloradiculitis. Systematic examinations including lymph node biopsy and cultures were useful for the diagnosis of tuberculous myeloradiculitis. PMID- 26369376 TI - [A case of cholesterol embolization syndrome with cognitive impairment and pulmonary hemorrhage]. AB - A seventy-year-old man developed color change in his left toes and was treated for frostbite. Eight months later, he developed cognitive impairment and was admitted to our hospital. A remarkable increase of eosinophils was observed in peripheral blood. Brain MRI revealed abnormal lesions in the fornix, corpus callosum, basal ganglia and frontal lobe. Steroid therapy ameliorated his symptom temporarily, but he suddenly developed cardiopulmonary arrest. His autopsy revealed severe pulmonary hemorrhage with alveolar vasculitis and cholesterol crystals in the brain, kidneys, liver, and the other organs. It was possible that cholesterol embolization to multiple organs including the brain induced systemic vasculitis that caused pulmonary hemorrhage and his critical prognosis. Cholesterol embolization should be considered when we see a patient with brain lesions accompanied with eosinophilia. PMID- 26369377 TI - [Simultanagnosia and scene agnosia induced by right posterior cerebral artery infarction: a case report]. AB - A 68-year-old man was admitted to our hospital for rehabilitation of topographical disorientation. Brain magnetic resonance imaging revealed infarction in the right medial side of the occipital lobe. On neuropsychological testing, he scored low for the visual information-processing task; however, his overall cognitive function was retained. He could identify parts of the picture while describing the context picture of the Visual Perception Test for Agnosia but could not explain the contents of the entire picture, representing so-called simultanagnosia. Further, he could morphologically perceive both familiar and new scenes, but could not identify them, representing so-called scene agnosia. We report this case because simultanagnosia associated with a right occipital lobe lesion is rare. PMID- 26369378 TI - [Clinical characteristics of four patients with temporal lobe epilepsy associated with elevated anti-GAD antibodies]. AB - Anti-glutamic acid decarboxylase (GAD) antibodies are known to be associated with insulin-dependent diabetes mellitus (IDDM), stiff-person syndrome, and other neurological symptoms including temporal lobe epilepsy (TLE), known as autoimmune epilepsy. We treated four patients with TLE who had elevated titers of serum anti GAD antibody (anti-GAD-Ab), higher than 100 U/ml. Three of the four patients started to have epileptic seizures in their 5th or 6th decade. Characteristic symptoms suggesting encephalitis or encephalopathy were absent at onset of these symptoms, which led to delayed diagnosis. All four patients developed two or three of cerebellar ataxia, neuropsychological impairment, and IDDM, by several years or decades after onset of TLE, even after seizure freedom in two patients. These abnormalities were indicators for suspecting the involvement of anti-GAD-Ab in the pathogenesis. Anti-GAD-Ab levels in the cerebrospinal fluid (CSF) were measured, which detected elevated CSF/serum anti-GAD-Ab ratio (>= 1.0), suggesting intrathecal anti-GAD-Ab synthesis, in three of the four patients. The TLE symptoms were somewhat prolonged, but three of the four patients eventually achieved seizure freedom after immunotherapies with combinations of two or three anti-epileptic drugs. Serum anti-GAD Ab is recommended to be measured in patients with middle-aged onset TLE. Moreover, immune-modulating therapies including steroid pulse and intravenous immunoglobulin therapies could have ameliorated neurological complications, even in the chronic phase. PMID- 26369379 TI - Nitrogen heterocyclic carbene containing pentacoordinate iron dicarbonyl as a [Fe]-hydrogenase active site model. AB - A novel pentacoordinate mono iron dicarbonyl complex bearing a nitrogen heterocyclic carbene ligand was reported as a model of a [Fe]-hydrogenase active site, which exhibits interesting proton coupled CO binding reactivity, electro catalytic proton reduction and catalytic transfer hydrogenation reactivity. PMID- 26369380 TI - Dietary flavonoids, lignans and colorectal cancer prognosis. AB - Flavonoids and lignans are polyphenol classes with anticarcinogenic activities against colorectal cancer (CRC). However, very limited epidemiological evidence exists on their effects on CRC prognosis. This study aimed to evaluate the association between flavonoid and lignan intakes with the risk of CRC recurrence and overall survival in CRC patients. The study followed incident histologically confirmed CRC cases in Barcelona (Spain). Validated dietary questionnaires and lifestyle information were collected at recruitment. An ad hoc food composition database on flavonoids and lignans was compiled by using data from the US Department of Agriculture and Phenol-Explorer databases. Adjusted hazards ratios (HR) and 95% confidence intervals (CIs) were estimated using multivariable Cox models. After 8.6 years of mean follow-up, 133 of 409 (32.5%) participants died and 77 of 319 (24.1%) had a CRC recurrence. Total flavonoids were associated neither with CRC recurrence (HR comparing extreme tertiles 1.13, 95% CI 0.64 2.02; P-trend 0.67) nor with overall survival (HR(T3vsT1) 1.06, 95% CI 0.69-1.65; P-trend 0.78) in the multivariable models. No associations were also observed with either total lignans or any flavonoid subclass intake. In conclusion, the results of the current study do not support a role of flavonoid and lignan intake in the CRC prognosis. PMID- 26369381 TI - Reply to comments on the review article 'Time trends in the incidence and prevalence of multiple sclerosis in Norway during eight decades'. PMID- 26369382 TI - Elevated second-trimester maternal serum beta-human chorionic gonadotropin and amniotic fluid alpha-fetoprotein as indicators of adverse obstetric outcomes in fetal Turner syndrome. AB - AIM: The objective of this study was to determine the ability of biochemical analytes to identify adverse outcomes in pregnancies with Turner syndrome. METHODS: Maternal serum and amniotic fluid (AF) marker concentrations were measured in 73 singleton pregnancies with Turner syndrome (10-22 weeks of gestation). Fetal Turner syndrome was definitively established by cytogenetic analysis. Two subgroups, fetuses with hydrops fetalis versus fetuses with cystic hygroma, were compared. Receiver operating characteristic curves and relative risk were established for a cut-off multiples of the median >=3.5 for beta subunit of human chorionic gonadotropin (hCG) or AF alpha-fetoprotein (AFP). RESULTS: Forty-nine (67%) of 73 pregnant women had an abnormal maternal serum. While levels of pregnancy-associated plasma protein-A and free beta-subunit (fbeta)-hCG were not different to those of the control group, AFP, unconjugated estriol and beta-hCG concentrations were significantly different in the study group (P < 0.05), when compared to those of unaffected pregnancies. Levels of beta-hCG in pregnancies with hydrops fetalis were significantly higher than in those with cystic hygroma (P <0.0001), as were AF-AFP concentrations (P <0.0015). In addition, abnormalities in both maternal serum beta-hCG and AF-AFP predicted fetal death. The relative risk of adverse obstetric outcome was 10.667 (P = 0.0004; 95% confidence interval [CI]: 1.554-73.203) for beta-hCG and 2.19 (P = 0.0256; 95% CI: 1.001 to 4.779), for AF-AFP. CONCLUSION: Maternal serum beta-hCG and AF-AFP levels may preferentially identify those Turner syndrome pregnancies with the highest risk of fetal death. PMID- 26369383 TI - Non-invasive screening of diabetics in primary care for NAFLD and advanced fibrosis by MRI and MRE. AB - BACKGROUND: Current guidelines do not recommend screening for non-alcoholic fatty liver disease (NAFLD) or advanced fibrosis. Patients with type 2 diabetes mellitus (T2DM) are known to be at increased risk for NAFLD and advanced fibrosis. AIM: To assess the feasibility in diabetics in a primary care setting of screening for NAFLD and advanced fibrosis, by using non-invasive magnetic resonance imaging (MRI) to estimate the hepatic proton density fat fraction (MRI PDFF) and magnetic resonance elastography (MRE) to estimate hepatic stiffness. METHODS: We performed a cross-sectional analysis of a prospective study that included 100 (53% men) consecutively enrolled diabetics who did not have any other aetiology of liver disease. All patients underwent a standardised research visit, laboratory tests, MRI-PDFF, and MRE. RESULTS: Mean (+/-s.d.) age and body mass index (BMI) was 59.7 (+/-11.2) years and 30.8 (+/-6.5) kg/m(2) , respectively. The prevalence of NAFLD (defined as MRI-PDFF >=5%) and advanced fibrosis (defined as MRE >=3.6 kPa) was 65% and 7.1%, respectively. One patient with advanced fibrosis had definite hepatocellular carcinoma. When compared to those without NAFLD, patients with NAFLD were younger (P = 0.028) and had higher mean BMI (P = 0.0008), waist circumference (P < 0.0001) and prevalence of metabolic syndrome (84.6% vs. 40.0%, P < 0.0001). Only 26% of those with NAFLD had elevated alanine aminotransferase. CONCLUSIONS: This proof-of-concept study demonstrates that T2DM has significant rates of both NAFLD and advanced fibrosis. Concomitant screening for NAFLD and advanced fibrosis by using MRI-proton density fat fraction and magnetic resonance elastography in T2DM is feasible and may be considered after validation in a larger cohort. PMID- 26369384 TI - SENP2 regulates MMP13 expression in a bladder cancer cell line through SUMOylation of TBL1/TBLR1. AB - Bladder cancer (BC) is the most popular malignant urinary cancer in China. BC has the highest incidence and mortality among all genitourinary system tumors. Although the early-stage BC could be treated with advanced electron flexible systourethroscope, early metastasis of the BC occur frequently, and often results in poor prognosis. Recently, we reported that small ubiquitin related modifier (SUMO)-specific protease 2 (SENP2) was downregulated in BC specimen. SENP2 appeared to inhibit migration and invasion of bladder cancer cells in vitro, through suppressing MMP13 in BC cells. However, the exact underlying mechanisms remain unknown. Here, we reported that SENP2 inhibited nuclear translocation of beta-catenin, which targeted the promotor of MMP13 to activate MMP13 to enhance BC cell metastasis. WNT ligands induced TBL1/TBLR1 SUMOylation to form complexes with beta-catenin to facilitate beta-catenin nuclear translocation, which could be efficiently inhibited through suppression of SUMOylation of TBL1/TBLR1. Together, our data suggest that SENP2 inhibits MMP13 expression in BC cells through de-SUMOylation of TBL1/TBLR1, which inhibits nuclear translocation of beta-catenin. Thus, SENP2 may be a promising therapeutic target for BC. PMID- 26369385 TI - Is type 2 hepatorenal syndrome still a potential indication for treatment with terlipressin and albumin? PMID- 26369387 TI - Short-term low-intensity blood flow restricted interval training improves both aerobic fitness and muscle strength. AB - The present study aimed to analyze and compare the effects of four different interval-training protocols on aerobic fitness and muscle strength. Thirty-seven subjects (23.8 +/- 4 years; 171.7 +/- 9.5 cm; 70 +/- 11 kg) were assigned to one of four groups: low-intensity interval training with (BFR, n = 10) or without (LOW, n = 7) blood flow restriction, high-intensity interval training (HIT, n = 10), and combined HIT and BFR (BFR + HIT, n = 10, every session performed 50% as BFR and 50% as HIT). Before and after 4 weeks training (3 days a week), the maximal oxygen uptake (VO2max ), maximal power output (Pmax ), onset blood lactate accumulation (OBLA), and muscle strength were measured for all subjects. All training groups were able to improve OBLA (BFR, 16%; HIT, 25%; HIT + BFR, 22%; LOW, 6%), with no difference between groups. However, VO2max and Pmax improved only for BFR (6%, 12%), HIT (9%, 15%) and HIT + BFR (6%, 11%), with no difference between groups. Muscle strength gains were only observed after BFR training (11%). This study demonstrates the advantage of short-term low-intensity interval BFR training as the single mode of training able to simultaneously improve aerobic fitness and muscular strength. PMID- 26369389 TI - Decade in review--acute kidney injury: Acute kidney injury--a decade of progress. PMID- 26369386 TI - Differential genomic imprinting regulates paracrine and autocrine roles of IGF2 in mouse adult neurogenesis. AB - Genomic imprinting is implicated in the control of gene dosage in neurogenic niches. Here we address the importance of Igf2 imprinting for murine adult neurogenesis in the subventricular zone (SVZ) and in the subgranular zone (SGZ) of the hippocampus in vivo. In the SVZ, paracrine IGF2 is a cerebrospinal fluid and endothelial-derived neurogenic factor requiring biallelic expression, with mutants having reduced activation of the stem cell pool and impaired olfactory bulb neurogenesis. In contrast, Igf2 is imprinted in the hippocampus acting as an autocrine factor expressed in neural stem cells (NSCs) solely from the paternal allele. Conditional mutagenesis of Igf2 in blood vessels confirms that endothelial-derived IGF2 contributes to NSC maintenance in SVZ but not in the SGZ, and that this is regulated by the biallelic expression of IGF2 in the vascular compartment. Our findings indicate that a regulatory decision to imprint or not is a functionally important mechanism of transcriptional dosage control in adult neurogenesis. PMID- 26369392 TI - Decade in review--glomerular disease: The glomerulus reveals some secrets. PMID- 26369394 TI - Acceptance and commitment therapy group-treatment for non-responsive patients with personality disorders: An exploratory study. AB - Patients with personality disorders who did not respond to previous outpatient treatment are among the most challenging patients to treat and are often referred to specialized settings. Acceptance and commitment therapy (ACT) is an innovative therapy that has shown effectiveness in treatment-resistant cases with chronic or recurrent depression with or without co-morbid personality disorders. The central role that ACT accords to positive values and experiential avoidance may enhance treatment responsivity in patients with personality disorders that did not respond to previous treatments. The current nonrandomized study explored the effectiveness of a 26-week ACT-based group treatment (n = 60) for personality disorders compared to treatment-as-usual (n = 21) based on cognitive behaviour therapy (CBT-TAU) at a specialized setting for patients with personality disorders. Individuals in both treatment conditions demonstrated small to moderate decreases in general psychological functioning and personality pathology. There was no main effect of therapy condition. Overall, results suggest that ACT is a possible treatment option for individuals with difficult-to treat personality pathology and further outcome research is warranted. PMID- 26369395 TI - Regeneration-associated genes decline in chronically injured rat sciatic motoneurons. AB - Chronic nerve injuries are notorious for their poor regenerative outcomes. Here, we addressed the question of whether the established reduced ability of injured motoneurons to regenerate their axons with time of disconnection with targets (chronic axotomy) is associated with a failure of injured motoneurons to express and sustain their expression of regeneration-associated genes. Sciatic motoneurons were prevented from regenerating by ligation of the transected nerves (chronic axotomy), and then subjected to a second nerve transection (acute axotomy) to mimic the clinical surgical procedure of refreshing the proximal nerve stump prior to delayed nerve repair. The expression of alpha1-tubulin, actin and GAP-43 mRNA was analysed in axotomized sciatic motoneurons by the use of in situ hybridization followed by autoradiography and silver grain quantification. The expression of these regeneration-associated genes by naive (acutely) axotomized motoneurons declined exponentially, to reach baseline levels within 6 months. These chronically injured motoneurons responded to a refreshment axotomy by elevating the expression of the genes to the same levels as in acutely (i.e. for the first time) axotomized sciatic motoneurons. However, the expression of these declined more rapidly than after acute axotomy. We conclude that a progressive decline in the expression of the regeneration-associated genes in chronically axotomized motoneurons and the even more rapid decline in their expression in response to a refreshment axotomy may explain why the regenerative capacity of chronically axotomized neurons declines with time. PMID- 26369396 TI - Drug survival of methotrexate treatment in hand eczema patients: results from a retrospective daily practice study. PMID- 26369397 TI - Adenovirus-mediated delivery of Factor H attenuates complement C3 induced pathology in the murine retina: a potential gene therapy for age-related macular degeneration. AB - BACKGROUND: Age-related macular degeneration (AMD) is the most common cause of blindness in the elderly, with no therapy available for 90% of patients. Recent genetic evidence implicates activation of complement in the pathogenesis of AMD. We have recently discovered that adenovirus (Ad)-mediated expression of complement component C3 (AdCMVC3) in the murine retina recapitulates many of the pathological features found in human AMD. In the present study, utilizing a gene therapy approach, we examine whether Ad-mediated expression of complement Factor H (AdCAGfH) attenuates AdCMVC3-mediated retinal pathology. METHODS: AdCMVC3 was co-injected with either AdCAGfH or a negative control virus expressing green fluorescent protein (AdCMVGFP) into the subretinal space of adult mice. The resulting retinal pathology was analyzed by histology and immunocytochemistry and retinal function was quantified by electroretinography. RESULTS: Morphological and functional analyses indicated that AdCMVC3-mediated retinal pathology could be attenuated by AdCAGfH. Specifically, endothelial cell proliferation was reduced by 91% and atrophy of retinal pigment epithelium (RPE) could be attenuated by 69%. AdCAGfH injected eyes exhibited 90-150% greater A-wave and 120 180% greater B-wave amplitudes relative to control eyes. Immunocytochemical analysis of rhodopsin and RPE65 was consistent with the rescue of photoreceptors and RPE in AdCAGfH injected eyes. CONCLUSIONS: C3-induced pathology in murine retina can be attenuated by Ad-mediated expression of Factor H. Expression of Factor H is worthy of further study as a potential gene therapy for AMD. PMID- 26369398 TI - Predictive formula for acute liver failure is useful for predicting the prognosis of patients with acute-on-chronic liver failure. AB - AIM: The prognosis of acute-on-chronic liver failure (ACLF) is extremely poor in comparison to acute liver failure (ALF). We aimed to establish methods for the early diagnosis of ACLF and its severity to identify the patients with a poor prognosis. METHODS: The laboratory data at admission of 30 ACLF and 46 ALF patients were compared. Three established prognosis prediction models (Model for End-Stage Liver Disease [MELD]; MELD modified by serum sodium concentration, [MELD-Na]; and the Japan hepatic encephalopathy prediction model [J-HEPM]) were assessed using area under the receiver-operator curve (AUROC) values. RESULTS: No significant difference was found in the laboratory data of the two patient groups. J-HEPM was able to predict the outcome of the ACLF subjects (AUROC = 0.93). CONCLUSION: Although ACLF could not be differentially diagnosed from ALF at admission from the laboratory data alone, the J-HEPM effectively predicted the prognosis of liver failure in patients with ACLF. These findings indicate that ACLF patients with high J-HEPM scores require earlier and more intensive care than ALF patients. PMID- 26369399 TI - Congenital 'de novo' malignant melanoma. Successful surgical approach in a Bulgarian newborn. PMID- 26369400 TI - Phylogenetic analysis of human group C rotavirus in hospitalized children with gastroenteritis in Belem, Brazil. AB - Group C rotavirus (RVC) is potentially an important pathogen associated with acute gastroenteritis (AG), especially in outbreaks. This study aims to detect and molecularly characterize RVC in hospitalized children with AG in Belem, Brazil. From May 2008 to April 2011, 279 stools were subjected to reverse transcription polymerase chain reaction targeting VP7, VP6, VP4, and NSP4 genes. RVC positivity rate was 2.1% (6/279) and phylogenetic analysis of positive samples yields genotype G4-P[2]-I2-E2. No evidence of zoonotic transmission and VP7 gene demonstrated close relationship with Asian strains. RVC surveillance is worth to expand information on evolutionary and epidemiological features of this virus. PMID- 26369401 TI - Does vagotomy reduce the risk of Parkinson's disease: The authors reply. PMID- 26369402 TI - Canine epidermolysis bullosa acquisita: a retrospective study of 20 cases. AB - BACKGROUND: Epidermolysis bullosa acquisita (EBA) is a rare autoimmune subepidermal blistering disease of dogs and humans. OBJECTIVES: Our objectives were to describe clinical phenotypes, histopathology and treatment outcomes of canine EBA. ANIMALS: Twenty dogs diagnosed with EBA based on a subepidermal blister formation and collagen VII autoreactivity. RESULTS: Most dogs were young (median: 1.2-year-old) with a male-to-female ratio of 2.3:1. Nine of 20 dogs (45%) developed lesions before one year of age and 11 of 20 dogs (55%) were great danes. Tense vesicles and bullae (18 of 20; 90%) and deep erosions and ulcers (20 of 20; 100%) were the most common lesions and these affected predominantly the oral cavity (19 of 20; 95%), pinnae (16 of 20; 80%), axillae (15 of 20; 75%) and footpads (14 of 20; 70%). Histopathology identified neutrophilic perivascular dermatitis (17 of 17; 100%) without or with (12 of 17; 71%) eosinophils, which occasionally equalled (four cases) or outnumbered neutrophils (two cases). Subepidermal vesicles were either devoid of inflammation or contained neutrophils with or without eosinophils, fibrin and/or haemorrhage. A complete remission of skin lesions was obtained in 14 dogs with a median time of 58 days. Glucocorticoids were used in these dogs either as a monotherapy (3 of 14; 21%) or in combination with other immunomodulating drugs (11 of 14; 79%). The median dose of prednisone was 3 mg/kg/day. The remaining six dogs were euthanized. CONCLUSIONS AND CLINICAL IMPORTANCE: Canine EBA is a rare subepidermal blistering disease with an inflammatory phenotype and a predilection for young great danes and male dogs. The outcome of treatment appears more favourable than assumed previously. PMID- 26369403 TI - The antagonistic effect of Banana bunchy top virus multifunctional protein B4 against Fusarium oxysporum. AB - The viral-induced banana bunchy top disease and the fungal-induced banana blight are two major causes of concern for industrial scale production of bananas. Banana blight is particularly troublesome, affecting ~80% of crops worldwide. Strict guidelines and protocols are in place in order to ameliorate the effects of this devastating disease, yet little success has been achieved. From the data presented here, we have found that Banana bunchy top virus (BBTV)-infected bananas are more resistant to Fusarium oxysporum f. sp. cubense (Foc). BBTV appears to be antagonistic towards Foc, thus improving the survivability of plants against blight. The BBTV suppressor of RNA silencing, namely protein B4, displays fungicidal properties in vitro. Furthermore, transgenic tomatoes expressing green fluorescent protein (GFP)-tagged protein B4 demonstrate enhanced resistance to F. oxysporum f. sp. lycopersici (Fol). Differential gene expression analysis indicates that increased numbers of photogenesis-related gene transcripts are present in dark-green leaves of B4-GFP-modified tomato plants relative to those found in WT plants. Conversely, the transcript abundance of immunity-related genes is substantially lower in transgenic tomatoes compared with WT plants, suggesting that plant defences may be influenced by protein B4. This viral-fungal interaction provides new insights into microbial community dynamics within a single host and has potential commercial value for the breeding of transgenic resistance to Fusarium-related blight/wilt. PMID- 26369404 TI - Homology modeling and in silico site directed mutagenesis of pyruvate ferredoxin oxidoreductase from Clostridium thermocellum. AB - Pyruvate ferredoxin oxidoreductase is the crucial enzyme that involves in bioethanol synthesis pathway of Clostridium thermocellum. It is an ethanologenic organism but has been investigated less on its enzyme structure. The amino acid sequence of Pyruvate ferredoxin oxidoreductase was derived from UNIPROT and the screened crystal structure was taken as the template for homology modeling using MODELLER 9V11. The model was loop refined and was validated using RMSD, ProSA and PROCHECK. The docking and per residue interaction studies were carried out to elucidate the interaction energies of amino acid residues with pyruvate. To enhance the binding of pyruvate with the enzyme, mutation studies were carried out by replacing Thr31 as it had a less interaction energy. Out of 10 mutants, T31N, T31Q and T31G were selected using potential energy and the residual energy calculations. Five nanoseconds explicit MD simulations were run for apo, wild type and mutants T31N, T31Q and T31G using Desmond. RMSD, RMSF, distance plots and H-bonds analysis proved T31G to be a favorable mutant for binding of pyruvate. Thus, modeling PFOR would help in profound understanding of its structural clefts and mutation studies would aid in improving the enzyme efficiency. PMID- 26369405 TI - Synthesis, antitumor activity, and structure-activity relationship of some benzo[a]pyrano[2,3-c]phenazine derivatives. AB - A series of benzo[a]pyrano[2,3-c]phenazine derivatives with a wide range of substitutions at ring C of the benzophenazine were designed and synthesized using the one-pot, four-component domino reactions. The targeted compounds were evaluated for their antitumor activities against HCT116, MCF7, HepG2 and A549 cancer cell lines in vitro. The most active compound 6{1,2,1,9} featured the CN and p-dimethylamino phenyl substituents on gamma-pyran structure on ring C. Significantly, compound 6{1,2,1,9} was found to have the highest growth inhibitory activity against the HepG2 cell line with IC50 values of 6.71 uM, which was 1.6-fold more potent than positive control anticancer drug Hydroxycamptothecine (HCPT). Furthermore, structure-activity relationship (SAR) studies on the substitutions at ring C were discussed in details. PMID- 26369406 TI - Green approach to stereoselective synthesis of benzo[d]chromeno[3,4- h]oxathiazonine derivatives via MCRs in water: a combined experimental and DFT study. AB - (7S, 14S, 16R)- dialkyl 6-oxo-6,7,13,14-tetrahydro-7,14 methanobenzo[d]chromeno[3,4- h][1,6,3]oxathiazo-nine-14,16-dicarboxylates 4 and (S)-methyl 2-(2-methoxy-2-oxoethyl)-2,3- dihydrobenzo[d]thiazole-2-carboxylates 5 were readily synthesized in a ratio 3:1 and moderated yield by multicomponent reactions of 4-hydroxycoumarin and acetylenic esters with benzothiazole without using a catalyst. Also, The GIAO/DFT approach at the B3LYP/6-31G** level of theory was used to calculate the (1)H, (15)N, (17)O and (13)C NMR chemical shifts of product 4b. These computations are performed on the basis of X-ray structural data which are collected at 120(2) K temperature. In order to take into account intermolecular hydrogen bonds and the van der Waals effects, two different sizes of clusters (two model of trimeric and pentameric clusters) have been considered. A comparison between the experimental (Exp.) and calculated (Cal.) (1)H and (13)C NMR chemical shifts may reveal that the solution contains monomer, trimer1, trimer2, and pentamer models. PMID- 26369407 TI - The role of 18F-FDG uptake features in the differential diagnosis of solitary pulmonary lesions with PET/CT. AB - BACKGROUND: The aim of this study is to evaluate the value of (18)F-FDG uptake features in the diagnosis of solitary pulmonary lesions. METHODS: One hundred thirty-nine patients with solitary pulmonary lesions were divided into full uptake, circular uptake, multi-focus uptake, mild uptake, and no-uptake groups according to the uptake features of (18)F-FDG in solitary pulmonary lesions. The incidence of benign and malignant lesions and the false-positive and false negative rates in each group were analyzed. The sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of the method using (18)F-FDG uptake features combined with maximum standard uptake value (SUVmax) (SUV method) in the differential diagnosis of solitary pulmonary lesions were evaluated. RESULTS: There were 89 malignant and 50 benign lesions. (1) The malignant incidence of the full uptake group was 84.0% (63/75), and there were significant differences when compared with the other groups except the circular uptake group (16/23) (all P = 0.0001). The benign incidence of the multi focus and no-uptake groups was 83.3% (10/12) and 82.4% (14/17), respectively, and there were significant differences when compared with the full uptake and the circular uptake groups, respectively (all P < 0.05). The benign incidence of the mild uptake group was 58.3% (7/12), and there were no significant differences when compared with the others except the full uptake group (all P > 0.05). No statistical significance was found between either two of the no-uptake, mild uptake, and multi-focus uptake groups (all P > 0.05). (2) In cases with SUVmax >=2.5, the false-positive rate in the multi-focus uptake group was 83.3% (10/12), which was significantly higher than in the full uptake (12/75) or circular uptake group (7/23) (all P < 0.05). In cases with SUVmax <2.5, the false-negative rates in the mild and no-uptake groups were 41.7 and 17.6% (P = 0.218). (3) The sensitivity, specificity, accuracy, PPV, and NPV of the method using (18)F-FDG uptake features combined with SUVmax and the single SUV method were 88.7%/91.0%, 62.0%/42.0%, 79.1%/73.4%, 80.6%/73.6%, and 75.6%/72.4%, respectively. CONCLUSIONS: The method using uptake features of (18)F-FDG combined with SUVmax can improve the diagnostic specificity and accuracy of solitary pulmonary lesions. The multi-focus uptake feature maybe a benign sign, which still needs more researches to confirm. PMID- 26369408 TI - Serotonin 5-HT7 receptor agonist, LP-211, exacerbates Na(+), K(+)-ATPase/Mg(2+) ATPase imbalances in spinal cord-injured male rats. AB - BACKGROUND: The observed controversy that N-(4-cyanophenylmethyl)-4-(2-diphenyl) 1-piperazinehexanamide (LP-211), a selective serotonin (5-HT7) receptor agonist, may either modify or exacerbate imbalances in serum electrolyte concentrations and renal tissue of spinal cord trauma cases has not been reported yet. The aim of this study was to better understand the effects of a new 5-HT7 receptor agonist, LP-211, on serum electrolyte changes in spinal cord injured- (SCI) rats. METHODS: Sixty male rats were assigned to the following groups: A) Intact (saline as vehicle, 1 ml/kg, i.p.), B) Intact [LP-211, (0.003-0.3 mg/kg, i.p.)], C) Sham operated [laminectomy + vehicle (1 ml/kg, i.p.)], D) Sham-operated [laminectomy + LP-211 (0.003-0.3 mg/kg, i.p.)], E) Treatment [laminectomy + spinal trauma (SCI) + vehicle (1 ml/kg, i.p.)], F) Treatment [laminectomy + spinal trauma + LP-211 (0.003-0.3 mg/kg, i.p.)]. SCI was performed by placing an aneurysm clip, extradurally at the level of T10. After two weeks, LP-211 was administered cumulatively and each dose was injected (i.p.) with 20 min interval. At the end of the experiment, blood samples were collected for biochemical evaluations of the electrolytes employing standard commercial kits. RESULTS: The present results indicate elevated serum levels of Na(+), K(+), and Mg(2+) in SCI rats and significant differences demonstrated between the groups [P < 0.001, F(5, 35) = 23.92], [P < 0.001, F(5, 35) = 67.63], [P < 0.001, F(5, 35) = 71.144], respectively. So that, in groups B, D and F, there was a significant increase in K(+) and Mg(2+) serum levels compared to the groups A, C, and E (P < 0.001). Furthermore, Na(+) serum levels in SCI (LP-211), laminectomy (LP-211), and intact (LP-211) groups tended to be statistically lower than SCI (saline), laminectomy (saline) and intact (saline) groups. Infact, hyponatremia, hyperkalemia and hypermagnesemia was obtained in group F. Nevertheless, in the remaining measured serum electrolytes such as calcium (Ca(2+)), iron (Fe(2+)) and phosphorus (P(3 )), chlorine (Cl(-)), copper (Cu(+)), and zinc (Zu(+)), no significant changes were observed. CONCLUSION: It was shown that acute additive LP-211 treatments in the SCI group led to hyponatremia, hyperkalemia and hypermagnesemia, it may be stated that LP-211 treatment as a promising candidate for treating SCI complications in some systems especially urinary tract might take into consideration and further studies would be needed to clarify its benefits or drawbacks. The observed discrepancies, nevertheless; will also pose new questions. Altogether, this will ultimately contribute to further understanding the pathophysiological role regarding 5-HT7 receptor activation. PMID- 26369409 TI - Inhaled nitric oxide improves transpulmonary blood flow and clinical outcomes after prolonged cardiac arrest: a large animal study. AB - INTRODUCTION: The probability to achieve a return of spontaneous circulation (ROSC) after cardiac arrest can be improved by optimizing circulation during cardiopulomonary resuscitation using a percutaneous left ventricular assist device (iCPR). Inhaled nitric oxide may facilitate transpulmonary blood flow during iCPR and may therefore improve organ perfusion and outcome. METHODS: Ventricular fibrillation was electrically induced in 20 anesthetized male pigs. Animals were left untreated for 10 minutes before iCPR was attempted. Subjects received either 20 ppm of inhaled nitric oxide (iNO, n = 10) or 0 ppm iNO (Control, n = 10), simultaneously started with iCPR until 5 hours following ROSC. Animals were weaned from the respirator and followed up for five days using overall performance categories (OPC) and a spatial memory task. On day six, all animals were anesthetized again, and brains were harvested for neurohistopathologic evaluation. RESULTS: All animals in both groups achieved ROSC. Administration of iNO markedly increased iCPR flow during CPR (iNO: 1.81 +/ 0.30 vs CONTROL: 1.64 +/- 0.51 L/min, p < 0.001), leading to significantly higher coronary perfusion pressure (CPP) during the 6 minutes of CPR (25 +/- 13 vs 16 +/- 6 mmHg, p = 0.002). iNO-treated animals showed significantly lower S 100 serum levels thirty minutes post ROSC (0.26 +/- 0.09 vs 0.38 +/- 0.15 ng/mL, p = 0.048), as well as lower blood glucose levels 120-360 minutes following ROSC. Lower S-100 serum levels were reflected by superior clinical outcome of iNO treated animals as estimated with OPC (3 +/- 2 vs. 5 +/- 1, p = 0.036 on days 3 to 5). Three out of ten iNO-treated, but none of the CONTROL animals were able to successfully participate in the spatial memory task. Neurohistopathological examination of vulnerable cerebral structures revealed a trend towards less cerebral lesions in neocortex, archicortex, and striatum in iNO-treated animals compared to CONTROLs. CONCLUSIONS: In pigs resuscitated with mechanically assisted CPR from prolonged cardiac arrest, the administration of 20 ppm iNO during and following iCPR improved transpulmonary blood flow, leading to improved clinical neurological outcomes. PMID- 26369410 TI - The effect of performance-based financing on illness, care-seeking and treatment among children: an impact evaluation in Rwanda. AB - BACKGROUND: Performance-based financing (PBF) strategies are promoted as a supply side, results-based financing mechanism to improve primary health care. This study estimated the effects of Rwanda's PBF program on less-incentivized child health services and examined the differential program impact by household poverty. METHODS: Districts were allocated to intervention and comparison for PBF implementation in Rwanda. Using Demographic Health Survey data from 2005 to 2007 08, a community-level panel dataset of 5781 children less than 5 years of age from intervention and comparison districts was created. The impacts of PBF on reported childhood illness, facility care-seeking, and treatment received were estimated using a difference-in-differences model with community fixed effects. An interaction term between poverty and the program was estimated to identify the differential effect of PBF among children from poorer families. RESULTS: There was no measurable difference in estimated probability of reporting illness with diarrhea, fever or acute respiratory infections between the intervention and comparison groups. Seeking care at a facility for these illnesses increased over time, however no differential effect by PBF was seen. The estimated effect of PBF on receipt of treatment for poor children is 45 percentage points higher (p = 0.047) compared to the non-poor children seeking care for diarrhea or fever. CONCLUSIONS: PBF, a supply-side incentive program, improved the quality of treatment received by poor children conditional on patients seeking care, but it did not impact the propensity to seek care. These findings provide additional evidence that PBF incentivizes the critical role staff play in assuring quality services, but does little to influence consumer demand for these services. Efforts to improve child health need to address both supply and demand, with additional attention to barriers due to poverty if equity in service use is a concern. PMID- 26369411 TI - Erratum to: Investigating the mobilome in clinically important lineages of Enterococcus faecium and Enterococcus faecalis. PMID- 26369412 TI - Patient-Reported Outcomes Measurement Information System (PROMIS) instruments among individuals with symptomatic knee osteoarthritis: a cross-sectional study of floor/ceiling effects and construct validity. AB - BACKGROUND: The psychometric properties of Patient Reported Outcomes Measurement Information System (PROMIS) instruments have been explored in a number of general and clinical samples. No study, however, has evaluated the psychometric function of these measures in individuals with symptomatic knee osteoarthritis (KOA). The aim of this project was to evaluate the construct (structural) validity and floor/ceiling effects of four PROMIS measures in this population. METHODS: We conducted a secondary analysis of baseline data from a randomized trial comparing Tai Chi and physical therapy. Participants completed four PROMIS static short form instruments (i.e., Anxiety, Depression, Physical Function, and Pain Interference) as well as six well-validated (legacy) measures that assess pain, function, and psychological health. We calculated descriptive statistics and percentages of participants scoring the minimum (floor) and maximum (ceiling) possible scores for PROMIS and legacy measures. We also estimated the association between PROMIS scores and scores on legacy measures using Spearman's rank correlations coefficients. RESULTS: Data from 204 participants were analyzed. Mean age of the sample was 60 years; 70% were female. The PROMIS Anxiety and Depression had floor effects with 17 and 24% of participants scoring the minimum, respectively. PROMIS Anxiety and Depression scores had strongest associations with general mental health, including stress (Perceived Stress Scale, r >= 0.65) and depression (Beck Depression Index-II, r = 0.70). PROMIS Pain Interference scores correlated most strongly with measures of whole body pain (Short-Form 36 Bodily Pain, r = -0.73) and physical health (Short-Form 36 Physical-Component Summary, r = -0.73); their correlations were lower with other legacy measures, including with the WOMAC knee-specific pain (r = 0.47). PROMIS Physical Function scores had stronger associations with scores on the Short-Form 36 Physical Function (r = 0.79) than with scores on other legacy measures. CONCLUSION: The four PROMIS static-short forms performed well among individuals with symptomatic knee osteoarthritis as evidenced in correlations with legacy measures. PROMIS Anxiety and Depression target general mental health (e.g., stress, depression), and PROMIS Pain Interference and Physical Function static-short forms target whole-body outcomes among participants with symptomatic knee osteoarthritis. Floor effects in the PROMIS Anxiety and Depression scores should be considered if needing to distinguish among patients with very low levels of these outcomes. TRIAL REGISTRATION: Clinicaltrials.gov NCT01258985. Registered 10 December 2010. PMID- 26369413 TI - Metabolome analysis of 20 taxonomically related benzylisoquinoline alkaloid producing plants. AB - BACKGROUND: Recent progress toward the elucidation of benzylisoquinoline alkaloid (BIA) metabolism has focused on a small number of model plant species. Current understanding of BIA metabolism in plants such as opium poppy, which accumulates important pharmacological agents such as codeine and morphine, has relied on a combination of genomics and metabolomics to facilitate gene discovery. Metabolomics studies provide important insight into the primary biochemical networks underpinning specialized metabolism, and serve as a key resource for metabolic engineering, gene discovery, and elucidation of governing regulatory mechanisms. Beyond model plants, few broad-scope metabolomics reports are available for the vast number of plant species known to produce an estimated 2500 structurally diverse BIAs, many of which exhibit promising medicinal properties. RESULTS: We applied a multi-platform approach incorporating four different analytical methods to examine 20 non-model, BIA-accumulating plant species. Plants representing four families in the Ranunculales were chosen based on reported BIA content, taxonomic distribution and importance in modern/traditional medicine. One-dimensional (1)H NMR-based profiling quantified 91 metabolites and revealed significant species- and tissue-specific variation in sugar, amino acid and organic acid content. Mono- and disaccharide sugars were generally lower in roots and rhizomes compared with stems, and a variety of metabolites distinguished callus tissue from intact plant organs. Direct flow infusion tandem mass spectrometry provided a broad survey of 110 lipid derivatives including phosphatidylcholines and acylcarnitines, and high-performance liquid chromatography coupled with UV detection quantified 15 phenolic compounds including flavonoids, benzoic acid derivatives and hydroxycinnamic acids. Ultra performance liquid chromatography coupled with high-resolution Fourier transform mass spectrometry generated extensive mass lists for all species, which were mined for metabolites putatively corresponding to BIAs. Different alkaloids profiles, including both ubiquitous and potentially rare compounds, were observed. CONCLUSIONS: Extensive metabolite profiling combining multiple analytical platforms enabled a more complete picture of overall metabolism occurring in selected plant species. This study represents the first time a metabolomics approach has been applied to most of these species, despite their importance in modern and traditional medicine. Coupled with genomics data, these metabolomics resources serve as a key resource for the investigation of BIA biosynthesis in non-model plant species. PMID- 26369414 TI - A multilevel pan-cancer map links gene mutations to cancer hallmarks. AB - BACKGROUND: A central challenge in cancer research is to create models that bridge the gap between the molecular level on which interventions can be designed and the cellular and tissue levels on which the disease phenotypes are manifested. This study was undertaken to construct such a model from functional annotations and explore its use when integrated with large-scale cancer genomics data. METHODS: We created a map that connects genes to cancer hallmarks via signaling pathways. We projected gene mutation and focal copy number data from various cancer types onto this map. We performed statistical analyses to uncover mutually exclusive and co-occurring oncogenic aberrations within this topology. RESULTS: Our analysis showed that although the genetic fingerprint of tumor types could be very different, there were less variations at the level of hallmarks, consistent with the idea that different genetic alterations have similar functional outcomes. Additionally, we showed how the multilevel map could help to clarify the role of infrequently mutated genes, and we demonstrated that mutually exclusive gene mutations were more prevalent in pathways, whereas many co occurring gene mutations were associated with hallmark characteristics. CONCLUSIONS: Overlaying this map with gene mutation and focal copy number data from various cancer types makes it possible to investigate the similarities and differences between tumor samples systematically at the levels of not only genes but also pathways and hallmarks. PMID- 26369415 TI - Rare cardiac sequelae of a hump-nosed viper bite. AB - BACKGROUND: The hump-nosed pit viper (Hypnale hypnale) is the commonest cause for venomous snakebites in Sri Lanka. Previously, it was thought to cause only local envenomation. However recently, several systemic effects and even mortality has been reported. Along with other snakes, such as the Indian cobra (Naja naja), the common krait (Bungarus caeruleus), the Russell's viper (Daboia russelii) and the saw-scaled viper (Echis carinatus), the hump-nosed viper is now also considered capable of causing lethal envenomation. Unlike other snake species, the systemic manifestations occurring through the bite of a hump-nosed viper, such as acute renal failure, thrombotic microangiopathy etc are rare and unpredictable. CASE PRESENTATION: A 49-year-old Sri Lankan Tamil male presented with a hump-nosed viper bite, which had resulted in a cardiac arrest within half an hour of envenomation. On arrival to the Emergency Treatment Unit, he was unconscious and without spontaneous breathing. Electrocardiography monitoring revealed ST elevation in leads II, III and aVF with reciprocal changes in leads I and aVL indicating inferior wall infarction-as well as atrial fibrillation. Glasgow Coma Scale was 7/15, which indicated severe brain injury and electroencephalogram on day 10 revealed a low amplitude pattern compatible with diffuse brain damage. CONCLUSION: This case describes an authenticated case of myocardial infarction in a 49-year-old male following envenomation by a hump-nosed viper in Sri Lanka. This systemic effect of this viper's bite has not previously been described in the literature. This case report is intended to increase the vigilance for myocardial infarction following hump-nosed viper envenomation. PMID- 26369417 TI - Health care financing and the sustainability of health systems. AB - The economic crisis brought an unprecedented attention to the issue of health system sustainability in the developed world. The discussion, however, has been mainly limited to "traditional" issues of cost-effectiveness, quality of care, and, lately, patient involvement. Not enough attention has yet been paid to the issue of who pays and, more importantly, to the sustainability of financing. This fundamental concept in the economics of health policy needs to be reconsidered carefully. In a globalized economy, as the share of labor decreases relative to that of capital, wage income is increasingly insufficient to cover the rising cost of care. At the same time, as the cost of Social Health Insurance through employment contributions rises with medical costs, it imperils the competitiveness of the economy. These reasons explain why spreading health care cost to all factors of production through comprehensive National Health Insurance financed by progressive taxation of income from all sources, instead of employer employee contributions, protects health system objectives, especially during economic recessions, and ensures health system sustainability. PMID- 26369416 TI - Uridine supplementation exerts anti-inflammatory and anti-fibrotic effects in an animal model of pulmonary fibrosis. AB - RATIONALE: Pulmonary fibrosis is a progressive disease with only few treatment options available at the moment. Recently, the nucleoside uridine has been shown to exert anti-inflammatory effects in different animal models, e.g. in acute lung injury or bronchial asthma. METHOD: Therefore, we investigated the influence of uridine supplementation on inflammation and fibrosis in the classical bleomycin model. Male C57BL/6 mice received an intratracheal injection of bleomycin on day 0 and were treated intraperitoneally with uridine or vehicle. The degree of inflammation and fibrosis was assessed at different time points. RESULTS: Uridine administration resulted in attenuated inflammation, as demonstrated by reduced leukocytes and pro-inflammatory cytokines in the broncho-alveolar lavage (BAL) fluid. Furthermore, collagen deposition in the lung interstitium was also reduced by uridine supplementation. Similar results were obtained in a model in which animals received repeated intraperitoneal bleomycin injections. In addition uridine inhibited collagen and TGF-beta synthesis by primary lung fibroblasts, the release of pro-inflammatory cytokines by human lung epithelial cells, as well as the production of reactive oxygen species by human neutrophils. CONCLUSION: In summary, we were able to show that uridine has potent anti-inflammatory and anti fibrotic properties. As uridine supplementation has been shown to be well tolerated and safe in humans, this might be a new therapeutic approach for the treatment of fibrotic lung diseases. PMID- 26369418 TI - The complete mitochondrial genome of Cryptolestes turcicus (Grouvelle) (Coleoptera:Laemophloeidae). AB - We presented the complete mitogenome of Cryptolestes turcicus (GenBank accession number KT070712) in this study. The total length of mitochondrial DNA is 15 517 bp and contains 13 protein-coding genes, two ribosomal RNA genes, 22 transfer RNA genes, and a control region. The overall base composition of the genome is A (39.48%), T (37.38%), C (13.97%), and G (9.16%) with an A + T-rich hallmark. The start codon was ATN in all the mitochondrial protein-coding genes, such as ND2, COI, ATP6, ND5, ND4L and ND1 start with ATA, COII, ATP8, ND3, and ND6 genes employing ATT, while the rest using ATG as a start codon. The stop codon was mainly TAA or TAG in most of the mitochondrial protein-coding genes, wherever T(A) was found in COII, COIII, ND4, and ND4L genes. The A + T-rich region is located between 12S rRNA and tRNA(Ile) with a length of 857 bp. PMID- 26369419 TI - Online analysis of H2S and SO2 via advanced mid-infrared gas sensors. AB - Volatile sulfur compounds (VSCs) are among the most prevalent emitted pollutants in urban and rural atmospheres. Mainly because of the versatility of sulfur regarding its oxidation state (2- to 6+), VSCs are present in a wide variety of redox-environments, concentration levels, and molar ratios. Among the VSCs, hydrogen sulfide and sulfur dioxide are considered most relevant and have simultaneously been detected within naturally and anthropogenically caused emission events (e.g., volcano emissions, food production and industries, coal pyrolysis, and various biological activities). Next to their presence as pollutants, changes within their molar ratio may also indicate natural anomalies. Prior to analysis, H2S- and SO2-containing samples are usually preconcentrated via solid sorbents and are then detected by gas chromatographic techniques. However, such analytical strategies may be of limited selectivity, and the dimensions and operation modalities of the involved instruments prevent routine field usage. In this contribution, we therefore describe an innovative portable mid-infrared chemical sensor for simultaneously determining and quantifying gaseous H2S and SO2 via coupling a substrate-integrated hollow waveguides (iHWG) serving as a highly miniaturized mid-infrared photon conduit and gas cell with a custom-made preconcentration tube and an in-line UV-converter device. Both species were collected onto a solid sorbent within the preconcentrator and then released by thermal desorption into the UV-device. Hydrogen sulfide is detected by UV-assisted quantitative conversion of the rather weak IR-absorber H2S into SO2, which provides a significantly more pronounced and distinctively detectable rovibrational signature. Modulation of the UV-device system (i.e., UV-lamp on/off) enables discriminating between SO2 generated from H2S conversion and abundant SO2 signals. After optimization of the operational parameters, calibrations in the range of 0.75-10 ppmv with a limit of detection (LOD) at 77 ppbv for SO2 and 207 ppbv for H2S were established after 20 min of sampling time at 200 mL min(-1). Taking advantage of the device flexibility in terms of sampling time, flow-rate, and iHWG design facilitates tailoring the developed Preconcentrator-UV-device-iHWG device toward a wide variety of application scenarios ranging from environmental/atmospheric monitoring to industrial process monitoring and clinical diagnostics. PMID- 26369420 TI - Confinement, Desolvation, And Electrosorption Effects on the Diffusion of Ions in Nanoporous Carbon Electrodes. AB - Supercapacitors are electrochemical devices which store energy by ion adsorption on the surface of a porous carbon. They are characterized by high power delivery. The use of nanoporous carbon to increase their energy density should not hinder their fast charging. However, the mechanisms for ion transport inside electrified nanopores remain largely unknown. Here we show that the diffusion is characterized by a hierarchy of time scales arising from ion confinement, solvation, and electrosorption effects. By combining electrochemistry experiments with molecular dynamics simulations, we determine the in-pore conductivities and diffusion coefficients and their variations with the applied potential. We show that the diffusion of the ions is slower by 1 order of magnitude compared to the bulk electrolyte. The desolvation of the ions occurs on much faster time scales than electrosorption. PMID- 26369421 TI - Coexistence of Native-Like and Non-Native Cytochrome c on Anionic Liposomes with Different Cardiolipin Content. AB - We employed a combination of fluorescence, visible circular dichroism, and absorption spectroscopy to study the conformational changes of ferricytochrome c upon its binding to cardiolipin-containing small unilamellar vesicles. The measurements were performed as a function of the cardiolipin concentration, the cardiolipin content of the liposomes, and the NaCl concentration of the solvent. The data were analyzed with a novel model that combines a single binding step with a conformational equilibrium between native-like and non-native-like proteins bound to the membrane surface. The equilibrium between the two conformations, which themselves are comprised of structurally slightly different subconformations, shifts to the more non-native-like conformation with increasing cardiolipin concentration. For the binding isotherms described in this paper, we explicitly considered the enthalpic and entropic contributions of molecular crowding to protein binding at low lipid concentrations and high occupancy of the liposome surface. Increasing the CL content of liposomes increases the overall binding affinity but makes the conformational distribution much more susceptible to the influence of sodium and chloride ions, which shifts the equilibrium toward the more native-like state and directly inhibits binding, particularly to liposomes with 100% cardiolipin content. Spectroscopic evidence further suggests that a fraction of the non-native conformers adopts a pentacoordinated state similar to those obtained in class C peroxidases. On the basis of our results, we propose a hypothesis that describes the balance between facilitating and impeding forces controlling the peroxidase activity of cytochrome c in the inner membrane space of mitochondria. PMID- 26369422 TI - Development and validation of a stability indicating isocratic HPLC method for gemcitabine with application to drug release from poly lactic-co-glycolic acid nanoparticles and enzymatic degradation studies. AB - OBJECTIVES: Previously reported HPLC methods for gemcitabine determination are time-consuming with complicated mobile phases and gradient elution. Thus, a sensitive and stability-indicating isocratic HPLC method, which provides simple, fast and precise measurements, was developed. This method was applied to study the digestive enzymatic degradation of gemcitabine, for the first time, and the protection afforded following incorporation into poly lactic-co-glycolic acid (PLGA) nanoparticles. METHODS: An analytical HPLC method was developed with an optimized combination of operating conditions. Forced degradation and application of the method to in-vitro drug release studies were conducted. Finally, gemcitabine-loaded nanoparticles were exposed to the digestive enzymes pepsin, trypsin and alpha-chymotrypsin, and the resulting degradation evaluated. KEY FINDINGS: The analytical method was linear between 1 and 100 MUg/ml, with excellent accuracy of 99.91-101.77% and precision of 1.71 or lower, with a 0.014 MUg/ml limit of detection (LOD) and a 0.043 MUg/ml limit of quantification (LOQ). Following exposure of gemcitabine to stressors, the drug was relatively stable in strong acid (1 N HCl), base (1 N NaOH) and as an aqueous solution exposed to light over 7 days, with less than 10% degradation. However, gemcitabine was more susceptible to degradation at 70 degrees C and oxidative conditions (3% v/v H2 O2 ) with greater than 10% degradation noted after 7 days. In-vitro drug release studies demonstrated a sustained drug release profile from PLGA nanoparticles, which also improved the resistance of gemcitabine to enzymatic degradation. CONCLUSION: These results demonstrate the utility and effectiveness of this simple isocratic HPLC method in evaluating the overall performance of a gemcitabine-loaded formulation. PMID- 26369423 TI - Comparison of peritoneal dialysis catheter insertion techniques: Peritoneoscopic, radiological and laparoscopic : A single-centre study. AB - BACKGROUND: Our centre introduced peritoneoscopic insertion of peritoneal dialysis (PD) catheter by nephrologists as a new method in August 2009 for its potential benefits. AIM: The aim of this study was to compare perioperative complications and catheter survival of three techniques: peritoneoscopic, surgical and radiological techniques within a single dialysis centre. METHOD: This study used retrospective analysis of all PD catheter inserted from 1 August 2009 to 31 July 2013 within Counties Manukau DHB, Auckland, New Zealand. RESULTS: During the study period, 293 PD catheters were inserted, 84 (29%) peritoneoscopic (P), 140 (48%) surgical (S) and 69 (23%) radiological (R). Total duration of follow-up was 5848 catheter-months, with median follow-up of 17 months. There was no difference in perioperative exit-site infections and overall early infections. There was however increased overall perioperative complications in P compared with R (HR 2.08; P < 0.05), predominantly from catheter removal within 60 days. Although there was no difference observed in first catheter 1-year and overall survival between insertion techniques, there was poorer complication-free survival comparing P to S (HR 1.82, P = 0.001) but not to R. Analyses of the latter cohort of P confirmed improvement in catheter survival compared with an earlier cohort and to other insertion techniques. CONCLUSION: Peritoneoscopic PD catheter insertion is demonstrated to be a suitable alternative technique. As with any new procedure, 'learning curve' effects and development of operator expertise need to be taken into consideration. PMID- 26369424 TI - Bell's measure and implementing quantum Fourier transform with orbital angular momentum of classical light. AB - We perform Bell's measurement for the non-separable correlation between polarization and orbital angular momentum from the same classical vortex beam. The violation of Bell's inequality for such a non-separable classical correlation has been demonstrated experimentally. Based on the classical vortex beam and non quantum entanglement between the polarization and the orbital angular momentum, the Hadamard gates and conditional phase gates have been designed. Furthermore, a quantum Fourier transform has been implemented experimentally. PMID- 26369425 TI - Erratum to: Clustering of non-communicable diseases risk factors in Bangladeshi adults: an analysis of STEPS survey 2013. PMID- 26369426 TI - Epigenetics changes associated to environmental triggers in autoimmunity. AB - Autoimmune diseases (AIDs) are chronic conditions initiated by the loss of immunological tolerance to self-antigens and represent a heterogeneous group of disorders that affect specific target organs or multiple organs in different systems. While the pathogenesis of AID remains unclear, its aetiology is multifunctional and includes a combination of genetic, epigenetic, immunological and environmental factors. In AIDs, several epigenetic mechanisms are defective including DNA demethylation, abnormal chromatin positioning associated with autoantibody production and abnormalities in the expression of RNA interference (RNAi). It is known that environmental factors may interfere with DNA methylation and histone modifications, however, little is known about epigenetic changes derived of regulation of RNAi. An approach to the known environmental factors and the mechanisms that alter the epigenetic regulation in AIDs (with emphasis in systemic lupus erythematosus, the prototype of systemic AID) are showed in this review. PMID- 26369427 TI - Bioactive compounds of Eriocaulon sieboldianum blocking proliferation and inducing apoptosis of HepG2 cells might be involved in Aurora kinase inhibition. AB - Eriocaulon sieboldianum (Sieb. & Zucc. ex Steud.) is an edible and medicinal plant used in traditional Chinese medicine. Often in combination with other herbs, it is processed into healthcare beverages for expelling wind-heat, protecting eyes, and reducing blood lipids. Besides, its water decoction together with other herbs has been utilized to treat cancer in China. However, the active ingredients and the precise cellular mechanisms of E. sieboldianum remain to be elucidated. The Aurora kinase family plays critical roles in the regulation of cell division and has attracted great attention to the identification of small molecule Aurora kinase inhibitors for potential treatment of cancer. A molecular docking study was employed for docking of the most bioactive compounds. Hispidulin (HPDL) and quercetin-3-O-(6''-O-galloyl)-beta-D-galactopyranoside (QGGP) were singled out as potent inhibitors of Aurora kinase. Their inhibitory activity towards Aurora kinase was further confirmed by the obvious decrease in autophosphorylation of Aurora-A (Thr288) and Aurora-B (Thr232). Moreover, the induction of cell cycle arrest in HepG2 cells and the suppressed phosphorylation of histone H3 were also consistent with the inhibition of Aurora kinase. The data indicate that the E. sieboldianum extract and its two active compounds, HPDL and QGGP, could effectively induce apoptosis via p53, MAPKs and the mitochondrial apoptotic pathways. These findings could improve the understanding and enhance the development of drugs based on E. sieboldianum and raise its application value in anticancer therapy or prevention. In addition, our results indicated that Aurora kinase might be a novel target of HPDL and QGGP. PMID- 26369428 TI - Photoelectron diffraction from laser-aligned molecules with X-ray free-electron laser pulses. AB - We report on the measurement of deep inner-shell 2p X-ray photoelectron diffraction (XPD) patterns from laser-aligned I2 molecules using X-ray free electron laser (XFEL) pulses. The XPD patterns of the I2 molecules, aligned parallel to the polarization vector of the XFEL, were well matched with our theoretical calculations. Further, we propose a criterion for applying our molecular-structure-determination methodology to the experimental XPD data. In turn, we have demonstrated that this approach is a significant step toward the time-resolved imaging of molecular structures. PMID- 26369429 TI - Generation of macaques with sperm derived from juvenile monkey testicular xenografts. PMID- 26369430 TI - Murine somatic cell nuclear transfer using reprogrammed donor cells expressing male germ cell-specific genes. AB - In vivo-matured mouse oocytes were enucleated, and a single murine embryonic fibroblast (control or reprogrammed by introducing extracts from murine testis tissue, which showed expression of male germ cell-specific genes) was injected into the cytoplasm of the oocytes. The rate of blastocyst development and expression levels of Oct-4, Eomes and Cdx-2 were not significantly different in both experimental groups. However, the expression levels of Nanog, Sox9 and Glut 1 were significantly increased when reprogrammed cells were used as donor nuclei. Increased expression of Nanog can be supportive of complete reprogramming of somatic cell nuclear transfer murine embryos. The present study suggested that donor cells expressing male germ cell-specific genes can be reconstructed and can develop into embryos with normal high expression of developmentally essential genes. PMID- 26369431 TI - Effects of hypoxia and glucose-removal condition on muscle contraction of the smooth muscles of porcine urinary bladder. AB - To elucidate the dependence of aerobic energy metabolism and utilization of glucose in contraction of urinary bladder smooth muscle, we investigated the changes in the reduced pyridine nucleotide (PNred) fluorescence, representing glycolysis activity, and determined the phosphocreatine (PCr) and ATP contents of the porcine urinary bladder during contractions induced by high K(+) or carbachol (CCh) and with and without hypoxia (achieved by bubbling N2 instead of O2) or in a glucose-free condition. Hyperosmotic addition of 65 mM KCl (H-65K(+)) and 1 uM CCh induced a phasic contraction followed by a tonic contraction. A glucose-free physiological salt solution (PSS) did not change the subsequent contractile responses to H-65K(+) and CCh. However, hypoxia significantly attenuated H-65K(+) and CCh-induced contraction. H-65K(+) and CCh induced a sustained increase in PNred fluorescence, representing glycolysis activity. Hypoxia enhanced H-65K(+)- and CCh-induced increases in PNred fluorescence, whereas glucose-free PSS decreased these increases, significantly. In the presence of H-65K(+), hypoxia decreased the PCr and ATP contents; however, the glucose-free PSS did not change the PCr contents. In conclusion, we demonstrated that high K(+)- and CCh-induced contractions depend on aerobic metabolism and that an endogenous substrate may be utilized to maintain muscle contraction in a glucose-free PSS in the porcine urinary bladder. PMID- 26369432 TI - In vitro susceptibility of Brachyspira hyodysenteriae to organic acids and essential oil components. AB - The antibacterial potential of organic acids and essential oil components against Brachyspira hyodysenteriae, the causative pathogen of swine dysentery, was evaluated. Minimum inhibitory concentrations (MIC) of 15 compounds were determined at pH 7.2 and pH 6.0, using a broth microdilution assay. In addition, possible synergism was determined. MIC values for the three tested strains were similar. For organic acids, MIC values at pH 6.0 were lower than at pH 7.2. B. hyodysenteriae was most sensitive to cinnamaldehyde and lauric acid, with MIC values <1.5 mM. Most antibacterial effects of binary combinations were additive, however, for thymol and carvacrol, synergism could be observed. In vitro results demonstrate the antibacterial action of certain essential oil components and organic acids against B. hyodysenteriae. PMID- 26369433 TI - Hurricane Sandy: Impact on Emergency Department and Hospital Utilization by Older Adults in Lower Manhattan, New York (USA). AB - BACKGROUND: On October 29th, 2012, Hurricane Sandy caused a storm surge interrupting electricity with disruption to Manhattan's (New York, USA) health care infrastructure. Beth Israel Medical Center (BIMC) was the only fully functioning major hospital in lower Manhattan during and after Hurricane Sandy. The impact on emergency department (ED) and hospital use by geriatric patients in lower Manhattan was studied. METHODS: The trends of ED visits and hospitalizations in the immediate post-Sandy phase (IPS) during the actual blackout (October 29 through November 4, 2012), and the extended post-Sandy phase (EPS), when neighboring hospitals were still incapacitated (November 5, 2012 through February 10, 2013), were analyzed with baseline. The analysis was broken down by age groups (18-64, 65-79, and 80+ years old) and included the reasons for ED visits and admissions. RESULTS: During the IPS, there was a significant increase in geriatric visits (from 11% to 16.5% in the 65-79 age group, and from 6.5% to 13% in the 80+ age group) as well as in hospitalizations (from 22.7% to 25.2% in the 65-79 age group, and from 17.6% to 33.8% in the 80+ age group). However, these proportions returned to baseline during the EPS. The proportions of the categories "dialysis," "respiratory device," "social," and "syncope" in geriatric patients in ED visits were significantly higher than younger patients. The increases of the categories "medication," "dialysis," "respiratory device," and "social" represented two-thirds of absolute increase in both ED visits and admissions for the 65-79 age group, and half of the absolute increase in ED visits for the 80+ age group. The categories "social" and "respiratory device" peaked one day after the disaster, "dialysis" peaked two days after, and "medication" peaked three days after in ED visit analysis. CONCLUSIONS: There was a disproportionate increase in ED visits and hospitalizations in the geriatric population compared with the younger population during the IPS. The primary factor of the disproportionate impact on the geriatric population appears to be from indirect effects of the hurricane, mainly due to the subsequent power outages, such as "dialysis," "respiratory device," and "social." Further investigation by chart review may provide more insights to better aid with future disaster preparedness. PMID- 26369434 TI - Environmental factors affecting seasonality of ambulance emergency service visits for exacerbations of asthma and COPD. AB - OBJECTIVE: The aim of this study was to assess the association of severe exacerbations of asthma and Chronic Obstructive Pulmonary Disease (COPD) requiring ambulance emergency service (AES) visits with meteorological parameters and influenza outbreaks. METHODS: The records of patients calling the AES in 2007 and 2008 in the urban area of Lodz due to dyspnea were analyzed. Information on 25 daily reported meteorological parameters was obtained from the local meteorological service and data on influenza outbreaks obtained from the national surveillance service. RESULTS: During the winter months, a significantly higher mean daily number of AES visits for both COPD and asthma were noticed when compared to the summer. Interestingly, the number of daily AES visits correlated with several weather parameters, and the multiple regression analysis confirmed a negative correlation with minimum temperature, mean temperature and the dew point for both diseases (R = 0.526; p < 0.01; R = 0.577; p < 0.01 and R = 0.589; p < 0.01). Furthermore, the increased number of AES visits also correlated with a new number of cases of influenza infections as reported by local influenza surveillance system (rs = 77.6%; p < 0.001 and rs = 80.8%; p < 0.001 for asthma and COPD, respectively). CONCLUSION: Seasonality of AES visits for asthma and COPD are similar and seems to be related to specific weather conditions and to influenza outbreaks. PMID- 26369435 TI - A hybridisation-dependent membrane-insertable amphiphilic DNA. AB - We synthesised a novel membrane-insertable amphiphilic DNA. The amphiphilic DNA had a nine-nucleotide hydrophobic region at one end consisting of octyl phosphotriester linkages. The amphiphilic DNA bound to the lipid membrane by inserting the hydrophobic region; this process was facilitated by the presence of the complementary DNA strand. PMID- 26369437 TI - Engineering the central biosynthetic and secondary metabolic pathways of Pseudomonas aeruginosa strain PA1201 to improve phenazine-1-carboxylic acid production. AB - The secondary metabolite phenazine-1-carboxylic acid (PCA) is an important component of the newly registered biopesticide Shenqinmycin. We used a combined method involving gene, promoter, and protein engineering to modify the central biosynthetic and secondary metabolic pathways in the PCA-producing Pseudomonas aeruginosa strain PA1201. The PCA yield of the resulting strain PA-IV was increased 54.6-fold via the following strategies: (1) blocking PCA conversion and enhancing PCA efflux pumping; (2) increasing metabolic flux towards the PCA biosynthetic pathway through the over-production of two DAHP synthases and blocking the synthesis of 21 secondary metabolites; (3) increasing the PCA precursor supply through the engineering of five chorismate-utilizing enzymes; (4) engineering the promoters of two PCA biosynthetic gene clusters. Strain PA-IV produced 9882 mg/L PCA in fed-batch fermentation, which is twice as much as that produced by the current industrial strain. Strain PA-IV was also genetically stable and comparable to Escherichia coli in cytotoxicity. PMID- 26369438 TI - Elimination of metabolic pathways to all traditional fermentation products increases ethanol yields in Clostridium thermocellum. AB - Clostridium thermocellum has the natural ability to convert cellulose to ethanol, making it a promising candidate for consolidated bioprocessing (CBP) of cellulosic biomass to biofuels. To further improve its CBP capabilities, a mutant strain of C. thermocellum was constructed (strain AG553; C. thermocellum Deltahpt DeltahydG Deltaldh Deltapfl Deltapta-ack) to increase flux to ethanol by removing side product formation. Strain AG553 showed a two- to threefold increase in ethanol yield relative to the wild type on all substrates tested. On defined medium, strain AG553 exceeded 70% of theoretical ethanol yield on lower loadings of the model crystalline cellulose Avicel, effectively eliminating formate, acetate, and lactate production and reducing H2 production by fivefold. On 5 g/L Avicel, strain AG553 reached an ethanol yield of 63.5% of the theoretical maximum compared with 19.9% by the wild type, and it showed similar yields on pretreated switchgrass and poplar. The elimination of organic acid production suggested that the strain might be capable of growth under higher substrate loadings in the absence of pH control. Final ethanol titer peaked at 73.4mM in mutant AG553 on 20 g/L Avicel, at which point the pH decreased to a level that does not allow growth of C. thermocellum, likely due to CO2 accumulation. In comparison, the maximum titer of wild type C. thermocellum was 14.1mM ethanol on 10 g/L Avicel. With the elimination of the metabolic pathways to all traditional fermentation products other than ethanol, AG553 is the best ethanol-yielding CBP strain to date and will serve as a platform strain for further metabolic engineering for the bioconversion of lignocellulosic biomass. PMID- 26369436 TI - A draft genome sequence of an invasive mosquito: an Italian Aedes albopictus. AB - The draft genome sequence of Italian specimens of the Asian tiger mosquito Aedes (Stegomyia) albopictus (Diptera: Culicidae) was determined using a standard NGS (next generation sequencing) approach. The size of the assembled genome is comparable to that of Aedes aegypti; the two mosquitoes are also similar as far as the high content of repetitive DNA is concerned, most of which is made up of transposable elements. Although, based on BUSCO (Benchmarking Universal Single Copy Orthologues) analysis, the genome assembly reported here contains more than 99% of protein-coding genes, several of those are expected to be represented in the assembly in a fragmented state. We also present here the annotation of several families of genes (tRNA genes, miRNA genes, the sialome, genes involved in chromatin condensation, sex determination genes, odorant binding proteins and odorant receptors). These analyses confirm that the assembly can be used for the study of the biology of this invasive vector of disease. PMID- 26369440 TI - From the Editor. PMID- 26369439 TI - Engineering Methylobacterium extorquens for de novo synthesis of the sesquiterpenoid alpha-humulene from methanol. AB - Over the last 10 to 15 years, metabolic engineering of microbes has become a versatile tool for high-level de novo synthesis of terpenoids, with the sesquiterpenoids armopha-1,4-diene, farnesene and artemisinic acid as prime examples. However, almost all cell factory approaches towards terpenoids to date have been based on sugar as the raw material, which is mainly used as a food resource and subject to high price volatilities. In this study we present de novo synthesis of the sesquiterpenoid alpha-humulene from the abundantly available non food carbon source methanol by metabolically engineered Methylobacterium extorquens AM1. Expression of alpha-humulene synthase from Zingiber zerumbet in combination with farnesyl pyrophosphate (FPP) synthase from Saccharomyces cerevisiae led to concentrations of up to 18 mg/L alpha-humulene. Introduction of a prokaryotic mevalonate pathway from Myxococcus xanthus in combination with ribosome binding site optimization of alpha-humulene and FPP synthases increased product concentration 3-fold. This value was additionally raised by 30% using a carotenoid synthesis deficient mutant strain. Final product concentrations of up to 1.65 g/L were obtained in methanol limited fed-batch cultivations, which is the highest titer of de novo synthesized alpha-humulene reported to date. This study demonstrates the potential of M. extorquens as a future platform strain for the production of high-value terpenoids from the alternative carbon source methanol. PMID- 26369441 TI - Efficacy of folic acid in primary prevention of stroke among patients with hypertension in China. PMID- 26369442 TI - Partnering with patients using social media to develop a hypertension management instrument. AB - Hypertension is a lifelong condition; thus, long-term adherence to lifestyle modification, self-monitoring, and medication regimens remains a challenge for patients. The aim of this study was to develop a patient-reported hypertension instrument that measured attitudes, lifestyle behaviors, adherence, and barriers to hypertension management using patient-reported outcome data. The study was conducted using the Open Research Exchange software platform created by PatientsLikeMe. A total of 360 participants completed the psychometric phase of the study; incomplete responses were obtained from 147 patients, and 150 patients opted out. Principal component analysis with orthogonal (varimax) rotation was executed on a data set with all completed responses (N = 249) and applied to 43 items. Based on the review of the factor solution, eigenvalues, and item loadings, 16 items were eliminated and model with 29 items was tested. The process was repeated two more times until final model with 14 items was established. In interpreting the rotated factor pattern, an item was said to load on any given component if the factor loading was >=0.40 for that component and was <0.40 for the other. In addition to the newly generated instrument, demographic and self-reported clinical characteristics of the study participants such as the type of prescribed hypertension medications, frequency of blood pressure monitoring, and comorbid conditions were examined. The Open Research Exchange platform allowed for ongoing input from patients through each stage of the 14-item instrument development. PMID- 26369443 TI - Analysis of arterial wall remodeling in hypertension based on lamellar modeling. AB - Arterial wall remodels its geometry and mechanical properties in response to hypertension to maintain functionality. The elevated pressure is sensed through cellular mechanotransduction pathways, and extra extracellular matrix is synthesized, leading to thickening and stiffening. The present study enquires the response of aortic lamellar structure to hypertensive blood pressure regarding unchanged circumferential stress "profile" across the media as remodeling criterion. We tested the hypothesis that alterations in the thickness of structural layers contributes to maintain stress profile with least deviation from normotensive conditions. To test this notion, finite element analysis was recruited to evaluate stress profile, considering wall residual stress, and lamellar structure was adjusted through an optimization algorithm. Our results indicated 47% increased thickness of the aortic media that originates from nonhomogenous thickening of the microstructural units. The thickening and stiffening responses of the wall tissue were coupled, and the optimized pattern of hypertension-induced remodeling was established. PMID- 26369444 TI - Post-dispersal seed removal by ground-feeding rodents in tropical peatlands, Central Kalimantan, Indonesia. AB - Forested tropical peatlands in Southeast Asia are being rapidly converted to agriculture or degraded into non-forest vegetation. Although large areas have been abandoned, there is little evidence for subsequent forest recovery. As part of a study of forest degradation and recovery, we used seed removal experiments and rodent surveys to investigate the potential role of post-dispersal seed predation in limiting the regeneration of woody plants. Two 14-day seed removal trials were done in deforested and forested peatland habitat in Central Kalimantan, Indonesia. Seeds of Nephelium lappaceum, Syzygium muelleri, Artocarpus heterophyllus (all animal-dispersed) and Combretocarpus rotundatus (wind-dispersed) were tested. Significantly more seeds (82.8%) were removed in forest than non-forest (38.1%) and Combretocarpus had the lowest removal in both habitats. Most handled seeds were eaten in situ and little caching was observed. Six species of rodents were captured in forest and five in non-forest. The most trapped taxa were three Maxomys spp. in forest (85.5% of individuals) and Rattus tiomanicus in non-forest (74.8%). Camera traps confirmed that rodents were responsible for seed removal. Seed predation in deforested areas, which have a much lower seed rain than forest, may contribute to the low density and diversity of regenerating forest. PMID- 26369445 TI - Limb movement frequency is a significant modulator of the ventilatory response during submaximal cycling exercise in humans. AB - Human experimentation investigating the contribution of limb movement frequency in determining the fast exercise drive to breathe has produced controversial findings. To evaluate the role of limb movement frequency in determining the fast exercise drive to breathe, endurance runners and recreationally-active controls performed two sinusoidal exercise protocols on a cycle ergometer. One protocol was performed at constant workload with sinusoidal pedaling cadence, and a second with sinusoidal workload at constant cadence. Metabolic rate (VO2) increases and means were matched between these two experiments. The ventilatory response was significantly faster when limb movement speed was varied, compared to when pedal loading was varied (18.49 +/- 15.6s vs. 50.5 +/- 14.5s, p<0.05). Ventilation response amplitudes were significantly higher during pedal cadence variation versus pedal loading variation (3.99 +/- 0.25 vs. 2.58 +/- 0.17 L/min, p<0.05). Similar findings were obtained for endurance athletes, with significantly attenuated ventilation responses to exercise versus control subjects. We conclude that fast changes in limb movement frequency are a potent stimulus for ventilation at submaximal workloads, and that this response is susceptible to attenuation through training. PMID- 26369446 TI - Association of the forced oscillation technique with negative expiratory pressure in COPD. AB - Expiratory flow limitation (EFL) during tidal breathing is common in patients with severe COPD, and a major determinant of dynamic hyperinflation and exercise limitation. The negative expiratory pressure (NEP) technique has been the gold standard to detect EFL, while the forced oscillation technique (FOT) has also been reported to detect it. However, the association of FOT with NEP is not fully understood. We assessed whether broadband frequency FOT would predict the presence of EFL measured by NEP. FOT, NEP, and spirometry were performed in 51 patients with COPD. The extent of emphysema was measured by high-resolution computed tomography and scored. Fifteen patients were classified into the EFL positive group and 36 into the EFL-negative group. In multivariate logistic regression analysis, EFL was independently predicted by emphysema score, forced vital capacity, and whole-breath respiratory system reactance at 5Hz (X5). The receiver operator characteristic curve analysis revealed that inspiratory X5 best predicted EFL-positivity. X5-related forced oscillatory parameters are useful for detecting EFL in the management of COPD. PMID- 26369447 TI - A global assessment of dementia, now and in the future. PMID- 26369448 TI - Paolo Macchiarini is not guilty of scientific misconduct. PMID- 26369449 TI - Diabetes: an ounce of prevention is worth a pound of cure. PMID- 26369450 TI - A global perspective on dementia care: a Lancet Commission. PMID- 26369451 TI - Type 2 diabetes: multimodal treatment of a complex disease. PMID- 26369452 TI - Oral corticosteroids for multiple sclerosis relapse. PMID- 26369455 TI - Anti-abortion groups target funding of Planned Parenthood. PMID- 26369456 TI - Budget cuts threaten AIDS and tuberculosis control in India. PMID- 26369457 TI - Measles outbreak in DR Congo an "epidemic emergency". PMID- 26369458 TI - Profile: Joslin Diabetes Center, Boston, MA, USA. PMID- 26369459 TI - Lancet. PMID- 26369461 TI - George King: research leader at the Joslin Diabetes Center. PMID- 26369462 TI - Dora in the 21st century. PMID- 26369463 TI - Jules Hirsch. PMID- 26369464 TI - 24/7 consultant presence in a UK NHS tertiary maternity unit. PMID- 26369465 TI - Academic primary care and the general practice workforce. PMID- 26369466 TI - Corticosteroid therapy for pneumonia. PMID- 26369467 TI - Causes of child death estimates: making use of the InterVA model. PMID- 26369468 TI - Corticosteroid therapy for pneumonia. PMID- 26369469 TI - Corticosteroid therapy for pneumonia. PMID- 26369470 TI - Corticosteroid therapy for pneumonia. PMID- 26369471 TI - Corticosteroid therapy for pneumonia. PMID- 26369472 TI - Corticosteroid therapy for pneumonia - Author's reply. PMID- 26369473 TI - Bariatric-metabolic surgery versus conventional medical treatment in obese patients with type 2 diabetes: 5 year follow-up of an open-label, single-centre, randomised controlled trial. AB - BACKGROUND: Randomised controlled trials have shown that bariatric surgery is more effective than conventional treatment for the short-term control of type-2 diabetes. However, published studies are characterised by a relatively short follow-up. We aimed to assess 5 year outcomes from our randomised trial designed to compare surgery with conventional medical treatment for the treatment of type 2 diabetes in obese patients. METHODS: We did our open-label, randomised controlled trial at one diabetes centre in Italy. Patients aged 30-60 years with a body-mass index of 35 kg/m(2) or more and a history of type 2 diabetes lasting at least 5 years were randomly assigned (1:1:1), via a computer-generated randomisation procedure, to receive either medical treatment or surgery by Roux en-Y gastric bypass or biliopancreatic diversion. Participants were aware of treatment allocation before the operation and study investigators were aware from the point of randomisation. The primary endpoint was the rate of diabetes remission at 2 years, defined as a glycated haemaglobin A1c (HbA1c) concentration of 6.5% or less (<=47.5 mmol/mol) and a fasting glucose concentration of 5.6 mmol/L or less without active pharmacological treatment for 1 year. Here we analyse glycaemic and metabolic control, cardiovascular risk, medication use, quality of life, and long-term complications 5 years after randomisation. Analysis was by intention to treat for the primary endpoint and by per protocol for the 5 year follow-up. This study is registered with ClinicalTrials.gov, number NCT00888836. FINDINGS: Between April 27, 2009, and Oct 31, 2009, we randomly assigned 60 patients to receive either medical treatment (n=20) or surgery by gastric bypass (n=20) or biliopancreatic diversion (n=20); 53 (88%) patients completed 5 years' follow-up. Overall, 19 (50%) of the 38 surgical patients (seven [37%] of 19 in the gastric bypass group and 12 [63%] of 19 in the bilipancreatic diversion group) maintained diabetes remission at 5 years, compared with none of the 15 medically treated patients (p=0.0007). We recorded relapse of hyperglycaemia in eight (53%) of the 15 patients who achieved 2 year remission in the gastric bypass group and seven (37%) of the 19 patients who achieved 2 year remission in the biliopancreatic diversion group. Eight (42%) patients who underwent gastric bypass and 13 (68%) patients who underwent biliopancreatic diversion had an HbA1c concentration of 6.5% or less (<=47.5 mmol/mol) with or without medication, compared with four (27%) medically treated patients (p=0.0457). Surgical patients lost more weight than medically treated patients, but weight changes did not predict diabetes remission or relapse after surgery. Both surgical procedures were associated with significantly lower plasma lipids, cardiovascular risk, and medication use. Five major complications of diabetes (including one fatal myocardial infarction) arose in four (27%) patients in the medical group compared with only one complication in the gastric bypass group and no complications in the biliopancreatic diversion group. No late complications or deaths occurred in the surgery groups. Nutritional side-effects were noted mainly after biliopancreatic diversion. INTERPRETATION: Surgery is more effective than medical treatment for the long-term control of obese patients with type 2 diabetes and should be considered in the treatment algorithm of this disease. However, continued monitoring of glycaemic control is warranted because of potential relapse of hyperglycaemia. FUNDING: Catholic University of Rome. PMID- 26369474 TI - Adult-onset renal thrombotic microangiopathy and pulmonary arterial hypertension in cobalamin C deficiency. PMID- 26369475 TI - Cobalamin C deficiency-associated thrombotic microangiopathy: uncommon or unrecognised? PMID- 26369476 TI - Structural investigation of Na3NpO4 and Na3PuO4 using X-ray diffraction and (237)Np Mossbauer spectroscopy. AB - alpha-Na3NpO4 and alpha-Na3PuO4 exhibit an orthorhombic structure (Z = 8), in space group Fmmm, with lattice parameters a = 13.352(2) A, b = 9.629(2) A, and c = 6.673(2) A for the neptunium compound, and a = 13.302(2) A, b = 9.634(2) A, and c = 6.651(2) A for the plutonium analogue. The corresponding structure has been solved ab initio as no structural analogue could be found in the literature. The pentavalent state of neptunium has moreover been confirmed by (237)Np Mossbauer spectroscopy, and the local structural properties inferred from the X-ray Rietveld refinement have been related to the fitted quadrupole coupling constant and asymmetry parameters. The existence of a low temperature metastable m phase of Na3NpO4 and Na3PuO4, of the NaCl type, has also been suggested. PMID- 26369478 TI - An update on myasthenia gravis, challenging disease for the dental profession. AB - Myasthenia gravis is an autoimmune neuromuscular disorder characterized by fluctuating weakness and skeletal muscle fatigue. Clinical signs and symptoms may vary considerably according to the age at presentation, patterns of autoantibodies and associated thymic abnormalities, so that therapeutic options are highly individualized. Facial and oropharyngeal muscle weakness is common at disease onset, and therefore dentists are often the first health professionals to encounter these patients. Myasthenic patients require special consideration and advice in order to ensure optimal and safe dental treatment. Oral manifestations, treatment timing and modality, the choice and effects of drugs and medications, and prevention of myasthenic crisis are all important aspects with which dentists and oral health care providers should be thoroughly acquainted. PMID- 26369479 TI - Translational approach utilizing COX-2, p53, and MDM2 expressions in malignant transformation of oral submucous fibrosis. AB - About 20% of the world's population uses some form of betel nut, which suggests that the incidence of oral submucous fibrosis (OSF) is higher than current estimates. OSF has the potential to undergo malignant transformation; thus, there is a need to identify relevant markers to assess its aggressiveness. We evaluated changes in COX-2, p53, and MDM2 expressions in progressive OSF. Expressions of COX-2, p53, and MDM2 increased with OSF progression. There was a strong association between COX-2 overexpression and recurrence of oral squamous cell carcinoma (P < 0.001) and a positive relation between increased MDM2 expression and failure of radiotherapy (P = 0.007). These findings suggest that COX-2 is an important marker of disease progression and that MDM2 expression is useful for treatment planning. PMID- 26369477 TI - Efficacy study of two novel hyaluronic acid-based formulations for viscosupplementation therapy in an early osteoarthrosic rabbit model. AB - Viscosupplementation (VS) is a therapy for osteoarthrosis (OA) consisting of repetitive intra-articular injections of hyaluronic acid (HA). It is known to be clinically effective in relieving pain and increasing joint mobility by restoring joint homeostasis. In this study, the effects of two novel HA-based VS hydrogel formulations were assessed and challenged against a pure HA commercial formulation for the first time and this in a rabbit model of early OA induced by anterior cruciate ligament transection (ACLT). The first formulation tested was a hybrid hydrogel composed of HA and reacetylated chitosan, a biopolymer considered to be chondroprotective, assembled thanks to an ionic shielding. The second formulation consisted of a novel HA polymer grafted with antioxidant molecules (HA-4AR) aiming at decreasing OA oxidative stress and increasing HA retention time in the articulation. ACLT was performed on rabbits in order to cause structural changes comparable to traumatic osteoarthrosis. The protective effects of the different formulations were observed on the early phase of the pathology in a full randomized and blinded manner. The cartilage, synovial membrane, and subchondral bone were evaluated by complementary investigation techniques such as gross morphological scoring, scanning electron microscopy, histological scoring, and micro-computed tomography were used. In this study, ACLT was proven to successfully reproduce early OA articular characteristics found in humans. HA and HA-4AR hydrogels were found to be moderately protective for cartilage as highlighted by MUCT. The HA-4AR was the only formulation able to decrease synovial membrane hypertrophy occurring in OA. Finally, the hybrid HA reacetylated chitosan hydrogel surprisingly led to increased subchondral bone remodeling and cartilage defect formation. This study shows significant effects of two innovative HA modification strategies in an OA rabbit model, which warrant further studies toward more effective viscosupplementation formulations. PMID- 26369480 TI - Micro-computed tomographic analysis of progression of artificial enamel lesions in primary and permanent teeth after resin infiltration. AB - We investigated inhibition of lesion progression in artificial enamel lesions. Lesions were created on primary and permanent anterior teeth (n = 10 each) and were divided randomly into two groups with two windows: Group 1 (window A: resin infiltration; window B: negative control) and Group 2 (window A: resin infiltration + fluoride varnish; window B: fluoride varnish). After pH cycling, micro-computed tomography was used to analyze progression of lesion depth and changes in mineral density. Resin infiltration and resin infiltration + fluoride varnish significantly inhibited progression of lesion depth in primary teeth (P < 0.05). Inhibition of lesion depth progression in permanent teeth was significantly greater after treatment with resin infiltration + fluoride varnish than in the negative control (P < 0.05). Change in mineral density was smaller in the resin infiltration and resin infiltration + fluoride varnish groups; however, the difference was not significant for either group (P > 0.05). Resin infiltration is a promising method of inhibiting progression of caries lesions. PMID- 26369481 TI - The effect of blood contamination on dislocation resistance of different endodontic reparative materials. AB - This study evaluated the retention characteristics of ProRoot mineral trioxide aggregate (MTA), RetroMTA, Supra MTA, and Biodentine biomaterials used to repair furcation perforations contaminated with blood. Furcal perforations measuring 1.3 mm in diameter and 2 mm in height were created in 96 mandibular first molar teeth, which were then randomly divided into the following two groups (n = 48): contaminated (+) or non-contaminated (-) with blood. The groups were subdivided into four groups (n = 12) according to the material used (ProRoot MTA, RetroMTA, Supra MTA, and Biodentine) to seal the perforations. The samples were allowed to set for 14 days and were then subjected to push-out testing. The results were analyzed using ANOVA, and the failure modes were examined using a surgical microscope. ProRoot MTA (+/-) and RetroMTA (+/-) exhibited superior bond strength values; in addition, there were no significant differences among these groups (P > 0.05). Biodentine (+) showed intermediate values that were sometimes statistically similar to the ProRoot MTA (+/-) and RetroMTA (+/-) groups (P > 0.05) and, at other times, the Biodentine (-) and Supra MTA (+/-) groups (P > 0.05). The lowest bond strength values were shown by the Biodentine (-) and Supra MTA groups (P > 0.05). "Adhesive failure mode" was the most frequently observed type for all tested materials. Blood contamination did not affect the dislocation resistance of materials. PMID- 26369482 TI - Prevalence of dental trauma and mouthguard awareness among weekend warrior soccer players. AB - Traumatic dental and facial injuries are frequent in sports and often cause esthetic, functional, psychological, and economic problems. The term "weekend warrior" is used to describe people who participate in physically demanding activities only on the weekend, or part-time. In this prospective cohort study, we examined the prevalence of dental trauma and knowledge of traumatic dental injuries among weekend warriors in Ankara, Turkey. A detailed questionnaire on mouthguard awareness and knowledge and experience of dental trauma was distributed to 1,007 weekend warrior athletes participating in a soccer tournament. The results showed that 9.8% of participants had experienced orofacial trauma, 21.7% were aware of mouthguards, 2.9% reported using mouthguards, 15.4% were aware of the field of sports dentistry, and 19.6% were aware of emergency treatment for dental trauma. Participation in sports, especially contact sports, greatly increases the risk of dental injury. The present results show that knowledge of traumatic orofacial and dental injuries is limited among weekend warriors. Public health authorities should develop relevant educational programs, including broad dissemination of information on the risks of traumatic dental injuries and methods for protection against such injuries. PMID- 26369483 TI - Hounsfield unit comparison of grafted versus non-grafted extraction sockets. AB - Volumetric changes of the alveolar ridge after socket preservation with various techniques have been investigated frequently. However, changes in bone density and quality of bone within the extraction sockets have seldom been studied. The purpose of this study was to evaluate the bone quality of grafted versus non grafted socket sites prior to dental implant placement using Hounsfield unit (HU) values derived from cone-beam computed tomography (CBCT) imaging. The data was collected from 39 healed extraction sites reviewed over a one-year period. Subjects eligible for the study had a bone replacement graft and barrier membrane. Both study and control groups had CBCT scans performed immediately after extraction and four to five months after extraction for planning implant placement. HU values were measured from the CBCT scans and compared between groups. Intragroup variability was assessed utilizing standard deviation and standard error of the mean. Intergroup differences were evaluated using unpaired t-test. A generalized lack of significant difference in bone quality was observed between groups with the only statistically significant difference observed in the posterior maxilla. Future radiographic and histologic assessments of bone quality after socket preservation are required to determine the 'ideal' approach to preserve an extraction socket prior to implant placement. PMID- 26369484 TI - Periodontal and glycemic effects of nonsurgical periodontal therapy in patients with type 2 diabetes stratified by baseline HbA1c. AB - We evaluated the effects of nonsurgical periodontal therapy in 100 patients with type 2 diabetes and chronic periodontitis. The participants were classified as having good (n = 48) or poor (n = 52) glycemic control and were further randomly allocated to receive either scaling and root planning treatment group or no treatment (n = 50 each). The effect of nonsurgical periodontal therapy was compared among diabetic patients with good glycemic control, those with poor glycemic control, and 25 nondiabetic individuals. Periodontal and metabolic status was recorded at baseline, 3 months, and 6 months. In patients receiving treatment, periodontal parameters significantly improved and HbA1c decreased by 10.8%. Improvements in gingival index and bleeding on probing were greater in the nondiabetic participants and the treated patients with good glycemic control than in the treated patients with poor glycemic control (P < 0.05). Regression analysis showed that improvement in periodontal status was independently associated with glycemic improvement. Nonsurgical periodontal therapy improved glycemic control and periodontal health in patients with type 2 diabetes. However, patients with poor baseline glycemic control had less clinical improvement than did those without diabetes and those with good glycemic control. PMID- 26369485 TI - Inhibitory effect of gels loaded with a low concentration of antibiotics against biofilm formation by Enterococcus faecalis and Porphyromonas gingivalis. AB - We explored longitudinally the inhibitory effect of gels loaded with 1 mg/mL modified triple antibiotic paste (MTAP) or double antibiotic paste (DAP) against biofilm formation by Enterococcus faecalis and Porphyromonas gingivalis. Methylcellulose-based antibiotic gels of MTAP (ciprofloxacin, metronidazole and clindamycin) and DAP (ciprofloxacin and metronidazole) were prepared at a concentration of 1 mg/mL. Individually cultured E. faecalis and P. gingivalis bacterial suspensions were treated with MTAP, DAP, or placebo (vehicle only) gels at different dilutions and allowed to grow in 96-well microtiter plates. Untreated bacterial suspensions served as a negative control. Crystal violet assays were used to evaluate biofilm formation after 48 h. The ability of the gels to inhibit biofilm formation was determined immediately, and at 1 month and 3 months after the gels had been prepared. Data were analyzed using a mixed-model ANOVA. The MTAP and DAP gels significantly reduced biofilm formation by both bacterial species at all time points, regardless of the tested dilution. No significant differences in biofilm-inhibitory effects between MTAP and DAP gels were observed at the majority of the tested dilutions through various time points. Gels loaded with 1 mg/mL MTAP and DAP demonstrated a significant antibiofilm effect against E.faecalis and P. gingivalis. PMID- 26369486 TI - Suture materials affect peri-implant bone healing and implant osseointegration. AB - The aim of this study was to evaluate the effects of the remnants of two suture materials on osseointegration of titanium implants in a rabbit tibial model. Calibrated defects were prepared in the tibia of five Chinchilla rabbits. Filaments of nonresorbable (NR) nylon or resorbable (R) chitosan were placed at the bone to implant interface, whereas control sites had no suture material. After a healing period of 4 weeks, a pull-out test procedure was performed followed by enzymatic analyses of the wound fluid and relative quantification of mRNA levels for bone-related and cytokine markers from the peri-implant bone. A trend toward a reduced pull-out force was observed in the NR group (NR: 23.0 +/- 12.8 N; R: 33.9 +/- 11.3 N; control: 33.6 +/- 24.0 N). Similarly, the bone resorption marker vacuolar type H+-ATPase was increased in the NR group compared with that in the control group (P = 0.041). The R group showed trends for lower alkaline phosphatase activity and osteocalcin expression and higher total protein content and RNA compared with the control group. In this submerged healing model, peri-implant bone healing was marginally affected by the two suture materials tested. However, there was a tendency toward better osseointegration and lower expression of bone resorption markers in the R group compared with the control group. PMID- 26369487 TI - UVA-activated riboflavin improves the strength of human dentin. AB - The aim of this study was to evaluate the effects of UVA-activated riboflavin (UVA-RF) on the mechanical properties of non-demineralized human dentin. Dentin specimens obtained from 20 teeth were randomly divided into the following four groups: group 1 (control): no treatment, group 2 (low UVA-RF): specimens were exposed to UVA-RF for 10 min, group 3 (medium UVA-RF): specimens were exposed to UVA-RF for 30 min, and group 4 (high UVA-RF): specimens were exposed to UVA-RF for 60 min. Three-point flexural test and Raman spectroscopic analyses were performed. The mean flexural strengths (MPa) were 129.96, 128.96, 144.21, and 147.54, and the mean elastic modulus (GPa) were 8.59, 8.38, 10.21, and 9.87 for groups 1 to 4, respectively. Raman spectra showed chemical modifications of dental collagen under medium and high UVA-RF treatment. We conclude that medium and high UVA-RF increases the strength of non-demineralized human dentin by collagen crosslinking. PMID- 26369488 TI - Assessment of quality and interpretation of panoramic radiographs obtained in the Lao People's Democratic Republic as part of a teleradiology collaboration with Japan. AB - As part of quality assessment of a teleradiology program we evaluated the validity of patient information received, the quality of panoramic radiography imaging in Laos, and the ability of a Laotian radiologist to detect temporomandibular joint abnormalities. The amount of patient information gathered from 2,021 scans of panoramic radiographs was evaluated by triage before image diagnosis. Among the radiographs from 2,021 patients, primary triage indicated that there was insufficient information for 794 (39.3%) patients. Secondary triage to assess imaging failure included 1,227 radiographs, four of which were excluded from imaging diagnosis because of unacceptable image flaws. In total, 2,446 joints from 1,223 radiographs were evaluated for temporomandibular joint abnormalities in order to compare the image interpretation abilities of Laotian and Japanese radiologists. The kappa coefficient was 0.836 (P < 0.01) for the agreement between the two observers in detecting temporomandibular joint abnormalities on radiographs. We conclude that additional efforts are needed in order to overcome the challenges of maintaining quality in imaging techniques and diagnoses in Laos. PMID- 26369489 TI - A randomized clinical trial of salivary substitute as an adjunct to scaling and root planing for management of periodontal inflammation in mouth breathing patients. AB - We investigated the outcome of conventional periodontal treatment in mouth breathing patients with chronic periodontitis, and compared the efficacy of applying salivary substitute to the anterior sextants as an adjunct to conventional treatment in such patients. In this randomized, investigator-blind, clinical study involving parallel groups, 40 mouth breathing patients were divided into two groups: a control group (CG, n = 20) comprising patients who received scaling and root planing (SRP), and a test group (TG, n = 20) who received salivary substitute as an adjunct to SRP for treatment of chronic periodontitis. The patients were followed up at various time intervals, and improvement of the gingival index (GI) was examined as the primary outcome. Student's t-test, repeated-measures ANOVA and Mann-Whitney U test were applied for statistical analysis. Although periodontal parameters were improved in both groups after 8 weeks of follow-up, the test group showed better improvement in terms of GI and percentage bleeding on probing. Within the limits of this study, our results suggest that the use of salivary substitute has a beneficial adjunctive effect for improvement of periodontal parameters in mouth breathing patients with chronic periodontitis. PMID- 26369490 TI - Compliance with supportive periodontal therapy among patients with aggressive and chronic periodontitis. AB - Compliance with supportive periodontal therapy (SPT) depends on many factors but is generally poor. We compared SPT compliance among patients with aggressive and chronic periodontitis. This single-center longitudinal observational study enrolled 101 patients with generalized aggressive periodontitis (GAP; n = 52) or generalized chronic periodontitis (GCP; n = 49) to compare SPT compliance. All participants were studied for 1 year before the close of data collection. Compliance was classified as complete (100% of programmed visits), erratic (>=50% of programmed visits), or noncompliant (<50% of programmed visits). The proportion of compliant participants was greater among patients with GAP (57.7%) than among those with GCP (30.6%) (P < 0.003); 44.9% of patients with GCP and 15.4% of those with GAP were noncompliant. Compliance was significantly associated with age and sex among patients with GAP. In conclusion, SPT compliance was better in patients with GAP than in those with GCP. Patient attitude and self-belief appear to be important factors in SPT compliance. PMID- 26369491 TI - Fracture strength of ceramic monolithic crown systems of different thickness. AB - The objective of this study was to evaluate fracture strength of high-translucent (HTZ) and low-translucent (LTZ) zirconia and glass-ceramic (LDS) crowns. HTZ and LTZ crowns were made with thicknesses of; 0.3 mm, 0.5 mm, 0.7 mm, 1.0 mm, and 1.5 mm; and LDS crowns of 1.0 mm and 1.5 mm thicknesses. Each group consisted of 10 crowns. All crowns underwent artificial aging before loading until fracture. Mean fracture strengths varied from 450 N to 3,248 N in the LTZ group, 438 N to 3,487 N in the HTZ group, and 1,030 N to 1,431 N in the LDS group. The load at fracture of HTZ and LTZ crowns was equal. The load at fracture of yttria-stabilized tetragonal zirconia polycrystals crowns was significantly greater than LDS crowns (P = 0.000). Two types of fractures were recorded; complete and partial crack like fracture. The crack type fracture occurred most frequently in all groups except in the thicker LTZ groups (1.0 mm and 1.5 mm). According to this study, there is no difference in strength between crowns made of high-translucent or low translucent zirconia. At equal thickness, the strength of zirconia crowns was significantly greater than that of lithium-disilicate glass-ceramic. PMID- 26369492 TI - Perceptions regarding the occurrence and prevention of orofacial injuries during general anesthesia. AB - Orofacial trauma can occur during general anesthesia. Protective measures should be taken to prevent or minimize such injuries. We evaluated perceptions regarding the occurrence and prevention of orofacial injuries during general anesthesia among 74 professionals who perform this procedure. All participants were from Rio de Janeiro, Brazil, and information was collected in interviews, using a semi structured questionnaire administered during an academic conference. The data were tabulated and analyzed, frequencies were calculated, and the chi-square test (P < 0.05) was used to assess relationships between variables of interest. Most participants (77.0%) had witnessed orofacial trauma during general anesthesia, and the most frequent type of dental injury was fracture (54.4%). Although most participants (64.9%) considered mouthguard use to be important during such procedures, only three reported using mouthguards to protect against patient injury. The likelihood of a dentist referral after injury was significantly associated with participant age (P = 0.03), length of time since graduation (P = 0.02), and area of specialization (P <= 0.01). Although most participants had witnessed orofacial injuries, mouthguards were not routinely used for injury prevention. PMID- 26369493 TI - Dental technician pneumoconiosis mimicking lung cancer. AB - A 47-year-old man was referred for assessment of bilateral lymph node enlargement identified on a routine chest radiograph. Positron emission tomography showed high standardized uptake values (SUVmax: 20.5) in right supraclavicular, right intercostal, and multiple mediastinal lymph nodes. Biopsy samples obtained from the right upper and left lower paratracheal nodes by mediastinoscopy revealed granulomatous inflammation. Clinical and laboratory findings indicated a diagnosis of dental technician pneumoconiosis. The patient is alive and well 3 years after diagnosis. This case highlights the importance of obtaining an occupational history. PMID- 26369494 TI - Eight-year follow-up of autogenous tooth transplantation involving multidisciplinary treatment. AB - Although autogenous tooth transplantation is a widely reported procedure, its success is dependent on a number of factors. Here we describe the surgical technique, endodontic treatment and rehabilitation employed for a patient in whom a lower right third molar was transplanted to substitute an adjacent second molar with extensive caries. During an 8-year follow-up period, normal periodontal healing was observed and no infection, ankylosis or progressive resorption occurred. It may be concluded that transplantation of a third molar is a practicable approach for replacement of a lost permanent tooth, with restoration of esthetics and function. PMID- 26369495 TI - Bevacizumab treatment for symptomatic spinal ependymomas in neurofibromatosis type 2. AB - BACKGROUND: Neurofibromatosis type 2 (NF2) is a tumor suppressor syndrome associated with vestibular schwannomas, meningiomas, and spinal ependymomas. There have been anecdotal reports of radiographic response of spinal ependymomas in NF2 patients being treated for progressive vestibular schwannomas with bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF). AIMS: The aim of this study was to review the clinical effects of bevacizumab treatment for symptomatic, NF2-associated ependymomas METHODS: We conducted a retrospective review of all patients with NF2 treated with bevacizumab for symptomatic ependymoma at three NF2 specialty centers. Tumor size was evaluated by linear measurements; radiographic response was defined as >20% reduction in tumor size. We also performed immunohistochemical evaluation of NF2 associated symptomatic ependymomas from five patients, including two from this clinical series. RESULTS: Eight patients with NF2 and symptomatic ependymoma were treated with bevacizumab. All patients had subjective clinical improvement with bevacizumab, although only five of eight patients evaluated had radiographic response. All tumors expressed VEGF-R2. Four of five evaluated ependymomas expressed VEGF-R1; one without VEGF-R1 expression was from a patient who showed clinical but not radiographic response. CONCLUSIONS: Treatment using bevacizumab improved symptoms related to NF2-associated ependymomas, often without concurrent radiographic response. This treatment effect may be related to VEGF-R1 expression in NF2-associated ependymoma. PMID- 26369496 TI - Morphostructural analysis of the male reproductive system and DNA barcoding in Balclutha brevis Lindberg 1954 (Homoptera, Cicadellidae). AB - Balclutha brevis Lindberg 1954 is an allochthonous leafhopper infesting an invasive grass, Pennisetum setaceum, in Sicily and in mainland Europe; therefore, this species could compete with populations of native species, thus contributing to the loss of biodiversity. Considering the ecological implications of B. brevis, investigations on all its biological aspects represent, therefore, a premise for further studies in applied sciences. Based on the lacking ultrastructural data about the reproductive systems of the Auchenorrhyncha, we carried out morphostructural investigations on the male reproductive system of B. brevis. Further, a first report of DNA barcoding analysis (amplification and sequencing of Cytochrome Oxidase I gene) has also been performed to characterize B. brevis compared to other congeneric species. From a morphological point of view, the male reproductive system of B. brevis has an organization comparable to the general anatomical features of most of the Auchenorrhyncha species; however, comparing our data with those concerning the different groups of Cicadomorpha, some considerations are discussed. As for the histological and ultrastructural investigations, our results show a secretory activity of the various examined structures, mainly in the lateral ejaculatory ducts and in the accessory glands. The latter, in particular, show morphostructural differences comparing the distal tract to the proximal one; moreover, the histochemical techniques showed the possible presence of a lipid component in the peculiar cytoplasmic granules found in the gland cells. The significance of these findings in the accessory glands is discussed. Finally, the ultrastructural features found in the seminal vesicles are different from those of the lateral ejaculatory ducts and are indicative of the different roles played by these structures in the organization of the spermatozoa bundles. PMID- 26369497 TI - Ultrastructural insights into tomato infections caused by three different pathotypes of Pepino mosaic virus and immunolocalization of viral coat proteins. AB - This paper presents studies on an ultrastructural analysis of plant tissue infected with different pathotypes of Pepino mosaic virus (PepMV) and the immunolocalization of viral coat proteins. Because the PepMV virus replicates with a high mutation rate and exhibits significant genetic diversity, therefore, isolates of PepMV display a wide range of symptoms on infected plants. In this work, tomato plants of the Beta Lux cultivar were inoculated mechanically with three pathotypes representing the Chilean 2 (CH2) genotype: mild (PepMV-P22), necrotic (PepMV-P19) and yellowing (PepMV-P5-IY). The presence of viral particles in all infected plants in the different compartments of various cell types (i.e. spongy and palisade mesophyll, sieve elements and xylem vessels) was revealed via ultrastructural analyses. For the first time, it was possible to demonstrate the presence of crystalline inclusions, composed of virus-like particles. In the later stage of PepMV infection (14 dpi) various pathotype-dependent changes in the structure of the individual organelles (i.e. mitochondria, chloroplasts) were found. The strongest immunogold labeling of the viral coat proteins was also observed in plants infected by necrotic isolates. A large number of viral coat proteins were marked in the plant conductive elements, both xylem and phloem. PMID- 26369498 TI - Evaluation of hepatitis B virus transmission and antiviral therapy among hepatitis B surface antigen-positive pregnant women. AB - AIM: The aim of the present study was to assess the potential risk of hepatitis B virus (HBV) vertical transmission among Turkish parturient women and to evaluate the efficacy and safety of antiviral agents. MATERIAL AND METHODS: Data were collected retrospectively from 114 HBV-infected pregnant women and their infants in eight health institutions in Turkey. RESULTS: The baseline characteristics of the women were: mean age, 28.3 +/- 5.2 years; alanine aminotransferase, 57.4 +/- 139.0 U/L; aspartate aminotransferase, 56.6 +/- 150.0 U/L; and HBV DNA, 8.3 * 10(7) +/- 2.6 * 10(8) copies/mL. Family history of HBV infection was detected in 53.5% (n = 61). In total, 60 (52.6%) pregnant women received tenofovir (60.0%), lamivudine (33.3%) or telbivudine (6.7%) therapy at the median gestational age of 22.2 +/- 8.5 (1-36) weeks. All infants were vaccinated and hepatitis B immune globulin was administered, with 81 of them (71.1%) available for follow-up. After completion of HBV vaccination course, 71 (87.7%) infants had protective anti-HBs levels, three (3.7%) were hepatitis B surface antigen-positive, and seven (8.6%) were hepatitis B surface antigen-negative with nonprotective anti-HBs levels. Five of the infants had low gestational birthweight but no other birth defects were observed. CONCLUSION: According to our results, viral load may not be the only effecting factor for transmission of HBV to children of infected mothers. Pregnant women with high viral load should be followed-up closely during pregnancy. They should begin to take tenofovir or telbivudine, which are category B drugs for pregnancy, at the beginning of the third trimester at the latest. We need new treatment strategies; and close follow-up of mothers and children is another important issue. PMID- 26369499 TI - Animal movements in the Kenya Rift and evidence for the earliest ambush hunting by hominins. AB - Animal movements in the Kenya Rift Valley today are influenced by a combination of topography and trace nutrient distribution. These patterns would have been the same in the past when hominins inhabited the area. We use this approach to create a landscape reconstruction of Olorgesailie, a key site in the East African Rift with abundant evidence of large-mammal butchery between ~1.2 and ~0.5 Ma BP. The site location in relation to limited animal routes through the area show that hominins were aware of animal movements and used the location for ambush hunting during the Lower to Middle Pleistocene. These features explain the importance of Olorgesailie as a preferred location of repeated hominin activity through multiple changes in climate and local environmental conditions, and provide insights into the cognitive and hunting abilities of Homo erectus while indicating that their activities at the site were aimed at hunting, rather than scavenging. PMID- 26369500 TI - Introduction to the Special Issue Estradiol and Cognition: Molecules to Mind. PMID- 26369501 TI - PCSK9 Inhibitors: Are We on the Verge of a Breakthrough? AB - Statins are first-line therapy for lowering cholesterol and reducing cardiovascular events. A significant need for new lipid-modifying therapies remains for patients unable to tolerate statins or achieve guideline-based cholesterol targets. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key regulator of LDL receptor recycling. Gain-of-function PCSK9 mutations are associated with high low-density lipoprotein cholesterol (LDL-C) levels and increased risk of coronary artery disease, while loss-of-function variants result in low LDL-C and decreased risk of cardiovascular events. PCSK9 monoclonal antibody inhibitors have been developed and lower LDL-C levels up to 70% in clinical trials. These inhibitors are well tolerated, with low serious adverse event rates. Phase III clinical outcome trials with these agents are ongoing and will determine their efficacy in reducing cardiovascular events and address long term safety concerns. PMID- 26369502 TI - Optimal Temperature for Radiofrequency Ablation of Lumbar Medial Branches for Treatment of Facet-Mediated Back Pain. AB - BACKGROUND: Radiofrequency ablation (RFA) of the medial branch nerves that innervate the facet joints is a well-established treatment modality; however, studies to determine the optimal radiofrequency ablation temperature are lacking. A wide range (70 to 90 degrees C) has been used. This study aimed to compare outcomes with two set temperatures for the lumbar facet medial branch ablation, 90 and 80 degrees C. METHODS: This retrospective study compared the degree of patient self-reported functional improvement relief, postoperative opioid dose changes, as well as duration among lumbar facet medial branch (RFA) patients who had the procedures performed at 80 or 90 degrees C. RESULTS: Patients who underwent the procedure at 90 degrees C had 3.1 (95% CI 1.7, 6.5) times the odds (P = 0.0004) of reporting functional improvement of at least 50% when compared to those who underwent neurotomy at 80 degrees C. For self-reported functional improvement greater or equal to 75%, the results were sustained with an odds ratio of 2.8 (95% CI 1.2, 5.7) favoring those with 90 degrees C temperature neurotomy (P = 0.002). CONCLUSION: There seems to be significant functional improvement associated with temp of 90 degrees C compared to 80 degrees C, with no added risk of complications. Randomized controlled studies are warranted. PMID- 26369503 TI - Solar forcing synchronizes decadal North Atlantic climate variability. AB - Quasi-decadal variability in solar irradiance has been suggested to exert a substantial effect on Earth's regional climate. In the North Atlantic sector, the 11-year solar signal has been proposed to project onto a pattern resembling the North Atlantic Oscillation (NAO), with a lag of a few years due to ocean atmosphere interactions. The solar/NAO relationship is, however, highly misrepresented in climate model simulations with realistic observed forcings. In addition, its detection is particularly complicated since NAO quasi-decadal fluctuations can be intrinsically generated by the coupled ocean-atmosphere system. Here we compare two multi-decadal ocean-atmosphere chemistry-climate simulations with and without solar forcing variability. While the experiment including solar variability simulates a 1-2-year lagged solar/NAO relationship, comparison of both experiments suggests that the 11-year solar cycle synchronizes quasi-decadal NAO variability intrinsic to the model. The synchronization is consistent with the downward propagation of the solar signal from the stratosphere to the surface. PMID- 26369504 TI - Urinary incontinence and other pelvic floor dysfunctions in female athletes in Brazil: A cross-sectional study. AB - The pelvic floor (PF) provides support to all pelvic organs, as well as appropriately closure/opening mechanism of the urethra, vagina, and anus. Therefore, it is likely that female athletes involved in high-impact and in strong-effort activities are at risk for the occurrence of urinary incontinence (UI). This study aimed to investigate the occurrence of UI and other PF dysfunctions (PFD) [anal incontinence (AI), symptoms of constipation, dyspareunia, vaginal laxity, and pelvic organ prolapse] in 67 amateur athletes (AT) compared with a group 96 of nonathletes (NAT). An ad hoc survey based on questions from reliable and valid instruments was developed to investigate the occurrence of PFD symptoms. The risk of UI was higher in AT group (odds ratio: 2.90; 95% CI: 1.50-5.61), mostly among artistic gymnastics and trampoline, followed by swimming and judo athletes. Whereas, AT group reported less straining to evacuate (OR: 0.46; 95% CI: 0.22-0.96), manual assistance to defecate (OR: 0.24; 95% CI: 0.05-1.12), and a higher stool frequency (OR: 0.29; 95% CI: 0.13 0.64) than NAT group. The occurrence of loss of gas and sexual symptoms was high for both groups when compared with literature, although with no statistical difference between them. Pelvic organ prolapse was only reported by nonathletes. Athletes are at higher risk to develop UI, loss of gas, and sexual dysfunctions, either practicing high-impact or strong-effort activities. Thus, pelvic floor must be considered as an entity and addressed as well. Also, women involved in long-term high-impact and strengthening sports should be advised of the impact of such activities on pelvic floor function and offered preventive PFD strategies as well. PMID- 26369509 TI - Dementia: Researchers urge more dementia studies to focus on prevention rather than cure. PMID- 26369510 TI - Movement disorders: Repurposing riluzole to treat hereditary cerebellar ataxia. PMID- 26369507 TI - Circulating biomarkers for gliomas. AB - Currently, gliomas are diagnosed by neuroimaging, and refined diagnosis requires resection or biopsy to obtain tumour tissue for histopathological classification and grading. Blood-derived biomarkers, therefore, would be useful as minimally invasive markers that could support diagnosis and enable monitoring of tumour growth and response to treatment. Such circulating biomarkers could distinguish true progression from therapy-associated changes such as radiation necrosis, and help evaluate the persistence or disappearance of a therapeutic target, such as an oncoprotein or a targetable gene mutation, after targeted therapy. Unlike for other tumours, circulating biomarkers for gliomas are still being defined and are not yet in use in clinical practice. Circulating tumour DNA (ctDNA) isolated from plasma has been shown to reflect the mutational status of glioblastoma, and extracellular vesicles (EVs) containing ctDNA, microRNA and proteins function as rapidly adapting reservoirs for glioma biomarkers such as typical DNA mutations, regulatory microRNAs and oncoproteins. Ideally, circulating tumour cells could enable profiling of the whole-tumour genome, but they are difficult to detect and can reflect only a single cell type of the heterogeneous tumour composition, whereas EVs reflect the complex heterogeneity of the whole tumour, as well as its adaptations to therapy. Although all categories of potential blood-derived biomarkers need to be developed further, findings from other tumour types suggest that EVs are the most promising biomarkers. PMID- 26369513 TI - Dementia: Cerebrospinal fluid biomarkers in dementias. AB - A new study describes a biomarker profile based on cerebrospinal fluid (CSF) tau and amyloid-beta1-42 in a uniquely large population with a variety of dementia diagnoses. This study confirms the differential diagnostic value of CSF biomarkers and further highlights the important neuropathological overlap between dementia aetiologies. PMID- 26369515 TI - Polyneuritis cranialis--subtype of Guillain-Barre syndrome? PMID- 26369511 TI - Evidence-based guidelines: MAGNIMS consensus guidelines on the use of MRI in multiple sclerosis--establishing disease prognosis and monitoring patients. AB - The role of MRI in the assessment of multiple sclerosis (MS) goes far beyond the diagnostic process. MRI techniques can be used as regular monitoring to help stage patients with MS and measure disease progression. MRI can also be used to measure lesion burden, thus providing useful information for the prediction of long-term disability. With the introduction of a new generation of immunomodulatory and/or immunosuppressive drugs for the treatment of MS, MRI also makes an important contribution to the monitoring of treatment, and can be used to determine baseline tissue damage and detect subsequent repair. This use of MRI can help predict treatment response and assess the efficacy and safety of new therapies. In the second part of the MAGNIMS (Magnetic Resonance Imaging in MS) network's guidelines on the use of MRI in MS, we focus on the implementation of this technique in prognostic and monitoring tasks. We present recommendations on how and when to use MRI for disease monitoring, and discuss some promising MRI approaches that may be introduced into clinical practice in the near future. PMID- 26369520 TI - Epilepsy: Intriguing new data on epilepsy and risks at delivery. AB - A large study from the USA suggests that epilepsy in pregnant women elevates the risk of adverse events both to the mother and the fetus, including an 11-fold increase in the risk of death of the mother at delivery. Although the data are intriguing, the study has caveats that call for cautious interpretation. PMID- 26369516 TI - Ocular motor signatures of cognitive dysfunction in multiple sclerosis. AB - The anatomical and functional overlap between ocular motor command circuitry and the higher-order networks that form the scaffolding for cognition makes for a compelling hypothesis that measures of ocular motility could provide a means to sensitively interrogate cognitive dysfunction in people with multiple sclerosis (MS). Such an approach may ultimately provide objective and reproducible measures of cognitive dysfunction that offer an innovative capability to refine diagnosis, improve prognostication, and more accurately codify disease burden. A further dividend may be the validation and application of biomarkers that can be used in studies aimed at identifying and monitoring preventative, protective and even restorative properties of novel neurotherapeutics in MS. This Review discusses the utility of ocular motor measures in patients with MS to characterize disruption to wide-ranging networks that support cognitive function. PMID- 26369521 TI - "Know What to Do If You Encounter a Flash Flood": Mental Models Analysis for Improving Flash Flood Risk Communication and Public Decision Making. AB - Understanding how people view flash flood risks can help improve risk communication, ultimately improving outcomes. This article analyzes data from 26 mental models interviews about flash floods with members of the public in Boulder, Colorado, to understand their perspectives on flash flood risks and mitigation. The analysis includes a comparison between public and professional perspectives by referencing a companion mental models study of Boulder-area professionals. A mental models approach can help to diagnose what people already know about flash flood risks and responses, as well as any critical gaps in their knowledge that might be addressed through improved risk communication. A few public interviewees mentioned most of the key concepts discussed by professionals as important for flash flood warning decision making. However, most interviewees exhibited some incomplete understandings and misconceptions about aspects of flash flood development and exposure, effects, or mitigation that may lead to ineffective warning decisions when a flash flood threatens. These include important misunderstandings about the rapid evolution of flash floods, the speed of water in flash floods, the locations and times that pose the greatest flash flood risk in Boulder, the value of situational awareness and environmental cues, and the most appropriate responses when a flash flood threatens. The findings point to recommendations for ways to improve risk communication, over the long term and when an event threatens, to help people quickly recognize and understand threats, obtain needed information, and make informed decisions in complex, rapidly evolving extreme weather events such as flash floods. PMID- 26369523 TI - Fixed drug eruption due to acyclovir, valacyclovir and famciclovir. PMID- 26369522 TI - The effect of heterotopic noxious conditioning stimulation on Adelta-, C- and Abeta-fibre brain responses in humans. AB - Human studies have shown that heterotopic nociceptive conditioning stimulation (HNCS) applied to a given body location reduces the percept and brain responses elicited by noxious test stimuli delivered at a remote body location. It remains unclear to what extent this effect of HNCS relies on the spinal-bulbar-spinal loop mediating the effect of diffuse noxious inhibitory controls (DNICs) described in animals, and/or on top-down cortical mechanisms modulating nociception. Importantly, some studies have examined the effects of HNCS on the brain responses to nociceptive input conveyed by Adelta-fibres. In contrast, no studies have explored the effects of HNCS on the responses to selective nociceptive C-fibre input and non-nociceptive Abeta-fibre input. In this study, we measured the intensity of perception and event-related potentials (ERPs) to stimuli activating Adelta-, C- and Abeta-fibres, before, during and after HNCS, obtained by immersing one foot in painful cold water. We observed that (i) the perceived intensity of nociceptive Adelta- and C-stimuli was reduced during HNCS, and (ii) the ERPs elicited by Adelta- and Abeta- and C-stimuli were also reduced during HNCS. Importantly, because Abeta-ERPs are related to primary afferents that ascend directly through the dorsal columns without being relayed at spinal level, the modulation of these responses may not be explained by an influence of descending projections modulating the transmission of nociceptive input at spinal level. Therefore, our results indicate that, in humans, HNCS should be used with caution as a direct measure of DNIC-related mechanisms. PMID- 26369524 TI - Long-term outcome of severe acute kidney injury survivors followed by nephrologists in a developing country. AB - AIM: This study aimed to evaluate the long-term outcome of patients after a severe episode of acute kidney injury (AKI) on survival and progression to chronic kidney disease (CKD) and to identify risk factors associated with these outcomes. METHODS: We performed a prospective study that evaluated the long-term outcome of 509 AKI stage 3 patients who were followed by nephrologists in a Brazilian University Hospital from 2004 to 2013. RESULTS: Age was 60.2 years (47.5-71) and the follow-up time was 25 months (12-44). The late mortality was 38.1% and age (HR 2.89, 95% CI=1.88 to 4.46, P < 0.0001), diabetes (HR 1.46, 95% CI=1 0.02 to 2.16, P < 0.047), liver disease (HR 2.95, 95% CI=1.19 to 7.3, P = 0.02) and creatinine (Cr) at the time of hospital discharge (HR 1.21, 95% CI=1.04 to 1.41, P = 0.01) were associated with poor long-term survival. At the moment of hospital discharge, 52.1% of patients had complete recovery of renal function, 39.7% had partial recovery and 8.3% had not recovered renal function. After 36 months, 43.5% of patients progressed to CKD, and 5.3% needed for chronic dialysis. Factors associated with progression to CKD were age (HR 1.02, 95% CI=1.008 to 1.035, P = 0.009), CKD (HR 1.05 95% CI=1.007 to 1.09, P = 0.04), diabetes (HR 1.12, CI 1.008-1.035, P = 0.009) and number of AKI episodes (HR 1.65, 95% CI=1.19 to 2.2, P = 0.0023). CONCLUSION: This study showed that AKI patients have high mortality after hospital discharge and age, diabetes, liver disease, and Cr value at the time of discharge were factors associated with long term mortality. The risk factors for this progression to CKD were age, the presence of diabetes and the number of AKI episodes. PMID- 26369525 TI - Heterogeneous populations in non-ischaemic cardiogenic shock. PMID- 26369526 TI - CD25 blockade in kidney transplant patients randomized to standard-dose or high dose basiliximab with cyclosporine, or high-dose basiliximab in a calcineurin inhibitor-free regimen. AB - An increased basiliximab dose may saturate T-cell CD25 receptors in kidney transplant patients receiving calcineurin inhibitor (CNI)-free immunosuppression. In a 12-week study, 16 de novo kidney transplant patients were randomized to (i) 40 mg basiliximab with cyclosporine [n = 3] (controls), (ii) 80 mg basiliximab with cyclosporine [n = 6], or (iii) 80 mg basiliximab with everolimus (CNI-free) [n = 7], all with mycophenolic acid and steroids. Recruitment was stopped prematurely due to increased biopsy-proven acute rejection (BPAR) in the basiliximab 80 mg CNI-free group. BPAR occurred in 1/3, 1/6, and 4/7 patients in the three treatment groups, respectively. The primary endpoint, area under the effect curve of CD25 saturation to week 12, was 8.4(1.6) % * weeks in the control group, 11.1(1.1) % * weeks with basiliximab 80 mg + cyclosporine, and 9.7(0.7) % * weeks in the basiliximab 80 mg CNI-free group (P = 0.020 for basiliximab 80 mg + cyclosporine versus controls; P = 0.119 for basiliximab 80 mg CNI-free versus controls). Although small patient numbers prohibit robust conclusions, these results suggest that doubling the cumulative basiliximab dose to 80 mg does not provide adequate immunosuppression during the first 3 months after kidney transplantation in the absence of CNI therapy (ClinicalTrials.gov number: NCT01596062). PMID- 26369528 TI - Validation of Six Nomograms for Predicting Non-sentinel Lymph Node Metastases in a Dutch Breast Cancer Population. AB - BACKGROUND: The usefulness of axillary lymph node dissection (ALND) in patients with positive sentinel nodes (SN) is still an ongoing debate. Several nomograms have been developed for predicting non-sentinel lymph node metastases (NSLNM). We validated six nomograms using data from 10 years of breast cancer surgery in our hospital. METHODS: We retrospectively analyzed all patients with a proven breast malignancy and a SN procedure between 2001 and 2011 in our hospital. RESULTS: Data from 1084 patients were reviewed; 260 (24 %) had a positive SN. No patients with isolated tumor cells, 6 patients (8 %) with micrometastases, and 65 patients (41 %) with macrometastases had additional axillary NSLNM. In 2 patients (3 %) with micrometastases, the ALND influenced postoperative treatment. In the group of patients with macrometastases tumor size >2 cm, extranodal growth and having no negative SNs were predictors of NSLNM. The revised MD Anderson Cancer Center and Helsinki nomograms performed the best, with an area under the curve value of 0.78. CONCLUSIONS: ALND could probably be safely omitted in most patients with micrometastases but is still indicated in patients with macrometastases, especially in patients with tumor size >2 cm, extranodal growth, and no negative SNs. The revised MD Anderson Cancer Center and Helsinki nomograms were the most predictive in our patient group. PMID- 26369527 TI - Genotype-phenotype correlation and course of transthyretin familial amyloid polyneuropathies in France. AB - OBJECTIVE: To compare the natural history of familial transthyretin amyloid polyneuropathies (FAP) due to the Val30Met, Ser77Tyr, and Ile107Val mutations in France with the classical Portuguese Val30Met FAP. METHODS: We compared 84 French patients with a control group of 110 Portuguese patients carrying the Val30Met mutation also living in France, all referred to and followed at the French National FAP Reference Center from 1988 to 2010. Clinical examination, functional and walking disability scores, nerve conduction studies, and muscle biopsies are reported. We also conducted a comprehensive literature review to further determine the range of phenotypic expression. RESULTS: By comparison with Portuguese Val30Met FAP, French Ile107Val, Ser77Tyr, and LateVal30Met FAP showed more rapid and severe disease progression; onset of gait disorders was 3 times more rapid (p < 0.0001) and the rate of modified Norris test decline was up to 40 times faster in Ile107Val patients (p < 0.0001). Median survival was much shorter in Ile107Val and in Val30Met mutation with late onset (>50 years; LateMet30) FAP (p = 0.0005). Other distinctive features relative to the Portuguese patients included atypical clinical presentations, demyelination on nerve conduction studies (p = 0.0005), and difficult identification of amyloid deposits in nerve and muscle biopsies. INTERPRETATION: Ile107Val and LateMet30 mutations are associated with the most debilitating and severe FAP ever described, with rapid onset of tetraparesis and shorter median survival. It could be explained by frequent large-fiber involvement and associated demyelination and more severe axonal loss. These findings have major implications for genetic counseling and patient management as new therapeutic options are being assessed in clinical trials (TTR gene silencing). PMID- 26369529 TI - [Toxic megacolon]. AB - BACKGROUND: Toxic megacolon constitutes a feared, life-threatening complication of severe intestinal inflammation and is a challenge for interdisciplinary medical care. OBJECTIVES: Specific aspects of conservative treatment based on current scientific evidence derived from guidelines, qualified reviews, and scientific studies are presented, which provide a rational approach and maximize therapeutic success. MATERIALS AND METHODS: This work is based on a selective literature review and the authors' experience of many years in gastroenterology and intensive care. RESULTS: Toxic megacolon requires a rapid interdisciplinary assessment. Depending on the underlying etiology, an individual treatment concept needs to be developed. If an infectious or inflammatory cause is probable, a conservative approach can reduce perioperative morbidity and mortality. A step wise approach with controlled reevaluations of the response to therapy after 72 h and 7 days avoids uncontrolled delay of surgical options further ensuring patient safety. CONCLUSION: Despite a decreasing incidence of toxic megacolon, it remains an interdisciplinary therapeutic challenge. PMID- 26369530 TI - Cysteine-rich secretory protein 3 plays a role in prostate cancer cell invasion and affects expression of PSA and ANXA1. AB - Cysteine-rich secretory protein 3 (CRISP-3) is upregulated in prostate cancer as compared to the normal prostate tissue. Higher expression of CRISP-3 has been linked to poor prognosis and hence it has been thought to act as a prognostic marker for prostate cancer. It is proposed to have a role in innate immunity but its role in prostate cancer is still unknown. In order to understand its function, its expression was stably knocked down in LNCaP cells. CRISP-3 knockdown did not affect cell viability but resulted in reduced invasiveness. Global gene expression changes upon CRISP-3 knockdown were identified by microarray analysis. Microarray data were quantitatively validated by evaluating the expression of seven candidate genes in three independent stable clones. Functional annotation of the differentially expressed genes identified cell adhesion, cell motility, and ion transport to be affected among other biological processes. Prostate-specific antigen (PSA, also known as Kallikrein 3) was the top most downregulated gene whose expression was also validated at protein level. Interestingly, expression of Annexin A1 (ANXA1), a known anti-inflammatory protein, was upregulated upon CRISP-3 knockdown. Re-introduction of CRISP-3 into the knockdown clone reversed the effect on invasiveness and also led to increased PSA expression. These results suggest that overexpression of CRISP-3 in prostate tumor may maintain higher PSA expression and lower ANXA1 expression. Our data also indicate that poor prognosis associated with higher CRISP-3 expression could be due to its role in cell invasion. PMID- 26369531 TI - Activation of canonical Wnt/beta-catenin signaling inhibits H2O2-induced decreases in proliferation and differentiation of human periodontal ligament fibroblasts. AB - Human periodontal ligament fibroblasts (hPLFs) are exposed to oxidative stress during periodontal inflammation and dental treatments. It is hypothesized that hydrogen peroxide (H2O2)-mediated oxidative stress decreases survival and osteogenic differentiation of hPLFs, whereas these decreases are prevented by activation of the Wnt pathway. However, there has been a lack of reports that define the exact roles of canonical Wnt/beta-catenin signaling in H2O2-exposed hPLFs. Treatment with H2O2 reduced viability and proliferation in hPLFs in a dose and time-dependent manner and led to mitochondria-mediated apoptosis. Pretreatment with lithium chloride (LiCl) or Wnt1 inhibited the oxidative damage that occurred in H2O2-exposed hPLFs. However, knockout of beta-catenin or treatment with DKK1 facilitated the H2O2-induced decreases in viability, mitochondrial membrane potential, and Bcl-2 induction. Osteoblastic differentiation of hPLFs was also inhibited by combined treatment with 100 MUM H2O2, as evidenced by the decreases in alkaline phosphatase (ALP) activity and mineralization. H2O2-mediated inhibition of osteoblast differentiation in hPLFs was significantly attenuated in the presence of 500 ng/ml Wnt1 or 20 mM LiCl. In particular, H2O2 stimulated the expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) at protein and mRNA levels in hPLFs, whereas the induction was almost completely suppressed in the presence of Wnt1 or LiCl. Furthermore, siRNA mediated silencing of Nrf2 blocked H2O2-induced decreases in ALP activity and mineralization of hPLFs with the concomitant restoration of runt-related transcription factor 2 and osteocalcin mRNA expression and ALP activity. Collectively, these results suggest that activation of the Wnt/beta-catenin pathway improves proliferation and mineralization in H2O2-exposed hPLFs by downregulating Nrf2. PMID- 26369532 TI - Computational investigation of molecular mechanism and neuropathological implications in Huntington disease. AB - Huntington's disorder (HD), caused by mutations of the IT-15 gene, is an autosomal genetic disease that causes the breakdown of the nerve cells in the brain. The IT-15 gene encodes the huntingtin (Htt) protein. Htt, along with its interacting partners, are involved in maintaining proper communication among neurons. Our work is based on the interaction behavior between Htt (in three polyglutamine (polyQ) states that is Htt 0Q, 17Q and 36Q) and SH3GL3 interacting protein by using computational methods. We used the HADDOCK docking platform to find out the extent of interaction between Htt polyQ models and SH3GL3. The Htt36Q (mutated) showed higher interaction than Htt17Q (native) with SH3GL3. Molecular dynamics simulation was performed to uncover the structural fluctuations of polyQ models and their complexes. RMSD, Rg, SASA, and total interaction energy graph showed significant results, where as mutant Htt showed higher fluctuations and flexibility than native Htt. The increase in the length of polyQ was found to affect the stability, flexibility, and compactness of the protein and its complex. Our research provided a propitious approach to understand the consequence of polyglutamination in Htt and its relation with HD. PMID- 26369533 TI - CYP2D6 genotype- and endoxifen-guided tamoxifen dose escalation increases endoxifen serum concentrations without increasing side effects. AB - Breast cancer patients with absent or reduced CYP2D6 activity and consequently low endoxifen levels may benefit less from tamoxifen treatment. CYP2D6 poor and intermediate metabolizers may need a personalized increased tamoxifen dose to achieve effective endoxifen serum concentrations, without increasing toxicity. From a prospective study population of early breast cancer patients using tamoxifen (CYPTAM: NTR1509), 12 CYP2D6 poor and 12 intermediate metabolizers were selected and included in a one-step tamoxifen dose escalation study during 2 months. The escalated dose was calculated by multiplying the individual's endoxifen level at baseline relative to the average endoxifen concentration observed in CYP2D6 extensive metabolizers by 20 mg (120 mg maximum). Endoxifen levels and tamoxifen toxicity were determined at baseline and after 2 months, just before patients returned to the standard dose of 20 mg. Tamoxifen dose escalation in CYP2D6 poor and intermediate metabolizers significantly increased endoxifen concentrations (p < 0.001; p = 0.002, respectively) without increasing side effects. In intermediate metabolizers, dose escalation increased endoxifen to levels comparable with those observed in extensive metabolizers. In poor metabolizers, the mean endoxifen level increased from 24 to 81 % of the mean concentration in extensive metabolizers. In all patients, the endoxifen threshold of 5.97 ng/ml (=16.0 nM) reported by Madlensky et al. was reached following dose escalation. CYP2D6 genotype- and endoxifen-guided tamoxifen dose escalation increased endoxifen concentrations without increasing short-term side effects. Whether such tamoxifen dose escalation is effective and safe in view of long-term toxic effects is uncertain and needs to be explored. PMID- 26369534 TI - 4-IHC classification of breast cancer subtypes in a large cohort of a clinical cancer registry: use in clinical routine for therapeutic decisions and its effect on survival. AB - The aim of the present study was to evaluate to what extent the combination of standard histopathological parameters determines the biology of breast cancer and the effect on therapy and prognosis. The Clinical Cancer Registry Regensburg (Bavaria, Germany) included n = 4,480 female patients with primary, non metastatic (M0) invasive breast cancer diagnosed between 2000 and 2012. Immuno histochemical analyses, i.e., estrogen receptor (ER), progesterone receptor (PR), HER2, and Ki-67 (4-IHC), defined the tumor biological subtypes Luminal A, Luminal B, HER2-like, and Basal-like. Subtype-related differences in therapies and overall survival (OS) were analyzed using multivariable statistical methods. 4344 patients (97.0 %) could be classified into the four common tumor biological subtypes. The two most frequent entities were Luminal A (48.4 %), Luminal B (24.8 %), HER2-like (17.8 %), and Basal-like subtype (9.0 %). A multivariable Cox regression model showed that the best 7-year OS was seen in Luminal A patients and that OS of Luminal B and HER2-like patients was comparable (HR = 1.59, P < 0.001 versus HR = 1.51, P = 0.03). Lowest OS was seen in patients with Basal-like tumors (HR = 2.18, P < 0.001). In conclusion, the classification of tumor biological subtypes by the ER, PR, HER2, and Ki-67 biomarkers is practical in routine clinical work. Providing that quality assurance of these markers is ensured, this classification is useful for making therapy decisions in the routine clinical management of breast cancer patients. PMID- 26369535 TI - A robust estimation of infliximab pharmacokinetic parameters in Crohn's disease. PMID- 26369536 TI - Drug interaction databases in medical literature: transparency of ownership, funding, classification algorithms, level of documentation, and staff qualifications. A systematic review. AB - PURPOSE: It is well documented that drug-drug interaction databases (DIDs) differ substantially with respect to classification of drug-drug interactions (DDIs). The aim of this study was to study online available transparency of ownership, funding, information, classifications, staff training, and underlying documentation of the five most commonly used open access English language-based online DIDs and the three most commonly used subscription English language-based online DIDs in the literature. METHODS: We conducted a systematic literature search to identify the five most commonly used open access and the three most commonly used subscription DIDs in the medical literature. The following parameters were assessed for each of the databases: Ownership, classification of interactions, primary information sources, and staff qualification. We compared the overall proportion of yes/no answers from open access databases and subscription databases by Fisher's exact test-both prior to and after requesting missing information. RESULTS: Among open access DIDs, 20/60 items could be verified from the webpage directly compared to 24/36 for the subscription DIDs (p = 0.0028). Following personal request, these numbers rose to 22/60 and 30/36, respectively (p < 0.0001). For items within the "classification of interaction" domain, proportions were 3/25 versus 11/15 available from the webpage (P = 0.0001) and 3/25 versus 15/15 (p < 0.0001) available upon personal request. CONCLUSION: Available information on online available transparency of ownership, funding, information, classifications, staff training, and underlying documentation varies substantially among various DIDs. Open access DIDs had a statistically lower score on parameters assessed. PMID- 26369537 TI - Density functional theory calculations on the active site of biotin synthase: mechanism of S transfer from the Fe(2)S(2) cluster and the role of 1st and 2nd sphere residues. AB - Density functional theory (DFT) calculations are performed on the active site of biotin synthase (BS) to investigate the sulfur transfer from the Fe(2)S(2) cluster to dethiobiotin (DTB). The active site is modeled to include both the 1st and 2nd sphere residues. Molecular orbital theory considerations and calculation on smaller models indicate that only an S atom (not S2-) transfer from an oxidized Fe(2)S(2) cluster leads to the formation of biotin from the DTB using two adenosyl radicals generated from S-adenosyl-L-methionine. The calculations on larger protein active site model indicate that a 9-monothiobiotin bound reduced cluster should be an intermediate during the S atom insertion from the Fe(2)S(2) cluster consistent with experimental data. The Arg260 bound to Fe1, being a weaker donor than cysteine bound to Fe(2), determines the geometry and the electronic structure of this intermediate. The formation of this intermediate containing the C9-S bond is estimated to have a DeltaG(?) of 17.1 kcal/mol while its decay by the formation of the 2nd C6-S bond is calculated to have a DeltaG(?) of 29.8 kcal/mol, i.e. the 2nd C-S bond formation is calculated to be the rate determining step in the cycle and it leads to the decay of the Fe(2)S(2) cluster. Significant configuration interaction (CI), present in these transition states, helps lower the barrier of these reactions by ~30-25 kcal/mol relative to a hypothetical outer-sphere reaction. The conserved Phe285 residue near the Fe(2)S(2) active site determines the stereo selectivity at the C6 center of this radical coupling reaction. Reaction mechanism of BS investigated using DFT calculations. Strong CI and the Phe285 residue control the kinetic rate and stereochemistry of the product. PMID- 26369538 TI - Effects of the ruthenium-based drug NAMI-A on the roles played by TGF-beta1 in the metastatic process. AB - The ruthenium-based drug NAMI-A, characterised by its selectivity against solid tumour metastases, promotes TGF-beta1-dependent fibrosis and the reduction of the release of MMPs in the primary tumour. The aim of the study was to examine the interaction of NAMI-A with TGF-beta1 in the process of metastasis formation. NAMI A (1) affects the secretion of TGF-beta1 in metastatic MDA-MB-231 cells rather than in non-tumorigenic HBL-100 cells, (2) prevails over TGF-beta1 with regard to the invasive capacity of the treated cells, and (3) contrasts integrin-dependent migration stimulated by TGF-beta1. It, thus, appears that the effects of NAMI-A on cell invasion and migration are best summarised as an interference with TGF beta1 and a reduction of its activity in these events. At a molecular level, the similar activity of NAMI-A and TGF-beta1 on RhoA GTPase supports its interaction with cell surface integrins while TGF-beta1 can activate it by interaction with its TGFbetaR receptor. The inhibition of TGF-beta1-induced migration of MDA-MB 231 cells by NAMI-A cannot simply be attributed to a modulation of the Smad2 and p38MAPK pathways. In conclusion, the effects of NAMI-A on the biological role of TGF-beta1 in cancer metastasis are insufficient to attribute the responsibility for the anti-metastatic activity of the ruthenium-based drug to this target alone. PMID- 26369540 TI - The Safety and Efficacy of Narrow Band Ultraviolet B Treatment in Dermatology: A Review. AB - Narrow-band ultraviolet B (NBUVB) phototherapy is an important treatment modality in dermatology. The most common dermatological indications for NBUVB include psoriasis, atopic dermatitis and vitiligo; however, it has been found to be an effective and well-tolerated treatment option in various other dermatoses. The efficacy of NBUVB phototherapy compares favorably with other available photo(chemo)therapy options and its efficacy is further augmented by a number of topical and systemic adjuncts. The long-term safety of NBUVB phototherapy remains to be fully elucidated; however, available data now suggest that it is safe and well-tolerated. The objective of this review was to summarize the current understanding of the safety and efficacy of NBUVB phototherapy in dermatology. PMID- 26369539 TI - Investigating the effect of gallium curcumin and gallium diacetylcurcumin complexes on the structure, function and oxidative stability of the peroxidase enzyme and their anticancer and antibacterial activities. AB - Curcumin has a wide spectrum of biological and pharmacological activities including anti-inflammatory, antioxidant, antiproliferative, antimicrobial and anticancer activities. Complexation of curcumin with metals has gained attention in recent years for improvement of its stability. In this study, the effect of gallium curcumin and gallium diacetylcurcumin on the structure, function and oxidative stability of horseradish peroxidase (HRP) enzyme were evaluated by spectroscopic techniques. In addition to the enzymatic investigation, the cytotoxic effect of the complexes was assessed on bladder, MCF-7 breast cancer and LNCaP prostate carcinoma cell lines by MTT assay. Furthermore, antibacterial activity of the complexes against S. aureus and E. coli was explored by dilution test method. The results showed that the complexes improve activity of HRP and also increase its tolerance against the oxidative condition. After addition of the complexes, affinity of HRP for hydrogen peroxide substrate decreases, while the affinity increases for phenol substrate. Circular dichroism, intrinsic and synchronous fluorescence spectra showed that the enzyme structure around the catalytic heme group becomes less compact and also the distance between the heme group and tryptophan residues increases due to binding of the complexes to HRP. On the whole, it can be concluded that the change in the enzyme structure upon binding to the gallium curcumin and gallium diacetylcurcumin complexes results in an increase in the antioxidant efficiency and activity of the peroxidise enzyme. The result of anticancer and antibacterial activities suggested that the complexes exhibit the potential for cancer treatment, but they have no significant antibacterial activity. PMID- 26369541 TI - The Role of Intrinsic Motivation in the Pursuit of Health Science-Related Careers among Youth from Underrepresented Low Socioeconomic Populations. AB - A more diverse health science-related workforce including more underrepresented race/ethnic minorities, especially from low socioeconomic backgrounds, is needed to address health disparities in the USA. To increase such diversity, programs must facilitate youth interest in pursuing a health science-related career (HSRC). Minority youth from low socioeconomic families may focus on the secondary gains of careers, such as high income and status, given their low socioeconomic backgrounds. On the other hand, self-determination theory suggests that it is the intrinsic characteristics of careers which are most likely to sustain pursuit of an HSRC and lead to job satisfaction. Intrinsic and extrinsic motivation for pursuing an HSRC (defined in this study as health professional, health scientist, and medical doctor) was examined in a cohort of youth from the 10th to 12th grade from 2011 to 2013. The sample was from low-income area high schools, had a B- or above grade point average at baseline, and was predominantly: African American (65.7 %) or Hispanic (22.9 %), female (70.1 %), and children of foreign-born parents (64.7 %). In longitudinal general estimating equations, intrinsic motivation (but not extrinsic motivation) consistently predicted intention to pursue an HSRC. This finding provides guidance as to which youth and which qualities of HSRCs might deserve particular attention in efforts to increase diversity in the health science-related workforce. PMID- 26369542 TI - Molecular analysis of hepatitis A virus strains obtained from patients with acute hepatitis A in Mongolia, 2004-2013. AB - Despite the high endemicity of hepatitis A virus (HAV) in Mongolia, the genetic information on those HAV strains is limited. Serum samples obtained from 935 patients with acute hepatitis in Ulaanbaatar, Mongolia during 2004-2013 were tested for the presence of HAV RNA using reverse transcription-PCR with primers targeting the VP1-2B region (481 nucleotides, primer sequences at both ends excluded). Overall, 180 patients (19.3%) had detectable HAV RNA. These 180 isolates shared 94.6-100% identity and formed four phylogenetic clusters within subgenotype IA. One or three representative HAV isolates from each cluster exhibited 2.6-3.9% difference between clusters over the entire genome. Cluster 1 accounted for 65.0% of the total, followed by Cluster 2 (30.6%), Cluster 3 (3.3%), and Cluster 4 (1.1%). Clusters 1 and 2 were predominant throughout the observation period, whereas Cluster 3 was undetectable in 2009 and 2013 and Cluster 4 became undetectable after 2009. The Mongolian HAV isolates were closest to those of Chinese or Japanese origin (97.7-98.5% identities over the entire genome), suggesting the evolution from a common ancestor with those circulating in China and Japan. Further molecular epidemiological analyses of HAV infection are necessary to investigate the factors underlying the spread of HAV and to implement appropriate prevention measures in Mongolia. PMID- 26369543 TI - Protective autophagy promotes the resistance of HER2-positive breast cancer cells to lapatinib. AB - Lapatinib, a tyrosine kinase inhibitor of HER2/EGFR, can inhibit the proliferation of HER2-positive breast cancer cells. Additionally, the combination of lapatinib and chemotherapy can markedly prolong patient survival time. However, the clinical therapeutic effect of lapatinib is severely limited by drug resistance. We previously found that brief treatment with lapatinib induced both apoptosis and autophagy in HER2-positive breast cancer cells. Additionally, the apoptosis induced by lapatinib was dependent on autophagy. In our current study, however, we used extended treatment of HER2-positive breast cancer cells with lapatinib to confirm the presence of protective autophagy in the previously established lapatinib-resistant cells. Specifically, we found that inhibition of autophagy could reduce the proliferation, DNA synthesis, and colony-forming capacity of resistant cells. Thus, autophagy is a potential novel therapeutic target for reversing lapatinib resistance of HER2-positive breast cancer cells. Our data provide clear, novel evidence of both anti-apoptotic and pro-apoptotic functions of autophagy in breast cancer during lapatinib treatment. PMID- 26369545 TI - Adult With Congenital Heart Disease in Developing Country: Scope, Challenges and Possible Solutions. AB - OPINION STATEMENT: Adults with congenital heart disease (CHD) are rapidly increasing in numbers in developed countries where facilities for interventions for CHD are available to infants and children. Over 90 % of children survive to adulthood in these countries. However, less than 50 % of children born in developing countries undergo any form of intervention due to nonavailability of paediatric cardiac centres. Prevalence of CHD in adults is estimated at 3000 per million population in developed countries. Such data is not available from developing countries, but prevalence is likely to be much lower due to early attrition. In these countries, adult population with CHD mostly consists of relatively milder forms of CHD with a very small proportion of post-operated patients. Specialized centres for care of adults with CHD are sparse or nonexistent in most developing countries, although the situation is changing for the better in some of these countries. Major challenges to care of adults with CHD include lack of trained persons, low levels of awareness about the disease and lack of government interest. Sustainable strategies which are practical in the local environment are required to deal with these challenges. An urgent need is to initiate training of cardiologists and other team members, required for optimal care of these patients. Special clinics for adults with CHD, run by the trained staff, can be incorporated into already operational cardiac centres. Formation of expert groups and patient support groups will help to formulate local guidelines and to pursue advocacy with the government. Maintenance of registries for adults with CHD is necessary to generate data on disease burden and to set research priorities. It is likely that care for adult CHD will be delivered in less than ideal settings considering the limited resources available. PMID- 26369544 TI - Role of insulin-like growth factor-binding proteins in the pathophysiology and tumorigenesis of gastroesophageal cancers. AB - The insulin family of proteins include insulin-like growth factor binding proteins (IGFBPs) that are classified into two groups based on their differential affinities to IGFs: IGF high-affinity binding proteins (IGFBP1-6) and IGF low affinity IGFBP-related proteins (IGFBP-rP1-10). IGFBPs interact with many proteins, including their canonical ligands insulin-like growth factor 1 (IGF-I) and IGF-II. Together with insulin-like growth factor 1 (IGF1) receptor (IGF1R), IGF2R, and ligands (IGF1 and IGF2), IGFBPs participate in a complex signaling axis called IGF-IGFR-IGFBP. Numerous studies have demonstrated that the IGF-IGFR IGFBP axis is relevant in gastrointestinal (GI) and other cancers. The presence of different IGFBPs have been reported in gastrointestinal cancers, including esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAD or EAC), and gastric adenocarcinoma (GAD or GAC). A literature-based survey clearly indicates that an urgent need exists for a focused review of the role of IGFBPs in gastrointestinal cancers. The aim of this review is to present the biochemical and molecular characteristics of IGFBPs with an emphasis specifically on the role of these proteins in the pathophysiology and tumorigenesis of gastroesophageal cancers. PMID- 26369546 TI - CD5 positivity is an independent adverse prognostic factor in elderly patients with diffuse large B cell lymphoma. AB - Diffuse large B cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma. Age over 60 years is one of the five parameters of the International Prognostic Index (IPI), which is the most important clinical prognostic predictor in DLBCL. A previous study on German DLBCL patients over 60 years of age showed that immunoblastic morphology, but not germinal center B cell-like (GCB)/non-GCB subtype, correlated with short survival. We collected 174 DLBCL cases over 60 years of age in Taiwan and performed immunophenotyping and detection of Epstein Barr virus (EBV)-encoded RNA (EBER) by in situ hybridization. Of the cases, 5.2 % were positive for CD5 and 5.7 % positive for EBER. Neither immunoblastic morphology nor GCB/non-GCB subtype correlated with survival. In univariate analysis, adverse prognostic factors included IPI >= 3 (P < 0.000001), B symptoms (P = 0.000075), bone marrow/peripheral blood involvement (P = 0.017), EBER positivity (P = 0.0013), and CD5 positivity (P = 0.016). In multivariate analysis, CD5 positivity was the only independent adverse prognostic factor (HR = 3.16; 95 % CI = 1.34-7.47; P = 0.0087) in addition to IPI >= 3 (HR = 3.07; 95 % CI = 1.84-5.11; P = 0.000018). Surprisingly, despite an overall 5.2 % incidence of central nervous system (CNS) relapse in our patients, none of the CD5+ cases experienced CNS relapse (P = 1.00). This is in stark contrast to the more frequent CNS relapse in Japanese CD5+ DLBCL patients. EBER positivity was associated with IPI >= 3 (P = 0.010), stage III-IV (P = 0.0082), and B symptoms (P = 0.011). In multivariate analysis, EBER positivity was not an independent adverse prognostic factor (P = 0.81), its effect being due likely to accompanying adverse clinical parameters. PMID- 26369547 TI - Old dilemma: asthma with irreversible airway obstruction or COPD. AB - Older asthmatic patients may develop fixed airway obstruction and clinical signs of chronic obstructive pulmonary disease (COPD). We investigated the added value of pathological evaluation of bronchial biopsies to help differentiate asthma from COPD, taking into account smoking, age, and inhaled corticosteroid (ICS) use. Asthma and COPD patients (24 of each category) were matched for ICS use, age, FEV(1), and smoking habits. Five pulmonary and five general pathologists examined bronchial biopsies using an interactive website, without knowing patient information. They were asked to diagnose asthma or COPD on biopsy findings in both a pairwise and randomly mixed order of cases during four different phases, with intervals of 4-6 weeks, covering a maximal period of 36 weeks. Clinically concordant diagnoses of asthma or COPD varied between 63 %-73 %, without important differences between pairwise vs randomly mixed examination or between general vs pulmonary pathologists. The highest percentage of concordant diagnoses was in young asthmatic patients without ICS use and in COPD patients with ICS use. In non ICS users with fixed airway obstruction, a COPD diagnosis was favored if abnormal presence of glands, squamous metaplasia, and submucosal infiltrate was present and an asthma diagnosis in case of abnormal presence of goblet cells. In ICS users with fixed airway obstruction, abnormal presence of submucosal infiltrates, basement membrane thickening, eosinophils, and glands was associated with asthma. Histological characteristics in bronchial biopsies are reproducibly recognized by pathologists, yet the differentiation by histopathology between asthma and COPD is difficult without information about ICS use. PMID- 26369549 TI - Illicit and injecting drug use among Indigenous young people in urban, regional and remote Australia. AB - INTRODUCTION AND AIMS: To examine patterns of illicit drug use among Australian Indigenous young people, identify correlates of frequent use separately in urban, regional and remote settings and characterise those who inject. DESIGN AND METHOD: Cross-sectional design at 40 Indigenous events. Self-complete surveys were administered to Indigenous people aged 16-29 years using mobile devices. RESULTS: 2,877 participants completed the survey. One in five reported using cannabis at least weekly in the previous year, but the use of other drugs was less prevalent. Patterns of drug use were largely similar across regions, although more participants in urban and regional areas reported using ecstasy (12% vs 11% vs 5%) and cocaine (6% vs 3% vs 1%) and more reported weekly cannabis use (18% vs 22% vs 14%). Injecting was rare (3%) but those who did inject reported a high incidence of needle sharing (37%). Methamphetamine (37%), heroin (36%) and methadone (26%) were the most commonly injected drugs, and injecting was related to prison experience (AOR 5.3 95% CI 2.8-10.0). DISCUSSION AND CONCLUSION: Attention is needed in relation to cannabis use, particularly among those Indigenous young people living in regional and urban settings. Also, although injecting is uncommon, it is associated with prison involvement. Priority must be given to reducing the numbers of Indigenous youth entering justice settings, delaying the age at first entry to justice settings, and reducing the risk of BBV acquisition while in custody through, for example, prison-based NSP, BBV education, and Indigenous-specific treatment that emphasises connection to country and culture. [Bryant J, Ward J, Wand H, Byron K, Bamblett A, Waples-Crowe P, Betts S, Coburn T, Delaney-Thiele D, Worth H, Kaldor J, Pitts M. Illicit and injecting drug use among Indigenous young people in urban, regional and remote Australia. Drug Alcohol Rev 2016;35:447-455]. PMID- 26369548 TI - Nighttime kidney transplantation is associated with less pure technical graft failure. AB - PURPOSE: To minimize cold ischemia time, transplantations with kidneys from deceased donors are frequently performed during the night. However, sleep deprivation of those who perform the transplantation may have adverse effects on cognitive and psychomotor performance and may cause reduced cognitive flexibility. We hypothesize that renal transplantations performed during the night are associated with an increased incidence of pure technical graft failure. METHODS: A retrospective analysis of data of the Dutch Organ Transplant Registry concerning all transplants from deceased donors between 2000 and 2013 was performed. Nighttime surgery was defined as the start of the procedure between 8 p.m. and 8 a.m. The primary outcome measure was technical graft failure, defined as graft loss within 10 days after surgery without signs of (hyper)acute rejection. RESULTS: Of 4.519 renal transplantations in adult recipients, 1.480 were performed during the night. The incidence of pure technical graft failure was 1.0 % for procedures started during the night versus 2.6 % for daytime surgery (p = .001). In a multivariable model, correcting for relevant donor, recipient and graft factors, daytime surgery was an independent predictor of pure technical graft failure (p < .001). CONCLUSIONS: Limitation of this study is mainly to its retrospective design, and the influence of some relevant variables, such as the experience level of the surgeon, could not be assessed. We conclude that nighttime surgery is associated with less pure technical graft failures. Further research is required to explore factors that may positively influence the performance of the surgical team during the night. PMID- 26369550 TI - Identifying and silencing tomato ripening genes with antisense genes. PMID- 26369551 TI - Improvement of antibiotic therapy and ICU survival in severe non-pneumococcal community-acquired pneumonia: a matched case-control study. AB - INTRODUCTION: We aimed to compare intensive care unit mortality due to non pneumococcal severe community-acquired pneumonia between the periods 2000-2002 and 2008-2014, and the impact of the improvement in antibiotic strategies on outcomes. METHODS: This was a matched case-control study enrolling 144 patients with non-pneumococcal severe pneumonia: 72 patients from the 2000-2002 database (CAPUCI I group) were paired with 72 from the 2008-2014 period (CAPUCI II group), matched by the following variables: microorganism, shock at admission, invasive mechanical ventilation, immunocompromise, chronic obstructive pulmonary disease, and age over 65 years. RESULTS: The most frequent microorganism was methicillin susceptible Staphylococcus aureus (22.1%) followed by Legionella pneumophila and Haemophilus influenzae (each 20.7%); prevalence of shock was 59.7%, while 73.6% of patients needed invasive mechanical ventilation. Intensive care unit mortality was significantly lower in the CAPUCI II group (34.7% versus 16.7%; odds ratio (OR) 0.78, 95% confidence interval (CI) 0.64-0.95; p = 0.02). Appropriate therapy according to microorganism was 91.5% in CAPUCI I and 92.7% in CAPUCI II, while combined therapy and early antibiotic treatment were significantly higher in CAPUCI II (76.4 versus 90.3% and 37.5 versus 63.9%; p < 0.05). In the multivariate analysis, combined antibiotic therapy (OR 0.23, 95% CI 0.07-0.74) and early antibiotic treatment (OR 0.07, 95% CI 0.02-0.22) were independently associated with decreased intensive care unit mortality. CONCLUSIONS: In non pneumococcal severe community-acquired pneumonia , early antibiotic administration and use of combined antibiotic therapy were both associated with increased intensive care unit survival during the study period. PMID- 26369552 TI - Alveolar soft part sarcoma of lung: report of a unique case with emphasis on diagnostic utility of molecular genetic analysis for TFE3 gene rearrangement and immunohistochemistry for TFE3 antigen expression. AB - Alveolar soft part sarcoma (ASPS) is a rare, malignant mesenchymal tumor of distinctive clinical, morphologic, ultrastructural, and cytogenetical characteristics. It typically arises in the extremities of adolescents and young adults, but has also been documented in a number of unusual sites, thus causing diagnostic confusions both clinically and morphologically. The molecular signature of ASPS is a specific der(17)t(X;17)(p11.2;q25) translocation, which results in the fusion of TFE3 transcription factor gene at Xp11.2 with ASPL at 17q25. Recent studies have shown that the ASPL-TFE3 fusion transcript can be identified by reverse-transcriptase polymerase chain reaction analysis and TFE3 gene rearragement can be detected using a dual-color, break apart fluorescence in situ hybridization assay in paraffin-embedded tissue, and the resultant fusion protein can be detected immunohistochemically with antibody directed to the carboxy terminal portion of TFE3. Herein, we report a unique case of ASPS presenting as an asymptomatic mass in the lung of a 48 year-old woman without evidence of a primary soft tissue tumor elsewhere at the time of initial diagnosis. To the best of our knowledge, this is the third report of such cases appearing in the English language literature to date. We emphasize the differential diagnoses engendered by ASPS including a series of tumors involving the lung that have nested and alveolar growth patterns, and both clear and eosinophilic cytoplasm, and demonstrate the utility of molecular genetic analysis for TFE3 rearrangement and immunohistochemistry for TFE3 antigen expression for arriving at accurate diagnosis. PMID- 26369553 TI - Alternative scenarios: harnessing mid-level providers and evidence-based practice in primary dental care in England through operational research. AB - BACKGROUND: In primary care dentistry, strategies to reconfigure the traditional boundaries of various dental professional groups by task sharing and role substitution have been encouraged in order to meet changing oral health needs. AIM: The aim of this research was to investigate the potential for skill mix use in primary dental care in England based on the undergraduate training experience in a primary care team training centre for dentists and mid-level dental providers. METHODS: An operational research model and four alternative scenarios to test the potential for skill mix use in primary care in England were developed, informed by the model of care at a primary dental care training centre in the south of England, professional policy including scope of practice and contemporary evidence-based preventative practice. The model was developed in Excel and drew on published national timings and salary costs. The scenarios included the following: "No Skill Mix", "Minimal Direct Access", "More Prevention" and "Maximum Delegation". The scenario outputs comprised clinical time, workforce numbers and salary costs required for state-funded primary dental care in England. RESULTS: The operational research model suggested that 73% of clinical time in England's state-funded primary dental care in 2011/12 was spent on tasks that may be delegated to dental care professionals (DCPs), and 45- to 54 year-old patients received the most clinical time overall. Using estimated National Health Service (NHS) clinical working patterns, the model suggested alternative NHS workforce numbers and salary costs to meet the dental demand based on each developed scenario. For scenario 1:"No Skill Mix", the dentist-only scenario, 81% of the dentists currently registered in England would be required to participate. In scenario 2: "Minimal Direct Access", where 70% of examinations were delegated and the primary care training centre delegation patterns for other treatments were practised, 40% of registered dentists and eight times the number of dental therapists currently registered would be required; this would save 38% of current salary costs cf. "No Skill Mix". Scenario 3: "More Prevention", that is, the current model with no direct access and increasing fluoride varnish from 13.1% to 50% and maintaining the same model of delegation as scenario 2 for other care, would require 57% of registered dentists and 4.7 times the number of dental therapists. It would achieve a 1% salary cost saving cf. "No Skill Mix". Scenario 4 "Maximum Delegation" where all care within dental therapists' jurisdiction is delegated at 100%, together with 50% of restorations and radiographs, suggested that only 30% of registered dentists would be required and 10 times the number of dental therapists registered; this scenario would achieve a 52% salary cost saving cf. "No Skill Mix". CONCLUSION: Alternative scenarios based on wider expressed treatment need in national primary dental care in England, changing regulations on the scope of practice and increased evidence-based preventive practice suggest that the majority of care in primary dental practice may be delegated to dental therapists, and there is potential time and salary cost saving if the majority of diagnostic tasks and prevention are delegated. However, this would require an increase in trained DCPs, including role enhancement, as part of rebalancing the dental workforce. PMID- 26369554 TI - Increased self-efficacy: the experience of high-intensity exercise of nursing home residents with dementia - a qualitative study. AB - BACKGROUND: There has been increasing interest in the use of non-pharmacological interventions, such as physical exercise, to improve the well-being of nursing home residents with dementia. For reasons regarding disease symptoms, persons with dementia might find it difficult to participate in exercise programs. Therefore, it is important to find ways to successfully promote regular exercise for patients in residential care. Several quantitative studies have established the positive effects of exercise on biopsychosocial factors, such as self efficacy in older people; however, little is known regarding the qualitative aspects of participating in an exercise program among older people with dementia. From the perspective of residents, we explored the experiences of participating in a high-intensity functional exercise program among nursing home residents with dementia. METHODS: The participants were eight elderly people with mild-to moderate dementia. We conducted semi-structured interviews one week after they had finished a 10-week supervised high-intensity exercise program. We analyzed the data using an inductive content analysis. RESULTS: Five overreaching and interrelated themes emerged from the interviews: "Pushing the limits," "Being invested in," "Relationships facilitate exercise participation," "Exercise revives the body, increases independence and improves self-esteem" and "Physical activity is a basic human necessity--use it or lose it!" The results were interpreted in light of Bandura's self-efficacy theory. The exercise program seemed to improve self-efficacy through several mechanisms. By being involved, "being invested in" and having something expected of them, the participants gained a sense of empowerment in their everyday lives. The importance of social influences related to the exercise instructor and the exercise group was accentuated by the participants. CONCLUSIONS: The nursing home residents had, for the most part, positive experiences with regard to participating in the exercise program. The program seemed to increase their self-efficacy through several mechanisms. The instructor competence emerged as an important facilitating factor. The participants emphasized the importance of physical activity in the nursing home. PMID- 26369555 TI - MRI characteristics of early PML-IRIS after natalizumab treatment in patients with MS. AB - OBJECTIVE: The early detection of MRI findings suggestive of immune reconstitution inflammatory syndrome (IRIS) in natalizumab-associated progressive multifocal leukoencephalopathy (PML) is of crucial clinical relevance in terms of treatment decision-making and clinical outcome. The aim of this study was to investigate the earliest imaging characteristics of PML-IRIS manifestation in natalizumab-treated patients with multiple sclerosis and describe an imaging pattern that might aid in the early and specific diagnosis. METHODS: This was a retrospective study assessing brain MRI of 26 patients with natalizumab associated PML presenting with lesions suggestive of PML-IRIS during follow-up. MRI findings were evaluated considering the imaging findings such as mass effect, swelling, contrast enhancement, new perivascular T2 lesions and signs suggestive of meningeal inflammation. RESULTS: Contrast enhancement was the most common imaging sign suggestive of PML-IRIS, seen in 92.3% of the patients (with patchy and/or punctuate pattern in 70.8% and 45.8% respectively), followed by new T2 lesions with a perivascular distribution pattern (34.6%). In those patients with contrast enhancement, the enhancement was present in the lesion periphery in 95.8% of the patients. Contrast-enhancing lesions with a perivascular distribution pattern outside of the PML lesion were observed in 33.3% of the patients. The most common overall pattern was contrast enhancement in the border of the PML lesion with either a patchy or punctuate appearance in 88.5% of all patients. CONCLUSIONS: Contrast enhancement is the most common earliest sign of natalizumab-associated PML-IRIS with a frequent imaging pattern of contrast enhancing lesions with either a patchy or punctuate appearance in the border of the PML lesion. PMID- 26369557 TI - Corbyn appoints new shadow health secretary. PMID- 26369556 TI - Avian pathogenic Escherichia coli (APEC) infection alters bone marrow transcriptome in chickens. AB - BACKGROUND: Avian pathogenic Escherichia coli (APEC) is a major cause of disease impacting animal health. The bone marrow is the reservoir of immature immune cells; however, it has not been examined to date for gene expression related to developmental changes (cell differentiation, maturation, programming) after APEC infection. Here, we study gene expression in the bone marrow between infected and non-infected animals, and between infected animals with mild (resistant) versus severe (susceptible) pathology, at two times post-infection. RESULTS: We sequenced 24 bone marrow RNA libraries generated from the six different treatment groups with four replicates each, and obtained an average of 22 million single end, 100-bp reads per library. Genes were detected as differentially expressed (DE) between APEC treatments (mild pathology, severe pathology, and mock challenged) at a given time point, or DE between 1 and 5 days post-infection (dpi) within the same treatment group. Results demonstrate that many immune cells, genes and related pathways are key contributors to the different responses to APEC infection between susceptible and resistant birds and between susceptible and non-challenged birds, at both times post-infection. In susceptible birds, lymphocyte differentiation, proliferation, and maturation were greatly impaired, while the innate and adaptive immune responses, including dendritic cells, monocytes and killer cell activity, TLR- and NOD-like receptor signaling, as well as T helper cells and many cytokine activities, were markedly enhanced. The resistant birds' immune system, however, was similar to that of non-challenged birds. CONCLUSION: The DE genes in the immune cells and identified signaling models are representative of activation and resolution of infection in susceptible birds at both post-infection days. These novel results characterizing transcriptomic response to APEC infection reveal that there is combinatorial activity of multiple genes controlling myeloid cells, and B and T cell lymphopoiesis, as well as immune responses occurring in the bone marrow in these early stages of response to infection. PMID- 26369559 TI - Wired to freedom: Life science, public politics, and the case of Cochlear Implantation. AB - Cochlear Implantation is now regarded as the most successful medical technology. It carries promises to provide deaf/hearing impaired individuals with a technological sense of hearing and an access to participate on a more equal level in social life. In this article, we explore the adoption of cochlear implantations among Danish users in order to shed more light on their social and political implications. We situate cochlear implantation in a framework of new life science advances, politics, and user experiences. Analytically, we draw upon the notion of social imaginary and explore the social dimension of life science through a notion of public politics adopted from the political theory of John Dewey. We show how cochlear implantation engages different social imaginaries on the collective and individual levels and we suggest that users share an imaginary of being "wired to freedom" that involves new access to social life, continuous communicative challenges, common practices, and experiences. In looking at their lives as "wired to freedom," we hope to promote a wider spectrum of civic participation in the benefit of future life science developments within and beyond the field of Cochlear Implantation. As our empirical observations are largely based in the Scandinavian countries (notably Denmark), we also provide some reflections on the character of the technology-friendly Scandinavian welfare states and the unintended consequences that may follow in the wake of rapid technology implementation of life science in society. PMID- 26369558 TI - Using proteomic analysis to investigate uniconazole-induced phytohormone variation and starch accumulation in duckweed (Landoltia punctata). AB - BACKGROUND: Duckweed (Landoltia punctata) has the potential to remediate wastewater and accumulate enormous amounts of starch for bioethanol production. Using systematical screening, we determined that the highest biomass and starch percentage of duckweed was obtained after uniconazole application. Uniconazole contributes to starch accumulation of duckweed, but the molecular mechanism is still unclear. RESULTS: To elucidate the mechanisms of high starch accumulation, in the study, the responses of L. punctata to uniconazole were investigated using a quantitative proteomic approach combined with physiological and biochemical analysis. A total of 3327 proteins were identified. Among these identified proteins, a large number of enzymes involved in endogenous hormone synthetic and starch metabolic pathways were affected. Notably, most of the enzymes involved in abscisic acid (ABA) biosynthesis showed up-regulated expression, which was consistent with the content variation. The increased endogenous ABA may up regulate expression of ADP-glucose pyrophosphorylase to promote starch biosynthesis. Importantly, the expression levels of several key enzymes in the starch biosynthetic pathway were up-regulated, which supported the enzymatic assay results and may explain why there is increased starch accumulation. CONCLUSIONS: These generated data linked uniconazole with changes in expression of enzymes involved in hormone biosynthesis and starch metabolic pathways and elucidated the effect of hormones on starch accumulation. Thus, this study not only provided insights into the molecular mechanisms of uniconazole-induced hormone variation and starch accumulation but also highlighted the potential for duckweed to be feedstock for biofuel as well as for sewage treatment. PMID- 26369560 TI - Large-scale transcriptional profiling of lignified tissues in Tectona grandis. AB - BACKGROUND: Currently, Tectona grandis is one of the most valuable trees in the world and no transcript dataset related to secondary xylem is available. Considering how important the secondary xylem and sapwood transition from young to mature trees is, little is known about the expression differences between those successional processes and which transcription factors could regulate lignin biosynthesis in this tropical tree. Although MYB transcription factors are one of the largest superfamilies in plants related to secondary metabolism, it has not yet been characterized in teak. These results will open new perspectives for studies of diversity, ecology, breeding and genomic programs aiming to understand deeply the biology of this species. RESULTS: We present a widely expressed gene catalog for T. grandis using Illumina technology and the de novo assembly. A total of 462,260 transcripts were obtained, with 1,502 and 931 genes differentially expressed for stem and branch secondary xylem, respectively, during age transition. Analysis of stem and branch secondary xylem indicates substantial similarity in gene ontologies including carbohydrate enzymes, response to stress, protein binding, and allowed us to find transcription factors and heat-shock proteins differentially expressed. TgMYB1 displays a MYB domain and a predicted coiled-coil (CC) domain, while TgMYB2, TgMYB3 and TgMYB4 showed R2R3-MYB domain and grouped with MYBs from several gymnosperms and flowering plants. TgMYB1, TgMYB4 and TgCES presented higher expression in mature secondary xylem, in contrast with TgMYB2, TgHsp1, TgHsp2, TgHsp3, and TgBi whose expression is higher in young lignified tissues. TgMYB3 is expressed at lower level in secondary xylem. CONCLUSIONS: Expression patterns of MYB transcription factors and heat-shock proteins in lignified tissues are dissimilar when tree development was evaluated, obtaining more expression of TgMYB1 and TgMYB4 in lignified tissues of 60-year-old trees, and more expression in TgHsp1, TgHsp2, TgHsp3 and TgBi in stem secondary xylem of 12-year-old trees. We are opening a door for further functional characterization by reverse genetics and marker-assisted selection with those genes. Investigation of some of the key regulators of lignin biosynthesis in teak, however, could be a valuable step towards understanding how rigidity of teak wood and extractives content are different from most other woods. The obtained transcriptome data represents new sequences of T. grandis deposited in public databases, representing an unprecedented opportunity to discover several related-genes associated with secondary xylem such as transcription factors and stress-related genes in a tropical tree. PMID- 26369561 TI - Scrub typhus mimicking Parkinson's disease. AB - BACKGROUND: Scrub typhus is a re-emerging infection in Sri Lanka. It often poses a diagnostic challenge and tends to present as a febrile illness of uncertain origin. Undiagnosed illness may progress to serious multi-systemic complications. Here we report a case of scrub typhus presenting with features of Parkinsonism. CASE PRESENTATION: A 62-year-old previously healthy Sri Lankan native male from the Western province of Sri Lanka presented with high fever with malaise, myalgia and arthralgia for 17 days. On the 5th day of illness he developed intermittent resting tremor in his right arm and leg associated with stiffness, difficulty in carrying out normal work and difficulty in smiling. He denied similar previous episodes. There were no other associated neurological manifestations. Clinical examination revealed a high amplitude low frequency resting tremor in his right hand, a mask-like face and increased muscle tone limited to the right side with normal reflexes. The rest of the system examination was normal except for an eschar over the abdomen. His investigations revealed lymphocytic leukocytosis, high erythrocyte sedimentation rate and immunofluorescence assay-IgM and IgG against Orientia tsutsugamushi Karp antigen were positive with rising titers. With oral doxycycline and azithromycin his fever settled within 48 h and a complete recovery of Parkinson's features was observed within 2 weeks. CONCLUSION: Doctors practicing in endemic regions should be familiar with delayed clinical manifestations of scrub typhus and should carefully look for an eschar in order to avoid delay in the diagnosis. PMID- 26369562 TI - Equity of access under Korean national long-term care insurance: implications for long-term care reform. AB - BACKGROUND: The national long-term care insurance was implemented in July 2008. Few studies have been conducted with representative national survey data since the long-term care insurance was introduced. Therefore, this study examines the extent to which equity in the use of long-term care has been achieved in Korea. METHODS: The Aday-Andersen model was used as a conceptual model, based on the Korean Health Panel Study which was conducted in 2011. Descriptive and logistic regression analysis was performed to examine the relationship between the dependent and independent variables and the relative importance of factors as predictors of utilization. RESULTS: The results of this study indicated that those who rated his or her health to be fair, good, and very good, had no limited activities, were disabled, and had insurance coverage were more likely to use long-term care services, respectively. Their decision to use long-term care was primarily affected by need (health status, limited activity, disability) and enabling (insurance coverage) factors. The findings also indicated that the introduction of a national long-term care insurance program did not yield a fully equitable distribution of services. CONCLUSIONS: Long-term care reforms in Korea should continue to concentrate on expanding insurance coverage and reducing the inequities reflected in disparities in consumer cost-sharing and associated patterns of utilization across plans. The subsequent impact on managed care and expenditures need to be more fully understood. PMID- 26369563 TI - The Tiotropium Safety and Performance in Respimat(r) (TIOSPIR(r)) Trial: Spirometry Outcomes. AB - BACKGROUND: Tiotropium Safety and Performance in Respimat(r) (TIOSPIR(r)) compared the safety and efficacy of tiotropium Respimat(r) and tiotropium HandiHaler(r) in patients with chronic obstructive pulmonary disease (COPD). A prespecified spirometry substudy compared the lung function efficacy between treatment groups. METHODS: TIOSPIR(r) was a large-scale, long-term (2.3-year), event-driven, randomized, double-blind, parallel-group trial of 17,135 patients with COPD. In the spirometry substudy, trough forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were measured at baseline and every 24 weeks for the duration of the trial. RESULTS: The substudy included 1370 patients who received once-daily tiotropium Respimat(r) 5 MUg (n = 461), 2.5 MUg (n = 464), or tiotropium HandiHaler(r) 18 MUg (n = 445). Adjusted mean trough FEV1 (average 24-120 weeks) was 1.285, 1.258, and 1.295 L in the Respimat(r) 5 MUg, 2.5 MUg, and HandiHaler(r) 18 MUg groups (difference versus HandiHaler(r) [95 % CI]: -10 [-38, 18] mL for Respimat(r) 5 MUg and, -37 [-65, -9] mL for Respimat(r) 2.5 MUg); achieving noninferiority to tiotropium HandiHaler(r) 18 MUg for tiotropium Respimat(r) 5 but not for 2.5 MUg (prespecified analysis). Adjusted mean trough FVC was 2.590, 2.544, and 2.593 L in the Respimat(r) 5 MUg, 2.5 MUg, and HandiHaler(r) 18 MUg groups. The rates of FEV1 decline over 24 to 120 weeks were similar for the three treatment arms (26, 40, and 34 mL/year for the tiotropium Respimat(r) 5-MUg, 2.5-MUg, and HandiHaler(r) 18-MUg groups). The rate of FEV1 decline in GOLD I + II patients was greater than in GOLD III + IV patients (46 vs. 23 mL/year); as well as in current versus ex-smokers, in patients receiving combination therapies at baseline versus not, and in those experiencing an exacerbation during the study versus not. CONCLUSIONS: The TIOSPIR(r) spirometry substudy showed that tiotropium Respimat(r) 5 MUg was noninferior to tiotropium HandiHaler(r) 18 MUg for trough FEV1, but Respimat(r) 2.5 MUg was not. Tiotropium Respimat(r) 5 MUg provides similar bronchodilator efficacy to tiotropium HandiHaler(r) 18 MUg with comparable rates of FEV1 decline. The rate of FEV1 decline varied based on disease severity, with a steeper rate of decline observed in patients with moderate airway obstruction. TRIAL REGISTRATION: NCT01126437. PMID- 26369564 TI - Dietary overlap and seasonality in three species of mormoopid bats from a tropical dry forest. AB - Competing hypotheses explaining species' use of resources have been advanced. Resource limitations in habitat and/or food are factors that affect assemblages of species. These limitations could drive the evolution of morphological and/or behavioural specialization, permitting the coexistence of closely related species through resource partitioning and niche differentiation. Alternatively, when resources are unlimited, fluctuations in resources availability will cause concomitant shifts in resource use regardless of species identity. Here, we used next-generation sequencing to test these hypotheses and characterize the diversity, overlap and seasonal variation in the diet of three species of insectivorous bats of the genus Pteronotus. We identified 465 prey (MOTUs) in the guano of 192 individuals. Lepidoptera and Diptera represented the most consumed insect orders. Diet of bats exhibited a moderate level of overlap, with the highest value between Pteronotus parnellii and Pteronotus personatus in the wet season. We found higher dietary overlap between species during the same seasons than within any single species across seasons. This suggests that diets of the three species are driven more by prey availability than by any particular predator-specific characteristic. P. davyi and P. personatus increased their dietary breadth during the dry season, whereas P. parnellii diet was broader and had the highest effective number of prey species in all seasons. This supports the existence of dietary flexibility in generalist bats and dietary niche overlapping among groups of closely related species in highly seasonal ecosystems. Moreover, the abundance and availability of insect prey may drive the diet of insectivores. PMID- 26369566 TI - Mitochondrial genetic variations in natural house fly (Musca domestica L.) populations from the western and southern parts of Turkey. AB - The house fly Musca domestica Linnaeus (Diptera) is one of the most studied species that is globally distributed and well known to everyone. In order to ensure baseline knowledge for the genetic resources of the species, genetic variation in M. domestica populations from western and southern parts of Turkey was investigated using nucleotide sequence analysis of 348 base pairs (bp) in the mitochondrial cytochrome oxidase subunit I gene (COI). Samples of 192 individuals were collected from 16 localities of Turkey. There were 10 variable sites defining two haplotypes of COI in this species. There was no difference in geographical distribution frequency between the two regions of Turkey. Overall, haplotype diversity (h) was low, ranging from 0 to 0.5606 with the average overall value of 0.178 +/- 0.04 and nucleotide diversity (pi), ranged from 0 to 0.0056 with the overall mean of 0.0016. Analysis of molecular variance (AMOVA) indicated that genetic differentiation within individuals and populations was low and significant (p < 0.05). Except Afyon population, conventional population statistic FST showed no significant genetic structure along the range of M. domestica populations. Sixteen populations clustered under six haplotypes and two of them are unique to Turkey. Haplotype networks suggested that house fly populations in Turkey are grouped with the Palearctic region, which is the most probable place for the origin of this species. PMID- 26369567 TI - Response to Letter-to-the-editor. PMID- 26369565 TI - Stem cell-derived exosomes: roles in stromal remodeling, tumor progression, and cancer immunotherapy. AB - Stem cells are known to maintain stemness at least in part through secreted factors that promote stem-like phenotypes in resident cells. Accumulating evidence has clarified that stem cells release nano-vesicles, known as exosomes, which may serve as mediators of cell-to-cell communication and may potentially transmit stem cell phenotypes to recipient cells, facilitating stem cell maintenance, differentiation, self-renewal, and repair. It has become apparent that stem cell-derived exosomes mediate interactions among stromal elements, promote genetic instability in recipient cells, and induce malignant transformation. This review will therefore discuss the potential of stem cell derived exosomes in the context of stromal remodeling and their ability to generate cancer-initiating cells in a tumor niche by inducing morphologic and functional differentiation of fibroblasts into tumor-initiating fibroblasts. In addition, the immunosuppressive potential of stem cell-derived exosomes in cancer immunotherapy and their prospective applications in cell-free therapies in future translational medicine is discussed. PMID- 26369568 TI - Erratum to: Impact of opportunistic testing in a systematic cervical cancer screening program: a nationwide registry study. PMID- 26369569 TI - Comparative Toxicity of Tapentadol and Tramadol Utilizing Data Reported to the National Poison Data System. AB - BACKGROUND: Tapentadol (TAP) and tramadol (TRA) provide pain relief through similar monoaminergic and opioid agonist properties. OBJECTIVE: To compare clinical effects and medical outcomes between TAP and TRA exposures reported to the National Poison Data System of the American Association of Poison Control Centers. METHODS: A retrospective cohort study was conducted analyzing national data for single medication TAP or TRA cases reported from June 2009 through December 2011. Case outcomes, dichotomized as severe versus mild; clinical effects; and use of naloxone were compared. RESULTS: There were 217 TAP and 8566 TRA cases. Significantly more severe outcomes were associated with TAP exposures for an all-age comparison (relative risk [RR] = 1.24; 95% CI = 1.04-1.48), and for the <6-year-old age group (RR = 5.76; 95% CI = 2.20-15.11). Patients with TAP exposures had significantly greater risk of respiratory depression (RR = 5.56; 95% CI = 3.50-8.81), coma (RR = 4.16; 95% CI = 2.33-7.42), drowsiness/lethargy (RR = 1.38; 95% CI = 1.15-1.66), slurred speech (RR = 3.51; 95% CI = 1.98-6.23), hallucination/delusion (RR = 7.25; 95% CI = 3.61-14.57), confusion (RR = 2.54; 95% CI = 1.56-4.13) and use of naloxone (RR = 3.80; 95% CI = 2.96-4.88). TRA exposures had significantly greater risk of seizures (RR = 7.94; 95% CI = 2.99 20.91) and vomiting (RR = 1.96; 95% CI = 1.07-3.60). CONCLUSION: TAP was associated with significantly more toxic clinical effects and severe outcomes consistent with an opioid agonist. TRA was associated with significantly higher rates of seizures and vomiting. PMID- 26369571 TI - Hydration status measured by BCM: A potential modifiable risk factor for peritonitis in patients on peritoneal dialysis. AB - AIM: Peritoneal dialysis peritonitis and fluid overhydration (OH) are frequent problems in peritoneal dialysis. The latter can cause gut wall oedema or be associated with malnutrition. Both may lead to increased peritonitis risk. We wished to determine if OH is an independent risk factor for peritonitis (caused by enteric organisms). METHODS: Retrospectively study of patients with >2 bioimpedance assessments (Body Composition Monitor). We compared peritonitis rates of patients with above or below the median time-averaged hydration parameter (OH/extracellular water, OH/ECW). Multivariate analysis was performed to determine independent risk factors for peritonitis by enteric organism. RESULTS: We studied 580 patients. Peritonitis was experienced by 28% patients (followed up for an average of 17 months). The overall peritonitis rate was 1:34 patient months. Patients with low OH/ECW values had significantly lower rates of peritonitis from enteric organisms than overhydrated patients (incident rate ratio 1.53, 95% confidence interval 1.38-1.70, P < 0.001). Hydration remained an independent predictor of peritonitis from enteric organisms when multivariate model included demographic parameters (odds ratio for a 1% increment of OH/ECW was 1.05; 95% confidence interval 1.01-1.10, P < 0.02). However, including biochemical parameters of malnutrition reduced the predictive power of overhydration. CONCLUSION: We found an association between overhydration and increased rates of peritonitis. While this may partly be due to the high co morbidity of patients (advanced age and diabetes), on multivariate analysis, only inclusion of nutritional parameters reduced this association. It remains to be determined if overhydration will prove to be a modifiable risk factor for peritonitis or whether malnutrition will prove to be more important. PMID- 26369570 TI - Brain Injury and Development in Preterm Infants Exposed to Fentanyl. AB - BACKGROUND: Fentanyl is commonly used in preterm infants. Relatively little is known regarding the neurodevelopmental outcomes of preterm infants exposed to fentanyl. OBJECTIVE: To investigate the association between cumulative fentanyl dose and brain injury and diameters in a cohort of preterm infants. METHODS: Data on demographics, perinatal course, and neonatal course, including total fentanyl exposure prior to term equivalent age, were retrospectively evaluated for 103 infants born at <=30 weeks gestational age (mean gestational age 26.9 +/- 1.8 weeks) who underwent magnetic resonance imaging at term equivalent age. Magnetic resonance images were evaluated for brain injury and regional brain diameters. Developmental testing was conducted at term equivalent and 2 years of age. RESULTS: Seventy-eight infants (76%) received fentanyl (median cumulative dose 3 ug/kg, interquartile range 1-441 ug/kg). Cumulative fentanyl dose in the first week of life correlated with the incidence of cerebellar hemorrhage after correction for covariates (odds ratio 2.1, 95% confidence interval 1.1-4.1). Cumulative fentanyl dose before term equivalent age correlated with reductions in transverse cerebellar diameter after correction for covariates, including the presence of cerebellar hemorrhage (r = 0.461, P = 0.002). No correlation was detected between cumulative fentanyl dose and development at 2 years of age. CONCLUSIONS: Higher cumulative fentanyl dose in preterm infants correlated with a higher incidence of cerebellar injury and lower cerebellar diameter at term equivalent age. Our findings must be taken with caution, but emphasize the need for future prospective trials examining the risks and benefits of commonly used analgesic agents in preterm infants. PMID- 26369572 TI - Determination of magnetic anisotropy constants and domain wall pinning energy of Fe/MgO(001) ultrathin film by anisotropic magnetoresistance. AB - It is challenging to determine domain wall pinning energy and magnetic anisotropy since both coherent rotation and domain wall displacement coexist during magnetization switching process. Here, angular dependence anisotropic magnetoresistance (AMR) measurements at different magnetic fields were employed to determine magnetic anisotropy constants and domain wall pinning energy of Fe/MgO(001) ultrathin film. The AMR curves at magnetic fields which are high enough to ensure the coherent rotation of magnetization indicate a smooth behavior without hysteresis between clockwise (CW) and counter-clockwise (CCW) rotations. By analyzing magnetic torque, the magnetic anisotropy constants can be obtained. On the other hand, the AMR curves at low fields show abrupt transitions with hysteresis between CW and CCW rotations, suggesting the presence of multi domain structures. The domain wall pinning energy can be obtained by analyzing different behaviors of AMR. Our work suggests that AMR measurements can be employed to figure out precisely the contributions of magnetic anisotropy and domain wall pinning energy, which is still a critical issue for spintronics. PMID- 26369573 TI - iCONVERT: an integrated device for the UV-assisted determination of H2S via mid infrared gas sensors. AB - In this technical note, we describe an integrated device platform for performing in-flow gaseous conversion reactions based on ultraviolet (UV) irradiation. The system combines, using the same footprint, an integrated UV-conversion device (iCONVERT), a preconcentrator unit (iPRECON), and a new generation of mid infrared (MIR) gas cell simultaneously serving as a photon conduit, i.e., so called substrate-integrated hollow waveguide (iHWG) optically coupled to a compact Fourier transform-infrared (FT-IR) spectrometer. The iCONVERT is assembled from two blocks of aluminum (dimensions, 75 mm * 50 mm * 40 mm; L * W * D) containing 4 miniaturized UV-lamps (47mm * 6 mm * 47 mm each). For the present study, the iPRECON-iCONVERT-iHWG sensing platform has specifically been tailored to the determination of H2S in gaseous samples. Thereby, the quantitative UV assisted conversion of the rather weak IR-absorber H2S into the more pronouncedly responding SO2 is used for hydrogen sulfide detection. A linear calibration model was established in the range of 7.5 to 100 ppmv achieving a limit of detection at 1.5 ppmv using 10 min of sample preconcentration (onto Molecular Sieve 5A) at a flow rate of 200 mL min(-1). When compared to a conventional UV-conversion system, the iCONVERT revealed similar performance. Considering the potential for system miniaturization using, e.g., dedicated quantum cascade lasers (QCL) in lieu of the FT-IR spectrometer, the developed sensing platform may be further evolved into a hand-held device. PMID- 26369574 TI - What is a normal blood glucose? AB - Glucose is the key metabolic substrate for tissue energy production. In the perinatal period the mother supplies glucose to the fetus and for most of the gestational period the normal lower limit of fetal glucose concentration is around 3 mmol/L. Just after birth, for the first few hours of life in a normal term neonate appropriate for gestational age, blood glucose levels can range between 1.4 mmol/L and 6.2 mmol/L but by about 72 h of age fasting blood glucose levels reach normal infant, child and adult values (3.5-5.5 mmol/L). Normal blood glucose levels are maintained within this narrow range by factors which control glucose production and glucose utilisation. The key hormones which regulate glucose homoeostasis include insulin, glucagon, epinephrine, norepinephrine, cortisol and growth hormone. Pathological states that affect either glucose production or utilisation will lead to hypoglycaemia. Although hypoglycaemia is a common biochemical finding in children (especially in the newborn) it is not possible to define by a single (or a range of) blood glucose value/s. It can be defined as the concentration of glucose in the blood or plasma at which the individual demonstrates a unique response to the abnormal milieu caused by the inadequate delivery of glucose to a target organ (eg, the brain). Hypoglycaemia should therefore be considered as a continuum and the blood glucose level should be interpreted within the clinical scenario and with respect to the counter regulatory hormonal responses and intermediate metabolites. PMID- 26369575 TI - Influence of past breast feeding on pattern and severity of presentation of juvenile idiopathic arthritis. AB - This analysis aimed to study the influence of breast feeding on the pattern and severity of juvenile idiopathic arthritis (JIA) at presentation. The association between ever versus never breast feeding and disease severity at onset was compared in 923 children with JIA recruited to the UK Childhood Arthritis Prospective Study at first presentation to rheumatology. Fifty six per cent of children were ever breast fed (median 3.7 months). Breastfed children reported a lower median age at onset, a lower Childhood Health Assessment Questionnaire (CHAQ), a measure of disease severity, lower parent general evaluation scores and lower pain at presentation. There was a trend towards a higher proportion of breastfed children with rheumatoid factor-negative polyarthritis, but lesser enthesitis-related and psoriatic arthritis. There was a statistically significant inverse association between breast feeding and high CHAQ, even after adjusting for differences in socioeconomic status (adjusted OR 0.61 (95% CI 0.39 to 0.95)). Further work to understand the reasons behind these associations is required. PMID- 26369576 TI - Children's palliative care in low- and middle-income countries. AB - One-third of the global population is aged under 20 years. For children with life limiting conditions, palliative care services are required. However, despite 80% of global need occurring in low- and middle-income countries (LMICs), the majority of children's palliative care (CPC) is provided in high-income countries. This paper reviews the status of CPC services in LMICs--highlighting examples of best practice among service models in Malawi, Indonesia and Belarus- before reviewing the status of the extant research in this field. It concludes that while much has been achieved in palliative care for adults, less attention has been devoted to the education, clinical practice, funding and research needed to ensure children and young people receive the palliative care they need. PMID- 26369577 TI - Chronic lymphocytic thyroiditis is associated with invasive characteristics of differentiated thyroid carcinoma in children and adolescents. AB - BACKGROUND: The association between chronic lymphocytic thyroiditis (CLT) and thyroid cancer is an interesting topic. The aim of the present study was to evaluate if demographic and histological characteristics as well as the long-term outcome of thyroid cancer was different in children and adolescents with and without CLT. METHODS: The medical records of children and adolescents (<=21 years old) were reviewed. The following data were recorded: gender, year and age at diagnosis, family history of thyroid cancer, history of external radiation therapy, histological type (papillary and variants, follicular and variants), tumour size, multifocality, infiltration of thyroid parenchyma or surrounding soft tissues, vascular invasion, presence of lymph node and distant metastases. Information about the presence of TgAb and TPOAb was also collected. RESULTS: One hundred eight children and adolescents (median age 19.0, interquartile range 4.0 years) were diagnosed with differentiated thyroid carcinoma (DTC); 31 patients (28.7%) presented histological characteristics compatible with CLT. Infiltration of thyroid parenchyma was more frequent in patients with CLT compared to patients without (74.2% vs 48.1% respectively, P=0.024). Familial papillary thyroid carcinoma (PTC) was more frequent in patients with CLT compared to those without CLT (20.7% vs 2.8% respectively, P=0.009). There was no better outcome with respect to the presence of CLT or not. CONCLUSIONS: Children and adolescents with CLT present more frequently familial PTC as well as thyroid cancer with invasive characteristics. PMID- 26369578 TI - Ultrasensitive estrogen levels at 7 years of age predict earlier thelarche: evidence from girls of the growth and obesity Chilean cohort. AB - OBJECTIVE: Prepubertal estradiol equivalents have been inconsistently linked to age at thelarche; elucidating this relationship becomes relevant given the worldwide decline in the age of puberty onset. Thus, our aim is to assess whether prepubertal girls with higher serum levels of estradiol equivalents at age 7 have a greater risk of presenting early thelarche (ET). DESIGN: Nested case-control study within the Growth and Obesity Cohort Study of 1196 low-middle income children (~50% girls) from Santiago, Chile. Girls were defined as cases (ET; n=61) if breast bud appeared prior to 8 years of age; controls (n=91) had thelarche >8 years. METHODS: At 6.7 years, weight, height and waist circumference were measured and a fasting blood sample was obtained for measuring estrogen equivalent (ultrasensitive recombinant cell bioassay), DHEAS, leptin, insulin and IGF1. Beginning at 7 years old, Tanner staging was assessed prospectively twice a year and the appearance of breast bud was assessed by palpation. RESULTS: Mean serum estradiol-equivalent at 6.7 years was 3.9+/-3.6 pg/ml for cases and 3.6+/ 2.3 pg/ml for controls. Girls with ET had a higher risk of presenting elevated estradiol-equivalent (>=5 pg/ml) at 7 years (OR=2.05, 95% CI: 0.96-4.36) than controls that was borderline significant. However, after adjusting by BMI, insulin and IGF1 at age 7, the association between estradiol-equivalent and ET was significant (OR=2.29 (95% CI: 1.05-5.01)). CONCLUSIONS: Chilean girls from low to middle socioeconomic status with ET exhibited double the risk of having high levels of estradiol-equivalent at 7 years than girls with a later age of thelarche. Whole-body adiposity and increased adrenal activity did not explain the observed prepubertal estrogen increase. PMID- 26369579 TI - Proposal of a clinical response score and predictors of clinical response to 2 years of GH replacement therapy in adult GH deficiency. AB - OBJECTIVE: There is no single clinical marker to reliably assess the clinical response to growth hormone replacement therapy (GHRT) in adults with growth hormone deficiency (GHD). The objective of this study was to propose a clinical response score to GHRT in adult GHD and to establish clinical factors that predict clinical response. DESIGN: This was a prospective observational cohort study from the international KIMS database (Pfizer International Metabolic Database). METHODS: We included 3612 adult patients with GHD for proposing the response score and 844 patients for assessing predictors of response. We propose a clinical response score based on changes in total cholesterol, waist circumference and QoL-AGHDA quality of life measurements after 2 years of GHRT. A score point was added for each quintile of change in each variable, resulting in a sum score ranging from 3 to 15. For clinical response at 2 years, we analysed predictors at baseline and after 6 months using logistic regression analyses. RESULTS: In a baseline prediction model, IGF1, QoL-AGHDA, total cholesterol and waist circumference predicted response, with worse baseline parameters being associated with a favourable response (AUC 0.736). In a combined baseline and 6 month prediction model, baseline QoL-AGHDA, total cholesterol and waist circumference, and 6-month change in waist circumference were significant predictors of response (AUC 0.815). CONCLUSIONS: A simple clinical response score might be helpful in evaluating the success of GHRT. The baseline prediction model may aid in the decision to initiate GHRT and the combined prediction model may be helpful in the decision to continue GHRT. PMID- 26369580 TI - GtrA Protein Rv3789 Is Required for Arabinosylation of Arabinogalactan in Mycobacterium tuberculosis. AB - Mycobacterium tuberculosis possesses a thick and highly hydrophobic cell wall principally composed of a mycolyl-arabinogalactan-peptidoglycan complex, which is critical for survival and virulence. DprE1 is a well-characterized component of decaprenyl-phospho-ribose epimerase, which produces decaprenyl-phospho-arabinose (DPA) for the biosynthesis of mycobacterial arabinans. Upstream of dprE1 lies rv3789, which encodes a short transmembrane protein of the GtrA family, whose members are often involved in the synthesis of cell surface polysaccharides. We demonstrate that rv3789 and dprE1 are cotranscribed from a common transcription start site situated 64 bp upstream of rv3789. Topology mapping revealed four transmembrane domains in Rv3789 and a cytoplasmic C terminus consistent with structural models built using analysis of sequence coevolution. To investigate its role, we generated an unmarked rv3789 deletion mutant in M. tuberculosis. The mutant was characterized by impaired growth and abnormal cell morphology, since the cells were shorter and more swollen than wild-type cells. This phenotype likely stems from the decreased incorporation of arabinan into arabinogalactan and was accompanied by an accumulation of DPA. A role for Rv3789 in arabinan biosynthesis was further supported by its interaction with the priming arabinosyltransferase AftA, as demonstrated by a two-hybrid approach. Taken together, the data suggest that Rv3789 does not act as a DPA flippase but, rather, recruits AftA for arabinogalactan biosynthesis. IMPORTANCE: Upstream of the essential dprE1 gene, encoding a key enzyme of the decaprenyl phospho arabinose (DPA) pathway, lies rv3789, coding for a short transmembrane protein of unknown function. In this study, we demonstrated that rv3789 and dprE1 are cotranscribed from a common transcription start site located 64 bp upstream of rv3789 in M. tuberculosis. Furthermore, the deletion of rv3789 led to a reduction in arabinan content and to an accumulation of DPA, confirming that Rv3789 plays a role in arabinan biosynthesis. Topology mapping, structural modeling, and protein interaction studies suggest that Rv3789 acts as an anchor protein recruiting AftA, the first arabinosyl transferase. This investigation provides deeper insight into the mechanism of arabinan biosynthesis in mycobacteria. PMID- 26369582 TI - Death by Cystine: an Adverse Emergent Property from a Beneficial Series of Reactions. AB - In this issue of the Journal of Bacteriology, Chonoles Imlay et al. (K. R. Chonoles Imlay, S. Korshunov, and J. A. Imlay, J Bacteriol 197:3629-3644, 2015, http://dx.doi.org/10.1128/JB.00277-15) show that oxidative stress kills sulfur restricted Escherichia coli grown with sublethal H2O2 when challenged with cystine. Killing requires rapid and seemingly unregulated cystine transport and equally rapid cystine reduction to cysteine. Cysteine export completes an energy depleting futile cycle. Each reaction of the cycle could be beneficial. Together, a cystine-mediated vulnerability emerges during the transition from a sulfur restricted to a sulfur-replete environment, perhaps because of complexities of sulfur metabolism. PMID- 26369581 TI - Two-Component Signal Transduction Systems That Regulate the Temporal and Spatial Expression of Myxococcus xanthus Sporulation Genes. AB - When starved for nutrients, Myxococcus xanthus produces a biofilm that contains a mat of rod-shaped cells, known as peripheral rods, and aerial structures called fruiting bodies, which house thousands of dormant and stress-resistant spherical spores. Because rod-shaped cells differentiate into spherical, stress-resistant spores and spore differentiation occurs only in nascent fruiting bodies, many genes and multiple levels of regulation are required. Over the past 2 decades, many regulators of the temporal and spatial expression of M. xanthus sporulation genes have been uncovered. Of these sporulation gene regulators, two-component signal transduction circuits, which typically contain a histidine kinase sensor protein and a transcriptional regulator known as response regulator, are among the best characterized. In this review, we discuss prototypical two-component systems (Nla6S/Nla6 and Nla28S/Nla28) that regulate an early, preaggregation phase of sporulation gene expression during fruiting body development. We also discuss orphan response regulators (ActB and FruA) that regulate a later phase of sporulation gene expression, which begins during the aggregation stage of fruiting body development. In addition, we summarize the research on a complex two-component system (Esp) that is important for the spatial regulation of sporulation. PMID- 26369584 TI - New guidelines--new hope? PMID- 26369583 TI - Real-time and label-free analysis of binding thermodynamics of carbohydrate protein interactions on unfixed cancer cell surfaces using a QCM biosensor. AB - A novel approach to the study of binding thermodynamics and kinetics of carbohydrate-protein interactions on unfixed cancer cell surfaces using a quartz crystal microbalance (QCM) biosensor was developed, in which binding events take place at the cell surface, more closely mimicking a biologically relevant environment. In this study, colon adenocarcinoma cells (KM-12) and ovary adenocarcinoma cells (SKOV-3) grew on the optimized polystyrene-coated biosensor chip without fixation. The association and dissociation between the cell surface carbohydrates and a range of lectins, including WGA, Con A, UEA-I, GS-II, PNA and SBA, were monitored in real time and without label for evaluation of cell surface glycosylation. Furthermore, the thermodynamic and kinetic parameters of the interaction between lectins and cell surface glycan were studied, providing detailed information about the interactions, such as the association rate constant, dissociation rate constant, affinity constant, as well as the changes of entropy, enthalpy and Gibbs free energy. This application provides an insight into the cell surface glycosylation and the complex molecular recognition on the intact cell surface, which may have impacts on disease diagnosis and drug discovery. PMID- 26369586 TI - Supramolecular One-Dimensional n/p-Nanofibers. AB - Currently, there is a broad interest in the control over creating ordered electroactive nanostructures, in which electron donors and acceptors are organized at similar length scales. In this article, a simple and efficient procedure is reported en-route towards the construction of 1D arrays of crystalline pristine C60 and phenyl-C61-butyric acid methyl ester (PCBM) coated onto supramolecular fibers based on exTTF-pentapeptides. The resulting n/p nanohybrids have been fully characterized by a variety of spectroscopic (FTIR, UV Vis, circular dichroism, Raman and transient absorption), microscopic (AFM, TEM, and SEM), and powder diffraction (X-ray) techniques. Our experimental findings document the tendency of electroactive exTTF-fibers to induce the crystallization of C60 and PCBM, on one hand, and to afford 1D n/p-nanohybrids, on the other hand. Furthermore, photogenerated radical ion pairs, formed upon visible light irradiation of the n/p-nanohybrids, feature lifetimes on the range of 0.9-1.2 ns. PMID- 26369587 TI - Oxidative stress and damage to erythrocytes in patients with chronic obstructive pulmonary disease--changes in ATPase and acetylcholinesterase activity. AB - The study indicates, for the first time, the changes in both ATPase and AChE activities in the membrane of red blood cells of patients diagnosed with COPD. Chronic obstructive pulmonary disease (COPD) is one of the most common and severe lung disorders. We examined the impact of COPD on redox balance and properties of the membrane of red blood cells. The study involved 30 patients with COPD and 18 healthy subjects. An increase in lipid peroxidation products and a decrease in the content of -SH groups in the membrane of red blood cells in patients with COPD were observed. Moreover, an increase in the activity of glutathione peroxidase and a decrease in superoxide dismutase, but not in catalase activity, were found as well. Significant changes in activities of erythrocyte membrane enzymes in COPD patients were also evident demonstrated by a considerably lowered ATPase activity and elevated AChE activity. Changes in the structure and function of red blood cells observed in COPD patients, together with changes in the activity of the key membrane enzymes (ATPases and AChE), can result from the imbalance of redox status of these cells due to extensive oxidative stress induced by COPD disease. PMID- 26369588 TI - Opioid Prescribing Laws and Emergency Department Guidelines for Chronic Non Cancer Pain in Washington State. AB - Rising mortality rates, increased opioid prescription abuse, and a perceived need to provide practitioners with structured guidance in opioid prescribing have prompted the Washington State Legislature to establish new legal standards of practice regarding chronic non-cancer pain management. Clinicians are required to conduct a detailed physical examination and health history prior to treatment. Risk assessments for abuse and detailed periodic reviews of treatment are required at least every 6 months. Those considered "high risk" or who have significant psychiatric comorbidities will be required to sign and follow a written agreement or pain contract, obtain their pain prescriptions from a single provider, and submit to biological drug screening. Unless an exemption exists, patients prescribed > 120 mg of morphine-equivalents daily, considered severe pain nonresponders, necessitating dosage escalation, diagnosed with multifaceted mental health-related comorbidities, demonstrating diagnostic ambiguity, and/or requiring significant treatment individualization are referred to a pain specialist. Episodic care settings should refrain from supplying opioids to chronic pain patients whenever possible. The ER is for Emergencies coalition instituted the Seven Best Practices program throughout the state to reduce unnecessary visits, coordinate prescribing practice, reduce Medicaid expenditures, and improve overall patient care. The state reported approximately $33.65 million in savings in 2013 through the use of these practices and converting Medicaid participants from fee-for-service to managed care plans. Similar legislation to complement clinical practice guidelines is expected to be enacted in other states. It is vital that practitioners comprehend the new guidelines and make appropriate adjustments in their opioid prescribing habits. PMID- 26369589 TI - Twelve- and 52-week safety of albuterol multidose dry powder inhaler in patients with persistent asthma. AB - OBJECTIVE: Evaluate the safety of albuterol multidose dry powder inhaler (MDPI), a novel, inhalation-driven device that does not require coordination of actuation with inhalation, in patients with persistent asthma. METHODS: We report pooled safety data from two 12-week, multicenter, randomized, double-blind, repeat-dose, parallel-group studies and the 12-week double-blind phase of a 52-week multicenter safety study as well as safety data from the 40-week open-label phase of the 52-week safety study. In each study, eligible patients aged >= 12 years with persistent asthma received placebo MDPI or albuterol MDPI 180 ug (2 inhalations * 90 ug/inhalation) 4 times/day for 12 weeks. In the 40-week open label phase of the 52-week safety study, patients received albuterol MDPI 180 MUg (2 inhalations * 90 MUg/inhalation) as needed (PRN). RESULTS: During both 12-week studies and the 12-week double-blind phase of the 52-week study, adverse events were more common with placebo MDPI (50%; n = 333) than albuterol MDPI (40%; n = 321); most frequent were upper respiratory tract infection (placebo MDPI 11%, albuterol MDPI 10%), nasopharyngitis (6%, 5%), and headache (6%, 4%). Incidences of beta2-agonist-related events (excluding headache) during the pooled 12-week dosing periods were low (<= 1%) in both groups. The safety profile with albuterol MDPI PRN during the 40-week open-label phase [most frequent adverse events: nasopharyngitis (12%), sinusitis (11%), upper respiratory tract infection (9%)] was similar to that observed during the 12-week pooled analysis. CONCLUSIONS: The safety profile of albuterol MDPI 180 MUg in these studies was comparable with placebo MDPI and consistent with the well-characterized profile of albuterol in patients with asthma. PMID- 26369590 TI - Phytochemical Screening: Antioxidant and Antibacterial Properties of Potamogeton Species in Order to Obtain Valuable Feed Additives. AB - The alcoholic extracts from three submerged perennial plants Potamogeton crispus L., P. pusillus L. and P. pectinatus L. were analyzed by gas chromatography-mass spectrometry coupled with solid phase microextraction (SPME-GC/MS) and by High Performance Liquid Chromatography (HPLC) and their volatile fingerprint and polyphenols composition was mutually compared. Twenty-nine chemical compounds were detected and identified in ethanolic and methanolic extracts; the highest abundance (over 5%) in descending order, was detected for 9,9-dimethyl-8,10- dioxapentacyclo (5,3,0(2,5) 0(3,5,)0 (3,6) decane (21.65%), phenol 2,6 bis (1,1 dimethyletyl) 4-1-methylpropil (20.8%), pentadecanoic acid (14.3%), 2-(5-chloro-2 Methoxyphenyl) pyrrole (8.66%), propanedioic (malonic) acid 2-(4-methylphenyl) sulfonyl ethylidene (5.77%), 2 hydroxy-3 tert butyl-5-isopropyl-6 methyl phenyl ketone (5.76%). The highest total polyphenols and flavonoids content was found in the methanolic extract of P. crispus (112.5+/-0.5 mg tannic acid/g dry extract; 64.2+/-1.2 mg quercitin/g dry extract). Antioxidant activities (2,2-difenil-1 picrilhidrazil, hydrogen peroxide and reducing power assays) of obtained extracts are comparable with the standard compounds, butylated hydroxytoluene, rutin and ascorbic acid. Antibacterial efficiency of methanolic extracts was notably demonstrated against Gram negative (Escherichia coli, Enterobacter hormaechei) and Gram positive bacteria (Enterococcus casseliflavus). The data reported for the first time for Romanian Potamogeton species, provides extensive support for the chemical investigations of these plants of the aquatic anthropogene ecosystems in order to obtain valuable bioadditives for animal feed and/or pharmaceutical/food industry. PMID- 26369591 TI - Lubricant and Bactericidal Properties of Calcium Salts of Fatty Acids: Effect of Degree of Unsaturation. AB - Fatty acids containing a C18 alkyl chain such as stearic acid (C18:0 fatty acid), oleic acid (C18:1 fatty acid) and linoleic acid (C18:2 fatty acid) are common emulsifiers in skin-care products and cosmetics and are also used in skin cleansers. In this study, we prepared calcium salts (Ca salts) of the above fatty acids to determine the effect of the degree of unsaturation of the alkyl chain. Scanning electron microscopy images and X-ray diffraction patterns show that C18:0 and C18:1 fatty acid Ca salts are plate-shaped, lamellar-crystalline powder, while C18:2 fatty acid Ca salt is amorphous powder. Therefore, C18:2 fatty acid Ca salt exhibits a lower lubrication ability than do C18:0 and C18:1 fatty acid Ca salts. In addition, the bactericidal ability against Staphylococcus aureus, Staphylococcus epidermidis and Propionibacterium acnes improved with increasing degree of unsaturation. These findings suggest that Ca salts of unsaturated fatty acids have potential applications in cleansing and cosmetic products. PMID- 26369592 TI - Chemical Compositions and Aroma Evaluation of Volatile Oil from the Industrial Cultivation Medium of Enterococcus faecalis. AB - Enterococcus faecalis is one of the major lactic acid bacterium (LAB) species colonizing the intestines of animals and humans. The characteristic odor of the volatile oils obtained from both the liquid medium after incubation (MAI) and liquid medium before incubation (MBI) in the cultivation process of E. faecalis was investigated to determine the utility of the liquid medium. In total, fifty six and thirty-two compounds were detected in the volatile oils from the MAI (MAI oil) and MBI (MBI oil), respectively. The principle components of MAI oil were 2,5-dimethylpyrazine (19.3%), phenylacetaldehyde (19.3%), and phenylethyl alcohol (9.3%). The aroma extract dilution analysis (AEDA) method was performed using gas chromatography-olfactometry (GC-O). The total number of aroma-active compounds identified in the volatile oil from MBI and MAI was thirteen compounds; in particular, 5-methyl-2-furanmethanol, phenylacetaldehyde, and phenylethyl alcohol were the most primary aroma-active compounds in MAI oil. These results imply that the industrial cultivation medium after incubation of E. faecalis may be utilized as a source of volatile oils. PMID- 26369593 TI - Enhanced Extraction of Oil from Flaxseed (Linum usitatissimum L.) Using Microwave Pre-treatment. AB - The effect of microwave (MW) pre-treatment on the extraction of flaxseed oil was investigated by hot extraction (HE). Nine MW pre-treatments were established, combining three MW radiation intensities (12, 18 and 24 W/g) and three MW radiation times of pre-treatment (90, 150 and 210 s). Extraction yield increased significantly with MW pre-treatments of flaxseed, and a max oil extraction yield (78.11%) can be obtained using MW pre-treatment at 18 W/g for 210 s. Scanning electronic microscopy showed that the microstructure of treated samples (18 W/g and 210 s) was modified compared with that of untreated samples. The fatty acid compositions (palmitic acid 5.85+/-0.01%, stearic acid 3.00+/-0.01%, oleic acid 17.64+/-0.07%, linoleic acid 16.16+/-0.06%, and linolenic acid 57.37+/-1.32%) of the oils extracted by the MW pre-treatments HE were similar with that of the conventional HE method. Results showed that fatty acid compositions of flaxseed oil were not affected by MW pre-treatments. PMID- 26369594 TI - Optimization of an Indirect Enzymatic Method for the Simultaneous Analysis of 3 MCPD, 2-MCPD, and Glycidyl Esters in Edible Oils. AB - We developed a novel, indirect enzymatic method for the analysis of fatty acid esters of 3-monochloro-1,2-propanediol (3-MCPD), 2-monochloro-1,3-propanediol (2 MCPD), and glycidol (Gly) in edible oils and fats. Using this method, the ester analytes were rapidly cleavaged by Candida rugosa lipase at room temperature for 0.5 h. As a result of the simultaneous hydrolysis and bromination steps, 3-MCPD esters, 2-MCPD esters, and glycidyl esters were converted to free 3-MCPD, 2-MCPD, and 3-monobromo-1,2-propanediol (3-MBPD), respectively. After the addition of internal standards, the mixtures were washed with hexane, derivatized with phenylboronic acid, and analyzed by gas chromatography-mass spectrometer (GC-MS). The analytical method was evaluated in preliminary and feasibility studies performed by 13 laboratories. The preliminary study from 4 laboratories showed the reproducibility (RSD R ) of < 10% and recoveries in the range of 102-111% for the spiked 3-MCPD and 2-MCPD in extra virgin olive (EVO) oil, semi-solid palm oil, and solid palm oil. However, the RSDR and recoveries of Gly in the palm oil samples were not satisfactory. The Gly content of refrigerated palm oil samples decreased whereas the samples at room temperature were stable for three months, and this may be due to the depletion of Gly during cold storage. The feasibility studies performed by all 13 laboratories were conducted based on modifications of the shaking conditions for ester cleavage, the conditions of Gly bromination, and the removal of gel formed by residual lipase. Satisfactory RSDR were obtained for EVO oil samples spiked with standard esters (4.4% for 3-MCPD, 11.2% for 2-MCPD, and 6.6% for Gly). PMID- 26369595 TI - Quality and Composition of Virgin Olive Oil from Varietties Grown in Castilla-La Mancha (Spain). AB - The regulated physicochemical quality parameters (free acidity, peroxide value and UV absorption characteristics), sensory parameters (median of fruity, median of defect, panel classification, bitterness and pungency), stability parameters (total phenols and oxidative stability at 100 degrees C) and chemical composition (fatty acids, sterols and triterpenic dialcohols) of virgin olive oils obtained from 12 olive varieties cultivated in 6 of the most representative zones of Castilla-La Mancha (La Alcarria, Campos de Calatrava, Campos de Hellin, Campos de Montiel, Montes de Toledo and Sierra de Alcaraz) were evaluated. The varieties Cornicabra and Picual showed remarkable total polyphenols content and high stability, in contrast with Arbequina. The other less common varieties were in between these two groups. Cornicabra and Picual showed also high oleic and low linoleic acids content, while Arbequina showed low oleic, high linoleic high palmitic and high palimitoleic acid content. The varieties Benizal and Cornicabra showed very high campesterol content. Benizal stood out by its high stigmasterol, low apparent beta-sitosterol and low total sterols content, and the latter was below the established limit for olive oil. Triterpenic dialcohol content was significantly lower for Arbequina than for Cornicabra. PMID- 26369596 TI - Chemical Composition of the Essential Oil of the Boreal Relict of Pyrola rotundifolia L. from Northern Kazakhstan. AB - In Kazakhstan Pyrola rotundifolia L. is the plant-relict in the flora of insular pine forests of the region of low hillocks and declivities in Kazakhstan - a group of insular pine forests of Kokshetau, Bayanaul and Karkaralinsk. In this study, the essential oils from dried aerial parts of P. rotundifolia, collected in natural habitats of the State National Natural Park "Burabay" (Akmola oblast, Northern Kazakhstan), were extracted by hydrodistillation and analyzed by gas chromatography - mass spectrometry. The yield of the essential oil amounted to 0.057 % in relation to the mass of the air-dry raw material. The major components in dried plant oil were 2,6-dimethyl-1,4-naphthoquinone (12.99-93.49%) and dibutyl phthalate (4.42-40.48%), depending on the growth conditions. PMID- 26369597 TI - Assessment of Thermal and Textural Characteristics and Consumer Preferences of Lemon and Strawberry Flavored Fish Oil Organogels. AB - In this study, strawberry and lemon flavored fish oil organogels (FOO) were prepared with beeswax as the organogelator. The physical, thermal and textural characteristics as well as the consumer preferences of the flavored organogels were determined in comparison with fish oil and FOO containing no flavor. Furthermore, the stability of the organogels was evaluated during 90 day storage at 4 degrees C. The results revealed that, structurally stable fish oil organogels as spreadable products might be formed and that flavoring of the gels enhances consumer preference. Thus, flavoring of fish oil organogels could be a challenge in increasing the consumption of fish oil. PMID- 26369598 TI - Accumulation of Paprika Carotenoids in Human Plasma and Erythrocytes. AB - The accumulation (incorporation) of paprika carotenoid in human plasma and erythrocytes was investigated. A paprika carotenoid supplement (14 mg/day) was ingested for 4 weeks by 5 young healthy volunteers (3 men and 2 women). After 2 weeks of carotenoid ingestion, the carotenoid levels in plasma and erythrocytes increased by 1.2-fold and 2.2-fold, respectively. Characteristic carotenoids found in paprika (capsanthin, cucurbitaxanthin A, and cryptocapsin) were detected in both plasma and erythrocytes. An oxidative metabolite of capsanthin (capsanthone) was also found in both plasma and erythrocytes. PMID- 26369599 TI - Chemical Composition and Bioactivity of Essential Oil of Atalantia guillauminii against Three Species Stored Product Insects. AB - The toxic and repellent activities of the essential oil extracted from the leaves of Atalantia guillauminii Swingle were evaluated against three stored product insects, red flour beetles (Tribolium castaneum), cigarette beetles (Lasioderma serricorne) and booklice (Liposcelis bostrychophila). The essential oil obtained by hydrodistillation was investigated by GC-MS. The main constituents of the essential oil were beta-thujene (27.18%), elemicin (15.03%), eudesma-3, 7(11) diene (9.64%), followed by (-)-4-terpeniol (6.70%) and spathulenol (5.25%). The crude oil showed remarkable contact toxicity against T. castaneum, L. serricorne adults and L. bostrychophila with LD50 values of 17.11, 24.07 ug/adult and 55.83 ug/cm(2) respectively and it also displayed strong fumigant toxicity against T. castaneum, L. serricorne adults with LC50 values of 17.60 and 12.06 mg/L respectively, while weak fumigant toxicity against L. bostrychophila with a LC50 value of 16.75 mg/L. Moreover, the essential oil also exhibited the same level repellency against the three stored product insects, relative to the positive control, DEET. At the same concentrations, the essential oil was more repellent to T. castaneum than to L. serricorne. Thus, the essential oil of A. guillauminii may be potential to be developed as a new natural fumigant/repellent in the control of stored product insects. PMID- 26369600 TI - Early adversity, neural development, and inflammation. AB - Early adversity is a risk factor for poor mental and physical health. Although altered neural development is believed to be one pathway linking early adversity to psychopathology, it has rarely been considered a pathway linking early adversity to poor physical health. However, this is a viable pathway because the central nervous system is known to interact with the immune system via the hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system (ANS). In support of this pathway, early adversity has been linked to changes in neural development (particularly of the amygdala, hippocampus, and prefrontal cortex), HPA axis and ANS dysregulation, and higher levels of inflammation. Inflammation, in turn, can be detrimental to physical health when prolonged. In this review, we present these studies and consider how altered neural development may be a pathway by which early adversity increases inflammation and thus risk for adverse physical health outcomes. PMID- 26369601 TI - Streptococcus equi meningitis. PMID- 26369602 TI - Composition of human faecal microbiota in resistance to Campylobacter infection. AB - In mice, specific species composition of gut microbiota enhances susceptibility to Campylobacter jejuni but little is known about the specific composition of the human gut microbiota in providing protection from infections caused by enteropathogens. Healthy adult individuals, who travelled in groups from Sweden to destinations with an estimated high risk for acquisition of Campylobacter infection, were enrolled. Faecal samples, collected before travelling and after returning home, were cultured for bacterial enteropathogens, and analysed for Campylobacter by PCR and for the species composition of the microbiota by 16S amplicon massive parallel sequencing. The microbiota compositions were compared between persons who became infected during their travel and those who did not. A total of 63 participants completed the study; 14 became infected with Campylobacter, two with Salmonella and 47 remained negative for the enteropathogens tested. After exclusion of samples taken after antimicrobial treatment, 49 individuals were included in the final analyses. Intra-individual stability of the microbiota was demonstrated for samples taken before travelling. The original diversity of the faecal microbiota was significantly lower among individuals who later became infected compared with those who remained uninfected. The relative abundances of bacteria belonging to the family Lachnospiraceae, and more specifically its two genera Dorea and Coprococcus, were significantly higher among those who remained uninfected. The travel-related infection did not significantly modify the faecal microbiota composition. Species composition of human gut microbiota is important for colonization resistance to Campylobacter infection. Especially individuals with a lower diversity are more susceptible to Campylobacter infection. PMID- 26369603 TI - Impact of Candida spp. isolation in the respiratory tract in patients with intensive care unit-acquired pneumonia. AB - In immunocompetent patients with nosocomial pneumonia, the relationship between Candida spp. isolation in respiratory samples and outcomes or association with other pathogens is controversial. We therefore compared the characteristics and outcomes of patients with intensive care unit-acquired pneumonia (ICUAP), with or without Candida spp. isolation in the respiratory tract. In this prospective non interventional study, we assessed 385 consecutive immunocompetent patients with ICUAP, according to the presence or absence of Candida spp. in lower respiratory tract samples. Candida spp. was isolated in at least one sample in 82 (21%) patients. Patients with Candida spp. had higher severity scores and organ dysfunction at admission and at onset of pneumonia. In multivariate analysis, previous surgery, diabetes mellitus and higher Simplified Acute Physiology Score II at ICU admission independently predicted isolation of Candida spp. There were no significant differences in the rate of specific aetiological pathogens, the systemic inflammatory response, and length of stay between patients with and without Candida spp. Mortality was also similar, even adjusted for potential confounders in propensity-adjusted multivariate analyses (adjusted hazard ratio 1.08, 95% CI 0.57-2.05, p 0.80 for 28-day mortality and adjusted hazard ratio 1.38, 95% CI 0.81-2.35, p 0.24 for 90-day mortality). Antifungal therapy was more frequently prescribed in patients with Candida spp. in respiratory samples but did not influence outcomes. Candida spp. airway isolation in patients with ICUAP is associated with more initial disease severity but does not influence outcomes in these patients, regardless of the use or not of antifungal therapy. PMID- 26369604 TI - Overcoming the obstacles of implementing infection prevention and control guidelines. AB - Reasons for a successful or unsuccessful implementation of infection prevention and control (IPC) guidelines are often multiple and interconnected. This article reviews key elements from the national to the individual level that contribute to the success of the implementation of IPC measures and gives perspectives for improvement. Governance approaches, modes of communication and formats of guidelines are discussed with a view to improve collaboration and transparency among actors. The culture of IPC influences practices and varies according to countries, specialties and healthcare providers. We describe important contextual aspects, such as relationships between actors and resources and behavioural features including professional background or experience. Behaviour change techniques providing goal-setting, feedback and action planning have proved effective in mobilizing participants and may be key to trigger social movements of implementation. The leadership of international societies in coordinating actions at international, national and institutional levels using multidisciplinary approaches and fostering collaboration among clinical microbiology, infectious diseases and IPC will be essential for success. PMID- 26369605 TI - Clinical assessment of oral malodor using autofluorescence of tongue coating. AB - OBJECTIVES: The aim of this study was to evaluate whether a new method using quantitative light-induced fluorescence-digital (QLF-D) was appropriate for the diagnosis of oral malodor by quantifying the fluorescence of tongue coating. METHODS: This study examined 103 healthy subjects who have an oral malodor as a main complaint. The levels of oral malodor were measured by organoleptic scores (OLS) and volatile sulfur compound (VSC) levels. The fluorescent tongue coating images captured by QLF-D were quantified as the integrated fluorescence score (IF score) by multiplying the intensity and area of fluorescence. The correlations between the fluorescence parameters and OLS as well as VSC levels and the diagnostic accuracy of the IF score were evaluated. RESULTS: The IF score of tongue coating showed a significant positive correlation with the OLS (r=0.54, p<0.01) and the VSC levels (r=0.49, p<0.01). This score was significantly differed with the level of oral malodor (p<0.001), and its AUC was 0.72 in identifying the patient with definite oral malodor (>=OLS 2). CONCLUSIONS: A new method quantifying tongue coating fluorescence detected by QLF-D can be used to diagnose oral malodor and assess its severity in the clinical practice. PMID- 26369606 TI - ALA-induced photodynamic effect on vitality, apoptosis, and secretion of vascular endothelial growth factor (VEGF) by colon cancer cells in normoxic environment in vitro. AB - BACKGROUND: Cancer therapy is often based on combination of conventional methods of cancer treatment with immunotherapy. Photodynamic therapy (PDT) is one of the immunomodulating methods used in oncology. We examined how PDT influences the secretory activity of colon cancer cells in vitro, especially the secretion of vascular endothelial growth factor (VEGF) in aerobic conditions. METHODS: We used two cancer cell lines with different malignancy potentials: a metastatic SW620 line and a non-metastatic SW480 line. In the first stage of the experiment, we exposed each cell line to three different concentrations of photosensitizer's precursor: 5-aminolevulinic acid (ALA) and varying levels of light radiation, after which we assessed cell viability and apoptosis induction in these lines, using the MTT and LDH assays. Then, we determined the secretion of VEGF by these cells in aerobic conditions and under the ALA-PDT parameters at which cells presented the highest viability. RESULTS: Photodynamic treatment with ALA did not influence on VEGF secretion by the non-metastatic SW480 cells, but caused a decrease in VEGF secretion by the metastatic SW 620 cell line by 29% (p<0.05). SW 620 cell line secreted more actively VEGF than the SW480 cells, both before and after photo dynamic therapy (p<0.05). CONCLUSION: The outcome of this in vitro study presented a beneficial effect of ALA-PDT, resulting in a decrease of VEGF secretion in the more malignant SW620 cell lines. Further studies should be considered to confirm the clinical relevance of this finding. PMID- 26369607 TI - Early stages of insulin fibrillogenesis examined with ion mobility mass spectrometry and molecular modelling. AB - A prevalent type of protein misfolding causes the formation of beta-sheet-rich structures known as amyloid fibrils. Research into the mechanisms of fibril formation has implications for both disease prevention and nanoscale templating technologies. This investigation into the aggregation of insulin utilises ion mobility mass spectrometry coupled with molecular modelling to identify and characterise oligomers formed during the 'lag' phase that precedes fibril growth. High resolution mass spectrometry and collision induced dissociation is used to unequivocally assign species as m/z coincident multimers or confomers, providing a robust analytical approach that supports the use of molecular dynamics to atomistically resolve the observed oligomers. We show that insulin oligomerises to form species In where 2 <= n <= 12 and within this set of oligomers we delineate over 60 distinct conformations, the most dominant of which are compact species. Modelling trained with experimental data suggests that the dominant compact dimers are enriched in beta-sheet secondary structure and dominated by hydrophobic interactions, and provides a linear relationship between Rg and collision cross section. This approach provides detailed insight to the early stages of assembly of this much studied amyloidogenic protein, and can be used to inform models of nucleation and growth. PMID- 26369608 TI - Cerebal sulci and gyri are intrinsic landmarks for brain navigation in individual subjects: an instrument to assist neurosurgeons in preserving cognitive function in brain tumour surgery (Commentary on Zlatkina et al.). PMID- 26369609 TI - The IL-23-IL-17 axis in inflammatory arthritis. AB - The IL-23-IL-17 axis in inflammatory arthritis. Erik Lubberts. Nat. Rev. Rheumatol. 11, 415-429 (2015); published online 28 April 2015; doi:10.1038/nrrheum.2015.53. In Figure 2a of this Review, full protection against CIA was incorrectly stated as an effect of IL-17 deficiency instead of IL-17RA deficiency. PMID- 26369610 TI - Mechanisms of crystal formation in gout-a structural approach. AB - The mechanisms and sites of monosodium urate monohydrate (MSU) crystal deposition in gout have received little attention from the scientific community to date. Formalin fixation of tissues leads to the dissolution of MSU crystals, resulting in their absence from routinely processed pathological samples and hence neglect. However, modern imaging techniques-especially ultrasonography but also conventional CT and dual-energy CT-reveal that MSU crystals form at the cartilage surface as well as inside tendons and ligaments, often at insertion sites. Tophi comprise round white formations of different sizes surrounded by inflammatory tissue. Studies of fibres recovered from gouty synovial fluid indicate that these fibres are likely to be a primary site of crystal formation by templated nucleation, with crystals deposited parallel to the fibres forming transverse bands. In tophi, two areas can be distinguished: one where crystals are formed on cellular tissues and another consisting predominantly of crystals, where secondary nucleation seems to take place; this organization could explain how tophi can grow rapidly. From these observations based on a crystallographic approach, it seems that initial templated nucleation on structural fibres probably collagen-followed at some sites by secondary nucleation could explain MSU crystal deposition in gout. PMID- 26369611 TI - Autoimmunity. IRF5 mediates joint inflammation. PMID- 26369612 TI - Pharmacogenomics and cardiology: improving treatment with existing drugs. PMID- 26369614 TI - A functional progesterone receptor is required for immunomodulation, reduction of reactive gliosis and survival of oligodendrocyte precursors in the injured spinal cord. AB - The anti-inflammatory effects of progesterone have been increasingly recognized in several neuropathological models, including spinal cord inflammation. In the present investigation, we explored the regulation of proinflammatory factors and enzymes by progesterone at several time points after spinal cord injury (SCI) in male rats. We also demonstrated the role of the progesterone receptor (PR) in inhibiting inflammation and reactive gliosis, and in enhancing the survival of oligodendrocyte progenitors cells (OPC) in injured PR knockout (PRKO) mice receiving progesterone. First, after SCI in rats, progesterone greatly attenuated the injury-induced hyperexpression of the mRNAs of interleukin 1beta (IL1beta), IL6, tumor necrosis factor alpha (TNFalpha), inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2), all involved in oligodendrocyte damage. Second, the role of the PR was investigated in PRKO mice after SCI, in which progesterone failed to reduce the high expression of IL1beta, IL6, TNFalpha and IkappaB-alpha mRNAs, the latter being considered an index of reduced NF-kappaB transactivation. These effects occurred in a time framework coincident with a reduction in the astrocyte and microglial responses. In contrast to wild-type mice, progesterone did not increase the density of OPC and did not prevent apoptotic death of these cells in PRKO mice. Our results support a role of PR in: (a) the anti-inflammatory effects of progesterone; (b) the modulation of astrocyte and microglial responses and (c) the prevention of OPC apoptosis, a mechanism that would enhance the commitment of progenitors to the remyelination pathway in the injured spinal cord. PMID- 26369613 TI - Tie-2Cre mediated deletion of the vitamin D receptor gene leads to improved skeletal muscle insulin sensitivity and glucose tolerance. AB - A variety of studies have suggested that vitamin D may play a palliative role in improving insulin secretion and glucose tolerance. Endothelial cells of the microcirculation are thought to play an important role in regulating both insulin secretion and insulin sensitivity in target tissues. We have selectively deleted the vitamin D receptor (VDR) gene in endothelial cells of the murine vasculature. These mice demonstrate improved glucose tolerance, improved insulin sensitivity in skeletal muscle, but not in liver, and a reduction in expression and secretion of insulin in the pancreatic islets. Collectively, these data, taken within the context of recent publications in this field, suggest that the endothelial cell VDR plays a tonic inhibitory role in regulating glucose disposal and could prove to be a factor in controlling glucose homeostasis in the intact organism. PMID- 26369616 TI - Integration of a microfluidic chip with a size-based cell bandpass filter for reliable isolation of single cells. AB - We report a simple, efficient microfluidic array system for reliable isolation of cells. A microfluidic array chip, integrated with a size-based cell bandpass filter, provides the unprecedented capability of organizing single cells from a population containing a wide distribution of sizes. PMID- 26369615 TI - Species-specific regulation of innate immunity by vitamin D signaling. AB - While many global mechanisms of innate immune responses to pathogen threat are conserved over a vast range of species, the details of those responses and their regulation appear to be highly species-specific. An array of studies over recent years has revealed that hormonal vitamin D is an important regulator of innate immunity. In humans, the hormone-bound VDR directly induces the transcription of genes encoding antimicrobial peptides (AMPs), pattern recognition receptors and key cytokines implicated in innate immune responses. We find that the vitamin D response elements (VDREs) in a number of these human genes are highly conserved in a range of primates, but not present in rodent genes. Consistent with this, VDR target genes encoding AMPs human beta-defensin 2 (HBD2) and cathelicidin (CAMP) and the pattern recognition receptor NOD2 are induced by 1,25(OH)2D in human cells of epithelial or myeloid origin but not similarly regulated in mouse cells. In addition, while conditioned media from human epithelial cells treated with 1,25(OH)2D produced antimicrobial activity against E. coli and the lung pathogen Pseudomonas aeruginosa, no such activity was detected in conditioned media from comparable 1,25(OH)2D-treated mouse epithelial cells. Given that other work has provided evidence that 1,25(OH)2D does control innate immune responses in mouse models of disease, we discuss the species-specific similarities and differences in 1,25(OH)2D-regulated innate immunity. PMID- 26369617 TI - Neoadjuvant intralesional methotrexate in cutaneous squamous cell carcinoma: a comparative cohort study. AB - BACKGROUND: Intralesional methotrexate (MTX-il) has been used as neoadjuvant therapy for keratoacanthoma but has only been utilized in a few isolated cases of cutaneous squamous cell carcinoma as neoadjuvant therapy (cSCC). OBJECTIVES: The objective of this study was to evaluate the effectiveness in clinical practice of presurgical MTX-il infiltration to reduce the size of the cSCC. Safety and the impact on subsequent reconstructive surgical techniques was also assessment. METHODS: Single, retrospective, observational study of two historical cohorts differentiated in time. Subjects included were diagnosed with infiltrating cSCC. Patients included in group-A received neoadjuvant MTX-il and patients included in group-B underwent scheduled surgery without prior infiltration. Univariate and multivariate analyses were performed. RESULTS: Group-A patients (n = 43) showed an average reduction in the tumour area of 0.52 cm(2) , while in group-B (n = 43), the area increased by 0.49 cm(2) . A multivariate linear regression analysis demonstrated that MTX-il was the only independent variable that significantly reduced the tumour size [mean 42.6% (95% CI: 31.17-54.03)]. Tumours >=2 cm in size required significantly a lower percentage of complex reconstructions (P = 0.026). Lower lip tumours showed a higher reduction in group treated with MTX-il (P = 0.045). The only complication observed was discomfort during methotrexate infiltration (60.47%). CONCLUSIONS: Neoadjuvant MTX-il reduced the presurgical size of cSCC lesions and could simplify their subsequent surgery. PMID- 26369618 TI - MOF-derived self-assembled ZnO/Co3O4 nanocomposite clusters as high-performance anodes for lithium-ion batteries. AB - Although different kinds of metal oxide nanoparticles are extensively investigated as anode materials for lithium-ion batteries (LIBs), their cycle life and energy/power density are still not suitable for commercial applications. Metal oxides have a large storage capacity, but they suffer from low electrical conductivity and severe volume change during the charge/discharge process. Herein, we present a facile route to prepare self-assembled ZnO/Co3O4 nanocomposite clusters through calcination of preformed Prussian Blue Analogue (PBA) Zn3[Co(CN)6]2 nanospheres. These self-assembled ZnO/Co3O4 nanocomposite clusters exhibit superior lithium storage capabilities with good cycling properties. A reversible capacity of 957 mA h g(-1) was retained at a current density of 100 mA g(-1) up to 100 cycles. The enhanced electrochemical performance of the ZnO/Co3O4 nanocomposite anode can be ascribed to the rational design of the self-assembled cluster structures and the synergetic effect of two component functional nanoparticle systems. PMID- 26369620 TI - Efficient direct solar-to-hydrogen conversion by in situ interface transformation of a tandem structure. AB - Photosynthesis is nature's route to convert intermittent solar irradiation into storable energy, while its use for an industrial energy supply is impaired by low efficiency. Artificial photosynthesis provides a promising alternative for efficient robust carbon-neutral renewable energy generation. The approach of direct hydrogen generation by photoelectrochemical water splitting utilizes customized tandem absorber structures to mimic the Z-scheme of natural photosynthesis. Here a combined chemical surface transformation of a tandem structure and catalyst deposition at ambient temperature yields photocurrents approaching the theoretical limit of the absorber and results in a solar-to hydrogen efficiency of 14%. The potentiostatically assisted photoelectrode efficiency is 17%. Present benchmarks for integrated systems are clearly exceeded. Details of the in situ interface transformation, the electronic improvement and chemical passivation are presented. The surface functionalization procedure is widely applicable and can be precisely controlled, allowing further developments of high-efficiency robust hydrogen generators. PMID- 26369619 TI - Punicalagin, an active component in pomegranate, ameliorates cardiac mitochondrial impairment in obese rats via AMPK activation. AB - Obesity is associated with an increasing prevalence of cardiovascular diseases and metabolic syndrome. It is of paramount importance to reduce obesity associated cardiac dysfunction and impaired energy metabolism. In this study, the activation of the AMP-activated protein kinase (AMPK) pathway by punicalagin (PU), a major ellagitannin in pomegranate was investigated in the heart of a rat obesity model. In male SD rats, eight-week administration of 150 mg/kg pomegranate extract (PE) containing 40% punicalagin sufficiently prevented high fat diet (HFD)-induced obesity associated accumulation of cardiac triglyceride and cholesterol as well as myocardial damage. Concomitantly, the AMPK pathway was activated, which may account for prevention of mitochondrial loss via upregulating mitochondrial biogenesis and amelioration of oxidative stress via enhancing phase II enzymes in the hearts of HFD rats. Together with the normalized expression of uncoupling proteins and mitochondrial dynamic regulators, PE significantly prevented HFD-induced cardiac ATP loss. Through in vitro cultures, we showed that punicalagin was the predominant component that activated AMPK by quickly decreasing the cellular ATP/ADP ratio specifically in cardiomyocytes. Our findings demonstrated that punicalagin, the major active component in PE, could modulate mitochondria and phase II enzymes through AMPK pathway to prevent HFD-induced cardiac metabolic disorders. PMID- 26369621 TI - Nanoemulsion-based gel formulation of diclofenac diethylamine: design, optimization, rheological behavior and in vitro diffusion studies. AB - Chronic oral administration of the non-steroidal anti-inflammatory drug, diclofenac diethylamine (DDEA), is often associated with gastrointestinal ulcers and bleeding. As an alternative to oral administration, a nanoemulsion-based gel (NE gel) formulation of DDEA was developed for topical administration. An optimized formulation for the o/w nanoemulsion of oil, surfactant and cosurfactant was selected based on nanoemulsion mean droplet size, clarity, stability, and flowability, and incorporated into the gelling agent Carbopol(r) 971P. Rheological studies of the DDEA NE gel were conducted and compared to those of conventional DDEA gel and emulgel. The three gels exhibited an elastic behavior, where G' dominated G" at all frequencies, indicating the formation of strong gels. NE gel exhibited higher G' values than conventional gel and emulgel, which indicated the formation of a stronger gel network. Strat-M(r) membrane, a synthetic membrane with diffusion characteristics that are well correlated to human skin, was used for the in vitro diffusion studies. The release of DDEA from conventional gel, emulgel and NE gel showed a controlled release pattern over 12 h, which was consistent with the rheological properties of the gels. DDEA release kinetics from the three gels followed super case II transport as fitted by Korsmeyer-Peppas model. PMID- 26369622 TI - Communication About Micropollutants in Drinking Water: Effects of the Presentation and Psychological Processes. AB - This study investigates how people change their risk perception, trust, and behavior as a consequence of being informed about the occurrence of micropollutants in drinking water. Micropollutants are substances present in extremely low concentrations that might be dangerous in higher concentrations. Data were gathered in the city of Zurich, Switzerland in 2013 using a questionnaire in which the information on micropollutants was presented differently to 12 experimental groups. Data of the key constructs were gathered before and after this information, so that causal effects could be quantified by regression analyses. Affective reactions to the information turned out to be the critical mediator of changes in risk perception (operationalized as the perceived change of quality due to pollution), which is an important determinant of changes in behavior and trust. Also, direct effects of affective reactions on behavior and trust were observed. Trust before appraising risks reduces negative affective reactions; however, it also reduces perceived quality (i.e., increases risk perception) and trust after risks are appraised. The different forms of information mainly influenced the participants' affective reactions, but they also influenced perceived quality. The presentation with the least negative effects was a comparison of the intake of the substance by water with intake by food. The experimental design with repeated measurement that considers trust as a determinant and consequence of risk perception uncovered positive and negative effects of trust before appraising risks on changes of risk perception and trust due to appraising risks. PMID- 26369623 TI - How much is enough? An investigation of the relationship between haemodialysis adequacy and quality of life of elderly patients. AB - AIM: The average age of patients requiring haemodialysis is on the rise and has resulted in an increase in the number of elderly people receiving dialysis. While haemodialysis is one of the treatment options for this patient group, questions about its effectiveness have been raised. A second question centres on how much haemodialysis is actually needed to maintain quality of life (QoL). This study examined the relationship between dialysis adequacy and the QoL of elderly patients on haemodialysis. METHOD: A prospective cohort of 40 haemodialysis patients aged 75 years and above was recruited and studied over 3 months. Quality of life was assessed with the European Quality of Life-5 Dimensions questionnaire and dialysis adequacy with the urea reduction ratio (URR), and the relationship between the two examined using a simple linear regression model. RESULTS: The average age of the participants was 79.8 +/- (3.9 years; 45% were women, and diabetes was the main cause of kidney disease (42.5%). The mean URR, visual analogue scale, European Quality of Life-5 Dimensions indices score and Charlson comorbidity index scores were 78.1 +/- (5.5)%, 65.4 +/- (13.7)%, 0.7 +/- (0.27) and 6.3 +/- (2.15), respectively. There was no clear relationship between dialysis adequacy and QoL, r = 0.093. Dialysis adequacy did not significantly predict QoL (P = 0.09). CONCLUSION: There was no evidence for an association between haemodialysis adequacy and QoL in elderly patients receiving haemodialysis across a URR range of 64.0% to 88.9%. Attempts to improve dialysis adequacy beyond these levels may not be necessary for maintaining the QoL of elderly patients on dialysis. KEY MESSAGE: Modern therapy should embrace the concept of quality of life and focus more on symptom relief and optimization of self-management skills to improve the well-being of the elderly patients with ESKD. PMID- 26369624 TI - Re-examining the relationship between active cytomegalovirus (CMV) infection and acute graft-versus-host disease in allogeneic stem cell transplant recipients in the era of real-time PCR CMV assays. PMID- 26369625 TI - Clinicopathologic and survival analyses of synchronous primary endometrial and epithelial ovarian cancers. AB - AIM: The aim of the study was to describe clinicopathologic characteristics, survival outcomes and the factors associated with recurrence in patients diagnosed with synchronous primary endometrial and epithelial ovarian cancers. MATERIAL AND METHODS: In this retrospective study, 50 patients who were diagnosed with synchronous primary endometrial and epithelial ovarian cancers and underwent surgery between 1998 and 2010 were reviewed. RESULTS: In our study, the median age at the time of diagnosis was 53 years (range 28-79). The most common presenting symptom was abnormal uterine bleeding with a ratio of 36%. Fifty-four percent of the patients had endometrioid type endometrial cancer and endometrioid type ovarian cancer. All patients were surgically staged and the majority of the patients were in stage I for both endometrial cancer (58%) and ovarian cancer (60%). Nearly one-third (32%) of the patients had a recurrence during the follow up period and by Cox regression analysis the level of cancer antigen 125 (P = 0.023) at diagnosis, serous or clear-cell histopathologic type ovarian cancer (P = 0.029) and stage of endometrial cancer above I (P = 0.048) were found to be independent risk factors associated with development of recurrence. Patients with endometrioid type endometrium histology and endometrioid type ovarian histology had favorable prognosis with 120.00 months mean disease-free survival and 92% disease-free survival rate at 36 months. CONCLUSION: In our cohort, we found that endometrioid/endometrioid type synchronous primary endometrial and ovarian cancer had different clinical histopathologic characteristics and favorable prognosis compared to the other histologic types of these cancers. Histopathologic type of the ovarian cancer component, stage of endometrial cancer and level of cancer antigen 125 at diagnosis were observed to have a great influence on the development of recurrence and survival of synchronous primary carcinomas of the endometrium and ovary. PMID- 26369626 TI - Effects of fatigue and surface instability on neuromuscular performance during jumping. AB - It has previously been shown that fatigue and unstable surfaces affect jump performance. However, the combination thereof is unresolved. Thus, the purpose of this study was to examine the effects of fatigue and surface instability on jump performance and leg muscle activity. Twenty elite volleyball players (18 +/- 2 years) performed repetitive vertical double-leg box jumps until failure. Before and after a fatigue protocol, jump performance (i.e., jump height) and electromyographic activity of selected lower limb muscles were recorded during drop jumps (DJs) and countermovement jumps (CMJs) on a force plate on stable and unstable surfaces (i.e., balance pad on top of force plate). Jump performance (3 7%; P < 0.05; 1.14 <= d <= 2.82), and muscle activity (2-27%; P < 0.05; 0.59 <= d <= 3.13) were lower following fatigue during DJs and CMJs, and on unstable compared with stable surfaces during DJs only (jump performance: 8%; P < 0.01; d = 1.90; muscle activity: 9-25%; P < 0.05; 1.08 <= d <= 2.54). No statistically significant interactions of fatigue by surface condition were observed. Our findings revealed that fatigue impairs neuromuscular performance during DJs and CMJs in elite volleyball players, whereas surface instability affects neuromuscular DJ performance only. Absent fatigue * surface interactions indicate that fatigue-induced changes in jump performance are similar on stable and unstable surfaces in jump-trained athletes. PMID- 26369627 TI - Durable engraftment and correction of hematological abnormalities in children with congenital amegakaryocytic thrombocytopenia following myeloablative umbilical cord blood transplantation. AB - The use of HSCT is the only potentially curative treatment for CAMT, but access is limited by the availability of suitable donors. We report five consecutive patients with CAMT who received MAC and partially HLA-mismatched, UCBT (unrelated, n = 4). Median times to neutrophil (>500/MUL) and platelet (>=20 000 and >=50 000/MUL) engraftment were 19, 57, and 70 days, respectively. Acute GvHD, grade II, developed in one patient, who subsequently developed limited chronic GvHD. At median follow-up of 14 yr, all patients are alive with sustained donor cell engraftment. To our knowledge, this is the largest single-center series of UCBT for patients with this disease and suggests that UCBT is a successful curative option for patients with CAMT. PMID- 26369628 TI - Quinidine in the treatment of KCNT1-positive epilepsies. AB - We report 2 patients with drug-resistant epilepsy caused by KCNT1 mutations who were treated with quinidine. Both mutations manifested gain of function in vitro, showing increased current that was reduced by quinidine. One, who had epilepsy of infancy with migrating focal seizures, had 80% reduction in seizure frequency as recorded in seizure diaries, and partially validated by objective seizure evaluation on EEG. The other, who had a novel phenotype, with severe nocturnal focal and secondary generalized seizures starting in early childhood with developmental regression, did not improve. Although quinidine represents an encouraging opportunity for therapeutic benefits, our experience suggests caution in its application and supports the need to identify more targeted drugs for KCNT1 epilepsies. PMID- 26369629 TI - Emergency Preparedness and Disaster Response: There's An App for That. AB - INTRODUCTION: Smartphone applications (or apps) are becoming increasingly popular with emergency responders and health care providers, as well as the public as a whole. There are thousands of medical apps available for Smartphones and tablet computers, with more added each day. These include apps to view textbooks, guidelines, medication databases, medical calculators, and radiology images. Hypothesis/Problem With an ever expanding catalog of apps that relate to disaster medicine, it is hard for both the lay public and responders to know where to turn for effective Smartphone apps. A systematic review of these apps was conducted. METHODS: A search of the Apple iTunes store (Version 12; Apple Inc.; Cupertino, California USA) was performed using the following terms obtained from the PubMed Medical Subject Headings Database: Emergency Preparedness, Emergency Responders, Disaster, Disaster Planning, Disaster Medicine, Bioterrorism, Chemical Terrorism, Hazardous Materials (HazMat), and the Federal Emergency Management Agency (FEMA). After excluding any unrelated apps, a working list of apps was formed and categorized based on topics. Apps were grouped based on applicability to responders, the lay public, or regional preparedness, and were then ranked based on iTunes user reviews, value, relevance to audience, and user interface. RESULTS: This search revealed 683 applications and was narrowed to 219 based on relevance to the field. After grouping the apps as described above, and subsequently ranking them, the highest quality apps were determined from each group. The Community Emergency Response Teams and FEMA had the best apps for National Disaster Medical System responders. The Centers for Disease Control and Prevention (CDC) had high-quality apps for emergency responders in a variety of fields. The National Library of Medicine's Wireless Information System for Emergency Responders (WISER) app was an excellent app for HazMat responders. The American Red Cross had the most useful apps for natural disasters. Numerous valuable apps for public use, including alert apps, educational apps, and a well made regional app, were also identified. CONCLUSION: Smartphone applications are fast becoming essential to emergency responders and the lay public. Many high quality apps existing in various price ranges and serving different populations were identified. This field is changing rapidly and it deserves continued analysis as more apps are developed. PMID- 26369630 TI - Nuclear Trapping through Inhibition of Exosomal Export by Indomethacin Increases Cytostatic Efficacy of Doxorubicin and Pixantrone. AB - PURPOSE: Although R-CHOP-based immunochemotherapy cures significant proportions of patients with aggressive B-cell lymphoma, tumor cell susceptibility to chemotherapy varies, with mostly fatal outcome in cases of resistant disease. We and others have shown before that export of cytostatic drugs contributes to drug resistance. Now we provide a novel approach to overcome exosome-mediated drug resistance in aggressive B-cell lymphomas. EXPERIMENTAL DESIGN: We used well established centrifugation protocols to purify exosomes from DLBCL cell lines and detected anthracyclines using FACS and HPLC. We used shRNA knockdown of ABCA3 to determine ABCA3 dependence of chemotherapy susceptibility and monitored ABCA3 expression after indomethacin treatment using qPCR. Finally, we established an in vivo assay using a chorioallantoic membrane (CAM) assay to determine the synergy of anthracycline and indomethacin treatment. RESULTS: We show increased efficacy of the anthracycline doxorubicin and the anthracenedione pixantrone by suppression of exosomal drug resistance with indomethacin. B-cell lymphoma cells in vitro efficiently extruded doxorubicin and pixantrone, in part compacted in exosomes. Exosomal biogenesis was critically dependent on the expression of the ATP-transporter A3 (ABCA3). Genetic or chemical depletion of ABCA3 augmented intracellular retention of both drugs and shifted the subcellular drug accumulation to prolonged nuclear retention. Indomethacin increased the cytostatic efficacy of both drugs against DLBCL cell lines in vitro and in vivo in a CAM assay. CONCLUSIONS: We propose pretreatment with indomethacin toward enhanced antitumor efficacy of anthracyclines and anthracenediones. PMID- 26369631 TI - Sensitivity of KRAS-Mutant Colorectal Cancers to Combination Therapy That Cotargets MEK and CDK4/6. AB - PURPOSE: The emerging need for rational combination treatment approaches led us to test the concept that cotargeting MEK and CDK4/6 would prove efficacious in KRAS-mutant (KRAS(mt)) colorectal cancers, where upregulated CDK4 and hyperphosphorylated retinoblastoma (RB) typify the vast majority of tumors. EXPERIMENTAL DESIGN: Initial testing was carried out in the HCT-116 tumor model, which is known to harbor a KRAS mutation. Efficacy studies were then performed with five RB(+) patient-derived colorectal xenograft models, genomically diverse with respect to KRAS, BRAF, and PIK3CA mutational status. Tolerance, efficacy, and pharmacodynamic evaluation of target modulation were evaluated in response to daily dosing with either agent alone or concurrent coadministration. RESULTS: Synergy was observed in vitro when HCT-116 cells were treated over a broad range of doses of trametinib and palbociclib. Subsequent in vivo evaluation of this model showed a higher degree of antitumor activity resulting from the combination compared to that achievable with single-agent treatment. Testing of colorectal patient-derived xenograft (PDX) models further showed that combination of trametinib and palbociclib was well tolerated and resulted in objective responses in all KRAS(mt) models tested. Stasis was observed in a KRAS/BRAF wild-type and a BRAF(mt) model. CONCLUSIONS: Combination of trametinib and palbociclib was well tolerated and highly efficacious in all three KRAS-mutant colorectal cancer PDX models tested. Promising preclinical activity seen here supports clinical evaluation of this treatment approach to improve therapeutic outcome for patients with metastatic colorectal cancer. PMID- 26369632 TI - SRC3 Phosphorylation at Serine 543 Is a Positive Independent Prognostic Factor in ER-Positive Breast Cancer. AB - PURPOSE: The steroid receptor coactivator SRC3 is essential for the transcriptional activity of estrogen receptor alpha (ERalpha). SRC3 is sufficient to cause mammary tumorigenesis, and has also been implicated in endocrine resistance. SRC3 is posttranslationally modified by phosphorylation, but these events have not been investigated with regard to functionality or disease association. Here, we investigate the spatial selectivity of SRC3-pS543/DNA binding over the human genome and its expression in primary human breast cancer in relation with outcome. EXPERIMENTAL DESIGN: Chromatin immunoprecipitation, coupled with sequencing, was used to determine the chromatin binding patterns of SRC3-pS543 in the breast cancer cell line MCF7 and two untreated primary breast cancers. IHC was used to assess the expression of SRC3 and SRC3-pS543 in 1,650 primary breast cancers. The relationship between the expression of SRC3 and SRC3 pS543, disease-free survival (DFS), and breast cancer specific survival (BCSS) was assessed. RESULTS: Although total SRC3 is selectively found at enhancer regions, SRC3-pS543 is recruited to promoters of ERalpha responsive genes, both in the MCF7 cell line and primary breast tumor specimens. SRC3-pS543 was associated with both improved DFS (P = 0.003) and BCSS (P = 0.001) in tamoxifen untreated high-risk patients, such a correlation was not seen in tamoxifen treated cases, the interaction was statistically significant (P = 0.001). Multivariate analysis showed SRC3-pS543 to be an independent prognostic factor. CONCLUSIONS: Phosphorylation of SRC3 at S543 affects its genomic interactions on a genome-wide level, where SRC3-pS543 is selectively recruited to promoters of ERalpha-responsive genes. SRC3-pS543 is a prognostic marker, and a predictive marker of response to endocrine therapy. PMID- 26369633 TI - Parental and peer support in adolescents with a chronic condition: a typological approach and developmental implications. AB - Research has consistently demonstrated that contextual support is crucial towards the psychological functioning of adolescents with chronic conditions. However, the literature has predominantly focused on parental support instead of adopting an integrated approach to parental and peer support. The present manuscript with two longitudinal studies in adolescents with Type 1 diabetes and congenital heart disease examined the extent to which different clusters of maternal, paternal, and peer support at baseline were related to well- and ill-being over time. In both studies, four clusters emerged: combined support, parental support, peer support, and lack of support. Follow-up longitudinal analyses indicated that especially combined support from parents and peers proved to be of crucial importance towards psychological functioning. The present studies demonstrated the value of a typological approach for assessing social support in adolescents with chronic conditions. In addition to focusing on parental support, future research should assess peer support as well in these adolescents. PMID- 26369634 TI - Validation of Ultrasound Elastography Imaging for Nondestructive Characterization of Stiffer Biomaterials. AB - Ultrasound elastography (UE) has been widely used as a "digital palpation" tool to characterize tissue mechanical properties in the clinic. UE benefits from the capability of noninvasively generating 2-D elasticity encoded maps. This spatial distribution of elasticity can be especially useful in the in vivo assessment of tissue engineering scaffolds and implantable drug delivery platforms. However, the detection limitations have not been fully characterized and thus its true potential has not been completely discovered. Characterization studies have focused primarily on the range of moduli corresponding to soft tissues, 20-600 kPa. However, polymeric biomaterials used in biomedical applications such as tissue scaffolds, stents, and implantable drug delivery devices can be much stiffer. In order to explore UE's potential to assess mechanical properties of biomaterials in a broader range of applications, this work investigated the detection limit of UE strain imaging beyond soft tissue range. To determine the detection limit, measurements using standard mechanical testing and UE on the same polydimethylsiloxane samples were compared and statistically evaluated. The broadest detection range found based on the current optimized setup is between 47 kPa and 4 MPa which exceeds the modulus of normal soft tissue suggesting the possibility of using this technique for stiffer materials' mechanical characterization. The detectable difference was found to be as low as 157 kPa depending on sample stiffness and experimental setup. PMID- 26369635 TI - In Situ Quantification of Surface Chemistry in Porous Collagen Biomaterials. AB - Cells inside a 3D matrix (such as tissue extracellular matrix or biomaterials) sense their insoluble environment through specific binding interactions between their adhesion receptors and ligands present on the matrix surface. Despite the critical role of the insoluble matrix in cell regulation, there exist no widely applicable methods for quantifying the chemical stimuli provided by a matrix to cells. Here, we describe a general-purpose technique for quantifying in situ the density of ligands for specific cell adhesion receptors of interest on the surface of a 3D matrix. This paper improves significantly the accuracy of the procedure introduced in a previous publication by detailed marker characterization, optimized staining, and improved data interpretation. The optimized methodology is utilized to quantify the ligands of integrins alpha 1 beta 1, alpha 2 beta 1 on two kinds of matched porous collagen scaffolds, which are shown to possess significantly different ligand density, and significantly different ability to induce peripheral nerve regeneration in vivo. Data support the hypothesis that cell adhesion regulates contractile cell phenotypes, recently shown to be inversely related to organ regeneration. The technique provides a standardized way to quantify the surface chemistry of 3D matrices, and a means for introducing matrix effects in quantitative biological models. PMID- 26369636 TI - Assessment of Hemodynamic Conditions in the Aorta Following Root Replacement with Composite Valve-Conduit Graft. AB - This paper presents the analysis of detailed hemodynamics in the aortas of four patients following replacement with a composite bio-prosthetic valve-conduit. Magnetic resonance image-based computational models were set up for each patient with boundary conditions comprising subject-specific three-dimensional inflow velocity profiles at the aortic root and central pressure waveform at the model outlet. Two normal subjects were also included for comparison. The purpose of the study was to investigate the effects of the valve-conduit on flow in the proximal and distal aorta. The results suggested that following the composite valve conduit implantation, the vortical flow structure and hemodynamic parameters in the aorta were altered, with slightly reduced helical flow index, elevated wall shear stress and higher non-uniformity in wall shear compared to normal aortas. Inter-individual analysis revealed different hemodynamic conditions among the patients depending on the conduit configuration in the ascending aorta, which is a key factor in determining post-operative aortic flow. Introducing a natural curvature in the conduit to create a smooth transition between the conduit and native aorta may help prevent the occurrence of retrograde and recirculating flow in the aortic arch, which is particularly important when a large portion or the entire ascending aorta needs to be replaced. PMID- 26369638 TI - An Overview of Mechanical Properties and Material Modeling of Polylactide (PLA) for Medical Applications. AB - This article provides an overview of the connection between the microstructural state and the mechanical response of various bioresorbable polylactide (PLA) devices for medical applications. PLLA is currently the most commonly used material for bioresorbable stents and sutures, and its use is increasing in many other medical applications. The non-linear mechanical response of PLLA, due in part to its low glass transition temperature (T g ~ 60 degrees C), is highly sensitive to the molecular weight and molecular orientation field, the degree of crystallinity, and the physical aging time. These microstructural parameters can be tailored for specific applications using different resin formulations and processing conditions. The stress-strain, deformation, and degradation response of a bioresorbable medical device is also strongly dependent on the time history of applied loads and boundary conditions. All of these factors can be incorporated into a suitable constitutive model that captures the multiple physics that are involved in the device response. Currently developed constitutive models already provide powerful computations simulation tools, and more progress in this area is expected to occur in the coming years. PMID- 26369637 TI - Correlation of Subchondral Bone Density and Structure from Plain Radiographs with Micro Computed Tomography Ex Vivo. AB - Osteoarthritis causes changes in the subchondral bone structure and composition. Plain radiography is a cheap, fast, and widely available imaging method. Bone tissue can be well seen from plain radiograph, which however is only a 2D projection of the actual 3D structure. Therefore, the aim was to investigate the relationship between bone density- and structure-related parameters from 2D plain radiograph and 3D bone parameters assessed from micro computed tomography (uCT) ex vivo. Right tibiae from eleven cadavers without any diagnosed joint disease were imaged using radiography and with uCT. Bone density- and structure-related parameters were calculated from four different locations from the radiographs of proximal tibia and compared with the volumetric bone microarchitecture from the corresponding regions. Bone density from the plain radiograph was significantly related with the bone volume fraction (r = 0.86; n = 44; p < 0.01). Mean homogeneity index for orientation of local binary patterns (HI(angle,mean)) and fractal dimension of vertical structures (FD(Ver)) were related (p < 0.01) with connectivity density (HI(angle,mean): r = -0.73, FD(Ver): r = 0.69) and trabecular separation (HI(angle,mean): r = 0.73, FD(Ver): r = -0.70) when all ROIs were pooled together (n = 44). Bone density and structure in tibia from standard clinically available 2D radiographs are significantly correlated with true 3D microstructure of bone. PMID- 26369639 TI - Nucleotide and phylogenetic analysis of human papillomavirus type 11 isolated from juvenile-onset recurrent respiratory papillomatosis in China. AB - To assess the association between sequence variants of human papillomavirus (HPV) 11 and recurrent respiratory papillomatosis and the taxonomy and evolutionary history of HPV 11. Complete HPV 11 nucleotide sequences were sequenced by Illumina HiSeq2000 Analyzers and compared with the HPV 11 prototype isolate (GenBank accession number: M14119) using Blast 2.0 server software. Eighteen full length HPV 11 genomic sequences were amplified and sequenced. A total of 49 nucleotide mutations were identified, 12 of which resulted in amino acid changes. HPV 11 variants were highly conserved; the maximum pairwise difference was approximately 0.49%. The maximum pairwise difference of the 18 variants in our research was 0.39%. HPV 11 is less polymorphic than the majority of studied HPV genotypes. PMID- 26369640 TI - Radiotherapy for benign achillodynia. Long-term results of the Erlangen Dose Optimization Trial. AB - BACKGROUND: The aim of this study was to evaluate the long-term efficacy of two dose-fractionation schedules for radiotherapy of achillodynia. PATIENTS AND METHODS: Between February 2006 and February 2010, 112 evaluable patients were recruited for this prospective trial. All patients received orthovoltage radiotherapy. One course consisted of 6 fractions/3 weeks. In the case of insufficient remission of pain after 6 weeks, a second series was performed. Patients were randomly assigned to receive either single doses of 0.5 or 1.0 Gy. The endpoint was pain reduction. Pain was measured before, right after (early response), 6 weeks after (delayed response), and approximately 2 years after radiotherapy (long-term response) with a questionnaire-based visual analogue scale (VAS) and a comprehensive pain score (CPS). RESULTS: The median follow-up was 24 months (range, 11-56). The overall early, delayed, and long-term response rates for all patients were 84 %, 88 %, and 95 %, respectively. The mean VAS values before treatment for early, delayed, and long-term responses for the 0.5 Gy and 1.0-Gy groups were 55.7 +/- 21.0 and 58.2 +/- 23.5 (p = 0.53), 38.0 +/- 23.2 and 30.4 +/- 22.6 (p = 0.08), 35.5 +/- 25.9 and 30.9 +/- 25.4 (p = 0.52), and 11.2 +/- 16.4 and 15.3 +/- 18.9 (p = 0.16), respectively. The mean CPS values before treatment for early, delayed, and long-term responses were 8.2 +/- 3.0 and 8.9 +/- 3.3 (p = 0.24), 5.6 +/- 3.1 and 5.4 +/- 3.3 (p = 0.76), 4.4 +/- 2.6 and 5.3 +/- 3.8 (p = 0.58), and 2.2 +/- 2.9 and 2.8 +/- 3.3 (p = 0.51), respectively. No significant differences in long-term response quality between the two arms was found (p = 0.73). CONCLUSION: Radiotherapy is a very effective treatment for the management of benign achillodynia. For radiation protection, the dose for a radiotherapy series should not exceed 3.0 Gy. PMID- 26369641 TI - [Radiation Therapy to the Plexus Brachialis in Breast Cancer Patients: Analysis of Paresthesia in Relation to Dose and Volume]. PMID- 26369642 TI - Computed tomography segmental calcium score (SCS) to predict stenosis severity of calcified coronary lesions. AB - To estimate the probability of >= 50% coronary stenoses based on computed tomography (CT) segmental calcium score (SCS) and clinical factors. The Institutional Review Board approved the study. A training sample of 201 patients underwent CT calcium scoring and conventional coronary angiography (CCA). All patients consented to undergo CT before CCA after being informed of the additional radiation dose. SCS and calcification morphology were assessed in individual coronary segments. We explored the predictive value of patient's symptoms, clinical history, SCS and calcification morphology. We developed a prediction model in the training sample based on these variables then tested it in an independent test sample. The odds ratio (OR) for >= 50% coronary stenosis was 1.8-fold greater (p = 0.006) in patients with typical chest pain, twofold (p = 0.014) greater in patients with acute coronary syndromes, twofold greater (p < 0.001) in patients with prior myocardial infarction. Spotty calcifications had an OR for >= 50% stenosis 2.3-fold (p < 0.001) greater than the absence of calcifications, wide calcifications 2.7-fold (p < 0.001) greater, diffuse calcifications 4.6-fold (p < 0.001) greater. In middle segments, each unit of SCS had an OR 1.2-fold (p < 0.001) greater than in distal segments; in proximal segments the OR was 1.1-fold greater (p = 0.021). The ROC curve area of the prediction model was 0.795 (0.95 confidence interval 0.602-0.843). Validation in a test sample of 201 independent patients showed consistent diagnostic performance. In conjunction with calcification morphology, anatomical location, patient's symptoms and clinical history, SCS can be helpful to estimate the probability of >= 50% coronary stenosis. PMID- 26369643 TI - Molecular Characterization and In Vitro Antifungal Susceptibility of 316 Clinical Isolates of Dermatophytes in Iran. AB - Dermatophytosis is a common mycotic infection of the skin, nail, and hair, associated with major public health concern worldwide. Various species of dermatophytes show significant differences in susceptibility to antifungals. Here, we present the antifungal susceptibility of a large collection of molecularly identified dermatophyte isolates obtained from tropical region of south of Iran. A total of 9485 patients clinically suspected to have cutaneous fungal infections were examined. Dermatophytosis was confirmed in 1502 cases by direct microscopy and culture. Three hundred and sixteen isolates recovered in culture were identified to species level using PCR sequencing of ITS region and RFLP. Tinea corporis was the most prevalent type of clinical manifestation (35.2 %), followed by tinea cruris (17 %), tinea capitis (12.8 %), tinea pedis (11.3 %), tinea manuum (11 %), tinea unguium (6.9 %), and tinea barbae (5.8 %). Trichophyton interdigitale was the most common isolate (49.36 %), followed by Trichophyton rubrum (18.98 %), Epidermophyton floccosum (13.29 %), Microsporum canis (9.17 %), Arthroderma benhamiae (T. anamorph of A. benhamiae; 5.38 %), and Trichophyton tonsurans (3.79 %). Overall, irrespective of the geographical region, terbinafine was the most potent antifungal against all isolates, with an MIC range of 0.002-0.25 MUg/mL, followed by itraconazole (0.004-0.5 MUg/mL), griseofulvin (0.125-8 MUg/mL), and fluconazole (4-128 MUg/mL). Analysis of our data revealed a significant increase in the frequency of A.benhamiae, which definitely warrants further investigation to explore source of this infection in south of Iran. Moreover, terbinafine was the most effective antifungal against all isolates, in vitro. PMID- 26369644 TI - Rhodotorula mucilaginosa Fungemia and Pleural Tuberculosis in an Immunocompetent Patient: An Uncommon Association. AB - We report an atypical case of Rhodotorula mucilaginosa fungemia coexisting with pleural tuberculosis, in an immunocompetent host. The patient was an inhaled drug abuser and worked in a fruit market. The diagnosis of Rhodotorula mucilaginosa infection was established by the isolation of the yeast in two blood cultures followed by a good response to amphotericin B treatment. Persistent evening fever and pleural effusion led to the second diagnosis-pleural tuberculosis. In the last 5 years, this was the only case of Rhodotorula mucilaginosa fungemia in our hospital and the first case in the literature that documents Rhodotorula mucilaginosa fungemia associated with pleural tuberculosis. PMID- 26369645 TI - Successful endoscopic stent placement as a bridge to surgery for colonic obstruction induced by bevacizumab-based chemotherapy. AB - The use of a self-expandable metallic stent (SEMS) as a bridge to surgery (BTS) for obstructive colorectal cancer is known to be effective. However, whether the use of a SEMS as a BTS for obstruction induced by effective chemotherapy (CTx) is useful is unknown. We present the case of a 54-year-old female patient with colorectal cancer who underwent SEMS placement as a BTS for colorectal obstruction induced by bevacizumab-based CTx. The patient was diagnosed as having transverse colon cancer with multiple liver metastases invading the inferior vena cava. Bevacizumab-based CTx was started; however, although it was effective, colonic obstruction occurred at the primary site after 31 months. A SEMS was placed as a BTS, and surgical resection of the primary lesion was performed after cessation of bevacizumab. However, the liver metastases remained unresectable. CTx was restarted after surgery, and 48-month survival was achieved. This case shows that SEMS placement as a BTS for colorectal obstruction induced by a good response to bevacizumab-based CTx was safe and beneficial. With the development of CTx and molecular-targeted agents, the frequency of colorectal obstruction associated with effective CTx is expected to increase. SEMS placement as a BTS might be one of the treatment options. PMID- 26369646 TI - Early occurrence of influenza A epidemics coincided with changes in occurrence of other respiratory virus infections. AB - BACKGROUND: Viral interaction in which outbreaks of influenza and other common respiratory viruses might affect each other has been postulated by several short studies. Regarding longer time periods, influenza epidemics occasionally occur very early in the season, as during the 2009 pandemic. Whether early occurrence of influenza epidemics impacts outbreaks of other common seasonal viruses is not clear. OBJECTIVES: We investigated whether early occurrence of influenza outbreaks coincides with shifts in the occurrence of other common viruses, including both respiratory and non-respiratory viruses. METHODS: We investigated time trends of and the correlation between positive laboratory diagnoses of eight common viruses in the Netherlands over a 10-year time period (2003-2012): influenza viruses types A and B, respiratory syncytial virus (RSV), rhinovirus, coronavirus, norovirus, enterovirus, and rotavirus. We compared trends in viruses between early and late influenza seasons. RESULTS: Between 2003 and 2012, influenza B, RSV, and coronavirus showed shifts in their occurrence when influenza A epidemics occurred earlier than usual (before week 1). Although shifts were not always consistently of the same type, when influenza type A hit early, RSV outbreaks tended to be delayed, coronavirus outbreaks tended to be intensified, and influenza virus type B tended not to occur at all. Occurrence of rhinovirus, norovirus, rotavirus, and enterovirus did not change. CONCLUSION: When influenza A epidemics occured early, timing of the epidemics of several respiratory winter viruses usually occurring close in time to influenza A was affected, while trends in rhinoviruses (occurring in autumn) and trends in enteral viruses were not. PMID- 26369647 TI - Solid-state fermentation as a potential technique for esterase/lipase production by halophilic archaea. AB - Halophilic archaea are extremophiles, adapted to high-salt environments, showing a big biotechnological potential as enzyme, lipids and pigments producers. Four inert supports (perlite, vermiculite, polyurethane foam and glass fiber) were employed for solid-state fermentation (SSF) of the halophilic archaeon Natronococcus sp. TC6 to investigate biomass and esterase production. A very low esterase activity and high water activity were observed when perlite, vermiculite and polyurethane were used as supports. When glass fiber was employed, an important moisture loss was observed (8.6%). Moreover, moisture retention was improved by mixing polyurethane and glass fiber, resulting in maximal biomass and esterase production. Three halophilic archaea: Natronococcus sp. TC6, Halobacterium sp. NRC-1 and Haloarcula marismortui were cultured by submerged fermentation (SmF) and by SSF; an improvement of 1.3- to 6.2-fold was observed in the biomass and esterase production when SSF was used. Growth was not homogeneous in the mixture, but was predominant in the glass fiber thus was probably because the glass fiber provides a holder to the cells, while the polyurethane acts as an impregnation medium reservoir. To the best of our knowledge, this work is the first report on haloarchaea cultivation by SSF aiming biomass and esterase/lipase activity production. PMID- 26369648 TI - Phylogenetic diversity of nitrogen-utilizing genes in hydrothermal chimneys from 3 middle ocean ridges. AB - Nitrogen-metabolizing genes, including nitrogenase (nifH), periplasmic nitrate reductase (napA), and cytochrome cd 1-type nitrite reductase (nirS), were collected from hydrothermal chimney sulfides on 3 middle ocean ridges and compared for the first time. There was a clear phylogenetic distinction of these nifH genes between different hydrothermal ecosystems, which supported the colonization and potential adaptation by different nitrogen fixing microbes in those sulfides. In particular, in sulfides from low-temperature hydrothermal vents of the Southwest Indian Ocean Ridge, the prevalence of nifH genes appears to be attributed to sulfate-reducing bacteria, suggesting their ecological significance. Phylogenetic analysis of nitrate/nitrite reductase genes indicated that nitrate was a critical electron acceptor for sulfur- or metal-oxidizing bacteria in these hydrothermal ecosystems. Our results provided information about the compositions and diversity of the 3 important genes involved in nitrogen fixation and nitrate/nitrite reduction processes in hydrothermal ecosystems and is the first comprehensive genetic repertoire of genes related to potential nitrogen fixation and denitrification processes in various hydrothermal environments. PMID- 26369650 TI - Mercury and Selenium in Muscle and Target Organs of Scalloped Hammerhead Sharks Sphyrna lewini of the SE Gulf of California: Dietary Intake, Molar Ratios, Loads, and Human Health Risks. AB - Selenium and mercury were evaluated in muscle, liver, kidney, brain, and the stomach contents of juvenile scalloped hammerhead shark Sphyrna lewini. Se:Hg molar ratios were calculated. The average Hg levels in muscle ranged from 0.12 to 1.17 MUg/g (wet weight); Hg was <0.39 MUg/g in liver and kidneys and <0.19 MUg/g in brain. The lowest value of Se was found in muscle (0.4 MUg/g) and the highest in kidney (26.7 MUg/g). An excess of Se over Hg was found, with Se:Hg molar ratios >1. Correlations were found for Hg in muscle with size, age, and weight, and also for Hg in liver with size, age, and weight. Hg in muscle was significantly positive correlated to Hg in brain as well as Hg in liver was correlated to Hg in kidney. The highest Hg in preys was for carangid fishes; scombrid and carangid fishes contributed with the highest Se levels. Results suggest that more than 98 % of the total Hg and 62 % of Se end up in muscle and might be affected by factors, such as geographical area, age, size, and feeding habits. The muscle of S. lewini should be consumed by people cautiously so as not to exceed the recommended intake per week. PMID- 26369649 TI - Exploring the multiple biotechnological potential of halophilic microorganisms isolated from two Argentinean salterns. AB - The biodiversity and biotechnological potential of microbes from central Argentinean halophilic environments have been poorly explored. Salitral Negro and Colorada Grande salterns are neutral hypersaline basins exploded for NaCl extraction. As part of an ecological analysis of these environments, two bacterial and seven archaeal representatives were isolated, identified and examined for their biotechnological potential. The presence of hydrolases (proteases, amylases, lipases, cellulases and nucleases) and bioactive molecules (surfactants and antimicrobial compounds) was screened. While all the isolates exhibited at least one of the tested activities or biocompounds, the species belonging to Haloarcula genus were the most active, also producing antimicrobial compounds against their counterparts. In general, the biosurfactants were more effective against olive oil and aromatic compounds than detergents (SDS or Triton X-100). Our results demonstrate the broad spectrum of activities with biotechnological potential exhibited by the microorganisms inhabiting the Argentinean salterns and reinforce the importance of screening pristine extreme environments to discover interesting/novel bioactive molecules. PMID- 26369651 TI - Impact of the introduction of standardised packaging on smokers' brand awareness and identification in Australia. AB - INTRODUCTION AND AIMS: The introduction of standardised packaging (SP) in Australia in December 2012 has heightened interest in how image and branding might affect smoking. This paper tests the hypothesis that brand awareness and identification among smokers will decline after the introduction of SP. DESIGN AND METHODS: Longitudinal study of three waves of smokers in Australia, conducted between October 2011-February 2012 (pre-SP) (n = 1104), February-May 2013 (post SP1) (n = 1093) and August-December 2014 (post-SP2) (n = 1090). We explored the extent of changes in two variables, brand awareness (noticing others with the brand of cigarettes you smoke) and brand identification (perceiving something in common among smokers of your brand), and examined change in a number of other measures of brand appeal, brand characteristics and determinants of brand choice. RESULTS: Brand awareness 'at least sometimes' reduced from 45.3% pre-SP to 26.9% at post-SP2 [odds ratio (OR) 0.35 (0.27-0.45)]. Brand identification also decreased from 18.2% to 12.7% [OR 0.62 (0.42-0.91)]. Significant decline was also found in measures of perceived brand prestige [OR 0.51 (0.39-0.66)] and choice of brand for health reasons [OR 0.45 (0.32-0.63)]. Liking the look of the pack was strongly associated with brand identification, but only post-SP (P = 0.02 for interaction across the three waves). DISCUSSION AND CONCLUSIONS: The introduction of SP of tobacco products in Australia has been associated with reductions in brand awareness and identification, and changes in related measures. The findings support the notion that SP has reduced the capacity for smokers to use pack branding to create and communicate a desired identity. [Balmford J, Borland R, Yong H-H. Impact of the introduction of standardised packaging on smokers' brand awareness and identification in Australia. Drug Alcohol Rev 2015;00:000-000]. PMID- 26369652 TI - The development and status of Bt rice in China. AB - Multiple lines of transgenic rice expressing insecticidal genes from the bacterium Bacillus thuringiensis (Bt) have been developed in China, posing the prospect of increases in production with decreased application of pesticides. We explore the issues facing adoption of Bt rice for commercial production in China. A body of safety assessment work on Bt rice has shown that Bt rice poses a negligible risk to the environment and that Bt rice products are as safe as non Bt control rice products as food. China has a relatively well-developed regulatory system for risk assessment and management of genetically modified (GM) plants; however, decision-making regarding approval of commercial production has become politicized, and two Bt rice lines that otherwise were ready have not been allowed to enter the Chinese agricultural system. We predict that Chinese farmers would value the prospect of increased yield with decreased use of pesticide and would readily adopt production of Bt rice. That Bt rice lines may not be commercialized in the near future we attribute to social pressures, largely due to the low level of understanding and acceptance of GM crops by Chinese consumers. Hence, enhancing communication of GM crop science-related issues to the public is an important, unmet need. While the dynamics of each issue are particular to China, they typify those in many countries where adoption of GM crops has been not been rapid; hence, the assessment of these dynamics might inform resolution of these issues in other countries. PMID- 26369653 TI - Effects of Liraglutide Monotherapy on Beta Cell Function and Pancreatic Enzymes Compared with Metformin in Japanese Overweight/Obese Patients with Type 2 Diabetes Mellitus: A Subpopulation Analysis of the KIND-LM Randomized Trial. AB - BACKGROUND AND OBJECTIVE: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are becoming one of the major therapeutic options for the treatment of type 2 diabetes mellitus (T2DM). This study was conducted as an exploratory analysis to clarify the effects of liraglutide, a GLP-1RA, on beta cell function, fat distribution and pancreas volume compared with metformin in Japanese overweight/obese patients with T2DM. METHODS: A subpopulation of the Keio study for Initial treatment of type 2 Diabetes with Liraglutide versus Metformin (KIND LM) study participants (n = 20, 10 in oral metformin group and 10 in subcutaneous liraglutide group) who were enrolled at Keio University Hospital and underwent frequently sampled mixed meal tolerance test (MTT) and abdominal computed tomography (CT) at weeks 0 and 24 were included in this analysis. The patients were treated with either metformin or liraglutide throughout the 24-week study period. RESULTS: Changes in glycemic parameters such as glycated hemoglobulin (HbA1c), glycated albumin and 1,5-anhydroglucitol at week 24 were comparable between the groups. An oral minimal model based on MTT revealed that static-phase beta cell responsiveness (Phi s) and static-phase disposition index were significantly increased at week 24 in the liraglutide group but not in the metformin group. There was no significant change in fat distribution as well as body weight at week 24 in either group. Serum amylase and lipase levels modestly but significantly increased in the liraglutide group during the study; however, there was no incidence of pancreatitis and pancreas volume was not changed in the liraglutide group. CONCLUSION: Liraglutide monotherapy for 24 weeks improved beta cell responsiveness with no change in either body weight or fat distribution. Further investigation is needed to clarify the mechanism by which liraglutide increases serum pancreatic enzymes. TRIAL REGISTRATION: The University Hospital Medical Information Network (UMIN) Clinical Trials Registry ( http://www.umin.ac.jp/ctr/ ); UMIN000004243. PMID- 26369654 TI - Assessment of Alcohol-Induced Dose Dumping with a Hydrocodone Bitartrate Extended Release Tablet Formulated with CIMA((r)) Abuse Deterrence Technology. AB - BACKGROUND: Greater drug content requirements for extended-release (ER) opioids necessitate greater protection against dose dumping. Hydrocodone ER employs the CIMA((r)) Abuse-Deterrence Technology platform, which provides resistance against rapid release of the active moiety when the tablet is manipulated or taken with alcohol. OBJECTIVE: Assess effects of alcohol on hydrocodone ER pharmacokinetics. STUDY DESIGN: Open-label, crossover (January 25-April 30, 2010). SETTING: Single center. PARTICIPANTS: Forty healthy adults. INTERVENTION: Subjects received all four treatments in a randomized manner (separated by a minimum 5-day washout): hydrocodone ER 15 mg with 240 mL water and 240 mL orange juice containing 4, 20, and 40% alcohol in a fasted state. Naltrexone was administered to minimize opioid related adverse events. MAIN OUTCOME MEASURE: Effect of alcohol on pharmacokinetics of hydrocodone ER assessed by comparing systemic exposure [maximum plasma drug concentration (Cmax) and area under the plasma drug concentration-versus-time curve from time 0 to infinity (AUC0-infinity)] after administration with alcohol or with water. RESULTS: Geometric means ratios of hydrocodone ER with 4, 20, and 40% alcohol relative to water were 1.05, 1.09, and 1.14, respectively, for Cmax and 1.07, 1.13, and 1.17, respectively, for AUC0 infinity. All 90% confidence intervals for these geometric means ratios fell within the limits of 0.8 and 1.25. Increasing alcohol concentrations did not notably affect systemic exposure but were associated with increased adverse events. CONCLUSIONS: Hydrocodone ER tablets were resistant to dose dumping when administered with alcohol in healthy subjects based on similar systemic exposures observed across all treatments. PMID- 26369655 TI - Effect of Rebamipide on the Premalignant Progression of Chronic Gastritis: A Randomized Controlled Study. AB - BACKGROUND AND OBJECTIVE: Chronic gastritis frequently progresses into precancerous intestinal metaplasia and intraepithelial neoplasia lesions. Rebamipide is a free radical scavenger and we assessed its efficacy on clinical symptoms, gastric mucosal lesions, pathologic grade, and immunohistochemistry in chronic gastritis patients. METHODS: 178 eligible patients were randomized into treatment and control groups. Both groups followed an optimized lifestyle for 26 weeks, but the treatment group was additionally medicated with rebamipide 0.1 g three times per day. Upper gastrointestinal endoscopy was performed in all patients to evaluate the severity of gastritis by the Modified Lanza Scoring (MLS) and histological changes were evaluated by the Updated Sydney System Score (USSS). Gastric mucosa immunohistochemistry in the treatment group was performed using the intestinal metaplasia markers caudal type homeobox transcription factor 2 (CDX2) and trefoil factor 3 (TFF3) detection. RESULTS: There were significant outcome differences between the treatment and control groups regarding the clinical symptom scores (2.62 +/- 1.86 vs. 1.55 +/- 1.61, P = 0.0001), gastric mucosal lesion scores (0.57 +/- 1.05 vs. 0.16 +/- 0.90, P = 0.002), and inflammation (P < 0.05). Only in the treated patients were the rates of intestinal metaplasia (P = 0.017 vs. P = 0.123) and low-grade intraepithelial neoplasia (P = 0.005 vs. P = 0.226) significantly reduced after 26 weeks. The percentages of CDX2 (31.5 vs. 15.7%, P = 0.021) and TFF3 (44.9 vs. 25.8%, P = 0.012) expressing gastric mucosa cells were significantly lower after rebamipide medication than pre-treatment values. CONCLUSIONS: Rebamipide improved the clinical symptoms, gastric mucosal lesions, and pathological grades of chronic gastritis patients and decreased the expression rates of CDX2 and TFF3 in gastric cells. PMID- 26369656 TI - Pharmacokinetic and Pharmacodynamic Comparison of Two Recombinant Human Erythropoietin Formulations, PDA10 and Eprex, in Healthy Korean Male Volunteers: A Randomized, Double-Blinded, Single-Dose, Two-Period Crossover Study. AB - BACKGROUND AND OBJECTIVES: A new biosimilar human recombinant epoetin alfa product (PDA10) has been developed by PanGen Biotech Inc., Korea. This study was planned to demonstrate the pharmacokinetic and pharmacodynamic comparability of PDA10 to an existing epoetin alfa (Eprex) after a single intravenous administration to healthy adult male volunteers. METHODS: A randomized, double blinded, single-dose, crossover study was conducted in 30 subjects. The subjects were assigned randomly to one of two sequence groups, and single doses of 100 IU/kg PDA10 or Eprex were administered intravenously on each of 2 treatment days separated by a 4-week washout period. Plasma erythropoietin concentrations were measured using an enzyme-linked immunosorbent assay and the pharmacokinetic parameters of the two treatments were compared. The time course and area under the effect curve (AUEC) of absolute reticulocyte counts were used as surrogate parameters for the pharmacodynamic evaluation. Adverse events (AEs) were recorded. RESULTS: A total of 30 subjects were enrolled, and 27 completed the study. The geometric mean ratios (PDA10/Eprex) of erythropoietin for maximum plasma concentration (C max) and area under the plasma concentration-time curve to the last measurable concentration (AUC0-last) after intravenous administration of 100 IU/kg were 1.00 (90% confidence interval [CI] 0.96-1.05) and 0.96 (90% CI 0.93-1.00). The absolute reticulocyte counts of PDA10 and Eprex were similar, as determined from the maximum reticulocyte count and AUEC0-last values. Treatment emergent AEs were mild and occurred in seven subjects. CONCLUSION: PDA10 and Eprex met the regulatory criteria for bioequivalence with respect to their pharmacokinetic profiles and pharmacodynamic actions. PMID- 26369657 TI - The Effects of Transition from Bedtime to Morning Glargine Administration in Patients with Poorly Regulated Type 1 Diabetes Mellitus: Croatian Pilot Study. AB - INTRODUCTION: The objective of this study was to compare differences in glucoregulation, frequency of hypoglycemic episodes, glucose variability and lipid profiles of inpatients with poorly regulated type 1 diabetes mellitus (T1DM) after evening versus morning glargine application. METHODS: Eighteen patients with poorly regulated T1DM, glycated hemoglobin (Hba1c) levels >=7% and frequent nocturnal and/or morning hypoglycemic episodes were included in this study. There was a 12-week screening phase where patients continued their usual insulin regimen and were encouraged to achieve optimal glycemic control; however, all patients maintained HbA1c values >=7% and continued to have frequent nocturnal and/or morning hypoglycemic events and were therefore transitioned to morning application of insulin glargine for 12 weeks. The primary outcome was to investigate changes in HbA1c values 12 weeks after the transition. The secondary outcome was to evaluate the effect of transition on glucose variability, incidence of hypoglycemic episodes, insulin doses, lipid profile and weight. Data were analyzed using paired Student's t test and Pearson correlation. RESULTS: After the transition, there was no significant change in total daily dose of basal insulin (p 0.114) and the average body weight remained unchanged, while significant reduction of HbA1c was present (8.02 +/- 0.5 vs. 7.4 +/- 0.3%) (p < 0.01) resulting in a decrease in nocturnal and daytime hypoglycemic episodes per month per person (p < 0.01). Parameters of glucose variability (glycemic standard deviations and J-index) were also improved after transition period (p < 0.01). As for the lipid profile, increase of high-density lipoprotein cholesterol and decrease of triglycerides (p < 0.01) were noticed, while other lipid parameters remained unaffected. Furthermore, insignificant association of basal insulin dose with HbA1c values regardless of the time of administration was observed. CONCLUSION: In patients with poorly regulated T1DM, transition to morning application of glargine improved glucoregulation (including a decrease in HbA1c, glucose variability and number of nocturnal hypoglycemic episodes), followed by favorable changes in lipid profile without affecting body weight. These effects were associated with the time of application, but not with the insulin dose. PMID- 26369658 TI - Is Teaching Simple Surgical Skills Using an Operant Learning Program More Effective Than Teaching by Demonstration? AB - BACKGROUND: A surgical procedure is a complex behavior that can be constructed from foundation or component behaviors. Both the component and the composite behaviors built from them are much more likely to recur if it they are reinforced (operant learning). Behaviors in humans have been successfully reinforced using the acoustic stimulus from a mechanical clicker, where the clicker serves as a conditioned reinforcer that communicates in a way that is language- and judgment free; however, to our knowledge, the use of operant-learning principles has not been formally evaluated for acquisition of surgical skills. QUESTIONS/PURPOSES: Two surgical tasks were taught and compared using two teaching strategies: (1) an operant learning methodology using a conditioned, acoustic reinforcer (a clicker) for positive reinforcement; and (2) a more classical approach using demonstration alone. Our goal was to determine whether a group that is taught a surgical skill using an operant learning procedure would more precisely perform that skill than a group that is taught by demonstration alone. METHODS: Two specific behaviors, "tying the locking, sliding knot" and "making a low-angle drill hole," were taught to the 2014 Postgraduate Year (PGY)-1 class and first- and second-year medical students, using an operant learning procedure incorporating precise scripts along with acoustic feedback. The control groups, composed of PGY-1 and 2 nonorthopaedic surgical residents and first- and second-year medical students, were taught using demonstration alone. The precision and speed of each behavior was recorded for each individual by a single experienced surgeon, skilled in operant learning. The groups were then compared. RESULTS: The operant learning group achieved better precision tying the locking, sliding knot than did the control group. Twelve of the 12 test group learners tied the knot and precisely performed all six component steps, whereas only four of the 12 control group learners tied the knot and correctly performed all six component steps (the test group median was 10 [range, 10-10], the control group median was 0 [range, 0-10], p = 0.004). However, the median "time to tie the first knot" for the test group was longer than for the control group (test group median 271 seconds [range, 184 626 seconds], control group median 163 seconds [range 93-900 seconds], p = 0.017), whereas the "time to tie 10 of the locking, sliding knots" was the same for both groups (test group mean 95 seconds +/- SD = 15 [range, 67-120 seconds], control group mean 95 seconds +/- SD = 28 [range, 62-139 seconds], p = 0.996). For the low-angle drill hole test, the test group more consistently achieved the ideal six-step behavior for precisely drilling the low-angle hole compared with the control group (p = 0.006 for the median number of technique success comparison with an odds ratio [at the 95% confidence interval] of 82.3 [29.1 232.8]). The mean time to drill 10 low-angle holes was not different between the test group (mean 193 seconds +/- SD = 26 [range, 153-222 seconds]) and the control group (mean 146 seconds +/- SD = 63 [range, 114-294 seconds]) (p = 0.084). CONCLUSIONS: Operant learning occurs as the behavior is constructed and is highly reinforced with the result measured, not in the time saved, but in the ultimate outcome of an accurately built complex behavior. LEVEL OF EVIDENCE: Level II, therapeutic study. PMID- 26369659 TI - Retraction Note to: Candidate gene prioritization. PMID- 26369660 TI - Comparison of magnetic wire navigation with the conventional wire technique for percutaneous coronary intervention of chronic total occlusions: a randomised, controlled study. AB - Wire crossing of a chronic total coronary occlusion (CTO) is time consuming and limited by the amount of contrast agent and time of radiation exposure. Magnetic wire navigation (MWN) might accelerate wire crossing by maintaining a coaxial vessel orientation. This study compares MWN with the conventional approach for recanalization of CTOs. Forty symptomatic patients with CTO were randomised to MWN (n = 20) or conventional approach (n = 20) for antegrade crossing of the occlusion. In the intention-to-treat analysis, MWN showed a shorter crossing time (412 versus 1131 s; p = 0.001), and, consequently, lower usage of contrast agent (primary endpoint 42 versus 116 ml; p = 0.01), and lower radiation exposure (dose area product: 29 versus 80 Gy*cm(2); p = 0.002) during wire crossing compared to the conventional approach. Accordingly, in the per-protocol analysis, the wire crossing rate was, in trend, higher using the conventional approach (17 of 31) compared to MWN (9 of 28; p = 0.08). The use of MWN for revascularisation of CTOs is feasible and reduces crossing time, use of contrast agent, and radiation exposure. However, due to a broader selection of wires, the conventional approach enables wire crossing in cases failed by MWN and seems to be the more successful choice. PMID- 26369661 TI - The use of Amerindian charm plants in the Guianas. AB - BACKGROUND: Magical charm plants to ensure good luck in hunting, fishing, agriculture, love and warfare are known among many Amerindians groups in the Guianas. Documented by anthropologists as social and political markers and exchangeable commodities, these charms have received little attention by ethnobotanists, as they are surrounded by secrecy and are difficult to identify. We compared the use of charm species among indigenous groups in the Guianas to see whether similarity in charm species was related to geographical or cultural proximity. We hypothesized that cultivated plants were more widely shared than wild ones and that charms with underground bulbs were more widely used than those without such organs, as vegetatively propagated plants would facilitate transfer of charm knowledge. METHODS: We compiled a list of charm plants from recent fieldwork and supplemented these with information from herbarium collections, historic and recent literature among 11 ethnic groups in the Guianas. To assess similarity in plant use among these groups, we performed a Detrended Component Analysis (DCA) on species level. To see whether cultivated plants or vegetatively propagated species were more widely shared among ethnic groups than wild species or plants without rhizomes, tubers or stem-rooting capacity, we used an independent sample t-test. RESULTS: We recorded 366 charms, representing 145 species. The majority were hunting charms, wild plants, propagated via underground bulbs and grown in villages. Our data suggest that similarity in charm species is associated with geographical proximity and not cultural relatedness. The most widely shared species, used by all Amerindian groups, is Caladium bicolor. The tubers of this plant facilitate easy transport and its natural variability allows for associations with a diversity of game animals. Human selection on shape, size and color of plants through clonal reproduction has ensured the continuity of morphological traits and their correlation with animal features. CONCLUSIONS: Charm plants serve as vehicles for traditional knowledge on animal behavior, tribal warfare and other aspects of oral history and should therefore deserve more scientific and societal attention, especially because there are indications that traditional knowledge on charms is disappearing. PMID- 26369662 TI - Daily estimation of the severity of organ dysfunctions in critically ill children by using the PELOD-2 score. AB - INTRODUCTION: Daily or serial evaluation of multiple organ dysfunction syndrome (MODS) scores may provide useful information. We aimed to validate the daily (d) PELOD-2 score using the set of seven days proposed with the previous version of the score. METHODS: In all consecutive patients admitted to nine pediatric intensive care units (PICUs) we prospectively measured the dPELOD-2 score at day 1, 2, 5, 8, 12, 16, and 18. PICU mortality was used as the outcome dependent variable. The discriminant power of the dPELOD-2 scores was estimated using the area under the ROC curve and the calibration using the Hosmer-Lemeshow chi-square test. We used a logistic regression to investigate the relationship between the dPELOD-2 scores and outcome, and between the change in PELOD-2 score from day 1 and outcome. RESULTS: We included 3669 patients (median age 15.5 months, mortality rate 6.1%, median length of PICU stay 3 days). Median dPELOD-2 scores were significantly higher in nonsurvivors than in survivors (p < 0.0001). The dPELOD-2 score was available at least at day 2 in 2057 patients: among the 796 patients without MODS on day 1, 186 (23.3%) acquired the syndrome during their PICU stay (mortality 4.9% vs. 0.3% among the 610 who did not; p < 0.0001). Among the 1261 patients with MODS on day 1, the syndrome worsened in 157 (12.4%) and remained unchanged or improved in 1104 (87.6%) (mortality 22.9% vs. 6.6%; p < 0.0001). The AUC of the dPELOD-2 scores ranged from 0.75 (95% CI: 0.67-0.83) to 0.89 (95% CI: 0.86-0.91). The calibration was good with a chi-square test between 13.5 (p = 0.06) and 0.9 (p = 0.99). The PELOD-2 score on day 1 was a significant prognostic factor; the serial evaluation of the change in the dPELOD-2 score from day1, adjusted for baseline value, demonstrated a significant odds ratio of death for each of the 7 days. CONCLUSION: This study suggests that the progression of the severity of organ dysfunctions can be evaluated by measuring the dPELOD-2 score during a set of 7 days in PICU, providing useful information on outcome in critically ill children. Its external validation would be useful. PMID- 26369663 TI - "Once the government employs you, it forgets you": Health workers' and managers' perspectives on factors influencing working conditions for provision of maternal health care services in a rural district of Tanzania. AB - BACKGROUND: In many developing countries, health workforce crisis is one of the predominant challenges affecting the health care systems' function of providing quality services, including maternal care. The challenge is related to how these countries establish conducive working conditions that attract and retain health workers into the health care sector and enable them to perform effectively and efficiently to improve health services particularly in rural settings. This study explored the perspectives of health workers and managers on factors influencing working conditions for providing maternal health care services in rural Tanzania. The researchers took a broad approach to understand the status of the current working conditions through a governance lens and brought into context the role of government and its decentralized organs in handling health workers in order to improve their performance and retention. METHODS: In-depth interviews were conducted with 22 informants (15 health workers, 5 members of Council Health Management Team and 2 informants from the District Executive Director's office). An interview guide was used with questions pertaining to informants' perspective on provision of maternal health care service, working environment, living conditions, handling of staff's financial claims, avenue for sharing concerns, opportunities for training and career progression. Probing questions on how these issues affect the health workers' role of providing maternal health care were employed. Document reviews and observations of health facilities were conducted to supplement the data. The interviews were analysed using a qualitative content analysis approach. RESULTS: Overall, health workers felt abandoned and lost within an unsupportive system they serve. Difficult working and living environments that affect health workers' role of providing maternal health care services were dominant concerns raised from interviews with both health workers and managers. Existence of a bureaucratic and irresponsible administrative system was reported to result in the delay in responding to the health workers' claims timely and that there is no transparency and fairness in dealing with health workers' financial claims. Informants also reported on the non-existence of a formal motivation scheme and a free avenue for voicing and sharing health workers' concerns. Other challenges reported were lack of a clear strategic plan for staff career advancement and continuous professional development to improve health workers' knowledge and skills necessary for providing quality maternal health care. CONCLUSION: Health workers working in rural areas are facing a number of challenges that affect their working conditions and hence their overall performance. The government and its decentralized organs should be accountable to create conducive working and living environments, respond to health workers' financial claims fairly and equitably, plan for their career advancement and create a free avenue for voicing and sharing concerns with the management. To achieve this, efforts should be directed towards improving the governance of the human resource management system that will take into account the stewardship role of the government in handling human resource carefully and responsibly. PMID- 26369664 TI - Virologic suppression and mortality of patients who migrate for HIV care in the province of British Columbia, Canada, from 2003 to 2012: a retrospective cohort study. AB - BACKGROUND: Migration among persons living with HIV (PLWH) seeking HIV care is common; however its effect on health outcomes in resource-rich settings is not well understood. We conducted a retrospective cohort study to quantify the extent to which PLWH are migrating for care within British Columbia (BC) and its association with virologic suppression and mortality. METHODS: Eligible PLWH first initiated treatment in BC between 2003 and 2012 (N = 3653). Analyses were performed at the regional Health Authority (HA) level (N = 5). For privacy reasons, we kept the name of these HAs anonymous and we re-named these five regions as 1 to 5. PLWH were classified according to the HA where they resided and received HIV care. We calculated all-cause mortality rates, life expectancies (at age of 20 years), and in, out and net migration rates across HAs using different demographic methods. Virologic suppression (<50 copies/mL) was based on the last viral load available for each PLWH. We also calculated per-capita rates (per 100 PLWH ever on cART) for each HA by dividing the number of PLWH by the number of physicians attending this population. RESULTS: There is considerable heterogeneity in physician availability across all HAs, with per-capita rates (per 100 PLWH ever on cART) ranging from 2.2 (HA 1) to 12.7 (HA 3) based on the HA PLWH received care. We observed that in HAs 1, 4, and 5, between 4 and 10% of PLWH migrated to HA 3 (i.e. the largest urban center) to receive care, and for HA 2 this proportion increased to 21%. In HA 3, 77% of its PLWH residents remained in the same HA for their care. Migrating to a larger center for HIV care was not associated with higher rates of viral load suppression; it was significantly associated with lower mortality rates and higher life expectancies. CONCLUSIONS: A thorough understanding of the reason(s) for these significant migration rates across BC will be critical to inform resource allocation and optimize the impact of HIV treatment. PMID- 26369666 TI - The codon-optimized Delta(6)-desaturase gene of Pythium sp. as an empowering tool for engineering n3/n6 polyunsaturated fatty acid biosynthesis. AB - BACKGROUND: The ?(6)-desaturase gene, encoding a key enzyme in the biosynthesis of polyunsaturated fatty acids, has potential in pharmaceutical and nutraceutical applications. RESULTS: The ?(6)-desaturase gene has been isolated from a selected strain of Oomycetes, Pythium sp. BCC53698. The cloned gene (PyDes6) contained an open reading frame (ORF) of 1401 bp encoding 466 amino acid residues. The deduced amino acid sequence shared a high similarity to those of other ?(6)-desaturases that contained the signature features of a membrane-bound ?(6)-desaturase, including a cytochrome b 5 and three histidine-rich motifs and membrane-spanning regions. Heterologous expression in Saccharomyces cerevisiae showed that monoene, diene and triene fatty acids having ?(9)-double bond were substrates for PyDes6. No distinct preference between the n-3 and n-6 polyunsaturated fatty acyl substrates was found. The ?(6)-desaturated products were markedly increased by codon optimization of PyDes6. CONCLUSION: The codon-optimized ?(6)-desaturase gene generated in this study is a promising tool for further reconstitution of the fatty acid profile, in a host system of choice, for the production of economically important fatty acids, particularly the n-3 and n-6 polyunsaturated fatty acids. PMID- 26369665 TI - Identification of four functionally important microRNA families with contrasting differential expression profiles between drought-tolerant and susceptible rice leaf at vegetative stage. AB - BACKGROUND: Developing drought-tolerant rice varieties with higher yield under water stressed conditions provides a viable solution to serious yield-reduction impact of drought. Understanding the molecular regulation of this polygenic trait is crucial for the eventual success of rice molecular breeding programmes. microRNAs have received tremendous attention recently due to its importance in negative regulation. In plants, apart from regulating developmental and physiological processes, microRNAs have also been associated with different biotic and abiotic stresses. Hence here we chose to analyze the differential expression profiles of microRNAs in three drought treated rice varieties: Vandana (drought-tolerant), Aday Sel (drought-tolerant) and IR64 (drought-susceptible) in greenhouse conditions via high-throughput sequencing. RESULTS: Twenty-six novel microRNA candidates involved in the regulation of diverse biological processes were identified based on the detection of miRNA*. Out of their 110 predicted targets, we confirmed 16 targets from 5 novel microRNA candidates. In the differential expression analysis, mature microRNA members from 49 families of known Oryza sativa microRNA were differentially expressed in leaf and stem respectively with over 28 families having at least a similar mature microRNA member commonly found to be differentially expressed between both tissues. Via the sequence profiling data of leaf samples, we identified osa-miR397a/b, osa miR398b, osa-miR408-5p and osa-miR528-5p as being down-regulated in two drought tolerant rice varieties and up-regulated in the drought-susceptible variety. These microRNAs are known to be involved in regulating starch metabolism, antioxidant defence, respiration and photosynthesis. A wide range of biological processes were found to be regulated by the target genes of all the identified differentially expressed microRNAs between both tissues, namely root development (5.3-5.7 %), cell transport (13.2-18.4 %), response to stress (10.5-11.3 %), lignin catabolic process (3.8-5.3 %), metabolic processes (32.1-39.5 %), oxidation-reduction process (9.4-13.2 %) and DNA replication (5.7-7.9 %). The predicted target genes of osa-miR166e-3p, osa-miR166h-5p*, osa-miR169r-3p* and osa-miR397a/b were found to be annotated to several of the aforementioned biological processes. CONCLUSIONS: The experimental design of this study, which features rice varieties with different drought tolerance and tissue specificity (leaf and stem), has provided new microRNA profiling information. The potentially regulatory importance of the microRNA genes mentioned above and their target genes would require further functional analyses. PMID- 26369667 TI - Fragile X syndrome: economic burden and health-related quality of life of patients and caregivers in France. AB - BACKGROUND: Fragile X syndrome (FXS) is the main hereditary cause of intellectual disability. Although the associated burden appears to be considerable, to date no study has comprehensively assessed the cost incurred because of FXS, including its specific impact on health-related quality of life and the burden on caregivers using standardised quantitative tools. The aim of this article is to provide data in order to increase awareness of the repercussions of FXS on patients and caregivers as well as on the health and social care systems in France. METHODS: A retrospective cross-sectional study was carried out on 145 patients recruited through Le Goeland X-Fragile and Mosaiques, the French FXS patient associations. Data on their demographic characteristics and resource use were obtained from an online questionnaire, and costs were estimated by a bottom up approach. The EQ-5D health questionnaire was used to measure patients' and caregivers' health-related quality of life. Perceived burden of care was measured using the Zarit Caregiver Burden Interview. The Barthel index, a non-utility based assessment, was used to measure patients' level of dependence. RESULTS: The annual total direct cost of FXS was estimated at ?25 800 per patient. The main contributors were informal care provided by the main caregiver (?10 500) and social services (?8400). Healthcare costs, estimated at ?2700, represented only a minor share. Mean EQ-5D utility scores were 0.49 for patients and 0.75 for caregivers. The mean burden for caregivers as measured by the Zarit Caregiver Burden Interview was 39.9. CONCLUSIONS: Fragile X syndrome requires significant resources that are mainly of a non-medical nature and are higher for children than for adults. Compared with related diseases, it constitutes a particularly high burden for caregivers. Using a bottom-up approach and a wide range of standardised measures, this study underscores the need for greater awareness of the burden of FXS as well as an assessment of new and existing interventions to address it. PMID- 26369669 TI - The complete mitochondrial genome of the Fossorochromis rostratus. AB - The Fossorochromis rostratus is a species of cichlid endemic to Lake Malawi in East Africa. In this study, we first reported the complete mitochondrial genome of F. rostratus. The whole mitochondrial genome is 16 581 bp in length, which contains 13 protein-coding genes, 22 transfer RNA genes, and two ribosomal RNA genes. The GC content of this mitochondrial genome is 45.96% (27.47% A, 26.57%T, 30.12% C, and 15.84% G), similar to Astatotilapia calliptera (the GC content of 45.90%). We constructed a phylogenetic tree on the complete mitochondrial genomes of these two species and other 10 closely related species to show their phylogenic relationship. The complete mitochondrial genome of F. rostratus and its phylogenic relationship with other related species would facilitate our understanding of the evolution of Cichlidae mitochondrial genome. PMID- 26369668 TI - Leg and Trunk Impairments Predict Participation in Life Roles in Older Adults: Results From Boston RISE. AB - BACKGROUND: The physical impairments that affect participation in life roles among older adults have not been identified. Using the International Classification of Functioning Disability and Health as a conceptual framework, we aimed to determine the leg and trunk impairments that predict participation over 2 years, both directly and indirectly through mediation by changes in activities. METHODS: We analyzed 2 years of data from the Boston Rehabilitative Impairment Study of the Elderly, a cohort study of 430 primary care patients with self reported mobility limitation (mean age 77 years; 68% female; average of four chronic conditions). Frequency of and limitations in participation were examined using the Late-Life Disability Instrument. Baseline physical impairments included: leg strength, leg speed of movement, knee range of motion (ROM), ankle ROM, leg strength asymmetry, kyphosis, and trunk extensor endurance. Structural equation modeling with latent growth curve analysis was used to identify the impairments that predicted participation at year 2, mediated by changes in activities. Models were adjusted for baseline participation, age, and gender. RESULTS: Leg speed and ankle ROM directly influenced participation in life roles during follow-up (betadirect = 1.39-4.53 and 4.70, respectively). Additionally, ankle ROM and trunk extensor endurance contributed indirectly to participation score at follow-up via effects on changes in activities (betaindirect = -1.06 to 4.24 and 1.01 to 4.18, respectively). CONCLUSIONS: Leg speed, ankle ROM, and trunk extensor endurance are key physical impairments predicting participation in life roles in older adults. These results have implications for the development of exercise interventions to enhance participation. PMID- 26369670 TI - The Evolutionary Dynamics of Stochastic Epidemic Model with Nonlinear Incidence Rate. AB - A stochastic SIRS epidemic model with nonlinear incidence rate and varying population size is formulated to investigate the effect of stochastic environmental variability on inter-pandemic transmission dynamics of influenza A. Sufficient conditions for extinction and persistence of the disease are established. In the case of persistence, the existence of endemic stationary distribution is proved and the distance between stochastic solutions and the endemic equilibrium of the corresponding deterministic system in the time mean sense is estimated. Based on realistic parameters of influenza A in humans, numerical simulations have been performed to verify/extend our analytical results. It is found that: (i) the deterministic threshold of the influenza A extinction R(S)0 may exist and the threshold parameter will be overestimated in case of neglecting the impaction of environmental noises; (ii) the presence of environmental noises is capable of supporting the irregular recurrence of influenza epidemic, and the average level of the number of infected individuals I(t) always decreases with the increase in noise intensity; and (iii) if R(S)0 > 1, the volatility of I(t) increases with the increase of noise intensity, while the volatility of I(t) decreases with the increase in noise intensity if R(S)0 < 1. PMID- 26369671 TI - Massive integration of diverse protein quality assessment methods to improve template based modeling in CASP11. AB - Model evaluation and selection is an important step and a big challenge in template-based protein structure prediction. Individual model quality assessment methods designed for recognizing some specific properties of protein structures often fail to consistently select good models from a model pool because of their limitations. Therefore, combining multiple complimentary quality assessment methods is useful for improving model ranking and consequently tertiary structure prediction. Here, we report the performance and analysis of our human tertiary structure predictor (MULTICOM) based on the massive integration of 14 diverse complementary quality assessment methods that was successfully benchmarked in the 11th Critical Assessment of Techniques of Protein Structure prediction (CASP11). The predictions of MULTICOM for 39 template-based domains were rigorously assessed by six scoring metrics covering global topology of Calpha trace, local all-atom fitness, side chain quality, and physical reasonableness of the model. The results show that the massive integration of complementary, diverse single model and multi-model quality assessment methods can effectively leverage the strength of single-model methods in distinguishing quality variation among similar good models and the advantage of multi-model quality assessment methods of identifying reasonable average-quality models. The overall excellent performance of the MULTICOM predictor demonstrates that integrating a large number of model quality assessment methods in conjunction with model clustering is a useful approach to improve the accuracy, diversity, and consequently robustness of template-based protein structure prediction. Proteins 2016; 84(Suppl 1):247-259. (c) 2015 Wiley Periodicals, Inc. PMID- 26369672 TI - Feasibility of neurally adjusted positive end-expiratory pressure in rabbits with early experimental lung injury. AB - BACKGROUND: During conventional Neurally Adjusted Ventilatory Assist (NAVA), the electrical activity of the diaphragm (EAdi) is used for triggering and cycling off inspiratory assist, with a fixed PEEP (so called "Triggered Neurally Adjusted Ventilatory Assist" or "tNAVA"). However, significant post-inspiratory activity of the diaphragm can occur, believed to play a role in maintaining end-expiratory lung volume. Adjusting pressure continuously, in proportion to both inspiratory and expiratory EAdi (Continuous NAVA, or cNAVA), would not only offer inspiratory assist for tidal breathing, but also may aid in delivering a "neurally adjusted PEEP", and more specific breath-by-breath unloading. METHODS: Nine adult New Zealand white rabbits were ventilated during independent conditions of: resistive loading (RES(1) or RES(2)), CO2 load (CO2) and acute lung injury (ALI), either via tracheotomy (INV) or non-invasively (NIV). There were a total of six conditions, applied in a non-randomized fashion: INV-RES(1), INV-CO2, NIV-CO2, NIV-RES(2), NIV-ALI, INV-ALI. For each condition, tNAVA was applied first (3 min), followed by 3 min of cNAVA. This comparison was repeated 3 times (repeated cross-over design). The NAVA level was always the same for both modes, but was newly titrated for each condition. PEEP was manually set to zero during tNAVA. During cNAVA, the assist during expiration was proportional to the EAdi. During all runs and conditions, ventilator-delivered pressure (Pvent), esophageal pressure (Pes), and diaphragm electrical activity (EAdi) were measured continuously. The tracings were analyzed breath-by-breath to obtain peak inspiratory and mean expiratory values. RESULTS: For the same peak Pvent, the distribution of inspiratory and expiratory pressure differed between tNAVA and cNAVA. For each condition, the mean expiratory Pvent was always higher (for all conditions 4.0 +/- 1.1 vs. 1.1 +/- 0.5 cmH2O, P < 0.01) in cNAVA than in tNAVA. Relative to tNAVA, mean inspiratory EAdi was reduced on average (for all conditions) by 19 % (range 14 %-25 %), p < 0.05. Mean expiratory EAdi was also lower during cNAVA (during INV-RES(1), INV-CO2, INV-ALI, NIV-CO2 and NIV-ALI respectively, P < 0.05). The inspiratory Pes was reduced during cNAVA all 6 conditions (p < 0.05). Unlike tNAVA, during cNAVA the expiratory pressure was comparable with that predicted mathematically (mean difference of 0.2 +/- 0.8 cmH2O). CONCLUSION: Continuous NAVA was able to apply neurally adjusted PEEP, which led to a reduction in inspiratory effort compared to triggered NAVA. PMID- 26369673 TI - Making Sense of an Unknown Terrain: How Parents Understand Self-Harm in Young People. AB - Self-harm is common in young people, and can have profound effects on parents and other family members. We conducted narrative interviews with 41 parents and other family members of 38 young people, aged up to 25, who had self-harmed. Most of the participants were parents but included one sibling and one spouse. This article reports experiences of the parent participants. A cross-case thematic analysis showed that most participants were bewildered by self-harm. The disruption to their worldview brought about by self-harm prompted many to undergo a process of "sense-making"-by ruminative introspection, looking for information, and building a new way of seeing-to understand and come to terms with self-harm. Most participants appeared to have been successful in making sense of self-harm, though not without considerable effort and emotional struggle. Our findings provide grounds for a deeper socio-cultural understanding of the impact of self harm on parents. PMID- 26369675 TI - Urethral stricture secondary to self-instrumentation due to delusional parasitosis: a case report. AB - INTRODUCTION: Delusional parasitosis is a rare psychiatric disorder which often presents with dermatological problems. Delusional parasitosis, which involves urethral self-instrumentation and foreign body insertion, is exceptionally rare. This is the first case report to date that provides a detailed presentation of the urological manifestation of delusional parasitosis with complications associated with repeated self-instrumentation and foreign body insertion, resulting in stricture formation and requiring perineal urethrostomy. CASE PRESENTATION: A 45-year-old Irish man was electively admitted for perineal urethrostomy with chronic symptoms of dysuria, haematuria, urethral discharge, and intermittent urinary retention. He reported a 4-year history of intermittent pain, pin-prick biting sensations, and burrowing sensations, and held the belief that his urethra was infested with ticks. He also reported a 2-year history of daily self-instrumentation, mainly injecting an antiseptic using a syringe in an attempt to eliminate the ticks. He was found to have urethral strictures secondary to repeated self-instrumentation. A foreign body was found in his urethra and was removed via cystoscopy. On psychiatric assessment, he displayed a fixed delusion of tick infestation and threatened to surgically remove the tick himself if no intervention was performed. The surgery was postponed due his mental state and he was started on risperidone; he was later transferred to an acute in-patient psychiatric unit. Following a 3-week admission, he reported improvement in his thoughts and distress. CONCLUSIONS: Delusional parasitosis is a rare psychiatric disorder. Self-inflicted urethral foreign bodies in males are rare and have high comorbidity with psychiatric disorders; hence, these patients have a low threshold for referral for psychiatric assessment. The mainstay treatment for delusional parasitosis is second-generation antipsychotic drugs. PMID- 26369677 TI - The role of interleukin 35 in atherosclerosis. AB - Atherosclerosis has been widely recognized as a slow progressing inflammatory disease of the arterial walls involving both inflammation and autoimmune processes with a complex etiology in which the immune system plays a key role. A hallmark of atherosclerosis is that the macrophages pick up the lipids to form the foam cells which build up the plaque in the arterial wall. Consequently, the arteries become narrowed. Plaque rupture can trigger thrombosis which is superimposed on atherosclerotic lesion. The activation of macrophages and T cells plays key roles in these lesions. Cells involved in the atherosclerotic process secrete soluble factors, known as cytokines. These cytokines can be further divided into two classes namely proinflammatory and anti-inflammatory cytokines based on their roles in inflammation. Among the cytokines, interleukin (IL)-35 is the one most recently discovered that suppresses inflammatory responses of immune cells. Accumulating evidence suggests that IL-35 represents an attractive target for anti-atherosclerotic therapy based on its several atheroprotective features. In this review, we will provide a brief overview of IL-35 biology and the role of IL-35 in the development, or the progression of atherosclerosis. PMID- 26369676 TI - Recent Advances of Radionuclide-Based Molecular Imaging of Atherosclerosis. AB - Atherosclerosis is a systemic disease characterized by the development of multifocal plaque lesions within vessel walls and extending into the vascular lumen. The disease takes decades to develop symptomatic lesions, affording opportunities for accurate detection of plaque progression, analysis of risk factors responsible for clinical events, and planning personalized treatment. Of the available molecular imaging modalities, radionuclidebased imaging strategies have been favored due to their sensitivity, quantitative detection and pathways for translational research. This review summarizes recent advances of radiolabeled small molecules, peptides, antibodies and nanoparticles for atherosclerotic plaque imaging during disease progression. PMID- 26369674 TI - Human skeletal muscle fibre contractile properties and proteomic profile: adaptations to 3 weeks of unilateral lower limb suspension and active recovery. AB - KEY POINTS: It is generally assumed that muscle fibres go through atrophy following disuse with a loss of specific force and an increase in unloaded shortening velocity. However, the underlying mechanisms remain to be clarified. Most studies have focused on events taking place during the development of disuse, whereas the subsequent recovery phase, which is equally important, has received little attention. Our findings support the hypotheses that the specific force of muscle fibres decreased following unilateral lower limb suspension (ULLS) and returned to normal after 3 weeks of active recovery as a result of a loss and recovery of myosin and actin content. Furthermore, muscle fibres went through extensive qualitative changes in muscle protein pattern following ULLS, and these were reversed by active recovery. Resistance training was very effective in restoring both muscle mass and qualitative muscle changes, indicating that long-term ULLS did not prevent the positive effect of exercise on human muscle. ABSTRACT: Following disuse, muscle fibre function goes through adaptations such as a loss of specific force (PO /CSA) and an increase in unloaded shortening velocity, which could be a result of both quantitative changes (i.e. atrophy) and qualitative changes in protein pattern. The underlying mechanisms remain to be clarified. In addition, little is known about the recovery of muscle mass and strength following disuse. In the present study, we report an extensive dataset describing, in detail,the functional and protein content adaptations of skeletal muscle in response to both disuse and re training. Eight young healthy subjects were subjected to 3 weeks of unilateral lower limb suspension (ULLS), a widely used human model of disuse skeletal muscle atrophy. Needle biopsies samples were taken from the vastus lateralis muscle Pre ULLS, Post-ULLS and after 3 weeks of recovery during which heavy resistance training was performed. After disuse, cross-sectional area (CSA), PO /CSA and myosin concentration (MC) decreased in both type 1 and 2A skinned muscle fibres. After recovery, CSA and MC returned to levels comparable to those observed before disuse, whereas Po/CSA and unloaded shortening velocity reached a higher level. Myosin heavy chain isoform composition of muscle samples did not differ among the experimental groups. To study the mechanisms underlying such adaptations, a two dimensional proteomic analysis was performed. ULLS induced a reduction of myofibrillar, metabolic (glycolytic and oxidative) and anti-oxidant defence system protein content. Resistance training was very effective in counteracting ULLS-induced alterations, indicating that long-term ULLS did not prevent the positive effect of exercise on human muscle. PMID- 26369678 TI - Can We Select Patients for Colorectal Cancer Prevention with Aspirin? AB - Aspirin has been extensively investigated in the context of the prevention of cardiovascular disease. It has one of the strongest cumulative evidence supporting its use in colorectal cancer (CRC) chemoprevention. Epidemiological, clinical, and observational studies have demonstrated that aspirin and non steroidal antiinflammatory drugs (NSAIDs), including COX-2 inhibitors, can protect against CRC and significantly reduce its incidence. Moreover, prospective randomized controlled trials of colorectal polyp recurrence and in patients with hereditary CRC syndromes have shown that aspirin can produce regression of existing colorectal adenomas and prevent the formation of new polyps. However, the lowest effective doses, treatment duration, target populations, and the effects on survival are not entirely clear. Although not common serious side effects and in particular gastrointestinal and intracerebral hemorrhage do occur, better selection of individuals who might benefit the most from aspirin use must be carefully performed in order to maximize their risk/benefit ratio. In the era of precision medicine, genetic information, blood and/or urinary biomarkers, could potentially help in tailoring chemopreventive therapeutic strategies, based on aspirin use, while limiting adverse toxic effects. The current review will cover the use of aspirin for the prevention of colorectal adenomas and CRC, potential markers for chemoprevention, and patient stratification. PMID- 26369679 TI - New Insights into the Mechanism of Action of Aspirin in the Prevention of Colorectal Neoplasia. AB - The results of clinical studies have shown that the chronic administration of aspirin, even at the lowdoses (75-100 mg daily) recommended for the prevention of cardiovascular disease, is associated with a reduction of cancer incidence and mortality, in particular colorectal cancer (CRC). The mechanism of action of aspirin as an antineoplastic agent remains controversial. However, data of clinical pharmacology and several features of the chemopreventive effect of aspirin, emerged from clinical trials, suggest that the antiplatelet effect of aspirin plays a central role in its anticancer effects. In addition to their contribution to tumor metastasis, platelets may play a role in the early phases of tumorigenesis. In response to lifestyle and environment factors, intestinal epithelial damage/ dysfunction may be associated with platelet activation, initially as a mechanism to repair the damage. However, if the platelet response is unconstrained, it may contribute to the development of chronic inflammation. Altogether these events lead to alter the normal functions of intestinal epithelial cells and may translate into cellular transformation through several mechanisms, including the overexpression of cyclooxygenase(COX)-2 and epidermal growth factor receptor (EGFR), which are considered early events in colorectal tumorigenesis. Thus, antiplatelet agents may play a role in the prevention of CRC by modifying epigenetic events involved in early phases of colorectal tumorigenesis. Finally, we carried out a critical review of the literature on off target mechanisms of aspirin action as anticancer drug. PMID- 26369680 TI - Aspirin Use on Incidence and Mortality of Gastrointestinal Cancers: Current State of Epidemiological Evidence. AB - Aspirin has been one of the most widely used medications since its first synthesis more than 100 years ago. In addition to short-term use for pain and fever relief, regular use of aspirin has been shown to reduce the risk of cardiovascular diseases and strokes. The issue of regular aspirin use in cancer prevention is definitely promising, which has been supported by growing evidence from a number of observational studies and post-trial follow-up data. Among all cancers, aspirin is showing to be the most effective in reducing the risk of colorectal cancer, and even at lower doses demonstrates a 30-40% effectiveness in preventing colorectal cancer. Esophagus and stomach cancers are two cancers getting increased attention from emerging evidence of meta-analyses. Given the common side effects of aspirin, such as gastrointestinal complications, whether it is ready to take aspirin regularly for general population remains controversial since more studies are needed to clarify the net balance between harm and benefit. The decision might become more complicated since recently one molecular epidemiology study showed that different genetic traits may impact the effect of aspirin on colorectal cancer. Here we summarize recent evidence from meta-analyses related to gastrointestinal cancers. We reviewed updated observational studies and post-trial follow up data from randomized controlled trials focusing on the role of aspirin in the incidence and mortality of gastrointestinal cancers. PMID- 26369681 TI - A Balanced View of Efficacy and Safety of Aspirin in Cardiovascular Diseases. AB - This review highlights practical aspects related to aspirin therapy in cardiovascular diseases, specifically, the benefits and hazards in different clinical settings. Aspirin reduces one fourth of all major cardiovascular events but also increases major gastrointestinal bleeds by about half. As with other cardiovascular prevention strategies, the absolute benefit of aspirin is linearly related to the cardiovascular risk of the patient. The risk-benefit of aspirin can vary substantially in different settings: in secondary prevention, the benefits usually outweigh the excess of major bleeding complications. In primary prevention, it is not unusual that the number of vascular events avoided equals the number of major bleeds induced by aspirin. Finally, there is a growing body of evidence suggesting that aspirin may interfere with the early stages of cancer, metastasis and mortality. For all these reasons, in this article new developments in the field directed towards individualized risk assessment strategies are also discussed. PMID- 26369682 TI - Epidemiology of Low Dose Aspirin Damage in the Lower Gastrointestinal Tract. AB - Low dose aspirin (ASA), commonly defined as the cardiovascular (CV) dose of 75 to 325 mg daily, is one of the most widely prescribed drugs in the world and the cornerstone of therapy and prophylaxis for CV disease. However, the use of low dose ASA is well known to be associated with an increased risk of different upper and lower gastrointestinal (GI) complications, such as peptic ulceration and bleeding. In the recent past, clinical research was mainly focused on ASA-related injury of the upper GI tract. However, the introduction of new endoscopic techniques, such as capsule endoscopy and balloon-assisted endoscopy for the evaluation of small bowel lesions have resulted in an increasing interest among gastroenterologists about the side effects of ASA on the large and small bowel. Furthermore, it has been demonstrated that chronic use of low dose ASA results in a variety of lesions in the lower GI tract, including multiple petechiae, erosions, ulcers, diverticular bleeding and even circumferential ulcers with stricture. The ideal treatment for small bowel injury in low dose ASA users would be withdrawal of ASA, however, this withdrawal could increase the risk of CV/cerebrovascular morbidity and mortality in high percentage of patients. Therefore, several drugs have been evaluated to identify the best choice to prevent or treat ASA-induced small bowel injury with different results. Nevertheless, further specifically designed studies with more sample size are needed to determine the best treatment for low dose ASA related GI injury. PMID- 26369683 TI - Aspirin Induced Adverse Effects on the Small and Large Intestine. AB - Aspirin is in many ways a non- steroidal anti-inflammatory drug (NSAID) prototype. Similar to conventional NSAIDs the gastric side effects of aspirin are well studied. However its potential adverse effects on the small and large intestine are less well known and under- researched. Experimental studies support a pathogenic pathway leading to NSAID enteropathy involving the topical effects on the intestinal barrier (mucous layer, enterocytes) that lead to dysfunction and increased intestinal permeability followed by increased exposure to luminal triggers and acute inflammation. Although aspirin has a toxic effect in vitro, enteral or parenteral administration in vivo, in animal models, did not result to intestinal injury. In man, experimental studies have revealed changes in intestinal permeability similar to conventional NSAIDs but of lesser magnitude. The clinical implication of these changes though is not known. Population studies have associated aspirin use with occult gastrointestinal bleeding from the small or large bowel although the magnitude of this risk is difficult to estimate but certainly small. Associations to colitis flare-ups have been made in case reports and retrospective cohort studies but low dose aspirin appears safe. Complications of diverticular disease may also be more frequent with aspirin use. PMID- 26369684 TI - Prevention of Upper Gastrointestinal Ulcer and Complications in Low-Dose Aspirin Users. AB - Low-dose aspirin (LDA) has been increasingly used worldwide to prevent atherothrombotic events. At the same time, the adverse events, most frequent of which are gastrointestinal (GI) ulcers and complications have been raising a big concern with its wider use. These adverse events including reflux and dyspeptic symptoms not only jeopardize adherence of LDA, but my cause more serious outcomes. To reduce GI events by informing best evidence for physicians prescribing LDA, guidelines were published some years ago. Since then, more clinical evidence concerning preventive strategies for upper GI events has been accumulated. Notable differences between East and West are also recognized in terms of primary prevention strategy. Among several options to provide cardiovascular protection with LDA while reducing GI risk, PPI co-therapy is considered to be preferred approach for wider populations according to recent cost-effectiveness analyses based on increasing awareness of importance on adherence of LDA together with declining cost of PPI. This review will focus on these new developments on the prevention of upper gastrointestinal ulcer and complications in LDA users. PMID- 26369685 TI - Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Induced Dyspepsia. AB - Non-steroidal anti-inflammatory drugs (NSAIDs) are the most prescribed group of drugs in the world. They are used primarily for pain relief in chronic inflammatory joint disease and act by inhibiting enzymes COX1 and COX2 and ultimately preventing the production of active prostanoids which are required for the innate inflammatory pathway. The use of NSAIDs have been associated with the development of gastrointestinal (GI) symptoms ranging from simple dyspepsia to life threatening GI bleeds and perforations. The definition of dyspepsia has evolved over the years and this has hampered accurate studies on the prevalence of dyspepsia as different studies used varying criteria to define dyspepsia. It is now known that NSAIDs significantly increase the risk of dyspepsia.The risk of developing peptic ulcer disease vary with specific NSAIDs and dosages but there is no correlation between the symptoms of dyspepsia and underlying peptic ulcers. The pathogenesis of dyspepsia with NSAIDs is not completely understood. Peptic ulceration alone is not able to account for the majority of dyspepsia symptoms encountered by NSAIDs users. Erosive oesophagitis secondary to NSAIDs may be contributing factor to the prevalence of dyspepsia in NSAIDs users. Altered gut permeability and changes in gastric mechanosensory function due to NSAIDs may also be a contributory factor. Management of NSAID induced dyspepsia is involves a multipronged approach. Drug avoidance if possible would be ideal. Other options include using the lowest effective dose, changing to an NSAIDs with a safer GI risk profile, avoiding concurrent use with other NSAIDs or if the patient has a previous history of peptic ulcer disease, and co-prescribing with anti-secretory medications such as proton pump inhibitors. Eradication of Helicobacter pylori has a protective role against developing peptic ulcers and may also improve symptoms of NSAIDs induced dyspepsia. PMID- 26369686 TI - Low-Dose Aspirin-Associated Upper and Mid Gastrointestinal Tract Damage and Gene Polymorphism. AB - The risk of gastrointestinal (GI) bleeding is increased in association with the use of low-dose aspirin (LDA). There are few studies of the association between genetic polymorphisms and the risks of aspirin-induced ulcer or its complications. Individuals with two single nucleotide polymorphisms (SNPs) of cyclooxygenase-1 (COX-1), A-842G and C50T, exhibit increased sensitivity to aspirin and lower prostaglandin synthesis capacity but the polymorphism lacked statistical significance in relation to an association with bleeding peptic ulcer. In our previous Japanese study, SLCO1B1 521TT genotype and the SLCO1B1 *1b haplotype were significantly associated with the risk of peptic ulcer and ulcer bleeding in patients taking LDA, especially in the patients with angiotensin converting enzyme inhibitor (ACEI), angiotensin type 1 receptor blocker (ARB), or statin co-treatment. Protonpump inhibitors (PPIs) are recommended for patients who require antiplatelet therapy and have a history of upper GI bleeding. The interaction between PPIs and consequent impaired effectiveness of clopidogrel has caused concern regarding the effect of genetic polymorphisms of the CYP2C19 which mediates conversion of clopidogrel to its active metabolite. The later recent genome-wide analysis of SNPs indicated the association of several SNPs with small bowel bleeding in Japanese patients taking LDA. The data are still lacking and further prospective studies are needed to identify the specific gene polymorphisms as risk or protective factors for GI bleeding associated with LDA. PMID- 26369687 TI - Risk Factors for Upper GI Damage in Low-Dose Aspirin Users and the Interaction Between H. pylori Infection and Low-Dose Aspirin Use. AB - Nowadays, low-dose aspirin is widely administered at low dose as an antithrombotic drug for the prevention of cerebrovascular and cardiovascular diseases. However, aspirin, even at a low dose, can induce varying degrees of gastroduodenal mucosal injury (erosion, ulcer, ulcer bleeding). Hence, co prescription of proton pump inhibitors with low-dose aspirin is recommended for those at high risk for adverse gastroduodenal events. At present, a history of peptic ulcer, especially that of complicated ulcer, is the most important risk factor for low-dose aspirin-associated gastroduodenal adverse events. Additionally, concomitant use of non-steroidal anti-inflammatory drugs including COX-2 selective inhibitors, anti-platelet agents, anti-coagulants, and oral corticosteroid is recognized to increase the risk for adverse gastroduodenal events in low-dose aspirin users. H. pylori infection could also be associated with the increased risk for adverse gastroduodenal events in low-dose aspirin users, especially in patients with histories of peptic ulcers. Therefore, eradication therapy for such patients can prevent ulcer recurrence. However, the efficacy of eradication therapy on low-dose aspirin-related gastroduodenal lesions in unselected H. pylori-positive lowdose aspirin users without histories of peptic ulcers remains to be clarified. PMID- 26369688 TI - Epidemiology of Upper Gastrointestinal Damage Associated with Low-Dose Aspirin. AB - Low-dose aspirin, commonly defined as 75-325 mg daily, is widely used for cardiovascular (CV) protection. It reduced the risk of CV events and death in patients with coronary and cerebrovascular diseases and has the advantages of both low cost and long duration of antiplatelet action. However, low-dose aspirin therapy is associated with upper gastrointestinal (GI) side effects, which range from dyspepsia (point prevalence: 31%), gastroduodenal erosions (point prevalence: 60%), endoscopic peptic ulcer (3-month incidence: 7%) to symptomatic or complicated ulcers (annual incidence of upper GI bleeding: 0.6%; relative risk of upper GI bleeding: 2.6). The important factors that increase the risk of low dose aspirin-related ulcer complications include a history of bleeding peptic ulcer, prior peptic ulcer, age > 70 years, H pylori infection, and concomitant drug therapy with non-steroidal anti-inflammatory drugs, other antiplatelet agents (e.g., clopidogrel) or anticoagulants. The use of enteric-coated or buffered preparations do not reduce the risk of upper GI complications. Assessment of GI risk for patients is a crucial step in preventing complications of antiplatelet agents. Patients with a high GI risk should prevent peptic ulcer or ulcer complications by co-therapy with an antisecretory agent, especially proton pump inhibitors. H pylori eradication is recommended for patients requiring long-term low-dose aspirin therapy who have a prior history of peptic ulcer or GI bleeding. PMID- 26369689 TI - An age-period-cohort analysis of female breast cancer mortality from 1990-2009 in China. AB - BACKGROUND: Breast cancer is the most common cause of cancer-related death among women. In this paper, we studied the variations in the trends of Chinese female breast cancer mortality by age, period and cohort from 1990 to 2009. METHODS: The mortality data were collected from the Institute for Health Metrics and Evaluation. An age-period-cohort model and Intrinsic Estimator were used to estimate the age effect, period effect and cohort effect on the Chinese adult female breast cancer mortality risk. RESULTS: The age effect on Chinese female breast cancer mortality initially increased, but then declined, and showed a reversed "J" shape with age. The period effect of breast cancer mortality continued to rise with the time period and increased by 59% from 1990-1994 to 2005-2009. The cohort effect showed that the mortality risk of Chinese females born after 1911 was on the decline and decreased by 2.2336 from 1911 to 1989. The change rate of the cohort effect on breast cancer mortality fluctuated regularly. Three accelerating decreases and three decelerating decreases were noted in the variation law of the change rate. CONCLUSION: The results of study show the increasing mortality trend of breast cancer in Chinese female from 1990 to 2009, and the breast cancer mortality risk decreased with birth cohort. PMID- 26369690 TI - Impaired fasting glucose and left ventricular diastolic dysfunction in middle-age adults: a retrospective cross-sectional analysis of 2971 subjects. AB - BACKGROUND: Left ventricular (LV) diastolic dysfunction (LVDD) is a well established and early echocardiographic characteristic of diabetic cardiomyopathy. However, there are limited data on the association between impaired fasting glucose (IFG) and LVDD. OBJECTIVE: To determine whether IFG is associated with LVDD among middle age adults. METHODS: Amongst 3781 subjects screened in an annual health survey program and referred for an echocardiogram, 2971 individuals without LV systolic dysfunction or valvular heart disease were selected. Mean age of study population was 59 +/- 12 years and 75% were men. The subjects were categorized into three groups: euglycemia (N = 2025), IFG (N = 534) and diabetes mellitus (DM; N = 412). Doppler echocardiography readers were blinded to glycemic state. Subjects with impaired LV relaxation, pseudo-normal or restrictive filling patterns were defined as having LVDD. RESULTS: LVDD was diagnosed in 574 (19 %) of subjects and it was more prevalent among patients with IFG and DM than in euglycemic individuals (27, 30 and 15%, respectively; p < 0.001). Patients with IFG and DM had lower ratios of early (E) to late (A) trans mitral flow (0.9 +/- 0.3 and 0.9 +/- 0.3 vs. 1.1 +/- 0.4, respectively, p < 0.001). LV hypertrophy (LVH) was also more prevalent among patients with IFG and DM (11 and 18%, respectively, vs. 9%; p < 0.001). Multivariate binary logistic regression model adjusted to age, gender, obesity, LVH, renal function, total, high and low density lipoprotein cholesterol, triglycerides, ischemic heart disease, hypertension and LV ejection fraction showed that patients with IFG were 43% more likely to have LVDD compared with euglycemic subjects (95% confidence interval 1.12-1.83, p = 0.004). CONCLUSIONS: IFG is independently associated with a significant increase in the likelihood for the presence of LVDD in middle aged adults. PMID- 26369691 TI - Wnt3a: functions and implications in cancer. AB - Wnt3a, one of Wnt family members, plays key roles in regulating pleiotropic cellular functions, including self-renewal, proliferation, differentiation, and motility. Accumulating evidence has suggested that Wnt3a promotes or suppresses tumor progression via the canonical Wnt signaling pathway depending on cancer type. In addition, the roles of Wnt3a signaling can be inhibited by multiple proteins or chemicals. Herein, we summarize the latest findings on Wnt3a as an important therapeutic target in cancer. PMID- 26369693 TI - PLA2R and membranous nephropathy: A 3 year prospective Australian study. AB - AIM: The phospholipase A2 receptor (PLA2R) is the major target antigen in idiopathic membranous nephropathy (iMN). The aim of this prospective study was to determine the prevalence of anti-PLA2R in iMN in an Australian cohort. METHODS: Serum anti-PLA2R was measured using two techniques, an enzyme-linked immunosorbent assay (ELISA) and a cell-based indirect immunofluorescence test. Kidney biopsies were also examined for the presence of PLA2R using a polyclonal antibody. A group of 21 patients with iMN were compared with a group of 19 patients with secondary MN and other glomerular diseases. RESULTS: Seventeen of 21 patients with iMN were positive for anti-PLA2R on both ELISA and indirect immunofluorescence test, and 14 of these patients also had positive staining for PLA2R in the biopsy (tissue was unavailable in two patients). Three patients with iMN had positive staining in the biopsy only, and one patient was negative in both the serum and the biopsy. None of the patients with secondary MN or other glomerular diseases had anti-PLA2R antibodies or PLA2R in the biopsy. There was wide inter-individual variation in titre on ELISA, but serial levels within an individual patient enabled monitoring of disease, and a fall in titre correlated with clinical remission. CONCLUSIONS: This is the first Australian series to examine the incidence of anti-PLA2R in iMN. It is also unique in examining sera by two separate techniques in conjunction with tissue localization of PLA2R. We have shown 100% specificity of both serum anti-PLA2R and glomerular PLA2R in iMN, with a sensitivity of 81.0%. When serum testing is combined with tissue localization of PLA2R, the sensitivity increases to 95.2%. PMID- 26369692 TI - Bioaccumulation and biological effects of cigarette litter in marine worms. AB - Marine debris is a global environmental issue. Smoked cigarette filters are the predominant coastal litter item; 4.5 trillion are littered annually, presenting a source of bioplastic microfibres (cellulose acetate) and harmful toxicants to marine environments. Despite the human health risks associated with smoking, little is known of the hazards cigarette filters present to marine life. Here we studied the impacts of smoked cigarette filter toxicants and microfibres on the polychaete worm Hediste diversicolor (ragworm), a widespread inhabitant of coastal sediments. Ragworms exposed to smoked cigarette filter toxicants in seawater at concentrations 60 fold lower than those reported for urban run-off exhibited significantly longer burrowing times, >30% weight loss, and >2-fold increase in DNA damage compared to ragworms maintained in control conditions. In contrast, ragworms exposed to smoked cigarette filter microfibres in marine sediment showed no significant effects. Bioconcentration factors for nicotine were 500 fold higher from seawater than from sediment. Our results illustrate the vulnerability of organisms in the water column to smoking debris and associated toxicants, and highlight the risks posed by smoked cigarette filter debris to aquatic life. PMID- 26369694 TI - Shear-Dependent Interactions of von Willebrand Factor with Factor VIII and Protease ADAMTS 13 Demonstrated at a Single Molecule Level by Atomic Force Microscopy. AB - Vital functions of mammals are only possible due to the behavior of blood to coagulate most efficiently in vessels with particularly high wall shear rates. This is caused by the functional changes of the von Willebrand Factor (VWF), which mediates coagulation of blood platelets (primary hemostasis) especially when it is stretched under shear stress. Our data show that shear stretching also affects other functions of VWF: Using a customized device to simulate shear conditions and to conserve the VWF molecules in their unstable, elongated conformation, we visualize at single molecule level by AFM that VWF is preferentially cleaved by the protease ADAMTS13 at higher shear rates. In contrast to this high shear-rate-selective behavior, VWF binds FVIII more effectively only below a critical shear rate of ~30.000 s(-1), indicating that under harsh shear conditions FVIII is released from its carrier protein. This may be required to facilitate delivery of FVIII locally to promote secondary hemostasis. PMID- 26369696 TI - Celebrating Soft Matter's 10th Anniversary: Influencing the charge of poly(methyl methacrylate) latexes in nonpolar solvents. AB - Sterically-stabilized poly(methyl methacrylate) (PMMA) latexes dispersed in nonpolar solvents are a classic, well-studied system in colloid science. This is because they can easily be synthesized with a narrow size distribution and because they interact essentially as hard spheres. These PMMA latexes can be charged using several methods (by adding surfactants, incorporating ionizable groups, or dispersing in autoionizable solvents), and due to the low relative permittivity of the solvents (epsilonr ~ 2 for alkanes to epsilonr ~ 8 for halogenated solvents), the charges have long-range interactions. The number of studies of these PMMA particles as charged species has increased over the past ten years, after few studies immediately following their discovery. A large number of variations in both the physical and chemical properties of the system (size, concentration, surfactant type, or solvent, as a few examples) have been studied by many groups. By considering the literature on these particles as a whole, it is possible to determine the variables that have an effect on the charge of particles. An understanding of the process of charge formation will add to understanding how to control charge in nonaqueous solvents as well as make it possible to develop improved technologically relevant applications for charged polymer nanoparticles. PMID- 26369695 TI - Studying the consumption and health outcomes of fiscal interventions (taxes and subsidies) on food and beverages in countries of different income classifications; a systematic review. AB - BACKGROUND: Governments use fiscal interventions (FIs) on food and beverages to encourage healthy food behaviour and positive health outcomes. The objective of this review was to study the behavioural and health outcomes of implemented food and beverage FIs in the form of taxes and subsidies in countries of different income classifications. METHODS: The present systematic review was conducted in accordance with Cochrane protocols. The search was carried out on academic and grey literature in English, for studies conducted in different countries on implemented FIs on food and non-alcoholic beverages and health outcomes, with a special focus on the income of those countries. RESULTS: Eighteen studies met the inclusion criteria and 14 were from peer- reviewed journals. Thirteen studies came from high-income (HI) countries, four from upper middle-income (UMI) countries and only one came from a lower middle-income (LMI) country. There were no studies from lower-income (LI) countries. Of these 18 studies; nine focused on taxes, all of which were from HI countries. Evidence suggests that FIs on foods can influence consumption of taxed and subsidized foods and consequently have the potential to improve health. CONCLUSION: Although this review supports previous findings that FIs can have an impact on healthy food consumption, it also highlights the lack of evidence available from UMI, LMI and LI countries on such interventions. Therefore, evidence from HI countries may not be directly applicable to middle-income and LI countries. Similar research conducted in middle and low income countries will be beneficial in advocating policy makers on the effectiveness of FIs in countering the growing issues of non-communicable diseases in these countries. PMID- 26369697 TI - Small Intestinal Submucosa Implantation for the Possible Treatment of Vocal Fold Scar, Sulcus, and Superficial Lamina Propria Atrophy. AB - OBJECTIVES: Evaluate the histologic effects of grafting porcine-derived small intestinal submucosa (SIS) into the vocal fold superficial lamina propria (SLP) layer for the potential treatment of vocal fold scar, sulcus and superficial lamina propria atrophy. METHODS: Small intestinal submucosa was implanted into the right vocal fold SLP of 6 mongrel dogs. The left vocal fold served as a sham surgical control. At 2, 4, and 6 weeks postoperative, bilateral vocal fold specimens were evaluated histologically. RESULTS: At 2 and 4 weeks, respectively, SIS-implanted vocal folds demonstrated moderate and mild inflammation and acute and chronic inflammation. At 6 weeks, inflammation was minimal and chronic. The 6 week specimens showed copious amounts of newly generated hyaluronic acid (HA) within the graft. There was no reactive fibrosis at 6 weeks. CONCLUSIONS: In the canine model, SIS appears safe for SLP grafting. Inflammation is similar to that of sham surgery. Small intestinal submucosa results in newly generated HA without concomitant fibrosis. Small intestinal submucosa has potential to be used in treatment of disorders with SLP, including vocal fold scar, sulcus, and atrophy. Studies evaluating the effect of SIS implantation on vocal fold function, as well as the ultimate fate of the graft, are required. PMID- 26369698 TI - Monolithic III-V on Silicon Plasmonic Nanolaser Structure for Optical Interconnects. AB - Monolithic integration of III-V semiconductor lasers with Si circuits can reduce cost and enhance performance for optical interconnects dramatically. We propose and investigate plasmonic III-V nanolasers as monolithically integrated light source on Si chips due to many advantages. First, these III-V plasmonic light sources can be directly grown on Si substrates free of crystallographic defects due to the submicron cavity footprint (250 nm * 250 nm) being smaller than the average defect free region size of the heteroepitaxial III-V material on Si. Secondly, the small lateral and vertical dimensions facilitate process co integration with Si complementary metal-oxide-semiconductor (CMOS) in the front end of the line. Thirdly, combining with monolithically integrated CMOS circuits with low device capacitance and parasitic capacitance, the nano-cavity optoelectronic devices consume orders of magnitude less power than the conventional lasers and reduce the energy consumption. Fourthly, the modulation bandwidth of the plasmonic light-sources is enhanced to significantly higher than conventional lasers due to enhanced photon state density and transition rate. In addition, we show that these device performance are very robust after taking into account the surface recombination and variations in device fabrication processes. PMID- 26369700 TI - Mitochondrial transport of protoporphyrinogen IX in erythroid cells. AB - Comment on: Yien Y, et al. TMEM14C is required for erythroid mitochondrial heme metabolism. J. Clin. Invest. 2014; 124:4294-4304. PMID- 26369699 TI - BMI Affects the Relationship between Long Chain N-3 Polyunsaturated Fatty Acid Intake and Stroke Risk: a Meta-Analysis. AB - We performed a meta-analysis to clarify the relationship between long chain n-3 polyunsaturated fatty acid (PUFA) intake and stroke risk. Relevant studies were identified by searching online databases through May 2015. Log relative risks (RRs) of the highest versus the lowest for cohort studies were weighed by the inverse variance method to obtain pooled RRs. Fourteen prospective cohort studies including 514,483 individuals and 9,065 strokes were included. The pooled RR of overall stroke risk for long chain n-3 PUFA intake was 0.87 [95% confidence interval (CI), 0.79-0.95]. Stratification analysis showed that higher long chain n-3 PUFAs intake was associated with reduced fatal stroke risk (RR = 0.84; 95% CI, 0.73-0.97), reduced stroke risk for BMI < 24 (RR = 0.86; 95% CI, 0.75-0.98) and reduced stroke risk for females (RR = 0.81; 95% CI, 0.71-0.92), but was not associated with stroke risk for either BMI >= 24 or men. This meta-analysis reveals that higher long chain n-3 PUFA intake is inversely associated with risk of stroke morbidity and mortality with BMI and sex as key factors influencing this risk. Individuals should be encouraged to manage their body weight while increasing their intake of long chain n-3 PUFAs. PMID- 26369703 TI - PyPDB: a Python API for the Protein Data Bank. AB - SUMMARY: We have created a Python programming interface for the RCSB Protein Data Bank (PDB) that allows search and data retrieval for a wide range of result types, including BLAST and sequence motif queries. The API relies on the existing XML-based API and operates by creating custom XML requests from native Python types, allowing extensibility and straightforward modification. The package has the ability to perform many types of advanced search of the PDB that are otherwise only available through the PDB website. AVAILABILITY AND IMPLEMENTATION: PyPDB is implemented exclusively in Python 3 using standard libraries for maximal compatibility. The most up-to-date version, including iPython notebooks containing usage tutorials, is available free-of-charge under an open-source MIT license via GitHub at https://github.com/williamgilpin/pypdb, and the full API reference is at http://williamgilpin.github.io/pypdb_docs/html/. The latest stable release is also available on PyPI. CONTACT: wgilpin@stanford.edu. PMID- 26369701 TI - Negative prognostic impact of regulatory T cell infiltration in surgically resected esophageal cancer post-radiochemotherapy. AB - Ever accumulating evidence indicates that the long-term effects of radiotherapy and chemotherapy largely depend on the induction (or restoration) of an anticancer immune response. Here, we investigated this paradigm in the context of esophageal carcinomas treated by neo-adjuvant radiochemotherapy, in a cohort encompassing 196 patients. We found that the density of the FOXP3+ regulatory T cell (Treg) infiltrate present in the residual tumor (or its scar) correlated with the pathological response (the less Tregs the more pronounced was the histological response) and predicted cancer-specific survival. In contrast, there was no significant clinical impact of the frequency of CD8+ cytotoxic T cells. At difference with breast or colorectal cancer, a loss-of-function allele of toll like receptor 4 (TLR4) improved cancer-specific survival of patients with esophageal cancer. While a loss-of-function allele of purinergic receptor P2X, ligand-gated ion channel, 7 (P2RX7) failed to affect cancer-specific survival, its presence did correlate with an increase in Treg infiltration. Altogether, these results corroborate the notion that the immunosurveillance seals the fate of patients with esophageal carcinomas treated with conventional radiochemotherapy. PMID- 26369702 TI - Combination genetic signature stratifies lower-grade gliomas better than histological grade. AB - We studied if combination genetic signature potentially stratifies lower-grade gliomas better than histology by investigating 214 lower-grade gliomas for IDH1/2 and TERTp mutations, 1p/19q codeletion and EGFR amplification as to their impact on prognostication. Prognostic association of grading was independent of other prognostic variables including age, histological type, IDH1/2, 1p/19q and TERTp status. No single marker, including IDH1/2, superseded grading in prognostication, indicating grading was still a very important tool. Prognosis was most favorable in 31.7% of patients with IDH1/2 mutation and either 1p/19q codeletion or TERTp mutation (IDHmut-OT), intermediate in 45.8% of patients with IDH1/2 mutation only (IDHmut) and 16.9% of patients without any of the alterations (IDHwt), and poorest in 5.6% of patients with wild-type IDH1/2 and either TERTp mutation or EGFR amplification (IDHwt-ET). Our results suggested not all IDH1/2 wild-type lower-grade gliomas are aggressive and additional biomarkers are required to identify glioblastoma-equivalent tumors. Multivariate analysis revealed independent prognostic values of grading and genetic signature. Grade II IDHwt-ET gliomas exhibited shorter survival than IDH1/2 mutated grade III gliomas, suggesting combination genetic signature potentially superseded grading in prognostication. In summary, biomarker-based stratification is useful in the diagnosis and prognostication of lower-grade gliomas, and should be used together with grading. PMID- 26369706 TI - Does epigenetic dysregulation of pancreatic islets contribute to impaired insulin secretion and type 2 diabetes? AB - beta cell dysfunction is central to the development and progression of type 2 diabetes (T2D). T2D develops when beta cells are not able to compensate for the increasing demand for insulin caused by insulin resistance. Epigenetic modifications play an important role in establishing and maintaining beta cell identity and function in physiological conditions. On the other hand, epigenetic dysregulation can cause a loss of beta cell identity, which is characterized by reduced expression of genes that are important for beta cell function, ectopic expression of genes that are not supposed to be expressed in beta cells, and loss of genetic imprinting. Consequently, this may lead to beta cell dysfunction and impaired insulin secretion. Risk factors that can cause epigenetic dysregulation include parental obesity, an adverse intrauterine environment, hyperglycemia, lipotoxicity, aging, physical inactivity, and mitochondrial dysfunction. These risk factors can affect the epigenome at different time points throughout the lifetime of an individual and even before an individual is conceived. The plasticity of the epigenome enables it to change in response to environmental factors such as diet and exercise, and also makes the epigenome a good target for epigenetic drugs that may be used to enhance insulin secretion and potentially treat diabetes. PMID- 26369707 TI - Prevention of ovarian hyperstimulation syndrome in a rat model: comparison of the efficacy of tocilizumab with that of ranibizumab, cabergoline, and a gonadotropin releasing hormone antagonist. AB - The aim of the study is to investigate the effects of the interleukin-6 (IL-6) blocker tocilizumab in a hyperstimulated rat model and compare it with ranibizumab, a gonadotropin-releasing hormone antagonist (GnRHA), and cabergoline. Forty-seven rats were randomly divided into the following seven groups: Group 1: OHS; Group 2: OHS+ GnRHA; Group 3: OHS + ranibizumab; Group 4: OHS + cabergoline; Group 5: OHS + low-dose tocilizumab (TL); Group 6: OHS + high dose tocilizumab (TH); Group 7: sham. Ovarian weight was significantly lower only in the ranibizumab group than in the OHS group. Estrogen levels were significantly lower in the GnRHA group than in the OHS and the treatment groups. Progesterone levels were significantly lower in the ranibizumab, cabergoline, and TL groups than in the OHS group. Among the treatment groups, corpus luteum counts were lower than in the OHS group. Corpus luteum counts were lowest in the tocilizumab groups. IL-6 intensity was lower in all treatment groups than in the OHS group. In the ranibizumab group IL-6 intensity was the lowest. The TL group did not significantly differ from the GnRHA and cabergoline groups regarding IL-6 expression. Ovarian VEGF expression was significantly lower in all treatment groups. For the TL, ranibizumab, and cabergoline groups VEGF intensity was similar. Tocilizumab may be a new strategy for preventing ovarian hyperstimulation syndrome by inhibition of IL-6. PMID- 26369708 TI - Caspofungin: Pharmacodynamics, pharmacokinetics, clinical uses and treatment outcomes. AB - Over the past decade, echinocandins have emerged as first-line antifungal agents for many Candida infections. The echinocandins have a unique mechanism of action, inhibiting the synthesis of beta-1,3-d-glucan polymers, key components of the cell wall in pathogenic fungi. Caspofungin was the first echinocandin antifungal agent to become licensed for use. The objectives of this review are to summarize the existing published data on caspofungin, under the subject headings of chemistry and mechanism of action, spectrum of activity, pharmacodynamics, pharmacokinetics, clinical studies, safety, drug interactions, dosing, and an overview of the drug's current place in therapy. PMID- 26369709 TI - Synthesis and Anti-cancer Activity of Novel Thiazolidinone Analogs of 6 Aminoflavone. AB - Novel heterocyclic analogs were synthesized by combining a flavone nucleus and thiazolidinone ring in an effort to potentiate the existing anti-cancer activity of flavone. The syntheses of 6-aminoflavone, 6-amino-3-methoxyflavone, 6-amino-3 methoxy-3',4'-dimethxyflavone and their corresponding thiazolidinone analogs were performed. Fifteen novel analogs were synthesized and evaluated for their anti cancer activity using cell-based assay techniques and in vivo testing. As expected, the analogs improved cytotoxicity and were shown to increase the life span of cancer-bearing mice. Cytotoxicity was evaluated using 3-(4,5 dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assays in HeLa, MDA MB-435, and Vero cell lines. In vivo evaluation of anti-cancer activity performed in albino mice bearing Dalton's ascites carcinoma showed that the new analogs enhanced life span and prevented increases in body weight owing to tumor volumes. Moreover, cell-cycle analysis and Hoechst staining analysis proved the apoptotic potential of these analogs. Preliminary pharmacokinetic evaluation was carried out on the synthesized compounds to determine the lipophilicity and pKa. Lipophilicity was determined using high-performance liquid chromatography and the results showed a direct correlation between the observed anti-cancer activity and log P value, while pKa values indicated the ionizing range which is a prediction tool for solubility and permeability. PMID- 26369710 TI - The Influence of Respondent Characteristics on the Validity of Self-Reported Survey Responses. AB - OBJECTIVE: To examine concordance between member self-reports and the organization's administrative claims data for two key health factors: number of chronic conditions, and number of prescription drugs. DATA: Medicare Advantage plan claims data and member survey data from 2011 to 2012. DESIGN: Mailed surveys to 15,000 members, enrolled minimum 6 months, drawn from a random sample of primary care physician practices with at least 200 members. METHODS: Descriptive statistics were generated for extent of concordance. Multivariable logistic regressions were used to analyze the association of selected respondent characteristics with likelihood of concordance. FINDINGS: Concordance for number of chronic conditions was 58.4 percent, with 27.3 percent under-reporting, 14.2 percent over-reporting. Concordance for number of prescription drugs was 56.6 percent with 38.9 percent under-reporting, 4.5 percent over-reporting. Number of prescriptions and assistance in survey completion were associated with higher likelihood of concordance for chronic conditions. Assistance in survey completion and number of chronic conditions were associated with higher concordance, and age and number of prescriptions were associated with lower concordance, for prescription drugs. CONCLUSIONS: Self-reported number of chronic conditions and prescription medications are not in high concordance with claims data. Health care researchers and policy makers using patient self-reported data should be aware of these potential biases. PMID- 26369711 TI - In vitro susceptibility of recent Chlamydia trachomatis clinical isolates to the CtHtrA inhibitor JO146. AB - The present study aimed to establish if a previously identified Chlamydia trachomatis HtrA (CtHtrA) inhibitor, JO146, is effective against currently circulating clinical isolates to validate if CtHtrA is a clinically relevant target for future therapeutic development. Inhibition of CtHtrA during the middle of the chlamydial replicative cycle until the completion of the cycle resulted in loss of infectious progeny for six unique clinical isolates representing different serovars. This supports the potential for CtHtrA to be a clinically relevant target for development of new therapeutics and suggests the importance of further investigation of JO146 as a lead compound. PMID- 26369712 TI - Paracoccidioides brasiliensis induces recruitment of alpha3 and alpha5 integrins into epithelial cell membrane rafts, leading to cytokine secretion. AB - Paracoccidioides brasiliensis is one of the etiological agents of paracoccidioidomycosis, a human systemic mycosis, highly prevalent in Latin America. In the present work, we demonstrate that P. brasiliensis yeasts promote IL-6 and IL-8 secretion by the human lung epithelial cell line A549 in an integrin-dependent manner. In fact, small interfering RNA directed to alpha3 and alpha5 integrins decreased IL-6 and IL-8 levels in P. brasiliensis-infected A549 cell cultures. This fungus also led to an increase in the expression of alpha3 and alpha5 integrins in this epithelial cell line. In addition, P. brasiliensis yeasts promoted alpha3 and alpha5 integrins clustering into A549 cell membrane rafts. Furthermore, epithelial cell membrane raft disruption with nystatin decreased IL-6 and IL-8 levels in P. brasiliensis-A549 cell cultures. Therefore, by increasing host alpha3 and alpha5 integrins levels and clustering these receptors into membrane rafts, P. brasiliensis yeasts may modulate host inflammation. PMID- 26369713 TI - Cryptococcal transmigration across a model brain blood-barrier: evidence of the Trojan horse mechanism and differences between Cryptococcus neoformans var. grubii strain H99 and Cryptococcus gattii strain R265. AB - Cryptococcus neoformans (Cn) and Cryptococcus gattii (Cg) cause neurological disease and cross the BBB as free cells or in mononuclear phagocytes via the Trojan horse mechanism, although evidence for the latter is indirect. There is emerging evidence that Cn and the North American outbreak Cg strain (R265) more commonly cause neurological and lung disease, respectively. We have employed a widely validated in vitro model of the BBB, which utilizes the hCMEC/D3 cell line derived from human brain endothelial cells (HBEC) and the human macrophage-like cell line, THP-1, to investigate whether transport of dual fluorescence-labelled Cn and Cg across the BBB occurs within macrophages. We showed that phagocytosis of Cn by non-interferon (IFN)-gamma stimulated THP-1 cells was higher than that of Cg. Although Cn and Cg-loaded THP-1 bound similarly to TNF-activated HBECs under shear stress, more Cn-loaded macrophages were transported across an intact HBEC monolayer, consistent with the predilection of Cn for CNS infection. Furthermore, Cn exhibited a higher rate of expulsion from transmigrated THP-1 compared with Cg. Our results therefore provide further evidence for transmigration of both Cn and Cg via the Trojan horse mechanism and a potential explanation for the predilection of Cn to cause CNS infection. PMID- 26369715 TI - Innate immunity in tuberculosis: how the sensing of mycobacteria and tissue damage modulates macrophage death. AB - The success of Mycobacterium tuberculosis as a human pathogen has been attributed to the ability of the bacillus to proliferate inside macrophages and to induce cell death. This review describes how the sensors of the innate immune system modulate the cell death pathways in infected macrophages and, consequently, the pathogenesis of tuberculosis. PMID- 26369714 TI - Dendrimer-enabled transformation of Anaplasma phagocytophilum. AB - Anaplasma phagocytophilum is an obligate intracellular bacterium that causes the emerging infection, granulocytic anaplasmosis. While electroporation can transform A. phagocytophilum isolated from host cells, no method has been developed to transform it while growing inside the ApV (A. phagocytophilum occupied vacuole). Polyamidoamine (PAMAM) dendrimers, well-defined tree-branched macromolecules used for gene therapy and nucleic acid delivery into mammalian cells, were recently shown to be effective in transforming Chlamydia spp. actively growing in host cells. We determined if we could adapt a similar system to transform A. phagocytophilum. Incubating fluorescently labeled PAMAM dendrimers with infected host cells resulted in fluorescein-positive ApVs. Incubating infected host cells or host cell-free A. phagocytophilum organisms with dendrimers complexed with pCis GFPuv-SS Himar A7 plasmid, which carries a Himar1 transposon cassette encoding GFPuv and spectinomycin/streptomycin resistance plus the Himar1 transposase itself, resulted in GFP-positive, antibiotic resistant bacteria. Yet, transformation efficiencies were low. The transformed bacterial populations could only be maintained for a few passages, likely due to random Himar1 cassette-mediated disruption of A. phagocytophilum genes required for fitness. Nonetheless, these results provide proof of principle that dendrimers can deliver exogenous DNA into A. phagocytophilum, both inside and outside of host cells. PMID- 26369716 TI - Paleomicrobiology of Bartonella infections. AB - Studying ancient infectious diseases is a challenge, as written contemporary descriptions, when available, are often imprecise and do not allow for accurate discrimination among the pathogens endemic at that time. Paleomicrobiology offers a unique access to the history of these infections by identifying precisely the causative agents. Body louse-transmitted infections are amongst the most epidemic diseases in history, especially in war and famine periods. Of these, Bartonella quintana was detected by suicide PCR in 4000-year-old human remains, thus representing the oldest evidence to date of an arthropod-transmitted infection to human beings. This species has also been detected in human specimens from the 11th to 15th, 18th and 19th centuries. In addition, Bartonella henselae, a cat- and flea-associated pathogen, was detected in cat specimens from the 13th to 18th centuries, therefore demonstrating an association of the bacterium and its reservoir for over 800 years. Therefore, pathogenic Bartonella species have been involved in several outbreaks in the past millennia and should systematically be investigated in human remains from suspected epidemics. PMID- 26369718 TI - MicroRNAs in ALS: small pieces to the puzzle. PMID- 26369717 TI - Acetyl-ed question in mitochondrial biology? PMID- 26369719 TI - Effectiveness of Endoscopic Surgery for Comatose Patients with Large Supratentorial Intracerebral Hemorrhages. AB - To evaluate the effectiveness of endoscopic surgery for life-threatening large brain hemorrhage, we reviewed our empirical cases of comatose patients with large supratentorial intracerebral hemorrhage. Among 35 patients with putaminal or subcortical hemorrhage that was evacuated endoscopically, 14 cases (40%) presented both findings of neurological grade IV for severity and hematoma volume exceeding 70 mL in the recent 3 years (endoscope group), whereas 8 cases with the same conditions were treated by conventional craniotomy for the preceding 3-year period (craniotomy group). Between these two groups, mean age was higher and duration of surgery was shorter in the endoscope group, but no significant differences in hematoma size or evacuation rate were recognized. In the 10 cases that presented with signs of cerebral herniation (neurological grade IVb) and required emergent decompression, the preparation time for surgery tended to be shorter in the endoscope group, although the difference was not significant. Additional ventricular drainage was performed in 7 cases and showed a supplemental effect of reducing intracranial pressure (ICP). Consequently, all patients in the endoscope group were rescued without decompressive large craniectomy, even with symptoms of cerebral herniation. In conclusion, endoscopic surgery has the potential to offer an effective therapeutic option for comatose patients with large supratentorial intracerebral hemorrhages, matching conventional craniotomy for emergent treatment in terms of mortality and management of ICP. PMID- 26369720 TI - Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) as a Cognitive Evaluation Tool for Patients with Normal Pressure Hydrocephalus. AB - External lumbar drainage (ELD) is recognized as a screening method for ventriculo peritoneal shunting (VPS) candidacy for possible normal pressure hydrocephalus (NPH). This study focused on the ELD predictability of the cognitive outcome after VPS for NPH. In addition, Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was examined in ELD cognition screening. ELD results were considered positive with any improvement in gait and/or cognition. Among 36 patients examined for possible NPH, 26 underwent VPS because of positive ELD. Cognitive outcome after VPS was assessed at 6-month follow-up. The RBANS scores, examined pre- and post-ELD, were evaluated statistically to identify consistency with the neuropsychologist judgment and the predictability of cognitive outcome after VPS. Among 26 shunted patients, gait was improved in 24. Cognitive improvement was rated in 19, and there were 9 false negative and 5 false positive in ELD cognition screening. The neuropsychologist judgment in ELD cognition screening is most consistent with the RBANS score in delayed memory. The patients rated as improved in cognition after VPS had significantly lower RBANS scores pre-ELD in immediate memory and delayed memory. If both scores at pre-ELD were <= 80 (13 patients), all were rated as improved in cognition after VPS. ELD screening was highly predictive of clinical gait improvement but not of cognitive improvement after VPS for possible NPH. Particularly among patients with a positive ELD gait response, pre-ELD low RBANS scores in memory predicted cognitive improvement after VPS. RBANS seems effective in evaluating cognition for NPH. PMID- 26369721 TI - Outcomes of Oculomotor Nerve Palsy Caused by Internal Carotid Artery Aneurysm: Comparison between Microsurgical Clipping and Endovascular Coiling. AB - The purpose of this study was to compare the clinical outcomes of microsurgical clipping and endovascular coiling in patients with oculomotor nerve palsy (ONP) caused by internal carotid artery (ICA) aneurysm. Among 17 patients with ICA aneurysms presented with ONP, 9 (52.9%) underwent microsurgical clipping and 8 (47.1%) underwent endovascular coiling. Outcomes of functional recovery of ONP were investigated and compared between surgical group and endovascular group. Mean intervals between the onset and treatment were significantly longer in microsurgical group (18.2 days) than in endovascular group (3.5 days). In microsurgical group, complete resolution (CR) of ONP was obtained in 7 of 9 patients (77.8%) and partial resolution (PR) was seen in 2 patients (22.2%). In endovascular group, CR was obtained in 5 of 8 patients (62.5%) and PR was seen in 3 patients (37.5%). The optimal treatment of aneurysm-induced ONP remains controversial; however, present study suggests both procedures are beneficial for achieving functional recovery of ONP. The treatment strategy should be decided primarily considering the general risks of the two procedures, and presence of ONP is not a disadvantageous factor for either procedure. PMID- 26369722 TI - Time-dependent localization of high- and low-sulfated keratan sulfates in the song nuclei of developing zebra finches. AB - Keratan sulfate proteoglycans (KSPGs) and chondroitin sulfate proteoglycans (CSPGs) consist of a protein core with covalently attached glycosaminoglycan side chain. Although CSPGs are known to regulate the end of the critical period, the role of KSPGs in brain development remains unclear. Young male zebra finches memorise song templates during development. The brain regions that are responsible for song learning, known as song nuclei, are recognized as a suitable model for the study of brain development. To understand the potential role of KSPGs, here we examined the localization of KSs with different degrees of sulfation in the brain of developing male zebra finches. Exclusively in the song nuclei, an increase in expression of 5-D-4-positive (5-D-4(+)) high-sulfated KS started after hatching, and reached a plateau at the end of the sensory period, during which the young bird listens to and memorises the song of an adult tutor. By contrast, weak and ubiquitous expression of BCD-4(+) low-sulfated KS remained unchanged until the end of the sensory period, and first increased in the song nuclei at the end of the sensorimotor period, during which the young bird produces plastic songs. Immunoblot analysis showed that phosphacan was a common core protein of 5-D-4(+) KS and BCD-4(+) KS. Finally, we confirmed that the sulfotransferase responsible for the synthesis of high-sulfated KS was exclusively localised in the song nuclei. Our observations suggest that time dependent localization of KSPGs with different sulfation patterns in the song nuclei may underlie song learning in developing male zebra finches. PMID- 26369723 TI - A knot polymer mediated non-viral gene transfection for skin cells. AB - A knot polymer, poly[bis(2-acryloyl)oxyethyl disulphide-co-2-(dimethylamino) ethyl methacrylate] (DSP), was synthesized, optimized and evaluated as a non viral vector for gene transfection for skin cells, keratinocytes. With recessive dystrophic epidermolysis bullosa keratinocytes (RDEBK-TA4), the DSP exhibited high transfection efficacy with both Gaussia luciferase marker DNA and the full length COL7A1 transcript encoding the therapeutic type VII collagen protein (C7). The effective restoration of C7 in C7 null-RDEB skin cells indicates that DSP is promising for non-viral gene therapy of recessive dystrophic epidermolysis bullosa (RDEB). PMID- 26369724 TI - Prostate cancer: Analysing prostate cancer biomarkers in voided urine. PMID- 26369725 TI - Therapy: Continuous testosterone is beneficial. PMID- 26369726 TI - Prostate cancer: AS--contemplation, not intervention. PMID- 26369727 TI - Risk factors: Cholesterol level correlates with PSA level in white but not black men. PMID- 26369728 TI - The plasticity of social emotions. AB - Social emotions such as empathy or compassion greatly facilitate our interactions with others. Despite the importance of social emotions, scientific studies have only recently revealed functional neural plasticity associated with the training of such emotions. Using the framework of two antagonistic neural systems, the threat and social disconnection system on the one hand, and the reward and social connection system on the other, this article describes how training compassion and empathy can change the functioning of these systems in a targeted manner. Whereas excessive empathic sharing of suffering can increase negative feelings and activations in the insula and anterior cingulate cortex (corresponding to the threat and social disconnection system), compassion training can strengthen positive affect and neural activations in the medial orbitofrontal cortex and striatum (corresponding to the reward and social connection system). These neuroimaging findings are complemented by results from behavioral studies showing that compassion is linked to helping and forgiveness behavior, whereas empathic distress not only decreases helping behavior, but is even associated with increased aggressive behavior. Taken together, these data provide encouraging evidence for the plasticity of adaptive social emotions with wide-ranging implications for basic science and applied settings. PMID- 26369730 TI - Our changing neurointerventional world. PMID- 26369729 TI - An insight into the sialome of the horse fly, Tabanus bromius. AB - Blood feeding animals face their host's defenses against tissue injury and blood loss while attempting to feed. One adaptation to surmount these barriers involves the evolution of a salivary potion that disarms their host's inflammatory and anti-hemostatic processes. The composition of the peptide moiety of this potion, or sialome (from the Greek sialo = saliva), can be deducted in part by proper interpretation of the blood feeder' sialotranscriptome. In this work we disclose the sialome of the blood feeding adult female Tabanus bromius. Following assembly of over 75 million Illumina reads (101 nt long) 16,683 contigs were obtained from which 4078 coding sequences were extracted. From these, 320 were assigned as coding for putative secreted proteins. These 320 contigs mapped 85% of the reads. The antigen-5 proteins family was studied in detail, indicating three Tabanus specific clades with and without disintegrin domains, as well as with and without leukotriene binding domains. Defensins were also detailed; a clade of salivary tabanid peptides was found lacking the propeptide domain ending in the KR dipeptide signaling furin cleavage. Novel protein families were also disclosed. Viral transcripts were identified closely matching the Kotonkan virus capsid proteins. Full length Mariner transposases were also identified. A total of 3043 coding sequences and their protein products were deposited in Genbank. Hyperlinked excel spreadsheets containing the coding sequences and their annotation are available at http://exon.niaid.nih.gov/transcriptome/T_bromius/Tbromius-web.xlsx (hyperlinked excel spreadsheet, 11 MB) and http://exon.niaid.nih.gov/transcriptome/T_bromius/Tbromius-SA.zip (Standalone excel with all local links, 360 MB). These sequences provide for a platform from which further proteomic studies may be designed to identify salivary proteins from T. bromius that are of pharmacological interest or used as immunological markers of host exposure. PMID- 26369731 TI - Polyvinylidene fluoride molecules in nanofibers, imaged at atomic scale by aberration corrected electron microscopy. AB - Atomic scale features of polyvinylidene fluoride molecules (PVDF) were observed with aberration corrected transmission electron microscopy. Thin, self-supporting PVDF nanofibers were used to create images that show conformations and relative locations of atoms in segments of polymer molecules, particularly segments near the surface of the nanofiber. Rows of CF2 atomic groups, at 0.25 nm intervals, which marked the paths of segments of the PVDF molecules, were seen. The fact that an electron microscope image of a segment of a PVDF molecule depended upon the particular azimuthal direction, along which the segment was viewed, enabled observation of twist around the molecular axis. The 0.2 nm side-by-side distance between the two fluorine atoms attached to the same carbon atom was clearly resolved. Morphological and chemical changes produced by energetic electrons, ranging from no change to fiber scission, over many orders of magnitude of electrons per unit area, promise quantitative new insights into radiation chemistry. Relative movements of segments of molecules were observed. Promising synergism between high resolution electron microscopy and molecular dynamic modeling was demonstrated. This paper is at the threshold of growing usefulness of electron microscopy to the science and engineering of polymer and other molecules. PMID- 26369732 TI - Establishment of a European Registry for hidradenitis suppurativa/acne inversa by using an open source software. PMID- 26369733 TI - Potentiometric and spectroscopic studies on the copper(II) complexes of rat amylin fragments. The anchoring ability of specific non-coordinating side chains. AB - Copper(ii) complexes of peptides modelling the sequence of the 17-22 residues of rat amylin have been studied by potentiometric, UV-Vis, CD and ESR spectroscopic methods. The peptides were synthesized in N-terminally free forms, NH2-VRSSNN NH2, NH2-VRSSAA-NH2, NH2-VRAANN-NH2, NH2-VRSS-NH2, NH2-SSNN-NH2, NH2-SSNA-NH2 and NH2-AANN-NH2, providing a possibility for the comparison of the metal binding abilities of the amino terminus and the -SSNN- domain. The amino terminus was the primary ligating site in all cases and the formation of only mononuclear complexes was obtained for the tetrapeptides. The thermodynamic stability of the (NH2, N(-), N(-)) coordinated complexes was, however, enhanced by the asparaginyl moiety in the case of NH2-SSNN-NH2, NH2-SSNA-NH2 and NH2-AANN-NH2. Among the hexapeptides the formation of dinuclear complexes was characteristic for NH2 VRSSNN-NH2 demonstrating the anchoring ability of the -SSNN- (SerSerAsnAsn) domain. The complexes of the heptapeptide NH2-GGHSSNN-NH2 were also studied and the data supported the above mentioned anchoring ability of the -SSNN- site. PMID- 26369734 TI - Transcriptomic variation of hepatopancreas reveals the energy metabolism and biological processes associated with molting in Chinese mitten crab, Eriocheir sinensis. AB - Molting is a critical developmental process for crustaceans, yet the underlying molecular mechanism is unknown. In this study, we used RNA-Seq to investigate transcriptomic profiles of the hepatopancreas and identified differentially expressed genes at four molting stages of Chinese mitten crab (Eriocheir sinensis). A total of 97,398 transcripts were assembled, with 31,900 transcripts annotated. Transcriptomic comparison revealed 1,189 genes differentially expressed amongst different molting stages. We observed a pattern associated with energy metabolism and physiological responses during a molting cycle. In specific, differentially expressed genes enriched in postmolt were linked to energy consumption whereas genes enriched in intermolt were related to carbohydrates, lipids metabolic and biosynthetic processes. In premolt, a preparation stage for upcoming molting and energy consumption, highly expressed genes were enriched in response to steroid hormone stimulus and immune system development. The expression profiles of twelve functional genes detected via RNA Seq were corroborated through real-time RT-PCR assay. Together, our results, including assembled transcriptomes, annotated functional elements and enriched differentially expressed genes amongst different molting stages, provide novel insights into the functions of the hepatopancreas in energy metabolism and biological processes pertaining to molting in crustaceans. PMID- 26369735 TI - Multivariate selection drives concordant patterns of pre- and postcopulatory sexual selection in a livebearing fish. AB - In many species, females mate with multiple partners, meaning that sexual selection on male traits operates across a spectrum that encompasses the competition for mates (that is, before mating) and fertilizations (after mating). Despite being inextricably linked, pre- and postcopulatory sexual selection are typically studied independently, and we know almost nothing about how sexual selection operates across this divide. Here we bridge this knowledge gap using the livebearing fish Poecilia reticulata. We show that both selective episodes, as well as their covariance, explain a significant component of variance in male reproductive fitness. Moreover, linear and nonlinear selection simultaneously act on pre- and postcopulatory traits, and interact to generate multiple phenotypes with similar fitness. PMID- 26369736 TI - Impact on survival of addition of etoposide to primary chemotherapy in diffuse large B-cell lymphoma: a Swedish Lymphoma Registry study. AB - No randomised study in the rituximab era has been performed specifically to evaluate addition of etoposide to treatment of diffuse large B-cell lymphoma (DLBCL). The aim of this study was to compare the outcome with three chemotherapy regimens (R-CHOP-21, R-CHOP-14 and R-CHOEP-14) in a population-based cohort in terms of overall survival, adjusted for clinical prognostic factors. Through the Swedish Lymphoma Registry, 3443 patients with DLBCL were identified 2007-2012. Among all patients, there was no evidence of a difference between the regimens, after adjustment for prognostic factors. However, when restricted to patients aged up to 65, R-CHOEP-14 was associated with superior outcome compared to both R CHOP-21 (hazard ratio: 0.49, 95% confidence interval: 0.3-0.9, p = 0.028) and R CHOP-14 (hazard ratio: 0.64, 95% confidence interval: 0.4-1.0, p = 0.06), when adjusted for prognostic factors. Results were consistent in an additional stratified analysis with patients grouped according to age and IPI-score. In conclusion, we could show that R-CHOEP-14 was associated with superior overall survival in patients with DLBCL aged up to 65 years, indicating that this may be a valid treatment option for this patient population. To further investigate which patient groups that may benefit the most from treatment intensification, R CHOEP-14 should be compared to R-CHOP-21 in a randomised setting. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26369737 TI - Pulmonary hypertension is an independent predictor of cardiovascular events and mortality in haemodialysis patients. AB - AIM: The evidence about prevalence, associated factors of pulmonary hypertension (PH) and its impact on patient's outcomes is limited. METHODS: We included 211 haemodialysis patients, we estimated the systolic pulmonary artery pressure (SPAP) by 2D Doppler echocardiography defining PH as a SPAP above 35 mmHg, the median follow-up was 39 (19-56) moths, and the primary endpoints were all cause mortality and cardiovascular events. RESULTS: We found PH in 91 patients (43.9%). Independent determinants of PH were age, previous cardiovascular disease, the Nt pro-BNP level hs-TnT, the systolic dysfunction, diastolic dysfunction and left ventricular hypertrophy. Over the follow-up 94 cardiovascular events occurred, variables associated were: PH, age, history cardiovascular disease, dyslipidaemia, elevated concentration of Nt-pro-BNP and hs-TnT, systolic and diastolic dysfunction, in a multivariate model, the PH maintained its independent association. Mortality data: 88 patients died (41.7%); 35 (29.5%) in the no PH group and 53 (58.5%) in the PH group (P < 0.001). In the Cox survival analysis, we found an association between mortality and age, previous cardiovascular disease, history of peripheral vascular disease, Nt-pro-BNP levels. In a multivariate model the PH remains as independent predictor of mortality. CONCLUSIONS: Pulmonary hypertension is a common finding in HD patients and a valuable predictor of mortality and cardiovascular events. Prospective studies are needed to assess the effect of intervention on risk factors in improving patient's outcomes. PMID- 26369738 TI - [Advanced practice nursing advances]. PMID- 26369739 TI - [Role and missions of the mobile wound healing team]. AB - The actions carried out by the mobile wounds and cicatrisation team of Bordeaux university hospital help to harmonise professional practices, with benefits for the hospital, the caregivers and the patients. Within the team, this "mentoring system" also strengthens the expertise of individual nurses. The results obtained over the last two years show that the scheme provides real added value in terms of the quality of care, in a context of a constant search for efficiency. PMID- 26369740 TI - [The professional mobility of hospital nurses]. AB - For several decades, hospitals have been faced with the voluntary departures of nurses. In parallel to this external mobility, internal mobility is also on the rise and is not always initiated by the nurse. This new mode of management has repercussions for professionals, patients as well as for the quality of care. PMID- 26369741 TI - [Head and neck cancers. A path of complex treatments]. PMID- 26369742 TI - [Epidemiology, diagnosis and treatment of head and neck cancers]. AB - Cancers of the upper aerodigestive tracts are the fourth most common cancer in France. The main risk factors are smoking and alcohol. They do not necessarily present specific signs, making their early diagnosis difficult. A change in the patient's general condition is a late sign leading to a poor prognosis of the disease. PMID- 26369743 TI - [The diagnostic nurse consultation in head and neck oncology]. AB - The diagnosis announcement nurse consultation is carried out with the patient and/or their family. It is a time of exchange, listening and sharing of information. The diagnosis announcement nurse is available to answer questions from the patient and their family about the disease, the treatments and the follow-up care. PMID- 26369744 TI - [Nursing care in reconstructive surgery in cases of head and neck cancer]. AB - The treatment of cancers of the upper aerodigestive tract favours an organ- and function- preserving surgical approach. The nursing care draws on multiple skills, on both a technical and educational level, in order to assure global patient management. PMID- 26369745 TI - [Post-radiotherapy care and monitoring of head and neck cancers]. AB - Radiotherapy performed to treat head and neck cancer results in considerable side effects and the patient must be provided with all the necessary information and regular monitoring. From the announcement of the diagnosis, during and after the radiotherapy, the nurse coordinator identifies and assesses the needs, expectations and concerns of the patients. Their role helps to simplify and personalise the care pathway, providing a liaison between the different professionals and offering support for the patient. PMID- 26369746 TI - [Nursing care for tracheotomy and tracheostomy patients]. AB - Nursing care is specific in otorhinolaryngology, particularly in oncology. The three dimensions of the care, technical, relational and educational, are essential and reflect the quality of the patient management which must be multi disciplinary. PMID- 26369747 TI - [Psychological care of patients with head and neck cancer]. AB - Treatments for head and neck cancers are generally complex and debilitating. Surgery, often mutilating, profoundly affects the relationship between oneself and others and causes verbal communication, breathing and swallowing difficulties. The functional and aesthetic sequelae are a constant reminder to the patient of the disease and make them conscious of their appearance. PMID- 26369748 TI - [Support at home for a patient with cancer of the jaw]. AB - Home care presents specific difficulties. The support of Ms. C, suffering from a malignant tumour of the lower jaw illustrates a difficult care context due to a painful and poorly-healing wound, low self-esteem and communication difficulties. Maintaining the right distance and providing professional support are therefore essential in order to give high quality care to this patient. PMID- 26369749 TI - [Progress in head and neck cancer]. PMID- 26369750 TI - [Delegation in private practice]. PMID- 26369751 TI - Clinical features, exercise hemodynamics, and determinants of left ventricular elevated filling pressure in heart-transplanted patients. AB - This study aimed to assess clinical, functional, and hemodynamic characteristics of heart-transplanted (HTX) patients during exercise. We performed comprehensive echocardiographic graft function assessment during invasive hemodynamic semi supine exercise test in 57 HTX patients. According to hemodynamics findings, patients were divided into Group A: normal left ventricular (LV) filling pressure (FP): pulmonary capillary wedge pressure (PCWP) <15 mmHg at rest and <25 mmHg at peak exercise, and Group B: elevated LV-FP: PCWP >=15 mmHg at rest or >=25 mmHg at peak exercise. Thirty-one patients (54%) had normal LV-FP and 26 patients (46%) had elevated LV-FP. The latter had higher cumulative rejection burden (P < 0.01) and were more symptomatic (NYHA class >1) (P < 0.05), and cardiac allograft vasculopathy (CAV) was more prevalent (P < 0.05). With exercise, the changes in both left- and right-sided filling pressures were significantly increased, whereas LV longitudinal myocardial deformation was lower (P < 0.05) in patients with elevated LV-FP than in patients with normal LV-FP. No between-group difference was observed for cardiac index or LV ejection fraction (LVEF) during exercise. In conclusion, elevated LV-FP can be demonstrated in approximately 50% of HTX patients. Patients with elevated LV-FP have impaired myocardial deformation capacity, higher prevalence of CAV, and higher rejection burden, and were more symptomatic. Exercise test with the assessment of longitudinal myocardial deformation should be considered in routine surveillance of HTX patients as a marker of restrictive filling (ClinicalTrials.gov Identifier: NCT02077764). PMID- 26369752 TI - Feasibility and preliminary outcomes of fetoscopic laser photocoagulation for monochorionic twin gestation with selective intrauterine growth restriction accompanied by severe oligohydramnios. AB - AIM: This study aimed to clarify the feasibility and perinatal outcomes of fetoscopic laser photocoagulation (FLP) for monochorionic twin gestation with selective intrauterine growth restriction (sIUGR) accompanied by both abnormal umbilical artery Doppler waveforms and isolated severe oligohydramnios of the sIUGR twin. METHODS: In this prospective clinical trial, which included 10 cases with absent or reversed end-diastolic flow in the umbilical artery and severe oligohydramnios of the sIUGR twin, the main outcomes investigated were the feasibility of FLP and the rate of severe FLP-related maternal complications. The survival rate and incidence of neurological abnormalities of the twins at 28 days of age were also evaluated. RESULTS: FLP was completed for all cases without major intraoperative maternal complications, although one case experienced threatened preterm labor requiring intensive treatment after the procedure. Three sIUGR and 10 larger twins were alive without neurological abnormalities at 28 days of age, while intrauterine fetal death occurred in the remaining seven sIUGR twins. CONCLUSION: FLP for monochorionic twins with sIUGR, especially when accompanied by abnormal Doppler and severe oligohydramnios of the sIUGR twin, appears to be feasible and potentially beneficial for the larger twin, as well as for some sIUGR twins. PMID- 26369753 TI - Efficacy of once-weekly dapsone dosing for Pneumocystis jirovecii pneumonia prophylaxis post transplantation. AB - BACKGROUND: Pneumocystis jirovecii pneumonia (PCP) remains a concern after organ transplantation. In 2005, the University of Kentucky (UK) Transplant Center implemented a novel dosing regimen of weekly dapsone as an alternative for patients with contraindications or intolerability to trimethoprim sulfamethoxazole (TMP-SMZ), which remains the drug of choice. The purpose of this study was to compare the efficacy of weekly dapsone with TMP-SMZ in preventing PCP post transplantation. METHODS: A single-center, cohort, retrospective review of kidney and liver transplant patients from January 2005 to December 2012 was conducted. Patients who were identified as dapsone cases were matched in a 1:1 ratio with TMP-SMZ controls based on type of transplant, age, primary diagnosis, and gender. The primary endpoint assessed was the diagnosis of PCP at 6 and 12 months post transplant. RESULTS: A total of 158 patients were included in the study. No documented cases of PCP occurred in either study group at 6 or 12 months (P = 1.0). In dapsone patients 35 (44%) cases of breakthrough infection occurred, compared to 24 (30%) in the TMP-SMZ group (P = 0.07) within 12 months post transplant. In the dapsone group, 52 (65%) patients were hospitalized within 6 months post transplant compared to 36 (46%) patients in the TMP-SMZ group (P = 0.01). Similar results were seen in patients hospitalized within 12 months post transplant; 49% of patients were switched from TMP-SMZ to dapsone owing to renal dysfunction. CONCLUSION: No documented cases of PCP occurred in either study group. Future studies are warranted to show the efficacy of weekly dapsone dosing compared to other PCP prophylaxis regimens. PMID- 26369754 TI - MR-based in vivo follow-up study of Achilles tendon volume and hydration state after ankle-loading activity. AB - The purpose of this study was to evaluate temporal alterations of the Achilles tendon volume and hydration state after cross-country-running. Achilles tendons of six untrained participants were examined on a 3T MR-scanner before running, immediately afterwards, and in the following 24, 48, and 72 h. Using a 3D-UTE sequence, caudal (CA) and cranial (CR) mid-portion tendon areas were examined with off-resonance saturation ratios (OSR) and T2* relaxation times. Tendon volume was measured with a self-written Matlab-based automated contour detection algorithm (AVAT) in submillimeter T2-weighted MR images. A significant influence of running in caudal (P = 0.017) and cranial OSR values (P = 0.001), tendon volume (P = 0.024), and cranial T2* measurements (P = 0.046), but not in caudal T2* values (P = 0.298) were found. In detail, mean individual OSR and tendon volume measurements demonstrated a similar but inverted course in their values after exercise: initially, OSR values increased after running (and tendon volume decreased), while subsequently a decrease of OSR values (with an increase of tendon volume) could be observed. OSR and tendon volume measurements are able to detect a physiological response of tendons to a mechanical stimulus. After a transient decrease of free water in the Achilles tendon, an increase with a maximum free water content 48 h after ankle loading and a tendency toward normalization after 72 h was found. PMID- 26369755 TI - Transcriptomics-based strain optimization tool for designing secondary metabolite overproducing strains of Streptomyces coelicolor. AB - In silico model-driven analysis using genome-scale model of metabolism (GEM) has been recognized as a promising method for microbial strain improvement. However, most of the current GEM-based strain design algorithms based on flux balance analysis (FBA) heavily rely on the steady-state and optimality assumptions without considering any regulatory information. Thus, their practical usage is quite limited, especially in its application to secondary metabolites overproduction. In this study, we developed a transcriptomics-based strain optimization tool (tSOT) in order to overcome such limitations by integrating transcriptomic data into GEM. Initially, we evaluated existing algorithms for integrating transcriptomic data into GEM using Streptomyces coelicolor dataset, and identified iMAT algorithm as the only and the best algorithm for characterizing the secondary metabolism of S. coelicolor. Subsequently, we developed tSOT platform where iMAT is adopted to predict the reaction states, and successfully demonstrated its applicability to secondary metabolites overproduction by designing actinorhodin (ACT), a polyketide antibiotic, overproducing strain of S. coelicolor. Mutants overexpressing tSOT targets such as ribulose 5-phosphate 3-epimerase and NADP-dependent malic enzyme showed 2 and 1.8-fold increase in ACT production, thereby validating the tSOT prediction. It is expected that tSOT can be used for solving other metabolic engineering problems which could not be addressed by current strain design algorithms, especially for the secondary metabolite overproductions. PMID- 26369756 TI - Commercially Available Preparations of Recombinant Wnt3a Contain Non-Wnt Related Activities Which May Activate TGF-beta Signaling. AB - The Wnt ligands are a family of secreted signaling proteins which play key roles in a number of cellular processes under physiological and pathological conditions. Wnts bind to their membrane receptors and initiate a signaling cascade which leads to the nuclear localization and transcriptional activity of beta-catenin. The development of purified recombinant Wnt ligands has greatly aided in our understanding of Wnt signaling and its functions in development and disease. In the current study, we identified non-Wnt related signaling activities which were present in commercially available preparations of recombinant Wnt3a. Specifically, we found that treatment of cultured fibroblasts with recombinant Wnt3a induced immediate activation of TGF-beta and BMP signaling and this activity appeared to be independent of the Wnt ligand itself. Therefore, while purified recombinant Wnt ligands continue to be a useful tool for studying this signaling pathway, one must exercise a degree of caution when analyzing the results of experiments that utilize purified recombinant Wnt ligands. PMID- 26369757 TI - Development of an Online Toolkit for Measuring Performance in Health Emergency Response Exercises. AB - INTRODUCTION: Exercises that simulate emergency scenarios are accepted widely as an essential component of a robust Emergency Preparedness program. Unfortunately, the variability in the quality of the exercises conducted, and the lack of standardized processes to measure performance, has limited the value of exercises in measuring preparedness. METHODS: In order to help health organizations improve the quality and standardization of the performance data they collect during simulated emergencies, a model online exercise evaluation toolkit was developed using performance measures tested in over 60 Emergency Preparedness exercises. The exercise evaluation toolkit contains three major components: (1) a database of measures that can be used to assess performance during an emergency response exercise; (2) a standardized data collection tool (form); and (3) a program that populates the data collection tool with the measures that have been selected by the user from the database. The evaluation toolkit was pilot tested from January through September 2014 in collaboration with 14 partnering organizations representing 10 public health agencies and four health care agencies from eight states across the US. Exercise planners from the partnering organizations were asked to use the toolkit for their exercise evaluation process and were interviewed to provide feedback on the use of the toolkit, the generated evaluation tool, and the usefulness of the data being gathered for the development of the exercise after-action report. RESULTS: Ninety-three percent (93%) of exercise planners reported that they found the online database of performance measures appropriate for the creation of exercise evaluation forms, and they stated that they would use it again for future exercises. Seventy-two percent (72%) liked the exercise evaluation form that was generated from the toolkit, and 93% reported that the data collected by the use of the evaluation form were useful in gauging their organization's performance during the exercise. Seventy-nine percent (79%) of exercise planners preferred the evaluation form generated by the toolkit to other forms of evaluations. CONCLUSION: Results of this project show that users found the newly developed toolkit to be user friendly and more relevant to measurement of specific public health and health care capabilities than other tools currently available. The developed toolkit may contribute to the further advancement of developing a valid approach to exercise performance measurement. PMID- 26369758 TI - Survivability and reactivity of glycine and alanine in early oceans: effects of meteorite impacts. AB - Prebiotic oceans might have contained abundant amino acids, and were subjected to meteorite impacts, especially during the late heavy bombardment. It is so far unknown how meteorite impacts affected amino acids in the early oceans. Impact experiments were performed under the conditions where glycine was synthesized from carbon, ammonia, and water, using aqueous solutions containing (13)C-labeled glycine and alanine. Selected amino acids and amines in samples were analyzed with liquid chromatography-mass spectrometry (LC/MS). In particular, the (13)C labeled reaction products were analyzed to distinguish between run products and contaminants. The results revealed that both amino acids survived partially in the early ocean through meteorite impacts, that part of glycine changed into alanine, and that large amounts of methylamine and ethylamine were formed. Fast decarboxylation was confirmed to occur during such impact processes. Furthermore, the formation of n-butylamine, detected only in the samples recovered from the solutions with additional nitrogen and carbon sources of ammonia and benzene, suggests that chemical reactions to form new biomolecules can proceed through marine impacts. Methylamine and ethylamine from glycine and alanine increased considerably in the presence of hematite rather than olivine under similar impact conditions. These results also suggest that amino acids present in early oceans can contribute further to impact-induced reactions, implying that impact energy plays a potential role in the prebiotic formation of various biomolecules, although the reactions are complicated and depend upon the chemical environments as well. PMID- 26369759 TI - Hepatitis C knowledge among gay and other homosexually active men in Australia. AB - INTRODUCTION AND AIMS: Gay and other homosexually active men (hereafter 'gay men') are at elevated risk of becoming infected with hepatitis C virus (HCV) via injecting drug use and sexual risk practices. This paper aimed to measure HCV knowledge among gay men in Australia and whether knowledge differed according to HCV risk. DESIGN AND METHODS: In 2013, a cross-sectional, online survey of 405 Australian gay men explored the social aspects of HCV. Bivariate and multivariate linear regressions were used to examine factors associated with higher HCV knowledge. RESULTS: The mean age of respondents was 39.2 years (SD = 13.3), and most men (75.3%) were born in Australia. According to self-report, 32.1% were HIV positive, 3.0% were HCV-positive and 8.9% were HIV/HCV co-infected. The mean number of correct HCV knowledge items was 8.2 (SD = 3.9; range 0-15). In a multivariate analysis, higher HCV knowledge was associated with higher educational attainment, being HCV-positive, being HIV-positive and injecting drug use. DISCUSSION AND CONCLUSIONS: HCV knowledge among gay men was moderately good, although knowledge of testing, treatment and natural history of HCV was generally quite poor. Encouragingly, higher knowledge was reported among men at highest HCV risk. Viral hepatitis and HIV organisations, together with general practitioners and other health services, should continue to target gay men at a high risk of acquiring HCV with education and health promotion. [Lea T, Hopwood M, Aggleton P. Hepatitis C knowledge among gay and other homosexually active men in Australia. Drug Alcohol Rev 2016;35:477-483]. PMID- 26369760 TI - [Classification of cell-based medicinal products and legal implications: An overview and an update]. AB - In general, cell-based medicinal products do not represent a uniform class of medicinal products, but instead comprise medicinal products with diverse regulatory classification as advanced-therapy medicinal products (ATMP), medicinal products (MP), tissue preparations, or blood products. Due to the legal and scientific consequences of the development and approval of MPs, classification should be clarified as early as possible. This paper describes the legal situation in Germany and highlights specific criteria and concepts for classification, with a focus on, but not limited to, ATMPs and non-ATMPs. Depending on the stage of product development and the specific application submitted to a competent authority, legally binding classification is done by the German Lander Authorities, Paul-Ehrlich-Institut, or European Medicines Agency. On request by the applicants, the Committee for Advanced Therapies may issue scientific recommendations for classification. PMID- 26369761 TI - [Xenogeneic cell therapeutics: Treatment of type 1 diabetes using porcine pancreatic islets and islet cells]. AB - In view of the existing shortage of human donor organs and tissues, xenogeneic cell therapeutics (xCT) offer an alternative for adequate treatment. In particular, porcine pancreatic islets and islet cells have already entered the field of experimental therapy for type-1 diabetes mellitus (T1DM) patients. Thereby, xCT depict challenging products with a glance on medical, ethical, and regulatory questions. With cross-species transplantation (xenotransplantation), the risk of immunological graft rejection as well as the risk of infectious transmission of microbial and viral pathogens must be considered. This includes the bidirectional transmission of microorganisms from graft to host as well as from host to graft. Crossing the border of species requires a critical risk benefit evaluation as well as a thorough longtime surveillance of transplant recipients after treatment. The international legal and regulatory requirements for xCT are inter alia based on the World Health Organization criteria summarized in the Changsha Communique (2008). In the European Union, they were reflected by the European Medicines Agency (EMA) Guideline on Xenogeneic Cell-based Medicinal Products following the implementation of the Regulation on Advanced Therapies (ATMP). On the basis of this regulation, the first non-clinical and clinical experiences were obtained for porcine islets. The results suggest that supportive treatment of T1DM risk patients with xCT may be an alternative to established allogeneic organ transplantation in the future. PMID- 26369762 TI - [Mesenchymal stromal cells in the treatment of graft-versus-host disease: where do we stand?]. AB - Medicinal products based on mesenchymal stromal cells (MSC) are expected to have a therapeutic benefit in a variety of conditions and, accordingly, are being tested in many clinical studies. The treatment and prevention of graft-versus host disease (GVHD) is one of the world's most widely studied MSC therapy concepts. So far, one MSC medicinal product has been approved for the treatment of GvHD. This article gives an overview of the particular features related to the production of MSC-based medicinal products, the state of non-clinical research, and the clinical development status of MSCs and the associated challenges, especially in the context of GvHD. PMID- 26369763 TI - [Scientific advice by the national and European approval authorities concerning advanced therapy medicinal products]. AB - The aim of scientific advice is to support pharmaceutical developers in regulatory and scientific questions, thus facilitating the development of safe and efficacious new medicinal products. Recent years have shown that the development of advanced therapy medicinal products (ATMPs) in particular needs a high degree of regulatory support. On one hand, this is related to the complexity and heterogeneity of this group of medicinal products and on the other hand due to the fact that mainly academic research institutions and small- and medium sized enterprises (SMEs) are developing ATMPs. These often have limited regulatory experience and resources. In 2009 the Paul-Ehrlich-Institut (PEI) initiated the Innovation Office as a contact point for applicants developing ATMPs. The mandate of the Innovation Office is to provide support on regulatory questions and to coordinate national scientific advice meetings concerning ATMPs for every phase in drug development and especially with view to the preparation of clinical trial applications. On the European level, the Scientific Advice Working Party (SAWP) of the Committee for Medicinal Products for Human Use (CHMP) of the European Medicinal Agency (EMA) offers scientific advice. This article describes the concepts of national and EMA scientific advice concerning ATMPs and summarizes the experience of the last six years. PMID- 26369764 TI - [Current concept for the microbiological safety of cell-based medicinal products]. AB - Ensuring microbiological safety in advanced-therapy medicinal products is still a big challenge for manufacturers. There are fundamental problems, especially in cell-based medicinal products, regarding sterility of source materials, short shelf-life of final products, and the selection of suitable microbiological methods. Different from classical medicinal products, there is the need to evaluate a large number of possible risks and to calculate the risk-benefit balance. Depending on the source material, the presence of micro-organisms with specific growth requirements has to be considered. They cannot be detected by conventional testing methods, but may replicate after the application of the preparation in the recipient. Mycoplasmas are the primary representatives of these contaminants and specific testing procedures are required. Additionally, depending on the source and processing of the biological material, specific testing methods for mycobacteria and other contaminants should be included. Alternative microbiological methods (e.g. NAT, flow cytometry) should be applied in order to reduce the time to detection and to provide reliable results before application of a preparation, but should be also assessed for their possible use for the detection of conventionally undetectable micro-organisms. PMID- 26369765 TI - [Regulatory requirements regarding cell-based medicinal products for human and veterinary use - a comparison]. AB - At present, there is no separate regulatory framework for cell-based medicinal products (CBMP) for veterinary use at the European or German level. Current European and national regulations exclusively apply to the corresponding medicinal products for human use. An increasing number of requests for the regulatory classification of CBMP for veterinary use, such as allogeneic stem cell preparations and dendritic cell-based autologous tumour vaccines, and a rise in scientific advice for companies developing these products, illustrate the need for adequate legislation. Currently, advice is given and decisions are made on a case-by-case basis regarding the regulatory classification and authorisation requirements.Since some of the CBMP - in particular in the area of stem-cell products - are developed in parallel for human and veterinary use, there is an urgent need to create specific legal definitions, regulations, and guidelines for these complex innovative products in the veterinary sector as well. Otherwise, there is a risk that that the current legal grey area regarding veterinary medicinal products will impede therapeutic innovations in the long run. A harmonised EU-wide approach is desirable. Currently the European legislation on veterinary medicinal products is under revision. In this context, veterinary therapeutics based on allogeneic cells and tissues will be defined and regulated. Certainly, the legal framework does not have to be as comprehensive as for human CBMP; a leaner solution is conceivable, similar to the special provisions for advanced-therapy medicinal products laid down in the German Medicines Act. PMID- 26369766 TI - Tissue establishment as a necessary institution within the country health care system: importance, requirements and structure. AB - A tissue establishment is a unit or service, inside or outside of a public or private hospital, generally operated by public or non-profit-making bodies or in some countries by private profit-making institutions that procure, process, sterilise, store, and distribute sterilised human tissues to private or public hospitals to be used in certain medical treatments. Each tissue establishment should adopt the best possible structure, hired the necessary well-trained staff, according to the level of its activities, and should establish the necessary internal committees to ensure the highest quality of its operation. In addition, the tissue establishment should adopt a quality management system in order to reduce the risk and maximize the benefits of the transplantation process. PMID- 26369767 TI - Designed nucleases for targeted genome editing. AB - Targeted genome-editing technology using designed nucleases has been evolving rapidly, and its applications are widely expanding in research, medicine and biotechnology. Using this genome-modifying technology, researchers can precisely and efficiently insert, remove or change specific sequences in various cultured cells, micro-organisms, animals and plants. This genome editing is based on the generation of double-strand breaks (DSBs), repair of which modifies the genome through nonhomologous end-joining (NHEJ) or homology-directed repair (HDR). In addition, designed nickase-induced generation of single-strand breaks can also lead to precise genome editing through HDR, albeit at relatively lower efficiencies than that induced by nucleases. Three kinds of designed nucleases have been used for targeted DSB formation: zinc-finger nucleases, transcription activator-like effector nucleases, and RNA-guided engineered nucleases derived from the bacterial clustered regularly interspaced short palindromic repeat (CRISPR)-Cas (CRISPR-associated) system. A growing number of researchers are using genome-editing technologies, which have become more accessible and affordable since the discovery and adaptation of CRISPR-Cas9. Here, the repair mechanism and outcomes of DSBs are reviewed and the three types of designed nucleases are discussed with the hope that such understanding will facilitate applications to genome editing. PMID- 26369768 TI - A systematic review of cognitive performance in patients with childhood craniopharyngioma. AB - Craniopharyngiomas are rare brain tumors of the sellar/suprasellar region, often adversely affecting patients' physical and psychosocial functioning. Until a few years ago, knowledge on cognitive deficits in craniopharyngioma patients was based on little valid evidence, with considerable inconsistencies across studies. Findings from recent research, with partly larger sample sizes, add to existing evidence to provide a more clear and reliable picture. The current review aims to summarize and systemize current findings on cognitive deficits in childhood craniopharyngioma, taking account of patient- and treatment-related variables where possible. Those studies were included that reported results of childhood craniopharyngioma patients tested with formalized neuropsychological tests (irrespective of their age at study, group size >=10). A systematic assignment of test results to subcomponents of broader cognitive domains (e.g. to specific memory systems and processes) allows for a first comprehensive overview of patterns of spared and impaired cognitive functions. We show that episodic memory recall in particular is impaired, largely sparing other memory components. In accordance with recent knowledge on mammillary function, patients with hypothalamic involvement appear to be at particular risk. Deficits in higher cognitive processes, relying on the integrity of the prefrontal cortex and its subcortical pathways, may also occur, but results are still inconsistent. To gain deeper insight into the pattern of deficits and their association with patient- and treatment-related variables, further multi-site research with larger cohorts is needed. PMID- 26369770 TI - [In Process Citation]. PMID- 26369769 TI - Repeated stereotactic radiosurgery for patients with progressive brain metastases. AB - In the present study we have evaluated the efficacy and toxicity of repeated stereotactic radiosurgery (SRS) in patients with recurrent/progressive brain metastases. Between March 2006 and October 2014, 43 patients (21 men and 22 women) with 47 lesions received a second course of SRS given in three daily fractions of 7-8 Gy. With a follow-up study of 19 months, the 1- and 2-year survival rates from repeated SRS were 37 and 20%, respectively, and the 1- and 2 year local control rates were 70 and 60%, respectively. Actuarial local control was significantly better for breast and lung metastases as compared with melanoma metastases; specifically, 1-year local control rates were 38% for melanoma, 78% for breast carcinoma and 73% for non-small cell lung cancer (NSCLC) metastases (p = 0.01). The cause of death was progressive systemic disease in 25 patients and progressive brain disease in 11 patients. Stable extracranial disease (p = 0.01) and Karnofsky performance status (KPS; p = 0.03) were predictive of longer survival. Radiologic changes suggestive of brain radionecrosis were observed in 9 (19%) out of 47 lesions, with an actuarial risk of 34% at 12 months. Neurological deficits (RTOG Grade 2 or 3) associated with brain necrosis occurred in 14% of patients. In conclusion, a second course of SRS given in three daily fractions is a feasible treatment for selected patients with recurrent/progressive brain metastases. Further studies are needed to explore the efficacy and safety of different dose-fractionation schedules, especially in patients with melanoma or large metastases. PMID- 26369771 TI - [A 74 year old patient with recurrent shock caused by hypopituitarism]. AB - This article analyzes the case of a 74 year old patient who was hospitalized four times with recurrent complaints, which consisted of hypothermia, hypotension, weakness, and a hyponatremia, and were always caused by an underlying acute infection. Laboratory results showed an hypothyroidism, a secondary adrenal insufficiency, a secondary hypogonadism, and a growth hormone deficiency, which led to a diagnosis of pituitary dysfunction. Magnetic resonance imaging of the brain showed an 'empty sella', a non-visualization of the pituitary gland caused by an herniation of a supra-sellar cistern into the pituitary fossa. Considering the lack of an underlying pituitary tumor, a treatment consisting of partial hormonal substitution was started, eventually resulting in the full recovery of the patient. PMID- 26369772 TI - Role of Calcium Signaling in B Cell Activation and Biology. AB - Increase in intracellular levels of calcium ions (Ca2+) is one of the key triggering signals for the development of B cell response to the antigen. The diverse Ca2+ signals finely controlled by multiple factors participate in the regulation of gene expression, B cell development, and effector functions. B cell receptor (BCR)-initiated Ca2+ mobilization is sourced from two pathways: one is the release of Ca2+ from the intracellular stores, endoplasmic reticulum (ER), and other is the prolonged influx of extracellular Ca2+ induced by depleting the stores via store-operated calcium entry (SOCE) and calcium release-activated calcium (CRAC) channels. The identification of stromal interaction molecule 1(STIM1), the ER Ca2+ sensor, and Orai1, a key subunit of the CRAC channel pore, has now provided the tools to understand the mode of Ca2+ influx regulation and physiological relevance. Herein, we discuss our current understanding of the molecular mechanisms underlying BCR-triggered Ca2+ signaling as well as its contribution to the B cell biological processes and diseases. PMID- 26369773 TI - Physiologically Based Modelling of Darunavir/Ritonavir Pharmacokinetics During Pregnancy. AB - Pregnant women are usually excluded from clinical trials. Physiologically based pharmacokinetic (PBPK) modelling may provide a method to predict pharmacokinetics in pregnant women, without the need to perform extensive in vivo clinical trials. Here, we used mechanistic modelling to delineate the potential impact of drug transporters on darunavir pharmacokinetics and to identify current knowledge gaps that limit accurate PBPK modelling of darunavir/ritonavir (darunavir/r) exposure in pregnancy. Simcyp (version 13.2) was used for PBPK modelling, using physicochemical and in vitro pharmacokinetic parameters of darunavir and ritonavir from the literature. The Michaelis-Menten constant (K m) and the maximum rate of metabolite formation (V max) for cytochrome P450 3A4-mediated darunavir biotransformation and inhibition by ritonavir were determined experimentally, while the contributions of hepatocyte influx and efflux transporters were assessed by sensitivity analysis. The simulations were compared with previously published clinical pharmacokinetic data. We found that use of a well-stirred liver model overestimated darunavir exposure substantially. A permeability-limited liver model, including hepatic uptake and efflux transporters and an efficient enterohepatic circulation step, resulted in an acceptable description of darunavir/r exposure. For the 600/100 mg darunavir/r twice-daily dose and the 800/100 mg once-daily dose, the estimated pharmacokinetic parameters were within a 2-fold range of the reported data. The predicted decreases in the area under the concentration-time curve (AUC) values during pregnancy for the twice- and once-daily doses were 27 and 41%, respectively, which were in line with the observed decreases of 17-22 and 33%. In conclusion, our data support a clinically relevant role of hepatic transporters in darunavir pharmacokinetics. By including them in our model, we successfully approximated the increase in darunavir exposure mediated by ritonavir co administration and the decrease in darunavir exposure observed during pregnancy. PMID- 26369775 TI - The First-in-Class Potassium-Competitive Acid Blocker, Vonoprazan Fumarate: Pharmacokinetic and Pharmacodynamic Considerations. AB - Vonoprazan fumarate (Takecab) is a first-in-class potassium-competitive acid blocker that has been available in the market in Japan since February 2015. Vonoprazan is administered orally at 20 mg once daily for the treatment of gastroduodenal ulcer, at 20 and 10 mg once daily for the treatment and secondary prevention of reflux esophagitis, respectively, at 10 mg once daily for the secondary prevention of low-dose aspirin- or non-steroidal anti-inflammatory drug induced peptic ulcer, and at 20 mg twice daily in combination with clarithromycin and amoxicillin for the eradication of Helicobacter pylori. It inhibits H(+),K(+) ATPase activities in a reversible and potassium-competitive manner with a potency of inhibition approximately 350 times higher than the proton pump inhibitor, lansoprazole. Vonoprazan is absorbed rapidly and reaches maximum plasma concentration at 1.5-2.0 h after oral administration. Food has minimal effect on its intestinal absorption. Oral bioavailability in humans remains unknown. The plasma protein binding of vonoprazan is 80% in healthy subjects. It distributes extensively into tissues with a mean apparent volume of distribution of 1050 L. Being a base with pKa of 9.6 and with acid-resistant properties, vonoprazan is highly concentrated in the acidic canaliculi of the gastric parietal cells and elicited an acid suppression effect for longer than 24 h after the administration of 20 mg. The mean apparent terminal half-life of the drug is approximately 7.7 h in healthy adults. Vonoprazan is metabolized to inactive metabolites mainly by cytochrome P450 (CYP)3A4 and to some extent by CYP2B6, CYP2C19, CYP2D6, and SULT2A1. A mass balance study showed that 59 and 8% of the orally administered radioactivity was recovered in urine as metabolites and in an unchanged form, respectively, indicating extensive metabolism. Genetic polymorphism of CYP2C19 may influence drug exposure but only to a clinically insignificant extent (15 29%), according to the population pharmacokinetic study performed in Japanese patients. When vonoprazan was co-administered with clarithromycin, the mean AUC from time 0 to time of the next dose (dosing interval) of vonoprazan and clarithromycin were increased by 1.8 and 1.5 times, respectively, compared with the corresponding control values, indicating mutual metabolic inhibition. The mean area under the curve from time zero to infinity obtained from patients with severe liver and renal dysfunction were elevated by 2.6 and 2.4 times, respectively, compared with healthy subjects, with no significant changes in plasma protein binding. Vonoprazan increases intragastric pH above 4.0 as early as 4 h after an oral dose of 20 mg, and the extensive anti-secretory effect is maintained up to 24 h post-dose. During repeated dosing of 20 mg once daily, the 24-h intragastric pH >4 holding time ratios were 63 and 83 % on days 1 and 7, respectively. Because vonoprazan elicited a more extensive gastric acid suppression than the proton pump inhibitor, lansoprazole, it also gave rise to two to three times greater serum gastrin concentrations as compared with lansoprazole. In pre-approval clinical studies for the treatment of acid-related disorders, mild to moderate adverse drug reactions (mostly constipation or diarrhea) occurred at frequencies of 8-17%. Neither severe liver toxicity nor neuroendocrine tumor has been reported in patients receiving vonoprazan. PMID- 26369776 TI - Predicting the Effect of CYP3A Inducers on the Pharmacokinetics of Substrate Drugs Using Physiologically Based Pharmacokinetic (PBPK) Modeling: An Analysis of PBPK Submissions to the US FDA. AB - BACKGROUND AND OBJECTIVE: We recently published analyses regarding the predictive performance of physiologically based pharmacokinetic (PBPK) models, submitted to the US Food and Drug Administration (FDA), for the effect of cytochrome P450 (CYP) inhibitors on the pharmacokinetics of substrate drugs. We now analyze and summarize the predictive performance of PBPK models for the effect of CYP3A inducers on a substrate's pharmacokinetics. METHODS: This analysis was based on 11 substrate PBPK models, developed by six sponsors, using a commercial PBPK software, with 13 clinical interaction studies. Four CYP3A inducers were used: rifampicin, rifabutin, carbamazepine, and efavirenz. Sponsors either directly used the software-provided inducer models or verified these models' induction magnitude prior to use. The metric for assessing predictive performance was the R predicted/observed value [R predicted/observed = (predicted mean exposure ratio)/(observed mean exposure ratio)], with the exposure ratio defined as maximum plasma concentration (C max) or area under the plasma concentration-time curve (AUC) with and without an inducer. RESULTS: In 77% (10/13; AUCR) and 83% (10/12; C max R) of the cases, the R predicted/observed values were within 1.25 fold of the observed data. Cases with R predicted/observed values >1.25-fold (>twofold for all three AUCR) were under-predictions as a result of using the PBPK software's default rifampicin model. Improved predictions were observed when the rifampicin model was modified by increasing the induction potency. CONCLUSION: Based on submissions to the FDA, and similar to our previous findings for CYP inhibition, we observed good agreement between PBPK-predicted and observed effect of CYP3A inducers on substrate pharmacokinetics. Verification of the inducer model appears to be crucial for improved predictive performance. PMID- 26369774 TI - Impact of New Genomic Technologies on Understanding Adverse Drug Reactions. AB - It is well established that variations in genes can alter the pharmacokinetic and pharmacodynamic profile of a drug and immunological responses to it. Early advances in pharmacogenetics were made with traditional genetic techniques such as functional cloning of genes using knowledge gained from purified proteins, and candidate gene analysis. Over the past decade, techniques for analysing the human genome have accelerated greatly as knowledge and technological capabilities have grown. These techniques were initially focussed on understanding genetic factors of disease, but increasingly they are helping to clarify the genetic basis of variable drug responses and adverse drug reactions (ADRs). We examine genetic methods that have been applied to the understanding of ADRs, review the current state of knowledge of genetic factors that influence ADR development, and discuss how the application of genome-wide association studies and next-generation sequencing approaches is supporting and extending existing knowledge of pharmacogenetic processes leading to ADRs. Such approaches have identified single genes that are major contributing genetic risk factors for an ADR, (such as flucloxacillin and drug-induced liver disease), making pre-treatment testing a possibility. They have contributed to the identification of multiple genetic determinants of a single ADR, some involving both pharmacologic and immunological processes (such as phenytoin and severe cutaneous adverse reactions). They have indicated that rare genetic variants, often not previously reported, are likely to have more influence on the phenotype than common variants that have been traditionally tested for. The problem of genotype/phenotype discordance affecting the interpretation of pharmacogenetic screening and the future of genome-based testing applied to ADRs are also discussed. PMID- 26369777 TI - In-Depth Characterization of Protein Disulfide Bonds by Online Liquid Chromatography-Electrochemistry-Mass Spectrometry. AB - Disulfide bonds are an important class of protein post-translational modifications, yet this structurally crucial modification type is commonly overlooked in mass spectrometry (MS)-based proteomics approaches. Recently, the benefits of online electrochemistry-assisted reduction of protein S-S bonds prior to MS analysis were exemplified by successful characterization of disulfide bonds in peptides and small proteins. In the current study, we have combined liquid chromatography (LC) with electrochemistry (EC) and mass analysis by Fourier transform ion cyclotron resonance (FTICR) MS in an online LC-EC-MS platform to characterize protein disulfide bonds in a bottom-up proteomics workflow. A key advantage of a LC-based strategy is the use of the retention time in identifying both intra- and interpeptide disulfide bonds. This is demonstrated by performing two sequential analyses of a certain protein digest, once without and once with electrochemical reduction. In this way, the "parent" disulfide-linked peptide detected in the first run has a retention time-based correlation with the EC reduced peptides detected in the second run, thus simplifying disulfide bond mapping. Using this platform, both inter- and intra-disulfide-linked peptides were characterized in two different proteins, beta-lactoglobulin and ribonuclease B. In order to prevent disulfide reshuffling during the digestion process, proteins were digested at a relatively low pH, using (a combination of) the high specificity proteases trypsin and Glu-C. With this approach, disulfide bonds in beta-lactoglobulin and ribonuclease B were comprehensively identified and localized, showing that online LC-EC-MS is a useful tool for the characterization of protein disulfide bonds. PMID- 26369778 TI - Protein Structural Studies by Traveling Wave Ion Mobility Spectrometry: A Critical Look at Electrospray Sources and Calibration Issues. AB - The question whether electrosprayed protein ions retain solution-like conformations continues to be a matter of debate. One way to address this issue involves comparisons of collision cross sections (Omega) measured by ion mobility spectrometry (IMS) with Omega values calculated for candidate structures. Many investigations in this area employ traveling wave IMS (TWIMS). It is often implied that nanoESI is more conducive for the retention of solution structure than regular ESI. Focusing on ubiquitin, cytochrome c, myoglobin, and hemoglobin, we demonstrate that Omega values and collisional unfolding profiles are virtually indistinguishable under both conditions. These findings suggest that gas-phase structures and ion internal energies are independent of the type of electrospray source. We also note that TWIMS calibration can be challenging because differences in the extent of collisional activation relative to drift tube reference data may lead to ambiguous peak assignments. It is demonstrated that this problem can be circumvented by employing collisionally heated calibrant ions. Overall, our data are consistent with the view that exposure of native proteins to electrospray conditions can generate kinetically trapped ions that retain solution-like structures on the millisecond time scale of TWIMS experiments. ? PMID- 26369779 TI - Down-regulation of plant defence in a resident spider mite species and its effect upon con- and heterospecifics. AB - Herbivorous spider mites occurring on tomato plants (Solanum lycopersicum L.) cope with plant defences in various manners: the invasive Tetranychus evansi reduces defences below constitutive levels, whereas several strains of T. urticae induce such defences and others suppress them. In the Mediterranean region, these two species co-occur on tomato plants with T. ludeni, another closely related spider mite species. Unravelling how this third mite species affects plant defences is thus fundamental to understanding the outcome of herbivore interactions in this system. To test the effect of T. ludeni on tomato plant defences, we measured (1) the activity of proteinase inhibitors, indicating the induction of plant defences, in those plants, and (2) mite performance on plants previously infested with each mite species. We show that the performance of T. evansi and T. ludeni on plants previously infested with T. ludeni or T. evansi was better than on clean plants, indicating that these two mite species down regulate plant defences. We also show that plants attacked by these mite species had lower activity of proteinase inhibitors than clean plants, whereas herbivory by T. urticae increased the activity of these proteins and resulted in reduced spider mite performance. This study thus shows that the property of down regulation of plant defences below constitutive levels also occurs in T. ludeni. PMID- 26369780 TI - Juvenile river herring habitat use and marine emigration trends: comparing populations. AB - Juvenile habitat use and early life migratory behaviors of successfully recruited adult fish provide unique insight into critical habitats for a population, and this information allows restoration plans to be tailored to maximize benefits. Retrospective analysis of adult otolith chemistry combined with fish-otolith growth models were used to assess juvenile nursery habitat selection and size at egress to adult habitats (marine waters) for anadromous alewife and blueback herring from 20 rivers throughout the eastern US. Between-species differences in the size of emigrants were small, with blueback herring found in freshwater nurseries ~ 8% more frequently than alewives, and alewives using a combination of freshwater and estuarine nurseries ~ 9% more than bluebacks. Estuarine nursery use was more common in populations at lower latitudes. No clear trends in sizes of emigrants or habitat use were observed between the species in watersheds where both co-occur. Principal component analysis of latitude, watershed area, estuary area, accessible river kilometers, and percentage of the watershed in urban use indicated that the combined effects of these watershed characteristics were correlated with size at egress. These results highlight the considerable plasticity in early life habitat use among populations of anadromous fishes as well as the effect of watershed characteristics on early life migration timing and strategies. PMID- 26369781 TI - Medicinal plants used to treat the most frequent diseases encountered in Ambalabe rural community, Eastern Madagascar. AB - BACKGROUND: Traditional medicine remains the only health care available in many rural areas in Madagascar like the rural community of Ambalabe, located in a very remote area in the eastern part of the country. With limited access to modern medicine, the local population uses medicinal plants to treat most diseases. In this study, we aimed to inventory medicinal plants used by local people and how those relate to the treatment of the most frequent diseases encountered in Ambalabe. METHODS: We interviewed participants in order to identify the most frequent diseases in the region and the medicinal plants used to treat them. The local physician was asked about the most frequent diseases, and ethnobotanical surveys to record medicinal plants and their uses, using semi-structured interviews and free listing, were conducted among 193 informants in local villages, of which 54 % were men and 46 % were women, ageing from 16 to 86 years. The local names, the uses of each plant species and the way they are prepared and administered were recorded and accompanied by herbarium specimens for identification. We also interviewed four traditional healers to elicit more details on the preparation and the use of plants. RESULTS: Our research allowed us to identify six most frequent diseases, namely diarrhea, malaria, stomach ache, cough, bilharzia and dysentery. Among 209 plant species identified as having medicinal use, 83 species belonging to 49 families and 77 genera were used to treat these diseases. Our analyses highlighted the 11 commonly used species for their treatment, and also 16 species with a high fidelity level (FL >= 75 %) for each ailment. Diarrhea is one of the diseases with high number of species recorded. CONCLUSIONS: This study highlighted the closed relationship between people in Ambalabe and plant species, especially when faced with frequent diseases. However, most of the species used were collected in the surroundings of the villages. Few species were from Vohibe forest in which a management system on the use of plant species was already established. Therefore, a sustainable use management should be considered for wild species from which medicinal plants are highly abundant. PMID- 26369782 TI - Comparative Proteome of Acetobacter pasteurianus Ab3 During the High Acidity Rice Vinegar Fermentation. AB - As a traditional Asian food for several centuries, vinegar is known to be produced by acetic acid bacteria. The Acetobacter species is the primary starter for vinegar fermentation and has evolutionarily acquired acetic acid resistance, in which Acetobacter pasteurianus Ab3 is routinely used for industrial production of rice vinegar with a high acidity (9 %, w/v). In contrast to the documented short-term and low acetic acid effects on A. pasteurianus, here we investigated the molecular and cellular signatures of long-term and high acetic acid responses by proteomic profiling with bidimensional gel electrophoresis and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI TOF/MS) analyses. Protein spots of interest were selected based on the threshold ANOVA p value of 0.05 and minimal twofold of differential expression, leading to the identification of 26 proteins that are functionally enriched in oxidoreductase activity, cell membrane, and metabolism. The alterations in protein functioning in respiratory chain and protein denaturation may underlay cellular modifications at the outer membrane. Significantly, we found that at higher acidity fermentation phase, the A. pasteurianus Ab3 cells would adapt to distinct physiological processes from that of an ordinary vinegar fermentation with intermediate acidity, indicating increasing energy requirement and dependency of membrane integrity during the transition of acetic acid production. Together, our study provided new insights into the adaptation mechanisms in A. pasteurianus to high acetic acid environments and yield novel regulators and key pathways during the development of acetic acid resistance. PMID- 26369783 TI - A New Hydrogen-Producing Strain and Its Characterization of Hydrogen Production. AB - A newly isolated photo non-sulfur (PNS) bacterium was identified as Rhodopseudomonas palustris PB-Z by sequencing of 16S ribosomal DNA (rDNA) genes and phylogenetic analysis. Under vigorous stirring (240 rpm), the hydrogen production performances were greatly improved: The maximum hydrogen production rate and cumulative hydrogen production increased by 188.9 +/- 0.07 % and 83.0 +/ 0.06 %, respectively, due to the hydrogen bubbles were immediately removed from the culture medium. The effects of different wavelength of light on hydrogen production with stirring were much different from that without stirring. The ranking on the photo-hydrogen production performance was white > yellow > green > blue > red without stirring and white > yellow > blue > red > green under stirring. The best light source for hydrogen production was tungsten filament lamp. The optimum temperature was 35 degrees C. The maximal hydrogen production rate and cumulative hydrogen production reached 78.7 +/- 2.3 ml/l/h and 1728.1 +/ 92.7 mol H2/l culture, respectively, under 35 degrees C, 240 rpm, and illumination of 4000 lux. Pyruvate was one of the main sources of CO2 and has a great impact on the gas composition. PMID- 26369784 TI - Clinical classification of tissue perfusion based on the central venous oxygen saturation and the peripheral perfusion index. AB - INTRODUCTION: We investigated whether combining the peripheral perfusion index (PI) and central venous oxygen saturation(ScvO2) would identify subsets of patients for assessing the tissue perfusion and predicting outcome during the resuscitation in critically ill patients. METHODS: A total of 202 patients with central venous catheters for resuscitation were enrolled in this prospective observational study. The arterial, central venous blood gas and the PI were measured simultaneously at the enrollment (T0) and 8 h (T8) after early resuscitation. Based on the distribution of the PI in healthy population, a cutoff of PI >= 1.4 was defined as a normal PI. Moreover, the critical value of PI was defined as the best cutoff value related to the mortality in the study population. The PI impairment stratification is defined as follows: a normal PI(>= 1.4), mild PI impairment (critical value < PI < 1.4) and critical PI impairment (PI <= critical value). RESULTS: The PI at T8 was with the greatest AUC for prediction the 30-day mortality and PI is an independent risk factor for 30-day mortality. Moreover, a cutoff of PI < 0.6 is related to poor outcomes following resuscitation. So, based on cutoffs of ScvO2 (70%) and critical PI (0.6) at T8, we assigned the patients to four categories: group 1 (PI <= 0.6 on ScvO2 < 70%), group 2 (PI <= 0.6 on ScvO2 >= 70%), group 3 (PI > 0.6 on ScvO2 < 70%), and group 4 (PI > 0.6 on ScvO2 >= 70%). The combination of low ScvO2(<70%) and PI(<= 0.6) was associated with the lowest survival rates at 30 days [log rank (Mantel-Cox) = 87.518, p < 0.0001]. The sub-group patients who had high ScvO2(>80%) at T8 were with low mortality and high PI. Moreover, the normal PI (>= 1.4) did not show a better outcome than mild impaired PI (0.6-1.4) patients who had a normalized ScvO2(>70%) after resuscitation. The PI was correlated with the lactate, P(v-a)CO2, and ScvO2 in all the measurements (n = 404). These relationships are strengthened with abnormal PI (PI < 1.4) but not with normal PI (PI >= 1.4). CONCLUSION: Complementing ScvO2 assessment with PI can better identify endpoints of resuscitation and adverse outcomes. Pursuing a normalized PI (>= 1.4) may not result in better outcomes for a mild impaired PI after ScvO2 is normalized. PMID- 26369785 TI - Executive functions among youth with Down Syndrome and co-existing neurobehavioural disorders. AB - BACKGROUND: Executive function (EF) deficits are a recognised component of the cognitive phenotype of youth with Down Syndrome (DS). Recent research in this area emphasises the use of behaviour ratings, such as the Behavior Rating Inventory of Executive Functions-Preschool Version (BRIEF-P), to capture the real world applications of executive functions. To account for the intellectual functioning of youth with DS, this measure is used out of age range; however, its psychometric properties when used in this fashion are unknown. The goals of this study are to evaluate psychometric characteristics of the BRIEF-P among youth with DS and to examine the pattern of EF strengths/weaknesses in children with DS and co-occurring psychiatric conditions. METHOD: A total of 188 clinically referred youth with DS, ages 3-13 were rated by their caregivers using the BRIEF P. These youth were evaluated by a clinician with expertise in DS and were characterised as having no co-occurring behavioural disorder (Typical DS group), co-occurring Autism Spectrum Disorder (DS + ASD) or co-occurring Disruptive Behaviour Disorder (DS + DBD). RESULTS: An exploratory factor analysis of item level BRIEF-P data from clinically referred youth with DS supported the theoretically derived three-factor structure originally proposed for the BRIEF-P (Emergent Metacognition, Flexibility and Inhibitory Self-Control); however, the item composition of each factor varied somewhat in comparison to the original structure of the measure. Group comparisons indicate that, while youth with typical DS evidence fewer executive function difficulties across all domains, youth with DS + ASD show the greatest weaknesses in Emergent Metacognition, and youth with DS + DBD show significant difficulties in both Emergent Metacognition and Inhibition. CONCLUSIONS: These findings offer preliminary support for use of the BRIEF-P with clinically referred youth with Down Syndrome. Some scoring modifications may be necessary if the theoretically derived index scores are to be used with this population. BRIEF-P scores may offer an empirical basis for differentiating DS youth with varying behavioural profiles. PMID- 26369786 TI - Tandem Mass Spectrometry Has a Larger Analytical Range than Fluorescence Assays of Lysosomal Enzymes: Application to Newborn Screening and Diagnosis of Mucopolysaccharidoses Types II, IVA, and VI. AB - BACKGROUND: There is interest in newborn screening and diagnosis of lysosomal storage diseases because of the development of treatment options that improve clinical outcome. Assays of lysosomal enzymes with high analytical range (ratio of assay response from the enzymatic reaction divided by the assay response due to nonenzymatic processes) are desirable because they are predicted to lead to a lower rate of false positives in population screening and to more accurate diagnoses. METHODS: We designed new tandem mass spectrometry (MS/MS) assays that give the largest analytical ranges reported to date for the use of dried blood spots (DBS) for detection of mucopolysaccharidoses type II (MPS-II), MPS-IVA, and MPS-VI. For comparison, we carried out fluorometric assays of 6 lysosomal enzymes using 4-methylumbelliferyl (4MU)-substrate conjugates. RESULTS: The MS/MS assays for MPS-II, -IVA, and -VI displayed analytical ranges that are 1-2 orders of magnitude higher than those for the corresponding fluorometric assays. The relatively small analytical ranges of the 4MU assays are due to the intrinsic fluorescence of the 4MU substrates, which cause high background in the assay response. CONCLUSIONS: These highly reproducible MS/MS assays for MPS-II, -IVA, and -VI can support multiplex newborn screening of these lysosomal storage diseases. MS/MS assays of lysosomal enzymes outperform 4MU fluorometric assays in terms of analytical range. Ongoing pilot studies will allow us to gauge the impact of the increased analytical range on newborn screening performance. PMID- 26369787 TI - Rapid, Fully Automated Digital Immunoassay for p24 Protein with the Sensitivity of Nucleic Acid Amplification for Detecting Acute HIV Infection. AB - BACKGROUND: Nucleic acid testing (NAT) has become the standard for high sensitivity in detecting low levels of virus. However, adoption of NAT can be cost prohibitive in low-resource settings where access to extreme sensitivity could be clinically advantageous for early detection of infection. We report development and preliminary validation of a simple, low-cost, fully automated digital p24 antigen immunoassay with the sensitivity of quantitative NAT viral load (NAT-VL) methods for detection of acute HIV infection. METHODS: We developed an investigational 69-min immunoassay for p24 capsid protein for use on a novel digital analyzer on the basis of single-molecule-array technology. We evaluated the assay for sensitivity by dilution of standardized preparations of p24, cultured HIV, and preseroconversion samples. We characterized analytical performance and concordance with 2 NAT-VL methods and 2 contemporary p24 Ag/Ab combination immunoassays with dilutions of viral isolates and samples from the earliest stages of HIV infection. RESULTS: Analytical sensitivity was 0.0025 ng/L p24, equivalent to 60 HIV RNA copies/mL. The limit of quantification was 0.0076 ng/L, and imprecision across 10 runs was <10% for samples as low as 0.09 ng/L. Clinical specificity was 95.1%. Sensitivity concordance vs NAT-VL on dilutions of preseroconversion samples and Group M viral isolates was 100%. CONCLUSIONS: The digital immunoassay exhibited >4000-fold greater sensitivity than contemporary immunoassays for p24 and sensitivity equivalent to that of NAT methods for early detection of HIV. The data indicate that NAT-level sensitivity for acute HIV infection is possible with a simple, low-cost digital immunoassay. PMID- 26369788 TI - Barriers to diabetic foot care in a developing country with a high incidence of diabetes related amputations: an exploratory qualitative interview study. AB - BACKGROUND: Diabetes related foot disease is a major cause of morbidity and mortality in people with diabetes. This is despite the fact that interventions to reduce the burden of diabetic foot disease are estimated to be highly cost effective, even cost saving in both developed and developing countries. This exploratory qualitative study was undertaken in a developing country known to have a very high rate of diabetes related amputations. The aim of the study was to explore barriers to foot care from the perspectives of health care professionals and patients, with a view to informing further work to develop effective interventions. METHODS: Semi-structured interviews, each of 30 to 60 minutes, were conducted with a purposive sample of 20 individuals (11 health carers and 9 patients with diabetes). Participants were asked how diabetic foot care was experienced and practised, and about knowledge and attitudes relevant to care. Health carers were also asked how they negotiated issues of priority setting within the available resources. Interviews were recorded, transcribed and underwent thematic analysis. RESULTS: Three broad categories of potential barriers to diabetic foot care were identified. First, health carers reported that they and their patients tended to prioritise glycaemic control and that this often eclipsed foot care. Second, health carers described resistance to changing professional roles, particularly within the context of limited resources. Newly assigned foot screening and care duties did not fit in easily with their main work schedule. The overall effect of this was to lead to increased referrals to already overstretched, and difficult to access, podiatrists. Finally, patients reported a health care system with significant reliance on 'self-care' ability, including the need for time and expertise to negotiate access to scarce professional foot care appointments. CONCLUSIONS: The findings from this exploratory study provide insight on broad barriers to diabetic foot care within a developing country setting. The three areas identified deserve further investigation to determine their impact on the delivery of diabetic foot care and the implications for designing effective interventions. PMID- 26369789 TI - Genetic characterization of Bagarius species using cytochrome c oxidase I and cytochrome b genes. AB - In this study, we first inferred the genetic variability of two Bagarius bagarius populations collected from Ganges and Brahmaputra rivers of India using two mtDNA markers. Sequence analysis of COI gene did not show significant differences between two populations whereas cytochrome b gene showed significant differences between two populations. Followed by, genetic relationship of B. bagarius and B. yarrielli was analyzed using COI and cytochrome b gene and the results showed a higher level genetic variation between two species. The present study provides support for the suitability of COI and cytochrome b genes for the identification of B. bagarius and B. yarrielli. PMID- 26369790 TI - Pasteurella multocida toxin- induced osteoclastogenesis requires mTOR activation. AB - BACKGROUND: Pasteurella multocida toxin (PMT) is a potent inducer of osteoclast formation. Pigs suffering from an infection with toxigenic Pasteurella multocida strains develop atrophic rhinitis characterised by a loss of turbinate bones and conchae. However, on the molecular level the process of bone loss remains largely uncharacterised. RESULTS: Recently it was found that PMT activates the serine/threonine kinase mammalian target of rapamycin (mTOR) in fibroblasts. Using RAW264.7 macrophages, we investigated the role of the mTOR complex 1 (mTORC1) in PMT-mediated osteoclast formation. PMT induces the differentiation of RAW264.7 macrophages into multinucleated, tartrate resistant acid phosphatase (TRAP) positive osteoclasts that are capable to resorb bone. In the presence of the mTORC1 inhibitor rapamycin, PMT was significantly less able to induce the formation of TRAP-positive osteoclasts. Accordingly, the resulting resorption of bone was strongly reduced. A major target of mTOR is the 70 kDa ribosomal protein S6 kinase 1 (p70 S6K1). Activated p70 S6K1 decreases the expression of programmed cell death protein 4 (PDCD4), a negative transcriptional regulator of osteoclastogenesis, at the protein and gene level. Ultimately this results in the activation of c-Jun, a component of the activator protein 1 (AP-1) complex, which is a major transcription factor for the induction of osteoclast-specific genes. We now demonstrate that c-Jun and its downstream target, the osteoclast-specific bone degrading protease cathepsin K, are upregulated upon PMT treatment in an mTOR-dependent manner. CONCLUSIONS: Activation of mTOR signalling plays a central role in the formation of osteoclasts through the bacterial toxin PMT. On the molecular level, PMT-induced activation of mTOR leads to down regulation of PDCD4, a known repressor of AP-1 complex, culminating in the activation of c-Jun, an essential transcription factor for triggering osteoclastogenesis. PMID- 26369791 TI - Transcriptome analysis of complex I-deficient patients reveals distinct expression programs for subunits and assembly factors of the oxidative phosphorylation system. AB - BACKGROUND: Transcriptional control of mitochondrial metabolism is essential for cellular function. A better understanding of this process will aid the elucidation of mitochondrial disorders, in particular of the many genetically unsolved cases of oxidative phosphorylation (OXPHOS) deficiency. Yet, to date only few studies have investigated nuclear gene regulation in the context of OXPHOS deficiency. In this study we performed RNA sequencing of two control and two complex I-deficient patient cell lines cultured in the presence of compounds that perturb mitochondrial metabolism: chloramphenicol, AICAR, or resveratrol. We combined this with a comprehensive analysis of mitochondrial and nuclear gene expression patterns, co-expression calculations and transcription factor binding sites. RESULTS: Our analyses show that subsets of mitochondrial OXPHOS genes respond opposingly to chloramphenicol and AICAR, whereas the response of nuclear OXPHOS genes is less consistent between cell lines and treatments. Across all samples nuclear OXPHOS genes have a significantly higher co-expression with each other than with other genes, including those encoding mitochondrial proteins. We found no evidence for complex-specific mRNA expression regulation: subunits of different OXPHOS complexes are similarly (co-)expressed and regulated by a common set of transcription factors. However, we did observe significant differences between the expression of nuclear genes for OXPHOS subunits versus assembly factors, suggesting divergent transcription programs. Furthermore, complex I co expression calculations identified 684 genes with a likely role in OXPHOS biogenesis and function. Analysis of evolutionarily conserved transcription factor binding sites in the promoters of these genes revealed almost all known OXPHOS regulators (including GABP, NRF1/2, SP1, YY1, E-box factors) and a set of novel candidates (ELK1, KLF7, SP4, EHF, ZNF143, and TEL2). CONCLUSIONS: OXPHOS genes share an expression program distinct from other genes encoding mitochondrial proteins, indicative of targeted nuclear regulation of a mitochondrial sub-process. Within the subset of OXPHOS genes we established a difference in expression between mitochondrial and nuclear genes, and between nuclear genes encoding subunits and assembly factors. Most transcription regulators of genes that co-express with complex I are well-established factors for OXPHOS biogenesis. For the remaining six factors we here suggest for the first time a link with transcription regulation in OXPHOS deficiency. PMID- 26369792 TI - Specific detection of foot-and-mouth disease serotype Asia 1 virus by carboxyl magnetic beads conjugated with single-domain antibody. AB - BACKGROUND: Immunomagnetic nanobead (IMNB) labeled with specific antibody, has been demonstrated to be useful for the capturing and detection of viruses. RESULTS: In this study, we developed an imunomagnetic bead based on carboxyl magnetic beads (MNB) labeled with a single-domain antibody (sdAb) for capturing foot-and-mouth disease (FMD) Asia 1 virus. After magnetic separation, complexes of MNB-sdAb-virus were detected with either a sandwich ELISA or QDs-C5 probe under a fluorescence microscope, and the complexes were used as templates for extraction of total RNA for amplification of the VP1 or 3D gene fragments using RT-PCR and real-time RT-PCR. The Asia 1 VLPs were efficiently captured through IMNB with a high binding rate of 5.09 MUg of antigen/MUl of bead suspension. Moreover, this method has been successfully used to capture Asia 1 antigen in synthetic samples. CONCLUSION: Ultimately, a specific and highly sensitive capture FMDV Asia 1 tool has been established that has the potential to enhance the sensitivity and reliability when diagnosing FMDV Asia 1. PMID- 26369793 TI - In silico mutational studies of Hsp70 disclose sites with distinct functional attributes. AB - The Mutation-Minimization Method (MuMi) to study the local response of proteins to point mutations has been introduced here. The heat shock protein Hsp70 as the test system since it displays features that have been studied in great detail has been used here. It has many conserved residues, serves several different functions on each of its domains, and displays interdomain allostery. For the analysis of spatial arrangement of residues within the protein, the network properties of the wild type (WT) protein as well as its all single alanine residue mutants using MuMi has been investigated. The measures to express the amount of change from the WT structure upon mutation and compare these deviations to find potential critical sites have been proposed. The functional significance of the potential sites to the parameter that uncovers them has been mapped. It was found that sites directly involved in binding were sensitive to mutations and were characterized by large displacements. On the other hand, sites that steer large conformational changes typically had increased reachability upon alanine mutations occurring elsewhere in the protein. Finally, residues that control communication within and between domains reside on the largest number of paths connecting pairs of residues in the protein. PMID- 26369794 TI - Robotic-assisted laparoscopic prostatectomy: An update on functional and oncologic outcomes, techniques, and advancements in technology. AB - The robotic platform has revolutionized the management of prostate cancer over the last 15 years. Several techniques have been developed to improve functional and oncologic outcomes, including meticulous apical and posterior dissection, nerve sparing techniques, bladder neck and urethral length sparing, and anastomotic reconstruction. Future developments involving novel single-site, robotic technology will undoubtedly further the field of minimally invasive urology. These topics are reviewed within this article. PMID- 26369795 TI - 'It doesn't do the care for you': a qualitative study of health care professionals' perceptions of the benefits and harms of integrated care pathways for end of life care. AB - OBJECTIVES: To understand healthcare professionals' perceptions of the benefits and potential harms of integrated care pathways for end-of-life care, to inform the development of future interventions that aim to improve care of the dying. DESIGN: Qualitative interview study with maximum variation sampling and thematic analysis. PARTICIPANTS: 25 healthcare professionals, including doctors, nurses and allied health professionals, interviewed in 2009. SETTING: A 950-bed South London teaching hospital. RESULTS: 4 main themes emerged, each including 2 subthemes. Participants were divided between (1) those who described mainly the benefits of integrated care pathways, and (2) those who talked about potential harms. Benefits focused on processes of care, for example, clearer, consistent and comprehensive actions. The recipients of these benefits were staff members themselves, particularly juniors. For others, this perceived clarity was interpreted as of potential harm to patients, where over-reliance on paperwork lead to prescriptive, less thoughtful care, and an absolution from decision making. Independent of their effects on patient care, integrated care pathways for dying had (3) a symbolic value: they legitimised death as a potential outcome and were used as a signal that the focus of care had changed. However, (4) a weak infrastructure, including scanty education and training in end-of-life care and a poor evidence base, that appeared to undermine the foundations on which the Liverpool Care Pathway was built. CONCLUSIONS: The potential harms of integrated care pathways for the dying identified in this study were reminiscent of criticisms subsequently published by the Neuberger review. These data highlight: (1) the importance of collecting, reporting and using qualitative data when developing and evaluating complex interventions; (2) that comprehensive education and training in palliative care is critical for the success of any new intervention; (3) the need for future interventions to be grounded in patient centred outcomes, not just processes of care. PMID- 26369796 TI - Mapping patients' experiences from initial symptoms to gout diagnosis: a qualitative exploration. AB - OBJECTIVE: To explore patients' experiences from initial symptoms to receiving a diagnosis of gout. DESIGN: Data from in-depth semistructured interviews were used to construct themes to describe key features of patients' experiences of gout diagnosis. PARTICIPANTS AND SETTING: A maximum variation sample of 43 UK patients with gout (29 men; 14 women; age range 32-87 years) were recruited from general practices, rheumatology clinics, gout support groups and through online advertising. RESULTS: Severe joint pain, combined with no obvious signs of physical trauma or knowledge of injury, caused confusion for patients attempting to interpret their symptoms. Reasons for delayed consultation included self diagnosis and/or self-medication, reluctance to seek medical attention, and financial/work pressures. Factors potentially contributing to delayed diagnosis after consultation included reported misdiagnosis, attacks in joints other than the first metatarsophalangeal joint, and female gender. The limitations in using serum uric acid (SUA) levels for diagnostic purposes were not always communicated effectively to patients, and led to uncertainty and lack of confidence in the accuracy of the diagnosis. Resistance to the diagnosis occurred in response to patients' beliefs about the causes of gout and characteristics of the people likely to be affected. Diagnosis prompted actions, such as changes in diet, and evidence was found of self-monitoring of SUA levels. CONCLUSIONS: This study is the first to report data specifically about patients' pathways to initial consultation and subsequent experiences of gout diagnosis. A more targeted approach to information provision at diagnosis would improve patients' experiences. PMID- 26369797 TI - Does the Finnish intervention prevent obstetric anal sphincter injuries? A systematic review of the literature. AB - OBJECTIVES: A rise in obstetric anal sphincter injuries (OASIS) has been observed and a preventive approach, originating in Finland, has been introduced in several European hospitals. The aim of this paper was to systematically evaluate the evidence behind the 'Finnish intervention'. DESIGN: A systematic review of the literature conducted according to the Preferred Reporting for Systematic Reviews and Meta-analyses (PRISMA) guidelines. OUTCOME MEASURES: The primary outcome was OASIS. Secondary outcomes were (perinatal): Apgar scores, pH and standard base excess in the umbilical cord, and (maternal): episiotomy, intact perineum, first and second-degree perineal lacerations, duration of second stage, birth position and women's perceptions/birth experiences. METHODS: Multiple databases (Cochrane, Embase, Pubmed and SveMed) were systematically searched for studies published up to December 2014. Both randomised controlled trials and observational studies were eligible for inclusion. Studies were excluded if a full-text article was not available. Studies were evaluated by use of international reporting guidelines (eg, STROBE). RESULTS: Overall, 1042 articles were screened and 65 retrieved for full-text evaluation. Seven studies, all observational and with a level of evidence at 2c or lower, were included and consistently reported a significant reduction in OASIS. All evaluated episiotomy and found a significant increase. Three studies evaluated perinatal outcomes and reported conflicting results. No study reported on other perineal outcomes, duration of the second stage, birth positions or women's perceptions. CONCLUSIONS: A reduction in OASIS has been contributed to the Finnish intervention in seven observational studies, all with a low level of evidence. Knowledge about the potential perinatal and maternal side effects and women's perceptions of the intervention is extremely limited and the biological mechanisms underlying the Finnish intervention are not well documented. Studies with a high level of evidence are needed to assess the effects of the intervention before implementation in clinical settings can be recommended. PMID- 26369798 TI - Clinical efficacy and mechanistic evaluation of aflibercept for proliferative diabetic retinopathy (acronym CLARITY): a multicentre phase IIb randomised active controlled clinical trial. AB - INTRODUCTION: Proliferative diabetic retinopathy (PDR) is the main cause of severe visual loss in people with diabetes mellitus. The standard treatment for this condition is panretinal photocoagulation (PRP). This laser treatment is inherently destructive, with predictable adverse effects on visual function, and a safer alternative is required. Intravitreal injection of vascular endothelial growth factor (VEGF) inhibitors can induce short-term regression of retinal neovascularisation. The aim of this randomised controlled trial is to determine the efficacy, safety and cost-effectiveness of intravitreal aflibercept, an inhibitor of VEGF-A, VEGF-B and placental growth factor (PLGF), in PDR, and to investigate the impact on local oxygenation. METHODS AND ANALYSIS: This is a phase IIb randomised controlled single-masked multicentre clinical trial to determine the impact of repeated intravitreal aflibercept injections in the treatment and prevention of PDR. 220 participants with treatment-naive or treated but active retinal neovascularisation in at least one eye will be randomly allocated 1:1 to intravitreal aflibercept injections or PRP for a period of 52 weeks. The primary outcome is the change in best-corrected visual acuity in the study eye at 52 weeks. Secondary outcomes include changes from baseline in other visual functions, anatomical changes and cost-effectiveness. Ocular and non ocular adverse events will also be reported over 52 weeks. ETHICS AND DISSEMINATION: The study has been approved by the National Research Ethics Service (NRES) committee with respect to scientific content and compliance with applicable research and human subjects' regulations. Findings will be reported through scientific publications and research conferences. The results of this study will provide clinical evidence for the feasibility, efficacy safety and cost-effectiveness of intravitreal aflibercept for PDR. TRIAL REGISTRATION NUMBER: ISRCTN 32207582. PMID- 26369799 TI - Comparing socially disadvantaged smokers who agree and decline to participate in a randomised smoking cessation trial. AB - OBJECTIVES: This study examined sociodemographic, smoking and psychosocial characteristics associated with consent to participate in a smoking cessation trial for socially disadvantaged smokers. DESIGN: Baseline data were collected prior to seeking consent for the Call it Quits, a randomised controlled trial. SETTING: An Australian social and community service organisation. Sociodemographic, smoking and psychosocial characteristics were compared between smokers who agreed or declined to participate. PARTICIPANTS: Of the 584 smokers invited to participate, 431 (74%) consented and 153 (26%) declined. RESULTS: Logistic regression modelling indicates the ORs of participation were twice as high for those reporting 'high' motivation to quit compared to the 'moderate' motivation group, and five times higher than the 'low' motivation group (p=0.007). The ORs of consenting were higher for those with a preference for gradual reduction in cigarettes in quit attempts compared with 'no preference'. The ORs were lower for those reporting 'don't know' regarding their enjoyment of smoking compared to 'not at all' enjoying smoking, and reporting that fewer of their family or friends smoked compared to 'most or all'. CONCLUSIONS: This study is the first to examine the characteristics of socially disadvantaged smokers who consent or decline to participate in a smoking cessation trial. Low-income smokers who are motivated to quit, are not enjoying smoking, had family or friends who smoked, and who are interested in gradual cessation approaches may be more likely to participate in a smoking cessation trial. TRIAL REGISTRATION NUMBER: ISRCTN85202510. PMID- 26369800 TI - How do general practitioners manage patients with cancer symptoms? A video vignette study. AB - OBJECTIVES: Determine how general practitioners (GPs) manage patients with cancer symptoms. DESIGN: GPs reviewed 24 video-vignettes and case notes on patients with cancer symptoms and indicated whether they would refer the patient and/or prescribe medication, and/or undertake further investigation. According to available guidelines, all cases warranted a referral to a specialist or further investigations. SETTING: Australian primary care sector. PARTICIPANTS: 102 practising GPs participated in this study, including trainees. INTERVENTIONS: The research was part of a larger randomised controlled trial testing a referral pro forma; however, this paper reports on management decisions made throughout the study. PRIMARY AND SECONDARY OUTCOME MEASURES: This paper reports on how the participants would manage the patients depicted in each vignette. RESULTS: In more than one-in-eight cases, the patient was not investigated or referred. Patient management varied significantly by cancer type (p<0.001). For two key reasons, colorectal cancer was the chosen referent category. First, it represents a prevalent type of cancer. Second, in this study, colorectal cancer symptoms were managed in a similar proportion of options-that is, prescription, referral or investigation. Compared with vignettes featuring colorectal cancer participants were less likely to manage breast, bladder, endometrial, and lung cancers with a 'prescription only' or 'referral only' option. They were less likely to manage prostate cancer with a 'prescription only', yet more likely to manage it with a 'referral with investigation'. With regard to pancreatic and cervical cancers, participants were more likely to manage these with a 'referral only' or a 'referral with investigation'. CONCLUSIONS: Some patients may receive a delayed cancer diagnosis, even when they present with typical cancer symptoms to a GP who can access relevant diagnostic tests. TRIAL REGISTRATION NUMBER: ACTRN12611000760976. PMID- 26369801 TI - A distribution model of the responses to each depressive symptom item in a general population: a cross-sectional study. AB - OBJECTIVE: Some researchers have reported that distribution of total depressive symptom scores in the general population may follow an exponential pattern except at the lowest end of the scores. To understand the mechanism responsible for this phenomenon, we investigated the mathematical patterns of the individual distributions for each item of a depressive symptom scale. METHODS: We analysed data from 32,022 participants in the general population who participated in the Active Survey of Health and Welfare, Japan. Depressive symptoms were assessed using the Japanese version of Center for Epidemiologic Studies Depression Scale (CES-D). CES-D has 20 items, each of which is scored in 4 grades: 'Rarely', 'Some', 'Much' and 'Most of the time'. RESULTS: The individual distributions of 16 negative items belonging to the depressive mood, somatic symptoms and retarded activities, and interpersonal relations categories, followed a common mathematical pattern, which displayed different distributions with a boundary at 'Some'. The distributions for the 16 items between 'Rarely' and 'Some' appeared to cross at a single point. On the other hand, the distributions of the 16 items between 'Some' and 'Most' followed a linear pattern when plotted using a log normal scale. The remaining 4 items in the positive affect subscale showed non specific patterns. CONCLUSIONS: The common mathematical pattern of the 16 negative item distributions may contribute to the exponential pattern of the distribution of total depressive symptom scores except at the lowest end of the scores. PMID- 26369802 TI - Serum aminotransferase ratio is independently correlated with hepatosteatosis in patients with HCV: a cross-sectional observational study. AB - OBJECTIVES: The incidence of non-alcoholic fatty liver disease (NAFLD) is significant in hepatitis C virus (HCV) carriers due to multiple mechanisms, and this worsens the progression of chronic liver diseases, such as cirrhosis and hepatocellular carcinoma, and death. The purpose of this study was to examine whether the alanine aminotransferase/aspartate aminotransferase (ALT/AST) ratio correlates with the status of hepatosteatosis. DESIGN: A cross-sectional observational study. SETTING: Community-based annual examination in northern Taiwan. PARTICIPANTS: A total of 1354 participants (age 20 years or over) were enrolled after excluding participants with HCV seronegative, laboratory or questionnaires loss, moderate alcohol consumption, liver cirrhosis, tumours and postlobectomy. OUTCOME MEASURES: Fatty liver was diagnosed according to echogenic findings. NAFLD included grades 1-3 fatty liver and high-degree NAFLD defined grades 2-3 fatty liver. RESULTS: 580 males and 774 females with a mean age of 47.2 (SD=16.1) years were cross-sectionally studied. The participants with NAFLD have significantly higher levels of ALT/AST ratio, fasting glucose, triglyceride and systolic/diastolic blood pressure than non-NAFLD participants. The association between NAFLD and ALT/AST was significant even when adjusting for the metabolic syndrome (aOR 1.90; 95% CI 1.37 to 2.65; p<0.001). In patients with a high degree of NAFLD, the ALT/AST ratio was still a significant predictor for hepatosteatosis (aOR 2.44; 95% CI 1.58 to 3.77; p<0.001). CONCLUSIONS: The ALT/AST ratio could be a strong risk of hepatosteatosis in patients with chronic HCV infection. PMID- 26369805 TI - Early post-mortem formation of carbonate concretions around tusk-shells over week month timescales. AB - Carbonate concretions occur in sedimentary rocks of widely varying geological ages throughout the world. Many of these concretions are isolated spheres, centered on fossils. The formation of such concretions has been variously explained by diffusion of inorganic carbon and organic matter in buried marine sediments. However, details of the syn-depositional chemical processes by which the isolated spherical shape developed and the associated carbon sources are little known. Here we present evidence that spherical carbonate concretions (diameters phi : 14 ~ 37 mm) around tusk-shells (Fissidentalium spp.) were formed within weeks or months following death of the organism by the seepage of fatty acid from decaying soft body tissues. Characteristic concentrations of carbonate around the mouth of a tusk-shell reveal very rapid formation during the decay of organic matter from the tusk-shell. Available observations and geochemical evidence have enabled us to construct a 'Diffusion-growth rate cross-plot' that can be used to estimate the growth rate of all kinds of isolated spherical carbonate concretions identified in marine formations. Results shown here suggest that isolated spherical concretions that are not associated with fossils might also be formed from carbon sourced in the decaying soft body tissues of non skeletal organisms with otherwise low preservation potential. PMID- 26369803 TI - Individual-level and community-level effect modifiers of the temperature mortality relationship in 66 Chinese communities. AB - OBJECTIVES: To examine the modification of temperature-mortality association by factors at the individual and community levels. DESIGN AND METHODS: This study investigated this issue using a national database comprising daily data of 66 Chinese communities for 2006-2011. A 'threshold-natural cubic spline' distributed lag non-linear model was utilised to estimate the mortality effects of daily mean temperature, and then examined the modification of the relationship by individual factors (age, sex, education level, place of death and cause of death) using a meta-analysis approach and community-level factors (annual temperature, population density, sex ratio, percentage of older population, health access, household income and latitude) using a meta-regression method. RESULTS: We found significant effects of high and low temperatures on mortality in China. The pooled excess mortality risk was 1.04% (95% CI 0.90% to 1.18%) for a 1 degrees C temperature decrease below the minimum mortality temperature (MMT), and 3.44% (95% CI 3.00% to 3.88%) for a 1 degrees C temperature increase above MMT. At the individual level, age and place of death were found to be significant modifiers of cold effect, while age, sex, place of death, cause of death and education level were effect modifiers of heat effect. At the community level, communities with lower socioeconomic status and higher annual temperature were generally more vulnerable to the mortality effects of high and low temperatures. CONCLUSIONS: This study identifies susceptibility based on both individual-level and community level effect modifiers; more attention should be given to these vulnerable individuals and communities to reduce adverse health effects of extreme temperatures. PMID- 26369806 TI - Circles of Support and Accountability for Sex Offenders: A Systematic Review of Outcomes. AB - We conducted a systematic review of studies reporting on the effectiveness of Circles of Support and Accountability (Circles). Circles use volunteers to provide support for sex offenders living in the community. We searched 10 databases up to the end of 2013 and identified 3 relevant outcome studies. An additional 12 papers or reports were identified by searching reference lists, Google, and contacting key authors and Circles providers to obtain unpublished data. These 15 studies comprised one randomized controlled trial, three retrospective cohorts with matched controls, and 11 case series. The majority reported measures of recidivism, particularly reconviction. The 4 studies with controls generally reported that participation in Circles was associated with lower recidivism although there were few statistically significant differences. Few studies examined changes in risk or psychosocial outcomes. A number of methodological issues are discussed. Longer term, prospective follow-up studies with control groups are required to address these issues. PMID- 26369804 TI - Epithelial to mesenchymal transition in the liver field: the double face of Everolimus in vitro. AB - BACKGROUND: Everolimus (EVE), a mammalian target of rapamycin inhibitor, has been proposed as liver transplant immunosuppressive drug, gaining wide interest also for the treatment of cancer. Although an appropriate tolerance, it may induce several adverse effects, such as fibro-interstitial pneumonitis due to the acquisition of activated myofibroblasts. The exact molecular mechanism associated with epithelial to mesenchymal transition (EMT) may be crucial also in the liver context. This work examines the role and the molecular mediators of EMT in hepatic stellate cell (HSC) and human liver cancer cells (HepG2) and the potential role of EVE to maintain the epithelial phenotype rather than to act as a potential initiators of EMT. METHODS: Real time-PCR and western blot have been used to assess the capability of EVE at low-therapeutic (10 nM) and high (100 nM) dose to induce an in vitro EMT in HSC and HepG2. RESULTS: Biomolecular experiments demonstrated that low concentration of EVE (10 nM) did not modify the gene expression of alpha-smooth muscle actin (alpha-SMA), Vimentin (VIM), Fibronectin (FN) in both HSC and HepG2 cells, whereas EVE at 100 nM induced a significant over-expression of all the three above-mentioned genes and an increment of alpha-SMA and FN protein levels. Additionally, 100 nM of EVE induced a significant phosphorylation of AKT and an up-regulation of TGF-beta expression in HSC and HepG2 cells. DISCUSSION: Our data, although obtained in an in vitro model, revealed, for the first time, that high concentration of EVE may induce EMT in liver cells confirming previous published evidences obtained in renal cells. Additionally, they suggested that mTOR-I should be administered at the lowest dose able to maximize their important and specific therapeutic properties minimizing or avoiding fibrosis-related adverse effects. CONCLUSIONS: In summary, if confirmed by additional studies, our results could be useful for researchers to standardize new therapeutic immunosuppressive and anticancer drugs protocols. PMID- 26369807 TI - Prospective study of nephrolithiasis occurrence in children receiving cefotriaxone. AB - AIM: Ceftriaxone is a commonly used antibiotic among the paediatric population. Various reports have associated high doses of Ceftriaxone with the development of nephrolithiasis; our aim was to test this association with a 5 day course of treatment. METHODS: Our study group consisted of 120 patients divided into two groups. The first group included 60 patients who underwent treatment with Ceftriaxone therapy that was started empirically and continued for 5 days at the dose of 80 mg/kg per day. The second group (60 patients) who received treatment with other antibiotics (other than Ceftriaxone), as recommended by hospital protocols. Patients with urinary tract infections (UTI) were excluded as UTI may be a predisposing cause for nephrolithiasis. Baseline and follow up after 5 days were done with; abdominal ultrasound, serum urea, creatinine, serum calcium, 24 h urinary calcium and urinary calcium/ creatinine ratio. Extended metabolic tests were done for cases that developed nephrolithiasis. RESULTS: Five cases out of the 60 patients treated with Ceftriaxone developed calculi; that were small and were eliminated spontaneously in four cases at mean duration of 3 weeks. In these cases renal ultrasonography examinations were normal prior to treatment; and none of them had metabolic disturbances or risk factors leading to stone formation. By multiple regression analysis, only age was related to nephrolithiasis formation being higher in the group that has developed stones. CONCLUSION: Only patients who underwent Ceftriaxone therapy have developed renal stones, even with a short course of therapy (5 days), and in the absence of a known predisposing cause for nephrolithiasis. We have thus concluded that Ceftriaxone by itself maybe a predisposing factor for nephrolithiasis. PMID- 26369808 TI - Avemar and Echinacea extracts enhance mobilization and homing of CD34(+) stem cells in rats with acute myocardial infarction. AB - INTRODUCTION: Activation of endogenous stem cell mobilization can contribute to myocardial regeneration after ischemic injury. This study aimed to evaluate the possible role of Avemar or Echinacea extracts in inducing mobilization and homing of CD34(+) stem cells in relation to the inflammatory and hematopoietic cytokines in rats suffering from acute myocardial infarction (AMI). METHODS: AMI was developed by two consecutive subcutaneous injections of isoprenaline (85 mg/kg). AMI rats were either post-treated or pre- and post-treated daily with oral doses of Avemar (121 mg/kg) or Echinacea (130 mg/kg). In whole blood, the number of CD34(+) cells was measured by flow cytometry and their homing to the myocardium was immunohistochemically assessed. Serum creatine kinase, vascular endothelial growth factor, interleukin-8 and granulocyte macrophage colony stimulating factor were determined on days 1, 7 and 14 after AMI. Sections of the myocardium were histopathologically assessed. RESULTS: Rats pre- and post-treated with Avemar or Echinacea exhibited substantial increases in the number of circulating CD34(+) cells, peaking on the first day after AMI to approximately 13-fold and 15-fold, respectively, with a decline in their level on day 7 followed by a significant increase on day 14 compared to their corresponding AMI levels. Only post treatment with Echinacea caused a time-dependent increase in circulating CD34(+) cells on days 7 and 14. Such increases in circulating CD34(+) cells were accompanied by increased homing to myocardial tissue 14 days after AMI. Interestingly, pre- and post-treatment with Avemar or Echinacea substantially increased serum creatine kinase on day 1, normalized its activity on day 7 and, on continued treatment, only Echinacea markedly increased its activity on day 14 compared to the corresponding AMI values. Moreover, both treatments modified differently the elevated serum vascular endothelial growth factor and the lowered granulocyte macrophage colony stimulating factor levels of the AMI group but did not affect the level of interleukin-8. These results were supported histopathologically by reduced inflammatory reactions and enhanced neovascularization. CONCLUSION: Avemar and Echinacea extracts can effectively induce mobilization and homing of CD34(+) stem cells to the myocardial tissue and thus may help in stem cell-based regeneration of the infarcted myocardium. PMID- 26369809 TI - Shrinking the language accessibility gap: a mixed methods evaluation of telephone interpretation services in a large, diverse urban health care system. AB - INTRODUCTION: Language interpretation services for patients who are not proficient in a country's official language(s) are essential for improving health equity across diverse populations, and achieving clinical safety and quality for both patients and providers. Nevertheless, overall use of these services remains low, regardless of how they are delivered. In Toronto, Ontario, one of the most ethnically diverse urban centres, the regional local health integration network which oversees the highest concentration of health care organizations servicing 1.2 million residents, partnered with key stakeholders to make Over-the-Phone (OPI) interpretation services broadly and economically available in 170 different languages to its diverse network of health care organizations. This evaluation aimed to assess patients' and providers' experiences with OPI in these varied settings and the impact (if any) on alternative interpretation services and on health service delivery access and quality. METHODS: This study used a two-phased sequential exploratory mixed-methods approach to evaluate the initiative. Phase I was comprised of semi-structured interviews with representatives from the program stakeholders; these findings were applied to identify appropriate survey questions and response categories, and provided context and depth of understanding to Phase II results. Phase II included web-based and self administered surveys for both providers and patients engaging with OPI. RESULTS: Both providers and patients identified a broad range of positive impacts OPI had on health care service delivery quality and access, and high levels of satisfaction with OPI, in a variety of health care settings. Providers also revealed a marked decrease in the use of ad-hoc, nonprofessional strategies for interpretation after the implementation of OPI, and noted it had either no impact on their workload or had decreased it overall. CONCLUSIONS: OPI is clearly not the sole answer to the complex array of health care needs and access gaps that exist for persons without proficiency in their country's official language. Nevertheless, this evaluation provides compelling evidence that OPI is a valuable component, and that it may contribute to a broader range of positive impacts, and within a broader range of health care settings, than previously explored. PMID- 26369810 TI - Engineering E. coli-E. coli cocultures for production of muconic acid from glycerol. AB - BACKGROUND: cis, cis-Muconic acid is an important chemical that can be biosynthesized from simple substrates in engineered microorganisms. Recently, it has been shown that engineering microbial cocultures is an emerging and promising approach for biochemical production. In this study, we aim to explore the potential of the E. coli-E. coli coculture system to use a single renewable carbon source, glycerol, for the production of value-added product cis, cis muconic acid. RESULTS: Two coculture engineering strategies were investigated. In the first strategy, an E. coli strain containing the complete biosynthesis pathway was co-cultivated with another E. coli strain containing only a heterologous intermediate-to-product biosynthetic pathway. In the second strategy, the upstream and downstream pathways were accommodated in two separate E. coli strains, each of which was dedicated to one portion of the biosynthesis process. Compared with the monoculture approach, both coculture engineering strategies improved the production significantly. Using a batch bioreactor, the engineered coculture achieved a 2 g/L muconic acid production with a yield of 0.1 g/g. CONCLUSIONS: Our results demonstrate that coculture engineering is a viable option for producing muconic acid from glycerol. Moreover, microbial coculture systems are shown to have the potential for converting single carbon source to value-added products. PMID- 26369811 TI - Carbazole Scaffold in Medicinal Chemistry and Natural Products: A Review from 2010-2015. AB - 9H-carbazole is an aromatic molecule that is tricyclic in nature, with two benzene rings fused onto a 5-membered pyrrole ring. Obtained from natural sources or by synthetic routes, this scaffold has gained much interest due to its wide range of biological activity upon modifications, including antibacterial, antimalarial, anticancer, and anti-Alzheimer properties. This review reports a survey of the literature on carbazole-containing molecules and their medicinal activities from 2010 through 2015. In particular, we focus on their in vitro and in vivo activities and summarize structure-activity relationships (SAR), mechanisms of action, and/or cytotoxicity/selectivity findings when available to provide future guidance for the development of clinically useful agents from this template. PMID- 26369812 TI - Short Antimicrobial Peptides and Peptide Scaffolds as Promising Antibacterial Agents. AB - Antimicrobial peptides have recently garnered significant attention as an emerging source of potential antibiotics, due to the swift emergence of multidrug resistant bacteria and a dwindling antibiotic pipeline. The vast majority of antimicrobial peptides are long, comprised of more than 10 amino acids, resulting in significant production costs for their synthesis while simultaneously displaying metabolic instability and relatively poor pharmacological profiles. To counter these problems, efforts have been shifted to shorter molecules and the development of new peptidomimetic approaches. In this paper, we review promising short, naturally-isolated or synthetic, antimicrobial peptides, along with their mimics, and discuss their merits as potential antibacterial agents. PMID- 26369813 TI - A Recent Perspective on Discovery and Development of Diverse Therapeutic Agents Inspired from Isatin Alkaloids. AB - Isatin as an alkaloidal framework have consistently attracted attention of medicinal chemist towards development of wide range of novel therapeutic agents. This review report has discussed significant isatin lead molecules and their derivatives which have shown promising biological potential in recent times. The substituted isatins showing a potent pharmacological activities such as antimicrobial, antitubercular, anticancer, antioxidant, anti-histaminic, anti HIV, antiviral, anti-inflammatory, anti-Parkinson's and antidiabetic have been described in this review. The mechanism of action leading to therapeutic activity of the respective isatin derivation has also been recorded. This review reveals that the systematic and rational modifications on isatin motif exhibited significant bio-activities which can be exploited for the development of potent novel therapeutic agents in the future studies. Hence the quest to investigate more structural alterations on isatin scaffold should be continued. PMID- 26369814 TI - Base-Modified Nucleosides as Chemotherapeutic Agents: Past and Future. AB - Nucleoside and nucleobase antimetabolites have substantially impacted treatment of cancer and infections. Their close resemblance to natural analogs gives them the power to interfere with a variety of intracellular targets, which on one hand gives them high potency, but on the other hand incurs severe side effects, especially of the chemotherapeutics used against malignancies. Therefore, the development of novel nucleoside analogs with widened therapeutic windows represents an attractive target to synthetic organic and medicinal chemists. This review discusses the current antimetabolite drugs: 5- fluorouracil, 6 mercaptopurine, 6-thioguanine, Cladribine, Vidaza, Decitabine, Emtricitabine, Abacavir, Sorivudine, Clofarabine, Fludarabine, and Nelarabine; gives insight into the nucleoside drug candidates that are being developed; and outlines the approaches to nucleobase modifications that may help discover novel bioactive nucleoside analogs with the mechanism of action focused on termination of DNA synthesis, which is expected to diminish the off-target toxicity in non proliferating human cells. PMID- 26369815 TI - Sulfur Containing Scaffolds in Drugs: Synthesis and Application in Medicinal Chemistry. AB - The impact of the development of sulfur therapeutics is instrumental to the evolution of the pharmaceutical industry. Sulfur-derived functional groups can be found in a broad range of pharmaceuticals and natural products. For centuries, sulfur continues to maintain its status as the dominating heteroatom integrated into a set of 362 sulfur-containing FDA approved drugs (besides oxygen or nitrogen) through the present. Sulfonamides, thioethers, sulfones and Penicillin are the most common scaffolds in sulfur containing drugs, which are well studied both on synthesis and application during the past decades. In this review, these four moieties in pharmaceuticals and recent advances in the synthesis of the corresponding core scaffolds are presented. PMID- 26369816 TI - The Roles of Vitamin D and Its Analogs in Inflammatory Diseases. AB - The discovery of nonclassical actions, other than mineral homeostasis, of 1alpha,25- dihydroxyvitamin D3 (1,25D3) has expanded its applications. Among these, its anti-inflammation activity has drawn more and more attention of researchers to investigate its role in regulating the progression of inflammatory diseases. The expression of many inflammation-related genes is regulated by 1,25D3 through vitamin D receptor (VDR) in a large variety of cells including immune cells such as, but not limited to, macrophages, dendritic cells, T helper cells, and B cells. Studies of 1,25D3 in these immune cells have shown both direct and indirect immunomodulatory activities affecting innate and adaptive immune responses. Moreover, 1,25D3 can also exert its anti-inflammation effects through regulating the biosynthesis of pro-inflammatory molecules in the prostaglandin pathway or through nuclear factor kappa light-chain-enhancer of activated B cells (NFkappaB) by affecting cytokine production and inflammatory responses. These actions of 1,25D3 may explain the associations between vitamin D levels and inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, asthma, type 1 diabetes, and systemic lupus erythematosus. Although several analogs of 1,25D3 have shown potent immunomodulatory or anti-inflammatory activity on immune cell cultures or in animal models, no vitamin D analog has been used in clinical research to treat inflammatory diseases. Here, we review the relationship between vitamin D analogs and inflammation based on observations of immune cells, prostaglandin and NFkappaB pathways, as well as common inflammatory diseases. PMID- 26369817 TI - Bispidine as a Privileged Scaffold. AB - Thediazabicyclic molecule bispidine named by the chemist Carl Mannich in 1930, is a naturally occurring scaffold with interesting features. Bispidine can form different conformers, has high basicity, can attack dichloromethane, has metal ion coordination properties and interacts with nicotinic acetylcholine receptors. In this review we will discuss important properties, synthetic pathways and biological activities of bispidine and some derivatives. Bispidine can function as a scaffold for compounds with very diverse biological activities, e.g. interacting with ion channels, G-protein coupled receptors, and enzymes, and is even used for the development of new in vivo radiotracers. PMID- 26369818 TI - Cellular Selenoprotein mRNA Tethering via Antisense Interactions with Ebola and HIV-1 mRNAs May Impact Host Selenium Biochemistry. AB - Regulation of protein expression by non-coding RNAs typically involves effects on mRNA degradation and/or ribosomal translation. The possibility of virus-host mRNA mRNA antisense tethering interactions (ATI) as a gain-of-function strategy, via the capture of functional RNA motifs, has not been hitherto considered. We present evidence that ATIs may be exploited by certain RNA viruses in order to tether the mRNAs of host selenoproteins, potentially exploiting the proximity of a captured host selenocysteine insertion sequence (SECIS) element to enable the expression of virally-encoded selenoprotein modules, via translation of in-frame UGA stop codons as selenocysteine. Computational analysis predicts thermodynamically stable ATIs between several widely expressed mammalian selenoprotein mRNAs (e.g., isoforms of thioredoxin reductase) and specific Ebola virus mRNAs, and HIV-1 mRNA, which we demonstrate via DNA gel shift assays. The probable functional significance of these ATIs is further supported by the observation that, in both viruses, they are located in close proximity to highly conserved in-frame UGA stop codons at the 3' end of open reading frames that encode essential viral proteins (the HIV-1 nef protein and the Ebola nucleoprotein). Significantly, in HIV/AIDS patients, an inverse correlation between serum selenium and mortality has been repeatedly documented, and clinical benefits of selenium in the context of multi-micronutrient supplementation have been demonstrated in several well-controlled clinical trials. Hence, in the light of our findings, the possibility of a similar role for selenium in Ebola pathogenesis and treatment merits serious investigation. PMID- 26369819 TI - Development of Trypsin-Like Serine Protease Inhibitors as Therapeutic Agents: Opportunities, Challenges, and their Unique Structure-Based Rationales. AB - There has been a revolution in the development of effective, small-molecule anticoagulants and antiplatelet agents. Numerous trypsin-like serine proteases have been under active pursuit as therapeutic targets. Important examples include thrombin, factor VIIa, factor Xa, and beta-tryptase with indications ranging from thrombosis and inflammation to asthma and chronic obstructive pulmonary disease (COPD). Trypsin-like serine proteases exhibit a highly similar tertiary folding pattern, especially for the region near the substrate binding pocket that includes the conserved catalytic triad consisting of histidine 57, aspartic acid 102, and serine 195. A rich collection of X-ray structures for many trypsin-like serine proteases is available, which greatly facilitated the optimization of small organic inhibitors as therapeutic agents. The present review surveyed those inhibitors disclosed in peer-reviewed scientific journals and patent publications with a special focus on structural features and protein-inhibitor interactions that implicated the inhibitor optimization process. The role played by the residue 190 of trypsin-like serine proteases is critical. While many inhibitors without a basic group have progressed into the clinic for ones with alanine 190, the task for those with serine 190 remains extremely challenging, if not impossible. In addition to warfarin, heparin, and low molecular weight heparins (LMWHs), treatment options have expanded with the development and approval of the new oral anticoagulants (NOACs). The NOACs are superior to vitamin K antagonists in terms of rapid onset, pharmacokinetics, drug/food interactions, and regular coagulation monitoring; but one serious drawback is the lack of an effective antidote at this time. Apixaban (Eliquis), rivaroxaban (Xarelto), and edoxaban (Savaysa) are the new Xa inhibitors that have been recently approved by the U.S. FDA and are in current clinical practice. These drugs bind to the active site of factor Xa (fXa) which prevents the conversion of prothrombin to thrombin. In addition, dabigatran etexikate (Pradaxa), the direct thrombin inhibitor (fIIa) is also now widely prescribed. PMID- 26369820 TI - G Protein Coupled Receptors And Structure-Based Advances. AB - G protein coupled receptors (GPCRs) are membrane proteins coupled with G proteins through which they transmit signals to the cytoplasm. Approximately 30% of pharmaceuticals target these receptors, even though crystal structures were scarce at the time. Furthermore, an additional 15% of GPCRs have yet to be exploited for therapeutic intervention. An overview of structural information is presented, with emphasis on rearrangements occurring during activation,in light of recently resolved activated state crystal structures. Computational efforts over recent years are also highlighted. PMID- 26369821 TI - Methionine AminoPeptidase Type-2 Inhibitors Targeting Angiogenesis. AB - Angiogenesis has been identified as a crucial process in the development and spread of cancers. There are many regulators of angiogenesis which are not yet fully understood. Methionine aminiopeptidase is a metalloenzyme with two structurally distinct forms in humans, Type-1 (MetAP-1) and Type-2 (MetAP-2). It has been shown that small molecule inhibitors of MetAP-2 suppress endothelial cell proliferation. The initial discovery by Donald Ingber of MetAP-2 inhibition as a potential target in angiogenesis began with a fortuitous observation similar to the discovery of penicillin activity by Sir Alexander Fleming. From a drug design perspective, MetAP-2 is an attractive target. Fumagillin and ovalicin, known natural products, bind with IC50 values in low nanomolar concentrations. Crystal structures of the bound complexes provide 3-dimensional coordinates for advanced computational studies. More recent discoveries have shown other biological activities for MetAP-2 inhibition, which has generated new interests in the design of novel inhibitors. Semisynthetic fumagillin derivatives such as AGM-1470 (TNP-470) have been shown to have better drug properties, but have not been very successful in clinical trials. The rationale and development of novel multicyclic analogs of fumagillin are reviewed. PMID- 26369822 TI - Receptor-based 3D-QSAR in Drug Design: Methods and Applications in Kinase Studies. AB - Receptor-based 3D-QSAR strategy represents a superior integration of structure based drug design (SBDD) and three-dimensional quantitative structure-activity relationship (3D-QSAR) analysis. It combines the accurate prediction of ligand poses by the SBDD approach with the good predictability and interpretability of statistical models derived from the 3D-QSAR approach. Extensive efforts have been devoted to the development of receptor-based 3D-QSAR methods and two alternative approaches have been exploited. One associates with computing the binding interactions between a receptor and a ligand to generate structure-based descriptors for QSAR analyses. The other concerns the application of various docking protocols to generate optimal ligand poses so as to provide reliable molecular alignments for the conventional 3D-QSAR operations. This review highlights new concepts and methodologies recently developed in the field of receptorbased 3D-QSAR, and in particular, covers its application in kinase studies. PMID- 26369823 TI - Cheminfomatic-based Drug Discovery of Human Tyrosine Kinase Inhibitors. AB - Receptor Tyrosine Kinases (RTKs) are essential components for regulating cell cell signaling and communication events in cell growth, proliferation, differentiation, survival and metabolism. Deregulation of RTKs and their associated signaling pathways can lead to a wide variety of human diseases such as immunodeficiency, diabetes, arterosclerosis, psoriasis and cancer. Thus RTKs have become one of the most important drug targets families in recent decade. Pharmaceutical companies have dedicated their research efforts towards the discovery of small-molecule inhibitors of RTKs, many of which had been approved by the U.S. Food and Drug Administration (US FDA) or are currently in clinical trials. The great successes in the development of small-molecule inhibitors of RTKs are largely attributed to the use of modern cheminformatic approaches to identifying lead scaffolds. Those include the quantitative structure-activity relationship (QSAR) modeling, as well as the structure-, and ligand-based pharmacophore modeling techniques in this case. Herein we inspected the literature thoroughly in an effort to conduct a comparative analysis of major findings regarding the essential structure-activity relationships (SARs)/pharmacophore features of known active RTK inhibitors, most of which were collected from cheminformatic modeling approaches. PMID- 26369824 TI - Drug Design Targeting the CXCR4/CXCR7/CXCL12 Pathway. AB - Under physiological conditions, CXCL12 modulates cell proliferation, survival, angiogenesis, and migration mainly through CXCR4. Interestingly, the newly discovered receptor CXCR7 for CXCL12 is highly expressed in many tumor cells as well as tumor-associated blood vessels, although the level of CXCR7 in normal blood cells is low. Recently, many studies have suggested that CXCR7 promotes cell growth and metastasis in various cancers, including lymphoma and leukemia, hepatocecullar, ovarian, colorectal, breast and lung cancer. Compared to CXCR4, CXCR7 is a non-classical GPCR that is unable to activate G proteins. The function of CXCR7 is generally considered to be mediated by: (a) recruiting beta-arrestin 2; (b) heterodimerizing with CXCR4; and (c) acting as a "scavenger" of CXCL12, thus lowering the level of CXCL12 to weaken the activity of CXCR4. However, the crosstalk between CXCL12/CXCR7/CXCR4 and other signaling pathways (such as the p38 MAPK pathway, the PI3K/mTOR pathway, the STAT3 signaling, and metalloproteinases MMP-9 and MMP-2) is more complicated. The function of CXCR7 is also involved in modulating tumor microenvironment, tumor cell migration and apoptosis. Understanding these complex interactions will provide insight in drug design targeting the CXCR7 as potential anticancer therapy. PMID- 26369825 TI - Targeting the Atypical Chemokine Receptor ACKR3/CXCR7: Phase 1 - Phage Display Peptide Identification and Characterization. AB - One of the greatest challenges in fighting cancer is cell targeting and biomarker selection. The Atypical Chemokine Receptor ACKR3/CXCR7 is expressed on many cancer cell types, including breast cancer and glioblastoma, and binds the endogenous ligands SDF1/CXCL12 and ITAC/CXCL11. A 20 amino acid region of the ACKR3/CXCR7 N-terminus was synthesized and targeted with the NEB PhD-7 Phage Display Peptide Library. Twenty-nine phages were isolated and heptapeptide inserts sequenced; of these, 23 sequences were unique. A 3D molecular model was created for the ACKR3/CXCR7 N-terminus by mutating the corresponding region of the crystal structure of CXCR4 with bound SDF1/CXCL12. A ClustalW alignment was performed on each peptide sequence using the entire SDF1/CXCL12 sequence as the template. The 23-peptide sequences showed similarity to three distinct regions of the SDF1/CXCL12 molecule. A 3D molecular model was made for each of the phage peptide inserts to visually identify potential areas of steric interference of peptides that simulated CXCL12 regions not in contact with the receptor's Nterminus. An ELISA analysis of the relative binding affinity between the peptides identified 9 peptides with statistically significant results. The candidate pool of 9 peptides was further reduced to 3 peptides based on their affinity for the targeted N-terminus region peptide versus no target peptide present or a scrambled negative control peptide. The results clearly show the Phage Display protocol can be used to target a synthesized region of the ACKR3/CXCR7 N-terminus. The 3 peptides chosen, P20, P3, and P9, will be the basis for further targeting studies. PMID- 26369826 TI - Advances in the Development of Class I Phosphoinositide 3-Kinase (PI3K) Inhibitors. AB - The PI3K signaling cascade is the key moderator of cell proliferation, survival, motility, and apoptosis. Class I PI3K proteins are well characterized and linked to thrombosis (PI3Kbeta), rheumatoid arthritis (PI3Kdelta), and cancer (PI3Kalpha). In this review, we explore the latest progress in the design and development of selective Class I PI3K inhibitors from the perspective of drug design and structure activity relationships. PMID- 26369827 TI - The prognostic value of Tiam1 protein expression in head and neck squamous cell carcinoma: a retrospective study. AB - INTRODUCTION: Head and neck squamous cell carcinoma (HNSCC) is a common cancer worldwide and has a poor prognosis. A biomarker predicting the clinical outcome of HNSCC patients could be useful in guiding treatment planning. Overexpression of the T lymphoma invasion and metastasis 1 (Tiam1) protein has been implicated in the migration and invasion of neoplasms. However, its role in HNSCC progression needs to be further validated. We detected the expression of Tiam1 in normal and tumor tissues and determined its association with clinical outcomes in patients with HNSCC. METHODS: We measured the expression of Tiam1 in normal and cancerous tissue samples from the patients with HNSCC treated at Sun Yat-sen University Cancer Center between 2001 and 2008. The Tiam1 expression was scored from 0 to 12 based on the percentage of positively stained cells and the staining intensity. We then determined the diagnostic performance of this score in predicting overall survival (OS) and disease-free survival (DFS). RESULTS: Of the 194 evaluable patients, those with advanced disease, lymph node metastasis at diagnosis, and recurrence or metastasis during follow-up had a higher tendency of having high Tiam1 expression as compared with their counterparts (P < 0.05). The proportion of samples with high Tiam1 expression was also higher in cancerous tissues than in non-cancerous tissues (57.7% vs. 13.9%, P < 0.001). Cox proportional hazards regression analysis revealed that Tiam1 expression scores of 5 and greater independently predicted short OS and DFS. CONCLUSION: The Tiam1 expression is shown as a promising biomarker of clinical outcomes in patients with HNSCC and should be evaluated in prospective trials. PMID- 26369828 TI - The Michigan Appropriateness Guide for Intravenous Catheters (MAGIC): Results From a Multispecialty Panel Using the RAND/UCLA Appropriateness Method. AB - Use of peripherally inserted central catheters (PICCs) has grown substantially in recent years. Increasing use has led to the realization that PICCs are associated with important complications, including thrombosis and infection. Moreover, some PICCs may not be placed for clinically valid reasons. Defining appropriate indications for insertion, maintenance, and care of PICCs is thus important for patient safety. An international panel was convened that applied the RAND/UCLA Appropriateness Method to develop criteria for use of PICCs. After systematic reviews of the literature, scenarios related to PICC use, care, and maintenance were developed according to patient population (for example, general hospitalized, critically ill, cancer, kidney disease), indication for insertion (infusion of peripherally compatible infusates vs. vesicants), and duration of use (<=5 days, 6 to 14 days, 15 to 30 days, or >=31 days). Within each scenario, appropriateness of PICC use was compared with that of other venous access devices. After review of 665 scenarios, 253 (38%) were rated as appropriate, 124 (19%) as neutral/uncertain, and 288 (43%) as inappropriate. For peripherally compatible infusions, PICC use was rated as inappropriate when the proposed duration of use was 5 or fewer days. Midline catheters and ultrasonography-guided peripheral intravenous catheters were preferred to PICCs for use between 6 and 14 days. In critically ill patients, nontunneled central venous catheters were preferred over PICCs when 14 or fewer days of use were likely. In patients with cancer, PICCs were rated as appropriate for irritant or vesicant infusion, regardless of duration. The panel of experts used a validated method to develop appropriate indications for PICC use across patient populations. These criteria can be used to improve care, inform quality improvement efforts, and advance the safety of medical patients. PMID- 26369829 TI - Effectiveness of azacitidine for the treatment of higher-risk myelodysplastic syndromes in daily practice: results from the Dutch population-based PHAROS MDS registry. PMID- 26369830 TI - The different effects of neighbourhood and individual social capital on health compromising behaviours in women during pregnancy: a multi-level analysis. AB - BACKGROUND: This study assessed clustering of three health-compromising behaviours and explored the association of neighbourhood and individual social capital with simultaneous health-compromising behaviours and patterns of those behaviours in women in the first trimester of pregnancy (baseline) and during the second and third trimesters of pregnancy (follow-up). METHODS: A longitudinal study was conducted on a representative sample of women recruited in antenatal care units grouped in 46 neighbourhoods from Brazil. Neighbourhood-level measures (social capital and socioeconomic status), individual social capital (social support and social networks) and socio-demographic variables were collected at baseline. Smoking, alcohol consumption and inadequate diet were assessed at baseline and follow-up. Clustering was assessed using an observed to expected ratio method. The association of contextual and individual social capital with the health-compromising behaviours outcomes was analyzed through multilevel multivariate regression models. RESULTS: Clustering of the three health compromising behaviours as well as of smoking and alcohol consumption were identified at both baseline and follow-up periods. Neighbourhood social capital did not influence the occurrence of simultaneous health-compromising behaviours. More health-compromising behaviours in both periods was inversely associated with low levels of individual social capital. Low individual social capital predicted smoking during whole pregnancy, while high individual social capital increased the likelihood of stopping smoking and improving diet during pregnancy. Maintaining an inadequate diet during pregnancy was influenced by low individual and neighbourhood social capital. CONCLUSIONS: Three health-compromising behaviours are relatively common and cluster in Brazilian women throughout pregnancy. Low individual social capital significantly predicted simultaneous health-compromising behaviours and patterns of smoking and inadequate diet during pregnancy while low neighbourhood social capital was only relevant for inadequate diet. These findings suggest that interventions focusing on reducing multiple behaviours should be part of antenatal care throughout pregnancy. Individual and contextual social resources should be considered when planning the interventions. PMID- 26369831 TI - Conditional deletion of nonmuscle myosin II-A in mouse tongue epithelium results in squamous cell carcinoma. AB - To investigate the contribution of nonmuscle myosin II-A (NM II-A) to early cardiac development we crossed Myh9 floxed mice and Nkx2.5 cre-recombinase mice. Nkx2.5 is expressed in the early heart (E7.5) and later in the tongue epithelium. Mice homozygous for deletion of NM II-A (A(Nkx)/A(Nkx)) are born at the expected ratio with normal hearts, but consistently develop an invasive squamous cell carcinoma (SCC) of the tongue (32/32 A(Nkx)/A(Nkx)) as early as E17.5. To assess reproducibility a second, independent line of Myh9 floxed mice derived from a different embryonic stem cell clone was tested. This second line also develops SCC indistinguishable from the first (15/15). In A(Nkx)/A(Nkx) mouse tongue epithelium, genetic deletion of NM II-A does not affect stabilization of TP53, unlike a previous report for SCC. We attribute the consistent, early formation of SCC with high penetrance to the role of NM II in maintaining mitotic stability during karyokinesis. PMID- 26369832 TI - OPN gene polymorphisms, rs17524488 GG/G, rs11730582 T/C, and rs9138 C/A, and cancer risk in a Chinese population. AB - Previous studies have investigated the association between osteopontin (OPN) gene polymorphisms, rs17524488 (-156 GG/G), rs11730582 (-443 T/C), and rs9138 (C/A) and cancer risk in the Chinese population. However, the results are controversial and indefinite. We therefore carried out a meta-analysis to derive a more precise estimation of these associations. The PubMed database was systematically searched to identify potentially eligible reports. Crude odds ratios (OR) and 95% confidence intervals (CI) were used to assess the strength of associations between 3 OPN gene polymorphisms and cancer risk in a Chinese population. A total of 10 articles involving 2,391 cases and 3,007 controls were evaluated. The pooled OR indicated that OPN rs17524488 (-156 GG/G) polymorphism was significantly associated with cancer risk in Chinese population. In a stratified analysis by source of control, significant associations were also observed among rs17524488 (-156 GG/G) and rs11730582 (-443 T/C) polymorphisms and cancer. In addition, a stronger association was observed between rs9138 (C/A) polymorphism and cancer risk. In conclusion, this meta-analysis suggests that OPN rs17524488 ( 156 GG/G), rs11730582 (-443 T/C), and rs9138 (C/A) polymorphisms may be associated with cancer susceptibility in the Chinese population. Nevertheless, further investigation on a larger population covering different ethnicities are warranted. PMID- 26369834 TI - Dosimetric effects of roll rotational setup errors on lung stereotactic ablative radiotherapy using volumetric modulated arc therapy. AB - OBJECTIVE: To evaluate the dosimetric effects of roll-rotational setup errors of stereotactic ablative radiotherapy (SABR) for lung cancer using volumetric modulated arc therapy (VMAT). METHODS: A total of 23 lung SABR cases were evaluated retrospectively. Each of the planning CT images was intentionally rotated by +/-1 degrees , +/-2 degrees and +/-3 degrees . After that, to simulate the translational couch correction, rotated CT images were moved along the x, y and z axis to match the centroid of the target volume in the rotated CT images with that in the original CT images. The differences in D95% and V100% of the target volume, D0.35cc of spinal cord, D0.35cc and D5cc of oesophagus and V20Gy of lung between the original and the rotated CT images were calculated. RESULTS: The average differences in D95% and V100% of target volume, D0.35cc of spinal cord, D0.35cc and D5cc of oesophagus and V20Gy of lung were -0.3% +/- 0.4% and -0.7% +/- 2.4%, 1.6 +/- 27.9 cGy, -1.6 +/- 37.6 cGy, 15.9 +/- 25.3 cGy and 0.0% +/- 0.1%, respectively. The dosimetric changes in organs at risk (OARs) near the target volume were sometimes considerable due to roll-rotational setup errors, despite the translational correction, and those were patient specific. CONCLUSION: In the case of coplanar VMAT for lung SABR, dosimetric changes to the target volume due to roll-rotational setup errors could be compensated by translational correction, whereas those to the OARs could not in some cases. ADVANCES IN KNOWLEDGE: Roll-rotational setup errors would increase the dose to OARs despite the translational correction. PMID- 26369833 TI - Novel agents for advanced pancreatic cancer. AB - Pancreatic cancer is relatively insensitive to conventional chemotherapy. Therefore, novel agents targeting dysregulated pathways (MAPK/ERK, EGFR, TGF beta, HEDGEHOG, NOTCH, IGF, PARP, PI3K/AKT, RAS, and Src) are being explored in clinical trials as monotherapy or in combination with cytotoxic chemotherapy. This review summarizes the most recent advances with the targeted therapies in the treatment of patients with advanced pancreatic cancer. PMID- 26369835 TI - Second trimester maternal plasma and amniotic fluid adipokines in women who will develop gestational diabetes mellitus. AB - OBJECTIVE: To study the adipokines concentration and glucose homoeostasis in the early-second trimester of women who will develop gestational diabetes mellitus (GDM). MATERIALS AND METHODS: Maternal plasma and fetal amniotic fluid samples were prospectively collected between 2006 and 2007 at the time of mid-trimester amniocentesis. Eight patients found to be affected by GDM were compared with 10 control patients with a normal pregnancy course. Adipokines leptin and adiponectin, as well as insulin and glucose concentration both in amniotic fluid and maternal plasma were compared between cases and controls. HOMA-IR (homeostatic model assessment for insulin resistance) was also calculated both for amniotic fluid and maternal serum. RESULTS: The amniotic fluid adiponectin concentration was higher in women who would develop GDM than in controls (29.9 ng/ml, 95% CI 26.7-49.8 ng/ml, versus 14.9 ng/ml, 95% CI 13.5-18.8 ng/ml), p < 0.05). No difference was shown for leptin both in amniotic fluid and maternal serum. Insulin concentrations in the amniotic fluid were found to be lower in GDM than in controls, while HOMA-IR-index resulted lower in amniotic fluid and higher maternal serum (p < 0.05). CONCLUSIONS: Our data suggests that an earlier alteration in the fetal glucose metabolism will precede the glucose dysmetabolism in pregnancies later complicated by GDM. PMID- 26369837 TI - Complete mitochondrial genome of the giant croaker Nibea japonica (Perciformes, Sciaenidae) and phylogenetic analysis of the Sciaenidae. AB - The giant croaker Nibea japonica (Perciformes, Sciaenidae) is an important economic fish distributing in the East China Sea, South China Sea, and Japan southern coast. In this study, the complete mitochondrial genome of N. japonica was firstly determined. It is 16 496 bp-length and consists of 22 tRNA genes, 13 protein-coding genes, two rRNA genes, and a control region. Except for eight tRNA and ND6 genes, all other mitochondrial genes are encoded on the heavy strand. Phylogenetic analysis revealed that N. japonica, A. amoyensis, and other seven fish first clustered into the Argyrosominae clade. It is consistent with the taxonomic status. Then, the Argyrosominae, Pseudosciaeninae, and Sciaeniae formed the sister group, while the Johniinae became a separate clade, which is inconsistent with the previous phenotypic report. It is suggested that the researches of single gene and taxionomic might lose some significant evolutionary characters. This study will contribute to phyogenetic analysis of the Sciaenidae and the natural resources conservation. PMID- 26369838 TI - Acute pain management in dermatology: mechanisms and pathways. AB - The number of dermatologic surgical procedures performed is increasing each year. The pain associated with these procedures is a major concern for patients and its treatment is part of the increasing emphasis on outcomes and quality of clinical care. Better understanding of pain signaling and how commonly used analgesics function can help improve our surgical pain management. This is part I of a 2 part review that will highlight the anatomy of acute pain signaling from the skin to the central nervous system and the factors that influence the plasticity of the pathway. Having this foundation of knowledge is needed to enhance the clinical treatment of pain. Part II will provide an updated review of available treatments, with an emphasis on their appropriate use for postsurgical pain management. PMID- 26369839 TI - Acute pain management in dermatology: risk assessment and treatment. AB - Dermatologists perform many procedures that require acute pain control with local anesthesia and, in some cases, management of postoperative pain. Identifying early risk factors before a procedure can better prepare both the patient and provider anticipate acute postsurgical pain needs. Taking a multimodal, algorithmic approach to managing acute postsurgical pain in dermatology practice can effectively attenuate acute postsurgical paint and reduce patient opioid requirements. PMID- 26369840 TI - Chronic pain management in dermatology: a guide to assessment and nonopioid pharmacotherapy. AB - Pain is a central component of illness and suffering, yet unfortunately it is frequently undertreated. In dermatology, many acute and chronic conditions are characterized by pain that may require therapeutic intervention in addition to medical treatment aimed at treating the primary disease. To date, however, there are limited recommendations or evidence in the published literature on pain and pain management strategies for patients with skin disease. In an effort to enable providers to more comprehensively and effectively treat chronic pain in the primary and multidisciplinary dermatologic context, these topics will be discussed in this 2-part continuing medical education article. Part I of this series will describe important mechanisms of pain and detail individualized chronic pain assessment and treatment strategies using nonopioid analgesia. PMID- 26369836 TI - Attentional biases to emotional stimuli: Key components of the RDoC constructs of sustained threat and loss. AB - Biased attention to emotional stimuli plays a key role in the RDoC constructs of Sustained Threat and Loss. In this article, we review approaches to assessing these biases, their links with psychopathology, and the underlying neural influences. We then review evidence from twin and candidate gene studies regarding genetic influences on attentional biases. We also discuss the impact of developmental and environmental influences and end with a number of suggestions for future research in this area. PMID- 26369841 TI - Chronic pain management in dermatology: pharmacotherapy and therapeutic monitoring with opioid analgesia. AB - A number of chronic dermatologic conditions may necessitate long-term adjunctive pain management in addition to treatment of the primary skin disease, such as hidradenitis suppurativa, lichen planus, and other systemic diseases associated with significant pain. Adequate management of chronic pain can represent a unique challenge, but remains an integral component of clinical treatment in relevant contexts. For nociceptive pain of moderate to severe intensity, opioid analgesics can be beneficial when other pain management strategies have failed to produce adequate relief. The decision to initiate long-term opioid therapy must be carefully weighed, and individualized treatment plans are often necessary to effectively treat pain while minimizing adverse effects. Part II of this 2-part continuing medical education article will describe the appropriate settings for initiation of opioid analgesia for dermatology patients and detail therapeutic strategies and patient monitoring guidelines. PMID- 26369842 TI - Incidence and risk factors for striae gravidarum. PMID- 26369843 TI - Epidemiology of concomitant psoriasis and hidradenitis suppurativa (HS): experience of a tertiary medical center. PMID- 26369844 TI - Litigation arising from the use of soft-tissue fillers in the United States. PMID- 26369845 TI - Skin self-photography for dysplastic nevus monitoring is associated with a decrease in the number of biopsies at follow-up: a retrospective analytical study. PMID- 26369846 TI - Demographics of women with female pattern hair loss and the effectiveness of spironolactone therapy. PMID- 26369847 TI - Parental leave in dermatology residency: ethical considerations. PMID- 26369848 TI - Beyond JAAD October 2015: articles of interest from the nondermatologic literature. PMID- 26369849 TI - Pulsatile nodule on the ventral wrist. PMID- 26369850 TI - Generalized targetoid eruption in a man with HIV. PMID- 26369851 TI - Three dermoscopic signs of growth of pigmented lesions. PMID- 26369852 TI - Dermoscopy of cutaneous Abrikossoff tumor (granular cell tumor) in a pediatric patient. PMID- 26369853 TI - Exogenous nail pigmentation secondary to pecan nuts (Carya illinoinensis). PMID- 26369854 TI - Temporary ear to cheek suture technique for improved posterior ear surgical access. PMID- 26369855 TI - Nail photography: all 10 fingernails in 1 frame. PMID- 26369856 TI - Reply to: "nail photography- all 10 fingernails in 1 frame". PMID- 26369857 TI - Reply to: "nail photography- all 10 fingernails in 1 frame". PMID- 26369858 TI - Time to move forward after the report of the AAD Task Force for the ABCDEs of Melanoma. PMID- 26369859 TI - Reply to: "time to move forward after the report of the AAD Task Force for the ABCDEs of Melanoma". PMID- 26369860 TI - Is tonsillectomy a therapeutic option for plaque-type psoriasis? PMID- 26369861 TI - Response to: "is tonsillectomy a therapeutic option for plaque-type psoriasis?". PMID- 26369862 TI - Hospitals Known for Nursing Excellence Associated with Better Hospital Experience for Patients. AB - OBJECTIVE: To examine the relationship between Magnet recognition, an indicator of nursing excellence, and patients' experience with their hospitalization reported in the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey. DATA SOURCES: This secondary analysis includes cross-sectional data from the 2010 HCAHPS survey, the American Hospital Association, and the American Nurses Credentialing Center. STUDY DESIGN: We conducted a retrospective observational study. DATA COLLECTION: Using common hospital identifiers, we created a matched set of 212 Magnet hospitals and 212 non-Magnet hospitals. PRINCIPAL FINDINGS: Patients in Magnet hospitals gave their hospitals higher overall ratings, were more likely to recommend their hospital, and reported more positive care experiences with nurse communication. CONCLUSIONS: Magnet recognition is associated with better patient care experiences, which may positively enhance reimbursement for hospitals. PMID- 26369863 TI - Laparoscopic pelvic mesh placement with closure of pelvic floor entrance to prevent small intestine radiation trauma - A retrospective cohort analysis. AB - BACKGROUND: In most pelvic malignancies radiation therapy is a main part of the treatment concept. The main dose limiting organ is the small intestine. Different mechanical methods to prevent radiation damage to the small intestine have been described. We herein report a retrospective study of laparoscopic placement of an absorbable vicryl mesh in patients requiring pelvic radiotherapy displacing the bowel out of the radiation field. PATIENTS/METHODS: The study included 6 consecutive patients requiring definitive radiotherapy due to locally advanced prostate cancer. All patients had small intestine within the radiation fields despite the use of non-invasive displacement methods. RESULTS: All patients underwent laparoscopic small bowel displacement from the pelvis and closure of the pelvic floor entrance using vicryl mesh placement. Peri- or postoperative complications were not seen. Postoperative radiotherapy planning CT scans confirmed displacement of the small intestine allowing all patients to receive the planned radiotherapy volume. CONCLUSION: Laparoscopic mesh placement represents a safe and efficient procedure in patients requiring high-dose pelvic radiation, presenting with unacceptable small intestine volume in the radiation field. As an alternate to native tissue, the vicryl mesh is a safe, effective substitute for small bowel exclusion from external-beam radiation therapy. PMID- 26369864 TI - Undermining and bullying in surgical training: A review and recommendations by the Association of Surgeons in Training. AB - The 2012 General Medical Council National Trainees' Survey found that 13% of UK trainees had experienced undermining or bullying in the workplace. The Association of Surgeons in Training subsequently released a position statement raising concerns stemming from these findings, including potential compromise to patient safety. This article considers the impact of such behaviour on the NHS, and makes recommendations for creating a positive learning environment within the NHS at national, organisational, and local levels. The paper also discusses the nature of issues within the UK, and pathways through which trainees can seek help. PMID- 26369865 TI - Less Than Full-time Training in surgical specialities: Consensus recommendations for flexible training by the Association of Surgeons in Training. AB - Changes in lifestyle, career expectations, and working environments, alongside the feminisation of the workforce have resulted in an increased demand for Less Than Full-time Training (LTFT) within surgery. However, provision of and adequacy of flexible training remain variable. It is important that LTFT options are provided to ensure surgery is an attractive and viable career option, and can compete with other specialties to attract and retain the best candidates to maintain high standards of patient care. LTFT options should be readily available to both genders within surgical specialities. Furthermore, improved information for those considering LTFT should be available, locally, regionally and nationally. Training within LTFT posts should be tailored to the training requirements of the individual, in order to achieve the competencies necessary for completion of training. The recommendations set out in this consensus statement should inform the trainee's position and help guide discussions with respect to the provision of LTFT within surgery. PMID- 26369867 TI - Maternal Body Mass Index Correlates with the Neonatal Physique of Male Infants. AB - Recently, in Japan, the percentage of leanness has risen in young women, and the average birth weight has decreased. An increase in the risk of low birth weight has been reported in lean expectant mothers. In this study, we aimed to clarify the relationship between mother's physique at the beginning of pregnancy and the infant's physique, by focusing on sex differences. The participants were 3,722 mothers who attended health checkups for 18-month-old infants in an urban Japanese city. The participants were limited to those with full-term births, thereby excluding the influence of gestational length. A total of 1,287 mothers, with 621 boys and 666 girls, were analyzed. Public health professionals interviewed the mothers, and transferred the required information from their maternity passbooks. We examined the physical characteristics of the mothers and their infants. Partial correlation analysis, adjusted by gestational length and the mother's age at delivery, was applied to study the association between the mother's BMI and the infant's physique at birth. In the primipara group, only the boys showed significant positive correlation between the mother's BMI and the birth weight (P = 0.025) and the Kaup index (P = 0.035). In the pluripara group, only the boys showed significant positive correlation between the mother's BMI and the head circumference (P = 0.035). Thus, mother's physique may have a stronger influence on the physique of male infants, compared to female infants. The growth-promoting effect of the mother's physique is more apparent in the infants born to the pluripara. PMID- 26369866 TI - Optogenetic stimulation of astrocytes in the posterior hypothalamus increases sleep at night in C57BL/6J mice. AB - A distributed network of neurons regulates wake, non-rapid eye movement (NREM) sleep, and REM sleep. However, there are also glia in the brain, and there is growing evidence that neurons and astroglia communicate intimately to regulate behaviour. To identify the effect of optogenetic stimulation of astrocytes on sleep, the promoter for the astrocyte-specific cytoskeletal protein, glial fibrillary acidic protein (GFAP) was used to direct the expression of channelrhodopsin-2 (ChR2) and the linked reporter gene, enhanced yellow fluorescent protein (EYFP), in astrocytes. rAAV-GFAP-ChR2 (H134R)-EYFP or rAAV GFAP-EYFP was microinjected (750 nL) into the posterior hypothalamus (bilateral) of mice. Three weeks later baseline sleep was recorded (0 Hz) and 24 h later optogenetic stimulation applied during the first 6 h of the lights-off period. Mice with ChR2 were given 5, 10 or 30 Hz stimulation for 6 h (10-ms pulses; 1 mW; 1 min on 4 min off). At least 36 h elapsed between the stimulation periods (5, 10, 30 Hz) and although 0 Hz was always first, the order of the other three stimulation rates was randomised. In mice with ChR2 (n = 7), 10 Hz, but not 5 or 30 Hz stimulation increased both NREM and REM sleep during the 6-h period of stimulation. Delta power did not increase. In control mice (no ChR2; n = 5), 10 Hz stimulation had no effect. This study demonstrates that direct stimulation of astrocytes powerfully induces sleep during the active phase of the sleep-wake cycle and underlines the inclusion of astrocytes in network models of sleep-wake regulation. PMID- 26369868 TI - Anti-idiotypic antibody: A new strategy for the development of a growth hormone receptor antagonist. AB - In general, traditional growth hormone receptor antagonist can be divided into two major classes: growth hormone (GH) analogues and anti-growth hormone receptor (GHR) antibodies. Herein, we tried to explore a new class of growth hormone receptor (GHR) antagonist that may have potential advantages over the traditional antagonists. For this, we developed a monoclonal anti-idiotypic antibody growth hormone, termed CG-86. A series of experiments were conducted to characterize and evaluate this antibody, and the results from a competitive receptor-binding assay, Enzyme Linked Immunosorbent Assays (ELISA) and epitope mapping demonstrate that CG-86 behaved as a typical Ab2beta. Next, we examined its antagonistic activity using in vitro cell models, and the results showed that CG-86 could effectively inhibit growth hormone receptor-mediated signalling and effectively inhibit growth hormone-induced Ba/F3-GHR638 proliferation. In summary, these studies show that an anti-idiotypic antibody (CG-86) has promise as a novel growth hormone receptor antagonist. Furthermore, the current findings also suggest that anti-idiotypic antibody may represent a novel strategy to produce a new class of growth hormone receptor antagonist, and this strategy may be applied with other cytokines or growth factors. PMID- 26369869 TI - Personalized liposome-protein corona in the blood of breast, gastric and pancreatic cancer patients. AB - When nanoparticles (NPs) are dispersed in a biofluid, they are covered by a protein corona the composition of which strongly depends on the protein source. Recent studies demonstrated that the type of disease has a crucial role in the protein composition of the NP corona with relevant implications on personalized medicine. Proteomic variations frequently occur in cancer with the consequence that the bio-identity of NPs in the blood of cancer patients may differ from that acquired after administration to healthy volunteers. In this study we investigated the correlation between alterations of plasma proteins in breast, gastric and pancreatic cancer and the biological identity of clinically approved AmBisome-like liposomes as determined by a combination of dynamic light scattering, zeta potential analysis, one-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis (1D-SDS-PAGE) and semi-quantitative densitometry. While size of liposome-protein complexes was not significantly different between cancer groups, the hard corona from pancreatic cancer patients was significantly less negatively charged. Of note, the hard corona from pancreatic cancer patients was more enriched than those of other cancer types this enrichment being most likely due to IgA and IgG with possible correlations with the autoantibodies productions in cancer. Given the strict relationship between tumor antigen-specific autoantibodies and early cancer detection, our results could be the basis for the development of novel nanoparticle-corona-based screening tests of cancer. PMID- 26369870 TI - Mesenchymal stem cells: In vivo therapeutic application ameliorates carbon tetrachloride induced liver fibrosis in rats. AB - BACKGROUND: Egypt has the highest prevalence of hepatitis C virus in the world with infection rate up to 60%, for which liver fibrosis or hepatic carcinoma is the final outcome. Stem cell therapy provides a new hope for hepatic repair instead of traditional treatment, liver transplantation, as it is safer, gives long term engraftment and avoid expensive immunosuppressive drugs and unexpected hazardous effects. AIM: This work aimed at determining the therapeutic potential of mesenchymal stem cells (MSC) in hepatic repair as a new line of therapy for liver fibrosis. METHODS: 33 female albino rats were divided into three groups: Group I: 10 rats injected subcutaneously with olive oil, Group II: 13 rats injected with carbon tetrachloride (CCl4) and Group III: 10 rats injected with CCl4 then bone marrow derived MSC from male rats. Blood and liver tissue samples were taken from all rats for biochemical and histological study. RESULTS: Liver functions for group II rats showed significant deterioration in response to CCl4 in addition to significant histological changes in liver lobules and portal areas. Those parameters tend to be normal in MSC-treated group. Group III rats revealed normalized liver function and histological picture. Meanwhile, most of the pathological lesions were still detected in rats of second group. CONCLUSION: Undifferentiated MSCs have the ability to ameliorate CCl4 induced liver injury in albino rats in terms of liver functions and histological features. So, stem cell therapy can be considered clinically to offer a hope for patients suffering from liver fibrosis. PMID- 26369871 TI - High-grade Cerebral Arteriovenous Malformation Treated with Targeted Embolization of a Ruptured Site: Wall Enhancement of an Intranidal Aneurysm as a Sign of Ruptured Site. AB - Partial targeted embolization of the ruptured site of cerebral arteriovenous malformations (AVMs) is considered effective to prevent rebleeding. The site of rupture is usually determined by morphological features, such as an intranidal aneurysm or a venous varix; however, the site can be difficult to identify in high-grade AVM with complicated angioarchitecture. The authors present a case of a 36-year-old woman with high-grade AVM presented with repeated hemorrhage. Cerebral angiography showed intranidal aneurysm, which was considered the ruptured site. The T1-weighted imaging with gadolinium enhancement demonstrated linear enhancement along the outer surface of the thickened wall of the intranidal aneurysm, which could be supplementary information to identify the ruptured site. Obliteration of the intranidal aneurysm was successfully achieved by emergent targeted embolization using N-butyl cyanoacrylate. The patient recovered and regained an independent status. The patient underwent volume-staged radiosurgery and experienced no further hemorrhage during the 26 months follow up. Targeted embolization of the ruptured site is considered effective to prevent rebleeding in high-grade cerebral AVMs. Wall enhancement of the intranidal aneurysm, in addition to the structural characteristics, could be helpful in identifying the site of rupture embedded in the complicated angioarchitecture. PMID- 26369872 TI - Specific Shrinkage of Carotid Forks in Moyamoya Disease: A Novel Key Finding for Diagnosis. AB - This study was aimed to analyze the outer diameter of the involved arteries in moyamoya disease, using three-dimensional (3D) constructive interference in steady state (CISS) and direct surgical inspection. Radiological evaluation was performed in 64 patients with moyamoya disease. As the controls, six patients with severe middle cerebral artery (MCA) stenosis and 17 healthy subjects were also recruited. On 3D-CISS, the outer diameter was quantified in the supraclinoid portion of internal carotid artery (C1), the horizontal portions of MCA (M1) and anterior cerebral artery (A1), and basilar artery. The involved carotid fork was directly observed during surgery in another series of three adult patients with moyamoya disease. In 53 adult patients with moyamoya disease, the outer diameters of C1, M1, and A1 segments were 2.3 +/- 0.7 mm, 1.3 +/- 0.5 mm, and 1.0 +/- 0.4 mm in the involved side (n = 91), being significantly smaller than the control (n = 17), severe M1 stenosis (n = 6), and non-involved side in moyamoya disease (n = 15, P < 0.01). There were significant correlations between Suzuki's angiographical stage and the outer diameters of C1, M1, and A1 (P < 0.001). The laterality ratio of C1 and M1 was significantly smaller in unilateral moyamoya disease (n = 20) than the controls and severe MCA stenosis (P < 0.01). Direct observations revealed a marked decrease in the outer diameter of the carotid fork (n = 3). These findings strongly suggest specific shrinkage of the involved arteries in moyamoya disease, which may provide essential information to distinguish moyamoya disease from other intracranial arterial stenosis and shed light on the etiology and novel diagnosis cue of moyamoya disease. PMID- 26369873 TI - Significance of Cerebral Blood Flow Analysis in the Acute Stage after Revascularization Surgery for Moyamoya Disease. AB - Moyamoya disease is a chronic, occlusive cerebrovascular disease with unknown etiology characterized by steno-occlusive changes at the terminal portion of the internal carotid artery, either bilaterally or unilaterally, and an abnormal vascular network at the base of the brain. Surgical revascularization such as extracranial-intracranial (EC-IC) bypass is the preferred procedure for moyamoya disease. Despite the favorable long-term outcome, cerebral infarction and hyperperfusion syndrome are potential complications of this procedure, which can lead to neurological deterioration in the acute stage. In light of the similar clinical presentations between perioperative ischemia and hyperperfusion, it is essential to attempt a prompt cerebral blood flow (CBF) measurement in the acute stage after EC-IC bypass for moyamoya disease to differentiate these distinct pathologies, because the management of cerebral ischemia and hyperperfusion is contradictory to each other. Routine CBF analysis by single-photon emission computed tomography and/or magnetic resonance imaging not only facilitated a safer perioperative management but also provided important information about dynamic pathology of the hemodynamic conversion in the acute stage after revascularization surgery for moyamoya disease. We represent the current status of CBF analysis during the perioperative period of revascularization surgery for moyamoya disease, and sought to discuss its significance and efficacy to avoid surgical complications. PMID- 26369874 TI - The Significance of Cerebral Hemodynamics Imaging in Carotid Endarterectomy: A Brief Review. AB - The indication of carotid endarterectomy (CEA) is principally determined by the presence or absence of symptoms and the degree of stenosis. However, the results of recent studies have implicated the usefulness of cerebral hemodynamics imaging for perioperative assessments. Many studies using single-photon emission computed tomography (SPECT) have demonstrated that cerebral hemodynamics imaging assessments are useful in the prediction and assessment of post-CEA hyperperfusion. In studies using transcranial Doppler ultrasonography, SPECT, or positron-emission tomography (PET), cerebral hemodynamic impairment is highly likely to increase the risk of cerebral infarction in patients with asymptomatic carotid artery stenosis. In other studies using the same modalities, cerebral hemodynamic impairment might be related to cognitive impairment in carotid artery stenosis, and this cognitive impairment might be improved with CEA. Nuclear medicine techniques involve the injection of radioactive tracers. Arterial spin labeling (ASL) is an emerging technique of perfusion magnetic resonance imaging (MRI) for the noninvasive measurement of cerebral perfusion. ASL could detect pathologic states such as hypoperfusion, impaired vasoreactivity, and postoperative hyperperfusion activities that are equivalent to SPECT. In addition, regional perfusion imaging visualizes cerebral perfusion territories by selective ASL. In conclusion, cerebral hemodynamic imaging would be useful for the perioperative assessment of CEA. However, there is a lack of sufficient scientific evidence to confirm the benefits, necessitating further study. PMID- 26369875 TI - Evaluation of Cerebral Perfusion in Patients Undergoing Intravenous Recombinant Tissue Plasminogen Activator Thrombolysis. AB - Currently, the indication for thrombolytic therapy using intravenous recombinant tissue plasminogen activator (rt-PA) is restricted strictly to patients with acute ischemic stroke within 4.5 h of onset. The effect of rt-PA declines over time; therefore, we need to minimize the time delay while generating imaging information. The use of cerebral blood flow imaging is not recommended within this time window. Conversely, the balance of efficacy and the risk of bleeding complications differ among patients > 4.5 h after onset. Several ongoing studies are using mismatch concepts to extend the therapeutic time window for rt-PA. Long awaited reliable software, such as RAPID and PMA, are now available to analyze computed tomography/magnetic resonance perfusion data. Patients with wake-up stroke (WUS) are another group that can be used to expand rt-PA candidates. Diffusion fluid-attenuated inversion recovery mismatch is a promising imaging surrogate to select good candidates with WUS. These trials will cause a therapeutic paradigm shift from time-based to tissue-based strategies in the near future. PMID- 26369876 TI - Elevated Release of Beta-thromboglobulin and Platelet Factor 4 in Cerebral Infarction Patients with Branch Atheromatous Disease: A Preliminary Report. AB - This study evaluated the levels of the platelet activation markers beta thromboglobulin (beta-TG) and platelet factor 4 (PF4) in patients with branch atheromatous disease (BAD). Patients with newly diagnosed cerebral infarctions were recruited into the study; those with cardiogenic cerebral infarctions were excluded. Beta-TG and PF4 levels were measured before therapeutic intervention and compared between patients with and without BAD; Welch's t-test was used to determine significant differences between the groups. A total of 15 subjects were enrolled in the study, and 8 were diagnosed with BAD. Beta-TG (P = 0.031) and PF4 (P = 0.041) levels were significantly higher in the BAD patients than in the non BAD patients. Platelet activity is normally elevated in patients with cerebral infarctions, but is elevated to an even greater extent in BAD patients. The evaluation of beta-TG and PF4 levels may be beneficial for the elucidation of BAD. PMID- 26369877 TI - 3D-FIESTA Magnetic Resonance Angiography Fusion Imaging of Distal Segment of Occluded Middle Cerebral Artery. AB - Middle cerebral artery (MCA) occlusion was examined with basi-parallel anatomical scanning (BPAS) using three-dimensional fast imaging employing steady-state acquisition (3D-FIESTA), and 3D-FIESTA and magnetic resonance angiography (MRA) fusion images were created. We expected that an incidence of hemorrhagic complications due to vessel perforations would be decreased by obtaining vascular information beyond the occlusion and thus acute endovascular revascularization could be performed using such techniques. We performed revascularization for acute MCA occlusion for five patients who were admitted in our hospital from October 2012 to October 2014. Patients consisted of 1 man and 4 women with a mean age of 76.2 years (range: 59-86 years). Fusion images were created from three dimensional time of flight (3D-TOF) MRA and 3D-FIESTA with phase cycling (3D FIESTA-C). Then thrombectomy was performed in all the 5 patients. Merci retriever to 1 patient, Penumbra system to 1, urokinase infusion to 2, and Solitaire to 1 using such techniques. In all cases, a 3D-FIESTA-MRA fusion imaging could depict approximately clear vascular information to at least the M3 segment beyond the occlusion. And each acute revascularization was able to perform smoothly using these imaging techniques. In all cases, there was no symptomatic hemorrhagic complication. It showed that 3D-FIESTA MRA fusion imaging technique could obtain vascular information beyond the MCA occlusion. In this study, no symptomatic hemorrhagic complications were detected. It could imply that such techniques were useful not only to improve treatment efficiency but also to reduce the risk of development of hemorrhagic complications caused by vessel perforations in acute revascularization. PMID- 26369879 TI - Prostaglandin E2 EP2 activation reduces memory decline in R6/1 mouse model of Huntington's disease by the induction of BDNF-dependent synaptic plasticity. AB - Huntington's disease (HD) patients and mouse models show learning and memory impairment even before the onset of motor symptoms. Deficits in hippocampal synaptic plasticity have been involved in the HD memory impairment. Several studies show that prostaglandin E2 (PGE2) EP2 receptor stimulates synaptic plasticity and memory formation. However, this role was not explored in neurodegenerative diseases. Here, we investigated the capacity of PGE2 EP2 receptor to promote synaptic plasticity and memory improvements in a model of HD, the R6/1 mice, by administration of the agonist misoprostol. We found that misoprostol increases dendritic branching in cultured hippocampal neurons in a brain-derived neurotrophic factor (BDNF)-dependent manner. Then, we implanted an osmotic mini-pump system to chronically administrate misoprostol to R6/1 mice from 14 to 18weeks of age. We observed that misoprostol treatment ameliorates the R6/1 long-term memory deficits as analyzed by the T-maze spontaneous alternation task and the novel object recognition test. Importantly, administration of misoprostol promoted the expression of hippocampal BDNF. Moreover, the treatment with misoprostol in R6/1 mice blocked the reduction in the number of PSD-95 and VGluT-1 positive particles observed in hippocampus of vehicle-R6/1 mice. In addition, we observed an increase of cAMP levels in the dentate ' of WT and R6/1 mice treated with misoprostol. Accordingly, we showed a reduction in the number of mutant huntingtin nuclear inclusions in the dentate gyrus of R6/1 mice. Altogether, these results suggest a putative therapeutic effect of PGE2 EP2 receptor in reducing cognitive deficits in HD. PMID- 26369880 TI - Preferences for Early Intervention Mental Health Services: A Discrete-Choice Conjoint Experiment. AB - OBJECTIVE: Early intervention services (EISs) for mental illness may improve outcomes, although treatment engagement is often a problem. Incorporating patients' preferences in the design of interventions improves engagement. A discrete-choice conjoint experiment was conducted in Canada to identify EIS attributes that encourage treatment initiation. METHODS: Sixteen four-level attributes were formalized into a conjoint survey, completed by patients, family members, and mental health professionals (N=562). Participants were asked which EIS option people with mental illness would contact. Latent-class analysis identified respondent classes characterized by shared preferences. Randomized first-choice simulations predicted which hypothetical options, based on attributes, would result in maximum utilization. RESULTS: Participants in the conventional-service class (N=241, 43%) predicted that individuals would contact traditional services (for example, hospital location and staffed by psychologists or psychiatrists). Membership was associated with being a patient or family member and being male. Participants in the convenient-service class (N=321, 57%) predicted that people would contact services promoting easy access (for example, self-referral and access from home). Membership was associated with being a professional. Both classes predicted that people would contact services that included short wait times, direct contact with professionals, patient autonomy, and psychological treatment information. The convenient-service class predicted that people would use an e-health model, whereas the conventional-service class predicted that people would use a primary care or clinic-hospital model. CONCLUSIONS: Provision of a range of services may maximize EIS use. Professionals may be more apt to adopt EISs in line with their beliefs regarding patient preferences. Considering several perspectives is important for service design. PMID- 26369878 TI - Dietary DHA supplementation in an APP/PS1 transgenic rat model of AD reduces behavioral and Abeta pathology and modulates Abeta oligomerization. AB - Increased dietary consumption of docosahexaenoic acid (DHA) is associated with decreased risk for Alzheimer's disease (AD). These effects have been postulated to arise from DHA's pleiotropic effects on AD pathophysiology, including its effects on beta-amyloid (Abeta) production, aggregation, and toxicity. While in vitro studies suggest that DHA may inhibit and reverse the formation of toxic Abeta oligomers, it remains uncertain whether these mechanisms operate in vivo at the physiological concentrations of DHA attainable through dietary supplementation. We sought to clarify the effects of dietary DHA supplementation on Abeta indices in a transgenic APP/PS1 rat model of AD. Animals maintained on a DHA-supplemented diet exhibited reductions in hippocampal Abeta plaque density and modest improvements on behavioral testing relative to those maintained on a DHA-depleted diet. However, DHA supplementation also increased overall soluble Abeta oligomer levels in the hippocampus. Further quantification of specific conformational populations of Abeta oligomers indicated that DHA supplementation increased fibrillar (i.e. putatively less toxic) Abeta oligomers and decreased prefibrillar (i.e. putatively more toxic) Abeta oligomers. These results provide in vivo evidence suggesting that DHA can modulate Abeta aggregation by stabilizing soluble fibrillar Abeta oligomers and thus reduce the formation of both Abeta plaques and prefibrillar Abeta oligomers. However, since fibrillar Abeta oligomers still retain inherent neurotoxicity, DHA may need to be combined with other interventions that can additionally reduce fibrillar Abeta oligomer levels for more effective prevention of AD in clinical settings. PMID- 26369881 TI - Characteristics of U.S. Mental Health Facilities That Offer Suicide Prevention Services. AB - OBJECTIVE: This study characterized mental health facilities that offer suicide prevention services or outcome follow-up after discharge. METHODS: The study analyzed data from 8,459 U.S. mental health facilities that participated in the 2010 National Mental Health Services Survey. Logistic regression analyses were used to compare facilities that offered neither of the prevention services with those that offered both or either service. RESULTS: About one-fifth of mental health facilities reported offering neither suicide prevention services nor outcome follow-up. Approximately one-third offered both, 25% offered suicide prevention services only, and 21% offered only outcome follow-up after discharge. Facilities that offered neither service were less likely than facilities that offered either to offer comprehensive support services or special programs for veterans; to offer substance abuse services; and to be accredited, licensed, or certified. CONCLUSIONS: Further examination of facilitators and barriers in implementing suicide prevention services in mental health facilities is warranted. PMID- 26369882 TI - Further Validation of the Pathways Housing First Fidelity Scale. AB - OBJECTIVE: This study examined whether Housing First fidelity ratings correspond to program operation descriptions from administrative data and predict client outcomes. METHODS: A multisite, randomized controlled trial (At Home/Chez Soi) in five Canadian cities included two assessments of 12 programs over two years. Outcomes for 1,158 clients were measured every six months. Associations between fidelity ratings and administrative data (Spearman correlations) and participant outcomes (mixed-effects modeling) were examined. RESULTS: Fidelity ratings were generally good (mean +/- SD=136.6 +/- 10.3 out of a possible range of 38-152; 87% of maximum value). Fidelity was significantly associated with three of four measures of program operation, with correlations between .55 and .60. Greater program fidelity was associated with improvement in housing stability, community functioning, and quality of life. CONCLUSIONS: Variation in program fidelity was associated with operations and outcomes, supporting scale validity and intervention effectiveness. These findings reinforced the value of using fidelity monitoring to conduct quality assurance and technical assistance activities. PMID- 26369883 TI - Predictors of Treatment Noncompletion in a Sample of Inpatient Sex Offenders With Serious Mental Illness. AB - OBJECTIVE: Very little is known regarding noncompletion of sex offender treatment among sex offenders with serious psychiatric illness. The purpose of the study was to identify factors predictive of treatment noncompletion in a forensic psychiatric sample of 156 adult male sex offenders. METHODS: All data were coded from archival client medical records. Variables of interest, including indicators of historical risk and clinical diagnoses made by hospital psychiatrists, were entered into both a linear regression equation with percentage of groups attended over two years as a continuous variable and a logistic regression equation for predicting more or less than 50% sex offender treatment group attendance. RESULTS: Significant predictors of treatment noncompletion included number of arrests, recent physical aggression, length of admission, and diagnoses of borderline personality disorder, psychosis, and intellectual impairments. CONCLUSIONS: The resulting predictors indicate a combination of relevant variables for psychiatric sex offenders, combining both criminal risk and clinical risk indicators. Suggested reasons for these findings and implications for predicting treatment noncompletion by psychiatric sex offenders are discussed. PMID- 26369884 TI - Augmenting Ongoing Depression Care With a Mutual Peer Support Intervention Versus Self-Help Materials Alone: A Randomized Trial. AB - OBJECTIVE: Various models of peer support may be implemented in mental health settings. This randomized trial assessed the effectiveness of a telephone delivered mutual peer support intervention. METHODS: A total of 443 patients receiving ongoing depression treatment from the U.S. Department of Veterans Affairs were enrolled in either enhanced usual care (N=243) or the peer support intervention (N=200). Intent-to-treat analyses assessed outcomes at six months postenrollment, excluding 56 patients who experienced an unplanned telephone platform shutdown. RESULTS: At baseline, patients had substantial depressive symptoms, functional limitations, and low quality of life. Both groups showed significant clinical improvements at six months, with no significant differences by group. CONCLUSIONS: Telephone-delivered mutual peer support for patients with depression did not improve outcomes beyond those observed with enhanced usual care. Other peer support models, with more "professionalized" peers delivering a structured curriculum, may be more effective. PMID- 26369885 TI - American Christian Engagement With Mental Health and Mental Illness. AB - Although religious belief and practice are relevant to mental health outcomes, many clinicians lack knowledge of particular religious traditions required to make informed judgments about referral to and collaboration with faith-based organizations and clinicians. This Open Forum examines five diverse American Christian approaches to mental health and mental illness-pastoral care and counseling, biblical counseling, integrationism, Christian psychology, and the work of the Institute for the Psychological Sciences--that are relevant for contemporary mental health service delivery. Each of these movements is briefly described and placed in historical, conceptual, and organizational context. Knowledge of the diverse and varied terrain of American Christian engagement with mental health care can inform clinicians' interactions with faith-based providers, clarify opportunities for responsible collaboration, and provide important insight into religious subcultures with faith-based concerns about contemporary psychiatric care. PMID- 26369886 TI - Health Plans' Early Response to Federal Parity Legislation for Mental Health and Addiction Services. AB - OBJECTIVE: In 2008, the federal Mental Health Parity and Addiction Equity Act (MHPAEA) passed, prohibiting U.S. health plans from subjecting mental health and substance use disorder (behavioral health) coverage to more restrictive limitations than those applied to general medical care. This require d some health plans to make changes in coverage and management of services. The aim of this study was to examine private health plans' early responses to MHPAEA (after its 2010 implementation), in terms of both intended and unintended effects. METHODS: Data were from a nationally representative survey of commercial health plans regarding the 2010 benefit year and the preparity 2009 benefit year (weighted N=8,431 products; 89% response rate). RESULTS: Annual limits specific to behavioral health care were virtually eliminated between 2009 and 2010. Prevalence of behavioral health coverage was unchanged, and copayments for both behavioral and general medical services increased slightly. Prior authorization requirements for specialty medical and behavioral health outpatient services continued to decline, and the proportion of products reporting strict continuing review requirements increased slightly. Contrary to expectations, plans did not make significant changes in contracting arrangements for behavioral health services, and 80% reported an increase in size of their behavioral health provider network. CONCLUSIONS: The law had the intended effect of eliminating quantitative limitations that applied only to behavioral health care without unintended consequences such as eliminating behavioral health coverage. Plan decisions may also reflect other factors, including anticipation of the 2010 regulations and a continuation of trends away from requiring prior authorization. PMID- 26369887 TI - The relationship between fatigue and participation in spinal cord injury. AB - STUDY DESIGN: Cross-sectional national survey. OBJECTIVES: To explore the association between fatigue and community participation frequency and provide an adjusted model of the relationship including important covariates. SETTING: Canada; Community. METHODS: Data were obtained from the Rick Hansen Spinal Cord Injury Registry Community Survey. We used multi-variable regression analyses with hierarchical backward elimination, including variable specification, interaction assessment and confounding assessment. Variables with statistically significant correlation with the primary-dependent variable (participation) were included for modeling. RESULTS: The crude model of association between fatigue and participation accounted for 7.2% of the variance in participation scores. The full model with all a priori selected variables accounted for 25.1% of variance in participation scores. The adjusted model, including the identified confounders (pain, depressive mood, comorbidities and level of injury), accounted for 21.1% of variance in participation scores. Depressive mood variables had the highest standardized beta coefficients, reflecting the largest contribution to this model. CONCLUSION: Fatigue has a statistically significant negative association with participation for individuals with spinal cord injury, when controlling for pain, depressive mood, comorbidities and level of injury. Multifaceted clinical interventions and research addressing fatigue, pain and depressive symptoms are warranted. PMID- 26369888 TI - A comparison of high vs standard tidal volumes in ventilator weaning for individuals with sub-acute spinal cord injuries: a site-specific randomized clinical trial. AB - STUDY DESIGN: Prospective, randomized, controlled parallel group trial with single-blinded data analysis. OBJECTIVES: To determine the safety and efficacy of higher (20 ml kg(-1) ideal body weight (IBW)) vs standard (10 ml kg(-1) IBW) tidal volumes (Vt) for patients with sub-acute traumatic tetraplegia during ventilator weaning using a 14-day (minimum) weaning protocol. SETTING: United States regional spinal cord injury treatment center. METHODS: Thirty-three ventilator requiring inpatients were randomized to either the higher (Group 1) or the standard (Group 2) Vt protocol. Initially, all patients were ventilated at 10 ml kg(-1) IBW Vt and 5 cm H(2)O [corrected] of PEEP for 72 h. For Group 1, Vt was raised 100 ml kg(-1) until reaching target Vt of 20 ml kg(-1) IBW. Group 2 was maintained at Vt of 10 ml kg(-1) IBW. Plateau pressures were kept at or below 30 cm H(2)O. [corrected]. Safety outcomes included incidence of adverse events. RESULTS: Because of smaller than expected enrollment, evaluation of efficacy was not possible. Therefore, we report the safety outcomes of 33 study participants. The 16 patients in Group 1 and 17 patients in Group 2 were demographically similar at baseline, except for age. The average age was 39.3 years in Group 1 and 27.2 years in Group 2, (P=0.002). There was no difference in median days to wean: 14.5 days in Group 1 and 14 days in Group 2. The incidence of adverse pulmonary events was similar between groups. CONCLUSION: Higher tidal volumes can be safely utilized during weaning of patients with tetraplegia from mechanical ventilation using a 14-day weaning protocol. PMID- 26369889 TI - Text input speed in persons with cervical spinal cord injury. AB - STUDY DESIGN: This is a prospective clinical study. OBJECTIVES: The objectives of this study were to determine text input speed (TIS) in persons with cervical spinal cord injury (SCI) and to study the influence of personal characteristics and type of computer access device on TIS. SETTING: This study was conducted in the Rehabilitation Department, Garches, France. METHODS: People with cervical SCI were included if their level of injury was between C4 and C8 Asia A or B, and if they were computer users. In addition, able-bodied people were recruited from the hospital staff. Each participant underwent a single evaluation using their usual computer access devices. TIS was evaluated during a 10- min copying task. The relationship between the characteristics of participants with cervical SCI, type of computer access device and TIS were analyzed using a Scheirer-Ray-Hare test (nonparametric test similar to a two-way analysis of variance). RESULTS: Thirty five participants with cervical SCI and 21 able-bodied people were included. Median TIS of participants with cervical SCI was 11 (6; 14) words per minute (w.p.m.) and of able-bodied participants was 19 (14; 24) w.p.m. (P=0.001). Median TIS of participants with lesions at or above C5 was 12 (4; 13) w.p.m. and of those with lesionsbelow C5 was 10 (9; 18) w.p.m. (P=0.38) [corrected].The Scheirer-Ray-Hare test showed that only the type of computer access device significantly influenced TIS. Surprisingly, none of the person's characteristics, including the level of cervical lesion, affected TIS. CONCLUSION: This is the first study to analyze TIS in a group of participants with cervical SCI. The results showed that only the type of computer access device influenced TIS. PMID- 26369891 TI - Bis(mandelato)borate: an effective, inexpensive spiroborate anion for chiral resolution. AB - Bis(mandelato)borate [B(Man)2](-) (R- or S-) anions are simply prepared and appear widely effective for resolution of racemic cations. Three examples demonstrate their scope; the alkaloid tetrahydropalmatine (THP), 1,2 diaminopropane (1,2-dap) and the metal-organic complex [Co(phen)3](3+) are readily resolved, either by a facile one-pot procedure, or via counter-ion metathesis. PMID- 26369890 TI - Observational study of the effectiveness of spinal cord injury rehabilitation using the Spinal Cord Injury-Ability Realization Measurement Index. AB - STUDY DESIGN: Retrospective observational study. OBJECTIVES: The objective of this study was to determine the rehabilitation potential and the extent to which it is realized in a cohort of spinal cord injury patients using the Spinal Cord Injury-Ability Realization Measurement Index (SCI-ARMI) and to study the clinical factors that influence this realization. SETTING: Two spinal units in Italy. METHODS: Consecutive patients were assessed at the end of an in-patient rehabilitation program using the Spinal Cord Independence Measure and the International Standards for Neurological Classification of Spinal Cord Injury. On the basis of these data and of the age and gender of the patients, we calculated the SCI-ARMI score. Regression analyses were performed to study the relationship between clinical factors and the extent to which rehabilitation potential is realized. RESULTS: We examined the data for 306 patients. Most patients were discharged without having reached their rehabilitation potential, with an SCI ARMI score <80%. SCI-ARMI scores at discharge were positively influenced by etiology and the lesion level and correlated negatively with lesion severity and the presence of complications during rehabilitation. CONCLUSION: The SCI-ARMI is an effective tool that can be used to measure the achievement of rehabilitation potential in SCI patients and to identify groups of patients who are at risk of not meeting their rehabilitative potential. PMID- 26369892 TI - Morphology and local conductance of single crystalline Bi2Te3 thin films on mica. AB - The relation between surface morphology and local conductance was studied for single crystalline thin films of Bi2Te3 grown on mica. Atomic force microscopy and electron diffraction revealed the hexagonal order of the surface with quintuple layer steps and spiral islands. Furthermore, the experiments using contact mode AFM with conducting tip performed at room temperature revealed the high conductance of the surface, which was locally reduced due to changes in the local electronic structure at the defects (e.g. edges of the terraces). Contact current-voltage characteristics tested over the surface showed a linear behavior in every point, with the resistance significantly lower than the resistance of reference metallic samples (gold, platinum). We show that local conductivity AFM is a good technique to exploit the peculiar surface properties of topological insulators. PMID- 26369893 TI - SQUIRE 2.0 (Standards for QUality Improvement Reporting Excellence): revised publication guidelines from a detailed consensus process. AB - Since the publication of Standards for QUality Improvement Reporting Excellence (SQUIRE 1.0) guidelines in 2008, the science of the field has advanced considerably. In this manuscript, we describe the development of SQUIRE 2.0 and its key components. We undertook the revision between 2012 and 2015 using (1) semistructured interviews and focus groups to evaluate SQUIRE 1.0 plus feedback from an international steering group, (2) two face-to-face consensus meetings to develop interim drafts and (3) pilot testing with authors and a public comment period. SQUIRE 2.0 emphasises the reporting of three key components of systematic efforts to improve the quality, value and safety of healthcare: the use of formal and informal theory in planning, implementing and evaluating improvement work; the context in which the work is done and the study of the intervention(s). SQUIRE 2.0 is intended for reporting the range of methods used to improve healthcare, recognising that they can be complex and multidimensional. It provides common ground to share these discoveries in the scholarly literature (http://www.squire-statement.org). PMID- 26369894 TI - Measuring and improving patient safety through health information technology: The Health IT Safety Framework. AB - Health information technology (health IT) has potential to improve patient safety but its implementation and use has led to unintended consequences and new safety concerns. A key challenge to improving safety in health IT-enabled healthcare systems is to develop valid, feasible strategies to measure safety concerns at the intersection of health IT and patient safety. In response to the fundamental conceptual and methodological gaps related to both defining and measuring health IT-related patient safety, we propose a new framework, the Health IT Safety (HITS) measurement framework, to provide a conceptual foundation for health IT related patient safety measurement, monitoring, and improvement. The HITS framework follows both Continuous Quality Improvement (CQI) and sociotechnical approaches and calls for new measures and measurement activities to address safety concerns in three related domains: 1) concerns that are unique and specific to technology (e.g., to address unsafe health IT related to unavailable or malfunctioning hardware or software); 2) concerns created by the failure to use health IT appropriately or by misuse of health IT (e.g. to reduce nuisance alerts in the electronic health record (EHR)), and 3) the use of health IT to monitor risks, health care processes and outcomes and identify potential safety concerns before they can harm patients (e.g. use EHR-based algorithms to identify patients at risk for medication errors or care delays). The framework proposes to integrate both retrospective and prospective measurement of HIT safety with an organization's existing clinical risk management and safety programs. It aims to facilitate organizational learning, comprehensive 360 degree assessment of HIT safety that includes vendor involvement, refinement of measurement tools and strategies, and shared responsibility to identify problems and implement solutions. A long term framework goal is to enable rigorous measurement that helps achieve the safety benefits of health IT in real-world clinical settings. PMID- 26369895 TI - Direct exfoliation and dispersion of two-dimensional materials in pure water via temperature control. AB - The high-volume synthesis of two-dimensional (2D) materials in the form of platelets is desirable for various applications. While water is considered an ideal dispersion medium, due to its abundance and low cost, the hydrophobicity of platelet surfaces has prohibited its widespread use. Here we exfoliate 2D materials directly in pure water without using any chemicals or surfactants. In order to exfoliate and disperse the materials in water, we elevate the temperature of the sonication bath, and introduce energy via the dissipation of sonic waves. Storage stability greater than one month is achieved through the maintenance of high temperatures, and through atomic and molecular level simulations, we further discover that good solubility in water is maintained due to the presence of platelet surface charges as a result of edge functionalization or intrinsic polarity. Finally, we demonstrate inkjet printing on hard and flexible substrates as a potential application of water-dispersed 2D materials. PMID- 26369896 TI - Synthesis, crystal structure and magnetic properties of H2tppz[ReCl6] and [Cu(bpzm)2(MU-Cl)ReCl3(MU-ox)Cu(bpzm)2(MU-ox)ReCl3(MU-Cl)]n. AB - Two new Re(iv) compounds of formulae H2tppz[ReCl6] (1) and [Cu(bpzm)2(MU Cl)ReCl3(MU-ox)Cu(bpzm)2(MU-ox)ReCl3(MU-Cl)]n (2) [tppz = 2,3,5,6-tetrakis(2 pyridyl)pyrazine and bpzm = bis(pyrazolyl-1-yl)methane] have been prepared and their crystal structures determined by X-ray diffraction on single crystals. Compound 1 is a mononuclear species whose structure consists of octahedral hexachlororhenate(iv) anions and diprotonated H2tppz(2+) cations which are arranged in the unit cell as alternating anionic and cationic layers, held together by electrostatic forces. The structure of 2 is made up of alternating [Cu(1)(bpzm)2](2+) and [(ox)ReCl3(MU-Cl)Cu(2)(bpzm)2(MU-Cl)ReCl3(ox)](2-) entities interlinked by oxalate bridges to afford a neutral heterobimetallic chain. The oxalate group adopts the didentate (at Re)/monodentate (at Cu) bridging mode. The magnetic behavior of 1 and 2 has been investigated over the temperature range 1.9-295 K. 1 is a magnetically diluted Re(iv) complex, the relatively large value of the zero-field splitting of the ground level [D = 15.8(2) cm(-1)] accounting for the variation of chiMT in the low temperature range. Weak intrachain ferromagnetic interactions between Re(iv) and Cu(ii) through oxalate (J1 = +0.15 cm(-1)) and single chloro (J2 = +4.9 cm(-1)) bridges occur in 2 which are obscured by the large zero-field splitting of the Re(iv) ion (DRe = 42 cm(-1)). In addition, interchain antiferromagnetic interactions are also involved in 2 which are responsible for the metamagnetic behavior observed, the value of the critical dc magnetic field (Hc) being 20 kOe. PMID- 26369898 TI - Antineutrophil cytoplasmic antibody negative pauci-immune extracapillary glomerulonephritis. AB - AIM: Pauci-immune extracapillary glomerulonephritis (PEGN) is one of the most common causes of rapidly progressive glomerulonephritis and is usually associated with circulating anti-neutrophil cytoplasmic antibodies (ANCAs). However, a significant number of individuals with PEGN test negative for ANCA and this study aimed to analyze the characteristics of this subgroup of patients. METHODS: Patients from two centres who were diagnosed with PEGN between 1997 and 2014 were studied retrospectively. Clinicopathological characteristics and renal outcome were compared between patients presenting with pauci-immune necrotizing extracapillary glomerulonephritis associated or not with the presence of circulating ANCA. RESULTS: Among the 114 patients with PEGN, 29 (25.4%) were ANCA negative. Compared with the 85 ANCA-positive patients, ANCA-negative patients were younger at the onset (54.8 +/- 17.2 vs. 62 +/- 14.0 years; P < 0.05). The median level of urinary protein excretion was significantly higher among ANCA negative patients (3.1 vs. 1 g/24 h; P < 0.001), whereas no differences were found in renal function and need for dialysis between ANCA-negative and positive groups. Extrarenal involvement was present independently of ANCA status. Histological analysis showed that ANCA-negative patients were more likely to have mesangial proliferation (P < 0.05). Renal and global survival were similar between ANCA-negative and positive patients, and treatment response and relapse rates were comparable in both groups. CONCLUSIONS: ANCA-negative pauci-immune extracapillary glomerulonephritis is not a rare condition and is part of a systemic vasculitis disease. Although ANCA-negative patients have renal and histological characteristics that differ from ANCA-positive patients, renal survival and treatment response in PEGN are independent of ANCA status. PMID- 26369897 TI - Identification of bolting-related microRNAs and their targets reveals complex miRNA-mediated flowering-time regulatory networks in radish (Raphanus sativus L.). AB - MicroRNAs (miRNAs) play vital regulatory roles in plant growth and development. The phase transition from vegetative growth to flowering is crucial in the life cycle of plants. To date, miRNA-mediated flowering regulatory networks remain largely unexplored in radish. In this study, two small RNA libraries from radish leaves at vegetative and reproductive stages were constructed and sequenced by Solexa sequencing. A total of 94 known miRNAs representing 21 conserved and 13 non-conserved miRNA families, and 44 potential novel miRNAs, were identified from the two libraries. In addition, 42 known and 17 novel miRNAs were significantly differentially expressed and identified as bolting-related miRNAs. RT-qPCR analysis revealed that some miRNAs exhibited tissue- or developmental stage specific expression patterns. Moreover, 154 target transcripts were identified for 50 bolting-related miRNAs, which were predominately involved in plant development, signal transduction and transcriptional regulation. Based on the characterization of bolting-related miRNAs and their target genes, a putative schematic model of miRNA-mediated bolting and flowering regulatory network was proposed. These results could provide insights into bolting and flowering regulatory networks in radish, and facilitate dissecting the molecular mechanisms underlying bolting and flowering time regulation in vegetable crops. PMID- 26369899 TI - Bisphosphonates for preventing bone disease in kidney transplant recipients: a meta-analysis of randomized controlled trials. AB - An estimated 60% of kidney transplant recipients have mineral bone disease and about 0.5% break their hip within the first year after transplantation. We conducted a systematic review of benefits and harms of bisphosphonates in kidney transplant recipients. We searched CENTRAL (Issue 5, 2015) for randomized controlled trials in all languages and screened the reference list of an earlier Cochrane review. One reviewer identified the trials, extracted all data, and assessed risk of bias. Meta-analysis used a random effects model, with results expressed as risk ratios (RR) or mean differences (MD) with 95% confidence intervals (CI). Bisphosphonates have uncertain effects on death (RR 0.45, CI 0.04 4.69) and vertebral fractures (RR 0.58, CI 0.24-1.43, I(2) 0%). Bisphosphonates moderately to importantly reduce the loss of vertebral bone mineral density (MD 5.98%, CI 3.77-8.18% change from baseline in g calcium/cm2 at 12 months, I(2) 91%) and femoral bone mineral density (MD 5.57%, 3.12-8.01% change from baseline in g calcium/cm2 at 12 months, I(2) 69%). At this stage, insufficient evidence exists to support routine use of bisphosphonates to reduce fracture risk after kidney transplantation. Data on important health outcomes are lacking, surrogate outcomes poorly reflect bone quality in kidney transplant recipients, and serious adverse events are not studied and reported systematically. PMID- 26369900 TI - The child with vasculitic rash: a 10-year retrospective study. PMID- 26369901 TI - Using a dry electrode EEG device during balance tasks in healthy young-adult males: Test-retest reliability analysis. AB - BACKGROUND: The analysis of brain activity during balance is an important topic in different fields of science. Given that all measurements involve an error that is caused by different agents, like the instrument, the researcher, or the natural human variability, a test-retest reliability evaluation of the electroencephalographic assessment is a needed starting point. However, there is a lack of information about the reliability of electroencephalographic measurements, especially in a new wireless device with dry electrodes. OBJECTIVE: The current study aims to analyze the reliability of electroencephalographic measurements from a wireless device using dry electrodes during two different balance tests. METHOD: Seventeen healthy male volunteers performed two different static balance tasks on a Biodex Balance Platform: (a) with two feet on the platform and (b) with one foot on the platform. Electroencephalographic data was recorded using Enobio (Neuroelectrics). The mean power spectrum of the alpha band of the central and frontal channels was calculated. Relative and absolute indices of reliability were also calculated. RESULTS: In general terms, the intraclass correlation coefficient (ICC) values of all the assessed channels can be classified as excellent (>0.90). The percentage standard error of measurement oscillated from 0.54% to 1.02% and the percentage smallest real difference ranged from 1.50% to 2.82%. CONCLUSION: Electroencephalographic assessment through an Enobio device during balance tasks has an excellent reliability. However, its utility was not demonstrated because responsiveness was not assessed. PMID- 26369902 TI - Fatal tracheal aspergillosis during rituximab combined chemotherapy for diffuse large B-cell lymphoma that developed after lung transplantation. AB - Invasive tracheal aspergillosis (ITA) is an infection that is unique to patients who have undergone lung transplantation (LT). Although the activity of this disease often appears on imaging, we encountered a case of ITA that became exacerbated, despite few computed tomography (CT) findings, during rituximab combined chemotherapy for diffuse large B-cell lymphoma. ITA developed during immunosuppressive therapy after LT. Because CT findings may show false-negative results, bronchoscopy is recommended for such cases. PMID- 26369903 TI - Structural features affecting the enzymatic digestibility of pine wood pretreated with ionic liquids. AB - Pretreating lignocellulosic biomass with certain ionic liquids results in structural and chemical changes that make the biomass more digestible by enzymes. In this study, pine wood was pretreated with 1-ethyl-3-methylimidazolium chloride/acetate ([C2 mim]Cl and [C2 mim][OAc]) at different temperatures to investigate the relative importance of substrate features, such as accessible surface area, cellulose crystallinity, and lignin content, on enzymatic digestibility. The ionic liquid pretreatments resulted in glucan conversions ranging from 23% to 84% on saccharification of the substrates, with [C2 mim][OAc] being more effective than [C2 mim]Cl. The pretreatments resulted in no delignification of the wood, some loss of cellulose crystallinity under certain conditions, and varying levels of increased surface area. Enzymatic digestibility closely correlated with accessible surface area and porosity measurements obtained using Simons' staining and thermoporosimetry techniques. Increased accessible surface area was identified as the principal structural feature responsible for the improved enzymatic digestibility. PMID- 26369904 TI - Assessing variability in chemical acute toxicity of unionid mussels: Influence of intra- and interlaboratory testing, life stage, and species. AB - The authors developed a toxicity database for unionid mussels to examine the extent of intra- and interlaboratory variability in acute toxicity tests with mussel larvae (glochidia) and juveniles; the extent of differential sensitivity of the 2 life stages; and the variation in sensitivity among commonly tested mussels (Lampsilis siliquoidea, Utterbackia imbecillis, and Villosa iris), commonly tested cladocerans (Daphnia magna and Ceriodaphnia dubia), and fish (Oncorhynchus mykiss, Pimephales promelas, and Lepomis macrochirus). The results of these analyses indicate that intralaboratory variability for median effect concentrations (EC50) averaged about 2-fold for both life stages, whereas interlaboratory variability averaged 3.6-fold for juvenile mussels and 6.3-fold for glochidia. The EC50s for juveniles and glochidia were within a factor of 2 of each other for 50% of paired records across chemicals, with juveniles more sensitive than glochidia by more than 2-fold for 33% of the comparisons made between life stages. There was a high concurrence of sensitivity of commonly tested L. siliquoidea, U. imbecillis, and V. iris to that of other mussels. However, this concurrence decreased as the taxonomic distance of the commonly tested cladocerans and fish to mussels increased. The compiled mussel database and determination of data variability will advance risk assessments by including more robust species sensitivity distributions, interspecies correlation estimates, and availability of taxon-specific empirically derived application factors for risk assessment. PMID- 26369905 TI - Adaptation of the HIV Stigma Scale in Spaniards with HIV. AB - The primary goal of this study was to adapt Berger, Ferrans, & Lahley (2001) HIV Stigma Scale in Spain, using Bunn, Solomon, Miller, & Forehand (2007) version. A second goal assessed whether the four-factor structure of the adapted scale could be explained by two higher-order dimensions, perceived external stigma and internalized stigma. A first qualitative study (N = 40 people with HIV, aged 28 59) was used to adapt the items and test content validity. A second quantitative study analyzed construct and criterion validity. In this study participants were 557 people with HIV, aged 18-76. The adapted HIV Stigma Scale for use in Spain (HSSS) showed a good internal consistency (alpha = .88) and good construct validity. Confirmatory Factor Analyses yielded a first-order, four-factor structure and a higher-order, bidimensional structure with the two expected factors (RMSEA = .051, 90% CI [.046, .056]; RMR = .073; GFI = .96; AGFI = .96; CFI = .98). Negative relations were found between stigma and quality of life (r = -.39; p < .01), self-efficacy to cope with stigma (r = -.50; p < .01) and the degree of HIV status disclosure (r = -.35; p < .01). Moreover, the people who had suffered AIDS-related opportunistic infections had a higher score in the Perceived External Stigma dimension than those who had not suffered them, t (493) = 3.02, p = .003, d = 0.26. PMID- 26369906 TI - Does electromagnetic hypersensitivity originate from nocebo responses? Indications from a qualitative study. AB - Idiopathic Environmental Intolerance attributed to Electromagnetic Fields (IEI EMF) is a condition in which symptoms are attributed to electromagnetic field (EMF) exposure. As electro-hypersensitive (EHS) people have repeatedly been observed, during provocation trials, to report symptoms following perceived rather than actual exposure, the hypothesis has been put forward that IEI-EMF originates from psychological mechanisms, especially nocebo responses. This paper examines this hypothesis, using data from a qualitative study aimed at understanding how EHS people come to regard themselves as such. Forty self diagnosed EHS people were interviewed. A typified model of their attribution process was then elaborated, inductively, from their narratives. This model is linear and composed of seven stages: (1) onset of symptoms; (2) failure to find a solution; (3) discovery of EHS; (4) gathering of information about EHS; (5) implicit appearance of conviction; (6) experimentation; (7) conscious acceptance of conviction. Overall, symptoms appear before subjects start questioning effects of EMF on their health, which is not consistent with the hypothesis that IEI-EMF originates from nocebo responses to perceived EMF exposure. However, such responses might occur at the sixth stage of the process, potentially reinforcing the attribution. It remains possible that some cases of IEI-EMF originate from other psychological mechanisms. PMID- 26369907 TI - Aspergillus fumigatus Cap59-like protein A is involved in alpha1,3-mannosylation of GPI-anchors. AB - Glycosylphosphatidylinositol (GPI) attaches a variety of eukaryotic proteins to the outer leaflet of the plasma membrane. In fungi, these proteins may also be transferred to the cell wall, to which they are covalently linked via a remnant of the GPI-anchor. They play crucial physiological roles in cell-cell interactions, adhesion or cell wall biogenesis. The biosynthesis of GPI-anchors in the endoplasmic reticulum, their transfer to proteins, early remodelling and transport to the Golgi apparatus has been fairly well described. In contrast, almost nothing is known about the genes and enzymes involved in adding glycan side chains to GPI after protein attachment. In this study, we characterized an alpha1,3-mannosyltransferase involved in maturation of GPI-anchors from the pathogenic fungus Aspergillus fumigatus. This enzyme shows homology to Cryptococcus neoformans Cap59p, a putative glycosyltransferase involved in capsule formation and virulence, and was thus named Cap59-like protein A (ClpA). Targeted deletion of the clpA gene in A. fumigatus led to absence of alpha1,3 mannose from mature GPI-anchors. The enzyme was further located to the Golgi-like apparatus of A. fumigatus and was shown to be active in the yeast Saccharomyces cerevisiae. PMID- 26369908 TI - Identification and biological consequences of the O-GlcNAc modification of the human innate immune receptor, Nod2. AB - Nucleotide-binding oligomerization domain 2 (Nod2) is an intracellular receptor that can sense the bacterial peptidoglycan component, muramyl dipeptide. Upon activation, Nod2 induces the production of various inflammatory molecules such as cytokines and chemokines. Genetic linkage analysis identified and revealed three major mutations in Nod2 that are associated with the development of Crohn's disease. The objective of this study is to further characterize this protein by determining whether Nod2 is posttranslationally modified by O-N-acetylglucosamine (O-GlcNAc). O-GlcNAcylation is one type of posttranslational modification in which the O-GlcNAc transferase transfers GlcNAc from UDP-GlcNAc to selected serine and threonine residues of intracellular proteins. We found that wild-type Nod2 and a Nod2 Crohn's-associated variant are O-GlcNAcylated and this modification affects Nod2's ability to signal via the nuclear factor kappa B pathway. PMID- 26369909 TI - Natural variation in the C-repeat binding factor cold response pathway correlates with local adaptation of Arabidopsis ecotypes. AB - The natural range of Arabidopsis thaliana (Arabidopsis) encompasses geographical regions that have greatly differing local climates, including harshness of winter temperatures. A question thus raised is whether differences in freezing tolerance might contribute to local adaptation in Arabidopsis. Consistent with this possibility is that Arabidopsis accessions differ in freezing tolerance and that those collected from colder northern latitudes are generally more tolerant to freezing than those collected from warmer southern latitudes. Moreover, recent studies with Arabidopsis genotypes collected from sites in Sweden (SW) and Italy (IT) have established that the two accessions are locally adapted, that the SW ecotype is more tolerant of freezing than the IT ecotype, and that genetic differences between the two ecotypes that condition local adaptation and freezing tolerance map to a region that includes the C-repeat binding factor (CBF) locus. The CBF locus includes three genes - CBF1, CBF2 and CBF3 - that are induced by low temperature and encode transcription factors that regulate a group of more than 100 genes, the CBF regulon, which impart freezing tolerance. Here we show that cold induction of most CBF regulon genes is lower in IT plants compared with SW plants, and that this is due to the IT CBF2 gene encoding a non-functional CBF2 protein. The non-functional IT CBF2 protein also contributes to the lower freezing tolerance of the IT plants compared with the SW plants. Taken together, studies on the SW and IT ecotypes provide evidence that natural variation in the CBF pathway has contributed to adaptive evolution in these Arabidopsis populations. PMID- 26369910 TI - Plant artificial chromosome technology and its potential application in genetic engineering. AB - Genetic engineering with just a few genes has changed agriculture in the last 20 years. The most frequently used transgenes are the herbicide resistance genes for efficient weed control and the Bt toxin genes for insect resistance. The adoption of the first-generation genetically engineered crops has been very successful in improving farming practices, reducing the application of pesticides that are harmful to both human health and the environment, and producing more profit for farmers. However, there is more potential for genetic engineering to be realized by technical advances. The recent development of plant artificial chromosome technology provides a super vector platform, which allows the management of a large number of genes for the next generation of genetic engineering. With the development of other tools such as gene assembly, genome editing, gene targeting and chromosome delivery systems, it should become possible to engineer crops with multiple genes to produce more agricultural products with less input of natural resources to meet future demands. PMID- 26369911 TI - Use of Polyclonal Intravenous Immunoglobulin at a Paediatric Referral Hospital in South Africa Between 2009 and 2012. AB - BACKGROUND: Polyvalent intravenous immunoglobulin (IVIG) is registered for a limited number of specific indications in South Africa but is increasingly being used for unregistered uses. No guideline exists nationally to monitor and control IVIG prescription, which results in its use in many clinical situations with varying levels of evidence. PURPOSE: This study describes the registered and unregistered use, and cost of IVIG at a tertiary paediatric hospital in South Africa. METHODS: A cross sectional descriptive study design was employed. Data on all patients (0 to 18 years) who attended the hospital during a 39 month period from 2009 to 2012 as out- or inpatients and were dispensed IVIG, was obtained from the pharmacy dispensing and National Health Laboratory Service electronic databases, and supplemented by a patient record review. RESULTS: During the study period, 185 patients received at least one dose of IVIG and a total 916 issues (3641.5 g) were dispensed. In 70 (41 %) of the 171 patients (involving 398 IVIG issues, 46 %), the South African Medicines Control Council registered indications for its use were followed. IVIG accounted for between 1.6, 1.7 and 4.6 % of the annual pharmacy expenditure during this 3-year study period. CONCLUSIONS: More than half of all IVIG dispensed at this paediatric hospital was used for unregistered indications. Considering the pressures on supply and the pharmaceutical costs, a more standardized, protocol-driven approach to the prescription of IVIG is called for. PMID- 26369912 TI - Rescue from Sexually Dimorphic Neuronal Cell Death by Estradiol and PI3 Kinase Activity. AB - Responses of primary hippocampal and cortical neurons derived from male and female rats to cellular stressors were studied. It is demonstrated that 17beta estradiol (E2), a potent neuroprotectant, protected the female neurons but had no effects on the male neurons from CoCl2- and glutamate-induced toxicity. Agonists of the estrogen receptor (ER) subtypes ERalpha and ERbeta, DPN and PPT, respectively, had similar effects to E2. By contrast, effects of E2 were abolished by the ER antagonist ICI-182780, further corroborating the neuroprotective role of ERs. In male neurons, CoCl2 predominately activated the apoptosis-inducing factor (AIF)-dependent pathway and AIF translocation from the cytosol to the nucleus. In comparison, CoCl2 activated the caspase pathway and cytochrome c release in female neurons. The inhibitors of these pathways, namely DiQ for AIF and zVAD for caspase, specifically rescued CoCl2-induced cell death in male and female neurons, respectively. When zVAD and ICI-182780, and E2 were applied in combination, it was demonstrated E2 acted on the caspase pathway leading to female-specific neuroprotection. Furthermore, the PI3 kinase (PI3K) inhibitor blocked the rescue effects of DiQ and zVAD on the male and female neurons, respectively, suggesting that PI3K is a common upstream regulator for both pathways. The present study suggested that both sex-specific and nonspecific mechanisms played a role in neuronal responses to stressors and protective reagents. PMID- 26369913 TI - Prediction of Leymus arenarius (L.) antimicrobial peptides based on de novo transcriptome assembly. AB - Leymus arenarius is a unique wild growing Poaceae plant exhibiting extreme tolerance to environmental conditions. In this study we for the first time performed whole-transcriptome sequencing of lymegrass seedlings using Illumina platform followed by de novo transcriptome assembly and functional annotation. Our goal was to identify transcripts encoding antimicrobial peptides (AMPs), one of the key components of plant innate immunity. Using the custom software developed for this study that predicted AMPs and classified them into families, we revealed more than 160 putative AMPs in lymegrass seedlings. We classified them into 7 families based on their cysteine motifs and sequence similarity. The families included defensins, thionins, hevein-like peptides, snakins, cyclotide, alfa-hairpinins and LTPs. This is the first communication about the presence of almost all known AMP families in trascriptomic data of a single plant species. Additionally, cysteine-rich peptides that potentially represent novel families of AMPs were revealed. We have confirmed by RT-PCR validation the presence of 30 transcripts encoding selected AMPs in lymegrass seedlings. In summary, the presented method of pAMP prediction developed by us can be applied for relatively fast and simple screening of novel components of plant immunity system and is well suited for whole-transcriptome or genome analysis of uncharacterized plants. PMID- 26369914 TI - Novel X-ray image noise reduction technology reduces patient radiation dose while maintaining image quality in coronary angiography. AB - AIMS: The consequences of high radiation dose for patient and staff demand constant improvements in X-ray dose reduction technology. This study assessed non inferiority of image quality and quantified patient dose reduction in interventional cardiology for an anatomy-specific optimised cine acquisition chain combined with advanced real-time image noise reduction algorithms referred to as 'study cine', compared with conventional angiography. METHODS: Fifty patients underwent two coronary angiographic acquisitions: one with advanced image processing and optimised exposure system settings to enable dose reduction (study cine) and one with standard image processing and exposure settings (reference cine). The image sets of 39 patients (18 females, 21 males) were rated by six experienced independent reviewers, blinded to the patient and image characteristics. The image pairs were randomly presented. Overall 85 % of the study cine images were rated as better or equal quality compared with the reference cine (95 % CI 0.81-0.90). The median dose area product per frame decreased from 55 to 26 mGy.cm(2)/frame (53 % reduction, p < 0.001). CONCLUSION: This study demonstrates that the novel X-ray imaging technology provides non inferior image quality compared with conventional angiographic systems for interventional cardiology with a 53 % patient dose reduction. PMID- 26369915 TI - Protein modeling and molecular dynamics simulation of SlWRKY4 protein cloned from drought tolerant tomato (Solanum habrochaites) line EC520061. AB - WRKY genes are members of one of the largest families of plant transcription factors and play an important role in response to biotic and abiotic stresses, and overall growth and development. Understanding the interaction of WRKY proteins with other proteins/ligands in plant cells is of utmost importance to develop plants having tolerance to biotic and abiotic stresses. The SlWRKY4 gene was cloned from a drought tolerant wild species of tomato (Solanum habrochaites) and the secondary structure and 3D modeling of this protein were predicted using Schrodinger Suite-Prime. Predicted structures were also subjected to plot against Ramachandran's conformation, and the modeled structure was minimized using Macromodel. Finally, the minimized structure was simulated in the water environment to check the protein stability. The behavior of the modeled structure was well-simulated and analyzed through RMSD and RMSF of the protein. The present work provides the modeled 3D structure of SlWRKY4 that will help in understanding the mechanism of gene regulation by further in silico interaction studies. PMID- 26369916 TI - Geometric description and electronic properties of the principal photosynthetic pigments of higher plants: a DFT study. AB - The geometric parameters, local and global chemical reactivity parameters (such as the ionization potential, electron affinity, electronegativity, hardness, softness, chemical potential, and electrophilicity index), as well as the energy levels (HOMO/LUMO) and HOMO-LUMO energy gaps have been determined for the principal carotenoids in higher plants. DFT calculations performed using the B3LYP functional in combination with the 6-31G(d,p) (for geometric parameters) and 6-31 + G(d,p) (for energy parameters) basis sets were carried out to study these structures. The HOMO-LUMO energy gaps obtained with the TPSSh functional were compared with the corresponding energy gaps obtained with B3LYP (when both functionals were used with the 6-31 + G(d,p) basis set). Upon analyzing all of the calculated parameters of the studied molecules, both carotenes were found to be the most reactive, followed by beta-cryptoxanthin, zeaxanthin, lutein, violaxanthin, and finally neoxanthin, the least reactive molecule. The results reveal that all of the carotenoids show very high coplanarity in the photochemically active region, resulting in small HOMO-LUMO energy gaps. The calculated local and global chemical reactivity parameters indicate that all of the studied molecules may be classified as soft, as they are good electron donors/acceptors, making these molecules good candidates for use in artificial photosynthetic systems. PMID- 26369917 TI - Synergistic and diminutive effects between halogen bond and lithium bond in complexes involving aromatic compounds. AB - Quantum chemical calculations have been performed to study the interplay between halogen bond and lithium bond in the ternary systems FX-C6H5CN-LiF, FLi-C6H5CN XF, and FLi-C6H5X-NH3 (X = Cl, Br, and I) involving aromatic compounds. This effect was studied in terms of interaction energy, electron density, charge transfer, and orbital interaction. The results showed that both FX-C6H5CN-LiF and FLi-C6H5CN-XF exhibit diminutive effects with the weakening of halogen bond and lithium bond, while FLi-C6H5X-NH3 displays synergistic effects with the strengthening of halogen bond and lithium bond. The nature of halogen bond and lithium bond in the corresponding binary complexes has been unveiled by the quantum theory of atoms in molecules methodology and energy decomposition analysis. PMID- 26369918 TI - Charge transfer and first hyperpolarizability: cage-like radicals C59X and lithium encapsulated Li@C59X (X=B, N). AB - Very recently, two new cage-like radicals (C59B and C59N) formed by a boron or nitrogen atom substituting one carbon atom of C60 were synthesized and characterized. In order to explore the structure-property relationships of combination the cage-like radical and alkali metal, the endohedral Li@C59B and Li@C59N are designed by lithium (Li) atom encapsulated into the cage-like radicals C59B and C59N. Further, the structures, natural bond orbital (NBO) charges, and nonlinear optical (NLO) responses of C59B, C59N, Li@C59B, and Li@C59N were investigated by quantum chemical method. Three density functional methods (BHandHLYP, CAM-B3LYP, and M05-2X) were employed to estimate their first hyperpolarizabilities (beta tot) and obtained the same trend in the beta tot value. The beta tot values by BHandHLYP functional of the pure cage-like radicals C59B (1.30 * 10(3) au) and C59N (1.70 * 10(3) au) are close to each other. Interestingly, when one Li atom encapsulated into the electron-rich radical C59N, the beta tot value of the Li@C59N increases to 2.46 * 10(3) au. However, when one Li atom encapsulated into the electron-deficient radical C59B, the beta tot value of the Li@C59B sharply decreases to 1.54 * 10(2) au. The natural bond orbital analysis indicates that the encapsulated Li atom leads to an obvious charge transfer and valence electrons distribution plays a significant role in the beta tot value. Further, frontier molecular orbital explains that the interesting charge transfer between the encapsulated Li atom and cage-like radicals (C59B and C59N) leads to differences in the beta tot value. It is our expectation that this work will provide useful information for the design of high-performance NLO materials. PMID- 26369919 TI - Modified-Release Formulations of Second-Generation Antiepileptic Drugs: Pharmacokinetic and Clinical Aspects. AB - Modified-release or extended-release (XR) formulations are used to decrease the frequency of dosing for drugs with rapid elimination, to improve convenience and adherence. Use of a modified-release formulation can decrease the peak to trough fluctuations in serum concentrations and theoretically improve the therapeutic benefit of the drug, by decreasing adverse events associated with the higher peak concentrations. Once-daily formulations of lamotrigine (Lamictal XR((r))), levetiracetam (Keppra XR((r))), oxcarbazepine (Oxtellar XR((r)), Apydan((r)) extent) and topiramate (Qudexy XRTM, Trokendi XRTM) are approved for the treatment of focal and/or generalized onset seizures. Other seizure medications have been approved for non-epileptic symptoms. Gabapentin XR (Gralise((r))) is approved for the treatment of post-herpetic neuralgias. Gabapentin enacarbil XR (Horizant((r))) is a prodrug of gabapentin and is indicated for treatment of post herpetic neuralgia and restless leg syndrome, a novel indication. For all but Qudexy XRTM, the tablets/capsules must be swallowed whole, without cutting, crushing or chewing, in order to maintain the XR properties of the formulation. Qudexy XRTM can be swallowed intact or the capsules can be opened and sprinkled onto soft food for those with swallowing difficulties, for example, children and the elderly. The bioavailability of Gralise((r)) and Horizant((r)) is significantly affected by food, specifically fat content, and should be taken with a meal to maximize absorption. Overall, the primary advantage of the newly released XR formulations is the once-daily dosing to improve convenience and adherence, with very limited data suggesting improved tolerability. PMID- 26369920 TI - Maternal Anti-Fetal Brain IgG Autoantibodies and Autism Spectrum Disorder: Current Knowledge and its Implications for Potential Therapeutics. AB - Several studies have found a correlation between the presence of circulating maternal autoantibodies and neuronal dysfunction in the neonate. Specifically, maternal anti-brain autoantibodies, which may access the fetal compartment during gestation, have been identified as one risk factor for developing autism spectrum disorder (ASD). Studies by our laboratory elucidated seven neurodevelopmental proteins recognized by maternal autoantibodies whose presence is associated with a diagnosis of maternal autoantibody-related (MAR) autism in the child. While the specific process of anti-brain autoantibody generation is unclear and the detailed pathogenic mechanisms are currently unknown, identification of the maternal autoantibody targets increases the therapeutic possibilities. The potential therapies discussed in this review provide a framework for possible future medical interventions. PMID- 26369921 TI - Diagnosis, Epidemiology and Management of Mixed States in Bipolar Disorder. AB - Approximately 40% of patients with bipolar disorder experience mixed episodes, defined as a manic state with depressive features, or manic symptoms in a patient with bipolar depression. Compared with bipolar patients without mixed features, patients with bipolar mixed states generally have more severe symptomatology, more lifetime episodes of illness, worse clinical outcomes and higher rates of comorbidities, and thus present a significant clinical challenge. Most clinical trials have investigated second-generation neuroleptic monotherapy, monotherapy with anticonvulsants or lithium, combination therapy, and electroconvulsive therapy (ECT). Neuroleptic drugs are often used alone or in combination with anticonvulsants or lithium for preventive treatment, and ECT is an effective treatment for mixed manic episodes in situations where medication fails or cannot be used. Common antidepressants have been shown to worsen mania symptoms during mixed episodes without necessarily improving depressive symptoms; thus, they are not recommended during mixed episodes. A greater understanding of pathophysiological processes in bipolar disorder is now required to provide a more accurate diagnosis and new personalised treatment approaches. Targeted, specific treatments developed through a greater understanding of bipolar disorder pathophysiology, capable of affecting the underlying disease processes, could well prove to be more effective, faster acting, and better tolerated than existing therapies, therefore providing better outcomes for individuals affected by bipolar disorder. Until such time as targeted agents are available, second generation neuroleptics are emerging as the treatment of choice in the management of mixed states in bipolar disorder. PMID- 26369922 TI - Pretreatment for substance-abusing people with intellectual disabilities: intervening on autonomous motivation for treatment entry. AB - BACKGROUND: Despite a lack of consensus regarding prevalence rates of substance abuse, people with intellectual disabilities (ID) on average use substances slightly less often than their non-disabled peers. However, their use of substances is more often problematic. Avoidance of treatment is a crucial problem among substance-abusing people with ID. This study tested a motivational intervention to facilitate autonomous motivation (i.e. wanting to change substance abuse because of a sense of free choice and volition) for engaging with a subsequent addiction treatment. METHOD: A multiple-case experimental design (N = 6) was conducted to measure day-to-day motivation to change substance abuse among individuals with mild ID (N = 3) and borderline level of intellectual functioning (N = 3) in the Netherlands. The participants (five men, one woman) lived in the community (except one, he lived in a residential facility) and abused cannabis, alcohol or hashish. During the intervention phase, the 10 session treatment programme 'Beat the kick' was delivered by an experienced psychologist, based on motivational interviewing techniques adapted for people with mild to borderline ID. Participants completed an adaptive self-reported inventory based on self-determination theory (SDT) two to three times a week during baseline, intervention and 1-month follow-up. RESULTS: The results of five of the six participants (one dropped out) showed that the type of motivation changed from more controlled types of motivation (i.e. external motivation and introjected motivation) at baseline to more autonomous types of motivation after completion of the intervention. In addition, the participants reported a significant increase in overall need satisfaction and autonomy satisfaction and a significant decrease of overall need frustration. CONCLUSIONS: The implementation of SDT and motivational interviewing principles in the treatment programme 'Beat the kick' reliably changed the type of motivation. In addition, the experimental effects provide initial proof of the use and applicability of SDT among people with ID. PMID- 26369923 TI - Dr. William 'Bill' E. Shiels II (April 2, 1954 - May 5, 2015). PMID- 26369924 TI - Inhibiting prepotent responses in the elderly: Distraction and disinhibition. AB - In this study, we aimed to examine whether older adults, relative to younger adults, suffer from generic inhibition, selective inhibition, and/or distraction deficits, as assessed by behavioral and electrophysiological measures in a go/no go task paradigm that included manipulations of no-go stimulus type (irrelevant vs. conflict) and no-go probability. A total of 96 individuals were recruited; each of three experiments included 32 participants (16 adults above and 16 adults below 60 years of age). The older adults performed more poorly than the younger adults in our behavioral test; however, the event-related potential results showed that irrelevant and conflict no-go stimuli incurred different processes that were differentially impacted by aging, as was reflected in the N2 and P3. That is, the older adults' inhibition deficits might be due to different underlying mechanisms: disproportionate processing of irrelevant no-go stimuli, and disproportionate suppression of conflicting information when executing or withholding a response to conflict no-go stimuli. The present results therefore support the theories of age-related selective inhibition and distraction deficits. PMID- 26369926 TI - An ethnobotanical survey of medicinal plants in Trinidad. AB - BACKGROUND: An ethnobotanical survey was conducted on the Caribbean island of Trinidad to identify medicinal plants commonly used in traditional medicine to treat a variety of medical conditions. METHODS: A pilot survey was conducted to identify the top ten most common ailments where medicinal plants were used. The results of the foregoing study guided a wider national survey conducted between October 2007 and July 2008. A total of 450 households from 50 rural communities were interviewed using the TRAMIL (Traditional Medicine in the Islands) questionnaire for data collection. Details of plants, part(s) used, and remedy formulations were elicited from informants and voucher specimens collected for identification at the National Herbarium of Trinidad and Tobago. The TRAMIL methodology set a limit of a plant with 20 % or more citations for any particular ailment as having significant or popular use. RESULTS: At the end of the survey 917 single plant remedies were identified. The majority of species were from the following families; Asteraceae, Lamiaceae, Leguminosae, Verbenaceae and Poaceae. Applying the TRAMIL 20 % citation of a plant for popular use as significant, Leonotis nepetifolia (for cough/common cold), Gomphrena globosa (for "stoppage-of water"), Curcuma longa and Senna occidentalis (for "afterbirth"), Cymbopogon citratus and Neurolaena lobata (for fever), and Citrus limon (for kidney stones) qualified in our study. Those not reaching the TRAMIL 20 % significant (popular) use were Stachytarpheta jamaicensis (L.) Vahl, Senna alata (L.) Roxb.and Momordica charantia L. which were widely used as "'cooling/cleanser'" in our survey. CONCLUSIONS: Our survey showed significant retention of traditional knowledge of medicinal plants in rural Trinidad. More interestingly, a large remnant of medico-cultural concepts such as "cooling/cleanser", "afterbirth", "stoppage-of-water" and "womb infection" persist in the rural population. Although the scientific literature show that some of the cited plants possessed antimicrobial, anti-inflammatory and related pharmacological activities in laboratory studies, these results must be taken with caution until clinical trials are conducted to establish safety and efficacy. PMID- 26369925 TI - Growth hormone therapy in children with CKD after more than two decades of practice. AB - This review focuses on the evidence for the efficacy and safety of recombinant human growth hormone (rhGH) therapy in children with all stages of chronic kidney disease (CKD) and at all ages. It describes the improving height prognosis for our patients both with and without rhGH; explains the underlying hormonal abnormalities that provide the rationale for rhGH use in CKD and the endocrine changes that accompany treatment; and views on who warrants treatment, with what dose, and how long for. PMID- 26369927 TI - De novo assembly of the mitochondrial genome of Ulva fasciata Delile (Ulvophyceae, Chlorophyta), a distromatic blade-forming green macroalga. AB - We present the 61 614 bp circular-mapping mitochondrial genome of Ulva fasciata. Fifty-eight genes were identified including 29 protein-coding genes, 27 transfer RNA (tRNA) genes, and two ribosomal RNA (rRNA) genes. Four ORFs from the Ulva sp. UNA00071828 mitogenome were conserved compared to the mitogenome of Ulva fasciata. The ~10 000 bp size difference was mostly due to fewer introns found in U. fasciata mtDNA (4) as compared with the Ulva sp. UNA00071828 mtDNA (10). Introns were annotated in cox1 (3) and nad3 (1). The AT content was similar to Ulva sp. UNA00071828 mtDNA at 67.5%. A phylogenomic anaylsis of 28 chlorophytes and 17 protein-coding genes (14 115 bp alignment) showed that U. fasciata clusters closely with other members of the Ulvophyceae (Ulva sp. UNA00071828, Pseudendoclonium akinetum, and Oltmannsiellopsis viridis). This analysis did not recover a monophyletic Ulvophyceae, however, the Trebouxiophyceae and Chlorophyceae were supported as monophyletic groups. PMID- 26369928 TI - Eating locally: Australasian gannets increase their foraging effort in a restricted range. AB - During the breeding season, seabirds adopt a central place foraging strategy and are restricted in their foraging range by the fasting ability of their partner/chick and the cost of commuting between the prey resources and the nest. Because of the spatial and temporal variability of marine ecosystems, individuals must adapt their behaviour to increase foraging success within these constraints. The at-sea movements, foraging behaviour and effort of the Australasian gannet (Morus serrator) was determined over three sequential breeding seasons of apparent differing prey abundance to investigate how the species adapts to inter annual fluctuations in food availability. GPS and tri-axial accelerometer data loggers were used to compare the degree of annual variation within two stages of breeding (incubation and chick rearing) at a small gannet colony situated between two larger, nearby colonies. Interestingly, neither males nor females increased the total distance travelled or duration of foraging trip in any breeding stage (P>0.05 in all cases) despite apparent low prey availability. However, consistently within each breeding stage, mean vectorial dynamic body acceleration (an index of energy expenditure) was greater in years of poorer breeding success (increased by a factor of three to eight), suggesting birds were working harder within their range. Additionally, both males and females increased the proportion of a foraging trip spent foraging in a poorer year across both breeding stages. Individuals from this colony may be limited in their ability to extend their range in years of low prey availability due to competition from conspecifics in nearby colonies and, consequently, increase foraging effort within this restricted foraging area. PMID- 26369929 TI - Vimentin is involved in regulation of mitochondrial motility and membrane potential by Rac1. AB - In this study we show that binding of mitochondria to vimentin intermediate filaments (VIF) is regulated by GTPase Rac1. The activation of Rac1 leads to a redoubling of mitochondrial motility in murine fibroblasts. Using double-mutants Rac1(G12V, F37L) and Rac1(G12V, Y40H) that are capable to activate different effectors of Rac1, we show that mitochondrial movements are regulated through PAK1 kinase. The involvement of PAK1 kinase is also confirmed by the fact that expression of its auto inhibitory domain (PID) blocks the effect of activated Rac1 on mitochondrial motility. The observed effect of Rac1 and PAK1 kinase on mitochondria depends on phosphorylation of the Ser-55 of vimentin. Besides the effect on motility Rac1 activation also decreases the mitochondrial membrane potential (MMP) which is detected by ~20% drop of the fluorescence intensity of mitochondria stained with the potential sensitive dye TMRM. One of important consequences of the discovered regulation of MMP by Rac1 and PAK1 is a spatial differentiation of mitochondria in polarized fibroblasts: at the front of the cell they are less energized (by ~25%) than at the rear part. PMID- 26369930 TI - Modeling dioxygenase enzyme kinetics in familial paraganglioma. AB - Hypoxia inducible factors (HIFs) play vital roles in cellular maintenance of oxygen homeostasis. These transcription factors are responsible for the expression of genes involved in angiogenesis, metabolism, and cell proliferation. Here, we generate a detailed mathematical model for the enzyme kinetics of alpha ketoglutarate-dependent HIF prolyl 4-hydroxylase domain (PHD) dioxygenases to simulate our in vitro data showing synergistic PHD inhibition by succinate and hypoxia in experimental models of succinate dehydrogenase loss, which phenocopy familial paraganglioma. Our mathematical model confirms the inhibitory synergy of succinate and hypoxia under physiologically-relevant conditions. In agreement with our experimental data, the model predicts that HIF1alpha is not stabilized under atmospheric oxygen concentrations, as observed. Further, the model confirms that addition of alpha-ketoglutarate can reverse PHD inhibition by succinate and hypoxia in SDH-deficient cells. PMID- 26369931 TI - A zebrafish model of inflammatory lymphangiogenesis. AB - Inflammatory bowel disease (IBD) is a disabling chronic inflammatory disease of the gastrointestinal tract. IBD patients have increased intestinal lymphatic vessel density and recent studies have shown that this may contribute to the resolution of IBD. However, the molecular mechanisms involved in IBD-associated lymphangiogenesis are still unclear. In this study, we established a novel inflammatory lymphangiogenesis model in zebrafish larvae involving colitogenic challenge stimulated by exposure to 2,4,6-trinitrobenzenesulfonic acid (TNBS) or dextran sodium sulphate (DSS). Treatment with either TNBS or DSS resulted in vascular endothelial growth factor receptor (Vegfr)-dependent lymphangiogenesis in the zebrafish intestine. Reduction of intestinal inflammation by the administration of the IBD therapeutic, 5-aminosalicylic acid, reduced intestinal lymphatic expansion. Zebrafish macrophages express vascular growth factors vegfaa, vegfc and vegfd and chemical ablation of these cells inhibits intestinal lymphatic expansion, suggesting that the recruitment of macrophages to the intestine upon colitogenic challenge is required for intestinal inflammatory lymphangiogenesis. Importantly, this study highlights the potential of zebrafish as an inflammatory lymphangiogenesis model that can be used to investigate the role and mechanism of lymphangiogenesis in inflammatory diseases such as IBD. PMID- 26369932 TI - Endothelial cell division in angiogenic sprouts of differing cellular architecture. AB - The vasculature of the zebrafish trunk is composed of tubes with different cellular architectures. Unicellular tubes form their lumen through membrane invagination and transcellular cell hollowing, whereas multicellular vessels become lumenized through a chord hollowing process. Endothelial cell proliferation is essential for the subsequent growth and maturation of the blood vessels. However, how cell division, lumen formation and cell rearrangement are coordinated during angiogenic sprouting has so far not been investigated at detailed cellular level. Reasoning that different tubular architectures may impose discrete mechanistic constraints on endothelial cell division, we analyzed and compared the sequential steps of cell division, namely mitotic rounding, cytokinesis, actin re-distribution and adherence junction formation, in different blood vessels. In particular, we characterized the interplay between cell rearrangement, mitosis and lumen dynamics within unicellular and multicellular tubes. The lumen of unicellular tubes becomes constricted and is ultimately displaced from the plane of cell division, where a de novo junction forms through the recruitment of junctional proteins at the site of abscission. By contrast, the new junctions separating the daughter cells within multicellular tubes form through the alteration of pre-existing junctions, and the lumen is retained throughout mitosis. We also describe variations in the progression of cytokinesis: while membrane furrowing between daughter cells is symmetric in unicellular tubes, we found that it is asymmetric in those multicellular tubes that contained a taut intercellular junction close to the plane of division. Our findings illustrate that during the course of normal development, the cell division machinery can accommodate multiple tube architectures, thereby avoiding disruptions to the vascular network. PMID- 26369933 TI - Association Between Nighttime Discharge from the Intensive Care Unit and Hospital Mortality: A Multi-Center Retrospective Cohort Study. AB - BACKGROUND: We aimed to determine the impact of nighttime discharge from the intensive care unit (ICU) to the ward on hospital mortality and readmission rates in consecutive critically ill patients admitted to five Canadian ICUs. We hypothesized that hospital mortality and readmission rates would be higher for patients discharged after hours compared with discharge during the day. METHODS: A multi-center retrospective cohort study was carried out at five hospitals in Edmonton, Canada, between July 2002 and December 2009. Nighttime discharge was defined as discharge from the ICU occurring between 07:00 pm and 07:59 am. Logistic regression analysis was used to explore the associations between nighttime discharge and outcomes. RESULTS: Of 19,622 patients discharged alive from the ICU, 3,505 (17.9%) discharges occurred during nighttime. Nighttime discharge occurred more commonly among medical than surgical patients (19.9% vs. 13.8%, P < 0.001) and among those with more comorbid conditions, compared with daytime discharged patients. Crude hospital mortality (11.8% versus 8.8%, P < 0.001) was greater for nighttime discharged as compared to daytime discharged patients. In a multivariable analysis, after adjustment for comorbidities, diagnosis and source of admission, nighttime discharge remains associated with higher mortality (odds ratio [OR] 1.29; 95% CI, 1.14 to 1.46, P < 0.001). This finding was robust in two sensitivity analyses examining discharges occurring between 00:00 am and 04:59 am (OR 1.28; 1.12-1.47; P < 0.001) and for those who died within 48 h of ICU discharge without readmission (OR 1.24; 1.07-1.42, P = 0.002). There was no difference in ICU readmission for nighttime compared with daytime discharges (7.4% vs. 6.9 %, p = 0.26). However, rates were higher for nighttime discharges in community compared with tertiary hospitals (7.7% vs. 5.7%, P = 0.023). CONCLUSIONS: In a large integrated health region, 1 in 5 ICU patients are discharged at nighttime, a factor with increasing occurrence during our study and shown to be independently associated with higher hospital mortality. PMID- 26369934 TI - Simultaneous decontamination and drying of rough rice using combined pulsed light and holding treatment. AB - BACKGROUND: Pulsed light (PL) technology has been proven effective in food disinfection. However, increasing the light intensity or treatment time could swiftly increase the temperature of the food product. Using the thermal effect in an appropriate way may achieve a simultaneous disinfection and drying effect. The objective of this study was to investigate the feasibility of simultaneous disinfection and drying of rough rice using PL and holding treatment. RESULTS: Freshly harvested rice samples were inoculated by Aspergillus flavus (A. flavus) and treated using PL under different intensities and durations followed by holding treatment. The PL treatment under intensity of 1.08 W cm(-2) for 21 s led to a reduction of 0.29 log cfu g(-1) on the population size of A. flavus spores. After holding treatment, a 5.2 log cfu g(-1) reduction was achieved. The corresponding total moisture removal reached 3.3% points. No adverse effect on milling quality was detected after the treatment. CONCLUSION: The obtained results revealed that the combined PL and holding treatment had good potential for successful application in the rice industry to simultaneously achieve disinfection and drying. (c) 2015 Society of Chemical Industry. PMID- 26369935 TI - Shortening a loop can increase protein native state entropy. AB - Protein loops are essential structural elements that influence not only function but also protein stability and folding rates. It was recently reported that shortening a loop in the AcP protein may increase its native state conformational entropy. This effect on the entropy of the folded state can be much larger than the lower entropic penalty of ordering a shorter loop upon folding, and can therefore result in a more pronounced stabilization than predicted by polymer model for loop closure entropy. In this study, which aims at generalizing the effect of loop length shortening on native state dynamics, we use all-atom molecular dynamics simulations to study how gradual shortening a very long or solvent-exposed loop region in four different proteins can affect their stability. For two proteins, AcP and Ubc7, we show an increase in native state entropy in addition to the known effect of the loop length on the unfolded state entropy. However, for two permutants of SH3 domain, shortening a loop results only with the expected change in the entropy of the unfolded state, which nicely reproduces the observed experimental stabilization. Here, we show that an increase in the native state entropy following loop shortening is not unique to the AcP protein, yet nor is it a general rule that applies to all proteins following the truncation of any loop. This modification of the loop length on the folded state and on the unfolded state may result with a greater effect on protein stability. PMID- 26369936 TI - CD8(+)NKT-like cells regulate the immune response by killing antigen-bearing DCs. AB - CD1d-dependent NKT cells have been extensively studied; however, the function of CD8(+)NKT-like cells, which are CD1d-independent T cells with NK markers, remains unknown. Here, we report that CD1d-independent CD8(+)NKT-like cells, which express both T cell markers (TCRbeta and CD3) and NK cell receptors (NK1.1, CD49b and NKG2D), are activated and significantly expanded in mice immunized with GFP expressing dendritic cells. Distinct from CD1d-dependent NKT cells, CD8(+)NKT like cells possess a diverse repertoire of TCRs and secrete high levels of IFN gamma but not IL-4. CD8(+)NKT-like cell development is normal in CD1d(-/-) mice, which suggests that CD8(+)NKT-like cells undergo a unique development pathway that differs from iNKT cells. Further functional analyses show that CD8(+)NKT like cells suppress T-cell responses through elimination of dendritic cells in an antigen-specific manner. Adoptive transfer of antigen-specific CD8(+)NKT-like cells into RIP-OVA mice prevented subsequent development of diabetes in the animals induced by activated OT-I CD8 T cells. Our study suggests that CD8(+)NKT like cells can function as antigen-specific suppressive cells to regulate the immune response through killing antigen-bearing DCs. Antigen-specific down regulation may provide an active and precise method for constraining an excessive immune response and avoiding bypass suppression of necessary immune responses to other antigens. PMID- 26369937 TI - Identification and expression profiles of sRNAs and their biogenesis and action related genes in male and female cones of Pinus tabuliformis. AB - BACKGROUND: Small RNA (sRNA) play pivotal roles in reproductive development, and their biogenesis and action mechanisms are well characterised in angiosperm plants; however, corresponding studies in conifers are very limited. To improve our understanding of the roles of sRNA pathways in the reproductive development of conifers, the genes associated with sRNA biogenesis and action pathways were identified and analysed, and sRNA sequencing and parallel analysis of RNA ends (PARE) were performed in male and female cones of the Chinese pine (Pinus tabuliformis). RESULTS: Based on high-quality reference transcriptomic sequences, 21 high-confidence homologues involved in sRNA biogenesis and action in P. tabuliformis were identified, including two different DCL3 genes and one AGO4 gene. More than 75 % of genes involved in sRNA biogenesis and action have higher expression levels in female than in male cones. Twenty-six microRNA (miRNA) families and 74 targets, including 46 24-nt sRNAs with a 5' A, which are specifically expressed in male cones or female cones and probably bind to AGO4, were identified. CONCLUSIONS: The sRNA pathways have higher activity in female than in male cones, and the miRNA pathways are the main sRNA pathways in P. tabuliformis. The low level of 24-nt short-interfering RNAs in conifers is not caused by the absence of biogenesis-related genes or AGO-binding proteins, but most likely caused by the low accumulation of these key components. The identification of sRNAs and their targets, as well as genes associated with sRNA biogenesis and action, will provide a good starting point for investigations into the roles of sRNA pathways in cone development in conifers. PMID- 26369939 TI - High-level expression of a recombinant active microbial transglutaminase in Escherichia coli. AB - BACKGROUND: Bacterial transglutaminases are increasingly required as industrial reagents for in vitro modification of proteins in different fields such as in food processing as well as for enzymatic site-specific covalent conjugation of therapeutic proteins to polyethylene glycol to get derivatives with improved clinical performances. In this work we studied the production in Escherichia coli of a recombinant transglutaminase from Streptomyces mobaraensis (microbial transglutaminase or MTGase) as enzymatically active chimeric forms using different expression systems under the control of both lac promoter or thermoinducible phage lambda promoter. RESULTS: Thermoinducible and constitutive expression vectors were constructed expressing Met-MTGase with chimeric LacZ1 8PNP1-20 or LacZ1-8 fusion protein under different promoters. After transformed in competent Escherichia coli K12 strains were fermented in batch and fed-bach mode in different mediums in order to select the best conditions of expression. The two most performing fusion protein systems namely short thermoinducible LacZ1 8Met-MTGase from NP668/1 and long constitutive LacZ1-8PNP1-20Met-MTGase from NP650/1 has been chosen to compare both efficiency of expression and biochemical qualities of the product. Proteins were extracted, purified to homogeneity and verified as a single peak obtained in RP-HPLC. The LacZ1-8PNP1-20Met-MTGase fusion protein purified from NP650/1 exhibited an activity of 15 U/mg compared to 24 U/mg for the shorter fusion protein purified from NP668/1 cell strain. CONCLUSIONS: Combining the experimental data on expression levels and specific activities of purified MTGase fusion proteins, the chimeric LacZ1-8Met-MTGase, which displays an enzymatic activity comparable to the wild-type enzyme, was selected as a candidate for producing microbial transglutaminase for industrial applications. PMID- 26369940 TI - Global Analysis of Protein Lysine Succinylation Profiles and Their Overlap with Lysine Acetylation in the Marine Bacterium Vibrio parahemolyticus. AB - Protein lysine acylation, including acetylation and succinylation, has been found to be a major post-translational modification (PTM) and is associated with the regulation of cellular processes that are widespread in bacteria. Vibrio parahemolyticus is a model marine bacterium that causes seafood-borne illness in humans worldwide. The lysine acetylation of V. parahemolyticus has been extensively characterized in our previous work, and here, we report the first global analysis of lysine succinylation and the overlap between the two types of acylation in this bacterium. Using high-accuracy nano liquid chromatography tandem mass spectrometry combined with affinity purification, we identified 1931 lysine succinylated peptides matched on 642 proteins, with the quantity of the succinyl-proteins accounting for 13.3% of the total proteins in cells. Bioinformatics analysis results showed that these succinylated proteins are involved in almost every cellular process, particularly in protein biosynthesis and metabolism, and are distributed in diverse subcellular compartments. Moreover, several sequence motifs were identified, including succinyl-lysine flanked by a lysine or arginine residue at the -8, -7, or +7 position and without these residues at the -1 or +2 position, and these motifs differ from those found in other bacteria and eukaryotic cells. Furthermore, a total of 517 succinyl lysine sites (26.7%) on 288 proteins (44.9%) were also found to be acetylated, suggesting extensive overlap between succinylation and acetylation in this bacterium. This systematic analysis provides a promising starting point for further investigations of the physiologic and pathogenic roles of lysine succinylation and acetylation in V. parahemolyticus. PMID- 26369938 TI - Hydrogen peroxide - production, fate and role in redox signaling of tumor cells. AB - Hydrogen peroxide (H2O2) is involved in various signal transduction pathways and cell fate decisions. The mechanism of the so called "redox signaling" includes the H2O2-mediated reversible oxidation of redox sensitive cysteine residues in enzymes and transcription factors thereby altering their activities. Depending on its intracellular concentration and localization, H2O2 exhibits either pro- or anti-apoptotic activities. In comparison to normal cells, cancer cells are characterized by an increased H2O2 production rate and an impaired redox balance thereby affecting the microenvironment as well as the anti-tumoral immune response. This article reviews the current knowledge about the intracellular production of H2O2 along with redox signaling pathways mediating either the growth or apoptosis of tumor cells. In addition it will be discussed how the targeting of H2O2-linked sources and/or signaling components involved in tumor progression and survival might lead to novel therapeutic targets. PMID- 26369941 TI - Unintentional Continuation of Medications Intended for Acute Illness After Hospital Discharge: A Population-Based Cohort Study. AB - BACKGROUND: Patients are vulnerable to medication-related errors during transitions in care. Patients discharged from acute care hospitals may be at an elevated risk for the unintentional continuation of medications prescribed to prevent or treat complications that are associated with acute illness but are no longer indicated. We sought to evaluate rates of (primary objective) and risk factors for (secondary objective) potentially unintentional medication continuation following hospitalization. METHODS: A population-based cohort study of more than one million patients 66 years of age or older who were hospitalized in Ontario, Canada, between 2003 and 2011 and followed for 1 year (2004 to 2012). We created distinct cohorts by identifying seniors not previously receiving four classes of medications typically used to treat or prevent complications of acute illness: (1) antipsychotic medications, (2) gastric acid suppressants (histamine 2 blockers and proton pump inhibitors), (3) benzodiazepines, and (4) inhaled bronchodilators and steroids. After excluding documented indications, we followed patients to ascertain whether these medications were continued after hospital discharge, and assessed risk factors for their continuation using generalized estimating equations. The primary outcome was the new dispensation of any of the selected medications within 7 days of hospital discharge. RESULTS: Prescription without documented indication occurred across all medication classes, from 12,209 patients (1.4 %) for antipsychotic medications to 34,140 patients (6.1 %) for gastric acid suppressants. Risk factors for unintentional continuation varied across medication groups, but rates were consistently higher for older patients, those with multiple comorbidities, and emergency hospitalizations. The largest absolute risk factor across all medications was a hospitalization > 7 days [OR 2.03 (95 % CI 1.94-2.11) for respiratory inhalers, 6.35 (95 % CI 5.91-6.82) for antipsychotic medications]. These medications were often continued at 1 year of follow-up, and accounted for a total additional medication cost of over CAD$18 million for the study population. CONCLUSION: Discharged patients are at risk of being prescribed and dispensed medications that are typically intended to prevent or treat complications of acute illness, despite having no documented indication for chronic use. PMID- 26369943 TI - Evaluating clinical competence during nursing education: A comprehensive integrative literature review. AB - This paper explored concepts, definitions and theoretical perspectives evaluating clinical competence during nursing education. The questions were: (i) How is clinical competence evaluated? and (ii) What is evaluated? An integrative review of 19 original research articles from 2009 to 2013 was performed. Results showed that evaluation tools were used in 14, observations in 2 and reflecting writing in 3 studies. The students participated in all but one evaluation alone or together with peers, faculty members or preceptors. Three themes were found: (i) professional practice with a caring perspective; (ii) clinical skills and reflective practice; and (iii) cognitive, affective and psychomotor skills both with a nursing perspective. This review shows an emphasis on structured methods with a risk reducing nursing to tasks and skills why combinations with qualitative evaluations are recommended. A holistic view of competence dominated and in designing evaluations, explicit perspectives and operationalized definitions of clinical competence became evident. PMID- 26369942 TI - beta2-Adrenergic receptor promoter haplotype influences the severity of acute viral respiratory tract infection during infancy: a prospective cohort study. AB - BACKGROUND: Despite the significant interest in beta2-Adrenergic receptor (ADRB2) polymorphisms related to asthma, whether ADRB2 genetic variants are similarly associated with acute respiratory tract infections have not been studied. We hypothesized that genetic variants in ADRB2 associated with a response to asthma therapy during an asthma exacerbation were also associated with severity of acute respiratory tract infections. METHODS: To test this hypothesis, we genotyped 5 common polymorphisms in the promoter region and coding block of the ADRB2 gene (loci -2387, -2274, -1343, +46, and +79) from 374 Caucasian and African American term infants who were enrolled at the time of acute respiratory illness over four respiratory viral seasons. Severity of respiratory tract infections was measured using a bronchiolitis severity score (BSS; range = 0-12, clinically significant difference = 0.5) with a higher score indicating more severe disease. We assigned the promoter, coding and combined promoter and coding haplotypes to the unphased genotype data. The associations between each of these five single-nucleotide polymorphisms (SNPs) as well as the haplotypes and infant BSS were analyzed using nonparametric univariate analysis and multivariable proportional odds model separately in Caucasians and African Americans. RESULTS: There was no significant association between infant BSS and each of the SNPs in both Caucasians and African Americans. However, promoter haplotype CCA was associated with a decreased BSS in African Americans in a dose dependent manner. The median (interquartile range) BSS of infants with no copies of the CCA haplotype, one copy, and two copies of the CCA haplotype were 5.5 (2.0, 8.0), 4.0 (1.0, 7.5), and 3.0 (1.0, 4.0), respectively. This dose dependent relationship persisted after adjusting for infant age, gender, daycare exposure, secondhand smoke exposure, prior history of breastfeeding, siblings at home, and enrollment season (adjusted odds ratio: 0.59, 95% confidence interval: 0.36, 0.98). There was no similar protective relationship of haplotype CCA on severity of respiratory tract infections identified in Caucasians. CONCLUSIONS: ADRB2 genotype may be predictive of severity of acute respiratory tract infections in African Americans, and potentially identify a subset of infants who may respond to beta agonist therapy. PMID- 26369945 TI - Municipal-level differences in depressive symptoms among adolescents in Norway: Results from the cross-national Ungdata study. AB - AIM: This study aimed to investigate municipal-level variations and individual- and municipal-level predictors of high levels of depressive symptoms among Norwegian adolescents. METHODS: We used data from the Norwegian cross-national Ungdata study. We included 77,424 adolescents from 171 municipalities attending junior high school (Grades 8-10; age 13-16 years) from 2011 to 2013. Multilevel (two-level) logistic regression models were applied for the data analyses. RESULTS: The study revealed that 11% of adolescents reported high levels of depressive symptoms. The median odds ratio without adjusting for any individual- or municipal-level predictors was 1.24, indicating a small between-municipalities variability for high levels of depressive symptoms. All individual-level factors, such as gender, school grade, family income, substance use behaviours, bullying and dissatisfaction with different aspects of life, were significantly associated with high levels of depressive symptoms (p < 0.05). As to municipal-level factors, a low annual budgets for municipal health services was the sole significant predictor of high levels of depressive symptoms between municipalities. Municipal-level factors and variables related to survey characteristics explained a moderate proportion of the variation in high levels of depressive symptoms between municipalities. CONCLUSIONS: The cluster heterogeneity in high levels of depressive symptoms was small between municipalities in Norway. Further research should examine the geographic clustering of mental health problems at the school and neighbourhood level. PMID- 26369944 TI - Clinical features and autonomic testing predict survival in multiple system atrophy. AB - Multiple system atrophy is characterized by autonomic failure along with motor symptoms of parkinsonism and/or cerebellar ataxia. There are differing reports on the influence of certain clinical features, including motor subtype (multiple system atrophy-parkinsonism versus multiple system atrophy-cerebellar ataxia), age of onset, gender, and early autonomic symptoms, on the survival in patients with multiple system atrophy. We sought to evaluate overall survival and predictors of survival in a large cohort of patients with multiple system atrophy seen at a single referral centre where objective autonomic testing is routinely performed for this indication. All cases of multiple system atrophy evaluated at Mayo Clinic, Rochester and assessed with an autonomic reflex screen between January 1998 and December 2012 were retrospectively reviewed. A total of 685 patients were identified; 594 met criteria for probable multiple system atrophy, and 91 for possible multiple system atrophy. Multiple system atrophy-parkinsonism was the predominant subtype in 430 patients (63%). Average age of onset was earlier in multiple system atrophy-cerebellar ataxia (58.4 years) compared to multiple system atrophy-parkinsonism (62.3 years; P < 0.001). Median disease duration from symptom onset to death was 7.51 years (95% confidence interval 7.18 7.78) while time from diagnosis to death was 3.33 years (95% confidence interval 2.92-3.59). There was no difference in survival between motor subtypes of multiple system atrophy (P = 0.232). An initial motor symptom was most common (61%) followed by autonomic onset (28%) and combined motor and autonomic symptoms (11%). The initial onset of either motor or autonomic symptoms did not influence length of survival. However, a number of clinical and autonomic laboratory features predicted unfavourable survival in a univariate analysis. A multivariate model retained the following unfavourable predictors of survival: (i) falls within 3 years of onset (hazard ratio 2.31, P < 0.0001); (ii) bladder symptoms (hazard ratio 1.96, P < 0.0001); (iii) urinary catheterization within 3 years of symptom onset (hazard ratio 1.67, P < 0.003); (iv) orthostatic intolerance within 1 year of symptom onset (hazard ratio 1.28, P < 0.014); (v) older age of onset (hazard ratio 1.02, P = 0.001); and (vi) degree of autonomic failure as measured by a validated composite autonomic severity score (hazard ratio 1.07, P < 0.0023). We conclude that carefully selected clinical features can be used to predict survival in patients with multiple system atrophy. Autonomic testing adds an additional, independent predictor of survival, demonstrating its value not only in the diagnosis of multiple system atrophy but also as prognostic marker. PMID- 26369946 TI - Paving the way for universal family planning coverage in Ethiopia: an analysis of wealth related inequality. AB - BACKGROUND: Family planning plays a significant role in reducing maternal and child mortality and ultimately in achieving national and international development goals. It also has an important role in reducing new pediatric HIV infections by preventing unwanted pregnancies among HIV positive women. Investing in family planning is one of the smart investments for development as population dynamics have a fundamental influence on the pillars of sustainable development, including that of a sustainable environment. OBJECTIVE: To identify and quantify wealth related differences in family planning use between poor and rich Ethiopian women based on the Demographic and Health Survey asset based wealth quintiles. METHODS: The proportion of women who used contraceptives during implementation of the 2011 and 2005 Ethiopia Demographic and Health Surveys was calculated across wealth quintiles. Data were stratified for place of residence to analyze and determine inequalities in family planning use separately for rural and urban women. Socioeconomic inequalities according to wealth were measured using the slope index of inequality and the relative index of inequality. RESULT: The absolute difference of contraceptive prevalence between poorest and richest women was over 25.3 percentage points (95% CI = 18.9-31.7) in 2011. Contraceptive use was more than twice (RII: 2.6, 95% CI = 2.0 - 3.3) as prevalent among the richest compared with the poorest. CONCLUSION: Despite efforts to provide contraceptives for free at all public health facilities, wealth based inequalities still prevail in Ethiopia. People at lower socioeconomic strata should be empowered more to avoid the root causes of inequality and to achieve national Health Sector Development Program Goals. PMID- 26369947 TI - Comprehensive Sequence-Flux Mapping of a Levoglucosan Utilization Pathway in E. coli. AB - Synthetic metabolic pathways often suffer from low specific productivity, and new methods that quickly assess pathway functionality for many thousands of variants are urgently needed. Here we present an approach that enables the rapid and parallel determination of sequence effects on flux for complete gene-encoding sequences. We show that this method can be used to determine the effects of over 8000 single point mutants of a pyrolysis oil catabolic pathway implanted in Escherichia coli. Experimental sequence-function data sets predicted whether fitness-enhancing mutations to the enzyme levoglucosan kinase resulted from enhanced catalytic efficiency or enzyme stability. A structure of one design incorporating 38 mutations elucidated the structural basis of high fitness mutations. One design incorporating 15 beneficial mutations supported a 15-fold improvement in growth rate and greater than 24-fold improvement in enzyme activity relative to the starting pathway. This technique can be extended to improve a wide variety of designed pathways. PMID- 26369948 TI - Factors associated with nutritional decline in hospitalised medical and surgical patients admitted for 7 d or more: a prospective cohort study. AB - This prospective cohort study was conducted in eighteen Canadian hospitals with the aim of examining factors associated with nutritional decline in medical and surgical patients. Nutritional decline was defined based on subjective global assessment (SGA) performed at admission and discharge. Data were collected on demographics, medical information, food intake and patients' satisfaction with nutrition care and meals during hospitalisation; 424 long-stay (>=7 d) patients were included; 38% of them had surgery; 51% were malnourished at admission (SGA B or C); 37% had in-hospital changes in SGA; 19.6% deteriorated (14.6% from SGA A to B/C and 5% from SGA B to C); 17.4% improved (10.6% from SGA B to A, 6.8% from SGA C to B/A); and 63.0 % patients were stable (34.4% were SGA A, 21.3% SGA B, 7.3% SGA C). One SGA C patient had weight loss >=5%, likely due to fluid loss and was designated as stable. A subset of 364 patients with admission SGA A and B was included in the multiple logistic regression models to determine factors associated with nutritional decline. After controlling for SGA at admission and the presence of a surgical procedure, lower admission BMI, cancer, two or more diagnostic categories, new in-hospital infection, reduced food intake, dissatisfaction with food quality and illness affecting food intake were factors significantly associated with nutritional decline in medical patients. For surgical patients, only male sex was associated with nutritional decline. Factors associated with nutritional decline are different in medical and surgical patients. Identifying these factors may assist nutritional care. PMID- 26369950 TI - Isolation and Identification of a Red Pigment from the Antarctic Bacterium Shewanella frigidimarina. AB - The present study dealt with the isolation, identification and characterization of pigments from red snow samples of the Quito coastal front glacier (S 62o 27,217', W 059o 45,960') in Greenwich, Archipelago South Shetland, Antarctica, during summer 2013. As a strain of Shewanella was found to be the most common and abundant species with maximum red color production, the pigment -contained in the protein fraction- was isolated and characterized by high performance liquid chromatography (HPLC), two-dimensional fluorescence Difference Gel Electrophoresis (2-D DIGE) and matrix- assisted laser desorption/ionization-time of flight mass spectrometry (MALDI/TOF/TOF). The identified pigment is a cytochrome c3 with apparent molecular weight of 10 kDa and apparent pI around 4.5. The maximum pigment concentration was produced at warm temperatures, 28oC, and with increasing exposure time to UV radiation. Here we demonstrate that the synthesis of cytochrome c3 by the Antarctic bacterium is due to thermal adaptation and/or adaptation to radiation. Further, pigments such as cytochrome c3 enable this bacterial species to use an anaerobic and ferric metabolism. In addition, this study draws attention to the relevance of adaptation investigations; to the study of in vivo monitoring of environmental warming and UV radiation due to global warming; and to the study of the potential habitability of other worlds in the Solar System and beyond. PMID- 26369951 TI - Comparative Two-Dimensional Gel Electrophoresis of Trypanosoma cruzi Mammalian Stage Forms in an Alkaline pH Range. AB - It is estimated that several million people are currently infected worldwide by the protozoan parasite, Trypanosoma cruzi, which causes Chagas disease. After mammalian host infection, a fundamental event is the differentiation from infective trypomastigotes into replicative amastigotes (amastigogenesis) inside host-cells. To unravel the particularities of both forms, it is essential to identify molecules presented in each form. Since T. cruzi gene expression regulation occurs mainly at posttranscriptional level, a proteomic approach is appropriate. Due to intrinsic difficulties with performing 2-DE in the alkaline pH range, there are no reports on 2-DE-based comparative proteome analysis of T. cruzi mammalianstage forms that focus on alkaline polypeptides. Here, we performed a comparative proteome analysis between tissue culture- derived trypomastigotes and extracellular amastigote-like cells using conditions optimized for the 6-11 pH range followed by identification by MALDI-TOF/TOF technology. The alkaline 2-DE maps from both forms show that proteins with a pI above 7.0 were not underrepresented (= 65% of proteins detected). Moreover the differences in protein expression between the Human-hosted T. cruzi forms corroborated previous proteomic studies and corresponded to their biological traits. PMID- 26369952 TI - Identification and Characterization of Two Novel Alpha-D-Galactosidases from Pedobacter heparinus. AB - Two putative alpha-D-galactosidases (alpha-GALs) belonging to glycosyl hydrolase family 27, and originating from the rather unexplored bacterial strain Pedobacter heparinus, were cloned and biochemically characterized. The recombinant enzymes designated as PhAGal729 and PhAGal2920 showed comparable biochemical properties: the optimum pH values were determined to be pH 5.0 and 5.5, and temperature optima lay between 30 degrees C and 37 degrees C, respectively. Both alpha-GALs were not dependent on the presence of divalent metal ions, and the addition of EDTA had no influence on enzymatic activity. The activity of both enzymes substantially increased in the presence of Fe3(+) ions. Both enzymes were inhibited by sodium dodecyl sulfate (SDS) and urea. alpha-GALs from P. heparinus were highly specific in hydrolyzing glycosides with alpha-1,2/3/4 or alpha-1,6 linked galactose to other sugars, whereas other glycosides such as alpha-linked N acetylgalactosamine, N-acetylglucosamine or glucose residues were not released. Nevertheless, neither PhAGal729 nor PhAGal2920 were able to remove alpha-linked galactose epitopes from native human erythrocytes. The facile expression and purification procedures in combination with wide substrate specificities make alpha-GALs from P. heparinus potential candidates for applications in analytical research, and food- and biotechnology. PMID- 26369953 TI - Growth-rate dependency of de novo resveratrol production in chemostat cultures of an engineered Saccharomyces cerevisiae strain. AB - INTRODUCTION: Saccharomyces cerevisiae has become a popular host for production of non-native compounds. The metabolic pathways involved generally require a net input of energy. To maximize the ATP yield on sugar in S. cerevisiae, industrial cultivation is typically performed in aerobic, sugar-limited fed-batch reactors which, due to constraints in oxygen transfer and cooling capacities, have to be operated at low specific growth rates. Because intracellular levels of key metabolites are growth-rate dependent, slow growth can significantly affect biomass-specific productivity. Using an engineered Saccharomyces cerevisiae strain expressing a heterologous pathway for resveratrol production as a model energy-requiring product, the impact of specific growth rate on yeast physiology and productivity was investigated in aerobic, glucose-limited chemostat cultures. RESULTS: Stoichiometric analysis revealed that de novo resveratrol production from glucose requires 13 moles of ATP per mole of produced resveratrol. The biomass-specific production rate of resveratrol showed a strong positive correlation with the specific growth rate. At low growth rates a substantial fraction of the carbon source was invested in cellular maintenance-energy requirements (e.g. 27 % at 0.03 h(-1)). This distribution of resources was unaffected by resveratrol production. Formation of the by-products coumaric, phloretic and cinnamic acid had no detectable effect on maintenance energy requirement and yeast physiology in chemostat. Expression of the heterologous pathway led to marked differences in transcript levels in the resveratrol producing strain, including increased expression levels of genes involved in pathways for precursor supply (e.g. ARO7 and ARO9 involved in phenylalanine biosynthesis). The observed strong differential expression of many glucose responsive genes in the resveratrol producer as compared to a congenic reference strain could be explained from higher residual glucose concentrations and higher relative growth rates in cultures of the resveratrol producer. CONCLUSIONS: De novo resveratrol production by engineered S. cerevisiae is an energy demanding process. Resveratrol production by an engineered strain exhibited a strong correlation with specific growth rate. Since industrial production in fed-batch reactors typically involves low specific growth rates, this study emphasizes the need for uncoupling growth and product formation via energy-requiring pathways. PMID- 26369954 TI - Australian health care providers' views on opt-out HIV testing. AB - BACKGROUND: Opt-out HIV testing is a novel concept in Australia. In the opt-out approach, health care providers (HCPs) routinely test patients for HIV unless they explicitly decline or defer. Opt-out HIV testing is only performed with the patients' consent, but pre-test counselling is abbreviated. Australian national testing guidelines do not currently recommend opt-out HIV testing for the general population. Non-traditional approaches to HIV testing (such as opt-out) could identify HIV infections and facilitate earlier treatment, which is particularly important now that HIV is a chronic, manageable disease. Our aim was to explore HCPs' attitudes toward opt-out HIV testing in an Australian context, to further understanding of its acceptability and feasibility. METHODS: In this qualitative study, we used purposeful sampling to recruit HCPs who were likely to have experience with HIV testing in Western Australia. We interviewed them using a semi-structured guide and used content analysis as per Graneheim to code the data. Codes were then merged into subcategories and finally themes that unified the underlying concepts. We refined these themes through discussion among the research team. RESULTS: Twenty four HCPs participated. Eleven participants had a questioning attitude toward opt-out HIV testing, while eleven favoured the approach. The remaining two participants had more nuanced perspectives that incorporated some characteristics of the questioning and favouring attitudes. Participants' views about opt-out HIV testing largely fell into two contrasting themes: normalisation and routinisation versus exceptionalism; and a need for proof versus openness to new approaches. CONCLUSION: Most HCPs in this study had dichotomous attitudes toward opt-out HIV testing, reflecting contrasting analytical styles. While some HCPs viewed it favourably, with the perceived benefits outweighing the perceived costs, others preferred to have evidence of efficacy and cost-effectiveness. PMID- 26369955 TI - Nanoscale Plasma Coating Inhibits Formation of Staphylococcus aureus Biofilm. AB - Staphylococcus aureus commonly infects medical implants or devices, with devastating consequences for the patient. The infection begins with bacterial attachment to the device, followed by bacterial multiplication over the surface of the device, generating an adherent sheet of bacteria known as a biofilm. Biofilms resist antimicrobial therapy and promote persistent infection, making management difficult to futile. Infections might be prevented by engineering the surface of the device to discourage bacterial attachment and multiplication; however, progress in this area has been limited. We have developed a novel nanoscale plasma coating technology to inhibit the formation of Staphylococcus aureus biofilms. We used monomeric trimethylsilane (TMS) and oxygen to coat the surfaces of silicone rubber, a material often used in the fabrication of implantable medical devices. By quantitative and qualitative analysis, the TMS/O2 coating significantly decreased the in vitro formation of S. aureus biofilms; it also significantly decreased in vivo biofilm formation in a mouse model of foreign-body infection. Further analysis demonstrated TMS/O2 coating significantly changed the protein adsorption, which could lead to reduced bacterial adhesion and biofilm formation. These results suggest that TMS/O2 coating can be used to effectively prevent medical implant-related infections. PMID- 26369956 TI - In Vitro Activities of Novel Antimicrobial Combinations against Extensively Drug Resistant Acinetobacter baumannii. AB - Extensively drug-resistant (XDR) Acinetobacter spp. have emerged as a cause of nosocomial infections, especially under conditions of intensive care. Unfortunately, resistance to colistin is increasing and there is a need for new therapeutic options. We aimed to study the effect of some novel combinations against XDR Acinetobacter baumannii in an in vitro pharmacokinetics pharmacodynamics (PK/PD) model. Three nonrelated clinical strains of XDR A. baumannii were investigated. Antibiotic-simulated regimens were colistin at 3 MU every 8 h (q8h) (first dose, 6 MU), daptomycin at 10 mg/kg of body weight q24h, imipenem at 1 g q8h, and ertapenem at 1 g q24h. Combination regimens included colistin plus daptomycin, colistin plus imipenem, and imipenem plus ertapenem. Samples were obtained at 0, 1, 2, 4, 8, and 24 h. Among the single-agent regimens, only the colistin regimen resulted in significant reductions in log10 CFU per milliliter compared to the control for all the strains tested. Although colistin achieved bactericidal activity at 4 h, it was not able to reach the limit of detection (1 log10 CFU/ml). One strain had significant regrowth at 24 h without the emergence of resistance. Daptomycin-colistin combinations led to a significant reduction in levels of log10 CFU per milliliter that were better than those achieved with colistin as a single-agent regimen, reaching the limit of detection at 24 h against all the strains. The combination of imipenem plus ertapenem outperformed the colistin regimen, although the results did not reach the limit of detection, with significant regrowth at 24 h. Similarly, colistin plus-imipenem combinations reduced the levels of log10 CFU per milliliter at 8 h, with significant regrowth at 24 h but with development of resistance to colistin. We have shown some potentially useful alternatives for the treatment of extensively drug-resistant A. baumannii. Among them, the daptomycin-colistin combination was the most effective and should be investigated in future studies. PMID- 26369957 TI - Uncoupling Environmental pH and Intrabacterial Acidification from Pyrazinamide Susceptibility in Mycobacterium tuberculosis. AB - Pyrazinamide (PZA) is a first-line antitubercular drug for which the mode of action remains unresolved. Mycobacterium tuberculosis lacks measurable susceptibility to PZA under standard laboratory growth conditions. However, susceptibility to this drug can be induced by cultivation of the bacilli in an acidified growth medium. Previous reports suggested that the active form of PZA, pyrazinoic acid (POA), operates as a proton ionophore that confers cytoplasmic acidification when M. tuberculosis is exposed to an acidic environment. In this study, we demonstrate that overexpression of the PZA-activating enzyme PncA can confer PZA susceptibility to M. tuberculosis under neutral and even alkaline growth conditions. Furthermore, we find that wild-type M. tuberculosis displays increased susceptibility to POA relative to PZA in neutral and alkaline media. Utilizing a strain of M. tuberculosis that expresses a pH-sensitive green fluorescent protein (GFP), we find that unlike the bona fide ionophores monensin and carbonyl cyanide 3-chlorophenylhydrazone, PZA and POA do not induce rapid uncoupling or cytoplasmic acidification under conditions that promote susceptibility. Thus, based on these observations, we conclude that the antitubercular action of POA is independent of environmental pH and intrabacterial acidification. PMID- 26369958 TI - Comparative Effectiveness of Single versus Combination Antibiotic Prophylaxis for Infections after Transrectal Prostate Biopsy. AB - An increase in fluoroquinolone resistance and transrectal ultrasound-guided prostate (TRUS) biopsy infections has prompted the need for alternative effective antibiotic prophylaxis. We aimed to compare ciprofloxacin and other single-agent therapies to combination therapy for efficacy and adverse effects. Men who underwent a TRUS biopsy within the VA Boston health care system with documented receipt of prophylactic antibiotics periprocedure were eligible for inclusion. Postprocedure infections within 30 days were ascertained by chart review from electronic records, including any inpatient, outpatient, or urgent-care visits. Among 455 evaluable men over a 3-year period, there were 25 infections (5.49%), with sepsis occurring in 2.4%, urinary tract infections (UTI) in 1.54%, and bacteremia in 0.44% of patients. Escherichia coli was the most common urine (89%) and blood (92%) pathogen, with fluoroquinolone resistance rates of 88% and 91%, respectively. Ciprofloxacin alone was associated with significantly more infections than ciprofloxacin plus an additional agent (P = 0.014). Intramuscular gentamicin alone was also significantly associated with a higher infection rate obtained with all other regimens (P = 0.004). Any single-agent regimen, including ciprofloxacin, ceftriaxone, or gentamicin, was associated with significantly higher infection rates than any combination regimen (odds ratio [OR], 4; 95% confidence interval [CI], 1.47, 10.85; P = 0.004). Diabetes, immunosuppressive condition or medication, hospitalization within the previous year, and UTI within the previous 6 months were not associated with infection risk. Clostridium difficile infections were similar. These findings suggest that ciprofloxacin, ceftriaxone, and gentamicin alone are inferior to a combination regimen. Institutions with high failure rates of prophylaxis for TRUS biopsies should consider combination regimens derived from their local data. PMID- 26369959 TI - Deletion of liaR Reverses Daptomycin Resistance in Enterococcus faecium Independent of the Genetic Background. AB - We have shown previously that changes in LiaFSR, a three-component regulatory system predicted to orchestrate the cell membrane stress response, are important mediators of daptomycin (DAP) resistance in enterococci. Indeed, deletion of the gene encoding the response regulator LiaR in a clinical strain of Enterococcus faecalis reversed DAP resistance (DAP-R) and produced a strain hypersusceptible to antimicrobial peptides. Since LiaFSR is conserved in Enterococcus faecium, we investigated the role of LiaR in a variety of clinical E. faecium strains representing the most common DAP-R genetic backgrounds. Deletion of liaR in DAP-R E. faecium R446F (DAP MIC of 16 MUg/ml) and R497F (MIC of 24 MUg/ml; harboring changes in LiaRS) strains fully reversed resistance (DAP MICs decreasing to 0.25 and 0.094 MUg/ml, respectively). Moreover, DAP at concentrations of 13 MUg/ml (achieved with human doses of 12 mg/kg body weight) retained bactericidal activity against the mutants. Furthermore, the liaR deletion derivatives of these two DAP-R strains exhibited increased binding of boron-dipyrromethene difluoride (BODIPY)-daptomycin, suggesting that high-level DAP-R mediated by LiaR in E. faecium involves repulsion of the calcium-DAP complex from the cell surface. In DAP-tolerant strains HOU503F and HOU515F (DAP MICs within the susceptible range but bacteria not killed by DAP concentrations of 5* the MIC), deletion of liaR not only markedly decreased the DAP MICs (0.064 and 0.047 MUg/ml, respectively) but also restored the bactericidal activity of DAP at concentrations as low as 4 MUg/ml (achieved with human doses of 4 mg/kg). Our results suggest that LiaR plays a relevant role in the enterococcal cell membrane adaptive response to antimicrobial peptides independent of the genetic background and emerges as an attractive target to restore the activity of DAP against multidrug-resistant strains. PMID- 26369960 TI - Elucidating the Role of Residue 67 in IMP-Type Metallo-beta-Lactamase Evolution. AB - Antibiotic resistance in bacteria is ever changing and adapting, as once-novel beta-lactam antibiotics are losing their efficacy, primarily due to the production of beta-lactamases. Metallo-beta-lactamases (MBLs) efficiently inactivate a broad range of beta-lactam antibiotics, including carbapenems, and are often coexpressed with other antibacterial resistance factors. The rapid dissemination of MBLs and lack of novel antibacterials pose an imminent threat to global health. In an effort to better counter these resistance-conferring beta lactamases, an investigation of their natural evolution and resulting substrate specificity was employed. In this study, we elucidated the effects of different amino acid substitutions at position 67 in IMP-type MBLs on the ability to hydrolyze and confer resistance to a range of beta-lactam antibiotics. Wild-type beta-lactamases IMP-1 and IMP-10 and mutants IMP-1-V67A and IMP-1-V67I were characterized biophysically and biochemically, and MICs for Escherichia coli cells expressing these enzymes were determined. We found that all variants exhibited catalytic efficiencies (kcat/Km) equal to or higher than that of IMP-1 against all tested beta-lactams except penicillins, against which IMP-1 and IMP-1 V67I showed the highest kcat/Km values. The substrate-specific effects of the different amino acid substitutions at position 67 are discussed in light of their side chain structures and possible interactions with the substrates. Docking calculations were employed to investigate interactions between different side chains and an inhibitor used as a beta-lactam surrogate. The differences in binding affinities determined experimentally and computationally seem to be governed by hydrophobic interactions between residue 67 and the inhibitor and, by inference, the beta-lactam substrates. PMID- 26369961 TI - Antibiotic Selection Pressure Determination through Sequence-Based Metagenomics. AB - The human gut forms a dynamic reservoir of antibiotic resistance genes (ARGs). Treatment with antimicrobial agents has a significant impact on the intestinal resistome and leads to enhanced horizontal transfer and selection of resistance. We have monitored the development of intestinal ARGs over a 6-day course of ciprofloxacin (Cp) treatment in two healthy individuals by using sequenced-based metagenomics and different ARG quantification methods. Fixed- and random-effect models were applied to determine the change in ARG abundance per defined daily dose of Cp as an expression of the respective selection pressure. Among various shifts in the composition of the intestinal resistome, we found in one individual a strong positive selection for class D beta-lactamases which were partly located on a mobile genetic element. Furthermore, a trend to a negative selection has been observed with class A beta-lactamases (-2.66 hits per million sample reads/defined daily dose; P = 0.06). By 4 weeks after the end of treatment, the composition of ARGs returned toward their initial state but to a different degree in both subjects. We present here a novel analysis algorithm for the determination of antibiotic selection pressure which can be applied in clinical settings to compare therapeutic regimens regarding their effect on the intestinal resistome. This information is of critical importance for clinicians to choose antimicrobial agents with a low selective force on their patients' intestinal ARGs, likely resulting in a diminished spread of resistance and a reduced burden of hospital-acquired infections with multidrug-resistant pathogens. PMID- 26369962 TI - Activation of Antibiotic Production in Bacillus spp. by Cumulative Drug Resistance Mutations. AB - Bacillus subtilis strains produce a wide range of antibiotics, including ribosomal and nonribosomal peptide antibiotics, as well as bacilysocin and neotrehalosadiamine. Mutations in B. subtilis strain 168 that conferred resistance to drugs such as streptomycin and rifampin resulted in overproduction of the dipeptide antibiotic bacilysin. Cumulative drug resistance mutations, such as mutations in the mthA and rpsL genes, which confer low- and high-level resistance, respectively, to streptomycin, and mutations in rpoB, which confer resistance to rifampin, resulted in cells that overproduced bacilysin. Transcriptional analysis demonstrated that the enhanced transcription of biosynthesis genes was responsible for the overproduction of bacilysin. This approach was effective also in activating the cryptic genes of Bacillus amyloliquefaciens, leading to actual production of antibiotic(s). PMID- 26369963 TI - Observed Antagonistic Effect of Linezolid on Daptomycin or Vancomycin Activity against Biofilm-Forming Methicillin-Resistant Staphylococcus aureus in an In Vitro Pharmacodynamic Model. AB - Pharmacodynamic activity in antibiotic combinations of daptomycin, vancomycin, and linezolid was investigated in a 48-h in vitro pharmacodynamic model. Using human-simulated free drug concentrations, activity against clinical biofilm forming methicillin-resistant Staphylococcus aureus isolates was evaluated. Linezolid antagonized vancomycin activity at 24 and 48 h. Linezolid antagonized daptomycin at 24 and 48 h depending on dose and strain. Adding daptomycin increased vancomycin activity at 48 h (P < 0.03). These results may be strain dependent and require further clinical investigation. PMID- 26369964 TI - Evaluation of VT-1161 for Treatment of Coccidioidomycosis in Murine Infection Models. AB - Coccidioidomycosis, or valley fever, is a growing health concern endemic to the southwestern United States. Safer, more effective, and more easily administered drugs are needed especially for severe, chronic, or unresponsive infections. The novel fungal CYP51 inhibitor VT-1161 demonstrated in vitro antifungal activity, with MIC50 and MIC90 values of 1 and 2 MUg/ml, respectively, against 52 Coccidioides clinical isolates. In the initial animal study, oral doses of 10 and 50 mg/kg VT-1161 significantly reduced fungal burdens and increased survival time in a lethal respiratory model in comparison with treatment with a placebo (P < 0.001). Oral doses of 25 and 50 mg/kg VT-1161 were similarly efficacious in the murine central nervous system (CNS) model compared to placebo treatment (P < 0.001). All comparisons with the positive-control drug, fluconazole at 50 mg/kg per day, demonstrated either statistical equivalence or superiority of VT-1161. VT-1161 treatment also prevented dissemination of infection from the original inoculation site to a greater extent than fluconazole. Many of these in vivo results can be explained by the long half-life of VT-1161 leading to sustained high plasma levels. Thus, the efficacy and pharmacokinetics of VT-1161 are attractive characteristics for long-term treatment of this serious fungal infection. PMID- 26369965 TI - Genotypic Analysis of Genes Associated with Independent Resistance and Cross Resistance to Isoniazid and Ethionamide in Mycobacterium tuberculosis Clinical Isolates. AB - Ethionamide (ETH) is an antibiotic used for the treatment of multidrug-resistant (MDR) tuberculosis (TB) (MDR-TB), and its use may be limited with the emergence of resistance in the Mycobacterium tuberculosis population. ETH resistance in M. tuberculosis is phenomenon independent or cross related when accompanied with isoniazid (INH) resistance. In most cases, resistance to INH and ETH is explained by mutations in the inhA promoter and in the following genes: katG, ethA, ethR, mshA, ndh, and inhA. We sequenced the above genes in 64 M. tuberculosis isolates (n = 57 ETH-resistant MDR-TB isolates; n = 3 ETH-susceptible MDR-TB isolates; and n = 4 fully susceptible isolates). Each isolate was tested for susceptibility to first- and second-line drugs using the agar proportion method. Mutations were observed in ETH-resistant MDR-TB isolates at the following rates: 100% in katG, 72% in ethA, 45.6% in mshA, 8.7% in ndh, and 33.3% in inhA or its promoter. Of the three ETH-susceptible MDR-TB isolates, all showed mutations in katG; one had a mutation in ethA, and another, in mshA and inhA. Finally, of the four fully susceptible isolates, two showed no detectable mutation in the studied genes, and two had mutations in mshA gene unrelated to the resistance. Mutations not previously reported were found in the ethA, mshA, katG, and ndh genes. The concordance between the phenotypic susceptibility testing to INH and ETH and the sequencing was 1 and 0.45, respectively. Among isolates exhibiting INH resistance, the high frequency of independent resistance and cross-resistance with ETH in the M. tuberculosis isolates suggests the need to confirm the susceptibility to ETH before considering it in the treatment of patients with MDR TB. PMID- 26369966 TI - High Prevalence of vanM in Vancomycin-Resistant Enterococcus faecium Isolates from Shanghai, China. AB - The vanM gene was first found in a vancomycin-resistant Enterococcus faecium (VREm) isolate in Shanghai in 2006. In this study, we found that, in 70 VREm strains isolated in nine Shanghai hospitals from 2006 to 2014, vanM was more prevalent than the vanA gene (64.3% [45/70] versus 35.7% [25/70]). The vanM-type isolates showed similar antimicrobial susceptibility patterns with the vanA types. The vanM-type VREm emerged and disseminated in Shanghai. PMID- 26369967 TI - Griffithsin and Carrageenan Combination To Target Herpes Simplex Virus 2 and Human Papillomavirus. AB - Extensive preclinical evaluation of griffithsin (GRFT) has identified this lectin to be a promising broad-spectrum microbicide. We set out to explore the antiviral properties of a GRFT and carrageenan (CG) combination product against herpes simplex virus 2 (HSV-2) and human papillomavirus (HPV) as well as determine the mechanism of action (MOA) of GRFT against both viruses. We performed the experiments in different cell lines, using time-of-addition and temperature dependence experiments to differentiate inhibition of viral attachment from entry and viral receptor internalization. Surface plasmon resonance (SPR) was used to assess GRFT binding to viral glycoproteins, and immunoprecipitation and immunohistochemistry were used to identify the specific glycoprotein involved. We determined the antiviral activity of GRFT against HSV-2 to be a 50% effective concentration (EC50) of 230 nM and provide the first evidence that GRFT has moderate anti-HPV activity (EC50 = 0.429 to 1.39 MUM). GRFT blocks the entry of HSV-2 and HPV into target cells but not the adsorption of HSV-2 and HPV onto target cells. The results of the SPR, immunoprecipitation, and immunohistochemistry analyses of HSV-2 combined suggest that GRFT may block viral entry by binding to HSV-2 glycoprotein D. Cell-based assays suggest anti-HPV activity through alpha6 integrin internalization. The GRFT-CG combination product but not GRFT or CG alone reduced HSV-2 vaginal infection in mice when given an hour before challenge (P = 0.0352). While GRFT significantly protected mice against vaginal HPV infection when dosed during and after HPV16 pseudovirus challenge (P < 0.026), greater CG-mediated protection was afforded by the GRFT-CG combination for up to 8 h (P < 0.0022). These findings support the development of the GRFT-CG combination as a broad-spectrum microbicide. PMID- 26369968 TI - Thymidine-Dependent Staphylococcus aureus Small-Colony Variants Are Induced by Trimethoprim-Sulfamethoxazole (SXT) and Have Increased Fitness during SXT Challenge. AB - Trimethoprim-sulfamethoxazole (SXT) is a possible alternative for the treatment of community- and hospital-acquired methicillin-resistant Staphylococcus aureus (MRSA) due to the susceptibility of most MRSA strains to the drug. However, after long-term treatment with SXT, thymidine-dependent (TD) SXT-resistant small-colony variants (SCVs) emerge. In TD-SCVs, mutations of thymidylate synthase ([TS] thyA) occur. Until now, it has never been systematically investigated that SXT is triggering the induction and/or selection of TD-SCVs. In our study, we performed induction, reversion, and competition experiments in vitro and in vivo using a chronic mouse pneumonia model to determine the impact of SXT on the emergence of TD-SCVs. SCVs were characterized by light and transmission electron microscopy (TEM) and auxotrophism testing. Short-term exposure of S. aureus to SXT induced the TD-SCV phenotype in S. aureus SH1000, while selection of TD-SCVs with thyA mutations occurred after long-term exposure. In reversion experiments with clinical and laboratory TD-SCVs, all revertants carried compensating mutations at the initially identified mutation site. Competition experiments in vitro and in vivo revealed a survival and growth advantage of the DeltathyA mutant under low thymidine availability and SXT exposure although this advantage was less profound in vivo. Our results show that SXT induces the TD-SCV phenotype after short-term exposure, while long-term exposure selects for thyA mutations, which provide an advantage for TD-SCVs under specified conditions. Thus, our results further an understanding of the dynamic processes occurring during SXT exposure with induction and selection of S. aureus TD-SCVs. PMID- 26369969 TI - Assessment of Antiviral Properties of Peramivir against H7N9 Avian Influenza Virus in an Experimental Mouse Model. AB - The H7N9 influenza virus causes a severe form of disease in humans. Neuraminidase inhibitors, including oral oseltamivir and injectable peramivir, are the first choices of antiviral treatment for such cases; however, the clinical efficacy of these drugs is questionable. Animal experimental models are essential for understanding the viral replication kinetics under the selective pressure of antiviral agents. This study demonstrates the antiviral activity of peramivir in a mouse model of H7N9 avian influenza virus infection. The data show that repeated administration of peramivir at 30 mg/kg of body weight successfully eradicated the virus from the respiratory tract and extrapulmonary tissues during the acute response, prevented clinical signs of the disease, including neuropathy, and eventually protected mice against lethal H7N9 influenza virus infection. Early treatment with peramivir was found to be associated with better disease outcomes. PMID- 26369970 TI - Polymyxin Susceptibility in Pseudomonas aeruginosa Linked to the MexXY-OprM Multidrug Efflux System. AB - The ribosome-targeting antimicrobial, spectinomycin (SPC), strongly induced the mexXY genes of the MexXY-OprM multidrug efflux system in Pseudomonas aeruginosa and increased susceptibility to the polycationic antimicrobials polymyxin B and polymyxin E, concomitant with a decrease in expression of the polymyxin resistance-promoting lipopolysaccharide (LPS) modification loci, arnBCADTEF and PA4773-74. Consistent with the SPC-promoted reduction in arn and PA4773-74 expression being linked to mexXY, expression of these LPS modification loci was moderated in a mutant constitutively expressing mexXY and enhanced in a mutant lacking the efflux genes. Still, the SPC-mediated increase in polymyxin susceptibility was retained in mutants lacking arnB and/or PA4773-74, an indication that their reduced expression in SPC-treated cells does not explain the enhanced polymyxin susceptibility. That the polymyxin susceptibility of a mutant strain lacking mexXY was unaffected by SPC exposure, however, was an indication that the unknown polymyxin resistance 'mechanism' is also influenced by the MexXY status of the cell. In agreement with SPC and MexXY influencing polymyxin susceptibility as a result of changes in the LPS target of these agents, SPC treatment yielded a decline in common polysaccharide antigen (CPA) synthesis in wild-type P. aeruginosa but not in the DeltamexXY mutant. A mutant lacking CPA still showed the SPC-mediated decline in polymyxin MICs, however, indicating that the loss of CPA did not explain the SPC-mediated MexXY-dependent increase in polymyxin susceptibility. It is possible, therefore, that some additional change in LPS promoted by SPC-induced mexXY expression impacted CPA synthesis or its incorporation into LPS and that this was responsible for the observed changes in polymyxin susceptibility. PMID- 26369971 TI - Acinetobacter baumannii Extracellular OXA-58 Is Primarily and Selectively Released via Outer Membrane Vesicles after Sec-Dependent Periplasmic Translocation. AB - Carbapenem-resistant Acinetobacter baumannii (CRAb) shelter cohabiting carbapenem susceptible bacteria from carbapenem killing via extracellular release of carbapenem-hydrolyzing class D beta-lactamases, including OXA-58. However, the mechanism of the extracellular release of OXA-58 has not been elucidated. In silico analysis predicted OXA-58 to be translocated to the periplasm via the Sec system. Using cell fractionation and Western blotting, OXA-58 with the signal peptide and C terminus deleted was not detected in the periplasmic and extracellular fractions. Overexpression of enhanced green fluorescent protein fused to the OXA-58 signal peptide led to its periplasmic translocation but not extracellular release, suggesting that OXA-58 is selectively released. The majority of the extracellular OXA-58 was associated with outer membrane vesicles (OMVs). The OMV-associated OXA-58 was detected only in a strain overexpressing OXA-58. The presence of OXA-58 in OMVs was confirmed by a carbapenem inactivation bioassay, proteomic analysis, and transmission electron microscopy. Imipenem treatment increased OMV formation and caused cell lysis, resulting in an increase in the OMV-associated and OMV-independent release of extracellular OXA-58. OMV independent OXA-58 hydrolyzed nitrocefin more rapidly than OMV-associated OXA-58 but was more susceptible to proteinase K degradation. Rose bengal, an SecA inhibitor, inhibited the periplasmic translocation and OMV-associated release of OXA-58 and abolished the sheltering effect of CRAb. This study demonstrated that the majority of the extracellular OXA-58 is selectively released via OMVs after Sec-dependent periplasmic translocation. Addition of imipenem increased both OMV associated and OMV-independent OXA-58, which may have different biological roles. SecA inhibitor could abolish the carbapenem-sheltering effect of CRAb. PMID- 26369972 TI - Antiviral Activity of Broad-Spectrum and Enterovirus-Specific Inhibitors against Clinical Isolates of Enterovirus D68. AB - We investigated the susceptibility of 10 enterovirus D68 (EV-D68) isolates (belonging to clusters A, B, and C) to (entero)virus inhibitors with different mechanisms of action. The 3C-protease inhibitors proved to be more efficient than enviroxime and pleconaril, which in turn were more effective than vapendavir and pirodavir. Favipiravir proved to be a weak inhibitor. Resistance to pleconaril maps to V69A in the VP1 protein, and resistance to rupintrivir maps to V104I in the 3C protease. A structural explanation of why both substitutions may cause resistance is provided. PMID- 26369973 TI - Outcomes of Aminopenicillin Therapy for Vancomycin-Resistant Enterococcal Urinary Tract Infections. AB - Vancomycin-resistant urinary tract infections are often challenging to treat. This retrospective cohort study compared outcomes between patients treated for vancomycin-resistant enterococcal urinary tract infection with an aminopenicillin and those treated with a non-beta-lactam antibiotic. Inpatients treated with an enterococcus-active agent for their first symptomatic vancomycin-resistant enterococcal urinary tract infection between 1 January 2012 and 31 December 2013 were considered for inclusion. Patients with colonization, on hospice, or receiving comfort care only were excluded. The primary endpoint of clinical cure was defined as resolution of clinical symptoms, or symptom improvement to the extent that no additional antibacterial drug therapy was necessary, and lack of microbiologic persistence. Secondary endpoints of 30-day readmission or retreatment and 30-day all-cause mortality were also compared. A total of 316 urinary isolates were screened, and 61 patients with symptomatic urinary tract infection were included. Twenty (35%) of the 57 isolates tested were ampicillin susceptible. Thirty-one patients received an aminopenicillin, and 30 received a non-beta-lactam. Rates of clinical cure for aminopenicillin versus non-beta lactam treatment were 26/31 (83.9%) and 22/30 (73.3%) (P = 0.315), respectively. Rates of 30-day readmission (6/31, or 19.4%, versus 9/30, or 30%, respectively; P = 0.334), 30-day retreatment (4/31, or 12.9%, versus 4/30, 13.3%, respectively; P = 0.960), and 30-day all-cause mortality (2/31, or 6.5%, versus 1/30, or 3.3%, respectively; P = 0.573) were also not significantly different between groups. Aminopenicillins may be a viable option for treating vancomycin-resistant urinary tract infection regardless of the organism's ampicillin susceptibility. Prospective validation with larger cohorts of patients should be considered. PMID- 26369974 TI - Colistin Population Pharmacokinetics after Application of a Loading Dose of 9 MU Colistin Methanesulfonate in Critically Ill Patients. AB - Colistin has been revived, in the era of extensively drug-resistant (XDR) Gram negative infections, as the last-resort treatment in critically ill patients. Recent studies focusing on the optimal dosing strategy of colistin have demonstrated the necessity of a loading dose at treatment initiation (D. Plachouras, M. Karvanen, L. E. Friberg, E. Papadomichelakis, A. Antoniadou, I. Tsangaris, I. Karaiskos, G. Poulakou, F. Kontopidou, A. Armaganidis, O. Cars, and H. Giamarellou, Antimicrob Agents Chemother 53:3430-3436, 2009, http://dx.doi.org/10.1128/AAC.01361-08; A. F. Mohamed, I. Karaiskos, D. Plachouras, M. Karvanen, K. Pontikis, B. Jansson, E. Papadomichelakis, A. Antoniadou, H. Giamarellou, A. Armaganidis, O. Cars, and L. E. Friberg, Antimicrob Agents Chemother 56:4241- 4249, 2012, http://dx.doi.org/10.1128/AAC.06426-11; S. M. Garonzik, J. Li, V. Thamlikitkul, D. L. Paterson, S. Shoham, J. Jacob, F. P. Silveira, A. Forrest, and R. L. Nation, Antimicrob Agents Chemother 55:3284-3294, 2011, http://dx.doi.org/10.1128/AAC.01733-10). In 19 critically ill patients with suspected or microbiologically documented infections caused by XDR Gram-negative strains, a loading dose of 9 MU colistin methanesulfonate (CMS) (~ 270 mg colistin base activity) was administered with a maintenance dose of 4.5 MU every 12 h, commenced after 24 h. Patients on renal replacement were excluded. CMS infusion was given over 30 min or 1 h. Repeated blood sampling was performed after the loading dose and after the 5th or 6th dose. Colistin concentrations and measured CMS, determined after hydrolization to colistin and including the partially sulfomethylated derivatives, were determined with a liquid chromatography-tandem mass spectrometry assay. Population pharmacokinetic analysis was conducted in NONMEM with the new data combined with data from previous studies. Measured colistimethate concentrations were described by 4 compartments for distribution and removal of sulfomethyl groups, while colistin disposition followed a 1-compartment model. The average observed maximum colistin A plus B concentration was 2.65 mg/liter after the loading dose (maximum time was 8 h). A significantly higher availability of the measured A and B forms of colistimethate and colistin explained the higher-than-expected concentrations in the present study compared to those in previous studies. Creatinine clearance was a time-varying covariate of colistimethate clearance. The incidence of acute renal injury was 20%. PMID- 26369975 TI - Biochemical Characterization of VIM-39, a VIM-1-Like Metallo-beta-Lactamase Variant from a Multidrug-Resistant Klebsiella pneumoniae Isolate from Greece. AB - VIM-39, a VIM-1-like metallo-beta-lactamase variant (VIM-1 Thr33Ala His224Leu) was identified in a clinical isolate of Klebsiella pneumoniae belonging to sequence type 147. VIM-39 hydrolyzed ampicillin, cephalothin, and imipenem more efficiently than did VIM-1 and VIM-26 (a VIM-1 variant with the His224Leu substitution) because of higher turnover rates. PMID- 26369976 TI - In Vitro Susceptibility Profiles of Eight Antifungal Drugs against Clinical and Environmental Strains of Phaeoacremonium. AB - In vitro susceptibilities of a worldwide collection of molecularly identified Phaeoacremonium strains (n = 43) belonging to seven species and originating from human and environmental sources were determined for eight antifungal drugs. Voriconazole had the lowest geometric mean MIC (0.35 MUg/ml), followed by posaconazole (0.37 MUg/ml), amphotericin B (0.4 MUg/ml), and isavuconazole (1.16 MUg/ml). Caspofungin, anidulafungin, fluconazole, and itraconazole had no activity. PMID- 26369977 TI - VT-1161 Protects Immunosuppressed Mice from Rhizopus arrhizus var. arrhizus Infection. AB - We studied the efficacy of the investigational drug VT-1161 against mucormycosis. VT-1161 had more potent in vitro activity against Rhizopus arrhizus var. arrhizus than against R. arrhizus var. delemar. VT-1161 treatment demonstrated dose dependent plasma drug levels with prolonged survival time and lowered tissue fungal burden in immunosuppressed mice infected with R. arrhizus var. arrhizus and was as effective as high-dose liposomal amphotericin B treatment. These results support further development of VT-1161 against mucormycosis. PMID- 26369978 TI - Clinical Appraisal of Fosfomycin in the Era of Antimicrobial Resistance. AB - Fosfomycin is recommended as one of the first-line agents for treatment of urinary tract infections (UTIs) in the latest guidelines endorsed by the Infectious Diseases Society of America (IDSA) and the European Society for Clinical Microbiology and Infectious Diseases (ESCMID). We evaluated the use of fosfomycin among inpatients at a tertiary care hospital between 2009 and 2013. UTI cases were defined using physician diagnosis and the National Healthcare Safety Network (NHSN) surveillance definitions. The number of patients treated with fosfomycin increased from none in 2009 to 391 in 2013. Among 537 patients who received fosfomycin for any indication during this period, UTI was the most common indication (74%), followed by asymptomatic bacteriuria (10%). All except 19 patients received a single dose of fosfomycin. Escherichia coli was the most common organism involved (52%). For 119 patients with UTIs, after exclusion of those with negative urine culture results, negative urinalysis results, receipt of additional agents, or indeterminate clinical outcomes, the clinical success rate at 48 h was 74.8%. Of 89 patients who met the criteria for NHSN-defined UTIs, 89.9% had successful outcomes. Recurrent infections occurred in 4.3% of cases, and mild adverse events were observed in 2.0%. All 100 randomly selected extended-spectrum beta-lactamase (ESBL)-producing E. coli clinical isolates from this period were susceptible to fosfomycin. In conclusion, the use of fosfomycin has increased substantially since implementation of the updated guidelines at this hospital. Fosfomycin was used mainly for the treatment of physician diagnosed UTIs, and the clinical outcomes were generally favorable. Fosfomycin maintained activity against E. coli despite the increased use of the agent. PMID- 26369979 TI - Treatment of Experimental Candida Sepsis with a Janus Kinase Inhibitor Controls Inflammation and Prolongs Survival. AB - Janus kinases (JAK) are intracellular tyrosine kinases that transduce cytokine mediated signals to the nucleus, promoting gene expression. Cytokines play a major role in microbial sepsis, which is often associated with uncontrolled inflammation leading to death. JAK inhibitors have been used for the treatment of several autoimmune diseases by modulating immune response, but they have never been tested against microbial sepsis. Ruxolitinib is a small-molecule inhibitor of JAK1/2 proteins, which are involved in the downstream signaling pathway of the vast majority of proinflammatory and anti-inflammatory cytokines. We therefore studied the effect of ruxolitinib in a mouse model of sepsis due to Candida albicans. When ruxolitinib therapy (50 mg/kg [of body weight]/day) was started 1 day before infection, the median survival time was reduced by 3 days, the fungal loads in all organs were higher, the inflammation was significantly less, and serum tumor necrosis factor alpha (TNF-alpha) and interleukin 10 (IL-10) levels and IL-10/TNF-alpha ratios were higher than in controls. When ruxolitinib therapy (50 to 1.5 mg/kg/day) was started 1 day after infection, an inverted-U relationship was found, with 6.25 mg/kg/day prolonging median survival time by 6 days, resulting in similar fungal loads, less inflammation, and similar cytokine levels but higher IL-10/TNF-alpha ratios than the controls. The optimal dose of ruxolitinib controlled infection and prolonged survival with less inflammation than in control animals. Administration of JAK inhibitors may be a promising therapeutic adjunct that needs further investigation. PMID- 26369980 TI - Distribution of Cenozoic plant relicts in China explained by drought in dry season. AB - Cenozoic plant relicts are those groups that were once widespread in the Northern Hemisphere but are now restricted to some small isolated areas as a result of drastic climatic changes. They are good proxies to study how plants respond to climatic changes since their modern climatic requirements are known. Herein we look at the modern distribution of 65 palaeoendemic genera in China and compare it with the Chinese climatic pattern, in order to find a link between the plant distribution and climate. Central China and Taiwan Island are shown to be diversity centres of Cenozoic relict genera, consistent with the fact that these two regions have a shorter dry season with comparatively humid autumn and spring in China. Species distribution models indicate that the precipitation parameters are the most important variables to explain the distribution of relict genera. The Cenozoic wide-scale distribution of relict plants in the Northern Hemisphere is therefore considered to be linked to the widespread humid climate at that time, and the subsequent contraction of their distributional ranges was probably caused by the drying trend along with global cooling. PMID- 26369981 TI - Unrelated cord blood transplantation for childhood acute myelogenous leukemia: The influence of cytogenetic risk group stratification. PMID- 26369982 TI - Comprehensive quantitative proteomic profiling of the pharmacodynamic changes induced by MLN4924 in acute myeloid leukemia cells establishes rationale for its combination with azacitidine. PMID- 26369983 TI - Presence of polyclonal hematopoiesis in females with Ph-negative myeloproliferative neoplasms. PMID- 26369984 TI - Outcome of relapsed infant acute lymphoblastic leukemia treated on the interfant 99 protocol. PMID- 26369985 TI - Risk factors for second acute myeloid leukemia/myelodysplastic syndrome among survivors of non-Hodgkin lymphoma. PMID- 26369986 TI - Telomere length at diagnosis of chronic phase chronic myeloid leukemia (CML-CP) identifies a subgroup with favourable prognostic parameters and molecular response according to the ELN criteria after 12 months of treatment with nilotinib. PMID- 26369988 TI - Effect of the Thermal Conductivity on Resistive Switching in GeTe and Ge2Sb2Te5 Nanowires. AB - The thermal conduction characteristics of GeTe and Ge2Sb2Te5(GST) nanowires were investigated using an optical method to determine the local temperature by Raman spectroscopy. Since the localization of surface charge in a single-crystalline nanostructure can enhance charge-phonon scattering, the thermal conductivity value (kappa) of single crystalline GeTe and GST nanowires was decreased significantly to 1.44 Wm(-1) K(-1) for GeTe and 1.13 Wm(-1) K(-1) for GST, compared to reported values for polycrystalline structures. The SET-to-RESET state in single-crystalline GeTe and GST nanowires are characteristic of a memory device. Unlike previous reports using GeTe and GST nanowires, the SET-to-RESET characteristics showed a bipolar switching shape and no unipolar switching. In addition, after multiple cycles of operation, a significant change in morphology and composition was observed without any structural phase transition, indicating that atoms migrate toward the cathode or anode, depending on their electronegativities. This change caused by a field effect indicates that the structural phase transition does not occur in the case of GeTe and GST nanowires with a significantly lowered thermal conductivity and stable crystalline structure. Finally, the formation of voids and hillocks as the result of the electromigration critically degrades device reliability. PMID- 26369987 TI - Chimeric antigen receptor-modified T cells derived from defined CD8+ and CD4+ subsets confer superior antitumor reactivity in vivo. AB - Adoptive T-cell therapy with gene-modified T cells expressing a tumor-reactive T cell receptor or chimeric antigen receptor (CAR) is a rapidly growing field of translational medicine and has shown success in the treatment of B-cell malignancies and solid tumors. In all reported trials, patients have received T cell products comprising random compositions of CD4(+) and CD8(+) naive and memory T cells, meaning that each patient received a different therapeutic agent. This variation may have influenced the efficacy of T-cell therapy, and complicates comparison of outcomes between different patients and across trials. We analyzed CD19 CAR-expressing effector T cells derived from different subsets (CD4(+)/CD8(+) naive, central memory, effector memory). T cells derived from each of the subsets were efficiently transduced and expanded, but showed clear differences in effector function and proliferation in vitro and in vivo. Combining the most potent CD4(+) and CD8(+) CAR-expressing subsets, resulted in synergistic antitumor effects in vivo. We show that CAR-T-cell products generated from defined T-cell subsets can provide uniform potency compared with products derived from unselected T cells that vary in phenotypic composition. These findings have important implications for the formulation of T-cell products for adoptive therapies. PMID- 26369989 TI - Central nervous system abnormalities in Fanconi anaemia: patterns and frequency on magnetic resonance imaging. AB - OBJECTIVE: Fanconi anaemia (FA) is an inherited disease associated with congenital and developmental abnormalities resulting from the disruption of a multigenic DNA damage response pathway. This study aimed to define the MRI appearances of the brain in patients with FA in correlation with their genetic and clinical features. METHODS: A review of the brain MRI in 20 patients with FA was performed. Pituitary size and frequencies of the radiological findings of individuals with FA and age-matched controls were determined. RESULTS: Abnormalities were identified in 18 (90%) patients with FA, the commonest being a small pituitary (68%, p < 0.01 females and p < 0.001 males). In five cases (25%, p = 0.02), the pituitary morphology was also abnormal. Posterior fossa abnormalities were seen in six cases (30%, p = 0.01) including Chiari I malformation (n = 3), Dandy-Walker variant (n = 2) and cerebellar atrophy (n = 2). Six patients (30%, p = 0.01) had morphological structural variation of the corpus callosum (CC). CONCLUSION: The incidence of central nervous system (CNS) abnormalities in FA is higher than previously reported, with a midline predominance that points to impact in the early stages of CNS development. MRI brain imaging is important for endocrine assessment and pre-transplant evaluation and can make an important contribution to clinical decision-making. ADVANCES IN KNOWLEDGE: The incidence of brain structural abnormalities in FA is higher than previously reported, with abnormalities of the posterior fossa, CC and pituitary being common. There is an association with gender and reduction in pituitary size which does not strongly correlate with biochemically evident endocrine abnormality. PMID- 26369990 TI - The glucocorticoid mometasone furoate is a novel FXR ligand that decreases inflammatory but not metabolic gene expression. AB - The Farnesoid X receptor (FXR) regulates bile salt, glucose and cholesterol homeostasis by binding to DNA response elements, thereby activating gene expression (direct transactivation). FXR also inhibits the immune response via tethering to NF-kappaB (tethering transrepression). FXR activation therefore has therapeutic potential for liver and intestinal inflammatory diseases. We aim to identify and develop gene-selective FXR modulators, which repress inflammation, but do not interfere with its metabolic capacity. In a high-throughput reporter based screen, mometasone furoate (MF) was identified as a compound that reduced NF-kappaB reporter activity in an FXR-dependent manner. MF reduced mRNA expression of pro-inflammatory cytokines, and induction of direct FXR target genes in HepG2-GFP-FXR cells and intestinal organoids was minor. Computational studies disclosed three putative binding modes of the compound within the ligand binding domain of the receptor. Interestingly, mutation of W469A residue within the FXR ligand binding domain abrogated the decrease in NF-kappaB activity. Finally, we show that MF-bound FXR inhibits NF-kappaB subunit p65 recruitment to the DNA of pro-inflammatory genes CXCL2 and IL8. Although MF is not suitable as selective anti-inflammatory FXR ligand due to nanomolar affinity for the glucocorticoid receptor, we show that separation between metabolic and anti inflammatory functions of FXR can be achieved. PMID- 26369991 TI - Hysteroscopic treatment of uterine tumor resembling ovarian sex cord-like tumor (UTROSCT). AB - The decision to preserve the uterus in a young nulliparous woman with an extremely rare tumor is challenging. Uterine tumor resembling ovarian sex cord like tumor (UTROSCT) belongs to the rarest uterine pathologies. A 22-year-old nulligravida with uterine bleeding underwent a hysteroscopic resection of an intrauterine mass presumed as grade-1 submucous myoma. According to the presence of sex cord-like differentiation and positivity for calretinin, CD99, estrogen receptor, vimentin, WT1 and Melan-A, the tumor was diagnosed as UTROSCT. After 28 months, without any adjuvant therapy, the patient is still free of recurrence. This is the youngest patient with UTROSCT reported so far, with the longest follow-up among all five cases treated via hysteroscopy. Although UTROSCT has been traditionally treated with hysterectomy (with or without bilateral salpingo oophorectomy), no established treatment protocol for UTROSCT exists. UTROSCT shows a low-malignant potential, but metastasizing and recurrent cases occur. In light of the probably less aggressive tumor biology and with respect to the patient's autonomy, a conservative, uterus preserving treatment appears to be justified in selected cases in which close follow-up can be guaranteed. Further case reports are needed to prove the safety of organ-preserving strategy in UTROSCT. PMID- 26369993 TI - The mitochondrial genome of Schizothorax esocinus (Cypriniformes: Cyprinidae) from Northern Pakistan. AB - The mitochondrial DNA sequence represents a mainstay of phylogenetics. It allows biologists to elucidate the evolutionary relationships among species. It also permits an examination of the relatedness of populations, hence got importance in the field of biology. The current study was designed to know the mitochondrial sequence of Schizothorax esocinus, a delicious fish belonging to family Cyprinidae. In this study, the complete mitochondrial genome of S. esocinus from Northern Pakistan was determined. The mitogenome of S. esocinus was found to be 16 591 bp in length and consisted of 13 protein coding genes, 22 tRNA genes, two rRNA genes, and one control region. All genes were encoded on heavy strain except ND6 and few tRNA genes. The overall base composition was T 25.5%, C 27.0%, A 29.8% and G 17.7%, A + T content 55.3% and G + C content 47.7%. The length of control region (CR) was 938 bp and contained putative termination-associated sequence (TAS) and several conserved sequence blocks (CSB) and control region also contained a microsatellite region (TA). This is the very first study reported from a reservoir of large cold water bodies in Pakistan which have a great potential for conservation of cold water fish species. This mitogenome sequence would be useful to know the phylogenetic status of the fish. PMID- 26369992 TI - Preliminary development of an ultrabrief two-item bedside test for delirium. AB - BACKGROUND: Delirium is common, morbid, and costly, yet is greatly under recognized among hospitalized older adults. OBJECTIVE: To identify the best single and pair of mental status test items that predict the presence of delirium. DESIGN, SETTING: Diagnostic test evaluation study that enrolled medicine inpatients aged 75 years or older at an academic medical center. METHODS: Patients underwent a clinical reference standard assessment involving a patient interview, medical record review, and interviews with family members and nurses to determine the presence or absence of Diagnostic and Statistical Manual of Mental Disorders, 4th Edition defined delirium. Participants also underwent the three-dimensional Confusion Assessment Method (3D-CAM), a brief, validated assessment for delirium. Individual items and pairs of items from the 3D-CAM were evaluated to determine sensitivity and specificity relative to the reference standard delirium diagnosis. RESULTS: Of the 201 participants (mean age 84 years, 62% female), 42 (21%) had delirium based on the clinical reference standard. The single item with the best test characteristics was "months of the year backwards" with a sensitivity of 83% (95% confidence interval [CI]: 69%-93%) and specificity of 69% (95% CI: 61%-76%). The best 2-item screen was the combination of "months of the year backwards" and "what is the day of the week?" with a sensitivity of 93% (95% CI: 81%-99%) and specificity of 64% (95% CI: 56%-70%). CONCLUSIONS: We identified a single item with >80% and pair of items with >90% sensitivity for delirium. If validated prospectively, these items will serve as an initial innovative screening step for delirium identification in hospitalized older adults. PMID- 26369994 TI - Geographical Text Analysis: A new approach to understanding nineteenth-century mortality. AB - This paper uses a combination of Geographic Information Systems (GIS) and corpus linguistic analysis to extract and analyse disease related keywords from the Registrar-General's Decennial Supplements. Combined with known mortality figures, this provides, for the first time, a spatial picture of the relationship between the Registrar-General's discussion of disease and deaths in England and Wales in the nineteenth and early twentieth centuries. Techniques such as collocation, density analysis, the Hierarchical Regional Settlement matrix and regression analysis are employed to extract and analyse the data resulting in new insight into the relationship between the Registrar-General's published texts and the changing mortality patterns during this time. PMID- 26369995 TI - Closing the door on illicit tobacco trade, opens the way to better tobacco control. PMID- 26369997 TI - Spatial accessibility of the population to urban health centres in Kermanshah, Islamic Republic of Iran: a geographic information systems analysis. AB - Geographic information systems (GIS) analysis has not been widely used in underdeveloped countries to ensure that vulnerable populations have accessibility to primary health-care services. This study applied GIS methods to analyse the spatial accessibility to urban primary-care centres of the population in Kermanshah city, Islamic Republic of Iran, by age and sex groups. In a descriptive-analytical study over 3 time periods, network analysis, mean centre and standard distance methods were applied using ArcGIS 9.3. The analysis was based on a standard radius of 750 m distance from health centres, walking speed of 1 m/s and desired access time to health centres of 12.5 mins. The proportion of the population with inadequate geographical access to health centres rose from 47.3% in 1997 to 58.4% in 2012. The mean centre and standard distance mapping showed that the spatial distribution of health centres in Kermanshah needed to be adjusted to changes in population distribution. PMID- 26369996 TI - Association between payer mix and costs, revenues and profitability: a cross sectional study of Lebanese hospitals. AB - This study aimed to examine the association between the payer mix and the financial performance of public and private hospitals in Lebanon. The sample comprised 24 hospitals, representing the variety of hospital characteristics in Lebanon. The distribution of the payer mix revealed that the main sources of revenue were public sources (61.1%), out-of-pocket (18.4%) and private insurance (18.2%). Increases in the percentage of revenue from public sources were associated with lower total costs and revenues, but not profit margins. An inverse association was noted between increased revenue from private insurance and profitability, attributed to increased costs. Increased percentage of out of- pocket payments was associated with lower costs and higher profitability. The study provides evidence that payer mix is associated with hospital costs, revenues and profitability. This should initiate/inform discussions between public and private payers and hospitals about the level of payment and its association with hospital sector financial viability. PMID- 26369998 TI - Measles vaccination coverage and seroprevalence of anti-measles antibody in south east Islamic Republic of Iran. AB - Discrepancies often exist between recorded immunization coverage and the real immunity level in a community. To estimate the vaccination coverage against measles in south-east Islamic Republic of Iran, a crosssectional study was conducted in 3 districts during summer 2011. Using probability proportional to size cluster sampling, 1368 children aged 30-54 months were selected. Serum samples of 663 who had received 2 injections of mumpsmeasles- rubella (MMR) vaccine were checked for anti-measles IgG. Vaccination coverage for the second dose of MMR vaccine was 93.7%. The prevalence of anti-measles IgG in those who had received at least 2 MMR vaccine doses was 94.6%. There was a statistically significant association between the serological results and variables that reflected poor accessibility to health services. Combining serological results with coverage data, the proportion of the community protected against measles was estimated as 88.6%, which was below the limits defined for the measles elimination goals. PMID- 26369999 TI - Knowledge, attitudes and practices of sweet food and beverage consumption and its association with dental caries among schoolchildren in Jazan, Saudi Arabia. AB - The prevalence of dental decay is expected to rise in many developing countries due to the growing consumption of sugars. This study aimed to assess knowledge, attitudes and practices of sweet food and beverage consumption among schoolchildren in Jazan, Saudi Arabia and to determine the relationship with dental caries. In a cross-sectional, descriptive study 853 children aged 6-15 years (520 boys and 333 girls) were assessed by questionnaire and clinical examinations. Caries prevalence (>= 1 dft/DMFT) was high (91.3%). While knowledge was generally good, 83.5% boys and 85.8% girls had poor attitudes to sweet foods and > 90% frequently consumed sweet foods/beverages. Multiple regression analysis showed that children whose mothers were less educated (OR 2.46; 95% CI: 1.15 5.28) and children with poor dietary attitudes and practices (OR 4.05; 95% CI: 2.33-7.03 and OR 7.80; 95% CI: 4.50-13.52 respectively) were more likely to have dental caries. Well-directed health promotion programmes are needed in Jazan. PMID- 26370000 TI - Prevalence and risk factors of diabetes mellitus in a central district in Islamic Republic of Iran: a population-based study on adults aged 40-80 years. AB - Previous studies on type 2 diabetes mellitus in the Islamic Republic of Iran were mainly performed in provinces with large populations. This study determined the prevalence and risk factors of diabetes mellitus in an adult population (40-80 years old) from Yazd district. Multistage, systematic cluster random sampling was used in a crosssectional, population-based survey. Demographic, clinical and anthropometric data were collected, with diabetes defined as fasting blood sugar >= 7 mmol/L or a positive medical history of diabetes. The age- and sex standardized prevalence of diabetes in 2090 individuals participants was 24.5% (95% CI: 22.2-26.8%), including 10.5% new cases. For each year of ageing, the prevalence of diabetes increased significantly by 4% and this trend was more pronounced in females than males. Low education and hypertension were significantly associated with diabetes prevalence. The prevalence of diabetes mellitus in Yazd is greater than the average levels nationwide and those of nearby countries. PMID- 26370001 TI - Obesity-linked diabetes in the Arab world: a review. AB - The Arab world is experiencing an epidemic of obesity and type 2 diabetes mellitus. This review summarizes the major pathological factors linking obesity to diabetes, focussing on current epidemiological data related to obese diabetic patients in the Arab world, the etiology of the disease and the genetic determinants of diabetes and obesity. There are alarming data related to the rising prevalence of obesity and type 2 diabetes mellitus in children of Arab ethnicity. Replication studies identify several genetic variants in Arabs with obesitylinked diabetes. For example, variants of the ADIPOQ gene (the rs266729 single-nucleotide polymorphism) are associated with obesity and diabetes in various Arab countries. Gaps exist in our information about diabetes and obesity in Arab populations in relation to ethnic-specific cut-off points for diagnosis and treatment of diabetes. Further genome-wide association studies in obese and diabetic Arab populations could add to our understanding of the pathophysiology, prevention and reversal of this disease. PMID- 26370002 TI - Altababa medical volunteer group mission to Almanagil hospital, Sudan: new ideas for long-term partnership, success factors and guidelines for other groups. AB - Sudanese medical volunteers have a long history of working in districts with poor health-care infrastructure. Altababa medical volunteer group (AMVG) was established by Sudanese physicians working in Saudi Arabia who desired to contribute to improving clinical services and training in their country of origin. This paper documents steps in the planning and evaluation of AMVG's first mission to Almanagil hospital in Sudan in 2013. Over a 3-day period the visiting team of 4 physicians performed 25 laparoscopic surgical and obstetric/ gynaecological procedures and 36 echocardiogram tests-all with hands-on training presented 11 lectures and consulted with 137 patients. A total of 247 trainees and patients completed a 22-item evaluation survey. The first mission was highly rated by both trainees (health-care providers) and patients. The results provided a road map for volunteers to accomplish cost-effective goals in small hospitals with modest facilities. PMID- 26370003 TI - Frequency, types and determinants of degenerative complications of type 2 diabetes in Morocco: "EpiDiaM" cohort inclusion data. AB - Degenerative complications as a result of diabetes impose a heavy disease burden and increase mortality. This study presents epidemiological and clinical profiles of diabetic patients in the EpiDiaM cohort study, which include 1196 diabetic cases recruited from the basic health care network in the city of Fez. The mean age of the participants was 57.5 (SD 10.4) years with 47.1% aged between 50 and 60 years. The majority (77.7%) were women. The mean duration of diabetes was 8 (SD 6.6) years. Hypertension was found in 49.3% of the cohort, 77.9% were overweight or obese and 63.8% had one or more complications. Among those with complications, retinopathy was the most common (69.4%), followed by heart conditions (50.8%), neuropathy (45.6%) and renal disease (4.8 %). The high prevalence of complications emphasizes the need to address the avoidable risk factors and prevent complications. PMID- 26370004 TI - WHO events addressing public health priorities. PMID- 26370005 TI - Regulatory T-cell development and function are impaired in mice lacking membrane expression of full length intercellular adhesion molecule-1. AB - To further investigate the contribution of intercellular adhesion molecule-1 (ICAM-1) to adaptive immune responses, we analysed T-cell development and function in mice lacking full-length ICAM-1 (ICAM-1(tm1Jcgr) ). Compared with wild-type (ICAM-1(WT) ) mice, ICAM-1(tm1Jcgr) mice have impaired thymocyte development. Proportions and numbers of double negative, double positive, mature CD4(+) and CD8(+) thymocytes, as well as of regulatory T (Treg) cells were also significantly decreased. In the periphery, ICAM-1(tm1Jcgr) mice had significantly decreased proportions and numbers of naive and activated/memory CD4(+) and CD8(+) T cells, as well as of Treg cells, in lymph nodes but not in the spleen. In vitro activation of CD4(+) and CD8(+) T cells from ICAM-1(tm1Jcgr) mice with anti-CD3 antibodies and antigen-presenting cells (APCs) resulted in a significantly weaker proliferation, whereas proliferation induced with anti-CD3 and anti-CD28 antibody coated beads was normal. In vivo immunization of ICAM-1(tm1Jcgr) mice resulted in normal generation of specific effector and memory immune responses that protect against a viral challenge. However, contrary to ICAM-1(WT) mice, immunization induced specific effectors could not eradicate immunogen-expressing tumours. Treg cells from ICAM-1(tm1Jcgr) mice have abnormal activation and proliferation induced by anti-CD3 antibody and APCs, and have markedly decreased suppressive activity in vitro. In contrast to ICAM-1(WT) mice, they were unable to control experimentally induced colitis in vivo. Hence, our results further highlight the pleiotropic role of ICAM-1 in T-cell-dependent immune responses, with a major role in Treg cell development and suppressive function. PMID- 26370008 TI - Low Serum Levels of Interleukin 35 in Patients with Rheumatoid Arthritis. AB - Interleukin 35 (IL-35) is a newly discovered anti-inflammatory cytokine. Recent studies have indicated that it plays a crucial role in the pathogenesis of autoimmune diseases. In humans, IL-35 is predominantly secreted from regulatory T cells. This study aimed to measure serum IL-35 levels in patients with rheumatoid arthritis (RA) and in control individuals, and analyze its association with disease indicators of RA. One hundred patients with RA were recruited, and 50 volunteers were enrolled as healthy controls. Serum IL-35 levels were measured using an enzyme-linked immunosorbent assay kit. RA patients showed significantly lower serum levels of IL-35 compared with healthy controls (p < 0.001). RA patients suffering from erosive arthritis (n = 31) had lower IL-35 levels than those with non-erosive arthritis (n = 69, p = 0.022). In addition, serum IL-35 level was significantly lower in 22 patients with elevated percentage (> 75%) of neutrophils (p < 0.001). Correlation analysis indicated a significantly negative association between IL-35 and age, rheumatoid factor (RF), or percentage of neutrophils. In contrast, the serum IL-35 levels were not significantly different between patients with anti-cyclic citrullinated peptide (CCP) antibodies (n = 78) and those without anti-CCP antibodies (n = 22). However, among patients without anti-CCP antibodies, the serum IL-35 levels were lower in patients with erosive arthritis (n = 8) than those patients without erosion (n = 14) (p < 0.001), although no significant difference was detected in patients with anti-CCP antibodies. In conclusion, IL-35 plays a protective role in the pathogenesis of RA. PMID- 26370006 TI - A patient showing features of both SBBYSS and GPS supports the concept of a KAT6B related disease spectrum, with mutations in mid-exon 18 possibly leading to combined phenotypes. AB - Genitopatellar syndrome (GPS) and Say-Barber-Biesecker-Young-Simpson syndrome (SBBYSS) are two distinct clinically overlapping syndromes caused by de novo heterozygous truncating mutations in the KAT6B gene encoding lysine acetyltransferase 6B, a part of the histone H3 acetyltransferase complex. We describe an 8-year-old girl with a KAT6B mutation and a combined GPS/SBBYSS phenotype. The comparison of this patient with 61 previously published cases with KAT6B mutations and GPS, SBBYSS or combined GPS/SBBYSS phenotypes allowed us to separate the KAT6B mutations into four groups according to their position in the gene (reflecting nonsense mediated RNA decay and protein domains) and their clinical outcome. We suggest that mutations in mid-exon 18 corresponding to the C terminal end of the acidic (Asp/Glu-rich) domain of KAT6B may have more variable expressivity leading to GPS, SBBYSS or combined phenotypes, in contrast to defects in other regions of the gene which contribute more specifically to either GPS or SBBYSS. Notwithstanding the clinical overlap, our cluster analysis of phenotypes of all known patients with KAT6B mutations supports the existence of two clinical entities, GPS and SBBYSS, as poles within the KAT6B-related disease spectrum. The awareness of these phenomena is important for qualified genetic counselling of patients with KAT6B mutations. PMID- 26370011 TI - Celebrating the ACP Centennial: From the Annals Archive-Ankylosing Spondylitis. PMID- 26370007 TI - Mechanisms regulating spill-over of synaptic glutamate to extrasynaptic NMDA receptors in mouse substantia nigra dopaminergic neurons. AB - N-Methyl-D-aspartate glutamate receptors (NMDARs) contribute to neural development, plasticity and survival, but they are also linked with neurodegeneration. NMDARs at synapses are activated by coincident glutamate release and depolarization. NMDARs distal to synapses can sometimes be recruited by 'spill-over' of glutamate during high-frequency synaptic stimulation or when glutamate uptake is compromised, and this influences the shape of NMDAR-mediated postsynaptic responses. In substantia nigra dopamine neurons, activation of NMDARs beyond the synapse during different frequencies of presynaptic stimulation has not been explored, even though excitatory afferents from the subthalamic nucleus show a range of firing frequencies, and these frequencies change in human and experimental Parkinson's disease. This study reports that high-frequency stimulation (80 Hz/200 ms) evoked NMDAR-excitatory postsynaptic currents (EPSCs) that were larger and longer lasting than those evoked by single stimuli at low frequency (0.1 Hz). MK-801, which irreversibly blocked NMDAR-EPSCs activated during 0.1-Hz stimulation, left a proportion of NMDAR-EPSCs that could be activated by 80-Hz stimulation and that may represent activity of NMDARs distal to synapses. TBOA, which blocks glutamate transporters, significantly increased NMDAR-EPSCs in response to 80-Hz stimulation, particularly when metabotropic glutamate receptors (mGluRs) were also blocked, indicating that recruitment of NMDARs distal to synapses is regulated by glutamate transporters and mGluRs. These regulatory mechanisms may be essential in the substantia nigra for restricting glutamate diffusion from synaptic sites and keeping NMDAR-EPSCs in dopamine neurons relatively small and fast. Failure of glutamate transporters may contribute to the declining health of dopamine neurons during pathological conditions. PMID- 26370012 TI - On Losing Your Humanity. PMID- 26370013 TI - Statins for Primary Prevention in Adults Aged 75 Years or Older. PMID- 26370014 TI - Statins for Primary Prevention in Adults Aged 75 Years or Older. PMID- 26370015 TI - Statins for Primary Prevention in Adults Aged 75 Years or Older. PMID- 26370016 TI - Metformin Prescription for Insured Adults With Prediabetes From 2010 to 2012. PMID- 26370017 TI - Metformin Prescription for Insured Adults With Prediabetes From 2010 to 2012. PMID- 26370018 TI - Low-Molecular-Weight Heparin for Women With Unexplained Recurrent Pregnancy Loss. PMID- 26370019 TI - Low-Molecular-Weight Heparin for Women With Unexplained Recurrent Pregnancy Loss. PMID- 26370020 TI - Low-Molecular-Weight Heparin for Women With Unexplained Recurrent Pregnancy Loss. PMID- 26370021 TI - Firearms Among Cognitively Impaired Persons: A Cross-sectional Study. PMID- 26370022 TI - Decrease in Surgery for Clostridium difficile Infection After Starting a Program to Transplant Fecal Microbiota. PMID- 26370024 TI - Web Exclusives. The Consult Guys--Proceed to Surgery: Are You Kidding Me? PMID- 26370025 TI - In unexplained recurrent pregnancy loss, daily LMWH did not improve ongoing pregnancy or live birth rates. PMID- 26370026 TI - In postmenopausal women with breast cancer treated with aromatase inhibitors, denosumab reduced fractures. PMID- 26370027 TI - Obstructive sleep apnea in US veterans was associated with increased mortality and morbidity. PMID- 26370028 TI - Neither dabigatran nor rivaroxaban were linked to increased GI bleeding compared with warfarin. PMID- 26370029 TI - Review: Type 2 diabetes screening does not reduce mortality but treating dysglycemia delays onset of diabetes. PMID- 26370030 TI - Review: Influenza vaccination and inhaled therapies prevent acute exacerbations in COPD. PMID- 26370031 TI - Review: Cannabinoids may improve symptoms for some indications but increase adverse events. PMID- 26370032 TI - In non-ICU suspected CAP, beta-lactam was noninferior to beta-lactam-macrolide or fluoroquinolone for 90-d mortality. PMID- 26370033 TI - Review: After coronary DES placement, longer vs shorter DAPT increases major bleeding and death and reduces MI. PMID- 26370034 TI - Adding ezetimibe to simvastatin improved cardiovascular outcomes in stable acute coronary syndrome. PMID- 26370035 TI - Review: Immediate vs deferred antiepileptics reduce recurrence at 1 to 2 y after an unprovoked first seizure. PMID- 26370036 TI - Disease activity-guided TNF inhibitor dose reduction was noninferior to continuing TNF inhibitors for RA flares. PMID- 26370037 TI - Reconstruction of the evolutionary history of Haemosporida (Apicomplexa) based on the cyt b gene with characterization of Haemocystidium in geckos (Squamata: Gekkota) from Oman. PMID- 26370038 TI - Shp2 signaling suppresses senescence in PyMT-induced mammary gland cancer in mice. PMID- 26370039 TI - Perceived Effects of Occupational Hazards on Farmers' Productivity in Kwara State, Nigeria. AB - This study investigated the perceived effects of occupational hazards on farmers' productivity in Kwara State, Nigeria. A total of 160 respondents were selected using a multi-stage random sampling technique. Descriptive statistical techniques such as frequency count, percentages as well as Pearson Product Moment correlation analysis for empirical analysis were used. The results show common agricultural production to include maize, yam and cassava. The results also revealed prevalent occupational hazards that include cut/injury from farm tools, malaria due to mosquito bite, and general body pain. The findings further revealed that injury from farm tools and general body pain had high effects on agricultural productivity. The Pearson Product Moment Correlation analysis showed no significant relationship (P<=0.05) between selected socio-economic characteristics with the perceived effects of occupational hazards on productivity. Based on the findings, the study concludes that occupational (farming) hazards, most especially general body pain, had negative effects on agricultural productivity. The study recommends that government and relevant agencies should encourage farmers by providing for them protective equipment at subsidized cost through extension agents who will train farmers on their use. Also, public health agents should educate farmers on personal health care practices in order to ensure good health status of farmers. PMID- 26370040 TI - A Case of Rapid Exacerbation of Pulmonary Mycobacterium Avium Complex Infection Mimicking Pulmonary Aspergillosis. AB - We herein report a case of pulmonary Mycobacterium avium complex (MAC) infection with pulmonary multiple nodules and the "halo sign" on chest computed tomography (CT) in which the patient showed rapid exacerbation seven years after undergoing bone marrow transplantation (BMT). A 68-year-old Japanese female visited our hospital due to a productive cough and dyspnea. She had undergone allogeneic BMT for acute myelocytic leukemia and received both prednisolone (2 mg/day) and cyclosporine (30 mg/day). Chest CT demonstrated no abnormal findings on admission; however, multiple pulmonary nodules and the "halo sign" were detected three weeks later. Although a fungal infection was initially suspected, a bronchoscopic examination revealed pulmonary MAC infection. In the present case, pulmonary MAC infection exhibited rapid progression with unique CT findings. Physicians should consider MAC infection in the differential diagnosis in patients who receive BMT and/or immunosuppressive agents, even if the clinical and radiological findings are atypical of the disease. PMID- 26370041 TI - Negative Pressure Wound Therapy with Surgical Gloves to Repair Soft Tissue Defects in Hands. AB - The efficacy of negative pressure wound therapy (NPWT) in the treatment of skin defect wounds has been established, but it is difficult to apply to hand surgery because of the easy occurrence of air leaks. We report two cases of performing NPWT with surgical gloves. Case1: A 37-year-old male was injured on his right dorsal hand from a punch. He presented to our hospital three days after the injury because of swelling and pain. The wound was infected and contused, so wound lavage and debridement (W&D) were performed under local anesthesia. The infected condition didn't improve after antimicrobial infusion, so W&D were performed again 8 days after the first visit. Then W&D were performed every day, and the infection subsided 15 days after the first visit. NPWT was initiated for the purpose of managing exudate and the wound condition, and healthy granulation tissue formed gradually. Finally, transpositional flap and full-thickness skin graft were performed on day 29. Case2: A 43-year-old male accidentally sustained a high pressure injection of oil into his dorsal hand. He presented to our hospital the next day, and W&D were performed. W&D were performed again two days after the first visit, and artificial dermis was applied over a part of the wound that was impossible to close. A decision was made to apply NPWT and a surgical glove for the purpose of reducing swelling and managing wound exudate. The swelling decreased and granulation tissue formed gradually, then nine days after the first visit a sural nerve graft was applied to bridge the defective area, and a full thickness skin graft was applied. We achieved good wound closure and hand function recovery after using NPWT and a surgical glove. PMID- 26370042 TI - [Intrapericardial Vessel Management for Lung Cancer Surgery]. AB - Intrapericardial vessel management is one of the necessary techniques for respiratory surgeons. We collected cases that had undergone intrapericardial vessel management for lung cancer, and herein discuss the practical performance and safety of this treatment method. We identified 23 (5.6%) of 413 patients who had undergone lung cancer surgery during the 30-month period from January 2011 to June 2013 at our institution. Twenty cases had large sized tumors near the hilum. Three cases demonstrated severe adhesion in the intrathoracic region due to a previous operation. The lung cancer staging was stage IA in 1 case, stage IB in 4 cases, stage IIB in 5 cases, stage IIIA in 11 cases, stage IIIB in 1 case, and stage IV in 1 case. We performed lobectomy in 11 cases, bilobectomy in 6 cases, and pneumonectomy in 6 cases. The average operation time was 366 minutes (137 965). Post operative complications were observed in five cases, including two cases of air-leakage and three cases of arrhythmia. All cases were able to walk on foot at discharge. It is important to clearly understand intrapericardial anatomy in order to carry out successful intrapericadial vessel management. PMID- 26370043 TI - [Mitral Valve Repair for Patients with Mitral Valve Prolapse]. AB - Prosthetic valve replacement has mainly been performed on patients with mitral regurgitation. In such cases, prosthetic valve related complications, such as thromboembolism, bleeding, prosthetic valve infection, and structural valve deterioration, are unavoidable. With valve plasty, however, not only can such complications be avoided, but patients can also have as good a quality of life as healthy people without medications. Although mitral valve plasty requires complicated techniques like chordal reconstruction and has problems of residue, recurrence, and progression of regurgitation, patients with mitral valve prolapse are considered to be good candidates for this procedure. Mitral annuloplasty with a prosthetic ring is the essential and basic procedure of this operation, usually adding to the other techniques. Resection and suture methods of quadrangular resection, triangular resection and the sliding method, by which systolic anterior movement can be avoided, are indicated for patients with posterior leaflets prolapse. The resection and suture method, chordal shortening, and chordal transposition were previously done on patients with anterior leaflets prolapse, but recently chordal reconstruction using ePTFE (expanded polytetrafluoroethylene) is performed. Superior long-term results of mitral valve plasty for patients with mitral valve prolapse compared to prosthetic valve replacement have been reported. The 10-year reoperation rate of mitral valve plasty is only 7-10% as much as valve replacement. PMID- 26370044 TI - [A Literature Review of Health Effects on Workers in Disasters]. AB - Various types of disasters, such as natural disasters, industrial accidents and crimes, often occur in the workplace and many workers are involved in them. They are not only directly injured but also exposed to health hazards, such as terrible experiences and chemical materials. Occupational health specialists are expected to act to minimize the adverse health effects from them speedily and appropriately. It is assumed that learning from past cases is effective for such occupational health activities. Accordingly, we conducted a literature review about the health effects on workers in disasters. Relevant literature was searched in PubMed. Twenty four studies were extracted by our criteria. In this review, subjects were limited to general workers by excluding professional workers, such as emergency services and firefighters. The health effects were examined as follows: mental health (13 articles), respiratory (5), cardiovascular (2), musculoskeletal (1), skin (1), nervous (1), and general (1). It was obvious that few studies on general workers were published when considering large number of disasters in the past. Factors that affect health outcomes were categorized into 1 those related to devastation of environment of work and life due to disaster, and 2 those related to health hazards due to disasters. Knowledge from the review will support the activities of occupational health specialists during disasters, but additional studies are needed. PMID- 26370045 TI - [An Evaluation of Visual Function in Working Age Patients with Glaucoma]. AB - Visual function affects working ability in occupational health. We investigated the frequencies and grades of low vision in working age people who have glaucoma, and studied patients who were receiving low vision care, for example eye movement training. Among 3,905 patients aged 15 to 64 years old who visited Murakami eye clinic from October 2013 to September 2014, there were 363 patients suspected of having glaucoma and 138 patients diagnosed with glaucoma and receiving treatment. We measured their visual acuity and visual field to calculate their functional vision score (FVS). We studied the amount of reduction in visual ability and the number of patients undergoing low vision care by age groups. The vision test and visual field test showed that 18 patients had reduced visual ability, according to the FVS. Their FVS classification was from class 1 (mild vision loss) to class 3a (severe vision loss). The FVS matches the statistics of the WHO and can predict the reading and walking ability in each class. Reduced visual ability was recognized in about 14% of the glaucoma patients older than 45 years of age. 78% of the patients were classified in class 1. In FVS, class 2 (moderate vision loss) or greater is defined as low vision, and class 1 is a condition with no visual reserve. Although such patients have no problems in daily life and office work, they are challenged by on-site work and the on-site environment, and occupational health staff intervention becomes necessary. PMID- 26370046 TI - [Evaluation of Educational Effect of Problem-Posing System in Nursing Processing Study]. AB - The nursing processing study is generally difficult, because it is important for nursing college students to understand knowledge and utilize it. We have developed an integrated system to understand, utilize, and share knowledge. We added a problem-posing function to this system, and expected that students would deeply understand the nursing processing study through the new system. This system consisted of four steps: create a problem, create an answer input section, create a hint, and verification. Nursing students created problems related to nursing processing by this system. When we gave a lecture on the nursing processing for second year students of A university, we tried to use the creating problem function of this system. We evaluated the effect by the number of problems and the contents of the created problem, that is, whether the contents consisted of a lecture stage or not. We also evaluated the correlation between those and regular examination and report scores. We derived the following: 1. weak correlation between the number of created problems and report score (r=0.27), 2. significant differences between regular examination and report scores of students who created problems corresponding to the learning stage, and those of students who created problems not corresponding to it (P<0.05). From these results, problem-posing is suggested to be effective to fix and utilize knowledge in the lecture of nursing processing theory. PMID- 26370047 TI - [The Clinical Features of Cerebrospinal Fluid Leaks--Based on Our Experiences]. AB - Cerebrospinal fluid (CSF) leak, which usually occurs idiopathically or traumatically as a rare situation, is a rare disease that causes orthostatic headache or idiopathic chronic subdural hematoma (CSDH). We report our therapeutic experience of consecutive 20 cases for this disease, and review the current status and problems. Consecutive 20 patients (11 women; age 44.7+/-12.1 years) between April, 2006 and March, 2014, who were diagnosed by MRI and/or CT myelography (CTM), were evaluated retrospectively about clinical features. The main symptoms were as follows: orthostatic headache only; 10 cases, orthostatic headache with CSDH; 6, and none-orthostatic headache accompanied with CSDH; 4. As a treatment, direct surgeries were performed in 2 cases. Epidural blood patch (EBP) was applied in 14 cases (direct surgery was performed finally in the early one case), and widespread EBP with a single lumbar entry point utilizing an intravenous catheter was performed especially in the latest 9 cases. Another 5 cases were treated simply with the administration of a drip infusion regardless of the drainage for CSDH. Of 10 cases suffering from headache only, the headache disappeared completely or it was relieved in 9 cases. Of 10 cases accompanied with CSDH, recurrence of hematoma was prevented in all cases with a drip infusion after the drainage in one case and EBP after the drainage in another 9 cases. It was certified that we could diagnose CSF leak correctly with MRI and/or CTM and control this disorder almost completely with widespread EBP utilizing an intravenous catheter. PMID- 26370049 TI - Nitrous oxide emissions during biological soil disinfestation with different organic matter and plastic mulch films in laboratory-scale tests. AB - Nitrous oxide (N2O), which is a greenhouse gas, may be more emitted as an intermediate product of denitrification during biological soil disinfestation. The biological soil disinfestation is a method to suppress soil-borne pathogens under reductive soil conditions produced by the application of organic matter and water irrigation with plastic film. The objective of the study was to determine the effects of different organic matter and mulch films on N2O emissions during biological soil disinfestation. Grey lowland soil amended with cattle compost plus rice bran (0.2%), rice husk (0.2%) or dent corn (0.1%, 0.2% and 0.4%) was incubated at 100% water-holding capacity with or without plastic films made of polyvinyl chloride (PVC) and triple-layer polyolefin (3PO) for 72 h at 50 degrees C. Permeation of the two films was also measured at 25 degrees C and 50 degrees C. Results showed that incorporation of organic matter increased N2O emissions compared with no organic matter addition at 50 degrees C. Incorporation of rice bran and dent corn with easily decomposable C and low C:N ratios increased N2O emissions for the first 12 h, but thereafter, available C supply from these amendments suppressed N2O emissions. Permeability of mulch films increased at a higher temperature and was larger for PVC than for 3PO. Our study indicated that rice husk should not be used for soil disinfestation and that application rates of organic matter must be determined based on their decomposability. Moreover, mulch film covering would not suppress N2O emission in biological soil disinfestation because of high temperature. PMID- 26370052 TI - From bedlam to bioethics: Where did my psychodramatic childhood lead me? PMID- 26370050 TI - AHR promoter variant modulates its transcription and downstream effectors by allele-specific AHR-SP1 interaction functioning as a genetic marker for vitiligo. AB - Vitiligo is an acquired depigmentation disorder largely caused by defective melanocyte- or autoimmunity-induced melanocyte destruction. The aryl hydrocarbon receptor (AHR) is essential for melanocyte homeostasis and immune process, and abnormal AHR was observed in vitiligo. We previously identified the T allele of AHR -129C > T variant as a protective factor against vitiligo. However, biological characterization underlying such effects is not fully certain, further validation by mechanistic research is warranted and was conducted in the present study. We showed that -129T allele promoted AHR transcriptional activity through facilitating its interaction with SP1 transcription factor (SP1) compared with 129C allele. We subsequently found reduced peripheral AHR and SP1 transcript expressions in vitiligo and a negative correlation of AHR level with disease duration. We also investigated AHR-related cytokines and observed increased serum TNF-alpha concentration and diminished serum levels of IL-10 and TGF-beta1 in vitiligo. Further genetic analysis showed that -129T carriers possessed higher levels of AHR and IL-10 than -129C carriers. Therefore, our study indicates that the modulation of AHR transcription by a promoter variant has a profound influence on vitiligo, not only advancing our understanding on AHR function but also providing novel insight into the pathogenesis of degenerative or autoimmune diseases including vitiligo. PMID- 26370051 TI - Two-photon absorption of fluorescent protein chromophores incorporating non canonical amino acids: TD-DFT screening and classical dynamics. AB - Two-photon spectroscopy of fluorescent proteins is a powerful bio-imaging tool characterized by deep tissue penetration and little damage. However, two-photon spectroscopy has lower sensitivity than one-photon microscopy alternatives and hence a protein with a large two-photon absorption cross-section is needed. We use time-dependent density functional theory (TD-DFT) at the B3LYP/6-31+G(d,p) level of theory to screen twenty-two possible chromophores that can be formed upon replacing the amino-acid Tyr66 that forms the green fluorescent protein (GFP) chromophore with a non-canonical amino acid. A proposed chromophore with a nitro substituent was found to have a large two-photon absorption cross-section (29 GM) compared to other fluorescent protein chromophores as determined at the same level of theory. Classical molecular dynamics are then performed on a nitro modified fluorescent protein to test its stability and study the effect of the conformational flexibility of the chromophore on its two-photon absorption cross section. The theoretical results show that the large cross-section is primarily due to the difference between the permanent dipole moments of the excited and ground states of the nitro-modified chromophore. This large difference is maintained through the various conformations assumed by the chromophore in the protein cavity. The nitro-derived protein appears to be very promising as a two photon absorption probe. PMID- 26370053 TI - Election 2015: Health issues primer. PMID- 26370054 TI - Names of researchers who commit fraud may be disclosed. PMID- 26370056 TI - Arsenic exposure linked to diabetes risk in Canada. PMID- 26370055 TI - Recommendations for preventing fracture in long-term care. PMID- 26370057 TI - Electrofocusing-enhanced localized surface plasmon resonance biosensors. AB - Localized surface plasmon resonance (LSPR) biosensors typically suffer from diffusion limited mass transport and nonspecific adsorption upon detection of biomolecules in real biofluids. We employ here a peptide-modified plasmonic gold nanohole (AuNH) array for real-time detection of human troponin I (cTnI). Applying a negative electric bias on the AuNH sensor chip enables us to attract and concentrate cTnI at the sensor surface, while repelling other proteins thus decreasing interferences due to nonspecific adsorption. PMID- 26370058 TI - How Leiomodin and Tropomodulin use a common fold for different actin assembly functions. AB - How proteins sharing a common fold have evolved different functions is a fundamental question in biology. Tropomodulins (Tmods) are prototypical actin filament pointed-end-capping proteins, whereas their homologues, Leiomodins (Lmods), are powerful filament nucleators. We show that Tmods and Lmods do not compete biochemically, and display similar but distinct localization in sarcomeres. Changes along the polypeptide chains of Tmods and Lmods exquisitely adapt their functions for capping versus nucleation. Tmods have alternating tropomyosin (TM)- and actin-binding sites (TMBS1, ABS1, TMBS2 and ABS2). Lmods additionally contain a C-terminal extension featuring an actin-binding WH2 domain. Unexpectedly, the different activities of Tmods and Lmods do not arise from the Lmod-specific extension. Instead, nucleation by Lmods depends on two major adaptations-the loss of pointed-end-capping elements present in Tmods and the specialization of the highly conserved ABS2 for recruitment of two or more actin subunits. The WH2 domain plays only an auxiliary role in nucleation. PMID- 26370059 TI - Differences in XPS and solid state NMR spectral data and thermo-chemical properties of iso-structural compounds in the series KTaF6, K2TaF7 and K3TaF8 and KNbF6, K2NbF7 and K3NbF8. AB - A series of compounds KTaF6, K2TaF7 and K3TaF8 and KNbF6, K2NbF7 and K3NbF8 was investigated by means of XPS and MAS NMR spectroscopy and DSC measurements. Electron binding energies of all accessible orbitals were discussed and, for the first time, correlations between different orbital energies were examined. (19)F MAS NMR data and other NMR parameters of the investigated compounds were correlated with structural information, as well as with XPS data. Also a complete set of DSC data was presented including a number of phase transitions and their heat contents. Based on measured characteristics it was shown how differences in the electronic structure of isostructural compounds influence the spectral and thermo-chemical behaviour of the investigated pairs, i.e. KTaF6vs. KNbF6, K2TaF7vs. K2NbF7 and K3TaF8vs. K3NbF8. It was concluded that the differences in K 2s orbital energies play an important role in the different behaviour of tantalate and niobate analogues. PMID- 26370060 TI - Target dependent femtosecond laser plasma implantation dynamics in enabling silica for high density erbium doping. AB - Chemical dissimilarity of tellurium oxide with silica glass increases phase separation and crystallization tendency when mixed and melted for making a glass. We report a novel technique for incorporating an Er(3+)-doped tellurite glass composition into silica substrates through a femtosecond (fs) laser generated plasma assisted process. The engineered material consequently exhibits the spectroscopic properties of Er(3+)-ions, which are unachievable in pure silica and implies this as an ideal material for integrated photonics platforms. Formation of a well-defined metastable and homogeneous glass structure with Er(3+)-ions in a silica network, modified with tellurite has been characterized using high-resolution cross-sectional transmission electron microscopy (HRTEM). The chemical and structural analyses using HRTEM, Rutherford backscattering spectrometry (RBS) and laser excitation techniques, confirm that such fs-laser plasma implanted glasses may be engineered for significantly higher concentration of Er(3+)-ions without clustering, validated by the record high lifetime-density product 0.96 * 10(19) s.cm(-3). Characterization of planar optical layers and photoluminescence emission spectra were undertaken to determine their thickness, refractive indices and photoluminescence properties, as a function of Er(3+) concentration via different target glasses. The increased Er(3+) content in the target glass enhance the refractive index and photoluminescence intensity of the modified silica layer whilst the lifetime and thickness decrease. PMID- 26370061 TI - Prevention of contrast-induced nephropathy with single bolus erythropoietin in patients with diabetic kidney disease: A randomized controlled trial. AB - AIM: Contrast-induced-nephropathy (CIN) is associated with poor outcomes, thus prevention of CIN may be of clinical value. Erythropoietin (EPO) has been shown to elicit tissue-protective effects in experimental models and in clinical studies of acute kidney injury. We therefore evaluated its effectiveness for prevention of CIN after coronary angiography (CA) +/- percutaneous coronary intervention (PCI) in diabetic patients with chronic kidney disease. METHODS: A prospective, randomized, controlled trial was carried out in 138 diabetic patients with eGFR <60 mL/min who underwent non-urgent CA +/- PCI. Patients received normal saline and n-acetyl cysteine before CA, with or without 50,000 U of EPO administered 30 min prior to CA. CIN was defined as an increase in serum creatinine of at least 0.5 mg/dL during the first 2 days after exposure to contrast media. Primary outcome was the incidence of CIN. Secondary outcomes were the sensitivity and positive predictive value (PPV) of Cystatin C (CC) and Neutrophil-gelatinase-associated-lipocalin (NGAL) for diagnosis of CIN. RESULTS: The observed incidence of CIN was 8.7%, significantly lower than the expected for such high-risk population. The administration of EPO prior to CA did not reduce the incidence of CIN (9.7% vs. 7.6%, P = 0.65). CC and NGAL demonstrated a low sensitivity (16.6%) and low PPV (6.7 and 33.3%, respectively) for detecting CIN. CONCLUSION: The administration of EPO prior to CA did not reduce the incidence of CIN. Additional prospective research with a larger sample size and in other patient categories is essential to further define the potential protective effect of EPO on prevention of CIN. PMID- 26370062 TI - European EADV network on assessment of severity and burden of Pruritus (PruNet): first meeting on outcome tools. AB - BACKGROUND: Chronic pruritus is a frequently occurring symptom of various dermatoses that causes a high burden and impaired quality of life. An effective anti pruritic therapy is important for the patient, but its effectiveness is difficult to evaluate. Diverse methods and interpretations of pruritic metrics are utilized in clinical trials and the daily clinical practice in different countries, resulting in difficulties comparing collected data. METHODS: We founded a European Network on Assessment of Severity and Burden of Pruritus (PruNet) that is supported by the EADV. PruNet consists of 28 experts from 15 EU countries (21 dermatologists, 5 medical informaticists, 2 psychologists) and aims to unify the assessment of itch in routine dermatological care. Following a preliminary survey, a consensus conference was held in order to agree upon the prioritization of patient-reported outcome tools. RESULTS: Through utilizing the Delphi method, it was agreed that tools for measuring itch intensity (ex. the visual analogue scale) and quality of life (ex. ItchyQoL) are of primary importance and should urgently be foremost validated. CONCLUSION: The validation and harmonization of standards are needed for the improvement of quality care for patients suffering from pruritic dermatoses. This summer, the first validation studies in several EADV member countries already began. PMID- 26370063 TI - Management of cerebrospinal fluid rhinorrhea: an evidence-based review with recommendations. AB - BACKGROUND: Management strategies employed for cases of cerebrospinal fluid (CSF) rhinorrhea vary widely because of limited evidence-based guidance. METHODS: A systematic review of the literature was performed using PubMed, EMBASE, and Cochrane databases from January 1990 through September 2014 to examine 5 endoscopic repair techniques and 8 perioperative management strategies for CSF rhinorrhea. Benefit-harm assessments, value judgments, and recommendations were made based on the available evidence. Study exclusion criteria were language other than English, pre-1990 studies, case reports, and nonrhinologic leak. All authors agreed on recommendations through an iterative process. RESULTS: We reviewed 67 studies examining 13 practices pertinent to the management of CSF rhinorrhea, reaching a highest aggregate grade of evidence of B. The literature does not support the routine use of prophylactic antibiotics or lumbar drainage. Various endoscopic repair materials show similar success rates; however, larger defects may benefit from vascularized grafts. There were no relevant studies to address postoperative activity restrictions. CONCLUSION: Despite relatively low levels of evidence, recommendations for the management of CSF rhinorrhea can be made based on the current literature. Higher-level studies are needed to better determine optimal clinical management approaches. PMID- 26370064 TI - Evaluation of the efficacy of animal-assisted therapy based on the reality orientation therapy protocol in Alzheimer's disease patients: a pilot study. AB - BACKGROUND: The aim of this study was to evaluate the efficacy of animal-assisted therapy (AAT) in elderly patients affected by Alzheimer's disease based on the formal reality orientation therapy (ROT) protocol. METHODS: Our study was carried out at an Alzheimer's centre for 6 months. A homogeneous sample (age, Mini-Mental State Examination (MMSE), 15-item Geriatric Depression Scale (GDS)) of 50 patients was selected at random and successively. Patients were divided into three groups: (i) 20 patients received a course of AAT (AAT group) based on the ROT protocol; (ii) 20 patients were engaged exclusively in activities based on the ROT group; and (iii) 10 patients (control group) participated in no stimulations. MMSE and GDS were administered at time 0 (T0 ) and time 1 (T1 ) to all three groups. Differences within groups between T0 and T1 for GDS and MMSE scores were analyzed by Student's t-test. Differences between group means were analyzed using an anova test with the Bonferroni-Dunn test for post-hoc comparisons. RESULTS: Both the AAT group and ROT group had improved GDS scores and showed a slight improvement in terms of mood. On the GDS, the AAT group improved from 11.5 (T0 ) to 9.5 (T1 ), and the ROT group improved from 11.6 (T0 ) to 10.5 (T1 ). At the same time, a slight improvement in cognitive function, as measured by the MMSE, was observed. In the AAT group, mean MMSE was 20.2 at T0 and 21.5 at T1 , and in the ROT group, it was 19.9 at T0 and 20.0 at T1 . In the control group, the average values of both the GDS and MMSE remained unchanged. The Bonferroni-Dunn results showed statistically significant differences between groups, particularly between the AAT group and the other two (P < 0.001). CONCLUSIONS: Pet therapy interventions based on the formal ROT protocol were effective and, compared to the ROT, provided encouraging and statistically significant results. PMID- 26370065 TI - Relationship of multiscale entropy to task difficulty and sway velocity in healthy young adults. AB - PURPOSE/BACKGROUND: Multiscale entropy (MSE) is a nonlinear measure of postural control that quantifies how complex the postural sway is by assigning a complexity index to the center of pressure (COP) oscillations. While complexity has been shown to be task dependent, the relationship between sway complexity and level of task challenge is currently unclear. This study tested whether MSE can detect short-term changes in postural control in response to increased standing balance task difficulty in healthy young adults and compared this response to that of a traditional measure of postural steadiness, root mean square of velocity (VRMS). METHODS: COP data from 20 s of quiet stance were analyzed when 30 healthy young adults stood on the following surfaces: on floor and foam with eyes open and closed and on the compliant side of a Both Sides Up (BOSU) ball with eyes open. Complexity index (CompI) was derived from MSE curves. RESULTS: Repeated measures analysis of variance across standing conditions showed a statistically significant effect of condition (p < 0.001) in both the anterior posterior and medio-lateral directions for both CompI and VRMS. In the medio lateral direction there was a gradual increase in CompI and VRMS with increased standing challenge. In the anterior-posterior direction, VRMS showed a gradual increase whereas CompI showed significant differences between the BOSU and all other conditions. CompI was moderately and significantly correlated with VRMS. CONCLUSIONS: Both nonlinear and traditional measures of postural control were sensitive to the task and increased with increasing difficulty of standing balance tasks in healthy young adults. PMID- 26370066 TI - Entecavir treatment may be associated with decreased libido in male patients with chronic hepatitis B: report of two cases. AB - Various types of drugs are being used to treat patients with chronic hepatitis B infection. However, these treatment modalities are not without side effects, which may result in decreased patient adherence. Entecavir is an oral reverse transcriptase inhibitor, which is widely used in patients with hepatitis B. Although headache, fatigue and nausea are well-documented side effects of entecavir, its sexual side effects have not been reported yet. We here report on two male patients with chronic hepatitis B infection who reported decreased libido under entecavir treatment. PMID- 26370067 TI - Development of a synthetic receptor protein for sensing inflammatory mediators interferon-gamma and tumor necrosis factor-alpha. AB - Intestinal inflammation has been implicated in a number of diseases, including diabetes, Crohn's disease, and irritable bowel syndrome. Important components of inflammation are interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha), which are elevated both on the luminal and submucosal sides of the intestinal epithelial barrier in several diseases. Here, we developed a novel Escherichia coli based detection system for IFN-gamma and TNF-alpha comprised of a chimeric protein and a simple signal transduction construct, which could be deployed on the luminal side of the intestine. OmpA of E. coli was engineered to detect IFN-gamma or TNF-alpha through the replacement of extracellular loops with peptide fragments from OprF of P. aeruginosa. OmpA/OprF chimeras were developed, capable of binding IFN-gamma or TNF-alpha. The specific peptide fragments that bind IFN-gamma were identified. IFN-gamma or TNF-alpha binding the OmpA/OprF chimera induced the pspA promoter, driving beta-galactosidase production. The OmpA/OprF chimera had a detection limit of 300 pM for IFN-gamma and 150 pM for TNF-alpha. This work will further the development of bacteria based therapeutics for the treatment of inflammatory diseases of the gut. PMID- 26370068 TI - Herpes simplex virus 2 hepatitis in a lung transplant recipient: a diagnostic challenge. AB - Herpes simplex virus (HSV) hepatitis is a rare and serious complication in immunocompromised patients. We report the case of an HSV hepatitis occurring 4 years after lung transplantation in a cystic fibrosis patient. The presentation was nonspecific, mimicking acute cholecystitis; orogenital signs were absent. The diagnosis was made based on viral cultures performed during cholecystectomy and confirmed by blood quantitative polymerase chain reaction. Although the diagnosis and treatment were delayed, the patient fully recovered with acyclovir, reduced immunosuppression, and intravenous immunoglobulins. The diagnostic difficulties, prognostic factors, and treatments of this infection are discussed. PMID- 26370069 TI - Incontinence in children, adolescents and adults with Williams syndrome. AB - AIMS: Williams Syndrome (WS) is a microdeletion syndrome (chromosome 7q11.23) characterized by typical facial features, cardiovascular disease, behavioural symptoms, and mild intellectual disability (ID). The aim of this study was to assess the rates of incontinence and psychological problems in persons with WS. METHODS: 231 individuals with WS were recruited through the German parent support group (52.0% male, mean age 19.4 years). Faecal incontinence (FI) was diagnosed from the age of 4 years and nocturnal enuresis (NE) and daytime urinary incontinence (DUI) of 5 years onwards. The Parental Questionnaire: Enuresis/Urinary Incontinence, the International-Consultation-on-Incontinence Questionnaire-Pediatric LUTS (ICIQ-CLUTS), as well as the Developmental Behavior Checklist for parents (DBC-P) or for adults (DBC-A) were filled out by parents or caregivers. RESULTS: 17.8% of the sample had NE, 5.9% DUI and 7.6% FI. NE was present in 44.9% of children (4-12 years), 13.5% of teens (13-17y), 3.3% of young adults (18-30y) and in 3.6% of adults (> 30y). DUI (and FI) decreased from 17.9% (21.4%) in children to 0% in adults. 3.5% of the sample had an ICIQ-CLUTS score in the clinical range. 30.5% of children and 22.1% of adults had a clinical DBC score. Children and teens with clinically relevant DBC-P-scores had significantly higher DUI rates. CONCLUSIONS: Children with WS have high rates of incontinence and LUTS, which decrease with age. Most adults are continent. NE is the most common subtype. Except for DUI in children, incontinence is not associated with behavioural problems. Screening, assessment and treatment of incontinence in individuals with WS is recommended. Neurourol. Urodynam. 35:1000-1005, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26370070 TI - Micronutrient powder distribution through Maternal, Neonatal and Child Health Weeks in Nigeria: process evaluation of feasibility and use. AB - OBJECTIVE: To determine the feasibility of distributing micronutrient powders (MNP) for home fortification during biannual Maternal, Neonatal and Child Health Week (MNCHW) events, as a strategy to improve young child nutrition. DESIGN: We evaluated the coverage, delivery, use and adherence of MNP, and associated behaviour change communication (BCC) materials and social mobilization, through cross-sectional surveys of caregivers attending health-service distribution events and health workers involved in MNP distribution, facility-based observations of MNP distribution activities and a repeated survey of caregivers in their homes who received MNP for their child. SETTING: Four Local Government Areas in Benue State, Nigeria. SUBJECTS: Caregivers of children 6-59 months of age attending health-service distribution events. RESULTS: The 8 million MNP delivered in this pilot during three distribution events were estimated to reach about one-third of eligible children in the area at each event. Programme fidelity was limited by shortages of MNP, BCC materials and inadequate social mobilization, with some limitations in health worker training and engagement. MNP use was consistent with the recommended two or three sachets per week among 51-69 % of caregivers surveyed at home. CONCLUSIONS: MNP coverage was low, but consistent with that typically achieved with other services delivered through MNCHW in Benue. Among caregivers who received MNP, acceptance and use among targeted children was high. While some weaknesses in knowledge and delivery of MNP by health workers were observed, health system strengthening and more extensive social mobilization would be key to achieving higher coverage with MNP and other health services provided through MNCHW. PMID- 26370071 TI - Cellulose degrading bacteria isolated from industrial samples and the gut of native insects from Northwest of Argentina. AB - The raw materials used to produce bioethanol mostly are food crops, which has led to conflicts on food security. It is, therefore, recommended the gradual replacement for second generation substrates such as lignocellulosic materials. Herein, cellulolytic bacteria were isolated from the gut content of native larvae from Lepidoptera, Coleoptera, and adults of Isoptera. Few environmental samples from the pulp and paper feedstock were also assessed. A total of 233 isolates were obtained using enrichment cultures and classic criteria. Interestingly, several halo-forming colonies were found to be bacterial consortia that presented difficulties to take apart the microbial members. Those pure isolates which hydrolyzed cellulose in larger extend (45 strains) were selected and identified by means of 16S rRNA sequence analysis. Firmicutes was the prevalent phylum (62.2%) being Bacillus spp. the most frequent genus, while Paenibacillus, Brevibacillus, Cohnella, and Staphylococcus species were less frequent. The phylum Actinobacteria (6.7%) was represented by isolates related to Agromyces spp. and Microbacterium spp. Regarding Gram-negative bacteria (31.1%), the more depicted genus was Pseudomonas spp., and members of Achromobacter spp., Enterobacter spp., and Bacteroidetes phylum were also selected. These native bacterial strains are expected to enlarge the cellulolytic toolbox for efficient biomass deconstruction. PMID- 26370072 TI - Changes in preschool children's OHRQoL after treatment of dental caries: responsiveness of the B-ECOHIS. AB - BACKGROUND: Oral health-related quality of life (OHRQoL) measures should be tested for responsiveness to change if they are to be used as outcomes in randomized clinical trials. AIM: To assess the responsiveness of the Brazilian ECOHIS (B-ECOHIS) to dental treatment of dental caries. METHODS: One hundred parents of 3- to 5-year-old children completed the B-ECOHIS prior to their children's treatment and 7-14 days after completion of treatment. The post treatment questionnaire also included a global transition judgment that assessed parent's perceptions of change in their children's oral health following treatment. Change scores, longitudinal construct validity, standardized effect sizes (ES) and standardized response mean (SRM) were calculated. RESULTS: Improvements in children's oral health after treatment were reflected in mean pre and post-treatment B-ECOHIS scores. They declined considerably significantly from 17.4 to 1.6 (P < 0.0001), as did the individual domain scores (P < 0.0001). There were significant differences in the pre- and post-treatment scores of children who reported little improvement (P < 0.0001) as well as in those who reported large improvements (P < 0.0001). The ES and SRM based on change scores mean for total scores and for categories of global transitions judgments were large. CONCLUSIONS: Dental treatment resulted in significant improvement of the preschool children's OHRQoL. The B-ECOHIS is responsive. PMID- 26370073 TI - Reactive oxygen species mediate Terbufos-induced apoptosis in mouse testicular cell lines via the modulation of cell cycle and pro-apoptotic proteins. AB - Terbufos (S-t-butylthiomethyl-O,O-diethyl phosphorodithioate) is a highly toxic organophosphate which is extensively used as an insecticide and nematicide. Chronic exposure to terbufos causes neuronal injury and predisposes to neurodegenerative diseases. Accumulating evidence has shown that the exposure to terbufos, as an occupational risk factor, may also cause reproductive disorders. However, the exact mechanisms of reproductive toxicity remain unclear. The present study aimed to investigate the toxic effect of terbufos on testicular cells and to explore the mechanism of toxicity on a cellular level. The cytotoxic effects of terbufos on mouse immortalized spermatogonia (GC-1), spermatocytes (GC 2), Leydig (TM3), and Sertoli (TM4) cell lines were assessed by MTT assays, caspase activation, flow cytometry, TUNEL assay, Western blot, and cell cycle analysis. The exposure to different concentrations of terbufos ranging from 50 to 800 MUM for 6 h caused significant death in all the used testicular cell lines. Terbufos increased reactive oxygen species (ROS) production, reduced mitochondrial membrane potential, and initiated apoptosis, which was confirmed by a dose-dependent increase in the number of TUNEL-positive apoptotic cells. Blocking ROS production by N-acetyl cysteine (NAC) protected GC-1 cells from terbufos-induced cell death. The results demonstrated that terbufos induces ROS, apoptosis, and DNA damage in testicular cell lines and it should be considered potentially hazardous to testis. Together, this study provided potential molecular mechanisms of terbufos-induced toxicity in testicular cells and suggests a possible protective measure. (c) 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1888-1898, 2016. PMID- 26370074 TI - Mouse Siglec-1 Mediates trans-Infection of Surface-bound Murine Leukemia Virus in a Sialic Acid N-Acyl Side Chain-dependent Manner. AB - Siglec-1 (sialoadhesin, CD169) is a surface receptor on human cells that mediates trans-enhancement of HIV-1 infection through recognition of sialic acid moieties in virus membrane gangliosides. Here, we demonstrate that mouse Siglec-1, expressed on the surface of primary macrophages in an interferon-alpha-responsive manner, captures murine leukemia virus (MLV) particles and mediates their transfer to proliferating lymphocytes. The MLV infection of primary B-cells was markedly more efficient than that of primary T-cells. The major structural protein of MLV particles, Gag, frequently co-localized with Siglec-1, and trans infection, primarily of surface-bound MLV particles, efficiently occurred. To explore the role of sialic acid for MLV trans-infection at a submolecular level, we analyzed the potential of six sialic acid precursor analogs to modulate the sialylated ganglioside-dependent interaction of MLV particles with Siglec-1. Biosynthetically engineered sialic acids were detected in both the glycolipid and glycoprotein fractions of MLV producer cells. MLV released from cells carrying N acyl-modified sialic acids displayed strikingly different capacities for Siglec-1 mediated capture and trans-infection; N-butanoyl, N-isobutanoyl, N-glycolyl, or N pentanoyl side chain modifications resulted in up to 92 and 80% reduction of virus particle capture and trans-infection, respectively, whereas N-propanoyl or N-cyclopropylcarbamyl side chains had no effect. In agreement with these functional analyses, molecular modeling indicated reduced binding affinities for non-functional N-acyl modifications. Thus, Siglec-1 is a key receptor for macrophage/lymphocyte trans-infection of surface-bound virions, and the N-acyl side chain of sialic acid is a critical determinant for the Siglec-1/MLV interaction. PMID- 26370076 TI - Self-assembly is prerequisite for catalysis of Fe(II) oxidation by catalytically active subunits of ferritin. AB - Fe(III) storage by ferritin is an essential process of the iron homeostasis machinery. It begins by translocation of Fe(II) from outside the hollow spherical shape structure of the protein, which is formed as the result of self-assembly of 24 subunits, to a di-iron binding site, the ferroxidase center, buried in the middle of each active subunit. The pathway of Fe(II) to the ferroxidase center has remained elusive, and the importance of self-assembly for the functioning of the ferroxidase center has not been investigated. Here we report spectroscopic and metal ion binding studies with a mutant of ferritin from Pyrococcus furiosus (PfFtn) in which self-assembly was abolished by a single amino acid substitution. We show that in this mutant metal ion binding to the ferroxidase center and Fe(II) oxidation at this site was obliterated. However, metal ion binding to a conserved third site (site C), which is located in the inner surface of each subunit in the vicinity of the ferroxidase center and is believed to be the path for Fe(II) to the ferroxidase center, was not disrupted. These results are the basis of a new model for Fe(II) translocation to the ferroxidase center: self assembly creates channels that guide the Fe(II) ions toward the ferroxidase center directly through the protein shell and not via the internal cavity and site C. The results may be of significance for understanding the molecular basis of ferritin-related disorders such as neuroferritinopathy in which the 24-meric structure with 432 symmetry is distorted. PMID- 26370075 TI - Streptococcus pneumoniae NanC: STRUCTURAL INSIGHTS INTO THE SPECIFICITY AND MECHANISM OF A SIALIDASE THAT PRODUCES A SIALIDASE INHIBITOR. AB - Streptococcus pneumoniae is an important human pathogen that causes a range of disease states. Sialidases are important bacterial virulence factors. There are three pneumococcal sialidases: NanA, NanB, and NanC. NanC is an unusual sialidase in that its primary reaction product is 2-deoxy-2,3-didehydro-N-acetylneuraminic acid (Neu5Ac2en, also known as DANA), a nonspecific hydrolytic sialidase inhibitor. The production of Neu5Ac2en from alpha2-3-linked sialosides by the catalytic domain is confirmed within a crystal structure. A covalent complex with 3-fluoro-beta-N-acetylneuraminic acid is also presented, suggesting a common mechanism with other sialidases up to the final step of product formation. A conformation change in an active site hydrophobic loop on ligand binding constricts the entrance to the active site. In addition, the distance between the catalytic acid/base (Asp-315) and the ligand anomeric carbon is unusually short. These features facilitate a novel sialidase reaction in which the final step of product formation is direct abstraction of the C3 proton by the active site aspartic acid, forming Neu5Ac2en. NanC also possesses a carbohydrate-binding module, which is shown to bind alpha2-3- and alpha2-6-linked sialosides, as well as N-acetylneuraminic acid, which is captured in the crystal structure following hydration of Neu5Ac2en by NanC. Overall, the pneumococcal sialidases show remarkable mechanistic diversity while maintaining a common structural scaffold. PMID- 26370077 TI - A kissing loop is important for btuB riboswitch ligand sensing and regulatory control. AB - RNA-based genetic regulation is exemplified by metabolite-binding riboswitches that modulate gene expression through conformational changes. Crystal structures show that the Escherichia coli btuB riboswitch contains a kissing loop interaction that is in close proximity to the bound ligand. To analyze the role of the kissing loop interaction in the riboswitch regulatory mechanism, we used RNase H cleavage assays to probe the structure of nascent riboswitch transcripts produced by the E. coli RNA polymerase. By monitoring the folding of the aptamer, kissing loop, and riboswitch expression platform, we established the conformation of each structural component in the absence or presence of bound adenosylcobalamin. We found that the kissing loop interaction is not essential for ligand binding. However, we showed that kissing loop formation improves ligand binding efficiency and is required to couple ligand binding to the riboswitch conformational changes involved in regulating gene expression. These results support a mechanism by which the btuB riboswitch modulates the formation of a tertiary structure to perform metabolite sensing and regulate gene expression. PMID- 26370078 TI - Resistance of Dynamin-related Protein 1 Oligomers to Disassembly Impairs Mitophagy, Resulting in Myocardial Inflammation and Heart Failure. AB - We have reported previously that a missense mutation in the mitochondrial fission gene Dynamin-related protein 1 (Drp1) underlies the Python mouse model of monogenic dilated cardiomyopathy. The aim of this study was to investigate the consequences of the C452F mutation on Drp1 protein function and to define the cellular sequelae leading to heart failure in the Python monogenic dilated cardiomyopathy model. We found that the C452F mutation increased Drp1 GTPase activity. The mutation also conferred resistance to oligomer disassembly by guanine nucleotides and high ionic strength solutions. In a mouse embryonic fibroblast model, Drp1 C452F cells exhibited abnormal mitochondrial morphology and defective mitophagy. Mitochondria in C452F mouse embryonic fibroblasts were depolarized and had reduced calcium uptake with impaired ATP production by oxidative phosphorylation. In the Python heart, we found a corresponding progressive decline in oxidative phosphorylation with age and activation of sterile inflammation. As a corollary, enhancing autophagy by exposure to a prolonged low-protein diet improved cardiac function in Python mice. In conclusion, failure of Drp1 disassembly impairs mitophagy, leading to a downstream cascade of mitochondrial depolarization, aberrant calcium handling, impaired ATP synthesis, and activation of sterile myocardial inflammation, resulting in heart failure. PMID- 26370079 TI - Activation of Toll-like receptor 4 (TLR4) attenuates adaptive thermogenesis via endoplasmic reticulum stress. AB - Adaptive thermogenesis is the cellular process transforming chemical energy into heat in response to cold. A decrease in adaptive thermogenesis is a contributing factor to obesity. However, the molecular mechanisms responsible for the compromised adaptive thermogenesis in obese subjects have not yet been elucidated. In this study we hypothesized that Toll-like receptor 4 (TLR4) activation and subsequent inflammatory responses are key regulators to suppress adaptive thermogenesis. To test this hypothesis, C57BL/6 mice were either fed a palmitate-enriched high fat diet or administered with chronic low-dose LPS before cold acclimation. TLR4 stimulation by a high fat diet or LPS were both associated with reduced core body temperature and heat release. Impairment of thermogenic activation was correlated with diminished expression of brown-specific markers and mitochondrial dysfunction in subcutaneous white adipose tissue (sWAT). Defective sWAT browning was concomitant with elevated levels of endoplasmic reticulum (ER) stress and autophagy. Consistently, TLR4 activation by LPS abolished cAMP-induced up-regulation of uncoupling protein 1 (UCP1) in primary human adipocytes, which was reversed by silencing of C/EBP homologous protein (CHOP). Moreover, the inactivation of ER stress by genetic deletion of CHOP or chemical chaperone conferred a resistance to the LPS-induced suppression of adaptive thermogenesis. Collectively, our data indicate the existence of a novel signaling network that links TLR4 activation, ER stress, and mitochondrial dysfunction, thereby antagonizing thermogenic activation of sWAT. Our results also suggest that TLR4/ER stress axis activation may be a responsible mechanism for obesity-mediated defective brown adipose tissue activation. PMID- 26370080 TI - Effect of cholesterol reduction on receptor signaling in neurons. AB - Diabetes mellitus is associated with a variety of complications, including alterations in the central nervous system (CNS). We have recently shown that diabetes results in a reduction of cholesterol synthesis in the brain due to decreased insulin stimulation of SREBP2-mediated cholesterol synthesis in neuronal and glial cells. In the present study, we explored the effects of the decrease in cholesterol on neuronal cell function using GT1-7 hypothalamic cells subjected to cholesterol depletion in vitro using three independent methods: 1) exposure to methyl-beta-cyclodextrin, 2) treatment with the HMG-CoA reductase inhibitor simvastatin, and 3) shRNA-mediated knockdown of SREBP2. All three methods produced 20-31% reductions in cellular cholesterol content, similar to the decrease in cholesterol synthesis observed in diabetes. All cholesterol depleted neuron-derived cells, independent of the method of reduction, exhibited decreased phosphorylation/activation of IRS-1 and AKT following stimulation by insulin, insulin-like growth factor-1, or the neurotrophins (NGF and BDNF). ERK phosphorylation/activation was also decreased after methyl-beta-cyclodextrin and statin treatment but increased in cells following SREBP2 knockdown. In addition, apoptosis in the presence of amyloid-beta was increased. Reduction in cellular cholesterol also resulted in increased basal autophagy and impairment of induction of autophagy by glucose deprivation. Together, these data indicate that a reduction in neuron-derived cholesterol content, similar to that observed in diabetic brain, creates a state of insulin and growth factor resistance that could contribute to CNS-related complications of diabetes, including increased risk of neurodegenerative diseases, such as Alzheimer disease. PMID- 26370081 TI - Robust glyoxalase activity of Hsp31, a ThiJ/DJ-1/PfpI family member protein, is critical for oxidative stress resistance in Saccharomyces cerevisiae. AB - Methylglyoxal (MG) is a reactive metabolic intermediate generated during various cellular biochemical reactions, including glycolysis. The accumulation of MG indiscriminately modifies proteins, including important cellular antioxidant machinery, leading to severe oxidative stress, which is implicated in multiple neurodegenerative disorders, aging, and cardiac disorders. Although cells possess efficient glyoxalase systems for detoxification, their functions are largely dependent on the glutathione cofactor, the availability of which is self-limiting under oxidative stress. Thus, higher organisms require alternate modes of reducing the MG-mediated toxicity and maintaining redox balance. In this report, we demonstrate that Hsp31 protein, a member of the ThiJ/DJ-1/PfpI family in Saccharomyces cerevisiae, plays an indispensable role in regulating redox homeostasis. Our results show that Hsp31 possesses robust glutathione-independent methylglyoxalase activity and suppresses MG-mediated toxicity and ROS levels as compared with another paralog, Hsp34. On the other hand, glyoxalase-defective mutants of Hsp31 were found highly compromised in regulating the ROS levels. Additionally, Hsp31 maintains cellular glutathione and NADPH levels, thus conferring protection against oxidative stress, and Hsp31 relocalizes to mitochondria to provide cytoprotection to the organelle under oxidative stress conditions. Importantly, human DJ-1, which is implicated in the familial form of Parkinson disease, complements the function of Hsp31 by suppressing methylglyoxal and oxidative stress, thus signifying the importance of these proteins in the maintenance of ROS homeostasis across phylogeny. PMID- 26370082 TI - AMP-activated protein kinase stimulates Warburg-like glycolysis and activation of satellite cells during muscle regeneration. AB - Satellite cells are the major myogenic stem cells residing inside skeletal muscle and are indispensable for muscle regeneration. Satellite cells remain largely quiescent but are rapidly activated in response to muscle injury, and the derived myogenic cells then fuse to repair damaged muscle fibers or form new muscle fibers. However, mechanisms eliciting metabolic activation, an inseparable step for satellite cell activation following muscle injury, have not been defined. We found that a noncanonical Sonic Hedgehog (Shh) pathway is rapidly activated in response to muscle injury, which activates AMPK and induces a Warburg-like glycolysis in satellite cells. AMPKalpha1 is the dominant AMPKalpha isoform expressed in satellite cells, and AMPKalpha1 deficiency in satellite cells impairs their activation and myogenic differentiation during muscle regeneration. Drugs activating noncanonical Shh promote proliferation of satellite cells, which is abolished because of satellite cell-specific AMPKalpha1 knock-out. Taken together, AMPKalpha1 is a critical mediator linking noncanonical Shh pathway to Warburg-like glycolysis in satellite cells, which is required for satellite activation and muscle regeneration. PMID- 26370083 TI - Structural Basis for a Unique ATP Synthase Core Complex from Nanoarcheaum equitans. AB - ATP synthesis is a critical and universal life process carried out by ATP synthases. Whereas eukaryotic and prokaryotic ATP synthases are well characterized, archaeal ATP synthases are relatively poorly understood. The hyperthermophilic archaeal parasite, Nanoarcheaum equitans, lacks several subunits of the ATP synthase and is suspected to be energetically dependent on its host, Ignicoccus hospitalis. This suggests that this ATP synthase might be a rudimentary machine. Here, we report the crystal structures and biophysical studies of the regulatory subunit, NeqB, the apo-NeqAB, and NeqAB in complex with nucleotides, ADP, and adenylyl-imidodiphosphate (non-hydrolysable analog of ATP). NeqB is ~20 amino acids shorter at its C terminus than its homologs, but this does not impede its binding with NeqA to form the complex. The heterodimeric NeqAB complex assumes a closed, rigid conformation irrespective of nucleotide binding; this differs from its homologs, which require conformational changes for catalytic activity. Thus, although N. equitans possesses an ATP synthase core A3B3 hexameric complex, it might not function as a bona fide ATP synthase. PMID- 26370084 TI - Structural and Functional Insights into the Cryoprotection of Membranes by the Intrinsically Disordered Dehydrins. AB - Dehydration can be due to desiccation caused by a lack of environmental water or to freezing caused by a lack of liquid water. Plants have evolved a large family of proteins called LEA (late embryogenesis abundant) proteins, which include the intrinsically disordered dehydrin (dehydration protein) family, to combat these abiotic stresses. Although transcription and translation studies have shown a correlation between dehydration stress and the presence of dehydrins, the biochemical mechanisms have remained somewhat elusive. We examine here the effect and structure of a small model dehydrin (Vitis riparia K2) on the protection of membranes from freeze-thaw stress. This protein is able to bind to liposomes containing phosphatidic acid and protect the liposomes from fusing after freeze thaw treatment. The presence of K2 did not measurably affect liposome surface accessibility or lipid mobility but did lower its membrane transition temperature by 3 degrees C. Using sodium dodecyl sulfate as a membrane model, we examined the NMR structure of K2 in the presence and absence of the micelle. Biochemical and NMR experiments show that the conserved, lysine-rich segments are involved in the binding of the dehydrin to a membrane, whereas the poorly conserved phi segments play no role in binding or protection. PMID- 26370085 TI - Mechanism of cAMP Partial Agonism in Protein Kinase G (PKG). AB - Protein kinase G (PKG) is a major receptor of cGMP and controls signaling pathways often distinct from those regulated by cAMP. Hence, the selective activation of PKG by cGMP versus cAMP is critical. However, the mechanism of cGMP versus-cAMP selectivity is only limitedly understood. Although the C-terminal cyclic nucleotide-binding domain B of PKG binds cGMP with higher affinity than cAMP, the intracellular concentrations of cAMP are typically higher than those of cGMP, suggesting that the cGMP-versus-cAMP selectivity of PKG is not controlled uniquely through affinities. Here, we show that cAMP is a partial agonist for PKG, and we elucidate the mechanism for cAMP partial agonism through the comparative NMR analysis of the apo, cGMP-, and cAMP-bound forms of the PKG cyclic nucleotide-binding domain B. We show that although cGMP activation is adequately explained by a two-state conformational selection model, the partial agonism of cAMP arises from the sampling of a third, partially autoinhibited state. PMID- 26370086 TI - ELL Protein-associated Factor 2 (EAF2) Inhibits Transforming Growth Factor beta Signaling through a Direct Interaction with Smad3. AB - A series of in vitro and in vivo studies has shown that EAF2 can affect multiple signaling pathways involved in cellular processes. However, the molecular mechanisms underlying its effects have remained elusive. Here we report the discovery of a new functional link between EAF2 and TGF-beta signaling. Promoter reporter assays indicated that EAF2 suppresses Smad3 transcriptional activity, resulting in inhibition of TGF-beta signaling. Coimmunoprecipitation assays showed that EAF2 specifically interacts with Smad3 in vitro and in vivo but not with other Smad proteins. In addition, we observed that EAF2 binding does not alter Smad3 phosphorylation but causes Smad3 cytoplasmic retention, competes with Smad4 for binding to Smad3, and prevents p300-Smad3 complex formation. Furthermore, we demonstrated that EAF2 suppresses both TGF-beta-induced G1 cell cycle arrest and TGF-beta-induced cell migration. This study identifies and characterizes a novel repressor of TGF-beta signaling. PMID- 26370087 TI - Posttranslational Regulation of Human DNA Polymerase iota. AB - Human DNA polymerases (pols) eta and iota are Y-family DNA polymerase paralogs that facilitate translesion synthesis past damaged DNA. Both poleta and poliota can be monoubiquitinated in vivo. Poleta has been shown to be ubiquitinated at one primary site. When this site is unavailable, three nearby lysines may become ubiquitinated. In contrast, mass spectrometry analysis of monoubiquitinated poliota revealed that it is ubiquitinated at over 27 unique sites. Many of these sites are localized in different functional domains of the protein, including the catalytic polymerase domain, the proliferating cell nuclear antigen-interacting region, the Rev1-interacting region, and its ubiquitin binding motifs UBM1 and UBM2. Poliota monoubiquitination remains unchanged after cells are exposed to DNA damaging agents such as UV light (generating UV photoproducts), ethyl methanesulfonate (generating alkylation damage), mitomycin C (generating interstrand cross-links), or potassium bromate (generating direct oxidative DNA damage). However, when exposed to naphthoquinones, such as menadione and plumbagin, which cause indirect oxidative damage through mitochondrial dysfunction, poliota becomes transiently polyubiquitinated via Lys(11)- and Lys(48)-linked chains of ubiquitin and subsequently targeted for degradation. Polyubiquitination does not occur as a direct result of the perturbation of the redox cycle as no polyubiquitination was observed after treatment with rotenone or antimycin A, which both inhibit mitochondrial electron transport. Interestingly, polyubiquitination was observed after the inhibition of the lysine acetyltransferase KATB3/p300. We hypothesize that the formation of polyubiquitination chains attached to poliota occurs via the interplay between lysine acetylation and ubiquitination of ubiquitin itself at Lys(11) and Lys(48) rather than oxidative damage per se. PMID- 26370088 TI - Two hydrophobic residues can determine the specificity of mitogen-activated protein kinase docking interactions. AB - MAPKs bind to many of their upstream regulators and downstream substrates via a short docking motif (the D-site) on their binding partner. MAPKs that are in different families (e.g. ERK, JNK, and p38) can bind selectively to D-sites in their authentic substrates and regulators while discriminating against D-sites in other pathways. Here we demonstrate that the short hydrophobic region at the distal end of the D-site plays a critical role in determining the high selectivity of JNK MAPKs for docking sites in their cognate MAPK kinases. Changing just 1 or 2 key hydrophobic residues in this submotif is sufficient to turn a weak JNK-binding D-site into a strong one, or vice versa. These specificity-determining differences are also found in the D-sites of the ETS family transcription factors Elk-1 and Net. Moreover, swapping two hydrophobic residues between these D-sites switches the relative efficiency of Elk-1 and Net as substrates for ERK versus JNK, as predicted. These results provide new insights into docking specificity and suggest that this specificity can evolve rapidly by changes to just 1 or 2 amino acids. PMID- 26370089 TI - Pore hydration states of KcsA potassium channels in membranes. AB - Water-filled hydrophobic cavities in channel proteins serve as gateways for transfer of ions across membranes, but their properties are largely unknown. We determined water distributions along the conduction pores in two tetrameric channels embedded in lipid bilayers using neutron diffraction: potassium channel KcsA and the transmembrane domain of M2 protein of influenza A virus. For the KcsA channel in the closed state, the distribution of water is peaked in the middle of the membrane, showing water in the central cavity adjacent to the selectivity filter. This water is displaced by the channel blocker tetrabutyl ammonium. The amount of water associated with the channel was quantified, using neutron diffraction and solid state NMR. In contrast, the M2 proton channel shows a V-shaped water profile across the membrane, with a narrow constriction at the center, like the hourglass shape of its internal surface. These two types of water distribution are therefore very different in their connectivity to the bulk water. The water and protein profiles determined here provide important evidence concerning conformation and hydration of channels in membranes and the potential role of pore hydration in channel gating. PMID- 26370090 TI - WNT10B enhances proliferation through beta-catenin and RAC1 GTPase in human corneal endothelial cells. AB - The cornea is the anterior, transparent tissue of the human eye that serves as its main refractive element. Corneal endothelial cells are arranged as a monolayer on the posterior surface of the cornea and function as a pump to counteract the leakiness of its basement membrane. Maintaining the cornea in a slightly dehydrated state is critical for the maintenance of corneal transparency. Adult human corneal endothelial cells are G1-arrested, even in response to injury, leading to an age-dependent decline in endothelial cell density. Corneal edema and subsequent vision loss ensues when endothelial cell density decreases below a critical threshold. Vision loss secondary to corneal endothelial dysfunction is a common indication for transplantation in developed nations. An impending increase in demand for and a current global shortage of donor corneas will necessitate the development of treatments for vision loss because of endothelial dysfunction that do not rely on donor corneas. Wnt ligands regulate many critical cellular functions, such as proliferation, making them attractive candidates for modulation in corneal endothelial dysfunction. We show that WNT10B causes nuclear transport and binding of RAC1 and beta-catenin in human corneal endothelial cells, leading to the activation of Cyclin D1 expression and proliferation. Our findings indicate that WNT10B promotes proliferation in human corneal endothelial cells by simultaneously utilizing both beta-catenin-dependent and -independent pathways and suggest that its modulation could be used to treat vision loss secondary to corneal endothelial dysfunction. PMID- 26370091 TI - Kinetic contributions to gating by interactions unique to N-methyl-D-aspartate (NMDA) receptors. AB - Among glutamate-gated channels, NMDA receptors produce currents that subside with unusually slow kinetics, and this feature is essential to the physiology of central excitatory synapses. Relative to the homologous AMPA and kainate receptors, NMDA receptors have additional intersubunit contacts in the ligand binding domain that occur at both conserved and non-conserved sites. We examined GluN1/GluN2A single-channel currents with kinetic analyses and modeling to probe these class-specific intersubunit interactions for their role in glutamate binding and receptor gating. We found that substitutions that eliminate such interactions at non-conserved sites reduced stationary gating, accelerated deactivation, and imparted sensitivity to aniracetam, an AMPA receptor-selective positive modulator. Abolishing unique contacts at conserved sites also reduced stationary gating and accelerated deactivation. These results show that contacts specific to NMDA receptors, which brace the heterodimer interface within the ligand binding domain, stabilize actively gating receptor conformations and result in longer bursts and slower deactivations. They support the view that the strength of the heterodimer interface modulates gating in both NMDA and non-NMDA receptors and that unique interactions at this interface are responsible in part for basic differences between the kinetics of NMDA and non-NMDA currents at glutamatergic synapses. PMID- 26370092 TI - Structural Insights into the Assembly of the Adeno-associated Virus Type 2 Rep68 Protein on the Integration Site AAVS1. AB - Adeno-associated virus (AAV) is the only eukaryotic virus with the property of establishing latency by integrating site-specifically into the human genome. The integration site known as AAVS1 is located in chromosome 19 and contains multiple GCTC repeats that are recognized by the AAV non-structural Rep proteins. These proteins are multifunctional, with an N-terminal origin-binding domain (OBD) and a helicase domain joined together by a short linker. As a first step to understand the process of site-specific integration, we proceeded to characterize the recognition and assembly of Rep68 onto the AAVS1 site. We first determined the x-ray structure of AAV-2 Rep68 OBD in complex with the AAVS1 DNA site. Specificity is achieved through the interaction of a glycine-rich loop that binds the major groove and an alpha-helix that interacts with a downstream minor groove on the same face of the DNA. Although the structure shows a complex with three OBD molecules bound to the AAVS1 site, we show by using analytical centrifugation and electron microscopy that the full-length Rep68 forms a heptameric complex. Moreover, we determined that a minimum of two direct repeats is required to form a stable complex and to melt DNA. Finally, we show that although the individual domains bind DNA poorly, complex assembly requires oligomerization and cooperation between its OBD, helicase, and the linker domains. PMID- 26370093 TI - Evidence- and consensus-based (S3) Guidelines for the Treatment of Actinic Keratosis - International League of Dermatological Societies in cooperation with the European Dermatology Forum - Short version. AB - BACKGROUND: Actinic keratosis (AK) is a frequent health condition attributable to chronic exposure to ultraviolet radiation. Several treatment options are available and evidence based guidelines are missing. OBJECTIVES: The goal of these evidence- and consensus-based guidelines was the development of treatment recommendations appropriate for different subgroups of patients presenting with AK. A secondary aim of these guidelines was the implementation of knowledge relating to the clinical background of AK, including consensus-based recommendations for the histopathological definition, diagnosis and the assessment of patients. METHODS: The guidelines development followed a pre defined and structured process. For the underlying systematic literature review of interventions for AK, the methodology suggested by the Cochrane Handbook for Systematic Reviews of Interventions, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was adapted. All recommendations were consented during a consensus conference using a formal consensus methodology. Strength of recommendations was expressed based on the GRADE approach. If expert opinion without external evidence was incorporated into the reasoning for making a certain recommendation, the rationale was provided. The Guidelines underwent open public review and approval by the commissioning societies. RESULTS: Various interventions for the treatment of AK have been assessed for their efficacy. The consenting procedure led to a treatment algorithm as shown in the guidelines document. Based on expert consensus, the present guidelines present recommendations on the classification of patients, diagnosis and histopathological definition of AK. Details on the methods and results of the systematic literature review and guideline development process have been published separately. CONCLUSIONS: International guidelines are intended to be adapted to national or regional circumstances (regulatory approval, availability and reimbursement of treatments). PMID- 26370094 TI - Comparison of the ability of two continuous cardiac output monitors to measure trends in cardiac output: estimated continuous cardiac output measured by modified pulse wave transit time and an arterial pulse contour-based cardiac output device. AB - Estimated continuous cardiac output (esCCO), a noninvasive technique for continuously measuring cardiac output (CO), is based on modified pulse wave transit time, which in turn is determined by pulse oximetry and electrocardiography. However, its trending ability has never been evaluated in patients undergoing non-cardiac surgery. Therefore, this study examined esCCO's ability to detect the exact changes in CO, compared with currently available arterial waveform analysis methods, in patients undergoing kidney transplantation. CO was measured using an esCCO system and arterial pressure based CO (APCO), and compared with a corresponding intermittent bolus thermodilution CO (ICO) method. Percentage error and statistical methods, including concordance analysis and polar plot analysis, were used to analyze results from 15 adult patients. The difference in the CO values between esCCO and ICO was -0.39 +/- 1.15 L min(-1) (percentage error, 35.6 %). And corrected precision for repeated measures was 1.16 L min(-1) (percentage error for repeated measures, 36.0 %). A concordance analysis showed that the concordance rate was 93.1 %. The mean angular bias was -1.8 degrees and the radial limits of agreement were +/-37.6 degrees . The difference between the APCO and ICO CO values was 0.04 +/- 1.37 L min(-1) (percentage error, 42.4 %). And corrected precision for repeated measures was 1.37 L min(-1) (percentage error for repeated measures, 42.5 %). The concordance rate was 89.7 %, with a mean angular bias of 3.3 degrees and radial limits of agreement of +/-42.2 degrees . This study demonstrated that the trending ability of the esCCO system is not clinically acceptable, as judged by polar plots analysis; however, its trending ability is clinically acceptable based on a concordance analysis, and is comparable with currently available arterial waveform analysis methods. PMID- 26370095 TI - Are financial incentives cost-effective to support smoking cessation during pregnancy? AB - AIMS: To investigate the cost-effectiveness of up to L400 worth of financial incentives for smoking cessation in pregnancy as an adjunct to routine health care. DESIGN: Cost-effectiveness analysis based on a Phase II randomized controlled trial (RCT) and a cost-utility analysis using a life-time Markov model. SETTING: The RCT was undertaken in Glasgow, Scotland. The economic analysis was undertaken from the UK National Health Service (NHS) perspective. PARTICIPANTS: A total of 612 pregnant women randomized to receive usual cessation support plus or minus financial incentives of up to L400 vouchers (US $609), contingent upon smoking cessation. MEASUREMENTS: Comparison of usual support and incentive interventions in terms of cotinine-validated quitters, quality-adjusted life years (QALYs) and direct costs to the NHS. FINDINGS: The incremental cost per quitter at 34-38 weeks pregnant was L1127 ($1716).This is similar to the standard look-up value derived from Stapleton & West's published ICER tables, L1390 per quitter, by looking up the Cessation in Pregnancy Incentives Trial (CIPT) incremental cost (L157) and incremental 6-month quit outcome (0.14). The life-time model resulted in an incremental cost of L17 [95% confidence interval (CI) = -L93, L107] and a gain of 0.04 QALYs (95% CI = -0.058, 0.145), giving an ICER of L482/QALY ($734/QALY). Probabilistic sensitivity analysis indicates uncertainty in these results, particularly regarding relapse after birth. The expected value of perfect information was L30 million (at a willingness to pay of L30 000/QALY), so given current uncertainty, additional research is potentially worthwhile. CONCLUSION: Financial incentives for smoking cessation in pregnancy are highly cost-effective, with an incremental cost per quality-adjusted life years of L482, which is well below recommended decision thresholds. PMID- 26370096 TI - [Narrow band imaging-assisted cystoscopy in bladder tumor follow-up: Can more tumors be identified?]. AB - BACKGROUND: Narrow band imaging (NBI) is a new technique of urethrocystoscopy, in which only certain wavelengths [415 (blue) and 540 nm (green)] are used to detect urothelial carcinoma. The aim of the investigation was to analyze the potential benefit of NBI in the follow-up of patients with transitional cell carcinoma of the bladder. METHODS: Between August 2013 and July 2014, patients with a history of transitional cell carcinoma of the bladder, presenting for follow-up cystoscopy, were either examined via flexible white light endoscopy (WLE) plus second look WLE (n = 251, controls) or second look NBI cystoscopy alone (n = 251) in the same session. RESULTS: Rates of recurrences were similar in the two groups [NBI 68 (27.1 %); WLE 70 (27.9 %)]. NBI after WLE identified more tumors in 13 patients (5.69 vs. 3.92). In 8 patients NBI showed no vascularization in suspicious areas. In the control arm, in 8 cases more tumors (3.75 vs. 3.13) were identified in the second WLE. CONCLUSIONS: The additional use of NBI in the follow-up cystoscopy of patients after transurethral resection of nonmuscle invasive bladder cancer leads to an increased number of detected tumors; however, a part of the additionally detected tumors can be explained by the double examination. NBI appears to provide information in individual cases whether transurethral resection of bladder tumor is necessary. PMID- 26370097 TI - Extremely low frequency electromagnetic field sensitizes cisplatin-resistant human ovarian adenocarcinoma cells via P53 activation. AB - In the following study, extremely low frequency electromagnetic fields (EL-EMF) radiation was used to restore sensitivity in the cisplatin-resistant A2780 ovarian cancer cells. For this purpose A2780 cells were treated with different doses of cisplatin and EL-EMF (50 Hz, 200 gauss, and 2 h) alone. Cytotoxicity was the measurement using MTT assay. After calculating IC50 for cisplatin (90 ug/ml) a lower concentration from IC50 (30 and 60 ug/ml) was used to be combined with EL EMF. We compare the effects of each cisplatin, EL-EMF and combination groups using acridine orange-propidium iodide (AO/PI) and DAPI staining, caspase 3/9 activation assay and Annexin/PI assay. We also assessed changes in P53 and Matrix metalloproteinases 2 (MMPs) gene expression with semi-quantitative RT-PCR. Results indicated an EL-EMF-dependent proliferative decrease which was found <10 %, and occurred independently of cisplatin. The decreased proliferation rate for 30 and 60 ug/ml cisplatin was about 20 and 40 %, respectively, while for synergistic groups 30 and 60 ug/ml cisplatin with 2 h EL-EMF exposer, showed 47 and 71 % decrease in viability in rats. DAPI staining indicated that chromatin break down significantly increased in synergistic groups. Acridine orange staining also confirmed MTT assay results. Caspase activity significantly increased in the combined groups. Semi-quantitative RT-PCR showed that in synergistic groups of cisplatin and EL-EMF, expression of P53 was increased but the expression level of MPP-2 gene decreased. Results from this study showed that changes generated by the non-invasive EL-EMF can make resistant cells sensitive to cisplatin. PMID- 26370098 TI - Evaluating a new methodology for providing individualized feedback in healthcare on quality of life and its importance, using the WHOQOL-BREF in a community population. AB - PURPOSE: We conducted an evaluation to find out how a novel quality of life (QoL) intervention containing guided individualized feedback was appraised. The importance of QoL was matched with QoL assessment for each subjective dimension, using graphical feedback. We examined whether this information was acceptable, feasible and valued beyond the clinical context, among the community. METHODS: Using a mixed-methods cross-sectional design, the intervention was piloted with 129 participants from communities and registered in primary care. WHOQOL-BREF and WHOQOL Importance scores were graphically matched by dimension. Results were inspected and interpreted with directed guidance to identify good and poor QoL. We report the post-intervention evaluation of feedback, including qualitative themes. Follow-up interviews among those expecting feedback to be helpful explored potential self-management and healthcare uses. RESULTS: After feedback, 65 % reported changes in thoughts and perceptions of QoL, often describing insights as self-affirming. Goals or expectations changed for 34 %, and motivation to change was reported. Over 50 % evaluated the feedback as helpful in the short term or for the future. Follow-up interviews endorsed the value of the feedback and its usefulness in sharing with a healthcare professional (92 %), suggesting it would facilitate professionals' understandings of patients and enable health advice to be targeted. CONCLUSIONS: The benefits of using this novel feedback can be extended to the general population, as directed guidance aids interpretation, thereby saving health service costs. This complex pilot intervention needs testing in a blinded fully randomized controlled trial. Beyond independent self-management, graphs could be used during clinical decision making. PMID- 26370099 TI - The application of a network approach to Health-Related Quality of Life (HRQoL): introducing a new method for assessing HRQoL in healthy adults and cancer patients. AB - PURPOSE: Health-Related Quality of Life (HRQoL) research has typically adopted either a formative approach, in which HRQoL is the common effect of its observables, or a reflective approach--defining HRQoL as a latent variable that determines observable characteristics of HRQoL. Both approaches, however, do not take into account the complex organization of these characteristics. The objective of this study was to introduce a new approach for analyzing HRQoL data, namely a network model (NM). An NM, as opposed to traditional research strategies, accounts for interactions among observables and offers a complementary analytic approach. METHODS: We applied the NM to samples of Dutch cancer patients (N = 485) and Dutch healthy adults (N = 1742) who completed the 36-item Short Form Health Survey (SF-36). Networks were constructed for both samples separately and for a combined sample with diagnostic status added as an extra variable. We assessed the network structures and compared the structures of the two separate samples on the item and domain levels. The relative importance of individual items in the network structures was determined using centrality analyses. RESULTS: We found that the global structure of the SF-36 is dominant in all networks, supporting the validity of questionnaire's subscales. Furthermore, results suggest that the network structure of both samples was highly similar. Centrality analyses revealed that maintaining a daily routine despite one's physical health predicts HRQoL levels best. CONCLUSIONS: We concluded that the NM provides a fruitful alternative to classical approaches used in the psychometric analysis of HRQoL data. PMID- 26370101 TI - A SWOT Analysis of the Updated National HIV/AIDS Strategy for the U.S., 2015 2020. AB - In July 2015, President Barack Obama released an updated National HIV/AIDS Strategy (NHAS) for the United States to guide HIV efforts through the year 2020. A federal action plan to accompany the updated NHAS will be released in December 2015. In this editorial, we offer a strengths, weaknesses, opportunities and threats analysis with the aim of increasing discussion of ways to truly fulfill the promise of the updated NHAS and to address barriers that may thwart it from achieving its full potential. PMID- 26370100 TI - Cocaine Use May be Associated with Increased Depression in Persons Infected with HIV. AB - HIV infection, depression, and cocaine use are independently associated with increased inflammatory signal production. There is increasing evidence about the role of inflammation in depression. In HIV disease, cocaine use may increase disease progression as well as alter T cell functioning resulting in cytokine activation and thereby increasing susceptibility to depression. We examined the association between cocaine use and depression among 447 African American persons infected with HIV who were frequent cocaine users or non-users, enrolled in an observational study in Baltimore, Maryland, between August 2003 and December 2012. The overall prevalence of depression was 40.9 % (183 of 447) participants. Among persons who were depressed, the prevalence of cocaine use was 81.4 % (149 of 183), compared to 69.3 % among persons who were not depressed (183 of 264), P = 0.004. Cocaine use was associated with nearly twofold increased odds of depression, unadjusted odds ratio (OR) 1.94, (95 % CI 1.23, 3.06); P = 0.004, compared to never using cocaine, and OR 1.02, (95 % CI 1.10, 1.05); P = 0.04 in adjusted analysis. A dose-response relationship between increasing duration of cocaine use and depression was observed. Frequency and duration of cocaine use may be associated with depression. We speculate that depression among cocaine users with HIV may involve an inflammatory component that needs further examination. PMID- 26370102 TI - Acute Effects on the Counts of Innate and Adaptive Immune Response Cells After 1 Month of Taoist Qigong Practice. AB - BACKGROUND: Qigong is an ancient form of health maintenance, dating back thousands of years, which is part of Traditional Chinese Medicine. Numerous physical as well as mental benefits have been classically ascribed to this traditional mind-body method which integrates slow body movements, breathing, and meditation. Albeit we have already reported an immunomodulatory action of qigong in other investigations, measures were then assessed 1 day after the qigong program ended. PURPOSE: The aim of the present study was to assess the acute effects of Taoist qigong practice on immune cell counts in healthy subjects 1 h after training. METHOD: Forty-three healthy subjects participated in the study of whom 25 were randomly allocated to the experimental group and 18 to the control group. The experimental subjects underwent daily qigong training for 1 month. Blood samples for the quantification of immune parameters (number and percentage of monocytes, neutrophils, eosinophils, total lymphocytes, B lymphocytes, and natural killer (NK) cells) were taken the day before the experiment commenced and 1 h after the last session of the training program ended. As statistical analysis, analysis of covariance (ANCOVA) was performed. RESULTS: Statistically significant differences were found between the experimental and control groups, with the experimental group showing higher values in the number (p = 0.006) and the percentage (p = 0.04) of B lymphocytes, as well as lower values in the percentage of NK cells (p = 0.05), as compared to control. CONCLUSION: This study demonstrates that Taoist qigong is able to exert acute immunomodulatory effects on components of both innate as well as adaptive immune response. PMID- 26370103 TI - Metabolic syndrome in Sjogren's syndrome patients: a relevant concern for clinical monitoring. AB - Metabolic syndrome (MetS) has been described in autoimmune diseases. However, there are scarce data about MetS and adipocytokine profile in primary Sjogren's syndrome (pSS). Seventy-one female pSS patients (American-European Consensus Group Criteria, 2002) aged 18-65 years and 71 age-, race-matched control women were enrolled in this case-control study. Clinical data were collected by a standardized protocol. Blood levels of glucose, cholesterol, low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), triglycerides, interleukin-1beta (IL-1beta)/IL-6, B-cell activating factor (BAFF), insulin, and leptin/adiponectin/visfatin/resistin were determined. Patients and controls were comparable regarding body mass index (BMI), smoking, sedentariness, and menopause (p > 0.05). MetS (39.4 vs. 16.9 %, p = 0.005), hypertension (p = 0.004), and dyslipidemia (p = 0.002) were more frequent in patients than controls. IL-1beta, IL-6, BAFF, resistin, and adiponectin levels were higher in patients than controls (p < 0.05). pSS patients with MetS (n = 28) had higher BMI, waist circumference, cholesterol, LDL-C, triglycerides, insulin, leptin and HOMA-IR values, and greater hypertension and diabetes rates than pSS patients without MetS (n = 43) (p < 0.05). Current and/or previous prednisone use (75.0 vs. 62.8 %, p = 0.313), current (3.0 +/- 4.5 vs. 1.6 +/- 3.2 mg/day, p = 0.299), and cumulative prednisone doses (p = 0.495) were similar in both groups. Otherwise, IL-1beta level was higher in MetS patients than in non-MetS patients (p = 0.012), and this finding was confirmed (p = 0.048) by multivariate analysis with adjustments for age, ethnicity, prednisone use, current and cumulative prednisone doses, and duration of use. We identified high MetS frequency and abnormal adipocytokine profile in pSS. The association of MetS with elevated IL 1beta level suggests that inflammation plays an important role in its pathogenesis. PMID- 26370104 TI - Useful Interplay Between Spontaneous ADR Reports and Electronic Healthcare Records in Signal Detection. AB - BACKGROUND AND OBJECTIVE: Spontaneous reporting systems (SRSs) remain the cornerstone of post-marketing drug safety surveillance despite their well-known limitations. Judicious use of other available data sources is essential to enable better detection, strengthening and validation of signals. In this study, we investigated the potential of electronic healthcare records (EHRs) to be used alongside an SRS as an independent system, with the aim of improving signal detection. METHODS: A signal detection strategy, focused on a limited set of adverse events deemed important in pharmacovigilance, was performed retrospectively in two data sources-(1) the Exploring and Understanding Adverse Drug Reactions (EU-ADR) database network and (2) the EudraVigilance database using data between 2000 and 2010. Five events were considered for analysis: (1) acute myocardial infarction (AMI); (2) bullous eruption; (3) hip fracture; (4) acute pancreatitis; and (5) upper gastrointestinal bleeding (UGIB). Potential signals identified in each system were verified using the current published literature. The complementarity of the two systems to detect signals was expressed as the percentage of the unilaterally identified signals out of the total number of confirmed signals. As a proxy for the associated costs, the number of signals that needed to be reviewed to detect one true signal (number needed to detect [NND]) was calculated. The relationship between the background frequency of the events and the capability of each system to detect signals was also investigated. RESULTS: The contribution of each system to signal detection appeared to be correlated with the background incidence of the events, being directly proportional to the incidence in EU-ADR and inversely proportional in EudraVigilance. EudraVigilance was particularly valuable in identifying bullous eruption and acute pancreatitis (71 and 42 % of signals were correctly identified from the total pool of known associations, respectively), while EU-ADR was most useful in identifying hip fractures (60 %). Both systems contributed reasonably well to identification of signals related to UGIB (45 % in EudraVigilance, 40 % in EU-ADR) but only fairly for signals related to AMI (25 % in EU-ADR, 20 % in EudraVigilance). The costs associated with detection of signals were variable across events; however, it was often more costly to detect safety signals in EU ADR than in EudraVigilance (median NNDs: 7 versus 5). CONCLUSION: An EHR-based system may have additional value for signal detection, alongside already established systems, especially in the presence of adverse events with a high background incidence. While the SRS appeared to be more cost effective overall, for some events the costs associated with signal detection in the EHR might be justifiable. PMID- 26370105 TI - Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): A National Analysis of Data from 10-Year Post-marketing Surveillance. AB - INTRODUCTION: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare, severe and potentially fatal cutaneous adverse drug reaction (the mortality rate is up to 10 %) associated with numerous and apparently heterogeneous drugs. The aetiology is unknown. OBJECTIVE: To report Italian cases of DRESS over a 10 year period. METHODS: We searched the National Pharmacovigilance Network (NPN) for the term 'drug reaction with eosinophilia and systemic symptoms' from 1 January 2004 to 1 January 2014, to identify all reports of DRESS. Each case was checked to avoid duplication. RESULTS: In the NPN, we identified 91 serious cases of DRESS: 68 were spontaneous, still-unpublished reports, while 23 additional cases were derived from screening of the scientific literature, performed by marketing authorization holders. Notably, the single common element linking all cases of DRESS was intake of a drug containing an aromatic ring. CONCLUSION: Thanks to the largest national DRESS case series ever reported, we were able to hypothesize, for the first time, that there is an association between use of drugs containing an aromatic ring in their chemical structure and DRESS. This might aid understanding of the aetiology of DRESS and facilitate diagnosis. PMID- 26370107 TI - The complete mitochondrial genome of Epinephelus awoara (Perciformes: Epinephelus) with phylogenetic consideration. AB - The complete mitochondrial genome of the Epinephelus awoara was presented in this study. The mitochondrial genome is 16 798-bp long and consists of 13 protein coding genes, 2 rRNA genes, 22 tRNA genes, and a control region. The gene order and composition of Epinephelus awoara mitochondrial genome was similar to that of most other vertebrates. The nucleotide compositions of the light strand in descending order is 27.35% of A, 16.53% of C, 28.44% of T, and 27.69% of G. With the exception of the NADH dehydrogenase subunit 6 (ND6) and eight tRNA genes, all other mitochondrial genes are encoded on the heavy strand. The phylogenetic analysis by maximum-likelihood (ML) method shows that the Epinephelus awoara was closer to Epinephelus fasciatomaculosus in the phylogenetic relationship. PMID- 26370106 TI - Drug-Induced Hyperglycaemia and Diabetes. AB - Drug-induced hyperglycaemia and diabetes is a global issue. It may be a serious problem, as it increases the risk of microvascular and macrovascular complications, infections, metabolic coma and even death. Drugs may induce hyperglycaemia through a variety of mechanisms, including alterations in insulin secretion and sensitivity, direct cytotoxic effects on pancreatic cells and increases in glucose production. Antihypertensive drugs are not equally implicated in increasing serum glucose levels. Glycaemic adverse events occur more frequently with thiazide diuretics and with certain beta-blocking agents than with calcium-channel blockers and inhibitors of the renin-angiotensin system. Lipid-modifying agents may also induce hyperglycaemia, and the diabetogenic effect seems to differ between the different types and daily doses of statins. Nicotinic acid may also alter glycaemic control. Among the anti infectives, severe life-threatening events have been reported with fluoroquinolones, especially when high doses are used. Protease inhibitors and, to a lesser extent, nucleoside reverse transcriptase inhibitors have been reported to induce alterations in glucose metabolism. Pentamidine-induced hyperglycaemia seems to be related to direct dysfunction in pancreatic cells. Phenytoin and valproic acid may also induce hyperglycaemia. The mechanisms of second-generation antipsychotic-associated hyperglycaemia, diabetes mellitus and ketoacidosis are complex and are mainly due to insulin resistance. Antidepressant agents with high daily doses seem to be more frequently associated with an increased risk of diabetes. Ketoacidosis may occur in patients receiving beta adrenergic stimulants, and theophylline may also induce hyperglycaemia. Steroid diabetes is more frequently associated with high doses of glucocorticoids. Some chemotherapeutic agents carry a higher risk of hyperglycaemia, and calcineurin inhibitor-induced hyperglycaemia is mainly due to a decrease in insulin secretion. Hyperglycaemia has been associated with oral contraceptives containing high doses of oestrogen. Growth hormone therapy and somatostatin analogues may also induce hyperglycaemia. Clinicians should be aware of medications that may alter glycaemia. Efforts should be made to identify and closely monitor patients receiving drugs that are known to induce hyperglycaemia. PMID- 26370108 TI - hTERT promotes the invasion of gastric cancer cells by enhancing FOXO3a ubiquitination and subsequent ITGB1 upregulation. AB - BACKGROUND AND AIMS: Human telomerase reverse transcriptase (hTERT) plays an important role in cancer invasion, but the relevant mechanism is not well known. This study aims to investigate the role and mechanism of hTERT in gastric cancer metastasis. DESIGN: Proteomics analysis, qPCR and western blotting were used to screen for hTERT-regulated candidate molecules in gastric cancer invasion. Chromatin immunoprecipitation (ChIP) qPCR was performed to identify the binding sites of hTERT at the regulatory region of the integrin beta1 (ITGB1) gene. ChIP assays were further applied to elucidate the transcription factors that bound to the regulatory region. The interactions between hTERT and the transcription factors were tested by co-immunoprecipitation (Co-IP) and glutathione S transferase (GST) pull-down experiments. Moreover, the revealed pathway was verified in tumour-bearing nude mice and human gastric cancer tissues. RESULTS: ITGB1 was identified as a downstream gene of hTERT, and there were two hTERT binding regions within this gene. hTERT alleviated the binding of forkhead box O3 (FOXO3a) to FOXO3a binding element (+9972~+9978), but it enhanced the binding of forkhead box M1 (FOXM1) to FOXM1 binding element (-1104~-1109) in ITGB1 gene. Importantly, FOXO3a played a major role in hTERT-induced ITGB1 expression, and the hTERT/murine double minute 2 (MDM2) complex promoted the ubiquitin-mediated degradation of FOXO3a. Moreover, hTERT increased ITGB1 expression in xenograft gastric cancer, and the level of hTERT was positively correlated with that of ITGB1 in human gastric cancer tissues. CONCLUSIONS: The hTERT/MDM2-FOXO3a-ITGB1 pathway markedly contributes to hTERT-promoted gastric cancer invasion, suggesting that this pathway might be a novel target for the prevention and treatment of gastric cancer metastasis. PMID- 26370109 TI - Attendance and diagnostic yield of repeated two-sample faecal immunochemical test screening for colorectal cancer. AB - OBJECTIVE: Limited data exist on attendance and additional yield of 2-sample faecal immunochemical testing (FIT) screening during multiple rounds. We therefore conducted a population-based colorectal cancer screening trial comparing attendance and yield of repeated 1-sample and 2-sample FIT screenings. DESIGN: Two randomly selected groups of average-risk subjects aged 50-74 years were invited for two rounds of either 1-sample (n=5007) or 2-sample (n=3197) FIT (OC-sensor Micro) screening. The test was considered positive if at least one sample was positive (cut-off 50 ng/mL; 10 ug haemoglobin/g). RESULTS: The cumulative attendance rate was similar for repeated 1-sample and 2-sample FIT screenings (1-sample FIT: 68.1%; 2-sample FIT: 67.1%, p=0.368). The positivity rate in the second round was lower for 1-sample FIT (6.2%, 95% CI 5.4% to 7.2%) than for 2-sample FIT (8.4%, 95% CI 7.1% to 9.8%, p=0.007), whereas the detection rate of advanced neoplasia (AN, 1-sample FIT: 1.9%, 95% CI 1.2% to 2.2%; 2-sample FIT: 1.7%, 95% CI 1.2% to 2.5%, p=0.861) and the positive predictive value (1 sample FIT: 32%, 95% CI 24% to 40%; 2-sample FIT: 21%, 95% CI 15% to 29%, p=0.075) did not differ. After two rounds of screening, the cumulative diagnostic yield of AN for 1-sample FIT was 29.3 per 1000 invitees, compared with 34.0 for 2 sample FIT (p=0.241). CONCLUSIONS: Using 2-sample FIT instead of 1-sample FIT does not result in a higher detection rate of AN in the second round of repeated FIT screening. Furthermore, both strategies lead to a similar yield of AN over two rounds. These findings imply that 1-sample FIT screening is preferred over 2 sample FIT screening. PMID- 26370111 TI - Pervasive Effects of Wildfire on Foliar Endophyte Communities in Montane Forest Trees. AB - Plants in all terrestrial ecosystems form symbioses with endophytic fungi that inhabit their healthy tissues. How these foliar endophytes respond to wildfires has not been studied previously, but is important given the increasing frequency and intensity of severe wildfires in many ecosystems, and because endophytes can influence plant growth and responses to stress. The goal of this study was to examine effects of severe wildfires on endophyte communities in forest trees, with a focus on traditionally fire-dominated, montane ecosystems in the southwestern USA. We evaluated the abundance, diversity, and composition of endophytes in foliage of Juniperus deppeana (Cupressaceae) and Quercus spp. (Fagaceae) collected contemporaneously from areas affected by recent wildfire and paired areas not affected by recent fire. Study sites spanned four mountain ranges in central and southern Arizona. Our results revealed significant effects of fires on endophyte communities, including decreases in isolation frequency, increases in diversity, and shifts in community structure and taxonomic composition among endophytes of trees affected by recent fires. Responses to fire were similar in endophytes of each host in these fire-dominated ecosystems and reflect regional fire-return intervals, with endophytes after fire representing subsets of the regional mycoflora. Together, these findings contribute to an emerging perspective on the responses of diverse communities to severe fire, and highlight the importance of considering fire history when estimating endophyte diversity and community structure for focal biomes. PMID- 26370112 TI - Soil Parameters Drive the Structure, Diversity and Metabolic Potentials of the Bacterial Communities Across Temperate Beech Forest Soil Sequences. AB - Soil and climatic conditions as well as land cover and land management have been shown to strongly impact the structure and diversity of the soil bacterial communities. Here, we addressed under a same land cover the potential effect of the edaphic parameters on the soil bacterial communities, excluding potential confounding factors as climate. To do this, we characterized two natural soil sequences occurring in the Montiers experimental site. Spatially distant soil samples were collected below Fagus sylvatica tree stands to assess the effect of soil sequences on the edaphic parameters, as well as the structure and diversity of the bacterial communities. Soil analyses revealed that the two soil sequences were characterized by higher pH and calcium and magnesium contents in the lower plots. Metabolic assays based on Biolog Ecoplates highlighted higher intensity and richness in usable carbon substrates in the lower plots than in the middle and upper plots, although no significant differences occurred in the abundance of bacterial and fungal communities along the soil sequences as assessed using quantitative PCR. Pyrosequencing analysis of 16S ribosomal RNA (rRNA) gene amplicons revealed that Proteobacteria, Acidobacteria and Bacteroidetes were the most abundantly represented phyla. Acidobacteria, Proteobacteria and Chlamydiae were significantly enriched in the most acidic and nutrient-poor soils compared to the Bacteroidetes, which were significantly enriched in the soils presenting the higher pH and nutrient contents. Interestingly, aluminium, nitrogen, calcium, nutrient availability and pH appeared to be the best predictors of the bacterial community structures along the soil sequences. PMID- 26370110 TI - Minimally Invasive Sampling Method Identifies Differences in Taxonomic Richness of Nasal Microbiomes in Young Infants Associated with Mode of Delivery. AB - To date, there is a limited understanding of the role of the airway microbiome in the early life development of respiratory diseases such as asthma, partly due to a lack of simple and minimally invasive sample collection methods. In order to characterize the baseline microbiome of the upper respiratory tract (URT) in infants, a comparatively non-invasive method for sampling the URT microbiome suitable for use in infants was developed. Microbiome samples were collected by placing filter paper in the nostrils of 33 healthy, term infants enrolled as part of the Infant Susceptibility to Pulmonary Infections and Asthma Following RSV Exposure (INSPIRE) study. After bacterial genomic DNA was extracted from the filters, amplicons were generated with universal primers targeting the V1-V3 region of the 16S rRNA gene. This method was capable of capturing a wide variety of taxa expected to inhabit the nasal cavity. Analyses stratifying subjects by demographic and environmental factors previously observed or predicted to influence microbial communities were performed. Microbial community richness was found to be higher in infants who had been delivered via Cesarean section and in those who had been formula-fed; an association was observed between diet and delivery, which confounds this analysis. We have established a baseline URT microbiome using a non-invasive filter paper nasal sampling for this population, and future studies will be performed in this large observational cohort of infants to investigate the relationship between viral infections, the URT microbiota, and the development of childhood wheezing illnesses. PMID- 26370113 TI - The simple advantage in perceptual and categorical generalization. AB - Recent research in relational learning has suggested that simple training instances may lead to better generalization than complex training instances. We examined the perceptual-encoding mechanisms that might undergird this "simple advantage" by testing category and perceptual learning in adults with simplified and traditional (more complex) Chinese scripts. In Experiment 1, participants learned Chinese characters and their English translations, performed a memorization test, and generalized their learning to the corresponding characters written in the other script. In Experiment 2, we removed the training phase and modified the tests to examine transfer based purely on the perceptual similarities between simplified and traditional characters. We found the simple advantage in both experiments. Training with simplified characters produced better generalization than training with traditional characters when generalization relied on either recognition memory or pure perceptual similarities. On the basis of the results of these two experiments, we propose a simple process model to explain the perceptual mechanism that might drive this simple advantage, and in Experiment 3 we tested novel predictions of this model by examining the effect of exposure duration on the simple advantage. We found support for our model that the simple advantage is driven primarily by differences in the perceptual encoding of the information available from simple and complex instances. These findings advance our understanding of how the perceptual features of a learning opportunity interact with domain-general mechanisms to prepare learners for transfer. PMID- 26370114 TI - Who is more vulnerable to death from extremely cold temperatures? A case-only approach in Hong Kong with a temperate climate. AB - The short-term effects of ambient cold temperature on mortality have been well documented in the literature worldwide. However, less is known about which subpopulations are more vulnerable to death related to extreme cold. We aimed to examine the personal characteristics and underlying causes of death that modified the association between extreme cold and mortality in a case-only approach. Individual information of 197,680 deaths of natural causes, daily temperature, and air pollution concentrations in cool season (November-April) during 2002-2011 in Hong Kong were collected. Extreme cold was defined as those days with preceding week with a daily maximum temperature at or less than the 1st percentile of its distribution. Logistic regression models were used to estimate the effects of modification, further controlling for age, seasonal pattern, and air pollution. Sensitivity analyses were conducted by using the 5th percentile as cutoff point to define the extreme cold. Subjects with age of 85 and older were more vulnerable to extreme cold, with an odds ratio (OR) of 1.33 (95 % confidence interval (CI), 1.22-1.45). The greater risk of extreme cold-related mortality was observed for total cardiorespiratory diseases and several specific causes including hypertensive diseases, stroke, congestive heart failure, chronic obstructive pulmonary disease (COPD), and pneumonia. Hypertensive diseases exhibited the greatest vulnerability to extreme cold exposure, with an OR of 1.37 (95 % CI, 1.13-1.65). Sensitivity analyses showed the robustness of these effect modifications. This evidence on which subpopulations are vulnerable to the adverse effects of extreme cold is important to inform public health measures to minimize those effects. PMID- 26370115 TI - Quality changes of cuttlefish stored under various atmosphere modifications and vacuum packaging. AB - BACKGROUND: Seafood preservation and its shelf life prolongation are two of the main issues in the seafood industry. As a result, and in view of market globalization, research has been triggered in this direction by applying several techniques such as modified atmosphere packaging (MAP), vacuum packaging (VP) and active packaging (AP). However, seafood such as octopus, cuttlefish and others have not been thoroughly investigated up to now. The aim of this research was to determine the optimal conditions of modified atmosphere under which cuttlefish storage time and consequently shelf life time could be prolonged without endangering consumer safety. RESULTS: It was found that cuttlefish shelf life reached 2, 2, 4, 8 and 8 days for control, VP, MAP 1, MAP 2 and MAP 3 (20% CO2 80% N2 , 50% CO2 -50% N2 and 70% CO2 -30% N2 for MAP 1, 2 and 3, respectively) samples, respectively, judging by their sensorial attributes. Elevated CO2 levels had a strong microbiostatic effect, whereas storage under vacuum did not offer significant advantages. All physicochemical attributes of MAP-treated samples were better preserved compared to control. CONCLUSION: Application of high CO2 atmospheres such as MAP 2 and MAP 3 proved to be an effective strategy toward preserving the characteristics and prolonging the shelf life of fresh cuttlefish and thereby improving its potential in the market. (c) 2015 Society of Chemical Industry. PMID- 26370116 TI - Integrated approach to the understanding of the degradation of an urban river: local perceptions, environmental parameters and geoprocessing. AB - BACKGROUND: The use of interdisciplinary approaches such as the proposed report provides a broad understanding of the relationship between people and the environment, revealing reliable aspects not previously considered in the study of this relationship. This study compiled evidence on the environmental degradation of an urbanized river over the past few decades, providing a diagnosis of the consequences of this process for the river, its ichthyofauna, and the local human population. METHODS: The study was focused on the Beira Rio community on the Capibaribe River in the municipality of Sao Lourenco da Mata, Pernambuco, Brazil. Data were collected using geoprocessing and ethnobiological approaches, as well as environmental parameters. This research was conducted with the most experienced long-term residents in the local community, through interviews and participatory methodologies to recovering information about the river environment, its ichthyofauna and its environmental services for the last decades. RESULTS: According to the GIS analysis, the study area was subject to an accelerated process of urbanization, with the total urban area increasing from 73 565, 98 m(2) in 1974 to 383 363, 6 m(2) in 2005. The informants perceived the urban growth, especially in the late twentieth century, being this period recognized as the phase of greatest negative changes in the river environment. The perceived decline of fish stocks was indicated by the community as one of the effects of river degradation. According to the interviews, the deterioration of the river affected the ecosystem services and the relationship of the adjacent human community with this ecosystem. The environmental data indicated that the river is suffering eutrophization and has fecal coliform concentrations 160 times higher than the maximum level permitted by Brazilian legislation. CONCLUSIONS: The interdisciplinary approach used in this research allowed the understanding of the degradation process of an urban river and some negative effects through the integration of environmental data, GIS and the local knowledge, revealing the complementarity of obtained data and the effectiveness of implementation of this approach. PMID- 26370117 TI - Molecular profiles of cancer stem-like cell populations in aggressive thyroid cancers. AB - A substantial proportion of patients with advanced thyroid carcinoma fail to respond to or at some point become refractory to conventional therapies. This resistance and the phenomena of thyroid cancer progression and metastasis themselves are thought to be related to tumor-cell sub-populations with stem-like properties. We isolated thyrospheres from four advanced thyroid carcinomas that were resistant to radioiodine therapy and analyzed their molecular profiles. ALDH activity and proteomic profile of main stem cell markers were used to assess stem cell properties. The TaqMan Low Density Array approach was used to evaluate the expression of several genes involved in the EMT process. The phosphorylation status of tyrosine kinase receptors (RTKs) was analyzed to identify potential markers for targeted therapies. We then investigated the effects of the EMT inhibitor crizotinib on both cell proliferation and phosphorylation status of RTK targets. The cancer stem-like properties of a subset of cells from primary cultures of each tumor were demonstrated. A wide variability among thyrospheres arising from the four thyroid cancers in terms of ALDH activity, stem cell marker expression, and phosphoproteome profiling was present. Dysregulated expression of genes involved in the EMT was observed in all four thyrosphere lines. Treatment with crizotinib was ineffective in cancer stem-like cells, suggesting the presence of a mechanism of resistance in thyrospheres. Collectively, our data indicate that thyroid cancer stem-like populations vary markedly from tumor to tumor and require detailed molecular and biological characterization if they are to be used as the basis of "personalized" treatment of aggressive disease. PMID- 26370118 TI - A multifunctional diet improves cardiometabolic-related biomarkers independently of weight changes: an 8-week randomized controlled intervention in healthy overweight and obese subjects. AB - PURPOSE: A multifunctional diet (MFD) was previously shown to reduce blood lipids, CRP and blood pressure in a 4-week intervention under weight-maintenance conditions. Here, MFD effects were evaluated in an 8-week intervention with no restriction for weight changes. METHODS: Healthy subjects consumed MFD (23 subjects) or a control diet (CD) devoid of the functional components (24 subjects) in a "free-living" randomized controlled experiment. MFD included several functional concepts: low-glycemic-impact meals, antioxidant-rich foods, oily fish, viscous dietary fibers, soybean and whole barley kernel products, almonds and plant stanols. Measured outcomes were fasting blood values of lipids, glucose, insulin, GGT, CRP, HbA1c, PAI-1, GLP-1, GLP-2, body weight, blood pressure and breath hydrogen. RESULTS: At baseline, participants were 51-72 years old, with BMI between 25 and 34 and fasting glycemia <= 6.1 mmol/L. Consumption of both diets resulted in similar weight loss after 8 weeks (-4 %; P < 0.001). Compared to baseline, consumption of MFD reduced total serum cholesterol (-26 %; P < 0.0001), LDL cholesterol (-35 %; P < 0.0001), triglycerides (-16 %; P < 0.05), LDL/HDL (-27 %; P < 0.0001) and ApoB/ApoA1 (-15 %; P < 0.0001). There were important net differences between diets, which remained significant after adjustment for body weight. Reduced systolic blood pressure, circulating GGT, HbA1c and insulin concentrations were observed with both MFD and CD with no difference between diets. The Reynolds cardiovascular risk score was decreased by 36 % (P < 0.0001) with MFD. MFD increased breath hydrogen levels (120 %; P < 0.05). CONCLUSIONS: Consumption of MFD decreased blood lipids and improved several other aspects of the cardiometabolic risk profile. This effect was not dependent on weight loss. PMID- 26370119 TI - Applicability of HIN-1, MGMT and RASSF1A promoter methylation as biomarkers for detecting field cancerization in breast cancer. AB - INTRODUCTION: It has been shown in some articles that genetic and epigenetic abnormalities cannot only be found in tumor tissues but also in adjacent regions that appear histologically normal. This phenomenon is metaphorically called field cancerization or field defect. Field cancerization is regarded as clinically significant because it is assumed to be an important factor in local recurrence of cancer. As the field showing these molecular abnormalities may not be removed completely by surgery, these changes might lead to neoplasms and subsequent transformation to a tumor. We aimed to investigate the applicability of the methylation status of six tumor suppressor genes as biomarkers for detecting field cancerization in breast cancer. METHODS: The promoter methylation status of CCND2, DAPK1, GSTP1, HIN-1, MGMT and RASSF1A was determined by methylation sensitive high-resolution melting (MS-HRM) analysis. MS-HRM methods for CCND2, MGMT and RASSF1A were developed in-house, primer sequences for DAPK1, GSTP1 and HIN-1 have already been published. Biopsy samples were taken from tumor, tumor adjacent and tumor-distant tissue from 17 breast cancer patients. Normal breast tissues of four healthy women served as controls. RESULTS: All MS-HRM methods proved to be very sensitive. LODs were in the range from 0.1 to 1.5 %, LOQs ranged from 0.3 to 5.3 %. A total of 94 %, 82 % and 65 % of the tumors showed methylation of RASSF1A, HIN-1 and MGMT promoters, respectively. The methylation status of these promoters was significantly lower in tumor-distant tissues than in tumor tissues. Tumor-adjacent tissues showed higher methylation status of RASSF1A, HIN-1 and MGMT promoters than tumor-distant tissues, indicating field cancerization. The methylation status of the HIN-1 promoter in tumor-adjacent tissues was found to correlate strongly with that in the corresponding tumors (r = 0.785, p < 0.001), but not with that in the corresponding tumor-distant tissues (r = 0.312, p = 0.239). CONCLUSIONS: Among the gene promoters investigated, the methylation status of the HIN-1 promoter can be considered the best suitable biomarker for detecting field cancerization. Further investigation is needed to test whether it can be used for defining surgical margins in order to prevent future recurrence of breast cancer. PMID- 26370120 TI - Brief screening items to identify spanish-speaking adults with limited health literacy and numeracy skills. AB - BACKGROUND: Limited health literacy (HL) and numeracy have been shown to be associated with a wide array of poor health-related outcomes, knowledge, and behaviors. The purpose of this study was to evaluate the clinical utility of brief HL and numeracy screening items in identifying Spanish-speaking adults' HL and numeracy skills. METHODS: We studied convenience samples of native Spanish speaking adults in Columbus, Ohio. A trained research assistant administered sociodemographic items, HL and numeracy screening items, Short Assessment of Health Literacy (SAHL), and Newest Vital Sign (NVS) to participants in Spanish. RESULTS: Participants (n = 151) averaged 36.8 +/- 11.0 years of age and 54.7% were female. Average SAHL score was 15.7 +/- 2.8 (range = 4 to 18), while the average NVS score was 1.7 +/- 1.5 (range = 0 to 6). "How confident are you filling out medical forms by yourself?" performed best in detecting limited NVS scores (AUROC = 0.66; 95% confidence interval [CI] = 0.57-0.75), limited/marginal NVS scores (AUROC = 0.75; 95% CI = 0.65-0.84), and inadequate SAHL scores (AUROC = 0.69; 95% CI = 0.58-0.79). CONCLUSION: A single HL screening item is useful for quickly estimating HL and numeracy skills in native Spanish-speaking adults. PMID- 26370121 TI - Incidence and survival of retinoblastoma in Taiwan: a nationwide population-based study 1998-2011. AB - OBJECTIVE: To study the epidemiology of retinoblastoma in Taiwan from 1998 to 2011. DESIGN: This was a retrospective population-based cohort study using the Taiwan National Health Insurance Research Database. RESULTS: The present study included 154 patients (92 males, 62 females) with retinoblastoma and the documented overall retinoblastoma incidence was 1 in 17 373 live births without a notable trend over the study period. The incidence per million live births examined by gender was 65.8 for males and 48.5 for females. The age-specific sex ratio increased from 1.4 at age younger than 1 year to 3.0 above age 4 years. Enucleation was performed in 109 (70.8%) children with retinoblastoma, and it was more prevalent in males than in females (77.2% vs 61.3%, p=0.0335). Multivariate Cox regression analyses with adjustment for diagnostic age, sex, and birth year elucidated that enucleation was a significant factor associated with survival (OR 0.27, 95% CI 0.10 to 0.61). CONCLUSIONS: The incidence of retinoblastoma in Taiwan exhibited no marked trend over time. There were more cases of males than females and the male-to-female rate ratio increased with age. Survival outcome was significantly associated with the intervention of enucleation. PMID- 26370123 TI - Severe symptomatic babesiosis co-infection with Lyme disease. PMID- 26370122 TI - Putative synaptic genes defined from a Drosophila whole body developmental transcriptome by a machine learning approach. AB - BACKGROUND: Assembly and function of neuronal synapses require the coordinated expression of a yet undetermined set of genes. Although roughly a thousand genes are expected to be important for this function in Drosophila melanogaster, just a few hundreds of them are known so far. RESULTS: In this work we trained three learning algorithms to predict a "synaptic function" for genes of Drosophila using data from a whole-body developmental transcriptome published by others. Using statistical and biological criteria to analyze and combine the predictions, we obtained a gene catalogue that is highly enriched in genes of relevance for Drosophila synapse assembly and function but still not recognized as such. CONCLUSIONS: The utility of our approach is that it reduces the number of genes to be tested through hypothesis-driven experimentation. PMID- 26370124 TI - Cutaneous melioidosis. PMID- 26370125 TI - Tracheobronchopathia osteochondroplastica: an unusual cause of chronic cough. PMID- 26370126 TI - Is medicine still a profession? AB - The Oxford English Dictionary (OED) defines a profession as 'a vocation or calling especially one that involves some branch of advanced learning or science (the Medical Profession)'. A vocation in this sense means work in a field that requires dedication. Other distinguishing features include work that deals with vital issues such as matters of life-or-death for medicine, freedom-or-internment for the law, war-or-peace for politicians, defence-or-attack for the military, etc. Such professionals have a certain amount of autonomy to decide what needs doing. They are never on holiday; doctors are expected to treat patients in an emergency whatever the time or place; politicians interrupt their holidays to debate matters of war or peace. They consider the value of their work to be above disputes about salary or pensions and do not go on strike for such issues. In return, they earn a certain amount of respect and trust from the public they serve. PMID- 26370127 TI - An uncommon cause of melena--left gastric artery pseudoaneurysm. PMID- 26370128 TI - Erratum to: A novel placental like alkaline phosphatase promoter driven transcriptional silencing combined with single chain variable fragment antibody based virosomal delivery for neoplastic cell targeting. PMID- 26370130 TI - Why does mutation of Gln61 in Ras by the nitro analog NGln maintain activity of Ras-GAP in hydrolysis of guanosine triphosphate? AB - Interpretation of the experiments showing that the Ras-GAP protein complex maintains activity in guanosine triphosphate (GTP) hydrolysis upon replacement of Glu61 in Ras with its unnatural nitro analog, NGln, is an important issue for understanding details of chemical transformations at the enzyme active site. By using molecular modeling we demonstrate that both glutamine and its nitro analog in the aci-nitro form participate in the reaction of GTP hydrolysis at the stages of proton transfer and formation of inorganic phosphate. The computed structures and the energy profiles for the complete pathway from the enzyme-substrate to enzyme-product complexes for the wild-type and mutated Ras suggest that the reaction mechanism is not affected by this mutation. PMID- 26370129 TI - Construction of polyomavirus-derived pseudotype virus-like particles displaying a functionally active neutralizing antibody against hepatitis B virus surface antigen. AB - BACKGROUND: Virus-like particles (VLPs) can be efficiently produced by heterologous expression of viral structural proteins in yeast. Due to their repetitive structure, VLPs are extensively used for protein engineering and generation of chimeric VLPs with inserted foreign epitopes. Hamster polyomavirus VP1 represents a promising epitope carrier. However, insertion of large sized protein sequences may interfere with its self-assembly competence. The co expression of polyomavirus capsid protein VP1 with minor capsid protein VP2 or its fusion protein may result in pseudotype VLPs where an intact VP1 protein mediates VLP formation. In the current study, the capacity of VP1 protein to self assemble to VLPs and interact with the modified VP2 protein has been exploited to generate pseudotype VLPs displaying large-sized antibody molecules. RESULTS: Polyomavirus-derived pseudotype VLPs harbouring a surface-exposed functionally active neutralizing antibody specific to hepatitis B virus (HBV) surface antigen (HBsAg) have been generated. The pseudotype VLPs consisting of an intact hamster polyomavirus (HaPyV) major capsid protein VP1 and minor capsid protein VP2 fused with the anti-HBsAg molecule were efficiently produced in yeast Saccharomyces cerevisiae and purified by density-gradient centrifugation. Formation of VLPs was confirmed by electron microscopy. Two types of pseudotype VLPs were generated harbouring either the single-chain fragment variable (scFv) or Fc-engineered scFv on the VLP surface. The antigen-binding activity of the purified pseudotype VLPs was evaluated by ELISA and virus-neutralization assay on HBV-susceptible primary hepatocytes from Tupaia belangeri. Both types of the pseudotype VLPs were functionally active and showed a potent HBV-neutralizing activity comparable to that of the parental monoclonal antibody. The VP2-fused scFv molecules were incorporated into the VLPs with higher efficiency as compared to the VP2-fused Fc scFv. However, the pseudotype VLPs with displayed VP2-fused Fc-scFv molecule showed higher antigen-binding activity and HBV-neutralizing capacity that might be explained by a better accessibility of the Fc-engineered scFv of the VLP surface. CONCLUSIONS: Polyomavirus-derived pseudotype VLPs harbouring multiple functionally active antibody molecules with virus-neutralizing capability may represent a novel platform for developing therapeutic tools with a potential application for post-exposure or therapeutic treatment of viral infections. PMID- 26370131 TI - Vertical-Injection AlGaInP LEDs with n-AlGaInP Nanopillars Fabricated by Self Assembled ITO-Based Nanodots. AB - The light output power of AlGaInP-based vertical-injection light-emitting diodes (VI-LEDs) can be enhanced significantly using n-AlGaInP nanopillars. n-AlGaInP nanopillars, ~200 nm in diameter, were produced using SiO2 nanopillars as an etching mask, which were fabricated from self-assembled tin-doped indium oxide (ITO)-based nanodots formed by the wet etching of as-deposited ITO films. The AlGaInP-based VI-LEDs with the n-AlGaInP nanopillars provided 25 % light output power enhancement compared to VI-LEDs with a surface-roughened n-AlGaInP because of the reduced total internal reflection by the nanopillars at the n-AlGaInP/air interface with a large refractive index difference of 1.9. PMID- 26370132 TI - A Study of the Preparation and Properties of Antioxidative Copper Inks with High Electrical Conductivity. AB - Conductive ink using copper nanoparticles has attracted much attention in the printed electronics industry because of its low cost and high electrical conductivity. However, the problem of easy oxidation under heat and humidity conditions for copper material limits the wide applications. In this study, antioxidative copper inks were prepared by dispersing the nanoparticles in the solution, and then conductive copper films can be obtained after calcining the copper ink at 250 degrees C in nitrogen atmosphere for 30 min. A low sheet resistance of 47.6 mOmega/? for the copper film was measured by using the four point probe method. Importantly, we experimentally demonstrate that the electrical conductivity of copper films can be improved by increasing the calcination temperature. In addition, these highly conductive copper films can be placed in an atmospheric environment for more than 6 months without the oxidation phenomenon, which was verified by energy-dispersive X-ray spectroscopy (EDS). These observations strongly show that our conductive copper ink features high antioxidant properties and long-term stability and has a great potential for many printed electronics applications, such as flexible display systems, sensors, photovoltaic cells, and radio frequency identification. PMID- 26370133 TI - A case of membranoproliferative glomerulonephritis associated with curved fibril deposition. AB - BACKGROUND: It is sometimes challenging to diagnose unsusual cases of fibrillary glomerulonephritis (FGN) and immunotactoid glomerulopathy (ITG), the rare causes of nephrotic syndrome. CASE PRESENTATION: A 75-year-old Japanese woman presented with nephrotic syndrome, microhematuria and renal insufficiency. Renal biopsy revealed membranoproliferative glomerulonephritis (MPGN) with IgM and weak C3 deposition. Congo red stain was negative. Electron microscopy demonstrated massive fibrils in the subendothelium, mesangium and subepithelium. The fibrils were partially parallel, partially curved and 17 nm in diameter. Cryoglobulin, hepatitis B virus (HBV) antigen, hepatitis C virus (HCV) antibody or antinuclear antibody were negative. CONCLUSION: We report a case of MPGN associated with peculiar non-amyloid fibril deposition corresponding to neither FGN nor ITG. PMID- 26370134 TI - Proteomic Analysis on Cercariae and Schistosomula in Reference to Potential Proteases Involved in Host Invasion of Schistosoma japonicum Larvae. AB - Schistosomiasis is a parasitic zoonosis posing great threat to human health. The infection is acquired by larval cercariae penetrating host skin and transforming into juveniles, schistosomula. Proteolytic enzymes secreted from the cercarial acetabular glands are known to aid to the skin penetration, but molecular mechanisms remain largely unclear. To profile the protein composition and identify potential invasive proteases, we developed a new method for simulating cercarial transformation and collecting schistosomula, and for the first time, we compared the proteomes of Schistosoma japonicum cercariae and schistosomula by using in-gel shotgun proteomic analysis. Totally, 1972 proteins were identified in association with ten main biological processes based on Gene Ontology analysis; 46 proteases were detected in cercariae, and among them, 25 proteases disappeared after penetrated. Notably, leishmanolysins and serine and cysteine proteases were found abundant but differentially expressed. Recombinant serine protease SjCE2b and cysteine protease SjCB2 were produced and used for validation of native proteins. Immunofluorescence and Western blotting assays detected SjCE2b and SjCB2 in cercariae but not in schistosomula, suggesting the two enzymes might be consumed upon skin migration. Our data comprehensively chart the proteomic changes during cercarial invasion, revealing the potential proteases involved, providing a platform for the development of molecular anti-infection strategy. PMID- 26370135 TI - A preliminary validation of the Brief COPE instrument for assessing coping strategies among people living with HIV in China. AB - BACKGROUND: The Brief COPE instrument has been utilized to conduct research on various populations, including people living with HIV (PLWH). However, the questionnaire constructs when applied to PLWH have not been subjected to thorough factor validation. METHODS: A total of 258 PLWH were recruited from two provinces of China. They answered questions involving the scales of three instruments: the Brief COPE, the Perceived Social Support Scale, and the Perceived Discrimination Scale for PLWH. Confirmatory factor analysis (CFA) and exploratory factor analysis (EFA) were conducted. RESULTS: The CFA found a poor goodness of fit to the data. The subsequent EFA identified six preliminary factors, forming subscales with Cronbach's alphas, which ranged from 0.61 to 0.80. Significant correlation coefficients between the subscales and measures of perceived social support and perceived discrimination were reported, giving preliminary support to the validity of the new empirical factor structure. CONCLUSION: This study showed that the original factor structure of the Brief COPE instrument, when applied to PLWH in China, did not fit the data. Thus, the Brief COPE should be applied to various populations and cultures with caution. The new factor structure established by the EFA is only preliminary and requires further validation. PMID- 26370136 TI - Efficacy and safety of aclidinium bromide in patients with COPD: A phase 3 randomized clinical trial in a Korean population. AB - BACKGROUND AND OBJECTIVE: Aclidinium bromide ('aclidinium') is a novel, inhaled long-acting muscarinic antagonist. Therapeutic effects of aclidinium on chronic obstructive pulmonary disease (COPD) have been demonstrated in Caucasian populations in several clinical trials. This was a randomized, double-blind, multi-centre phase-3 clinical trial to evaluate the efficacy and safety of aclidinium in a Korean population. METHODS: A total of 263 Korean patients with moderate-to-severe COPD were randomized to receive aclidinium (400 MUg, bd) (Genuai) or placebo via a dry-powder inhaler. The primary end point was change in trough forced expiratory volume in one second (FEV1 ) at 12 weeks. Other lung function measurements, COPD exacerbation, health status (St George's Respiratory Questionnaire (SGRQ), dyspnoea (Transition Dyspnea Index (TDI) and safety were assessed throughout the study period. RESULTS: A significant improvement in trough FEV1 from baseline was shown with aclidinium compared with the placebo (0.126 L, P < 0.0001). Significant improvements were also demonstrated in peak FEV1 (0.190 L, P < 0.0001), SGRQ and TDI. Furthermore, aclidinium significantly reduced the prevalence of exacerbations (aclidinium, 5.4%; placebo, 15.6%, P < 0.05), and the duration of exacerbations was shorter compared with placebo (rate ratio: 0.27; P < 0.05). Aclidinium (400 MUg) was well tolerated and the prevalence of adverse events was comparable with the placebo. CONCLUSIONS: Inhaled aclidinium (400 MUg) was shown to be safe and efficacious in Korean patients with moderate-to-severe COPD. CLINICAL TRIAL REGISTRATION: NCT01636401 at Clinicaltrials.gov. PMID- 26370137 TI - Clinical characteristics and antimicrobial susceptibility of Bacillus cereus blood stream infections. AB - BACKGROUND: Bacillus cereus is one of the pathogens causing nosocomial bloodstream infections (BSIs). However, few reports have documented the antimicrobial susceptibility and clinical characteristics of Bacillus cereus BSI and the importance of empirical therapy. The aim of this study was to investigate the clinical characteristics and antimicrobial susceptibility of B. cereus isolates from patients with BSI and to analyze the impact of appropriate empirical therapy on the outcome of patients with B. cereus BSI. METHODS: All adult cases of bacteremia between April 2003 and March 2012 in a teaching hospital in Tokyo, Japan were reviewed retrospectively. Clinical data were collected from the patients' medical records and charts. Antimicrobial susceptibility testing was performed by broth microdilution method. The patients with B. cereus BSI were divided into an appropriate empirical therapy group and an inappropriate empirical therapy group. The primary outcome was all-cause mortality at 4 weeks after the start of BSI. The secondary outcome was early defervescence within 2 days after starting empirical therapy. RESULTS: There were 29 B. cereus bloodstream infection cases. No vancomycin, gentamicin, and imipenem resistant isolates were found. However, 65.5 % were resistant to clindamycin and 10.3 % were resistant to levofloxacin. The main etiology was venous catheter related (69 %). All-cause mortality at 4 weeks was not significantly different between the appropriate empirical therapy group (9 cases) and the inappropriate group (20 cases) in this study. However, early defervescence within 2 days after starting empirical therapy was significantly different (p = 0.032). CONCLUSIONS: The BSI of B. cereus is mostly caused by venous catheter-related infections. Appropriate empirical therapy is important to achieve early clinical resolution in B. cereus BSI. Vancomycin is one of the appropriate selections of empirical therapy for B. cereus BSI. PMID- 26370139 TI - How healthy is a gluten-free diet? PMID- 26370138 TI - Activation of acid-sensing ion channels by localized proton transient reveals their role in proton signaling. AB - Extracellular transients of pH alterations likely mediate signal transduction in the nervous system. Neuronal acid-sensing ion channels (ASICs) act as sensors for extracellular protons, but the mechanism underlying ASIC activation remains largely unknown. Here, we show that, following activation of a light-activated proton pump, Archaerhodopsin-3 (Arch), proton transients induced ASIC currents in both neurons and HEK293T cells co-expressing ASIC1a channels. Using chimera proteins that bridge Arch and ASIC1a by a glycine/serine linker, we found that successful coupling occurred within 15 nm distance. Furthermore, two-cell sniffer patch recording revealed that regulated release of protons through either Arch or voltage-gated proton channel Hv1 activated neighbouring cells expressing ASIC1a channels. Finally, computational modelling predicted the peak proton concentration at the intercellular interface to be at pH 6.7, which is acidic enough to activate ASICs in vivo. Our results highlight the pathophysiological role of proton signalling in the nervous system. PMID- 26370140 TI - Assessment of the Clinical Utility of Glypican 3 as a Serum Marker for the Diagnosis of Hepatocellular Carcinoma. AB - Glypican-3 has been reported to be one of the most promising serum markers for hepatocellular carcinoma. This study aimed to assess the clinical utility of serum glypican 3 for the diagnosis of hepatocellular carcinoma. We recruited consecutive patients on a large scale, 283 with hepatocellular carcinoma, 445 with chronic hepatic diseases, and 162 normal controls, to assess the diagnostic accuracy of serum glypican 3 for hepatocellular carcinoma by enzyme-linked immunosorbent assay. In addition, we further analyzed the relationship between the serum levels of alpha-fetoprotein and glypican-3 in patients with hepatocellular carcinoma. The results indicated that serum glypican 3 was elevated in patients with hepatocellular carcinoma (0 ng/mL, range = 0-14.0 ng/mL, P = .033) and liver cirrhosis (0 ng/mL, range = 0-12.5 ng/mL, P = .001) compared to the levels in normal control (0 ng/mL, range = 0-4.3 ng/mL), but there was no difference between hepatocellular carcinoma and liver cirrhosis (P = .097). The area under the curve of the receiver-operating characteristics curve for hepatocellular carcinoma versus all controls was 0.519, with a sensitivity of 39.9%, a specificity of 60.6%, and an optimal cutoff value of 0.002 ng/mL. The positive and negative predictive values were 32.0% and 68.3%, respectively. No significant correlation in serum levels was observed between glypican 3 and alpha fetoprotein (P > .05). The diagnostic sensitivity for hepatocellular carcinoma increased to 72.8% (206 of the 283) when glypican 3 was combined with alpha fetoprotein. Glypican 3 was not a promising serum maker for the diagnosis of hepatocellular carcinoma alone, but it could be complementary to alpha fetoprotein and elevate the sensitivity of hepatocellular carcinoma diagnosis. PMID- 26370141 TI - A structural dissection of large protein-protein crystal packing contacts. AB - With the rapid increase in crystal structures of protein-protein complexes deposited in the Protein Data Bank (PDB), more and more crystal contacts have been shown to have similar or even larger interface areas than biological interfaces. However, little attention has been paid to these large crystal packing contacts and their structural principles remain unknown. To address this issue, we used a comparative feature analysis to analyze the geometric and physicochemical properties of large crystal packing contacts by comparing two types of specific protein-protein interactions (PPIs), weak transient complexes and permanent homodimers. Our results show that although large crystal packing contacts have a similar interface area and contact size as permanent homodimers, they tend to be more planar, loosely packed and less hydrophobic than permanent homodimers and cannot form a central core region that is fully buried during interaction. However, the properties of large crystal packing contacts, except for the interface area and contact size, more closely resemble those of weak transient complexes. The large overlap between biological and large crystal packing contacts indicates that interface properties are not efficient indicators for classification of biological interfaces from large crystal packing contacts and finding other specific features urgently needed. PMID- 26370142 TI - Seasonality of Plasmodium falciparum transmission: a systematic review. AB - BACKGROUND: Although Plasmodium falciparum transmission frequently exhibits seasonal patterns, the drivers of malaria seasonality are often unclear. Given the massive variation in the landscape upon which transmission acts, intra-annual fluctuations are likely influenced by different factors in different settings. Further, the presence of potentially substantial inter-annual variation can mask seasonal patterns; it may be that a location has "strongly seasonal" transmission and yet no single season ever matches the mean, or synoptic, curve. Accurate accounting of seasonality can inform efficient malaria control and treatment strategies. In spite of the demonstrable importance of accurately capturing the seasonality of malaria, data required to describe these patterns is not universally accessible and as such localized and regional efforts at quantifying malaria seasonality are disjointed and not easily generalized. METHODS: The purpose of this review was to audit the literature on seasonality of P. falciparum and quantitatively summarize the collective findings. Six search terms were selected to systematically compile a list of papers relevant to the seasonality of P. falciparum transmission, and a questionnaire was developed to catalogue the manuscripts. RESULTS AND DISCUSSION: 152 manuscripts were identified as relating to the seasonality of malaria transmission, deaths due to malaria or the population dynamics of mosquito vectors of malaria. Among these, there were 126 statistical analyses and 31 mechanistic analyses (some manuscripts did both). DISCUSSION: Identified relationships between temporal patterns in malaria and climatological drivers of malaria varied greatly across the globe, with different drivers appearing important in different locations. Although commonly studied drivers of malaria such as temperature and rainfall were often found to significantly influence transmission, the lags between a weather event and a resulting change in malaria transmission also varied greatly by location. CONCLUSIONS: The contradicting results of studies using similar data and modelling approaches from similar locations as well as the confounding nature of climatological covariates underlines the importance of a multi-faceted modelling approach that attempts to capture seasonal patterns at both small and large spatial scales. PMID- 26370143 TI - Increased genetic gains in sheep, beef and dairy breeding programs from using female reproductive technologies combined with optimal contribution selection and genomic breeding values. AB - BACKGROUND: Female reproductive technologies such as multiple ovulation and embryo transfer (MOET) and juvenile in vitro embryo production and embryo transfer (JIVET) can boost rates of genetic gain but they can also increase rates of inbreeding. Inbreeding can be managed using the principles of optimal contribution selection (OCS), which maximizes genetic gain while placing a penalty on the rate of inbreeding. We evaluated the potential benefits and synergies that exist between genomic selection (GS) and reproductive technologies under OCS for sheep and cattle breeding programs. METHODS: Various breeding program scenarios were simulated stochastically including: (1) a sheep breeding program for the selection of a single trait that could be measured either early or late in life; (2) a beef breeding program with an early or late trait; and (3) a dairy breeding program with a sex limited trait. OCS was applied using a range of penalties (severe to no penalty) on co-ancestry of selection candidates, with the possibility of using multiple ovulation and embryo transfer (MOET) and/or juvenile in vitro embryo production and embryo transfer (JIVET) for females. Each breeding program was simulated with and without genomic selection. RESULTS: All breeding programs could be penalized to result in an inbreeding rate of 1 % increase per generation. The addition of MOET to artificial insemination or natural breeding (AI/N), without the use of GS yielded an extra 25 to 60 % genetic gain. The further addition of JIVET did not yield an extra genetic gain. When GS was used, MOET and MOET + JIVET programs increased rates of genetic gain by 38 to 76 % and 51 to 81 % compared to AI/N, respectively. CONCLUSIONS: Large increases in genetic gain were found across species when female reproductive technologies combined with genomic selection were applied and inbreeding was managed, especially for breeding programs that focus on the selection of traits measured late in life or that are sex-limited. Optimal contribution selection was an effective tool to optimally allocate different combinations of reproductive technologies. Applying a range of penalties to co-ancestry of selection candidates allows a comprehensive exploration of the inbreeding vs. genetic gain space. PMID- 26370146 TI - Targeting the reconsolidation of extinction memories: a novel potential strategy to treat anxiety disorders. PMID- 26370144 TI - Alteration by p11 of mGluR5 localization regulates depression-like behaviors. AB - Mood disorders and antidepressant therapy involve alterations of monoaminergic and glutamatergic transmission. The protein S100A10 (p11) was identified as a regulator of serotonin receptors, and it has been implicated in the etiology of depression and in mediating the antidepressant actions of selective serotonin reuptake inhibitors. Here we report that p11 can also regulate depression-like behaviors via regulation of a glutamatergic receptor in mice. p11 directly binds to the cytoplasmic tail of metabotropic glutamate receptor 5 (mGluR5). p11 and mGluR5 mutually facilitate their accumulation at the plasma membrane, and p11 increases cell surface availability of the receptor. Whereas p11 overexpression potentiates mGluR5 agonist-induced calcium responses, overexpression of mGluR5 mutant, which does not interact with p11, diminishes the calcium responses in cultured cells. Knockout of mGluR5 or p11 specifically in glutamatergic neurons in mice causes depression-like behaviors. Conversely, knockout of mGluR5 or p11 in GABAergic neurons causes antidepressant-like behaviors. Inhibition of mGluR5 with an antagonist, 2-methyl-6-(phenylethynyl)pyridine (MPEP), induces antidepressant-like behaviors in a p11-dependent manner. Notably, the antidepressant-like action of MPEP is mediated by parvalbumin-positive GABAergic interneurons, resulting in a decrease of inhibitory neuronal firing with a resultant increase of excitatory neuronal firing. These results identify a molecular and cellular basis by which mGluR5 antagonism achieves its antidepressant-like activity. PMID- 26370145 TI - From impulses to maladaptive actions: the insula is a neurobiological gate for the development of compulsive behavior. AB - Impulsivity is an endophenotype of vulnerability for compulsive behaviors. However, the neural mechanisms whereby impulsivity facilitates the development of compulsive disorders, such as addiction or obsessive compulsive disorder, remain unknown. We first investigated, in rats, anatomical and functional correlates of impulsivity in the anterior insular (AI) cortex by measuring both the thickness of, and cellular plasticity markers in, the AI with magnetic resonance imaging and in situ hybridization of the immediate early gene zif268, respectively. We then investigated the influence of bilateral AI cortex lesions on the high impulsivity trait, as measured in the five-choice serial reaction time task (5 CSRTT), and the associated propensity to develop compulsivity as measured by high drinking levels in a schedule-induced polydipsia procedure (SIP). We demonstrate that the AI cortex causally contributes to individual vulnerability to impulsive compulsive behavior in rats. Motor impulsivity, as measured by premature responses in the 5-CSRTT, was shown to correlate with the thinness of the anterior region of the insular cortex, in which highly impulsive (HI) rats expressed lower zif268 mRNA levels. Lesions of AI reduced impulsive behavior in HI rats, which were also highly susceptible to develop compulsive behavior as measured in a SIP procedure. AI lesions also attenuated both the development and the expression of SIP. This study thus identifies the AI as a novel neural substrate of maladaptive impulse control mechanisms that may facilitate the development of compulsive disorders. PMID- 26370148 TI - A pilot single-blind multicentre randomized controlled trial to evaluate the potential benefits of computer-assisted arm rehabilitation gaming technology on the arm function of children with spastic cerebral palsy. AB - OBJECTIVE: To evaluate the potential benefits of computer-assisted arm rehabilitation gaming technology on arm function of children with spastic cerebral palsy. DESIGN: A single-blind randomized controlled trial design. Power calculations indicated that 58 children would be required to demonstrate a clinically important difference. SETTING: Intervention was home-based; recruitment took place in regional spasticity clinics. PARTICIPANTS: A total of 15 children with cerebral palsy aged five to 12 years were recruited; eight to the device group. INTERVENTIONS: Both study groups received 'usual follow-up treatment' following spasticity treatment with botulinum toxin; the intervention group also received a rehabilitation gaming device. MAIN MEASURES: ABILHAND-kids and Canadian Occupational Performance Measure were performed by blinded assessors at baseline, six and 12 weeks. RESULTS: An analysis of covariance showed no group differences in mean ABILHAND-kids scores between time points. A non-parametric analysis of variance on Canadian Occupational Performance Measure scores showed a statistically significant improvement across time points (chi2 (2,15) = 6.778, p = 0.031), but this improvement did not reach minimal clinically important difference. Mean daily device use was seven minutes. Recruitment did not reach target owing to unanticipated staff shortages in clinical services. Feedback from children and their families indicated that the games were not sufficiently engaging to promote sufficient use that was likely to result in functional benefits. CONCLUSION: This study suggests that computer-assisted arm rehabilitation gaming does not benefit arm function, but a Type II error cannot be ruled out. PMID- 26370149 TI - Familial determinants of current smoking among adolescents of Lithuania: a cross sectional survey 2014. AB - BACKGROUND: Understanding the role of the family in shaping adolescent health risk behaviours has recently been given increased attention. This study investigated association between current smoking and a range of familial factors in a representative sample of Lithuanian adolescents. METHODS: Study subjects (N = 3696) were adolescents aged 13- and 15-years from the schools in Lithuania who were surveyed in Spring 2014 according to the methodology of the cross-national Health Behaviour in School-aged Children (HBSC). A standard HBSC international questionnaire was translated into Lithuanian and used anonymously to obtain information about current smoking patterns and family life (family structure, quality of communication in family, parental monitoring, bonding, parenting style, family time, etc.). Logistic regression was used to assess association between smoking and familial variables. RESULTS: The prevalence of current smoking was 16.5 % (20.8 % in boys and 11.9 % in girls; P < 0.001). Adjusting for gender, age and family affluence, adolescents from non-intact families were significantly more likely to be current smokers (OR = 2.10; 95 % CI: 1.74-2.54) compared with intact families. Five independent familial factors were significantly related to increased risk for adolescent smoking: low maternal monitoring (OR = 2.79; 95 % CI: 1.98-3.92), low satisfaction with family relationships (OR = 1.89; 95 % CI: 1.27-2.83), low school-related parental support (OR = 1.40; 95 % CI: 1.01-1.95), easy communication with the father (OR = 0.56; 95 % CI: 0.38-0.80) and often use of electronic media for communication with parents (OR = 0.66; 95 % CI: 0.50-0.88). The last two determinants showed an inverse effect than it was hypothesized. CONCLUSION: Higher prevalence of smoking among adolescents of Lithuania is associated with a non- intact family structure as well as weaker parental support and bonding. Family life practices are critical components to be incorporated in prevention and intervention programs for adolescent smoking in Lithuania. PMID- 26370150 TI - A study on African animal trypanosomosis in four areas of Senegal. AB - In Senegal, several areas provide great potential for agriculture and animal production, but African animal trypanosomosis (AAT) is one of the major constraints to the development of more effective livestock production systems. A study was conducted to assess the current situation of AAT in this country. Surveys were carried out between June 2011 and September 2012 in four different areas: Dakar, Sine Saloum, Kedougou region and Basse Casamance in several animal species: dogs (152), donkeys (23), horses (63), sheep (43), goats (52) and cattle (104), distributed in the four sites. Molecular tools (PCR) indicated 3.4% positive animals including dogs, donkeys, a goat and cattle. The savannah type of Trypanosoma congolense Broden, 1904 (53% of positive cases) and the forest type of T. congolense (subgenus Nannomonas Hoare, 1964) were predominant. Trypanosoma vivax Ziemann, 1905 (subgenus Duttonella Chalmers, 1918) was only present in one animal and no trypanosome of the subgenus Trypanozoon Luhe, 1906 was found. Half of the positive cases were detected in Sine Saloum, where T. congolense savannah type was predominant, and the other half in Basse Casamance, where T. congolense forest-type was predominant; no cases were found in Dakar or in the Kedougou region. A high risk of infection in dogs with T. congolense savannah-type was shown in Sine Saloum, requiring prevention and control of dogs in this area. The involvement of tsetse flies in the transmission of T. congolense in Sine Saloum and Basse Casamance is discussed. PMID- 26370147 TI - Genetic and functional analyses demonstrate a role for abnormal glycinergic signaling in autism. AB - Autism spectrum disorder (ASD) is a common neurodevelopmental condition characterized by marked genetic heterogeneity. Recent studies of rare structural and sequence variants have identified hundreds of loci involved in ASD, but our knowledge of the overall genetic architecture and the underlying pathophysiological mechanisms remains incomplete. Glycine receptors (GlyRs) are ligand-gated chloride channels that mediate inhibitory neurotransmission in the adult nervous system but exert an excitatory action in immature neurons. GlyRs containing the alpha2 subunit are highly expressed in the embryonic brain, where they promote cortical interneuron migration and the generation of excitatory projection neurons. We previously identified a rare microdeletion of the X-linked gene GLRA2, encoding the GlyR alpha2 subunit, in a boy with autism. The microdeletion removes the terminal exons of the gene (GLRA2(Deltaex8-9)). Here, we sequenced 400 males with ASD and identified one de novo missense mutation, p.R153Q, absent from controls. In vitro functional analysis demonstrated that the GLRA2(Deltaex8)(-)(9) protein failed to localize to the cell membrane, while the R153Q mutation impaired surface expression and markedly reduced sensitivity to glycine. Very recently, an additional de novo missense mutation (p.N136S) was reported in a boy with ASD, and we show that this mutation also reduced cell surface expression and glycine sensitivity. Targeted glra2 knockdown in zebrafish induced severe axon-branching defects, rescued by injection of wild type but not GLRA2(Deltaex8-9) or R153Q transcripts, providing further evidence for their loss of-function effect. Glra2 knockout mice exhibited deficits in object recognition memory and impaired long-term potentiation in the prefrontal cortex. Taken together, these results implicate GLRA2 in non-syndromic ASD, unveil a novel role for GLRA2 in synaptic plasticity and learning and memory, and link altered glycinergic signaling to social and cognitive impairments. PMID- 26370151 TI - Antiviral Activity of Graphene Oxide: How Sharp Edged Structure and Charge Matter. AB - Graphene oxide and its derivatives have been widely explored for their antimicrobial properties due to their high surface-to-volume ratios and unique chemical and physical properties. However, little information is available on their effects on viruses. In this study, we report the broad-spectrum antiviral activity of GO against pseudorabies virus (PRV, a DNA virus) and porcine epidemic diarrhea virus (PEDV, an RNA virus). Our results showed that GO significantly suppressed the infection of PRV and PEDV for a 2 log reduction in virus titers at noncytotoxic concentrations. The potent antiviral activity of both GO and rGO can be attributed to the unique single-layer structure and negative charge. First, GO exhibited potent antiviral activity when conjugated with PVP, a nonionic polymer, but not when conjugated with PDDA, a cationic polymer. Additionally, the precursors Gt and GtO showed much weaker antiviral activity than monolayer GO and rGO, suggesting that the nanosheet structure is important for antiviral properties. Furthermore, GO inactivated both viruses by structural destruction prior to viral entry. The overall results suggest the potential of graphene oxide as a novel promising antiviral agent with a broad and potent antiviral activity. PMID- 26370152 TI - Multifaceted roles for thymine DNA glycosylase in embryonic development and human carcinogenesis. AB - Thymine DNA glycosylase (TDG) is a multifunctional protein that plays important roles in DNA repair, DNA demethylation, and transcriptional regulation. These diverse functions make TDG a unique enzyme in embryonic development and carcinogenesis. This review discusses the molecular function of TDG in human cancers and the previously unrecognized value of TDG as a potential target for drug therapy. PMID- 26370153 TI - Radiation exposure of the interventional radiologist during percutaneous biopsy using a multiaxis interventional C-arm CT system with 3D laser guidance: a phantom study. AB - OBJECTIVE: Evaluation of absolute radiation exposure values for interventional radiologists (IRs) using a multiaxis interventional flat-panel C-arm cone beam CT (CBCT) system with three-dimensional laser guidance for biopsy in a triple modality, abdominal phantom. METHODS: In the phantom, eight lesions were punctured in two different angles (in- and out-of-plane) using CBCT. One C-arm CT scan was performed to plan the intervention and one for post-procedural evaluation. Thermoluminescent dosemeters (TLDs) were used for dose measurement at the level of the eye lens, umbilicus and ankles on a pole representing the IRs. All measurements were performed without any lead protection. In addition, the dose-area product (DAP) and air kerma at the skin entrance point was documented. RESULTS: Mean radiation values of all TLDs were 190 uSv for CBCT (eye lens: 180 uS, umbilicus: 230 uSv, ankle: 150 uSv) without a significant difference (p > 0.005) between in- and out-of-plane biopsies. In terms of radiation exposure of the phantom, the mean DAP was not statistically significantly different (p > 0.05) for in- and out-of-plane biopsies. Fluoroscopy showed a mean DAP of 7 or 6 MUGym(2), respectively. C-arm CT showed a mean DAP of 5150 or 5130 MUGym(2), respectively. CONCLUSION: In our setting, the radiation dose to the IR was distinctly high using CBCT. For dose reduction, it is advisable to pay attention to lead shielding, to increase the distance to the X-ray source and to leave the intervention suite for C-arm CT scans. ADVANCES IN KNOWLEDGE: The results indicate that using modern navigation tools and CBCT can be accompanied with a relative high radiation dose for the IRs since detector angulation can make the use of proper lead shielding difficult. PMID- 26370154 TI - miRNAs regulated overexpression of ryanodine receptor is involved in chlorantraniliprole resistance in Plutella xylostella (L.). AB - The amino acid mutations in ryanodine receptor (RyR) and elevated activity of detoxification enzymes have been associated with the diamide insecticide resistance in the diamondback moth, Plutella xylostella (L.). The up-regulation of P. xylostella RyR mRNA (PxRyR) expression has also been reported in field populations of different graphical origin. However, whether the up-regulation of PxRyR is involved in diamide resistance remains unknown. In this paper, 2.28- to 4.14-fold higher expression of PxRyR was detected in five field collected resistant populations, compared to that in a susceptible population. The expression of PxRyR was up-regulated 5.0- and 7.2-fold, respectively, after P. xylostella was treated with LC50 and LC75 of chlorantraniliprole for 12 h. Suppression of PxRyR using RNA interference restored the toxicity of chlorantraniliprole against the fourth instar larvae from the resistant population. More importantly, the expression of PxRyR is regulated by two miRNAs, miR-7a and miR-8519. These findings provide an empirical evidence of the involvement of miRNAs in the regulation of insecticide resistance, and shed light on the novel targets for the sustainable management of this devastating insect pest. PMID- 26370155 TI - MRI Scanners Guide Therapy to Tumors. AB - A new study shows that MRI scanners can direct magnetically labeled macrophages bearing an oncolytic virus toward primary and metastatic tumors in mice. Researchers hope this approach, called magnetic resonance targeting, can be scaled for use in humans, to improve the delivery of cell-based cancer therapy. PMID- 26370157 TI - Fertility preservation options in breast cancer patients. AB - The purpose of this review is to analyse current options for fertility preservation in young women with breast cancer (BC). Considering an increasing number of BC survivors, owing to improvements in cancer treatment and delaying of childbearing, fertility preservation appears to be an important issue. Current fertility preservation options in BC survivors range from well-established standard techniques to experimental or investigational interventions. Among the standard options, random-start ovarian stimulation protocol represents a new technique, which significantly decreases the total time of the in vitro fertilisation cycle. However, in patients with oestrogen-sensitive tumours, stimulation protocols using aromatase inhibitors are currently preferred over tamoxifen regimens. Cryopreservation of embryos and oocytes are nowadays deemed the most successful techniques for fertility preservation in BC patients. GnRH agonists during chemotherapy represent an experimental method for fertility preservation due to conflicting long-term outcome results regarding its safety and efficacy. Cryopreservation of ovarian tissue, in vitro maturation of immature oocytes and other strategies are considered experimental and should only be offered within the context of a clinical trial. An early pretreatment referral to reproductive endocrinologists and oncologists should be suggested to young BC women at risk of infertility, concerning the risks and benefits of fertility preservation options. PMID- 26370158 TI - Is revascularization of immature permanent teeth an effective and reproducible technique? AB - BACKGROUND: Revascularization has been proposed as an improved alternative treatment for irreversibly damaged pulp of immature teeth as it has been shown to preserve the potential for continued root growth in treated teeth. AIM: To review clinical cases of revascularization in humans to evaluate their utility and reproducibility. MATERIAL AND METHODS: A structured electronic search of scientific articles published between 2001 and 2014 was carried out using the following keywords: 'pulp revascularization', 'pulp revitalization' and/or 'immature tooth'. Clinical revascularization cases conducted on human subjects were selected, reviewed and organized into two charts including patient information, diagnostic information, treatment and results in follow-up visits. RESULTS: Ninety-seven of 101 teeth (96.0%) were successfully treated with the revascularization technique. The range of technique variations available for irrigation, disinfection and blood clot induction have a negligible impact on the clinical outcome variables tested in our analysis. During the follow-up visits, apical closure was detected in fewer cases (55.4%) as compared to the other apexogenesis phenomena (increased root length, 76.2%; increased root width, 79.2%). CONCLUSIONS: The review shows that the revascularization technique showed marked increase in the root length, width and apical closure in the cases that were reported independently of clinical variables such as operator and material selection and individual differences in protocols. PMID- 26370156 TI - RICTOR Amplification Defines a Novel Subset of Patients with Lung Cancer Who May Benefit from Treatment with mTORC1/2 Inhibitors. AB - We identified amplification of RICTOR, a key component of the mTOR complex 2 (mTORC2), as the sole actionable genomic alteration in an 18-year-old never smoker with lung adenocarcinoma. Amplification of RICTOR occurs in 13% of lung cancers (1,016 cases) in The Cancer Genome Atlas and at a similar frequency in an independent cohort of 1,070 patients identified by genomic profiling. In the latter series, 11% of cases harbored RICTOR amplification as the only relevant genomic alteration. Its oncogenic roles were suggested by decreased lung cancer cell growth both in vitro and in vivo with RICTOR ablation, and the transforming capacity of RICTOR in a Ba/F3-cell system. The mTORC1/2 inhibitors were significantly more active against RICTOR-amplified lung cancer cells as compared with other agents targeting the PI3K-AKT-mTOR pathway. Moreover, an association between RICTOR amplification and sensitivities to mTORC1/2 inhibitors was observed. The index patient has been treated with mTORC1/2 inhibitors that led to tumor stabilization for more than 18 months. SIGNIFICANCE: RICTOR amplification may define a novel and unique molecular subset of patients with lung cancer who may benefit from treatment with mTORC1/2 inhibitors. PMID- 26370159 TI - Complete mitochondrial genome of the Sepiella maindroni (Sepioidea: Sepiidae). AB - The complete mitochondrial genome of the Sepiella maindroni has been sequenced. The mitochondrial genome is 16 170 bp in length, containing 13 protein-coding genes, two ribosomal RNA genes, and 22 transfer RNA genes. The gene order and composition of S. maindroni mitochondrial genome was similar to that of most other invertebrates. The overall nucleotides base composition of the heavy strand is A (39.91%), G (8.06% of), C (16.52%), and T (35.50%), with highly A + T bias of 75.41%. Seen from the phylogenetic tree, S. maindroni, Sepiella japonica, and Sepiella inermis from the same genus (Sepiella) clustered into one branch. PMID- 26370160 TI - Midwife-led continuity models versus other models of care for childbearing women. AB - BACKGROUND: Midwives are primary providers of care for childbearing women around the world. However, there is a lack of synthesised information to establish whether there are differences in morbidity and mortality, effectiveness and psychosocial outcomes between midwife-led continuity models and other models of care. OBJECTIVES: To compare midwife-led continuity models of care with other models of care for childbearing women and their infants. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2015) and reference lists of retrieved studies. SELECTION CRITERIA: All published and unpublished trials in which pregnant women are randomly allocated to midwife led continuity models of care or other models of care during pregnancy and birth. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. MAIN RESULTS: We included 15 trials involving 17,674 women. We assessed the quality of the trial evidence for all primary outcomes (i.e., regional analgesia (epidural/spinal), caesarean birth, instrumental vaginal birth (forceps/vacuum), spontaneous vaginal birth, intact perineum, preterm birth (less than 37 weeks) and overall fetal loss and neonatal death (fetal loss was assessed by gestation using 24 weeks as the cut-off for viability in many countries) using the GRADE methodology: All primary outcomes were graded as of high quality.For the primary outcomes, women who had midwife-led continuity models of care were less likely to experience regional analgesia (average risk ratio (RR) 0.85, 95% confidence interval (CI) 0.78 to 0.92; participants = 17,674; studies = 14; high quality), instrumental vaginal birth (average RR 0.90, 95% CI 0.83 to 0.97; participants = 17,501; studies = 13; high quality), preterm birth less than 37 weeks (average RR 0.76, 95% CI 0.64 to 0.91; participants = 13,238; studies = 8; high quality) and less overall fetal/neonatal death (average RR 0.84, 95% CI 0.71 to 0.99; participants = 17,561; studies = 13; high quality evidence). Women who had midwife-led continuity models of care were more likely to experience spontaneous vaginal birth (average RR 1.05, 95% CI 1.03 to 1.07; participants = 16,687; studies = 12; high quality). There were no differences between groups for caesarean births or intact perineum.For the secondary outcomes, women who had midwife-led continuity models of care were less likely to experience amniotomy (average RR 0.80, 95% CI 0.66 to 0.98; participants = 3253; studies = 4), episiotomy (average RR 0.84, 95% CI 0.77 to 0.92; participants = 17,674; studies = 14) and fetal loss/neonatal death before 24 weeks (average RR 0.81, 95% CI 0.67 to 0.98; participants = 15,645; studies = 11). Women who had midwife-led continuity models of care were more likely to experience no intrapartum analgesia/anaesthesia (average RR 1.21, 95% CI 1.06 to 1.37; participants = 10,499; studies = 7), have a longer mean length of labour (hours) (mean difference (MD) 0.50, 95% CI 0.27 to 0.74; participants = 3328; studies = 3) and more likely to be attended at birth by a known midwife (average RR 7.04, 95% CI 4.48 to 11.08; participants = 6917; studies = 7). There were no differences between groups for fetal loss or neonatal death more than or equal to 24 weeks, induction of labour, antenatal hospitalisation, antepartum haemorrhage, augmentation/artificial oxytocin during labour, opiate analgesia, perineal laceration requiring suturing, postpartum haemorrhage, breastfeeding initiation, low birthweight infant, five-minute Apgar score less than or equal to seven, neonatal convulsions, admission of infant to special care or neonatal intensive care unit(s) or in mean length of neonatal hospital stay (days).Due to a lack of consistency in measuring women's satisfaction and assessing the cost of various maternity models, these outcomes were reported narratively. The majority of included studies reported a higher rate of maternal satisfaction in midwife-led continuity models of care. Similarly, there was a trend towards a cost-saving effect for midwife-led continuity care compared to other care models. AUTHORS' CONCLUSIONS: This review suggests that women who received midwife-led continuity models of care were less likely to experience intervention and more likely to be satisfied with their care with at least comparable adverse outcomes for women or their infants than women who received other models of care.Further research is needed to explore findings of fewer preterm births and fewer fetal deaths less than 24 weeks, and overall fetal loss/neonatal death associated with midwife-led continuity models of care. PMID- 26370161 TI - Impact of bevacizumab in combination with erlotinib on EGFR-mutated non-small cell lung cancer xenograft models with T790M mutation or MET amplification. AB - Erlotinib (ERL), an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, shows notable efficacy against non-small cell lung cancer (NSCLC) harboring EGFR mutations. Bevacizumab (BEV), a humanized monoclonal antibody to vascular endothelial cell growth factor (VEGF), in combination with ERL (BEV+ERL) significantly extended progression-free survival in patients with EGFR-mutated NSCLC compared with ERL alone. However, the efficacy of BEV+ERL against EGFR mutated NSCLC harboring T790M mutation or MET amplification, is unclear. Here, we examined the antitumor activity of BEV+ERL in four xenograft models of EGFR mutated NSCLC (three harboring ERL resistance mutations). In the HCC827 models (exon 19 deletion: DEL), ERL significantly inhibited tumor growth by blocking EGFR signal transduction. Although there was no difference between ERL and BEV+ERL in maximum tumor growth inhibition, BEV+ERL significantly suppressed tumor regrowth during a drug-cessation period. In the HCC827-EPR model (DEL+T790M) and HCC827-vTR model (DEL+MET amplification), ERL reduced EGFR signal transduction and showed less pronounced but still significant tumor growth inhibition than in the HCC827 model. In these models, tumor growth inhibition was significantly stronger with BEV+ERL than with each single agent. In the NCI-H1975 model (L858R+T790M), ERL did not inhibit growth or EGFR signal transduction, and BEV+ERL did not inhibit growth more than BEV. BEV alone significantly decreased microvessel density in each tumor. In conclusion, addition of BEV to ERL did not enhance antitumor activity in primarily ERL-resistant tumors with T790M mutation; however, BEV+ERL enhanced antitumor activity in T790M mutation- or MET amplification-positive tumors as long as their growth remained significantly suppressed by ERL. PMID- 26370163 TI - Comparative analysis of Staphylococcus epidermidis strains utilizing quantitative and cell surface shaving proteomics. AB - Staphylococcus epidermidis is an opportunistic pathogen that is an emerging risk factor in hospitals worldwide and is often difficult to eradicate as virulent strains produce a protective biofilm matrix. We utilized cell shaving proteomics to profile surface-exposed proteins from two fully genome sequenced S. epidermidis strains: the avirulent, non-biofilm forming ATCC12228 and the virulent, strongly adherent biofilm forming ATCC35984 (RP62A). A false positive control strategy was employed to calculate the probabilities of proteins being truly surface-exposed. A total of 78 surface-exposed proteins were identified, of which only 19 proteins were common to ATCC12228 and RP62A, and which thus represents the core surfaceome. S. epidermidis RP62A displayed additional proteins involved in biofilm formation (cell wall-associated Bhp and intercellular adhesion protein IcaB), surface antigenicity, peptidoglycan biosynthesis and antibiotic resistance. We concurrently profiled whole cell proteomes of the two strains using iTRAQ quantitation and LC-MS/MS. A total of 1610 proteins were confidently identified (representing 64% of the theoretical S. epidermidis proteome). One hundred and ninety one proteins were differentially abundant between strains. Proteins associated with RP62A were clustered into functions including Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-mediated defense, sulfate assimilation, antibiotic resistance and biofilm formation. Validation of the sulfate assimilation and cysteine/methionine biosynthesis pathways showed RP62A contained elevated levels (~25% increase) of methionine that are likely linked to biofilm formation. BIOLOGICAL SIGNIFICANCE: Cell shaving and quantitative proteomics identified proteins associated with a biofilm-forming, virulent strain of S. epidermidis (RP62A). These proteins show RP62A maintains an active CRISPR-mediated defense, as well as heightened antibiotic resistance in comparison to a non-virulent, non-biofilm forming strain. Increased abundances of sulfate assimilation proteins lead to elevated intracellular methionine. Proteins and their exposed peptides identified on the surface of S. epidermidis RP62A may be useful vaccine antigens in clinical settings if administered in at-risk patients prior to surgical implantations. PMID- 26370162 TI - Gad1 mRNA as a reliable indicator of altered GABA release from orexigenic neurons in the hypothalamus. AB - The strength of gamma-aminobutyric acid (GABA)-mediated inhibitory synaptic input is a principle determinant of neuronal activity. However, because of differences in the number of GABA afferent inputs and the sites of synapses, it is difficult to directly assay for altered GABA transmission between specific cells. The present study tested the hypothesis that the level of mRNA for the GABA synthetic enzyme glutamate decarboxylase (GAD) can provide a reliable proxy for GABA release. This was tested in a mouse hypothalamic circuit important in the regulation of energy balance. Fluorescent in situ hybridization results show that the expression of Gad1 mRNA (encoding the GAD67 enzyme) was increased in hypothalamic neuropeptide Y/agouti-related peptide (NPY/AgRP) neurons after an overnight fast, consistent with the ability of GABA from these neurons to stimulate food intake. Optogenetic studies confirmed that the observed increase in Gad1 mRNA correlated with an increase in the probability of GABA release from NPY/AgRP neurons onto downstream proopiomelanocortin neurons. Likewise, there was an increase in the readily releasable pool of GABA in NPY/AgRP neurons. Selective inhibition of GAD activity in NPY/AgRP neurons decreased GABA release, indicating that GAD67 activity, which is largely dictated by expression level, is a key determinant of GABA release. Altogether, it appears that Gad expression may be a reliable proxy of altered GABAergic transmission. Examining changes in Gad mRNA as a proxy for GABA release may be particularly helpful when the downstream targets are not known or when limited tools exist for detecting GABA release at a particular synapse. PMID- 26370164 TI - Urine proteome analysis in Dent's disease shows high selective changes potentially involved in chronic renal damage. AB - Definition of the urinary protein composition would represent a potential tool for diagnosis in many clinical conditions. The use of new proteomic technologies allows detection of genetic and post-trasductional variants that increase sensitivity of the approach but complicates comparison within a heterogeneous patient population. Overall, this limits research of urinary biomarkers. Studying monogenic diseases are useful models to address this issue since genetic variability is reduced among first- and second-degree relatives of the same family. We applied this concept to Dent's disease, a monogenic condition characterised by low-molecular-weight proteinuria that is inherited following an X-linked trait. Results are presented here on a combined proteomic approach (LC mass spectrometry, Western blot and zymograms for proteases and inhibitors) to characterise urine proteins in a large family (18 members, 6 hemizygous patients, 6 carrier females, and 6 normals) with Dent's diseases due to the 1070G>T mutation of the CLCN5. Gene ontology analysis on more than 1000 proteins showed that several clusters of proteins characterised urine of affected patients compared to carrier females and normal subjects: proteins involved in extracellular matrix remodelling were the major group. Specific analysis on metalloproteases and their inhibitors underscored unexpected mechanisms potentially involved in renal fibrosis. BIOLOGICAL SIGNIFICANCE: Studying with new-generation techniques for proteomic analysis of the members of a large family with Dent's disease sharing the same molecular defect allowed highly repetitive results that justify conclusions. Identification in urine of proteins actively involved in interstitial matrix remodelling poses the question of active anti fibrotic drugs in Dent's patients. PMID- 26370165 TI - The Diversity of Pea Microsymbionts in Various Types of Soils and Their Effects on Plant Host Productivity. AB - The growth and yield of peas cultivated on eight different soils, as well as the diversity of pea microsymbionts derived from these soils were investigated in the present study. The experimental plot was composed of soils that were transferred from different parts of Poland more than a century ago. The soils were located in direct vicinity of each other in the experimental plot. All soils examined contained pea microsymbionts, which were suggested to belong to Rhizobium leguminosarum sv. viciae based on the nucleotide sequence of the partial 16S rRNA gene. PCR-RFLP analyses of the 16S-23S rRNA gene ITS region and nodD alleles revealed the presence of numerous and diversified groups of pea microsymbionts and some similarities between the tested populations, which may have been the result of the spread or displacement of strains. However, most populations retained their own genetic distinction, which may have been related to the type of soil. Most of the tested populations comprised low-effective strains for the promotion of pea growth. No relationships were found between the characteristics of soil and symbiotic effectiveness of rhizobial populations; however, better seed yield was obtained for soil with medium biological productivity inhabited by high-effective rhizobial populations than for soil with high agricultural quality containing medium-quality pea microsymbionts, and these results showed the importance of symbiosis for plant hosts. PMID- 26370166 TI - Characterization of the Skin Microbiota in Italian Stream Frogs (Rana italica) Infected and Uninfected by a Cutaneous Parasitic Disease. AB - In human and wildlife populations, the natural microbiota plays an important role in health maintenance and the prevention of emerging infectious diseases. In amphibians, infectious diseases have been closely associated with population decline and extinction worldwide. Skin symbiont communities have been suggested as one of the factors driving the different susceptibilities of amphibians to diseases. The activity of the skin microbiota of amphibians against fungal pathogens, such as Batrachochytrium dendrobatidis, has been examined extensively, whereas its protective role towards the cutaneous infectious diseases caused by Amphibiocystidium parasites has not yet been elucidated in detail. In the present study, we investigated, for the first time, the cutaneous microbiota of the Italian stream frog (Rana italica) and characterized the microbial assemblages of frogs uninfected and infected by Amphibiocystidium using the Illumina next generation sequencing of 16S rRNA gene fragments. A total of 629 different OTUs belonging to 16 different phyla were detected. Bacterial populations shared by all individuals represented only one fifth of all OTUs and were dominated by a small number of OTUs. Statistical analyses based on Bray-Curtis distances showed that uninfected and infected specimens had distinct cutaneous bacterial community structures. Phylotypes belonging to the genera Janthinobacterium, Pseudomonas, and Flavobacterium were more abundant, and sometimes almost exclusively present, in uninfected than in infected specimens. These bacterial populations, known to exhibit antifungal activity in amphibians, may also play a role in protection against cutaneous infectious diseases caused by Amphibiocystidium parasites. PMID- 26370168 TI - ERP C1 is top-down modulated by orientation perceptual learning. AB - The brain site of perceptual learning has been frequently debated. Recent psychophysical evidence for complete learning transfer to new retinal locations and orientations/directions suggests that perceptual learning may mainly occur in high-level brain areas. Contradictorily, ERP C1 changes associated with perceptual learning are cited as evidence for training-induced plasticity in the early visual cortex. However, C1 can be top-down modulated, which suggests the possibility that C1 changes may result from top-down modulation of the early visual cortex by high-level perceptual learning. To single out the potential top down impact, we trained observers with a peripheral orientation discrimination task and measured C1 changes at an untrained diagonal quadrant location where learning transfer was previously known to be significant. Our assumption was that any C1 changes at this untrained location would indicate top-down modulation of the early visual cortex, rather than plasticity in the early visual cortex. The expected learning transfer was indeed accompanied with significant C1 changes. Moreover, C1 changes were absent in an untrained shape discrimination task with the same stimuli. We conclude that ERP C1 can be top-down modulated in a task specific manner by high-level perceptual learning, so that C1 changes may not necessarily indicate plasticity in the early visual cortex. Moreover, learning transfer and associated C1 changes may indicate that learning-based top-down modulation can be remapped to early visual cortical neurons at untrained locations to enable learning transfer. PMID- 26370167 TI - Alpha-band EEG activity in perceptual learning. AB - In studies of perceptual learning (PL), subjects are typically highly trained across many sessions to achieve perceptual benefits on the stimuli in those tasks. There is currently significant debate regarding what sources of brain plasticity underlie these PL-based learning improvements. Here we investigate the hypothesis that PL, among other mechanisms, leads to task automaticity, especially in the presence of the trained stimuli. To investigate this hypothesis, we trained participants for eight sessions to find an oriented target in a field of near-oriented distractors and examined alpha-band activity, which modulates with attention to visual stimuli, as a possible measure of automaticity. Alpha-band activity was acquired via electroencephalogram (EEG), before and after training, as participants performed the task with trained and untrained stimuli. Results show that participants underwent significant learning in this task (as assessed by threshold, accuracy, and reaction time improvements) and that alpha power increased during the pre-stimulus period and then underwent greater desynchronization at the time of stimulus presentation following training. However, these changes in alpha-band activity were not specific to the trained stimuli, with similar patterns of posttraining alpha power for trained and untrained stimuli. These data are consistent with the view that participants were more efficient at focusing resources at the time of stimulus presentation and are consistent with a greater automaticity of task performance. These findings have implications for PL, as transfer effects from trained to untrained stimuli may partially depend on differential effort of the individual at the time of stimulus processing. PMID- 26370169 TI - Ultrastructural and functional adaptations of the female reproductive system in the family Heterozerconidae (Acari, Anactinotrichida, Gamasida, Heterozerconina) and implications for the systematic position of the group. AB - Heterozerconidae is a poorly known, early derived mite family belonging to Heterozerconina (Monogynaspida, Gamasida (= Mesostigmata)). The systematic position of the family is still controversial and little is known about the biology and anatomy of the taxon. In this paper, the gross anatomy, ultrastructure and functional morphology of the female reproductive system are described comparing genera from different geographic areas. The occurence of podospermy (i.e. the use of a sperm transfer process carried by the fixed digit of the male chelicerae to inseminate females through secondary insemination pores instead of through the oviporus) as insemination mode in this family was documented. Nevertheless, morphological and functional evidence in the reproductive system of the females supports the idea that, in the same family, more than one insemination mode is present: some genera are plesiomorphically tocospemic (i.e. insemination through the oviporus) while others switched to podospermy. Such discovery is of fundamental importance for the determination of the relationship between the family Heterozerconidae and the family Discozerconidae, both belonging tentatively to Heterozerconina and for the phylogenetic position of the Heterozerconina among Gamasida. PMID- 26370170 TI - Key Approach to Expanding the Less Invasive Off-Pump Coronary Artery Bypass Grafting Procedure Worldwide. PMID- 26370171 TI - Effect of microalgal treatments on pesticides in water. AB - The effect of the microalgae Chlorella vulgaris on a wide range of different pesticides in water was studied. Treatments included short-term exposure (1 h) to living and dead microalgal biomass and long-term exposure (4 days) to actively growing microalgae. The initial pesticide concentration was 63.5 +/- 3.9 ug L( 1). There was no significant overall reduction of pesticides after short-term exposure. A significant reduction of the total amount of pesticides was achieved after the long-term exposure to growing microalgae (final concentration 29.7 +/- 1.0 ug L(-1)) compared with the long-term control (37.0 +/- 1.2 ug L(-1)). The concentrations of 10 pesticides out of 38 tested were significantly lowered in the long-term algal treatment. A high impact of abiotic factors such as sunlight and aeration for pesticide reduction was observed when the initial control (63.5 +/- 3.9 ug L(-1)) and the long-term control (37.0 +/- 1.2 ug L(-1)) were compared. The results suggest that water treatment using microalgae, natural inhabitants of polluted surface waters, could be further explored not only for removal of inorganic nutrients but also for removal of organic pollutants in water. PMID- 26370172 TI - Structural and computational analysis of peptide recognition mechanism of class-C type penicillin binding protein, alkaline D-peptidase from Bacillus cereus DF4-B. AB - Alkaline D-peptidase from Bacillus cereus DF4-B, called ADP, is a D stereospecific endopeptidase reacting with oligopeptides containing D phenylalanine (D-Phe) at N-terminal penultimate residue. ADP has attracted increasing attention because it is useful as a catalyst for synthesis of D-Phe oligopeptides or, with the help of substrate mimetics, L-amino acid peptides and proteins. Structure and functional analysis of ADP is expected to elucidate molecular mechanism of ADP. In this study, the crystal structure of ADP (apo) form was determined at 2.1 A resolution. The fold of ADP is similar to that of the class C penicillin-binding proteins of type-AmpH. Docking simulations and fragment molecular orbital analyses of two peptides, (D-Phe)4 and (D-Phe)2-(L Phe)2, with the putative substrate binding sites of ADP indicated that the P1 residue of the peptide interacts with hydrophobic residues at the S1 site of ADP. Furthermore, molecular dynamics simulation of ADP for 50 nsec suggested that the ADP forms large cavity at the active site. Formation of the cavity suggested that the ADP has open state in the solution. For the ADP, having the open state is convenient to bind the peptides having bulky side chain, such as (D-Phe)4. Taken together, we predicted peptide recognition mechanism of ADP. PMID- 26370173 TI - Stathmin is enriched in the developing corticospinal tract. AB - Understanding the intra- and extracellular proteins involved in the development of the corticospinal tract (CST) may offer insights into how the pathway could be regenerated following traumatic spinal cord injury. Currently, however, little is known about the proteome of the developing corticospinal system. The present study, therefore, has used quantitative proteomics and bioinformatics to detail the protein profile of the rat CST during its formation in the spinal cord. This analysis identified increased expression of 65 proteins during the early ingrowth of corticospinal axons into the spinal cord, and 36 proteins at the period of heightened CST growth. A majority of these proteins were involved in cellular assembly and organization, with annotations being most highly associated with cytoskeletal organization, microtubule dynamics, neurite outgrowth, and the formation, polymerization and quantity of microtubules. In addition, 22 proteins were more highly expressed within the developing CST in comparison to other developing white matter tracts of the spinal cord of age-matched animals. Of these differentially expressed proteins, only one, stathmin 1 (a protein known to be involved in microtubule dynamics), was both highly enriched in the developing CST and relatively sparse in other developing descending and ascending spinal tracts. Immunohistochemical analyses of the developing rat spinal cord and fetal human brain stem confirmed the enriched pattern of stathmin expression along the developing CST, and in vitro growth assays of rat corticospinal neurons showed a reduced length of neurite processes in response to pharmacological perturbation of stathmin activity. Combined, these findings suggest that stathmin activity may modulate axonal growth during development of the corticospinal projection, and reinforces the notion that microtubule dynamics could play an important role in the generation and regeneration of the CST. PMID- 26370174 TI - Correction: Structure, function, self-assembly, and applications of bottlebrush copolymers. AB - Correction for 'Structure, function, self-assembly, and applications of bottlebrush copolymers' by Rafael Verduzco et al., Chem. Soc. Rev., 2015, 44, 2405-2420. PMID- 26370175 TI - Cathelicidin Antimicrobial Peptide: A Novel Regulator of Islet Function, Islet Regeneration, and Selected Gut Bacteria. AB - Cathelicidin antimicrobial peptide (CAMP) is a naturally occurring secreted peptide that is expressed in several organs with pleiotropic roles in immunomodulation, wound healing, and cell growth. We previously demonstrated that gut Camp expression is upregulated when type 1 diabetes-prone rats are protected from diabetes development. Unexpectedly, we have also identified novel CAMP expression in the pancreatic beta-cells of rats, mice, and humans. CAMP was present even in sterile rat embryo islets, germ-free adult rat islets, and neogenic tubular complexes. Camp gene expression was downregulated in young BBdp rat islets before the onset of insulitis compared with control BBc rats. CAMP treatment of dispersed islets resulted in a significant increase in intracellular calcium mobilization, an effect that was both delayed and blunted in the absence of extracellular calcium. Additionally, CAMP treatment promoted insulin and glucagon secretion from isolated rat islets. Thus, CAMP is a promoter of islet paracrine signaling that enhances islet function and glucoregulation. Finally, daily treatment with the CAMP/LL-37 peptide in vivo in BBdp rats resulted in enhanced beta-cell neogenesis and upregulation of potentially beneficial gut microbes. In particular, CAMP/LL-37 treatment shifted the abundance of specific bacterial populations, mitigating the gut dysbiosis observed in the BBdp rat. Taken together, these findings indicate a novel functional role for CAMP/LL-37 in islet biology and modification of gut microbiota. PMID- 26370176 TI - Characterization of the humoral and in situ autoantibody profile of scalp involvement in pemphigus. PMID- 26370178 TI - Developing five-membered heterocycle substituted phosphinous acids as ligands for palladium-catalyzed Suzuki-Miyaura and Catellani reactions. AB - A new category of secondary phosphine oxides (SPOs) (5a-5j) with/without benzo fused five-membered heterocyclic substituents were prepared. These new compounds are air- and moisture-stable ligands and have the advantage of long-term storage. Some of the ligands as well as ligand coordinated palladium complexes (6f' and 6f'') and platinum complexes (7b_trans & 7i_trans) were prepared and their structures were determined using single crystal X-ray diffraction methods. The crystal structure of 6f' revealed the formation of diamond shape di-palladium complexes with a Pd2Cl2 core. As for the structures of 7b_trans & 7i_trans, the processes for the generation of the trans-form of the bis-phosphine ligand coordinated platinum complexes are shown. These SPOs exhibit notable efficiencies in palladium-catalyzed Suzuki-Miyaura reactions. Moreover, organic compounds (9k and 10c) with unexpected conformations were obtained from Heck-type Catellani reactions. Reaction pathways are proposed to accommodate the probable routes for the formation of all organic products. PMID- 26370177 TI - Molecular Mechanism of Switching of TrkA/p75(NTR) Signaling in Monocrotophos Induced Neurotoxicity. AB - We demonstrate the role of molecular switching of TrkA/p75(NTR) signaling cascade in organophosphate pesticide-Monocrotophos (MCP) induced neurotoxicity in stem cell derived cholinergic neurons and in rat brain. Our in-silico studies reveal that MCP followed the similar pattern of binding as staurosporine and AG-879 (known inhibitors of TrkA) with TrkA protein (PDB ID: 4AOJ) at the ATP binding sites. This binding of MCP to TrkA led to the conformational change in this protein and triggers the cell death cascades. The in-silico findings are validated by observing the down regulated levels of phosphorylated TrkA and its downstream molecules viz., pERK1/2, pAkt and pCREB in MCP-exposed cells. We observe that these MCP induced alterations in pTrkA and downstream signaling molecules are found to be associated with apoptosis and injury to neurons. The down-regulation of TrkA could be linked to increased p75(NTR). The in-vitro studies could be correlated in the rat model. The switching of TrkA/p75(NTR) signaling plays a central role in MCP-induced neural injury in rBNSCs and behavioral changes in exposed rats. Our studies significantly advance the understanding of the switching of TrkA/p75(NTR) that may pave the way for the application of TrkA inducer/p75(NTR) inhibitor for potential therapeutic intervention in various neurodegenerative disorders. PMID- 26370179 TI - Covalency of hydrogen bonds in liquid water can be probed by proton nuclear magnetic resonance experiments. AB - The concept of covalency is widely used to describe the nature of intermolecular bonds, to explain their spectroscopic features and to rationalize their chemical behaviour. Unfortunately, the degree of covalency of an intermolecular bond cannot be directly measured in an experiment. Here we established a simple quantitative relationship between the calculated covalency of hydrogen bonds in liquid water and the anisotropy of the proton magnetic shielding tensor that can be measured experimentally. This relationship enabled us to quantify the degree of covalency of hydrogen bonds in liquid water using the experimentally measured anisotropy. We estimated that the amount of electron density transferred between molecules is on the order of 10 m while the stabilization energy due to this charge transfer is ~15 kJ mol(-1). The physical insight into the fundamental nature of hydrogen bonding provided in this work will facilitate new studies of intermolecular bonding in a variety of molecular systems. PMID- 26370180 TI - Fibroblast levels are increased in chronic rhinosinusitis with nasal polyps and are associated with worse subjective disease severity. AB - BACKGROUND: Fibroblasts are implicated in tissue remodeling and recruitment of inflammatory cells in chronic rhinosinusitis (CRS). Populations of fibroblasts remain unquantified in CRS subtypes. The objectives of this study were to measure fibroblast populations in subtypes of CRS, and to investigate the association between fibroblasts and disease severity. METHODS: Patients undergoing endoscopic sinus surgery (ESS) for CRS were prospectively enrolled from January 2011 to December 2014. Control subjects included patients undergoing endoscopic surgery for non-inflammatory conditions such as cerebrospinal fluid leak repair or non hormone-secreting pituitary tumors. Patients completed 22-item Sino-Nasal Outcome Test (SNOT-22) questionnaires prior to surgery. Blood and tissue biopsies were taken during surgery. Percent of sinonasal fibroblasts was determined via flow cytometry by selecting fibroblast-specific protein (FSP)-positive and Mucin 1 (MUC1)-negative cells. RESULTS: A total of 69 patients were enrolled: control (n = 24), CRS without nasal polyps (CRSsNP) (n = 13), CRS with nasal polyps (CRSwNP) (n = 22), and allergic fungal rhinosinusitis (AFRS) (n = 10). Patients with CRSwNP had significantly more fibroblasts than both control (p < 0.001) and CRSsNP (p < 0.01). Patients with AFRS had the most fibroblasts when compared to control (p < 0.0001), CRSsNP (p < 0.0001), and CRSwNP (p < 0.05). Atopy and asthma were not associated with increased fibroblasts in CRSwNP (p = 0.21, p = 0.26, respectively). Increased fibroblasts correlated with subjective disease severity as measured by SNOT-22 for CRSwNP (p = 0.003) and AFRS (p = 0.048). CONCLUSION: Sinonasal fibroblasts are increased in CRSwNP and AFRS compared to control and CRSsNP. Increased fibroblasts correlated with worse quality of life in CRSwNP and AFRS. PMID- 26370182 TI - Multidimensional MnO2 nanohair-decorated hybrid multichannel carbon nanofiber as an electrode material for high-performance supercapacitors. AB - One-dimensional (1D)-structured nanomaterials represent one of the most attractive candidates for energy-storage systems due to their contribution to design simplicity, fast charge-transportation network, and their allowance for more accessible ion diffusion. In particular, 1D-structured nanomaterials with a highly complex inner-pore configuration enhance functionality by taking advantage of both the hollow and 1D structures. In this study, we report a MnO2 nanohair decorated, hybrid multichannel carbon nanofiber (Mn_MCNF) fabricated via single nozzle co-electrospinning of two immiscible polymer solutions, followed by carbonization and redox reactions. With improved ion accessibility, the optimized Mn_MCNF sample (Mn_MCNF_60 corresponding to a reaction duration time of 60 min for optimal MnO2 nanohair growth) exhibited a high specific capacitance of 855 F g(-1) and excellent cycling performance with ~87.3% capacitance retention over 5000 cycles. PMID- 26370181 TI - Association between CCDC132, FDX1 and TNFSF13 gene polymorphisms and the risk of IgA nephropathy. AB - AIM: Previous genome-wide association studies have identified multiple susceptibility loci for IgA nephropathy (IgAN); however, validation of these findings is still needed. METHODS: We performed a case-control study among 347 Chinese Han IgAN patients and 310 ethnicity-matched controls. Twenty-two single nucleotide polymorphisms (SNPs) were genotyped and association analysis was performed. RESULTS: We found three alleles for IgAN in patients: the allele "C" of rs2188404 in the CCDC132 gene by recessive model (odds ratio (OR), 1.65; 95% confidence interval (CI), 1.10-2.48; P = 0.014) and additive model (OR, 1.29; 95% CI, 1.03-1.61; P = 0.024) analysis, respectively, the allele "A" of rs10488764 in FDX1 gene by additive model (OR, 1.27; 95% CI, 1.00-1.61; P = 0.048) analysis, the allele "A" of rs3803800 in TNFSF13 gene by recessive model (OR, 2.05; 95% CI, 1.16-3.62; P = 0.010) and additive model (OR, 1.35; 95% CI, 1.06-1.72; P = 0.013) analysis, respectively. However, the associations between these SNPs and the risk of IgAN were not significant when adjusted for age and sex. Additionally, we found polymorphisms of rs2188404, rs10488764 and rs3803800 were correlated with urine protein (UPRO), human serum albumin (HSA), total cholesterol (TC) and Lee's pathological grades. CONCLUSION: We did not find any positive association between these SNPs and the risk of IgAN after adjustment by age and sex, but did find a significant and strong correlation with relevant clinical pathological parameters. Our study may provide a new perspective to understanding the aetiology of IgAN. PMID- 26370183 TI - Suboptimal Dosing Parameters as Possible Factors in the Negative Phase III Clinical Trials of Progesterone for Traumatic Brain Injury. AB - To date, outcomes for all Phase III clinical trials for traumatic brain injury (TBI) have been negative. The recent disappointing results of the Progesterone for the Treatment of Traumatic Brain Injury (ProTECT) and Study of a Neuroprotective Agent, Progesterone, in Severe Traumatic Brain Injury (SyNAPSe) Phase III trials for progesterone in TBI have triggered considerable speculation about the reasons for the negative outcomes of these two studies in particular and for those of all previous Phase III TBI clinical trials in general. Among the factors proposed to explain the ProTECT III and SyNAPSe results, the investigators themselves and others have cited: 1) the pathophysiological complexity of TBI itself; 2) issues with the quality and clinical relevance of the preclinical animal models; 3) insufficiently sensitive clinical endpoints; and 4) inappropriate clinical trial designs and strategies. This paper highlights three critical trial design factors that may have contributed substantially to the negative outcomes: 1) suboptimal doses and treatment durations in the Phase II studies; 2) the strategic decision not to perform Phase IIB studies to optimize these variables before initiating Phase III; and 3) the lack of incorporation of the preclinical and Chinese Phase II results, as well as allometric scaling principles, into the Phase III designs. Given these circumstances and the exceptional pleiotropic potential of progesterone as a TBI (and stroke) therapeutic, we are advocating a return to Phase IIB testing. We advocate the incorporation of dose and schedule optimization focused on lower doses and a longer duration of treatment, combined with the addressing of other potential trial design problems raised by the authors in the recently published trial results. PMID- 26370184 TI - A patient with Alzheimer's disease complicated by elderly-onset Cushing's syndrome who had undergone surgical treatment for adrenocorticotropic hormone independent macronodular adrenal hyperplasia. AB - Cushing's syndrome (CS) is a rare disorder, especially in older people. Loss of brain volume and neurocognitive impairment of varying degrees has been demonstrated in patients with CS. However, there is a large difference between the median age of presentation of CS and that of Alzheimer's disease. We herein report a case of a patient with Alzheimer's disease complicated by elderly-onset CS who had undergone surgical treatment for adrenal hyperplasia. Surgical correction of hypercortisolism seems to have slowed the progression of brain volume loss and cognitive dysfunction and improved psychiatric symptoms such as visual hallucination, restlessness, and psychomotor excitement. These improvements have remarkably reduced the burden on the patient's caregivers. The present case suggests that subclinical CS may be present, particularly in rapidly progressive dementia, and that surgical treatment of CS for neuropsychiatric symptoms is useful. PMID- 26370185 TI - Impact of single-dose nandrolone decanoate on gonadotropins, blood lipids and HMG CoA reductase in healthy men. AB - The aim was to study the effect and time profile of a single dose of nandrolone decanoate (ND) on gonadotropins, blood lipids and HMG CoA reductase [3-hydroxy-3 methyl-glutaryl-CoA reductase (HMGCR)] in healthy men. Eleven healthy male participants aged 29-46 years were given a single dose of 150 mg ND as an intramuscular dose of Deca Durabol(r), Organon. Blood samples for sex hormones, lipids and HMGCR mRNA analysis were collected prior to ND administration day 0, 4 and 14. A significant suppression of luteinising hormone (LH) and follicle stimulating hormone (FSH) was seen after 4 days. Total testosterone and bioavailable testosterone level decreased significantly throughout the observed study period. A small but significant decrease in sexual hormone-binding globulin (SHBG) was seen after 4 days but not after 14 days. Total serum (S)-cholesterol and plasma (P)-apolipoprotein B (ApoB) increased significantly after 14 days. In 80% of the individuals, the HMGCR mRNA level was increased 4 days after the ND administration. Our results show that a single dose of 150 mg ND increases (1) HMGCR mRNA expression, (2) total S-cholesterol and (3) P-ApoB level. The long term consequences on cardiovascular risk that may appear in users remain to be elucidated. PMID- 26370186 TI - Antifouling activity of enzyme-functionalized silica nanobeads. AB - The amelioration of biofouling in industrial processing equipment is critical for performance and reliability. While conventional biocides are effective in biofouling control, they are potentially hazardous to the environment and in some cases corrosive to materials. Enzymatic approaches have been shown to be effective and can overcome the disadvantages of traditional biocides, however they are typically uneconomic for routine biofouling control. The aim of this study was to design a robust and reusable enzyme-functionalized nano-bead system having biofilm dispersion properties. This work describes the biochemical covalent functionalization of silica-based nanobeads (hereafter referred to as Si NanoB) with Proteinase K (PK). Results showed that PK-functionalized Si-NanoB are effective in dispersing both protein-based model biofilms and structurally altering Pseudomonas fluorescens biofilms, with significant decreases in surface coverage and thickness of 30.1% and 38.85%, respectively, while increasing surface roughness by 19 % following 24 h treatments on bacterial biofilms. This study shows that enzyme-functionalized nanobeads may potentially be an environmentally friendly and cost effective alternative to pure enzyme and chemical treatments. PMID- 26370188 TI - WriteClick nonresponders: Waiting, waffling, or weasling? PMID- 26370189 TI - Multidisciplinary treatment of a giant craniofacial neurofibroma with intratumoral hemorrhage. PMID- 26370187 TI - Safety and tolerability of sorafenib in patients with radioiodine-refractory thyroid cancer. AB - Effective adverse event (AE) management is critical to maintaining patients on anticancer therapies. The DECISION trial was a multicenter, randomized, double blind, placebo-controlled, Phase 3 trial which investigated sorafenib for treatment of progressive, advanced, or metastatic radioactive iodine-refractory, differentiated thyroid carcinoma. Four hundred and seventeen adult patients were randomized (1:1) to receive oral sorafenib (400 mg, twice daily) or placebo, until progression, unacceptable toxicity, noncompliance, or withdrawal. Progression-free survival, the primary endpoint of DECISION, was reported previously. To elucidate the patterns and management of AEs in sorafenib-treated patients in the DECISION trial, this report describes detailed, by-treatment cycle analyses of the incidence, prevalence, and severity of hand-foot skin reaction (HFSR), rash/desquamation, hypertension, diarrhea, fatigue, weight loss, increased serum thyroid stimulating hormone, and hypocalcemia, as well as the interventions used to manage these AEs. By-cycle incidence of the above-selected AEs with sorafenib was generally highest in cycle 1 or 2 then decreased. AE prevalence generally increased over cycles 2-6 then stabilized or declined. Among these AEs, only weight loss tended to increase in severity (from grade 1 to 2) over time; severity of HFSR and rash/desquamation declined over time. AEs were mostly grade 1 or 2, and were generally managed with dose interruptions/reductions, and concomitant medications (e.g. antidiarrheals, antihypertensives, dermatologic preparations). Most dose interruptions/reductions occurred in early cycles. In conclusion, AEs with sorafenib in DECISION were typically grade 1 or 2, occurred early during the treatment course, and were manageable over time. PMID- 26370190 TI - Neonatal dentate nucleus T2 hyperintensity after in utero metronidazole exposure. PMID- 26370191 TI - Age of first exposure to football and later-life cognitive impairment in former NFL players. PMID- 26370192 TI - Meningeal inflammation in multiple sclerosis: The key to the origin of cortical lesions? PMID- 26370193 TI - Residency Training: Determinants of burnout of neurology trainees in Attica, Greece. AB - OBJECTIVE: The purpose of our cross-sectional study was to estimate the rate of burnout and identify its determinants among neurology residents in Attica, Greece. METHODS: In total, 131 placements for neurology training over 18 hospitals were available. All residents were approached and were asked to participate in the study by anonymously completing a questionnaire. Job demands and resources (JD-R) were examined via a 31-item questionnaire assessing 8 factors based on the JD-R model. Burnout was measured with the Maslach Burnout Inventory (MBI). The emotional exhaustion + 1 criterion was used to distinguish respondents with and without burnout. RESULTS: A total of 116 residents participated in the study (response rate 88.5%). In total, 18.1% of the participants were experiencing burnout. Multivariate analysis showed that each increased point in the total score of the factor regarding opportunities for professional development was associated with lowering the odds of burnout by 28.7%. CONCLUSIONS: Burnout among neurology residents is associated with decreased professional development. Educators and program directors need to identify those residents at high risk of burnout and design interventions to promote residents' resilience and mental health. PMID- 26370194 TI - Pearls & Oy-sters: An isolated cranial nerve 6 palsy as a presentation of polycythemia vera. PMID- 26370195 TI - The impact of the Tekay chromoviral elements on genome organisation and evolution of Anemone s.l. (Ranunculaceae). AB - We studied the highly abundant chromoviral Tekay clade in species from three sister genera - Anemone, Pulsatilla and Hepatica (Ranunculaceae). With this clade, we performed a concomitant survey of its phylogenetic diversity, chromosomal organisation and transcriptional activity in Anemone s.l. in order to investigate dynamics of the Tekay elements at a finer scale than previously achieved in this or any other flowering clade. The phylogenetic tree built from Tekay sequences conformed to expected evolutionary relationships of the species; exceptions being A. nemorosa and A. sylvestris, which appeared more closely related that expected, and we invoke hybridisation events to explain the observed topology. The separation of elements into six clusters could be explained by episodic bursts of activity since divergence from a common ancestor at different points in their respective evolutionary histories. In Anemone s.l. the Tekay elements do not have a preferential position on chromosomes, i.e. they can have a: (i) centromeric/pericentromeric position; (ii) interstitial position in DAPI positive AT-rich heterochromatic regions; can be (iii) dispersed throughout chromosomes; or even (iv) be absent from large heterochromatic blocks. Widespread transcriptional activity of the Tekay elements in Anemone s.l. taxa indicate that some copies of Tekay elements could still be active in this plant group, contributing to genome evolution and speciation within Anemone s.l. Identification of Tekay elements in Anemone s.l. provides valuable information for understanding how different localisation patterns might help to facilitate plant genome organisation in a structural and functional manner. PMID- 26370196 TI - Identifying avian sources of faecal contamination using sterol analysis. AB - Discrimination of the source of faecal pollution in water bodies is an important step in the assessment and mitigation of public health risk. One tool for faecal source tracking is the analysis of faecal sterols which are present in faeces of animals in a range of distinctive ratios. Published ratios are able to discriminate between human and herbivore mammal faecal inputs but are of less value for identifying pollution from wildfowl, which can be a common cause of elevated bacterial indicators in rivers and streams. In this study, the sterol profiles of 50 avian-derived faecal specimens (seagulls, ducks and chickens) were examined alongside those of 57 ruminant faeces and previously published sterol profiles of human wastewater, chicken effluent and animal meatwork effluent. Two novel sterol ratios were identified as specific to avian faecal scats, which, when incorporated into a decision tree with human and herbivore mammal indicative ratios, were able to identify sterols from avian-polluted waterways. For samples where the sterol profile was not consistent with herbivore mammal or human pollution, avian pollution is indicated when the ratio of 24-ethylcholestanol/(24 ethylcholestanol + 24-ethylcoprostanol + 24-ethylepicoprostanol) is >=0.4 (avian ratio 1) and the ratio of cholestanol/(cholestanol + coprostanol + epicoprostanol) is >=0.5 (avian ratio 2). When avian pollution is indicated, further confirmation by targeted PCR specific markers can be employed if greater confidence in the pollution source is required. A 66% concordance between sterol ratios and current avian PCR markers was achieved when 56 water samples from polluted waterways were analysed. PMID- 26370197 TI - Assessment of future variability in extreme precipitation and the potential effects on the wadi flow regime. AB - The objective of this study is to investigate how the magnitude and occurrence of extreme precipitation events are affected by climate change and to predict the subsequent impacts on the wadi flow regime in the Al-Khod catchment area, Muscat, Oman. The tank model, a lumped-parameter rainfall-runoff model, was used to simulate the wadi flow. Precipitation extremes and their potential future changes were predicted using six-member ensembles of general circulation models (GCMs) from the Coupled Model Intercomparison Project Phase 5 (CMIP5). Yearly maxima of the daily precipitation and wadi flow for varying return periods were compared for observed and projected data by fitting the generalized extreme value (GEV) distribution function. Flow duration curves (FDC) were developed and compared for the observed and projected wadi flows. The results indicate that extreme precipitation events consistently increase by the middle of the twenty-first century for all return periods (49-52%), but changes may become more profound by the end of the twenty-first century (81-101%). Consequently, the relative change in extreme wadi flow is greater than twofolds for all of the return periods in the late twenty-first century compared to the relative changes that occur in the mid-century period. Precipitation analysis further suggests that greater than 50% of the precipitation may be associated with extreme events in the future. The FDC analysis reveals that changes in low-to-moderate flows (Q60-Q90) may not be statistically significant, whereas increases in high flows (Q5) are statistically robust (20 and 25% for the mid- and late-century periods, respectively). PMID- 26370198 TI - Immature platelet fraction and high-on treatment platelet reactivity with ticagrelor in patients with acute coronary syndromes. AB - Residual high-on treatment platelet reactivity (HRPR) has been associated with a 2-9 fold increased risk of acute ischemic events in patients with acute coronary syndromes or coronary stenting. However, the mechanism of suboptimal platelet inhibition are still poorly understood. Aim of present study was to evaluate the role of the percentage of reticulated platelets on HRPR with ticagrelor. In patients treated with ASA (100-160 mg) and ticagrelor (90 mg twice a day) platelet reactivity and the reticulated platelets fraction (immature platelets fraction, IPF) were assessed at 30-90 days after acute coronary syndrome. Aggregation was assessed by multiple-electrode aggregometry. HRPR was defined as ADP test >417 AU*min. Our population is represented by 190 patients, divided according to tertiles values of IPF (<2.5; 2.5-3.99; >=4 %). Higher IPF was associated to a larger platelet volume and lower platelets count (p < 0.001), and inversely related with a history of previous coronary revascularization (p = 0.03). Twenty-one out of 190 (11.0 %) patients displayed HRPR. No difference in the levels of circulating IPF was found in patients with or without HRPR (p = 0.25), with no correlation between the rate of reticulated platelets and platelet reactivity at ADP test (r = -0.084, p = 0.26). In fact no association was observed between high levels of IPF and the occurrence of HRPR (adjusted OR[95 % CI] = 0.69[0.34-1,37], p = 0.28), even after correction for baseline differences. In patients treated with ticagrelor, the levels of circulating reticulated platelets assessed at 30-90 days post-ACS are not associated with platelet reactivity or the occurrence of HRPR. PMID- 26370199 TI - Measurement tools and antidotes for non-vitamin K oral anticoagulants. PMID- 26370200 TI - Risk factors for pulmonary embolism in patients preliminarily diagnosed with community-acquired pneumonia: a prospective cohort study. AB - D-dimer levels are increased in patients with acute pulmonary embolism (PE). However, D-dimer levels are also increased in patients with community-acquired pneumonia (CAP). The aim of this prospective cohort study was to examine the incidence and clinical features of patients preliminarily diagnosed with CAP and with increased D-dimer levels, and who finally were diagnosed with PE. Patients diagnosed with CAP and hospitalized in the Respiratory Department of the Tenth People's Hospital Affiliated to Tongji University between May 2011 and May 2013 were enrolled. D-dimer levels were measured routinely after admission. For patients with increased D-dimer levels, those suspected with PE underwent computed tomography pulmonary angiography (CTPA). A total of 2387 patients with CAP was included: 724 (30.3 %) had increased D-dimer levels (median of 0.91 mg/L). CTPA was performed for 139 of the 724 patients (median D-dimer levels of 1.99 mg/L). Among the 139 patients, 80 were diagnosed with PE, and 59 without PE; D-dimer levels were 2.83 and 1.41 mg/L, respectively (p < 0.05). Multivariate analysis showed that age, coronary heart disease, chronic obstructive pulmonary disease (COPD), lower limb varicosity, chest pain, shortness of breath, hemoptysis, fever, and increased levels of troponin I were independent risk factors for PE. Presentation of PE and CAP are similar. Nevertheless, these results indicated that for hospitalized patients with CAP and elevated D-dimer levels, PE should be considered for those >60 years; with CHD, COPD, or lower limb varicosity; with chest pain, shortness of breath, hemoptysis, increased troponin I, or low fever. PMID- 26370201 TI - Psychosocial Challenges in Solid Organ Transplantation. AB - Organ transplantation is often a life-saving surgery for individuals with end stage organ disease. However, for most types of solid organ transplant, the demand for organs outweighs the supply, resulting in the need to institute a waiting list for suitable patients who cannot immediately receive an organ. Individuals who need transplants must undergo an assessment process that includes medical, surgical, and psychosocial evaluations. The transplant psychosocial evaluation considers whether surgical candidates are able and willing to care for the transplanted organ for many years. The evaluation must also consider a number of psychosocial risk factors that can lead to complications, which may cause premature loss of the graft. Some of these risk factors include a history of poor medical adherence, psychopathology (including substance use disorders), poor social support, and cognitive dysfunction. This article briefly summarizes the assessment of each of these risk factors and how they can be mitigated to ensure the best outcomes for patients and their families. PMID- 26370202 TI - The Role of Stigma in Parental Help-Seeking for Perceived Child Behavior Problems in Urban, Low-Income African American Parents. AB - Significant numbers of children have diagnosable mental health problems, but only a small proportion of them receive appropriate services. Stigma has been associated with help-seeking for adult mental health problems and for Caucasian parents. The current study aims to understand factors, including stigma, associated with African American parents' help-seeking behavior related to perceived child behavior problems. Participants were a community sample of African American parents and/or legal guardians of children ages 3-8 years recruited from an urban primary care setting (N = 101). Variables included child behavior, stigma (self, friends/family, and public), object of stigma (parent or child), obstacles for engagement, intention to attend parenting classes, and demographics. Self-stigma was the strongest predictor of help-seeking among African American parents. The impact of self-stigma on parents' ratings of the likelihood of attending parenting classes increased when parents considered a situation in which their child's behavior was concerning to them. Findings support the need to consider parent stigma in the design of care models to ensure that children receive needed preventative and treatment services for behavioral/mental health problems in African American families. PMID- 26370203 TI - A Social Ecological Model of Syndemic Risk affecting Women with and At-Risk for HIV in Impoverished Urban Communities. AB - Syndemic risk is an ecological construct, defined by co-occurring interdependent socio-environmental, interpersonal and intrapersonal determinants. We posited syndemic risk to be a function of violence, substance use, perceived financial hardship, emotional distress and self-worth among women with and at-risk for HIV in an impoverished urban community. In order to better understand these interrelationships, we developed and validated a system dynamics (SD) model based upon peer-reviewed literature; secondary data analyses of a cohort dataset including women living with and at-risk of HIV in Bronx, NY (N = 620); and input from a Bronx-based community advisory board. Simulated model output revealed divergent levels and patterns of syndemic risk over time across different sample profiles. Outputs generated new insights about how to effectively explore multicomponent multi-level programs in order to strategically develop more effective services for this population. Specifically, the model indicated that effective multi-level interventions might bolster women's resilience by increasing self-worth, which may result in decreased perceived financial hardship and risk of violence. Overall, our stakeholder-informed model depicts how self worth may be a major driver of vulnerability and a meaningful addition to syndemic theory affecting this population. PMID- 26370204 TI - Lasers in esthetic treatment of gingival melanin hyperpigmentation: a review article. AB - The health and suitability of mouth components play an important role towards defining facial attractiveness. An important component of the oral cavity is the color of the gingival tissue. Gingival melanin hyperpigmentation is caused by several reasons and affects people across ethnicity, race, age, and both gender. Lasers are presently being used for gingival melanin depigmentation. In this article, we reviewed studies on laser parameters, duration of gingival healing, pain perception during and after the operation, scores used for the evaluation of gingival melanin hyperpigmentation, follow-up period, treatment results, and recurrence reports. We conclude that laser ablation for gingival depigmentation is one of the most pleasant, reliable, acceptable, and impressive techniques available for treating gingival melanin hyperpigmentation. PMID- 26370205 TI - Effect of Nd:YAG laser irradiation and fluoride application in the progression of dentin erosion in vitro. AB - Nd:YAG laser and its association with fluoride have been proposed as an option for the prevention of dental erosion. This study evaluated the progression of existing dentin erosive lesions after treatment with different Nd:YAG laser (1064 nm) protocols, associated or not with fluoride. Erosive lesions were created with 1 % citric acid for 10 min in human dentin specimens. They were randomly assigned into eight groups (n = 15): no treatment (control), 1-min application of 2 % sodium fluoride gel (NaF), Nd:YAG1 (Nd:YAG laser irradiation 0.5 W; 50 mJ; ~41.66 J/cm(2); 10 Hz; 40 s; in contact), Nd:YAG2 (0.7 W; 70 mJ; ~62.50 J/cm(2); 10 Hz; 40 s; in contact), Nd:YAG3 (1 W; 100 mJ; ~54,16 J/cm(2); 10 Hz; 40 s; 1 mm unfocused), NaF + Nd:YAG1, NaF + Nd:YAG2, and NaF + Nd:YAG3. After treatment, the specimens were submitted to a 5-day erosion-remineralization cycling model, 6*/day. Dentin surface loss (SL) was evaluated with optical profilometry after the formation of the initial lesion; after treatment; and after days 1, 3, and 5. Data were statistically analyzed (alpha = 0.05). Significant differences were observed among the groups in all testing times (p < 0.001), except after initial lesion formation. Loss of dentin surface was observed after irradiation with all Nd:YAG laser protocols (p < 0.05). The association fluoride and laser did not differ significantly from laser alone. NaF showed the lowest values of SL and Nd:YAG2 and NaF + Nd:YAG2, the highest. Within the limitations of an in vitro study, it was concluded that laser irradiation, according to the parameters used, was not an appropriated approach to prevent dentin erosion progression, even when it was associated with fluoride. PMID- 26370206 TI - Ebola Preparedness Planning and Collaboration by Two Health Systems in Wisconsin, September to December 2014. AB - We describe the collaborative approach used by 2 health systems in Wisconsin to plan and prepare for the threat of Ebola virus disease. This was a descriptive study of the preparedness planning, infection prevention, and collaboration with public health agencies undertaken by 2 health systems in Wisconsin between September and December 2014. The preparedness approach used by the 2 health systems relied successfully on their robust infrastructure for planning and infection prevention. In the setting of rapidly evolving guidance and unprecedented fear regarding Ebola, the 2 health systems enhanced their response through collaboration and coordination with each other and government public health agencies. Key lessons learned included the importance of a rigorous planning process, robust infection prevention practices, and coalitions between public and private health sectors. The potential threat of Ebola virus disease stimulated emergency preparedness in which acute care facilities played a leading role in the public health response. Leveraging the existing expertise of health systems is essential when faced with emerging infectious diseases. (Disaster Med Public Health Preparedness. 2016;10:691-697). PMID- 26370207 TI - Challenges in the Diagnosis and Treatment of Homozygous Familial Hypercholesterolemia. AB - Homozygous familial hypercholesterolemia (HoFH) is a rare, genetic disorder characterized by an absence or impairment of low-density lipoprotein receptor (LDLR) function resulting in significantly elevated low-density lipoprotein cholesterol (LDL-C) levels. The cholesterol exposure burden beginning in utero greatly increases the risk for atherosclerotic cardiovascular disease (ASCVD) and premature death. The genetic heterogeneity of HoFH results in a wide range of LDL C levels among both untreated and treated patients. Diagnosis of HoFH should, therefore, be based on a comprehensive evaluation of clinical criteria and not exclusively LDL-C levels. As treatment goals, the European Atherosclerosis Society and International FH Foundation suggest target LDL-C levels of <100 mg/dL (<2.5 mmol/L) in adults or <70 mg/dL (<1.8 mmol/L) in adults with clinical coronary artery disease or diabetes. The National Lipid Association (NLA) recommends that LDL-C levels be reduced to <100 mg/dL (<2.5 mmol/L) or by at least >=50 % from pretreatment levels. Conventional therapy combinations that lower atherogenic lipoproteins levels in the blood, such as statins, ezetimibe, bile acid sequestrants and niacin, as well as lipoprotein apheresis, are usually unable to reduce LDL-C levels to recommended targets. Two recently approved agents that reduce lipoprotein synthesis and secretion by the liver are lomitapide, a microsomal triglyceride transfer protein inhibitor, and mipomersen, an apolipoprotein B antisense oligonucleotide. The newly approved inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9), evolocumab, also shows promise for the management of FH. Because of the extremely high risk for ASCVD, HoFH patients should be identified early. PMID- 26370208 TI - Direct Oral Anticoagulants for the Prevention of Stroke in Patients with Nonvalvular Atrial Fibrillation: Understanding Differences and Similarities. AB - The presence of atrial fibrillation (AF), the most common sustained cardiac arrhythmia, significantly increases the risk for stroke. Current guidelines recommend that the vitamin K antagonist warfarin or direct oral anticoagulants (DOACs), such as the approved direct thrombin inhibitor dabigatran and the approved direct factor Xa inhibitors apixaban, rivaroxaban, and edoxaban, should be used for thromboprophylaxis in patients with nonvalvular AF at risk for stroke or systemic embolic events (SEE). Warfarin, the mainstay of stroke prevention in AF, increases the risk of major bleeding. Furthermore, warfarin therapy comes with several limitations including frequent monitoring and the need for dose adjustments, unpredictable pharmacokinetics and pharmacodynamics, and the potential for significant drug-drug and food-drug interactions. The DOACs were developed to overcome these limitations while maintaining or surpassing warfarin's efficacy and safety profiles. All four DOACs have similar or better efficacy and safety compared with warfarin and are therefore valuable alternatives for the prevention of stroke and SEE in patients with nonvalvular AF. Understanding the subtle differences in the DOACs' pharmacology, phase 3 study designs, and trial outcomes will allow for a more tailored approach in selecting the right oral anticoagulant for each patient. PMID- 26370209 TI - Perampanel: A Review in Drug-Resistant Epilepsy. AB - Perampanel (Fycompa(r)), an orally-active, selective, noncompetitive alpha-amino 3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist, is a first-in-class antiepileptic drug (AED) offering the convenience of once-daily administration. In the EU and US, perampanel is approved in patients with epilepsy aged >=12 years for the adjunctive treatment of primary generalized tonic-clonic seizures (GTCS) and partial-onset seizures (POS; with or without secondary generalization). In phase III trials of 17 or 19 weeks' duration, add on perampanel <=12 mg/day significantly improved seizure control in patients aged >=12 years who were experiencing either primary GTCS or POS (with or without secondary generalization), despite ongoing treatment with stable dosages of one to three AEDs. Improvements in seizure control were maintained for up to 2 years in extensions of these core studies. Perampanel also provided sustained seizure control for up to ~4 years in an extension of two phase II studies in patients aged >=18 years with drug-resistant POS. Adjunctive perampanel therapy was generally well tolerated. Treatment-emergent adverse events were most commonly CNS-related (e.g. dizziness, somnolence, fatigue and irritability) and dose related; however, most were of mild to moderate intensity. Clinical experience with perampanel is accumulating, although comparative studies and pharmacoeconomic data that could assist in positioning it relative to other AEDS that are approved and/or recommended as adjunctive therapy are lacking. Nonetheless, on the basis of its overall clinical profile and unique mechanism of action, perampanel is a useful additional adjunctive treatment option for patients with drug-resistant POS, with or without secondary generalization, and primary GTCS. PMID- 26370210 TI - Alirocumab: First Global Approval. AB - Alirocumab (Praluent(r)) is a fully human monoclonal antibody developed by Regeneron Pharmaceuticals and Sanofi that has been approved in the US as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolaemia (HeFH) or clinical atherosclerotic cardiovascular disease, who require additional lowering of LDL-C. It specifically binds proprotein convertase subtilisin/kexin type 9 (PCSK9)-a down regulator of liver low-density lipoprotein (LDL)-receptors-thereby increasing the ability of the liver to bind LDL-cholesterol (LDL-C) and reducing levels of LDL-C in blood. It has been shown to reduce LDL-C levels in patients with hypercholesterolaemia, including HeFH, both as monotherapy and in conjunction with statin therapy. This article summarizes the milestones in the development of alirocumab leading to this first approval. PMID- 26370211 TI - Conformational Preferences of pi-pi Stacking Between Ligand and Protein, Analysis Derived from Crystal Structure Data Geometric Preference of pi-pi Interaction. AB - pi-pi Interaction is a direct attractive non-covalent interaction between aromatic moieties, playing an important role in DNA stabilization, drug intercalation, etc. Aromatic rings interact through several different conformations including face-to-face, T-shaped, and offset stacked conformation. Previous quantum calculations indicated that T-shaped and offset stacked conformations are preferred for their smaller electron repulsions. However, substitution group on aromatic ring could have a great impact on pi-pi interaction by changing electron repulsion force between two rings. To investigate pi-pi interaction between ligand and aromatic side chain of protein, Brookhaven Protein Data Bank was analyzed. We extracted isolated dimer pairs with the aim of excluding multiple pi-pi stacking effects and found that T-shaped conformation is prevalent among aromatic interaction between phenyl ring of ligand and protein, which corresponds with the phenomenon of Phe-Phe interactions in small peptide. Specifically, for the non-substitution model, both Phe-Phe and Phenyl-Phe exhibit a favored T-shaped conformation whose dihedral angle is around 50 degrees -70 degrees and centroid distance is between 5.0 and 5.6 A. However, it could be changed by substituent effect. The hydroxyl group could contact in the case of Tyr-Tyr pairs, while they point away from phenyl plane in Phe-Tyr pairs. PMID- 26370212 TI - Economic inequality is related to cross-national prevalence of psychotic symptoms. AB - PURPOSE: A burgeoning literature documents robust links of income inequality with the prevalence of psychological disorders. The aim of this paper is to extend this literature by examining the effects of cross-national income inequality on prevalence of psychotic symptoms. METHOD: Analyses used archival data of representative samples from 50 countries (N = 249,217). Four types of psychotic symptoms were assessed using the well-validated CIDI interview. We examined the effects of Standardized World Income Inequality Database (SWIID) measures of the concentration of income in the top percentile of people and the Gini coefficient of income inequality. RESULTS: Income inequality was significantly correlated with the national prevalence of hallucinations, delusions of thought control, and delusional mood, and effects withstood control over national indices of per capita income and regime type. Findings were also robust to nonparametric bootstrapping. CONCLUSIONS: Although the cross-sectional design limits ability to claim causality, income inequality appears important for understanding psychotic symptoms. PMID- 26370213 TI - Determinants of resource needs and utilization among refugees over time. AB - PURPOSE: This study examined refugees' resource needs and utilization over time, investigated the relationships between pre-displacement/socio-demographic variables and resource needs and utilization, and explored the role of resource needs and utilization on psychiatric symptom trajectories. METHODS: Iraqi refugees to the United States (N = 298) were assessed upon arrival and at 1-year intervals for 2 years for socio-demographic variables and pre-displacement trauma experiences, their need for and utilization of 14 different resources, and PTSD and depressive symptoms. RESULTS: Although refugees reported reduction of some needs over time (e.g., need for cash assistance declined from 99 to 71 %), other needs remained high (e.g., 99 % of refugees reported a need for health care at the 2-year interview). Generally, the lowest needs were reported after 2 years, and the highest utilization occurred during the first year post-arrival. Pre displacement trauma exposure predicted high health care needs but not high health care utilization. Both high need for and use of health care predicted increasing PTSD and depressive symptoms. Specifically, increased use of psychological care across the three measurement waves predicted more PTSD and depression symptoms at the 2-year interview. CONCLUSIONS: Differences emerged between need for and actual use of resources, especially for highly trauma-exposed refugees. Resettlement agencies and assistance programs should consider the complex relationships between resource needs, resource utilization, and mental health during the early resettlement period. PMID- 26370214 TI - Evaluation of uptake, cytotoxicity and inflammatory effects in respiratory cells exposed to pristine and -OH and -COOH functionalized multi-wall carbon nanotubes. AB - Toxic effects were reported for pristine-multi-wall carbon nanotubes (p-MWCNTs) while the role of the functionalization on MWCNT-induced toxicity is not yet well defined. We evaluated on human alveolar (A549) epithelial cells and normal bronchial (BEAS-2B) cells exposed to p-MWCNTs, MWCNTs-OH and MWCNTs-COOH: uptake by TEM, cell viability by different assays, membrane damage by the LDH assay and cytokine release by ELISA. The aims of the present study were to: (i) confirm MWCNT cytotoxicity mechanisms hypothesized in our previous studies; (ii) identify the most reliable viability assay to screen MWCNT toxicity; and (iii) to test our model to clarify the role of functionalization on MWCNT-induced toxicity. In A549 cells, p-MWCNTs and MWCNTs-OH were localized free in the cytoplasm and inside vacuoles whereas MWCNTs-COOH were confined inside filled cytoplasmic vesicles. WST-1 and Trypan blue assays showed in A549 cells a similar slight viability reduction for all MWCNTs whereas in BEAS-2B cells WST1 showed a high viability reduction at the highest concentrations, particularly for MWCNTs-COOH. The MTT assay showed a false cytotoxicity as a result of MWCNTs-interference. Pristine and MWCNTs-COOH induced membrane damage, particularly in BEAS-2B cells. MWCNTs COOH induced interleukin-6 (IL-6) and IL-8 release in A549 cells whereas p-MWCNTs induced IL-8 release in BEAS-2B cells. MWCNTs intracellular localization in A549 cells confirms the toxicity mechanisms previously hypothesized, with p-MWCNTs disrupting the membrane and vesicle-confined MWCNTs-COOH inducing inflammation. WST-1 was more reliable than MTT to test MWCNT-toxicity. BEAS-2B cells were more susceptible then A549 cells, particularly to MWCNT-COOH cytotoxicity. Our results confirm the toxicity of p-MWCNTs and demonstrate, also for the two kinds of tested functionalized MWCNTs toxic effects with a different mechanism of action. PMID- 26370215 TI - Extensive Adhesions in Living Donor Liver Transplantation: A Retrospective Analysis. AB - BACKGROUND: Adhesions are abnormal fibrous bands of scar tissue between internal organs and tissues. With respect to recipient hepatectomy in living donor liver transplantation (LDLT), we defined extensive adhesions as adhesions in at least two separate locations that required more than 5 % of the total surgical time to lyse. We aimed to identify the etiology and consequences of this preventable burden. METHODS: A simple retrospective case-control study of all cases with extensive adhesions from August 2011 to September 2014 matched by age, sex, and diagnosis at surgery. RESULTS: A total of 380 cases were studied. Thirty-eight and five patients had extensive adhesions from surgical and non-surgical causes, respectively. The incidence and complications in pediatric patients were far less than in adults. In the adult group, the mean operative time was increased by 75 min (12.3 %) and blood loss by 2.5 L.The incidence of bowel perforation and biliary infections were increased in adults, while there was no significant difference in the rate of ascitic or wound infections. The 1-year survival was slightly less (92 %) than the control group (100 %). CONCLUSIONS: The most common cause of extensive adhesions at LDLT was prior liver resection. Extensive adhesions caused increased morbidity by increased blood loss, transfusion requirements, and increased cold ischemia time. There is also a higher risk of bowel perforation during enterolysis. The use of commercially available barrier techniques is advisable in adults at high risk of developing adhesions with a possibility of liver transplantation, such as liver resection for HCC. PMID- 26370216 TI - The letter height superiority illusion. AB - Letters are identified better when they are embedded within words rather than within pseudowords, a phenomenon known as the word superiority effect (Reicher in Journal of Experimental Psychology, 81, 275-280, 1969). This effect is, inter alia, accounted for by the interactive-activation model (McClelland & Rumelhart in Psychological Review, 88, 375-407, 1981) through feedback from word to letter nodes. In this study, we investigated whether overactivation of features could lead to perceptual bias, wherein letters would be perceived as being taller than pseudoletters, or words would be perceived as being taller than pseudowords. In two experiments, we investigated the effects of letter and lexical status on the perception of size. Participants who had to compare the heights of letters and pseudoletters, or of words and pseudowords, indeed perceived the former stimuli as being taller than the latter. Possible alternative interpretations of this height superiority effect for letters and words are discussed. PMID- 26370217 TI - Intuitive visualizations of pitch and loudness in speech. AB - Visualizing acoustic features of speech has proven helpful in speech therapy; however, it is as yet unclear how to create intuitive and fitting visualizations. To better understand the mappings from speech sound aspects to visual space, a large web-based experiment (n = 249) was performed to evaluate spatial parameters that may optimally represent pitch and loudness of speech. To this end, five novel animated visualizations were developed and presented in pairwise comparisons, together with a static visualization. Pitch and loudness of speech were each mapped onto either the vertical (y-axis) or the size (z-axis) dimension, or combined (with size indicating loudness and vertical position indicating pitch height) and visualized as an animation along the horizontal dimension (x-axis) over time. The results indicated that firstly, there is a general preference towards the use of the y-axis for both pitch and loudness, with pitch ranking higher than loudness in terms of fit. Secondly, the data suggest that representing both pitch and loudness combined in a single visualization is preferred over visualization in only one dimension. Finally, the z-axis, although not preferred, was evaluated as corresponding better to loudness than to pitch. This relation between sound and visual space has not been reported previously for speech sounds, and elaborates earlier findings on musical material. In addition to elucidating more general mappings between auditory and visual modalities, the findings provide us with a method of visualizing speech that may be helpful in clinical applications such as computerized speech therapy, or other feedback-based learning paradigms. PMID- 26370218 TI - Bisdemethoxycurcumin-induced S phase arrest through the inhibition of cyclin A and E and induction of apoptosis via endoplasmic reticulum stress and mitochondria-dependent pathways in human lung cancer NCI H460 cells. AB - Curcuminoids are the major natural phenolic compounds found in the rhizome of many Curcuma species. Curcuminoids consist of a mixture of curcumin, demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC). Although numerous studies have shown that curcumin induced cell apoptosis in many human cancer cells, however, mechanisms of BDMC-inhibited cell growth and -induced apoptosis in human lung cancer cells still remain unclear. Herein, we investigated the effect of BDMC on the cell death via the cell cycle arrest and induction of apoptosis in NCI H460 human lung cancer cells. Flow cytometry assay was used to measure viable cells, cell cycle distribution, the productions of reactive oxygen species (ROS) and Ca2+ , mitochondrial membrane potential (DeltaPsim ) and caspase-3, -8 and -9 activity. DNA damage and condension were assayed by Comet assay and DAPI staining, respectively. Western blotting was used to measure the changes of cell cycle and apoptosis associated protein expressions. Results indicated that BDMC significantly induced cell death through induced S phase arrest and induced apoptosis. Moreover, DMC induced DNA damage and condension, increased ROS and Ca2+ productions and decreased the levels of DeltaPsim and promoted activities caspase-3, -8, and -9. Western blotting results showed that BDMC inhibited Cdc25A, cyclin A and E for causing S phase arrest, furthermore, promoted the expression of AIF, Endo G and PARP and the levels of Fas ligand (Fas L) and Fas were also up-regulated. Results also indicated that BDMC increased ER stress associated protein expression such as GRP78, GADD153, IRE1alpha, IRE1beta, ATF-6alpha, ATF-6beta, and caspase-4. Taken together, we suggest that BDMC induced cell apoptosis through multiple signal pathways such as extrinsic, intrinsic and ES tress pathway. (c) 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1899-1908, 2016. PMID- 26370219 TI - Facilitators and barriers to the increased supervisory role of senior charge nurses: a qualitative study. AB - AIMS: To explore the experiences of senior charge nurses provided with 'increased supervisory hours'. BACKGROUND: Designated supervisory time is essential for senior charge nurses to provide effective clinical leadership. It is important to explore the impact arises of such an increase. METHODS: An online questionnaire collected exploratory data from senior charge nurses (n = 60). Semi-structured interviews gathered in-depth qualitative data (n = 12). Findings were analysed for common themes associated with implementation of the increased senior charge nurse supervisory role. RESULTS: The majority of senior charge nurses were unable to use their full allocation of supervisory time. They struggled to accomplish leadership goals because of managing staffing levels, increased workload, time constraints and limited support. Factors that facilitated the role included preparation and support, adequate staff capacity, effective leadership skills and availability of supervisory time. The senior charge nurses took pride in providing clinical leadership, promoting staff development and delivering patient care. Support, in terms of preparation, capacity building and ongoing mentoring, was a key factor for achieving senior charge nurse goals. CONCLUSION: Senior charge nurses should be supported to maximise supervisory time through the provision of an induction programme, formal coaching and ongoing training and development. IMPLICATIONS FOR NURSING MANAGEMENT: Preparation and support is essential for senior charge nurses to deliver enhanced clinical leadership through increased supervisory time. PMID- 26370220 TI - Sotatercept (ACE-011) for the treatment of chemotherapy-induced anemia in patients with metastatic breast cancer or advanced or metastatic solid tumors treated with platinum-based chemotherapeutic regimens: results from two phase 2 studies. AB - PURPOSE: Sotatercept may represent a novel approach to the treatment of chemotherapy-induced anemia (CIA). We report the results from two phase 2 randomized studies examining the use of sotatercept for the treatment of CIA in patients with metastatic cancer. METHODS: In study A011-08, patients with metastatic breast cancer were randomized to 2:2:2:1 to receive sotatercept 0.1, 0.3, or 0.5 mg/kg, or placebo, respectively, every 28 days. In study ACE-011-NSCL 001, patients with solid tumors treated with platinum-based chemotherapy received sotatercept 15 or 30 mg every 42 days. The primary endpoint for both studies was hematopoietic response, defined as a hemoglobin (Hb) increase of >=1 g/dL from baseline. RESULTS: Both studies were terminated early due to slow patient accrual. Among patients treated with sotatercept in the A011-08 and ACE-011-NSCL 001 studies, more patients achieved a mean Hb increase of >=1 g/dL in the combined sotatercept 0.3 mg/kg and 15 mg (66.7 %) group and sotatercept 0.5 mg/kg and 30 mg (38.9 %) group versus the sotatercept 0.1 mg/kg (0 %) group. No patients achieved a mean Hb increase of >=1 g/dL in the placebo group. The incidence of treatment-related adverse events (AEs) was low in both studies, and treatment discontinuations due to AEs were uncommon. CONCLUSIONS: Although both studies were terminated early, these results indicate that sotatercept is active and has an acceptable safety profile in the treatment of CIA. PMID- 26370221 TI - Lifestyles of cancer survivors attending an inpatient educational program-a cross sectional study. AB - PURPOSE: Cancer survivors have increased risk for adverse health effects, but the risk can be reduced by adopting a healthy lifestyle. Knowledge of lifestyle in terms of physical activity (PA), diet (intake of fruit and vegetables [F&V]) and smoking behaviors of cancer survivors enrolled in an inpatient educational program and identification of subgroups not meeting the lifestyle guidelines are needed to set up more targeted programs. METHODS: We invited 862 cancer survivors, >=18 years, diagnosed within the last 10 years and about to attend a 1 week educational program, to participate in this cross-sectional study. Sixty seven percent (n = 576) returned the questionnaire before the start of the program. PA, F&V intake (5-A-Day) and smoking behaviors were self-reported. Logistic regression analyses were used to identify the characteristics of those not meeting the guidelines. RESULTS: Sixty-three percent were women, median age was 60 years (range 28-83), 52 % had high education and median time since diagnosis was 12 months (range 2-119). Fifty-five percent did not meet the PA guidelines, 81 % did not meet the 5-A-Day guidelines and 12 % were current smokers. In multivariate analyses, age >=60 years and low education were associated with not meeting the PA guidelines, and male gender and low education were associated with not meeting the 5-A-Day guidelines. Living alone was associated with smoking. CONCLUSIONS: The majority of cancer survivors attending an educational program do not meet the public guidelines for PA and diet. Special attention should be given to those who are male, over age 60 years and with low education. PMID- 26370222 TI - Use of best-worst scaling to assess patient perceptions of treatments for refractory overactive bladder. AB - AIMS: Refractory overactive bladder (OAB) treatments, including sacral neuromodulation (SNM), onabotulinumtoxin A (OnabotA), and percutaneous tibial nerve stimulation (PTNS), differ considerably. Best-Worst Scaling (BWS) was used to assess patient preferences for these treatments. METHODS: A cross-sectional Web survey, based on findings from qualitative interviews with 23 OAB patients and 7 clinical experts, was conducted with idiopathic OAB patients in the US and UK. The BWS exercise involved prioritizing subsets of 13 attributes across 13 choice tasks, where patients identified the attribute they considered as best and as worst in each task. Attribute BWS scores, ranging from -1.0 (worst) to 1.0 (best) were calculated based on the rates that each attribute was chosen. Attitudes toward the attributes also were assessed via like/dislike Likert scales, and questions regarding the percentage likelihood (0-100%) of trying each treatment, based on standardized treatment descriptions. RESULTS: The sample included 245 patients (118 US, 127 UK); 79% female, mean age 50 +/- 7.8 years. All 13 attribute BWS scores were significantly positive or negative. "Lasting improvement" (0.82), "minimal side effects" (0.67), and "sends signals between bladder and brain" (0.35)' were rated most favorably, and "complications with implant" (-0.65), and "be willing to self-catheterize" (-0.53) were rated worst. All but one of the attribute BWS scores were significantly correlated with the respective like/dislike scores and the percentage likelihood estimates for trying one of the three treatments. CONCLUSION: BWS was successful in assessing the magnitude of patient preferences for key attributes associated with substantially different refractory OAB therapies. Neurourol. Urodynam. 35:1028-1033, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26370223 TI - Niacin therapy and the risk of new-onset diabetes: a meta-analysis of randomised controlled trials. AB - OBJECTIVE: Previous studies have suggested that niacin treatment raises glucose levels in patients with diabetes and may increase the risk of developing diabetes. We undertook a meta-analysis of published and unpublished data from randomised trials to confirm whether an association exists between niacin and new onset diabetes. METHODS: We searched Medline, EMBASE and the Cochrane Central Register of Controlled Trials, from 1975 to 2014, for randomised controlled trials of niacin primarily designed to assess its effects on cardiovascular endpoints and cardiovascular surrogate markers. We included trials with >=50 non diabetic participants and average follow-up of >=24 weeks. Published data were tabulated and unpublished data sought from investigators. We calculated risk ratios (RR) for new-onset diabetes with random-effects meta-analysis. Heterogeneity between trials was assessed using the I(2) statistic. RESULTS: In 11 trials with 26 340 non-diabetic participants, 1371 (725/13 121 assigned niacin; 646/13 219 assigned control) were diagnosed with diabetes during a weighted mean follow-up of 3.6 years. Niacin therapy was associated with a RR of 1.34 (95% CIs 1.21 to 1.49) for new-onset diabetes, with limited heterogeneity between trials (I(2)=0.0%, p=0.87). This equates to one additional case of diabetes per 43 (95% CI 30 to 70) initially non-diabetic individuals who are treated with niacin for 5 years. Results were consistent regardless of whether participants received background statin therapy (p for interaction=0.88) or combined therapy with laropiprant (p for interaction=0.52). CONCLUSIONS: Niacin therapy is associated with a moderately increased risk of developing diabetes regardless of background statin or combination laropiprant therapy. PMID- 26370224 TI - Bilayer technique and nano-filled coating increase success of approximal ART restorations: a randomized clinical trial. AB - BACKGROUND: The high-viscosity consistency of glass ionomer cement (GIC) may lead to its incorrect adaptation into the cavity and therefore to restoration failure. AIM: To compare two different insertion techniques for GIC in approximal atraumatic restorative treatment (ART) restorations and two different surface protection materials. DESIGN: Approximal caries lesion in primary molars from 208 schoolchildren was randomly assigned into four groups: G1, conventional GIC insertion protected with petroleum jelly (PJ); G2, bilayer technique protected with PJ; G3 conventional GIC insertion protected with nano-filled particles coating for GIC (NPC); G4, bilayer technique protected with NPC. Restorations were evaluated after 1, 6, 12, 18, 24, and 36 months. Kaplan-Meier survival analysis and log-rank test were performed. Cox regression analysis (alpha = 5%) was used to verify the influence of clinical factors. RESULTS: Restoration survival was 52.8%. Log-rank test indicated a better survival of the bilayer technique restorations, compared to conventional restorations (P = 0.005), whereas the coated conventional restorations presented higher survival than the uncoated ones (P = 0.035). Cox regression analysis showed no influence of any clinical tested variables. CONCLUSION: The survival rate of the approximal ART restorations is positively influenced by the bilayer technique, and the application of nano-filled coating increases the longevity of the conventional approximal ART restorations. PMID- 26370225 TI - Frequency of undiagnosed psoriatic arthritis among psoriasis patients in Australian dermatology practice. AB - BACKGROUND: Psoriatic arthritis commonly develops in psoriasis patients and, if undiagnosed, can lead to potentially avoidable joint damage and an increased risk of comorbidity and mortality. Increased awareness of PsA symptoms among dermatologists provides an opportunity for earlier diagnosis, more timely therapy and prevention of disability. OBJECTIVE: To provide Australian epidemiological data on the frequency of undiagnosed PsA among psoriasis patients in dermatology practice, and to investigate the impact of psoriasis on quality of life and work productivity. METHODS: Nine tertiary centre dermatology practices enrolled patients presenting with plaque psoriasis and no prior rheumatologist-confirmed PsA diagnosis. Patients were screened using the Psoriatic Arthritis Screening and Evaluation (PASE) questionnaire and were referred to a rheumatologist for assessment of PsA status using CASPAR criteria if they had a PASE score >=44. RESULTS: Based on the composite and sequential application of PASE and CASPAR criteria, undiagnosed PsA among psoriasis patients in this study is 9% [95% CI: 6, 12]. The PPV of PASE in this setting is 26% [95% CI: 19, 34]. Nail involvement and chronic large plaque psoriasis were identified as independent positive predictors of PsA, whereas scalp psoriasis was an independent negative predictor of PsA. Patients with moderate-to-severe psoriasis (PASI >=15) had lower quality of life scores than patients with less severe psoriasis. CONCLUSION: In this study, the frequency of undiagnosed PsA in Australian dermatology practice was 9% among plaque psoriasis patients with no prior PsA diagnosis. Compared with psoriasis alone, the impact of undiagnosed PsA on health-related quality of life of psoriasis patients is substantial. PMID- 26370226 TI - "Phylogenetic and evolutionary analysis of functional divergence among Gamma glutamyl transpeptidase (GGT) subfamilies". AB - BACKGROUND: gamma-glutamyltranspeptidase (GGT) is a bi-substrate enzyme conserved in all three domains of life. It catalyzes the cleavage and transfer of gamma glutamyl moiety of glutathione to either water (hydrolysis) or substrates like peptides (transpeptidation). GGTs exhibit great variability in their enzyme kinetics although the mechanism of catalysis is conserved. Recently, GGT has been shown to be a virulence factor in microbes like Helicobacter pylori and Bacillus anthracis. In mammalian cells also, GGT inhibition prior to chemotherapy has been shown to sensitize tumors to the therapy. Therefore, lately both bacterial and eukaryotic GGTs have emerged as potential drug targets, but the efforts directed towards finding suitable inhibitors have not yielded any significant results yet. We propose that delineating the residues responsible for the functional diversity associated with these proteins could help in design of species/clade specific inhibitors. RESULTS: In the present study, we have carried out phylogenetic analysis on a set of 47 GGT-like proteins to address the functional diversity. These proteins segregate into various subfamilies, forming separate clades on the tree. Sequence conservation and motif prediction studies show that even though most of the highly conserved residues have been characterized biochemically in previous studies, a significant number of novel putative sites and motifs are discovered that vary in a clade specific manner. Many of the putative sites predicted during the functional divergence type I and type II analysis, lie close to the known catalytic residues and line the walls of the substrate binding cavity, reinforcing their role in modulating the substrate specificity, catalytic rates and stability of this protein. CONCLUSION: The study offers interesting insights into the evolution of GGT-like proteins in pathogenic vs. non-pathogenic bacteria, archaea and eukaryotes. Our analysis delineates residues that are highly specific to each GGT subfamily. We propose that these sites not only explain the differences in stability and catalytic variability of various GGTs but can also aid in design of specific inhibitors against particular GGTs. Thus, apart from the commonly used in-silico inhibitor screening approaches, evolutionary analysis identifying the functional divergence hotspots in GGT proteins could augment the structure based drug design approaches. PMID- 26370227 TI - Comparative genomics between human and animal associated subspecies of the Mycobacterium avium complex: a basis for pathogenicity. AB - BACKGROUND: A human isolate of Mycobacterium avium subsp. paratuberculosis (M. paratuberculosis 43525) was sequenced and compared genomically to other mycobacterial pathogens. M. paratuberculosis 43525 was recently isolated from a patient with ulcerative colitis and belongs to the M. avium complex, a group known to infect both humans and animals. While M. paratuberculosis is a known pathogen of livestock, there are only 20 human isolates from the last 20 years, therefore we took the opportunity to perform a whole genome comparison between human and animal mycobacterial pathogens. We also compared virulence determinants such as the mycobactin cluster, PE/PPE genes and mammalian cell entry (mce) operons between MAC subspecies that infect animals and those that infect humans. M. tuberculosis was also included in these analyses given its predominant role as a human pathogen. RESULTS: This genome comparison showed the PE/PPE profile of M. paratuberculosis 43525 to be largely the same as other M. paratuberculosis isolates, except that it had one PPE and one PE_PGRS protein that are only present in human MAC strains and M. tuberculosis. PE/PPE proteins that were unique to M. paratuberculosis 43525, M. avium subsp. hominissuis and a caprine M. paratuberculosis isolate, were also identified. In addition, the mycobactin cluster differed between human and animal isolates and a unique mce operon flanked by two mycobactin genes, mbtA and mbtJ, was identified in all available M. paratuberculosis genomes. CONCLUSIONS: Despite the whole genome comparison placing M. paratuberculosis 43525 as closely related to bovine M. paratuberculosis, key virulence factors were similar to human mycobacterial pathogens. This study highlights key factors of mycobacterial pathogenesis in humans and forms the basis for future functional studies. PMID- 26370229 TI - Erratum to: Ectopic ACTH secretion associated to a well-differentiated peritoneal mesothelioma. PMID- 26370228 TI - Longitudinal analysis of immune abnormalities in varying severities of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis patients. AB - BACKGROUND: Research has identified immunological abnormalities in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME), a heterogeneous illness with an unknown cause and absence of diagnostic test. There have been no CFS/ME studies examining innate and adaptive immune cells longitudinally in patients with varying severities. This is the first study to investigate immune cells over 6 months while also examining CFS/ME patients of varying symptom severity. METHODS: Participants were grouped into 18 healthy controls, 12 moderate and 12 severe CFS/ME patients and flow cytometry was used to examine cell parameters at 0 and 6 months. RESULTS: Over time, iNKT CD62L expression significantly increased in moderate CFS/ME patients and CD56(bright) NK receptors differed in severe CFS/ME. Naive CD8(+)T cells, CD8(-)CD4(-) and CD56(-)CD16(-) iNKT phenotypes, gammadelta2T cells and effector memory subsets were significantly increased in severe CFS/ME patients at 6 months. Severe CFS/ME patients were significantly reduced in CD56(bright)CD16(dim) NKG2D, CD56(dim)CD16(-) KIR2DL2/DL3, CD94( )CD11a(-) gammadelta1T cells and CD62L(+)CD11a(-) gammadelta1T cells at 6 months. CONCLUSIONS: Severe CFS/ME patients differed from controls and moderate CFS/ME patients over time and expressed significant alterations in iNKT cell phenotypes, CD8(+)T cell markers, NK cell receptors and gammadeltaT cells at 6 months. This highlights the importance of further assessing these potential immune biomarkers longitudinally in both moderate and severe CFS/ME patients. PMID- 26370230 TI - Meta-analysis of locking plate versus intramedullary nail for treatment of proximal humeral fractures. AB - PURPOSE: This meta-analysis compared the clinical outcomes of locking plate with intramedullary nail in the treatment of displaced proximal humeral fractures. METHODS: We searched PubMed, Embase, and the Cochrane databases for studies comparing locking plate and intramedullary nail treatment of displaced two-, three-, or four-part proximal humeral fractures. The quality of the studies was assessed, and meta-analysis was performed using the Cochrane Collaboration's REVMAN 5.1 software. RESULTS: A total of 615 patients from eight studies were included in this meta-analysis (348 fractures treated with locking plate and 267 with intramedullary nail). Similar Constant scores were observed between the locking plate and intramedullary nail both in randomized controlled trials (RCTs) (mean difference (MD) = 2.12, 95% confidence interval (CI), -2.54 to 6.79, P = 0.37) and observational studies (MD = -1.93, 95% CI, -4.95 to 1.09, P = 0.21). Only one RCT provided American Shoulder and Elbow Surgeons Standardized scores indicating that the locking plate was better than the intramedullary nail (MD = 7.20, 95% CI, 1.29-13.11, P = 0.02). The total complication rate did not specifically favor the locking plate or intramedullary nail both in the RCTs (risk ratio (RR), 2.44; 95% CI, 0.35-16.78; P = 0.37) and observational studies (RR, 1.01; 95% CI, 0.72-1.43; P = 0.94). CONCLUSIONS: In the existing literature, limited evidence suggests that the locking plate and intramedullary nail are both valuable options for the treatment of proximal humeral fractures. Because of the observed heterogeneity and variance between the subgroups, more RCT are needed to be able to definitively recommend a locking plate or intramedullary nail for specific fracture patterns. PMID- 26370231 TI - A complete mitochondrial genome of the Damaraland mole rat Fukomys damarensis retrieved from the published genome of the brandt's bat Myotis brandtii. AB - We reported the complete mitochondrial genome of the Damaraland mole rat Fukomys damarensis which was retrieved from the published genome of the Brandt's bat Myotis brandtii. The mitogenome of F. damarensis is 16 868 bp in length with a base composition of 33.81% A, 30.79% T, 22.20% C, and 13.20% G, and contains 22 tRNA, two rRNA, 13 protein-coding genes, and a non-coding control region. The sequence of F. damarensis was verified by a phylogenetic analysis. Our study suggests a caution when utilizing the published genome assembly generated by next generation sequencing. PMID- 26370233 TI - Anti-NMDAR encephalitis after resection of melanocytic nevi: report of two cases. AB - BACKGROUND: Encephalitis with antibodies against N-methyl D-aspartate receptor (NMDAR) is recognized as a group of antibody-mediated neuropsychiatric syndromes, which occurs with and without a tumor association. Neoplasm may contribute to the pathogenesis of Anti-NMDAR encephalitis in tumor-positive patients. However, the underlying causes in tumor-negative patients are largely unknown. This is the first report, of which we are aware, of two cases of anti-NMDAR encephalitis after the resection of melanocytic nevus. CASE PRESENTATION: We describe 2 female patients in their 20s confirmed with anti-NMDAR encephalitis. They shared two points in common: About several weeks (2 weeks and 5 weeks respectively) before the initial symptom, both of them underwent a resection of melanocytic nevi; the screening tests for an ovarian teratoma and other tumors were all negative. A 25 year-old woman presented with seizure, psychiatric symptoms and behavioral change for 2 weeks. Electroencephalogram indicated electrographic seizures. Anti-NMDAR antibodies were all positive in the cerebrospinal fluid and serum. Her symptoms relieved gradually after the treatment with steroids and mycophenolate mofetil. Another patient admitted to our hospital with psychosis, behavioral change and complex partial seizure over a period of 5 months. Electroencephalogram demonstrated generalized slow activities. High titres of anti-NMDAR antibodies were both detected in the cerebrospinal fluid and serum. She responded well to the first-line immunotherapy and got substantial recovery. CONCLUSION: Our cases provided an observational link between anti-NMDAR encephalitis and resection of nevi. We postulate that the exposure of certain antigen on nevus cell caused by nevi excision, which might be NMDA receptor or other mimic cross-reactive antigens, may trigger an autoimmune response resulting in encephalitis. This suggested a potential site of antigen exposure triggering the immune response in non-tumor associated anti-NMDAR encephalitis, which may lend support to elucidating the underlying immunopathological mechanisms. Further studies are expected for investigating the expression of NMDA receptor on nevus cell and evaluating the validity of this hypothesis. PMID- 26370232 TI - Diversification of non-visual photopigment parapinopsin in spectral sensitivity for diverse pineal functions. AB - BACKGROUND: Recent genome projects of various animals have uncovered an unexpectedly large number of opsin genes, which encode protein moieties of photoreceptor molecules, in most animals. In visual systems, the biological meanings of this diversification are clear; multiple types of visual opsins with different spectral sensitivities are responsible for color vision. However, the significance of the diversification of non-visual opsins remains uncertain, in spite of the importance of understanding the molecular mechanism and evolution of varied non-visual photoreceptions. RESULTS: Here, we investigated the diversification of the pineal photopigment parapinopsin, which serves as the UV sensitive photopigment for the pineal wavelength discrimination in the lamprey, linking it with other pineal photoreception. Spectroscopic analyses of the recombinant pigments of the two teleost parapinopsins PP1 and PP2 revealed that PP1 is a UV-sensitive pigment, similar to lamprey parapinopsin, but PP2 is a blue sensitive pigment, with an absorption maximum at 460-480 nm, showing the diversification of non-visual pigment with respect to spectral sensitivity. We also found that PP1 and PP2 exhibit mutually exclusive expressions in the pineal organs of three teleost species. By using transgenic zebrafish in which these parapinopsin-expressing cells are labeled, we found that PP1-expressing cells basically possess neuronal processes, which is consistent with their involvement in wavelength discrimination. Interestingly, however, PP2-expressing cells rarely possess neuronal processes, raising the possibility that PP2 could be involved in non-neural responses rather than neural responses. Furthermore, we found that PP2 expressing cells contain serotonin and aanat2, the key enzyme involved in melatonin synthesis from serotonin, whereas PP1-expressing cells do not contain either, suggesting that blue-sensitive PP2 is instead involved in light regulation of melatonin secretion. CONCLUSIONS: In this paper, we have clearly shown the different molecular properties of duplicated non-visual opsins by demonstrating the diversification of parapinopsin with respect to spectral sensitivity. Moreover, we have shown a plausible link between the diversification and its physiological impact by discovering a strong candidate for the underlying pigment in light-regulated melatonin secretion in zebrafish; the diversification could generate a new contribution of parapinopsin to pineal photoreception. Current findings could also provide an opportunity to understand the "color" preference of non-visual photoreception. PMID- 26370234 TI - The relationship between the duration of obstructive respiratory events and outcomes of multilevel upper airway surgery in patients with obstructive sleep apnea. AB - We aimed to examine whether the duration of respiratory events and related oximetric values are associated with outcomes of multilevel upper airway surgery in patients with moderate-severe obstructive sleep apnea (OSA). The records of patients with a preoperative apnea-hypopnea index (AHI) >15 events/h, who underwent uvulopharyngopalatoplasty plus tongue base suspension with or without septoplasty between 2012 and 2014, were reviewed retrospectively. If the postoperative 6th month AHI was <20 events/h with at least a 50 % reduction from preoperative rates, the outcome of surgery was regarded as successful, otherwise, as failure. To calculate factors predictive of surgical outcomes, a receiver operating characteristic (ROC) analysis was performed. Logistic regression analyses were utilized to obtain the Odds ratio (OR) and 95 % confidential interval (CI). In total, 82 patients were enrolled in the study. Sixty-one patients (74.4 %) met the success criteria. The mean obstructive apnea duration (OAD) was the sole variable with a significant and satisfactory area under the curve (AUC) value [AUC (95 % CI) = 0.719 (0.597-0.842), p = 0.003]. The cutoff value was found to be 26.75 s with 71.4 % sensitivity, 72.1 % specificity, 88.0 % positive predictive value, and 46.9 % negative predictive value. Univariate analysis revealed an association between surgical failure and mean OAD > 26.75 s, total apnea duration, lowest SaO2, mean SaO2, mean O2 desaturation, and oxygen desaturation index, although only mean OAD > 26.75 s remained to be an independent predictor for unfavorable outcome after adjustment for other confounders in multivariate analysis [OR (95 % CI) = 3.92 (1.08-14.17), p = 0.041]. The current study suggests that OSA patients having longer OAD are in the risk of having surgical failure. PMID- 26370235 TI - Assessment of the effect of deviated nasal septum on the structure of nasal cavity. AB - The present study was aimed to investigate the effects of DNS on the structure of nasal cavity. The paranasal sinus coronal view CT of 108 patients with DNS and 129 hospitalized patients without DNS was retrospectively analyzed. The transverse diameter of nasal cavity (a), transverse diameter of nasal cavity and paranasal sinus (b), angle between maxillary and palatal bone, interalveolar distance, and maxillary rotation distance were measured. The ratio of a/b in experimental group was 0.367 +/- 0.006 which was significantly (P = 0.0023) less than that in control group (0.391 +/- 0.005). For the angle between maxillary and palatal bone, there was no significant difference found between DNS and control group for both right and left sides. The interalveolar distance was 40.75 mm in experimental group, and 38.8 mm in control (P = 0.0002). For the maxillary rotation distance, findings were considered as significant (P < 0.0001) in experimental group (11.25 mm) compared with control (10.1 mm). The present study demonstrates that long-term DNS affects the development of nasal cavity and paranasal sinus, as well as increases the interalveolar distance and maxillary rotation distance. These influences may be caused by the alteration of airflow inside the nasal cavities. PMID- 26370236 TI - Brain metastasis in children with stage 4 neuroblastoma after multidisciplinary treatment. AB - INTRODUCTION: Brain metastasis is common in relapsed neuroblastoma patients, but the characteristics of brain metastasis remain largely unknown. This study aimed to investigate the status of brain metastasis with neuroblastoma in South China. METHODS: In this retrospective case-based study, 106 patients with stage 4 neuroblastoma from the Department of Pediatric Oncology in Sun Yat-sen University Cancer Center between January 2004 and May 2013 were included. The incidence, risk factors, and survival status of these patients were reviewed and analyzed. RESULTS: Of the 106 patients, 11 (10.4%) developed brain metastasis, accounting for 20.0% of 55 patients with relapse or progression. The age at initial diagnosis of the 11 patients ranged from 2 to 10 years (median 4 years), which was younger than that of the patients without brain metastasis (median 5 years, range 1-10 years, P=0.073). The male to female ratio of the 11 patients was 8:3, which was not significantly different from that of the patients without brain metastasis (P=0.86). Patients with brain metastasis had higher lactate dehydrogenase levels than those without brain metastasis, but the differences were not significant (P=0.076). Eight patients died, and 3 patients survived. The median interval from the initial diagnosis to the development of brain metastasis was 18 months (range 6-32 months). The median survival was 4 months (range 1 day to 29 months) after the diagnosis of brain metastasis. The median interval from the manifestation of brain metastasis to death was 3 months (range 1 day to 11 months). CONCLUSIONS: High-risk factors for brain metastasis in cases of neuroblastoma include bone marrow involvement and a younger age at initial diagnosis. Nevertheless, multiple treatment modalities can improve disease-free survival. PMID- 26370237 TI - Use of attribute association error probability estimates to evaluate quality of medical record geocodes. AB - BACKGROUND: The utility of patient attributes associated with the spatiotemporal analysis of medical records lies not just in their values but also the strength of association between them. Estimating the extent to which a hierarchy of conditional probability exists between patient attribute associations such as patient identifying fields, patient and date of diagnosis, and patient and address at diagnosis is fundamental to estimating the strength of association between patient and geocode, and patient and enumeration area. We propose a hierarchy for the attribute associations within medical records that enable spatiotemporal relationships. We also present a set of metrics that store attribute association error probability (AAEP), to estimate error probability for all attribute associations upon which certainty in a patient geocode depends. METHODS: A series of experiments were undertaken to understand how error estimation could be operationalized within health data and what levels of AAEP in real data reveal themselves using these methods. Specifically, the goals of this evaluation were to (1) assess if the concept of our error assessment techniques could be implemented by a population-based cancer registry; (2) apply the techniques to real data from a large health data agency and characterize the observed levels of AAEP; and (3) demonstrate how detected AAEP might impact spatiotemporal health research. RESULTS: We present an evaluation of AAEP metrics generated for cancer cases in a North Carolina county. We show examples of how we estimated AAEP for selected attribute associations and circumstances. We demonstrate the distribution of AAEP in our case sample across attribute associations, and demonstrate ways in which disease registry specific operations influence the prevalence of AAEP estimates for specific attribute associations. CONCLUSIONS: The effort to detect and store estimates of AAEP is worthwhile because of the increase in confidence fostered by the attribute association level approach to the assessment of uncertainty in patient geocodes, relative to existing geocoding related uncertainty metrics. PMID- 26370238 TI - Disparities in type 2 diabetes prevalence among ethnic minority groups resident in Europe: a systematic review and meta-analysis. AB - Many ethnic minorities in Europe have a higher type 2 diabetes (T2D) prevalence than their host European populations. The risk size differs between ethnic groups, but the extent of the differences in the various ethnic minority groups has not yet been systematically quantified. We conducted a meta-analysis of published data on T2D in various ethnic minority populations resident in Europe compared to their host European populations. We systematically searched MEDLINE (using PUBMED) and EMBASE for papers on T2D prevalence in ethnic minorities in Europe published between 1994 and 2014. The ethnic minority groups were classified into five population groups by geographical origin: South Asian (SA), Sub-Saharan African (SSA), Middle Eastern and North African (MENA), South and Central American (SCA), and Western Pacific (WP). Pooled odds ratios with corresponding 95 % confidence interval (CI) were calculated using Review Manager 5.3. Twenty articles were included in the analysis. Compared with the host populations, SA origin populations had the highest odds for T2D (3.7, 95 % CI 2.7 5.1), followed by MENA (2.7, 95 % CI 1.8-3.9), SSA (2.6, 95 % CI 2.0-3.5), WP (2.3, 95 % CI 1.2-4.1), and lastly SCA (1.3, 95 % CI 1.1-1.6). Odds ratios were in all ethnic minority populations higher for women than for men except for SCA. Among SA subgroups, compared with Europeans, Bangladeshi had the highest odds ratio of 6.2 (95 % CI 3.9-9.8), followed by Pakistani (5.4, 95 % CI 3.2-9.3) and Indians (4.1, 95 % CI 3.0-5.7). The risk of T2D among ethnic minority groups living in Europe compared to Europeans varies by geographical origin of the group: three to five times higher among SA, two to four times higher among MENA, and two to three times higher among SSA origin. Future research and policy initiatives on T2D among ethnic minority groups should take the interethnic differences into account. PMID- 26370239 TI - Computed tomography perfusion-based thrombolysis in wake-up stroke. AB - Wake-up stroke (WUS) patients are typically excluded from reperfusion treatment, as the time of symptoms onset is unknown. The purpose of this study is to evaluate the clinical outcome and safety of intravenous thrombolysis with rt-PA in patients with WUS eligible for therapy using computed tomography perfusion criteria (CTP), compared to patients treated with rt-PA within 4.5 h of symptoms onset (non-WUS). This is an experimental, open-label trial, controlled against the best therapy currently in use. Primary endpoints were functional independence after 3 months [modified Rankin scale (mRS) <= 1] for clinical outcome and symptomatic intracerebral hemorrhage (SICH) for safety. Secondary endpoints were no or only mild disability after 3 months (mRS <= 2) for clinical outcome, total intracerebral hemorrhage (TICH) and contrast-induced nephropathy (CIN) for safety. 170 patients were treated, 143 non-WUS patients and 27 patients with WUS. Strokes of cardioembolic origin were most common in WUS patients (p < 0.001). Primary endpoints: mRS <= 1 was found in 35.8 % (non-WUS: 36.4% vs. WUS 33.3%; p = 0.62) and SICH was observed in 3.4 % of non-WUS patients and in WUS patients (p = 0.32). Secondary endpoints: mRS <= 2 was observed in 66.4 % of patients (non WUS: 67.1% vs. WUS 62.9%; p = 0.67), TICH in 13.5 % of patients (13.9 % non-WUS vs. 11.1 % WUS; p = 0.69). CIN was documented in 3.7 % of WUS patients. rt-PA treatment carried out in WUS patients selected on the basis of CTP data demonstrate comparable clinical outcome and safety with respect to non-WUS patients. The study supports the hypothesis that a selected group of WUS patients may be suitable for thrombolysis. PMID- 26370240 TI - Finite mixture clustering of human tissues with different levels of IGF-1 splice variants mRNA transcripts. AB - BACKGROUND: This study addresses a recurrent biological problem, that is to define a formal clustering structure for a set of tissues on the basis of the relative abundance of multiple alternatively spliced isoforms mRNAs generated by the same gene. To this aim, we have used a model-based clustering approach, based on a finite mixture of multivariate Gaussian densities. However, given we had more technical replicates from the same tissue for each quantitative measurement, we also employed a finite mixture of linear mixed models, with tissue-specific random effects. RESULTS: A panel of human tissues was analysed through quantitative real-time PCR methods, to quantify the relative amount of mRNA encoding different IGF-1 alternative splicing variants. After an appropriate, preliminary, equalization of the quantitative data, we provided an estimate of the distribution of the observed concentrations for the different IGF-1 mRNA splice variants in the cohort of tissues by employing suitable kernel density estimators. We observed that the analysed IGF-1 mRNA splice variants were characterized by multimodal distributions, which could be interpreted as describing the presence of several sub-population, i.e. potential tissue clusters. In this context, a formal clustering approach based on a finite mixture model (FMM) with Gaussian components is proposed. Due to the presence of potential dependence between the technical replicates (originated by repeated quantitative measurements of the same mRNA splice isoform in the same tissue) we have also employed the finite mixture of linear mixed models (FMLMM), which allowed to take into account this kind of within-tissue dependence. CONCLUSIONS: The FMM and the FMLMM provided a convenient yet formal setting for a model-based clustering of the human tissues in sub-populations, characterized by homogeneous values of concentrations of the mRNAs for one or multiple IGF-1 alternative splicing isoforms. The proposed approaches can be applied to any cohort of tissues expressing several alternatively spliced mRNAs generated by the same gene, and can overcome the limitations of clustering methods based on simple comparisons between splice isoform expression levels. PMID- 26370241 TI - Mating induces the expression of immune- and pH-regulatory genes in the utero vaginal junction containing mucosal sperm-storage tubuli of hens. AB - The female chicken, as with other species with internal fertilization, can tolerate the presence of spermatozoa within specialized sperm-storage tubuli (SST) located in the mucosa of the utero-vaginal junction (UVJ) for days or weeks, without eliciting an immune response. To determine if the oviduct alters its gene expression in response to sperm entry, segments from the oviduct (UVJ, uterus, isthmus, magnum and infundibulum) of mated and unmated (control) hens, derived from an advanced inter-cross line between Red Junglefowl and White Leghorn, were explored 24 h after mating using cDNA microarray analysis. Mating shifted the expression of fifteen genes in the UVJ (53.33% immune-modulatory and 20.00% pH-regulatory) and seven genes in the uterus, none of the genes in the latter segment overlapping the former (with the differentially expressed genes themselves being less related to immune-modulatory function). The other oviductal segments did not show any significant changes. These findings suggest sperm deposition causes a shift in expression in the UVJ (containing mucosal SST) and the uterus for genes involved in immune-modulatory and pH-regulatory functions, both relevant for sperm survival in the hen's oviduct. PMID- 26370242 TI - Impact of gene polymorphisms of gonadotropins and their receptors on human reproductive success. AB - Gonadotropins and their receptors' genes carry several single-nucleotide polymorphisms resulting in endocrine genotypes modulating reproductive parameters, diseases, and lifespan leading to important implications for reproductive success and potential relevance during human evolution. Here we illustrate common genotypes of the gonadotropins and gonadotropin receptors' genes and their clinical implications in phenotypes relevant for reproduction such as ovarian cycle length, age of menopause, testosterone levels, polycystic ovary syndrome, and cancer. We then discuss their possible role in human reproduction and adaptation to the environment. Gonadotropins and their receptors' variants are differently distributed among human populations. Some hints suggest that they may be the result of natural selection that occurred in ancient times, increasing the individual chance of successful mating, pregnancy, and effective post-natal parental cares. The gender-related differences in the regulation of the reproductive endocrine systems imply that many of these genotypes may lead to sex-dependent effects, increasing the chance of mating and reproductive success in one sex at the expenses of the other sex. Also, we suggest that sexual conflicts within the FSH and LH-choriogonadotropin receptor genes contributed to maintain genotypes linked to subfertility among humans. Because the distribution of polymorphic markers results in a defined geographical pattern due to human migrations rather than natural selection, these polymorphisms may have had only a weak impact on reproductive success. On the contrary, such genotypes could acquire relevant consequences in the modern, developed societies in which parenthood attempts often occur at a later age, during a short, suboptimal reproductive window, making clinical fertility treatments necessary. PMID- 26370243 TI - Ethical considerations in malaria research proposal review: empirical evidence from 114 proposals submitted to an Ethics Committee in Thailand. AB - BACKGROUND: Malaria research is typically conducted in developing countries in areas of endemic disease. This raises specific ethical issues, including those related to local cultural concepts of health and disease, the educational background of study subjects, and principles of justice at the community and country level. Research Ethics Committees (RECs) are responsible for regulating the ethical conduct of research, but questions have been raised whether RECs facilitate or impede research, and about the quality of REC review itself. This study examines the review process for malaria research proposals submitted to the Ethics Committee of the Faculty of Tropical Medicine at Mahidol University, Thailand. METHODS: Proposals for all studies submitted for review from January 2010 to December 2014 were included. Individual REC members' reviewing forms were evaluated. Ethical issues (e.g., scientific merit, risk-benefit, sample size, or informed-consent) raised in the forms were counted and analysed according to characteristics, including study classification/design, use of specimens, study site, and study population. RESULTS: All 114 proposals submitted during the study period were analysed, comprising biomedical studies (17 %), drug trials (13 %), laboratory studies (24 %) and epidemiological studies (46 %). They included multi site (13 %) and international studies (4 %), and those involving minority populations (28 %), children (17 %) and pregnant women (7 %). Drug trials had the highest proportion of questions raised for most ethical issues, while issues concerning privacy and confidentiality tended to be highest for laboratory and epidemiology studies. Clarifications on ethical issues were requested by the ethics committee more for proposals involving new specimen collection. Studies involving stored data and specimens tended to attract more issues around privacy and confidentiality. Proposals involving minority populations were more likely to raise issues than those that did not. Those involving vulnerable populations were more likely to attract concerns related to study rationale and design. CONCLUSIONS: This study stratified ethical issues raised in a broad spectrum of research proposals. The Faculty of Tropical Medicine at Mahidol University is a significant contributor to global malaria research output. The findings shed light on the ethical review process that may be useful for stakeholders, including researchers, RECs and sponsors, conducting malaria research in other endemic settings. PMID- 26370244 TI - Stress Testing of an Artificial Pancreas System With Pizza and Exercise Leads to Improvements in the System's Fuzzy Logic Controller. AB - BACKGROUND: Under controlled conditions, the Dose Safety artificial pancreas (AP) system controller, which utilizes "fuzzy logic" (FL) methodology to calculate and deliver appropriate insulin dosages based on changes in blood glucose, successfully managed glycemic excursions. The aim of this study was to show whether stressing the system with pizza (high carbohydrate/high fat) meals and exercise would reveal deficits in the performance of the Dose Safety FL controller (FLC) and lead to improvements in the dosing matrix. METHODS: Ten subjects with type 1 diabetes (T1D) were enrolled and participated in 30 studies (17 meal, 13 exercise) using 2 versions of the FLC. After conducting 13 studies with the first version (FLC v2.0), interim results were evaluated and the FLC insulin-dosing matrix was modified to create a new controller version (FLC v2.1) that was validated through regression testing using v2.0 CGM datasets prior to its use in clinical studies. The subsequent 17 studies were performed using FLC v2.1. RESULTS: Use of FLC v2.1 vs FLC v2.0 in the pizza meal tests showed improvements in mean blood glucose (205 mg/dL vs 232 mg/dL, P = .04). FLC v2.1 versus FLC v2.0 in exercise tests showed improvements in mean blood glucose (146 mg/dL vs 201 mg/dL, P = .004), percentage time spent >180 mg/dL (19.3% vs 46.7%, P = .001), and percentage time spent 70-180 mg/dL (80.0% vs 53.3%, P = .002). CONCLUSION: Stress testing the AP system revealed deficits in the FLC performance, which led to adjustments to the dosing matrix followed by improved FLC performance when retested. PMID- 26370246 TI - A challenging case of squamous metaplasia in a pleomorphic adenoma: diagnostic and clinical pitfalls. AB - Squamous metaplasia in a pleomorphic adenoma (PA) has been reported, but rarely has it been documented as being extensive enough to cause significant misdiagnosis. We present a case of a 37-year-old man presenting with a 1.7-cm minor salivary gland PA of the palate. It exhibited extensive squamous metaplasia mimicking a squamous cell carcinoma (SCC) on multiple preoperative biopsies. The final diagnosis was only made after a complete oncological excision with margins and free flap reconstruction. Florid squamous metaplasia in a PA, although rare, should be recognized and distinguished from SCC. Failure to differentiate these entities can lead to patient overtreatment. PMID- 26370245 TI - A cross-sectional study of the feasibility of pharmacy-delivered harm reduction services among people who inject drugs in Xichang, China. AB - BACKGROUND: HIV prevalence is high in Liangshan, China (1.1 %). In 2012, people who inject drugs (PWID) in Xichang, the capital city, contributed to 60.0 % of the HIV infections. The goal of the current study was to examine the feasibility of implementing pharmacy-delivered harm reduction services (PDHRS) for PWID. METHODS: Face-to-face structured interviews with 403 PWID included questions on PWID's experiences of syringe services and their specific experiences, acceptance, and potential usage of PDHRS. RESULTS: There were some reports of harassment/bad treatment from pharmacists (12.2 %) and police (17.6 %). Non prescription syringe sales (NPSS) from pharmacies in single piece were the main source (82.1 %) of syringes. 72.5 % of PWID reported visiting 31.5 % of the identified pharmacies. Most (74.7 %) PWID disposed of their used syringes by throwing them away. Only one PWID brought used syringes back to a pharmacy in the past 30 days. Half of the PDHRS, such as printed materials about HIV, Hepatitis C and STIs; risk reduction services; (16.9 %) and sharps container to dispose of syringes (0.2 %) were offered by a few pharmacies (<20 % for each service). The acceptance rates among PWID toward currently offered services were high (>=91.1 %). All potential PDHRS were acceptable by most (68-95.3 %) PWID, and correspondingly 67-94.5 % of PWID reported they would use each service if offered. CONCLUSIONS: NPSS from pharmacies provided many PWID in Liangshan with new syringes. However, disposal of used syringes was problematic. At the time of investigation, half of 16 assessed PDHRS were already available in pharmacies in Xichang. PWID were ready to use all the potential PDHRS and14 of 16 PDHRS were feasible to provide. HIV testing kits may be available in pharmacies in the future. Many pharmacy-delivered harm reduction services are feasible and acceptable among PWID in Xichang, China. PMID- 26370247 TI - Gadd45gamma regulates cardiomyocyte death and post-myocardial infarction left ventricular remodelling. AB - AIMS: Post-infarction remodelling is accompanied and influenced by perturbations in mitogen-activated protein kinase (MAPK) signalling. The growth arrest and DNA damage-inducible 45 (Gadd45) proteins are small acidic proteins involved in DNA repair and modulation of MAPK activity. Little is known about the role of Gadd45 in the heart. Here, we explored the potential contribution of Gadd45 gamma (gamma) isoform to the acute and late phase of heart failure (HF) after myocardial infarction (MI) and determined the mechanisms underlying Gadd45gamma actions. METHODS AND RESULTS: The Gadd45gamma isoform is up-regulated in murine cardiomyocytes subjected to simulated ischaemia and in the mouse heart during MI. To mimic the situation observed during MI, we enhanced Gadd45gamma content in cardiomyocytes with a single injection of an adeno-associated viral (AAV9) vector encoding Gadd45gamma under the cTNT promoter. Gadd45gamma overexpression induces cardiomyocyte apoptosis, fibrosis, left ventricular dysfunction, and HF. On the other hand, genetic deletion of Gadd45gamma in knockout mice confers resistance to ischaemic injury, at least in part by limiting cardiomyocyte apoptosis. Mechanistically, Gadd45gamma activates receptor-interacting protein 1 (RIP1) and caspase-8 in a p38 MAPK-dependent manner to promote cardiomyocyte death. CONCLUSION: This work is the first to demonstrate that Gadd45gamma accumulation during MI promotes the development and persistence of HF by inducing cardiomyocyte apoptosis in a p38 MAPK-dependent manner. We clearly identify Gadd45gamma as a therapeutic target in the development of HF. PMID- 26370249 TI - Advances in Molecular Structure and Interaction Studies Using Near-Infrared Spectroscopy. PMID- 26370248 TI - Different combinations of atomic interactions predict protein-small molecule and protein-DNA/RNA affinities with similar accuracy. AB - Interactions between proteins and other molecules play essential roles in all biological processes. Although it is widely held that a protein's ligand specificity is determined primarily by its three-dimensional structure, the general principles by which structure determines ligand binding remain poorly understood. Here we use statistical analyses of a large number of protein-ligand complexes with associated binding-affinity measurements to quantitatively characterize how combinations of atomic interactions contribute to ligand affinity. We find that there are significant differences in how atomic interactions determine ligand affinity for proteins that bind small chemical ligands, those that bind DNA/RNA and those that interact with other proteins. Although protein-small molecule and protein-DNA/RNA binding affinities can be accurately predicted from structural data, models predicting one type of interaction perform poorly on the others. Additionally, the particular combinations of atomic interactions required to predict binding affinity differed between small-molecule and DNA/RNA data sets, consistent with the conclusion that the structural bases determining ligand affinity differ among interaction types. In contrast to what we observed for small-molecule and DNA/RNA interactions, no statistical models were capable of predicting protein-protein affinity with >60% correlation. We demonstrate the potential usefulness of protein-DNA/RNA binding prediction as a possible tool for high-throughput virtual screening to guide laboratory investigations, suggesting that quantitative characterization of diverse molecular interactions may have practical applications as well as fundamentally advancing our understanding of how molecular structure translates into function. PMID- 26370250 TI - Critical Flicker Fusion Predicts Executive Function in Younger and Older Adults. AB - Critical flicker fusion (CFF), a measure of visual processing speed, has often been regarded as a basic metric underlying a number of higher cognitive functions. To test this, we measured CFF, global cognition, and several cognitive subdomains. Because age is a strong covariate for most of these variables, both younger (n = 72) and older (n = 57) subjects were measured. Consistent with expectations, age was inversely related to CFF and performance on all of the cognitive measures except for visual memory. In contrast, age-adjusted CFF thresholds were only positively related to executive function. Results showed that CFF predicted executive function across both age groups and accounted for unique variance in performance above and beyond age and global cognitive status. The current findings suggest that CFF may be a unique predictor of executive dysfunction. PMID- 26370251 TI - Dimethyl adipimidate/Thin film Sample processing (DTS); A simple, low-cost, and versatile nucleic acid extraction assay for downstream analysis. AB - Sample processing, especially that involving nucleic acid extraction, is a prerequisite step for the isolation of high quantities of relatively pure DNA for downstream analyses in many life science and biomedical engineering studies. However, existing methods still have major problems, including labor-intensive time-consuming methods and high costs, as well as requirements for a centrifuge and the complex fabrication of filters and membranes. Here, we first report a versatile Dimethyl adipimidate/Thin film based Sample processing (DTS) procedure without the limitations of existing methods. This procedure is useful for the extraction of DNA from a variety of sources, including 6 eukaryotic cells, 6 bacteria cells, and 2 body fluids in a single step. Specifically, the DTS procedure does not require a centrifuge and has improved time efficiency (30 min), affordability, and sensitivity in downstream analysis. We validated the DTS procedure for the extraction of DNA from human body fluids, as well as confirmed that the quality and quantity of the extracted DNA were sufficient to allow robust detection of genetic and epigenetic biomarkers in downstream analysis. PMID- 26370253 TI - Soil N retention and nitrate leaching in three types of dunes in the Mu Us desert of China. AB - A large reservoir of soil nitrate in desert subsoil zones has been demonstrated in previous studies; however, information on the subsoil nitrate reservoir and its distribution characteristics in the deserts of China is still limited. This study investigated the distribution patterns of soil total nitrogen (N), nitrate, ammonium, and stable isotopic ratios of (15)N (delta(15)N) in shallow (1 m) and subsoil (5 m) profiles in three types of dunes in the Mu Us desert of China. We found that soil N retention of the fixed and semi-fixed dunes followed a progressive nutrient depletion pattern in shallow soil profiles, whereas the subsoil nitrate of the fixed, semi-fixed and mobile dunes maintained a conservative accumulation pattern. The results indicate that the subsoil of the Mu Us desert may act as a reservoir of available nitrate. Furthermore, a soil delta(15)N analysis indicate that the nitrate content of the fixed dune is likely derived from soil nitrification, whereas the nitrate content in the mobile dune is derived from atmospheric nitrate deposition. Within the context of looming climate change and intensifying human activities, the subsoil nitrate content in the deserts of northern China could become mobilized and increase environmental risks to groundwater. PMID- 26370252 TI - Urinary isoflavonoids and risk of type 2 diabetes: a prospective investigation in US women. AB - To examine the association between urinary excretion of isoflavonoids and risk of type 2 diabetes (T2D), we conducted a nested case-control study among 1111 T2D pairs identified during 1995-2008 in the Nurses' Health Study (NHS) and NHSII, who were free of diabetes, CVD and cancer at urine sample collection. Urinary excretion of daidzein and genistein, as well as their metabolites O desmethylangolensin (O-DMA), dihydrogenistein (DHGE) and dihydrodaidzein (DHDE) was assayed using liquid chromatography MS. Self-reported T2D incident cases were confirmed using a validated questionnaire. Higher urinary excretion of daidzein and genistein was associated with a lower risk of T2D in the combined cohorts. Comparing extreme tertiles of the urinary markers, the OR of T2D were 0.71 (95 % CI 0.55, 0.93) for daidzein and 0.74 (95 % CI 0.56, 0.97) for genistein, although the test for linear trend was not significant for genistein (P trend=0.03 and 0.15, respectively). DMA, DHDE and DHGE were non-significantly associated with a lower T2D risk. The inverse association of daidzein with T2D risk was stronger among post-menopausal women who did not use hormone replacement therapy (P interaction=0.001): the OR was 0.58 (95 % CI 0.34, 0.97) comparing extreme tertiles among these women. In conclusion, urinary excretion of isoflavones was associated with a lower T2D risk in US women, especially among post-menopausal women who did not use hormone. Further research is warranted to replicate these observations among western populations with similarly low overall isoflavone intake. PMID- 26370255 TI - Barriers to care and quality of primary care services in children with sickle cell disease. AB - AIMS: The aims of this study were: to (1) identify barriers to care in children with sickle cell disease; (2) examine the quality of primary care services received by these children and (3) examine the relationship between barriers to care and quality of primary care services in children with sickle cell disease. BACKGROUND: Effective management in children with sickle cell disease requires early access to a comprehensive range of preventive screenings, urgent care treatments for vaso-occlusive pain crisis and ongoing prophylactic treatments. DESIGN: A cross-sectional survey of parents of children with sickle cell disease was conducted between April-September 2011. METHODS: Parents of children with sickle cell disease completed the Barriers to Care Questionnaire and Parent's Perceptions of Primary Care. RESULTS: Parents of children with sickle cell disease (n = 38) reported health system barriers such as inability to contact doctors or clinics, extended wait times and inconvenient clinic hours. Some barriers were reported more frequently among children with concurrent sickle cell disease and asthma, compared with those children without a concurrent asthma condition. Parents who reported more barriers were least likely to perceive their care as accessible, comprehensive and coordinated. CONCLUSIONS: Minimizing healthcare barriers may improve the quality of primary care services received by children with sickle cell disease and consequently prevent complications associated with sickle cell disease. IMPLICATIONS FOR NURSING PRACTICE: Nurses and other care providers need to identify healthcare barriers, so that access, coordination, comprehensiveness and overall quality of primary care services may be improved in children with sickle cell disease. PMID- 26370254 TI - Gas5 Exerts Tumor-suppressive Functions in Human Glioma Cells by Targeting miR 222. AB - Aberrant expression of noncoding RNAs in glioma cells, including long noncoding RNAs (lncRNAs) and microRNAs, may participate in the progression of glioma. Encoded by Growth Arrest-Specific 5 (GAS5) gene, lncRNA Gas5 was reported to be a negative regulator for survival and proliferation of several cancers. Here, Gas5 is found to be downregulated in glioma specimens and U87 and U251 glioma cell lines. We showed that the introduction of Gas5 by plasmid transfection increased the expression of tumor suppressor Bcl-2-modifying factor (bmf) and Plexin C1 via directly targeting and reducing the expression of miR-222. Downregulated expression of miR-222 inhibited U87 and U251 cell proliferation and promoted the apoptosis by upregulating bmf. As downstream signaling molecules of bmf, Bcl-2 and Bax were involved in the process. Meanwhile, knockdown of miR-222 attenuated U87 and U251 cell migration and invasion by upregulating Plexin C1, and cofilin was a crucial regulator targeted by Plexin C1. Gas5 combined with the knockdown of miR-222 resulted in the smallest tumor volumes and the longest survivals of nude mice in vivo. In summary, we show that Gas5 suppresses tumor malignancy by downregulating miR-222, which may serve as a promising therapy for glioma. PMID- 26370256 TI - Prognostic relevance of stromal CD26 expression in rectal cancer after chemoradiotherapy. AB - BACKGROUND: CD26 is a transmembrane glycoprotein whose role in various types of malignancies, along with the potential therapeutic and diagnostic targets, has been evaluated. Preoperative chemoradiotherapy (CRT) is an effective tool for local control of rectal cancer, but the rate of disease recurrence remains high. The aim of this study was to clarify the association between CD26 expression and rectal cancer after preoperative CRT. METHODS: A total of 85 patients with rectal cancer who had undergone preoperative CRT were enrolled in this study. We investigated CD26 expression in residual tumors and the surrounding stromal tissue using immunohistochemistry. Additionally, stromal CD26 gene expression was assessed by real-time quantitative polymerase chain reaction. RESULTS: Patients with high CD26 expression in cancer tissue more frequently had serosal invasion, vascular invasion, and a poor pathological response. High expression of CD26 in the tumor stroma was significantly correlated with histology and tumor recurrence. High CD26 expression in the stroma, but not the tumor itself, was significantly correlated with a poor prognosis. Patients expressing CD26 in the tumor stroma, based on transcriptional analysis, also had a significantly poorer prognosis than those without the expression. In multivariate analysis, lymph node metastasis and high stromal CD26 expression were identified as independent prognostic factors in patients with rectal cancer after neoadjuvant CRT. CONCLUSION: Stromal CD26 expression after preoperative CRT was significantly associated with tumor recurrence and prognosis in rectal cancer patients. Our data suggest that stromal CD26 plays an important role and is a potential therapeutic target in tumor relapse. PMID- 26370258 TI - Novel use of the NexfinTM HD monitor for real-time physiological assessment of blood flow during creation of an upper extremity arteriovenous fistula. PMID- 26370259 TI - Erratum to: A prospective observational study comparing a physiological scoring system with time-based discharge criteria in pediatric ambulatory surgical patients. AB - Erratum to: Can J Anesth/J Can Anesth DOI 10.1007/s12630-015-0428-6. In the published version, the first phrase of the introduction was incorrect and should read as follows: Since the inception of the postanesthesia care unit (PACU) in 1923, the question of when it is safe to discharge a patient has remained contentious. The publisher apologizes most sincerely for this typesetting error. PMID- 26370257 TI - Stated and Revealed Preferences for Funding New High-Cost Cancer Drugs: A Critical Review of the Evidence from Patients, the Public and Payers. AB - BACKGROUND: The growing focus on patient-centred care has encouraged the inclusion of patient and public input into payer drug reimbursement decisions. Yet, little is known about patient/public priorities for funding high-cost medicines, and how they compare to payer priorities applied in public funding decisions for new cancer drugs. OBJECTIVES: The aim was to identify and compare the funding preferences of cancer patients and the general public against the criteria used by payers making cancer drug funding decisions. METHODS: A thorough review of the empirical, peer-reviewed English literature was conducted. Information sources were PubMed, EMBASE, MEDLINE, Web of Science, Business Source Complete, and EconLit. Eligible studies (1) assessed the cancer drug funding preferences of patients, the general public or payers, (2) had pre-defined measures of funding preference, and (3) had outcomes with attributes or measures of 'value'. The quality of included studies was evaluated using a health technology assessment-based assessment tool, followed by extraction of general study characteristics and funding preferences, which were categorized using an established WHO-based framework. RESULTS: Twenty-five preference studies were retrieved (11 quantitative, seven qualitative, seven mixed-methods). Most studies were published from 2005 onward, with the oldest dating back to 1997. Two studies evaluated both patient and public perspectives, giving 27 total funding perspectives (41 % payer, 33 % public, 26 % patients). Of 41 identified funding criteria, payers consider the most (35), the general public considers fewer (23), and patients consider the fewest (12). We identify four unique patient criteria: financial protection, access to medical information, autonomy in treatment decision making, and the 'value of hope'. Sixteen countries/jurisdictions were represented. CONCLUSIONS: Our results suggest that (1) payers prioritize efficiency (health gains per dollar), while citizens (patients and the general public) prioritize equity (equal access to cancer medicines independent of cost or effectiveness), (2) citizens prioritize few criteria relevant to payers, and (3) citizens prioritize several criteria not considered by payers. This can explain why payer and citizen priorities clash when new cancer medicines are denied public funding. PMID- 26370260 TI - Anesthetic management of a parturient with hypermobility phenotype but possible vascular genotype Ehlers-Danlos syndrome. AB - PURPOSE: We describe a case of a term parturient previously clinically diagnosed with hypermobility type Ehlers-Danlos syndrome (EDS) but later diagnosed with a genotype that may be associated with vascular type EDS. CLINICAL FEATURES: This 26-yr-old primigravida had been clinically diagnosed with hypermobility type EDS prior to her pregnancy. Nevertheless, subsequent genetic testing during pregnancy revealed a heterozygous variant of unknown significance in the COL3A1 gene causative for vascular type EDS. A multidisciplinary decision was made to prioritize the phenotype rather than the genotype in regard to clinical management of labour. An induced labour was planned with instrument-assisted vaginal delivery. We elected to proceed with placement of an epidural catheter for provision of labour analgesia and anesthesia during delivery. Both maternal and neonatal outcomes were excellent. CONCLUSION: The risk of severe morbidity and mortality in parturients with vascular EDS has warranted recommendations for modified management of labour, particularly regarding mode and timing of delivery. Nevertheless, a multidisciplinary approach and consideration of phenotype rather than genotype alone were instrumental in the successful management of this patient. Genetic testing of patients who display features of EDS and/or who have a positive family history of the disease is important in the preparation for labour and delivery. In the absence of convincing signs of vascular EDS and a negative family history, it may be rational to offer certain parturients neuraxial anesthesia and a trial of vaginal labour. PMID- 26370261 TI - Relationship between CBCT and panoramic images of the morphology and angulation of the posterior mandibular jaw bone. AB - PURPOSE: We determined actual bucco-lingual angulation values and morphological variations of residual bone in the mandibular posterior edentulous region using cone-beam computed tomography (CBCT) and panoramic radiography. A second aim was to investigate whether it was possible to predict bone morphology from panoramic radiographs. METHODS: Data were collected from 77 consecutive patients referred for both CBCT and panoramic radiography in our department. Two-dimensional and three-dimensional images of the probable implant placement region were investigated. The bucco-lingual angulation values and crest type were determined directly from the cross-sectional images of the posterior edentulous region. The edentulous region was divided into three groups: second premolar, first molar, or second molar region. The observations were evaluated by the computer software, SPSS 22.0 (SPSS Inc. Chicago, USA). The crest type was classified into three groups: type U, type C, or type P. Kappa statistics, Kolmogorov-Smirnov tests, ANOVA, and Kruskal-Wallis tests were used in statistical analyses. The significance level was set at p < 0.05. RESULTS: Type C was more frequent in the second premolar region and the crest type had changed to type U in the second molar region. The predictability of the type U was highest in the second molar region. Moderate agreement was found in the predictability of type U in the molars (kappa = 0.602). The mean value of bucco-lingual angulation was highest in the second molar region, followed by the first molar region. There were statistically significant differences between the bucco-lingual angulation of the crest types in the second premolar and first molar regions (p < 0.05). CONCLUSIONS: Bucco-lingual angulation values and morphology change through the posterior mandible. Type U was predicted at a higher rate in the second molar region from panoramic radiographs. These results demonstrate predicting high-risk areas in the posterior mandible for implant therapy from panoramic radiography. PMID- 26370262 TI - Different stimulation protocols for oocyte cryropreservation in oncological patients: a retrospective analysis of single university centre. AB - OBJECTIVE: To analyze the results obtain in cancer patients who receive the same controlled ovarian stimulation protocol, started in two different moments of the menstrual cycle, follicular or luteal phase. The stimulation is performed before cancer treatment in order to preserve fertility through oocytes cryopreservation. STUDY DESIGN: The study is a retrospective analysis about 25 cancer patients at our centre, Department of Reproductive Medicine of University of Pisa, in order to preserve their fertility before cancer treatment. Patients are divided into two groups depending on the menstrual cycle phase, follicular or luteal phase, at the moment of first examination. Standard stimulation protocol with gonadotropins is administered in the follicular group, whereas in the second group we use GnRH (gonadotropin-releasing hormone) antagonist before gonadotropins administration in order to have a rapid luteolysis. The outcome measures are the number of days needed before starting procedure, duration of stimulation, cumulative dosage of gonadotropins number of oocyte retrieved and percentage of mature oocytes. RESULTS: Any difference showed between two groups based on days of stimulation, total amount of gonadotropins administered and the number of good mature quality oocytes was retrieved. The real difference is the number of days needed to start the procedure, lesser in the luteal group. CONCLUSIONS: This study suggests that oocytes can be obtained before cancer treatment, irrespective of menstrual cycle phase without compromising the efficacy of procedure. Moreover, starting ovarian stimulation anytime during menstrual cycle allows the patients to not postpone the beginning of cancer treatment. Different stimulation protocols, according to different kinds of disease, are available in order to obtain the maximum results without any complication for patients. PMID- 26370263 TI - Systematic review of evidence to support the theory of psychobiotics. AB - CONTEXT: The theory that supplemented probiotic bacteria could affect psychological outcomes has recently been outlined in narrative reviews; to date, however, this area of research has not been systematically reviewed. OBJECTIVE: The objective of this review was to compare the effects of probiotics with those of placebo on psychological outcomes and symptoms of psychiatric disorders. DATA SOURCES: The Cochrane Central Register of Controlled Trials, MEDLINE, Embase, PubMed, PsycINFO, and PsycARTICLES databases were searched electronically for studies published up to July 17, 2014. Reference lists of relevant articles were searched manually. STUDY SELECTION: Only double-blind, randomized, placebo controlled human trials that used a standardized, validated scale to assess the effects of probiotic interventions compared with placebo on psychological outcomes or symptoms of psychiatric disorders were included. DATA EXTRACTION: Two researchers independently assessed trials and evaluated them for methodological quality. Data were extracted from the included studies using a data extraction form. DATA SYNTHESIS: Ten trials met the inclusion criteria. Overall, there is very limited evidence for the efficacy of probiotic interventions in psychological outcomes. The evidence base is incomplete and lacks applicability. CONCLUSIONS: More trials are necessary before any inferences can be made about the efficacy of probiotics in mental health applications. PMID- 26370264 TI - Development of technologies for placement of perineural catheters. AB - Continuous peripheral nerve block (CPNB) success is largely dependent on placement of the catheter close enough to the nerve to allow effective and sustained analgesia following painful surgeries with a minimum volume of local anesthetic. One of the most common problems associated with CPNB involves accurate placement of the catheter tip, migration, and dislodgement of the catheter. This is of increasing importance now that catheters are left in place for prolonged periods of time to provide postoperative analgesia, and patients with peripheral nerve catheters are being discharged home with ambulatory pumps. In response to the challenges of providing safe, effective, and consistently reliable analgesia, research and development in this field is expanding rapidly. This review article presents results from recent publications addressing the subject of peripheral nerve catheter localization. PMID- 26370265 TI - Modulation of AMPA receptor mediated current by nicotinic acetylcholine receptor in layer I neurons of rat prefrontal cortex. AB - Layer I neurons in the prefrontal cortex (PFC) exhibit extensive synaptic connections with deep layer neurons, implying their important role in the neural circuit. Study demonstrates that activation of nicotinic acetylcholine receptors (nAChRs) increases excitatory neurotransmission in this layer. Here we found that nicotine selectively increased the amplitude of AMPA receptor (AMPAR)-mediated current and AMPA/NMDA ratio, while without effect on NMDA receptor-mediated current. The augmentation of AMPAR current by nicotine was inhibited by a selective alpha7-nAChR antagonist methyllycaconitine (MLA) and intracellular calcium chelator BAPTA. In addition, nicotinic effect on mEPSC or paired-pulse ratio was also prevented by MLA. Moreover, an enhanced inward rectification of AMPAR current by nicotine suggested a functional role of calcium permeable and GluA1 containing AMPAR. Consistently, nicotine enhancement of AMPAR current was inhibited by a selective calcium-permeable AMPAR inhibitor IEM-1460. Finally, the intracellular inclusion of synthetic peptide designed to block GluA1 subunit of AMPAR at CAMKII, PKC or PKA phosphorylation site, as well as corresponding kinase inhibitor, blocked nicotinic augmentation of AMPA/NMDA ratio. These results have revealed that nicotine increases AMPAR current by modulating the phosphorylation state of GluA1 which is dependent on alpha7-nAChR and intracellular calcium. PMID- 26370266 TI - The complete mitochondrial genome sequence and gene organization of Tridentiger trigonocephalus (Gobiidae: Gobionellinae) with phylogenetic consideration. AB - The complete mitochondrial genome plays an important role in studies of genome level characteristics and phylogenetic relationships. Here we determined the complete mitogenome sequence of Tridentiger trigonocephalus (Perciformes, Gobiidae), and discovered its phylogenetic relationship. This circular genome was 16 662 bp in length, and consisted of 37 typical genes, including 13 protein coding genes, 22 tRNA genes, and two rRNA genes. The gene order of T. trigonocephalus mitochondrial genome was identical to those observed in most other vertebrates. Of 37 genes, 28 were encoded by heavy strand, while the others were encoded by light strand. The phylogenetic tree constructed by 13 concatenated protein-coding genes showed that T. trigonocephalus was closest to T. bifasciatus, and then to T. barbatus among the 20 species within suborder Gobioidei. This work should facilitate the studies on population genetic diversity, and molecular evolution in Gobioidei fishes. PMID- 26370267 TI - Genome-wide expression profiling of microRNAs in poplar upon infection with the foliar rust fungus Melampsora larici-populina. AB - BACKGROUND: MicroRNAs (miRNAs) are small non-coding RNAs that regulate the gene expression of target mRNAs involved in plant growth, development, and abiotic stress and pathogen responses. Previous studies have reported miRNAs in Populus that respond to abiotic stresses, such as cold, heat, drought, flooding, high salt and mechanical stress. However, little is known about the regulatory roles of these molecules in the Populus response to the stress of foliar rust fungal infection. Here, we identified the miRNA profiles of Populus after inoculation with Melampsora larici-populina using high-throughput sequencing and bioinformatics analysis. Quantitative real-time PCR (qRT-PCR) was used to validate the expression levels of 10 miRNAs. RESULTS: A total of 90 known miRNAs belonging to 42 families and 378 novel miRNAs were identified from three small RNA libraries of Populus szechuanica infected with M. larici-populina isolates Sb052 and Th053 and a control. Comparative analysis revealed that the expression of 38 known miRNAs and 92 novel miRNAs in P. szechuanica after infection with different rust fungus isolates showed significant differences, and more miRNAs were suppressed during rust infection. Among the differentially expressed miRNAs, 7 known and 20 novel miRNAs were relevant to the rust fungus infection, and according to KEGG (Kyoto Encyclopaedia of Genes and Genomes) pathway analysis, these miRNAs primarily regulate genes encoding disease-resistance proteins, serine/threonine protein kinases, transcription factors, and related proteins. QRT-PCR analysis indicated that most miRNAs were up-regulated in the Sb052 library and down-regulated in the Th053 library at 48 h post-inoculation (hpi). CONCLUSIONS: These results demonstrate that the expression of miRNAs was altered in poplar under stress associated with M. larici-populina infection, and different temporal dynamics were observed in incompatible and compatible libraries. These findings suggest important roles for miRNA regulation in Populus upon infection with foliar rust fungus. PMID- 26370268 TI - Surgical fixation methods for tibial plateau fractures. AB - BACKGROUND: Fractures of the tibial plateau, which are intra-articular injuries of the knee joint, are often difficult to treat and have a high complication rate, including early-onset osteoarthritis. Surgical fixation is usually used for more complex tibial plateau fractures. Additionally, bone void fillers are often used to address bone defects caused by the injury. Currently there is no consensus on either the best method of fixation or bone void filler. OBJECTIVES: To assess the effects (benefits and harms) of different surgical interventions, and the use of bone void fillers, for treating tibial plateau fractures. SEARCH METHODS: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (12 September 2014), the Cochrane Central Register of Controlled Trials (2014 Issue 8), MEDLINE (1946 to September Week 1 2014), EMBASE (1974 to 2014 Week 36), trial registries (4 July 2014), conference proceedings and grey literature (4 July 2014). SELECTION CRITERIA: We included randomised and quasi randomised controlled clinical trials comparing surgical interventions for treating tibial plateau fractures and the different types of filler for filling bone defects. DATA COLLECTION AND ANALYSIS: Two review authors independently screened search results, selected studies, extracted data and assessed risk of bias. We calculated risk ratios (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes, with 95% confidence intervals (CIs). Only very limited pooling, using the fixed-effect model, was possible. Our primary outcomes were quality of life measures, patient-reported outcome measures of lower limb function and serious adverse events. MAIN RESULTS: We included six trials in the review, with a total of 429 adult participants, the majority of whom were male (63%). Three trials evaluated different types of fixation and three analysed different types of bone graft substitutes. All six trials were small and at substantial risk of bias. We judged the quality of most of the available evidence to be very low, meaning that we are very uncertain about these results.One trial compared the use of a circular fixator combined with insertion of percutaneous screws (hybrid fixation) versus standard open reduction and internal fixation (ORIF) in people with open or closed Schatzker types V or VI tibial plateau fractures. Results (66 participants) for quality of life scores using the 36-item Short Form Health Survey (SF-36)), Hospital for Special Surgery (HSS) scores and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function scores tended to favour hybrid fixation, but a benefit of ORIF could not be ruled out. Participants in the hybrid fixation group had a lower risk for an unplanned reoperation (351 per 1000 people compared with 450 in the ORIF group; 95% CI 197 fewer to 144 more) and were more likely to have returned to their pre-injury activity level (303 per 1000 people, compared with 121 in the ORIF group; 95% CI 15 fewer to 748 more). Results of the two groups were comparable for the WOMAC pain subscale and stiffness scores, but mean knee range of motion values were higher in the hybrid group.Another trial compared the use of a minimally invasive plate (LISS system) versus double-plating ORIF in 84 people who had open or closed bicondylar tibial plateau fractures. Nearly twice as many participants (22 versus 12) in the ORIF group had a bone graft. Quality of life, pain, knee range of motion and return to pre-injury activity were not reported. The trial provided no evidence of differences in HSS knee scores, complications or reoperation entailing implant removal or revision fixation. A quasi-randomised trial comparing arthroscopically-assisted percutaneous reduction and internal fixation versus standard ORIF reported results at 14 months in 58 people with closed Schatzker types II or III tibial plateau fracture. Quality of life, pain and return to pre-injury activity were not reported. There was very low quality evidence of higher HSS knee scores and higher knee range of motion values in the arthroscopically assisted group. No reoperations were reported.Three trials compared different types of bone substitute versus autologous bone graft (autograft) for managing bone defects. Quality of life, pain and return to pre-injury activity were not reported. Only one trial (25 participants) reported on lower limb function, finding good or excellent results in both groups for walking, climbing stairs, squatting and jumping at 12 months. The incidences of individual complications were similar between groups in all three trials. One trial found no cases of inflammatory response in the 20 participants receiving bone substitute, and two found no complications associated with the donor site in the autograft group (58 participants). However, all 38 participants in the autologous iliac bone graft group of one trial reported prolonged pain from the harvest site. Two trials reported similar range of motion results in the two groups, whereas the third trial favoured the bone substitute group. AUTHORS' CONCLUSIONS: Currently, there is insufficient evidence to ascertain the best method of fixation or the best method of addressing bone defects during surgery. However, the evidence does not contradict approaches aiming to limit soft-tissue dissection and damage or to avoid autograft donor site complications through using bone substitutes. Further well-designed, larger randomised trials are warranted. PMID- 26370269 TI - Modeling the energetic cost of cancer as a result of altered energy metabolism: implications for cachexia. AB - BACKGROUND: Cachexia affects most patients with incurable cancer. We hypothesize that in metastatic cancer the mass of the tumor as well as its level of anaerobic energy metabolism play a critical role in describing its energetic cost, which results in elevated resting energy expenditure and glucose utilization, leading to cachexia. Prior models of cancer cachexia may have underestimated the specific energetic cost of cancer as they have not taken the range of tumor mass and anaerobic energy metabolism fully into account. METHODS: We therefore modelled the energetic cost of cancer as a function of the percentage of energy the cancer produces anaerobically, based on resting energy expenditure, glucose turnover, glucose recycling, and oxygen consumption in cancer patients found in previous studies. RESULTS: Data from two clinical studies where tumor burden was estimated and resting energy expenditure or oxygen consumption were measured lead to a broad range of estimates of tumor cost from 190 to 470 kcal/kg tumor/day. These values will vary based of the percentage of energy the cancer produces anaerobically (from 0 to 100%), which in and of itself can alter the cost over a 2 to 3-fold range. In addition to the tumor cost/kg and the degree of anaerobic metabolism, the impact on a given individual patient will depend on tumor burden, which can exceed 1 kg in advanced metastatic disease. Considering these dimensions of tumor cost we are able to produce a 2-dimensional map of potential values, with an overall range of 100-1400 kcal/day. CONCLUSIONS: Quantifying the energetic cost of cancer may benefit an understanding of the tumor's causation of cachexia. Our estimates of the range of tumor cost include values that are higher than prior estimates and suggest that in metastatic disease the tumor cost could be expected to eclipse attempts to stabilize energy balance through nutrition support or by drug therapies. Tumor mass and the percentage of anaerobic metabolism in the tumor contribute to the cost of the tumor on the body and potentially lead directly to negative energy balance and increased muscle wasting. PMID- 26370270 TI - Enhanced purification of plasmid DNA isoforms by exploiting ionic strength effects during ultrafiltration. AB - The solution structure of plasmid DNA is known to be a strong function of solution conditions due to intramolecular electrostatic interactions between the charged phosphate groups along the DNA backbone. The objective of this work was to determine whether it was possible to enhance the use of ultrafiltration for separation of different plasmid isoforms by proper selection of the solution ionic strength and ion type. Experiments were performed with a 3.0 kbp plasmid using composite regenerated cellulose ultrafiltration membranes. The transmission of the linear isoform was nearly independent of solution ionic strength, but increased significantly with increasing filtrate flux due to the elongation of the highly flexible plasmid in the converging flow field into the membrane pores. In contrast, the transmission of the open-circular and supercoiled plasmids both increased with increasing NaCl or MgCl2 concentration due to the change in plasmid size and conformational flexibility. The effect of ionic strength was greatest for the supercoiled plasmid, providing opportunities for enhanced purification of this therapeutically active isoform. This behavior was confirmed using experiments performed with binary mixtures of the different isoforms. These results clearly demonstrate the potential for enhancing the performance of membrane systems for plasmid DNA separations by proper selection of the ionic conditions. PMID- 26370271 TI - Structural and biochemical characterization and evolutionary relationships of the fatty acid-binding protein 10 (Fabp10) of hake (Merluccius hubbsi). AB - A fatty acid-binding protein (FABP) from the liver of Argentine hake (Merluccius hubbsi) was isolated and characterized and its expression analyzed. The determination of its partial primary structures (72%) showed that it presents highest identity with Fabp10, commonly termed liver basic-type FABP. The evolutionary tree showed greater relationship between the Fabp10 of hake (Me Fabp10) and the Fabp10 and the Fabp10a of teleost fish. Me Fabp10 had low affinity for palmitic, oleic and palmitoleic acid and high affinity for bilirubin, lysophosphatidylcholine and lysophosphatidylethanolamine, all of them important in the metabolic functions of the liver. Me Fabp10 was able to bind only one cis-parinaric acid molecule and was found to be expressed only in the liver. PMID- 26370272 TI - Mobility of the first metatarsal-cuneiform joint in patients with and without hallux valgus: in vivo three-dimensional analysis using computerized tomography scan. AB - BACKGROUND: Hallux valgus (HV) deformity is closely correlated to the hypermobility of the first metatarsal-cuneiform joint, but adequate understanding of the three-dimentional (3D) mobility of this joint in normal or HV feet is lacking. This study was conducted to investigate the mobility of the first metatarsal-cuneiform joint in multiple planes during body weight-bearing conditions for both normal and HV patients. METHODS: A total of 10 female volunteers (20 feet) and 10 female HV patients (20 feet) participated in this study. Using a custom-made foot-loading device, computerized tomography (CT) scans of each pair of feet were taken under both unloaded and body weight-bearing conditions. 3D models were reconstructed for the first metatarsal and the medial cuneiform. Rotational and translational motions of the first metatarsal-cuneiform joint in multiple planes from unloaded to loaded conditions were quantitatively evaluated by reverse-engineering software. RESULTS: During body weight-bearing conditions, the first metatarsal-cuneiform joint in HV feet dorsiflexed at an average of 2.91 degrees (standard deviation, SD 1.71) versus 1.18 degrees (SD 0.47) in controls (t = 4.158, P = 0.001); supinated 2.17 degrees (SD 2.28) versus 0.98 degrees (SD 0.81) in controls (t = 2.080, P = 0.045); and internally rotated 2.65 degrees (SD 2.22) versus 0.96 degrees (SD 0.57) in controls (t = 3.114, P = 0.006). Moreover, the joint in HV feet widened significantly compared with the controls (t = 2.256, P = 0.030) and tended to translate more in the dorsal-plantar direction (t = 1.928, P = 0.063); the translation in the medial lateral direction was not significantly different between the two groups. CONCLUSIONS: During weight-loading process, the first metatarsal-cuneiform joint turns dorsiflexed, supinated, and internally rotated. For HV feet, hypermobility of the first metatarsal-cuneiform joint can be observed in multiple planes. This study promotes further understanding of the physiological and pathological mobility of the first metatarsal-cuneiform joint. PMID- 26370273 TI - The Health Service Use of Frequent Users of Telephone Helplines in a Cohort of General Practice Attendees with Depressive Symptoms. AB - We examined the relationship between frequent use of telephone helplines and health service use over time in a cohort of 789 general practice attendees with depressive symptoms. Telephone helpline use (no use, non-frequent use, frequent use) was measured at 3, 6, 9 and 12 months and analysed using ordered logistic regression. Sixteen participants (2 %) reported frequent use of telephone helplines. Reporting frequent use was associated with visiting multiple general practitioners, using emergency services and visiting mental health specialists in the previous 3 months. Despite this pattern of service use, there was evidence that these services were not meeting the needs of frequent users of telephone helplines, as they were also more likely to report dissatisfaction with their access to health services compared to non-frequent and non-users of telephone helplines. Our findings suggest that a model of care which addresses the complex needs of frequent users of telephone helplines is needed. PMID- 26370274 TI - 4-(2-Pyridylazo)-resorcinol Functionalized Thermosensitive Ionic Microgels for Optical Detection of Heavy Metal Ions at Nanomolar Level. AB - 4-(2-Pyridylazo)-resorcinol (PAR) functionalized thermosensitive ionic microgels (PAR-MG) were synthesized by a one-pot quaternization method. The PAR-MG microgels were spherical in shape with radius of ca. 166.0 nm and narrow size distribution and exhibited thermo-sensitivity in aqueous solution. The PAR-MG microgels could optically detect trace heavy metal ions, such as Cu(2+), Mn(2+), Pb(2+), Zn(2+), and Ni(2+), in aqueous solutions with high selectivity and sensitivity. The PAR-MG microgel suspensions exhibited characteristic color with the presence of various trace heavy metal ions, which could be visually distinguished by naked eyes. The limit of colorimetric detection (DL) was determined to be 38 nM for Cu(2+) at pH 3, 12 nM for Cu(2+) at pH 7, and 14, 79, 20, and 21 nM for Mn(2+), Pb(2+), Zn(2+), and Ni(2+), respectively, at pH 11, which was lower than (or close to) the United States Environmental Protection Agency standard for the safety limit of these heavy metal ions in drinking water. The mechanism of detection was attributed to the chelation between the nitrogen atoms and o-hydroxyl groups of PAR within the microgels and heavy metal ions. PMID- 26370276 TI - Survival, Reproduction and Growth of the Marine Amphipod, Leptocheirus plumulosus, Following Laboratory Exposure to Copper-Spiked Sediment. AB - Leptocheirus plumulosus was exposed for 28 days to Cu-spiked sediment at mean concentrations ranging from 44.4 to 605 mg Cu/kg dry sediment in a sediment/water test system designed to simulate natural conditions. The NOEC (no observed effect concentration)-LOEC (lowest observed effect concentration) range for the most sensitive endpoint of growth was 199-414 mg Cu/kg sediment. An IC50 for reproduction was estimated at 187 mg Cu/kg sediment. Mean Cu concentrations in pore water (PW) where significant effects were observed were 25.8 and 59.0 ug/L, while their respective concentrations in overlying water (OW) were 22.1 and 28.0 ug Cu/L. Copper concentrations were <=19.1 and <16.6 ug/L in PW and OW, respectively, at lower exposures where effects were not evident. Concentrations of Cu in marine sediment lower than sediment quality guidelines based on geochemical factors of acid volatile sulfide, organic carbon content (f OC), and sediment grain size (i.e., silt + clay) would appear not to result in adverse effects toward L. plumulosus. PMID- 26370275 TI - FDG-PET scans in patients with Kraepelinian and non-Kraepelinian schizophrenia. AB - We recruited 14 unmedicated patients with Kraepelinian schizophrenia (12 men and 2 women; mean age = 47 years old), 27 non-Kraepelinian patients (21 men and 6 women; mean age = 36.4 years old) and a group of 56 age- and sex-matched healthy volunteers. FDG positron emission tomography and MRI scans were coregistered for both voxel-by-voxel statistical mapping and stereotaxic regions of interest analysis. While both Kraepelinian and non-Kraepelinian patients showed equally lower uptake than healthy volunteers in the frontal lobe, the temporal lobes (Brodmann areas 20 and 21) showed significantly greater decreases in Kraepelinian than in non-Kraepelinian patients. Kraepelinian patients had lower FDG uptake in parietal regions 39 and 40, especially in the right hemisphere, while non Kraepelinian patients had similar reductions in the left. Only non-Kraepelinian patients had lower caudate FDG uptake than healthy volunteers. While both patient groups had lower uptake than healthy volunteers in the medial dorsal nucleus of the thalamus, Kraepelinian patients alone had higher uptake in the ventral nuclei of the thalamus. Kraepelinian patients also showed higher metabolic rates in white matter. Our results are consistent with other studies indicating that Kraepelinian schizophrenia is a subgroup of schizophrenia, characterized by temporal and right parietal deficits and normal rather than reduced caudate uptake. It suggests that Kraepelinian schizophrenia may be more primarily characterized by FDG uptake decreased in both the frontal and temporal lobes, while non-Kraepelinian schizophrenia may have deficits more limited to the frontal lobe. This is consistent with some neuropsychological and prognosis reports of disordered sensory information processing in Kraepelinian schizophrenia in addition to deficits in frontal lobe executive functions shared with the non-Kraepelinian subtype. PMID- 26370277 TI - Acute Toxicity and Genotoxicity of Carbendazim, Main Impurities and Metabolite to Earthworms (Eisenia foetida). AB - The acute toxicity and genotoxicity of carbendazim, two impurities (3-amino-2 hydroxyphenazine and 2,3-diaminophenazine) and one metabolite (2 aminobenzimidazole) to Eisenia foetida were assessed using artificial soil test and comet assay respectively. Acute toxicity results showed carbendazim was moderately toxic to the earthworms with 14 day-LC50 of 8.6 mg/kg dry soil while 3 amino-2-hydroxyphenazine, 2,3-diaminophenazine, and 2-aminobenzimidazole were of low toxicity with 14 day-LC50 values of 19.0, 14.9, and 27.7 mg/kg dry soil respectively (nominal concentration). The olive tail moment and percentage of DNA in the tail were used as genotoxicity indices, and carbendazim could significantly induce DNA damage to the earthworm coelomocytes with obviously positive dose- and duration-response relationships while the other three substances showed similar (p = 0.05) genotoxicity results to the negative controls in all of the tests. PMID- 26370278 TI - Assessment of Heavy Metal Pollution in Sediments of Inflow Rivers to Lake Taihu, China. AB - Lake Taihu, the third-largest freshwater body in China, has many functions, including drinking water supply, flood control, cultivation, navigation, and tourism. In this study, sediment samples were collected at 31 sites from 11 inflow rivers in 2012, to investigate the distribution and concentration of heavy metals copper (Cu), zinc (Zn), lead (Pb), nickel (Ni), and chromium (Cr), and to assess their potential ecological risk. The highest mean concentration was found for Zn, followed by Cu, Cr, Pb, and Ni. Generally, heavy metal pollution was more serious in Wu Jingang River and Caoqiao River, probably because they receive large amounts of wastewater from various local industrial enterprises. The potential ecological risk values of the heavy metals were larger than 120 in more than 25.8% of the sediment samples, indicating a very high risk. The largest ecological risk was due to copper. Furthermore, the results of a principal component analysis and subsequent analysis of variance showed that heavy metal concentrations in the sediment of inflow rivers were higher than those of the lake, which created a large hazard for the aquatic ecosystems of Lake Taihu. PMID- 26370279 TI - Bioaccumulation and Elimination of the Herbicide Clomazone in the Earthworms Eisenia fetida. AB - Acute toxicity, bioaccumulation, and elimination of herbicide clomazone in the earthworm Eisenia fetida were investigated in the different exposure systems. The LC50 values of clomazone on earthworms were 5.6 MUg cm(-2) in the contact filter paper test (48 h), 174.9 mg kg(-1) (7 days) and 123.4 mg kg(-1) (14 days) in artificial soil test, respectively. Clomazone could rapidly bioaccumulate in earthworms and reached the highest concentration after 3 days exposure, with the maximum concentrations of 9.0, 35.3 and 142.3 mg kg(-1) at 10.0, 40.0 and 160.0 mg kg(-1) of clomazone, respectively. Clomazone uptake showed a good correlation with exposure concentration. After the 14th day, clomazone declined to minimum value. About 74%-80% of accumulated clomazone was eliminated within 1 day after exposed to clomazone-free soil. However, a trace amount of clomazone persisted for a relatively long time in earthworms. PMID- 26370280 TI - Integrated protein function prediction by mining function associations, sequences, and protein-protein and gene-gene interaction networks. AB - MOTIVATIONS: Protein function prediction is an important and challenging problem in bioinformatics and computational biology. Functionally relevant biological information such as protein sequences, gene expression, and protein-protein interactions has been used mostly separately for protein function prediction. One of the major challenges is how to effectively integrate multiple sources of both traditional and new information such as spatial gene-gene interaction networks generated from chromosomal conformation data together to improve protein function prediction. RESULTS: In this work, we developed three different probabilistic scores (MIS, SEQ, and NET score) to combine protein sequence, function associations, and protein-protein interaction and spatial gene-gene interaction networks for protein function prediction. The MIS score is mainly generated from homologous proteins found by PSI-BLAST search, and also association rules between Gene Ontology terms, which are learned by mining the Swiss-Prot database. The SEQ score is generated from protein sequences. The NET score is generated from protein-protein interaction and spatial gene-gene interaction networks. These three scores were combined in a new Statistical Multiple Integrative Scoring System (SMISS) to predict protein function. We tested SMISS on the data set of 2011 Critical Assessment of Function Annotation (CAFA). The method performed substantially better than three base-line methods and an advanced method based on protein profile-sequence comparison, profile-profile comparison, and domain co occurrence networks according to the maximum F-measure. PMID- 26370281 TI - Can Disease-Specific Funding Harm Health? in the Shadow of HIV/AIDS Service Expansion. AB - This article examines the effect of introducing a new HIV/AIDS service-prevention of mother-to-child transmission of HIV (PMTCT)-on overall quality of prenatal and postnatal care. My results suggest that local PMTCT introduction in Zambia may have actually increased all-cause child mortality in the short term. There is some evidence that vaccinations may have declined in the short term in association with local PMTCT introduction, suggesting that the new service may have partly crowded out existing pediatric health services. PMID- 26370282 TI - The Long-Term Health Implications of Marital Disruption: Divorce, Work Limits, and Social Security Disability Benefits Among Men. AB - We provide new evidence on the long-term impact of divorce on work disability among U.S. men. Using data from the 2004 Survey of Income and Program Participation linked to U.S. Social Security Administration records, we assess the relationship between divorce and subsequent self-reports of work limitations and the receipt of federal disability benefits. The examination of self-reports and administrative records of medically qualified benefits provides dual confirmation of key relationships. We compare men who experienced a marital dissolution between 1975 and 1984 with continuously married men for 20 years following divorce using fixed-effects and propensity score matching models, and choose a sample to help control for selection into divorce. On average, we find that divorce is not associated with an increased probability of self-reported work limitations or receipt of disability benefits over the long run. However, among those who do not remarry, we do find that divorce increases men's long-term probability of both self-reported work limitations and federal disability benefit receipt. Lack of marital resources may drive this relationship. Alternative estimates that do not control for selection into divorce demonstrate that selection bias can substantially alter findings regarding the relationship between marital status changes and subsequent health. PMID- 26370283 TI - Phosphoproteomic analysis reveals Smarcb1 dependent EGFR signaling in Malignant Rhabdoid tumor cells. AB - BACKGROUND: The SWI/SNF ATP dependent chromatin remodeling complex is a multi subunit complex, conserved in eukaryotic evolution that facilitates nucleosomal re-positioning relative to the DNA sequence. In recent years the SWI/SNF complex has emerged to play a role in cancer development as various sub-units of the complex are found to be mutated in a variety of tumors. One core-subunit of the complex, which has been well established as a tumor suppressor gene is SMARCB1 (SNF5/INI1/BAF47). Mutation and inactivation of SMARCB1 have been identified as the underlying mechanism leading to Malignant Rhabdoid Tumors (MRT) and Atypical Teratoid/Rhabdoid Tumors (AT/RT), two highly aggressive forms of pediatric neoplasms. METHODS: We present a phosphoproteomic study of Smarcb1 dependent changes in signaling networks. The SILAC (Stable Isotopic Labeling of Amino Acids in Cell Culture) protocol was used to quantify in an unbiased manner any changes in the phosphoproteomic profile of Smarcb1 deficient murine rhabdoid tumor cell lines following Smarcb1 stable re-expression and under different serum conditions. RESULTS: This study illustrates broad changes in the regulation of multiple biological networks including cell cycle progression, chromatin remodeling, cytoskeletal regulation and focal adhesion. Specifically, we identify Smarcb1 dependent changes in phosphorylation and expression of the EGF receptor, demonstrate downstream signaling and show that inhibition of EGFR signaling specifically hinders the proliferation of Smarcb1 deficient cells. CONCLUSIONS: These results support recent findings regarding the effectivity of EGFR inhibitors in hindering the proliferation of human MRT cells and demonstrate that activation of EGFR signaling in Rhabdoid tumors is SMARCB1 dependent. PMID- 26370284 TI - Quality of working life of cancer survivors: development of a cancer-specific questionnaire. AB - PURPOSE: The aim of this study was to generate, and select quality of working life issues for the development of an initial version of the Quality of Working Life Questionnaire for Cancer Survivors (QWLQ-CS). METHODS: Quality of working life issues were generated through focus groups with cancer survivors and oncological occupational physicians, and interviews with employers, supervisors, and organization officers. A selection of these quality of working life issues was made based on relevance and importance by conducting an online questionnaire among the cancer survivors and oncological occupational physicians. Researchers formulated the issues into items for the QWLQ-CS. RESULTS: A total of 24 cancer survivors, six oncological occupational physicians and 11 employers, supervisors, and organization officers participated. The 222 quality of working life issues identified through the focus groups, interviews, and literature were converted into an online questionnaire. Cancer survivors (N = 20) found 44 issues not relevant or important with respect to their quality of working life. The researchers reviewed the remaining 178 issues and formulated them into 102 items classified by five categories: work perception, job characteristics, the social structure and environment, organizational characteristics, and the effect of the disease and treatment. CONCLUSIONS: The initial version of the QWLQ-CS exists out of 102 items which cover the experiences and perceptions of cancer survivors in the work environment. All items were indicated by working cancer survivors as relevant and important. IMPLICATIONS FOR CANCER SURVIVORS: This initial version of the QWLQ-CS may increase awareness of the potential problems or emotional difficulties working cancer survivors face during the work continuation process. PMID- 26370285 TI - Reference-free compression of high throughput sequencing data with a probabilistic de Bruijn graph. AB - BACKGROUND: Data volumes generated by next-generation sequencing (NGS) technologies is now a major concern for both data storage and transmission. This triggered the need for more efficient methods than general purpose compression tools, such as the widely used gzip method. RESULTS: We present a novel reference free method meant to compress data issued from high throughput sequencing technologies. Our approach, implemented in the software LEON, employs techniques derived from existing assembly principles. The method is based on a reference probabilistic de Bruijn Graph, built de novo from the set of reads and stored in a Bloom filter. Each read is encoded as a path in this graph, by memorizing an anchoring kmer and a list of bifurcations. The same probabilistic de Bruijn Graph is used to perform a lossy transformation of the quality scores, which allows to obtain higher compression rates without losing pertinent information for downstream analyses. CONCLUSIONS: LEON was run on various real sequencing datasets (whole genome, exome, RNA-seq or metagenomics). In all cases, LEON showed higher overall compression ratios than state-of-the-art compression software. On a C. elegans whole genome sequencing dataset, LEON divided the original file size by more than 20. LEON is an open source software, distributed under GNU affero GPL License, available for download at http://gatb.inria.fr/software/leon/. PMID- 26370286 TI - A comparison of Percutaneous femoral access in Endovascular Repair versus Open femoral access (PiERO): study protocol for a randomized controlled trial. AB - BACKGROUND: Access for endovascular repair of abdominal aortic aneurysms (EVAR) is obtained through surgical cutdown or percutaneously. The only devices suitable for percutaneous closure of the 20 French arteriotomies of the common femoral artery (CFA) are the Prostar(TM) and Proglide(TM) devices (Abbott Vascular). Positive effects of these devices seem to consist of a lower infection rate, and shorter operation time and hospital stay. This conclusion was published in previous reports comparing techniques in patients in two different groups (cohort or randomized). Access techniques were never compared in one and the same patient; this research simplifies comparison because patient characteristics will be similar in both groups. METHODS/DESIGN: Percutaneous access of the CFA is compared to surgical cutdown in a single patient; in EVAR surgery, access is necessary in both groins in each patient. Randomization is performed on the introduction site of the larger main device of the endoprosthesis. The contralateral device of the endoprosthesis is smaller. When we use this type of randomization, both groups will contain a similar number of main and contralateral devices. Preoperative nose cultures and perineal cultures are obtained, to compare colonization with postoperative wound cultures (in case of a surgical site infection). Furthermore, patient comfort will be considered, using VAS-scores (Visual analog scale). Punch biopsies of the groin will be harvested to retrospectively compare skin of patients who suffered a surgical site infection (SSI) to patients who did not have an SSI. DISCUSSION: The PiERO trial is a multicenter randomized controlled clinical trial designed to show the consequences of using percutaneous access in EVAR surgery and focuses on the occurrence of surgical site infections. TRIAL REGISTRATION: NTR4257 10 November 2013, NL44578.042.13. PMID- 26370287 TI - Severe early childhood caries and social determinants in three-year-old children from Northern Thailand: a birth cohort study. AB - BACKGROUND: The purpose of this study was to investigate the prevalence and social risk factors of severe early childhood caries in three-year-old children in Northern Thailand, using a birth-cohort study METHODS: The data utilized in this study were from the prospective cohort study of Thai children (PCTC) from the 28 to 38 weeks gestational age until the children reached the age of 36 months (N = 597) in Mueang Nan district, Northern Thailand. Questionnaires were administered at different time points and dental examination was conducted at the age of 3 years of the child. RESULTS: 44.1% of the 3 year old children had S-ECC. In multivariate logistic regression analysis, environmental factors (the use of rain or well water as drinking water, no schooling of mother of child, being male), and risk behaviour (sleeping with a bottle at 30 months) were associated with S-ECC. Further, in bivariate analysis, psychological distress in the mother, lack of spousal relationship support, suckle to sleep when going to bed, introduction of soft drinks at 12 months, having had more frequently sweet food, and less than daily tooth brushing before 30 months were associated with S-ECC. CONCLUSIONS: A very high rate of S-ECC was observed, and oral health may be influenced by social factors. PMID- 26370288 TI - Impact of an online writing aid tool for writing a randomized trial report: the COBWEB (Consort-based WEB tool) randomized controlled trial. AB - BACKGROUND: Incomplete reporting is a frequent waste in research. Our aim was to evaluate the impact of a writing aid tool (WAT) based on the CONSORT statement and its extension for non-pharmacologic treatments on the completeness of reporting of randomized controlled trials (RCTs). METHODS: We performed a 'split manuscript' RCT with blinded outcome assessment. Participants were masters and doctoral students in public health. They were asked to write, over a 4-hour period, the methods section of a manuscript based on a real RCT protocol, with a different protocol provided to each participant. Methods sections were divided into six different domains: 'trial design', 'randomization', 'blinding', 'participants', 'interventions', and 'outcomes'. Participants had to draft all six domains with access to the WAT for a random three of six domains. The random sequence was computer-generated and concealed. For each domain, the WAT comprised reminders of the corresponding CONSORT item(s), bullet points detailing all the key elements to be reported, and examples of good reporting. The control intervention consisted of no reminders. The primary outcome was the mean global score for completeness of reporting (scale 0-10) for all domains written with or without the WAT. RESULTS: Forty-one participants wrote 41 different manuscripts of RCT methods sections, corresponding to 246 domains (six for each of the 41 protocols). All domains were analyzed. For the primary outcome, the mean (SD) global score for completeness of reporting was higher with than without use of the WAT: 7.1 (1.2) versus 5.0 (1.6), with a mean (95 % CI) difference 2.1 (1.5 2.7; P <0.01). Completeness of reporting was significantly higher with the WAT for all domains except for blinding and outcomes. CONCLUSION: Use of the WAT could improve the completeness of manuscripts reporting the results of RCTs. TRIAL REGISTRATION: Clinicaltrials.gov ( http://clinicaltrials.gov NCT02127567 , registration date first received April 29, 2014). PMID- 26370289 TI - Long Follow-Up of Radiosurgery for Brainstem Cavernoma. AB - BACKGROUND: There is a relative paucity of long-term follow-up of treatment of brainstem cavernous angiomas. This has led to uncertainty and a lack of consensus regarding optimum therapy, especially radiosurgery. METHODS: Report of a single case with a 24-year follow-up. RESULTS: This patient was minimally symptomatic before her radiosurgery procedure. She developed an acute complication, from which she incompletely recovered. Two decades later she has become more symptomatic, with new deficits, and magnetic resonance imagings disclose progressive brainstem atrophy. CONCLUSIONS: Long-term follow-up of patients treated with radiosurgery is important. PMID- 26370290 TI - How to Improve the Attractiveness of Neurosurgery. PMID- 26370291 TI - Acute Presentation of Chiari I Malformation with Hemiparesis in a Pediatric Patient. AB - BACKGROUND: Chiari I malformation (CM-I) is defined by cerebellar tonsillar herniation through the foramen magnum. Patients typically present with chronic complaints, including headache, dizziness, and numbness, although there are few reports in the literature of pediatric patients presenting acutely with neurological deficit caused by CM-I. We report a child who presented acutely with hemiparesis and magnetic resonance imaging findings consistent with CM-I and spinal cord edema. CASE DESCRIPTION: A 3-year old boy with normal development presented with difficulty walking and increased drooling. His mother stated he was running into objects and had balance issues for several days. Neurological examination showed ataxia with falling to the right after a few steps and weakness of the right arm and leg. His medical history was remarkable only for mild asthma, although he had recently been treated for an upper respiratory viral infection. Computed tomography of the head demonstrated no brainstem mass. Magnetic resonance imaging of the head and cervical spine showed tonsillar ectopia approximately 2 cm below the craniocervical junction with increased T2 signal in the spinal cord from C1 to C3 consistent with syringomyelia and cord edema. The patient underwent suboccipital craniectomy with removal of the posterior arch of C1 and dural patch graft. His postoperative course was unremarkable, with complete resolution of his symptoms at his 1-month follow-up visit. CONCLUSIONS: This case highlights an unusual presentation of CM-I with neurological deficit related to spinal cord edema, possibly precipitated by the "water-hammer" effect of this patient's coughing fits. Providers should be aware of the acute presentations of CM-I. PMID- 26370292 TI - Problem behaviour and traumatic dental injuries in adolescents. AB - AIM: To explore the relationship between problem behaviour and traumatic dental injuries (TDI) among 15- to 16-year-old schoolchildren from East London. METHODS: This cross-sectional study used data from 794 adolescents who participated in phase III of the Research with East London Adolescents Community Health Survey (RELACHS), a school-based prospective study of a representative sample of adolescents. Participants completed a questionnaire and were clinically examined for TDI, overjet and lip coverage. The Strength and Difficulties Questionnaire (SDQ) was used to assess problem behaviour, which provided a total score and five domain scores (emotional symptoms, conduct problems, hyperactivity, peer problems and pro-social behaviour). The association between problem behaviour and TDI was assessed in unadjusted and adjusted logistic regression models. Adjusted models controlled for demographic (sex, age and ethnicity), socio-economic (parental employment) and clinical factors (overjet and lip coverage). RESULTS: The prevalence of TDI was 17% and the prevalence of problem behaviour, according to the SDQ, was 10%. In the adjusted model, adolescents with problem behaviour were 1.87 (95% confidence interval: 1.03-3.37) times more likely to have TDI than those without problem behaviour. In subsequent analysis by SDQ domains, it was found that only peer problems were associated with TDI (OR = 1.78, 95% CI: 1.01 3.14), even after adjustment for confounders. CONCLUSION: This study found evidence for a relationship between problem behaviour and TDI among adolescents, which was mainly due to peer relationship problems. PMID- 26370293 TI - A novel myxozoan parasite of terrestrial mammals: description of Soricimyxum minuti sp. n. (Myxosporea) in pygmy shrew Sorex minutus from Hungary. AB - As part of a biodiversity study in northwestern Hungary, we conducted a parasitological survey of small mammals. In both common shrews (Sorex araneus Linnaeus) and pygmy shrews (Sorex minutus Linnaeus), we found myxospores of a species of Soricimyxum Prunescu, Prunescu, Pucek et Lom, 2007 (Myxosporea) and plasmodia in the bile ducts within the liver. Spores from both species of shrewswere morphologically and morphometrically indistinguishable, but differed in their SSU rRNA gene sequences by 3.3%. We identified spores and developmental stages from the common shrew as Soricimyxum fegati Prunescu, Prunescu, Pucek et Lom, 2007, based on morphometric data and DNA sequence similarity. Spores from the pygmy shrew were only 96.7% similar to S. fegati, hence we identified them as a novel myxosporean Soricimyxum minuti sp. n. This is only the second myxosporean parasite species described from mammals. PMID- 26370294 TI - Functional protein aggregates: just the tip of the iceberg. AB - An increasing number of both prokaryotic and eukaryotic cell types are being adapted as platforms for recombinant protein production. The overproduction of proteins in such expression systems leads to the formation of insoluble protein based aggregates. Although these protein clusters have been poorly studied in most of the eukaryotic systems, aggregates formed in E. coli, named inclusion bodies (IBs), have been deeply characterized in the last decades. Contrary to the general belief, an important fraction of the protein embedded in IB is functional, showing promise in biocatalysis, regenerative medicine and cell therapy. Thus, the exploration of all these functional protein clusters would largely expand their potential in both pharma and biotech industry. PMID- 26370295 TI - Effect of post-treatment conditions on the inactivation of helminth eggs (Ascaris suum) after the composting process. AB - Safe and appropriate disposal of human waste is a basic requirement for sanitation and protection of public health. For proper sanitation and nutrient recovery, it is necessary to ensure effective treatment methods to complete pathogen destruction in excreta prior to reuse. Composting toilets convert faeces to a reusable resource such as fertilizer or humus for organic agriculture. A composting toilet for rural Burkina Faso was created by modifying a commercial model available in Japan to improve hygiene and increase food production. The toilet has shown to result in a degraded final product, but its effectiveness for pathogen destruction was unclear due to low temperatures generated from the toilet. This study aimed to sanitize compost withdrawn from the composting toilet for food production by setting post-treatment conditions. The inactivation kinetics of Ascaris suum eggs, selected as an indicator for helminth eggs, was determined during post-treatment at different temperatures (30 degrees C, 40 degrees C, 50 degrees C and 60 degrees C) with varying moisture contents (MC) (50%, 60% and 70%). The treatment of compost in a possible additional post treatment after the composting process was tried in the laboratory test. Inactivation of A. suum eggs was fast with greater than two log reductions achieved within 2 h for temperature 50 degrees C and 50% MC and greater than three log reductions for temperature 60 degrees C and 50% MC within 3 h. Statistical analysis showed the significant impact of temperature and moisture on the inactivation rates of A. suum eggs. The post-treatment can efficiently increase helminth eggs destruction prior to reuse. PMID- 26370296 TI - A successful pregnancy and parturition in a patient with anuria undergoing maintenance hemodialysis for 6 years: a case report of a 3-year-follow-up. AB - BACKGROUND: Pregnancies in hemodialysis patients are uncommon and difficult to study. Although the chance of a successful pregnancy and parturition in hemodialysis women has increased over the years, it still remains extremely low with a high maternal and fetal mortality and morbidity rate. CASE PRESENTATION: We reported a case of successful pregnancy and parturition in a 22-year-old Chinese female in uremic stage of chronic renal failure and undergoing maintenance hemodialysis (three sessions a week) for 6 years. At the 22nd gestational week, she was diagnosed as pregnant by ultrasound, and started an enhanced hemodialysis routine (Five sessions a week). At the 32nd gestational week, she got hospitalized and received hemodialysis more frequently (seven sessions a week). Based on the initial diagnoses, including uremic stage of chronic renal failure, stage-3 hypertension, single pregnancy of 32nd gestational week, single umbilical artery and polyhydramnios, a drug therapy consisting of compound amino acid, fructosediphosphate sodium, 10% L-carnitine, erythropoietin, polyferose, amlodipine, isosorbidedinitrate, low-molecular weight-heparin, multivitamins and folic acid was given, and daily examination of the mother and fetus was performed. Under the joint efforts of various departments, the patient underwent caesarean section at the 34th gestational week due to progressive uterine contraction and gave birth to a female, well-being baby weighing 1470 g. It has been more than 3 years since the parturition. The mother has returned to the previous hemodialysis routine, and the child has been growing up healthily. CONCLUSION: Although pregnancy in hemodialysis patients is rare, with a high rate of risks. Patients could still gain a good outcome, if we intensify hemodialysis and enhance the collaboration between the patient, nephrologists, obstetricians, neonatologist, nutritionists, and other departments. PMID- 26370298 TI - Surgeon fails in attempt to get patients' inquest verdict changed. PMID- 26370297 TI - Mobility dynamics of migrant workers and their socio-behavioral parameters related to malaria in Tier II, Artemisinin Resistance Containment Zone, Myanmar. AB - BACKGROUND: Areas with dynamic population movements are likely to be associated with higher levels of drug-resistant malaria. Myanmar Artemisinin Resistance Containment (MARC) Project has been launching since 2012. One of its components includes enhancing strategic approaches for mobile/migrant populations. We aimed to ascertain the estimated population of mobile migrant workers and their families in terms of stability in work setting in townships classified as tier II (areas with significant inflows of people from areas with credible evidence of artemisinin resistance) for Artemisinin resistance; to identify knowledge, attitudes and practices related to prevention and control of malaria and to recommend cost-effective strategies in planning for prevention and control of malaria. METHODS: A prospective cross-sectional study conducted between June to December 2013 that covered 1,899 migrant groups from 16 tier II townships of Bago Region, and Kayin and Kayah States. Trained data collectors used a pre-tested and subsequently modified questionnaire and interviewed 2,381 respondents. Data of migrant groups were analyzed and compared by category depending upon the stability of their work setting. RESULTS: The estimated population of the 1,899 migrant groups categorized into three on the nature of their work setting was 56,030. Bago region was the commonest reported source of origin of migrant groups as well as their transit. Malaria volunteers were mostly within the reach of category 1 migrant groups (43/66, 65.2 %). Less stable migrant groups in category 3 had limited access to malaria information (14.7 %) and malaria care providers (22.1 %), low level of awareness and use of long-lasting insecticide-treated nets (46.6 and 38.8 %). Also, they had poor knowledge on malaria prevention on confirming suspected malaria and on using artemisinin combined therapy (ACT). Within two weeks prior to the survey, only 16.5 % of respondents in all categories combined reported acute undifferentiated fever. DISCUSSION AND CONCLUSIONS: Mobility dynamics of migrant groups was complex and increased their vulnerability to malaria. This phenomenon was accentuated in less stable areas. Even though migrant workers were familiar with rapid diagnostic tests for malaria, ACT still needed wide recognition to improve practices supportive of MARC including the use of appropriate personal protection. High mobility calls for re-designation of tier II townships to optimize ACT resistance containment. PMID- 26370299 TI - Patients aged over 75 years enrolled in Phase I clinical trials: the Gustave Roussy experience. AB - Although a third of all cancers are diagnosed after the age of 75, only 9% of elderly people are recruited in clinical trials, because of fear of the risk of toxicity. The aim of this study was to compare the tolerance and efficacy observed in Phase I trials among patients aged over 75 years with that observed in younger patients. Patients treated from 2007 to 2012 at Institut Gustave Roussy in Phase I trials were included. The conditional Cox proportional hazards model was used to compare the occurrence of AE and overall survival in a subpopulation of elderly people (EP, aged >75 years) matched with patients aged <75 years (YP) according to the same Phase I protocol and the same Royal Marsden Hospital (RMH) prognostic score. Among the 32 EP and the 158 YP, 63% and 61% experienced Grade 3-4 AEs and dose-limiting toxicities occurred in 6% and 11% in each group respectively. Age over 75 years was neither associated with a greater risk of high toxicity (HR=0.90 [CI95%, 0.47-1.70], p = 0.74) nor of death (HR=0.86; CI95%: 0.38-1.93; p = 0.71). Age over 75 years had no impact on the occurrence of either high toxicity or of death. PMID- 26370300 TI - PEG spacer gel and adaptive planning vs single plan in external prostate radiotherapy--clinical dosimetry evaluation. AB - OBJECTIVE: Spacer gel is used to reduce the rectal dose in prostate radiotherapy. It is injected to increase the distance between the prostate and rectum. During the course of external radiotherapy treatment, physiological changes in rectal volume exist. When using polyethylene glycol material, such as DuraSeal((r)) (Covidien, Mansfield, MA), gel resorption also occurs. Together, these factors alter the original dose plan distribution. METHODS: External dose planning and calculations were simulated using images acquired from 10 patients who were treated with brachytherapy and gel. The CT series was taken relative to gel injection: pre 1 day, post 1 day, post 1 month and post 2 months. Adaptive planning was compared with a single plan. RESULTS: Adaptive planning shows better results compared with the single plan used in the total treatment course; however, the effect is minor. CONCLUSION: Gel usage is clearly favourable to rectal DVH. Using adaptive planning with gel improves rectal DVH but is not necessary according to this study. ADVANCES IN KNOWLEDGE: Spacer gel is used in prostate radiotherapy to increase distance between the prostate and the rectum, thus reducing the rectal doses. During the treatment course, gel resorption exists which affects the rectal doses. The usefulness of adaptive planning to compensate this resorption effect has not been studied before. PMID- 26370301 TI - The updated incidences and mortalities of major cancers in China, 2011. AB - INTRODUCTION: The National Central Cancer Registry (NCCR) of China collected population-based cancer registration data from all cancer registries in China. This study aimed to compile national cancer incidences and mortalities in 2011 and estimate cancer incident new cases and cancer deaths. METHODS: In 2014, there were 234 cancer registries that submitted records of new cancer cases and cancer deaths that occurred in 2011 to the NCCR. All datasets were evaluated based on the criteria of data quality of the NCCR. The data of 177 registries was of sufficient quality and was compiled to evaluate cancer statistics in 2011. The pooled data were stratified by area, sex, age group, and cancer type. Cancer incident cases and deaths were estimated using age-standardized rates (ASR) and the Chinese population. All incidences and mortalities were age-standardized to the 2000 Chinese standard population and Segi's population. RESULTS: The estimates of new cancer incident cases and cancer deaths were 3,372,175 and 2,113,048 in 2011, respectively. The crude incidence was 250.28/1,00,000 (277.77/1,00,000 for males and 221.37/1,00,000 for females). The ASRs of incidence by the Chinese standard population (ASRIC) and by the world standard population (ASRIW) were 186.34/1,00,000 and 182.76/1,00,000, respectively, with a cumulative incidence (0-74 years old) of 21.20%. Cancers of the lung, female breast, stomach, liver, colorectum, esophagus, cervix, uterus, prostate, and ovary were the most common cancers, accounting for approximately 75% of all new cancer cases. Lung, liver, gastric, esophageal, colorectal, female breast, pancreatic, brain, and cervical cancers and leukemia were the leading causes of cancer death, accounting for approximately 80% of all cancer deaths. Cancer incidence, mortality, and spectrum were all different between urban and rural areas and between males and females. CONCLUSIONS: The population covered by the cancer registries greatly increased from 2010 to 2011. The data quality and representativeness of cancer registries have gradually improved. Cancer registries have an irreplaceable role in research on cancer prevention and control. The disease burden of cancer is increasing, and the health department must implement effective measures to contain the increased cancer burden in China. PMID- 26370302 TI - Organotemplate-free synthesis of two open-framework metal borophosphates. AB - Two new isostructural metal borophosphates, |K2(H2O)|[CoB2P3O12(OH)] [M = Co (1), Ni (2)], have been hydrothermally synthesized with non-polluting K(+) ions instead of organic template-ethylenediamine. The two metal borophosphates are isostructural and constructed by the connection of tetrahedral layers and MO6 octahedra, giving rise to the 3-D intersecting 8-ring channels along the [010] direction. The negative charge of the framework is compensated by the K(+) ions located in the 8-ring channels. Like ethylenediamine, the K(+) ions also play an important structural directing role in the formation of the open framework. The framework shows a high thermal stability and is stable upon calcination at ca. 400 and 500 degrees C for 1 and 2, respectively. Considering the motion of K(+) ions, ionic conductivities of the two compounds were performed. The results indicated that they have similar activation energies of 0.94-1.09 eV and conductivities of 6.76 * 10(-8)-9.88 * 10(-8) S cm(-1) at 320 degrees C. PMID- 26370303 TI - Ultraviolet Radiation-Elicited Enhancement of Isoflavonoid Accumulation, Biosynthetic Gene Expression, and Antioxidant Activity in Astragalus membranaceus Hairy Root Cultures. AB - In this work, Astragalus membranaceus hairy root cultures (AMHRCs) were exposed to ultraviolet radiation (UV-A, UV-B, and UV-C) for promoting isoflavonoid accumulation. The optimum enhancement for isoflavonoid production was achieved in 34-day-old AMHRCs elicited by 86.4 kJ/m(2) of UV-B. The resulting isoflavonoid yield was 533.54 +/- 13.61 MUg/g dry weight (DW), which was 2.29-fold higher relative to control (232.93 +/- 3.08 MUg/g DW). UV-B up-regulated the transcriptional expressions of all investigated genes involved in isoflavonoid biosynthetic pathway. PAL and C4H were found to be two potential key genes that controlled isoflavonoid biosynthesis. Moreover, a significant increase was noted in antioxidant activity of extracts from UV-B-elicited AMHRCs (IC50 values = 0.85 and 1.08 mg/mL) in comparison with control (1.38 and 1.71 mg/mL). Overall, this study offered a feasible elicitation strategy to enhance isoflavonoid accumulation in AMHRCs and also provided a basis for metabolic engineering of isoflavonoid biosynthesis in the future. PMID- 26370304 TI - Nanomechanical clues from morphologically normal cervical squamous cells could improve cervical cancer screening. AB - Applying an atomic force microscope, we performed a nanomechanical analysis of morphologically normal cervical squamous cells (MNSCs) which are commonly used in cervical screening. Results showed that nanomechanical parameters of MNSCs correlate well with cervical malignancy, and may have potential in cancer screening to provide early diagnosis. PMID- 26370305 TI - An RNA-based approach to sequence the mitogenome of Hypoptopoma incognitum (Siluriformes: Loricariidae). AB - Hypoptopoma incognitum is a fish of the fifth most species-rich family of vertebrates and abundant in rivers from the Brazilian Amazon. Only two species of Loricariidae fish have their complete mitogenomes sequence deposited in the Genbank. An innovative RNA-based approach was used to assemble the complete mitogenome of H. incognitum with an average coverage depth of 5292*. The typical vertebrate mitochondrial features were found; 22 tRNA genes, two rRNA genes, 13 protein-coding genes, and a non-coding control region. Moreover, the use of this approach allowed the measurement of mtRNA expression levels, the punctuation pattern of editing, and the detection of heteroplasmies. PMID- 26370306 TI - Ruptured spinal artery aneurysm associated with coarctation of the aorta. PMID- 26370307 TI - Slowly progressive solitary plasmacytoma of the thoracic spine. PMID- 26370308 TI - Long term stability of HBsAg, anti-HBc and anti-HCV in dried blood spot samples and eluates. AB - BACKGROUND: Dried blood spots (DBS) are a useful specimen collection tool in situations where venous access is problematic, however, detection of biomarkers from this specimen type is subject to variation depending on storage conditions and storage time. OBJECTIVES: The objective of this study is to assess the detection of HBsAg, anti-HBc and anti-HCV from DBS after storage. STUDY DESIGN: DBS specimens were stored at -70 degrees C, -20 degrees C, 4 degrees C, 22 to 28 degrees C and 37 degrees C either with or without desiccant. Eluates were also prepared from DBS specimens and stored at -20 degrees C and -70 degrees C. DBS cards and eluates were tested for HBsAg, anti-HBc and anti-HCV at baseline on day 0 and thereafter at intervals of 14, 70 and 200 days. RESULTS: Loss of detection of both HBsAg and anti-HBc was evident by the first time point (14 days) in all storage conditions except for the samples (DBS and eluates) stored at -20 degrees C or -70 degrees C. Both HBsAg and anti-HBc stored under these conditions showed minimal variation up to the final time point (200 days) of storage. The detection of anti-HCV did not differ between the 22 to 28 degrees C, 4 degrees C, -20 degrees C and -70 degrees C DBS nor the -20 degrees C or the -70 degrees C stored eluates over the 200 day time period. CONCLUSION: We suggest that extended storage of DBS intended for downstream testing is best carried out by freezing either the DBS, or eluate, at -20 degrees C or -70 degrees C as soon as possible following collection for optimal detection of HBsAg, anti-HBc and anti-HCV. PMID- 26370309 TI - Long-term follow-up for incident cirrhosis among pediatric cancer survivors with hepatitis C virus infection. AB - BACKGROUND: Pediatric cancer patients who received blood transfusions were potentially exposed to hepatitis C virus (HCV) prior to second-generation HCV screening of blood products in 1992. Limited evidence is available about long term incident cirrhosis in this population. OBJECTIVES: We aimed to estimate the overall and sex-specific incidence of cirrhosis among HCV-seropositive survivors of pediatric cancer. STUDY DESIGN: We identified 113HCV-seropositive pediatric cancer patients treated at St. Jude Children's Research Hospital between 1962 and 1997, who survived >=5 years post-diagnosis, and were followed through 2014. Our outcome was cirrhosis determined by liver biopsy or diagnostic imaging. We used a competing-risk framework to estimate the overall and sex-specific cumulative incidence and 95% confidence limits (CL) of cirrhosis at 10-year follow-up intervals. RESULTS: The median duration of follow-up was 30 years (interquartile range=28-36) post-cancer diagnosis. Cumulative incidence of cirrhosis increased at each 10-year interval from 0% after 10 years to 13% after 40 years (Ptrend<0.001). The median age at diagnosis of cirrhosis was 30 years (interquartile range=24-38). We observed a linear trend in incidence for males (Ptrend<0.001), with a cumulative incidence of 18% (95% CL: 6.1%, 34%) after 40 years. The cumulative incidence for females was 6.5% (95% CL: 0.42%, 26%) after 40 years, but we did not observe a linear trend (Ptrend=0.99). CONCLUSION: Our results suggest that the incidence of cirrhosis is similar between HCV seropositive pediatric cancer survivors and the general population given similar duration of follow-up, but survivors may be diagnosed with cirrhosis at an earlier age. PMID- 26370310 TI - Low frequency of acute hepatitis E virus (HEV) infections but high past HEV exposure in subjects from Cambodia with mild liver enzyme elevations, unexplained fever or immunodeficiency due to HIV-1 infection. AB - BACKGROUND: In Cambodia, previous studies conducted on hepatitis E virus (HEV) infection are scant, sometimes old, and showed inconsistent results. Moreover, there is no data about HEV infection in Cambodian HIV-1-infected patients. OBJECTIVES: To assess the occurrence of acute HEV infections and the level of past HEV exposure in one Mekong country. STUDY DESIGN: Using anti-HEV IgM and HEV RNA detection, we retrospectively investigated the presence of acute HEV infection in 825 individuals, including 350 subjects with or without fever, 300 subjects with or without liver enzyme elevations (LEE) and 175 antiretroviral treatment (ART)-naive, severely immunocompromised HIV-1-infected patients. The detection of anti-HEV IgG was also performed to assess ancient HEV exposure. RESULTS: Nine individuals tested positive for anti-HEV IgM yielding an overall rate of 1.1% (95% confidence interval (CI), 0.5-2.0). We did not find significant differences for anti-HEV IgM rates between subjects with unexplained fevers (1.5%) and those with malaria or dengue-associated fever (1.7%) or non-febrile individuals (0%) (P=0.49), and between subjects with (1.5%) and without (2.0%) LEE (P=0.87). No HIV-infected patient tested positive for anti-HEV IgM. HEV RNA was not detected in all tested plasma specimens (n=578). Overall, the anti-HEV IgG prevalence rate was 30.1% (95% CI, 27.0-33.2). CONCLUSIONS: The scarcity of recent HEV infection contrasted with the high level of past HEV exposure. The role of HEV in liver disease is likely minor in Cambodia since no HEV RNA was detected in our studied populations, including HIV-positive patients with severe immunodepression. PMID- 26370311 TI - Optimizing JC and BK polyomavirus IgG testing for seroepidemiology and patient counseling. AB - BACKGROUND: Polyomavirus JC (JCPyV) and BK (BKPyV) can cause significant diseases in immunocompromised patients including nephropathy, hemorrhagic cystitis, and leukoencephalopathy. Recently, JCPyV and BKPyV IgG have been explored as risk predictors in multiple sclerosis and transplant patients, but sensitivity, specificity and quantification issues limit current performance. OBJECTIVE: To improve JCPyV and BKPyV-specific antibody testing. STUDY DESIGN: Healthy blood donor sera (N=400) were tested at dilutions 1:100, 1:200, and 1:400 for JCPyV- and BKPyV-specific IgG using VP1 virus-like particle (VLP)-based ELISAs normalized to a laboratory reference serum. Normalized optical density 492nm greater or equal 0.1 in all 3 dilutions was regarded as reactive. Sera with discordant reactivity in at least one dilution were retested after VLP preadsorption. RESULTS: At dilutions 1:100, 1:200, and 1:400, IgG reactivity was 74%, 60% and 53% for JCPyV, and 93%, 86% and 74% for BKPyV, respectively. At these dilutions, JCPyV-VLP preadsorption identified 56, 4 and 0 false-positives and 0, 4 and 27 false-negatives, respectively. Dilution-dependent sensitivity was 100%, 98%, and 89%, and specificity 65, 98%, and 100%, respectively. For sera diluted 100-, 200-, and 400-fold, BKPyV-VLP preadsorption identified 28, 1 and 0 false-positives, and 0, 0 and 46 false-negatives, and sensitivity was 100%, 100%, 86%, and specificity 50%, 98%, 100%, respectively. CONCLUSION: For seroepidemiology studies, normalized JCPyV and BKPyV IgG ELISA at 1:200 serum dilution provides optimal sensitivity and specificity with the lowest false positive and false-negative rate. For individual risk assessment, dilutions of 100, 200, and 400 combined with preadsorption for low-reactive sera may be most appropriate. PMID- 26370312 TI - Human papillomavirus DNA in pharyngeal scrapes as a marker of HPV-related squamous cell cancer of the oropharynx. AB - BACKGROUND: Recent studies have indicated that human papillomavirus is an etiologic agent for a subset of head and neck cancers associated with better prognosis, therefore, prompt confirmation of such etiology seems to be crucial for choosing the optimal therapeutic option. Standard HPV diagnosis is currently based on histopathological material. In the present study, the novel diagnostic method based on pharyngeal brush biopsy is proposed. OBJECTIVES: The aim of this study was to evaluate the usefulness of the Real-Time PCR-based (RT-PCR) test in detecting HPV-related cancer of the oropharynx using superficial scraps taken from the oropharyngeal region. STUDY DESIGN: Ninety patients with head and neck squamous cell cancer were enrolled in the study. The presence of HPV DNA in pharyngeal superficial scrapes assessed by RT-PCR was compared to the HPV status in the tumor tissue samples determined by a combined RT-PCR/P16(INK4A) expression algorithm. Analytical sensitivity and specificity were calculated and the clinical outcome was analyzed in correlation to the HPV status. RESULTS: HR-HPV DNA in pharyngeal swabs was revealed in 25 cases (28.4%) and simultaneously confirmed in all corresponding tissue samples. Sensitivity and specificity of the viral status assessment in the brush biopsies in respect to the RT-PCR/P16(INK4A) 20 were 100% and 96.2%, respectively. HR-HPV positive status was associated with an excellent clinical outcome and reduced hazard ratio of recurrence and disease related death. CONCLUSIONS: The proposed novel method of HPV status assessment using RT-PCR and superficial scraps appeared to be highly sensitive, specific, and useful in predicting the clinical outcome. PMID- 26370313 TI - Detection and characterization of enteroviruses and parechoviruses in healthy people living in the South of Cote d'Ivoire. AB - BACKGROUND: Human enteroviruses (EVs) and parechoviruses (HPeVs) belong to the family Picornaviridae. Although most EV and HPeV infections remain asymptomatic, both pathogens can cause a wide spectrum of clinical manifestations ranging from respiratory or gastrointestinal symptoms to myocarditis, neonatal sepsis, and infections of the central nervous system. OBJECTIVES: Aim of the present study was to investigate the spectrum of EVs and HPeVs in apparently healthy adults and children living in the South of Cote d'Ivoire. STUDY DESIGN: The study included 105 stool samples obtained from healthy individuals aged 0-53 years between June 2013 and December 2014 in the Sud-Como region of Cote d'Ivoire. After collection and shipment to Germany, the samples were analyzed by real-time PCR for the presence of EVs and HPeVs RNA. Molecular typing and virus isolation of all samples were performed.''e RESULTS: Out of 105 samples, 24 (22.8%) were EV positive and six (5.2%) were HPeV positive. Twenty-one EV positive samples could be characterized with serotypes belonging to EV group A-C, while three could not be further specified. Interestingly, several rarely described serotypes were identified, e.g., EV-C99, EV-B93, EV-C116, and EV-A119. Typing of HPeV positive samples resulted in HPeV-1 and -5 detections, while one isolate could not be assigned to the known HPeV types. CONCLUSIONS: This study showed a large variety of EV strains in healthy people in the South of Cote d'Ivoire and provided the first available data about HPeV infections in a sub-Saharan African country. PMID- 26370314 TI - A comparison of H1N1 influenza among pediatric inpatients in the pandemic and post pandemic era. AB - BACKGROUND: The novel influenza A H1N1 (A[H1N1]pdm09) strain emerged in 2009, contributing to significant morbidity and mortality. It is not known whether illness associated with A(H1N1) pdm09 in the post-pandemic era exhibits a similar disease profile. OBJECTIVE: The objectives of this study were to compare the burden of disease of A(H1N1) pdm09 influenza from the 2009 pandemic year to the post-pandemic years (2010-2014), and to explore potential reasons for any differences. STUDY DESIGN: We conducted a retrospective cohort study of inpatients admitted to Children's Hospital Colorado with a positive respiratory specimen for influenza from May-December, 2009 and December, 2010-April, 2014. Univariate and multivariate analyses were conducted to compare the demographics and clinical characteristics of patients with H1N1 during the two periods. RESULTS: There were 388 inpatients with influenza A(H1N1) pdm09 in 2009, and 117 during the post-pandemic years. Ninety-four percent of all H1N1 during the post pandemic era was observed during the 2013-2014 influenza season. Patients with A(H1N1) pdm09 during the post-pandemic year were less likely to have an underlying medical condition (P<0.01). Patients admitted to the ICU during the post-pandemic year had a lower median age (5 vs 8 years, P=0.01) and a lower proportion of patients were intubated, had mental status changes, and ARDS compared with the pandemic years, (P<0.01 for all), with decreased mortality (P=0.02). CONCLUSION: Patients with influenza A(H1N1) pdm09 during the post pandemic years appeared to have less severe disease than patients with A(H1N1) pdm09 during the pandemic year. The reasons for this difference are likely multifactorial. PMID- 26370315 TI - Clinical and molecular epidemiology of human rhinovirus infections in patients with hematologic malignancy. AB - BACKGROUND: Human rhinoviruses (HRVs) are common causes of upper respiratory tract infection (URTI) in hematologic malignancy (HM) patients. Predictors of lower respiratory tract infection (LRTI) including the impact of HRV species and types are poorly understood. OBJECTIVES: This study aims to describe the clinical and molecular epidemiology of HRV infections among HM patients. STUDY DESIGN: From April 2012-March 2013, HRV-positive respiratory specimens from symptomatic HM patients were molecularly characterized by analysis of partial viral protein 1 (VP1) or VP4 gene sequence. HRV LRTI risk-factors and outcomes were analyzed using multivariable logistic regression. RESULTS: One hundred and ten HM patients presented with HRV URTI (n=78) and HRV LRTI (n=32). Hypoalbuminemia (OR 3.0; 95% CI, 1.0-9.2; p=0.05) was independently associated with LRTI, but other clinical and laboratory markers of host immunity did not differ between patients with URTI versus LRTI. Detection of bacterial co-pathogens was common in LRTI cases (25%). Among 92 typeable respiratory specimens, there were 58 (64%) HRV-As, 12 (13%) HRV Bs, and 21 (23%) HRV-Cs, and one Enterovirus 68. LRTI rates among HRV-A (29%), HRV-B (17%), and HRV-C (29%) were similar. HRV-A infections occurred year-round while HRV-B and HRV-C infections clustered in the late fall and winter. CONCLUSIONS: HRVs are associated with LRTI in HM patients. Illness severity is not attributable to specific HRV species or types. The frequent detection of bacterial co-pathogens in HRV LRTIs further substantiates the hypothesis that HRVs predispose to bacterial superinfection of the lower airways, similar to that of other community-acquired respiratory viruses. PMID- 26370316 TI - Altered Plasma MicroRNAs as Novel Biomarkers for Arteriosclerosis Obliterans. AB - AIM: Arteriosclerosis obliterans (ASO) of the lower extremities is a major cause of adult limb loss worldwide. A timely diagnosis in the early stages of the disease determines the clinical outcomes, however lacking of palpable symptoms remains the biggest obstacle. This study aimed to screen a cluster of microRNAs (miRNAs) that can be used as biomarker for the ASO in the earlier stages. METHODS: Plasma from 3 patients with ASO and 3 healthy controls were profiled to screen altered miRNAs by microarray, then Real time PCR was further used to confirm the changes in 55 ASO patients and 54 controls.We also analyzed the correlation of miRNAs level with Fontaine stages and the influence of T2DM which is a common complication with ASO on the level of miRNAs. RESULT: Twenty-four aberrantly expressed miRNAs were screened in the plasma of ASO patients. Real time PCR verified that the level of miR-4284 was significantly increased, while levels of miR-4463, miR-4306 and miR-221-3p were significantly decreased both in the plasma and in the sclerotic samples compared with the controls. Interestingly, we revealed a time and stage specific expression manner, as shown that expression of miR-4284 increased at the stage I of ASO and maintained the tendency to stage IV, while miR-4463 expression decreased at every stage of ASO; however, the expression of miR-4463 showed opposite changes in ASO patients with or without T2DM. CONCLUSION: Altered expressions of miR-4284 and miR-4463 are novel characteristics and may serve as potential biomarkers for the early diagnosis of ASO. PMID- 26370317 TI - Combination of Invasive and Non-Invasive Vascular Examinations: Usefulness from the Preemptive Aspect. PMID- 26370319 TI - Noradrenaline-mediated facilitation of inhibitory synaptic transmission in the dorsal horn of the rat spinal cord involves interlaminar communications. AB - In the dorsal horn of the spinal cord (DH), noradrenaline (NA) is released by axons originating from the locus coeruleus and induces spinal analgesia, the mechanisms of which are poorly understood. Here, the effects of NA on synaptic transmission in the deep laminae (III-V) of the DH were characterized. It was shown that exogenously applied, as well as endogenously released, NA facilitated inhibitory [gamma-aminobutyric acid (GABA)ergic and glycinergic] synaptic transmission in laminae III-IV of the DH by activating alpha1-, alpha2- and beta adrenoceptors (ARs). In contrast, NA had no effect on excitatory (glutamatergic) synaptic transmission. Physical interruption of communications between deep and more superficial laminae (by a mechanical transection between laminae IV and V) totally blocked the effects of alpha2-AR agonists and strongly reduced the effects of alpha1-AR agonists on inhibitory synaptic transmission in laminae III IV without directly impairing synaptic release of GABA or glycine from neurons. Short-term pretreatment of intact spinal cord slices with the glial cell metabolism inhibitor fluorocitrate or pharmacological blockade of ionotropic glutamate and ATP receptors mimicked the consequences of a mechanical transection between laminae IV and V. Taken together, the current results indicate that the facilitation of inhibitory synaptic transmission in laminae III-IV of the DH by NA requires functional interlaminar connections between deep and more superficial laminae, and might strongly depend on glia to neuron interactions. These interlaminar connections and glia to neuron interactions could represent interesting targets for analgesic strategies. PMID- 26370318 TI - High yield exogenous protein HPL production in the Bombyx mori silk gland provides novel insight into recombinant expression systems. AB - The silk gland of Bombyx mori (BmSG) has gained significant attention by dint of superior synthesis and secretion of proteins. However, the application of BmSG bioreactor is still a controversial issue because of low yields of recombinant proteins. Here, a 3057 bp full-length coding sequence of Hpl was designed and transformed into the silkworm genome, and then the mutant (Hpl/Hpl) with specific expression of Hpl in posterior BmSG (BmPSG) was obtained. In the mutants, the transcription level of Fib-L and P25, and corresponding encoding proteins, did not decrease. However, the mRNA level of Fib-H was reduced by 71.1%, and Fib-H protein in the secreted fibroin was decreased from 91.86% to 71.01%. The mRNA level of Hpl was 0.73% and 0.74% of Fib-H and Fib-L, respectively, while HPL protein accounted for 18.85% of fibroin and 15.46% of the total amount of secreted silk protein. The exogenous protein was therefore very efficiently translated and secreted. Further analysis of differentially expressed gene (DEG) was carried out in the BmPSG cells and 891 DEGs were detected, of which 208 genes were related to protein metabolism. Reduced expression of endogenous silk proteins in the BmPSG could effectively improve the production efficiency of recombinant exogenous proteins. PMID- 26370320 TI - Ultrasound-targeted microbubble destruction-mediated downregulation of CD133 inhibits epithelial-mesenchymal transition, stemness and migratory ability of liver cancer stem cells. AB - Hepatocellular carcinoma (HCC) is an aggressive disease with a poor outcome due to the high incidence of metastasis. Cancer stem cells (CSCs) have been identified to be responsible for tumor progression and may be generated by epithelial-mesenchymal transition (EMT) characteristics. CD133 is a specific surface marker for liver cancer stem cells (LCSCs), which is also considered as an important functional factor for tumorigenesis and overall survival in HCC. Ultrasound-targeted microbubble destruction (UTMD) has recently been used as a novel, safe and effective gene transfection technology. The aim of the present study was to elucidate the regulatory mechanism of CD133 and EMT in LCSCs and whether the UTMD-based shRNA delivery system facilitated gene delivery in LCSCs. In the present study, CD133+ cells were isolated from the SMMC-7721 HCC cell line and then transfected with shCD133 mediated by UTMD and liposomes, respectively. Compared to the liposomes group, the UTMD group resulted in significantly improved transfection efficiency. The downregulation of CD133 reversed the EMT program, attenuated self-renewal, proliferation and migration of CD133+ LCSCs and suppressed the growth of CSC tumor xenografts. Additionally, the downregulation of CD133 led to downregulation of the nuclear factor-kappaB (NF-kappaB) pathway. The present study demonstrated that CD133 plays a critical role in the regulation of the EMT process, tumor-initiating properties and migratory ability of LCSCs. The UTMD technique targeted for CD133 downregulation may be examined as a potential therapeutic strategy for HCC. PMID- 26370321 TI - The impact of biologic therapy in chronic plaque psoriasis from a societal perspective: an analysis based on Italian actual clinical practice. AB - OBJECTIVE: Psoriasis is one of the most common forms of chronic dermatitis, affecting 2-3% of the worldwide population. It has a serious effect on the way patients perceive themselves and others, thereby prejudicing their quality of life and giving rise to a significant deterioration in their psycho-physical well being; it also poses greater difficulties for them in leading a normal social life, including their ability to conduct a normal working life. All the above mentioned issues imply a cost for the society. This study proposes to evaluate the impact on societal costs for the treatment of chronic plaque psoriasis with biologics (etanercept, infliximab and adalimumab) in the Italian clinical practice. METHOD: A prospective observational study has been conducted in 12 specialized centres of the Psocare network, located throughout Italy. Direct and indirect costs (as well as the health-related quality of life of patients with plaque psoriasis undergoing biologic treatments) have been estimated, while the societal impact has been determined using a cost-utility approach. RESULTS: Non medical and indirect costs account for as much as 44.97% of the total cost prior to treatment and to 6.59% after treatment, with an overall 71.38% decrease. Adopting a societal perspective in the actual clinical practice of the Italian participating centres, the ICER of biologic therapies for treating plaque psoriasis amounted to ?18634.40 per QALY gained--a value far from the ?28656.30 obtained by adopting a third-party payer perspective. CONCLUSION: Our study confirms that chronic psoriasis subjects patients to a considerable burden, together with their families and caregivers, stressing how important it is to take the societal perspective into consideration during the appraisal process. Besides, using data derived from Italian actual practice, treatment with biologics shows a noteworthy benefit in social terms. PMID- 26370323 TI - U-shaped relationship between uric acid and residual renal function decline in continuous ambulatory peritoneal dialysis patients. AB - AIM: There is little information on the relationship between uric acid (UA) and residual renal function (RRF) in continuous ambulatory peritoneal dialysis (CAPD). The aim of this research is to study the influence of UA on RRF decline in CAPD patients. METHODS: A retrospective observational cohort study of 304 patients who started CAPD without anuria between 2001 and 2010 was conducted at a single medical center. The outcomes measured in the study included the rate of RRF decline and anuria. A multiple ordinal logistic regression model with backward elimination was conducted to determine the independent factors of the slope of RRF decline. A Cox proportional hazard model was conducted to determine the independent variables of time to anuria. RESULTS: The average rate of RRF decline was -0.12 +/- 0.22 mL/min per month. Multivariate analysis showed that lower UA group (<0.372 mmol/L), higher UA group (?0.421 mmol/L), male gender, diabetes mellitus (DM), the use of calcium channel blocker (CCB), and RRF at baseline were linked positively with the rate of RRF decline; on the other hand, independence in dialysate exchanges and BUN were negatively associated with the risk of RRF decline. In addition, male gender, DM, diuretics, and CCB were associated with a higher risk of progression to anuria, whereas 24-h urine amount at baseline conferred a protective role in the development of anuria. CONCLUSIONS: A U-shaped relationship was found between UA levels and the rate of RRF decline in patients on CAPD, with a faster decline rate in those of higher and lower UA groups. PMID- 26370324 TI - Introducing PRISMA as a requirement. PMID- 26370322 TI - The beta-cell GHSR and downstream cAMP/TRPM2 signaling account for insulinostatic and glycemic effects of ghrelin. AB - Gastric hormone ghrelin regulates insulin secretion, as well as growth hormone release, feeding behavior and adiposity. Ghrelin is known to exert its biological actions by interacting with the growth hormone secretagogue-receptor (GHSR) coupled to G(q/11)-protein signaling. By contrast, ghrelin acts on pancreatic islet beta-cells via Gi-protein-mediated signaling. These observations raise a question whether the ghrelin action on islet beta-cells involves atypical GHSR and/or distinct signal transduction. Furthermore, the role of the beta-cell GHSR in the systemic glycemic effect of ghrelin still remains to be defined. To address these issues, the present study employed the global GHSR-null mice and those re-expressing GHSR selectively in beta-cells. We here report that ghrelin attenuates glucose-induced insulin release via direct interaction with ordinary GHSR that is uniquely coupled to novel cAMP/TRPM2 signaling in beta-cells, and that this beta-cell GHSR with unique insulinostatic signaling largely accounts for the systemic effects of ghrelin on circulating glucose and insulin levels. The novel beta-cell specific GHSR-cAMP/TRPM2 signaling provides a potential therapeutic target for the treatment of type 2 diabetes. PMID- 26370325 TI - Astragulus polysaccharide-loaded fibrous mats promote the restoration of microcirculation in/around skin wounds to accelerate wound healing in a diabetic rat model. AB - Tissue engineering scaffolds (TES) can carry numerous biomacromolecules and cells, and they have been widely used in diabetic skin wound healing with positive effects. However, the bioactive retention of biomacromolecules and cells during fabrication and storage is still a factor restricting their use. Moreover, impaired blood supply in/around poorly healing diabetic skin wounds has not been considered. In the present study, a bioactive natural substance of Astragalus polysaccharide (APS), which has stable and confirmed effects on endothelial protection, was embedded into fibrous TES by electrospinning. The administration of APS-loaded TES on the skin wound in a diabetic rat model led to a dose dependent promotion in skin blood flow around wounds and an increase in endoglin expression and microvessel density in regenerated skin tissues. Furthermore, the higher loading of APS in TES led to faster collagen synthesis, appendage and epidermal differentiation, and wound closure. In summary, the combination of APS with TES is a potentially novel therapeutic strategy for diabetic skin wound healing, as it not only mimics the ultrastructure of extracellular matrixes but also restores skin microcirculation. PMID- 26370326 TI - Upregulation of GSK3beta Contributes to Brain Disorders in Elderly REGgamma knockout Mice. AB - GSK3beta regulates some functions of the brain, but the mechanisms involved in the maintenance of GSK3beta protein stability remain ambiguous. REGgamma, an important proteasome activator for ubiquitin-independent protein degradation, has been shown to degrade certain intact proteins and is involved in the regulation of important biological processes. Here we demonstrate that REGgamma promotes the degradation of GSK3beta protein in vitro and in vivo. With increased GSK3beta activity, REGgamma knockout (REGgamma-/-) mice exhibit late-onset sensorimotor gating and cognitive deficiencies including decreased working memory, hyperlocomotion, increased stereotype, defective prepulse inhibition (PPI), and disability in nest building, at the age of 8 months or older. Inhibition of GSK3beta rescued the compromised PPI phenotypes and working memory deficiency in the knockout mice. Also, we found an age-dependent decrease in the trypsin-like proteasomal activity in REGgamma-/- mice brains, which may be reflective of a lack of degradation of GSK3beta. Collectively, our findings reveal a novel regulatory pathway in which the REGgamma-proteasome controls the steady-state level of GSK3beta protein. Dysfunction in this non-canonical proteasome degradation pathway may contribute to the sensorimotor gating deficiency and cognitive disorders in aging mice. PMID- 26370327 TI - Consequences of Adolescent Ethanol Consumption on Risk Preference and Orbitofrontal Cortex Encoding of Reward. AB - Critical development of the prefrontal cortex occurs during adolescence, a period of increased independence marked by decision making that often includes engagement in risky behaviors, such as substance use. Consumption of alcohol during adolescence has been associated with increased impulsivity that persists across the lifespan, an effect which may be caused by long-term disruptions in cortical processing of rewards. To determine if alcohol consumption alters cortical encoding of rewards of different sizes and probabilities, we gave rats limited access to alcohol in gelatin during adolescence only. In adulthood, we recorded the electrophysiological activity of individual neurons of the orbitofrontal cortex while rats performed a risk task that varied the level of risk from day-to-day. Rats that had consumed higher levels of alcohol showed increased risk preference in the task compared with control and low alcohol consuming rats. Patterns of neuronal responses were identified using principal component analysis. Of the multiple patterns observed, only one was modulated by adolescent alcohol consumption and showed strongest modulation after reward receipt. This subpopulation of neurons showed blunted firing rates following rewards in alcohol-consuming rats, suggesting a mechanism through which adolescent alcohol exposure may have lasting effects on reward processing in the context of decision making. The differences in OFC responses between high alcohol consumers and control animals not given access to alcohol support the idea that, regardless of potential variability in innate alcohol preferences, voluntary consumption of alcohol during adolescence biases choice patterns longitudinally through alterations in cortical function. PMID- 26370328 TI - Novel, human cell line-derived recombinant factor VIII (Human-cl rhFVIII, Nuwiq(r) ) in children with severe haemophilia A: efficacy, safety and pharmacokinetics. AB - INTRODUCTION: Nuwiq(r) (Human-cl rhFVIII) is a new-generation recombinant factor VIII (rFVIII) protein, without chemical modification or fusion to any other protein, produced in a human cell line. AIM/METHODS: This prospective, open label, multinational phase III study assessed the efficacy and safety of Human-cl rhFVIII in 59 previously treated patients (PTPs) with severe haemophilia A aged 2 12 years (2-5 [N = 29]; 6-12 [N = 30]) during standard prophylaxis (>=50 exposure days and >=6 months). Efficacy in treating breakthrough bleeds and during surgical prophylaxis was also assessed. RESULTS: An initial pharmacokinetic assessment (N = 13 per age subgroup) demonstrated comparable results with the one stage and chromogenic assays. Mean (SD) half-life was 11.9 (5.4) and 13.1 (2.6) hours in children aged 2-5 years and 6-12 years respectively (one-stage assay). Prophylactic efficacy, based on mean monthly bleeding rate, was 'excellent' or 'good' in 91.5% of children for all bleeds and in 96.6% of children for spontaneous bleeds. Mean (SD) annualized bleeding rate was 4.12 (5.22) [median 1.9] for all bleeds, 1.50 (3.32) [median 0] for spontaneous bleeds and 2.34 (3.54) [median 1.57] for traumatic bleeds. There were no major, life-threatening bleeds. Efficacy was 'excellent' or 'good' in the treatment of 82.4% of breakthrough bleeds. Overall efficacy during five major surgeries was rated as 'excellent'. There were no FVIII inhibitors or treatment-related serious adverse events. CONCLUSION: These results in paediatric PTPs indicate that Human-cl rhFVIII is effective for the prevention and treatment of bleeds. PMID- 26370329 TI - Hydration status influences seed fire tolerance in temperate European herbaceous species. AB - Prescribed burning is an important management tool in many parts of the world. While natural fires generally occur during the driest and warmest period of the year, prescribed burning is often timed out-of-season, when there is higher soil moisture and lower biomass combustibility. However, fire season may influence seedling recruitment after fire, e.g. through the effect of seed hydration status on fire tolerance. In non-fire-prone temperate regions, anthropogenic fire may occur exclusively in periods outside the growing season with higher soil moisture, which may have negative consequences on seedling recruitment. Fire tolerance of moist and dry seeds of 16 temperate European herbaceous species belonging to four families was assessed using heat treatment of 100 degrees C for 5 min and subsequent germination trials. Moist seeds of Asteraceae, Poaceae and Brassicaceae had a predominantly negative reaction to the heat treatment, while those of Fabaceae tolerated it or germination was even enhanced. The reaction of dry seeds was completely different, with positive responses in three species of the Fabaceae and fire tolerance in species of other families. Our results point out that hydration status may significantly influence the post-fire germination of seeds. Dry seeds were found to tolerate high heat, while moist seeds were harmed in more than half of the species. This implies that if prescribed burning is applied in temperate grasslands of Europe, it should be timed to dry periods of the dormant season in order to protect seeds from negative effects of fire. PMID- 26370330 TI - Diagnosis of cerebrospinal fluid rhinorrhea: an evidence-based review with recommendations. AB - BACKGROUND: Diagnostic strategies employed for cases of cerebrospinal fluid (CSF) rhinorrhea vary widely due to limited evidence-based guidance. METHODS: A systematic review of the literature was performed using PubMed, EMBASE, and Cochrane databases from January 1990 through September 2014, to examine 9 diagnostic and localization modalities for CSF rhinorrhea. Benefit-harm assessments, value judgments and recommendations were made based on the available evidence. Study exclusion criteria were language other than English, pre-1990 studies, case reports, and nonrhinologic leak. All authors agreed on recommendations through an iterative process. RESULTS: We reviewed 68 studies examining 9 practices pertinent to the diagnosis of CSF rhinorrhea, with a highest aggregate grade of evidence of C. The literature does not support the use of the ring sign, glucose testing, radionuclide cisternography (RNC), or computed tomography cisternography (CTC) for identification of CSF leak. Beta-2 transferrin is the most reliable confirmatory test for CSF leak. High-resolution CT (HRCT) is then recommended as the first-line study for localization. Magnetic resonance cisternography (MRC) should be used for CSF leak identification as a second line for each of these if beta-2 transferrin is not available or if HRCT is ambiguous. Intrathecal fluorescein (IF) may also be of benefit in certain clinical scenarios. CONCLUSION: Despite relatively low levels of evidence, recommendations for the diagnosis and management of CSF rhinorrhea can be made based on the current literature. Higher-level studies are needed to better determine optimal diagnostic and clinical management approaches. PMID- 26370331 TI - Two cases of uterine malignant lymphoma diagnosed by needle biopsy. AB - The incidence of primary malignant lymphoma arising in the female genital tract is extremely rare and constitutes approximately 0.05% of malignant tumors. Uterine malignant lymphoma develops in the endometrial stroma, causing minimal necrosis. It is therefore difficult to diagnose malignant lymphoma, as it does not involve genital bleeding or epithelial defects. We have performed transcervical needle biopsies from deep in the myometrium, with the purpose of diagnosing uterine muscle layer lesions, such as leiomyosarcoma, but this is an unusual method. In this report, we suggest that transcervical needle biopsy is useful in the diagnosis of uterine malignant lymphoma. PMID- 26370332 TI - Dietary protein ingested before and during short photoperiods makes an impact on affect-related behaviours and plasma composition of amino acids in mice. AB - In mammals, short photoperiod is associated with high depression- and anxiety like behaviours with low levels of the brain serotonin and its precursor tryptophan (Trp). Because the brain Trp levels are regulated by its ratio to large neutral amino acids (Trp:LNAA) in circulation, this study elucidated whether diets of various protein sources that contain different Trp:LNAA affect depression- and anxiety-like behaviours in C57BL/6J mice under short-day conditions (SD). In the control mice on a casein diet, time spent in the central area in the open field test (OFT) was lower in the mice under SD than in those under long-day conditions (LD), indicating that SD exposure induces anxiety-like behaviour. The SD-induced anxiety-like behaviour was countered by an alpha lactalbumin diet given under SD. In the mice that were on a gluten diet before transition to SD, the time spent in the central area in the OFT under SD was higher than that in the SD control mice. Alternatively, mice that ingested soya protein before the transition to SD had lower immobility in the forced swim test, a depression-like behaviour, compared with the SD control. Analysis of Trp:LNAA revealed lower Trp:LNAA in the SD control compared with the LD control, which was counteracted by an alpha-lactalbumin diet under SD. Furthermore, mice on gluten or soya protein diets before transition to SD exhibited high Trp:LNAA levels in plasma under SD. In conclusion, ingestion of specific proteins at different times relative to photoperiodic transition may modulate anxiety- and/or depression-like behaviours, partially through changes in plasma Trp:LNAA. PMID- 26370333 TI - Endoplasmic reticulum stress is involved in apoptosis of detrusor muscle in streptozocin-induced diabetic rats. AB - AIMS: Endoplasmic reticulum stress (ERS) has been proven to be associated with apoptosis and plays a critical role in the development of many diabetic complications. In the pathogenesis of diabetic cystopathy (DCP), the role of ERS is still unclear. Our study is aimed at the investigation of the involvement of ERS-associated detrusor muscle apoptosis in streptozocin (STZ)-induced diabetic rats. METHODS: At different timepoints (4, 8, 12, and 16 weeks after induction of type 1 diabetic rat models), hematoxylin & eosin (H&E) staining was performed to assess the histological changes of the diabetic detrusor; the sub-cellular ultrastructure, especially the zone of endoplasmic reticulum (ER), was observed by transmission electron microscopy (TEM), and the terminal deoxynucleotidyl transferase-mediated DNA nick-end labeling (TUNEL) staining was used to identify the enhanced apoptosis. Moreover, the expression of three hallmarks of ERS associated apoptosis, including glucose-regulated protein 78 (GRP78), CCAAT/enhancer-binding protein homologous protein (CHOP), and caspase12, was detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. RESULTS: Light microscopic impairments of histology, including progressive loosely packed muscle bundles and increased fibrous tissue, can be seen; the ultrastructural changes featuring the swollen and fused cisternaes in ER zone and deformed nucleus were also observed in the detrusor smooth muscle (DSM). Increased apoptosis and elevated expression of GRP78, CHOP, and caspase12 at both protein and mRNA levels in a time-dependent fashion were detected. CONCLUSIONS: The occurrence of ERS-associated apoptosis may be involved in the development of DCP and may contribute to the diabetic detrusor impairment. Neurourol. Urodynam. 36:65-72, 2017. (c) 2015 Wiley Periodicals, Inc. PMID- 26370335 TI - Diagnostic approach in lymphoplasmacytic plaque. AB - BACKGROUND: Lymphoplasmacytic plaque (LPP) is a recently described rare skin disease characterized by a dense dermal lymphohistiocytic infiltrate with polyclonal plasma cells. The clinical picture is distinct with reddish to brownish plaque with a predilection for the lower leg. LPP typically affects children. OBJECTIVE: To define clinical and histologic criteria of LPP and to develop a diagnostic flow chart. METHODS: We investigated six of our own LPP cases. Immunoglobulin light chains, IgG, IgG4, CD31, CD163 as a histiocytic marker were examined by immunohistochemistry. PCR-based molecular studies were conducted for borrelia sp., mycobacterial and leishmania sp. Moreover, 10 cases, which have been reported in the literature, were checked for the same features. RESULTS: We could differentiate three main histological patterns (superficial band-like only, [deep] dermal only and mixed). Acanthosis and interface dermatitis are key features in cases with a superficial band-like or mixed infiltrate. Granulomas and giant cells could be only found in about 30% of the cases. The number of plasma cells was variable accounting for 5-40% of the infiltrate. The number of blood vessels was increased in the majority of the cases. 'Free-floating' collagen bundles surrounded by histiocytes (pseudorosettes) were identified as a new histological feature. An infectious agent could be excluded in all cases. CONCLUSIONS: LPP is a long-standing skin disease, which may also occur in adults and in other body regions than the lower leg. Reproducible clinical and histological criteria allow delineating a diagnostic work-up for LPP. PMID- 26370334 TI - An amino acid code for irregular and mixed protein packing. AB - To advance our understanding of protein tertiary structure, the development of the knob-socket model is completed in an analysis of the packing in irregular coil and turn secondary structure packing as well as between mixed secondary structure. The knob-socket model simplifies packing based on repeated patterns of two motifs: a three-residue socket for packing within secondary (2 degrees ) structure and a four-residue knob-socket for tertiary (3 degrees ) packing. For coil and turn secondary structure, knob-sockets allow identification of a correlation between amino acid composition and tertiary arrangements in space. Coil contributes almost as much as alpha-helices to tertiary packing. In irregular sockets, Gly, Pro, Asp, and Ser are favored, while in irregular knobs, the preference order is Arg, Asp, Pro, Asn, Thr, Leu, and Gly. Cys, His,Met, and Trp are not favored in either. In mixed packing, the knob amino acid preferences are a function of the socket that they are packing into, whereas the amino acid composition of the sockets does not depend on the secondary structure of the knob. A unique motif of a coil knob with an XYZ beta-sheet socket may potentially function to inhibit beta-sheet extension. In addition, analysis of the preferred crossing angles for strands within a beta-sheet and mixed alpha-helice/beta-sheet identifies canonical packing patterns useful in protein design. Lastly, the knob socket model abstracts the complexity of protein tertiary structure into an intuitive packing surface topology map. PMID- 26370336 TI - DNA-protection and antioxidant properties of fermentates from Bacillus amyloliquefaciens B-1895 and Bacillus subtilis KATMIRA1933. AB - DNA protective and antioxidant activity of Bacillus amyloliquefaciens B-1895 and Bacillus subtilis KATMIRA1933 were evaluated by Escherichia coli-based Lux biosensors. Two biosensor strains of E. coli, MG1655 (pColD-lux) and MG1655 (pSoxS-lux), which react on DNA damage and superoxide-anion radical activity, were used. SOS-response and Sox-response were stimulated by addition of dioxidine (2,3-Quinoxalinedimethanol,1,4-dioxide) and paraquat (N,N'-dimethyl-4,4' bipyridinium dichloride) respectively. Preparations of both Bacillus fermentates demonstrated DNA protective and antioxidant (superoxide scavenging) activity (up to 60.19%). The strain K1933 is, in general, characterized by higher DNA protective activity (28.85%), with parameters of antioxidant activity of both bacilli strains being statistically not significantly different. Sporogenous potential probiotic micro-organisms with antioxidant and DNA protective activities can become an effective tool for compensation of various negative oxidative stress processes in humans. SIGNIFICANCE AND IMPACT OF THE STUDY: In humans, oxidative stress is a cause or an important component of many serious diseases, as well as being one of the age influencing factors. Environmental stresses lead to the increase in levels of reactive oxygen species (ROS). Oxidative DNA damage is a side effect of nonspecific inflammation. These human health challenging factors trigger the search for health-promoting bacteria capable of production of antioxidants and DNA-protectors. In this study, two Bacillus strains of interest were shown to produce noticeable DNA protective and antioxidant activities. PMID- 26370338 TI - Cancer risk in the transgender community. PMID- 26370337 TI - Manifestation of a Second Dirac Surface State and Bulk Bands in THz Radiation from Topological Insulators. AB - Topological insulators (TIs) are interesting quantum matters that have a narrow bandgap for bulk and a Dirac-cone-like conducting surface state (SS). The recent discovered second Dirac surface state (SS) and bulk bands (BBs) located ~1.5 eV above the first SS are important for optical coupling in TIs. Here, we report on the time-domain measurements of THz radiation generated from TIs n-type Cu(0.02)Bi2Se3 and p-type Bi2Te3 single crystals by ultrafast optical pulse excitation. The observed polarity-reversal of the THz pulse originated from transient current is unusual, and cannot be reconciled with the photo-Dember effect. The second SS and BBs are found to be indispensable for the explanation of the unusual phenomenon. Thanks to the existence of the second SS and BBs, TIs manifest an effective wide band gap in THz generation. The present study demonstrates that time-domain THz spectroscopy provide rich information of the optical coupling and the electronic structure of TIs. PMID- 26370339 TI - Adjuvant radiation for patients with melanoma. PMID- 26370340 TI - Clinical cancer genomic analysis: data engineering required. PMID- 26370341 TI - Edinburgh Festival Fringe Round Up. PMID- 26370342 TI - Faces of breast cancer: a personal approach. PMID- 26370343 TI - SABR vs surgery for NSCLC in the media. PMID- 26370344 TI - Fewer than three doses of HPV vaccine. PMID- 26370345 TI - Fewer than three doses of HPV vaccine. PMID- 26370346 TI - Fewer than three doses of HPV vaccine - Authors' reply. PMID- 26370347 TI - Will the revised class waiver list make it? PMID- 26370348 TI - Correction to Lancet Oncol 2015; 16: 1127. PMID- 26370349 TI - Correction to Lancet Oncol 2015; 16: 388. PMID- 26370350 TI - Correction to Lancet Oncol 2011; 12: 1051. PMID- 26370351 TI - Correction to Lancet Oncol 2015; 16: 634, 637. PMID- 26370352 TI - Correction to Lancet Oncol 2015; 16: 967-78. PMID- 26370353 TI - Consensus on biomarkers for neuroendocrine tumour disease. AB - Management of neuroendocrine neoplasia represents a clinical challenge because of its late presentation, lack of treatment options, and limitations in present imaging modalities and biomarkers to guide management. Monoanalyte biomarkers have poor sensitivity, specificity, and predictive ability. A National Cancer Institute summit, held in 2007, on neuroendocrine tumours noted biomarker limitations to be a crucial unmet need in the management of neuroendocrine tumours. A multinational consensus meeting of multidisciplinary experts in neuroendocrine tumours assessed the use of current biomarkers and defined the perquisites for novel biomarkers via the Delphi method. Consensus (at >75%) was achieved for 88 (82%) of 107 assessment questions. The panel concluded that circulating multianalyte biomarkers provide the highest sensitivity and specificity necessary for minimum disease detection and that this type of biomarker had sufficient information to predict treatment effectiveness and prognosis. The panel also concluded that no monoanalyte biomarker of neuroendocrine tumours has yet fulfilled these criteria and there is insufficient information to support the clinical use of miRNA or circulating tumour cells as useful prognostic markers for this disease. The panel considered that trials measuring multianalytes (eg, neuroendocrine gene transcripts) should also identify how such information can optimise the management of patients with neuroendocrine tumours. PMID- 26370354 TI - Treatment approaches for EGFR-inhibitor-resistant patients with non-small-cell lung cancer. AB - Discovery of activating mutations in EGFR and their use as predictive biomarkers to tailor patient therapy with EGFR tyrosine kinase inhibitors (TKIs) has revolutionised treatment of patients with advanced EGFR-mutant non-small-cell lung cancer (NSCLC). At present, first-line treatment with EGFR TKIs (gefitinib, erlotinib, and afatinib) has been approved for patients harbouring exon 19 deletions or exon 21 (Leu858Arg) substitution EGFR mutations. These agents improve response rates, time to progression, and overall survival. Unfortunately, patients develop resistance, limiting patient benefit and posing a challenge to oncologists. Optimum treatment after progression is not clearly defined. A more detailed understanding of the biology of EGFR-mutant NSCLC and the mechanisms of resistance to targeted therapy mean that an era of treatment approaches based on rationally developed drugs or therapeutic strategies has begun. Combination approaches-eg, dual EGFR blockade-to overcome resistance have been trialled and seem to be promising but are potentially limited by toxicity. Third-generation EGFR-mutant-selective TKIs, such as AZD9291 or rociletininb, which target Thr790Met-mutant tumours, the most common mechanism of EGFR TKI resistance, have entered clinical trials, and exciting, albeit preliminary, efficacy data have been reported. In this Review, we summarise the scientific literature and evidence on therapy options after EGFR TKI treatment for patients with NSCLC, aiming to provide a guide to oncologists, and consider how to maximise therapeutic advances in outcomes in this rapidly advancing area. PMID- 26370355 TI - Inherited cylindromas: lessons from a rare tumour. AB - Cylindroma is a rare skin tumour that is inherited in several skin-tumour syndromes caused by germline mutations in the tumour suppressor gene, CYLD. In this Review, we provide insight into the clinical features of patients who develop multiple cylindromas and other related tumours. The CYLD protein is also dysfunctional in various sporadic cancers and we discuss how such dysfunction relates to the role of CYLD in regulating key cellular pathways. Clinical management of patients with germline CYLD mutations is challenging and we discuss genetic counselling and surgical interventions. Finally, we discuss how the study of these rare syndromes might provide insights into understanding more common diseases. PMID- 26370356 TI - Consensus on the management of intracranial germ-cell tumours. AB - The management of intracranial germ-cell tumours is complex because of varied clinical presentations, tumour sites, treatments and outcomes, and the need for multidisciplinary input. Participants of the 2013 Third International CNS Germ Cell Tumour Symposium (Cambridge, UK) agreed to undertake a multidisciplinary Delphi process to identify consensus in the clinical management of intracranial germ-cell tumours. 77 delegates from the symposium were selected as suitable experts in the field and were invited to participate in the Delphi survey, of which 64 (83%) responded to the invitation. Invited participants represented multiple disciplines from Asia, Australasia, Europe, and the Americas. 38 consensus statements encompassing aspects of intracranial germ-cell tumour work up, staging, treatment, and follow-up were prepared. To achieve consensus, statements required at least 70% agreement from at least 60% of respondents. Overall, 34 (89%) of 38 statements met consensus criteria. This international Delphi approach has defined key areas of consensus that will help guide and streamline clinical management of patients with intracranial germ-cell tumours. Additionally, the Delphi approach identified areas of different understanding and clinical practice internationally in the management of these tumours, areas which should be the focus of future collaborative studies. Such efforts should translate into improved patient outcomes. PMID- 26370357 TI - Is high pressure postdilation safe in bioresorbable vascular scaffolds? Optical coherence tomography observations after noncompliant balloons inflated at more than 24 atmospheres. AB - OBJECTIVES: Optical coherence tomography (OCT) was used to investigate integrity and expansion of bioresorbable drug-eluting scaffolds (BVS) after high-pressure postdilation (HPPD). BACKGROUND: Because of concerns about the risk of BVS damage, postdilation was not recommended and applied in the existing randomized studies and most registries. Recent real world data suggest incomplete BVS expansion cause higher rates of thrombosis. In vivo confirmation of the safety of high pressure postdilation is of paramount importance. METHODS: Data from final OCT examination of consecutive implanted BVS, postdilated with noncompliant (NC) balloons at pressure >=24 atm were analyzed. The following stent performance indices were assessed with OCT: mean and minimal lumen and scaffold area, residual area stenosis (RAS), incomplete strut apposition (ISA), tissue prolapse, eccentricity index (EI), symmetry index (SI), strut fractures, and edge dissections. RESULT: Twenty-two BVS postdilated at high pressure were analyzed. The average maximal postdilation balloon inflation (maxPD) was 28 +/- 3 atm. High pressure OPN NC Balloon (SIS Medical AG, Winterthur Switzerland) was used in 41% of postdilations with a maximal PD of 30 +/- 4.7 atm. Final mean and minimal lumen area were 6.8 +/- 1.4 and 5.5 +/- 1.4 mm(2) , respectively. OCT showed low percentage of RAS (16 +/- 9.6%), and low percentage of ISA (1.8 +/- 2.4%). Mean EI was 0.86 +/- 0.02 and SI 0.35 +/- 0.14. OCT analysis showed one edge dissection and no scaffold fractures. CONCLUSIONS: BVS deployment optimization using HPPD does not cause BVS disruption and is associated with a good BVS expansion, low rate of strut malapposition and edge dissections. PMID- 26370358 TI - Concealed pregnancy: a concept analysis. AB - AIM/DESIGN: A concept analysis of concealed pregnancy was undertaken using Walker and Avant's framework to examine the attributes, characteristics and uses of the concept in maternity care. BACKGROUND: Understanding the concept of concealed pregnancy is critical as failing to do so adds the risk of maternal and neonatal morbidity and mortality. Reviewing the literature and selected empirical referents indicated that concealed pregnancy has been predominantly viewed through a biomedical lens. Confusion exists around the definitions of denied and concealed pregnancy. DATA SOURCES: A systematic search of five bibliographic databases using keywords from the years 1960-2014. METHODS: Walker and Avant's framework was used to guide the concept analysis. A thematic analysis of reviewed papers identified the main characteristics of concealed pregnancy. RESULTS: Concealed pregnancy was conceptualized as a process and the critical attributes are secrecy, hiding, daytime story, staying away and avoidance. This process involves avoidance and if this includes failing to access healthcare can lead to catastrophic outcomes such as maternal and neonatal death. Antecedents, attributes and consequences of concealed pregnancy are also identified. CONCLUSIONS: Understanding the concept of concealed pregnancy and its antecedents, attributes and consequences may assist in risk identification of women who conceal a pregnancy. This concept analysis has identified a need for further exploration of the coping styles and psychosocial processes involved in women concealing and revealing a pregnancy. PMID- 26370360 TI - Sum uncertainty relations for arbitrary N incompatible observables. AB - We formulate uncertainty relations for arbitrary N observables. Two uncertainty inequalities are presented in terms of the sum of variances and standard deviations, respectively. The lower bounds of the corresponding sum uncertainty relations are explicitly derived. These bounds are shown to be tighter than the ones such as derived from the uncertainty inequality for two observables [Phys. Rev. Lett. 113, 260401 (2014)]. Detailed examples are presented to compare among our results with some existing ones. PMID- 26370359 TI - Saccadic modulation of stimulus processing in primary visual cortex. AB - Saccadic eye movements play a central role in primate vision. Yet, relatively little is known about their effects on the neural processing of visual inputs. Here we examine this question in primary visual cortex (V1) using receptive-field based models, combined with an experimental design that leaves the retinal stimulus unaffected by saccades. This approach allows us to analyse V1 stimulus processing during saccades with unprecedented detail, revealing robust perisaccadic modulation. In particular, saccades produce biphasic firing rate changes that are composed of divisive gain suppression followed by an additive rate increase. Microsaccades produce similar, though smaller, modulations. We furthermore demonstrate that this modulation is likely inherited from the LGN, and is driven largely by extra-retinal signals. These results establish a foundation for integrating saccades into existing models of visual cortical stimulus processing, and highlight the importance of studying visual neuron function in the context of eye movements. PMID- 26370362 TI - Child oral health from the professional perspective - a global ICF-CY survey. AB - BACKGROUND: The International Classification of Functioning, Disability and Health Children and Youth version (ICF-CY) (WHO) may serve as a tool for the application of holistic models of oral health. AIM: The ICF-CY Global Oral Health Survey explored international professional opinion regarding factors relating to child oral health, including social environment, functioning, activity, and participation. METHODS: Networking resulted in 514 professionals from 81 countries registering for a two-round Delphi survey online. Participants were pooled into 18 groups according to six WHO world regions and three professional groups. In a randomized stratification process, eight from each pool (n = 144) completed the survey. The first round consisted of eight open-ended questions. Open-expression replies were analysed for meaningful concepts and linked using established rules to the ICF-CY. In the second round, items were rated for their relevance to oral health (86% response rate). RESULTS: A total of 86 ICF-CY items and 31 other factors were considered relevant to child oral health and function by at least 80% of professionals. CONCLUSIONS: The ICF-CY can describe the holistic experience of oral health in children from the professional perspective. The data from this study will contribute to the development of an ICF-CY Core Set in Oral Health. PMID- 26370361 TI - Rise of multiple insecticide resistance in Anopheles funestus in Malawi: a major concern for malaria vector control. AB - BACKGROUND: Deciphering the dynamics and evolution of insecticide resistance in malaria vectors is crucial for successful vector control. This study reports an increase of resistance intensity and a rise of multiple insecticide resistance in Anopheles funestus in Malawi leading to reduced bed net efficacy. METHODS: Anopheles funestus group mosquitoes were collected in southern Malawi and the species composition, Plasmodium infection rate, susceptibility to insecticides and molecular bases of the resistance were analysed. RESULTS: Mosquito collection revealed a predominance of An. funestus group mosquitoes with a high hybrid rate (12.2 %) suggesting extensive species hybridization. An. funestus sensu stricto was the main Plasmodium vector (4.8 % infection). Consistently high levels of resistance to pyrethroid and carbamate insecticides were recorded and had increased between 2009 and 2014. Furthermore, the 2014 collection exhibited multiple insecticide resistance, notably to DDT, contrary to 2009. Increased pyrethroid resistance correlates with reduced efficacy of bed nets (<5 % mortality by Olyset((r)) net), which can compromise control efforts. This change in resistance dynamics is mirrored by prevalent resistance mechanisms, firstly with increased over-expression of key pyrethroid resistance genes (CYP6Pa/b and CYP6M7) in 2014 and secondly, detection of the A296S-RDL dieldrin resistance mutation for the first time. However, the L119F-GSTe2 and kdr mutations were absent. CONCLUSIONS: Such increased resistance levels and rise of multiple resistance highlight the need to rapidly implement resistance management strategies to preserve the effectiveness of existing insecticide-based control interventions. PMID- 26370363 TI - Successful Treatment of Intractable Fluid Retention Using Tolvaptan After Treatment for Postoperative Mediastinitis in a Patient With a Left Ventricular Assist Device. AB - The use of implantable continuous-flow left ventricular assist devices (LVADs) as a bridge to transplant is effective for patients with congestive heart failure (HF). However, some patients develop congestive symptoms due to right-sided HF even with LVAD support. Tolvaptan, a vasopressin type 2 receptor antagonist, corrects both congestion and hyponatremia in patients with advanced HF. We report herein a case involving a patient who underwent LVAD implantation and developed hyponatremia and congestive symptoms after negative-pressure wound therapy and omental transposition for postoperative mediastinitis. Hemodynamic evaluation performed after negative-pressure wound therapy revealed elevation of both right arterial pressure and pulmonary capillary wedge pressure, and suggested biventricular dysfunction despite LVAD support. Symptoms improved after starting administration of tolvaptan. Tolvaptan may be useful for correcting hyponatremia and volume overload in patients under LVAD support. PMID- 26370364 TI - Optimal Graft Size of Modified Blalock-Taussig Shunt for Biventricular Circulation in Neonates and Small Infants. AB - The modified Blalock-Taussig shunt (mBTS) is one of the most important palliative procedures in congenital heart surgery. However, in neonates and small infants, operative mortality and morbidity due to excessive pulmonary blood flow or shunt failure remains high. In this study, a small shunt graft (3.0-mm diameter) was estimated to determine the optimal shunt graft size of BTS as an initial palliation for ultimate biventricular circulation. Eighteen patients weighing an average 3.5 kg who underwent mBTS from July 2004 to January 2013 at our institute were reviewed. We divided the study cohort into two groups: group S (n = 10) included patients with 3.0-mm diameter shunt grafts, and group L (n = 8) included patients with 3.5-mm diameter shunt grafts. There were no hospital deaths or shunt occlusion in either group. One group L patient (12.5%) had cardiogenic shock due to excessive pulmonary blood flow. There were no differences in postoperative arterial oxygen saturation (SaO2) between the groups. There were no differences in body weight at intracardiac repair (ICR) between the groups. During the interstage to ICR, body weight gain was significantly greater in group S than in group L (P = 0.008). The small shunt graft (3.0-mm diameter) in BTS was safe, provided adequate pulmonary blood flow, and led to significant weight gain between mBTS and ICR for ultimate biventricular circulation in neonates and small infants with low body weight. PMID- 26370365 TI - Impact of Catheter Sheath Insertion into the Radial Artery on Vascular Endothelial Function Assessed by Reactive Hyperemia Peripheral Arterial Tonometry. AB - The transradial approach has been used for coronary procedures, but this procedure carries a risk of injury to the endothelium of the radial artery. In this study, the vascular dysfunction caused by transradial catheterization was examined using reactive hyperemia peripheral arterial tonometry (RH-PAT), a recently developed technique for assessing endothelial function in digits, and the differences in injuries were compared according to the size of sheath.Forty three patients undergoing transradial catheterization with 6-Fr sheaths (n = 17) or 4-Fr/5-Fr (non-6-Fr; n = 26) sheaths underwent RH-PAT using an Endo-PAT2000 before, the day after, and 6 months after catheterization. RH-PAT was assessed in the arm of sheath placement and in the other arm as a control.RH-PAT values decreased from 2.42 +/- 0.67 before catheterization to 2.08 +/- 0.41 the day after catheterization in the 6-Fr group (P = 0.031); this was more evident in patients with a longer procedure time (> 91 minutes). In contrast, the change in the non-6-Fr group was not significant. RH-PAT of the non-catheterized arm was unchanged in both groups. At 6 months after catheterization, RH-PAT values in the 6-Fr group had not completely returned to baseline.In conclusion, the insertion of a 6-Fr catheter sheath into the radial artery, especially with a longer procedure time, impaired vascular endothelial function assessed by RH-PAT the day after the procedure and was sustained for 6 months. Thus, the use of smaller size sheaths (< 6-Fr) with a shorter procedure should be considered when performing transradial catheterization. PMID- 26370366 TI - Effective Management of Atrioventricular Interval for Paroxysmal Atrial Fibrillation That Developed After DDDR Pacemaker Implantation in a Sick Sinus Syndrome Patient. AB - A 68-year-old man with sick sinus syndrome (SSS) was referred to our department for pacemaker implantation. After implantation of a pacemaker with rate responsive dual chamber (DDDR) mode and minimized ventricular pacing (MVP) functions, paroxysmal atrial fibrillation (PAF) repeatedly developed. Pacemaker memory showed that the intrinsic atrioventricular (AV) (atrial pacing-ventricular sensing [Ap-Vs]) interval was paradoxically prolonged during rate-responsive atrial single-chamber (AAIR) mode rapid pacing because of MVP. Accordingly, to eliminate the paradoxical prolongation of the AV interval during rapid atrial pacing, we changed MVP to medium AV hysteresis and conducted DDDR mode pacing with rate-dependent AV delay. PAF then sharply decreased without antiarrhythmic drugs. PMID- 26370367 TI - Letter by Cacko, et al Regarding Article, "Improvement of Cardiac Function by Increasing Stimulus Strength During Left Ventricular Pacing in Cardiac Resynchronization Therapy". PMID- 26370368 TI - Effects of Cardiac Resynchronization Therapy on Ventricular Electrical Remodeling in Patients With Heart Failure. AB - Cardiac resynchronization therapy (CRT) reverses structural remodeling of the left ventricle. We investigated whether CRT reverses left-ventricular electrical remodeling.Eighty patients were enrolled and implanted with CRT-devices. Echocardiography and electrocardiography data were obtained from each patient prior to implantation and two years after implantation. At two years after implantation, the patients were classified into a responder group and a non responder group based on echocardiography.Over the next 2 years, 75 patients completed follow-up, and 5 patients had died. Echocardiography results showed that 23 patients could be classified as non-responders and 52 as responders. Larger numbers of non-responders were diagnosed with either ischemic cardiomyopathy (ICM) or nonspecific intraventricular conduction delay (NICD). The intrinsic QRS duration was not changed in responders, patients with dilated cardiomyopathy, or in the patient categories of male and female. However, the intrinsic QRS duration was significantly prolonged in non-responders and patients with ischemic cardiomyopathy (P = 0.041). The mean left ventricular end-diastolic diameter in the responder group was significantly decreased by CRT (P < 0.05), while there was no significant change in intrinsic QRS duration.While CRT does not reduce the intrinsic QRS duration, it can delay negative ventricular electrical remodeling. Continuous CRT is necessary. PMID- 26370369 TI - Head-Up Tilt. AB - Autonomic dysfunction has been associated with paroxysmal atrial fibrillation (PAF). The head-up tilt test (HUTT) is an important diagnostic tool for autonomic dysfunction. The aim of this study was to examine atrial fibrillation recurrence after RFCA by performing HUTT. A total of 488 consecutive patients with PAF who underwent RFCA were prospectively enrolled. HUTT was positive in 154 (31.6%) patients after a mean follow-up of 22.7 +/- 3.5 months, and 163 (33.4%) had a recurrence. HUTT positive was significantly higher in PAF patients with recurrence compared to those without (68 (41.7%) versus 86 (26.5%), P < 0.001). Multivariate Cox regression analysis revealed that HUTT positive (HR: 1.96; 95% CI: 1.49-2.48, P < 0.001), left atrial diameter (HR: 1.77; 95%CI: 1.15-2.11, P = 0.004), AF duration (HR: 1.27; 95%CI: 0.98-1.83, P = 0.014), and sleep apnea (HR: 1.02; 95%CI: 0.81-1.53, P = 0.032) were independent predictors of clinical recurrence after RFCA. The success rate of ablation was 70.4% in patients in the HUTT negative group compared with 58.4% in patients in the HUTT positive group (log-rank P = 0.006). Patients with a positive headup tilt test were at an increased risk of AF recurrence after catheter ablation. Our results suggest that HUTT was a significant predictor for AF recurrence after catheter ablation for PAF. PMID- 26370370 TI - Impact of Right Ventricular Geometry on Mitral Regurgitation After Transcatheter Closure of Atrial Septal Defect. AB - Worsening of mitral regurgitation (MR) is sometimes observed after closure of an atrial septal defect (ASD). However, since the mechanism of this deterioration remains unclear, the aim of our study was to investigate the effect of left (LV) and right ventricular (RV) geometry on MR after transcatheter closure of ASD.We studied 27 patients with ASD who underwent transcatheter closure. Echocardiography was performed before and 6 +/- 2 months after the procedure. In addition to conventional echocardiographic parameters, full volume data of the whole LV and RV heart was obtained with 3-dimensional echocardiography. MR was quantified by measuring the width of the vena contracta, and was graded as mild (< 3.0 mm), moderate (3.0 to 6.9 mm), or severe (>= 7.0 mm).Ten patients (37%) were classified as having worsening MR and the remaining 17 (63%) as not having worsening MR. The two groups showed similar baseline characteristics, except for patients with worsening MR being more likely to be older (P = 0.009) and having a larger left-to-right shunt of pulmonary and systemic blood flow ratio (P = 0.02). It is noteworthy that the horizontal-to-vertical ratio of basal-RV at end-systole for patients with worsening MR was significantly smaller than that for patients without worsening MR (1.0 +/- 0.2 versus 1.4 +/- 0.2, P < 0.0001). Furthermore, multivariate analysis showed that the horizontal-to-vertical ratio of basal-RV at end-systole was the independent predictor of worsening MR during follow-up (P < 0.001).RV geometry may affect MR after closure of ASD. The pre-operative horizontal-to-vertical ratio of basal-RV is considered useful for predicting worsening of MR after closure of ASD. PMID- 26370371 TI - Accuracy of Late Gadolinium Enhancement - Magnetic Resonance Imaging in the Measurement of Left Atrial Substrate Remodeling in Patients With Rheumatic Mitral Valve Disease and Persistent Atrial Fibrillation. AB - The aim of this study was to provide a histopathological validation of cardiac late gadolinium enhancement (LGE) magnetic resonance imaging (MRI) for the assessment of left atrial (LA) substrate remodeling (SRM) in patients with rheumatic mitral valve disease and persistent atrial fibrillation (AF).Adult patients with rheumatic mitral valve disease and persistent AF undergoing open heart surgery for mitral valve replacement were enrolled. Both two-dimensional (2D) sections and 3-dimensional (3D) full-volume LGE-MRI with different signal intensities were performed preoperatively to determine the extent of LA-SRM. Tissue samples were obtained intraoperatively from the LA roof and posterior lateral wall for pathological validation with Masson trichrome staining and immunostaining for collagen type I/III deposition. A linear regression model was used to determine the relationship between MRI-derived LA-SRM parameters and pathological results.Between February 2013 and March 2014, we successfully acquired LA tissue samples from 22 patients (13 men), with a mean age of 47 +/- 8 years. All patients had rheumatic mitral valve stenosis, with a mean effective orifice area of 0.9 +/- 0.2 cm(2) on echocardiography and a mean LA volume of 235 +/- 85 mL on 3D-MRI. Multiple moderate linear associations were noted between the pathological results and LGE-MRI-derived LA-SRM parameters, with correlation indices (r(2)) of 0.194-0.385.LA-SRM measured by LGE-MRI showed moderate agreement with LA pathology in patients with rheumatic valve disease and persistent AF. PMID- 26370372 TI - An Experience of Landiolol Use for an Advanced Heart Failure Patient With Severe Hypotension. AB - Tachyarrhythmias such as atrial fibrillation (AF) or atrial flutter (AFL) sometimes invoke life-threatening collapse of hemodynamics in patients with severe heart failure. Recently, landiolol, an ultra-short acting beta1-selective antagonist, has been reported to be safe and useful for the treatment of supraventricular tachyarrhythmias with reduced left ventricular function. Here we report a case of advanced heart failure with severe hypotension who was treated successfully by landiolol for rapid AF. The patient was a 20-year old male with dilated cardiomyopathy. He presented with low output syndrome in spite of optimal medical therapy and was referred to our department to consider ventricular assist device implantation and heart transplantation. Soon after admission, he developed rapid atrial fibrillation at 180 beats per minute (bpm) followed by severe hypotension and liver enzyme elevation. Low dose landiolol at 2 MUg/kg/minute was started because digoxin was not effective. After landiolol administration, his heart rate decreased to 110 bpm, and finally returned to sinus rhythm without hemodynamic deterioration. Intra-aortic balloon pumping was inserted soon after sinus recovery and he was discharged successfully with an implantable left ventricular assist device. PMID- 26370373 TI - Adaptive Servo-Ventilation Has More Favorable Acute Effects on Hemodynamics Than Continuous Positive Airway Pressure in Patients With Heart Failure. AB - Adaptive servo-ventilation (ASV) has been attracting attention as a novel respiratory support therapy for heart failure (HF). However, the acute hemodynamic effects have not been compared between ASV and continuous positive airway pressure (CPAP) in HF patients.We studied 12 consecutive patients with stable chronic HF. Hemodynamic measurement was performed by right heart catheterization before and after CPAP 5 cmH2O, CPAP 10 cmH2O, and ASV for 15 minutes each.Heart rate, blood pressure, pulmonary capillary wedge pressure (PCWP), and stroke volume index (SVI) were not changed by any intervention. Right atrial pressure significantly increased after CPAP 10 cmH2O (3.6 +/- 3.3 to 6.7 +/- 1.6 mmHg, P = 0.005) and ASV (4.1 +/- 2.6 to 6.8 +/- 1.5 mmHg, P = 0.026). Cardiac index was significantly decreased by CPAP 10 cmH2O (2.3 +/- 0.4 to 1.9 +/ 0.3 L/minute/m(2), P = 0.048), but was not changed by ASV (2.3 +/- 0.4 to 2.0 +/ 0.3 L/ minute/m(2), P = 0.299). There was a significant positive correlation between baseline PCWP and % of baseline SVI by CPAP 10 cmH2O (r = 0.705, P < 0.001) and ASV (r = 0.750, P < 0.001). ASV and CPAP 10 cmH2O had significantly greater slopes of this correlation than CPAP 5 cmH2O, suggesting that patients with higher PCWP had a greater increase in SVI by ASV and CPAP 10 cmH2O. The relationship between baseline PCWP and % of baseline SVI by ASV was shifted upwards compared to CPAP 10 cmH2O. Furthermore, based on the results of a questionnaire, patients accepted CPAP 5 cmH2O and ASV more favorably compared to CPAP 10 cmH2O.ASV had more beneficial effects on acute hemodynamics and acceptance than CPAP in HF patients. PMID- 26370374 TI - Rivaroxaban Inhibits Angiotensin II-Induced Activation in Cultured Mouse Cardiac Fibroblasts Through the Modulation of NF-kappaB Pathway. AB - Cell migration, proliferation, and differentiation of cardiac fibroblasts (CFs) play a central role in cardiac fibrosis. Factor Xa (FXa)-dependent protease activated receptor (PAR)-1 and PAR-2 have been reported as important targets in proinflammatory and fibroproliferative diseases. From this viewpoint, we aimed to investigate whether treatment of rivaroxaban, an approved oral direct FXa inhibitor, attenuates functional changes in angiotensin (Ang) II-induced mouse CFs.Confluent cultured mouse CFs were pretreated with or without rivaroxaban. Ang II-induced cell migration was decreased by 73% in rivaroxaban induced cells. Rivaroxaban inhibited Ang II-induced cell proliferation by 27% at 0.01 MUg/ mL, 69% at 0.1 MUg/mL, 71% at 1 MUg/mL, and 69% at 5 MUg/mL. In mouse cytokine array measuring 40 cytokines, the productions of interleukin-16, TIMP-1, and tumor necrosis factor-alpha (TNF-alpha) were significantly reduced with 0.1 MUg/mL of rivaroxaban pretreatment (all P < 0.05). TIMP-1 levels in the culture supernatant measured by ELISA were also decreased by rivaroxaban pretreatment in Ang II induced CFs (35% decrease at 0.01 MUg/mL, 47% at 0.1 MUg/mL, 47% at 1 MUg/mL, and 57% at 5 MUg/mL). In the dual reporter assay analysis, rivaroxaban inhibited various inflammatory signal pathways, including the nuclear factor-kappa B (NF kappaB), active protein-1 (AP-1), and mitogen-activated protein kinase (MAPK) pathways (decreases of 82%, 78%, and 75%, respectively).These data suggest that rivaroxaban inhibits Ang II-induced functional activation in cultured mouse CFs via inhibiting NF-kappaB and MAPK/AP-1 signaling pathways, which may be a possible target of heart failure, through the antifibrotic and anti-inflammatory efficacy of rivaroxaban in Ang II-stimulated cardiac fibroblasts. PMID- 26370375 TI - KCNN3 SNP rs13376333 on Chromosome 1q21 Confers Increased Risk of Atrial Fibrillation. AB - To investigate the relationship between KCNN3 SNP (single-nucleotide polymorphism) rs13376333 and risk of atrial fibrillation (AF) and to provide evidence for prevention and treatment for AF.The PubMed, Embase, OVID, Cochrane library, CNKI, and Wan Fang databases were searched to identify studies on the relationship between KCNN3 SNP rs13376333 polymorphism and atrial fibrillation. Two authors performed independent article reviews and study quality assessment using the Newcastle-Ottawa Scale (NOS) checklist.Seven studies involving 24,339 individuals were included in the meta-analysis. The overall combined OR of rs13376333 polymorphism was observed for both lone AF (OR: 1.58 [95%CI: 1.37 to 1.82]; P < 0.001; I(2) = 47.0%) and total AF (OR: 1.33 [95%CI: 1.14 to 1.54]; P < 0.001; I(2) = 0). Further, when stratified by ethnicity, control sources, sample sizes, and genotyping method, similar results were observed in both subgroups. Sensitivity analysis revealed that the source of control was the source of the heterogeneity for lone AF. Omission of any single study had little effect on the combined risk estimate. No evidence of publication bias was found.This meta analysis suggests that KCNN3 SNP rs13376333 polymorphism significantly increases the risk of lone AF and total AF, which suggests the rs13376333 polymorphism of the KCNN3 gene may play an important role in the pathogenesis of AF. PMID- 26370376 TI - Reply to Letter Regarding Article, "Improvement of Cardiac Function by Increasing Stimulus Strength during Left Ventricular Pacing in Cardiac Resynchronization Therapy". PMID- 26370377 TI - Recurrent miscarriage is associated with the dopamine receptor (DRD2) genotype. AB - The purpose of this research is to compare the prevalence of dopamine receptor D2 polymorphisms in women with recurrent miscarriage (RM) and healthy patients. Fifty-four women were enrolled in this case-control study. We performed DNA extraction of peripheral blood, followed by polymerase chain reaction to confirm single-strand polymorphisms and to sequence two polymorphisms: polymorphism 1 (rs6275) and polymorphism 2 (rs6277) in exon 7 of the dopamine receptor D2 (DRD2). The frequency of DRD2 polymorphism 2 (rs6277) was increased in the subjects with RM. An analysis of the DRD2 genotypes demonstrated an odds ratio of 2.37 (1.05-5.36, 95% confidence interval) for the polymorphism 2 (rs6277) in RM. The mean of the serum prolactin level was higher in the patients with RM (12.5 ng/ml) than in healthy women (8.1 ng/ml) p = 0.03. An excess homozygosity of the DRD2 polymorphism suggests a genetic predisposition to RMs, which could result in a mild serum prolactin increase. Thus, because of the potential role of prolactin in reproductive regulation, this polymorphism could play an important role in early pregnancy implantation and pregnancy maintenance. PMID- 26370378 TI - Immigrant Caregivers of Young Children: Oral Health Beliefs, Attitudes, and Early Childhood Caries Knowledge. AB - The incidence of early childhood caries (ECC) is a global public health concern. The oral health knowledge of a caregiver can affect a child's risk for developing ECC. An exploratory study of the oral health knowledge and behaviors among caregivers of children 6 years of age and younger was conducted with a convenience sample of adults (n = 114) enrolled in English language or high school equivalency examination courses. The majority of study participants were born in Asia (47 %). Other birth regions included South America (16 %), Caribbean (16 %), Africa (10 %), and Central America (6 %). Study findings showed caregivers with low oral health knowledge were more likely to engage in behaviors that increase a child's risk for developing ECC. A statistically significant relationship was found between participants' rating of their child's dental health as poor and the belief that children should not be weaned from the nursing bottle by 12 months of age (P = 0.002), brushing should not begin upon tooth eruption (P = 0.01), and fluoride does not strengthen teeth and prevent dental caries (P = 0.005). Subjects who pre-chewed their child's food also exhibited behaviors including sharing eating utensils or a toothbrush with their child (P < 0.001). Additional caregiver behaviors included providing their child with a bottle containing cariogenic liquids in a crib (P < 0.001). As a result of this research, it is pertinent that culturally sensitive oral health promotion programs are developed and implemented to raise awareness and reduce the risk of dental disease among immigrant populations. PMID- 26370379 TI - Imbalance between the expression dosages of X-chromosome and autosomal genes in mammalian oocytes. AB - Oocytes have unique characteristics compared with other cell types. In mouse and human oocytes, two X chromosomes are maintained in the active state. Previous microarray studies have shown that the balance of the expression state is maintained in haploid oocytes. Here, we investigated transcripts using RNA sequence technology in mouse and human oocytes. The median expression ratio between X chromosome and autosomal genes (X:A) in immature mouse oocytes increased as the gene expression levels increased, reaching a value of 1. However, the ratio in mature oocytes was under 1 for all expression categories. Moreover, we observed a markedly low ratio resulting from the bimodal expression patterns of X-linked genes. The low X:A expression ratio in mature oocyte was independent of DNA methylation. While mature human oocytes exhibited a slightly low X:A expression ratio, this was the result of the skewed high frequency of lowly expressed X-linked genes rather than the bimodal state. We propose that this imbalance between the expression dosages of X-chromosome and autosomal genes is a feature of transcripts in mammalian oocytes lacking X-chromosome inactivation. PMID- 26370381 TI - Peak Plantar Shear and Pressure and Foot Ulcer Locations: A Call to Revisit Ulceration Pathomechanics. PMID- 26370383 TI - Complete chloroplast genome sequence of Fritillaria unibracteata var. wabuensis based on SMRT Sequencing Technology. AB - Fritillaria unibracteata var. wabuensis is an important medicinal plant used for the treatment of cough symptoms related to the respiratory system. The chloroplast genome of F. unibracteata var. wabuensis (GenBank accession no. KF769142) was assembled using the PacBio RS platform (Pacific Biosciences, Beverly, MA) as a circle sequence with 151 009 bp. The assembled genome contains 133 genes, including 88 protein-coding, 37 tRNA, and eight rRNA genes. This genome sequence will provide important resource for further studies on the evolution of Fritillaria genus and molecular identification of Fritillaria herbs and their adulterants. This work suggests that PacBio RS is a powerful tool to sequence and assemble chloroplast genomes. PMID- 26370382 TI - Subclinical Atherosclerosis Is Inversely Associated With Gray Matter Volume in African Americans With Type 2 Diabetes. AB - OBJECTIVE: Relative to European Americans, African Americans manifest lower levels of computed tomography-based calcified atherosclerotic plaque (CP), a measure of subclinical cardiovascular disease (CVD). Potential relationships between CP and cerebral structure are poorly defined in the African American population. We assessed associations among glycemic control, inflammation, and CP with cerebral structure on MRI and with cognitive performance in 268 high-risk African Americans with type 2 diabetes. RESEARCH DESIGN AND METHODS: Associations among hemoglobin A1c (HbA1c), C-reactive protein (CRP), and CP in coronary arteries, carotid arteries, and the aorta with MRI volumetric analysis (white matter volume, gray matter volume [GMV], cerebrospinal fluid volume, and white matter lesion volume) were assessed using generalized linear models adjusted for age, sex, African ancestry proportion, smoking, BMI, use of statins, HbA1c, hypertension, and prior CVD. RESULTS: Participants were 63.4% female with mean (SD) age of 59.8 years (9.2), diabetes duration of 14.5 years (7.6), HbA1c of 7.95% (1.9), estimated glomerular filtration rate of 86.6 mL/min/1.73 m(2) (24.6), and coronary artery CP mass score of 215 mg (502). In fully adjusted models, GMV was inversely associated with coronary artery CP (parameter estimate [beta] -0.47 [SE 0.15], P = 0.002; carotid artery CP (beta -1.92 [SE 0.62], P = 0.002; and aorta CP [beta -0.10 [SE 0.03] P = 0.002), whereas HbA1c and CRP did not associate with cerebral volumes. Coronary artery CP also associated with poorer global cognitive function on the Montreal Cognitive Assessment. CONCLUSIONS: Subclinical atherosclerosis was associated with smaller GMV and poorer cognitive performance in African Americans with diabetes. Cardioprotective strategies could preserve GMV and cognitive function in high-risk African Americans with diabetes. PMID- 26370384 TI - The role of an occlusal template during the placement of preformed metal crowns in children under general anaesthesia: a randomised control trial. AB - AIM: This aim was to evaluate preformed metal crowns (PMC) placed under general anaesthesia using an occlusal template in comparison to crowns placed without the use of a template. METHODOLOGY: CONSORT protocols were followed in the design of the study. A total of 60 children between 4-7 years requiring pulpotomy and PMC for all primary molars met the inclusion criteria for this study. The control group comprised patients for whom the PMC were placed without the use of an occlusal template, while in the test group crowns were placed using a polyvinyl siloxane occlusal template. Patients were followed up at 24 h, 7 days, 3 and 6 months. The time taken for the placement of crowns, instances of post-operative discomfort, success or failure of the pulp therapy and loss of any crowns were compared between the groups. RESULTS: The mean time taken for completion of the procedure in the control group was significantly greater than the template group (t = 2.566, p = 0.013). Significantly fewer patients in the template group reported symptoms of discomfort or high points at the 24-h recall; however, these differences were not significant at the 1-week, 3- or 6-month recall. CONCLUSION: The use of an occlusal template for the placement of multiple PMC under general anaesthesia reduces the time taken for their placement and reduces the incidence of immediate post-operative discomfort. PMID- 26370380 TI - Mediterranean Diet, Retinopathy, Nephropathy, and Microvascular Diabetes Complications: A Post Hoc Analysis of a Randomized Trial. AB - OBJECTIVE: To date no clinical trials have evaluated the role of dietary patterns on the incidence of microvascular diabetes complications. We hypothesized that a nutritional intervention based on the Mediterranean diet (MedDiet) would have greater protective effect on diabetic retinopathy and nephropathy than a low-fat control diet. RESEARCH DESIGN AND METHODS: This was a post hoc analysis of a cohort of patients with type 2 diabetes participating in the PREvencion con DIeta MEDiterranea (PREDIMED) study, a multicenter randomized nutritional intervention trial conducted in a population at high cardiovascular risk. Individuals with type 2 diabetes who were free of microvascular complications at enrollment (n = 3,614, aged 55-80 years) were randomly assigned to one of three dietary interventions: MedDiet supplemented with extravirgin olive oil (MedDiet+EVOO), MedDiet supplemented with mixed nuts (MedDiet+Nuts), or a low-fat control diet. Two independent outcomes were considered: new onset of diabetic retinopathy and nephropathy. Hazard ratios (HRs) were calculated using multivariable-adjusted Cox regression. RESULTS: During a median follow-up of 6.0 years, we identified 74 new cases of retinopathy and 168 of nephropathy. Compared with the control diet, multivariable-adjusted HRs for diabetic retinopathy were 0.56 (95% CI 0.32-0.97) for the MedDiet+EVOO and 0.63 (0.35-1.11) for the MedDiet+Nuts. No between-group differences were found for nephropathy. When the yearly updated information on adherence to the MedDiet was considered, the HR for retinopathy in the highest versus the lowest quintile was 0.34 (0.13-0.89; P = 0.001 for trend). No significant associations were found for nephropathy. CONCLUSIONS: A MedDiet enriched with EVOO may protect against diabetic retinopathy but not diabetic nephropathy. PMID- 26370385 TI - SPG5 and multiple sclerosis: clinical and genetic overlap? AB - BACKGROUND: Autosomal recessive (AR) spastic paraplegia type 5 (SPG5) is due to mutations in the CYP7B1 gene, encoding for the cytochrome P450-7B1, responsible for oxysterols 7alpha-hydroxylation. Oxysterol/cholestenoic acids pool plays a role in motor neuron survival and immune response. SPG5 is characterized by white matter abnormalities at brain resonance imaging (MRI). In view of clinical presentation and MRI findings, multiple sclerosis (MS) is a possible differential diagnosis of SPG5. This study aimed to evaluate the frequency of CYP7B1 mutations in patients with MS. METHODS: One hundred and seventeen MS patients with clinical spastic paraplegia or possible AR transmission were selected for the mutational screening. RESULTS: Forty-three patients had primary progressive, 26 relapsing remitting, 26 secondary progressive, and 22 relapsing progressive MS clinical course. No CYP7B1 homozygous mutations were identified. Two novel variants and one pathogenic mutation were found at heterozygous state. CONCLUSIONS: The two novel variants cosegregated with pyramidal signs and autoimmune diseases suggesting that they might be susceptibility factors. Reduced cytochrome P450-7B1 enzymatic activity could alter the balance among neurotoxic and neuroprotective oxysterols promoting motor neuron degeneration and/or immune response. PMID- 26370386 TI - Enhancing isobutyric acid production from engineered Acidithiobacillus ferrooxidans cells via media optimization. AB - The chemolithoautotrophic bacterium Acidithiobacillus ferrooxidans has previously been genetically modified to produce isobutyric acid (IBA) from carbon dioxide while obtaining energy from the oxidation of ferrous iron. Here, a combinatorial approach was used to explore the influence of medium composition in both batch and chemostat cultures in order to improve IBA yields (g IBA/mol Fe(2+)) and productivities (g IBA/L/d). Medium pH, ferrous concentration (Fe(2+)), and inclusion of iron chelators all had positive impact on the IBA yield. In batch experiments, gluconate was found to be a superior iron chelator because its use resulted in smaller excursions in pH. In batch cultures, IBA yields decreased linearly with increases in the final effective Fe(3+) concentrations. Chemostat cultures followed similar trends as observed in batch cultures. Specific cellular productivities were found to be a function of the steady state ORP (Oxidation reduction potential) of the growth medium, which is primarily determined by the Fe(3+) to Fe(2+) ratio. By operating at low ORP, chemostat cultures were able to achieve volumetric productivities as high as 3.8 +/- 0.2 mg IBA/L/d which is a 14 fold increase over the previously reported value. PMID- 26370388 TI - Answer to the Letter to the Editor of Guoping Liao et al. concerning "Comparison of unilateral versus bilateral pedicle screw fixation in lumbar interbody fusion: a meta-analysis" by W. Ding et al. (2014) Eur Spine J 23(2):395-403. PMID- 26370389 TI - Decision-making and patient's expectations. PMID- 26370390 TI - Unusual presentation of vertebral endplate Modic changes in congenital scoliosis associated with pain: a report of two cases. AB - Congenital scoliosis is not normally associated with pain in young children. We are presenting two cases of young patients with congenital scoliosis and moderate to severe pain. There were no spinal cord abnormalities found in these patients. The magnetic resonance imaging and CT scan revealed disc degeneration with Modic changes at the apex of the congenital scoliosis. We hypothesized that the mechanical instability resulting from poor spinal element formations associated with congenital scoliosis was responsible for causing the disc degeneration and endplate changes. Modic changes have been reported to be associated with pain in degenerative conditions of the spine. Both patients underwent a posterior spinal fusion and instrumentation, which relieved their pain immediately. PMID- 26370392 TI - Getting Down to Earth: The Renaissance of Catalysis with Abundant Metals. PMID- 26370391 TI - Comparative genomic analyses of freshly isolated Giardia intestinalis assemblage A isolates. AB - BACKGROUND: The diarrhea-causing protozoan Giardia intestinalis makes up a species complex of eight different assemblages (A-H), where assemblage A and B infect humans. Comparative whole-genome analyses of three of these assemblages have shown that there is significant divergence at the inter-assemblage level, however little is currently known regarding variation at the intra-assemblage level. We have performed whole genome sequencing of two sub-assemblage AII isolates, recently axenized from symptomatic human patients, to study the biological and genetic diversity within assemblage A isolates. RESULTS: Several biological differences between the new and earlier characterized assemblage A isolates were identified, including a difference in growth medium preference. The two AII isolates were of different sub-assemblage types (AII-1 [AS175] and AII-2 [AS98]) and showed size differences in the smallest chromosomes. The amount of genetic diversity was characterized in relation to the genome of the Giardia reference isolate WB, an assemblage AI isolate. Our analyses indicate that the divergence between AI and AII is approximately 1 %, represented by ~100,000 single nucleotide polymorphisms (SNP) distributed over the chromosomes with enrichment in variable genomic regions containing surface antigens. The level of allelic sequence heterozygosity (ASH) in the two AII isolates was found to be 0.25-0.35 %, which is 25-30 fold higher than in the WB isolate and 10 fold higher than the assemblage AII isolate DH (0.037 %). 35 protein-encoding genes, not found in the WB genome, were identified in the two AII genomes. The large gene families of variant-specific surface proteins (VSPs) and high cysteine membrane proteins (HCMPs) showed isolate-specific divergences of the gene repertoires. Certain genes, often in small gene families with 2 to 8 members, localize to the variable regions of the genomes and show high sequence diversity between the assemblage A isolates. One of the families, Bactericidal/Permeability Increasing like protein (BPIL), with eight members was characterized further and the proteins were shown to localize to the ER in trophozoites. CONCLUSIONS: Giardia genomes are modular with highly conserved core regions mixed up by variable regions containing high levels of ASH, SNPs and variable surface antigens. There are significant genomic variations in assemblage A isolates, in terms of chromosome size, gene content, surface protein repertoire and gene polymorphisms and these differences mainly localize to the variable regions of the genomes. The large genetic differences within one assemblage of G. intestinalis strengthen the argument that the assemblages represent different Giardia species. PMID- 26370393 TI - Testing a "content meets process" model of depression vulnerability and rumination: Exploring the moderating role of set-shifting deficits. AB - BACKGROUND AND OBJECTIVES: MacCoon and Newman's (2006) "content meets process" model posits that deficits in cognitive control make it difficult to disengage from negative cognitions caused by a negative cognitive style (NCS). The present study examined if the interactive effect of cognitive set-shifting abilities and NCS predicts rumination and past history of depression. METHODS: Participants were 90 previously depressed individuals and 95 never depressed individuals. We administered three laboratory tasks that assess set-shifting: the Wisconsin Card Sorting Task, the Emotional Card-Sorting Task, and the Internal Switch Task, and self-report measures of NCS and rumination. RESULTS: Shifting ability in the context of emotional distractors moderated the association between NCS and depressive rumination. Although previously depressed individuals had more NCS and higher trait rumination relative to never depressed individuals, shifting ability did not moderate the association between NCS and depression history. LIMITATIONS: The cross-sectional correlational design cannot address the causal direction of effects. It is also not clear whether findings will generalize beyond college students. CONCLUSIONS: NCS was elevated in previously depressed individuals consistent with its theoretical role as trait vulnerability to the disorder. Furthermore, NCS may be particularly likely to trigger rumination among individuals with poor capacity for cognitive control in the context of emotional distraction. PMID- 26370394 TI - Attentional blink impairment in social anxiety disorder: Depression comorbidity matters. AB - BACKGROUND AND OBJECTIVES: Difficulties with attentional control have long been thought to play a key role in anxiety and depressive disorders. However, the nature and extent of attentional control difficulties in social anxiety disorder (SAD) are not yet well understood. The current study was designed to assess whether attentional control for non-emotional information is impaired in SAD when taking comorbid depression into account.. METHODS: Individuals with SAD and healthy controls (HCs) were administered an attentional blink (AB) task in which they identified number targets in a rapid serial visual presentation stream of letters. RESULTS: Individuals with SAD and current comorbid depression exhibited reduced accuracy to identify a target that fell within the AB window after the presentation of a first target compared to individuals with SAD without current comorbid depression, as well as to HCs. The latter two groups did not differ from each other, and the three groups did not differ in accuracy for the second target when it was presented after the AB window. LIMITATIONS: Although we included two clinical groups and the sample size for the non-comorbid SAD group was large, the comorbid SAD group was relatively small. CONCLUSIONS: These results suggest that impaired attentional control among individuals with SAD may be limited to those suffering from current comorbid depression.. PMID- 26370395 TI - Asynchronous data acquisition and on-the-fly analysis of dose fractionated cryoEM images by UCSFImage. AB - Newly developed direct electron detection cameras have a high image output frame rate that enables recording dose fractionated image stacks of frozen hydrated biological samples by electron cryomicroscopy (cryoEM). Such novel image acquisition schemes provide opportunities to analyze cryoEM data in ways that were previously impossible. The file size of a dose fractionated image stack is 20-60 times larger than that of a single image. Thus, efficient data acquisition and on-the-fly analysis of a large number of dose-fractionated image stacks become a serious challenge to any cryoEM data acquisition system. We have developed a computer-assisted system, named UCSFImage4, for semi-automated cryo EM image acquisition that implements an asynchronous data acquisition scheme. This facilitates efficient acquisition, on-the-fly motion correction, and CTF analysis of dose fractionated image stacks with a total time of ~60s/exposure. Here we report the technical details and configuration of this system. PMID- 26370396 TI - The operating room case-mix problem under uncertainty and nurses capacity constraints. AB - Surgery is one of the key functions in hospitals; it generates significant revenue and admissions to hospitals. In this paper we address the decision of choosing a case-mix for a surgery department. The objective of this study is to generate an optimal case-mix plan of surgery patients with uncertain surgery operations, which includes uncertainty in surgery durations, length of stay, surgery demand and the availability of nurses. In order to obtain an optimal case mix plan, a stochastic optimization model is proposed and the sample average approximation method is applied. The proposed model is used to determine the number of surgery cases to be weekly served, the amount of operating rooms' time dedicated to each specialty and the number of ward beds dedicated to each specialty. The optimal case-mix selection criterion is based upon a weighted score taking into account both the waiting list and the historical demand of each patient category. The score aims to maximizing the service level of the operating rooms by increasing the total number of surgery cases that could be served. A computational experiment is presented to demonstrate the performance of the proposed method. The results show that the stochastic model solution outperforms the expected value problem solution. Additional analysis is conducted to study the effect of varying the number of ORs and nurses capacity on the overall ORs' performance. PMID- 26370397 TI - Resistance gene analogs involved in tolerant cassava--geminivirus interaction that shows a recovery phenotype. AB - The current literature describes recovery from virus-induced symptoms as a RNA silencing defense, but immunity-related genes, including the structurally specific resistance gene analogs (RGAs) that may play a key role in tolerance and recovery is not yet reported. In this study, the transcriptome data of tolerant cassava TME3 (which exhibits a recovery phenotype) and susceptible cassava T200 infected with South African cassava mosaic virus were explored for RGAs. Putative resistance protein analogs (RPAs) with amide-like indole-3-acetic acid-Ile-Leu Arg (IAA-ILR) and leucine-rich repeat (LRR)-kinase conserved domains were unique to TME3. Common responsive RPAs in TME3 and T200 were the dirigent-like protein, coil-coil nucleotide-binding site (NBS) and toll-interleukin-resistance, disease resistance zinc finger chromosome condensation-like protein (DZC), and NBS apoptosis repressor with caspase recruitment (ARC)-LRR domains. Mutations in RPAs in the MHD motif of the NBS-ARC2 subdomain associated with the recovery phase in TME3 were observed. Additionally, a cohort of 25 RGAs mined solely during the recovery process in TME3 was identified. Phylogenetic and expression analyses support that diverse RGAs are differentially expressed during tolerance and recovery. This study reveals that in cassava, a perennial crop, RGAs participate in tolerance and differentially accumulate during recovery as a complementary defense mechanism to natural occurring RNA silencing to impair viral replication. PMID- 26370398 TI - Different disease subtypes with distinct clinical expression in familial Mediterranean fever: results of a cluster analysis. AB - OBJECTIVE: The aim of this study was to evaluate whether there are clinical subgroups that may have different prognoses among FMF patients. METHODS: The cumulative clinical features of a large group of FMF patients [1168 patients, 593 (50.8%) male, mean age 35.3 years (s.d. 12.4)] were studied. To analyse our data and identify groups of FMF patients with similar clinical characteristics, a two step cluster analysis using log-likelihood distance measures was performed. For clustering the FMF patients, we evaluated the following variables: gender, current age, age at symptom onset, age at diagnosis, presence of major clinical features, variables related with therapy and family history for FMF, renal failure and carriage of M694V. RESULTS: Three distinct groups of FMF patients were identified. Cluster 1 was characterized by a high prevalence of arthritis, pleuritis, erysipelas-like erythema (ELE) and febrile myalgia. The dosage of colchicine and the frequency of amyloidosis were lower in cluster 1. Patients in cluster 2 had an earlier age of disease onset and diagnosis. M694V carriage and amyloidosis prevalence were the highest in cluster 2. This group of patients was using the highest dose of colchicine. Patients in cluster 3 had the lowest prevalence of arthritis, ELE and febrile myalgia. The frequencies of M694V carriage and amyloidosis were lower in cluster 3 than the overall FMF patients. Non-response to colchicine was also slightly lower in cluster 3. CONCLUSION: Patients with FMF can be clustered into distinct patterns of clinical and genetic manifestations and these patterns may have different prognostic significance. PMID- 26370399 TI - Successful use of rituximab in refractory cardiac sarcoidosis. PMID- 26370401 TI - Is Social Status Related to Internet Pornography Use? Evidence from the Early 2000s in the United States. AB - While most studies on Internet pornography focus on individual's psychological characteristics, few have explored how social status itself is associated with Internet pornography use. As the Internet is becoming increasingly prevalent, online behaviors may have started to reflect the inequalities of the offline world. This study tested whether lower social status was associated with fewer sexual intercourse opportunities, and whether this led to higher likelihood of using Internet pornography as an alternative means of sexual release. To test the theory, I used the nationally representative sample of the General Social Survey of the U.S. between 2000 and 2004, with missing data handled by chained multiple imputation. The analyses found that lower income, longer working length, being unemployed, or a laborer in the social class strata were associated with fewer sexual intercourse opportunities as measured by three variables: marital status, the number of sex partners, and sex frequency. Lower income, less education, and longer working length were also associated with higher odds of using Internet pornography in the past 30 days, but only income was partially mediated by marital status. Social status was associated with Internet pornography use and sexual intercourse opportunities independently. The comparison of Internet pornography with the traditional X-rated movie found the unique features of Internet pornography use absent for X-rated movie. PMID- 26370400 TI - Lower omega-3 fatty acids are associated with the presence of anti-cyclic citrullinated peptide autoantibodies in a population at risk for future rheumatoid arthritis: a nested case-control study. AB - OBJECTIVE: The aim of this study was to investigate omega-3 fatty acid (FA) supplement use and omega-3 FAs in erythrocyte membranes [omega-3 FA % in erythrocyte membranes (RBC)] and their association with anti-CCP autoantibodies in a population without RA, but who are at genetic risk for RA. METHODS: The multicentre Studies of the Etiology of RA (SERA) cohort includes RA-free subjects who are first-degree relatives of RA probands or are enriched with the HLA-DR4 allele. In a nested case-control study, 30 SERA cases were identified who were anti-CCP2 antibody positive. We further identified 47 autoantibody negative controls, frequency matched to cases on age at study visit, sex, race and study site. Anti-CCP2 status, self-reported omega-3 FA supplement use and omega-3 FA % in RBCs were obtained from a single visit. RESULTS: Anti-CCP2 positive cases were less likely than controls to report omega-3 FA supplement use (odds ratio: 0.14; 95% CI 0.03, 0.68). In addition, the likelihood of anti-CCP2 positivity was inversely associated with total omega-3 FA % in RBCs (odds ratio: 0.47; 95% CI 0.24, 0.92, for a s.d. increase). CONCLUSION: The inverse association between anti-CCP2 positivity and self-reported omega-3 FA supplement use and omega-3 FA % in RBCs suggests that omega-3 FAs may protect against the development of RA related autoimmunity in pre-clinical RA. PMID- 26370402 TI - Erectile Dysfunction and Sexual Hormone Levels in Men With Obstructive Sleep Apnea: Efficacy of Continuous Positive Airway Pressure. AB - In this study, the prevalence of erectile dysfunction (ED) and serum sexual hormone levels were evaluated in men with obstructive sleep apnea (OSA). In these patients, the efficacy of continuous positive airway pressure (CPAP) was determined. The 207 men (mean age 44.0 +/- 11.1 years) enrolled in the study were stratified within four groups based on their apnea-hypopnea index score: simple snoring (n = 32), mild OSA (n = 29), moderate OSA (n = 38), and severe OSA (n = 108). The International Index of Erectile Dysfunction-5 (IIEF-5) score was obtained from each patient, and blood samples for the analysis of sexual hormones (prolactin, luteotropin, follicle-stimulating hormone, estradiol, progestin, and testosterone) were drawn in the morning after polysomnography. The IIEF-5 test and serum sexual hormone measurements were repeated after 3 months of CPAP treatment in 53 men with severe OSA. The prevalence of ED was 60.6 % in OSA patients overall and 72.2 % in those with severe OSA. Compared with the simple snoring group, patients with severe OSA had significantly lower testosterone levels (14.06 +/- 5.62 vs. 17.02 +/- 4.68, p = .018) and lower IIEF-5 scores (16.33 +/- 6.50 vs. 24.09 +/- 1.94, p = .001). The differences in the other sexual hormones between groups were not significant. After 3 months of CPAP treatment, there were no significant changes in sexual hormone levels, but the IIEF-5 score had improved significantly (18.21 +/- 4.05 vs. 19.21 +/- 3.86, p = .001). Severe OSA patients have low testosterone concentration and high ED prevalence. IIEF-5 scores increased significantly after CPAP treatment, but there was no effect on serum testosterone levels. PMID- 26370404 TI - Discriminating Coercive from Sadomasochistic Sexuality. AB - Sadomasochistic (SM) sexual interest is reported by a wide range of individuals. Within the sex offender literature, the presence of SM interest is often viewed as a herald of criminal sexual behavior; however, research indicates that SM interests are not predictive of coercive sexual behavior. In the current study, we measured a range of sexual fantasies and behaviors, and then applied cluster analyses to determine (1) if individuals endorsed elevated SM interests also endorsed coercive fantasies and, (2) to explore cluster membership correlates using measures of sensation seeking, externalizing and antisocial behaviors, attitudes toward rape, and empathic capacity. A total of 550 participants were recruited through a variety of on-line discussion areas. A four cluster solution best fit the data with distinct clusters observed for those endorsing SM behaviors and those reporting coercive sexual behavior. Additional analyses revealed greater endorsement of victim blaming attitudes and lower empathic concern among members of the coercive sexual behavior cluster. Elevated sensation seeking and externalizing behaviors were reported by members of clusters marked by SM and coercive sexual behavior. Results provide further support for the differentiation between SM and coercive sexual behaviors as representative of individuals with divergent attitudes, traits, and behaviors. PMID- 26370403 TI - Body Dissatisfaction in a Diverse Sample of Young Men Who Have Sex With Men: The P18 Cohort Study. AB - Young men who have sex with men (YMSM) may be at greater risk for body dissatisfaction, compared to their heterosexual peers. However, differences within YMSM populations are understudied, precluding the identification of YMSM who are at greatest risk. This study examined body dissatisfaction in a racially/ethnically diverse sample of YMSM ages 18-19 in New York City. Using cross-sectional data from the baseline visit of a longitudinal cohort study of YMSM (N = 591), body dissatisfaction was assessed using the Male Body Attitudes Scale. Three outcomes were modeled using linear regression: (1) overall body dissatisfaction, (2) muscularity dissatisfaction, and (3) body fat dissatisfaction. Covariates in the models included race/ethnicity, sexual orientation, BMI, gay community affiliation, and internalized homonegativity. White YMSM experienced greater body dissatisfaction across the three models. Internalized homonegativity was a statistically significant predictor of dissatisfaction across the three models, though its association with body dissatisfaction was relatively small. The findings point to future avenues of research, particularly qualitative research to explore demographic and cultural nuances in body attitudes among YMSM. PMID- 26370405 TI - Rupture of an Artificial Urinary Sphincter Secondary to Use of a Vacuum Pump for Erectile Dysfunction. PMID- 26370406 TI - Acute respiratory distress syndrome: does histology matter? AB - Kao et al. have reported in Critical Care the histological findings of 101 patients with acute respiratory distress syndrome (ARDS) undergoing open lung biopsy. Diffuse alveolar damage (DAD), the histological hallmark of ARDS, was present in only 56.4% of cases. The presence of DAD was associated with higher mortality. Evidence from this and other studies indicates that the clinical criteria for the diagnosis of ARDS identify DAD in only about half of the cases. On the contrary, there is evidence that the clinical course and outcome of ARDS differs in patients with DAD and in patients without DAD. The discovery of biomarkers for the physiological (increased alveolocapillary permeability) or histological (DAD) hallmarks of ARDS is thus of paramount importance. PMID- 26370407 TI - [Synovial tumors and tumor-like lesions]. AB - Synovial tumors comprise a variety of lesions, including those with benign and aggressive neoplastic changes as well as inflammatory causes. In this article we focus on neoplastic tumors. Synovial tumors with other etiologies, such as sarcoidosis, granuloma, synovitis, or gouty arthritis, are not dealt with here. Through a precise differentiation between these disease entities can an optimization of treatment be achieved. PMID- 26370408 TI - Impact of Continuous Positive Airway Pressure on Cardiovascular Risk Factors in High-Risk Patients. AB - Cardiovascular disease remains the leading cause of morbidity and mortality in developed countries. Obstructive sleep apnea is a highly prevalent condition characterized by repetitive upper airway collapse during sleep. A large body of evidence suggests that obstructive sleep apnea is associated with the development of cardiovascular disease and increased cardiovascular morbidity and mortality. Continuous positive airway pressure (CPAP) is the current gold standard for the treatment of obstructive sleep apnea. CPAP devices maintain upper airway patency using a pneumatic splint, thereby ameliorating the repetitive deoxygenation and reoxygenation characteristic of sleep in obstructive sleep apnea patients. Accumulating evidence suggests that CPAP treatment may lead to a reduction in blood pressure. Limited evidence also suggests that CPAP therapy may modulate glucose metabolism, serum cholesterol levels, and inflammatory biomarkers. Thus, CPAP treatment may be associated with cardiovascular risk factor modification in patients with obstructive sleep apnea, who are often obese and at an increased risk of developing cardiovascular disease. This review updates the knowledge on the effects of CPAP on cardiovascular risk factors from recently published randomized trials. PMID- 26370410 TI - Dissecting the Rev-erbalpha Cistrome and the Mechanisms Controlling Circadian Transcription in Liver. AB - Circadian clocks maintain whole-body metabolic homeostasis by coordinating rhythmic gene expression in multiple tissues. Core clock regulators sustain their own oscillation and confer expression rhythmicity on clock-controlled genes (CCGs). Our unbiased examination of enhancer RNA (eRNA) transcription around the clock in mouse liver identified functional enhancers of circadian genes driven by phase-specific transcription factors (TFs). Rev-erbalpha emerged as a primary driver of circadian enhancers, leading to oscillating gene expression in opposite phases through direct and indirect regulation. Among Rev-erbalpha target genes were core clock components and metabolic CCGs. Oscillation of clock genes was enforced by direct competition between Rev-erbalpha and RORalpha for binding to cognate motifs in the genome, whereas metabolic CCGs were governed by recruitment of the NCoR/HDAC3 complex to enhancers where Rev-erbalpha is tethered by tissue specific TFs. The DNA sequence-mediated competition between Rev-erbalpha and RORalpha ensures consistent clock control across all tissues. In contrast, the tethered binding mechanism is tissue-specific and thus allows Rev-erbalpha to dictate an epigenomic rhythm tailored to the specific need of that tissue. Therefore, discrete modes of recruitment allow Rev-erbalpha to link the clock to cell-specific functions, including metabolism. PMID- 26370409 TI - Resolution of Recombination Intermediates: Mechanisms and Regulation. AB - DNA strand break repair by homologous recombination leads to the formation of intermediates in which sister chromatids are covalently linked. The efficient processing of these joint molecules, which often contain four-way structures known as Holliday junctions, is necessary for efficient chromosome segregation during mitotic division. Because persistent chromosome bridges pose a threat to genome stability, cells ensure the complete elimination of joint molecules through three independent pathways. These involve (1) BLM-Topoisomerase IIIalpha RMI1-RMI2 (BTR complex), (2) SLX1-SLX4-MUS81-EME1 (SLX-MUS complex), and (3) GEN1. The BTR pathway promotes the dissolution of double Holliday junctions, which avoids the formation of crossover products, prevents sister chromatid exchanges, and limits the potential for loss of heterozygosity. In contrast to BTR, the other two pathways resolve Holliday junctions by nucleolytic cleavage to yield crossover and non-crossover products. To avoid competition with BTR, the resolution pathways are restrained until the late stages of the cell cycle. The temporal regulation of the dissolution/resolution pathways is therefore critical for crossover avoidance while also ensuring that all covalent links between chromosomes are resolved before chromosome segregation. PMID- 26370411 TI - Perturbing Chromatin Structure to Understand Mechanisms of Gene Expression. AB - The study of nuclear structure falls between the fields of cell biology and molecular biology and draws on techniques from both fields. In recent years, many exciting advances have been made in these areas, including single-molecule and superresolution imaging and the development of chromosome conformation capture (3C)-based technologies, which have brought the advent of genome-wide analysis of chromatin structure and contacts. However, many questions remain as to the function of nuclear structures, in particular their influence on transcription. Here we describe studies that have directly manipulated nuclear architecture at various levels and thus have clarified the causal influence of structure on transcription. We will also highlight open questions in the field, most notably regarding our understanding of the dynamics and variability in nuclear structure and its influence on gene expression. PMID- 26370412 TI - Development and validation of an epitope prediction tool for swine (PigMatrix) based on the pocket profile method. AB - BACKGROUND: T cell epitope prediction tools and associated vaccine design algorithms have accelerated the development of vaccines for humans. Predictive tools for swine and other food animals are not as well developed, primarily because the data required to develop the tools are lacking. Here, we overcome a lack of T cell epitope data to construct swine epitope predictors by systematically leveraging available human information. Applying the "pocket profile method", we use sequence and structural similarities in the binding pockets of human and swine major histocompatibility complex proteins to infer Swine Leukocyte Antigen (SLA) peptide binding preferences. We developed epitope prediction matrices (PigMatrices), for three SLA class I alleles (SLA-1*0401, 2*0401 and 3*0401) and one class II allele (SLA-DRB1*0201), based on the binding preferences of the best-matched Human Leukocyte Antigen (HLA) pocket for each SLA pocket. The contact residues involved in the binding pockets were defined for class I based on crystal structures of either SLA (SLA-specific contacts, Ssc) or HLA supertype alleles (HLA contacts, Hc); for class II, only Hc was possible. Different substitution matrices were evaluated (PAM and BLOSUM) for scoring pocket similarity and identifying the best human match. The accuracy of the PigMatrices was compared to available online swine epitope prediction tools such as PickPocket and NetMHCpan. RESULTS: PigMatrices that used Ssc to define the pocket sequences and PAM30 to score pocket similarity demonstrated the best predictive performance and were able to accurately separate binders from random peptides. For SLA-1*0401 and 2*0401, PigMatrix achieved area under the receiver operating characteristic curves (AUC) of 0.78 and 0.73, respectively, which were equivalent or better than PickPocket (0.76 and 0.54) and NetMHCpan version 2.4 (0.41 and 0.51) and version 2.8 (0.72 and 0.71). In addition, we developed the first predictive SLA class II matrix, obtaining an AUC of 0.73 for existing SLA DRB1*0201 epitopes. Notably, PigMatrix achieved this level of predictive power without training on SLA binding data. CONCLUSION: Overall, the pocket profile method combined with binding preferences from HLA binding data shows significant promise for developing T cell epitope prediction tools for pigs. When combined with existing vaccine design algorithms, PigMatrix will be useful for developing genome-derived vaccines for a range of pig pathogens for which no effective vaccines currently exist (e.g. porcine reproductive and respiratory syndrome, influenza and porcine epidemic diarrhea). PMID- 26370413 TI - Hierarchical modelling of blood lipids' profile and 10-year (2002-2012) all cause mortality and incidence of cardiovascular disease: the ATTICA study. AB - BACKGROUND: The traditional view on the relationship between lipid biomarkers and CVD risk has changed during the last decade. However, it is not clear whether novel lipid biomarkers are able to confer a better predictability of CVD risk, compared to traditional ones.Under this perspective, the aim of the present work was to evaluate the predictive ability of blood lipids' profile on all cause mortality as well as 10-year incidence of CVD, in a sample of apparently healthy adults of the ATTICA epidemiological study. METHODS: From May 2001 to December 2002, 1514 men and 1528 women (>18 y) without any clinical evidence of any other chronic disease, at baseline, were enrolled. In 2011-12, the 10-year follow-up was performed in 2583 participants (85 % follow-up participation rate). Incidence of fatal or non-fatal CVD was defined according to WHO-ICD-10 criteria. Baseline serum blood lipids' profile (Total-C, HDL-, non HDL-, LDL-cholesterol, triglycerides (TG), apolipoprotein (Apo)A1 and B, and lipoprotein-(a) levels were also measured. RESULTS: The 10-year all-cause mortality rate was 5.7 % for men and 2.0 % for women (p = 0.55). The, 10-year CVD incidence was 19.7 % in men and 11.7 % in women (p < 0.001). Multi-adjusted analysis revealed that TC, non-HDL-C, TG and TG/HDL-C ratio, were independent predictors of all cause mortality (RR per 1 mg/dL or unit (95 % CI): 1.006 (1.000-1.013), 1.006 (1.000-1.013), 1.002 (1.000 1.004), 1.038 (1.001-1.077), respectively). Moreover, TC, HDL-, LDL-, non-HDL cholesterol, TG, apoA1, TC/HDL-C and TG/HDL-C were independently associated with CVD risk. Among all lipid indices the ratio of apoB/apoA1 demonstrated the best correct reclassification ability, followed by non-HDL-C and TC/HDL-C ratio (continuous Net Reclassification Index 26.1 and 21.2 %, respectively). CONCLUSION: Elevated levels of lipid biomarkers are independently associated with all-cause mortality, as well as CVD risk. The ratio of apoB/apoA1, followed by non-HDL-C, demonstrated the best correct classification ability of the developed CVD risk models. PMID- 26370414 TI - Cord pilot trial: update to randomised trial protocol. AB - BACKGROUND: The Cord Pilot Trial aimed to assess the feasibility of conducting a large UK randomised trial to compare the effects of alternative polices for timing of cord clamping (immediate within 20 seconds or deferred after at least 2 minutes) for very preterm birth before 32 weeks gestation. Initial recruitment was from March 2013 to February 2014, phase 2 was from March 2014 to February 2015. This paper updates the pilot trial protocol (Trials 15(1):258, 2014) and presents the changes for phase 2. METHODS: An electronic randomisation system was introduced at three of the eight pilot sites. For follow-up of children, the Parent Report of Children's Abilities--Revised (PARCA-R) will not be used. For children recruited to the trial during phase 2, follow-up at age 2 years (corrected for gestation at birth) will be by parent completed Ages and Stages Questionnaire (Squire J, Ages and Stages Questionnaires (ASQ), 2009) alone unless funds can be secured for the additional Bayley Scales of Infant Development III (Bayley N, Bayley Scales of Infant and Toddler Development, Third Edition. (Bayley-III), 2005) assessments. To assess accuracy of the cranial ultrasound diagnosis of intraventricular haemorrhage: (i) quality of the scans will be assessed using the British Society of Paediatric Radiology recommendations, and (ii) scan results will be confirmed by independent adjudication. Within and between adjudicator reliability will be assessed. In addition to the analyses planned to assess feasibility of the full trial based on data from the first year of recruitment, data on compliance and outcomes will be presented by allocated group for all women and babies recruited. TRIAL REGISTRATION: ISRCTN21456601, registered on 28 February 2013. PMID- 26370416 TI - Exome sequencing reveals mutation in GJA1 as a cause of keratoderma-hypotrichosis leukonychia totalis syndrome. PMID- 26370415 TI - Radix Scrophulariae extracts (harpagoside) suppresses hypoxia-induced microglial activation and neurotoxicity. AB - BACKGROUND: Hypoxia could lead to microglia activation and inflammatory mediators' overproduction. These inflammatory molecules could amplify the neuroinflammatory process and exacerbate neuronal injury. The aim of this study is to find out whether harpagoside could reduce hypoxia-induced microglia activation. METHODS: In this study, primary microglia cells harvested from neonatal ICR mice were activated by exposure to hypoxia (1 % O2 for 3 h). Harpagoside had been shown to be no cytotoxicity on microglia cells by MTT assay. The scavenger effect of harpagoside on hypoxia-enhanced microglial cells proliferation, associated inflammatory genes expression (COX-II, IL-1beta and IL 6 genes) and NO synthesis were also examined. RESULTS: Hypoxia enhances active proliferation of microglial cells, while harpagoside can scavenge this effect. We find that harpagoside could scavenge hypoxia-enhanced inflammatory genes expression (COX-2, IL-1beta and IL-6 genes) and NO synthesis of microglial cells. Under 3 h' hypoxic stimulation, the nuclear contents of p65 and hypoxia inducible factor-1alpha (HIF-1alpha) significantly increase, while the cytosol IkappaB alpha content decreases; these effects can be reversed by 1 h's pre-incubation of 10(-8) M harpagoside. Harpagoside could decrease IkappaB-alpha protein phosphorylation and inhibit p65 protein translocation from the cytosol to the nucleus, thus suppress NF-kappaB activation and reduce the HIF-1alpha generation. CONCLUSION: These results suggested that the anti-inflammatory mechanism of harpagoside might be associated with the NF-kappaB signaling pathway. Harpagoside protect against hypoxia-induced toxicity on microglial cells through HIF-alpha pathway. PMID- 26370417 TI - Altered glycolipid and glycerophospholipid signaling drive inflammatory cascades in adrenomyeloneuropathy. AB - X-linked adrenomyeloneuropathy (AMN) is an inherited neurometabolic disorder caused by malfunction of the ABCD1 gene, characterized by slowly progressing spastic paraplegia affecting corticospinal tracts, and adrenal insufficiency. AMN is the most common phenotypic manifestation of adrenoleukodystrophy (X-ALD). In some cases, an inflammatory cerebral demyelination occurs associated to poor prognosis in cerebral AMN (cAMN). Though ABCD1 codes for a peroxisomal transporter of very long-chain fatty acids, the molecular mechanisms that govern disease onset and progression, or its transformation to a cerebral, inflammatory demyelinating form, remain largely unknown. Here we used an integrated -omics approach to identify novel biomarkers and altered network dynamic characteristic of, and possibly driving, the disease. We combined an untargeted metabolome assay of plasma and peripheral blood mononuclear cells (PBMC) of AMN patients, which used liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry (LC-Q-TOF), with a functional genomics analysis of spinal cords of Abcd1(-) mouse. The results uncovered altered nodes in lipid-driven proinflammatory cascades, such as glycosphingolipid and glycerophospholipid synthesis, governed by the beta-1,4-galactosyltransferase (B4GALT6), the phospholipase 2gamma (PLA2G4C) and the choline/ethanolamine phosphotransferase (CEPT1) enzymes. Confirmatory investigations revealed a non-classic, inflammatory profile, consisting on the one hand of raised plasma levels of several eicosanoids derived from arachidonic acid through PLA2G4C activity, together with also the proinflammatory cytokines IL6, IL8, MCP-1 and tumor necrosis factor-alpha. In contrast, we detected a more protective, Th2-shifted response in PBMC. Thus, our findings illustrate a previously unreported connection between ABCD1 dysfunction, glyco- and glycerolipid-driven inflammatory signaling and a fine-tuned inflammatory response underlying a disease considered non-inflammatory. PMID- 26370418 TI - A novel conditional knock-in approach defines molecular and circuit effects of the DYT1 dystonia mutation. AB - DYT1 dystonia, the most common inherited form of primary dystonia, is a neurodevelopmental disease caused by a dominant mutation in TOR1A. This mutation ('DeltaE') removes a single glutamic acid from the encoded protein, torsinA. The effects of this mutation, at the molecular and circuit levels, and the reasons for its neurodevelopmental onset, remain incompletely understood. To uniquely address key questions of disease pathogenesis, we generated a conditional Tor1a knock-in allele that is converted from wild-type to DYT1 mutant ('induced' DeltaE: Tor1a(i-DeltaE)), following Cre recombination. We used this model to perform a gene dosage study exploring the effects of the DeltaE mutation at the molecular, neuropathological and organismal levels. These analyses demonstrated that DeltaE-torsinA is a hypomorphic allele and showed no evidence for any gain of-function toxic properties. The unique capabilities of this model also enabled us to test a circuit-level hypothesis of DYT1 dystonia, which predicts that expression of the DYT1 genotype (Tor1a(DeltaE/+)) selectively within hindbrain structures will produce an overtly dystonic animal. In contrast to this prediction, we find no effect of this anatomic-specific expression of the DYT1 genotype, a finding that has important implications for the interpretation of the human and mouse diffusion tensor-imaging studies upon which it is based. These studies advance understanding of the molecular effects of the DeltaE mutation, challenge current concepts of the circuit dysfunction that characterize the disease and establish a powerful tool that will be valuable for future studies of disease pathophysiology. PMID- 26370419 TI - The combinational therapy of trastuzumab and cetuximab inhibits tumor growth in a patient-derived tumor xenograft model of gastric cancer. AB - PURPOSE: Gastric cancer (GC) is one of the leading causes of cancer mortality worldwide. Although therapeutic strategies for GC have improved, the prognosis for advanced GC remains poor. Herein, the present study sought to design a personalized cancer therapy specific to a stage III GC patient. METHODS: The tumor was surgically removed and was used to establish a patient-derived tumor xenograft (PDTX) model utilizing nude mice. Various molecular-targeted anticancer treatments were tested in the study, including control (no treatment), bevacizumab, cetuximab, bevacizumab + cetuximab, trastuzumab, and trastuzumab + cetuximab. RESULTS: Trastuzumab + cetuximab treatment exhibited the best antitumor growth effect, followed by trastuzumab, bevacizumab + cetuximab, cetuximab, and bevacizumab. Similarly, trastuzumab + cetuximab was also the most effective treatment at inducing apoptosis and cell cycle arrest in primary cultures of the patient's gastric cancer cells. Among all treatments tested in the study, trastuzumab + cetuximab showed the most profound effect in reducing the protein expression of proliferation and metastatic markers (VEGF, MMP-7, EGFT, Ki-67 and, PCNA) in tumors obtained from PDTX models, which may be the mechanism underlying the profound antitumor growth effect exerted by trastuzumab + cetuximab. CONCLUSIONS: The data indicate that trastuzumab + cetuximab combinational therapy should be the most effective antitumor growth therapy for the GC patient whom we took the cancer cells from. PMID- 26370420 TI - The position and current status of radiation therapy after primary systemic therapy in breast cancer: a national survey-based expert consensus statement. AB - BACKGROUND: Primary systemic therapy (PST) is changing the role of radiation therapy (RT) in breast cancer. Without randomized studies, the optimal indications for RT after PST and surgery are not clear. The present study provides consensus-based recommendations to clarify the role of RT. METHODS: Radiation oncologists (n = 82; 77 % response rate) in Spain were surveyed to determine their recommendations for locoregional RT following PST and surgery. RESULTS: Most (98 %) specialists support whole breast irradiation after breast conserving surgery (BCS), regardless of pathologic response to PST. In T1-T2 and T3-T4 tumours with sentinel node biopsy (SNB) prior to PST, 91 and 56 % of respondents, respectively, recommend irradiating the supraclavicular (level IV) and axillary level III nodes when nodal involvement is detected (9 and 44 % of respondents recommend irradiating these areas by independent of nodal status). If SNB is not available, 57 and 30 % of specialists agreed that the aforementioned nodal regions should be irradiated (33 and 65 % of respondents recommend irradiating these areas by independent of nodal status). Between 58 and 76 % of specialists agreed that nodal levels I and II should be irradiated in cases of insufficient lymphadenectomy or when >75 % of the resected nodes are involved. CONCLUSION: Agreement is strong regarding the indications for local RT after PST and surgery, but less so for nodal irradiation. All patients who undergo BCS should receive RT, even with complete pathologic response. After mastectomy, RT is recommended in all node-positive stage III cases. Prospective studies will clarify indications for RT in this patient population. PMID- 26370421 TI - Overexpression of forkhead box protein M1 (FOXM1) plays a critical role in colorectal cancer. AB - BACKGROUND: The forkhead box M1 (FOXM1), an important regulator of cell differentiation and proliferation, is overexpressed in a number of aggressive human carcinomas. However, the clinical significance of FOXM1 signaling in human colorectal cancer (CRC) pathogenesis remains unknown. The aim of this study was to evaluate the role of FOXM1 in CRC tumorigenesis. METHODS: We investigated FOXM1 expression in 103 cases of primary CRC and matched normal tissue specimens and explored the underlying mechanisms of altered FOXM1 expression and the impact of this altered expression on CRC proliferation and metastasis using in vitro models of CRC. RESULTS: The results showed that high expression of FOXM1 staining was 85.44% (88/103) in 103 cases of CRC and 20.39% (21/103) in 103 cases of adjacent non-cancerous tissue samples; the difference of FOXM1 expression between two groups was statistically significant (P < 0.001). Silencing of FOXM1 inhibited the proliferation of CRC cells, and the invasion and migration of CRC cells were distinctly suppressed. Furthermore, FOXM1 knockdown led to substantial reductions in VEGF-A levels in CRC cell lines. CONCLUSIONS: Our data suggest that the pathogenesis of CRC maybe mediated by FOXM1, and FOXM1 could represent selective targets for the molecularly targeted treatments of CRC. PMID- 26370422 TI - Concurrent chemo-radiotherapy in elderly patients: tolerance and compliance in a series of 137 patients. AB - INTRODUCTION: Aggressive cancer treatment is a challenge in elderly patients. The present study aims to assess tolerance in terms of acute toxicity and compliance of concurrent chemo-radiotherapy (cCRT) in a series of patients aged >=70 years. MATERIALS AND METHODS: Clinical records of patients aged >=70 years who underwent cCRT between January 2005 and December 2013 were reviewed. Concurrent CRT had curative intent in 134 patients (97.8 %) and palliative intent in 3 patients (2.2 %). Chemotherapy (CT) drugs and schedule were selected according to tumor histology. Radiotherapy median dose was 45.0 Gy (range 11-70 Gy) for curative purposes and 54 Gy (range 40-56 Gy) for palliative purposes. Incidence of acute toxicity and compliance to cCRT were analyzed and correlated with age, Karnofsky Performance Status (KPS), and Charlson Comorbidity Index (CCI). RESULTS: Overall, 137 patients, 82 males (60 %) and 55 females (40 %), median age 74 years (range 70-90 years) were analyzed. Concurrent CRT schedule was completed by 132 patients (96.4 %). Thirty-one of these patients (23.5 %) temporarily interrupted treatment. Hematological toxicity with grade >=1 was observed in 25 patients (18.2 %), gastrointestinal toxicity in 55 (40.1 %), and genitourinary in 13 (9.5 %). Mucositis with grade >=1 was recorded in 19 patients (13.9 %). No statistical significant correlation between KPS, CCI, and toxicity was found. A correlation trend between mucositis and patient age (p = 0.05) was observed. CONCLUSION: Concurrent CRT for elderly was feasible and quite well tolerated. Great attention in prescribing CT dose should be paid to limit acute toxicity. PMID- 26370424 TI - Paragonimiasis Due to the Consumption of Wild Boar Meat in Japan: Contamination Levels of Lung Fluke Larvae in Muscle Samples of Wild Boars Caught in Kagoshima Prefecture. PMID- 26370425 TI - Possible Rickettsia massiliae Infection in Greece: an Imported Case. AB - Tick-borne rickettsioses are endemic in Greece; however, until recently, only Rickettsia typhi and R. conorii were tested routinely in human samples arriving at the National Reference Center. During the last few years, the identification of different rickettsia species in ticks led to the introduction of other spotted fever group rickettsiae in routine analysis. Under the new scheme, R. massiliae is now tested routinely in human samples; herein, we describe a human case of this infection. PMID- 26370423 TI - Non-coding RNAs deregulation in oral squamous cell carcinoma: advances and challenges. AB - Oral squamous cell carcinoma (OSCC) is a common cause of cancer death. Despite decades of improvements in exploring new treatments and considerable advance in multimodality treatment, satisfactory curative rates have not yet been reached. The difficulty of early diagnosis and the high prevalence of metastasis associated with OSCC contribute to its dismal prognosis. In the last few decades the emerging data from both tumor biology and clinical trials led to growing interest in the research for predictive biomarkers. Non-coding RNAs (ncRNAs) are promising biomarkers. Among numerous kinds of ncRNAs, short ncRNAs, such as microRNAs (miRNAs), have been extensively investigated with regard to their biogenesis, function, and importance in carcinogenesis. In contrast to miRNAs, long non-coding RNAs (lncRNAs) are much less known concerning their functions in human cancers especially in OSCC. The present review highlighted the roles of miRNAs and newly discovered lncRNAs in oral tumorigenesis, metastasis, and their clinical implication. PMID- 26370426 TI - Proteomic Profiling of a Respiratory Syncytial Virus-Infected Rat Pneumonia Model. AB - Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract disease in pediatric patients. Our goal was to obtain a detailed understanding of the molecular pathogenesis of RSV infections by studying the protein expression profiles in rats with pneumonia. First, we successfully established a pneumonia rat model by intranasally injecting RSV. The differentially expressed proteins in lung tissues of RSV-infected rats compared with those of the controls were analyzed by using 2-dimensional fluorescence difference gel electrophoresis and MALDI-TOF/TOF MS. In total. 41 differentially expressed protein spots representing 20 unique proteins were successfully identified. Classification analysis showed that most of these proteins are implicated in metabolic processes, cellular processes, cellular component organization or biogenesis, and immune system processes. The significantly elevated expressions levels of 4 proteins namely, T-kininogen 1, T-kininogen 2, haptoglobin, and hemopexin, which might serve as the potential biomarkers of RSV-infected pneumonia, were further validated in RSV-infected rats using western blot and immunohistochemistry. These results provide new insights into the pathogenesis of RSV infection-induced pneumonia and provide important future directions for functional studies and therapeutic design. PMID- 26370427 TI - Rotavirus Infection in Children with Diarrhea at Korle-Bu Teaching Hospital, Ghana. AB - Human rotavirus infection was studied over a 13-month period (January 2004 to January 2005) in children <5 years of age admitted with severe diarrhea at the Korle-Bu Teaching Hospital in Accra, Ghana. During this period, 206 hospitalizations for diarrhea were recorded, with 34.0% (70/206) being positive for rotavirus infection. Infection occurred throughout the year, with peak rotavirus infection occurring during the month of March. Hospitalization associated with rotaviruses was most common in the 6-8 month age group. The case fatality rate of rotavirus infection was 2.9% (2/70) and occurred in children <12 months of age. Four rotavirus VP7 genotypes (G1, G2, G3, and G9) were detected. The predominant genotypes were G2 (22.9%), G1 (17.1%), G9 (17.1%) and G3 (12.9%). Mixed G types were also detected. The predominant VP4 genotypes (P types) were P[6] (38.6%), P[8] (21.4%), P[4] (4.3%) and P[9] (1.4%). The predominant rotavirus strains infecting children in Accra were G9P[6] (10.0%) and G1P[8] (8.6%). Strains with unusual genotypes such as G2P[8] and G(2/3)P[6] were also detected. PMID- 26370428 TI - Using an Autoregressive Integrated Moving Average Model to Predict the Incidence of Hemorrhagic Fever with Renal Syndrome in Zibo, China, 2004-2014. AB - Hemorrhagic fever with renal syndrome (HFRS) is highly endemic in mainland China, where human cases account for 90% of the total global cases. Zibo City is one of the most seriously affected areas in Shandong Province, China. Therefore, there is an urgent need for monitoring and predicting HFRS incidence in Zibo to make the control of HFRS more effective. In this study, we constructed an autoregressive integrated moving average (ARIMA) model for monthly HFRS incidence in Zibo from 2004 to 2013. The ARIMA (3,1,1) * (2,1,1)12 model is reliable with a high validity, which can be used to predict the next year's HFRS incidence in Zibo. The forecast results suggest that the HFRS incidence in Zibo will experience a slight growth in the next year. PMID- 26370429 TI - A Case of Human Infection by Rickettsia slovaca in Greece. AB - Although tick-borne rickettsiosis is endemic in Greece, until recently, human samples arriving at the National Reference Centre under suspicion of rickettsial infection were routinely tested only for Rickettsia typhi and R. conorii. However, identification of additional rickettsia species in ticks prompted revision of the protocol in 2010. Until that year, all human samples received by the laboratory were tested for antibodies against R. conorii and R. typhi only. Now, tests for R. slovaca, R. felis, and R. mongolotimonae are all included in routine analysis. The current description of a human R. slovaca case is possible as a result of these changes in routine testing. PMID- 26370430 TI - Prevalence of Providencia Strains among Patients with Diarrhea and in Retail Meats in Thailand. AB - In the present study, we examined the prevalence of Providencia spp. in retail meats and in stool samples from diarrheal patients in Thailand. Providencia specific (Psp)-PCR amplification was positive for 58% (15/26) of the chicken, 64% (16/25) of the pork, and 68% (17/25) of the beef samples. Subsequently, Providencia strains were isolated from 65% (17/26) of the chicken, 68% (17/25) of the pork, and 72% (18/25) of the beef samples. Although P. alcalifaciens (40-58%) was the most prevalent Providencia strain, P. rettgeri, P. stuartii, and P. rustigianii were also isolated. Of the patient stool samples tested, 7.5% (16/214) had Psp-PCR products, of which 4 were P. alcalifaciens (1.9%), 4 were P. rettgeri (1.9%), and 1 was P. stuartii (0.5%). In conclusion, retail meats were substantially contaminated with Providencia, especially P. alcalifaciens. Therefore, retail meats are possibly the source of Providencia infections in humans. PMID- 26370431 TI - High Prevalence of G12 Human Rotaviruses in Children with Gastroenteritis in Myanmar. AB - Human rotavirus samples from 54 children with acute gastroenteritis in Myanmar in 2011 were subjected to reverse transcription-PCR to determine their G and P types. On G typing, G2 (24/54; 44.4%) was found to be the most prevalent, followed by G12 (17/54; 31.5%) and G1 (1/54; 1.9%). Mixed cases with G2 and G12 were found in 12 of the 54 (22.2%) samples. On P typing, P[4] was found to be the most predominant (29/54; 53.7%), followed by P[8] (17/54; 31.5%) and P[6] (4/54; 7.4%). Mixed cases with P[4] and P[8] were detected in 4 of 54 (7.4%) samples. Thus, occurrence of G2 and unusual G12 in high proportions was characteristic of human rotaviruses in Myanmar in this study setting. PMID- 26370432 TI - Age Group-Based Monitoring of the Progress in Measles and Rubella Elimination: Search for a Population Size/Density-Independent Parameter. PMID- 26370433 TI - Increase in Primary and Secondary Syphilis Notifications in Men in Tokyo, 2007 2013. AB - The number of notified syphilis cases in Tokyo has more than doubled in recent years. The number of reported primary and secondary syphilis cases increased from 108 cases (0.8 per 100,000 population) in 2007 to 245 cases in 2013 (1.9 per 100,000 population). During this period, the majority of cases was male (905/1,024), and the recent increase among primary and secondary syphilis cases was attributed to the increase among males (90/108 [83%] cases in 2007 to 218/245 [89%] cases in 2013); men aged 20-49 years contributed most to the increase, with those aged 30-34 years having the highest notification rate in 2013. Male-to-male transmission was the primary route of infection reported, and men who have sex with men (MSM) accounted for nearly 80% of male cases in 2013. Syphilis appears to be reemerging in Tokyo, and reducing the risk of acquiring syphilis among MSM aged 20-49 years should be a public health priority in Tokyo. PMID- 26370434 TI - Fabrication and characterization of micro-porous cellulose filters for indoor air quality control. AB - Micro-porous cellulose filters were fabricated from paper mulberry pulp, which has been used for thousands of years with Korean history. 'Han-ji' is the name of a traditional paper used widely in Korea in construction, textile, craftworks and many household items but before now it has not been used for filtration purpose. Seeking for the utilization of this abundant natural material, this study aims to develop a fabrication process for the traditional paper to be used as a filter for dust filtration, and evaluate the performance by lab-scale experiments. To create pores in the paper, cellulose pulp was pretreated using several methods such as TEMPO oxidation and enzyme hydrolysis, or freeze dried with an alcoholic freezing medium, t-butyl alcohol, instead of water. The filters were characterized and their dust removal performance was tested at a lab scale while also monitoring pressure loss. Chemical oxidation and enzymatic pretreatment were helpful in fabricating a homogeneous filter but would not remove fine-dust particles because of its loose, enlarged pores. The best removal efficiency was observed with filters that were not pretreated but in which water had been exchanged with t-butyl alcohol before freeze-drying. The filter attained a dust removal efficiency higher than 99% over the entire experimental period, with a pressure loss of less than 230 Pa, at a 6.67 (cm3/s)/cm2 air-to-cloth ratio. PMID- 26370435 TI - Sex inequalities in cardiovascular health: a cross-sectional study. AB - BACKGROUND: The aim of this study was to determine sex differences in the prevalence of cardiovascular health (CVH) metrics according to the CVH status. METHODS: The cross-sectional, population-based study involved 2250 women and 1920 men aged >=18 years that participated in the 2010 National Health Survey in the Republic of Srpska, Bosnia and Herzegovina. Prevalence of CVH behaviours (smoking, body mass index, physical activity, diet), CVH factors (cholesterol, fasting blood glucose and blood pressure, plus smoking) and ideal CVH were estimated according to the American Heart Association criteria for ideal, intermediate and poor levels. Association between sex and ideal CVH categories was analyzed with multivariable logistic regression analysis across three age stratums. RESULTS: A higher prevalence of ideal CVH metrics was seen in women for smoking status, body mass index, healthy diet score and blood pressure, and in men for physical activity and total cholesterol. Women from all age groups had better CVH behaviours (odds ratio [OR] = 1.40 for the youngest; OR = 2.05 for middle-aged; and OR = 2.03 for older-aged women), while only women from the youngest age group had better CVH factors (OR = 5.09). In line with this, ideal overall CVH prevailed in younger and middle-aged women in comparison to men of the same ages (OR = 3.01 and OR = 2.25, respectively), while disappeared in older ones. CONCLUSIONS: Significant differences in the prevalence of CVH metrics between men and women in the Republic of Srpska should be considered in cardiovascular disease prevention. PMID- 26370436 TI - Framework convention on tobacco control: 10 years of the pioneering global health instrument. PMID- 26370437 TI - Colorectal cancer screening participation: a systematic review. AB - BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers in men and women. CRC screening programmes have been implemented in various countries. However, the participation rate remains disappointingly low. For a screening method to be beneficial, high participation rates are essential. Therefore, understanding the factors that are associated with CRC screening and follow-up adherence is necessary. In this systematic review, factors studied in literature were identified that are associated with CRC screening adherence. METHODS: A systematic search in PUBMED, EMBASE and COCHRANE was performed to identify barriers and facilitators for CRC screening adherence. Study characteristics were summarized and analysed. RESULTS: Seventy-seven papers met the inclusion criteria to be applicable for review. Female gender, younger participants, low level of education, lower income, ethnic minorities and not having a spouse were the most frequently reported barriers. Health provider characteristics, such as health insurance and a usual source of care were also frequently reported barriers in CRC screening adherence. Disparities were found in weight, employment status and self-perceived health status. CONCLUSION: Barriers and facilitators of CRC screening participation are frequently reported. Understanding these factors is the first step to possibly modify specific factors to increase CRC screening participation rate. PMID- 26370438 TI - The effect of competition on the relationship between the introduction of the DRG system and quality of care in Korea. AB - BACKGROUND: The diagnosis-related group-based prospective payment programme was introduced in Korea in 1997 as a pilot programme to control health spending. In July 2013, the programme was implemented throughout the nation. The aim of our study is to evaluate the relationship between quality of care and market competition following the introduction of the new payment system in Korea. METHODS: We conduct an observational analysis using National Health Insurance claim data from 2011 to 2014. We analyse data on readmission within 30 days, length of stay, and number of outpatient visits for 1742 hospitals and 821 912 cases. We use a generalized estimating equation model to evaluate readmission within 30 days and number of outpatient visits and a multi-level regression model to assess length of stay. RESULTS: Total readmission within 30 days is 10 727 (1.3%). High competition areas present a lower risk of readmission [odds ratio (OR): 0.95, P: 0.0277], a longer length of stay (1%, P < 0.0001), and an increased number of outpatient visits (Relative Risk: 1.11, P: 0.0011) as compared with moderate competition areas. Risk of readmission is higher in low competition areas as compared with moderate competition areas (OR: 1.21, P < 0.0001). CONCLUSION: The effects of the introduction of the new payment system differed by degree of market competition. Thus, evaluation about the effect of new payment system on hospital performance should be measured in combination with the degree of hospital market structure. PMID- 26370439 TI - Educational inequality as a predictor of rising back pain prevalence in Austria sex differences. AB - BACKGROUND: Back pain (BP) represents a widespread public health problem in Europe. The morbidity depends on several indicators, which must be investigated to discover risk groups. The examination of trends in socioeconomic developments should ensure a better understanding of the complex link between socioeconomic status and BP. Therefore, the role of social inequalities for BP has been investigated among Austrian subpopulations over a 24-year period. METHODS: Self reported data from nationally representative health surveys (1983-2007) were analyzed and adjusted for self-report bias (N=121 486). Absolute changes (ACs) and aetiologic fractions (AF) were calculated to measure trends. To quantify the extent of social inequality, the relative index of inequality was computed based on educational levels. RESULTS: The prevalence of BP nearly doubled between 1983 and 2007. When investigating educational groups, subjects with low educational level were most prevalent. Obese persons generally showed higher rates of BP than non-obese subjects. Continuously rising trends across the different educational groups were more evident in men. The AC was highest in obese men with high education (+32.9%). Education-related inequalities for BP were more evident in men than women. CONCLUSION: Educational level is an important social indicator for BP. A gradient for low to high educational level in the trends of BP prevalence was clearly identified and stable only among men. We presume that the association 'education' and 'physical workload leading to BP' is more relevant for men than for women. The implementation of effective approaches to BP, in combination with target group-specific interventions focusing on educational status, is recommended. PMID- 26370440 TI - Cost-effectiveness of screening for lung cancer with low-dose computed tomography: a systematic literature review. AB - BACKGROUND: On 31 December 2013, the US Preventive Services Task Force rated low dose computed tomography (LDCT) for lung cancer screening as level 'B' recommendation. Yet, lung cancer screening implementation remains controversial, particularly when considering its cost-effectiveness. The aim of this work is to investigate the cost-effectiveness of LDCT screening program for lung cancer by performing a systematic literature review. METHODS: We reviewed the published economic evaluations of LDCT in lung cancer screening. MEDLINE, ISI Web of Science and Cochrane databases were searched for literature retrieval up to 31 March 2015. Inclusion criteria included: studies reporting an original full economic evaluation; reports presenting the outcomes as Quality-Adjusted Life Years (QALYs) gained or as Life Years Gained. RESULTS: Nine economic evaluations met the inclusion criteria. All the cost-effectiveness analyses included high risk populations for lung cancer and compared the use of annual LDCT screening with no screening. Seven studies reported an incremental cost-effectiveness ratio below the threshold of US$ 100 000 per QALY gained. CONCLUSIONS: Cost effectiveness of LDCT screening for lung cancer is an highly debatable issue. Currently available economic evaluations suggest the cost-effectiveness of LDCT for lung cancer screening compared with no screening and indicate that the implementation of LDCT should be considered when planning a national lung cancer screening program. Additional economic evaluations, especially from a societal perspective and in an EU-setting, are needed. PMID- 26370441 TI - Significance of NF-kappaB activation in immortalization of nasopharyngeal epithelial cells. AB - NF-kappaB is a key regulator of inflammatory response and is frequently activated in human cancer including the undifferentiated nasopharyngeal carcinoma (NPC), which is common in Southern China including Hong Kong. Activation of NF-kappaB is common in NPC and may contribute to NPC development. The role of NF-kappaB activation in immortalization of nasopharyngeal epithelial (NPE) cells, which may represent an early event in NPC pathogenesis, is unknown. Examination of NF kappaB activation in immortalization of NPE cells is of particular interest as the site of NPC is often heavily infiltrated with inflammatory cellular components. We found that constitutive activation of NF-kappaB signaling is a common phenotype in telomerase-immortalized NPE cell lines. Our results suggest that NF-kappaB activation promotes the growth of telomerase-immortalized NPE cells, and suppression of NF-kappaB activity inhibits their proliferation. Furthermore, we observed upregulation of c-Myc, IL-6 and Bmi-1 in our immortalized NPE cells. Inhibition of NF-kappaB downregulated expression of c Myc, IL-6 and Bmi-1, suggesting that they are downstream events of NF-kappaB activation in immortalized NPE cells. We further delineated that EGFR/MEK/ERK/IKK/mTORC1 is the key upstream pathway of NF-kappaB activation in immortalized NPE cells. Elucidation of events underlying immortalization of NPE cells may provide insights into early events in pathogenesis of NPC. The identification of NF-kappaB activation and elucidation of its activation mechanism in immortalized NPE cells may reveal novel therapeutic targets for treatment and prevention of NPC. PMID- 26370442 TI - Intracellular detection of Cu(2+) and S(2-) ions through a quinazoline functionalized benzimidazole-based new fluorogenic differential chemosensor. AB - A new quinazoline functionalized benzimidazole-based fluorogenic chemosensor H3L is synthesized and fully characterized by conventional techniques including single crystal X-ray analysis. It acts as a highly selective colorimetric and fluorescence sensor for Cu(2+) ions in DMF/0.02 M HEPES (1 : 1, v/v, pH = 7.4) medium. Reaction of H3L with CuCl2 forms a mononuclear copper(ii) [Cu(Cl)(H2L)(H2O)] (H2L-Cu(2+)) complex which is characterized by conventional techniques and quantum chemical calculations. Electronic absorption and fluorescence titration studies of H3L with different metal cations show a distinctive recognition only towards Cu(2+) ions even in the presence of other commonly coexisting ions such as Li(+), Na(+), K(+), Mg(2+), Ca(2+), Fe(2+), Fe(3+), Mn(2+), Co(2+), Ni(2+), Zn(2+), Cd(2+) and Hg(2+). Moreover, H2L-Cu(2+) acts as a metal based highly selective and sensitive chemosensor for S(2-) ions even in the presence of other commonly coexisting anions such as F(-), Cl(-), Br( ), I(-), SO4(2-), SCN(-), AcO(-), H2PO4(-), PO4(3-), NO3(-), ClO4(-), NO2(-), HSO4(-), HSO4(2-), S2O3(2-), S2O8(2-), CN(-), CO3(2-) and HCO3(-) in DMF/0.02 M HEPES (1 : 1, v/v, pH = 7.4) medium. Quantification analysis indicates that these receptors, H3L and H2L-Cu(2+), can detect the presence of Cu(2+) and S(2-) ions at very low concentrations of 1.6 * 10(-9) M and 5.2 * 10(-6) M, respectively. The propensity of H3L as a bio-imaging fluorescent probe for detection of Cu(2+) ions and sequential detection of S(2-) ions by H2L-Cu(2+) in Dalton lymphoma (DL) cancer cells is also shown. PMID- 26370443 TI - The MamaMiso study of self-administered misoprostol to prevent bleeding after childbirth in rural Uganda: a community-based, placebo-controlled randomised trial. AB - BACKGROUND: 600 mcg of oral misoprostol reduces the incidence of postpartum haemorrhage (PPH), but in previous research this medication has been administered by health workers. It is unclear whether it is also safe and effective when self administered by women. METHODS: This placebo-controlled, double-blind randomised trial enrolled consenting women of at least 34 weeks gestation, recruited over a 2-month period in Mbale District, Eastern Uganda. Participants had their haemoglobin measured antenatally and were given either 600 mcg misoprostol or placebo to take home and use immediately after birth in the event of delivery at home. The primary clinical outcome was the incidence of fall in haemoglobin of over 20% in home births followed-up within 5 days. RESULTS: 748 women were randomised to either misoprostol (374) or placebo (374). Of those enrolled, 57% delivered at a health facility and 43% delivered at home. 82% of all medicine packs were retrieved at postnatal follow-up and 97% of women delivering at home reported self-administration of the medicine. Two women in the misoprostol group took the study medication antenatally without adverse effects. There was no significant difference between the study groups in the drop of maternal haemoglobin by >20% (misoprostol 9.4% vs placebo 7.5%, risk ratio 1.11, 95% confidence interval 0.717 to 1.719). There was significantly more fever and shivering in the misoprostol group, but women found the medication highly acceptable. CONCLUSIONS: This study has shown that antenatally distributed, self administered misoprostol can be appropriately taken by study participants. The rarity of the primary outcome means that a very large sample size would be required to demonstrate clinical effectiveness. TRIAL REGISTRATION: This study was registered with the ISRCTN Register (ISRCTN70408620). PMID- 26370444 TI - Efficiency of a phone coaching program on adherence to continuous positive airway pressure in sleep apnea hypopnea syndrome: a randomized trial. AB - BACKGROUND: Continuous Positive Airway Pressure (CPAP) remains the reference treatment for moderate to severe forms of the Sleep Apnea/Hypopnea Syndrome (SAHS). Compliance to the treatment appears to be a key factor to improving health status of these patients. METHODS: We conducted a multicenter, prospective, randomized, controlled, parallel group trial of standard support completed or not within 3 months of coaching sessions for newly diagnosed SAHS patients starting CPAP therapy. This study has been recorded by AFSSAPS with the RCB number: 2009-A01127-50 and received favourably by the Human Studies Committee in France. The coaching session consisted of 5 sessions of telephone-based counselling by competent staff. The primary outcome was the proportion of patients using CPAP more than 3 h per night for 4 months; the secondary outcome was mean hours of CPAP usage in the 2 groups. RESULTS: Three hundred and seventy nine patients fulfilled the inclusion criteria and were randomized. The percentage of patients using CPAP more than 3 h per night for 4 months was 65 % for the standard support group and 75 % for the coached group. This difference reached a statistical significance (chi2 = 3.97). The mean CPAP usage was increased in the coached group versus standard group. A difference of 26 min was observed (4 h34+/-2 h17 and 4 h08+/-2 h25 respectively, p = 0.04). CONCLUSION: This study shows that SAHS patients who benefit from phone coaching are statistically more compliant to CPAP than a standard support group is. A simple phone coaching procedure based on knowledge of the disease and reinforcement messages about treatment benefits helps to improve CPAP adherence in SAHS patients. TRIAL REGISTRATION: NCT02435355. PMID- 26370445 TI - Increased Heart Rate Is Associated With Higher Mortality in Patients With Atrial Fibrillation (AF): Results From the Outcomes Registry for Better Informed Treatment of AF (ORBIT-AF). AB - BACKGROUND: Most patients with atrial fibrillation (AF) require rate control; however, the optimal target heart rate remains under debate. We aimed to assess rate control and subsequent outcomes among patients with permanent AF. METHODS AND RESULTS: We studied 2812 US outpatients with permanent AF in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation. Resting heart rate was measured longitudinally and used as a time-dependent covariate in multivariable Cox models of all-cause and cause-specific mortality during a median follow-up of 24 months. At baseline, 7.4% (n=207) had resting heart rate <60 beats per minute (bpm), 62% (n=1755) 60 to 79 bpm, 29% (n=817) 80 to 109 bpm, and 1.2% (n=33) >=110 bpm. Groups did not differ by age, previous cerebrovascular disease, heart failure status, CHA2DS2-VASc scores, renal function, or left ventricular function. There were significant differences in race (P=0.001), sinus node dysfunction (P=0.004), and treatment with calcium-channel blockers (P=0.006) and anticoagulation (P=0.009). In analyses of continuous heart rates, lower heart rate <=65 bpm was associated with higher all-cause mortality (adjusted hazard ratio [HR], 1.15 per 5-bpm decrease; 95% CI, 1.01 to 1.32; P=0.04). Similarly, increasing heart rate >65 bpm was associated with higher all-cause mortality (adjusted HR, 1.10 per 5-bpm increase; 95% CI, 1.05 to 1.15; P<0.0001). This relationship was consistent across endpoints and in a broader sensitivity analysis of permanent and nonpermanent AF patients. CONCLUSIONS: Among patients with permanent AF, there is a J-shaped relationship between heart rate and mortality. These data support current guideline recommendations, and clinical trials are warranted to determine optimal rate control. CLINICAL TRIAL REGISTRATION: URL: http://clinicaltrials.gov/. Unique identifier: NCT01165710. PMID- 26370446 TI - Persistently Altered Brain Mitochondrial Bioenergetics After Apparently Successful Resuscitation From Cardiac Arrest. AB - BACKGROUND: Although advances in cardiopulmonary resuscitation have improved survival from cardiac arrest (CA), neurologic injury persists and impaired mitochondrial bioenergetics may be critical for targeted neuroresuscitation. The authors sought to determine if excellent cardiopulmonary resuscitation and postresuscitation care and good traditional survival rates result in persistently disordered cerebral mitochondrial bioenergetics in a porcine pediatric model of asphyxia-associated ventricular fibrillation CA. METHODS AND RESULTS: After 7 minutes of asphyxia, followed by ventricular fibrillation, 5 female 1-month-old swine (4 sham) received blood pressure-targeted care: titration of compression depth to systolic blood pressure of 90 mm Hg and vasopressor administration to a coronary perfusion pressure >20 mm Hg. All animals received protocol-based vasopressor support after return of spontaneous circulation for 4 hours before they were killed. The primary outcome was integrated mitochondrial electron transport system (ETS) function. CA animals displayed significantly decreased maximal, coupled oxidative phosphorylating respiration (OXPHOSCI + CII) in cortex (P<0.02) and hippocampus (P<0.02), as well as decreased phosphorylation and coupling efficiency (cortex, P<0.05; hippocampus, P<0.05). Complex I- and complex II-driven respiration were both significantly decreased after CA (cortex: OXPHOSCI P<0.01, ETSCII P<0.05; hippocampus: OXPHOSCI P<0.03, ETSCII P<0.01). In the hippocampus, there was a significant decrease in maximal uncoupled, nonphosphorylating respiration (ETSCI + CII), as well as a 30% reduction in citrate synthase activity (P<0.04). CONCLUSIONS: Mitochondria in both the cortex and hippocampus displayed significant alterations in respiratory function after CA despite excellent cardiopulmonary resuscitation and postresuscitation care in asphyxia-associated ventricular fibrillation CA. Analysis of integrated ETS function identifies mitochondrial bioenergetic failure as a target for goal directed neuroresuscitation after CA. IACUC Protocol: IAC 13-001023. PMID- 26370447 TI - Adequate Selection of a Therapeutic Site Enables Efficient Development of Collateral Vessels in Angiogenic Treatment With Bone Marrow Mononuclear Cells. AB - BACKGROUND: Induction of angiogenic mechanisms to promote development of collateral vessels is considered promising for the treatment of peripheral arterial diseases. Collateral vessels generally develop from preexisting arteriolar connections, bypassing the diseased artery. We speculated that induction of angiogenic mechanisms should be directed to such arteriolar connections to achieve efficient collateral development. The aim of this study was to verify this hypothesis using autologous transplantation of bone marrow mononuclear cells in the rabbit model of chronic limb ischemia. METHODS AND RESULTS: The left femoral artery was excised to induce limb ischemia in male rabbits. In this model, arteriolar connections in the left coccygeofemoral muscle tend to develop into collateral vessels, although this transformation is insufficient to alleviate the limb ischemia. In contrast, arteriolar connections in the closely located adductor muscle do not readily develop into collateral vessels. At 21 days after ischemia initiation, a sufficient number of automononuclear cells were selectively injected in the left coccygeofemoral muscle (coccygeo group) or left adductor muscle (adductor group). Evaluation of calf blood pressure ratios, blood flow in the left internal iliac artery, and angiographic scores at day 28 after injection revealed that collateral development and improvement of limb ischemia were significantly more efficient in the coccygeo group than in the adductor group. Morphometric analysis of the coccygeofemoral muscle at day 14 showed similar results. CONCLUSIONS: Specific delivery of mononuclear cells to the coccygeofemoral but not the adductor muscle effectively improves collateral circulation in the rabbit model of limb ischemia and suggests that adequate site selection can facilitate therapeutic angiogenesis. PMID- 26370449 TI - Lighting and Nurses at Medical-Surgical Units: Impact of Lighting Conditions on Nurses' Performance and Satisfaction. AB - OBJECTIVE: This study investigates the perception of nurses about their lighting environment at medical-surgical hospital units in order to understand areas of improvement for lighting at these units. BACKGROUND: The bulk of the research about nurses and lighting is focused on nighttime nursing, exploring the disruptions of nurses' circadian rhythm and maintaining alertness. The understanding of nurses' perception about lighting and its impact on nurses' task performance and patient examination remains imprecise. METHODS: This study used an online survey to ask a set of questions about lighting in medical-surgical units at five key locations including centralized nurse stations, decentralized nurse stations (DCNS), patient bedsides, patient bathrooms, and corridors from 393 survey participants. It then explored the survey findings in more depth through conducting focus groups with eight volunteer nurses. RESULTS: Lighting conditions at patient besides and DCNSs were significantly less desirable for nurses compared to other locations. A significant relationship between nurses' access to lighting controls (switches and dimmers) and satisfaction about the lighting environment was found. No significant relationship was observed between the individual characteristics of nurses (such as age, years of experience, etc.) and findings of this study. CONCLUSIONS: Thoughtful design of the lighting environment can improve nurses' satisfaction and perception about their working environment. PMID- 26370448 TI - High-Density Lipoprotein Subclasses and Noncardiovascular, Noncancer Chronic Inflammatory-Related Events Versus Cardiovascular Events: The Multi-Ethnic Study of Atherosclerosis. AB - BACKGROUND: High-density lipoprotein (HDL) particles have properties beyond reverse cholesterol transport. We hypothesized that their protection extends to inflammation-related disease. The predictive value of HDL particle subclasses and inflammatory markers was studied for noncardiovascular, noncancer chronic inflammation-related death and hospitalization, and for incident cardiovascular disease (CVD). METHODS AND RESULTS: A multiethnic, multicenter, prospective observational study was conducted in 6475 men and women (aged 45 to 84 years) free of known CVD at baseline with median follow-up of 10.1 years. Fasting venous samples were analyzed for baseline lipid profile and lipoprotein particles. We focused on the HDL family of variables (small-, medium-, and large-diameter HDL particles and HDL cholesterol). Analyses identified the sum of small- plus medium diameter HDL particles as important. Small- plus medium-diameter HDL particles were inversely associated with diagnostic code-based noncardiovascular, noncancer chronic inflammation-related death and hospitalization (n=1054) independent of covariates: relative risk per SD 0.85 (95% CI: 0.79 to 0.91, P<0.0001). Small- plus medium-diameter HDL particles were also associated with adjudicated fatal and nonfatal coronary heart disease events (n=423): relative risk per SD 0.88 (95% CI 0.77 to 0.98, P=0.02). CONCLUSIONS: Small- plus medium-diameter HDL particles are an independent predictor for noncardiovascular, noncancer chronic inflammation-related death and hospitalization and for coronary heart disease events in subjects initially free of overt CVD. These findings support the hypothesis that smaller HDL particles of diameter <9.4 nm have anti-inflammatory properties in the general population. PMID- 26370450 TI - Weighing the surface charge of an ionic liquid. AB - Electrochemical quartz crystal microbalance has been used to measure changes in the composition of the capacitive electrical double layer for 1-ethyl-3 methylimidazolium tris(pentafluoroethyl)-trifluorophosphate, an ionic liquid, in contact with a gold electrode surface as a function of potential. The mass difference between the cation and anion means that the technique can effectively "weigh" the surface charge accurately with high temporal resolution. This reveals quantitatively how changing the potential alters the ratio of cations and anions associated with the electrode surface, and thus the charge per unit area, as well as the kinetics associated with these interfacial processes. The measurements reveal that it is diffusion of co-ions into the interfacial region rather than expulsion of counterions that controls the relaxation. The measured potential dependent double layer capacitance experimentally validates recent theoretical predictions for counterion overscreening (low potentials) and crowding (high potentials) at electrode surfaces. This new capacity to quantitatively measure ion composition is critical for ionic liquid applications ranging from batteries, capacitors and electrodeposition through to boundary layer structure in tribology, and more broadly provides new insight into interfacial processes in concentrated electrolyte solutions. PMID- 26370451 TI - A probabilistic topic model for clinical risk stratification from electronic health records. AB - BACKGROUND AND OBJECTIVE: Risk stratification aims to provide physicians with the accurate assessment of a patient's clinical risk such that an individualized prevention or management strategy can be developed and delivered. Existing risk stratification techniques mainly focus on predicting the overall risk of an individual patient in a supervised manner, and, at the cohort level, often offer little insight beyond a flat score-based segmentation from the labeled clinical dataset. To this end, in this paper, we propose a new approach for risk stratification by exploring a large volume of electronic health records (EHRs) in an unsupervised fashion. METHODS: Along this line, this paper proposes a novel probabilistic topic modeling framework called probabilistic risk stratification model (PRSM) based on Latent Dirichlet Allocation (LDA). The proposed PRSM recognizes a patient clinical state as a probabilistic combination of latent sub profiles, and generates sub-profile-specific risk tiers of patients from their EHRs in a fully unsupervised fashion. The achieved stratification results can be easily recognized as high-, medium- and low-risk, respectively. In addition, we present an extension of PRSM, called weakly supervised PRSM (WS-PRSM) by incorporating minimum prior information into the model, in order to improve the risk stratification accuracy, and to make our models highly portable to risk stratification tasks of various diseases. RESULTS: We verify the effectiveness of the proposed approach on a clinical dataset containing 3463 coronary heart disease (CHD) patient instances. Both PRSM and WS-PRSM were compared with two established supervised risk stratification algorithms, i.e., logistic regression and support vector machine, and showed the effectiveness of our models in risk stratification of CHD in terms of the Area Under the receiver operating characteristic Curve (AUC) analysis. As well, in comparison with PRSM, WS-PRSM has over 2% performance gain, on the experimental dataset, demonstrating that incorporating risk scoring knowledge as prior information can improve the performance in risk stratification. CONCLUSIONS: Experimental results reveal that our models achieve competitive performance in risk stratification in comparison with existing supervised approaches. In addition, the unsupervised nature of our models makes them highly portable to the risk stratification tasks of various diseases. Moreover, patient sub-profiles and sub-profile-specific risk tiers generated by our models are coherent and informative, and provide significant potential to be explored for the further tasks, such as patient cohort analysis. We hypothesize that the proposed framework can readily meet the demand for risk stratification from a large volume of EHRs in an open-ended fashion. PMID- 26370452 TI - Providing care at home will not save money for NHS in next five years, Monitor says. PMID- 26370453 TI - Impact of Acquired von Willebrand Syndrome in Severe Aortic Stenosis. PMID- 26370454 TI - Optimal Treatment using Statins from Childhood in Heterozygous Familial Hypercholesterolemia. PMID- 26370455 TI - Role of the Atg9a gene in intrauterine growth and survival of fetal mice. AB - Autophagy is activated by environment unfavorable for survival and requires Atg9a protein. Mice heterozygous for p57(Kip2), devoid of the imprinted paternal allele (p57(Kip2+/-)), are known to develop hypertension during pregnancy. To determine whether fetal Atg9a is involved in the intrauterine survival and growth of fetal mice, this study was performed on Atg9a heterozygous (Atg9a(+/-)) pregnant mice with and without p57(Kip2+/-). The pregnant mice heterozygous for both knockout alleles of Atg9a and p57(Kip2) (Atg9a(+/-)/p57(Kip2+/-)), but not those heterozygous for Atg9a alone, developed hypertension during pregnancy. Placental expression of Atg9a mRNA was significantly decreased in the Atg9a(-/-) mice compared to Atg9a(+/-) or Atg9a(+/+) mice. The Atg9a(-/-) fetal mice exhibited significantly retarded growth and were more likely to die in utero compared to Atg9a(+/+) and Atg9a(+/-) fetal mice. Growth retardation was observed in the presence of maternal hypertension in Atg9a(-/-) fetal mice. These results suggest that Atg9a(-/-) fetal mice from pregnant dams heterozygous for both knockout alleles of Atg9a and p57(Kip2) are more susceptible to hypertensive stress than fetuses with intact autophagic machinery. PMID- 26370456 TI - The effects of tacrolimus on the activity and expression of tissue factor in the rat ovary with ischemia-reperfusion induced injury. AB - In the present study, the effects of tacrolimus on the activity and expression of tissue factor (TF) were investigated in the ovarian ischemia-reperfusion induced injury in rats. Twenty-eight female rats (8-12 weeks, 300-350 g) were divided into four groups: control, ischemia-reperfusion (IR), tacrolimus treated before ischemia (TBI), and tacrolimus treated before reperfusion (TBR) groups (n=7/per group). TF activity was measured using Quick's method, whereas TF expression was examined immunohistochemically. TF activity was significantly higher in all treated groups compared with the control group. Strong ovarian TF expression was demonstrated in the IR and TBR groups. Moreover, tacrolimus decreased TF activity in the TBI group compared with the IR group. The decreased activity of TF in the ovarian IR model may prevent IR-related inflammation during transplant procedure. PMID- 26370457 TI - Interferon-gamma differentially modulates the impact of tumor necrosis factor alpha on human endometrial stromal cells. AB - The pro-inflammatory T helper (Th)-1 cytokines, tumor necrosis factor-alpha (TNF alpha) and interferon-gamma (IFN-gamma), are immunological factors relevant at the feto-maternal interface and involved in the pathophysiology of implantation disorders. The synergistic action of the two cytokines has been described with regard to apoptotic cell death and inflammatory responses in different cell types, but little is known regarding the human endometrium. Therefore, we examined the interaction of TNF-alpha and IFN-gamma in human endometrial stromal cells (ESCs). ESCs were isolated from specimens obtained during hysterectomy and decidualized in vitro. Cells were incubated with TNF-alpha, IFN-gamma or signaling-inhibitor. Insulin-like growth factor binding protein (IGFBP)-1, prolactin (PRL), leukemia inhibitory factor (LIF), interleukin (IL)-6, IL-8, regulated on activation normal T-cell expressed and secreted protein (RANTES) and monocyte chemotactic protein (MCP)-1 were measured using ELISA and real-time RT PCR. Nuclear factor of transcription (NF)-kappaB and its inhibitor (IkappaBalpha) were analyzed by in-cell western assay and transcription factor assay. TNF-alpha inhibited and IFN-gamma did not affect the decidualization of ESCs. In contrast, IFN-gamma differentially modulated the stimulating effect of TNF-alpha on cytokines by enhancing IL-6, RANTES and MCP-1 and attenuating LIF mRNA expression. These effects were time- and dose-dependent. IFN-gamma had no impact on the initial activation of NF-kappaB signaling. Histone-deacetylase activity was involved in the modulating effect of IFN-gamma on RANTES secretion. These observations showed a distinct pattern of interaction of the Th-1 cytokines, TNF alpha and IFN-gamma in the human endometrium, which could play an important role in the pathophysiology of implantation disorders. PMID- 26370458 TI - Effects of sperm pretreatment and embryo activation methods on the development of bovine embryos produced by intracytoplasmic sperm injection. AB - The aim of the study was to examine the effects of different embryo activation methods and sperm pretreatments on the activation and development of bovine embryos produced by intracytoplasmic sperm injection (ICSI). Four activation agents, i.e., calcium ionophore (A23187), ionomycin (Ion), electric pulse (EP) and ethanol (Eth) were used in various combinations to activate bovine ICSI embryos. The normal fertilization rate was similar in bovine ICSI embryos activated by A23187+Eth, Ion+Eth, Ion+EP+Eth, and 2-Ion (Ion administered two times)+Eth. Increasing the frequency of ionomycin stimulation from two (2 Ion+Eth) to three times (3-Ion+Eth) significantly (p<0.05) increased the cell number per embryo at the blastocyst stage. In addition, spermatozoa were pretreated with dithiothreitol (DTT), glutathione (GSH) or GSH+lysolecithin (LL) and used for producing bovine ICSI embryos. The blastocyst rate of bovine ICSI embryos produced from sperm pretreated with GSH was significantly (p<0.05) higher than those of embryos produced from sperm pretreated with DTT and GSH+LL. In conclusion, the embryo activation methods and sperm pretreatments examined in the present study did not affect the normal fertilization rate of bovine ICSI embryos. However, activation with 3-Ion+Eth and sperm pretreatment with GSH increased the cell number per embryo at blastocyst stage and the blastocyst rate, respectively, in bovine ICSI embryos. PMID- 26370459 TI - Low-dose exposure to di-(2-ethylhexyl) phthalate (DEHP) increases susceptibility to testicular autoimmunity in mice. AB - Exposure to di-(2-ethylhexyl) phthalate (DEHP) induces spermatogenic disturbance (SD) through oxidative stress, and affects the immune system by acting as an adjuvant. Recently, we reported that in mice, a low dose of DEHP, which did not affect spermatogenesis, was able to alter the testicular immune microenvironment. Experimental autoimmune orchitis (EAO) can be induced by repeated immunization with testicular antigens, and its pathology is characterized by production of autoantibodies and SD. In the present study, we investigated the effect of a low dose DEHP on the susceptibility of mice to EAO. The exposure to DEHP-containing feed (0.01%) caused a modest functional damage to the blood-testis barrier (BTB) with an increase in testicular number of interferon gamma (IFN-gamma)-positive cells and resulted in the production of autoantibodies targeting haploid cells, but did not affect spermatogenesis. While only single immunization with testicular antigens caused very mild EAO, the concurrent DEHP exposure induced severe EAO with significant increases in number of interferon gamma-positive cells and macrophages, as well as lymphocytic infiltration and serum autoantibody titer accompanied by severe SD. To summarize, the exposure of mice to the low dose DEHP does not induce significant SD, but it may cause an increase in IFN gamma positive cells and modest functional damage to the BTB in the testis. These changes lead to an autoimmune response against haploid cell autoantigens, resulting in increased susceptibility to EAO. PMID- 26370460 TI - Silymarin and protein kinase A inhibitor modulate glucose-mediated mouse sperm motility: An in vitro study. AB - Glucose is suggested to play a key role in motility hyperactivation of mammalian spermatozoa. The current study aimed to investigate the modulatory effects of silymarin and/or a protein kinase A (PKA) inhibitor (H-89) on glucose-mediated motility parameters of mouse spermatozoa. Spermatozoa were incubated in HEPES medium containing normal (NG; 5.5mM) or high (HG; 25 mM) glucose concentration. The results of computer-assisted analysis showed that samples incubated in HG resulted in a larger (p < 0.05) percentage of motile spermatozoa at 120 min (59.5 +/- 14.8% vs. 34.0 +/- 4.4%) compared to those incubated in NG. The average pathway velocity (VAP), curvilinear velocity (VCL), and straight-line velocity (VSL) exhibited similar patterns at 60 and 120 min when incubated in HG (p < 0.05). Treatments with silymarin (5, 10, 20 MUg/mL) did not significantly affect sperm motility under NG conditions, but decreased the HG-enhanced motility, VAP, and VCL at 120 min (p < 0.05). H-89 (30 MUM) reduced (p < 0.05) motility at 30 min examined in the NG or HG medium. At 90 min, H-89 also reduced (p < 0.05) the HG-enhanced motility of spermatozoa incubated with or without 20 MUg/mL silymarin by 49% or 32%, respectively. In conclusion, the H-89-inhibition of glucose mediated mouse sperm motility and certain types of velocity suggests that the glycolysis-PKA pathway is involved in the regulation of sperm motility. Silymarin may maintain sperm motility under NG conditions, but it inhibits glucose activated sperm motility. PMID- 26370461 TI - Organic cation/carnitine transporter OCTN2 (SLC22A5) -207C>G (rs2631367) polymorphism is not associated with male infertility. AB - Carnitine is an important factor in the initiation of progressive sperm motility and end stage of sperm maturation. The compound is transported by an organic cation/carnitine transporter (OCTN2), which is expressed in the male reproductive system. OCTN2 is encoded by SLC22A5 gene with proven -207C>G functional polymorphism. The aim of the case-control study was to investigate a potential association between the -207C>G SLC22A5 polymorphism and male infertility. The 207C>G SLC22A5 polymorphism was determined by means of TaqMan assay in 206 infertile Caucasian males and 256 ethnically matched controls. Besides genotyping study, sperm mitochondrial function was assessed using NADH-dependent NBT assay. The distribution of SLC22A5 genotypes in infertile men was as follows: CC - 29.6%, CG - 53.9%, GG - 16.5% and in fertile men: CC - 32.0%, CG - 50.0%, GG - 18.0%, and was comparable in both evaluated groups. Likewise, the studied polymorphism did not affect sperm mitochondrial function. The results of the current study demonstrated that -207C>G polymorphism of the SLC22A5 gene is not associated with male infertility. PMID- 26370462 TI - Reproductive traits of the spirlin Alburnoides bipunctatus in the Vistula River basin. AB - The aim of the current study was to examine whether environmental conditions may explain interpopulation variation in fecundity and egg size of the spirlin from two rivers of the Vistula River basin. The obtained results indicated that the reproductive performance, including the gonadosomatic index, was similar in both rivers and fecundity increased with total length of females. The observed differences in water temperatures and flow speed between the rivers were too small to cause discernible differences in the reproductive performance of fish. PMID- 26370463 TI - Characterization of ovulatory capacity development in the dominant follicle of dromedary camels (Camelus dromedarius). AB - The acquisition of ovulatory capacity in the growing dominant follicle (DF) of dromedary camels was examined in the current study. Ovulation occurred in response to hCG (1500 IU) in 27.3%, 58.3% or 100% of camels with follicles of 9, 10 or 11 mm diameter, respectively. A high dose of hCG (4500 IU) resulted in ovulation of 77.8% and 100% of camels with follicles of 9 and 10mm, respectively. In naturally mated animals, ovulation occurred in 36.4% and 92.8% of camels with 10 and 11 mm follicles, respectively. PMID- 26370465 TI - The complete mitochondrial genome of the moss Oxystegus tenuirostris (Hook. & Taylor) A.J.E. Sm. (Pottiaceae, Bryophyta). AB - The mitochondrial genome of mosses is characterized by a highly conserved structure and genic content. This is confirmed here through the assembly and annotation of the mt genome of the moss Oxystegus tenuirostris, family Pottiaceae, for which it is assembled. A phylogenetic tree is inferred from the whole genome of 16 species of mosses to validate the sequence of O. tenuirostris by confirming its shared ancestry with Syntrichia. The genome is 105 001 bp long, with a GC content of 39.2%, comprising 40 protein coding, 24 tRNA, and 3 rRNA genes. All introns reported from the mt genome of all but one peristomate moss are present, whereas no region of 50 bp or more is repeated within the genome. The genic content and order is identical to that of most mosses, highlighting that the mt genome is static not only across the phylogenetic depth but also breadth of the moss tree of life. PMID- 26370464 TI - Autologous peripheral blood stem cell mobilization following dose-adjusted cyclophosphamide, doxorubicin, vincristine, and prednisolone chemotherapy alone or in combination with rituximab in treating high-risk non-Hodgkin's lymphoma. AB - BACKGROUND: The regimen of cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) is an efficient treatment of non-Hodgkin's lymphoma (NHL). This study aimed to assess the efficacy and toxicity of dose-adjusted CHOP alone or in combination with rituximab (R-CHOP) by examining the stem cell mobilization in NHL patients. Factors affecting the collection of CD34+ cells were also explored. METHODS: Our retrospective study included 39 patients eligible for autologous stem cell transplantation: 14 patients who expressed CD20 and were financially eligible received R-CHOP for autologous peripheral blood stem cell (APBSC) mobilization; the remaining 25 patients received CHOP. RESULTS: The median CD34+ cell yield was 7.01*10(6) cells/kg body weight (range 1.49 28.39*10(6) cells/kg body weight), with only two patients failing to meet the target CD34+ cell harvest of >=2.0*10(6) cells/kg body weight. The median number of apheresis procedures per patient was 1 (range 1-3). The APBSC mobilization yield of the CHOP group appeared to be higher than that of the R-CHOP group (P=0.005), whereas the success rate was similar between groups. R-CHOP elevated the complete response (CR) rate in B cell lymphoma patients as compared with CHOP (P=0.01). No significant differences in toxicity or engraftment were observed between the two groups. CONCLUSION: The present study demonstrated that dose adjusted CHOP chemotherapy effectively mobilized APBSCs in NHL patients and that the addition of rituximab to dose-adjusted CHOP chemotherapy elevated the CR rate for patients with B-cell lymphoma. PMID- 26370466 TI - Remote ischaemic pre-conditioning for the prevention of acute kidney injury. AB - Acute kidney injury (AKI) is a common complication associated with high morbidity and mortality in hospitalized patients. One potential mechanism underlying renal injury is ischaemia/reperfusion injury (IRI), which attributed the organ damage to the inflammatory and oxidative stress responses induced by a period of renal ischaemia and subsequent reperfusion. Therapeutic strategies that aim at minimizing the effect of IRI on the kidneys may prevent AKI and improve clinical outcomes significantly. In this review, we examine the technique of remote ischaemic preconditioning (rIPC), which has been shown by several trials to confer organ protection by applying transient, brief episodes of ischaemia at a distant site before a larger ischaemic insult. We provide an overview of the current clinical evidence regarding the renoprotective effect of rIPC in the key clinical settings of cardiac or vascular surgery, contrast-induced AKI, pre existing chronic kidney disease (CKD) and renal transplantation, and discuss key areas for future research. PMID- 26370467 TI - Constant light enhances synchrony among circadian clock cells and promotes behavioral rhythms in VPAC2-signaling deficient mice. AB - Individual neurons in the suprachiasmatic nuclei (SCN) contain an intracellular molecular clock and use intercellular signaling to synchronize their timekeeping activities so that the SCN can coordinate brain physiology and behavior. The neuropeptide vasoactive intestinal polypeptide (VIP) and its VPAC2 receptor form a key component of intercellular signaling systems in the SCN and critically control cellular coupling. Targeted mutations in either the intracellular clock or intercellular neuropeptide signaling mechanisms, such as VIP-VPAC2 signaling, can lead to desynchronization of SCN neuronal clocks and loss of behavioral rhythms. An important goal in chronobiology is to develop interventions to correct deficiencies in circadian timekeeping. Here we show that extended exposure to constant light promotes synchrony among SCN clock cells and the expression of ~24 h rhythms in behavior in mice in which intercellular signaling is disrupted through loss of VIP-VPAC2 signaling. This study highlights the importance of SCN synchrony for the expression of rhythms in behavior and reveals how non-invasive manipulations in the external environment can be used to overcome neurochemical communication deficits in this important brain system. PMID- 26370468 TI - The cerebral correlates of subliminal emotions: an eleoencephalographic study with emotional hybrid faces. AB - In a high-resolution electroencephalographic study, participants evaluated the friendliness level of upright and inverted 'hybrid faces', i.e. facial photos containing a subliminal emotional core in the low spatial frequencies (< 6 cycles/image), superimposed on a neutral expression in the rest of the spatial frequencies. Upright happy and angry faces were judged as more friendly or less friendly than neutral faces, respectively. We observed the time course of cerebral correlates of these stimuli with event-related potentials (ERPs), confirming that hybrid faces elicited the posterior emotion-related and face related components (P1, N170 and P2), previously shown to be engaged by non subliminal emotional stimuli. In addition, these components were stronger in the right hemisphere and were both enhanced and delayed by face inversion. A frontal positivity (210-300 ms) was stronger for emotional than for neutral faces, and for upright than for inverted faces. Hence, hybrid faces represent an original approach in the study of subliminal emotions, which appears promising for investigating their electrophysiological correlates. PMID- 26370469 TI - Downregulation of NOB1 inhibits proliferation and promotes apoptosis in human oral squamous cell carcinoma. AB - NIN1/RPN12 binding protein 1 homolog (NOB1) facilitates the maturation of the 20S proteasome and is then degraded by 26S proteasome to complete 26S proteasome biogenesis. It also accompanies the pre-40S ribosomes during nuclear export and is cleaved at D-site of 20S pre-rRNA to form mature 18S rRNA in growing cells. NOB1 was reported to be involved in the development of several types of cancer. However, the role of NOB1 in oral squamous cell carcinoma (OSCC) has not been addressed. In the present study, the expression of NOB1 in 50 OSCC patients with different genders, ages, TNM and pathological grades was detected using immunohistochemistry and western blotting. A loss-of-function study was carried out by the lentivirus-mediated siRNA knockdown of NOB1 in the CAL27 and TCA-8113 OSCC cell lines. The results showed that, NOB1 expression increased with pathological grades. In the CAL27 and TCA-8113 cell lines, knockdown of NOB1 in OSCC cells decreased cell proliferation, colony formation, increased cell apoptosis and also induced cell cycle arrest in the S phase. The results suggested that NOB1 is important in OSCC development and serves as a candidate indicator of aggressiveness and a therapeutic target of OSCC. PMID- 26370470 TI - Identifying types of sex conversations in adolescent health maintenance visits. AB - Background Physician-adolescent sexuality discussions are a recommended element in health maintenance visits, but such discussions - if they occur at all - probably vary by adolescents' characteristics and situations, and physicians' personal beliefs and training. However, little is known about the form and content of physician-adolescent sexuality discussions during health maintenance visits. METHODS: We evaluated 245 physician-adolescent sexuality conversations. Using latent class analysis, we identified conversation types based on 13 sexually related topics, which occurred in at least 10% of all conversations. RESULTS: We found four discrete types of sexuality conversations, which differed in terms of emphasis, topics addressed as part of the sexual history and risk assessment, and topics addressed in anticipatory guidance. Inquiry about partnered sexual experience was typical across all conversation types, as well as over half including discussions about body development and protective behaviours. In all four types of conversation, sexuality discussions were typically embedded in a sequence of psychosocial and behavioural topics recommended for health maintenance visits. CONCLUSIONS: The presence of sexuality conversations in the majority of these visits suggests that physicians consider sexuality to be an important issue and part of their responsibility in caring for their adolescent patients. However, the substantial variability in the types of sexuality conversations, particularly the notable omissions of many key topics, supports the importance of teaching sexual health interview skills in medical school and residency, and as part of continuing medical education and quality improvement. PMID- 26370471 TI - Genomic investigations of evolutionary dynamics and epistasis in microbial evolution experiments. AB - Microbial evolution experiments enable us to watch adaptation in real time, and to quantify the repeatability and predictability of evolution by comparing identical replicate populations. Further, we can resurrect ancestral types to examine changes over evolutionary time. Until recently, experimental evolution has been limited to measuring phenotypic changes, or to tracking a few genetic markers over time. However, recent advances in sequencing technology now make it possible to extensively sequence clones or whole-population samples from microbial evolution experiments. Here, we review recent work exploiting these techniques to understand the genomic basis of evolutionary change in experimental systems. We first focus on studies that analyze the dynamics of genome evolution in microbial systems. We then survey work that uses observations of sequence evolution to infer aspects of the underlying fitness landscape, concentrating on the epistatic interactions between mutations and the constraints these interactions impose on adaptation. PMID- 26370476 TI - Device therapy: Leadless pacemaker demonstrates safety, efficacy, and retrievability. PMID- 26370473 TI - Pathophysiology and clinical evaluation of acute heart failure. AB - Acute heart failure (AHF) is a complex syndrome characterized by worsening heart failure (HF) symptoms that requires escalation of therapy. Intrinsic cardiac abnormalities and comorbid conditions, including lung and renal disease, and sleep-disordered breathing, can contribute to the development of AHF. In this Review, we summarize and discuss the literature on the clinical evaluation and underlying pathophysiology of AHF. Important features of AHF evaluation include identification of precipitating factors to the disease, and assessment of circulatory-renal limitations associated with use of HF medications, prior HF hospitalizations, congestion and perfusion profiles, and end-organ dysfunction. The pathophysiological contributions of endothelial dysfunction, neurohormonal activation, venous congestion, and myocardial injury to the development of AHF are also discussed. These potential causative mechanisms provide a framework for clinicians to evaluate and manage patients with AHF and highlight possible future targets for therapies designed to improve clinical outcomes. PMID- 26370477 TI - Hypertension: Initial combination therapy improves PAH. PMID- 26370478 TI - Arrhythmias: Results from the WEARIT-II registry. PMID- 26370480 TI - Pharmacotherapy: Lack of benefit of cyclosporine to attenuate reperfusion injury after PCI. PMID- 26370483 TI - Antiplatelet therapy: Benefits of extended DAPT after MI. PMID- 26370484 TI - Acute coronary syndromes: Bivalirudin versus heparin for ACS. PMID- 26370485 TI - Acute coronary syndromes: Utility of measuring fractional flow reserve by CT angiography in patients with suspected CAD. PMID- 26370486 TI - Interventional cardiology: Absorbable scaffolds noninferior to metallic stents at 1 year. PMID- 26370487 TI - [Eosinophilic pleuritic: An unusual complication of treatment with an angiotensin converting enzyme inhibitor]. AB - BACKGROUND: Eosinophilic pleural effusions are defined by an eosinophil count >=10% in pleural fluid and represent approximately 10% of exudative pleural effusions. OBSERVATION: We report the first case of eosinophilic pleural effusion occurring due to lisinopril treatment. Improvement after drug discontinuation and recurrence after reintroduction indicated that lisinopril was responsible for the effusion. CONCLUSION: The main causes of eosinophilic pleural effusions are infections including tuberculosis, and malignancies. Drug-induced eosinophilic pleural effusions have only rarely been described, mainly caused by cardiovascular or neuropsychiatric medicines. PMID- 26370488 TI - [Hypermetabolic pulmonary nodules of unusual etiology]. PMID- 26370489 TI - Sinonasal fibrosarcoma: analysis of the Surveillance, Epidemiology, and End Results database. AB - BACKGROUND: Primary fibrosarcoma of the sinonasal region is an infrequently occurring malignant neoplasm. Fibrosarcomas are most commonly found in the extremities, with only 1% of fibrosarcomas reported in the head and neck region. This study analyzes the demographic, clinicopathologic, and survival characteristics of sinonasal fibrosarcoma (SNFS). METHODS: The Surveillance, Epidemiology, and End Results (SEER) database (1973 to 2012) was queried for SNFS cases. Data were analyzed with respect to various demographic and clinicopathologic factors. Survival was analyzed using the Kaplan-Meier model. RESULTS: Fifty-one cases of fibrosarcoma were identified in the sinonasal region. The mean age at diagnosis was 54.5 years and the mean survival was 119.7 months. There was no gender predilection with a male-to-female ratio of 1.04:1. The maxillary sinus was the most common site of involvement (54.9%), followed by the nasal cavity (23.5%). Five-year survival analysis revealed an overall survival rate of 71.7%, disease-specific survival rate of 77.8%, and relative survival (RS) rate of 78.8%. Disease-specific survival was better among those treated with surgery (with [76.2%] or without [87.5%] adjuvant radiotherapy) than those treated with primary radiotherapy alone (33.3%) (p = 0.0069). CONCLUSION: SNFS is a rare entity. This study represents the largest series of SNFS to date. The mainstay of treatment for this tumor is surgical resection with or without radiotherapy. PMID- 26370490 TI - Convergence beyond flower morphology? Reproductive biology of hummingbird pollinated plants in the Brazilian Cerrado. AB - Convergent reproductive traits in non-related plants may be the result of similar environmental conditions and/or specialised interactions with pollinators. Here, we documented the pollination and reproductive biology of Bionia coriacea (Fabaceae), Esterhazya splendida (Orobanchaceae) and Ananas ananassoides (Bromeliaceae) as case studies in the context of hummingbird pollination in Cerrado, the Neotropical savanna of Central South America. We combined our results with a survey of hummingbird pollination studies in the region to investigate the recently suggested association of hummingbird pollination and self-compatibility. Plant species studied here differed in their specialisation for ornithophily, from more generalist A. ananassoides to somewhat specialist B. coriacea and E. splendida. This continuum of specialisation in floral traits also translated into floral visitor composition. Amazilia fimbriata was the most frequent pollinator for all species, and the differences in floral display and nectar energy availability among plant species affect hummingbirds' behaviour. Most of the hummingbird-pollinated Cerrado plants (60.0%, n = 20), including those studied here, were self-incompatible, in contrast to other biomes in the Neotropics. Association to more generalist, often territorial, hummingbirds, and resulting reduced pollen flow in open savanna areas may explain predominance of self-incompatibility. But it is possible that mating system is more associated with the predominance of woody hummingbird plants in the Cerrado plant assemblage than to the pollination system itself. PMID- 26370491 TI - Effect of vitamin D on clinical and biochemical parameters in polycystic ovary syndrome women: A meta-analysis. AB - AIM: Using a meta-analysis framework, we investigated the association between the serum level of vitamin D and the risk of polycystic ovary syndrome (PCOS) and further examined the therapeutic effect of vitamin D on the clinical features of PCOS. MATERIAL AND METHODS: Multiple databases were searched to retrieve studies. We chose clinical studies that investigated the relation between the serum level of vitamin D and the risk of PCOS or the therapeutic effect of vitamin D on PCOS. The search results were screened according to strict inclusion and exclusion criteria to select high-quality studies for inclusion. Statistical analyses were carried out using stata 12.0. RESULTS: Seventeen studies were eligible in this meta-analysis. The levels of 25-hydroxyvitamin D and the quantitative insulin sensitivity check index in the PCOS group were remarkably lower than in the controls, whereas the homeostasis model assessment of insulin resistance in the PCOS group was markedly higher than in the controls. No statistically significant difference was observed in serum parathyroid hormone levels between the two groups. The 25-hydroxyvitamin D levels were significantly elevated after PCOS patients received vitamin D3 treatment, but serum parathyroid hormone concentration, homeostasis model assessment of insulin resistance and quantitative insulin-sensitivity check index did not show any significant changes, indicating a lack of therapeutic response. CONCLUSION: Our results suggest that the serum level of vitamin D is associated with the risk of PCOS, but the therapeutic effect of vitamin D on PCOS remains to be further explored. PMID- 26370493 TI - Phosphinic Amide as Directing Group Enabling Palladium(II)-Catalyzed ortho C-H Alkenylation of Anilines without and with Alkylation at the Nitrogen Atom. AB - A phosphinic amide is introduced as a directing group for the ortho C-H alkenylation of anilines. The new donor group distinguishes itself from existing ones by assisting the C-H bond activation of anilides without (NH group) and with alkylation (NMe group) at the amide nitrogen atom. The reactivity is even reversed with the methyl-substituted anilide being more reactive than its unsubstituted counterpart. Electron-donating substituents at the arene ring enhance their reactivity while halogenation is not tolerated. The phosphinic amide also enables the C-7-selective C-H alkenylation of indoline. PMID- 26370492 TI - Borrelia burgdorferi HtrA: evidence for twofold proteolysis of outer membrane protein p66. AB - In prokaryotes, members of the High Temperature Requirement A (HtrA) family of serine proteases function in the periplasm to degrade damaged or improperly folded membrane proteins. Borrelia burgdorferi, the agent of Lyme disease, codes for a single HtrA homolog. Two-dimensional electrophoresis analysis of B. burgdorferi B31A3 and a strain that overexpresses HtrA (A3HtrAOE) identified a downregulated protein in A3HtrAOE with a mass, pI and MALDI-TOF spectrum consistent with outer membrane protein p66. P66 and HtrA from cellular lysates partitioned into detergent-resistant membranes, which contain cholesterol glycolipid-rich membrane regions known as lipid rafts, suggesting that HtrA and p66 may reside together in lipid rafts also. This agrees with previous work from our laboratory, which showed that HtrA and p66 are constituents of B. burgdorferi outer membrane vesicles. HtrA degraded p66 in vitro and A3HtrAOE expressed reduced levels of p66 in vivo. Fluorescence confocal microscopy revealed that HtrA and p66 colocalize in the membrane. The association of HtrA and p66 establishes that they could interact efficiently and their protease/substrate relationship provides functional relevance to this interaction. A3HtrAOE also showed reduced levels of p66 transcript in comparison with wild-type B31A3, indicating that HtrA-mediated regulation of p66 may occur at multiple levels. PMID- 26370494 TI - Altered emotion regulation in obsessive-compulsive disorder as evidenced by the late positive potential. AB - BACKGROUND: Obsessive-compulsive disorder (OCD) is associated with marked anxiety, which triggers repetitive behaviours or mental rituals. The persistence of pathological anxiety and maladaptive strategies to reduce anxiety point to altered emotion regulation. The late positive potential (LPP) is an event-related brain potential (ERP) that reflects sustained attention to emotional stimuli and is sensitive to emotion-regulation instructions. We hypothesized that patients with OCD show altered electrocortical responses during reappraisal of stimuli triggering their symptoms. METHOD: To test our hypothesis, ERPs to disorder relevant, generally aversive and neutral pictures were recorded while participants were instructed to either maintain or reduce emotional responding using cognitive distraction or cognitive reappraisal. RESULTS: Relative to healthy controls, patients with OCD showed enhanced LPPs in response to disorder relevant pictures, indicating their prioritized processing. While both distraction and reappraisal successfully reduced the LPP in healthy controls, patients with OCD failed to show corresponding LPP modulation during cognitive reappraisal despite successfully reduced subjective arousal ratings. CONCLUSIONS: The results point to sustained attention towards emotional stimuli during cognitive reappraisal in OCD and suggest that abnormal emotion regulation should be integrated in models of OCD. PMID- 26370495 TI - Jeffrey Fredberg: Flow under pressure. PMID- 26370496 TI - Sorting out endosome form and function. PMID- 26370498 TI - ER-mitochondrial junctions can be bypassed by dominant mutations in the endosomal protein Vps13. AB - The endoplasmic reticulum-mitochondria encounter structure (ERMES) complex tethers the endoplasmic reticulum and the mitochondria. It is thought to facilitate interorganelle lipid exchange and influence mitochondrial dynamics and mitochondrial DNA maintenance. Despite this important role, ERMES is not found in metazoans. Here, we identified single amino acid substitutions in Vps13 (vacuolar protein sorting 13), a large universally conserved eukaryotic protein, which suppress all measured phenotypic consequences of ERMES deficiency. Combined loss of VPS13 and ERMES is lethal, indicating that Vps13 and ERMES function in redundant pathways. Vps13 dynamically localizes to vacuole-mitochondria and to vacuole-nucleus contact sites depending on growth conditions, suggesting that ERMES function can be bypassed by the activity of other contact sites, and that contact sites establish a growth condition-regulated organelle network. PMID- 26370497 TI - MST kinases in development and disease. AB - The mammalian MST kinase family, which is related to the Hippo kinase in Drosophila melanogaster, includes five related proteins: MST1 (also called STK4), MST2 (also called STK3), MST3 (also called STK24), MST4, and YSK1 (also called STK25 or SOK1). MST kinases are emerging as key signaling molecules that influence cell proliferation, organ size, cell migration, and cell polarity. Here we review the regulation and function of these kinases in normal physiology and pathologies, including cancer, endothelial malformations, and autoimmune disease. PMID- 26370499 TI - KLP-7 acts through the Ndc80 complex to limit pole number in C. elegans oocyte meiotic spindle assembly. AB - During oocyte meiotic cell division in many animals, bipolar spindles assemble in the absence of centrosomes, but the mechanisms that restrict pole assembly to a bipolar state are unknown. We show that KLP-7, the single mitotic centromere associated kinesin (MCAK)/kinesin-13 in Caenorhabditis elegans, is required for bipolar oocyte meiotic spindle assembly. In klp-7(-) mutants, extra microtubules accumulated, extra functional spindle poles assembled, and chromosomes frequently segregated as three distinct masses during meiosis I anaphase. Moreover, reducing KLP-7 function in monopolar klp-18(-) mutants often restored spindle bipolarity and chromosome segregation. MCAKs act at kinetochores to correct improper kinetochore-microtubule (k-MT) attachments, and depletion of the Ndc-80 kinetochore complex, which binds microtubules to mediate kinetochore attachment, restored bipolarity in klp-7(-) mutant oocytes. We propose a model in which KLP 7/MCAK regulates k-MT attachment and spindle tension to promote the coalescence of early spindle pole foci that produces a bipolar structure during the acentrosomal process of oocyte meiotic spindle assembly. PMID- 26370500 TI - Asymmetric cell division during T cell development controls downstream fate. AB - During mammalian T cell development, the requirement for expansion of many individual T cell clones, rather than merely expansion of the entire T cell population, suggests a possible role for asymmetric cell division (ACD). We show that ACD of developing T cells controls cell fate through differential inheritance of cell fate determinants Numb and alpha-Adaptin. ACD occurs specifically during the beta-selection stage of T cell development, and subsequent divisions are predominantly symmetric. ACD is controlled by interaction with stromal cells and chemokine receptor signaling and uses a conserved network of polarity regulators. The disruption of polarity by deletion of the polarity regulator, Scribble, or the altered inheritance of fate determinants impacts subsequent fate decisions to influence the numbers of DN4 cells arising after the beta-selection checkpoint. These findings indicate that ACD enables the thymic microenvironment to orchestrate fate decisions related to differentiation and self-renewal. PMID- 26370501 TI - Structures of the yeast dynamin-like GTPase Sey1p provide insight into homotypic ER fusion. AB - Homotypic membrane fusion of the endoplasmic reticulum is mediated by dynamin like guanosine triphosphatases (GTPases), which include atlastin (ATL) in metazoans and Sey1p in yeast. In this paper, we determined the crystal structures of the cytosolic domain of Sey1p derived from Candida albicans. The structures reveal a stalk-like, helical bundle domain following the GTPase, which represents a previously unidentified configuration of the dynamin superfamily. This domain is significantly longer than that of ATL and critical for fusion. Sey1p forms a side-by-side dimer in complex with GMP-PNP or GDP/AlF4(-) but is monomeric with GDP. Surprisingly, Sey1p could mediate fusion without GTP hydrolysis, even though fusion was much more efficient with GTP. Sey1p was able to replace ATL in mammalian cells, and the punctate localization of Sey1p was dependent on its GTPase activity. Despite the common function of fusogenic GTPases, our results reveal unique features of Sey1p. PMID- 26370502 TI - Prosaposin facilitates sortilin-independent lysosomal trafficking of progranulin. AB - Mutations in the progranulin (PGRN) gene have been linked to two distinct neurodegenerative diseases, frontotemporal lobar degeneration (FTLD) and neuronal ceroid lipofuscinosis (NCL). Accumulating evidence suggests a critical role of PGRN in lysosomes. However, how PGRN is trafficked to lysosomes is still not clear. Here we report a novel pathway for lysosomal delivery of PGRN. We found that prosaposin (PSAP) interacts with PGRN and facilitates its lysosomal targeting in both biosynthetic and endocytic pathways via the cation-independent mannose 6-phosphate receptor and low density lipoprotein receptor-related protein 1. PSAP deficiency in mice leads to severe PGRN trafficking defects and a drastic increase in serum PGRN levels. We further showed that this PSAP pathway is independent of, but complementary to, the previously identified PGRN lysosomal trafficking mediated by sortilin. Collectively, our results provide new understanding on PGRN trafficking and shed light on the molecular mechanisms behind FTLD and NCL caused by PGRN mutations. PMID- 26370504 TI - The formation of ordered nanoclusters controls cadherin anchoring to actin and cell-cell contact fluidity. PMID- 26370503 TI - alpha5beta1 integrin recycling promotes Arp2/3-independent cancer cell invasion via the formin FHOD3. AB - Invasive migration in 3D extracellular matrix (ECM) is crucial to cancer metastasis, yet little is known of the molecular mechanisms that drive reorganization of the cytoskeleton as cancer cells disseminate in vivo. 2D Rac driven lamellipodial migration is well understood, but how these features apply to 3D migration is not clear. We find that lamellipodia-like protrusions and retrograde actin flow are indeed observed in cells moving in 3D ECM. However, Rab coupling protein (RCP)-driven endocytic recycling of alpha5beta1 integrin enhances invasive migration of cancer cells into fibronectin-rich 3D ECM, driven by RhoA and filopodial spike-based protrusions, not lamellipodia. Furthermore, we show that actin spike protrusions are Arp2/3-independent. Dynamic actin spike assembly in cells invading in vitro and in vivo is regulated by Formin homology-2 domain containing 3 (FHOD3), which is activated by RhoA/ROCK, establishing a novel mechanism through which the RCP-alpha5beta1 pathway reprograms the actin cytoskeleton to promote invasive migration and local invasion in vivo. PMID- 26370506 TI - Use of biologics for psoriasis in Central and Eastern European countries. AB - OBJECTIVES: To evaluate the use of biological agents for the treatment of psoriasis and to explore country-specific differences within six Central and Eastern European (CEE) countries, namely Bulgaria, Croatia, the Czech Republic, Hungary, Poland and Romania. METHODS: A literature overview on the epidemiology and disease burden of psoriasis in CEE was conducted. The number of patients treated with biologics was obtained from patient registries, ministries of health, national professional societies and health insurance funds. Biological treatment rates were estimated by two different methods: (i) as a proportion of all psoriasis patients of a country (assuming a common prevalence of psoriasis 2%) and (ii) per 100,000 population. Moreover, we provide a detailed comparison of drug coverage policies and guidelines regulating the treatment with biologics in psoriasis. RESULTS: On average 0.25% of all psoriasis patients, or five psoriasis patients out of 100,000 inhabitants are treated with biologics embedding a 14.6-fold difference between the six countries. Bulgaria, Croatia and Poland lag behind the other three countries in the use of biologics. The significant differences among CEE countries cannot be explained by variations in prices of biologics, cost-effectiveness or budget impact of biologics. It seems that the time since coverage decision, the fewer number of covered biologics, the more restrictive criteria to be eligible for covered treatment in terms of baseline Psoriasis Area and Severity Index and Dermatology Life Quality Index scores, and the maximum duration of treatment allowed are responsible for the majority of the differences. CONCLUSIONS: There exists a disconnect between the European psoriasis treatment guidelines and the various CEE country-specific biologic coverage eligibilities. The cost of biologic therapy for psoriasis is not solely and directly responsible for the different use rates amongst the CEE countries. Psoriasis may not be perceived by all payers as a serious disease that can be successfully treated in a cost-effective manner. PMID- 26370505 TI - Integration of QUARK and I-TASSER for Ab Initio Protein Structure Prediction in CASP11. AB - We tested two pipelines developed for template-free protein structure prediction in the CASP11 experiment. First, the QUARK pipeline constructs structure models by reassembling fragments of continuously distributed lengths excised from unrelated proteins. Five free-modeling (FM) targets have the model successfully constructed by QUARK with a TM-score above 0.4, including the first model of T0837-D1, which has a TM-score = 0.736 and RMSD = 2.9 A to the native. Detailed analysis showed that the success is partly attributed to the high-resolution contact map prediction derived from fragment-based distance-profiles, which are mainly located between regular secondary structure elements and loops/turns and help guide the orientation of secondary structure assembly. In the Zhang-Server pipeline, weakly scoring threading templates are re-ordered by the structural similarity to the ab initio folding models, which are then reassembled by I TASSER based structure assembly simulations; 60% more domains with length up to 204 residues, compared to the QUARK pipeline, were successfully modeled by the I TASSER pipeline with a TM-score above 0.4. The robustness of the I-TASSER pipeline can stem from the composite fragment-assembly simulations that combine structures from both ab initio folding and threading template refinements. Despite the promising cases, challenges still exist in long-range beta-strand folding, domain parsing, and the uncertainty of secondary structure prediction; the latter of which was found to affect nearly all aspects of FM structure predictions, from fragment identification, target classification, structure assembly, to final model selection. Significant efforts are needed to solve these problems before real progress on FM could be made. Proteins 2016; 84(Suppl 1):76 86. (c) 2015 Wiley Periodicals, Inc. PMID- 26370507 TI - Regulation of EPS production in Lactobacillus casei LC2W through metabolic engineering. AB - Lactobacillus casei LC2W is an exopolysaccharide(EPS)-producing strain with probiotic effects. The low efficiency and unclear regulation mechanism of EPS biosynthesis have become main constraints for its application in food industry. To investigate the major rate-limiting factors of EPS biosynthesis and to improve its yield, metabolic engineering was applied to this strain. Eight relevant genes related to central metabolism, sugar-nucleotides supply, glycosyltransferase and cofactor engineering were cloned and overexpressed. The results suggested that nox, pfk, rfbB and galT genes were the largest contributors to EPS biosynthesis in this study, which elevated EPS yield by 46.0, 20, 17.4 and 19.6% respectively. Notably, under aerobic condition which was not a suitable condition for lactobacilli to grow in, recombinant strain LC-nox achieved the highest EPS yield of 263.7 mg l(-1) , which was increased by 75% compared to that of the starting strain. The oxygen stress was excluded since the phenomenon was not observed in the control strain under the same condition. Therefore, it was probably that higher NADH oxidase activity led to a decreased NADH availability and reduced lactate concentration, which resulted in the elevation of EPS yield. SIGNIFICANCE AND IMPACT OF THE STUDY: This study contributed to the understanding of EPS biosynthesis in Lact. casei through metabolic engineering and provided a starting point for introducing cofactor engineering into this strain. Overexpression of NADH oxidase was found to have a most significant effect on the EPS production. It is the first report that EPS could be accumulated to such a high level under aerobic condition in lactobacilli. Our results provided a novel strategy for the improvement of EPS production in lactic acid bacteria. PMID- 26370508 TI - Histone H3 Lysine 36 Trimethylation Is Established over the Xist Promoter by Antisense Tsix Transcription and Contributes to Repressing Xist Expression. AB - One of the two X chromosomes in female mammals is inactivated by the noncoding Xist RNA. In mice, X chromosome inactivation (XCI) is regulated by the antisense RNA Tsix, which represses Xist on the active X chromosome. In the absence of Tsix, PRC2-mediated histone H3 lysine 27 trimethylation (H3K27me3) is established over the Xist promoter. Simultaneous disruption of Tsix and PRC2 leads to derepression of Xist and in turn silencing of the single X chromosome in male embryonic stem cells. Here, we identified histone H3 lysine 36 trimethylation (H3K36me3) as a modification that is recruited by Tsix cotranscriptionally and extends over the Xist promoter. Reduction of H3K36me3 by expression of a mutated histone H3.3 with a substitution of methionine for lysine at position 36 causes a significant derepression of Xist. Moreover, depletion of the H3K36 methylase Setd2 leads to upregulation of Xist, suggesting H3K36me3 as a modification that contributes to the mechanism of Tsix function in regulating XCI. Furthermore, we found that reduction of H3K36me3 does not facilitate an increase in H3K27me3 over the Xist promoter, indicating that additional mechanisms exist by which Tsix blocks PRC2 recruitment to the Xist promoter. PMID- 26370509 TI - The New State of the Art: Cas9 for Gene Activation and Repression. AB - CRISPR-Cas9 technology has rapidly changed the landscape for how biologists and bioengineers study and manipulate the genome. Derived from the bacterial adaptive immune system, CRISPR-Cas9 has been coopted and repurposed for a variety of new functions, including the activation or repression of gene expression (termed CRISPRa or CRISPRi, respectively). This represents an exciting alternative to previously used repression or activation technologies such as RNA interference (RNAi) or the use of gene overexpression vectors. We have only just begun exploring the possibilities that CRISPR technology offers for gene regulation and the control of cell identity and behavior. In this review, we describe the recent advances of CRISPR-Cas9 technology for gene regulation and outline advantages and disadvantages of CRISPRa and CRISPRi (CRISPRa/i) relative to alternative technologies. PMID- 26370510 TI - Tristetraprolin Recruits Eukaryotic Initiation Factor 4E2 To Repress Translation of AU-Rich Element-Containing mRNAs. AB - Tristetraprolin (TTP) regulates the expression of AU-rich element-containing mRNAs through promoting the degradation and repressing the translation of target mRNA. While the mechanism for promoting target mRNA degradation has been extensively studied, the mechanism underlying translational repression is not well established. Here, we show that TTP recruits eukaryotic initiation factor 4E2 (eIF4E2) to repress target mRNA translation. TTP interacted with eIF4E2 but not with eIF4E. Overexpression of eIF4E2 enhanced TTP-mediated translational repression, and downregulation of endogenous eIF4E2 or overexpression of a truncation mutant of eIF4E2 impaired TTP-mediated translational repression. Overexpression of an eIF4E2 mutant that lost the cap-binding activity also impaired TTP's activity, suggesting that the cap-binding activity of eIF4E2 is important in TTP-mediated translational repression. We further show that TTP promoted eIF4E2 binding to target mRNA. These results imply that TTP recruits eIF4E2 to compete with eIF4E to repress the translation of target mRNA. This notion is supported by the finding that downregulation of endogenous eIF4E2 increased the production of tumor necrosis factor alpha (TNF-alpha) protein without affecting the mRNA levels in THP-1 cells. Collectively, these results uncover a novel mechanism by which TTP represses target mRNA translation. PMID- 26370511 TI - Global Transcriptome Analysis Reveals That Poly(ADP-Ribose) Polymerase 1 Regulates Gene Expression through EZH2. AB - Posttranslational modifications, such as poly(ADP-ribosyl)ation (PARylation), regulate chromatin-modifying enzymes, ultimately affecting gene expression. This study explores the role of poly(ADP-ribose) polymerase (PARP) on global gene expression in a lymphoblastoid B cell line. We found that inhibition of PARP catalytic activity with olaparib resulted in global gene deregulation, affecting approximately 11% of the genes expressed. Gene ontology analysis revealed that PARP could exert these effects through transcription factors and chromatin remodeling enzymes, including the polycomb repressive complex 2 (PRC2) member EZH2. EZH2 mediates the trimethylation of histone H3 at lysine 27 (H3K27me3), a modification associated with chromatin compaction and gene silencing. Both pharmacological inhibition of PARP and knockdown of PARP1 induced the expression of EZH2, which resulted in increased global H3K27me3. Chromatin immunoprecipitation confirmed that PARP1 inhibition led to H3K27me3 deposition at EZH2 target genes, which resulted in gene silencing. Moreover, increased EZH2 expression is attributed to the loss of the occupancy of the transcription repressor E2F4 at the EZH2 promoter following PARP inhibition. Together, these data show that PARP plays an important role in global gene regulation and identifies for the first time a direct role of PARP1 in regulating the expression and function of EZH2. PMID- 26370512 TI - High CO2 Leads to Na,K-ATPase Endocytosis via c-Jun Amino-Terminal Kinase-Induced LMO7b Phosphorylation. AB - The c-Jun amino-terminal kinase (JNK) plays a role in inflammation, proliferation, apoptosis, and cell adhesion and cell migration by phosphorylating paxillin and beta-catenin. JNK phosphorylation downstream of AMP-activated protein kinase (AMPK) activation is required for high CO2 (hypercapnia)-induced Na,K-ATPase endocytosis in alveolar epithelial cells. Here, we provide evidence that during hypercapnia, JNK promotes the phosphorylation of LMO7b, a scaffolding protein, in vitro and in intact cells. LMO7b phosphorylation was blocked by exposing the cells to the JNK inhibitor SP600125 and by infecting cells with dominant-negative JNK or AMPK adenovirus. The knockdown of the endogenous LMO7b or overexpression of mutated LMO7b with alanine substitutions of five potential JNK phosphorylation sites (LMO7b-5SA) or only Ser-1295 rescued both LMO7b phosphorylation and the hypercapnia-induced Na,K-ATPase endocytosis. Moreover, high CO2 promoted the colocalization and interaction of LMO7b and the Na,K-ATPase alpha1 subunit at the plasma membrane, which were prevented by SP600125 or by transfecting cells with LMO7b-5SA. Collectively, our data suggest that hypercapnia leads to JNK-induced LMO7b phosphorylation at Ser-1295, which facilitates the interaction of LMO7b with Na,K-ATPase at the plasma membrane promoting the endocytosis of Na,K-ATPase in alveolar epithelial cells. PMID- 26370513 TI - Identification by Random Mutagenesis of Functional Domains in KREPB5 That Differentially Affect RNA Editing between Life Cycle Stages of Trypanosoma brucei. AB - KREPB5 is an essential component of ~ 20S editosomes in Trypanosoma brucei which contains a degenerate, noncatalytic RNase III domain. To explore the function of this protein, we used a novel approach to make and screen numerous conditional null T. brucei bloodstream form cell lines that express randomly mutagenized KREPB5 alleles. We identified nine single amino acid substitutions that could not complement the conditional loss of wild-type KREPB5. Seven of these were within the RNase III domain, and two were in the C-terminal region that has no homology to known motifs. Exclusive expression of these mutated KREPB5 alleles in the absence of wild-type allele expression resulted in growth inhibition, the loss of ~ 20S editosomes, and inhibition of RNA editing in BF cells. Eight of these mutations were lethal in bloodstream form parasites but not in procyclic-form parasites, showing that multiple domains function in a life cycle-dependent manner. Amino acid changes at a substantial number of positions, including up to 7 per allele, allowed complementation and thus did not block KREPB5 function. Hence, the degenerate RNase III domain and a newly identified domain are critical for KREPB5 function and have differential effects between the life cycle stages of T. brucei that differentially edit mRNAs. PMID- 26370514 TI - A nitrogen-vacancy spin based molecular structure microscope using multiplexed projection reconstruction. AB - Methods and techniques to measure and image beyond the state-of-the-art have always been influential in propelling basic science and technology. Because current technologies are venturing into nanoscopic and molecular-scale fabrication, atomic-scale measurement techniques are inevitable. One such emerging sensing method uses the spins associated with nitrogen-vacancy (NV) defects in diamond. The uniqueness of this NV sensor is its atomic size and ability to perform precision sensing under ambient conditions conveniently using light and microwaves (MW). These advantages have unique applications in nanoscale sensing and imaging of magnetic fields from nuclear spins in single biomolecules. During the last few years, several encouraging results have emerged towards the realization of an NV spin-based molecular structure microscope. Here, we present a projection-reconstruction method that retrieves the three-dimensional structure of a single molecule from the nuclear spin noise signatures. We validate this method using numerical simulations and reconstruct the structure of a molecular phantom beta-cyclodextrin, revealing the characteristic toroidal shape. PMID- 26370515 TI - REVascularization with paclitaxEL-coated balloon angioplasty versus drug-eluting stenting in acute myocardial infarcTION-A randomized controlled trial: Rationale and design of the REVELATION trial. AB - AIM: In primary percutaneous coronary intervention (PPCI) for ST-elevation myocardial infarction (STEMI), stenting has proved to reduce the need for repeat revascularization compared with balloon angioplasty alone. The incidence of cardiac death or recurrent myocardial infarction, though, is not reduced by stenting. This is in part attributable to stent-related complications like stent thrombosis which may occur even years after implantation. A strategy of drug coated balloon (DCB) angioplasty without stenting would abolish the potential disadvantages of stent implantation while reducing the probability of restenosis observed in plain old balloon angioplasty. Our aim is to evaluate the efficacy and safety of a DCB only strategy versus drug-eluting stents (DES) in PPCI for STEMI. STUDY DESIGN: The REVELATION trial is a prospective, single center, randomized study, in which 120 patients presenting with STEMI will be allocated to treatment with a DCB versus DES. Appertaining to the established prognostic value of fractional flow reserve (FFR) rather than angiographic lesion severity, the functional assessment of the infarct-related lesion by FFR at 9 months after initial treatment is the primary end point. Assuming an FFR value of 0.90 after stenting and an increased risk of adverse events if post-PCI FFR <0.85, we decided to accept an FFR value of >=0.85 after DCB only at follow-up as noninferiority margin. Secondary end points include major adverse cardiac events up to 5-year follow-up. CONCLUSION: Our trial will address the efficacy and safety of DCB angioplasty versus DES in the setting of PPCI for STEMI. The REVELATION trial will introduce the recognized prognostic significance of physiologic assessment of the infarct-related lesion by FFR at 9 months follow-up as primary end point. (c) 2015 Wiley Periodicals, Inc. PMID- 26370516 TI - Rest and the associated benefits in restorative sleep: a concept analysis. AB - AIM: To report an analysis of the concept of rest. BACKGROUND: Consistency in the literature to describe the concept and use of rest is limited. Concept analysis may be advantageous in rendering an operational definition in the health care setting. This analysis is important to examine the concept of rest for structure and function to promote an understanding of the phenomenon. Rest is a vital component of restorative sleep which has implications for physical, mental and spiritual well-being. DESIGN: Concept analysis. DATA SOURCES: A literature search was conducted in the following databases: PubMed, CINAHL, Medline, ProQuest and an online Internet search with the majority of articles published between 1995 2015. METHODS: This concept analysis was implemented using the eight step approach developed by Walker and Avant. RESULTS: In health care, rest incorporates the cessation of activity used to promote physical and mental health. Defining attributes of rest include a pathway to calm, inner tranquillity and mental health; base of support; and stillness. Antecedents for rest are time, suitable environment and willingness. Resulting consequences include renewed physical energy, mental clarity and improved health. CONCLUSION: Rest is a concept that is used frequently in the discipline of nursing but also in various other disciplines. Rest is a basic necessity for restorative sleep to enhance well-being through the restoration of the body, mind and spirit. Defining the concept of rest in the practice of patient care is necessary for consistent use of the term in the development of holistic, patient-centred therapies. PMID- 26370517 TI - Challenges and Opportunities for Electrochemical Processes as Next-Generation Technologies for the Treatment of Contaminated Water. AB - Electrochemical processes have been extensively investigated for the removal of a range of organic and inorganic contaminants. The great majority of these studies were conducted using nitrate-, perchlorate-, sulfate-, and chloride-based electrolyte solutions. In actual treatment applications, organic and inorganic constituents may have substantial effects on the performance of electrochemical treatment. In particular, the outcome of electrochemical oxidation will depend on the concentration of chloride and bromide. Formation of chlorate, perchlorate, chlorinated, and brominated organics may compromise the quality of the treated effluent. A critical review of recent research identifies future opportunities and research needed to overcome major challenges that currently limit the application of electrochemical water treatment systems for industrial and municipal water and wastewater treatment. Given the increasing interest in decentralized wastewater treatment, applications of electrolytic systems for treatment of domestic wastewater, greywater, and source-separated urine are also included. To support future adoption of electrochemical treatment, new approaches are needed to minimize the formation of toxic byproducts and the loss of efficiency caused by mass transfer limitations and undesired side reactions. Prior to realizing these improvements, recognition of the situations where these limitations pose potential health risks is a necessary step in the design and operation of electrochemical treatment systems. PMID- 26370518 TI - V1 neurons respond differently to object motion versus motion from eye movements. AB - How does the visual system differentiate self-generated motion from motion in the external world? Humans can discern object motion from identical retinal image displacements induced by eye movements, but the brain mechanisms underlying this ability are unknown. Here we exploit the frequent production of microsaccades during ocular fixation in the primate to compare primary visual cortical responses to self-generated motion (real microsaccades) versus motion in the external world (object motion mimicking microsaccades). Real and simulated microsaccades were randomly interleaved in the same viewing condition, thereby producing equivalent oculomotor and behavioural engagement. Our results show that real microsaccades generate biphasic neural responses, consisting of a rapid increase in the firing rate followed by a slow and smaller-amplitude suppression that drops below baseline. Simulated microsaccades generate solely excitatory responses. These findings indicate that V1 neurons can respond differently to internally and externally generated motion, and expand V1's potential role in information processing and visual stability during eye movements. PMID- 26370519 TI - Large difference in carbon emission - burial balances between boreal and arctic lakes. AB - Lakes play an important role in the global carbon (C) cycle by burying C in sediments and emitting CO2 and CH4 to the atmosphere. The strengths and control of these fundamentally different pathways are therefore of interest when assessing the continental C balance and its response to environmental change. In this study, based on new high-resolution estimates in combination with literature data, we show that annual emission:burial ratios are generally ten times higher in boreal compared to subarctic - arctic lakes. These results suggest major differences in lake C cycling between biomes, as lakes in warmer boreal regions emit more and store relatively less C than lakes in colder arctic regions. Such effects are of major importance for understanding climatic feedbacks on the continental C sink - source function at high latitudes. If predictions of global warming and northward expansion of the boreal biome are correct, it is likely that increasing C emissions from high latitude lakes will partly counteract the presumed increasing terrestrial C sink capacity at high latitudes. PMID- 26370520 TI - A randomized trial of direct pulp capping in primary molars using MTA compared to 3Mixtatin: a novel pulp capping biomaterial. AB - OBJECTIVE: This study aimed to examine the efficacy of 3Mixtatin (a combination of simvastatin and 3Mix antibiotic) as a novel pulp capping biomaterial in DPC of human primary molars. METHODS: In this randomized clinical trial, 160 primary molars from 83 healthy children aged 3-6 years were randomly allocated into four groups. Small traumatic non-caries pulpal exposures were treated by DPC using simvastatin, 3Mix, 3Mixtatin, or MTA. Capping materials were covered with hard setting zinc oxide eugenol (ZOE) cement, and then, teeth were restored with amalgam. Clinical and radiographic examinations were conducted at 2, 6, and 12 months after treatment. The data were compared using chi-square test at a significance level of 0.05. RESULTS: One hundred and twenty-nine teeth were available for follow-up study. By the end of 12 months, the overall success rates were 93.8% in MTA, 91.9% in 3Mixtatin, 62.5% in 3Mix, and 57.1% in simvastatingroups. No statistically significant difference was found between the outcomes of MTA and 3Mixtatin groups (P > 0.05). 3Mixtatin had statistically superior results compared to 3Mix and simvastatin (P < 0.01). CONCLUSION: Radiographic and clinical outcomes in 3Mixtatin group could suggest it as an acceptable alternative in DPC of primary molar teeth. PMID- 26370522 TI - Usefulness of silkworm as a model animal for understanding the molecular mechanisms of fungal pathogenicity. AB - Candida albicans, Candida tropicalis, Candida grabrata, and Cryptococcus neoformans are causative pathogens of opportunistic diseases in immunocompromised human patients. Silkworms are killed by injection of these pathogenic fungi into their hemolymph. In this paper, we describe recent results by our laboratory and other researchers using gene-deficient strains of these pathogenic fungi. The silkworm is considered to be a useful model animal for understanding the pathogenicity of these fungi. Silkworms are also beneficial for evaluating therapeutically active anti-fungal reagents. PMID- 26370521 TI - Complete mitochondrial genome of the medicinal fungus Ophiocordyceps sinensis. AB - As part of a genome sequencing project for Ophiocordyceps sinensis, strain 1229, a complete mitochondrial (mt) genome was assembled as a single circular dsDNA of 157,510 bp, one of the largest reported for fungi. Conserved genes including the large and small rRNA subunits, 27 tRNA and 15 protein-coding genes, were identified. In addition, 58 non-conserved open reading frames (ncORFs) in the intergenic and intronic regions were also identified. Transcription analyses using RNA-Seq validated the expression of most conserved genes and ncORFs. Fifty two introns (groups I and II) were found within conserved genes, accounting for 68.5% of the genome. Thirty-two homing endonucleases (HEs) with motif patterns LAGLIDADG (21) and GIY-YIG (11) were identified in group I introns. The ncORFs found in group II introns mostly encoded reverse transcriptases (RTs). As in other hypocrealean fungi, gene contents and order were found to be conserved in the mt genome of O. sinensis, but the genome size was enlarged by longer intergenic regions and numerous introns. Intergenic and intronic regions were composed of abundant repetitive sequences usually associated with mobile elements. It is likely that intronic ncORFs, which encode RTs and HEs, may have contributed to the enlarged mt genome of O. sinensis. PMID- 26370523 TI - Oesophageal squamous cell carcinoma (ESCC): Advances through omics technologies, towards ESCC salivaomics. AB - Oesophageal Squamous Cell Carcinoma (ESCC) is one of the two main subtypes of oesophageal cancer, affecting mainly populations in Asia. Though there have been great efforts to develop methods for a better prognosis, there is still a limitation in the staging of this affection. As a result, ESCC is detected at advances stages, when the interventions on the patient do not have such a positive outcome, leading in many cases to recurrence and to a very low 5-year survival rate, causing high mortality. A way to decrease the number of deaths is the use of biomarkers that can trace the advance of the disease at early stages, when surgical or chemotherapeutic methodologies would have a greater effect on the evolution of the subject. The new high throughput omics technologies offer an unprecedented chance to screen for thousands of molecules at the same time, from which a new set of biomarkers could be developed. One of the most convenient types of samples is saliva, an accessible body fluid that has the advantage of being non-invasive for the patient, being easy to store or to process. This review will focus on the current status of the new omics technologies regarding salivaomics in ESCC, or when not evaluated yet, the achievements in related diseases. PMID- 26370524 TI - Evaluation of antithrombotic effect: Importance of testing components and methodologies. AB - The beneficial antithrombotic effect of some dietary components may offer the most promising approach of prevention of cardiovascular diseases and arterial thrombosis. The major stumbling block in finding effective dietary components is the lack of physiologically relevant techniques which can detect potential antithrombotic effect in humans. The presently used platelet function and coagulation tests do not allow the assessment of global thrombotic status and their value in screening dietary components for antithrombotic effect is questionable. Most of these in vitro tests ignore the effect of flow and shear stress, thrombin generation and vascular endothelium, the major contributors to arterial thrombogenesis in humans. As a gold standard, we employed the helium neon (He-Ne) laser-induced thrombosis test in murine carotid artery and mesenteric microvessels, as the pathomechanism of this test closely reflects arterial thrombogenesis in humans. Results obtained with laser thrombosis test were compared with various shear-induced in vitro platelet function tests which use native blood (Haemostatometry, Thrombotic Status Analyser, Global Thrombosis Test-GTT). Contribution of vascular endothelium to thrombogenesis was assessed by measuring flow-mediated vasodilation (FMV) in vivo. The combination of the two shear-induced ex vivo thrombosis tests (Haemostatometry and GTT) with FMV correlated most closely with the laser-thrombosis test. Our findings suggest that combining the commercially available point-of-care GTT with the FMV test could provide a better assessment of the overall thrombotic status than either of the two tests alone. PMID- 26370525 TI - An examination on the modern significance of "Yakushokudougen" in transferring to organic agriculture. AB - This study attempts to identify whether and why the difference in corruption progress exists between organic and conventional farm products by conducting two corruption experiments of farm products and separation experiment of bacteria, as well as farmer survey. The results of corruption experiments for Wenzhou mandarin oranges (Citrus unshiu) and polished rice showed that conventional farm products demonstrated fast-growing corruption with strong unpleasant smell distinctively different from organic farm products. The separation experiment of bacteria indicated a high possibility of fungus appearance in organic farm products and coccus or bacillus appearance in conventional farm products, which are significantly consistent with the results of two corruption experiments and the fact that organic farmers are strongly conscious of the use of fermented organic fertilizers with effective microorganism in their cultivation. These results offer empirical evidences for supporting the development of organic agriculture and the consumption expansion of organic farm products, but further works are necessary. PMID- 26370526 TI - Association between maternal diabetes mellitus and the risk of congenital malformations: A meta-analysis of cohort studies. AB - Increasing studies suggest that gestational diabetes mellitus (GDM) and pre gestational diabetes mellitus (PGDM) may be associated with an increased risk of major congenital malformations (MCM) in the offspring. To determine whether GDM or PGDM is associated with an increased risk of congenital malformations, we performed a meta-analysis of cohort studies. We systematically searched the PubMed, Web of Science and Cochrane Library (from January, 1990 to October, 2014) and reviewed the reference lists of included papers to search for additional studies. Meta-analysis tools were used to summarize results. Summary relative risks (RRs) with 95% confidence intervals (CIs) were calculated with random effects models or fixed-effects models. Study quality was assessed using the Newcastle-Ottawa scale. A total of 21 cohort studies were included in the meta analysis. Analysis of all studies showed that both PGDM and GDM were associated with an increased risk of MCM (RR=2.44, 95% CI=1.92-3.10, I2=78.3%, p=0.342; RR=1.11, 95% CI=1.11-1.27, I2=9.9%, p<0.001, respectively). There is a slightly higher risk of major congenital malformations in women with GDM than in the reference group. However, this risk is much lower than in women with PGDM. Further large-scale prospective cohort studies are needed to test the effect of PGDM and GDM on specific congenital malformations risk. PMID- 26370527 TI - Combination of immunoprecipitation (IP)-ATP_Glo kinase assay and melanogenesis for the assessment of potent and safe PAK1-blockers in cell culture. AB - Cucurbitacin I (CBI) is a triterpene from a bitter melon called Goya grown in Okinawa, Japan, and directly inhibits both the Tyr-kinase JAK2 and the G protein RAC, leading to the inactivation of PAK1 (RAC/CDC42-activated kinase 1). Bio 30, a propolis produced in New Zealand, contains CAPE (caffeic acid phenethyl ester) as the major anti-cancer ingredient which directly down-regulates RAC, leading to the inactivation of PAK1. Since PAK1 is essential for the growth of RAS cancer cells such as A549 cell line which carry an oncogenic K-RAS mutant, and the melanogenesis in skin cells, here using these PAK1-blockers as model compounds, we introduce a new approach to the quick assessment of PAK1-blockers in cell culture. First, combining the immuno-precipitation (IP) of PAK1 from cell lysate and the in vitro ATP_Glo kinase assay kit (called "Macaroni-Western" assay), we confirmed that both CBI and Bio 30 inactivate PAK1 in A549 lung cancer cells in 24 h, and inhibit their PAK1-dependent growth in 72 h. Furthermore, we verified that CBI inhibits the PAK1/PAK4-dependent melanogenesis in melanoma cells by far more than 50%, while Bio 30 inhibits the melanogenesis only by 50%, with only a merginal effect on their growth per se. Since the "Macaroni-Western" kinase assay and melanogenesis are both rather simple and quick, the combination of these two cell culture assays would be highly useful for selecting both "potent" (highly cell-permeable) and "safe" (non-toxic) natural or synthetic PAK1-blockers. PMID- 26370528 TI - Evaluation of stroke volume variation and pulse pressure variation as predictors of fluid responsiveness in patients undergoing protective one-lung ventilation. AB - In order to investigate whether the hemodynamic indices, including stroke volume variation (SVV) and pulse pressure variation (PPV) could predict fluid responsiveness in patients undergoing protective one-lung ventilation. 60 patients scheduled for a combined thoracoscopic and laparoscopic esophagectomy were enrolled and randomized into two groups. The patients in the protective group (Group P) were ventilated with a tidal volume of 6 mL/kg, an inspired oxygen fraction (FiO2) of 80%, and a positive end expiratory pressure (PEEP) of 5 cm H2O. Patients in the conventional group (Group C) were ventilated with a tidal volume of 8 mL/kg and a FiO2 of 100%. Dynamic variables were collected before and after fluid loading (7 mL/kg hydroxyethyl starch 6%, 0.4 mL/kg/min). Patients whose stroke volume index (SVI) increased by more than 15% were defined as responders. Data collected from 45 patients were finally analyzed. Twelve of 24 patients in Group P and 10 of 21 patients in Group C were responders. SVV and PPV significantly changed after the fluid loading. The receive operating characteristic (ROC) analysis showed that the thresholds for SVV and PPV to discriminate responders were 8.5% for each, with a sensitivity of 66.7% (SVV) and 75% (PPV) and a specificity of 50% (SVV) and 83.3% (PPV) in Group P. However, the thresholds for SVV and PPV were 8.5% and 7.5% with a sensitivity of 80% (SVV) and 90% (PPV) and a specificity of 70% (SVV) and 80% (PPV) in Group C. We found SVV and PPV could predict fluid responsiveness in protective one-lung ventilation, but the accuracy and ability of SVV and PPV were weak compared with the role they played in a conventional ventilation strategy. PMID- 26370529 TI - Fabrication of porous ethyl cellulose microspheres based on the acetone-glycerin water ternary system: Controlling porosity via the solvent-removal mode. AB - Porous ethyl cellulose (EC) microspheres were prepared from the acetone-glycerin water ternary system using an oil/water (O/W)-type emulsion solvent extraction method. The O/ W type emulsion was prepared using acetone dissolved ethyl cellulose as an oil phase and aqueous glycerin as a water phase. The effects of the different solvent extraction modes on the porosity of the microspheres were investigated. The specific surface area of the porous EC microspheres was estimated by the gas adsorption method. When the solvent was extracted rapidly by mixing the emulsion with water instantaneously, porous EC microspheres with a maximum specific surface area of 40.7+/-2.1 m2/g were obtained. On the other hand, when water was added gradually to the emulsion, the specific surface area of the fabricated microspheres decreased rapidly with an increase in the infusion period, with the area being 25-45% of the maximum value. The results of an analysis of the ternary phase diagram of the system suggested that the penetration of water and glycerin from the continuous phase to the dispersed phase before solidification affected the porosity of the fabricated EC microspheres. PMID- 26370530 TI - Comparison between follicular stimulation and luteal stimulation protocols with clomiphene and HMG in women with poor ovarian response. AB - This retrospective study is to compare the follicular mild stimulation and luteal simulation protocols for poor responders undergoing in vitro fertilization (IVF). A total of 131 women were diagnosed as poor responders. Thirty-three women started ovarian stimulation in early-luteal phase and 98 women started in early follicular phase with 100 mg/d clomiphene citrate and 75-150 IU/d HMG. There were more oocytes retrieved (2.8 +/- 2.0 versus 2.0 +/- 1.2, p < 0.05), more available embryos (1.8 +/- 1.4 versus 1.3 +/- 1.1, p < 0.05) and top-quality embryos (0.9 +/- 0.9 versus 0.4 +/- 0.6, p < 0.05), and reduced cycle cancellation rate (12.1% versus 30.6%, p < 0.05) in luteal group than in follicular group. The clinical pregnancy (17.7%, 20.0% and 41.2%) and live-birth rates (10.78%, 20.0% and 29.4%) after transferring embryos obtained from luteal, follicular and mixed stages were comparable (p > 0.05). For poor responders, luteal phase stimulation could be an option because of increasing the chance to obtain competent embryos and reducing the cycle cancellation rate. PMID- 26370531 TI - Speckle disturbance limit in laser-based cinema projection systems. AB - In a multi-disciplinary effort, we investigate the level of speckle that can be tolerated in a laser cinema projector based on a quality of experience experiment with movie clips shown to a test audience in a real-life movie theatre setting. We identify a speckle disturbance threshold by statistically analyzing the observers' responses for different values of the amount of speckle, which was monitored using a well-defined speckle measurement method. The analysis shows that the speckle perception of a human observer is not only dependent on the objectively measured amount of speckle, but it is also strongly influenced by the image content. The speckle disturbance limit for movies turns out to be substantially larger than that for still images, and hence is easier to attain. PMID- 26370532 TI - Detection of antibiotic resistance in probiotics of dietary supplements. AB - BACKGROUND: Probiotics are live microorganisms that confer nutrition- and health promoting benefits if consumed in adequate amounts. Concomitant with the demand for natural approaches to maintaining health is an increase in inclusion of probiotics in food and health products. Since probiotic bacteria act as reservoir for antibiotic resistant determinants, the transfer of these genes to pathogens sharing the same intestinal habitat is thus conceivable considering the fact that dietary supplements contain high amounts of often heterogeneous populations of probiotics. Such events can confer pathogens protection against commonly-used drugs. Despite numerous reports of antibiotic resistant probiotics in food and biological sources, the antibiogram of probiotics from dietary supplements remained elusive. FINDINGS: Here, we screened five commercially available dietary supplements for resistance towards antibiotics of different classes. Probiotics of all batches of products were resistant towards vancomycin while batch dependent resistance towards streptomycin, aztreonam, gentamycin and/or ciprofloxacin antibiotics was detected for probiotics of brands Bi and Bn, Bg, and L. Isolates of brand Cn was also resistant towards gentamycin, streptomycin and ciprofloxacin antibiotics. Additionally, we also report a discrepancy between the enumerated viable bacteria amounts and the claims of the manufacturers. CONCLUSIONS: This short report has highlighted the present of antibiotic resistance in probiotic bacteria from dietary supplements and therefore serves as a platform for further screenings and for in-depth characterization of the resistant determinants and the molecular machinery that confers the resistance. PMID- 26370533 TI - Complete mitochondrial genome of Schizopygopsis chengi chengi (Cyprinidae, Schizothoracinae, Schizopygopsis). AB - The complete mitochondrial DNA sequence of Schizopygopsis chengi chengi collected from the Dadu River was determined in this study. The complete mitochondrial genome of S. chengi chengi was a circular molecule of 16 688 bp in size, and all genes showed the typical gene arrangement conforming to the vertebrate consensus. Twelve protein-coding genes (except ND6) of S. chengi chengi and other 22 Schizothoracinae species from two genera were used for phylogenetic analysis by Bayesian inference and maximum likelihood methods. The topology confirmed the close genetic relationship between S. chengi chengi and S. chengi baoxinggensis. PMID- 26370534 TI - Anti-epileptic drug changes and quality of life in the community. AB - OBJECTIVE: Changes in anti-epileptic drug (AED) regimens may indicate unsatisfactory treatment results such as insufficient seizure control or adverse effects. This inference underlies epilepsy management and research, yet current studies often do not account for AED changes. We assessed AED change patterns and their association with quality of life (QoL), as main outcome measure, in a community-based setting. METHODS: We assessed a cohort of 248 people with epilepsy identified from community pharmacy records from whom we retrieved AED dispensing history. We assessed all changes in AED use during the 2 years prior to the index date and current QoL using the validated Dutch QOLIE-31 questionnaire. RESULTS: Thirty-one per cent had at least one AED change during the study period, either in drug type or dose. People who changed showed significantly lower QoL (QOLIE score 73 vs 79), especially those who intensified their treatment. Each additional change was associated with a further reduction of 4.9 points in QoL score. CONCLUSIONS: AED changes are common practice, even in people with long-standing epilepsy. Frequent changes, as objective measure of epilepsy severity, are associated with a progressively lower QoL. Changes, even in dose, should be monitored in daily clinical practice and used as a red flag that may require adjustments in epilepsy management. This may include earlier referral to a specialized centre for a more thorough evaluation or counselling. AED changes can also be used as an outcome marker in epilepsy research as a proxy of QoL for better translation of drug-efficacy results to general practice. PMID- 26370535 TI - Childhood type 1 diabetes may increase the risk of atopic dermatitis. AB - BACKGROUND: Epidemiological investigations have examined the association between type 1 diabetes mellitus (T1DM) and atopic disease, but have obtained conflicting results. OBJECTIVES: To analyse the association between T1DM and atopic dermatitis (AD) in a population-based, retrospective cohort study that investigated the hypothesis that childhood T1DM is a risk factor for subsequent AD. METHODS: From claims data of the National Health Insurance programme of Taiwan, we identified 3386 patients with T1DM newly diagnosed from 1998 to 2011 and 12 725 randomly selected controls without T1DM. These were frequency matched by age, sex and year of diagnosis. Both cohorts were followed up until the end of 2011 to evaluate the AD risk. We used Cox proportional hazards regression models to analyse the risk of AD. RESULTS: The overall incidence rate of AD was 1.40 fold (significantly) higher in the T1DM cohort than in the non-T1DM cohort (3.31 vs. 2.35 per 1000 person years). After adjustment for potential risk factors, the overall risk of AD remained higher in the T1DM cohort [adjusted hazard ratio (HR) 1.76, 95% confidence interval (CI) 1.29-2.39] than in those without T1DM. Compared with the non-T1DM cohort, the patients with T1DM with more emergency room visits (adjusted HR 30.1, 95% CI 18.7-48.5) or hospitalizations (adjusted HR 70.3, 95% CI 45.6-114.5) had a higher risk of subsequent AD. CONCLUSIONS: This nationwide, retrospective cohort study demonstrates that childhood T1DM may increase the risk of AD. PMID- 26370536 TI - Computer-Based Visualization System for the Study of Deep Brain Structures Involved in Parkinson's Disease. AB - Parkinson's Disease is characterized by alterations in deep brain structures and pathways involved in movement control. However, the understanding of neuroanatomy and spatial relationships of deep brain structures remains a challenge for medical students. Recent developments in information technology may help provide new instructional material that addresses this problem. This paper aims to develop an interactive and digital tool to enhance the study of the anatomical and functional neurological basis involved in Parkinson's Disease. This tool allows the organization and exploration of complex neuroanatomical contents related with Parkinson's Disease in an attractive and interactive way. Educational implications of this tool are analyzed. PMID- 26370537 TI - Nonvolatile Ferroelectric Memory Circuit Using Black Phosphorus Nanosheet-Based Field-Effect Transistors with P(VDF-TrFE) Polymer. AB - Two-dimensional van der Waals (2D vdWs) materials are a class of new materials that can provide important resources for future electronics and materials sciences due to their unique physical properties. Among 2D vdWs materials, black phosphorus (BP) has exhibited significant potential for use in electronic and optoelectronic applications because of its allotropic properties, high mobility, and direct and narrow band gap. Here, we demonstrate a few-layered BP-based nonvolatile memory transistor with a poly(vinylidenefluoride-trifluoroethylene) (P(VDF-TrFE)) ferroelectric top gate insulator. Experiments showed that our BP based ferroelectric transistors operate satisfactorily at room temperature in ambient air and exhibit a clear memory window. Unlike conventional ambipolar BP transistors, our ferroelectric transistors showed only p-type characteristics due to the carbon-fluorine (C-F) dipole effect of the P(VDF-TrFE) layer, as well as the highest linear mobility value of 1159 cm(2) V(-1) s(-1) with a 10(3) on/off current ratio. For more advanced memory applications beyond unit memory devices, we implemented two memory inverter circuits, a resistive-load inverter circuit and a complementary inverter circuit, combined with an n-type molybdenum disulfide (MoS2) nanosheet. Our memory inverter circuits displayed a clear memory window of 15 V and memory output voltage efficiency of 95%. PMID- 26370539 TI - Organic Anion Transporter 1 Is Inhibited by Multiple Mechanisms and Shows a Transport Mode Independent of Exchange. AB - The mechanism by which drugs inhibit organic anion transporter 1 (OAT1) was examined. OAT1 was stably expressed in Chinese hamster ovary (CHO) cells, and para-aminohippurate (PAH) and 6-carboxyfluorescein were the substrates. Most compounds (10 of 14) inhibited competitively, increasing the Michaelis constant (Km) without affecting the maximal transport rate (Jmax). Others were mixed-type (lowering Jmax and increasing Km) or noncompetitive (lowering Jmax only) inhibitors. The interaction of a noncompetitive inhibitor (telmisartan) with OAT1 was examined further. Binding of telmisartan to OAT1 was observed, but translocation was not. Telmisartan did not alter the plasma membrane expression of OAT1, indicating that it lowers Jmax by reducing the turnover number. PAH transport after telmisartan treatment and its washout recovered faster in the presence of 10% fetal bovine serum in the washout buffer, indicating that binding of telmisartan to OAT1 and its inhibitory effect are reversible. Together, these data suggest that telmisartan binds reversibly to a site distinct from substrate and stabilizes the transporter in a conformation unfavorable for translocation. In the absence of an exchangeable extracellular substrate, PAH efflux from CHO OAT1 cells was relatively rapid. Telmisartan slowed PAH efflux, suggesting that some transporter-mediated efflux occurs independent of exchange. Although drug drug interaction predictions at OAT1 assume competitive inhibition, these data show that OAT1 can be inhibited by other mechanisms, which could influence the accuracy of drug-drug interaction predictions at the transporter. Telmisartan was useful for examining how a noncompetitive inhibitor can alter OAT1 transport activity and for uncovering a transport mode independent of exchange. PMID- 26370540 TI - Stress, antioxidant defence and mucosal immune responses of the large yellow croaker Pseudosciaena crocea challenged with Cryptocaryon irritans. AB - To clarify the effects of a Cryptocaryon irritans infection on the stress, antioxidant and mucosal immune response of the large yellow croaker Pseudosciaena crocea, this study utilized C. irritans at dose of 12,000 (group I); 24,000 (group II); and 36,000 (group III) theronts/fish to infect large yellow croaker weighing 100 +/- 10 g. The food intake, survival and relative infection intensity (RII); levels of reactive oxygen species (ROS), malondialdehyde (MDA) and vitamin C (VC), activities of super oxide dismutase (SOD) and catalase (CAT) in liver; variation patterns of lysozyme (LZM), alkaline phosphatase (AKP), complement component 3 (C3) and immunoglobulin M (IgM) levels in the body surface mucus at different time points after infection were compared. These results showed that with the increase of the infection dose and the passage of time, the food intake and survival of the fish gradually decreased. The final survival of the control group (0 theronts/fish), group I, group II, and group III was 100, 100, 96.67 +/- 5.77, and 48.33 +/- 7.64. Group I, II, and III stopped feeding respectively on the third, third and second days after infection. RII increased significantly with increased infection dose. The RII of the control group, group I, group II, and group III was 0, 0.73 +/- 0.06, 1.30 +/- 0.26, and 1.84 +/- 0.02. With the infection dose increased, ROS contents showed an overall upward trend; MDA contents of the group I, group II and group III did not show significant changes at any timepoint compared with the control group; Activities of SOD and CAT and the overall VC levels in the liver of P. crocea dropped; LZM activity showed an overall upward trend; AKP activity increased first then dropped at each timepoint with its highest level appearing at group II; Complement C3 and IgM levels in body surface mucus were significantly increased. In conclusion, P. crocea has a strong ability to resist oxidative stress caused by the infection of C. irritans. The body surface mucus of P. crocea contains high levels of immune factors, which presented a rapid and significant response to the infection of C. irritans. PMID- 26370541 TI - Identification and characterization of IKKepsilon gene from grass carp Ctenopharyngodon idella. AB - IKKepsilon is an IKK-related kinase implicated in antiviral immune response in higher vertebrates. To elucidate the function of IKKepsilon in teleost fish, grass carp IKKepsilon (gcIKKepsilon) has been cloned and characterized in this paper. The full-length cDNA of gcIKKepsilon is composed of 2529 nucleotides and encodes a polypeptide of 723 amino acids. The mRNA transcription of gcIKKepsilon was constitutively detected in all the selected tissues and the gcIKKepsilon mRNA level increased at 36 h after GCRV infection. Western blot data of both HEK293T cells and EPC cells demonstrated that gcIKKepsilon was around 80 KDa; and immunofluorescence staining data of both NIH3T3 cells and EPC cells determined gcIKKepsilon was a cytosolic protein. The mRNA level of gcIKKepsilon in CIK cells was increased more than 150 times right after poly(I:C) treatment and PMA treatment triggered gcIKKepsilon mRNA transcription in CIK cells more than 100 times. Over-expression of gcIKKepsilon in EPC cells activated the promoter activity of both zebrafish IFN and fathead minnow IFN. gcIKKepsilon mRNA transcription level in CIK cells was increased from 48 h post GCRV infection with different MOIs. All the data support the idea that gcIKKepsilon is a novel teleost IkappaB kinase recruited in the IFN-mediated antiviral immunity of grass carp. PMID- 26370542 TI - The immune system is limited by oxidative stress: Dietary selenium promotes optimal antioxidative status and greatest immune defense in pacu Piaractus mesopotamicus. AB - Reactive oxygen species (ROS) are reactive molecules containing oxygen, that form as byproducts of aerobic metabolism, including immune system processes. Too much ROS may cause oxidative stress. In this study, we examined whether it can also limit the production of immune system compounds. To assess the relationship between antioxidant status and immunity we evaluated the effect of dietary supplementation with organic selenium, given at various levels for 10 days, on the antioxidant and immune system of the pacu fish (Piaractus mesopotamicus). Fish fed a diet containing 0.6 mg Se-yeast kg(-1) showed significant improvement in antioxidant status, as well as in hematological and immunological profiles. Specifically, they had the highest counts for catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST), red blood cells, and thrombocytes; the highest leukocyte count (particularly for monocytes); and the highest serum lysozyme activity. There was also a positive correlation between GPx and lysozyme in this group of fish. These findings indicate that short-term supplementation with 0.6 mg Se-yeast kg(-1) reestablished the antioxidative status, allowing the production of innate components which can boost immunity without the risk of oxidative stress. This study shows a relationship between oxidative stress and immunity, and, from a practical perspective, shows that improving immunity and health in pacu through the administration of selenium could improve their growth performance. PMID- 26370543 TI - Effect of APOE Gene Polymorphism on Early Cerebral Perfusion After Aneurysmal Subarachnoid Hemorrhage. AB - High mortality following aneurysmal subarachnoid hemorrhage (aSAH) occurs in the early phase, but the underlying mechanism of early brain injury (EBI) in aSAH was less elucidated. In this study, we aimed to investigate the association of apolipoprotein E (APOE) genotypes and early cerebral perfusion after aSAH. We collected venous blood of aSAH patients on admission for APOE genotype identification, applying computed tomography perfusion (CTP) scanning within 24 h after onset. The CTP parameters between patients with different APOE genotypes were compared. Then, a positive item was chosen for separate uni- and multivariate logistic regression analyses to seek its risk factors. Our results showed mean transit time (MTT) rather than other parameters was significantly longer in patients with the APOEepsilon4 allele, compared to those without APOEepsilon4 (6.45 +/- 1.17 versus 5.83 +/- 0.84 s, P = 0.019). APOEepsilon4 acted as an independent risk factor for MTT prolongation (>5.9 s) in uni- (P = 0.031, OR = 3.960, 95 % CI = 1.131-13.863) and multivariate (P = 0.019, OR = 9.822, 95 % CI = 1.458-66.193) logistic regression analyses, respectively. APOEepsilon4 may induce cerebral perfusion impairment in the early phase, contributing to EBI following aSAH, and assessment of APOE genotypes could serve as a useful tool in the prognostic evaluation and therapeutic management of aSAH. PMID- 26370544 TI - Phase 1 study of oral TAS-102 in patients with refractory metastatic colorectal cancer. AB - PURPOSE: To evaluate safety of TAS-102 administered twice daily (bid) on days 1-5 and 8-12 of a 4-week cycle, confirm feasibility of the Japanese recommended dose (RD), 35 mg/m(2), in Western patients with metastatic colorectal cancer (mCRC) refractory to standard chemotherapies, and describe preliminary antitumor activity. METHODS: This open-label, dose-escalation phase 1 study was conducted at four US centers. Patients were enrolled into two sequential cohorts [30 (cohort 1) or 35 mg/m(2)/dose bid (cohort 2)]; dose-limiting toxicities (DLT) were evaluated during cycle 1 in dose-escalation cohorts. At RD, 15 additional patients were enrolled in an expansion cohort. RESULTS: Patients (N = 27) with refractory mCRC received TAS-102; 74 % had received >=4 prior regimens. DLT was not observed in three patients in cohort 1, and was in one out of nine patients in cohort 2 (grade 3 febrile neutropenia). Therefore, RD was identified as 35 mg/m(2) bid. At RD, fatigue (63 %), gastrointestinal disturbances and nausea (46 %), vomiting (46 %), and diarrhea (42 %) were common but rarely grade 3/4. Grade 3/4 nausea, vomiting, and diarrhea occurred at 4 % each. Grade 3/4 toxicity was predominantly hematologic [neutropenia (71 %), anemia (25 %)]; febrile neutropenia was observed in two patients. Stable disease lasting >=6 weeks was achieved by 16 evaluable patients (70 %); median progression-free survival and overall survival were 5.3 and 7.5 months, respectively. CONCLUSIONS: TAS-102 has an acceptable safety profile and preliminary evidence of disease stabilization in Western patients with refractory mCRC. Results from a randomized phase 3 study have shown survival benefit with disease stabilization evidence in this population. PMID- 26370546 TI - Erratum to: dUTPase: the frequently overlooked enzyme encoded by many retroviruses. PMID- 26370545 TI - Comprehensive transcriptome analysis of Crocus sativus for discovery and expression of genes involved in apocarotenoid biosynthesis. AB - BACKGROUND: Crocus sativus stigmas form rich source of apocarotenoids like crocin, picrocrocin and saffranal which besides imparting color, flavour and aroma to saffron spice also have tremendous pharmacological properties. Inspite of their importance, the biosynthetic pathway of Crocus apocarotenoids is not fully elucidated. Moreover, the mechanism of their stigma specific accumulation remains unknown. Therefore, deep transcriptome sequencing of Crocus stigma and rest of the flower tissue was done to identify the genes and transcriptional regulators involved in the biosynthesis of these compounds. RESULTS: Transcriptome of stigma and rest of the flower tissue was sequenced using Illumina Genome Analyzer IIx platform which generated 64,604,402 flower and 51,350,714 stigma reads. Sequences were assembled de novo using trinity resulting in 64,438 transcripts which were classified into 32,204 unigenes comprising of 9853 clusters and 22,351 singletons. A comprehensive functional annotation and gene ontology (GO) analysis was carried out. 58.5 % of the transcripts showed similarity to sequences present in public databases while rest could be specific to Crocus. 5789 transcripts showed similarity to transcription factors representing 76 families out of which Myb family was most abundant. Many genes involved in carotenoid/apocarotenoid pathway were identified for the first time in this study which includes zeta-carotene isomerase and desaturase, carotenoid isomerase and lycopene epsilon-cyclase. GO analysis showed that the predominant classes in biological process category include metabolic process followed by cellular process and primary metabolic process. KEGG mapping analysis indicated that pathways involved in ribosome, carbon and starch and sucrose metabolism were highly represented. Differential expression analysis indicated that key carotenoid/apocarotenoid pathway genes including phytoene synthase, phytoene desaturase and carotenoid cleavage dioxygenase 2 are enriched in stigma thereby providing molecular proof for stigma to be the site of apocarotenoid biosynthesis. CONCLUSIONS: This data would provide a rich source for understanding the carotenoid/apocarotenoid metabolism in Crocus. The database would also help in investigating many questions related to saffron biology including flower development. PMID- 26370548 TI - Minutes of the Annual Business Meeting of the Members of the BEHAVIOR GENETICS ASSOCIATION : Friday, June 19, 2015, 12:15-1:15 pm, Salon A/B, Omni San Diego Hotel, San Diego, California. PMID- 26370547 TI - Dual Trajectories of Reactive and Proactive Aggression from Mid-childhood to Early Adolescence: Relations to Sensation Seeking, Risk Taking, and Moral Reasoning. AB - We examined the roles of sensation seeking, risk taking, and moral reasoning in the development of reactive and proactive aggression. Data were drawn from a multiethnic, longitudinal study of children from Switzerland (N = 1571; 52 % male; assessed annually over 6 years; 7-years-old at Time 1). At all 6 time points, teachers reported children's reactive and proactive aggression via questionnaire. Children's sensation seeking (at Time 1) and risk taking (at Time 2) were assessed with two interactive computer tasks and their moral reasoning was assessed at Time 2 in response to four hypothetical vignettes depicting moral transgressions. Parallel process Latent Class Growth Analysis (PP-LCGA) identified six dual trajectories of reactive and proactive aggression. Children with either childhood-limited or adolescent-onset aggression showed high sensation seeking. Children with persistent, high levels of both reactive and proactive aggression across time showed high levels of sensation seeking and risk taking, as well as low levels of moral reasoning. Children with only high risk taking were more likely to display moderate levels of aggression across time. These findings highlight the shared and differential roles of sensation seeking, risk taking, and moral reasoning in the dual development of reactive and proactive aggression from mid-childhood to early adolescence. We discuss implications for common and tailored strategies to combat these aggression subtypes. PMID- 26370549 TI - Awards Presented at the 45th Annual Meeting of the Behavior Genetics Association : Saturday, June 20, 2015, San Diego, CA, USA. PMID- 26370550 TI - Early mobilisation in intensive care units in Australia and Scotland: a prospective, observational cohort study examining mobilisation practises and barriers. AB - INTRODUCTION: Mobilisation of patients in the intensive care unit (ICU) is an area of growing research. Currently, there is little data on baseline mobilisation practises and the barriers to them for patients of all admission diagnoses. METHODS: The objectives of the study were to (1) quantify and benchmark baseline levels of mobilisation in Australian and Scottish ICUs, (2) compare mobilisation practises between Australian and Scottish ICUs and (3) identify barriers to mobilisation in Australian and Scottish ICUs. We conducted a prospective, observational, cohort study with a 4-week inception period. Patients were censored for follow-up upon ICU discharge or after 28 days, whichever occurred first. Patients were included if they were >18 years of age, admitted to an ICU and received mechanical ventilation in the ICU. RESULTS: Ten tertiary ICUs in Australia and nine in Scotland participated in the study. The Australian cohort had a large proportion of patients admitted for cardiothoracic surgery (43.3%), whereas the Scottish cohort had none. Therefore, comparison analysis was done after exclusion of patients admitted for cardiothoracic surgery. In total, 60.2% of the 347 patients across 10 Australian ICUs and 40.1% of the 167 patients across 9 Scottish ICUs mobilised during their ICU stay (p < 0.001). Patients in the Australian cohort were more likely to mobilise than patients in the Scottish cohort (hazard ratio 1.83, 95% confidence interval 1.38-2.42). However, the percentage of episodes of mobilisation where patients were receiving mechanical ventilation was higher in the Scottish cohort (41.1% vs 16.3%, p < 0.001). Sedation was the most commonly reported barrier to mobilisation in both the Australian and Scottish cohorts. Physiological instability and the presence of an endotracheal tube were also frequently reported barriers. CONCLUSIONS: This is the first study to benchmark baseline practise of early mobilisation internationally, and it demonstrates variation in early mobilisation practises between Australia and Scotland. PMID- 26370551 TI - Lack of Association Between Haptoglobin Phenotype and Cystic Fibrosis Outcomes. AB - Haptoglobin (Hp), a heme-Iron chelator, has different isoforms which are associated with variable tendency toward infections: Hp 1-1, Hp 2-1, and Hp 2-2. Cystic fibrosis (CF) outcomes are variable and influenced by genetic and environmental factors. The aim of this study was to determine whether Hp phenotype influenced disease severity in CF. One hundred forty-two CF patients from two centers were analyzed for Haptoglobin phenotype using gel electrophoresis of hemoglobin enriched serum. Clinical and microbiological data including bacterial colonization status, lung function, presence of CF-related diabetes and liver disease, rate of exacerbation, and mortality were compared between Hp phenotype groups. We found a trend toward less mucoid PA among Hp 2-2 (20.4 %) compared with Hp 1-1 and Hp 2-1 individuals (33.3 %), p = 0.317. Hp 2-2 individuals also had less antibiotic courses, and lower inflammatory markers without statistical significance. Haptoglobin phenotype is unlikely to be an important modifier of CF phenotype. PMID- 26370553 TI - Erratum to: Leadless Cardiac Pacemakers: Pacing Paradigm Change. PMID- 26370552 TI - Determinants of bacteriological outcomes in exacerbations of chronic obstructive pulmonary disease. AB - PURPOSE: Changes in sputum microbiology following antibiotic treatment of acute exacerbations of chronic obstructive pulmonary disease (AECOPD), including patterns of bacteriological relapse and superinfection are not well understood. Sputum microbiology at exacerbation is not routinely performed, but pathogen presence and species are determinants of outcomes. Therefore, we determined whether baseline clinical factors could predict the presence of bacterial pathogens at exacerbation. Bacterial eradication at end of treatment (EOT) is associated with clinical resolution of exacerbation. We determined the clinical, microbiological and therapeutic factors that were associated with bacteriological eradication in AECOPD at EOT and in the following 8 weeks. METHODS: Sputum bacteriological outcomes (i.e., eradication, persistence, superinfection, reinfection) from AECOPD patients (N = 1352) who were randomized to receive moxifloxacin or amoxicillin/clavulanate in the MAESTRAL study were compared. Independent predictors of bacterial presence in sputum at exacerbation and determinants for bacteriological eradication were analyzed by logistic regression and receiver operating characteristic (ROC) analyses. RESULTS: Significantly greater bacteriological eradication with moxifloxacin was mainly driven by superior Haemophilus influenzae eradication (P = 0.002, EOT). Baseline clinical factors were a weak predictor of the presence of pathogens in sputum (AUCROC = 0.593). On multivariate analysis, poorer bacterial eradication was associated with antibiotic resistance (P = 0.0001), systemic steroid use (P = 0.0024) and presence of P. aeruginosa (P = 0.0282). CONCLUSIONS: Since clinical prediction of bacterial presence in sputum at AECOPD is poor, sputum microbiological analysis should be considered for guiding antibiotic therapy in moderate-to-severe AECOPD, particularly in those who received concomitant systemic corticosteroids or are at risk for infection with antibiotic-resistant bacteria. PMID- 26370555 TI - Labile and Paroxysmal Hypertension: Common Clinical Dilemmas in Need of Treatment Studies. AB - Although "labile hypertension" is regularly encountered by clinicians, there is a paucity of information available to guide therapeutic decisions. This review discusses its clinical relevance, the limitations of current knowledge, and possible directions for future research and clinical management. Results of studies that assessed measures of blood pressure variability or reactivity are reviewed. The limited information about effects of antihypertensive drugs on blood pressure variability is discussed. Two different clinical presentations are differentiated: labile hypertension and paroxysmal hypertension. Labile hypertension remains a clinical impression without defined criteria or treatment guidance. Paroxysmal hypertension, also called pseudopheochromocytoma, presents as dramatic episodes of abrupt and severe blood pressure elevation. The disorder can be disabling. Although it regularly raises suspicion of a pheochromocytoma, such a tumor is found in <2 % of patients. The cause, which involves both emotional factors and the sympathetic nervous system, and treatment approaches, are presented. PMID- 26370556 TI - Follicular thyroglobulin enhances gene expression necessary for thyroid hormone secretion. AB - We have previously shown that follicular thyroglobulin (Tg) has an unexpected function as an autocrine negative-feedback regulator of thyroid hormone (TH) biosynthesis. Tg significantly suppressed the expression of genes necessary for iodide transport and TH synthesis by counteracting stimulation by TSH. However, whether follicular Tg also regulates intracellular TH transport and its secretion from thyrocytes is not known. In the present study, we examined the potential effect of follicular Tg on TH transport and secretion by quantifying the expression of two TH transporters: monocarboxylate transporter 8 (MCT8) and MU crystallin (CRYM). Our results showed that follicular Tg at physiologic concentrations enhanced both the mRNA and protein expression levels of MCT8 and CRYM in a time- and dose-dependent manner in rat thyroid FRTL-5 cells. Although both the sodium/iodide symporter (NIS), an essential transporter of iodide from blood into the thyroid, and MCT8, a transporter of synthesized TH from the gland, were co-localized on the basolateral membrane of rat thyrocytes in vivo, Tg decreased NIS expression and increased the expression of MCT8 by counteracting TSH action. Thus, the effect of Tg on TH secretion opposed its previously described negative-feedback suppression of TH synthesis. Our results indicate that Tg mediates a complex intrinsic regulation of gene expression that is necessary to balance two opposing vectorial transport systems: the inflow of newly synthesized TH and the outflow of TH by external secretion. PMID- 26370554 TI - CVD Prevention Through Policy: a Review of Mass Media, Food/Menu Labeling, Taxation/Subsidies, Built Environment, School Procurement, Worksite Wellness, and Marketing Standards to Improve Diet. AB - Poor diet is the leading cause of cardiovascular disease in the USA and globally. Evidence-based policies are crucial to improve diet and population health. We reviewed the effectiveness for a range of policy levers to alter diet and diet related risk factors. We identified evidence to support benefits of focused mass media campaigns (especially for fruits, vegetables, salt), food pricing strategies (both subsidies and taxation, with stronger effects at lower income levels), school procurement policies (for increasing healthful or reducing unhealthful choices), and worksite wellness programs (especially when comprehensive and multicomponent). Evidence was inconclusive for food and menu labeling (for consumer or industry behavior) and changes in local built environment (e.g., availability or accessibility of supermarkets, fast food outlets). We found little empiric evidence evaluating marketing restrictions, although broad principles and large resources spent on marketing suggest utility. Widespread implementation and evaluation of evidence-based policy strategies, with further research on other strategies with mixed/limited evidence, are essential "population medicine" to reduce health and economic burdens and inequities of diet-related illness worldwide. PMID- 26370557 TI - Pregnancy complications and glucose intolerance in women with polycystic ovary syndrome. AB - Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by insulin resistance and hyperandrogenism. The interaction of these factors might result in increased risks of miscarriage and pregnancy complications such as gestational diabetes mellitus (GDM). To examine the pregnancy risks in women with PCOS, we compared obstetrical outcomes between patients with and without PCOS. We also studied the differences in maternal characteristics, glucose intolerance and pregnancy complications between PCOS patients with and without GDM, with and without obesity, and between successful pregnancies and miscarriages. We observed a high incidence of GDM and prevalence of GDM diagnosis in the first trimester in PCOS. Patients with GDM had higher body mass index (BMI) and lower homeostasis model assessment of beta-cell function (HOMA-beta) at preconception than those without GDM. Obese pregnant women with PCOS demonstrated a high incidence of GDM with severe insulin resistance, including high fasting insulin, HOMA of insulin resistance (HOMA-IR), and HOMA-beta at preconception compared with normal-weight patients. BMI was significantly correlated with HOMA-IR or HOMA-beta, and both indices were lower in PCOS patients with than without GDM for the same BMI. There were no significant differences in maternal characteristics (excluding maternal age) between PCOS patients with successful pregnancy and PCOS patients with miscarriages. Our data suggest that pregnant women with PCOS have an increased risk of GDM, especially if they have obesity and/or poorer insulin secretion. Measure of beta-cell function, such as HOMA-beta, at preconception might be a useful predictor of the risk of GDM in pregnant PCOS patients. PMID- 26370558 TI - Validation and cross-cultural adaptation of the National Eye Institute Visual Function Questionnaire (NEI VFQ-25) in Serbian patients. AB - PURPOSE: To test the validity and reliability of the Serbian version of the interviewer-administered format of the National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25). METHODS: The Serbian version of NEI VFQ-25 was translated in accordance with standard methods that have been adopted internationally. In order to assess the reliability and validity of the translated NEI VFQ-25, we used a sample of 105 patients with four different chronic ocular diseases. Cronbach's alpha coefficient was used to assess internal consistency for each subscale. To assess test-retest reliability, intraclass correlation coefficients were used. The test-retest data were obtained from clinically stable patients with age-related cataracts, in surveys performed 2 weeks apart. Rasch analysis was also applied as a modern methods of psychometric assessment of the questionnaire. RESULTS: Four groups of patients were studied and the most prevalent were patients with cataract 40 (38.1%), followed by diabetic retinopathy 31 (29.5%), age related macular degeneration 22 (21.0%) and glaucoma 12 (11.4%). The overall index score on the NEI VFQ-25 ranged from 65.3 to 67.8 with a mean of 67.4 +/- 15.0. Cronbach's alpha coefficient (index of internal consistency reliability) ranged from 0.643 to 0.889 for the subscales. Evaluation of the validity of the Serbian version of NEI VFQ-25 is presented in the multi-trait-multi-method matrix and all items passed the convergent and discriminant validity tests. Rasch analysis showed a good measurement precision, but also demonstrated misfitting items and multidimensionality of the questionnaire. CONCLUSION: Although traditional validation method indicates that the Serbian version of NEI VFQ-25 is a valid and reliable instrument for the assessment of vision specific QoL in Serbian populations aged 40 years or older, Rasch analysis revealed a substantial weakness of the questionnaire that should be taken into consideration when interpreting the results. PMID- 26370559 TI - Ancient gene duplications have shaped developmental stage-specific expression in Pristionchus pacificus. AB - BACKGROUND: The development of multicellular organisms is accompanied by gene expression changes in differentiating cells. Profiling stage-specific expression during development may reveal important insights into gene sets that contributed to the morphological diversity across the animal kingdom. RESULTS: We sequenced RNA-seq libraries throughout a developmental timecourse of the nematode Pristionchus pacificus. The transcriptomes reflect early larval stages, adult worms including late larvae, and growth-arrested dauer larvae and allowed the identification of developmentally regulated gene clusters. Our data reveals similar trends as previous transcriptome profiling of dauer worms and represents the first expression data for early larvae in P. pacificus. Gene expression clusters characterizing early larval stages show most significant enrichments of chaperones, while collagens are most significantly enriched in transcriptomes of late larvae and adult worms. By combining expression data with phylogenetic analysis, we found that developmentally regulated genes are found in paralogous clusters that have arisen through lineage-specific duplications after the split from the Caenorhabditis elegans branch. CONCLUSIONS: We propose that gene duplications of developmentally regulated genes represent a plausible evolutionary mechanism to increase the dosage of stage-specific expression. Consequently, this may contribute to the substantial divergence in expression profiles that has been observed across larger evolutionary time scales. PMID- 26370560 TI - Standardized minimal acupuncture, individualized acupuncture, and no acupuncture for infantile colic: study protocol for a multicenter randomized controlled trial - ACU-COL. AB - BACKGROUND: Despite weak evidence, the use of acupuncture has increased in infantile colic. The only three randomized trials conducted evaluated standardized minimal acupuncture in one single point. Two showed effect but one did not so further research is necessary. The aims of the study are 1) to test if results in earlier trials conducted in private acupuncture clinics can be repeated at Child Health Centers (CHC) and 2) to compare the effect of two types of acupuncture and no acupuncture in infants with colic at CHC. METHODS/DESIGN: a multicenter randomized controlled three-armed trial for infantile colic conducted in four regions of Sweden. Alongside the standard program at their regular Child Health Center infants visit a study center twice a week for 2 weeks. The infants are randomly allocated into three groups. According to the power analysis, 144 otherwise healthy infants aged 2-9 weeks old, who - according to parents' registration in a diary - are crying and/or fussing more than three hours per day, more than 3 days per week will be included. Parents register daily in the diary during the baseline week, two intervention weeks, and one more week directly after the last study visit. At four study visits at the Child Health Center parents meet a nurse for 20-30 min to receive advice and support. The nurse and the parents are blinded for group allocation. Infants are carried to another room, where they spend five minutes with an acupuncturist. Infants randomized to group A receive standardized minimal acupuncture in LI4. Group B receive individualized acupuncture where, according to symptoms, the acupuncturist can choose between the points Sifeng, LI4, and ST36. Group C receives no acupuncture. The primary outcome is relative difference in crying, counted in minutes. Secondary outcomes are number of infants fulfilling the criteria for colic, and changes in sleep and stooling frequency. Adverse events and blinding are recorded. Recruitment started in January 2013. During the first 14 months 93 patients were included. Data collection continues until May 2015. No interim analyses have been conducted. DISCUSSION: The study will provide information about the efficacy and safety of acupuncture as a complement to usual care in infants with colic. TRIAL REGISTRATION: December 29, 2012: ClinicalTrials.gov NCT01761331. PMID- 26370561 TI - Nanotoxicology: advances and pitfalls in research methodology. AB - As research progresses, nanoparticles (NPs) are becoming increasingly promising tools for medical diagnostics and therapeutics. Despite this rise, their potential risks to human health, together with environmental issues, has led to increasing concerns regarding their use. As such, a comprehensive understanding of the interactions that occur at the nano-bio interface is required in order to design safe, reliable and efficient NPs for biomedical applications. To this end, extensive studies have been dedicated to probing the factors that define various properties of the nano-bio interface. However, the literature remains unclear and contains conflicting reports on cytotoxicity and biological fates, even for seemingly identical NPs. This uncertainty reveals that we frequently fail to identify and control relevant parameters that unambiguously and reproducibly determine the toxicity of nanoparticles, both in vitro and in vivo. An effective understanding of the toxicological impact of NPs requires the consideration of relevant factors, including the temperature of the target tissue, plasma gradient, cell shape, interfacial effects and personalized protein corona. In this review, we discuss the factors that play a critical role in nano-bio interface processes and nanotoxicity. A proper combinatorial assessment of these factors substantially changes our insight into the cytotoxicity, distribution and biological fate of NPs. PMID- 26370562 TI - O-linked N-acetylglucosamine glycosylation of p65 aggravated the inflammation in both fibroblast-like synoviocytes stimulated by tumor necrosis factor-alpha and mice with collagen induced arthritis. AB - INTRODUCTION: We investigated the inflammatory potential of O-linked N acetylglucosamine glycosylation (O-GlcNAcylation) of p65 in rheumatoid arthritis (RA). METHODS: Fibroblast-like synoviocytes (FLS) and MH7A cells were treated with synthetic ThiaMet-G (200 MUM), an O-GlcNAcase (OGA) inhibitor, followed by tumor necrosis factor (TNF)-alpha (10 MUg/mL). Proliferation of synovial cells was measured by MTT assay, and the levels of mRNAs encoding pro-inflammatory molecules were quantitated by RT-PCR. The nuclear localization of O-GlcNAcylated of p65 and its DNA binding affinity and transcriptional activity were assessed. The severity assessment of arthritis and a histopathological examination were done in mice with collagen induced arthritis (CIA). ThiaMet-G (20 mg/kg) intraperitoneal injection was done every other day for 26 days. Fluorescence activated cell sorting (FACS) analysis of T cells was performed. RESULTS: Hyper-O GlcNAcylation increased the proliferation and mRNA expression of pro-inflammatory genes in synoviocytes stimulated by TNF-alpha. Moreover, O-GlcNAcylation of p65 enhanced its proportion of nuclear localization, DNA binding affinity and transcriptional activity. In CIA mice, ThiaMet-G significantly aggravated the severity of arthritis clinically and histologically, and it also increased CD4 + IFN-gamma + T cells and CD4 + IL-17+ T cells. CONCLUSIONS: O-GlcNAcylation of p65 increased the effects of TNF-alpha-mediated inflammation both in vitro (in synovial cells) and in vivo (in mice with CIA). PMID- 26370563 TI - Inactivation of Heterosigma akashiwo in ballast water by circular orifice plate generated hydrodynamic cavitation. AB - The discharge of alien ballast water is a well-known, major reason for marine species invasion. Here, circular orifice plate-generated hydrodynamic cavitation was used to inactivate Heterosigma akashiwo in ballast water. In comparison with single- and multihole orifice plates, the conical-hole orifice plate yielded the highest inactivation percentage, 51.12%, and consumed only 6.84% energy (based on a 50% inactivation percentage). Repeating treatment, either using double series connection or circling inactivation, elevated the inactivation percentage, yet consumed much more energy. The results indicate that conical-hole-generated hydrodynamic cavitation shows great potential as a pre-inactivation method for ballast water treatment. PMID- 26370566 TI - Synthesis of P-stereogenic diarylphosphinic amides by directed lithiation: transformation into tertiary phosphine oxides via methanolysis, aryne chemistry and complexation behaviour toward zinc(ii). AB - The highly diastereoselective synthesis of P-stereogenic phosphinic amides via directed ortho lithiation (DoLi) of (SC)-P,P-diphenylphosphinic amides with t BuLi followed by electrophilic quench reactions is described. Functionalised derivatives containing a wide variety of ortho substituents (Cl, Br, I, OH, N3, SiMe3, SnMe3, P(O)Ph2, Me, allyl, (t)BuOCO) have been prepared in high yields with diastereomeric ratios up to 98 : 2. The X-ray diffraction structure of the ortho-stannylated and ortho-iodo compounds showed that the pro-S P-phenyl ring was stereoselectively ortho-deprotonated by the organolithium base. The usefulness of the method is supported by two key transformations, the synthesis of P-stereogenic methyl phosphinates through replacement of the chiral auxiliary by a methoxy group and the first example of the insertion of benzyne into the P-N bond of a P-stereogenic phosphinic amide. A DFT study of this reaction showed that the insertion proceeds through a [2 + 2] cycloaddition and a subsequent ring opening with retention of the P-configuration. Explorative coordination chemistry of the new P-stereogenic ligands provided access to a chiral phosphinic amide phosphine oxide Zn(ii) complex, the crystal structure of which is reported. PMID- 26370565 TI - Coordinated Dispersal and Pre-Isthmian Assembly of the Central American Ichthyofauna. AB - We document patterns of coordinated dispersal over evolutionary time frames in heroine cichlids and poeciliine live-bearers, the two most species-rich clades of freshwater fishes in the Caribbean basin. Observed dispersal rate (DO) values were estimated from time-calibrated molecular phylogenies in Lagrange+, a modified version of the ML-based parametric biogeographic program Lagrange. DO is measured in units of "wallaces" (wa) as the number of biogeographic range expansion events per million years. DO estimates were generated on a dynamic paleogeographic landscape of five areas over three time intervals from Upper Cretaceous to Recent. Expected dispersal rate (DE) values were generated from alternative paleogeographic models, with dispersal rates proportional to target area and source-river discharge volume, and inversely proportional to paleogeographic distance. Correlations between DO and DE were used to assess the relative contributions of these three biogeographic parameters. DO estimates imply a persistent dispersal corridor across the Eastern (Antillean) margin of the Caribbean plate, under the influence of prevailing and perennial riverine discharge vectors such as the Proto-Orinoco-Amazon river. Ancestral area estimation places the earliest colonizations of the Greater Antilles and Central America during the Paleocene-Eocene (ca. 58-45 Ma), potentially during the existence of an incomplete Paleogene Arc (~59 Ma) or Lesser Antilles Arc (~45 Ma), but predating the GAARlandia land bridge (~34-33 Ma). Paleogeographic distance is the single best predictor of DO. The Western (Central American) plate margin did not serve as a dispersal corridor until the Late Neogene (12-0 Ma), and contributed relatively little to the formation of modern distributions. PMID- 26370564 TI - Endocrine control of canine mammary neoplasms: serum reproductive hormone levels and tissue expression of steroid hormone, prolactin and growth hormone receptors. AB - BACKGROUND: Neoplasms of the mammary gland are among the most common diseases in female domestic dogs (Canis familiaris). It is assumed that reproductive hormones influence tumorigenesis in this species, although the precise role of the endocrine milieu and reproductive state is subject to continuing discussion. In line with this, a recent systematic review of available data on the development of mammary neoplasms revealed weak evidence for risk reduction after neutering and an effect of age at neutering. Investigation of several hormone receptors has revealed decreased expression of estrogen receptor-alpha (ERalpha, ESR1), progesterone (P4) receptor (PGR), prolactin (PRL) receptor (PRLR) and growth hormone receptor (GHR) associated with neoplastic differentiation of mammary tissues. In other studies, increased levels of estrogens, progesterone and prolactin were found in serum and/or tissue homogenates of dogs with malignant neoplasms. However, the association between these entities within one animal population was never previously examined. Therefore, this study investigated the association between circulating serum concentrations of estradiol-17beta, progesterone and prolactin, and gene expression of ERalpha (ESR1), ERbeta (ESR2), PGR, PRLR, PRL and GHR, with respect to reproductive state (spayed vs. intact) and cycle stage (anestrus vs. diestrus). Additionally, the expression of E cadherin (CDH-1) was evaluated as a possible indicator of metastatic potential. RESULTS: For all receptors, the lowest gene expression was found in malignant tumors compared to normal tissues of affected dogs. Steroid levels were not influenced by their corresponding receptor expression in mammary neoplasms, but increased PRL levels were negatively associated with low PRLR gene expression in malignant tumors. The expression of CDH-1 was influenced by tumor malignancy and cycle stage, i.e., the highest gene expression was found in benign mammary tumors in diestrous dogs compared to normal and malignant mammary tissues of anestrous and spayed dogs. CONCLUSIONS: Herein, it has been confirmed that transformation towards malignant neoplasms is associated with significant reduction of gene expression of particular hormone receptors. Only PRLR in malignant tumors seems to be influenced by circulating PRL levels. In dogs, CDH-1 can be used as a prognostic factor; its expression, however, in benign tumors is influenced by cycle stage. PMID- 26370567 TI - 1H, 13C, 15N resonance assignments of the extracellular loop 1 domain (ECL1) of Streptococcus pneumoniae D39 FtsX, an essential cell division protein. AB - FtsX is an integral membrane protein from Streptococcus pneumoniae (pneumococcus) that harbors an extracellular loop 1 domain (FtsX(Spn)ECL1) that interacts with PcsB, an peptidoglycan hydrolase that is essential for cell growth and division. Here, we report nearly complete backbone and side chain resonance assignments and a secondary structural analysis of FtsX(Spn)ECL1 (residues 47-168 of FtsX) as first steps toward structure determination of FtsX(Spn)ECL1. PMID- 26370568 TI - Uniform manganese hexacyanoferrate hydrate nanocubes featuring superior performance for low-cost supercapacitors and nonenzymatic electrochemical sensors. AB - Uniform manganese hexacyanoferrate hydrate nanocubes are prepared via a simple chemical precipitation method at room temperature. Due to both micro/mesopores of the Prussian blue analogue and nanocubic structures, the manganese hexacyanoferrate hydrate nanocubes allow the efficient charge transfer and mass transport for electrolyte solution and chemical species. Thus, the manganese hexacyanoferrate hydrate nanocube electrode shows a good rate capability and cycling stability for electrochemical capacitors. Furthermore, electrodes modified with manganese hexacyanoferrate hydrate nanocubes demonstrate a sensitive electrochemical response to hydrogen peroxide (H2O2) in buffer solutions with a high selectivity. PMID- 26370569 TI - Association Between Advances in High-Resolution Cross-Section Imaging Technologies and Increase in Prevalence of Pancreatic Cysts From 2005 to 2014. AB - BACKGROUND & AIMS: Increasingly, pancreatic cysts are discovered incidentally in patients undergoing cross-sectional imaging for nonpancreatic reasons. It is unclear whether this increase is caused by improved detection by progressively more sophisticated cross-sectional imaging techniques or by a true increase in prevalence. We aimed to determine the prevalence of incidental pancreatic cysts in patients undergoing magnetic resonance imaging (MRI) for nonpancreatic indications on successive, increasingly sophisticated MRI systems. Also, we compared prevalence based on the demographic characteristics of the patients. METHODS: We collected data from MRIs performed at the Mayo Clinic in Florida during the sample months of January and February, from 2005 to 2014. Each patient's clinical chart was reviewed in chronological order to include the first 50 MRIs of each year (500 total). Patients were excluded if they had pancreatic disease including cysts, pancreatic surgery, pancreatic symptoms, pancreatic indication for the imaging study, or previous abdominal MRIs. An expert pancreatic MRI radiologist reviewed each image, looking for incidental pancreatic cysts. RESULTS: Of the 500 patients analyzed, 208 patients (41.6%) were found to have an incidental cyst. A significant relationship was observed between pancreatic cysts and patient age (P < .0001), diabetes mellitus (P = .001), and nonpancreatic cancer (P = .01), specifically nonmelanoma skin cancer (P = .03) or hepatocellular carcinoma (P = .02). The multivariable model showed a strong association between hardware and software versions and detection of cysts (P < .0001); the old hardware detected pancreatic cysts in 30.3% of patients, whereas the newest hardware detected cysts in 56.3% of patients. CONCLUSIONS: Based on an analysis of data collected from 2005 through 2014, newer versions of MRI hardware and software corresponded with higher numbers of pancreatic cysts detected. Older age, diabetes, and the presence of nonpancreatic cancer (specifically nonmelanoma skin cancer and hepatocarcinoma) were also associated with the presence of cysts. PMID- 26370570 TI - McKittrick-Wheelock Syndrome. PMID- 26370571 TI - An early warning surveillance programme for detecting upper limb deterioration after treatment for breast cancer: A novel technology supported system. AB - Upper limb morbidity is a well-recognised consequence of treatment for breast cancer that can develop for up to 6 years after treatment. However, the capacity to fully integrate evidence-based rehabilitation pathways into routine care for all patients is questionable due to limited resources. A long term surveillance programme must therefore be accessible to all patients, should identify those at risk of developing morbidity and target the interventions at the high risk population of patients. The proposed model uses a surrogate marker for assessing risk of morbidity, incorporated into an Early Warning System (EWS), to produce a technology-lead, prospective surveillance programme. PMID- 26370572 TI - Reduced incidence of Crohn's disease in systemic sclerosis: a nationwide population study. AB - BACKGROUND: To date, there has been no studies to evaluate the incidence of Crohn's disease in systemic sclerosis patients. The goals of this study were to evaluate the incidence of Crohn's disease and its relationship with sex and age in patients with systemic sclerosis. METHODS: We enrolled patients with systemic sclerosis and controls from Taiwan's Registry of Catastrophic Illness Database and National Health Insurance Research Database. Every systemic sclerosis patient was matched to at most three controls by sex, age, month and year of initial diagnosis of systemic sclerosis. The standardized incidence ratio (SIR) of Crohn's disease in systemic sclerosis patients, and 95% confidence interval (95% CI) were calculated. Cox hazard regression was used to calculate the hazard ratio (HR). RESULTS: The study enrolled 2,829 patients with systemic sclerosis and 8,257 controls. Male and female patients with systemic sclerosis both had lower rates of incident Crohn's disease (SIR: 0.18, 95% CI = 0.05-0.62; SIR: 0.10, 95% CI = 0.05-0.21, respectively). The risk of incident Crohn's disease in systemic sclerosis was still lower than in controls when we stratified the patients according to their ages. In Cox hazard regression, the hazard rates of Crohn's disease were lower in systemic sclerosis patients after adjusting for genders and ages (HR: 0.12, 95% CI = 0.06-0.21, p < 0.001). CONCLUSIONS: Systemic sclerosis is associated with decreased incidence of, irrespective of sex and age of the patients. PMID- 26370573 TI - Comparison of Dental Explorers and CPI-probes in Diagnosing Dental Caries. AB - The primary aim of the present study was to compare efficiency in detecting suspected caries requiring observation (CO) and decayed teeth (DT) between dental explorers and Community Periodontal Index (CPI)-probes in school dental examinations and evaluate the effect of their respective use on Decayed, Missing, Filled Teeth (DMFT) Index scores. A total of 126 elementary and high school students were examined. All the clinical findings were obtained by a pair of trained dentists examining each student at routine annual school dental examinations. A dental explorer or CPI-probe and dental mirror were used for the examination. One dentist used the dental explorer, while the other used the CPI probe. The choice of which instrument to use by the first dentist to examine the student was made at random. A comparison of the explorers and CPI-probes revealed that the numbers of patients and permanent teeth classified as CO were greater with the former in 6th-grade elementary and high school students (p<0.05). The Kappa value for CO and DT was 0.560 for 6th-grade elementary school and 0.846 for high school students. All DMFT scores were higher with the explorers than with the CPI-probes in the 6th-grade elementary school students. No significant difference was observed between the explorers and CPI-probes in any of the DMFT scores in any group, however. The present results indicate that as long as the low rate of caries in Japanese school children is maintained, the epidemiological data on this disease should not show any significant change if a CPI-probe is used instead of an explorer in school dental examinations. PMID- 26370574 TI - Velocity of Canine Retraction in Angle Class I Treated with First Premolar Extraction: Effect of Facial Pattern. AB - Recently, new methods have been applied to increase velocity of tooth movement. A standard mean of tooth movement velocity remains to be established, however. Moreover, to our knowledge, no studies have investigated the effect of factors affecting this velocity. The aim of the present study was to investigate the effect of facial pattern on the mean velocity of canine retraction in selected cases of orthodontic treatment carried out at this hospital. A total of 112 patients with Angle Class I crowding treated with extraction of the bilateral maxillary and mandibular first premolars and a conventional edgewise bracket were selected at random. The canine retraction period was defined as that between the end of leveling and the beginning of anterior retraction, and was obtained from medical records. Calipers were used to measure how far the canine cusps moved between pre- and post-surgically on superimposed cephalometric tracings. The velocity of canine retraction was significantly slower in the maxilla of male patients with a brachyofacial pattern (p<0.01). Canine retraction is the longest stage of orthodontic treatment. Here, movement was slowest in the maxilla of male patients with a brachyofacial pattern. This indicates that treatment may take longer than average in male patients with a brachyofacial pattern, and that this should be explained prior to commencing such work. PMID- 26370576 TI - Determinant Factors in Locating Main Occluding Area on Dental Arch. AB - The purpose of this study was to investigate which were the most important factors in determining the location of the main occluding area by comparing its site on the dental arch between patients treated with implant-supported prostheses and those with a shortened dental arch (SDA). Twenty-five patients with Eichner B1 occlusion were enrolled in the study. The molar region in each quadrant was always edentulous. Fifteen patients were treated with implant prostheses, while the remaining 10 patients had SDA. Each patient was instructed to clench a piece of temporary stopping in the occluding area that was preferably used during mastication. The main occluding area was determined by locating the tooth on which the temporary stopping rested during clenching. The main occluding area was located ipsilaterally to the edentulous side in the molar region more often in the implant patients than in the SDA patients. The results of the present study suggest that the most important factor in determining the main occluding area is the presence of bilateral rigid molar occlusal support. PMID- 26370575 TI - Treatment Capabilities of Postgraduate Dental Trainees at Tokyo Dental College Suidobashi Hospital Based on Dental Services Income. AB - As of fiscal year 2006, it became compulsory for all newly licensed dentists in Japan to undergo a year of practical training at one of the designated training facilities found throughout the country as part of their postgraduate programs. The goal of this training is for the trainees to acquire diagnostic and therapeutic skills. While officially trainees, they are nonetheless regarded as members of staff. Clinical training emphasizes improving both technical skills and theoretical knowledge. However, taking on such trainees is sometimes considered unprofitable, as work productivity is claimed to be low. The purpose of this study was to compare work outcomes and income generated between trainees and part-time dentists working at the Tokyo Dental College Suidobashi Hospital. The part-time dentists comprised clinical instructors and dentists responsible for outpatients. Postgraduate dental trainees also generally conduct dental treatment for outpatients. Therefore, part-time dentists were considered the most suitable for a control group. No significant difference was observed in the total number of patients seen by either group by the final term of clinical training. Furthermore, no significant difference was observed in insurance-based dental treatment unit income (insured care unit income) per patient between the two groups from the mid-term period of training onwards. These results suggest that, although the trainees were less efficient in terms of time taken to provide a diagnosis and treatment, their performance was almost equal when viewed from the viewpoint of insured care provided. Taken together, this suggests that time related care efficiency must be increased and specific training policies and strategies developed to improve the work productivity of dental trainees. PMID- 26370577 TI - Microscopic Endodontics in Infected Root Canal with Calcified Structure: A Case Report. AB - Calcium deposited within a root canal due to exogenous stimuli may hamper root canal treatment. In endodontic treatment, an operating microscope allows the conditions within the root canal to be directly viewed and evaluated. This report describes a case in which an operating microscope was used to facilitate the excision of a calcified structure from within a root canal at an early stage in the treatment of an infection. An 18-year-old man was referred to our clinic due to suspected chronic suppurative apical periodontitis of the right maxillary central incisor. Periapical radiography confirmed the presence of a radioopaque structure inside the root canal that was likely to pose an obstacle to endodontic treatment. After opening the pulp chamber, an operating microscope was used to directly confirm the presence of the calcified structure in the root canal, which was removed using an ultrasonic tip. The infected root canal was treated using calcium hydroxide. Two months later, closure of the apical foramen as a result of calcification of the apical foramen was confirmed and the root canal filled. Using an operating microscope to directly view a structure posing an obstacle to root canal treatment made it possible to perform an excision while avoiding risks such as canal perforation. PMID- 26370578 TI - Diagnosis and Endodontic Management of Fused Mandibular Second Molar and Paramolar with Concrescent Supernumerary Tooth Using Cone-beam CT and 3-D Printing Technology: A Case Report. AB - Supernumerary teeth in the molar area are classified as paramolars or distomolars based on location. They occur frequently in the maxilla, but only rarely in the mandible. These teeth are frequently fused with adjacent teeth. When this occurs, the pulp cavities may also be connected. This makes diagnosis and planning of endodontic treatment extremely difficult. Here we report a case of a mandibular second molar fused with a paramolar, necessitating dental pulp treatment. Intraoral and panoramic radiographs were obtained for an evaluation and diagnosis. Although the images revealed a supernumerary tooth-like structure between the posterior area of the mandibular second molar and mandibular third molar, it was difficult to confirm the morphology of the tooth root apical area. Subsequent cone-beam computed tomography (CBCT) revealed that the supernumerary tooth-like structure was concrescent with the root apical area of the mandibular second molar. Based on these findings, the diagnosis was a fused mandibular second molar and paramolar with a concrescent supernumerary tooth. A 3 dimensional (3-D) printer was used to produce models based on the CBCT data to aid in treatment planning and explanation of the proposed procedures to the patient. These models allowed the complicated morphology involved to be clearly viewed, which facilitated a more precise diagnosis and better treatment planning than would otherwise have been possible. These technologies were useful in obtaining informed consent from the patient, promoting 3-D morphological understanding, and facilitating simulation of endodontic treatment. PMID- 26370579 TI - Additional Glucose-PTS Induction in Streptococcus mutans Mutant Deficient in Mannose- and Cellobiose-PTS. AB - Streptococcus mutans utilizes maltooligosaccharides, including maltose derived from human dietary starch. We recently reported that the glucose phosphotransferase system (Glc-PTS) was also involved in the metabolism of glucose derived from intracellular maltooligosaccharides in S. mutans. The activity of the Glc-PTS was mediated by the mannose-(manLMN) and cellobiose-PTSs (celABRCD) in this organism. The purpose of this study was to identify which kind of glucose transporter was involved in this process. A celD, manLM, and glk triple mutant, cm6vU1, was constructed and its growth in maltose or glucose broth measured. When cm6vU1 cells were inoculated into a fresh glucose broth following prolonged incubation with glucose, their growth rate was greater than that in the initial inoculum. This suggested that an additional Glc-PTS was induced in these cells. To investigate this possibility, permeabilized S. mutans cells were constructed and Glc-PTS activity examined by photometrical assay method. Activity in the cells was higher in the secondary inocula than in the initial inocula. These results suggest that S. mutans possesses an additional as yet uncharacterized PTS transporter for glucose in addition to the mannose- and cellobiose-PTSs. PMID- 26370580 TI - Towards monitoring the sandflies (Diptera: Psychodidae) of Thailand: DNA barcoding the sandflies of Wihan Cave, Uttaradit. AB - Sandflies vary in their distributions and role in pathogen transmission. Attempts to record distributions of sandflies in Thailand have faced difficulties due to their high abundance and diversity. We aim to provide an insight into the diversity of sandflies in Thailand by (i) conducting a literature review, and (ii) DNA barcoding sandflies collected from Wihan Cave where eight morphologically characterized species were recorded. DNA barcodes generated for 193 sandflies fell into 13 distinct species clusters under four genera (Chinius, Idiophlebotomus, Phlebotomus and Sergentomyia). Five of these species could be assigned Linnaean species names unambiguously and two others corresponded to characterized morphospecies. Two species represented a complex under the name Sergentomyia barraudi while the remaining four had not been recognized before in any form. The resulting species checklist and DNA barcode library contribute to a growing set of records for sandflies which is useful for monitoring and vector control. PMID- 26370581 TI - Molecular mechanism for preQ1-II riboswitch function revealed by molecular dynamics. AB - Riboswitches are RNA molecules that regulate gene expression using conformational change, affected by binding of small molecule ligands. A crystal structure of a ligand-bound class II preQ1 riboswitch has been determined in a previous structural study. To gain insight into the dynamics of this riboswitch in solution, eight total molecular dynamic simulations, four with and four without ligand, were performed using the Amber force field. In the presence of ligand, all four of the simulations demonstrated rearranged base pairs at the 3' end, consistent with expected base-pairing from comparative sequence analysis in a prior bioinformatic analysis; this suggests the pairing in this region was altered by crystallization. Additionally, in the absence of ligand, three of the simulations demonstrated similar changes in base-pairing at the ligand binding site. Significantly, although most of the riboswitch architecture remained intact in the respective trajectories, the P3 stem was destabilized in the ligand-free simulations in a way that exposed the Shine-Dalgarno sequence. This work illustrates how destabilization of two major groove base triples can influence a nearby H-type pseudoknot and provides a mechanism for control of gene expression by a fold that is frequently found in bacterial riboswitches. PMID- 26370582 TI - Evidence for cooperative tandem binding of hnRNP C RRMs in mRNA processing. AB - The human hnRNP C is a ubiquitous cellular protein involved in mRNA maturation. Recently, we have shown that this protein specifically recognizes uridine (U) pentamers through its single RNA recognition motif (RRM). However, a large fraction of natural RNA targets of hnRNP C consists of much longer contiguous uridine stretches. To understand how these extended sites are recognized, we studied the binding of the RRM to U-tracts of 8-11 bases. In vivo investigation of internal translation activation of unr (upstream of N-ras) mRNA indicates that the conservation of the entire hnRNP C binding site, UC(U)8, is required for hnRNP C-dependent IRES activation. The assays further suggest a synergistic interplay between hnRNP C monomers, dependent on the protein's ability to oligomerize. In vitro spectroscopic and thermodynamic analyses show that isolated RRMs bind to (U)11 oligomers as dimers. Structural modeling of a ternary double RRM/RNA complex indicates additionally that two RRM copies can be accommodated on the canonical sequence UC(U)8. The proposed tandem RRM binding is in very good agreement with the transcriptome-wide recognition of extended U-tracts by full length hnRNP C, which displays a cross-linking pattern consistent with a positively cooperative RRM dimer binding model. PMID- 26370583 TI - FASTKD2 is an RNA-binding protein required for mitochondrial RNA processing and translation. AB - Mitochondrial RNA processing is an essential step for the synthesis of the components of the electron transport chain in all eukaryotic organisms, yet several aspects of mitochondrial RNA biogenesis and regulation are not sufficiently understood. RNA interactome capture identified several disease relevant RNA-binding proteins (RBPs) with noncanonical RNA-binding architectures, including all six members of the FASTK (FAS-activated serine/threonine kinase) family of proteins. A mutation within one of these newly assigned FASTK RBPs, FASTKD2, causes a rare form of Mendelian mitochondrial encephalomyopathy. To investigate whether RNA binding of FASTKD2 contributes to the disease phenotype, we identified the RNA targets of FASTKD2 by iCLIP. FASTKD2 interacts with a defined set of mitochondrial transcripts including 16S ribosomal RNA (RNR2) and NADH dehydrogenase subunit 6 (ND6) messenger RNA. CRISPR-mediated deletion of FASTKD2 leads to aberrant processing and expression of RNR2 and ND6 mRNA that encodes a subunit of the respiratory complex I. Metabolic phenotyping of FASTKD2 deficient cells reveals impaired cellular respiration with reduced activities of all respiratory complexes. This work identifies key aspects of the molecular network of a previously uncharacterized, disease-relevant RNA-binding protein, FASTKD2, by a combination of genomic, molecular, and metabolic analyses. PMID- 26370584 TI - Primary vesicoureteral reflux: A 26-year experience in a single centre. AB - AIM: To determine the nature of primary vesicoureteral reflux (VUR) and the association of VUR with hydronephrosis and renal damage. METHODS: The medical records of children <= 15 years diagnosed with VUR, attending the Department of Pediatrics, Prince of Songkla University, Thailand between 1987 and 2013 were reviewed. Renal ultrasound and technetium-99m dimercaptosuccinic acid renal scan (DMSA) results were examined to determine the severity of hydronephrosis and renal damage, respectively. RESULTS: There were 177 boys and 211 girls. 350 (90.2%) were diagnosed following urinary tract infection (UTI). The median (IQR) age at diagnosis of first VUR was 7.6 (4.3-12.2) months in boys and 18.6 (9.0 46.6) months in girls (P < 0.001). Renal ultrasound was performed in 340 patients. Hydronephrosis was found in 105 patients and 135 kidneys and 22.5% VUR kidneys and 11.0% non-VUR kidneys (P = 0.01). The severity of hydronephrosis was associated with VUR grade (44.2% of grades IV and V VUR had hydronephrosis vs 11.9% of grades I-III VUR, P < 0.001). DMSA was performed in 332 patients. Abnormalities were found in 30.1% VUR kidneys and 4.1% non-VUR kidneys (P < 0.001). Abnormal DMSA results were strongly associated with VUR grade (17.8% for VUR grades I-III vs 60.5% for VUR grades IV and V, P < 0.001). CONCLUSION: Primary VUR in this group was most commonly diagnosed following investigation of UTI and detected during infancy, earlier in boys. Hydronephrosis and renal damage were associated with severity of VUR. PMID- 26370585 TI - Successful melanoma triage by a virtual lesion clinic (teledermatoscopy). AB - BACKGROUND: A Virtual Lesion Clinic (VLC) using teledermatoscopy was established to improve efficiency of the melanoma referral pathway. OBJECTIVES: To assess diagnostic accuracy and to compare wait-times and costs of VLC and conventional clinics. METHODS: Patients with suspected melanoma referred from primary care into a publicly funded health system attended local skin imaging centres, rather than hospital outpatient clinics. A teledermatologist assessed each lesion choosing specialist assessment/excision, General Practitioner (GP) follow-up, to re-image in 3 months, or self-monitoring/no concern. RESULTS: 613 skin lesions in 310 patients were evaluated over 12 months. Median time between receipt of referral and attendance at the VLC was 9 days compared to 26.5 days for standard outpatient assessment. Sixty-six percent (404/613) of lesions were considered benign, and 12% (73/613) were suspicious for melanoma. Of 129 lesions excised, 98 were skin cancers including 48 histologically confirmed melanomas with one spitzoid tumour of unknown malignant potential (STUMP), i.e. one melanoma per 1.59 suspected lesions biopsied and one melanoma in every 12.8 referred to the service. There were 49 non-melanoma skin cancers (NMSC). Teledermatoscopic diagnosis of melanomas was found to have a positive predictive value (PPV) of 63%. Compared to the conventional clinic, cost reductions from running the VLC for 1 year were in excess of NZ$364,000 (or NZ$1174/patient seen). CONCLUSIONS: The VLC offered an efficient, accurate and cost effective way of processing suspected melanoma referrals to the public health system. PMID- 26370586 TI - Promotion of regulatory T cell induction by immunomodulatory herbal medicine licorice and its two constituents. AB - Regulatory T cells (Treg) play a critical role to control immune responses and to prevent autoimmunity, thus selective increase of Treg cells in vivo has broad therapeutic implications for autoimmune and inflammatory diseases. Licorice is a well-known herbal medicine used worldwide for over thousands of years, and accumulating evidence has shown its immunomodulatory potential. However, it is not clear whether licorice could regulate the induction and function of Treg cells. Here we found licorice extract could promote Treg cell induction, and then we used a rational approach to isolate its functional fractions and constituents. The results showed that two constituents, isoliquiritigenin and naringenin, promoted Treg cell induction both in vitro and in vivo. The effective fractions and two constituents of licorice also enhanced immune suppression of Treg cells, and they further reduced severity of DSS-induced colitis in mice. This study suggested that promotion of regulatory T cell induction could be an underlying mechanism of the historically and widely used herbal medicine licorice, providing its two effective molecules against autoimmune and inflammatory diseases. PMID- 26370587 TI - Phenytoin enhances the phosphorylation of epidermal growth factor receptor and fibroblast growth factor receptor in the subventricular zone and promotes the proliferation of neural precursor cells and oligodendrocyte differentiation. AB - Phenytoin is a widely used antiepileptic drug that induces cell proliferation in several tissues, such as heart, bone, skin, oral mucosa and neural precursors. Some of these effects are mediated via fibroblast growth factor receptor (FGFR) and epidermal growth factor receptor (EGFR). These receptors are strongly expressed in the adult ventricular-subventricular zone (V-SVZ), the main neurogenic niche in the adult brain. The aim of this study was to determine the cell lineage and cell fate of V-SVZ neural progenitors expanded by phenytoin, as well as the effects of this drug on EGFR/FGFR phosphorylation. Male BALB/C mice received 10 mg/kg phenytoin by oral cannula for 30 days. We analysed the proliferation of V-SVZ neural progenitors by immunohistochemistry and western blot. Our findings indicate that phenytoin enhanced twofold the phosphorylation of EGFR and FGFR in the V-SVZ, increased the number of bromodeoxyuridine (BrdU)+/Sox2+ and BrdU+/doublecortin+ cells in the V-SVZ, and expanded the population of Olig2-expressing cells around the lateral ventricles. After phenytoin removal, a large number of BrdU+/Receptor interacting protein (RIP)+ cells were observed in the olfactory bulb. In conclusion, phenytoin enhanced the phosphorylation of FGFR and EGFR, and promoted the expression of neural precursor markers in the V-SVZ. In parallel, the number of oligodendrocytes increased significantly after phenytoin removal. PMID- 26370588 TI - Tetraspanin 1 is involved in survival, proliferation and carcinogenesis of pancreatic cancer. AB - Pancreatic cancer (PCC) is one of the most difficult cancers to treat and the 10th leading cause of cancer-related death in worldwide. Studies have demonstrated that the tetraspanin 1 (Tspan1) is overexpressed in various cancers and may be a potential therapeutic strategy for the treatment of different cancers. However, the possible role of Tspan1 in PCC is still unknown. In the present study, our data revealed that the increased Tspan1 in PCC tissues was associated with the clinicopathological features and survival rate of PCC patient. We also investigated the effects of Tspan1 gene knockdown on the biological behavior of human PCC. The expression of Tspan1 (detected by immunohistochemistry, qRT-PCR and western blot analysis) derived from human PCC tissues and cell lines (AsPC-1 and PANC-1), were significantly elevated compared with those of the control (P<0.05). Transfection with siRNA-targeting Tspan1 significantly decreased proliferation, increased the apoptosis and reduced migration and invasion of AsPC-1 and PANC-1 cells. The present study demonstrated that Tspan1 plays an important role in PCC carcinogenic progression, including migration and invasion. The siRNA targeting of Tspan1 may be a potential therapeutic strategy for the treatment of PCC. PMID- 26370589 TI - The billion dollar business of being smart. PMID- 26370591 TI - [Dental Anomaly patterns (DAP). A New Way to Look at Malocclusion]. PMID- 26370590 TI - Association of insulin-like growth factor-binding protein-3 with radiotherapy response and prognosis of esophageal squamous cell carcinoma. AB - BACKGROUND: Insulin-like growth factor-binding protein-3 (IGFBP-3) is suggested to predict the radiosensitivity and/or prognosis of patients with esophageal squamous cell carcinoma (ESCC). The present study was designed to investigate the clinical and prognostic effects of IGFBP-3 on ESCC. METHODS: IGFBP-3 was detected by immunohistochemistry in paraffin-embedded tissues from 70 ESCC patients treated with radiotherapy alone and further examined by western blotting analysis in 10 pairs of fresh ESCC tissues and adjacent non-malignant esophageal specimens. Receiver operating characteristic (ROC) analysis was used to determine cut-off scores for tumor positivity and to evaluate patient survival status. The chi(2) test was performed to analyze the association of IGFBP-3 expression with clinical characteristics and radiotherapy response. Associations between prognostic outcomes and IGFBP-3 expression were investigated using Kaplan-Meier analysis and the Cox proportional hazards model. RESULTS: The threshold for IGFBP 3 positivity was set to greater than 65% [area under the ROC curve (AUC)=0.690, P<0.019]. Of the 70 ESCC patient tissues tested, 32 (45.7%) were defined as having high IGFBP-3 expression. The levels of IGFBP-3 protein expression were decreased in 70.0% (7 of 10) of ESCC tissues compared with adjacent non-malignant esophageal tissue. In addition, IGFBP-3 expression was associated with pathologic classification (P<0.05 for T, N, and M categories and clinical stage). Patients with elevated protein level of IGFBP-3 in the tumor had an improved radiotherapy response and prolonged overall survival (P<0.001). CONCLUSIONS: High level of IGFBP-3 expression in ESCC associates with early clinical stages and are predictive for favorable survival of the patients treated with radiotherapy. PMID- 26370592 TI - [Relations between extraction of wisdom teeth and temporomandibular disorders: a case/control study]. AB - The aim of this study was to assess the impact of extraction of third molars on the occurrence of temporo-mandibular disorders (TMD). A review of the literature and a case-control study have been conducted. The case-control study compares the frequency of extraction of third molars between the sample with TMD (case) and the sample without TMD (control). The proportion of patients who had undergone extractions of wisdom teeth was higher in the case group than in the control group. The difference was statistically significant when patients had undergone extraction of all four wisdom teeth or when the extraction of four wisdom teeth underwent in one sitting or under general anesthesia. The study of patients in case sample shows that all signs of TMD were more common in patients who had undergone extractions in several sessions and under local anesthesia. The temporomandibular joint sounds are significantly more frequent with local anesthesia. In the case group, 85 to 92% of patients have parafunctions and 5 to 11% have malocclusion. This demonstrates the multifactorial etiology of temporomandibular disorders. PMID- 26370593 TI - [Innovations in diagnosis and treatment about a case of primary failure eruption linked to a PTHR1 gene mutation]. AB - Primary failure of eruption is a rare condition marked by non-eruption of the posterior teeth due to mutation of a gene responsible for tooth eruption. Today, this anomaly can be detected early using innovative 3D-imaging techniques. Genetic and histologic testing will confirm the diagnosis and unfavorable prognosis. Alveolar growth must be followed in other areas too in order to avoid structural and functional asymmetry. An analysis of the diagnostic and therapeutic options using bone-borne anchorage is presented via the long-term monitoring of a female patient presenting primary failure of eruption linked to mutation of the PTHR1 gene. PMID- 26370594 TI - [Increased susceptibility for white spot lesions by surplus orthodontic etching exceeding bracket base area]. AB - INTRODUCTION: There is a paucity of information with regard to the susceptibility of iatrogenic white spot lesion formation after inattentive, surplus orthodontic etching with 30% phosphoric acid and the subsequent provision or absence of adequate oral hygiene. METHODS: Ninety sound enamel specimens were randomly allocated to 6 trial groups (N = 15 each) for etching with 30% phosphoric acid for either 15 seconds and standardized daily enamel brushing or no brushing, etching for 30 seconds with daily brushing or no brushing, or nonetched controls with brushing or no brushing. Nutritive acidic assaults were simulated by demineralization cycles 3 times per day for 1 hour with interim storage in artificial saliva. Lesion depths in terms of percentage of fluorescence loss (delta F, delta Q) and lesion extension compared with the baseline were assessed by using quantitative light-induced fluorescence after 2, 7, 14, 21, and 42 days. Etching duration, trial time elapse, and oral hygiene, as well as the significance of factor interactions, were analyzed with 3-way analysis of variance (alpha=5%). RESULTS: The impact of the factors of enamel brushing, trial time elapse, and etching each had a comparably significant effect on lesion progression. The effect of surplus etching on white spot lesion formation was significantly enhanced by the simultaneous absence of enamel brushing and also the progression of trial time. The combination of 30 seconds of surplus etching with inadequate oral hygiene was especially detrimental. CONCLUSIONS: Excessive surplus orthodontic etching of the complete labial enamel surface, instead of the bracket bases only, must be avoided to prevent iatrogenic white spot lesions. Etching times not exceeding 15 seconds are favorable. PMID- 26370595 TI - [Comparison of the dental measurements according to the obstructive character of the tonsils]. AB - INTRODUCTION: The role of obstructive tonsils in dental arches abnormalities is widely discussed in the literature but remains controversial. Data on the probable relationship between obstructive tonsils and the presence of these orthodontic abnormalities are subjective. The objective of this study is to quantify the relationship between the obstructive character of the tonsils and the dental arches measurements. MATERIALS AND METHODS: A cross-sectional study was performed in children aged between 6 to 12 years divided into 2 groups (A and B) according to the obstructive character of the tonsils. Dental intra- and inter arches measurements are recorded on each child. Data is analyzed using SPSS 20.0 for Windows. A t Student and chi square tests are respectively used to compare quantitative and qualitative variables according to the obstructive character of the tonsils. The level of significance is fixed at p = 0.05. RESULTS: The upper dental arch depth is significantly more important in subjects with obstructive tonsils (group B). Dental arches widths are significantly more important in subjects without obstructive tonsils (group A). Group B subjects are significantly more likely to have class II malocclusions, open bite and posterior cross bite with mandibular lateral deviation than group A subjects. CONCLUSION: Early evaluation of children with obstructive tonsils can prevent dental intra- and inter-arches abnormalities caused by upper airway obstruction. Thus late and more aggressive treatments which are not always as efficient as when they were performed during childhood will be avoided. PMID- 26370596 TI - [Brackets and friction in orthodontics: experimental study]. AB - Many authors have been involved in developing brackets in order to improve the quality, stability, speed and efficiency of orthodontic treatment. In order to reduce friction between bracket and archwire, new therapeutic approaches have been devised based on novel technologies. Among these innovative techniques, self ligating brackets are increasingly popular. SLBs can be classified into several categories according to their mode of action and their materials. We performed an experimental study to compare the friction forces generated during the sliding of orthodontic archwires made from various alloys through conventional and self ligating brackets. Results show the favorable influence of SLBs, compared to conventional systems using elastomeric or metal ligatures, on the level of friction, particularly when shape-memory Ni-Ti archwires are used. PMID- 26370597 TI - Identification and description of controlled clinical trials published in Physiotherapy journals in Spain. AB - RATIONALE AND OBJECTIVES: The quantity and quality of research in physiotherapy has increased exponentially during the past decades. However, retrieving publications associated with this field of research is difficult. The aim of this study is to identify and describe controlled clinical trials (CCT) published in Spanish physiotherapy journals using electronic and handsearching strategies. METHOD: Observational study through which we identified eligible journals in order to retrieve CCTs using electronic and handsearching strategies, as proposed by the Cochrane Collaboration. A descriptive analysis of the main characteristics of these CCTs was completed. RESULTS: Seventy-eight CCTs were identified in 10 eligible journals, none of which were indexed in the major databases. 16.7% of the identified studies were multicentric. Traumatology and orthopaedics was the most studied field (33.3%) followed by neurology (15.4%). The most researched health problems were back pain (17.24%) fibromyalgia, arthrosis and stroke (6.8% each). Measured outcomes varied greatly, including pain control, functional mobility and quality of life. Most CCTs (64.1%) had a high risk of bias. CONCLUSIONS: The number of CCTs published in Spanish physiotherapy journals is limited. Handsearching these journals is essential, since none is indexed in major databases. In general, the identified CCTs carry a high risk of bias. PMID- 26370599 TI - Transgender Inmates in Prisons. AB - Transgender inmates provide a conundrum for correctional staff, particularly when it comes to classification, victimization, and medical and health issues. Using LexisNexis and WestLaw and state Department of Corrections (DOC) information, we collected state statutes and DOC policies concerning transgender inmates. We utilized academic legal research with content analysis to determine whether a statute or policy addressed issues concerning classification procedures, access to counseling services, the initiation and continuation of hormone therapy, and sex reassignment surgery. We found that while more states are providing either statutory or policy guidelines for transgender inmates, a number of states are lagging behind and there is a shortage of guidance dealing with the medical issues related to being transgender. PMID- 26370600 TI - Predictors of 30-day morbidity and mortality in transnasal microscopic pituitary tumor excision. AB - BACKGROUND: There is a lack of population-based, multi-institutional analyses of factors associated with morbidity and mortality following pituitary tumor excision. METHODS: The American College of Surgeons National Surgical Quality Improvement Project files were used to compile information on patients that had undergone transnasal microscopic pituitary tumor resection from 2006 to 2012. Patient demographics, comorbidities, operative characteristics, and morbidity and mortality in the 30 days following surgery were included. Multivariate logistic regression was used for categorical variables and multivariate linear regression was used for continuous variables to evaluate factors leading to adverse events. RESULTS: A total of 658 patients were included, of which 58 (8.81%) experienced a complication, reoperation or death in the 30 days following surgery. The most common complications were reoperation (3.37%), followed by unplanned reintubation (1.99%), urinary tract infection (1.68%), and transfusion (1.68%). Predictors of any complication, reoperation, or death include preoperative sepsis (odds ratio [OR] = 7.596) and lower preoperative serum albumin (OR = 6.667). Younger age predicted surgical complications (OR = 1.105). Predictors of medical complications include higher body mass index (OR = 1.112), chronic steroid use (OR = 6.568), preoperative sepsis (OR = 15.297), and lower preoperative serum hematocrit (OR = 1.225). Predictors of increased total length of hospital stay were older age (beta = 0.146), higher body mass index (beta = 0.188), chronic steroid use (beta = 0.142), preoperative sepsis (beta = 0.489), and lower preoperative serum albumin (beta = -0.213). CONCLUSION: Although adverse events following pituitary tumor excision are low, awareness of factors associated with morbidity and mortality in the early postoperative period may allow for improved patient monitoring and outcomes. PMID- 26370601 TI - Oztag: high risk for hand injuries? AB - BACKGROUND: Oztag is an Australian tag rugby code in which opponents are 'tackled' by removing Velcro tabs from their shorts. It is assumed to be safer than other higher-contact rugby codes. METHODS: Oztag-related hand injuries were identified by a word search of the electronic emergency department records of Concord Repatriation General Hospital from January 2011 to October 2013. Clinical records were retrospectively reviewed. RESULTS: Twenty-eight presentations were identified. Mean age of patients was 24 years (range 13-38). Injuries included fractures, dislocations and ligamentous injuries, in isolation or combination. The most common injuries were middle phalangeal fractures (six), all of which required operative fixation. No tendon avulsions were identified. The most common mechanism of injury was attempted tackle, which was much more likely to require operative management than any other mechanism (70% versus 14%, P = 0.010). CONCLUSIONS: While the prevalence of Oztag-related hand injuries may be low, the occurrence of potentially debilitating injuries in a young, working population raises concern. The 'tag' tackle, which involves players running at speed with outstretched fingers, is particularly high risk. Prospective audit of injuries is required and players and organizers should be made aware of the dangers of this 'low-contact' sport. PMID- 26370602 TI - Abnormalities in neuroendocrine stress response in psychosis: the role of endocannabinoids. AB - The aim of this article is to summarize current evidence regarding alterations in the neuroendocrine stress response system and endocannabinoid system and their relationship in psychotic disorders such as schizophrenia. Exposure to stress is linked to the development of a number of psychiatric disorders including psychosis. However, the precise role of stress in the development of psychosis and the possible mechanisms that might underlie this are not well understood. Recently the cannabinoid hypothesis of schizophrenia has emerged as a potential line of enquiry. Endocannabinoid levels are increased in patients with psychosis compared with healthy volunteers; furthermore, they increase in response to stress, which suggests another potential mechanism for how stress might be a causal factor in the development of psychosis. However, research regarding the links between stress and the endocannabinoid system is in its infancy. Evidence summarized here points to an alteration in the baseline tone and reactivity of the hypothalamic-pituitary-adrenal (HPA) axis as well as in various components of the endocannabinoid system in patients with psychosis. Moreover, the precise nature of the inter-relationship between these two systems is unclear in man, especially their biological relevance in the context of psychosis. Future studies need to simultaneously investigate HPA axis and endocannabinoid alterations both at baseline and following experimental perturbation in healthy individuals and those with psychosis to understand how they interact with each other in health and disease and obtain mechanistic insight as to their relevance to the pathophysiology of schizophrenia. PMID- 26370603 TI - Role of 'angle of progression' in prediction of delivery mode. AB - AIM: The aim of this study was to investigate the role of the 'angle of progression' (AOP) in the prediction of vaginal delivery. MATERIAL AND METHODS: In this prospective study, we followed 70 singleton pregnant women. AOP was measured at admission time and also at the beginning of the second stage immediately after digital examination. Digital and ultrasound examiners were unaware of each other's results. The digital examiner decided on the delivery mode based on clinical assessment. RESULTS: Sixty-five (92.9%) women had vaginal delivery. In the first stage of labor, the area under the curve was 87.5% (95% confidence interval [CI], 77.9-97.1; P = 0.005) for the AOP and 85.5% (95%CI, 75.2-95.6; P = 0.009) for digital examination and in the second stage of labor, the area under the curve was 90.2% (95%CI, 81-99.3; P = 0.003) for the AOP and 94.9% (95%CI, 89.1-100; P = 0.001) for digital examination. An AOP of >=113 degrees at the second stage was associated with a 90.8% probability of vaginal delivery. CONCLUSION: We found a significant relation between AOP and cervical dilatation during the first stage of labor. A larger angle at the beginning of the second stage was significantly associated with shorter time to delivery. PMID- 26370604 TI - Breast cancer: Doubtful health benefit of screening from 40 years of age. PMID- 26370605 TI - Breast cancer: Tracking ctDNA to evaluate relapse risk. PMID- 26370606 TI - Prostate cancer: AS-contemplation, not intervention. PMID- 26370607 TI - Risk factors: What do breast and CRC cancers and MS have in common? PMID- 26370608 TI - Enantioseparation of Mandelic Acid Enantiomers With Magnetic Nano-Sorbent Modified by a Chiral Selector. AB - In this study, R(+)-alpha-methylbenzylamine-modified magnetic chiral sorbent was synthesized and assessed as a new enantioselective solid phase sorbent for separation of mandelic acid enantiomers from aqueous solutions. The chemical structures and magnetic properties of the new sorbent were characterized by vibrating sample magnetometry, transmission electron microscopy, Fourier transform infrared spectroscopy, and dynamic light scattering. The effects of different variables such as the initial concentration of racemic mandelic acid, dosage of sorbent, and contact time upon sorption characteristics of mandelic acid enantiomers on magnetic chiral sorbent were investigated. The sorption of mandelic acid enantiomers followed a pseudo-second-order reaction and equilibrium experiments were well fitted to a Langmuir isotherm model. The maximum adsorption capacity of racemic mandelic acid on to the magnetic chiral sorbent was found to be 405 mg g(-1). The magnetic chiral sorbent has a greater affinity for (S)-(+) mandelic acid compared to (R)-(-)-mandelic acid. The optimum resolution was achieved with 10 mL 30 mM of racemic mandelic acid and 110 mg of magnetic chiral sorbent. The best percent enantiomeric excess values (up to 64%) were obtained by use of a chiralpak AD-H column. PMID- 26370609 TI - Stressors social support and elder mistreatment. AB - OBJECTIVES: This study sought to examine the pathways through which interpersonal relationship strain and loneliness (stressors) influence elder mistreatment. In addition, the study tested the buffer effects of social support within the stressor-mistreatment relationship. METHOD: Face-to-face interviews were conducted with 897 randomly selected older adults in rural Tamil Nadu, India. Mediation and moderation models were tested using the process module. RESULTS: Results showed that, in addition to the direct effects, interpersonal problems also influenced mistreatment via loneliness (partially mediating model). In the moderation model, social support buffered the influence of interpersonal strain on mistreatment (unconditional direct effect) and also buffered the influence of interpersonal strain on mistreatment through loneliness (conditional indirect effects). DISCUSSION: Intervention on mistreatment should involve elimination of risk factors and strengthening of social resources. PMID- 26370610 TI - Anti-irritant and anti-inflammatory effects of glycerol and xylitol in sodium lauryl sulphate-induced acute irritation. AB - BACKGROUND: Glycerol is known to possess anti-irritant and hydrating properties and previous studies suggested that xylitol may also have similar effects. OBJECTIVE: Our aim was to study whether different concentrations of these polyols restore skin barrier function and soothe inflammation in sodium lauryl sulphate (SLS)-induced acute irritation. METHODS: The experiments were performed on male SKH-1 hairless mice. The skin of the dorsal region was exposed to SLS (5%) for 3 h alone or together with 5% or 10% of glycerol respectively. Further two groups received xylitol solutions (8.26% and 16.52% respectively) using the same osmolarities, which were equivalent to those of the glycerol treatments. The control group was treated with purified water. Transepidermal water loss (TEWL) and skin hydration were determined. Microcirculatory parameters of inflammation were observed by means of intravital videomicroscopy (IVM). Furthermore, accumulation of neutrophil granulocytes and lymphocytes, the expression of inflammatory cytokines and SLS penetration were assessed, as well. RESULTS: Treatment with the 10% of glycerol and both concentrations of xylitol inhibited the SLS-induced elevation of TEWL and moderated the irritant-induced increase in dermal blood flow and in the number of leucocyte-endothelial interactions. All concentrations of the applied polyols improved hydration and prevented the accumulation of lymphocytes near the treatment site. At the mRNA level, neither glycerol nor xylitol influenced the expression of interleukin-1 alpha. However, expression of interleukin-1 beta was significantly decreased by the 10% glycerol treatment, while expression of tumour necrosis factor-alpha decreased upon the same treatment, as well as in response to xylitol. Higher polyol treatments decreased the SLS penetration to the deeper layers of the stratum corneum. CONCLUSION: Both of the analysed polyols exert considerable anti-irritant and anti-inflammatory properties, but the effective concentration of xylitol is lower than that of glycerol. PMID- 26370611 TI - Gene expression profile in the activation of subperitoneal fibroblasts reflects prognosis of patients with colon cancer. AB - Tumors can create a heterogenetic tumor microenvironment. We recently identified the pathologically unique cancer microenvironment formed by peritoneal invasion (CMPI), and revealed that subperitoneal fibroblasts (SPFs) within peritoneal tissue play a crucial role in tumor progression through their interaction with cancer cells. Therefore, the genes in SPFs altered by cancer stimulation may include some biologically important factors associated with patient prognosis. In this study, we aimed to identify new biomarkers using genes specifically upregulated in SPFs by cancer-cell-conditioned medium (CCCM) stimulation (SPFs CCCM response genes; SCR genes) in colon cancer (CC). We constructed two frameworks using SCR gene data: a publicly released microarray dataset, and validation cases with freshly frozen CC samples to identify genes related to short recurrence-free survival (RFS). In the first framework, we selected differentially expressed genes between the high and low SCR gene expression groups. In the second framework, genes significantly related to short RFS were selected by univariate analysis using all SCR genes, and multivariate analysis was performed to select robust genes associated with short RFS. We identified CTGF, CALD1, INHBA and TAGLN in the first framework, and PDLIM5, MAGI1, SPTBN1 and TAGLN in the second framework. Among these seven genes, high expression of three genes (CALD1, TAGLN and SPTBN1) showed a poor prognosis in our validation cases. In a public microarray dataset, SCR gene expression was associated with the expression of ECM component, EMT, and M2-macrophage associated genes, which was concordant with the pathological features of CMPI. Thus, we successfully identified new prognostic factors. PMID- 26370612 TI - Small leucine-rich proteoglycans (SLRPs): characteristics and function in the intervertebral disc. AB - The intervertebral disc (IVD) is responsible for normal spinal motion and load distribution. However, degeneration may occur due to age- and non-age-related processes and is primarily characterized by a reduction in the number of chondrocyte-like cells and abnormal extracellular matrix (ECM) structure in the nucleus pulposus. Although IVD progenitor cells have been identified, the local microenvironment components regulating the behaviour of these progenitor cell populations remain unknown. Small leucine-rich proteoglycans (SLRPs) are bioactive components of the ECM associated with fibrillogenesis, cellular growth and apoptosis and tissue remodelling. SLRPs support the survival of IVD progenitor cells under hypoxic conditions via the activation of specific hypoxia inducible factors. Additionally, SLRPs deficiency (biglycan) in knockout mice is sufficient to accelerate the IVD degenerative process. These data suggest that SLRPs play an important role in the homeostasis of IVD. Given their specific properties and physiological functions, we propose a role of SLRPs in IVD degeneration and potential application in its regeneration. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26370613 TI - Incidence and risk factors for myelofibrotic transformation among 272 Chinese patients with JAK2-mutated polycythemia vera. AB - Post-polycythemia vera myelofibrosis (post-PV MF) is a critical hematologic evolution of polycythemia vera (PV). The main purpose of the present study was to identify the possible risk factors for the occurrence and prognosis of post-PV MF in Chinese patients with PV. A cohort of 272 Chinese PV patients with JAK2(V617F) or exon12 mutation was retrospectively analyzed. Of the 272 patients with PV, 63 developed post-PV MF. Platelet count >550 * 10(9) /L and splenomegaly were identified as independent risk factors for post-PV MF. The median duration of survival for post-PV MF patients was 8 years. Anemia and age >65 years at diagnosis of post-PV MF were identified as significant predictors for the poor prognosis of post-PV MF. In conclusion, platelet counts and splenomegaly were significant predictors for the transformation to post-PV MF, while anemia (hemoglobin levels <100 g/L) and age>65 years were significant predictors for poor prognosis of post-PV MF in Chinese PV patients with JAK2(V617F) or exon12 mutation. PMID- 26370614 TI - Major histocompatibility complex class II genetic variation in forest musk deer (Moschus berezovskii) in China. AB - The major histocompatibility complex (MHC) plays an important role in the immune system of vertebrates. We used the second exon of four MHC class II genes (DRA, DQA1, DQA2 and DRB3) to assess the overall MHC variation in forest musk deer (Moschus berezovskii). We also compared the MHC variation in captive and wild populations. We observed 22 alleles at four loci (four at DRA, four at DQA1, four at DQA2 and 10 at DRB3), 15 of which were newly identified alleles. Results suggest that forest musk deer maintain relatively high MHC variation, which may result from balancing selection. Moreover, considerable diversity was observed at the DRA locus. We found a high frequency of Mobe-DRA*02, Mobe-DQA1*01 and Mobe DQA2*05 alleles, which may be important for pathogen resistance. A Ewens Watterson test showed that the DRB3 locus in the wild population had experienced recent balancing selection. We detected a small divergence at the DRA locus, suggesting the effect of weak positive selection on the DRA gene. Alternatively, this locus may be young and not yet adapted a wide spectrum of alleles for pathogen resistance. The significant heterozygosity deficit observed at the DQA1 and DRB3 loci in the captive population and at all four loci in the wild population may be the result of a population bottleneck. Additionally, MHC genetic diversity was higher in the wild population than in the captive, suggesting that the wild population may have the ability to respond to a wider range of pathogens. PMID- 26370616 TI - Multidimensional isotope analysis of carbon, hydrogen and oxygen as tool for identification of the origin of ibuprofen. AB - Multidimensional isotope profiling is a useful tool for the characterization of the provenance of active pharmaceutical ingredients (API). To evaluate this approach, samples of the nonsteroidal anti-inflammatory drug (NSAIDs) ibuprofen were collected from 32 manufactures and 13 countries, and carbon, hydrogen and oxygen isotope ratios were analyzed by elemental analyzer, chromium-filled elemental analyzer and high temperature conversion elemental analyzer (EA, Cr-EA and TC/EA) coupled to an isotope ratio mass spectrometry (IRMS). The range of isotope values of ibuprofen (delta(13)C: -33.2+/-0.10/00 to -27.4+/-0.10/00; delta(2)H: -121.4+/-1.50/00 to -41.2+/-0.80/00; and delta(18)O: -12.6+/-0.30/00 to 19.0+/-0.60/00) allowed characterization and distinction of 5 groups, which reflect synthetic pathways and/or use of different raw materials, as well as possible isotope fractionation during the synthesis reactions. This study highlights that multi isotope fingerprinting has potential for identification of sources, and provides a database of isotope composition of ibuprofen (delta(2)H, delta(13)C, delta(18)O) that might improve the tracing of origin, transport pathways and environmental fate of ibuprofen. PMID- 26370615 TI - The Anti-fibrotic Effects and Mechanisms of MicroRNA-486-5p in Pulmonary Fibrosis. AB - To identify microRNAs (miRNAs, miRs) with potential roles in lung fibrogenesis, we performed genome-wide profiling of miRNA expression in lung tissues from a silica-induced mouse model of pulmonary fibrosis using microarrays. Seventeen miRNAs were selected for validation via qRT-PCR based on the fold changes between the silica and the control group. The dysregulation of five miRNAs, including miR 21, miR-455, miR-151-3p, miR-486-5p and miR-3107, were confirmed by qRT-PCRs in silica-induced mouse model of pulmonary fibrosis and were also confirmed in a bleomycin (BLM)-induced mouse lung fibrosis. Notably, miR-486-5p levels were decreased in the serum samples of patients with silicosis, as well as in the lung tissues of patients with silicosis and idiopathic pulmonary fibrosis (IPF). In addition, as determined by luciferase assays and Western blotting, SMAD2, a crucial mediator of pulmonary fibrosis, was identified to be one of target genes of miR-486-5p. To test the potential therapeutic significance of this miRNA, we overexpressed miR-486-5p in animal models. At day 28, miR-486-5p expression significantly decreased both the distribution and severity of lung lesions compared with the silica group (P < 0.01). In addition, miR-486-5p had a similar effect in the BLM group (P < 0.001). These results indicate that miR-486-5p may inhibit fibrosis. PMID- 26370617 TI - Cardiac Rehabilitation for Hypertension Assessment and Control: Report From the International Council of Cardiovascular Prevention and Rehabilitation. PMID- 26370618 TI - Influence of Dissolved Organic Matter on Tetracycline Bioavailability to an Antibiotic-Resistant Bacterium. AB - Complexation of tetracycline with dissolved organic matter (DOM) in aqueous solution could alter the bioavailability of tetracycline to bacteria, thereby alleviating selective pressure for development of antibiotic resistance. In this study, an Escherichia coli whole-cell bioreporter construct with antibiotic resistance genes coupled to green fluorescence protein was exposed to tetracycline in the presence of DOM derived from humic acids. Complexation between tetracycline and DOM diminished tetracycline bioavailability to E. coli, as indicated by reduced expression of antibiotic resistance genes. Increasing DOM concentration resulted in decreasing bioavailability of tetracycline to the bioreporter. Freely dissolved tetracycline (not complexed with DOM) was identified as the major fraction responsible for the rate and magnitude of antibiotic resistance genes expressed. Furthermore, adsorption of DOM on bacterial cell surfaces inhibited tetracycline diffusion into the bioreporter cells. The magnitude of the inhibition was related to the amount of DOM adsorbed and tetracycline affinity for the DOM. These findings provide novel insights into the mechanisms by which the bioavailability of tetracycline antibiotics to bacteria is reduced by DOM present in water. Agricultural lands receiving livestock manures commonly have elevated levels of both DOM and antibiotics; the DOM could suppress the bioavailability of antibiotics, hence reducing selective pressure on bacteria for development of antibiotic resistance. PMID- 26370620 TI - Family caregivers require mental health specialists for end-of-life psychosocial problems at home: a nationwide survey in Japan. AB - BACKGROUND: Psychological distress is problematic for patients and their family caregivers in the oncological setting. The level of stress is influenced by the health status of the patient and their family members as well as the support system for home care. However, it remains unclear how best to support distressed caregivers providing end-of-life care at home. METHODS: The present study was performed as part of the Japan Hospice and Palliative Care Evaluation study among caregivers whose family members are provided home palliative care. The caregivers were asked whether they wished to receive psychological support from mental health specialists, and factors associated with the need for psychological support were analyzed. RESULTS: Of the 1052 caregivers, 628 completed the questionnaire. As a whole, 169 subjects [27%; 23-30% (95% confidence interval)] reported needing psychological support from a mental health specialist. According to a multiple regression analysis, factors associated with the need for psychological support included (1) emotional distress due to the need to adapt to rapid worsening of the patient's condition [adjusted odds ratio: 2.62 (95% CI 1.77-3.88), p < 0.001], (2) the poor health conditions of the caregivers [2.93 (1.61-5.36), p < 0.001], and (3) having someone else available to care for the patient in place of the caregiver [0.51 (0.34-0.78), p = 0.002]. CONCLUSIONS: Psychological support is required for caregivers tending to patients at home. Further studies are needed to construct a system to provide continuous support to caregivers. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26370619 TI - Germline polymorphisms in genes involved in the Hippo pathway as recurrence biomarkers in stages II/III colon cancer. AB - The Hippo pathway regulates tissue growth and cell fate. In colon cancer, Hippo pathway deregulation promotes cellular quiescence and resistance to 5 Fluorouracil (5-Fu). In this study, 14 polymorphisms in 8 genes involved in the Hippo pathway (MST1, MST2, LATS1, LATS2, YAP, TAZ, FAT4 and RASSF1A) were evaluated as recurrence predictors in 194 patients with stages II/III colon cancer treated with 5-Fu-based adjuvant chemotherapy. Patients with a RASSF1A rs2236947 AA genotype had higher 3-year recurrence rate than patients with CA/CC genotypes (56 vs 33%, hazard ratio (HR): 1.87; P=0.017). Patients with TAZ rs3811715 CT or TT genotypes had lower 3-year recurrence rate than patients with a CC genotype (28 vs 40%; HR: 0.66; P=0.07). In left-sided tumors, this association was stronger (HR: 0.29; P=0.011) and a similar trend was found in an independent Japanese cohort. These promising results reveal polymorphisms in the Hippo pathway as biomarkers for stages II and III colon cancer.The Pharmacogenomics Journal advance online publication, 15 September 2015; doi:10.1038/tpj.2015.64. PMID- 26370621 TI - The post-traumatic colour change of primary incisors: a colourimetric and longitudinal study. AB - BACKGROUND: Tooth colour change after trauma has been described subjectively as ranging from yellow/pink to grey/black. AIM: To investigate the longitudinal colourimetric change of post-traumatic discoloured primary incisor using an intraoral colourimeter. DESIGN: A total of 34 primary incisors from 15 boys and eight girls were studied. The mean post-injury day during clinic visits (SD) and number of visit was 205.4 (194.8) and 3.9 (2.0). CIE L* (lightness), a* (green red) and b* (blue-yellow) of the maxillary primary incisors were measured at every visit. The colour difference (DeltaE*ab ) was calculated between the traumatized tooth and the control. Scatter graphs were made depicting the colour change of discoloured teeth and the DeltaE*ab over time. RESULTS: Mean CIE L*, a* and b* of the unaffected control were 80.8 (2.29), 0.9 (0.77) and 13.1 (2.67), respectively. L* gradually decreased to 70.7 (on day 71), then slowly recovered. a* increased to 3.7 (day 29) and decreased slowly. b* only demonstrated a small change that was within the control range during the follow-up. DeltaE*ab increased to 9.58 (day 56) and decreased slowly. CONCLUSION: The earlier recovery of a* was followed by the recovery of L*. During the post-traumatic period, DeltaE*ab failed to reach the clinically acceptable threshold. PMID- 26370622 TI - Outcome of a new patient pathway for managing B3 breast lesions by vacuum assisted biopsy: time to change current UK practice? AB - AIMS: B3 lesions of the breast represent a difficult management dilemma. The umbrella term 'B3' incorporates lesions with little associated malignancy risk as well as lesions with significant risk of concurrent neoplasia. Diagnosis of B3 lesions in screening populations is largely made on needle core biopsy, which provides little tissue to adequately diagnose pathologically diverse lesions. The advent of vacuum-assisted biopsy (VAB) provides the multidisciplinary team with a more representative pathology sample to direct management. METHODS: In this unit, in 2009, a pathway to guide management of B3 lesions detected on needle core biopsy in screening patients was implemented to assess whether VAB was a safe and viable alternative to surgery in selected cases.Here we present the 5-year follow up results of this pathway. RESULTS: 398 patients with B3 lesions were suitable for this pathway, of which 321 went on to have second-line VAB. 24% of these patients subsequently required surgery for malignancy or ongoing concerns, and thus 245 avoided surgery being subsequently referred for 5-year mammographic surveillance or back to screening. Median follow-up was 3 years (IQR 2), and no cancers were detected at the original B3 site during follow-up. CONCLUSIONS: We have demonstrated here that with large volume tissue sampling for indeterminate lesions of the breast surgery can be safely avoided in selected B3 lesions with and without atypia. PMID- 26370623 TI - Maternal sensitivity and mental health: does an early childhood intervention programme have an impact? AB - BACKGROUND: Maternal sensitivity (MS) and mental health influence mother-child attachment and the child's mental health. Early interventions may promote resilience and facilitate healthy development of the children through an impact on mothers' outcomes such as their sensitivity and mental health. Play with Our Children (POC) is an early intervention programme aiming to promote a positive mother-child interaction for children who attend three family health centres of deprived areas of Santiago de Chile. OBJECTIVE: To estimate the effect of the programme POC on MS and mental health. METHODS: A quasi-experimental design with propensity score matching estimations was employed. MS was measured with the Q Sort of Maternal Sensitivity, and maternal mental health was assessed with the Patient Health Questionnaire and the Parenting Stress Index. Mean-difference comparison and difference-in-difference method were used as statistical strategies. The sample included 102 children from 2 to 23 months of age, 54 of them participated in the intervention and 48 children were the comparison group. RESULTS: Estimates showed that participation in POC was positively associated with less stress in mothers of children younger than 12 months (P < 0.05) and positively associated with MS for mothers of children from 12 to 23 months (P < 0.05). There were no significant differences in maternal depression scores. CONCLUSION: The dyadic early intervention POC may influence mother's mental health and indirectly impact children's well-being during critical stages of their development by strengthening their mother's sensitivity towards them. PMID- 26370625 TI - Effect of Estradiol valerate plus dienogest on body composition of healthy women in the menopausal transition: a prospective one-year evaluation. AB - In the menopausal transition (MT), combined oral contraceptive (COC) should be chosen accordingly to its neutrality on liver metabolism and to its ability to counter the increase of fat mass (FM) that occurs in this reproductive period of life. This prospective multi-centric observational study was conducted on 36 women in their MT at the Universities of Cagliari, Modena and Naples. The body weight (BW), the Body Mass Index (BMI), the waist to hip ratio (WHR), the measurement of body composition (BC) with the Multi-frequency Bioelectrical Impedance (MF-BIA) were performed before, at the 6th and at the 12th month of the study in which a group of women (control group; N.18) did not assume COC, whereas the other 18 women assumed the four-phasic COC containing estradiol valerate (EV) associated with dienogest (EV/DNG group). In comparison to controls in the EV/DNG group, a significant decrease (p < 0.05) of BW (58.8 +/- 7.6 to 57.3 +/- 7.0), BMI (24.1 +/- 2.7 to 23.5 +/- 2.8), WHR (0.82 +/- 0.052 to 0.79 +/- 0.048) and FM (17.7 +/- 5.4 to 16.4 +/- 5.6) was observed. In controls, FM significantly increased (17.0 +/- 11 to 17.7 +/- 2.7; p < 0.05). In conclusion, these results suggest that the anti-androgenic and progestinic activities of DNG associated with a weak estrogenic activity of EV, is a contraceptive method capable of counteracting the negative changes of BC occurring in the MT. PMID- 26370624 TI - Autoantibody Profiling of Glioma Serum Samples to Identify Biomarkers Using Human Proteome Arrays. AB - The heterogeneity and poor prognosis associated with gliomas, makes biomarker identification imperative. Here, we report autoantibody signatures across various grades of glioma serum samples and sub-categories of glioblastoma multiforme using Human Proteome chips containing ~17000 full-length human proteins. The deduced sets of classifier proteins helped to distinguish Grade II, III and IV samples from the healthy subjects with 88, 89 and 94% sensitivity and 87, 100 and 73% specificity, respectively. Proteins namely, SNX1, EYA1, PQBP1 and IGHG1 showed dysregulation across various grades. Sub-classes of GBM, based on its proximity to the sub-ventricular zone, have been reported to have different prognostic outcomes. To this end, we identified dysregulation of NEDD9, a protein involved in cell migration, with probable prognostic potential. Another subcategory of patients where the IDH1 gene is mutated, are known to have better prognosis as compared to patients carrying the wild type gene. On a comparison of these two cohorts, we found STUB1 and YWHAH proteins dysregulated in Grade II glioma patients. In addition to common pathways associated with tumourigenesis, we found enrichment of immunoregulatory and cytoskeletal remodelling pathways, emphasizing the need to explore biochemical alterations arising due to autoimmune responses in glioma. PMID- 26370626 TI - Many unique characteristics revealed by the complete mitochondrial genome of the scorpion Tityus serrulatus (Lutz e Mello 1922) (Chelicerata; Arachnida). AB - This is the first complete mitochondrial genome of a Tityus species, although it is the most medically important genus in South America. Tityus serrulatus (Brazilian yellow scorpion) mtDNA revealed the same gene arrangement of three out of four other mitogenomes published by now for the same family (Centruroides limpidus, Mesobuthus gibbosus, M. martensii and Buthus occitanus). However, it presented many unique characteristics such as possession of Cox1 gene, different from all other protein-coding genes of scorpion mtDNA, starts with an atypical start codon (CTG). Moreover, no tRNA gene have complete typical secondary structure and the Tytius genome presented three non-coding regions longer than 100bp. Also, it contains the smallest scorpion 16S gene reported by now. Phylogenetic analysis using concatenated homologous genes confirmed Buthidae as a monophyletic clade and supports a monophyletic group including T. serrulatus and the other American species, C. limpidus. PMID- 26370627 TI - Simulated Interactive Research Experiments as Educational Tools for Advanced Science. AB - Experimental research has become complex and thus a challenge to science education. Only very few students can typically be trained on advanced scientific equipment. It is therefore important to find new tools that allow all students to acquire laboratory skills individually and independent of where they are located. In a design-based research process we have investigated the feasibility of using a virtual laboratory as a photo-realistic and scientifically valid representation of advanced scientific infrastructure to teach modern experimental science, here, molecular quantum optics. We found a concept based on three educational principles that allows undergraduate students to become acquainted with procedures and concepts of a modern research field. We find a significant increase in student understanding using our Simulated Interactive Research Experiment (SiReX), by evaluating the learning outcomes with semi-structured interviews in a pre/post design. This suggests that this concept of an educational tool can be generalized to disseminate findings in other fields. PMID- 26370628 TI - Solitary jejunal metastasis from renal cell carcinoma presenting as small bowel obstruction 19 years after nephrectomy. AB - Metachronous metastatic disease may develop in up to 50% of patients with renal cell carcinoma (RCC) who have undergone a presumably curative radical nephrectomy. We describe a case of small bowel obstruction secondary to a solitary jejunal RCC metastasis affecting a 66-year-old man with a history of RCC, which was treated 19 years earlier by right radical nephrectomy. The patient underwent successful laparotomy and wide margin resection of the affected small bowel with end-to-end anastomosis. A subsequent staging CT revealed no other metastases. To our knowledge, only eight cases of isolated small bowel metastasis from RCC have been reported. Of these, only one previous report referred to a longer time interval to small bowel metastasis than our case. The case highlights that isolated bowel metastasis should be considered as a possible aetiology of small bowel obstruction, even in patients with a distant history of presumably curative cancer treatment. PMID- 26370629 TI - Benign cystic mesothelioma of the peritoneum in a 12-year-old boy, diagnosed via telepathology. AB - Low resource countries often have inadequate healthcare systems that, among other problems, suffer from a severe shortage of local expertise. In fields such as pathology, however, where diagnoses are mainly based on macroscopic and histological images, telemedicine can provide an opportunity to supplement the local capabilities by involving a world-wide network of experts. For this, the local pathologist can upload images to an online platform and then consult with international colleagues via teleconferencing, which can be particularly useful in rare or difficult cases. We present the case of a 12-year-old Afghan boy with benign cystic mesothelioma, an extremely rare benign tumour. Using the online platform IPath, we were able to diagnose the eighth reported case of this rare condition in a child, in collaboration with our colleagues in Afghanistan. PMID- 26370630 TI - Inhaled treprostinil via the Tyvaso Inhalation System through a tracheostomy. AB - A 20-year-old man with pulmonary arterial hypertension secondary to systemic sclerosis was admitted to our hospital. Prior to admission, his PAH had been successfully managed with the use of tadalafil, ambrisentan and inhaled Tyvaso. Owing to respiratory failure from vocal cord paralysis, he underwent an emergent tracheotomy. The delivery of inhaled Tyvaso through a tracheostomy tube was explored. Post-tracheostomy, the patient continued his ability to self-administer the medication. His WHO functional classification, brain natriuretic peptide levels, and echocardiograms were not significantly different when Tyvaso was administered via tracheostomy compared with oral administration. This case report summarises the method used to deliver Tyvaso via a tracheostomy tube, which proved to be successful in this patient. PMID- 26370631 TI - Amoxicillin-associated rash in glandular fever. PMID- 26370632 TI - Bilateral sudden sensorineural hearing loss in Staphylococcus aureus endocarditis. AB - This case highlights the diagnostic challenges in patients presenting with bilateral sudden sensorinueral hearing loss (SNHL). The aetiology of bilateral sudden SNHL may span several medical disciplines. Therefore, clinicians should be mindful of such presentations, and consider aetiologies beyond otological and neurological causes. We present a case of a previously healthy 51-year-old woman who presented with coryzal symptoms and sudden audiovestibular failure. Examination revealed fever, tachycardia, bilateral profound hearing loss and nystagmus. Following investigations, an initial working diagnosis of vasculitis was made. Later, blood cultures revealed methicillin-sensitive Staphylococcus aureus (MSSA) and a transoesophageal echocardiogram confirmed endocarditis. The patient made a good recovery, but the hearing loss was permanent and managed with a cochlear implant. PMID- 26370633 TI - Oesophageal stent-associated esophagorespiratory fistula. PMID- 26370634 TI - An atypical case of chronic diarrhoea: olmesartan-induced sprue-like enteropathy. AB - Olmesartan use has been associated with chronic diarrhoea and weight loss due to severe sprue-like enteropathy, yet this is still not well known among clinicians. We present the unique case of an 84-year-old Filipino woman diagnosed with olmesartan-induced sprue-like enteropathy after an extensive work up for chronic diarrhoea, and without improvement despite multiple empiric treatments for nearly 15 months. Withdrawal of olmesartan resulted in clinical and histological improvement. This case provides further evidence for olmesartan-induced sprue like enteropathy, and emphasises the importance of its awareness and recognition among gastroenterologists and primary care physicians alike. PMID- 26370635 TI - Surgical stabilisation in a 13-year-old boy with traumatic flail chest. AB - Flail chest after blunt trauma to the chest has a high morbidity and mortality rate. Traumatic flail chest in children rarely occurs due to flexibility of the ribcage. We describe the case of a 13-year-old boy sustaining a flail chest after a high-energy trauma. Conservative treatment with proper mechanical ventilation and pain management was unsuccessful, and was followed by operative rib fixation. The patient was discharged home 17 days after surgery and, at 4 months follow-up, had fully recovered. This case report shows the possibility of operative rib fixation as treatment for flail chest in children. PMID- 26370637 TI - Erratum. PMID- 26370636 TI - Postnatal diagnosis of maternal congenital heart disease: missed opportunities. AB - A 30-year-old primigravida with no known comorbidities presented to the emergency department at 29+6/40 gestation, with breathlessness. The initial diagnosis was pulmonary embolism, which was later revised following initial investigations and considered to be pre-eclampsia/HELLP (haemolysis, elevated liver enzymes, low platelets) syndrome. Following caesarean section and delivery of a live baby, the patient had episodes of cyanotic hypoxia and was admitted to intensive care. A provisional diagnosis of idiopathic pulmonary hypertension was performed. Decompensation led to transfer to a specialist intensive care unit for extracorporeal membrane oxygenation, where a diagnosis of patent ductus arteriosus and Eisenmenger's syndrome was made. Heart disease is the leading indirect cause of maternal death, and Eisenmenger's syndrome in pregnancy carries a 50-65% mortality. A literature review demonstrated that this is the only reported case of a postnatal diagnosis of Eisenmenger's syndrome. We considered missed opportunities to make an earlier diagnosis, so that patients and doctors will benefit from the lessons we learnt. PMID- 26370638 TI - Heroin overdose resuscitation with naloxone: patient uses own prescribed supply to save the life of a peer. AB - Opiate overdose is the primary cause of death among injection-drug users, representing a major public health concern worldwide. Opiate overdose can be reversed through timely administration of naloxone, and users have expressed willingness to carry the antidote for emergency use (take-home naloxone). In November 2014, new WHO guidelines identified that naloxone should be made available to anyone at risk of witnessing an overdose. We present the case of a 46-year-old man in opioid-maintenance treatment who used take-home naloxone to rescue an overdose victim. This is the first- ever account of a patient using dose titration of naloxone to restore respiratory function while minimising the risk of adverse effects. To improve the safety of take-home naloxone, the authors call for clinicians involved in the treatment of opiate users to: prescribe take home naloxone to all patients; forewarn patients of potential side effects; and instruct patients in naloxone dose titration. PMID- 26370639 TI - Normal and aging hair biology and structure 'aging and hair'. AB - Much like an individual's hairstyle, hair fibers along the scalp see a number of changes over the course of one's lifetime. As the decades pass, the shine and volume synonymous with youthful hair may give way to thin, dull, and brittle hair commonly associated with aging. These changes are a result of a compilation of genetic and environmental elements influencing the cells of the hair follicle, specifically the hair follicle stem cells and melanocytes. Telomere shortening, decrease in cell numbers, and particular transcription factors have all been implicated in this process. In turn, these molecular alterations lead to structural modifications of the hair fiber, decrease in melanin production, and lengthening of the telogen phase of the hair cycle. Despite this inevitable progression with aging, there exists an array of treatments such as light therapy, minoxidil, and finasteride which have been designed to mitigate the effects of aging, particularly balding and thinning hair. Although each works through a different mechanism, all aim to maintain or potentially restore the youthful quality of hair. PMID- 26370640 TI - Evaluation of hair loss. AB - The evaluation of a patient with hair problems is a fundamental step for the correct diagnosis of disease, as it gives important information and helps in choosing the diagnostic tools that should be utilized to confirm the clinical suspicion. The evaluation includes a clinical history and patient examination and is followed by invasive and noninvasive tests. Often, the sole clinical examination permits the correct diagnosis of the hair disease and the evaluation of its severity and progression. For this reason, time should be spent to get all of the necessary anamnestic data and to carefully examine the patient. Dermoscopy (trichoscopy) will afterward add additional data that can be further increased by scalp biopsy for histopathology and/or by other more specific tests. When approaching a patient with hair problems, it is mandatory to consider the strong psychological impact of hair diseases, which are very often associated with severe emotional distress. For this reason, patients should be managed with care by spending time listening to their complaints and by explaining in detail their disease and its possible treatments. The patient will only be able to properly adhere to treatment and to obtain the best result if she/he understands her/his hair problem and its possible solutions. PMID- 26370641 TI - Scalp dermoscopy or trichoscopy. AB - Scalp dermoscopy or 'trichoscopy' represents a valuable, noninvasive technique for the evaluation of patients with hair loss that allows for magnified visualization of the hair and scalp skin. It may be performed with a manual dermoscope (*10 magnification) or a videodermoscope (up to *1,000 magnification). In particular, trichoscopy enhances the diagnosis of androgenetic alopecia, alopecia areata, telogen effluvium, trichotillomania, congenital triangular alopecia, scarring alopecia, tinea capitis and hair shaft disorders. This method is simple, quick and easy to perform, reduces the need for scalp biopsy, is well accepted by patients, and is useful for monitoring treatment and follow-up. PMID- 26370642 TI - Androgenetic, diffuse and senescent alopecia in men: practical evaluation and management. AB - Male baldness is the most common diagnosis in men that present with hair loss. It is a genetically determined condition that is clearly an androgen-dependent trait, mainly driven by dihydrotestosterone action on the hair follicles, leading to miniaturization. Although in general this condition is socially accepted as a natural process in a man's life, for some individuals it might significantly impact quality of life, reducing self-esteem and increasing stress. This chapter encompasses the most important aspects of the practical evaluation (clinical features, trichoscopy, trichogram, histopathology, relevant blood tests) and management of male baldness, diffuse baldness and senescent alopecia. PMID- 26370643 TI - Female pattern hair loss. AB - Female pattern hair loss, or female pattern androgenetic alopecia, is a nonscarring alopecia with a multi-factorial etiology that mostly affects postmenopausal women and is characterized by a reduction in hair density over the crown and frontal scalp. The clinical picture is characterized by a diffuse rarefaction of scalp hair over the mid-frontal scalp and a more-or-less intact frontal hairline without any signs of inflammation or scarring. Although the disease poses only a cosmetic concern, it is chronic and may have a significant negative psychological impact on the affected person. The aim of treating female pattern hair loss is to reduce hair loss and, to a certain extent, succeed in promoting hair regrowth. Various treatment methods are available, but it remains unclear which are the most effective. Early initiation of treatment and the combination of various modalities seem to be more efficacious than monotherapy. PMID- 26370644 TI - Hair loss in children. AB - Hair diseases represent frequent complaints in dermatology clinics, and they can be caused by a number of conditions reflected by specific diagnoses. Hair loss is not uncommon in the pediatric group, but its patterns in this group are different from those seen in adults. Additionally, in children, these disorders can have psychological effects that can interfere with growth and development. Hair is easily accessible for examination, and dermatologists are in the enviable situation of being able to study many disorders using simple diagnostic techniques. To fully understand hair loss during childhood, a basic comprehension of normal hair growth is necessary. Knowledge of the normal range and variation observed in the hair of children further enhances its assessment. This chapter has been written in an attempt to facilitate the diagnostic process during daily practice by helping to distinguish between acquired and congenital hair diseases. It can sometimes be difficult to differentiate between abnormality and normality in neonatal hair aspects. Management of hair disorders can be quite a daunting task for the attending physician and mandates a holistic approach to the patient. Some hair disturbances have no effective treatment, and for others, no single treatment is 100% successful. If no effective treatment for a hair loss disease exists, a cosmetic approach is important. PMID- 26370645 TI - Alopecia areata. AB - Alopecia areata (AA) is a common, non-scarring alopecia that usually presents as well-circumscribed patches of sudden hair loss and affects 0.1-0.2% of the population. The aetiology of AA is thought to be both genetic and autoimmune in nature. One hundred and thirty-nine single nucleotide polymorphisms linked to AA have been identified in 8 regions of the genome and have been found to be associated with T cells or the hair follicle. Furthermore, patients with AA have been found to have an increased frequency of hair follicle-specific auto antibodies. The diagnosis of AA is usually made on clinical grounds, and further investigations are not usually needed. Intralesional corticosteroids remain the treatment of choice. Systemic steroids are also highly effective; however, side effects make them less desirable to both patients and physicians. Other available treatment options include anthralin, minoxidil, topical immunotherapy and systemic immunosuppressants. These treatments will be discussed in depth in this chapter. The morbidity of AA is largely psychological; therefore, the successful treatment of AA should include focusing on improving the psychological impact of this condition. PMID- 26370646 TI - Primary scarring alopecias. AB - Scarring alopecia or cicatricial alopecia results from follicular damage that is sufficient to cause the destruction and replacement of pilosebaceous structures by scar tissue. Primary scarring alopecias represent a group of disorders that primarily affect the hair follicles, as opposed to secondary scarring alopecias, which affect the dermis and secondarily cause follicular destruction. Inflammation may predominantly involve lymphocytes or neutrophils. Cicatricial alopecias that mainly involve lymphocytic inflammation include discoid lupus erythematosus, lichen planopilaris, frontal fibrosing alopecia, central centrifugal alopecia, and pseudopelade (Brocq). Cicatricial alopecias that are due to predominantly neutrophilic inflammation include folliculitis decalvans, tufted folliculitis, and dissecting cellulitis of the scalp. Folliculitis keloidalis is a cicatricial alopecia with a mixed inflammatory infiltrate. PMID- 26370647 TI - Molecular genetics of alopecias. AB - Recent developments in research methods and techniques, such as whole-exome and genome sequencing, have substantially improved our understanding of genetic conditions. Special progress has been made in the field of genotrichoses, or hereditary hair diseases, a field that has been obscure for many years. The underlying genes for many of the monogenic hair diseases are now known. Additionally, complex analyses of large cohorts of patients have given us the first clues to the genes associated with polygenic hair disorders, such as androgenetic alopecia and alopecia areata. Thanks to these major findings, the sophisticated regulation of the morphogenesis, development and growth of hair follicles has begun to be revealed, and new players in this delicate molecular interplay have been exposed. PMID- 26370648 TI - Alopecias due to drugs and other skin and systemic disorders. AB - In this chapter, we will discuss the most common alopecias due to drugs and other skin and systemic disorders. The following hair disorders will be analyzed: telogen effluvium (acute and chronic); anagen effluvium; folliculotropic mycosis fungoides; and folliculitis due to bacteria, fungi, parasites, human immunodeficiency virus disease, lupus erythematosus, and sarcoidosis. We will cover topics including the epidemiology, etiology, clinical picture, and diagnosis of and current treatments for each disease. PMID- 26370649 TI - Effect of ultraviolet radiation, smoking and nutrition on hair. AB - Similar to the rest of the skin, the hair is exposed to noxious environmental factors. While ultraviolet radiation (UVR) and smoking are well appreciated as major factors contributing to the extrinsic aging of the skin, their effects on the condition of hair have only lately attracted the attention of the medical community. Terrestrial solar UVR ranges from approximately 290 to 400 nm; UV-B (290-315 nm) reaches only the upper dermis, while the penetration of UV-A (315 400 nm) into the dermis increases with wavelength. The two most important chronic effects of UVR on the skin and bald scalp are photocarcinogenesis and solar elastosis; however, the effects of UVR on hair have largely been ignored. As a consequence of increased leisure time and a growing popularity of outdoor activities and holidays in the sun, the awareness of sun protection of the skin has become important and should also apply to the hair. Besides being the single most preventable cause of significant cardiovascular and pulmonary morbidity and an important cause of death, the association of tobacco smoking with various adverse effects on the skin and hair has also been recognized. Increasing public awareness of the association between smoking and hair loss seems to offer a good opportunity for the prevention or cessation of smoking, since the appearance of hair plays an important role in the overall physical appearance and self perception of people. Finally, the quantity and quality of hair are closely related to the nutritional state of an individual. Normal supply, uptake, and transport of proteins, calories, trace elements, and vitamins are of fundamental importance in tissues with high biosynthetic activity, such as the hair follicle. In instances of protein and calorie malnutrition as well as essential amino acid, trace element, and vitamin deficiencies, hair growth and pigmentation may be impaired. Ultimately, important commercial interest lies in the question of whether increasing the content of an already adequate diet with specific amino acids, vitamins and/or trace elements may further promote hair growth. Unless the hair is impaired due to nutritional deficiency, there is only so much that nutrients can do to increase the size of individual hairs because hair thickness is largely genetic. Nevertheless, there are external factors that influence hair health to such a degree that micronutrients could boost hair that is suffering from these problems. PMID- 26370650 TI - Hair care and dyeing. AB - Alopecia can be effectively camouflaged or worsened through the use of hair care techniques and dyeing. Proper hair care, involving hair styling and the use of mild shampoos and body-building conditioners, can amplify thinning scalp hair; however, chemical processing, including hair dyeing, permanent waving, and hair straightening, can encourage further hair loss through breakage. Many patients suffering from alopecia attempt to improve their hair through extensive manipulation, which only increases problems. Frequent haircuts to minimize split ends, accompanied by gentle handling of the fragile fibers, is best. This chapter offers the dermatologist insight into hair care recommendations for the alopecia patient. PMID- 26370651 TI - Age-related hair pigment loss. AB - Humans are social animals that communicate disproportionately via potent genetic signals imbued in the skin and hair, including racial, ethnic, health, gender, and age status. For the vast majority of us, age-related hair pigment loss becomes the inescapable signal of our disappearing youth. The hair follicle (HF) pigmentary unit is a wonderful tissue for studying mechanisms generally regulating aging, often before this becomes evident elsewhere in the body. Given that follicular melanocytes (unlike those in the epidermis) are regulated by the hair growth cycle, this cycle is likely to impact the process of aging in the HF pigmentary unit. The formal identification of melanocyte stem cells in the mouse skin has spurred a flurry of reports on the potential involvement of melanocyte stem cell depletion in hair graying (i.e., canities). Caution is recommended, however, against simple extrapolation of murine data to humans. Regardless, hair graying in both species is likely to involve an age-related imbalance in the tissue's oxidative stress handling that will impact not only melanogenesis but also melanocyte stem cell and melanocyte homeostasis and survival. There is some emerging evidence that the HF pigmentary unit may have regenerative potential, even after it has begun to produce white hair fibers. It may therefore be feasible to develop strategies to modulate some aging-associated changes to maintain melanin production for longer. PMID- 26370652 TI - Ethnic hair disorders. AB - The management of hair and scalp conditions is difficult in any patient, especially given the emotional and psychological implications of hair loss. This undertaking becomes even more challenging in the ethnic patient. Differences in hair care practices, hair shaft morphology, and follicular architecture add complexity to the task. It is imperative that the physician be knowledgeable about these practices and the phenotypic differences seen in ethnic hair in order to appropriately diagnose and treat these patients. In this chapter, we will discuss cultural practices and morphologic differences and explain how these relate to the specific disorders seen in ethnic populations. We will also review the most prominent of the ethnic hair conditions including acquired trichorrhexis nodosa, traction alopecia, central centrifugal cicatricial alopecia, pseudofolliculitis barbae, dissecting cellulitis, and acne keloidalis nuchae. PMID- 26370653 TI - Advances in hair transplantation: longitudinal partial follicular unit transplantation. AB - There are different techniques of hair transplantation. The most common and known hair transplantation methods are the 'strip' method, where a strip of skin containing hair follicles is removed, cut into grafts and implanted in the recipient area, and the follicle unit extraction (FUE) method, in which whole follicle units are extracted one by one and implanted one by one back into the recipient area. The FUE method is more patient friendly and leaves only tiny scars compared to the strip method, which leaves visible linear scars at the donor area. Both methods, however, have the major disadvantage that the extracted hair follicles are removed and the availability of donor hair follicles are limited and results in a decrease in hair density, as no re-grow will occur in the donor area. Since partial longitudinal-follicular unit transplantation (PL FUT) extracts partial longitudinal follicular units that can be used as complete follicular units to regenerate completely differentiated hair growth and the partial follicular units that remain in the dermis in the donor area can survive and produce hair, PL-FUT enables us to multiply hair follicles in vivo while preserving the donor area. Although this technique is suitable for androgenic alopecia, PL-FUT could also be suitable in persons who have a relative small donor area compared to the recipient area like burn victims, as well as scarring alopecia's like frontal fibrosing alopecia. PMID- 26370656 TI - Postprandial effects of a polyphenolic grape extract (PGE) supplement on appetite and food intake: a randomised dose-comparison trial. AB - BACKGROUND: There is recent evidence that glucose delivered to the distal small intestine (SI) may stimulate the ileal brake and inhibit appetite. High polyphenolic grape extract (PGE) has been shown to inhibit alpha-amylase and alpha-glucosidase activity, two key enzymes required for starch digestion, in vitro. It is hypothesised to slow digestion and absorption of starch in the proximal SI such that glucose may be delivered distally into the ileum and suppress appetite. This study investigated the safety and efficacy of a PGE supplement, delivered within a capsule and consumed with a high-starch breakfast, on appetite ratings and ad libitum energy intake (EI) at a subsequent lunch meal. METHODS: Twenty healthy, non-obese (BMI 18-28 kg/m(2)) male volunteers participated in a randomised, double blind, placebo controlled, three arm, cross over study. Participants were administered (i) low dose PGE500 (500 mg), (ii) high dose PGE1500 (1500 mg), and (iii) matched placebo with a 2 MJ high-starch breakfast (white bread); followed 3 h later by a single item buffet-style lunch meal (pasta and meat sauce). Outcome variables were feelings of hunger, fullness, prospective thoughts of food (TOF) and satisfaction assessed using visual analogue scales (VAS); and ad lib energy and macronutrient intake at the lunch meal. RESULTS: There was no detectable effect of PGE500 or PGE1500 compared with placebo (all, time*supplement interaction, P > 0.05) on VAS-assessed hunger, fullness, TOF or satisfaction. There was also no evidence that PGE significantly altered ad lib energy or macronutrient intake at the lunch meal relative to placebo (P > 0.05). EI following PGE500 was +164 kJ higher than placebo (+5.3%, P > 0.05); and EI following PGE1500 was -51 kJ lower than placebo (-1.7%, P > 0.05). CONCLUSIONS: Whilst well tolerated, there was no evidence that encapsulated low dose PGE500 or high dose PGE1500 consumed with a high starch breakfast meal altered postprandial hunger, fullness, TOF or satisfaction relative to a matched placebo. Nor was there evidence that either dose altered ad lib energy or macronutrient intake at an outcome meal. TRIAL REGISTRATION: ACTRN12614000041651. PMID- 26370657 TI - Ambient Particulate Matter Air Pollution Exposure and Mortality in the NIH-AARP Diet and Health Cohort. AB - BACKGROUND: Outdoor fine particulate matter (<= 2.5 MUm; PM2.5) has been identified as a global health threat, but the number of large U.S. prospective cohort studies with individual participant data remains limited, especially at lower recent exposures. OBJECTIVES: We aimed to test the relationship between long-term exposure PM2.5 and death risk from all nonaccidental causes, cardiovascular (CVD), and respiratory diseases in 517,041 men and women enrolled in the National Institutes of Health-AARP cohort. METHODS: Individual participant data were linked with residence PM2.5 exposure estimates across the continental United States for a 2000-2009 follow-up period when matching census tract-level PM2.5 exposure data were available. Participants enrolled ranged from 50 to 71 years of age, residing in six U.S. states and two cities. Cox proportional hazard models yielded hazard ratio (HR) estimates per 10 MUg/m3 of PM2.5 exposure. RESULTS: PM2.5 exposure was significantly associated with total mortality (HR = 1.03; 95% CI: 1.00, 1.05) and CVD mortality (HR = 1.10; 95% CI: 1.05, 1.15), but the association with respiratory mortality was not statistically significant (HR = 1.05; 95% CI: 0.98, 1.13). A significant association was found with respiratory mortality only among never smokers (HR = 1.27; 95% CI: 1.03, 1.56). Associations with 10-MUg/m3 PM2.5 exposures in yearly participant residential annual mean, or in metropolitan area-wide mean, were consistent with baseline exposure model results. Associations with PM2.5 were similar when adjusted for ozone exposures. Analyses of California residents alone also yielded statistically significant PM2.5 mortality HRs for total and CVD mortality. CONCLUSIONS: Long-term exposure to PM2.5 air pollution was associated with an increased risk of total and CVD mortality, providing an independent test of the PM2.5-mortality relationship in a new large U.S. prospective cohort experiencing lower post-2000 PM2.5 exposure levels. CITATION: Thurston GD, Ahn J, Cromar KR, Shao Y, Reynolds HR, Jerrett M, Lim CC, Shanley R, Park Y, Hayes RB. 2016. Ambient particulate matter air pollution exposure and mortality in the NIH-AARP Diet and Health cohort. Environ Health Perspect 124:484-490; http://dx.doi.org/10.1289/ehp.1509676. PMID- 26370658 TI - Templated Growth of Surface Enhanced Raman Scattering-Active Branched Gold Nanoparticles within Radial Mesoporous Silica Shells. AB - Noble metal nanoparticles are widely used as probes or substrates for surface enhanced Raman scattering (SERS), due to their characteristic plasmon resonances in the visible and near-IR spectral ranges. Aiming at obtaining a versatile system with high SERS performance, we developed the synthesis of quasi monodisperse, nonaggregated gold nanoparticles protected by radial mesoporous silica shells. The radial mesoporous channels were used as templates for the growth of gold tips branching out from the cores, thereby improving the plasmonic performance of the particles while favoring the localization of analyte molecules at high electric field regions: close to the tips, inside the pores. The method, which additionally provides control over tip length, was successfully applied to gold nanoparticles with various shapes, leading to materials with highly efficient SERS performance. The obtained nanoparticles are stable in ethanol and water upon thermal consolidation and can be safely stored as a powder. PMID- 26370659 TI - Prevalence of contact allergy in the general population in different European regions. AB - BACKGROUND: Population-based studies about contact allergy are scarce. OBJECTIVES: To obtain reliable estimates of the prevalence of contact allergy in the general population in Europe. METHODS: A cross-sectional study of a random sample from the general population, aged 18-74 years, in five different European countries (Sweden, the Netherlands, Germany, Italy and Portugal). In total, 12 377 subjects were interviewed and a random sample (n = 3119) patch tested to TRUE Test panels 1-3 and Fragrance Mix (FM) II, hydroxyisohexyl 3-cyclohexene carboxaldehyde (HICC) and sesquiterpene lactone mix. A positive patch test reaction is considered as contact allergy. RESULTS: In total, 27.0% [95% confidence interval (CI) 25.5-28.5] had at least one positive reaction to an allergen of the European baseline series, with a significantly higher prevalence in women than in men. The highest age-standardized prevalences (>= 1%) were found for nickel (14.5%, 95% CI 13.2-15.8), thiomersal (5.0%, 95% CI 4.2-5.8), cobalt (2.2%, 95% CI 1.7-2.7), FM II (1.9%, 95% CI 1.5-2.5), FM I (1.8%, 95% CI 1.4 2.3), HICC (1.4%, 95% CI 1.0-1.9), p-tert-butylphenol formaldehyde resin (1.3%, 95% CI 0.9-1.7) and para-phenylenediamine (1.0%, 95% CI 0.6-1.3). Only nickel and thiomersal showed a statistically significantly different prevalence for contact allergy among the different European populations. Subjects reporting contact dermatitis in their lifetime (age-standardized prevalence 15.1%, 95% CI 13.8 16.3) had an increased risk for contact allergy (odds ratio 1.9, 95% CI 1.5-2.5). The risk of having a contact allergy was not increased in those with atopic dermatitis (prevalence 7.6%, 95% CI 6.7-8.6; odds ratio 1.0, 95% CI 0.7-1.4). CONCLUSIONS: Contact allergy to at least one allergen of the European baseline series was diagnosed in more than one-quarter of the general European population. Therefore measures to improve the primary prevention of contact allergy have to be enforced. PMID- 26370660 TI - Voxel-based morphometry study on monozygotic twins discordant for Alzheimer's disease. AB - OBJECTIVES: We set to investigate the possible role of genes and environment in developing Alzheimer's disease (AD) in monozygotic twin pairs discordant for AD. METHODS: Three pairs of twins discordant for AD, who were enrolled in the Finnish Twin Cohort, were used in the study and compared with 13 controls. Gray matter changes were assessed with magnetic resonance images using voxel-based morphometry with statistical parametric mapping. RESULTS: In the affected twins, the peaks of volume loss were located bilaterally in the temporal (including the hippocampus), the frontal, and the parietal lobes, while in the unaffected siblings, the peaks were located in the frontal gyri and in the parietal lobule. Thus, in the unaffected twins, the pattern of volume loss overlaps with the neocortical but not with the medial temporal areas. DISCUSSION: These findings suggest that genetic factors more largely control neocortical regions, whereas environmental factors more strongly affect medial temporal regions. PMID- 26370661 TI - Preclinical epigenetic models for screening epigenetic drugs for schizophrenia. AB - Schizophrenia is an important psychiatric disorder for which effective drugs are available. However, there are problems with current drug therapy of schizophrenia in that some patients do not respond adequately. Moreover, some patients show treatment resistance and some patients show cognitive decline despite treatment. Hence new and effective drugs will be useful for the treatment of this disorder. Since there is increasing evidence that epigenetic mechanisms of gene expression are defective in schizophrenia, drugs that correct epigenetic defects, epigenetic drugs, could be useful in the treatment of this disorder. This paper discusses preclinical epigenetic models for screening epigenetic drugs for schizophrenia. It also discusses how such models could be useful for the discovery and development of such drugs. PMID- 26370662 TI - Residual quadrupole interaction in brain and its effect on quantitative sodium imaging. AB - Sodium MRI is particularly interesting given the key role that sodium ions play in cellular metabolism. To measure concentration, images must be free from contrast unrelated to sodium density. However, spin 3/2 NMR is complicated by more than rapid biexponential signal decay. Residual quadrupole interactions (described by frequency omegaQ) can reduce Mxy development during RF excitation. Three experiments, each performed on the same four healthy volunteers, demonstrate that residual quadrupole interactions are of concern in quantitative sodium imaging of the brain. The first experiment shows a reliable increase in the rate of excitation 'flipping' (1%-6%), particularly in white matter with tracts running superior-inferior (i.e. parallel to B0). Increased flip-rates imply an associated signal loss and are to be expected when omegaQ ~ omega1. The second experiment shows that a prescribed flip-angle decrease from 90 degrees to 20 degrees , with concomitant decrease in TE from 0.25 ms to 0.10 ms and no T1 weighting, results in a 14%-26% saline calibration phantom normalized signal (SN) increase in the white matter regions. The third experiment shows that this (SN) increase is primarily due to a residual quadrupole effect, with a small contribution from T2 weighting. There is an observed deviation from the spin 3/2 biexponential curve, also suggesting omegaQ dephasing. Using simulation to explain the results of all three experiments, a model of brain tissue is hypothesized. It includes one pool (50%) with omegaQ = 0, and another (50%) in which omegaQ has a Gaussian distribution with a standard deviation of 625 Hz. Given the result of the second experiment, it is suggested that the use of reduced flip-angles with large omega1 will provide more accurate measures of sodium concentration than 'standard' methods using 90 degrees pulses. Alternatively, further study of sodium omegaQmay provide a means to explore tissue structure and organization. PMID- 26370663 TI - Calibrated prevalence of infertility in 30- to 49-year-old women according to different approaches: a cross-sectional population-based study. AB - STUDY QUESTION: How does the estimated prevalence of infertility among 30- to 49 year-old women vary when using different approaches to its measurement? SUMMARY ANSWER: The prevalence of women with difficulties in conceiving differed widely according to the measurement approach adopted. WHAT IS KNOWN ALREADY: Establishing the true magnitude of infertility as a public health problem is challenging, given that it is not categorized as a disability or chronic condition and may be largely unreported. The time required to conceive is an increasingly frequent concern among couples of reproductive age. Population-based studies do not consider multiple approaches to infertility measurement in the same sample. STUDY DESIGN, SIZE, DURATION: A face-to-face cross-sectional population-based survey of 443 women aged between 30 and 49 years residing in Huelva, southern Spain, was carried out. The sample size estimation was based on an assumed prevalence of infertility of 19%, a sampling error of +/-4.84 percentage points, a design effect of 1.8 and a 95% confidence level. The information was collected in 2011. PARTICIPANTS/MATERIALS, SETTING, METHODS: Self reported information was gathered on socio-demographic data, pregnancy history, time required to become pregnant and perception of difficulties in becoming pregnant. Eight approaches to the estimation of infertility prevalence were considered: diagnosed infertility, subjective infertility, 1-year infertility, primary infertility, secondary infertility and subfertility based on the time taken to conceive (6, 12 or 24 months). Calibration estimators (indirect estimation techniques) were used to extrapolate the infertility prevalences to the whole of Spain. MAIN RESULTS AND THE ROLE OF CHANCE: The response rate was 61.05%. Among 30- to 49-year-old Spanish women, 1.26% had a clinical diagnosis of infertility, 17.58% did not achieve pregnancy in 1 year (1-year infertility), 8.22% perceived difficulties in procreation (subjective infertility), 6.12% had not succeeded in having biological children (primary infertility) and 11.33% had not been able to have another biological child (secondary infertility). Finally, pregnancy was not achieved within 6, 12 and 24 months of starting to attempt conception in 19.98, 11.21 and 4.36% of women, respectively. These approaches to estimate the prevalence of infertility show similar socio-demographic patterns except for educational level. Calibration adjustments allowed extrapolation of these prevalences to Spain and a reduction of from 3.7 to 90.4% in their variances. LIMITATIONS, REASONS FOR CAUTION: The response rate was moderate but acceptable in comparison to similar studies. We only asked whether the women had practiced intercourse without contraceptive methods for >1 year. Hence, we could only calculate the time for which a couple were trying to become pregnant when the woman became pregnant, and we do not know whether it was longer than 1 year for the women failing to conceive. Future research should avoid this study weakness by gathering quantitative data on the months during which vaginal sexual intercourse was practiced, with no time limit. The only prevalence with a high coefficient of variation was that for diagnosed infertility, and our estimation for this prevalence should be interpreted with caution. WIDER IMPLICATIONS OF THE FINDINGS: Despite major differences according to the approach adopted, the prevalences of infertility estimated in our study are comparable with those obtained in other similar studies. A set of categories to measure infertility including subjective infertility, 1-year infertility and subfertility have been proposed here, which may be useful for cross-disciplinary comparisons of infertility in clinical and population-based studies. These measures may also assist health managers to tailor fertility resources and services to the real needs of the population and provide a more rapid and effective response to couples. Finally, the calibration adjustments (indirect estimation techniques) applied to the infertility prevalences help to maximize their generalization and improve accuracy. This technique may be considered as a model for application in other epidemiological studies. PMID- 26370664 TI - Provision of intrauterine contraception in association with first trimester induced abortion reduces the need of repeat abortion: first-year results of a randomized controlled trial. AB - STUDY QUESTION: Can the need of subsequent abortion be reduced by providing intrauterine contraception as a part of the abortion service? SUMMARY ANSWER: Provision of intrauterine devices (IUDs) in association with first trimester abortion more than halved the incidence of repeat abortion during the first year of follow-up. WHAT IS KNOWN ALREADY: Following abortion, the incidence of subsequent abortion is high, up to 30-40%. In cohort studies, intrauterine contraception has reduced the need of repeat abortion by 60-70%. STUDY DESIGN, SIZE, DURATION: A randomized controlled trial. The main outcome measure was the incidence of subsequent induced abortions during the follow-up. Altogether 751 women seeking first trimester induced abortion were recruited and randomized into two groups. Randomization was accomplished by computer-assisted permuted-block randomization with random block sizes of four to six. The investigators did not participate in randomization, which was done before commencing the study. The participants were recruited between 18 October 2010 and 21 January 2013. PARTICIPANTS, SETTINGS, METHODS: The inclusion criteria were age >=18 years, duration of pregnancy <=12 weeks, accepting intrauterine contraception, residence in Helsinki and signing the informed consent form. Women with contraindications to intrauterine contraception, such as uterine anomaly, acute genital infection or pap-smear change requiring surgical treatment were ineligible to participate.This study was conducted in collaboration between the Department of Obstetrics and Gynaecology, University of Helsinki and Helsinki University Hospital, and Centralized family planning of the City of Helsinki.The intervention group (n = 375) was provided with intrauterine contraception (either the levonorgestrel-releasing intrauterine system or copper-releasing intrauterine device) immediately following surgical abortion (18.1%) or at a follow-up 2-4 weeks after medical abortion (81.9%). Women in the control group were prescribed oral contraceptives and advised to contact their primary healthcare unit for a follow-up visit and further contraceptive services according to national guidelines. The women were followed-up to 28 February 2014 by using the Finnish National Abortion Registry, Helsinki University Hospital electronic database and clinical follow-up visit at 1 year. MAIN RESULTS AND THE ROLE OF CHANCE: The median age of the whole study group was 27 years and 44% had a history of induced abortion(s). During the follow-up year the number of women requesting subsequent abortion was significantly lower in the intervention than in the control group (9/375 [2.4%] versus 20/373 [5.4%], difference -3.0 [95% CI -6.0 to -0.2] percentage points, P = 0.038, according to intention-to-treat analysis and 5/346 [1.4%] versus 20/357 [5.6%], difference -4.2(-7.2 to -1.4) percentage points, P = 0.003, according to per-protocol analysis, respectively). Provision of intrauterine contraception was safe with rate of infection and expulsion similar to those reported previously. LIMITATIONS, REASONS FOR CAUTION: The power calculation was calculated for a 5-year follow-up. However, significant differences between the two groups were already seen after 1 year. The present study was performed in a single clinic, where, ~15% of all abortions in Finland are performed. WIDER IMPLICATIONS OF THE FINDINGS: In order to decrease the need of subsequent abortions, IUDs should be provided at the time of abortion. TRIAL REGISTRATION: The study was registered at www.clinicaltrials.gov (NCT01223521). TRIAL REGISTRATION DATE: 18 October 2010. DATE OF FIRST PATIENT'S ENROLMENT: 18 October 2010. PMID- 26370667 TI - A predictive structural model for bulk metallic glasses. AB - Great progress has been made in understanding the atomic structure of metallic glasses, but there is still no clear connection between atomic structure and glass-forming ability. Here we give new insights into perhaps the most important question in the field of amorphous metals: how can glass-forming ability be predicted from atomic structure? We give a new approach to modelling metallic glass atomic structures by solving three long-standing problems: we discover a new family of structural defects that discourage glass formation; we impose efficient local packing around all atoms simultaneously; and we enforce structural self-consistency. Fewer than a dozen binary structures satisfy these constraints, but extra degrees of freedom in structures with three or more different atom sizes significantly expand the number of relatively stable, 'bulk' metallic glasses. The present work gives a new approach towards achieving the long-sought goal of a predictive capability for bulk metallic glasses. PMID- 26370666 TI - High-density interspecific genetic maps of kiwifruit and the identification of sex-specific markers. AB - Kiwifruit (Actinidia chinensis Planchon) is an important specialty fruit crop that suffers from narrow genetic diversity stemming from recent global commercialization and limited cultivar improvement. Here, we present high-density RAD-seq-based genetic maps using an interspecific F1 cross between Actinidia rufa 'MT570001' and A. chinensis 'Guihai No4'. The A. rufa (maternal) map consists of 2,426 single-nucleotide polymorphism (SNP) markers with a total length of 2,651 cM in 29 linkage groups (LGs) corresponding to the 29 chromosomes. The A. chinensis (paternal) map consists of 4,214 SNP markers over 3,142 cM in 29 LGs. Using these maps, we were able to anchor an additional 440 scaffolds from the kiwifruit draft genome assembly. Kiwifruit is functionally dioecious, which presents unique challenges for breeding and production. Three sex-specific simple sequence repeats (SSR) markers can be used to accurately sex type male and female kiwifruit in breeding programmes. The sex-determination region (SDR) in kiwifruit was narrowed to a 1-Mb subtelomeric region on chromosome 25. Localizing the SDR will expedite the discovery of genes controlling carpel abortion in males and pollen sterility in females. PMID- 26370665 TI - Altered expression of microRNA-451 in eutopic endometrium of baboons (Papio anubis) with endometriosis. AB - STUDY QUESTION: Are microRNAs (miRs) altered in the eutopic endometrium (EuE) of baboons following the induction of endometriosis? SUMMARY ANSWER: Induction of endometriosis causes significant changes in the expression of eight miRs, including miR-451, in the baboon endometrium as early as 3 months following induction of the disease. WHAT IS KNOWN ALREADY: Endometriosis is one of the most common gynecological disorders and causes chronic pelvic pain and infertility in women of reproductive age. Altered expression of miRs has been reported in women and has been suggested to play an important role in the pathophysiology of several gynecological disorders including endometriosis. STUDY DESIGN, SIZE, DURATION: EuE was obtained from the same group of baboons before and 3 months after the induction of endometriosis. The altered expression of miR-451 was validated in the eutopic and ectopic endometrium of additional baboons between 3 and 15 months following disease induction. Timed endometrial biopsies from women with and without endometriosis were also used to validate the expression of miR 451. PARTICIPANTS/MATERIALS, SETTING, METHODS: Total RNA was extracted from EuE samples before and after the induction of endometriosis, and miRNA expression was analyzed using a 8 * 15 K miR microarray. Microarray signal data were preprocessed by AgiMiRna software, and an empirical Bayes model was used to estimate the changes. The present study focused on quantitative RT-PCR validation of the microarray data, specifically on miR-451 and its target genes in both baboons (n = 3) and women [control (n = 7) and endometriosis (n = 19)]. Descriptive and correlative analysis of miR-451 and target gene expression was conducted using in situ hybridization and immunohistochemistry, while functional analysis utilized an in vitro 3' untranslated region (UTR) luciferase assay and overexpression of miR-451 in human endometrial and endometriotic cell lines. MAIN RESULTS AND THE ROLE OF CHANCE: Induction of endometriosis results in the altered expression of miR-451, -141, -29c, -21, -424, -19b, -200a and -181a in the baboon endometrium. In the baboon, induction of endometriosis significantly decreased the expression of miR-451 at 3 months (P < 0.001), which was also associated with increased expression of its target gene YWHAZ (14.3.3zeta). A similar significant (P < 0.0001) decrease in miR-451 expression was observed in women with endometriosis. The 3' UTR luciferase assay confirmed the regulation of YWHAZ expression by miR-451. Furthermore, overexpression of miR-451 in 12Z cells (immortalized human endometriotic epithelial cell line) led to the decreased expression of its target YWHAZ and this was correlated with decreased cell proliferation. LIMITATIONS, REASONS FOR CAUTION: The study focused only on miR 451 and one of its targets, namely YWHAZ. A single miR could target number of genes and a single gene could also be regulated by number of miRs; hence, it is possible that other miRs and their regulated genes may contribute to the pathophysiology of endometriosis. WIDER IMPLICATIONS OF THE FINDINGS: Our data suggest that the presence of ectopic lesions in baboon causes changes in EuE miR expression as early as 3 months postinduction of the disease, and some of these changes may persist throughout the course of the disease. We propose that the marked down-regulation of miR-451 in both baboons and women with endometriosis increases the expression of multiple target genes. Increased expression of one of the target genes, YWHAZ, increases proliferation, likely contributing to the pathophysiology of the disease. PMID- 26370668 TI - Assessment of exposure to sexually explicit materials and factors associated with exposure among preparatory school youths in Hawassa City, Southern Ethiopia: a cross-sectional institution based survey. AB - BACKGROUND: According to the 2007 Ethiopian census, youths aged 15-24 years were more than 15.2 million which contributes to 20.6% of the whole population. These very large and productive groups of the population are exposed to various sexual and reproductive health risks. The aim of this study was to assess exposure to Sexually Explicit Materials (SEM) and factors associated with exposure among preparatory school students in Hawassa city, Southern Ethiopia. METHODOLOGY: A cross-sectional institution based study involving 770 randomly selected youth students of preparatory schools at Hawassa city. Multi stage sampling technique was used to select study subjects. Data was collected using pre-tested and self administered questionnaire. Data was entered by EPI INFO version 3.5.1 and analyzed using SPSS version 20.0 statistical software packages. The result was displayed using descriptive, bivariate and multivariate analysis. Statistical association was done for independent predictors (at p < 0.05). RESULT AND DISCUSSION: About 750 students were participated in this study with a response rate of 97.4%. Among this, about 77.3% of students knew about the presence of SEM and most of the respondents 566(75.5%) were watched SEM films/movies and 554(73.9%) were exposed to SE texts. The overall exposure to SEM in school youths was 579(77.2%). Among the total respondents, about 522(70.4%) claimed as having no open discussion on sexual issues with in their family. Furthermore, About 450 (60.0%) respondents complained for having no sexual and reproductive health education at their school. Male students had faced almost two times higher exposure to SEM than female students (95 % CI: AOR 1.84(C.I = 1.22, 2.78). Students who attended private school were more than two times more likely exposed to SEM than public schools (95 % CI: AOR 2.07(C.I = 1.29, 3.30). Students who drink alcohol and labelled as 'sometimes' were two times more likely exposed to SEM than those who never drink alcohol (95 % CI = AOR 2.33(C.I = 1.26, 4.30). Khat chewers who labelled "rarely", "sometimes" and "often" had shown higher exposure (95 % CI: AOR 3.02(CI = 1.65, 5.52), (95 % CI: AOR 3.40(CI = 1.93, 6.00) and (95 % CI: AOR 2.67(CI = 1.46, 4.86) than those who never chew khat, respectively. Regarding SEM access, school youths with label 'easy access were exposed in odds of six folds than youths of no access (95 % CI: AOR 5.64(C.I = 3.56, 8.9). CONCLUSION: High number of students was exposed to sexually explicit materials. Sex, school type, substance use and access to SEM were observed independent predictors of exposure to SEM. MOTIVATION: The current generation of young people is the healthiest, most educated, and most urbanized in history. However, there still remain some serious concerns. Most people become sexually active during adolescence. Premarital sexual activity is common and is on the rise worldwide. Rates are highest in sub Saharan Africa, where more than half of girls aged 15-19 are sexually experienced. Millions of adolescents are bearing children, in sub-Saharan Africa. More than half of women give birth before age 20. The need for improved health and social services aimed at adolescents, including reproductive health services, is being increasingly recognized throughout the world. Approximately 85 % of world adolescents live in developing countries. Each year, up to 100 million becomes infected with a curable sexually transmitted disease (STI). About 40 % of all new global human immunodeficiency virus (HIV) infections occur among 15-24 year olds; with recent estimates of 7000 infected each day. These health risks are influenced by many interrelated factors, such as expectations concerning early marriage and sexual relationships, access to education and employment, gender inequities, sexual violence, and the influence of mass media and popular culture. Furthermore, many adolescents lack strong stable relationships with parents or other adults whom they can talk to about their reproductive health concerns. Despite these challenges, programs that meet the information and service needs of adolescents can make a real difference. Successful programs help young people develop life-planning skill, respect the needs and concerns of young people, involve communities in their efforts, and provide respectful and confidential clinical services. Accordingly, the government of Ethiopia now works on improving adolescent's health as one part of MDG (Goal VI-halting transmission of HIV/AIDS, STI, and other communicable diseases) with a focus on adolescents, since they are most affected population. This finding, therefore, will benefit the government to partly evaluate the goal achieving through adolescents exposure status to sexually explicit materials and improvement of sexual issues free talk with in school with class mates and their family at home. For that matter, we authors decided to publish this finding in BMC Reproductive Health Journal so that on line access will be easy to all governing bodies that they use to re-plan their strategies for better product of plan. Moreover, Researchers, Practitioners, policy makers, Students, school leaders and professionals will also benefit from this finding for their future researches references, knowledge gain and practice. PMID- 26370670 TI - An Audio/Video Reporting Workflow to Supplement Standardized Radiology Reports. AB - Radiology studies are inherently visual and the information contained within is best conveyed by visual methodology. Advanced reporting software allows the incorporation of annotated key images into text reports, but such features may be less effective compared with in-person consultations. The use of web technology and screen capture software to create retrievable on-demand audio/visual reports has not yet been investigated. This approach may preempt potential curbside consultations while providing referring clinicians with a more engaged imaging service. In this work, we develop and evaluate a video reporting tool that utilizes modern screen capture software and web technology. We hypothesize that referring clinicians would find that recorded on-demand video reports add value to clinical practice, education, and that such technology would be welcome in future practice. A total of 45 case videos were prepared by radiologists for 14 attending and 15 trainee physicians from emergency and internal medicine specialties. Positive survey feedback from referring clinicians about the video reporting system was statistically significant in all areas measured, including video quality, clinical helpfulness, and willingness to use such technology in the future. Trainees unanimously found educational value in video reporting. These results suggest the potential for video technology to re-establish the radiologist's role as a pivotal member of patient care and integral clinical educator. Future work is needed to streamline these methods in order to minimize work redundancy with traditional text reporting. Additionally, integration with an existing PACS and dictation system will be essential to ensuring ease of use and widespread adoption. PMID- 26370669 TI - Retinal oxygen distribution and the role of neuroglobin. AB - The retina is the tissue layer at the back of the eye that is responsible for light detection. Whilst equipped with a rich supply of oxygen, it has one of the highest oxygen demands of any tissue in the body and, as such, supply and demand are finely balanced. It has been suggested that the protein neuroglobin (Ngb), which is found in high concentrations within the retina, may help to maintain an adequate supply of oxygen via the processes of transport and storage. We construct mathematical models, formulated as systems of reaction-diffusion equations in one-dimension, to test this hypothesis. Numerical simulations show that Ngb may play an important role in oxygen transport, but not in storage. Our models predict that the retina is most susceptible to hypoxia in the regions of the photoreceptor inner segment and inner plexiform layers, where Ngb has the potential to prevent hypoxia and increase oxygen uptake by 30-40 %. Analysis of a simplified model confirms the utility of Ngb in transport and shows that its oxygen affinity ([Formula: see text] value) is near optimal for this process. Lastly, asymptotic analysis enables us to identify conditions under which the piecewise linear and quadratic approximations to the retinal oxygen profile, used in the literature, are valid. PMID- 26370671 TI - Gene expression of thyroid-specific transcription factors may help diagnose thyroid lesions but are not determinants of tumor progression. AB - PURPOSE: The role of thyroid-specific transcription factors in thyroid malignancy is still poorly understood, so we investigate thyroid-specific transcription factors gene expression both in benign and in malignant thyroid nodules, aiming to study a possible clinical utility of these molecules. METHODS: We quantified TTF-1, FOXE1 and PAX8 mRNA levels, relating their expression to diagnostic and prognostic features of thyroid tumors. RNA was extracted from 4 normal thyroid tissues, 101 malignant [99 papillary thyroid carcinomas (PTC) and 2 anaplastic thyroid carcinomas] and 99 benign thyroid lesion tissues [49 goiter and 50 follicular adenomas (FA)]. RESULTS: Levels of mRNA of both FOXE1 (P < 0.0001) and PAX8 (P < 0.0001) genes, but not TTF-1 (P = 0.7056), were higher in benign than in malignant thyroid lesions. FOXE1 was able to identify malignant nodules with 75.8 % sensitivity, 76.1 % specificity, 75.8 % positive predictive value, 76.1 % negative predictive value and 75.9 % accuracy. PAX8 was able to identify malignancy with 60.6 % sensitivity, 81.1 % specificity, 76.9 % positive predictive value, 66.4 % negative predictive value and 70.6 % accuracy. Both FOXE1 and PAX8 gene expression patterns were also able to differentiate FA from the follicular variant of PTC-FVPTC. However, the investigated gene expression was neither associated with any clinical feature of tumor aggressiveness nor associated with recurrence or survival. CONCLUSIONS: We suggest that FOXE1 and PAX8 gene expression patterns may help to diagnose thyroid nodules, identifying malignancy and characterizing follicular-patterned thyroid lesions, but are not determinants of thyroid tumor progression. PMID- 26370673 TI - The American Conference on Pharmacometrics 2015 (ACoP6). PMID- 26370672 TI - Autism Spectrum Disorder Risk in Relation to Maternal Mid-Pregnancy Serum Hormone and Protein Markers from Prenatal Screening in California. AB - We examined prenatal screening markers and offspring autism spectrum disorder (ASD) using California statewide data on singleton births in 1996 and 2002. Second trimester levels of unconjugated estriol (uE3), human chorionic gonadotropin (hCG), and maternal serum alpha-fetoprotein (MSAFP) were compared between mothers of children with ASD (n = 2586) and of non-cases (n = 600,103). Adjusted odds ratios (AOR) were calculated by logistic regression. Lower uE3 (AOR for < 10th percentile vs. 25th-74th percentiles = 1.21, 95 % CI 1.06-1.37), and higher MSAFP (AOR = 1.21, 95 % CI 1.07-1.37 for > 90th percentile) were significantly associated with ASD. A U-shaped relationship was seen for hCG (AOR = 1.16, 95 % CI 1.02-1.32 for < 10th percentile; AOR = 1.19, 95 % CI 1.05-1.36 for > 90th percentile). Our results further support prenatal hormone involvement in ASD risk. PMID- 26370676 TI - Strategies for treatment of dystonia. AB - Treatment of dystonias is generally symptomatic. To produce sufficient therapy effects, therefore, frequently a multimodal and interdisciplinary therapeutic approach becomes necessary, combining botulinum toxin therapy, deep brain stimulation, oral antidystonic drugs, adjuvant drugs and rehabilitation therapy including physiotherapy, occupational therapy, re-training, speech therapy, psychotherapy and sociotherapy. This review presents the recommendations of the IAB-Interdisciplinary Working Group for Movement Disorders Special Task Force on Interdisciplinary Treatment of Dystonia. It reviews the different therapeutic modalities and outlines a strategy to adapt them to the dystonia localisation and severity of the individual patient. Hints to emerging and future therapies will be given. PMID- 26370677 TI - Considerations on Impact Factor and Publications in Molecular Imaging and Biology. PMID- 26370678 TI - Cross-sectional and Test-Retest Characterization of PET with [(18)F]FP-(+)-DTBZ for beta Cell Mass Estimates in Diabetes. AB - PURPOSE: The vesicular monoamine transporter, type 2 (VMAT2) is expressed by insulin producing beta cells and was evaluated as a biomarker of beta cell mass (BCM) by positron emission tomography (PET) with [(18)F]fluoropropyl dihydrotetrabenazine ([(18)F]FP-(+)-DTBZ). PROCEDURES: We evaluated the feasibility of longitudinal pancreatic PET VMAT2 quantification in the pancreas in two studies of healthy controls and patients with type 1 or 2 diabetes. VMAT2 binding potential (BPND) was estimated voxelwise using a reference tissue method in a cross-sectional study, followed by assessment of reproducibility using a test-retest paradigm. Metabolic function was evaluated by stimulated c-peptide measurements. RESULTS: Pancreatic BPND was significantly decreased in patients with type 1 diabetes relative to controls and the test-retest variability was 9.4%. CONCLUSIONS: Pancreatic VMAT2 content is significantly reduced in long-term diabetes patients relative to controls and repeat scans are sufficiently reproducible to suggest the feasibility clinically VMAT2 measurements in longitudinal studies of new onset diabetes. PMID- 26370679 TI - Intrathecal Clonidine Pump Failure Causing Acute Withdrawal Syndrome With 'Stress Induced' Cardiomyopathy. AB - Clonidine is a central alpha(2)-agonist antihypertensive used widely for opioid/alcohol withdrawal, attention deficit hyperactivity disorder and chronic pain management. We describe a case of clonidine withdrawal causing life threatening hypertensive crisis and stress-induced cardiomyopathy. A 47-year-old man with chronic back pain, treated with clonidine for many years via intrathecal pump (550 mcg/24 h), presented following a collapse and complaining of sudden worsening of back pain, severe headache, diaphoresis, nausea and vomiting. A few hours prior to presentation, his subcutaneous pump malfunctioned. On presentation, vital signs included pulse 100 bpm, BP 176/103 mmHg, temperature 37.8 degrees C and O2 saturation 100 % (room air). Acute clonidine withdrawal with hypertensive crisis was suspected. Intravenous clonidine loading dose and a 50 mcg/h infusion were commenced. Five hours later, severe chest pain, dyspnoea, tachycardia, hypoxia, with BP 180/120 mmHg and pulmonary edema ensued. ECG showed sinus tachycardia with no ST elevation. Repeated intravenous clonidine doses were given (25 mcg every 5-10 min), with ongoing clonidine infusion to control blood pressure. Glyceryl trinitrate infusion, positive pressure ventilation and intravenous benzodiazepines were added. Bedside echocardiogram showed stress induced cardiomyopathy pattern. Serum troponin-I was markedly elevated. His coronary angiography showed minor irregularities in the major vessels. Over the next 3 days in the ICU, drug infusions were weaned. Discharge was 12 days later on oral clonidine, metoprolol, perindopril, aspirin and oxycodone-SR. Two months later, his echocardiogram was normal. The intrathecal pump was removed. We report a case of stress-induced cardiomyopathy resulting from the sudden cessation of long-term intrathecal clonidine. This was managed by re-institution of clonidine and targeted organ-specific therapies. PMID- 26370680 TI - Next generation genome sequencing reveals phylogenetic clades with different level of virulence among Salmonella Typhimurium clinical human isolates in Hong Kong. AB - BACKGROUND: Salmonella Typhimurium is frequently isolated from foodborne infection cases in Hong Kong, but the lack of genome sequences has hindered in depth epidemiological and phylogenetic studies. In this study, we sought to reconstruct the phylogenetic relationship and investigate the distribution and mutation patterns of virulence determinants among local S. Typhimurium clinical isolates using their genome sequences. RESULTS: We obtained genome sequences of 20 S. Typhimurium clinical isolates from a local hospital cluster using a 454 GS FLX Titanium sequencing platform. Phylogenetic analysis was performed based on single nucleotide polymorphism positions of the core genome against the reference strain LT2. Antimicrobial susceptibility was determined using minimal inhibitory concentration for five antimicrobial agents and analyses of virulence determinants were performed through referencing to various databases. Through phylogenetic analysis, we revealed two distinct clades of S. Typhimurium isolates and three outliers in Hong Kong, which differ remarkably in antimicrobial susceptibility and presentation and mutations of virulence determinants. The local isolates were not closely related to many of the previously sequenced S. Typhimurium isolates, except LT2. As the isolates in the two clades spanned over 10 years of isolation, they probably represent endemic strains. The outliers are possibly introduced from outside of Hong Kong. The close relatedness of members in one of the clades to LT2 and the Japanese stool isolate T000240 suggests the potential reemergence of LT2 progeny in regions nearby. CONCLUSIONS: Our study demonstrated the utility of next-generation sequencing coupled to traditional microbiological testing method in a retrospective epidemiological study involving multiple clinical isolates. The evolution of multidrug- and ciprofloxacin resistant strains among the more virulent clade is also an increasing concern. PMID- 26370681 TI - OUTCOME OF CLIVAL CHORDOMAS AFTER SKULL BASE SURGERIES WITH MEAN FOLLOW-UP OF 10 YEARS. AB - BACKGROUND AND OBJECTIVE: Skull base chordomas are clinically malignant because of the difficulty of total removal, high recurrence rate, and occasional drop metastasis. Although aggressive surgical resection and postoperative radiation have been recommended, the long-term outcome remains unsatisfactory. METHODS: From 1992 to 2011, we treated 24 patients with skull base chordoma using aggressive surgical removal as a principal strategy. Skull base approaches were selected according to tumor extension to remove the tumor and surrounding bone as completely as possible. After surgery, all patients were closely observed with MRI to find small and localized recurrent tumors, which were treated with gamma knife radiosurgery or surgical resection. The mean postoperative follow-up duration was 10.2 years (range, 1-17.2 years). RESULTS: The 5-, 10-, and 15-year overall survival rates were 86%, 72%, and 72%, respectively. The 5- and 10-year progression-free survival rates were 47% and 35%, respectively. Tumor extension to the brainstem and partial tumor removal were the factors related to poor survival. CONCLUSIONS: Our results suggest that aggressive surgical removal improves the long-term outcome of patients with skull base chordoma. We would like to emphasize that skull base chordomas should be aggressively removed using various skull base approaches. PMID- 26370682 TI - OVEREXPRESSION OF BOTH CLOCK AND BMAL1 INHIBITS ENTRY TO S PHASE IN HUMAN COLON CANCER CELLS. AB - Many physiological, biochemical and behavioral processes operate under the circadian rhythm, which is generated by an internal time-keeping mechanism commonly referred to as the biological clock, in almost all organisms from bacteria to mammals. The core circadian oscillator is composed of an autoregulatory transcription-translation feedback loop, in which CLOCK and BMAL1 are positive regulators. A cell has two mechanisms, "cell cycle" and "cell rhythm", the relationship between which remains controversial. Therefore, the aim of this study was to explore the effect of Clock and Bmal1 on cell cycle, especially on the G1 phase, using vectors with the tetracycline operator repressor system. The present study revealed that simultaneous induction of Bmal1 and Clock had an influential effect on the cell cycle in SW480/T-REx/Clock/Bmal1 cells, in which both Clock and Bmal1 could be induced by tetracycline. The observation that induction of both Clock and Bmal1 inhibited cell growth and the significant increase of the G1 phase proportion of in SW480/T-REx/Clock/Bmal1 cells indicated that entry from the G1 to S phase was inhibited by the induction of Clock and Bmal1. Furthermore, overexpression of Clock and Bmal1 prevented the cells from entering into the G2/M phase induced by Paclitaxel, and made the cells more resistant to the agent. In conclusion, we found that overexpression of both Clock and Bmal1 suppressed cell growth. In addition, the present study raised the possibility that Clock and Bmal1 may in part play a role in preventing the cells from entering G1 to S phase of cell cycle via suppression of CyclinD1 expression, and thus acquiring resistance to Paclitaxel. PMID- 26370683 TI - MEMBRANE TYPE 1-MATRIX METALLOPROTEINASE (MT1-MMP) IDENTIFIED AS A MULTIFUNCTIONAL REGULATOR OF VASCULAR RESPONSES. AB - Membrane type 1-matrix metalloproteinase (MT1-MMP) functions as a signaling molecules in addition to a transmembrane metalloprotease, which degrades interstitial collagens and extracellular matrix components. This review focuses on the multifunctional roles of MT1-MMP as a signaling molecule in vascular responses to pro-atherosclerotic stimuli in the pathogenesis of cardiovascular diseases. First, the lectin-like oxidized low-density lipoprotein receptor-1 (LOX 1)-MT1-MMP signaling axis contributes to endothelial dysfunction, which is mediated via small GTP-binding protein RhoA and Rac1 activation. Second, MT1-MMP plays a crucial role in reactive oxygen species (ROS) generation through the activation of receptor for advanced glycation end products (AGEs) in smooth muscle cells, indicating that MT1-MMP may be a therapeutic target for diabetic vascular complications. Third, MT1-MMP is involved in RhoA/Rac1 activation and Ca(2+) signaling in the mechanism of thrombin-stimulated endothelial dysfunction and oxidant stress. Fourth, the inhibition of the MT1-MMP/Akt signaling pathway may be an attractive strategy for treating endothelial disordered hemostasis in the development of vascular diseases linked to TNF-alpha-induced inflammation. Fifth, MT1-MMP through RAGE induced RhoA/Rac1 activation and tissue factor protein upregulation through NF-kappaB phosphorylation in endothelial cells stimulated by high-mobility group box-1, which plays a key role in the systemic inflammation. These findings suggest that the MT1-MMP-mediated signaling axis may be a promising target for treating atherosclerosis and subsequent cardiovascular diseases. PMID- 26370685 TI - EFFECT OF CYP2A6*4 GENETIC POLYMORPHISMS ON SMOKING BEHAVIORS AND NICOTINE DEPENDENCE IN A GENERAL POPULATION OF JAPANESE MEN. AB - OBJECTIVES: Nicotine in cigarettes is metabolized primarily by CYP2A6-catalyzed oxidation. The CYP2A6*4 allele, in which CYP2A6 is a homozygous whole-deletion variant, completely lacks enzyme activity. The aim of this study was to examine the effects of CYP2A6*4 genetic polymorphism on smoking behavior and nicotine dependence in a general population of Japanese men. METHODS: The subjects were 124 healthy Japanese men who gave informed consent to give saliva samples. The survey items included general information, smoking behaviors and nicotine dependence. The polymerase chain reaction restriction fragment length polymorphism method was used to analyze the genetic polymorphisms of CYP2A6. The subjects were classified into two groups: Group W (CYP2A6*4 absence: *1A/*1A, *1A/*1B and *1B/*1B) and Group D (CYP2A6*4 presence: *1B/*4A, *4A/*4A, *1A/*4A or *1B/*4D, and *1A/*4D). We analyzed the differences in the survey items between the two groups. RESULTS: There were no significant differences in smoking behaviors between the two groups. However, Group D tended to have less difficulty in refraining from smoking after waking in the morning compared to Group W (p=0.051). CONCLUSIONS: CYP2A6*4 genetic polymorphisms may not strongly affect smoking behavior but may possibly have an effect on nicotine dependence. PMID- 26370684 TI - THE BASIC DATA FOR RESIDENTS AGED 15 YEARS OR YOUNGER WHO RECEIVED A COMPREHENSIVE HEALTH CHECK IN 2011-2012 AS A PART OF THE FUKUSHIMA HEALTH MANAGEMENT SURVEY AFTER THE GREAT EAST JAPAN EARTHQUAKE. AB - AIM: To assist in the long-term health management of residents and evaluate the health impacts after the Tokyo Electric Power Company's Fukushima Daiichi Nuclear Power Plant accident in Fukushima Prefecture, the Fukushima prefectural government decided to implement the Fukushima Health Management Survey. This report describes the results for residents aged 15 years or younger who received health checks and evaluates the data obtained from 2011 and 2012. METHODS: The target group consisted of residents aged 15 years or younger who had lived in the evacuation zone. The health checks were performed on receipt of an application from any of the residents. The checks, which included the measurements of height, weight, blood pressure, biochemical laboratory findings, and peripheral blood findings, were performed as required. RESULTS: 1) A total of 17,934 (64.5%) and 11,780 (43.5%) residents aged 15 years or younger received health checks in 2011 and 2012, respectively. 2) In both years, a number of male and female residents in the 7-15 year age group were found to suffer from obesity, hyperlipidemia, hyperuricemia, or liver dysfunction. Furthermore, pediatric aged 15 years or younger were commonly observed to suffer from hypertension or glucose metabolic abnormalities. 3) A comparison of data from 2012 and 2011 demonstrated that both males and females frequently showed increased body height and decreased body weight in 2012. The prevalence of hypertension, glucose metabolic abnormalities, or high gamma-GTP values in males and females in the 7-15 year age group in 2012 was lower than that in 2011. However, the prevalence of hyperuricemia among residents in the 7-15 year age group was higher in 2012 than in 2011. CONCLUSIONS: These results suggested that some residents aged 15 years or under who had lived in the evacuation zone had developed obesity, hyperlipidemia, hyperuricemia, liver dysfunction, hypertension, or glucose metabolic abnormalities. Therefore, we think that it is necessary to continue the health checks for these residents in order to ameliorate these lifestyle-related diseases. PMID- 26370686 TI - Analysis of Novel Mutations and Methylmalonyl-CoA Mutase Levels in Thai Patients with Isolated Methylmalonic Acidemia. AB - Isolated methylmalonic acidemia (MMA) is an autosomal recessive, inherited disorder that results from either a mut defect of the methylmalonyl-CoA mutase apoenzyme (MCM, the product of the MUT gene) or a cbl defect in the synthesis of its cofactor, adenosylcobalamin (AdoCbl). In this study, biochemical and mutational analyses of three patients clinically diagnosed with MMA were performed. No MCM activity was detected in leukocyte extracts of two patients, while high MCM activity was found in the other, suggesting mut (0) and cbl defects, respectively. A novel (c.IVS6 -3 to -8delCTTTTT, p.K444_L445insFC*) and two known mutations in the MUT gene and one novel (c.227_36delGACCCAAAGA, p.R76Mfs*14) mutation in the MMAB gene were identified. In addition, MCM immunoblot analysis of leukocyte extract samples of these three patients and eight patients previously reported by our group, as well as their parents, showed a good correlation between the MCM protein and activity levels. Patients with mut (0) defective subtypes lacked MCM activity and had no MCM band, while patients carrying the cbl defects had high MCM activity levels and an intense MCM band at about 83 kDa, in comparison to those in their parents. These data expand the mutation spectrum of MMA deficiency. In addition, the examination of MCM protein level may be used as an alternative technique to determine the mut (0) and cbl defective subgroups. PMID- 26370687 TI - A randomized controlled proof-of-concept trial of early sedation management using Responsiveness Index monitoring in mechanically ventilated critically ill patients. AB - INTRODUCTION: Deep sedation is associated with adverse patient outcomes. We recently described a novel sedation-monitoring technology, the Responsiveness Index (RI), which quantifies patient arousal using processed frontal facial EMG data. We explored the potential effectiveness and safety of continuous RI monitoring during early intensive care unit (ICU) care as a nurse decision support tool. METHODS: In a parallel-group controlled single centre proof of concept trial, patients requiring mechanical ventilation and sedation were randomized via sequential sealed envelopes following ICU admission. Control group patients received hourly clinical sedation assessment and daily sedation holds; the RI monitor was connected but data were concealed from clinical staff. The intervention group received control group care, but RI monitoring was visible and nurses were asked to adjust sedation to maintain patients with an RI>20 whenever possible. Traffic-light colour coding (RI<20, Red; 20-40, Amber; >40, Green) simplified decision-making. The intervention lasted up to 48 hours. Sixteen nurses were interviewed to explore their views of the novel technology. RESULTS: We analysed 74 patients treated per protocol (36 intervention; 38 control). The proportion of patients with RI<20 was identical at the start of monitoring (54% both groups). Overall, the proportion of time with RI<20 trended to lower values for the intervention group (median 16% (1-3rd quartile 8-30%) versus 33% (10 54%); P = 0.08); sedation and analgesic use was similar. A post hoc analysis restricted to patients with RI<20 when monitoring started, found intervention patients spent less time with low RI value (16% (11-45%) versus 51% (33-72%); P = 0.02), cumulative propofol use trended to lower values (median 1090 mg versus 2390 mg; P = 0.14), and cumulative alfentanil use was lower (21.2 mg versus 32.3 mg; P = 0.01). RASS scores were similar for both groups. Sedation related adverse event rates were similar (7/36 versus 5/38). Similar proportions of patients had sedation holds (83% versus 87 %) and were extubated (47% versus 44%) during the intervention period. Nurses valued the objective visible data trends and simple colour prompts, and found RI monitoring a useful adjunct to existing practice. CONCLUSIONS: RI monitoring was safe and acceptable. Data suggested potential to modify sedation decision-making. Larger trials are justified to explore effects on patient-centred outcomes. TRIAL REGISTRATION: NCT01361230 (registered April 19, 2010). PMID- 26370688 TI - Antifungal de-escalation was not associated with adverse outcome in critically ill patients treated for invasive candidiasis: post hoc analyses of the AmarCAND2 study data. AB - PURPOSE: Systemic antifungal therapy (SAT) of invasive candidiasis needs to be initiated immediately upon clinical suspicion. Controversies exist about adequate time and potential harm of antifungal de-escalation (DE) in documented and suspected candidiasis in ICU patients. Our objective was to investigate whether de-escalation within 5 days of antifungal initiation is associated with an increase of the 28-day mortality in SAT-treated non-neutropenic adult ICU patients. METHODS: From the 835 non-neutropenic adults recruited in the multicenter prospective observational AmarCAND2 study, we selected the patients receiving systemic antifungal therapy for a documented or suspected invasive candidiasis in the ICU and who were still alive 5 days after SAT initiation. They were included into two groups according to the occurrence of observed SAT de escalation before day 6. The average causal SAT de-escalation effect on 28-day mortality was evaluated by using a double robust estimation. RESULTS: Among the 647 included patients, early de-escalation at day 5 after antifungal initiation occurred in 142 patients (22%), including 48 (34%) patients whose SAT was stopped before day 6. After adjustment for the baseline confounders, early SAT de escalation was the solely factor not associated with increased 28-day mortality (RR 1.12, 95% CI 0.76-1.66). CONCLUSION: In non-neutropenic critically ill adult patients with documented or suspected invasive candidiasis, SAT de-escalation within 5 days was not related to increased day-28 mortality but it was associated with decreased SAT consumption. These results suggest for the first time that SAT de-escalation may be safe in these patients. PMID- 26370689 TI - Risk of type 2 diabetes mellitus in patients with acute critical illness: a population-based cohort study. AB - PURPOSE: This large population-based cohort study evaluated the association between certain critical illnesses and the incidence of newly diagnosed type 2 diabetes mellitus (T2DM) in Taiwan. METHODS: Data were obtained from the Taiwan National Health Insurance Research Database. According to age, sex, and propensity score-matching, a cohort comprising 9528 patients with critical illness, including septicemia, septic shock, acute myocardial infarction (AMI), and stroke, and a control cohort of 9528 patients with no critical illness were identified. Cox proportional-hazard regression and competing-risk regression models were employed to evaluate the risk of developing T2DM. FINDINGS: With the median follow-up periods (interquartile range) of 3.86 (1.64-6.93) and 5.12 (2.51 8.13) years for the patients in the critical illness and control cohorts, respectively, the risk of developing T2DM in the critical illness cohort was significantly higher than in the control cohort (adjusted hazard ratio, aHR = 1.32; 95% confidence interval, CI 1.16-1.50). In the multivariate competing-risk regression models, the aHR of T2DM was 1.58 (95% CI 1.45-1.72) in the critical illness cohort. Moreover, among the patients with these critical illnesses, those with septicemia or septic shock exhibited the highest risk of developing T2DM (aHR = 1.51, 95% CI 1.37-1.67), followed by AMI compared with the control cohort. CONCLUSION: Our results suggest that patients with certain critical illnesses are associated with a high risk of developing T2DM. Clinicians should be aware of this association and intensively screen for T2DM in patients following diagnosis of critical illness. PMID- 26370691 TI - What's new in severe community-acquired pneumonia? Corticosteroids as adjunctive treatment to antibiotics. PMID- 26370692 TI - Effects of gamma radiation on wastewater microbiota. AB - Wastewater treatment by gamma radiation is a promising technology, with the capacity to reduce the impact of chemical and biological pollution of effluents in the environment. The aim of this study was to find out the effect of gamma radiation on the inactivation response of wastewater microorganisms. Wastewater samples were irradiated at a Co-60 facility, at different dose rates and at sublethal doses. The D10-values of total coliforms and mesophilic microbiota were determined for each sample and dose rate. Radio-resistant microorganisms in wastewater samples were isolated and their growth and inactivation kinetics in different composition substrates were determined, to find out the capacity of these bacteria to biodegrade the organic content of the wastewater. The results obtained suggest that irradiation substrate and dose rate influence the response of microorganisms to gamma radiation and could be also important factors for bioremediation. PMID- 26370690 TI - Acute heart failure and cardiogenic shock: a multidisciplinary practical guidance. AB - PURPOSE: Acute heart failure (AHF) causes high burden of mortality, morbidity, and repeated hospitalizations worldwide. This guidance paper describes the tailored treatment approaches of different clinical scenarios of AHF and CS, focusing on the needs of professionals working in intensive care settings. RESULTS: Tissue congestion and hypoperfusion are the two leading mechanisms of end-organ injury and dysfunction, which are associated with worse outcome in AHF. Diagnosis of AHF is based on clinical assessment, measurement of natriuretic peptides, and imaging modalities. Simultaneously, emphasis should be given in rapidly identifying the underlying trigger of AHF and assessing severity of AHF, as well as in recognizing end-organ injuries. Early initiation of effective treatment is associated with superior outcomes. Oxygen, diuretics, and vasodilators are the key therapies for the initial treatment of AHF. In case of respiratory distress, non-invasive ventilation with pressure support should be promptly started. In patients with severe forms of AHF with cardiogenic shock (CS), inotropes are recommended to achieve hemodynamic stability and restore tissue perfusion. In refractory CS, when hemodynamic stabilization is not achieved, the use of mechanical support with assist devices should be considered early, before the development of irreversible end-organ injuries. CONCLUSION: A multidisciplinary approach along the entire patient journey from pre-hospital care to hospital discharge is needed to ensure early recognition, risk stratification, and the benefit of available therapies. Medical management should be planned according to the underlying mechanisms of various clinical scenarios of AHF. PMID- 26370693 TI - Opening our eyes to Global Health; a philosophy of universal values. AB - Globalization is advancing at a pace. As we strive to introduce 'Global Health' into clinical curricula we risk fundamental misunderstandings unless we clearly define what we aim to achieve. Clinicians must be prepared for a life time of uncertainty, change and challenge. The fluctuating world arena will undoubtedly impact on their future work in ways we cannot predict. Population migration, climate change and shifts in cultural dominance are already at play. Global health risks being translated through the eyes of Western ideology as disease based curricula focused paternalistically on 'helping' the developing world. We must not lack humility to open eyes to learning within the context of increasingly diverse environments and patient populations. Global health is as 'local' as it is 'international'. It should be viewed, I argue, as a philosophy based on the values and expectations found within ourselves and our communities. Responding to globalization lies not only in knowledge but embraces human rights, justice and, most importantly, self-awareness. Knowledge is more easily translated into curriculum objectives. We risk letting future clinicians and their patients down if we ignore the other universal values. PMID- 26370694 TI - Image-driven pharmacokinetics: nanomedicine concentration across space and time. AB - Clinical pharmacokinetics (PK) primarily measures the concentration of drugs in the blood. For nanomedicines it may be more relevant to determine concentration within a target tissue. The emerging field of image-driven PK, which utilizes clinically accepted molecular imaging technology, empirically and noninvasively, measures concentration in multiple tissues. Image-driven PK represents the intersection of PK and biodistribution, combining to provide models of concentration across space and time. Image-driven PK can be used both as a research tool and in the clinic. This review explores the history of pharmacokinetics, technologies used in molecular imaging (especially positron emission tomography) and research using image-driven pharmacokinetic analysis. When standardized, image-driven PK may have significant implications in preclinical development as well as clinical optimization of targeted nanomedicines. PMID- 26370695 TI - Targeting memory T cells in type 1 diabetes. AB - Type 1 diabetes (T1D) is a chronic autoimmune disease that leads to progressive destruction of pancreatic beta cells. Compared to healthy controls, a characteristic feature of patients with T1D is the presence of self-reactive T cells with a memory phenotype. These autoreactive memory T cells in both the CD4(+) and CD8(+) compartments are likely to be long-lived, strongly responsive to antigenic stimulation with less dependence on costimulation for activation and clonal expansion, and comparatively resistant to suppression by regulatory T cells (Tregs) or downregulation by immune-modulating agents. Persistence of autoreactive memory T cells likely contributes to the difficulty in preventing disease progression in new-onset T1D and maintaining allogeneic islet transplants by regular immunosuppressive regimens. The majority of immune interventions that have demonstrated some success in preserving beta cell function in the new-onset period have been shown to deplete or modulate memory T cells. Based on these and other considerations, preservation of residual beta cells early after diagnosis or restoration of beta cell mass by use of stem cell or transplantation technology will require a successful strategy to control the autoreactive memory T cell compartment, which could include depletion, inhibition of homeostatic cytokines, induction of hyporesponsiveness, or a combination of these approaches. PMID- 26370696 TI - Sex-specific differential in risk of diabetes-related macrovascular outcomes. AB - Reports from recent studies suggest that diabetes confers a higher risk of cardiovascular disease in women compared to men. Larger studies, including meta analyses, report that women with diabetes have a 44 % greater risk of incident coronary heart disease and a 27 % greater risk of incident stroke compared to men with diabetes. In this article, we summarize results from longitudinal studies that examine sex differences in risk factors for and rates of macrovascular complications from diabetes. We also discuss possible mechanisms for increased cardiovascular risk associated with diabetes in women compared to men, including the clustering of hypertension, obesity, and elevated triglycerides, the possible contribution of hormonal differences, and sex differences in the prescription of and adherence to pharmacologic treatment. In conclusion, diabetes is associated with a slightly higher risk of cardiovascular disease in women compared to men. Future studies should further explore the reasons underlying imperfect use of medications that lower cardiovascular risk in both women and men with diabetes. PMID- 26370697 TI - Can we prevent type 1 diabetes? AB - Type 1 diabetes (T1D) affects 1.93 in 1000 youth in the USA. Over the last 40 years, a combination of genetic and immunological markers has been developed allowing for the accurate prediction of progression to T1D. Despite our abilities to predict disease and the marked improvement in our understanding of the natural history of T1D, therapies capable of preventing or reversing T1D remain elusive. This article will review recent and ongoing efforts to understand the causes of T1D and related efforts to study potential therapies aimed at preventing T1D. PMID- 26370698 TI - Insights from cardiovascular outcome trials with novel antidiabetes agents: what have we learned? An industry perspective. AB - Owing to the close association of cardiovascular (CV) disease with type 2 diabetes and the uncertainty surrounding the CV safety of antidiabetes agents, in 2008 the Food and Drug Administration issued guidance for the demonstration of CV safety for new antidiabetes drugs. Recently the results from CV outcomes trials of three dipeptidyl peptidase-4 (DPP-4) inhibitors and a glucagon-like peptide-1 receptor agonist have been reported. The Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus (SAVOR) trial, the Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care in Patients with Type 2 Diabetes Mellitus and Acute Coronary Syndrome (EXAMINE) trial, and the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) assessed the safety of saxagliptin, alogliptin, and sitagliptin, respectively, in patients with type 2 diabetes with CV disease or at high risk for CV disease. The Evaluation of Lixisenatide in Acute Coronary Syndrome (ELIXA) assessed the safety of lixisenatide in patients with type 2 diabetes and a recent acute coronary syndrome event. The results show that these agents neither increased nor deceased major adverse CV events (CV death, nonfatal myocardial infarction, and nonfatal stroke) compared with placebo. However, the resources needed to conduct these studies may detract from the ability to understand the potential long-term benefit and risk in the majority of patients that are candidates for use of these medications. PMID- 26370700 TI - Mitochondrial dysfunction in diabetic neuropathy: a series of unfortunate metabolic events. AB - Diabetic neuropathy is a dying back neurodegenerative disease of the peripheral nervous system where mitochondrial dysfunction has been implicated as an etiological factor. Diabetes (type 1 or type 2) invokes an elevation of intracellular glucose concentration simultaneously with impaired growth factor support by insulin, and this dual alteration triggers a maladaptation in metabolism of adult sensory neurons. The energy sensing pathway comprising the AMP-activated protein kinase (AMPK)/sirtuin (SIRT)/peroxisome proliferator activated receptor-gamma coactivator alpha (PGC-1alpha) signaling axis is the target of these damaging changes in nutrient levels, e.g., induction of nutrient stress, and loss of insulin-dependent growth factor support and instigates an aberrant metabolic phenotype characterized by a suppression of mitochondrial oxidative phosphorylation and shift to anaerobic glycolysis. There is discussion of how this loss of mitochondrial function and transition to overreliance on glycolysis contributes to the diminishment of collateral sprouting and axon regeneration in diabetic neuropathy in the context of the highly energy-consuming nerve growth cone. PMID- 26370699 TI - New and emerging biomarkers in cardiovascular disease. AB - Cardiovascular disease (CVD) is the most common cause of death and disability worldwide. Therefore, great importance has been placed on the discovery of novel risk factors and metabolic pathways relevant in the prevention and management of CVD. Such research is ongoing and may continue to lead to better risk stratification of individuals and/or the development of new intervention targets and treatment options. This review highlights emerging biomarkers related to lipid metabolism, glycemia, inflammation, and cardiac damage, some of which show promising associations with CVD risk and provide further understanding of the underlying pathophysiology. However, their measurement methodology and assays will require validation and standardization, and it will take time to accumulate evidence of their role in CVD in various population settings in order to fully assess their clinical utility. Several of the novel biomarkers represent intriguing, potentially game-changing targets for therapy. PMID- 26370701 TI - T cell epitopes and post-translationally modified epitopes in type 1 diabetes. AB - Type 1 diabetes (T1D) is an autoimmune disease in which progressive loss of self tolerance, evidenced by accumulation of auto-antibodies and auto-reactive T cells that recognize diverse self-proteins, leads to immune-mediated destruction of pancreatic beta cells and loss of insulin secretion. In this review, we discuss antigens and epitopes in T1D and the role that post-translational modifications play in circumventing tolerance mechanisms and increasing antigenic diversity. Emerging data suggest that, analogous to other autoimmune diseases such as rheumatoid arthritis and celiac disease, enzymatically modified epitopes are preferentially recognized in T1D. Modifying enzymes such as peptidyl deiminases and tissue transglutaminase are activated in response to beta cell stress, providing a mechanistic link between post-translational modification and interactions with the environment. Although studies of such responses in the at risk population have been limited, current data suggests that breakdown in tolerance through post-translational modification represents an important checkpoint in the development of T1D. PMID- 26370704 TI - Erratum to: Arum Palaestinum with isovanillin, linolenic acid and beta-sitosterol inhibits prostate cancer spheroids and reduces the growth rate of prostate tumors in mice. PMID- 26370703 TI - Do tradeoffs structure antibiotic inhibition, resistance, and resource use among soil-borne Streptomyces? AB - BACKGROUND: Tradeoffs among competing traits are believed to be crucial to the maintenance of diversity in complex communities. The production of antibiotics to inhibit competitors and resistance to antibiotic inhibition are two traits hypothesized to be critical to microbial fitness in natural habitats, yet data on costs or tradeoffs associated with these traits are limited. In this work we characterized tradeoffs between antibiotic inhibition or resistance capacities and growth efficiencies or niche widths for a broad collection of Streptomyces from soil. RESULTS: Streptomyces isolates tended to have either very little or very high inhibitory capacity. In contrast, Streptomyces isolates were most commonly resistant to antibiotic inhibition by an intermediate number of other isolates. Streptomyces with either very high antibiotic inhibitory or resistance capacities had less efficient growth and utilized a smaller number of resources for growth (smaller niche width) than those with low inhibition or resistance capacities, suggesting tradeoffs between antibiotic inhibitory or resistance and resource use phenotypes. CONCLUSIONS: This work suggests that life-history tradeoffs may be crucial to the maintenance of the vast diversity of antibiotic inhibitory and resistance phenotypes found among Streptomyces in natural communities. PMID- 26370702 TI - Relationship between CD4 count and quality of life over time among HIV patients in Uganda: a cohort study. AB - BACKGROUND: Immunological markers (CD4 count) are used in developing countries to decide on initiation of antiretroviral therapy and monitor HIV/AIDS disease progression. HIV is an incurable chronic illness, making quality of life paramount. The direct relationship between quality of life and CD4 count is unclear. The purpose of this study is to determine the relationship between change in CD4 count and quality of life measures in a Ugandan cohort of people living with HIV. METHODS: We prospectively assessed quality of life among 1274 HIV patients attending an HIV clinic within a national referral hospital over a period of 6 months. Quality of life was measured using an objective measure, the Medical Outcomes Study HIV health survey summarized as Physical Health Score and Mental Health Score and a subjective measure, the Global Person Generated Index. Generalized estimating equations were used to analyze the data. The primary predictor variable was change in CD4 count, and the outcome was quality of life scores. We controlled for sociodemographic characteristics, clinical factors and behavioral factors. Twenty in-depth interviews were conducted to assess patient perception of quality of life and factors influencing quality of life. RESULTS: Of the 1274 patients enrolled 1159 had CD4 count at baseline and six months and 586 (51%) received antiretroviral therapy. There was no association found between change in CD4 count and quality of life scores at univariate and multivariate analysis among the study participants whether on or not on antiretroviral therapy. Participants perceived quality of life as happiness and well-being, influenced by economic status, psychosocial factors, and health status. CONCLUSIONS: Clinicians and policy makers cannot rely on change in immunological markers to predict quality of life in this era of initiating antiretroviral therapy among relatively healthy patients. In addition to monitoring immunological markers, socioeconomic and psychosocial factors should be underscored in management of HIV patients. PMID- 26370705 TI - Fouling behaviour of membranes with different characteristics by urban wastewater secondary effluent. AB - Fouling behaviours and antifouling properties of polyvinylidene fluoride (PVDF) ultrafiltration membranes blending with polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP) and polymethyl methacrylate (PMMA) had been investigated using the secondary effluent as the filtration medium. The results demonstrated that the antifouling properties of membranes using PVA and PVP as the additives were generally stronger than those using PMMA. Additives PVA and PVP could effectively improve the structural property and hydrophilicity of the membrane and result in an outstanding antifouling property. A dense membrane surface could prevent low molecular foulants from entering into the membrane pores, depositing on the membrane with a loose spongy layer and penetrating into the internal macropore structure. The not fully generated internal macropores on the membrane surface were trend to be plugged, which resulted in serious flux decay and the membrane fouling was irreversible. Filtration cake formed on the membrane due to concentration polarization, which caused membrane flux decline and high flux recovery after cleaning. PMID- 26370706 TI - A dual pH/thermal responsive nanocarrier for combined chemo-thermotherapy based on a copper-doxorubicin complex and gold nanorods. AB - The development of treatment protocols that results in a complete response to chemotherapy has been hampered by low efficacy and systemic toxicity. Here, we created a pH sensitive copper-doxorubicin complex within the core of temperature sensitive liposomes to maintain the stability during blood circulation and trigger Dox release in the tumor site. Synergistically, we also rationally applied gold nanorods (AuNRs) coupled with near-infrared (NIR) field strength to produce a precise and localized temperature, which not only remotely controlled the drug release but also directly destroyed the tumor, to enhance the therapeutic efficacy. As expected, the in vitro release studies showed that the drug release from CuDox-TSLs (Copper ion mediated Doxorubicin loading-Temperature Sensitive Liposomes) was both pH-dependent and temperature-dependent. Furthermore, MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide) assays showed that CuDox-TSLs combined with AuNRs exhibited a closer antiproliferative activity to free Dox in MCF-7 cells. The efficient intracellular Dox release from CuDox-TSLs toward the tumor cells further confirmed the anti-tumor effect. Moreover, the in vivo imaging and biodistribution studies revealed that CuDox-TSLs combined with AuNRs could actively target the tumor site. In addition, the therapeutic studies in MCF-7 nude mice exhibited CuDox-TSLs plus AuNRs in combination with NIR irradiation inhibited tumor growth to a great extent and possessed much lower side effects, which were further confirmed by systemic histological analyses. All detailed evidence suggested a considerable potential of CuDox-TSLs combined with AuNRs for treatment of metastatic cancer. PMID- 26370707 TI - Nanomedicine applied to translational oncology: A future perspective on cancer treatment. AB - The high global incidence of cancer is associated with high rates of mortality and morbidity worldwide. By taking advantage of the properties of matter at the nanoscale, nanomedicine promises to develop innovative drugs with greater efficacy and less side effects than standard therapies. Here, we discuss both clinically available anti-cancer nanomedicines and those en route to future clinical application. The properties, therapeutic value, advantages and limitations of these nanomedicine products are highlighted, with a focus on their increased performance versus conventional molecular anticancer therapies. The main regulatory challenges toward the translation of innovative, clinically effective nanotherapeutics are discussed, with a view to improving current approaches to the clinical management of cancer. Ultimately, it becomes clear that the critical steps for clinical translation of nanotherapeutics require further interdisciplinary and international effort, where the whole stakeholder community is involved from bench to bedside. From the Clinical Editor: Cancer is a leading cause of mortality worldwide and finding a cure remains the holy-grail for many researchers and clinicians. The advance in nanotechnology has enabled novel strategies to develop in terms of cancer diagnosis and therapy. In this concise review article, the authors described current capabilities in this field and outlined comparisons with existing drugs. The difficulties in bringing new drugs to the clinics were also discussed. PMID- 26370709 TI - TRLFS study on the complexation of Cm(III) and Eu(III) with SO3-Ph-BTBP. AB - The complexation of Cm(iii) and Eu(iii) with a water soluble BTBP (sodium 3,3',3'',3'''-([2,2'-bipyridine]-6,6'-diylbis(1,2,4-triazine-3,5,6 triyl))tetrabenzenesulfonate, SO3-Ph-BTBP) is studied using time resolved laser fluorescence spectroscopy. For the complexation of Cm(iii) the influence of the medium (10(-3) M HClO4-> 0.5 M HNO3) is investigated in detail revealing important impacts of the applied medium (pH, ionic strength, anions) on the speciation and conditional stability constants. SO3-Ph-BTBP forms 1 : 2 complexes with Cm(iii) and Eu(iii). The conditional stability constants of [Cm(SO3-Ph BTBP)2](5-) and [Eu(SO3-Ph-BTBP)2](5-) in 0.5 M HNO3 are determined to be log beta02 = 7.3 +/- 0.3 and log beta02 = 5.4 +/- 0.5, respectively. The difference of 1.9 orders of magnitude is in line with hydrophobic BT(B)P type ligands and shows that the selectivity is not affected by tuning the hydrophilicity using SO3 Ph-side chains. PMID- 26370708 TI - Multiscale investigation of USPIO nanoparticles in atherosclerotic plaques and their catabolism and storage in vivo. AB - The storage and catabolism of Ultrasmall SuperParamagnetic Iron Oxide (USPIO) nanoparticles were analyzed through a multiscale approach combining Two Photon Laser Scanning Microscopy (TPLSM) and High-Resolution Transmission Electron Microscopy (HRTEM) at different times after intravenous injection in an atherosclerotic ApoE(-/-) mouse model. The atherosclerotic plaque features and the USPIO heterogeneous biodistribution were revealed down from organ's scale to subcellular level. The biotransformation of the nanoparticle iron oxide (maghemite) core into ferritin, the non-toxic form of iron storage, was demonstrated for the first time ex vivo in atherosclerotic plaques as well as in spleen, the iron storage organ. These results rely on an innovative spatial and structural investigation of USPIO's catabolism in cellular phagolysosomes. This study showed that these nanoparticles were stored as non-toxic iron compounds: maghemite oxide or ferritin, which is promising for MRI detection of atherosclerotic plaques in clinics using these USPIOs. From the Clinical Editor: Advance in nanotechnology has brought new contrast agents for clinical imaging. In this article, the authors investigated the use and biotransformation of Ultrasmall Super-paramagnetic Iron Oxide (USPIO) nanoparticles for analysis of atherosclerotic plagues in Two Photon Laser Scanning Microscopy (TPLSM) and High Resolution Transmission Electron Microscopy (HRTEM). The biophysical data generated from this study could enable the possible use of these nanoparticles for the benefits of clinical patients. PMID- 26370710 TI - The complete mitochondrial genome of a stonefly species, Kamimuria chungnanshana Wu, 1948 (Plecoptera: Perlidae). AB - This study determined the complete mitochondrial (mt) genome of the stonefly, Kamimuria chungnanshana Wu, 1948. The mt genome is 15, 943 bp in size and contains 37 canonical genes which include 22 transfer RNA genes, 13 protein coding genes, and two ribosomal RNA genes, the control region is 1062 bp in length. The phylogenetic tree shows that Kamimuria chungnanshana is sister group of Kamimuria wangi. PMID- 26370712 TI - Pleural Covering Application for Recurrent Pneumothorax in a Patient with Birt Hogg-Dube Syndrome. AB - Birt-Hogg-Dube syndrome (BHDS) is a rare hereditary disease that presents with multiple lung cysts and recurrent pneumothorax. These cysts occupy predominantly the lower-medial zone of the lung field adjacent to the interlobar fissure, and some of them abut peripheral pulmonary vessels. For the surgical management of pneumothorax with BHDS, the conventional approach of resecting all subpleural cysts and bullae is not feasible. Thus, after handling several bullae by using a stapler or performing ligation as a standardized treatment, we applied to a pleural covering technique to thicken the affected visceral pleura and then to prevent recurrence of pneumothorax. We herein report the successful application of a pleural covering technique via thoracoscopic surgery to treat the recurrent pneumothorax of a 30-year-old man with BHDS. This technique is promising for the management of intractable pneumothorax secondary to BHDS. PMID- 26370711 TI - How hepatitis C virus modifies the immunological profile of Sjogren syndrome: analysis of 783 patients. AB - INTRODUCTION: We conducted a study to analyze how infection by hepatitis C virus (HCV) may influence the immunological serum pattern of patients with Sjogren syndrome (SS). METHODS: Since 1994, we have tested serum HCV-IgG antibodies in 783 patients with SS diagnosed according to the 1993 European classification criteria. The immunological profile at diagnosis was compared according to the presence or absence of HCV. RESULTS: Of the 783 patients with SS, 105 (13.4 %) tested positive for HCV-IgG antibodies (88 females, 17 males, mean age at SS diagnosis: 62.9 years). Multivariate analysis showed that patients with SS-HCV had a higher mean age and a higher frequency of low C3/C4 levels, cryoglobulins, and hematological neoplasia compared with patients without HCV. The frequency of anti-La antibodies compared with anti-Ro antibodies was higher in patients with SS-HCV (17 % vs. 15 %) and lower in patients without HCV infection (30 % vs. 43 %). The frequency of concomitant detection of the three main cryoglobulin-related markers (cryoglobulins, rheumatoid factor activity, and C4 consumption) was threefold higher in patients with SS-HCV compared with patients without HCV. SS HCV patients with genotype 1b showed the highest frequencies of immunological abnormalities related to cryoglobulins and the lowest frequencies of anti-Ro/La antibodies. CONCLUSIONS: We found HCV infection in 13 % of a large series of Spanish patients with SS. The HCV-driven autoimmune response was characterized by a lower frequency of anti-Ro/La antibodies, an abnormal predominance of anti-La among anti-Ro antibodies, and a higher frequency of cryoglobulinemic-related immunological markers in comparison with patients without HCV infection. This immunological pattern may contribute to the poor outcomes found in patients with SS-HCV. PMID- 26370715 TI - Characteristics of AA amyloidosis patients in San Francisco. AB - BACKGROUND: AA amyloidosis due to subcutaneous injection of drugs of abuse has been described in the USA, but all the existing literature is from more than 20 years ago. There is more recent literature from Europe. We have observed a high incidence of AA amyloidosis in the county hospital in San Francisco. DESIGN: Here, we describe 24 patients who had kidney biopsy-proven AA amyloidosis from our hospital from 1998 to 2013. All the patients were thought to have AA amyloidosis from skin popping of illicit drugs after having exhausted the intravenous route. These patients with biopsy-proven AA amyloidosis were analysed further. RESULTS: All patients were found to have hepatitis C infection, hypertension was not common, most had advanced kidney failure, and acidosis was common as was tubulointerstitial involvement on the kidney biopsy. Other organ involvement included hepatomegaly and splenomegaly in a number of patients; direct myocardial involvement was not seen, but pulmonary hypertension, history of deep vein thrombosis and pulmonary embolism were common. The prognosis of these patients was poor. The mortality rate approached 50% 1 year after biopsy, and most of the patient needed dialysis shortly after diagnosis. Cessation of drug use seemed beneficial but rarely achievable. CONCLUSION: AA amyloidosis from skin popping is common in San Francisco. Most patients with renal involvement end up on dialysis, and mortality rates are exceedingly high. PMID- 26370713 TI - S100A12 concentrations and myeloperoxidase activity in the intestinal mucosa of healthy dogs. AB - BACKGROUND: Relatively few laboratory markers have been evaluated for the detection or monitoring of intestinal inflammation in canine chronic enteropathies, including inflammatory bowel disease (IBD). Previous research found that the intestinal mucosal levels of S100A12 and myeloperoxidase (MPO), as biomarkers of gut inflammation, were elevated in human patients with IBD. To date, the S100A12 and MPO levels in intestinal mucosal samples from either healthy dogs or from dogs suffering from IBD remain unreported. Therefore, this study aimed to evaluate the mucosal S100A12 and MPO levels in four different parts of the intestine (duodenum, jejunum, ileum and colon) in 12 healthy laboratory Beagle dogs using the ELISA and spectrophotometric methods, respectively. RESULTS: Based on histological examinations, the recorded findings for all the samples were considered normal. The mucosal concentration of S100A12 in the ileum was significantly higher than in all other segments of the intestine (p < 0.05). MPO activity was significantly higher in the ileal, jejunal and duodenal than in colonic mucosal samples (p < 0.05). Moreover, its concentration was higher in the jejunum than in the duodenum. CONCLUSIONS: This study showed that S100A12 and MPO are reliably detectable in canine intestinal mucosa. The assays used appeared to be sufficient to further evaluate the role of S100A12 and MPO in the pathogenesis of canine chronic enteropathies, including IBD. These biomarkers may play a role in the initial detection of gut inflammation suggesting the need for further investigations to confirm IBD or to differentiate between IBD subtypes. Understanding the role of S100A12 and MPO in the pathogenesis of chronic intestinal inflammation in future may result in an improved understanding of canine chronic intestinal inflammation. PMID- 26370716 TI - Radioembolization with (90)Y resin microspheres for intrahepatic cholangiocellular carcinoma: prognostic factors. AB - AIM: To investigate the prognostic factors that predict overall survival after radioembolization in patients with cholangiocellular carcinoma. METHODS: The study comprised 16 patients who received radioembolization with Y(90) resin microspheres for cholangiocarcinoma. The statistical relationships between overall survival after radioembolization and age, number, dimension and fluorodeoxyglucose (FDG) avidity of liver lesions, liver tumor load, presence of extrahepatic metastases, and radiological response were analyzed. RESULTS: Mean 1.7 +/- 0.1 GBq(90)Y microspheres were administered to a total of 16 patients (mean age: 55.37 +/- 17.7; 8 males, 8 females). Mean AST, ALT, and total bilirubin levels were calculated as 35 +/- 15, 40 +/- 37 IU/L, and 0.77 +/- 0.37 mG/dL, respectively. In 6 patients, 1 liver lesion was determined, in 2 patients <= 5, and in 8 patients >5, with dimensions varying between 12 and 120 mm. The liver lesions of 13 patients were FDG avid (mean SUVmax: 7.4 +/- 2.2). Extrahepatic metastases were demonstrated in 5 patients. Tumor load of 4, 8, and 4 patients was calculated as <25, 25-50, and >50%, respectively. Five patients were responsive to treatment. During the follow-up period of 243 (range 98-839) days, 12 patients died. In Cox-regression analysis, FDG avidity (p = 0.02), the dimensions (p = 0.03) of the liver lesion, tumor load (p = 0.02), and radiological response (p = 0.01) were found to be statistically significant parameters predictive of overall survival after radioembolization (p = 0.006). CONCLUSION: FDG avidity and the dimension of the largest liver lesion, tumor load, and radiological response are prognostic factors in patients receiving radioembolization for cholangiocellular carcinoma. Patients with lower tumor load, FDG-negative tumors, and smaller tumors seem to survive longer after radioembolization. PMID- 26370717 TI - (18)F-FDG uptake of the spinal cord was decreased after conventional dose radiotherapy in esophageal cancer patients. AB - OBJECTIVE: We retrospectively investigated changes of (18)F-fluorodeocyglucose ((18)F-FDG) uptake in the spinal cord, inside and outside the radiation fields, in patients with esophageal cancer before and after conventional dose radiotherapy. METHODS: A total of 17 consecutive patients with esophageal cancer (16 males, one female; age 50-83 years, mean 67.0 years), who underwent conventional dose radiotherapy and (18)F-FDG PET/CT before and 5.1 months (range 1.6-8.6 months) after the radiotherapy, were retrospectively evaluated. Sixteen patients had esophageal cancer and one patient had esophageal metastasis from thyroid cancer. Mean standardized uptake values (SUVmean) of the cervical, thoracic (inside and outside the radiation fields) and lumbar spinal cord were measured. RESULTS: SUVmean of the thoracic spinal cord inside the radiation field was decreased significantly after radiotherapy compared to those before radiotherapy (p < 0.001). SUVmean of the cervical spinal cord showed the same trend but it was not statistically significant (p = 0.051). SUVmean of the thoracic spinal cord outside the radiation field and the lumbar spinal cord did not differ significantly before and after the radiotherapy (p = 0.146 and p = 0.701, respectively). CONCLUSIONS: The results suggest that glucose metabolism of the spinal cord is decreased in esophageal cancer patients after conventional dose radiotherapy. PMID- 26370718 TI - In vivo micro-angiography by means of speckle-variance optical coherence tomography (SV-OCT) is able to detect microscopic vascular changes in naevus to melanoma transition. PMID- 26370719 TI - Is the level of institutionalisation found in psychiatric housing services associated with the severity of illness and the functional impairment of the patients? A patient record analysis. AB - BACKGROUND: In this cross-sectional study, we investigated whether clinical, social, financial, and care variables were associated with different accommodation settings for individuals suffering from severe and persistent mental disorders. METHOD: Electronic record data of 250 patients who fulfilled the criteria for persistent and severe mental illness were used. Multiple linear regression models were applied to analyse associations between the types and the costs of housing services and the patients' severity of illness, their functional impairment, and their socio-demographic characteristics. RESULTS: We identified 50 patients living at home without need for additional housing support who were receiving outpatient treatment, 41 patients living in the community with outpatient housing support, 23 patients living with foster families for adults, 45 patients living in group homes with 12-h staff cover, 10 patients living in group homes with 24-h staff, and 81 patients living in psychiatric nursing homes. While this housing differed largely in the level of institutionalisation and also in the costs of accommodation, these differences were not related to a patient's severity of disease or in their functional impairment. In particular, patients living in nursing homes had a slightly higher level of functioning compared to those living in the community without welfare housing services. Only where patients were subject to guardianship was there a significant association with an increased level of institutionalisation. CONCLUSIONS: Our study suggests that the level of institutionalisation and the associated costs of welfare housing services do not accurately reflect the severity of illness or the level of functional impairment of the patients there are designed to support. The limitations of the study design and the data do not allow for conclusions about causal relationships or generalisation of the findings to other regions. Therefore, further prospective studies are needed to assess the adequacy of the setting assignment of patients with persistent severe mental illness into different types of housing settings with appropriate (also welfare) services. PMID- 26370720 TI - Hearing in slow-motion: Humans underestimate the speed of moving sounds. AB - Perception can often be described as a statistically optimal inference process whereby noisy and incomplete sensory evidence is combined with prior knowledge about natural scene statistics. Previous evidence has shown that humans tend to underestimate the speed of unreliable moving visual stimuli. This finding has been interpreted in terms of a Bayesian prior favoring low speed, given that in natural visual scenes objects are mostly stationary or slowly-moving. Here we investigated whether an analogous tendency to underestimate speed also occurs in audition: even if the statistics of the visual environment seem to favor low speed, the statistics of the stimuli reaching the individual senses may differ across modalities, hence potentially leading to different priors. Here we observed a systematic bias for underestimating the speed of unreliable moving sounds. This finding suggests the existence of a slow-motion prior in audition, analogous to the one previously found in vision. The nervous system might encode the overall statistics of the world, rather than the specific properties of the signals reaching the individual senses. PMID- 26370721 TI - Development of a hematogenous implant-related infection in a rat model. AB - BACKGROUND: Implant-related osteomyelitis is a major complication that requires immediate treatment, often involving removal of the implant, prolonging patient recovery and inflating expenses. Current research involving interventions to diminish the prevalence of such measures include investigating prophylactic and therapeutic remedies. A proper and accurate animal model is needed to thoroughly investigate such treatments. The scope of this project was to develop an animal model in which a consistent and measurable infection can be formed on an orthopedic implant when bacteria is introduced via a hematogenous source. METHODS: Titanium Kirschner-wires were implanted into the intramedullary canals of both femurs. Staphylococcus aureus, ranging from10(4) to 10(9) colony forming units, was injected into a tail vessel. After a designated time (3, 7, 14, or 42 days) the femurs were harvested and bacterial numbers determined for both the femur and the implanted K-wire. In addition, histology and micro-computed tomography were used as subjective tools to further characterize the infection. RESULTS: Consistent infection, that is infection of >=75% of the femurs, wasn't achieved until 10(7) CFU S. aureus was injected. At 10(7) CFU, the femurs contained 4.6x10(6) CFU/g bone tissue at day 3 and 4.8*10(8) CFU/g bone tissue by day 14. The wire showed comparable contamination with 4.8*10(4) CFU/mm(2) at day 3 and 3.7*10(5)/mm(2) by day 14. After 42 days, the bacteria number decreased but was still occupying at 1.9*10(5) CFU/g bone tissue. There were morphological changes to the bone as well. At day 42, there were signs of osteonecrosis and active bone formation when compared to control animals that received a K-wire but were inoculated with saline. CONCLUSIONS: A model for hematogenous osteomyelitis, a common complication associated with implants, has been introduced. A reproducible, preclinical model is essential to evaluate future methods used to mitigate blood-borne bacteria hardware and bone infections. PMID- 26370722 TI - A regenerative microchannel device for recording multiple single-unit action potentials in awake, ambulatory animals. AB - Despite significant advances in robotics, commercially advanced prosthetics provide only a small fraction of the functionality of the amputated limb that they are meant to replace. Peripheral nerve interfacing could provide a rich controlling link between the body and these advanced prosthetics in order to increase their overall utility. Here, we report on the development of a fully integrated regenerative microchannel interface with 30 microelectrodes and signal extraction capabilities enabling evaluation in an awake and ambulatory rat animal model. In vitro functional testing validated the capability of the microelectrodes to record neural signals similar in size and nature to those that occur in vivo. In vitro dorsal root ganglia cultures revealed striking cytocompatibility of the microchannel interface. Finally, in vivo, the microchannel interface was successfully used to record a multitude of single-unit action potentials through 63% of the integrated microelectrodes at the early time point of 3 weeks. This marks a significant advance in microchannel interfacing, demonstrating the capability of microchannels to be used for peripheral nerve interfacing. PMID- 26370723 TI - Eligibility criteria in systematic reviews published in prominent medical journals: a methodological review. AB - RATIONALE AND AIM: Clear and logical eligibility criteria are fundamental to the design and conduct of a systematic review. This methodological review examined the quality of reporting and application of eligibility criteria in systematic reviews published in three leading medical journals. METHODS: All systematic reviews in the BMJ, JAMA and The Lancet in the years 2013 and 2014 were extracted. These were assessed using a refined version of a checklist previously designed by the authors. RESULTS: A total of 113 papers were eligible, of which 65 were in BMJ, 17 in The Lancet and 31 in JAMA. Although a generally high level of reporting was found, eligibility criteria were often problematic. In 67% of papers, eligibility was specified after the search sources or terms. Unjustified time restrictions were used in 21% of reviews, and unpublished or unspecified data in 27%. Inconsistency between journals was apparent in the requirements for systematic reviews. CONCLUSIONS: The quality of reviews in these leading medical journals was high; however, there were issues that reduce the clarity and replicability of the review process. As well as providing a useful checklist, this methodological review informs the continued development of standards for systematic reviews. PMID- 26370724 TI - Endoscopic sphenopalatine ganglion blockade efficacy in pain control after endoscopic sinus surgery. AB - BACKGROUND: The objective of this study was to evaluate the efficacy of bilateral endoscopic injection of lidocaine with epinephrine in the sphenopalatine ganglion at the end of endoscopic sinus surgery (ESS) in controlling postoperative pain and rescue analgesic requirements. METHODS: A prospective, double blinded, placebo-controlled clinical trial of 60 patients with chronic rhinosinusitis (CRS) undergoing general anesthesia for ESS was undertaken. Patients were randomized to receive injection of 2 mL of 2% lidocaine with epinephrine or 2 mL saline at the end of surgery. Postoperatively, patients were observed for 24 hours. Pain severity was reported immediately, 6 hours, and 24 hours after surgery using a 10-cm visual analog scale (VAS). The need of rescue analgesia was recorded and compared between the 2 groups. RESULTS: The 2 groups were matched in demographic and intraoperative details. Postoperative pain severity average was 3.4, 3.0, and 1.6 in the saline group compared to 1.6, 1.7, and 1.0 in the lidocaine group. These differences reached statically significant for the first 2 follow-up intervals. Also, there was significant difference in the whole-day postoperative average score between the 2 groups (2.6 vs 1.4). Twelve patients in the saline group required rescue analgesia compared to 5 in the lidocaine group. The average rescue analgesia dose was 27.5 mg of tramadol in the saline group vs 11.6 in the lidocaine group. These differences were statistically significant. No complications were reported in either group. CONCLUSION: Sphenopalatine ganglion injection of lidocaine at the end of surgery is safe, simple, noninvasive, and an effective method of short-term pain control after sinus surgery. PMID- 26370725 TI - Nephrectomy and inferior vena cava thrombectomy for renal cell carcinoma among patients with impaired renal function: defining predictors of outcomes. AB - BACKGROUND: Management of renal cell carcinoma (RCC) with inferior vena cava thrombus (IVCT) is associated with high morbidity. Chronic kidney disease (CKD) is a known risk factor for perioperative complications in many surgical procedures. The objective of this study was to review the association between preoperative CKD (eGFR < 60 mL/min) and post-operative outcomes in patients with RCC and IVCT undergoing radical nephrectomy (RN) and tumour thrombectomy (TT). METHODS: A retrospective review of patients with RCC and IVCT treated with RN and TT was carried out. Complications were recorded according to the Clavien-Dindo classification. Multivariable models were fitted using logistic regression analyses for high-grade complications and salvage therapies and linear-regression for intraoperative blood loss (IBL). RESULTS: One hundred and one patients with RCC and IVCT, treated with RN and TT, were identified. Forty per cent of patients had preoperative CKD. Median IBL was higher in CKD arm (2.5 versus 1.6 L, P = 0.04). In a multivariate linear regression analysis, CKD (beta 1.34, P = 0.01) remained an independent predictor of IBL. High-grade complications were more frequent in the CKD group (34% versus 16%, P = 0.09) and in logistic regression analysis, CKD was an independent predictor of high-grade complications (OR 3.33, 95% CI 1.01-10.9). Furthermore, CKD patients were less likely to be considered for salvage therapies (62% versus 38%, P = 0.02). CONCLUSIONS: In patients treated with RN and TT, CKD is an independent predictor of perioperative morbidity. This clinical variable should be considered when selecting patients and subsequent efforts should be made to optimize other competing risk factors in order to reduce the incidence of perioperative adverse events in this patient population. PMID- 26370727 TI - Targeted therapy: resistance and re-sensitization. AB - The last two decades have witnessed a paradigm shift from cytotoxic drugs to targeted therapy in medical oncology and pharmaceutical innovation. Inspired by breakthroughs in molecular and cellular biology, a number of novel synthesized chemical compounds and recombinant antibodies have been developed to selectively target oncogenic signaling pathways in a broad array of tumor types. Although targeted therapeutic agents show impressive clinical efficacy and minimized adverse effects compared with traditional treatments, the challenging drug resistant issue has also emerged to limit their benefits to cancer patients. In this regard, we aim to improve targeted therapy by presenting a systematic framework regarding the drug resistance mechanisms and alternative approaches to re-sensitize cancer cells/tissues therapeutically. PMID- 26370728 TI - Menstrual blood contains immune cells with inflammatory and anti-inflammatory properties. AB - AIM: Successful pregnancy requires balanced regulation of immune cells at the feto-maternal interface. Systemic monitoring of the immune system cannot precisely outline local immune status in the uterus. In this survey, endometrial immune milieu was investigated using a non-invasive method of analysis of menstrual blood (MB). The results were compared with peripheral blood (PB). METHOD: PB and MB of healthy fertile women (n = 15) were collected simultaneously on the second day of their menstrual cycle. T and natural killer T cell subpopulations were immunophenotyped by flow cytometry. RESULTS: Among examined cell populations, the frequency of CD4 + Foxp3+, CD4 + Foxp3 + CD25-, CD4 + Foxp3 + CD25+ and IL17+ T cells (P = 0.022, 0.028, 0.017 and 0.005, respectively) and TCRalphabeta+, CD45RO+, CD16-, IFNgamma + and IL17+ NKT (CD56 + CD3+) cells (P = 0.010, 0.037, 0.038, 0.015 and 0.021, respectively) were significantly higher in MB compared with PB. Conversely, PB contained a higher percentage of CD16+ T cells (P = 0.025) in comparison with MB. CONCLUSION: MB contains cells of an inflammatory and anti-inflammatory nature, implying the existence of finely tuned cell homeostasis during menstruation. Our results imply that MB could be viewed as an easy-to access specimen for monitoring endometrial immune cells, especially those that have preferential endometrial localization. PMID- 26370730 TI - Adrenal gland: Cancer target of mitotane identified. PMID- 26370726 TI - Diverse regulation of 3' splice site usage. AB - The regulation of splice site (SS) usage is important for alternative pre-mRNA splicing and thus proper expression of protein isoforms in cells; its disruption causes diseases. In recent years, an increasing number of novel regulatory elements have been found within or nearby the 3'SS in mammalian genes. The diverse elements recruit a repertoire of trans-acting factors or form secondary structures to regulate 3'SS usage, mostly at the early steps of spliceosome assembly. Their mechanisms of action mainly include: (1) competition between the factors for RNA elements, (2) steric hindrance between the factors, (3) direct interaction between the factors, (4) competition between two splice sites, or (5) local RNA secondary structures or longer range loops, according to the mode of protein/RNA interactions. Beyond the 3'SS, chromatin remodeling/transcription, posttranslational modifications of trans-acting factors and upstream signaling provide further layers of regulation. Evolutionarily, some of the 3'SS elements seem to have emerged in mammalian ancestors. Moreover, other possibilities of regulation such as that by non-coding RNA remain to be explored. It is thus likely that there are more diverse elements/factors and mechanisms that influence the choice of an intron end. The diverse regulation likely contributes to a more complex but refined transcriptome and proteome in mammals. PMID- 26370729 TI - Self-injurious thoughts and behaviors as risk factors for future suicide ideation, attempts, and death: a meta-analysis of longitudinal studies. AB - BACKGROUND: A history of self-injurious thoughts and behaviors (SITBs) is consistently cited as one of the strongest predictors of future suicidal behavior. However, stark discrepancies in the literature raise questions about the true magnitude of these associations. The objective of this study is to examine the magnitude and clinical utility of the associations between SITBs and subsequent suicide ideation, attempts, and death. METHOD: We searched PubMed, PsycInfo, and Google Scholar for papers published through December 2014. Inclusion required that studies include at least one longitudinal analysis predicting suicide ideation, attempts, or death using any SITB variable. We identified 2179 longitudinal studies; 172 met inclusion criteria. RESULTS: The most common outcome was suicide attempt (47.80%), followed by death (40.50%) and ideation (11.60%). Median follow-up was 52 months (mean = 82.52, s.d. = 102.29). Overall prediction was weak, with weighted mean odds ratios (ORs) of 2.07 [95% confidence interval (CI) 1.76-2.43] for ideation, 2.14 (95% CI 2.00-2.30) for attempts, and 1.54 (95% CI 1.39-1.71) for death. Adjusting for publication bias further reduced estimates. Diagnostic accuracy analyses indicated acceptable specificity (86-87%) and poor sensitivity (10-26%), with areas under the curve marginally above chance (0.60-0.62). Most risk factors generated OR estimates of <2.0 and no risk factor exceeded 4.5. Effects were consistent regardless of sample severity, sample age groups, or follow-up length. CONCLUSIONS: Prior SITBs confer risk for later suicidal thoughts and behaviors. However, they only provide a marginal improvement in diagnostic accuracy above chance. Addressing gaps in study design, assessment, and underlying mechanisms may prove useful in improving prediction and prevention of suicidal thoughts and behaviors. PMID- 26370734 TI - Pfizer loses UK patent for blockbuster pain drug after threats to doctors. PMID- 26370735 TI - Evaluation of the pathogenic potential, antimicrobial susceptibility, and genomic relations of Yersinia enterocolitica strains from food and human origin. AB - Yersinia enterocolitica is a food-borne pathogen that causes gastroenteritis with occasional postinfection sequels. This study was aimed to determinate the pathogenic potential, antimicrobial susceptibility, and genomic relationships of Y. enterocolitica strains of different bioserotypes (B/O) isolated from foods and human samples in San Luis, Argentina. Strains obtained by culture were bioserotyped and characterized by phenotypic and genotypic virulence markers, antimicrobial susceptibility, and pulsed-field gel electrophoresis (PFGE). Yersinia enterocolitica was detected in 9.2% of 380 samples, with a distribution of 10.6% (30/284) for food products and 5.2% (5/96) for human samples. Regarding the pathogenic potential, B1A strains of different serotypes were virF(-) ail(-), of which 72.0% (13/18) were ystB(+) with virulence-related phenotypic characteristics. Among B2/O:9 isolates, 75.0% (9/12) exhibited the genotype virF(+) ail(+) ystB(-) along with phenotypic traits associated with virulence; the same genotype was observed in 80.0% (4/5) of B3/O:3 and B3/O:5 strains. By PFGE, it was possible to separate Y. enterocolitica biotypes into 4 clonal groups (A to D) with 23 genomic types, generating a discriminatory index of 0.96. All isolates were susceptible to antimicrobials used for clinical treatment. This study highlights the presence of pathogenic bioserotypes and the high genomic diversity of the Y. enterocolitica strains isolated in our region. PMID- 26370736 TI - "Giants in a Microcosm": Multinucleated Giant Cells Populating an Invasive Micropapillary Carcinoma of the Breast. PMID- 26370737 TI - Analytical evaluation of nine serological assays for diagnosis of syphilis. AB - BACKGROUND: The diagnosis of syphilis is most frequently dependent on antibody detection with serological assays. Assays for both treponemal and non-treponemal antibodies are needed to provide a sensitive and specific diagnosis. For decades, a first screening has been done with non-treponemal assays, followed by treponemal. However, in recent years, following laboratory automation, the reverse sequence screening algorithms have been developed, using a treponemal assay as the initial screening test. OBJECTIVE: To evaluate serological assays for treponemal and non-treponemal antibodies, to use in reverse algorithm screening of syphilis. MATERIAL AND METHODS: Six treponemal assays (one IgM specific assay), two non-treponemal assays and one novel dual point-of-care (POC) assay for serological diagnosis of syphilis were evaluated. Serum samples from Guinea-Bissau and Sweden were examined, as well as two performance panels and samples from blood donors. Sensitivity and specificity were calculated for each assay, using different assays as gold standard test. RESULTS: The Macro-Vue RPR Card test was the most sensitive non-treponemal test and the TrepSure Anti Treponema EIA Screen and the SeroDia TP-PA were the most sensitive and specific treponemal assays. Among the automated assays, both the Liaison Treponema Screen and Architect Syphilis TP showed high sensitivity, however, the former had clearly higher specificity. CONCLUSIONS: In resourced settings, where the reverse sequence algorithm is preferred for screening, an automated treponemal immunoassay for initial screening subsequently followed by the TrepSure test or TP-PA assay as a second treponemal assay appear highly effective. Finally, a quantitative highly sensitive non-treponemal assay, e.g. the Macro-Vue RPR Card test, could then be used as a supplementary test to evaluate activity of the syphilis infection. PMID- 26370738 TI - Thick methacrylate sections devoid of lost caps simplify stereological quantifications based on the optical fractionator design. AB - In neuroscience, the optical fractionator technique is frequently used for unbiased cell number estimations. Although unbiased in theory, the practical application of the technique is often biased by the necessity of introducing a guard zone at one side of the disector to counter lost caps and/or optical limitations. Restricting the disector within the section thickness potentially introduces bias in two ways. First, the need to measure section thickness in order to obtain the disector height/section thickness fraction is challenging since both microcator measurements, microtome block advance, and measurements on re-embedded sections are potentially biased. Second, disector placement is not uniform random within the section thickness resulting in a bias in most sections with inhomogeneous cell distribution along the z axis. Re-embedded 2 hydroxyethylmethacrylate (hereafter methacrylate) sections were inspected for lost caps to evaluate the possibility of whole section thickness counting with the optical fractionator technique and hippocampal granular cell nucleoli density differences along the z axis were assessed with a z axis analysis. No lost caps were found in the examined re-embedded tissue and an inhomogeneous cell distribution through the section thickness was observed. In thick methacrylate sections devoid of lost caps sampling through the entire section thickness could be an acceptable alternative to the use of guard zones and the consequent biases associated with section thickness measurement and non-random placement of disectors. PMID- 26370739 TI - Pulmonary endarterectomy as treatment for chronic thromboembolic pulmonary hypertension in sickle cell disease. PMID- 26370740 TI - The b(c) allele of TYRP1 is causative for the recessive brown (liver) colour in German Shepherd dogs. PMID- 26370743 TI - Photo- and thermochromic and adsorption properties of porous coordination polymers based on bipyridinium carboxylate ligands. AB - The zwitterionic bipyridinium carboxylate ligand 1-(4-carboxyphenyl)-4,4' bipyridinium (hpc1) in the presence of 1,4-benzenedicarboxylate anions (BDC(2-)) and Zn(2+) ions affords three porous coordination polymers (PCPs): [Zn5(hpc1)2(BDC)4(HCO2)2].2DMF.EtOH.H2O (1), [Zn3(hpc1)(BDC)2(HCO2)(OH)(H2O)].DMF.EtOH.H2O (2), and [Zn10(hpc1)4(BDC)7(HCO2)2(OH)4(EtOH)2].3DMF.3H2O (3), with the formate anions resulting from the in situ decomposition of dimethylformamide (DMF) solvent molecules. 1 and 3 are photo- and thermochromic, turning dark green as a result of the formation of bipyridinium radicals, as shown by electron paramagnetic resonance measurements. Particularly, crystals of 3 are very photosensitive, giving an eye-detectable color change upon exposure to the light of the microscope in air within 1-2 min. A very nice and interesting feature is the regular discoloration of crystals from the "edge" to the "core" upon exposition to O2 (reoxidation of organic radicals) due to the diffusion of O2 inside the pores, with this discoloration being slower in an oxygen-poor atmosphere. The formation of organic radicals is explained by an electron transfer from the oxygen atoms of the carboxylate groups to pyridinium cycles. In the structure of 3', [Zn10(hpc1)4(BDC)7(OH)6(H2O)2], resulting from the heating of sample 3 (desolvation and loss of CO molecules due to the decomposition of formate anions), no suitable donor-acceptor interaction is present, and as a consequence, this compound does not exhibit any chromic properties. The presence of permanent porosity in desolvated 1, 2, and 3' is confirmed by methanol adsorption at 25 degrees C with the adsorbed amount reaching 5 wt % for 1, 10 wt % for 3', and 13 wt % for 2. The incomplete desorption of methanol at 25 degrees C under vacuum points to strong host-guest interactions. PMID- 26370742 TI - Raising the Bar in Renal Sympathetic Denervation Research and Reporting. PMID- 26370741 TI - MicroRNA125b-mediated Hedgehog signaling influences liver regeneration by chorionic plate-derived mesenchymal stem cells. AB - Although chorionic plate-derived mesenchymal stem cells (CP-MSCs) were shown to promote liver regeneration, the mechanisms underlying the effect remain unclear. Hedgehog (Hh) signaling orchestrates tissue reconstruction in damaged liver. MSCs release microRNAs mediating various cellular responses. Hence, we hypothesized that microRNAs from CP-MSCs regulated Hh signaling, which influenced liver regeneration. Livers were obtained from carbon tetrachloride (CCl4)-treated rats transplanted with human CP-MSCs (Tx) or saline (non-Tx). Sonic Hh, one of Hh ligands, increased in CCl4-treated liver, whereas it decreased in CP-MSC-treated liver with CCl4. The expression of Hh-target genes was significantly downregulated in the Tx. Reduced expansion of progenitors and regressed fibrosis were observed in the liver of the Tx rats. CP-MSCs suppressed the expression of Hh and profibrotic genes in co-cultured LX2 (human hepatic stellate cell) with CP MSCs. MicroRNA-125b targeting smo was retained in exosomes of CP-MSCs. CP-MSCs with microRNA-125b inhibitor failed to attenuate the expression of Hh signaling and profibrotic genes in the activated HSCs. Therefore, these results demonstrated that microRNA-125b from CP-MSCs suppressed the activation of Hh signaling, which promoted the reduced fibrosis, suggesting that microRNA-mediated regulation of Hh signaling contributed to liver regeneration by CP-MSCs. PMID- 26370744 TI - The Epidemiologic and Clinical Findings of Patients with Buerger Disease. AB - BACKGROUND: Buerger disease is a nonatherosclerotic peripheral arterial disease, which is mostly observed in young male smokers. Buerger disease is characterized by the observation of peripheral arterial occlusion by angiography. The condition may be caused by microembolization in the small-sized arteries of the distal extremities. Buerger disease is diagnosed based on the Shionoya's clinical diagnostic criteria, which include: (1) a history of smoking, (2) onset before the age of 50 years, (3) the presence of infrapopliteal arterial occlusions, (4) either upper limb involvement or phlebitis migrans, and (5) the absence of atherosclerotic risk factors other than smoking. Several studies have reported that oral bacterial infections (periodontitis) could activate the onset of Buerger disease. In this study, we report the epidemiologic and clinical manifestations of patients with Buerger disease. METHODS: Fifty-eight patients who were surgically treated between July 1989 and June 2014 at Tokyo Medical and Dental University Hospital were enrolled in this study. All of the patients clinically diagnosed with Buerger disease based on Shionoya's clinical diagnostic criteria. Fifty-five male and 3 female patients were treated. The mean age of the patients was 48 years (range, 21-73 years). RESULTS: All of the patients were either smokers or had a history of smoking. The mean Brinkman index score was 780 (range, 150-1,640). Their mean age at the onset of Buerger disease was 38 years (range, 21-50). The arterial lesions extended to the femoral arteries in 25% of cases, to the iliac arteries in 8% and to the abdominal aorta and/or visceral arteries in 6% of cases. Upper limb involvement, including cyanosis, paleness, and gangrene, was obvious in 84% of patients, and phlebitis migrans was recognized in 34%. The lower extremities symptoms involved intermittent claudication in 23% of the patients, rest pain in 13% of the patients, and ulceration or gangrene in 64% of the patients. Fifteen patients had undergone surgical arterial reconstruction, 4 patients had received endovascular therapy, 33 patients had undergone lumbar sympathectomy and 8 patients had undergone thoracic sympathectomy. Twenty percent of the patients needed minor limb amputations, and 4% required major limb amputations. In the patients who were examined for their oral conditions, periodontitis corresponding to grades B (moderate periodontitis), C (severe periodontitis), and D (edentulous patients) was revealed in 31%, 56%, and 13% of the patients, respectively. CONCLUSIONS: More than half of the Buerger disease patients in this study were suffering from severe periodontitis. It is possible that not only the cessation of smoking, but also the improvement of periodontal care could improve the clinical symptoms related to Buerger disease. PMID- 26370745 TI - Diabetic Foot Infection: Preliminary Results of a Fast-Track Program with Early Endovascular Revascularization and Local Surgical Treatment. AB - BACKGROUND: To demonstrate that a fast-track program consisting in early endovascular revascularization and local surgical treatment saves tissue in patients with diabetic foot infection (DFI). METHODS: Between January and December 2014, 48 patients with DFI underwent early endovascular revascularization and local surgical treatment at our Diabetic Foot Center. In all cases, endovascular revascularization and local surgical treatment were performed within 1 week from the diagnosis of infection and during the same hospital stay. One-year outcomes were evaluated in terms of survival, primary patency, primary-assisted patency, secondary patency, absence of target lesion restenosis (TLR), and limb salvage. RESULTS: The patients were predominantly males (34 of 48, 70.8%) with a mean age of 72.4 years (range, 51-91). The target vessel was a tibial artery in 34 cases (70.8%). Surgical treatment consisted of debridement without bone resection in 27 cases (56.2%), toe and/or ray amputation in 15 cases (31.2%), Lisfranc amputation in 2 cases (4.2%), transmetatarsal amputation in 2 cases (4.2%). In the remaining 2 cases, a leg amputation was necessary with an overall 30-day major amputation rate of 4.2%. During the follow up (mean duration 6.9 months, range 1-12) healing of the lesions was obtained in 30 cases (62.5%). Estimated 12-month survival, primary patency, primary-assisted patency, secondary patency, absence of TLR, and limb salvage rates were 83.5%, 53.4%, 65%, 65%, 60.7%, and 86.6%, respectively. CONCLUSIONS: A fast-track program consisting in early endovascular revascularization and local surgical treatment contributes to our experience in limiting amputation levels in patients with DFI. A multidisciplinary approach and adoption of diabetic foot triage are essential to achieve these outcomes. PMID- 26370746 TI - Aortic Arch Mapping by Computed Tomography for Actual Anatomic Studies in Times of Emerging Endovascular Therapies. AB - BACKGROUND: The latest advances in treatment of aortic arch pathologies increasingly included endovascular technologies. For those purposes, more detailed knowledge about the specific anatomic features are of particular interest, especially with regard on the need for better suitable stent grafts or even development of "off-the-shelf" stents. METHODS: The study enrolled patients undergoing computed tomography of the chest for other reasons than screening for aortic disease. Patients with aortic pathologies were excluded. Finally, 118 patients were included. Anatomic features of the aortic arch, the supra-aortic branches, distances and takeoff angles as well as specific diameters were assessed and analyzed with respect to the patients height, weight, age, and sex. RESULTS: A significant variability of all measurements was observed. Nonetheless, 4 recurrent types of aortic arch geometry were identified: (1) Classic arch (39%), (2) Gothic arch (39%), (3) Rectangle arch (11.9%), and (4) Plain arch (8.5%). Furthermore, the aortic diameter continuously decreased from the beginning of the ascending aorta during the after 200 mm by 24.8% (31.8 +/- 3.6 mm to 23.9 +/- 3.1 mm in mean). Distances from the aortic annulus to the supra aortic branches takeoff points showed significant gender- and age-related differences with larger distances in the older and male (P < 0.001). Observed takeoff angles were 44.9 +/- 15.9 degrees for the brachiocephalic trunk, 25.7 +/ 15.5 degrees for the left common carotid artery, and 28.8 +/- 14.5 degrees for the left subclavian artery. CONCLUSIONS: Observed anatomic features were highly variable. It seemed that a "standard aortic arch" does not exist. Until today, the aortic arch as a dynamic and 3-dimensional entity is not fully understood. The development of "off-the-shelf" stents in the near future will be limited by this complexity and variability. PMID- 26370747 TI - Predictors of Discharge Home after Blunt Traumatic Thoracic Aortic Injury. AB - BACKGROUND: Blunt traumatic thoracic aortic injury (BTAI) can be a highly lethal injury but in the last decade major advances have been made in diagnostic accuracy, injury grading, and therapy. Traditionally, emphasis has been on studying survival postinjury with a paucity of studies examining the discharge characteristics of patients that survive a BTAI. The purpose of this study is to define the epidemiology and predictors of disposition in patients with BTAI in a provincial database. METHODS: Using the Ontario Trauma Registry, all patients were identified who were hospitalized with a BTAI between 1999 and 2009. Trends in therapy and discharge disposition were determined. RESULTS: We identified 264 cases of BTAI. Of these, 157 were discharged from hospital with 36% (n = 56) going directly home and 64% (n = 101) going to continuing care facilities. There was no difference in disposition in those with BTAI treated operatively or nonoperatively (P = 0.48). In those that had repair of BTAI, there was no difference in discharge home between open and endovascular repair (P = 1.00). Univariate analyses identified younger age, male sex, lower injury severity score (ISS), and lower Charlson comorbidity indices as being predictors of discharge home. On adjusted multivariate regression analysis, lower ISS (odds ratio, 0.91; 95% confidence interval, 0.87-0.95; P < 0.001) was the only independent predictors of discharge home. CONCLUSIONS: Our findings suggest that the only independent predictor for discharge home for patients who survive is the overall severity of all their injuries irrespective of their condition on admission or management of their BTAI. PMID- 26370748 TI - Seven-Year Approach Evolution of the Aortoiliac Occlusive Disease Endovascular Treatment. AB - BACKGROUND: Endovascular treatment is now considered the first-line therapy for the aortoiliac occlusive disease (AIOD). We report our experience with the total endovascular treatment of infrarenal and pararenal aortoiliac occlusions and the 7-year approach evolution. METHODS: A total of 22 patients underwent total endovascular treatment of AIOD from January 2008 to September 2014. Bare metal stents in kissing configuration were deployed in 9 cases, covered stents in kissing configuration in 9 patients and the aortic bifurcation reconstruction with the Y-guidewire configuration technique was performed in the last 4 patients. RESULTS: Technical success was 100%. Perioperative mortality rate was 4.5%. ankle-brachial index improved from 0.49 +/- 0.19 to 0.96 +/- 0.05 at the right side and from 0.53 +/- 0.17 0.98 +/- 0.04 at the left side (P < 0.01). Mean follow-up was 39.5 months (range, 5-80 months). The primary patency rate was 95.2% at 1 year and 90.5% at 3 years, and the secondary patency rate was 95.2% at 1 year and 100% at 3 years. CONCLUSIONS: Different stent types and configurations used for the aortoiliac endovascular treatment offer all the benefits of these materials for treatment on a case-by-case basis. The Y-guidewire configuration technique for the aortic bifurcation reconstruction may render the procedure more feasible. More cases and longer follow-up are necessary before the widespread use of this technique. PMID- 26370749 TI - Partnership and rigor in improving patient care. PMID- 26370750 TI - The art and science of marketing medications. PMID- 26370751 TI - Target CLAB Zero: A national improvement collaborative to reduce central line associated bacteraemia in New Zealand intensive care units. AB - AIM: Central line-associated bacteraemia (CLAB) is a preventable cause of patient morbidity and mortality in intensive care units. Target CLAB Zero was a national campaign that ran from October 2011 to March 2013 across all New Zealand ICUs (intensive care units). The campaign aimed to reduce the national CLAB rate to less than one incident per 1,000 line days and to establish a national measurement system for CLAB. METHOD: We used Institute for Healthcare Improvement (IHI) Breakthrough Series methodology to structure the campaign. IHI bundles of care for catheter insertion and maintenance were implemented across 25 New Zealand ICUs. We collected monthly data on line days, CLAB infections and compliance with the bundles. Data were analysed using run charts. RESULTS: The rate of CLAB per 1,000 line days fell from 3.32 at baseline to an average of 0.28 between April 2012 and March 2013. In the final 3-month period, January to March 2013, average insertion bundle compliance was 80% and average maintenance bundle compliance was 75%. All ICUs participated in the collaborative. Over 90% of those invited attended all three national learning sessions and bi-monthly regional learning sessions. CONCLUSION: National collaboratives can effect improvement and shared learning in New Zealand. International evidence combined with New Zealand experience, a supportive methodology, partnership, clinical respect and an effective communication plan were keys to successful engagement. PMID- 26370752 TI - Randomised controlled trials cited in pharmaceutical advertisements targeting New Zealand health professionals: do they support the advertising claims and what is the risk of bias? AB - AIMS: To determine whether pharmaceutical advertisement claims targeting health professionals were supported by the randomised controlled trials (RCTs) cited in the advertisements, and to assess the risk of bias in those trials. METHODS: Pharmaceutical advertisements were obtained from New Zealand Doctor and Pharmacy Today for the period July 2013 to June 2014. All claims made regarding efficacy, safety, and indications were identified and RCTs cited to substantiate these claims were examined. A claim was defined as supported by an RCT if the conclusions drawn in the paper were consistent with the claim. The quality of the RCT was assessed separately, using the Cochrane Risk of Bias Assessment Tool. RESULTS: In 25 (19%) of the 133 instances in which an RCT was cited, the published paper did not support the promotional claim. Moreover, there were only 10 (8%) instances in which the claim was supported by an RCT with a low risk of bias. Of the 78 cited RCTs, only 14% had a low risk of bias, while 49% had an unclear risk and 37% had a high risk. CONCLUSIONS: A high proportion of advertisements failed to meet New Zealand regulatory requirements that claims "are valid and have been substantiated". PMID- 26370753 TI - Hospital admissions for non-cystic fibrosis bronchiectasis in New Zealand. AB - AIM: To investigate hospital admissions for non-cystic fibrosis bronchiectasis during July 1, 2008 to June 30, 2013; and to describe their distribution and annual cost in New Zealand. METHODS: Admissions with a principal diagnosis of bronchiectasis (ICD10 J47), excluding cystic fibrosis, and length of stay <90 days were analysed by age, sex, ethnicity, socioeconomic deprivation, DHB, re admissions and seasonality. RESULTS: There were 5,494 admissions with a mean annual rate of 25.7 (age adjusted rate 20.4) per 100,000. Admission rates peaked in childhood and in the elderly, and increased steeply with socioeconomic deprivation. Age-adjusted rates were 38% higher for women, 4.9-fold higher for Maori and 9.1-fold higher for Pacific peoples. Counties Manukau had the highest unadjusted rate for any DHB (49.4 per 100,000). The overall 30 day readmission rate was 12.4%. Admissions peaked in winter and spring. The estimated cost in financial year 2012/13 was NZD 5.34M. CONCLUSION: Hospital admissions for bronchiectasis are concentrated in socioeconomically disadvantaged young and elderly Maori and Pacific peoples; are more common in winter and spring, and incur a high annual cost. Evidence-based interventions to reduce the disproportionate burden of bronchiectasis in Maori and Pacific children and the elderly is a public health priority. PMID- 26370754 TI - Understanding administrative coding of emergency department visits for unspecified acute allergic reactions. AB - AIM: Emergency department (ED) visits for food-related acute allergic reactions enable estimation of temporal trends in food allergy prevalence. To use this approach in New Zealand requires an understanding of the proportion of ED visits coded as 'anaphylaxis, unspecified' or 'allergy, unspecified' that are food related allergic reactions. METHOD: We reviewed all ED presentations of children, coded as 'anaphylaxis, unspecified' or 'allergy, unspecified', from 1988-2011 to the Auckland City Hospital ED. Charts were reviewed independently by two investigators to determine agreement on categorisation of presentations as being food-related acute allergic reactions. We compared ED presentation rates in different time intervals using rate ratios (RR) and 95% confidence intervals (CI). RESULTS: Sixty-five (29%) of the 221 ED presentations given a discharge code of 'anaphylaxis, unspecified' or 'allergy, unspecified', were a food-related allergic reaction. Inter-observer agreement was very good (kappa >0.80). The ED presentation rate with food-related allergic reactions in 2004-2011 was 98% higher than in 1988-1995 (RR=1.98, 95%CI 1.10-3.72). By contrast, ED presentation rates for non-food-related allergic reactions did not change over these years. CONCLUSION: ED presentations for food-related allergic reactions are identifiable from within ED presentations coded as 'anaphylaxis, unspecified' or 'allergy, unspecified'. ED presentations for food-related allergic reactions have increased over time in Auckland. PMID- 26370755 TI - What have five years of the shorter stays in the emergency department health target done to us? AB - This paper reviews the first five years of the shorter stays in the emergency department national health target--its genesis, implementation and impact. Five years of the target have seen a maturing 'whole-of-system' collaboration leading to better patient care. However, there is still much to do and demand continues to increase. Assisted by the Quality framework and suite of quality measures for the Emergency Department phase of acute patient care in New Zealand, a good structure and methodology driving improvement, and a patient centred focus, this work must continue. PMID- 26370756 TI - Regulating our emergency care paramedics. AB - Ambulance paramedics administering emergency care to patients are delivering a health service as defined in the Health Practitioners Competence Assurance Act, 2003. Paramedics practice a wide range of skills without direct supervision and these can potentially put the public at risk if the paramedic is not competent. Paramedic practice is also rapidly expanding beyond the traditional ambulance role. However, this emerging profession falls outside the Act and paramedics remain unregistered. In this paper we state the case for extending regulation to these frontline healthcare professionals. PMID- 26370757 TI - Post lumbar puncture leg weakness mimicking cauda equina syndrome. PMID- 26370758 TI - Heerfordt's syndrome. PMID- 26370759 TI - Susceptibility to e-cigarette use among never-users: findings from a survey of New Zealand adult smokers and ex-smokers. PMID- 26370760 TI - Did we have the wrong debate about ElixinolTM and medicinal cannabis? PMID- 26370761 TI - A response to 'Childhood obesity in New Zealand' by Steven Kelly, Boyd Swinburn. PMID- 26370762 TI - Smartphone apps for weight loss and smoking cessation: Quality ranking of 120 apps. PMID- 26370763 TI - Paediatric empyema in New Zealand. PMID- 26370764 TI - Response to Briggs, et al. PMID- 26370765 TI - Chewing the saturated fat: how many more negative studies do we need? PMID- 26370766 TI - A snapshot of antimicrobial use in New Zealand hospitals--a comparison to Australian and English data. PMID- 26370767 TI - 3D programme, Sunday August 2, on screening mammography. PMID- 26370768 TI - Zebrafish jam-b2 Gal4-enhancer trap line recapitulates endogenous jam-b2 expression in extraocular muscles. AB - BACKGROUND: Members of the junctional adhesion molecule (JAM) family function as cell adhesion molecules and cell surface receptors. The zebrafish genome contains six different jam genes, and jam-b and jam-c were shown to be essential for myoblast fusion during skeletal muscle development. However, little is known about jam-b2 expression and function. RESULTS: We isolated the cDNA of zebrafish jam-b2. jam-b2 is expressed specifically in extraocular muscles (EOMs), jaw muscles, and pectoral fins in zebrafish larvae, but not in trunk muscles. The identified jam-b2 expression pattern is supported by the analysis of a zebrafish Gal4-enhancer trap line, in which the coding sequence of the transcriptional activator KalTA4 together with a Gal4-dependent UAS-mCherry expression cassette was inserted into the jam-b2 locus. Intercrosses with an UAS:EGFP strain proves the possibility for targeting transgene expression to EOMs, jaw muscles and fins. Finally, we characterized the concerted contraction pattern of EOMs in larvae performing an optokinetic response. CONCLUSIONS: The expression pattern of jam-b2 suggests that it may contribute different properties to EOMs, jaw muscles, and pectoral fins. The jam-b2:KalTA4-UAS-mCherry transgenic strain serves a dual role as both a reporter for these muscles and as a valuable genetic tool for targeting transgene expression to EOMs. PMID- 26370769 TI - Changes in the oral health-related quality of life in children following comprehensive oral rehabilitation under general anaesthesia. AB - OBJECTIVES: To assess changes in the oral health-related quality of life (OHRQoL), after comprehensive oral rehabilitation under general anaesthesia (CORGA), among children (i) <6 years using the Early Childhood Oral Health Impact Scale (ECOHIS) and (ii) aged 6-14 years using the child oral health-related quality of life (COHRQoL) instrument. METHODS: A total of 136 healthy children who had CORGA were recruited over a period of 12 months. The parent or caregiver of the study participants completed the age-appropriate questionnaire prior to the dental treatment and at the subsequent follow-up appointments (2 weeks and 3 months). Data were analysed using repeated-measures anova and Bonferroni tests. RESULTS: The overall ECOHIS scores decreased significantly (P < 0.001) demonstrating large effect sizes. The greatest decreases were for the domains of child oral symptoms (57.5%) and psychology (38.7%) in the child impact section (CIS) and for the domain of parental distress (38.9%) and family function (40%) in the family impact section (FIS). For COHRQoL, the overall P-CPQ and FIS scores decreased significantly for all items (P < 0.001), demonstrating large effect sizes. The greatest decreases were for the domains of oral symptoms (77.7%), functional limitations (74.3%), and the FIS (80.1%). CONCLUSIONS: The OHRQoL of children in both age groups (<6 and 6-14 years) was significantly improved after CORGA. PMID- 26370770 TI - The origins of the universe: why is there something rather than nothing? AB - Perhaps the greatest mystery is why the universe exists in the first place. How is it possible for something to emerge from nothing, or has a universe in some form always existed? This question of origins-both of the universe as a whole and of the fundamental laws of physics-raises profound scientific, philosophical, and religious questions, culminating in the most basic existential question of all: Why are we here? Discussion of this and related questions is presented in this paper. PMID- 26370771 TI - Stacked bilayer phosphorene: strain-induced quantum spin Hall state and optical measurement. AB - Bilayer phosphorene attracted considerable interest, giving a potential application in nanoelectronics owing to its natural bandgap and high carrier mobility. However, very little is known regarding the possible usefulness in spintronics as a quantum spin Hall (QSH) state of material characterized by a bulk energy gap and gapless spin-filtered edge states. Here, we report a strain induced topological phase transition from normal to QSH state in bilayer phosphorene, accompanied by band-inversion that changes number from 0 to 1, which is highly dependent on interlayer stacking. When the bottom layer is shifted by 1/2 unit-cell along zigzag/armchair direction with respect to the top layer, the maximum topological bandgap 92.5 meV is sufficiently large to realize QSH effect even at room-temperature. An optical measurement of QSH effect is therefore suggested in view of the wide optical absorption spectrum extending to far infra red, making bilayer phosphorene a promising candidate for opto-spintronic devices. PMID- 26370772 TI - Glutathione-S-transferases M1/T1 gene polymorphisms and endometriosis: a meta analysis in Chinese populations. AB - In view of the controversies surrounding the glutathione-S-transferases (GST) M1/T1-endometriosis association, a meta-analysis of the GSTM1/GSTT1 genetic association studies of endometriosis was performed in Chinese populations. PubMed, Springer Link, OvidSP, and Chinese databases were searched for related studies. A total of nine studies on GSTM1-endometriosis involved 874 cases and 997 controls, and five studies on GSTT1 involved 404 cases and 513 controls were included in this meta-analysis. Overall, the null genotype of GSTM1/GSTT1 was significantly related to endometriosis risk in Chinese populations (GSTM1, OR = 2.21, 95% CI: 1.22-4.01; GSTT1, OR = 2.31, 95% CI: 1.34-3.99). In subgroup analyses stratified by ethnicity and source of controls, the same results were observed in Chinese Han and population-based studies. The sensitivity analysis confirmed the reliability and stability of the meta-analysis. No publication bias was found among studies by Egger's test. In conclusion, our meta-analysis supports that the GSTM1/GSTT1 null genotype might contribute to individual susceptibility to endometriosis in Chinese populations, especially in Chinese Han. PMID- 26370773 TI - Comparative genome-based identification of a cell wall-anchored protein from Lactobacillus plantarum increases adhesion of Lactococcus lactis to human epithelial cells. AB - Adhesion to host cells is considered important for Lactobacillus plantarum as well as other lactic acid bacteria (LAB) to persist in human gut and thus exert probiotic effects. Here, we sequenced the genome of Lt. plantarum strain NL42 originating from a traditional Chinese dairy product, performed comparative genomic analysis and characterized a novel adhesion factor. The genome of NL42 was highly divergent from its closest neighbors, especially in six large genomic regions. NL42 harbors a total of 42 genes encoding adhesion-associated proteins; among them, cwaA encodes a protein containing multiple domains, including five cell wall surface anchor repeat domains and an LPxTG-like cell wall anchor motif. Expression of cwaA in Lactococcus lactis significantly increased its autoaggregation and hydrophobicity, and conferred the new ability to adhere to human colonic epithelial HT-29 cells by targeting cellular surface proteins, and not carbohydrate moieties, for CwaA adhesion. In addition, the recombinant Lc. lactis inhibited adhesion of Staphylococcus aureus and Escherichia coli to HT-29 cells, mainly by exclusion. We conclude that CwaA is a novel adhesion factor in Lt. plantarum and a potential candidate for improving the adhesion ability of probiotics or other bacteria of interest. PMID- 26370775 TI - The complete plastome sequence of Gnetum ula (Gnetales: Gnetaceae). AB - This study reports the complete plastome sequence of Gnetum ula, a gymnosperm species of Gnetaceae (Gnetophyta). The plastome is 113 249 bp long. It has a quadripartite structure containing a pair of large inverted repeat regions of 19 772 bp each, a large single-copy region of 64 914 bp, and a small single-copy region of 8791 bp. One hundred sixteen genes were predicted in the plastome, including 68 protein-coding genes, eight ribosomal RNA genes, and 40 transfer RNA genes. The gene density is 1.024 (genes/kb). Similar to other known Gnetum plastomes, the G.ula plastome has lost 20 protein-coding genes commonly present in other seed plant plastomes. Our phylogenetic analyses indicate that the four sampled Gnetum species are monophyletic and that G. ula is close to the two other lianas rather than the only small tree species, G. gnemon. Our phylogenetic trees also indicate that gnetophytes have the fastest evolutionary rates among gymnosperms. PMID- 26370776 TI - Independent Composition and Size Control for Highly Luminescent Indium-Rich Silver Indium Selenide Nanocrystals. AB - Ternary I-III-VI nanocrystals, such as silver indium selenide (AISe), are candidates to replace cadmium- and lead-based chalcogenide nanocrystals as efficient emitters in the visible and near IR, but, due to challenges in controlling the reactivities of the group I and III cations during synthesis, full compositional and size-dependent behavior of I-III-VI nanocrystals is not yet explored. We report an amide-promoted synthesis of AISe nanocrystals that enables independent control over nanocrystal size and composition. By systematically varying reaction time, amide concentration, and Ag- and In precursor concentrations, we develop a predictive model for the synthesis and show that AISe sizes can be tuned from 2.4 to 6.8 nm across a broad range of indium-rich compositions from AgIn11Se17 to AgInSe2. We perform structural and optical characterization for representative AISe compositions (Ag0.85In1.05Se2, Ag3In5Se9, AgIn3Se5, and AgIn11Se17) and relate the peaks in quantum yield to stoichiometries exhibiting defect ordering in the bulk. We optimize luminescence properties to achieve a record quantum yield of 73%. Finally, time-resolved photoluminescence measurements enable us to better understand the physics of donor-acceptor emission and the role of structure and composition in luminescence. PMID- 26370774 TI - Investigating determinants of catastrophic health spending among poorly insured elderly households in urban Nigeria. AB - BACKGROUND: In the absence of functional social security mechanisms for elderly people in Nigeria, elderly households are solely responsible for geriatric healthcare costs, which can lead to catastrophic health expenditures (CHE) - particularly among the poor. This study investigates the key determinants of CHE among poorly insured elderly households in Nigeria. We also offer some policy options for reducing the risk of CHE. METHODS: Data on out-of pocket payments and self-reported health status were sourced from the Nigerian General Household Panel Survey (NGHPS) in Nigeria, conducted by the National Bureau of Statistics in 2010, with technical support from the World Bank. CHE was defined at the 10% of total consumption expenditure threshold. The determinants of CHE and their marginal effects were investigated using probit regressions. An elderly household is defined as a household with at least one elderly member >= 50 years old. RESULTS: The proportion of elderly households with CHE is 9.6%. Poorer and smaller elderly households were most at risk of CHE. Female-headed households were less likely to incur CHE compared to male-headed households (p < 0.01). Conversely, households with informal health financing arrangements were less likely to incur CHE (p < 0.001). Education and utilising a health promoting tool, such as treated bednets increased the probability of incurring CHE in Urban Nigeria. CONCLUSION: Findings from this paper should prompt policy action to financially support poor elderly households at risk of CHE in Urban Nigeria. The Nigerian government should enhance the national health insurance scheme to provide better coverage for elderly people, thereby protecting elderly households from incurring CHE. PMID- 26370777 TI - Ventricular dysfunction and aortic dilation in patients with recessive dystrophic epidermolysis bullosa. PMID- 26370779 TI - [Maxillary sinus infection by Bacillus licheniformis: a case report from Djibouti]. AB - Aerobic, spore-forming gram-positive Bacillus spp infections are rare and reported mainly in immunocompromised hosts. We report a case of acute unilateral maxillary sinusitis, caused by Bacillus licheniformis, in a 35-year-old French soldier stationed in Djibouti. It was easily identifiable due to its typical culture and resistance profile. This case is interesting for two reasons: first, it is, to our knowledge, the first case of sinusitis attributed to this microbe, and second, it has rarely been described in immunocompetent patients without altered skin or mucous membranes. PMID- 26370778 TI - Differential Mitochondrial Function in Remodeled Right and Nonremodeled Left Ventricles in Pulmonary Hypertension. AB - OBJECTIVES: Right ventricular failure is the primary reason for mortality in pulmonary hypertension (PH), but little is understood about the energetics of the failing right myocardium. Our aim was to examine mitochondrial function and proteomic signatures in paired remodeled right (RM-RV) and non-remodeled left (NRM-LV) ventricular tissue samples procured during heart-lung transplantation. METHODS AND RESULTS: Contractile dysfunction in RM-RV and preserved contractile function in NRM-LV were determined clinically and by echocardiography. Mitochondria were isolated from fresh paired RV and LV wall specimens of explanted hearts. Respiratory states in response to 4 substrates and an uncoupler were analyzed. Proteomic analysis on the mitochondrial isolates was performed with the use of liquid chromatography-mass spectrometry. The RM-RV mitochondria exhibited higher succinate state 4 levels with lower respiratory control ratio (RCR) compared with state 4 levels for pyruvate-malate (PM) and glutamate-malate (GM). RM-RV mitochondria also exhibited lower state 3 for palmitoyl-carnitine (PC) and state 4 for all complex I substrates compared with NRM-LV. The mean RCR were greater in RM-RVs than in NRM-LVs for PM and GM, which is consistent with tight coupling (low state 4 rates, higher RCRs); however, low RM-RV state 3 rates suggest concurrent substrate-dependent impairment in respiratory capacity. Mitochondrial proteomics revealed greater levels of mitochondrial ADP-ATP translocase and proteins of ATP synthesis, mitochondrial pyruvate and short branched chain acyl-CoA metabolism in RM-RV. CONCLUSIONS: The mitochondrial respiration and proteomics in RM-RV are different from NRM-LV. These results have important implications in expanding our understanding of RV metabolism and future management of RV failure. PMID- 26370780 TI - Long-term stormwater quantity and quality analysis using continuous measurements in a French urban catchment. AB - The assessment of urban stormwater quantity and quality is important for evaluating and controlling the impact of the stormwater to natural water and environment. This study mainly addresses long-term evolution of stormwater quantity and quality in a French urban catchment using continuous measured data from 2004 to 2011. Storm event-based data series are obtained (716 rainfall events and 521 runoff events are available) from measured continuous time series. The Mann-Kendall test is applied to these event-based data series for trend detection. A lack of trend is found in rainfall and an increasing trend in runoff is detected. As a result, an increasing trend is present in the runoff coefficient, likely due to growing imperviousness of the catchment caused by urbanization. The event mean concentration of the total suspended solid (TSS) in stormwater does not present a trend, whereas the event load of TSS has an increasing tendency, which is attributed to the increasing event runoff volume. Uncertainty analysis suggests that the major uncertainty in trend detection results lies in uncertainty due to available data. A lack of events due to missing data leads to dramatically increased uncertainty in trend detection results. In contrast, measurement uncertainty in time series data plays a trivial role. The intra-event distribution of TSS is studied based on both M(V) curves and pollutant concentrations of absolute runoff volumes. The trend detection test reveals no significant change in intra-event distributions of TSS in the studied catchment. PMID- 26370781 TI - Lipid suppression via double inversion recovery with symmetric frequency sweep for robust 2D-GRAPPA-accelerated MRSI of the brain at 7 T. AB - This work presents a new approach for high-resolution MRSI of the brain at 7 T in clinically feasible measurement times. Two major problems of MRSI are the long scan times for large matrix sizes and the possible spectral contamination by the transcranial lipid signal. We propose a combination of free induction decay (FID) MRSI with a short acquisition delay and acceleration via in-plane two-dimensional generalised autocalibrating partially parallel acquisition (2D-GRAPPA) with adiabatic double inversion recovery (IR)-based lipid suppression to allow robust high-resolution MRSI. We performed Bloch simulations to evaluate the magnetisation pathways of lipids and metabolites, and compared the results with phantom measurements. Acceleration factors in the range 2-25 were tested in a phantom. Five volunteers were scanned to verify the value of our MRSI method in vivo. GRAPPA artefacts that cause fold-in of transcranial lipids were suppressed via double IR, with a non-selective symmetric frequency sweep. The use of long, low-power inversion pulses (100 ms) reduced specific absorption rate requirements. The symmetric frequency sweep over both pulses provided good lipid suppression (>90%), in addition to a reduced loss in metabolite signal-to-noise ratio (SNR), compared with conventional IR suppression (52-70%). The metabolic mapping over the whole brain slice was not limited to a rectangular region of interest. 2D-GRAPPA provided acceleration up to a factor of nine for in vivo FID MRSI without a substantial increase in g-factors (<1.1). A 64 * 64 matrix can be acquired with a common repetition time of ~1.3 s in only 8 min without lipid artefacts caused by acceleration. Overall, we present a fast and robust MRSI method, using combined double IR fat suppression and 2D-GRAPPA acceleration, which may be used in (pre)clinical studies of the brain at 7 T. PMID- 26370783 TI - Dissecting pi-helices: sequence, structure and function. AB - A new procedure for the identification of regular secondary structures using a C(alpha) trace has identified 659 pi-helices in 3582 protein chains, solved at high resolution. Taking advantage of this significantly expanded database of pi helices, we have analysed the functional and structural roles of pi-helices and determined the position-wise amino acid propensity within and around them. These helices range from 5 to 18 residues in length with the average twist and rise being 85.2 +/- 7.2 degrees and 1.28 +/- 0.31 A, respectively. A total of 546 (~ 83%) out of 659 pi-helices occur in conjunction with alpha-helices, with 101 pi helices being interspersed between two alpha-helices. The majority of interspersed pi-helices were found to be conserved across a large number of structures within a protein family and produce a significant bend in the overall helical segment as well as local distortions in the neighbouring alpha-helices. The presence of a pi-helical fragment leads to appropriate orientation of the constituent residues, so as to facilitate favourable interactions and also help in proper folding of the protein chain. In addition to intra helical 6->1 N-H...O hydrogen bonds, pi-helices are also stabilized by several other non-bonded interactions. pi-Helices show distinct positional residue preferences, which are different from those of alpha-helices. PMID- 26370782 TI - Junctional and allele-specific residues are critical for MERS-CoV neutralization by an exceptionally potent germline-like antibody. AB - The MERS-CoV is an emerging virus, which already infected more than 1,300 humans with high (~36%) mortality. Here, we show that m336, an exceptionally potent human anti-MERS-CoV antibody, is almost germline with only one somatic mutation in the heavy chain. The structure of Fab m336 in complex with the MERS-CoV receptor-binding domain reveals that its IGHV1-69-derived heavy chain provides more than 85% binding surface and that its epitope almost completely overlaps with the receptor-binding site. Analysis of antibodies from 69 healthy humans suggests an important role of the V(D)J recombination-generated junctional and allele-specific residues for achieving high affinity of binding at such low levels of somatic hypermutation. Our results also have important implications for development of vaccine immunogens based on the newly identified m336 epitope as well as for elucidation of mechanisms of neutralization by m336-like antibodies and their elicitation in vivo. PMID- 26370784 TI - Digital imaging of colon tissue: method for evaluation of inflammation severity by spatial frequency features of the histological images. AB - BACKGROUND: The efficacy of histological analysis of colon sections used for evaluation of inflammation severity can be improved by means of digital imaging giving quantitative estimates of main diagnostic features. The aim of this study was to reveal most valuable diagnostic features reflecting inflammation severity in colon and elaborate the evaluation method for computer-aided diagnostics. METHODS: Tissue specimens from 24 BALB/c mice and 15 patients were included in the study. Chronic and acute colon inflammation in mice was induced by oral administration of dextran sulphate sodium (DSS) solution, while mice in the control group did not get DSS. Human samples of inflamed colon tissue were obtained from patients with ulcerative colitis (n = 6). Non-inflamed colon tissue of control subjects (n = 9) was obtained from patients with irritable bowel syndrome or functional obstipation. Analysis of morphological changes in mice and human colon mucosa was performed using 4-MUm haematoxylin-eosin (HE) sections. The features reflecting morphological changes in the images of colon mucosa were calculated by convolution of Gabor filter bank and array of pixel values. All features were generalized by calculating mean, histogram skewness and entropy of every image response. Principal component analysis was used to construct optimal representation of morphological changes. RESULTS: First principal component (PC1) was representing the major part of features variation (97 % in mice and 71 % in human specimens) and was selected as a measure of inflammation severity. Validation of new measure was performed by means of custom-made software realizing double blind comparison of differences in PC1 with expert's opinion about inflammation severity presented in two compared pictures. Overall accuracy of 80 % for mice and 67 % for human was reached. CONCLUSION: Principal component analysis of spatial frequency features of histological images may provide continuous scale estimation of inflammation severity of colon tissue. PMID- 26370785 TI - Sweet-potato washing revisited: 50th anniversary of the Primates article. PMID- 26370786 TI - The success of mechanical thrombectomy in acute ischaemic stroke is strictly dependent on ischaemic core size and time to treatment. PMID- 26370788 TI - There is Something About Grammatical Category in Chinese Visual Word Recognition. AB - The differential processing of nouns and verbs has been attributed to a combination of morphological, syntactic and semantic factors which are often intertwined with other general lexical properties. This study tested the noun verb difference with Chinese disyllabic words controlled on various lexical parameters. As Chinese words are free from inflectional morphology, any psychological distinction observed for nouns and verbs could be more convincingly attributed to syntactic factors echoing their linguistic distinction. Comparison among nouns, verbs and adjectives in lexical decision showed that nouns were processed faster than both verbs and adjectives, while the latter two classes, which are syntactically similar in Chinese, did not show any significant difference. The noun advantage over verbs was consistently found even when the classical frequency effect was duly considered. Thus the noun-verb distinction apparently surfaces at an early stage of lexical processing, and it is suggested that nouns may have a higher base activation level as they are linguistically less complex, which makes their access relatively more facilitated than verbs. PMID- 26370787 TI - Effect of ganglioside GT1b on the in vitro maturation of porcine oocytes and embryonic development. AB - Ganglioside is an acidic glycosphingolipid with sialic acids residues. This study was performed to investigate the effect and mechanism of ganglioside GT1b in porcine oocytes in the process of in vitro maturation (IVM) and preimplantation development. Metaphase II (MII) rates were significantly (P < 0.05) different between the control group and the 5 nM GT1b treatment group. Intracellular glutathione (GSH) levels in oocytes matured with 5 nM and 20 nM and GT1b decreased significantly (P < 0.05). The 10 nM group showed a significant (P < 0.05) decrease in intracellular reactive oxygen species (ROS) levels compared with the control group. Subsequently, the level of intracellular Ca(2+) in oocytes treated with different concentrations of GT1b was measured. Intracellular Ca(2+) was significantly (P < 0.05) increased with a higher concentration of GT1b in a dose-dependent manner. Real-time PCR was performed and showed that the expression of bradykinin 2 receptor (B2R) and calcium/calmodulin-dependent protein kinase II delta (CaMKIIdelta) in cumulus cells was significantly (P < 0.05) decreased in the 20 nM GT1b treatment group. Treatment with 5 nM GT1b significantly (P < 0.05) decreased the expression of CaMKIIdelta. In oocytes, treatment with 5 nM GT1b significantly (P < 0.05) decreased CaMKIIgamma and POU5F1 (POU domain, class 5, transcription factor 1). However, treatment with 20 nM GT1b significantly (P < 0.05) increased the expression of POU5F1. Finally, embryonic developmental data showed no significant differences in the two experiments (parthenogenesis and in vitro fertilization). In conclusion, the results of the present study indicated that GT1b plays an important role in increasing the nuclear maturation rate and decreasing the intracellular ROS levels during IVM. However, GT1b inhibited maturation of the cytoplasm by maintaining intracellular Ca(2+) in the process of oocyte maturation regardless of the cell cycle stage. Therefore, GT1b is thought to act on another mechanism that controls intracellular Ca(2+). PMID- 26370789 TI - Complete genome sequence of bellflower vein chlorosis virus, a novel putative member of the genus Waikavirus. AB - The complete genome sequence of a new virus isolated from a bellflower (Campanula takesimana) plant was determined. The genome of this virus is composed of monopartite single-stranded RNA of 11,649 nucleotides in length. BLAST searches of protein databases showed that the encoded polyprotein has a maximum amino acid sequence identity of 42% (with 99% coverage) to the polyprotein of the isolate Orissa of rice tungro spherical virus (RTSV; genus Waikavirus). Phylogenetic analysis strongly supports that the identified virus is a member of a new species of the genus Waikavirus. The name bellflower vein chlorosis virus (BVCV) is proposed for this new virus. PMID- 26370790 TI - Sequence and genome organization of papaya meleira virus infecting papaya in Brazil. AB - Papaya sticky disease ('meleira') was first observed in Brazil at the beginning of the 1980s. The disease is characterized by intense latex exudation from the fruit surface that becomes dark as it oxidizes, which makes it difficult to sell. The causal agent, which has been called papaya meleira virus (PMeV), has been identified as an isometric virus particle, approximately 50 nm in diameter, with a double-stranded RNA genome. Here, we report the first complete sequence and organization of the 8.7-kb viral dsRNA genome. Two ORFs coding for a putative coat protein and RNA-dependent RNA polymerase (RdRp) were predicted. In silico analysis revealed that the translated ORF2 contains the conserved domains characteristic of an RdRp protein (pfam02123:RdRP 4), which is a family that includes RdRps from members of the genera Luteovirus, Totivirus and Rotavirus. Evolutionary analysis with amino acid sequences with the RdRps from members of the family Totiviridae and some dsRNA viruses showed that PMeV RdRp did not root itself in any genus. PMID- 26370791 TI - Identification of a novel gammaherpesvirus associated with (muco)cutaneous lesions in harbour porpoises (Phocoena phocoena). AB - Herpesviruses infect a wide range of vertebrates, including toothed whales of the order Cetacea. One of the smallest toothed whales is the harbour porpoise (Phocoena phocoena), which is widespread in the coastal waters of the northern hemisphere, including the North Sea. Here, we describe the detection and phylogenetic analysis of a novel gammaherpesvirus associated with mucocutaneous and skin lesions in stranded harbour porpoises along the Dutch coast, tentatively designated phocoenid herpesvirus 1 (PhoHV1). Phylogenetically, PhoHV1 forms a monophyletic clade with all other gammaherpesviruses described in toothed whales (Odontoceti) to date, suggesting a common evolutionary origin. PMID- 26370792 TI - Taxonomy proposal for Old World monkey adenoviruses: characterisation of several non-human, non-ape primate adenovirus lineages. AB - A species classification regarding Old World monkey adenoviruses is proposed. We determined the nucleotide sequences of PCR-amplified fragments from the genes of the IVa2, DNA-dependent DNA polymerase, penton base, and hexon proteins from every simian adenovirus (SAdV) serotype that originated from Old World monkeys for which the full genome sequence had not yet been published. We confirmed that the majority of Old Word monkey SAdVs belong to two previously established species. Interestingly, one is the most recently established human AdV species, Human mastadenovirus G, which includes a single human virus, HAdV-52, as well as SAdV-1, -2, -7, -11, -12, and -15. The other approved species, Simian mastadenovirus A includes SAdV-3, -4, -6, -9, -10, -14, and -48. Several SAdVs (SAdV-5, -8, -49, -50) together with baboon AdV-1 and rhesus monkey AdV strains A1139, A1163, A1173, A1258, A1285, A1296, A1312, A1327 and A1335 have been proposed to be classified into an additional species, Simian mastadenovirus B. Another proposed species, Simian mastadenovirus C has been described for SAdV-19, baboon AdV-2/4 and -3. Our study revealed the existence of four additional AdV lineages. The corresponding new candidate species are Simian mastadenovirus D (for SAdV-13), Simian mastadenovirus E (for SAdV-16), Simian mastadenovirus F (for SAdV-17 and -18), and Simian mastadenovirus G (for SAdV-20). Several biological and genomic properties, such as the host origin, haemagglutination profile, number of fibre genes, and G+C content of the genome, strongly support this classification. Three SAdV strains originating from the American Type Culture Collection turned out to be mixtures of at least two virus types, either of the same species (SAdV-12 and -15 types from Human mastadenovirus G) or of two different species (SAdV-5 types from Simian mastadenovirus B and Human mastadenovirus G). PMID- 26370793 TI - Genomic Analysis of the Moderately Haloalkaliphilic Bacterium Oceanobacillus kimchii Strain X50T with Improved High-Quality Draft Genome Sequences. AB - Oceanobacillus kimchii is a member of the genus Oceanobacillus within the family Bacillaceae. Species of the Oceanobacillus possess moderate haloalkaliphilic features and originate from various alkali or salty environments. The haloalkaliphilic characteristics of Oceanobacillus advocate they may have possible uses in biotechnological and industrial applications, such as alkaline enzyme production and biodegradation. This study presents the draft genome sequence of O. kimchii X50(T) and its annotation. Furthermore, comparative genomic analysis of O. kimchii X 5 0(T) was performed with two previously reported Oceanobacillus genome sequences. The 3,822,411 base-pair genome contains 3,792 protein-coding genes and 80 RNA genes with an average G+C content of 35.18 mol%. The strain carried 67 and 13 predicted genes annotated with transport system and osmoregulation, respectively, which support the tolerance phenotype of the strain in high-alkali and high-salt environments. PMID- 26370794 TI - Construction of Recombinant Pichia pastoris Carrying a Constitutive AvBD9 Gene and Analysis of Its Activity. AB - Avian beta-defensin 9 (AvBD9) is a small cationic peptide consisting of 41 amino acids that plays a crucial rule in innate immunity and acquired immunity in chickens. Owing to its wide antibacterial spectrum, lack of a residue, and failure to induce bacterial drug resistance, AvBD9 is expected to become a substitute for conventional antibiotics in the livestock and poultry industries. Using the preferred codon of Pichia pastoris, the mature AvBD9 peptide was designed and synthesized, based on the sequence from GenBank. The P. pastoris constitutive expression vector pGHKalpha was used to construct a pGHKalpha-AvBD9 recombinant plasmid. Restriction enzyme digestion was performed using SacI and BglII to remove the ampicillin resistance gene, and the plasmid was electrotransformed into P. pastoris GS115. High-expression strains with G418 resistance were screened, and the culture supernatant was analyzed by Tricine-SDS PAGE and western blot assay to identify target bands of about 6 kDa. A concentrate of the supernatant containing AvBD9 was used for determination of antimicrobial activity. The supernatant concentrate was effective against Escherichia coli, Salmonella paratyphi, Salmonella pullorum, Pseudomonas aeruginosa, Enterococcus faecalis, and Enterobacter cloacae. The fermentation product of P. pastoris carrying the recombinant AvBD9 plasmid was adjusted to 1.0 * 10(8) CFU/ml and added to the drinking water of white feather broilers at different concentrations. The daily average weight gain and immune organ indices in broilers older than 7 days were significantly improved by the AvBD9 treatment. PMID- 26370795 TI - Growth Period Effects on the Protective Properties of Aloe vera Against t-BHP Induced Oxidative Stress in Chang Cells. AB - Aloe vera has been used in traditional medicine for the therapy of a variety of disorders, such as wounds and burns. However, few studies have examined the antioxidant capacities of A. vera plants during different growth periods. In order to investigate the effects of growth on antioxidant activity, A. vera was prepared from 2-, 4-, 6-, 8-, and 12-month-old aloe. The extracts from 6-month old A. vera showed the highest contents of flavonoids (9.750 mg catechin equivalent/g extract) and polyphenols (23.375 mg gallic acid equivalent/g extract) and the highest ferric reducing antioxidant power (0.047 mM ferrous sulfate equivalent/mg extract). The extract from 6-month-old A. vera exhibited the highest free radical scavenging potential, and the lowest IC50 values were found for 2,2-diphenyl-1-picrylhydrazyl (0.26 mg/ml) and alkyl radicals (0.50 mg/ml). In addition, the extract from 6-month-old A. vera showed the greatest effects on cell viability in normal liver cells. Based on these findings, the extract from 6-month-old A. vera was examined further in order to determine its protective potential against tert-butyl hydroperoxide (t-BHP)-induced oxidative stress. The extract from 6-monthold A. vera at a concentration of 0.25 mg/ml showed the highest protective activity against t-BHP-induced reactive oxygen species production. These findings suggested that harvesting regimens were critical in the regulation of effects of the bioactive potential of A. vera on antioxidant activity. PMID- 26370796 TI - Evaluation of Time-Temperature Integrators (TTIs) with Microorganism-Entrapped Microbeads Produced Using Homogenization and SPG Membrane Emulsification Techniques. AB - A comparative study was conducted to evaluate precision and accuracy in controlling the temperature dependence of encapsulated microbial time-temperature integrators (TTIs) developed using two different emulsification techniques. Weissela cibaria CIFP 009 cells, immobilized within 2% Na-alginate gel microbeads using homogenization (5,000, 7,000, and 10,000 rpm) and Shirasu porous glass (SPG) membrane technologies (10 MUm), were applied to microbial TTIs. The prepared micobeads were characterized with respect to their size, size distribution, shape and morphology, entrapment efficiency, and bead production yield. Additionally, fermentation process parameters including growth rate were investigated. The TTI responses (changes in pH and titratable acidity (TA)) were evaluated as a function of temperature (20 degrees C, 25 degrees C, and 30 degrees C). In comparison with conventional methods, SPG membrane technology was able not only to produce highly uniform, small-sized beads with the narrowest size distribution, but also the bead production yield was found to be nearly 3.0 to 4.5 times higher. However, among the TTIs produced using the homogenization technique, poor linearity (R(2)) in terms of TA was observed for the 5,000 and 7,000 rpm treatments. Consequently, microbeads produced by the SPG membrane and by homogenization at 10,000 rpm were selected for adjusting the temperature dependence. The Ea values of TTIs containing 0.5, 1.0, and 1.5 g microbeads, prepared by SPG membrane and conventional methods, were estimated to be 86.0, 83.5, and 76.6 kJ/mol, and 85.5, 73.5, and 62.2 kJ/mol, respectively. Therefore, microbial TTIs developed using SPG membrane technology are much more efficient in controlling temperature dependence. PMID- 26370797 TI - Sonicated Protein Fractions of Mycoplasma hyopneumoniae Induce Inflammatory Responses and Differential Gene Expression in a Murine Alveolar Macrophage Cell Line. AB - Mycoplasma hyopneumoniae is known to cause porcine enzootic pneumonia (EP), an important disease in swine production. The objective of this study was to examine the effects of sonicated protein fractions of M. hyopneumoniae on inflammatory response and gene expression in the murine alveolar macrophage MH-S cell line. The effects of sonicated protein fractions and intact M. hyopneumoniae on the gene expression of cytokines and iNOS were assessed using RT-PCR. The Annealing Control Primer (ACP)-based PCR method was used to screen differentially expressed genes. Increased transcription of interleukin (IL)-1beta, IL-6, tumor necrosis factor (TNF)-alpha, COX-2, and iNOS mRNA was observed after exposure to the supernatant (SPT), precipitant (PPT), and intact M. hyopneumoniae protein. A time dependent analysis of the mRNA expression revealed an upregulation after 4 h for IL-6 and iNOS and after 12 h for IL-1beta and TNF-alpha, for both SPT and PPT; the fold change in COX-2 expression was less. A dose- and time-dependent correlation was observed in nitrite (NO) production for both protein fractions; however, there was no significant difference between the effects of the two protein fractions. In a differential gene analysis, PCR revealed differential expression for nine gene bands after 3 h of stimulation - only one gene was downregulated, while the remaining eight were upregulated. The results of this study provide insights that help improve our understanding of the mechanisms underlying the pathogenesis of and macrophage defenses against M. hyopneumoniae assault, and suggest targets for future studies on therapeutic interventions for M. hyopneumoniae infections. PMID- 26370799 TI - Anti-Metastasis Effects of Ginsenoside Rg3 in B16F10 Cells. AB - Ginsenoside Rg3 is a bioactive ginseng constituent that has been reported to have diverse pathological and physiological effects, including anti-inflammatory and anti-metastatic activities. Metastasis is one of the most important factors involved in patients with melanoma. However, the molecular mechanism underlying the anti-metastatic activities of Rg3 in malignant melanoma cancer has not been fully elucidated. In this study, we have evaluated that Rg3 effectively inhibits metastasis of B16F10 melanoma cancer cells. We found that Rg3 significantly suppresses the migration, invasion, wound healing, and colony-forming abilities of B16F10 cells in a dose-dependent manner. Mechanistically, we demonstrate that Rg3 suppresses B16F10 cell metastasis by inhibiting MMP-13 expression. These results indicate that Rg3 suppresses the metastasis of B16F10 mouse melanoma cancer cells via MMP-13 regulation. Importantly, MMP-13 downregulation may influence the migration and invasion capabilities of melanoma cells and has been correlated with melanoma progression. Therefore, Rg3 is a potential therapeutic candidate that could be used to treat patients with metastatic melanoma. PMID- 26370798 TI - Enzymatic Manufacture of Deoxythymidine-5'-Triphosphate with Permeable Intact Cells of E. coli Coexpressing Thymidylate Kinase and Acetate Kinase. AB - A one-pot process of enzymatic synthesis of deoxythymidine-5'-triphosphate (5' dTTP) employing whole cells of recombinant Escherichia coli coexpressing thymidylate kinase (TMKase) and acetate kinase (ACKase) was developed. Genes tmk and ack from E. coli were cloned and inserted into pET28a(+), and then transduced into E. coli BL21 (DE3) to form recombinant strain pTA in which TMKase and ACKase were simultaneously overexpressed. It was found that the relative residual specific activities of TMKase and ACKase, in pTA pretreated with 20 mM ethylene diamine tetraacetic acid (EDTA) at 25 degrees C for 30 min, were 94% and 96%, respectively. The yield of 5'-dTTP reached above 94% from 5 mM deoxythymidine 5' monophosphate (5'-dTMP) and 15 mM acetyl phosphate catalyzed with intact cells of pTA pretreated with EDTA. The process was so effective that only 0.125 mM adenosine-5'- triphosphate was sufficient to deliver the phosphate group from acetyl phosphate to dTMP and dTDP. PMID- 26370800 TI - Characterization of an Alkaline Family I.4 Lipase from Bacillus sp. W130-35 Isolated from a Tidal Mud Flat with Broad Substrate Specificity. AB - A gene encoding lipolytic enzyme, lip7-3, was isolated from Bacillus sp. W130-35 isolated from a tidal mud flat. The gene encoded a protein of 215 amino acids with a signal peptide composed of 34 amino acid residues. Lip7-3 belonged to the family I.4 lipase and showed its maximal activity at pH 9.0 and 60 degrees C. Its activity increased in the presence of 30% methanol and, remarkably, increased as well to 154.6% in the presence of Ca(2+). Lip7-3 preferred pnitrophenyl octanoate (C8) as a substrate and exhibited broad specificity for short- to longchain fatty acid esters. Additionally, Lip7-3 showed a low degree of enantioselectivity for an S-enantiomer (e.g., (S)-methyl-3-hydroxy-2-methylpropionate). It efficiently hydrolyzed glyceryl tributyrate, but did not hydrolyze glyceryl trioleate, fish oil, or olive oil. Its substrate specificity and activation by the solvent might offer a merit to the biotechnological enzyme applications like transesterification in the production of biodiesel. PMID- 26370801 TI - Effect of Low Salt Concentrations on Microbial Changes During Kimchi Fermentation Monitored by PCR-DGGE and Their Sensory Acceptance. AB - Various salt concentrations (1.0%, 1.3%, 1.6%, 1.9%, and 2.1% labeled as sample A, B, C, D, and E, respectively) were investigated for microbial diversity, identification of Lactic Acid Bacteria (LAB) in salted kimchi cabbage, prepared under laboratory conditions. These samples were stored at 4 degrees C for 5 weeks in proper aluminum-metalized pouch packaging with calcium hydroxide gas absorber. A culture-independent method known as polymerase chain reaction - denaturing gradient gel electrophoresis was carried out to identify LAB distributions among various salt concentration samples that had identified 2 Weissella (W. confusa and W. soli), 1 Lactobacillus (Lb. sakei), and 3 Leuconostoc (Lc. mesenteroides, Lc. lactis, and Lc. gelidum) in the overall kimchi samples. The pH, titratable acidity, viable cell counts, and coliform counts were not affected by salt variations. In order to assess sensory acceptance, the conducted sensory evaluation using a 9-point hedonic scale had revealed that samples with 1.3% salt concentration (lower than the manufacturer's regular salt concentration) was more preferred, indicating that the use of 1.3% salt concentration was acceptable in normal kimchi fermentation for its quality and safety. Despite similarities in pH, titratable acidity, viable cell counts, coliform counts, and LAB distributions among the various salt concentrations of kimchi samples, the sample with 1.3% salt concentration was shown to be the most preferred, indicating that this salt concentration was suitable in kimchi production in order to reduce salt intake through kimchi consumptions. PMID- 26370802 TI - Characterization of Two GAS1 Genes and Their Effects on Expression and Secretion of Heterologous Protein Xylanase B in Kluyveromyces lactis. AB - beta-1,3-glucanosyltransferases play essential roles in cell wall biosynthesis in yeast. Kluyveromyces lactis has six putative beta-1,3-glucanosyltransferase genes. KlGAS1-1 and KlGAS1-2 are homologs of Saccharomyces cerevisiae gene GAS1. RT-qPCR indicated the transcription level of KlGAS1-1 was significantly reduced while heterologous protein (thermostable xylanase B) secretion was enhanced during medium optimization. To evaluate if these two events were related, and to improve xylanase B secretion in K. lactis, we constructed KlGAS1-1 and KlGAS1-2 single deletion strains and double deletion strain, respectively. KlGAS1-1 gene deletion resulted in the highest xylanase B activity among the three mutants. Only the double deletion strain showed morphology similar to that of the GAS1 deletion mutant in S. cerevisiae. The two single deletion strains differed in terms of cell wall thickness and xylanase B secretion. Transcription levels of beta-1,3-glucanosyltransferase genes and genes related to protein secretion and transport were assayed. The beta-1,3-glucanosyltransferase genes displayed transcription complementation in the cell wall synthesis process. KlGAS1-1 and KlGAS1-2 affected transcription levels of secretion- and transport-related genes. Differences in protein secretion ratio among the three deletion strains were associated with changes of transcription levels of secretion- and transport related genes. Our findings indicate that KlGAS1-1 deletion is an effective tool for enhancing industrial-scale heterologous protein secretion in K. lactis. PMID- 26370803 TI - The Site-Directed A184S Mutation in the HTH Domain of the Global Regulator IrrE Enhances Deinococcus radiodurans R1 Tolerance to UV Radiation and MMC Shock. AB - IrrE is a highly conserved global regulator in the Deinococcus genus and contributes to survival from high doses of UV radiation, ionizing radiation, and desiccation. Drad-IrrE and Dgob-IrrE from Deinococcus radiodurans and Deinococcus gobiensis I-0 each share 66% sequence identity. However, Dgob-IrrE showed a stronger protection phenotype against UV radiation than Drad- IrrE in the D. radiodurans irrE-deletion mutant (DeltairrE), which may be due to amino acid residues differences around the DNA-binding HTH domain. Site-directed mutagenesis was used to generate a Drad-IrrE A184S single mutant, which has been characterized and compared with the DeltairrE mutant complemented strain with Drad-irrE, designated DeltairrE-E. The effects of the A184S mutation following UV radiation and mitomycin C (MMC) shock were determined. The A184S mutant displayed significantly increased resistance to UV radiation and MMC shock. The corresponding A184 site in Dgob-IrrE was inversely mutated, generating the S131A mutant, which exhibited a loss of resistance against UV radiation, MMC shock, and desiccation. qPCR analysis revealed that critical genes in the DNA repair system, such as recA, pprA, uvrA, and ddrB, were remarkably induced after UV radiation and MMC shock in the DeltairrE-IE and A184S mutants. These data suggested that A184S improves the ability against UV radiation and MMC shock, providing new insights into the modification of IrrE. We speculated that the serine residue may determine the efficiency of DNA binding, leading to the increased expression of IrrE-dependent genes important for protection against DNA damage. PMID- 26370804 TI - Specific and Sensitive Detection of the Pear Scab Fungus Venturia nashicola by SYBR Green Real-Time PCR. AB - A new improved PCR method has been developed for the rapid, reliable, and sensitive detection of Venturia nashicola, a destructive pathogen of scab disease in Japanese pear. The translation elongation factor-1 alpha gene-derived PCR primers specifically amplified a 257-bp-sized DNA band of the target gene from the genomic DNA of V. nashicola. No amplicon was produced from the genomic DNA of other Venturia spp. and reference fungal species tested. With the high detection limit of 10 fg DNA content, our real-time method could be used for the quarantine inspection and field monitoring of V. nashicola. PMID- 26370807 TI - Persistent organic pollutants (POPs): a global issue, a global challenge. PMID- 26370805 TI - Oral supplementation of diabetic mice with propolis restores the proliferation capacity and chemotaxis of B and T lymphocytes towards CCL21 and CXCL12 by modulating the lipid profile, the pro-inflammatory cytokine levels and oxidative stress. AB - BACKGROUND: Type 1 diabetes mellitus (T1D) is a chronic autoimmune disease caused by the selective destruction of pancreatic beta cells, followed by hyperglycemia, oxidative stress and the subsequent extensive impairment of immune cell functions, a phenomenon responsible for the development of chronic diabetic complications. Propolis, a natural bee product that is extensively used in foods and beverages, significantly benefits human health. Specifically, propolis exerts antioxidant, anti-inflammatory and analgesic effects that may improve diabetic complications. To further elucidate the potential benefits of propolis, the present study investigated the effect of dietary supplementation with propolis on the plasma cytokine profiles, free radical levels, lipid profile and lymphocyte proliferation and chemotaxis in a streptozotocin (STZ)-induced type I diabetic mouse model. METHODS: Thirty male mice were equally distributed into 3 experimental groups: group 1, non-diabetic control mice; group 2, diabetic mice; and group 3, diabetic mice supplemented daily with an ethanol-soluble derivative of propolis (100 mg/kg body weight) for 1 month. RESULTS: First, the induction of diabetes in mice was associated with hyperglycemia and significant decreases in the insulin level and the lymphocyte count. In this context, diabetic mice exhibited severe diabetic complications, as demonstrated by a significant decrease in the levels of IL-2, IL-4 and IL-7, prolonged elevation of the levels of pro-inflammatory cytokines (IL-1beta, IL-6 and TNF-alpha) and reactive oxygen species (ROS) and altered lipid profiles compared with control non-diabetic mice. Moreover, antigen stimulation of B and T lymphocytes markedly reduced the proliferative capacity and chemotaxis of these cells towards CCL21 and CXCL12 in diabetic mice compared with control mice. Interestingly, compared with diabetes induction alone, treatment of diabetic mice with propolis significantly restored the plasma cytokine and ROS levels and the lipid profile to nearly normal levels. Most importantly, compared with untreated diabetic mice, diabetic mice treated with propolis exhibited significantly enhanced lymphocyte proliferation and chemotaxis towards CCL21 and CXCL12. CONCLUSION: Our findings reveal the potential immuno-modulatory effects of propolis, which acts as a natural antioxidant to enhance the function of immune cells during diabetes. PMID- 26370806 TI - Sun Protection Habits and Attitudes Among Healthcare Personnel in a Mediterranean Population. AB - Health professionals are key agents in healthcare promotion. In the field of skin cancer, they play a crucial role in the development of prevention strategies in the community. This paper aims to describe the sun exposure attitudes and habits of public healthcare professionals in the western Costa del Sol (Spain). A cross sectional descriptive study was conducted in the Costa del Sol healthcare district to analyse sun exposure and protection practices and habits, and attitudes to tanning and sun protection. The respondents, all healthcare personnel in various professional categories and workplace situations, were asked to complete a self-administered questionnaire. Six hundred forty-three workers in the Costa del Sol healthcare district took part in the study. Of these participants, 450 were healthcare professionals. Of the 450 health professionals, 226 (50.2 %) were nurses or auxiliary nursing staff, and the remaining 224 were doctors. These two groups presented differences regarding habits of sun exposure: 15.3 % of the doctors went to the beach at least 30 days a year, compared to 30.9 % of the nurses (p < 0.001). With respect to workplace situation, there were differences (p < 0.001) between the sunburn events reported by healthcare staff who worked in hospitals (52.4 %) compared to those working in primary healthcare (30.4 %); comparable differences were found with respect to attitudes toward the use of sunscreen creams (p = 0.014). This study identifies two distinct subgroups within healthcare personnel: on one hand, primary healthcare professionals, who are key agents for future policy strategies, and on the other, specialist healthcare professionals, who are more likely to suffer sunburn events and therefore toward whom strategies should be addressed to encourage them to change their sun exposure attitudes and habits and sun protection practices. PMID- 26370808 TI - Pesticides applications assessment in banana crop conditions: a methodological approach. PMID- 26370809 TI - Ecological implication of variation in the secondary metabolites in Parmelioid lichens with respect to altitude. AB - Lichens are known to synthesize a variety of secondary metabolites having multifunctional activity in response to external environmental condition. Two common lichen extrolites, atranorin and salazinic acid, are known to afford antioxidant as well as photoprotectant nature depending on the abiotic/biotic stress. The present investigation aims to study the influence of altitudinal gradient on the quantitative profile of atranorin and salazinic acid in three lichen species, Bulbothrix setschwanensis (Zahlbr.) Hale, Everniastrum cirrhatum (Fr.) Hale and Parmotrema reticulatum (Taylor) Choisy, Parmeliaceae using liquid chromatography-mass spectrometry (LC-MS/MS) technique. Samples were collected from high-altitude area, usually considered as non-polluted sites of Garhwal Himalaya. Characterization and quantification of the lichen substances in samples were carried out comparing with the standards of atranorin and salazinic acid. Results indicated significant variation in the chemical content with the rising altitude. All the three lichen species showed higher quantities of chemical substances with the altitudinal rise, while among the three lichen species, E. cirrhatum showed the highest quantity of total lichen compounds. The higher abundance and frequency of E. cirrhatum with increasing altitude as compared to B. setschwanensis and P. reticulatum may be attributed due to the presence of higher quantity of photoprotecting/antioxidant chemicals especially salazinic acid. Thus, the present study shows the prominent role of secondary metabolite in wider ecological distribution of Parmelioid lichens at higher altitudes. PMID- 26370810 TI - Benthic ecosystem functioning in the severely contaminated Mar Piccolo of Taranto (Ionian Sea, Italy): focus on heterotrophic pathways. AB - The benthic ecosystem functioning is a rarely applied holistic approach that integrates the main chemical and biological features of the benthic domain with the key processes responsible for the flux of energy and C through the system. For the first time, such conceptual model, with an emphasis on the heterotrophic pathways, has been applied to the sediments at four stations within one of the most polluted coastal areas in Italy: the Mar Piccolo of Taranto. The functioning of the benthic ecosystem was different according to the investigated site. Nearby the military arsenal, i.e., the main source of organic contaminants and heavy metals, the system seemed inhibited at all the investigated structural and functional levels. Slow microbial processes of C reworking together with very limited densities of benthic fauna suggested a modest transfer of C both into a solid microbial loop and to the higher trophic levels. On the other hand, the ingression of marine water through the "Navigabile" channel seemed to stimulate the organic matter degradation and, consequently, the proliferation of meiofauna and macrofauna. In the innermost part of the basin, the system functioning, to some extent, is less impacted by contaminants and more influenced by mussel farms. The organic matter produced by these bivalves fueled faster C reworking by benthic prokaryotes and enhanced the proliferation of filter feeders. PMID- 26370811 TI - Aluminum uptake and migration from the soil compartment into Betula pendula for two different environments: a polluted and environmentally protected area of Poland. AB - This paper presents the impact of soil contamination on aluminum (Al) concentrations in plant parts of Betula pendula and a possible way of migration and transformation of Al in the soil-root-stem-twig-leaf system. A new procedure of Al fractionation based on extraction in water phase was applied to obtain and measure the most available forms of Al in soils and B. pendula samples. In addition, total Al content was determined in biological samples and pseudo total Al content in soil samples collected under plant saplings, using atomic absorption spectrometry with flame atomization. A number of relations concerning the occurrence of Al and Ca in soils and plant parts of B. pendula (tap roots, lateral roots, stem, twigs, and leaves) were observed. Based on the research findings, the mechanism of Al migration from soil to the leaves of B. pendula can be presented. It was found that aluminum uptake may be limited in roots by high calcium concentration. The application of a new procedure based on the simple sequential extraction of water-soluble fractions (the most available and exchangeable fractions of Al) can be used as an effective tool for the estimation of aluminum toxicity in soils and plants. PMID- 26370812 TI - Degradability of chlorophenols using ferrate(VI) in contaminated groundwater. AB - The production and use of chlorophenolic compounds in industry has led to the introduction of many xenobiotics, among them chlorophenols (CPs), into the environment. Five CPs are listed in the priority pollutant list of the U.S. EPA, with pentachlorophenol (PCP) even being proposed for listing under the Stockholm Convention as a persistent organic pollutant (POP). A green procedure for degrading such pollutants is greatly needed. The use of ferrate could be such a process. This paper studies the degradation of CPs (with an emphasis on PCP) in the presence of ferrate both in a spiked demineralized water system as well as in real contaminated groundwater. Results proved that ferrate was able to completely remove PCP from both water systems. Investigation of the effect of ferrate purity showed that even less pure and thus much cheaper ferrate was applicable. However, with decreasing ferrate purity, the degradability of CPs may be lower. PMID- 26370813 TI - Silicon alleviates Cd stress of wheat seedlings (Triticum turgidum L. cv. Claudio) grown in hydroponics. AB - We investigated the potential role of silicon in improving tolerance and decreasing cadmium (Cd) toxicity in durum wheat (Triticum turgidum L. durum) either through a reduced Cd uptake or exclusion/sequestration in non-metabolic tissues. For this, plants were grown in hydroponic conditions for 10 days either in presence or absence of 1 mM Si and for 11 additional days in various Cd concentrations (0, 0.5, 5.0 and 50 MUM). After harvesting, morphological and physiological parameters as well as elemental concentrations were recorded. Cadmium caused reduction in growth parameters, photosynthetic pigments and mineral nutrient concentrations both in shoots and roots. Shoot and root contents of malate, citrate and aconitate increased, while contents of phosphate, nitrate and sulphate decreased with increasing Cd concentrations in plants. Addition of Si to the nutrient solution mitigated these adverse effects: Cd concentration in shoots decreased while concentration of Cd adsorbed at the root cell apoplasmic level increased together with Zn uptake by roots. Overall, total Cd uptake decreased in presence of Si. There was no co-localisation of Cd and Si either at the shoot or at the root levels. No Cd was detected in leaf phytoliths. In roots, Cd was mainly detected in the cortical parenchyma and Si at the endodermis level, while analysis of the outer thin root surface of the plants grown in the 50 MUM Cd + 1 mM Si treatment highlighted non-homogeneous Cd and Si enrichments. These data strongly suggest the existence of a root localised protection mechanism consisting in armoring the root surface by Si- and Cd-bearing compounds and in limiting root-shoot translocation. PMID- 26370814 TI - The accumulation of heavy metals in agricultural land and the associated potential ecological risks in Shenzhen, China. AB - Accumulation of heavy metals in agricultural land and their ecological risks are key issues in soil security studies. This study investigated the concentrations of six heavy metals--copper (Cu), zinc (Zn), lead (Pb), nickel (Ni), and chromium (Cr) in Shenzhen's agricultural lands and examined the potential hazards and possible sources of these metals. Eighty-two samples from agricultural topsoil were collected. Potential ecological risk index was used to calculate the potential risk of heavy metals. Principal component analysis (PCA) was applied to explore pollution sources of the metals. Finally, Kriging was used to predict the spatial distribution of the metals' potential ecological risks. The concentrations of the heavy metals were higher than their background values. Most of them presented little potential ecological risk, except for the heavy metal cadmium (Cd). Four districts (Longgang, Longhua, Pingshan, and Dapeng) exhibited some degree of potential risk, which tended to have more industries and road networks. Three major sources of heavy metals included geochemical processes, industrial pollutants, and traffic pollution. The heavy metal Cd was the main contributor to the pollution in agricultural land during the study period. It also poses the potential hazard for the future. High potential risk is closely related to industrial pollution and transportation. Since the 1980s, the sources of heavy metals have evolved from parent rock weathering, erosion, degradation of organics, and mineralization to human disturbances resulting in chemical changes in the soil. PMID- 26370815 TI - Cadmium re-distribution from pod and root zones and accumulation by peanut (Arachis hypogaea L.). AB - Peanut (Arachis hypogaea L.) genotypes may differ greatly with regard to cadmium (Cd) accumulation, but the underlying mechanisms remain unclear. To determine the key factors that may contribute to Cd re-distribution and accumulation in peanut genotypes with different Cd accumulating patterns, a split-pot soil experiment was conducted with three common Chinese peanut cultivars (Fenghua-6, Huayu-20, and Huayu-23). The growth medium was separated into pod and root zones with varied Cd concentrations in each zone to determine the re-distribution of Cd after it is taken up via different routes. The peanut cultivars were divided into two groups based on Cd translocation efficiency as follows: (1) high internal Cd translocation efficiency cultivar (Fenghua-6) and (2) low internal Cd translocation efficiency cultivars (Huayu-20 and Huayu-23). Compared with Fenghua 6, low Cd translocation cultivars Huayu-20 and Huayu-23 showed higher biomass production, especially in stems and leaves, leading to dilution of metal concentrations. Results also showed that Cd concentration in roots increased significantly with increasing Cd concentrations in soils when Cd was applied in the root zone. However, there were no significant differences in the root Cd concentrations between different pod zone Cd treatments and the control, suggesting that root uptake, rather than pod uptake, is responsible for Cd accumulation in the roots of peanuts. Significant differences of Cd distribution were observed between pod and root zone Cd exposure treatments. The three peanut cultivars revealed higher kernel over total Cd fractions for pod than for root zone Cd exposure if only extra applied Cd was considered. This suggests that uptake through peg and pod shell might, at least partially, be responsible for the variation in Cd re-distribution and accumulation among peanut cultivars. Cd uptake by plants via two routes (i.e., via roots and via pegs and pods, respectively) and internal Cd translocation appear to be important mechanisms in determining Cd accumulation in the kernels of peanuts. PMID- 26370816 TI - Isolation, purification, and identification of antialgal substances in green alga Ulva prolifera for antialgal activity against the common harmful red tide microalgae. AB - Ten compounds (1~10) were successfully isolated from green algae Ulva prolifera through the combination of silica gel column chromatography, Sephadex LH-20 column chromatography and repeated preparative thin-layer chromatography. These ten compounds showed antialgal activity against red tide microalgae. Among them, compounds 3, 6, and 7 showed stronger antialgal activity against red tide microalgae. Furthermore, their structure was identified on the basis of spectroscopic data. There are three glycoglycerolipids: 1-O-octadecanoic acid-3-O beta-D-galactopyranosyl glycerol (2), 1-O-palmitoyl-3-O-beta-D-galactopyranosyl glycerol (4), and 1-O-palmitoyl-2-O-oleoyl-3-O-beta-D-galactopyranosyl glycerol (5); two monoglycerides: glycerol monopalmitate (1), 9-hexadecenoic acid, 2,3 dihydroxypropyl ester (3); two terpenoids: loliolide (6) and lsololiolide (7); one lipid-soluble pigments: zeaxanthin (8); one sterol: cholest-5-en-3-ol (9); and one alkaloid: pyrrolopiperazine-2,5-dione (10). These compounds were isolated from U. prolifera for the first time, and compounds 2, 3, 5, and 8 were isolated from marine macroalgae for the first time. PMID- 26370817 TI - Novel approach for extinguishing large-scale coal fires using gas-liquid foams in open pit mines. AB - Coal fires are a serious threat to the workers' security and safe production in open pit mines. The coal fire source is hidden and innumerable, and the large area cavity is prevalent in the coal seam after the coal burned, causing the conventional extinguishment technology difficult to work. Foams are considered as an efficient means of fire extinguishment in these large-scale workplaces. A noble foam preparation method is introduced, and an original design of cavitation jet device is proposed to add foaming agent stably. The jet cavitation occurs when the water flow rate and pressure ratio reach specified values. Through self building foaming system, the high performance foams are produced and then infused into the blast drilling holes at a large flow. Without complicated operation, this system is found to be very suitable for extinguishing large-scale coal fires. Field application shows that foam generation adopting the proposed key technology makes a good fire extinguishment effect. The temperature reduction using foams is 6-7 times higher than water, and CO concentration is reduced from 9.43 to 0.0920/00 in the drilling hole. The coal fires are controlled successfully in open pit mines, ensuring the normal production as well as the security of personnel and equipment. PMID- 26370818 TI - Investigation of heavy metal (Cu, Pb, Cd, and Cr) stabilization in river sediment by nano-zero-valent iron/activated carbon composite. AB - Nano-zero-valent iron/activated carbon (nZVI/AC) composite was evaluated for its effectiveness in the stabilization of Cu, Pb, Cd, and Cr in dredged river sediment. Synthetic precipitation leaching procedure (SPLP) and toxicity characteristic leaching procedure (TCLP) were adopted to compare the effects of nZVI/AC dosage, particle size, time duration, and temperature on heavy metal leachability. The results show that leachability dropped considerably with the addition of nZVI/AC and powdered particles in the size of 0.075-0.18 mm was more effective in stabilization than granular ones. Stabilization effect was stable in long-term and robust against changes in temperature. Tessier sequential extraction revealed that heavy metals were associated with solid particle, inorganic or organic matters in sediment. The addition of nZVI/AC was able to convert relatively weakly bound heavy metals into more strongly bound species and thus reduce the bioavailability and toxicity. Also, the standard potential of heavy metals may decide the mechanism of stabilization process. PMID- 26370819 TI - Oxidation of elemental mercury by modified spent TiO2-based SCR-DeNOx catalysts in simulated coal-fired flue gas. AB - In order to reduce the costs, the recycle of spent TiO2-based SCR-DeNOx catalysts were employed as a potential catalytic support material for elemental mercury (Hg(0)) oxidation in simulated coal-fired flue gas. The catalytic mechanism for simultaneous removal of Hg(0) and NO was also investigated. The catalysts were characterized by Brunauer-Emmett-Teller (BET), scanning electron microscope (SEM), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS) method. Results indicated that spent TiO2-based SCR-DeNOx catalyst supported Ce Mn mixed oxides catalyst (CeMn/SCR1) was highly active for Hg(0) oxidation at low temperatures. The Ce1.00Mn/SCR1 performed the best catalytic activities, and approximately 92.80% mercury oxidation efficiency was obtained at 150 degrees C. The inhibition effect of NH3 on Hg(0) oxidation was confirmed in that NH3 consumed the surface oxygen. Moreover, H2O inhibited Hg(0) oxidation while SO2 had a promotional effect with the aid of O2. The XPS results illustrated that the surface oxygen was responsible for Hg(0) oxidation and NO conversion. Besides, the Hg(0) oxidation and NO conversion were thought to be aided by synergistic effect between the manganese and cerium oxides. PMID- 26370820 TI - The study on the evaluation of the pollution control situation of the sewage systems in the counties and cities of Taiwan by applying the VIKOR method. AB - Currently, the pollution control situation of the sewage systems across Taiwan can be divided into the two major sewage systems, namely, industrial area sewage and public community sewage. When the counties and cities of Taiwan cannot effectively control the sewage pollution situation, ecological pollution of the environment and personal health damage would result. Therefore, evaluating the pollution control situation of the sewage systems can help the environmental protection authorities developing strategies for the pollution control of the sewage systems in the future. In this study, the Vise Kriterijumska Optimizacija I Kompromisno Resenje (VIKOR) method was applied to evaluate the pollution control situation of the sewage systems. The water sample test qualification rate, the emission permit issuance rate, and the staff setting rate of the dedicated wastewater treatment company were used as the pollution control evaluation indexes. According to the results, the use of the VIKOR method to evaluate the pollution control situation of the sewage systems is effective. In cities and counties in Taiwan, public community sewage systems, dedicated to pollution control case, the public community should be actively coached in emission control technology to upgrade sewage capacity, the issuance of discharge permits, and the staff setting rate of the dedicated wastewater treatment, to improve public community sewage pollution control system capabilities. In Taiwan, the industrial area sewage systems, dedicated to pollution control situations, must pay attention to business units in raw materials, spare part inventory, and machine supplier of choice, and we must choose to meet environmental supply chain of green suppliers, which would be effective in reducing effluent produce and improve water sample test qualification rate. The VIKOR value of Yilan County is 1.0000, which is the worst in the pollution control of all the industrial area sewage systems, followed by Taoyuan County (0.2253) and Kaohsiung City (0.1334). Other cities and counties of Taiwan have good performance in the pollution control of the industrial area sewage systems. The VIKOR value of Kinmen County is 1.0000, which is the worst pollution control among the all public community sewage systems, followed by Hsinchu County (0.7458) and New Taipei City (0.5527). Among the cities and counties with good pollution control of the public community sewage systems, the best is Chiayi County (0.0000), followed by Kaohsiung City (0.0159) and Hsinchu City (0.0352). Chiayi County is a good performance compromise between all VIKOR values (0.0000), whether in industrial or public community area pollution control sewage systems. Yilan County industrial pollution control has the poorest performance of all the industrial area sewage systems in Taiwan, but in the public community, it ranked as fourth place of all the public community area sewage systems in Taiwan. The VIKOR method proposed in this study can effectively evaluate the pollution control situation of the sewage systems, and serve as a reference for the environmental protection authorities in developing the strategies for the pollution control of the sewage systems. PMID- 26370821 TI - New reports from the NIOSH health hazard evaluation program. PMID- 26370822 TI - Exposure to airborne asbestos in thermal power plants in Mongolia. PMID- 26370823 TI - Impact of intravenous fluid composition on outcomes in patients with systemic inflammatory response syndrome. AB - INTRODUCTION: Intravenous (IV) fluids may be associated with complications not often attributed to fluid type. Fluids with high chloride concentrations such as 0.9 % saline have been associated with adverse outcomes in surgery and critical care. Understanding the association between fluid type and outcomes in general hospitalized patients may inform selection of fluid type in clinical practice. We sought to determine if the type of IV fluid administered to patients with systemic inflammatory response syndrome (SIRS) is associated with outcome. METHODS: This was a propensity-matched cohort study in hospitalized patients receiving at least 500 mL IV crystalloid within 48 hours of SIRS. Patient data was extracted from a large multi-hospital electronic health record database between January 1, 2009, and March 31, 2013. The primary outcome was in-hospital mortality. Secondary outcomes included length of stay, readmission, and complications measured by ICD-9 coding and clinical definitions. Outcomes were adjusted for illness severity using the Acute Physiology Score. Of the 91,069 patients meeting inclusion criteria, 89,363 (98%) received 0.9% saline whereas 1706 (2%) received a calcium-free balanced solution as the primary fluid. RESULTS: There were 3116 well-matched patients, 1558 in each cohort. In comparison with the calcium-free balanced cohort, the saline cohort experienced greater in-hospital mortality (3.27% vs. 1.03%, P <0.001), length of stay (4.87 vs. 4.38 days, P = 0.016), frequency of readmission at 60 (13.54 vs. 10.91, P = 0.025) and 90 days (16.56 vs. 12.58, P = 0.002) and frequency of cardiac, infectious, and coagulopathy complications (all P < 0.002). Outcomes were defined by administrative coding and clinically were internally consistent. Patients in the saline cohort received more chloride and had electrolyte abnormalities requiring replacement more frequently (P < 0.001). No differences were found in acute renal failure. CONCLUSIONS: In this large electronic health record, the predominant use of 0.9% saline in patients with SIRS was associated with significantly greater morbidity and mortality compared with predominant use of balanced fluids. The signal is consistent with that reported previously in perioperative and critical care patients. Given the large population of hospitalized patients receiving IV fluids, these differences may confer treatment implications and warrant corroboration via large clinical trials. TRIAL REGISTRATION: NCT02083198 clinicaltrials.gov; March 5, 2014. PMID- 26370824 TI - Erratum to: Association between osteocalcin and glucose metabolism: a meta analysis. PMID- 26370825 TI - Erratum to: Taxonomy of rare genetic metabolic bone disorders. PMID- 26370826 TI - 3D X-ray ultra-microscopy of bone tissue. AB - We review the current X-ray techniques with 3D imaging capability at the nano scale: transmission X-ray microscopy, ptychography and in-line phase nano tomography. We further review the different ultra-structural features that have so far been resolved: the lacuno-canalicular network, collagen orientation, nano scale mineralization and their use as basis for mechanical simulations. X-ray computed tomography at the micro-metric scale is increasingly considered as the reference technique in imaging of bone micro-structure. The trend has been to push towards increasingly higher resolution. Due to the difficulty of realizing optics in the hard X-ray regime, the magnification has mainly been due to the use of visible light optics and indirect detection of the X-rays, which limits the attainable resolution with respect to the wavelength of the visible light used in detection. Recent developments in X-ray optics and instrumentation have allowed to implement several types of methods that achieve imaging that is limited in resolution by the X-ray wavelength, thus enabling computed tomography at the nano scale. We review here the X-ray techniques with 3D imaging capability at the nano scale: transmission X-ray microscopy, ptychography and in-line phase nano tomography. Further, we review the different ultra-structural features that have so far been resolved and the applications that have been reported: imaging of the lacuno-canalicular network, direct analysis of collagen orientation, analysis of mineralization on the nano-scale and use of 3D images at the nano-scale to drive mechanical simulations. Finally, we discuss the issue of going beyond qualitative description to quantification of ultra-structural features. PMID- 26370827 TI - The long-term effect of comprehensive geriatric care on gait after hip fracture: the Trondheim Hip Fracture Trial--a randomised controlled trial. AB - SUMMARY: At present, most hip fracture patients are treated in orthopaedic wards. This study showed that a relatively short hospital intervention based on principles of comprehensive geriatric assessment resulted in safer and more efficient gait as long as 1 year following the fracture as compared to conventional orthopaedic treatment. INTRODUCTION: Hip fracture patients are frail, and the fracture is usually followed by substantial decline in gait function. Few studies have assessed gait characteristics other than gait speed and knowledge about the effect of early intervention on long-term gait outcome is sparse. The purpose of this study was to evaluate the long-term effect of pre- and post-surgery Comprehensive Geriatric Care (CGC) on ability to walk, self reported mobility and gait characteristics in hip fracture patients. METHODS: Two armed, parallel group randomised controlled trial comparing CGC to conventional Orthopaedic Care (OC) in pre- and early post-surgery phase. Hip fracture patients (n = 397), community-dwelling, age >70 years and able to walk at time of the fracture were included. Spatial and temporal gait characteristics were collected using an instrumented walkway (GAITRite(r) system) 4 and 12 months post-surgery. RESULTS: Participants who received CGC had significantly higher gait speed, less asymmetry, better gait control and more efficient gait patterns, more participants were able to walk and participants reported better mobility 4 and 12 months following the fracture as compared to participants receiving OC. CONCLUSIONS: Pre- and post-surgery CGC showed an effect on gait as long as 1 year after hip fracture. These findings underscore the importance of targeting the vulnerability of these patients at an early stage to prevent gait decline in the long run. As presently, most hip fracture patients are treated in orthopaedic wards with larger focus on the fracture than on frailty, these results are important to inform new models for hip fracture care. PMID- 26370828 TI - The use of bisphosphonate in the treatment of osteonecrosis of the femoral head: a meta-analysis of randomized control trials. AB - This meta-analysis revealed that bisphosphonates could not provide a better clinical outcome in the treatment of osteonecrosis of the femoral head (ONFH) when compared with placebo. INTRODUCTION: Bisphosphonates have been recommended to treat ONFH. However, the exact clinical outcomes after treatment are still controversial. METHODS: A comprehensive search of PubMed, Embase, and Web of Science databases was undertaken, and only randomized control trials were included. The clinical outcomes consisted of progression to collapse, total hip arthroplasty (THA) incidence, and improvement of Harris hip score (HHS). The heterogeneities between the trials were assessed with the I (2) statistic, and random effects models were used for the meta-analysis. RESULTS: Five eligible trials were identified involving 329 subjects with 920.9 patient-years of follow up. The clinical outcomes of patients with ONFH was not significantly improved by bisphosphonate therapy (progression to collapse: risk ratio = 0.71 (0.41, 1.24), p = 0.23; THA incidence: risk ratio = 0.61 (0.33, 1.15), p = 0.13; HHS improvement: mean difference = 3.26 (-5.12, 11.64), p = 0.45). The I (2) statistic showed the existence of considerable heterogeneity (all I (2) >= 50 %), which was explained by one trial where bisphosphonate alone was used with no additional therapy. However, when this trial was excluded, the clinical outcomes after bisphosphonate therapy were still not significantly improved compared with placebo. CONCLUSIONS: The current analysis does not support the use of bisphosphonates for ONFH. As potential serious adverse effects are associated with these drugs, only limited use can be recommended. PMID- 26370829 TI - High and anisotropic carrier mobility in experimentally possible Ti2CO2 (MXene) monolayers and nanoribbons. AB - MXene, a new kind of two-dimensional (2D) material, has a unique combination of excellent physical and chemical properties. Via computations on density functional theory and deformation potential theory, we investigated the electronic structure and predicted the carrier mobility of Ti2CO2 (a typical MXene) monolayers and nanoribbons. The Ti2CO2 monolayer is a semiconductor with a band gap of 0.91 eV, and the hole mobility in the monolayer reaches 10(4) orders of magnitude along both x and y directions, which is much higher than that of MoS2, while the electron mobility is about two orders of magnitude lower. The dramatic difference between the hole and electron mobilities also exists in nanoribbons. Moreover, our results suggest that width controlling and edge engineering would be effective in adjusting the carrier mobility of Ti2CO2 nanoribbons, and endow experimentally available Ti2CO2 with wide applications to field-effect transistors and photocatalysts. PMID- 26370830 TI - The role of hereditary KCNQ1 mutations in water-related death. AB - Drowning remains one of the major causes of death in most developed countries despite the fact that many of the victims are known to be at least moderate swimmers as well as healthy directly before the event. Here, fatal arrhythmias and especially the long QT syndrome (LQTS) have been proposed as the underlying mechanism which may be connected to mutations in one of the associated genes. The KCNQ1 gene is involved in the occurrence of LQT1 which may be triggered by swimming. Therefore, 176 cases of drowning were screened for mutations in the exons 3, 5, 6, 7, and 8 of the KCNQ1 gene which have been shown to harbor major mutation clusters. No variation to the published sequence could be found in the exonic DNA in any of the cases clearly disproving an involvement of these mutation clusters in cases of drowning. PMID- 26370831 TI - Perceived Benefits of Implantable Cardioverter Defibrillator Implantation among Heart Failure Patients and Its Relation to Quality of Life: A Cross-Sectional Study. AB - INTRODUCTION: Patients with heart failure (HF) and implantable cardioverter defibrillators (ICDs) may misunderstand the indication of ICDs due to unsatisfactory information. The goal of this study is to evaluate the patient perspective of ICD indication and its relation to quality of life, as well as to identify probable communication gaps between doctors and ICD receivers. METHODS: A total of 119 patients with HF who were implanted with a single-chamber ICD were evaluated in outpatient clinics. Patients with cardiac resynchronization therapy defibrillators were not included in the study. In a questionnaire, patients were asked about the indication of the ICD procedure and classified according to the perceived benefits. RESULTS: This study showed that most of the patients (n = 92, 77.3%) believed that ICD was implanted for improvement of heart dysfunction or for symptom relief. According to the perceived benefit groups, physical function, general health, vitality, and role physical scores were significantly lower in the symptom relief group (p < 0.05). CONCLUSION: Patients with HF and ICD mostly believed that the cardioverter defibrillator implanted for improving heart function or symptom relief. Doctors play a significant role when a patient is first referred for ICD because less-informed patients are more prone to misunderstand the procedure's benefits. Moreover, unfulfilled expectations may lead to loss of confidence in applied therapies and result in poor health outcomes. PMID- 26370832 TI - Oncogenic Drivers in Myeloproliferative Neoplasms: From JAK2 to Calreticulin Mutations. AB - During the past 10 years, major progress has been accomplished with the discovery of activating mutations that are associated with the vast majority of BCR-ABL negative human myeloproliferative neoplasms (MPNs). The identification in 2005 of JAK2 V617F triggered great interest in the JAK2-STAT5/STAT3 pathway. Discovery in 2006 of mutants of thrombopoietin receptor (TPO-R/MPL) and later on of mutants in negative regulators of JAK-STAT pathway led to the notion that persistent JAK2 activation is a hallmark of MPNs. In 2013, mutations in the gene coding for the chaperone calreticulin were reported in 20-30% of essential thrombocythemia and primary myelofibrosis patients. Here, we will address the question: what do we know about calreticulin that could help us understand its role in MPNs? In addition to oncogenic driver mutations, certain MPNs also exhibit epigenetic mutations. Targeting of both oncogenic drivers and epigenetic defects could be required for effective therapy. PMID- 26370833 TI - Translation, cross-cultural adaptation and psychometric evaluation of yoruba version of the short-form 36 health survey. AB - BACKGROUND AND OBJECTIVE: The Short-Form Health Survey (SF-36) is a valid quality of life tool often employed to determine the impact of medical intervention and the outcome of health care services. However, the SF-36 is culturally sensitive which necessitates its adaptation and translation into different languages. This study was conducted to cross-culturally adapt the SF-36 into Yoruba language and determine its reliability and validity. METHODS: Based on the International Quality of Life Assessment project guidelines, a sequence of translation, test of item-scale correlation, and validation was implemented for the translation of the Yoruba version of the SF-36. Following pilot testing, the English and the Yoruba versions of the SF-36 were administered to a random sample of 1087 apparently healthy individuals to test validity and 249 respondents completed the Yoruba SF 36 again after two weeks to test reliability. Data was analyzed using Pearson's product moment correlation analysis, independent t-test, one-way analysis of variance, multi trait scaling analysis and Intra-Class Correlation (ICC) at p < 0.05. RESULTS: The concurrent validity scores for scales and domains ranges between 0.749 and 0.902 with the highest and lowest scores in the General Health (0.902) and Bodily Pain (0.749) scale. Scale-level descriptive result showed that all scale and domain scores had negative skewness ranging from -2.08 to -0.98. The mean scores for each scales ranges between 83.2 and 88.8. The domain scores for Physical Health Component and Mental Health Component were 85.6 +/- 13.7 and 85.9 +/- 15.4 respectively. The convergent validity was satisfactory, ranging from 0.421 to 0.907. Discriminant validity was also satisfactory except for item '1'. The ICC for the test-retest reliability of the Yoruba SF-36 ranges between 0.636 and 0.843 for scales; and 0.783 and 0.851 for domains. CONCLUSION: The data quality, concurrent and discriminant validity, reliability and internal consistency of the Yoruba version of the SF-36 are adequate and it is recommended for measuring health-related quality of life among Yoruba population. PMID- 26370834 TI - Ameliorating effects of gypenosides on chronic stress-induced anxiety disorders in mice. AB - BACKGROUND: Ethanol extract from Gynostemma pentaphyllum (GP) shows anti-stress and anxiolytic functions in mice, and also protects dopamine neurons in 6 hydroxydopamine-lesioned rat model of Parkinson's disease. In addition, gypenosides (the gypenoside-enriched components of GP, GPS) have a protective effect on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease. In this study, the ameliorating effects of GPS on chronic stress-induced anxiety disorders in mice were investigated. METHODS: Mice were orally treated with GPS (100 and 200 mg/kg) once a day for 10 days, followed by exposure to electric footshock (EF) stress (0.6 mA, 1 s every 5 s, 3 min). After the final administration of either GPS, water extract of GP (GP-WX) or ethanol extract of GP (GP-EX, positive control), the behavioral tests such as elevated plus-maze, marble burying and locomotor activity tests, and the biochemical parameters including dopamine, serotonin and corticosterone levels, and c-Fos expression were examined. RESULTS: Treatment with GPS (100 and 200 mg/kg) increased the number of open arm entries and the time spent on open arms in elevated plus-maze which were reduced by chronic EF stress. GPS (100 and 200 mg/kg) reduced the number of marbles buried which increased by chronic EF stress. In these states, the brain levels of dopamine and serotonin decreased by chronic EF stress and they were recovered by GPS. The serum levels of corticosterone increased by chronic EF stress were also reduced by GPS (100 and 200 mg/kg). Finally, chronic EF stress-induced c-Fos expression was markedly reduced by GPS (100 and 200 mg/kg) in the brain. GPS (100 and 200 mg/kg) also showed an equivalent efficacy on anxiolytic functions, as compared with GP-EX (50 mg/kg). However, GP-WX (50 mg/kg) showed a less effect on anxiety disorders than GP-EX (50 mg/kg) and GPS (100 and 200 mg/kg). CONCLUSION: These results suggest that GPS (100 and 200 mg/kg) has anxiolytic effects on chronic EF stress-induced anxiety disorders by modulating dopamine and serotonin neuronal activities, c-Fos expression and corticosterone levels. GPS may serve as a phytonutrient in chronic stress-induced anxiety disorders. PMID- 26370835 TI - A statistical method for assessing network stability using the Chow test. AB - A statistical method is proposed for the assessment of stability in noise monitoring networks. The technique makes use of a variation of the Chow test applied between multiple measurement nodes placed at different locations and its novelty lies in the way it utilises a simple statistical test based on linear regression to uncover complex issues that can be difficult to expose otherwise. Measurements collected by a noise monitoring network deployed in the center of Pisa are used to demonstrate the capabilities and limitations of the test. It is shown that even in urban environments, where great soundscape variations are exhibited, accurate and robust results can be produced regardless of the proximity of the compared sensors as long as they are located in acoustically similar environments. Also it is shown that variations of the same method can be applied for self-testing on data collected by single stations. Finally it is presented that the versatility of the test makes it suitable for detection of various types of issues that can occur in real life network implementations; from slow drifts away from calibration, to severe, abrupt failures and noise floor shifts. PMID- 26370836 TI - Experimental analysis of the six-channel cyclone with spiral shell. AB - Experimental analysis is conducted in order to estimate the distribution of air (gas) flow velocity in the advanced six-channel cyclone with spiral shell, and to measure the resistance and purifying effectiveness of the cyclone with spiral shell. The device is used for separating the minuscule solid particles from contaminated air (gas) flow. The multifunctional measuring instrument TESTO-452 with the attached Pito-Prandtl tube was used for carrying out the experiments. The air (gas) velocity in all six-cyclone channels, the resistance of six-channel cyclone with spiral shell and the effectiveness of air (gas) flow purification, depending on the position of curvilinear semi-rings and the average air (gas) flow velocity in the cyclone channels, were measured during the experiments. PMID- 26370837 TI - Genome-wide association study in Chinese Holstein cows reveal two candidate genes for somatic cell score as an indicator for mastitis susceptibility. AB - BACKGROUNDS: Bovine mastitis is a typical inflammatory disease causing seriously economic loss. Genome-wide association study (GWAS) can be a powerful method to promote marker assistant selection of this kind of complex disease. The present study aimed to analyze and identify single nucleotide polymorphisms (SNPs) and candidate genes that associated with mastitis susceptibility traits in Chinese Holstein. RESULTS: Forty eight SNPs were identified significantly associated with mastitis resistance traits in Chinese Holstein cows, which are mainly located on the BTA 14. A total of 41 significant SNPs were linked to 31 annotated bovine genes. Gene Ontology and pathway enrichment revealed 5 genes involved in 32 pathways, in which, TRAPPC9 and ARHGAP39 genes participate cell differentiation and developmental pathway together. The six common genome-wide significant SNPs are found located within TRAPPC9 and flanking ARHGAP39 genes. CONCLUSIONS: Our data identified the six SNPs significantly associated with SCS EBVs, which suggest that their linked two genes (TRAPPC9 and ARHGAP39) are novel candidate genes of mastitis susceptibility in Holsteins. PMID- 26370840 TI - In this issue of Occupational Medicine. PMID- 26370838 TI - Targeting B-cell maturation antigen in multiple myeloma. AB - Novel effective immunotherapies are needed for patients with multiple myeloma (MM), since disease recurrence remains a major obstacle. B-cell maturation antigen (BCMA), a cell surface protein universally expressed on malignant plasma cells , has emerged as a very selective antigen to be targeted in novel treatments for MM. We here first review BCMA-related biology, and then highlight the recent clinical development of a novel afucosylated anti-BCMA monoclonal antibody conjugated with monomethyl auristatin F via noncleavable linker (GSK2857916). Chimeric antigen receptor-expressing T cells targeting BCMA may also induce specific and durable anti-MM responses by patients' own effector cells. Clinical trials testing these two approaches (NCT02064387, NCT02215967) are currently ongoing in relapsed and refractory MM patients. PMID- 26370841 TI - Illness deception. PMID- 26370839 TI - Apremilast, a novel phosphodiesterase 4 (PDE4) inhibitor, regulates inflammation through multiple cAMP downstream effectors. AB - INTRODUCTION: This work was undertaken to delineate intracellular signaling pathways for the PDE4 inhibitor apremilast and to examine interactions between apremilast, methotrexate and adenosine A2A receptors (A2AR). METHODS: After apremilast and LPS incubation, intracellular cAMP, TNF-alpha, IL-10, IL-6 and IL 1alpha were measured in the Raw264.7 monocytic murine cell line. PKA, Epac1/2 (signaling intermediates for cAMP) and A2AR knockdowns were performed by shRNA transfection and interactions with A2AR and A2BR, as well as with methotrexate were tested in vitro and in the murine air pouch model. Statistical differences were determined using one or two-way ANOVA or Student's t test. The alpha nominal level was set at 0.05 in all cases. A P value of < 0.05 was considered significant. RESULTS: In vitro, apremilast increased intracellular cAMP and inhibited TNF-alpha release (IC50=104nM) and the specific A2AR-agonist CGS21680 (1MUM) increased apremilast potency (IC50=25nM). In this cell line, apremilast increased IL-10 production. PKA, Epac1 and Epac2 knockdowns prevented TNF-alpha inhibition and IL-10 stimulation by apremilast. In the murine air pouch model, both apremilast and MTX significantly inhibited leukocyte infiltration, while apremilast, but not MTX, significantly inhibited TNF-alpha release. The addition of MTX (1 mg/kg) to apremilast (5 mg/kg) yielded no more inhibition of leukocyte infiltration or TNF-alpha release than with apremilast alone. CONCLUSIONS: The immunoregulatory effects of apremilast appear to be mediated by cAMP through the downstream effectors PKA, Epac1, and Epac2. A2AR agonism potentiated TNF-alpha inhibition by apremilast, consistent with the cAMP-elevating effects of that receptor. Because the A2AR is also involved in the anti-inflammatory effects of MTX, the mechanism of action of both drugs involves cAMP-dependent pathways and is therefore partially overlapping in nature. PMID- 26370842 TI - Occupational histories. PMID- 26370843 TI - Rudolf Fyodorovich Vilde, Victory for the Workers 1921. PMID- 26370844 TI - Fifty years ago: 'Laser hazards'. PMID- 26370845 TI - Hamilton Rating Scale for Anxiety (HAM-A). PMID- 26370846 TI - Molecular basis of death effector domain chain assembly and its role in caspase-8 activation. AB - Assembly of a death-inducing signaling complex is a key event in the extrinsic apoptotic pathway, enabling activation of the caspase cascade and subsequent cell death. However, the molecular events governing DISC assembly have remained largely elusive because of the lack of information on mechanism and specificity regulating the death effector domain (DED)-DED interaction network. Using molecular modeling, mutagenesis, and biochemical and ex vivo experiments, we identified the precise binding interface and hot spots crucial for intermolecular DED chain assembly. Mutation of key interface residues (Leu42/Phe45) in procaspase-8 DED-A completely abrogated DED chain formation in HEK293 cells and prevented its association with FADD. A significant 2.6-3.6-fold reduction in procaspase-8 activation was observed in functional cell-death assays after substitution of the interfacial residues. Based on our results we propose a new model for DISC formation that refines the current understanding of the activation mechanism. Upon stimulation, FADD self-associates weakly via reciprocal interaction between helices alpha1/alpha4 and alpha2/alpha3 of the DED to form an oligomeric signaling platform that provides a stage for the initial recruitment of procaspase-8 through direct interaction with alpha1/alpha4 of DED-A, followed by sequential interaction mediated by helices alpha2/alpha5 of DED-B, to form the procaspase-8 DED chain that is crucial for its activation and subsequent cell death. PMID- 26370847 TI - The microbiota shifts the iron sensing of intestinal cells. AB - The amount of iron in the diet directly influences the composition of the microbiota. Inversely, the effects of the microbiota on iron homeostasis have been little studied. So, we investigate whether the microbiota itself may alter host iron sensing. Duodenal cytochrome b and divalent metal transporter 1, involved in apical iron uptake, are 8- and 10-fold, respectively, more abundant in the duodenum of germ-free (GF) mice than in mice colonized with a microbiota. In contrast, the luminal exporter ferroportin is 2-fold less abundant in GF. The overall signature of microbiota on iron-related proteins is similar in the colon. The colonization does not modify systemic parameters as plasma transferrin saturation (20%), plasma ferritin (150 ng/L), and liver (85 ug/g) iron load. Commensal organisms (Bacteroides thetaiotaomicron VPI-5482 and Faecalibacterium prausnitzii A2-165) and a probiotic strain (Streptococcus thermophilus LMD-9) led to up to 12-fold induction of ferritin in colon. Our data suggest that the intestinal cells of GF mice are depleted of iron and that following colonization, the epithelial cells favor iron storage. This study is the first to demonstrate that gut microbes induce a specific iron-related protein signature, highlighting new aspects of the crosstalk between the microbiota and the intestinal epithelium. PMID- 26370849 TI - Saliva as an alternative specimen for detection of Schmallenberg virus-specific antibodies in bovines. AB - BACKGROUND: Schmallenberg virus (SBV), discovered in continental Europe in late 2011, causes mild clinical signs in adult ruminants, including diarrhoea and reduced milk yield. However, fetal infection can lead to severe malformation in newborn offspring. Enzyme-linked immunosorbent assays (ELISA) are commercially available for detection of SBV-specific antibodies in bovine sera and milk. Here we describe the development and evaluation of an indirect ELISA based on a yeast derived recombinant SBV nucleocapsid protein (N) for the detection of SBV specific antibodies in bovine saliva. Development of a non-invasive test to detect antibodies in individual bovine saliva samples could potentially provide a test suitable for calves and adult cattle. The aim of this study was to investigate the agreement between the levels of antibodies (IgG) measured in milk and sera, and the level of antibodies (IgG and IgA) in saliva, in comparison with the antibody levels detected in sera and milk with commercially available test. RESULTS: Serum, milk and saliva samples from 58 cows were collected from three dairy herds in Lithuania and tested for the presence of SBV-specific antibodies. The presence of IgG antibodies was tested in parallel serum and milk samples, while the presence of IgA and IgG antibodies was tested in saliva samples. The presence of SBV-specific IgG and IgA in saliva was tested using an indirect ELISA based on a yeast-derived recombinant N protein. The presence of SBV-specific IgG in milk and sera was tested in parallel using a commercial recombinant protein based test. The sensitivities of the newly developed tests were as follows: 96 % for the IgG serum assay and 94 % for the IgG milk assay and 85 % and 98 % for IgG and IgA in saliva tests, when compared with data generated by a commercial IgG assay. CONCLUSIONS: Data from testing the saliva IgG and IgA and also the milk and serum IgG with indirect SBV-specific ELISAs showed close agreement with the commercial serum and milk IgG assay data. The level of IgG in saliva was notably lower in comparison to IgA. The newly developed method exhibits the potential to serve as an easily transferable tool for epidemiological studies. PMID- 26370850 TI - Blood Pressure Management in Patients with Type 2 Diabetes. AB - In patients with type 2 diabetes (T2DM), the coexistence of hypertension enhances the cardiovascular risk, and the prevention of future cardiovascular disease is an important component of T2DM management. Antihypertensive therapy has been shown to be an effective method of reducing the micro- and macrovascular complications of T2DM, however, the optimal target blood pressure (BP) levels are still under debate. Most of the international guidelines have raised the target clinic BP from 130/80 to 140/90 mmHg, however, the Japanese Society of Hypertension 2014 guidelines kept the target BP level at 130/80 mmHg. However, individualized BP-lowering treatments should be considered in patients with T2DM, especially in high-risk individuals such as those with a history of stroke or retinopathy, and aggressive antihypertensive therapy below 130 mmHg should be initiated even when the initial systolic BP level is <140 mmHg. The authors performed two studies concerning the BP target levels of home BP. In the first study, the authors found that a home BP target <125/75 mmHg was effective in improving the measures of vascular stiffness and kidney damage. In the second study, when the clinic BP target was set at 130/80 mmHg, the home BP could be approximately 130/80 mmHg. More data are needed to individualize the target BP levels of T2DM patients. PMID- 26370848 TI - Molecular mechanisms for mitochondrial adaptation to exercise training in skeletal muscle. AB - Exercise training enhances physical performance and confers health benefits, largely through adaptations in skeletal muscle. Mitochondrial adaptation, encompassing coordinated improvements in quantity (content) and quality (structure and function), is increasingly recognized as a key factor in the beneficial outcomes of exercise training. Exercise training has long been known to promote mitochondrial biogenesis, but recent work has demonstrated that it has a profound impact on mitochondrial dynamics (fusion and fission) and clearance (mitophagy), as well. In this review, we discuss the various mechanisms through which exercise training promotes mitochondrial quantity and quality in skeletal muscle. PMID- 26370851 TI - Validation of the Estimation of Low-density Lipoprotein Cholesterol by the Modified Friedewald Equation in Ethnic Chinese Adults Living in Taiwan. AB - OBJECTIVE: The Friedewald equation has been used as the standard formula for the estimation of very low-density lipoprotein cholesterol (VLDL-C) to calculate the serum levels of low-density lipoprotein cholesterol (LDL-C). However, the usefulness of this formula in non-Caucasians has been challenged in recent years. The aim of this study was to assess the validity of the conventional and modified Friedewald equation in an ethnic Chinese adult population. METHODS: We prospectively recruited 938 subjects from the Lipid Clinic of the National Taiwan University Hospital. The fasting lipids, including cholesterol, high-density lipoprotein cholesterol, LDL-C, VLDL-C, and triglycerides (TGs), of each participant were measured and we constructed a prediction model for the estimation of LDL-C by the modified Friedewald equation. RESULTS: The constant values, used to estimate the VLDL-C concentration, were different in the Friedewald equation in the subgroups exhibiting different cardiovascular characteristics, ranging from 4.45 to 6.63, if we calculated the equation by a direct LDL-C measurement. According to the results of a stepwise multiple linear regression analysis excluding the TG levels >=400 mg/dL, an equation for the individual constant Y estimation was as follows: Constant Y = 4.39 + (-0.59) if the age >=50 years + 0.98 if men + TG group (2.06 if the TG levels were between 150-399 mg/dL; 1.07 if the TG levels were between 100-149 mg/dL) + (-0.49) if the cholesterol levels >=240 mg/dL + the body mass index (BMI) group (0.8 if BMI >=27 kg/m(2); 0.48 if BMI =24-27 kg/m(2)). CONCLUSION: This modified Friedewald formula provides a new and simple equation for calculating the LDL-C levels in ethnic Chinese people. PMID- 26370852 TI - Myocardial Injury after Percutaneous Coronary Intervention for In-Stent Restenosis Versus de novo Stenosis. AB - OBJECTIVE: Periprocedural myocardial injury (PMI) remains a relatively common complication even after successful procedures. In-stent restenosis (ISR) may be involved in lesion-related factors for PMI. We compared the incidence of PMI between patients with ISR and those with de novo stenosis. METHODS: The study population consisted of 121 patients with coronary artery disease who had been treated with statins and subsequently underwent angiographically successful percutaneous coronary intervention (PCI). Blood samples for troponin I were collected 18 to 24 hours after PCI. PMI was defined as an increase in the troponin I levels greater than 0.15 ng/mL. Major PMI was defined as an increase in the troponin I levels greater than 0.75 ng/mL. RESULTS: There were 34 patients with ISR and 87 patients with de novo stenosis. The incidence of PMI was similar between the two groups (47.1 % vs. 55.2 %, p=0.42). Among the patients with ISR, the incidences of PMI were 33.3 %, 60.0 % and 66.7 % in patients with focal ISR, diffuse ISR and diffuse proliferative ISR, respectively, although these differences were not statistically significant. The incidence of major PMI was significantly less frequent in patients with ISR than those with de novo stenosis (5.9 % vs. 25.3 %, p=0.03). A multivariate logistic regression analysis showed that ISR [odds ratio (OR) 0.22, 95% confidence interval (CI) 0.03-0.90; p=0.03] and the maximum inflation pressure (OR 1.15, 95% CI 1.04-1.30; p=0.009) were independent predictors of major PMI. CONCLUSION: Our results suggest that while PMI occurs in patients with ISR as commonly as those with de novo stenosis, major PMI occurs less frequently in patients with ISR. PMID- 26370853 TI - High-Flow Nasal Cannula Therapy for Acute Hypoxemic Respiratory Failure in Adults: A Retrospective Analysis. AB - OBJECTIVE: High-flow nasal cannula (HFNC) therapy is an oxygen delivery system. However, evidence regarding the clinical applications of HFNC is still emerging. We herein evaluated the clinical predictors of HFNC therapy success for adult patients with acute hypoxemic respiratory failure. METHODS: We retrospectively reviewed the medical records of the subjects with acute hypoxemic respiratory failure supported by HFNC therapy in the medical intensive care unit between July 2011 and March 2013. Therapy success was defined as the avoidance of intubation. The patients' baseline characteristics and the serial changes in the respiratory parameters after HFNC therapy at 1 and 24 hours were measured. RESULTS: Of the 75 eligible patients, 62.7% successfully avoided intubation. Overall, HFNC therapy significantly improved the physiologic parameters, such as partial pressure of arterial oxygen (PaO2), saturation of arterial oxygen (SaO2), respiratory rate (RR), and heart rate (HR), throughout the first 24 hours. After the adjustment for the other clinical variables, Acute Physiology and Chronic Health Evaluation II (APACHE II), Sequential Organ Failure Assessment (SOFA), cardiogenic pulmonary edema, and PaO2 improvement at 1 and 24 hours were associated with therapy success. The overall intensive care unit (ICU) mortality was 25.3%. However, out of 37.3% of the patients who required intubation, the ICU mortality in this proportion of patients was 67.9%. The ICU mortality in the therapy failure group was associated with the use of a vasopressor and a limited PaO2 improvement at 1 hour. CONCLUSION: HFNC therapy showed a good compliance and the improvement of the physiologic parameters in an adult population. The failure to improve oxygenation within 24 hours was a useful predictor of intubation. Among the failure group, the vasopressor use and failed oxygenation improvement were associated with ICU mortality. PMID- 26370854 TI - Currently Used Low-Dose Pyrazinamide Does Not Increase Liver-Injury in the First Two Months of Tuberculosis Treatment. AB - OBJECTIVE: In the 1950s, a high-dose (40-70 mg/kg/day) of pyrazinamide (PZA), was reported to cause drug-induced liver injury (DILI) at an unacceptable frequency. It remains unclear whether adding PZA (Z) at the currently accepted low-dose (20 25 mg/kg/day) for two months to a regimen of isoniazid (H) + rifampicin (R) + ethambutol (E) actually increases the risk of DILI. METHOD: Smear-positive tuberculosis patients were treated with daily HRE or HRZE regimen under direct observation. We used three independent models. Model 1 was analyzed with a multivariate Cox-analysis using a pre-matched cohort. Next, propensity score matching was conducted using the nearest neighbor method with caliper of 0.03. Models 2 and 3 were analyzed by univariate and multivariate Cox-analyses, respectively, with the matched cohort. DILI was assessed based on the guidelines of the American Thoracic Society. RESULTS: We reviewed the records of 383 patents (male, n=260; female n=123; mean age, 64+/-20 years). Among these patients, 75 patients were treated with HRE and 308 were treated with HRZE. DILI occurred in the first two months in 24% (18/75) and 8% (24/308) of the HRE-treated and HRZE treated cases, respectively. In all three of the models, DILI was less frequent in patients treated with the HRZE regimen: Model 1, HR of 0.30 (95% confidence interval (CI) 0.14-0.68, p=0.004); Model 2, HR of 0.37 (95%CI 0.14-0.96, p=0.041); and Model 3, HR of 0.34 (95%CI 0.12-0.94, p=0.038). CONCLUSION: The addition of the currently accepted low dose (20-25 mg/kg/day) of PZA to the HRE regimen did not increase the incidence of DILI during the first two months of treatment. PMID- 26370855 TI - Photodynamic Therapy using Talaporfin Sodium for the Recurrence of Cholangiocarcinoma after Surgical Resection. AB - We herein report the case of a 72-year-old man who underwent photodynamic therapy (PDT) with talaporfin sodium for recurrent cholangiocarcinoma after surgical resection. Endoscopic retrograde cholangiography (ERC) showed severe stenosis with an irregular surface measuring approximately 1 cm in length from the anastomotic site, and a recurrent nodular lesion was observed at the anastomotic site of the right anterior intrahepatic bile duct on gastrointestinal endoscopy. ERC after PDT revealed a dramatic improvement in the bile duct stenosis, and the nodular lesion had disappeared. No adverse events from the PDT were detected. PDT using talaporfin sodium may be a safe alternative treatment for cholangiocarcinoma. PMID- 26370856 TI - Hypothyroidism Enhanced Portal Hypertension in a Patient with Alcoholic Liver Cirrhosis, Resulting in the Development of Ascites. AB - A man diagnosed with alcoholic liver cirrhosis complained of abdominal distention due to massive ascites. The ascites did not resolve with diuretic agents. The serum-ascites albumin gradient value of 1.9 g/dL and the total protein level in the ascites of 3.1 g/dL indicated the ascites to have been caused by portal hypertension. Hypothyroidism was detected, and the patient received supplementation with levothyroxine. The ascites dramatically decreased after supplementation with levothyroxine. We herein conclude that the ascites in the present case had thus been strongly influenced by portal hypertension, which was induced by liver dysfunction associated with liver cirrhosis and hypothyroidism. PMID- 26370857 TI - Two Case Reports of Group B Streptococcal Infective Endocarditis Complicated by Embolism. AB - Streptococcus agalactiae (Group B streptococcus, GBS) is the major pathogen encountered in the perinatal period, although the incidence of GBS infection has recently increased among non-pregnant adults. Nevertheless, GBS infective endocarditis (IE) is uncommon and often accompanies aortic embolism. We experienced two cases of GBS IE. In Case 1, mobile vegetation of the aortic valve caused an infective cerebral aneurysm. In Case 2, the patient experienced an acute aortic embolic episode. Generally, early surgery for large mobile sites of vegetation is recommended as a class IIb therapy in the guidelines. GBS IE often exhibits a severe clinical course and specificity of vegetation. Therefore, early surgery should be considered in such cases. PMID- 26370858 TI - Elevated Serum IgG4 Complicated by Pericardial Involvement with a Patchy (18)F FDG Uptake in PET/CT: Atypical Presentation of IgG4-related Disease. AB - IgG4-related pericardial involvement has rarely been reported and its clinical features remain unknown. We herein report a case of a 50-year-old woman with pericarditis who presented with a fever, elevated C-reactive protein levels, elevated serum IgG4 concentrations, and thickened pericardium with a patchy (18)F fluorodeoxyglucose (FDG) uptake. A biopsy specimen of (18)F-FDG accumulated in the mediastinal lymph nodes revealed an abundant infiltration of IgG4-bearing plasma cells without fibrosis. Moderate-dose glucocorticoids promptly resolved the physical, serological, and imaging abnormalities, thus indicating a relatively acute and reversible nature of IgG4-related pericardial involvement. PMID- 26370859 TI - Ventricular Rhythm and Hypotension in a Patient with Pheochromocytoma-induced Myocardial Damage and Reverse Takotsubo Cardiomyopathy. AB - A 33-year-old woman experienced near-syncope at a hospital. Electrocardiography revealed an intermittent ventricular rhythm. The echocardiogram at admission indicated mild hypokinesis and severe diffuse hypokinesis with reverse takotsubo cardiomyopathy on the following day. The patient experienced abdominal pain on the admission day, and computed tomography identified a large left adrenal mass. Her catecholamine levels increased remarkably on the third day. The wall motion improved on the twelfth day. The tumor was successfully resected and the patient was diagnosed with an ectopic pheochromocytoma. The ventricular rhythm with myocardial damage and hypotension induced by the reverse takotsubo cardiomyopathy masked the characteristic symptoms of pheochromocytoma. PMID- 26370860 TI - Ischemic Cardiomyopathy with a Rapid Progression from Thrombotic Thrombocytopenic Purpura. AB - An 83-year-old woman who complained of dizziness and nausea visited our hospital. An electrocardiogram showed ST-segment elevation in multiple leads and an echocardiogram showed severe hypokinesis of the anteroseptal wall of the left ventricle. However, emergency coronary angiography showed no stenotic lesions in any coronary arteries. A laboratory examination showed thrombocytopenia, renal dysfunction, and hemolysis. We therefore diagnosed the patient with thrombotic thrombocytopenic purpura (TTP). While we were preparing to initiate plasma exchange therapy, she suddenly developed cardiopulmonary arrest. A postmortem examination revealed microthrombi in the small vessels of the myocardium. We herein report a case of ischemic cardiomyopathy with a rapid progression from TTP. PMID- 26370861 TI - A Patient with an Extra-adrenal Pheochromocytoma and Germ-line SDHB Mutation Accompanied by an Atypical Meningioma. AB - The gene succinate dehydrogenase subunit B (SDHB) encodes a protein comprising part of the mitochondrial complex II, which links the Krebs cycle and the electron-transport chain. Heterozygous germ-line SDHB mutations causes familial pheochromocytoma-paraganglioma syndrome and has also been linked to gastrointestinal stromal tumors, as well as renal cell carcinomas. We herein report a patient with a germ-line SDHB mutation who presented with an atypical meningioma that was identified as originating from a somatic SDHB mutation. The 41-year-old man, who had a surgical history of extra-adrenal pheochromocytoma at 23 years of age, recently developed gait disorder and hypertension. At the radiological examination, a tumor was detected in the cervical spinal cord at the C6-7 intervertebral level. The pathological findings of the isolated tumor were atypical meningioma assessed as grade II according to the World Health Organization criteria. Inherited neoplasia syndrome was suspected because of the patient's history of early-onset extra-adrenal pheochromocytoma and the development of meningioma. We therefore performed molecular genetic analyses. A direct sequence analysis revealed a heterozygous germ-line frameshift mutation in SDHB, specifically an 11-nucleotide deletion, c.305-315delCAATGAACATC, in exon 4, resulting in a frameshift p.A102EfsX12. Additionally, the sequence analysis of the tumor DNA revealed only a mutated allele with a frameshift mutation in the germ-line SDHB. Our findings suggest that SDHB plays an important role in the pathogenesis of meningiomas as well as pheochromocytomas. Therefore, a differential diagnosis for metastatic pheochromocytoma and other new onset tumors, including meningioma, particularly in patients with germ-line SDHB mutations and a previous history of pheochromocytoma should be carefully made. PMID- 26370862 TI - Type 1 Diabetes Mellitus and Pernicious Anemia in an Elderly Japanese Patient: A Case Report and Literature Review. AB - We herein report the case of a 66-year-old Japanese man with acute-onset type 1 diabetes mellitus (T1D) accompanied by pernicious anemia. After 2 weeks of polyuria, the patient developed insulin-deficient hyperglycemia with diabetic ketoacidosis in the absence of verifiable islet-related autoantibodies and began insulin therapy in 2001. Eight years later, he developed gastric autoantibody positive pernicious anemia and began methylcobalamin treatment. Previous studies have reported cases of slowly progressive autoimmune T1D concomitant with pernicious anemia. The present case suggests that potential associations with organ-specific autoimmune disorders should be considered during the long-term follow-up of T1D patients, even though verifiable islet-related autoantibodies are undetectable. PMID- 26370863 TI - Severe Insulin-resistant Diabetes due to Insulin Antibodies Associated with Eosinophilia. AB - A 66-year-old man with type 2 diabetes on hemodialysis treatment was admitted due to poor glycemic control. His serum insulin level and the (125)I-insulin binding rate were extremely high with an increased eosinophil count, although he did not have an allergic reaction to insulin or an elevation of specific IgE for human insulin. A Scatchard analysis revealed that the patient's insulin antibodies had a low affinity constant and a high binding capacity. Prednisolone administration decreased the eosinophil count and (125)I-insulin binding rate; accordingly, the glycemic control improved. Corticosteroid therapy may be a potent therapeutic strategy for insulin antibody-induced severe insulin resistance with eosinophilia. PMID- 26370864 TI - Minimal Change Nephrotic Syndrome Which Was Most Likely Caused by Chronic Sinusitis. AB - A 33-year-old Japanese man was admitted with severe edema, and a renal biopsy confirmed minimal change nephrotic syndrome (MCNS). CT revealed his severe chronic sinusitis, and he first received antimicrobial therapy, which resulted in decreased proteinuria. The surgical operation for sinusitis resulted in the complete disappearance of proteinuria without corticosteroid or immunosuppressant therapy within one week. MCNS may be triggered by infection, but there are no previously reported cases of MCNS that is completely remitted by infection control alone. Therefore, we herein report the first case of MCNS that attained complete remission following therapy for chronic sinusitis alone, which suggests a strong etiology of chronic sinusitis for MCNS. PMID- 26370865 TI - Aspirin and Eicosapentaenoic Acid May Arrest Progressive IgA Nephropathy: A Potential Alternative to Immunosuppression. AB - Immunoglobulin (Ig) A nephropathy is a prevalent form of primary glomerulonephritis, which leads to end-stage renal failure in a significant proportion of patients. Immunotherapy, including steroid use, is widely used to induce disease remission; however, it can cause serious side effects. We herein report 3 cases of progressive IgA nephropathy and their successful treatment with a combination of aspirin and eicosapentaenoic acid (EPA) without the use of steroids. The precise mechanism responsible for the combination therapy is still unknown; however, aspirin may potentiate the production of anti-inflammatory lipid mediators derived from EPA. Further clinical trials are required to substantiate this treatment regimen. PMID- 26370866 TI - Autoimmune Hemorrhaphilia Resulting from Autoantibody against the A Subunit of Factor XIII. AB - A 65-year-old woman was admitted with acute intramuscular hemorrhage of the left gluteus medius and piriformis muscles and associated anemia. Blood tests showed low plasma factor XIII (FXIII) antigen and activity. A cross-mixing test revealed a concave "inhibitor" pattern and anti-FXIII-A subunit antibody was detected. The patient was diagnosed with autoimmune hemorrhaphilia resulting from anti-FXIII antibody. The bleeding has not recurred since the initiation of treatment with oral immunosuppressive agents. Although hemorrhagic acquired FXIII deficiency is a rare disorder, prompt recognition of the underlying mechanism can save lives. PMID- 26370867 TI - A Japanese Family with Congenital Erythrocytosis Caused by Haemoglobin Bethesda. AB - We herein present a case of congenital erythrocytosis caused by haemoglobin (Hb) Bethesda in a Japanese family. A 55-year-old asymptomatic man was referred to our hospital for the investigation of erythrocytosis, which was present in other members of his family. The patient's serum erythropoietin level was normal, and the JAK2 V617F mutation was not detected. His P50 value was mildly decreased, thus we suspected the presence of an Hb variant with a high oxygen affinity. The high-performance liquid chromatography analysis showed an abnormal Hb, and by direct sequencing we identified the Hb Bethesda variant in this patient. For the differential diagnosis, we recommend the estimation of the P50 value as a practical and useful test. PMID- 26370868 TI - Polycythemia Vera Diagnosed after Esophageal Variceal Rupture. AB - Polycythemia vera (PV) is a chronic myeloproliferative neoplasm that leads to hyperviscosity and the risk of thrombosis. We encountered the case of a young male Filipino patient diagnosed with PV after the rupture of esophageal varices. The complete blood cell count showed a slight increase in white blood cells. An abdominal computed tomography scan disclosed splenomegaly and occlusion of the portal vein and collateral vessels. A blood examination demonstrated an increase in all three blood cell lines within three months. Based on the presence of severe hypercellularity of the bone marrow and positivity for the JAK2V617F mutation, we finally diagnosed the patient with PV. PMID- 26370869 TI - Endogenous Endophthalmitis Following Streptococcus pneumoniae Meningitis. AB - A 67-year-old man was transported to our hospital and diagnosed with pneumococcal meningitis. We immediately administered ceftriaxone and vancomycin according to the guidelines, but did not administer dexamethasone to him because he had been previously administered antibiotics. His left eye became complicated by endogenous endophthalmitis on the next day, which resulted in blindness, although his meningitis rapidly ameliorated. In comparison to other patients who have been reported to recover from complications with endophthalmitis after the combination therapy of antibiotics, corticosteroids and vitreous surgery, we consider that this patient's poor visual outcome may have been caused by severe inflammation or the breakdown of the blood ocular barrier due to the action of S. pneumoniae. Corticosteroids may be able to successfully treat such inflammation or disruption of the blood ocular barrier. PMID- 26370871 TI - Fallopian Tube Cancer with Palmar Fibromatosis or Fasciitis without Polyarthritis. AB - A 64-year-old Japanese woman had rapidly progressing bilateral palmar contracture associated with severe pain on both palms over the previous 8 weeks, without a history of arthritis in any joints. We suspected palmar fibromatosis or fasciitis without polyarthritis. Because palmar fibromatosis is known to be associated with cancer, we performed cancer screening and the patient was subsequently diagnosed with fallopian tube cancer. This is the first case report of palmar fibromatosis or fasciitis without polyarthritis associated with fallopian tube cancer. The characteristic rapid progression of palmar contracture is a key finding that suggests the potential existence of a malignancy. PMID- 26370870 TI - Crowned Dens Syndrome as an Initial Manifestation of Crystalline Deposition Disease. AB - An 88-year-old woman presented with fever and acute posterior neck pain. A CT scan revealed calcification of the transverse ligament and crown-like calcification around the odontoid process. According to the clinical and radiological findings, she was diagnosed with crowned dens syndrome (CDS). Her symptoms drastically improved following treatment with oral nonsteroidal anti inflammatory medication. An X-ray of her wrist, elbow, shoulder and knee joints showed asymptomatic calcium deposits, suggesting underlying crystalline deposition disease. CDS may occur as the initial presentation of crystalline deposition disease. The measurement of procalcitonin and an X-ray survey of the major joints may be helpful for the diagnosis of CDS. PMID- 26370872 TI - Pyogenic Spondylitis and Diskitis Caused by Helicobacter cinaedi in an Immunocompetent Adult Patient. AB - We herein describe the first reported case of pyogenic spondylitis and diskitis caused by Helicobacter cinaedi. The results of magnetic resonance imaging and the histology of biopsied tissue were suggestive of acute infection at the lumbar spine. The pathogen was obtained by a blood culture examination and identified by 16S rRNA analysis. Eight weeks of antibiotics therapy resulted in a good clinical course. H. cinaedi infections have been increasingly reported in recent years, but the pathogen's epidemiological and pathological characteristics are still unclear. One of the difficulties in understanding the pathogenesis of H. cinaedi has been the challenges in cultivating the pathogen. Novel strategies for the diagnosis of H. cinaedi must be developed. PMID- 26370873 TI - Asymptomatic Saccular Aneurysm of the Superior Vena Cava. PMID- 26370874 TI - Hyperintense Lesion in the Pons in Intravascular Lymphoma. PMID- 26370875 TI - HIV Encephalopathy as an Initial Manifestation of AIDS. PMID- 26370876 TI - Purpura Fulminans due to Enterobacter cloacae. PMID- 26370877 TI - Interankle systolic blood pressure difference and renal outcomes in patients with chronic kidney disease. AB - AIM: Interankle blood pressure (BP) difference has been associated with peripheral artery disease and adverse cardiovascular outcomes. However, the relationship between interankle BP difference and renal outcomes in chronic kidney disease (CKD) has never been evaluated. The purpose of this study was to determine whether interankle BP difference is associated with the rate of renal function decline and progression to renal end points in patients with stage 3-5 CKD. METHODS: We enrolled 144 patients with CKD from one regional hospital. The BP in four limbs was simultaneously measured using an ABI-form device. The decline in renal function was evaluated using an estimated glomerular filtration rate (eGFR) slope. Rapid renal progression was defined as an eGFR slope < -3 mL/min per 1.73 m(2) per year. The renal end points were defined as >= 25% decline in eGFR or commencement of dialysis during the follow-up period. RESULTS: During a mean follow-up period of 3.1 years, 90 patients (62.5%) reached renal end points. Multivariate analysis showed that an increased interankle systolic BP difference (per 5 mmHg) was associated with a worse eGFR slope (regression beta, 0.292; 95% confidence interval [CI], -0.482 to -0.102; P = 0.003), rapid renal progression (odds ratio, 1.189; 95% CI, 1.015-1.394; P = 0.032), and an increased risk of progression to renal end points (hazard ratio, 1.126; 95% CI, 1.052 1.204, P = 0.001). CONCLUSION: Interankle systolic BP difference was associated with rapid renal progression and progression to renal end points in patients with stage 3-5 CKD in our study. PMID- 26370878 TI - Self-sorting heterodimeric coiled coil peptides with defined and tuneable self assembly properties. AB - Coiled coils with defined assembly properties and dissociation constants are highly attractive components in synthetic biology and for fabrication of peptide based hybrid nanomaterials and nanostructures. Complex assemblies based on multiple different peptides typically require orthogonal peptides obtained by negative design. Negative design does not necessarily exclude formation of undesired species and may eventually compromise the stability of the desired coiled coils. This work describe a set of four promiscuous 28-residue de novo designed peptides that heterodimerize and fold into parallel coiled coils. The peptides are non-orthogonal and can form four different heterodimers albeit with large differences in affinities. The peptides display dissociation constants for dimerization spanning from the micromolar to the picomolar range. The significant differences in affinities for dimerization make the peptides prone to thermodynamic social self-sorting as shown by thermal unfolding and fluorescence experiments, and confirmed by simulations. The peptides self-sort with high fidelity to form the two coiled coils with the highest and lowest affinities for heterodimerization. The possibility to exploit self-sorting of mutually complementary peptides could hence be a viable approach to guide the assembly of higher order architectures and a powerful strategy for fabrication of dynamic and tuneable nanostructured materials. PMID- 26370879 TI - Consider the Support Worker in the Role of Health Assessments. PMID- 26370880 TI - Phacomatosis spilorosea: visual diagnosis and associated pathologies of a rare entity. PMID- 26370881 TI - Impact of prolonged sitting on vascular function in young girls. AB - NEW FINDINGS: What is the central question of this study? Children are spending more than 60% of their waking day sedentary. The consequences of excessive sedentary behaviour are not well understood in the child, but there is growing evidence that with increasing sedentary time, cardiovascular risk in childhood also increases. What is the main finding and its importance? Our findings show that a 3 h period of uninterrupted sitting causes a profound (33%) reduction in vascular function in young girls. Importantly, we also demonstrate that breaking up sitting with regular exercise breaks can prevent this. Excessive sedentary behaviour has serious clinical and public health implications; however, the physiological changes that accompany prolonged sitting in the child are not completely understood. Herein, we examined the acute effect a prolonged period of sitting has upon superficial femoral artery function in 7- to 10-year-old girls and the impact of interrupting prolonged sitting with exercise breaks. Superficial femoral artery endothelium-dependent flow-mediated dilatation, total shear rate, anterograde and retrograde shear rates and oscillatory shear index were assessed before and after two experimental conditions: a 3 h uninterrupted period of sitting (SIT) and a 3 h period of sitting interrupted each hour with 10 min of moderate-intensity exercise (EX). A mixed-model analysis of variance was used to compare between-condition and within-condition main effects, controlling for the within-subject nature of the experiment by including random effects for participant. Superficial femoral artery endothelium-dependent flow-mediated dilatation decreased significantly from pre- to post-SIT (mean difference 2.2% flow-mediated dilatation; 95% confidence interval = 0.60-2.94%, P < 0.001). This relative decline of 33% was abolished in the EX intervention. Shear rates were not significantly different within conditions. Our data demonstrate the effectiveness of short but regular exercise breaks in offsetting the detrimental effects of uninterrupted sitting in young girls. PMID- 26370882 TI - Cardiovascular Disease Predicts Severe Hypoglycemia in Patients with Type 2 Diabetes. AB - BACKGROUND: To investigate whether a history of prior cardiovascular disease (CVD) is associated with severe hypoglycemia (SH) in patients with type 2 diabetes. METHODS: We conducted a prospective cohort study from January 2001 to December 2012 with a median follow-up time of 9.5 years (5,814 person-years). Patients aged 25 to 75 years with type 2 diabetes and without chronic kidney disease were enrolled (n=894), and 624 patients completed follow-up. SH was defined as hypoglycemic episodes requiring hospitalization or medical care in an emergency department. We used the Cox proportional hazards regression analysis to test associations between SH episodes and potential explanatory variables. RESULTS: Among the 624 participants who completed follow-up, 60 patients (9.6%) had previous CVD. Compared to patients without CVD, patients with previous CVD were older, had a longer duration of diabetes and hypertension, received more insulin, and had more diabetic microvascular complications at baseline. During follow-up, 62 patients (9.9%) experienced at least one SH episode (incidence of 1.33 per 100 patient-years). The development of SH was associated with a history of CVD (hazard ratio, 1.99; 95% confidence interval, 1.07 to 3.72; P=0.031) after adjusting for sex, age, diabetic duration, hypertension, hemoglobin A1c levels, diabetic complications, cardiovascular autonomic neuropathy, and insulin use. CONCLUSION: A history of CVD was an independent risk factor for the development of SH in patients with type 2 diabetes mellitus. For patients with CVD, modulation of glycemic targets and diabetic education for the prevention of hypoglycemia should be implemented. PMID- 26370890 TI - Maternal Obesity During Pregnancy Associates With Premature Mortality and Major Cardiovascular Events in Later Life. AB - One in 5 pregnant women is obese but the impact on later health is unknown. We aimed to determine whether maternal obesity during pregnancy associates with increased premature mortality and later life major cardiovascular events. Maternity records of women who gave birth to their first child between 1950 and 1976 (n=18 873) from the Aberdeen Maternity and Neonatal databank were linked to the National Register of Deaths, Scotland and Scottish Morbidity Record. The effect of maternal obesity at first antenatal visit on death and hospital admissions for cardiovascular events was tested using time-to-event analysis with Cox proportional hazard regression to compare outcomes of mothers in underweight, overweight, or obese body mass index (BMI) categories compared with normal BMI. Median follow-up was at 73 years. All-cause mortality was increased in women who were obese during pregnancy (BMI>30 kg/m(2)) versus normal BMI after adjustment for socioeconomic status, smoking, gestation at BMI measurement, preeclampsia, and low birth weight (hazard ratio, 1.35; 95% confidence interval, 1.02-1.77). In adjusted models, overweight and obese mothers had increased risk of hospital admission for a cardiovascular event (1.16; 1.06-1.27 and 1.26; 1.01-1.57) compared with normal BMI mothers. Adjustment for parity largely unchanged the hazard ratios (mortality: 1.43, 1.09-1.88; cardiovascular events overweight: 1.17, 1.07-1.29; and obese: 1.30, 1.04-1.62). In conclusion, maternal obesity is associated with increased risk of premature death and cardiovascular disease. Pregnancy and early postpartum could represent an opportunity for interventions to identify obesity and reduce its adverse consequences. PMID- 26370891 TI - Low Plasma Volume in Normotensive Formerly Preeclamptic Women Predisposes to Hypertension. AB - Formerly preeclamptic women are at risk for cardiovascular disease. Low plasma volume may reflect latent hypertension and potentially links preeclampsia with chronic cardiovascular disease. We hypothesized that low plasma volume in normotensive formerly preeclamptic women predisposes to hypertension. We longitudinally studied n=104 formerly preeclamptic women in whom plasma volume was measured 3 to 30 months after the preeclamptic pregnancy. Cardiovascular variables were assessed at 2 points in time (3-30 months postpartum and 2-5 years thereafter). Study population was divided into low plasma volume (<=1373 mL/m(2)) and normal plasma volume (>1373 mL/m(2)). Primary end point was hypertension at the second visit: defined as >=140 mm Hg systolic or >=90 mm Hg diastolic. Secondary outcome of this study was change in traditional cardiovascular risk profile between visits. Variables correlating univariately with change in blood pressure between visits were introduced in regression analysis. Eighteen of 104 (17%) formerly preeclamptic women who were normotensive at first visit had hypertension at second evaluation 2 to 5 years later. Hypertension developed more often in women with low plasma volume (10/35 [29%]) than in women with normal plasma volume (8/69 [12%]; odds ratio, 3.2; 95% confidence interval, 1.4-8.6). After adjustments, relationship between plasma volume status and subsequent hypertension persisted (adjusted odds ratio, 3.0; 95% confidence interval, 1.1 8.5). Mean arterial pressure at second visit correlated inverse linearly with plasma volume (r=-0.49; P<0.01). Initially normotensive formerly preeclamptic women have 17% chance to develop hypertension within 5 years. Women with low plasma volume have higher chance to develop hypertension than women with normal plasma volume. Clinically, follow-up of blood pressure seems warranted in women with history of preeclampsia, even when initially normotensive. PMID- 26370892 TI - Role of the Paraventricular Nucleus of the Hypothalamus in the Sympathoexcitatory Effects of Leptin. AB - Leptin binds to receptors in multiple hypothalamic nuclei to increase sympathetic nerve activity; however, the neurocircuitry is unclear. Here, using anesthetized male Sprague-Dawley rats, we investigated the role of the paraventricular nucleus of the hypothalamus. Intracerebroventricular injection of leptin slowly increased lumbar sympathetic nerve activity (LSNA), heart rate, mean arterial pressure, and baroreflex control of LSNA and heart rate. Inhibition of the paraventricular nucleus with muscimol completely reversed leptin's effects. Blockade of paraventricular melanocortin 3/4 receptors with SHU9119 or ionotropic glutamate receptors with kynurenate, alone or together, each partially reversed the effects of leptin, implicating increased activation of glutamate and melanocortin 3/4 receptors. Conversely, although blockade of neuropeptide Y Y1 receptors in the paraventricular nucleus increased LSNA, mean arterial pressure, and heart rate, these responses were prevented by intracerebroventricular or arcuate nucleus injections of leptin, suggesting that, at least in part, leptin also increases sympathetic nerve activity by suppression of tonic neuropeptide Y inhibitory inputs from the arcuate nucleus. Injection of the melanocortin 3/4 receptor agonist melanotan-II into the paraventricular nucleus increased LSNA, mean arterial pressure, and heart rate only after blockade of neuropeptide Y Y1 receptors. Therefore, we conclude that leptin increases LSNA in part via increased glutamatergic and alpha-melanocyte-stimulating hormone drive of paraventricular sympathoexcitatory neurons, the latter of which requires simultaneous withdrawal of tonic neuropeptide Y inhibition. PMID- 26370894 TI - Prevalence and correlates of depression and anxiety among patients with tuberculosis at WolaitaSodo University Hospital and Sodo Health Center, WolaitaSodo, South Ethiopia, Cross sectional study. AB - BACKGROUND: Anxiety and depression are frequently and highly occurring mental disorders in patients with tuberculosis. When depression and anxiety co-morbid with tuberculosis, it leads to poor adherence to anti TB medication, which is important barrier to global control of tuberculosis & increases the risk of morbidity and mortality due to TB. Cross sectional study was conducted to assess prevalence and correlates of depression and anxiety among patients with TB at WolaitaSodo University Hospital and Sodo Health Center, WolaitaSodo, Ethiopia. METHODS: Institution based cross-sectional study was conducted in 2014.A total of 417 TB patients, who had regular follow up at WolaitaSodo University Hospital and Sodo Health Center, WolaitaSodo, South Ethiopia, were recruited to assess depression and anxiety and its associated correlates. Depression and anxiety were assessed through face to face interviews by trained psychiatry nurses using the hospital anxiety and depression scale (HADS). Correlates for depression and anxiety were assessed using a structured questionnaire, Oslo social support scale and TB stigma Scale. RESULTS: The prevalence of depression and anxiety among patients with TB were 43.4% (181) and 41.5% (173) respectively. When we adjusted for the effect of potential confounding variables, patients who had co-morbid HIV infection [AOR = 5.90,(95% CI: 2.34,15.93)], poor social support [AOR = 18.06, (95% CI:11.21,25.45)] & perceived TB stigma [AOR = 10.86, (95% CI:10.26,23.47)] were more likely to have depression as compared to individuals who had no co morbid HIV infection, good social support and no perceived TB stigma respectively. Patients who had co-morbid HIV infection [AOR = 9.61,(95% CI:3.56,25.96)], poor social support [AOR = 8.93,(95% CI: 5.01,15.94)], perceived TB stigma [AOR = 3.11,(95% CI:1.78,5.42)], being female [AOR = 1.72 (95% CI: 1.06, 2.95)], current substance use[AOR = 4.88, (95% CI: 1.79, 13.28)] and being on intensive phase of TB treatment [AOR = 1.91, (95% CI: 1.08, 3.39)] were more likely to have anxiety as compared to individuals who had no co-morbid HIV infection, good social support, no perceived TB stigma, being male and being on continuous phase of TB treatment respectively. CONCLUSION: Developing guidelines and training of health workers in TB clinics is useful to screen and treat depression and anxiety among TB patients. PMID- 26370893 TI - Theory-Driven Longitudinal Study Exploring Indoor Tanning Initiation in Teens Using a Person-Centered Approach. AB - BACKGROUND: Younger indoor tanning initiation leads to greater melanoma risk due to more frequent and persistent behavior. Despite this, there are no published studies exploring the predictors of indoor tanning initiation in teen populations. PURPOSE: This longitudinal study uses latent profile analysis to examine indoor tanning initiation in indoor tanning risk subgroups from a national sample of female adolescents. METHODS: Latent profile analysis used indoor tanning beliefs and perceptions to identify indoor tanning initiation risk subgroups. The teens in each subgroup were reassessed on indoor tanning initiation after a year. RESULTS: Three subgroups were identified: a low risk, anti-tanning subgroup (18.6 %) characterized by low scores on positive indoor tanning belief scales and high scores on beliefs about indoor tanning dangers; a moderate risk aware social tanner subgroup (47.2 %) characterized by high scores on positive indoor tanning belief scales but also high scores on beliefs about indoor tanning dangers; and a high risk risky relaxation tanner subgroup (34.2 %) characterized by high scores on positive indoor tanning belief scales and low scores on beliefs about indoor tanning dangers. Teens in the aware social tanner and risky relaxation tanner subgroups were significantly more likely to initiate indoor tanning in the following year. CONCLUSIONS: These findings highlight the need to identify teens at risk for indoor tanning initiation and develop tailored interventions that will move them to the lowest risk subgroup. Subgroup correlates suggest parent and peer-based interventions may be successful. PMID- 26370896 TI - Acute mental health service delivery to Indigenous women: What is known? AB - The Australian College of Mental Health Nurses directs that mental health nurses must 'enable cultural safety in practice, taking into account age, gender, spirituality, ethnicity and health values'. The present study is a review of the existing literature undertaken in order to identify current knowledge and knowledge gaps regarding the experience of Indigenous women in acute mental health inpatient facilities. In particular, studies that identified environments and practices promoting the development of culturally-safe healing spaces for Indigenous women, and studies that identified women's experience of seclusion, were sought. The results showed that there is little literature directly relevant to Indigenous women's experiences of inpatient mental health units in Australia. The present study consolidates existing knowledge and knowledge gaps, and advances the argument for gender-disaggregated future research. Implications for professional practice and service development are also noted. PMID- 26370897 TI - Preface. Novel targets and drugs to prevent atherogenesis and its consequences. PMID- 26370895 TI - Antibiotic-impregnated cement spacer as definitive management for osteomyelitis. AB - BACKGROUND: Osteomyelitis is a challenge for orthopaedic surgeons. There is a lack of scientific evidence to guide treatment. The purpose of this study was to report the clinical outcome of unplanned retention of antibiotic-impregnated cement spacer (ACS) in the management of osteomyelitis. METHODS: Eight patients (7 with tibial infections and 1 with a calcaneal infection) with osteomyelitis received radical debridement and insertion of an ACS into the bone defect as the definitive management. The mean follow-up period was 2 years (6 months to 4 years). All of these patients had a cement spacer in place. RESULTS: No patient exhibited radiographic evidence of excessive bone loss. The patients reported no or occasional mild pain and exhibited complete weight-bearing abilities, with the exception of one patient who required a crutch because of a spinal cord injury. Signs of recurrence of the osteomyelitis were not noted in any of the patients, and no fractures occurred at last follow-up. CONCLUSION: Our study suggests that a proportion of patients with unplanned retention of ACS appear to function well without necessarily requiring further surgical intervention. PMID- 26370898 TI - Entrainment of prosody in the interaction of mothers with their young children - ERRATUM. PMID- 26370900 TI - Using human genetics to make new medicines. AB - Jeffrey Barrett, Ian Dunham and Ewan Birney discuss the initiatives of the newly founded Centre for Therapeutic Target Validation, including a range of approaches to use human genetics to inform drug discovery and make better medicines. PMID- 26370899 TI - R loops: new modulators of genome dynamics and function. AB - R loops are nucleic acid structures composed of an RNA-DNA hybrid and a displaced single-stranded DNA. Recently, evidence has emerged that R loops occur more often in the genome and have greater physiological relevance, including roles in transcription and chromatin structure, than was previously predicted. Importantly, however, R loops are also a major threat to genome stability. For this reason, several DNA and RNA metabolism factors prevent R-loop formation in cells. Dysfunction of these factors causes R-loop accumulation, which leads to replication stress, genome instability, chromatin alterations or gene silencing, phenomena that are frequently associated with cancer and a number of genetic diseases. We review the current knowledge of the mechanisms controlling R loops and their putative relationship with disease. PMID- 26370903 TI - Evolutionary genetics: Red Queen dynamics in fruit fly sex. PMID- 26370901 TI - Integrating circadian dynamics with physiological processes in plants. AB - The plant circadian clock coordinates the responses to multiple and often simultaneous environmental challenges that the sessile plant cannot avoid. These responses must be integrated efficiently into dynamic metabolic and physiological networks essential for growth and reproduction. Many of the output pathways regulated by the circadian clock feed back to modulate clock function, leading to the appreciation of the clock as a central hub in a sophisticated regulatory network. In this Review, we discuss the circadian regulation of growth, flowering time, abiotic and biotic stress responses, and metabolism, as well as why temporal 'gating' of these processes is important to plant fitness. PMID- 26370904 TI - Influence of implant neck design on facial bone crest dimensions in the esthetic zone analyzed by cone beam CT: a comparative study with a 5-to-9-year follow-up. AB - AIM: To examine the influence of two different neck designs on facial bone crest dimensions in esthetic single implant sites after a 5-to-9-year follow-up analyzed by cone beam computed tomography (CBCT). MATERIALS AND METHODS: Sixty one patients with an implant-borne single crown following early implant placement in the esthetic zone were enrolled. The test group consisted of a bone level (BL) neck design exhibiting a hydrophilic micro-rough surface combined with a platform switching interface (PS) (n = 20). The control group comprised a soft tissue level (STL) neck design exhibiting a hydrophobic machined surface with a matching butt-joint interface (n = 41). Standardized clinical, radiologic, and esthetic parameters were applied. The facial bone crest dimensions were assessed by CBCT. RESULTS: Soft tissue parameters and pink esthetic scores yielded no significant differences between the two designs. Major differences were only observed at the implant shoulder level. The height of the facial bone crest for the BL design was located 0.2 mm above the implant shoulder level, whereas for the STL design, its location was 1.6 mm below. The width of the peri-implant saucer-like bone defect was reduced by 40% for the BL implant design. No differences were observed 2 mm below the shoulder level. CONCLUSIONS: The results of this comparative study suggest better crestal bone stability on the facial aspect of single implant sites in the esthetic zone for a BL design with a platform-switching concept when compared with STL implants with a butt-joint interface. PMID- 26370902 TI - Eco-Evo-Devo: developmental symbiosis and developmental plasticity as evolutionary agents. AB - The integration of research from developmental biology and ecology into evolutionary theory has given rise to a relatively new field, ecological evolutionary developmental biology (Eco-Evo-Devo). This field integrates and organizes concepts such as developmental symbiosis, developmental plasticity, genetic accommodation, extragenic inheritance and niche construction. This Review highlights the roles that developmental symbiosis and developmental plasticity have in evolution. Developmental symbiosis can generate particular organs, can produce selectable genetic variation for the entire animal, can provide mechanisms for reproductive isolation, and may have facilitated evolutionary transitions. Developmental plasticity is crucial for generating novel phenotypes, facilitating evolutionary transitions and altered ecosystem dynamics, and promoting adaptive variation through genetic accommodation and niche construction. In emphasizing such non-genomic mechanisms of selectable and heritable variation, Eco-Evo-Devo presents a new layer of evolutionary synthesis. PMID- 26370905 TI - Diverse recruitment strategies result in different participation percentages in a web-based study, but in similar compliance. AB - OBJECTIVES: We compared participation and compliance with a web-based data collection on infections among population-based samples recruited in different ways. METHODS: Individuals were recruited from participants in the German National Cohort study (Group A, n = 279) or persons who were invited to this study but did not participate (Group B, n = 53). A third group was invited to the web-based study only (Group C, n = 145). RESULTS: Response varied among groups between 3 % (B), 11 % (C) and 61 % (A), but compliance was similar (81-85 %). Response did not differ by age and sex. Compliance was lower among the youngest and oldest participants. In addition, participants currently not employed were more likely to have better compliance. Semi-parametric group-based modelling identified three distinct compliance trajectories; "poor compliance" (8 %), "improving compliance" (14 %) and "very good compliance" (78 %). CONCLUSIONS: Participation differed among modes of recruitment, but compliance was similar among groups and notably high. Different recruitment approaches can be used and collected data can be combined to achieve greater sample sizes for longitudinal web-based studies. PMID- 26370906 TI - Niacin as antidyslipidemic drug. AB - Niacin is an important vitamin (B3) that can be used in gram doses to positively modify pathogenetically relevant lipid disorders: elevated LDL cholesterol, elevated non-HDL cholesterol, elevated triglycerides, elevated lipoprotein(a), and reduced HDL cholesterol. This review reports the latest published findings with respect to niacin's mechanisms of action on these lipids and its anti inflammatory and anti-atherosclerotic effects. In the pre-statin era, niacin was shown to have beneficial effects on cardiovascular end-points; but in recent years, two major studies performed in patients whose LDL cholesterol levels had been optimized by a statin therapy did not demonstrate an additional significant effect on these end-points in the groups where niacin was administered. Both studies have several drawbacks that suggest that they are not representative for other patients. Thus, niacin still plays a role either as an additive to a statin or as a substitute for a statin in statin-intolerant patients. Moreover, patients with elevated triglyceride and low HDL cholesterol levels and patients with elevated lipoprotein(a) concentrations will possibly benefit from niacin, although currently the study evidence for these indications is rather poor. Niacin may be useful for compliant patients, however possible side effects (flushing, liver damage) and contraindications should be taken into consideration. PMID- 26370907 TI - The reversal of antineoplastic drug resistance in cancer cells by beta-elemene. AB - Multidrug resistance (MDR), defined as the resistance of cancer cells to compounds with diverse structures and mechanisms of actions, significantly limits the efficacy of antitumor drugs. A major mechanism that mediates MDR in cancer is the overexpression of adenosine triphosphate (ATP)-binding cassette transporters. These transporters bind to their respective substrates and catalyze their efflux from cancer cells, thereby lowering the intracellular concentrations of the substrates and thus attenuating or even abolishing their efficacy. In addition, cancer cells can become resistant to drugs via mechanisms that attenuate apoptosis and cell cycle arrest such as alterations in the p53, check point kinase, nuclear factor kappa B, and the p38 mitogen-activated protein kinase pathway. In this review, we discuss the mechanisms by which beta-elemene, a compound extracted from Rhizoma zedoariae that has clinical antitumor efficacy, overcomes drug resistance in cancer. PMID- 26370909 TI - Response of sex ratio to timing of breeding in the small cyprinid Gnathopogon caerulescens. AB - The influence of hatching date on the sex ratio of wild Gnathopogon caerulescens was examined. Cohorts reared from eggs collected in the early and middle parts of the spawning season showed almost balanced sex ratios, with female bias in some cohorts. Cohorts born later in the season mostly displayed male bias, and the mean proportion of males later in the season was significantly higher than in early- and mid-season cohorts. These results indicate that the sex ratio of G. caerulescens changes with the time of breeding, increasing along with the ambient water temperature of the lake. PMID- 26370908 TI - A patient-centred approach to biological treatment decision making for psoriasis: an expert consensus. AB - BACKGROUND: Each individual psoriasis patient has different expectations and goals for biological treatment, which may differ from those of the clinician. As such, a patient-centred approach to treatment goals remains an unmet need in psoriasis. OBJECTIVE: The aim of this study was to review available data on patients' and physicians' decision criteria and expectations of biological treatment for moderate-to-severe psoriasis with the aim of developing a core set of questions for clinicians to ask patients routinely to understand what is important to them and thus better align physicians' and patients' expectations of treatment with biologics and its outcomes. METHODS: A literature search was conducted to identify key themes and data gaps. Aspects of treatment relevant when choosing a biological agent for an individual patient were identified and compared to an existing validated instrument. A series of questions aimed at helping the physician to identify the particular aspects of treatment that are recognised as important to individual psoriasis patients was developed. RESULTS: Key findings of the literature search were grouped under themes of adherence, decision-making, quality of life, patient/physician goals, communication, patient reported outcomes, satisfaction and patient benefit index. Several aspects of treatment were identified as being relevant when choosing a biological agent for an individual patient. The questionnaire is devised in two parts. The first part asks questions about patients' experience of psoriasis and satisfaction with previous treatments. The second part aims to identify the treatment attributes patients consider to be important and may as such affect their preference for a particular biological treatment. The questionnaire results will allow the physician to understand the key factors that can be influenced by biological drug choice that are of importance to the patient. This information can be used be the physician in clinical decision making. CONCLUSION: The questionnaire has been developed to provide a new tool to better understand and align patients' and physicians' preferences and goals for biological treatment of psoriasis. PMID- 26370910 TI - Pharmacokinetics, Pharmacodynamics, and Efficacy of a Novel Long-Acting Human Growth Hormone: Fc Fusion Protein. AB - The current recombinant human growth hormone (rhGH) therapy requires daily subcutaneous (sc) injections, which results in poor patient compliance, especially in young children. To reduce the dosing frequency, we generated a chimeric protein of rhGH and the Fc-domain of immunoglobulin G (IgG) (rhGH-Fc). The pharmacokinetics and pharmacodynamics of sc-injected rhGH-Fc were assessed in male Sprague-Dawley rats and hypophysectomized rats, respectively. A single sc injection of rhGH-Fc at a dose of 0.2 mg/kg slowly reached a Cmax of 16.80 ng/mL and remained for 7 days with a half-life of 51.1 h. Conversely, a single sc injection of rhGH 0.2 mg/kg rapidly reached a Cmax of 46.88 ng/mL and declined with a half-life of 0.55 h to baseline values in 4 h. In the efficacy study, the sc-injected rhGH-Fc induced rapid weight gain and tibial width growth at a dose of 240 MUg/animal. The effect of two injections of rhGH-Fc separated by 1 week was comparable to that of the same dose of 14 daily injections of rhGH. The rhGH Fc is a novel candidate for long-acting rhGH therapy with more convenient weekly administration, as it reduces glomerular filtration and receptor-mediated clearance while allowing for the rapid reversal of potential adverse events. PMID- 26370911 TI - Study supports more aggressive blood pressure treatment targets, US officials say. PMID- 26370913 TI - A stop-gain in the laminin, alpha 3 gene causes recessive junctional epidermolysis bullosa in Belgian Blue cattle. AB - Four newborn purebred Belgian Blue calves presenting a severe form of epidermolysis bullosa were recently referred to our heredo-surveillance platform. SNP array genotyping followed by autozygosity mapping located the causative gene in a 8.3-Mb interval on bovine chromosome 24. Combining information from (i) whole-genome sequencing of an affected calf, (ii) transcriptomic data from a panel of tissues and (iii) a list of functionally ranked positional candidates pinpointed a private G to A nucleotide substitution in the LAMA3 gene that creates a premature stop codon (p.Arg2609*) in exon 60, truncating 22% of the corresponding protein. The LAMA3 gene encodes the alpha 3 subunit of the heterotrimeric laminin-332, a key constituent of the lamina lucida that is part of the skin basement membrane connecting epidermis and dermis layers. Homozygous loss-of-function mutations in this gene are known to cause severe junctional epidermolysis bullosa in human, mice, horse, sheep and dog. Overall, our data strongly support the causality of the identified gene and mutation. PMID- 26370912 TI - Paradoxical effects of partial leptin deficiency on bone in growing female mice. AB - Morbidly obese, leptin-deficient ob/ob mice display low bone mass, mild osteoclast-rich osteopetrosis, and increased bone marrow adiposity. While partial leptin deficiency results in increased weight, the skeletal manifestations of partial leptin deficiency are less well defined. We therefore analyzed femora and lumbar vertebrae in growing (7-week-old) female C57BL/6 wildtype (WT) mice, partial leptin-deficient ob/+ mice, and leptin-deficient ob/ob mice. The bones were evaluated by dual energy absorptiometry, microcomputed tomography and histomorphometry. As expected, ob/+ mice were heavier, had more white adipose tissue, and lower serum leptin than WT mice, but were lighter and had less white adipose tissue than ob/ob mice. With a few exceptions, cancellous bone architecture, cell (osteoblast, osteoclast, and adipocyte), and dynamic measurements did not differ between WT and ob/+ mice. In contrast, compared to WT and ob/+ mice, ob/ob mice had lower cancellous bone volume fraction, and higher bone marrow adiposity in the femur metaphysis, and higher cancellous bone volume fraction in lumbar vertebra. Paradoxically, ob/+ mice had greater femoral bone volume than either WT or ob/ob mice. There was a positive correlation between body weight and femur volume in all three genotypes. However, the positive effect of weight on bone occurred with lower body weight in leptin-producing mice. The paradoxical differences in bone size among WT, ob/+, and ob/ob mice may be explained if leptin, in addition to stimulating bone growth and cancellous bone turnover, acts to lower the set-point at which increased body weight leads to a commensurate increase in bone size. PMID- 26370914 TI - Palmitoylethanolamide attenuates PTZ-induced seizures through CB1 and CB2 receptors. AB - Epilepsy is one of the most common neurologic disorders. Though there are effective medications available to reduce the symptoms of the disease, their side effects have limited their usage. Palmitoylethanolamide (PEA) has been shown to attenuate seizure in different animal models. The objective of the current study was to evaluate the role of CB1 and CB2 receptors in this attenuation. Male wistar rats were used for the current experiment. PTZ was injected to induce chemical kindling in animals. After verification of kindling in animals, treatment was performed with PEA, AM251 and AM630 in different groups. Latency to induce seizure, seizure stages and latency and duration of fifth stage of seizure was recorded for each animal. Injection of PTZ led to seizure in the animals. Pretreatment with PEA increased the latency to initiate seizures and reduced the duration of seizure. Pretreatment with different dosages of AM251 had contrary effects so that at lower doses they increased the seizure in animals but at higher doses led to the attenuation of seizure. AM630 increased seizures in a dose dependent manner. Combination of the antagonists increased the seizure parameters and attenuated the effect of PEA on seizure. PEA attenuated the PTZ induced seizures and pretreatment with CB1 and CB2 antagonists diminished this effect of PEA, but still PEA was effective, which might be attributed to the contribution of other receptors in PEA anti-epileptic properties. Findings of the current study implied that endocannabinoid signaling pathway might have an important role in the effects of PEA. PMID- 26370915 TI - Morphometric MRI analysis enhances visualization of cortical tubers in tuberous sclerosis. AB - PURPOSE: Focal cortical dysplasias (FCD) type IIb and cortical tubers in tuberous sclerosis complex (TSC) are histopathologically similar and are both epileptogenic lesions frequently causing pharmacoresistant epilepsies. Morphometric analysis of T1- and T2-weighted MRI volume data sets can enhance visualization of FCD. Here, we retrospectively investigated whether morphometric MRI analysis is of equal benefit for visualizing cortical tubers. MATERIALS AND METHODS: Morphometric analysis was applied to T1- and partly also T2-weighted 1.5T or 3T MRI volume data sets of 15 TSC patients using a fully automated MATLAB((r)) script (i.e. MAP07) commonly used for FCD detection. In this study, focus was on the most sensitive of the resulting morphometric feature maps (i.e. the 'junction image') which highlights blurring of the gray-white matter junction in comparison to a normal database. The visualization of tubers in these 'junction images' was quantitatively compared with that in conventional MR sequences. RESULTS: In all patients, morphometric analysis visualized almost all tubers detected in the normal MRI, and additionally highlighted on average 23% (range 3-50%) more tubers which were not detected by visual analysis of the conventional MR sequences. When T2 volume data sets from a 3T scanner were available for postprocessing, the rate of additionally detected tubers increased to 29% on average. These formerly overlooked tubers were usually smaller than the tubers already found in the conventional MRI. CONCLUSION: Morphometric analysis of MRIs in TSC can highlight cortical tubers which are likely to be overlooked in conventional MRI sequences alone. Additionally detected tubers may be of potential importance for both presurgical evaluation and initial diagnosis of TSC. PMID- 26370916 TI - Association of adherence to epilepsy quality standards with seizure control. AB - OBJECTIVE: We assessed the relationship between adherence to epilepsy quality measures (EQM) and seizure control over 2-3 years in a retrospective cohort study. METHODS: 6150 patients were identified at two large academic medical centers with a primary or secondary diagnosis of epilepsy, were 18-85 years old and seen in outpatient general neurology or epilepsy units between June 2011 and May 2014. Patients were included if: their initial visit was between June 2011 and June 2012, treatment was with >=1 anti-seizure drug, there was >=1 visit per year during the timeframe, and seizure frequency was documented at initial and final visits, yielding 162 patients/1055 visits from which socio-demographic, clinical and care quality data were abstracted. Quality care was assessed as (1) percent adherence to up to 8 eligible EQM, and (2) defect-free care (DFC: adherence to all eligible EQM). Seizure control (SC) was defined as >=50% reduction in average seizures/month between initial and final visits. Chi-square and t-test compared care quality with seizure control. Logistic regression was used to assess the relationships between SC, quality of care and subspecialist involvement. RESULTS: Care quality, reflected by documentation of seizure frequency, addressing therapeutic interventions, and referral to a comprehensive epilepsy center, all exceeded 80% adherence. Care quality as reflected by documentation of seizure type, etiology or syndrome; assessment of side effects, counseling about epilepsy safety and women's issues, and screening for psychiatric disorders ranged from 40 to 57%. Mean EQM adherence across all applicable measures was associated with greater seizure control (p=0.0098). DFC was low (=8%) and did not covary with seizure control (p=0.55). The SC and non-SC groups only differed on epilepsy etiology (p=0.04). Exploratory analysis showed that mean quality scores are associated with seizure control (OR=4.9 [1.3-18.5], p=0.017) while controlling for the effect of subspecialty involvement as a possible confounding variable. CONCLUSIONS: Average quality of care but not defect-free care was associated with seizure control in this retrospective cohort. PMID- 26370917 TI - fMRI brain response during sentence reading comprehension in children with benign epilepsy with centro-temporal spikes. AB - INTRODUCTION: Children with benign epilepsy with centro-temporal spikes (BECTS) often have language problems. Abnormal epileptic activity is found in central and temporal brain regions, which are involved in reading and semantic and syntactic comprehension. Using functional magnetic resonance imaging (fMRI), we examined reading networks in BECTS children with a new sentence reading comprehension task involving semantic and syntactic processing. METHOD: Fifteen children with BECTS (age=11y 1m +/- 16 m; 12 boys) and 18 healthy controls (age=11 y 8m +/- 20 m; 11 boys) performed an fMRI reading comprehension task in which they read a pair of syntactically complex sentences and decided whether the target sentence (the second sentence in the pair) was true or false with respect to the first sentence. All children also underwent an exhaustive neuropsychological assessment. RESULTS: We demonstrated weaknesses in several cognitive domains in BECTS children. During the sentence reading fMRI task, left inferior frontal regions and bilateral temporal areas were activated in BECTS children and healthy controls. However, additional brain regions such as the left hippocampus and precuneus were activated in BECTS children. Moreover, specific activation was found in the left caudate and putamen in BECTS children but not in healthy controls. Cognitive results and accuracy during the fMRI task were associated with specific brain activation patterns. CONCLUSION: BECTS children recruited a wider network to perform the fMRI sentence reading comprehension task, with specific activation in the left dorsal striatum. BECTS cognitive performance differently predicted functional activation in frontal and temporal regions compared to controls, suggesting differences in brain network organisation that contribute to reading comprehension. PMID- 26370918 TI - Baseline Antihypertensive Drug Count and Patient Response to Hypertension Medication Management. AB - Telemedicine-based medication management improves hypertension control, but has been evaluated primarily in patients with low antihypertensive drug counts. Its impact on patients taking three or more antihypertensive agents is not well established. To address this evidence gap, the authors conducted an exploratory analysis of an 18-month, 591-patient trial of telemedicine-based hypertension medication management. Using general linear models, the effect of medication management on blood pressure for patients taking two or fewer antihypertensive agents at study baseline vs those taking three or more was compared. While patients taking two or fewer antihypertensive agents had a significant reduction in systolic blood pressure with medication management, those taking three or more had no such response. The between-subgroup effect difference was statistically significant at 6 months (-6.4 mm Hg [95% confidence interval, -12.2 to -0.6]) and near significant at 18 months (-6.0 mm Hg [95% confidence interval, -12.2 to 0.2]). These findings suggest that baseline antihypertensive drug count may impact how patients respond to hypertension medication management and emphasize the need to study management strategies specifically in patients taking three or more antihypertensive medications. PMID- 26370919 TI - Quantum interference based Boolean gates in dangling bond loops on Si(100):H surfaces. AB - Implementing atomic and molecular scale electronic functionalities represents one of the major challenges in current nano-electronic developments. Engineered dangling bond nanostructures on Silicon or Germanium surfaces posses the potential to provide novel routes towards the development of non-conventional electronic circuits. These structures are built by selectively removing hydrogen atoms from an otherwise fully passivated Si(100) or Ge(100) substrate. In this theoretical study, we demonstrate how dangling bond loops can be used to implement different Boolean logic gates. Our approach exploits quantum interference effects in such ring-like structures combined with an appropriate design of the interfacing of the dangling bond system with mesoscopic electrodes. We show how OR, AND, and NOR gates can be realized by tuning either the global symmetry of the system in a multi-terminal setup-by arranging the position of the input and output electrodes-or, alternatively, by selectively applying electrostatic gates in a two-terminal configuration. PMID- 26370920 TI - Ozone treatment prevents the toxicity of an environmental mixture of estrogens on rat fetal testicular development. AB - Effluents from wastewater treatment plants contain a mixture of estrogens (MIX: 17beta-estradiol: E2, estrone: E1, estriol: E3 and 17alpha-ethinylestradiol EE2). High doses of estrogens have been shown to negatively impact fetal testicular development, but the impact of low doses of estrogens in mixture have yet to be elucidated. Using an organ culture system in which embryonic 15.5 day-old rat testes were grown ex vivo, we showed that exposure to the MIX at environmentally relevant concentrations reduces testis growth. No effect was observed on testosterone secretion, but we quantified a significant decrease in the number of Sertoli cells and gonocytes because of higher rates of apoptosis. As ozone (O3) can be used as a disinfectant during wastewater treatment, we confirmed by HPLC MS analysis that it removes the four parent compounds. Interestingly, the negative effects of the MIX were not observed when testes were exposed to the MIX treated with O3. PMID- 26370921 TI - Comparison of mandibular cortical thickness and QCT-derived bone mineral density (BMD) in survivors of childhood acute lymphoblastic leukemia: a retrospective study. AB - OBJECTIVE: To examine whether panoramic radiograph-determined mandibular cortical thickness correlated with quantitative computed tomography-derived bone mineral density (BMD) in survivors of childhood acute lymphoblastic leukemia (ALL). METHODS: We identified patients treated for ALL at St. Jude Children's Research Hospital, seen in the After Completion of Therapy (ACT) Clinic between January of 2006 and January of 2014 who had QCT-derived BMD and panoramic radiographs obtained within 1 month of each other. Panoramic radiographs were independently scored by a pediatric radiologist, two pediatric dentists, and a general dentist using the Klemetti technique. We used the Spearman's rank correlation test and the multivariate regression model to investigate the effect of evaluator experience on results. RESULTS: The study cohort comprised 181 patients with 320 paired studies: 112 (62%) male, 112 (71%) were white. Median age at ALL diagnosis was 6.4 (range, 0-18.8) years. Median age at study was 11.9 (range, 3.3 to 29.4) years. The median average BMD was 154.6 (range, 0.73-256) mg/cc; median QCT Z score (age and gender adjusted) was -0.875 (range, -5.04 to 3.2). We found very weak association between panoramic radiograph score and both QCT-BMD average (P = 0.53) and QCT Z-score (P = 0.39). Results were not influenced by level of reader experience. CONCLUSIONS: The Klemetti technique of estimating BMD does not predict BMD deficits in children and young adult survivors of ALL, regardless of reviewer expertise. Alternative methods are needed whereby dental healthcare providers can identify and refer patients at risk for BMD deficits for detailed assessment and intervention. PMID- 26370922 TI - Anti-aging Effect of Transplanted Amniotic Membrane Mesenchymal Stem Cells in a Premature Aging Model of Bmi-1 Deficiency. AB - To determine whether transplanted amniotic membrane mesenchymal stem cells (AMSCs) ameliorated the premature senescent phenotype of Bmi-1-deficient mice, postnatal 2-day-old Bmi-1(-/-) mice were injected intraperitoneally with the second-passage AMSCs from amniotic membranes of beta-galactosidase (beta-gal) transgenic mice or wild-type (WT) mice labeled with DiI. Three reinjections were given, once every seven days. Phenotypes of 5-week-old beta-gal(+) AMSC transplanted or 6-week-old DiI(+) AMSC-transplanted Bmi-1(-/-) mice were compared with vehicle-transplanted Bmi-1(-/-) and WT mice. Vehicle-transplanted Bmi-1(-/-) mice displayed growth retardation and premature aging with decreased cell proliferation and increased cell apoptosis; a decreased ratio and dysmaturity of lymphocytic series; premature osteoporosis with reduced osteogenesis and increased adipogenesis; redox imbalance and DNA damage in multiple organs. Transplanted AMSCs carried Bmi-1 migrated into multiple organs, proliferated and differentiated into multiple tissue cells, promoted growth and delayed senescence in Bmi-1(-/-) transplant recipients. The dysmaturity of lymphocytic series were ameliorated, premature osteoporosis were rescued by promoting osteogenesis and inhibiting adipogenesis, the oxidative stress and DNA damage in multiple organs were inhibited by the AMSC transplantation in Bmi-1(-/-) mice. These findings indicate that AMSC transplantation ameliorated the premature senescent phenotype of Bmi-1-deficient mice and could be a novel therapy to delay aging and prevent aging-associated degenerative diseases. PMID- 26370923 TI - Comparison of spironolactone and spironolactone plus metformin in the treatment of polycystic ovary syndrome. AB - The aim of this study was to evaluate and compare the effects of spironolactone and spironolactone plus metformin treatments on body mass index (BMI), hirsutism score, hormone levels, and insulin resistance in women with polycystic ovary syndrome (PCOS). Thirty-seven patients with PCOS were randomly assigned to receive spironolactone 100 mg/d (spironolactone group, 18 patients) or spironolactone 100 mg/d plus metformin 2000 mg/d (combination group, 19 patients) for 12 months. BMI, modified Ferriman-Gallway score (FGS), serum levels of regarding hormones, and homeostasis model assessment of insulin resistance (HOMA IR) index were assessed before and after the treatments. Six patients in the spironolactone group and four patients in the combination group reported inter menstrual vaginal bleeding during treatments. In hirsutism scores, the spironolactone therapy resulted in 25.2% reduction, while combination therapy resulted in 28.3% reduction (p > 0.05, between groups). When the groups were compared in terms of percent changes in BMI, FGS, HOMA-IR, and hormone values other than free testosterone, no significant difference was noted. In the present study, FGSs were significantly decreased in both groups; however, combination therapy was not more effective than spironolactone alone in terms of BMI, FGS, hormone levels, or insulin resistance. PMID- 26370925 TI - [International health experts]. PMID- 26370924 TI - Identification of novel mureidomycin analogues via rational activation of a cryptic gene cluster in Streptomyces roseosporus NRRL 15998. AB - Antimicrobial agents are urgently needed to tackle the growing threat of antibiotic-resistant pathogens. An important source of new antimicrobials is the large repertoire of cryptic gene clusters embedded in microbial genomes. Genome mining revealed a napsamycin/mureidomycin biosynthetic gene cluster in the chromosome of Streptomyces roseosporus NRRL 15998. The cryptic gene cluster was activated by constitutive expression of a foreign activator gene ssaA from sansanmycin biosynthetic gene cluster of Streptomyces sp. strain SS. Expression of the gene cluster was verified by RT-PCR analysis of key biosynthetic genes. The activated metabolites demonstrated potent inhibitory activity against the highly refractory pathogen Pseudomonas aeruginosa, and characterization of the metabolites led to the discovery of eight acetylated mureidomycin analogues. To our surprise, constitutive expression of the native activator gene SSGG_02995, a ssaA homologue in S. roseosporus NRRL 15998, has no beneficial effect on mureidomycin stimulation. This study provides a new way to activate cryptic gene cluster for the acquisition of novel antibiotics and will accelerate the exploitation of prodigious natural products in Streptomyces. PMID- 26370926 TI - Feasibility and acceptability of patient partnership to improve access to primary care for the physical health of patients with severe mental illnesses: an interactive guide. AB - INTRODUCTION: Even in countries with universal healthcare systems, excess mortality rates due to physical chronic diseases in patients also suffering from serious mental illness like schizophrenia is such that their life expectancy could be lessened by up to 20 years. The possible explanations for this disparity include: unhealthy habits (i.e. smoking; lack of exercise); side-effects of psychotropic medication; delays in the detection or initial presentation leading to a more advanced disease at diagnosis; and inequity of access to services. The main objective of this paper is to explore the feasibility and acceptability of patient partnership for developing an interactive guide to improve access to primary care providers for chronic diseases management and health promotion among patients with severe mental illnesses. METHODS: A participatory action research design was used to engage patients with mental illness as full research partners for a strategy for patient-oriented research in primary care for persons with schizophrenia who also have chronic physical illnesses. This strategy was also developed in partnership with a health and social services centre responsible for the health of the population of a territory with about 100,000 inhabitants in East-end Montreal, Canada. A new interactive guide was developed by patient research partners and used by 146 participating patients with serious mental illness who live on this territory, for them to be better prepared for their medical appointment with a General Practitioner by becoming more aware of their own physical condition. RESULTS: Patient research partners produced a series of 33 short videos depicting signs and symptoms of common chronic diseases and risk factors for the leading causes of mortality and study participants were able to complete the corresponding 33-item questionnaire on an electronic touch screen tablet. What proved to be most relevant in terms of interactivity was the dynamic that has developed among the study participants during the small group learning sessions, a training technique designed for healthcare professionals that was adapted for this project for, and with patient partners. CONCLUSION: This research has shown the feasibility and acceptability of patient partnership and patient-oriented research approaches to the R&D process of a new medical tool and intervention for patients with serious mental illness, and its acceptability for addressing inequity of this disadvantaged population in terms of access to primary care providers. PMID- 26370927 TI - Controlled dual delivery of fibroblast growth factor-2 and Interleukin-10 by heparin-based coacervate synergistically enhances ischemic heart repair. AB - Myocardial infarction (MI) causes myocardial necrosis, triggers chronic inflammatory responses, and leads to pathological remodeling. Controlled delivery of a combination of angiogenic and immunoregulatory proteins may be a promising therapeutic approach for MI. We investigated the bioactivity and therapeutic potential of an injectable, heparin-based coacervate co-delivering an angiogenic factor, fibroblast growth factor-2 (FGF2), and an anti-inflammatory cytokine, Interleukin-10 (IL-10) in a spatially and temporally controlled manner. Coacervate delivery of FGF2 and IL-10 preserved their bioactivities on cardiac stromal cell proliferation in vitro. Upon intramyocardial injection into a mouse MI model, echocardiography revealed that FGF2/IL-10 coacervate treated groups showed significantly improved long-term LV contractile function and ameliorated LV dilatation. FGF2/IL-10 coacervate substantially augmented LV myocardial elasticity. Additionally, FGF2/IL-10 coacervate notably enhanced long-term revascularization, especially at the infarct area. In addition, coacervate loaded with 500 ng FGF2 and 500 ng IL-10 significantly reduced LV fibrosis, considerably preserved infarct wall thickness, and markedly inhibited chronic inflammation at the infarct area. These results indicate that FGF2/IL-10 coacervate has notably greater therapeutic potential than coacervate containing only FGF2. Overall, our data suggest therapeutically synergistic effects of FGF-2/IL-10 coacervate, particularly coacervate with FGF2 and 500 ng IL-10, for the treatment of ischemic heart disease. PMID- 26370928 TI - Homogeneous generation of iDA neurons with high similarity to bona fide DA neurons using a drug inducible system. AB - Recent work generating induced dopaminergic (iDA) neurons using direct lineage reprogramming potentially provides a novel platform for the study and treatment Parkinson's disease (PD). However, one of the most important issues for iDA-based applications is the degree to which iDA neurons resemble the molecular and functional properties of their endogenous DA neuron counterparts. Here we report that the homogeneity of the reprogramming gene expression system is critical for the generation of iDA neuron cultures that are highly similar to endogenous DA neurons. We employed an inducible system that carries iDA-inducing factors as defined transgenes for direct lineage reprogramming to iDA neurons. This system circumvents the need for viral transduction, enabling a more efficient and reproducible reprogramming process for the generation of genetically homogenous iDA neurons. We showed that this inducible system generates iDA neurons with high similarity to their bona fide in vivo counterparts in comparison to direct infection methods. Thus, our results suggest that homogenous expression of exogenous genes in direct lineage reprogramming is critical for the generation of high quality iDA neuron cultures, making such culture systems a valuable resource for iDA-based drug screening and, ultimately, potential therapeutic intervention in PD. PMID- 26370929 TI - Characterization of the antioxidant activity of aglycone and glycosylated derivatives of hesperetin: an in vitro and in vivo study. AB - The flavonoids are mainly present in Citrus fruits as their glycosyl derivatives. This study was conducted comparing in vitro xanthine oxidase inhibitory activity of the aglycone hesperetin and its glycosylated forms (hesperidin and G hesperidin) and their effects on the plasma lipid profile and the oxidative antioxidative system (TBARS and antioxidant enzymes) in rats. The concentrations of the major conjugated metabolites in rat plasma after oral administration of these compounds were also determined. Wistar male rats were randomly assigned to three groups (n=6) supplemented for 30 days with 1 mmol/kg body mass of hesperetin, hesperidin or G-hesperidin. Hesperetin was a stronger xanthine oxidase inhibitor (IC50=53 MUM and Ki=17.3 MUM) than the glycosylate derivatives. Supplementation with the three compounds led to a lower (more favorable) atherogenic index, and an antioxidant preventive effect from the increase of hepatic superoxide dismutase was observed associated to HT supplementation, possibly because of the higher level of hesperetin-glucuronide in rat plasma. PMID- 26370930 TI - Can ovarian vein embolization cause more harm than good? AB - Ovarian vein embolization using embolic coils is a recognized treatment for chronic pelvic pain caused by pelvic congestion syndrome (PCS). Although it is considered a non-invasive procedure with a good safety record, there have been reported complications resulting from embolic coil migration. We present a case of embolic coil erosion of the ovarian vein discovered on laparoscopy for chronic pelvic pain. PMID- 26370931 TI - Unambiguous detection of nitrated explosive vapours by fluorescence quenching of dendrimer films. AB - Unambiguous and selective standoff (non-contact) infield detection of nitro containing explosives and taggants is an important goal but difficult to achieve with standard analytical techniques. Oxidative fluorescence quenching is emerging as a high sensitivity method for detecting such materials but is prone to false positives-everyday items such as perfumes elicit similar responses. Here we report thin films of light-emitting dendrimers that detect vapours of explosives and taggants selectively-fluorescence quenching is not observed for a range of common interferents. Using a combination of neutron reflectometry, quartz crystal microbalance and photophysical measurements we show that the origin of the selectivity is primarily electronic and not the diffusion kinetics of the analyte or its distribution in the film. The results are a major advance in the development of sensing materials for the standoff detection of nitro-based explosive vapours, and deliver significant insights into the physical processes that govern the sensing efficacy. PMID- 26370932 TI - The bacterial cell envelope. PMID- 26370934 TI - Type VI secretion system: secretion by a contractile nanomachine. AB - The type VI secretion systems (T6SS) are present in about a quarter of all Gram negative bacteria. Several key components of T6SS are evolutionarily related to components of contractile nanomachines such as phages and R-type pyocins. The T6SS assembly is initiated by formation of a membrane complex that binds a phage like baseplate with a sharp spike, and this is followed by polymerization of a long rigid inner tube and an outer contractile sheath. Effectors are preloaded onto the spike or into the tube during the assembly by various mechanisms. Contraction of the sheath releases an unprecedented amount of energy, which is used to thrust the spike and tube with the associated effectors out of the effector cell and across membranes of both bacterial and eukaryotic target cells. Subunits of the contracted sheath are recycled by T6SS-specific unfoldase to allow for a new round of assembly. Live-cell imaging has shown that the assembly is highly dynamic and its subcellular localization is in certain bacteria regulated with a remarkable precision. Through the action of effectors, T6SS has mainly been shown to contribute to pathogenicity and competition between bacteria. This review summarizes the knowledge that has contributed to our current understanding of T6SS mode of action. PMID- 26370935 TI - Outer membrane protein biogenesis in Gram-negative bacteria. AB - Gram-negative bacteria contain a double membrane which serves for both protection and for providing nutrients for viability. The outermost of these membranes is called the outer membrane (OM), and it contains a host of fully integrated membrane proteins which serve essential functions for the cell, including nutrient uptake, cell adhesion, cell signalling and waste export. For pathogenic strains, many of these outer membrane proteins (OMPs) also serve as virulence factors for nutrient scavenging and evasion of host defence mechanisms. OMPs are unique membrane proteins in that they have a beta-barrel fold and can range in size from 8 to 26 strands, yet can still serve many different functions for the cell. Despite their essential roles in cell survival and virulence, the exact mechanism for the biogenesis of these OMPs into the OM has remained largely unknown. However, the past decade has witnessed significant progress towards unravelling the pathways and mechanisms necessary for moulding a nascent polypeptide into a functional OMP within the OM. Here, we will review some of these recent discoveries that have advanced our understanding of the biogenesis of OMPs in Gram-negative bacteria, starting with synthesis in the cytoplasm to folding and insertion into the OM. PMID- 26370933 TI - Type III secretion systems: the bacterial flagellum and the injectisome. AB - The flagellum and the injectisome are two of the most complex and fascinating bacterial nanomachines. At their core, they share a type III secretion system (T3SS), a transmembrane export complex that forms the extracellular appendages, the flagellar filament and the injectisome needle. Recent advances, combining structural biology, cryo-electron tomography, molecular genetics, in vivo imaging, bioinformatics and biophysics, have greatly increased our understanding of the T3SS, especially the structure of its transmembrane and cytosolic components, the transcriptional, post-transcriptional and functional regulation and the remarkable adaptivity of the system. This review aims to integrate these new findings into our current knowledge of the evolution, function, regulation and dynamics of the T3SS, and to highlight commonalities and differences between the two systems, as well as their potential applications. PMID- 26370936 TI - Bacterial cell wall composition and the influence of antibiotics by cell-wall and whole-cell NMR. AB - The ability to characterize bacterial cell-wall composition and structure is crucial to understanding the function of the bacterial cell wall, determining drug modes of action and developing new-generation therapeutics. Solid-state NMR has emerged as a powerful tool to quantify chemical composition and to map cell wall architecture in bacteria and plants, even in the context of unperturbed intact whole cells. In this review, we discuss solid-state NMR approaches to define peptidoglycan composition and to characterize the modes of action of old and new antibiotics, focusing on examples in Staphylococcus aureus. We provide perspectives regarding the selected NMR strategies as we describe the exciting and still-developing cell-wall and whole-cell NMR toolkit. We also discuss specific discoveries regarding the modes of action of vancomycin analogues, including oritavancin, and briefly address the reconsideration of the killing action of beta-lactam antibiotics. In such chemical genetics approaches, there is still much to be learned from perturbations enacted by cell-wall assembly inhibitors, and solid-state NMR approaches are poised to address questions of cell-wall composition and assembly in S. aureus and other organisms. PMID- 26370937 TI - Channel crossing: how are proteins shipped across the bacterial plasma membrane? AB - The structure of the first protein-conducting channel was determined more than a decade ago. Today, we are still puzzled by the outstanding problem of protein translocation--the dynamic mechanism underlying the consignment of proteins across and into membranes. This review is an attempt to summarize and understand the energy transducing capabilities of protein-translocating machines, with emphasis on bacterial systems: how polypeptides make headway against the lipid bilayer and how the process is coupled to the free energy associated with ATP hydrolysis and the transmembrane protein motive force. In order to explore how cargo is driven across the membrane, the known structures of the protein translocation machines are set out against the background of the historic literature, and in the light of experiments conducted in their wake. The paper will focus on the bacterial general secretory (Sec) pathway (SecY-complex), and its eukaryotic counterpart (Sec61-complex), which ferry proteins across the membrane in an unfolded state, as well as the unrelated Tat system that assembles bespoke channels for the export of folded proteins. PMID- 26370938 TI - A combined kinetic push and thermodynamic pull as driving forces for outer membrane protein sorting and folding in bacteria. AB - In vitro folding studies of outer membrane beta-barrels have been invaluable in revealing the lipid effects on folding rates and efficiencies as well as folding free energies. Here, the biophysical results are summarized, and these kinetic and thermodynamic findings are considered in terms of the requirements for folding in the context of the cellular environment. Because the periplasm lacks an external energy source the only driving forces for sorting and folding available within this compartment are binding or folding free energies and their associated rates. These values define functions for periplasmic chaperones and suggest a biophysical mechanism for the BAM complex. PMID- 26370939 TI - Lipopolysaccharide transport to the cell surface: periplasmic transport and assembly into the outer membrane. AB - Gram-negative bacteria possess an outer membrane (OM) containing lipopolysaccharide (LPS). Proper assembly of the OM not only prevents certain antibiotics from entering the cell, but also allows others to be pumped out. To assemble this barrier, the seven-protein lipopolysaccharide transport (Lpt) system extracts LPS from the outer leaflet of the inner membrane (IM), transports it across the periplasm and inserts it selectively into the outer leaflet of the OM. As LPS is important, if not essential, in most Gram-negative bacteria, the LPS biosynthesis and biogenesis pathways are attractive targets in the development of new classes of antibiotics. The accompanying paper (Simpson BW, May JM, Sherman DJ, Kahne D, Ruiz N. 2015 Phil. Trans. R. Soc. B 370, 20150029. (doi:10.1098/rstb.2015.0029)) reviewed the biosynthesis of LPS and its extraction from the IM. This paper will trace its journey across the periplasm and insertion into the OM. PMID- 26370940 TI - The bacterial divisome: ready for its close-up. AB - Bacterial cells divide by targeting a transmembrane protein machine to the division site and regulating its assembly and disassembly so that cytokinesis occurs at the correct time in the cell cycle. The structure and dynamics of this machine (divisome) in bacterial model systems are coming more clearly into focus, thanks to incisive cell biology methods in combination with biochemical and genetic approaches. The main conserved structural element of the machine is the tubulin homologue FtsZ, which assembles into a circumferential ring at the division site that is stabilized and anchored to the inner surface of the cytoplasmic membrane by FtsZ-binding proteins. Once this ring is in place, it recruits a series of transmembrane proteins that ultimately trigger cytokinesis. This review will survey the methods used to characterize the structure of the bacterial divisome, focusing mainly on the Escherichia coli model system, as well as the challenges that remain. These methods include recent super-resolution microscopy, cryo-electron tomography and synthetic reconstitution. PMID- 26370941 TI - Lipopolysaccharide transport to the cell surface: biosynthesis and extraction from the inner membrane. AB - The cell surface of most Gram-negative bacteria is covered with lipopolysaccharide (LPS). The network of charges and sugars provided by the dense packing of LPS molecules in the outer leaflet of the outer membrane interferes with the entry of hydrophobic compounds into the cell, including many antibiotics. In addition, LPS can be recognized by the immune system and plays a crucial role in many interactions between bacteria and their animal hosts. LPS is synthesized in the inner membrane of Gram-negative bacteria, so it must be transported across their cell envelope to assemble at the cell surface. Over the past two decades, much of the research on LPS biogenesis has focused on the discovery and understanding of Lpt, a multi-protein complex that spans the cell envelope and functions to transport LPS from the inner membrane to the outer membrane. This paper focuses on the early steps of the transport of LPS by the Lpt machinery: the extraction of LPS from the inner membrane. The accompanying paper (May JM, Sherman DJ, Simpson BW, Ruiz N, Kahne D. 2015 Phil. Trans. R. Soc. B 370, 20150027. (doi:10.1098/rstb.2015.0027)) describes the subsequent steps as LPS travels through the periplasm and the outer membrane to its final destination at the cell surface. PMID- 26370942 TI - Outer membrane lipoprotein biogenesis: Lol is not the end. AB - Bacterial lipoproteins are lipid-anchored proteins that contain acyl groups covalently attached to the N-terminal cysteine residue of the mature protein. Lipoproteins are synthesized in precursor form with an N-terminal signal sequence (SS) that targets translocation across the cytoplasmic or inner membrane (IM). Lipid modification and SS processing take place at the periplasmic face of the IM. Outer membrane (OM) lipoproteins take the localization of lipoproteins (Lol) export pathway, which ends with the insertion of the N-terminal lipid moiety into the inner leaflet of the OM. For many lipoproteins, the biogenesis pathway ends here. We provide examples of lipoproteins that adopt complex topologies in the OM that include transmembrane and surface-exposed domains. Biogenesis of such lipoproteins requires additional steps beyond the Lol pathway. In at least one case, lipoprotein sequences reach the cell surface by being threaded through the lumen of a beta-barrel protein in an assembly reaction that requires the heteropentomeric Bam complex. The inability to predict surface exposure reinforces the importance of experimental verification of lipoprotein topology and we will discuss some of the methods used to study OM protein topology. PMID- 26370944 TI - The microbiome, HLA, and the pathogenesis of uveitis. AB - An understanding of the microbiome is emerging as an exciting and novel way to elucidate the regulation of the immune system. Since the immune system plays a major role in the pathogenesis of many diseases including most forms of uveitis, it is critical to clarify the relationship between our immune system and the commensal bacteria that coexist in every human being. PMID- 26370943 TI - Activities and regulation of peptidoglycan synthases. AB - Peptidoglycan (PG) is an essential component in the cell wall of nearly all bacteria, forming a continuous, mesh-like structure, called the sacculus, around the cytoplasmic membrane to protect the cell from bursting by its turgor. Although PG synthases, the penicillin-binding proteins (PBPs), have been studied for 70 years, useful in vitro assays for measuring their activities were established only recently, and these provided the first insights into the regulation of these enzymes. Here, we review the current knowledge on the glycosyltransferase and transpeptidase activities of PG synthases. We provide new data showing that the bifunctional PBP1A and PBP1B from Escherichia coli are active upon reconstitution into the membrane environment of proteoliposomes, and that these enzymes also exhibit DD-carboxypeptidase activity in certain conditions. Both novel features are relevant for their functioning within the cell. We also review recent data on the impact of protein-protein interactions and other factors on the activities of PBPs. As an example, we demonstrate a synergistic effect of multiple protein-protein interactions on the glycosyltransferase activity of PBP1B, by its cognate lipoprotein activator LpoB and the essential cell division protein FtsN. PMID- 26370945 TI - Endovascular mechanical recanalization of acute ischaemic stroke in octogenarians. AB - BACKGROUND: Multiple studies have shown a clinical benefit of thrombectomy in acute ischaemic stroke, but most of them excluded octogenarians. The purpose of this study was to compare the outcomes between octogenarians and younger patients after thrombectomy. MATERIALS AND METHODS: One hundred and sixty-six patients with large cerebral artery occlusion and consecutive thrombectomy were evaluated and divided into two patient age groups: younger than 80 years and older than 80 years. We compared recanalization rates, complications experienced, disability, death after discharge and at a 90-day follow-up between these age groups. RESULTS: Sixty-eight percent of octogenarians and 72 % of younger patients were registered with successful recanalization (p = 1.0). There was no significant difference in symptomatic intracerebral haemorrhage between the groups (p = 0.32). However, octogenarians had a significantly lower rate of good clinical outcome (24 % vs. 48 %; p = 0.008) and a higher mortality rate (36 % vs. 12 %; p = 0.0013). CONCLUSION: Octogenarians have a lower chance of good clinical outcome and a higher mortality rate despite successful recanalization. Nevertheless, 24 % of octogenarians were documented with mRS <=2. As this age group of octogenarians will grow prospectively, careful patient selection should be mandatory when considering octogenarians for thrombectomy. KEY POINTS: * Careful patient selection for thrombectomy should be mandatory in octogenarians. * Octogenarians have a higher mortality rate despite successful recanalization. * Nearly one third of octogenarians were documented with a good clinical outcome. PMID- 26370947 TI - Multiple Systems for the Motivational Control of Behavior and Associated Neural Substrates in Humans. AB - In this chapter, we will review evidence about the role of multiple distinct systems in driving the motivation to perform actions in humans. Specifically, we will consider the contribution of goal-directed action selection mechanisms, habitual action selection mechanisms and the influence of Pavlovian predictors on instrumental action selection. We will further evaluate evidence for the contribution of multiple brain areas including ventral frontal and dorsal cortical areas and several distinct parts of the striatum in these processes. Furthermore, we will consider circumstances in which adverse interactions between these systems can result in the decoupling of motivation from incentive valuation and performance. PMID- 26370948 TI - Synthesis, Biological Evaluation and Molecular Docking Studies of Piperidinylpiperidines and Spirochromanones Possessing Quinoline Moieties as Acetyl-CoA Carboxylase Inhibitors. AB - Acetyl-coenzyme A carboxylases (ACCs) play critical roles in the regulation of fatty acid metabolism and have been targeted for the development of drugs against obesity, diabetes and other metabolic diseases. Two series of compounds possessing quinoline moieties were designed, synthesized and evaluated for their potential to inhibit acetyl-CoA carboxylases. Most compounds showed moderate to good ACC inhibitory activities and compound 7a possessed the most potent biological activities against ACC1 and ACC2, with IC50 values of 189 nM and 172 nM, respectively, comparable to the positive control. Docking simulation was performed to position compound 7a into the active site of ACC to determine a probable binding model. PMID- 26370946 TI - Motivational Deficits in Schizophrenia and the Representation of Expected Value. AB - Motivational deficits (avolition and anhedonia) have historically been considered important negative symptoms of schizophrenia (SZ). Numerous studies have attempted to identify the neural substrates of avolition and anhedonia in schizophrenia , but these studies have not produced much agreement. Deficits in various aspects of reinforcement processing have been observed in individuals with schizophrenia, but it is not exactly clear which of these deficits actually engender motivational impairments in SZ. The purpose of this chapter is to examine how various reinforcement-related behavioral and neural signals could contribute to motivational impairments in both schizophrenia and psychiatric illness, in general. In particular, we describe different aspects of the concept of expected value (EV), such as the distinction between the EV of stimuli and the expected value of actions, the acquisition of value versus the estimation of value, and the discounting of value as a consequence of time or effort required. We conclude that avolition and anhedonia in SZ are most commonly tied to aberrant signals for expected value, in the context of learning. We discuss implications for further research on the neural substrates of motivational impairments in psychiatric illness. PMID- 26370949 TI - The Biosynthetic Pathways of Tanshinones and Phenolic Acids in Salvia miltiorrhiza. AB - Secondary metabolites from plants play key roles in human medicine and chemical industries. Due to limited accumulation of secondary metabolites in plants and their important roles, characterization of key enzymes involved in biosynthetic pathway will enable metabolic engineering or synthetic biology to improve or produce the compounds in plants or microorganisms, which provides an alternative for production of these valuable compounds. Salvia miltiorrhiza, containing tanshinones and phenolic acids as its active compounds, has been widely used for the treatment of cardiovascular and cerebrovascular diseases. The biosynthetic analysis of secondary metabolites in S. miltiorrhiza has made great progress due to the successful genetic transformation system, simplified hairy roots system, and high-throughput sequencing. The cloned genes in S. miltiorrhiza had provided references for functional characterization of the post-modification steps involved in biosynthesis of tanshinones and phenolic acids, and further utilization of these steps in metabolic engineering. The strategies used in these studies could provide solid foundation for elucidation of biosynthetic pathways of diterpenoids and phenolic acids in other species. The present review systematically summarizes recent advances in biosynthetic pathway analysis of tanshinones and phenolic acids as well as synthetic biology and metabolic engineering applications of the rate-limiting genes involved in the secondary metabolism in S. miltiorrhiza. PMID- 26370950 TI - Novel Steroidal Glycosides from the Bulbs of Lilium pumilum. AB - Examination of the bulbs of Lilium pumilum (Liliaceae) led to the isolation of four novel steroidal glycosides (1-4) with a 2,3,4-trisubstituted beta-d glucopyranosyl unit. In 1 and 3, the alpha-L-arabinopyranosyl moiety is linked to C-3 of the inner trisubstituted beta-D-glucopyranosyl group and is present as an usual 4C1 conformation. In contrast, in 2 and 4, the alpha-L-arabinopyranosyl moiety, which is attached to C-4 of the inner trisubstituted beta-D glucopyranosyl group, is present as a 1C4 conformation. The structures of the new steroidal glycosides were determined based on the results of spectroscopic analyses, including two-dimensional (2D) NMR data and hydrolysis. PMID- 26370951 TI - Metabolomics-Based Screening of Biofilm-Inhibitory Compounds against Pseudomonas aeruginosa from Burdock Leaf. AB - Screening of anti-biofilm compounds from the burdock leaf based on metabolomics is reported here. The crystal violet assay indicated 34% ethanol elution fraction of burdock leaf could completely inhibit biofilm formation of Pseudomonas aeruginosa at 1 mg.mL(-1). Then, the chemical composition of burdock leaf fraction was analyzed by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) and 11 active compounds (chlorogenic acid, caffeic acid, p coumaric acid, quercetin, ursolic acid, rutin, cynarin, luteolin, crocin, benzoic acid, and Tenacissoside I) were identified. Lastly, UPLC-MS analysis was employed to obtain the metabolic fingerprints of burdock leaf fractions before and after inhibiting the biofilm of Pseudomonas aeruginosa. The metabolic fingerprints were transformed to data, analyzed with PLS-DA (partial least squares discriminant analysis) and the peaks whose area was significantly changed were found out. Thus, 81 compounds were screened as potential anti-biofilm ingredients. Among them, rutin, ursolic acid, caffeic acid, p-coumaric acid and quercetin were identified and confirmed as the main anti-biofilm compounds in burdock leaf. The study provided basic anti-biofilm profile data for the compounds in burdock leaf, as well as provided a convenient method for fast screening of anti-biofilm compounds from natural plants. PMID- 26370952 TI - Structure and Antibacterial Activity of Ambobactin, a New Telomycin-Like Cyclic Depsipeptide Antibiotic Produced by Streptomyces ambofaciens F3. AB - A new telomycin-like cyclic depsipeptide, ambobactin (1), was isolated from the metabolites of Streptomyces ambofaciens F3, an endophyte of Platycladus orientalis. Its structure was elucidated on the basis of extensive spectroscopic analysis and advanced Marfey's method. Ambobactin is structurally related with telomycin, except that the configuration of the 3-methyltryptophanes in their structures is different. It exhibited strong antibacterial activity against both Gram-positive and Gram-negative bacteria. Furthermore, this investigation revealed that S. ambofaciens F3 is a new producer of telomycin-like antibiotics. PMID- 26370953 TI - Escherichia coli ASKA Clone Library Harboring tRNA-Specific Adenosine Deaminase (tadA) Reveals Resistance towards Xanthorrhizol. AB - Xanthorrhizol is a potent antimicrobial compound isolated from the rhizome of Curcuma xanthorrhiza. However, the mechanism of xanthorrhizol action is unknown. To screen for probable target(s), we introduced the ASKA pooled-plasmid library into Escherichia coli W3110 imp4213 and enriched the library for resistant clones with increasing concentrations of xanthorrhizol. After three rounds of enrichment, we found nine genes that increased xanthorrhizol resistance. The resistant clones were able to grow in LB medium containing 256 ug/mL xanthorrhizol, representing a 16-fold increase in the minimum inhibitory concentration. Subsequent DNA sequence analysis revealed that overexpression of tadA, galU, fucU, ydeA, ydaC, soxS, nrdH, yiiD, and mltF genes conferred increased resistance towards xanthorrhizol. Among these nine genes, tadA is the only essential gene. tadA encodes a tRNA-specific adenosine deaminase. Overexpression of E. coli W3110 imp4213 (pCA24N-tadA) conferred resistance to xanthorrhizol up to 128 ug/mL. Moreover, overexpression of two tadA mutant enzymes (A143V and F149G) led to a twofold increase in the MIC. These results suggest that the targets of xanthorrhizol may include tadA, which has never before been explored as an antibiotic target. PMID- 26370954 TI - Dihydro-5,6-dehydrokavain (DDK) from Alpinia zerumbet: Its Isolation, Synthesis, and Characterization. AB - Dihydro-5,6-dehydrokavain (DDK) is the major and most promising component of the tropical plant Alpinia zerumbet (shell ginger), a species of the ginger family Zingiberaceae. Alpinia zerumbet is known for its human use as a traditional herbal medicine, food, and dietary supplement. With its alpha-lactone ring, DDK belongs to the large chemical group of kavalactones, which are also found in kava (Piper methysticum), another herbal medicine; DDK is characterized by a double bond linkage at positions 5,6 and the absence of a double-bond linkage at positions 7,8. This dissociates DDK from other kavalactones with their linkages at positions 7,8 and 5,6 that are both either completely saturated or unsaturated, or may have an unsaturated bond at the position 7,8 as well as a saturated bond at the position 5,6. DDK is easily identified and quantified by HPLC and GC. DDK contents in fresh leaves, stems and rhizomes range from 80 to 410 mg/g, requiring solvent extraction procedures to ensure high DDK yield. This is best achieved by hexane extraction from fresh rhizomes that were previously boiled in water, allowing DDK yields of up to 424 mg/g. Successful synthesis of DDK can be achieved by asymmetric pathways, whereas its simple chemical structure facilitates the synthesis of DDK derivatives by HCl hydrolysis. Thus, all synthesized products may be used for various commercial purposes, including the potential development of promising antiobesity pharmaceutical drugs, preparation of specific and safe dietary supplements, and use as effective natural herbicides or fungicides. PMID- 26370955 TI - Anti-Enterovirus 71 Agents of Natural Products. AB - This review, with 42 references, presents the fascinating area of anti enterovirus 71 natural products over the last three decades for the first time. It covers literature published from 2005-2015 and refers to compounds isolated from biogenic sources. In total, 58 naturally-occurring anti-EV71 compounds are recorded. PMID- 26370956 TI - Enzymatic Transesterification of Kraft Lignin with Long Acyl Chains in Ionic Liquids. AB - Valorization of lignin is essential for the economic viability of the biorefinery concept. For example, the enhancement of lignin hydrophobicity by chemical esterification is known to improve its miscibility in apolar polyolefin matrices, thereby helping the production of bio-based composites. To this end and due to its many reactive hydroxyl groups, lignin is a challenging macromolecular substrate for biocatalyzed esterification in non-conventional media. The present work describes for the first time the lipase-catalyzed transesterification of Kraft lignin in ionic liquids (ILs). Three lipases, three 1-butyl-3 methylimidazolium based ILs and ethyl oleate as long chain acyl donor were selected. Best results were obtained with a hydrophilic/hydrophobic binary IL system (1-butyl-3-methylimidazolium trifluoromethanesulfonate/1-butyl-3 methylimidazolium hexafluoro- phosphate, 1/1 v/v) and the immobilized lipase B from Candida antarctica (CALB) that afforded a promising transesterification yield (ca. 30%). Similar performances were achieved by using 1-butyl-3 methylimidazolium hexafluorophosphate as a coating agent for CALB rather than as a co-solvent in 1-butyl-3-methylimidazolium trifluoromethane-sulfonate thus limiting the use of hydrophobic IL. Structural characterization of lignin oleate was performed by spectroscopic studies (FTIR and 1H-NMR). The synthesized lignin oleate exhibited interesting thermal and textural properties, different from those of the original Kraft lignin. PMID- 26370957 TI - Different Roles of GRP78 on Cell Proliferation and Apoptosis in Cartilage Development. AB - Eukaryotic cells possess several mechanisms to adapt to endoplasmic reticulum (ER) stress and thereby survive. ER stress activates a set of signaling pathways collectively termed as the unfolded protein response (UPR). We previously reported that Bone morphogenetic protein 2 (BMP2) mediates mild ER stress and activates UPR signal molecules in chondrogenesis. The mammalian UPR protects the cell against the stress of misfolded proteins in the endoplasmic reticulum. Failure to adapt to ER stress causes the UPR to trigger apoptosis. Glucose regulated protein 78 (GRP78), as an important molecular chaperone in UPR signaling pathways, is responsible for binding to misfolded or unfolded protein during ER stress. However the influence on GRP78 in BMP2-induced chondrocyte differentiation has not yet been elucidated and the molecular mechanism underlyng these processes remain unexplored. Herein we demonstrate that overexpression of GRP78 enhanced cell proliferation in chondrocyte development with G1 phase advance, S phase increasing and G2-M phase transition. Furthermore, overexpression of GRP78 inhibited ER stress-mediated apoptosis and then reduced apoptosis in chondrogenesis induced by BMP2, as assayed by cleaved caspase3, caspase12, C/EBP homologous protein (CHOP/DDIT3/GADD153), p-JNK (phosphorylated c Jun N-terminal kinase) expression during the course of chondrocyte differentiation by Western blot. In addition, flow cytometry (FCM) assay, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling (TUNEL) assay and immune-histochemistry analysis also proved this result in vitro and in vivo. It was demonstrated that GRP78 knockdown via siRNA activated the ER stress-specific caspase cascade in developing chondrocyte tissue. Collectively, these findings reveal a novel critical role of GRP78 in regulating ER stress-mediated apoptosis in cartilage development and the molecular mechanisms involved. PMID- 26370958 TI - Effect of Hepatitis C Virus Genotype 1b Core and NS5A Mutations on Response to Peginterferon Plus Ribavirin Combination Therapy. AB - We examined whether hepatitis C virus (HCV) genotype 1b core- and NS5A-region mutations are associated with response to peginterferon alpha-2b plus ribavirin combination therapy. A total of 103 patients with high HCV genotype 1b viral loads (>= 100 KIU/mL) were treated with the combination therapy. Pretreatment mutations in the core region and interferon sensitivity determining region (ISDR) in the NS5A region were analyzed. In univariate analysis, arginine and leucine at positions 70 and 91 in the core region, defined as double wild (DW)-type, were associated with early virologic response (p = 0.002), sustained virologic response (SVR) (p = 0.004), and non-response (p = 0.005). Non-threonine at position 110 was associated with SVR (p = 0.004). Multivariate analysis showed the following pretreatment predictors of SVR: hemoglobin level >= 14 g/dL (odds ratio (OR) 6.2, p = 0.04); platelet count >= 14 * 104/mm3 (OR 5.2, p = 0.04); aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio < 0.9 (OR 6.17, p = 0.009); DW-type (OR 6.8, p = 0.02); non-threonine at position 110 (OR 14.5, p = 0.03); and >= 2 mutations in the ISDR (OR 12.3, p = 0.02). Patients with non-DW-type, non-threonine at position 110, and < 2 ISDR mutations showed significantly lower SVR rates than others (11/45 (24.4%) vs. 27/37 (73.0%), respectively; p < 0.001). SVR can be predicted through core and NS5A region mutations and host factors like hemoglobin, platelet count, and AST/ALT ratio in HCV genotype 1b-infected patients treated with peginterferon and ribavirin combination therapy. PMID- 26370959 TI - An Effective Antifreeze Protein Predictor with Ensemble Classifiers and Comprehensive Sequence Descriptors. AB - Antifreeze proteins (AFPs) play a pivotal role in the antifreeze effect of overwintering organisms. They have a wide range of applications in numerous fields, such as improving the production of crops and the quality of frozen foods. Accurate identification of AFPs may provide important clues to decipher the underlying mechanisms of AFPs in ice-binding and to facilitate the selection of the most appropriate AFPs for several applications. Based on an ensemble learning technique, this study proposes an AFP identification system called AFP Ensemble. In this system, random forest classifiers are trained by different training subsets and then aggregated into a consensus classifier by majority voting. The resulting predictor yields a sensitivity of 0.892, a specificity of 0.940, an accuracy of 0.938 and a balanced accuracy of 0.916 on an independent dataset, which are far better than the results obtained by previous methods. These results reveal that AFP-Ensemble is an effective and promising predictor for large-scale determination of AFPs. The detailed feature analysis in this study may give useful insights into the molecular mechanisms of AFP-ice interactions and provide guidance for the related experimental validation. A web server has been designed to implement the proposed method. PMID- 26370960 TI - Physiological Dynamics in Demyelinating Diseases: Unraveling Complex Relationships through Computer Modeling. AB - Despite intense research, few treatments are available for most neurological disorders. Demyelinating diseases are no exception. This is perhaps not surprising considering the multifactorial nature of these diseases, which involve complex interactions between immune system cells, glia and neurons. In the case of multiple sclerosis, for example, there is no unanimity among researchers about the cause or even which system or cell type could be ground zero. This situation precludes the development and strategic application of mechanism-based therapies. We will discuss how computational modeling applied to questions at different biological levels can help link together disparate observations and decipher complex mechanisms whose solutions are not amenable to simple reductionism. By making testable predictions and revealing critical gaps in existing knowledge, such models can help direct research and will provide a rigorous framework in which to integrate new data as they are collected. Nowadays, there is no shortage of data; the challenge is to make sense of it all. In that respect, computational modeling is an invaluable tool that could, ultimately, transform how we understand, diagnose, and treat demyelinating diseases. PMID- 26370961 TI - Introducing DInaMo: A Package for Calculating Protein Circular Dichroism Using Classical Electromagnetic Theory. AB - The dipole interaction model is a classical electromagnetic theory for calculating circular dichroism (CD) resulting from the pi-pi* transitions of amides. The theoretical model, pioneered by J. Applequist, is assembled into a package, DInaMo, written in Fortran allowing for treatment of proteins. DInaMo reads Protein Data Bank formatted files of structures generated by molecular mechanics or reconstructed secondary structures. Crystal structures cannot be used directly with DInaMo; they either need to be rebuilt with idealized bond angles and lengths, or they need to be energy minimized to adjust bond lengths and bond angles because it is common for crystal structure geometries to have slightly short bond lengths, and DInaMo is sensitive to this. DInaMo reduces all the amide chromophores to points with anisotropic polarizability and all nonchromophoric aliphatic atoms including hydrogens to points with isotropic polarizability; all other atoms are ignored. By determining the interactions among the chromophoric and nonchromophoric parts of the molecule using empirically derived polarizabilities, the rotational and dipole strengths are determined leading to the calculation of CD. Furthermore, ignoring hydrogens bound to methyl groups is initially explored and proves to be a good approximation. Theoretical calculations on 24 proteins agree with experiment showing bands with similar morphology and maxima. PMID- 26370962 TI - To Extinguish the Fire from Outside the Cell or to Shutdown the Gas Valve Inside? Novel Trends in Anti-Inflammatory Therapies. AB - Cytokines are the most important soluble mediators of inflammation. Rare pediatric diseases provided exemplar conditions to study the anti-inflammatory efficacy of new generation therapies (biologics/biopharmaceuticals) selectively targeting single cytokines. Monoclonal antibodies and recombinant proteins have revolutionized anti-inflammatory therapies in the last two decades, allowing the specific targeting of single cytokines. They are very effective in extinguishing inflammation from outside the cell, even with the risk of an excessive and prolonged immunosuppression. Small molecules can enter the cell and shutdown the valve of inflammation by directly targeting signal proteins involved in cytokine release or in response to cytokines. They are orally-administrable drugs whose dosage can be easily adjusted to obtain the desired anti-inflammatory effect. This could make these drugs more suitable for a wide range of diseases as stroke, gout, or neurological impairment, where inflammatory activation plays a pivotal role as trigger. Autoinflammatory diseases, which have previously put anti cytokine proteins in the limelight, can again provide a valuable model to measure the real potential of small inhibitors as anti-inflammatory agents. PMID- 26370963 TI - MicroRNAs in Salivary Exosome as Potential Biomarkers of Aging. AB - The aim of this study was to examine whether salivary exosomal miRNAs could be identified as aging biomarkers. Fifteen young healthy volunteers (median age, 21.0 years) and 13 old individuals (median age, 66.0 years) were recruited. Unstimulated whole saliva was collected, salivary exosomes were isolated, and total RNA was extracted. In a microarray, 242 miRNAs were commonly detected in these two mixed samples. Based on the cut-off values of 2- or 0.5-fold changes (FC) and regulatory power for aging process, six candidate miRNAs (miR-24-3p, miR 371a-5p, miR-3175, miR-3162-5p, miR-671-5p, and miR-4667-5p) were selected. After comparing each total RNA obtained by the 15 young and 13 old individuals to validate the FC values using quantitative real-time PCR, miR-24-3p was identified as a novel candidate aging biomarker. This pilot study suggested that salivary exosomal miRNAs could be identified as candidate aging biomarkers. To confirm whether miR-24-3p in salivary exosomes are suitable biomarkers of aging, further validation research is required. PMID- 26370964 TI - Gene Expression Variations of Red-White Skin Coloration in Common Carp (Cyprinus carpio). AB - Teleosts have more types of chromatophores than other vertebrates and the genetic basis for pigmentation is highly conserved among vertebrates. Therefore, teleosts are important models to study the mechanism of pigmentation. Although functional genes and genetic variations of pigmentation have been studied, the mechanisms of different skin coloration remains poorly understood. The koi strain of common carp has various colors and patterns, making it a good model for studying the genetic basis of pigmentation. We performed RNA-sequencing for red skin and white skin and identified 62 differentially expressed genes (DEGs). Most of them were validated with RT-qPCR. The up-regulated DEGs in red skin were enriched in Kupffer's vesicle development while the up-regulated DEGs in white skin were involved in cytoskeletal protein binding, sarcomere organization and glycogen phosphorylase activity. The distinct enriched activity might be associated with different structures and functions in erythrophores and iridophores. The DNA methylation levels of two selected DEGs inversely correlated with gene expression, indicating the participation of DNA methylation in the coloration. This expression characterization of red-white skin along with the accompanying transcriptome-wide expression data will be a useful resource for further studies of pigment cell biology. PMID- 26370965 TI - Development of Seven Microsatellite Markers Using Next Generation Sequencing for the Conservation on the Korean Population of Dorcus hopei (E. Saunders, 1854) (Coleoptera, Lucanidae). AB - We developed microsatellite markers for genetic structural analyses of Dorcus hopei, a stag beetle species, using next generation sequencing and polymerase chain reaction (PCR)-based genotyping for regional populations. A total of 407,070,351 base pairs of genomic DNA containing >4000 microsatellite loci except AT repeats were sequenced. From 76 loci selected for primer design, 27 were polymorphic. Of these 27 markers, 10 were tested on three regional populations: two Chinese (Shichuan and Guangxi) and one Korean (Wanju). Three markers were excluded due to inconsistent amplification, genotyping errors, and Hardy-Weinberg equilibrium (HWE). By multi-locus genotyping, the allele number, observed heterozygosity and polymorphism information content of seven microsatellite loci were ranged 2-10, 0.1333-1.0000, and 0.1228-0.8509, respectively. In an analysis on the genetic differentiation among regional populations including one Japanese population and one cross-breeding population, the individual colored bar-plots showed that both Chinese populations were closer to each other than to the Far East Asian populations. In Far East Asian populations, Wanju and Nirasaki populations could not be distinguished from each other because the frequency of genetic contents was very similar in some individuals of two populations. Moreover, the cross-breeding population contained all patterns of genetic contents shown in Chinese, Korean, and Japanese populations, compared with the genetic content frequency of each regional population. As a result, we examined whether the cross-breeding population might be a hybrid population, and might contain a possibility of interbreeding with Chinese populations in parental generations. Therefore, these markers will be useful for analyses of genetic diversity in populations, genetic relationships between regional populations, genetic structure analyses, and origin tests. PMID- 26370967 TI - Ile-1781-Leu and Asp-2078-Gly Mutations in ACCase Gene, Endow Cross-resistance to APP, CHD, and PPZ in Phalaris minor from Mexico. AB - Herbicides that inhibit acetyl coenzyme A carboxylase (ACCase) are commonly used in Mexico to control weedy grasses such as little seed canarygrass (Phalaris minor). These herbicides are classified into three major families (ariloxyphenoxypropionates (APP), cyclohexanodiones (CHD), and, recently, phenylpyrazolines (PPZ)). In this work, the resistance to ACCase (APP, CHD, and PPZ) inhibiting herbicides was studied in a biotype of Phalaris minor (P. minor) from Mexico, by carrying out bioassays at the whole-plant level and investigating the mechanism behind this resistance. Dose-response and ACCase in vitro activity assays showed cross-resistance to all ACCase herbicides used. There was no difference in the absorption, translocation, and metabolism of the (14)C-diclofop methyl between the R and S biotypes. The PCR generated CT domain fragments of ACCase from the R biotype and an S reference were sequenced and compared. The Ile 1781-Leu and Asp-2078-Gly point mutations were identified. These mutations could explain the loss of affinity for ACCase by the ACCase-inhibing herbicides. This is the first report showing that this substitution confers resistance to APP, CHD, and PPZ herbicides in P. minor from Mexico. The mutations have been described previously only in a few cases; however, this is the first study reporting on a pattern of cross-resistance with these mutations in P. minor. The findings could be useful for better management of resistant biotypes carrying similar mutations. PMID- 26370966 TI - New Anti-Nodal Monoclonal Antibodies Targeting the Nodal Pre-Helix Loop Involved in Cripto-1 Binding. AB - Nodal is a potent embryonic morphogen belonging to the TGF-beta superfamily. Typically, it also binds to the ALK4/ActRIIB receptor complex in the presence of the co-receptor Cripto-1. Nodal expression is physiologically restricted to embryonic tissues and human embryonic stem cells, is absent in normal cells but re-emerges in several human cancers, including melanoma, breast, and colon cancer. Our aim was to obtain mAbs able to recognize Nodal on a major CBR (Cripto Binding-Region) site and to block the Cripto-1-mediated signalling. To achieve this, antibodies were raised against hNodal(44-67) and mAbs generated by the hybridoma technology. We have selected one mAb, named 3D1, which strongly associates with full-length rhNodal (KD 1.4 nM) and recognizes the endogenous protein in a panel of human melanoma cell lines by western blot and FACS analyses. 3D1 inhibits the Nodal-Cripto-1 binding and blocks Smad2/3 phosphorylation. Data suggest that inhibition of the Nodal-Cripto-1 axis is a valid therapeutic approach against melanoma and 3D1 is a promising and interesting agent for blocking Nodal-Cripto mediated tumor development. These findings increase the interest for Nodal as both a diagnostic and prognostic marker and as a potential new target for therapeutic intervention. PMID- 26370968 TI - Can Clethra barbinervis Distinguish Nickel and Cobalt in Uptake and Translocation? AB - Clethra barbinervis Sieb. et Zucc. accumulates Nickel (Ni) and Cobalt (Co) at high concentrations., We hypothesized that C. barbinervis cannot distinguish between Ni and Co because of the similar chemical properties of these two elements. To confirm this hypothesis and understand the role of these elements in C. barbinervis, we conducted a hydroponic split-root experiment using Ni and Co solutions. We found that the bioconcentration factor (BCF; metal concentration of each tissue/metal concentrations of each treatment solution) of Ni and Co did not significantly differ in the roots, but the BCF for Co was higher than that for Ni in the leaves. The leaves of C. barbinervis accumulated Ni or Co at high concentrations. We also found the simultaneous accumulation of Ni and Co by the multiple heavy metal treatments (Ni and Co) at high concentrations similar to those for the single treatments (Ni or Co). Elevated sulfur concentrations occurred in the roots and leaves of Co-treated seedlings but not in Ni. This result indicates that S was related to Co accumulation in the leaves. These results suggest that C. barbinervis distinguishes between Ni and Co during transport and accumulation in the leaves but not during root uptake. PMID- 26370969 TI - Cisplatin Targeting of Bacterial Ribosomal RNA Hairpins. AB - Cisplatin is a clinically important chemotherapeutic agent known to target purine bases in nucleic acids. In addition to major deoxyribonucleic acid (DNA) intrastrand cross-links, cisplatin also forms stable adducts with many types of ribonucleic acid (RNA) including siRNA, spliceosomal RNAs, tRNA, and rRNA. All of these RNAs play vital roles in the cell, such as catalysis of protein synthesis by rRNA, and therefore serve as potential drug targets. This work focused on platination of two highly conserved RNA hairpins from E. coli ribosomes, namely pseudouridine-modified helix 69 from 23S rRNA and the 790 loop of helix 24 from 16S rRNA. RNase T1 probing, MALDI mass spectrometry, and dimethyl sulfate mapping revealed platination at GpG sites. Chemical probing results also showed platination-induced RNA structural changes. These findings reveal solvent and structural accessibility of sites within bacterial RNA secondary structures that are functionally significant and therefore viable targets for cisplatin as well as other classes of small molecules. Identifying target preferences at the nucleotide level, as well as determining cisplatin-induced RNA conformational changes, is important for the design of more potent drug molecules. Furthermore, the knowledge gained through studies of RNA-targeting by cisplatin is applicable to a broad range of organisms from bacteria to human. PMID- 26370970 TI - The Effects of Cadmium at Low Environmental Concentrations on THP-1 Macrophage Apoptosis. AB - Cadmium at environmental concentrations is a risk factor for many diseases, including cardiovascular and neurodegenerative diseases, in which macrophages play an important role. The aim of this study was to evaluate the effects of cadmium at low environmental (nanomolar) concentrations on apoptotic processes in THP-1(acute monocytic leukemia cells line)-derived macrophages, with special focus on mitochondrial events involved. Macrophages were incubated with various cadmium chloride (CdCl2) solutions for 48 h at final concentrations of 5 nM, 20 nM, 200 nM and 2 uM CdCl2. Cell viability was measured using flow cytometry. Flow cytometric measurement (annexin V/FITC (annexin V/fluorescein isothiocyanate) and PI (propidium iodide) double staining) was used to quantify the extent of apoptosis. Fluorescence and confocal microscopy were used for imaging of apoptosis process. Changes in mitochondrial membrane potential were monitored using cytofluorimetry after cell staining with JC-1(5,5',6,6'-tetrachloro 1,1',3,3'-tetraethylbenzimidazol-carbocyane iodide) probe. Mitochondrial ROS (reactive oxygen species) levels were measured cytofluorimetrically after incubation of cells with mitochondrial superoxide indicator (MitoSOX) red fluorescent marker. The mRNA expression of Bcl-2 and Bax was analysed with qRT PCR. Our study demonstrates that cadmium, even at low environmental concentrations, exerts mitochondrial toxicity in THP-1 macrophages. Forty-eight hour exposure to very low concentrations reduces cell viability and results in cell death by apoptosis and necrosis. The decrease in mitochondrial membrane potential, increased ROS production, increased Bax and decreased Bcl-2 mRNA expression are mitochondrial events involved in cadmium-induced apoptosis. PMID- 26370971 TI - Nutritive Evaluation of the Bambara Groundnut Ci12 Landrace [Vigna subterranea (L.) Verdc. (Fabaceae)] Produced in Cote d'Ivoire. AB - The nutritional evaluation of the Bambara groundnut Ci12 landrace (Vigna subterranea (L.) Verdc.) seeds produced in Cote d'Ivoire shows a 19% content of protein, containing all the essential amino acids with tryptophan as the limiting amino acid, a total dietary fiber level of 10%, with a low soluble fraction content, and a fat content of 1.4%, with a high proportion of total unsaturated fatty acids (61%) of which 36% were n-6 fatty acids. This legume contains phosphorus, as the major mineral, followed by magnesium and calcium, and trace elements (iron, copper and zinc). It is characterized by the same amount of alpha tocopherol and antioxidant capacity as common legumes. The high concentration of essential amino acids, n-6 fatty acids and minerals, mainly Fe, in the Ci12 landrace of Bambara groundnut indicates that this local legume has the potentiality to improve the nutritional status in Cote d'Ivoire and it could be regarded as a nutrient dense food. PMID- 26370972 TI - MicroRNA, Pm-miR-2305, Participates in Nacre Formation by Targeting Pearlin in Pearl Oyster Pinctada martensii. AB - MicroRNAs (miRNAs) are noncoding RNA molecules that function as negative regulators of target genes. In our previous research, 258 pm-miRNAs were identified in Pinctada martensii by Solexa deep sequencing. Pm-miR-2305 was one of the identified pm-miRNAs with a potential function in biomineralization. In the present study, the precursor of pm-miR-2305 was predicted with 96 bp, containing a characteristic hairpin structure. Stem-loop qRT-PCR analysis indicated that pm-miR-2305 was constitutively expressed in all the tissues (adductor muscle, gill, mantle, hepatopancreas, foot, and gonad) of P. martensii and was highly expressed in the foot. After the over-expression of pm-miR-2305 in the mantle by mimics injection into the muscle of P. martensii, nacre demonstrated disorderly growth, as detected by scanning electron microscopy. Dual luciferase reporter gene assay indicated that pm-miR-2305 mimics could significantly inhibit the luciferase activity of the reporter containing the 3'UTR of the pearlin gene. Western blot analysis demonstrated that the protein expression of pearlin was down-regulated in the mantle tissue after the over expression of pm-miR-2305. Therefore, our data showed that pm-miR-2305 participated in nacre formation by targeting pearlin in P. martensii. PMID- 26370973 TI - The Proteome Profiles of the Cerebellum of Juvenile, Adult and Aged Rats--An Ontogenetic Study. AB - In this study, we searched for proteins that change their expression in the cerebellum (Ce) of rats during ontogenesis. This study focuses on the question of whether specific proteins exist which are differentially expressed with regard to postnatal stages of development. A better characterization of the microenvironment and its development may result from these study findings. A differential two-dimensional polyacrylamide gel electrophoresis (2DE) and matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis of the samples revealed that the number of proteins of the functional classes differed depending on the developmental stages. Especially members of the functional classes of biosynthesis, regulatory proteins, chaperones and structural proteins show the highest differential expression within the analyzed stages of development. Therefore, members of these functional protein groups seem to be involved in the development and differentiation of the Ce within the analyzed development stages. In this study, changes in the expression of proteins in the Ce at different postnatal developmental stages (postnatal days (P) 7, 90, and 637) could be observed. At the same time, an identification of proteins which are involved in cell migration and differentiation was possible. Especially proteins involved in processes of the biosynthesis and regulation, the dynamic organization of the cytoskeleton as well as chaperones showed a high amount of differentially expressed proteins between the analyzed dates. PMID- 26370975 TI - First Trimester Urine and Serum Metabolomics for Prediction of Preeclampsia and Gestational Hypertension: A Prospective Screening Study. AB - Hypertensive disorders of pregnancy, including preeclampsia, are major contributors to maternal morbidity. The goal of this study was to evaluate the potential of metabolomics to predict preeclampsia and gestational hypertension from urine and serum samples in early pregnancy, and elucidate the metabolic changes related to the diseases. Metabolic profiles were obtained by nuclear magnetic resonance spectroscopy of serum and urine samples from 599 women at medium to high risk of preeclampsia (nulliparous or previous preeclampsia/gestational hypertension). Preeclampsia developed in 26 (4.3%) and gestational hypertension in 21 (3.5%) women. Multivariate analyses of the metabolic profiles were performed to establish prediction models for the hypertensive disorders individually and combined. Urinary metabolomic profiles predicted preeclampsia and gestational hypertension at 51.3% and 40% sensitivity, respectively, at 10% false positive rate, with hippurate as the most important metabolite for the prediction. Serum metabolomic profiles predicted preeclampsia and gestational hypertension at 15% and 33% sensitivity, respectively, with increased lipid levels and an atherogenic lipid profile as most important for the prediction. Combining maternal characteristics with the urinary hippurate/creatinine level improved the prediction rates of preeclampsia in a logistic regression model. The study indicates a potential future role of clinical importance for metabolomic analysis of urine in prediction of preeclampsia. PMID- 26370974 TI - The Role of Mitochondrial DNA in Mediating Alveolar Epithelial Cell Apoptosis and Pulmonary Fibrosis. AB - Convincing evidence has emerged demonstrating that impairment of mitochondrial function is critically important in regulating alveolar epithelial cell (AEC) programmed cell death (apoptosis) that may contribute to aging-related lung diseases, such as idiopathic pulmonary fibrosis (IPF) and asbestosis (pulmonary fibrosis following asbestos exposure). The mammalian mitochondrial DNA (mtDNA) encodes for 13 proteins, including several essential for oxidative phosphorylation. We review the evidence implicating that oxidative stress-induced mtDNA damage promotes AEC apoptosis and pulmonary fibrosis. We focus on the emerging role for AEC mtDNA damage repair by 8-oxoguanine DNA glycosylase (OGG1) and mitochondrial aconitase (ACO-2) in maintaining mtDNA integrity which is important in preventing AEC apoptosis and asbestos-induced pulmonary fibrosis in a murine model. We then review recent studies linking the sirtuin (SIRT) family members, especially SIRT3, to mitochondrial integrity and mtDNA damage repair and aging. We present a conceptual model of how SIRTs modulate reactive oxygen species (ROS)-driven mitochondrial metabolism that may be important for their tumor suppressor function. The emerging insights into the pathobiology underlying AEC mtDNA damage and apoptosis is suggesting novel therapeutic targets that may prove useful for the management of age-related diseases, including pulmonary fibrosis and lung cancer. PMID- 26370977 TI - Anthocyanin Absorption and Metabolism by Human Intestinal Caco-2 Cells--A Review. AB - Anthocyanins from different plant sources have been shown to possess health beneficial effects against a number of chronic diseases. To obtain any influence in a specific tissue or organ, these bioactive compounds must be bioavailable, i.e., effectively absorbed from the gut into the circulation and transferred to the appropriate location within the body while still maintaining their bioactivity. One of the key factors affecting the bioavailability of anthocyanins is their transport through the gut epithelium. The Caco-2 cell line, a human intestinal epithelial cell model derived from a colon carcinoma, has been proven to be a good alternative to animal studies for predicting intestinal absorption of anthocyanins. Studies investigating anthocyanin absorption by Caco-2 cells report very low absorption of these compounds. However, the bioavailability of anthocyanins may be underestimated since the metabolites formed in the course of digestion could be responsible for the health benefits associated with anthocyanins. In this review, we critically discuss recent findings reported on the anthocyanin absorption and metabolism by human intestinal Caco-2 cells. PMID- 26370976 TI - Polymorphisms in the LPL and CETP Genes and Haplotype in the ESR1 Gene Are Associated with Metabolic Syndrome in Women from Southwestern Mexico. AB - Metabolic syndrome (MetS) is a combination of metabolic disorders associated with an increased risk for cardiovascular disease (CVD). Studies in women reported associations between polymorphisms in ESR1, LPL and CETP genes and MetS. Our aim was to evaluate the association between variants in ESR1, LPL and CETP genes with MetS and its components. Four hundred and eighty women were analyzed, anthropometric features and biochemical profiles were evaluated, and genotyping was performed by real-time PCR. We found an association with elevated glucose levels (odds ratio (OR) = 2.9; p = 0.013) in carrying the AA genotype of rs1884051 in the ESR1 gene compared with the GG genotype, and the CC genotype of rs328 in the LPL gene was associated with MetS compared to the CG or GG genotype (OR = 2.8; p = 0.04). Moreover, the GA genotype of rs708272 in the CETP gene is associated with MetS compared to the GG or AA genotype (OR = 1.8; p = 0.006). In addition the ACTCCG haplotype in the ESR1 gene is associated with a decrease in the risk of MetS (OR = 0.02; p < 0.001). In conclusion, our results show the involvement of the variants of ESR1, LPL and CETP genes in metabolic events related to MetS or some of its features. PMID- 26370978 TI - Effects of Low Molecular Weight Yeast beta-Glucan on Antioxidant and Immunological Activities in Mice. AB - To evaluate the antioxidant and immune effects of low molecular yeast beta-glucan on mice, three sulfated glucans from Saccharomyces cerevisiae (sGSCs) with different molecular weight (MW) and degrees of sulfation (DS) were prepared. The structures of the sGSCs were analyzed through high performance liquid chromatography-gel permeation chromatography (HPLC-GPC) and Fourier transform infrared spectroscopy (FTIR). sGSC1, sGSC2, and sGSC3 had MW of 12.9, 16.5 and 19.2 kDa, respectively, and DS of 0.16, 0.24 and 0.27, respectively. In vitro and in vivo experiments were conducted to evaluate the antioxidant and immunological activities of the sGSCs. In vitro experiment, the reactive oxygen species (ROS) scavenging activities were determined. In vivo experiment, 50 male BALB/c mice were divided into five groups. The sGSC1, sGSC2 and sGSC3 treatment groups received the corresponding sGSCs at 50 mg/kg/day each. The GSC (glucans from Saccharomyces cerevisiae) treatment group received 50 mg/kg/day GSC. The normal control group received equal volume of physiological saline solution. All treatments were administered intragastrically for 14 day. Results showed that sGSC1, sGSC2 and sGSC3 can scavenge 1,1-diphenyl-2-picryl-hydrazyl (DPPH), superoxide, and hydroxyl radicals in vitro. The strength of the radical scavenging effects of the sGSCs was in the order of sGSC1 > sGSC2 > sGSC3. Oral administration of sGSC1 significantly improved serum catalase (CAT) and glutathione peroxidase (GSH-Px) activities and decreased malondialdehyde (MDA) level in mice. sGSC1 significantly improved the spleen and thymus indexes and the lymphocyte proliferation, effectively enhanced the percentage of CD4+ T cells, decreased the percentage of CD8+ T cells, and elevated the CD4+/CD8+ ratio. sGSC1 significantly promoted the secretion of IL-2 and IFN-gamma. These results indicate that sGSC1 with low MW and DS has better antioxidant and immunological activities than the other sGSCs, and sGSC1 could be used as a new antioxidant and immune-enhancing agent. PMID- 26370979 TI - Identification and Characterization of Reference Genes for Normalizing Expression Data from Red Swamp Crawfish Procambarus clarkii. AB - qRT-PCR is a widely used technique for rapid and accurate quantification of gene expression data. The use of reference genes for normalization of the expression levels is crucial for accuracy. Several studies have shown that there is no perfect reference gene that is appropriate for use in all experimental conditions, and research on suitable reference genes in red swamp crawfish (Procambarus clarkii) is particularly scarce. In this study, eight commonly used crustacean reference genes were chosen from P. clarkii transcriptome data and investigated as potential candidates for normalization of qRT-PCR data. Expression of these genes under different experimental conditions was examined by qRT-PCR, and the stability of their expression was evaluated using three commonly used statistical algorithms, geNorm, NormFinder and BestKeeper. A final comprehensive ranking determined that EIF and 18S were the optimal reference genes for expression data from different tissues, while TBP and EIF were optimal for expression data from different ovarian developmental stages. To our knowledge, this is the first systematic analysis of reference genes for normalization of qRT-PCR data in P. clarkii. These results will facilitate more accurate and reliable expression studies of this and other crustacean species. PMID- 26370980 TI - Physiological, Ultrastructural and Proteomic Responses in the Leaf of Maize Seedlings to Polyethylene Glycol-Stimulated Severe Water Deficiency. AB - After maize seedlings grown in full-strength Hoagland solution for 20 days were exposed to 20% polyethylene glycol (PEG)-stimulated water deficiency for two days, plant height, shoot fresh and dry weights, and pigment contents significantly decreased, whereas malondialdehyde (MDA) content greatly increased. Using transmission electron microscopy, we observed that chloroplasts of mesophyll cells in PEG-treated maize seedlings were swollen, with a disintegrating envelope and disrupted grana thylakoid lamellae. Using two dimensional gel electrophoresis (2-DE) method, we were able to identify 22 protein spots with significantly altered abundance in the leaves of treated seedlings in response to water deficiency, 16 of which were successfully identified. These protein species were functionally classified into signal transduction, stress defense, carbohydrate metabolism, protein metabolism, and unknown categories. The change in the abundance of the identified protein species may be closely related to the phenotypic and physiological changes due to PEG stimulated water deficiency. Most of the identified protein species were putatively located in chloroplasts, indicating that chloroplasts may be prone to damage by PEG stimulated-water deficiency in maize seedlings. Our results help clarify the molecular mechanisms of the responses of higher plants to severe water deficiency. PMID- 26370981 TI - Genetically Encoded Voltage Indicators in Circulation Research. AB - Membrane potentials display the cellular status of non-excitable cells and mediate communication between excitable cells via action potentials. The use of genetically encoded biosensors employing fluorescent proteins allows a non invasive biocompatible way to read out the membrane potential in cardiac myocytes and other cells of the circulation system. Although the approaches to design such biosensors date back to the time when the first fluorescent-protein based Forster Resonance Energy Transfer (FRET) sensors were constructed, it took 15 years before reliable sensors became readily available. Here, we review different developments of genetically encoded membrane potential sensors. Furthermore, it is shown how such sensors can be used in pharmacological screening applications as well as in circulation related basic biomedical research. Potentials and limitations will be discussed and perspectives of possible future developments will be provided. PMID- 26370982 TI - SOX2 Promotes the Epithelial to Mesenchymal Transition of Esophageal Squamous Cells by Modulating Slug Expression through the Activation of STAT3/HIF-alpha Signaling. AB - The transcription factor sex determining region (Y SRY)-box 2 (SOX2) is known to play a crucial role in the maintenance of self renewal or pluripotency of undifferentiated embryonic and neuronal stem cells. An elevated expression of SOX2 has been correlated with poor prognosis of esophageal squamous cell carcinoma (ESCC). We sought to investigate the mechanism(s) by which SOX2 modulates the ESCC metastasis. The SOX2 coding DNA sequence was inserted into pCMV vector and stably transfected in ESCC cells (Eca-109). The effect of SOX2 over expression was evaluated on cell migration, invasion and epithelial to mesenchymal transition (EMT). We also measured the expression of Slug to explore if this transcription factor is involved in SOX2-mediated regulation of cell migration/invasion and EMT. In addition, we determined the role of STAT3/HIF 1alpha to further probe the mechanism of SOX2-mediated metastasis via Slug. Our results demonstrated that SOX2 over expressing Eca-109 cells showed an enhanced cell migration/invasion. Moreover, these cells exhibited the EMT characteristics, that is, a significantly suppressed expression of the epithelial cells marker with a concomitant enhancement of those of the mesenchymal markers. An increased expression of Slug in SOX2 over expressing cells suggested the involvement of this transcription factor in SOX2-regulated metastasis. Whereas the expressions of STAT3/HIF-1alpha were found to be up-regulated in SOX2 expressing cells, blockade of these transcription factors resulted in the inhibition of Slug expression at both protein and mRNA levels. CONCLUSION: These results suggest that SOX2 promoted the metastasis of ESCC, at least in part, by modulating Slug expression through the activation of STAT3/HIF-1alpha signaling. PMID- 26370983 TI - A Novel Nanoprobe for Multimodal Imaging Is Effectively Incorporated into Human Melanoma Metastatic Cell Lines. AB - To facilitate efficient drug delivery to tumor tissue, several nanomaterials have been designed, with combined diagnostic and therapeutic properties. In this work, we carried out fundamental in vitro and in vivo experiments to assess the labeling efficacy of our novel theranostic nanoprobe, consisting of glycogen conjugated with a red fluorescent probe and gadolinium. Microscopy and resazurin viability assays were used to study cell labeling and cell viability in human metastatic melanoma cell lines. Fluorescence lifetime correlation spectroscopy (FLCS) was done to investigate nanoprobe stability. Magnetic resonance imaging (MRI) was performed to study T1 relaxivity in vitro, and contrast enhancement in a subcutaneous in vivo tumor model. Efficient cell labeling was demonstrated, while cell viability, cell migration, and cell growth was not affected. FLCS showed that the nanoprobe did not degrade in blood plasma. MRI demonstrated that down to 750 cells/MUL of labeled cells in agar phantoms could be detected. In vivo MRI showed that contrast enhancement in tumors was comparable between Omniscan contrast agent and the nanoprobe. In conclusion, we demonstrate for the first time that a non-toxic glycogen-based nanoprobe may effectively visualize tumor cells and tissue, and, in future experiments, we will investigate its therapeutic potential by conjugating therapeutic compounds to the nanoprobe. PMID- 26370984 TI - A New HPLC-MS Method for Measuring Maslinic Acid and Oleanolic Acid in HT29 and HepG2 Human Cancer Cells. AB - Maslinic acid (MA) and oleanolic acid (OA), the main triterpenic acids present in olive, have important properties for health and disease prevention. MA selectively inhibits cell proliferation of the HT29 human colon-cancer cell line by inducing selective apoptosis. For measuring the MA and OA concentration inside the cell and in the culture medium, a new HPLC-MS procedure has been developed. With this method, a determination of the amount of MA and OA incorporated into HT29 and HepG2 human cancer-cell lines incubated with different concentrations of MA corresponding to 50% growth inhibitory concentration (IC50), IC50/2, IC50/4, and IC50/8 has been made. The results demonstrate that this method is appropriate for determining the MA and OA concentration in different types of cultured cells and reveals the specific dynamics of entry of MA into HT29 and HepG2 cells. PMID- 26370985 TI - CrWSKP1, an SKP1-like Gene, Is Involved in the Self-Incompatibility Reaction of "Wuzishatangju" (Citrus reticulata Blanco). AB - Plant S-phase kinase-associated protein 1 (SKP1) genes play crucial roles in plant development and differentiation. However, the role of SKP1 in citrus is unclear. Herein, we described a novel SKP1-like gene, designated as CrWSKP1, from "Wuzishatangju" (Citrus reticulata Blanco). The cDNA sequence of CrWSKP1 is 779 base pairs (bp) and contains an open reading frame (ORF) of 477 bp. The genomic sequence of the CrWSKP1 gene is 1296 bp with two exons and one intron. CrWSKP1 has high identity with SKP1-like genes from other plant species within two conserved regions. Approximately 85% of pollen tubes of self-pollinated CrWSKP1 transgenic tobaccos became twisted at four days after self-pollination. Pollen tube numbers of self-pollinated CrWSKP1 transformants entering into ovules were significantly fewer than that of the control. Seed number of self-pollinated CrWSKP1 transformants was significantly reduced. These results suggested that the CrWSKP1 is involved in the self-incompatibility (SI) reaction of "Wuzishatangju". PMID- 26370987 TI - An Ensemble Method to Distinguish Bacteriophage Virion from Non-Virion Proteins Based on Protein Sequence Characteristics. AB - Bacteriophage virion proteins and non-virion proteins have distinct functions in biological processes, such as specificity determination for host bacteria, bacteriophage replication and transcription. Accurate identification of bacteriophage virion proteins from bacteriophage protein sequences is significant to understand the complex virulence mechanism in host bacteria and the influence of bacteriophages on the development of antibacterial drugs. In this study, an ensemble method for bacteriophage virion protein prediction from bacteriophage protein sequences is put forward with hybrid feature spaces incorporating CTD (composition, transition and distribution), bi-profile Bayes, PseAAC (pseudo amino acid composition) and PSSM (position-specific scoring matrix). When performing on the training dataset 10-fold cross-validation, the presented method achieves a satisfactory prediction result with a sensitivity of 0.870, a specificity of 0.830, an accuracy of 0.850 and Matthew's correlation coefficient (MCC) of 0.701, respectively. To evaluate the prediction performance objectively, an independent testing dataset is used to evaluate the proposed method. Encouragingly, our proposed method performs better than previous studies with a sensitivity of 0.853, a specificity of 0.815, an accuracy of 0.831 and MCC of 0.662 on the independent testing dataset. These results suggest that the proposed method can be a potential candidate for bacteriophage virion protein prediction, which may provide a useful tool to find novel antibacterial drugs and to understand the relationship between bacteriophage and host bacteria. For the convenience of the vast majority of experimental Int. J. Mol. Sci. 2015, 16,21735 scientists, a user-friendly and publicly-accessible web-server for the proposed ensemble method is established. PMID- 26370986 TI - The Three Bacterial Lines of Defense against Antimicrobial Agents. AB - Antimicrobial agents target a range of extra- and/or intracellular loci from cytoplasmic wall to membrane, intracellular enzymes and genetic materials. Meanwhile, many resistance mechanisms employed by bacteria to counter antimicrobial agents have been found and reported in the past decades. Based on their spatially distinct sites of action and distribution of location, antimicrobial resistance mechanisms of bacteria were categorized into three groups, coined the three lines of bacterial defense in this review. The first line of defense is biofilms, which can be formed by most bacteria to overcome the action of antimicrobial agents. In addition, some other bacteria employ the second line of defense, the cell wall, cell membrane, and encased efflux pumps. When antimicrobial agents permeate the first two lines of defense and finally reach the cytoplasm, many bacteria will make use of the third line of defense, including alterations of intracellular materials and gene regulation to protect themselves from harm by bactericides. The presented three lines of defense theory will help us to understand the bacterial resistance mechanisms against antimicrobial agents and design efficient strategies to overcome these resistances. PMID- 26370988 TI - A Novel Ligustrazine Derivative T-VA Prevents Neurotoxicity in Differentiated PC12 Cells and Protects the Brain against Ischemia Injury in MCAO Rats. AB - Broad-spectrum drugs appear to be more promising for the treatment of acute ischemic stroke. In our previous work, a new ligustrazine derivative (3,5,6 trimethylpyrazin-2-yl) methyl 3-methoxy-4-[(3,5,6-trimethylpyrazin-2 yl)methoxy]benzoate (T-VA) showed neuroprotective effect on injured PC12 cells (EC50 = 4.249 uM). In the current study, we show that this beneficial effect was due to the modulation of nuclear transcription factor-kappaB/p65 (NF-kappaB/p65) and cyclooxygenase-2 (COX-2) expressions. We also show that T-VA exhibited neuroprotective effect in a rat model of ischemic stroke with concomitant improvement of motor functions. We propose that the protective effect observed in vivo is owing to increased vascular endothelial growth factor (VEGF) expression, decreased oxidative stress, and up-regulation of Ca(2+)-Mg(2+) ATP enzyme activity. Altogether, our results warrant further studies on the utility of T-VA for the potential treatment of ischemic brain injuries, such as stroke. PMID- 26370989 TI - Tetramethylpyrazine Protects Retinal Capillary Endothelial Cells (TR-iBRB2) against IL-1beta-Induced Nitrative/Oxidative Stress. AB - Blood-retinal barrier (BRB) breakdown is one of the primary causes of diabetic retinopathy (DR). The pro-inflammatory factor interleukin-1beta (IL-1beta) was reported to be involved in the induction of BRB breakdown during the pathogenesis of DR. In the present study, we investigated the protective effect of tetramethylpyrazine (TMP), a major active component of the traditional herb Ligusticum chuanxiong, on IL-1beta-induced cell death of the rat retinal capillary endothelial TR-iBRB2 cells. Our results showed that IL-1beta-induced cell dysfunction in TR-iBRB2 cells via inducing nitrative/oxidative stress; however, such effect was attenuated with the pre-treatment of TMP. The cellular protective effect of TMP was likely to be mediated through the inhibition of inducible nitric oxide synthase (iNOS) expression and leukostasis as well as suppression of reactive oxygen species (ROS) generation, mitochondrial dysfunction and MAPKs activation. These findings significantly contribute to a better understanding of the protective effect of TMP in DR and form the basis of the therapeutic development of TMP in treating such disease in the future. PMID- 26370990 TI - Homozygous ALOXE3 Nonsense Variant Identified in a Patient with Non-Bullous Congenital Ichthyosiform Erythroderma Complicated by Superimposed Bullous Majocchi's Granuloma: The Consequences of Skin Barrier Dysfunction. AB - Non-bullous congenital ichthyosiform erythroderma (NBCIE) is a hereditary disorder of keratinization caused by pathogenic variants in genes encoding enzymes important to lipid processing and terminal keratinocyte differentiation. Impaired function of these enzymes can cause pathologic epidermal scaling, significantly reduced skin barrier function. In this study, we have performed a focused, genetic analysis of a probrand affected by NBCIE and extended this to his consanguineous parents. Targeted capture and next-generation sequencing was performed on NBCIE associated genes in the proband and his unaffected consanguineous parents. We identified a homozygous nonsense variant c.814C>T (p.Arg272*) in ALOXE3 (NM_001165960.1) in the proband and discovered that his parents are both heterozygous carriers of the variant. The clinical manifestations of the proband's skin were consistent with NBCIE, and detailed histopathological assessment revealed epidermal bulla formation and Majocchi's granuloma. Infection with Trichophyton rubrum was confirmed by culture. The patient responded to oral terbinafine antifungal treatment. Decreased skin barrier function, such as that caused by hereditary disorders of keratinization, can increase the risk of severe cutaneous fungal infections and the formation of Majocchi's granuloma and associated alopecia. Patients with NBCIE should be alerted to the possible predisposition for developing dermatophytoses and warrant close clinical follow-up. PMID- 26370991 TI - Isolation of Specific Genomic Regions and Identification of Their Associated Molecules by Engineered DNA-Binding Molecule-Mediated Chromatin Immunoprecipitation (enChIP) Using the CRISPR System and TAL Proteins. AB - Comprehensive understanding of genome functions requires identification of molecules (proteins, RNAs, genomic regions, etc.) bound to specific genomic regions of interest in vivo. To perform biochemical and molecular biological analysis of specific genomic regions, we developed engineered DNA-binding molecule-mediated chromatin immunoprecipitation (enChIP) to purify genomic regions of interest. In enChIP, specific genomic regions are tagged for biochemical purification using engineered DNA-binding molecules, such as transcription activator-like (TAL) proteins and a catalytically inactive form of the clustered regularly interspaced short palindromic repeats (CRISPR) system. enChIP is a comprehensive approach that emphasizes non-biased search using next generation sequencing (NGS), microarrays, mass spectrometry (MS), and other methods. Moreover, this approach is not restricted to cultured cell lines and can be easily extended to organisms. In this review, we discuss applications of enChIP to elucidating the molecular mechanisms underlying genome functions. PMID- 26370993 TI - Design and Realization of a Three Degrees of Freedom Displacement Measurement System Composed of Hall Sensors Based on Magnetic Field Fitting by an Elliptic Function. AB - This paper presents the design and realization of a three degrees of freedom (DOFs) displacement measurement system composed of Hall sensors, which is built for the XYthetaz displacement measurement of the short stroke stage of the reticle stage of lithography. The measurement system consists of three pairs of permanent magnets mounted on the same plane on the short stroke stage along the Y, Y, X directions, and three single axis Hall sensors correspondingly mounted on the frame of the reticle stage. The emphasis is placed on the decoupling and magnetic field fitting of the three DOFs measurement system. The model of the measurement system is illustrated, and the XY positions and thetaZ rotation of the short stroke stage can be obtained by decoupling the sensor outputs. A magnetic field fitting by an elliptic function-based compensation method is proposed. The practical field intensity of a permanent magnet at a certain plane height can be substituted for the output voltage of a Hall sensors, which can be expressed by the elliptic function through experimental data as the crucial issue to calculate the three DOFs displacement. Experimental results of the Hall sensor displacement measurement system are presented to validate the proposed three DOFs measurement system. PMID- 26370992 TI - Surface Properties of Squalene/Meibum Films and NMR Confirmation of Squalene in Tears. AB - Squalene (SQ) possesses a wide range of pharmacological activities (antioxidant, drug carrier, detoxifier, hydrating, emollient) that can be of benefit to the ocular surface. It can come in contact with human meibum (hMGS; the most abundant component of the tear film lipid layer) as an endogenous tear lipid or from exogenous sources as eyelid sebum or pharmaceuticals. The aims of this study were to determine (i) if SQ is in tear lipids and (ii) its influence on the surface properties of hMGS films. Heteronuclear single quantum correlation NMR confirmed 7 mol % SQ in Schirmer's strips extracts. The properties of SQ/hMGS pseudo-binary films at the air/water interface were studied with Langmuir surface balance, stress-relaxation dilatational rheology and Brewster angle microscopy. SQ does not possess surfactant properties. When mixed with hMGS squalene (i) localized over the layers' thinner regions and (ii) did not affect the film pressure at high compression. Therefore, tear SQ is unlikely to instigate dry eye, and SQ can be used as a safe and "inert" ingredient in formulations to protect against dry eye. The layering of SQ over the thinner film regions in addition to its pharmacological properties could contribute to the protection of the ocular surface. PMID- 26370994 TI - Aptameric Recognition-Modulated Electroactivity of Poly(4-Styrenesolfonic Acid) Doped Polyaniline Films for Single-Shot Detection of Tetrodotoxin. AB - The work being reported is the first electrochemical sensor for tetrodotoxin (TTX). It was developed on a glassy carbon electrodes (C) that was modified with poly(4-styrenesolfonic acid)-doped polyaniline film (PANI/PSSA). An amine-end functionalized TTX-binding aptamer, 5'-NH2-AAAAATTTCACACGGGTGCCTCGGCTGTCC-3' (NH2 Apt), was grafted via covalent glutaraldehyde (glu) cross-linking. The resulting aptasensor (C//PANI+/PSSA-glu-NH2-Apt) was interrogated by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) in sodium acetate buffer (NaOAc, pH 4.8) before and after 30 min incubation in standard TTX solutions. Both CV and EIS results confirmed that the binding of the analyte to the immobilized aptamer modulated the electrochemical properties of the sensor: particularly the charge transfer resistance (Rct) of the PANI+/PSSA film, which served as a signal reporter. Based on the Rct calibration curve of the TTX aptasensor, the values of the dynamic linear range (DLR), sensitivity and limit of detection (LOD) of the sensor were determined to be 0.23-1.07 ng.mL(-1) TTX, 134.88 +/- 11.42 Omega.ng.mL(-1) and 0.199 ng.mL(-1), respectively. Further studies are being planned to improve the DLR as well as to evaluate selectivity and matrix effects in real samples. PMID- 26370995 TI - Segmentation of White Blood Cells through Nucleus Mark Watershed Operations and Mean Shift Clustering. AB - This paper presents a novel method for segmentation of white blood cells (WBCs) in peripheral blood and bone marrow images under different lights through mean shift clustering, color space conversion and nucleus mark watershed operation (NMWO). The proposed method focuses on obtaining seed points. First, color space transformation and image enhancement techniques are used to obtain nucleus groups as inside seeds. Second, mean shift clustering, selection of the C channel component in the CMYK model, and illumination intensity adjustment are employed to acquire WBCs as outside seeds. Third, the seeds and NMWO are employed to precisely determine WBCs and solve the cell adhesion problem. Morphological operations are further used to improve segmentation accuracy. Experimental results demonstrate that the algorithm exhibits higher segmentation accuracy and robustness compared with traditional methods. PMID- 26370996 TI - Revisiting Gaussian Process Regression Modeling for Localization in Wireless Sensor Networks. AB - Signal strength-based positioning in wireless sensor networks is a key technology for seamless, ubiquitous localization, especially in areas where Global Navigation Satellite System (GNSS) signals propagate poorly. To enable wireless local area network (WLAN) location fingerprinting in larger areas while maintaining accuracy, methods to reduce the effort of radio map creation must be consolidated and automatized. Gaussian process regression has been applied to overcome this issue, also with auspicious results, but the fit of the model was never thoroughly assessed. Instead, most studies trained a readily available model, relying on the zero mean and squared exponential covariance function, without further scrutinization. This paper studies the Gaussian process regression model selection for WLAN fingerprinting in indoor and outdoor environments. We train several models for indoor/outdoor- and combined areas; we evaluate them quantitatively and compare them by means of adequate model measures, hence assessing the fit of these models directly. To illuminate the quality of the model fit, the residuals of the proposed model are investigated, as well. Comparative experiments on the positioning performance verify and conclude the model selection. In this way, we show that the standard model is not the most appropriate, discuss alternatives and present our best candidate. PMID- 26370997 TI - Energy-Efficient Integration of Continuous Context Sensing and Prediction into Smartwatches. AB - As the availability and use of wearables increases, they are becoming a promising platform for context sensing and context analysis. Smartwatches are a particularly interesting platform for this purpose, as they offer salient advantages, such as their proximity to the human body. However, they also have limitations associated with their small form factor, such as processing power and battery life, which makes it difficult to simply transfer smartphone-based context sensing and prediction models to smartwatches. In this paper, we introduce an energy-efficient, generic, integrated framework for continuous context sensing and prediction on smartwatches. Our work extends previous approaches for context sensing and prediction on wrist-mounted wearables that perform predictive analytics outside the device. We offer a generic sensing module and a novel energy-efficient, on-device prediction module that is based on a semantic abstraction approach to convert sensor data into meaningful information objects, similar to human perception of a behavior. Through six evaluations, we analyze the energy efficiency of our framework modules, identify the optimal file structure for data access and demonstrate an increase in accuracy of prediction through our semantic abstraction method. The proposed framework is hardware independent and can serve as a reference model for implementing context sensing and prediction on small wearable devices beyond smartwatches, such as body-mounted cameras. PMID- 26370998 TI - Affinity Propagation Clustering of Measurements for Multiple Extended Target Tracking. AB - More measurements are generated by the target per observation interval, when the target is detected by a high resolution sensor, or there are more measurement sources on the target surface. Such a target is referred to as an extended target. The probability hypothesis density filter is considered an efficient method for tracking multiple extended targets. However, the crucial problem of how to accurately and effectively partition the measurements of multiple extended targets remains unsolved. In this paper, affinity propagation clustering is introduced into measurement partitioning for extended target tracking, and the elliptical gating technique is used to remove the clutter measurements, which makes the affinity propagation clustering capable of partitioning the measurement in a densely cluttered environment with high accuracy. The Gaussian mixture probability hypothesis density filter is implemented for multiple extended target tracking. Numerical results are presented to demonstrate the performance of the proposed algorithm, which provides improved performance, while obviously reducing the computational complexity. PMID- 26370999 TI - High-Temperature Dielectric Properties of Aluminum Nitride Ceramic for Wireless Passive Sensing Applications. AB - The accurate characterization of the temperature-dependent permittivity of aluminum nitride (AlN) ceramic is quite critical to the application of wireless passive sensors for harsh environments. Since the change of the temperature dependent permittivity will vary the ceramic-based capacitance, which can be converted into the change of the resonant frequency, an LC resonator, based on AlN ceramic, is prepared by the thick film technology. The dielectric properties of AlN ceramic are measured by the wireless coupling method, and discussed within the temperature range of 12 degrees C (room temperature) to 600 degrees C. The results show that the extracted relative permittivity of ceramic at room temperature is 2.3% higher than the nominal value of 9, and increases from 9.21 to 10.79, and the quality factor Q is decreased from 29.77 at room temperature to 3.61 at 600 degrees C within the temperature range. PMID- 26371001 TI - Design and Application of a High Sensitivity Piezoresistive Pressure Sensor for Low Pressure Conditions. AB - In this paper, a pressure sensor for low pressure detection (0.5 kPa-40 kPa) is proposed. In one structure (No. 1), the silicon membrane is partly etched to form a crossed beam on its top for stress concentration. An aluminum layer is also deposited as part of the beam. Four piezoresistors are fabricated. Two are located at the two ends of the beam. The other two are located at the membrane periphery. Four piezoresistors connect into a Wheatstone bridge. To demonstrate the stress concentrate effect of this structure, two other structures were designed and fabricated. One is a flat membrane structure (No. 2), the other is a structure with the aluminum beam, but without etched silicon (No. 3). The measurement results of these three structures show that the No.1 structure has the highest sensitivity, which is about 3.8 times that of the No. 2 structure and 2.7 times that of the No. 3 structure. They also show that the residual stress in the beam has some backside effect on the sensor performance. PMID- 26371000 TI - Novel PCR Assays Complement Laser Biosensor-Based Method and Facilitate Listeria Species Detection from Food. AB - The goal of this study was to develop the Listeria species-specific PCR assays based on a house-keeping gene (lmo1634) encoding alcohol acetaldehyde dehydrogenase (Aad), previously designated as Listeria adhesion protein (LAP), and compare results with a label-free light scattering sensor, BARDOT (bacterial rapid detection using optical scattering technology). PCR primer sets targeting the lap genes from the species of Listeria sensu stricto were designed and tested with 47 Listeria and 8 non-Listeria strains. The resulting PCR primer sets detected either all species of Listeria sensu stricto or individual L. innocua, L. ivanovii and L. seeligeri, L. welshimeri, and L. marthii without producing any amplified products from other bacteria tested. The PCR assays with Listeria sensu stricto-specific primers also successfully detected all species of Listeria sensu stricto and/or Listeria innocua from mixed culture-inoculated food samples, and each bacterium in food was verified by using the light scattering sensor that generated unique scatter signature for each species of Listeria tested. The PCR assays based on the house-keeping gene aad (lap) can be used for detection of either all species of Listeria sensu stricto or certain individual Listeria species in a mixture from food with a detection limit of about 104 CFU/mL. PMID- 26371002 TI - A Simplified, Light Emitting Diode (LED) Based, Modular System to be Used for the Rapid Evaluation of Fruit and Vegetable Quality: Development and Validation on Dye Solutions. AB - NIR spectroscopy has proven to be one of the most efficient and ready to transfer tools to monitor product's quality. Portable VIS/NIR instruments are particularly versatile and suitable for field use to monitor the ripening process or quality parameters. The aim of this work is to develop and evaluate a new simplified optoelectronic system for potential measurements on fruit and vegetables directly in the field. The development, characterization and validation of an operative prototype is discussed. LED technology was chosen for the design, and spectral acquisition at four specific wavelengths (630, 690, 750 and 850 nm) was proposed. Nevertheless, attention was given to the modularity and versatility of the system. Indeed, the possibility to change the light sources module with other wavelengths allows one to adapt the use of the same device for different foreseeable applications and objectives, e.g., ripeness evaluation, detection of particular diseases and disorders, chemical and physical property prediction, shelf life analysis, as well as for different natures of products (berry, leaf or liquid). Validation tests on blue dye water solutions have shown the capability of the system of discriminating low levels of reflectance, with a repeatability characterized by a standard deviation proportional to the measured intensity and in general limited to 2%-4%. PMID- 26371003 TI - New Opportunities in Mid-Infrared Emission Control. AB - Tunable laser absorption spectroscopy (TLAS) has been well accepted as a preferred measurement technique for many industrial applications in recent years, especially for in situ applications. Previously, mainly near-infrared lasers have been used in TLAS sensors. The advent of compact mid-infrared light sources, like quantum cascade lasers and interband cascade lasers, has made it possible to detect gases with better sensitivity by utilizing fundamental absorption bands and to measure species that do not have any absorption lines in the near-infrared spectral region. This technological advancement has allowed developing new sensors for gases, such as nitric oxide and sulfur dioxide, for industrial applications. Detection limits of better than 1 ppm.m for nitric oxide and better than 10 ppm.m for sulfur dioxide are demonstrated in field experiments. PMID- 26371004 TI - Development of Ionic Liquid Modified Disposable Graphite Electrodes for Label Free Electrochemical Detection of DNA Hybridization Related to Microcystis spp. AB - In this present study, ionic liquid (1-butyl-3-methylimidazolium hexafluorophosphate (IL)) modified pencil graphite electrode (IL-PGEs) was developed for electrochemical monitoring of DNA hybridization related to Microcystis spp. (MYC). The characterization of IL-PGEs was performed using microscopic and electrochemical techniques. DNA hybridization related to MYC was then explored at the surface of IL-PGEs using differential pulse voltammetry (DPV) technique. After the experimental parameters were optimized, the sequence selective DNA hybridization related to MYC was performed in the case of hybridization between MYC probe and its complementary DNA target, noncomplementary (NC) or mismatched DNA sequence (MM), or and in the presence of mixture of DNA target: NC (1:1) and DNA target: MM (1:1). PMID- 26371005 TI - An Improved Method of Parameter Identification and Damage Detection in Beam Structures under Flexural Vibration Using Wavelet Multi-Resolution Analysis. AB - This paper reports on a two-step approach for optimally determining the location and severity of damage in beam structures under flexural vibration. The first step focuses on damage location detection. This is done by defining the damage index called relative wavelet packet entropy (RWPE). The damage severities of the model in terms of loss of stiffness are assessed in the second step using the inverse solution of equations of motion of a structural system in the wavelet domain. For this purpose, the connection coefficient of the scaling function to convert the equations of motion in the time domain into the wavelet domain is applied. Subsequently, the dominant components based on the relative energies of the wavelet packet transform (WPT) components of the acceleration responses are defined. To obtain the best estimation of the stiffness parameters of the model, the least squares error minimization is used iteratively over the dominant components. Then, the severity of the damage is evaluated by comparing the stiffness parameters of the identified model before and after the occurrence of damage. The numerical and experimental results demonstrate that the proposed method is robust and effective for the determination of damage location and accurate estimation of the loss in stiffness due to damage. PMID- 26371006 TI - A Wireless Optogenetic Headstage with Multichannel Electrophysiological Recording Capability. AB - We present a small and lightweight fully wireless optogenetic headstage capable of optical neural stimulation and electrophysiological recording. The headstage is suitable for conducting experiments with small transgenic rodents, and features two implantable fiber-coupled light-emitting diode (LED) and two electrophysiological recording channels. This system is powered by a small lithium-ion battery and is entirely built using low-cost commercial off-the-shelf components for better flexibility, reduced development time and lower cost. Light stimulation uses customizable stimulation patterns of varying frequency and duty cycle. The optical power that is sourced from the LED is delivered to target light-sensitive neurons using implantable optical fibers, which provide a measured optical power density of 70 mW/mm2 at the tip. The headstage is using a novel foldable rigid-flex printed circuit board design, which results into a lightweight and compact device. Recording experiments performed in the cerebral cortex of transgenic ChR2 mice under anesthetized conditions show that the proposed headstage can trigger neuronal activity using optical stimulation, while recording microvolt amplitude electrophysiological signals. PMID- 26371007 TI - A New Trans-Tympanic Microphone Approach for Fully Implantable Hearing Devices. AB - Fully implantable hearing devices (FIHDs) have been developed as a new technology to overcome the disadvantages of conventional acoustic hearing aids. The implantable microphones currently used in FIHDs, however, have difficulty achieving high sensitivity to environmental sounds, low sensitivity to body noise, and ease of implantation. In general, implantable microphones may be placed under the skin in the temporal bone region of the skull. In this situation, body noise picked up during mastication and touching can be significant, and the layer of skin and hair can both attenuate and distort sounds. The new approach presently proposed is a microphone implanted at the tympanic membrane. This method increases the microphone's sensitivity by utilizing the pinna's directionally dependent sound collection capabilities and the natural resonances of the ear canal. The sensitivity and insertion loss of this microphone were measured in human cadaveric specimens in the 0.1 to 16 kHz frequency range. In addition, the maximum stable gain due to feedback between the trans-tympanic microphone and a round-window-drive transducer, was measured. The results confirmed in situ high-performance capabilities of the proposed trans tympanic microphone. PMID- 26371008 TI - Geometric Parameters Estimation and Calibration in Cone-Beam Micro-CT. AB - The quality of Computed Tomography (CT) images crucially depends on the precise knowledge of the scanner geometry. Therefore, it is necessary to estimate and calibrate the misalignments before image acquisition. In this paper, a Two-Piece Ball (TPB) phantom is used to estimate a set of parameters that describe the geometry of a cone-beam CT system. Only multiple projections of the TPB phantom at one position are required, which can avoid the rotation errors when acquiring multi-angle projections. Also, a corresponding algorithm is derived. The performance of the method is evaluated through simulation and experimental data. The results demonstrated that the proposed method is valid and easy to implement. Furthermore, the experimental results from the Micro-CT system demonstrate the ability to reduce artifacts and improve image quality through geometric parameter calibration. PMID- 26371009 TI - Use of Cyclo-Oxygenase Inhibitors Is Not Associated with Clinical Relapse in Inflammatory Bowel Disease: A Case-Control Study. AB - Patients with inflammatory bowel disease (IBD) often have associated conditions, for which anti-inflammatory medication with cyclo-oxygenase (COX) inhibitors may be helpful. The current evidence is conflicting regarding the role of COX inhibitors in causing relapse in IBD. This case-control study examined the association between the use of COX inhibitors and relapse of IBD. Logistic regression was used to analyse the relationship between COX-inhibitors and IBD relapse. Overall COX inhibitor use (combined non-steroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 agents) had a negative association with relapse of IBD (adjusted OR 0.26, 95% CI 0.09-0.80). This negative association was confined to ulcerative colitis (UC) (adjusted OR = 0.06, 95% CI 0.01-0.50) and no association was found in Crohn's disease (CD) patients (adjusted OR 1.25, 95% CI 0.18-7.46). The significant negative association between UC relapse and medication use was also seen with non-specific NSAIDs. Selective COX-2 inhibitor use was rare but non-significantly more common in stable patients. There was no association between low-dose aspirin or paracetamol use and relapse of CD or UC. We conclude that COX-inhibitor use was not associated with an increased risk of relapse in UC or CD, and may be protective in UC. Where indicated, NSAIDs should not be withheld from IBD patients. PMID- 26371010 TI - Ecology of Anti-Biofilm Agents I: Antibiotics versus Bacteriophages. AB - Bacteriophages, the viruses that infect bacteria, have for decades been successfully used to combat antibiotic-resistant, chronic bacterial infections, many of which are likely biofilm associated. Antibiotics as anti-biofilm agents can, by contrast, be inefficacious against even genetically sensitive targets. Such deficiencies in usefulness may result from antibiotics, as naturally occurring compounds, not serving their producers, in nature, as stand-alone disruptors of mature biofilms. Anti-biofilm effectiveness by phages, by contrast, may result from a combination of inherent abilities to concentrate lytic antibacterial activity intracellularly via bacterial infection and extracellularly via localized population growth. Considered here is the anti biofilm activity of microorganisms, with a case presented for why, ecologically, bacteriophages can be more efficacious than traditional antibiotics as medically or environmentally applied biofilm-disrupting agents. Four criteria, it can be argued, generally must be met, in combination, for microorganisms to eradicate biofilms: (1) Furnishing of sufficiently effective antibacterial factors, (2) intimate interaction with biofilm bacteria over extended periods, (3) associated ability to concentrate antibacterial factors in or around targets, and, ultimately, (4) a means of physically disrupting or displacing target bacteria. In nature, lytic predators of bacteria likely can meet these criteria whereas antibiotic production, in and of itself, largely may not. PMID- 26371011 TI - Ecology of Anti-Biofilm Agents II: Bacteriophage Exploitation and Biocontrol of Biofilm Bacteria. AB - Bacteriophages are the viruses of bacteria. In the guise of phage therapy they have been used for decades to successfully treat what are probable biofilm containing chronic bacterial infections. More recently, phage treatment or biocontrol of biofilm bacteria has been brought back to the laboratory for more rigorous assessment as well as towards the use of phages to combat environmental biofilms, ones other than those directly associated with bacterial infections. Considered in a companion article is the inherent ecological utility of bacteriophages versus antibiotics as anti-biofilm agents. Discussed here is a model for phage ecological interaction with bacteria as they may occur across biofilm-containing ecosystems. Specifically, to the extent that individual bacterial types are not highly abundant within biofilm-containing environments, then phage exploitation of those bacteria may represent a "Feast-or-famine" existence in which infection of highly localized concentrations of phage sensitive bacteria alternate with treacherous searches by the resulting phage progeny virions for new concentrations of phage-sensitive bacteria to infect. An updated synopsis of the literature concerning laboratory testing of phage use to combat bacterial biofilms is then provided along with tips on how "Ecologically" such phage-mediated biofilm control can be modified to more reliably achieve anti biofilm efficacy. PMID- 26371013 TI - Echinochrome A Improves Exercise Capacity during Short-Term Endurance Training in Rats. AB - Echinochrome A (Echi A) improves mitochondrial function in the heart; however, its effects on skeletal muscle are still unclear. We hypothesized that Echi A administration during short-term exercise may improve exercise capacity. Twenty four male Sprague-Dawley rats were randomly divided into the following groups: control group (CG), Echi A-treated group (EG), aerobic exercise group (AG), and aerobic exercise treated with Echi A group (AEG) (n = 6 per group). Echi A was administered intra-peritoneally (0.1 mg/kg of Echi A in 300 uL phosphate-buffered saline) daily 30 min before each exercise training. The AG and AEG groups performed treadmill running (20 m/min, 60 min/day) five days/week for two weeks. The exercise capacity was significantly higher in the AG and AEG groups compared to other groups. Interestingly, the exercise capacity increased more effectively in the AEG group. The body weight in the EG tended to be slightly lower than that in the other groups. There were no significant changes in the plasma lipids among the groups. However, the gastrocnemius muscle mitochondria content was greater in the EG and AEG groups. These findings show that Echi A administration after short term endurance training enhances exercise capacity, which was associated with an increase in skeletal muscle mitochondrial content. PMID- 26371012 TI - A Phospholipid-Protein Complex from Antarctic Krill Reduced Plasma Homocysteine Levels and Increased Plasma Trimethylamine-N-Oxide (TMAO) and Carnitine Levels in Male Wistar Rats. AB - Seafood is assumed to be beneficial for cardiovascular health, mainly based on plasma lipid lowering and anti-inflammatory effects of n-3 polyunsaturated fatty acids. However, other plasma risk factors linked to cardiovascular disease are less studied. This study aimed to penetrate the effect of a phospholipid-protein complex (PPC) from Antarctic krill on one-carbon metabolism and production of trimethylamine-N-oxide (TMAO) in rats. Male Wistar rats were fed isoenergetic control, 6%, or 11% PPC diets for four weeks. Rats fed PPC had reduced total homocysteine plasma level and increased levels of choline, dimethylglycine and cysteine, whereas the plasma level of methionine was unchanged compared to control. PPC feeding increased the plasma level of TMAO, carnitine, its precursors trimethyllysine and gamma-butyrobetaine. There was a close correlation between plasma TMAO and carnitine, trimethyllysine, and gamma-butyrobetaine, but not between TMAO and choline. The present data suggest that PPC has a homocysteine lowering effect and is associated with altered plasma concentrations of metabolites related to one-carbon metabolism and B-vitamin status in rats. Moreover, the present study reveals a non-obligatory role of gut microbiota in the increased plasma TMAO level as it can be explained by the PPC's content of TMAO. The increased level of carnitine and carnitine precursors is interpreted to reflect increased carnitine biosynthesis. PMID- 26371014 TI - Sensitization Rates for Various Allergens in Children with Allergic Rhinitis in Qingdao, China. AB - The aim of this study was to determine the prevalence of sensitization to common allergens in children with allergic rhinitis (AR) living in Qingdao, China. We conducted a retrospective analysis for AR cases, who underwent skin prick tests (SPT) in Qingdao. A total of 2841 children with AR qualified for the inclusion criteria (Age 3-5 years: 1500 children; Age 6-12 years: 1341 children). The most common inhaled allergens to which the AR children were sensitive were Dermatophagoides pteronyssinus (69.3%), Dermatophagoides farinae (66.2%) and mould 1 (Penicillium notatum 38.9%); while the corresponding ingested allergens were mussel (39.2%), shrimp (36.3%) and carp (36.5%). The prevalence of sensitization to inhaled allergens and food allergens was higher in children >6 years of age as compared to that in children 3-5 years of age (all p < 0.05). Children >6 years old were more sensitive to dust mite as compared to children 3 5 years old (p < 0.05). Sensitization to dust mite was more common in males than in females (p = 0.05). In this study, Dermatophagoides pteronyssinus and Dermatophagoides farinae were the most common allergens causing AR in children in Qingdao, China. Older children with AR, particularly males, were found to be more sensitive to dust mite. PMID- 26371015 TI - Capturing the Interrelationship between Objectively Measured Physical Activity and Sedentary Behaviour in Children in the Context of Diverse Environmental Exposures. AB - Even though physical activity and sedentary behaviour are two distinct behaviours, their interdependent relationship needs to be studied in the same environment. This study examines the influence of urban design, neighbourhood built and social environment, and household and individual factors on the interdependent relationship between objectively measured physical activity and sedentary behaviour in children in the Canadian city of Saskatoon. Saskatoon's built environment was assessed by two validated observation tools. Neighbourhood socioeconomic variables were derived from 2006 Statistics Canada Census and 2010 G5 Census projections. A questionnaire was administered to 10-14 year old children to collect individual and household data, followed by accelerometry to collect physical activity and sedentary behaviour data. Multilevel logistic regression models were developed to understand the interrelationship between physical activity and sedentary behaviour in the context of diverse environmental exposures. A complex set of factors including denser built environment, positive peer relationships and consistent parental support influenced the interrelationship between physical activity and sedentary behaviour. In developing interventions to facilitate active living, it is not only imperative to delineate pathways through which diverse environmental exposures influence physical activity and sedentary behaviour, but also to account for the interrelationship between physical activity and sedentary behaviour. PMID- 26371016 TI - Indicators for Environment Health Risk Assessment in the Jiangsu Province of China. AB - According to the framework of "Pressure-State-Response", this study established an indicator system which can reflect comprehensive risk of environment and health for an area at large scale. This indicator system includes 17 specific indicators covering social and economic development, pollution emission intensity, air pollution exposure, population vulnerability, living standards, medical and public health, culture and education. A corresponding weight was given to each indicator through Analytical Hierarchy Process (AHP) method. Comprehensive risk assessment of the environment and health of 58 counties was conducted in the Jiangsu province, China, and the assessment result was divided into four types according to risk level. Higher-risk counties are all located in the economically developed southern region of Jiangsu province and relatively high-risk counties are located along the Yangtze River and Xuzhou County and its surrounding areas. The spatial distribution of relatively low-risk counties is dispersive, and lower-risk counties mainly located in the middle region where the economy is somewhat weaker in the province. The assessment results provide reasonable and scientific basis for Jiangsu province Government in formulating environment and health policy. Moreover, it also provides a method reference for the comprehensive risk assessment of environment and health within a large area (provinces, regions and countries). PMID- 26371017 TI - Infectious Diseases, Urbanization and Climate Change: Challenges in Future China. AB - China is one of the largest countries in the world with nearly 20% of the world's population. There have been significant improvements in economy, education and technology over the last three decades. Due to substantial investments from all levels of government, the public health system in China has been improved since the 2003 severe acute respiratory syndrome (SARS) outbreak. However, infectious diseases still remain a major population health issue and this may be exacerbated by rapid urbanization and unprecedented impacts of climate change. This commentary aims to explore China's current capacity to manage infectious diseases which impair population health. It discusses the existing disease surveillance system and underscores the critical importance of strengthening the system. It also explores how the growing migrant population, dramatic changes in the natural landscape following rapid urbanization, and changing climatic conditions can contribute to the emergence and re-emergence of infectious disease. Continuing research on infectious diseases, urbanization and climate change may inform the country's capacity to deal with emerging and re-emerging infectious diseases in the future. PMID- 26371018 TI - Mental and Physical Symptoms of Female Rural Workers: Relation between Household and Rural Work. AB - This study aimed to investigate the relations among mental disorders, physical discomfort, household work and farm work among women. We conducted a cross sectional study based on the administration of a structured questionnaire to 182 female farm workers. The data were analyzed by means of Poisson regression, where the significance level was set to 5%. Results indicated that 111 (61%) participants reported work-related mental disorders and physical discomfort was reported by 160 (87.9%). The participants with mental disorders and at least moderate levels of physical discomfort reported significantly higher levels of physical demand, time working (temporal demand), total effort and frustration with regard to farm work, in addition to significantly higher levels of frustration with regard to housework. Women with moderate or greater levels of both physical discomfort and frustration with farm work increased the chances of mental disorders. The results illustrate the complex challenge for health professionals in caring for women with mental disorders and physical discomforts related to their farm work, in the context of both the farm and domestic work demands these workers experience. PMID- 26371019 TI - The Use, Perceived Effectiveness and Safety of Herbal Galactagogues During Breastfeeding: A Qualitative Study. AB - The World Health Organization recommends breastfeeding as the normal infant feeding method and that infants being breastfed should be regarded as the control group or norm reference in all instances. There are many factors which could contribute to a new mother ceasing breastfeeding early, with the most commonly reported reason being perceived insufficient breast milk supply. The use of herbal galactagogues is increasingly common worldwide. Literature review identified a need for more research in the area of herbal galactagogue use during breastfeeding. Twenty in-depth semi-structured interviews were undertaken with breastfeeding women who used herbal galactagogues, to document use and explore their perceived effectiveness and safety of herbal galactagogues. Several indicators of breastfeeding adequacy were mentioned as participants described their experiences with the use of herbal galactagogues. Confidence and self empowerment emerged as an over-arching theme linked to positive experiences with the use of herbal galactagogues. Despite the lack of clinical trial data on the actual increase in measured volume of breast milk production, indicators of breastfeeding adequacy boosted participants' confidence levels and resulted in psychological benefits. This study highlighted the importance of considering the potential psychological benefits of using herbal galactagogues, and how this translates into breastfeeding adequacy. PMID- 26371020 TI - Depression, Anxiety and Symptoms of Stress among Hong Kong Nurses: A Cross sectional Study. AB - Recent epidemiological data suggests 13.3% of Hong Kong residents suffered from Common Mental Disorders, most frequently mixed anxiety and depressive disorder. This study examines the weighted prevalence and associated risk factors of depression, anxiety and stress among Hong Kong nurses. A total of 850 nurses were invited to participate in this cross-sectional study. Participants completed the Depression, Anxiety and Stress Scale 21 and multiple logistic regression was used to determine significant relationships between variables. Chronic past-year illness and poor self-perceived mental health were significant correlates of past week depression, anxiety and stress. It confirmed further positive correlations between depression and divorce, widowhood and separation, job dissatisfaction, disturbance with colleagues, low physical activity levels and sleep problems. Marital status; general medicine; sleep problems, and a lack of leisure significantly correlated with anxiety. Stress was significantly associated with younger age, clinical inexperience, past-year disturbance with colleagues, low physical activity, no leisure and drinking alcohol. Nurses were more depressed, anxious and stressed than the local general population, with over one-third of our respondents classified as subject to these disorders. PMID- 26371022 TI - An Examination of Two Policy Networks Involved in Advancing Smokefree Policy Initiatives. AB - This study examines smokefree policy networks in two cities-Kansas City and St. Louis, Missouri-one that was successful in achieving widespread policy success, and one that was not. Descriptive social network analyses and visual network mapping were used to compare importance and contact relationships among actors involved in the smokefree policy initiatives. In Kansas City, where policy adoption was achieved, there was a higher level of connectivity among members, with network members being in contact with an average of more than five people, compared to just over two people for the St. Louis network. For both cities, despite being recognized as important, politicians were in contact with the fewest number of people. Results highlight the critical need to actively engage a variety of stakeholders when attempting city wide public health policy change. As evident by the success in smokefree policy adoption throughout Kansas City compared to St. Louis, closer linkages and continued communication among stakeholders including the media, coalitions, public health agencies, policymakers, and other partners are essential if we are to advance and broaden the impact of public health policy. Results indicate that the presence of champions, or those that play leadership roles in actively promoting policy by linking individuals and organizations, play an important role in advancing public health policy. Those working in public health should examine their level of engagement with the policy process and implement strategies for improving that engagement through relationship building and ongoing interactions with a variety of stakeholders, including policymakers. PMID- 26371023 TI - What Do Breastfeeding Women Taking Herbal Galactagogues Perceive of Community Pharmacists' Role in Breastfeeding Support? A Qualitative Study. AB - Information from pharmacists may affect breastfeeding womens' decisions and choice of therapy. Community pharmacies remain one of the main sources of herbal medicines in Australia. In this study, we aimed to explore the perspectives of breastfeeding women on pharmacists' role and whether there is potential for role expansion, as well as the facilitators and barriers in meeting their healthcare related needs in the community pharmacy setting. Semi-structured in-depth interviews were conducted with 20 Western Australian women who were using one or more herbal galactagogues while breastfeeding. Participants' views were classified into three major themes: (i) facilitators and (ii) barriers to an increased role of pharmacists; and (iii) implementation of breastfeeding related services in community pharmacy settings. Overall perspectives of participants were positive about the potential for role expansion of pharmacists to meet their breastfeeding-related needs. Whilst most participants perceived community pharmacies as convenient sources of trusted information, some recognised barriers to an increased role of pharmacists. Several breastfeeding support services perceived to be useful in community pharmacy settings were identified. Issues raised highlighted areas of pharmacy practice which required improvement and revealed opportunities for expansion of pharmacists' role to better support women and promote breastfeeding in the community. PMID- 26371021 TI - Bisphenol-A and Female Infertility: A Possible Role of Gene-Environment Interactions. AB - BACKGROUND: Bisphenol-A (BPA) is widely used and ubiquitous in the environment. Animal studies indicate that BPA affects reproduction, however, the gene environment interaction mechanism(s) involved in this association remains unclear. We performed a literature review to summarize the evidence on this topic. METHODS: A comprehensive search was conducted in PubMed using as keywords BPA, gene, infertility and female reproduction. Full-text articles in both human and animals published in English prior to December 2014 were selected. RESULTS: Evidence shows that BPA can interfere with endocrine function of hypothalamic pituitary axis, such as by changing gonadotropin-releasing hormones (GnRH) secretion in hypothalamus and promoting pituitary proliferation. Such actions affect puberty, ovulation and may even result in infertility. Ovary, uterus and other reproductive organs are also targets of BPA. BPA exposure impairs the structure and functions of female reproductive system in different times of life cycle and may contribute to infertility. Both epidemiological and experimental evidences demonstrate that BPA affects reproduction-related gene expression and epigenetic modification that are closely associated with infertility. The detrimental effects on reproduction may be lifelong and transgenerational. CONCLUSIONS: Evidence on gene-environment interactions, especially from human studies, is still limited. Further research on this topic is warranted. PMID- 26371024 TI - "An Environment Built to Include Rather than Exclude Me": Creating Inclusive Environments for Human Well-Being. AB - Contemporary discourses which challenge the notion of health as the "absence of disease" are prompting changes in health policy and practice. People with disability have been influential in progressing our understanding of the impact of contextual factors in individual and population health, highlighting the impact of environmental factors on functioning and inclusion. The World Health Organization's (WHO) more holistic definition of health as "wellbeing" is now applied in frameworks and legislation, and has long been understood in occupational therapy theory. In practice, however, occupational therapists and other professionals often address only local and individual environmental factors to promote wellbeing, within systems and societies that limit equity in population health and restrict inclusion in communities. This paper presents an in-depth analysis of the supports and accommodations identified by a cohort of individuals (n-100) living with disability. A range of environmental facilitators and barriers were identified in peoples' experience of "inclusive community environs" and found to influence inclusion and wellbeing. The roles and responsibilities of individuals, professionals, and society to enact change in environments are discussed in light of these findings. Recommendations include a focus on the subjective experience of environments, and application of theory from human rights and inclusive economics to address the multiple dimensions and levels of environments in working towards inclusion and wellbeing. PMID- 26371025 TI - Quality of Drinking Water Treated at Point of Use in Residential Healthcare Facilities for the Elderly. AB - Municipal tap water is increasingly treated at the point of use (POU) to improve the acceptability and palatability of its taste. The aim of this study was to assess the bacteriologic and nutritional characteristics of tap water treated at the point of use in residential healthcare facilities for the elderly. Two types of POU devices were used: microfiltered water dispensers (MWDs) and reverse osmosis water dispensers (ROWDs). All samples of water entering the devices and leaving them were tested for the bacteriological parameters set by Italian regulations for drinking water and for opportunistic pathogens associated with various infections in healthcare settings; in addition, the degree of mineralization of the water was assessed. The results revealed widespread bacterial contamination in the POU treatment devices, particularly from potentially pathogenic species. As expected, the use of ROWDs led to a decrease in the saline content of the water. In conclusion, the use of POU treatment in healthcare facilities for the elderly can be considered advisable only if the devices are constantly and carefully maintained. PMID- 26371026 TI - High Birth Weight Increases the Risk for Bone Tumor: A Systematic Review and Meta Analysis. AB - There have been several epidemiologic studies on the relationship between high birth weight and the risk for bone tumor in the past decades. However, due to the rarity of bone tumors, the sample size of individual studies was generally too small for reliable conclusions. Therefore, we have performed a meta-analysis to pool all published data on electronic databases with the purpose to clarify the potential relationship. According to the inclusion and exclusion criteria, 18 independent studies with more than 2796 cases were included. As a result, high birth weight was found to increase the risk for bone tumor with an Odds Ratio (OR) of 1.13, with the 95% confidence interval (95% CI) ranging from 1.01 to 1.27. The OR of bone tumor for an increase of 500 gram of birth weight was 1.01 (95% CI 1.00-1.02; p = 0.048 for linear trend). Interestingly, individuals with high birth weight had a greater risk for osteosarcoma (OR = 1.22, 95% CI 1.06 1.40, p = 0.006) than those with normal birth weight. In addition, in the subgroup analysis by geographical region, elevated risk was detected among Europeans (OR = 1.14, 95% CI 1.00-1.29, p = 0.049). The present meta-analysis supported a positive association between high birth weight and bone tumor risk. PMID- 26371027 TI - Effect of Sodium Selenite on Pathological Changes and Renal Functions in Broilers Fed a Diet Containing Aflatoxin B1. AB - To evaluate the renal toxicity of dietary aflatoxin B1 (AFB1) and ameliorating effects of added dietary sodium selenite in broiler, renal histopathological changes, ultrastructural changes, and renal function parameters were monitored at 7, 14, and 21 days of age. Two hundred one-day-old healthy male Avian broilers were divided into four groups, namely control group, AFB1 group (0.3 mg/kg AFB1), +Se group (0.4 mg/kg Se), and AFB1+Se group (0.3 mg/kg AFB1+0.4 mg/kg Se). Compared with that of the control group, the relative weight of kidney was increased in the AFB1 group. There were no significant differences between the AFB1+Se group and the control group. By histopathological observation, the renal epithelia were swelling and necrosis at 7 and 21 days of age. Ultrastructurally, the lipid droplets and expanded endoplasmic reticulum appeared in the plasma of epithelia cells in the AFB1 group. Enlarged mitochondria with degenerated cristae were observed in the +Se group. Compared with the control group, the contents of serum creatinine and serum uric acid in the AFB1 group were increased, while the activity of renal Na+-K+ ATPase was decreased. When 0.4 mg/kg selenium was added into the diet containing 0.3 mg/kg AFB1, there were no obvious histological changes in the AFB1+Se group, and the contents of the serum creatinine and serum uric acid contents and the activity of renal Na+-K+ ATPase were close to those in the control group. In conclusion, sodium selenite exhibited protective effects on AFB1-induced kidney toxicity in broilers. PMID- 26371028 TI - Pollution Prevention through Peer Education: A Community Health Worker and Small and Home-Based Business Initiative on the Arizona-Sonora Border. AB - Government-led pollution prevention programs tend to focus on large businesses due to their potential to pollute larger quantities, therefore leaving a gap in programs targeting small and home-based businesses. In light of this gap, we set out to determine if a voluntary, peer education approach led by female, Hispanic community health workers (promotoras) can influence small and home-based businesses to implement pollution prevention strategies on-site. This paper describes a partnership between promotoras from a non-profit organization and researchers from a university working together to reach these businesses in a predominately Hispanic area of Tucson, Arizona. From 2008 to 2011, the promotora led pollution prevention program reached a total of 640 small and home-based businesses. Program activities include technical trainings for promotoras and businesses, generation of culturally and language appropriate educational materials, and face-to-face peer education via multiple on-site visits. To determine the overall effectiveness of the program, surveys were used to measure best practices implemented on-site, perceptions towards pollution prevention, and overall satisfaction with the industry-specific trainings. This paper demonstrates that promotoras can promote the implementation of pollution prevention best practices by Hispanic small and home-based businesses considered "hard-to-reach" by government-led programs. PMID- 26371029 TI - Drug-Induced Nephrotoxicity and Dose Adjustment Recommendations: Agreement Among Four Drug Information Sources. AB - : Hospitalized patients require the use of a variety of drugs, many of which individually or in combination have the potential to cause kidney damage. The use of potentially nephrotoxic drugs is often unavoidable, and the need for dose adjustment should be evaluated. This study is aimed at assessing concordance in information on drug-induced nephrotoxicity and dose adjustment recommendations by comparing four drug information sources (DRUGDEX((r)), UpToDate((r)), Medscape((r)) and the Brazilian Therapeutic Formulary) using the formulary of a Brazilian public hospital. A total of 218 drugs were investigated. The global Fleiss' kappa coefficient was 0.265 for nephrotoxicity (p < 0.001; CI 95%, 0.211 0.319) and 0.346 for recommendations (p < 0.001; CI 95%, 0.292-0.401), indicating fair concordance among the sources. Anti-infectives and anti-hypertensives were the main drugs cited as nephrotoxic by the different sources. There were no clear definitions for qualitative data or quantitative values for dose adjustments among the four information sources. There was no advice for dosing for a large number of the drugs in the international databases. The National Therapeutic Formulary offered imprecise dose adjustment recommendations for many nephrotoxic drugs. Discrepancies among information sources may have a clinical impact on patient care and contribute to drug-related morbidity and mortality. PMID- 26371030 TI - Topical Anti-Nuclear Factor-Kappa B Small Interfering RNA with Functional Peptides Containing Sericin-Based Hydrogel for Atopic Dermatitis. AB - The small interfering RNA (siRNA) is suggested to offer a novel means of treating atopic dermatitis (AD) because it allows the specific silencing of genes related to AD pathogenesis. In our previous study, we found that siRNA targeted against RelA, an important nuclear factor-kappa B (NF-kappaB) subdomain, with functional peptides, showed therapeutic effects in a mouse model of AD. In the present study, to develop a topical skin application against AD, we prepared a hydrogel containing anti-RelA siRNA and functional peptides and determined the intradermal permeation and the anti-AD effects in an AD mouse model. We selected the silk protein, sericin (SC), which is a versatile biocompatible biomaterial to prepare hydrogel as an aqueous gel base. We found that the siRNA was more widely delivered to the site of application in AD-induced ear skin of mice after topical application via the hydrogel containing functional peptides than via the preparation without functional peptides. In addition, the ear thickness and clinical skin severity of the AD-induced mice treated with hydrogel containing anti-RelA siRNA with functional peptides improved more than that of mice treated with the preparation formulated with negative siRNA. PMID- 26371031 TI - Effect of Crosslinking Agent Concentration on the Properties of Unmedicated Hydrogels. AB - Novel polyethylene oxide (PEO) hydrogel films were synthesized via UV crosslinking with varying concentrations of pentaerythritol tetra-acrylate (PETRA) as crosslinking agent. The aim was to study the effects of the crosslinking agent on the material properties of hydrogel films intended for dermatological applications. Fabricated film samples were characterized using swelling studies, scanning electron microscopy, tensile testing and rheometry. Films showed rapid swelling and high elasticity. The increase of PETRA concentration resulted in significant increase in the gel fraction and crosslinking density (rhoc), while causing a significant decrease in the equilibrium water content (EWC), average molecular weight between crosslinks (?({?overline{M}}_{c}?)), and mesh size (zeta) of films. From the scanning electron microscopy, cross-linked PEO hydrogel network appeared as cross-linked mesh-like structure with interconnected micropores. Rheological studies showed PEO films required a minimum of 2.5% w/w PETRA to form stable viscoelastic solid gels. Preliminary studies concluded that a minimum of 2.5% w/w PETRA is required to yield films with desirable properties for skin application. PMID- 26371032 TI - Per-Arnt-Sim Kinase (PASK): An Emerging Regulator of Mammalian Glucose and Lipid Metabolism. AB - Per-Arnt-Sim Kinase (PASK) is an evolutionarily-conserved nutrient-responsive protein kinase that regulates lipid and glucose metabolism, mitochondrial respiration, phosphorylation, and gene expression. Recent data suggests that mammalian PAS kinase is involved in glucose metabolism and acts on pancreatic islet alpha/beta cells and glycogen synthase (GS), affecting insulin secretion and blood glucose levels. In addition, PASK knockout mice (PASK-/-) are protected from obesity, liver triglyceride accumulation, and insulin resistance when fed a high-fat diet, implying that PASK may be a new target for metabolic syndrome (MetS) treatment as well as the cellular nutrients and energy sensors-adenosine monophosphate (AMP)-activated protein kinase (AMPK) and the targets of rapamycin (m-TOR). In this review, we will briefly summarize the regulation of PASK on mammalian glucose and lipid metabolism and its possible mechanism, and further explore the potential targets for MetS therapy. PMID- 26371033 TI - Potential Bio-Control Agent from Rhodomyrtus tomentosa against Listeria monocytogenes. AB - Listeria monocytogenes is an important foodborne pathogen implicated in many outbreaks of listeriosis. This study aimed at screening for the potential use of Rhodomyrtus tomentosa ethanolic leaf extract as a bio-control agent against L. monocytogenes. Twenty-two L. monocytogenes isolates were checked with 16 commercial antibiotics and isolates displayed resistance to 10 antibiotics. All the tested isolates were sensitive to the extract with inhibition zones ranging from 14 to 16 mm. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values ranged from 16 to 32 ug/mL and 128 to 512 ug/mL, respectively. Time-kill assay showed that the extract had remarkable bactericidal effects on L. monocytogenes. The extract at a concentration of 16 ug/mL reduced tolerance to 10% NaCl in L. monocytogenes in 4 h. Stationary phase L. monocytogenes cells were rapidly inactivated by greater than 3-log units within 30 min of contact time with R. tomentosa extract at 128 ug/mL. Electron microscopy revealed fragmentary bacteria with changes in the physical and morphological properties. Our study demonstrates the potential of the extract for further development into a bio-control agent in food to prevent the incidence of L. monocytogenes contamination. PMID- 26371034 TI - Additional Value of CH4 Measurement in a Combined (13)C/H2 Lactose Malabsorption Breath Test: A Retrospective Analysis. AB - The lactose hydrogen breath test is a commonly used, non-invasive method for the detection of lactose malabsorption and is based on an abnormal increase in breath hydrogen (H2) excretion after an oral dose of lactose. We use a combined (13)C/H2 lactose breath test that measures breath (13)CO2 as a measure of lactose digestion in addition to H2 and that has a better sensitivity and specificity than the standard test. The present retrospective study evaluated the results of 1051 (13)C/H2 lactose breath tests to assess the impact on the diagnostic accuracy of measuring breath CH4 in addition to H2 and (13)CO2. Based on the (13)C/H2 breath test, 314 patients were diagnosed with lactase deficiency, 138 with lactose malabsorption or small bowel bacterial overgrowth (SIBO), and 599 with normal lactose digestion. Additional measurement of CH4 further improved the accuracy of the test as 16% subjects with normal lactose digestion and no H2 excretion were found to excrete CH4. These subjects should have been classified as subjects with lactose malabsorption or SIBO. In conclusion, measuring CH4 concentrations has an added value to the (13)C/H2 breath test to identify methanogenic subjects with lactose malabsorption or SIBO. PMID- 26371036 TI - Contribution of Colonic Fermentation and Fecal Water Toxicity to the Pathophysiology of Lactose-Intolerance. AB - Whether or not abdominal symptoms occur in subjects with small intestinal lactose malabsorption might depend on differences in colonic fermentation. To evaluate this hypothesis, we collected fecal samples from subjects with lactose malabsorption with abdominal complaints (LM-IT, n = 11) and without abdominal complaints (LM-T, n = 8) and subjects with normal lactose digestion (NLD, n = 15). Lactose malabsorption was diagnosed using a (13)C-lactose breath test. Colonic fermentation was characterized in fecal samples at baseline and after incubation with lactose for 3 h, 6 h and 24 h through a metabolomics approach using gas chromatography-mass spectrometry (GC-MS). Fecal water cytotoxicity was analyzed using a colorimetric assay. Fecal water cytotoxicity was not different between the three groups (Kruskall-Wallis p = 0.164). Cluster analysis of the metabolite patterns revealed separate clusters for NLD, LM-T and LM-IT samples at baseline and after 24 h incubation with lactose. Levels of 5-methyl-2 furancarboxaldehyde were significantly higher in LM-IT and LM-T compared to NLD whereas those of an unidentified aldehyde were significantly higher in LM-IT compared to LM-T and NLD. Incubation with lactose increased short chain fatty acid (SCFA) concentrations more in LM-IT and LM-T compared to NLD. In conclusion, fermentation patterns were clearly different in NLD, LM-IT and LM-T, but not related to differences in fecal water cytotoxicity. PMID- 26371035 TI - Seronegative Celiac Disease and Immunoglobulin Deficiency: Where to Look in the Submerged Iceberg? AB - In the present narrative review, we analyzed the relationship between seronegative celiac disease (SNCD) and immunoglobulin deficiencies. For this purpose, we conducted a literature search on the main medical databases. SNCD poses a diagnostic dilemma. Villous blunting, intraepithelial lymphocytes (IELs) count and gluten "challenge" are the most reliable markers. Immunohistochemistry/immunofluorescence tissue transglutaminase (tTG)-targeted mucosal immunoglobulin A (IgA) immune complexes in the intestinal mucosa of SNCD patients may be useful. In our experience, tTG-mRNA was similarly increased in seropositive celiac disease (CD) and suspected SNCD, and strongly correlated with the IELs count. This increase is found even in the IELs' range of 15-25/100 enterocytes, suggesting that there may be a "grey zone" of gluten-related disorders. An immune deregulation (severely lacking B-cell differentiation) underlies the association of SNCD with immunoglobulin deficiencies. Therefore, CD may be linked to autoimmune disorders and immune deficits (common variable immunodeficiency (CVID)/IgA selective deficiency). CVID is a heterogeneous group of antibodies dysfunction, whose association with CD is demonstrated only by the response to a gluten-free diet (GFD). We hypothesized a familial inheritance between CD and CVID. Selective IgA deficiency, commonly associated with CD, accounts for IgA-tTG seronegativity. Selective IgM deficiency (sIgMD) is rare (<300 cases) and associated to CD in 5% of cases. We diagnosed SNCD in a patient affected by sIgMD using the tTG-mRNA assay. One-year GFD induced IgM restoration. This evidence, supporting a link between SNCD and immunoglobulin deficiencies, suggests that we should take a closer look at this association. PMID- 26371037 TI - Association of Nut Consumption with Cardiometabolic Risk Factors in the 2008/2009 New Zealand Adult Nutrition Survey. AB - Nut consumption has been associated with improvements in risk factors for chronic disease in populations within North America, Europe and Iran. This relationship has not been investigated in New Zealand (NZ). The associations between nut consumption and cardiometabolic risk factors among New Zealanders were examined. Data from the 24-h diet recalls of 4721 participants from the NZ Adult Nutrition Survey 2008/2009 (2008/2009 NZANS) were used to determine whole and total nut intake. Anthropometric data and blood pressure were collected, as well as blood samples analysed for total cholesterol (total-C) and HDL cholesterol (HDL-C), glycated haemoglobin (HbA1c), C-reactive protein (CRP) and folate. Participants were classified according to their five-year cardiovascular disease (CVD) risk. Both whole and total nut consumers had significantly lower weight, body mass index (BMI), waist circumference and central adiposity than non-nut consumers (all p <= 0.044). Whole blood, serum and red blood cell folate concentrations were significantly higher among whole nut consumers compared to non-whole nut consumers (all p <= 0.014), with only serum folate higher in total nut consumers compared to non-total nut consumers (p = 0.023). There were no significant differences for blood pressure, total-C, HDL-C and HbA1c; however, significant negative associations between total nut consumption and CVD risk category (p < 0.001) and CRP (p = 0.045) were apparent. Nut consumption was associated with more favourable body composition and a number of risk factors, which could collectively reduce chronic disease. PMID- 26371039 TI - Food Habits, Lifestyle Factors and Mortality among Oldest Old Chinese: The Chinese Longitudinal Healthy Longevity Survey (CLHLS). AB - There are few studies reporting the association between lifestyle and mortality among the oldest old in developing countries. We examined the association between food habits, lifestyle factors and all-cause mortality in the oldest old (>=80 years) using data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS). In 1998/99, 8959 participants aged 80 years and older took part in the baseline survey. Follow-up surveys were conducted every two to three years until 2011. Food habits were assessed using an in-person interview. Deaths were ascertained from family members during follow-up. Cox and Laplace regression were used to assess the association between food habits, lifestyle factors and mortality risk. There were 6626 deaths during 31,926 person-years of follow-up. Type of staple food (rice or wheat) was not associated with mortality. Daily fruit and vegetable intake was inversely associated with a higher mortality risk (hazard ratios (HRs): 0.85 (95% CI (confidence interval) 0.77-0.92), and 0.74 (0.66-0.83) for daily intake of fruit and vegetables, respectively). There was a positive association between intake of salt-preserved vegetables and mortality risk (consumers had about 10% increase of HR for mortality). Fruit and vegetable consumption were inversely, while intake of salt-preserved vegetables positively, associated with mortality risk among the oldest old. Undertaking physical activity is beneficial for the prevention of premature death. PMID- 26371038 TI - Involvement of the Niacin Receptor GPR109a in the LocalControl of Glucose Uptake in Small Intestine of Type 2Diabetic Mice. AB - Niacin is a popular nutritional supplement known to reduce the risk of cardiovascular diseases by enhancing high-density lipoprotein levels. Despite such health benefits, niacin impairs fasting blood glucose. In type 2 diabetes (T2DM), an increase in jejunal glucose transport has been well documented; however, this is intriguingly decreased during niacin deficient state. In this regard, the role of the niacin receptor GPR109a in T2DM jejunal glucose transport remains unknown. Therefore, the effects of diabetes and high-glucose conditions on GPR109a expression were studied using jejunal enterocytes of 10-week-old m+/db and db/db mice, as well as Caco-2 cells cultured in 5.6 or 25.2 mM glucose concentrations. Expression of the target genes and proteins were quantified using real-time polymerase chain reaction (RT-PCR) and Western blotting. Glucose uptake in Caco-2 cells and everted mouse jejunum was measured using liquid scintillation counting. 10-week T2DM increased mRNA and protein expression levels of GPR109a in jejunum by 195.0% and 75.9%, respectively, as compared with the respective m+/db control; high-glucose concentrations increased mRNA and protein expression of GPR109a in Caco-2 cells by 130.2% and 69.0%, respectively, which was also confirmed by immunohistochemistry. In conclusion, the enhanced GPR109a expression in jejunal enterocytes of T2DM mice and high-glucose treated Caco-2 cells suggests that GPR109a is involved in elevating intestinal glucose transport observed in diabetes. PMID- 26371040 TI - Menu Planning in Residential Aged Care-The Level of Choice and Quality of Planning of Meals Available to Residents. AB - BACKGROUND: Choice of food is an imperative aspect of quality of life for residents in Residential Aged Care Homes (RACHs), where overall choice and control is diminished upon entering a home to receive care. The purpose of this study was to examine the current strategies of menu planning in a range of RACHs in Australia, and whether this facilitated appropriate levels of choice for residents receiving texture modified and general diets. METHODS: The study comprised a National Menu Survey using a new survey instrument collecting general information about the RACH and foodservice system, menu information and staffing information (n = 247); a national menu analysis (n = 161) and an observational case study of 36 meal environments. RESULTS: Choice was low for the entire sample, but particularly for those receiving pureed texture modified diets. Evidence of menu planning to facilitate the inclusion of choice and alternatives was limited. DISCUSSION: Regulation and monitoring of the Australian Aged Care Accreditation Standards needs to be strengthened to mandate improvement of the choice and variety offered to residents, particularly those on pureed texture modified diets. Further research on how menu choice and a lack of variety in meals affects the quality of life residents is needed in this context, but current evidence suggests the effect would be detrimental and undermine resident autonomy and nutritional status. PMID- 26371042 TI - Aflatoxin B1 Detection Using a Highly-Sensitive Molecularly-Imprinted Electrochemical Sensor Based on an Electropolymerized Metal Organic Framework. AB - A sensitive electrochemical molecularly-imprinted sensor was developed for the detection of aflatoxin B1 (AFB1), by electropolymerization of p-aminothiophenol functionalized gold nanoparticles in the presence of AFB1 as a template molecule. The extraction of the template leads to the formation of cavities that are able to specifically recognize and bind AFB1 through pi-pi interactions between AFB1 molecules and aniline moities. The performance of the developed sensor for the detection of AFB1 was investigated by linear sweep voltammetry using a hexacyanoferrate/hexacyanoferrite solution as a redox probe, the electron transfer rate increasing when the concentration of AFB1 increases, due to a p doping effect. The molecularly-imprinted sensor exhibits a broad linear range, between 3.2 fM and 3.2 uM, and a quantification limit of 3 fM. Compared to the non-imprinted sensor, the imprinting factor was found to be 10. Selectivity studies were also performed towards the binding of other aflatoxins and ochratoxin A, proving good selectivity. PMID- 26371041 TI - Lifestyle Patterns Are Associated with Elevated Blood Pressure among Qatari Women of Reproductive Age: A Cross-Sectional National Study. AB - Women of childbearing age are particularly vulnerable to the adverse effects of elevated blood pressure (BP), with dietary and lifestyle habits being increasingly recognized as important modifiable environmental risk factors for this condition. Using data from the National STEPwise survey conducted in Qatar in year 2012, we aimed to examine lifestyle patterns and their association with elevated BP among Qatari women of childbearing age (18-45 years). Socio demographic, lifestyle, dietary, anthropometric and BP data were used (n = 747). Principal component factor analysis was applied to identify the patterns using the frequency of consumption of 13 foods/food groups, physical activity level, and smoking status. Multivariate logistic regression analyses were used to evaluate the association of the identified lifestyle patterns with elevated BP and to examine the socio-demographic correlates of these patterns. Three lifestyle patterns were identified: a "healthy" pattern characterized by intake of fruits, natural juices, and vegetables; a "fast food & smoking" pattern characterized by fast foods, sweetened beverages, and sweets, in addition to smoking; and a "traditional sedentary" pattern which consisted of refined grains, dairy products, and meat in addition to low physical activity. The fast food & smoking and the traditional & sedentary patterns were associated with an approximately 2-fold increase in the risk of elevated BP in the study population. The findings of this study highlight the synergistic effect that diet, smoking and physical inactivity may have on the risk of elevated BP among Qatari women. PMID- 26371043 TI - Development of a Rapid LC-MS/MS Method for the Determination of Emerging Fusarium mycotoxins Enniatins and Beauvericin in Human Biological Fluids. AB - A novel method for the simultaneous determination of enniatins A, A1, B and B1 and beauvericin, both in human urine and plasma samples, was developed and validated. The method consisted of a simple and easy pretreatment, specific for each matrix, followed by solid phase extraction (SPE) and detection by high performance liquid chromatography-tandem mass spectrometry with an electrospray ion source. The optimized SPE method was performed on graphitized carbon black cartridges after suitable dilution of the extracts, which allowed high mycotoxin absolute recoveries (76%-103%) and the removal of the major interferences from the matrix. The method was extensively evaluated for plasma and urine samples separately, providing satisfactory results in terms of linearity (R2 of 0.991 0.999), process efficiency (>81%), trueness (recoveries between 85% and 120%), intra-day precision (relative standard deviation, RSD < 18%), inter-day precision (RSD < 21%) and method quantification limits (ranging between 20 ng.L(-1) and 40 ng.L(-1) in plasma and between 5 ng.L(-1) and 20 ng.L(-1) in urine). Finally, the highly sensitive validated method was applied to some urine and plasma samples from different donors. PMID- 26371044 TI - MicroRNA Polymorphisms in Cancer: A Literature Analysis. AB - Single nucleotide polymorphisms (SNPs) located in microRNA (miRNA) genes (miR SNPs) have attracted increasing attention in recent years due to their involvement in the development of various types of cancer. Therefore, a systematic review on this topic was needed. From 55 scientific publications we collected 20 SNPs, which are located within 18 miRNA encoding genes and have been associated with 16 types of cancer. Among 20 miRNA gene polymorphisms 13 are located within the premature miRNA region, five within mature, and two within mature seed miRNA region. We graphically visualized a network of miRNA-cancer associations which revealed miRNA genes and cancer types with the highest number of connections. Our study showed that, despite a large number of variations currently known to be located within miRNA genes in humans, most of them have not yet been tested for association with cancer. MicroRNA SNPs collected in this study represent only 0.43% of known miRNA gene variations (20/4687). Results of the present study will be useful to researchers investigating the clinical use of miRNAs, such as the roles of miRNAs as diagnostic markers and therapeutic targets. PMID- 26371045 TI - The Evolution of Therapies in Non-Small Cell Lung Cancer. AB - The landscape of advanced non-small lung cancer (NSCLC) therapies has rapidly been evolving beyond chemotherapy over the last few years. The discovery of oncogenic driver mutations has led to new ways in classifying NSCLC as well as offered novel therapeutic targets for anticancer therapy. Targets such as epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) gene rearrangements have successfully been targeted with appropriate tyrosine kinase inhibitors (TKIs). Other driver mutations such as ROS, MET, RET, BRAF have also been investigated with targeted agents with some success in the early phase clinical setting. Novel strategies in the field of immune-oncology have also led to the development of inhibitors of cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed death-1 receptor (PD-1), which are important pathways in allowing cancer cells to escape detection by the immune system. These inhibitors have been successfully tried in NSCLC and also now bring the exciting possibility of long term responses in advanced NSCLC. In this review recent data on novel targets and therapeutic strategies and their future prospects are discussed. PMID- 26371046 TI - Epigenetic Heterogeneity of B-Cell Lymphoma: DNA Methylation, Gene Expression and Chromatin States. AB - Mature B-cell lymphoma is a clinically and biologically highly diverse disease. Its diagnosis and prognosis is a challenge due to its molecular heterogeneity and diverse regimes of biological dysfunctions, which are partly driven by epigenetic mechanisms. We here present an integrative analysis of DNA methylation and gene expression data of several lymphoma subtypes. Our study confirms previous results about the role of stemness genes during development and maturation of B-cells and their dysfunction in lymphoma locking in more proliferative or immune-reactive states referring to B-cell functionalities in the dark and light zone of the germinal center and also in plasma cells. These dysfunctions are governed by widespread epigenetic effects altering the promoter methylation of the involved genes, their activity status as moderated by histone modifications and also by chromatin remodeling. We identified four groups of genes showing characteristic expression and methylation signatures among Burkitt's lymphoma, diffuse large B cell lymphoma, follicular lymphoma and multiple myeloma. These signatures are associated with epigenetic effects such as remodeling from transcriptionally inactive into active chromatin states, differential promoter methylation and the enrichment of targets of transcription factors such as EZH2 and SUZ12. PMID- 26371047 TI - Ecology and Evolution of the Human Microbiota: Fire, Farming and Antibiotics. AB - Human activities significantly affect all ecosystems on the planet, including the assemblages that comprise our own microbiota. Over the last five million years, various evolutionary and ecological drivers have altered the composition of the human microbiota, including the use of fire, the invention of agriculture, and the increasing availability of processed foods after the Industrial Revolution. However, no factor has had a faster or more direct effect than antimicrobial agents. Biocides, disinfectants and antibiotics select for individual cells that carry resistance genes, immediately reducing both overall microbial diversity and within-species genetic diversity. Treated individuals may never recover their original diversity, and repeated treatments lead to a series of genetic bottlenecks. The sequential introduction of diverse antimicrobial agents has selected for increasingly complex DNA elements that carry multiple resistance genes, and has fostered their spread through the human microbiota. Practices that interfere with microbial colonization, such as sanitation, Caesarian births and bottle-feeding, exacerbate the effects of antimicrobials, generating species-poor and less resilient microbial assemblages in the developed world. More and more evidence is accumulating that these perturbations to our internal ecosystems lie at the heart of many diseases whose frequency has shown a dramatic increase over the last half century. PMID- 26371048 TI - Emotion Regulation in Adolescent Males with Attention-Deficit Hyperactivity Disorder: Testing the Effects of Comorbid Conduct Disorder. AB - Although attention-deficit hyperactivity disorder (ADHD) has been linked to emotion dysregulation, few studies have experimentally investigated this whilst controlling for the effects of comorbid conduct disorder (CD). Economic decision making games that assess how individuals respond to offers varying in fairness have been used to study emotion regulation. The present study compared adolescent boys with ADHD (n = 90), ADHD + CD (n = 94) and typical controls (n = 47) on the Ultimatum Game and examined the contribution of ADHD and CD symptom scores and callous and unemotional traits to acceptance levels of unfair offers. There were no significant differences in acceptance rates of fair and highly unfair offers between groups, and only boys with ADHD did not significantly differ from the controls. However, the subgroup of boys with ADHD and additional high levels of aggressive CD symptoms rejected significantly more ambiguous (i.e., moderately unfair) offers than any other subgroup, suggesting impaired emotion regulation in those with ADHD and aggressive CD. Correlations within the CD group showed that the rejection rate to moderately unfair offers was predicted by aggressive CD symptom severity, but not callous and unemotional traits. These findings highlight the fact that ADHD is a heterogeneous condition from an emotion regulation point of view. PMID- 26371049 TI - Lipidomics to Assess Omega 3 Bioactivity. AB - How can we resolve the conflict between the strong epidemiological evidence pointing to the usefulness of fish-and, thus, omega 3-consumption with the debacle of supplementation trials? One potential explanation is that the null results obtained thus far are the consequences of ill-contrived investigations that do not allow us to conclude on the effects (or lack thereof) of omega 3 fatty acid supplementation. One potential solution is through the use of lipidomics, which should prove very useful to screen suitable patients and to correlate plasma (or red blood cells, or whole blood, or phospholipid) fatty acid profile with outcomes. This has never been done in omega 3 trials. The wise use of lipidomics should be essential part of future omega 3 trials and would help in untangling this current riddle. PMID- 26371050 TI - Non-Proteinuric Diabetic Nephropathy. AB - Diabetic nephropathy patients traditionally show significant macroalbuminuria prior to the development of renal impairment. However, this clinical paradigm has recently been questioned. Epidemiological surveys confirm that chronic kidney disease (CKD) diagnosed by a low glomerular filtration rate (GFR) is more common in diabetic patients than in the non-diabetic population but a low number of patients had levels of proteinuria above that which traditionally defines overt diabetic nephropathy (>500 mg/g). The large number of patients with low levels of proteinuria suggests that the traditional clinical paradigm of overt diabetic nephropathy is changing since it does not seem to be the underlying renal lesion in most of diabetic subjects with CKD. PMID- 26371051 TI - Hypothalamic Obesity in Craniopharyngioma Patients: Disturbed Energy Homeostasis Related to Extent of Hypothalamic Damage and Its Implication for Obesity Intervention. AB - Hypothalamic obesity (HO) occurs in patients with tumors and lesions in the medial hypothalamic region. Hypothalamic dysfunction can lead to hyperinsulinemia and leptin resistance. This review is focused on HO caused by craniopharyngiomas (CP), which are the most common childhood brain tumors of nonglial origin. Despite excellent overall survival rates, CP patients have substantially reduced quality of life because of significant long-term sequelae, notably severe obesity in about 50% of patients, leading to a high rate of cardiovascular mortality. Recent studies reported that both hyperphagia and decreased energy expenditure can contribute to severe obesity in HO patients. Recognized risk factors for severe obesity include large hypothalamic tumors or lesions affecting several medial and posterior hypothalamic nuclei that impact satiety signaling pathways. Structural damage in these nuclei often lead to hyperphagia, rapid weight gain, central insulin and leptin resistance, decreased sympathetic activity, low energy expenditure, and increased energy storage in adipose tissue. To date, most efforts to treat HO have shown disappointing long-term success rates. However, treatments based on the distinct pathophysiology of disturbed energy homeostasis related to CP may offer options for successful interventions in the future. PMID- 26371052 TI - Effectiveness of Vitamin-E-Doped Polyethylene in Joint Replacement: A Literature Review. AB - Since polyethylene is one of the most frequently used biomaterials, such as in bearing components in joint arthroplasty, strong efforts have been made to improve the design and material properties over the last decades. Antioxidants, such as vitamin-E, seem to be a promising alternative to further increase durability and reduce polyethylene wear and degradation in the long-term. Nevertheless, even if several promising in vitro results are available, there is yet no clinical evidence that vitamin-E polyethylenes show these advantages in vivo. The aim of this paper was to provide a comprehensive overview on the current knowledge regarding the biological and mechanical proprieties of this biomaterial, underlying the in vitro and in vivo evidence for effectiveness of vitamin-E-doped polyethylene in joint arthroplasty. PMID- 26371054 TI - Self-Preservation in Both Sides: Pathology of Spiritual Care in Iran. AB - The aim of this study was to create a deeper understanding of the variables that may restrain or progress spiritual care in Iran. This manuscript provides an in depth description of barriers to delivering spiritual care by nurses as well as patients' compensatory mechanisms against deprivation from spiritual care termed "self-preservation in both sides" emerged from an empirical study. It brings issues such as structural, hierarchical, social and personal concerns, which may prevent advancing spirituality within health care, to light. Thirty-five participants, nurses (n = 10), patients (n = 22) and their relatives (n = 3), took part in this study, and data were analyzed using qualitative content analysis method. Being aware of these results may help nurses and healthcare professionals to engage with and overcome some of the structural, hierarchical and social variables affecting spiritual care. PMID- 26371055 TI - Activation of 5-HT2A/C receptor reduces glycine receptor-mediated currents in cultured auditory cortical neurons. AB - Glycine receptors (GlyRs) permeable to chloride only mediate tonic inhibition in the cerebral cortex where glycinergic projection is completely absent. The functional modulation of GlyRs was largely studied in subcortical brain regions with glycinergic transmissions, but the function of cortical GlyRs was rarely addressed. Serotonin could broadly modulate many ion channels through activating 5-HT2 receptor, but whether cortical GlyRs are subjected to serotonergic modulation remains unexplored. The present study adopted patch clamp recordings to examine functional regulation of strychnine-sensitive GlyRs currents in cultured cortical neurons by DOI (2,5-Dimethoxy-4-iodoamphetamine), a 5-HT2A/C receptor agonist. DOI caused a concentration-dependent reduction of GlyR currents with unchanged reversal potential. This reduction was blocked by the selective receptor antagonists (ritanserin and risperidone) and G protein inhibitor (GDP beta-s) demonstrated that the reducing effect of DOI on GlyR current required the activation of 5-HT2A/C receptors. Strychnine-sensitive tonic currents revealed the inhibitory tone mediated by nonsynaptic GlyRs, and DOI similarly reduced the tonic inhibition. The impaired microtube-dependent trafficking or clustering of GlyRs was thought to be involved in that nocodazole as a microtube depolymerizing drug largely blocked the inhibition mediated by 5-HT2A/C receptors. Our results suggested that activation of 5-HT2A/C receptors might suppress cortical tonic inhibition mediated by GlyRs, and the findings would provide important insight into serotonergic modulation of tonic inhibition mediated by GlyRs, and possibly facilitate to develop the therapeutic treatment of neurological diseases such as tinnitus through regulating cortical GlyRs. PMID- 26371057 TI - Self-assembly of ultrathin Cu2MoS4 nanobelts for highly efficient visible light driven degradation of methyl orange. AB - We demonstrate ultrathin self-assembled Cu2MoS4 nanobelts synthesized by using Cu2O as the starting sacrificial template via a hydrothermal method. The nanobelts exhibit strong light absorption over a broad wavelength spectrum, suggesting their potential application as photocatalysts. The photocatalytic activity of nanobelts is evaluated by the degradation of Methyl Orange (MO) dye under visible light irradiation. Notably, the nanobelts can completely degrade 100 mL of 15 mg mL(-1) MO in 20 minutes with excellent recycling and structural stability, suggesting their excellent photocatalytic performance. In comparison with a sheet-like sample, the high efficiency of the self-assembled Cu2MoS4 nanobelts is attributed to a high surface area and a unique band gap, agreeing with the nitrogen adsorption analysis and photoluminescence spectra. This study offers a self-assembled synthetic route to create new multifunctional nanoarchitectures composed of atomic layers, and thus may open a window for greatly extending potential applications in water pollution treatment, photocatalytic water-splitting, solar cells and other related fields. PMID- 26371056 TI - In vitro fertilization in women under 35: counseling should differ by age. AB - PURPOSE: The aim of this study is to evaluate the outcomes of in vitro fertilization (IVF), including cumulative live birth rate, among women <25 years, 25 to <30 years, and 30 to <35 years. METHODS: A retrospective cohort study of all women 18 to <35 years of age at their first fresh-embryo, non-donor IVF cycle from January 1995 through December 2012 at a single center was conducted. A competing-risk regression model was used to estimate the cumulative probability and 95 % confidence interval (CI) of the first live birth in up to 6 cycles during the study period with IVF cycle number as the time metric. RESULTS: Among 7243 women who underwent 16,792 cycles, there were 163 (2.3 %) women <25 years, 1691 (23.3 %) women 25 to <30 years, and 5389 (74.4 %) women 30 to <35 years. Women <25 years had the lowest cumulative live birth rate after each cycle, followed by women 30 to <35 years. In both groups, the cumulative live birth rate after 6 cycles was significantly lower than that of women 25 to <30 years; these rates were 58 % (95 % CI 0.51-0.66) among women <25 years, 69 % (95 % CI 0.67 0.71) among women 25 to <30 years, and 64 % (95 % CI 0.63-0.65) among women 30 to <35 years. CONCLUSIONS: Our findings are consistent with other reports of less favorable IVF treatment outcomes in women <25 years of age following their first IVF cycle. This indicates that there are underlying factors in couples with a female <25 years of age that should lead to different treatment counseling when they attempt IVF. PMID- 26371053 TI - Splicing Regulation of Pro-Inflammatory Cytokines and Chemokines: At the Interface of the Neuroendocrine and Immune Systems. AB - Alternative splicing plays a key role in posttranscriptional regulation of gene expression, allowing a single gene to encode multiple protein isoforms. As such, alternative splicing amplifies the coding capacity of the genome enormously, generates protein diversity, and alters protein function. More than 90% of human genes undergo alternative splicing, and alternative splicing is especially prevalent in the nervous and immune systems, tissues where cells need to react swiftly and adapt to changes in the environment through carefully regulated mechanisms of cell differentiation, migration, targeting, and activation. Given its prevalence and complexity, this highly regulated mode of gene expression is prone to be affected by disease. In the following review, we look at how alternative splicing of signaling molecules-cytokines and their receptors-changes in different pathological conditions, from chronic inflammation to neurologic disorders, providing means of functional interaction between the immune and neuroendocrine systems. Switches in alternative splicing patterns can be very dynamic and can produce signaling molecules with distinct or antagonistic functions and localization to different subcellular compartments. This newly discovered link expands our understanding of the biology of immune and neuroendocrine cells, and has the potential to open new windows of opportunity for treatment of neurodegenerative disorders. PMID- 26371058 TI - Dysregulated expression of miR-101b and miR-26b lead to age-associated increase in LPS-induced COX-2 expression in murine macrophage. AB - Aging is the natural process of decline in physiological structure and function of various molecules, cells, tissues, and organs. Growing evidence indicates that increased immune genetic diversity and dysfunction of immune system cause aging related pathophysiological process with the growth of age. In the present study, we observed that LPS-induced higher activation of cyclooxygenase (COX)-2 promoter is associated with the upregulated binding activity of nuclear factor kappa B (NF kappaB) in peritoneal macrophages of aged mice than young ones. Additionally, COX 2 is a direct target of miR-101b and miR-26b in the macrophages. Significant upregulation of miR-101b and miR-26b effectively prevented LPS-induced excessive expression of COX-2 in the young mice. Because these negative regulatory factors were unresponsive to LPS stimulation, the levels of COX-2 were markedly higher in the macrophages of aged mice. Further study showed that NF-kappaB activation contributed to the increase in the expression of miR-101b and miR-26b in the LPS stimulated macrophages of young mice, but not aged ones. Moreover, histone deacetylase (HDAC) inhibitor trichostatin A (TSA) upregulated expression of miR 101b and miR-26b in the aged mouse macrophages only, but not the young cells. This demonstrated that HDAC suppressed the expression of miR-101b and miR-26b in the LPS-treated macrophages of aged mice and contributed to the aging process. TSA-induced increased expression of miR-101b and miR-26b could further suppress COX-2 expression. These findings provide novel evidence on the regulation of immune senescence and miR-101b and miR-26b, which might be promising targets in treating aged-related inflammatory diseases. Epigenetic regulation of the microRNAs (miRNAs) provides an important evidence for the treatment of innate inflammatory disease with HDAC inhibitors in elderly. PMID- 26371060 TI - Development of a microfluidic platform with integrated power splitting waveguides for optogenetic neural cell stimulation. AB - We present a microfluidic platform with integrated power splitting waveguides for optogenetic neural cell stimulation. A liquid-core/PDMS-cladding waveguide with a power splitter design was integrated with a neural cell culture chamber to provide a simple way of precise localized optical stimulation. The parallel on chip excitation of individual neural cells using a single optical fiber input is demonstrated for optogenetic neural cell studies, and the excitation of each individual waveguide can be independently controlled by pneumatic valves. Light delivery and loss mechanisms through the waveguides were studied and characterized. The waveguide power splitter platform is capable of providing sufficient irradiance to evoke spikes in ChR2-expressing neural cells. The system enables high-resolution stimulation of neural cells in a controllable manner. The microfluidic platform described here represents a novel methodology for studying optogenetics in a compact integrated system with high spatial resolutions. PMID- 26371059 TI - Improving healthspan via changes in gut microbiota and fermentation. AB - Dietary resistant starch impact on intestinal microbiome and improving healthspan is the topic of this review. In the elderly population, dietary fiber intake is lower than recommended. Dietary resistant starch as a source of fiber produces a profound change in gut microbiota and fermentation in animal models of aging. Dietary resistant starch has the potential for improving healthspan in the elderly through multiple mechanisms as follows: (1) enhancing gut microbiota profile and production of short-chain fatty acids, (2) improving gut barrier function, (3) increasing gut peptides that are important in glucose homeostasis and lipid metabolism, and (4) mimicking many of the effects of caloric restriction including upregulation of genes involved in xenobiotic metabolism. PMID- 26371061 TI - Effect of magnesium ion on crt gene expression in improving carotenoid yield of Rhodobacter sphaeroides. AB - This study aimed at increasing carotenoid yield of Rhodobacter sphaeroides in wastewater treatment by adding magnesium ion (Mg(2+)). Results showed that Mg(2+) could improve R. sphaeroides biomass and carotenoid yield effectively. The highest carotenoid yield of 4.83 +/- 0.14 mg/g biomass and biomass production of 3900 +/- 180 mg/L were achieved at optimal Mg(2+) concentration of 15 mmol/L. Mechanism analysis revealed that Mg(2+) could promote carotenoid production by regulating the expressions of crt genes. Up-regulation of crtBDA genes improved carotenoid biosynthesis of R. sphaeroides. PMID- 26371063 TI - Clinical Significance of Endothelial Dysfunction in Essential Hypertension. AB - The endothelium is recognized as a major determinant of vascular physiology and pathophysiology. Over the last few decades, a plethora of studies have implicated endothelial dysfunction in the progression of atherosclerosis and the subclinical target organ damage observed in essential hypertension. However, the clinical significance of diagnosing endothelial dysfunction in patients with essential hypertension remains under investigation. Although a number of vascular and non vascular markers of endothelial dysfunction have been proposed, there is an ongoing quest for a marker in the clinical setting that is optimal, inexpensive, and reproducible. In addition, endothelial dysfunction emerges as a promising therapeutic target of agents that are readily available in clinical practice. In this context, a better understanding of its role in essential hypertension becomes of great importance. Here, we aim to investigate the clinical significance of endothelial dysfunction in essential hypertension by accumulating novel data on (a) early diagnosis using robust markers with prognostic value in cardiovascular risk prediction, (b) the association of endothelial dysfunction with subclinical vascular organ damage, and (c) potential therapeutic targets. PMID- 26371064 TI - HIV-1 group O infection in Cameroon from 2006 to 2013: Prevalence, genetic diversity, evolution and public health challenges. AB - The human immunodeficiency virus, HIV, is characterized by a tremendously high genetic diversity, leading to the currently known circulating HIV types, groups, subtypes, and recombinant forms. HIV-1 group O is one of the most diverse forms of HIV-1 and has been so far related to Cameroon or individuals originating from Cameroon. In this study, we investigated in Cameroon, the evolution of this viral group from 2006 to 2013, in terms of prevalence, genetic diversity and public health implications. Our results confirmed the predominance of HIV-1 group M (98.5%), a very low prevalence (<0.02%) for HIV-1 group N and P, and HIV-2 in this country. HIV-1 group O was found at around 0.6% (95% confidence interval: 0.4-0.8%), indicating that the frequency of this virus in Cameroon has remained stable over the last decades. However, we found an extensive high genetic diversity within this HIV-1 group, that resulted from previous steady increase on the effective number of HIV-1 group O infections through time, and the current distribution of the circulating viral strains still does not allow classification as subtypes. The frequency of dual infections with HIV-1 group M and group O was 0.8% (95% confidence interval: 0.6-1.0%), but we found no recombinant forms in co infected patients. Natural resistance to integrase inhibitors was not identified, although we found several mutations considered as natural polymorphisms. Our study shows that infections with HIV-1 group O can be adequately managed in countries where the virus circulates, but this complex virus still represents a challenge for diagnostics and monitoring strategies. PMID- 26371065 TI - Phylogenetic analyses of influenza A (H1N1)pdm09 hemagglutinin gene during and after the pandemic event in Brazil. AB - Pandemic influenza A H1N1 [A(H1N1)pdm09] was first detected in Brazil in May 2009, and spread extensively throughout the country causing a peak of infection during June to August 2009. Since then, it has continued to circulate with a seasonal pattern, causing high rates of morbidity and mortality. Over this period, the virus has continually evolved with the accumulation of new mutations. In this study we analyze the phylogenetic relationship in a collection of 220 A(H1N1)pdm09 hemagglutinin (HA) gene sequences collected during and after the pandemic period (2009 to 2014) in Brazil. In addition, we have looked for evidence of viral polymorphisms associated with severe disease and compared the range of viral variants with the vaccine strain (A/California/7/2009) used throughout this period. The phylogenetic analyses in this study revealed the circulation of at least eight genetic groups in Brazil. Two (G6-pdm and G7-pdm) co-circulated during the pandemic period, showing an early pattern of viral diversification with a low genetic distance from vaccine strain. Other phylogenetic groups, G5, G6 (including 6B, 6C and 6D subgroups), and G7 were found in the subsequent epidemic seasons from 2011 to 2014. These viruses exhibited more amino acid differences from the vaccine strain with several substitutions at the antigenic sites. This is associated with a theoretical decrease in the vaccine efficacy. Furthermore, we observed that the presence of any polymorphism at residue 222 of the HA gene was significantly associated with severe/fatal cases, reinforcing previous reports that described this residue as a potential virulence marker. This study provides new information about the circulation of some viral variants in Brazil, follows up potential genetic markers associated with virulence and allows infer if the efficacy of the current vaccine against more recent A(H1N1)pdm09 strains may be reduced. PMID- 26371066 TI - Lethal disease in infant and juvenile Syrian hamsters experimentally infected with Imjin virus, a newfound crocidurine shrew-borne hantavirus. AB - To gain insights into the pathogenicity of Imjin virus (MJNV), a newfound hantavirus isolated from the Ussuri white-toothed shrew (Crocidura lasiura), groups of Syrian hamsters (Mesocricetus auratus) of varying ages (<1, 5, 10, 14, 21, 35 and 56 days) were inoculated by the intraperitoneal route with 1000 pfu of MJNV strains 04-55 and 05-11. MJNV-infected Syrian hamsters, aged 21 days or less, exhibited reduced activity, weight loss, respiratory distress, hind-limb paralysis and seizures. Death ensued 1 to 6 days after onset of clinical disease. MJNV RNA was detected in brain and other major organs by RT-PCR and real time PCR. Histopathological examination showed alveolar hemorrhage, interstitial pneumonia and severe pulmonary congestion; focal hepatic necrosis and portal inflammation; and acute meningoencephalitis. By immunohistochemistry, MJNV antigen was detected in pulmonary microvascular endothelial cells and glial cells. Older hamsters (35 and 56 days of age) developed subclinical infection without histopathological changes. Future studies are warranted to determine the pathophysiologic bases for the differential age susceptibility of Syrian hamsters to lethal MJNV disease. PMID- 26371068 TI - Pattern Formation in the Bromate-Sulfite-Ferrocyanide Reaction. AB - Mixed Landolt-type pH oscillators are versatile systems that allow the experimental study of a wide range of nonlinear phenomena including multistability, oscillations, and spatiotemporal patterns. We report on the dynamics of the bromate-sulfite-ferrocyanide reaction operated in a open one-side fed reactor, where spatial bistability, spatiotemporal oscillations, front and Turing-type patterns have been observed. The role of different experimental parameters, like the input flow concentrations of the hydrogen and the ferrocyanide ions, the temperature and the thickness of the gel medium (which affects the rate of the diffusive feed) have been investigated. We point out that all these parameters can be efficiently used to control the spatiotemporal dynamics. We show that the increase of ionic strength stabilizes the uniform states at the expense of the patterned one. Some general aspects of the spatiotemporal dynamics of mixed Landolt type systems, which are based on the oxidation of sulfite ions by strong oxidants, are emphasized. PMID- 26371067 TI - Genotype diversity and distribution of Orientia tsutsugamushi in scrub typhus patients and rodents in Shandong, northern China. AB - Orientia tsutsugamushi, the etiologic agent of scrub typhus, is transmitted to humans through the bites of infected chiggers. To identify the genotypes of O.tsutsugamushi and their geographical distribution in Shandong, 236 patient's samples and 1606 captured rodents were collected in major-endemic regions of Shandong Province from June 2013 to December 2014. Sequences were determined for the 56-kDa TSA gene, and the relationship between these sequences and those previously determined was assessed. Two genotypes out of 5 previously reported in Shandong were identified, i.e. Kawasaki-related and STA-07. The Kawasaki-related genotype was predominant (82.1% (23/28) in human and 50% (5/10) in rodents), with wide distribution through the endemic areas of Shandong Province. The STA-07 was confined to Tai'an, Linyi and Qingdao districts. The Fuji-related, Shimikoshi related and Karp-related genotypes were not found, while identified in previous studies. For prevention and control of scrub typhus in Shandong, more attention should be paid to surveillance of Kawasaki-related and STA-07 genotypes. PMID- 26371071 TI - An observational study of shift length, crew familiarity, and occupational injury and illness in emergency medical services workers. AB - OBJECTIVES: Emergency medical services (EMS) clinicians are shift workers deployed in two-person teams. Extended shift duration, workplace fatigue, poor sleep and lack of familiarity with teammates are common in the EMS workforce and may contribute to workplace injury. We sought to examine the relationship between shift length and occupational injury while controlling for relevant shift work and teamwork factors. METHODS: We obtained 3 years of shift schedules and occupational injury and illness reports were from 14 large EMS agencies. We abstracted shift length and additional scheduling and team characteristics from shift schedules. We matched occupational injury and illness reports to shift records and used hierarchical logistic regression models to test the relationship between shift length and occupational injury and illness while controlling for teammate familiarity. RESULTS: The cohort contained 966,082 shifts, 4382 employees and 950 outcome reports. Risk of occupational injury and illness was lower for shifts <=8 h in duration (RR 0.70; 95% CI 0.51 to 0.96) compared with shifts >8 and <=12 h. Relative to shifts >8 and <=12 h, risk of injury was 60% greater (RR 1.60; 95% CI 1.22 to 2.10) for employees that worked shifts >16 and <=24 h. CONCLUSIONS: Shift length is associated with increased risk of occupational injury and illness in this sample of EMS shift workers. PMID- 26371072 TI - Stem length in revision total knee arthroplasty. AB - Stems are intramedullary extensions of either the femoral or tibial component of a total knee arthroplasty (TKA) designed to increase the mechanical stability to decrease the risk of aseptic loosening. Biomechanical studies have shown that TKA stems increase the mechanical stability by transferring load over a larger area and thereby reduce strain at the bone-component interface [1-4]. The length of a revision TKA stem is determined by the patient's anatomy and the intended fixation, namely fully cemented or press-fit cortical contact. The advantages and disadvantages of various stem lengths must be weighed against the needs of the patient to achieve an optimal outcome. PMID- 26371073 TI - Particulated articular cartilage for symptomatic chondral defects of the knee. AB - The treatment of focal cartilage defects in the knee remains a challenging clinical problem. One relatively new unique treatment option is particulated articular cartilage, which includes autograft and off-the-shelf allogeneic juvenile grafts. The use of particulated cartilage has the advantage of being a single-stage procedure. In the case of autograft, it is cost efficient, while in the juvenile allograft form, it may have increased proliferative and restorative potentials. Laboratory and clinical data are limited for particulated cartilage grafts; however, there are promising histologic and clinical outcomes. This review provides a summary of the indications, surgical technique, and most up-to date research on particulated cartilage for the repair of symptomatic chondral defects in the knee. PMID- 26371074 TI - Linking microbial community structure and microbial processes: an empirical and conceptual overview. AB - A major goal of microbial ecology is to identify links between microbial community structure and microbial processes. Although this objective seems straightforward, there are conceptual and methodological challenges to designing studies that explicitly evaluate this link. Here, we analyzed literature documenting structure and process responses to manipulations to determine the frequency of structure-process links and whether experimental approaches and techniques influence link detection. We examined nine journals (published 2009 13) and retained 148 experimental studies measuring microbial community structure and processes. Many qualifying papers (112 of 148) documented structure and process responses, but few (38 of 112 papers) reported statistically testing for a link. Of these tested links, 75% were significant and typically used Spearman or Pearson's correlation analysis (68%). No particular approach for characterizing structure or processes was more likely to produce significant links. Process responses were detected earlier on average than responses in structure or both structure and process. Together, our findings suggest that few publications report statistically testing structure-process links. However, when links are tested for they often occur but share few commonalities in the processes or structures that were linked and the techniques used for measuring them. PMID- 26371075 TI - Optimized 14 + 1 receive coil array and position system for 3D high-resolution MRI of dental and maxillomandibular structures. AB - OBJECTIVES: The purpose of this study was to design, build and test a multielement receive coil array and position system, which is optimized for three dimensional (3D) high-resolution dental and maxillomandibular MRI with high patient comfort. METHODS: A 14 + 1 coil array and positioning system, allowing easy handling by the technologists, reproducible positioning of the patients and high patient comfort, was tested with three healthy volunteers using a 3.0-T MRI machine (Siemens Skyra; Siemens Medical Solutions, Erlangen, Germany). High resolution 3D T1 weighted, water excitation T1 weighted and fat-saturated T2 weighted imaging sequences were scanned, and 3D image data were reformatted in different orientations and curvatures to aid diagnosis. RESULTS: The high number of receiving coils and the comfortable positioning of the coil array close to the patient's face provided a high signal-to-noise ratio and allowed high quality, high resolution, 3D image data to be acquired within reasonable scan times owing to the possibility of parallel image acquisition acceleration. Reformatting the isotropic 3D image data in different views is helpful for diagnosis, e.g. panoramic reconstruction. The visibility of soft tissues such as the mandibular canal, nutritive canals and periodontal ligaments was exquisite. CONCLUSIONS: The optimized MRI receive coil array and positioning system for dental and oral maxillofacial imaging provides a valuable tool for detecting and diagnosing pathologies in dental and oral-maxillofacial structures while avoiding radiation dose. The high patient comfort, as achieved by our design, is very crucial, since image artefacts due to movement or failing to complete the examination jeopardize the diagnostic value of MRI examinations. PMID- 26371076 TI - Determination of the mental foramen position in dental radiographs in 18-30 year olds. AB - OBJECTIVES: To determine the radiographic position and reliability of assessing mental foramen (MF) position in relation to premolar crowns in an 18- to 30-year old UK-based population. METHODS: Following ethical approval and a power calculation, the position of the MF was recorded in relation to premolar crowns and apices in 100 dental panoramic tomographs. Positions were assessed by three senior clinicians independently, then by consensus. Data were analysed using descriptive statistics, chi(2) and Fleiss' and Cohen's kappa. RESULTS: Reliability data showed only fair to moderate agreement on independent scoring. Substantial to almost perfect agreement was achieved by consensus, demonstrating the most common position for the MF to be between the first and second premolar teeth when using both premolar crowns (51%) and apices (76%) as reference points. There was a significant difference in the position of the foramen between the left and right sides (p < 0.05), with only 62% of cases showing symmetry. CONCLUSIONS: The most common position for the MF is between the first and second premolar teeth; however, anatomical variation is seen. Use of pre-operative radiographs to relate the position of the MF to premolar crowns may not be reliable. PMID- 26371077 TI - Quantitative and qualitative comparison of MR imaging of the temporomandibular joint at 1.5 and 3.0 T using an optimized high-resolution protocol. AB - OBJECTIVES: To quantitatively and qualitatively compare MRI of the temporomandibular joint (TMJ) using an optimized high-resolution protocol at 3.0 T and a clinical standard protocol at 1.5 T. METHODS: A phantom and 12 asymptomatic volunteers were MR imaged using a 2-channel surface coil (standard TMJ coil) at 1.5 and 3.0 T (Philips Achieva and Philips Ingenia, respectively; Philips Healthcare, Best, Netherlands). Imaging protocol consisted of coronal and oblique sagittal proton density-weighted turbo spin echo sequences. For quantitative evaluation, a spherical phantom was imaged. Signal-to-noise ratio (SNR) maps were calculated on a voxelwise basis. For qualitative evaluation, all volunteers underwent MRI of the TMJ with the jaw in closed position. Two readers independently assessed visibility and delineation of anatomical structures of the TMJ and overall image quality on a 5-point Likert scale. Quantitative and qualitative measurements were compared between field strengths. RESULTS: The quantitative analysis showed similar SNR for the high-resolution protocol at 3.0 T compared with the clinical protocol at 1.5 T. The qualitative analysis showed significantly better visibility and delineation of clinically relevant anatomical structures of the TMJ, including the TMJ disc and pterygoid muscle as well as better overall image quality at 3.0 T than at 1.5 T. CONCLUSIONS: The presented results indicate that expected gains in SNR at 3.0 T can be used to increase the spatial resolution when imaging the TMJ, which translates into increased visibility and delineation of anatomical structures of the TMJ. Therefore, imaging at 3.0 T should be preferred over 1.5 T for imaging the TMJ. PMID- 26371078 TI - The link between radiofrequencies emitted from wireless technologies and oxidative stress. AB - Wireless communication such as cellular telephones and other types of handheld phones working with frequencies of 900MHz, 1800MHz, 2100MHz, 2450MHz have been increasing rapidly. Therefore, public opinion concern about the potential human health hazards of short and long-term effect of exposure to radiofrequency (RF) radiation. Oxidative stress is a biochemical condition, which is defined by the imbalance between reactive oxygen species (ROS) and the anti-oxidative defense. In this review, we evaluated available in vitro and in vivo studies carried out on the relation between RF emitted from mobile phones and oxidative stress. The results of the studies we reviewed here indicated that mobile phones and similar equipment or radars can be thought as a factor, which cause oxidative stress. Even some of them claimed that oxidative stress originated from radiofrequencies can be resulted with DNA damage. For this reason one of the points to think on is relation between mobile phones and oxidative stress. However, more performance is necessary especially on human exposure studies. PMID- 26371079 TI - Margaret McCartney: For better primary care, pay GPs for service. PMID- 26371081 TI - Studying early stages of fibronectin fibrillogenesis in living cells by atomic force microscopy. AB - Fibronectin (FN) is an extracellular matrix protein that can be assembled by cells into large fibrillar networks, but the dynamics of FN remodeling and the transition through intermediate fibrillar stages are incompletely understood. Here we used a combination of fluorescence microscopy and time-lapse atomic force microscopy (AFM) to visualize initial stages of FN fibrillogenesis in living fibroblasts at high resolution. Initial FN nanofibrils form within <5 min of cell matrix contact and subsequently extend at a rate of 0.25 MUm/min at sites of cell membrane retraction. FN nanofibrils display a complex linear array of globular features spaced at varying distances, indicating the coexistence of different conformational states within the fibril. In some cases, initial fibrils extended in discrete increments of ~ 800 nm during a series of cyclical membrane retractions, indicating a stepwise fibrillar extension mechanism. In presence of Mn(2+), a known activator of integrin adhesion to FN, fibrillogenesis was accelerated almost threefold to 0.68 MUm/min and fibrillar dimensions were increased, underlining the importance of integrin activation for early FN fibrillogenesis. FN fibrillogenesis visualized by time-lapse AFM thus provides new structural and mechanistic insight into initial steps of cell-driven FN fibrillogenesis. PMID- 26371082 TI - Transcriptome-Wide Differential Gene Expression in Bicyclus anynana Butterflies: Female Vision-Related Genes Are More Plastic. AB - Vision is energetically costly to maintain. Consequently, over time many cave adapted species downregulate the expression of vision genes or even lose their eyes and associated eye genes entirely. Alternatively, organisms that live in fluctuating environments, with different requirements for vision at different times, may evolve phenotypic plasticity for expression of vision genes. Here, we use a global transcriptomic and candidate gene approach to compare gene expression in the heads of a polyphenic butterfly. Bicyclus anynana have two seasonal forms that display sexual dimorphism and plasticity in eye morphology, and female-specific plasticity in opsin gene expression. Nonchoosy dry season females downregulate opsin expression, consistent with the high physiological cost of vision. To identify other genes associated with sexually dimorphic and seasonally plastic differences in vision, we analyzed RNA-sequencing data from whole head tissues. We identified two eye development genes (klarsicht and warts homologs) and an eye pigment biosynthesis gene (henna) differentially expressed between seasonal forms. By comparing sex-specific expression across seasonal forms, we found that klarsicht, warts, henna, and another eye development gene (domeless) were plastic in a female-specific manner. In a male-only analysis, white (w) was differentially expressed between seasonal forms. Reverse transcription polymerase chain reaction confirmed that warts and white are expressed in eyes only, whereas klarsicht, henna and domeless are expressed in both eyes and brain. We find that differential expression of eye development and eye pigment genes is associated with divergent eye phenotypes in B. anynana seasonal forms, and that there is a larger effect of season on female vision related genes. PMID- 26371080 TI - The double trouble of metabolic diseases: the diabetes-cancer link. AB - The recent recognition of the clinical association between type 2 diabetes (T2D) and several types of human cancer has been further highlighted by reports of antidiabetic drugs treating or promoting cancer. At the cellular level, a plethora of molecules operating within distinct signaling pathways suggests cross talk between the multiple pathways at the interface of the diabetes-cancer link. Additionally, a growing body of emerging evidence implicates homeostatic pathways that may become imbalanced during the pathogenesis of T2D or cancer or that become chronically deregulated by prolonged drug administration, leading to the development of cancer in diabetes and vice versa. This notion underscores the importance of combining clinical and basic mechanistic studies not only to unravel mechanisms of disease development but also to understand mechanisms of drug action. In turn, this may help the development of personalized strategies in which drug doses and administration durations are tailored to individual cases at different stages of the disease progression to achieve more efficacious treatments that undermine the diabetes-cancer association. PMID- 26371083 TI - CALIBRATION OF A WHOLE BODY COUNTER FOR 241Am WITH THE LLNL CHEST PHANTOM. AB - An occupational incorporation event occurred at the Radioactive Waste Treatment and Disposal Facility in December 2013 at Puspokszilagy, Hungary. Internal contamination due to (241)Am was discovered by a regular routine whole body counting measurement at the Centre for Energy Research, Hungarian Academy of Sciences. After that, a whole body counter was calibrated for an organ counting geometry. For preliminary calibration, a home-made MIX-D chest phantom was applied simulating uniform lung activity distribution by (241)Am point sources located in different positions within the lung volume of the phantom. In order to carry out a more precise calibration, a Lawrence Livermore National Laboratory (LLNL) chest phantom was provided by the International Atomic Energy Agency. For counting efficiency over the lungs, values of 0.46+/-0.19 and 0.55+/-0.07 cps kBq(-1) were obtained for the MIX-D and the LLNL phantom, respectively; thus, the results are in good agreement. PMID- 26371084 TI - MONITORING DOSE-LENGTH PRODUCT IN COMPUTED TOMOGRAPHY OF THE CHEST CONSIDERING SEX AND BODY WEIGHT. AB - Dose-length product (DLP) is widely used as an indicator of the radiation dose in computed tomography. The aim of this study was to investigate the significance of sex and body weight in DLP-based monitoring of the radiation dose. Eight hundred computed tomographies of the chest performed using four different scanners were analysed. The DLP was compared with body weight by linear regression in men and women separately. The DLP was positively correlated with body weight, and dependence on sex and weight differed among scanners. Standard DLP values adjusted for sex and weight facilitated interscanner comparison of the radiation dose and its dependence on sex and weight. Adjusting the DLP for sex and weight allowed one to identify examinations with possibly excessive doses independently of weight. Monitoring the DLP in relation to sex and body weight appears to aid detailed comparison of the radiation dose among imaging protocols and scanners and daily observations to find unexpected variance. PMID- 26371085 TI - DOSE MEASUREMENTS IN THE STRAY FIELD OF A GE OPTIMA CT660. AB - Statistics show how important computed tomography (CT) dosimetry has become. In order to estimate the dose distribution in the CT scan room during an examination, measurements of the ambient dose equivalent H*(10) have been performed. The primary aim of this study is the radiation protection of the staff and not the determination of the dose to the patient or in the primary beam. Therefore, the dose outside the primary beam, i.e. in the scattered field of the Physikalisch-Technische Bundesanstalt's GE Optima CT660, is of importance. The results of the dose measurements are analysed in dependence on the settings of the X-ray tube voltage, the collimator width and (with and without) the bow-tie filter of the CT scanner. For the radiation protection measurements, ionisation chambers have been used. Additionally, the influence of the patient on the radiation field and, therefore, on the dose is simulated by using an Alderson body phantom. PMID- 26371086 TI - The use of single photon emission computed tomography/computed tomography to differentiate between pain arising from trapeziometacarpal joint and scaphotrapeziotrapezoid joint osteoarthritis. PMID- 26371087 TI - Deaf Victims' Experiences With Intimate Partner Violence: The Need for Integration and Innovation. AB - While in recent years, intimate partner violence (IPV) has attracted considerable research attention, the experiences of IPV affecting the Deaf community have been understudied. As a linguistic and cultural minority, Deaf victims of IPV encounter significant barriers in accessing information and services designed to address the medical and legal consequences of victimization. The number of Deaf Americans who communicate via American Sign Language (ASL) may well exceed a half million, yet little is known about Deaf IPV victims' experiences and the characteristics of persons who perpetrate IPV with ASL users. This study addressed both topics. The current study is based on interviews in ASL with 14 Deaf IPV victims (participants). We explored: the types of abuse participants experienced; characteristics of victims and perpetrators; participants' help seeking behaviors; and the availability, use, and helpfulness of various resources. These findings were compared to what is known about IPV in the hearing community. Our findings include that lack of information regarding IPV and lack of access to specialized IPV services were pervasive problems affecting Deaf victims. For some victims, the close-knit nature of the Deaf community was a barrier for discussing IPV and accessing information and support. It was common for Deaf victims to receive services or information about IPV from providers who were not IPV specialists. Communication abuse was prevalent in our study. The nature of communication abuse is unique for Deaf victims compared to hearing victims. PMID- 26371088 TI - Sexual Attitudes Moderate the Effects of Alcohol Intoxication on Women's Risk Judgments. AB - This study evaluated the effects of alcohol intoxication, sexual attitudes, and sexual victimization history on the cognitive processes underlying undergraduate women's risk judgments. Participants were 116 unmarried, undergraduate women between the ages of 21 and 29. The sample was diverse ethnically and composed primarily of heterosexual women. Stimuli were written vignettes describing social situations that varied on dimensions of sexual victimization risk and potential impact on women's popularity. Participants were assigned randomly to an alcohol or a no-alcohol condition, and completed an explicit classification task in which they rated how risky each situation was in terms of their having an unwanted sexual experience. They then completed the Sexual Experiences Survey (SES) and the Sociosexuality Scale (SS); SES responses were used to quantify the severity of victimization experiences, and SS responses were used to measure endorsement of positive attitudes toward casual, impersonal sex. Although there was no main effect for condition, higher sociosexuality predicted use of higher thresholds for judging situations as risky. Importantly, sociosexuality interacted with condition such that higher sociosexuality predicted lower sensitivity to risk information in the alcohol condition but not in the no-alcohol condition. More severe victimization history predicted increased use of popularity impactwhen judging risk. This study emphasizes the importance of identifying specific cognitive processes affected by alcohol that may explain why women have difficulty processing contextual cues signaling risk in social situations. It demonstrates also the relevance of examining individual difference factors that may exacerbate the relationship between intoxication and cognitive processing of risk-relevant information. PMID- 26371089 TI - The first thoracic triumvirate. PMID- 26371090 TI - Correction. PMID- 26371092 TI - Art of medicine. PMID- 26371094 TI - The lost competency: CanMEDS-Family Medicine and prognosis. PMID- 26371095 TI - Manifesto for family medicine educational research. PMID- 26371097 TI - Alopecia areata: Part 1: pathogenesis, diagnosis, and prognosis. AB - OBJECTIVE: To provide family physicians with a background understanding of the epidemiology, pathogenesis, histology, and clinical approach to the diagnosis of alopecia areata (AA). SOURCES OF INFORMATION: PubMed was searched for relevant articles regarding the pathogenesis, diagnosis, and prognosis of AA. MAIN MESSAGE: Alopecia areata is a form of autoimmune hair loss with a lifetime prevalence of approximately 2%. A personal or family history of concomitant autoimmune disorders, such as vitiligo or thyroid disease, might be noted in a small subset of patients. Diagnosis can often be made clinically, based on the characteristic nonscarring, circular areas of hair loss, with small "exclamation mark" hairs at the periphery in those with early stages of the condition. The diagnosis of more complex cases or unusual presentations can be facilitated by biopsy and histologic examination. The prognosis varies widely, and poor outcomes are associated with an early age of onset, extensive loss, the ophiasis variant, nail changes, a family history, or comorbid autoimmune disorders. CONCLUSION: Alopecia areata is an autoimmune form of hair loss seen regularly in primary care. Family physicians are well placed to identify AA, characterize the severity of disease, and form an appropriate differential diagnosis. Further, they are able educate their patients about the clinical course of AA, as well as the overall prognosis, depending on the patient subtype. PMID- 26371098 TI - Alopecia areata: Part 2: treatment. AB - OBJECTIVE: To provide family physicians with a background understanding of the therapeutic regimens and treatment outcomes for alopecia areata (AA), as well as to help identify those patients for whom dermatologist referral might be required. SOURCES OF INFORMATION: PubMed was searched for relevant articles regarding the treatment of AA. MAIN MESSAGE: Alopecia areata is a form of autoimmune hair loss affecting both children and adults. While there is no associated mortality with the disease, morbidity from the psychological effects of hair loss can be devastating. Upon identification of AA and the disease subtype, an appropriate therapeutic regimen can be instituted to help halt hair loss or possibly initiate hair regrowth. First-line treatment involves intralesional triamcinolone with topical steroids or minoxidil or both. Primary care physicians can safely prescribe and institute these treatments. More advanced or refractory cases might require oral immunosuppressants, topical diphenylcyclopropenone, or topical anthralin. Eyelash loss can be treated with prostaglandin analogues. Those with extensive loss might choose camouflaging options or a hair prosthesis. It is important to monitor for psychiatric disorders owing to the profound psychological effects of hair loss. CONCLUSION: Family physicians will encounter many patients experiencing hair loss. Recognition of AA and an understanding of the underlying disease process will allow an appropriate therapeutic regimen to be instituted. More advanced or refractory cases need to be identified, allowing for an appropriate dermatologist referral when necessary. PMID- 26371099 TI - Adult pneumococcal immunization. PMID- 26371100 TI - Omega-3 and dyslexia: Uncertain connection. AB - QUESTION: In light of the increase in the number of school-aged children diagnosed with dyslexia, what is the role of omega-3 supplements in the management of this condition? ANSWER: Dyslexia is the most common learning disability and is known to have multifactorial causes. Recent evidence suggests that there is a connection between defects in highly unsaturated fatty acid metabolism and neurodevelopmental disorders such as dyslexia. While the benefit of omega-3 supplementation for children with dyslexia has been studied, evidence remains limited. Unified diagnostic criteria for dyslexia, objective measures of fatty acid deficiency, and close monitoring of dietary intake are some of the factors that would improve the quality of research in the field. PMID- 26371101 TI - Lipoid pneumonia: An unusual and preventable illness in elderly patients. PMID- 26371102 TI - Evaluating the Epley maneuver. PMID- 26371103 TI - A family portrait. PMID- 26371104 TI - Debbie Dooler MD CCFP. PMID- 26371105 TI - Why most randomized controlled trials are irrelevant: And why yours will not be. PMID- 26371106 TI - Good neighbours. PMID- 26371109 TI - Physician practice improvement. PMID- 26371111 TI - Tobacco imagery in video games: ratings and gamer recall. AB - OBJECTIVE: To assess whether tobacco content found in video games was appropriately labelled for tobacco-related content by the Entertainment and Software Ratings Board (ESRB). METHODS: Sixty-five gamer participants (self identified age range 13-50) were interviewed in-person (n=25) or online (n=40) and asked (A) to list favourite games and (B) to name games that they could recall containing tobacco content. The ESRB database was searched for all games mentioned to ascertain whether they had been assigned tobacco-related content descriptors. Games were independently assessed for tobacco content by examining user-created game wiki sites and watching YouTube videos of gameplay. Games with tobacco-related ESRB content descriptors and/or with tobacco imagery verified by researchers were considered to contain tobacco content. Games identified by participants as including tobacco but lacking verifiable tobacco content were treated as not containing tobacco content. RESULTS: Participants recalled playing 140 unique games, of which 118 were listed in the ESRB database. Participants explicitly recalled tobacco content in 31% (37/118) of the games, of which 94% (35/37) included independently verified tobacco content. Only 8% (9/118) of the games had received ESRB tobacco-related content descriptors, but researchers verified that 42% (50/118) contained such content; 42% (49/118) of games were rated 'M' for mature (content deemed appropriate for ages 17+). Of these, 76% (37/49) contained verified tobacco content; however, only 4% (2/49) received ESRB tobacco-related content descriptors. CONCLUSIONS: Gamers are exposed to tobacco imagery in many video games. The ESRB is not a reliable source for determining whether video games contain tobacco imagery. PMID- 26371112 TI - Attitudes to smoke-free outdoor regulations in the USA and Canada: a review of 89 surveys. AB - OBJECTIVE: To review the published survey data on public support for smoke-free outdoor regulations in the USA and Canada (two countries at the forefront of such policies). DATA SOURCES AND STUDY SELECTION: We searched for English language articles and reports using Medline, Google Scholar and Google for the period to December 2014. We retained population-based surveys of the adult general population in jurisdictions in the USA and Canada, with a minimum survey sample of 500. DATA EXTRACTION: The analysis focused on assessing levels and trends in public support for different types of places and also explored how support varied between population groups. RESULTS: Relevant data were found from 89 cross sectional surveys between 1993 and 2014. Support for smoke-free regulations in outdoor places tended to be highest for smoke-free school grounds (range: 57-95%) playgrounds (89-91%), and building entrances (45-89%) and lowest for smoke-free outdoor workplaces (12-46%) and sidewalks (31-49%). Support was lower among smokers, though for some types of places there was majority smoker support (eg, school grounds with at least 77% support in US state surveys after 2004). Trend data involving the same questions and the same surveyed populations suggested increased general public and smoker support for smoke-free regulations over time (eg, from 67% to 78% during 2002-2008 for smoke-free school grounds in the USA). Higher support was typically seen from women and some ethnic groups (eg, African Americans). CONCLUSIONS: Outdoor smoke-free regulations can achieve majority public support, including from smokers. PMID- 26371113 TI - Clinical outcomes in patients with atrial fibrillation according to sex during anticoagulation with apixaban or warfarin: a secondary analysis of a randomized controlled trial. AB - AIM: To assess clinical outcomes, efficacy, and safety according to sex during anticoagulation with apixaban compared with warfarin in patients with atrial fibrillation. METHODS AND RESULTS: Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) was a randomized, double blind, placebo-controlled, multicentre trial that included 11 785 (64.7%) men and 6416 (35.3%) women with atrial fibrillation or flutter randomized to receive either warfarin or apixaban. The primary efficacy endpoint was stroke or systemic embolism; secondary efficacy endpoints were death from any cause and cardiovascular death. The primary safety endpoint was major bleeding; secondary safety endpoints were a composite of major bleeding and non-major clinically relevant bleeding. The risk of stroke or systemic embolism was similar in women vs. men [adjusted hazard ratio (adjHR): 0.91; 95% confidence interval (CI): 0.74 1.12; P = 0.38]. However, among patients with history of stroke or transient ischaemic attack, women had a lower risk of recurrent stroke compared with men (adjHR: 0.70; 95% CI: 0.50-0.97; P = 0.036). Women also had a lower risk of all cause death (adjHR: 0.63; 95% CI: 0.55-0.73; P < 0.0001) and cardiovascular death (adjHR: 0.62; 95% CI: 0.51-0.75; P < 0.0001), and a trend towards less major bleeding (adjHR: 0.86; 95% CI: 0.74-1.01; P = 0.066) and major or non-major clinically relevant bleeding (adjHR: 0.89; 95% CI: 0.80-1.00; P = 0.049). The efficacy and safety benefits of apixaban compared with warfarin were consistent regardless of sex. CONCLUSION: In the ARISTOTLE trial, women had a similar rate of stroke or systemic embolism but a lower risk of mortality and less clinically relevant bleeding than men. The efficacy and safety benefits of apixaban compared with warfarin were consistent in men and women. TRIAL REGISTRATION: ARISTOTLE ClinicalTrials.gov number, NCT00412984. PMID- 26371114 TI - The role of obesity in atrial fibrillation. AB - Atrial fibrillation (AF) is commonly associated with overweight and obesity. Both conditions have been identified as major global epidemics associated with increased mortality and morbidity. Overweight populations have higher incidence, prevalence, severity, and progression of AF compared with their normal weight counterparts. Additionally, weight change appears to accompany alteration of arrhythmia profile, raising overweight, and obesity as potential targets for intervention. Recent clinical data confirm hypothesis drawn from epidemiological studies that durable weight reduction strategies facilitate effective management of AF. Stable weight loss decreases AF burden and AF recurrence following treatment. Structural remodelling in response to weight loss suggests that reverse remodelling of the AF substrate mediates improvement of arrhythmia profile. Obesity often co-exists with multiple AF risk factors that improve in response to weight loss, making a consolidated approach of weight loss and AF risk factor management preferable. However, weight loss for AF remains in its infancy, and its broad adoption as a management strategy for AF remains to be defined. PMID- 26371115 TI - Lean body mass and risk of incident atrial fibrillation in post-menopausal women. AB - AIMS: High body mass index (BMI) is a risk factor for atrial fibrillation (AF). The aim of this study was to determine whether lean body mass (LBM) predicts AF. METHODS AND RESULTS: The Women's Health Initiative is a study of post-menopausal women aged 50-79 enrolled at 40 US centres from 1994 to 1998. A subset of 11 393 participants at three centres underwent dual-energy X-ray absorptiometry. Baseline demographics and clinical histories were recorded. Incident AF was identified using hospitalization records and diagnostic codes from Medicare claims. A multivariable Cox hazard regression model adjusted for demographic and clinical risk factors was used to evaluate associations between components of body composition and AF risk. After exclusion for prevalent AF or incomplete data, 8832 participants with an average age of 63.3 years remained for analysis. Over the 11.6 years of average follow-up time, 1035 women developed incident AF. After covariate adjustment, all measures of LBM were independently associated with higher rates of AF: total LBM [hazard ratio (HR) 1.24 per 5 kg increase, 95% confidence intervals (CI) 1.14-1.34], central LBM (HR 1.51 per 5 kg increase, 95% CI 1.31-1.74), and peripheral LBM (HR 1.39 per 5 kg increase, 95% CI 1.19-1.63). The association between total LBM and AF remained significant after adjustment for total fat mass (HR 1.22 per 5 kg increase, 95% CI 1.13-1.31). CONCLUSION: Greater LBM is a strong independent risk factor for AF. After adjusting for obesity-related risk factors, the risk of AF conferred by higher BMI is primarily driven by the association between LBM and AF. PMID- 26371116 TI - Improving survival after out-of-hospital cardiac arrest requires new tools. PMID- 26371117 TI - Suicide loss, changes in medical care utilization, and hospitalization for cardiovascular disease and diabetes mellitus. AB - AIMS: The impact of suicide loss on family members' cardiometabolic health has little been evaluated in middle-aged and elderly people. We investigated the effect of suicide loss on risks for cardiovascular disease (CVD) and diabetes mellitus (DM) in suicide completers' family members using a national representative comparison group. METHODS AND RESULTS: The study subjects were 4253 family members of suicide completers and 9467 non-bereaved family members of individuals who were age and gender matched with the suicide completers in the Republic of Korea. National health insurance data were used to identify medical care utilization during the year before and after a suicide loss. A recurrent events survival analysis was performed to estimate the hazard ratios (HRs) of hospitalizations for CVD, DM, or psychiatric disorders, after adjusting for age, residence, and socioeconomic status. Among subjects without a past history of CVD, DM, or psychiatric disorders, the increased risks of recurrent hospitalizations were observed for CVD [HR 1.343, 95% confidence interval (CI) 1.001-1.800 in men; HR 1.240, 95% CI 1.025-1.500 in women] and DM (HR 2.238, 95% CI 1.379-3.362 in men; HR 1.786, 95% CI 1.263-2.527 in women). In subjects with a past history of CVD, DM, or psychiatric disorders, the number of medical care visits decreased after a suicide loss, and suicide completers' family members showed lower rates of hospitalization for CVD and DM than the comparison group. CONCLUSION: Compared with non-bereaved family members, suicide completers' family members without a past history of CVD, DM, or psychiatric disorder showed a high risk of hospitalization for those conditions. PMID- 26371118 TI - Sudden death in structurally normal heart: we have learned a lot, but still a long way to go. PMID- 26371119 TI - (A)Historical science. AB - In contrast to many other human endeavors, science pays little attention to its history. Fundamental scientific discoveries are often considered to be timeless and independent of how they were made. Science and the history of science are regarded as independent academic disciplines. Although most scientists are aware of great discoveries in their fields and their association with the names of individual scientists, few know the detailed stories behind the discoveries. Indeed, the history of scientific discovery is sometimes recorded only in informal accounts that may be inaccurate or biased for self-serving reasons. Scientific papers are generally written in a formulaic style that bears no relationship to the actual process of discovery. Here we examine why scientists should care more about the history of science. A better understanding of history can illuminate social influences on the scientific process, allow scientists to learn from previous errors, and provide a greater appreciation for the importance of serendipity in scientific discovery. Moreover, history can help to assign credit where it is due and call attention to evolving ethical standards in science. History can make science better. PMID- 26371120 TI - Periodontal pathogens invade gingiva and aortic adventitia and elicit inflammasome activation in alphavbeta6 integrin-deficient mice. AB - The American Heart Association supports an association between periodontal diseases and atherosclerosis but not a causal association. This study explores the use of the integrin beta6(-/-) mouse model to study the causality. We investigated the ability of a polymicrobial consortium of Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia, and Fusobacterium nucleatum to colonize the periodontium and induce local and systemic inflammatory responses. Polymicrobially infected Itgbeta6(-/-) mice demonstrate greater susceptibility to gingival colonization/infection, with severe gingival inflammation, apical migration of the junctional epithelium, periodontal pocket formation, alveolar bone resorption, osteoclast activation, bacterial invasion of the gingiva, a greater propensity for the bacteria to disseminate hematogenously, and a strong splenic T cell cytokine response. Levels of atherosclerosis risk factors, including serum nitric oxide, oxidized low-density lipoprotein, serum amyloid A, and lipid peroxidation, were significantly altered by polybacterial infection, demonstrating an enhanced potential for atherosclerotic plaque progression. Aortic gene expression revealed significant alterations in specific Toll-like receptor (TLR) and nucleotide-binding domain- and leucine-rich-repeat containing receptor (NLR) pathway genes in response to periodontal bacterial infection. Histomorphometry of the aorta demonstrated larger atherosclerotic plaques in Itgbeta6(-/-) mice than in wild-type (WT) mice but no significant difference in atherosclerotic plaque size between mice with polybacterial infection and mice with sham infection. Fluorescence in situ hybridization demonstrated active invasion of the aortic adventitial layer by P. gingivalis. Our observations suggest that polybacterial infection elicits distinct aortic TLR and inflammasome signaling and significantly increases local aortic oxidative stress. These results are the first to demonstrate the mechanism of the host aortic inflammatory response induced by polymicrobial infection with well characterized periodontal pathogens. PMID- 26371121 TI - Neither classical nor alternative macrophage activation is required for Pneumocystis clearance during immune reconstitution inflammatory syndrome. AB - Pneumocystis is a respiratory fungal pathogen that causes pneumonia (Pneumocystis pneumonia [PcP]) in immunocompromised patients. Alveolar macrophages are critical effectors for CD4(+) T cell-dependent clearance of Pneumocystis, and previous studies found that alternative macrophage activation accelerates fungal clearance during PcP-related immune reconstitution inflammatory syndrome (IRIS). However, the requirement for either classically or alternatively activated macrophages for Pneumocystis clearance has not been determined. Therefore, RAG2(-/-) mice lacking either the interferon gamma (IFN-gamma) receptor (IFN-gammaR) or interleukin 4 receptor alpha (IL-4Ralpha) were infected with Pneumocystis. These mice were then immune reconstituted with wild-type lymphocytes to preserve the normal T helper response while preventing downstream effects of Th1 or Th2 effector cytokines on macrophage polarization. As expected, RAG2(-/-) mice developed severe disease but effectively cleared Pneumocystis and resolved IRIS. Neither RAG/IFN-gammaR(-/-) nor RAG/IL-4Ralpha(-/-) mice displayed impaired Pneumocystis clearance. However, RAG/IFN-gammaR(-/-) mice developed a dysregulated immune response, with exacerbated IRIS and greater pulmonary function deficits than those in RAG2 and RAG/IL-4Ralpha(-/-) mice. RAG/IFN-gammaR(-/-) mice had elevated numbers of lung CD4(+) T cells, neutrophils, eosinophils, and NK cells but severely depressed numbers of lung CD8(+) T suppressor cells. Impaired lung CD8(+) T cell responses in RAG/IFN-gammaR(-/-) mice were associated with elevated lung IFN-gamma levels, and neutralization of IFN-gamma restored the CD8 response. These data demonstrate that restricting the ability of macrophages to polarize in response to Th1 or Th2 cytokines does not impair Pneumocystis clearance. However, a cell type-specific IFN-gamma/IFN-gammaR-dependent mechanism regulates CD8(+) T suppressor cell recruitment, limits immunopathogenesis, preserves lung function, and enhances the resolution of PcP-related IRIS. PMID- 26371122 TI - Immunomodulatory metabolites released by the frog-killing fungus Batrachochytrium dendrobatidis. AB - Batrachochytrium dendrobatidis is a fungal pathogen in the phylum Chytridiomycota that causes the skin disease chytridiomycosis. Chytridiomycosis is considered an emerging infectious disease linked to worldwide amphibian declines and extinctions. Although amphibians have well-developed immune defenses, clearance of this pathogen from the skin is often impaired. Previously, we showed that the adaptive immune system is involved in the control of the pathogen, but B. dendrobatidis releases factors that inhibit in vitro and in vivo lymphocyte responses and induce lymphocyte apoptosis. Little is known about the nature of the inhibitory factors released by this fungus. Here, we describe the isolation and characterization of three fungal metabolites produced by B. dendrobatidis but not by the closely related nonpathogenic chytrid Homolaphlyctis polyrhiza. These metabolites are methylthioadenosine (MTA), tryptophan, and an oxidized product of tryptophan, kynurenine (Kyn). Independently, both MTA and Kyn inhibit the survival and proliferation of amphibian lymphocytes and the Jurkat human T cell leukemia cell line. However, working together, they become effective at much lower concentrations. We hypothesize that B. dendrobatidis can adapt its metabolism to release products that alter the local environment in the skin to inhibit immunity and enhance the survival of the pathogen. PMID- 26371123 TI - Campylobacter jejuni increases flagellar expression and adhesion of noninvasive Escherichia coli: effects on enterocytic Toll-like receptor 4 and CXCL-8 expression. AB - Campylobacter jejuni is the most common cause of bacterium-induced gastroenteritis, and while typically self-limiting, C. jejuni infections are associated with postinfectious intestinal disorders, including flares in patients with inflammatory bowel disease and postinfectious irritable bowel syndrome (PI IBS), via mechanisms that remain obscure. Based on the hypothesis that acute campylobacteriosis may cause pathogenic microbiota dysbiosis, we investigated whether C. jejuni may activate dormant virulence genes in noninvasive Escherichia coli and examined the epithelial pathophysiological consequences of these alterations. Microarray and quantitative real-time PCR analyses revealed that E. coli adhesin, flagellum, and hemolysin gene expression were increased when E. coli was exposed to C. jejuni-conditioned medium. Increased development of bacterial flagella upon exposure to live C. jejuni or C. jejuni-conditioned medium was observed under transmission electron microscopy. Atomic force microscopy demonstrated that the forces of bacterial adhesion to colonic T84 enterocytes, and the work required to rupture this adhesion, were significantly increased in E. coli exposed to C. jejuni-conditioned media. Finally, C. jejuni modified E. coli disrupted TLR4 gene expression and induced proinflammatory CXCL 8 gene expression in colonic enterocytes. Together, these data suggest that exposure to live C. jejuni, and/or to its secretory-excretory products, may activate latent virulence genes in noninvasive E. coli and that these alterations may directly trigger proinflammatory signaling in intestinal epithelia. These observations shed new light on mechanisms that may contribute, at least in part, to postcampylobacteriosis inflammatory disorders. PMID- 26371124 TI - Toll-like receptor 9 signaling in dendritic cells regulates neutrophil recruitment to inflammatory foci following Leishmania infantum infection. AB - Leishmania infantum is a protozoan parasite that causes visceral leishmaniasis (VL). This infection triggers dendritic cell (DC) activation through the recognition of microbial products by Toll-like receptors (TLRs). Among the TLRs, TLR9 is required for DC activation by different Leishmania species. We demonstrated that TLR9 is upregulated in vitro and in vivo during infection. We show that C57BL/6 mice deficient in TLR9 expression (TLR9(-/-) mice) are more susceptible to infection and display higher parasite numbers in the spleen and liver. The increased susceptibility of TLR9(-/-) mice was due to the impaired recruitment of neutrophils to the infection foci associated with reduced levels of neutrophil chemoattractants released by DCs in the target organs. Moreover, both Th1 and Th17 cells were also committed in TLR9(-/-) mice. TLR9-dependent neutrophil recruitment is mediated via the MyD88 signaling pathway but is TIR domain-containing adapter-inducing interferon beta (TRIF) independent. Furthermore, L. infantum failed to activate both plasmacytoid and myeloid DCs from TLR9(-/-) mice, which presented reduced surface costimulatory molecule expression and chemokine release. Interestingly, neutrophil chemotaxis was affected both in vitro and in vivo when DCs were derived from TLR9(-/-) mice. Our results suggest that TLR9 plays a critical role in neutrophil recruitment during the protective response against L. infantum infection that could be associated with DC activation. PMID- 26371125 TI - The Cnes2 locus on mouse chromosome 17 regulates host defense against cryptococcal infection through pleiotropic effects on host immunity. AB - The genetic basis of natural susceptibility to progressive Cryptococcus neoformans infection is not well understood. Using C57BL/6 and CBA/J inbred mice, we previously identified three chromosomal regions associated with C. neoformans susceptibility (Cnes1, Cnes2, and Cnes3). To validate and characterize the role of Cnes2 during the host response, we constructed a congenic strain on the C57BL/6 background (B6.CBA-Cnes2). Phenotypic analysis of B6.CBA-Cnes2 mice 35 days after C. neoformans infection showed a significant reduction of fungal burden in the lungs and spleen with higher pulmonary expression of gamma interferon (IFN-gamma) and interleukin-12 (IL-12), lower expression of IL-4, IL 5, and IL-13, and an absence of airway epithelial mucus production compared to that in C57BL/6 mice. Multiparameter flow cytometry of infected lungs also showed a significantly higher number of neutrophils, exudate macrophages, CD11b(+) dendritic cells, and CD4(+) cells in B6.CBA-Cnes2 than in C57BL/6 mice. The activation state of recruited macrophages and dendritic cells was also significantly increased in B6.CBA-Cnes2 mice. Taken together, these findings demonstrate that the Cnes2 interval is a potent regulator of host defense, immune responsiveness, and differential Th1/Th2 polarization following C. neoformans infection. PMID- 26371126 TI - Maternal vaccination with a fimbrial tip adhesin and passive protection of neonatal mice against lethal human enterotoxigenic Escherichia coli challenge. AB - Globally, enterotoxigenic Escherichia coli (ETEC) is a leading cause of childhood and travelers' diarrhea, for which an effective vaccine is needed. Prevalent intestinal colonization factors (CFs) such as CFA/I fimbriae and heat-labile enterotoxin (LT) are important virulence factors and protective antigens. We tested the hypothesis that donor strand-complemented CfaE (dscCfaE), a stabilized form of the CFA/I fimbrial tip adhesin, is a protective antigen, using a lethal neonatal mouse ETEC challenge model and passive dam vaccination. For CFA/I-ETEC strain H10407, which has been extensively studied in volunteers, an inoculum of 2 * 10(7) bacteria resulted in 50% lethal doses (LD50) in neonatal DBA/2 mice. Vaccination of female DBA/2 mice with CFA/I fimbriae or dscCfaE, each given with a genetically attenuated LT adjuvant (LTK63) by intranasal or orogastric delivery, induced high antigen-specific serum IgG and fecal IgA titers and detectable milk IgA responses. Neonates born to and suckled by dams antenatally vaccinated with each of these four regimens showed 78 to 93% survival after a 20* LD50 challenge with H10407, compared to 100% mortality in pups from dams vaccinated with sham vaccine or LTK63 only. Crossover experiments showed that high pup survival rates after ETEC challenge were associated with suckling but not birthing from vaccinated dams, suggesting that vaccine-specific milk antibodies are protective. In corroboration, preincubation of the ETEC inoculum with antiadhesin and antifimbrial bovine colostral antibodies conferred a dose dependent increase in pup survival after challenge. These findings indicate that the dscCfaE fimbrial tip adhesin serves as a protective passive vaccine antigen in this small animal model and merits further evaluation. PMID- 26371127 TI - Pulmonary immunostimulation with MALP-2 in influenza virus-infected mice increases survival after pneumococcal superinfection. AB - Pulmonary infection with influenza virus is frequently complicated by bacterial superinfection, with Streptococcus pneumoniae being the most prevalent causal pathogen and hence often associated with high morbidity and mortality rates. Local immunosuppression due to pulmonary influenza virus infection has been identified as a major cause of the pathogenesis of secondary bacterial lung infection. Thus, specific local stimulation of the pulmonary innate immune system in subjects with influenza virus infection might improve the host defense against secondary bacterial pathogens. In the present study, we examined the effect of pulmonary immunostimulation with Toll-like receptor 2 (TLR-2)-stimulating macrophage-activating lipopeptide 2 (MALP-2) in influenza A virus (IAV)-infected mice on the course of subsequent pneumococcal superinfection. Female C57BL/6N mice infected with IAV were treated with MALP-2 on day 5 and challenged with S. pneumoniae on day 6. Intratracheal MALP-2 application increased proinflammatory cytokine and chemokine release and enhanced the recruitment of leukocytes, mainly neutrophils, into the alveolar space of IAV-infected mice, without detectable systemic side effects. Local pulmonary instillation of MALP-2 in IAV-infected mice 24 h before transnasal pneumococcal infection considerably reduced the bacterial number in the lung tissue without inducing exaggerated inflammation. The pulmonary viral load was not altered by MALP-2. Clinically, MALP-2 treatment of IAV-infected mice increased survival rates and reduced hypothermia and body weight loss after pneumococcal superinfection compared to those of untreated coinfected mice. In conclusion, local immunostimulation with MALP-2 in influenza virus-infected mice improved pulmonary bacterial elimination and increased survival after subsequent pneumococcal superinfection. PMID- 26371128 TI - Interspecies variations in Bordetella catecholamine receptor gene regulation and function. AB - Bordetella bronchiseptica can use catecholamines to obtain iron from transferrin and lactoferrin via uptake pathways involving the BfrA, BfrD, and BfrE outer membrane receptor proteins, and although Bordetella pertussis has the bfrD and bfrE genes, the role of these genes in iron uptake has not been demonstrated. In this study, the bfrD and bfrE genes of B. pertussis were shown to be functional in B. bronchiseptica, but neither B. bronchiseptica bfrD nor bfrE imparted catecholamine utilization to B. pertussis. Gene fusion analyses found that expression of B. bronchiseptica bfrA was increased during iron starvation, as is common for iron receptor genes, but that expression of the bfrD and bfrE genes of both species was decreased during iron limitation. As shown previously for B. pertussis, bfrD expression in B. bronchiseptica was also dependent on the BvgAS virulence regulatory system; however, in contrast to the case in B. pertussis, the known modulators nicotinic acid and sulfate, which silence Bvg-activated genes, did not silence expression of bfrD in B. bronchiseptica. Further studies using a B. bronchiseptica bvgAS mutant expressing the B. pertussis bvgAS genes revealed that the interspecies differences in bfrD modulation are partly due to BvgAS differences. Mouse respiratory infection experiments determined that catecholamine utilization contributes to the in vivo fitness of B. bronchiseptica and B. pertussis. Additional evidence of the in vivo importance of the B. pertussis receptors was obtained from serologic studies demonstrating pertussis patient serum reactivity with the B. pertussis BfrD and BfrE proteins. PMID- 26371129 TI - Host contributions to construction of three device-associated Candida albicans biofilms. AB - Among the most fascinating virulence attributes of Candida is the ability to transition to a biofilm lifestyle. As a biofilm, Candida cells adhere to a surface, such as a vascular catheter, and become encased in an extracellular matrix. During this mode of growth, Candida resists the normal immune response, often causing devastating disease. Based on scanning electron microscopy images, we hypothesized that host cells and proteins become incorporated into clinical biofilms. As a means to gain an understanding of these host-biofilm interactions, we explored biofilm-associated host components by using microscopy and liquid chromatography-mass spectrometry. Here we characterize the host proteins associated with several in vivo rat Candida albicans biofilms, including those from vascular catheter, denture, and urinary catheter models as well as uninfected devices. A conserved group of 14 host proteins were found to be more abundant during infection at each of the niches. The host proteins were leukocyte and erythrocyte associated and included proteins involved in inflammation, such as C-reactive protein, myeloperoxidase, and alarmin S100-A9. A group of 59 proteins were associated with both infected and uninfected devices, and these included matricellular and inflammatory proteins. In addition, site-specific proteins were identified, such as amylase in association with the denture device. Cellular analysis revealed neutrophils as the predominant leukocytes associating with biofilms. These experiments demonstrate that host cells and proteins are key components of in vivo Candida biofilms, likely with one subset associating with the device and another being recruited by the proliferating biofilm. PMID- 26371130 TI - The fibronectin-binding protein Fnm contributes to adherence to extracellular matrix components and virulence of Enterococcus faecium. AB - The interaction between bacteria and fibronectin is believed to play an important role in the pathogenicity of clinically important Gram-positive cocci. In the present study, we identified a gene encoding a predicted fibronectin-binding protein of Enterococcus faecium (fnm), a homologue of Streptococcus pneumoniae pavA, in the genomes of E. faecium strain TX82 and all other sequenced E. faecium isolates. Full-length recombinant Fnm from strain TX82 bound to immobilized fibronectin in a concentration-dependent manner and also appeared to bind collagen type V and laminin, but not other proteins, such as transferrin, heparin, bovine serum albumin, mucin, or collagen IV. We demonstrated that the N terminal fragment of Fnm is required for full fibronectin binding, since truncation of this region caused a 2.4-fold decrease (P < 0.05) in the adhesion of E. faecium TX82 to fibronectin. Deletion of fnm resulted in a significant reduction (P < 0.001) in the ability of the mutant, TX6128, to bind fibronectin relative to that of the wild-type strain; in situ reconstitution of fnm in the deletion mutant strain restored adherence. In addition, the Deltafnm mutant was highly attenuated relative to TX82 (P <= 0.0001) in a mixed-inoculum rat endocarditis model. Taken together, these results demonstrate that Fnm affects the adherence of E. faecium to fibronectin and is important in the pathogenesis of experimental endocarditis. PMID- 26371132 TI - Reply to C.T. Hiley. PMID- 26371131 TI - Interleukin-10 modulates antigen presentation by dendritic cells through regulation of NLRP3 inflammasome assembly during Chlamydia infection. AB - Interleukin-10 (IL-10) has been implicated in susceptibility to genital chlamydial infection and the development of tubal pathologies. IL-10 limitation also resulted in the rapid elicitation of immune responses against Chlamydia, and decreased levels of IL-10 correlated with protective anti-Chlamydia immunity. To investigate the molecular basis for these effects, we compared the reproductive pathologies and fertility rates in Chlamydia-infected wild-type (WT) and IL-10 knockout (IL-10(-/-)) mice; we also analyzed the expression of the Toll-like receptor (TLR)/interleukin-1 receptor (IL-1R) superfamily, IL-1beta production, NLRP3 inflammasome assembly and activation, and the immunostimulatory capacity and apoptotic predilection of Chlamydia-exposed dendritic cells (DCs) from WT and IL-10(-/-) mice. Our results revealed that, in addition to the rapid clearance of infection, genitally infected IL-10(-/-) mice were protected from tubal pathologies and infertility, whereas WT (IL-10(+/+)) mice were not. Chlamydia pulsed IL-10(-/-) DCs expressed larger numbers of TLR4/IL-1R molecules and had enhanced IL-1beta production. In addition, NLRP3 inflammasome assembly was suppressed in IL-10(-/-) DCs through the inhibition of the P2X purinoceptor 7 (P2X7) receptor (P2X7R), an ATP-gated ion channel, and a decrease in intracellular Ca(2+) levels, which inhibited DC apoptosis. Thus, the potent immunostimulatory capacity of IL-10-deficient DCs is due, at least in part, to the suppression of the intracellular inflammasome assembly, which prevents DC apoptosis, allowing efficient antigen presentation. The results indicate that IL 10 deficiency enables efficient antigen presentation by DCs for rapid and enhanced immune activation against Chlamydia, which results in rapid microbial clearance, which prevents tubal pathologies during infection. Our finding has important implications for the induction of protective immunity against Chlamydia and other infectious and noninfectious diseases by vaccines. PMID- 26371133 TI - Cognitive Impairment in Survivors of Irradiated Brain Tumors Is Multifactorial: Implications of Polypharmacy With Antiepileptics? PMID- 26371135 TI - Trabectedin and the L-Sarcomas: A Decade-Long Odyssey. PMID- 26371134 TI - Fulvestrant 500 mg Versus Anastrozole 1 mg for the First-Line Treatment of Advanced Breast Cancer: Overall Survival Analysis From the Phase II FIRST Study. AB - PURPOSE: To compare overall survival (OS) for fulvestrant 500 mg versus anastrozole as first-line endocrine therapy for advanced breast cancer. PATIENTS AND METHODS: The Fulvestrant First-Line Study Comparing Endocrine Treatments (FIRST) was a phase II, randomized, open-label, multicenter trial. Postmenopausal women with estrogen receptor-positive, locally advanced/metastatic breast cancer who had no previous therapy for advanced disease received either fulvestrant 500 mg (days 0, 14, 28, and every 28 days thereafter) or anastrozole 1 mg (daily). The primary end point (clinical benefit rate [72.5% and 67.0%]) and a follow-up analysis (median time to progression [23.4 months and 13.1 months]) have been reported previously for fulvestrant 500 mg and anastrozole, respectively. Subsequently, the protocol was amended to assess OS by unadjusted log-rank test after approximately 65% of patients had died. Treatment effect on OS across several subgroups was examined. Tolerability was evaluated by adverse event monitoring. RESULTS: In total, 205 patients were randomly assigned (fulvestrant 500 mg, n = 102; anastrozole, n = 103). At data cutoff, 61.8% (fulvestrant 500 mg, n = 63) and 71.8% (anastrozole, n = 74) had died. The hazard ratio (95% CI) for OS with fulvestrant 500 mg versus anastrozole was 0.70 (0.50 to 0.98; P = .04; median OS, 54.1 months v 48.4 months). Treatment effects seemed generally consistent across the subgroups analyzed. No new safety issues were observed. CONCLUSION: There are several limitations of this OS analysis, including that it was not planned in the original protocol but instead was added after time-to progression results were analyzed, and that not all patients participated in additional OS follow-up. However, the present results suggest fulvestrant 500 mg extends OS versus anastrozole. This finding now awaits prospective confirmation in the larger phase III FALCON (Fulvestrant and Anastrozole Compared in Hormonal Therapy Naive Advanced Breast Cancer) trial (ClinicalTrials.gov identifier: NCT01602380). PMID- 26371136 TI - Discussing Genetic Testing With Patients With Breast Cancer in Developing Countries: Should We Be Judicious? PMID- 26371137 TI - Reply to S.M. Sorscher and A.B. Hafeez Bhatti. PMID- 26371139 TI - Stem-Cell Transplantation for Amyloidosis: Improving Outcomes but Not for the Faint of Heart. PMID- 26371138 TI - Improved Outcomes After Autologous Hematopoietic Cell Transplantation for Light Chain Amyloidosis: A Center for International Blood and Marrow Transplant Research Study. AB - PURPOSE: Autologous hematopoietic cell transplantation, or autotransplantation, is effective in light-chain amyloidosis (AL), but it is associated with a high risk of early mortality (EM). In a multicenter randomized comparison against oral chemotherapy, autotransplantation was associated with 24% EM. We analyzed trends in outcomes after autologous hematopoietic cell transplantation for AL in North America. PATIENTS AND METHODS: Between 1995 and 2012, 1,536 patients with AL who underwent autotransplantation at 134 centers were identified in the Center for International Blood and Marrow Transplant Research database. EM and overall survival (OS) were analyzed in three time cohorts: 1995 to 2000 (n = 140), 2001 to 2006 (n = 596), and 2007 to 2012 (n = 800). Hematologic and renal responses and factors associated with EM, relapse and/or progression, progression-free survival and OS were analyzed in more recent subgroups from 2001 to 2006 (n = 197) and from 2007 to 2012 (n = 157). RESULTS: Mortality at 30 and 100 days progressively declined over successive time periods from 11% and 20%, respectively, in 1995 to 2000 to 5% and 11%, respectively, in 2001 to 2006, and to 3% and 5%, respectively, in 2007 to 2012. Correspondingly, 5-year OS improved from 55% in 1995 to 2000 to 61% in 2001 to 2006 and to 77% in 2007 to 2012. Hematologic response to transplantation improved in the latest cohort. Renal response rate was 32%. Centers performing more than four AL transplantations per year had superior survival outcomes. In the multivariable analysis, cardiac AL was associated with high EM and inferior progression-free survival and OS. Autotransplantation in 2007 to 2012 and use of higher dosages of melphalan were associated with a lowered relapse risk. A Karnofsky score less than 80 and creatinine levels 2 mg/m(2) or greater were associated with worsened OS. CONCLUSION: Post-transplantation survival in AL has improved, with a dramatic reduction in early post-transplantation mortality and excellent 5-year survival. The risk-benefit ratio for autotransplantation has changed, and randomized comparison with nontransplantation approaches is again warranted. PMID- 26371141 TI - Colorectal Cancer in Young Individuals: Opportunities for Prevention. PMID- 26371140 TI - Tyrosine Kinase Inhibitor-Associated Cardiovascular Toxicity in Chronic Myeloid Leukemia. AB - For most patients with chronic myeloid leukemia, tyrosine kinase inhibitors (TKIs) have turned a fatal disease into a manageable chronic condition. Imatinib, the first BCR-ABL1 TKI granted regulatory approval, has been surpassed in terms of molecular responses by the second-generation TKIs nilotinib, dasatinib, and bosutinib. Recently, ponatinib was approved as the only TKI with activity against the T315I mutation. Although all TKIs are associated with nonhematologic adverse events (AEs), experience with imatinib suggested that toxicities are typically manageable and apparent early during drug development. Recent reports of cardiovascular AEs with nilotinib and particularly ponatinib and of pulmonary arterial hypertension with dasatinib have raised concerns about long-term sequelae of drugs that may be administered for decades. Here, we review what is currently known about the cardiovascular toxicities of BCR-ABL1 TKIs, discuss potential mechanisms underlying cardiovascular AEs, and elucidate discrepancies between the reporting of such AEs between oncology and cardiovascular trials. Whenever possible, we provide practical recommendations, but we concede that cause-directed interventions will require better mechanistic understanding. We suggest that chronic myeloid leukemia heralds a fundamental shift in oncology toward effective but mostly noncurative long-term therapies. Realizing the full potential of these treatments will require a proactive rational approach to minimize long-term cardiovascular and cardiometabolic toxicities. PMID- 26371142 TI - Discussing the Implications of Genetic Testing With Patients. PMID- 26371144 TI - Sentinel Node Biopsy After Neoadjuvant Chemotherapy for Node-Positive Breast Cancer: Does Axillary Ultrasound Improve Performance? PMID- 26371143 TI - Efficacy and Safety of Trabectedin or Dacarbazine for Metastatic Liposarcoma or Leiomyosarcoma After Failure of Conventional Chemotherapy: Results of a Phase III Randomized Multicenter Clinical Trial. AB - PURPOSE: This multicenter study, to our knowledge, is the first phase III trial to compare trabectedin versus dacarbazine in patients with advanced liposarcoma or leiomyosarcoma after prior therapy with an anthracycline and at least one additional systemic regimen. PATIENTS AND METHODS: Patients were randomly assigned in a 2:1 ratio to receive trabectedin or dacarbazine intravenously every 3 weeks. The primary end point was overall survival (OS), secondary end points were disease control-progression-free survival (PFS), time to progression, objective response rate, and duration of response-as well as safety and patient reported symptom scoring. RESULTS: A total of 518 patients were enrolled and randomly assigned to either trabectedin (n = 345) or dacarbazine (n = 173). In the final analysis of PFS, trabectedin administration resulted in a 45% reduction in the risk of disease progression or death compared with dacarbazine (median PFS for trabectedin v dacarbazine, 4.2 v 1.5 months; hazard ratio, 0.55; P < .001); benefits were observed across all preplanned subgroup analyses. The interim analysis of OS (64% censored) demonstrated a 13% reduction in risk of death in the trabectedin arm compared with dacarbazine (median OS for trabectedin v dacarbazine, 12.4 v 12.9 months; hazard ratio, 0.87; P = .37). The safety profiles were consistent with the well-characterized toxicities of both agents, and the most common grade 3 to 4 adverse effects were myelosuppression and transient elevation of transaminases in the trabectedin arm. CONCLUSION: Trabectedin demonstrates superior disease control versus conventional dacarbazine in patients who have advanced liposarcoma and leiomyosarcoma after they experience failure of prior chemotherapy. Because disease control in advanced sarcomas is a clinically relevant end point, this study supports the activity of trabectedin for patients with these malignancies. PMID- 26371146 TI - Improving Prospects for Targeting RAS. AB - RAS mutations are among the most common oncogenic drivers in human cancers, affecting nearly a third of all solid tumors and around a fifth of common myeloid malignancies, but they have evaded therapeutic interventions, despite being the focus of intense research over the last three decades. Recent discoveries lend new understanding about the structure, function, and signaling of RAS and have opened new avenues for development of much needed new therapies. We discuss the various approaches under investigation to target mutant RAS proteins. The recent development of direct RAS inhibitors specific to KRAS G12C mutations represents a landmark discovery that promises to change the perception about RAS's druggability. Multiple clinical trials targeting synthetically lethal partners and/or downstream signaling partners of RAS are underway. Novel inhibitors targeting various arms of RAS processing and signaling have yielded encouraging results in the laboratory, but refinement of the drug-like properties of these molecules is required before they will be ready for the clinic. PMID- 26371145 TI - Lobular Carcinoma in Situ: A 29-Year Longitudinal Experience Evaluating Clinicopathologic Features and Breast Cancer Risk. AB - PURPOSE: The increased breast cancer risk conferred by a diagnosis of lobular carcinoma in situ (LCIS) is poorly understood. Here, we review our 29-year longitudinal experience with LCIS to evaluate factors associated with breast cancer risk. PATIENTS AND METHODS: Patients participating in surveillance after an LCIS diagnosis are observed in a prospectively maintained database. Comparisons were made among women choosing surveillance, with or without chemoprevention, and those undergoing bilateral prophylactic mastectomies between 1980 and 2009. RESULTS: One thousand sixty patients with LCIS without concurrent breast cancer were identified. Median age at LCIS diagnosis was 50 years (range, 27 to 83 years). Fifty-six patients (5%) underwent bilateral prophylactic mastectomy; 1,004 chose surveillance with (n = 173) or without (n = 831) chemoprevention. At a median follow-up of 81 months (range, 6 to 368 months), 150 patients developed 168 breast cancers (63% ipsilateral, 25% contralateral, 12% bilateral), with no dominant histology (ductal carcinoma in situ, 35%; infiltrating ductal carcinoma, 29%; infiltrating lobular carcinoma, 27%; other, 9%). Breast cancer incidence was significantly reduced in women taking chemoprevention (10-year cumulative risk: 7% with chemoprevention; 21% with no chemoprevention; P < .001). In multivariable analysis, chemoprevention was the only clinical factor associated with breast cancer risk (hazard ratio, 0.27; 95% CI, 0.15 to 0.50). In a subgroup nested case-control analysis, volume of disease, which was defined as the ratio of slides with LCIS to total number of slides reviewed, was also associated with breast cancer development (P = .008). CONCLUSION: We observed a 2% annual incidence of breast cancer among women with LCIS. Common clinical factors used for risk prediction, including age and family history, were not associated with breast cancer risk. The lower breast cancer incidence in women opting for chemoprevention highlights the potential for risk reduction in this population. PMID- 26371147 TI - Comparison of the Genomic Landscape Between Primary Breast Cancer in African American Versus White Women and the Association of Racial Differences With Tumor Recurrence. AB - PURPOSE: African American women are more likely to die as a result of breast cancer than white women. The influence of somatic genomic profiles on this racial disparity is unclear. We aimed to compare the racial distribution of tumor genomic characteristics and breast cancer recurrence. METHODS: We assessed white and African American women with stage I to III breast cancer diagnosed from 1988 to 2013 and primary tumors submitted to The Cancer Genome Atlas from 2010 to 2014. We used Cox proportional hazards models to evaluate the association of race and genetic traits with tumor recurrence. RESULTS: We investigated exome sequencing and gene expression data in 663 and 711 white and 105 and 159 African American women, respectively. African Americans had more TP53 mutations (42.9% v 27.6%; P = .003) and fewer PIK3CA mutations (20.0% v 33.9%; P = .008). Intratumor genetic heterogeneity was greater in African American than white tumors overall by 5.1 units (95% CI, 2.4 to 7.7) and within triple-negative tumors by 4.1 units (95% CI, 1.4 to 6.8). African Americans had more basal tumors by the 50-gene set predictor using the predication analysis of microarray method (PAM50; 39.0% v 18.6%; P < .001) and fewer PAM50 luminal A tumors (17.0% v 34.7%; P < .001). Among triple-negative subtypes, African Americans had more basal-like 1 and mesenchymal stem-like tumors. African Americans had a higher risk of tumor recurrence than whites (hazard ratio, 2.22; 95% CI, 1.05 to 4.67). Racial differences in TP53 mutation, PAM50 basal subtype, and triple-negative tumor prevalence but not intratumor genetic heterogeneity influenced the magnitude and significance of the racial disparity in tumor recurrence. CONCLUSION: African Americans had greater intratumor genetic heterogeneity and more basal gene expression tumors, even within triple-negative breast cancer. This pattern suggests more aggressive tumor biology in African Americans than whites, which could contribute to racial disparity in breast cancer outcome. PMID- 26371149 TI - Recombinant production of omega-3 fatty acids by probiotic Escherichia coli Nissle 1917. AB - Omega-3 fatty acids, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have beneficial effects on human health. The probiotic bacterium Escherichia coli Nissle is unable to produce either EPA or DHA. Escherichia coli Nissle was transformed with the pfBS-PS plasmid carrying the EPA/DHA gene cluster, previously isolated from a marine bacterium. The transgenic E. coli Nissle produced EPA when grown at 10oC (16.52 +/- 1.4 mg g(-1) cell dry weight), 15oC (31.36 +/- 0.25 mg g(-1) cell dry weight), 20oC (13.71 +/- 2.8 mg g(-1) cell dry weight), 25oC (11.33 +/- 0.44 mg g(-1) cell dry weight) or 30oC (0.668 +/- 0.073 mg g(-1) cell dry weight). Although DHA was also produced at all these temperatures, it comprised less than 0.2% of total extracted fatty acids. Transcriptomic analysis using Reverse Transcription qPCR showed upregulation of the entire gene cluster in E. coli Nissle. Among EPA/DHA genes, pfaB, pfaC and pfaD were overexpressed (expression ratio of 181.9, 39.86 and 131.61, respectively) as compared to pfaA (expression ratio of 3.40) and pfaE (expression ratio of 4.05). The EPA/DHA-producing probiotic E. coli Nissle may be used as a safe, alternative and economic source for the industrial and pharmaceutical production of EPA and DHA. PMID- 26371148 TI - Surgical Excision Without Radiation for Ductal Carcinoma in Situ of the Breast: 12-Year Results From the ECOG-ACRIN E5194 Study. AB - PURPOSE: To determine the 12-year risk of developing an ipsilateral breast event (IBE) for women with ductal carcinoma in situ (DCIS) of the breast treated with surgical excision (lumpectomy) without radiation. PATIENTS AND METHODS: A prospective clinical trial was performed for women with DCIS who were selected for low-risk clinical and pathologic characteristics. Patients were enrolled onto one of two study cohorts (not randomly assigned): cohort 1: low- or intermediate grade DCIS, tumor size 2.5 cm or smaller (n = 561); or cohort 2: high-grade DCIS, tumor size 1 cm or smaller (n = 104). Protocol specifications included excision of the DCIS tumor with a minimum negative margin width of at least 3 mm. Tamoxifen (not randomly assigned) was given to 30% of the patients. An IBE was defined as local recurrence of DCIS or invasive carcinoma in the treated breast. Median follow-up time was 12.3 years. RESULTS: There were 99 IBEs, of which 51 (52%) were invasive. The IBE and invasive IBE rates increased over time in both cohorts. The 12-year rates of developing an IBE were 14.4% for cohort 1 and 24.6% for cohort 2 (P = .003). The 12-year rates of developing an invasive IBE were 7.5% and 13.4%, respectively (P = .08). On multivariable analysis, study cohort and tumor size were both significantly associated with developing an IBE (P = .009 and P = .03, respectively). CONCLUSION: For patients with DCIS selected for favorable clinical and pathologic characteristics and treated with excision without radiation, the risks of developing an IBE and an invasive IBE increased through 12 years of follow-up, without plateau. These data help inform the treatment decision-making process for patients and their physicians. PMID- 26371150 TI - Surgical excision of a giant calcified amorphous tumour of the right ventricle and right pulmonary artery. AB - A cardiac calcified amorphous tumour (CCAT) is a rare non-neoplastic intracavitary mass with unknown causes. We describe a 32-year old male presenting with progressive dyspnoea, cough and oedemas. The transthoracic echocardiography and contrast-enhanced angio-computed tomography demonstrated a 4 * 10 cm calcified mass into the right ventricle and total occlusion of the right pulmonary artery. The patient underwent successful total removal of the mass through a transverse right ventriculotomy, and right pulmonary embolectomy. Histopathological examination of mass confirmed the diagnosis of a CCAT. The postoperative course was uneventful. To our knowledge, this is the first reported case with a confirmed diagnosis of CCAT at two different locations and the third undergoing a combined approach aiming at total mass excision. PMID- 26371151 TI - Tricuspid valve repair in patients with left-ventricular assist device implants and tricuspid valve regurgitation: propensity score-adjusted analysis of clinical outcome. AB - OBJECTIVES: In end-stage heart failure patients with left-ventricular assist device implantation and tricuspid valve (TV) regurgitation grade >2, the surgical strategy for TV regurgitation is unclear at present. We aimed to compare clinical outcomes in patients receiving left-ventricular assist device (LVAD) implants with or without TV repair (TVR). METHODS: We included 58 patients with TV regurgitation grade >2 in our data analysis. Thirty-two patients received TVR during LVAD implantation (TVR+ group), whereas 26 patients did not receive TVR (TVR- group). We assessed demographic and various preoperative clinical and echocardiographic parameters in both groups. The primary end-point was survival up to 1 year. Secondary end-points were the incidence of prolonged mechanical ventilatory support, rethoracotomy, early and late right heart failure and liver or kidney failure. RESULTS: Preoperatively, the two groups differed according to heart failure diagnosis, need for inotropic support and haemodynamic/echocardiographic parameters such as transpulmonary gradient, cardiac index and the ratio of the right-ventricular end-diastolic diameter to the left-ventricular end-diastolic diameter. The survival rate up to 1 year was 53.1% in the TVR+ group and 73.1% in the TVR- group (P = 0.176). The propensity score (PS)-adjusted 1-year mortality risk with the TVR- group as a reference was 3.05 for the TVR+ group (95% confidence interval: 0.84-11.11; P = 0.091). Secondary end-points did not differ significantly between study groups. CONCLUSIONS: Data indicate that end-stage heart failure patients with TV regurgitation grade >2 undergoing LVAD implants do not benefit from concomitant TVR. Results have to be confirmed by prospective studies. PMID- 26371152 TI - Grazoprevir, Elbasvir, and Ribavirin for Chronic Hepatitis C Virus Genotype 1 Infection After Failure of Pegylated Interferon and Ribavirin With an Earlier Generation Protease Inhibitor: Final 24-Week Results From C-SALVAGE. AB - BACKGROUND: The phase 2 C-SALVAGE study (Hepatitis C-Salvage Study for Patients who Failed DAA/PR Therapy) demonstrated a 96.2% sustained virologic response at 12 weeks (SVR12) rate using the NS3/4A protease inhibitor grazoprevir and the NS5A inhibitor elbasvir together with ribavirin in treatment-experienced patients with chronic hepatitis C virus (HCV) genotype 1 infection. METHODS: C-SALVAGE was a prospective open-label trial of grazoprevir 100 mg once daily and elbasvir 50 mg once daily coadministered with weight-based ribavirin twice daily for 12 weeks in genotype 1-infected cirrhotic and noncirrhotic patients who had failed treatment with >= 4 weeks of pegylated interferon and ribavirin plus either boceprevir, telaprevir, or simeprevir. Although the primary efficacy outcome was SVR12, patients were also evaluated 24 weeks after cessation of study therapy. Population sequencing was performed at baseline and periodically in virologic failures throughout the 24-week posttherapy follow-up period. RESULTS: SVR24 rates were 76 of 79 (96.2%) overall, with all 3 relapses occurring by posttherapy week 8. Every NS3 and NS5A variant detected at baseline reappeared at the time of relapse and persisted throughout the available follow-up period. NS3_A156T emerged in virus from each patient at relapse, but rapidly disappeared over the ensuing 2 weeks in 2 patients. NS5A_Y93H emerged in virus from 2 patients at relapse and persisted for the entire follow-up period. CONCLUSIONS: Grazoprevir and elbasvir with ribavirin for 12 weeks maintained HCV suppression for at least 24 weeks posttherapy without late relapses. Baseline resistance-associated variants (RAVs) stably reappeared at relapse in all 3 patients with virologic failure. NS5A_RAVs emerging at relapse persisted for the full 24-week follow-up period. If confirmed, this finding could complicate retreatment of the small number of patients failing regimens containing an NS5A inhibitor. CLINICAL TRIALS REGISTRATION: NCT02105454. PMID- 26371153 TI - Reply to Musher. PMID- 26371154 TI - Genetic Control of Antibody Responses to Pneumococcal Capsular Polysaccharides. PMID- 26371155 TI - Impact of Global Health Research Training on Scholarly Productivity: The Fogarty International Clinical Research Scholars and Fellows Program. AB - In the Fogarty International Clinical Research Scholars and Fellows (FICRS-F) Program, 536 U.S. and international doctoral and postdoctoral health profession students and trainees completed 1-year research training at research centers in low- and middle-income countries. To evaluate the Program's impact, we analyzed data gathered prospectively during the Program, from PubMed, and from a representative survey of alumni. Of 100 randomly selected respondents, 94 returned the survey. Reflecting the sources of funding, human immunodeficiency virus/acquired immunodeficiency syndrome was the focus of 47% of the projects, but research in noncommunicable diseases (NCDs) and dual infection/NCD-related topics increased over time. Among the first 1,617 alumni publications, output was associated positively with being an international versus U.S. trainee, a postdoctoral Fellow versus predoctoral Scholar, and accumulation of more years post-training (all P < 0.001). Fellows were first author on a higher proportion of their articles than were Scholars (P < 0.001), and U.S. trainees were more often first author than international trainees (P = 0.04). Survey respondents had submitted 117 grant applications, and 79 (67.5%) had been funded. The FICRS-F Program yielded substantial research productivity in the early post-training years. Research outputs and impact will increase over time as alumni careers mature and they gain research independence and assume leadership positions. PMID- 26371156 TI - DNA Barcoding of Gypsy Moths From China (Lepidoptera: Erebidae) Reveals New Haplotypes and Divergence Patterns Within Gypsy Moth Subspecies. AB - The gypsy moth from Asia (two subspecies) is considered a greater threat to North America than European gypsy moth, because of a broader host range and females being capable of flight. Variation within and among gypsy moths from China (nine locations), one of the native countries of Asian gypsy moth, were compared using DNA barcode sequences (658 bp of mtDNA cytochrome c oxidase subunit 1 [COI] sequence), together with two restriction site mtDNA markers (NlaIII and BamHI in COI), which is the standard system used to distinguish European gypsy moths from Asian gypsy moths. Relatedness of these populations to gypsy moths from seven other world areas was also examined. The restriction site markers showed that two Chinese populations had both Asian and European haplotypes. DNA barcode sequence divergence between the Asian populations and the European populations was three times greater than the variation within each group. Using Bayesian and parsimonious network analyses, nine previously unknown barcode haplotypes were documented from China and a single haplotype was found to be shared by 55% of the Chinese and some Far Eastern Russian and Japanese individuals. Some gypsy moths from two Chinese populations showed genetic affinity with mtDNA haplotypes from Siberia, Russia, suggesting there could be a cryptic new subspecies in Lymantria dispar (L.) or human-aided movement of moths between these two locations at an earlier point in time. The previously unknown haplotype patterns may complicate efforts to identify Asian gypsy moth introductions and require changes in monitoring and exclusion programs. PMID- 26371157 TI - Childhood intussusception: 17-year experience at a tertiary referral centre in Hong Kong. AB - OBJECTIVES: To review all paediatric patients with intussusception over the last 17 years. DESIGN: Retrospective case series. SETTING: A tertiary centre in Hong Kong. PATIENTS: Children who presented with intussusception from January 1997 to December 2014 were reviewed. MAIN OUTCOME MEASURES: The duration of symptoms, successful treatment modalities, complication rate, and length of hospital stay were studied. RESULTS: A total of 173 children (108 male, 65 female) presented to our hospital with intussusception during the study period. Their median age at presentation was 12.5 months (range, 2 months to 16 years) and the mean duration of symptoms was 2.3 (standard deviation, 1.8) days. Vomiting was the most common symptom (76.3%) followed by abdominal pain (46.2%), per rectal bleeding or red currant jelly stool (40.5%), and a palpable abdominal mass (39.3%). Overall, 160 patients proceeded to pneumatic or hydrostatic reduction, among whom 127 (79.4%) were successful. Three (1.9%) patients had bowel perforation during the procedure. Early recurrence of intussusception occurred in four (3.1%) patients with non-operative reduction. No recurrence was reported in the operative group. The presence of a palpable abdominal mass was a risk factor for operative treatment (relative risk=2.0; 95% confidence interval, 1.8-2.2). Analysis of our results suggested that duration of symptoms did not affect the success rate of non-operative reduction. CONCLUSIONS: Non-operative reduction has a high success rate and low complication rate, but the presence of a palpable abdominal mass is a risk factor for failure. Operative intervention should not be delayed in those patients who encounter difficult or doubtful non-operative reduction. PMID- 26371158 TI - Intensive care unit family satisfaction survey. AB - OBJECTIVES: To examine the level of family satisfaction in a local intensive care unit and its performance in comparison with international standards, and to determine the factors independently associated with higher family satisfaction. DESIGN: Questionnaire survey. SETTING: A medical-surgical adult intensive care unit in a regional hospital in Hong Kong. PARTICIPANTS: Adult family members of patients admitted to the intensive care unit for 48 hours or more between 15 June 2012 and 31 January 2014, and who had visited the patient at least once during their stay. RESULTS: Of the 961 eligible families, 736 questionnaires were returned (response rate, 76.6%). The mean (+/- standard deviation) total satisfaction score, and subscores on satisfaction with overall intensive care unit care and with decision-making were 78.1 +/- 14.3, 78.0 +/- 16.8, and 78.6 +/ 13.6, respectively. When compared with a Canadian multicentre database with respective mean scores of 82.9 +/- 14.8, 83.5 +/- 15.4, and 82.6 +/- 16.0 (P<0.001), there was still room for improvement. Independent factors associated with complete satisfaction with overall care were concern for patients and families, agitation management, frequency of communication by nurses, physician skill and competence, and the intensive care unit environment. A performance importance plot identified the intensive care unit environment and agitation management as factors that required more urgent attention. CONCLUSIONS: This is the first intensive care unit family satisfaction survey published in Hong Kong. Although comparable with published data from other parts of the world, the results indicate room for improvement when compared with a Canadian multicentre database. Future directions should focus on improving the intensive care unit environment, agitation management, and communication with families. PMID- 26371159 TI - Quantitative Proteome Analysis Reveals Increased Content of Basement Membrane Proteins in Arteries From Patients With Type 2 Diabetes Mellitus and Lower Levels Among Metformin Users. AB - BACKGROUND: The increased risk of cardiovascular diseases in type 2 diabetes mellitus has been extensively documented, but the origins of the association remain largely unknown. We sought to determine changes in protein expressions in arterial tissue from patients with type 2 diabetes mellitus and moreover hypothesized that metformin intake influences the protein composition. METHODS AND RESULTS: We analyzed nonatherosclerotic repair arteries gathered at coronary bypass operations from 30 patients with type 2 diabetes mellitus and from 30 age- and sex-matched nondiabetic individuals. Quantitative proteome analysis was performed by isobaric tag for relative and absolute quantitation-labeling and liquid chromatography-mass spectrometry, tandem mass spectrometry analysis on individual arterial samples. The amounts of the basement membrane components, alpha1-type IV collagen and alpha2-type IV collagen, gamma1-laminin and beta2 laminin, were significantly increased in patients with diabetes mellitus. Moreover, the expressions of basement membrane components and other vascular proteins were significantly lower among metformin users when compared with nonusers. Patients treated with or without metformin had similar levels of hemoglobin A1c, cholesterol, and blood pressure. In addition, quantitative histomorphometry showed increased area fractions of collagen-stainable material in tunica intima and media among patients with diabetes mellitus. CONCLUSIONS: The distinct accumulation of arterial basement membrane proteins in type 2 diabetes mellitus discloses a similarity between the diabetic macroangiopathy and microangiopathy and suggests a molecular explanation behind the alterations in vascular remodeling, biomechanical properties, and aneurysm formation described in diabetes mellitus. The lower amounts of basement membrane components in metformin-treated individuals are compatible with the hypothesis of direct beneficial drug effects on the matrix composition in the vasculature. PMID- 26371160 TI - NPY1-36 and PYY1-36 activate cardiac fibroblasts: an effect enhanced by genetic hypertension and inhibition of dipeptidyl peptidase 4. AB - Cardiac sympathetic nerves release neuropeptide Y (NPY)1-36, and peptide YY (PYY)1-36 is a circulating peptide; therefore, these PP-fold peptides could affect cardiac fibroblasts (CFs). We examined the effects of NPY1-36 and PYY1-36 on the proliferation of and collagen production ([(3)H]proline incorporation) by CFs isolated from Wistar-Kyoto (WKY) normotensive rats and spontaneously hypertensive rats (SHRs). Experiments were performed with and without sitagliptin, an inhibitor of dipeptidyl peptidase 4 [DPP4; an ectoenzyme that metabolizes NPY1-36 and PYY1-36 (Y1 receptor agonists) to NPY3-36 and PYY3-36 (inactive at Y1 receptors), respectively]. NPY1-36 and PYY1-36, but not NPY3-36 or PYY3-36, stimulated proliferation of CFs, and these effects were more potent than ANG II, enhanced by sitagliptin, blocked by BIBP3226 (Y1 receptor antagonist), and greater in SHR CFs. SHR CF membranes expressed more receptor for activated C kinase (RACK)1 [which scaffolds the Gi/phospholipase C (PLC)/PKC pathway] compared with WKY CF membranes. RACK1 knockdown (short hairpin RNA) and inhibition of Gi (pertussis toxin), PLC (U73122), and PKC (GF109203X) blocked the proliferative effects of NPY1-36. NPY1-36 and PYY1-36 stimulated collagen production more potently than did ANG II, and this was enhanced by sitagliptin and greater in SHR CFs. In conclusion, 1) NPY1-36 and PYY1-36, via the Y1 receptor/Gi/PLC/PKC pathway, activate CFs, and this pathway is enhanced in SHR CFs due to increased localization of RACK1 in membranes; and 2) DPP4 inhibition enhances the effects of NPY1-36 and PYY1-36 on CFs, likely by inhibiting the metabolism of NPY1-36 and PYY1-36. The implications are that endogenous NPY1-36 and PYY1-36 could adversely affect cardiac structure/function by activating CFs, and this may be exacerbated in genetic hypertension and by DPP4 inhibitors. PMID- 26371161 TI - MicroRNA-141 regulates the expression level of ICAM-1 on endothelium to decrease myocardial ischemia-reperfusion injury. AB - A growing number of studies have suggested microRNAs (miRNAs) are involved in the modulation of myocardial ischemia-reperfusion (MI/R) injury; however, the role of endogenous miRNAs targeting endothelial cells (ECs) and its interaction with ICAM 1 in the setting of MI/R remain poorly understood. Our microarray results showed that miR-146a, miR-146b-5p, miR-155*, miR-155, miR-497, and miR-451 were significantly upregulated, whereas, miR-141 and miR-564 were significantly downregulated in the ECs challenged with TNF-alpha for 6 h. Real-time PCR analyses additionally validated that the expression levels of miR-146a, miR-155*, and miR-141 were consistent with the microarray results. Then, ICAM-1 was identified as a novel target of miR-141 by Target Scan software and the reporter gene system. Further functional experiments showed that elevated levels of miR 141 inhibited ICAM-1 expression and diminished leukocytes adhesion to ECs in vitro. In an in vivo murine model of MI/R injury, pretreatment with miR-141 mimics through the tail vein downregulated the expression level of ICAM-1 in heart and attenuated MI/R injury as evidenced by decreased infarct size and decline of serum cardial troponin I (cTnI) and lactate dehydrogenase (LDH) concentration. The cardioprotective effects of miR-141 mimics may be attributed to the decreased infiltration of CD11b(+) cells and F4/80(+) macrophages into ischemic myocardium tissue. In conclusion, our results demonstrate that miR-141, as a novel repressor of ICAM-1, is involved in the attenuation of MI/R injury via antithetical regulation of ICAM-1 and inflammatory cells infiltration. Thus miR 141 may constitute a new therapeutic target in the setting of ischemic heart disease. PMID- 26371163 TI - Aerobic exercise training-induced changes in serum adropin level are associated with reduced arterial stiffness in middle-aged and older adults. AB - Aging-induced arterial stiffening is reduced by aerobic exercise training, and elevated production of nitric oxide (NO) participates in this effect. Adropin is a regulator of endothelial NO synthase and NO release, and circulating adropin level decreases with age. However, the effect of habitual aerobic exercise on circulating adropin levels in healthy middle-aged and older adults remains unclear. We sought to determine whether serum adropin level is associated with exercise training-induced changes in arterial stiffness. First, in a cross sectional study, we investigated the association between serum adropin level and both arterial stiffness and cardiorespiratory fitness in 80 healthy middle-aged and older subjects (65.6 +/- 0.9 yr). Second, in an intervention study, we examined the effects of 8-wk aerobic exercise training on serum adropin level and arterial stiffness in 40 healthy middle-aged and older subjects (67.3 +/- 1.0 yr) divided into two groups: aerobic exercise training and sedentary controls. In the cross-sectional study, serum adropin level was negatively correlated with carotid beta-stiffness (r = -0.437, P < 0.001) and positively correlated with plasma NOx level (r = 0.493, P < 0.001) and cardiorespiratory fitness (r = 0.457, P < 0.001). Serum adropin levels were elevated after the 8-wk aerobic exercise training intervention, and training-induced changes in serum adropin level were correlated with training-induced changes in carotid beta-stiffness (r = -0.399, P < 0.05) and plasma NOx level (r = 0.623, P < 0.001). Thus the increase in adropin may participate in the exercise-induced reduction of arterial stiffness. PMID- 26371162 TI - The role of beta-arrestin2-dependent signaling in thoracic aortic aneurysm formation in a murine model of Marfan syndrome. AB - Ang II type 1a receptor (AT1aR)-mediated activation of MAPKs contributes to thoracic aortic aneurysm (TAA) development in Marfan syndrome (MFS). beta Arrestin2 (betaarr2) is known to mediate AT1aR-dependent MAPK activation, as well as proproliferative and profibrotic signaling in aortic vascular smooth muscle cells. Therefore, we investigated whether betaarr2-dependent signaling contributes to TAA formation in MFS. We used a murine model of MFS [fibrillin (Fbn)(C1039G/+)] to generate an MFS murine model in combination with genetic betaarr2 deletion (Fbn(C1039G/+)/betaarr2(-/-)). Fbn(C1039G/+)/betaarr2(-/-) mice displayed delayed aortic root dilation compared with Fbn(C1039G/+) mice. The mRNA and protein expression of several mediators of TAA formation, including matrix metalloproteinase (MMP)-2 and -9, was reduced in the aorta of Fbn(C1039G/+)/betaarr2(-/-) mice relative to Fbn(C1039G/+) mice. Activation of ERK1/2 was also decreased in the aortas of Fbn(C1039G/+)/betaarr2(-/-) mice compared with Fbn(C1039G/+) animals. Small interfering RNA targeting betaarr2 inhibited angiotensin-stimulated expression of proaneurysmal signaling mediators in primary aortic root smooth muscle cells. Angiotensin-stimulated expression of the proaneurysmal signaling mediators MMP-2 and -9 was inhibited by blockade of ERK1/2 or the EGF receptor, whereas blockade of the transforming growth factor beta receptor had no effect. These results suggest that betaarr2 contributes to TAA formation in MFS by regulating ERK1/2-dependent expression of proaneurysmal genes and proteins downstream of the AT1aR. Importantly, this demonstration of the unique signaling mechanism by which betaarr2 contributes to aneurysm formation identifies multiple novel, potential therapeutic targets in MFS. PMID- 26371164 TI - Loss of Rad-GTPase produces a novel adaptive cardiac phenotype resistant to systolic decline with aging. AB - Rad-GTPase is a regulator of L-type calcium current (LTCC), with increased calcium current observed in Rad knockout models. While mouse models that result in elevated LTCC have been associated with heart failure, our laboratory and others observe a hypercontractile phenotype with enhanced calcium homeostasis in Rad(-/-). It is currently unclear whether this observation represents an early time point in a decompensatory progression towards heart failure or whether Rad loss drives a novel phenotype with stable enhanced function. We test the hypothesis that Rad(-/-) drives a stable nonfailing hypercontractile phenotype in adult hearts, and we examine compensatory regulation of sarcoplasmic reticulum (SR) loading and protein changes. Heart function was measured in vivo with echocardiography. In vivo heart function was significantly improved in adult Rad( /-) hearts compared with wild type. Heart wall dimensions were significantly increased, while heart size was decreased, and cardiac output was not changed. Cardiac function was maintained through 18 mo of age with no decompensation. SR releasable Ca(2+) was increased in isolated Rad(-/-) ventricular myocytes. Higher Ca(2+) load was accompanied by sarco/endoplasmic reticulum Ca(2+) ATPase 2a (SERCA2a) protein elevation as determined by immunoblotting and a rightward shift in the thapsigargan inhibitor-response curve. Rad(-/-) promotes morphological changes accompanied by a stable increase in contractility with aging and preserved cardiac output. The Rad(-/-) phenotype is marked by enhanced systolic and diastolic function with increased SR uptake, which is consistent with a model that does not progress into heart failure. PMID- 26371166 TI - Coagulation changes during lower body negative pressure and blood loss in humans. AB - We tested the hypothesis that markers of coagulation activation are greater during lower body negative pressure (LBNP) than those obtained during blood loss (BL). We assessed coagulation using both standard clinical tests and thrombelastography (TEG) in 12 men who performed a LBNP and BL protocol in a randomized order. LBNP consisted of 5-min stages at 0, -15, -30, and -45 mmHg of suction. BL included 5 min at baseline and following three stages of 333 ml of blood removal (up to 1,000 ml total). Arterial blood draws were performed at baseline and after the last stage of each protocol. We found that LBNP to -45 mmHg is a greater central hypovolemic stimulus versus BL; therefore, the coagulation markers were plotted against central venous pressure (CVP) to obtain stimulus-response relationships using the linear regression line slopes for both protocols. Paired t-tests were used to determine whether the slopes of these regression lines fell on similar trajectories for each protocol. Mean regression line slopes for coagulation markers versus CVP fell on similar trajectories during both protocols, except for TEG alpha degrees angle (-0.42 +/- 0.96 during LBNP vs. -2.41 +/- 1.13 degrees /mmHg during BL; P < 0.05). During both LBNP and BL, coagulation was accelerated as evidenced by shortened R-times (LBNP, 9.9 +/- 2.4 to 6.2 +/- 1.1; BL, 8.7 +/- 1.3 to 6.4 +/- 0.4 min; both P < 0.05). Our results indicate that LBNP models the general changes in coagulation markers observed during BL. PMID- 26371165 TI - Effects of nitrite infusion on skeletal muscle vascular control during exercise in rats with chronic heart failure. AB - Chronic heart failure (CHF) reduces nitric oxide (NO) bioavailability and impairs skeletal muscle vascular control during exercise. Reduction of NO2 (-) to NO may impact exercise-induced hyperemia, particularly in muscles with pathologically reduced O2 delivery. We tested the hypothesis that NO2 (-) infusion would increase exercising skeletal muscle blood flow (BF) and vascular conductance (VC) in CHF rats with a preferential effect in muscles composed primarily of type IIb + IId/x fibers. CHF (coronary artery ligation) was induced in adult male Sprague Dawley rats. After a >21-day recovery, mean arterial pressure (MAP; carotid artery catheter) and skeletal muscle BF (radiolabeled microspheres) were measured during treadmill exercise (20 m/min, 5% incline) with and without NO2 (-) infusion. The myocardial infarct size (35 +/- 3%) indicated moderate CHF. NO2 (-) infusion increased total hindlimb skeletal muscle VC (CHF: 0.85 +/- 0.09 ml.min( 1).100 g(-1).mmHg(-1) and CHF + NO2 (-): 0.93 +/- 0.09 ml.min(-1).100 g(-1).mmHg( 1), P < 0.05) without changing MAP (CHF: 123 +/- 4 mmHg and CHF + NO2 (-): 120 +/ 4 mmHg, P = 0.17). Total hindlimb skeletal muscle BF was not significantly different (CHF: 102 +/- 7 and CHF + NO2 (-): 109 +/- 7 ml.min(-1).100 g(-1) ml.min(-1).100 g(-1), P > 0.05). BF increased in 6 (~21%) and VC in 8 (~29%) of the 28 individual muscles and muscle parts. Muscles and muscle portions exhibiting greater BF and VC after NO2 (-) infusion comprised >=63% type IIb + IId/x muscle fibers. These data demonstrate that NO2 (-) infusion can augment skeletal muscle vascular control during exercise in CHF rats. Given the targeted effects shown herein, a NO2 (-)-based therapy may provide an attractive "needs based" approach for treatment of the vascular dysfunction in CHF. PMID- 26371167 TI - Irisin improves endothelial function in obese mice through the AMPK-eNOS pathway. AB - Irisin is a novel hormone secreted by myocytes. Lower levels of irisin are independently associated with endothelial dysfunction in obese subjects. The objective of this study was to explore whether irisin exerts a direct vascular protective effect on endothelial function in high-fat-diet-induced obese mice. Male C57BL/6 mice were given chow or a high-fat diet with or without treatment with irisin. Aortic endothelial function was determined by measuring endothelium dependent vasodilatation (EDV). Nitric oxide (NO) in the aorta was determined. The effect of irisin on the levels of AMP-activated protein kinase (AMPK), Akt, and endothelial NO synthase (eNOS) phosphorylation in endothelial cells was determined. Human umbilical vein endothelial cells were used to study the role of irisin in the AMPK-eNOS pathway. Acetylcholine-stimulated EDV was significantly lower in obese mice compared with control mice. Treatment of obese mice with irisin significantly enhanced EDV and improved endothelial function. This beneficial effect of irisin was partly attenuated in the presence of inhibitors of AMPK, Akt, and eNOS. Treatment of obese mice with irisin enhanced NO production and phosphorylation of AMPK, Akt, and eNOS in endothelial cells. These factors were also enhanced by irisin in human umbilical vein endothelial cells in vitro. Suppression of AMPK expression by small interfering RNA blocked irisin induced eNOS and Akt phosphorylation and NO production. We have provided the first evidence that irisin improves endothelial function in aortas of high-fat diet-induced obese mice. The mechanism for this protective effect is related to the activation of the AMPK-eNOS signaling pathway. PMID- 26371168 TI - Healthy older humans exhibit augmented carotid-cardiac baroreflex sensitivity with aspirin during muscle mechanoreflex and metaboreflex activation. AB - Low-dose aspirin inhibits thromboxane production and augments the sensitivity of carotid baroreflex (CBR) control of heart rate (HR) during concurrent muscle mechanoreflex and metaboreflex activation in healthy young humans. However, it is unknown how aging affects this response. Therefore, the effect of low-dose aspirin on carotid-cardiac baroreflex sensitivity during muscle mechanoreflex with and without metaboreflex activation in healthy older humans was examined. Twelve older subjects (6 men and 6 women, mean age: 62 +/- 1 yr) performed two trials during two visits preceded by 7 days of low-dose aspirin (81 mg) or placebo. One trial involved 3 min of passive calf stretch (mechanoreflex) during 7.5 min of limb circulatory occlusion (CO). In another trial, CO was preceded by 1.5 min of 70% maximal voluntary contraction isometric calf exercise (mechanoreflex and metaboreflex). HR (ECG) and mean arterial blood pressure (MAP; Finometer) were recorded. CBR function was assessed using rapid neck pressure application (+40 to -80 mmHg). Aspirin significantly decreased baseline thromboxane B2 production by 83 +/- 4% (P < 0.05) but did not affect 6-keto PGF1alpha. After aspirin, CBR-HR maximal gain and operating point gain were significantly higher during stretch with metabolite accumulation compared with placebo (maximal gain: -0.23 +/- 0.03 vs. -0.14 +/- 0.02 and operating point gain: -0.11 +/- 0.03 vs. -0.04 +/- 0.01 beats.min(-1).mmHg(-1) for aspirin and placebo, respectively, P < 0.05). In conclusion, these findings suggest that low dose aspirin augments CBR-HR sensitivity during concurrent muscle mechanoreflex and metaboreflex activation in healthy older humans. This increased sensitivity appears linked to reduced thromboxane sensitization of muscle mechanoreceptors, which consequently improves CBR-HR control. PMID- 26371169 TI - Neurotransmission to parasympathetic cardiac vagal neurons in the brain stem is altered with left ventricular hypertrophy-induced heart failure. AB - Hypertension, cardiac hypertrophy, and heart failure (HF) are widespread and debilitating cardiovascular diseases that affect nearly 23 million people worldwide. A distinctive hallmark of these cardiovascular diseases is autonomic imbalance, with increased sympathetic activity and decreased parasympathetic vagal tone. Recent device-based approaches, such as implantable vagal stimulators that stimulate a multitude of visceral sensory and motor fibers in the vagus nerve, are being evaluated as new therapeutic approaches for these and other diseases. However, little is known about how parasympathetic activity to the heart is altered with these diseases, and this lack of knowledge is an obstacle in the goal of devising selective interventions that can target and selectively restore parasympathetic activity to the heart. To identify the changes that occur within the brain stem to diminish the parasympathetic cardiac activity, left ventricular hypertrophy was elicited in rats by aortic pressure overload using a transaortic constriction approach. Cardiac vagal neurons (CVNs) in the brain stem that generate parasympathetic activity to the heart were identified with a retrograde tracer and studied using patch-clamp electrophysiological recordings in vitro. Animals with left cardiac hypertrophy had diminished excitation of CVNs, which was mediated both by an augmented frequency of spontaneous inhibitory GABAergic neurotransmission (with no alteration of inhibitory glycinergic activity) as well as a diminished amplitude and frequency of excitatory neurotransmission to CVNs. Opportunities to alter these network pathways and neurotransmitter receptors provide future targets of intervention in the goal to restore parasympathetic activity and autonomic balance to the heart in cardiac hypertrophy and other cardiovascular diseases. PMID- 26371170 TI - Dehydration accelerates reductions in cerebral blood flow during prolonged exercise in the heat without compromising brain metabolism. AB - Dehydration hastens the decline in cerebral blood flow (CBF) during incremental exercise, whereas the cerebral metabolic rate for O2 (CMRO2 ) is preserved. It remains unknown whether CMRO2 is also maintained during prolonged exercise in the heat and whether an eventual decline in CBF is coupled to fatigue. Two studies were undertaken. In study 1, 10 male cyclists cycled in the heat for ~2 h with (control) and without fluid replacement (dehydration) while internal and external carotid artery blood flow and core and blood temperature were obtained. Arterial and internal jugular venous blood samples were assessed with dehydration to evaluate CMRO2 . In study 2, in 8 male subjects, middle cerebral artery blood velocity was measured during prolonged exercise to exhaustion in both dehydrated and euhydrated states. After a rise at the onset of exercise, internal carotid artery flow declined to baseline with progressive dehydration (P < 0.05). However, cerebral metabolism remained stable through enhanced O2 and glucose extraction (P < 0.05). External carotid artery flow increased for 1 h but declined before exhaustion. Fluid ingestion maintained cerebral and extracranial perfusion throughout nonfatiguing exercise. During exhaustive exercise, however, euhydration delayed but did not prevent the decline in cerebral perfusion. In conclusion, during prolonged exercise in the heat, dehydration accelerates the decline in CBF without affecting CMRO2 and also restricts extracranial perfusion. Thus, fatigue is related to a reduction in CBF and extracranial perfusion rather than CMRO2 . PMID- 26371171 TI - Central-peripheral neural network interactions evoked by vagus nerve stimulation: functional consequences on control of cardiac function. AB - Using vagus nerve stimulation (VNS), we sought to determine the contribution of vagal afferents to efferent control of cardiac function. In anesthetized dogs, the right and left cervical vagosympathetic trunks were stimulated in the intact state, following ipsilateral or contralateral vagus nerve transection (VNTx), and then following bilateral VNTx. Stimulations were performed at currents from 0.25 to 4.0 mA, frequencies from 2 to 30 Hz, and a 500-MUs pulse width. Right or left VNS evoked significantly greater current- and frequency-dependent suppression of chronotropic, inotropic, and lusitropic function subsequent to sequential VNTx. Bradycardia threshold was defined as the current first required for a 5% decrease in heart rate. The threshold for the right vs. left vagus-induced bradycardia in the intact state (2.91 +/- 0.18 and 3.47 +/- 0.20 mA, respectively) decreased significantly with right VNTx (1.69 +/- 0.17 mA for right and 3.04 +/- 0.27 mA for left) and decreased further following bilateral VNTx (1.29 +/- 0.16 mA for right and 1.74 +/- 0.19 mA for left). Similar effects were observed following left VNTx. The thresholds for afferent-mediated effects on cardiac parameters were 0.62 +/- 0.04 and 0.65 +/- 0.06 mA with right and left VNS, respectively, and were reflected primarily as augmentation. Afferent-mediated tachycardias were maintained following beta-blockade but were eliminated by VNTx. The increased effectiveness and decrease in bradycardia threshold with sequential VNTx suggest that 1) vagal afferents inhibit centrally mediated parasympathetic efferent outflow and 2) the ipsilateral and contralateral vagi exert a substantial buffering capacity. The intact threshold reflects the interaction between multiple levels of the cardiac neural hierarchy. PMID- 26371172 TI - Vagal nerve stimulation activates vagal afferent fibers that reduce cardiac efferent parasympathetic effects. AB - Vagal nerve stimulation (VNS) has been shown to have antiarrhythmic effects, but many of these benefits were demonstrated in the setting of vagal nerve decentralization. The purpose of this study was to evaluate the role of afferent fiber activation during VNS on efferent control of cardiac hemodynamic and electrophysiological parameters. In 37 pigs a 56-electrode sock was placed over the ventricles to record local activation recovery intervals (ARIs), a surrogate of action potential duration. In 12 of 37 animals atropine was given systemically. Right and left VNS were performed under six conditions: both vagal trunks intact (n = 25), ipsilateral right (n = 11), ipsilateral left (n = 14), contralateral right (n = 7), contralateral left (n = 10), and bilateral (n = 25) vagal nerve transection (VNTx). Unilateral VNTx significantly affected heart rate, PR interval, Tau, and global ARIs. Right VNS after ipsilateral VNTx had augmented effects on hemodynamic parameters and increase in ARI, while subsequent bilateral VNTx did not significantly modify this effect (%change in ARI in intact condition 2.2 +/- 0.9% vs. ipsilateral VNTx 5.3 +/- 1.7% and bilateral VNTx 5.3 +/- 0.8%, P < 0.05). Left VNS after left VNTx tended to increase its effects on hemodynamics and ARI response (P = 0.07), but only after bilateral VNTx did these changes reach significance (intact 1.1 +/- 0.5% vs. ipsilateral VNTx 3.6 +/- 0.7% and bilateral VNTx 6.6 +/- 1.6%, P < 0.05 vs. intact). Contralateral VNTx did not modify VNS response. The effect of atropine on ventricular ARI was similar to bilateral VNTx. We found that VNS activates afferent fibers in the ipsilateral vagal nerve, which reflexively inhibit cardiac parasympathetic efferent electrophysiological and hemodynamic effects. PMID- 26371174 TI - Persistent change in cardiac fibroblast physiology after transient ACE inhibition. AB - Transient angiotensin-converting enzyme (ACE) inhibition induces persistent changes that protect against future nitric oxide synthase (NOS) inhibitor-induced cardiac fibrosis and inflammation. Given the role of fibroblasts in mediating these effects, the present study investigates whether prior ACE inhibition produced persistent changes in cardiac fibroblast physiology. Adult male spontaneously hypertensive rats (SHRs) were treated with vehicle (C+L) or the ACE inhibitor, enalapril (E+L) for 2 wk followed by a 2-wk washout period and a subsequent 7-day challenge with the NOS inhibitor N(omega)-nitro-l-arginine methyl ester. A third set of untreated SHRs served as controls. At the end of the study period, cardiac fibroblasts were isolated from control, C+L, and E+L left ventricles to assess proliferation rate, collagen expression, and chemokine release in vitro. After 7 days of NOS inhibition, there were areas of myocardial injury but no significant change in collagen deposition in E+L and C+L hearts in vivo. In vitro, cardiac fibroblasts isolated from C+L but not E+L hearts were hyperproliferative, demonstrated increased collagen type I gene expression, and an elevated secretion of the macrophage-recruiting chemokines monocyte chemoattractant protein-1 and granulocyte macrophage-colony stimulating factor. These findings demonstrate that in vivo N(omega)-nitro-l-arginine methyl ester treatment produces phenotypic changes in fibroblasts that persist in vitro. Moreover, this is the first demonstration that transient ACE inhibition can produce a persistent modification of the cardiac fibroblast phenotype to one that is less inflammatory and fibrogenic. It may be that the cardioprotective effects of ACE inhibition are related in part to beneficial changes in cardiac fibroblast physiology. PMID- 26371175 TI - Pregnancy-induced remodeling of heart valves. AB - Recent studies have demonstrated remodeling of aortic and mitral valves leaflets under the volume loading and cardiac expansion of pregnancy. Those valves' leaflets enlarge with altered collagen fiber architecture, content, and cross linking and biphasic changes (decreases, then increases) in extensibility during gestation. This study extends our analyses to right-sided valves, with additional compositional measurements for all valves. Valve leaflets were harvested from nonpregnant heifers and pregnant cows. Leaflet structure was characterized by leaflet dimensions, and ECM composition was determined using standard biochemical assays. Histological studies assessed changes in cellular and ECM components. Leaflet mechanical properties were assessed using equibiaxial mechanical testing. Collagen thermal stability and cross-linking were assessed using denaturation and hydrothermal isometric tension tests. Pulmonary and tricuspid leaflet areas increased during pregnancy by 35 and 55%, respectively. Leaflet thickness increased by 20% only in the pulmonary valve and largely in the fibrosa (30% thickening). Collagen crimp length was reduced in both the tricuspid (61%) and pulmonary (42%) valves, with loss of crimped area in the pulmonary valve. Thermomechanics showed decreased collagen thermal stability with surprisingly maintained cross-link maturity. The pulmonary leaflet exhibited the biphasic change in extensibility seen in left side valves, whereas the tricuspid leaflet mechanics remained largely unchanged throughout pregnancy. The tricuspid valve exhibits a remodeling response during pregnancy that is significantly diminished from the other three valves. All valves of the heart remodel in pregnancy in a manner distinct from cardiac pathology, with much similarity valve to valve, but with interesting valve-specific responses in the aortic and tricuspid valves. PMID- 26371173 TI - The stress of maternal separation causes misprogramming in the postnatal maturation of rat resistance arteries. AB - We examined the effect of stress in the first 2 wk of life induced by brief periods of daily maternal separation on developmental programming of rat small resistance mesenteric arteries (MAs). In MAs of littermate controls, mRNAs encoding mediators of vasoconstriction, including the alpha1a-adrenergic receptor, smooth muscle myosin heavy chain, and CPI-17, the inhibitory subunit of myosin phosphatase, increased from after birth through sexual [postnatal day (PND) 35] and full maturity, up to ~80-fold, as measured by quantitative PCR. This was commensurate with two- to fivefold increases in maximum force production to KCl depolarization, calcium, and the alpha-adrenergic agonist phenylephrine, and increasing systolic blood pressure. Rats exposed to maternal separation stress as neonates had markedly accelerated trajectories of maturation of arterial contractile gene expression and function measured at PND14 or PND21 (weaning), 1 wk after the end of the stress protocol. This was suppressed by the alpha-adrenergic receptor blocker terazosin (0.5 mg.kg ip(-1).day(-1)), indicating dependence on stress activation of sympathetic signaling. Due to the continued maturation of MAs in control rats, by sexual maturity (PND35) and into adulthood, no differences were observed in arterial function or response to a second stressor in rats stressed as neonates. Thus early life stress misprograms resistance artery smooth muscle, increasing vasoconstrictor function and blood pressure. This effect wanes in later stages, suggesting plasticity during arterial maturation. Further studies are indicated to determine whether stress in different periods of arterial maturation may cause misprogramming persisting through maturity and the potential salutary effect of alpha-adrenergic blockade in suppression of this response. PMID- 26371176 TI - HDACs Regulate miR-133a Expression in Pressure Overload-Induced Cardiac Fibrosis. AB - BACKGROUND: MicroRNAs (miRNAs) and histone deacetylases (HDACs) serve a significant role in the pathogenesis of a variety of cardiovascular diseases. The transcriptional regulation of miRNAs is poorly understood in cardiac hypertrophy. We investigated whether the expression of miR-133a is epigenetically regulated by class I and IIb HDACs during hypertrophic remodeling. METHODS AND RESULTS: Transverse aortic constriction (TAC) was performed in CD1 mice to induce pressure overload hypertrophy. Mice were treated with class I and IIb HDAC inhibitor (HDACi) via drinking water for 2 and 4 weeks post TAC. miRNA expression was determined by real-time polymerase chain reaction. Echocardiography was performed at baseline and post TAC end points for structural and functional assessment. Chromatin immunoprecipitation was used to identify HDACs and transcription factors associated with miR-133a promoter. miR-133a expression was downregulated by 0.7- and 0.5-fold at 2 and 4 weeks post TAC, respectively, when compared with vehicle control (P<0.05). HDAC inhibition prevented this significant decrease 2 weeks post TAC and maintained miR-133a expression near vehicle control levels, which coincided with (1) a decrease in connective tissue growth factor expression, (2) a reduction in cardiac fibrosis and left atrium diameter (marker of end-diastolic pressure), suggesting an improvement in diastolic function. Chromatin immunoprecipitation analysis revealed that HDAC1 and HDAC2 are present on the miR-133a enhancer regions. CONCLUSIONS: The results reveal that HDACs play a role in the regulation of pressure overload-induced miR-133a downregulation. This work is the first to provide insight into an epigenetic-miRNA regulatory pathway in pressure overload-induced cardiac fibrosis. PMID- 26371177 TI - The levonorgestrel-releasing intrauterine system is associated with delayed endocervical clearance of Chlamydia trachomatis without alterations in vaginal microbiota. AB - Progestin-based contraception may impact women's susceptibility to sexually transmitted infection. We evaluated the effect of the levonorgestrel intrauterine system (LNG-IUS) on cervical persistence of Chlamydia trachomatis (CT) in a baboon model. Female olive baboons (Papio anubis) with or without an LNG-IUS received CT or sham inoculations. CT was detected in cervical epithelium with weekly nucleic acid amplification testing (NAAT) and culture. Presence of the LNG IUS was associated with prolonged persistence of CT. Median time to post inoculation clearance of CT as detected by NAAT was 10 weeks (range 7-12) for animals with an LNG-IUS and 3 weeks (range 0-12) for non-LNG-IUS animals (P = 0.06). Similarly, median time to post-inoculation clearance of CT by culture was 9 weeks (range 3-12) for LNG-IUS animals and 1.5 weeks (range 0-10) for non-LNG IUS animals (P = 0.04). We characterized the community structure of the vaginal microbiota with the presence of the LNG-IUS to determine if alterations in CT colonization dynamics were associated with changes in vaginal commensal bacteria. Vaginal swabs were collected weekly for microbiome analysis. Endocervical CT infection was not correlated with alterations in the vaginal microbiota. Together, these results suggest that LNG-IUS may facilitate CT endocervical persistence through a mechanism distinct from vaginal microbial alterations. PMID- 26371178 TI - Waning and aging of cellular immunity to Bordetella pertussis. AB - While it is clear that the maintenance of Bordetella pertussis-specific immunity evoked both after vaccination and infection is insufficient, it is unknown at which pace waning occurs and which threshold levels of sustained functional memory B and T cells are required to provide long-term protection. Longevity of human cellular immunity to B. pertussis has been studied less extensively than serology, but is suggested to be key for the observed differences between the duration of protection induced by acellular vaccination and whole cell vaccination or infection. The induction and maintenance of levels of protective memory B and T cells may alter with age, associated with changes of the immune system throughout life and with accumulating exposures to circulating B. pertussis or vaccine doses. This is relevant since pertussis affects all age groups. This review summarizes current knowledge on the waning patterns of human cellular immune responses to B. pertussis as addressed in diverse vaccination and infection settings and in various age groups. Knowledge on the effectiveness and flaws in human B. pertussis-specific cellular immunity ultimately will advance the improvement of pertussis vaccination strategies. PMID- 26371179 TI - Residence in biofilms allows Burkholderia cepacia complex (Bcc) bacteria to evade the antimicrobial activities of neutrophil-like dHL60 cells. AB - Bacteria of the Burkholderia cepacia complex (Bcc) persist in the airways of people with cystic fibrosis (CF) despite the continuous recruitment of neutrophils. Most members of Bcc are multidrug resistant and can form biofilms. As such, we sought to investigate whether biofilm formation plays a role in protecting Bcc bacteria from neutrophils. Using the neutrophil-like, differentiated cell line, dHL60, we have shown for the first time that Bcc biofilms are enhanced in the presence of these cells. Biofilm biomass was greater following culture in the presence of dHL60 cells than in their absence, likely the result of incorporating dHL60 cellular debris into the biofilm. Moreover, we have demonstrated that mature biofilms (cultured for up to 72 h) induced necrosis in the cells. Established biofilms also acted as a barrier to the migration of the cells and masked the bacteria from being recognized by the cells; dHL60 cells expressed less IL-8 mRNA and secreted significantly less IL-8 when cultured in the presence of biofilms, with respect to planktonic bacteria. Our findings provide evidence that biofilm formation can, at least partly, enable the persistence of Bcc bacteria in the CF airway and emphasize a requirement for anti biofilm therapeutics. PMID- 26371181 TI - Sympathetic Reinnervation Is Required for Mammalian Cardiac Regeneration. AB - RATIONALE: Although mammalian cardiac regeneration can occur in the neonatal period, the factors involved in this process remain to be established. Because tissue and limb regeneration require concurrent reinnervation by the peripheral nervous system, we hypothesized that cardiac regeneration also requires reinnervation. OBJECTIVE: To test the hypothesis that reinnervation is required for innate neonatal cardiac regeneration. METHODS AND RESULTS: We crossed a Wnt1 Cre transgenic mouse with a double-tandem Tomato reporter strain to identify neural crest-derived cell lineages including the peripheral autonomic nerves in the heart. This approach facilitated the precise visualization of subepicardial autonomic nerves in the ventricles using whole mount epifluorescence microscopy. After resection of the left ventricular apex in 2-day-old neonatal mice, sympathetic nerve structures, which envelop the heart under normal conditions, exhibited robust regrowth into the regenerating myocardium. Chemical sympathectomy inhibited sympathetic regrowth and subsequent cardiac regeneration after apical resection significantly (scar size as cross-sectional percentage of viable left ventricular myocardium, n=9; 0.87%+/-1.4% versus n=6; 14.05+/-4.4%; P<0.01). CONCLUSIONS: These findings demonstrate that the profound regenerative capacity of the neonatal mammalian heart requires sympathetic innervation. As such, these data offer significant insights into an underlying basis for inadequate adult regeneration after myocardial infarction, a situation where nerve growth is hindered by age-related influences and scar tissue. PMID- 26371182 TI - Structural Basis for Inhibition of Human Autotaxin by Four Potent Compounds with Distinct Modes of Binding. AB - Autotaxin (ATX) is a secreted enzyme that hydrolyzes lysophosphatidylcholine to lysophosphatidic acid (LPA). LPA is a bioactive phospholipid that regulates diverse biological processes, including cell proliferation, migration, and survival/apoptosis, through the activation of a family of G protein-coupled receptors. The ATX-LPA pathway has been implicated in many pathologic conditions, including cancer, fibrosis, inflammation, cholestatic pruritus, and pain. Therefore, ATX inhibitors represent an attractive strategy for the development of therapeutics to treat a variety of diseases. Mouse and rat ATX have been crystallized previously with LPA or small-molecule inhibitors bound. Here, we present the crystal structures of human ATX in complex with four previously unpublished, structurally distinct ATX inhibitors. We demonstrate that the mechanism of inhibition of each compound reflects its unique interactions with human ATX. Our studies may provide a basis for the rational design of novel ATX inhibitors. PMID- 26371184 TI - Suicidal Risks in Reports of Long-Term Treatment Trials for Major Depressive Disorder. PMID- 26371183 TI - The Role of Ephs and Ephrins in Memory Formation. AB - The ability to efficiently store memories in the brain is a fundamental process and its impairment is associated with multiple human mental disorders. Evidence indicates that long-term memory formation involves alterations of synaptic efficacy produced by modifications in neural transmission and morphology. The Eph receptors and their cognate ephrin ligands have been shown to be involved in these key neuronal processes by regulating events such as presynaptic transmitter release, postsynaptic glutamate receptor conductance and trafficking, synaptic glutamate reuptake, and dendritic spine morphogenesis. Recent findings show that Ephs and ephrins are needed for memory formation in different organisms. These proteins participate in the formation of various types of memories that are subserved by different neurons and brain regions. Ephs and ephrins are involved in brain disorders and diseases with memory impairment symptoms, including Alzheimer's disease and anxiety. Drugs that agonize or antagonize Ephs/ephrins signaling have been developed and could serve as therapeutic agents to treat such diseases. Ephs and ephrins may therefore induce cellular alterations mandatory for memory formation and serve as a target for pharmacological intervention for treatment of memory-related brain diseases. PMID- 26371185 TI - Deletion of CTLA-4 on regulatory T cells during adulthood leads to resistance to autoimmunity. AB - Cytotoxic T lymphocyte antigen-4 (CTLA-4) is an essential negative regulator of T cell responses. Germline Ctla4 deficiency is lethal, making investigation of the function of CTLA-4 on mature T cells challenging. To elucidate the function of CTLA-4 on mature T cells, we have conditionally ablated Ctla4 in adult mice. We show that, in contrast to germline knockout mice, deletion of Ctla4 during adulthood does not precipitate systemic autoimmunity, but surprisingly confers protection from experimental autoimmune encephalomyelitis (EAE) and does not lead to increased resistance to MC38 tumors. Deletion of Ctla4 during adulthood was accompanied by activation and expansion of both conventional CD4(+)Foxp3(-) (T conv) and regulatory Foxp3(+) (T reg cells) T cell subsets; however, deletion of CTLA-4 on T reg cells was necessary and sufficient for protection from EAE. CTLA 4 deleted T reg cells remained functionally suppressive. Deletion of Ctla4 on T reg cells alone or on all adult T cells led to major changes in the Ctla4 sufficient T conv cell compartment, including up-regulation of immunoinhibitory molecules IL-10, LAG-3 and PD-1, thereby providing a compensatory immunosuppressive mechanism. Collectively, our findings point to a profound role for CTLA-4 on T reg cells in limiting their peripheral expansion and activation, thereby regulating the phenotype and function of T conv cells. PMID- 26371186 TI - Altered BCR and TLR signals promote enhanced positive selection of autoreactive transitional B cells in Wiskott-Aldrich syndrome. AB - Wiskott-Aldrich syndrome (WAS) is an X-linked immunodeficiency disorder frequently associated with systemic autoimmunity, including autoantibody-mediated cytopenias. WAS protein (WASp)-deficient B cells have increased B cell receptor (BCR) and Toll-like receptor (TLR) signaling, suggesting that these pathways might impact establishment of the mature, naive BCR repertoire. To directly investigate this possibility, we evaluated naive B cell specificity and composition in WASp-deficient mice and WAS subjects (n = 12). High-throughput sequencing and single-cell cloning analysis of the BCR repertoire revealed altered heavy chain usage and enrichment for low-affinity self-reactive specificities in murine marginal zone and human naive B cells. Although negative selection mechanisms including deletion, anergy, and receptor editing were relatively unperturbed, WASp-deficient transitional B cells showed enhanced proliferation in vivo mediated by antigen- and Myd88-dependent signals. Finally, using both BCR sequencing and cell surface analysis with a monoclonal antibody recognizing an intrinsically autoreactive heavy chain, we show enrichment in self reactive cells specifically at the transitional to naive mature B cell stage in WAS subjects. Our combined data support a model wherein modest alterations in B cell-intrinsic, BCR, and TLR signals in WAS, and likely other autoimmune disorders, are sufficient to alter B cell tolerance via positive selection of self-reactive transitional B cells. PMID- 26371188 TI - The microRNA-212/132 cluster regulates B cell development by targeting Sox4. AB - MicroRNAs have emerged as key regulators of B cell fate decisions and immune function. Deregulation of several microRNAs in B cells leads to the development of autoimmune disease and cancer in mice. We demonstrate that the microRNA 212/132 cluster (miR-212/132) is induced in B cells in response to B cell receptor signaling. Enforced expression of miR-132 results in a block in early B cell development at the prepro-B cell to pro-B cell transition and induces apoptosis in primary bone marrow B cells. Importantly, loss of miR-212/132 results in accelerated B cell recovery after antibody-mediated B cell depletion. We find that Sox4 is a target of miR-132 in B cells. Co-expression of SOX4 with miR-132 rescues the defect in B cell development from overexpression of miR-132 alone, thus suggesting that miR-132 may regulate B lymphopoiesis through Sox4. In addition, we show that the expression of miR-132 can inhibit cancer development in cells that are prone to B cell cancers, such as B cells expressing the c-Myc oncogene. We have thus uncovered miR-132 as a novel contributor to B cell development. PMID- 26371189 TI - A 6-Year-Old With Leg Cramps. AB - A 6-year-old girl presented with a history of leg pain and cramping that progressively worsened over a 2- to 3-week period of time. Her examination was notable for normal vital signs, limited range of motion of her left hip, and a limp. Inflammatory markers were slightly elevated, but the serum electrolytes, calcium, and magnesium, complete blood cell count and differential, and creatine kinase level were normal. She was hospitalized for further diagnostic evaluation and was noted to have abnormal muscle movements classified as myokymia (continuous involuntary quivering, rippling, or undulating movement of muscles). Electromyography confirmed the myokymia but did not reveal evidence of a myopathy or neuropathy, prompting additional evaluation for a systemic etiology. PMID- 26371187 TI - Epithelial-intrinsic IKKalpha expression regulates group 3 innate lymphoid cell responses and antibacterial immunity. AB - Innate lymphoid cells (ILCs) are critical for maintaining epithelial barrier integrity at mucosal surfaces; however, the tissue-specific factors that regulate ILC responses remain poorly characterized. Using mice with intestinal epithelial cell (IEC)-specific deletions in either inhibitor of kappaB kinase (IKK)alpha or IKKbeta, two critical regulators of NFkappaB activation, we demonstrate that IEC intrinsic IKKalpha expression selectively regulates group 3 ILC (ILC3)-dependent antibacterial immunity in the intestine. Although IKKbeta(DeltaIEC) mice efficiently controlled Citrobacter rodentium infection, IKKalpha(DeltaIEC) mice exhibited severe intestinal inflammation, increased bacterial dissemination to peripheral organs, and increased host mortality. Consistent with weakened innate immunity to C. rodentium, IKKalpha(DeltaIEC) mice displayed impaired IL-22 production by RORgammat(+) ILC3s, and therapeutic delivery of rIL-22 or transfer of sort-purified IL-22-competent ILCs from control mice could protect IKKalpha(DeltaIEC) mice from C. rodentium-induced morbidity. Defective ILC3 responses in IKKalpha(DeltaIEC) mice were associated with overproduction of thymic stromal lymphopoietin (TSLP) by IECs, which negatively regulated IL-22 production by ILC3s and impaired innate immunity to C. rodentium. IEC-intrinsic IKKalpha expression was similarly critical for regulation of intestinal inflammation after chemically induced intestinal damage and colitis. Collectively, these data identify a previously unrecognized role for epithelial cell-intrinsic IKKalpha expression and TSLP in regulating ILC3 responses required to maintain intestinal barrier immunity. PMID- 26371190 TI - Disclosure of Genome Sequencing Results: Are Pediatricians Ready? PMID- 26371191 TI - Professionally Responsible Disclosure of Genomic Sequencing Results in Pediatric Practice. AB - Genomic sequencing is being rapidly introduced into pediatric clinical practice. The results of sequencing are distinctive for their complexity and subsequent challenges of interpretation for generalist and specialist pediatricians, parents, and patients. Pediatricians therefore need to prepare for the professionally responsible disclosure of sequencing results to parents and patients and guidance of parents and patients in the interpretation and use of these results, including managing uncertain data. This article provides an ethical framework to guide and evaluate the professionally responsible disclosure of the results of genomic sequencing in pediatric practice. The ethical framework comprises 3 core concepts of pediatric ethics: the best interests of the child standard, parental surrogate decision-making, and pediatric assent. When recommending sequencing, pediatricians should explain the nature of the proposed test, its scope and complexity, the categories of results, and the concept of a secondary or incidental finding. Pediatricians should obtain the informed permission of parents and the assent of mature adolescents about the scope of sequencing to be performed and the return of results. PMID- 26371192 TI - Febrile Seizures After 2010-2011 Trivalent Inactivated Influenza Vaccine. AB - OBJECTIVES: In the Post-Licensure Rapid Immunization Safety Monitoring Program, we examined risk of febrile seizures (FS) after trivalent inactivated influenza vaccine (TIV) and 13-valent pneumococcal conjugate vaccine (PCV13) during the 2010-2011 influenza season, adjusted for concomitant diphtheria tetanus acellular pertussis-containing vaccines (DTaP). Assuming children would receive both vaccines, we examined whether same-day TIV and PCV13 vaccination was associated with greater FS risk when compared with separate-day vaccination. METHODS: We used a self-controlled risk interval design, comparing the FS rate in a risk interval (0-1 days) versus control interval (14-20 days). Vaccinations were identified in claims and immunization registry data. FS were confirmed with medical records. RESULTS: No statistically significant TIV-FS associations were found in unadjusted or adjusted models (incidence rate ratio [IRR] adjusted for age, seasonality, and concomitant PCV13 and DTaP: 1.36, 95% confidence interval [CI] 0.78 to 2.39). Adjusted for age and seasonality, PCV13 was significantly associated with FS (IRR 1.74, 95% CI 1.06 to 2.86), but not when further adjusting for concomitant TIV and DTaP (IRR 1.61, 95% CI 0.91 to 2.82). Same-day TIV and PCV13 vaccination was not associated with excess risk of FS when compared with separate-day vaccination (1.08 fewer FS per 100 000 with same day administration, 95% CI -5.68 to 6.09). CONCLUSIONS: No statistically significant increased risk of FS was found for 2010-2011 TIV or PCV13, when adjusting for concomitant vaccines. Same-day TIV and PCV13 vaccination was not associated with more FS compared with separate-day vaccination. PMID- 26371193 TI - Providing Psychosocial Support to Children and Families in the Aftermath of Disasters and Crises. AB - Disasters have the potential to cause short- and long-term effects on the psychological functioning, emotional adjustment, health, and developmental trajectory of children. This clinical report provides practical suggestions on how to identify common adjustment difficulties in children in the aftermath of a disaster and to promote effective coping strategies to mitigate the impact of the disaster as well as any associated bereavement and secondary stressors. This information can serve as a guide to pediatricians as they offer anticipatory guidance to families or consultation to schools, child care centers, and other child congregate care sites. Knowledge of risk factors for adjustment difficulties can serve as the basis for mental health triage. The importance of basic supportive services, psychological first aid, and professional self-care are discussed. Stress is intrinsic to many major life events that children and families face, including the experience of significant illness and its treatment. The information provided in this clinical report may, therefore, be relevant for a broad range of patient encounters, even outside the context of a disaster. Most pediatricians enter the profession because of a heartfelt desire to help children and families most in need. If adequately prepared and supported, pediatricians who are able to draw on their skills to assist children, families, and communities to recover after a disaster will find the work to be particularly rewarding. PMID- 26371194 TI - Tricycle Injuries Presenting to US Emergency Departments, 2012-2013. AB - OBJECTIVE: To investigate the characteristics of tricycle-related injuries in children presenting to US emergency departments (EDs). METHODS: Data regarding tricycle injuries in children younger than 18 years of age were obtained from the National Electronic Injury Surveillance System for calendar years 2012 and 2013. Data included body regions injured, ED disposition, and demographics. RESULTS: There were an estimated 9340 tricycle-related injuries treated in US EDs from 2012 to 2013. The average age was 3 years. Children 2 years of age had the highest frequency of injuries. Boys accounted for 63.6% of all injuries. Children 1 to 2 years of age represented 51.9% of all injuries. Lacerations were the most common type of injury. Internal organ damage was the most common type of injury in 3- and 5-year-olds. Contusions were the most common type of injury in 1- and 7 year-olds. The head was the most commonly injured region of the body and the most common region to endure internal damage. The elbows were the most commonly fractured body part. The upper extremity was more frequently fractured than the lower extremity. Approximately 2.4% of all injured children were admitted to the hospital. CONCLUSIONS: The upper extremity of children, particularly the elbow, was more frequently fractured than the lower extremity. The head was the most common body part to endure internal damage. By elucidating the characteristics of tricycle-related injuries, preventive measures can be implemented to decrease the incidence of tricycle-related injuries and ED visits. PMID- 26371195 TI - Residential Exposure to Pesticide During Childhood and Childhood Cancers: A Meta Analysis. AB - CONTEXT: There is an increasing concern about chronic low-level pesticide exposure during childhood and its influence on childhood cancers. OBJECTIVE: In this meta-analysis, we aimed to examine associations between residential childhood pesticide exposures and childhood cancers. DATA SOURCES: We searched all observational studies published in PubMed before February 2014 and reviewed reference sections of articles derived from searches. STUDY SELECTION: The literature search yielded 277 studies that met inclusion criteria. DATA EXTRACTION: Sixteen studies were included in the meta-analysis. We calculated effect sizes and 95% confidence intervals (CIs) by using a random effect model with inverse variance weights. RESULTS: We found that childhood exposure to indoor but not outdoor residential insecticides was associated with a significant increase in risk of childhood leukemia (odds ratio [OR] = 1.47; 95% CI, 1.26 1.72; I(2) = 30%) and childhood lymphomas (OR = 1.43; 95% CI, 1.15-1.78; I(2) = 0%). A significant increase in risk of leukemia was also associated with herbicide exposure (OR = 1.26; 95% CI, 1.10-1.44; I(2) = 0%). Also observed was a positive but not statistically significant association between childhood home pesticide or herbicide exposure and childhood brain tumors. LIMITATIONS: The small number of studies included in the analysis represents a major limitation of the current analysis. CONCLUSIONS: Results from this meta-analysis indicated that children exposed to indoor insecticides would have a higher risk of childhood hematopoietic cancers. Additional research is needed to confirm the association between residential indoor pesticide exposures and childhood cancers. Meanwhile, preventive measures should be considered to reduce children's exposure to pesticides at home. PMID- 26371196 TI - Implementation of a Neonatal Abstinence Syndrome Weaning Protocol: A Multicenter Cohort Study. AB - OBJECTIVES: To evaluate the generalizability of stringent protocol-driven weaning in improving total duration of opioid treatment and length of inpatient hospital stay after treatment of neonatal abstinence syndrome (NAS). METHODS: We conducted a retrospective cohort analysis of 981 infants who completed pharmacologic treatment of NAS with methadone or morphine from January 2012 through August 2014. Before July 2013, 3 of 6 neonatology provider groups (representing Ohio's 6 children's hospitals) directed NAS nursery care by using group-specific treatment protocols containing explicit weaning guidelines. In July 2013, a standardized weaning protocol was adopted by all 6 groups. Statistical analysis was performed to identify effects of adoption of the multicenter weaning protocol on total duration of opioid treatment and length of hospital stay at the protocol-adopting sites and at the sites with preexisting protocol-driven weaning. RESULTS: After adoption of the multicenter protocol, infants treated by the 3 groups previously without stringent weaning guidelines experienced shorter duration of opioid treatment (23.0 vs 34.0 days, P < .001) and length of inpatient hospital stay (23.7 vs 31.6 days, P < .001). Protocol-adopting sites also experienced a lower rate of adjunctive drug therapy (5% vs 21%, P = .004). Outcomes were sustained by the 3 groups who initially had specific weaning guidelines after multicenter adoption (duration of treatment = 17.0 days and length of hospital stay = 23.3 days). CONCLUSIONS: Adoption of a stringent weaning protocol resulted in improved NAS outcomes, demonstrating generalizability of the protocol-driven weaning approach. Opportunity remains for additional protocol refinement. PMID- 26371197 TI - Reasons for Rehospitalization in Children Who Had Neonatal Abstinence Syndrome. AB - BACKGROUND AND OBJECTIVES: Neonatal abstinence syndrome (NAS) occurs after in utero exposure to opioids, but outcomes after the postnatal period are unclear. Our objectives were to characterize childhood hospitalization after NAS. METHODS: Population-based linkage study of births, hospitalization, and death records of all children registered in New South Wales (NSW), Australia, between 2000 and 2011 to a maximum of 13 years. Infants with an International Statistical Classification of Disease and Related Problems, 10th Edition, Australian Modification, coding of NAS (P96.1, n = 3842) were compared with 1,018,421 live born infants without an NAS diagnosis. RESULTS: Infants with NAS were more likely to be admitted into a nursery (odds ratio 15.6, 95% confidence interval: 14.5 16.8) and be hospitalized longer (10.0 vs 3.0 days). In childhood, they were more likely to be rehospitalized (1.6, 1.5-1.7), die during hospitalization (3.3, 2.1 5.1), and be hospitalized for assaults (15.2, 11.3-20.6), maltreatment (21.0, 14.3-30.9), poisoning (3.6, 2.6-4.8), and mental/behavioral (2.6, 2.1-3.2) and visual (2.9, 2.5-3.5) disorders. Mothers of infants with NAS were more likely to be Indigenous (6.4, 6.0-7.0), have no antenatal care (6.6, 5.9-7.4), and be socioeconomically deprived (1.6, 1.5-1.7). Regression analyses demonstrated that NAS was the most important predictor of admissions for maltreatment (odds ratio 4.5, 95% confidence interval: 3.4-6.1) and mental and behavioral disorders (2.3, 1.9-2.9), even after accounting for prematurity, maternal age, and Indigenous status. CONCLUSIONS: Children with NAS are more likely to be rehospitalized during childhood for maltreatment, trauma, and mental and behavioral disorders even after accounting for prematurity. This continues to adolescence and emphasizes the critical need for continued support of this vulnerable group after resolution of NAS. PMID- 26371198 TI - Timing of the Diagnosis of Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder. AB - BACKGROUND AND OBJECTIVE: Symptoms of inattention, hyperactivity, and impulsivity are core features of attention-deficit/hyperactivity disorder (ADHD). However, children with autism spectrum disorder (ASD) often present with similar symptoms and may receive a diagnosis of ADHD first. We investigated the relationship between the timing of ADHD diagnosis in children with ASD and the age at ASD diagnosis. METHODS: Data were drawn from the 2011-2012 National Survey of Children's Health, which asked parents to provide the age(s) at which their child received a diagnosis of ADHD and/or ASD. Using weighted prevalence estimates, we examined the association between a previous diagnosis of ADHD and the age at ASD diagnosis, while controlling for factors known to influence the timing of ASD diagnosis. RESULTS: Our study consisted of 1496 children with a current diagnosis of ASD as reported by parents of children ages 2 to 17 years. Approximately 20% of these children had initially been diagnosed with ADHD. Children diagnosed with ADHD before ASD were diagnosed with ASD ~3 years (95% confidence interval 2.3 3.5) after children in whom ADHD was diagnosed at the same time or after ASD. The children with ADHD diagnosed first were nearly 30 times more likely to receive their ASD diagnosis after age 6 (95% confidence interval 11.2-77.8). The delay in ASD diagnosis was consistent across childhood and independent of ASD severity. CONCLUSION: To avoid potential delays in ASD diagnosis, clinicians should consider ASD in young children presenting with ADHD symptoms. PMID- 26371199 TI - Effects of Genotype and Sleep on Temperament. AB - BACKGROUND AND OBJECTIVES: Sleep problems are frequent in young children; however, children vary in the degree to which they are affected by poor sleep quality. We investigated whether a polymorphism in the serotonin transporter gene, which is linked to emotional function, is a potential moderator of the influences of sleep duration on infant temperament using longitudinal data. METHODS: We examined the interactive effects of average sleep duration between 6 and 36 months of age and the 5-HTTLPR genotype on negative emotionality/behavioral dysregulation at 36 months in 209 children recruited into a longitudinal birth cohort study. Triallelic genotyping of 5-HTTLPR was performed by looking at SLC6A4 genotype, focusing on the serotonin transporter linked polymorphic region (5-HTTLPR) including the SNP polymorphism (rs23351). Child sleep habits were assessed with a maternal self-report questionnaire. RESULTS: After controlling for demographics and both previous and concurrent maternal depression, multiple linear regression analyses revealed a significant interaction effect of average sleep duration for the first 3 years of life and 5 HTTLPR genotype on child negative emotionality/behavioral dysregulation such that the effects were exclusive to those with low-expressing 5-HTTLPR genotypes. CONCLUSIONS: The results suggest differential susceptibility to the effect of sleep duration early in life, which reiterates that the short allele of the 5 HTTLPR represents a marker of increased environmental sensitivity regarding emotional development. Differential susceptibility theory posits that certain factors may increase an individual's susceptibility to the environment, in either a positive or negative fashion. PMID- 26371200 TI - Introduction: State-of-the-Art on Child Health Disparities. PMID- 26371201 TI - Treating Children With Cancer Worldwide--Challenges and Interventions. PMID- 26371202 TI - Sudden Infant Death With Area Postrema Lesion Likely Due to Wrong Use of Insecticide. AB - We report a noteworthy case of a 7-month-old infant who suddenly and unexpectedly died during her sleep. After a complete postmortem examination, review of the clinical history, and detailed death scene investigation, the death remained unexplained, leading to a diagnosis of sudden infant death syndrome. However, an extensive review of the brainstem neuropathology revealed a severe alteration in the area postrema (a highly vascular structure lying at the base of the fourth ventricle outside of the blood-brain barrier). The alteration was likely due to massive and repeated to a common household insecticide in the last few weeks of life. These results provide an explanation for this sudden infant death, allowing a differential diagnosis from sudden infant death syndrome. PMID- 26371203 TI - Family Experience and PICU Death: A Meta-Synthesis. AB - BACKGROUND AND OBJECTIVES: The PICU is the most common site for inpatient pediatric deaths worldwide. The impact of this clinical context on family experiences of their child's death is unclear. The objective of the study was to review and synthesize the best available evidence exploring the family experience of the death of their child in the PICU. METHODS: Studies were retrieved from CINAHL Plus, OVID Medline, Scopus, PsycINFO, and Embase. Gray literature was retrieved from greylit.com, opengrey.edu, Trove, Worldcat, and Google scholar. Study selection was undertaken by 4 reviewers by using a multistep screening process, based on a previously developed protocol (International Prospective Register of Systematic Reviews 2015:CRD42015017463). Data was extracted as first order constructs (direct quotes) or second-order constructs (author interpretations) onto a predeveloped extraction tool. Data were analyzed by thematic synthesis. RESULTS: One main theme and 3 subthemes emerged. "Reclaiming parenthood" encompasses the ways in which the parental role is threatened when a child is dying in the PICU, with the subthemes "Being a parent in the PICU," "Being supported," and "Parenting after death" elucidating the ways parents work to reclaim this role. The review is limited by a language bias, and by the limitations of the primary studies. CONCLUSIONS: When a child dies in a PICU, many aspects of the technology, environment, and staff actions present a threat to the parental role both during and after the child's death. Reclaiming this role requires support from health care providers and the wider community. PMID- 26371204 TI - Interpregnancy Interval and Risk of Autism Spectrum Disorders. AB - OBJECTIVE: To determine whether subsequent births after short and long interpregnancy intervals (IPIs) are associated with risk of autism spectrum disorder (ASD). METHOD: We assessed the association between IPI and ASD risk in a cohort of 45 261 children born at Kaiser Permanente Northern California (KPNC) between 2000 and 2009. Children with ASD were identified from International Classification of Diseases, Revision 9 diagnostic codes 299.0, 299.8, and 299.9 recorded in KPNC electronic medical records. IPI was defined as the time from the birth of the first child to the conception of the second child. Survival analysis and logistic regression models were used to evaluate the association between IPI and risk of ASD in second-born children. RESULTS: Children born after an IPI of <12 months or >=72 months had a 2- to 3-fold increased ASD risk compared with children born after an interval of 36 to 47 months. Respective adjusted hazard ratios (95% confidence intervals) were as follows: <6 months, 3.0 (1.9-4.7); 6 to 8 months, 2.1 (1.4-3.3); 9 to 11 months, 1.9 (1.3-2.1); 12 to 23 months, 1.5 (1.1 2.1); and >=72 months, 2.4 (1.5-3.7). The results are not explained by maternal BMI or change in BMI between pregnancies or by parental age, maternal antidepressant medication use, or unfavorable events occurring during the first or second pregnancy. CONCLUSIONS: Children born after interpregnancy intervals <2 years or >6 years may be at increased risk of ASD. The mechanism explaining this association is unknown, and more research is needed. PMID- 26371205 TI - Are Pediatricians Complicit in Vitamin K Deficiency Bleeding? AB - The American Academy of Pediatrics recommends that all newborns receive a single dose of intramuscular vitamin K to prevent vitamin K deficiency bleeding. How should the clinician respond when parents decline vitamin K? Although vitamin K deficiency bleeding can have devastating sequelae, they are uncommon; therefore, parents are generally allowed to decline vitamin K after counseling is provided. When parents ask for a vitamin K preparation of unproven effectiveness, should the clinician honor that request? To address these questions, we present a case of a healthy newborn whose parents declined intramuscular vitamin K and requested an oral preparation. Two general pediatricians discuss the medical and ethical issues these situations pose, and the parents describe their experience. PMID- 26371206 TI - Exposomics: mathematics meets biology. AB - Although 'exposome' research has started to appear, and the concept is fascinating, we still have little proof-of-principle. This issue of Mutagenesis reports a few examples of exposome research, showing that the approach is providing the first results. In this Commentary, I develop the example of epigenome-wide methylation studies related to smoking as a success story, that fits well with previous research in humans and in vitro on mechanisms of carcinogenesis, and also with conceptual models such as Cairns' model based on asymmetric division of stem cells. The field of exposomics merges different disciplines, notably biology and mathematics, but also the evolutionary theory, and can possibly lead to interesting breakthroughs in the next years. PMID- 26371207 TI - Caregiving reduces mortality risk for most caregivers: a census-based record linkage study. AB - BACKGROUND: Countries with advanced welfare systems are increasingly relying on the input of informal caregivers, and there are growing concerns for their mental and physical wellbeing. However, the evidence about the relationship between caregiving and mortality risk is less clear. METHODS: A census-based record linkage study with mortality follow-up of 33 months: participants totalled 1 122 779 individuals including 183 842 caregivers, of whom 28.2% (51 927) were providing 50 or more hours caregiving per week. RESULTS: Over 33 months of follow up a total of 29 335 deaths occurred, 2443 of these among caregivers. Mortality risk for caregivers was lower than for non-caregivers [hazard ratio (HR) = 0.72: 95% confidence interval (CI) = 0.69, 0.75 in the fully adjusted model], and the lower risk was evident even for those providing 50 or more h of caregiving per week (adjusted HR = 0.77: 95% CI = 0.71, 0.83 and 0.76: 95% CI = 0.69, 0.83 for men and women, respectively). There was no evidence that this relationship varied by either age or marital status. Even among people with chronic health problems such as poor mental health, caregivers had lower mortality risk than non caregivers. Caregiving is associated with reduced mortality risk for most causes for example, the risk of death from ischaemic heart disease for caregivers providing 50 or more h was 27% and 31% lower for men and for women, respectively, compared with non-caregivers (HR = 0.73: 95% CI = 0.60, 0.88 and HR = 0.69: 95% CI = 0.51, 0.92). CONCLUSIONS: This large population-based study confirms that for the majority of caregivers the beneficial effects of caregiving in terms of short-term mortality risk appear to outweigh any negative effects, even among people with significant health problems. These results underscore the need for a reappraisal of how caregiving is perceived. PMID- 26371208 TI - Commentary: Antidepressants and diabetes risk: why are there discrepant findings from cohort studies based on patient records and those based on serial phenotyping? PMID- 26371209 TI - Reconciling depressed Ca2+ sparks occurrence with enhanced RyR2 activity in failing mice cardiomyocytes. AB - Abnormalities in cardiomyocyte Ca2+ handling contribute to impaired contractile function in heart failure (HF). Experiments on single ryanodine receptors (RyRs) incorporated into lipid bilayers have indicated that RyRs from failing hearts are more active than those from healthy hearts. Here, we analyzed spontaneous Ca2+ sparks (brief, localized increased in [Ca2+]i) to evaluate RyR cluster activity in situ in a mouse post-myocardial infarction (PMI) model of HF. The cardiac ejection fraction of PMI mice was reduced to ~30% of that of sham-operated (sham) mice, and their cardiomyocytes were hypertrophied. The [Ca2+]i transient amplitude and sarcoplasmic reticulum (SR) Ca2+ load were decreased in intact PMI cardiomyocytes compared with those from sham mice, and spontaneous Ca2+ sparks were less frequent, whereas the fractional release and the frequency of Ca2+ waves were both increased, suggesting higher RyR activity. In permeabilized cardiomyocytes, in which the internal solution can be controlled, Ca2+ sparks were more frequent in PMI cells (under conditions of similar SR Ca2+ load), confirming the enhanced RyR activity. However, in intact cells from PMI mice, the Ca2+ sparks frequency normalized by the SR Ca2+ load in that cell were reduced compared with those in sham mice, indicating that the cytosolic environment in intact cells contributes to the decrease in Ca2+ spark frequency. Indeed, using an internal "failing solution" with less ATP (as found in HF), we observed a dramatic decrease in Ca2+ spark frequency in permeabilized PMI and sham myocytes. In conclusion, our data show that, even if isolated RyR channels show more activity in HF, concomitant alterations in intracellular media composition and SR Ca2+ load may mask these effects at the Ca2+ spark level in intact cells. Nonetheless, in this scenario, the probability of arrhythmogenic Ca2+ waves is enhanced, and they play a potential role in the increase in arrhythmia events in HF patients. PMID- 26371211 TI - Stroke: cardiac causes and their management. PMID- 26371212 TI - In Memorium: Guido Tarone 1951-2015. Tributes to Professor Guido Tarone, chairperson, European Society of Cardiology working group onmyocardial function 2014-2016. PMID- 26371210 TI - Na,K-ATPase alpha2 activity in mammalian skeletal muscle T-tubules is acutely stimulated by extracellular K+. AB - The Na,K-ATPase alpha2 isoform is the predominant Na,K-ATPase in adult skeletal muscle and the sole Na,K-ATPase in the transverse tubules (T-tubules). In quiescent muscles, the alpha2 isozyme operates substantially below its maximal transport capacity. Unlike the alpha1 isoform, the alpha2 isoform is not required for maintaining resting ion gradients or the resting membrane potential, canonical roles of the Na,K-ATPase in most other cells. However, alpha2 activity is stimulated immediately upon the start of contraction and, in working muscles, its contribution is crucial to maintaining excitation and resisting fatigue. Here, we show that alpha2 activity is determined in part by the K+ concentration in the T-tubules, through its K+ substrate affinity. Apparent K+ affinity was determined from measurements of the K1/2 for K+ activation of pump current in intact, voltage-clamped mouse flexor digitorum brevis muscle fibers. Pump current generated by the alpha2 Na,K-ATPase, Ip, was identified as the outward current activated by K+ and inhibited by micromolar ouabain. Ip was outward at all potentials studied (-90 to -30 mV) and increased with depolarization in the subthreshold range, -90 to -50 mV. The Q10 was 2.1 over the range of 22-37 degrees C. The K1/2,K of Ip was 4.3+/-0.3 mM at -90 mV and was relatively voltage independent. This K+ affinity is lower than that reported for other cell types but closely matches the dynamic range of extracellular K+ concentrations in the T tubules. During muscle contraction, T-tubule luminal K+ increases in proportion to the frequency and duration of action potential firing. This K1/2,K predicts a low fractional occupancy of K+ substrate sites at the resting extracellular K+ concentration, with occupancy increasing in proportion to the frequency of membrane excitation. The stimulation of preexisting pumps by greater K+ site occupancy thus provides a rapid mechanism for increasing alpha2 activity in working muscles. PMID- 26371213 TI - Effective interventions and strategies for improving early child development. PMID- 26371214 TI - Realising the health and wellbeing of adolescents. PMID- 26371215 TI - Women's health priorities and interventions. PMID- 26371216 TI - Improving the resilience and workforce of health systems for women's, children's, and adolescents' health. PMID- 26371217 TI - Innovating for women's, children's, and adolescents' health. PMID- 26371218 TI - Nutrition and health in women, children, and adolescent girls. PMID- 26371219 TI - Human rights in the new Global Strategy. PMID- 26371220 TI - Ensuring multisectoral action on the determinants of reproductive, maternal, newborn, child, and adolescent health in the post-2015 era. PMID- 26371221 TI - Accountability in the 2015 Global Strategy for Women's, Children's and Adolescents' Health. PMID- 26371223 TI - Financing women's, children's, and adolescents' health. PMID- 26371222 TI - Ending preventable maternal and newborn mortality and stillbirths. PMID- 26371224 TI - National leadership: driving forward the updated Global Strategy for Women's, Children's and Adolescents' Health. PMID- 26371225 TI - Children's health priorities and interventions. PMID- 26371226 TI - Prioritising women's, children's, and adolescents' health in the post-2015 world. PMID- 26371227 TI - Women's, children's, and adolescents' health in humanitarian and other crises. PMID- 26371228 TI - Towards a new Global Strategy for Women's, Children's and Adolescents' Health. PMID- 26371229 TI - California's assembly passes physician assisted dying bill. PMID- 26371230 TI - Pedaling rate is an important determinant of human oxygen uptake during exercise on the cycle ergometer. AB - Estimation of human oxygen uptake (Vo2) during exercise is often used as an alternative when its direct measurement is not feasible. The American College of Sports Medicine (ACSM) suggests estimating human Vo2 during exercise on a cycle ergometer through an equation that considers individual's body mass and external work rate, but not pedaling rate (PR). We hypothesized that including PR in the ACSM equation would improve its Vo2 prediction accuracy. Ten healthy male participants' (age 19-48 years) were recruited and their steady-state Vo2 was recorded on a cycle ergometer for 16 combinations of external work rates (0, 50, 100, and 150 W) and PR (50, 70, 90, and 110 revolutions per minute). Vo2 was calculated by means of a new equation, and by the ACSM equation for comparison. Kinematic data were collected by means of an infrared 3-D motion analysis system in order to explore the mechanical determinants of Vo2. Including PR in the ACSM equation improved the accuracy for prediction of sub-maximal Vo2 during exercise (mean bias 1.9 vs. 3.3 mL O2 kg(-1) min(-1)) but it did not affect the accuracy for prediction of maximal Vo2 (P > 0.05). Confirming the validity of this new equation, the results were replicated for data reported in the literature in 51 participants. We conclude that PR is an important determinant of human Vo2 during cycling exercise, and it should be considered when predicting oxygen consumption. PMID- 26371231 TI - The effects of buthionine sulfoximine treatment on diaphragm contractility and SERCA pump function in adult and middle aged rats. AB - This study examined the effects of 10 days of buthionine sulfoximine (BSO) treatment on in vitro contractility and sarcoplasmic reticulum calcium pump (SERCA) expression and function in adult (AD; 6-8 months old) and middle aged (MA; 14-17 months old) rat diaphragm in both the basal state and following fatiguing stimulation. BSO treatment reduced the cellular concentrations of free glutathione (GSH) by >95% and oxidized glutathione (GSSG) by >80% in both age cohorts. GSH content in AD Control diaphragm was 32% higher (P < 0.01) than in MA Control, with no differences in GSSG. The ratio of GSH:GSSG, an indicator of cellular oxidative state, was 34.6 +/- 7.4 in MA Control, 52.5 +/- 10.1 in AD Control, 10.6 +/- 1.7 in MA BSO, and 9.5 +/- 1.1 in AD BSO (BSO vs. Control, P < 0.05). Several findings suggest that the effects of BSO treatment are age dependent. AD BSO diaphragm had 26% higher twitch and 28% higher tetanic force (both P < 0.05) than AD Controls, whereas no significant difference existed between the two MA groups. In contrast to our previous work on BSO-treated AD rats, BSO treatment did not influence maximal SERCA ATPase activity in MA rat diaphragm, nor did SERCA2a expression increase in BSO-treated MA diaphragm. Biotinylated iodoacetamide binding to SERCA1a, a specific marker of free cysteine residues, was reduced by 35% (P < 0.05) in AD Control diaphragm following fatiguing stimulation, but was not reduced in any other group. Collectively, these results suggest an important role for redox regulation in both contractility and SERCA function which is influenced by aging. PMID- 26371232 TI - Increased maternal nighttime cortisol concentrations in late gestation alter glucose and insulin in the neonatal lamb. AB - Previous studies in our laboratory have shown that a modest chronic increase in maternal cortisol concentrations impairs maternal glucose metabolism and increases the incidence of perinatal stillbirth. The dramatic outcomes prevented our ability to study the effects of maternal hypercortisolemia on neonatal growth, glucose metabolism, and hypothalamo-pituitary-adrenal axis response. Therefore, we developed a model in which pregnant ewes are infused for 12 h/day at 0.5 mg.kg(-1).day(-1) from day 115 of gestation until delivery (~145), elevating nighttime plasma cortisol concentrations. This pattern of elevation of cortisol mimics that in patients with elevated evening cortisol concentrations, as in Cushing's syndrome or chronic depression. Plasma cortisol, glucose, insulin, and electrolytes were measured during pregnancy and postpartum in control and cortisol-infused ewes and their postnatal lambs for the first 14 days after delivery. Neonatal growth and plasma ACTH, aldosterone, renin activity, and electrolytes, and organ weights at 14 days of age were also measured. Infusion of cortisol increased maternal plasma cortisol during pregnancy but not postpartum, and did not alter neonatal ACTH or cortisol. Although maternal glucose and insulin concentrations were not changed by the maternal infusion of cortisol, neonatal plasma glucose was increased and plasma insulin was decreased compared to those in the control group. Neonatal ponderal index and kidney weight were reduced, left ventricular wall thickness was increased, and plasma sodium and creatinine were increased after maternal cortisol infusion. These results suggest that excess maternal cortisol concentrations in late gestation alter growth, glucose and insulin regulation, and organ maturation in the neonate. PMID- 26371233 TI - The Nitrate-Inducible NAC Transcription Factor TaNAC2-5A Controls Nitrate Response and Increases Wheat Yield. AB - Nitrate is a major nitrogen resource for cereal crops; thus, understanding nitrate signaling in cereal crops is valuable for engineering crops with improved nitrogen use efficiency. Although several regulators have been identified in nitrate sensing and signaling in Arabidopsis (Arabidopsis thaliana), the equivalent information in cereals is missing. Here, we isolated a nitrate inducible and cereal-specific NAM, ATAF, and CUC (NAC) transcription factor, TaNAC2-5A, from wheat (Triticum aestivum). A chromatin immunoprecipitation assay showed that TaNAC2-5A could directly bind to the promoter regions of the genes encoding nitrate transporter and glutamine synthetase. Overexpression of TaNAC2 5A in wheat enhanced root growth and nitrate influx rate and, hence, increased the root's ability to acquire nitrogen. Furthermore, we found that TaNAC2-5A overexpressing transgenic wheat lines had higher grain yield and higher nitrogen accumulation in aerial parts and allocated more nitrogen in grains in a field experiment. These results suggest that TaNAC2-5A is involved in nitrate signaling and show that it is an exciting gene resource for breeding crops with more efficient use of fertilizer. PMID- 26371234 TI - Integrative Approaches to Enhance Understanding of Plant Metabolic Pathway Structure and Regulation. AB - Huge insight into molecular mechanisms and biological network coordination have been achieved following the application of various profiling technologies. Our knowledge of how the different molecular entities of the cell interact with one another suggests that, nevertheless, integration of data from different techniques could drive a more comprehensive understanding of the data emanating from different techniques. Here, we provide an overview of how such data integration is being used to aid the understanding of metabolic pathway structure and regulation. We choose to focus on the pairwise integration of large-scale metabolite data with that of the transcriptomic, proteomics, whole-genome sequence, growth- and yield-associated phenotypes, and archival functional genomic data sets. In doing so, we attempt to provide an update on approaches that integrate data obtained at different levels to reach a better understanding of either single gene function or metabolic pathway structure and regulation within the context of a broader biological process. PMID- 26371235 TI - The Arabidopsis Chloroplast Stromal N-Terminome: Complexities of Amino-Terminal Protein Maturation and Stability. AB - Protein amino (N) termini are prone to modifications and are major determinants of protein stability in bacteria, eukaryotes, and perhaps also in chloroplasts. Most chloroplast proteins undergo N-terminal maturation, but this is poorly understood due to insufficient experimental information. Consequently, N termini of mature chloroplast proteins cannot be accurately predicted. This motivated an extensive characterization of chloroplast protein N termini in Arabidopsis (Arabidopsis thaliana) using terminal amine isotopic labeling of substrates and mass spectrometry, generating nearly 14,000 tandem mass spectrometry spectra matching to protein N termini. Many nucleus-encoded plastid proteins accumulated with two or three different N termini; we evaluated the significance of these different proteoforms. Alanine, valine, threonine (often in N-alpha-acetylated form), and serine were by far the most observed N-terminal residues, even after normalization for their frequency in the plastid proteome, while other residues were absent or highly underrepresented. Plastid-encoded proteins showed a comparable distribution of N-terminal residues, but with a higher frequency of methionine. Infrequent residues (e.g. isoleucine, arginine, cysteine, proline, aspartate, and glutamate) were observed for several abundant proteins (e.g. heat shock proteins 70 and 90, Rubisco large subunit, and ferredoxin-glutamate synthase), likely reflecting functional regulation through their N termini. In contrast, the thylakoid lumenal proteome showed a wide diversity of N-terminal residues, including those typically associated with instability (aspartate, glutamate, leucine, and phenylalanine). We propose that, after cleavage of the chloroplast transit peptide by stromal processing peptidase, additional processing by unidentified peptidases occurs to avoid unstable or otherwise unfavorable N-terminal residues. The possibility of a chloroplast N-end rule is discussed. PMID- 26371238 TI - Cardiac Perforation Caused by Cement Embolus After Total Hip Replacement. PMID- 26371236 TI - Drug Therapy for Heart Valve Diseases. PMID- 26371239 TI - Left Main Dissection and Pseudoaneurysm Formation After a Road Traffic Accident. PMID- 26371240 TI - Letter by Sanchis-Gomar et al Regarding Article, "Cardiac Remodeling in Response to 1 Year of Intensive Endurance Training". PMID- 26371241 TI - Letter by Wu et al Regarding Article, "Hydrogen Inhalation During Normoxic Resuscitation Improves Neurological Outcome in a Rat Model of Cardiac Arrest Independently of Targeted Temperature Management". PMID- 26371242 TI - Response to Letter Regarding Article, "Hydrogen Inhalation During Normoxic Resuscitation Improves Neurological Outcome in a Rat Model of Cardiac Arrest Independently of Targeted Temperature Management". PMID- 26371243 TI - The BLT1 Inhibitory Function of alpha-1 Antitrypsin Augmentation Therapy Disrupts Leukotriene B4 Neutrophil Signaling. AB - Leukotriene B4 (LTB4) contributes to many inflammatory diseases, including genetic and nongenetic forms of chronic obstructive pulmonary disease. alpha-1 Antitrypsin (AAT) deficiency (AATD) is characterized by destruction of lung parenchyma and development of emphysema, caused by low AAT levels and a high neutrophil burden in the airways of affected individuals. In this study we assessed whether AATD is an LTB4-related disease and investigated the ability of serum AAT to control LTB4 signaling in neutrophils. In vitro studies demonstrate that neutrophil elastase is a key player in the LTB4 inflammatory cycle in AATD, causing increased LTB4 production, and associated BLT1 membrane receptor expression. AATD patients homozygous for the Z allele were characterized by increased neutrophil adhesion and degranulation responses to LTB4. We demonstrate that AAT can bind LTB4 and that AAT/LTB4 complex formation modulates BLT1 engagement and downstream signaling events, including 1,4,5-triphosphate production and Ca(2+) flux. Additionally, treatment of ZZ-AATD individuals with AAT augmentation therapy decreased plasma LTB4 concentrations and reduced levels of membrane-bound neutrophil elastase. Collectively, these results provide a mechanism by which AAT augmentation therapy impacts on LTB4 signaling in vivo, and not only reinforces the utility of this therapy for resolving inflammation in AATD, but supports useful future clinical applications in treatment of other LTB4 related diseases. PMID- 26371244 TI - Composition, Development, and Function of Uterine Innate Lymphoid Cells. AB - Innate lymphoid cells (ILCs), including NK cells, contribute to barrier immunity and tissue homeostasis. In addition to the role of uterine NK cells in placentation and fetal growth, other uterine ILCs (uILCs) are likely to play roles in uterine physiology and pathology. In this article, we report on the composition of uILCs in the endometrium during the luteal phase and in the decidua during early pregnancy. Whereas nonkiller uILC1s and uILC2s are barely detectable in mouse and not detected in humans, a sizeable population of uILC3s is found in human endometrium and decidua, which are mostly NCR(+) and partially overlap with previously described IL-22-producing uterine NK cells. Development of mouse uILC3 is Nfil3 independent, suggesting unique features of uILCs. Indeed, although the cytokine production profile of mouse uILCs recapitulates that described in other tissues, IL-5, IL-17, and IL-22 are constitutively produced by uILC2s and uILC3s. This study lays the foundation to understand how ILCs function in the specialized uterine mucosa, both in tissue homeostasis and barrier immunity and during pregnancy. PMID- 26371246 TI - The Levels of the Lectin Pathway Serine Protease MASP-1 and Its Complex Formation with C1 Inhibitor Are Linked to the Severity of Hereditary Angioedema. AB - C1 inhibitor (C1-INH) is known to form complexes with the lectin complement pathway serine proteases MASP-1 and MASP-2. Deficiency of C1-INH is associated with hereditary angioedema (HAE), an autosomal inherited disease characterized by swelling attacks caused by elevated levels of bradykinin. MASP-1 was shown to cleave high m.w. kininogen into bradykinin; therefore, we hypothesized that MASP 1 levels and the quantity of MASP-1/C1-INH complexes might be associated with different paraclinical and clinical outcomes of HAE. We measured MASP-1 serum concentrations and endogenous MASP-1/C1-INH complex levels in 128 HAE patients and 100 controls. Relatively high levels of pre-existing MASP-1/C1-INH complexes were observed in normal serum, and we found that both the serum levels of MASP-1 and the complex formation between MASP-1 and C1-INH were significantly reduced in HAE patients compared with matched controls (p < 0.0001). The level of MASP-1 and MASP-1/C1-INH complexes in HE patients correlated with the level of C1-INH (p = 0.0009 and p = 0.0047, respectively), the level of C4 (p = 0.0084 and p < 0.0001, respectively), and the number of attacks in the year of blood sampling (p = 0.0075 and p = 0.0058, respectively). In conclusion, we show that MASP-1/C1-INH complexes circulate in normal human blood. The levels of MASP-1 and MASP-1/C1-INH complexes are reduced in HAE patients compared with controls. Both MASP-1 and MASP-1/C1-INH complexes are related to the degree of complement C4 consumption, as well as the severity of disease. These results suggest that MASP-1 may exert a previously unrecognized role in the pathophysiology of HAE. PMID- 26371245 TI - Annexin A2 Regulates Autophagy in Pseudomonas aeruginosa Infection through the Akt1-mTOR-ULK1/2 Signaling Pathway. AB - Earlier studies reported that a cell membrane protein, Annexin A2 (AnxA2), plays multiple roles in the development, invasion, and metastasis of cancer. Recent studies demonstrated that AnxA2 also functions in immunity against infection, but the underlying mechanism remains largely elusive. Using a mouse infection model, we reveal a crucial role for AnxA2 in host defense against Pseudomonas aeruginosa, as anxa2(-/-) mice manifested severe lung injury, systemic dissemination, and increased mortality compared with wild-type littermates. In addition, anxa2(-/-) mice exhibited elevated inflammatory cytokines (TNF-alpha, IL-6, IL-1beta, and IFN-gamma), decreased bacterial clearance by macrophages, and increased superoxide release in the lung. We further identified an unexpected molecular interaction between AnxA2 and Fam13A, which activated Rho GTPase. P. aeruginosa infection induced autophagosome formation by inhibiting Akt1 and mTOR. Our results indicate that AnxA2 regulates autophagy, thereby contributing to host immunity against bacteria through the Akt1-mTOR-ULK1/2 signaling pathway. PMID- 26371247 TI - Cutaneous Infection with Leishmania major Mediates Heterologous Protection against Visceral Infection with Leishmania infantum. AB - Visceral leishmaniasis (VL) is a fatal disease of the internal organs caused by the eukaryotic parasite Leishmania. Control of VL would best be achieved through vaccination. However, this has proven to be difficult partly because the correlates of protective immunity are not fully understood. In contrast, protective immunity against nonfatal cutaneous leishmaniasis (CL) is well defined and mediated by rapidly recruited, IFN-gamma-producing Ly6C(+)CD4(+) T cells at the dermal challenge site. Protection against CL is best achieved by prior infection or live vaccination with Leishmania major, termed leishmanization. A long-standing question is whether prior CL or leishmanization can protect against VL. Employing an intradermal challenge model in mice, we report that cutaneous infection with Leishmania major provides heterologous protection against visceral infection with Leishmania infantum. Protection was associated with a robust CD4(+) T cell response at the dermal challenge site and in the viscera. In vivo labeling of circulating cells revealed that increased frequencies of IFN gamma(+)CD4(+) T cells at sites of infection are due to recruitment or retention of cells in the tissue, rather than increased numbers of cells trapped in the vasculature. Shortly after challenge, IFN-gamma-producing cells were highly enriched for Ly6C(+)T-bet(+) cells in the viscera. Surprisingly, this heterologous immunity was superior to homologous immunity mediated by prior infection with L. infantum. Our observations demonstrate a common mechanism of protection against different clinical forms of leishmaniasis. The efficacy of leishmanization against VL may warrant the introduction of the practice in VL endemic areas or during outbreaks of disease. PMID- 26371249 TI - Cutting Edge: IL-25 Targets Dendritic Cells To Attract IL-9-Producing T Cells in Acute Allergic Lung Inflammation. AB - Asthma is a common inflammatory disease of airways that is often associated with type 2 responses triggered by allergens, such as house dust mites (HDMs). IL-25 is a key mucosal cytokine that may be produced by stressed epithelial cells; it rapidly activates type 2 innate lymphoid cells to produce IL-13 and IL-5. When administered directly into lungs, IL-25 induces acute inflammation. However, the mechanisms underlying IL-25-initiated inflammation and the roles of this cytokine in the context of HDM-induced allergic inflammation are not fully understood. We show in this article that lung-resident conventional dendritic cells were direct targets of IL-25. IL-25-stimulated dendritic cells rapidly induced mediators, such as the chemokine CCL17, which, in turn, attracted IL-9-producing T cells. Importantly, these mechanisms also operated during HDM-induced allergic lung inflammation. PMID- 26371248 TI - Fibrocytes Regulate Wilms Tumor 1-Positive Cell Accumulation in Severe Fibrotic Lung Disease. AB - Collagen-producing myofibroblast transdifferentiation is considered a crucial determinant in the formation of scar tissue in the lungs of patients with idiopathic pulmonary fibrosis. Multiple resident pulmonary cell types and bone marrow-derived fibrocytes have been implicated as contributors to fibrotic lesions because of the transdifferentiation potential of these cells into myofibroblasts. In this study, we assessed the expression of Wilms tumor 1 (WT1), a known marker of mesothelial cells, in various cell types in normal and fibrotic lungs. We demonstrate that WT1 is expressed by both mesothelial and mesenchymal cells in idiopathic pulmonary fibrosis lungs but has limited or no expression in normal human lungs. We also demonstrate that WT1(+) cells accumulate in fibrotic lung lesions, using two different mouse models of pulmonary fibrosis and WT1 promoter-driven fluorescent reporter mice. Reconstitution of bone marrow cells into a TGF-alpha transgenic mouse model demonstrated that fibrocytes do not transform into WT1(+) mesenchymal cells, but they do augment accumulation of WT1(+) cells in severe fibrotic lung disease. Importantly, the number of WT1(+) cells in fibrotic lesions was correlated with severity of lung disease as assessed by changes in lung function, histology, and hydroxyproline levels in mice. Finally, inhibition of WT1 expression was sufficient to attenuate collagen and other extracellular matrix gene production by mesenchymal cells from both murine and human fibrotic lungs. Thus, the results of this study demonstrate a novel association between fibrocyte-driven WT1(+) cell accumulation and severe fibrotic lung disease. PMID- 26371250 TI - Expression, Function, and Molecular Properties of the Killer Receptor Ncr1-Noe. AB - NK cells kill various cells using activating receptors, such as the natural cytotoxicity receptors (NCRs). NKp46 is a major NCR and is the only NCR expressed in mice (denoted Ncr1). Using Ncr1-deficient mice (Ncr1(gfp/pfp)) we demonstrated that Ncr1 controls various pathologies, and that in its absence Ncr1-related functions are impaired. In 2012, another Ncr1-related mouse was generated, named Noe, in which a random mutation, W32R, in position 32, impaired the Ncr1-Noe cell surface expression. Interestingly, in the Noe mice, Ncr1-dependent deficiencies were not observed. Additionally, the Noe-NK cells were hyperactivated, probably due to increased Helios expression, and the Noe mice demonstrate increased clearance of influenza and murine CMV. In contrast, in the Ncr1(gfp/pfp) mice infection with influenza was lethal and we show in the present study no difference in murine CMV infection between Ncr1(gfp/pfp) and wild-type (WT) mice. Because the foremost difference between the Noe and Ncr1(gfp/gfp) mice is the presence of a mutated Ncr1-Noe protein, we studied its properties. We show that Ncr1-Noe and various other Ncr1 mutants in position 32 can be expressed on the surface, albeit slowly and unstably, and that ligand recognition and function of the various Ncr1-Noe is similar to the WT Ncr1. We further show that the glycosylation pattern of Ncr1-Noe is aberrant, that the Ncr1-Noe proteins accumulate in the endoplasmic reticulum, and that the expression of Ncr1-Noe proteins, but not WT Ncr1, leads to increased Helios expression. Thus, we suggest that the NK hyperactivated phenotype observed in the Noe mice might result from the presence of the Ncr1-Noe protein. PMID- 26371251 TI - Diverse Gene Expression in Human Regulatory T Cell Subsets Uncovers Connection between Regulatory T Cell Genes and Suppressive Function. AB - Regulatory T (Treg) cells have a critical role in the control of immunity, and their diverse subpopulations may allow adaptation to different types of immune responses. In this study, we analyzed human Treg cell subpopulations in the peripheral blood by performing genome-wide expression profiling of 40 Treg cell subsets from healthy donors. We found that the human peripheral blood Treg cell population is comprised of five major genomic subgroups, represented by 16 tractable subsets with a particular cell surface phenotype. These subsets possess a range of suppressive function and cytokine secretion and can exert a genomic footprint on target effector T (Teff) cells. Correlation analysis of variability in gene expression in the subsets identified several cell surface molecules associated with Treg suppressive function, and pharmacological interrogation revealed a set of genes having causative effect. The five genomic subgroups of Treg cells imposed a preserved pattern of gene expression on Teff cells, with a varying degree of genes being suppressed or induced. Notably, there was a cluster of genes induced by Treg cells that bolstered an autoinhibitory effect in Teff cells, and this induction appears to be governed by a different set of genes than ones involved in counteracting Teff activation. Our work shows an example of exploiting the diversity within human Treg cell subpopulations to dissect Treg cell biology. PMID- 26371252 TI - Cutting Edge: Resident Memory CD8 T Cells Express High-Affinity TCRs. AB - Tissue-resident memory T (TRM) cells serve as vanguards of antimicrobial host defense in nonlymphoid tissues, particularly at barrier epithelia and in organs with nonrenewable cell types (e.g., brain). In this study, we asked whether an augmented ability to sense Ag complemented their role as early alarms of pathogen invasion. Using mouse polyomavirus, we show that brain-resident mouse polyomavirus-specific CD8 T cells, unlike memory cells in the spleen, progressively increase binding to MHC class I tetramers and CD8 coreceptor expression. Using the two-dimensional micropipette adhesion-frequency assay, we show that TRM cells in brain, as well as in kidney, express TCRs with up to 20 fold higher affinity than do splenic memory T cells, whereas effector cells express TCRs of similar high affinity in all organs. Together, these data demonstrate that TRM cells retain high TCR affinity, which endows them with the high Ag sensitivity needed for front-line defense against infectious agents. PMID- 26371253 TI - Acute-Phase Deaths from Murine Polymicrobial Sepsis Are Characterized by Innate Immune Suppression Rather Than Exhaustion. AB - Sepsis, a leading cause of death in the United States, has poorly understood mechanisms of mortality. To address this, our model of cecal ligation and puncture (CLP) induced sepsis stratifies mice as predicted to Live (Live-P) or Die (Die-P) based on plasma IL-6. Six hours post-CLP, both Live-P and Die-P groups have equivalent peritoneal bacterial colony forming units and recruitment of phagocytes. By 24 h, however, Die-P mice have increased bacterial burden, despite increased neutrophil recruitment, suggesting Die-P phagocytes have impaired bacterial killing. Peritoneal cells were used to study multiple bactericidal processes: bacterial killing, reactive oxygen species (ROS) generation, and phagocytosis. Total phagocytosis and intraphagosomal processes were determined with triple-labeled Escherichia coli, covalently labeled with ROS and pH-sensitive probes, and an ROS/pH-insensitive probe for normalization. Although similar proportions of Live-P and Die-P phagocytes responded to exogenous stimuli, Die-P phagocytes showed marked deficits in all parameters measured, thus suggesting immunosuppression rather than exhaustion. This contradicts the prevailing sepsis paradigm that acute-phase sepsis deaths (<5 d) result from excessive inflammation, whereas chronic-phase deaths (>5 d) are characterized by insufficient inflammation and immunosuppression. These data suggest that suppression of cellular innate immunity in sepsis occurs within the first 6 h. PMID- 26371254 TI - RP105 Engages Phosphatidylinositol 3-Kinase p110delta To Facilitate the Trafficking and Secretion of Cytokines in Macrophages during Mycobacterial Infection. AB - Cytokines are key regulators of adequate immune responses to infection with Mycobacterium tuberculosis. We demonstrate that the p110delta catalytic subunit of PI3K acts as a downstream effector of the TLR family member RP105 (CD180) in promoting mycobacteria-induced cytokine production by macrophages. Our data show that the significantly reduced release of TNF and IL-6 by RP105(-/-) macrophages during mycobacterial infection was not accompanied by diminished mRNA or protein expression. Mycobacteria induced comparable activation of NF-kappaB and p38 MAPK signaling in wild-type (WT) and RP105(-/-) macrophages. In contrast, mycobacteria induced phosphorylation of Akt was abrogated in RP105(-/-) macrophages. The p110delta-specific inhibitor, Cal-101, and small interfering RNA-mediated knockdown of p110delta diminished mycobacteria-induced TNF secretion by WT but not RP105(-/-) macrophages. Such interference with p110delta activity led to reduced surface-expressed TNF in WT but not RP105(-/-) macrophages, while leaving TNF mRNA and protein expression unaffected. Activity of Bruton's tyrosine kinase was required for RP105-mediated activation of Akt phosphorylation and TNF release by mycobacteria-infected macrophages. These data unveil a novel innate immune signaling axis that orchestrates key cytokine responses of macrophages and provide molecular insight into the functions of RP105 as an innate immune receptor for mycobacteria. PMID- 26371255 TI - Cyprinid Herpesvirus 3 Il10 Inhibits Inflammatory Activities of Carp Macrophages and Promotes Proliferation of Igm+ B Cells and Memory T Cells in a Manner Similar to Carp Il10. AB - Cyprinid herpesvirus 3 (CyHV-3) is the causative agent of a lethal disease of carp and encodes for an Il10 homolog (ORF134). Our previous studies with a recombinant ORF134-deleted strain and the derived revertant strain suggested that cyprinid herpesvirus 3 Il10 (CyHV-3 Il10 [cyhv3Il10]) is not essential for viral replication in vitro, or virulence in vivo. In apparent contrast, cyhv3Il10 is one of the most abundant proteins of the CyHV-3 secretome and is structurally very similar to carp Il10 and also human IL10. To date, studies addressing the biological activity of cyhv3Il10 on cells of its natural host have not been performed. To address the apparent contradiction between the presence of a structurally conserved Il10 homolog in the genome of CyHV-3 and the lack of a clear phenotype in vivo using recombinant cyhv3Il10-deleted viruses, we used an in vitro approach to investigate in detail whether cyhv3Il10 exerts any biological activity on carp cells. In this study, we provide direct evidence that cyhv3Il10 is biologically active and, similarly to carp Il10, signals via a conserved Stat3 pathway modulating immune cells of its natural host, carp. In vitro, cyhv3Il10 deactivates phagocytes with a prominent effect on macrophages, while also promoting proliferation of Igm(+) B cells and memory T cells. Collectively, this study demonstrates a clear biological activity of cyhv3Il10 on cells of its natural host and indicates that cyhv3Il10 is a true viral ortholog of carp Il10. Furthermore, to our knowledge, this is the first report on biological activities of a nonmammalian viral Il10 homolog. PMID- 26371257 TI - Identification of Thiostrepton as a Novel Inhibitor for Psoriasis-like Inflammation Induced by TLR7-9. AB - Activation of TLR7-9 has been linked to the pathogenesis of autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, and psoriasis. Thus, therapeutic applications of antagonists of these TLRs for such disorders are being investigated. Bortezomib (Velcade) is a proteasome inhibitor known to suppress activation of these TLRs. To identify novel TLR7-9 inhibitors, we searched the Gene Expression Omnibus database for gene expression profiles of bortezomib-treated cells. These profiles were then used to screen the Connectivity Map database for chemical compounds with similar functions as bortezomib. A natural antibiotic, thiostrepton, was identified for study. Similar to bortezomib, thiostrepton effectively inhibits TLR7-9 activation in cell-based assays and in dendritic cells. In contrast to bortezomib, thiostrepton does not inhibit NF-kappaB activation induced by TNF-alpha, IL-1, and other TLRs, and it is less cytotoxic to dendritic cells. Thiostrepton inhibits TLR9 localization in endosomes for activation via two mechanisms, which distinguish it from currently used TLR7-9 inhibitors. One mechanism is similar to the proteasome inhibitory function of bortezomib, whereas the other is through inhibition of endosomal acidification. Accordingly, in different animal models, thiostrepton attenuated LL37- and imiquimod-induced psoriasis-like inflammation. These results indicated that thiostrepton is a novel TLR7-9 inhibitor, and compared with bortezomib, its inhibitory effect is more specific to these TLRs, suggesting the potential therapeutic applications of thiostrepton on immunologic disorders elicited by inappropriate activation of TLR7-9. PMID- 26371258 TI - Voluntary stopping of eating and drinking (VSED), physician-assisted death (PAD), or neither in the last stage of life? Both should be available as a last resort. PMID- 26371259 TI - Voluntary stopping of eating and drinking (VSED), physician-assisted suicide (PAS), or neither in the last stage of life? PAS: no; VSED: it depends. PMID- 26371256 TI - A Distinctive Cytoplasmic Tail Contributes to Low Surface Expression and Intracellular Retention of the Patr-AL MHC Class I Molecule. AB - Chimpanzees have orthologs of the six fixed, functional human MHC class I genes. But, in addition, the chimpanzee has a seventh functional gene, Patr-AL, which is not polymorphic but contributes substantially to population diversity by its presence on only 50% of MHC haplotypes. The ancestral AL gene emerged long before the separation of human and chimpanzee ancestors and then subsequently and specifically lost function during human evolution, but was maintained in chimpanzees. Patr-AL is an alloantigen that participates in negative and positive selection of the T cell repertoire. The three-dimensional structure and the peptide-binding repertoire of Patr-AL and HLA-A*02 are surprisingly similar. In contrast, the expression of these two molecules is very different, as shown using specific mAbs and polyclonal Abs made against Patr-AL. Peripheral blood cells and B cell lines express low levels of Patr-AL at the cell surface. Higher levels are seen for 221-cell transfectants expressing Patr-AL, but in these cells a large majority of Patr-AL molecules are retained in the early compartments of the secretory pathway: mainly the endoplasmic reticulum, but also cis-Golgi. Replacing the cytoplasmic tail of Patr-AL with that of HLA-A*02 increased the cell-surface expression of Patr-AL substantially. Four substitutions distinguish the Patr-AL and HLA-A*02 cytoplasmic tails. Systematic mutagenesis showed that each substitution contributes changes in cell-surface expression. The combination of residues present in Patr-AL appears unique, but each individual residue is present in other primate MHC class I molecules, notably MHC-E, the most ancient of the functional human MHC class I molecules. PMID- 26371260 TI - Correction to Ryan AM, Shortel SM, Ramsay PP, Casalino LP. Ann Fam Med. 2015;13(4)321-324. PMID- 26371261 TI - A stepped-wedge evaluation of an initiative to spread the collaborative care model for depression in primary care. AB - PURPOSE: Scale-up and spread of evidence-based practices is one of the most important challenges facing health care. We tested whether a statewide initiative, Depression Improvement Across Minnesota-Offering a New Direction (DIAMOND), to implement the collaborative care model for depression in 75 primary care clinics resulted in patient outcome improvements corresponding to those reported in randomized controlled trials. METHODS: Health plans provided a new monthly payment to participating clinics after a 6-month intensive training program with ongoing data submission, networking, and consultation. Implementation was staggered, with 5 sequences of 10 to 40 clinics every 6 months. Payers provided weekly contact information for members from participating clinics who were filling antidepressant prescriptions, and we conducted baseline and 6-month surveys of 1,578 patients about their care and outcomes. RESULTS: There were 466 patients in DIAMOND clinics who received usual care before implementation (UCB), 559 who received usual care in DIAMOND clinics after implementation (UCA), 245 who received DIAMOND care after implementation (DCA), and 308 who received usual care in comparison clinics (UC). Patients who received DIAMOND care after implementation reported more collaborative care depression services than the 3 comparison groups (10.9 vs 6.4-6.7, on a scale of 0 of 14, where higher numbers indicate more services; P <.001) and more satisfaction with their care (4.0 vs 3.4 on a scale 1 to 5, in which higher scores indicate higher satisfaction; P <=.001). Depression remission rates, however, were not significantly different among the 4 groups (36.4% DCA vs 35.8% UCB, 35.0% UCA, 33.9% UC; P = .94). CONCLUSIONS: Despite the incentive of a supporting payment change and intensive training and support for clinics volunteering to participate, no difference in depression outcomes was documented. Specific unmeasured actions present in trials but not present in these clinics may be critical for successful outcome improvement. PMID- 26371262 TI - Primary care patients hastening death by voluntarily stopping eating and drinking. AB - PURPOSE: Little is known about the role family physicians play when a patient deliberately hastens death by voluntarily stopping eating and drinking (VSED). The purpose of this study was to gain more insight for family physicians when confronted with patients who wish to hasten death by VSED. We aimed to describe physicians' involvement in VSED, to describe characteristics and motives of their patients, and to describe the process of VSED in terms of duration, as well as common symptoms in the last 3 days of life. METHODS: We undertook a survey of a random national sample of 1,100 family physicians (response rate 72%), and 500 of these physicians received questions about their last patient who hastened death by VSED. RESULTS: Of the 978 eligible physicians, 708 responded (72.4%); 46% had cared for a patient who hastened death by VSED. Of the 500 physicians who received the additional questions, 440 were eligible and 285 (64.8%) responded; they described 99 cases of VSED. Seventy percent of these patients were aged older than 80 years, 76% had severe disease (27% with cancer), and 77% were dependent on others for everyday care. Frequent reasons for the patients' death wish were somatic (79%), existential (77%), and dependence (58%). Median time until death was 7 days, and the most common symptoms before death were pain, fatigue, impaired cognitive functioning, and thirst or dry throat. Family physicians were involved in 62% of cases. CONCLUSIONS: Patients who hasten death by VSED are mostly in poor health. It is not unlikely for family physicians to be confronted with VSED. They can play an important role in caring for these patients and their proxies by informing them of VSED and by providing support and symptom management during VSED. PMID- 26371263 TI - The cost of sustaining a patient-centered medical home: experience from 2 states. AB - PURPOSE: As medical practices transform to patient-centered medical homes (PCMHs), it is important to identify the ongoing costs of maintaining these "advanced primary care" functions. A key required input is personnel effort. This study's objective was to assess direct personnel costs to practices associated with the staffing necessary to deliver PCMH functions as outlined in the National Committee for Quality Assurance Standards. METHODS: We developed a PCMH cost dimensions tool to assess costs associated with activities uniquely required to maintain PCMH functions. We interviewed practice managers, nurse supervisors, and medical directors in 20 varied primary care practices in 2 states, guided by the tool. Outcome measures included categories of staff used to perform various PCMH functions, time and personnel costs, and whether practices were delivering PCMH functions. RESULTS: Costs per full-time equivalent primary care clinician associated with PCMH functions varied across practices with an average of $7,691 per month in Utah practices and $9,658 in Colorado practices. PCMH incremental costs per encounter were $32.71 in Utah and $36.68 in Colorado. The average estimated cost per member per month for an assumed panel of 2,000 patients was $3.85 in Utah and $4.83 in Colorado. CONCLUSIONS: Identifying costs of maintaining PCMH functions will contribute to effective payment reform and to sustainability of transformation. Maintenance and ongoing support of PCMH functions require additional time and new skills, which may be provided by existing staff, additional staff, or both. Adequate compensation for ongoing and substantial incremental costs is critical for practices to sustain PCMH functions. PMID- 26371264 TI - A population-based study evaluating family physicians' HIV experience and care of people living with HIV in Ontario. AB - PURPOSE: Greater physician experience managing human immunodeficiency virus (HIV) infection has been associated with better HIV-specific outcomes. The objective of this study was to evaluate whether the HIV experience of a family physician modifies the association between the model of care delivery and the quality of care for people living with HIV. METHODS: We retrospectively analyzed data from a population-based observational study conducted between April 1, 2009, and March 31, 2012. A total of 13,417 patients with HIV in Ontario were stratified into 5 possible patterns or models of care. We used multivariable hierarchical logistic regression analyses, adjusted for patient characteristics and pairwise comparisons, to evaluate the modification of the association between care model and indicators of quality of care (receipt of antiretroviral therapy, cancer screening, and health care use) by level of physician HIV experience (<=5, 6-49, >=50 patients during study period). RESULTS: The majority of HIV-positive patients (52.8%) saw family physicians exclusively for their care. Among these patients, receipt of antiretroviral therapy was significantly lower for those receiving care from family physicians with 5 or fewer patients and 6-49 patients compared with those with 50 or more patients (mean levels of adherence [95% CIs] were 0.34 [0.30-0.39] and 0.40 [0.34-0.45], respectively, vs 0.77 [0.74-0.80]). Patients' receipt of cancer screenings and health care use were unrelated to family physician HIV experience. CONCLUSIONS: Family physician HIV experience was strongly associated with receipt of antiretroviral therapy by HIV-positive patients, especially among those seeing only family physicians for their care. Future work must determine the best models for integrating and delivering comprehensive HIV care among diverse populations and settings. PMID- 26371266 TI - Primary care physician insights into a typology of the complex patient in primary care. AB - PURPOSE: Primary care physicians play unique roles caring for complex patients, often acting as the hub for their care and coordinating care among specialists. To inform the clinical application of new models of care for complex patients, we sought to understand how these physicians conceptualize patient complexity and to develop a corresponding typology. METHODS: We conducted qualitative in-depth interviews with internal medicine primary care physicians from 5 clinics associated with a university hospital and a community health hospital. We used systematic nonprobabilistic sampling to achieve an even distribution of sex, years in practice, and type of practice. The interviews were analyzed using a team-based participatory general inductive approach. RESULTS: The 15 physicians in this study endorsed a multidimensional concept of patient complexity. The physicians perceived patients to be complex if they had an exacerbating factor-a medical illness, mental illness, socioeconomic challenge, or behavior or trait (or some combination thereof)-that complicated care for chronic medical illnesses. CONCLUSION: This perspective of primary care physicians caring for complex patients can help refine models of complexity to design interventions or models of care that improve outcomes for these patients. PMID- 26371265 TI - Prevalence, correlates, and outcomes of multimorbidity among patients attending primary care in Odisha, India. AB - PURPOSE: Little information is available on multimorbidity in primary care in India. Because primary care is the first contact of health care for most of the population and important for coordinating chronic care, we wanted to examine the prevalence and correlates of multimorbidity in India and its association with health care utilization. METHODS: Using a structured multimorbidity assessment protocol, we conducted a cross-sectional study, collecting information on 22 self reported chronic conditions in a representative sample of 1,649 adult primary care patients in Odisha, India. RESULTS: The overall age- and sex-adjusted prevalence of multimorbidity was 28.3% (95% CI, 24.3-28.6) ranging from 5.8% in patients aged 18 to 29 years to 45% in those aged older than 70 years. Older age, female sex, higher education, and high income were associated with significantly higher odds of multimorbidity. After adjusting for age, sex, socioeconomic status (SES), education, and ethnicity, the addition of each chronic condition, as well as consultation at private hospitals, was associated with significant increase in the number of medicines intake per person per day. Increasing age and higher education status significantly raised the number of hospital visits per person per year for patients with multiple chronic conditions. CONCLUSION: Our findings of higher prevalence of multimorbidity and hospitalizations in higher SES individuals contrast with findings in Western countries, where lower SES is associated with a greater morbidity burden. PMID- 26371267 TI - A participatory model of the paradox of primary care. AB - PURPOSE: The paradox of primary care is the observation that primary care is associated with apparently low levels of evidence-based care for individual diseases, but systems based on primary care have healthier populations, use fewer resources, and have less health inequality. The purpose of this article is to explore, from a complex systems perspective, mechanisms that might account for the effects of primary care beyond disease-specific care. METHODS: In an 8 session, participatory group model-building process, patient, caregiver, and primary care clinician community stakeholders worked with academic investigators to develop and refine an agent-based computer simulation model to test hypotheses about mechanisms by which features of primary care could affect health and health equity. RESULTS: In the resulting model, patients are at risk for acute illness, acute life-changing illness, chronic illness, and mental illness. Patients have changeable health behaviors and care-seeking tendencies that relate to their living in advantaged or disadvantaged neighborhoods. There are 2 types of care available to patients: primary and specialty. Primary care in the model is less effective than specialty care in treating single diseases, but it has the ability to treat multiple diseases at once. Primary care also can provide disease prevention visits, help patients improve their health behaviors, refer to specialty care, and develop relationships with patients that cause them to lower their threshold for seeking care. In a model run with primary care features turned off, primary care patients have poorer health. In a model run with all primary care features turned on, their conjoint effect leads to better population health for patients who seek primary care, with the primary care effect being particularly pronounced for patients who are disadvantaged and patients with multiple chronic conditions. Primary care leads to more total health care visits that are due to more disease prevention visits, but there are reduced illness visits among people in disadvantaged neighborhoods. Supplemental appendices provide a working version of the model and worksheets that allow readers to run their own experiments that vary model parameters. CONCLUSION: This simulation model provides insights into possible mechanisms for the paradox of primary care and shows how participatory group model building can be used to evaluate hypotheses about the behavior of such complex systems as primary health care and population health. PMID- 26371268 TI - Managing patients with heart failure: a qualitative study of multidisciplinary teams with specialist heart failure nurses. AB - PURPOSE: The purpose of this study was to explore the perceptions and experiences of health care clinicians working in multidisciplinary teams that include specialist heart failure nurses when caring for the management of heart failure patients. METHODS: We used a qualitative in-depth interview study nested in a broader ethnographic study of unplanned admissions in heart failure patients (HoldFAST). We interviewed 24 clinicians across primary, secondary, and community care in 3 locations in the Midlands, South Central, and South West of England. RESULTS: Within a framework of the role and contribution of the heart failure specialist nurse, our study identified 2 thematic areas that the clinicians agreed still represent particular challenges when working with heart failure patients. The first was communication with patients, in particular explaining the diagnosis and helping patients to understand the condition. The participants recognized that such communication was most effective when they had a long-term relationship with patients and families and that the specialist nurse played an important part in achieving this relationship. The second was communication within the team. Multidisciplinary input was especially needed because of the complexity of many patients and issues around medications, and the participants believed the specialist nurse may facilitate team communication. CONCLUSIONS: The study highlights the role of specialist heart failure nurses in delivering education tailored to patients and facilitating better liaison among all clinicians, particularly when dealing with the management of comorbidities and drug regimens. The way in which specialist nurses were able to be caseworkers for their patients was perceived as a method of ensuring coordination and continuity of care. PMID- 26371269 TI - Learning from no-fault treatment injury claims to improve the safety of older patients. AB - New Zealand's treatment injury compensation claims data set provides an uncommon no-fault perspective of patient safety incidents. Analysis of primary care claims data confirmed medication as the leading threat to the safety of older patients in primary care and drew particular attention to the threat posed by antibiotics. For most injuries there was no suggestion of error. The no-fault perspective reveals the greatest threat to the safety of older patients in primary care to be, not error, but the risk posed by treatment itself. To improve patients' safety, in addition to reducing error, clinicians need to reduce patients' exposure to treatment risk, where appropriate. PMID- 26371271 TI - Cancer risk assessment tools in primary care: a systematic review of randomized controlled trials. AB - PURPOSE: We conducted this review to identify published randomized controlled trials (RCTs) of cancer risk assessment tools used in primary care and to determine their impact on clinical utility (clinicians), screening uptake (patients), and psychosocial outcomes (patients). METHODS: We searched EMBASE, PubMed and the Cochrane databases for RCTs of cancer risk assessment tools in primary care up to May 2014. Only studies set in primary care, with patients eligible for screening, and English-language articles were included. RESULTS: The review included 11 trials of 7 risk tools. The trials were heterogeneous with respect to type of tool that was used, type(s) of cancer assessed, and outcomes measured. Evidence suggested risk tools improved patient risk perception, knowledge, and screening intentions, but not necessarily screening behavior. Overall, uptake of a tool was greater if initiated by patients, if used by a dedicated clinician, and when combined with decision support. There was no increase in cancer worry. Health promotion messages within the tool had positive effects on behavior change. Trials were limited by low-recruitment uptake, and the heterogeneity of the findings necessitated a narrative review rather than a meta-analysis. CONCLUSIONS: Risk tools may increase intentions to have cancer screening, but additional interventions at the clinician or health system levels may be needed to increase risk-appropriate cancer screening behavior. PMID- 26371272 TI - I'm a doctor. Can I help? AB - Medical school does not prepare trainees for the reality of the practice of medicine, where book knowledge takes second place to the more pragmatic skills of time management, conflict resolution, and damage control. Junior residents, overwhelmed by the demands of daily floor work, can easily lose sight of the reasons that they went into medicine to begin with. Taken out of the context of the hospital, though, the opportunity to care for a patient one-on-one can be a vital reminder of the gift that is to know how to heal the sick. Reflecting on the opportunity to care for an accident victim at the scene, rather than in the hospital, reinforces to one young physician the remarkable thing that it is to be a physician. PMID- 26371270 TI - Overcoming challenges in the changing environment of practice-based research. AB - PURPOSE: Conducting studies in national practice-based research networks presents logistic and methodologic challenges. Pediatric Research in Office Settings (PROS) has learned valuable lessons in implementing new strategies and adapting to challenges. We describe practical challenges and results of novel applied strategies in implementing and testing the Clinical Effort Against Secondhand Smoke Exposure (CEASE) intervention as part of a national-level cluster randomized controlled trial. METHODS: In the trial, 20 PROS practices were randomized to either a CEASE intervention arm or a control arm. Parents of children seen in the office who indicated smoking in the past 7 days were asked to complete a postvisit enrollment interview and telephone interviews 3 and 12 months later. Identified challenges included (1) recruiting 20 practices serving a high percentage of parent smokers; (2) screening all parents bringing children for visits and enrolling eligible parents who smoked; and (3) achieving an acceptable 12-month telephone response rate. RESULTS: A total of 47 interested practices completed the Practice Population Survey, of which 20 practices in 16 states completed parent enrollment. Thirty-two research assistants screened 18,607 parents and enrolled 1,980 of them. The initial telephone interview response rate was 56% at 12 months, with incorrect and disconnected numbers accounting for nearly 60% of nonresponses. The response rate rose to 67% after practices supplied 532 new contact numbers and 754 text messages were sent, with 389 parents completing interviews. CONCLUSION: The strategies we used to overcome methodologic barriers in conducting a national intervention trial allowed data collection to be completed in the office setting and increased the telephone interview response rate. PMID- 26371275 TI - Influencing student specialty choice: the 4 Pillars for Primary Care Physician Workforce Development. PMID- 26371276 TI - The Residency Performance Index (RPI): an AFMRD tool for family medicine residency program assessment. PMID- 26371277 TI - PBRN Conference highlights stakeholder engagement and dangerous ideas. PMID- 26371278 TI - Direct Primary Care (DPC) Summit draws hundreds of enthusiastic family physicians. PMID- 26371279 TI - Characterization of Hairdresser Exposure to Airborne Particles during Hair Bleaching. AB - Respiratory symptoms among hairdressers are often ascribed to the use of bleaching powders that contain persulfate salts. Such salts can act as allergens and airway irritants but the mechanisms behind the negative health effects are not fully known. In order to understand why some hairdressers experience respiratory symptoms during, and after, sessions of hair bleaching, it is of importance to characterize how exposure occurs. In this work we used time and particle size resolved instrumentation with the aim to measure the concentration of particles that hairdressers are exposed to during sessions of hair bleaching. We also used filter samples to collect particles for quantitative determination of persulfate (S2O8(2-)) content and for analysis by light microscopy. Two different types of bleaching powders were used, one marked as dust-free and one without this marking (denoted regular). The time resolved instrumentation revealed that particles <10 um were emitted, specifically when the regular powder was prepared and mixed with hydrogen peroxide. In contrast to other research our work also revealed that supercoarse particles (>10 um) were emitted during application of the bleaching, when both the regular and the dust-free powders were used. The measured level of persulfate, sampled in the breathing zone of the hairdressers, was on average 26 ug m(-3) when the regular powder was used and 11 ug m(-3) when the dust-free powder was used. This indicates that use of dust-free powder does not eliminate exposure to persulfates, it only lowers the concentration. We show that the site of sampling, or position of the hairdresser with regards to the hair being bleached, is of high importance in the determination of persulfate levels and exposure. This work focuses on the physical and chemical characterization of the particles released to the air and the results are important for accurate exposure assessments. Accurate assessments may in turn lead to a better understanding of why some hairdressers experience respiratory symptoms from hair bleaching sessions. PMID- 26371280 TI - Lis1 restricts the conformational changes in cytoplasmic dynein on microtubules. AB - Cytoplasmic dynein is a microtubule-based motor protein that transports intracellular cargo and performs various functions during cell division. We previously reported that Lis1 suppressed dynein motility on microtubules in an idling state. Recently, a model showed that Lis1 prevents the ATPase domain of dynein from transmitting a detachment signal to its microtubule-binding domain. However, conformational information on dynein is limited. We used electron microscopy to investigate the conformation of dynein and nucleotide-induced conformational changes on microtubules. The conformation of dynein differed depending on the presence or absence of a nucleotide. In the presence of the nucleotide ADP-vanadate, dynein displayed an extended form on microtubules (extended form), whereas in the absence of a nucleotide, dynein lay along microtubules (compact form). This conformational change reflects chemomechanical coupling in dynein walking on microtubules. We also found that Lis1 fixed the conformation of dynein in the compact form regardless of the nucleotide condition. Removal of the Lis1 dimerization motif abolished Lis1-dependent fixation of dynein in the compact form. This suggests that the idling state of dynein on microtubules induced by Lis1 occurs through the Lis1-dependent arrest of dynein chemomechanical coupling. PMID- 26371281 TI - Analysis of improvement in performance and design parameters for enhancing resolution in an atmospheric scanning electron microscope. AB - The scanning electron microscope is used in various fields to go beyond diffraction limits of the optical microscope. However, the electron pathway should be conducted in a vacuum so as not to scatter electrons. The pretreatment of the sample is needed for use in the vacuum. To directly observe large and fully hydrophilic samples without pretreatment, the atmospheric scanning electron microscope (ASEM) is needed. We developed an electron filter unit and an electron detector unit for implementation of the ASEM. The key of the electron filter unit is that electrons are transmitted while air molecules remain untransmitted through the unit. The electron detector unit collected the backscattered electrons. We conducted experiments using the selected materials with Havar foil, carbon film and SiN film. PMID- 26371283 TI - Designs of preoperative biomarkers trials in oncology: a systematic review of the literature. AB - BACKGROUND: The identification of predictive and pharmacodynamics (PD) biomarkers of efficacy of anticancer-targeted therapies is not always straightforward. To address this problem, preoperative trials have been set up. The present study aimed at evaluating how these trials are designed. DESIGN: We retrieved all preoperative oncology trials, defined as preoperative trials having a PD end point. RESULTS: Only 56 trials met our selection criteria. Of these, 27 trials (48%) were randomized. Forty-nine trials (88%) evaluated at least a noncytotoxic agent. In 37 trials (66%), a single agent was administered. The most prevalent tumor type was breast cancer (59%). Median duration of accrual was 28 months (range: 9-98). In these trials, there was a mean of two patients included per month (range: 0-7). The date of surgery was fixed before study entry in 35 trials (62%), while surgery was set up after preoperative therapy in the remaining 21 trials (38%). In the former trials, median duration of preoperative therapy was 17 days (range: 1-112), whereas in the latter trials it ranged from 4 to 29 weeks. The primary end point was a PD end point in 26 of the 45 trials (58%) in which it was mentioned. One percent of patients could not undergo surgery as per protocol due to an adverse event. Statistically significant predictive and PD biomarkers were identified in 17 (30%) and 27 trials (48%), respectively. CONCLUSION: Preoperative biomarkers trials are infrequent but safe and feasible. These trials often permit the identification of predictive and PD biomarkers. PMID- 26371282 TI - Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. AB - Immune checkpoint antibodies that augment the programmed cell death protein 1 (PD 1)/PD-L1 pathway have demonstrated antitumor activity across multiple malignancies, and gained recent regulatory approval as single-agent therapy for the treatment of metastatic malignant melanoma and nonsmall-cell lung cancer. Knowledge of toxicities associated with PD-1/PD-L1 blockade, as well as effective management algorithms for these toxicities, is pivotal in order to optimize clinical efficacy and safety. In this article, we review selected published and presented clinical studies investigating single-agent anti-PD-1/PD-L1 therapy and trials of combination approaches with other standard anticancer therapies, in multiple tumor types. We summarize the key adverse events reported in these studies and their management algorithms. PMID- 26371285 TI - Phase II study of single-agent cetuximab in KRAS G13D mutant metastatic colorectal cancer. PMID- 26371284 TI - Targeting the undruggable: immunotherapy meets personalized oncology in the genomic era. AB - Owing to recent advances in genomic technologies, personalized oncology is poised to fundamentally alter cancer therapy. In this paradigm, the mutational and transcriptional profiles of tumors are assessed, and personalized treatments are designed based on the specific molecular abnormalities relevant to each patient's cancer. To date, such approaches have yielded impressive clinical responses in some patients. However, a major limitation of this strategy has also been revealed: the vast majority of tumor mutations are not targetable by current pharmacological approaches. Immunotherapy offers a promising alternative to exploit tumor mutations as targets for clinical intervention. Mutated proteins can give rise to novel antigens (called neoantigens) that are recognized with high specificity by patient T cells. Indeed, neoantigen-specific T cells have been shown to underlie clinical responses to many standard treatments and immunotherapeutic interventions. Moreover, studies in mouse models targeting neoantigens, and early results from clinical trials, have established proof of concept for personalized immunotherapies targeting next-generation sequencing identified neoantigens. Here, we review basic immunological principles related to T-cell recognition of neoantigens, and we examine recent studies that use genomic data to design personalized immunotherapies. We discuss the opportunities and challenges that lie ahead on the road to improving patient outcomes by incorporating immunotherapy into the paradigm of personalized oncology. PMID- 26371286 TI - Comment on ESMO Magnitude of Clinical Benefit Scale. PMID- 26371287 TI - Fruits, vegetables and lung cancer risk: a systematic review and meta-analysis. AB - BACKGROUND: Lung cancer is the most common cause of cancer death. Fruits and vegetables containing carotenoids and other antioxidants have been hypothesized to decrease lung cancer risk. As part of the World Cancer Research Fund International Continuous Update Project, we conducted a systematic review and meta-analysis of prospective studies. METHODS: We searched PubMed and several databases up to December 2014 for prospective studies. We conducted meta-analyses comparing the highest and lowest intakes and dose-response meta-analyses to estimate summary relative risks (RRs) and 95% confidence intervals (CIs), and examine possible non-linear associations. We combined results from the Pooling Project with the studies we identified to increase the statistical power of our analysis. RESULTS: When comparing the highest with the lowest intakes, the summary RR estimates were 0.86 [95% CI 0.78-0.94; n (studies) = 18] for fruits and vegetables, 0.92 (95% CI 0.87-0.97; n = 25) for vegetables and 0.82 (95% CI 0.76-0.89; n = 29) for fruits. The association with fruit and vegetable intake was marginally significant in current smokers and inverse but not significant in former or never smokers. Significant inverse dose-response associations were observed for each 100 g/day increase: for fruits and vegetables [RR: 0.96; 95% CI 0.94-0.98, I(2) = 64%, n = 14, N (cases) = 9609], vegetables (RR: 0.94; 95% CI 0.89-0.98, I(2) = 48%, n = 20, N = 12 563) and fruits (RR: 0.92; 95% CI 0.89 0.95, I(2) = 57%, n = 23, N = 14 506). Our results were consistent among the different types of fruits and vegetables. The strength of the association differed across locations. There was evidence of a non-linear relationship (P < 0.01) between fruit and vegetable intake and lung cancer risk showing that no further benefit is obtained when increasing consumption above ~400 g per day. CONCLUSIONS: Eliminating tobacco smoking is the best strategy to prevent lung cancer. Although residual confounding by smoking cannot be ruled out, the current evidence from prospective studies is consistent with a protective role of fruit and vegetables in lung cancer aetiology. PMID- 26371289 TI - The interferon type I signature is present in systemic sclerosis before overt fibrosis and might contribute to its pathogenesis through high BAFF gene expression and high collagen synthesis. AB - BACKGROUND: Interferon (IFN) signature has been reported in definite systemic sclerosis (SSc) but it has not been characterised in early SSc (EaSSc). We aim at characterising IFN type I signature in SSc before overt skin fibrosis develops. METHODS: The expression of 11 IFN type I inducible genes was tested in whole blood samples from 30 healthy controls (HCs), 12 subjects with primary Raynaud's phenomenon (RP), 19 patients with EaSSc, 7 patients with definite SSc without cutaneous fibrosis, 21 limited cutaneous SSc and 10 diffuse cutaneous SSc subjects. The correlation between IFN activity in monocytes, B cell activating factor (BAFF) mRNA expression and type III procollagen N-terminal propeptide (PIIINP) serum levels was tested. RESULTS: In all the SSc groups, higher IFN scores were observed compared with HC. An IFN score >=7.09 discriminated HCs from patients with SSc (sensitivity=0.7, specificity=0.88, area under receiving operating characteristic (AUROC)=0.82); the prevalence of an elevated IFN score was: HC=3.3%; RP=33.3%, EaSSc=78.9%, definite SSc=100%, limited cutaneous SSc=42.9%, diffuse cutaneous SSc=70.0%. In monocytes an IFN score >=4.12 distinguished HCs from patients with fibrotic SSc (sensitivity=0.62, specificity=0.85, AUROC=0.76). Compared with IFN-negative subjects, IFN-positive subjects had higher monocyte BAFF mRNA levels (19.7+/-5.2 vs 15.20+/-4.0, p=2.1*10(-5)) and serum PIIINP levels (median=6.0 (IQR 5.4-8.9) vs median=3.9 (IQR 3.3-4.7), p=0.0004). CONCLUSIONS: An IFN type I signature is observed in patients with SSc from the earliest phases of the disease, even before overt skin fibrosis. The presence of IFN type I signature in monocytes is correlated with BAFF mRNA expression and serum PIIINP levels, supporting a contribution in the pathogenesis and progression of SSc. PMID- 26371291 TI - Composition of fungal soil communities varies with plant abundance and geographic origin. AB - Interactions of belowground fungal communities with exotic and native plant species may be important drivers of plant community structure in invaded grasslands. However, field surveys linking plant community structure with belowground fungal communities are missing. We investigated whether a selected number of abundant and relatively rare plants, either native or exotic, from an old-field site associate with different fungal communities. We also assessed whether these plants showed different symbiotic relationships with soil biota through their roots. We characterized the plant community and collected roots to investigate fungal communities using 454 pyrosequencing and assessed arbuscular mycorrhizal colonization and enemy-induced lesions. Differences in fungal communities were considered based on the assessment of alpha- and beta diversity depending on plant 'abundance' and 'origin'. Plant abundance and origin determined the fungal community. Fungal richness was higher for native abundant as opposed to relatively rare native plant species. However, this was not observed for exotics of contrasting abundance. Regardless of their origin, beta diversity was higher for rare than for abundant species. Abundant exotics in the community, which happen to be grasses, were the least mycorrhizal whereas rare natives were most susceptible to enemy attack. Our results suggest that compared with exotics, the relative abundance of remnant native plant species in our old field site is still linked to the structure of belowground fungal communities. In contrast, exotic species may act as a disturbing agent contributing towards the homogenization of soil fungal communities, potentially changing feedback interactions. PMID- 26371288 TI - Guidelines for the definition of time-to-event end points in renal cell cancer clinical trials: results of the DATECAN project?. AB - BACKGROUND: In clinical trials, the use of intermediate time-to-event end points (TEEs) is increasingly common, yet their choice and definitions are not standardized. This limits the usefulness for comparing treatment effects between studies. The aim of the DATECAN Kidney project is to clarify and recommend definitions of TEE in renal cell cancer (RCC) through a formal consensus method for end point definitions. MATERIALS AND METHODS: A formal modified Delphi method was used for establishing consensus. From a 2006-2009 literature review, the Steering Committee (SC) selected 9 TEE and 15 events in the nonmetastatic (NM) and metastatic/advanced (MA) RCC disease settings. Events were scored on the range of 1 (totally disagree to include) to 9 (totally agree to include) in the definition of each end point. Rating Committee (RC) experts were contacted for the scoring rounds. From these results, final recommendations were established for selecting pertinent end points and the associated events. RESULTS: Thirty four experts scored 121 events for 9 end points. Consensus was reached for 31%, 43% and 85% events during the first, second and third rounds, respectively. The expert recommend the use of three and two endpoints in NM and MA setting, respectively. In the NM setting: disease-free survival (contralateral RCC, appearance of metastases, local or regional recurrence, death from RCC or protocol treatment), metastasis-free survival (appearance of metastases, regional recurrence, death from RCC); and local-regional-free survival (local or regional recurrence, death from RCC). In the MA setting: kidney cancer-specific survival (death from RCC or protocol treatment) and progression-free survival (death from RCC, local, regional, or metastatic progression). CONCLUSIONS: The consensus method revealed that intermediate end points have not been well defined, because all of the selected end points had at least one event definition for which no consensus was obtained. These clarified definitions of TEE should become standard practice in all RCC clinical trials, thus facilitating reporting and increasing precision in between trial comparisons. PMID- 26371292 TI - Fishing for nutrients in heterogeneous landscapes: modelling plant growth trade offs in monocultures and mixed communities. AB - The problem of how best to find and exploit essential resources, the quality and locations of which are unknown, is common throughout biology. For plants, the need to grow an efficient root system so as to acquire patchily distributed soil nutrients is typically complicated by competition between plants, and by the costs of maintaining the root system. Simple mechanistic models for root growth can help elucidate these complications, and here we argue that these models can be usefully informed by models initially developed for foraging fish larvae. Both plant and fish need to efficiently search a spatio-temporally variable environment using simple algorithms involving only local information, and both must perform this task against a backdrop of intra- and inter-specific competition and background mortality. Here we develop these parallels by using simple stochastic models describing the growth and efficiency of four contrasting idealized root growth strategies. We show that plants which grow identically in isolation in homogeneous substrates will typically perform very differently when grown in monocultures, in heterogeneous nutrient landscapes and in mixed-species competition. In particular, our simulations show a consistent result that plants which trade-off rapid growth in favour of a more efficient and durable root system perform better, both on average and in terms of the best performing individuals, than more rapidly growing ephemeral root systems. Moreover, when such slower growing but more efficient plants are grown in competition, the overall community productivity can exceed that of the constituent monocultures. These findings help to disentangle many of the context-dependent behaviours seen in the experimental literature, and may form a basis for future studies at the level of complex population dynamics and life history evolution. PMID- 26371293 TI - Delayed relapse in pseudotumor cerebri due to new stenosis after transverse sinus stenting. AB - A patient presented with recurrent severe pseudotumor cerebri (PTC). Transverse sinus stenting is a very effective treatment option, however stenosis and intracranial hypertension can recur. In our patient, stenting initially resulted in resolution of papilloedema. However, after 5 years, a new stenosis developed which required further stenting. This case highlights the fact that, in patients with PTC who undergo transverse sinus stenting, a small proportion require repeat treatment due to formation of a new stenosis, usually adjacent to the existing stent. Patients with severe disease, such as ours, may be at higher risk of recurrence. Regardless of the severity, all patients who undergo stenting should have regular ocular follow-up. PMID- 26371294 TI - Hemodynamics during anesthesia for intra-arterial therapy of acute ischemic stroke. AB - BACKGROUND AND PURPOSE: Many studies have suggested a relationship between the type of anesthesia provided during intra-arterial therapy for acute ischemic stroke and patient outcomes. Variability in blood pressure and hypotension have previously been identified as possible reasons for worse outcomes in acute stroke. Our aim was to investigate hemodynamic parameters and neurological outcomes of patients receiving either general anesthesia or conscious sedation for intra-arterial therapy of acute stroke. METHODS: We performed a retrospective review of patients undergoing intra-arterial therapy from December 2008 to March 2015. Demographic data, baseline National Institutes of Health Stroke Scale score, preoperative physiological variables, procedural details, systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate, and modified Rankin Scale scores were recorded. RESULTS: 99 patients were included in the study, with 38 receiving general anesthesia and 61 receiving conscious sedation. Patients who received general anesthesia had a lower maximum SBP (p=0.02), minimum SBP (p<0.0001), minimum DBP (p<0.0001), and minimum MAP (p<0.0001). On multivariate analysis, general anesthesia was associated with lower minimum SBP (p=0.04), DBP (p=0.02), and MAP (p=0.007). Conscious sedation was associated with more favorable neurological outcomes (p=0.02). Patients with favorable neurological outcomes had a lower maximum variability in SBP (p=0.01) and MAP (p=0.03), as well as a higher minimum DBP (p=0.03). CONCLUSIONS: Patients with acute ischemic stroke undergoing intra-arterial therapy with general anesthesia had lower minimum SBP, DBP, and MAP, greater fluctuations in blood pressure, and less favorable outcomes. More studies are needed to examine the implications of variable and reduced blood pressures and neurological outcomes. PMID- 26371295 TI - Initial factors affecting the clinical outcome after successful recanalization via MR-based mechanical thrombectomy in patients with acute ischemic stroke due to basilar artery occlusion. AB - BACKGROUND AND PURPOSE: To determine the initial factors, including patient characteristics, stroke etiology and severity, time factors, and imaging findings, that could affect the clinical outcome of patients with acute ischemic stroke (AIS) caused by basilar artery occlusion (BAO) where successful recanalization was achieved via mechanical thrombectomy. METHODS: Between March 2011 and December 2014, 35 patients with AIS caused by BAO received MRI/MR angiography-based mechanical thrombectomies, and recanalization was achieved with a Thrombolysis In Cerebral Infarction score of >2b. The patients were divided into a good outcome group (n=19), defined as those with a modified Rankin Scale (mRS) score of 0-2 at 3 months after stroke onset, and a poor outcome group (n=16), defined as a mRS score of 3-6. The differences between the groups were analyzed. RESULTS: Initial National Institutes of Health Stroke Scale (NIHSS) score (good vs poor: 17.9+/-8.9 vs 27.6+/-8.5, p=0.003), posterior circulation Acute Stroke Prognosis Early CT Score (pc-ASPECTS) based on initial diffusion weighted images (DWI) (good vs poor: 7.8+/-1.6 vs 5.4+/-1.8, p=0.001), pc-ASPECTS based on contrast staining on the post-thrombectomy control CT (good vs poor: 9.2+/-1.5 vs 6.3+/-2.2, p<0.001), and presence of contrast staining in the brainstem on that CT (good vs poor: 15.8% vs 81.6%, p<0.001) were significantly different between the groups. CONCLUSIONS: Patients with AIS caused by BAO with a lower initial NIHSS score, fewer lesions on initial DWI, and less contrast staining on the post-thrombectomy control CT have higher probabilities of a good clinical outcome after successful recanalization via a mechanical thrombectomy. PMID- 26371296 TI - On regreening and degradation in Sahelian watersheds. AB - Over many decades our understanding of the impacts of intermittent drought in water-limited environments like the West African Sahel has been influenced by a narrative of overgrazing and human-induced desertification. The desertification narrative has persisted in both scientific and popular conception, such that recent regional-scale recovery ("regreening") and local success stories (community-led conservation efforts) in the Sahel, following the severe droughts of the 1970s-1980s, are sometimes ignored. Here we report a study of watershed scale vegetation dynamics in 260 watersheds, sampled in four regions of Senegal, Mali, and Niger from 1983-2012, using satellite-derived vegetation indices as a proxy for net primary production. In response to earlier controversy, we first examine the shape of the rainfall-net primary production relationship and how it impacts conclusions regarding greening or degradation. We conclude that the choice of functional relationship has little quantitative impact on our ability to infer greening or degradation trends. We then present an approach to analyze changes in long-term (decade-scale) average rain-use efficiency (an indicator of slowly responding vegetation structural changes) relative to changes in interannual-scale rainfall sensitivity (an indicator of landscape ability to respond rapidly to rainfall variability) to infer trends in greening/degradation of the watersheds in our sample regions. The predominance of increasing rain-use efficiency in our data supports earlier reports of a "greening" trend across the Sahel. However, there are strong regional differences in the extent and direction of change, and in the apparent role of changing woody and herbaceous components in driving those temporal trends. PMID- 26371297 TI - Structure of subcomplex Ibeta of mammalian respiratory complex I leads to new supernumerary subunit assignments. AB - Mitochondrial complex I (proton-pumping NADH:ubiquinone oxidoreductase) is an essential respiratory enzyme. Mammalian complex I contains 45 subunits: 14 conserved "core" subunits and 31 "supernumerary" subunits. The structure of Bos taurus complex I, determined to 5-A resolution by electron cryomicroscopy, described the structure of the mammalian core enzyme and allowed the assignment of 14 supernumerary subunits. Here, we describe the 6.8-A resolution X-ray crystallography structure of subcomplex Ibeta, a large portion of the membrane domain of B. taurus complex I that contains two core subunits and a cohort of supernumerary subunits. By comparing the structures and composition of subcomplex Ibeta and complex I, supported by comparisons with Yarrowia lipolytica complex I, we propose assignments for eight further supernumerary subunits in the structure. Our new assignments include two CHCH-domain containing subunits that contain disulfide bridges between CX9C motifs; they are processed by the Mia40 oxidative folding pathway in the intermembrane space and probably stabilize the membrane domain. We also assign subunit B22, an LYR protein, to the matrix face of the membrane domain. We reveal that subunit B22 anchors an acyl carrier protein (ACP) to the complex, replicating the LYR protein-ACP structural module that was identified previously in the hydrophilic domain. Thus, we significantly extend knowledge of how the mammalian supernumerary subunits are arranged around the core enzyme, and provide insights into their roles in biogenesis and regulation. PMID- 26371298 TI - Strong upslope shifts in Chimborazo's vegetation over two centuries since Humboldt. AB - Global climate change is driving species poleward and upward in high-latitude regions, but the extent to which the biodiverse tropics are similarly affected is poorly known due to a scarcity of historical records. In 1802, Alexander von Humboldt ascended the Chimborazo volcano in Ecuador. He recorded the distribution of plant species and vegetation zones along its slopes and in surrounding parts of the Andes. We revisited Chimborazo in 2012, precisely 210 y after Humboldt's expedition. We documented upward shifts in the distribution of vegetation zones as well as increases in maximum elevation limits of individual plant taxa of >500 m on average. These range shifts are consistent with increased temperatures and glacier retreat on Chimborazo since Humboldt's study. Our findings provide evidence that global warming is strongly reshaping tropical plant distributions, consistent with Humboldt's proposal that climate is the primary control on the altitudinal distribution of vegetation. PMID- 26371299 TI - Protecting group-free, selective cross-coupling of alkyltrifluoroborates with borylated aryl bromides via photoredox/nickel dual catalysis. AB - Orthogonal reactivity modes offer substantial opportunities for rapid construction of complex small molecules. However, most strategies for imparting orthogonality to cross-coupling reactions rely on differential protection of reactive sites, greatly reducing both atom and step economies. Reported here is a strategy for orthogonal cross-coupling wherein a mechanistically distinct activation mode for transmetalation of sp(3)-hybridized organoboron reagents enables C-C bond formation in the presence of various protected and unprotected sp(2)-hybridized organoborons. This manifold has the potential for broad application, because orthogonality is inherent to the activation mode itself. The diversification potential of this platform is shown in the rapid elaboration of a trifunctional lynchpin through various transition metal-catalyzed processes without nonproductive deprotection or functional group manipulation steps. PMID- 26371300 TI - Backward multiple imputation estimation of the conditional lifetime expectancy function with application to censored human longevity data. AB - The conditional lifetime expectancy function (LEF) is the expected lifetime of a subject given survival past a certain time point and the values of a set of explanatory variables. This function is attractive to researchers because it summarizes the entire residual life distribution and has an easy interpretation compared with the popularly used hazard function. In this paper, we propose a general framework of backward multiple imputation for estimating the conditional LEF and the variance of the estimator in the right-censoring setting. Simulation studies are conducted to investigate the empirical properties of the proposed estimator and the corresponding variance estimator. We demonstrate the method on the Beaver Dam Eye Study data, where the expected human lifetime is modeled with smoothing-spline ANOVA given the covariates information including sex, lifestyle factors, and disease variables. PMID- 26371301 TI - Synthetic dosage lethality in the human metabolic network is highly predictive of tumor growth and cancer patient survival. AB - Synthetic dosage lethality (SDL) denotes a genetic interaction between two genes whereby the underexpression of gene A combined with the overexpression of gene B is lethal. SDLs offer a promising way to kill cancer cells by inhibiting the activity of SDL partners of activated oncogenes in tumors, which are often difficult to target directly. As experimental genome-wide SDL screens are still scarce, here we introduce a network-level computational modeling framework that quantitatively predicts human SDLs in metabolism. For each enzyme pair (A, B) we systematically knock out the flux through A combined with a stepwise flux increase through B and search for pairs that reduce cellular growth more than when either enzyme is perturbed individually. The predictive signal of the emerging network of 12,000 SDLs is demonstrated in five different ways. (i) It can be successfully used to predict gene essentiality in shRNA cancer cell line screens. Moving to clinical tumors, we show that (ii) SDLs are significantly underrepresented in tumors. Furthermore, breast cancer tumors with SDLs active (iii) have smaller sizes and (iv) result in increased patient survival, indicating that activation of SDLs increases cancer vulnerability. Finally, (v) patient survival improves when multiple SDLs are present, pointing to a cumulative effect. This study lays the basis for quantitative identification of cancer SDLs in a model-based mechanistic manner. The approach presented can be used to identify SDLs in species and cell types in which "omics" data necessary for data-driven identification are missing. PMID- 26371302 TI - Bantu expansion shows that habitat alters the route and pace of human dispersals. AB - Unlike most other biological species, humans can use cultural innovations to occupy a range of environments, raising the intriguing question of whether human migrations move relatively independently of habitat or show preferences for familiar ones. The Bantu expansion that swept out of West Central Africa beginning ~5,000 y ago is one of the most influential cultural events of its kind, eventually spreading over a vast geographical area a new way of life in which farming played an increasingly important role. We use a new dated phylogeny of ~400 Bantu languages to show that migrating Bantu-speaking populations did not expand from their ancestral homeland in a "random walk" but, rather, followed emerging savannah corridors, with rainforest habitats repeatedly imposing temporal barriers to movement. When populations did move from savannah into rainforest, rates of migration were slowed, delaying the occupation of the rainforest by on average 300 y, compared with similar migratory movements exclusively within savannah or within rainforest by established rainforest populations. Despite unmatched abilities to produce innovations culturally, unfamiliar habitats significantly alter the route and pace of human dispersals. PMID- 26371303 TI - Integration of high-content screening and untargeted metabolomics for comprehensive functional annotation of natural product libraries. AB - Traditional natural products discovery using a combination of live/dead screening followed by iterative bioassay-guided fractionation affords no information about compound structure or mode of action until late in the discovery process. This leads to high rates of rediscovery and low probabilities of finding compounds with unique biological and/or chemical properties. By integrating image-based phenotypic screening in HeLa cells with high-resolution untargeted metabolomics analysis, we have developed a new platform, termed Compound Activity Mapping, that is capable of directly predicting the identities and modes of action of bioactive constituents for any complex natural product extract library. This new tool can be used to rapidly identify novel bioactive constituents and provide predictions of compound modes of action directly from primary screening data. This approach inverts the natural products discovery process from the existing "grind and find" model to a targeted, hypothesis-driven discovery model where the chemical features and biological function of bioactive metabolites are known early in the screening workflow, and lead compounds can be rationally selected based on biological and/or chemical novelty. We demonstrate the utility of the Compound Activity Mapping platform by combining 10,977 mass spectral features and 58,032 biological measurements from a library of 234 natural products extracts and integrating these two datasets to identify 13 clusters of fractions containing 11 known compound families and four new compounds. Using Compound Activity Mapping we discovered the quinocinnolinomycins, a new family of natural products with a unique carbon skeleton that cause endoplasmic reticulum stress. PMID- 26371304 TI - Bats initiate vital agroecological interactions in corn. AB - In agroecosystems worldwide, bats are voracious predators of crop pests and may provide services to farmers worth billions of U.S. dollars. However, such valuations make untested assumptions about the ecological effect of bats in agroecosystems. Specifically, estimates of the value of pest suppression services assume bats consume sufficient numbers of crop pests to affect impact pest reproduction and subsequent damage to crops. Corn is an essential crop for farmers, and is grown on more than 150 million hectares worldwide. Using large exclosures in corn fields, we show that bats exert sufficient pressure on crop pests to suppress larval densities and damage in this cosmopolitan crop. In addition, we show that bats suppress pest-associated fungal growth and mycotoxin in corn. We estimate the suppression of herbivory by insectivorous bats is worth more than 1 billion USD globally on this crop alone, and bats may further benefit farmers by indirectly suppressing pest-associated fungal growth and toxic compounds on corn. Bats face a variety of threats globally, but their relevance as predators of insects in ubiquitous corn-dominated landscapes underlines the economic and ecological importance of conserving biodiversity. PMID- 26371305 TI - Musical expertise is related to altered functional connectivity during audiovisual integration. AB - The present study investigated the cortical large-scale functional network underpinning audiovisual integration via magnetoencephalographic recordings. The reorganization of this network related to long-term musical training was investigated by comparing musicians to nonmusicians. Connectivity was calculated on the basis of the estimated mutual information of the sources' activity, and the corresponding networks were statistically compared. Nonmusicians' results indicated that the cortical network associated with audiovisual integration supports visuospatial processing and attentional shifting, whereas a sparser network, related to spatial awareness supports the identification of audiovisual incongruences. In contrast, musicians' results showed enhanced connectivity in regions related to the identification of auditory pattern violations. Hence, nonmusicians rely on the processing of visual clues for the integration of audiovisual information, whereas musicians rely mostly on the corresponding auditory information. The large-scale cortical network underpinning multisensory integration is reorganized due to expertise in a cognitive domain that largely involves audiovisual integration, indicating long-term training-related neuroplasticity. PMID- 26371306 TI - Targeted, activity-dependent spinal stimulation produces long-lasting motor recovery in chronic cervical spinal cord injury. AB - Use-dependent movement therapies can lead to partial recovery of motor function after neurological injury. We attempted to improve recovery by developing a neuroprosthetic intervention that enhances movement therapy by directing spike timing-dependent plasticity in spared motor pathways. Using a recurrent neural computer interface in rats with a cervical contusion of the spinal cord, we synchronized intraspinal microstimulation below the injury with the arrival of functionally related volitional motor commands signaled by muscle activity in the impaired forelimb. Stimulation was delivered during physical retraining of a forelimb behavior and throughout the day for 3 mo. Rats receiving this targeted, activity-dependent spinal stimulation (TADSS) exhibited markedly enhanced recovery compared with animals receiving targeted but open-loop spinal stimulation and rats receiving physical retraining alone. On a forelimb reach and grasp task, TADSS animals recovered 63% of their preinjury ability, more than two times the performance level achieved by the other therapy groups. Therapeutic gains were maintained for 3 additional wk without stimulation. The results suggest that activity-dependent spinal stimulation can induce neural plasticity that improves behavioral recovery after spinal cord injury. PMID- 26371307 TI - Magnesium pyrophosphates in enzyme mimics of nucleotide synthases and kinases and in their prebiotic chemistry. AB - Derivatives of ribosyl pyrophosphate have been synthesized, and examined with magnesium salts in the coupling of the ribose unit to various nucleophiles, including pyrazole and 2-chloroimidazole. Only with the magnesium salt present did they generate the ribosyl cation by binding to the leaving group and then couple the ribose derivative with nucleophiles. The role of magnesium salts in phosphorylation of methanol by ATP was also examined. Here a remarkable effect was seen: phosphorylation by ATP was slowed with low concentrations of Mg(2+) but accelerated by higher concentrations. Related effects were also seen in the effect of Mg(2+) on phosphorylation by ADP. The likely mechanisms explain these effects. PMID- 26371308 TI - Dietary change among hominins and cercopithecids in Ethiopia during the early Pliocene. AB - The incorporation of C4 resources into hominin diet signifies increased dietary breadth within hominins and divergence from the dietary patterns of other great apes. Morphological evidence indicates that hominin diet became increasingly diverse by 4.2 million years ago but may not have included large proportions of C4 foods until 800 thousand years later, given the available isotopic evidence. Here we use carbon isotope data from early to mid Pliocene hominin and cercopithecid fossils from Woranso-Mille (central Afar, Ethiopia) to constrain the timing of this dietary change and its ecological context. We show that both hominins and some papionins expanded their diets to include C4 resources as early as 3.76 Ma. Among hominins, this dietary expansion postdates the major dentognathic morphological changes that distinguish Australopithecus from Ardipithecus, but it occurs amid a continuum of adaptations to diets of tougher, harder foods and to committed terrestrial bipedality. In contrast, carbon isotope data from cercopithecids indicate that C4-dominated diets of the earliest members of the Theropithecus oswaldi lineage preceded the dental specialization for grazing but occurred after they were fully terrestrial. The combined data indicate that the inclusion of C4 foods in hominin diet occurred as part of broader ecological changes in African primate communities. PMID- 26371310 TI - Climate change and physical disturbance cause similar community shifts in biological soil crusts. AB - Biological soil crusts (biocrusts)-communities of mosses, lichens, cyanobacteria, and heterotrophs living at the soil surface-are fundamental components of drylands worldwide, and destruction of biocrusts dramatically alters biogeochemical processes, hydrology, surface energy balance, and vegetation cover. Although there has been long-standing concern over impacts of physical disturbances on biocrusts (e.g., trampling by livestock, damage from vehicles), there is increasing concern over the potential for climate change to alter biocrust community structure. Using long-term data from the Colorado Plateau, we examined the effects of 10 y of experimental warming and altered precipitation (in full-factorial design) on biocrust communities and compared the effects of altered climate with those of long-term physical disturbance (>10 y of replicated human trampling). Surprisingly, altered climate and physical disturbance treatments had similar effects on biocrust community structure. Warming, altered precipitation frequency [an increase of small (1.2 mm) summer rainfall events], and physical disturbance from trampling all promoted early successional community states marked by dramatic declines in moss cover and increases in cyanobacteria cover, with more variable effects on lichens. Although the pace of community change varied significantly among treatments, our results suggest that multiple aspects of climate change will affect biocrusts to the same degree as physical disturbance. This is particularly disconcerting in the context of warming, as temperatures for drylands are projected to increase beyond those imposed as treatments in our study. PMID- 26371309 TI - Creation of a histone deacetylase 6 inhibitor and its biological effects [corrected]. AB - We report the development of a potent, selective histone deacetylase 6 (HDAC6) inhibitor. This HDAC6 inhibitor blocks growth of normal and transformed cells but does not induce death of normal cells. The HDAC6 inhibitor alone is as effective as paclitaxel in anticancer activity in tumor-bearing mice. PMID- 26371311 TI - Zwitterionic gel encapsulation promotes protein stability, enhances pharmacokinetics, and reduces immunogenicity. AB - Advances in protein therapy are hindered by the poor stability, inadequate pharmacokinetic (PK) profiles, and immunogenicity of many therapeutic proteins. Polyethylene glycol conjugation (PEGylation) is the most successful strategy to date to overcome these shortcomings, and more than 10 PEGylated proteins have been brought to market. However, anti-PEG antibodies induced by treatment raise serious concerns about the future of PEGylated therapeutics. Here, we demonstrate a zwitterionic polymer network encapsulation technology that effectively enhances protein stability and PK while mitigating the immune response. Uricase modified with a comprehensive zwitterionic polycarboxybetaine (PCB) network exhibited exceptional stability and a greatly prolonged circulation half-life. More importantly, the PK behavior was unchanged, and neither anti-uricase nor anti-PCB antibodies were detected after three weekly injections in a rat model. This technology is applicable to a variety of proteins and unlocks the possibility of adopting highly immunogenic proteins for therapeutic or protective applications. PMID- 26371312 TI - Role of water and steric constraints in the kinetics of cavity-ligand unbinding. AB - A key factor influencing a drug's efficacy is its residence time in the binding pocket of the host protein. Using atomistic computer simulation to predict this residence time and the associated dissociation process is a desirable but extremely difficult task due to the long timescales involved. This gets further complicated by the presence of biophysical factors such as steric and solvation effects. In this work, we perform molecular dynamics (MD) simulations of the unbinding of a popular prototypical hydrophobic cavity-ligand system using a metadynamics-based approach that allows direct assessment of kinetic pathways and parameters. When constrained to move in an axial manner, the unbinding time is found to be on the order of 4,000 s. In accordance with previous studies, we find that the cavity must pass through a region of sharp wetting transition manifested by sudden and high fluctuations in solvent density. When we remove the steric constraints on ligand, the unbinding happens predominantly by an alternate pathway, where the unbinding becomes 20 times faster, and the sharp wetting transition instead becomes continuous. We validate the unbinding timescales from metadynamics through a Poisson analysis, and by comparison through detailed balance to binding timescale estimates from unbiased MD. This work demonstrates that enhanced sampling can be used to perform explicit solvent MD studies at timescales previously unattainable, to our knowledge, obtaining direct and reliable pictures of the underlying physiochemical factors including free energies and rate constants. PMID- 26371313 TI - Genetic variation in CD38 and breastfeeding experience interact to impact infants' attention to social eye cues. AB - Attending to emotional information conveyed by the eyes is an important social skill in humans. The current study examined this skill in early development by measuring attention to eyes while viewing emotional faces in 7-mo-old infants. In particular, we investigated individual differences in infant attention to eyes in the context of genetic variation (CD38 rs3796863 polymorphism) and experiential variation (exclusive breastfeeding duration) related to the oxytocin system. Our results revealed that, whereas infants at this age show a robust fear bias (increased attention to fearful eyes), their attention to angry and happy eyes varies as a function of exclusive breastfeeding experience and genetic variation in CD38. Specifically, extended exclusive breastfeeding duration selectively enhanced looking preference to happy eyes and decreased looking to angry eyes. Importantly, however, this interaction was impacted by CD38 variation, such that only the looking preferences of infants homozygous for the C allele of rs3796863 were affected by breastfeeding experience. This genotype has been associated with reduced release of oxytocin and higher rates of autism. In contrast, infants with the CA/AA genotype showed similar looking preferences regardless of breastfeeding exposure. Thus, differences in the sensitivity to emotional eyes may be linked to an interaction between the endogenous (CD38) and exogenous (breastfeeding) availability of oxytocin. These findings underline the importance of maternal care and the oxytocin system in contributing to the early development of responding to social eye cues. PMID- 26371314 TI - The B-cell antigen receptor integrates adaptive and innate immune signals. AB - B cells respond to antigens by engagement of their B-cell antigen receptor (BCR) and of coreceptors through which signals from helper T cells or pathogen associated molecular patterns are delivered. We show that the proliferative response of B cells to the latter stimuli is controlled by BCR-dependent activation of phosphoinositidyl 3-kinase (PI-3K) signaling. Glycogen synthase kinase 3beta and Foxo1 are two PI-3K-regulated targets that play important roles, but to different extents, depending on the specific mitogen. These results suggest a model for integrating signals from the innate and the adaptive immune systems in the control of the B-cell immune response. PMID- 26371315 TI - Regional centromeres in the yeast Candida lusitaniae lack pericentromeric heterochromatin. AB - Point centromeres are specified by a short consensus sequence that seeds kinetochore formation, whereas regional centromeres lack a conserved sequence and instead are epigenetically inherited. Regional centromeres are generally flanked by heterochromatin that ensures high levels of cohesin and promotes faithful chromosome segregation. However, it is not known whether regional centromeres require pericentromeric heterochromatin. In the yeast Candida lusitaniae, we identified a distinct type of regional centromere that lacks pericentromeric heterochromatin. Centromere locations were determined by ChIP-sequencing of two key centromere proteins, Cse4 and Mif2, and are consistent with bioinformatic predictions. The centromeric DNA sequence was unique for each chromosome and spanned 4-4.5 kbp, consistent with regional epigenetically inherited centromeres. However, unlike other regional centromeres, there was no evidence of pericentromeric heterochromatin in C. lusitaniae. In particular, flanking genes were expressed at a similar level to the rest of the genome, and a URA3 reporter inserted adjacent to a centromere was not repressed. In addition, regions flanking the centromeric core were not associated with hypoacetylated histones or a sirtuin deacetylase that generates heterochromatin in other yeast. Interestingly, the centromeric chromatin had a distinct pattern of histone modifications, being enriched for methylated H3K79 and H3R2 but lacking methylation of H3K4, which is found at other regional centromeres. Thus, not all regional centromeres require flanking heterochromatin. PMID- 26371316 TI - Signal strength regulates antigen-mediated T-cell deceleration by distinct mechanisms to promote local exploration or arrest. AB - T lymphocytes are highly motile cells that decelerate upon antigen recognition. These cells can either completely stop or maintain a low level of motility, forming contacts referred to as synapses or kinapses, respectively. Whether similar or distinct molecular mechanisms regulate T-cell deceleration during synapses or kinapses is unclear. Here, we used microfabricated channels and intravital imaging to observe and manipulate T-cell kinapses and synapses. We report that high-affinity antigen induced a pronounced deceleration selectively dependent on Ca(2+) signals and actin-related protein 2/3 complex (Arp2/3) activity. In contrast, low-affinity antigens induced a switch of migration mode that promotes T-cell exploratory behavior, characterized by partial deceleration and frequent direction changes. This switch depended on T-cell receptor binding but was largely independent of downstream signaling. We propose that distinct mechanisms of T-cell deceleration can be triggered during antigenic recognition to favor local exploration and signal integration upon suboptimal stimulus and complete arrest on the best antigen-presenting cells. PMID- 26371317 TI - Melting of iron determined by X-ray absorption spectroscopy to 100 GPa. AB - Temperature, thermal history, and dynamics of Earth rely critically on the knowledge of the melting temperature of iron at the pressure conditions of the inner core boundary (ICB) where the geotherm crosses the melting curve. The literature on this subject is overwhelming, and no consensus has been reached, with a very large disagreement of the order of 2,000 K for the ICB temperature. Here we report new data on the melting temperature of iron in a laser-heated diamond anvil cell to 103 GPa obtained by X-ray absorption spectroscopy, a technique rarely used at such conditions. The modifications of the onset of the absorption spectra are used as a reliable melting criterion regardless of the solid phase from which the solid to liquid transition takes place. Our results show a melting temperature of iron in agreement with most previous studies up to 100 GPa, namely of 3,090 K at 103 GPa. PMID- 26371318 TI - Lhx2 regulates the timing of beta-catenin-dependent cortical neurogenesis. AB - The timing of cortical neurogenesis has a major effect on the size and organization of the mature cortex. The deletion of the LIM-homeodomain transcription factor Lhx2 in cortical progenitors by Nestin-cre leads to a dramatically smaller cortex. Here we report that Lhx2 regulates the cortex size by maintaining the cortical progenitor proliferation and delaying the initiation of neurogenesis. The loss of Lhx2 in cortical progenitors results in precocious radial glia differentiation and a temporal shift of cortical neurogenesis. We further investigated the underlying mechanisms at play and demonstrated that in the absence of Lhx2, the Wnt/beta-catenin pathway failed to maintain progenitor proliferation. We developed and applied a mathematical model that reveals how precocious neurogenesis affected cortical surface and thickness. Thus, we concluded that Lhx2 is required for beta-catenin function in maintaining cortical progenitor proliferation and controls the timing of cortical neurogenesis. PMID- 26371319 TI - Complex constraints on allometry revealed by artificial selection on the wing of Drosophila melanogaster. AB - Precise exponential scaling with size is a fundamental aspect of phenotypic variation. These allometric power laws are often invariant across taxa and have long been hypothesized to reflect developmental constraints. Here we test this hypothesis by investigating the evolutionary potential of an allometric scaling relationship in drosophilid wing shape that is nearly invariant across 111 species separated by at least 50 million years of evolution. In only 26 generations of artificial selection in a population of Drosophila melanogaster, we were able to drive the allometric slope to the outer range of those found among the 111 sampled species. This response was rapidly lost when selection was suspended. Only a small proportion of this reversal could be explained by breakup of linkage disequilibrium, and direct selection on wing shape is also unlikely to explain the reversal, because the more divergent wing shapes produced by selection on the allometric intercept did not revert. We hypothesize that the reversal was instead caused by internal selection arising from pleiotropic links to unknown traits. Our results also suggest that the observed selection response in the allometric slope was due to a component expressed late in larval development and that variation in earlier development did not respond to selection. Together, these results are consistent with a role for pleiotropic constraints in explaining the remarkable evolutionary stability of allometric scaling. PMID- 26371320 TI - Correction to Supporting Information for Markowitz et al., Multiple component networks support working memory in prefrontal cortex. PMID- 26371321 TI - Amelioration of inflammation and tissue damage in sickle cell model mice by Nrf2 activation. AB - Sickle cell disease (SCD) is an inherited disorder caused by a point mutation in the beta-globin gene, leading to the production of abnormally shaped red blood cells. Sickle cells are prone to hemolysis and thereby release free heme into plasma, causing oxidative stress and inflammation that in turn result in damage to multiple organs. The transcription factor Nrf2 (nuclear factor erythroid 2 related factor 2) is a master regulator of the antioxidant cell-defense system. Here we show that constitutive Nrf2 activation by ablation of its negative regulator Keap1 (kelch-like ECH-associated protein 1) significantly improves symptoms in SCD model mice. SCD mice exhibit severe liver damage and lung inflammation associated with high expression levels of proinflammatory cytokines and adhesion molecules compared with normal mice. Importantly, these symptoms subsided after Nrf2 activation. Although hemolysis and stress erythropoiesis did not change substantially in the Nrf2-activated SCD mice, Nrf2 promoted the elimination of plasma heme released by sickle cells' hemolysis and thereby reduced oxidative stress and inflammation, demonstrating that Nrf2 activation reduces organ damage and segregates inflammation from prevention of hemolysis in SCD mice. Furthermore, administration of the Nrf2 inducer CDDO-Im (2-cyano-3, 12 dioxooleana-1, 9 diene-28-imidazolide) also relieved inflammation and organ failure in SCD mice. These results support the contention that Nrf2 induction may be an important means to protect organs from the pathophysiology of sickle cell induced damage. PMID- 26371322 TI - MYB36 regulates the transition from proliferation to differentiation in the Arabidopsis root. AB - Stem cells are defined by their ability to self-renew and produce daughter cells that proliferate and mature. These maturing cells transition from a proliferative state to a terminal state through the process of differentiation. In the Arabidopsis thaliana root the transcription factors SCARECROW and SHORTROOT regulate specification of the bipotent stem cell that gives rise to cortical and endodermal progenitors. Subsequent progenitor proliferation and differentiation generate mature endodermis, marked by the Casparian strip, a cell-wall modification that prevents ion diffusion into and out of the vasculature. We identified a transcription factor, MYB DOMAIN PROTEIN 36 (MYB36), that regulates the transition from proliferation to differentiation in the endodermis. We show that SCARECROW directly activates MYB36 expression, and that MYB36 likely acts in a feed-forward loop to regulate essential Casparian strip formation genes. We show that myb36 mutants have delayed and defective barrier formation as well as extra divisions in the meristem. Our results demonstrate that MYB36 is a critical positive regulator of differentiation and negative regulator of cell proliferation. PMID- 26371323 TI - EBS7 is a plant-specific component of a highly conserved endoplasmic reticulum associated degradation system in Arabidopsis. AB - Endoplasmic reticulum (ER)-associated degradation (ERAD) is an essential part of an ER-localized protein quality-control system for eliminating terminally misfolded proteins. Recent studies have demonstrated that the ERAD machinery is conserved among yeast, animals, and plants; however, it remains unknown if the plant ERAD system involves plant-specific components. Here we report that the Arabidopsis ethyl methanesulfonate-mutagenized brassinosteroid-insensitive 1 suppressor 7 (EBS7) gene encodes an ER membrane-localized ERAD component that is highly conserved in land plants. Loss-of-function ebs7 mutations prevent ERAD of brassinosteroid insensitive 1-9 (bri1-9) and bri1-5, two ER-retained mutant variants of the cell-surface receptor for brassinosteroids (BRs). As a result, the two mutant receptors accumulate in the ER and consequently leak to the plasma membrane, resulting in the restoration of BR sensitivity and phenotypic suppression of the bri1-9 and bri1-5 mutants. EBS7 accumulates under ER stress, and its mutations lead to hypersensitivity to ER and salt stresses. EBS7 interacts with the ER membrane-anchored ubiquitin ligase Arabidopsis thaliana HMG CoA reductase degradation 1a (AtHrd1a), one of the central components of the Arabidopsis ERAD machinery, and an ebs7 mutation destabilizes AtHrd1a to reduce polyubiquitination of bri1-9. Taken together, our results uncover a plant specific component of a plant ERAD pathway and also suggest its likely biochemical function. PMID- 26371325 TI - Erosion in southern Tibet shut down at ~10 Ma due to enhanced rock uplift within the Himalaya. AB - Exhumation of the southern Tibetan plateau margin reflects interplay between surface and lithospheric dynamics within the Himalaya-Tibet orogen. We report thermochronometric data from a 1.2-km elevation transect within granitoids of the eastern Lhasa terrane, southern Tibet, which indicate rapid exhumation exceeding 1 km/Ma from 17-16 to 12-11 Ma followed by very slow exhumation to the present. We hypothesize that these changes in exhumation occurred in response to changes in the loci and rate of rock uplift and the resulting southward shift of the main topographic and drainage divides from within the Lhasa terrane to their current positions within the Himalaya. At ~17 Ma, steep erosive drainage networks would have flowed across the Himalaya and greater amounts of moisture would have advected into the Lhasa terrane to drive large-scale erosional exhumation. As convergence thickened and widened the Himalaya, the orographic barrier to precipitation in southern Tibet terrane would have strengthened. Previously documented midcrustal duplexing around 10 Ma generated a zone of high rock uplift within the Himalaya. We use numerical simulations as a conceptual tool to highlight how a zone of high rock uplift could have defeated transverse drainage networks, resulting in substantial drainage reorganization. When combined with a strengthening orographic barrier to precipitation, this drainage reorganization would have driven the sharp reduction in exhumation rate we observe in southern Tibet. PMID- 26371324 TI - Activation of cyclic GMP-AMP synthase by self-DNA causes autoimmune diseases. AB - TREX1 is an exonuclease that digests DNA in the cytoplasm. Loss-of-function mutations of TREX1 are linked to Aicardi-Goutieres Syndrome (AGS) and systemic lupus erythematosus (SLE) in humans. Trex1(-/-) mice exhibit autoimmune and inflammatory phenotypes that are associated with elevated expression of interferon (IFN)-induced genes (ISGs). Cyclic GMP-AMP (cGAMP) synthase (cGAS) is a cytosolic DNA sensor that activates the IFN pathway. Upon binding to DNA, cGAS is activated to catalyze the synthesis of cGAMP, which functions as a second messenger that binds and activates the adaptor protein STING to induce IFNs and other cytokines. Here we show that genetic ablation of cGas in Trex1(-/-) mice eliminated all detectable pathological and molecular phenotypes, including ISG induction, autoantibody production, aberrant T-cell activation, and lethality. Even deletion of just one allele of cGas largely rescued the phenotypes of Trex1( /-) mice. Similarly, deletion of cGas in mice lacking DNaseII, a lysosomal enzyme that digests DNA, rescued the lethal autoimmune phenotypes of the DNaseII(-/-) mice. Through quantitative mass spectrometry, we found that cGAMP accumulated in mouse tissues deficient in Trex1 or DNaseII and that this accumulation was dependent on cGAS. These results demonstrate that cGAS activation causes the autoimmune diseases in Trex1(-/-) and DNaseII(-/-) mice and suggest that inhibition of cGAS may lead to prevention and treatment of some human autoimmune diseases caused by self-DNA. PMID- 26371326 TI - Effects of pre-encapsulated and pro-encapsulated Enterococcus faecalis on growth performance, blood characteristics, and cecal microflora in broiler chickens. AB - The effects of microencapsulation of Enterococcus faecalis on the growth performance, antioxidant activity, immune function, and cecal microbiota in broilers were investigated. Broilers (1-day-old) were assigned randomly as follows: 5 treatments, 5 replicate pens per treatment, and 20 broilers per pen. Treatments included (1) a basal diet (CON), (2) CON + Aureomycin (1 g/kg of diet) (ANT), (3) CON + free non-encapsulated probiotics (1 * 10(9) cfu/kg of diet) (FREE), (4) CON + pro-encapsulated probiotics (1 * 10(9) cfu/kg of diet) (PRO), and (5) CON + pre-encapsulated probiotics (1 * 10(9) cfu/kg of diet) (PRE). Feedings included starter (1 to 21 d) and grower (21 to 42 d) phases. In the starter phase, the ANT and the PRE groups had greater (P < 0.05) ADG than the CON groups, and the feed conversion ratio (FCR) for these 2 groups was decreased (P < 0.05). In the finisher phase, the PRE and PRO groups had greater (P < 0.05) ADG than the CON group and their FCR was decreased significantly (P < 0.05). During the entire feeding period, only the PRE group showed greater (P < 0.05) ADG and lower (P < 0.05) FCR. On day 21, only birds in the PRE group had greater (P < 0.05) total antioxidant capacity and number of Lactobacillus than the CON group. On day 42, The PRE group showed greater (P < 0.05) superoxide dismutase than the CON group. Serum IgA and IgM concentrations were increased (P < 0.05) in the PRE group. Serum IL-6 in the PRE group was greater (P < 0.05) than in the other groups with the exception of ANT. At the phylum level, Firmicutes was enriched (P < 0.05) and Proteobacteria was depleted (P < 0.05) only in the PRE group. At the genus level, only the PRE diets increased (P < 0.05) the number of both Lactobacillus and Enterococcus. The results indicate that pre-encapsulation assists the efficient functioning of probiotics in broilers. PMID- 26371327 TI - Effects of exogenous proteases without or with carbohydrases on nutrient digestibility and disappearance of non-starch polysaccharides in broiler chickens. AB - The objective of the current study was to evaluate the effect of a subtilisin protease, without or with inclusion of carbohydrases, on digestibility and retention of energy and protein, as well as the solubilization and disappearance of non-starch polysaccharides (NSP) from corn-soybean meal based diets fed to broiler chickens. Two hundred eighty-eight Ross 308 male broiler chickens were used for the experiment. On d 14, the birds were weighed and allocated to 6 treatments and 8 replicates per treatment with 6 birds per replicate. Treatments were: 1) corn-soybean meal based control diet; 2) control diet plus supplemental protease at 5,000 (P5000) protease units (PU)/kg); 3) control plus 10,000 PU/kg protease (P10000); or control plus an enzyme combination containing xylanase, amylase, and protease (XAP) added to achieve protease activity of: 4) 2,500 PU/kg (XAP2500); 5) 5,000 PU/kg (XAP5000); or 6) 10,000 PU/kg (XAP10000). The enzymes in XAP were combined at fixed ratios of 10:1:25 of xylanase:amylase:protease. Data were analyzed by ANOVA and specific orthogonal contrasts between treatments were performed. Addition of xylanase and amylase increased (P < 0.05) the ileal digestibility of protein by 4.2% and 2.1% at XAP5000 and XAP10000, respectively (relative to P5000 and P10000, respectively), exhibiting a plateau after the XAP5000 dose. Increment (P < 0.05) in AME due to protease was evident, particularly in P10000. At the ileal level, XAP reduced (P < 0.05) the flow of insoluble xylose and arabinose, which indicates an increase in the solubilization of arabinoxylan polymers in the small intestine. Protease on its own reduced (P < 0.05) the flow of insoluble arabinose but did not affect the flow of insoluble xylose. XAP reduced (P < 0.05) the pre-cecal flow of insoluble and total glucose and galactose. It was concluded that whereas protease by itself improved nutrient utilization and increased solubilization of NSP components, at the lower dose, a combination of xylanase, amylase, and protease produced effects greater than those of protease alone. PMID- 26371328 TI - Reduction of microbial contamination on the surfaces of layer houses using slightly acidic electrolyzed water. AB - The objective of this study was to evaluate the effectiveness of slightly acidic electrolyzed water (SAEW) in reducing pathogens on pure cultures and on cotton fabric surfaces in the presence of organic matter and estimate its efficacy in comparison with povidone iodine solution for reducing pathogenic microorganisms on internal surfaces of layer houses. Pure cultures of E.coli, S.enteritidis, and S.aureus and cotton fabric surfaces inoculated with these strains were treated with SAEW in the presence of bovine serum albumin (BSA). In the absence of BSA, complete inactivation of all strains in pure cultures and on cotton fabric surfaces was observed after 2.5 and 5 min treatment with SAEW at 40 mg/L of available chlorine concentration (ACC), respectively. The bactericidal efficiency of SAEW increased with increasing ACC, but decreased with increasing BSA concentration. Then, the surfaces of the layer houses were sprayed with SAEW at 60, 80, and 100 mg/L of ACC and povidone iodine using the automated disinfection system at a rate of 110 mL/m(2), respectively. Samples from the floor, wall, feed trough, and egg conveyor belt surfaces were collected with sterile cotton swabs before and after spraying disinfection. Compared to tap water, SAEW and povidone iodine significantly reduced microbial populations on each surface of the layer houses. SAEW with 80 or 100 mg/L of ACC showed significantly higher efficacy than povidone iodine for total aerobic bacteria, staphylococci, coliforms, or yeasts and moulds on the floor and feed trough surfaces (P < 0.05). SAEW was more effective than povidone iodine at reducing total aerobic bacteria, coliforms, and yeasts and moulds on the wall surface. Additionally, SAEW had similar bactericidal activity with povidone iodine on the surface of the egg conveyor belt. Results suggest that SAEW exerts a higher or equivalent bactericidal efficiency for the surfaces compared to povidone iodine, and it may be used as an effective alternative for reducing microbial contamination on surfaces in layer houses. PMID- 26371329 TI - Virulence gene content in Escherichia coli isolates from poultry flocks with clinical signs of colibacillosis in Brazil. AB - Escherichia coli is a commensal bacterium of the bird's intestinal tract, but it can invade different tissues resulting in systemic symptoms (colibacillosis). This disease occurs only when the E. coli infecting strain presents virulence factors (encoded by specific genes) that enable the adhesion and proliferation in the host organism. Thus, it is important to differentiate pathogenic (APEC, avian pathogenic E. coli) and non-pathogenic or fecal (AFEC, avian fecal E. coli) isolates. Previous studies analyzed the occurrence of virulence factors in E. coli strains isolated from birds with colibacillosis, demonstrating a high frequency of the bacterial genes cvaC, iroN, iss, iutA, sitA, tsh, fyuA, irp-2, ompT and hlyF in pathogenic strains. The aim of the present study was to evaluate the occurrence and frequency of these virulence genes in E. coli isolated from poultry flocks in Brazil. A total of 138 isolates of E. coli was obtained from samples of different tissues and/or organs (spleen, liver, kidney, trachea, lungs, skin, ovary, oviduct, intestine, cloaca) and environmental swabs collected from chicken and turkey flocks suspected to have colibacillosis in farms from the main Brazilian producing regions. Total DNA was extracted and the 10 virulence genes were detected by traditional and/or real-time PCR. At least 11 samples of each gene were sequenced and compared to reference strains. All 10 virulence factors were detected in Brazilian E. coli isolates, with frequencies ranging from 39.9% (irp-2) to 68.8% (hlyF and sitA). Moreover, a high nucleotide similarity (over 99%) was observed between gene sequences of Brazilian isolates and reference strains. Seventy-nine isolates were defined as pathogenic (APEC) and 59 as fecal (AFEC) based on previously described criteria. In conclusion, the main virulence genes of the reference E. coli strains are also present in isolates associated with colibacillosis in Brazil. The analysis of this set of virulence factors can be used to differentiate between APEC and AFEC isolates in Brazil. PMID- 26371330 TI - Antimicrobial susceptibilities of Campylobacter jejuni and Campylobacter coli recovered from organic turkey farms in Germany. AB - The popularity of food produced from animals kept under an organic regimen has increased in recent years. In Germany, turkey meat consumption has increased. Despite several studies assessing the susceptibility of campylobacters to various antibiotics in poultry, no sufficient data exists regarding the antimicrobial resistance of campylobacters in organic-reared turkeys. This study provides information about antibiotic resistance in Campylobacter isolated from turkeys reared on organic farms in Germany. Ninety-six Campylobacter strains (41 C. jejuni and 55 C. coli) were isolated from different free-range turkey flocks. In vitro antimicrobial sensitivity testing was done using a broth microdilution test, and the presence of resistance genes to antibiotics (ciprofloxacin, tetracycline) was investigated. All Campylobacter isolates from organic turkeys (n = 96) were phenotypically sensitive to gentamicin, erythromycin, streptomycin, and chloramphenicol. In this study, the antibiotic susceptibilities of C. jejuni to ciprofloxacin, tetracycline, and naladixic acid were 56.0%, 51.3%, and 56.0%, respectively. In contrast, 44.0%, 73.0%, and 74.6% of C. coli isolates were resistant to tetracycline, ciprofloxacin, and nalidixic acid, respectively. Replacement of the Thr-86->Ile in the gyrA gene, and the presence of the tet(O) gene were the mainly identified resistance mechanisms against fluoroquinolones and tetracycline, respectively.These results also reinforce the need to develop strategies and implement specific control procedures to reduce the development of antimicrobial resistance. PMID- 26371331 TI - Individual non-essential amino acids fortification of a low-protein diet for broilers under the hot and humid tropical climate. AB - A study was conducted to investigate the effects of feeding low-protein diets fortified with individual non-essential amino acids (NEAA) on growth performance, serum metabolites (uric acid, UA; triglycerides, TG; total protein, TP; and albumin, Alb), organ weight, breast yield, and abdominal fat weight in broiler chicks raised under the hot and humid tropical climate. Eight isocaloric (3,017 kcal/kg) experimental diets were formulated and fed to male broiler chicks from d 1-21 as follows: 1) 22.2% crude protein (CP) (positive control; PC); 2) 16.2% CP + mixture essential amino acids (EAA) to meet or exceed the National Research Council (1994) recommendations (negative control; NC); 3) NC + glycine (Gly) to equal the total glycine + serine level in the PC; diets 4 through 7 were obtained by supplementing NC diet with individual glutamic acid, proline, alanine, or aspartic acid (Glu, Pro, Ala, or Asp, respectively); 8) NC + NEAA (Gly + Glu + Pro + Ala + Asp) to equal the total level of these NEAA in the PC. Fortifying NC diet with mixture NEAA resulted in a similar growth performance as PC. However, fortification of low-CP diet with individual NEAA failed to improve body weight (BW) (P < 0.0001), feed intake (FI) (P = 0.0001), and feed conversion ratio (FCR) (P = 0.0001). Serum uric acid (UA) was lower (P = 0.0356) in NC birds and NC diet supplemented with individual NEAA birds, whereas serum triglyceride (TG) (P = 0.007) and relative weight of abdominal fat (P = 0.001) were higher in these birds. In conclusion, no single NEAA fortification may compensate the depressed growth performance attributed to a low-CP diet. However, fortification with Gly may improve FCR. There is a possibility that broilers raised under the hot and humid climate require higher Gly fortification than the level used in this study. PMID- 26371332 TI - Effect of dietary creatine monohydrate supplementation on muscle lipid peroxidation and antioxidant capacity of transported broilers in summer. AB - This experiment was to evaluate the effect of dietary supplementation with creatine monohydrate (CMH) during the finishing period on the muscle lipid peroxidation and antioxidant capacity of broilers that experienced transport stress in summer. A total of 320 male Arbor Acres broilers (28 d in age) were randomly allotted to 3 dietary treatments including a basal control diet without additional CMH (160 birds), or with 600 (80 birds) or 1,200 mg/kg (80 birds) CMH for 14 d. On the morning of d 42, after an 8-h fast, the birds fed the basal diets were divided into 2 equal groups, and all birds in the 4 groups of 80 birds were transported according to the following protocols: 1) a 0.75-h transport of birds on basal diets (as a lower-stress control group), 2) a 3-h transport of birds on basal diets, 3) a 3-h transport of birds on 600 or 4) 1,200 mg/kg CMH supplementation diets. The results showed that the 3-h transport decreased the concentration of creatine (Cr) in both the pectoralis major (PM) and the tibialis anterior (TA) muscles, increased the concentration of phosphocreatine (PCr) and PCr/Cr ratio in PM muscle, and elevated the concentrations of thiobarbituric acid reactive substances and the activities of total superoxide dismutase and glutathione peroxidase in both the PM and TA muscles of birds (P < 0.05). In addition, transport also upregulated mRNA expression of avian uncoupling protein and heat shock protein 70 in both the PM and TA muscles, as well as avian peroxisome proliferator-activated receptor gamma coactivator-1alpha in the TA muscle (P < 0.05). Dietary supplementation with 1,200 mg/kg CMH increased the concentrations of Cr and PCr in PM muscle, and Cr in TA muscle than those in the 3-h transport group (P < 0.05). However, contrary to our hypothesis, dietary CMH did not alter the measured parameters in relation to muscle lipid peroxidation and antioxidant capacity affected by 3-h transport (P > 0.05). These results indicate that dietary CMH supplementation does not provide any significant protection via directly scavenging free radicals or increased antioxidant capacity of transported broilers. PMID- 26371334 TI - Reversible splenial lesion syndrome. PMID- 26371335 TI - Sixteenth International Symposium on Microdosimetry. PMID- 26371333 TI - Effect of a low-protein diet supplemented with keto-acids on autophagy and inflammation in 5/6 nephrectomized rats. AB - Ketoacids (KA) are known to preserve muscle mass among patients with chronic kidney disease (CKD) on a low-protein diet (LPD). The present study was to compare the effects of KA supplemented diet therapy in autophagy and inflammation in CKD rats' skeletal muscle. Rats with 5/6 nephrectomy were randomly divided into three groups and fed with either 11 g/kg/day protein [normal-protein diet (NPD)], 3 g/kg/day protein (LPD) or 3 g/kg/day protein which including 5% protein plus 1% KA (LPD + KA) for 24 weeks. Sham-operated rats with NPD intake were used as control. LPD could improve body weight, gastrocnemius muscle mass, as well as gastrocnemius muscle cross-sectional area, with the effect being more obvious in the LPD + KA group. The autophagy marker LC3 (microtubule-associated protein 1 light chain 3), p62, Parkin and PTEN induced putative kinase 1 (PINK1) were significantly attenuate in LPD + KA group than LPD group. LPD + KA group had the lower total mtDNA (mitochondiral DNA) and cytosol mtDNA, NACHT-PYD-containing protein 3 (NALP3) inflammasome than LPD group, but its reactive oxygen species (ROS), caspase-1 and apoptosis-associated speck-like protein containing a CARD (ASC) level was higher. Immunoblotting showed IL-1beta (interleukin-1-beta) was lower in LPD and LPD + KA group than the NPD group, but IL-18 showed no significant difference among control and CKD group; toll-like receptor signalling dependent IL-6 was higher in LPD + KA group than LPD group, but tumor necrosis factor-alpha (TNF-alpha) was not significantly changed between LPD + KA and LPD group. Systematic changes of the four cytokines were different from that of the tissue. Although LPD + KA could further ameliorate-activated autophagy than LPD, its effect on the activated inflammation state in CKD was not distinctly. Further study is still required to explore the method of ameliorating inflammation to provide new therapeutic approaches for CKD protein energy wasting (PEW). PMID- 26371336 TI - Optimism and the brain: trait optimism mediates the protective role of the orbitofrontal cortex gray matter volume against anxiety. AB - Converging evidence identifies trait optimism and the orbitofrontal cortex (OFC) as personality and brain factors influencing anxiety, but the nature of their relationships remains unclear. Here, the mechanisms underlying the protective role of trait optimism and of increased OFC volume against symptoms of anxiety were investigated in 61 healthy subjects, who completed measures of trait optimism and anxiety, and underwent structural scanning using magnetic resonance imaging. First, the OFC gray matter volume (GMV) was associated with increased optimism, which in turn was associated with reduced anxiety. Second, trait optimism mediated the relation between the left OFC volume and anxiety, thus demonstrating that increased GMV in this brain region protects against symptoms of anxiety through increased optimism. These results provide novel evidence about the brain-personality mechanisms protecting against anxiety symptoms in healthy functioning, and identify potential targets for preventive and therapeutic interventions aimed at reducing susceptibility and increasing resilience against emotional disturbances. PMID- 26371337 TI - The person within: memory codes for persons and traits using fMRI repetition suppression. AB - Neuroimaging studies on trait inference demonstrated that the ventral medial prefrontal cortex (mPFC) houses neural representations of memory codes for traits . In this study, we investigate the neural code not only of traits, but also of persons who exemplify these traits. We used repetition suppression, which is a rapid suppression of the neuroimaging signal upon repeated presentation of the same stimulus or core stimulus characteristics-in this case, the implied trait and person. Participants inferred familiar person's traits. At each trial, a critical (target) sentence described a behavior that implied a trait, and was preceded by a (prime) sentence that implied the same trait and portrayed the same person, the same trait but portrayed a different person or did not imply a trait and portrayed a different person. As predicted, we found partly overlapping repetition suppression areas in the ventral mPFC when persons and traits were repeated, indicating that not only traits but also familiar persons have a neural code in the ventral mPFC. We also found a negative correlation between activation when reading about a new person and participants' social network size, indicating that experience with larger social groups results in less recruitment of a person code. PMID- 26371338 TI - Prevalence and Specificity of the Abnormal Niacin Response: A Potential Endophenotype Marker in Schizophrenia. AB - The skin flush response to niacin is abnormally blunted among a subset of patients with schizophrenia (SZ), preferentially associates with SZ compared to other mental illnesses, occurs frequently in nonpsychotic members of SZ-affected families, appears heritable, and shows evidence of genetic association. The niacin response abnormality (NRA) may prove to be a useful SZ endophenotype. Using a laser Doppler flowmeter, we undertook this study to estimate the prevalence of NRA in SZ (n = 70), bipolar disorder (BP, n = 59), and healthy control (HC, n = 87) groups, and to estimate its specificity for the illness. From the dose-response curves, we calculated the concentration of methylnicotinate required to elicit a half-maximal blood flow (MBF) response (EC50 value) and MBF value for each subject. The median log10EC50 of the SZ was above the third quartile of log10EC50 of either the HC or BP groups, whereas the MBF was significantly lower in the SZ than in the HC or BP groups. With a definition of NRA of having both EC50 above the ninetieth percentile of the control samples and MBF response below the sixtieth percentile for the control range, the NRA predicted SZ with 31% sensitivity and 97% specificity. Moreover, the NRA was not influenced by age, gender, race, and cigarette smoking. In summary, the NRA may define a SZ subtype with a clinically significant phospholipid signaling defect. Understanding its molecular origins may shed light on the pathophysiology of SZ and suggest new tools for its early diagnosis and treatment. PMID- 26371340 TI - Regeneration of Full-Thickness Rotator Cuff Tendon Tear After Ultrasound-Guided Injection With Umbilical Cord Blood-Derived Mesenchymal Stem Cells in a Rabbit Model. AB - Rotator cuff tendon tear is one of the most common causes of chronic shoulder pain and disability. In this study, we investigated the therapeutic effects of ultrasound-guided human umbilical cord blood (UCB)-derived mesenchymal stem cell (MSC) injection to regenerate a full-thickness subscapularis tendon tear in a rabbit model by evaluating the gross morphology and histology of the injected tendon and motion analysis of the rabbit's activity. At 4 weeks after ultrasound guided UCB-derived MSC injection, 7 of the 10 full-thickness subscapularis tendon tears were only partial-thickness tears, and 3 remained full-thickness tendon tears. The tendon tear size and walking capacity at 4 weeks after UCB-derived MSC injection under ultrasound guidance were significantly improved compared with the same parameters immediately after tendon tear. UCB-derived MSC injection under ultrasound guidance without surgical repair or bioscaffold resulted in the partial healing of full-thickness rotator cuff tendon tears in a rabbit model. Histology revealed that UCB-derived MSCs induced regeneration of rotator cuff tendon tear and that the regenerated tissue was predominantly composed of type I collagens. In this study, ultrasound-guided injection of human UCB-derived MSCs contributed to regeneration of the full-thickness rotator cuff tendon tear without surgical repair. The results demonstrate the effectiveness of local injection of MSCs into the rotator cuff tendon. SIGNIFICANCE: The results of this study suggest that ultrasound-guided umbilical cord blood-derived mesenchymal stem cell injection may be a useful conservative treatment for full-thickness rotator cuff tendon tear repair. PMID- 26371339 TI - Age at First Episode Modulates Diagnosis-Related Structural Brain Abnormalities in Psychosis. AB - Brain volume and thickness abnormalities have been reported in first-episode psychosis (FEP). However, it is unclear if and how they are modulated by brain developmental stage (and, therefore, by age at FEP as a proxy). This is a multicenter cross-sectional case-control brain magnetic resonance imaging (MRI) study. Patients with FEP (n = 196), 65.3% males, with a wide age at FEP span (12 35 y), and healthy controls (HC) (n = 157), matched for age, sex, and handedness, were scanned at 6 sites. Gray matter volume and thickness measurements were generated for several brain regions using FreeSurfer software. The nonlinear relationship between age at scan (a proxy for age at FEP in patients) and volume and thickness measurements was explored in patients with schizophrenia spectrum disorders (SSD), affective psychoses (AFP), and HC. Earlier SSD cases (ie, FEP before 15-20 y) showed significant volume and thickness deficits in frontal lobe, volume deficits in temporal lobe, and volume enlargements in ventricular system and basal ganglia. First-episode AFP patients had smaller cingulate cortex volume and thicker temporal cortex only at early age at FEP (before 18-20 y). The AFP group also had age-constant (12-35-y age span) volume enlargements in the frontal and parietal lobe. Our study suggests that age at first episode modulates the structural brain abnormalities found in FEP patients in a nonlinear and diagnosis dependent manner. Future MRI studies should take these results into account when interpreting samples with different ages at onset and diagnosis. PMID- 26371341 TI - Pharmacological Elevation of Circulating Bioactive Phosphosphingolipids Enhances Myocardial Recovery After Acute Infarction. AB - Acute myocardial infarction (AMI) triggers mobilization of bone marrow (BM) derived stem/progenitor cells (BMSPCs) through poorly understood processes. Recently, we postulated a major role for bioactive lipids such as sphingosine-1 phosphate (S1P) in mobilization of BMSPCs into the peripheral blood (PB). We hypothesized that elevating S1P levels after AMI could augment BMSPC mobilization and enhance cardiac recovery after AMI. After AMI, elevating bioactive lipid levels was achieved by treating mice with the S1P lyase inhibitor tetrahydroxybutylimidazole (THI) for 3 days (starting at day 4 after AMI) to differentiate between stem cell mobilization and the known effects of S1P on myocardial ischemic pre- and postconditioning. Cardiac function was assessed using echocardiography, and myocardial scar size evolution was examined using cardiac magnetic resonance imaging. PB S1P and BMSPCs peaked at 5 days after AMI and returned to baseline levels within 10 days (p < .05 for 5 days vs. baseline). Elevated S1P paralleled a significant increase in circulating BMSPCs (p < .05 vs. controls). We observed a greater than twofold increase in plasma S1P and circulating BMSPCs after THI treatment. Mechanistically, enhanced BMSPC mobilization was associated with significant increases in angiogenesis, BM cell homing, cardiomyocytes, and c-Kit cell proliferation in THI-treated mice. Mice treated with THI demonstrated better recovery of cardiac functional parameters and a reduction in scar size. Pharmacological elevation of plasma bioactive lipids after AMI could contribute to BMSPC mobilization and could represent an attractive strategy for enhancing myocardial recovery and improving BMSC targeting. SIGNIFICANCE: Acute myocardial infarction (AMI) initiates innate immune and reparatory mechanisms through which bone marrow-derived stem/progenitor cells (BMSPCs) are mobilized toward the ischemic myocardium and contribute to myocardial regeneration. Although it is clear that the magnitude of BMSPC mobilization after AMI correlates with cardiac recovery, the molecular events driving BMSPC mobilization and homing are poorly understood. The present study confirms the role of bioactive lipids in BMSPC mobilization after AMI and proposes a new strategy that improves cardiac recovery. Inhibiting sphingosine-1 phosphate (S1P) lyase (SPL) allows for the augmentation of the plasma levels of S1P and stem cell mobilization. These findings demonstrate that early transient SPL inhibition after MI correlates with increased stem cell mobilization and their homing to the infarct border zones. Augmenting BMSPC mobilization correlated with the formation of new blood vessels and cardiomyocytes and c-Kit cell proliferation. These novel findings on the cellular level were associated with functional cardiac recovery, reduced adverse remodeling, and a decrease in scar size. Taken together, these data indicate that pharmacological elevation of bioactive lipid levels can be beneficial in the early phase after cardiac ischemic injury. These findings provide the first evidence that a carefully timed transient pharmacological upregulation of bioactive lipids after AMI could be therapeutic, because it results in significant cardiac structural and functional improvements. PMID- 26371343 TI - Generation of Self-Renewing Hepatoblasts From Human Embryonic Stem Cells by Chemical Approaches. AB - Somatic stem cells play crucial roles in organogenesis and tissue homeostasis and regeneration and may ultimately prove useful for cell therapy for a variety of degenerative diseases and injuries; however, isolation and expansion of most types of somatic stem cells from tissues are technically challenging. Human pluripotent stem cells are a renewable source for any adult cell types, including somatic stem cells. Generation of somatic stem cells from human pluripotent stem cells is a promising strategy to get these therapeutically valuable cells. Previously, we developed a chemically defined condition for mouse hepatoblast self-renewal through a reiterative screening strategy. In the present study, we efficiently generated hepatoblasts from human embryonic stem cells by a stepwise induction strategy. Importantly, these human embryonic stem cell-derived hepatoblasts can be captured and stably maintained using conditions previously established for mouse hepatoblast self-renewal, which includes basal media supplemented with insulin, transferrin, sodium selenite, epidermal growth factor, glycogen synthase kinase 3 inhibitor, transforming growth factor beta receptor inhibitor, lysophosphatidic acid, and sphingosine 1-phosphate. The cells can stably retain hepatoblast phenotypes during prolonged culture and can differentiate into mature hepatocytes through in vitro provision of hepatocyte lineage developmental cues. After being embedded into three-dimensional Matrigel, these cells efficiently formed bile duct-like structures resembling native bile duct tissues. These human embryonic stem cell-derived hepatoblasts would be useful as a renewable source for cell therapy of liver diseases. SIGNIFICANCE: Somatic stem cells have been proposed as promising candidates for cell-based therapy; however, isolation of somatic stem cells from adult tissues is usually invasive and technically challenging. In the present study, hepatoblasts from human embryonic stem cells were efficiently generated. These human hepatoblasts were then stably captured and maintained by a growth factor and small molecule cocktail, which included epidermal growth factor, glycogen synthase kinase 3 inhibitor, transforming growth factor beta receptor inhibitor, lysophosphatidic acid, and sphingosine 1-phosphate. These human embryonic stem cell-derived hepatoblasts would be useful as a renewable source for cell therapy of liver diseases. PMID- 26371342 TI - Functional Effects of a Tissue-Engineered Cardiac Patch From Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes in a Rat Infarct Model. AB - A tissue-engineered cardiac patch provides a method to deliver cardiomyoctes to the injured myocardium with high cell retention and large, controlled infarct coverage, enhancing the ability of cells to limit remodeling after infarction. The patch environment can also yield increased survival. In the present study, we sought to assess the efficacy of a cardiac patch made from human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to engraft and limit left ventricular (LV) remodeling acutely after infarction. Cardiac patches were created from hiPSC-CMs and human pericytes (PCs) entrapped in a fibrin gel and implanted acutely onto athymic rat hearts. hiPSC-CMs not only remained viable after in vivo culture, but also increased in number by as much as twofold, consistent with colocalization of human nuclear antigen, cardiac troponin T, and Ki-67 staining. CM+PC patches led to reduced infarct sizes compared with myocardial infarction-only controls at week 4, and CM+PC patch recipient hearts exhibited greater fractional shortening over all groups at both 1 and 4 weeks after transplantation. However, a decline occurred in fractional shortening for all groups over 4 weeks, and LV thinning was not mitigated. CM+PC patches became vascularized in vivo, and microvessels were more abundant in the host myocardium border zone, suggesting a paracrine mechanism for the improved cardiac function. PCs in a PC-only control patch did not survive 4 weeks in vivo. Our results indicate that cardiac patches containing hiPSC-CMs engraft onto acute infarcts, and the hiPSC-CMs survive, proliferate, and contribute to a reduction in infarct size and improvements in cardiac function. SIGNIFICANCE: In the present study, a cardiac patch was created from human induced pluripotent stem cell-derived cardiomyocytes and human pericytes entrapped in a fibrin gel, and it was transplanted onto infarcted rat myocardium. It was found that a patch that contained both cardiomyocytes and pericytes survived transplantation and resulted in improved cardiac function and a reduced infarct size compared with controls. PMID- 26371345 TI - Cognitive Efficacy (SIB) of 13.3 Versus 4.6 mg/24 h Rivastigmine Patch in Severe Alzheimer's Disease. AB - Severe Impairment Battery (SIB) data from the 24-week, randomized, double-blind ACTivities of daily living and cognitION (ACTION) study suggest that patients with severe Alzheimer's disease (AD) benefit from treatment with 13.3 versus 4.6 mg/24 h rivastigmine patch. The objective of this retrospective analysis was to further examine the cognitive efficacy of 13.3 versus 4.6 mg/24 h rivastigmine patch on individual SIB items, and SIB domains derived using factor analysis of these items. Change from baseline at Week 24 on 9 new factor-defined domains and individual items was calculated and compared using effect sizes (Cohen's d). Numerically less decline was observed with 13.3 versus 4.6 mg/24 h patch on all domains and the majority of individual items. Largest least squares mean treatment differences were observed on "visuospatial reasoning," "object naming," "recognition," "design copying," "social agency," "ideational praxis," and "comprehension" domains. These findings suggest 13.3 mg/24 h rivastigmine patch demonstrates broad cognitive efficacy across a range of SIB items and domains in patients with severe AD. PMID- 26371344 TI - Concise Review: Reprogramming, Behind the Scenes: Noncanonical Neural Stem Cell Signaling Pathways Reveal New, Unseen Regulators of Tissue Plasticity With Therapeutic Implications. AB - Interest is great in the new molecular concepts that explain, at the level of signal transduction, the process of reprogramming. Usually, transcription factors with developmental importance are used, but these approaches give limited information on the signaling networks involved, which could reveal new therapeutic opportunities. Recent findings involving reprogramming by genetic means and soluble factors with well-studied downstream signaling mechanisms, including signal transducer and activator of transcription 3 (STAT3) and hairy and enhancer of split 3 (Hes3), shed new light into the molecular mechanisms that might be involved. We examine the appropriateness of common culture systems and their ability to reveal unusual (noncanonical) signal transduction pathways that actually operate in vivo. We then discuss such novel pathways and their importance in various plastic cell types, culminating in their emerging roles in reprogramming mechanisms. We also discuss a number of reprogramming paradigms (mouse induced pluripotent stem cells, direct conversion to neural stem cells, and in vivo conversion of acinar cells to beta-like cells). Specifically for acinar-to-beta-cell reprogramming paradigms, we discuss the common view of the underlying mechanism (involving the Janus kinase-STAT pathway that leads to STAT3 tyrosine phosphorylation) and present alternative interpretations that implicate STAT3-serine phosphorylation alone or serine and tyrosine phosphorylation occurring in sequential order. The implications for drug design and therapy are important given that different phosphorylation sites on STAT3 intercept different signaling pathways. We introduce a new molecular perspective in the field of reprogramming with broad implications in basic, biotechnological, and translational research. SIGNIFICANCE: Reprogramming is a powerful approach to change cell identity, with implications in both basic and applied biology. Most efforts involve the forced expression of key transcription factors, but recently, success has been reported with manipulating signal transduction pathways that might intercept them. It is important to start connecting the function of the classic reprogramming genes to signaling pathways that also mediate reprogramming, unifying the sciences of signal transduction, stem cell biology, and epigenetics. Neural stem cell studies have revealed the operation of noncanonical signaling pathways that are now appreciated to also operate during reprogramming, offering new mechanistic explanations. PMID- 26371346 TI - DNMT3A rs1550117 Polymorphism is Associated With Late-Onset Alzheimer's Disease in a Chinese Population. AB - Alzheimer's disease (AD) is classified as a neurodegenerative disease, impacting on brain integrity and functioning, resulting in a progressive deterioration of cognitive capabilities. Epigenetic changes can be acquired over the life span and mediate environmental effects on gene expression. DNA-methyltransferase 3A (DNMT3A) plays an important role in the development of embryogenesis and the generation of aberrant methylation late-onset AD (LOAD). In this study, the rs1550117 polymorphism of DNMT3A was determined by polymerase chain reaction/restriction fragment length polymorphism and confirmed by sequencing. The results showed that AA genotype carriers had a 2.08-fold risk of developing LOAD in comparison with GG genotype carriers (odds ratio [OR] = 2.08, 95% confidence interval [CI]: 1.03-4.21,P= .038) and had a 2.05-fold risk for LOAD compared with GG+GA genotype carriers (OR = 2.05, 95% CI: 1.03-4.11,P= .038), indicating that the DNMT3A polymorphism supports a major role in the pathogenesis of LOAD and can be used as a stratification marker to predict an individual's susceptibility to LOAD. PMID- 26371348 TI - In Memoriam: Norman Sheppard. PMID- 26371347 TI - Computer-Aided Diagnosis System for Alzheimer's Disease Using Different Discrete Transform Techniques. AB - The different discrete transform techniques such as discrete cosine transform (DCT), discrete sine transform (DST), discrete wavelet transform (DWT), and mel scale frequency cepstral coefficients (MFCCs) are powerful feature extraction techniques. This article presents a proposed computer-aided diagnosis (CAD) system for extracting the most effective and significant features of Alzheimer's disease (AD) using these different discrete transform techniques and MFCC techniques. Linear support vector machine has been used as a classifier in this article. Experimental results conclude that the proposed CAD system using MFCC technique for AD recognition has a great improvement for the system performance with small number of significant extracted features, as compared with the CAD system based on DCT, DST, DWT, and the hybrid combination methods of the different transform techniques. PMID- 26371349 TI - In Memoriam: Hans A. Kretzschmar (1953-2014). PMID- 26371350 TI - Pseudo-Pelger-Huet anomaly in a patient on tacrolimus. PMID- 26371351 TI - Response: One Good Consult Begets Another,While Providing a Learning Experience. PMID- 26371352 TI - The NBNA: Together We Are Making a Difference. PMID- 26371353 TI - Family Presence in Adult Intensive Care Units. PMID- 26371355 TI - Breast Cancer Survival among African-Americans Living in the Midwest: Disparities and Recommendations to Decrease Mortality. AB - Socioeconomic status is highly correlated with breast cancer risk and outcomes. Omaha, Nebraska has the third highest African-American poverty rate of the 100 largest U.S. metropolitan areas. Access to healthcare is a major issue in this community. This study analyzed the state cancer registry data to establish a baseline for breast cancer survivorship among African-American women in Nebraska. Specifically, the study examined the 5-year survivorship difference between African-American women and White women and the factors associated with poor survival. It was found that the 5-year survival rate for African-American women was 43% compared to 75% for White women and that this disparity persisted after taking into consideration the staging differences. The multivariable analysis results indicated that in addition to being African-American, increasing age, late-stage diagnosis, and lower socioeconomic status were factors independently associated with reduced survival in this sample. Because of the younger age at diagnosis among African-American women, we recommend that health promotion and educational programs be directed toward younger women. A significantly larger proportion of African-Americans being diagnosed at a late stage also underscores the importance of education of women of all ages. Future research should examine quality and timing of treatment as well as comorbidity issues affecting African American women. PMID- 26371354 TI - The Impact of STORY on Depression and Fatigue in African-American Women with Breast Cancer. AB - The intervention Sisters Tell Others and Revive Yourself (STORY) is a teleconference intervention for African-American women with breast cancer that was studied with a randomized, non-blinded, intention-to-treat trial between 2006 and 2010 in the southeastern United States. This secondary data analysis research measured the impact of STORY on depression and fatigue in African-American women (N = 168) with breast cancer. The were no significant differences in depression or fatigue found between the intervention and control groups based on the Wilcoxon signed-rank test. Further research is needed to develop effective interventions aimed at decreasing depression and fatigue in African-American women with breast cancer. PMID- 26371356 TI - Sleep Quality, Pain and Self-Efficacy among Community-Dwelling Adults with Sickle Cell Disease. AB - The aim of this paper was to report the findings of a study examining relationships among sleep, pain, self-efficacy, and demographic attributes of community-dwelling adults with sickle cell disease (SCD). Sleep difficulty has been self-reported among adults with chronic pain. Past studies have demonstrated that chronic pain results in sleep difficulties and other complications that threaten effective functioning. Community-dwelling adults with SCD are living longer and need to be evaluated for sleep quality, pain, and self-efficacy. Little is known about whether adults with SCD-related pain have disturbances in sleep and self-efficacy, and if these disturbances are affected by age and/or gender. The purpose of this descriptive, correlational study was to examine the relationships among sleep, pain, self-efficacy, and demographic attributes among community-dwelling adults with SCD, and who use support services of state SCD Associations in the United States. For this secondary data analysis, the study was conducted from June, 2014 to December, 2014 and used a descriptive correlational design to analyze data from a primary study of a convenience sample of 90 subjects with SCD, who were 18 years of age and older. Linear regression was used to compute the relationship between dependent and independent variables. All measures were self-reported. It was found that gender did not significantly affect reports of sleep, pain, or self-efficacy. Self-efficacy accounted for direct relationships with sleep and inverse relationships with pain. Some individuals (16.7%) reported sleeping very well, however, the majority (83.3%) was not sleeping very well, and a greater number of individuals (93.3%) reported having some pain. Among adults with chronic SCD pain, self-efficacy is important in maintaining a stable quality of health. Future assessments, interventions, and research should include comprehensive sleep and pain evaluations, and measures to improve self-efficacy and sleep quality, as well as measures to decrease pain among community-dwelling adults with SCD. PMID- 26371357 TI - Muddling Through the Health System: Experiences of Three Groups of Black Women in Three Regions. AB - Health-care disparities are a well-documented concern among patients and providers who care for minority groups in the United States. In this study, focus groups were created from an original sample of 606 Black women representing three regions in the United States: the South, the Midwest, and the Virgin Islands. Composed of 10 randomly selected members each (n = 30), the focus groups provided insights into the nature of these disparities, with some suggestions for viable solutions. Participants voiced concerns regarding cultural taboos about discussing menopause, financial concerns, and negative experiences with healthcare leading to distrust in medical systems. The primary solution proposed was an increase in Black health-care professionals who would have increased rapport with, empathy for, and understanding of the concerns of Black women. PMID- 26371358 TI - A Postpartum Community-Based Weight Management Intervention Designed for Low Income Women: Feasibility and Initial Efficacy Testing. AB - Postpartum weight retention increases a woman's risk of entering subsequent pregnancies overweight or obese, and women who are overweight or obese in pregnancy face higher rates of complications for themselves and their infants. This study assessed the feasibility, acceptability, and initial efficacy of an intervention to prevent postpartum weight retention in predominantly low-income African-American women. A randomized control pilot study was conducted to test the effects of the intervention on weight, adiposity, health behaviors, and eating and exercise self-efficacy from baseline (Time 1) to study completion (Time 2). The women in the experimental group had significantly greater decreases in triceps skinfolds (p = 0.01) and subscapular skinfolds (p = 0.04) and had significantly greater nutrition knowledge (p =0.04) than the control group. The results indicate that women randomized to a postpartum weight management program significantly decreased adiposity, increased nutrition knowledge and action, and, in addition, the women found the intervention acceptable. PMID- 26371359 TI - Relationship of Intimate Partner Violence, HIV Risk Behaviors, and Powerlessness in African-American Women of Childbearing Age. AB - The purpose of this study was two-fold: (1) to examine the relationships among IPV, HIV risk behaviors, and the phenomenon of powerlessness in African-American women of childbearing age, and (2) to investigate the differences between type and severity of IPV, HIV risk behaviors, and powerlessness in African-American women of childbearing age who have and have not reported IPV This study used the theory of gender and power as a conceptual framework. A purposive sample of 130 African-American women ranging from 18 to 49 years of age from southeastern Louisiana was recruited from community clinics. A correlation/comparative analysis design was used in this study. Three self-report, self-administered surveys were used: The Abuse Assessment Screen-Revised, the HIV-Risk Screening Instrument-Revised, items from the subscale of powerlessness in the Trauma Related Belief Questionnaire, and a demographics questionnaire. Statistically significant relationships between IPV, HIV risk behaviors, and powerlessness were identified. Participants who had experienced emotional or physical abuse by their partners were identified to be at risk for HIV infection and a statistically significant relationship between IPV and powerlessness was identified. Participants who feared their partner or ex-partner reported higher degrees of powerlessness. Findings emphasized that for women who are identified as survivors of IPV, nurses need to screen for HIV infection, provide access to care and community resources, and teach skills for effective coping and risk-reduction decision-making. PMID- 26371360 TI - Patient-Centered Community Diabetes Education Program Improves Glycemic Control in African-American Patients with Poorly Controlled Type 2 Diabetes: Importance of Point of Care Metabolic Measurements. AB - African-Americans with type 2 diabetes (T2DM) have higher morbidity and mortality partly attributed to poor glucose control and lack of formal diabetes self management education and support (DSMES) programs compared to Whites. Therefore, the objective of this study was to compare the clinical and metabolic parameters during DSMES vs. standard care in African-Americans with T2DM attending primary care inner city clinics. We recruited 124 African-American patients with T2DM, randomized into Group 1-DSMES (n = 58) and Group 2-standard care group (n = 38) for 6 months. Body weight, blood pressure, random blood sugars and point-of-care (POC) hemoglobin A1C (A1C) and lipids/lipoproteins were measured at 0, 3, and 6 months. At 6 months, Group 1 had significant reduction in A1C (8.2 +/- 1.4% vs. 7.5 +/- 1.5%, p = 0.02) and random glucose (190.4 +/- 77.6 vs. 160.6 +/- 59.8 mg/dl, p = 0.03). However, there were no changes in body weight, blood pressure, or lipids/lipoprotein levels. We found no significant changes in the clinical/metabolic parameters in Group 2. We concluded that DSMES, supplemented with POC testing, was associated with significant improvements in glycemic control without changes in body weight, blood pressure, or lipids/lipoproteins. We recommend the inclusion of DSMES with POC testing in managing African-American patients with T2DM attending inner city primary care clinics. PMID- 26371361 TI - Urban Lit and Sexual Risk Behavior: A Survey of African-American Adolescent Girls. AB - Adolescents spend an inordinate amount of time engaged with media, which is highly sexualized. Sexualized material can be found in music, on television and the Internet, as well as in magazines and books. Adolescents engaged with media are often influenced by this sexualized content, leading them to engage in risky sexual behavior. Urban literature (urban lit) is extremely popular among African American female adolescents due to its portrayal of urban life and hip-hop culture. The purpose of this survey was to ascertain the extent to which African American adolescent females are reading urban literature and to document whether this genre of literature had an effect on their sexual risk behaviors. PMID- 26371362 TI - The effects of Panax notoginseng saponins on the cytokines and peritoneal function in rats with peritoneal fibrosis. AB - BACKGROUND: Due to the long-term and chronic exposure to the peritoneal dialysis fluid, patients could develop peritoneal fibrosis and ultrafiltration failure which compromises treatment efficacy and outcome, and fibrosis is the major cause of peritoneal dialysis (PD) withdraw among patients. METHODS: Twenty-one male WISTAR rats were randomly assigned to three groups, namely saline group, standard peritoneal dialysis fluid (PDF) group, and panax notoginseng saponins (PNS) group. Peritoneal fibrosis was induced by daily injection of PDF for 4 weeks. After execution, multiple histological techniques including HE and Masson's trichrome staining and transmission electron microscopy (TEM) were applied to observe the pathological changes and concentrations of multiple cytokines may involve in the process of fibrosis were determined by enzyme-linked immune sorbent assay (ELISA). Biochemistry parameters were determined by automated chemistry analyzer. RESULTS: PNS can significantly inhibit the expression of transforming growth factor beta (TGF-beta1), connective tissue growth factor (CTGF), and monocyte chemoattractant protein (MCP-1) in the peritoneum of rats. Furthermore, pathological damages, including extracellular matrix deposition, vascularization, and fibroblast, were ameliorated in PNS group when being compared with standard PDF group. Peritoneal functions were improved by regular PNS treatment with significantly elevated ultrafiltration. CONCLUSION: PNS is capable of improving peritoneal function in subjects with PDF exposure and can possibly applied in patients with PD after further verification. PMID- 26371364 TI - Valve-in-valve transcatheter aortic valve implantation overcoming hostile anatomy: Evolut R for the treatment of Mitroflow bioprosthesis dysfunction. AB - Redo surgery is regarded as the first-line treatment option for patients presenting with prosthetic valve degeneration. However, many patients have concomitant co-morbidities and this option is associated with significant risk. Transcatheter valve-in-valve implantation is an alternative strategy depending on the bioprosthetic valve that is being treated. The Sorin Mitroflow bioprosthetic aortic valve has been regarded as a contraindication to valve-in-valve treatment due to the high risk of coronary obstruction. We here present the case of a patient with small peripheral vasculature who underwent successful transfemoral valve-in-valve implantation and subsequently discuss the challenges and technical aspects that require consideration. PMID- 26371363 TI - Patients' Attitudes Towards Disclosure of Genetic Test Results to Family Members: The Impact of Patients' Sociodemographic Background and Counseling Experience. AB - Many factors predict the intention to disclose genetic information to relatives. The article examines the impact of patients' socio-demographic factors on their intention to disclose genetic testing results to their relatives. Data were collected in eight genetic clinics in Israel. Patients were requested to fill in a questionnaire after counseling. A convenience sample of 564 participants who visited these clinics was collected for a response rate of 85 %. Of them, 282 participants came for susceptibility testing for hereditary cancers (cancer group), and 282 for genetic screening tests (prenatal group). In the cancer group, being secular and having more years of education correlated positively with the intention to disclose test results to relatives. In the prenatal group, being married and female correlated positively with the intention to disclose. In the cancer group, being religious and with less years of education correlated positively with the view that the clinician should deliver the results to the family. In the prenatal group, being male and unmarried correlated positively with this belief. In both groups, being of young age correlated with the perception that genetic information is private. Varied sociodemographic factors affect the intention to inform family members. Thus, knowing the social background of patients will shed light on people's attitudes to genetic information and will help clinicians provide effective counseling in discussions with patients about the implications of test results for relatives. PMID- 26371365 TI - Population Dynamics of Anastrepha ludens (Loew) (Diptera: Tephritidae) on Citrus Areas in Southern Tamaulipas, Mexico. AB - An analysis of adult population fluctuation of Anastrepha ludens (Loew) was performed in southern Tamaulipas, Mexico from 2008 to 2011. The aim was to analyze population dynamics of A. ludens and its relationships with climatic factors in the citrus region of Llera, Tamaulipas, Mexico. Population densities were weekly examined to identify variation through the year and study period. Four periods were identified according to population size, amplitude, host availability and season of the year. The correlation between population density vs. rainfall and temperature (average, minimum and maximum) was determined by linear and multiple regression analyses. Simple linear regression analysis showed that population density with minimum temperature and rainfall was the most consistent correlation, whereas in multiple regression analysis, rainfall and maximum temperature showed more consistency. A seasonal association between the availability of commercial host, climatic variation, and population peaks of A. ludens was determined. This study may have practical implications for the design of specific control strategies, monitoring, and infestation prevention based on different phases of the pest through the year. This strategy, along with the area wide approach implemented by the Plant Protection Service may lead to an optimization of material, financial and human resources. PMID- 26371366 TI - Veterinary homeopathy: systematic review of medical conditions studied by randomised trials controlled by other than placebo. AB - BACKGROUND: No systematic review has previously been carried out on randomised controlled trials (RCTs) of veterinary homeopathy in which the control group was an intervention other than placebo (OTP). For eligible peer-reviewed RCTs, the objectives of this study were to assess the risk of bias (RoB) and to quantify the effect size of homeopathic intervention compared with an active comparator or with no treatment. METHODS: Our systematic review approach complied fully with the PRISMA 2009 Checklist. Cochrane methods were applied to assess RoB and to derive effect size using standard meta-analysis methods. Based on a thorough and systematic literature search, the following key attributes of the published research were distinguished: individualised homeopathy (n = 1 RCT)/non individualised homeopathy (n = 19); treatment (n = 14)/prophylaxis (n = 6); active controls (n = 18)/untreated controls (n = 2). The trials were highly diverse, representing 12 different medical conditions in 6 different species. RESULTS: No trial had sufficiently low RoB to be judged as reliable evidence: 16 of the 20 RCTs had high RoB; the remaining four had uncertain RoB in several domains of assessment. For three trials with uncertain RoB and without overt vested interest, it was inconclusive whether homeopathy combined with conventional intervention was more or was less effective than conventional intervention alone for modulation of immune response in calves, or in the prophylaxis of cattle tick or of diarrhoea in piglets. CONCLUSION: Due to the poor reliability of their data, OTP-controlled trials do not currently provide useful insight into the effectiveness of homeopathy in animals. PMID- 26371367 TI - Biomimetic approaches for cell implantation to the restoration of infarcted myocardium. AB - Compelling evidences accumulated over the years have proven stem cells as a promising source for regenerative medicine. However, the inadequacy with the design of delivery modalities has prolonged the research in realizing an ideal cell-based approach for the regeneration of infarcted myocardium. Currently, some modest improvements in cardiac function have been documented in clinical trials with stem cell treatments, although regenerating a fully functional myocardium remains a dream for cardiac surgeons. This review provides an overview on the significance of stem cell therapy, the current attempts to resolve the drawbacks with the cell implantation approach and the various stratagems adopted with electrospun hybrid nanofibers for implementation in myocardial regenerative therapy. PMID- 26371368 TI - Classification of hand eczema. AB - BACKGROUND: Classification of hand eczema (HE) is mandatory in epidemiological and clinical studies, and also important in clinical work. OBJECTIVES: The aim was to test a recently proposed classification system of HE in clinical practice in a prospective multicentre study. METHODS: Patients were recruited from nine different tertiary referral centres. All patients underwent examination by specialists in dermatology and were checked using relevant allergy testing. Patients were classified into one of the six diagnostic subgroups of HE: allergic contact dermatitis, irritant contact dermatitis, atopic HE, protein contact dermatitis/contact urticaria, hyperkeratotic endogenous eczema and vesicular endogenous eczema, respectively. An additional diagnosis was given if symptoms indicated that factors additional to the main diagnosis were of importance for the disease. RESULTS: Four hundred and twenty-seven patients were included, 379 (89%) of the patients could be classified directly into one of the six diagnostic subgroups, with irritant and allergic contact dermatitis comprising 249 patients (58%). For 32 (7%) more than one of the six diagnostic subgroups had been formulated as a main diagnosis, and 16 (4%) could not be classified. 38% had one additional diagnosis and 26% had two or more additional diagnoses. Eczema on feet was found in 30% of the patients, statistically significantly more frequently associated with hyperkeratotic and vesicular endogenous eczema. CONCLUSION: We find that the classification system investigated in the present study was useful, being able to give an appropriate main diagnosis for 89% of HE patients, and for another 7% when using two main diagnoses. The fact that more than half of the patients had one or more additional diagnoses illustrates that HE is a multifactorial disease. PMID- 26371369 TI - Relationship between calcium channel blocker class and mortality in dialysis. AB - BACKGROUND AND OBJECTIVE: The comparative effectiveness of dihydropyridine (DHP) and non-DHP calcium channel blockers (CCBs) in maintenance dialysis patients has not been well-studied. METHODS: A retrospective cohort of hypertensive patients initiating dialysis was created. New CCB initiators, defined as individual who had no evidence of CCB use in the first 90 days of dialysis but who were initiated by day 180, were followed from their first day of medication exposure until event or censoring; events consisted of all-cause mortality (ACM) and a combined endpoint of cardiovascular morbidity or mortality (CVMM). Cox proportional hazards models were used to determine adjusted hazard ratios (AHRs) comparing the effect of DHPs vs. non-DHPs. RESULTS: There were 2900 and 2704 new initiators of CCBs in the ACM and CVMM models, respectively. Adjusted for other factors, use of DHPs, compared to non-DHPs, was associated with an AHR of 0.77 (99% confidence intervals, 0.64 - 0.93, P = 0.0004) for ACM and 0.86 (0.72 - 1.02, P = 0.024) for CVMM. Results were similar when individuals who initiated therapy at any point after the cohort inception were included, with AHRs of 0.60 (0.53 - 0.69, P < 0.0001) and 0.77 (0.67 - 0.89, P < 0.0001) for ACM and CVMM, respectively. Further, elimination of individuals with chronic atrial fibrillation resulted in AHRs of 0.71 and 0.70 for ACM and CVVM, respectively. CONCLUSION: DHPs, as compared to non-DHPs, were associated with reduced hazard of death or cardiovascular morbidity and mortality; potential mechanisms of action require further study. PMID- 26371370 TI - Outcomes of Total Laparoscopic Hysterectomy Using a 5-mm Versus 10-mm Laparoscope: A Randomized Control Trial. AB - STUDY OBJECTIVE: To determine if the use of a 5-mm umbilical incision and laparoscope would result in a higher likelihood of earlier discharge from hospital after total laparoscopic hysterectomy (TLH) compared with a 10-mm umbilical incision and laparoscope. Secondary objectives of the study were to determine if the use of a 5-mm laparoscope would lead to a reduction in postoperative pain scores and a shorter operating time without an increase in complication rates. DESIGN: Prospective, randomized, double-blinded, clinical trial (Canadian Task Force classification I). SETTING: A tertiary care setting. PATIENTS: Seventy-eight patients scheduled for TLH were prospectively recruited. INTERVENTIONS: Women undergoing TLH were assigned to either a 5-mm umbilical port and laparoscope (5LH) or a 10-mm umbilical port and laparoscope (10LH). All patients underwent a standardized operative technique and anesthetic protocol. Patients and research assistants responsible for postoperative pain assessment were blinded to group. Analysis was by intention-to-treat. MEASUREMENTS AND MAIN RESULTS: The primary outcome measure was length of hospital stay. Secondary outcome measures were operating time, pain scores on postoperative days 1 and 7, and complication rates. There was no difference in length of hospital stay between the 2 arms. Compared with the 10LH group, the 5LH group had shorter operative times (32.6 vs 40 minutes; p = .01) and less postoperative pain on day 1 (2.5 vs 3.3; p = .03 for "pain with movement") and on day 7 (.92 vs 1.8; p = .002). Complication rates were similar between the 2 groups. CONCLUSION: TLH with a 5-mm laparoscope resulted in shorter operative times and less pain on postoperative days 1 and 7, compared with a 10-mm laparoscope, with similar length of stay and complications. PMID- 26371372 TI - Donor Killer Immunoglobulin-Like Receptor Profile Bx1 Imparts a Negative Effect and Centromeric B-Specific Gene Motifs Render a Positive Effect on Standard-Risk Acute Myeloid Leukemia/Myelodysplastic Syndrome Patient Survival after Unrelated Donor Hematopoietic Stem Cell Transplantation. AB - Donor killer immunoglobulin-like receptor (KIR) group B profiles (Bx) and homozygous of centromeric motif B (Cen-B/B) are the most preferable KIR gene content motifs for hematopoietic stem cell transplantation (HSCT). The risk of transplant from Bx1 donors and the benefit of the presence of Cen-B (regardless of number) were observed for standard-risk acute myeloid leukemia/myelodysplastic syndrome (AML/MDS) patients in this 4-year retrospective study. A total of 210 Chinese patients who underwent unrelated donor HSCT were investigated. Donor KIR profile Bx was associated with significantly improved overall survival (OS; P = .026) and relapse-free survival (RFS; P = .021) and reduced nonrelapse mortality (NRM; P = .017) in AML/MDS patients. A significantly lower survival rate was observed for transplants from Bx1 donors compared with Bx2, Bx3, and Bx4 donors for patients in first complete remission (n = 82; OS: P = .024; RFS: P = .021). Transplant from donors with Cen-B resulted in improved OS (HR = .256; 95% CI, .084 to .774; P = .016) and RFS (HR = .252; 95% CI, .084 to .758; P = .014) in AML/MDS patients at standard risk. However, this particular effect did not increase with a higher number of Cen-B motifs (cB/B versus cA/B; OS: P = .755; RFS: P = .768). No effect was observed on high-risk AML/MDS, acute lymphoblastic leukemia/non-Hodgkin lymphoma, and chronic myelogenous leukemia patients. Avoiding the selection of HSCT donors of KIR profile Bx1 is strongly advisable for standard-risk AML/MDS patients. The presence of the Cen-B motif rather than its number was more important in donor selection for the Chinese population. PMID- 26371373 TI - Effect of Cytomegalovirus Reactivation on Relapse after Allogeneic Hematopoietic Stem Cell Transplantation in Pediatric Acute Leukemia. AB - Recent studies have demonstrated the protective effect of cytomegalovirus (CMV) reactivation against relapse after allogeneic hematopoietic stem cell transplantation (HSCT) for adult myeloid malignancies. We assessed the association of CMV reactivation, defined as the development of CMV antigenemia (at least 1 pp65 antigen-positive cell per 5.0 * 10(4) WBCs) within 100 days after HSCT, with the risk of relapse in 143 patients with pediatric acute leukemia. The median age at HSCT was 7 years, and underlying diseases included acute lymphoblastic leukemia in 101 patients and acute myeloid leukemia in 42. The cumulative incidence of CMV reactivation at day 100 after HSCT was 45.4%. At a median follow-up of 88 months, patients with CMV reactivation had significantly lower 5-year cumulative incidence of relapse compared with patients without CMV reactivation. In a multivariate analysis, high-level CMV reactivation (>=10 pp65 antigen-positive cells) was an independent factor associated with reduced relapse. However, CMV reactivation was also associated with higher nonrelapse mortality (NRM), mostly caused by opportunistic infection after grades II to IV acute graft-versus-host disease (GVHD), which resulted in decreased probability of survival. High-level CMV reactivation was a risk factor for increased NRM and worse overall survival in multivariate analysis. Although CMV reactivation may reduce the risk of relapse after HSCT for pediatric acute leukemia, effective management of severe acute GVHD and better prophylaxis and treatment of opportunistic infections are required to reduce the incidence of NRM and improve survival. Further studies on pediatric HSCT that include a larger number of patients and more homogenous patient cohorts are desirable. PMID- 26371371 TI - Hematopoietic Cell Transplantation as Curative Therapy for Patients with Myelofibrosis: Long-Term Success in all Age Groups. AB - Myeloproliferative neoplasms (MPN) are chronic marrow disorders with variable prognoses. Most patients with polycythemia vera, essential thrombocythemia, or even primary myelofibrosis (PMF) are successfully treated with conservative strategies for years or even decades, and recent data suggest that even in patients with high-risk disease, in particular those with PMF, life expectancy can be extended by treatment with janus kinase (JAK2) inhibitors. However, none of those modalities are curative, and after marrow failure develops, the disease "accelerates," or transforms to acute leukemia, the only option able to effectively treat and, in fact, cure MPN is allogeneic hematopoietic cell transplantation (HCT). Outcome is superior if HCT is performed before leukemic transformation occurs. Several reports document survival in unmaintained remission beyond 10 years. The most recent analyses show reduced regimen-related mortality (less than 10% or even 5% at day 100) and progressively improved survival with both HLA-identical sibling and unrelated donors. The development of low/reduced-intensity conditioning regimens has contributed to the improved success rate and has allowed successful HCT in patients in their seventh and even eighth decade of life. We propose, therefore, that HCT should be offered to fit patients in these age groups and should be covered by their respective insurance carriers. PMID- 26371374 TI - The sequence Pro295-Thr311 of the hinge region of oestrogen receptor alpha is involved in ERK1/2 activation via GPR30 in leiomyoma cells. AB - The ERalpha (oestrogen receptor alpha)-derived peptide ERalpha17p activates rapid signalling events in breast carcinoma cells under steroid-deprived conditions. In the present study, we investigated its effects in ELT3 leiomyoma cells under similar conditions. We show that it activates ERK1/2 (extracellular-signal regulated kinase 1/2), the Galphai protein, the trans-activation of EGFR (epidermal growth factor receptor) and, finally, cell proliferation. It is partially internalized in cells and induces membrane translocation of beta arrestins. The activation of ERK1/2 is abolished by the GPR30 (G-protein-coupled receptor 30) antagonist G15 and GPR30 siRNA. When ERalpha is down-regulated by prolonged treatment with E2 (oestradiol) or specific ERalpha siRNA, the peptide response is blunted. Thus the simultaneous presence of GPR30 and ERalpha is required for the action of ERalpha17p. In addition, its PLM sequence, which interferes with the formation of the ERalpha-calmodulin complex, appears to be requisite for the phosphorylation of ERK1/2 and cell proliferation. Hence ERalpha17p is, to our knowledge, the first known peptide targeting ERalpha-GPR30 membrane cross-talk and the subsequent receptor-mediated biological effects. PMID- 26371376 TI - Global translation variations in host cells upon attack of lytic and sublytic Staphylococcus aureus alpha-haemolysin. AB - Genome-wide analyses of translation can provide major contributions in our understanding of the complex interplay between virulent factors and host cells. So far, the activation of host translational control mechanisms by bacterial toxins, owing to specific recruitment of mRNAs, RNA-binding proteins (RBPs) and ncRNAs (non-coding RNAs), are far from being understood. In the present study, we characterize for the first time the changes experienced by the translational control system of host cells in response to the well-known Staphylococcus aureus alpha-haemolysin (AHL) under both sublytic and lytic conditions. By comparing variations occurring in the cellular transcriptome and translatome, we give evidence that global gene expression is primarily rewired at the translational level, with the contribution of the RBP ELAVL1 (HuR) in the sublytic response. These results reveal the importance of translational control during host-pathogen interaction, opening new approaches for AHL-induced diseases. PMID- 26371375 TI - Solution NMR characterization of chemokine CXCL8/IL-8 monomer and dimer binding to glycosaminoglycans: structural plasticity mediates differential binding interactions. AB - Chemokine CXCL8/interleukin-8 (IL-8) plays a crucial role in directing neutrophils and oligodendrocytes to combat infection/injury and tumour cells in metastasis development. CXCL8 exists as monomers and dimers and interaction of both forms with glycosaminoglycans (GAGs) mediate these diverse cellular processes. However, very little is known regarding the structural basis underlying CXCL8-GAG interactions. There are conflicting reports on the affinities, geometry and whether the monomer or dimer is the high-affinity GAG ligand. To resolve these issues, we characterized the binding of a series of heparin-derived oligosaccharides [heparin disaccharide (dp2), heparin tetrasaccharide (dp4), heparin octasaccharide (dp8) and heparin 14-mer (dp14)] to the wild-type (WT) dimer and a designed monomer using solution NMR spectroscopy. The pattern and extent of binding-induced chemical shift perturbation (CSP) varied between dimer and monomer and between longer and shorter oligosaccharides. NMR-based structural models show that different interaction modes coexist and that the nature of interactions varied between monomer and dimer and oligosaccharide length. MD simulations indicate that the binding interface is structurally plastic and provided residue-specific details of the dynamic nature of the binding interface. Binding studies carried out under conditions at which WT CXCL8 exists as monomers and dimers provide unambiguous evidence that the dimer is the high-affinity GAG ligand. Together, our data indicate that a set of core residues function as the major recognition/binding site, a set of peripheral residues define the various binding geometries and that the structural plasticity of the binding interface allows multiplicity of binding interactions. We conclude that structural plasticity most probably regulates in vivo CXCL8 monomer/dimer GAG interactions and function. PMID- 26371377 TI - Single-Molecule Manipulation of the Duplex Formation and Dissociation at the G Quadruplex/i-Motif Site in the DNA Nanostructure. AB - We demonstrate the single-molecule operation and observation of the formation and resolution of double-stranded DNA (dsDNA) containing a G-quadruplex (GQ) forming and counterpart i-motif forming sequence in the DNA nanostructure. Sequential manipulation of DNA strands in the DNA frame was performed to prepare a topologically controlled GQ/i-motif dsDNA. Using strand displacement and the addition and removal of K(+), the topologically controlled GQ/i-motif dsDNA in the DNA frame was obtained in high yield. The dsDNA was resolved into the single stranded DNA, GQ, and i-motif by the addition of K(+) and operation in acidic conditions. The dissociation of the dsDNA under the GQ and i-motif formation condition was monitored by high-speed atomic force microscopy. The results indicate that the dsDNA containing the GQ- and i-motif sequence is effectively dissolved when the duplex is helically loosened in the DNA nanoscaffold. PMID- 26371379 TI - Risk perception of future cardiovascular disease in women diagnosed with a hypertensive disorder of pregnancy. AB - OBJECTIVE: The objective of this study is to evaluate a woman's risk perception for future cardiovascular disease (CVD) after being diagnosed with a hypertensive disorder of pregnancy. METHODS: A prospective cohort of women diagnosed with a hypertensive disorder of pregnancy (HDP) was studied. Each woman completed two surveys, one prior to hospital discharge and one 2 weeks later, designed to assess knowledge of and risk perception for future CVD based on their recent diagnosis of a HDP. Rates of postpartum depression were also assessed. RESULTS: Of the 146 subjects included, 28% were diagnosed with preeclampsia with severe features, 52.1% with preeclampsia with mild features, and 19.9% had chronic hypertension. Women with severe features and those delivering preterm were more likely to report a perception of increased risk of both recurrent HDP in a future pregnancy (p = 0.004 and 0.005, respectively) and hypertension later in life (p = 0.01 and 0.03, respectively). Women delivering preterm were more likely to report an accurate perception of increased risk of myocardial infarction and stroke compared to those delivering at term (p = 0.006 and 0.002, respectively). CONCLUSIONS: Disease severity and preterm delivery were associated with a higher likelihood of the perception of an increased risk for both recurrent HDP and hypertension in the future. Only preterm delivery was associated with a higher risk perception for stroke and myocardial infarction. Interventions targeted at improved health awareness in women diagnosed with HDP are warranted. PMID- 26371378 TI - Improving temporal cognition by enhancing motivation. AB - Increasing motivation can positively impact cognitive performance. Here we employed a cognitive timing task that allows us to detect changes in cognitive performance that are not influenced by general activity or arousal factors such as the speed or persistence of responding. This approach allowed us to manipulate motivation using three different methods; molecular/genetic, behavioral and pharmacological. Increased striatal D2Rs resulted in deficits in temporal discrimination. Switching off the transgene improved motivation in earlier studies, and here partially rescued the temporal discrimination deficit. To manipulate motivation behaviorally, we altered reward magnitude and found that increasing reward magnitude improved timing in control mice and partially rescued timing in the transgenic mice. Lastly, we manipulated motivation pharmacologically using a functionally selective 5-HT2C receptor ligand, SB242084, which we previously found to increase incentive motivation. SB242084 improved temporal discrimination in both control and transgenic mice. Thus, while there is a general intuitive belief that motivation can affect cognition, we here provide a direct demonstration that enhancing motivation, in a variety of ways, can be an effective strategy for enhancing temporal cognition. Understanding the interaction of motivation and cognition is of clinical significance since many psychiatric disorders are characterized by deficits in both domains. PMID- 26371380 TI - Quantitative Determination of Tenuazonic Acid in Pig and Broiler Chicken Plasma by LC-MS/MS and Its Comparative Toxicokinetics. AB - A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to quantitate tenuazonic acid (TeA) in pig and broiler chicken plasma was successfully developed and validated. Linear matrix-matched calibration curves ranged between 5 and 200 ng/mL. Correlation coefficients, goodness-of-fit coefficients, and within-day and between-day precision and accuracy fell well within the acceptance criteria. The limit of quantitation was 5.0 ng/mL in both pig and broiler chicken plasma. The LC-MS/MS method was applied in a comparative toxicokinetic study in both pigs and broiler chickens. TeA was completely bioavailable after oral administration in both animal species. However, absorption was deemed to be slower in broiler chickens (mean tmax 0.32 h in pigs vs 2.60 h in chickens). TeA was more slowly eliminated in broiler chickens (mean t1/2el 0.55 h in pigs vs 2.45 h in chickens after oral administration), mainly due to the significantly lower total body clearance (mean Cl 446.1 mL/h/kg in pigs vs 59.2 mL/h/kg in chickens after oral administration). Tissue residue studies and further research to elucidate the biotransformation and excretion processes of TeA in pigs, broiler chickens, and other animal species are imperative. PMID- 26371382 TI - Ankle and knee kinetics between strike patterns at common training speeds in competitive male runners. AB - The purpose of this study was to investigate the interaction of foot strike and common speeds on sagittal plane ankle and knee joint kinetics in competitive rear foot strike (RFS) runners when running with a RFS pattern and an imposed forefoot strike (FFS) pattern. Sixteen competitive habitual male RFS runners ran at two different speeds (i.e. 8 and 6 min mile(-1)) using their habitual RFS and an imposed FFS pattern. A repeated measures analysis of variance was used to assess a potential interaction between strike pattern and speed for selected ground reaction force (GRF) variables and, sagittal plane ankle and knee kinematic and kinetic variables. No foot strike and speed interaction was observed for any of the kinetic variables. Habitual RFS yielded a greater loading rate of the vertical GRF, peak ankle dorsiflexor moment, peak knee extensor moment, peak knee eccentric extensor power, peak dorsiflexion and sagittal plane knee range of motion compared to imposed FFS. Imposed FFS yielded greater maximum vertical GRF, peak ankle plantarflexor moment, peak ankle eccentric plantarflexor power and sagittal plane ankle ROM compared to habitual RFS. Consistent with previous literature, imposed FFS in habitual RFS reduces eccentric knee extensor and ankle dorsiflexor involvement but produce greater eccentric ankle plantarflexor action compared to RFS. These acute differences between strike patterns were independent of running speeds equivalent to typical easy and hard training runs in competitive male runners. Current findings along with previous literature suggest differences in lower extremity kinetics between habitual RFS and imposed FFS running are consistent among a variety of runner populations. PMID- 26371383 TI - The impact of interference on short-term memory for visual orientation. AB - Visual short-term memory serves as an efficient buffer for maintaining no longer directly accessible information. How robust are visual memories against interference? Memory for simple visual features has proven vulnerable to distractors containing conflicting information along the relevant stimulus dimension, leading to the idea that interacting feature-specific channels at an early stage of visual processing support memory for simple visual features. Here we showed that memory for a single randomly orientated grating was susceptible to interference from a to-be-ignored distractor grating presented midway through a 3 s delay period. Memory for the initially presented orientation became noisier when it differed from the distractor orientation, and response distributions were shifted toward the distractor orientation (by ~3 degrees ). Interestingly, when the distractor was rendered task-relevant by making it a second memory target, memory for both retained orientations showed reduced reliability as a function of increased orientation differences between them. However, the degree to which responses to the first grating shifted toward the orientation of the task relevant second grating was much reduced. Finally, using a dichoptic display, we demonstrated that these systematic biases caused by a consciously perceived distractor disappeared once the distractor was presented outside of participants' awareness. Together, our results show that visual short-term memory for orientation can be systematically biased by interfering information that is consciously perceived. PMID- 26371381 TI - Lipoprotein Particles in Adolescents and Young Women With PCOS Provide Insights Into Their Cardiovascular Risk. AB - CONTEXT: Adult women with polycystic ovarian syndrome (PCOS) have an increased risk for cardiovascular disease, but the evidence for this is controversial in adolescents and young women with PCOS. Measurement of low-density lipoprotein (LDL) particle number, measured by nuclear magnetic resonance spectroscopy is a novel technology to assess cardiovascular risk. OBJECTIVE: The objective of the study was to evaluate lipoprotein particle number and size in young women with PCOS and its relationship with insulin resistance and hyperandrogenism. DESIGN: This was a cross-sectional case control study. SETTING: The study was conducted at a clinical research center. PARTICIPANTS: Women with PCOS (n = 35) and normal controls (n = 20) participated in the study. INTERVENTIONS: Blood samples and anthropometric measures were obtained. MAIN OUTCOME MEASURES: LDL particle size and number were measured using nuclear magnetic resonance spectroscopy. A secondary outcome was to investigate the correlation of LDL particle number with high-sensitivity C-reactive protein, waist to hip ratio, hyperandrogenism, insulin resistance, and adiponectin. RESULTS: Women with PCOS had higher LDL particle number when compared with healthy controls (935 +/- 412 vs 735 +/- 264, P = .032); LDL particle number correlated strongly with high-sensitivity C reactive protein (r = 0.37, P = .006) and waist-to-hip (r = 0.57, P = .0003). The higher LDL particle number was driven mainly due to differences in the small LDL particle number (sLDLp), with PCOS patients having more sLDLp (348 +/- 305 vs 178 +/- 195, P = .015). The sLDLp correlated with the Matsuda index (r = -0.51, P = .0001), homeostasis model assessment index of insulin resistance (r = 0.41, P = .002), and adiponectin (r = -0.46, P = .0004) but not with T. CONCLUSION: Adolescent and young women with PCOS have an atherogenic lipoprotein profile suggestive of increased cardiovascular risk that appears to be driven by the degree of visceral adiposity and insulin resistance. PMID- 26371384 TI - T2MR and T2Candida: novel technology for the rapid diagnosis of candidemia and invasive candidiasis. AB - Candidemia and other forms of invasive candidiasis pose a significant diagnostic challenge. In order to provide the best treatment, it is important to accurately detect the fungal infection and identify the species. Historically, diagnosis of Candida infections depended upon three classical laboratory approaches: microbiologic, immunologic, histopathologic; and now includes new methods such as radiographic techniques, molecular, proteomic and biochemical methods. The T2Candida Panel has introduced a new class of infectious disease diagnostics that can rapidly detect and identify the causative pathogen of sepsis directly from a patient blood sample in a culture-independent manner. This test enables detection of Candida directly from the patient sample, a significant advance for the rapid and accurate diagnosis of invasive candidiasis. PMID- 26371385 TI - Impact of Serial B-Type Natriuretic Peptide Changes for Predicting Outcome in Asymptomatic Patients With Aortic Stenosis. AB - BACKGROUND: The aim of this study was to determine the impact on the outcome of serial B-type natriuretic peptide (BNP) changes during follow-up in asymptomatic patients with >= moderate aortic stenosis (AS) and preserved left ventricular ejection fraction. METHODS: We prospectively screened 69 patients who underwent comprehensive transthoracic echocardiography, BNP level measurement at baseline and after every 6 or 12 months. Annualized BNP changes were calculated as the difference between the last and baseline BNP measurements divided by the duration of follow-up. The primary endpoint was the occurrence of symptoms, aortic valve replacement, or cardiovascular death. RESULTS: During a follow-up of 30 +/- 19 months, 43 patients experienced a cardiac event. These patients were significantly older (73 +/- 9 vs 65 +/- 16 years; P = 0.010), had more often dyslipidemia (79% vs 42%; P = 0.038), more severe AS (peak velocity: 3.9 +/- 0.6 vs 3.5 +/- 0.6 m/s; P = 0.002), larger indexed left atrial area (10.2 +/- 2.5 vs 8.7 +/- 1.9 cm(2)/m(2); P = 0.006), and a higher increase in annualized BNP (+90 +/- 155 vs +7 +/- 49 pg/mL/y; P = 0.010). Patients with higher annualized BNP changes (> 20 pg/mL/y) had a significantly lower cardiac event-free survival (1 year: 63 +/- 8% vs 97 +/- 3%; 3 years: 31 +/- 8% vs 68 +/- 8%; P < 0.001). Using the multivariate Cox proportional hazards model, higher annualized BNP changes were significantly associated with increased risk of cardiac events (hazard ratio: 2.73, 95% confidence interval: 1.27-5.86; P = 0.010) after adjustment for age, dyslipidemia, and echocardiographic parameters. CONCLUSIONS: In asymptomatic patients with AS and preserved left ventricular ejection fraction, the use of serial BNP changes may help to anticipate development of class I indication for aortic valve replacement. PMID- 26371386 TI - The characterization of a base-width neutral step as the first step for balance recovery in moderate Parkinson's disease. AB - PURPOSE: The purpose of this study is to characterize the base-width neutral step (BNS) as the first step in a compensatory step response in persons with moderate Parkinson's disease (PD), and its effect on balance recovery. MATERIALS AND METHODS: Ten PD and 10 healthy controls (HCs) responded to a posterior waist pull. A BNS was defined if the first step was less than 50 mm. The length, height, duration and velocity of the BNS and its effect on balance recovery time and center of mass location at recovery were compared to the first step within other stepping strategies (single step (SS), multiple step (MS)). A linear mixed model was used to compare across strategies. RESULTS: Six of ten persons with PD compared to zero HC used a BNS. The BNS was shorter in length and duration compared to MS responses in HC, and shorter in duration compared to MS responses in PD. The BNS was slower in velocity compared to every other strategy. BNS use resulted in a longer recovery time compared to all strategies in HC and SS responses in PD, and trended toward a longer recovery time compared to MS responses in PD. CONCLUSIONS: The BNS as the first step in a MS response may be an unreported strategy for compensatory stepping in PD. This study suggests that the cost of utilizing the BNS may be a longer time for recovery, but further work is necessary to understand the progression of the BNS as PD severity increases. PMID- 26371388 TI - Evidence-Based Strategies to Reduce Postoperative Complications in Plastic Surgery. AB - Reconstructive plastic surgery is vital in assisting patients with reintegration into society after events such as tumor extirpation, trauma, or infection have left them with a deficit of normal tissue. Apart from performing a technically sound operation, the plastic surgeon must stack the odds in the favor of the patient by optimizing them before and after surgery. The surgeon must look beyond the wound, at the entire patient, and apply fundamental principles of patient optimization. This article reviews the evidence behind the principles of patient optimization that are commonly used in reconstructive surgery patients. PMID- 26371387 TI - [Ultrasound screening of abdominal aortic aneurysm: Lessons from Vesale 2013]. AB - Although aneurysm of the abdominal infra-renal aorta (AAA) meets criteria warranting B mode ultrasound screening, the advantages of mass screening versus selective targeted opportunistic screening remain a subject of debate. In France, the French Society of Vascular Medicine (SFMV) and the Health Authority (HAS) published recommendations for targeted opportunistic screening in 2006 and 2013 respectively. The SFMV held a mainstream communication day on November 21, 2013 in France involving participants from metropolitan France and overseas departments that led to a proposal for free AAA ultrasound screening: the Vesalius operation. Being a consumer operation, the selection criteria were limited to age (men and women between 60 and 75 years); the age limit was lowered to 50 years in case of direct family history of AAA. More than 7000 people (as many women as men) were screened in 83 centers with a 1.70% prevalence of AAA in the age-based target population (3.12% for men, 0.27% for women). The median diameter of detected AAA was 33 mm (range 20 to 74 mm). The prevalence of AAA was 1.7% in this population. Vesalius data are consistent with those of the literature both in terms of prevalence and for cardiovascular risk factors with the important role of smoking. Lessons from Vesalius to take into consideration are: screening is warranted in men 60 years and over, especially smokers, and in female smokers. Screening beyond 75 years should be discussed. Given the importance of screening, the SFMV set up a year of national screening for AAA (Vesalius operation 2014/2015) in order to increase public and physician awareness about AAA detection, therapeutic management, and monitoring. AAA is a serious, common, disease that kills 6000 people each year. The goal of screening is cost-effective reduction in the death toll. PMID- 26371389 TI - Clarification of the Definition of a "Biofilm". PMID- 26371390 TI - Comparison of Posteromedial Thigh Profunda Artery Perforator Flap and Anterolateral Thigh Perforator Flap for Head and Neck Reconstruction. AB - BACKGROUND: The anterolateral thigh perforator flap is a common workhorse flap for head and neck reconstruction. The authors present an alternative method using the posteromedial thigh profunda artery perforator flap and compare its characteristics, outcomes, donor-site morbidity, and donor-site cosmesis with those of the anterolateral thigh perforator flap. METHODS: Between May of 2013 and July of 2014, 41 patients undergoing head and neck reconstruction consisting of 18 posteromedial thigh profunda artery perforator flaps and 23 anterolateral thigh perforator flaps were included in this study. Thirty-eight of the patients were men, and the patient age ranged from 32 to 76 years (mean, 54.5 years). RESULTS: The success rate was 100 percent. The mean number of perforators was significantly higher in the profunda artery perforator flap group (2.0 versus 1.5). There was no significant difference in flap elevation time (66.3 minutes versus 60.7 minutes), pedicle length (9.8 cm versus 10 cm), flap area (166.1 cm versus 156.8 cm), flap width (7.7 cm versus 7.7 cm), reexploration rate, recipient-site complication rate, or donor-site complication rate. Based on patient self-assessment, the profunda artery perforator flap group had significantly better donor-site cosmesis than the anterolateral thigh perforator flap group (satisfaction rate, 100 percent versus 70 percent). CONCLUSIONS: The posteromedial thigh profunda artery perforator flap is a good alternative for head and neck reconstruction. It offers flap size, pedicle length, flap elevation time, and success rate comparable to those of the anterolateral thigh perforator flap. It has more perforators and better donor-site cosmesis than the anterolateral thigh perforator flap. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III. PMID- 26371391 TI - A Systematic Review and Meta-Analysis of Perforator-Pedicled Propeller Flaps in Lower Extremity Defects: Identification of Risk Factors for Complications. AB - BACKGROUND: Currently, increased interest in the perforator-pedicled propeller flap should not obscure the fact that it is, in reality, a complex procedure requiring experience and monitoring similar to free flaps. Through a meta analysis, the authors aimed to identify the risk factors of perforator-pedicled propeller flap failure in lower extremity defects. METHODS: The MEDLINE, PubMed Central, Embase, and Cochrane databases were searched from 1991 to May of 2014 for articles describing perforator-pedicled propeller flaps in the lower extremity. The study selection met the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Fixed-effects models were used. RESULTS: Forty articles complied with the inclusion criteria, representing 428 perforator pedicled propeller flaps. The most common cause was posttraumatic (55.2 percent). Most of the defects were at the distal third of the lower leg (45.6 percent). The arc of rotation was 180 degrees for 34.3 percent. Complications were found in 25.2 percent, including partial necrosis (10.2 percent) and complete necrosis (3.5 percent). Complete flap survival was found in 84.3 percent. The authors identified three significant risk factors: age older than 60 years (relative risk, 1.61; p = 0.03), diabetes (relative risk, 2.00; p = 0.02), and arteriopathy (relative risk, 3.12; p = 0.01). No significant results were found regarding smoking status other than a tendency (p = 0.06), acute cause (p = 0.59), posttraumatic cause (p = 0.97), distal third of the lower leg (p = 0.66), fascia inclusion (p = 0.70), and pedicle rotation greater than 120 degrees (p = 0.41). CONCLUSION: Age older than 60 years, diabetes, and arteriopathy are significant risk factors of perforator-pedicled propeller flap complications in the lower extremity. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, IV. PMID- 26371392 TI - Postoperative Prophylactic Antibiotic Use following Ventral Hernia Repair with Placement of Surgical Drains Reduces the Postoperative Surgical-Site Infection Rate. AB - BACKGROUND: To help prevent complications after incisional ventral hernia repair, traditional teaching has recommended using closed suction drains. However, some studies suggest that there is an increased infection risk with use of surgical drains, and it is uncertain whether use of extended postoperative prophylactic antibiotics while drains remain in place helps prevent surgical-site infections. Evidence guiding surgeons' clinical practice regarding antibiotic use following hernia repair is lacking. METHODS: The authors sought to determine whether the use of extended postoperative antibiotic prophylaxis beyond standard Surgical Care Improvement Project guidelines with closed-suction surgical drain placement in incisional ventral hernia repair reduces the incidence of postoperative surgical-site infections. A retrospective review of 234 patients who underwent an incisional ventral hernia repair from 2003 to 2013 at a single institution was performed. Demographic, preoperative, operative, and postoperative data were collected and analyzed. RESULTS: Extended postoperative prophylactic antibiotics significantly reduce the incidence of postoperative surgical-site infections (OR, 0.31; p < 0.01). The odds ratio, when stratified by Ventral Hernia Working Group Scale, was 0.63, 0.25, 0.30, and 0.13 (p < 0.001 by the Mantel-Haenszel combined test) for grades 1, 2, 3, and 4, respectively, but was not statistically significant for differences between hernia grades. However, as the hernia grade increased, the odds ratio tended to decrease, suggesting that extended prophylactic antibiotics may be more effective at decreasing the incidence of surgical-site infections at higher grades. CONCLUSION: Extended antibiotic prophylaxis reduces surgical site infection risk following complex ventral hernia repairs, and should be considered in all cases. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III. PMID- 26371394 TI - Exothermic Behavior of Thermal Decomposition of Sodium Percarbonate: Kinetic Deconvolution of Successive Endothermic and Exothermic Processes. AB - This study focused on the kinetic modeling of the thermal decomposition of sodium percarbonate (SPC, sodium carbonate-hydrogen peroxide (2/3)). The reaction is characterized by apparently different kinetic profiles of mass-loss and exothermic behavior as recorded by thermogravimetry and differential scanning calorimetry, respectively. This phenomenon results from a combination of different kinetic features of the reaction involving two overlapping mass-loss steps controlled by the physico-geometry of the reaction and successive endothermic and exothermic processes caused by the detachment and decomposition of H2O2(g). For kinetic modeling, the overall reaction was initially separated into endothermic and exothermic processes using kinetic deconvolution analysis. Then, both of the endothermic and exothermic processes were further separated into two reaction steps accounting for the physico-geometrically controlled reaction that occurs in two steps. Kinetic modeling through kinetic deconvolution analysis clearly illustrates the appearance of the net exothermic effect is the result of a slight delay of the exothermic process to the endothermic process in each physico-geometrically controlled reaction step. This demonstrates that kinetic modeling attempted in this study is useful for interpreting the exothermic behavior of solid-state reactions such as the oxidative decomposition of solids and thermal decomposition of oxidizing agent. PMID- 26371393 TI - Predictors of obstetric complications in women with heart disease. AB - OBJECTIVES: The objective of this study is to evaluate obstetric outcomes in women with heart disease and determine whether current multidisciplinary management approaches adversely affect the mother, the neonate, or both. Also to compare the accuracy of several risk scores (RS) including the modified World Health Organization classification (mWHO) and CARPREG to predict obstetric and neonatal complications and to study the addition value of Uteroplacental-Doppler flow (UDF) parameters to predict obstetric complications. METHODS: A prospective cohort study examined outcomes in women with heart disease (HD), the majority of whom had corrective surgery and delivered between January 2007 and March 2012. RESULTS: One hundred and seventy-four patients with 179 pregnancies were included in the study. Obstetric complications, including premature labor, arose in 87 patients (48.6%). Neonatal complications were observed in 11 cases (7%). On multivariate analysis, maternal heart disease was predictive of adverse perinatal events (46 cases, 25.7%) and mode of delivery (Thierry's spatula) of third- or fourth-degree perineal tears (six cases, 3.2%). mWHO classification predicted obstetric complications (p = 0.0001) better than the CARPREG study. Impaired UDF (uterine artery pulsatility index-20 weeks and umbilical artery pulsatility index 32 weeks in HD versus healthy women: 20w 1.12 versus 1.34, p = 0.005; 32w 0.87 versus 1.09, p = 0.008) was associated with adverse obstetric and offspring outcome in the group of HD pregnant women. CONCLUSIONS: Nearly 50% of pregnancies were associated with an adverse obstetric outcome, particularly IUGR. mWHO was better at predicting obstetric and neonatal complications that CARPREG in all categories. Furthermore, compromised UDF combined with mWHO improved the prediction of obstetric and offspring complications in this population. PMID- 26371395 TI - The Big Rust and the Red Queen: Long-Term Perspectives on Coffee Rust Research. AB - Since 2008, there has been a cluster of outbreaks of the coffee rust (Hemileia vastatrix) across the coffee-growing regions of the Americas, which have been collectively described as the Big Rust. These outbreaks have caused significant hardship to coffee producers and laborers. This essay situates the Big Rust in a broader historical context. Over the past two centuries, coffee farmers have had to deal with the "curse of the Red Queen"-the need to constantly innovate in the face of an increasing range of threats, which includes the rust. Over the 20th century, particularly after World War II, national governments and international organizations developed a network of national, regional, and international coffee research institutions. These public institutions played a vital role in helping coffee farmers manage the rust. Coffee farmers have pursued four major strategies for managing the rust: bioprospecting for resistant coffee plants, breeding resistant coffee plants, chemical control, and agroecological control. Currently, the main challenge for researchers is to develop rust control strategies that are both ecologically and economically viable for coffee farmers, in the context of a volatile, deregulated coffee industry and the emergent challenges of climate change. PMID- 26371396 TI - Total Synthesis of (-)-Exiguolide. AB - A concise total synthesis of (-)-exiguolide has been completed in an overall 2.8% yield over 20 steps in the longest linear path. The key strategies involve (1) Prins cyclization/homobromination of dienyl alcohol with the B ring-substituted aldehyde, prepared by Prins cyclization/bromination, to construct the A ring with excellent cis-Z stereochemical control and (2) an unusual side chain installation/macrocyclization strategy featuring Sonogashira cross-coupling followed by a ring-closing metathesis reaction to deliver the target. PMID- 26371398 TI - Toll-like receptor 4 gene Asp299Gly and Thr399Ile polymorphisms in type 2 diabetes mellitus: A meta-analysis of 15,059 subjects: Need for clarification of data in a recent meta-analysis. PMID- 26371397 TI - Vitamin-D deficiency impairs CD4+T-cell count recovery rate in HIV-positive adults on highly active antiretroviral therapy: A longitudinal study. AB - BACKGROUND & AIMS: We implemented a prospective study among human immunodeficiency virus (HIV)-positive adults to examine the association between vitamin-D deficiency (VDD) and insufficiency (VDI) vs sufficiency (VDS) and CD4+T cell improvement over 18 months of highly active antiretroviral therapy (HAART). METHODS: We used data from a randomized placebo-controlled micronutrient trial with 25-hydroxy vitamin-D (25(OH)D) measured at enrollment in 398 adults. CD4+T cell count was measured repeatedly at months 0, 3, 6, 12 and 18. Linear mixed models quantified the vitamin-D-related differences in CD4+T-cell count and associated 99% confidence intervals at baseline and respective follow-up intervals. RESULTS: At baseline 23%, 60% and 17% of participants were VDS, VDI and VDD, respectively. Absolute CD4+T- cell counts recovered during follow-up were persistently lower for baseline VDD and VDI relative to VDS participants. The greatest deficit in absolute CD4+T-cells recovered occurred in VDD vs VDS participants with estimates ranging from a minimum deficit of 26 cells/MUl (99% CI: -77, 26) to a maximum deficit of 65 cells/MUl (99% CI: -125, -5.5) during follow-up. This VDD-associated lower absolute CD4+T-cell gain was strongest among patients 35 years old or younger and among participants with a baseline body mass index of less than 25 kg/m(2). CONCLUSIONS: VDD is associated with lower absolute CD4+T-cell count recovery in HIV-positive patients on HAART. Vitamin-D supplementation may improve CD4+T-cell recovery during HAART. However, future intervention studies are needed to definitively evaluate the effectiveness of this vitamin as an adjunct therapy during HAART. PMID- 26371399 TI - When "together" means "too close": Agency motives and relationship functioning in coresident and living-apart-together couples. AB - The present research addresses the interplay between agency motives and objective dyadic closeness with regard to the functioning of intimate couple relationships. Applying a Person * Situation approach, we hypothesized (a) that partners' implicit and explicit agency motives predict their selection of dyadic living arrangements characterized by high or low objective closeness (coresidence or living-apart-together), (b) that agency motives have more negative effects on relationship functioning in coresident couples, (c) that agency motives predict agentic motivational states in coresident couples, and (d) that agentic states predict day-to-day changes in relationship satisfaction under conditions of high objective closeness. We found support for these between- and within-couple hypotheses in cross-sectional and prospective analyses of an age-heterogeneous sample of 548 heterosexual couples, and in a 2-week diary study with a subsample of 106 couples. Most notably, agentic motive dispositions and motivational states related to relationship functioning more negatively under conditions of high objective closeness. The overall positive effect of objective closeness on relationship functioning was diminished by strong agentic motivation. Perspectives for future research on agency motives in couple relationships are discussed. PMID- 26371400 TI - Individual differences in fundamental social motives. AB - Motivation has long been recognized as an important component of how people both differ from, and are similar to, each other. The current research applies the biologically grounded fundamental social motives framework, which assumes that human motivational systems are functionally shaped to manage the major costs and benefits of social life, to understand individual differences in social motives. Using the Fundamental Social Motives Inventory, we explore the relations among the different fundamental social motives of Self-Protection, Disease Avoidance, Affiliation, Status, Mate Seeking, Mate Retention, and Kin Care; the relationships of the fundamental social motives to other individual difference and personality measures including the Big Five personality traits; the extent to which fundamental social motives are linked to recent life experiences; and the extent to which life history variables (e.g., age, sex, childhood environment) predict individual differences in the fundamental social motives. Results suggest that the fundamental social motives are a powerful lens through which to examine individual differences: They are grounded in theory, have explanatory value beyond that of the Big Five personality traits, and vary meaningfully with a number of life history variables. A fundamental social motives approach provides a generative framework for considering the meaning and implications of individual differences in social motivation. (PsycINFO Database Record PMID- 26371401 TI - The experience matters more than you think: People value intrinsic incentives more inside than outside an activity. AB - We document a shift in the value assigned to intrinsic incentives: people value these incentives more inside an activity than outside the activity (i.e., during vs. before or after pursuit). For example, people care more about the level of interest of their present work task than of past or future work tasks. We document this shift across a variety of activities (exercising, visiting a museum, and lab tasks) and using various measures, including rated importance of intrinsic incentives inside and outside pursuit, actual and planned persistence on activities that offer these incentives, and regret when choosers outside pursuit forgo intrinsic incentives that pursuers later seek. This shift in valuation occurs because intrinsic incentives improve the experience during action pursuit, and therefore, this shift is unique to intrinsic incentives. Extrinsic incentives, by contrast, are valued similarly inside and outside pursuit. PMID- 26371402 TI - Quantitative Shear Wave Velocity Measurement on Acoustic Radiation Force Impulse Elastography for Differential Diagnosis between Benign and Malignant Thyroid Nodules: A Meta-analysis. AB - The aim of this study was to evaluate the diagnostic performance of quantitative shear wave velocity (SWV) measurement on acoustic radiation force impulse (ARFI) elastography for differentiation between benign and malignant thyroid nodules using meta-analysis. The databases of PubMed and the Web of Science were searched. Studies published in English on assessment of the sensitivity and specificity of ARFI elastography for the differentiation of thyroid nodules were collected. The quantitative measurement of ARFI elastography was evaluated by SWV (m/s). Meta-Disc Version 1.4 software was used to describe and calculate the sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and summary receiver operating characteristic curves. We analyzed a total of 13 studies, which included 1,854 thyroid nodules (including 1,339 benign nodules and 515 malignant nodules) from 1,641 patients. The summary sensitivity and specificity for differential diagnosis between benign and malignant thyroid nodules by SWV were 0.81 (95% confidence interval [CI]: 0.77 0.84) and 0.84 (95% CI: 0.81-0.86), respectively. The pooled positive and negative likelihood ratios were 5.21 (95% CI: 3.56-7.62) and 0.23 (95% CI: 0.17 0.32), respectively. The pooled diagnostic odds ratio was 27.53 (95% CI: 14.58 52.01), and the area under the summary receiver operating characteristic curve was 0.91 (Q* = 0.84). In conclusion, SWV measurement on ARFI elastography has high sensitivity and specificity for differential diagnosis between benign and malignant thyroid nodules and can be used in combination with conventional ultrasound. PMID- 26371403 TI - Intensity-Based Assessment of Microbubble-Enhanced Ultrasonography: Phase-Related Diagnostic Ability for Cellular Differentiation of Hepatocellular Carcinoma. AB - This prospective study aimed to elucidate the effect of phase-related quantitative parameters of contrast-enhanced ultrasound (CEUS) with perflubutane microbubble agent to assess the cellular differentiation of hepatocellular carcinoma (HCC). Intensity was analyzed in 94 lesions (19.4 +/- 4.9 mm, 86 patients), 47 well-differentiated HCCs (wHCCs) and 47 moderately-differentiated HCCs (mHCCs): I(e) (early phase) = I(te) (tumor) - I(le) (liver), I(p) (post vascular phase) = I(tp) (tumor) - I(lp) (liver), I(ep) = I(e) - I(p). The area under the receiver operating characteristic curve with the best cutoff value (I(e), 13.2, I(p), -4.5, I(ep), 21.3) for discriminating between wHCC and mHCC was 0.6922 for Ie, 0.7680 for Ip and 0.7925 for Iep, which indicated a significantly greater ability to differentiate between wHCC and mHCC compared with visual/qualitative assessment (early phase, 0.6170, p = 0.04; post-vascular phase, 0.6702, p = 0.01; both phases, 0.7021, p = 0.04). In conclusion, I(ep) was found to have the highest diagnostic ability, suggesting it is a promising parameter for the cellular differentiation of HCCs with CEUS. PMID- 26371405 TI - Sex and gender-related differences in alcohol use and its consequences: Contemporary knowledge and future research considerations. AB - AIMS: To review the contemporary evidence reflecting male/female differences in alcohol use and its consequences along with the biological (sex-related) and psycho-socio-cultural (gender-related) factors associated with those differences. METHODS: MEDLINE, PubMed, Web of Science, SCOPUS, PsycINFO, and CINAHL databases were searched for relevant publications, which were subsequently screened for the presence/absence of pre-specified criteria for high quality evidence. RESULTS: Compared to men, more women are lifetime abstainers, drink less, and are less likely to engage in problem drinking, develop alcohol-related disorders or alcohol withdrawal symptoms. However, women drinking excessively develop more medical problems. Biological (sex-related) factors, including differences in alcohol pharmacokinetics as well as its effect on brain function and the levels of sex hormones may contribute to some of those differences. In addition, differences in alcohol effects on behavior may also be driven by psycho-socio cultural (gender-related) factors. This is evident by variation in the magnitude of differences in alcohol use between countries, decreasing difference in the rates of alcohol consumption in recent generations and other findings. Evidence indicates that both sex and gender-related factors are interacting with alcohol use in complex manner, which differentially impacts the risk for development of the behavioral or medical problems and alcohol use disorders in men and women. CONCLUSIONS: Discovery of the mechanisms underlying biological (sex-related) as well as psycho-socio-cultural (gender-related) differences in alcohol use and related disorders is needed for development of personalized recommendations for prevention and treatment of alcohol use disorders and related problems in men and women. PMID- 26371404 TI - Impact of an exercise intervention on methamphetamine use outcomes post residential treatment care. AB - BACKGROUND: We examined the efficacy of an 8-week exercise intervention on posttreatment methamphetamine (MA) use among MA-dependent individuals following residential treatment. METHODS: 135 individuals newly enrolled in treatment were randomly assigned to a structured 8-week exercise intervention or health education control group. Approximately 1 week after completion of the intervention, participants were discharged to the community. Interview data and urine samples were collected at 1-, 3-, and 6-months post-residential care. Of the sample, 54.8% were classified as higher severity users (using MA more than 18 days in the month before admission) and 45.2% as lower severity users (using MA for up to 18 days in the month before admission). Group differences in MA use outcomes were examined over the 3 timepoints using mixed-multivariate modeling. RESULTS: While fewer exercise participants returned to MA use compared to education participants at 1-, 3- and 6-months post-discharge, differences were not statistically significant. A significant interaction for self-reported MA use and MA urine drug test results by condition and MA severity was found: lower severity users in the exercise group reported using MA significantly fewer days at the three post-discharge timepoints than lower severity users in the education group. Lower severity users in the exercise group also had a lower percentage of positive urine results at the three timepoints than lower severity users in the education group. These relationships were not present in the comparison of the higher severity conditions. CONCLUSION: Results support the value of exercise as a treatment component for individuals using MA 18 or fewer days/month. PMID- 26371406 TI - Predicting microbial traits with phylogenies. AB - Phylogeny reflects genetic and phenotypic traits in Bacteria and Archaea. The phylogenetic conservatism of microbial traits has prompted the application of phylogeny-based algorithms to predict unknown trait values of extant taxa based on the traits of their evolutionary relatives to estimate, for instance, rRNA gene copy numbers, gene contents or tolerance to abiotic conditions. Unlike the 'macrobial' world, microbial ecologists face scenarios potentially compromising the accuracy of trait reconstruction methods, as, for example, extremely large phylogenies and limited information on the traits of interest. We review 990 bacterial and archaeal traits from the literature and support that phylogenetic trait conservatism is widespread through the tree of life, while revealing that it is generally weak for ecologically relevant phenotypic traits and high for genetically complex traits. We then perform a simulation exercise to assess the accuracy of phylogeny-based trait predictions in common scenarios faced by microbial ecologists. Our simulations show that ca. 60% of the variation in phylogeny-based trait predictions depends on the magnitude of the trait conservatism, the number of species in the tree, the proportion of species with unknown trait values and the mean distance in the tree to the nearest neighbour with a known trait value. Results are similar for both binary and continuous traits. We discuss these results under the light of the reviewed traits and provide recommendations for the use of phylogeny-based trait predictions for microbial ecologists. PMID- 26371407 TI - On the concept of a psychrophile. PMID- 26371408 TI - Protein N-linked homocysteine is associated with recurrence of venous thromboembolism. AB - BACKGROUND: Recently, protein N-linked homocysteine (Hcy) has been measured in healthy subjects and patients with marked hyperhomocysteinemia. Since elevated total Hcy (tHcy) levels are associated with increased risk of venous thromboembolism (VTE), we aimed to investigate protein N-linked Hcy levels in patients with VTE. METHODS: We studied 200 consecutive patients with VTE (89 men, 111 women, aged from 17 to 83 years), including 57 subjects with a subsequent episode of VTE (recurrent VTE) during 24 months of follow-up. Protein N-linked Hcy was assayed using high-performance liquid chromatography with an on-column derivatization with o-phthaldialdehyde and fluorescence detection. RESULTS: The median protein N-linked Hcy was 1.404 MUM (interquartile range [IQR] 0.859 2.066), while the median tHcy (IQR) was 9.1 MUM (6.8-11.2). In the whole group protein N-linked Hcy correlated only with C-reactive protein (CRP; r = 0.44, p < 0.0001). In patients with recurrent VTE protein N-linked Hcy correlated with C reactive protein (r = 0.43, p < 0.0001), tHcy (r = 0.42, p = 0.001) and age (r = 0.32, p = 0.014), but not with thrombophilia, unprovoked VTE or the current anticoagulation. Hyperhomocysteinemia, defined as tHcy >= 15 MUM (n = 14.7%), was not associated with higher protein N-linked Hcy. Patients with recurrent VTE had higher levels of protein N-linked Hcy compared to those who experienced a single episode of VTE (1.553 MUM, 1.157-2.445 vs. 1.27 MUM, 0.826-1.884; p = 0.002). Multiple regression adjusted for potential confounders showed that the only independent predictor of protein N-linked Hcy in the upper quartile was CRP > 3mg/L (odds ratio 3.04, 95% confidence interval 2.12-4.36, p < 0.0001). CONCLUSION: Elevated protein N-linked Hcy concentrations, indicating enhanced protein homocysteinylation in vivo, characterize patients with recurrent VTE and this phenomenon is associated with enhanced inflammatory state. PMID- 26371409 TI - Incidence, determinants and the transient impact of cancer treatments on venous thromboembolism risk among lymphoma patients in Denmark. AB - BACKGROUND: Valid estimation of the incidence and risk factors for venous thromboembolism (VTE) among lymphoma patients has been limited by small studies focused on selected lymphoma subtypes and failure to account for death as a competing risk. Using a nationwide cohort of Danish lymphoma patients diagnosed from 2000 to 2010, we examined the incidence and risk factors for VTE and evaluated the transient impact of cancer treatments on VTE risk. METHODS: Medical databases contained cancer, comorbidity, treatment, and VTE information. We computed VTE incidence rates (IRs) per 1000 person-years and 1- and 2-year incidence accounting for competing risks. Using Cox proportional hazards models, we identified factors associated with VTE risk. In a nested self-controlled design, we evaluated the transient effect of chemotherapy, radiation, central venous catheter use and rituximab on VTE risk using logistic regression models and adjusted odds ratios (aORs). RESULTS: VTE IRs were >40/1000 person-years within 180 days post-diagnosis, decreasing to 8/1000 person-years in year two. VTE risk was 2.9% and 3.5% at 1 and 2 years, respectively. Lymphoma subtype, central nervous system involvement, and elevated lactate dehydrogenase were associated with VTE risk. Central venous catheter use increased the transient odds of VTE (aOR=6.7 (1.2, 28.1)). CONCLUSIONS: We report a lower VTE incidence among lymphoma patients compared with prior studies. Lymphoma aggressiveness was the main driver of baseline VTE risk, whereas central venous catheter use increased transient risks. These accurate estimates may improve the identification of lymphoma subgroups at highest VTE risk, for whom future targeted prevention interventions may be beneficial. PMID- 26371410 TI - Risk factors of infected sternal wounds versus sterile wound dehiscence. AB - BACKGROUND: Sterile sternal dehiscence (SSD) and sternal wound infections (SWIs) are two complications of median sternotomy with high rates of morbidity. Sternal wound complications also carry significant economic burden, almost tripling patients' hospital costs and are considered a nonreimbursable "never event" for Medicare. Historically, SDD and SWI have been recognized as discrete entities, but nonetheless continue to be categorized as a singular complication in literature. The purpose of this study was to determine specific patient demographic and perioperative predictors of SSD and SWI. MATERIALS AND METHODS: An institutional review board-approved, retrospective study of 8098 consecutive patients who underwent cardiac surgery at Columbia University Medical Center between January 2008 and December 2013 was conducted. Patients were categorized into three groups: no sternal wound complication, SSD, or SWI. Statistical analysis was performed using univariate and multivariate logistic regression analysis. RESULTS: Of 8098 patients, there were 73 patients (0.9%) with SSD and 40 (0.5%) with SWI who required plastic surgical consultation, debridement, and flap closure. In univariate analysis of SSD, positive predictors (i.e., "risk" factors) were age >42 years, prior surgery this admission, >=2 arterial conduits, internal mammary artery (IMA) grafting with or without previous IMA grafting, body mass index (BMI) >30 (obese), CHF, diabetes requiring medication, respiratory failure, and unplanned cardiac reoperation; negative predictors (i.e., "protective" factors) were no arterial conduits and extubation within 24 h. In univariate analysis of SWI, positive predictors were IMA grafting with or without previous IMA grafting, postoperative hematocrit urgent/emergent surgical priority, BMI >30 (obese), cardiac ejection fraction <40%, and respiratory failure; negative predictors were no arterial conduits and elective surgical priority. In multivariate regression, BMI >30, diabetes requiring medication, and respiratory failure were determined to be significant positive predictors of SSD, and IMA grafting with or without prior IMA grafting and respiratory failure were significant positive predictors for SWI; no significant negative predictors were identified. CONCLUSIONS: This study found that SSD and SWI have many common significant predictors consistent with findings that increased BMI, use of IMA grafts, poor cardiac reserve, and postoperative respiratory failure confer increased risk of sternal wound complications. Additionally, this study also found that there were predictors unique to each entity supporting that SSD and SWI may be related but are not a singular entity. Recognition and prevention of significant positive and negative predictors of SSD and SWI may be valuable in preoperative counseling, operative planning, and postoperative management. Although sternal wound complications can be successfully managed by plastic surgical intervention, preventing the development of median sternotomy complications may curb costs incurred by both patients and health care systems. PMID- 26371411 TI - Reduced heart rate variability in schizophrenia and bipolar disorder compared to healthy controls. AB - OBJECTIVE: Despite current diagnostic systems distinguishing schizophrenia (SZ) and bipolar disorder (BD) as separate diseases, emerging evidence suggests they share a number of clinical and epidemiological features, such as increased cardiovascular disease (CVD) risk. It is not well understood if poor cardiac autonomic nervous system regulation, which can be indexed non-invasively by the calculation of heart rate variability (HRV), contributes to these common CVD risk factors in both diseases. METHOD: We calculated HRV in 47 patients with SZ, 33 patients with BD and 212 healthy controls. Measures of symptom severity were also collected from the patient groups. RESULTS: Heart rate variability was significantly reduced in both these disorders in comparison with the healthy participants; however, there were no HRV differences between disorders. Importantly, these reductions were independent of the medication, age or body mass index effects. There was also preliminary evidence that patients with reduced HRV had increased overall and negative psychosis symptom severity regardless of SZ or BD diagnosis. CONCLUSION: We suggest that HRV may provide a possible biomarker of CVD risk and symptom severity in severe mental illness. Thus, our results highlight the importance of cardiometabolic screening across SZ and bipolar spectrum disorders. PMID- 26371412 TI - Outcome in Men with a Screen-detected Abdominal Aortic Aneurysm Who are not Fit for Intervention. AB - OBJECTIVE/BACKGROUND: Abdominal aortic aneurysm (AAA) screening in Gloucestershire has been ongoing for 25 years. The aim of this study was to review the outcome of a cohort of men with a large (> 5.4 cm) screen-detected AAA who did not have early intervention for their AAA. METHODS: A prospectively maintained database was interrogated for a 10-year interval from 2001 to 2011. Men who did not have their large AAA repaired within 3 months of the diagnosis were identified. The reasons for initial nonintervention and subsequent outcomes were identified from a combination of hospital case notes and general practitioner records. RESULTS: Of 334 men referred, 59 (median age 71 years, range 62-83 years) did not have intervention within 3 months (initial nonintervention rate 17.6%). The reasons included placed back on surveillance after assessment (n = 34); immediately discharged (n = 12); required further investigations (n = 5); died before complete assessment (n = 3); and incomplete follow-up (n = 5). Sixteen men had delayed AAA repair with no perioperative mortality. Overall mortality in the study was 14/34 (nine from ruptured AAA, the rest from medical conditions). Two further men survived repair of a ruptured AAA. The overall rate of ruptured AAA was 11/59 (18.6%). CONCLUSION: Information from studies such as these can be used to help plan treatment of men with a large AAA and to compare performance of vascular units. PMID- 26371413 TI - Commentary on 'Stroke/Death Rates Following Carotid Artery Stenting and Carotid Endarterectomy in Contemporary Administrative Dataset Registries: A Systematic Review'. PMID- 26371414 TI - Aortic Arch Morphology and Aortic Length in Patients with Dissection, Traumatic, and Aneurysmal Disease. AB - OBJECTIVES: To assess aortic arch morphology and aortic length in patients with dissection, traumatic injury, and aneurysm undergoing TEVAR, and to identify characteristics specific to different pathologies. METHOD: This was a retrospective analysis of the aortic arch morphology and aortic length of dissection, traumatic injury, and aneurysmal patients. Computed tomography imaging was evaluated of 210 patients (49 dissection, 99 traumatic injury, 62 aneurysm) enrolled in three trials that received the conformable GORE TAG thoracic endoprosthesis. The mean age of trauma patients was 43 +/- 19.6 years, 57 +/- 11.7 years for dissection and 72 +/- 9.6 years for aneurysm patients. A standardized protocol was used to measure aortic arch diameter, length, and take off angle and clockface orientation of branch vessels. Differences in arch anatomy and length were assessed using ANOVA and independent t tests. RESULTS: Of the 210 arches evaluated, 22% had arch vessel common trunk configurations. The aortic diameter and the distance from the left main coronary (LMC) to the left common carotid (LCC) were greater in dissection patients than in trauma or aneurysm patients (p < .001). Aortic diameter in aneurysm patients was greater compared with trauma patients (p < .05). The distances from the branch vessels to the celiac artery (CA) were greater in dissection and aneurysm patients than in trauma patients (p < .001). The take-off angle of the innominate (I), LCCA, and left subclavian (LS) were greater, between 19% and 36%, in trauma patients than in dissection and aneurysm patients (p < .001). Clockface orientation of the arch vessels varies between pathologies. CONCLUSIONS: Arch anatomy has significant morphologic differences when comparing aortic pathologies. Describing these differences in a large sample of patients is beneficial for device designs and patient selection. PMID- 26371415 TI - Male Sex Associated with Increased Long-term Cardiovascular Mortality after Peripheral Vascular Surgery for Atherosclerosis Despite Optimal Medical Treatment. AB - BACKGROUND: The cardiovascular burden and consequences of peripheral atherosclerosis appear to differ between men and women. Data regarding long-term outcomes, including the impact of medical prophylactic treatment, are insufficient. This study examined long-term outcomes according to sex following primary vascular surgery, adjusted for multiple variables as well as recommended medical prophylaxis. METHODS: All Danish patients who underwent peripheral vascular surgery from January 2000 to December 2007 were stratified into five procedural groups: (a) aorto-iliac bypass or thromboendarterectomy, (b) femoro femoral crossover, (c) thromboendarterectomy of the femoral arteries, (d) infrainguinal bypass, or (e) axillo- uni-, and bifemoral bypass. Data were analyzed according to sex for differences in myocardial infarction, stroke, and death, individually and combined, after surgery. RESULTS: A total of 11,234 patients were included: 6,289 males and 4,945 females. The overall adjusted hazard ratio for male patients compared with female patients for death was 1.11 (95% CI 1.06-1.17), for MI was 1.16 (95% CI 1.04-1.29), for stroke was 0.99 (95% CI 0.89-1.11), and for any major adverse cardiovascular event was 1.10 (95% CI 1.05-1.16). CONCLUSIONS: These findings show that, despite indication, severity, and concomitant medical treatment of peripheral artery disease, men have a higher risk of mortality and adverse cardiovascular events following surgery for peripheral arterial disease. PMID- 26371416 TI - Chimney Grafts in Aortic Stent Grafting: Hazardous or Useful Technique? Systematic Review of Current Data. AB - BACKGROUND: The chimney graft (CG) technique was introduced to rescue accidentally covered aortic branches during aortic endovascular repair. It extends the sealing zone. There is concern about "gutter" type I endoleak (EL-I) and about the durability of CGs. The aim of the present report was to analyze the rapidly increasing existing data. METHODS: A search was performed (PRISMA criteria) for all studies of visceral and thoracic/arch chimney grafts. Technical and clinical details and outcome were assessed. RESULTS: The present review includes 831 patients who underwent EVAR/TEVAR (endovascular aneurysm repair/thoracic endovascular aneurysm repair) with one or more chimney, periscope, or sandwich grafts. For aortic visceral vessels 517 patients received 911 visceral CGs and 314 patients received 364 arch CGs. Most procedures (81% visceral and 69% arch CGs) were elective. Thirty day mortality was 4% for both groups. The rate of early EL-I was 13% (visceral CGs) and 11% (arch CGs). Most EL I were handled conservatively (observation: 70% for visceral CG and 45% for arch CG). Early CG patency was high (97-99%) and remained high during follow up (median 17 months). Late (after 30 days) EL-I was reported in nine visceral (2%) and 12 arch (4%) CG cases. Few other late complications were reported, but those losing a kidney at the initial repair seemed to have a high risk of requiring permanent hemodialysis. CONCLUSION: Increasing amounts of data support the benefit of visceral and arch chimney graft techniques. In particular, the low early mortality and complication rates and high long-term patency seem advantageous; however, the majority of cases have been treated electively, and there is a high risk of bias in all studies. Mid- to long-term data suggest few late complications, except in cases where one renal artery was sacrificed. The CG technique is valuable for complex urgent patients and needs further documentation for other patient groups. PMID- 26371417 TI - Risk Factors Associated with Symptomatic Pulmonary Embolism of Catheter Directed Thrombolysis for Lower Extremity Deep Venous Thrombosis. AB - OBJECTIVE: The aim was to study the risk factors associated with symptomatic pulmonary embolism (PE) in patients with deep venous thrombosis (DVT) in the lower limbs treated by catheter directed thrombolysis (CDT) without inferior vena cava filter (IVCF) placement. METHODS: A total 266 patients with acute/subacute ilio-femoral, ilio-femoropopliteal, and femoropopliteal thrombosis confirmed by computed tomography venography or ultrasound Doppler were studied. All patients were treated with CDT. CTPA (computed tomography pulmonary angiography) examination was performed in all patients before thrombolysis. Patients with clinically suspected symptomatic PE were confirmed by repeated CTPA after treatment. The major outcome of this study was the occurrence of symptomatic PE events during CDT. RESULTS: During CDT, the incidence of symptomatic PE events was 4.9% (13/266). Patients with silent PE had a higher risk of developing symptomatic PE (10/110, 9.1%) than those who had no prior PE (3/156, 1.9%); multivariate analysis confirmed this difference (OR 4.018, 95% CI 1.048-15.402). It was also found that patients with previous heart disease had a higher risk of developing symptomatic PE (11/90, 12.2%) than those with no prior heart disease (2/176, 1.1%). Multivariate analysis confirmed that previous heart disease increased the risk of developing symptomatic PE (OR 10.407, 95% CI 2.228-48.617). One patient who suffered from heart failure and silent PE before CDT died of symptomatic PE (1/13, 7.7%). CONCLUSION: The risk of developing symptomatic PE is most markedly increased in patients with previous silent PE and heart disease. Selective rather than routine IVCF placement is an appropriate approach. PMID- 26371418 TI - Social place as a location of potential core transmitters-implications for the targeted control of sexually transmitted disease transmission in urban areas. AB - PURPOSE: Places are an important determinant of risk for sexually transmitted infection (STI) acquisition and transmission. We sought to identify social places that are critical for targeted STI control activities. The objective of this study was to determine whether sex partner meeting places characterized by drug markets, sex markets, and separately, drug and/or sex markets were more likely to have potential core transmitters as compared with other sex partner meeting places in one urban setting. METHODS: In 2008-2009, heterosexual sex partner places or venues were identified in Baltimore, MD using a venue-based study approach. RESULTS: A total of 1334 participants aged 18 to 35 years were enrolled at 85 venues. In those participants, 39 potential core transmitters were identified and 31% of venues had at least one potential core transmitter. In final age-adjusted and gender-adjusted models, core transmitters were significantly more likely to be identified at drug markets (OR = 1.37; 95% CI = 1.23-1.53), sex markets (OR = 1.27; 95% CI = 1.14-1.41), and drug and/or sex markets (OR = 1.49; 95% CI = 1.32-1.68). CONCLUSIONS: This study identified key characteristics of venues, such as drug and sex market activity, that may be important in identifying places for the targeted control of STI transmission. PMID- 26371419 TI - A novel mutation in DNAJB6, p.(Phe91Leu), in childhood-onset LGMD1D with a severe phenotype. AB - To identify and characterize genetic mutation in a Korean family with limb-girdle muscular dystrophy 1 (LGMD1), we analyzed in the affected family members clinical features, DNAJB6 by Sanger sequencing, muscle structures by magnetic resonance imaging (MRI), and functional consequences of the identified mutation using a zebrafish model. The clinical phenotypes along with identification of a novel c.271T > C (p.(Phe91Leu)) mutation in DNAJB6 led to the diagnosis of LGMD1D in the affected family members. This mutation presents unique clinical and radiological features compared with other DNAJB6 mutants. All affected members examined showed reduced pulmonary function, and had nasal voice and dysphagia except the two members who were thirteen and twelve years of age at the time of examination. Muscle phenotypes developed between 8 and 11 years of age and were more severe as compared to previously reported LGMD1D patients with mutant DNAJB6. Patients' MRI scans exhibited early involvement of the lateral head of gastrocnemius, in contrast to its late involvement in reported LGMD1D cases. Functional study using zebrafish embryos demonstrated that p.Phe91Leu elicits more severe muscle defects than the reported p.Phe93Leu and p.Pro96Arg mutations. We conclude that a novel p.(Phe91Leu) mutation in DNAJB6 is associated with severe childhood-onset LGMD1D. PMID- 26371420 TI - Synthesis of an oligonucleotide with a nicotinamide mononucleotide residue and its molecular recognition in DNA helices. AB - Nicotinamide adenine dinucleotide (NAD) is a pivotal redox cofactor of primary metabolism. Its redox reactivity is based on the nicotinamide mononucleotide (NMN) moiety. We investigated whether NMN(+) can engage in pairing interactions, when incorporated into an oligonucleotide. Here we describe the incorporation of NMN(+) at the 3'-terminus of an oligodeoxynucleotide via a phosphoramidate coupling in solution. The stability of duplexes and triplexes with the NMN(+) containing strand was measured in UV-melting curves. While the melting points of duplexes with different bases facing the nicotinamide were similar, triplex stabilities varied greatly between different base combinations, suggesting specific pairing. The most stable triplexes were found when a guanine and an adenine were facing the NMN(+) residue. Their triplex melting points were higher than those of the corresponding triplexes with a thymidine residue at the same position. These results show that NMN(+) residues can be recognized selectively in DNA helices and are thus compatible with the molecular recognition in nucleic acids. PMID- 26371422 TI - Editorial overview: Eukaryotic microbes: models and beyond. PMID- 26371421 TI - Molecular Signature of Response to Pazopanib Salvage Therapy for Urothelial Carcinoma. PMID- 26371423 TI - Re: Outcome in body-contouring surgery after massive weight loss: A prospective matched single-blind study. PMID- 26371424 TI - Half notching method for supermicrosurgical lambda-shaped lymphaticovenular anastomosis. PMID- 26371425 TI - A new methodology for inter- and intrafraction plan adaptation for the MR-linac. AB - The new era of hybrid MRI and linear accelerator machines, including the MR-linac currently being installed in the University Medical Center Utrecht (Utrecht, The Netherlands), will be able to provide the actual anatomy and real-time anatomy changes of the patient's target(s) and organ(s) at risk (OARs) during radiation delivery. In order to be able to take advantage of this input, a new generation of treatment planning systems is needed, that will allow plan adaptation to the latest anatomy state in an online regime. In this paper, we present a treatment planning algorithm for intensity-modulated radiotherapy (IMRT), which is able to compensate for patient anatomy changes. The system consists of an iterative sequencing loop open to anatomy updates and an inter- and intrafraction adaptation scheme that enables convergence to the ideal dose distribution without the need of a final segment weight optimization (SWO). The ability of the system to take into account organ motion and adapt the plan to the latest anatomy state is illustrated using artificial baseline shifts created for three different kidney cases. Firstly, for two kidney cases of different target volumes, we show that the system can account for intrafraction motion, delivering the intended dose to the target with minimal dose deposition to the surroundings compared to conventional plans. Secondly, for a third kidney case we show that our algorithm combined with the interfraction scheme can be used to deliver the prescribed dose while adapting to the changing anatomy during multi-fraction treatments without performing a final SWO. PMID- 26371427 TI - Clinicopathologic Characteristics of Microsatellite Instable Gastric Carcinomas Revisited: Urgent Need for Standardization. AB - Microsatellite instable gastric cancer (MSI-GC) is a specific molecular subtype of GC. We studied the phenotypes, genotypes, and clinicopathologic characteristics of MSI-GC in a white GC cohort and compared our findings with an extended literature review. The study cohort consisted of 482 patients. Specimens were available from 452 cases and were used for immunostaining (MLH1, PMS2, MSH2, MSH6) and molecular biological analyses (BAT-25, BAT-26, NR-21, NR-24, NR-27; Epstein-Barr virus in situ hybridization). Thirty-four (7.5%) GCs were MSI. Loss of MLH1 and/or PMS2 was found in 30 (88%) MSI-GC, 3 (9%) showed loss of MSH2 and/or MSH6. One (3%) MSI-GC was identified only by molecular biological testing. A single case was heterogeneous and contained microsatellite-stable and instable tumor areas. Twenty-one (62%) MSI-GCs showed unusual histologic features. MSI-GC was not found in diffuse-type or Epstein-Barr virus-positive GC. MSI-GC was significantly more prevalent in elderly patients, distal stomach, and was associated with a significantly lower number of lymph node metastases and a significantly better overall and tumor-specific survival. MSI-GC constitutes a small but relevant subgroup of GC with distinct clinicopathologic characteristics. Our literature review illustrates the shortcomings of missing standardized testing algorithms with prevalences of MSI-GC ranging from 0% to 44.5%. Future studies should test the hypothesis that patients with MSI-GCs may not need adjuvant/perioperative chemotherapy. However, this will require a standardized, quality-controlled diagnostic algorithm of MSI for GC. PMID- 26371428 TI - Association Between Phosphorylated Histone H3 and Oncotype DX Recurrence Scores in Breast Cancer. AB - We investigate the association between phosphorylated histone H3 (PhH3) and Oncotype DX recurrence score (RS). All invasive breast carcinoma with RS results from our city between 2007 and 2010 (n=47) were reviewed. Whole-tumor sections were stained for PhH3. Mitotic and PhH3 counts were performed and clinical charts reviewed. PhH3 correlated well with RS (r=0.69, P<0.001). Other correlations were: PhH3 versus mitotic count (r=0.87, P<0.001), PhH3 versus mitotic score (r=0.71, P<0.001), PhH3 versus modified Bloom-Richardson-Elston (MBR) grade (r=0.65, P<0.001), RS versus mitotic count (r=0.62, P<0.001), RS versus mitotic score (r=0.44, P=0.002), and RS versus MBR grade (r=0.49, P=0.001). Significant correlation between PhH3 and RS remained after controlling for mitotic count (r=0.39, P=0.007), mitotic score (r=0.60, P<0.001), MBR grade (r=0.56, P<0.001), and all 3 (r=0.37, P=0.014) by partial correlation. Two patients died of metastasis at 12 and 38 months after diagnosis. One had intermediate RS, and 1 high RS; both were in the top-third of PhH3 count. All other patients are alive and recurrence free. Correlation between PhH3 and RS was statistically significant in our cohort, and remained significant after controlling for traditional measures of proliferation. Given that RS has an established strong relationship with prognosis and therapy responsiveness, PhH3 may thus also be an important prognostic/predictive marker in breast cancer. PMID- 26371429 TI - Is Low Positive JAK2 V617F Mutation Test Result Clinically Significant?: Multi Institutional Study. AB - OBJECTIVES: Acquired somatic mutation Janus kinase 2 (JAK2) V617F is associated with various myeloproliferative neoplasms (MPN). Allele-specific real-time polymerase chain reaction has been widely adopted to detect mutation; however, the utility of low positive results is not well understood. The aim of this study is to investigate the clinical significance of low positivity of JAK2 V617F. MATERIALS AND METHODS: Retrospective analysis was performed for JAK2 V617F mutation tests performed using JAK2 MutaQuant kit (Ipsogen) in molecular laboratories at 2 major academic medical centers between 2010 and 2012. Cases with low positive JAK2 V617F, defined as 0.2% to 5% mutant allele, were documented. Chart review was performed for the clinical correlation. RESULTS: A total of 1697 JAK2 V617F tests was performed. Forty-five cases (2.65%) yielded a low JAK2 V617F positivity (average 1.45%), the majority of which (n=26, 62%) had <1%. Eight cases had a history of MPN. The remaining cases were related to reactive conditions without a clonal disease. Our data indicate that a low positivity of JAK2 V617F can be seen in MPN as well as reactive conditions. CONCLUSIONS: An interpretation of JAK2 V617F status should not be performed simply following some arbitrary cutoff. Any low positivity of JAK2 V617F should be reported and a correlation with clinical information is warranted for proper interpretation. PMID- 26371430 TI - Clinicopathologic and Immunohistochemical Characterization of Dedifferentiated Endometrioid Adenocarcinoma. AB - Dedifferentiated endometrioid adenocarcinoma (DEAC) of the uterus or ovary is characterized by the coexistence of low-grade endometrioid adenocarcinoma and an undifferentiated carcinoma (UC) with solid sheets of medium-sized monotonous epithelial cells. This admixed carcinoma has not been widely recognized, because the solid areas of UC have usually been misdiagnosed as a solid form of FIGO grade 3 endometrioid adenocarcinoma. These tumors have been shown to be clinically aggressive; therefore, accurate diagnosis is necessary for proper patient management. We reviewed our experience with DEACs and compared them with grade 3 endometrioid carcinomas regarding their clinicopathologic, morphologic, and immunohistochemical features. Our results indicate that DEACs are clinically aggressive tumors presented at advanced stages with vascular invasions in 73% and lymph node metastases in 46%. Thirty-eight percent of cases also showed distal metastases. Clinical follow-up data revealed that all patients had either recurrent or metastatic diseases within 3 years of diagnosis, except 1 patient who remained disease free for 3 years after diagnosis. Morphologically, UC components of DEACs were composed of diffuse sheets/solid nests of medium-sized epithelial cells with scant to moderate cytoplasm, uniform vesicular nuclei, and inconspicuous nucleoli. Although UC components of DEACs are variably positive for cytokeratin, EMA, and ER, they are mostly negative for PAX8, except 1 case. Instead, well-differentiated components of DEACs and solid grade 3 endometrioid carcinoma retained all these markers. Our results indicate that DEACs exhibit significantly different clinicopathologic features from grade 3 endometrioid adenocarcinoma, and a combination of immunohistochemical stains can be helpful to differentiate them from each other. PMID- 26371431 TI - Evaluation of PAX8 Expression in Brain Tissue and Related Neoplasms. AB - Undifferentiated brain tumors represent a diagnostic challenge, particularly in small biopsies, with regards to their primary versus metastatic origin. The latter may show overlapping morphologic features with primary high-grade brain tumors. In recent years several new antibodies have entered the realm of daily pathology practice. PAX8 (mammalian paired box genes 1 to 9 protein encoding gene) is among these new markers and is recognized as a differentiating marker of the primary site in epithelial tumors outside of the central nervous system. A review of the literature shows lack of site-specific studies with regards to the expression of PAX8 in the central nervous system and its neoplasms. Using this marker we investigated its immunohistochemical expression in normal brain tissue and glial tumors. The immunostain was performed on tissue microarrays of 71 cores from 24 cases. We also performed PAX8 immunostain on sections from cerebellum, pons, periventricular ependymal layer, choroid plexus, pituitary, and meninges of 3 autopsy cases. Our results indicate lack of PAX8 expression by benign brain tissue. Only 1 glioblastoma core (1/9 cores) showed focal nuclear reactivity with the antibody. Our results indicate that presence of PAX8 immunoreactivity in an undifferentiated brain tumor lacking gliofibrillary acidic protein expression should prompt consideration of a metastatic tumor. PMID- 26371432 TI - Identification of Human Papillomavirus Infection in Cancer Tissue by Targeted Next-generation Sequencing. AB - Human papillomaviruses (HPV) are oncogenic DNA viruses implicated in squamous cell carcinomas of several anatomic sites, as well as endocervical adenocarcinomas. Identification of HPV is an actionable finding in some carcinomas, potentially influencing tumor classification, prognosis, and management. We incorporated capture probes for oncogenic HPV strains 16 and 18 into a broader next-generation sequencing (NGS) panel designed to identify actionable mutations in solid malignancies. A total of 21 head and neck, genitourinary, and gynecologic squamous cell carcinomas and endocervical adenocarcinomas were sequenced as part of the UNCSeq project. Using p16 immunohistochemical results as the gold standard, we set a cutoff for proportion of aligned HPV reads that maximized performance of our NGS assay (92% sensitive, 100% specific for HPV). These results suggest that sequencing of oncogenic pathogens can be incorporated into targeted NGS panels, extending the clinical utility of genomic assays. PMID- 26371433 TI - Enhanced Expression of Hedgehog Pathway Proteins in Oral Epithelial Dysplasia. AB - The aim of this study was to characterize the profile of the proteins involved in the Hedgehog signaling pathway to aid in the understanding of the pathogenesis of oral epithelial dysplasia (OED). The proteins SHH, PTCH1, HHIP, SUFU, GLI1, and cyclin D1 were evaluated by immunohistochemistry in 25 cases of OED, 4 of non neoplasic oral mucosa, 8 of inflammatory fibrous hyperplasia and 5 of hyperkeratosis. SHH proteins were predominant in OED cases. Although PTCH1 protein was observed in all cases, this molecule was more highly expressed in OED. The inhibitor protein SUFU was present in OED and HHIP protein was overexpressed in OED. GLI1 proteins were predominantly found in the nuclei of epithelial cells in OED. Basal and suprabasal cells in the epithelial lining were positive for cyclin D1 only in OED. In conclusion, comparative analysis of the proteins involved in the Hedgehog pathway suggests that enhanced expression of these proteins can play an important role in the biological behavior of OED. PMID- 26371434 TI - Diffuse Cytokeratin Positivity in an Intradural Paraganglioma of the Lumbar Vertebra: A Diagnostic Pitfall! PMID- 26371435 TI - Diagnosis of Metaplastic Breast Carcinoma: Keratin OSCAR Versus Other Cytokeratins. AB - Metaplastic breast carcinoma (MBC) is a heterogenous group of tumors that diverge from conventional glandular differentiation. The metaplastic component can be focal or may be present purely posing diagnostic challenges. Since MBC may show focal immunostaining or may even be negative for some cytokeratins (CK), different CKs are often needed to prove their epithelial origin. OSCAR is a relatively new broad-spectrum anti-CK antibody. Thirty MBC cases diagnosed at our institution were retrieved, including 7 spindle cell carcinomas. Representative slides were immunostained for CK-OSCAR, CK-AE1/AE3, CAM5.2, CK-903, and CK5/6. Nineteen spindle cell lesions were used as controls, including 6 malignant and 10 borderline phyllodes tumor, 1 inflammatory pseudotumor, 1 solitary fibrous tumor, and 1 nodular fasciitis case. All 30 cases (100%) of metaplastic carcinomas were positive for CK-OSCAR, compared with 27/30 (90%, P=0.076) for CK-AE1/AE3, 21/30 (70%, P<=0.01) for CK-903, 19/30 (63.3%, P<=0.01) for CAM5.2, and 15/30 (50%, P<=0.01) for CK5/6. All control cases were negative for CK-OSCAR. All 7 spindle cell carcinomas were also positive for CK-OSCAR (100%) compared with 6/7 (85.7%) for CK-AE1/AE3, 4/7 (57%) for CK-903, 3/7 (42.8%) for CAM5.2, and 2/7 (28.5%) for CK5/6. Our data show that CK-OSCAR is more sensitive than other individual CKs in diagnosing MBC. Coupled with high specificity, CK-OSCAR may potentially be used in lieu of a panel of CKs to identify the epithelial origin of these tumors, especially in spindle cell tumors. This is particularly useful in limited core biopsy specimens, to help guide treatment and simultaneously lower testing costs. PMID- 26371437 TI - Tuning the relaxation rates of dual-mode T(1)/T(2) nanoparticle contrast agents: a study into the ideal system. AB - Magnetic resonance imaging (MRI) is an excellent imaging modality. However the low sensitivity of the technique poses a challenge to achieving an accurate image of function at the molecular level. To overcome this, contrast agents are used; typically gadolinium based agents for T1 weighted imaging, or iron oxide based agents for T2 imaging. Traditionally, only one imaging mode is used per diagnosis although several physiological situations are known to interfere with the signal induced by the contrast agents in each individual imaging mode acquisition. Recently, the combination of both T1 and T2 imaging capabilities into a single platform has emerged as a tool to reduce uncertainties in MR image analysis. To date, contradicting reports on the effect on the contrast of the coupling of a T1 and T2 agent have hampered the application of these specialised probes. Herein, we present a systematic experimental study on a range of gadolinium-labelled magnetite nanoparticles envisioned to bring some light into the mechanism of interaction between T1 and T2 components, and advance towards the design of efficient (dual) T1 and T2 MRI probes. Unexpected behaviours observed in some of the constructs will be discussed. In this study, we demonstrate that the relaxivity of such multimodal probes can be rationally tuned to obtain unmatched potentials in MR imaging, exemplified by preparation of the magnetite-based nanoparticle with the highest T2 relaxivity described to date. PMID- 26371436 TI - Structure-Based Inhibitor Design for Evaluation of a CYP3A4 Pharmacophore Model. AB - Human cytochrome P450 3A4 (CYP3A4) is a key xenobiotic-metabolizing enzyme that oxidizes and clears the majority of drugs. CYP3A4 inhibition may lead to drug drug interactions, toxicity, and other adverse effects but, in some cases, could be beneficial and enhance therapeutic efficiency of coadministered pharmaceuticals that are metabolized by CYP3A4. On the basis of our investigations of analogs of ritonavir, a potent CYP3A4 inactivator and pharmacoenhancer, we have built a pharmacophore model for a CYP3A4-specific inhibitor. This study is the first attempt to test this model using a set of rationally designed compounds. The functional and structural data presented here agree well with the proposed pharmacophore. In particular, we confirmed the importance of a flexible backbone, the H-bond donor/acceptor moiety, and aromaticity of the side group analogous to Phe-2 of ritonavir and demonstrated the leading role of hydrophobic interactions at the sites adjacent to the heme and phenylalanine cluster in the ligand binding process. The X-ray structures of CYP3A4 bound to the rationally designed inhibitors provide deeper insights into the mechanism of the CYP3A4-ligand interaction. Most importantly, two of our compounds (15a and 15b) that are less complex than ritonavir have comparable submicromolar affinity and inhibitory potency for CYP3A4 and, thus, could serve as templates for synthesis of second generation inhibitors for further evaluation and optimization of the pharmacophore model. PMID- 26371438 TI - Systematic reviews: Separating fact from fiction. AB - The volume of scientific literature continues to expand and decision-makers are faced with increasingly unmanageable volumes of evidence to assess. Systematic reviews (SRs) are powerful tools that aim to provide comprehensive, transparent, reproducible and updateable summaries of evidence. SR methods were developed, and have been employed, in healthcare for more than two decades, and they are now widely used across a broad range of topics, including environmental management and social interventions in crime and justice, education, international development, and social welfare. Despite these successes and the increasing acceptance of SR methods as a 'gold standard' in evidence-informed policy and practice, misconceptions still remain regarding their applicability. The aim of this article is to separate fact from fiction, addressing twelve common misconceptions that can influence the decision as to whether a SR is the most appropriate method for evidence synthesis for a given topic. Through examples, we illustrate the flexibility of SR methods and demonstrate their suitability for addressing issues on environmental health and chemical risk assessment. PMID- 26371439 TI - Anatomic basis of the middle temporal artery periosteal rotational flap in otologic surgery. AB - OBJECTIVES/HYPOTHESIS: To describe the elements critical to successful middle temporal artery periosteal rotational flap harvest and utilization based on the anatomic features of the middle temporal artery. STUDY DESIGN: Description of anatomy based on cadaver dissection. METHODS: Seventy temporal fossa dissections were performed on 35 adult human cadavers. RESULTS: Sixty-nine of 70 dissections had an identifiable middle temporal artery muscular branch pedicle in the periosteum deep to the temporalis muscle. Pedicle length was at least 7 cm in 32 of 38 (84%) male cadavers and in 20 of 31 (65%) female cadavers (P = 0.054), whereas the average length required to reach the digastric ridge from the pedicle base to the digastric ridge in a mastoidectomy cavity was 5.2 cm. The pedicle sharply transitions from a posterior to a posterior-superior course 0.93 cm superior (range: 0.5-1.9 cm) and 0.04 cm posterior (range: 1.4 cm posterior-0.7 cm anterior) to the spine of Henle. Branching occurred in 26 of 69 pedicles (38%), and 20 of 31 (65%) branches were oriented posteriorly. If temporalis muscle fibers are not incorporated into the flap, the thickness is roughly three times that of a standard temporalis fascia graft. CONCLUSION: The muscular branch of the middle temporal artery is reliably identified in the periosteum deep to the posterior aspect of the temporalis muscle, and this vessel is sufficiently robust to provide axial blood supply to a rotational periosteal flap that has sufficient thickness and length to allow a variety of applications in otologic surgery. LEVEL OF EVIDENCE: NA. Laryngoscope, 126:1426-1432, 2016. PMID- 26371440 TI - Does Educational Level Predict Mortality After Myocardial Infarction Independently of Left Ventricular Function and Medical Treatment? PMID- 26371441 TI - The timing of deep brain stimulation for Parkinson disease in the UK from 1997 to 2012. AB - BACKGROUND AND PURPOSE: Deep brain stimulation (DBS) for Parkinson disease (PD) has traditionally been reserved for the late stages of the disease. There is evidence that DBS is also effective if applied earlier in the disease course. Changes in the frequency of DBS procedures in the UK over a 15-year period were investigated. METHODS: A retrospective review was performed of patient age and disease duration for DBS surgery for PD in UK neurosurgical units from 1997 to 2012 using departmental databases. RESULTS: The number of DBS procedures in the UK increased from three in 1997 to over 80 per year during this period. The mean age at the time of surgery (60 years) and the mean duration of PD at the time of DBS (11 years) remained unchanged over 15 years. CONCLUSIONS: The age and disease duration at which DBS is performed for PD in the UK has been static over a 15 year period and DBS appears to remain a therapy for PD applied late in its course. This may change in the light of clinical evidence suggesting a benefit for earlier DBS. PMID- 26371442 TI - Response to the comment 'Conflicting evidence on the association of white matter hyperintensities with large-artery disease'. PMID- 26371445 TI - Evidence-Based Management Of Acute Hand Injuries In The Emergency Department. AB - Although injuries of the hand are infrequently life-threatening, they are common in the emergency department and are associated with significant patient morbidity and medicolegal risk for physicians. Care of patients with acute hand injury begins with a focused history and physical examination. In most clinical scenarios, a diagnosis is achieved clinically or with plain radiographs. While most patients require straightforward treatment, the emergency clinician must rapidly identify limb-threatening injuries, obtain critical clinical information, navigate diagnostic uncertainty, and facilitate specialist consultation, when required. This review discusses the clinical evaluation and management of high morbidity hand injuries in the context of the current evidence. PMID- 26371446 TI - Outcomes of postchemotherapy retroperitoneal lymph node dissection following high dose chemotherapy with stem cell transplantation. AB - BACKGROUND: Characterizing the role of postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) after high-dose chemotherapy (HDCT) has been limited by small sample sizes. This study reports on survival after HDCT with stem cell support and PC-RPLND as well as histologic findings in the retroperitoneum. METHODS: The prospectively maintained testicular cancer database of Indiana University was queried for patients receiving HDCT with stem cell transplantation before PC-RPLND. The cause and date of death were obtained through patient chart review and contact with referring physicians. The Kaplan-Meier method was used to evaluate overall survival (OS). The log-rank test was used for tests of significance. A multivariate, backward, stepwise Cox regression model was built to evaluate predictors of overall mortality. RESULTS: A total of 92 patients were included in the study. In the entire cohort, the retroperitoneal (RP) histology findings at the time of PC-RPLND were necrosis (26%), teratoma (34%), and cancer (38%). Sixty-six patients (72%) harbored either a teratoma or active cancer in the RP specimen at PC-RPLND. The median follow-up for the entire cohort was 80.6 months. A total of 28 patients (30%) died during follow-up. The 5-year OS rate of the entire cohort was 70%. The most significant predictor of death was PC-RPLND performed in the desperation setting with elevated markers. CONCLUSIONS: Despite these patients being heavily pretreated with multiple cycles of chemotherapy, including HDCT, approximately three-fourths were found to have a teratoma and/or active cancer in the retroperitoneum. This underscores the importance of PC-RPLND for rendering patients free of disease and providing a potential for cure. PMID- 26371447 TI - The progression of thyroid cartilage calcification as it relates to the utilization of laryngeal ultrasound. AB - OBJECTIVES/HYPOTHESIS: The purpose of this study is to review the computed tomography (CT) scans of infants, children, and adults to assess the degree of calcification of the thyroid cartilage at various ages in order to understand in which age group laryngeal ultrasound can be utilized. STUDY DESIGN: Retrospective. METHODS: Two hundred patients from newborn to 50 years who received a CT scan of the neck were identified. The Hounsfield units (HU) of the thyroid cartilage were calculated at one o'clock, four o'clock, eight o'clock, and eleven o'clock at the level of the true and false vocal fold. The Spearman correlation coefficient was calculated to evaluate the correlation between each measure and age, then a linear regression with a logarithmic transformation was applied to further study how the measures were related to age. RESULTS: The Spearman correlation coefficients ranged from 0.58 to 0.75. The P values of these coefficients were all < 0.0001, showing a significant relationship to age. The age increase by 1 year resulted in increased calcification by 1.5% to 4%. The Wilcoxon signed rank test compared the rate of calcification at each site measured. This showed that the two posterolateral sites calcify faster than the two anteromedial sites. CONCLUSION: The thyroid cartilage calcifies at a rate that is significantly related to increasing age and calcifies in a posterolateral to anteromedial direction. Based on the HU, the thyroid cartilage is not consistently denser than soft tissue until greater than 40 years of age, which would make laryngeal ultrasound feasible for this population. LEVEL OF EVIDENCE: 4. PMID- 26371449 TI - Communication and relationship satisfaction in Chinese, Western, and intercultural Chinese-Western couples. AB - The current study compared Chinese, Western, and intercultural Chinese-Western couples' communication and examined how culture moderates the association of communication with relationship satisfaction. We coded the communication of 33 Western couples, 36 Chinese couples, and 54 intercultural Chinese-Western couples when discussing a relationship problem and when reminiscing about positive relationship events. Couples with Chinese female partners showed fewer positive behaviors and more negative behaviors (as classified in existing Western coding systems) than couples with Western female partners. The male partner's culture had few associations with couples' rates of communication behavior. Relationship satisfaction was associated with low rates of negative behaviors and high rates of most of the positive behaviors across cultural groups, and these associations were more evident in problem discussions than positive reminiscences. PMID- 26371448 TI - Intergenerational continuity in economic hardship, parental positivity, and positive parenting: The association with child behavior. AB - The current study examined intergenerational continuity in economic hardship, parental positivity, and positive parenting across generations based on both the family stress model (FSM) and the family resilience framework. The study included 220 generation 1 (G1) parents, their target youth (generation 2: G2) who participated from adolescence through adulthood, and the target's child (generation 3: G3). Assessments included observational and self-report measures. Results indicated that G1 economic hardship negatively influenced both G1 positivity and G1 positive parenting. Similarly, G2 economic hardship was negatively related to both G2 positivity and G2 positive parenting, which in turn was associated with G3 positive behavior to G2. For both G1 and G2, parental positivity mediated the association between economic hardship and positive parenting. G2 economic hardship was indirectly related to G3 positive behavior through G2 parental positivity and positive parenting. An important finding is that the intergenerational continuity of economic hardship, positivity, and positive parenting were transmitted from G1 to G2. Results suggest that even in times of economic adversity, parental positivity and positive parenting were transmitted from G1 parents to their G2 youth during adulthood. Such continuity seems to influence the positive behavior of the G3 children. PMID- 26371450 TI - Predictors of race, adoption, and sexual orientation related socialization of adoptive parents of young children. AB - Using a sample of 125 lesbian, gay, and heterosexual adoptive parent couples with young children (M = 6.32 years), this study examined predictors of direct socialization (preparation for adoptism, racism, and heterosexism) and indirect socialization (modeling interactions by responding to outsiders' inquiries about their child's adoptive status, racial background, or family structure). In terms of direct socialization, parents of older children tended to engage in more socialization around adoptism and heterosexism, and parents of daughters tended to engage in more socialization around racism and heterosexism. Greater perceived child interest in adoption was related to more direct socialization around adoptism. Parents of color reported more direct socialization around racism. Having a child of color was related to more direct socialization around heterosexism. Regarding indirect socialization, sexual minority parents reported more socialization around adoption and race. Greater perceived child interest in adoption was related to more indirect adoption socialization. Being more "out" was related to more indirect socialization around parent sexual orientation. PMID- 26371451 TI - Sutureless Aortic Valve Prosthesis Sizing: Estimation and Prediction Using Multidetector-Row Computed Tomography. AB - OBJECTIVE: The sutureless prostheses may facilitate minimally invasive aortic valve replacement because of easy and fast deployment. However, correct device sizing remains a crucial step of this procedure, which may be difficult and time consuming in minimal invasive approaches. We sought to analyze the accuracy of contrast-enhanced preoperative multidetector-row computed tomography (MDCT) in predicting the size of the prosthesis to be implanted in patients undergoing aortic valve replacement through a right anterior minithoracotomy (RAMT). METHODS: From January 2011 to September 2013, 235 patients underwent aortic valve surgery as sole procedure with implantation (Sorin Perceval S) in RAMT. Inclusion criterion for this study was presence of preoperative multidetector-row computed tomography (MDCT) with contrast enhancement and Doppler echocardiography. A preoperative MDCT was used to measure the aortic annulus as the diameter derived from either the area (aD) or the circumference (cD) of the virtual basal ring, left ventricular outflow tract (LVOT) diameter derived either from the area (aLVOT) or the circumference (cLVOT). Multidetector-row CT was reviewed by a single operator who was blind to implanted valve size. The operator measured the aortic annulus and LVOT in multiplanar reconstruction modality. Aortic annular diameter and LVOT diameter were retrieved from echocardiographic records. Predictive models were built based on logistic regression; outcome variable was the sutureless valve size, and covariates (annular and LVOT measurements) were used as single and multivariate predictors. A classification tree was built and then pruned with limited nodes to be able to obtain better predictive performance. RESULTS: We identified 54 patients who had preoperative contrast enhanced MDCT. Seven patients received a size S, 21 received a size M, and 26 received a size L prosthesis. The mean age of the patients at the time of intervention was 76.3 +/- 6.8 years, and the mean logistic EuroSCORE was 10.4% +/ 8.7%. Echocardiographic measurements showed lower accuracy compared to MDCT measurements. Echocardiographic LVOT measurement was 61.11% to predict the valve size, whereas annulus measurement was 53.7%. The aLVOT from MDCT had an accuracy of approximately 62.96%, and cLVOT had 64.81% predictive accuracy. Aortic annulus perimeter cD had the highest accuracy to predict the valve size [62.96%, under the curve, 0.61] followed by aortic annular surface aD having an accuracy of approximately 70.37% (under the curve, 0.75). Classification tree models, after pruning with 4 nodes, increased their accuracy (83.33%), and it was easy to interpret and possibly to implement for clinical use. CONCLUSIONS: Multidetector row CT-derived estimates seem to have higher predictive value for valve size determination in patients undergoing RAMT with the Perceval S prosthesis, thus facilitating this delicate procedure and preventing the selection of wrong candidates. Possibly for precise aortic annulus measurement, contrast-enhanced MDCT is preferable. PMID- 26371452 TI - ISMICS Consensus Conference and Statements of Randomized Controlled Trials of Off Pump Versus Conventional Coronary Artery Bypass Surgery. AB - OBJECTIVE: At this consensus conference, we developed evidence-informed consensus statements and recommendations on the practice of off-pump coronary artery bypass graft (OPCAB) by systematically reviewing and performing meta-analysis of the randomized controlled trials (RCTs) comparing OPCAB and conventional coronary artery bypass (CCAB). METHODS: All RCTs of OPCAB versus CCAB through April 2013 were screened, and 102 relevant RCTs (19,101 patients) were included in a systematic review and meta-analysis (15 RCTs of 9551 high-risk patients; and 87 RCTs of 9550 low-risk patients) in accordance with the Cochrane Collaboration and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) methodology. Consensus statements for the risks and benefits of OPCAB surgery in mortality, morbidity, and resource use were developed based on best available evidence. RESULTS: Compared to CCAB, it is reasonable to perform OPCAB to reduce risks of stroke [class IIa, level of evidence (LOE) A], renal dysfunction/failure (class IIa, LOE A), blood transfusion (class I, LOE A), respiratory failure (class I, LOE A), atrial fibrillation (class I, LOE A), wound infection (class I, LOE A), ventilation time, and ICU and hospital length of stay (class I, LOE A). However, OPCAB may be associated with a reduced number of grafts performed (class I, LOE A) and with diminished graft patency (class IIa, LOE A, with increased coronary reintervention at 1 year and beyond (class IIa, LOE A), as well as increased mortality at a median follow-up of 5 years (class IIb, LOE A). CONCLUSIONS: OPCAB compared with CCAB may improve outcomes in the short-term (stroke, renal dysfunction, blood transfusion, respiratory failure, atrial fibrillation, wound infection, ventilation time, and length of stay). However, over the longer-term, OPCAB may be associated with reduced graft patency, and increased risk of cardiac re-intervention and death. PMID- 26371454 TI - Erratum. PMID- 26371453 TI - Single-Center Experience With Adjustable Annuloplasty Ring in Degenerative Mitral Regurgitation. AB - OBJECTIVE: Owing to the complex anatomy of the mitral valve, successful surgical repair of degenerative regurgitation remains a challenging procedure in cardiac surgery. METHODS: This paper aimed to report on our single-center experience with 20 patients who received an adjustable annuloplasty ring (Cardinal ring, ValtechCardio Ltd, Or Yehuda, Israel) as part of their mitral valve repair procedure. The device allows for intraoperative echocardiography-guided ring size adjustments under beating-heart conditions. RESULTS: All of the 20 patients left the operating room without any residual mitral regurgitation. There was no risk of systolic anterior movement (SAM) because of image-guided fine tuning of the ring before weaning the patient from bypass. CONCLUSIONS: Further multicenter data are required to prove the concept of adjustable annuloplasty devices. PMID- 26371455 TI - Gray matter abnormalities in patients with social anxiety disorder: A voxel-based morphometry study. AB - The main objective of this study was to investigate the gray matter volume (GMV) differences between the patients with social anxiety disorder (SAD) and healthy controls, using VBM analysis. A total of 27 consecutive patients (15 women and 12 men) with SAD and 27 age and sex-matched healthy control subjects were included in this study. With magnetic resonance imaging, we examined GMV differences between SAD and healthy control groups. We found that GMV in the right middle and inferior temporal, left superior parietal, left precuneus and right fusiform areas were significantly greater in patients with SAD than in healthy controls. In addition, GMV in the right inferior and middle temporal regions were positively correlated with the social avoidance and total social anxiety scores of the participants in the SAD group. Lastly, greater GMV in the left superior parietal and precuneal regions were correlated with the higher disability in the social life of the patients with SAD. Our results suggest that the regions that showed significant GMV differences between the two groups play an important role in the pathophysiology of SAD and increased GMV in these regions might reflect a pathological process of neural abnormalities in this disorder. PMID- 26371456 TI - Transcranial sonography of brainstem structures in panic disorder. AB - Panic disorder has been associated with altered serotonin metabolism in the brainstem raphe. The aim of study was to evaluate the BR echogenicity on transcranial sonography (TCS) in panic disorder. A total of 96 healthy volunteers were enrolled in the "derivation" cohort, and 26 healthy volunteers and 26 panic disorder patients were enrolled in the "validation" cohort. TCS echogenicity of brainstem raphe and substantia nigra was assessed on anonymized images visually and by means of digitized image analysis. Significantly reduced brainstem raphe echogenicity was detected more frequently in panic disorder patients than in controls using both visual (68% vs. 31%) and digitized image analysis (52% vs. 12%). The optimal cut-off value of digitized brainstem raphe echogenicity indicated the diagnosis of panic disorder with a sensitivity of 64% and a specificity of 73%, and corresponded to the 30th percentile in the derivation cohort. Reduced brainstem raphe echogenicity was associated with shorter treatment duration, and, by trend, lower severity of anxiety. No relationship was found between echogenicity of brainstem raphe or substantia nigra and age, gender, severity of panic disorder, or severity of depression. Patients with panic disorder exhibit changes of brainstem raphe on TCS suggesting an alteration of the central serotonergic system. PMID- 26371458 TI - Natural Tooth Color Estimation Based on Age and Gender. AB - PURPOSE: Assessment of the predictability of tooth color coordinates according to the CIELab system to estimate the color of the maxillary central incisor based on patient age and gender. MATERIAL AND METHODS: The tooth color of one of the maxillary central incisors of 1361 Caucasian Spanish individuals aged 16 to 89 years, male and female, was measured using the Easyshade compact spectrophotometer. Color coordinates L*, C*, h*, a*, and b* were recorded according to age and gender. RESULTS: The results obtained show that differences in age account for 45% of the total variation of the L (lightness) coordinate; 21% of the variation in coordinate a*, and 17% of the variation in coordinate b* is due to the same reason. At a confidence level of 95% it may be proposed that the mean estimated color difference (DeltaEab *) between real natural color and that predicted by the linear regression model is between 6.4 and 6.9 units. CONCLUSIONS: In this sample of Caucasians from Spain, teeth became darker yellow and more reddish with increasing age. The L* coordinate is most strongly related to tooth color in aging. PMID- 26371457 TI - Productivity costs decrease after endoscopic sinus surgery for refractory chronic rhinosinusitis. AB - OBJECTIVES/HYPOTHESIS: The primary objective of this pilot study was to define the change in productivity costs following endoscopic sinus surgery (ESS) for chronic rhinosinusitis (CRS). Secondary objectives were to identify CRS-related characteristics that may influence the degree of productivity improvement after ESS. STUDY DESIGN: Prospective, multi-institutional, observational cohort study. METHODS: The human capital approach was used to define productivity costs. Annual absenteeism, presenteeism, and lost leisure time were quantified to define annual lost productive time (LPT). LPT was monetized using the annual daily wage rates obtained from the 2012 US Census and the 2013 US Department of Labor statistics. RESULTS: Twenty-seven patients with refractory CRS who underwent ESS were followed for a mean of 15 months (range, 8-25 months). Following ESS, there were improvements in annual absenteeism (22 days reduced to 3 days), annual presenteeism (41 days reduced to 19 days), and annual household days lost (12 days reduced to 6 days). Overall, the preoperative productivity costs were reduced after ESS ($9,190 vs. $3,373, respectively; P < .001). CONCLUSIONS: Daily productivity is negatively impacted by the presence of CRS. The outcomes from this study provide the first insights into the reduced productivity costs associated with receiving ESS for refractory CRS. Future studies with larger sample sizes will need to validate the results from this pilot study. LEVEL OF EVIDENCE: 2c Laryngoscope, 126:570-574, 2016. PMID- 26371459 TI - Physiological Responses to Indoor Versus Outdoor Training in Postmenopausal Women. AB - Chronic effects of two different exercise environments on self-chosen intensity and physiological adaptations were examined in postmenopausal women. Twenty-three healthy to overweight (body mass index [BMI] 22-29 kg/m2) postmenopausal women performed three weekly training sessions during 12 weeks and were assigned to either: (1) indoor training or (2) outdoor training. Body composition, metabolic profile, and physical fitness (including Vo2max, maximal strength, and endurance) were assessed pre- and postintervention. Exercise intensity was measured every week during the training. Maximum intensity decreased significantly in time only in outdoor training (p <= .05). Body composition and VO2max were significantly improved indoors (p <= .05), whereas resting blood pressure and upper body maximal strength and endurance were improved outdoors (p <= .05). Indoor training is associated with maintaining intensity over time and slightly higher physiological improvements than outdoor training. However, outdoor training seems promising from a long-term perspective, due to its positive effects on health parameters and exercise adherence. PMID- 26371460 TI - The HIV treatment cascade in acutely infected people: informing global guidelines. AB - PURPOSE OF REVIEW: Acute and early HIV (AHI) is a pivotal time during HIV infection, yet there remain major shortfalls in diagnosis, linkage to care, and antiretroviral therapy (ART) initiation during AHI. We introduce an AHI-specific cascade, review recent evidence pertaining to the unique challenges of AHI, and discuss strategies for improving individual and public health outcomes. RECENT FINDINGS: Presentation during AHI is common. Expanding use of fourth-generation testing and pooled nucleic acid amplification testing has led to improved AHI detection in resource-wealthy settings. Technologies capable of AHI diagnosis are rare in resource-limited settings; further development of point-of-care devices and utilization of targeted screening is needed. Rapid ART initiation during AHI limits reservoir seeding, preserves immunity, and prevents transmission. Reporting of AHI cascade outcomes is limited, but new evidence suggests that impressive rates of diagnosis, linkage to care, rapid ART initiation, and viral suppression can be achieved. SUMMARY: With advancements in AHI diagnostics and strong evidence for the therapeutic and prevention benefits of ART initiated during AHI, improving AHI cascade outcomes is both crucial and feasible. HIV guidelines should recommend diagnostic algorithms capable of detecting AHI and prescribe rapid, universal ART initiation during AHI. PMID- 26371461 TI - Financial incentives to improve progression through the HIV treatment cascade. AB - PURPOSE OF REVIEW: We reviewed recent literature on conditional and unconditional financial incentives for their impact on improving movement through the HIV care cascade and HIV prevention. RECENT FINDINGS: Concepts from behavioral economics may help improve engagement in HIV care by addressing upstream structural risk factors for HIV, such as poverty, or providing conditional rewards for immediate, measurable outcomes related to HIV care. Incentives have been shown to increase uptake of HIV testing. Yet, few studies to date focus on linkage to care: one large USA-based randomized trial failed to show an effect of incentives; and a smaller trial showed improved linkage to care among drug users, but no difference in virologic suppression. Several small USA-based studies have shown an impact of financial incentives on antiretroviral therapy adherence, but without durability beyond the incentive period. HIV prevention has the most robust evidence for decreasing HIV risk-taking behavior among adolescents and may serve as a model for research on the care cascade. SUMMARY: Financial incentives show promise for improving engagement in HIV testing, care, and prevention. Understanding the durability, scalability, ease of implementation, and cost-effectiveness of these different approaches will be critical for maximizing the impact of incentives in curtailing the HIV epidemic. PMID- 26371463 TI - Quasi-experiments to establish causal effects of HIV care and treatment and to improve the cascade of care. AB - PURPOSE OF REVIEW: Randomized, population-representative trials of clinical interventions are rare. Quasi-experiments have been used successfully to generate causal evidence on the cascade of HIV care in a broad range of real-world settings. RECENT FINDINGS: Quasi-experiments exploit exogenous, or quasi-random, variation occurring naturally in the world or because of an administrative rule or policy change to estimate causal effects. Well designed quasi-experiments have greater internal validity than typical observational research designs. At the same time, quasi-experiments may also have potential for greater external validity than experiments and can be implemented when randomized clinical trials are infeasible or unethical. Quasi-experimental studies have established the causal effects of HIV testing and initiation of antiretroviral therapy on health, economic outcomes and sexual behaviors, as well as indirect effects on other community members. Recent quasi-experiments have evaluated specific interventions to improve patient performance in the cascade of care, providing causal evidence to optimize clinical management of HIV. SUMMARY: Quasi-experiments have generated important data on the real-world impacts of HIV testing and treatment and on interventions to improve the cascade of care. With the growth in large-scale clinical and administrative data, quasi-experiments enable rigorous evaluation of policies implemented in real-world settings. PMID- 26371464 TI - Nanoparticle-based imaging of inflammatory bowel disease. AB - Although inflammatory bowel disease (IBD) has been extensively studied, the pathogenesis is still not completely understood. As a result, the treatment options remain unsatisfactory and nonspecific. With the rapid advancement of diagnostic imaging techniques, imaging modalities such as computed tomography (CT) and magnetic resonance imaging (MRI) are playing a more important role in IBD diagnosis and evaluation. Recent developments in nanotechnology utilize an interdisciplinary approach to specifically target molecular or cellular IBD pathological process thereby generating nanoparticles (NPs) with high specificity and diagnostic and/or therapeutic efficacy. Nano-based imaging, which incorporates nanotechnology and imaging modalities, may allow for the early detection of IBD, the monitoring of disease activity, and may be used to monitor the therapeutic response at cellular and/or molecular level. In this review, we highlight issues related to nano-based imaging and its application in IBD field. PMID- 26371465 TI - Eyelid Lacerations Due to Dog Bite in Children. AB - PURPOSE: To evaluate the nature and extent of lacrimal apparatus injury in children after eyelid laceration from a dog bite. METHODS: A retrospective chart review of all eyelid lacerations treated between 1990 and 2012 at Boston Children's Hospital, Boston, Massachusetts, was conducted. Seventy-three patients who sustained an eyelid laceration due to dog bite were identified and were matched 5:1 with a randomly selected cohort of 365 patients from the group of 1,177 patients who had sustained eyelid lacerations from other causes during the same time period. RESULTS: Of the 73 patients who sustained an eyelid laceration due to a dog bite, 26 (35.62%) had damage to the lacrimal apparatus. This was statistically significant when compared to patients who sustained eyelid lacerations from other causes, in which 13 (3.56%) patients had damage to the lacrimal apparatus (P < .000001). The inferior canaliculus was the most commonly involved site of lacrimal apparatus trauma as a result of a dog bite. Success was defined as lack of epiphora at the time of the last follow-up. Early surgical management of eyelid lacerations with lacrimal apparatus involvement had a success rate of 82%. CONCLUSIONS: Eyelid lacerations due to dog bites have a greater prevalence of involvement of the lacrimal apparatus and especially the inferior canaliculus than lacerations due to other causes in children. Clinicians should have a high index of suspicion for lacrimal apparatus involvement and be prepared for surgical repair, if indicated. PMID- 26371462 TI - Innovations in health and demographic surveillance systems to establish the causal impacts of HIV policies. AB - PURPOSE OF REVIEW: Health and demographic surveillance systems (HDSS), in conjunction with HIV treatment cohorts, have made important contributions to our understanding of the impact of HIV treatment and treatment-related interventions in sub-Saharan Africa. The purpose of this review is to describe and discuss innovations in data collection and data linkage that will create new opportunities to establish the impacts of HIV treatment, as well as policies affecting the treatment cascade, on population health and economic and social outcomes. RECENT FINDINGS: Novel approaches to routine collection of biomarkers, behavioural data, spatial data, social network information, migration events and mobile phone records can significantly strengthen the potential of HDSS to generate exposure and outcome data for causal analysis of HIV treatment impact and policies affecting the HIV treatment cascade. Additionally, by linking HDSS data to health service administration, education and welfare service records, researchers can substantially broaden opportunities to establish how HIV treatment affects health and economic outcomes when delivered through public sector health systems and at scale. SUMMARY: As the HIV treatment scaleup in sub Saharan Africa enters its second decade, it is becoming increasingly important to understand the long-term causal impacts of large-scale HIV treatment and related policies on broader population health outcomes, such as noncommunicable diseases, as well as on economic and social outcomes, such as family welfare and children's educational attainment. By collecting novel data and linking existing data to public sector records, HDSS can create near-unique opportunities to contribute to this research agenda. PMID- 26371467 TI - Exponential size-dependent tunability of strain on the transport behavior in ZnO tunnel junctions: an ab initio study. AB - It is an interesting issue if the transport behavior of a piezoelectric tunnel junction is sensitive to external strain or stress, and it implies a prospect for developing novel mechanical sensors, transducers, piezotronic devices, etc. Many studies paid attention to this issue, yet how the strain and stress tunable transport behavior of a tunnel junction depends on the barrier thickness is still rarely known. Using the first principles calculations, we investigate the size dependent and strain-tunable transport behavior in the tunnel junctions. It was confirmed that external strain has strong control over the transport properties of ZnO tunnel junctions, with several times amplification of tunnel conductance obtained by strain reversal. More importantly, the conductance amplification by strain reversal exponentially changes with the barrier thickness, indicating the size-dependent strain tunability of the transport behavior. The electrostatic quantities (i.e., built-in field, depolarization field, polarization, interfacial dipoles and potential barrier) and the transport properties of tunnel junctions were comprehensively analyzed to reveal the relationships between these quantities and their size dependence. The exponential size-dependence of strain tunable transport behavior in ZnO tunnel junctions is attributed to the linear change in the potential barrier with the barrier thickness. Our simulations provide an insight of how to maximize the strain tunability of transport behavior of piezoelectric tunnel junctions by thickness design and strain engineering. PMID- 26371468 TI - Liposomes Combined an Integrin alphavbeta3-Specific Vector with pH-Responsible Cell-Penetrating Property for Highly Effective Antiglioma Therapy through the Blood-Brain Barrier. AB - Glioma, one of the most common aggressive malignancies, has the highest mortality in the present world. Delivery of nanocarriers from the systemic circulation to the glioma sites would encounter multiple physiological and biological barriers, such as blood-brain barrier (BBB) and the poor penetration of nanocarriers into the tumor. To circumvent these hurdles, the paclitaxel-loaded liposomes were developed by conjugating with a TR peptide (PTX-TR-Lip), integrin alphavbeta3 specific vector with pH-responsible cell-penetrating property, for transporting drug across the BBB and then delivering into glioma. Surface plasmon resonance (SPR) studies confirmed the very high affinity of TR-Lip and integrin alphavbeta3. In vitro results showed that TR-Lip exhibited strong transport ability across BBB, killed glioma cells and brain cancer stem cells (CSCs), and destroyed the vasculogenic mimicry (VM) channels. In vivo results demonstrated that TR-Lip could better target glioma, and eliminated brain CSCs and the VM channels in tumor tissues. The median survival time of tumor-bearing mice after administering PTX-TR-Lip (45 days) was significantly longer than that after giving free PTX (25.5 days, p < 0.001) or other controls. In conclusion, PTX-TR Lip would improve the therapeutic efficacy of brain glioma in vitro and in vivo. PMID- 26371469 TI - Seed plant phylogenetic diversity and species richness in conservation planning within a global biodiversity hotspot in eastern Asia. AB - One of the main goals of conservation biology is to understand the factors shaping variation in biodiversity across the planet. This understanding is critical for conservation planners to be able to develop effective conservation strategies. Although many studies have focused on species richness and the protection of rare and endemic species, less attention has been paid to the protection of the phylogenetic dimension of biodiversity. We explored how phylogenetic diversity, species richness, and phylogenetic community structure vary in seed plant communities along an elevational gradient in a relatively understudied high mountain region, the Dulong Valley, in southeastern Tibet, China. As expected, phylogenetic diversity was well correlated with species richness among the elevational bands and among communities. At the community level, evergreen broad-leaved forests had the highest levels of species richness and phylogenetic diversity. Using null model analyses, we found evidence of nonrandom phylogenetic structure across the region. Evergreen broad-leaved forests were phylogenetically overdispersed, whereas other vegetation types tended to be phylogenetically clustered. We suggest that communities with high species richness or overdispersed phylogenetic structure should be a focus for biodiversity conservation within the Dulong Valley because these areas may help maximize the potential of this flora to respond to future global change. In biodiversity hotspots worldwide, we suggest that the phylogenetic structure of a community may serve as a useful measure of phylogenetic diversity in the context of conservation planning. PMID- 26371470 TI - Community-Effectiveness of Temephos for Dengue Vector Control: A Systematic Literature Review. AB - The application of the organophosphate larvicide temephos to water storage containers is one of the most commonly employed dengue vector control methods. This systematic literature review is to the knowledge of the authors the first that aims to assess the community-effectiveness of temephos in controlling both vectors and dengue transmission when delivered either as a single intervention or in combination with other interventions. A comprehensive literature search of 6 databases was performed (PubMed, WHOLIS, GIFT, CDSR, EMBASE, Wiley), grey literature and cross references were also screened for relevant studies. Data were extracted and methodological quality of the studies was assessed independently by two reviewers. 27 studies were included in this systematic review (11 single intervention studies and 16 combined intervention studies). All 11 single intervention studies showed consistently that using temephos led to a reduction in entomological indices. Although 11 of the 16 combined intervention studies showed that temephos application together with other chemical vector control methods also reduced entomological indices, this was either not sustained over time or-as in the five remaining studies--failed to reduce the immature stages. The community-effectiveness of temephos was found to be dependent on factors such as quality of delivery, water turnover rate, type of water, and environmental factors such as organic debris, temperature and exposure to sunlight. Timing of temephos deployment and its need for reapplication, along with behavioural factors such as the reluctance of its application to drinking water, and operational aspects such as cost, supplies, time and labour were further limitations identified in this review. In conclusion, when applied as a single intervention, temephos was found to be effective at suppressing entomological indices, however, the same effect has not been observed when temephos was applied in combination with other interventions. There is no evidence to suggest that temephos use is associated with reductions in dengue transmission. PMID- 26371471 TI - The Use of a Mercury Biosensor to Evaluate the Bioavailability of Mercury-Thiol Complexes and Mechanisms of Mercury Uptake in Bacteria. AB - As mercury (Hg) biosensors are sensitive to only intracellular Hg, they are useful in the investigation of Hg uptake mechanisms and the effects of speciation on Hg bioavailability to microbes. In this study, bacterial biosensors were used to evaluate the roles that several transporters such as the glutathione, cystine/cysteine, and Mer transporters play in the uptake of Hg from Hg-thiol complexes by comparing uptake rates in strains with functioning transport systems to strains where these transporters had been knocked out by deletion of key genes. The Hg uptake into the biosensors was quantified based on the intracellular conversion of inorganic mercury (Hg(II)) to elemental mercury (Hg(0)) by the enzyme MerA. It was found that uptake of Hg from Hg-cysteine (Hg(CYS)2) and Hg-glutathione (Hg(GSH)2) complexes occurred at the same rate as that of inorganic complexes of Hg(II) into Escherichia coli strains with and without intact Mer transport systems. However, higher rates of Hg uptake were observed in the strain with a functioning Mer transport system. These results demonstrate that thiol-bound Hg is bioavailable to E. coli and that this bioavailability is higher in Hg-resistant bacteria with a complete Mer system than in non-resistant strains. No difference in the uptake rate of Hg from Hg(GSH)2 was observed in E. coli strains with or without functioning glutathione transport systems. There was also no difference in uptake rates between a wildtype Bacillus subtilis strain with a functioning cystine/cysteine transport system, and a mutant strain where this transport system had been knocked out. These results cast doubt on the viability of the hypothesis that the entire Hg thiol complex is taken up into the cell by a thiol transporter. It is more likely that the Hg in the Hg-thiol complex is transferred to a transport protein on the cell membrane and is subsequently internalized. PMID- 26371472 TI - Release of Periplasmic Nucleotidase Induced by Human Antimicrobial Peptide in E. coli Causes Accumulation of the Immunomodulator Adenosine. AB - Previous work by our group described that human beta-defensin-2 induces accumulation of extracellular adenosine (Ado) in E. coli cultures through a non lytic mechanism causing severe plasmolysis. Here, we investigate the presence of AMP as a direct precursor and the involvement of a bacterial enzyme in the generation of extracellular Ado by treated bacteria. Following hBD-2 treatment, metabolites were quantified in the supernatants using targeted HPLC-MS/MS analysis. Microbial growth was monitored by optical density and cell viability was determined by colony forming units counts. Phosphatase activity was measured using chromogenic substrate pNPP. The results demonstrate that defensin-treated E. coli strain W releases AMP in the extracellular space, where it is converted to Ado by a bacterial soluble factor. An increase in phosphatase activity in the supernatant was observed after peptide treatment, similar to the effect of sucrose-induced osmotic stress, suggesting that the periplasmic 5'nucleotidase (5'-NT) is released following the plasmolysis event triggered by the peptide. Ado accumulation was enhanced in the presence of Co2+ ion and inhibited by EDTA, further supporting the involvement of a metallo-phosphatase such as 5'-NT in extracellular AMP conversion into Ado. The comparative analysis of hBD-induced Ado accumulation in different E. coli strains and in Pseudomonas aeruginosa revealed that the response is not correlated to the peptide's effect on cell viability, but indicates it might be dependent on the subcellular distribution of the nucleotidase. Taken together, these data shed light on a yet undescribed mechanism of host-microbial interaction: a human antimicrobial peptide inducing selective release of a bacterial enzyme (E. coli 5'-NT), leading to the formation of a potent immunomodulator metabolite (Ado). PMID- 26371473 TI - Advantages and Challenges of A Village Doctor-Based Cognitive Behavioral Therapy for Late-Life Depression in Rural China: A Qualitative Study. AB - BACKGROUND: The delivery of mental health services in rural China has been notably limited due to lack of qualified mental health professionals among other impeding factors. A village doctor-based cognitive behavioral therapy intervention may be one way of improving accessibility. The purpose of this study was to explore the advantages and challenges of implementing this intervention, as delivered by trained village doctors, to treat late-life depression in rural China. METHODS: We conducted one focus group discussion with 10 village doctors, 10 individual interviews with each of the village doctors, and individual interviews with 19 older adults. The topic guides were advantages and challenges of the intervention program from the perspective of the village doctors and older adults. Interviews were audio-recorded, transcribed, coded using NVivo 8, and analyzed using thematic analysis. RESULTS: The village doctors stressed the importance of role-playing and using instructive manuals in the training. Proper supervision was also a key component of the program. The benefits received from the intervention for the village doctors and the elders were positive such that both the doctors and the older adults were willing to implement/receive this intervention. Cultural and political factors (renqing and perceived policy consideration) facilitated the elders' access to mental health services. Challenges included a lack of real therapy (in contrast to role-playing) demonstrated in the training and lack of a step-by-step manual based on different types of problems encountered. Other impediments to the successful implementation of the intervention included the time constraints of village doctors and the presence of other people when conducting the intervention. CONCLUSIONS: The present study has demonstrated that the intervention program is likely to be an acceptable geriatric depression intervention in rural China if several challenges are appropriately addressed. PMID- 26371474 TI - Mass-Specific Metabolic Rate Influences Sperm Performance through Energy Production in Mammals. AB - Mass-specific metabolic rate, the rate at which organisms consume energy per gram of body weight, is negatively associated with body size in metazoans. As a consequence, small species have higher cellular metabolic rates and are able to process resources at a faster rate than large species. Since mass-specific metabolic rate has been shown to constrain evolution of sperm traits, and most of the metabolic activity of sperm cells relates to ATP production for sperm motility, we hypothesized that mass-specific metabolic rate could influence sperm energetic metabolism at the cellular level if sperm cells maintain the metabolic rate of organisms that generate them. We compared data on sperm straight-line velocity, mass-specific metabolic rate, and sperm ATP content from 40 mammalian species and found that the mass-specific metabolic rate positively influences sperm swimming velocity by (a) an indirect effect of sperm as the result of an increased sperm length, and (b) a direct effect independent of sperm length. In addition, our analyses show that species with higher mass-specific metabolic rate have higher ATP content per sperm and higher concentration of ATP per MUm of sperm length, which are positively associated with sperm velocity. In conclusion, our results suggest that species with high mass-specific metabolic rate have been able to evolve both long and fast sperm. Moreover, independently of its effect on the production of larger sperm, the mass-specific metabolic rate is able to influence sperm velocity by increasing sperm ATP content in mammals. PMID- 26371475 TI - Functional Characterization of Human ProNGF and NGF Mutants: Identification of NGF P61SR100E as a "Painless" Lead Investigational Candidate for Therapeutic Applications. AB - BACKGROUND: Nerve Growth Factor (NGF) holds a great therapeutic promise for Alzheimer's disease, diabetic neuropathies, ophthalmic diseases, dermatological ulcers. However, the necessity for systemic delivery has hampered the clinical applications of NGF due to its potent pro-nociceptive action. A "painless" human NGF (hNGF R100E) mutant has been engineered. It has equal neurotrophic potency to hNGF but a lower nociceptive activity. We previously described and characterized the neurotrophic and nociceptive properties also of the hNGF P61S and P61SR100E mutants, selectively detectable against wild type hNGF. However, the reduced pain sensitizing potency of the "painless" hNGF mutants has not been quantified. OBJECTIVES AND RESULTS: Aiming at the therapeutic application of the "painless" hNGF mutants, we report on the comparative functional characterization of the precursor and mature forms of the mutants hNGF R100E and hNGF P61SR100E as therapeutic candidates, also in comparison to wild type hNGF and to hNGF P61S. The mutants were assessed by a number of biochemical, biophysical methods and assayed by cellular assays. Moreover, a highly sensitive ELISA for the detection of the P61S-tagged mutants in biological samples has been developed. Finally, we explored the pro-nociceptive effects elicited by hNGF mutants in vivo, demonstrating an expanded therapeutic window with a ten-fold increase in potency. CONCLUSIONS: This structure-activity relationship study has led to validate the concept of developing painless NGF as a therapeutic, targeting the NGF receptor system and supporting the choice of hNGF P61S R100E as the best candidate to advance in clinical development. Moreover, this study contributes to the identification of the molecular determinants modulating the properties of the hNGF "painless" mutants. PMID- 26371476 TI - Skin-Derived C-Terminal Filaggrin-2 Fragments Are Pseudomonas aeruginosa-Directed Antimicrobials Targeting Bacterial Replication. AB - Soil- and waterborne bacteria such as Pseudomonas aeruginosa are constantly challenging body surfaces. Since infections of healthy skin are unexpectedly rare, we hypothesized that the outermost epidermis, the stratum corneum, and sweat glands directly control the growth of P. aeruginosa by surface-provided antimicrobials. Due to its high abundance in the upper epidermis and eccrine sweat glands, filaggrin-2 (FLG2), a water-insoluble 248 kDa S100 fused-type protein, might possess these innate effector functions. Indeed, recombinant FLG2 C-terminal protein fragments display potent antimicrobial activity against P. aeruginosa and other Pseudomonads. Moreover, upon cultivation on stratum corneum, P. aeruginosa release FLG2 C-terminus-containing FLG2 fragments from insoluble material, indicating liberation of antimicrobially active FLG2 fragments by the bacteria themselves. Analyses of the underlying antimicrobial mechanism reveal that FLG2 C-terminal fragments do not induce pore formation, as known for many other antimicrobial peptides, but membrane blebbing, suggesting an alternative mode of action. The association of the FLG2 fragment with the inner membrane of treated bacteria and its DNA-binding implicated an interference with the bacterial replication that was confirmed by in vitro and in vivo replication assays. Probably through in situ-activation by soil- and waterborne bacteria such as Pseudomonads, FLG2 interferes with the bacterial replication, terminates their growth on skin surface and thus may contributes to the skin's antimicrobial defense shield. The apparent absence of FLG2 at certain body surfaces, as in the lung or of burned skin, would explain their higher susceptibility towards Pseudomonas infections and make FLG2 C-terminal fragments and their derivatives candidates for new Pseudomonas-targeting antimicrobials. PMID- 26371477 TI - Association of Relapse with Renal Outcomes under the Current Therapy Regimen for IgA Nephropathy: A Multi-Center Study. AB - BACKGROUND AND OBJECTIVES: Renal relapse is a very common manifestation of IgA nephropathy (IgAN). The clinical characteristics and long-term outcomes of this condition have not yet been carefully explored. DESIGN AND PATIENTS: Patients with biopsy-proven IgAN between January 2005 and December 2010 from three medical centers in China was a primary cohort of patients. From January 2010 to April 2012, data of an independent cohort of IgAN patients from Ren Ji Hospital, Shanghai, China was collected using the same inclusion and exclusion criteria. These patients formed the validation cohort of this study. RESULTS: Of the patients with biopsy-proven IgAN from three medical centers, 489 patients achieved remission within 6 months following the therapy. Additionally, 76 (15.5%) of these patients experienced a relapse after achieving remission. During the median follow-up period of 66 months, 6 patients (1.4%) in the non-relapse group experienced renal deterioration, compared with 22 patients (29.6%) in the relapse group. Our study indicated that each 1-mmHg increase in the baseline diastolic blood pressure (DBP) was associated with a 4.5% increase in the risk of renal relapse; additionally, the male patients had a 3.324-fold greater risk of relapse compared with the female patients according to the adjusted multivariate Cox analysis. The nomogram was based on 489 patients achieved remission. The predictive accuracy and discriminative ability of the nomogram were determined by concordance index (C-index) and calibration curve. The results were validated using bootstrap resampling on the validation cohort. CONCLUSIONS: This study demonstrated that renal relapse is a potential predictor of prognostic outcomes in patients under the current therapeutic regimens for IgAN. And male patients with higher diastolic blood pressure had a greater risk of experiencing relapse. PMID- 26371479 TI - [Treatment of alcohol dependence in primary health care can provide good results. The 15-method--a structured care model matched to patient needs]. AB - The main obstacle for people with an alcohol problem to seek help is the stigma attached to alcohol problems and alcohol treatment. Seeking help in primary health care is less stigmatised. Alcohol dependence is mostly of mild or moderate severity and can consequently be managed by non-specialists to a large extent. The 15-method is a structured stepped care model with evidence-based components, where interventions are matched to patient need. The first step, to recognise the impact of alcohol on health, should be mastered by all health professionals. PMID- 26371478 TI - Plastid Proteomic Analysis in Tomato Fruit Development. AB - To better understand the mechanism of plastid differentiation from chloroplast to chromoplast, we examined proteome and plastid changes over four distinct developmental stages of 'Micro-Tom' fruit. Additionally, to discover more about the relationship between fruit color and plastid differentiation, we also analyzed and compared 'Micro-Tom' results with those from two other varieties, 'Black' and 'White Beauty'. We confirmed that proteins related to photosynthesis remain through the orange maturity stage of 'Micro-Tom', and also learned that thylakoids no longer exist at this stage. These results suggest that at a minimum there are changes in plastid morphology occurring before all related proteins change. We also compared 'Micro-Tom' fruits with 'Black' and 'White Beauty' using two-dimensional gel electrophoresis. We found a decrease of CHRC (plastid-lipid associated protein) and HrBP1 (harpin binding protein-1) in the 'Black' and 'White Beauty' varieties. CHRC is involved in carotenoid accumulation and stabilization. HrBP1 in Arabidopsis has a sequence similar to proteins in the PAP/fibrillin family. These proteins have characteristics and functions similar to lipocalin, an example of which is the transport of hydrophobic molecules. We detected spots of TIL (temperature-induced lipocalin) in 2D-PAGE results, however the number of spots and their isoelectric points differed between 'Micro-Tom' and 'Black'/'White Beauty'. Lipocalin has various functions including those related to environmental stress response, apoptosis induction, membrane formation and fixation, regulation of immune response, cell growth, and metabolism adjustment. Lipocalin related proteins such as TIL and HrBP1 could be related to the accumulation of carotenoids, fruit color and the differentiation of chromoplast. PMID- 26371480 TI - [Severe ketoacidosis in breastfeeding woman with low energy and carbohydrate intake]. AB - Ketoacidosis is a life threatening condition usually caused by diabetes mellitus or alcohol. In this case report we present a lactating woman who developed a severe ketoacidosis a few weeks post partum. Her nutritional status was inadequate due to illness and a diet low on carbohydrates. Five case reports regarding ketoacidosis in lactating women have previously been described in the literature. This case report highlights the importance of nutrition during periods of breast feeding. PMID- 26371481 TI - [New routines in orthopedics department yielded more efficient care and more satisfied patients. Physiotherapist and team make the first assessment in new visits to the spine surgeon]. AB - There is a shortage of spine surgeons in Sweden. To guarantee the legal right to healthcare, many counties must hire doctors, with increasing costs. In our new out-patient department routine, the majority of the patients are examined by a physiotherapist at their first visit. History taking and clinical and radiographic examinations are discussed in a team conference, and possible candidates for spine surgery are selected for an appointment with a spine surgeon. Furthermore, the patients were more satisfied with the new routine and management plan. PMID- 26371482 TI - [Systematic medical record review in Skane. Diagnostic codes were often wrong in severe sepsis and septic shock]. AB - The reliability of official registers of diagnosis depends on proper adherence to guidelines for diagnosis and diagnosis coding. Such guidelines for severe sepsis and septic shock have changed over the years, reflecting improved knowledge of these serious conditions. In order to investigate the compliance to current Swedish guidelines for diagnosis and coding of severe sepsis and septic shock, we studied the medical records from 300 patients with Escherichia coli bacteremia and 300 patients with Staphylococcus aureus bacteremia. Our study showed that out of 161 patients who fulfilled the criteria for either severe sepsis or septic shock, only 29 (18%) received an accurate diagnosis code. Thus, severe sepsis appears to be underappreciated in official registers of diagnosis in Sweden. It is important to improve the adherence to the present diagnosis guidelines in order for the registers to be reliable. PMID- 26371483 TI - [Midwives in rural Uganda. Treating incomplete abortions and miscarriages safe and effectively]. PMID- 26371484 TI - [Triglycerides--a long known risk factor for cardiovascular disease. Subgroup analysis shows the importance after acute coronary syndrome]. AB - An increased blood concentration of triglycerides (TG) has long been recognized as an important risk factor for cardiovascular disease. Through competition from HDL cholesterol and the arrival of statin treatment for high LDL cholesterol the importance of TG as risk factor was largely forgotten. A high concentration of TG indicates high blood levels of TG-rich lipoproteins including cholesterol rich remnant particles. Studies using Mendelian randomizations have demonstrated that a low HDL cholesterol does not carry a direct atherogenic function and that remnant particles do so. New efforts should be exercised in order to diminish residual cardiovascular risk during statin treatment through decreasing TG rich lipoproteins. PMID- 26371485 TI - [Clarify the concepts and optimize psychiatry resources]. PMID- 26371486 TI - [Joint guidelines for spirometry needed]. PMID- 26371487 TI - [In Process Citation]. PMID- 26371488 TI - [In Process Citation]. PMID- 26371489 TI - [The inevitable fallibility--and how we approach infallibility]. PMID- 26371491 TI - [C--and then do]. PMID- 26371490 TI - [The refugee crisis engage the Swedish Medical Association]. PMID- 26371492 TI - Structural and Electrochemical Study of Hierarchical LiNi(1/3)Co(1/3)Mn(1/3)O2 Cathode Material for Lithium-Ion Batteries. AB - In this study, a facile nanoetching-template route is developed to synthesize porous nanomicrohierarchical LiNi1/3Co1/3Mn1/3O2 microspheres with diameters below 1.5 MUm, using porous CoMnO3 binary oxide microspheres as the template. The unique morphology of CoMnO3 template originates from the contraction effect during the oxidative decomposition of Ca0.2Mn0.4Co0.4CO3 precursors and is further improved by selectively removing calcium carbonate with a nanoetching process after calcination. The as-synthesized LiNi1/3Co1/3Mn1/3O2 microsphere, composed of numerous primary particles and pores with size of dozens of nanometers, illustrates a well-assembled porous nanomicrohierarchical structure. When used as the cathode material for lithium-ion batteries, the as-synthesized microspheres exhibit remarkably enhanced electrochemical performances with higher capacity, excellent cycling stability, and better rate capability, compared with the bulk counterpart. Specifically, hierarchical LiNi1/3Co1/3Mn1/3O2 achieves a high discharge capacity of 159.6 mA h g(-1) at 0.2 C with 98.7% capacity retention after 75 cycles and 133.2 mA h g(-1) at 1 C with 90% capacity retention after 100 cycles. A high discharge capacity of 135.5 mA h g(-1) even at a high current of 750 mA g(-1) (5 C) is also achieved. The nanoetching-template method can provide a general approach to improve cycling stability and rate capability of high capacity cathode materials for lithium-ion batteries. PMID- 26371493 TI - Identity priming consistently affects perceptual fluency but only affects metamemory when primes are obvious. AB - Perceptual fluency manipulations influence metamemory judgments, with more fluently perceived information judged as more memorable. However, it is not always clear whether this influence is driven by actual experienced processing fluency or by beliefs about memory. The current study used an identity-priming paradigm-in which words are preceded by either matched (identical) or mismatched primes-to examine the 2 influences. Participants named and made judgments of learning (JOLs) for critical words and then completed a memory test. In Experiment 1, we briefly presented the primes and found a priming effect on naming latencies but not on JOLs. In Experiment 2, we presented the primes for longer durations and, again, found an effect on naming in addition to an effect on JOLs. A mediation analysis revealed that naming latencies did not account for the prime-JOL relationship. This pattern of results demonstrated a manipulation of perceptual fluency that influenced JOLs only when belief-based information was readily available. PMID- 26371494 TI - Item strength influences source confidence and alters source memory zROC slopes. AB - Increasing the number of study trials creates a crossover pattern in source memory zROC slopes; that is, the slope is either below or above 1 depending on which source receives stronger learning. This pattern can be produced if additional learning affects memory processes such as the relative contribution of recollection and familiarity to source performance. However, the pattern can also be produced by decision processes if participants are more willing to make high confidence source judgments when they are more confident that the test item was studied. We explored the role of memory and decision processes by comparing performance across 3 conditions: (a) words seen once with a male or female face (no repetition), (b) words seen once with a face after being presented twice with a picture of either a bird or a fish (different-source repetition), and (c) words seen 3 times with the same face (same-source repetition). zROC functions for the male-female decision showed that different-source repetition produced the same crossover effect as same-source repetition. This pattern was predicted by the decision process account, because it assumes that increasing item memory affects source confidence ratings even if source memory is not improved. Also supporting this account, we found a strong positive relationship between recognition confidence and source confidence even when analyses were limited to items that were attributed to the incorrect source or items that were not studied in either source. PMID- 26371495 TI - A shape-based account for holistic face processing. AB - Faces are processed holistically, so selective attention to 1 face part without any influence of the others often fails. In this study, 3 experiments investigated what type of facial information (shape or surface) underlies holistic face processing and whether generalization of holistic processing to nonexperienced faces requires extensive discrimination experience. Results show that facial shape information alone is sufficient to elicit the composite face effect (CFE), 1 of the most convincing demonstrations of holistic processing, whereas facial surface information is unnecessary (Experiment 1). The CFE is eliminated when faces differ only in surface but not shape information, suggesting that variation of facial shape information is necessary to observe holistic face processing (Experiment 2). Removing 3-dimensional (3D) facial shape information also eliminates the CFE, indicating the necessity of 3D shape information for holistic face processing (Experiment 3). Moreover, participants show similar holistic processing for faces with and without extensive discrimination experience (i.e., own- and other-race faces), suggesting that generalization of holistic processing to nonexperienced faces requires facial shape information, but does not necessarily require further individuation experience. These results provide compelling evidence that facial shape information underlies holistic face processing. This shape-based account not only offers a consistent explanation for previous studies of holistic face processing, but also suggests a new ground-in addition to expertise-for the generalization of holistic processing to different types of faces and to nonface objects. PMID- 26371496 TI - Individual differences in the processing of written sarcasm and metaphor: Evidence from eye movements. AB - The present study examined individual differences in the processing of different forms of figurative language. Sixty participants read sarcastic, metaphorical, and literal sentences embedded in story contexts while their eye movements were recorded, and responded to a text memory and an inference question after each story. Individual differences in working memory capacity (WMC), need for cognition (NFC), and cognitive-affective processing were measured. The results showed that the processing of metaphors was characterized by slow-down during first-pass reading of the utterances, whereas sarcasm produced mainly delayed effects in the eye movement records. Sarcastic utterances were also harder to comprehend than literal or metaphorical utterances as indicated by poorer performance in responses to inference questions. Individual differences in general cognitive factors (WMC and NFC) were related to the processing of metaphors, whereas individual differences in both general cognitive factors (WMC) as well as processing of emotional information were related to the processing of sarcasm. The results indicate that different forms of figurative language pose different cognitive demands to the reader, and show that reader characteristics play a prominent role in figurative language comprehension. PMID- 26371497 TI - Daydreaming style moderates the relation between working memory and mind wandering: Integrating two hypotheses. AB - Mind wandering-mentation unrelated to one's current activity and surroundings-is a ubiquitous phenomenon, but seemingly competing ideas have been proposed regarding its relation to executive cognitive processes. The control-failure hypothesis postulates that executive processes prevent mind wandering, whereas the global availability hypothesis proposes that mind wandering requires executive resources, and thus an excess of such resources enables mind wandering. Here, we examined whether these hypotheses could be reconciled by considering the moderating influence of daydreaming style. We expected that executive resources would be positively related to mind wandering in those who typically experience positive mind wandering mentation, but negatively related in those who typically experience negative mentation. One hundred eleven participants reported mind wandering over 4 days using experience sampling and completed the sustained attention to response task (SART), the symmetry span task, and the Stroop task. There was a significant interaction between working memory and negative, but not positive, daydreaming style on mind wandering: Working memory related positively to mind wandering in those with a low negative style, but negatively in those with a high negative style. In contrast, poor Stroop performance significantly predicted increased mind wandering, but only in those with a low positive style. SART responses did not predict mind wandering although the relation was suggestively enhanced as the difficulty of daily life activities increased, indicating that the SART is more generalizable to high-demanding than low demanding activities. These results suggest that the content and context of mind wandering episodes play important roles in the relation between executive processes and mind wandering. PMID- 26371498 TI - Fragile associations coexist with robust memories for precise details in long term memory. AB - What happens to memories as we forget? They might gradually lose fidelity, lose their associations (and thus be retrieved in response to the incorrect cues), or be completely lost. Typical long-term memory studies assess memory as a binary outcome (correct/incorrect), and cannot distinguish these different kinds of forgetting. Here we assess long-term memory for scalar information, thus allowing us to quantify how different sources of error diminish as we learn, and accumulate as we forget. We trained subjects on visual and verbal continuous quantities (the locations of objects and the distances between major cities, respectively), tested subjects after extended delays, and estimated whether recall errors arose due to imprecise estimates, misassociations, or complete forgetting. Although subjects quickly formed precise memories and retained them for a long time, they were slow to learn correct associations and quick to forget them. These results suggest that long-term recall is especially limited in its ability to form and retain associations. PMID- 26371499 TI - Phosphine control of the oxidative addition chemistry of tetrathiocins to palladium(0): characterization of mono-, di-, and hexanuclear palladium(II) dithiolate complexes. AB - The outcome of the oxidative addition reactions of bis(4',5'-dimethoxybenzo) 1,2,5,6-tetrathiocin to Pd2dba3 under microwave conditions is sensitive to the nature of the phosphine coreagent; the bidentate phosphines dppm, dppe, and dppf afford the mononuclear dithiolates (dmobdt)Pd(dppm) (4), (dmobdt)Pd(dppe) (2), and (dmobdt)Pd(dppf) (5), whereas more labile monodentate phosphines lead to aggregation; Ph3P afforded the dinuclear dithiolate (dmobdt)2Pd2(PPh3)2 (6), whereas (t)Bu3P generated the phosphine-free hexanuclear edge-capped octahedral complex Pd6(dmobdt)6 (7) [dmobdt = 4,5-dimethoxybenzenedithiolate, (MeO)2C6H2S2(2 )]. PMID- 26371500 TI - Changes in cigarette smoking after traumatic spinal cord injury. AB - OBJECTIVE: The objective of this study is to identify changes in the prevalence of cigarette smoking approximately 1 year after discharge from inpatient rehabilitation for spinal cord injury (SCI). METHOD: Self-report assessments were completed by 129 participants with SCI during initial inpatient rehabilitation and at an average follow-up of 489 days postinjury. RESULTS: The prevalence of cigarette smoking declined from 36.4% at the time of SCI onset to 18.8%, and was not significantly different from the general population at follow-up. CONCLUSIONS: Whereas the prevalence of cigarette smoking is elevated at SCI onset, there are significant decreases in the smoking rate over the first 16 months after onset, indicating significant behavioral change. PMID- 26371501 TI - Radiation-force-based estimation of acoustic attenuation using harmonic motion imaging (HMI) in phantoms and in vitro livers before and after HIFU ablation. AB - Acoustic attenuation represents the energy loss of the propagating wave through biological tissues and plays a significant role in both therapeutic and diagnostic ultrasound applications. Estimation of acoustic attenuation remains challenging but critical for tissue characterization. In this study, an attenuation estimation approach was developed using the radiation-force-based method of harmonic motion imaging (HMI). 2D tissue displacement maps were acquired by moving the transducer in a raster-scan format. A linear regression model was applied on the logarithm of the HMI displacements at different depths in order to estimate the acoustic attenuation. Commercially available phantoms with known attenuations (n = 5) and in vitro canine livers (n = 3) were tested, as well as HIFU lesions in in vitro canine livers (n = 5). Results demonstrated that attenuations obtained from the phantoms showed a good correlation (R2 = 0.976) with the independently obtained values reported by the manufacturer with an estimation error (compared to the values independently measured) varying within the range of 15-35%. The estimated attenuation in the in vitro canine livers was equal to 0.32 +/- 0.03 dB cm(-1) MHz(-1), which is in good agreement with the existing literature. The attenuation in HIFU lesions was found to be higher (0.58 +/- 0.06 dB cm(-1) MHz(-1)) than that in normal tissues, also in agreement with the results from previous publications. Future potential applications of the proposed method include estimation of attenuation in pathological tissues before and after thermal ablation. PMID- 26371502 TI - Photoreducible Mercury Loss from Arctic Snow Is Influenced by Temperature and Snow Age. AB - Mercury (Hg) is an important environmental contaminant, due to its neurotoxicity and ability to bioaccumulate. The Arctic is a mercury-sensitive region, where organisms can accumulate high Hg concentrations. Snowpack mercury photoredox reactions may control how much Hg is transported with melting Arctic snow. This work aimed to (1) determine the significance of temperature combined with UV irradiation intensity and snow age on Hg(0) flux from Arctic snow and (2) elucidate the effect of temperature on snowpack Hg photoreduction kinetics. Using a Teflon flux chamber, snow temperature, UV irradiation, and snow age were found to significantly influence Hg(0) flux from Arctic snow. Cross-correlation analysis results suggest that UV radiation has a direct effect on Hg(0)flux, while temperature may indirectly influence flux. Laboratory experiments determined that temperature influenced Hg photoreduction kinetics when snow approached the melting point (>-2 degrees C), where the pseudo-first-order reduction rate constant, k, decreased twofold, and the photoreduced Hg amount, Hg(II)red, increased 10-fold. This suggests that temperature influences Hg photoreduction kinetics indirectly, likely by altering the solid:liquid water ratio. These results imply that large mass transfers of Hg from snow to air may take place during the Arctic snowmelt period, altering photoreducible Hg retention and transport with snow meltwater. PMID- 26371503 TI - Synthesis of Pyrano[3,2-c]pyrazol-7(1H)-one Derivatives by Tandem Cyclization of 2-Diazo-3,5-dioxo-6-ynoates (Ynones). AB - The construct of the core of pyrano[3,2-c]pyrazol-7(1H)-one derivatives is realized. The key step includes a tandem cyclization, namely, a metal-free cascade 6-pi electrocyclic ring closure-Michael reaction of 2-diazo-3,5-dioxo-6 ynoates (ynones). The cascade reaction cleanly generated the desired products in excellent yields under mild conditions. PMID- 26371504 TI - LC-MS- and (1)H NMR Spectroscopy-Guided Identification of Antifungal Diterpenoids from Sagittaria latifolia. AB - Antifungal screening of small-molecule natural product libraries showed that a column fraction (CF) derived from the plant extract of Sagittaria latifolia was active against the fungal pathogen Cryptococcus neoformans. Dereplication analysis by liquid chromatography-mass spectrometry (LC-MS) and proton nuclear magnetic resonance spectroscopy ((1)H NMR) indicated the presence of new compounds in this CF. Subsequent fractionation of the plant extract resulted in the identification of two new isopimaradiene-type diterpenoids, 1 and 2. The structures of 1 and 2 were determined by chemical methods and spectroscopic analysis as isopimara-7,15-dien-19-ol 19-O-alpha-l-arabinofuranoside and isopimara-7,15-dien-19-ol 19-O-alpha-l-(5'-acetoxy)arabinofuranoside, respectively. Compound 1 exhibited IC50 values of 3.7 and 1.8 MUg/mL, respectively, against C. neoformans and C. gattii. Its aglycone, isopimara-7,15 dien-19-ol (3), resulting from acid hydrolysis of 1, was also active against the two fungal pathogens, with IC50 values of 9.2 and 6.8 MUg/mL, respectively. This study demonstrates that utilization of the combined LC-MS and (1)H NMR analytical tools is an improved chemical screening approach for hit prioritization in natural product drug discovery. PMID- 26371505 TI - History of postpartum depression and the odds of maternal corporal punishment. AB - INTRODUCTION: Corporal punishment is closely related to physical abuse of children and is associated with several negative characteristics and experiences in children and youths. This study examined the relative unique contribution of 6 variables (social support, socioeconomic status, depression, self-efficacy, knowledge of child development, and history of postpartum depression) to maternal corporal punishment of children. METHOD: A sample of 76 mothers was dichotomized into those who never spanked or hit with an object and those who have spanked or hit with an object. The mothers were recruited from a community mental health agency, an urban community center, and a court of common pleas. The measures in the present study were administered prior to mothers' participation in a parent training program. Mothers referred by the court of common pleas were mandated to participate in the parent training program, and the mothers from the community mental health agency and the urban community center volunteered to participate in the parent training program. However, all participants voluntarily completed the research measures. RESULTS: Binary logistic regression identified postpartum depression as the only variable to significantly increase the odds of corporal punishment (odds ratio = 6.307, 95% confidence interval = 1.098-36.214, p = .039). DISCUSSION: The findings demonstrate increased odds of corporal punishment among a high-risk sample of women with postpartum depression. The generalizability of these findings may be limited to low socioeconomic class and White and African American mothers enrolled in parent-training programs. (PsycINFO Database Record PMID- 26371507 TI - Probing the stress and depression circuits with a disease gene. AB - Selectively deleting a gene that has been linked to depression from specific neurons in mice sheds new light on a neural circuit that controls stress-induced depressive behaviors. PMID- 26371506 TI - Structured illumination with particle averaging reveals novel roles for yeast centrosome components during duplication. AB - Duplication of the yeast centrosome (called the spindle pole body, SPB) is thought to occur through a series of discrete steps that culminate in insertion of the new SPB into the nuclear envelope (NE). To better understand this process, we developed a novel two-color structured illumination microscopy with single particle averaging (SPA-SIM) approach to study the localization of all 18 SPB components during duplication using endogenously expressed fluorescent protein derivatives. The increased resolution and quantitative intensity information obtained using this method allowed us to demonstrate that SPB duplication begins by formation of an asymmetric Sfi1 filament at mitotic exit followed by Mps1 dependent assembly of a Spc29- and Spc42-dependent complex at its tip. Our observation that proteins involved in membrane insertion, such as Mps2, Bbp1, and Ndc1, also accumulate at the new SPB early in duplication suggests that SPB assembly and NE insertion are coupled events during SPB formation in wild-type cells. PMID- 26371508 TI - The splicing regulators Esrp1 and Esrp2 direct an epithelial splicing program essential for mammalian development. AB - Tissue- and cell-type-specific regulators of alternative splicing (AS) are essential components of posttranscriptional gene regulation, necessary for normal cellular function, patterning, and development. Mice with ablation of Epithelial splicing regulatory protein (Esrp1) develop cleft lip and palate. Loss of both Esrp1 and its paralog Esrp2 results in widespread developmental defects with broad implications to human disease. Deletion of the Esrps in the epidermis revealed their requirement for establishing a proper skin barrier, a primary function of epithelial cells comprising the epidermis. We profiled the global Esrp-mediated splicing regulatory program in epidermis, which revealed large scale programs of epithelial cell-type-specific splicing required for epithelial cell functions. These mice represent a valuable model for evaluating the essential role for AS in development and function of epithelial cells, which play essential roles in tissue homeostasis in numerous organs, and provide a genetic tool to evaluate important functional properties of epithelial-specific splice variants in vivo. PMID- 26371509 TI - Phosphodiesterase 4D acts downstream of Neuropilin to control Hedgehog signal transduction and the growth of medulloblastoma. AB - Alterations in Hedgehog (Hh) signaling lead to birth defects and cancers including medulloblastoma, the most common pediatric brain tumor. Although inhibitors targeting the membrane protein Smoothened suppress Hh signaling, acquired drug resistance and tumor relapse call for additional therapeutic targets. Here we show that phosphodiesterase 4D (PDE4D) acts downstream of Neuropilins to control Hh transduction and medulloblastoma growth. PDE4D interacts directly with Neuropilins, positive regulators of Hh pathway. The Neuropilin ligand Semaphorin3 enhances this interaction, promoting PDE4D translocation to the plasma membrane and cAMP degradation. The consequent inhibition of protein kinase A (PKA) enhances Hh transduction. In the developing cerebellum, genetic removal of Neuropilins reduces Hh signaling activity and suppresses proliferation of granule neuron precursors. In mouse medulloblastoma allografts, PDE4D inhibitors suppress Hh transduction and inhibit tumor growth. Our findings reveal a new regulatory mechanism of Hh transduction, and highlight PDE4D as a promising target to treat Hh-related tumors. PMID- 26371511 TI - Price-Focused Analysis of Commercially Available Building Blocks for Combinatorial Library Synthesis. AB - Combinatorial libraries are synthesized by combining smaller reagents (building blocks), the price of which is an important component of the total costs associated with the synthetic exercise. A significant portion of commercially available reagents are too expensive for large scale work. In this study, 13 commonly used reagent classes in combinatorial library synthesis (primary and secondary amines, carboxylic acids, alcohols, ketones, aldehydes, boronic acids, acyl halides, sulfonyl chlorides, isocyanates, isothiocyanates, azides and chloroformates) were analyzed with respect to the cost, physicochemical properties (molecular weight and calculated logP), chemical diversity, and 3D likeness using a large data set. The results define the chemical space accessible under a constraint of limited financial resources. PMID- 26371510 TI - Layer 2/3 pyramidal cells in the medial prefrontal cortex moderate stress induced depressive behaviors. AB - Major depressive disorder (MDD) is a prevalent illness that can be precipitated by acute or chronic stress. Studies of patients with Wolfram syndrome and carriers have identified Wfs1 mutations as causative for MDD. The medial prefrontal cortex (mPFC) is known to be involved in depression and behavioral resilience, although the cell types and circuits in the mPFC that moderate depressive behaviors in response to stress have not been determined. Here, we report that deletion of Wfs1 from layer 2/3 pyramidal cells impairs the ability of the mPFC to suppress stress-induced depressive behaviors, and results in hyperactivation of the hypothalamic-pituitary-adrenal axis and altered accumulation of important growth and neurotrophic factors. Our data identify superficial layer 2/3 pyramidal cells as critical for moderation of stress in the context of depressive behaviors and suggest that dysfunction in these cells may contribute to the clinical relationship between stress and depression. PMID- 26371512 TI - Functionalized gold nanoparticles improve afatinib delivery into cancer cells. AB - OBJECTIVES: A drug delivery system based on colloidal pegylated gold nanoparticles (PEGAuNPs) conjugated with the tyrosine kinase inhibitor afatinib was designed and tested for enhancing the drug activity against pancreatic and NSCLC cells. METHODS: PEGAuNPs were synthesized and characterized physicochemically. Confocal imaging was performed to evaluate the nanoparticle (NP) internalization in cancer cells. For cell-cycle distribution analysis, conjugated NPs and afatinib alone were incubated with cells and alterations on the cell-cycle profile subsequently analyzed by total DNA staining. Cancer cell survival and growth inhibition following incubation with afatinib and PEGAuNPs afatinib (concentrations between 0.007 and 0.500 uM afatinib) were evaluated. RESULTS: A higher cellular uptake of PEGAuNPs was observed by cancer cells. Our data suggest an efficient conjugation of PEGAuNPs with the drug, enhancing the afatinib activity in comparison with afatinib alone. In fact, IC50 and GI50 results obtained show that the PEGAuNPs-afatinib conjugate is ca. 5 and 20 times more potent than afatinib alone in S2-013 and A549 cell lines, respectively. CONCLUSIONS: Conjugating PEGAuNPs with afatinib is a promising antitumor delivery system for cancer therapy as it improves drug efficacy, allowing a reduction in drug dose used and minimizing possible toxicity-related side effects. PMID- 26371513 TI - Relationship between the cortisol levels in umbilical cord blood and neonatal RDS/TTN in twin pregnancies. AB - OBJECTIVE: Twin neonates have a higher risk of respiratory complications, such as respiratory distress syndrome (RDS) and transient tachypnea of the newborn (TTN), than singleton neonates. The purpose of this study was to evaluate the relationship between the cortisol levels in the umbilical cord and neonatal RDS/TTN in twin pregnancies. METHODS: We analyzed data obtained from 106 neonates (53 twin pairs), comprising 33 dichorionic twin (DCT) and 20 monochorionic twin (MCT) gestations. All infants were delivered via scheduled cesarean section without labor. We measured the cortisol levels in umbilical vein blood using enzyme-linked immunosorbent assay. RESULTS: The cortisol levels in the umbilical vein were significantly lower in the RDS/TTN group than in the no RDS/TTN group (p = 0.004). The umbilical cortisol levels in the TTN group were between the values observed in the RDS group and no RDS/TTN group. We subsequently analyzed the cut-off cortisol values for RDS/TTN and observed higher accuracy in the DCTs than in the MCTs. CONCLUSIONS: Neonates who develop RDS/TTN have significantly lower cortisol levels in the umbilical cord at birth than no RDS/TTN neonates in twin pregnancies. When applying these data in clinical practice, physicians should pay attention to differences based on chorionicity. PMID- 26371514 TI - Shorter the cervix, more difficult the placenta percreta operations. AB - BACKGROUND: To determine the impact of cervical length (CL) on the clinical outcome of patients undergoing peripartum hysterectomy due to placenta previa/percreta. OBJECTIVE: To assess the association of CL with clinical outcomes in such patients. METHODS: We analyzed the data of patients who were diagnosed with anterior placenta previa/percreta prenatally and subsequently underwent peripartum hysterectomy at our tertiary care institution between 2004 and 2014. The sonographic images and measurements of CL were obtained from prospectively collected database. The duration of operation, units of blood products transfused, and length of stay in the hospital were recorded. Patients were stratified according to CL, and receiver-operating characteristics curves were used to determine the cut-off length for identification of patients at high risk of intra-operative difficulty. RESULTS: Sixty-one patients were included in this study. Number of packages of ES were correlated with the the duration of operation (r = 0.666, p < 0.001) and the CL (-0.793, p < 0.001). Number of packages of fresh frozen plasma was significantly correlated with the CL (-0.642, p < 0.001) and the duration of operation (r = 0.606, p < 0.001). Gestational age (AUC = 0.683, p = 0.014) and the CL (AUC = 0.980, p < 0.014) were significant predictors for the number of ES transfused > 4 packages. The cut-off value of four packages was determined according to the median level of packages transfused. Optimal cut-off value for the CL to predict transfusion <= 4 packages was 20.5 with 93% sensitivity and the 99% specificity. CONCLUSIONS: Short cervix appears to be a cause of difficulty in placenta previa/percreta operations. CL may also help in determining the timing of delivery in placenta percreta patients. PMID- 26371516 TI - Minimally invasive procedures for the management of vertebral bone pain due to cancer: The EAPC recommendations. AB - BACKGROUND: Image-guided percutaneous ablation methods have proved effective for treatment of benign bone tumors and for palliation of metastases involving the bone. However, the role of these techniques is controversial and has to be better defined in the setting of palliative care. METHODS: A systematic review of the existing data regarding minimally invasive techniques for the pain management of vertebral bone metastases was performed by experts of the European Palliative Care Research Network. RESULTS: Only five papers were taken into consideration after performing rigorous screening according to inclusion and exclusion criteria (low number of patients, retrospective series, proceedings). DISCUSSION: According to the present data a recommendation should be made to perform kiphoplasty in patients with vertebral tumors or metastases. However, the strength of this recommendation was based on one randomized controlled study. Several weaknesses and low quality of study design were observed with other techniques. CONCLUSION: Further randomized controlled trials are required to improve the strength of evidence available to suggest these procedures on large scale. Until then, the balance of evidence favors the use of these procedures in a small select cohort of patients with severe and disabling back pain refractory to medical therapy. PMID- 26371515 TI - Splicing Factor Prp8 Interacts With NES(AR) and Regulates Androgen Receptor in Prostate Cancer Cells. AB - Androgen receptor (AR) plays a pivotal role in the development of primary as well as advanced castration-resistant prostate cancer. Previous work in our lab identified a novel nuclear export signal (NES) (NES(AR)) in AR ligand-binding domain essential for AR nucleocytoplasmic trafficking. By characterizing the localization of green fluorescence protein (GFP)-tagged NES(AR), we designed and executed a yeast mutagenesis screen and isolated 7 yeast mutants that failed to display the NES(AR) export function. One of those mutants was identified as the splicing factor pre-mRNA processing factor 8 (Prp8). We further showed that Prp8 could regulate NES(AR) function using short hairpin RNA knockdown of Prp8 coupled with a rapamycin export assay in mammalian cells and knockdown of Prp8 could induce nuclear accumulation of GFP-tagged AR in PC3 cells. Prp8 expression was decreased in castration-resistant LuCaP35 xenograft tumors as compared with androgen-sensitive xenografts. Laser capture microdissection and quantitative PCR showed Prp8 mRNA levels were decreased in human prostate cancer specimens with high Gleason scores. In prostate cancer cells, coimmunoprecipitation and deletion mutagenesis revealed a physical interaction between Prp8 and AR mainly mediated by NES(AR). Luciferase assay with prostate specific antigen promoter-driven reporter demonstrated that Prp8 regulated AR transcription activity in prostate cancer cells. Interestingly, Prp8 knockdown also increased polyubiquitination of endogenous AR. This may be 1 possible mechanism by which it modulates AR activity. These results show that Prp8 is a novel AR cofactor that interacts with NES(AR) and regulates AR function in prostate cancer cells. PMID- 26371517 TI - A dysphoric's TALE: The relationship between the self-reported functions of autobiographical memory and symptoms of depression. AB - Autobiographical memory (AM) is believed to serve self, social and directive functions; however, little is known regarding how this triad of functions operates in depression. Using the Thinking About Life Experiences questionnaire [Bluck, S., & Alea, N. (2011). Crafting the TALE: Construction of a measure to assess the functions of autobiographical remembering. Memory, 19, 470-486.; Bluck, S., Alea, N., Habermas, T., & Rubin, D. C. (2005). A TALE of three functions: The self-reported uses of autobiographical memory. Social Cognition, 23, 91-117.], two studies explored the relationship between depressive symptomology and the self-reported frequency and usefulness of AMs for self, social and directive purposes. Study 1 revealed that thinking more frequently but talking less frequently about past life events was significantly associated with higher depression scores. Recalling past events more frequently to maintain self continuity was also significantly associated with higher depressive symptomology. However, results from Study 2 indicated that higher levels of depression were also significantly associated with less-frequent useful recollections of past life events for self-continuity purposes. Taken together, the findings suggest atypical utilisations of AM to serve self-continuity functions in depression and can be interpreted within the wider context of ruminative thought processes. PMID- 26371519 TI - Assistive technologies in reducing caregiver burden among informal caregivers of older adults: a systematic review. AB - AIM: The world population is rapidly ageing. As population age, the incidence of functional limitations increases, demanding higher levels of care from caregivers. Assistive technologies improve individuals' functioning, independence, well-being and quality of life. By increasing independence of older adults, assistive technologies decrease workloads required from informal caregivers. This review investigates, evaluates, and synthesises existing findings to examine whether and how assistive technologies reduce caregiver burden. METHODS: Databases searched included MEDLINE, EMBASE, Scopus, and Cochrane Library. Three groups of keywords were combined: those relating to assistive technology, caregiver burden, and older adults. RESULTS: Two theories emerged from the analysis of study results. Caregivers reported that assistive technologies decrease caregiver burden. However, caregivers had concerns that assistive technologies could add to caregiver burden, highlighting the limitations of assistive technology. CONCLUSIONS: As suggested by a majority of the studies in this review, assistive technologies contribute to reducing caregiver burden among caregivers of older adults. Assistive technologies assisted caregivers by reducing time, levels of assistance and energy put towards caregiving, anxiety and fear, task difficulty, safety risk particularly for activities requiring physical assistance and increasing the independence of the users. Further research is required to better understand limitations of assistive technologies. Implications for Rehabilitation Support for informal caregivers of older adults need more attention and recognition. Assistive technologies can reduce caregiver burden among informal caregivers of older adults. Further research is required to better understand the effectiveness of assistive technologies in reducing caregiver burden as well as limitations and barriers associated with using assistive technologies. PMID- 26371518 TI - Efficacy and safety of fixed dose combination of atorvastatin and hydroxychloroquine: a randomized, double-blind comparison with atorvastatin alone among Indian patients with dyslipidemia. AB - OBJECTIVE: To evaluate the efficacy and safety of atorvastatin + hydroxychloroquine fixed-dose combination tablets in comparison with atorvastatin alone in treatment of dyslipidemia. METHODS: This double-blind, randomized, out patient study was conducted in 328 patients with primary dyslipidemia having low density lipoprotein cholesterol (LDL-C) >= 130 mg/dL (3.37 mmol/L) to <= 250 mg/dL (6.48 mmol/L) and triglycerides <= 400 mg/dL (4.52 mmol/L). Eligible patients were randomized to receive either atorvastatin 10 mg (n = 167) or atorvastatin 10 mg + hydroxychloroquine 200 mg (n = 161) for 24 weeks. CLINICAL TRIAL REGISTRATION: CTRI/2010/091/006138. MAIN OUTCOME MEASURES: To compare percentage change in LDL-C, total cholesterol (TC), triglycerides, high-density lipoprotein cholesterol (HDL-C) and non-high-density lipoprotein cholesterol (non HDL-C) from baseline to Week 12 and Week 24 between groups. To compare mean change in glycated hemoglobin (HbA1c), fasting blood glucose (FBG), high sensitivity C-reactive protein (Hs-CRP), and percentage of patients achieving lipid goals at Week 12 and Week 24. RESULTS: At Week 24, percentage reduction in LDL-C (-32.52 [-36.13 to -28.91] vs -39.54 [-43.25 to -35.83]; p = 0.008), TC ( 24.41 [-27.10 to -21.72] vs -29.30 [-32.07 to -26.54]; p = 0.013), and non-HDL-C (-30.37 [-33.71 to -27.04] vs -36.76 [-40.18 to -33.33]; p = 0.009) was significantly greater in combination treated patients. Both the treatments showed a significant reduction in triglycerides at Week 24 from baseline, however, this reduction was not statistically significantly different between treatment groups. No significant change in HDL-C was observed in patients from both the treatment groups. At Week 24, change in HbA1c (0.22 [0.07 to 0.37] vs -0.13 [-0.28 to 0.03]; p = 0.002) and FBG was also statistically significant in favor of combination therapy (0.37 [0.07 to 0.67] vs -0.29 [-0.59 to 0.03]; p = 0.003), whereas no statistically significant difference was observed in change in Hs-CRP (p = 0.310). Significantly more patients from the combination group achieved LDL C and TC goals. Exploratory analysis in patients with pre-diabetes showed development of diabetes in 8 patients (15.09%) from the monotherapy group and 1 patient (1.96%) from the combination group (p = 0.034). Study medications were generally safe and well tolerated. CONCLUSION: Based on study results and widely reported pleiotropic benefits, hydroxychloroquine could emerge as a potential drug for combination with statins for treatment of dyslipidemia. Long duration studies with larger sample sizes are required to further explore the role of hydroxychloroquine as adjunct to statins in reducing risk of cardiovascular events and prevention of statin-induced diabetes. PMID- 26371520 TI - Impact of Older Adults' Neighborhood Perceptions on Walking Behavior. AB - Built environment features can have varying impacts on user behavior depending on the perceptions of the opportunities and obstacles that the environments create. This study systematically evaluated the relationship between neighborhood perceptions and the specific types of self-reported walking behavior for 121 older adults who resided in urban, suburban, or rural neighborhoods. Perceptions of street connectivity, crime and traffic safety, and overall satisfaction were associated with specific types of walking behaviors, and the strength of the relationships differed by neighborhood type. Sociodemographic variables such as age and sex were associated with certain types and amounts of older adults' walking behaviors both across and within each neighborhood type. The results of this study support the importance of perceived street connectivity regardless of neighborhood type and perceived crime safety in rural neighborhoods to impact the walking behavior among older adults. PMID- 26371521 TI - Heritability and Temporal Stability of Ambulatory Autonomic Stress Reactivity in Unstructured 24-Hour Recordings. AB - OBJECTIVE: Measurements of ambulatory autonomic reactivity can help with our understanding of the long-term health consequences of exposure to psychosocial stress in real-life settings. METHODS: In this study, unstructured 24-hour ambulatory recordings of cardiac parasympathetic and sympathetic control were obtained in 1288 twins and siblings, spanning both work time and leisure time. These data were used to define two ambulatory baseline (sleep, leisure) and four stress conditions (wake, work, work_sitting, work_peak) from which six ambulatory stress reactivity measures were derived. The use of twin families allowed for estimation of heritability and testing for the amplification of existing or emergence of new genetic variance during stress compared with baseline conditions. RESULTS: Temporal stability of ambulatory reactivity was assessed in 62 participants and was moderate to high over a 3-year period (0.36 < r < 0.91). Depending on the definition of ambulatory reactivity used, significant heritability was found, ranging from 29% to 40% for heart rate, 34% to 47% for cardiac parasympathetic control (indexed as respiratory sinus arrhythmia), and 10% to 19% for cardiac sympathetic control (indexed as the preejection period). Heritability of ambulatory reactivity was largely due to newly emerging genetic variance during stress compared with periods of rest. Interestingly, reactivity to short standardized stressors was poorly correlated with the ambulatory reactivity measures implying poor laboratory-real-life correspondence. CONCLUSIONS: Ambulatory autonomic reactivity extracted from an unstructured real life setting shows reliable, stable, and heritable individual differences. Real life situations uncover a new and different genetic variation compared with that seen in resting baseline conditions, including sleep. PMID- 26371522 TI - ACR Appropriateness Criteria(r) Local Excision in Early Stage Rectal Cancer. AB - Low anterior resection or abdominoperineal resection are considered standard treatments for early rectal cancer but may be associated with morbidity in selected patients who are candidates for early distal lesions amenable to local excision (LE). The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. The panel recognizes the importance of accurate staging to identify patients who may be candidates for a LE approach. Patients who may be candidates for LE alone include those with small, low-lying T1 tumors, without adverse pathologic features. Several surgical approaches can be utilized for LE however none include lymph node evaluation. Adjuvant radiation+/-chemotherapy may be warranted depending on the risk of nodal metastases. Patients with high-risk T1 tumors, T2 tumors not amenable to radical surgery may also benefit from adjuvant treatment; however, patients with positive margins or T3 lesions should be offered abdominoperineal resection or low anterior resection. Neoadjuvant radiation+/-chemotherapy followed by LE in higher risk patients results in excellent local control, but it is not clear if this approach reduces recurrence rates over surgery alone. PMID- 26371523 TI - Ambulatory and home blood pressure monitoring in people with chronic kidney disease. Time to abandon clinic blood pressure measurements? AB - PURPOSE OF REVIEW: There is currently much interest in the usefulness of out-of office blood pressure (BP) for the diagnosis and the management of hypertension in patients with chronic kidney disease (CKD). This is not to suggest that office BP should be disregarded and we will take the opportunity to stress how it could be improved. RECENT FINDINGS: Arterial hypertension constitutes a very relevant cardiovascular and renal risk factor in patients with CKD. To assess this risk, the best tool is ambulatory BP monitoring (ABPM), as it allows the detection of masked hypertension, masked untreated hypertension (MUCH) and nondipping pattern, conditions known to be associated with target organ damage that further contributes to increased risk to the patient. Home BP monitoring (HBPM) cannot fully substitute for ABPM because of the absence of BP data during the night. Despite this, there are good reasons to use HBPM systematically in patients with CKD during long-term follow-up. SUMMARY: In the individual patient office, BP may significantly differ from out-of-office measurements. This shortcoming can be attenuated by repeated measurement at every visit, but even if office BP is considered normal, it is still highly desirable to obtain out-of-office data. PMID- 26371524 TI - Individualizing the dialysate calcium concentration. AB - PURPOSE OF REVIEW: The optimal dialysate calcium concentration (DCC) in hemodialysis patients is still debated. Strategies have varied over time due to developments in the treatments available for mineral metabolism disorders and our increasing knowledge of bone and vascular diseases. International recommendations [Kidney Disease Outcomes Quality Initiative (KDIGO) and European Best Practice Guidelines] urge for DCC individualization in order to meet the patient's specific needs whenever possible. In this review, we aim to discuss the pros and cons of individualizing the DCC in hemodialysis patients. RECENT FINDINGS: Different regions of the world have various strategies with respect to DCCs. Decreasing the DCC slightly reduces calcemia, but mainly stimulates parathyroid hormone secretion and bone turnover. Conversely, increasing the DCC increases calcemia slightly and reduces parathyroid hormone secretion and bone turnover markedly. Furthermore, higher DCCs favor hemodynamic stability and can prevent ventricular arrhythmias. The impact of DCC individualization on survival rate or cardiovascular calcification progression has not been evaluated. SUMMARY: Individualizing DCC appears to be useful but requires time, a clear defined strategy, and close biological monitoring. Even though some studies have shown that using individualized DCCs of 1.25 or 1.75 mmol/l is not harmful, the real benefits of this strategy need to be assessed in a large, multicentric trial. PMID- 26371526 TI - Medical management of chronic kidney disease in the renal transplant recipient. AB - PURPOSE OF REVIEW: An updated overview of the state-of-the-art approaches to the care of chronic kidney disease-related issues in renal transplant recipients. RECENT FINDINGS: These include the impact of immunosuppression therapy on kidney function, the management of cardiovascular risk, metabolic bone disease, and hematologic complications, with a focus on the care of the patient with a failing allograft. SUMMARY: A kidney transplant improves patient morbidity and mortality, but almost all transplant patients continue to have morbidity related to chronic kidney disease. It is increasingly clear that the provision of adequate immunosuppression is important to preserve allograft function. Recent studies have lent support to current guidelines for the management of cardiovascular risk factors in transplant patients. New data regarding the management of metabolic bone disease are sparse. Erythropoietin replacement may improve outcomes in transplant recipients, but the optimal target hemoglobin level is not known. Cessation of immunosuppression in the failed allograft carries the risk of rejection and allosensitization. New evidence suggests that nephrectomy may reduce mortality in patients with a failed allograft, but likely enhances sensitization in the patient awaiting retransplantation. PMID- 26371525 TI - Rapid ultrafiltration rates and outcomes among hemodialysis patients: re examining the evidence base. AB - PURPOSE OF REVIEW: This review critically summarizes the evidence linking ultrafiltration rates to adverse outcomes among hemodialysis patients and provides research recommendations to address knowledge gaps. RECENT FINDINGS: Growing evidence suggests that fluid-related factors play important roles in hemodialysis patient outcomes. Ultrafiltration rate - the rate of fluid removal during hemodialysis - is one such factor. Existing observational data suggest a robust association between greater ultrafiltration rates and adverse cardiovascular outcomes, and such findings are supported by plausible physiologic rationale. Potential mechanistic pathways include ultrafiltration-related ischemia to the heart, brain, and gut, and volume overload-precipitated cardiac stress from reactive measures to ultrafiltration-induced hemodynamic instability. Inter-relationships among ultrafiltration rates and other fluid measures, such as interdialytic weight gain and chronic volume expansion, render the specific role of ultrafiltration rates in adverse outcomes difficult to study. Randomized trials must be conducted to confirm epidemiologic findings and examine the effect of ultrafiltration rate reduction on clinical and patient-centered outcomes. SUMMARY: Compelling observational data demonstrate an association between more rapid ultrafiltration rates and adverse clinical outcomes. Before translating these findings into clinical practice, randomized trials are needed to verify observational data results and to identify effective strategies to mitigate ultrafiltration-related risk. PMID- 26371527 TI - Chronic kidney disease in older people - diagnosis, aetiology and consequences. AB - PURPOSE OF REVIEW: The prevalence of chronic kidney disease (CKD) steeply rises with age but there is controversy regarding the diagnosis and clinical significance of CKD in older people. This article reviews recent advances in our understanding with respect to the diagnosis, aetiology and adverse outcomes associated with CKD in older people. RECENT FINDINGS: Comparisons with measured glomerular filtration rate in a cohort of older people found that the Chronic Kidney Disease Epidemiology Collaboration equation using creatinine and cystatin C performs at least as well as other equations developed to estimate glomerular filtration rate in older populations. Several studies have identified modifiable risk factors in earlier life that are associated with increased risk of developing CKD in later life, including blood pressure, biomarkers of cardiovascular disease and lower serum bicarbonate. Numerous studies have confirmed that CKD in older people is associated with an increased risk of multiple adverse outcomes including death, end-stage kidney disease, cardiovascular events, acute kidney injury, severe infections and cognitive decline. SUMMARY: CKD is associated with the same adverse outcomes in older people as younger people. Further studies are required to develop interventions to reduce the incidence of CKD in older people and improve the associated adverse outcomes. PMID- 26371528 TI - The perils of immunosuppression minimization: lessons from protocol biopsies of renal allografts. AB - PURPOSE OF REVIEW: To emphasize the pathogenicity of subclinical cellular inflammation in renal transplant recipients, and its relation to poor graft outcomes and the development of de-novo donor-specific antibody (DSA). RECENT FINDINGS: Protocol biopsies have identified the gene signatures of innate and adaptive immunity in patients with minimal inflammation that correlate with the subsequent development of graft interstitial fibrosis, transplant glomerulopathy and antibody-mediated rejection. The risks of immunosuppression minimization, especially in HLA mismatched donor-recipient pairs, are highlighted. SUMMARY: The major cause of renal allograft loss is immunological and a contributor to this is the minimization of immunosuppression. The prevention of premature graft loss requires better matching of class II HLA antigens, the targets of de-novo DSA, and monitoring for subclinical inflammation rejection with protocol biopsies or urine chemokines. PMID- 26371529 TI - Multidisciplinary approach to calcific uremic arteriolopathy. AB - PURPOSE OF REVIEW: Calcific uremic arteriolopathy (CUA), as known as calciphylaxis, is a rare and poorly understood disease seen predominantly in end stage renal disease patients. A collaborative multidisciplinary approach to develop and implement treatment and prevention methods is described. RECENT FINDINGS: Overall, the scientific literature on CUA is largely restricted to case reports and case series. Recent reports indicate that the incidence of CUA may be on the rise and emphasize an association with vitamin K antagonist therapy, obesity, and diabetes mellitus. Serum calcium, phosphorous, and parathyroid hormone levels have been reported to be quite variable in patients with CUA and may reflect the heterogeneity of study designs. A multidisciplinary and multimodal approach that incorporates wound and pain management, sodium thiosulfate, optimization of mineral bone parameters, bisphosphonates, and avoidance of risk factors such as vitamin K antagonist has been advocated in the latest reports. Sodium thiosulfate although used frequently to treat CUA has unclear efficacy requiring further examination. SUMMARY: This review describes the recent literature in the field of CUA including its limitations. It provides a summary of a multidisciplinary approach to CUA management. PMID- 26371530 TI - The Human Movement System in Neurologic Physical Therapy. PMID- 26371531 TI - Effect of Developmental Binocular Vision Abnormalities on Visual Vertigo Symptoms and Treatment Outcome. AB - BACKGROUND AND PURPOSE: Customized vestibular rehabilitation incorporating optokinetic (OK) stimulation improves visual vertigo (VV) symptoms; however, the degree of improvement varies among individuals. Binocular vision abnormalities (misalignment of ocular axis, ie, strabismus) may be a potential risk factor. This study aimed to investigate the influence of binocular vision abnormalities on VV symptoms and treatment outcome. METHODS: Sixty subjects with refractory peripheral vestibular symptoms underwent an orthoptic assessment after being recruited for participation in an 8-week customized program incorporating OK training via a full-field visual environment rotator or video display, supervised or unsupervised. Treatment response was assessed at baseline and at 8 weeks with dynamic posturography, Functional Gait Assessment (FGA), and questionnaires for symptoms, symptom triggers, and psychological state. As no significant effect of OK training type was noted for any variables, data were combined and new groups identified on the basis of the absence or presence of a binocular vision abnormality. RESULTS: A total of 34 among 60 subjects consented to the orthoptic assessment, of whom 8 of the 34 had binocular vision abnormalities and 30 of the 34 subjects completed both the binocular function assessment and vestibular rehabilitation program. No significant between-group differences were noted at baseline. The only significant between-group difference was observed for pre /post-VV symptom change (P = 0.01), with significant improvements noted only for the group without binocular vision abnormalities (P < 0.0005). Common vestibular symptoms, posturography, and the FGA improved significantly for both groups (P < 0.05). DISCUSSION AND CONCLUSIONS: Binocular vision abnormalities may affect VV symptom improvement. These findings may have important implications for the management of subjects with refractory vestibular symptoms.Video Abstract available for insights from the authors regarding clinical implication of the study findings (see Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A115). PMID- 26371532 TI - Predicting Heart Rate at the Ventilatory Threshold for Aerobic Exercise Prescription in Persons With Chronic Stroke. AB - BACKGROUND AND PURPOSE: Treadmill aerobic exercise improves gait, aerobic capacity, and cardiovascular health after stroke, but a lack of specificity in current guidelines could lead to underdosing or overdosing of aerobic intensity. The ventilatory threshold (VT) has been recommended as an optimal, specific starting point for continuous aerobic exercise. However, VT measurement is not available in clinical stroke settings. Therefore, the purpose of this study was to identify an accurate method to predict heart rate at the VT (HRVT) for use as a surrogate for VT. METHODS: A cross-sectional design was employed. Using symptom limited graded exercise test (GXT) data from 17 subjects more than 6 months poststroke, prediction methods for HRVT were derived by traditional target HR calculations (percentage of HRpeak achieved during GXT, percentage of peak HR reserve [HRRpeak], percentage of age-predicted maximal HR, and percentage of age predicted maximal HR reserve) and by regression analysis. The validity of the prediction methods was then tested among 8 additional subjects. RESULTS: All prediction methods were validated by the second sample, so data were pooled to calculate refined prediction equations. HRVT was accurately predicted by 80% HRpeak (R, 0.62; standard deviation of error [SDerror], 7 bpm), 62% HRRpeak (R, 0.66; SDerror, 7 bpm), and regression models that included HRpeak (R, 0.62-0.75; SDerror, 5-6 bpm). DISCUSSION AND CONCLUSIONS: Derived regression equations, 80% HRpeak and 62% HRRpeak, provide a specific target intensity for initial aerobic exercise prescription that should minimize underdosing and overdosing for persons with chronic stroke. The specificity of these methods may lead to more efficient and effective treatment for poststroke deconditioning.Video Abstract available for more insights from the authors (see Supplemental Digital Content 1, http://links.lww.com/JNPT/A114). PMID- 26371533 TI - Neurology Section 2015 Barnes and Leahy Promotion of Doctoral Studies (PODS) Awards. PMID- 26371534 TI - Kidney Transplantation: Multiparametric Functional Magnetic Resonance Imaging for Assessment of Renal Allograft Pathophysiology in Mice. AB - OBJECTIVES: The aims of this experimental study were to investigate renal allograft pathophysiology by multiparametric functional magnetic resonance imaging (MRI) and to directly correlate MRI parameters with renal histopathology in mouse models of allogenic and isogenic kidney transplantation (ktx). MATERIALS AND METHODS: Allograft rejection was induced by transplantation of C57BL/6 (B6) donor kidneys into BALB/c recipients (allogenic ktx). B6 mice that received B6 kidneys served as controls (isogenic ktx). Three weeks after ktx, MRI was performed using a 7-T small-animal scanner. Flow sensitive alternating inversion recovery echoplanar imaging arterial spin labeling, multiecho turbo spin echo, and diffusion-weighted imaging sequences were acquired. Maps of renal perfusion, T2 and T1 relaxation times, and apparent diffusion coefficients were calculated. Histological changes in the kidney were evaluated according to Banff criteria. Renal cell infiltrates and fibrosis were quantified by immunohistochemistry. Differences between groups were assessed using the Mann-Whitney U test, and the correlation of MRI parameters with renal histopathology was determined by Spearman correlation analysis. RESULTS: After allogenic, but not isogenic, ktx, animals developed acute allograft rejection. Allogenic grafts were infiltrated by macrophages and T-lymphocytes and exhibited marked renal fibrosis. Magnetic resonance imaging revealed stronger impairment of renal perfusion (56 +/- 7 vs 293 +/- 44 mL/[min * 100 g]; P < 0.01) and more pronounced increases in T2 (60.1 +/- 2.0 vs 45.7 +/- 1.2 milliseconds, P < 0.01) and T1 relaxation times (1938 +/- 53 vs 1350 +/- 27 milliseconds, P < 0.01) in allogenic than in isogenic kidneys. Apparent diffusion coefficient was reduced to 1.39 +/- 0.14 * 10(-3) mm2/s in kidneys with an acute rejection and was 1.83 +/- 0.05 * 10(-3) mm2/s in isogenic kidneys without rejection (P < 0.05). Magnetic resonance imaging parameters significantly correlated with the amount of cellular infiltration and renal fibrosis observed histologically. CONCLUSIONS: Functional MRI allows detection of acute renal allograft rejection after allogenic ktx in mice. Functional MRI parameters correlate with cell infiltrates and fibrosis. Thus, MRI may be used noninvasively and longitudinally to investigate mechanisms of renal allograft rejection and evaluate novel therapeutic strategies in experimental studies. PMID- 26371535 TI - Encapsulating Sn(x)Sb Nanoparticles in Multichannel Graphene-Carbon Fibers As Flexible Anodes to Store Lithium Ions with High Capacities. AB - SnxSb intermetallic composites as high theoretical capacities anodes for lithium ion batteries (LIBs) suffer from the quick capacity fading owing to their huge volume change. In this study, flexible mats made up of SnxSb-graphene-carbon porous multichannel nanofibers are fabricated by an electrospinning method and succedent annealing treatment at 700 degrees C. The flexible mats as binder-free anodes show a specific capacity of 729 mA h/g in the 500th cycle at a current density of 0.1 A/g, which is much higher than those of graphene-carbon nanofibers, pure carbon nanofibers, and SnxSb-graphene-carbon nanofibers at the same cycle. The flexible mats could provide a reversible capacity of 381 mA h/g at 2 A/g, also higher than those of nanofibers, graphene-carbon nanofibers, and SnxSb-carbon nanofibers. It is found that the suitable nanochannels could accommodate the volume expansion to achieve a high specific capacity. Besides, the graphene serves as both conductive and mechanical-property additives to enhance the rate capacity and flexibility of the mats. The electrospinning technique combined with graphene modification may be an effective method to produce flexible electrodes for fuel cells, lithium ion batteries, and super capacitors. PMID- 26371537 TI - Synthesis of organic (trimethylsilyl)chalcogenolate salts Cat[TMS-E] (E = S, Se, Te): the methylcarbonate anion as a desilylating agent. AB - A high-yield synthesis of the class of (trimethylsilyl)chalcogenolate organic salts [Cat][TMS-E] (E = S, Se, Te; Cat = BMPyr, DMPyr, NMe4, nBu3MeP) is presented. The title compounds have been prepared by the strictly aprotic reaction between the respective bis(trimethylsilyl)chalcogenide (TMS2E) and methylcarbonate ionic liquids (ILs). This constitutes a novel reaction behavior of methylcarbonate ILs, acting as a nucleophilic desilylating agent and a Lewis base instead of as a Bronsted base. Thus prepared silylchalcogenolate salts represent an activated form of the multifunctional TMS2E reactant series. Pyrrolidinium TMS-S salts have proven to be excellent precursors for the synthesis of pyrrolidinium hexasulfides. The scope of the desilylation reaction can be extended to other silyl-bearing synthons such as (trimethylsilyl)azide and (trimethylsilyl)cyanide. PMID- 26371536 TI - Macrolides for chronic asthma. AB - BACKGROUND: Asthma is a chronic disease in which inflammation of the airways causes symptomatic coughing, wheezing, and difficult breathing. The inflammation may have different underlying causes, including a reaction to infection in the lungs. Macrolides are antibiotics with antimicrobial and antiinflammatory activities that have been used long-term to control asthma symptoms. OBJECTIVES: To assess the effects of macrolides for managing chronic asthma. SEARCH METHODS: We searched the Cochrane Airways Group Specialised Register up to April 2015. We also manually searched bibliographies of previously published reviews and conference proceedings and contacted study authors. We included records published in any language in the search. SELECTION CRITERIA: Randomised controlled clinical trials involving both children and adults with chronic asthma treated with macrolides versus placebo for more than four weeks . DATA COLLECTION AND ANALYSIS: Two reviewers independently examined all records identified in the searches then reviewed the full text of all potentially relevant articles before extracting data in duplicate from all included studies. MAIN RESULTS: Twenty three studies met the inclusion criteria, randomising a total of 1513 participants to receive macrolide or placebo. The quality of evidence was generally very low due to incomplete reporting of study methodology and clinical data, suspected publication bias, indirectness of study populations, risk of bias and imprecision (because of small numbers of patients and events). Most of the included studies reported data from patients with persistent or severe asthma, but inclusion criteria, interventions and outcomes were highly variable.Macrolides were not found to be better than placebo for the majority of clinical outcomes including exacerbations requiring hospital admission (odds ratio (OR) 0.98, 95% confidence interval (CI) 0.13 to 7.23; participants = 143; studies = 2; I(2) = 0%) or at least treatment with oral steroids (OR 0.82, 95% CI 0.43 to 1.57; participants = 290; studies = 5; I(2) = 0%). The evidence on symptom scales (standard mean difference (SMD) -0.04, 95% CI -0.36 to 0.28), asthma control (SMD -0.05, 95% CI -0.26 to 0.15), quality of life (mean difference (MD) 0.06, 95% CI -0.12 to 0.24) and rescue medication use (MD -0.26, 95% CI -0.65 to 0.12) was all of very low quality and did not show a benefit of macrolide treatment. There was some evidence that macrolides led to some improvement in lung function (forced expiratory volume in one second (FEV1): MD 0.08, 95% CI 0.02 to 0.14), although not on all the measures we assessed. Measures of bronchial hyperresponsiveness were too varied to pool, but most studies showed no clear benefit of macrolide over placebo. Two studies recruiting people taking regular oral corticosteroids suggested macrolides may have a steroid-sparing effect in this population. Macrolides were well tolerated with respect to severe adverse events, although less than half of the studies reported the outcome (OR 0.80, 95% CI 0.24 to 2.68; participants = 434; studies = 7; I(2) = 0%). Reporting of specific side effects was too patchy across studies to analyse meaningfully. As already reported in the previous versions of the systematic review, biomarkers of asthma activity, such as sputum and serum level of eosinophil cationic protein (ECP) or sputum and serum eosinophils, were lower in patients treated with macrolides, but this was not associated with clinical benefits.Two within-study subgroup analyses showed a possible benefit of macrolides for non-eosinophilic asthma, but it was not possible to investigate this further using the data available for this review. AUTHORS' CONCLUSIONS: Existing evidence does not show macrolides to be better than placebo for the majority of clinical outcomes. However, they may have a benefit on some measures of lung function, and we cannot rule out the possibility of other benefits or harms because the evidence is of very low quality due to heterogeneity among patients and interventions, imprecision and reporting biases.The review highlights the need for researchers to report clinically relevant outcomes accurately and completely using guideline definitions of exacerbations and validated scales. The possible benefit of macrolides in patients with non eosinophilic asthma based on subgroup analyses in two of the included studies may require further investigation. PMID- 26371538 TI - C-H functionalization at sterically congested positions by the platinum-catalyzed borylation of arenes. AB - Despite significant progress in the area of C-H bond functionalization of arenes, no general method has been reported for the functionalization of C-H bonds at the sterically encumbered positions of simple arenes, such as mesitylene. Herein, we report the development of the first platinum-based catalyst for C-H borylation of arenes and heteroarenes. Notably, this method exhibited high tolerance toward steric hindrance and provided rapid access to a series of 2,6-disubstituted phenylboronic esters, valuable building blocks for further elaborations. PMID- 26371540 TI - Correlative Cryogenic Spectromicroscopy to Investigate Selenium Bioreduction Products. AB - Accurate mapping of the composition and structure of minerals and associated biological materials is critical in geomicrobiology and environmental research. Here, we have developed an apparatus that allows the correlation of cryogenic transmission electron microscopy (cryo-TEM) and synchrotron hard X-ray microprobe (SHXM) data sets to precisely determine the distribution, valence state, and structure of selenium in biofilms sampled from a contaminated aquifer near Rifle, CO. Results were replicated in the laboratory via anaerobic selenate-reducing enrichment cultures. 16S rRNA analyses of field-derived biofilm indicated the dominance of Betaproteobacteria from the Comamonadaceae family and uncultivated members of the Simplicispira genus. The major product in field and culture derived biofilms is ~25-300 nm red amorphous Se0 aggregates of colloidal nanoparticles. Correlative analyses of the cultures provided direct evidence for the microbial dissimilatory reduction of Se(VI) to Se(IV) to Se0. Extended X-ray absorption fine-structure spectroscopy showed red amorphous Se0 with a first shell Se-Se interatomic distance of 2.339 +/- 0.003 A. Complementary scanning transmission X-ray microscopy revealed that these aggregates are strongly associated with a protein-rich biofilm matrix. These findings have important implications for predicting the stability and mobility of Se bioremediation products and understanding of Se biogeochemical cycling. The approach, involving the correlation of cryo-SHXM and cryo-TEM data sets from the same specimen area, is broadly applicable to biological and environmental samples. PMID- 26371542 TI - Defect related emission versus intersystem crossing: blue emitting ZnO/graphene oxide quantum dots. AB - In ref. [Nat. Nanotechnol., 2012, 7, 465-471] interesting optoelectronic properties of ZnO/graphene oxide (GO) composite were presented. Essentially, in the luminescence spectrum indirect optical transitions were identified to be from the epoxy group of GO (GOepoxy) to the valance band (Ev) of ZnO. Viz. 406 nm, L1: (LUMO+2)GOepoxy->Ev and 436 nm, L2: (LUMO)GOepoxy->Ev. Furthermore, the emission peak at ~550 nm was attributed to zinc interstitials (Znis) or oxygen vacancies (VOs) and shown to span from 350-650 nm (equivalent to a width of ~0.8 eV). In this report we accentuate two vital though largely ignored concerns as itemized in the following. (i) By considering the growth mechanism of ZnO in the composite, there is a certain possibility that these two bands (L1 and L2) may originate from intrinsic defects of ZnO such as Znis and extended Znis (ex-Znis). Or L1 and L2 might be intrinsic to GO. (ii) The 550 nm emission involves VOs and consists of two components with a typical width of ~0.3 eV. Here we present the results of a thorough investigation confirming the presence of Znis, ex-Znis and intrinsic emission from GO. We also note that during the synthesis the presence of dimethyl formamide significantly affected the emission from GO in addition to some chemical modifications. Apart from these, we have discussed other crucial factors which require deeper attention in the context of luminescence from complex systems such as those present. PMID- 26371543 TI - Beamforming effects on generalized Nakagami imaging. AB - Ultrasound tissue characterization is crucial for the detection of tissue abnormalities. Since the statistics of the backscattered ultrasound signals strongly depend on density and spatial arrangement of local scatterers, appropriate modeling of the backscattered signals may be capable of providing unique physiological information on local tissue properties. Among various techniques, the Nakagami imaging, realized in a window-based estimation scheme, has a good performance in assessing different scatterer statistics in tissues. However, inconsistent m values have been reported in literature and obtained only from a local tissue region, abating the reliability of Nakagami imaging in tissue characterization. The discrepancies in m values in relevant literature may stem from the nonuniformity of the ultrasound image resolution, which is often neglected. We therefore hypothesized that window-based Nakagami m estimation was highly associated with the regional spatial resolution of ultrasound imaging. To test this hypothesis, our study investigated the effect of beamforming methods, including synthetic aperture (SA), coherent plane wave compounding (CPWC), multi focusing (MF), and single-focusing (SF), on window-based m parameter estimation from the perspective of the resolution cell. The statistics of m parameter distribution as a function of imaging depth were characterized by their mean, variance, and skewness. The phantom with a low scatterer density (16 scatterers mm(-3)) had significantly lower m values compared to the ones with high scatterer densities (32 and 64 scatterers mm(-3)). Results from the homogeneous phantom with 64 scatterers mm(-3) showed that SA, MF, and CPWC had relatively uniform lateral resolutions compared to SF and thus relatively constant m estimates at different imaging depths. Our findings suggest that an ultrasound imaging regime exhibiting invariant spatial resolution throughout the entire imaging field of view would be the most appropriate for Nakagami imaging for tissue characterization. PMID- 26371544 TI - Improved photoelectrochemical water oxidation by the WO3/CuWO4 composite with a manganese phosphate electrocatalyst. AB - We describe a composite of the n-type semiconductors for the photoelectrochemical oxygen evolution reaction (OER). A simple drop-casting technique of mixed precursors and a one-step annealing process were used in the synthesis of the WO3/CuWO4 composite. The composite showed improved photocurrent for water oxidation compared to either of the two compounds individually. We discuss possible electron-hole separation mechanisms in two semiconductors comprising a primary photon-absorbing semiconductor of CuWO4 with a secondary semiconductor of WO3. When the WO3/CuWO4 composite is simultaneously irradiated, the photogenerated hole from the WO3 valence band transfers to CuWO4, which results in an enhanced charge separation of CuWO4. Furthermore, the OER catalytic activity of manganese phosphate (MnPO) was compared to manganese oxide nanoparticles (Mn2O3) by electrochemical measurements, showing that the manganese phosphate was more efficient for the OER reaction. To investigate the effect of catalysts on semiconductors, manganese phosphate was deposited on the WO3/CuWO4 composite. The result demonstrates the promise of manganese phosphate for improving the photocurrent as well as the stability of the WO3/CuWO4 composite. PMID- 26371545 TI - Angiogenic Profiling of Synthesized Carbon Quantum Dots. AB - A simple method was employed for the synthesis of green luminescent carbon quantum dots (CQDs) from styrene soot. The CQDs were characterized by transmission electron microscopy, X-ray photoelectron spectroscopy, Fourier transform infrared, and Raman spectroscopy. The prepared carbon quantum dots did not show cellular toxicity and could successfully be used for labeling cells. We also evaluated the effects of carbon quantum dots on the process of angiogenesis. Results of a chorioallantoic membrane (CAM) assay revealed the significant decrease in the density of branched vessels after their treatment with CQDs. Further application of CQDs significantly downregulated the expression levels of pro-angiogenic growth factors like VEGF and FGF. Expression of VEGFR2 and levels of hemoglobin were also significantly lower in CAMs treated with CQDs, indicating that the CQDs inhibit angiogenesis. Data presented here also show that CQDs can selectively target cancer cells and therefore hold potential in the field of cancer therapy. PMID- 26371546 TI - Signatures of bond formation and bond scission dynamics in dissociative electron attachment to methane. AB - We present a combined experimental and theoretical investigation of the dynamics and angular dependence of dissociative electron attachment to methane. We show that a triply degenerate (T2) Feshbach resonance is responsible for the broad 10 eV dissociation peak in methane. This resonance alone is shown to correlate asymptotically to the various dissociation channels observed experimentally. The molecular-frame entrance amplitude for electron attachment is calculated for each component of the threefold degenerate resonance. By investigating the topology of the anion potential energy surfaces, we deduce the main pathways to two- and three-body breakup channels involving both bond scission and bond formation. The computed fragment angular distributions reproduce the main trends of the experimental measurements. PMID- 26371548 TI - The energetic viability of an unexpected skeletal rearrangement in cyclooctatin biosynthesis. AB - Results of density functional theory calculations on possible mechanisms for formation of the diterpenoid cyclooctatin are described. These results are consistent with the involvement of an unexpected 1,3-alkyl shift that interconverts two cyclopropylcarbinyl carbocations and interchanges the positions of two carbon atoms in an 8-membered ring. Predictions for future experiments to provide further support of this mechanism also are described. PMID- 26371549 TI - Benchmarking Electronic Excitation Energies and Transitions in Peptide Radicals. AB - Excited electronic states in several radical chromophores representing photochemically active groups in peptide and protein radicals and cation radicals were investigated computationally using equation-of-motion coupled cluster (EOM CCSD) and time-dependent density functional theory (TD-DFT) methods. The calculations identified the main transitions responsible for photodissociations of gas-phase peptide cation radicals in the near-UV region of the spectrum. Analysis of the EOM-CCSD benchmarks showed that no TD-DFT method was universally accurate across the various radical motifs that included Calpha-amide, aminoketyl, formamidyl, guanidyl, carbamyl, benzyl, phenoxy, and tautomeric dihydrophenyl and imidazolyl radicals. Overall, the omegaB97XD, M06-2X, and LC BLYP hybrid functionals showed acceptable performance when benchmarked against EOM-CCSD calculations. However, the performance of these TD-DFT methods depended on the nature of the radical chromophore, emphasizing the need for benchmarking and careful analysis. PMID- 26371550 TI - Spirobifluorene-2,7-dicarbazole-4'-phosphine Oxide as Host for High-Performance Single-Layer Green Phosphorescent OLED Devices. AB - A new host material based on the 2,7,4'-substituted spirobifluorene platform has been designed and used in single-layer phosphorescent OLED with very high efficiency (EQE = 13.2%) and low turn-on voltage (2.4 V). This performance is among the best reported for green single-layer PhOLEDs and may open new avenues in the design of host materials for single-layer devices. PMID- 26371551 TI - The molecular mechanism of nuclear transport revealed by atomic-scale measurements. AB - Nuclear pore complexes (NPCs) form a selective filter that allows the rapid passage of transport factors (TFs) and their cargoes across the nuclear envelope, while blocking the passage of other macromolecules. Intrinsically disordered proteins (IDPs) containing phenylalanyl-glycyl (FG)-rich repeats line the pore and interact with TFs. However, the reason that transport can be both fast and specific remains undetermined, through lack of atomic-scale information on the behavior of FGs and their interaction with TFs. We used nuclear magnetic resonance spectroscopy to address these issues. We show that FG repeats are highly dynamic IDPs, stabilized by the cellular environment. Fast transport of TFs is supported because the rapid motion of FG motifs allows them to exchange on and off TFs extremely quickly through transient interactions. Because TFs uniquely carry multiple pockets for FG repeats, only they can form the many frequent interactions needed for specific passage between FG repeats to cross the NPC. PMID- 26371552 TI - NOCA-1 functions with gamma-tubulin and in parallel to Patronin to assemble non centrosomal microtubule arrays in C. elegans. AB - Non-centrosomal microtubule arrays assemble in differentiated tissues to perform mechanical and transport-based functions. In this study, we identify Caenorhabditis elegans NOCA-1 as a protein with homology to vertebrate ninein. NOCA-1 contributes to the assembly of non-centrosomal microtubule arrays in multiple tissues. In the larval epidermis, NOCA-1 functions redundantly with the minus end protection factor Patronin/PTRN-1 to assemble a circumferential microtubule array essential for worm growth and morphogenesis. Controlled degradation of a gamma-tubulin complex subunit in this tissue revealed that gamma tubulin acts with NOCA-1 in parallel to Patronin/PTRN-1. In the germline, NOCA-1 and gamma-tubulin co-localize at the cell surface, and inhibiting either leads to a microtubule assembly defect. gamma-tubulin targets independently of NOCA-1, but NOCA-1 targeting requires gamma-tubulin when a non-essential putatively palmitoylated cysteine is mutated. These results show that NOCA-1 acts with gamma tubulin to assemble non-centrosomal arrays in multiple tissues and highlight functional overlap between the ninein and Patronin protein families. PMID- 26371553 TI - The primary sigma factor in Escherichia coli can access the transcription elongation complex from solution in vivo. AB - The sigma subunit of bacterial RNA polymerase (RNAP) confers on the enzyme the ability to initiate promoter-specific transcription. Although sigma factors are generally classified as initiation factors, sigma can also remain associated with, and modulate the behavior of, RNAP during elongation. Here we establish that the primary sigma factor in Escherichia coli, sigma(70), can function as an elongation factor in vivo by loading directly onto the transcription elongation complex (TEC) in trans. We demonstrate that sigma(70) can bind in trans to TECs that emanate from either a sigma(70)-dependent promoter or a promoter that is controlled by an alternative sigma factor. We further demonstrate that binding of sigma(70) to the TEC in trans can have a particularly large impact on the dynamics of transcription elongation during stationary phase. Our findings establish a mechanism whereby the primary sigma factor can exert direct effects on the composition of the entire transcriptome, not just that portion that is produced under the control of sigma(70)-dependent promoters. PMID- 26371555 TI - Codon-level information improves predictions of inter-residue contacts in proteins by correlated mutation analysis. AB - Methods for analysing correlated mutations in proteins are becoming an increasingly powerful tool for predicting contacts within and between proteins. Nevertheless, limitations remain due to the requirement for large multiple sequence alignments (MSA) and the fact that, in general, only the relatively small number of top-ranking predictions are reliable. To date, methods for analysing correlated mutations have relied exclusively on amino acid MSAs as inputs. Here, we describe a new approach for analysing correlated mutations that is based on combined analysis of amino acid and codon MSAs. We show that a direct contact is more likely to be present when the correlation between the positions is strong at the amino acid level but weak at the codon level. The performance of different methods for analysing correlated mutations in predicting contacts is shown to be enhanced significantly when amino acid and codon data are combined. PMID- 26371554 TI - Abundant toxin-related genes in the genomes of beneficial symbionts from deep-sea hydrothermal vent mussels. AB - Bathymodiolus mussels live in symbiosis with intracellular sulfur-oxidizing (SOX) bacteria that provide them with nutrition. We sequenced the SOX symbiont genomes from two Bathymodiolus species. Comparison of these symbiont genomes with those of their closest relatives revealed that the symbionts have undergone genome rearrangements, and up to 35% of their genes may have been acquired by horizontal gene transfer. Many of the genes specific to the symbionts were homologs of virulence genes. We discovered an abundant and diverse array of genes similar to insecticidal toxins of nematode and aphid symbionts, and toxins of pathogens such as Yersinia and Vibrio. Transcriptomics and proteomics revealed that the SOX symbionts express the toxin-related genes (TRGs) in their hosts. We hypothesize that the symbionts use these TRGs in beneficial interactions with their host, including protection against parasites. This would explain why a mutualistic symbiont would contain such a remarkable 'arsenal' of TRGs. PMID- 26371556 TI - The effects of a deleterious mutation load on patterns of influenza A/H3N2's antigenic evolution in humans. AB - Recent phylogenetic analyses indicate that RNA virus populations carry a significant deleterious mutation load. This mutation load has the potential to shape patterns of adaptive evolution via genetic linkage to beneficial mutations. Here, we examine the effect of deleterious mutations on patterns of influenza A subtype H3N2's antigenic evolution in humans. By first analyzing simple models of influenza that incorporate a mutation load, we show that deleterious mutations, as expected, act to slow the virus's rate of antigenic evolution, while making it more punctuated in nature. These models further predict three distinct molecular pathways by which antigenic cluster transitions occur, and we find phylogenetic patterns consistent with each of these pathways in influenza virus sequences. Simulations of a more complex phylodynamic model further indicate that antigenic mutations act in concert with deleterious mutations to reproduce influenza's spindly hemagglutinin phylogeny, co-circulation of antigenic variants, and high annual attack rates. PMID- 26371558 TI - High-Throughput Synthesis and Screening of Titania-Based Photocatalysts. AB - Titanium dioxide is widely known as a prominent photocatalyst material and research in this area has increased substantially over the last decades. However, the photoactivity of TiO2 is hindered by several factors, such as a relatively high photogenerated electron-hole recombination rate and a wide bandgap of ~ 3.2 eV, rendering it inactive under visible light. Approaches to optimize the TiO2 photocatalyst, either by altering its morphological or chemical properties, have been conducted for many years, yet further modification of this semiconductor has the potential to yield photocatalysts with excellent properties and higher photocatalytic activity. This could be effectively explored using combinatorial synthesis coupled with high-throughput characterization approaches. Such an approach has been widely applied for the discovery of new functional materials, including photocatalysts. By using high-throughput synthesis and characterization technology, preparation and screening of materials on small sample scales can be accelerated; hence, new TiO2-based photocatalysts with enhanced photocatalytic activity can be acquired more rapidly. Additionally, the large database of materials being systematically examined will greatly build our fundamental understanding of the relation between materials structure/composition and photocatalytic activity. This review details various high-throughput syntheses and characterization techniques applied to improve the photocatalytic properties of TiO2 materials and discuss several challenges that have been raised or may be encountered in the future when using this approach. PMID- 26371557 TI - Establishing the role of ATP for the function of the RIG-I innate immune sensor. AB - Retinoic acid-inducible gene I (RIG-I) initiates a rapid innate immune response upon detection and binding to viral ribonucleic acid (RNA). This signal activation occurs only when pathogenic RNA is identified, despite the ability of RIG-I to bind endogenous RNA while surveying the cytoplasm. Here we show that ATP binding and hydrolysis by RIG-I play a key role in the identification of viral targets and the activation of signaling. Using biochemical and cell-based assays together with mutagenesis, we show that ATP binding, and not hydrolysis, is required for RIG-I signaling on viral RNA. However, we show that ATP hydrolysis does provide an important function by recycling RIG-I and promoting its dissociation from non-pathogenic RNA. This activity provides a valuable proof reading mechanism that enhances specificity and prevents an antiviral response upon encounter with host RNA molecules. PMID- 26371559 TI - Association of the recurrence of vocal leukoplakia with MDM2-309 variants over a 2-year period: a prospective study. AB - CONCLUSION: MDM2-309 polymorphism variant genotypes decrease the risk of recurrence in vocal leukoplakia. OBJECTIVE: The results of a previous study 2 years ago showed the effect of mouse double minute 2 homolog (MDM2) SNP309 polymorphisms in people with laryngeal carcinoma and vocal leukoplakia (a pre cancerous laryngeal carcinoma lesion). This prospective, clinical trial was performed to assess the relationship between MDM2-309 polymorphism variants and recurrence/cancerization rates in people with vocal leukoplakia over a 2-year period. PARTICIPANTS AND METHOD: A total of 61 post-operative patients with vocal leukoplakia participated in this prospective, observational, 2-year, follow-up study, and were genotyped for the MDM2-309 gene using pyrosequencing. Recurrence and cancerization rates were used to assess the relationship between the clinical outcome and the genotype variants. RESULTS: The recurrence rate in the GT genotypes group was lower than that in the normal TT genotype group (17.2% vs 50%, p = 0.05) and there was a significantly lower recurrence rate in the GG genotype group than in the normal TT genotype group (10% vs 50%, p = 0.03). However, there was no statistically significant difference in the cancerization rate between the MDM2-309 variant (GT + GG) genotypes group and the normal TT genotype group (12.2% vs 8.3%, p > 0.05) over the 2-year follow-up period. PMID- 26371560 TI - Hierarchical Structure of Supramolecular Polymers Formed by N,N'-Di(2 ethylhexyl)urea in Solutions. AB - Supramolecular chain polymers formed by N,N'-di(2-ethylhexyl)urea (EHU) dissolved at low concentrations (up to 0.1 mole fraction) in heptane were investigated with the use of the dielectric spectroscopy. The experimental data show an exceptional ability of the chains for the antiparallel self-aggregation due to dipole-dipole interactions, leading to an anomalous dependence of the static permittivity of EHU + heptane solutions on temperature and concentration of the urea. The primary molecular assembly into polymeric chains is therefore followed by a secondary bundling of the chains which facilitates a longitudinal translation of the chains. That peculiarity and an asymmetry of the alkyl substituent in the EHU molecule making the system a mixture of diastereoisomers of unfavorable packing of the side group, are the most probable molecular mechanisms which prevent the crystallization of EHU-the only known liquid urea derivative. PMID- 26371561 TI - How many injections did you miss last month? A simple question to predict interferon beta-1a adherence in multiple sclerosis. AB - OBJECTIVES: Adherence to treatment is of utmost importance in multiple sclerosis (MS) to achieve full benefits from disease-modifying treatments. Thus, we investigated predictors of adherence to interferon beta-1a. METHODS: 114 relapsing-remitting MS subjects were recruited and followed-up during 1.536 +/- 0.961 years. RebiSmart(r) (Ares Trading SA, Coinsins, Switzerland), an electronic auto-injector, allows real-time recording of adherence which was retrospectively evaluated, and subjects were categorized accordingly: fully adherent (if no doses were missed), early or late missing (if missing the first dose during the first month of observation or later). The occurrence of clinical relapses and the annualized relapse rate (ARR) were prospectively recorded. RESULTS: Adherence was 95.0 +/- 9.0%. Early missing (n = 17, 14.9%) was more likely to be associated with the occurrence of a clinical relapse (OR = 4.155; p = 0.018), but not late missing (n = 54, 47.4%) (OR = 1.454; p = 0.408), as compared to fully adherent (n = 43, 37.7%). Adherence was lower in early missing, as compared to late missing (p < 0.001). The ARR was higher in early missing, as compared to late missing and to fully adherent (p < 0.001). CONCLUSION: MS subjects missing an injection early presented lower adherence, and a fourfold chance of having a relapse, suggesting a simple way to assess and categorize adherence in a clinical, real-life setting, where lack of time often prevents more thorough evaluations. PMID- 26371562 TI - Correction. PMID- 26371563 TI - Physicians Should Counsel Adolescents on the Harms of Sexting. PMID- 26371565 TI - Should Preparticipation Cardiovascular Screening of Athletes Include ECG? Yes: Screening ECG Is Cost-Effective. PMID- 26371566 TI - Should Preparticipation Cardiovascular Screening of Athletes Include ECG? No: There Is Not Enough Evidence to Support Including ECG in the Preparticipation Sports Evaluation. PMID- 26371569 TI - Diagnosis and Management of Foodborne Illness. AB - The Centers for Disease Control and Prevention estimates that each year, one in six Americans will experience a foodborne illness. The most common causes in the United States are viruses, such as norovirus; bacteria, such as Salmonella, Escherichia coli, Campylobacter, and Listeria; and parasites, such as Toxoplasma gondii and Giardia. Resources are available to educate consumers on food recalls and proper handling, storage, and cooking of foods. Diagnosis and management of a foodborne illness are based on the history and physical examination. Common symptoms of foodborne illnesses include vomiting, diarrhea (with or without blood), fever, abdominal cramping, headache, dehydration, myalgia, and arthralgias. Definitive diagnosis can be made only through stool culture or more advanced laboratory testing. However, these results should not delay empiric treatment if a foodborne illness is suspected. Empiric treatment should focus on symptom management, rehydration if the patient is clinically dehydrated, and antibiotic therapy. Foodborne illnesses should be reported to local and state health agencies; reporting requirements vary among states. PMID- 26371570 TI - The Preparticipation Sports Evaluation. AB - The preparticipation physical evaluation is a commonly requested medical visit for amateur and professional athletes of all ages. The overarching goal is to maximize the health of athletes and their safe participation in sports. Although studies have not found that the preparticipation physical evaluation prevents morbidity and mortality associated with sports, it may detect conditions that predispose the athlete to injury or illness and can provide strategies to prevent injuries. Clearance depends on the outcome of the evaluation and the type of sport (and sometimes position or event) in which the athlete participates. All persons undergoing a preparticipation physical evaluation should be questioned about exertional symptoms, presence of a heart murmur, symptoms of Marfan syndrome, and family history of premature serious cardiac conditions or sudden death. The physical examination should focus on the cardiovascular and musculoskeletal systems. U.S. medical and athletic organizations discourage screening electrocardiography and blood and urine testing in asymptomatic patients. Further evaluation should be considered for persons with heart or lung disease, bleeding disorders, musculoskeletal problems, history of concussion, or other neurologic disorders. PMID- 26371571 TI - Top 20 Research Studies of 2014 for Primary Care Physicians. AB - A team of primary care clinicians with expertise in evidence-based medicine performed monthly surveillance of more than 110 English-language clinical research journals during 2014, and identified 255 studies that had the potential to change how family physicians practice. Each study was critically appraised and summarized, focusing on its relevance to primary care practice, validity, and likelihood that it could change practice. A validated tool was used to obtain feedback from members of the Canadian Medical Association about the clinical relevance of each POEM (patient-oriented evidence that matters) and the benefits they expect for their practice. This article, the fourth installment in this annual series, summarizes the 20 POEMs based on original research studies judged to have the greatest impact on practice for family physicians. Key studies for this year include advice on symptomatic management and prognosis for acute respiratory infections; a novel and effective strengthening treatment for plantar fasciitis; a study showing that varenicline plus nicotine replacement is more effective than varenicline alone; a network meta-analysis concluding that angiotensin-converting enzyme inhibitors are preferred over angiotensin II receptor blockers; the clear benefits of initial therapy with metformin over other agents in patients with diabetes mellitus; and important guidance on the use of anticoagulants. PMID- 26371572 TI - Development of a Rash After Hot Tub Use. PMID- 26371573 TI - Insulin Sensitizers for Treatment of Menstrual Irregularities Associated with PCOS. PMID- 26371574 TI - Late Presentation to Prenatal Care. PMID- 26371577 TI - Bronchodilators for Bronchiolitis. PMID- 26371578 TI - Food Poisoning. PMID- 26371580 TI - Respiratory inhibition after crying or gastroesophageal reflux and feeding hypoxemia in infants. AB - OBJECTIVE: The objective of this study is to present information on respiratory inhibition after crying (RIAC), feeding hypoxemia, and respiratory inhibition after gastroesophageal reflux (RIGER) to medical staff caring for infants. METHODS: The author reviewed investigations of these conditions. RESULTS: These conditions have been observed in full-term healthy infants, and they are accompanied clinically by central cyanosis and a decrease in SpO2 to less than 70%. These conditions are easily diagnosed using pulse oximetry. Among Japanese infants with a gestational age of 36 weeks or older, the incidence of RIAC and feeding hypoxemia is 24% and 32%, respectively. The incidence of RIGER is approximately 4%. Feeding hypoxemia occurs significantly more often during bottle feeding than during breastfeeding. RIAC, feeding hypoxemia, and RIGER are significantly associated with each other. The risk factors are maternal smoking during pregnancy, threatened premature labor, twin gestation, asymmetric intrauterine growth restriction, and abnormal cranial ultrasound findings. Almost all infants recover from RIAC by day 7 after birth. Some infants with feeding hypoxemia require additional assistance and monitoring by nursing staff until the day of discharge. CONCLUSIONS: Medical staff caring for infants should note the presence of RIAC, feeding hypoxemia, and RIGER. PMID- 26371579 TI - Emotional variability and clarity in depression and social anxiety. AB - Recent research has underscored the importance of elucidating specific patterns of emotion that characterise mental disorders. We examined two emotion traits, emotional variability and emotional clarity, in relation to both categorical (diagnostic interview) and dimensional (self-report) measures of major depressive disorder (MDD) and social anxiety disorder (SAD) in women diagnosed with MDD only (n = 35), SAD only (n = 31), MDD and SAD (n = 26) or no psychiatric disorder (n = 38). Results of the categorical analyses suggest that elevated emotional variability and diminished emotional clarity are transdiagnostic of MDD and SAD. More specifically, emotional variability was elevated for MDD and SAD diagnoses compared to no diagnosis, showing an additive effect for co-occurring MDD and SAD. Similarly diminished levels of emotional clarity characterised all three clinical groups compared to the healthy control group. Dimensional findings suggest that although emotional variability is associated more consistently with depression than with social anxiety, emotional clarity is associated more consistently with social anxiety than with depression. Results are interpreted using a threshold and dose-response framework. PMID- 26371582 TI - Primary Cardiac Osteosarcoma: AIRP Best Cases in Radiologic-Pathologic Correlation. PMID- 26371583 TI - Adult Cardiac Valvular Disease for the General Radiologist: Resident and Fellow Education Feature. PMID- 26371584 TI - Wires, Catheters, and More: A Primer for Residents and Fellows Entering Interventional Radiology: Resident and Fellow Education Feature. PMID- 26371585 TI - Abernethy Malformation. PMID- 26371586 TI - Postsurgical Imaging of the Oral Cavity and Oropharynx: What Radiologists Need to Know-Erratum. PMID- 26371587 TI - Body MR Imaging: Artifacts, k-Space, and Solutions-Erratum. PMID- 26371588 TI - Proximal Femoral Fractures: What the Orthopedic Surgeon Wants to Know-Erratum. PMID- 26371590 TI - Mechanical properties of a mature biofilm from a wastewater system: from microscale to macroscale level. AB - A fundamental understanding of biofilm mechanical stability is critical in order to describe detachment and develop biofouling control strategies. It is thus important to characterise the elastic deformation and flow behaviour of the biofilm under different modes of applied force. In this study, the mechanical properties of a mature wastewater biofilm were investigated with methods including macroscale compression and microscale indentation using atomic force microscopy (AFM). The mature biofilm was found to be mechanically isotropic at the macroscale level as its mechanical properties did not depend on the scales and modes of loading. However, the biofilm showed a tendency for mechanical inhomogeneity at the microscale level as indentation progressed deeper into the matrix. Moreover, it was observed that the adhesion force had a significant influence on the elastic properties of the biofilm at the surface, subjected to microscale tensile loading. These results are expected to inform a damage-based model for biofilm detachment. PMID- 26371589 TI - A toll-like receptor 9 (rs352140) variant is associated with placental inflammation in newborn infants. AB - OBJECTIVE: Chorioamnionitis contributes to premature birth and associated postnatal morbidity. The genetic basis of altered immune responses underlying placental inflammation (PI) remains understudied. The aim of this study was to evaluate the relationship among TLR signaling pathway polymorphisms and different patterns of PI. METHODS: Prospective cohort study in infants involving cord blood collection and placental examination for PI. One hundred and fifty-nine infants enrolled in study out of which 28 were term (eight with PI) and 131 preterm (47 with PI). DNA from blood was genotyped for SNPs in TLR2, 4, 5, 9, NFKBI, NFKBIA, TIRAP, and IRAK1 genes using multiplexed single base extension assay. RESULTS: While there were no differences in BW, GA, gender, race, and SPL among infants with or without PI, there was a higher incidence of PPROM, maternal smoking, drug use, and clinical chorioamnionitis among infants with PI. Out of nine TLR variants, only CT and/or TT genotypes of the TLR9 variant (rs352140) were significantly associated (p = 0.004) with any PI and maternal pattern of inflammation (p = 0.012) both by univariate analysis and logistic regression. CONCLUSIONS: The presence of a variant T allele in a common SNP (rs352140) in the TLR9 gene whose product recognizes bacterial DNA is associated with increased PI. PMID- 26371591 TI - Thermal mitigation of Pseudomonas aeruginosa biofilms. AB - Bacterial biofilms infect 2-4% of medical devices upon implantation, resulting in multiple surgeries and increased recovery time due to the very great increase in antibiotic resistance in the biofilm phenotype. This work investigates the feasibility of thermal mitigation of biofilms at physiologically accessible temperatures. Pseudomonas aeruginosa biofilms were cultured to high bacterial density (1.7 * 10(9) CFU cm(-2)) and subjected to thermal shocks ranging from 50 degrees C to 80 degrees C for durations of 1-30 min. The decrease in viable bacteria was closely correlated with an Arrhenius temperature dependence and Weibull-style time dependence, demonstrating up to six orders of magnitude reduction in bacterial load. The bacterial load for films with more conventional initial bacterial densities dropped below quantifiable levels, indicating thermal mitigation as a viable approach to biofilm control. PMID- 26371592 TI - An Italian matrix sentence test for the evaluation of speech intelligibility in noise. AB - OBJECTIVE: Development of an Italian matrix sentence test for the assessment of speech intelligibility in noise. DESIGN: The development of the test included the selection, recording, optimization with level adjustment, and evaluation of speech material. The training effect was assessed adaptively during the evaluation measurements with six lists of 20 sentences, using open- and closed set response formats. Reference data were established for normal-hearing listeners with adaptive measurements. Equivalence of the test lists was investigated using the open-set response format at three signal-to-noise ratios (SNRs). STUDY SAMPLE: A total of 55 normal-hearing Italian mother-tongue listeners. RESULTS: The evaluation measurements at fixed SNRs resulted in a mean speech reception threshold (SRT) of -7.3 +/- 0.2 dB SNR and slope of 13.3 +/- 1.2 %/dB. The major training effect of 1.5 dB was observed for the first two consecutive measurements. Mean SRTs of -6.7 +/- 0.7 dB SNR and -7.4 +/- 0.7 dB SNR were found from the third to the sixth adaptive measurement for open- and closed-set test response formats, respectively. CONCLUSIONS: A good agreement has been found between the SRTs and slope and those of other matrix tests. Since sentences are difficult to memorize, the Italian matrix test is suitable for repeated measurements. PMID- 26371593 TI - Self-Selected Walking Speed is Predictive of Daily Ambulatory Activity in Older Adults. AB - Daily ambulatory activity is associated with health and functional status in older adults; however, assessment requires multiple days of activity monitoring. The objective of this study was to determine the relative capabilities of self selected walking speed (SSWS), maximal walking speed (MWS), and walking speed reserve (WSR) to provide insight into daily ambulatory activity (steps per day) in community-dwelling older adults. Sixty-seven older adults completed testing and activity monitoring (age 80.39 [6.73] years). SSWS (R2 = .51), MWS (R2 = .35), and WSR calculated as a ratio (R2 = .06) were significant predictors of daily ambulatory activity in unadjusted linear regression. Cutpoints for participants achieving < 8,000 steps/day were identified for SSWS (<= 0.97 m/s, 44.2% sensitivity, 95.7% specificity, 10.28 +LR, 0.58 -LR) and MWS (<= 1.39 m/s, 60.5% sensitivity, 78.3% specificity, 2.79 +LR, 0.50 -LR). SSWS may be a feasible proxy for assessing and monitoring daily ambulatory activity in older adults. PMID- 26371594 TI - Impact of proprioception during the oral phase on initiating the swallowing reflex. AB - OBJECTIVES/HYPOTHESIS: We hypothesized that proprioceptive signals during the oral phase play a pivotal role in the initiation of pharyngeal phase during volitional swallowing. Therefore, we tested if swallowing could be modified by changing the amount of proprioceptive feedback from a number of different receptors while holding a food bolus in the mouth and clenching. STUDY DESIGN: Basic research. METHODS: Surface electromyography (sEMG) recordings of the masticatory muscles were obtained during volitional swallowing movements from seven healthy adults with no clinical history of swallowing difficulties. The swallowing procedure involved holding 5 ml of jelly on the tongue before swallowing it completely, according to visual cues on a computer display. Initiation of the swallowing reflex was detected by an anterior shift of the thyroid cartilage using a laser displacement sensor and by submental sEMG signals. To vary the proprioceptive input, the participants were instructed to occlude their teeth at various intensities (weak, intermediate, and strong) while holding the 5-ml jelly bolus on the tongue. RESULTS: Rectified and integrated sEMG (iEMG) signals obtained from the submental area showed two upward deflections. Contractile forces of the masseter muscles showed significant negative values for Pearson correlation coefficient against time intervals from the onset of the second submental iEMG deflection to the onset of the anterior shift of the thyroid cartilage in six of the seven participants (average -0.534, standard deviation 0.176). CONCLUSION: Contractile forces of the masseter muscles during occlusion tended to correlate negatively with electromechanical delays on suprahyoid muscle contraction. LEVEL OF EVIDENCE: NA Laryngoscope, 126:1595-1599, 2016. PMID- 26371595 TI - Impact of Cytomegalovirus Infection on Severe Hepatitis C Recurrence in Patients Undergoing Liver Transplantation. AB - BACKGROUND: The influence of cytomegalovirus (CMV) on recurrent hepatitis C virus (HCV) in liver grafts is controversial. Our aim was to investigate the association between CMV infection and disease and severe HCV recurrence (composite variable of presence of stage 3 to 4 fibrosis, need for retransplantation or death due to liver disease) in the first year after transplantation. METHODS: An observational, prospective, multicenter study was performed. The CMV replication was monitored by determining CMV viral load weekly during hospitalization after transplantation, twice monthly in the first 3 months after discharge, and at each follow-up visit until month 12. Liver fibrosis was assessed histologically by liver biopsy or transient elastometry. Pretransplant, intraoperative, and posttransplant variables were recorded. Multiple logistic regression was performed to study the impact of CMV on severe HCV recurrence. RESULTS: Ninety-eight patients were included. The CMV infection was detected in 48 patients (49%) in the first year posttransplant, of which 11 patients (22.9%) had CMV disease. Twenty-three patients (23.5%) had severe HCV recurrence. Of these, 17 (73.9%) developed stage 3 to 4 fibrosis, 4 (17.4%) died, and 2 (8.7%) underwent retransplantation. Only 7 of 12 (58.3%) seronegative recipients of a seropositive donor (positive donor/negative recipient [D+/R-]) received universal prophylaxis, and 10 of 12 (83.3%) D+/R- patients developed CMV replication. In the multivariate analysis, the presence of CMV D+/R- serodiscordance (odds ratio, 6.87; 95% confidence interval, 1.89-24.99; P = 0.003), and detection of a higher peak HCV viral load (odds ratio, 3.85; 95% confidence interval, 1.49-9.94; P = 0.005) were associated with severe HCV recurrence. CONCLUSIONS: Our results support an association between CMV D+/R- serodiscordance and severe HCV recurrence in patients undergoing liver transplantation for HCV liver disease. PMID- 26371596 TI - Platelet-derived Growth Factor-B Protects Rat Cardiac Allografts From Ischemia reperfusion Injury. AB - BACKGROUND: Microvascular dysfunction and cardiomyocyte injury are hallmarks of ischemia-reperfusion injury (IRI) after heart transplantation. Platelet-derived growth factors (PDGF) have an ambiguous role in this deleterious cascade. On one hand, PDGF may exert vascular stabilizing and antiapoptotic actions through endothelial-pericyte and endothelial-cardiomyocyte crosstalk in the heart; and on the other hand, PDGF signaling mediates neointimal formation and exacerbates chronic rejection in cardiac allografts. The balance between these potentially harmful and beneficial actions determines the final outcome of cardiac allografts. METHODS AND RESULTS: We transplanted cardiac allografts from Dark Agouti rat and Balb mouse donors to fully major histocompatibility complex mismatched Wistar Furth rat or C57 mouse recipients with a clinically relevant 2 hour cold ischemia and 1-hour warm ischemia. Ex vivo intracoronary delivery of adenovirus-mediated gene transfer of recombinant human PDGF-BB upregulated messenger RNA expression of anti-mesenchymal transition and survival factors BMP 7 and Bcl-2 and preserved capillary density in rat cardiac allografts at day 10. In mouse cardiac allografts PDGF receptor-beta, but not -alpha intragraft messenger RNA levels were reduced and capillary protein localization was lost during IRI. The PDGF receptor tyrosine kinase inhibitor imatinib mesylate and a monoclonal antibody against PDGF receptor-alpha enhanced myocardial damage evidenced by serum cardiac troponin T release in the rat and mouse cardiac allografts 6 hours after reperfusion, respectively. Moreover, imatinib mesylate enhanced rat cardiac allograft vasculopathy, cardiac fibrosis, and late allograft loss at day 56. CONCLUSIONS: Our results suggest that PDGF-B signaling may play a role in endothelial and cardiomyocyte recovery from IRI after heart transplantation. PMID- 26371597 TI - Recurrent Primary Focal Segmental Glomerulosclerosis Managed With Intensified Plasma Exchange and Concomitant Monitoring of Soluble Urokinase-Type Plasminogen Activator Receptor-Mediated Podocyte beta3-integrin Activation. AB - BACKGROUND: Primary focal segmental glomerulosclerosis (FSGS) often causes nephrotic proteinuria and frequently results in end-stage renal disease and recurrence after kidney transplantation. Recent studies describe soluble urokinase-type plasminogen activator receptor (suPAR) as a circulating factor implicated in FSGS. METHODS: This single-center study included 12 adult patients with histologically proven primary FSGS (n = 2) or recurrent FSGS after transplantation (n = 10). The effect of plasma exchange (PE) on clinical outcome, suPAR levels, and in vitro podocyte beta3-integrin activation was investigated over a median of 11 (6-18) sessions of PE. RESULTS: The course of treatment was monitored in a total of 70 sessions of PE, which partly eliminated suPAR, with a mean reduction of 37 +/- 12% of serum concentration per session. However, a substantial rebound was observed between sessions, with suPAR levels reaching 99 +/- 22% of the pretreatment levels after a median of 4 days. Podocyte beta3 integrin activation dropped significantly after PE but rebounded within 4 days concomitant with a rising suPAR level. In 11 of 12 patients, multimodal treatment (including extensive PE) reduced proteinuria significantly (from 5.3 [2.0-7.8] to 1.0 [0.4-1.6] g/d), indicating clinical efficacy of the therapy. One patient suffered allograft loss due to FSGS recurrence. A persisting response was independent of a lasting reduction in the level of total suPAR because there was no sustained significant change in suPAR levels before and after the course of intensified treatment (3814 +/- 908 to 3595 +/- 521 pg/mL; P = 0.496). CONCLUSIONS: We conclude that multimodal therapy including extensive PE was associated with stabilization of recurrent FSGS and a temporary lowering of plasma suPAR as well as podocyte beta3-integrin activation. Whether a sustained lowering of total suPAR results in further improved outcomes requires additional study. PMID- 26371598 TI - The Dutch Transplantation in Vasculitis (DUTRAVAS) Study: Outcome of Renal Transplantation in Antineutrophil Cytoplasmic Antibody-associated Glomerulonephritis. AB - BACKGROUND: Data on the outcome of renal transplantation in antineutrophil cytoplasmic antibody-associated glomerulonephritis (AAGN) patients are still limited. In particular, how disease recurrence in the renal allograft defines graft outcome is largely unknown. Therefore, we conducted a multicenter observational clinical and histopathological study to establish recurrence rate of AAGN in the allograft and the impact of recurrence on allograft survival. METHODS: Using the nationwide Dutch Pathology Registry (PALGA), we retrospectively collected clinical and histopathological data of consecutive AAGN patients who had developed end-stage renal failure and received a kidney allograft in 1 of 6 Dutch university hospitals between 1984 and 2011. Transplant biopsies were scored using the Banff '09 classification. Renal disease recurrence was scored using the histopathological classification of AAGN. RESULTS: The posttransplantation recurrence rate of AAGN was 2.8% per patient year, accumulating to recurrence in a total of 11 of 110 AAGN patients within the first 5 years after transplantation. Four of these 11 patients lost their graft, with 1 year and 5-year graft survival rates of 94.5% and 82.8%, respectively. By multivariate analysis, AAGN recurrence was independently associated with subsequent graft loss. CONCLUSIONS: In this study in 110 Dutch patients, the recurrence rate of AAGN within 5 years after kidney transplantation appeared slightly higher than in previous reports. Moreover, recurrence of AAGN contributed independently to kidney allograft loss, emphasizing the importance of clinical vigilance, because early treatment might be critical to rescuing the allograft. PMID- 26371599 TI - Focal Segmental Glomerulosclerosis Recurrence: Soluble Urokinase Receptor Left Out? PMID- 26371600 TI - Association of very low prostate-specific antigen levels with increased cancer specific death in men with high-grade prostate cancer. AB - BACKGROUND: The objective of this study was to determine whether a very low presenting prostate-specific antigen (PSA) level was associated with greater prostate cancer-specific mortality (PCSM) among men with a Gleason score (GS) of 8 to 10. METHODS: The Surveillance, Epidemiology, and End Results program was used to identify 328,904 men diagnosed with clinicalT1 (cT1)-4N0M0 prostate cancer between 2004 and 2010. A multivariate Fine-Gray competing risks regression analysis was used to determine PCSM as a function of the PSA level (<= 2.5, 2.6 4, 4.1-10, 10.1-20, 20.1-40, or > 40 ng/mL) and GS (8-10 vs <= 7). RESULTS: The median follow-up was 38 months. Among men with GS 8-10 disease, with a PSA level of 4.1 to 10 ng/mL as the referent, the adjusted hazard ratio for PCSM for men was 2.15 with a PSA level <= 2.5 ng/mL (95% confidence interval [CI], 1.65-2.79; P < .001), 1.60 with a PSA level of 2.6 to 4 ng/mL (95% CI, 1.22-2.10; P = .001), 1.60 with a PSA level of 10.1 to 20 ng/mL (95% CI, 1.41-1.82; P < .001), 2.08 with a PSA level of 20.1 to 40 ng/mL (95% CI, 1.81-2.38; P < .001), and 3.23 with a PSA level > 40 ng/mL (95% CI, 2.85-3.65; P < .001). This suggested a U-shaped distribution. There was a significant interaction between the PSA level and GS (P(interaction) < .001) such that only a PSA level <= 2.5 ng/mL significantly predicted poorer PCSM among patients with GS 8-10 disease. CONCLUSIONS: Among patients with high-grade disease, patients with PSA levels <= 2.5 ng/mL or PSA levels of 2.6 to 4 ng/mL appear to have a higher risk for cancer-specific death in comparison with patients with PSA levels of 10.1 to 20 ng/mL, and this supports the notion that low PSA levels in GS 8-10 disease may be a sign of aggressive and very poorly differentiated or anaplastic low PSA-producing tumors. Patients with low-PSA, GS 8-10 disease should be considered for clinical trials studying the use of chemotherapy and other novel agents for very high-risk prostate cancers. PMID- 26371601 TI - Discussion of "Deductive derivation and turing-computerization of semiparametric efficient estimation" by Frangakis et al. PMID- 26371602 TI - Epiglottis collapse in adult obstructive sleep apnea: A systematic review. AB - OBJECTIVES/HYPOTHESIS: To systematically review the international literature evaluating the role of the epiglottis in snoring and obstructive sleep apnea and to explore possible treatment options available. DATA SOURCES: PubMed, Scopus, Embase, Google Scholar, Book Citation Index-Science, CINAHL, Conference Proceedings Citation Index-Science, The Cochrane Collaboration Databases, and Web of Science. REVIEW METHOD: The searches were performed from the first year of each database through March 5, 2015. RESULTS: Fourteen studies about the prevalence of epiglottis collapse in obstructive sleep apnea (OSA) were found. Most involved drug-induced sleep endoscopy studies that indirectly reported their findings about epiglottis collapse. The data suggests that the prevalence of epiglottis collapse in OSA is higher than previously described. The epiglottis has been implicated in 12% of cases of snoring, and sound originating from it has a higher pitch than palatal snoring. Continuous positive pressure (CPAP) surgery and positional therapy in the treatment of epiglottis collapse were also considered. Lateral position of the head may reduce the frequency of epiglottis collapse. With regard to CPAP, available reports suggest that it may accentuate collapse of the epiglottis. Surgery may help reduce snoring in some patients with a lax epiglottis and improve OSA in patients undergoing multilevel surgery. CONCLUSION: Knowledge regarding the role of the epiglottis in adult OSA and snoring patients is limited. The prevalence of this phenomenon in OSA seems to be greater than previously reported, and more research is needed to understand its role in OSA and the best way to treat it. LEVEL OF EVIDENCE: NA. PMID- 26371603 TI - Caustic oesophagitis in children: prevalence, the corrosive agents involved, and management from primary care through to surgery. AB - PURPOSE OF REVIEW: Caustic substance ingestion (CSI) remains a major health issue, particularly in developing countries, where laws are not effectively enforced. This review offers a thorough analysis of the current epidemiology, clinical features, management, treatment, and long-term complications of CSI in children. RECENT FINDINGS: Strong alkalis sold in liquid and granular forms, particularly crystalline grease cleaners (concentrated sodium hydroxide), are the principal causes of severe oesophageal damage. Currently, early endoscopy to assess the gastro-oesophageal mucosa is not considered necessary for all CSI cases. Oesophageal stricture is a major complication developing after CSI, and should be diagnosed and treated earlier, 10-14 days after CSI via commencement of a dilation program. Fluoroscopically guided oesophageal balloon dilatation seems to be safe, with a low frequency of complications and a high success rate. However, it should commence earlier than is currently the case, and should be performed gently, using balloons of gradually increasing diameter. If dilation fails after a few months, oesophageal replacement surgery should be performed. SUMMARY: Unfortunately, neither dilatation treatment nor oesophageal bypass surgery can prevent the development of oesophageal carcinoma, the incidence of which is high after CSI. The continuing unacceptably high incidence of CSI accidents would be reduced if corrosive materials were sold in their original childproof containers, highlighting the need for preventive and adult education programmes. PMID- 26371604 TI - The role of biofilm in chronic laryngitis and in head and neck cancer. AB - PURPOSE OF REVIEW: The importance of bacterial biofilm in the human body, both when associated in chronic infections and as the default mode of microbial growth in the normal flora, has been understood during the last two decades. The word biofilm has recently entered into clinical vocabulary especially in dentistry, and oral hygienists have begun to talk of oral or dental biofilm instead of oral plaque. Biofilm presence has been demonstrated widely in otorhinolaryngology, related to chronic infections of middle ear, paranasal sinuses and lymphoid tissue of adenoids and tonsils and to implanted materials; however, less literature exists considering the implication of biofilm to laryngeal infections or head and neck cancer. The research until now has been mainly descriptive and the mechanisms that lead to biofilm formation are unclear and thus there are limited options for specific treatment of biofilm infection. The focus of this article is to review the recent literature considering the bacterial biofilm in larynx and in head and neck surgery. RECENT FINDINGS: Bacterial biofilm has now also been implicated in chronic laryngitis. Among head and neck cancer patients, biofilm is the main reason for the short life cycle of indwelling devices such as voice prostheses and tracheal tubes. Recently, bacterial biofilm has been related to dysplasia and malignancies both as an aetiological factor and as a source of complications. SUMMARY: It has been shown that microbial biofilm is implicated in the mechanisms leading to chronic recalcitrant infections, implant contamination and even to dysplasia. Biofilm has an important role in finding new preventive measures and treatment of these diseases. PMID- 26371605 TI - Infective oesophagitis: epidemiology, cause, diagnosis and treatment options. AB - PURPOSE OF REVIEW: This review summarizes recent literature pertaining to infectious oesophagitis. RECENT FINDINGS: Infectious oesophagitis is an uncommon condition of the oesophagus caused by viral, bacterial or fungal agents. A compromised immune system is the most important risk factor for the development of infectious oesophagitis and HIV or AIDS and solid organ transplant patients are particularly at risk. Common symptoms of infectious oesophagitis include odynophagia and dysphagia, but it can be difficult to distinguish infectious oesophagitis from other causes of oesophagitis based on patient symptoms alone. Definitive diagnosis requires esophagoscopy with biopsy for histologic and microbiologic evaluation. Endoscopic findings differ based on cause. Overall, Candida albicans is the most common cause of infectious oesophagitis. Treatment of infectious oesophagitis is based on host immune status, the severity of infection and risk of complications. When seemingly adequate treatment is unsuccessful, alternative diagnoses should be entertained and additional biopsies and/or diagnostics obtained. SUMMARY: Recent research in infectious oesophagitis involves identifying preventive strategies for at-risk populations. Prevention may include use of probiotics, prophylactic medications and/or treatment of underlying immune dysfunction and could be important for susceptible individuals. PMID- 26371606 TI - Pediatric tracheotomy decannulation: a protocol for success. AB - PURPOSE OF REVIEW: Pediatric tracheotomy is a common procedure. Given the risk of morbidity and mortality associated with long-term placement, it is imperative that decannulation is considered once the indication for tracheotomy placement is corrected or resolved. In this article, we discuss the critical steps necessary for the assessment of readiness for decannulation, and we review the recent literature that supports several methods of evaluation that may be incorporated into a protocol for decannulation. RECENT FINDINGS: Recent literature related to the topics of pediatric tracheotomy and decannulation is limited to case series and retrospective reviews, though relatively large patient populations are encompassed within individual studies. The data presented support the use of routine predecannulation endoscopic exam, as well as progressive daytime and overnight inpatient capping trials to ensure adequate airway patency, capped polysomnography for patients with underlying obstructive sleep apnea and/or dynamic airway disease, and 24-h inpatient observation after decannulation to determine tolerance and detect early failures requiring tracheotomy replacement. SUMMARY: Although the assessment of readiness for decannulation may be challenging, several evaluative steps are recommended to ensure safe and effective decannulation in pediatric patients. Apparent variation in decannulation outcomes by underlying cause may herald the development of indication-specific decannulation protocols in the future. PMID- 26371607 TI - Management of oropharyngeal neurogenic dysphagia in adults. AB - PURPOSE OF REVIEW: This article reviews recent literature in the management of neurogenic oropharyngeal dysphagia (OPD) including assessment processes and treatments, with a specific focus on OPD as a result of stroke and Parkinson's disease. RECENT FINDINGS: A large number of high-quality systematic reviews were published that provide an excellent summary of current evidence across assessment and treatment of swallowing disorders. There is building interest and knowledge in technology in both the understanding and treatment of OPD including functional MRI, manometry, and noninvasive brain stimulation. SUMMARY: Neurologic disorders demonstrate a high prevalence of OPD resulting in significant decrement to health and healthcare costs. Novel technologies were reported in assessment and tracking of dysphagia as well as emerging innovative therapeutic options. PMID- 26371608 TI - Cryptococcus uniguttulatus Meningitis. PMID- 26371610 TI - Does HIV Infection Alter Parkinson Disease? AB - OBJECTIVE: To describe the clinical features, treatment(s), and outcomes of 15 HIV-infected patients with idiopathic Parkinson disease (PD) and sustained virus suppression and immunologic reconstitution, from a reference cohort of 9847 persons living with HIV (PLH). METHODS: This retrospective, single-center matched case-control 1:2 study included PLH-PD patients evaluated over a 12-year period (2002-2013) with mean follow-up of 6.5 years. PD clinical features and dopamine replacement therapy (DRT) were compared, and biologically relevant HIV data were assessed. RESULTS: PD prevalence in PLH was similar to that of the general population. At onset, clinical presentations and therapeutic management were similar for both groups. Rapidly effective DRT was well tolerated without combined antiretroviral therapy interactions or virus escape. At the end of the follow-up, compared with HIV-negative PD, PLH had a significantly lower median Unified Parkinson's Disease Rating Scale motor score (4 vs 14; P < 0.001), median Hoehn and Yahr stage (1 vs 2; P = 0.0005), and median Handipark scale score (2 vs 3; P = 0.0036) under the same daily DRT. One PLH underwent highly successful deep brain stimulation of the subthalamic nucleus. CONCLUSIONS: HIV-associated PD is similar to idiopathic PD with some features suggesting an HIV-induced functional adaptation of dopaminergic neurons that might counterbalance the PD-induced neuronal loss. Concurrent HIV infection does not compromise the outcome of idiopathic PD. PMID- 26371612 TI - The Use of Digital Impressions to Fabricate Tooth-Supported Partial Removable Dental Prostheses: A Clinical Report. AB - Impression making is a critical step in the fabrication of a partial removable dental prosthesis (RDP). A technique is described for making final impressions to fabricate partial RDPs for Kennedy class III patients using a computer-aided design and computer-assisted manufacturing digital impression system. PMID- 26371611 TI - Time and Money: The True Costs of Health Care Utilization for Patients Receiving "Free" HIV/Tuberculosis Care and Treatment in Rural KwaZulu-Natal. AB - BACKGROUND: HIV and tuberculosis (TB) services are provided free of charge in many sub-Saharan African countries, but patients still incur costs. METHODS: Patient-exit interviews were conducted in primary health care clinics in rural South Africa with representative samples of 200 HIV-infected patients enrolled in a pre-antiretroviral treatment (pre-ART) program, 300 patients receiving antiretroviral treatment (ART), and 300 patients receiving TB treatment. For each group, we calculated health expenditures across different spending categories, time spent traveling to and using services, and how patients financed their spending. Associations between patient group and costs were assessed in multivariate regression models. RESULTS: Total monthly health expenditures [1 USD = 7.3 South African Rand (ZAR)] were ZAR 171 [95% confidence interval (CI): 134 to 207] for pre-ART, ZAR 164 (95% CI: 141 to 187) for ART, and ZAR 122 (95% CI: 105 to 140) for TB patients (P = 0.01). Total monthly time costs (in hours) were 3.4 (95% CI: 3.3 to 3.5) for pre-ART, 5.0 (95% CI: 4.7 to 5.3) for ART, and 3.2 (95% CI: 2.9 to 3.4) for TB patients (P < 0.01). Although overall patient costs were similar across groups, pre-ART patients spent on average ZAR 29.2 more on traditional healers and ZAR 25.9 more on chemists and private doctors than ART patients, whereas ART patients spent ZAR 34.0 more than pre-ART patients on transport to clinics (P < 0.05 for all results). Thirty-one percent of pre-ART, 39% of ART, and 41% of TB patients borrowed money or sold assets to finance health care. CONCLUSIONS: Patients receiving nominally free care for HIV/TB face large private costs, commonly leading to financial distress. Subsidized transport, fewer clinic visits, and drug pick-up points closer to home could reduce costs for ART patients, potentially improving retention and adherence. Large expenditure on alternative care among pre-ART patients suggests that transitioning patients to ART earlier, as under HIV treatment-as-prevention policies, may not substantially increase patients' financial burden. PMID- 26371613 TI - Viable contribution of Tibetan sacred mountains in southwestern China to forest conservation. AB - The Tibetan sacred mountains (TSMs) cover a large area and may represent a landscape-scale conservation opportunity. We compared the conservation value of forests in these mountains with the conservation value of government-established nature reserves and unmanaged open-access areas in Danba County, southwestern China. We used Landsat satellite images to map forest cover and to estimate forest loss in 1974-1989, 1989-1999, and 1999-2013. The TSMs (n = 41) and nature reserves (n = 4) accounted for 21.6% and 29.7% of the county's land area, respectively. Remaining land was open-access areas (i.e., areas without any restrictions on resource use) (56.2%) and farmlands (2.2%). Within the elevation range suitable for forests, forest cover did not differ significantly between nature reserves (58.8%) and open-access areas (58.4%), but was significantly higher in TSMs (65.5%) after controlling for environmental factors such as aspect, slope, and elevation. The TSMs of great cultural importance had higher forest cover, but patrols by monastery staff were not necessarily associated with increased forest cover. The annual deforestation rate in nonsacred areas almost tripled in 1989-1999 (111.4 ha/year) relative to 1974-1989 (40.4 ha/year), whereas the rate in TSMs decreased in the later period (19.7 ha/year vs. 17.2 ha/year). The reduced forest loss in TSMs in 1989-1999 was possibly due to the renaissance of TSM worship and strengthened management by the local Buddhist community since late 1980s. The annual deforestation rate in Danba decreased dramatically to 4.4 ha/year in 1999-2013, which coincided with the implementation of a national ban on logging in 1998. As the only form of protected area across the Tibetan region during much of its history, TSMs have positively contributed to conserving forest at a landscape scale. Conservation of TSM forests largely relied on the strength of local religious institutions. Integrating community based conservation of TSMs within the government conservation network would benefit the conservation of the Tibetan region. PMID- 26371614 TI - Oral health-related quality of life in 6- to 12-year-old schoolchildren in Spain. AB - BACKGROUND: There is a lack of large epidemiological studies researching the major factors of the oral well-being in schoolchildren. AIMS: To quantify the impact of the different clinical conditions related to caries and periodontal and dento-facial anomalies on the quality of life captured by the Child-OIDP. DESIGN: A standardized epidemiological study was conducted on 2041 Spanish schoolchildren, aged 6-12 years, to assess caries and periodontal and dento facial disease. Data on oral health-related quality of life were collected using the Child-OIDP. Bivariate and multivariate analyses were performed to evaluate the modulating factors in the perceived oral well-being. RESULTS: The prevalence of impact in this sample was 45.7%, mostly for eating (24.3%) but also for smiling (16.2%); however, 72.5% of the subjects had at least one type of normative needs, mainly for periodontal treatment (52.3%), followed by caries (32.3%) and orthodontic treatments (20.6%). The main predictors of the impact on quality of life were perceived dental treatment needs, caries, and periodontal diseases. Also, some demographic (age and gender) and behavioural factors (consumption of sweets) modulated the impact on several domains. Moreover, subjects who rated their general health as good or very good reported a significantly better oral well-being than their counterparts. CONCLUSIONS: Pain and aesthetic-related domains (i.e., problems when eating or smiling) are the major components of the oral health-related quality of life perceived by Spanish schoolchildren. Perceived treatment needs as well as dental and periodontal status were the strongest predictors of oral well-being. PMID- 26371615 TI - Temporal flickering of contrast agents for enhanced optical imaging. AB - The temporal flickering of contrast agents that labels a biological sample is a unique modality for cellular imaging with single molecule sensitivity. It improves the signal-to-noise ratio statistics associated with the noisy in vivo environment and has promising applications in single particle tracking and super resolution microscopy techniques. The flickering can be triggered either statistically through the mechanism of temporal fluctuations of the emitter or through external modulation. The enriching toolbox of contrast agents that are feasible for biomedical imaging for the flickering methods will be discussed, with emphasis on the emerging field of flickering gold nanoparticles and the lock in detection mechanism. WIREs Nanomed Nanobiotechnol 2016, 8:439-448. doi: 10.1002/wnan.1375 For further resources related to this article, please visit the WIREs website. PMID- 26371616 TI - A systematic review of patient-reported outcome measures for chronic suppurative otitis media. AB - OBJECTIVE: The purpose of this review was to systematically appraise the world literature to identify existing patient-reported outcome measures (PROMs) for the assessment of outcomes in patients with chronic suppurative otitis media, to verify the diversity of the individual questionnaire items, to report the methods employed to evaluate the questionnaires, and to identify areas for development in the future. DATA SOURCES: Embase (January 1980-November 2014), MEDLINE (January 1946-November 2014), Cumulative Index to Nursing and Allied Health Literature (January 1981-November 2014), and PsycINFO (January 1806-November 2014). REVIEW METHODS: A systematic literature search was independently undertaken by the two authors according to predefined inclusion and exclusion criteria. RESULTS: Nine original articles were identified, which overall outlined the evaluation of four different questionnaires. CONCLUSIONS: This systematic appraisal of the world literature has identified four PROM questionnaires for use in patients with chronic suppurative otitis media. All four questionnaires evaluate reliability and validity using different psychometric methods. The Chronic Ear Survey questionnaire has been most broadly evaluated and disseminated. All four questionnaires assess static health status. There are many advantages to developing a dynamic one-hit questionnaire to assess the health status of patients having undergone an intervention for chronic suppurative otitis media. LEVEL OF EVIDENCE: NA Laryngoscope, 126:1458-1463, 2016. PMID- 26371617 TI - A randomized controlled trial on the efficacy of mindfulness-based cognitive therapy and a group version of cognitive behavioral analysis system of psychotherapy for chronically depressed patients. AB - OBJECTIVE: Mindfulness-based cognitive therapy (MBCT) has recently been proposed as a treatment option for chronic depression. The cognitive behavioral analysis system of psychotherapy (CBASP) is the only approach specifically developed to date for the treatment of chronically depressed patients. The efficacy of MBCT plus treatment-as-usual (TAU), and CBASP (group version) plus TAU, was compared to TAU alone in a prospective, bicenter, randomized controlled trial. METHOD: One hundred and six patients with a current DSM-IV defined major depressive episode and persistent depressive symptoms for more than 2 years were randomized to TAU only (N = 35), or to TAU with additional 8-week group therapy of either 8 sessions of MBCT (n = 36) or CBASP (n = 35). The primary outcome measure was the Hamilton Depression Rating Scale (24-item HAM-D, Hamilton, 1967) at the end of treatment. Secondary outcome measures were the Beck Depression Inventory (BDI; Beck, Steer, & Brown, 1996) and measures of social functioning and quality of life. RESULTS: In the overall sample as well as at 1 treatment site, MBCT was no more effective than TAU in reducing depressive symptoms, although it was significantly superior to TAU at the other treatment site. CBASP was significantly more effective than TAU in reducing depressive symptoms in the overall sample and at both treatment sites. Both treatments had only small to medium effects on social functioning and quality of life. CONCLUSIONS: Further studies should inquire whether the superiority of CBASP in this trial might be explained by the more active, problem-solving, and interpersonal focus of CBASP. PMID- 26371619 TI - Operative Versus Nonoperative Treatment of Displaced Intra-Articular Calcaneal Fractures: A Meta-Analysis of Randomized Controlled Trials. AB - OBJECTIVES: To compare the clinical outcomes of operative and nonoperative treatment for displaced intra-articular calcaneal fractures (DIACFs). DATA SOURCES: PubMed, Embase, Cochrane library, and ClinicalTrial.gov. STUDY SELECTION: Randomized controlled trials comparing operative and nonoperative treatment for DIACFs. DATA EXTRACTION: Information on study methods and clinical outcomes. DATA SYNTHESIS: We performed data synthesis on relevant clinical outcomes. Weighted mean differences with 95% confidence intervals were calculated for continuous data and relative risks with 95% confidence intervals were calculated for dichotomous data. A fixed-effect model or a random-effect model was used. RESULTS: Seven randomized controlled trials involving 908 patients were included. Operative treatment for DIACFs reduced problems associated with shoe wear and increased walking ability but increased the risks of overall complications and infection. There were no significant differences between the groups in American Orthopaedic Foot and Ankle Society scores, The Short Form (36) Health Survey, return to work, rate of subsequent subtalar fusion, or the rate of reflex sympathetic dystrophy. CONCLUSIONS: This meta-analysis documented that when surgery was performed correctly, better shoe wear and improved walking ability could be expected. These outcomes seemed to be based on the surgeon's ability to obtain an acceptable reduction. Benefits were tempered by the increase in wound complications associated with this intervention. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence. PMID- 26371618 TI - Relapse prevention in major depressive disorder: Mindfulness-based cognitive therapy versus an active control condition. AB - OBJECTIVE: We evaluated the comparative effectiveness of mindfulness-based cognitive therapy (MBCT) versus an active control condition (ACC) for depression relapse prevention, depressive symptom reduction, and improvement in life satisfaction. METHOD: Ninety-two participants in remission from major depressive disorder with residual depressive symptoms were randomized to either an 8-week MBCT or a validated ACC that is structurally equivalent to MBCT and controls for nonspecific effects (e.g., interaction with a facilitator, perceived social support, treatment outcome expectations). Both interventions were delivered according to their published manuals. RESULTS: Intention-to-treat analyses indicated no differences between MBCT and ACC in depression relapse rates or time to relapse over a 60-week follow-up. Both groups experienced significant and equal reductions in depressive symptoms and improvements in life satisfaction. A significant quadratic interaction (Group * Time) indicated that the pattern of depressive symptom reduction differed between groups. The ACC experienced immediate symptom reduction postintervention and then a gradual increase over the 60-week follow-up. The MBCT group experienced a gradual linear symptom reduction. The pattern for life satisfaction was identical but only marginally significant. CONCLUSIONS: MBCT did not differ from an ACC on rates of depression relapse, symptom reduction, or life satisfaction, suggesting that MBCT is no more effective for preventing depression relapse and reducing depressive symptoms than the active components of the ACC. Differences in trajectory of depressive symptom improvement suggest that the intervention-specific skills acquired may be associated with differential rates of therapeutic benefit. This study demonstrates the importance of comparing psychotherapeutic interventions to active control conditions. PMID- 26371620 TI - Bone Marrow Aspirate Concentrate in Animal Long Bone Healing: An Analysis of Basic Science Evidence. AB - OBJECTIVES: Long bone fractures that fail to heal or show a delay in healing can lead to increased morbidity. Bone marrow aspirate concentrate (BMAC) containing bone mesenchymal stem cells (BMSCs) has been suggested as an autologous biologic adjunct to aid long bone healing. The purpose of this study was to systematically review the basic science in vivo evidence for the use of BMAC with BMSCs in the treatment of segmental defects in animal long bones. DATA SOURCES: The PubMed/MEDLINE and EMBASE databases were screened in July 14-25, 2014. STUDY SELECTION: The following search criteria were used: [("bmac" OR "bone marrow aspirate concentrate" OR "bmc" OR "bone marrow concentrate" OR "mesenchymal stem cells") AND ("bone" OR "osteogenesis" OR "fracture healing" OR "nonunion" OR "delayed union")]. DATA EXTRACTION: Three authors extracted data and analyzed for trends. Quality of evidence score was given to each study. DATA SYNTHESIS: Results are presented as Hedge G standardized effect sizes with 95% confidence intervals. RESULTS: The search yielded 35 articles for inclusion. Of studies reporting statistics, 100% showed significant increase in bone formation in the BMAC group on radiograph. Ninety percent reported significant improvement in earlier bone healing on histologic/histomorphometric assessment. Eighty-one percent reported a significant increase in bone area on micro-computed tomography. Seventy-eight percent showed a higher torsional stiffness for the BMAC-treated defects. CONCLUSION: In the in vivo studies evaluated, BMAC confer beneficial effects on the healing of segmental defects in animal long bone models when compared with a control. Proof-of-concept has been established for BMAC in the treatment of animal segmental bone defects. PMID- 26371621 TI - Does Admission to Medicine or Orthopaedics Impact a Geriatric Hip Patient's Hospital Length of Stay? AB - OBJECTIVES: The aim of our study was to determine the association between admitting service, medicine or orthopaedics, and length of stay (LOS) for a geriatric hip fracture patient. DESIGN: Retrospective. SETTING: Urban level 1 trauma center. PATIENTS/PARTICIPANTS: Six hundred fourteen geriatric hip fracture patients from 2000 to 2009. INTERVENTIONS: Orthopaedic surgery for geriatric hip fracture. MAIN OUTCOME MEASUREMENTS: Patient demographics, medical comorbidities, hospitalization length, and admitting service. Negative binomial regression used to determine association between LOS and admitting service. RESULTS: Six hundred fourteen geriatric hip fracture patients were included in the analysis, of whom 49.2% of patients (n = 302) were admitted to the orthopaedic service and 50.8% (3 = 312) to the medicine service. The median LOS for patients admitted to orthopaedics was 4.5 days compared with 7 days for patients admitted to medicine (P < 0.0001). Readmission was also significantly higher for patients admitted to medicine (n = 92, 29.8%) than for those admitted to orthopaedics (n = 70, 23.1%). After controlling for important patient factors, it was determined that medicine patients are expected to stay about 1.5 times (incidence rate ratio: 1.48, P < 0.0001) longer in the hospital than orthopaedic patients. CONCLUSIONS: This is the largest study to demonstrate that admission to the medicine service compared with the orthopaedic service increases a geriatric hip fractures patient's expected LOS. Since LOS is a major driver of cost as well as a measure of quality care, it is important to understand the factors that lead to a longer hospital stay to better allocate hospital resources. Based on the results from our institution, orthopaedic surgeons should be aware that admission to medicine might increase a patient's expected LOS. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence. PMID- 26371622 TI - Biomechanics of occlusion--implications for oral rehabilitation. AB - The dental occlusion is an important aspect of clinical dentistry; there are diverse functional demands ranging from highly precise tooth contacts to large crushing forces. Further, there are dogmatic, passionate and often diverging views on the relationship between the dental occlusion and various diseases and disorders including temporomandibular disorders, non-carious cervical lesions and tooth movement. This study provides an overview of the biomechanics of the masticatory system in the context of the dental occlusion's role in function. It explores the adaptation and precision of dental occlusion, its role in bite force, jaw movement, masticatory performance and its influence on the oro-facial musculoskeletal system. Biomechanics helps us better understand the structure and function of biological systems and consequently an understanding of the forces on, and displacements of, the dental occlusion. Biomechanics provides insight into the relationships between the dentition, jaws, temporomandibular joints, and muscles. Direct measurements of tooth contacts and forces are difficult, and biomechanical models have been developed to better understand the relationship between the occlusion and function. Importantly, biomechanical research will provide knowledge to help correct clinical misperceptions and inform better patient care. The masticatory system demonstrates a remarkable ability to adapt to a changing biomechanical environment and changes to the dental occlusion or other components of the musculoskeletal system tend to be well tolerated. PMID- 26371623 TI - New clinical trials for nonmotor manifestations of Parkinson's disease. AB - Nonmotor manifestations in Parkinson's disease (PD) encompass a range of clinical features, including neuropsychiatric problems, autonomic dysfunction, sleep disorders, fatigue, and pain. Despite their importance for patients' quality of life, the evidence base for their treatment is relatively sparse. Nevertheless, the last few years have seen a number of new trials starting that specifically address nonmotor features as an outcome measure in clinical trials. Large randomized, controlled trials in the last 3 years reported improvement of psychosis with the new selective serotonin 5-HT2A inverse agonist pimavanserin and of postural hypotension with the oral norepinephrine precursor droxidopa. Smaller new randomized, controlled trials support the effectiveness of Deep Brain Stimulation and opiates for pain, of rivastigmine for apathy and piribedil for apathy post-DBS, group cognitive behavioral therapy for depression and/or anxiety, continuous positive airway pressure for sleep apnea in PD and doxepin for insomnia, and of solifenacin succinate and transcutaneous tibial nerve stimulation for urinary symptoms. A number of new smaller or open trials as well as post-hoc analyses of randomized, controlled trials have suggested usefulness of other treatments, and new randomized, controlled trials are currently ongoing. PMID- 26371624 TI - Therapeutic advances in restless legs syndrome (RLS). AB - Levodopa and dopamine agonists have been the main treatment for restless legs syndrome during the past decades. Although their efficacy has been well documented over the short term, long-term dopaminergic treatment is often complicated by augmentation, loss of efficacy, and other side effects. Recent large randomized controlled trials provide new evidence for the efficacy of high potency opioids and alpha2delta ligands, and several post hoc analyses, meta analyses, algorithms, and guidelines have been published, often with a specific focus, for example, on augmentation, or on management of restless legs syndrome during pregnancy. Several new contributions to understanding the pathophysiology of restless legs syndrome have been published, but at this time, whether they will have an impact on treatment possibilities in the future cannot be estimated. PMID- 26371625 TI - Nephrologists' management of patient medications in kidney transplantation: results of an online survey. AB - RATIONALE, AIMS AND OBJECTIVES: Medication adherence is essential in kidney transplant recipients to reduce the risk of rejection and subsequent allograft loss. The aim of this study was to delineate what 'usual care' entails, in relation to medication management, for adult kidney transplant recipients. METHODS: An online survey was developed to explore how nephrologists promote and assess medication adherence, the management of prescriptions, the frequency of clinic appointments and the frequency of clinical screening tests. Nephrologists from all acute kidney transplant units in Victoria, Australia, were invited to participate. Data were collected between May and June 2014. RESULTS: Of 60 nephrologists invited to participate, 22 completed the survey (response rate of 36.6%). Respondents had a mean age of 49.1 +/- 10.1 years, with a mean of 20.1 +/ 9.9 years working in nephrology and 14 were men. Descriptive analysis of responses showed that nephrologists performed frequent screening for kidney graft dysfunction that may indicate medication non-adherence, maintained regular transplant clinic visits with patients and emphasized the importance of medication education. However, time constraints during consultations impacted on extensive patient education and the long-term medication follow-up support was often delivered by the renal transplant nurse coordinator or pharmacist. CONCLUSIONS: This study highlighted that nephrologists took an active approach in the medication management of kidney transplant recipients, which may assist with facilitating long-term graft survival. Ultimately, promoting medication adherence needs to be patient centred, involving an interdisciplinary team of nephrologists, pharmacists and renal transplant nurse coordinators, working together with the patient to establish optimal adherence. PMID- 26371626 TI - Reaching China: potentials and pitfalls. PMID- 26371627 TI - Erratum. PMID- 26371628 TI - Synthesis and structural/physical properties of U3Fe2Ge7: a single-crystal study. AB - A single crystal of U3Fe2Ge7 was synthesized by the tin-flux method, and its structural and electronic properties were studied. The compound crystallizes in the orthorhombic crystal structure of La3Co2Sn7 type with two Wyckoff sites for the U atoms. U3Fe2Ge7 displays a ferromagnetic order below TC = 62 K. Magnetization measurements in static (up to 14 T) and pulsed (up to 60 T) magnetic fields revealed a strong two-ion uniaxial magnetic anisotropy. The easy magnetization direction is along the c axis and the spontaneous magnetic moment is 3.3 MUB per formula unit at 2 K. The moment per Fe atom is 0.2 MUB, as follows from Mossbauer spectroscopy. The magnetic moments are oriented perpendicular to the shortest inter-uranium distances that occur within the zigzag chains in the ab plane, contrary to other U-based isostructural compounds. The magnetization along the a axis reveals a first-order magnetization process that allows for a quantitative description of the magnetic anisotropy in spite of its enormous energetic strength. The strong anisotropy is reflected in the specific heat and electrical resistivity that are affected by a gap in magnon spectrum. PMID- 26371630 TI - Nucleation of NaCl from Aqueous Solution: Critical Sizes, Ion-Attachment Kinetics, and Rates. AB - Nucleation and crystal growth are important in material synthesis, climate modeling, biomineralization, and pharmaceutical formulation. Despite tremendous efforts, the mechanisms and kinetics of nucleation remain elusive to both theory and experiment. Here we investigate sodium chloride (NaCl) nucleation from supersaturated brines using seeded atomistic simulations, polymorph-specific order parameters, and elements of classical nucleation theory. We find that NaCl nucleates via the common rock salt structure. Ion desolvation-not diffusion-is identified as the limiting resistance to attachment. Two different analyses give approximately consistent attachment kinetics: diffusion along the nucleus size coordinate and reaction-diffusion analysis of approach-to-coexistence simulation data from Aragones et al. ( J. Chem. Phys. 2012, 136, 244508 ). Our simulations were performed at realistic supersaturations to enable the first direct comparison to experimental nucleation rates for this system. The computed and measured rates converge to a common upper limit at extremely high supersaturation. However, our rate predictions are between 15 and 30 orders of magnitude too fast. We comment on possible origins of the large discrepancy. PMID- 26371629 TI - Au-Ag@Au Hollow Nanostructure with Enhanced Chemical Stability and Improved Photothermal Transduction Efficiency for Cancer Treatment. AB - Despite the fact that Au-Ag hollow nanoparticles (HNPs) have gained much attention as ablation agents for photothermal therapy, the instability of the Ag element limits their applications. Herein, excess Au atoms were deposited on the surface of a Au-Ag HNP by improving the reduction power of l-ascorbic acid (AA) and thereby preventing the reaction between HAuCl4 and the Ag element in the Au Ag alloy nanostructure. Significantly, the obtained Au-Ag@Au HNPs show excellent chemical stability in an oxidative environment, together with remarkable increase in extinction peak intensity and obvious narrowing in peak width. Moreover, finite-difference time-domain (FDTD) was used to simulate the optical properties and electric field distribution of HNPs. The calculated results show that the proportion of absorption cross section in total extinction cross section increases with the improvement of Au content in HNP. As predicted by the theoretical calculation results, Au-Ag@Au nanocages (NCs) exhibit a photothermal transduction efficiency (eta) as high as 36.5% at 808 nm, which is higher than that of Au-Ag NCs (31.2%). Irradiated by 808 nm laser at power densities of 1 W/cm(2), MCF-7 breast cancer cells incubated with PEGylated Au-Ag@Au NCs were seriously destroyed. Combined together, Au-Ag@Au HNPs with enhanced chemical stability and improved photothermal transduction efficiency show superior competitiveness as photothermal agents. PMID- 26371632 TI - Vacuum Friction on a Rotating Pair of Atoms. AB - Zero-point quantum fluctuations of the electromagnetic vacuum create the widely known London-van der Waals attractive force between two atoms. Recently, there has been a revived interest in the interaction of rotating matter with the quantum vacuum. Here, we consider a rotating pair of atoms maintained by London van der Waals forces and calculate the frictional torque they experience due to zero-point radiation. Using a semiclassical framework derived from the fluctuation dissipation theorem, we take into account the full electrostatic coupling between induced dipoles. Considering the case of zero temperature only, we find a braking torque proportional to the angular velocity and to the third power of the fine structure constant. Although very small compared to London-van der Waals attraction, the torque is strong enough to induce the formation of dimers in binary collisions. This new friction phenomenon at the atomic level should induce a paradigm change in the explanation of irreversibility. PMID- 26371631 TI - Five Measurement Bases Determine Pure Quantum States on Any Dimension. AB - A long-standing problem in quantum mechanics is the minimum number of observables required for the characterization of unknown pure quantum states. The solution to this problem is especially important for the developing field of high-dimensional quantum information processing. In this work we demonstrate that any pure d dimensional state is unambiguously reconstructed by measuring five observables, that is, via projective measurements onto the states of five orthonormal bases. Thus, in our method the total number of different measurement outcomes (5d) scales linearly with d. The state reconstruction is robust against experimental errors and requires simple postprocessing, regardless of d. We experimentally demonstrate the feasibility of our scheme through the reconstruction of eight dimensional quantum states, encoded in the momentum of single photons. PMID- 26371633 TI - Classical Analog to Entanglement Reversibility. AB - In this Letter we study the problem of secrecy reversibility. This asks when two honest parties can distill secret bits from some tripartite distribution p(XYZ) and transform secret bits back into p(XYZ) at equal rates using local operation and public communication. This is the classical analog to the well-studied problem of reversibly concentrating and diluting entanglement in a quantum state. We identify the structure of distributions possessing reversible secrecy when one of the honest parties holds a binary distribution, and it is possible that all reversible distributions have this form. These distributions are more general than what is obtained by simply constructing a classical analog to the family of quantum states known to have reversible entanglement. An indispensable tool used in our analysis is a conditional form of the Gacs-Korner common information. PMID- 26371634 TI - Onsager Coefficients in Periodically Driven Systems. AB - We evaluate the Onsager matrix for a system under time-periodic driving by considering all its Fourier components. By application of the second law, we prove that all the fluxes converge to zero in the limit of zero dissipation. Reversible efficiency can never be reached at finite power. The implication for an Onsager matrix, describing reduced fluxes, is that its determinant has to vanish. In the particular case of only two fluxes, the corresponding Onsager matrix becomes symmetric. PMID- 26371635 TI - Modeling the Complete Gravitational Wave Spectrum of Neutron Star Mergers. AB - In the context of neutron star mergers, we study the gravitational wave spectrum of the merger remnant using numerical relativity simulations. Postmerger spectra are characterized by a main peak frequency f2 related to the particular structure and dynamics of the remnant hot hypermassive neutron star. We show that f(2) is correlated with the tidal coupling constant kappa(2)^T that characterizes the binary tidal interactions during the late-inspiral merger. The relation f(2)(kappa(2)^T) depends very weakly on the binary total mass, mass ratio, equation of state, and thermal effects. This observation opens up the possibility of developing a model of the gravitational spectrum of every merger unifying the late-inspiral and postmerger descriptions. PMID- 26371636 TI - Evolution and End Point of the Black String Instability: Large D Solution. AB - We derive a simple set of nonlinear, (1+1)-dimensional partial differential equations that describe the dynamical evolution of black strings and branes to leading order in the expansion in the inverse of the number of dimensions D. These equations are easily solved numerically. Their solution shows that thin enough black strings are unstable to developing inhomogeneities along their length, and at late times they asymptote to stable nonuniform black strings. This proves an earlier conjecture about the end point of the instability of black strings in a large enough number of dimensions. If the initial black string is very thin, the final configuration is highly nonuniform and resembles a periodic array of localized black holes joined by short necks. We also present the equations that describe the nonlinear dynamics of anti-de Sitter black branes at large D. PMID- 26371637 TI - First Detection of the Acoustic Oscillation Phase Shift Expected from the Cosmic Neutrino Background. AB - The unimpeded relativistic propagation of cosmological neutrinos prior to recombination of the baryon-photon plasma alters gravitational potentials and therefore the details of the time-dependent gravitational driving of acoustic oscillations. We report here a first detection of the resulting shifts in the temporal phase of the oscillations, which we infer from their signature in the cosmic microwave background temperature power spectrum. PMID- 26371639 TI - String Theory Origin of Dyonic N=8 Supergravity and Its Chern-Simons Duals. AB - We clarify the higher-dimensional origin of a class of dyonic gaugings of D=4 N=8 supergravity recently discovered, when the gauge group is chosen to be ISO(7). This dyonically gauged maximal supergravity arises from consistent truncation of massive IIA supergravity on S^6, and its magnetic coupling constant descends directly from the Romans mass. The critical points of the supergravity uplift to new four-dimensional anti-de Sitter space (AdS4) massive type IIA vacua. We identify the corresponding three-dimensional conformal field theory (CFT3) duals as super-Chern-Simons-matter theories with simple gauge group SU(N) and level k given by the Romans mass. In particular, we find a critical point that uplifts to the first explicit N=2 AdS4 massive IIA background. We compute its free energy and that of the candidate dual Chern-Simons theory by localization to a solvable matrix model, and find perfect agreement. This provides the first AdS4/CFT3 precision match in massive type IIA string theory. PMID- 26371638 TI - Search for Event Rate Modulation in XENON100 Electronic Recoil Data. AB - We have searched for periodic variations of the electronic recoil event rate in the (2-6) keV energy range recorded between February 2011 and March 2012 with the XENON100 detector, adding up to 224.6 live days in total. Following a detailed study to establish the stability of the detector and its background contributions during this run, we performed an unbinned profile likelihood analysis to identify any periodicity up to 500 days. We find a global significance of less than 1sigma for all periods, suggesting no statistically significant modulation in the data. While the local significance for an annual modulation is 2.8sigma, the analysis of a multiple-scatter control sample and the phase of the modulation disfavor a dark matter interpretation. The DAMA/LIBRA annual modulation interpreted as a dark matter signature with axial-vector coupling of weakly interacting massive particles to electrons is excluded at 4.8sigma. PMID- 26371641 TI - Condensed State of Heavy Vectorlike Neutrinos. AB - Some extensions of the standard model suggest the existence of vectorlike fermions whose mass M can be larger by up to several orders of magnitude than the electroweak scale v, and with the Higgs mechanism providing only a small part m of this mass that is a fraction of v. It is shown that in a certain range of the parameters m and M, there exist stable globules of degenerate fermionic matter made from the lighter of the neutral vectorlike leptons (superheavy neutrinos) with a number density much larger than m(h)v(2), with m(h) being the Higgs boson mass. The stability is due to the deformation of the Higgs field inside the globule to values greatly exceeding v. The globules are absolutely stable if the lighter of the vectorlike neutrinos is stable and can be (a part of) the dark matter. PMID- 26371643 TI - Neutrino Production of a Charmed Meson and the Transverse Spin Structure of the Nucleon. AB - We calculate the amplitude for exclusive neutrino production of a charmed meson on an unpolarized target in the collinear QCD approach, where generalized parton distributions (GPDs) factorize from perturbatively calculable coefficient functions. We demonstrate that the transversity chiral odd GPDs contribute to the transverse cross section if the hard amplitude is calculated up to order m_{c}/Q. We show how to access these GPDs through the azimuthal dependence of the nuN >MU^{-}D^{+}N differential cross section. PMID- 26371645 TI - High-Precision Determination of the Pion-Nucleon sigma Term from Roy-Steiner Equations. AB - We present a determination of the pion-nucleon (piN) sigma term sigma_{piN} based on the Cheng-Dashen low-energy theorem (LET), taking advantage of the recent high precision data from pionic atoms to pin down the piN scattering lengths as well as of constraints from analyticity, unitarity, and crossing symmetry in the form of Roy-Steiner equations to perform the extrapolation to the Cheng-Dashen point in a reliable manner. With isospin-violating corrections included both in the scattering lengths and the LET, we obtain sigma_{piN}=(59.1+/-1.9+/-3.0) MeV=(59.1+/-3.5) MeV, where the first error refers to uncertainties in the piN amplitude and the second to the LET. Consequences for the scalar nucleon couplings relevant for the direct detection of dark matter are discussed. PMID- 26371646 TI - Optimized Effective Potential for Quantum Electrodynamical Time-Dependent Density Functional Theory. AB - We propose an orbital exchange-correlation functional for applying time-dependent density functional theory to many-electron systems coupled to cavity photons. The time nonlocal equation for the electron-photon optimized effective potential (OEP) is derived. In the static limit our OEP energy functional reduces to the Lamb shift of the ground state energy. We test the new approximation in the Rabi model. It is shown that the OEP (i) reproduces quantitatively the exact ground state energy from the weak to the deep strong coupling regime and (ii) accurately captures the dynamics entering the ultrastrong coupling regime. The present formalism opens the path to a first-principles description of correlated electron photon systems, bridging the gap between electronic structure methods and quantum optics for real material applications. PMID- 26371647 TI - Correlated Exciton Transport in Rydberg-Dressed-Atom Spin Chains. AB - We investigate the transport of excitations through a chain of atoms with nonlocal dissipation introduced through coupling to additional short-lived states. The system is described by an effective spin-1/2 model where the ratio of the exchange interaction strength to the reservoir coupling strength determines the type of transport, including coherent exciton motion, incoherent hopping, and a regime in which an emergent length scale leads to a preferred hopping distance far beyond nearest neighbors. For multiple impurities, the dissipation gives rise to strong nearest-neighbor correlations and entanglement. These results highlight the importance of nontrivial dissipation, correlations, and many-body effects in recent experiments on the dipole-mediated transport of Rydberg excitations. PMID- 26371648 TI - Mechanism and Experimental Observability of Global Switching Between Reactive and Nonreactive Coordinates at High Total Energies. AB - We present a mechanism of global reaction coordinate switching, namely, a phenomenon in which the reaction coordinate dynamically switches to another coordinate as the total energy of the system increases. The mechanism is based on global changes in the underlying phase space geometry caused by a switching of dominant unstable modes from the original reactive mode to another nonreactive mode in systems with more than 2 degrees of freedom. We demonstrate an experimental observability to detect a reaction coordinate switching in an ionization reaction of a hydrogen atom in crossed electric and magnetic fields. For this reaction, the reaction coordinate is a coordinate along which electrons escape and its switching changes the escaping direction from the direction of the electric field to that of the magnetic field and, thus, the switching can be detected experimentally by measuring the angle-resolved momentum distribution of escaping electrons. PMID- 26371649 TI - Resonant Charge Transfer of Hydrogen Rydberg Atoms Incident on a Cu(100) Projected Band-Gap Surface. AB - The charge transfer (ionization) of hydrogen Rydberg atoms (n=25-34) incident on a Cu(100) surface is investigated. Unlike fully metallic surfaces, where the Rydberg electron energy is degenerate with the conduction band of the metal, the Cu(100) surface has a projected band gap at these energies, and only discrete image states are available through which charge transfer can take place. Resonant enhancement of charge transfer is observed for Rydberg states whose energy matches one of the image states, and the integrated surface ionization signals (signal versus applied field) show clear periodicity as a function of n as the energies come in and out of resonance with the image states. The surface ionization dynamics show a velocity dependence; decreased velocity of the incident H atom leads to a greater mean distance of ionization and a lower field required to extract the ion. The surface ionization profiles for "on resonance" n values show a changing shape as the velocity is changed, reflecting the finite field range over which resonance occurs. PMID- 26371650 TI - Coherence and Rydberg Blockade of Atomic Ensemble Qubits. AB - We demonstrate |W? state encoding of multiatom ensemble qubits. Using optically trapped Rb atoms, the T_{2} coherence time is 2.6(3) ms for N[over -]=7.6 atoms and scales approximately inversely with the number of atoms. Strong Rydberg blockade between two ensemble qubits is demonstrated with a fidelity of 0.89(1), and with a fidelity of ~1.0 when postselected on a control ensemble excitation. These results are a significant step towards deterministic entanglement of atomic ensembles. PMID- 26371651 TI - All-Optical Preparation of Coherent Dark States of a Single Rare Earth Ion Spin in a Crystal. AB - All-optical addressing and coherent control of single solid-state based quantum bits is a key tool for fast and precise control of ground-state spin qubits. So far, all-optical addressing of qubits was demonstrated only in a very few systems, such as color centers and quantum dots. Here, we perform high-resolution spectroscopic of native and implanted single rare earth ions in solid, namely, a cerium ion in yttrium aluminum garnet (YAG) crystal. We find narrow and spectrally stable optical transitions between the spin sublevels of the ground and excited optical states. Utilizing these transitions we demonstrate the generation of a coherent dark state in electron spin sublevels of a single Ce^{3+} ion in YAG by coherent population trapping. PMID- 26371652 TI - Strong Coupling between a Trapped Single Atom and an All-Fiber Cavity. AB - We demonstrate an all-fiber cavity quantum electrodynamics system with a trapped single atom in the strong coupling regime. We use a nanofiber Fabry-Perot cavity, that is, an optical nanofiber sandwiched by two fiber-Bragg-grating mirrors. Measurements of the cavity transmission spectrum with a single atom in a state insensitive nanofiber trap clearly reveal the vacuum Rabi splitting. PMID- 26371653 TI - Heisenberg-Limited Qubit Read-Out with Two-Mode Squeezed Light. AB - We show how to use two-mode squeezed light to exponentially enhance cavity-based dispersive qubit measurement. Our scheme enables true Heisenberg-limited scaling of the measurement, and crucially, it is not restricted to small dispersive couplings or unrealistically long measurement times. It involves coupling a qubit dispersively to two cavities and making use of a symmetry in the dynamics of joint cavity quadratures (a so-called quantum-mechanics-free subsystem). We discuss the basic scaling of the scheme and its robustness against imperfections, as well as a realistic implementation in circuit quantum electrodynamics. PMID- 26371654 TI - Spatial Rogue Waves in Photorefractive Ferroelectrics. AB - Rogue waves are observed as light propagates in the extreme nonlinear regime that occurs when a photorefractive ferroelectric crystal is undergoing a structural phase transition. The transmitted spatial light distribution contains bright localized spots of anomalously large intensity that follow a signature long-tail statistics that disappears as the nonlinearity is weakened. The isolated wave events form as out-of-equilibrium response and disorder enhance the Kerr saturated nonlinearity at the critical point. Self-similarity associable to the individual observed filaments and numerical simulations of the generalized nonlinear Schrodinger equation suggests that dynamics of soliton fusions and scale invariance can microscopically play an important role in the observed rogue intensities and statistics. PMID- 26371655 TI - Bridging Three Orders of Magnitude: Multiple Scattered Waves Sense Fractal Microscopic Structures via Dispersion. AB - Wave scattering provides profound insight into the structure of matter. Typically, the ability to sense microstructure is determined by the ratio of scatterer size to probing wavelength. Here, we address the question of whether macroscopic waves can report back the presence and distribution of microscopic scatterers despite several orders of magnitude difference in scale between wavelength and scatterer size. In our analysis, monosized hard scatterers 5 MUm in radius are immersed in lossless gelatin phantoms to investigate the effect of multiple reflections on the propagation of shear waves with millimeter wavelength. Steady-state monochromatic waves are imaged in situ via magnetic resonance imaging, enabling quantification of the phase velocity at a voxel size big enough to contain thousands of individual scatterers, but small enough to resolve the wavelength. We show in theory, experiments, and simulations that the resulting coherent superposition of multiple reflections gives rise to power-law dispersion at the macroscopic scale if the scatterer distribution exhibits apparent fractality over an effective length scale that is comparable to the probing wavelength. Since apparent fractality is naturally present in any random medium, microstructure can thereby leave its fingerprint on the macroscopically quantifiable power-law exponent. Our results are generic to wave phenomena and carry great potential for sensing microstructure that exhibits intrinsic fractality, such as, for instance, vasculature. PMID- 26371656 TI - Luminescence from Collapsing Centimeter Bubbles Expanded by Chemical Reaction. AB - We report on a new method for realizing an exceptionally strong inertial confinement of a gas in a liquid: A centimetric spherical bubble filled with a reactive gaseous mixture in a liquid is expanded by an exothermic chemical reaction whose products condense in the liquid at the bubble wall. Hence, the cavity formed in this way is essentially empty as it collapses. The temperatures reached at maximum compression, inferred from the cavity radius dynamics and further confirmed by spectroscopic measurements exceed 20 000 K. Because the cavity is typically big, our findings also provide unique space and time resolved sequences of the events accompanying the collapse, notably the development of the inertial instability notoriously known to deter strong compression. PMID- 26371658 TI - Spectral Modification of Shock Accelerated Ions Using a Hydrodynamically Shaped Gas Target. AB - We report on reproducible shock acceleration from irradiation of a lambda=10 MUm CO_{2} laser on optically shaped H_{2} and He gas targets. A low energy laser prepulse (I?10^{14} W cm^{-2}) is used to drive a blast wave inside the gas target, creating a steepened, variable density gradient. This is followed, after 25 ns, by a high intensity laser pulse (I>10^{16} W cm^{-2}) that produces an electrostatic collisionless shock. Upstream ions are accelerated for a narrow range of prepulse energies. For long density gradients (?40 MUm), broadband beams of He^{+} and H^{+} are routinely produced, while for shorter gradients (?20 MUm), quasimonoenergetic acceleration of protons is observed. These measurements indicate that the properties of the accelerating shock and the resultant ion energy distribution, in particular the production of narrow energy spread beams, is highly dependent on the plasma density profile. These findings are corroborated by 2D particle-in-cell simulations. PMID- 26371659 TI - Self-Organizing Knotted Magnetic Structures in Plasma. AB - We perform full-magnetohydrodynamics simulations on various initially helical configurations and show that they reconfigure into a state where the magnetic field lines span nested toroidal surfaces. This relaxed configuration is not a Taylor state, as is often assumed for relaxing plasma, but a state where the Lorentz force is balanced by the hydrostatic pressure, which is lowest on the central ring of the nested tori. Furthermore, the structure is characterized by a spatially slowly varying rotational transform, which leads to the formation of a few magnetic islands at rational surfaces. We then obtain analytic expressions that approximate the global structure of the quasistable linked and knotted plasma configurations that emerge, using maps from S^{3} to S^{2} of which the Hopf fibration is a special case. The knotted plasma configurations have a highly localized magnetic energy density and retain their structure on time scales much longer than the Alfvenic time scale. PMID- 26371660 TI - Spontaneous Decay of Periodic Magnetostatic Equilibria. AB - In order to understand the conditions that lead to a highly magnetized, relativistic plasma becoming unstable, and in such cases how the plasma evolves, we study a prototypical class of magnetostatic equilibria in which the magnetic field satisfies ?*B=alphaB, where alpha is spatially uniform, on a periodic domain. Using numerical solutions, we show that generic examples of such equilibria are unstable to ideal modes (including incompressible ones), which are marked by exponential growth in the linear phase. We characterize the unstable mode, showing how it can be understood in terms of merging magnetic and current structures, and explicitly demonstrate its instability using the energy principle. Following the nonlinear evolution of these solutions, we find that they rapidly develop regions with relativistic velocities and electric fields of comparable magnitude to the magnetic field, liberating magnetic energy on dynamical time scales and eventually settling into a configuration with the largest allowable wavelength. These properties make such solutions a promising setting for exploring the mechanisms behind extreme cosmic sources of gamma rays. PMID- 26371661 TI - Diffraction-Unlimited Position Measurement of Ultracold Atoms in an Optical Lattice. AB - We consider a method of high-fidelity, spatially resolved position measurement of ultracold atoms in an optical lattice. We show that the atom-number distribution can be nondestructively determined at a spatial resolution beyond the diffraction limit by tracking the progressive evolution of the many-body wave function collapse into a Fock state. We predict that the Pauli exclusion principle accelerates the rate of wave function collapse of fermions in comparison with bosons. A possible application of our principle of surpassing the diffraction limit to other imaging systems is discussed. PMID- 26371662 TI - Charge Pumping of Interacting Fermion Atoms in the Synthetic Dimension. AB - Recently it has been theoretically proposed and experimentally demonstrated that a spin-orbit coupled multicomponent gas in a 1D lattice can be viewed as a spinless gas in a synthetic 2D lattice with a magnetic flux. In this Letter we consider interaction effects in such a Fermi gas, and propose these effects can be easily detected in a charge pumping experiment. Using 1/3 filling of the lowest 2D band as an example, in the strongly interacting regime, we show that the charge pumping value gradually approaches a universal fractional value for large spin components and low filling of the 1D lattice, indicating a fractional quantum Hall-type behavior, while the charge pumping value is zero if the 1D lattice filling is commensurate, indicating a Mott insulator behavior. The charge density-wave order is also discussed. PMID- 26371657 TI - New Method for a Continuous Determination of the Spin Tune in Storage Rings and Implications for Precision Experiments. AB - A new method to determine the spin tune is described and tested. In an ideal planar magnetic ring, the spin tune-defined as the number of spin precessions per turn-is given by nu(s)=gammaG (gamma is the Lorentz factor, G the gyromagnetic anomaly). At 970 MeV/c, the deuteron spins coherently precess at a frequency of ~120 kHz in the Cooler Synchrotron COSY. The spin tune is deduced from the up down asymmetry of deuteron-carbon scattering. In a time interval of 2.6 s, the spin tune was determined with a precision of the order 10^{-8}, and to 1*10^{-10} for a continuous 100 s accelerator cycle. This renders the presented method a new precision tool for accelerator physics; controlling the spin motion of particles to high precision is mandatory, in particular, for the measurement of electric dipole moments of charged particles in a storage ring. PMID- 26371663 TI - Direct Observation of Melting in Shock-Compressed Bismuth With Femtosecond X-ray Diffraction. AB - The melting of bismuth in response to shock compression has been studied using in situ femtosecond x-ray diffraction at an x-ray free electron laser. Both solid solid and solid-liquid phase transitions are documented using changes in discrete diffraction peaks and the emergence of broad, liquid scattering upon release from shock pressures up to 14 GPa. The transformation from the solid state to the liquid is found to occur in less than 3 ns, very much faster than previously believed. These results are the first quantitative measurements of a liquid material obtained on shock release using x-ray diffraction, and provide an upper limit for the time scale of melting of bismuth under shock loading. PMID- 26371664 TI - Growth of Metal Phthalocyanine on Deactivated Semiconducting Surfaces Steered by Selective Orbital Coupling. AB - Using scanning tunneling microscopy and density functional theory, we show that the molecular ordering and orientation of metal phthalocyanine molecules on the deactivated Si surface display a strong dependency on the central transition metal ion, driven by the degree of orbital hybridization at the heterointerface via selective p-d orbital coupling. This Letter identifies a selective mechanism for modifying the molecule-substrate interaction which impacts the growth behavior of transition-metal-incorporated organic molecules on a technologically relevant substrate for silicon-based devices. PMID- 26371642 TI - Observation and Spin-Parity Determination of the X(1835) in J/psi >gammaK_{S}^{0}K_{S}^{0}eta. AB - We report an observation of the process J/psi->gammaX(1835) >gammaK_{S}^{0}K_{S}^{0}eta at low K_{S}^{0}K_{S}^{0} mass with a statistical significance larger than 12.9sigma using a data sample of 1.31*10^{9} J/psi events collected with the BESIII detector. In this region of phase space the K_{S}^{0}K_{S}^{0} system is dominantly produced through the f_{0}(980). By performing a partial wave analysis, we determine the spin parity of the X(1835) to be J^{PC}=0^{-+}. The mass and width of the observed X(1835) are 1844+/ 9(stat)_{-25}^{+16}(syst) MeV/c^{2} and 192_{-17}^{+20}(stat)_{-43}^{+62}(syst) MeV, respectively, which are consistent with the results obtained by BESIII in the channel J/psi->gammapi^{+}pi^{-}eta^{'}. PMID- 26371665 TI - Nature of the Insulating Ground State of the 5d Postperovskite CaIrO3. AB - The insulating ground state of the 5d transition metal oxide CaIrO3 has been classified as a Mott-type insulator. Based on a systematic density functional theory (DFT) study with local, semilocal, and hybrid exchange-correlation functionals, we reveal that the Ir t(2g) states exhibit large splittings and one dimensional electronic states along the c axis due to a tetragonal crystal field. Our hybrid DFT calculation adequately describes the antiferromagnetic (AFM) order along the c direction via a superexchange interaction between Ir^{4+} spins. Furthermore, the spin-orbit coupling (SOC) hybridizes the t(2g) states to open an insulating gap. These results indicate that CaIrO_{3} can be represented as a spin-orbit Slater insulator, driven by the interplay between a long-range AFM order and the SOC. Such a Slater mechanism for the gap formation is also demonstrated by the DFT + dynamical mean field theory calculation, where the metal-insulator transition and the paramagnetic to AFM phase transition are concomitant with each other. PMID- 26371666 TI - Magnetism of Gadolinium: A First-Principles Perspective. AB - By calculating the spectral density of states in the ferromagnetic ground state and in the high temperature paramagnetic phase we provide the first concise study of finite temperature effects on the electronic structure of the bulk and the surface of gadolinium metal. The variation of calculated spectral properties of the Fermi surface and the density of states in the bulk and at the surface are in good agreement with recent photoemission experiments performed in both ferromagnetic and paramagnetic phases. In the paramagnetic state we find vanishing spin splitting of the conduction band, but finite local spin moments both in bulk and at the surface. We clearly demonstrate that the formation of these local spin moments in the conduction band is due to the asymmetry of the density of states in the two spin channels, suggesting a complex, non-Stoner behavior. We, therefore, suggest that the vanishing or nearly vanishing spin splitting of spectral features cannot be used as an indicator for Stoner-like magnetism. PMID- 26371667 TI - Absence of Orthogonality Catastrophe after a Spatially Inhomogeneous Interaction Quench in Luttinger Liquids. AB - We investigate the Loschmidt echo, the overlap of the initial and final wave functions of Luttinger liquids after a spatially inhomogeneous interaction quench. In studying the Luttinger model, we obtain an analytic solution of the bosonic Bogoliubov-de Gennes equations after quenching the interactions within a finite spatial region. As opposed to the power-law temporal decay following a potential quench, the interaction quench in the Luttinger model leads to a finite, hardly time-dependent overlap; therefore, no orthogonality catastrophe occurs. The steady state value of the Loschmidt echo after a sudden inhomogeneous quench is the square of the respective adiabatic overlaps. Our results are checked and validated numerically on the XXZ Heisenberg chain. PMID- 26371668 TI - Electron-Phonon Coupling in the Bulk of Anatase TiO2 Measured by Resonant Inelastic X-Ray Spectroscopy. AB - We investigate the polaronic ground state of anatase TiO2 by bulk-sensitive resonant inelastic x-ray spectroscopy (RIXS) at the Ti L3 edge. We find that the formation of the polaron cloud involves a single 95 meV phonon along the c axis, in addition to the 108 meV ab-plane mode previously identified by photoemission. The coupling strength to both modes is the same within error bars, and it is unaffected by the carrier density. These data establish RIXS as a directional bulk-sensitive probe of electron-phonon coupling in solids. PMID- 26371669 TI - Formation and Observation of a Quasi-Two-Dimensional dxy Electron Liquid in Epitaxially Stabilized Sr(2-x)La(x)TiO4 Thin Films. AB - We report the formation and observation of an electron liquid in Sr(2 x)La(x)TiO4, the quasi-two-dimensional counterpart of SrTiO3, through reactive molecular-beam epitaxy and in situ angle-resolved photoemission spectroscopy. The lowest lying states are found to be comprised of Ti 3d_{xy} orbitals, analogous to the LaAlO3/SrTiO3 interface and exhibit unusually broad features characterized by quantized energy levels and a reduced Luttinger volume. Using model calculations, we explain these characteristics through an interplay of disorder and electron-phonon coupling acting cooperatively at similar energy scales, which provides a possible mechanism for explaining the low free carrier concentrations observed at various oxide heterostructures such as the LaAlO3/SrTiO3 interface. PMID- 26371670 TI - X-ray Detection of Transient Magnetic Moments Induced by a Spin Current in Cu. AB - We have used a MHz lock-in x-ray spectromicroscopy technique to directly detect changes in magnetic moment of Cu due to spin injection from an adjacent Co layer. The elemental and chemical specificity of x rays allows us to distinguish two spin current induced effects. We detect the creation of transient magnetic moments of 3*10^{-5}MU_{B} on Cu atoms within the bulk of the 28 nm thick Cu film due to spin accumulation. The moment value is compared to predictions by Mott's two current model. We also observe that the hybridization induced existing magnetic moments at the Cu interface atoms are transiently increased by about 10% or 4*10^{-3}MU_{B} per atom. This reveals the dominance of spin-torque alignment over Joule heat induced disorder of the interfacial Cu moments during current flow. PMID- 26371671 TI - Length Scale of the Spin Seebeck Effect. AB - We investigate the origin of the spin Seebeck effect in yttrium iron garnet (YIG) samples for film thicknesses from 20 nm to 50 MUm at room temperature and 50 K. Our results reveal a characteristic increase of the longitudinal spin Seebeck effect amplitude with the thickness of the insulating ferrimagnetic YIG, which levels off at a critical thickness that increases with decreasing temperature. The observed behavior cannot be explained as an interface effect or by variations of the material parameters. Comparison to numerical simulations of thermal magnonic spin currents yields qualitative agreement for the thickness dependence resulting from the finite magnon propagation length. This allows us to trace the origin of the observed signals to genuine bulk magnonic spin currents due to the spin Seebeck effect ruling out an interface origin and allowing us to gauge the reach of thermally excited magnons in this system for different temperatures. At low temperature, even quantitative agreement with the simulations is found. PMID- 26371672 TI - Quantum Manipulation of Two-Electron Spin States in Isolated Double Quantum Dots. AB - We studied experimentally the dynamics of the exchange interaction between two antiparallel electron spins in an isolated double quantum dot where coupling to the electron reservoirs can be ignored. We demonstrate that the level of control of such a double dot is higher than in conventional double dots. In particular, it allows us to couple coherently two electron spins in an efficient manner following a scheme initially proposed by Loss and DiVincenzo [Phys. Rev. A 57, 120 (1998)]. The present study demonstrates that isolated quantum dots are a possible route to increase the number of coherently coupled quantum dots. PMID- 26371673 TI - Spin-Based Mach-Zehnder Interferometry in Topological Insulator p-n Junctions. AB - Transport in three-dimensional topological insulators relies on the existence of a spin-momentum locked surface state that encloses the insulating bulk. In this work we show how, in a topological insulator p-n junction, a magnetic field turns this surface state into an electronic Mach-Zehnder interferometer. Transmission of the junction can be tuned from zero to unity, resulting in virtually perfect visibility of the interference pattern, and the reflected and transmitted currents carry opposite spin polarization so that the junction also acts as a spin filter. Our setup therefore realizes a novel and highly tunable spintronic device where the effects of spin-momentum locking in topological insulator surface states can be probed directly in a transport experiment. PMID- 26371674 TI - Andreev-Bragg Reflection from an Amperian Superconductor. AB - We show how an electrical measurement can detect the pairing of electrons on the same side of the Fermi surface (Amperian pairing), recently proposed by Patrick Lee for the pseudogap phase of high-Tc cuprate superconductors. Bragg scattering from the pair-density wave introduces odd multiples of 2k(F) momentum shifts when an electron incident from a normal metal is Andreev reflected as a hole. These Andreev-Bragg reflections can be detected in a three-terminal device, containing a ballistic Y junction between normal leads (1, 2) and the superconductor. The cross-conductance dI1/dV2 has the opposite sign for Amperian pairing than it has either in the normal state or for the usual BCS pairing. PMID- 26371675 TI - First-Principles Calculation of the Real-Space Order Parameter and Condensation Energy Density in Phonon-Mediated Superconductors. AB - We show that the superconducting order parameter and condensation energy density of phonon-mediated superconductors can be calculated in real space from first principles density functional theory for superconductors. This method highlights the connection between the chemical bonding structure and the superconducting condensation and reveals new and interesting properties of superconducting materials. Understanding this connection is essential to describe nanostructured superconducting systems where the usual reciprocal space analysis hides the basic physical mechanism. In a first application we present results for MgB2, CaC6 and hole-doped graphane. PMID- 26371676 TI - All-Electric Access to the Magnetic-Field-Invariant Magnetization of Antiferromagnets. AB - The rich physics of thin film antiferromagnets can be harnessed for prospective spintronic devices given that all-electric assessment of the tiny uncompensated magnetic moment is achieved. On the example of magnetoelectric antiferromagnetic Cr2O3, we prove that spinning-current anomalous Hall magnetometry serves as an all-electric method to probe the field-invariant uncompensated magnetization of antiferromagnets. We obtain direct access to the surface magnetization of magnetoelectric antiferromagnets providing a read-out method for ferromagnet-free magnetoelectric memory. Owing to the great sensitivity, the technique bears a strong potential to address the physics of antiferromagnets. Exemplarily, we apply the method to access the criticality of the magnetic transition for an antiferromagnetic thin film. We reveal the presence of field-invariant uncompensated magnetization even in 6-nm-thin IrMn films and clearly distinguish two contributions, of which only the minor one is involved in interfacial magnetic coupling. This approach is likely to advance the fundamental understanding of the anomalous Hall and magnetic proximity effects. PMID- 26371644 TI - Precision Measurement of the Longitudinal Double-Spin Asymmetry for Inclusive Jet Production in Polarized Proton Collisions at sqrt[s]=200 GeV. AB - We report a new measurement of the midrapidity inclusive jet longitudinal double spin asymmetry, A_{LL}, in polarized pp collisions at center-of-mass energy sqrt[s]=200 GeV. The STAR data place stringent constraints on polarized parton distribution functions extracted at next-to-leading order from global analyses of inclusive deep-inelastic scattering (DIS), semi-inclusive DIS, and RHIC pp data. The measured asymmetries provide evidence at the 3sigma level for positive gluon polarization in the Bjorken-x region x>0.05. PMID- 26371677 TI - Candidate Quantum Spin Liquid in the Ce3+ Pyrochlore Stannate Ce2Sn2O7. AB - We report the low-temperature magnetic properties of Ce2Sn2O7, a rare-earth pyrochlore. Our susceptibility and magnetization measurements show that due to the thermal isolation of a Kramers doublet ground state, Ce2Sn2O7 has Ising-like magnetic moments of ~1.18 MU_{B}. The magnetic moments are confined to the local trigonal axes, as in a spin ice, but the exchange interactions are antiferromagnetic. Below 1 K, the system enters a regime with antiferromagnetic correlations. In contrast to predictions for classical ?111?-Ising spins on the pyrochlore lattice, there is no sign of long-range ordering down to 0.02 K. Our results suggest that Ce2Sn2O7 features an antiferromagnetic liquid ground state with strong quantum fluctuations. PMID- 26371678 TI - Band Structure of Helimagnons in MnSi Resolved by Inelastic Neutron Scattering. AB - A magnetic helix realizes a one-dimensional magnetic crystal with a period given by the pitch length lambdah. Its spin-wave excitations-the helimagnons-experience Bragg scattering off this periodicity, leading to gaps in the spectrum that inhibit their propagation along the pitch direction. Using high-resolution inelastic neutron scattering, the resulting band structure of helimagnons was resolved by preparing a single crystal of MnSi in a single magnetic-helix domain. At least five helimagnon bands could be identified that cover the crossover from flat bands at low energies with helimagnons basically localized along the pitch direction to dispersing bands at higher energies. In the low-energy limit, we find the helimagnon spectrum to be determined by a universal, parameter-free theory. Taking into account corrections to this low-energy theory, quantitative agreement is obtained in the entire energy range studied with the help of a single fitting parameter. PMID- 26371679 TI - Static Magnetic Proximity Effect in Pt/NiFe2O4 and Pt/Fe Bilayers Investigated by X-Ray Resonant Magnetic Reflectivity. AB - The spin polarization of Pt in Pt/NiFe2O4 and Pt/Fe bilayers is studied by interface-sensitive x-ray resonant magnetic reflectivity to investigate static magnetic proximity effects. The asymmetry ratio of the reflectivity is measured at the Pt L3 absorption edge using circular polarized x-rays for opposite directions of the magnetization at room temperature. The results of the 2% asymmetry ratio for Pt/Fe bilayers are independent of the Pt thickness between 1.8 and 20 nm. By comparison with ab initio calculations, the maximum magnetic moment per spin polarized Pt atom at the interface is determined to be (0.6+/ 0.1) MUB for Pt/Fe. For Pt/NiFe2O4 the asymmetry ratio drops below the sensitivity limit of 0.02 MUB per Pt atom. Therefore, we conclude, that the longitudinal spin Seebeck effect recently observed in Pt/NiFe2O4 is not influenced by a proximity induced anomalous Nernst effect. PMID- 26371680 TI - Critical Thickness for Antiferroelectricity in PbZrO3. AB - Ferroelectrics and antiferroelectrics appear to have just the opposite behavior upon scaling down. Below a critical thickness of just a few nanometers the ferroelectric phase breaks into nanodomains that mimic electric properties of antiferroelectrics very closely. On the other hand, antiferroelectric thin films were found to transition from the antiferroelectric behavior to a ferroelectric one under certain growth conditions. At present, the origin of such a transition is controversial. Here, we use accurate first-principles-based finite-temperature simulations to predict the existence of a critical thickness for antiferroelectricity in the most celebrated antiferroelectric, PbZrO3. The origin of this effect is traced to the intrinsic surface contribution that has been previously overlooked. The existence of a critical thickness below which the antiferroelectric phase is replaced with a ferroelectric one not only complements the discovery of a critical thickness for ferroelectricity, but also suggests that ferroelectricity and antiferroelectricity are just two opposite manifestations of the same phenomenon: the material's tendency to develop a long range order. Nanoscaling offers the opportunity to manipulate this order. PMID- 26371681 TI - Classical Liquids in Fractal Dimension. AB - We introduce fractal liquids by generalizing classical liquids of integer dimensions d=1,2,3 to a noninteger dimension dl. The particles composing the liquid are fractal objects and their configuration space is also fractal, with the same dimension. Realizations of our generic model system include microphase separated binary liquids in porous media, and highly branched liquid droplets confined to a fractal polymer backbone in a gel. Here, we study the thermodynamics and pair correlations of fractal liquids by computer simulation and semianalytical statistical mechanics. Our results are based on a model where fractal hard spheres move on a near-critical percolating lattice cluster. The predictions of the fractal Percus-Yevick liquid integral equation compare well with our simulation results. PMID- 26371682 TI - Ferromagnetic Switching of Knotted Vector Fields in Liquid Crystal Colloids. AB - We experimentally realize polydomain and monodomain chiral ferromagnetic liquid crystal colloids that exhibit solitonic and knotted vector field configurations. Formed by dispersions of ferromagnetic nanoplatelets in chiral nematic liquid crystals, these colloidal ferromagnets exhibit spontaneous long-range alignment of magnetic dipole moments of individual platelets, giving rise to a continuum of the magnetization field M(r). Competing effects of surface confinement and chirality prompt spontaneous formation and enable the optical generation of localized twisted solitonic structures with double-twist tubes and torus knots of M(r), which exhibit a strong sensitivity to the direction of weak magnetic fields ~1 mT. Numerical modeling, implemented through free energy minimization to arrive at a field-dependent three-dimensional M(r), shows a good agreement with experiments and provides insights into the torus knot topology of observed field configurations and the corresponding physical underpinnings. PMID- 26371683 TI - Divergence of Viscosity in Jammed Granular Materials: A Theoretical Approach. AB - A theory for jammed granular materials is developed with the aid of a nonequilibrium steady-state distribution function. The approximate nonequilibrium steady-state distribution function is explicitly given in the weak dissipation regime by means of the relaxation time. The theory quantitatively agrees with the results of the molecular dynamics simulation on the critical behavior of the viscosity below the jamming point without introducing any fitting parameter. PMID- 26371684 TI - Transitions between Spatial Attractors in Place-Cell Models. AB - The spontaneous transitions between D-dimensional spatial maps in an attractor neural network are studied. Two scenarios for the transition from one map to another are found, depending on the level of noise: (i) through a mixed state, partly localized in both maps around positions where the maps are most similar, and (ii) through a weakly localized state in one of the two maps, followed by a condensation in the arrival map. Our predictions are confirmed by numerical simulations and qualitatively compared to recent recordings of hippocampal place cells during quick-environment-changing experiments in rats. PMID- 26371686 TI - Measurement of Stress Redistribution in Flowing Emulsions. AB - We study how local rearrangements alter droplet stresses within flowing dense quasi-two-dimensional emulsions at area fractions phi>=0.88. Using microscopy, we measure droplet positions while simultaneously using their deformed shape to measure droplet stresses. We find that rearrangements alter nearby stresses in a quadrupolar pattern: stresses on neighboring droplets tend to either decrease or increase depending on location. The stress redistribution is more anisotropic with increasing phi. The spatial character of the stress redistribution influences where subsequent rearrangements occur. Our results provide direct quantitative support for rheological theories of dense amorphous materials that connect local rearrangements to changes in nearby stress. PMID- 26371685 TI - Negative Interfacial Tension in Phase-Separated Active Brownian Particles. AB - We study numerically a model for active suspensions of self-propelled repulsive particles, for which a stable phase separation into a dilute and a dense phase is observed. We exploit the fact that for nonsquare boxes a stable "slab" configuration is reached, in which interfaces align with the shorter box edge. Evaluating a recent proposal for an intensive active swimming pressure, we demonstrate that the excess stress within the interface separating both phases is negative. The occurrence of a negative tension together with stable phase separation is a genuine nonequilibrium effect that is rationalized in terms of a positive stiffness, the estimate of which agrees excellently with the numerical data. Our results challenge effective thermodynamic descriptions and mappings of active Brownian particles onto passive pair potentials with attractions. PMID- 26371687 TI - Space-Bounded Church-Turing Thesis and Computational Tractability of Closed Systems. AB - We report a new limitation on the ability of physical systems to perform computation-one that is based on generalizing the notion of memory, or storage space, available to the system to perform the computation. Roughly, we define memory as the maximal amount of information that the evolving system can carry from one instant to the next. We show that memory is a limiting factor in computation even in lieu of any time limitations on the evolving system-such as when considering its equilibrium regime. We call this limitation the space bounded Church-Turing thesis (SBCT). The SBCT is supported by a simulation assertion (SA), which states that predicting the long-term behavior of bounded memory systems is computationally tractable. In particular, one corollary of SA is an explicit bound on the computational hardness of the long-term behavior of a discrete-time finite-dimensional dynamical system that is affected by noise. We prove such a bound explicitly. PMID- 26371688 TI - Synthesis of in-plane and stacked graphene/hexagonal boron nitride heterostructures by combining with ion beam sputtering deposition and chemical vapor deposition. AB - Graphene/hexagonal boron nitride (h-BN) heterostructures have attracted a great deal of attention in recent years due to their unique and complementary properties for use in a wide range of potential applications. However, it still remains a challenge to synthesize large-area high quality samples by a scalable growth method. In this work, we present the synthesis of both in-plane and stacked graphene/h-BN heterostructures on Cu foils by sequentially depositing h BN via ion beam sputtering deposition (IBSD) and graphene with chemical vapor deposition (CVD). Due to a significant difference in the growth rate of graphene on h-BN and Cu, the in-plane graphene/h-BN heterostructures were rapidly formed on h-BN domain/Cu substrates. The large-area vertically stacked graphene/h-BN heterostructures were obtained by using the continuous h-BN film as a substrate. Furthermore, the well-designed sub-bilayered h-BN substrates provide direct evidence that the monolayered h-BN on Cu exhibits higher catalytic activity than the bilayered h-BN on Cu. The growth method applied here may have great potential in the scalable preparation of large-area high-quality graphene/h-BN heterostructures. PMID- 26371689 TI - Microfluidics using a thiol-acrylate resin for fluorescence-based pathogen detection assays. AB - We demonstrate thiol-acrylate microfluidics prepared via soft lithography for single-step protein immobilization and fluorescence-based pathogen detection. Such microfluidics are formed via room temperature curing, and bonded without oxygen plasma. The background fluorescence of the resin was found to be similar to PDMS for several filter sets. We also show that thiol-acrylate devices are able to bond to gold-coated surfaces, which allows for integration with microfabricated sensors. PMID- 26371690 TI - Different Interaction Mechanisms of Eu(III) and (243)Am(III) with Carbon Nanotubes Studied by Batch, Spectroscopy Technique and Theoretical Calculation. AB - Herein the sorption of Eu(III) and (243)Am(III) on multiwalled carbon nanotubes (CNTs) are studied, and the results show that Eu(III) and (243)Am(III) could form strong inner-sphere surface complexes on CNT surfaces. However, the sorption of Eu(III) on CNTs is stronger than that of (243)Am(III) on CNTs, suggesting the difference in the interaction mechanisms or properties of Eu(III) and (243)Am(III) with CNTs, which is quite different from the results of Eu(III) and (243)Am(III) interaction on natural clay minerals and oxides. On the basis of the results of density functional theory calculations, the binding energies of Eu(III) on CNTs are much higher than those of (243)Am(III) on CNTs, indicating that Eu(III) could form stronger complexes with the oxygen-containing functional groups of CNTs than (243)Am(III), which is in good agreement with the experimental results of higher sorption capacity of CNTs for Eu(III). The oxygen containing functional groups contribute significantly to the uptake of Eu(III) and (243)Am(III), and the binding affinity increases in the order of =S-OH < =S COOH < =S-COO(-). This paper highlights the interaction mechanism of Eu(III) and (243)Am(III) with different oxygen-containing functional groups of CNTs, which plays an important role for the potential application of CNTs in the preconcentration, removal, and separation of trivalent lanthanides and actinides in environmental pollution cleanup. PMID- 26371691 TI - Intensity modulated radiotherapy with simultaneous integrated boost vs. conventional radiotherapy with sequential boost for breast cancer - A preliminary result. AB - PURPOSE: This study was aimed to assess the acute dermatological adverse effect from two distinct RT techniques for breast cancer patients. We compared intensity modulated radiotherapy with simultaneous integrated boost (IMRT-SIB) and conventional radiotherapy followed by sequential boost (CRT-SB). METHODS: The study population was composed of 126 consecutive female breast cancer patients treated with breast conserving surgery. Sixty-six patients received IMRT-SIB to 2 dose levels simultaneously. They received 50.4 Gy at 1.8 Gy per fraction to the whole breast and 60.2 Gy at 2.15 Gy per fraction to the tumor bed by integral boost. Sixty patients in the CRT-SB group received 50 Gy in 25 fractions to the whole breast followed by a boost irradiation to tumor bed in 5-7 fractions to a total dose of 60-64 Gy. Acute skin toxicities were documented in agreement with the Common Terminology Criteria for Adverse Events version 3 (CTCAE v.3.0). RESULTS: Ninety-eight patients had grade 1 radiation dermatitis while 14 patients had grade 2. Among those with grade 2, there were 3 patients in IMRT-SIB group (4.5%) while 11 in CRT-SB group (18.3%). (P = 0.048) There was no patient with higher than grade 2 toxicity. Three year local control was 99.2%, 3-year disease free survival was 97.5% and 3-year overall survival was 99.2%. CONCLUSIONS: A significant reduction in the severity of acute radiation dermatitis from IMRT-SIB comparing with CRT-SB is demonstrated. PMID- 26371692 TI - Tumor size and stage of breast cancer in Cote d'Ivoire and Republic of Congo - Results from population-based cancer registries. AB - PURPOSE: Breast cancer is now the leading female cancer in sub-Saharan Africa, but there is relatively little information on breast cancer characteristics from this region. We studied, on a population basis, the size and stage of female breast cancer at diagnosis in Cote d'Ivoire and Republic of Congo. METHODS: Data on tumor size and stage of breast cancer at diagnosis were collected by population-based cancer registries in Abidjan (the capital of Cote d'Ivoire; 141 cases) and Brazzaville (the capital of Republic of Congo; 139 cases) from a random group of female breast cancer cases that were diagnosed in 2008-2009 using the same protocol. RESULTS: The majority of breast cancers in both countries were advanced cancers. In Cote d'Ivoire, 68% of tumors were >=5 cm in diameter and 74% of cancers were stage III or IV at diagnosis; the corresponding proportions in Republic of Congo were 63% and 81%. CONCLUSION: These results underscore the importance of increased awareness about early detection of breast cancer, as well as expansion of the capacity to provide appropriate diagnosis, treatment, and palliative care in sub-Saharan Africa. PMID- 26371693 TI - Activated phosphoinositide 3-kinase delta syndrome in a patient with a former diagnosis of common variable immune deficiency, bronchiectasis, and lymphoproliferative disease. PMID- 26371694 TI - Oxidative stress in schoolchildren with allergic rhinitis: propensity score matching case-control study. AB - BACKGROUND: Oxidative stress is defined as an imbalance between the level of reactive oxygen species and antioxidant mechanisms. Compared with asthma, the role of oxidative stress in allergic rhinitis (AR) has received little attention. OBJECTIVE: To investigate the association between overall systemic oxidative stress and AR. METHODS: We used a propensity score matching case-control study and selected 90 children who had experienced AR in the previous year. This AR group was then matched with 90 healthy children who comprised the control group. Propensity score matching, a statistical matching technique that accounts for the conditional probability of receiving an exposure given a vector of measured covariates, is used to reduce selection bias and potential confounders in observational study. Serum total antioxidant status (TAS) and total oxidant status (TOS) levels were determined using a commercially available assay kit. Medical records and personal information were also reviewed. RESULTS: No statistically significant differences were found between patients with regard to age, sex, height, weight, educational level of parent, monthly household income, or distance of home from a main road. The mean TAS and TOS levels in the patient group were significantly higher than those of the control group (P = .03 and .048, respectively). The oxidative stress index, which is defined as the ratio of TOS to TAS, also increased in the AR group with statistical propensity (P = .08). In a multivariate logistic analysis, only TAS and TOS levels were significantly associated with increased risk of allergic rhinitis. CONCLUSION: Patients with AR have systemically elevated oxidative stress and systemically elevated TAS levels. PMID- 26371695 TI - Respiratory diseases and allergic sensitization in swine breeders: a population based cross-sectional study. AB - BACKGROUND: The daily occupation as a swine breeder involves exposure to several bacterial components and organic dusts and inhalation of a large amount of allergens. OBJECTIVE: To investigate the risk of respiratory diseases and atopy in swine breeders compared with the general population living in the same area. METHODS: A population-based cross-sectional study was conducted in an agricultural area of northern Italy that enrolled a random sample of resident male breeders and non-breeders. Demographic features, comorbidities, and presence of allergic respiratory disease were retrieved through interview. Prick tests for common allergens were performed. An evaluation of pollen and mold in air samples taken inside and outside some swine confinement buildings also was performed. RESULTS: One hundred one male breeders (78 native-born, mean age +/- SD 43.0 +/- 11.1 years) and 82 non-breeders (43.0 +/- 11.1 years) were enrolled. When restricting the analysis to native-born subjects, breeders vs non-breeders showed a lower prevalence of respiratory allergy (12.8% vs 31.1%, respectively, P = .002), asthma (6.4% vs 15.8%, P = .059), rhinitis (16.7% vs 51.2%, P < .001), persistent cough (5.1% vs 15.9%, P = .028), and sensitization to grass (7.7% vs 25.6%, P = .002). There was no difference in prick test positivity, polysensitization, nasal cytologic pattern, forced expiratory volume in 1 second, and the ratio of forced expiratory volume in 1 second to forced vital capacity between breeders and non-breeders. Air concentration of molds and pollens was lower inside than outside the swine buildings investigated, particularly when the pigs were inside vs outside the buildings. CONCLUSION: This study suggests that swine breeding does not increase, and might decrease, the risk of pollen sensitization and allergic disease. PMID- 26371696 TI - Developing new extension of GafChromic RTQA2 film to patient quality assurance field using a plan-based calibration method. AB - GafChromic RTQA2 film is a type of radiochromic film designed for light field and radiation field alignment. The aim of this study is to extend the application of RTQA2 film to the measurement of patient specific quality assurance (QA) fields as a 2D relative dosimeter.Pre-irradiated and post-irradiated RTQA2 films were scanned in reflection mode using a flatbed scanner. A plan-based calibration (PBC) method utilized the mapping information of the calculated dose image and film grayscale image to create a dose versus pixel value calibration model. This model was used to calibrate the film grayscale image to the film relative dose image. The dose agreement between calculated and film dose images were analyzed by gamma analysis. To evaluate the feasibility of this method, eight clinically approved RapidArc cases (one abdomen cancer and seven head-and-neck cancer patients) were tested using this method. Moreover, three MLC gap errors and two MLC transmission errors were introduced to eight Rapidarc cases respectively to test the robustness of this method.The PBC method could overcome the film lot and post-exposure time variations of RTQA2 film to get a good 2D relative dose calibration result. The mean gamma passing rate of eight patients was 97.90% +/- 1.7%, which showed good dose consistency between calculated and film dose images. In the error test, the PBC method could over-calibrate the film, which means some dose error in the film would be falsely corrected to keep the dose in film consistent with the dose in the calculated dose image. This would then lead to a false negative result in the gamma analysis. In these cases, the derivative curve of the dose calibration curve would be non-monotonic which would expose the dose abnormality.By using the PBC method, we extended the application of more economical RTQA2 film to patient specific QA. The robustness of the PBC method has been improved by analyzing the monotonicity of the derivative of the calibration curve. PMID- 26371697 TI - Persistent otolith dysfunction even after successful repositioning in benign paroxysmal positional vertigo. AB - To evaluate utricular and saccular function during the acute and resolved phases of BPPV, ocular and cervical vestibular evoked myogenic potentials (VEMPs) were studied in 112 patients with BPPV and 50 normal controls in a referral-based University Hospital. Ocular (oVEMPs) and cervical VEMPs (cVEMPs) were induced using air-conducted sound (1000Hz tone burst, 100dB normal hearing level) at the time of initial diagnosis and 2 months after successful repositioning in patients with BPPV, and the results were compared with those of the controls. Abnormalities of cVEMPs and oVEMPs in patients with BPPV were prevalent and significantly higher compare to the healthy control group (p<0.01 in each VEMP by chi-square test). In the patient group, difference between the proportions of abnormal responses of cVEMP and oVEMP was not significant in both affected (p=0.37, chi-squared test) and non-affected (p=1.00) ears. The abnormalities were more likely reduced or absent responses rather than delayed ones; reduced or absent responses are 17.6% in cVEMPs (p=0.04, chi-square) and 21.6% in oVEMPs (p<0.01). The non-affected ear in the BPPV group also showed significantly higher abnormalities of cVEMP and oVEMP when compared to the control group. The follow up VEMPs after repositioning maneuvers were not significantly different compared to the initial values from both stimulated affected and non-affected ears. Although most patients had unilateral BPPV, bilateral otolithic dysfunction was often shown by persistently reduced or absent cervical and ocular VEMPs, suggesting that BPPV may be caused by significant bilateral damage to the otolith organs. PMID- 26371698 TI - A global health delivery framework approach to epilepsy care in resource-limited settings. AB - The Global Health Delivery (GHD) framework (Farmer, Kim, and Porter, Lancet 2013;382:1060-69) allows for the analysis of health care delivery systems along four axes: a care delivery value chain that incorporates prevention, diagnosis, and treatment of a medical condition; shared delivery infrastructure that integrates care within existing healthcare delivery systems; alignment of care delivery with local context; and generation of economic growth and social development through the health care delivery system. Here, we apply the GHD framework to epilepsy care in rural regions of low- and middle-income countries (LMIC) where there are few or no neurologists. PMID- 26371699 TI - Systemic therapy for pulmonary carcinoids. AB - Between 25 and 33% of neuroendocrine tumours arise in the lung as low-grade typical pulmonary carcinoids (TPC), intermediate-grade atypical pulmonary carcinoids (APC), and high-grade large cell neuroendocrine or small cell carcinomas. The relatively uncommon incidence and prevalence of PCs are progressively increasing. However, data regarding systemic treatment for PCs are limited, controversial and based on old reports with few randomized or placebo controlled trials, small sample sizes, or including tumours with very different behaviours. Moreover, conclusions are generally extrapolated from the outcome of extra-pulmonary carcinoids, treatment arms are not well defined or mix different therapies, and the indolent nature of some PCs is not adequately considered in designing control arms. Here, we reviewed and discuss current recommendations regarding systemic treatments for PCs. PMID- 26371700 TI - Pemetrexed plus platinum versus pemetrexed alone in non-small cell lung cancer patients who have progressed after first-line EGFR TKIs. AB - OBJECTIVES: After failure of first-line epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) in patients with non-small cell lung cancer (NSCLC) harboring EGFR-activating mutation, platinum based combination chemotherapy is recommended. However, it is still unknown which chemotherapeutic regimens result in better outcomes. MATERIALS AND METHODS: A total of 63 patients who were treated with pemetrexed or pemetrexed/platinum chemotherapy after first line EGFR TKI therapy at Samsung Medical Center were included in our analysis. Baseline clinical characteristics, response rate, toxicities and survival outcomes were compared between the two groups. RESULTS: Among 63 patients, 29 were treated with pemetrexed (P) alone and 34 were treated with pemetrexed and platinum combination (PC) therapy. The median age, sex and smoking history was not different between the two groups. The overall response rate and disease control rate was 25.9%/44.4% for the P group and 43.5%/75.0% for the PC group (p = 0.154 in response rate, p = 0.017 in disease control rate). Grade 2 or 3 neutropenia was noted only for the PC group (0% vs. 18.8%, p = 0.049). For progression-free survival (PFS), patients treated with PC had more favorable outcomes than patients treated with P alone, although the difference was not statistically significant (5.2 vs. 2.7 months, PC vs. P; p=0.096). CONCLUSIONS: Based on this retrospective analysis, platinum combination with pemetrexed resulted in a better disease control rate and a tendency toward prolongation of progression-free survival in NSCLC patients who progressed after first-line EGFR TKIs. PMID- 26371701 TI - Within-year fidelity growth of SWPBIS during installation and initial implementation. AB - The purpose of this study was to document within-year fidelity growth during installation and initial implementation of School-Wide Positive Behavioral Interventions and Supports (SWPBIS). Participants included school teams from schools throughout the United States that were in years 1 to 4 of SWPBIS implementation and routinely evaluated their implementation fidelity. The fidelity outcome was assessed with the Team Implementation Checklist (TIC) and was completed multiple times per year by SWPBIS teams. Results from multilevel fidelity growth models documented within- and between-school variability and growth predictors. Years implementing, location, school type, and enrollment size were significant predictors of beginning-year fidelity scores (intercept), and years implementing and relative socioeconomic status were significant predictors of the average rate of fidelity change per month of school (slope). These results add to the growing field of implementation science, and practice recommendations are outlined. (PsycINFO Database Record PMID- 26371703 TI - Oxygen reduction and oxygen evolution in DMSO based electrolytes: the role of the electrocatalyst. AB - In the present paper the role of the electrode material in oxygen reduction in DMSO based electrolytes is elucidated using DEMS. We have found, employing platinum, gold, ruthenium rhodium, selenium decorated rhodium and boron doped diamond (BDD) as electrode materials, that the actual mechanism of oxygen reduction largely depends on the electrode material. At platinum, rhodium and selenium decorated rhodium the final reduction product, peroxide, is formed electrochemically. At gold and at low overpotentials oxygen is reduced to superoxide and peroxide is only formed by disproportionation of the latter. No oxygen reduction takes place at the diamond surface of the BDD-electrode, hence, showing unambiguously that oxygen reduction is an inner sphere reaction. Also, the rate of oxygen evolution varies with the electrode material, although the onset potential of oxygen evolution is not influenced. The amount of peroxide formed is limited to 1-2 monolayers. Contrary to intuition oxygen reduction and oxygen evolution from peroxide, therefore, are heterogeneous, electrocatalytic reactions. The finding of such an electrocatalytic effect is of great importance for the development and optimization of lithium-air batteries. Aside from the electrode material there are also effects of water as well as of the cation used in the electrolyte. This suggests an influence of the double layer at the interface between the electrode and the electrolyte on oxygen reduction in addition to the well-known higher stability of Na2O2 and K2O2. Electrospray ionization (ESI) results show that any effect of water in the Li(+) containing electrolyte is not due to an altered solvation of the cation. PMID- 26371702 TI - Effects of CPAP on energy expenditure in obese obstructive sleep apnoea patients: A pilot study. AB - We conducted a placebo-controlled crossover pilot study investigating the effects of 2 mo of active and sham continuous positive airway pressure (CPAP) on energy expenditure (EE) via whole-room indirect calorimetry in three obese obstructive sleep apnoea (OSA) patients. Total 24-h (active: 2970 +/- 254 kcal/d, sham: 2705 +/- 217 kcal/d; p = 0.015) and mean sleeping (active: 1.60 +/- 0.20 kcal/min; sham: 1.47 +/- 0.17 kcal/min; p = 0.038) EE were significantly increased after active vs. sham CPAP. Findings suggest that CPAP may correct a hypoxia-related adaptive decrease in thermogenesis. PMID- 26371704 TI - Measurement of membrane tension of free standing lipid bilayers via laser-induced surface deformation spectroscopy. AB - Non-invasive measurement of the membrane tension of free-standing black lipid membranes (BLMs), with sensitivity on the order of MUN m(-1), was achieved using laser-induced surface deformation (LISD) spectroscopy. A BLM was vertically formed via the folding method and aqueous phases with different refractive indices were added on each side in order to induce radiation pressure by a laser beam. The dynamic response of the deformed BLMs was measured under periodic intensity modulation and their tensions could be estimated. The dependence of membrane tension on the cholesterol concentration of BLMs composed of phosphatidylcholine and phosphatidylethanolamine was investigated, with the membrane tension increasing from 1.3 MUN m(-1) to 68.1 MUN m(-1) when the cholesterol concentration increased from zero to 33%. These tension values are much smaller than some of those previously reported, because this method does not suppress membrane fluctuation unlike other conventional methods. Our LISD system can be a promising tool for the measurement of membrane tension in BLMs. PMID- 26371705 TI - The prognosis of bodily distress syndrome: a cohort study in primary care. AB - OBJECTIVE: Bodily distress syndrome (BDS) is a newly proposed diagnosis for functional disorders. The diagnosis is based on empirical research, but little is known about the course of the disease. We aimed to study the prognosis in terms of diagnosis stability over time. METHOD: A longitudinal study of 1356 primary care patients with 2-year follow-up was conducted in the Central Denmark Region. Data were obtained from family physician registration forms, patient questionnaires (including a BDS checklist) and nationwide registries. Complete data were available for 1001 patients (73.8%). RESULTS: Overall, 146 persons [14.6%, 95% confidence interval (CI): 12.5-16.9] fulfilled the criteria for BDS at baseline and 142 persons (14.2%, CI: 12.1-16.5) at follow-up. Among study participants with BDS at baseline, 56.8% (CI: 48.4-65.0) also had BDS at follow up. Multiorgan BDS tended to be more persistent (81.8%, CI: 48.2-97.7) than single-organ BDS (54.8%, CI: 46.0-63.4). Patients with BDS had fewer socioeconomic resources, experienced more emotional distress, and used more opioids and medical services. CONCLUSIONS: BDS is a common clinical condition being prone to chronicity; one in seven primary care patients met the criteria for BDS, and more than half of these patients still suffered from BDS 2 years later. PMID- 26371706 TI - The pro-inflammatory and anti-inflammatory cytokine profile in peripheral blood of women with recurrent implantation failure. AB - Limited information is available on the balance state of pro- and anti inflammatory cytokines in patients with recurrent implantation failure (RIF). This study assessed the pro- and anti-inflammatory cytokines in plasma of 34 patients with RIF, compared with those of 25 women with a successful pregnancy in the first IVF/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) cycle. The IFN-gamma, IL-1beta, IL-6 and IL-4 concentrations were higher, whereas the TGF-beta1 concentration was lower in the RIF group compared with the control group. Furthermore, the ratios of pro-inflammatory and anti-inflammatory cytokines IFN-gamma/IL-4, IFN-gamma/IL-10, IFN-gamma/TGF-beta1, IL-6/IL-10, IL 6/TGF-beta1, IL-1beta/TGF-beta1 and TNF-alpha/TGF-beta1 were higher in the RIF group (all P < 0.01). The results suggested a shift toward a pro-inflammatory state in peripheral blood of the patients with RIF. PMID- 26371708 TI - Accidentally delayed oocyte pickup--a challenge to the current paradigm. PMID- 26371707 TI - Assisted reproduction in Indonesia: policy reform in an Islamic culture and developing nation. AB - This article considers how religious and economic factors shape assisted reproductive technology (ART) policy in Indonesia, the world's most populous Muslim country. Infertility clinic policies are grounded on both the views of the country's powerful Islamic coalition and those of the worldwide Islamic community. Indonesian government officials, physicians, and Islamic scholars have expressed concern over who can use ART and which procedures can be performed. Indonesia has also faced economic challenges related to ART, including inadequate health insurance coverage, inequitable access to ART, and maintenance of expensive ART infrastructure. The prohibitive price of infertility treatment and regional differences in the provision of health care prohibit most Indonesians from obtaining ART. In the absence of a shift in religious mores and a rapid reduction in poverty and inequality, Indonesia will need to adopt creative means to make ART both more available and less necessary as a solution to infertility. This paper suggests policy reforms to promote more affordable treatment methods and support preventative health programmes to reduce infertility rates. This country-specific analysis of the laws and customs surrounding ART in Indonesia reveals that strategies to reduce infertility must be tailored to a country's unique religious and economic climate. PMID- 26371709 TI - Investigation of the Annexin A5 M2 haplotype in 500 white European couples who have experienced recurrent spontaneous abortion. AB - Annexin A5 is a placental anti-coagulant protein that contains four nucleotide substitutions (M2 haplotype) in its promoter. This haplotype is a risk factor for recurrent spontaneous abortion (RSA). The influence of the M2 haplotype in the gestational timing of spontaneous abortions, paternal risk and relationships with known risk factors were investigated. European couples (n = 500) who had experienced three or more consecutive spontaneous abortions, and two fertile control groups, were selected for this study. The allele frequency of M2 was significantly higher among patients who had experienced early RSA than among controls (P = 0.002). No difference was found between controls and patients who had undergone late spontaneous abortions. No difference was found between patients who had experienced RSA who had a live birth or no live births, or between patients who were positive or negative for known risk factors. Male and female partners in each group had similar allele frequencies of M2. The M2 haplotype is a risk factor for early spontaneous abortions, before the 12th week of gestation, and confers about the same relative risk to carriers of both sexes. Having one or more M2 allele(s) in combination with other risk factors further increases the RSA risk. PMID- 26371710 TI - Intended parents' motivations and information and support needs when seeking extraterritorial compensated surrogacy. AB - Cross-border reproductive care (CBRC) is becoming increasingly common. Little is known about the motivations and information and support needs of people who cross borders to access surrogacy. This study aimed to explore: how those considering or undertaking extraterritorial surrogacy reach their decision; what other avenues they have considered and tried to have children; their sources of information and support; and perceptions of how others view their decision. Members of two Australian parenting support forums completed an anonymous online survey. Of the 249 respondents, 51% were gay men, 43% heterosexual women and 7% heterosexual men. Most heterosexual respondents had tried to conceive spontaneously and with assisted reproductive technology before considering surrogacy. Most respondents felt supported in their decision to try extraterritorial surrogacy by close family and friends. Surrogacy-related information was mostly sourced online and from other parents through surrogacy. Few sought information from a local general practitioner or IVF clinic and those who did reported IVF clinic staff were significantly (P < 0.001) more likely than other groups to communicate negative reactions to their decision to seek surrogacy. The apparent negative attitudes to cross-border surrogacy among health professionals warrants further research into health professionals' knowledge, beliefs and attitudes relating to surrogacy. PMID- 26371711 TI - Caesarean delivery: conflicting interests. AB - Within the maternal-fetal relationship, interests may sometimes diverge. In this paper, a pregnant woman's refusal to undergo a caesarean delivery, which was recommended both to save the life of the fetus and to minimize risks to her, is described. The legal aspects involved in the conflict between maternal autonomy and fetal well-being are analysed. The patient requested an abortion because of the poor condition of the fetus; however, according to Spanish legislation, the possibility of abortion was rejected as the pregnancy was in its 27th week. The woman still persisted in her refusal to accept a caesarian delivery. After the medical team sought guidance on the course to follow, the Duty Court authorized a caesarean delivery against the wishes of the patient. From a legal point of view, at stake were the freedom of the woman - expressed by the decision to reject a caesarean delivery - and the life of the unborn child. In clinical treatment, the interests of the fetus are generally aligned with those of the pregnant woman. When they are not, it is the pregnant woman's autonomy that should be respected, and coercion should form no part of treatment, contrary to the decision of this court. PMID- 26371712 TI - Luteal phase support post IVF: individualized early stop. AB - While the need for progesterone-based luteal phase support is well documented, the required treatment duration is not well established, and a practitioners' survey showed a wide range of empiric stopping points. It is suggested that an early stop can be based on assessing endogenous luteal activity on the day of pregnancy test. To examine this approach, data were retrospectively collected on 99 patients with positive pregnancy test and high serum concentrations of oestradiol and progesterone (>= 1000 pmol/l and >= 110 nmol/l, respectively), whose luteal support was stopped, and compared with those of 85 patients who did not meet the above criteria, and so luteal support was continued until gestational week 9. Both groups were comparable in terms of live birth and miscarriage rates. We conclude that in the face of strong endogenous luteal activity, exogenous support can be stopped on pregnancy test day, without affecting pregnancy outcome. Further research is needed to substantiate this finding. PMID- 26371713 TI - The future historian: Reflections on the archives of contemporary sciences. AB - Historians working on recent science work close to where the archives are created or become accessible. Based on this experience, the essay presents a reflection on the archives of contemporary life sciences. It addresses three questions: firstly, what is special about the archival situation of contemporary sciences? Secondly, which sources do contemporary historians use and what opportunities and challenges do they offer? And finally, what potential changes to the archives of contemporary sciences are we witnessing? The essay draws a distinction between, on the one side, the history of science when the actors are still alive-a situation that presents a particular set of issues in respect to the available sources-and, on the other side, questions relating specifically to the life sciences at the turn of the millennium--a period which will eventually not be considered as 'contemporary' any more. It reviews changes in scientific practice, historiographical trends and archival practices and considers the place of paper records, digital sources, material artefacts and oral sources in the archives of contemporary sciences. It argues that the commercialisation and privatisation of science may prove a bigger problem for the future historian than the shift to the digital medium. It concludes by welcoming the closer interactions between scientists, historians, curators and archivists prompted by recent developments. PMID- 26371715 TI - Estimating duration of central venous catheter at time of insertion: Clinician judgment and clinical predictors. AB - PURPOSE: The aim of this study was to investigate whether clinicians can estimate the length of time a central venous catheter (CVC) will remain in place and to identify variables that may predict CVC duration. MATERIALS AND METHODS: We conducted a prospective study of patients admitted to the intensive care unit over a 1-year period. Clinicians estimated the anticipated CVC duration at time of insertion. We collected demographics, medical history, type of intensive care unit, anatomical site of CVC placement, vital signs, laboratory values, Sequential Organ Failure Assessment score, mechanical ventilation, and use of vasopressors. Pearson correlation coefficient was used to assess the correlation between estimated and actual CVC time. We performed multivariable logistic regression to identify predictors of long duration (>5 days). RESULTS: We enrolled 200 patients; median age was 65 years (quartiles 52, 75); 91 (46%) were female; and mortality was 24%. Correlation between estimated and actual CVC time was low (r=0.26; r2=0.07; P<.001). Mechanical ventilation (odds ratio, 2.20; 95% confidence interval, 1.22-3.97; P=.009) at time of insertion and a medical history of cancer (odds ratio, 0.35; 95% confidence interval, 0.16-0.75; P=.007) were significantly associated with long duration. CONCLUSION: Our results suggest a low correlation between clinician prediction and actual CVC duration. We did not find any strong predictors of long CVC duration identifiable at the time of insertion. PMID- 26371714 TI - Intraoperative opioids use for laryngeal squamous cell carcinoma surgery and recurrence: a retrospective study. AB - STUDY OBJECTIVE: To assess whether the use of intraoperative opioids is associated with poor recurrence-free survival (RFS) and overall survival (OS) after lung cancer surgery. DESIGN: Retrospective study. SETTING: Academic hospital. SUBJECTS: Patients with laryngeal primary or recurrent laryngeal squamous cell carcinoma who had surgery. INTERVENTIONS: Intravenous opioids (remifentanil, fentanyl, sufentanil, and hydromorphone). MEASUREMENTS: Univariate and multicovariate Cox proportional hazards models were applied to assess the effects of covariates of interest on OS and RFS. MAIN RESULTS: A total of 195 patients were included. All received opioids intraoperatively. The multivariate analysis demonstrated that age (hazard ratio [HR], 1.03; P = .005), negative margin status (HR, 0.163; P = .001], postoperative chemotherapy (HR, 7.38; P < .001), and concurrent chemotherapy and radiation (HR, 3.11; P < .001) treatment and fentanyl equivalent use (HR, 1.001; P = .02) were all predictor factors for 3 and 5-year RFS. The same variables were predictor factors for OS (age: HR, 1.03 [P = .003]; negative margin status: HR, 0.14 [P = .001]; postoperative chemotherapy: HR, 4 [P < .0001]; and fentanyl equivalent use: HR, 1.001 [P = .02]). CONCLUSIONS: Our study demonstrates a very weak association between the use of intraoperative opioids and cancer recurrence after laryngeal squamous cell carcinoma surgery. PMID- 26371716 TI - Hydrogen-Bonded Networks in Hydride Water Clusters, F-(H2O)n and Cl-(H2O)n: Cubic Form of F-(H2O)7 and Cl-(H2O)7. AB - The anion-water bonds and hydrogen bonds between water molecules in X( )(H(2)O)(n) (X = F and Cl, n = 3-7) clusters are analyzed by evaluating the charge-transfer (CT) and dispersion terms for every pair of ions and molecules with the perturbation theory based on the locally projected molecular orbitals. In particular, the relative stabilities and the bond strengths in all 11 distinct cubic X(-)(H(2)O)(7) isomers are analyzed by classifying the ligand water (L) with the numbers of the donating (n) and accepting (m) OHs as LD(n)A(m). The number of LD(0)A(2) waters determines the relative stability. It is demonstrated that the strengths of the anion-ligand bonds are strongly influenced by two other hydrogen bonds of the water molecules adjacent to the ligand. When the model theory of Mulliken's charge-transfer interaction is applied to the anion-ligand and water-water hydrogen bonds, the dependence of the bond strengths on the chains of the hydrogen bonds is explained. PMID- 26371718 TI - Editorial commentary: This sodium current may be late, but it is important. PMID- 26371719 TI - Direct Access to Axially Substituted Subphthalocyanines from Trimethylsilyl Protected Nucleophiles. AB - A new synthetic one-step approach to perform the axial ligand exchange reaction in subphthalocyanines that employs trimethylsilyl-protected nucleophiles as starting materials is reported. Theoretical calculations indicate that the exchange reaction proceeds through a similar 4-centered sigma-bond metathesis transition state as the substitution with phenols. This direct method allowed us to synthesize new axial derivatives of singular importance within the chemistry of subphthalocyanines, for which the reactivity and X-ray crystalline structure were studied. PMID- 26371720 TI - Avoiding exposure to air pollution by using filtering facemask respirators: An application of the health action process approach. AB - OBJECTIVES: Adherence to the use of filtering facemask respirators on hazy days to reduce exposure to air pollution is examined with the aim of uncovering psychological mechanisms that may be responsible for individual differences in motivation and behavior. METHODS: In a longitudinal survey, 164 young adults from Beijing, China, completed assessments at baseline (Time 1), 2 weeks (Time 2), and 4 weeks later (Time 3). Self-efficacy, risk perception, and outcome expectancies were measured along with intention at Time 1, planning and action control at Time 2, and facemask use at Time 3. A structural equation model was specified to test theory-implied pathways of influence. RESULTS: Self-efficacy and risk perception jointly predicted behavioral intention at Time 1. Planning and action control at Time 2 jointly predicted behavior at Time 3, serving as parallel mediators between intention (Time 1) and facemask use (Time 3). The model explained 19.5% and 30.2% of the variance in intention and behavior, respectively. CONCLUSIONS: Results support theory-based psychological mechanisms, with a focus on planning and action control, which might be influential in the adoption and maintenance of self-protective facemask wearing. PMID- 26371721 TI - User's guide to mechanism of action and clinical use of GLP-1 receptor agonists. AB - Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) are injectable glucose-lowering medications approved for the treatment of adult patients with type 2 diabetes mellitus (T2DM). This article provides practical information to guide primary care physicians on the use of GLP-1RAs in patients with T2DM. Two short-acting (once- or twice-daily administration; exenatide and liraglutide) and three long-acting (weekly administration; albiglutide, dulaglutide and exenatide) GLP-1RAs are currently approved in the US. These drugs provide levels of GLP-1 receptor agonism many times that of endogenous GLP-1. The GLP-1RAs have been shown to significantly improve glycemic parameters and reduce body weight. These agents work by activating GLP-1 receptors in the pancreas, which leads to enhanced insulin release and reduced glucagon release-responses that are both glucose-dependent-with a consequent low risk for hypoglycemia. Effects on GLP-1 receptors in the CNS and the gastrointestinal tract cause reduced appetite and delayed glucose absorption due to slower gastric emptying. The most common adverse effects are gastrointestinal, which are transient and less common with the long-acting drugs. GLP-1RAs are recommended as second-line therapy in combination with metformin, sulfonylureas, thiazolidinediones or basal insulin, providing a means of enhancing glucose control while offsetting the weight gain associated with insulin and some oral agents. GLP-1RAs represent a useful tool that the primary care physician can use to help patients with T2DM achieve their therapeutic goals. PMID- 26371722 TI - Will personalized drugs for cardiovascular disease become an option? - Defining 'Evidence-based personalized medicine' for its implementation and future use. AB - It is generally accepted that the implementation of pharmacogenomics and, more broadly, personalized medicine will have to be 'evidence-based'. However, there is a lack of consensus on the level of evidence required to justify the use of pharmacogenomic testing in clinical practice. In the cardiovascular field, this lack of agreement has led to somewhat contradicting recommendations by different organizations regarding the clinical utility and use of pharmacogenomic tests or information. Here, we argue that randomized, controlled trials are paramount in order to enable and accelerate the widespread implementation of pharmacogenomics, not only to demonstrate the clinical efficacy and cost-effectiveness of such tests, but because such level of evidence is required to support the considerable changes associated with the implantation of pharmacogenomics in clinical practice. PMID- 26371723 TI - Radiation Dermatitis Often Misdiagnosed as Contact Dermatitis. PMID- 26371724 TI - Correction. PMID- 26371726 TI - Correction. PMID- 26371725 TI - Increasing Potassium Intake May Help Mitigate Cardiovascular Risk. PMID- 26371728 TI - Family Physicians Contribute Significantly to Emergency Care of Medicare Patients in Urban and Suburban Areas. PMID- 26371729 TI - HPV Vaccination: Overcoming Parental and Physician Impediments. PMID- 26371730 TI - Navigating the Changes in Pneumococcal Immunizations for Adults. PMID- 26371731 TI - Update on Routine Childhood and Adolescent Immunizations. AB - Recommendations for routine vaccinations in children and adolescents have changed multiple times in recent years, based on findings in clinical trials, licensure of new vaccines, and evidence of waning immunity. Despite the overwhelming success of vaccinations, vaccine delay and refusal are leading to pockets of vaccine-preventable diseases. Schedules for diphtheria and tetanus toxoids, and acellular pertussis (DTaP); hepatitis A and B; Haemophilus influenzae type b (Hib); inactivated poliovirus; varicella; and measles, mumps, and rubella are unchanged. However, since 2008, 13-valent pneumococcal conjugate vaccine has replaced the 7-valent vaccine; a new two-dose oral rotavirus vaccine has been approved; use of the tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine has been expanded to children seven to 10 years of age who received fewer than five doses of DTaP, as well as during each pregnancy; a booster dose of meningococcal vaccine is recommended in adolescents 16 to 18 years of age (unless the first dose was given after 16 years of age); new meningococcal vaccines have been approved for use in infants at high risk of meningococcal disease; influenza vaccine has been expanded to routine use in all children six months and older; and the human papillomavirus vaccine has been approved for routine immunization of adolescent boys and girls. For the 2015-2016 influenza season, either live attenuated or inactivated vaccine can be administered to healthy children two to eight years of age. PMID- 26371732 TI - Skin and Soft Tissue Infections. AB - Skin and soft tissue infections result from microbial invasion of the skin and its supporting structures. Management is determined by the severity and location of the infection and by patient comorbidities. Infections can be classified as simple (uncomplicated) or complicated (necrotizing or nonnecrotizing), or as suppurative or nonsuppurative. Most community-acquired infections are caused by methicillin-resistant Staphylococcus aureus and beta-hemolytic streptococcus. Simple infections are usually monomicrobial and present with localized clinical findings. In contrast, complicated infections can be mono- or polymicrobial and may present with systemic inflammatory response syndrome. The diagnosis is based on clinical evaluation. Laboratory testing may be required to confirm an uncertain diagnosis, evaluate for deep infections or sepsis, determine the need for inpatient care, and evaluate and treat comorbidities. Initial antimicrobial choice is empiric, and in simple infections should cover Staphylococcus and Streptococcus species. Patients with complicated infections, including suspected necrotizing fasciitis and gangrene, require empiric polymicrobial antibiotic coverage, inpatient treatment, and surgical consultation for debridement. Superficial and small abscesses respond well to drainage and seldom require antibiotics. Immunocompromised patients require early treatment and antimicrobial coverage for possible atypical organisms. PMID- 26371733 TI - Potassium Disorders: Hypokalemia and Hyperkalemia. AB - Hypokalemia and hyperkalemia are common electrolyte disorders caused by changes in potassium intake, altered excretion, or transcellular shifts. Diuretic use and gastrointestinal losses are common causes of hypokalemia, whereas kidney disease, hyperglycemia, and medication use are common causes of hyperkalemia. When severe, potassium disorders can lead to life-threatening cardiac conduction disturbances and neuromuscular dysfunction. Therefore, a first priority is determining the need for urgent treatment through a combination of history, physical examination, laboratory, and electrocardiography findings. Indications for urgent treatment include severe or symptomatic hypokalemia or hyperkalemia; abrupt changes in potassium levels; electrocardiography changes; or the presence of certain comorbid conditions. Hypokalemia is treated with oral or intravenous potassium. To prevent cardiac conduction disturbances, intravenous calcium is administered to patients with hyperkalemic electrocardiography changes. Insulin, usually with concomitant glucose, and albuterol are preferred to lower serum potassium levels in the acute setting; sodium polystyrene sulfonate is reserved for subacute treatment. For both disorders, it is important to consider potential causes of transcellular shifts because patients are at increased risk of rebound potassium disturbances. PMID- 26371734 TI - Management of Constipation in Older Adults. AB - Chronic constipation is common in adults older than 60 years, and symptoms occur in up to 50% of nursing home residents. Primary constipation is also referred to as functional constipation. Secondary constipation is associated with chronic disease processes, medication use, and psychosocial issues. Fecal impaction should be treated with mineral oil or warm water enemas. Most patients are initially treated with lifestyle modifications, such as scheduled toileting after meals, increased fluid intake, and increased dietary fiber intake. Additional fiber intake in the form of polycarbophil, methylcellulose, or psyllium may improve symptoms. Fiber intake should be slowly increased over several weeks to decrease adverse effects. The next step in the treatment of constipation is the use of an osmotic laxative, such as polyethylene glycol, followed by a stool softener, such as docusate sodium, and then stimulant laxatives. Long-term use of magnesium-based laxatives should be avoided because of potential toxicity. If symptoms do not improve, a trial of linaclotide or lubiprostone may be appropriate, or the patient may be referred for further diagnostic evaluation. Peripherally acting mu-opioid antagonists are effective for opioid-induced constipation but are expensive. PMID- 26371735 TI - Behavioral Counseling to Promote a Healthful Diet and Physical Activity for Cardiovascular Disease Prevention in Adults with Cardiovascular Risk Factors. PMID- 26371736 TI - Nausea and Vomiting in Early Pregnancy. PMID- 26371743 TI - Treating and Preventing Constipation. PMID- 26371738 TI - Rapidly Progressing Rash in an Adult. PMID- 26371744 TI - Potassium: What if I'm Getting Too Much or Not Enough? PMID- 26371745 TI - Skin and Soft Tissue Infections. PMID- 26371747 TI - Physical, Financial, and Psychological Abuse Committed Against Older Women by Relatives With Psychiatric Disorders: Extent of the Problem. AB - Persons with psychiatric disorders (PD) are known to be at an increased risk of committing elder abuse, with much of this abuse occurring toward women. However, there is no evidence available speaking to the extent of this problem. The objective of the present study is to explore rates of abuse committed against older women by a relative with PD. In conjunction with the University of Pennsylvania, 217 women residing across the United States who are at least 55 years of age and who have a relative with PD completed an online survey. Analyses found that in the past 6 months 15% of survey respondents experienced physical abuse committed by their relative with PD, 20% experienced financial abuse, and 42% experienced psychological abuse. Given these high rates of abuse it is imperative that research into factors predicting abuse be conducted, as such information would help target and determine the nature of interventions. PMID- 26371746 TI - Bendamustine reactivates latent Epstein-Barr virus. PMID- 26371748 TI - Revealing Surface Waters on an Antifreeze Protein by Fusion Protein Crystallography Combined with Molecular Dynamic Simulations. AB - Antifreeze proteins (AFPs) adsorb to ice through an extensive, flat, relatively hydrophobic surface. It has been suggested that this ice-binding site (IBS) organizes surface waters into an ice-like clathrate arrangement that matches and fuses to the quasi-liquid layer on the ice surface. On cooling, these waters join the ice lattice and freeze the AFP to its ligand. Evidence for the generality of this binding mechanism is limited because AFPs tend to crystallize with their IBS as a preferred protein-protein contact surface, which displaces some bound waters. Type III AFP is a 7 kDa globular protein with an IBS made up two adjacent surfaces. In the crystal structure of the most active isoform (QAE1), the part of the IBS that docks to the primary prism plane of ice is partially exposed to solvent and has clathrate waters present that match this plane of ice. The adjacent IBS, which matches the pyramidal plane of ice, is involved in protein protein crystal contacts with few surface waters. Here we have changed the protein-protein contacts in the ice-binding region by crystallizing a fusion of QAE1 to maltose-binding protein. In this 1.9 A structure, the IBS that fits the pyramidal plane of ice is exposed to solvent. By combining crystallography data with MD simulations, the surface waters on both sides of the IBS were revealed and match well with the target ice planes. The waters on the pyramidal plane IBS were loosely constrained, which might explain why other isoforms of type III AFP that lack the prism plane IBS are less active than QAE1. The AFP fusion crystallization method can potentially be used to force the exposure to solvent of the IBS on other AFPs to reveal the locations of key surface waters. PMID- 26371750 TI - Categorising intersectional targets: An "either/and" approach to race- and gender emotion congruity. AB - Research on the interaction of emotional expressions with social category cues in face processing has focused on whether specific emotions are associated with single-category identities, thus overlooking the influence of intersectional identities. Instead, we examined how quickly people categorise intersectional targets by their race, gender, or emotional expression. In Experiment 1, participants categorised Black and White faces displaying angry, happy, or neutral expressions by either race or gender. Emotion influenced responses to men versus women only when gender was made salient by the task. Similarly, emotion influenced responses to Black versus White targets only when participants categorised by race. In Experiment 2, participants categorised faces by emotion so that neither category was more salient. As predicted, responses to Black women differed from those to both Black men and White women. Thus, examining race and gender separately is insufficient to understanding how emotion and social category cues are processed. PMID- 26371749 TI - Imaging Cerebral Microhemorrhages in Military Service Members with Chronic Traumatic Brain Injury. AB - PURPOSE: To detect cerebral microhemorrhages in military service members with chronic traumatic brain injury by using susceptibility-weighted magnetic resonance (MR) imaging. The longitudinal evolution of microhemorrhages was monitored in a subset of patients by using quantitative susceptibility mapping. MATERIALS AND METHODS: The study was approved by the Walter Reed National Military Medical Center institutional review board and is compliant with HIPAA guidelines. All participants underwent two-dimensional conventional gradient recalled-echo MR imaging and three-dimensional flow-compensated multiecho gradient-recalled-echo MR imaging (processed to generate susceptibility-weighted images and quantitative susceptibility maps), and a subset of patients underwent follow-up imaging. Microhemorrhages were identified by two radiologists independently. Comparisons of microhemorrhage number, size, and magnetic susceptibility derived from quantitative susceptibility maps between baseline and follow-up imaging examinations were performed by using the paired t test. RESULTS: Among the 603 patients, cerebral microhemorrhages were identified in 43 patients, with six excluded for further analysis owing to artifacts. Seventy seven percent (451 of 585) of the microhemorrhages on susceptibility-weighted images had a more conspicuous appearance than on gradient-recalled-echo images. Thirteen of the 37 patients underwent follow-up imaging examinations. In these patients, a smaller number of microhemorrhages were identified at follow-up imaging compared with baseline on quantitative susceptibility maps (mean +/- standard deviation, 9.8 microhemorrhages +/- 12.8 vs 13.7 microhemorrhages +/- 16.6; P = .019). Quantitative susceptibility mapping-derived quantitative measures of microhemorrhages also decreased over time: -0.85 mm(3) per day +/- 1.59 for total volume (P = .039) and -0.10 parts per billion per day +/- 0.14 for mean magnetic susceptibility (P = .016). CONCLUSION: The number of microhemorrhages and quantitative susceptibility mapping-derived quantitative measures of microhemorrhages all decreased over time, suggesting that hemosiderin products undergo continued, subtle evolution in the chronic stage. PMID- 26371751 TI - Phenolic profiles and antioxidant capacities of crude extracts and subsequent fractions from Potentilla fruticosa L. leaves. AB - This work aimed to further investigate the phenolic profiles and antioxidant capacities of the crude extracts and the subsequent fractions of Potentilla fruticosa leaves. Result showed that P. fruticosa leaves contained high amounts for hyperoside, ellagic acid and (+)-catechin contents, and the highest amount being registered for hyperoside (17.67 mg g(-1)). Nine sub-fractions were obtained after column chromatographic separation. EF-3, EF-4, EF-5 and BF-2 presented higher values for their total phenolic or flavonoid, (+)-catechin, ellagic acid and hyperoside content. Besides, EF-3, EF-4, BF-2 and BF-3 showed significant in vitro antioxidant capacities and protective effects on Escherichia coli under peroxide stress. The correlation between chromatograms and antioxidant activity showed that (+)-catechin, ellagic acid and hyperoside may play crucial roles in the antioxidant capacities of P. fruticosa and could be used as chemical markers for its quality assessment. Moreover, this is the first time P. fruticosa leaves have been systematically studied. PMID- 26371753 TI - Physical examination-indicated cerclage in singleton and twin pregnancies: maternal-fetal outcomes. AB - OBJECTIVES: To study maternal and perinatal outcomes after physical examination indicated cerclage in both singleton and twin pregnancies and evaluate the possible risk factors associated. STUDY DESIGN: Retrospective review of all women undergoing physical examination-indicated cerclage at the Hospital Vall d'Hebro, Barcelona from January 2009 to December 2012 after being diagnosed with cervical incompetence and risk of premature birth. RESULTS: During the study period, 60 cases of women diagnosed with cervical incompetence who were carrying live and morphologically-normal fetuses (53 singleton and 7 twin pregnancies), and who had an imminent risk of premature birth were evaluated. Mean gestational age until birth was 35 weeks in singleton and 32 weeks in twin pregnancies. Four cases (7.5%) of immature births and one case (2.0%) of neonatal death were recorded in singleton pregnancies. No cases of immature births or neonatal deaths were recorded in twin pregnancies. Diagnostic amniocentesis was performed IN all cases to rule out possible chorioamnionitis. CONCLUSIONS: Physical examination indicated cerclage for cervical incompetence in women at risk for immature or preterm birth demonstrates good perinatal prognosis without increasing maternal morbidity in either singleton or twin pregnancies. The increase in gestation time in our study may also have been due to the fact that patients with subclinical chorioamnionitis were excluded by diagnostic amniocentesis. PMID- 26371754 TI - Fibroblast-Derived Extracellular Matrices: An Alternative Cell Culture System That Increases Metastatic Cellular Properties. AB - Poor survival rates from lung cancer can largely be attributed to metastatic cells that invade and spread throughout the body. The tumor microenvironment (TME) is composed of multiple cell types, as well as non-cellular components. The TME plays a critical role in the development of metastatic cancers by providing migratory cues and changing the properties of the tumor cells. The Extracellular Matrix (ECM), a main component of the TME, has been shown to change composition during tumor progression, contributing to cancer cell invasion and survival away from the primary cancer site. Although the ECM is well-known to influence the fate of tumor progression, little is known about the molecular mechanisms that are affected by the cancer cell-ECM interactions. It is imperative that these mechanisms are elucidated in order to properly understand and prevent lung cancer dissemination. However, common in vitro studies do not incorporate these interactions into everyday cell culture assays. We have adopted a model that examines decellularized human fibroblast-derived ECM as a 3-dimensional substrate for growth of lung adenocarcinoma cell lines. Here, we have characterized the effect of fibroblast-derived matrices on the properties of various lung-derived epithelial cell lines, including cancerous and non-transformed cells. This work highlights the significance of the cell-ECM interaction and its requirement for incorporation into in vitro experiments. Implementation of a fibroblast-derived ECM as an in vitro technique will provide researchers with an important factor to manipulate to better recreate and study the TME. PMID- 26371755 TI - Rheumatic Heart Disease-Attributable Mortality at Ages 5-69 Years in Fiji: A Five Year, National, Population-Based Record-Linkage Cohort Study. AB - BACKGROUND: Rheumatic heart disease (RHD) is considered a major public health problem in developing countries, although scarce data are available to substantiate this. Here we quantify mortality from RHD in Fiji during 2008-2012 in people aged 5-69 years. METHODS AND FINDINGS: Using 1,773,999 records derived from multiple sources of routine clinical and administrative data, we used probabilistic record-linkage to define a cohort of 2,619 persons diagnosed with RHD, observed for all-cause mortality over 11,538 person-years. Using relative survival methods, we estimated there were 378 RHD-attributable deaths, almost half of which occurred before age 40 years. Using census data as the denominator, we calculated there were 9.9 deaths (95% CI 9.8-10.0) and 331 years of life-lost (YLL, 95% CI 330.4-331.5) due to RHD per 100,000 person-years, standardised to the portion of the WHO World Standard Population aged 0-69 years. Valuing life using Fiji's per-capita gross domestic product, we estimated these deaths cost United States Dollar $6,077,431 annually. Compared to vital registration data for 2011-2012, we calculated there were 1.6-times more RHD-attributable deaths than the number reported, and found our estimate of RHD mortality exceeded all but the five leading reported causes of premature death, based on collapsed underlying cause-of-death diagnoses. CONCLUSIONS: Rheumatic heart disease is a leading cause of premature death as well as an important economic burden in this setting. Age standardised death rates are more than twice those reported in current global estimates. Linkage of routine data provides an efficient tool to better define the epidemiology of neglected diseases. PMID- 26371756 TI - Evolution of the Role of RA and FGF Signals in the Control of Somitogenesis in Chordates. AB - During vertebrate development, the paraxial mesoderm becomes segmented, forming somites that will give rise to dermis, axial skeleton and skeletal muscles. Although recently challenged, the "clock and wavefront" model for somitogenesis explains how interactions between several cell-cell communication pathways, including the FGF, RA, Wnt and Notch signals, control the formation of these bilateral symmetric blocks. In the cephalochordate amphioxus, which belongs to the chordate phylum together with tunicates and vertebrates, the dorsal paraxial mesendoderm also periodically forms somites, although this process is asymmetric and extends along the whole body. It has been previously shown that the formation of the most anterior somites in amphioxus is dependent upon FGF signalling. However, the signals controlling somitogenesis during posterior elongation in amphioxus are still unknown. Here we show that, contrary to vertebrates, RA and FGF signals act independently during posterior elongation and that they are not mandatory for posterior somites to form. Moreover, we show that RA is not able to buffer the left/right asymmetry machinery that is controlled through the asymmetric expression of Nodal pathway actors. Our results give new insights into the evolution of the somitogenesis process in chordates. They suggest that RA and FGF pathways have acquired specific functions in the control of somitogenesis in vertebrates. We propose that the "clock and wavefront" system was selected specifically in vertebrates in parallel to the development of more complex somite derived structures but that it was not required for somitogenesis in the ancestor of chordates. PMID- 26371757 TI - The Role of the Immune Response in the Pathogenesis of Thyroid Eye Disease: A Reassessment. AB - BACKGROUND: Although thyroid eye disease is a common complication of Graves' disease, the pathogenesis of the orbital disease is poorly understood. Most authorities implicate the immune response as an important causal factor. We sought to clarify pathogenesis by using gene expression microarray. METHODS: An international consortium of ocular pathologists and orbital surgeons contributed formalin fixed orbital biopsies. RNA was extracted from orbital tissue from 20 healthy controls, 25 patients with thyroid eye disease (TED), 25 patients with nonspecific orbital inflammation (NSOI), 7 patients with sarcoidosis and 6 patients with granulomatosis with polyangiitis (GPA). Tissue was divided into a discovery set and a validation set. Gene expression was quantified using Affymetrix U133 Plus 2.0 microarrays which include 54,000 probe sets. RESULTS: Principal component analysis showed that gene expression from tissue from patients with TED more closely resembled gene expression from healthy control tissue in comparison to gene expression characteristic of sarcoidosis, NSOI, or granulomatosis with polyangiitis. Unsupervised cluster dendrograms further indicated the similarity between TED and healthy controls. Heat maps based on gene expression for cytokines, chemokines, or their receptors showed that these inflammatory markers were associated with NSOI, sarcoidosis, or GPA much more frequently than with TED. CONCLUSION: This is the first study to compare gene expression in TED to gene expression associated with other causes of exophthalmos. The juxtaposition shows that inflammatory markers are far less characteristic of TED relative to other orbital inflammatory diseases. PMID- 26371758 TI - Infection by Intestinal Parasites, Stunting and Anemia in School-Aged Children from Southern Angola. AB - INTRODUCTION: Intestinal parasites are responsible for morbidity in children worldwide, especially in low income countries. In the present study we determine the prevalence of intestinal parasites and explore its association with anemia and stunting in school-aged children. METHODS: A cross-sectional study was conducted from September to October 2010 enrolling 328 children attending the primary school in Lubango, the second largest city after the capital Luanda. Stool samples were collected for parasite detection through microscopy and molecular identification of Entamoeba histolytica and Entamoeba dispar. Stunting was assessed using the z-scores of height for age and hemoglobin concentration was determined using a portable hemoglobin analyzing system. RESULTS: The global prevalence of pathogenic intestinal parasites was 44.2%, the most common being Ascaris lumbricoides (22.0%), Giardia lamblia (20.1%) and Hymenolepis nana (8.8%). Molecular detection revealed that 13.1% of the children carried E. dispar and 0.3% were infected with E. histolytica. The prevalence of stunting (mild to severe) was 41.5%. Stunting was more frequent in older children (p = 0.006, OR = 1.886), while anemia was more frequent in younger children (p = 0.005, OR = 2.210). The prevalence of anemia was 21.6%, and we found a significant association with infection by H. nana (p = 0.031, OR = 2.449). CONCLUSIONS: This is one of the few published studies reporting intestinal parasites infection, nutritional status and anemia in children from Angola. Furthermore, the present work highlights the importance of regular intestinal parasites screening in children. PMID- 26371759 TI - Lichen Secondary Metabolite, Physciosporin, Inhibits Lung Cancer Cell Motility. AB - Lichens produce various unique chemicals that can be used for pharmaceutical purposes. To screen for novel lichen secondary metabolites showing inhibitory activity against lung cancer cell motility, we tested acetone extracts of 13 lichen samples collected in Chile. Physciosporin, isolated from Pseudocyphellaria coriacea (Hook f. & Taylor) D.J. Galloway & P. James, was identified as an effective compound and showed significant inhibitory activity in migration and invasion assays against human lung cancer cells. Physciosporin treatment reduced both protein and mRNA levels of N-cadherin with concomitant decreases in the levels of epithelial-mesenchymal transition markers such as snail and twist. Physciosporin also suppressed KITENIN (KAI1 C-terminal interacting tetraspanin) mediated AP-1 activity in both the absence and presence of epidermal growth factor stimulation. Quantitative real-time PCR analysis showed that the expression of the metastasis suppressor gene, KAI1, was increased while that of the metastasis enhancer gene, KITENIN, was dramatically decreased by physciosporin. Particularly, the activity of 3'-untranslated region of KITENIN was decreased by physciosporin. Moreover, Cdc42 and Rac1 activities were decreased by physciosporin. These results demonstrated that the lichen secondary metabolite, physciosporin, inhibits lung cancer cell motility through novel mechanisms of action. PMID- 26371760 TI - Enhanced Tuberculosis Infection Treatment Outcomes after Implementation of QuantiFERON(r)-Gold Testing. AB - BACKGROUND: Use of the tuberculin skin test (TST) for diagnosis of latent tuberculosis infection (LTBI) among individuals who received the Bacille Calmette Guerin (BCG) vaccine is complicated by its potential cross-reaction with TST antigens which may cause false-positive results and lead to patient and physician reluctance to initiate LTBI treatment. QuantiFERON(r)-TB Gold (QFT-G) lacks this cross-reaction. We sought to study the impact of implementing QFT-G testing in 2006 on LTBI treatment initiation and completion at NYC chest clinics. METHODS: QFT-G results from 10/2006-12/2008 in NYC Department of Health and Mental Hygiene chest clinics were obtained from the electronic medical record system. The proportions of patients who initiated and completed treatment among patients tested with QFT-G were compared to those tested with TST from 10/2004-9/2006. RESULTS: Among 36,167 patients tested with QFT-G, 2,300 (6%) tested positive, 33,327 (93%) tested negative, and 540 (1%) had an indeterminate result. Among those who had a positive QFT-G test and deemed eligible, 985 (80%) initiated LTBI treatment and 490 (40%) completed treatment. Historically, among patients tested with TST, 7,073 (19%) tested positive (p<0.0001 compared to QFT-G); 3,182 (79%) of those eligible initiated LTBI treatment and 1,210 (30%) completed treatment (p<0.0001 compared to QFT-G). CONCLUSIONS: QFT-G implementation increased the proportion of patients completing LTBI treatment. Additional studies are needed in more settings to determine whether using QFT-G leads to a sustained increase in treatment completion. PMID- 26371762 TI - 3,4-Methylenedioxymethamphetamine facilitates fear extinction learning. AB - Acutely administered 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') has been proposed to have long-term positive effects on post-traumatic stress disorder (PTSD) symptoms when combined with psychotherapy. No preclinical data support a mechanistic basis for these claims. Given the persistent nature of psychotherapeutic gains facilitated by MDMA, we hypothesized that MDMA improves fear extinction learning, a key process in exposure-based therapies for PTSD. In these experiments, mice were first exposed to cued fear conditioning and treated with drug vehicle or MDMA before extinction training 2 days later. MDMA was administered systemically and also directly targeted to brain structures known to contribute to extinction. In addition to behavioral measures of extinction, changes in mRNA levels of brain-derived neurotrophic factor (Bdnf) and Fos were measured after MDMA treatment and extinction. MDMA (7.8 mg kg(-1)) persistently and robustly enhanced long-term extinction when administered before extinction training. MDMA increased the expression of Fos in the amygdala and medial prefrontal cortex (mPFC), whereas increases in Bdnf expression were observed only in the amygdala after extinction training. Extinction enhancements were recapitulated when MDMA (1 MUg) was infused directly into the basolateral complex of the amygdala (BLA), and enhancement was abolished when BDNF signaling was inhibited before extinction. These findings suggest that MDMA enhances fear memory extinction through a BDNF-dependent mechanism, and that MDMA may be a useful adjunct to exposure-based therapies for PTSD and other anxiety disorders characterized by altered fear learning. PMID- 26371761 TI - The Borrelia burgdorferi RelA/SpoT Homolog and Stringent Response Regulate Survival in the Tick Vector and Global Gene Expression during Starvation. AB - As the Lyme disease bacterium Borrelia burgdorferi traverses its enzootic cycle, alternating between a tick vector and a vertebrate host, the spirochete must adapt and persist in the tick midgut under prolonged nutrient stress between blood meals. In this study, we examined the role of the stringent response in tick persistence and in regulation of gene expression during nutrient limitation. Nutritionally starving B. burgdorferi in vitro increased the levels of guanosine tetraphosphate (ppGpp) and guanosine pentaphosphate (pppGpp), collectively referred to as (p)ppGpp, products of the bifunctional synthetase/hydrolase RelBbu (RelA/SpoT homolog). Conversely, returning B. burgdorferi to a nutrient-rich medium decreased (p)ppGpp levels. B. burgdorferi survival in ticks between the larval and nymph blood meals, and during starvation in vitro, was dependent on RelBbu. Furthermore, normal morphological conversion from a flat-wave shape to a condensed round body (RB) form during starvation was dependent on RelBbu; relBbu mutants more frequently formed RBs, but their membranes were compromised. By differential RNA sequencing analyses, we found that RelBbu regulates an extensive transcriptome, both dependent and independent of nutrient stress. The RelBbu regulon includes the glp operon, which is important for glycerol utilization and persistence in the tick, virulence factors and the late phage operon of the 32-kb circular plasmid (cp32) family. In summary, our data suggest that RelBbu globally modulates transcription in response to nutrient stress by increasing (p)ppGpp levels to facilitate B. burgdorferi persistence in the tick. PMID- 26371763 TI - Delayed emergence of behavioral and electrophysiological effects following juvenile ketamine exposure in mice. AB - Frequent ketamine abuse in adulthood correlates with increased risk of psychosis, as well as cognitive deficits, including disruption of higher-order executive function and memory formation. Although the primary abusers of ketamine are adolescents and young adults, few studies have evaluated its effects on juvenile cognition. Therefore, the current study analyzes the effect of adolescent ketamine exposure on cognitive development. Juvenile mice (4 weeks of age) were exposed to chronic ketamine (20 mg kg(-1), i.p. daily) for 14 days. Mice were tested immediately after exposure in the juvenile period (7 weeks of age) and again as adults (12 weeks of age). Measures included electroencephalography (EEG) in response to auditory stimulation, the social choice test, and a 6-arm radial water maze task. Outcome measures include low-frequency EEG responses, event related potential (ERP) amplitudes, indices of social behavior and indices of spatial working memory. Juvenile exposure to ketamine was associated with electrophysiological abnormalities in adulthood, particularly in induced theta power and the P80 ERP. The social choice test revealed that ketamine-exposed mice failed to exhibit the same age-related decrease in social interaction time as controls. Ketamine-exposed mice outperformed control mice as juveniles on the radial water maze task, but did not show the same age-related improvement as adult controls. These data support the hypothesis that juvenile exposure to ketamine produces long-lasting changes in brain function that are characterized by a failure to progress along normal developmental trajectories. PMID- 26371764 TI - Variable telomere length across post-mortem human brain regions and specific reduction in the hippocampus of major depressive disorder. AB - Stress can be a predisposing factor to psychiatric disorders and has been associated with decreased neurogenesis and reduced hippocampal volume especially in depression. Similarly, in white blood cells chronic psychological stress has been associated with telomere shortening and with mood disorders and schizophrenia (SZ). However, in previous post-mortem brain studies from occipital cortex and cerebellum, no difference in telomere length was observed in depression. We hypothesized that in psychiatric disorders, stress-driven accelerated cellular aging can be observed in brain regions particularly sensitive to stress. Telomere length was measured by quantitative-PCR in five brain regions (dorsolateral prefrontal cortex, hippocampus (HIPP), amygdala, nucleus accumbens and substantia nigra (SN)) in major depressive disorder (MDD), bipolar disorder, SZ and normal control subjects (N = 40, 10 subjects per group). We observed significant differences in telomere length across brain regions suggesting variable levels of cell aging, with SN and HIPP having the longest telomeres and the dorsolateral prefrontal cortex the shortest. A significant decrease (P < 0.02) in telomere length was observed specifically in the HIPP of MDD subjects even after controlling for age. In the HIPP of MDD subjects, several genes involved in neuroprotection and in stress response (FKBP5, CRH) showed altered levels of mRNA. Our results suggest the presence of hippocampal stress mediated accelerated cellular aging in depression. Further studies are needed to investigate the cellular specificity of these findings. PMID- 26371766 TI - Pulsed dye laser versus long pulsed Nd:YAG laser in the treatment of angiokeratoma of Fordyce: A randomized, comparative, observer-blinded study. AB - BACKGROUND: Angiokeratoma of Fordyce is typically asymptomatic, blue-to-red papules with a scaly surface located on the scrotum, shaft of penis or labia majora. They can be treated with some locally destructive treatment modalities such as excision, electrocoagulation, cryotherapy and laser. OBJECTIVES: To compare the effects of the pulsed dye laser versus long pulsed Nd:YAG laser in the treatment of angiokeratoma of Fordyce. METHODS: Twenty tow patients with angiokeratoma of Fordyce were included in this study. All participants received three sessions of pulsed dye laser on the selected side or part of lesional area and long pulsed Nd:YAG laser on the other side or part of lesional area. Two dermatologists independently evaluated the photographs of the baseline and two month follow-up after last session using a grade system in which treatment response was categorized into six grades. RESULTS: Both PDL and long pulsed Nd:YAG laser revealed statistically significant improvements in angiokeratoma of fordyce. Comparatively, there was a statistical difference between them (overall mean improvement with PDL, 61.8%, versus Nd:YAG, 77.63%; p < 0.005). CONCLUSIONS: Both PDL and 1064-nm Nd:YAG laser are effective and safe in the treatment of angiokeratoma of Fordyce with better response in Nd:YAG laser than pulsed dye laser. PMID- 26371765 TI - Abnormal context-reward associations in an immune-mediated neurodevelopmental mouse model with relevance to schizophrenia. AB - Impairments in central reward processing constitute an important aspect of the negative symptoms of schizophrenia. Despite its clinical relevance, the etiology of deficient reward processing in schizophrenia remains largely unknown. Here, we used an epidemiologically informed mouse model of schizophrenia to explore the effects of prenatal immune activation on reward-related functions. The model is based on maternal administration of the viral mimic PolyI:C and has been developed in relation to the epidemiological evidence demonstrating enhanced risk of schizophrenia and related disorders following prenatal maternal infection. We show that prenatal immune activation induces selective deficits in the expression (but not acquisition) of conditioned place preference for a natural reward (sucrose) without changing hedonic or neophobic responses to the reward. On the other hand, prenatal immune activation led to enhanced place preference for the psychostimulant drug cocaine, while it attenuated the locomotor reaction to the drug. The prenatal exposure did not alter negative reinforcement learning as assessed using a contextual fear conditioning paradigm. Our findings suggest that the nature of reward-related abnormalities following prenatal immune challenge depends on the specificity of the reward (natural reward vs drug of abuse) as well as on the valence domain (positive vs negative reinforcement learning). Moreover, our data indicate that reward abnormalities emerging in prenatally immune-challenged offspring may, at least in part, stem from an inability to retrieve previously established context-reward associations and to integrate such information for appropriate goal-directed behavior. PMID- 26371768 TI - Early Tumor-Infiltrating Dendritic Cells Change their Characteristics Drastically in Association with Murine Melanoma Progression. AB - Dendritic cells (DCs) have a critical effect on the outcome of adaptive immune responses against growing tumors. Tumor-infiltrating dendritic cells (TIDCs) play diverse roles in the regulation of tumor regression or growth, but the characteristics that distinguish those effects are obscure. In this study, we investigated the frequency, phenotype and function of TIDCs over time from early stages of melanoma growth in mice. Flow cytometric analysis revealed that the tumors were infiltrated by a significant population of CD11c+MHCII+ DCs, especially at an early stage of tumor growth. The allogeneic stimulatory capacity of TIDCs increased with tumor growth, while this capacity of DCs in lymph nodes decreased. TIDCs harvested at an early stage of melanoma (early TIDCs) accelerated tumor growth, but those harvested at a late stage (late TIDCs) delayed tumor progression when they were co-injected with melanoma cells. Furthermore, co-injection of early TIDCs failed to induce full immunocompetent maturation of CD8+ T cells, with much lower expression of IFNgamma, granzyme B and perforin within the tumor microenvironment. In conclusion, TIDCs change their characteristics from an immunoinhibitory to an immunostimulatory phenotype over time in association with tumor progression.Journal of Investigative Dermatology accepted article preview online, 15 September 2015. doi:10.1038/jid.2015.359. PMID- 26371767 TI - Pre-Analytical Determination of the Effect of Extended Warm or Cold Ischaemia on RNA Stability in the Human Ileum Mucosa. AB - The use of banked human tissue, obtained with informed consent after elective surgical procedures, represents a powerful model for understanding underlying mechanisms of diseases or therapeutic interventions and for establishing prognostic markers. However, donated tissues typically have varying times of warm ischaemia in situ due to blood arrest or cold ischaemia due to procurement and transportation. Hence, before using these tissues, it is important to carry out pre-analytical studies to ensure that they are representative of the in vivo state. In particular, tissues of the gastrointestinal tract have been thought to have low RNA stability. Therefore, this study aimed to determine if extended warm or cold ischaemia times and snap-freezing or banking in RNA stabilization solution affects RNA integrity or gene expression in human ileum mucosa. In short, ileum mucosa was collected for up to 1.5 h and 6 h of simulated warm or cold ischaemia respectively. Subsequently, RNA integrity and gene expressions were determined. It was found that RNA integrity remained high over the course of warm and cold ischaemia examined and there were in general no significant differences between snap-freezing and banking in RNA stabilization solution. Following the same trend, there were in general no significant changes in gene expressions measured (MYC, HIF1alpha, CDX, HMOX1 and IL1beta). In conclusion, RNA in the ileum mucosa is maintained at a high integrity and has stable gene expression over the examined time course of warm or cold ischaemia when banked in RNA stabilization solution or snap-frozen in liquid nitrogen. As the average warm and cold ischaemia times imposed by surgery and the process of tissue banking are shorter than the time period examined in this study, human ileum mucosa samples collected after surgeries could be used for gene expression studies. PMID- 26371769 TI - Development of a Model for Chemotherapy-Induced Alopecia: Profiling of Histological Changes in Human Hair Follicles After Chemotherapy. AB - Optimized research models are required to further understand the pathogenesis and prophylaxis of chemotherapy-induced alopecia (CIA). Our aim was to develop a mouse model for CIA by follicular unit transplantation of human hair follicles onto immunodeficient mice. Twenty-two weeks after transplantation, a single dose of cyclophosphamide (Cph) was administered to mice in the Cph100 (100 mg/kg) and Cph150 (150 mg/kg) groups. On day 6, hair follicles showed dystrophic changes with swollen dermal papilla and ectopic melanin clumping in the hair bulb. In addition, up-regulated expression of apoptotic regulators (P53, Fas/Fas-ligand, TRAIL/TRAIL receptor, and Bax), increased apoptotic matrix keratinocytes, down regulated Ki67 expression, and decreased melanogenic protein in the hair bulb were noted in both groups. After 12 treatment days, hair follicles in Cph100 mice appeared to diminish dystrophic changes. In contrast, hair follicles of Cph150 mice prematurely entered a dystrophic catagen phase after 9 treatment days, and immunofluorescence staining for Ki67 and melanogenic protein expressions was barely visible. Two hair follicle damage response pathways were observed in this model, namely dystrophic anagen (Cph100) and catagen (Cph150) pathways. Our model might be useful for further understanding the impact of chemotherapy on human hair follicles.Journal of Investigative Dermatology accepted article preview online, 15 September 2015. doi:10.1038/jid.2015.358. PMID- 26371770 TI - Expression of Sezary Biomarkers in the Blood of Erythrodermic Mycosis Fungoides Patients. PMID- 26371771 TI - Feasibility Study: Colombian Caribbean Folk Dances to Increase Physical Fitness and Health-Related Quality of Life in Older Women. AB - The objectives of the study were to describe the feasibility of an intervention in older women based on folk dances of the Colombian Caribbean region, and to analyze the effects of the intervention on physical fitness and health-related quality of life (HRQoL). A pilot study was conducted in a sample of 27 participants, 15 in the intervention group (IG) and 12 in the comparison group (CG). Caribbean Colombian dance rhythms were introduced as an intervention that lasted 12 weeks. Recruitment and retention was not optimal. Treatment fidelity components indicated that intervention was administered as intended. IG participants showed positive and statistically significant changes in some components of physical fitness. No significant changes were observed in HRQoL indicators for either group. In conclusion, the intervention was feasible, but recruitment and retention was challenging. Folk dances of the Colombian Caribbean region provoked significant results in physical fitness but not in HRQoL. PMID- 26371772 TI - Iron Carbide Nanoparticles Encapsulated in Mesoporous Fe-N-Doped Graphene-Like Carbon Hybrids as Efficient Bifunctional Oxygen Electrocatalysts. AB - It is highly crucial and challenging to develop bifunctional oxygen electrocatalysts for oxygen reduction reactions (ORRs) and oxygen evolution reactions (OERs) in rechargeable metal-air batteries and unitized regenerative fuel cells (URFCs). Herein, a facile and cost-effective strategy is developed to prepare mesoporous Fe-N-doped graphene-like carbon architectures with uniform Fe3C nanoparticles encapsulated in graphitic layers (Fe3C@NG) via a one-step solid-state thermal reaction. The optimized Fe3C@NG800-0.2 catalyst shows comparable ORR activity with the state-of-the-art Pt/C catalyst and OER activity with the benchmarking RuO2 catalyst. The oxygen electrode activity parameter DeltaE (the criteria for judging the overall catalytic activity of bifunctional electrocatalysts) value for Fe3C@NG800-0.2 is 0.780 V, which surpasses those of Pt/C and RuO2 catalysts as well as those of most nonprecious metal catalysts. Significantly, excellent long-term catalytic durability holds great promise in fields of rechargeable metal-air batteries and URFCs. PMID- 26371773 TI - Predictive factors for perioperative blood transfusion in neck dissection. AB - OBJECTIVES/HYPOTHESIS: There is growing interest in reducing the exposure of patients to allogeneic blood transfusions by lowering preoperative cross-matched blood ordering and adopting alternative practices, such as autologous blood donations. Our aim was to investigate the predictors for perioperative blood transfusion (PBT) in head and neck cancer patients undergoing neck dissection (ND). STUDY DESIGN: Retrospective cohort study. METHODS: Retrospective observational study. All patients who underwent ND between January 2011 and August 2014. The primary outcome measure was PBT. Predictors tested included: gender, age, American Society of Anesthesiologists comorbidity score, Charlson comorbidity index, preoperative hemoglobin level, head and neck primary tumor location, tumor and nodal staging, side and laterality of ND, central versus lateral ND, elective ND, preoperative chemotherapy/radiotherapy/I(131) therapy, history of previous ND, other surgical procedures in addition to the ND, bone resection, use and type of reconstruction, and the use of bony free flap reconstruction. RESULTS: Twenty-one preoperative and operative variables were tested for an association with PBT using univariate and multivariate analyses. Multivariate analysis found only the following three predictors to be significantly associated with PBT in patients undergoing ND: low preoperative hemoglobin level, advanced N stage, and concurrent reconstructive surgery. CONCLUSION: Evaluation of specific risk factors for predicting the need for PBT prior to neck dissection may be helpful in identifying the head and neck cancer patients in whom preoperative ordering of cross-matched blood is required or who could benefit from alternative means, such as preoperative autologous blood donation. LEVEL OF EVIDENCE: 4. PMID- 26371774 TI - Metastatic Breast Cancer in Medication-Related Osteonecrosis Around Mandibular Implants. AB - BACKGROUND: Many authors have considered dental implants to be unrelated to increased risk of medication-related osteonecrosis of the jaw (MRONJ). Nevertheless, more recently, more cases of peri-implant MRONJ (PI-MRONJ) have been described, thus becoming a challenging health problem. Also, metastatic cancer deposits are not infrequently found at peri-implant sites and this may represent an additional complication for such treatments. We present the case of a breast cancer patient with PI-MRONJ, presenting a clinically and radiologically undetected metastasis within the necrotic bone, and highlight the necessity of an accurate histopathological analysis. CASE REPORT: A 66-year-old female patient, who had received intravenous bisphosphonates for bone breast cancer metastases, came to our attention for a non-implant surgery-triggered PI-MRONJ. After surgical resection of the necrotic bone, conventional and immunohistochemical examinations were performed, which showed breast cancer deposits within the necrotic bone. CONCLUSIONS: Cancer patients with metastatic disease, who are undergoing bisphosphonate treatment, may develop unusual complications, including MRONJ, which is a site at risk for hosting additional metastatic deposits that may be clinically and radiologically overlooked. Such risk is increased by previous or concomitant implant procedures. Consequently, clinicians should be prudent when performing implant surgery in cancer patients with advanced-stage disease and consider the possible occurrence of peri-implant metastases while planning adequate treatments in such patients. PMID- 26371775 TI - Pretreatment depression as a prognostic indicator of survival and nutritional status in patients with head and neck cancer. AB - BACKGROUND: The emotional status of cancer patients is associated with disease course and treatment outcomes. In this study, the authors evaluated associations between the presence of pretreatment depression and pretreatment quality of life (QOL), nutritional status, and survival outcomes in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: For this prospective study, 241 patients with previously untreated HNSCC who underwent curative treatments were enrolled. Patients completed the Beck Depression Inventory (BDI)-II, the European Organization for Research and Treatment of Cancer (EORTC) 30-item Core QOL Questionnaire (QLQ-C30), and the EORTC QLQ Head and Neck Cancer module (QLQ H&N35). EORTC QLQ scores were compared between depressive and nondepressive patients, as determined according to pretreatment BDI-II scores >= 14 and <14, respectively. Univariate and multivariate analyses were performed to assess whether the presence of depression was associated with overall survival, disease free survival (DFS), or posttreatment changes in nutritional status and laboratory data. RESULTS: Pretreatment depression was present in 60 patients (24.9%). In depressive and nondepressive patients, the 3-year overall survival rates were 70.8% and 82.7%, respectively (P = .045), and the 3-year DFS rates were 63.5% and 79.1%, respectively (P = .015). After controlling for clinical factors, the presence of depression was predictive of 3-year DFS (P = .032). EORTC QLQ-C30 and QLQ-HN35 scores on all items except feeding tube, nutritional supplement, and problem with mouth opening differed between depressive and nondepressive patients (P < .05). Depressive patients had lower pretreatment serum albumin levels than nondepressive patients (P < .05). CONCLUSIONS: There was a significant correlation between pretreatment depression and pretreatment QOL, nutritional status, and survival outcomes in patients with HNSCC. PMID- 26371776 TI - Outcomes and complications of osseointegrated hearing aids in irradiated temporal bones. AB - OBJECTIVES/HYPOTHESIS: To compare the complication rate for osseointegrated hearing aids (OIHA) in patients with or without irradiation. STUDY DESIGN: Retrospective case review. METHODS: We studied patients with OIHAs implanted between January 1, 2005, and July 15, 2013 in a tertiary university center with a referral otology and neurotology practice. Demographics, history of oncologic surgery, follow-up length after OIHA implantation, radiation history and dosage, postoperative complications, and chronologic relationship between oncologic resection, OIHA implantation, and irradiation were reviewed to collect information. Soft tissue complications were graded according to a modified Holgers classification. RESULTS: The study included 48 patients. Twenty-nine patients (32 implants) did not undergo radiotherapy and 19 patients (19 implants) did. In the radiotherapy group, six patients had OIHAs implanted before radiotherapy, and 13 had OIHAs implanted in irradiated bone. Of these 13 patients, one had OIHA implanted during primary oncologic surgery; 11 had OIHA implanted during secondary surgery; and one patient did not have oncologic surgery. Patients with both OIHA implantation and radiotherapy had more complications than patients without radiotherapy (31.6% vs. 24.1%, P > 0.05) and more major complications than patients without radiotherapy (26.3% vs. 3.4%, P > 0.05). Patients with OIHAs implanted before radiotherapy did not have any complications. There were significantly fewer and less severe complications in patients with OIHAs implanted during primary oncologic resection than in patients with OIHAs implanted secondarily (0/8 vs. 8/11, P < 0.05). CONCLUSIONS: The rate and severity of complications of OIHAs can be minimized by implanting the device before irradiation, ideally at the time of primary oncologic surgery. LEVEL OF EVIDENCE: 4. Laryngoscope, 126:1187-1192, 2016. PMID- 26371777 TI - New frontiers in proton therapy: applications in breast cancer. AB - PURPOSE OF REVIEW: The aim of this article is to review published data on proton therapy in the multimodality treatment of breast cancer so as to provide an overview of the advantages and critical issues relating to this irradiation modality. RECENT FINDINGS: In-silico studies show a clear advantage in terms of dose homogeneity to the target and dose reduction to the non-target structures including heart, lungs, and healthy breast tissues. Clinical studies have shown the feasibility of proton therapy in breast cancer and allowed optimizing the technique by using multiple beams and intensity modulation. SUMMARY: Proton therapy is able to optimize the dose to the target and to reduce the irradiation of the healthy tissues. Clinical studies are expected to show a decreased risk of late side effects with potential improvement of the quality of life of breast cancer patients. PMID- 26371778 TI - Cognitive outcome after radiotherapy in brain tumor. AB - PURPOSE OF REVIEW: Survival of brain tumor patients has increased with improvements in cancer treatments. However, treatments like radiotherapy can be neurotoxic and thus new end-points in clinical trials, as well as in individual management, have appeared. This article reviews the cognitive outcomes after radiotherapy in brain tumor patients, focusing on radiation-induced impairments, and then discusses actual cognitive assessment limitations. RECENT FINDINGS: Although physiopathology of radiation-induced cognitive impairments remains elusive, a general course can be described as acute, early-delayed, and late delayed effects corresponding to different processes. The last is of high interest because the related impairments are irreversible. In this context, a cognitive assessment should be performed as often as possible, but actual tools are unfortunately not developed. Nevertheless, with respect to neuro-oncologic specificities, new cognitive tools could be developed to overcome these limitations. SUMMARY: Improvements in neuropsychologic assessment for brain tumor patients are urgently needed. A dynamic vision of radiation-induced cognitive impairments appears inevitable and should lead to a change in actual considerations about neurotoxicity follow-up. PMID- 26371779 TI - Mechanisms of breast cancer resistance to anthracyclines or taxanes: an overview of the proposed roles of noncoding RNA. AB - PURPOSE OF REVIEW: Anthracyclines and taxanes are the two most active classes of cytotoxic agents that are commonly used for the treatment of breast cancer. However, resistance to these agents has become a major clinical obstacle. The aim of the present review is to define the roles of noncoding RNA (ncRNA) in breast cancer progression and the development of chemotherapy resistance. The ultimate goal is to exploit ncRNAs as new therapeutic tools to overcome resistance. RECENT FINDINGS: Two important types of ncRNA include microRNA (miRNA) and long noncoding RNA (lncRNA). Both miRNA and lncRNA have recently impacted the field of breast cancer research as important pieces in the mechanistic puzzle of the genes and pathways involved in breast cancer development and progression. SUMMARY: Herein, we review the roles of miRNA and lncRNA in breast cancer progression and the development of chemotherapy resistance. Future research should include identification of ncRNAs that could be potential therapeutic targets in chemotherapy-resistant tumors, as well as ncRNA biomarkers that facilitate more tumor-specific treatment options for chemotherapy-resistant breast cancer patients. PMID- 26371780 TI - Recent developments and controversies in primary central nervous system lymphoma. AB - PURPOSE OF REVIEW: Primary central nervous system lymphoma (PCNSL) is a rare tumor, and its optimal management is a matter of controversy. Recent developments of collaborative groups devoted to PCNSL have allowed to conduct randomized trials addressing important issues. In addition, genome wide analysis provided new insights in the PCNSL tumorigenesis. RECENT FINDINGS: The purpose of the present review is to focus on the most recent findings in the management and the biological advances of PCNSL. SUMMARY: Cumulating data challenge the role of consolidation radiotherapy after high-dose methotrexate-based polychemotherapy, especially in the elderly, in order to reduce delayed neurotoxicity, support intensive chemotherapy with autologous stem cell transplantation as a therapeutic option in PCNSL, confirm the interest for adding rituximab in the initial treatment, and suggest the importance of B-cell receptor/Toll-like receptor/nuclear factor kappa B signaling pathway activation in PCNSL as a promising target for novel therapies. PMID- 26371781 TI - Intralymphatic Spread Is a Common Finding in Cutaneous CD30+ Lymphoproliferative Disorders. AB - An intralymphatic variant of the cutaneous CD30 lymphoproliferative disorders (cutaneous anaplastic large cell lymphoma [ALCL] and lymphomatoid papulosis [LyP]) has been described recently. We retrieved 60 cases of ALCL of the skin (primary cutaneous: 37; cases with concomitant involvement of 1 regional lymph node: 4; skin involvement from systemic disease: 4; cases with staging results unknown: 15) and 16 cases of LyP, to evaluate the presence of lymphatic vessel involvement by neoplastic cells. A D2-40 immunohistochemical staining was used to highlight lymphatic vessels. Lymphatic vessel involvement was found in 36 cases (60%) of ALCL (primary cutaneous: 24; concomitant: 3; secondary cutaneous: 4; staging unknown: 5), and in 6 cases (37.5%) of LyP. Follow-up data, available in 28 patients with ALCL and 11 with LyP, suggested that lymphatic vessel involvement had no negative prognostic implication. Our study demonstrates that cutaneous CD30 lymphoproliferative disorders are frequently characterized by involvement of the lymphatic vessels. The intralymphatic variant of ALCL and LyP may be explained, at least in part, by a particular lymphotropism of the neoplastic cells of cutaneous CD30 lymphoproliferative disorders. PMID- 26371782 TI - Angiosarcoma Arising in Chronic Expanding Hematoma: Five Cases of an Underrecognized Association. AB - Little is known about the etiology or pathogenesis of angiosarcoma (AS). We describe a series of 5 cases of AS arising in chronic expanding hematomas. Inclusion criteria were the presence of a hematoma of at least 1-year duration and a thick fibrous wall surrounding the hematoma. Patients were 4 men and 1 woman; ages ranged from 43 to 71 years. Locations were the thigh (3), chest wall (1), and pelvic soft tissue involving the ischial bone (1). Hematoma duration ranged from 2 to 25 years. All cases had large cystic hematomas >10 cm; 2 had prior radiation. Thick fibrous walls surrounded the hematomas, with foci of hemosiderin and foamy histiocytes. Wall thickness ranged from 0.2 to 1.0 cm and varied within lesions. All AS were epithelioid, and in 3 cases the tumor invaded through the cyst wall. Immunoreactive nuclear c-myc was noted in 3/3 cases available for testing. Follow-up disclosed 4 patients developed metastatic disease, 3 of whom died of disease, 4, 8, and 15 months after diagnosis; the fourth patient is alive without disease after chemotherapy at 59 months. One patient without metastases is alive without disease 18 months after diagnosis; this tumor was confined to the cyst without penetration through the wall. We identified 4 similar cases in the literature, 3 as individual case reports (all epithelioid AS), and 1 as part of a series of AS. To our knowledge, this is the first series of AS arising in chronic expanding hematomas. Recognition of this unusual complication should alert clinicians to provide periodic clinical follow up to these patients and to biopsy any case with sudden or uncontrolled enlargement. We recommend that excised chronic hematomas be well sampled histologically to search for AS and, if identified, to determine its extent and invasiveness. PMID- 26371783 TI - Novel PAX3-NCOA1 Fusions in Biphenotypic Sinonasal Sarcoma With Focal Rhabdomyoblastic Differentiation. AB - Sarcomas arising in the sinonasal region are uncommon and encompass a wide variety of tumor types, including the newly described biphenotypic sinonasal sarcoma (BSNS), which is characterized by a monomorphic spindle cell proliferation with dual neural and myogenic phenotypes. Most BSNSs harbor a pathognomonic PAX3-MAML3 fusion driven by t(2;4)(q35;q31.1), whereas the alternative fusion partner gene remains unidentified in a subset of PAX3 rearranged cases. As NCOA1 on 2p23 is a known partner in PAX3-related fusions in other tumor types (ie, alveolar rhabdomyosarcoma), we investigated its status by fluorescence in situ hybridization (FISH) and reverse transcription polymerase chain reaction assays in 2 BSNS cases showing only PAX3 gene rearrangements. Novel PAX3-NCOA1 fusions were identified in these 2 index cases showing an inv(2)(q35p23) by FISH and confirmed by reverse transcription polymerase chain reaction. Five additional BSNS cases with typical morphology were studied by FISH, revealing a PAX3-MAML3 fusion in 4 cases and only PAX3 rearrangement in the remaining case without abnormalities in MAML3 or NCOA1 gene. Except for 1 case with surface ulceration, all other tumors lacked increased mitotic activity or necrosis, and all cases immunohistochemically coexpressed S100 protein and actin, but lacked SOX10 reactivity. Interestingly, the 2 PAX3-NCOA1-positive cases showed desmin reactivity and displayed a small component of rhabdomyoblastic cells, which were not seen in the more common PAX3-MAML3 fusion cases. In conclusion, we report a novel PAX3-NCOA1 fusion in BSNS, which appears to be associated with focal rhabdomyoblastic differentiation and should be distinguished from PAX3-NCOA1-positive alveolar rhabdomyosarcoma or malignant Triton tumor. SOX10 immunohistochemistry is a useful marker in distinguishing BSNS from peripheral nerve sheath tumors. PMID- 26371784 TI - Role of the Biomarker p16 in Downgrading -IN 2 Diagnoses and Predicting Higher grade Lesions. AB - In 2012, the College of American Pathologists and American Society for Colposcopy and Cervical Pathology published the "LAST" recommendations for histopathology reporting of human papilloma virus-related squamous lesions of the lower anogenital tract, including the use of a 2-tier nomenclature (low-grade squamous intraepithelial lesion/high-grade squamous intraepithelial lesion [LSIL/HSIL]) and expanded use of the biomarker p16 to classify equivocal lesions as either precancer (HSIL) or low-grade lesions (LSIL)/non-human papilloma virus changes. We aimed to determine (1) the frequency with which the poorly reproducible diagnosis of intermediate-grade (-IN 2) lesion in the lower anogenital tract would be downgraded on the basis of p16 results, and (2) whether p16 status was predictive of subsequent higher-grade lesions. A total of 200 specimens diagnosed as an intermediate-grade (-IN 2) lesion of the cervix (168), vagina (2), vulva (2), and anus (28) were reviewed and immunostained for p16. Slides were independently reviewed by 2 pathologists, with discrepant p16 interpretations adjudicated by a third pathologist. Of the 200 cases, 32% were negative for p16. Among the 166 patients with subsequent pathology (including 131 excisions), 26.2% of p16-positive cases versus 4.4% of p16-negative cases were associated with a subsequent diagnosis of HSIL (-IN 3) or worse (P=0.002). Reproducibility of the biopsy diagnosis was fair, with no significant difference with the addition of p16 or using 2 versus 3 tiers. In 11.5% of cases, there was discordance in p16 interpretation (kappa 0.735, good agreement). The results indicate that using the Lower Anogenital Squamous Terminology recommendations would result in approximately one third of equivocal (-IN 2) diagnoses being downgraded to LSIL over 1 year in a busy academic practice. The significant association of p16 expression with a higher risk for HSIL on a subsequent specimen suggests that use of p16 to adjudicate equivocal (-IN 2) diagnoses in lower anogenital tract specimens as either LSIL or HSIL would likely predict lesion grade more accurately and avoid unnecessary excisional procedures. PMID- 26371785 TI - Sarcomatoid Peritoneal Mesothelioma: Clinicopathologic Correlation of 13 Cases. AB - Peritoneal mesothelioma is rare, and the sarcomatoid variant is more infrequent, with <30 cases reported to date in the literature. Several case series have described the morphologic features of sarcomatoid peritoneal mesothelioma (SPe); however, the clinicopathologic features are not well characterized. To our knowledge, this is the first large series reporting the clinicopathologic features of SPe. We reviewed our database of 3106 malignant mesothelioma cases. Of 248 peritoneal mesotheliomas, 15 (4%) were sarcomatoid variant (0.5% of all mesotheliomas). Only cases with 100% sarcomatoid morphology diagnosed by open surgical biopsy and/or autopsy were included. Thus, 4 cases were excluded leaving 11 cases of SPe. Two additional cases of SPe previously published by 1 of the authors (V.L.R.), not included in the database, are added yielding 13 cases total. The median age at diagnosis was 66 years (range=48 to 85 y), and there was a male predominance (M:F=3.25:1). Survival from date of diagnosis to date of death was 5 months (range=0 to 12 mo). The most common presenting symptom was abdominal pain, and 3 of 4 women were suspected to have cholecystitis/cholelithiasis. All cases stained positive for cytokeratins, and 2 contained heterologous elements. Seven cases had objective markers of asbestos exposure, and 2 additional cases had occupations strongly associated with mesothelioma. Two cases with alleged household contact exposures could not be confirmed to be asbestos related by lung fiber analysis. SPe is a rare variant of mesothelioma attributed to asbestos exposure in 69% of our cases. PMID- 26371786 TI - Sexual Behavior Patterns and PrEP Dosing Preferences in a Large Sample of North American Men Who Have Sex With Men. AB - INTRODUCTION: Pre-exposure prophylaxis (PrEP), taken as a single daily coformulated pill containing tenofovir -emtricitabine, is a promising intervention to reduce the likelihood of HIV acquisition in at-risk individuals, including men who have sex with men. Little is known about the acceptability of less than daily, intermittent PrEP regimens. METHODS: We conducted an online survey of North American men who have sex with men to characterize their sexual frequency and planning behaviors and correlate these with PrEP dosing preferences. RESULTS: Of the 3217 respondents who completed the survey, 46% reported engaging in unplanned condomless anal intercourse (CAI) at least once in previous 3 months and 8% reported engaging in CAI more than once per week. In multivariable analysis, reporting unplanned CAI was associated with lower educational level, identifying as homosexual/gay as compared with bisexual, being in a monogamous relationship, having a higher self-perceived risk of HIV acquisition, reporting higher income, engaging in CAI more than five times in the last 3 months, and not having visited a health care provider in the previous year. Frequent CAI (>1 time per week) was associated with being younger, identifying as homosexual/gay as compared with bisexual, being in a monogamous relationship, and having a higher self-perceived risk of HIV. Having only planned sex over the last 3 months was associated with a preference for event-based PrEP, whereas having frequent or unplanned CAI was associated with a preference for daily or time-driven PrEP regimens, respectively. CONCLUSION: Our findings suggest that preferences for different PrEP regimens are associated with the sexual frequency and planning behaviors of potential users. PMID- 26371787 TI - Reproducibility, Reliability, and Validity of Fuchsin-Based Beads for the Evaluation of Masticatory Performance. AB - PURPOSE: Rehabilitation of masticatory function is inherent to prosthodontics; however, despite the various techniques for evaluating oral comminution, the methodological suitability of these has not been completely studied. The aim of this study was to determine the reproducibility, reliability, and validity of a test food based on fuchsin beads for masticatory function assessment. MATERIALS AND METHODS: Masticatory performance was evaluated in 20 dentate subjects (mean age, 23.3 years) using two kinds of test foods and methods: fuchsin beads and ultraviolet-visible spectrophotometry, and silicone cubes and multiple sieving as gold standard. Three examiners conducted five masticatory performance trials with each test food. Reproducibility of the results from both test foods was separately assessed using the intraclass correlation coefficient (ICC). Reliability and validity of fuchsin bead data were measured by comparing the average mean of absolute differences and the measurement means, respectively, regarding silicone cube data using the paired Student's t-test (alpha = 0.05). RESULTS: Intraexaminer and interexaminer ICC for the fuchsin bead values were 0.65 and 0.76 (p < 0.001), respectively; those for the silicone cubes values were 0.93 and 0.91 (p < 0.001), respectively. Reliability revealed intraexaminer (p < 0.001) and interexaminer (p < 0.05) differences between the average means of absolute differences of each test foods. Validity also showed differences between the measurement means of each test food (p < 0.001). CONCLUSIONS: Intra- and interexaminer reproducibility of the test food based on fuchsin beads for evaluation of masticatory performance were good and excellent, respectively; however, the reliability and validity were low, because fuchsin beads do not measure the grinding capacity of masticatory function as silicone cubes do; instead, this test food describes the crushing potential of teeth. Thus, the two kinds of test foods evaluate different properties of masticatory capacity, confirming fushsin beads as a useful tool for this purpose. PMID- 26371788 TI - Special Section: Balancing Conservation and Development to Preserve China's Biodiversity. PMID- 26371789 TI - Analysis of the association between polymorphisms in MMP2, MMP3, MMP9, MMP20, TIMP1, and TIMP2 genes with white spot lesions and early childhood caries. AB - BACKGROUND: Matrix metalloproteinases and their inhibitors might be involved in enamel formation. AIM: This study aimed to evaluate the association between polymorphisms in MMP2, MMP3, MMP9, MMP20, TIMP1, and TIMP2 with white spot lesions (WSL) and early childhood caries (ECC). DESIGN: A cross-sectional study was performed on 786 children aged from 2 to 6 years in Brazil. After clinical evaluation, they were classified into groups with disease (the presence of WSL and/or ECC) and without disease (the absence of WSL or ECC). Genotyping of the selected polymorphisms was carried out with TaqMan real-time PCR, using genomic DNA extracted from buccal cells. Allele and genotype frequencies were compared between groups. Chi-square test, odds ratio (OR), and logistic regression were used (P <= 0.05). RESULTS: The dmft score was 1.3 (SD: 2.4), and 41.34% of the children have at least one caries lesion. In MMP9, the GG genotype was more frequent in the group without disease (P = 0.006). In a recessive model, WSL was associated with the marker rs1711437 in MMP20 (P = 0.019; OR = 1.20, 95% CI 1.02 1.42). The marker rs1784418 in MMP20 showed an association between the allele G distribution for the WSL group (P = 0.020; OR = 0.73, 95% CI 0.55-0.96). CONCLUSION: MMP9 and MMP20 are involved in WSL and ECC development. PMID- 26371791 TI - Historical loss thinking and symptoms of depression are influenced by ethnic experience in American Indian college students. AB - OBJECTIVE: Recent research has indicated that historical loss may play an important role in the experience of depression symptoms in American Indian/Alaska Native people. Increased frequency of historical loss thinking has been related to symptoms of depression and other pervasive psychological outcomes (i.e., substance abuse) in American Indian and Canadian First Nations communities. The current study investigated how aspects of ethnic minority experience relate to the incidence of historical loss thinking and symptoms of depression in American Indian adults. METHOD: Data are presented from 123 self-identified American Indian college students (ages 18-25, 67.50% female) who participated in the study in return for course credit and/or entrance into a raffle for gift cards. Participants completed the Adolescent Historical Loss Scale (AHLS), Scale of Ethnic Experiences (SEE), and the Center for Epidemiologic Studies-Depression Scale (CES-D). Indirect effects of ethnic experience on symptoms of depression through historical loss thinking were calculated with nonparametric bootstrapping procedures. RESULTS AND CONCLUSIONS: Results indicated that a strong ethnic identification, desire to predominantly socialize with other American Indians, and perceptions of discrimination were associated with increased historical loss thinking. Feelings of comfort and assimilation with the mainstream American culture were negatively related to historical loss thinking. Only perception of discrimination was directly related to symptoms of depression; however, ethnic identification and the preference to predominantly socialize with other American Indians were both indirectly related to elevated depressive symptoms through increased historical loss thinking. The clinical implications for these results are discussed. (PsycINFO Database Record PMID- 26371792 TI - White fear, dehumanization, and low empathy: Lethal combinations for shooting biases. AB - OBJECTIVES: A growing number of studies have documented the existence racial shooting biases against Black versus White targets (Correll et al., 2002). Little is known about individual differences that may moderate these biases. The goals of this study were to examine (a) whether White participants' fear of racial/ethnic minorities is associated with racial shooting biases, and (b) whether dehumanization and empathy moderate this effect. METHOD: Participants (N = 290) completed a dehumanization implicit association test and simulated shooting task, then reported their fear of racial minorities (i.e., White fear) and empathic ability. RESULTS: We found that (a) individuals high in White fear showed a shooting bias, such that they had a lower threshold for shooting Black relative to White and East Asian targets, (b) Dehumanization moderated the White fear and shooting bias relation, such that individuals high in White fear and high in dehumanization had a significantly more liberal shooting threshold for Black versus White targets, and (c) Empathy moderated the White fear and shooting bias relation, such that people who were high in White fear and low in empathic ability had a more liberal shooting threshold for Black versus White targets. In sum, fearing racial/ethnic minorities can have devastating shooting bias outcomes for Black individuals, but this effect is stronger when people also dehumanize Black individuals, and weaker when people have high empathy. CONCLUSIONS: These findings contribute to the literature by identifying theory driven moderators that identify both risk and protective factors in predicting racial shooting biases. (PsycINFO Database Record PMID- 26371790 TI - Spatially organized differentiation of mesenchymal stem cells within biphasic microparticle-incorporated high cell density osteochondral tissues. AB - Giving rise to both bone and cartilage during development, bone marrow-derived mesenchymal stem cells (hMSC) have the unique capacity to generate the complex tissues of the osteochondral interface. Utilizing a scaffold-free hMSC system, biphasic osteochondral constructs are incorporated with two types of growth factor-releasing microparticles to enable spatially organized differentiation. Gelatin microspheres (GM) releasing transforming growth factor-beta1 (TGF-beta1) combined with hMSC form the chondrogenic phase. The osteogenic phase contains hMSC only, mineral-coated hydroxyapatite microparticles (MCM), or MCM loaded with bone morphogenetic protein-2 (BMP-2), cultured in medium with or without BMP-2. After 4 weeks, TGF-beta1 release from GM within the cartilage phase promotes formation of a glycosaminoglycan- and type II collagen-rich matrix, and has a local inhibitory effect on osteogenesis. In the osteogenic phase, type X collagen and osteopontin are produced in all conditions. However, calcification occurs on the outer edges of the chondrogenic phase in some constructs cultured in media containing BMP-2, and alkaline phosphatase levels are elevated, indicating that BMP-2 releasing MCM provides better control over region-specific differentiation. The production of complex, stem cell-derived osteochondral tissues via incorporated microparticles could enable earlier implantation, potentially improving outcomes in the treatment of osteochondral defects. PMID- 26371793 TI - Bronchogenic cancer: It still exists. AB - OBJECTIVES/HYPOTHESIS: Branchial cleft cysts rank among the most common differential diagnoses of cystic cervical masses. Rarely, classic cystic structures exhibit a squamous cell carcinoma differentiation that represents a bronchogenic carcinoma. The existence of bronchogenic carcinoma is controversial due to the lack of systematic immunohistologic workup. The present study aimed to identify the clinical and immunohistologic features of bronchogenic carcinoma to clearly distinguish this entity from other cystic cervical masses. METHODS: Immunohistologic (epidermal growth factor receptor; cytokeratin 5, 6, 7, 13; and p16) and epidemiologic assessments were performed for branchial cleft cysts (n = 63), bronchogenic carcinomas (n = 5), cystic metastasized oropharyngeal carcinomas (n = 97), and carcinomas of unknown primary (n = 51). The study was conducted as a retrospective case series study with comparison. RESULTS: The patients with bronchogenic carcinomas differed significantly in age and in the number of involved lymph nodes compared with the cystic metastasized oropharyngeal carcinoma (and carcinoma of unknown primary) patients. Regular histologic wall structures were only observed in the bronchogenic carcinomas and branchial cleft cysts. Solitary cytokeratin-7 staining was only observed in the bronchogenic carcinomas, and all of the bronchogenic carcinomas were p16 negative. CONCLUSIONS: The existence of bronchogenic carcinoma seems to be plausible based on clinical findings. Cytokeratin-7 and p16 staining might be helpful in the diagnostic workflow. LEVEL OF EVIDENCE: 4 Laryngoscope, 126:638 642, 2016. PMID- 26371794 TI - The effect of culture on pain sensitivity. AB - Cross-cultural differences in pain sensitivity have been identified in pain-free subjects as well as in chronic pain patients. The aim was to assess the impact of culture on psychophysical measures using mechanical and electrical stimuli in patients with temporomandibular disorder (TMD) pain and pain-free matched controls in three cultures. This case-control study compared 122 female cases of chronic TMD pain (39 Saudis, 41 Swedes and 42 Italians) with equal numbers of age and gender-matched TMD-free controls. Pressure pain threshold (PPT) and tolerance (PPTo) were measured over one hand and two masticatory muscles. Electrical perception threshold and electrical pain threshold (EPT) and tolerance (EPTo) were recorded between the thumb and index fingers. Italian females reported significantly lower PPT in the masseter muscle than other cultures (P < 0.001) and in the temporalis muscle than Saudis (P = 0.003). Swedes reported significantly higher PPT in the thenar muscle than other cultures (P = 0.017). Italians reported significantly lower PPTo in all muscles than Swedes (P <= 0.006) and in the masseter muscle than Saudis (P < 0.001). Italians reported significantly lower EPTo than other cultures (P = 0.01). Temporomandibular disorder cases, compared to TMD-free controls, reported lower PPT and PPTo in all the three muscles (P < 0.001). This study found cultural differences between groups in the PPT, PPTo and EPTo. Overall, Italian females reported the highest sensitivity to both mechanical and electrical stimulation, while Swedes reported the lowest sensitivity. Mechanical pain thresholds differed more across cultures than did electrical pain thresholds. Cultural factors may influence response to type of pain test. PMID- 26371796 TI - Is there a purely biological core to pain experience? PMID- 26371795 TI - Test-retest reliability of pain-related functional brain connectivity compared with pain self-report. AB - Test-retest reliability, or reproducibility of results over time, is poorly established for functional brain connectivity (fcMRI) during painful stimulation. As reliability informs the validity of research findings, it is imperative to examine, especially given recent emphasis on using functional neuroimaging as a tool for biomarker development. Although proposed pain neural signatures have been derived using complex, multivariate algorithms, even the reliability of less complex fcMRI findings has yet to be reported. This study examined the test retest reliability for fcMRI of pain-related brain regions, and self-reported pain (through visual analogue scales [VASs]). Thirty-two healthy individuals completed 3 consecutive fMRI runs of a thermal pain task. Functional connectivity analyses were completed on pain-related brain regions. Intraclass correlations were conducted on fcMRI values and VAS scores across the fMRI runs. Intraclass correlations coefficients for fcMRI values varied widely (range = -.174-.766), with fcMRI between right nucleus accumbens and medial prefrontal cortex showing the highest reliability (range = .649-.766). Intraclass correlations coefficients for VAS scores ranged from .906 to .947. Overall, self-reported pain was more reliable than fcMRI data. These results highlight that fMRI findings might be less reliable than inherently assumed and have implications for future studies proposing pain markers. PMID- 26371800 TI - Early recognition of anti-N-methyl-D-aspartate receptor encephalitis in psychiatric patients. PMID- 26371801 TI - Reply: To PMID 25338667. PMID- 26371802 TI - Is all psychiatry social? PMID- 26371803 TI - Reply: To PMID 25604122. PMID- 26371804 TI - Protein Adsorption From Biofluids on Silica Nanoparticles: Corona Analysis as a Function of Particle Diameter and Porosity. AB - A study on the adsorption of proteins from fetal bovine serum (FBS) on spherical dense and mesoporous silica nanoparticles with a wide range of diameters, from 70 to 900 nm, is presented. Monodisperse populations of particles with a range of diameters were obtained through modifications of the Stober method. Extensive characterization of the particles was then performed using N2 physisorption, TEM, DLS, and zeta-potential. Following serum exposure, proteomic evaluation in concert with thermogravimetric analysis revealed the associated concentrations of each protein identified in the hard corona. Small particles adsorbed the largest amount of protein, due to their larger external surface area. Proteins with low molecular weights (<50 kDa) constituted the majority of the protein corona, totaling between 60 and 80% of the total mass of adsorbed protein. Here, the higher surface curvature of small particles favors the enrichment of smaller proteins. Porosity does not promote protein adsorption but improves deposition of the low molecular weight protein fraction due to the size-exclusion effect related to pore diameter. These results have important implications for the use of dense and porous silica nanoparticles in biomedical applications. PMID- 26371805 TI - A Small Molecule That Switches a Ubiquitin Ligase From a Processive to a Distributive Enzymatic Mechanism. AB - E3 ligases are genetically implicated in many human diseases, yet E3 enzyme mechanisms are not fully understood, and there is a strong need for pharmacological probes of E3s. We report the discovery that the HECT E3 Nedd4-1 is a processive enzyme and that disruption of its processivity by biochemical mutations or small molecules switches Nedd4-1 from a processive to a distributive mechanism of polyubiquitin chain synthesis. Furthermore, we discovered and structurally characterized the first covalent inhibitor of Nedd4-1, which switches Nedd4-1 from a processive to a distributive mechanism. To visualize the binding mode of the Nedd4-1 inhibitor, we used X-ray crystallography and solved the first structure of a Nedd4-1 family ligase bound to an inhibitor. Importantly, our study shows that processive Nedd4-1, but not the distributive Nedd4-1:inhibitor complex, is able to synthesize polyubiquitin chains on the substrate in the presence of the deubiquitinating enzyme USP8. Therefore, inhibition of E3 ligase processivity is a viable strategy to design E3 inhibitors. Our study provides fundamental insights into the HECT E3 mechanism and uncovers a novel class of HECT E3 inhibitors. PMID- 26371806 TI - Chronic Rhinosinusitis: More Than Just "Asthma of the Upper Airway". PMID- 26371807 TI - "B" for Bad, Beneficial, or Both? Lung Lymphoid Neogenesis in Chronic Obstructive Pulmonary Disease. PMID- 26371808 TI - Low-Flow Extracorporeal Carbon Dioxide Removal. Moving Closer to Reality. PMID- 26371809 TI - Solving the Conundrum: Immunogenetics of Sarcoidosis. PMID- 26371810 TI - Noninvasive Quantitative Imaging-based Biomarkers and Lung Cancer Screening. PMID- 26371811 TI - Associations between Obstructive Sleep Apnea and Glucose Metabolism. More Than Meets the Eye. PMID- 26371812 TI - Update in Cystic Fibrosis 2014. PMID- 26371813 TI - Update in Viral Infections 2014. PMID- 26371814 TI - Hypereosinophilic Pulmonary Carcinomatous Lymphangitis Mimicking Acute Eosinophilic Pneumonia. PMID- 26371815 TI - Decreased Cytotoxic T-Lymphocyte Antigen 4 Expression on Regulatory T Cells and Th17 Cells in Sarcoidosis: Double Trouble? PMID- 26371816 TI - Oxygen Delivery and Consumption Are Independent: Evidence from Venoarterial Extracorporeal Membrane Oxygenation in Resuscitated Children. PMID- 26371817 TI - Further Progress in Understanding Fibrosing Mediastinitis. PMID- 26371818 TI - Reply: Further Progress in Understanding Fibrosing Mediastinitis. PMID- 26371819 TI - The Worldwide End-of-Life Practice for Patients in Intensive Care Units Study: Adding Africa. PMID- 26371820 TI - Reply: The Worldwide End-of-Life Practice for Patients in Intensive Care Units Study: Adding Africa. PMID- 26371821 TI - Expression of Concern: TLR4 Is Necessary for Hyaluronan-mediated Airway Hyperresponsiveness after Ozone Inhalation; c-Kit Is Essential for Alveolar Maintenance and Protection from Emphysema-like Disease in Mice. PMID- 26371822 TI - Right Ventricular Arrhythmogenic Dysplasia in Cardiac Arrest. An Echocardiographic Pattern Not to Forget. PMID- 26371823 TI - Continuous Positive Airway Pressure for Adults with Obstructive Sleep Apnea. PMID- 26371824 TI - 2D vanadium doped manganese dioxides nanosheets for pseudocapacitive energy storage. AB - Ultrathin two-dimensional (2D) crystals have been predicted to have high electrochemical activity because nearly all active atoms are exposed to the electrolytes, which offers great potential for energy storage. However, to construct layered structure metal oxides, simplifying the synthetic methods and improving the electronic conductivity remain a challenge. Herein, we synthesized 2D vanadium doped manganese oxides through a facile hydrothermal method. Vanadium dopant is also used as a template agent for the formation of nanosheet-shaped MnO2, further leading to high specific surface area as well as significant enhancement of the electronic conductivity, as confirmed by the first-principle calculations and four-point probe method. For the sake of a shortened ion transport distance and enhanced electronic conductivity, V-doped MnO2 nanosheets display an excellent electrochemical performance as a supercapacitor electrode. PMID- 26371825 TI - Solvothermal synthesis of superhydrophobic hollow carbon nanoparticles from a fluorinated alcohol. AB - A new and simple method of synthesizing fluorinated carbon at the gram scale is presented by reacting a fluorinated alcohol with sodium at elevated temperatures in a sealed Teflon reactor. The resulting carbon nanoparticles are around 100 nm in diameter, and display a hollow shell morphology, with a significant amount of fluorine doped into the carbon. The nanoparticles disperse easily in ethanol, and are thermally stable up to 400 degrees C and 450 degrees C under air and nitrogen, respectively. The nanoparticle dispersion was printed onto various substrates (paper, cloth, silicon), inducing superhydrophobicity. PMID- 26371826 TI - A New Reaction Pathway for Bromite to Bromate in the Ozonation of Bromide. AB - Ozone is often used in the treatment of drinking water. This may cause problems if the water to be treated contains bromide as its reaction with ozone leads to the formation of bromate, which is considered to be carcinogenic. Bromate formation is a multistep process resulting from the reaction of ozone with bromite. Although this process seemed to be established, it has been shown that ozone reacts with bromite not by the previously assumed mechanism via O transfer but via electron transfer. Besides bromate, the electron-transfer reaction also yields O3(*-), the precursor of OH radicals. The experiments were set up in such a way that OH radicals are not produced from ozone self-decomposition but solely by the electron-transfer reaction. This study shows that hydroxyl radicals are indeed generated by using tBuOH as the OH radical scavenger and measuring its product, formaldehyde. HOBr and bromate yields were measured in systems with and without tBuOH. As OH radicals contribute to bromate formation, higher bromate and HOBr yields were observed in the absence of tBuOH than in its presence, where all OH radicals are scavenged. On the basis of the results presented here, a pathway from bromide to bromate, revised in the last step, was suggested. PMID- 26371827 TI - A Call to the Early Career Nanoscience Community: Now Accepting Nominations for the Nano Letters Early Career Advisory Board. PMID- 26371828 TI - Sensory reweighting is altered in adolescent patients with scoliosis: Evidence from a neuromechanical model. AB - Idiopathic scoliosis is the most frequent spinal deformity in adolescence. While its aetiology remains unclear, impairments in balance control suggest a dysfunction of the sensorimotor control mechanisms. The objective of this paper is to evaluate the ability of patients with idiopathic scoliosis to reweigh sensory information. Using a neuromechanical model, the relative sensory weighting of vestibular and proprioceptive information was assessed. Sixteen healthy adolescents and respectively 20 and 16 adolescents with mild or severe scoliosis were recruited. Binaural bipolar galvanic vestibular stimulation was delivered to elicit postural movement along the coronal plane. The kinematics of the upper body, using normalized horizontal displacement of the 7th cervical vertebra, was recorded 1s before, 2s during, and 1s following vestibular stimulation. The neuromechanical model included active feedback mechanisms that generated corrective torque from the vestibular and proprioceptive error signals. The model successfully predicted the normalized horizontal displacement of the 7th cervical vertebra. All groups showed similar balance control before vestibular stimulation; however, the amplitude (i.e., peak horizontal displacement) of the body sway during and immediately following vestibular stimulation was approximately 3 times larger in patients compared to control adolescents. The outcome of the model revealed that patients assigned a larger weight to vestibular information compared to controls; vestibular weight was 6.03% for controls, whereas it was 13.09% and 13.26% for the mild and severe scoliosis groups, respectively. These results suggest that despite the amplitude of spine deformation, the sensory reweighting mechanism is altered similarly in adolescent patients with scoliosis. PMID- 26371829 TI - Influence of orthosis on the foot progression angle in children with spastic cerebral palsy. AB - We retrospectively assessed the effect of ankle-foot orthosis (AFO) on the foot progression angle (FPA) of 97 children with spastic cerebral palsy (CP) who had undergone comprehensive computer-based gait analysis both barefoot and with their orthosis, during the same session. The physical examination results and the gait study temporal and kinematic parameters comprise the study data. We focused on the peak FPA reached during stance and swing phases and at mid-stance and mid swing, and also measured the transverse rotations of the pelvis, the femur and the tibia. AFOs improved gait, as reflected by improved temporal parameters, but they also increased internal rotation of the feet in diplegic CP children by 4.29 degrees for mid-stance, and by 3.72 degrees for mid-swing. The correlation between components of the rotational profile and FPA was significant for the diplegic group. AFOs did not produce any noteworthy differences between walking barefoot and walking with the brace in the hemiplegic group in what concerns FPA. Children with diplegic CP who use AFOs walk with increased internal FPAs in their orthoses. These findings might be explained by anatomical attributes as well as dynamic features during gait. PMID- 26371830 TI - "Stuttering" after minor head trauma. AB - Traumatic brain injury (TBI) is defined as impairment in brain function as a result of mechanical force. It is classified based on clinical findings using the Glasgow Coma Scale (GCS). Mild TBI is defined as GCS 14-15; moderate, 9-13; and severe, 3-8. Patients with the same TBI classification may have very different underlying pathology. In moderate to severe TBI, the primary pathology may include contusions, hemorrhage, diffuse axonal injury, direct cellular damage, "tearing and shearing of the tissues, loss of the blood-brain barrier, disruption of the neurochemical homeostasis and loss of the electrochemical function". Although the primary pathology associated with mild TBI may be milder versions of the same pathology associated with moderate and severe TBI, it is generally a metabolic injury. However, it is reported that 15% of patients with mild TBI and a GCS score of 14 or 15 will have an intracranial lesion; less than 1% of these require neurosurgical intervention. Although patients with mild TBI may have intracranial lesions, it is rare that the presenting and only physical examination finding is an isolated neurologic finding. Here we present a case of isolated head trauma with a single physical examination finding--expressive aphasia. PMID- 26371831 TI - Bradycardia caused by intravenous nicardipine in an elderly patient with acute ischemic infarct. AB - Nicardipine is a dihydropyridine calcium-channel blocker that is frequently used in the acute treatment of hypertension in the emergency department (ED). Reflex sympathetic tachycardia is a well-described side effect of this medication. Two experimental studies and 1 anesthesia case report, however, have previously described nicardipine-induced bradycardia as a very rare side effect. We report the case of an elderly patient with an acute ischemic stroke who developed nicardipine-induced bradycardia in the ED. PMID- 26371832 TI - Do-not-resuscitate orders among trauma patients. AB - BACKGROUND: Do-not-resuscitate (DNR) orders are an important means to communicate end-of-life wishes. Previous studies have demonstrated variable prevalence of DNR orders among hospitalized trauma patients. OBJECTIVE: This study was conducted to identify the prevalence and type of DNR orders among trauma patients and to identify associations of DNR orders with injury severity, length of stay, and whether CPR was performed in cases of cardiac arrest. METHODS: In this retrospective study, medical records were reviewed for 263 trauma patients at Miami Valley Hospital in Dayton, Ohio, in 2014 with a DNR order. RESULTS: Among 3394 trauma patients in 2014, 263 (8%) patients had a DNR order. Participants were 43% male and 57% female. The mean age was 76 (range, 16-90+) years. The most common mechanisms of injury included fall (n = 214, 81.4%) and motor vehicle collision (n = 16, 6.1%). Most DNR orders in this patient population were instituted during the hospitalization (n = 176, 67%). The most common types of advance directives included DNR order (n = 224, 85.2%), living will (n = 124, 47.2%), and durable power of health care attorney (n = 126, 47.9%). A minority of patients died during hospitalization (n = 100, 38.0%). Among patients who were deceased, 14 (14.0%) had CPR performed. CONCLUSIONS: Among trauma patients with DNR orders, most DNR orders were instituted during the hospital admission. Most deceased patients with DNR orders did not have CPR performed during the hospital stay. PMID- 26371834 TI - Dose fractionation in synchrotron radiation x-ray phase micro-tomography. AB - Phase sensitive x-ray imaging expands the applicability of standard attenuation based techniques by offering several orders of magnitude of increase in sensitivity. Due to the short wavelength, x-ray phase is not directly measurable, but has to be put in evidence by the use of phase contrast techniques. The phase can then be reconstructed from one or several phase contrast images. In this study, we consider synchrotron x-ray phase micro-computed tomography (MUCT) based on free space propagation for heterogeneous and strongly absorbing objects. This technique generally relies on acquiring several scans of the sample at different detector distances. It is also generally believed that multi-distance phase MUCT needs a higher dose input than single distance phase MUCT. The purpose of this work is to study the impact of different means of dose fractionation on the reconstructed image quality. We define different acquistion schemes in multi distance in-line phase MUCT. Previously, the exposure time at each sample-to detector distance was usually kept the same. Here, we let not only the number of distances vary but also the fraction of exposure time at each distance, the total exposure time being kept constant. Phase retrieval is performed with the mixed approach algorithm. The reconstructed MUCT images are compared in terms of accuracy, precision and resolution. In addition, we also compare the result of dose fractionated multi distance phase MUCT to single distance phase MUCT using the same total radiation dose. In the multi-distance approach, we find that using different exposure times on each distance improves the image quality in the reconstructed image. Further, we show that, despite having the same total dose delivery, the multi distance imaging method gives better image quality than the single distance method, at the cost of an additional overhead from camera displacements and reference images. We show that by optimizing the acquistion parameters in terms of number of distances and exposure time at each distance, the resulting image quality can be improved. This means that for a desired image quality, a lower radiation dose can be used. This is important especially in high resolution imaging where the radiation dose used for imaging can be very large, potentially damaging the sample. Based on the acquired data, we define an optimal protocol for use in together with the heterogeneous object mixed approach. PMID- 26371833 TI - Cost analysis of bluetongue virus serotype 8 surveillance and vaccination programmes in Austria from 2005 to 2013. AB - This study was designed to evaluate the costs between 2005 and 2013 of the national bluetongue virus (BTV) surveillance and vaccination programmes before, during and after the BTV serotype 8 (BTV-8) outbreak in Austria commencing in 2008. In addition to an assessment of the temporal development of costs, a spatial cost analysis was performed. Within the context of this study, the term 'costs' refers to actual financial expenditure and imputed monetary costs for contributions in-kind. Costs were financed directly by the private-public sectors, by the European Commission (EC), and (in-kind) by responsible national institutions and individuals (e.g. blood sampling by veterinarians). The total net cost of the BTV-8 surveillance and vaccination programmes arising from the outbreak amounted to ?22.8 million (0.86% of the national agricultural Gross Value Added), of which 32% was allocated to surveillance and 68% to the vaccination programme. Of the total programme costs, the EC supplied ?4.9 million, while the remaining costs (?18 million) were directly financed from national resources. Of the latter, ?14.5 million was classed as public costs, including ?2 million contributions in-kind, and ?3.4 million as private costs. The assessment of the costs revealed heterogeneous temporal and spatial distributions. The methodology of this analysis might assist decision makers in calculating costs for other surveillance and intervention programmes. The assessment of contributions in-kind is of importance to public authorities as it increases visibility of the available resources and shows how they have been employed. This study also demonstrates the importance of tracking changing costs per payer over time. PMID- 26371835 TI - Effects of lidocaine on regulatory T cells in atopic dermatitis. PMID- 26371836 TI - Dual response to dietary/topical steroid and proton pump inhibitor therapy in adult patients with eosinophilic esophagitis. PMID- 26371837 TI - Number, activation, and differentiation of circulating fibrocytes correlate with asthma severity. AB - BACKGROUND: A biomarker that predicts poor asthma control would be clinically useful. Fibrocytes are bone marrow-derived circulating progenitor cells that have been implicated in tissue fibrosis and T(H)2 responses in asthmatic patients. OBJECTIVE: We sought to test the hypothesis that the concentration and activation state of peripheral blood fibrocytes correlates with asthma severity. METHODS: By using fluorescence-activated cell sorting analysis, fibrocytes (CD45(+) and collagen 1 [Col1](+)) were enumerated and characterized in the buffy coats of fresh peripheral blood samples from 15 control subjects and 40 asthmatic patients. RESULTS: Concentrations of peripheral blood total (CD45(+)Col1(+)), activated (the TGF-beta transducing protein phosphorylated SMAD2/3 [p-SMAD2/3](+) or phosphorylated AKT [p-AKT](+)), and differentiated (alpha-smooth muscle actin [alpha-SMA](+)) fibrocytes were increased in asthmatic patients compared with control subjects. The increase in total and CD45(+)Col1(+)CXCR4(+) fibrocytes was primarily seen in patients with severe asthma (Global Initiative for Asthma steps 4-5) as opposed to those with milder asthma (Global Initiative for Asthma steps 1 3). In addition, numbers of circulating alpha-SMA(+) and alpha-SMA(+)CXCR4(+) fibrocytes were increased in asthmatic patients experiencing an asthma exacerbation in the preceding 12 months. A significant correlation (P < .05) was observed between CD45(+)Col1(+)CXCR4(+) fibrocytes and the activation phenotypes CD45(+)Col1(+)p-SMAD2/3(+) and CD45(+)Col1(+)p-AKT(+). CONCLUSION: There was correlation between circulating fibrocyte subsets and asthma severity, and there was an increased number of activated/differentiated fibrocytes in circulating blood of asthmatic patients experiencing an exacerbation in the preceding 12 months. PMID- 26371838 TI - Allergy immunotherapy for allergic rhinitis effectively prevents asthma: Results from a large retrospective cohort study. AB - BACKGROUND: Allergic rhinitis (AR) is a main risk factor for the development of asthma. Two randomized open-label trials indicated that allergy immunotherapy (AIT) prevents the onset of asthma in patients with AR. However, these trials have methodological limitations, and it is unclear to what extent this experimental efficacy translates into clinical effectiveness. OBJECTIVES: We sought to investigate the effectiveness of AIT to prevent asthma in patients with AR. METHODS: Using routine health care data from German National Health Insurance beneficiaries, we identified a consecutive cohort of 118,754 patients with AR but without asthma who had not received AIT in 2005. These patients were stratified into one group starting AIT in 2006 and one group receiving no AIT in 2006. Both groups were observed regarding the risk of incident asthma in 2007 to 2012. Risk ratios (RRs) were calculated with generalized linear models by using a Poisson link function with robust error variance and adjustment for age, sex, health care use because of AR, and use of antihistamines. RESULTS: In a total of 2431 (2.0%) patients, AIT was started in 2006. Asthma was newly diagnosed from 2007-2012 in 1646 (1.4%) patients. The risk of incident asthma was significantly lower in patients exposed to AIT (RR, 0.60; 95% CI, 0.42-0.84) compared with patients receiving no AIT in 2006. Sensitivity analyses suggested significant preventive effects of subcutaneous immunotherapy (RR, 0.54; 95% CI, 0.38-0.84) and AIT including native (nonallergoid) allergens (RR, 0.22; 95% CI, 0.02-0.68). AIT for 3 or more years tended to have stronger preventive effects than AIT for less than 3 years. CONCLUSION: AIT effectively prevents asthma in patients with AR in a real-world setting. Confounding by indication cannot be excluded but would lead to an underestimation of the true preventive effects of AIT. PMID- 26371839 TI - Practice parameter for the diagnosis and management of primary immunodeficiency. AB - The American Academy of Allergy, Asthma & Immunology (AAAAI) and the American College of Allergy, Asthma & Immunology (ACAAI) have jointly accepted responsibility for establishing the "Practice parameter for the diagnosis and management of primary immunodeficiency." This is a complete and comprehensive document at the current time. The medical environment is a changing environment, and not all recommendations will be appropriate for all patients. Because this document incorporated the efforts of many participants, no single individual, including those who served on the Joint Task Force, is authorized to provide an official AAAAI or ACAAI interpretation of these practice parameters. Any request for information about or an interpretation of these practice parameters by the AAAAI or ACAAI should be directed to the Executive Offices of the AAAAI, the ACAAI, and the Joint Council of Allergy, Asthma & Immunology. These parameters are not designed for use by pharmaceutical companies in drug promotion. PMID- 26371840 TI - Exposure-response analyses for platinum salt-exposed workers and sensitization: A retrospective cohort study among newly exposed workers using routinely collected surveillance data. AB - BACKGROUND: Chloroplatinate salts are well-known respiratory sensitizing agents leading to work-related sensitization and allergies in the work environment. No quantitative exposure-response relation has been described for chloroplatinate salts. OBJECTIVE: We sought to evaluate the quantitative exposure-response relation between occupational chloroplatinate exposure and sensitization. METHODS: A retrospective cohort study was conducted using routinely collected health surveillance data and chloroplatinate exposure data. Workers who newly entered work between January 1, 2000, and December 31, 2010, were included, and the relation between measured chloroplatinate exposure and sensitization (as determined by skin prick test responses) was analyzed in more than 1000 refinery workers from 5 refineries for whom a total of more than 1700 personal exposure measurements were available. RESULTS: A clear exposure-response relation was observed, most strongly for more recent platinum salt exposure. Average or cumulative exposure over the follow-up period was less strongly associated with sensitization risk. The exposure-response relation was modified by smoking and atopy. CONCLUSIONS: Indications exist that recent exposure explains the risk of platinum salt sensitization most strongly. The precision of the estimate of the exposure-response relation derived from this data set appears superior to previous epidemiologic studies conducted on platinum salt sensitization and as a result, might have possible utility for the development of preventive strategies. PMID- 26371640 TI - Measurements of the Total and Differential Higgs Boson Production Cross Sections Combining the H->gammagamma and H->ZZ^{*}->4l Decay Channels at sqrt[s]=8 TeV with the ATLAS Detector. AB - Measurements of the total and differential cross sections of Higgs boson production are performed using 20.3 fb^{-1} of pp collisions produced by the Large Hadron Collider at a center-of-mass energy of sqrt[s]=8 TeV and recorded by the ATLAS detector. Cross sections are obtained from measured H->gammagamma and H->ZZ^{*}->4l event yields, which are combined accounting for detector efficiencies, fiducial acceptances, and branching fractions. Differential cross sections are reported as a function of Higgs boson transverse momentum, Higgs boson rapidity, number of jets in the event, and transverse momentum of the leading jet. The total production cross section is determined to be sigma_{pp >H}=33.0+/-5.3 (stat)+/-1.6 (syst) pb. The measurements are compared to state-of the-art predictions. PMID- 26371841 TI - Chronic cat allergen exposure induces a TH2 cell-dependent IgG4 response related to low sensitization. AB - BACKGROUND: In human subjects, allergen tolerance has been observed after high dose allergen exposure or after completed allergen immunotherapy, which is related to the accumulation of anti-inflammatory IgG4. However, the specific T cell response that leads to IgG4 induction during chronic allergen exposure remains poorly understood. OBJECTIVE: We sought to evaluate the relationship between cat allergen-specific T-cell frequency, cat allergen-specific IgE and IgG4 titers, and clinical status in adults with cat allergy with and without cat ownership and the cellular mechanism by which IgG4 is produced. METHODS: Fel d 1 , Fel d 4-, Fel d 7-, and Fel d 8-specific T-cell responses were characterized by CD154 expression after antigen stimulation. RESULTS: In allergic subjects without cat ownership, the frequency of cat allergen (Fel d 1 and Fel d 4)-specific TH2 (sTH2) cells correlates with higher IgE levels and is linked to asthma. Paradoxically, we observed that subjects with cat allergy and chronic cat exposure maintain a high frequency of sTH2 cells, which correlates with higher IgG4 levels and low sensitization. B cells from allergic, but not nonallergic subjects, are able to produce IgG4 after cognate interactions with sTH2 clones and Fel d 1 peptide or the Fel d 1 recombinant protein. CONCLUSION: These experiments suggest that (1) allergen-experienced B cells with the capacity to produce IgG4 are present in allergic subjects and (2) cat allergen exposure induces an IgG4 response in a TH2 cell-dependent manner. Thus IgG4 accumulation could be mediated by chronic activation of the TH2 response, which in turn drives desensitization. PMID- 26371842 TI - Neuropeptide signaling through neurokinin-1 and neurokinin-2 receptors augments antigen presentation by human dendritic cells. PMID- 26371846 TI - Characterization and evolution of the sediments of a Mediterranean coastal lagoon located next to a former mining area. AB - Coastal lagoons are ecosystems that are relatively enclosed water bodies under the influence of both the terrestrial and the marine environment, being vulnerable to human impacts. Human activities, such as mining extraction, are significant anthropogenic coastal stressors that can negatively affect ecosystems and communities. In light of the above, the objective of this research is to examine the influence of metal mining activities on the composition of sediments of a Mediterranean coastal lagoon, named Mar Menor. This paper presents a comprehensive characterization for grain size, mineralogy, geochemistry and organic matter of sediments of this coastal lagoon, investigating their variation along space and time. Sedimentation dynamics are ruling clearly the grain size predominant in each area of the Mar Menor coastal lagoon, determining the existence of entrainment, transport and sedimentation areas. For minerals, elements and organic matter, sedimentation dynamics are also determining their distribution. PMID- 26371845 TI - Informing Marine Spatial Planning (MSP) with numerical modelling: A case-study on shellfish aquaculture in Malpeque Bay (Eastern Canada). AB - A moratorium on further bivalve leasing was established in 1999-2000 in Prince Edward Island (Canada). Recently, a marine spatial planning process was initiated explore potential mussel culture expansion in Malpeque Bay. This study focuses on the effects of a projected expansion scenario on productivity of existing leases and available suspended food resources. The aim is to provide a robust scientific assessment using available datasets and three modelling approaches ranging in complexity: (1) a connectivity analysis among culture areas; (2) a scenario analysis of organic seston dynamics based on a simplified biogeochemical model; and (3) a scenario analysis of phytoplankton dynamics based on an ecosystem model. These complementary approaches suggest (1) new leases can affect existing culture both through direct connectivity and through bay-scale effects driven by the overall increase in mussel biomass, and (2) a net reduction of phytoplankton within the bounds of its natural variation in the area. PMID- 26371844 TI - Cesarean section and disease associated with immune function. AB - BACKGROUND: Earlier studies have shown that delivery by cesarean section (CS) is associated with an increased risk of disease associated with immune function in the offspring, but these studies have generally not discriminated between the effect of acute and elective CS. OBJECTIVE: We sought to further explore these associations using discrimination between the effects of acute versus elective CS. METHODS: We performed a population- and national register-based cohort study including all children born in Denmark from January 1997 through December 2012. Hazard ratios for diseases associated with immune function in children delivered by acute and elective CS with vaginal delivery as the reference were calculated by using Cox regression. All analyses were adjusted for gestational age, sex, birth weight, maternal age, maternal smoking during pregnancy, and complications during pregnancy (preeclampsia, eclampsia, hemorrhage, and hyperemesis). RESULTS: A total of 750,569 children aged 0 to 14 years were included. Children delivered by both acute and elective CS had an increased risk of asthma, laryngitis, and gastroenteritis. Children delivered by acute CS had an increased risk of ulcerative colitis and celiac disease, whereas children delivered by elective CS had an increased risk of lower respiratory tract infection and juvenile idiopathic arthritis. The effect of elective CS was higher than the effect of acute CS on the risk of asthma. CONCLUSION: Children delivered by CS are at increased risk of disease associated with immune function. The effect is mainly on diseases involving the mucosal immune system. PMID- 26371843 TI - Sublingual grass and ragweed immunotherapy: Clinical considerations-a PRACTALL consensus report. AB - Sublingual allergen immunotherapy provides a new option for patients with allergic rhinitis in the United States. The efficacy of these sublingual immunotherapy tablets in the treatment of allergic rhinitis has been firmly established in large multicenter clinical trials. In addition, the clinical benefits of sublingual immunotherapy might persist after treatment is discontinued. Local reactions, such as gastrointestinal or oropharyngeal symptoms, are common. However, severe anaphylaxis is rare, and therefore the immunotherapy tablets can be administered at home. Sublingual immunotherapy for allergic rhinitis has been used successfully for years in Europe, and these products might be appropriate for patients who do not do well with standard drug therapy or for those who prefer a disease-modifying approach. PMID- 26371848 TI - Environmental risk assessments and spatial variations of polycyclic aromatic hydrocarbons in surface sediments in Yangtze River Estuary, China. AB - In this study, based on sampling data from 30 sites in August 2010, the environmental risks associated with 16 priority PAHs were estimated in surface sediments from the Yangtze River Estuary (YRE). The results indicated that the toxic equivalent quantities of the benzo[a]pyrene (TEQBap) from 30 sites were in the range of 1.93-75.88ngg(-1), and the low-molecular-weight PAHs were the dominated species with higher potential toxicity. The results of the Incremental Lifetime Cancer Risk (ILCR) model indicated that the ILCR values of dermal contact were higher than 10(-6) in the northeast region, suggesting that there were significant potential carcinogenic health risks for fishermen exposure to sedimentary PAHs via dermal contact in these areas. RQ values of PAHs indicated the various distributions of ecological risk levels in the study area. These variations might be caused by the natural and anthropogenic inputs and currents in the YRE. PMID- 26371847 TI - Inputs of anthropogenic nitrogen influence isotopic composition and trophic structure in SE Australian estuaries. AB - Urban development in coastal settings has increased the input of nitrogen into estuaries globally, in many cases changing the composition of estuarine ecosystems. By focussing on three adjacent estuaries with a gradient of anthropogenic N loadings, we used stable isotopes of N and C to test for changes due to increased anthropogenic N input on the structure of some key trophic linkages in estuaries. We found a consistent enrichment in delta(15)N corresponding to increased anthropogenic N at the three ecosystem levels studied: fine benthic organic matter, grazing invertebrate, and planktivorous fish. The degree of enrichment in delta(15)N between fine benthic organic matter and the grapsid crab Parasesarma erythrodactyla was identical across the three sites. The glassfish Ambassis jacksoniensis showed lower levels of enrichment compared to basal food sources at the higher N-loaded sites, suggesting a possible effect of anthropogenic N in decreasing food-chain length in these estuaries. PMID- 26371851 TI - Acetic acid chromoendoscopy for the diagnosis of early neoplasia and specialized intestinal metaplasia in Barrett's esophagus: a meta-analysis. AB - BACKGROUND AND AIMS: Barrett's esophagus (BE) surveillance with random biopsies is time-consuming, invasive, and can lead to sampling error. Acetic acid chromoendoscopy (AAC) with targeted biopsies has been proposed as an effective alternative. The aim of this study was to assess the diagnostic accuracy of AAC for the detection of early neoplasia (high-grade dysplasia [HGD] or early cancer [EC]) and specialized intestinal metaplasia (SIM) in patients with BE. METHODS: We performed a meta-analysis of all primary studies that compared AAC-based diagnoses (index test) with histopathology as the reference standard. The data were extracted on a per-patient, per-area, and per-procedure basis whenever available. RESULTS: Thirteen prospective studies met the inclusion criteria. For the diagnosis of HGD/EC, the pooled sensitivity, specificity, positive likelihood ratio (LR+), and negative likelihood ratio (LR-) for all included studies (9 studies, 1379 patients) were 0.92 (95% confidence interval [CI], 0.83-0.97), 0.96 (95% CI, 0.85-0.99), 25.0 (95% CI, 5.9-105.3), and 0.08 (95% CI, 0.04-0.18), respectively. Results were not significantly different when considering only studies with a per-patient analysis. For the characterization of SIM, the pooled sensitivity, specificity, LR+, and LR- for all the included studies (8 studies, 516 patients) were 0.96 (95% CI, 0.83-0.99), 0.69 (95% CI, 0.54-0.81), 3.0 (95% CI, 2.0-4.7), and 0.06 (95% CI, 0.01-0.26), respectively. No significant sources of heterogeneity were identified on subgroup analysis. CONCLUSION: AAC has an overall high diagnostic accuracy for detecting HGD/EC in patients with BE. For SIM characterization, AAC sensitivity is very high but has poor specificity, suggesting that histological confirmation is necessary when AAC is positive. PMID- 26371849 TI - Effects of the antioxidants Trolox, Tiron and Tempol on neutrophil extracellular trap formation. AB - Neutrophils can entrap and kill pathogens by releasing of neutrophil extracellular traps (NETs), in addition to their routine functions such as phagocytosis and degranulation. NETs consist of a DNA backbone supplemented by multiple bactericidal proteins from the nucleus, the cytoplasm and the granules. Neutrophils release NETs after their activation by a number of physiological and pharmacological stimuli. In addition to the antimicrobial function, NETs are involved in the pathogenesis of various autoimmune and inflammatory diseases. Since NET formation predominantly depends on the generation of reactive oxygen species (ROS), all substances that are capable of scavenging ROS or inhibiting the enzymes responsible for their synthesis should prevent ROS-associated NET release. The aim of this study was to test substances with an antioxidant activity, such as Trolox, Tiron, and Tempol, for their capacity to inhibit NET formation by primary human neutrophils in vitro. We revealed for the first time an inhibitory effect of Trolox on ROS-dependent NET release. We also established a suppressive effect of Tempol on NET formation that manifested itself in a wide range of concentrations. In this study, no inhibitory influence of Tiron on NET release was revealed. All tested substances exerted a significant dose-dependent antioxidative effect on ROS generation induced by phorbol 12-myristate 13-acetate (PMA). We suggest that the antioxidants Trolox and Tempol should be recommended for treating autoimmune and inflammatory diseases that implicate ROS-dependent NET release. PMID- 26371850 TI - Performance characteristics of unsedated ultrathin video endoscopy in the assessment of the upper GI tract: systematic review and meta-analysis. AB - BACKGROUND AND AIMS: Reports on the performance of unsedated ultrathin endoscopy via the transnasal (uTNE) and transoral (uTOE) routes are conflicting. We aimed to estimate the technical success rate, patient preference, and acceptability of uTNE and uTOE alone and in comparison with conventional EGD (cEGD; with or without sedation). METHODS: A systematic review and meta-analysis was performed on all primary studies reporting the outcomes of interest. Electronic databases (Cochrane library, MEDLINE, EMBASE) were searched on February 1, 2014. RESULTS: Thirty-four studies met the inclusion criteria with 6659 patients in total. The pooled technical success rate was 94.0% for uTNE (95% confidence interval [CI], 91.6-95.8; 30 studies) and 97.8% for uTOE (95% CI, 95.6-98.9; 16 studies). The difference in proportion of success for uTNE compared with cEGD was -2.0% (95% CI, -4.0 to -1.0; 18 studies), but that difference was not significant when uTNE < 5.9 mm in diameter was used (-1.0%; 95% CI, -3.0 to .0; 9 studies). There was no significant difference in success rate between uTOE and cEGD (.0%; 95% CI, 1.0 to 2.0; 10 studies). The pooled difference in proportion of patients who preferred uTNE over cEGD was 63.0% (95% CI, 49.0-76.0; 10 studies), whereas preference for uTOE versus cEGD was not significantly different (38.0%; 95% CI, 4.0 to 80.0; 2 studies). Acceptability was high for both uTNE (85.2%; 95% CI, 79.1-89.9; 16 studies) and uTOE (88.7%; 95% CI, 82.4-92.9; 10 studies). CONCLUSIONS: Technical success rate for uTNE < 5.9 mm is equivalent to cEGD. uTNE has high patient acceptability, with better patient preference, and therefore could be a useful alternative to cEGD for screening purposes. uTOE had a similar technical success rate but an equivocal preference to cEGD. PMID- 26371852 TI - Small ruminant lentivirus infections and diseases. AB - Small ruminant lentiviruses include viruses with diverse genotypes that frequently cross the species barrier between sheep and goats and that display a great genetic variability. These characteristics stress the need to consider the whole host range and to perform local surveillance of the viruses to opt for optimum diagnostic tests, in order to establish control programmes. In the absence of effective vaccines, a comprehensive knowledge of the epidemiology of these infections is of major importance to limit their spread. This article intends to cover these aspects and to summarise information related to characteristics of the viruses, pathogenesis of the infection and description of the various syndromes produced, as well as the diagnostic tools available, the mechanisms involved in transmission of the pathogens and, finally, the control strategies that have been designed until now, with remarks on the drawbacks and the advantages of each one. We conclude that there are many variables influencing the expected cost and benefits of control programs that must be evaluated, in order to put into practice measures that might lead to control of these infections. PMID- 26371853 TI - Doxycycline as an inhibitor of p-glycoprotein in the alpaca for the purpose of maintaining avermectins in the CNS during treatment for parelaphostrongylosis. AB - Meningeal worms (Parelaphostrongylus tenuis) are a common malady of alpacas, often refractory to conventional treatments. Ivermectin is a very effective anthelmintic used against a variety of parasites but this drug is not consistently effective against alpaca meningeal worms once the parasite has gained access to the CNS, even if used in a protracted treatment protocol. Ivermectin is not effective against clinical cases of P. tenuis, raising the possibility that the drug is not sustained at therapeutic concentrations in the central nervous system (CNS). A specific protein (designated as p-glycoprotein (PGP)) effluxes ivermectin from the brain at the blood-brain barrier, thus hampering the maintenance of therapeutic concentrations of the drug in the CNS. Minocycline is a synthetic tetracycline antibiotic with an excellent safety profile in all animals tested to date. Minocycline has three unique characteristics that could be useful for treating meningeal worms in conjunction with ivermectin. First, minocycline is an inhibitor of PGP at the blood-brain barrier and this inhibition could maintain effective concentrations of ivermectin in the brain and meninges. Second, minocycline protects neurons in vivo through a number of different mechanisms and this neuroprotection could alleviate the potential untoward neurologic effects of meningeal worms. Third, minocycline is a highly lipid-soluble drug, thus facilitating efficient brain penetration. We thus hypothesized that minocycline will maintain ivermectin, or a related avermectin approved in ruminants (abamectin, doramectin, or eprinomectin), in the alpaca CNS. To test this hypothesis, we cloned the gene encoding the alpaca PGP, expressed the alpaca PGP in a heterologous expression system involving MDCK cells, and measured the ability of minocycline to inhibit the efflux of avermectins from the MDCK cells; doxycycline was used as a putative negative control (based on studies in other species). Our in vitro studies surprisingly revealed that doxycycline was effective at inhibiting the efflux of ivermectin and doramectin (minocycline had no effect). These two avermectins, in combination with doxycycline, should be considered when treating meningeal worms in alpacas. PMID- 26371854 TI - Biomechanical response to ankle-foot orthosis stiffness during running. AB - BACKGROUND: The Intrepid Dynamic Exoskeletal Orthosis (IDEO) is an ankle-foot orthosis developed to address the high rates of delayed amputation in the military. Its use has enabled many wounded Service Members to run again. During running, stiffness is thought to influence an orthosis' energy storage and return mechanical properties. This study examined the effect of orthosis stiffness on running biomechanics in patients with lower limb impairments who had undergone unilateral limb salvage. METHODS: Ten patients with lower limb impairments underwent gait analysis at a self-selected running velocity. 1. Nominal (clinically-prescribed), 2. Stiff (20% stiffer than nominal), and 3. Compliant (20% less stiff than nominal) ankle-foot orthosis stiffnesses were tested. FINDINGS: Ankle joint stiffness was greatest in the stiffest strut and lowest in the compliant strut, however ankle mechanical work remained unchanged. Speed, stride length, cycle time, joint angles, moments, powers, and ground reaction forces were not significantly different among stiffness conditions. Ankle joint kinematics and ankle, knee and hip kinetics were different between limbs. Ankle power, in particular, was lower in the injured limb. INTERPRETATION: Ankle-foot orthosis stiffness affected ankle joint stiffness but did not influence other biomechanical parameters of running in individuals with unilateral limb salvage. Foot strike asymmetries may have influenced the kinetics of running. Therefore, a range of stiffness may be clinically appropriate when prescribing ankle-foot orthoses for active individuals with limb salvage. PMID- 26371855 TI - Biomechanical gait characteristics of naturally occurring unsuccessful foot clearance during swing in individuals with chronic stroke. AB - BACKGROUND: Altered gait mechanics are common following stroke and may increase the risk of falls. Paretic gait impairments have been previously compared to the non-paretic limb or control participants. Unfortunately, the biomechanical parameters underlying instances of naturally occurring unsuccessful foot clearance (trips) have yet to be examined in individuals with chronic stroke. METHODS: Gait data from 26 participants with chronic stroke were obtained on a dual-belt instrumented treadmill. Instances of successful and unsuccessful foot swing were identified. Temporal, kinematic, and kinetic measures of the paretic limb occurring during late stance, toe-off, and swing were compared between trip and non-trip steps using paired samples t-tests. An alpha = 0.004 was used to adjust for multiple comparisons. FINDINGS: In the paretic limb, the ankle angle at toe off (P = 0.003; d = 0.64), knee flexion velocity at toe off (P < 0.001; d = 0.73), and peak knee extension moment during terminal stance (P < 0.001; d = 0.74) were significantly different between trips and non-trip steps. During trip steps, ankle plantarflexion at toe-off was 1.0 degrees greater, knee flexion velocity was reduced by 17.6 degrees /sec, and peak knee extension moment was increased by 0.011 Nm/kg . m compared to non-trip steps. INTERPRETATION: It appears to take only minor changes in the movement of the paretic limb to result in a trip in individuals with chronic stroke. Although small, the multi-joint biomechanical changes occurring in the paretic limb during unsuccessful foot clearance result in a functionally longer limb. Thus, interventions targeting multiple joints in the paretic limb may be needed to reduce the risk of trips following stroke. PMID- 26371856 TI - Milk of calcium pericardial effusion. PMID- 26371858 TI - The anacardic 6-pentadecyl salicylic acid induces macrophage activation via the phosphorylation of ERK1/2, JNK, P38 kinases and NF-kappaB. AB - Amphipterygium adstringens is a plant traditionally used to treat gingivitis, gastric ulcer and even gastric cancer but the mechanism involved in the regulation of the immune response is not elucidated yet. The 6 pentadecylsalicylic acid (6SA) is the main anacardic acid found in A. adstringens. In order to evaluate the immune-modulatory abilities of 6SA, we used mouse splenocytes and determined the phosphorylation of the transcription factor NF-kappaB and MAP kinases ERK1/2, JNK and p38 in helper and cytotoxic T cells, natural killer (NK) cells and F4/80(+) macrophages. Treatment with 6SA was not cytotoxic as measured by both trypan blue exclusion and tetrazolium salts (MTT) tests. Additionally, 6SA did not alter the proportion of helper and cytotoxic T lymphocytes, NK cells or macrophages. Moreover, 6SA treatment significantly increased the phosphorylation of ERK1/2, JNK, P38 and NF-kappaB mainly in macrophages. In this cells (peritoneal macrophages), treatment with 6SA increased the secretion of nitric oxide (NO), interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha and decreased the secretion of IL-4 and IL-10 depending on MAPK and NF-kappaB phosphorylation. In addition, 6SA increased the migration and phagocytic activity of macrophages also depending on the phosphorylation of different kinases. These data suggest that 6SA induces the classical activation pathway in macrophages via the phosphorylation of MAP kinases and NF-kappaB thus activating the adaptive immune system. PMID- 26371857 TI - Anti-inflammatory effect of desoxo-narchinol-A isolated from Nardostachys jatamansi against lipopolysaccharide. AB - We previously reported that Nardostachys jatamansi (NJ) exhibits anti inflammatory activity against lipopolysaccharide (LPS). However, the active compound in NJ is unknown. Therefore, here, we examined the effects of desoxo narchinol-A (DN) isolated from NJ against LPS-induced inflammation. To demonstrate the anti-inflammatory effect of DN against LPS, we used two models; murine endotoxin shock model for in vivo model, and peritoneal macrophage responses for in vitro. In endotoxin shock model, DN was administrated intraperitoneally 1h before LPS challenge, then we evaluated mice survival rates and organ damages. Pretreatment with DN (0.05mg/kg, 0.1mg/kg, or 0.5mg/kg) dramatically reduced mortality in a murine LPS-induced endotoxin shock model. Furthermore, DN inhibited tissue injury and production of pro-inflammatory cytokines, such as interleukin (IL)-1beta, IL-6, and tumor necrosis factor alpha (TNF-alpha), in the liver and lung. In in vitro macrophage model, we examined the inflammatory mediators and regulatory mechanisms such as mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-kappaB). DN inhibited the production of inflammatory mediators, such as inducible nitric oxide synthase (iNOS) and its derivative nitric oxide (NO), cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), IL-1beta, IL-6 and TNF-alpha and H3 protein acetylation in murine peritoneal macrophages. DN also inhibited p38 activation, but not extracellular signal-regulated kinase (ERK), c-jun NH2-terminal kinase (JNK), and NF-kappaB. These results suggest that DN from NJ exhibits protective effects against LPS-induced endotoxin shock and inflammation through p38 deactivation. PMID- 26371859 TI - Geniposide alleviates inflammation by suppressing MeCP2 in mice with carbon tetrachloride-induced acute liver injury and LPS-treated THP-1 cells. AB - Geniposide (GP), an iridoid glucoside extracted from Gardenia jasminoides Ellis fruits, has been used as a herbal medicine to treat liver and gall bladder disorders for many years. However the mechanism of anti-inflammatory is largely unknown. In this study, GP significantly attenuated inflammation in acute liver injury (ALI) mice model and in lipopolysaccharide (LPS)-induced THP-1 cells. It was demonstrated that GP obviously decreased the expression of Methyl-CpG binding protein 2 (MeCP2) in vivo and in vitro. Knockdown of MeCP2 with siRNA suppressed the expressions of IL-6 and TNF-alpha, while over-expression of MeCP2 had a proinflammatory effect on the expression of IL-6 and TNF-alpha in LPS-induced THP 1 cells. Mechanistically, it was indicated that GP had anti-inflammatory effects at least in part, through suppressing MeCP2. Interestingly, GP could attenuate expressions of Sonic hedgehog (Shh) and GLIS family zinc finger 1 (GLIS1) but increase Ptched1 (PTCH1) expression. Similar findings were also demonstrated at the protein level by siRNA MeCP2. Furthermore, over-expression of MeCP2 obviously increased Shh and GLIS1 expressions but reduced PTCH1 expression. Taken together, GP may serve as an effective modulator of MeCP2-hedgehog pathway (Hh)-axis during the pathogenesis of inflammation. Our findings shed light on the potential therapeutic feature of GP in recovering inflammatory diseases. PMID- 26371860 TI - Activation of NRF2 pathway in spleen, thymus as well as peripheral blood mononuclear cells by acute arsenic exposure in mice. AB - Arsenic has already been demonstrated to activate the nuclear factor erythroid 2 related factor 2 (NRF2) in many different organs and cell lines. The present study tried to explore the expression of NRF2 pathway by acute arsenic exposure in immune system in vivo. Our results showed that treatment with arsenic (sodium arsenite, 5, 10 and 20mg/kg, intra-gastrically) increased the expression of NRF2 and its downstream targets heme oxygenase-1 (HO-1), glutathione-S-transferase (GST), glutamate-cysteine ligase (GCL) and glutathione reductase (GR) consistently in spleen, thymus, as well as peripheral blood mononuclear cells (PBMCs), as early as treatment from 6h. Arsenic was also detected to up-regulate the mRNA levels of Hmox1, NAD(P)H: quinine oxidoreductase 1 (Nqo1), Gclc and Gclm in spleen and thymus. Besides, we detected the enhancement of Kelch-like ECH associated protein (KEAP1) expression in these immune organs and immunocytes. What's more, our results also found the imbalanced oxidative redox status under the circumstances that arsenic activated NRF2 pathway, reflected by the generation of lipid peroxidation, as well as the reduction of antioxidative capacities in both spleen and thymus. Taken together, our results here strongly suggested the expression and activation of NRF2 pathway by acute arsenic exposure in immune system in vivo. Further studies are being investigated to explore the possible roles and functions of NRF2 pathway stimulation in the regulation of immune responses of this metalloid. PMID- 26371861 TI - Hypothemycin inhibits tumor necrosis factor-alpha production by tristetraprolin dependent down-regulation of mRNA stability in lipopolysaccharide-stimulated macrophages. AB - Hypothemycin, a resorcylic acid lactone polyketide, has been shown to inhibit oncogenic ras-transformation and T cell activation. In the present study, we investigated the effect of hypothemycin on tumor necrosis factor-alpha (TNF alpha) production in macrophages and the molecular mechanisms involved in this effect. Hypothemycin potently suppressed the TNF-alpha production without affecting nitric oxide production in lipopolysaccharide (LPS)-stimulated macrophages. However, hypothemycin had no effect on the activity of TNF-alpha converting enzyme, a key enzyme for converting membrane-bound pro-TNF-alpha into soluble TNF-alpha. Further study demonstrated that the stability of TNF-alpha mRNA was decreased by hypothemycin treatment. In addition, hypothemycin suppressed LPS-induced phosphorylation of p38 MAPK and ERK. Moreover, knockdown of tristetraprolin (TTP), which is an important trans-acting regulator of TNF alpha mRNA stability and downstream target of p38 MAPK and ERK, reversed hypothemycin-mediated inhibition of TNF-alpha mRNA expression. Collectively, our results suggest that hypothemycin suppresses TNF-alpha production by TTP dependent destabilization of TNF-alpha mRNA and this is mediated, at least in part, by blocking the activation of p38 MAPK and ERK. PMID- 26371862 TI - Stretching of collapsed polymers causes an enhanced dissipative response of PNIPAM brushes near their LCST. AB - Poly(N-isopropyl acrylamide) (PNIPAM) is a stimulus-responsive polymer that can switch in water from an expanded state below the lower critical solution temperature (LCST) of 32 degrees C to a globular state above the LCST. It was recently shown that, as a consequence of this conformational transition, the interfacial and (tribo-)mechanical properties of polymeric systems composed of PNIPAM can be switched between two states. Here we show that the tribo-mechanical properties of a particular type of PNIPAM system, which is the PNIPAM brush, do not just change between two states, but instead evolve continuously and non monotonically upon increasing/decreasing temperature. To do so, we present atomic force microscopy experiments in which we measure the adhesion hysteresis and the friction upon bringing a gold colloid in relative motion with PNIPAM brushes at temperatures around the LCST. Both the friction and the adhesion hysteresis display a pronounced maximum exactly at the LCST. The force vs. distance data captured at these temperatures show a long-ranged adhesive interaction upon moving the colloid away from the original point of contact, which indicates that during this retraction the partly collapsed polymers in the brush become strongly stretched. PMID- 26371863 TI - Response to the Letter to the Editor regarding "A comparison of two myringoplasty techniques in Nepalese children: A prospective randomized trial" by Tripathi et al. [Int. J. Pediatr. Otorhinolaryngol. 2015 (79) (9) 1556-1560]. PMID- 26371864 TI - Administration of pneumococcal vaccine in Hajj. PMID- 26371865 TI - Reply to Penelope A. McNulty and Emma F. Hodson-Tole. PMID- 26371866 TI - Social deprivation, population dependency ratio and an extended hospital episode Insights from acute medicine. AB - BACKGROUND: Patients from deprived backgrounds have a higher in-patient mortality following an emergency medical admission; this study aimed to investigate the extent to which Deprivation status and the population Dependency Ratio influenced extended hospital episodes. METHODS: All Emergency Medical admissions (75,018 episodes of 41,728 patients) over 12 years (2002-2013) categorized by quintile of Deprivation Index and Population Dependency Rates (proportion of non working/working) were evaluated against length of stay (LOS). Patients with an Extended LOS (ELOS), >30 days, were investigated, by Deprivation status, Illness Severity and Co-morbidity status. Univariate and multi-variable risk estimates (Odds Rates or Incidence Rate Ratios) were calculated, using truncated Poisson regression. RESULTS: Hospital episodes with ELOS had a frequency of 11.5%; their median LOS (IQR) was 55.0 (38.8, 97.6) days utilizing 57.6% of all bed days by all 75,018 emergency medical admissions. The Deprivation Index independently predicted the rate of such ELOS admissions; these increased approximately five fold (rate/1000 population) over the Deprivation Quintiles with model adjusted predicted admission rates of for Q1 0.93 (95% CI: 0.86, 0.99), Q22.63 (95% CI: 2.55, 2.71), Q3 3.84 (95% CI: 3.77, 3.91), Q4 3.42 (95% CI: 3.37, 3.48) and Q5 4.38 (95% CI: 4.22, 4.54). Similarly the Population Dependency Ratio Quintiles (dependent to working structure of the population by small area units) independently predicted extended LOS admissions. CONCLUSION: The admission of patients with an ELOS is strongly influenced by the Deprivation status and the population Dependency Ratio of the catchment area. These factors interact, with both high deprivation and Dependency cohorts having a major influence on the numbers of emergency medical admission patients with an extended hospital episode. PMID- 26371867 TI - A Comprehensive Analysis in Terms of Molecule-Intrinsic, Quasi-Atomic Orbitals. III. The Covalent Bonding Structure of Urea. AB - The analysis of molecular electron density matrices in terms of quasi-atomic orbitals, which was developed in previous investigations, is quantitatively exemplified by a detailed application to the urea molecule. The analysis is found to identify strong and weak covalent bonding interactions as well as intramolecular charge transfers. It yields a qualitative as well as quantitative ab initio description of the bonding structure of this molecule, which raises questions regarding some traditional rationalizations. PMID- 26371869 TI - Measurement of clavicular length and shortening after a midshaft clavicular fracture: Spatial digitization versus planar roentgen photogrammetry. AB - PURPOSE: Clavicular shortening after fracture is deemed prognostic for clinical outcome and is therefore generally assessed on radiographs. It is used for clinical decision making regarding operative or non-operative treatment in the first 2weeks after trauma, although the reliability and accuracy of the measurements are unclear. This study aimed to assess the reliability of roentgen photogrammetry (2D) of clavicular length and shortening, and to compare these with 3D-spatial digitization measurements, obtained with an electromagnetic recording system (Flock of Birds). PATIENTS AND METHODS: Thirty-two participants with a consolidated non-operatively treated two or multi-fragmented dislocated midshaft clavicular fracture were analysed. Two observers measured clavicular lengths and absolute and proportional clavicular shortening on radiographs taken before and after fracture consolidation. The clavicular lengths were also measured with spatial digitization. Inter-observer agreement on the radiographic measurements was assessed using the Intraclass Correlation Coefficient (ICC). Agreement between the radiographic and spatial digitization measurements was assessed using a Bland-Altman plot. RESULTS: The inter-observer agreement on clavicular length, and absolute and proportional shortening on trauma radiographs was almost perfect (ICC>0.90), but moderate for absolute shortening after consolidation (ICC=0.45). The Bland-Altman plot compared measurements of length on AP panorama radiographs with spatial digitization and showed that planar roentgen photogrammetry resulted in up to 37mm longer and 34mm shorter measurements than spatial digitization. CONCLUSION: Measurements of clavicular length on radiographs are highly reliable between observers, but may not reflect the actual length and shortening of the clavicle when compared to length measurements with spatial digitization. We recommend to use proportional shortening when measuring clavicular length or shortening on radiographs for clinical decision making. PMID- 26371871 TI - Glucocorticoids retard skeletal muscle development and myoblast protein synthesis through a mechanistic target of rapamycin (mTOR)-signaling pathway in broilers (Gallus gallus domesticus). AB - Glucocorticoids exert a well-known catabolic protein action on skeletal muscle. The mechanistic target of rapamycin (mTOR) signaling pathway acts as a central regulator of protein metabolism. Whether glucocorticoids regulate protein synthesis through the mTOR pathway in skeletal muscle of chickens remains unknown. This study was performed to characterize the effect of glucocorticoids on the mTOR pathway in skeletal muscle development in chickens, and on protein synthesis in cultured embryonic myoblasts. Male 29-d-old chickens were given a dexamethasone injection (2 mg/kg) twice per day for 4 d (n = 16). Chicken embryonic myoblasts were exposed to dexamethasone for 24 h (100 umol/L, n = 4 cultures). The interaction between dexamethasone and leucine was also investigated. ANOVA and Duncan's multiple test were used to analyze the effects of the dexamethasone and leucine treatments. The results showed that dexamethasone decreased body weight gain, body weight, and feed efficiency. Protein synthesis was inhibited by in vitro dexamethasone exposure. Phosphorylation of mTOR and ribosomal protein S6 protein kinase (p70S6K) were inhibited by dexamethasone, suggesting the mTOR pathway may be involved in dexamethasone-regulated muscle protein synthesis. Phosphorylation of AMP activated protein kinase (AMPK) was not altered in vitro but was reduced in vivo by dexamethasone. These results imply that the mTOR and AMPK pathways are both involved in retarding muscle development and protein synthesis by glucocorticoids, but the mTOR pathway is a critical point linking glucocorticoid and protein synthesis. Leucine, at least partially, inhibited the effects of dexamethasone on protein synthesis via the mTOR pathway. PMID- 26371872 TI - Present and future treatment options for primary CNS lymphoma. AB - INTRODUCTION: Primary Central Nervous System (CNS) lymphomas are a rare group of malignancies with peculiar clinical and biologic features, aggressive course, and unsatisfactory outcome in contrast with other aggressive lymphomas. Despite a high chemo- and radiosensitivity, remissions are frequently short lasting, mainly because the blood-brain barrier limits the access of many drugs to the CNS, preventing a homogeneous treatment of all CNS tissues. Moreover, survivor patients are at high risk of developing severe treatment-related toxicity, mainly disabling neurotoxicity for elderly ones, raising the question of whether to intensify therapy to improve the cure rate or to downgrade treatment to reduce side effects. Although prognosis remains poor, it has significantly improved over the past two decades as a result of better treatment strategies with a curative aim. AREAS COVERED: The purpose of this review is to focus on either the actual pharmaco-therapeutic knowledge or the predictable future developments for the immunocompetent population (the vast majority of patients today). The most important published reports on these fields are presented. EXPERT OPINION: Actual front-line therapy consists of high-dose-methotrexate-based polichemotherapy, mostly in combination with high-dose cytarabine and/or alkylating agents. The use of high-dose chemotherapy supported by autologous stem-cell transplantation is increased; with some pros and cons, this strategy appears in controlling microscopic disease. Management of intraocular and meningeal lymphomas is controversial considering their peculiar characteristics that need to be specifically addressed. Finally, management of elderly patients and of relapsed disease is addressed. PMID- 26371870 TI - GnT1IP-L specifically inhibits MGAT1 in the Golgi via its luminal domain. AB - Mouse GnT1IP-L, and membrane-bound GnT1IP-S (MGAT4D) expressed in cultured cells inhibit MGAT1, the N-acetylglucosaminyltransferase that initiates the synthesis of hybrid and complex N-glycans. However, it is not known where in the secretory pathway GnT1IP-L inhibits MGAT1, nor whether GnT1IP-L inhibits other N-glycan branching N-acetylglucosaminyltransferases of the medial Golgi. We show here that the luminal domain of GnT1IP-L contains its inhibitory activity. Retention of GnT1IP-L in the endoplasmic reticulum (ER) via the N-terminal region of human invariant chain p33, with or without C-terminal KDEL, markedly reduced inhibitory activity. Dynamic fluorescent resonance energy transfer (FRET) and bimolecular fluorescence complementation (BiFC) assays revealed homomeric interactions for GnT1IP-L in the ER, and heteromeric interactions with MGAT1 in the Golgi. GnT1IP L did not generate a FRET signal with MGAT2, MGAT3, MGAT4B or MGAT5 medial Golgi GlcNAc-tranferases. GnT1IP/Mgat4d transcripts are expressed predominantly in spermatocytes and spermatids in mouse, and are reduced in men with impaired spermatogenesis. PMID- 26371873 TI - Beyond Directed ortho Metalation: Ruthenium-Catalyzed Amide-Directed CAr-OMe Activation/Cross-Coupling Reaction of Naphthamides with Aryl Boronates. AB - A new and general synthetic methodology for the construction of biaryl, heterobiaryl, and polyaryl molecules by the ruthenium-catalyzed cross-coupling of ortho-methoxy naphthamides with aryl boroneopentylates is described. The isomeric 1-MeO-2-naphthamides and 2-MeO-1-naphthamides furnish an expansive series of arylated naphthamides in excellent yields. Competition experiments showed the higher reactivity of 1-MeO-2-naphthamide over 2-MeO-benzamide. Orthogonality between the C-O activation/cross-coupling and the Suzuki-Miyaura reactions was established. The method provides naphthalenes which are difficult to prepare by directed ortho metalation. PMID- 26371874 TI - Yellow Fever 17DD Vaccine Virus Infection Causes Detectable Changes in Chicken Embryos. AB - The yellow fever (YF) 17D vaccine is one of the most effective human vaccines ever created. The YF vaccine has been produced since 1937 in embryonated chicken eggs inoculated with the YF 17D virus. Yet, little information is available about the infection mechanism of YF 17DD virus in this biological model. To better understand this mechanism, we infected embryos of Gallus gallus domesticus and analyzed their histopathology after 72 hours of YF infection. Some embryos showed few apoptotic bodies in infected tissues, suggesting mild focal infection processes. Confocal and super-resolution microscopic analysis allowed us to identify as targets of viral infection: skeletal muscle cells, cardiomyocytes, nervous system cells, renal tubular epithelium, lung parenchyma, and fibroblasts associated with connective tissue in the perichondrium and dermis. The virus replication was heaviest in muscle tissues. In all of these specimens, RT-PCR methods confirmed the presence of replicative intermediate and genomic YF RNA. This clearer characterization of cell targets in chicken embryos paves the way for future development of a new YF vaccine based on a new cell culture system. PMID- 26371875 TI - Recessive TBC1D24 Mutations Are Frequent in Moroccan Non-Syndromic Hearing Loss Pedigrees. AB - Mutations in the TBC1D24 gene are responsible for four neurological presentations: infantile epileptic encephalopathy, infantile myoclonic epilepsy, DOORS (deafness, onychodystrophy, osteodystrophy, mental retardation and seizures) and NSHL (non-syndromic hearing loss). For the latter, two recessive (DFNB86) and one dominant (DFNA65) mutations have so far been identified in consanguineous Pakistani and European/Chinese families, respectively. Here we report the results of a genetic study performed on a large Moroccan cohort of deaf patients that identified three families with compound heterozygote mutations in TBC1D24. Four novel mutations were identified, among which, one c.641G>A (p.Arg214His) was present in the three families, and has a frequency of 2% in control Moroccan population with normal hearing, suggesting that it acts as an hypomorphic variant leading to restricted deafness when combined with another recessive severe mutation. Altogether, our results show that mutations in TBC1D24 gene are a frequent cause (>2%) of NSHL in Morocco, and that due to its possible compound heterozygote recessive transmission, this gene should be further considered and screened in other deaf cohorts. PMID- 26371876 TI - Simulating Deforestation in Minas Gerais, Brazil, under Changing Government Policies and Socioeconomic Conditions. AB - Agricultural expansion is causing deforestation in Minas Gerais, Brazil, converting savanna and tropical dry forest to farmland, and in 2012, Brazil's Forest Code was revised with the government reducing deforestation restrictions. Understanding the effects of policy change on rates and locations of natural ecosystem loss is imperative. In this paper, deforestation in Minas Gerais was simulated annually until 2020 using Dinamica Environment for Geoprocessing Objects (Dinamica EGO). This system is a state-of-the-art land use and cover change (LUCC) model which incorporates government policy, landscape maps, and other biophysical and anthropogenic datasets. Three studied scenarios: (i) business as usual, (ii) increased deforestation, and (iii) decreased deforestation showed more transition to agriculture from shrubland compared to forests, and consistent locations for most deforestation. The probability of conversion to agriculture is strongly tied to areas with the smallest patches of original biome remaining. Increases in agricultural revenue are projected to continue with a loss of 25% of the remaining Cerrado land in the next decade if profit is maximized. The addition of biodiversity value as a tax on land sale prices, estimated at over $750,000,000 USD using the cost of extracting and maintaining current species ex-situ, can save more than 1 million hectares of shrubland with minimal effects on the economy of the State of Minas Gerais. With environmental policy determining rates of deforestation and economics driving the location of land clearing, site-specific protection or market accounting of externalities is needed to balance economic development and conservation. PMID- 26371877 TI - Survivors in the Margins: The Invisibility of Violence Against Older Women. AB - Violence against older women exists in the margins between domestic violence and elder abuse, with neither field adequately capturing the experiences of older women survivors of intimate partner violence (IPV). This commentary explores this oversight, identifying how the lack of gender analysis in the elder abuse field exacerbates older survivors' invisibility when the wider violence against women (VAW) field lacks a lifespan approach to abuse. Examining the impact of generational and aging factors on how older women experience IPV, we assert that the VAW field may be overlooking a wider population of survivors than previously thought. PMID- 26371878 TI - Hepatitis B and C Co-Infections in Some HIV-Positive Populations in Cameroon, West Central Africa: Analysis of Samples Collected Over More Than a Decade. AB - As people infected with the human immunodeficiency virus (HIV) in Sub-Saharan Africa live longer due to availability of antiretroviral treatment (ART), so is the rise of associated infections with their burdens on patients. But reliable data on the prevalence of co-infection with hepatitis B (HBV) or C (HCV) still remains sparse and many individuals with HIV do not know their co-infection status. This study attempted to estimate the seroprevalence and identify risk factors associated with hepatitis B and/or C co-infections in HIV-infected individuals from five Regions of Cameroon by screening 531 HIV infected subjects for the presence of HBV surface antigen (HBsAg) and antibodies to HCV (HCV-Ab). A Screening and a confirmatory Enzyme linked immunosorbent assay were used to detect presence of markers of infection. CD4 count levels were also examined. The results indicate that of the 531 participants, 68% were females and 32% males. Mean CD4 count was ~400 cells/MUl. Seroprevalence rates for HBsAg and HCV-Ab were 23.7%, and 7.2%, respectively. Associations assessed using logistic regression revealed that HBsAg but not HCV-Ab positivity was linked to age, lower CD4 count and residing in an urban rather than in a rural setting. This high prevalence of co-infection with HBV raises the urgent need to systematically screen all newly diagnosed HIV cases for co-infection in Cameroon and other regions of sub-Saharan Africa where HIV accounts for the majority of the global infection, so as to improve management strategies for HBV infection and ART implementation. PMID- 26371879 TI - Increased pulsatility in the fetal ductus venosus is not related to altered cardiac strain in high-risk pregnancies. AB - OBJECTIVE: Blood flow velocity patterns in fetal veins are considered to reflect cardiac function, but have not been convincingly documented. The aim of this study was to generate reference values for fetal cardiac strain and compare it with results in fetuses with signs of increased venous pulsatility. METHODS: Cardiac four-chamber loops were prospectively stored and analyzed for strain and strain rate in a cohort of 250 healthy fetuses. The results were compared with recordings in 38 fetuses with increased vascular impedance in the umbilical artery, including several with abnormal blood flow velocities in the ductus venosus (DVs) and umbilical vein. RESULTS: In the control group, strain rate was slightly higher in the right ventricle, but strain and velocities were similar. There was a significant effect of frame rate on the values of strain and strain rate, but not on velocity. No differences in cardiac strain or strain rate were observed between the control group and the compromised fetuses. There was no correlation between changes in venous blood flow and cardiac strain. CONCLUSIONS: Increased venous pulsatility was not related to fetal cardiac strain. This might indicate that the DVs does not primarily open due to increased central venous pressure and that cardiac strain is affected late in the process of moderate fetal hypoxia. PMID- 26371880 TI - Determinants of the Final Size and Case Rate of Nosocomial Outbreaks. AB - Different nosocomial pathogen species have varying infectivity and durations of infectiousness, while the transmission route determines the contact rate between pathogens and susceptible patients. To determine if the pathogen species and transmission route affects the size and spread of outbreaks, we perform a meta analysis that examines data from 933 outbreaks of hospital-acquired infection representing 14 pathogen species and 8 transmission routes. We find that the mean number of cases in an outbreak is best predicted by the pathogen species and the mean number of cases per day is best predicted by the species-transmission route combination. Our fitted model predicts the largest mean number of cases for Salmonella outbreaks (22.3) and the smallest mean number of cases for Streptococci outbreaks (8.5). The largest mean number of cases per day occurs during Salmonella outbreaks spread via the environment (0.33) and the smallest occurs for Legionella outbreaks spread by multiple transmission routes (0.005). When combined with information on the frequency of outbreaks these findings could inform the design of infection control policies in hospitals. PMID- 26371881 TI - Differential impact of emotional task relevance on three indices of prioritised processing for fearful and angry facial expressions. AB - It is commonly assumed that threatening expressions are perceptually prioritised, possessing the ability to automatically capture and hold attention. Recent evidence suggests that this prioritisation depends on the task relevance of emotion in the case of attention holding and for fearful expressions. Using a hybrid attentional blink (AB) and repetition blindness (RB) paradigm we investigated whether task relevance also impacts on prioritisation through attention capture and perceptual salience, and if these effects generalise to angry expressions. Participants judged either the emotion (relevant condition) or gender (irrelevant condition) of two target facial stimuli (fearful, angry or neutral) imbedded in a stream of distractors. Attention holding and capturing was operationalised as modulation of AB deficits by first target (T1) and second target (T2) expression. Perceptual salience was operationalised as RB modulation. When emotion was task-relevant (Experiment 1; N = 29) fearful expressions captured and held attention, and were more perceptually salient than neutral expressions. Angry expressions captured attention, but were less perceptually salient and capable of holding attention than fearful and neutral expressions. When emotion was task-irrelevant (Experiment 2; N = 30), only fearful attention capture and perceptual salience effects remained significant. Our findings highlight the importance for threat-prioritisation research to heed both the type of threat and prioritisation investigated. PMID- 26371882 TI - Extensive Analysis of GmFTL and GmCOL Expression in Northern Soybean Cultivars in Field Conditions. AB - The FLOWERING LOCUS T (FT) gene is a highly conserved florigen gene among flowering plants. Soybean genome encodes six homologs of FT, which display flowering activity in Arabidopsis thaliana. However, their contributions to flowering time in different soybean cultivars, especially in field conditions, are unclear. We employed six soybean cultivars with different maturities to extensively investigate expression patterns of GmFTLs (Glycine max FT-like) and GmCOLs (Glycine max CO-like) in the field conditions. The results show that GmFTL3 is an FT homolog with the highest transcript abundance in soybean, but other GmFTLs may also contribute to flower induction with different extents, because they have more or less similar expression patterns in developmental-, leaf-, and circadian-specific modes. And four GmCOL genes (GmCOL1/2/5/13) may confer to the expression of GmFTL genes. Artificial manipulation of GmFTL expression by transgenic strategy (overexpression and RNAi) results in a distinct change in soybean flowering time, indicating that GmFTLs not only impact on the control of flowering time, but have potential applications in the manipulation of photoperiodic adaptation in soybean. Additionally, transgenic plants show that GmFTLs play a role in formation of the first flowers and in vegetative growth. PMID- 26371883 TI - Time-Course Analysis of Protein and Lipid Oxidation in the Brains of Yac128 Huntington's Disease Transgenic Mice. AB - Huntington's disease (HD) is caused by an expansion of cytosine-adenine-guanine (CAG) repeats within the coding region of the HD gene, which expresses the protein huntingtin and is characterized by selective degeneration of specific neuronal populations, mainly in the striatum and the cortex. The mechanisms that account for this selective neuronal death are multifaceted, but oxidative stress might play an important role in this process. To determine whether changes in the intracellular redox state will result in oxidative damage to cellular macromolecules with disease progression, we analyzed levels of lipid peroxidation (with the thiobarbituric acid reactive substances [TBARS] assay) and protein carbonyl formation (using the 2,4-dinitrophenylhydrazine reaction) in the cerebellum, cerebral cortex, prefrontal cortex, striatum, and hippocampus of the YAC128 HD mouse model at 3, 6, and 12 months of age. With the exception of a transient increase in protein carbonyl levels in the YAC128 prefrontal cortex at 6 months of age, levels of lipid peroxidation and protein oxidation were not significantly different between YAC128 mice and their age-matched wild-type counterparts in any of the brain regions analyzed up to 12 months of age. However, age-related increases in oxidative stress were observed in various brain regions. These results suggest that lipid and protein oxidative damage is not a major contributor to neurodegeneration in the YAC128 brain up to 12 months of age. PMID- 26371884 TI - Getting a Good Night's Sleep in Adolescence: Do Strategies for Coping With Stress Matter? AB - Getting a good night's sleep is challenging for adolescents because of early school start times and adolescents' substantial social and physical changes. We tested whether key indices of sleep health are associated with usual styles of coping with stress and interpersonal conflict in healthy black and white adolescents. Two hundred forty-two (57% female, 56% black) high school students completed daily sleep diaries, questionnaires, and actigraphy across a school week. Linear regression models tested associations, independent of race, gender, and other covariates. Students who reported using disengagement coping exhibited poor sleep health. They had shorter sleep duration, more fragmented sleep, delayed sleep, and increased daytime sleepiness. Unexpectedly, positive engagement coping was related to daytime sleepiness and delayed sleep, although not in models that included disengagement coping. Coping strategies may be an important influence on adolescent sleep. Future research should evaluate the antecedent-consequent relationships among coping, sleep, and stress. PMID- 26371885 TI - Determinants of Primary School Non-Enrollment and Absenteeism: Results from a Retrospective, Convergent Mixed Methods, Cohort Study in Rural Western Kenya. AB - BACKGROUND: Education is a key element in the socioeconomic development required to improve quality of life in Kenya. Despite the introduction of free primary education, primary school enrollment and attendance levels remain low. Drawing on qualitative and quantitative data, this study explores the determinants of non enrollment and absenteeism in rural western Kenya and potential mitigation strategies to address these issues. METHODS: The study was conducted in Bwaliro village in rural western Kenya. A random sample of 64 students was obtained by blocking the village primary school's student population according to grade level, gender, and orphan status. Qualitative and quantitative data were collected through interviews with parents, guardians, and key informants, and focus group discussions with students. Quantitative data were compared using chi square tests, Student's T-test, and Poisson regressions. Qualitative data were analyzed using thematic content analysis. RESULTS: Malaria, menstruation, and lack of money were among the most notable determinants of primary school dropout and absenteeism, and these factors disproportionately impacted orphans and female students. Potential mitigation strategies suggested by the community included provision of malaria treatment or prevention, reduction in education costs, expansion of the established school-feeding program, and provision of sanitary pads. CONCLUSION: Despite free primary education, numerous factors continue to prevent children in rural western Kenya from attending primary school. The findings suggest that interventions should primarily target orphaned and female students. Prior to implementation, suggested mitigation strategies should be assessed for cost-effectiveness. PMID- 26371886 TI - Molecular Profiling of a Rare Rosette-Forming Glioneuronal Tumor Arising in the Spinal Cord. AB - Rosette-forming glioneuronal tumor (RGNT) of the IV ventricle is a rare and recently recognized brain tumor entity. It is histologically composed by two distinct features: a glial component, resembling pilocytic astrocytoma, and a component forming neurocytic rosettes and/or perivascular rosettes. Herein, we describe a 33-year-old man with RGNT arising in the spinal cord. Following an immunohistochemistry validation, we further performed an extensive genomic analysis, using array-CGH (aCGH), whole exome and cancer-related hotspot sequencing, in order to better understand its underlying biology. We observed the loss of 1p and gain of 1q, as well as gain of the whole chromosomes 7, 9 and 16. Local amplifications in 9q34.2 and 19p13.3 (encompassing the gene SBNO2) were identified. Moreover, we observed focal gains/losses in several chromosomes. Additionally, on chromosome 7, we identified the presence of the KIAA1549:BRAF gene fusion, which was further validated by RT-PCR and FISH. Across all mutational analyses, we detected and validated the somatic mutations of the genes MLL2, CNNM3, PCDHGC4 and SCN1A. Our comprehensive molecular profiling of this RGNT suggests that MAPK pathway and methylome changes, driven by KIAA1549:BRAF fusion and MLL2 mutation, respectively, could be associated with the development of this rare tumor entity. PMID- 26371888 TI - Publications and the foundation programme application. PMID- 26371887 TI - Derivation and characterization of porcine vocal fold extracellular matrix scaffold. AB - OBJECTIVES/HYPOTHESIS: To optimize decellularization of porcine vocal folds (VF) and quantify human bone marrow-derived mesenchymal stem cell (BM-MSC) interactions with this matrix to provide a foundation for regenerative approaches to VF repair. STUDY DESIGN AND METHODS: Vocal folds were dissected from porcine larynges and three decellularization protocols were compared, each consisting of washes and mechanical agitations with different combinations of reagents. DNA content was analyzed via Quant-iT Picogreen assay and hematoxylin and eosin staining. Bone marrow-derived MSCs were then seeded onto the decellularized VF matrices. Morphology, metabolic activity, DNA content, and gene expression were assessed using LIVE/DEAD Cell Viability, alamarBlue Cell Viability Assay, Quant iT Picogreen assay, and quantitative polymerase chain reaction, respectively. RESULTS: The most successful decellularization protocol removed 95% DNA content within 1 day, compared to several days required for previously described protocols. Histology confirmed the retention of extracellular matrix (ECM) and its components, including glycosaminoglycans, collagen, and fibrin, while void of nuclear/cellular content. Decellularized scaffolds were then seeded with BM-MSCs. Similar DNA quantities were observed after 24 hours of seeding within the VF-ECM scaffold when compared to cells on tissue culture plastic (TCP). LIVE/DEAD staining of the seeded VF-ECM confirmed excellent cell viability, and the metabolic activity of BM-MSCs increased significantly on VF-ECM compared to TCP. Endoglin gene expression decreased, suggestive of differentiation. CONCLUSION: Porcine VFs can be efficiently decellularized within 5 hours using a combination of sodium deoxycholate and peracetic acid. Decellularized VF-ECM supported attachment and growth of human BM-MSCs, with evidence of differentiation. LEVEL OF EVIDENCE: N/A. PMID- 26371889 TI - The effect of maternal anemia on maternal and neonatal outcomes in twin pregnancies. AB - OBJECTIVE: The objective of this study is to investigate the effect of second trimester anemia on maternal and perinatal outcomes in twin pregnancies. METHODS: A retrospective population-based study was conducted, comparing maternal and neonatal outcomes in women carrying twins, with second trimester anemia (defined as hemoglobin < 10 g/dl) to those without anemia (defined as hemoglobin > or equal to 10 g/dl). Deliveries occurred in a tertiary medical center in 2013. RESULTS: During the study period, there were 307 twin deliveries. Hemoglobin levels were available for 247 (80.4%) twins; 66 (26.7%) of these had anemia (<10 g/dl) during the second trimester. Women with second trimester anemia had a higher parity (p=0.03), and needed more blood transfusions than those with hemoglobin level > or equal to 10 g/dl (OR = 1.6; 95% CI 1.11-2.43, p < 0.001). No significant differences were noted between the groups regarding other obstetrical outcomes or regarding perinatal outcomes. CONCLUSION: Second trimester anemia in women carrying twins is associated with a high parity and increases the risk for blood transfusions. However, in our population, maternal anemia in twin gestations does not increase the risk for adverse perinatal outcome. PMID- 26371890 TI - Daily Physical Activity and Cognitive Function Variability in Older Adults. AB - Physical activity (PA) is believed to preserve cognitive function in older adulthood, though little is known about these relationships within the context of daily life. The present microlongitudinal pilot study explored within- and between-person relationships between daily PA and cognitive function and also examined within-person effect sizes in a sample of community-dwelling older adults. Fifty-one healthy participants (mean age = 70.1 years) wore an accelerometer and completed a cognitive assessment battery for five days. There were no significant associations between cognitive task performance and participants' daily or average PA over the study period. Effect size estimates indicated that PA explained 0-24% of within-person variability in cognitive function, depending on cognitive task and PA dose. Results indicate that PA may have near-term cognitive effects and should be explored as a possible strategy to enhance older adults' ability to perform cognitively complex activities within the context of daily living. PMID- 26371893 TI - High-directionality fiber-chip grating coupler with interleaved trenches and subwavelength index-matching structure. AB - We present the first experimental demonstration of a new fiber-chip grating coupler concept that exploits the blazing effect by interleaving the standard full (220 nm) and shallow etch (70 nm) trenches in a 220 nm thick silicon layer. The high directionality is obtained by controlling the separation between the deep and shallow trenches to achieve constructive interference in the upward direction and destructive interference toward the silicon substrate. Utilizing this concept, the grating directionality can be maximized independent of the bottom oxide thickness. The coupler also includes a subwavelength-engineered index-matching region, designed to reduce the reflectivity at the interface between the injection waveguide and the grating. We report a measured fiber-chip coupling efficiency of -1.3 dB, the highest coupling efficiency achieved to date for a surface grating coupler in a 220 nm silicon-on-insulator platform fabricated in a conventional dual-etch process without high-index overlays or bottom mirrors. PMID- 26371892 TI - The prolongation of pulse transit time after a stellate ganglion block: An objective indicator of successful block. AB - BACKGROUND: An objective marker of successful stellate ganglion block (SGB) does not exist. Horner syndrome, which is currently used to determine the effect of SGB, is sometimes ambiguous. OBJECTIVE: To investigate the change in pulse transit time (PTT) after SGB, and to evaluate the utility of PTT as an objective measure of successful SGB. METHODS: Eight patients (34 to 62 years of age) underwent SGB for diagnosis or treatment of sympathetically mediated pain of the upper extremities. The success of the SGB was determined according to the presence of Horner syndrome. Electrocardiography, noninvasive blood pressure measurements and pulse oximetry were used to monitor all patients. PTT was measured using data saved on the WinDaq waveform browser. RESULTS: PTT was measured at baseline and 3 min, 5 min and 10 min after the injection of a local anesthetic. At 3 min after SGB, the mean (+/- SD) PTT was 624.6+/-20.5 ms. At 5 min after injection, the mean PTT was 630.8+/-17.5 ms. Prolonged PTT at 5 min was found to return to the baseline value at 10 min (613.6+/-14.7 ms). According to the Friedman test, the differences from baseline values were significant (P=0.008). CONCLUSION: Measurement of PTT at 5 min after local anesthetic injection can help to objectively determine the success of SGB. PMID- 26371891 TI - Nitrous oxide persistently alleviates pain hypersensitivity in neuropathic rats: A dose-dependent effect. AB - BACKGROUND: Despite numerous pharmacological approaches, there are no common analgesic drugs that produce meaningful relief for the majority of patients with neuropathic pain. Although nitrous oxide (N2O) is a weak analgesic that acts via opioid-dependent mechanisms, it is also an antagonist of the N-methyl-D-aspartate receptor (NMDAR). The NMDAR plays a critical role in the development of pain sensitization induced by nerve injury. OBJECTIVE: Using the chronic constriction injury of the sciatic nerve in male rats as a preclinical model of neuropathic pain, the first aim of the present study was to evaluate the lowest N2O concentration and the shortest time of N2O postinjury exposure that would produce persistent relief of neuropathic pain. The second aim was to compare the effects of N2O with gabapentin, a reference drug used in human neuropathic pain relief. METHODS: Changes in the nociceptive threshold were evaluated using the paw pressure vocalization test in rats. RESULTS: Among the various N2O concentrations tested, which ranged from 25% to 50%, only 50% N2O single exposure for 1 h 15 min induced a persistent (minimum of three weeks) and significant (60%) reduction in pain hypersensitivity. A single gabapentin dose (75 mg/kg to 300 mg/kg, intraperitoneally) induced an acute (1 h to 1 h 30 min) dose-dependent effect, but not a persistent effect such as that observed with N2O. CONCLUSIONS: These preclinical results suggest that N2O is advantageous for long-lasting neuropathic pain relief after sciatic nerve injury compared with other drugs used in humans such as gabapentinoids or NMDAR antagonists. The present preclinical study provides a rationale for developing comparative clinical studies. PMID- 26371894 TI - Growth, spectroscopy, and laser performance of a 2.79 MUm Cr,Er,Pr:GYSGG radiation-resistant crystal. AB - We demonstrate the growth, spectroscopy, and laser performance of a 2.79 MUm Cr,Er,Pr:GYSGG radiation-resistant crystal. The lifetimes for the upper laser level (4)I(11/2) and lower laser level (4)I(13/2) are 0.59 and 0.84 ms, respectively, which are due to the doping of the Pr(3+) ions. A maximum pulse energy of 278 mJ operated at 10 Hz and 2.79 MUm is obtained when pumped with a flash lamp, which corresponds to the electrical-to-optical efficiency of 0.6% and a slope efficiency of 0.7%. A maximum average power of 2.9 W at 60 Hz is achieved, which corresponds to the electrical-to-optical efficiency of 0.4% and slope efficiency of 0.8%. Compared with a Cr,Er:YSGG crystal, the Cr,Er,Pr:GYSGG crystal can be operated at a higher pulse repetition rate. These results suggest that doping deactivator Pr(3+) ions can effectively decrease the lower laser level lifetime and improve the laser repetition rate. Therefore, the application fields and range of the Cr,Er,Pr:GYSGG laser can be extended greatly due to its properties of radiation resistance and high repetition frequency. PMID- 26371895 TI - Optical injection locking-based amplification in phase-coherent transfer of optical frequencies. AB - We demonstrate the use of an optical injection phase locked loop (OIPLL) as a regenerative amplifier for optical frequency transfer applications. The optical injection locking provides high gain within a narrow bandwidth (<100 MHz) and is capable of preserving the fractional frequency stability of the incoming carrier to better than 10(-18) at 1000 s. The OIPLL was tested in the field as a mid-span amplifier for the transfer of an ultrastable optical carrier, stabilized to an optical frequency standard, over a 292 km long installed dark fiber link. The transferred frequency at the remote end reached a fractional frequency instability of less than 1*10(-19) at averaging time of 3200 s. PMID- 26371896 TI - Diffuse-light all-solid-state invisibility cloak. AB - An ideal invisibility cloak makes arbitrary macroscopic objects within the cloak indistinguishable from its surrounding-for all directions, illumination patterns, polarizations, and colors of visible light. Recently, we have approached such an ideal cloak for the diffusive regime of light propagation using a core-shell geometry and a mixture of water and white wall paint as the surrounding. Here, we present an all-solid-state version based on polydimethylsiloxane doped with titania nanoparticles for the surrounding/shell and on a high-reflectivity microporous ceramic for the core. By virtue of reduced effects of absorption, especially from the core, the cloaking performance and the overall light throughput are improved significantly. PMID- 26371897 TI - Channel add-drop filter based on dual photonic crystal cavities in push-pull mode. AB - We demonstrate an add-drop filter based on a dual photonic crystal nanobeam cavity system that emulates the operation of a traveling wave resonator, and, thus, provides separation of the through and drop port transmission from the input port. The device is on a 3*3 mm chip fabricated in an advanced microelectronics silicon-on-insulator complementary metal-oxide semiconductor (SOI CMOS) process (IBM 45 nm SOI) without any foundry process modifications. The filter shows 1 dB of insertion loss in the drop port with a 3 dB bandwidth of 64 GHz, and 16 dB extinction in the through port. To the best of our knowledge, this is the first implementation of a port-separating, add-drop filter based on standing wave cavities coupled to conventional waveguides, and demonstrates a performance that suggests potential for photonic crystal devices within optical immersion lithography-based advanced CMOS electronics-photonics integration. PMID- 26371899 TI - Demonstration of a high-energy, narrow-bandwidth, and temporally shaped fiber regenerative amplifier. AB - We report a high-energy and high-gain fiber regenerative amplifier for narrow bandwidth nanosecond laser pulses that uses a Yb-doped photonic crystal fiber. The input pulse energy is 270 pJ for a 3.5 ns laser pulse with 0.3 nm (FWHM) bandwidth. At a pump laser power of 8.6 W at 974 nm, pulse energies up to 746 MUJ with 1.2% (rms) energy stability are generated. To the best of our knowledge, this is the highest energy obtained in a fiber-based regenerative amplifier. A high-energy, nearly diffraction-limited, single-mode beam with a high gain of 64 dB shows promise for future application in the front ends of high-power laser facilities. PMID- 26371898 TI - Free-space optical communications using orbital-angular-momentum multiplexing combined with MIMO-based spatial multiplexing. AB - We explore the potential of combining the advantages of multiple-input multiple output (MIMO)-based spatial multiplexing with those of orbital angular momentum (OAM) multiplexing to increase the capacity of free-space optical (FSO) communications. We experimentally demonstrate an 80 Gbit/s FSO system with a 2*2 aperture architecture, in which each transmitter aperture contains two multiplexed data-carrying OAM modes. Inter-channel crosstalk effects are minimized by the OAM beams' inherent orthogonality and by the use of 4*4 MIMO signal processing. Our experimental results show that the bit-error rates can reach below the forward error correction limit of 3.8*10(-3) and the power penalties are less than 3.6 dB for all channels after MIMO processing. This indicates that OAM and MIMO-based spatial multiplexing could be simultaneously utilized, thereby providing the potential to enhance system performance. PMID- 26371900 TI - Tunable frequency-up/down conversion in gas-filled hollow-core photonic crystal fibers. AB - Based on the interplay between photoionization and Raman effects in gas-filled photonic crystal fibers, we propose a new optical device to control frequency conversion of ultrashort pulses. By tuning the input-pulse energy, the output spectrum can be either down-converted, up-converted, or even frequency-shift compensated. For low input energies, the Raman effect is dominant and leads to a redshift that increases linearly during propagation. For larger pulse energies, photoionization starts to take over the frequency-conversion process and induces a strong blueshift. The fiber-output pressure can be used as an additional degree of freedom to control the spectrum shift. PMID- 26371901 TI - Focal varying microlens array. AB - We report a novel microlens array with different curvature unit lenses (MLADC) fabricated with femtosecond laser direct writing technology. The MLADC consisted of hexagonal hyperboloid unit microlenses, which have different heights and curvatures from others. The unique optical performance of imaging and focusing capability were demonstrated. An object was imaged at different positions from the MLADC by unit lenses, as the ability of adjusting the curvature of the image plane for overall MLADC. In addition, the experiment had a good agreement with simulation results, which was based on the analysis of the finite element method. The novel MLADC will have important applications in improving the performance of optical systems, especially in field curvature correction and real-time three dimensional imaging. PMID- 26371902 TI - Ultrafast pulses from a mid-infrared fiber laser. AB - Ultrafast laser pulses at mid-infrared wavelengths (2-20 MUm) interact strongly with molecules due to the resonance with their vibration modes. This enables their application in frequency comb-based sensing and laser tissue surgery. Fiber lasers are ideal to achieve these pulses, as they are compact, stable, and efficient. We extend the performance of these lasers with the production of 6.4 kW at a wavelength of 2.8 MUm with complete electric field retrieval using frequency-resolved optical gating techniques. Contrary to the problems associated with achieving a high average power, fluoride fibers have now shown the capability of operating in the ultrafast, high-peak-power regime. PMID- 26371903 TI - Surface plasmon coupling for suppressing p-GaN absorption and TM-polarized emission in a deep-UV light-emitting diode. AB - The radiated power enhancement (suppression) of an in- (out-of-) plane-oriented radiating dipole at a desired emission wavelength in the deep-ultraviolet (UV) range when it is coupled with a surface plasmon (SP) resonance mode induced on a nearby Al nanoparticle (NP) is demonstrated. Also, it is found that the enhanced radiated power propagates mainly in the direction from the Al NP toward the dipole. Such SP coupling behaviors can be used for suppressing the transverse magnetic (TM)-polarized emission, enhancing the transverse-electric-polarized emission, and reducing the UV absorption of the p-GaN layer in an AlGaN-based deep-UV light-emitting diode by embedding a sphere-like Al NP in its p-AlGaN layer. PMID- 26371904 TI - Comparative analysis of four-wave mixing of optical pulses in slow- and fast light regimes of a silicon photonic crystal waveguide. AB - We present an in-depth study of four-wave mixing (FWM) of optical pulses in silicon photonic crystal waveguides. Our analysis is based on a rigorous model that includes all relevant linear and nonlinear optical effects and their dependence on the group velocity, as well as the influence of free carriers on pulse dynamics. In particular, we reveal key differences between FWM in the slow- and fast-light regimes and how they are related to the physical parameters of the pulses and waveguide. Finally, we illustrate how these results can be used to design waveguides with optimized FWM conversion efficiency. PMID- 26371905 TI - High-order micro-ring resonator with perfect transmission using symmetrical Fibonacci structures. AB - A symmetrical Fibonacci micro-ring resonator (SFMR) has been presented to avoid the coupled resonator optical waveguide (CROW) bottle, which is a bottle-shaped distribution for high orders in transmission spectra. The SFMR features three advantages that improve filtering quality compared to that provided by traditional periodic micro-ring resonators. First, sharper resonances are obtained by eliminating the CROW bottle from the mini gaps that appear in the major-band region. Second, peaks with perfect transmission are always obtained without a radius and coupling modulation in the mini-band regions and major-band regions. Third, the full width at half-maximum of the band-edge peak decreases with the increasing generation order. PMID- 26371906 TI - Electromagnetically induced transparency based on guided-mode resonances. AB - We present a novel, electromagnetically induced transparency system based on guided-mode resonances and numerically demonstrate its transmission characteristics through finite-difference time-domain simulations. The system is composed of two planar dielectric waveguides and a subwavelength grating. It is shown that by coupling the two resonant guide modes with a low- and high-quality factor, a narrow transparency window is generated inside a broad background transmission dip produced by the guided-mode resonance. Our work could provide another efficient way toward the realization of electromagnetically induced transparency. PMID- 26371907 TI - Time-averaged photon-counting digital holography. AB - Time-averaged holography has been using photo-emulsions (early stage) and digital photo-sensitive arrays (later) to record holograms. We extend the recording possibilities by utilizing a photon-counting camera, and we further investigate the possibility of obtaining accurate hologram reconstructions in rather severe experimental conditions. To achieve this, we derived an expression for fringe function comprising the main parameters affecting the hologram recording. Influence of the main parameters, namely the exposure time and the number of averaged holograms, is analyzed by simulations and experiments. It is demonstrated that taking long exposure times can be avoided by averaging over many holograms with the exposure times much shorter than the vibration cycle. Conditions in which signal-to-noise ratio in reconstructed holograms can be substantially increased are provided. PMID- 26371908 TI - High accuracy measurement of the ground-state hyperfine splitting in a 113Cd+ microwave clock. AB - A microwave frequency standard based on laser-cooled (113)Cd(+) ions has been developed in recent years, and the short-term frequency instability is measured to be 6.1*10(-13)/?tau. By comparing the Cd(+) clock to a superior frequency reference, the ground-state hyperfine splitting of (113)Cd(+) is measured precisely to be 15199862855.0192(10) Hz with a fractional precision of 6.6*10( 14). This result is consistent with previous results, and the measurement precision is improved by nearly one order more than the best result reported before. PMID- 26371909 TI - Slow-light plasmonic metamaterial based on dressed-state analog of electromagnetically induced transparency. AB - We consider a simple configuration for realizing one-dimensional slow-light metamaterials with large bandwidth-delay products using stub-shaped Fabry-Perot resonators as building blocks. Each meta-atom gives rise to large group indices because of a classical analog of the dressed-state picture of electromagnetically induced transparency. By connecting up to eight meta-atoms, we find bandwidth delay products over unity and group indices approaching 100. Our approach is quite general and can be applied to any type of Fabry-Perot resonators and tuned to different operating wavelengths. PMID- 26371910 TI - Dispersive waves induced by self-defocusing temporal solitons in a beta-barium borate crystal. AB - We experimentally observe dispersive waves in the anomalous dispersion regime of a beta-barium-borate (BBO) crystal, induced by a self-defocusing few-cycle temporal soliton. Together the soliton and dispersive waves form an energetic octave-spanning supercontinuum. The soliton was excited in the normal dispersion regime of BBO through a negative cascaded quadratic nonlinearity. Using pump wavelengths from 1.24 to 1.4 MUm, dispersive waves are found from 1.9 to 2.2 MUm, agreeing well with calculated resonant phase-matching wavelengths due to degenerate four-wave mixing to the soliton. We also observe resonant radiation from nondegenerate four-wave mixing between the soliton and a probe wave, which was formed by leaking part of the pump spectrum into the anomalous dispersion regime. We confirm the experimental results through simulations. PMID- 26371911 TI - Infrared hot-carrier photodetection based on planar perfect absorber. AB - Hot-carrier based photodetectors are independent on the semiconductor bandgap, thus paving a new paradigm of photovoltaic conversion. Herein, we propose a non nanostructured and multilayered metal/insulator/transparent conductive oxide/silica/reflector system, and explore in detail the optical response and the electrical transport in the device via the finite-element electromagnetic simulation and the probability-based analytical carrier-transport calculation. Results show that the planar system can function as a planar perfect absorber at the targeted wavelength under the inbuilt cavity resonance with a very high tunability by tailoring the cavity length and the metal thickness. Moreover, a strong asymmetrical absorption is formed in the two electrode layers, yielding strong unidirectional photocurrents and output power densities. This Letter suggests a more simple and feasible way to realize hot-carrier infrared photodetectors. PMID- 26371912 TI - Optical injection and spectral filtering of high-power ultraviolet laser diodes. AB - We demonstrate injection locking of high-power laser diodes operating at 397 nm. We achieve stable operation with an injection power of ~100 MUW and a slave laser output power of up to 110 mW. We investigate the spectral purity of the slave laser light via photon scattering experiments on a single trapped (40)Ca(+) ion. We show that it is possible to achieve a scattering rate indistinguishable from that of monochromatic light by filtering the laser light with a diffraction grating to remove amplified spontaneous emission. PMID- 26371913 TI - High-power, high-repetition-rate, Yb-fiber laser based femtosecond source at 355 nm. AB - We report on the development of a high-power, high-repetition-rate, fiber laser based source of ultrafast ultraviolet (UV) radiation. Using single-pass second harmonic generation and subsequent sum-frequency generation (SFG) of an ultrafast ytterbium fiber at 1064 nm in 1.2 and 5 mm long bismuth triborate (BIBO) crystals, respectively, we have generated UV output power as high as 1.06 W at 355 nm with single-pass near-infrared-to-UV conversion efficiency of ~22%. The source has output pulses of temporal and spectral widths of ~576 fs and 1.6 nm, respectively, at 78 MHz repetition rate. For given crystals and laser parameters, we have experimentally verified that the optimum conversion efficiency of the SFG process requires interacting pump beams to have the same confocal parameters. We also present a systematic study on the power ratio of pump beams influencing the overall conversion of the UV radiation. The UV source has a peak-to-peak short term power fluctuation of <2.2%, with a power drift of 0.76%/h associated to different loss mechanisms of the BIBO crystal at UV wavelengths. At tight focusing, the BIBO crystal has a broad angular acceptance bandwidth of (~2 mrad.cm) for SFG of the femtosecond laser. PMID- 26371914 TI - Electromagnetic diffraction properties of randomly aligned one-dimensional cylinders. AB - A new approach to electromagnetically analyzing random structures is proposed. By increasing a grating period consisting of a deterministic random structure, optical performance of the element approaches a certain converged value. Thus, characterizing random structures becomes possible in a single-run computation without a statistical procedure. We demonstrate the performance of this method using one-dimensional cylinder arrays. PMID- 26371915 TI - Spectroscopic sensing of reflection optical activity in achiral AgGaS2. AB - Optical activity is a fundamental effect of electrodynamics that was discovered more than 200 years ago. While optical activity is typically recognized by the rotation of the polarization of light as it propagates through a bulk medium, in certain configurations, the specular reflection of light on the surface of a material is also sensitive to its optical activity. Here, we show that the ellipsometric analysis of the light reflected at the surface of a gyrotropic but achiral crystal of AgGaS(2) allows the spectroscopic determination of its optical activity above the bandgap, where transmission methods are not applicable. This is the first clear spectroscopic determination of reflection optical activity in a crystal, and the values obtained are, to the best of our knowledge, the largest ever reported for a natural material. We also demonstrate that normal incidence transmission and reflection measurements probe different aspects of optical activity. PMID- 26371916 TI - Multimode Brillouin spectrum in a long tapered birefringent photonic crystal fiber. AB - We investigate the stimulated Brillouin scattering (SBS) in a long tapered birefringent solid-core photonic crystal fiber (PCF) and compare our results with a similar but untapered PCF. It is shown that the taper generates a broadband and multipeaked Brillouin spectrum, while significantly increasing the threshold power. Furthermore, we observe that the strong fiber birefringence gives rise to a frequency shift of the Brillouin spectrum which increases along the fiber. Numerical simulations are also presented to account for the taper effect and the birefringence. Our findings open a new means to control or inhibit the SBS by tapering photonic crystal fibers. PMID- 26371917 TI - All-silicon nanorod-based Dammann gratings. AB - Established diffractive optical elements (DOEs), such as Dammann gratings, whose phase profile is controlled by etching different depths into a transparent dielectric substrate, suffer from a contradiction between the complexity of fabrication procedures and the performance of such gratings. In this Letter, we combine the concept of geometric phase and phase modulation in depth, and prove by theoretical analysis and numerical simulation that nanorod arrays etched on a silicon substrate have a characteristic of strong polarization conversion between two circularly polarized states and can act as a highly efficient half-wave plate. More importantly, only by changing the orientation angles of each nanorod can the arrays control the phase of a circularly polarized light, cell by cell. With the above principle, we report the realization of nanorod-based Dammann gratings reaching diffraction efficiencies of 50%-52% in the C-band fiber telecommunications window (1530-1565 nm). In this design, uniform 4*4 spot arrays with an extending angle of 59 degrees *59 degrees can be obtained in the far field. Because of these advantages of the single-step fabrication procedure, accurate phase controlling, and strong polarization conversion, nanorod-based Dammann gratings could be utilized for various practical applications in a range of fields. PMID- 26371918 TI - Electromagnetically induced absorption in a nondegenerate three-level ladder system. AB - We investigate, theoretically and experimentally, the transmission of light through a thermal vapor of three-level ladder-type atoms, in the presence of two counterpropagating control fields. A simple theoretical model predicts the presence of electromagnetically induced absorption in this pure three-level system when the control field is resonant. Experimentally, we use (87)Rb in a large magnetic field of 0.62 T to reach the hyperfine Paschen-Back regime and realize a nondegenerate three-level system. Experimental observations verify the predictions over a wide range of detunings. PMID- 26371919 TI - Quantitative imaging of microvascular blood flow networks in deep cortical layers by 1310 nm MUODT. AB - There is growing interest in new neuroimage techniques that permit not only high resolution quantification of cerebral blood flow velocity (CBFv) in capillaries, but also a large field of view to map the CBFv network dynamics. Such image capabilities are of great importance for decoding the functional difference across multiple cortical layers under stimuli. To tackle the limitation of optical penetration depth, we present a new ultrahigh-resolution optical coherence Doppler tomography (MUODT) system at 1310 nm and compare it with a prior 800 nm MUODT system for mouse brain 3D CBFv imaging. We show that the new 1310 nm MUODT allows for dramatically increased depth (~4 times) of quantitative CBFv imaging to 1.4 mm, thus covering the full thickness of the mouse cortex (i.e., layers I-VI). Interestingly, we show that such a unique 3D CBFv imaging capability allows identification of microcirculatory redistribution across different cortical layers resulting from repeated cocaine exposures. PMID- 26371920 TI - Ho3+/Er3+ co-doped fluoride glass sensitized by Tm3+ pumped by a 1550 nm laser diode for efficient 2.0 MUm laser applications. AB - In the present Letter, a high-emission intensity of 2.0 MUm is reported for Ho(3+)/Er(3+) co-doped fluoride glass sensitized by Tm(3+) ions under 1550 nm excitation. The measured absorption spectra do not show clustering in the local ligand field, which also demonstrates that Er(3+) ions are efficiently excited by pumping and energy transfer (ET) to Ho(3+) and Tm(3+) ions. The enhanced Ho(3+):2.0 MUm emission has a maximum emission cross section (4.8*10(-21) cm(2)). An ET mechanism based on the enhanced 2.0 MUm emission and other reduced near-infrared emissions is discussed. Results show that the addition of Tm(3+) ions populates the Ho(3+):(5)I(7) level through the channel at the Tm(3+):(3)F(4) level between Er(3+) and Ho(3+) ions. The spectroscopic characteristics and thermal property of Er(3+)/Ho(3+)/Tm(3+) tri-doped ZBYA glass reveal that the material is an attractive host for 2.0 MUm lasers. PMID- 26371921 TI - Highly coherent modeless broadband semiconductor laser. AB - We report on the highly coherent modeless broadband continuous wave operation of a semiconductor vertical-external-cavity-surface-emitting laser. The laser design is based on a frequency-shifted-feedback scheme provided by an acousto-optic frequency shifter inserted in a linear or a ring traveling wave cavity. The gain mirror is a GaAs-based multiple quantum well structure providing large gain at 1.07 MUm. This laser exhibits a coherent optical spectrum over 1.27 nm (330 GHz) bandwidth, with 70 mW output power and a high beam quality. The light polarization is linear (>30 dB extinction ratio). The laser dynamics exhibits a low intensity noise close to class A regime, with a ~1.5 MHz cutoff frequency. The frequency noise spectral density shows a first-order low-pass like shape (130 kHz cutoff) leading to a Gaussian shape for homodyne interferometric signals. The measured beat width is ?54 kHz and the coherence time of ~19 MUs. No nonlinear effects are observed, showing dynamics very close to theory. PMID- 26371922 TI - 0.5 billion events per second time correlated single photon counting using CMOS SPAD arrays. AB - We present a digital architecture for fast acquisition of time correlated single photon counting (TCSPC) events from a 32*32 complementary metal oxide semiconductor (CMOS) single photon avalanche detector (SPAD) array (Megaframe) to the computer memory. Custom firmware was written to transmit event codes from 1024-TCSPC-enabled pixels for fast transfer of TCSPC events. Our 1024-channel TCSPC system is capable of acquiring up to 0.5*10(9) TCSPC events per second with 16 histogram bins spanning a 14 ns width. Other options include 320*10(6) TCSPC events per second with 256 histogram bins spanning either a 14 or 56 ns time window. We present a wide-field fluorescence microscopy setup demonstrating fast fluorescence lifetime data acquisition. To the best of our knowledge, this is the fastest direct TCSPC transfer from a single photon counting device to the computer to date. PMID- 26371923 TI - Mode-locked fiber laser based on chalcogenide microwires. AB - We report the first mode-locked fiber laser using a chalcogenide microwire as the nonlinear medium. The laser is passively mode-locked with nonlinear polarization rotation and can be adjusted for the emission of solitons or noise-like pulses. The use of the microwire leads to a mode-locking threshold at the microwatt level and shortens the cavity length by 4 orders of magnitude with respect to other lasers of its kind. The controlled birefringence of the microwire, combined with a linear polarizer in the cavity, enables multiwavelength laser operation with tunable central wavelength, switchable wavelength separation, and a variable number of laser wavelengths. PMID- 26371924 TI - Monolithically integrated dual-channel coherent receiver with widely tunable local oscillator for 100 Gbps dual-polarization quadrature phase shift keying applications. AB - We report implementation of a monolithically integrated 100 Gbps dual polarization quadrature phase shift keying (DP-QPSK) wavelength tunable coherent receiver on a 1 mm*3 mm die that consists of a tunable C-Band local oscillator with a 40 nm range, eight 30 GHz photodetectors, and two parallel 90 degrees optical hybrids. A BER of 10(-3) with an OSNR of 7.5 dB operating at 50 Gbps NRZ QPSK data per channel is reported. PMID- 26371925 TI - Circularly polarized carrier-envelope-phase stable attosecond pulse generation based on coherent undulator radiation. AB - In this Letter, we present a new method for generation of circularly polarized attosecond pulses. According to our calculations, shape-controlled, carrier envelope-phase stable pulses of several hundred nanojoule energy could be produced by exploitation of the coherent undulator radiation of an electron bunch. Our calculations are based on an existing particle accelerator system (FLASH II in DESY, Germany). We investigated the energy dependence of the attosecond pulses on the energy of electrons and the parameters of the radiator undulator, which generate the electromagnetic radiation. PMID- 26371926 TI - Solid hemoglobin-polymer phantoms for evaluation of biophotonic systems. AB - Stable tissue phantoms that incorporate the spectral absorption properties of hemoglobin would benefit a wide range of biophotonic technologies. Toward this end, we have developed and validated a novel polymer material incorporating hemoglobin. Our solid hemoglobin-polymer (SHP) material is fabricated by mixing liquid silicone base with a hemoglobin solution, followed by sonication and low temperature curing. The optical properties of samples were determined over 450 1000 nm using the inverse adding-doubling method and the Beer-Lambert law. Measurements indicated SHP optical stability over four months. Near-infrared spectroscopy and hyperspectral imaging measurements of SHP samples were performed to demonstrate the utility of this approach. SHP materials have the potential to improve tissue-simulating phantoms used for development, evaluation, and standardization of optical devices for oximetry and other applications. PMID- 26371927 TI - Solving the radiative transfer equation with a mathematical particle method. AB - We solve the radiative transfer equation (RTE) using a recently proposed mathematical particle method, originally developed for solving general functional equations. We show that, in the case of the RTE, it gives several advantages, such as handling arbitrary boundary conditions and phase functions and avoiding numerical instability in strongly forward-scattering media. We also solve the RTE, including fluorescence, and an example is shown with a fluorescence cascade where light is absorbed and emitted in several steps. We show that the evaluated particle method is straightforward to implement, which is in contrast with many traditional RTE solvers, but a potential drawback is the tuning of the method parameters. PMID- 26371928 TI - Widely tunable mode-locked fiber laser using carbon nanotube and LPG W-shaped filter. AB - A widely tunable mode-locked fiber laser using a carbon nanotube absorber and a fiber-optic W-shaped spectral filter is presented. The W-shaped filter is constructed by sandwiching a phase-shifted long-period grating between two LPGs of different periods. By adjusting the temperature of the W-shaped filter from 23 degrees C to 100 degrees C, the central wavelength of the mode-locked fiber laser can be continuously tuned from 1597 to 1553 nm. The tuning range is further extended to 1531.6 nm when a shorter erbium-doped fiber is used in the fiber oscillator. The experimental results reveal that the large thermal tunability of the proposed LPG filter provides an effective approach to achieve compact widely tunable mode-locked fiber lasers covering both C and L bands. PMID- 26371929 TI - Multilayer bandpass filter with extended lower and upper stop bands. AB - We propose a novel design for a multilayer bandpass filter in which every resonant dielectric layer is separated from adjacent dielectric layers or from the ambient by a nonresonant grating of strip conductors on the layer interface. Here, every grating acts as a mirror with specified transparency. Relative to the conventional multilayer bandpass filter with multilayer dielectric mirrors, the proposed filter has multiply extended stop bands below and above the passband. Additionally, we provide formulas for computing the filter's frequency response. A comparison between the computed frequency responses for the proposed and conventional filters with the same passband is presented. PMID- 26371930 TI - Paths correlation matrix. AB - Both the Jones and Mueller matrices encounter difficulties when physically modeling mixed materials or rough surfaces due to the complexity of light-matter interactions. To address these issues, we derived a matrix called the paths correlation matrix (PCM), which is a probabilistic mixture of Jones matrices of every light propagation path. Because PCM is related to actual light propagation paths, it is well suited for physical modeling. Experiments were performed, and the reflection PCM of a mixture of polypropylene and graphite was measured. The PCM of the mixed sample was accurately decomposed into pure polypropylene's single reflection, pure graphite's single reflection, and depolarization caused by multiple reflections, which is consistent with the theoretical derivation. Reflection parameters of rough surface can be calculated from PCM decomposition, and the results fit well with the theoretical calculations provided by the Fresnel equations. These theoretical and experimental analyses verify that PCM is an efficient way to physically model light-matter interactions. PMID- 26371931 TI - Frequency-tunable optoelectronic oscillator using a dual-mode amplified feedback laser as an electrically controlled active microwave photonic filter. AB - A widely tunable optoelectronic oscillator (OEO) based on a self-injection-locked monolithic dual-mode amplified feedback laser (DM-AFL) is proposed and experimentally demonstrated. In the proposed OEO structure, the DM-AFL functions as an active tunable microwave photonic filter (MPF). By tuning the injection current applied on the amplifier section of the AFL, tunable microwave outputs ranging from 32 to 41 GHz and single sideband phase noises below -97 dBc/Hz at 10 kHz offset from the carriers were realized. PMID- 26371932 TI - Dielectric laser acceleration of sub-100 keV electrons with silicon dual-pillar grating structures. AB - We present the demonstration of high-gradient laser acceleration and deflection of electrons with silicon dual-pillar grating structures using both evanescent inverse Smith-Purcell modes and coupled modes. Our devices accelerate subrelativistic 86.5 and 96.3 keV electrons by 2.05 keV over 5.6 MUm distance for accelerating gradients of 370 MeV/m with a 3 nJ mode-locked Ti:sapphire laser. We also show that dual pillars can produce uniform accelerating gradients with a coupled-mode field profile. These results represent a significant step toward making practical dielectric laser accelerators for ultrafast, medical, and high energy applications. PMID- 26371933 TI - Diode laser operating on an atomic transition limited by an isotope 87Rb Faraday filter at 780 nm. AB - We demonstrate an extended cavity Faraday laser system using an antireflection coated laser diode as the gain medium and the isotope (87)Rb Faraday anomalous dispersion optical filter (FADOF) as the frequency selective device. Using this method, the laser wavelength works stably at the highest transmission peak of the isotope (87)Rb FADOF over the laser diode current from 55 to 140 mA and the temperature from 15 degrees C to 35 degrees C. Neither the current nor the temperature of the laser diode has significant influence on the output frequency. Compared with previous extended cavity laser systems operating at frequencies irrelevant to spectacular atomic transition lines, the laser system realized here provides a stable laser source with the frequency operating on atomic transitions for many practical applications. PMID- 26371934 TI - Noise-immune cavity-enhanced optical heterodyne molecular spectrometry on N2O 1.283 MUm transition based on a quantum-dot external-cavity diode laser. AB - To access the wavelength within the 1.1-1.3 MUm region, we have developed a quantum-dot (QD) laser with an external-cavity configuration and a linewidth of kilohertz at a 1 ms integration time. The residual electroluminescence, due to the inhomogeneous broadening of the QD gain medium, was observed and filtered out using a grating. While a fiber-coupled electro-optical modulator was employed, this laser system was locked to a high-finesse (F~18,500) optical cavity, and noise-immune cavity-enhanced optical heterodyne molecular spectroscopy was used to observe weak transitions. The Doppler-broadened spectra of a weak N(2)O transition at 1.283 MUm are obtained with a signal-to-noise ratio of 30 for a gas pressure of 54 mTorr. The minimum noise-equivalent absorption coefficient is 5.3*10(-10) cm(-1) Hz(-1/2). This system can be a powerful and stable light source for atomic parity nonconservation measurements using thallium, ytterbium, lead, and iodine. PMID- 26371935 TI - PROUD-based method for simple real-time in-line characterization of propagation induced distortions in NRZ data signals. AB - A simple, in-line method for real-time full characterization (amplitude and phase) of propagation distortions arising because of group velocity dispersion and self-phase modulation on 10-20 Gbps transmitted NRZ optical signals is reported. It is based on phase reconstruction using optical ultrafast differentiation (PROUD), a linear and self-referenced technique. The flexibility of the technique is demonstrated by characterizing different data stream scenarios. Experimental results were modeled using conventional propagation equations, showing good agreement with the measured data. It is envisaged that the proposed method could be used in combination with DSP techniques for the estimation and compensation of propagation distortions in fiber links, not only in conventional IM/DD systems, but also in coherent systems with advanced modulation formats. PMID- 26371936 TI - Watt-level, continuous-wave bismuth-doped all-fiber laser operating at 1.7 MUm. AB - A watt-level all-fiber laser radiating at the wavelength of 1.7 MUm in a continuous-wave regime was developed by using bismuth-doped high-germania optical fiber. A maximum slope efficiency of 33% with respect to the launched pump power was achieved. The dependencies of the slope efficiencies of bismuth-doped fiber laser versus the length of active fiber and reflectivity of the output mirror were obtained. PMID- 26371937 TI - Tunable single-mode coupled-cavity laser in a standard InP photonics platform. AB - We present a wavelength tunable, coupled-cavity laser in a standard indium phosphide multiproject wafer shuttle which did not support distributed feedback gratings. The single-mode operation was enabled by reflections from slots in the laser cavity. The wavelength of the laser emission was tunable over 20 nm near a wavelength of 1560 nm via the currents applied to each section of the laser. A maximum side-mode suppression ratio of 46 dB was observed. The delayed self heterodyne spectrum of the laser showed a Voigt line shape, corresponding to optical linewidths of 3.7 MHz for the Lorentzian and 88 MHz for the Gaussian contributions. PMID- 26371938 TI - Fiber-feedback optical parametric oscillator for half-harmonic generation of sub 100-fs frequency combs around 2 MUm. AB - We demonstrate a femtosecond fiber-feedback optical parametric oscillator (OPO) at degeneracy. The OPO cavity comprises an 80-cm-long fiber composed of a combination of normal and anomalous dispersion sections that provide a net intracavity group delay dispersion close to zero. By using a mode-locked, Yb doped fiber laser as the pump, we achieved half-harmonic generation of 250-MHz, 1.2-nJ nearly transform-limited 97-fs pulses centered at 2090 nm with a total conversion efficiency of 36%. PMID- 26371939 TI - Method for independent and continuous tuning of N lasers phase-locked to the same frequency comb. AB - We present a method of phase locking any number of continuous-wave lasers to an optical frequency comb (OFC) that enables independent frequency positioning and control of each laser while still maintaining lock to the OFC. The scheme employs an acousto-optic modulator (AOM) in a double-pass configuration added to each laser before its light is compared by optical heterodyne with the comb. The only requirement is that the tuning bandwidth of the double-pass AOM setup be larger than half the OFC repetition rate. We demonstrate this scheme and achieve an arbitrary frequency tuning precision, a tuning rate of 200 MHz/s, and a readout precision at the 1 kHz level. PMID- 26371940 TI - Controllable all-fiber orbital angular momentum mode converter. AB - We present a scheme to realize a controllable, scalable, low-cost, and versatile all-fiber orbital angular momentum (OAM) converter. The converter consists of a two-mode fiber (TMF) with its input terminal welded with a single-mode fiber, a mechanical long-period grating (LPG), a mechanical rotator, metal flat slabs, and a fiber polarization controller. The LPG is employed to convert the fundamental fiber mode to higher-order modes and the flat slabs are used to stress the TMF to adjust the relative phase difference between two orthogonal higher-order modes. Selective conversion from the LP(01) mode to the LP(11a), LP(11b), OAM(-1), or OAM(+1) mode is demonstrated in the experiment. PMID- 26371941 TI - Malnutrition in Community-Dwelling Elderly in Turkey: A Multicenter, Cross Sectional Study. AB - BACKGROUND: This study aimed to investigate the prevalence of malnutrition and explore the somatic, psychological, functional, and social or lifestyle characteristics linked to malnutrition in elderly people at a hospital in Turkey. MATERIAL AND METHODS: This study included 1030 patients older than 65 years of age who were seen at the internal medicine and geriatrics outpatient clinics of the study centers in Istanbul, Ankara, Duzce, Corum, Mardin, Malatya, and Diyarbakir provinces between January and December 2014. All patients underwent Mini Nutritional Assessment (MNA) and Geriatric Depression Scale (GDS) tests via one-on-one interview method. The demographic properties of the patients were also recorded during this interview. RESULTS: Among 1030 patients included in this study, 196 (19%) had malnutrition and 300 (29.1%) had malnutrition risk. The malnutrition group and the other groups were significantly different with respect to mean GDS score, income status, educational status, the number of children, functional status (ADL, IADL), the number of patients with depression, and the number of comorbid disorders. According to the results of the logistic regression analysis, age (OR=95% CI: 1.007-1.056; p=0.012), BMI (OR=95% CI: 0.702-0.796; p<0.001), educational status (OR=95% CI: 0.359-0.897; p=0.015), comorbidity (OR=95% CI: 2.296-5.448; p<0.001), and depression score (OR=95% CI: 1.104-3.051; p=0.02) were independently associated with malnutrition. CONCLUSIONS: Our study demonstrates that age, depression, BMI, comorbidity, and the educational status were independently associated with malnutrition in an elderly population. PMID- 26371942 TI - Surgical Reconstruction for Talocalcaneal Coalitions With Severe Hindfoot Valgus Deformity. AB - INTRODUCTION: Coalition resection can restore motion, and improve pain in patients with talocalcaneal coalitions (TCCs) and an aligned foot. However, there is some debate regarding appropriate treatment of patients with associated valgus deformity. The purpose of this study was to present the outcomes and complications following surgical reconstruction, with or without coalition resection, in a series of patients with TCC and severe hindfoot valgus. METHODS: Thirteen consecutive patients (14 feet) were evaluated. Eleven patients were male. Mean age was 14 years. Mean follow-up was 43.8 months. Seven patients (8 feet) underwent simultaneous resection of the coalition and reconstruction, and 6 patients (6 feet) isolated reconstruction. The talar-first metatarsal angle, the talar-horizontal angle, and calcaneal pitch were measured preoperatively and postoperatively. Clinical evaluation was made according to the American Orthopaedic Foot and Ankle Society ankle-hindfoot score. RESULTS: All radiographic values improved significantly and were within the normal ranges postoperatively. The average American Orthopaedic Foot and Ankle Society ankle hindfoot score had improved from 45 to 98 points (P<0.001) in the group of simultaneous resection and reconstruction, and from 60 to 92.3 points (P=0.002) in the group of isolated reconstruction. All patients were asymptomatic at the last follow-up and were satisfied with the procedure. DISCUSSION: Surgical reconstruction with or without coalition resection can achieve significant functional and radiographic improvements, and symptoms relief in selected patients with TCCs and severe valgus deformity. LEVEL OF EVIDENCE: Level IV therapeutic study. PMID- 26371943 TI - Hip Dysplasia in Children With Osteogenesis Imperfecta: Association With Collagen Type I C-Propeptide Mutations. AB - BACKGROUND: Osteogenesis imperfecta (OI) is a heritable skeletal disorder characterized by bone fragility and short stature that is usually due to mutations in 1 of the 2 genes that code for collagen type I alpha-chains. The association between hip dysplasia and OI has not been systematically investigated. In this single-center study, we retrospectively reviewed all cases of OI associated with hip dysplasia to describe clinical characteristics and the effect of therapy. METHODS: We reviewed the charts of 687 patients with OI who were seen at the Shriners Hospital for Children in Montreal between 1999 and 2013 to identify patients with a diagnosis of hip dysplasia. Clinical characteristics and the course after therapeutic interventions were extracted from the charts. RESULTS: Hip dysplasia was diagnosed in 8 hips of 5 patients (4 boys, 1 girl; age at diagnosis ranged between 3 wk and 27 mo old). The prevalence of hip dysplasia and OI was therefore 0.87% (per patient). In 4 of the 5 patients (80%), OI was caused by mutations affecting the C-propeptide of collagen type I, which is otherwise rare in OI. Among the 26 patients with C-propeptide mutations followed at our institution, 4 (15%) had hip dysplasia. Pavlik harness treatment was attempted in 2 patients (3 hips) but was not effective in either case and resulted in avascular necrosis of 1 hip. Femoral varus derotational shortening osteotomies using a telescopic rod were performed in all 8 hips along with a closed reduction in 4 hips and an open reduction in 4 hips. Concomitant pelvic osteotomies were performed in 2 hips (1 patient). Surgery resulted in redislocation of 1 hip; all other surgically treated hips remained reduced. CONCLUSIONS: Clinical screening for hip dysplasia is difficult in OI owing to the bowing of the proximal femur and the risk of causing fractures. OI patients with positive C-propeptide mutation should therefore be screened for hip dysplasia by use of ultrasound. Presence of a C-propeptide mutation appears to be a risk factor for hip dysplasia (80%). It appears that Pavlik harness treatment is not useful in children with OI. The usual treatment of children with OI who pull to stand or started walking with femoral deformity is femoral osteotomy and rodding. In case of associated hip dysplasia with a dislocation, open reduction of the hip and a possible concomitant pelvic osteotomy appears to be a valid management option. LEVEL OF EVIDENCE: Level IV. PMID- 26371944 TI - Transcranial Doppler ultrasound in children with stroke and cerebrovascular disorders. AB - PURPOSE OF REVIEW: A major advantage of transcranial Doppler (TCD) ultrasound is its ability to measure cerebral hemodynamics noninvasively at the patient's bedside. This article summarizes the basic physics and variables used during TCD, recent pediatric data published on the use of TCD in stroke and cerebrovascular disorders and how it may impact diagnosis and management, and some issues to be resolved so that TCD can be put into clinical practice. RECENT FINDINGS: In sickle cell disease in children, TCD is the gold standard stroke prediction tool. Recent data suggest that TCD may provide important information in ischemic stroke because of other childhood arteriopathies such as moyamoya syndrome, transient or focal cerebral arteriopathy, and genetic/syndromic causes. TCD may also detect cerebral emboli and diagnose right-to-left atrial cardiac shunts in children with cryptogenic stroke and transient ischemic attack. SUMMARY: There are many potential clinical applications for TCD in pediatric stroke and cerebrovascular disorders. Additional research in children is needed to determine whether TCD can identify markers of increased stroke risk, elucidate underlying stroke mechanisms, influence the choice of additional testing and treatment, and ultimately impact patient outcomes. PMID- 26371945 TI - Genetic research in autism spectrum disorders. AB - PURPOSE OF REVIEW: The recent explosion of genetic findings in autism spectrum disorder (ASD) research has improved knowledge of the disorder's underlying biology and etiologic architecture. This review introduces concepts and results from recent genetic studies and discusses the manner in which those findings can influence the trajectory of ASD research. RECENT FINDINGS: Large consortium studies have associated ASDs with many types of genetic risk factors, including common polygenic risk, de novo single nucleotide variants, copy number variants, and rare inherited variants. In aggregate, these results confirm the heterogeneity and complexity of ASDs. The rare variant findings in particular point to genes and pathways that begin to bridge the gap between behavior and biology. SUMMARY: Genetic studies have the potential to identify the biological underpinnings of ASDs and other neuropsychiatric disorders. The data they generate are already being used to examine disease pathways and pathogenesis. The results also speak to ASD heterogeneity and, in the future, may be used to stratify research studies and treatment trials. PMID- 26371946 TI - Genetics of inherited arrhythmias in pediatrics. AB - PURPOSE OF REVIEW: Recent international expert consensus statements have updated the clinical and genetic diagnoses of patients suffering from arrhythmogenic diseases. However, a lack of genotype-phenotype correlations has hampered the development of a risk stratification scale for sudden cardiac death. RECENT FINDINGS: The improvement in the field of genetics has prompted the discovery of new genes associated with sudden cardiac death. Sudden cardiac death is a socially devastating event, especially when it occurs in the pediatric population. Physical activity can often trigger the arrhythmia and sudden death may be the first symptom. These inherited cardiac diseases may be difficult to diagnose, leaving family members also at risk. Thanks to the development of new high-throughput technologies, genetics may be used in the diagnosis of these diseases and even cases that remain unexplained after a comprehensive autopsy. Genetic testing cannot only identify the causative genetic variant in the index case, but it enables the detection of relatives at risk of sudden death, despite remaining clinically asymptomatic. SUMMARY: We review the recent advances in the genetics of inherited arrhythmias associated with sudden cardiac death. We focus on the pediatric population, the main group of people suffering from lethal inherited arrhythmias. PMID- 26371947 TI - Azacitidine-Induced Interstitial Pneumonitis. AB - Azacitidine is a demethylating and cytotoxic drug for the treatment of adult patients with (1) myelodysplastic syndromes, (2) chronic myelomonocytic leukemia, and (3) acute myeloid leukemia who are not eligible for induction treatment or hematopoietic stem cell transplantation. Widely described in the literature, the main adverse events are hematotoxicity, digestive toxicity, asthenia, cutaneous toxicity, and infections such as neutropenic sepsis and pneumonia. The pivotal phase III comparative and supporting studies did not point out interstitial pneumonitis as a significant adverse event. Rare clinical data from literature report interstitial lung disease secondary to azacitidine administration, which should therefore be considered as a serious potential adverse event. We, herein, report a case of an 86-year-old white woman with acute myeloid leukemia and azacitidine-induced interstitial pneumonitis. PMID- 26371948 TI - mTOR Complexes Repress Hypertrophic Agonist-Stimulated Expression of Connective Tissue Growth Factor in Adult Cardiac Muscle Cells. AB - Connective tissue growth factor (CTGF) is a fibrogenic cytokine that promotes fibrosis in various organs. In the heart, both cardiomyocytes (CM) and cardiac fibroblasts have been reported as a source of CTGF expression, aiding cardiac fibrosis. Although the mammalian target of rapamycin (mTOR) forms 2 distinct complexes, mTORC1 and mTORC2, and plays a central role in integrating biochemical signals for protein synthesis and cellular homeostasis, we explored its role in CTGF expression in adult feline CM. CM were stimulated with 10 MUM phenylephrine (PE), 200 nM angiotensin (Ang), or 100 nM insulin for 24 hours. PE and Ang, but not insulin, caused an increase in CTGF mRNA expression with the highest expression observed with PE. Inhibition of mTOR with torin1 but not rapamycin significantly enhanced PE-stimulated CTGF expression. Furthermore, silencing of raptor and rictor using shRNA adenoviral vectors to suppress mTORC1 and mTORC2, respectively, or blocking phosphatidylinositol 3-kinase (PI3K) signaling with LY294002 (LY) or Akt signaling by dominant-negative Akt expression caused a substantial increase in PE-stimulated CTGF expression as measured by both mRNA and secreted protein levels. However, studies with dominant-negative delta isoform of protein kinase C demonstrate that delta isoform of protein kinase C is required for both agonist-induced CTGF expression and mTORC2/Akt-mediated CTGF suppression. Finally, PE-stimulated CTGF expression was accompanied with a corresponding increase in Smad3 phosphorylation and pretreatment of cells with SIS3, a Smad3 specific inhibitor, partially blocked the PE-stimulated CTGF expression. Therefore, a PI3K/mTOR/Akt axis plays a suppressive role on agonist stimulated CTGF expression where the loss of this mechanism could be a contributing factor for the onset of cardiac fibrosis in the hypertrophying myocardium. PMID- 26371949 TI - Morphological Identification of TRPC7 in Cardiomyocytes From Normal and Renovascular Hypertensive Rats. AB - OBJECTIVE: We aimed to investigate the expression characteristics of transient receptor potential canonical 7 (TRPC7) in normal and hypertrophic cardiac myocytes. METHODS: The 2-kidney 1-clip (2K1C) method was used to induce renovascular hypertension. Losartan, the potent inhibitor of angiotensin II (Ang II) receptor, was applied to the drinking water of 2K1C rats to inhibit Ang II mediated responses. TRPC7 expression was examined by immunohisto/cytochemistry and Western blot analyses in normal and hypertrophic hearts. The expression level of protein kinase C (PKC), a negative regulator of TRPC7 channel in in vitro study, was also evaluated. RESULTS: In normal rat ventricles, strong TRPC7 immunoreactivity was distributed in the surface sarcolemma of cardiomyocytes, and a moderate but striated TRPC7 immunoreactivity was also detected in the subcellular regions. The 2K1C operation caused significant hypertension and cardiac hypertrophy as demonstrated by respective biophysical or biochemical assays. At this stage, expression of TRPC7 was significantly downregulated at both tissue and cell levels, whereas that of PKC was upregulated. Further analysis revealed a negative correlation between TRPC7 and PKC expression patterns. Oral application of losartan ameliorated the extent of experimentally induced hypertension and cardiac hypertrophy. Simultaneously, it effectively reversed the downregulation of TRPC7 and mildly antagonized the upregulation of PKC. CONCLUSIONS: Taken together, these results for the first time show that TRPC7 localizes in the surface and tubular sarcolemma of cardiomyocytes in normal adult rats and its expression significantly decreases in hypertrophied cardiomyocytes from renovascular hypertensive rats. TRPC7 may thus play a significant role in normal physiological settings in the heart. PMID- 26371950 TI - Intravenous Treatment With Coenzyme Q10 Improves Neurological Outcome and Reduces Infarct Volume After Transient Focal Brain Ischemia in Rats. AB - Coenzyme Q10 (CoQ10) crosses the blood-brain barrier when administered intravenously and accumulates in the brain. In this study, we investigated whether CoQ10 protects against ischemia-reperfusion injury by measuring neurological function and brain infarct volumes in a rat model of transient focal cerebral ischemia. In male Wistar rats, we performed transient middle cerebral artery occlusion (tMCAO) for 60 minutes, followed by reperfusion for 24 hours or 7 days. Forty-five minutes after the onset of occlusion (or 15 minutes before reperfusion), rats received a single intravenous injection of solubilized CoQ10 (30 mg.mL(-1).kg(-1)) or saline (2 mL/kg). Sensory and motor function scores and body weights were obtained before the rats were killed by decapitation, and brain infarct volumes were calculated using tetrazolium chloride staining. CoQ10 brain levels were measured by high-performance liquid chromatography with electrochemical detection. CoQ10 significantly improved neurological behavior and reduced weight loss up to 7 days after tMCAO (P < 0.05). Furthermore, CoQ10 reduced cerebral infarct volumes by 67% at 24 hours after tMCAO and 35% at 7 days (P < 0.05). Cerebral ischemia resulted in a significant reduction in endogenous CoQ10 in both hemispheres (P < 0.05). However, intravenous injection of solubilized CoQ10 resulted in its increase in both hemispheres at 24 hours and in the contralateral hemisphere at 7 days (P < 0.05). Our results demonstrate that CoQ10 is a robust neuroprotective agent against ischemia-reperfusion brain injury in rats, improving both functional and morphological indices of brain damage. PMID- 26371951 TI - Innovative Therapeutics for Atrial Fibrillation: Imminent Breakthroughs or Much Ado About Nothing? PMID- 26371952 TI - Outcomes and complications in superior semicircular canal dehiscence surgery: A systematic review. AB - OBJECTIVE: Superior semicircular canal dehiscence (SSCD) represents a rare condition that may be associated to some particular symptoms as vertigo, autophony, and Tullio phenomenon. In those patients who present severe symptoms surgical treatment is required. Middle fossa craniotomy and transmastoid approaches are both described. Concerning repairing techniques, plugging and/or resurfacing are typically used to close the defect. Our aim was first to analyze the overall outcomes and complications of this surgery. Our second aim was to make a comparison between the different surgical modalities to investigate the eventual advantages and disadvantages. REVIEW METHODS: A search through Ovid MEDLINE was organized in January 2015 to include all eligible articles. A statistical analysis of the obtained data was performed. RESULTS: Twenty studies comprising a total of 150 procedures were included. Four modalities of canal repair were described (plugging, capping, resurfacing, plugging with resurfacing). The overall rate of success resulted in 94% (95% confidence interval: 87%-97%). No statistically significant differences were observed among the different modalities of canal repair concerning both success rate and surgical complications. Differences observed between the middle fossa approach and transmastoid approach in terms of outcome were not statistically significant. CONCLUSIONS: This review showed that surgical treatment for SSCD represents a safe option for those patients with severe symptoms of this condition. Differences observed in terms of success rate or complications were analyzed between the different surgical techniques with results that were not statistically significant. LEVEL OF EVIDENCE: NA Laryngoscope, 126:1218-1224, 2016. PMID- 26371953 TI - Alternaria and Cladosporium calendar of Western Thrace: Relationship with allergic rhinitis symptoms. AB - OBJECTIVES/HYPOTHESIS: Alternaria and Cladosporium are the most important outdoor moulds. The aim of this study was to present fungal spore monitoring data, investigate the relationship of fungal counts with climate conditions, and to explore the clinical significance of Alternaria and Cladosporium species monitoring in allergic rhinitis (AR). STUDY DESIGN: Analytic observational study. METHODS: A 7-day volumetric trap was used to collect circulating Alternaria and Cladosporium fungi. Sixty-nine AR patients were studied and recorded their symptoms by Total 5 Symptoms Score (T5SS). Sensitization prevalence to fungi species was detected by skin prick tests. Monitoring data were correlated to climate conditions and patients symptoms score. RESULTS: Alternaria and Cladosporium were detected throughout the calendar year in ranges of 0 to 217 spores/m(3) and 6.5 to 1,600 spores/m(3) per day, respectively. Highest daily concentrations of both fungi were detected during the summer (73.9 +/- 34.4 spores/m(3) for Alternaria and 595.8 +/- 288.0 spores/m(3) for Cladosporium) and lowest during the winter (2.4 +/- 3.0 spores/m(3) for Alternaria and 24.3 +/- 15.7 spores/m(3) for Cladosporium). Both were positively correlated to mean daily temperature and negatively to relative humidity (all P < 0.001). Clinically, a strong significant correlation between T5SS and airborne fungi levels, both for Alternaria (r = 0.822, P = 0.001) and Cladosporium (r = 0.787, P = 0.002) species was observed. CONCLUSIONS: We found Cladosporium to be the most frequently detected airborne mould, whereas Alternaria was the most prevalent with regard to sensitization rate. Patients' symptoms score was significantly correlated to spore concentrations. Both fungi were clearly affected by climate factors, such as temperature and relative humidity. These findings are important in AR management. LEVEL OF EVIDENCE: N/A. PMID- 26371954 TI - Complete Edentulism and Comorbid Diseases: An Update. AB - The relationship between complete edentulism, which is the terminal outcome of a multifactorial oral disease process and other comorbid diseases, was first reported in 2009. Although the relationship between edentulism and a multitude of systemic diseases was reported, none of the publications studied could determine causality of tooth loss on the incidence of any comorbid disease. Since that publication, there has been a renewed interest in this relationship, and a plethora of new articles have been published. This article will provide an update on articles published since 2008 on the relationship between edentulism and comorbid diseases, and will include the relationship between complete edentulism and such comorbid conditions as malnutrition, obesity, cardiovascular disease, rheumatoid arthritis, pulmonary diseases (including chronic obstructive pulmonary disease), cancer, and even mortality. PMID- 26371955 TI - Solvothermal Synthesis of Three-Dimensional Hierarchical CuS Microspheres from a Cu-Based Ionic Liquid Precursor for High-Performance Asymmetric Supercapacitors. AB - It is meaningful to exploit copper sulfide materials with desired structure as well as potential application due to their cheapness and low toxicity. A low temperature and facile solvothermal method for preparing three-dimensional (3D) hierarchical covellite (CuS) microspheres from an ionic liquid precursor [Bmim]2Cu2Cl6 (Bmim = 1-butyl-3-methylimidazolium) is reported. The formation of CuS nanostructures was achieved by decomposition of intermediate complex Cu(Tu)3Cl (thiourea = Tu), which produced CuS microspheres with diameters of 2.5 4 MUm assembled by nanosheets with thicknesses of 10-15 nm. The ionic liquid, as an "all-in-one" medium, played a key role for the fabrication and self-assembly of CuS nanosheets. The alkylimidazolium rings ([Bmim](+)) were found to adsorb onto the (001) facets of CuS crystals, which inhibited the crystal growth along the [001] direction, while the alkyl chain had influence on the assembly of CuS nanosheets. The CuS microspheres showed enhanced electrochemical performance and high stability for the application in supercapacitors due to intriguing structural design and large specific surface area. When this well-defined CuS electrode was assembled into an asymmetric supercapacitor (ASC) with an activated carbon (AC) electrode, the CuS//AC-ASC demonstrated good cycle performance (~88% capacitance after 4000 cycles) and high energy density (15.06 W h kg(-1) at a power density of 392.9 W kg(-1)). This work provides new insights into the use of copper sulfide electrode materials for asymmetric supercapacitors and other electrochemical devices. PMID- 26371957 TI - Erratum. PMID- 26371956 TI - Synthesis and characterization of a self-fluorescent hyaluronic acid-based gel for dermal applications. AB - Combinations of polymer conjugates affording in situ gelation hold promise for treatment of pathological cavities (e.g., arthritis) and sustained drug release. In particular, hyaluronic acid (HA) functionalized with reactive groups is regarded as an excellent biomaterial due to its tunable cross-linking kinetics and mechanical properties. HA-based reagents, however, can be irritating to surrounding tissues due to the reactivity of pendant groups, and their fast gelation kinetics can result in poor cavity filling. In this study, a biocompatible "click" reaction between cyanobenzothiazole (CBT) and d-cysteine (d Cys) is employed to produce HA-based conjugates for in situ gelation. Rheological studies conducted on a gel obtained from the combination of HA-CBT and HA-d-Cys indicate optimal gelation time and mechanical properties. Further, in vitro studies on porcine skin demonstrate the ability of the gel to form in situ upon subcutaneous injection or topical application, and to act as a reservoir for sustained release of protein therapeutics. Finally, the safety of the HA-based conjugates is demonstrated on human keratinocytes. The presented results demonstrate the applicability of the binary mixture for in situ gelation and the potential of the proposed system for a variety of biomedical applications. PMID- 26371960 TI - Enantiospecific C-H Activation Using Ruthenium Nanocatalysts. AB - The activation of C-H bonds has revolutionized modern synthetic chemistry. However, no general strategy for enantiospecific C-H activation has been developed to date. We herein report an enantiospecific C-H activation reaction followed by deuterium incorporation at stereogenic centers. Mechanistic studies suggest that the selectivity for the alpha-position of the directing heteroatom results from a four-membered dimetallacycle as the key intermediate. This work paves the way to novel molecular chemistry on nanoparticles. PMID- 26371963 TI - Clinical science and biomarkers: against RDoC. PMID- 26371961 TI - Practical Electrochemical Anodic Oxidation of Polycyclic Lactams for Late Stage Functionalization. AB - Electrochemistry provides a powerful tool for the late-stage functionalization of complex lactams. A two-stage protocol for converting lactams, many of which can be prepared through the intramolecular Schmidt reaction of keto azides, is presented. In the first step, anodic oxidation in MeOH using a repurposed power source provides a convenient route to lactams bearing a methoxy group adjacent to nitrogen. Treatment of these intermediates with a Lewis acid in dichloromethane permits the regeneration of a reactive acyliminium ion that is then reacted with a range of nucleophilic species. PMID- 26371964 TI - Enantioselective Total Synthesis of (-)-Incarviatone A. AB - We report herein the first total synthesis of (-)-incarviatone A (1) in 14 steps starting from commercially available inexpensive phenylacetic acid (9). Our early stage synthesis relies on the scalable and sequential C-H functionalization to rapidly assemble the indanyl dialdehyde framework. Further biomimetic cascade strategy allows us to obtain the natural product in a one-pot operation. We also conduct detailed mechanistic studies and disclose all the possible intermediates and isomers formed during the biomimetic cascade process. PMID- 26371965 TI - Electrospun Superhydrophobic Organic/Inorganic Composite Nanofibrous Membranes for Membrane Distillation. AB - Electrospun superhydrophobic organic/inorganic composite nanofibrous membranes exhibiting excellent direct contact membrane distillation (DCMD) performance were fabricated by a facile route combining the hydrophobization of silica nanoparticles (SiO2 NPs) and colloid electrospinning of the hydrophobic silica/poly(vinylidene fluoride) (PVDF) matrix. Benefiting from the utilization of SiO2 NPs with three different particle sizes, the electrospun nanofibrous membranes (ENMs) were endowed with three different delicate nanofiber morphologies and fiber diameter distribution, high porosity, and superhydrophobic property, which resulted in excellent waterproofing and breathability. Significantly, structural attributes analyses have indicated the major contributing role of fiber diameter distribution on determining the augment of permeate vapor flux through regulating mean flow pore size (MFP). Meanwhile, the extremely high liquid entry pressure of water (LEPw, 2.40 +/- 0.10 bar), robust nanofiber morphology of PVDF immobilized SiO2 NPs, remarkable mechanical properties, thermal stability, and corrosion resistance endowed the as-prepared membranes with prominent desalination capability and stability for long-term MD process. The resultant choreographed PVDF/silica ENMs with optimized MFP presented an outstanding permeate vapor flux of 41.1 kg/(m(2).h) and stable low permeate conductivity (~2.45 MUs/cm) (3.5 wt % NaCl salt feed; DeltaT = 40 degrees C) over a DCMD test period of 24 h without membrane pores wetting detected. This result was better than those of typical commercial PVDF membranes and PVDF and modified PVDF ENMs reported so far, suggesting them as promising alternatives for MD applications. PMID- 26371966 TI - Epitaxial growth of hetero-nanostructures based on ultrathin two-dimensional nanosheets. AB - Ultrathin two-dimensional (2D) nanosheets, such as graphene and MoS2, which are demonstrated to be fundamentally and technologically important in many applications, have emerged as a unique family of nanomaterials in chemistry and material science over the past decade. The single-crystalline nature and ultrathin thickness of these 2D nanosheets make them ideal templates for the epitaxial deposition of nanostructures, which offer many possibilities to engineer microsized 2D p-n hetero-junctions at atomic/nanometer scale. This Perspective aims to provide information on the epitaxial growth of hetero nanostructures based on ultrathin 2D nanosheets. Various methods for the epitaxial growth of nanostructures based on ultrathin 2D nanosheets or in situ growth of lateral or vertical epitaxial 2D semiconductor hetero-nanostructures are introduced. The advantages of these 2D epitaxial hetero-nanostructures for some applications, such as electronics, optoelectronics, and electrocatalysis, are also presented. On the basis of the current status of 2D epitaxial hetero nanostructures, the future prospects of this promising area are discussed. PMID- 26371967 TI - Zn-dopant dependent defect evolution in GaN nanowires. AB - Zn doped GaN nanowires with different doping levels (0, <1 at%, and 3-5 at%) have been synthesized through a chemical vapor deposition (CVD) process. The effect of Zn doping on the defect evolution, including stacking fault, dislocation, twin boundary and phase boundary, has been systematically investigated by transmission electron microscopy and first-principles calculations. Undoped GaN nanowires show a hexagonal wurtzite (WZ) structure with good crystallinity. Several kinds of twin boundaries, including (101-3), (101-1) and (202-1), as well as Type I stacking faults (...ABABCBCB...), are observed in the nanowires. The increasing Zn doping level (<1 at%) induces the formation of screw dislocations featuring a predominant screw component along the radial direction of the GaN nanowires. At high Zn doping level (3-5 at%), meta-stable cubic zinc blende (ZB) domains are generated in the WZ GaN nanowires. The WZ/ZB phase boundary (...ABABACBA...) can be identified as Type II stacking faults. The density of stacking faults (both Type I and Type II) increases with increasing the Zn doping levels, which in turn leads to a rough-surface morphology in the GaN nanowires. First-principles calculations reveal that Zn doping will reduce the formation energy of both Type I and Type II stacking faults, favoring their nucleation in GaN nanowires. An understanding of the effect of Zn doping on the defect evolution provides an important method to control the microstructure and the electrical properties of p type GaN nanowires. PMID- 26371968 TI - B11(-): a moving subnanoscale tank tread. AB - We present a concept that an elongated, planar boron cluster can serve as a "tank tread" at the sub-nanometer scale, a novel propulsion system for potential nanomachines. Density functional calculations at the PBE0/6-311+G* level for the global-minimum B11(-)C2v ((1)A1) and B11C2v ((2)B2) structures along the soft in plane rotational mode allow the identification of their corresponding B11(-)C2v and B11C2v transition states, with small rotational energy barriers of 0.42 and 0.55 kcal mol(-1), respectively. The energy barriers are refined to 0.35 and 0.60 kcal mol(-1) at the single-point CCSD(T) level, suggesting that the clusters are structurally fluxional at room temperature. Molecular dynamics simulations show that B11(-) and B11 behave exactly like a tank tread, in which the peripheral B9 ring rotates almost freely around the B2 core. A full turn of rotation may be accomplished in around 2 ps. In contrast to molecular wheels or Wankel motors, the peripheral boron atoms in the tank tread behave as a flexible chain gliding around, rather than as a rigid wheel rotation. This finding is beyond imagination, which expands the concepts of molecular wheels and Wankel motors. PMID- 26371969 TI - Organic Carbon/Water and Dissolved Organic Carbon/Water Partitioning of Cyclic Volatile Methylsiloxanes: Measurements and Polyparameter Linear Free Energy Relationships. AB - The sorption of cyclic volatile methyl siloxanes (cVMS) to organic matter has a strong influence on their fate in the aquatic environment. We report new measurements of the partition ratios between freshwater sediment organic carbon and water (KOC) and between Aldrich humic acid dissolved organic carbon and water (KDOC) for three cVMS, and for three polychlorinated biphenyls (PCBs) that were used as reference chemicals. Our measurements were made using a purge-and-trap method that employs benchmark chemicals to calibrate mass transfer at the air/water interface in a fugacity-based multimedia model. The measured log KOC of octamethylcyclotetrasiloxane (D4), decamethylcyclopentasiloxane (D5), and dodecamethylcyclohexasiloxane (D6) were 5.06, 6.12, and 7.07, and log KDOC were 5.05, 6.13, and 6.79. To our knowledge, our measurements for KOC of D6 and KDOC of D4 and D6 are the first reported. Polyparameter linear free energy relationships (PP-LFERs) derived from training sets of empirical data that did not include cVMS generally did not predict our measured partition ratios of cVMS accurately (root-mean-squared-error (RMSE) for logKOC 0.76 and for logKDOC 0.73). We constructed new PP-LFERs that accurately describe partition ratios for the cVMS as well as for other chemicals by including our new measurements in the existing training sets (logKOC RMSEcVMS: 0.09, logKDOC RMSEcVMS: 0.12). The PP LFERs we have developed here should be further evaluated and perhaps recalibrated when experimental data for other siloxanes become available. PMID- 26371970 TI - Unified Description of the Optical Phonon Modes in N-Layer MoTe2. AB - N-layer transition metal dichalcogenides provide a unique platform to investigate the evolution of the physical properties between the bulk (three-dimensional) and monolayer (quasi-two-dimensional) limits. Here, using high-resolution micro-Raman spectroscopy, we report a unified experimental description of the Gamma-point optical phonons in N-layer 2H-molybdenum ditelluride (MoTe2). We observe series of N-dependent low-frequency interlayer shear and breathing modes (below 40 cm( 1), denoted LSM and LBM) and well-defined Davydov splittings of the mid-frequency modes (in the range 100-200 cm(-1), denoted iX and oX), which solely involve displacements of the chalcogen atoms. In contrast, the high-frequency modes (in the range 200-300 cm(-1), denoted iMX and oMX), arising from displacements of both the metal and chalcogen atoms, exhibit considerably reduced splittings. The manifold of phonon modes associated with the in-plane and out-of-plane displacements are quantitatively described by a force constant model, including interactions up to the second nearest neighbor and surface effects as fitting parameters. The splittings for the iX and oX modes observed in N-layer crystals are directly correlated to the corresponding bulk Davydov splittings between the E2u/E1g and B1u/A1g modes, respectively, and provide a measurement of the frequencies of the bulk silent E2u and B1u optical phonon modes. Our analysis could readily be generalized to other layered crystals. PMID- 26371971 TI - Protein-engineered scaffolds for in vitro 3D culture of primary adult intestinal organoids. AB - Though in vitro culture of primary intestinal organoids has gained significant momentum in recent years, little has been done to investigate the impact of microenvironmental cues provided by the encapsulating matrix on the growth and development of these fragile cultures. In this work, the impact of various in vitro culture parameters on primary adult murine organoid formation and growth are analyzed with a focus on matrix properties and geometric culture configuration. The air-liquid interface culture configuration was found to result in enhanced organoid formation relative to a traditional submerged configuration. Additionally, through use of a recombinantly engineered extracellular matrix (eECM), the effects of biochemical and biomechanical cues were independently studied. Decreasing mechanical stiffness and increasing cell adhesivity were found to increase organoid yield. Tuning of eECM properties was used to obtain organoid formation efficiency values identical to those observed in naturally harvested collagen I matrices but within a stiffer construct with improved ease of physical manipulation. Increased ability to remodel the surrounding matrix through mechanical or enzymatic means was also shown to enhance organoid formation. As the engineering and tunability of recombinant matrices is essentially limitless, continued property optimization may result in further improved matrix performance and may help to identify additional microenvironmental cues that directly impact organoid formation, development, differentiation, and functional behavior. Continued culture of primary organoids in recombinant matrices could therefore prove to be largely advantageous in the field of intestinal tissue engineering for applications in regenerative medicine and in vitro tissue mimics. PMID- 26371972 TI - Hospital Employee Willingness to Work during Earthquakes Versus Pandemics. AB - BACKGROUND: Research indicates that licensed health care workers are less willing to work during a pandemic and that the willingness of nonlicensed staff to work has had limited assessment. OBJECTIVE: We sought to assess and compare the willingness to work in all hospital workers during pandemics and earthquakes. METHODS: An online survey was distributed to Missouri hospital employees. Participants were presented with 2 disaster scenarios (pandemic influenza and earthquake); willingness, ability, and barriers to work were measured. T tests compared willingness to work during a pandemic vs. an earthquake. Multivariate linear regression analyses were conducted to describe factors associated with a higher willingness to work. RESULTS: One thousand eight hundred twenty-two employees participated (15% response rate). More willingness to work was reported for an earthquake than a pandemic (93.3% vs. 84.8%; t = 17.1; p < 0.001). Significantly fewer respondents reported the ability to work during a pandemic (83.5%; t = 17.1; p < 0.001) or an earthquake (89.8%; t = 13.3; p < 0.001) compared to their willingness to work. From multivariate linear regression, factors associated with pandemic willingness to work were as follows: 1) no children <=3 years of age; 2) older children; 3) working full-time; 4) less concern for family; 5) less fear of job loss; and 6) vaccine availability. Earthquake willingness factors included: 1) not having children with special needs and 2) not working a different role. CONCLUSION: Improving care for dependent family members, worker protection, cross training, and job importance education may increase willingness to work during disasters. PMID- 26371973 TI - Excruciating Low Back Pain After Strenuous Exertion: Beware of Lumbar Paraspinal Compartment Syndrome. AB - BACKGROUND: Low back pain is extremely common and usually a minor self-limiting condition. Rarely, however, it is a harbinger of serious medical illness. Paraspinal compartment syndrome is a rare condition, but its timely recognition is important to allow adequate treatment. CASE REPORT: A 16-year-old boy presented to the Emergency Department (ED) with severe low back pain, necessitating intravenous opioids. Laboratory results showed severe rhabdomyolysis. Magnetic resonance imaging of the lumbar spine showed diffuse edema and swelling in the paraspinal muscles. Aggressive fluid therapy was started but despite narcotic analgesia the pain persisted and creatine kinase (CK) levels increased. Compartment pressures of the erector spinae were found to be increased. The decision was made to proceed with bilateral paraspinal fasciotomies. Postoperatively, the patient noted immediate pain relief with rapid decrease of CK level. The patient is pain free and resumed running and swimming 3 months after admission in the ED. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Although paraspinal compartment syndrome is a rare condition, its recognition is of paramount importance to allow adequate surgical treatment, preventing muscle necrosis. Although back pain most often has a benign course, a careful history and physical examination in patients presenting with low back pain allows determination of "red flags." Mandatory further diagnostic tests can identify underlying serious illness. PMID- 26371974 TI - Preparing for the Transition to Practice: A Compilation of Advice from Program Directors to Residency Graduates. PMID- 26371975 TI - Are Discrepancies in Waiting Time for Chest Pain at Emergency Departments between African Americans and Whites Improving Over Time? AB - BACKGROUND: One of the Healthy People 2010 goals was to eliminate racial disparities in the U.S health system. To date, we have limited knowledge about the impact of Healthy People on racial disparities at emergency departments (EDs). OBJECTIVE: We sought to investigate whether there has been an improvement in ED waiting time to see a physician for African Americans (AAs) compared to whites with chest pain symptoms that suggest acute coronary syndrome (ACS). METHODS: A retrospective analysis of the National Hospital and Ambulatory Care Survey data from 2004 to 2011 was conducted in adults with visits related to ACS. We compared covariate-adjusted odds ratios for race for each study year and 2011. In addition, adjusted average differences in waiting times (i.e., time to see a physician) for AAs and whites for each study year were compared. RESULTS: A total of 15,438 visits related to ACS symptoms were made during the study period. The waiting time for AAs (median, 33 min) was statistically longer compared to whites (median, 21 min). In addition, the adjusted waiting time for AAs was 30% longer compared to whites (95% confidence interval, 24-36%). Pairwise comparison of adjusted odds ratios between the year 2011 and other years was not significantly different (all p values = 0.32), suggesting no change in the difference in waiting times during the study period. CONCLUSION: Among patients presenting to the ED with symptoms suggesting ACS, AA compared to whites waited longer to receive care. In addition, this difference in waiting time persisted during the study period, even after the implementation of the Healthy People 2010 initiative. Additional research is warranted to investigate the underlying reasons for unequal care offered to AAs at EDs and the implications on disease outcome. PMID- 26371976 TI - Pediatric Surfer's Myelopathy. AB - BACKGROUND: We present the case of the youngest known patient diagnosed with surfer's myelopathy. Surfer's myelopathy is a rare nontraumatic myelopathy. The most likely etiology, presumably, is arterial insufficiency related to spine hyperextension. Symptoms consist of back pain, urinary incontinence or retention, paraplegia, and sensory loss. CASE REPORT: A 7-year-old girl presented with back pain, urinary retention, and lower extremity weakness after doing backbends during a cheerleading practice the day prior to presentation. WHY SHOULD AN EMERGENCY MEDICINE PHYSICIAN BE AWARE OF THIS?: With the trend of children becoming increasingly active in competitive sports at a younger age, surfer's myelopathy is a diagnosis that should be considered when the symptoms are present and the history consists of hyperextending the back. As in our case, a seemingly benign trauma can lead to the diagnosis of surfer's myelopathy. PMID- 26371977 TI - Accuracy of a SET of Screening Parameters Developed for the Diagnosis of Arterial Gas Embolism: The SANDHOG Criteria. AB - BACKGROUND: Arterial gas embolism (AGE) is a major cause of morbidity and mortality in self-contained underwater breathing apparatus (SCUBA) diving and certain medical procedures. There are currently no well-defined criteria to diagnose AGE. Emergency physicians often find themselves facing a decision whether or not a patient with dive-related symptoms has an AGE and needs to be transferred to a hyperbaric facility. OBJECTIVES: The objective of this study was to test the accuracy of diagnostic criteria developed by the San Diego Hyperbaric Oxygen Group (SANDHOG) for the diagnosis of AGE. METHODS: This was a retrospective review of consultations completed by the Hyperbaric Medicine Department (HBO) at the University of California San Diego where the diagnosis of AGE was considered. HBO staff blinded to the purpose of the study identified potential cases of AGE. The criterion standard was the final diagnosis by a panel of HBO specialists also blinded to the purpose of this study. Descriptive statistics and comparisons evaluating SANDHOG criteria compared to the criterion standard were performed. RESULTS: Twenty-six patients were identified for inclusion. Twenty-three of 26 (88%) were SCUBA divers, 2 had intravascular gas injections, and 1 patient had a military training chamber accident. Nineteen of 26 (73%) patients were diagnosed with AGE. A SANDHOG score of 2 had 94.7% sensitivity (95% confidence interval [CI] 71.9-99.7), 85.7% specificity (95% CI 42.0-99.2), positive likelihood ratio of 6.6 (95% CI 1.1-40.8), and negative likelihood ratio of 0.06 (95% CI 0.01-0.43) for AGE. A SANDHOG score <2 had a negative predictive value of 100% for AGE. CONCLUSION: The SANDHOG criteria appear to be reliable in diagnosing AGE. AGE is unlikely with SANDHOG scores <2, whereas SANDHOG scores >=2 resulted in high sensitivity and specificity for AGE. Emergency physicians may find this tool useful in evaluating patients for suspected AGE, and it may assist in determining whether to transfer the patient to a hyperbaric facility. Future studies should be performed to further examine and validate the accuracy and inter-rater reliability of this tool. PMID- 26371978 TI - A Bed-Ridden Man with Sudden-Onset Dyspnea. PMID- 26371979 TI - Quadrantectomy with oxidized regenerated cellulose ("QUORC"): an innovative oncoplastic technique in breast conserving surgery. AB - Oncoplastic surgery of the breast has generated great excitement over the past years and has become an integrated component of the surgical treatment of breast cancer. Oncoplastic procedures (OPP) associate the best surgical oncologic principles to achieve wide tumor-free margins with the best principles of plastic surgery to optimize cosmetic outcomes. Thanks to oncoplastic techniques, the role of breast conserving surgery (BCS) has been extended to include a group of patients who would otherwise require mastectomy to achieve adeguate tumor clearance. However, even with the use of OPP, cosmetic outcomes may result unsatisfying when a large volume of parenchyma has to be removed, particularly in small-medium size breasts. Recently, it has been proposed the use of ORC (Oxidized Regenerated Cellulose) as a reconstructive biomaterial to optimize the aesthetic results after OPP. The aim of this article is to describe the standard pattern of an innovative surgical oncoplastic technique with ORC, that we have called "QUORC" (QUadrantectomy with Oxidized Regenerated Cellulose), to improve cosmetic results and minimize the possible postoperative complications. KEY WORDS: Breast cancer, Cosmetic results, Oncoplastic surgery results, Oxidized regenerated cellulose, QUORC. PMID- 26371980 TI - A novel AMT gene mutation in a newborn with nonketotic hyperglycinemia and early myoclonic encephalopathy. AB - Early myoclonic encephalopathy (EME) presents in neonatal period with erratic or fragmentary myoclonus and a burst-suppression electroencephalography (EEG) pattern. Nonketotic hyperglycinemia (NKH) is the most common metabolic cause of EME and genetic testing confirms the diagnosis of NKH in around 75% of the patients with a clinical diagnosis of NKH. Three genes are known to cause NKH. Here we describe a case of EME caused by NKH in which a new mutation in aminomethyltransferase (AMT) gene has been detected. PMID- 26371981 TI - An unusual presentation of paediatric Listeria meningitis with selective spinal grey matter involvement and acute demyelinating polyneuropathy. AB - BACKGROUND: Paediatric Listeria meningitis is rare, especially in immuno competent children, but associated with significant mortality and morbidity and frequent complications. METHODS: We report an unusual case of Listeria meningitis in a previously healthy 35 month-old girl with selective spinal grey matter involvement and demyelination in neurophysiological studies. Despite adequate antibiotic treatment, the case was initially complicated by ventriculitis, hydrocephalus and tonsillar herniation through the foramen magnum, requiring external ventricular drainage and subsequent ventriculoperitoneal shunt insertion. Paucity of movements, hypotonia, areflexia and bladder dysfunction then became evident. RESULTS: Electromyogram and nerve conduction studies showed acute inflammatory demyelinating polyneuropathy and the patient received intravenous immunoglobulin followed by corticosteroids. MRI scans with contrast revealed extensive whole cord selective grey matter signal changes. She required extensive neurorehabilitation, making gradual (but incomplete) recovery. CONCLUSION: Spinal cord involvement is rare in neuro-listeriosis and there no previous paediatric reports of Listeria-related myelitis or demyelinating polyneuropathy. The mechanism behind these presentations is unclear but an auto immune response to the infection might be considered. PMID- 26371982 TI - Use of a 660-nm Laser to Aid in the Healing of Necrotic Alveolar Mucosa Caused by Extruded Sodium Hypochlorite: A Case Report. AB - The extrusion of sodium hypochlorite through the apical foramen is an accident that can occur during the flushing procedure in endodontic treatment. The symptomatology is immediate and intense, and there is a long period before the tissues return to normal. Low-level laser therapy might be useful as an adjunctive treatment for damaged soft tissues because of its anti-inflammatory and analgesic effects, which may reduce edema and prevent infection. In this clinical case, the accidental leakage of 1% sodium hypochlorite during the preparation of the root canal of a maxillary right central incisor is reported. This leakage caused immediate and intense pain and edema formation and resulted in an extensive necrotic area in the alveolar mucosa adjacent to the root of the treated tooth. The conventional treatment protocol was combined with low-level laser therapy. Clinical and radiographic examinations after 7 months revealed complete repair of the necrotic area with no paresthesia and further indicated the integrity of the apical region of the tooth where the extrusion of sodium hypochlorite occurred. The combination of low-level laser therapy with a conventional treatment protocol in this case of the extrusion of 1% sodium hypochlorite resulted in the healing of the wounds. PMID- 26371983 TI - The contribution of PCSK9 levels to the phenotypic severity of familial hypercholesterolemia is independent of LDL receptor genotype. AB - Autosomal dominant familial hypercholesterolemia (FH) is caused by genetic mutations in the LDL receptor (LDLR), its ligand apolipoprotein (apo) B, or proprotein convertase subtilisin/kexin type 9 (PCSK9). Although PCSK9 levels have been shown to correlate with LDL-cholesterol (LDL-C) levels in FH, the extent to which PCSK9 levels modulate the phenotypic severity of this disease independent of LDLR genotype remains to be clarified. OBJECTIVE: To assess the relationship between LDLR genotype and the plasma levels of PCSK9, LDL-C, and lipoprotein (a) (Lp(a)) in a large cohort of genetically defined FH heterozygotes (HeFH). METHODS: A total of 292 HeFH carrying one of the nine French-Canadian mutations in the LDLR gene were recruited. The cohort included 226 carriers of a negative receptor (NR) mutation and 66 carriers of a defective-receptor (DR) LDLR gene mutation. Fifty-six control subjects, who were matched with the HeFH subjects based on gender and body mass index, were also recruited. RESULTS: PCSK9 levels were higher in the HeFH group than in the control group (317.9+/-107.1 ng/mL vs. 203.3+/-59.8 ng/mL; P<0.0001). The strength of the association between PCSK9 and LDL-C levels was similar among controls (r=0.37; P=0.005) and HeFH (r=0.31; P<0.0001). Furthermore, a multiple linear regression analysis revealed that the positive correlation between PCSK9 and LDL-C levels remained significant after adjusting for LDLR genotype in the HeFH group. CONCLUSION: These results suggested that the contribution of PCSK9 levels to the phenotypic severity in FH heterozygotes is independent of LDLR genotype. PMID- 26371984 TI - Crystalline retinopathy in a 5-year-old girl with primary hyperoxaluria. PMID- 26371985 TI - [Cyclosporine eye drops: A 4-year retrospective study (2009-2013)]. AB - INTRODUCTION: The University Hospitals Paris Centre Pharmacy compounds three concentrations of cyclosporine eye drops: 20mg/mL (=2%); 5mg/mL (=0.5%) and 0.5mg/mL (=0.05%). Cyclosporine A 2% drops were developed in 1995 to prevent the rejection of high-risk cornea transplants after failure of topical steroids. The other concentrations of eye drops were developed for the treatment of various immune or inflammatory diseases of the cornea, conjunctiva and uvea. These eye drops are dispensed with a physician's prescription to hospitalized or ambulatory patients. A retrospective study over 4 years (2009-2013) was conducted to analyze the details of prescription and possible adverse events. MATERIALS AND METHODS: Dispensations made from January 1st, 2009 through December 31st, 2013 were studied, including patient age, dose of cyclosporine and practice location of prescribing physician. We also recorded the indications for cyclosporine eye drops in a sample of ambulatory patients. The analysis of local tolerability and the effect on visual comfort was based on questionnaires sent to the patients on cyclosporine 2% over a period of 2 months. RESULTS: Cyclosporine eye drops prescription grew continuously from 2009 through 2013 for all concentrations. In 2013, 5,859 patients were treated, among which 3,616 patients with topical cyclosporine 2%, 1,681 patients with 0.5%, and 562 patients with 0.05%. In total, this represents 62,621 eye drops. Treated patients ranged from 1 week to 100 years old. Topical 2% cyclosporine is indicated in 61% of cases to prevent high risk corneal graft rejection. Other indications are corneal ulcer (6%), atopic keratoconjunctivitis (5%), vernal keratoconjunctivitis (5%) and herpetic keratitis (4%). Topical 0.5% cyclosporine is prescribed primarily for dry eye syndrome (20%) and to prevent rejection of high-risk corneal transplantation (11%), to treat ocular rosacea (10%), vernal keratoconjunctivitis (10%), atopic keratoconjunctivitis (8%) and Sjogren's syndrome (7%). Topical 0.05% cyclosporine is prescribed primarily for dry eye syndrome resistant to conventional treatment (47%) and Sjogren's syndrome (21%). Local tolerability of topical cyclosporine was evaluated in 388 patients. The majority of patients (63%) did not experience any adverse effects. The main side effects are redness, burning sensation and itching. CONCLUSION: Prescription of various formulations of topical cyclosporine is current practice for surgical indications: rejection of high-risk corneal transplantation; or medical indications: vernal or atopic keratoconjunctivitis and dry eye syndrome. Further prospective randomized studies would be necessary to validate formulations, doses and indications of cyclosporine eye drops. PMID- 26371986 TI - Treating coronary artery disease in patients with a history of cerebrovascular disease. AB - Patients with coronary artery disease and a history of stroke account for as many as one in eight of all patients with coronary artery disease, and they are at higher risk of ischaemic events than patients with 'lone' coronary artery disease. It is therefore tempting to increase the potency of antithrombotic treatment in this patient subset. However, these patients are also at greater risk of intracranial haemorrhage. In recent trials of new antithrombotic agents in acute coronary syndromes, patients with a history of cerebrovascular disease derived no clinical benefit from (and were even harmed by) the potent novel antithrombotic agents, with an increased risk of intracranial haemorrhage. However, this risk did not appear to be uniform: it was higher in patients with a history of stroke than in those with a history of transient ischaemic attack, and appeared to be largely confined to the first year after stroke/transient ischaemic attack. Specific strategies to optimize the benefit/risk ratio of antithrombotic agents in this relatively common patient group should be developed and evaluated. PMID- 26371987 TI - Socioeconomic (SES) differences in language are evident in female infants at 7months of age. AB - BACKGROUND: Language skills, strongly linked to academic success, are known to differ by socioeconomic status (SES), with lower SES individuals performing less well than higher SES. AIMS: To examine the effect of SES on infant language at 7months of age and the relationship between maternal vocabulary skills and infant language function. To determine if the relationships between SES and infant language are mediated by maternal vocabulary skills. STUDY DESIGN: Longitudinal follow-up of healthy term female African American infants born to mothers in two SES groups: Low SES (income-to-needs<=1, no education beyond high school) and Higher SES (Income-to-Needs >1, at least a high school diploma). SUBJECTS: 54 infants tested at 7months of age; 54 mothers tested at infant age 7months. OUTCOME MEASURES: Preschool Language Scale-5 (PLS-5), Vocabulary and Matrix Reasoning subtests of the Wechsler Adult Intelligence Scale-IV. RESULTS: Low SES infants (n=29) performed less well than Higher SES (n=25) on PLS-5 Total Language, Auditory Comprehension, and Expressive Communication (p<=0.012). Maternal Vocabulary subtest scores were lower in Low SES than Higher SES (p=0.002), but not related to infant PLS Language scores (p>=0.17). Maternal vocabulary did not mediate the relationship between SES and infant language skills at age 7months. CONCLUSIONS: In this single sex and race cohort of healthy, term, female infants, lower SES exerted negative effects on infant language by 7months of age. While maternal vocabulary scores showed no relation with infant language skills at 7months, continued study of the relations between SES, infant outcomes and maternal characteristics is needed to determine how low SES conditions impact early language. These findings underscore the importance of early interventions, as well as policies designed to improve socioeconomic conditions for infants and families. PMID- 26371988 TI - Impacts of multiple stressors on ecosystem function: Leaf decomposition in constructed urban wetlands. AB - The impact of stormwater on stream biota is well documented, but less is known about the impacts on ecosystem processes, such as the breakdown of organic matter. This study sought to establish whether the degree of urbanisation affected rates of leaf-litter breakdown within constructed wetlands. A litter bag method was used to ascertain rate of decomposition along a gradient of urbanisation (total imperviousness, TI), in constructed wetlands in western and south-eastern Melbourne. A significant positive relationship between TI and breakdown rate was found in the south-eastern wetlands. The significant reduction in rate of invertebrate-mediated breakdown with increasing concentration of certain metals was consistent with other studies. However, overall there was an increase in rate of breakdown. Studies have shown that the effects of heavy metals can be negated if nutrient levels are high. Our results suggest that other parameters besides exposure to contaminants are likely to affect leaf litter breakdown. PMID- 26371989 TI - Threshold and resilience management of coupled urbanization and water environmental system in the rapidly changing coastal region. AB - The concept of thresholds shows important implications for environmental and resource management. Here we derived potential landscape thresholds which indicated abrupt changes in water quality or the dividing points between exceeding and failing to meet national surface water quality standards for a rapidly urbanizing city on the Eastern Coast in China. The analysis of landscape thresholds was based on regression models linking each of the seven water quality variables to each of the six landscape metrics for this coupled land-water system. We found substantial and accelerating urban sprawl at the suburban areas between 2000 and 2008, and detected significant nonlinear relations between water quality and landscape pattern. This research demonstrated that a simple modeling technique could provide insights on environmental thresholds to support more informed decision making in land use, water environmental and resilience management. PMID- 26371990 TI - Long-term Effects of Vagus Nerve Stimulation in Treatment-resistant Depression: A 5-year Follow up Case Series. PMID- 26371991 TI - Multifunctional hybrid nanogels for theranostic applications. AB - This paper reviews a wide set of theranostic applications based on the special properties associated with composite nanogels. The nanogels presented here are mostly hybridized with quantum dots, magnetic nanoparticles, and plasmonic metal noble nanoparticles. These inorganic components confer nanogels multifunctional properties that extend their applications from drug delivery systems to diagnosis and therapy. Nanogels can also be surface functionalized with specific ligands to achieve targeted therapy and reduce toxicity. This versatility makes hybrid nanogels very promising agents for imaging, diagnosis and treatment of cancer and other diseases. PMID- 26371992 TI - Examining the Association Between School Vending Machines and Children's Body Mass Index by Socioeconomic Status. AB - OBJECTIVE: To examine the association between vending machine availability in schools and body mass index (BMI) among subgroups of children based on gender, race/ethnicity, and socioeconomic status classifications. METHODS: First difference multivariate regressions were estimated using longitudinal fifth- and eighth-grade data from the Early Childhood Longitudinal Study. The specifications were disaggregated by gender, race/ethnicity, and family socioeconomic status classifications. RESULTS: Vending machine availability had a positive association (P < .10) with BMI among Hispanic male children and low-income Hispanic children. Living in an urban location (P < .05) and hours watching television (P < .05) were also positively associated with BMI for these subgroups. Supplemental Nutrition Assistance Program enrollment was negatively associated with BMI for low-income Hispanic students (P < .05). These findings were not statistically significant when using Bonferroni adjusted critical values. CONCLUSIONS AND IMPLICATIONS: The results suggest that the school food environment could reinforce health disparities that exist for Hispanic male children and low-income Hispanic children. PMID- 26371993 TI - Oriented growth and transdifferentiation of mesenchymal stem cells towards a Schwann cell fate on micropatterned substrates. AB - While Schwann cells (SCs) have a significant role in peripheral nerve regeneration, their use in treatments has been limited because of lack of a readily available source. To address this issue, this study focused on the effect of guidance cues by employing micropatterned polymeric films to influence the alignment, morphology and transdifferentiation of bone marrow-derived rat mesenchymal stem cells (MSCs) towards a Schwann cell-like fate. Two different types of polymers, biocompatible polystyrene (PS) and biodegradable poly(lactic acid) (PLA) were used to fabricate patterned films. Percentages of transdifferentiated MSCs (tMSCs) immunolabeled with SC markers (alpha-S100beta and alpha-p75(NTR)) were found to be similar on patterned versus smooth PS and PLA substrates. However, patterning had a significant effect on the alignment and elongation of the tMSCs. More than 80% of the tMSCs were oriented in the direction of microgrooves (0 degrees -20 degrees ), while cells on the smooth substrates were randomly oriented. The aspect ratio [AR, ratio of length (in direction of microgrooves) and breadth (in direction perpendicular to microgrooves)] of the tMSCs on patterned substrates had a value of approximately five, as compared to cells on smooth substrates where the AR was one. Understanding responses to these cues in vitro helps us in understanding the behavior and interaction of the cells with the 3D environment of the scaffolds, facilitating the application of these concepts to designing effective nerve guidance conduits for peripheral nerve regeneration. PMID- 26371995 TI - Craniosynostosis. AB - Craniosynostosis is the premature fusion of one or more of the cranial sutures. About 8% of the patients have familial or syndromic forms of synostosis, and in the remainder it occurs as a spontaneous isolated defect. Familial craniosynostosis syndromes are typically transmitted as an autosomal dominant trait resulting in disruption of the fibroblast growth factor receptor pathway. Familiarity with the characteristic head shapes resulting from craniosynostosis allows bedside diagnosis and differentiation from positional plagiocephaly. Because of the risks associated with untreated craniosynostosis, surgical treatment is usually undertaken soon after diagnosis. Current surgical methods include open calvarial reconstruction, minimally invasive strip craniectomy with use of postoperative molding helmet, minimally invasive strip craniectomy with spring implantation, and cranial distraction. Early referral to a pediatric craniofacial center allows all treatment options to be explored. PMID- 26371994 TI - Right ventricular diastolic function and exercise capacity in COPD. AB - BACKGROUND: Decreased exercise capacity in chronic obstructive pulmonary disease (COPD) is incompletely explained by pulmonary pathologic and physiologic abnormalities. We evaluated the extent to which right ventricular diastolic function (RVDF) is associated with exercise capacity in COPD. METHODS: Fifty-one patients with COPD were evaluated by echocardiography, spirometry, and the 6 min walk test (6MWT). RVDF was assessed using 4 echocardiographic parameters: 1) the ratio of tricuspid valve (TV) early (E) and late (A) inflow velocities (TV E/A) 2) TV early tissue Doppler velocity (TV e') 3) TV deceleration time (DT) and 4) the ratio of TV E and e' velocities (TV E/e'). Multiple linear regression was used to examine the extent to which these parameters were associated with 6MWT distance. All models adjusted for age, sex, post-bronchodilator FEV1/FVC, resting heart rate, and use of supplemental O2 during 6MWT. A regression model was calculated for each of the 4 markers of RVDF. RESULTS: Forty-seven percent of the sample had GOLD stage III or IV COPD. All 51 subjects had preserved left ventricular ejection fraction (LVEF, mean = 71.7%, SD = 7.8%). A higher TV E/A ratio was associated with increased 6MWT distance (p = 0.001). TV e', TV DT and TV E/e' did not have a statistically significant association with 6MWT distance in regression models. CONCLUSIONS: In a cohort with moderate to severe COPD and normal LVEF, TV E/A was associated with 6MWT distance after adjusting for relevant demographic and medical covariates. RV diastolic dysfunction may independently contribute to exercise intolerance in COPD. PMID- 26371996 TI - A Comprehensive Analysis in Terms of Molecule-Intrinsic Quasi-Atomic Orbitals. IV. Bond Breaking and Bond Forming along the Dissociative Reaction Path of Dioxetane. AB - The quantitative analysis of molecular density matrices in terms of oriented quasi-atomic orbitals (QUAOs) is shown to yield detailed conceptual insight into the dissociation of dioxetane on the basis of ab initio wave functions. The QUAOs persist and can be followed throughout the reaction path. The kinetic bond orders and the orbital populations of the QUAOs quantitatively reveal the changes of the bonding interactions along the reaction path. At the transition state the OO bond is broken, and the molecule becomes a biradical. After the transition state the reaction path bifurcates. The minimum energy path gently descends from the transition state via a valley-ridge inflection point to a second saddle point, from which two new minimum energy paths lead to two equivalent formaldehyde dimers. The CC bond breaks, and the pi-bonds of the formaldehyde fragments form in close vicinity of the second saddle point. The changes of the interactions in this region are elucidated by the analysis of the rearrangements of the QUAOs. PMID- 26371998 TI - Informed Consent Challenges in Frail, Delirious, Demented, and Do-Not-Resuscitate Adult Patients. AB - Without informed consent, any invasive procedure becomes an assault. The prevailing legal and ethical standard is that the physician has a fiduciary duty to give enough information to the patient so that a reasonable person can make an informed decision to accept or refuse the proposed treatment. The patient's frailty, delirium and/or dementia, and end-of-life concerns and expectations can make informed consent a difficult task. This review examines informed consent requirements for adults and provides communication tools to enable shared decision making while engendering patient-physician trust. PMID- 26371999 TI - Improving Patient Safety: Implementing Dose Monitoring Software in Fluoroscopically Guided Interventions. AB - PURPOSE: To assess whether dose monitoring software can be successfully implemented in fluoroscopically guided interventions and to provide dose data based on levels of complexity. MATERIALS AND METHODS: After launching the software (DoseWatch; GE Healthcare Systems, Buc, France), data were collected for 6 months and analyzed by means of kerma-area product (KAP; Gy/cm(2)), cumulative air kerma (KA,R; Gy), and fluoroscopic time (minutes). Data analysis was executed by level of complexity as graded by the operators. Complexity grading was based on factors such as tortuosity and calcification of vessel, variant anatomy, and patient cooperation. RESULTS: The software successfully transferred dose data of 357 fluoroscopically guided procedures. KAP was 0.238-400 Gy/cm(2) with mean, median, and 75th percentile values of 46.0 Gy/cm(2), 163.2 Gy/cm(2), and 541.1 Gy/cm(2) (KA,R, 0.013-4.1 Gy; mean, median, 75th percentile, 0.48 Gy, 0.97 Gy, 3.98 Gy). Highest dose values were seen in transarterial chemoembolization (KAP mean, median, 75th percentile, 229.5 Gy/cm(2), 216.4 Gy/cm(2), 299.9 Gy/cm(2); KA,R mean, median, 75th percentile, 1.9 Gy, 1.2 Gy, 1.7 Gy). Analysis revealed that the level of complexity strongly correlated with KAP (r = 0.88; P < .001) whereas there was no direct correlation of KAP and fluoroscopy time. During the same intervention, KA,R and fluoroscopy time increased with level of complexity, but the correlation was not statistically significant. CONCLUSIONS: Implementation of dose monitoring software in fluoroscopically guided interventions can be successfully accomplished, and it facilitates data comparison. PMID- 26372000 TI - Quality Improvement Guidelines for Adult Diagnostic Cervicocerebral Angiography: Update Cooperative Study between the Society of Interventional Radiology (SIR), American Society of Neuroradiology (ASNR), and Society of NeuroInterventional Surgery (SNIS). PMID- 26372001 TI - Visual arts training is linked to flexible attention to local and global levels of visual stimuli. AB - Observational drawing skill has been shown to be associated with the ability to focus on local visual details. It is unclear whether superior performance in local processing is indicative of the ability to attend to, and flexibly switch between, local and global levels of visual stimuli. It is also unknown whether these attentional enhancements remain specific to observational drawing skill or are a product of a wide range of artistic activities. The current study aimed to address these questions by testing if flexible visual processing predicts artistic group membership and observational drawing skill in a sample of first year bachelor's degree art students (n=23) and non-art students (n=23). A pattern of local and global visual processing enhancements was found in relation to artistic group membership and drawing skill, with local processing ability found to be specifically related to individual differences in drawing skill. Enhanced global processing and more fluent switching between local and global levels of hierarchical stimuli predicted both drawing skill and artistic group membership, suggesting that these are beneficial attentional mechanisms for art-making in a range of domains. These findings support a top-down attentional model of artistic expertise and shed light on the domain specific and domain-general attentional enhancements induced by proficiency in the visual arts. PMID- 26372002 TI - Fragile X Mental Retardation Protein and Dendritic Local Translation of the Alpha Subunit of the Calcium/Calmodulin-Dependent Kinase II Messenger RNA Are Required for the Structural Plasticity Underlying Olfactory Learning. AB - BACKGROUND: In the adult brain, structural plasticity allowing gain or loss of synapses remodels circuits to support learning. In fragile X syndrome, the absence of fragile X mental retardation protein (FMRP) leads to defects in plasticity and learning deficits. FMRP is a master regulator of local translation but its implication in learning-induced structural plasticity is unknown. METHODS: Using an olfactory learning task requiring adult-born olfactory bulb neurons and cell-specific ablation of FMRP, we investigated whether learning shapes adult-born neuron morphology during their synaptic integration and its dependence on FMRP. We used alpha subunit of the calcium/calmodulin-dependent kinase II (alphaCaMKII) mutant mice with altered dendritic localization of alphaCaMKII messenger RNA, as well as a reporter of alphaCaMKII local translation to investigate the role of this FMRP messenger RNA target in learning-dependent structural plasticity. RESULTS: Learning induces profound changes in dendritic architecture and spine morphology of adult-born neurons that are prevented by ablation of FMRP in adult-born neurons and rescued by an metabotropic glutamate receptor 5 antagonist. Moreover, dendritically translated alphaCaMKII is necessary for learning and associated structural modifications and learning triggers an FMRP-dependent increase of alphaCaMKII dendritic translation in adult born neurons. CONCLUSIONS: Our results strongly suggest that FMRP mediates structural plasticity of olfactory bulb adult-born neurons to support olfactory learning through alphaCaMKII local translation. This reveals a new role for FMRP regulated dendritic local translation in learning-induced structural plasticity. This might be of clinical relevance for the understanding of critical periods disruption in autism spectrum disorder patients, among which fragile X syndrome is the primary monogenic cause. PMID- 26372003 TI - Increased generalization of learned associations is related to re-experiencing symptoms in veterans with symptoms of post-traumatic stress. AB - One interpretation of re-experiencing symptoms in post-traumatic stress disorder (PTSD) is that memories related to emotional information are stored strongly, but with insufficient specificity, so that stimuli which are minimally related to the traumatic event are sufficient to trigger recall. If so, re-experiencing symptoms may reflect a general bias against encoding background information during a learning experience, and this tendency might not be limited to learning about traumatic or even autobiographical events. To test this possibility, we administered a discrimination-and-transfer task to 60 Veterans (11.2% female, mean age 54.0 years) self-assessed for PTSD symptoms in order to examine whether re-experiencing symptoms were associated with increased generalization following associative learning. The discrimination task involved learning to choose the rewarded object from each of six object pairs; each pair differed in color or shape but not both. In the transfer phase, the irrelevant feature in each pair was altered. Regression analysis revealed no relationships between re experiencing symptoms and initial discrimination learning. However, re experiencing symptom scores contributed to the prediction of transfer performance. Other PTSD symptom clusters (avoidance/numbing, hyperarousal) did not account for significant additional variance. The results are consistent with an emerging interpretation of re-experiencing symptoms as reflecting a learning bias that favors generalization at the expense of specificity. Future studies will be needed to determine whether this learning bias may pre-date and confer risk for, re-experiencing symptoms in individuals subsequently exposed to trauma, or emerges only in the wake of trauma exposure and PTSD symptom development. PMID- 26372004 TI - Patenting strategies, the authentication US fiscal methodology, discovery and development of imidazole-containing peptide compounds with free-radical scavenging and transglycating properties acting as targeted drug regulators and homeostatic agents with diverse therapeutic activities for pharmacy of diabetes and metabolic diseases. AB - INTRODUCTION: Diabetes mellitus is the seventh-leading cause of death in the US and diabetic complications are interlaced with specific diverse microvascular and macrovascular pathologies resulting from hyperglycemia. The society should expand prowess and patenting of biotechnology to cure disease and complications. AREAS COVERED: The work summarizes biological activities of patented carnosine mimetics resistant in formulations to enzymatic hydrolysis with human carnosinases that are acting as a universal form of antioxidant, deglycating and transglycating agents that inhibit sugar-mediated protein crosslinking, chelate or inactivate a number of transition metal ions (including ferrous and copper ions), possess lipid peroxidase type of activity and protection of antioxidant enzymes from inactivation. L-Carnosine released systemically from N-acetylcarnosine lubricant eye drops or from skeletal muscle during exercise is transported into hypothalamic tuberomammillary nucleus-histamine neurons and hydrolyzed. The resulting L-histidine is subsequently converted into histamine acting as metabolic fuel feeding for the hypothalamic histaminergic system. This mechanism is responsible for the effects of L-carnosine on autonomic neurotransmission and physiological function of pancreas, stimulating in vivo regeneration of insulin producing beta cells. EXPERT OPINION: Therapeutic benefits for imidazole containing antioxidants (nutraceutical non-hydrolyzed carnosine, carcinine, D carnosine, ophthalmic prodrug N-acetylcarnosine, leucyl-histidylhydrazide and patented formulations thereof) are an essential part of diabetes treatment. PMID- 26372005 TI - Prospective associations of low positive emotionality with first onsets of depressive and anxiety disorders: Results from a 10-wave latent trait-state modeling study. AB - Unipolar depressive disorders and anxiety disorders co-occur at high rates and can be difficult to distinguish from one another. Cross-sectional evidence has demonstrated that whereas all these disorders are characterized by high negative emotion, low positive emotion shows specificity in its associations with depressive disorders, social anxiety disorder, and possibly generalized anxiety disorder. However, it remains unknown whether low positive emotionality, a personality trait characterized by the tendency to experience low positive emotion over time, prospectively marks risk for the initial development of these disorders. We aimed to help address this gap. Each year for up to 10 waves, participants (n = 627, mean age = 17 years at baseline) completed self-report measures of mood and personality and a structured clinical interview. A latent trait-state decomposition technique was used to model positive emotionality and related personality traits over the first 3 years of the study. Survival analyses were used to test the prospective associations of low positive emotionality with first onsets of disorders over the subsequent 6-year follow-up among participants with no relevant disorder history. The results showed that low positive emotionality was a risk marker for depressive disorders, social anxiety disorder, and generalized anxiety disorder, although evidence for its specificity to these disorders versus the remaining anxiety disorders was inconclusive. Additional analyses revealed that the risk effects were largely accounted for by the overlap of low positive emotionality with neuroticism. The implications for understanding the role of positive emotionality in depressive disorders and anxiety disorders are discussed. PMID- 26372006 TI - The link between nonsuicidal self-injury and acquired capability for suicide: A longitudinal study. AB - Despite recent findings that nonsuicidal self-injury (NSSI) is a strong predictor of suicide attempts, little empirical attention has been given to the mechanism through which NSSI increases suicide risk. The present 2-wave longitudinal study represents the first critical test of Joiner's (2005) hypothesis that NSSI is linked to lower pain sensitivity and fear of death over time (i.e., NSSI leads to acquired capability for suicide). Undergraduate students (N = 782) at a midsized Canadian university completed measures of NSSI and acquired capability for suicide at 2 time points (1 year apart). Path analyses revealed that higher frequency of NSSI engagement in the past year was associated with greater acquired capability for suicide 1 year later, and that this link was unidirectional. This study provides the first longitudinal evidence that a potential mechanism for the link between NSSI and suicide attempts may be acquired capability for suicide, and suggests that targeting NSSI engagement could help to prevent individuals from acquiring the ability to enact more lethal forms of self-injury. PMID- 26372007 TI - Metacognitive impairments in schizophrenia are arrested at extreme levels of psychopathy: The cut-off effect. AB - Psychopathy and metacognitive difficulties have been associated with the occurrence of violence in schizophrenia. However, evidence suggests that nonschizophrenic psychopaths match or even outperform healthy controls on tests of metacognition. We hypothesize that the metacognitive difficulties associated with schizophrenia may be ameliorated by comorbid psychopathy. To this end, metacognition (using the Metacognition Assessment Scale-Abbreviated [MAS-A]) and psychopathy (using the Hare Psychopathy Checklist-Revised [PCL-R]) are assessed in 79 patients with schizophrenia with a history of criminal offending. Piecewise regression reveals that the association between metacognition and psychopathy changes from a negative to a positive association at a breakpoint corresponding to a score of 24 on the PCL-R. This score is within the range of the cut-off point used for the diagnosis of psychopathy in Europe, which corresponds to a score of 26 on the PCL-R. The patients scoring above 24 on the PCL-R demonstrated better overall metacognitive abilities, suggesting that these patients constitute a specific group in which schizophrenia has an attenuated impairing effect on metacognition. However, this effect was absent for the Mastery subscale of the MAS-A, which refers to the ability to use one's own mental states to solve social and psychological dilemmas. Our results suggest that the relative preservation of metacognitive abilities in schizophrenic patients with extreme levels of psychopathy may contribute to their offending behavior as it may enable them to understand how to manipulate and extort their victims. However, enhancing the Mastery domain of metacognition in these patients may attenuate this offending behavior. PMID- 26372009 TI - Aplastic anemia associated with pregnancy: maternal and fetal complications. AB - OBJECTIVE: To analyze obstetric complications associated with aplastic anemia (AA) among pregnant women and analyze the underlying factors. METHODS: A retrospective analysis of 60 pregnancies with AA. Thirty four of these patients were grouped as complicated group having obstetric complications and the rest 26 without complications as the control group. Comparative analysis was conducted to access the related risk factors, which may affect the maternal and fetal complications. RESULTS: The major maternal complications in this study were premature labor, gestational diabetes, pre-eclampsia, acute heart failure, postpartum hemorrhage, and severe postpartum infection. Premature birth, fetal growth restriction and stillbirths accounted for 27.3%, 5.0% and 6.7% of prenatal mortality. Twenty six of patients had uncomplicated pregnancies. Patients without complications had higher mean hemoglobin concentration (75.38 +/- 16.19 g/L) and platelet counts (23.92 +/- 14.82 * 10(9) cells/L) than did women with complications (mean hemoglobin concentration, 61.47 +/- 15.15 g/L, p = 0.001; mean platelet counts, 12.11 +/- 7.87 * 10(9) cells/L, p < 0.001). CONCLUSION: Pregnancies associated with AA can carry the risk of multiple maternal and fetal complications. Low hemoglobin concentration and platelet counts may be the primary risk factors for obstetric complications in pregnancies associated with AA. PMID- 26372008 TI - Hepatitis C Infection Among Hispanics in California. AB - Hispanics in California are more likely to be infected with hepatitis C, and those infected have had their infection detected later. A total of 1,567 Hispanic and Caucasian individuals were tested for antibodies to hepatitis C from 2000 through 2013. Interviewers administered the Risk Behavior Assessment. Hepatitis C infected Hispanics were incarcerated longer than hepatitis C-infected Caucasians, and they used marijuana less and illicit methadone more. They were more likely to use crack, heroin, speedballs, and to have been in methadone treatment. Hispanics need hepatitis C testing linked to methadone treatment and written information in Spanish and English. PMID- 26372010 TI - Syndromic Approach to Arboviral Diagnostics for Global Travelers as a Basis for Infectious Disease Surveillance. AB - BACKGROUND: Arboviruses have overlapping geographical distributions and can cause symptoms that coincide with more common infections. Therefore, arbovirus infections are often neglected by travel diagnostics. Here, we assessed the potential of syndrome-based approaches for diagnosis and surveillance of neglected arboviral diseases in returning travelers. METHOD: To map the patients high at risk of missed clinical arboviral infections we compared the quantity of all arboviral diagnostic requests by physicians in the Netherlands, from 2009 through 2013, with a literature-based assessment of the travelers' likely exposure to an arbovirus. RESULTS: 2153 patients, with travel and clinical history were evaluated. The diagnostic assay for dengue virus (DENV) was the most commonly requested (86%). Of travelers returning from Southeast Asia with symptoms compatible with chikungunya virus (CHIKV), only 55% were tested. For travelers in Europe, arbovirus diagnostics were rarely requested. Over all, diagnostics for most arboviruses were requested only on severe clinical presentation. CONCLUSION: Travel destination and syndrome were used inconsistently for triage of diagnostics, likely resulting in vast under diagnosis of arboviral infections of public health significance. This study shows the need for more awareness among physicians and standardization of syndromic diagnostic algorithms. PMID- 26372011 TI - Environmental Persistence of Bacillus anthracis and Bacillus subtilis Spores. AB - There is a lack of data for how the viability of biological agents may degrade over time in different environments. In this study, experiments were conducted to determine the persistence of Bacillus anthracis and Bacillus subtilis spores on outdoor materials with and without exposure to simulated sunlight, using ultraviolet (UV)-A/B radiation. Spores were inoculated onto glass, wood, concrete, and topsoil and recovered after periods of 2, 14, 28, and 56 days. Recovery and inactivation kinetics for the two species were assessed for each surface material and UV exposure condition. Results suggest that with exposure to UV, decay of spore viability for both Bacillus species occurs in two phases, with an initial rapid decay, followed by a slower inactivation period. The exception was with topsoil, in which there was minimal loss of spore viability in soil over 56 days, with or without UV exposure. The greatest loss in viable spore recovery occurred on glass with UV exposure, with nearly a four log10 reduction after just two days. In most cases, B. subtilis had a slower rate of decay than B. anthracis, although less B. subtilis was recovered initially. PMID- 26372012 TI - Adult Behavior in Male Mice Exposed to E-Cigarette Nicotine Vapors during Late Prenatal and Early Postnatal Life. AB - METHODS: Timed-pregnant C57BL/6J mice were exposed to 2.4% nicotine in propylene glycol (PG) or 0% nicotine /PG once a day from gestational day 15 until delivery. After delivery, offspring and mothers were exposed to E-cigarette vapors for an additional 14 days from postnatal day 2 through 16. Following their last exposure serum cotinine levels were measured in female juvenile mice. Male mice underwent behavioral testing at 14 weeks of age to assess sensorimotor, affective, and cognitive functional domains. RESULTS: Adult male mice exposed to 2.4% nicotine/PG E-cigarette vapors had significantly more head dips in the zero maze test and higher levels of rearing activity in the open field test compared to 0% nicotine/PG exposed mice and untreated controls. In the water maze test after reversal training, the 2.4% nicotine/PG mice spent more than 25% of time in the new location whereas the other groups did not. CONCLUSION: Adult male mice exhibited increased levels of activity in the zero maze and open field tests when exposed to E-cigarette vapor containing nicotine during late prenatal and early postnatal life. These findings indicate that nicotine exposure from E-cigarettes may cause persistent behavioral changes when exposure occurs during a period of rapid brain growth. PMID- 26372013 TI - Bacterial Diversity and Community Structure in the Pine Wood Nematode Bursaphelenchus xylophilus and B. mucronatus with Different Virulence by High Throughput Sequencing of the 16S rDNA. AB - Bursaphelenchus xylophilus is the pathogen of pine wilt disease. Bursaphelenchus mucronatus is similar to B. xylophilus in morphology. Both species share a common niche, but they are quite different in pathogenicity. Presently, the role of bacteria in pine wilt disease development has been widely speculated. The diversity of bacteria associated with B. xylophilus and B. mucronatus with different virulence remains unclear. In this study, virulence of four B. xylophilus and four B. mucronatus strains were evaluated by inoculating Pinus thunbergii. High-throughput sequencing targeted 16S rDNA of different virulence nematode strains was carried out. The associated bacterial community structures of the eight strains were analyzed. The results showed that 634,051 high-quality sequences were obtained from the eight nematode strains. The number of OTUs of bacteria associated with B. mucronatus was generally greater than those of B. xylophilus. The richness of the community of bacteria associated with high virulent B. xylophilus ZL1 and AmA3 was higher than moderately virulent B. xylophilus AA3, HE2, and all B. mucronatus strains. While the diversity of bacteria associated with B. mucronatus was higher than B. xylophilus. Stenotrophomonas, Pseudomonadaceae_Unclassified or Rhizobiaceae_Unclassified were predominant in the nematode strains with different virulence. Oxalobacteraceae and Achromobacter were found more abundant in the low virulent B. xylophilus and non-virulent B. mucronatus strains. PMID- 26372014 TI - Cultural Differences in Donation Decision-Making. AB - Decisions to help those in need are essential for human development and survival. Previous studies have demonstrated the "identified effect", in which one identifiable individual typically invokes stronger feelings of compassion and receives greater aid than statistical victim. However, this preference might be influenced by cultural differences. In the current study, Chinese respondents' ratings of distress and sympathy and their willingness to contribute are greater for a group of sick children than an individual. In the U.S., greater willingness to help and sympathy are elicited by an identified victim in comparison with an unidentified one. The different results may demonstrate the importance of cultural differences when trying to understand people's prosocial behavior. PMID- 26372015 TI - Bayesian accounts and black swans: Questioning the erotetic theory of delusional thinking. AB - Parrott and Koralus argue that a particular cognitive factor--"impaired endogenous question raising"--offers a parsimonious account of three delusion related phenomena: (1) the development of the Capgras delusion; (2) evidence that patients with schizophrenia outperform healthy control participants on a conditional reasoning task; and (3) evidence that deluded individuals "jump to conclusions". In this response, I assess these claims, and raise my own questions about the "erotetic" theory of delusional thinking. PMID- 26372016 TI - 1DTempPro V2: New Features for Inferring Groundwater/Surface-Water Exchange. AB - A new version of the computer program 1DTempPro extends the original code to include new capabilities for (1) automated parameter estimation, (2) layer heterogeneity, and (3) time-varying specific discharge. The code serves as an interface to the U.S. Geological Survey model VS2DH and supports analysis of vertical one-dimensional temperature profiles under saturated flow conditions to assess groundwater/surface-water exchange and estimate hydraulic conductivity for cases where hydraulic head is known. PMID- 26372017 TI - Enzymatic transglycosylation of ginsenoside Rg1 by rice seed alpha-glucosidase. AB - Six alpha-monoglucosyl derivatives of ginsenoside Rg1 (G-Rg1) were synthesized by transglycosylation reaction of rice seed alpha-glucosidase in the reaction mixture containing maltose as a glucosyl donor and G-Rg1 as an acceptor. Their chemical structures were identified by spectroscopic analysis, and the effects of reaction time, pH, and glycosyl donors on transglycosylation reaction were investigated. The results showed that rice seed alpha-glucosidase transfers alpha glucosyl group from maltose to G-Rg1 by forming either alpha-1,3 (alpha nigerosyl)-, alpha-1,4 (alpha-maltosyl)-, or alpha-1,6 (alpha-isomaltosyl) glucosidic linkages in beta-glucose moieties linked at the C6- and C20-position of protopanaxatriol (PPT)-type aglycone. The optimum pH range for the transglycosylation reaction was between 5.0 and 6.0. Rice seed alpha-glucosidase acted on maltose, soluble starch, and PNP alpha-D-glucopyranoside as glycosyl donors, but not on glucose, sucrose, or trehalose. These alpha-monoglucosyl derivatives of G-Rg1 were easily hydrolyzed to G-Rg1 by rat small intestinal and liver alpha-glucosidase in vitro. PMID- 26372018 TI - Maternal-fetal attachment in blind women using physical model from three dimensional ultrasound and magnetic resonance scan data: six serious cases. AB - OBJECTIVE: The objective of this study is to assess the maternal-fetal attachment (MFA) in six blind pregnant women by means three-dimensional (3D) physical models from 3D ultrasound and magnetic resonance imaging (MRI) scan data. METHODS: We performed a prospective observational cross-sectional study with six blind pregnant women who performed 3D ultrasound and MRI exams to build 3D physical models for their fetuses. The MFA was assessed quantitatively by means a questionnaire of three questions, each one with a score ranging from 0 to 3. We considered MFA values >= 7 to each pregnant woman. The descriptive data were expressed by mean +/- standard deviation (SD). RESULTS: The mean (+/-SD) maternal age was 32 +/- 2.7 years. The mean gestational age at 3DUS and MRI exams were 23.1 +/- 3.7 and 21.3 +/- 0.9 weeks, respectively. The mean of gestational age at delivery was 36.5 +/- 4.7 weeks and all of them were cesarean sections. The mean newborn weight was 2615.8 +/- 871.9 g and the gender was 50% both female and male. The MFA was quantitatively observed in all pregnant women, with maximum value (9) in all of them. CONCLUSION: The MFA was quantitatively observed in all blind pregnant women using 3D physical models. PMID- 26372019 TI - Ocular fundus photography: An alternative to direct ophthalmoscopy for teaching? PMID- 26372020 TI - Exercise and Depressive Symptoms in Older Adults: A Systematic Meta-Analytic Review. AB - Depressive symptoms are common in older adults, but antidepressant medications may be contraindicated or poorly tolerated in this population. Intervention studies demonstrate that exercise may be an effective alternative. This meta analysis included 41 randomized controlled trials of aerobic and nonaerobic exercise interventions investigating the effect of exercise on depressive symptoms in adults aged 60 or older. A random effects model demonstrated that exercise was associated with significantly lower depression severity (SMD = 0.57, 95% CI 0.36-0.78). This effect was not significantly different for different ages of participants, types of control groups, or types of exercise interventions. Studies requiring a diagnosis of depression had significantly greater mean effect sizes than studies that did not require a depression diagnosis (Qbet = 6.843, df = 1, p = .009). These findings suggest that exercise is an effective treatment option for older individuals with depressive symptoms. PMID- 26372021 TI - Italian Percutaneous EVAR (IPER) Registry: outcomes of 2381 percutaneous femoral access sites' closure for aortic stent-graft. AB - AIM: The aim of this paper was to report outcomes of endovascular aneurysm repair with percutaneous femoral access (pEVAR) using Prostar XL and Proglide closure systems (Abbot Vascular, Santa Clara, CA, USA), from the multicenter Italian Percutaneous EVAR (IPER) registry. METHODS: Consecutive patients affected by aortic pathology treated by EVAR with percutaneous access (pEVAR) between January 2010 and December 2014 at seven Italian centers were enrolled in this multicenter registry. All the operators had an experience of at least 50 percutaneous femoral access procedures. Data were prospectively collected into a dedicated online database including patient's demographics, anatomical features, intra- and postoperative outcomes. A retrospective analysis was carried out to report intraoperative and 30-day technical success and access-related complication rate. Uni- and multivariate analyses were performed to identify factors potentially associated with an increased risk of percutaneous pEVAR failure. RESULTS: A total of 2381 accesses were collected in 1322 patients, 1249 (94.4%) male with a mean age of 73.5+/-8.3 years (range 45-97). The overall technical success rate was 96.8% (2305/2381). Major intraoperative access-related complications requiring conversion to surgical cut-down were observed in 3.2% of the cases (76/2381). One month pEVAR failure-rate was 0.25% (6/2381). Presence of femoral artery calcifications resulted to be a significant predictor of technical failure (OR: 1.69; 95% CI: 1.03-2.77; P=0.036) at multivariate analysis. No significant association was observed with sex (P=0.28), obesity (P=0.64), CFA diameter (P=0.32), level of CFA bifurcation (P=0.94) and sheath size >18 F (P=0.24). The use of Proglide was associated with a lower failure rate compared to Prostar XL (2.5% vs. 3.3%) despite not statistically significant (P=0.33). CONCLUSION: The results of the IPER registry confirm the high technical success rate of percutaneous EVAR when performed by experienced operators, even in presence of demanding anatomies. Femoral calcification represents the only predictor of percutaneous access failure. PMID- 26372024 TI - Fiberoptic examination of swallowing in the breastfeeding infant. AB - OBJECTIVES/HYPOTHESIS: Fiberoptic endoscopic evaluation of swallowing (FEES) is the only instrumental exam that can be used to assess swallowing in a breastfeeding infant. There is minimal data on its efficacy and safety in this patient population. Analyze the common indications for, findings of, and safety of FEES exam in breastfeeding infants. STUDY DESIGN: Case series. METHODS: Consecutive 10 months old or younger breastfed infants undergoing a FEES exam between June 1, 2012, and August 1, 2014, at a university-based, tertiary care urban children's hospital were studied. Common indications for and findings of FEES, as well as complications of the procedure, were determined. RESULTS: Twenty four FEES were reviewed on 23 patients. There were 14 males (58%). The average age was 14 weeks, and two children were premature. Common indications for FEES were feeding difficulties (52%), noisy breathing with/without feeding (28%), and cyanosis (16%). Of the patients who participated in active breastfeeding during the exam, a functional swallow was identified in 12.5%. The remaining patients demonstrated dysphagia characterized by laryngeal penetration (83%) and/or direct aspiration (50%). The most common findings were laryngeal edema (29%), anterior displacement of glottis structures (14%), and cobblestoning (11%). There was no morbidity directly associated with the procedure. No cyanosis or respiratory distress occurred during or immediately after the procedure. CONCLUSION: Performing FEES exams on breastfeeding infants is safe and effective. There is no other instrumental evaluation of swallowing to assess dysphagia in this population. LEVEL OF EVIDENCE: 4. Laryngoscope, 126:1681-1686, 2016. PMID- 26372025 TI - Introduction to a Colloquium: Challenges and Opportunities in Advancing Health Literacy Research. PMID- 26372026 TI - The Many Health Literacies: Advancing Research or Fragmentation? AB - Health literacy is the degree to which individuals can obtain, process, understand, and communicate about health-related information needed to make informed health decisions and is an important factor in patient health outcomes and resulting health care costs. Because of its importance across many areas of health, specific attention has been given to studying and measuring health literacy in recent years; however, the field lacks consensus on how health literacy should be defined and measured. As a result, numerous definitions and measures of health literacy exist. This fragmentation and inconsistency creates a barrier to conceptualizing, measuring, and understanding health literacy across health domains and fields. A directed literature search reveals a substantial body of work on health literacy; however, findings from studies often emphasize health literacy within specific health domains, populations, contexts, and languages, which makes the comparison of findings across studies difficult. While there is recognition that the measurement of health literacy should be improved, it is important to take into consideration what can be gained from a general health literacy focus and how this could be applied across domains. PMID- 26372027 TI - Why We Need the Concept of "Mental Health Literacy". AB - In this issue, Mackert and colleagues argue for the benefits of a general health literacy focus, which can be applied across health domains. Using the concept of mental health literacy as an example, this article argues that there are also major advantages of a domain-specific approach. The concept of mental health literacy has had policy impacts and led to the development of interventions, which might not have otherwise occurred. It has also led to the development of assessments specifically targeted at intervention goals. It is concluded that while a general concept of health literacy might be appropriate for some purposes, it does not meet the specific needs of the mental health area. PMID- 26372028 TI - Advocating for a Population-Specific Health Literacy for People With Visual Impairments. AB - Health literacy, the ability to access, process, and understand health information, is enhanced by the visual senses among people who are typically sighted. Emotions, meaning, speed of knowledge transfer, level of attention, and degree of relevance are all manipulated by the visual design of health information when people can see. When consumers of health information are blind or visually impaired, they access, process, and understand their health information in a multitude of methods using a variety of accommodations depending upon their severity and type of impairment. They are taught, or they learn how, to accommodate their differences by using alternative sensory experiences and interpretations. In this article, we argue that due to the unique and powerful aspects of visual learning and due to the differences in knowledge creation when people are not visually oriented, health literacy must be considered a unique construct for people with visual impairment, which requires a distinctive theoretical basis for determining the impact of their mind-constructed representations of health. PMID- 26372029 TI - Health Literacy Research: Isn't There Something Better We Could Be Doing? AB - The number of health literacy articles published each year in scientific journals has increased considerably in recent years. However, the content of those articles continues to focus on the same issues: developing instruments to assess health literacy skills, measuring the health literacy skills of patients, and measuring the reading level of patient education materials. We need to change the focus of health literacy research by studying which approaches to dealing with health literacy result in the best outcomes for patients--making them healthier, having fewer complications, and reducing their health care costs. There is a paucity of high-quality research on such issues, but that is the direction in which the field needs to go. PMID- 26372022 TI - siRNA Versus miRNA as Therapeutics for Gene Silencing. AB - Discovered a little over two decades ago, small interfering RNAs (siRNAs) and microRNAs (miRNAs) are noncoding RNAs with important roles in gene regulation. They have recently been investigated as novel classes of therapeutic agents for the treatment of a wide range of disorders including cancers and infections. Clinical trials of siRNA- and miRNA-based drugs have already been initiated. siRNAs and miRNAs share many similarities, both are short duplex RNA molecules that exert gene silencing effects at the post-transcriptional level by targeting messenger RNA (mRNA), yet their mechanisms of action and clinical applications are distinct. The major difference between siRNAs and miRNAs is that the former are highly specific with only one mRNA target, whereas the latter have multiple targets. The therapeutic approaches of siRNAs and miRNAs are therefore very different. Hence, this review provides a comparison between therapeutic siRNAs and miRNAs in terms of their mechanisms of action, physicochemical properties, delivery, and clinical applications. Moreover, the challenges in developing both classes of RNA as therapeutics are also discussed. PMID- 26372030 TI - Health Literacy Research and Practice: A Needed Paradigm Shift. AB - As a field of research, a viable approach to improving health outcomes, and an important area of policy, health literacy has experienced significant growth and considerable evolution since its broad introduction in the 1990s. Despite that history, far too many practitioners, researchers, and policymakers focusing on clinical medicine, health systems, public health, and health policy remain unaware of and unaffected by the best practices of health literacy. While the inherent promise of health literacy is improved health and well-being, the bulk of research has focused on identifying the negative effects of a lack of health literacy. This strategy is a hindrance to further identifying the utility and increasing the uptake of lessons learned about health literacy in government, business, health care systems, and society. The field needs to reverse direction away from that deficit model of health literacy and focus collective efforts on a positive model of how health literacy can and should be prioritized and utilized to improve health at lower costs. This shift from framing health literacy as a problem to proving the viability and strength of health literacy as a solution will present to policymakers a clear choice to either adopt and promote the best practices of health literacy or suffer the consequences of being the leader who ignored a proven, viable solution to the currently unsustainable health care expenditures and ever-increasing burden of preventable disease, disability, and early death. PMID- 26372031 TI - Should We Be Afraid of Simple Messages? The Effects of Text Difficulty and Illustrations in People With Low or High Health Literacy. AB - It is often recommended that health information should be simplified for people with low health literacy. However, little is known about whether messages adapted to low health literacy audiences are also effective for people with high health literacy, or whether simple messages are counterproductive in this group. Using a two (illustrated vs. text-only) by two (nondifficult vs. difficult text) between subjects design, we test whether older adults with low (n = 279) versus high health literacy (n = 280) respond differently to colorectal cancer screening messages. Results showed that both health literacy groups recalled information best when the text was nondifficult. Reduced text difficulty did not lead to negative attitudes or less intention to have screening among people with high health literacy. Benefits of illustrations, in terms of improved recall and attitudes, were only found in people with low health literacy who were exposed to difficult texts. This was not found for people with high health literacy. In terms of informed decisions, nondifficult and illustrated messages resulted in the best informed decisions in the low health literacy group, whereas the high health literacy group benefited from nondifficult text in general, regardless of illustrations. Our findings imply that materials adapted to lower health literacy groups can also be used for a more general audience, as they do not deter people with high health literacy. PMID- 26372033 TI - Latency as a region contrast: Measuring ERP latency differences with Dynamic Time Warping. AB - Methods for measuring onset latency contrasts are evaluated against a new method utilizing the dynamic time warping (DTW) algorithm. This new method allows latency to be measured across a region instead of single point. We use computer simulations to compare the methods' power and Type I error rates under different scenarios. We perform per-participant analysis for different signal-to-noise ratios and two sizes of window (broad vs. narrow). In addition, the methods are tested in combination with single-participant and jackknife average waveforms for different effect sizes, at the group level. DTW performs better than the other methods, being less sensitive to noise as well as to placement and width of the window selected. PMID- 26372034 TI - Can we predict age at natural menopause using ovarian reserve tests or mother's age at menopause? A systematic literature review. AB - OBJECTIVE: This review aimed to appraise data on prediction of age at natural menopause (ANM) based on antimullerian hormone (AMH), antral follicle count (AFC), and mother's ANM to evaluate clinical usefulness and to identify directions for further research. METHODS: We conducted three systematic reviews of the literature to identify studies of menopause prediction based on AMH, AFC, or mother's ANM, corrected for baseline age. RESULTS: Six studies selected in the search for AMH all consistently demonstrated AMH as being capable of predicting ANM (hazard ratio, 5.6-9.2). The sole study reporting on mother's ANM indicated that AMH was capable of predicting ANM (hazard ratio, 9.1-9.3). Two studies provided analyses of AFC and yielded conflicting results, making this marker less strong. CONCLUSIONS: AMH is currently the most promising marker for ANM prediction. The predictive capacity of mother's ANM demonstrated in a single study makes this marker a promising contributor to AMH for menopause prediction. Models, however, do not predict the extremes of menopause age very well and have wide prediction interval. These markers clearly need improvement before they can be used for individual prediction of menopause in the clinical setting. Moreover, potential limitations for such use include variations in AMH assays used and a lack of correction for factors or diseases affecting AMH levels or ANM. Future studies should include women of a broad age range (irrespective of cycle regularity) and should base predictions on repeated AMH measurements. Furthermore, currently unknown candidate predictors need to be identified. PMID- 26372035 TI - Long-term complications of urinary diversion. AB - PURPOSE OF REVIEW: Radical cystectomy and urinary diversion remains the cornerstone in surgical management of patients with muscle-invasive or high-risk nonmuscle-invasive bladder cancer. This approach has been associated with remarkable increase in patient survival and more patients are now living for years after surgery who may present with long-term complications. This review describes long-term complications associated with urinary diversion including renal function deterioration, voiding dysfunction, stoma and bowel-related complications, ureteroenteric stricture, metabolic disorders, and infectious complications. RECENT FINDINGS: The overall complication rate reported in recent large studies assessing long-term complications of urinary diversion is as high as 60%. Stoma-related complications followed by urinary tract infections are among the most common complications. Some of these complications may occur years after surgery; therefore, long-term follow-up of patients with urinary diversion is of utmost importance. SUMMARY: Long-term regular follow-up is imperative in patients with urinary diversion as nonfatal complications may occur years after surgery. PMID- 26372036 TI - A review of economic evaluations of diagnostic strategies using imaging in men at risk of prostate cancer. AB - PURPOSE OF REVIEW: The role of imaging, particularly MRI, in diagnosing clinically significant prostate cancer is the focus of a rapidly developing body of clinical research. We identified five economic evaluations of multiparametric magnetic resonance imaging (mpMRI) for diagnosing prostate cancer which report very different results. This review aims to explain why the reported cost effectiveness of mpMRI varies so widely. FINDINGS: The studies evaluate the cost effectiveness of mpMRI within different clinical pathways; before biopsy and after a negative biopsy. Although there were important differences in the questions posed, the studies also employed different assumptions about the impact of prostate cancer and its treatment on survival and quality of life. SUMMARY: This review highlights the need for a better standard of reporting around key modelling assumptions. Also, a wider range of sensitivity analyses should explore the impact of these structural assumptions on the model results, in addition to the more commonly acknowledged uncertainty around data inputs for the model parameters. PMID- 26372037 TI - The role of MRI in active surveillance for men with localized prostate cancer. AB - PURPOSE OF REVIEW: Active surveillance is the preferred management strategy for men with low-risk prostate cancer. Challenges in this field include improving patient selection, optimizing follow-up strategies, and identifying appropriate triggers for intervention. Advances in multiparametric MRI (mpMRI) have lead to improved detection of prostate tumors, and MRI has emerged as a tool to monitor men on active surveillance. We aim to review the latest developments in mpMRI to monitor active surveillance patients and describe areas of future research. RECENT FINDINGS: mpMRI targeted prostate biopsy results in a higher detection rate of significant prostate cancer, and a lower probability of detecting insignificant tumors, compared to systematic biopsy. mpMRI-targeted biopsies have improved diagnosis of significant anterior tumors. A small proportion of high grade tumors is missed by mpMRI and targeted biopsy. However, the majority of these tumors are small-volume, Gleason grade 3 + 4 cancers, and their clinical significance is unknown. SUMMARY: mpMRI and targeted prostate biopsy have emerged as tools to improve the accuracy of systematic biopsy to select patients for active surveillance. The role of mpMRI to monitor and trigger intervention in these patients is understudied, and integration of MRI data with clinical characteristics can help many men avoid routine confirmatory biopsy. PMID- 26372038 TI - Immunotherapies for bladder cancer: a new hope. AB - PURPOSE OF REVIEW: We review recent data on immunotherapies for bladder cancer and discuss strategies to maximize the antitumor effect of immunotherapy in solid tumors. RECENT FINDINGS: Anti-programmed death ligand 1 has shown promise in advanced bladder cancer. Clinical trials of immune checkpoint inhibitors as monotherapy or in combination are underway. Here we review strategies for enhancing antitumor immunity using immunomodulating agents or combination treatments that may increase tumor response. SUMMARY: Combining immune checkpoint inhibitors with other treatment modalities may lead to the development of new treatment strategies in advanced bladder cancer; however, identifying predictive biomarkers is essential for appropriate patient selection. PMID- 26372039 TI - The role of multi-parametric MRI in loco-regional staging of men diagnosed with early prostate cancer. AB - PURPOSE OF REVIEW: To review the use of multi-parametric MRI (mpMRI) in loco regional assessment of men with early prostate cancer. RECENT FINDINGS: mpMRI comprises anatomic T2 and T1 sequences supplemented by functional imaging techniques such as diffusion-weighted and dynamic contrast enhanced (DCE) imaging. mpMRI is gaining increasing acceptance for prostate cancer detection and staging of early disease. It can facilitate targeted therapies, guide surgical options and enable active surveillance within suitable patients. The technique can be performed at 1.5 or 3 Tesla, but sequence optimization is critical to successful implementation of mpMRI. T2 and diffusion-weighted sequences are minimal requirements and are often complemented by DCE images. When performed at high spatial resolution, DCE facilitates detection of disease, as well as assessment of extra-capsular extension, distal urethral sphincter and seminal vesicles involvement. Pre-biopsy mpMRI is recommended for both detection and staging as it avoids biopsy artefact, and when normal, has a negative predictive value of 95% for significant cancer. SUMMARY: mpMRI reliably detects clinically significant prostate tumour and ideally should be performed prior to biopsy. It provides an accurate method for local disease staging and facilitates a growing range of treatment options for patients with early disease. PMID- 26372040 TI - A Qualitative Study: NICU Nurses as NICU Parents. AB - BACKGROUND: The neonatal intensive care unit (NICU) nurse who has become a NICU mother is in a unique position to evaluate the NICU experience. Because of her professional experience, she has an understanding of the NICU and healthcare environment. PURPOSE: This study examines the lived experiences of these women, how they coped with their roles as professionals and parents, and how their responses differed from those of NICU mothers without professional NICU experience. METHODS: A narrative qualitative design was utilized to examine the lived experiences of study participants. Face-to-face taped interviews were conducted. Responses were transcribed, then analyzed using both computer-assisted data analysis and manual analysis. RESULTS: Six nurses participated. Their responses were grouped into 6 categories on the basis of previous research. These participants experienced many of the same issues as NICU mothers without professional experience. However, there were meaningful differences. NICU nurses were vocal advocates from the first day of admission. They were also knowledgeable about how to negotiate and work around the system. IMPLICATIONS FOR PRACTICE: NICU nurses who have had the experience of having an infant in the NICU have seen the healthcare system from both sides and can be advocates for family centered care, helping their coworkers understand what works and what does not work for NICU families. IMPLICATIONS FOR RESEARCH: Qualitative research focused on the experiences of healthcare team members who utilize the healthcare system as patients or family members can provide an articulate and educated insight into the experiences of all who use the healthcare system. PMID- 26372041 TI - Is Prenatal Lead Exposure a Concern in Infancy? What Is the Evidence? AB - BACKGROUND: Exposure to unhealthy and unsafe environments cause 1 in 4 deaths in childhood each year. Early exposure to lead beginning prenatally and continuing throughout childhood is one of the mechanisms associated with unhealthy and unsafe environments, particularly in industrial countries and urban communities. Lead is a known heavy metal that crosses the placenta and blood-brain barrier depositing in fetal tissues. PURPOSE: The purpose of this integrative review was to determine which maternal-fetal dyads were at high risk for elevated umbilical cord lead (Pb) levels and to examine the consequences associated with elevated umbilical cord Pb levels. SEARCH STRATEGY: PubMed was searched to obtain English language publications from 2005 to March 2015 for studies examining the effects of prenatal lead exposure on infant outcomes using key terms "lead" combined with "infant." A total of 17 articles were retained for analysis. FINDINGS: Infants with elevated umbilical cord blood lead levels were associated with maternal demographic factors and country of origin. Maternal-specific exposure to lead products prior to or during pregnancy was associated with elevated umbilical cord blood lead levels. The consequences of prenatal lead exposure to the infant at birth anthropometrically were mixed. The evidence on neurological consequences of prenatal exposure to lead appears to reflect changes in cognitive impairment; however, it needs further study. IMPLICATIONS FOR PRACTICE: The major recommendation is primary prevention of lead exposure across the life span. Implementation of policies that reduce the availability of leaded products to reduce leaded products, especially ones aimed at children and women of childbearing age. IMPLICATIONS FOR RESEARCH: Research needs to be focused in 2 directions: (1) prevention of lead exposure during pregnancy and (2) prevention of lead leaching from bones for all women of childbearing age. PMID- 26372042 TI - Quantification of the Iodine Content of Perigastric Adipose Tissue by Dual-Energy CT: A Novel Method for Preoperative Diagnosis of T4-Stage Gastric Cancer. AB - This study investigated the utility of quantifying iodine concentration (IC) in perigastric adipose tissue, using dual-energy computed tomography (DECT), for the detection of T4a-stage gastric cancer. Fifty-four patients with gastric cancer were enrolled at the Fourth Hospital of Hebei Medical University between January and June 2013. Patients were imaged preoperatively with conventional computed tomography (CT) scans and DECT, and the IC in perigastric fat adjacent to the tumor calculated from arterial phase (AP) and portal venous phase (PVP) images. The patients subsequently received surgical treatment (gastrectomy), and histologic analysis of resected specimens was used as a 'gold standard' reference for cancer staging. Receiver operating characteristic (ROC) curve analysis was employed to assess the utility of DECT for identifying T4a-stage gastric cancer, with optimal IC thresholds determined from the area under the ROC curve (AUC). Postoperative histology revealed that 32 patients had serosal invasion (group A), and 22 did not (group B). The accuracy of conventional CT for distinguishing stage T4 from non-T4 stages was 68.5% (37/54). IC was significantly higher in group A than in group B (AP: 0.60+/-0.34 vs. 0.09+/-0.19 mg/mL, p<0.001; PVP: 0.83+/-0.41 vs. 0.27+/-0.21 mg/mL, p<0.001). The sensitivity, specificity and AUC for detecting serosal invasion were 77.1%, 79.2% and 0.89 at an IC threshold of 0.25 mg/mL for AP images; and 80.0%, 79.2% and 0.90 at an IC threshold of 0.45 mg/mL for PVP images. These results indicated that Iodine quantification in perigastric fat using DECT is an accurate method for detecting serosal invasion by gastric cancer. PMID- 26372043 TI - Vertical Transmission of Babesia microti in BALB/c Mice: Preliminary Report. AB - Babesia spp. (Apicomplexa, Piroplasmida) are obligate parasites of many species of mammals, causing a malaria-like infection- babesiosis. Three routes of Babesia infection have been recognized to date. The main route is by a tick bite, the second is via blood transfusion. The third, vertical route of infection is poorly recognized and understood. Our study focused on vertical transmission of B. microti in a well-established mouse model. We assessed the success of this route of infection in BALB/c mice with acute and chronic infections of B. microti. In experimental groups, females were mated on the 1st day of Babesia infection (Group G0); on the 28th day post infection (dpi) in the post- acute phase of the parasite infection (G28); and on the 90th and 150th dpi (G90 and G150 group, respectively), in the chronic phase of the parasite infection. Pups were obtained from 58% of females mated in the post-acute phase (G28) and from 33% of females in groups G90 and G150. Mice mated in the pre-acute phase of infection (G0) did not deliver pups. Congenital B. microti infections were detected by PCR amplification of Babesia 18S rDNA in almost all pups (96%) from the experimental groups G28, G90 and G150. Parasitaemia in the F1 generation was low and varied between 0.01-0.001%. Vertical transmission of B. microti was demonstrated for the first time in BALB/c mice. PMID- 26372044 TI - Reconstruction of Multiple Facial Nerve Branches Using Skeletal Muscle-Derived Multipotent Stem Cell Sheet-Pellet Transplantation. AB - Head and neck cancer is often diagnosed at advanced stages, and surgical resection with wide margins is generally indicated, despite this treatment being associated with poor postoperative quality of life (QOL). We have previously reported on the therapeutic effects of skeletal muscle-derived multipotent stem cells (Sk-MSCs), which exert reconstitution capacity for muscle-nerve-blood vessel units. Recently, we further developed a 3D patch-transplantation system using Sk-MSC sheet-pellets. The aim of this study is the application of the 3D Sk MSC transplantation system to the reconstitution of facial complex nerve-vascular networks after severe damage. Mouse experiments were performed for histological analysis and rats were used for functional examinations. The Sk-MSC sheet-pellets were prepared from GFP-Tg mice and SD rats, and were transplanted into the facial resection model (ST). Culture medium was transplanted as a control (NT). In the mouse experiment, facial-nerve-palsy (FNP) scoring was performed weekly during the recovery period, and immunohistochemistry was used for the evaluation of histological recovery after 8 weeks. In rats, contractility of facial muscles was measured via electrical stimulation of facial nerves root, as the marker of total functional recovery at 8 weeks after transplantation. The ST-group showed significantly higher FNP (about three fold) scores when compared to the NT-group after 2-8 weeks. Similarly, significant functional recovery of whisker movement muscles was confirmed in the ST-group at 8 weeks after transplantation. In addition, engrafted GFP+ cells formed complex branches of nerve-vascular networks, with differentiation into Schwann cells and perineurial/endoneurial cells, as well as vascular endothelial and smooth muscle cells. Thus, Sk-MSC sheet-pellet transplantation is potentially useful for functional reconstitution therapy of large defects in facial nerve-vascular networks. PMID- 26372045 TI - Surgical risk factors for recurrence of inverted papilloma. AB - OBJECTIVES/HYPOTHESIS: To identify variations in surgical technique that impact the recurrence of inverted papilloma following endoscopic excision. STUDY DESIGN: Retrospective cohort. METHODS: Data from 127 consecutive patients who underwent endoscopic excision of inverted papilloma and oncocytic papilloma at a tertiary care medical center from 1998 to 2011 were reviewed. Patient demographics, comorbidities, tumor stage, and intraoperative details, including tumor location and management of the base, were evaluated to identify factors associated with tumor recurrence. RESULTS: Recurrence of papilloma occurred in 16 patients (12.6%). Mean time to recurrence was 31.0 months (range, 5.2-110.0 months). Mucosal stripping alone was associated with a recurrence rate of 52.2% (12/23 patients), compared to 4.9% (3/61 patients) when the tumor base was drilled, 4.7% (1/21 patients) when it was cauterized, and 0.0% (0/22 patients) when it was completely excised (P = .001). Increased recurrence rate was associated with tumors located in the maxillary sinus (P = .03), as well as the performance of endoscopic medial maxillectomy (P = .001) and external frontal approaches (P = .02). CONCLUSIONS: Drilling, cauterizing, or completely excising the bone underlying the tumor base during endoscopic resection reduces the recurrence rate of inverted and oncocytic papilloma, when compared to mucosal stripping alone. Surgeons who perform endoscopic resection of these tumors should consider utilization of these techniques when possible. LEVEL OF EVIDENCE: 4. PMID- 26372046 TI - Behavioral and Psychiatric Phenotypes in 22q11.2 Deletion Syndrome. AB - 22q11.2 Deletion syndrome (22q11.2DS) is a chromosomal microdeletion that affects approximately 40 to 50 genes and affects various organs and systems throughout the body. Detection is typically achieved by fluorescence in situ hybridization after diagnosis of one of the major features of the deletion or via chromosomal microarray or noninvasive prenatal testing. The physical phenotype can include congenital heart defects, palatal and pharyngeal anomalies, hypocalcemia/hypoparathyroidism, skeletal abnormalities, and cranial/brain anomalies, although prevalence rates of all these features are variable. Cognitive function is impaired to some degree in most individuals, with prevalence rates of greater than 90% for motor/speech delays and learning disabilities. Attention, executive function, working memory, visual-spatial abilities, motor skills, and social cognition/social skills are affected. The deletion is also associated with an increased risk for behavioral disorders and psychiatric illness. The early onset of psychiatric symptoms common to 22q11.2DS disrupts the development and quality of life of individuals with the syndrome and is also a potential risk factor for later development of a psychotic disorder. This review discusses prevalence, phenotypic features, and management of psychiatric disorders commonly diagnosed in children and adolescents with 22q11.2DS, including autism spectrum disorders, attention deficit/hyperactivity disorder, anxiety disorders, mood disorders, and schizophrenia/psychotic disorders. Guidelines for the clinical assessment and management of psychiatric disorders in youth with this syndrome are provided, as are treatment guidelines for the use of psychiatric medications. PMID- 26372047 TI - Combating Obesity in Head Start: Outdoor Play and Change in Children's Body Mass Index. AB - OBJECTIVE: To determine whether increased outdoor play time at Head Start was associated with greater changes in body mass index (BMI) over the course of a preschool year. METHOD: The authors used data from 2810 children from the Family and Child Experiences Survey 2006 cohort. With children's spring BMI as the outcome (both continuously measured and dichotomized to measure the risk of obesity), the authors conducted weighted regression analyses, controlling for child-level, family-level, and school-level covariates, including preschool entry BMI. RESULTS: Children played outdoors at school for roughly 37 minutes per day, with little variation across half-day and full-day programs. The more children played outdoors, the more their BMI decreased over the preschool year (beta = .05, 95% confidence interval (CI) [-0.08 to -0.01]) and the less likely they were to be obese (odds ratio = 0.99, 95% CI [0.98-0.99]). The difference between high levels and low levels of outdoor play corresponded to 0.18 BMI points and a 42% reduction in children's risk of obesity. Sixty minutes was the "tipping point" for the association between outdoor play time and improvements in children's BMI. These associations were also stronger among children who were obese at the start of the year, less active at home, and living in unsafe neighborhoods. CONCLUSION: Outdoor play time at Head Start is associated with decreases in children's BMI scores and, thus, may serve as an important means of preventing obesity. Head Start programs should consider establishing clear guidelines encouraging more outdoor time. PMID- 26372050 TI - Medialization thyroplasty under intubation anesthesia to restore the voice after cordectomy. PMID- 26372049 TI - ICSH recommendations for assessing automated high-performance liquid chromatography and capillary electrophoresis equipment for the quantitation of HbA2. AB - Automated high performance liquid chromatography and Capillary electrophoresis are used to quantitate the proportion of Hemoglobin A2 (HbA2 ) in blood samples order to enable screening and diagnosis of carriers of beta-thalassemia. Since there is only a very small difference in HbA2 levels between people who are carriers and people who are not carriers such analyses need to be both precise and accurate. This paper examines the different parameters of such equipment and discusses how they should be assessed. PMID- 26372051 TI - Color Stability of CAD/CAM Fabricated Inlays after Accelerated Artificial Aging. AB - PURPOSE: To investigate the influence of accelerated artificial aging on the color stability of three different inlay restorations produced with a CAD/CAM system. MATERIALS AND METHODS: Thirty non-carious human mandibular molar teeth were used. The teeth were embedded in autopolymerizing acrylic resin blocks. Standard Class I inlay cavities were prepared, and the teeth were randomly divided into three groups (n = 10) to fabricate inlay restorations: (1) a feldspathic-ceramic group, (2) a resin nano-ceramic group, and (3) a leucite glass-ceramic group. Optical impressions were made with CEREC software, and the restorations were designed and then milled. The inlays were adhesively cemented with a dual-polymerizing resin cement and left in distilled water at room temperature for 1 week. Color measurements were performed with a spectrophotometer before and after accelerated aging in a weathering machine with a total energy of 150 kJ/m(2) . Changes in color (?E, ?L, ?a, ?b, ?C) were determined using the CIE L*a*b* system. The results were assessed using a one-way ANOVA and Tukey's HSD test (p = 0.05). RESULTS: The color changes of the materials ranged from 2.1 to 9.29. The highest color change was seen in the resin nano-ceramic material. This change was not clinically acceptable (?E > 5.5). No significant differences were found in the ?L and ?a values of the test groups. CONCLUSIONS: Color changes were observed in each evaluated material after accelerated aging. All CAD/CAM inlays became darker in appearance, more saturated, a little reddish, and more yellow. PMID- 26372048 TI - Shaping Neuronal Network Activity by Presynaptic Mechanisms. AB - Neuronal microcircuits generate oscillatory activity, which has been linked to basic functions such as sleep, learning and sensorimotor gating. Although synaptic release processes are well known for their ability to shape the interaction between neurons in microcircuits, most computational models do not simulate the synaptic transmission process directly and hence cannot explain how changes in synaptic parameters alter neuronal network activity. In this paper, we present a novel neuronal network model that incorporates presynaptic release mechanisms, such as vesicle pool dynamics and calcium-dependent release probability, to model the spontaneous activity of neuronal networks. The model, which is based on modified leaky integrate-and-fire neurons, generates spontaneous network activity patterns, which are similar to experimental data and robust under changes in the model's primary gain parameters such as excitatory postsynaptic potential and connectivity ratio. Furthermore, it reliably recreates experimental findings and provides mechanistic explanations for data obtained from microelectrode array recordings, such as network burst termination and the effects of pharmacological and genetic manipulations. The model demonstrates how elevated asynchronous release, but not spontaneous release, synchronizes neuronal network activity and reveals that asynchronous release enhances utilization of the recycling vesicle pool to induce the network effect. The model further predicts a positive correlation between vesicle priming at the single-neuron level and burst frequency at the network level; this prediction is supported by experimental findings. Thus, the model is utilized to reveal how synaptic release processes at the neuronal level govern activity patterns and synchronization at the network level. PMID- 26372053 TI - In Situ Assembly of Hydrophilic and Hydrophobic Nanoparticles at Oil-Water Interfaces as a Versatile Strategy To Form Stable Emulsions. AB - We report a conceptually new strategy for forming particle-stabilized emulsions. We begin with stable, dilute suspensions of highly hydrophilic nanoparticles in water and hydrophobic nanoparticles in oil. When the two suspensions are mixed, attractive interactions between the hydrophilic and hydrophobic particles cause them to assemble at the oil-water interfaces into partially wettable or Janus like clusters that effectively stabilize emulsions. By tuning the ratio of hydrophilic to hydrophobic particles in the clusters, both water-in-oil as well as oil-in-water emulsions can be formed. The van der Waals interaction energy between two particle types across an aqueous-organic interface provide a systematic guide to particle and liquid combinations that can form stable emulsions using our strategy, or identify when emulsions will not form. Our experiments and analysis provide a new platform for the formation of particle stabilized emulsions and can be used to combine particles of different functionalities at emulsion droplet surfaces for generating novel materials. PMID- 26372054 TI - Negative affect does not impact semantic retrieval failure monitoring. AB - This study investigated the effect of the emotional nature of to-be-retrieved material on semantic retrieval monitoring. Across 2 groups, participants were either asked whether they have experienced a tip-of-the-tongue (TOT) state or to make a feeling-of-knowing (FOK) judgment. We examined the overall reporting rate as well as subjective (not accompanied by partial information recall) TOT and FOK reporting, comparing whether these differed between emotional (negatively valenced and arousing) and neutral items. The results demonstrated that emotion does not impact semantic TOT and FOK reports, a conclusion supported by Bayesian analysis of the results. The outcomes extend other findings in the metamemory literature, and are discussed with a focus on future research avenues concerning interactions between emotion and metamemory. PMID- 26372055 TI - Learning to selectively attend from context-specific attentional histories: A demonstration and some constraints. AB - Multiple lines of evidence from the attention and performance literature show that attention filtering can be controlled by higher level voluntary processes and lower-level cue-driven processes (for recent reviews see Bugg, 2012; Bugg & Crump, 2012; Egner, 2008). The experiments were designed to test a general hypothesis that cue-driven control learns from context-specific histories of prior acts of selective attention. Several web-based flanker studies were conducted via Amazon Mechanical Turk. Attention filtering demands were induced by a secondary one-back memory task after each trial prompting recall of the last target or distractor letter. Blocking recall demands produced larger flanker effects for the distractor than target recall conditions. Mixing recall demands and associating them with particular stimulus-cues (location, colour, letter, and font) sometimes showed rapid, contextual control of flanker interference, and sometimes did not. The results show that subtle methodological parameters can influence whether or not contextual control is observed. More generally, the results show that contextual control phenomena can be influenced by other sources of control, including other cue-driven sources competing for control. PMID- 26372056 TI - Language, visual working memory, and dot subtraction: What counts? AB - To investigate cognitive factors affecting subtraction of visual objects, we adapted the dot subtraction task developed by Pica, Lemer, Izard, and Dehaene (2004), who used it to investigate calculation by the Munduruku, an indigene group in Brazil that has a limited number word vocabulary. In the dot subtraction task, briefly displayed arrays of moving dots are used to represent the quantities for subtraction. We tested 40 Canadian university students' dot enumeration, Arabic digit subtraction, visual working memory, and performance on the dot subtraction task with dot display durations of 2, 1.5, 1, and .5 s. In the 2 s condition, error rates were uniformly low, whereas in the .5 s condition, error rates increased sharply as the minuend increased from 4 to 8, as was observed with the Munduruku. Individual differences in dot subtraction accuracy were predicted by dot enumeration skill with longer dot display durations but were predicted by visual working memory efficiency with shorter durations. Pica et al. (2004) attributed the Munduruku participants' very poor subtraction to the absence of counting words, but our results show that a shift to reliance on visual working memory is a nonlinguistic factor that comes into play in the dot subtraction task when time to encode the dot arrays is limited. PMID- 26372057 TI - Bilingual lexical selection as a dynamic process: Evidence from Arabic-French bilinguals. AB - The nature of the lexical selection process in bilingual spoken word production is one of the pending questions of research on bilingualism. According to one view this competitive process is language-specific, while another holds that it is language-nonspecific (i.e., lexical competition is cross-linguistic). In recent years, research on bilingual language production has seen the rise of a third view that postulates that lexical selection is in fact dynamic and may function as language-specific or nonspecific depending on a number of factors. The aim of the present study was to investigate the lexical selection process among moderately proficient bilinguals whose two languages are typologically distant: Tunisian Arabic and French. The picture-word interference task was used in two experiments where moderately proficient Tunisian Arabic (L1)-French (L2) bilinguals were asked to name pictures in their L2 while ignoring auditory distractors (semantic, phono-translation, phonological, or unrelated) in their L2 (Experiment 1) or their L1 (Experiment 2). Thus, the language context was entirely monolingual in Experiment 1 and bilingual in Experiment 2. In Experiment 1, only a phonological facilitation effect was observed. In Experiment 2, interference was found in the phono-translation, semantic, and phonological conditions. Taken together, these results indicate that cross-language competition occurs among moderately proficient Tunisian Arabic-French bilinguals only in a bilingual context (Experiment 2) as indexed by the phono-translation interference effect observed. Our findings are in line with the recent hypothesis that lexical selection is a dynamic process modulated by factors like language similarity, language proficiency, and the experimental language context. PMID- 26372058 TI - Age-related differences in arithmetic strategy sequential effects. AB - In this article, I review a series of new findings concerning how age-related changes in strategic variations are modulated by sequential effects. Sequential effects refer to how strategy selection and strategy execution on current problems are influenced by which strategy is used on immediately preceding problems. Two sequential effects during strategy selection (i.e., strategy revisions and strategy perseverations) and during strategy execution (i.e., strategy switch costs and modulations of poorer strategy effects) are presented. I also discuss how these effects change with age during adulthood. These phenomena are important, as they shed light on arithmetic processes and how these processes change with age during adulthood. In particular, they speak to the role of executive control while participants select and execute arithmetic strategies. Finally, I discuss the implications of sequential effects for theories of strategies and of arithmetic. PMID- 26372059 TI - Evo-Devo gene toolkit update: at least seven Pax transcription factor subfamilies in the last common ancestor of bilaterian animals. PMID- 26372060 TI - New insights into the vertebral Hox code of archosaurs. AB - Variation in axial formulae (i.e., number and identity of vertebrae) is an important feature in the evolution of vertebrates. Vertebrae at different axial positions exhibit a region-specific morphology. Key determinants for the establishment of particular vertebral shapes are the highly conserved Hox genes. Here, we analyzed Hox gene expression in the presacral vertebral column in the Nile crocodile in order to complement and extend a previous examination in the alligator and thus establish a Hox code for the axial skeleton of crocodilians in general. The newly determined expression of HoxA-4, C-5, B-7, and B-8 all revealed a crocodilian-specific pattern. HoxA-4 and HoxC-5 characterize cervical morphologies and the latter furthermore is associated with the position of the forelimb relative to the axial skeleton. HoxB-7 and HoxB-8 map exclusively to the dorsal vertebral region. The resulting expression patterns of these two Hox genes is the first description of their exact expression in the archosaurian embryo. Our comparative analyses of the Hox code in several amniote taxa provide new evidence that evolutionary differences in the axial skeleton correspond to changes in Hox gene expression domains. We detect two general processes: (i) expansion of a Hox gene's expression domain as well as (ii) a shift of gene expression. We infer that the ancestral archosaur Hox code may have resembled that of the crocodile. In association with the evolution of morphological traits, it may have been modified to patterns that can be observed in birds. PMID- 26372061 TI - Hemipenes in females of the Mexican viviparous lizard Barisia imbricata (Squamata: Anguidae): an example of heterochrony in sexual development. AB - The sexual development of saurians follows a similar pattern to that described for other amniotes. Changes in the timing or sequence of development events are known as heterochrony. We describe the pattern of sexual development in the viviparous Mexican lizard Barisia imbricata and report heterochrony in the regression of hemipenes in this lizard. We collected gestating females; some lizards were subjected to partial hysterectomy and the embryos were processed using routine histological technique to assess gonadal development; the remaining embryos were used to assess the development of hemipenes. Other pregnant females were kept in captivity in individual terraria until the time of delivery. All neonates were sexed by eversion of hemipenes and some of their body characteristics were recorded. Several neonates were sacrificed and processed to establish gonadal histology and the young of the remaining litters were maintained in captivity to observe the fate of the hemipenes in both sexes. Gonadal development began at embryonic stage 33 and the hemipenes were visible at the same stage. In the neonates, the ovary contained oogonias and ovarian follicles, whereas the testicles showed testicular cords. All neonates had hemipenes and sex could only be established through direct observation of the reproductive ducts and gonadal histology. The hemipenes regression in the females begins after approximately 7 months of postnatal development and concludes at about 15 months of age. We think that the delayed regression of the hemipenes reflects evolutionary differences among reptiles and may be an indication of a stage in the evolutionary process of this species. PMID- 26372062 TI - Post-embryonic development of the Early Ordovician (ca. 480 Ma) trilobite Apatokephalus latilimbatus Peng, 1990 and the evolution of metamorphosis. AB - In many marine invertebrates metamorphosis entails a shift from a free-swimming larva to a benthic juvenile or adult. However, how the metamorphosis-entailing "indirect development" in arthropods arose from direct-developing ancestor is poorly understood. Trilobites left a rich fossil record, and some trilobite lineages had a metamorphosis-undergoing early developmental stage, termed the "asaphoid protaspis"-stage, providing a good opportunity to elucidate the rise of indirect development. Among others, the Ordovician representatives of Remopleuridioidea are known to possess a highly bulbous "asaphoid protaspis," while the Furongian (Late Cambrian) remopleuridioidean genus Haniwa did not possess it. Here we show the post-embryonic development of the remopleuridioidean trilobite, Apatokephalus latilimbatus, from the Tremadocian (485.4 Ma-477.7 Ma) Dongjeom Formation, Korea. The post-embryonic development of A. latilimbatus contains a free-swimming "commutavi protaspis" (a term replacing "asaphoid protaspis"). Interestingly, the earlier protaspid stage shows more similar morphology and size to the meraspis than the commutavi protaspid stage does. This indicates that the commutavi protaspid stage was intercalated into the ancestral direct development as a specialized stage for a better dispersal, and thus the "commutavi protaspis" of A. latilimbatus represents the initial phase of the evolution of indirect development. The duration of the free-swimming phase became longer in more derived remoplueridioidean trilobites, implying that the intercalated free-swimming strategy became emphasized during subsequent evolution. The morphological gap between the commutavi protaspis and the subsequent earliest meraspis provides a convincing case for the "selective independence" of developmental stages, explaining the various morphologies of commutavi protaspides in many trilobite lineages. PMID- 26372064 TI - Self-healable and reversible liposome leakage by citrate-capped gold nanoparticles: probing the initial adsorption/desorption induced lipid phase transition. AB - We herein report that the adsorption/desorption of citrate-capped gold nanoparticles (AuNPs) transiently causes leakage in fluid phase DOPC liposomes, while the liposomes do not leak with AuNPs capped with mercaptopropionic acid (MPA). Leakage also fails to occur for gel phase DPPC liposomes. Citrate-capped (but not MPA-capped) AuNPs raise the phase transition temperature of DPPC. We conclude that citrate-capped AuNPs interact with the PC liposomes very strongly, inducing a local fluid-to-gel lipid phase transition for DOPC. Leakage takes place during this transition, and the membrane integrity is resumed after the transition. Citrate-capped AuNPs allow stronger van der Waals forces than MPA capped AuNPs with PC liposomes, since the latter are separated from the liposome surface by the ~0.3 nm MPA layer. PMID- 26372063 TI - Patterns of variation and covariation in the shapes of mandibular bones of juvenile salmonids in the genus Oncorhynchus. AB - What is the nature of evolutionary divergence of the jaw skeleton within the genus Oncorhynchus? How can two associated bones evolve new shapes and still maintain functional integration? Here, we introduce and test a "concordance" hypothesis, in which an extraordinary matching of the evolutionary shape changes of the dentary and angular articular serves to preserve their fitting together. To test this hypothesis, we examined morphologies of the dentary and angular articular at parr (juvenile) stage, and at three levels of biological organization-between salmon and trout, between sister species within both salmon and trout, and among three types differing in life histories within one species, Oncorhynchus mykiss. The comparisons show bone shape divergences among the groups at each level; morphological divergence between salmon and trout is marked even at this relatively early life history stage. We observed substantial matching between the two mandibular bones in both pattern and amount of shape variation, and in shape covariation across species. These findings strongly support the concordance hypothesis, and reflect functional and/or developmental constraint on morphological evolution. We present evidence for developmental modularity within both bones. The locations of module boundaries were predicted from the patterns of evolutionary divergences, and for the dentary, at least, would appear to facilitate its functional association with the angular articular. The modularity results suggest that development has biased the course of evolution. PMID- 26372065 TI - Solvent-Controlled Synthesis of NiO-CoO/Carbon Fiber Nanobrushes with Different Densities and Their Excellent Properties for Lithium Ion Storage. AB - NiO-CoO nanoneedles are grown on carbon fibers by a solvothermal strategy to form nanobrushes. The density of nanobrushes can be easily controlled by altering the solvents. The synthesis mechanism of NiO-CoO/carbon fiber nanobrushes is investigated by the time-dependent experiments in detail. As anodes for lithium ion batteries, the NiO-CoO/carbon fiber nanobrushes synthesized in ethanol show excellent properties with a discharge capacity of 801 mA h g(-1) after 200 cycles at a current density of 200 mA g(-1). The improvement can be ascribed to the carbon fibers as the highway for electrons and the interspace between NiO-CoO nanoneedles to accommodate the volume change and maintain the structural stability. PMID- 26372066 TI - The 'Povl'-itics of editing. PMID- 26372067 TI - Role of thioredoxin nitration in bleomycin-induced pulmonary fibrosis in rats. AB - Oxidant stimulation has been suggested to play an important role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Our study aimed to investigate the role and mechanisms of thioredoxin (Trx) nitration during the development of IPF. A rat model of IPF was established by intratracheal instillation of bleomycin (BLM). Male Wistar rats were randomly distributed among the control group and BLM-treated group, in which rats were intratracheally instilled with a single dose of BLM (5.0 mg/kg body mass in 1.0 mL phosphate buffered saline). At 7 or 28 days after instillation the rats were euthanized. Histopathological and biochemical examinations were performed. The activity and protein level of thioredoxin were assessed. The thioredoxin nitration level was determined using immunoprecipitation and immunoblotting techniques. Our results demonstrated that protein tyrosine nitration increased in the BLM-treated group compared with the control group. Trx activity decreased in the BLM group compared with control group, whereas Trx expression and nitration level increased dramatically in the BLM group compared with the control group. Our results indicated that Trx nitration might be involved in the pathogenesis of IPF. PMID- 26372068 TI - Elusive beta-Zn8Sb7: A New Zinc Antimonide Thermoelectric. AB - Zn8Sb7 was theoretically predicted to exhibit superior thermoelectric properties; however a crystalline phase with a similar composition was only stabilized in the form of nanoparticles. We report a new metastable compound, beta-Zn8Sb7, which was synthesized in the form of bulk polycrystalline powder via high-temperature solid-state annealing followed by quenching. Single crystal X-ray diffraction indicates that beta-Zn8Sb7 crystallizes in a new structure type (noncentrosymmetric orthorhombic space group Pmn21 (no. 31) with unit cell parameters of a = 15.029(1) A, b = 7.7310(5) A, c = 12.7431(9) A, which is different from the nanoparticulate phase. According to differential scanning calorimetry, the beta-Zn8Sb7 phase melts incongruently at 825(5) K. beta-Zn8Sb7 is a p-type semiconductor with high Seebeck thermopower and low thermal conductivity stemming from the complex crystal structure. beta-Zn8Sb7 exhibits a promising thermoelectric figure-of-merit, zT, of 0.33 at 400 K, which is comparable to the state-of-the-art thermoelectric materials based on binary zinc antimonides. PMID- 26372069 TI - A multifunctional metal-organic framework based tumor targeting drug delivery system for cancer therapy. AB - Drug delivery systems (DDSs) with biocompatibility and precise drug delivery are eagerly needed to overcome the paradox in chemotherapy that high drug doses are required to compensate for the poor biodistribution of drugs with frequent dose related side effects. In this work, we reported a metal-organic framework (MOF) based tumor targeting DDS developed by a one-pot, and organic solvent-free "green" post-synthetic surface modification procedure, starting from the nanoscale MOF MIL-101. Owing to the multifunctional surface coating, premature drug release from this DDS was prevented. Due to the pH responsive benzoic imine bond and the redox responsive disulfide bond at the modified surface, this DDS exhibited tumor acid environment enhanced cellular uptake and intracellular reducing environment triggered drug release. In vitro and in vivo results showed that DOX loaded into this DDS exhibited effective cancer cell inhibition with much reduced side effects. PMID- 26372070 TI - Protein quantification using controlled DNA melting transitions in bivalent probe assemblies. AB - Homogenous protein assays, despite the potential for mix-and-read workflows, have eluded widespread acceptance due to interferences in biological matrices and limited multiplexability. Here, we employ standard qPCR instrumentation for thermofluorimetric analysis of bivalent probe (TFAB) assemblies, allowing protein levels to be quantitatively translated into multiplexable DNA melting transitions within 30 min. As protein-bound bivalent probes are thermodynamically more stable than unbound probes, differential thermal analysis can remove background analytically, without physical separation. Using either antibody-oligonucleotides or aptamers as probes, TFAB is validated for protein quantification in buffer, human serum, and human plasma and for assaying hormone secretions from endocrine cells. The direct optical method exhibits superior scalability, allowing detection of only 1 amol of protein in microfluidic channels of 100 pL volume. Overall, we demonstrate TFAB as a robust and generalizable homogeneous protein assay with superior performance in biological matrices. PMID- 26372071 TI - Mercury and Selenium Balance in Endangered Saimaa Ringed Seal Depend on Age and Sex. AB - The endangered Saimaa ringed seal (Pusa hispida saimensis) is exposed to relatively high concentrations of mercury (Hg) in freshwaters poor in selenium (Se), a known antagonist of Hg. The impact of age and sex on the bioaccumulation of Hg and Se was studied by analyzing liver, muscle, and hair samples from seals of different age groups. Adult females were found to accumulate significantly more Hg in the liver (with ca. 60% as HgSe), and less Hg in the muscles compared to adult males, which may be explained by accelerated metabolism during gestation and lactation. In adult seals, molar Se:Hg ratios in the muscles fall below one, which is considered a threshold for the emergence of adverse effects. As a result, Saimaa ringed seals may be at risk of developing health and reproductive problems. According to mass balance calculations, the pups are exposed to considerable amounts (MUg/d) of mercury during gestation, although lactation is their main exposure route. In lanugo pups, Hg concentrates in the hair, and molting serves as a main detoxification route. For other age groups, demethylation followed by the formation of HgSe is the main detoxification route, and the demethylation capability develops in pups by the time of weaning. PMID- 26372072 TI - Observation of the Long Afterglow in AlN Helices. AB - The coupling effect between nitrogen-vacancies (VN) and aluminum-interstitial sites (Ali) is investigated theoretically and experimentally in AlN helices. First-principles calculations predict a photoluminescence emission peak at approximately 600 nm in AlN doped with complex-defect (VNAli). A typical long afterglow (persistent luminescence) was observed in unintentionally doped AlN helices by introducing the complex-defect of (VNAli). An analysis of the luminescent characteristics indicated that the mechanism behind this afterglow is the complex-defect level and complex-defect density. These findings may further enrich the thoughts of defects in the wide band gap semiconductor of AlN. PMID- 26372073 TI - Reengineered tricyclic anti-cancer agents. AB - The phenothiazine and dibenzazepine tricyclics are potent neurotropic drugs with a documented but underutilized anti-cancer side effect. Reengineering these agents (TFP, CPZ, CIP) by replacing the basic amine with a neutral polar functional group (e.g., RTC-1, RTC-2) abrogated their CNS effects as demonstrated by in vitro pharmacological assays and in vivo behavioral models. Further optimization generated several phenothiazines and dibenzazepines with improved anti-cancer potency, exemplified by RTC-5. This new lead demonstrated efficacy against a xenograft model of an EGFR driven cancer without the neurotropic effects exhibited by the parent molecules. Its effects were attributed to concomitant negative regulation of PI3K-AKT and RAS-ERK signaling. PMID- 26372074 TI - Soluble epoxide hydrolase inhibitory activity of anthraquinone components from Aloe. AB - Aloe is a short-stemmed succulent herb widely used in traditional medicine to treat various diseases and as raw material in cosmetics and heath foods. In this study, we isolated and identified two new anthraquinone derivatives, aloinoside C (6) and aloinoside D (7), together with six known compounds from an aqueous dissolved Aloe exudate. Their structures were identified by spectroscopic analysis. The inhibitory effects of the isolated compounds on soluble epoxide hydrolase (sEH) were evaluated. Compounds 1-8 inhibited sEH activity potently, with IC50 values ranging from 4.1+/-0.6 to 41.1+/-4.2 MUM. A kinetic analysis of compounds 1-8 revealed that the inhibitory actions of compounds 1, 6 and 8 were non-competitive, whereas those of compounds 2-5 and 7 were the mixed-type. Molecular docking increases our understanding of receptor-ligand binding of all compounds. These results demonstrate that compounds 1-8 from Aloe are potential sEH inhibitors. PMID- 26372075 TI - Synthesis and antiviral activity of maleopimaric and quinopimaric acids' derivatives. AB - A series of maleopimaric and quinopimaric acids' derivatives modified in the E ring, at the carbonyl- and carboxyl-groups were synthesized and evaluated for their activity in vitro against respiratory viruses (influenza; rhinovirus; adenovirus; and SARS), papilloma virus, and hepatitis B and C viruses. The antiviral screening of levopimaric acid diene adducts derivatives was carried out with minimal effect on SARS and influenza type B viruses. Excellent antiviral activity of the ozonolysis product of maleopimaric acid and dihydroquinopimaric methyl-(2-methoxycarbonyl)ethylene amide was found toward papilloma virus (HPV-11 strain) with the selectivity index of SI 30 and 20, respectively. Methyl (2 methoxycarbonyl)ethylene-, 1beta-hydroxy-5'-kaprolaktamo- and 4beta-hydroxy 4alpha,14alpha-epoxy-13(15)-ene-dihydroquinopimaric acid derivatives have also shown activity against replication of HCV nucleic acid and low toxicity. PMID- 26372076 TI - Thermoresponsive hydrogel maintains the mouse embryonic stem cell "naive" pluripotency phenotype. AB - A chemically defined thermoresponsive hydrogel, poly(AEtMA-Cl-co-DEAEA) cross linked with N,N'-methylenebisacrylamide, which allows enzyme-free passaging, was used as a substrate to culture murine embryonic stem cells (mESCs) under defined and undefined conditions. Analysis of 14 stem cell markers showed that the mESCs remained in a "naive" state of pluripotency with differentiation potential to form endoderm, mesoderm, and ectoderm derived lineages. These results validate the use of a chemically defined hydrogel for standardised and inexpensive mESC culture. PMID- 26372077 TI - drawMD APP-aided preoperative anesthesia education reduce parents anxiety and improve satisfaction. AB - OBJECTIVE: There is no existing standard format for preoperative anesthesia education. The drawMD APP is an visible preoperative education tool. The aim of this study was to evaluate the effects of drawMD APP on pre-operative anesthesia education. METHODS: The parents were randomized to receive drawMD APP-aided pre operative anesthesia education or standard verbal education. Parental anxiety was measured before education (T0) and immediately after education (T1), and after operation (T4). Children's anxiety was assessed before education (T0) and at the operation room (T2). Children's emergence behavior and Parents' satisfaction were assessed after operation (T4). RESULTS: The parents' anxiety levels at T1 and T4 were significantly lower than that of the control. The satisfaction scores in the drawMD group were significantly higher than that in the control group. There were no differences in children's anxiety and the incidence of emergence delirium between the two groups. CONCLUSIONS: The drawMD APP-aided pre-operative education is effective in the reduction of parental pre-operative anxiety and in improvement of parents' satisfaction, but has no influence on children. PRACTICE IMPLICATIONS: Anesthesiologists can consider using drawMD APP to conduct pre operative education in parents whose children are scheduled for surgery. PMID- 26372078 TI - Detecting intratumoral heterogeneity in routine breast-HER2 testing: low yield of testing multiple blocks. AB - BACKGROUND: Intratumoral heterogeneity can lead to uncertainty in breast carcinoma HER2 testing, both with respect to pathology reporting and clinical significance. The standard practice is to perform breast biomarker testing on a single representative section of tumor; however, concern over heterogeneity often leads to testing on additional tissue blocks. Our objective was to assess the diagnostic yield of testing multiple blocks of a single invasive breast carcinoma. METHODS: We performed a retrospective review of 139 consecutive cases (between 2006 and 2012) in which clinical HER2 testing was performed in multiple blocks. Tumor characteristics and HER2 studies (both immunohistochemistry and data from in situ hybridization) were reviewed. Regional differences in morphology and HER2 immunoreactivity were recorded. In situ hybridization was performed in 25 of 139 of the cases; patterns of genetic heterogeneity were reviewed. We audited discordances in HER2 result between blocks. RESULTS: Testing of multiple blocks yielded no additional HER2 information in 134 (96.4%) of 139 cases. Morphologic differences or heterogeneity in HER2 expression was observed in 22 (15.8%) of 139 of cases. Only 5 of these showed differences in HER2 between blocks, of which 4 were associated with equivocal HER2 immunohistochemistry, and 4 were high-grade. CONCLUSIONS: In the vast majority of cases, even those with heterogeneity, testing of a single block is sufficient for an accurate HER2 determination. High-grade tumors with equivocal HER2 status and observable heterogeneity are more likely to yield a different result on testing of additional blocks. PMID- 26372079 TI - [In time: misuse and overuse of amino acid formulas in cow milk allergy]. PMID- 26372080 TI - Metabolic fate of 3alpha,5-cycloandrostanes in the endogenous lactonization pathway of Aspergillus tamarii KITA. AB - A series of 3alpha,5-cycloandrostane analogues with a range of functionality (6alpha and 6beta alcohols and ketone) at carbon 6 were tested in the endogenous lactonization pathway in Aspergillus tamarii KITA. This metabolic route converts progesterone to testololactone in high yield through a four step enzymatic pathway. To date, no studies have looked at the effect of steroids devoid of polar functionality at carbon 3 and their subsequent metabolic fate by fungi which contain Baeyer-Villiger monooxygenases. Incubation of all of the cycloandrostane analogues resulted in lactonization of ring-D irrespective of C-6 stereochemistry or absence of C-3 functionality. Presence of 6beta-hydroxy group and the C-17 ketone was required in order for these analogues to undergo hydroxylation at C-15beta position. All metabolites were isolated by column chromatography and were identified by (1)H, (13)C NMR, DEPT analysis and other spectroscopic data. PMID- 26372081 TI - Are consumers aware of top-bottom but not of left-right inferences? Implications for shelf space positions. AB - We propose that the horizontal and vertical position of an item on a display is a source of information that individuals use to make judgments. Six experiments using 1 * 5 or 5 * 5 displays show that consumers judge that products placed at the bottom (vs. top) and on the left-hand (vs. middle and right-hand) side of a display are less expensive and of lower quality (Study 1a using a bar display, Study 1b using wine, and Study 1c using Swatch watches). Results support the claim that verticality effects (top-bottom) are attenuated when participants are less involved with the decision task (Study 2 using Swatch watches and chocolates) and when they are exposed to information that questions the diagnosticity of using vertical position as a cue (Study 3 using wine). However, the horizontality (left-right) effect is robust to both of these manipulations. Horizontality effects are exacerbated for participants primed with a number line (Study 4 also using wine), suggesting that exposure to the number line (where higher numbers are on the right) is a possible antecedent of the horizontality effect. The verticality effects may, on the other hand, reflect people's retail experience of seeing higher priced products on higher shelves, which leads to their forming a similar expectation. The paper concludes with a discussion of theoretical implications for visual information processing as well as practical implications for retail management. PMID- 26372082 TI - Leveraging the happy meal effect: Substituting food with modest nonfood incentives decreases portion size choice. AB - Despite much effort to decrease food intake by altering portion sizes, "super sized" meals are the preferred choice of many. This research investigated the extent to which individuals can be subtly incentivized to choose smaller portion sizes. Three randomized experiments (2 in the lab and 1 in the field) established that individuals' choice of full-sized food portions is reduced when they are given the opportunity to choose a half-sized version with a modest nonfood incentive. This substitution effect was robust across different nonfood incentives, foods, populations, and time. Experiment 1 established the effect with children, using inexpensive headphones as nonfood incentives. Experiment 2- a longitudinal study across multiple days--generalized this effect with adults, using the mere chance to win either gift cards or frequent flyer miles as nonfood incentives. Experiment 3 demonstrated the effect among actual restaurant customers who had originally planned to eat a full-sized portion, using the mere chance to win small amounts of money. Our investigation broadens the psychology of food portion choice from perceptual and social factors to motivational determinants. PMID- 26372083 TI - The first Early Career Psychiatrists' Fellowship Award of the Ain Shams International Congress on Psychiatry in Cairo, Egypt: Fostering International Collaboration on Education and Training. PMID- 26372084 TI - High serum testosterone levels during postpartum period are associated with postpartum depression. AB - In view of the reported cases of mood disorders that occur in mothers following childbirth and believing that sex steroid hormones contribute to mood and behavioral changes, this study has been aimed to explore the role of sex steroid hormones as an etiological factor for postpartum depression (PPD). This study was conducted at JIPMER, Puducherry, India between January 2010 and 2011. 103 women were recruited in the study after childbirth, out of which 62 women who were believed to be suffering from PPD were categorized as cases and the remaining 41 with no mood changes as controls, using Edinburgh Postpartum Depression Scale (EPDS) (cases had EPDS score >=10 at 24-28h, controls had score <10 at 24-48h postpartum). The hormones estimated in these two groups included estradiol, progesterone and testosterone, and their levels were compared between these two groups. A significantly high testosterone levels were observed in cases with PPD at 24-28h when compared to controls. Estradiol and progesterone levels did not show significant difference between cases and controls. ROC analysis done at 24 28h showed that testosterone levels beyond 42.71ng/mL predict the development of PPD with 79% sensitivity, 63% specificity, 68% positive predictive value, 74% negative predictive value with AUC being 0.708. This study shows that there is an association between persistent high serum testosterone level in women following childbirth and PPD. PMID- 26372085 TI - On oscillation reduction in feedback control for processes with an uncertain dead time and internal-external disturbances. AB - This paper aims to find a practical solution to reduce oscillation on the Smith Predictor (SP) based design with the dead time (DT) uncertainty, making it less sensitive to DT change and more effective in disturbance rejection. First, a conditional feedback mechanism is introduced in SP to reduce the amount of oscillation caused by the model inaccuracies in the DT parameter. Then, to address the oscillation caused by the phase lag in traditional PI controller and uncertain dynamics, this conditional SP is combined with active disturbance rejection control (ADRC), assisted by the knowledge of process dynamics. A practical tuning method is provided for the practicing engineers. The proposed approach is validated in extensive simulation studies with different types of plants and in frequency domain analysis. The simulation results show significant improvements in performance robustness and transient response. PMID- 26372086 TI - New Treatment Approaches for the Anemia of CKD. AB - Normocytic normochromic anemia is a common complication in chronic kidney disease and is associated with many adverse clinical consequences. Erythropoiesis stimulating agents (ESAs) and adjuvant iron therapy represent the primary treatment for anemia in chronic kidney disease. The introduction of ESAs into clinical practice was a success story, mediating an increase in hemoglobin concentrations without the risk for recurrent blood transfusions and improving quality of life substantially. However, recombinant ESAs are still expensive and require a parenteral route of administration. Moreover, concern has arisen following randomized clinical trials showing that higher hemoglobin targets and/or high ESA doses may cause significant harm. This, together with changes in ESA reimbursement policy in some countries, has resulted in a significant reduction in ESA prescribing and the hemoglobin level targeted during therapy. Several attempts are being made to develop new drugs with improved characteristics and/or easier manufacturing processes compared with currently available ESAs, including new treatment approaches that may indirectly improve erythropoiesis. We give an update on the new investigational strategies for increasing erythropoiesis, examining in depth their characteristics and possible advantages in the clinical setting and the caveats to be aware of at the present stage of development. PMID- 26372087 TI - Motivations, Challenges, and Attitudes to Self-management in Kidney Transplant Recipients: A Systematic Review of Qualitative Studies. AB - BACKGROUND: Kidney transplantation offers better outcomes compared to dialysis, but requires patients to adhere to an ongoing and complex self-management regimen. Medication nonadherence remains a leading cause of transplant loss, and inadequate self-management undermines transplantation and other health outcomes. We aimed to describe kidney transplant recipients' motivations, challenges, and attitudes toward self-management. STUDY DESIGN: Systematic review and thematic synthesis of qualitative studies. SETTING & POPULATION: Kidney transplant recipients. SEARCH STRATEGY & SOURCES: MEDLINE, EMBASE, PsycINFO, and CINAHL were searched to October 2014. ANALYTICAL APPROACH: Thematic synthesis. RESULTS: 50 studies involving 1,238 recipients aged 18 to 82 years across 19 countries were included. We identified 5 themes: empowerment through autonomy (achieving mastery, tracking against tangible targets, developing bodily intuition, routinizing and problem solving, and adaptive coping), prevailing fear of consequences (inescapable rejection anxiety, aversion to dialysis, minimizing future morbidity, trivialization and denial, and defining acceptable risks), burdensome treatment and responsibilities (frustrating ambiguities, inadvertent forgetfulness, intrusive side effects, reversing ingrained behaviors, and financial hardship), overmedicalizing life (dominating focus, evading patienthood, and succumbing to burnout), and social accountability and motivation (demonstrating gratitude toward medical team, indebtedness to donor, and peer learning). LIMITATIONS: Non-English articles were excluded. CONCLUSIONS: Self efficacy and social accountability are motivators for self-management, although adherence can be mentally and physically taxing. Multicomponent interventions incorporating personalized care planning, education, psychosocial support, decision aids, and self-monitoring tools may foster self-management capacity and improve transplantation outcomes. PMID- 26372088 TI - An internet survey of the characteristics and physical activity of community dwelling Australian adults with acquired brain injury: Exploring interest in an internet-delivered self-management program focused on physical activity. AB - BACKGROUND: Individuals with acquired brain injury (ABI) are more likely to be physically inactive and experience barriers to accessing services to address inactivity. This study was designed to guide the development of an internet delivered self-management program to increase physical activity after ABI. OBJECTIVE: The aims of this study were to examine the current physical activity status of community-dwelling Australian adults with ABI, the barriers to physical activity they experience and to explore interest an internet-delivered self management program aimed at increasing physical activity. METHODS: An online survey of Australian adults with ABI was used to collect information about demographic characteristics; general health; emotional well-being; mobility and physical activity status, and satisfaction; barriers to physical activity; confidence in overcoming barriers, and; interest in an internet self-management program. Data were analyzed descriptively and correlational analyses examined relationships between variables. RESULTS: Data were analyzed from 59 respondents. Over half were not satisfied with their current physical activity status. The most frequently reported barriers were pain/discomfort, fatigue and fear, and confidence to overcome these barriers was very low. Interest in an internet delivered self-management program was high (74%) and not related to the amount of physical activity, satisfaction with physical activity and mobility status or total number of barriers. CONCLUSION: Australian adults with ABI are not satisfied with their activity levels and experience barriers in maintaining their physical activity levels. Participants were interested in accessing an internet delivered self-management program aimed at improving physical activity levels. Therefore such a program warrants development and evaluation. PMID- 26372089 TI - P(?O)H to P-OH Tautomerism: A Theoretical and Experimental Study. AB - Phosphinylidene compounds R(1)R(2)P(O)H are important functionalities in organophosphorus chemistry and display prototropic tautomerism. Quantifying the tautomerization rate is paramount to understanding these compounds' tautomerization behavior, which may impact their reactivities in various reactions. We report a combined theoretical and experimental study of the initial tautomerization rate of a range of phosphinylidene compounds. Initial tautomerization rates are found to decrease in the order H3PO2 > Ph2P(O)H > (PhO)2P(O)H > PhP(O) (OAlk)H > AlkP(O)(OAlk)H ~ (AlkO)2P(O)H, where "Alk" denotes an alkyl substituent. The combination of computational investigations with experimental validation establishes a quantitative measure for the reactivity of various phosphorus compounds, as well as an accurate predictive tool. PMID- 26372090 TI - Zebrafish neurobehavioral phenomics for aquatic neuropharmacology and toxicology research. AB - Zebrafish (Danio rerio) are rapidly emerging as an important model organism for aquatic neuropharmacology and toxicology research. The behavioral/phenotypic complexity of zebrafish allows for thorough dissection of complex human brain disorders and drug-evoked pathological states. As numerous zebrafish models become available with a wide spectrum of behavioral, genetic, and environmental methods to test novel drugs, here we discuss recent zebrafish phenomics methods to facilitate drug discovery, particularly in the field of biological psychiatry. Additionally, behavioral, neurological, and endocrine endpoints are becoming increasingly well-characterized in zebrafish, making them an inexpensive, robust and effective model for toxicology research and pharmacological screening. We also discuss zebrafish behavioral phenotypes, experimental considerations, pharmacological candidates and relevance of zebrafish neurophenomics to other 'omics' (e.g., genomic, proteomic) approaches. Finally, we critically evaluate the limitations of utilizing this model organism, and outline future strategies of research in the field of zebrafish phenomics. PMID- 26372092 TI - Methionine-dependent histone methylation at developmentally important gene loci in mouse preimplantation embryos. AB - The involvement of specific nutrients in epigenetic gene regulation is a possible mechanism underlying nutrition-directed phenotypic alteration. However, the involvement of nutrients in gene-specific epigenetic regulation remains poorly understood. Methionine has been received attention as a possible nutrient involved in epigenetic modifications, as it is a precursor of the universal methyl donor for epigenetic methylation of DNA and histones. In the present study, the disruption of methionine metabolism by ethionine, an antimetabolite of methionine, induced abnormally higher expression of genes related to cell lineage differentiation and resulted in impaired blastocyst development of mouse preimplantation embryos in vitro. These effects were mitigated by the presence of methionine. Importantly, ethionine treatment induced lower trimethylation of histone H3 lysine 9 but did not affect methylation of DNA in the promoter regions of the examined genes. These results demonstrated that intact methionine metabolism is required for proper epigenetic histone modifications and normal expression of developmentally important genes during preimplantation development. PMID- 26372093 TI - Toward Anisotropic Hybrid Materials: Directional Crystallization of Amphiphilic Polyoxazoline-Based Triblock Terpolymers. AB - We present the design and synthesis of a linear ABC triblock terpolymer for the bottom-up synthesis of anisotropic organic/inorganic hybrid materials: polyethylene-block-poly(2-(4-(tert-butoxycarbonyl)amino)butyl-2-oxazoline)-block poly(2-iso-propyl-2-oxazoline) (PE-b-PBocAmOx-b-PiPrOx). The synthesis was realized via the covalent linkage of azide-functionalized polyethylene and alkyne functionalized poly(2-alkyl-2-oxazoline) (POx)-based diblock copolymers exploiting copper-catalyzed azide-alkyne cycloaddition (CuAAC) chemistry. After purification of the resulting triblock terpolymer, the middle block was deprotected, resulting in a primary amine in the side chain. In the next step, solution self-assembly into core-shell-corona micelles in aqueous solution was investigated by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Subsequent directional crystallization of the corona-forming block, poly(2-iso-propyl-2-oxazoline), led to the formation of anisotropic superstructures as demonstrated by electron microscopy (SEM and TEM). We present hypotheses concerning the aggregation mechanism as well as first promising results regarding the selective loading of individual domains within such anisotropic nanostructures with metal nanoparticles (Au, Fe3O4). PMID- 26372091 TI - Nutritional modulation of gut microbiota - the impact on metabolic disease pathophysiology. AB - The obesity epidemic afflicts over one third of the United States population. With few therapies available to combat obesity, a greater understanding of the systemic causes of this and other metabolic disorders is needed to develop new, effective treatments. The mammalian intestinal microbiota contributes to metabolic processes in the host. This review summarizes the research demonstrating the interplay of diet, intestinal microbiota and host metabolism. We detail the effects of diet-induced modifications in microbial activity and resultant impact on (1) sensory perception of macronutrients and total energy intake; (2) nutrient absorption, transport and storage; (3) liver and biliary function; (4) immune-mediated signaling related to adipose inflammation; and (5) circadian rhythm. We also discuss therapeutic strategies aimed to modify host microbe interactions, including prebiotics, probiotics and postbiotics, as well as fecal microbiota transplantation. Elucidating the role of gut microbes in shaping metabolic homeostasis or dysregulation provides greater insight into disease development and a promising avenue for improved treatment of metabolic dysfunction. PMID- 26372094 TI - Nanoporous block copolymer films using highly selective solvents and non-solvent extraction. AB - Nanoporous block copolymer thin films are fabricated by selective solvent swelling of the majority phase and subsequent rapid extraction with a miscible non-solvent (water). Selection of the initial solvent provides a facile route to tune the porosity of the films. Poly(butylnorbornene)-block poly(hydroxyhexafluoroisopropyl norbornene) (BuHFA) is used to generate these porous thin films due to its high Tg (>300 degrees C) and the selectivity of primary alcohols towards poly(hydroxyhexafluoroisopropyl norbornene) (pHFANB) to enable a relatively environmentally benign process. As the solvent quality for the HFA increases from ethanol to isopropanol to n-butanol, the porosity of the film developed by water extraction increases up to 69%. Aqueous mixtures of ethanol provide an addition handle to tune the porosity between 10 and 54%. These nanoporous films are robust with the porosity nearly unchanged after extended heating at 160 degrees C. Their elastic moduli are investigated using surface wrinkling and the modulus, E, scales with the film density, rho, as E ~ rho(2.2), which is similar to cellular solids. The nanopores are templated by the self assembled structure of the block copolymer, so these coatings are transparent despite the high porosity. These thin films act as anti-reflective coatings for glass slides. Spin coating provides a coating on both sides and processing to generate 55% porosity leads to an increase in transmittance from approximately 92% to 99.1% (average for the full range of visible light). A maximum transmittance of 99.8% is found at 523 nm. This methodology is simple and highly tunable; extension to other block copolymer systems is likely possible if sufficient solubility contrast between segments exists. PMID- 26372095 TI - Multi-liposomal containers. AB - Small unilamellar liposomes, 40-60 nm in diameter, composed of anionic diphosphatidylglycerol (cardiolipin, CL(2-)) or phosphatidylcerine (PS(1-)) and zwitter-ionic egg yolk lecithin (EL) or dipalmitoylphosphatidylcholine (DPPC), electrostatically complex with polystyrene microspheres, ca. 100 nm in diameter, grafted by polycationic chains ("spherical polycationic brushes", SPBs). Polymer/liposome binding studies were carried out using electrophoretic mobility (EPM), dynamic light scattering (DLS), fluorescence, conductometry, differential scanning calorimetry (DSC), and cryogenic transmission electron microscopy (cryo TEM) as the main analytical tools. By these means a remarkably detailed picture emerges of molecular events inside a membrane. The following are among the most important conclusions that arose from the experiments: (a) binding of liposomes to SPBs is accompanied by flip-flop of anionic lipids from the inner to the outer leaflet of the liposomal membrane along with lateral lipid segregation into "islands". (b) The SPB-induced structural reorganization of the liposomal membrane, together with the geometry of anionic lipid molecules, determines the maximum molar fraction of anionic lipid (a key parameter designated as nu) that ensures the structural integrity of liposomes upon complexation: nu=0.3 for liposomes with conically-shaped CL(2-) and nu=0.5 for liposomes with anionic cylindrically-shaped PS(1-). (c) The number of intact liposomes per SPB particle varies from 40 for (nu=0.1) to 13 (nu=0.5). (d) By using a mixture of liposomes with variety of encapsulated substances, multi-liposomal complexes can be prepared with a high loading capacity and a controlled ratio of the contents. (e) In order to make the mixed anionic liposomes pH-sensitive, they are additionally modified by 30 mol% of a morpholinocyclohexanol-based lipid that undergoes a conformational flip when changing pH. Being complexed with SPBs, such liposomes rapidly release their contents when the pH is reduced from 7.0 to 5.0. The results allow loaded liposomes to be concentrated within a rather small volume and, thereby, the preparation of multi-liposomal containers of promise in the drug delivery field. PMID- 26372097 TI - Distance from an Urban Sickle Cell Center and its Effects on Routine Healthcare Management and Rates of Hospitalization. AB - The St. Jude Children's Research Hospital (St. Jude) comprehensive sickle cell center serves a 150 mile catchment radius around Memphis, TN, USA. Full travel expenses are provided for routine and acute care visits for sickle cell disease patients living 35 miles from St. Jude. We compared hospitalization rates to national estimates and assessed if driving distance was a barrier to sickle cell healthcare despite the travel reimbursement policy. We evaluated the associations between hospitalizations and routine clinic visits and distance from St. Jude using negative binomial models and we conducted bias analyses by Monte Carlo simulation. We followed 545 patients (2550 patient-years) aged 18 years with sickle cell disease (Hb SS only) from 2007 to 2012. The hospitalization rate per patient-year was 0.65 [95% CI (confidence interval): 0.62, 0.68), significantly lower than the national rate of 1.16 (95% CI: 1.14, 1.18). Children living 5 35 miles from St. Jude had 1.75 (95% CI: 1.41, 2.17) times the rate of hospitalization and 1.22 (95% CI: 1.07, 1.39) times the rate of clinic visits compared to those 35 miles. Bias analysis suggested that under-reporting could explain the observed difference in hospitalization rates if 30.0% of patients who lived 35 miles from the hospital under-reported six hospitalizations over 6 years. The hospitalization rate at St. Jude in children with sickle cell disease was lower than expected from national rates. Greater distance from the sickle cell center (4 35 miles) was associated with decreased hospitalization rates, despite the travel allowances that are provided for those who live 35 miles from the hospital. PMID- 26372098 TI - Pretreatment Immune Parameters Predict for Overall Survival and Toxicity in Early Stage Non-Small-Cell Lung Cancer Patients Treated With Stereotactic Body Radiation Therapy. AB - INTRODUCTION: We determined whether pretreatment immunologic parameters could predict the outcomes and toxicity in early-stage non-small-cell lung cancer (NSCLC) patients treated with stereotactic body radiation therapy (SBRT). PATIENTS AND METHODS: The pretreatment leukocyte, lymphocyte, and neutrophil counts, serum albumin levels, neutrophil-to-lymphocyte ratio (NLR,) and platelet to-lymphocyte ratio (PLR) were evaluated to determine the association with locoregional control, distant metastasis-free survival (DMFS), disease-specific survival (DSS), overall survival (OS), and treatment-related toxicity. The survival rates were estimated with Kaplan-Meier analysis and multivariate analysis using the Cox proportional hazards model. RESULTS: The data from 118 patients with a median follow-up period of 28.9 months were assessed. The 3-year local control, regional control, and DMFS rates were 97%, 87%, and 92%, respectively. The 3-year OS and DSS rates were 77% and 85%, respectively. On univariate analysis, none of the pretreatment immune parameters predicted for disease control. A higher NLR (P = .008), PLR (P = .002), neutrophil count (P = .059), and the presence of lymphocytopenia (P = .032) independently prognosticated for poor OS. Receiver operating characteristic curve analysis found NLRs > 2.18 and PLRs > 187.27 optimally predicted for poor 3-year OS (P = .0262 and P = .0089, respectively). A higher NLR predicted against the development of any symptomatic toxicity and against the development of symptomatic (grade >= 2) radiation pneumonitis on univariate analysis, and a higher serum albumin level independently predicted for the development of symptomatic radiation pneumonitis (P = .0491). CONCLUSION: In the setting of SBRT, an elevated pretreatment NLR, PLR, and neutrophil count and the presence of lymphocytopenia independently predicted for poor OS. Patients who presented with higher NLRs and lower serum albumin levels experienced less treatment-related symptomatic toxicity. PMID- 26372099 TI - Stroke Risk Perception in Atrial Fibrillation Patients is not Associated with Clinical Stroke Risk. AB - BACKGROUND: Clinical risk stratification models, such as the CHA2DS2-VASc, are used to assess stroke risk in atrial fibrillation (AF) patients. No study has yet investigated whether and to which extent these patients have a realistic perception of their personal stroke risk. The purpose of this study was to investigate and describe the association between AF patients' stroke risk perception and clinical stroke risk. METHODS: In an observational cross-sectional study design, we surveyed 178 AF patients with a mean age of 70.6 years (SD 8.3) in stable anticoagulant treatment (65% treatment duration >12 months). Clinical stroke risk was scored through the CHA2DS2-VASc, and patients rated their perceived personal stroke risk on a 7-point Likert scale. RESULTS: There was no significant association between clinical stroke risk assessment and patients' stroke risk perception (rho = .025; P = .741). Approximately 60% of the high-risk patients had an unrealistic perception of their own stroke risk, and there was no significant increase in risk perception from those with a lower compared with a higher risk factor load (chi(2) = .010; P = .522). CONCLUSIONS: Considering possible negative implications in terms of lack of motivation for lifestyle behavior change and adequate adherence to the treatment and monitoring of vitamin K antagonist, the apparent underestimation of risk by large subgroups warrants attention and needs further investigation with regard to possible behavioral consequences. PMID- 26372100 TI - Association between Gamma-Glutamyltransferase Level and Risk of Stroke: A Systematic Review and Meta-analysis of Prospective Studies. AB - BACKGROUND: Stroke is often regulated by a number of modifiable and nonmodifiable risk factors. Recently, studies suggested high gamma-glutamyltransferase (GGT) level may be associated with stroke, but drew inconsistent conclusions. So, we conducted a meta-analysis to evaluate the relationship between GGT level and risk of stroke. METHODS: We systematically searched PubMed, Embase, and Cochrane Library (updated to January 2015) for prospective cohort studies. Then, relative risk (RR) with 95% confidence interval (CI) was used to assess the association. Regression analyses, subgroup analyses, and sensitivity analyses were also performed. The Begg test, Egger test, and the trim-and-fill method were used to assess potential publication bias. RESULTS: A total of 5707 cases and 926,497 participants in 10 prospective studies were included. Overall, high GGT level has a positive association with increased risk of stroke (RR = 1.28; 95% CI, 1.16 1.43). In the subgroup analyses, a positive association was consistently observed in each subgroup except in the women subgroup (RR = 1.45; 95% CI, .9-2.34) and a large number of stroke events subgroups (>= 500) (RR = 1.25; 95% CI, .85-1.84). Heterogeneity was significantly reduced in the subgroup analysis by population characteristics. In the publication bias test, the resulting adjusted RR remained significant (RR = 1.10; 95% CI, 1.00-1.21) after using the trim-and-fill method. CONCLUSIONS: Our meta-analysis provides evidence that a high level of GGT is significantly associated with increased risk of stroke independently of alcohol intake. Gender and ethnicity variations may exist in the relationship between high GGT level and risk of stroke. PMID- 26372102 TI - Corrigendum. AB - This article corrects: A distinct chemokine axis does not account for enrichment of Foxp3+ CD4+ T cells in carcinogen-induced fibrosarcomas. In Ontondo et al. 2015, errors have been identified in the Supporting Information Figure S1. The correct images of panels A and B are shown below.We apologize for this error. PMID- 26372101 TI - A Century of Germinal Matrix Intraventricular Hemorrhage in Autopsied Premature Infants: A Historical Account. AB - The care of premature infants in the 20th century is remarkable for technical advances that have dramatically improved survival, but little is known about temporal changes in the neuropathology of the premature infant over this time frame. We hypothesize that the autopsy rate of germinal matrix hemorrhage changed in the 20th century relative to combined influences of clinical interventions that were both harmful and helpful. We examined germinal matrix hemorrhage with intraventricular hemorrhage (GMH-IVH) in 345 premature infants (gestational age 25-36 weeks) autopsied at Boston Children's Hospital from 1914 to 2015. There was a median of 19 cases/decade (range 7-68). Over the course of the study median gestational age decreased from 33 to 27 gestational weeks (P<0.001), and median postnatal survival increased from 2 to 26 days (P=0.02). The incidence of GMH-IVH increased from 4.7% before 1960 to 50.0% from 1975 to 1980, and then decreased to 12.5% after 2005 (P<0.001). The incidence of GMH-IVH increased >3-fold around the time of the introduction of positive pressure ventilation into premature intensive care in the mid-1960s. The increased incidence of GMH-IVH in the 1970s 1980s likely reflects respiratory and hemodynamic imbalances complicating mechanical ventilation. We speculate that the subsequent decreased incidence of GMH-IVH likely reflects stabilization of respiratory function with improvements in ventilators and in ventilator management beginning in the 1970s and the use of surfactant and antenatal steroids in the 1980s. PMID- 26372103 TI - Genome-Wide Scan and Test of Candidate Genes in the Snail Biomphalaria glabrata Reveal New Locus Influencing Resistance to Schistosoma mansoni. AB - BACKGROUND: New strategies to combat the global scourge of schistosomiasis may be revealed by increased understanding of the mechanisms by which the obligate snail host can resist the schistosome parasite. However, few molecular markers linked to resistance have been identified and characterized in snails. METHODOLOGY/PRINCIPAL FINDINGS: Here we test six independent genetic loci for their influence on resistance to Schistosoma mansoni strain PR1 in the 13-16-R1 strain of the snail Biomphalaria glabrata. We first identify a genomic region, RADres, showing the highest differentiation between susceptible and resistant inbred lines among 1611 informative restriction-site associated DNA (RAD) markers, and show that it significantly influences resistance in an independent set of 439 outbred snails. The additive effect of each RADres resistance allele is 2-fold, similar to that of the previously identified resistance gene sod1. The data fit a model in which both loci contribute independently and additively to resistance, such that the odds of infection in homozygotes for the resistance alleles at both loci (13% infected) is 16-fold lower than the odds of infection in snails without any resistance alleles (70% infected). Genome-wide linkage disequilibrium is high, with both sod1 and RADres residing on haplotype blocks >2 Mb, and with other markers in each block also showing significant effects on resistance; thus the causal genes within these blocks remain to be demonstrated. Other candidate loci had no effect on resistance, including the Guadeloupe Resistance Complex and three genes (aif, infPhox, and prx1) with immunological roles and expression patterns tied to resistance, which must therefore be trans regulated. CONCLUSIONS/SIGNIFICANCE: The loci RADres and sod1 both have strong effects on resistance to S. mansoni. Future approaches to control schistosomiasis may benefit from further efforts to characterize and harness this natural genetic variation. PMID- 26372104 TI - Echogenic intracardiac focus on second trimester ultrasound: prevalence and significance in a Middle Eastern population. AB - OBJECTIVE: The association between echogenic intracardiac focus (EIF) and trisomy 21 is well established, with a recognized ethnic variation. Our study aimed to determine the prevalence of EIF in a Middle Eastern population and to examine its association with trisomy 21 and other adverse pregnancy outcomes. METHODS: Retrospective case-control study of second-trimester obstetric sonograms (16-28 weeks) performed at a tertiary care center over a 5-year period. Cases with EIF were retrieved, and a matched control group with no EIF was identified. The incidence of trisomy 21 and other adverse pregnancy outcomes was compared. RESULTS: A total of 9270 obstetric sonograms were examined, with an EIF prevalence of 2.5% (95% CI: 2.2-2.8%). Of patients with available outcome data, EIF was not associated with trisomy 21 (0/163 versus 1/163; p value = 1.00). Additionally, EIF was not associated with trisomy 18, trisomy 13, small for gestational age, preterm birth, fetal demise, cesarean delivery, operative vaginal delivery, or admission to the neonatal intensive care unit. CONCLUSION: In a contemporary Middle Eastern population, EIF is a rare occurrence. As an isolated finding, it is not associated with aneuploidy or other adverse pregnancy outcomes. EIF appears to be incidental with no impact on clinical practice. PMID- 26372105 TI - Common Traffic Violations of Bus Drivers in Urban China: An Observational Study. AB - OBJECTIVE: To report common traffic violations in bus drivers and the factors that influence those violations in urban China. METHODS: We conducted an observational study to record three types of traffic violations among bus drivers in Changsha City, China: illegal stopping at bus stations, violating traffic light signals, and distracted driving. The behaviors of bus drivers on 32 routes (20% of bus routes in the city) were observed. A two-level Poisson regression examined factors that predicted bus driver violations. RESULTS: The incidence of illegal stopping at bus stations was 20.2%. Illegal stopping was less frequent on weekends, sunny days, and at stations with cameras, with adjusted incidence rate ratios (IRRs) of 0.81, 0.65 and 0.89, respectively. The incidence of violating traffic light signals was 2.2%, and was lower on cloudy than sunny days (adjusted IRR: 0.60). The incidence of distracted driving was 3.3%. The incidence of distracted driving was less common on cloudy days, rainy or snowy days, and foggy/windy/dusty days compared to sunny days, with adjusted IRRs of 0.54, 0.55 and 0.07, respectively. CONCLUSION: Traffic violations are common in bus drivers in urban China and they are associated with the date, weather, and presence of traffic cameras at bus station. Further studies are recommended to understand the behavioral mechanisms that may explain bus driver violations and to develop feasible prevention measures. PMID- 26372106 TI - Reduced Fitness of Virulent Aphis glycines (Hemiptera: Aphididae) Biotypes May Influence the Longevity of Resistance Genes in Soybean. AB - Sustainable use of insect resistance in crops require insect resistance management plans that may include a refuge to limit the spread of virulence to this resistance. However, without a loss of fitness associated with virulence, a refuge may not prevent virulence from becoming fixed within a population of parthenogenetically reproducing insects like aphids. Aphid-resistance in soybeans (i.e., Rag genes) prevent outbreaks of soybean aphid (Aphis glycines), yet four biotypes defined by their capacity to survive on aphid-resistant soybeans (e.g., biotype-2 survives on Rag1 soybean) are found in North America. Although fitness costs are reported for biotype-3 on aphid susceptible and Rag1 soybean, it is not clear if virulence to aphid resistance in general is associated with a decrease in fitness on aphid susceptible soybeans. In laboratory assays, we measured fitness costs for biotype 2, 3 and 4 on an aphid-susceptible soybean cultivar. In addition, we also observed negative cross-resistance for biotype-2 on Rag3, and biotype-3 on Rag1 soybean. We utilized a simple deterministic, single-locus, four compartment genetic model to account for the impact of these findings on the frequency of virulence alleles. When a refuge of aphid susceptible was included within this model, fitness costs and negative cross-resistance delayed the increase of virulence alleles when virulence was inherited recessively or additively. If virulence were inherited additively, fitness costs decreased the frequency of virulence. Combined, these results suggest that a refuge may prevent virulent A. glycines biotypes from overcoming Rag genes if this aphid-resistance were used commercially in North America. PMID- 26372107 TI - Interaction of vitamin B1 with bovine serum albumin investigation using vitamin B1-selective electrode: potentiometric and molecular modeling study. AB - Vitamin B1 or thiamin is one of the B vitamins. All B vitamins help the body to convert food (carbohydrates) into fuel (glucose), which produces energy. The B vitamins are necessary for healthy skin, eyes, hair, and liver. It also could help the nervous system function properly, and is necessary for brain functions. Drug interactions with protein can affect the distribution of the drug and eliminate the drug in living systems. In this study, the binding of thiamine hydrochloride (vitamin B1) to bovine serum albumin (BSA) was evaluated using a new proposed vitamin B1 (thiamine)-selective membrane electrode under various experimental conditions, such as pH, ionic strength, and protein concentration; in addition molecular modeling was applied as well. The binding isotherms plotted based on potentiometric data and analyzed using the Wyman binding potential concept. The apparent binding constant was determined and used for the calculation of intrinsic Gibbs free energy of binding. According to the electrochemical and molecular docking results, it can be concluded that the hydrophobic interactions and hydrogen binding are major interactions between BSA and vitamin B1. PMID- 26372108 TI - Early Training-Induced Reduction of Angiotensinogen in Autonomic Areas-The Main Effect of Exercise on Brain Renin-Angiotensin System in Hypertensive Rats. AB - BACKGROUND: Exercise training (T) blunts functional deficits and renin angiotensin system (RAS) hyperactivity in hypertensive individuals. There is no information on T-induced temporal changes of brain RAS. We evaluate now the simultaneous effects of T on functional responses and time course changes in the expression/activity of brain RAS components in autonomic cardiovascular controlling areas. METHODS AND RESULTS: Spontaneously hypertensive rats (SHR) and age-matched normotensive controls (WKY) were trained for 0, 1, 2, 4, 8 and 12 weeks. Sedentary (S) groups served as time-controls. After arterial pressure (AP) and heart rate (HR) recordings at rest, fresh and fixed brains were harvested for qPCR and immunofluorescence assays. SHR-S vs. WKY-S exhibited higher mean AP (MAP) and HR, increased pressure variability and sympathetic activity, elevated AT1 receptor (AT1) expression in nucleus tractus solitarii (NTS) and higher Mas receptor expression in the rostroventrolateral medulla (RVLM). In SHR, T promptly (T2 on) reduced sympathetic variability to heart/vessels and largely decreased angiotensinogen expression in the paraventricular hypothalamic nucleus (PVN) and NTS, with a late RVLM reduction (T4). AT1 expression was only reduced at T12 (PVN and NTS) with transient, not maintained Mas receptor changes in PVN and RVLM. These responses were accompanied by baseline MAP and HR reduction in the SHR-T (from T4 on). In the SHR group, PVN angiotensinogen expression correlated positively with sympathetic activity, resting MAP and HR. In WKY-T, a precocious (T2-T12) RVLM AT1 decrease preceded the appearance of resting bradycardia (from T8 on). CONCLUSIONS: Early and maintained reduction of angiotensinogen content in autonomic areas of the SHR is the most prominent effect of training on brain RAS. Down-regulation of PVN RAS expression is an essential factor to drive cardiovascular benefits in SHR-T, while resting bradycardia in WKY-T is correlated to RVLM AT1 reduction. PMID- 26372110 TI - Antibacterial, antifungal and antimycobacterial activities of some pyrazoline, hydrazone and chalcone derivatives. AB - Twenty-seven previously reported chalcones and their pyrazoline and hydrazone derivatives as well as two further chalcones have been screened for their antimicrobial, antifungal and antimycobacterial activities against standard microbial strains and drug resistant isolates. The minimum inhibitory concentration (MIC) value of each compound was determined by a two-fold serial microdilution technique. The compounds were found to possess a broad spectrum of antimicrobial activities with MIC values of 8-128 MUg/mL. One compound [(E)-1-(4 hydroxyphenyl)-3-p-tolylprop-2-en-1-one] had equal activity with gentamycin (8 MUg/mL) against Enterococcus faecalis. Chalcones were found to be more active than their hydrazone and 2-pyrazoline derivatives against Staphylococcus aureus ATCC 29213 and E. faecalis ATCC 29212. PMID- 26372109 TI - Electromagnetic hypersensitivity--an increasing challenge to the medical profession. AB - BACKGROUND: In 1970, a report from the former Soviet Union described the "microwave syndrome" among military personnel, working with radio and radar equipment, who showed symptoms that included fatigue, dizziness, headaches, problems with concentration and memory, and sleep disturbances. Similar symptoms were found in the 1980s among Swedes working in front of cathode ray tube monitors, with symptoms such as flushing, burning, and tingling of the skin, especially on the face, but also headaches, dizziness, tiredness, and photosensitivity. The same symptoms are reported in Finns, with electromagnetic hypersensitivity (EHS) being attributed to exposure to electromagnetic fields (EMF). Of special concern is involuntary exposure to radiofrequency (RF)-EMF from different sources. Most people are unaware of this type of exposure, which has no smell, color, or visibility. There is an increasing concern that wireless use of laptops and iPads in Swedish schools, where some have even abandoned textbooks, will exacerbate the exposure to EMF. METHODS: We have surveyed the literature on different aspects of EHS and potential adverse health effects of RF-EMF. This is exemplified by case reports from two students and one teacher who developed symptoms of EHS in schools using Wi-Fi. RESULTS: In population-based surveys, the prevalence of EHS has ranged from 1.5% in Sweden to 13.3% in Taiwan. Provocation studies on EMF have yielded different results, ranging from where people with EHS cannot discriminate between an active RF signal and placebo, to objectively observed changes following exposure in reactions of the pupil, changes in heart rhythm, damage to erythrocytes, and disturbed glucose metabolism in the brain. The two students and the teacher from the case reports showed similar symptoms, while in school environments, as those mentioned above. DISCUSSION: Austria is the only country with a written suggestion to guidelines on the diagnosis and treatment of EMF-related health problems. Apart from this, EHS is not recognized as a specific diagnosis in the rest of the world, and no established treatment exists. CONCLUSION: It seems necessary to give an International Classification of Diseases to EHS to get it accepted as EMF-related health problems. The increasing exposure to RF-EMF in schools is of great concern and needs better attention. Longer-term health effects are unknown. Parents, teachers, and school boards have the responsibility to protect children from unnecessary exposure. PMID- 26372111 TI - Oropharyngeal trauma mimicking a first branchial cleft anomaly. AB - We present a unique and challenging case of a remnant foreign body that presented to us in a child disguised as a strongly suspected congenital branchial cleft anomaly. This case entailed oropharyngeal trauma, with a delayed presentation as a retroauricular cyst accompanied by otorrhea that mimicked the classic presentation of an infected first branchial cleft anomaly. During surgical excision of the presumed branchial anomaly, a large wooden stick was found in the tract. The diagnostic and therapeutic obstacles in the management of such cases are highlighted. In addition to exploring the existing literature, we retrospectively analyzed a plausible explanation of the findings of this case. Laryngoscope, 126:E224-E226, 2016. PMID- 26372112 TI - Dynamics of career choice among students in undergraduate medical courses. A BEME systematic review: BEME Guide No. 33. AB - INTRODUCTION: Due to the lack of a theoretically embedded overview of the recent literature on medical career decision-making, this study provides an outline of these dynamics. Since differences in educational routes to the medical degree likely affect career choice dynamics, this study focuses on medical career decision-making in educational systems with a Western European curriculum structure. METHODS: A systematic search of electronic databases (Medline, Embase) was conducted from January 2008 to November 2014. A panel of seven independent reviewers performed the data extraction, quality assessment and data synthesis using the Bland-Meurer model of medical specialty choice as a reference. RESULTS: Fifty-seven studies met the inclusion criteria for the review. Factors associated with specialty preference or career choice can be classified in five main categories: (1) medical school characteristics (e.g., curriculum structure), (2) student characteristics (e.g., age, personality), (3) student values (e.g., personal preference), (4) career needs to be satisfied (e.g., expected income, status, and work-life balance), and (5) perception of specialty characteristics (e.g., extracurricular or curricular experiences). Especially career needs and perceptions of specialty characteristics are often associated with medical career decision-making. CONCLUSION: Our results support that medical career decisions are formed by a matching of perceptions of specialty characteristics with personal needs. However, the process of medical career decision-making is not yet fully understood. Besides identifying possible predictors, future research should focus on detecting interrelations between hypothesized predictors and identify the determinants and interrelations at the various stages of the medical career decision-making process. PMID- 26372113 TI - "Why can't I give you my organs after my heart has stopped beating?" An overview of the main clinical, organisational, ethical and legal issues concerning organ donation after circulatory death in Italy. AB - Donation after circulatory death (DCD) is a valuable option for the procurement of functioning organs for transplantation. Clinical results are promising and public acceptance is quite good in most western countries. Yet, although DCD is widespread in Europe, several problems still persist in Italy as well as in some other countries. This paper aims to describe the main clinical, organisational, ethical and legal issues at stake, bearing in mind the particular situation created by Italian legislation. Currently, as regards DCD, Italy is somewhat different from other countries. Therefore, every effort should be made for the safe and effective implementation of DCD programs: uncontrolled DCD programs should be promoted and encouraged, within the framework of shared and authoritative rules. At the same time, we need to tackle the question of controlled DCD, promoting debate among all involved subjects regarding the fundamental issues of end-of-life care within protocols that best integrate the highest standard of care for the dying and the legitimate interests of those awaiting a life-saving organ. PMID- 26372114 TI - Cerebral vasospasm after traumatic brain injury: an update. AB - BACKGROUND: Post-traumatic vasospasm (PTV) remains a poorly understood entity. Using a systematic review approach, we examined the incidence, mechanisms, risk factors, impact on outcome and potential therapies of PTV. METHODS: A search on Medline database up to 2015 performed with "traumatic brain injury" and "vasospasm" key-words retrieved 429 references. This systematic review was reported and analysed following the PRISMA criteria and according to the relevance in human clinical practice. RESULTS: The research retrieved 429 references of which 226 were excluded from analysis because of their irrelevance and 87 finally included in the review. CONCLUSION: Mechanical stretching, inflammation, calcium dysregulation, endotelin, contractile proteins, products of cerebral metabolism and cortical spreading depolarization have been involved in PTV pathophysiology. PTV occurs in up to 30-40% of the patients after severe traumatic brain injury. Usually, PTV starts within the first 3 days following head trauma and may last 5 to 10 days. Young age, low Glasgow Coma Score at admission and subarachnoid hemorrhage have been identified as risk factors of PTV. Suspected on transcranial Doppler, PTV diagnosis is best confirmed by angiography, CT angiography or MR angiography, and perfusion and ischaemic consequences by perfusion CT or MRI. Early PTV is associated with poor outcome. No PTV prevention strategy has proved efficient up to now. Regarding PTV treatment, only nimodipine and intra-arterial papaverine have been studied up to now. Treatment with milrinone has been described in a few cases reports and may represent a new therapeutic option. PMID- 26372115 TI - Carbapenemase-producing Klebsiella pneumoniae with two different gene expression patterns. PMID- 26372116 TI - Noninvasive Assessment of Carotid Pulse Pressure Values: An Accelerometric-Based Approach. AB - OBJECTIVE: Central pulse pressure (cPP) is increasingly investigated as possible independent predictor of cardiovascular risk and carotid pulse pressure (carPP) can be used as a surrogate of cPP. Despite its importance, carPP measurement remains challenging in clinical practice. The aim of this study was to introduce a new easier-to-use method for noninvasive carPP evaluation based on the use of a MEMS accelerometer. METHODS: carPP values (carPP(acc)) were obtained in 22 subjects (10 males, 47 +/-17 years, hypertension: 50%) postprocessing and double integrating the accelerometric signals. carPP(acc) measurements were compared with tonometric assessments (carPP(ton)), and ultrasound-derived measurements (carPP(us)). Moreover, accelerometric carotid pressure waveforms (P(acc)) were contrasted in terms of shape to those obtained by tonometry (P(ton)) and ultrasound images elaboration (P(US)), calculating the root mean square error (RMSE(ton), RMSE(US)) and the regression coefficients (r(ton) and r(US)). Moreover, both the repeatability and reproducibility analyses were performed. RESULTS: carPP(acc) values (45.9 +/-10.6 mmHg) were significantly correlated with carPP(ton) (47.5 +/-11.3 mmHg) and carPP(US) (43.3 +/-8.4 mmHg) assessments (R = 0.94, p < 0.0001 and R = 0.80, p < 0.0001, respectively). The validity of the accelerometric approach was confirmed by morphological parameters ( RMSE(ton) = 5 +/-1.95 mmHg, RMSE(US) = 5.5 +/-2.3 mmHg, r(ton) = 0.94 +/-0.04, r(US) = 0.93 +/ 0.04). Coefficient of variation (CV) was equal to 6.2% for the repeatability analysis, while CV values for interoperator and intersession reproducibilities were 8.9% and 9.4%, respectively. CONCLUSION: The proposed approach, providing an easier and more available measurement, could represent a valid alternative to existing and used technique for carPP assessment. PMID- 26372117 TI - Pairwise Latent Semantic Association for Similarity Computation in Medical Imaging. AB - Retrieving medical images that present similar diseases is an active research area for diagnostics and therapy. However, it can be problematic given the visual variations between anatomical structures. In this paper, we propose a new feature extraction method for similarity computation in medical imaging. Instead of the low-level visual appearance, we design a CCA-PairLDA feature representation method to capture the similarity between images with high-level semantics. First, we extract the PairLDA topics to represent an image as a mixture of latent semantic topics in an image pair context. Second, we generate a CCA-correlation model to represent the semantic association between an image pair for similarity computation. While PairLDA adjusts the latent topics for all image pairs, CCA correlation helps to associate an individual image pair. In this way, the semantic descriptions of an image pair are closely correlated, and naturally correspond to similarity computation between images. We evaluated our method on two public medical imaging datasets for image retrieval and showed improved performance. PMID- 26372118 TI - Eina! Ouch! Eish! Professionals' Perceptions of How Children with Cerebral Palsy Communicate About Pain in South African School Settings: Implications for the use of AAC. AB - Most children with severe cerebral palsy experience daily pain that affects their school performance. School professionals need to assess pain in these children, who may also have communication difficulties, in order to pay attention to the pain and support the children's continued participation in school. In this study, South African school professionals' perceptions of how they observed pain in children with cerebral palsy, how they questioned them about it and how the children communicated their pain back to them were investigated. Thirty-eight school professionals participated in five focus groups. Their statements were categorized using qualitative content analysis. From the results it became clear that professionals observed children's pain communication through their bodily expressions, behavioral changes, and verbal and non-verbal messages. Augmentative and alternative communication (AAC) methods were rarely used. The necessity of considering pain-related vocabulary in a multilingual South African context, and of advocating for the use of AAC strategies to enable children with cerebral palsy to communicate their pain was highlighted in this study. PMID- 26372119 TI - Allometric growth in the extant coelacanth lung during ontogenetic development. AB - Coelacanths are lobe-finned fishes known from the Devonian to Recent that were long considered extinct, until the discovery of two living species in deep marine waters of the Mozambique Channel and Sulawesi. Despite extensive studies, the pulmonary system of extant coelacanths has not been fully investigated. Here we confirm the presence of a lung and discuss its allometric growth in Latimeria chalumnae, based on a unique ontogenetic series. Our results demonstrate the presence of a potentially functional, well-developed lung in the earliest known coelacanth embryo, and its arrested growth at later ontogenetic stages, when the lung is clearly vestigial. The parallel development of a fatty organ for buoyancy control suggests a unique adaptation to deep-water environments. Furthermore, we provide the first evidence for the presence of small, hard, flexible plates around the lung in L. chalumnae, and consider them homologous to the plates of the 'calcified lung' of fossil coelacanths. PMID- 26372121 TI - Reconstruction of a Complex Auricular Defect. PMID- 26372122 TI - Quantitative Evaluation of Female Pattern Hair Loss in Chinese Women: A Preliminary Study. AB - BACKGROUND: The common grading systems for female pattern hair loss (FPHL), such as Ludwig and Savin scales, are subjective to visual inspection. To provide a more objective evaluation of baldness, the authors have developed a method to calculate baldness quantitatively through a computer-aided imaging system (CAIS). OBJECTIVE: To investigate the use of CAIS on Chinese women with FPHL. MATERIALS AND METHODS: Thirty-eight Chinese women with FPHL (Savin Scale I-2 to II-2) were recruited. A total of 215 photographs were taken. The central balding areas (CBAs) were calculated after exposure correction by CAIS for comparison with clinical staging. RESULTS: The average CBA was 9,391.12 mm in all patients, 3,828.84 mm in Type I-2, 5,880.38 mm in I-3, 8,267.44 mm in I-4, 12,999.26 mm in II-1, and 15,979.71 mm in II-2. The values of CBA correlated with clinical staging using Savin scales. A 7.53% difference was found in the calculated CBA by exposure correction. CONCLUSION: The CAIS allows physicians to evaluate the severity of baldness more accurately through quantitative calculation, rather than qualitative visual observation. The values of the CBA measured by the CAIS, used in conjunction with the present grading systems, may be more precise and efficient to evaluate the severity of FPHL. PMID- 26372123 TI - Lymph Node Metastasis in Cutaneous Head and Neck Squamous Cell Carcinoma. AB - BACKGROUND: Cutaneous squamous cell carcinoma (CSCC), the second most common cancer in whites, may result in nodal metastasis in 4% of patients. In the last decade, sentinel lymph node biopsy (SLNB) became the common practice for treating patients with invasive skin cancers such as melanoma, although its use in patients with CSCC is still under debate. OBJECTIVE: To find the rate of cervical lymph node metastasis in the series of patients with CSCC of the head and neck and to identify those who may need SLNB. MATERIALS AND METHODS: A retrospective data collection on all patients diagnosed with CSCC of head and neck during the years 1998 to 2005. RESULTS: A total of 572 patients with 725 head and neck CSCC were included in the study group. During the follow-up period, 10 (1.3%) patients developed lymph node metastases and no patient developed distant metastases. The probability of lymph node metastasis within 6 years for T1 and T2 tumors was 1.09% and 5.46%, respectively (p = .0387). CONCLUSION: Because of the relatively low incidence of cervical lymph node metastases in patients with CSCC of the head and neck, SLNB for clinically N0 patients is not justified. PMID- 26372120 TI - Empirically based comparisons of the reliability and validity of common quantification approaches for eyeblink startle potentiation in humans. AB - Startle potentiation is a well-validated translational measure of negative affect. Startle potentiation is widely used in clinical and affective science, and there are multiple approaches for its quantification. The three most commonly used approaches quantify startle potentiation as the increase in startle response from a neutral to threat condition based on (1) raw potentiation, (2) standardized potentiation, or (3) percent-change potentiation. These three quantification approaches may yield qualitatively different conclusions about effects of independent variables (IVs) on affect when within- or between-group differences exist for startle response in the neutral condition. Accordingly, we directly compared these quantification approaches in a shock-threat task using four IVs known to influence startle response in the no-threat condition: probe intensity, time (i.e., habituation), alcohol administration, and individual differences in general startle reactivity measured at baseline. We confirmed the expected effects of time, alcohol, and general startle reactivity on affect using self-reported fear/anxiety as a criterion. The percent-change approach displayed apparent artifact across all four IVs, which raises substantial concerns about its validity. Both raw and standardized potentiation approaches were stable across probe intensity and time, which supports their validity. However, only raw potentiation displayed effects that were consistent with a priori specifications and/or the self-report criterion for the effects of alcohol and general startle reactivity. Supplemental analyses of reliability and validity for each approach provided additional evidence in support of raw potentiation. PMID- 26372124 TI - Ashland Block, the Schiller Building, and Chicago's Post-Graduate School of Anaesthesia. PMID- 26372125 TI - Fanny Davenport and the Doctors Rugg: 25-cent "Extracting, with Gas". PMID- 26372126 TI - Dame Cicely Courtneidge's 1931 "Laughing Gas" Recording. PMID- 26372127 TI - A Different Perspective on Transfusion Requirements in Surgical Oncology Patients. PMID- 26372128 TI - Association of Postoperative Transfusion Strategy with Short-term Outcomes in Surgical Oncology Patients. PMID- 26372129 TI - Adding a New Piece to the Transfusion Puzzle in Oncologic Surgery Patients. PMID- 26372130 TI - Transfusion Threshold Trials: The Need to Establish a Clear Difference in Transfusion Practice between Study Groups. PMID- 26372131 TI - Liberal Transfusion Practice or Perioperative Treatment of Anemia to Avoid Transfusion? PMID- 26372132 TI - In Reply. PMID- 26372133 TI - Heparin for Cardiac Surgery: Old and Forgotten? PMID- 26372134 TI - In Reply. PMID- 26372135 TI - Occupational Hazards of Exposure to Magnetic Resonance Imaging. PMID- 26372136 TI - In Reply. PMID- 26372137 TI - Suboptimal Protocol? PMID- 26372138 TI - In Reply. PMID- 26372144 TI - Neosaxitoxin versus Traditional Local Anesthetics: Mechanism of Action and Sites of Notable Effect. PMID- 26372145 TI - Characterisation of a Novel Anti-CD52 Antibody with Improved Efficacy and Reduced Immunogenicity. AB - Anti-CD52 therapy has been shown to be effective in the treatment of a number of B cell malignancies, hematopoietic disorders and autoimmune diseases (including rheumatoid arthritis and multiple sclerosis); however the current standard of treatment, the humanized monoclonal antibody alemtuzumab, is associated with the development of anti-drug antibodies in a high proportion of patients. In order to address this problem, we have identified a novel murine anti-CD52 antibody which has been humanized using a process that avoids the inclusion within the variable domains of non-human germline MHC class II binding peptides and known CD4+ T cell epitopes, thus reducing its potential for immunogenicity in the clinic. The resultant humanized antibody, ANT1034, was shown to have superior binding to CD52 expressing cells than alemtuzumab and was more effective at directing both antibody dependent and complement dependent cell cytotoxicity. Furthermore, when in the presence of a cross-linking antibody, ANT1034 was more effective at directly inducing apoptosis than alemtuzumab. ANT1034 also showed superior activity in a SCID mouse/human CD52 tumour xenograft model where a single 1 mg/Kg dose of ANT1034 led to increased mouse survival compared to a 10 mg/Kg dose of alemtuzumab. Finally, ANT1034 was compared to alemtuzumab in in vitro T cell assays in order to evaluate its potential to stimulate proliferation of T cells in peripheral blood mononuclear cells derived from a panel of human donors: whereas alemtuzumab stimulated proliferation in a high proportion of the donor cohort, ANT1034 did not stimulate proliferation in any of the donors. Therefore we have developed a candidate therapeutic humanized antibody, ANT1034, that may have the potential to be more efficacious and less immunogenic than the current standard anti-CD52 therapy. PMID- 26372146 TI - Cost-effectiveness analysis of neurocognitive-sparing treatments for brain metastases. AB - BACKGROUND: Decisions regarding how to treat patients who have 1 to 3 brain metastases require important tradeoffs between controlling recurrences, side effects, and costs. In this analysis, the authors compared novel treatments versus usual care to determine the incremental cost-effectiveness ratio from a payer's (Medicare) perspective. METHODS: Cost-effectiveness was evaluated using a microsimulation of a Markov model for 60 one-month cycles. The model used 4 simulated cohorts of patients aged 65 years with 1 to 3 brain metastases. The 4 cohorts had a median survival of 3, 6, 12, and 24 months to test the sensitivity of the model to different prognoses. The treatment alternatives evaluated included stereotactic radiosurgery (SRS) with 3 variants of salvage after recurrence (whole-brain radiotherapy [WBRT], hippocampal avoidance WBRT [HA WBRT], SRS plus WBRT, and SRS plus HA-WBRT). The findings were tested for robustness using probabilistic and deterministic sensitivity analyses. RESULTS: Traditional radiation therapies remained cost-effective for patients in the 3 month and 6-month cohorts. In the cohorts with longer median survival, HA-WBRT and SRS plus HA-WBRT became cost-effective relative to traditional treatments. When the treatments that involved HA-WBRT were excluded, either SRS alone or SRS plus WBRT was cost-effective relative to WBRT alone. The deterministic and probabilistic sensitivity analyses confirmed the robustness of these results. CONCLUSIONS: HA-WBRT and SRS plus HA-WBRT were cost-effective for 2 of the 4 cohorts, demonstrating the value of controlling late brain toxicity with this novel therapy. Cost-effectiveness depended on patient life expectancy. SRS was cost-effective in the cohorts with short prognoses (3 and 6 months), whereas HA WBRT and SRS plus HA-WBRT were cost-effective in the cohorts with longer prognoses (12 and 24 months). PMID- 26372147 TI - Correlation of vestibular aqueduct size with air-bone gap in enlarged vestibular aqueduct syndrome. AB - OBJECTIVES/HYPOTHESIS: Patients with enlarged vestibular aqueduct (EVA) often demonstrate an air-bone gap (ABG) at low frequencies on audiometric testing. The mechanism for this has not been well elucidated. We investigated vestibular aqueduct (VA) size and ABG in patients with EVA, and assessed the relationship between VA diameter and ABG. STUDY DESIGN: Retrospective review. METHODS: We assessed 98 ears from 49 individuals diagnosed with Pendred syndrome. The VA diameters of ears in groups with (n = 60) and without (n = 38) ABG were measured using axial computed tomography images. Three different parameters of VA diameter (fundus, midpoint, and porous width) were correlated with the results of pure tone analysis. RESULTS: We found that patients with ABG have larger diameters of the VA than patients without ABG (fundus width = 1.13 vs. 0.71 mm, respectively; midpoint width = 3.23 vs. 2.77 mm, respectively; porous width = 2.73 vs. 2.29 mm, respectively; P < .001, .038, and .049, respectively). A cutoff value of VA fundus diameter was set at 0.865 mm. Although <5% of the variability in the ABG was explainable by variation in the diameter of the VA fundus at low frequencies, on average, larger gaps were observed with fundus diameters of >0.865 mm. CONCLUSIONS: Our findings suggest that the axial parameters of the VA yield information about ABG in patients with EVA. The data are consistent with the hypothesis that an EVA introduces a third mobile window into the inner ear, resulting in an ABG at low frequencies. LEVEL OF EVIDENCE: 4. Laryngoscope, 126:1633-1638, 2016. PMID- 26372148 TI - Scleral Flap-Everting Suture for Glaucoma-filtering Surgery. AB - PURPOSE: Most filtering surgery failures develop in the early postoperative period. The possibility to apply an everting suture to lift the flap in the postoperative period and reduce the possibility of an early failure is reported. METHODS: Surgical technique description. RESULTS: An everting suture may be applied to the scleral flap in all types of ab externo anterior filtering surgeries. It could allow the surgeon to lift the scleral flap after the removal of the releasable sutures. CONCLUSIONS: The use of an everting suture would eliminate the need to use procedures for lifting the flap that involve puncturing the conjunctiva and may cause hemorrhages and leakage and promote scarring. PMID- 26372149 TI - Deep Sclerectomy With Mitomycin C and Injectable Cross-linked Hyaluronic Acid Implant: Long-term Results. AB - PURPOSE: To evaluate the long-term efficacy and safety of deep sclerectomy (DS) augmented with mitomycin C (MMC) and injectable cross-linked hyaluronic acid implant (Healaflow) in medically refractory glaucoma patients. MATERIALS AND METHODS: Our study included 96 eyes of 83 consecutive patients with open-angle glaucoma undergoing MMC-DS with injectable cross-linked hyaluronic acid implant. Mean follow-up was 28.6+/-20.0 months. Variables analyzed were: intraocular pressure (IOP), best-corrected visual acuity, mean number of antiglaucomatous drugs, execution of postoperative maneuvres (goniopuncture, bleb needling, and laser lysis of scleral flap sutures). Tonometric success was defined by 2 different thresholds, specifically IOP<=21 mm Hg (criterion A) and <=15 mm Hg (criterion B). The procedure was defined as a qualified success if reached with medication and as a complete success if reached without. RESULTS: For criterion A, qualified and complete success rates were 96% and 94%, respectively, at 12 months, 95% and 92% at 24 months, and 92% and 89% at 36 months. For criterion B, qualified and complete success rates were 75% and 75%, respectively, at 12 months, 62% and 60% at 24 months, and 59% and 58% at 36 months. Goniopuncture was performed in 56 eyes (58%), bleb needling with 5-fluorouracil injection in 4 eyes (5.1%), and laser release of scleral flap sutures in 4 eyes (4%). Six eyes required additional filtering surgery. CONCLUSION: DS with Healaflow and MMC seems to be an effective and safe technique to lower IOP in patients affected by open-angle glaucoma, with few postoperative complications. PMID- 26372150 TI - Evaluation of Blebs After Filtering Surgery With En-Face Anterior-Segment Optical Coherence Tomography: A Pilot Study. AB - PURPOSE: To compare characteristics of functioning blebs (FBs) and nonfunctioning blebs (NFBs) with en-face spectral-domain optical coherence tomography (OCT). METHODS: We evaluated 41 blebs of 38 patients after a first-time trabeculectomy. Eyes were classified into 2 groups: FBs (22 eyes) and NFBs (19 eyes). En-face OCT images were analyzed semiquantitatively for the density of intraepithelial microcysts (0 to 3), internal fluid-filled cavity (0 to 3), and bleb vascularization (0 to 2). Presence of conjunctival fibrosis and visualization of the scleral flap were also analyzed. RESULTS: FBs showed significantly more intraepithelial microcysts than did NFBs: the mean grading of microcyst density was 1.86 for FBs and 0.11 for NFBs (P<0.0001). None of the FBs were rated 0 and none of the NFBs were rated 2 or 3 for the density of intraepithelial microcysts. NFBs presented more conjunctival fibrosis than FBs (63% vs. 32%, P<0.05). There was no significant difference between FBs and NFBs for bleb vascularization, visualization of the scleral flap, and presence of subepithelial fluid-filled cavities. There was a direct correlation between postoperative intraocular pressure and intraepithelial microcyst density (r=-0.7655, P<0.0001). The long term administration of preserved eyedrops before surgery was associated with fewer intraepithelial microcysts (r=-0.5436; P=0.0006). CONCLUSIONS: FBs were associated with a higher number of intraepithelial microcysts evaluated with en face OCT. A higher density of microcysts was associated with a lower intraocular pressure and a shorter duration of preserved topical treatment before surgery. En face OCT provides a simple, noninvasive, and reproducible method to analyze blebs after filtering surgery. PMID- 26372151 TI - A Novel Method for the Delivery of Antimetabolites During Glaucoma Surgery. AB - Current techniques for the delivery of antimetabolites, such as mitomycin C, tend to be very variable among surgeons and risk uncontrolled contact with the conjunctivae, which may result in delayed wound healing, wound dehiscence, and wound leakage postoperatively. We describe a novel technique which appear to allow a more precise and reproducible delivery of antimetabolite to the target area with minimal contact with the conjunctival edge. The technique involves the injection of an antimetabolite-soaked wick into the subconjunctival space posterior to the scleral flap using an intraocular lens injector system. PMID- 26372152 TI - Outcomes of Trabeculectomy With Transconjunctival Application Versus Subconjunctival Application of Mitomycin C. AB - PURPOSE: To compare outcomes and complication rates of trabeculectomy with either transconjunctival mitomycin C (MMC) or subconjunctival MMC application. METHODS: Retrospective cohort study-35 eyes in subconjunctival group and 29 eyes in transconjunctival group. All surgeries were performed by 1 surgeon (E.A.) at 1 center with an average follow-up duration of 40 to 51 months. RESULTS: The mean percentage intraocular pressure reduction at final follow-up was with 44.4+/ 25.3% reduction in the subconjunctival group compared with 48.0+/-24.6% reduction in the transconjunctival group, with no statistical significant difference between the 2 groups (P=0.57). Both groups also showed a >40% reduction in intraocular pressure in approximately 67% of eyes. There were no cases of endophthalmitis. There was 1 reported case of choroidal hemorrhage following subconjunctival application of MMC. There were similar low rates of postoperative bleb leakage and requirement for postoperative application of 5-fluorouracil. There was a greater incidence of hyphema in the subconjunctival group (5 vs. 1) as well as choroidal effusions (8 vs. 4). One patient underwent revision of trabeculectomy and this was in the subconjunctival group. CONCLUSION: Transconjunctival application of MMC offers a safe and effective method of performing trabeculectomy with adjunctive MMC with lower rates of complication than subconjunctival application. PMID- 26372153 TI - Flow Test to Predict Early Hypotony and Hypertensive Phase After Ahmed Glaucoma Valve (AGV) Surgical Implantation. AB - PURPOSE: To assess the validity of a preimplantation flow test to predict early hypotony [intraocular pressure (IOP)<=5 mm Hg on 2 consecutive visits and hypertensive phase (HP) (IOP>21 mm Hg) after Ahmed Glaucoma Valve (AGV) implantation. PATIENTS AND METHODS: Prospective interventional study on patients receiving an AGV. A preimplantation flow test using a gravity-driven reservoir and an open manometer was performed on all AGVs. Opening pressure (OP) and closing pressure (CP) were defined as the pressure at which fluid was seen to flow or stop flowing through the AGV, respectively. OP and CP were measured twice per AGV. Patients were followed for 12 weeks. RESULTS: In total, 20 eyes from 19 patients were enrolled. At 12 weeks the mean IOP decreased from 29.2+/-9.1 to 16.8+/-5.2 mm Hg (P<0.01). The mean AGV OP was 17.5+/-5.4 mm Hg and the mean CP was 6.7+/-2.3 mm Hg. Early (within 2 wk postoperative) HP occurred in 37% and hypotony in 16% of cases. An 18 mm Hg cutoff for the OP gave a sensitivity of 0.71, specificity of 0.83, positive predictive value of 0.71, and negative predictive value of 0.83 for predicting an early HP. A 7 mm Hg cutoff for the CP yielded a sensitivity of 1.0, specificity of 0.38, positive predictive value of 0.23, and negative predictive value of 1.0 for predicting hypotony. CONCLUSIONS: Preoperative OP and CP may predict early hypotony or HP and may be used as a guide as to which AGV valves to discard before implantation surgery. PMID- 26372154 TI - To Study the Efficacy of Laser Peripheral Iridoplasty in the Treatment of Eyes With Primary Angle Closure and Plateau Iris Syndrome, Unresponsive to Laser Peripheral Iridotomy, Using Anterior-Segment OCT as a Tool. AB - PURPOSE: To use anterior-segment optical coherence tomography (AS-OCT) as a tool to monitor the outcome of iridoplasty in patients with primary angle closure (PAC) and plateau iris syndrome (PIS), who were unresponsive to a previous laser peripheral iridotomy. MATERIALS AND METHODS: This was a prospective, observational case control study. Patients diagnosed with PAC and PIS who had undergone laser peripheral iridotomy earlier, but were unresponsive to the procedure, were subjected to an iridoplasty. The intraocular pressure (IOP) and anterior-chamber parameters were measured before and after the procedure, and complications were noted. The patients were followed up for 1 year, and results were analyzed. RESULTS: Twenty-four eyes of 12 patients underwent the iridoplasty procedure. Sixteen eyes were diagnosed as cases of PAC and 8 eyes were diagnosed as cases of PIS. Main outcome measures were the IOP, peripheral anterior synechiae, AS-OCT angle parameters, and complications. After iridoplasty, there was a significant decrease in the IOP from 24.4+/-5.6 to 16.5+/-5.4 mm Hg (P<0.001) at the final follow-up. The mean number of antiglaucoma medications decreased from 1.6+/-0.9 to 0.7+/-1.1. The medians of the peripheral anterior synechiae extent reduced from 3.5 (quartile range, 1.5 to 6.0) to 2.0 (quartile range, 0.5 to 4.0) clock hours in the PAC group (P<0.001) and from 3.8 (quartile range, 2.0 to 6.5) to 2.5 (quartile range, 0.8 to 5.0) clock hours in the PIS group (P<0.001). Changes in AS-OCT parameters noted were as follows: the AOD500 increased from 0.132+/-0.016 to 0.179+/-0.062 mm (P<0.001), TISA500 from 0.085+/ 0.012 to 0.104+/-0.051 mm (P<0.001), and scleral spur angle from 19.5+/-2.4 to 26.8+/-4.5 degrees (P<0.001). No significant changes in the angle-to-angle distance and the crystalline lens rise were found. CONCLUSIONS: In eyes with synechial angle closure and PIS that do not show an improvement after an iridotomy, laser peripheral iridoplasty can be very effective. There were no significant complications after the iridoplasty procedure, implying that it is quite safe. This study also demonstrates that AS-OCT can serve as a useful tool to document the preprocedure angle parameters, to note the changes after the procedure, and for the long-term follow-up of these patients. PMID- 26372155 TI - The Frequency of Optical Coherence Tomography Testing in Glaucoma at a Single Academic Medical Center. AB - PURPOSE: To determine the frequency of optical coherence tomography (OCT) examinations compared with clinical examinations and visual field (VF) tests in patients with 5 types of glaucoma. PATIENTS AND METHODS: A retrospective, longitudinal cohort study was conducted of 5154 patients treated between 2003 and 2010 at a single academic medical center. Patients were classified using billing records as having primary open-angle glaucoma, low-tension open-angle glaucoma (NTG), pigmentary open-angle glaucoma, chronic angle-closure glaucoma, or pseudoexfoliation glaucoma. Analysis of variance, chi test, and exact chi test were performed to identify associations between glaucoma type and test frequency. RESULTS: Pigmentary open-angle glaucoma and NTG patients had a higher rate of undergoing at least 2 VFs (94.4%, 94.9%), and chronic angle-closure glaucoma patients had a lower rate of undergoing at least 2 OCTs (25.3%) than all other glaucoma types. NTG patients also had the highest rate of undergoing at least 2 OCTs and at least 2 VFs (36.6%). Overall, the rate of clinical examinations (2.68 examinations/y) exceeded the rates of OCTs (1.39 examinations/y), which exceeded the rate of VF tests (1.24 tests/y). There were no differences in OCT frequency between glaucoma types (0.91 to 1.63 OCTs/y). Within each glaucoma diagnosis, patients had clinical examinations more frequently than OCTs and clinical examinations more frequently than VFs. Primary open-angle glaucoma and pseudoexfoliation glaucoma patients also had OCTs more frequently than VFs. More patients had at least 2 VF tests than at least 2 OCTs (4481 vs. 1679). CONCLUSION: The relative use of clinical examinations, VF testing, and OCT imaging varies among glaucoma diagnoses. PMID- 26372156 TI - Cost-Utility Analysis of Cataract Surgery in Advanced Glaucoma Patients. AB - PURPOSE: To assess the cost-effectiveness of cataract surgery in advanced glaucoma (AG) patients. MATERIALS AND METHODS: A total of 93 patients with AG who underwent cataract surgeries were collected prospectively from June 2010 through June 2013 in Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai, and were followed up for at least 3 months. A standard phacoemulsification technique was used to remove cataract(s). No complications occurred intraoperatively or postoperatively. Costs associated with surgery were recorded. Utility values of cataract surgery were obtained by using time trade off method. Quality-adjusted life-years (QALYs) were calculated using the patients' life expectancy at a 3% discounted rate. Incremental cost-utility analysis was performed (compared with no treatment) by calculating the incremental cost-effectiveness ratio (ICER), that is, the mean incremental cost for each QALY. The bootstrap method was used for statistical analysis, and sensitivity analyses were performed to test robustness of the results. RESULTS: The mean incremental cost of cataract surgery was 9876 Chinese yuan (CNY) [1593 US dollar (USD)] [95% confidence interval (CI), 9144-10,570 CNY (1475-1705 USD)].The mean additional QALYs gained were 2.20 (95% CI, 1.85-2.54), and the incremental cost for each additional QALY was 4508 CNY (727 USD) [95% CI, 3890 5234 CNY (627-844 USD)], far lower than the per capita annual disposable income in Shanghai, 40,188 CNY (6482 USD). CONCLUSION: For AG patients, cataract surgery does help obtain more QALYs and was highly cost effective. PMID- 26372157 TI - Reproducibility of Circumpapillary Retinal Nerve Fiber Layer Thickness Measurements Evaluated by Circle and Annulus Area With and Without Correction for Ocular Rotation. AB - PURPOSE: To compare the reproducibility of annulus area measurements of the circumpapillary retinal nerve fiber layer thickness (cpRNFLTannulus) using spectral-domain optical coherence tomography (SD-OCT) with that of conventional cpRNFLT (cpRNFLTring) measurements and evaluate the effect of correction of ocular rotation on the reproducibility. MATERIALS AND METHODS: Peripapillary SD OCT raster scans were performed on 2 different days in 48 normal subjects and 59 patients with glaucoma using the Topcon OCT-1000. In the raster scan dataset, the cpRNFLTring and cpRNFLTannulus were averaged along a circle (3.4-mm diameter) and in an annulus area (diameters from 2.8 to 4.0 mm) centered on the barycenter of the disc. The measurement reproducibility, effects of ocular rotational correction, and factors affecting the reproducibility were studied. RESULTS: The intervisit reproducibility values, expressed as the coefficients of variation, for the cpRNFLTannulus, were significantly smaller than those for the cpRNFLTring measurements in sectors 30 degrees wide in glaucomatous eyes (P=0.006) and in sectors 10 degrees wide in normal and glaucomatous eyes (P<0.001). The ocular rotational angles averaged 7.1 and 7.2 degrees with intervisit differences of 1.4 and 1.8 degrees, respectively, in normal and glaucomatous eyes. Correction for the ocular rotation had little effect on the reproducibility. The mean deviation and cpRNFLT were correlated negatively with the coefficient of variation (beta= 0.93 to -0.83; P=0.027 to 0.028). CONCLUSIONS: The cpRNFLTannulus measurement yielded better reproducibility than the cpRNFLTring measurement, and multiple linear regression analysis showed that the more advanced the glaucomatous damage, the worse the intervisit reproducibility. PMID- 26372158 TI - Evaluation of Carotid Intima Media Thickness and Renal Artery Resistive Index in Patients With Pseudoexfoliation Syndrome: A Prospective Case-Control Study. AB - PURPOSE: To investigate the significance of renal artery resistance and carotid intima media thickness (CIMT) parameters in patients with pseudoexfoliation syndrome (PES). MATERIALS AND METHODS: In this prospective case-control study, 37 patients were involved and grouped as PES (n=19) and control groups (n=18). Ophthalmological evaluation included visual acuity, intraocular pressure, central corneal thickness measurement, and optic disc evaluation. In addition, renal artery resistive index and CIMT measurements were taken for all patients and compared between the groups. RESULTS: The 2 groups were similar with respect to age, sex, and family history of glaucoma. The mean CIMT in the PES group was found to be significantly higher compared with the control group (0.73+/-0.02 vs. 0.59+/-0.06 mm, P=0.003). Renal artery resistive indices were found to be higher in the PES group than in the control group, however, the difference was not significant (P=0.46). A moderate positive correlation between CIMT and renal artery resistive indices was detected (r=0.447, P=0.01). However, a higher correlation rate was detected when the analysis was made in the PES group only (r=0.603, P=0.01). CONCLUSIONS: CIMT increases in PES patients and also the renal artery resistance index has a tendency to increase. Patients with PES should be informed about potential systemic consequences of this syndrome. PMID- 26372159 TI - Complex nontuberculous mycobacterial cervicofacial lymphadenitis: What is the optimal approach? AB - OBJECTIVES/HYPOTHESIS: Assess the role of combined antimicrobial and surgical therapy for difficult-to-treat nontuberculous mycobacteria (NTM) lesions of the head and neck in children. STUDY DESIGN: Retrospective cohort. METHODS: Retrospective review of pediatric head and neck NTM lesions at a tertiary children's hospital from 1999 to 2012. RESULTS: Seventy-one children were diagnosed with NTM lesions. Age of presentation ranged between 7 and 204 months of age. Most patients (62%) had multiple lesions. Treatments included incision and drainage, curettage, antibiotics, excision, and any combination of surgery and antibiotics. Upon initial presentation, the most common treatment was surgical excision alone (n = 34) with a high complication rate (50%). In 18 cases, patients were initially treated with a combination of antibiotics and surgical excision due to the extent or location of the lesion(s). Complication rate in these patients was also high (67%). The most common complications in surgically excised NTM lesions included temporary or persistent facial nerve dysfunction (24.6%), poor wound healing/scarring (10.8%), and Frey's syndrome (6.2%). CONCLUSIONS: Surgical excision with or without medical therapy for NTM cervicofacial lymphadenitis in high-risk regions commonly resulted in marginal mandibular nerve dysfunction (24.6%). Postoperative facial nerve weakness generally resolved within a year. High rates of complications and a lack of proven best approaches suggest tailoring the approach to address the potential risks in that particular patient based on location and severity. LEVEL OF EVIDENCE: 4 Laryngoscope, 126:1677-1680, 2016. PMID- 26372160 TI - Technology Resource, Distribution, and Development Characteristics of Global Influenza Virus Vaccine: A Patent Bibliometric Analysis. AB - Influenza virus vaccine (IVV) is a promising research domain that is closely related to global health matters, which has been acknowledged not only by scientists and technology developers, but also by policy-makers. Meanwhile, patents encompass valuable technological information and reflect the latest technological inventions as well as the innovative capability of a nation. However, little research has examined this up-and-coming research field using patent bibliometric method. Thus, this paper (a) designs the technology classification system and search strategy for the identification of IVV; and (b) presents a longitudinal analysis of the global IVV development based on the European Patent Office (EPO) patents. Bibliometric analysis is used to rank countries, institutions, inventors and technology subfields contributing to IVV technical progress. The results show that the global trends of IVV are a multi developing feature of variety but an uneven technical resource distribution. Although the synthetic peptide vaccine is a comparatively young field, it already demonstrates the powerful vitality and the enormous development space. With the worldwide competition increasing, all nations especially China should be looking to increase devotion, enhance capability and regard effectiveness of technological innovation. PMID- 26372161 TI - A Novel Aldo-Keto Reductase (AKR17A1) of Anabaena sp. PCC 7120 Degrades the Rice Field Herbicide Butachlor and Confers Tolerance to Abiotic Stresses in E. coli. AB - Present study deals with the identification of a novel aldo/keto reductase, AKR17A1 from Anabaena sp. PCC7120 and adds on as 17th family of AKR superfamily drawn from a wide variety of organisms. AKR17A1 shares many characteristics of a typical AKR such as- (i) conferring tolerance to multiple stresses like heat, UV B, and cadmium, (ii) excellent activity towards known AKR substrates (isatin and 2-nitrobenzaldehyde), and (iii) obligate dependence on NADPH as a cofactor for enzyme activity. The most novel attribute of AKR17A1, first reported in this study, is its capability to metabolize butachlor, a persistent rice field herbicide that adversely affects agro-ecosystem and non-target organisms. The AKR17A1 catalyzed- degradation of butachlor resulted into formation of 1,2 benzene dicarboxylic acid and 2,6 bis (1,1, dimethylethyl) 4,-methyl phenol as the major products confirmed by GC-MS analysis. PMID- 26372163 TI - Micropatterned Surfaces for Atmospheric Water Condensation via Controlled Radical Polymerization and Thin Film Dewetting. AB - Inspired by an example found in nature, the design of patterned surfaces with chemical and topographical contrast for the collection of water from the atmosphere has been of intense interest in recent years. Herein we report the synthesis of such materials via a combination of macromolecular design and polymer thin film dewetting to yield surfaces consisting of raised hydrophilic bumps on a hydrophobic background. RAFT polymerization was used to synthesize poly(2-hydroxypropyl methacrylate) (PHPMA) of targeted molecular weight and low dispersity; spin-coating of PHPMA onto polystyrene films produced stable polymer bilayers under appropriate conditions. Thermal annealing of these bilayers above the glass transition temperature of the PHPMA layer led to complete dewetting of the top layer and the formation of isolated PHPMA domains atop the PS film. Due to the vastly different rates of water nucleation on the two phases, preferential dropwise nucleation of water occurred on the PHPMA domains, as demonstrated by optical microscopy. The simplicity of the preparation method and ability to target polymers of specific molecular weight demonstrate the value of these materials with respect to large-scale water collection devices or other materials science applications where patterning is required. PMID- 26372164 TI - Nanorecycling: Monolithic Integration of Copper and Copper Oxide Nanowire Network Electrode through Selective Reversible Photothermochemical Reduction. AB - Laser induced selective photothermochemical reduction is demonstrated to locally and reversibly control the oxidation state of Cu and Cu oxide nanowires in ambient conditions without any inert gas environment. This new concept of "nanorecycling" can monolithically integrate Cu and Cu oxide nanowires by restoring oxidized Cu, considered unusable for the electrode, back to a metallic state for repetitive reuse. PMID- 26372162 TI - Changes in Serum Free Amino Acids and Muscle Fatigue Experienced during a Half Ironman Triathlon. AB - The aim of this study was to investigate the relationship between changes in serum free amino acids, muscle fatigue and exercise-induced muscle damage during a half-ironman triathlon. Twenty-six experienced triathletes (age = 37.0 +/- 6.8 yr; experience = 7.4 +/- 3.0 yr) competed in a real half-ironman triathlon in which sector times and total race time were measured by means of chip timing. Before and after the race, a countermovement jump and a maximal isometric force test were performed, and blood samples were withdrawn to measure serum free amino acids concentrations, and serum creatine kinase levels as a blood marker of muscle damage. Total race time was 320 +/- 37 min and jump height (-16.3 +/- 15.2%, P < 0.001) and isometric force (-14.9 +/- 9.8%; P = 0.007) were significantly reduced after the race in all participants. After the race, the serum concentration of creatine kinase increased by 368 +/- 187% (P < 0.001). In contrast, the serum concentrations of essential (-27.1 +/- 13.0%; P < 0.001) and non-essential amino acids (-24.4 +/- 13.1%; P < 0.001) were significantly reduced after the race. The tryptophan/BCAA ratio increased by 42.7 +/- 12.7% after the race. Pre-to-post changes in serum free amino acids did not correlate with muscle performance variables or post-race creatine kinase concentration. In summary, during a half-ironman triathlon, serum amino acids concentrations were reduced by > 20%. However, neither the changes in serum free amino acids nor the tryptophan/BCAA ratio were related muscle fatigue or muscle damage during the race. PMID- 26372165 TI - Perception of Esthetic Impact of Smile Line in Complete Denture Wearers by Different Age Groups. AB - PURPOSE: To evaluate esthetic perceptions based on tooth exposure when smiling of patients wearing complete dentures by evaluators in different age groups. MATERIALS AND METHODS: Alterations were made to a front view photograph of a smiling patient wearing complete maxillary and mandibular dentures. Alterations in the smile line were simulated to increase or decrease tooth exposure (increments of 0.5 mm). For this purpose, image manipulation software was used. After manipulation, images were printed on photo paper, attached to a questionnaire, and distributed to individuals in three age groups (n = 150). To evaluate the esthetic perception for each image, a visual analog scale was used, with 0 representing least attractive, 5 representing attractive, and 10 representing very attractive. Differences between examiners were analyzed using the Mann-Whitney test. All statistical analyses were performed with a degree of confidence of 95%. RESULTS: Two evaluators did not observe any differences between images. The images given the best and worst scores were E and O (alterations of 2 and 7 mm), respectively, in the 15- to 19-year-old group, B and O (alterations of 0.5 and 7 mm), respectively, in the 35- to 44-year-old group, and A and M (no alteration and 6 mm alteration), respectively, in the 65- to 74 year-old group. When the images were presented together (images 1 and 2), the unaltered image was selected by individuals of different age groups as the best, and the image with a change of 7 mm was selected as the worst. CONCLUSION: In this study, complete dental prostheses with smile lines that coincided with the cervical margins of the anterior teeth were the most acceptable. Less exposure of the maxillary teeth when smiling corresponded with decreased attractiveness. PMID- 26372166 TI - Structural Bridges through Fold Space. AB - Several protein structure classification schemes exist that partition the protein universe into structural units called folds. Yet these schemes do not discuss how these units sit relative to each other in a global structure space. In this paper we construct networks that describe such global relationships between folds in the form of structural bridges. We generate these networks using four different structural alignment methods across multiple score thresholds. The networks constructed using the different methods remain a similar distance apart regardless of the probability threshold defining a structural bridge. This suggests that at least some structural bridges are method specific and that any attempt to build a picture of structural space should not be reliant on a single structural superposition method. Despite these differences all representations agree on an organisation of fold space into five principal community structures: all-alpha, all-beta sandwiches, all-beta barrels, alpha/beta and alpha + beta. We project estimated fold ages onto the networks and find that not only are the pairings of unconnected folds associated with higher age differences than bridged folds, but this difference increases with the number of networks displaying an edge. We also examine different centrality measures for folds within the networks and how these relate to fold age. While these measures interpret the central core of fold space in varied ways they all identify the disposition of ancestral folds to fall within this core and that of the more recently evolved structures to provide the peripheral landscape. These findings suggest that evolutionary information is encoded along these structural bridges. Finally, we identify four highly central pivotal folds representing dominant topological features which act as key attractors within our landscapes. PMID- 26372167 TI - Implications of genetics and current protected areas for conservation of 5 endangered primates in China. AB - Most of China's 24-28 primate species are threatened with extinction. Habitat reduction and fragmentation are perhaps the greatest threats. We used published data from a conservation genetics study of 5 endangered primates in China (Rhinopithecus roxellana, R. bieti, R. brelichi, Trachypithecus francoisi, and T. leucocephalus); distribution data on these species; and the distribution, area, and location of protected areas to inform conservation strategies for these primates. All 5 species were separated into subpopulations with unique genetic components. Gene flow appeared to be strongly impeded by agricultural land, meadows used for grazing, highways, and humans dwellings. Most species declined severely or diverged concurrently as human population and crop land cover increased. Nature reserves were not evenly distributed across subpopulations with unique genetic backgrounds. Certain small subpopulations were severely fragmented and had higher extinction risk than others. Primate mobility is limited and their genetic structure is strong and susceptible to substantial loss of diversity due to local extinction. Thus, to maximize preservation of genetic diversity in all these primate species, our results suggest protection is required for all sub populations. Key priorities for their conservation include maintaining R. roxellana in Shennongjia national reserve, subpopulations S4 and S5 of R. bieti and of R. brelichi in Fanjingshan national reserve, subpopulation CGX of T. francoisi in central Guangxi Province, and all 3 T. leucocephalus sub-populations in central Guangxi Province. PMID- 26372168 TI - Refractive indices of unfilled resin mixtures and cured composites related to color and translucency of conventional and low-shrinkage composites. AB - This study correlated the refractive indices (RIs) of unfilled resin mixtures and resin-based composites (RBCs) with color and translucency of conventional and low shrinkage RBCs. Unfilled resin mixtures based on different ratios of conventional monomers Bisphenol A-glycidyl-methacrylate (BisGMA)/triethyleneglycol dimethacrylate (TEGDMA) and urethane-dimethacrylate (UDMA)/TEGDMA and a low shrinkage monomer FIT-852 (FIT, Esstech Inc.)/TEGDMA were used to prepare model RBCs, containing 30 wt % of the organic matrix and 70 wt % of silanated barium glass fillers (n = 1.553, Esstech Inc.). The RIs of resins were measured on an ABBE refractometer, those of cured RBCs using the Becke-line method in immersion oils. Color and translucency were determined using an AvaSpec-2048 (Avantes BV) spectrometer. The RIs of unfilled resin mixtures decreased with increasing amounts of TEGDMA. Cured RBCs had higher RIs than their respective resin mixtures. BisGMA-based composites were more translucent with significantly lower L* values than FIT- and UDMA-based RBCs. The RIs of unfilled resins positively correlated with cured RBCs (p = 0.001), as did the RIs with translucency (p = 0.001) and color (p = 0.008). Resin mixtures and corresponding RBCs based on UDMA and its modified low-shrinkage version, FIT, showed similar optical properties. The RIs of unfilled resins appeared to be good predictors of the RIs of cured RBCs. (c) 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 7-13, 2017. PMID- 26372169 TI - Doped quantum dot@silica nanocomposites for white light-emitting diodes. AB - This work reports the use of a near-UV-LED chip in combination with blue, green yellow and red emitting doped ZnSe QD@silica nanocomposites to construct a novel WLED with reduced scattering and no reabsorption. Blue, green-yellow and red emitting Cu or Mn doped ZnSe QDs with enlarged Stokes shifts and similar absorption peaks (360-410 nm) were synthesized in liquid paraffin in order to solve the reabsorption problem and also obtain balanced white emission spectra. Silica shells were then coated onto the doped QDs, allowing for the refractive index of the nanocomposites to be tailored while simultaneously improving their compatibility with the epoxy resin. The transparent doped ZnSe QD@SiO2/epoxy composite was then used as a light conversion and encapsulant material in combination with the near-UV-LED chip to fabricate the WLED. This fabricated WLED demonstrated high luminous efficiency and good color chromatics stability, suggesting that WLEDs based on highly fluorescent doped ZnSe QD@silica nanocomposites in combination with near-UV-LED chips may prove to be promising candidates for alternative light sources. PMID- 26372170 TI - Synthesis of spiro[2.5]octa-4,7-dien-6-one with consecutive quaternary centers via 1,6-conjugate addition induced dearomatization of para-quinone methides. AB - An efficient one-pot approach for the synthesis of spiro[2.5]octa-4,7-dien-6-ones by employing para-quinone methides has been developed. The reaction proceeded smoothly in high yields under mild conditions without the use of metals. Moreover, all products obtained herein contained two or three consecutive quaternary centers. PMID- 26372171 TI - Superior Antibacterial Activity of Fe3O4-TiO2 Nanosheets under Solar Light. AB - Fe3O4-TiO2 nanosheets (Fe3O4-TNS) were synthesized by means of lamellar reverse micelles and solvothermal method, which were characterized by TEM, XRD, XPS, BET, and magnetic property analysis. It can be found that Fe3O4-TNS nanosheets exhibited better photocatalytic antibacterial activity toward Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus than pure Fe3O4 and TNS, and the antibacterial efficiency could reach 87.2% and 93.7% toward E. coli and S. aureus with 100 MUg/mL Fe3O4-TNS after 2 h of simulated solar light illumination, respectively. The photocatalytic destruction of bacteria was further confirmed by fluorescent-based cell live/dead test and SEM images. It was uncovered that Fe3O4-TNS inactivated G- E. coli and G+ S. aureus by different mechanisms: the destruction of outer membranes and ruptured cell bodies were responsible for the bactericidal effect against E. coli, while the antibacterial effect toward S. aureus were due to the fact that the cells were adsorbed in form of clusters by massive Fe3O4-TNS, which could restrict their activities and cause malfunction of the selective permeable barriers. Furthermore, the antibacterial mechanism was studied by employing scavengers to understand exact roles of different reactive species, indicating the key roles of h(+) and H2O2. The recovery and reusability experiments indicated that Fe3O4-TNS still retained more than 90% bacteria removal efficiency even after five cycles. Considering the easy magnetic separation, bulk availability, and high antibacterial activity of Fe3O4 TNS, it is a promising candidate for cleaning the microbial contaminated water environment. PMID- 26372172 TI - Thermal conductivity of zinc blende and wurtzite CdSe nanostructures. AB - Many binary octet compounds including CdSe can be grown in either the wurtzite (WZ) or zinc blende (ZB) phase, which has aroused great interest among the research community in understanding the phase dependence of the thermal transport properties of these compounds. So far, it has been debatable whether the ZB phase possesses higher thermal conductivity than the WZ phase. In this work, we report on thermal conductivity measurements of CdSe nanowires/nanoribbons with both WZ and ZB phases via a suspended device method. At room temperature, the thermal conductivity of all the ZB CdSe nanostructures measured in this work is higher than the bulk thermal conductivity of the WZ CdSe reported in the literature, suggesting that the bulk thermal conductivity of the ZB CdSe is higher than that of the WZ phase. Our result is different from previous experimental results in the literature for InAs nanowires which suggest similar thermal conductivity values for the bulk ZB and WZ InAs crystals. The higher thermal conductivity of the ZB CdSe can be explained by its lower anharmonicity and a smaller number of atoms per unit cell compared to the WZ phase. PMID- 26372173 TI - Current Magnitude and Mechanisms of Groundwater Discharge in the Arctic: Case Study from Alaska. AB - To better understand groundwater-surface water dynamics in high latitude areas, we conducted a field study at three sites in Alaska with varying permafrost coverage. The natural groundwater tracer ((222)Rn, radon) was used to evaluate groundwater discharge, and electrical resistivity tomography (ERT) was used to examine subsurface mixing dynamics. Different controls govern groundwater discharge at these sites. In areas with sporadic permafrost (Kasitsna Bay), the major driver of submarine groundwater discharge is tidal pumping, due to the large tidal oscillations, whereas at Point Barrow, a site with continuous permafrost and small tidal amplitudes, fluxes are mostly affected by seasonal permafrost thawing. Extended areas of low resistivity in the subsurface alongshore combined with high radon in surface water suggests that groundwater surface water interactions might enhance heat transport into deeper permafrost layers promoting permafrost thawing, thereby enhancing groundwater discharge. PMID- 26372174 TI - Research and publishing. PMID- 26372175 TI - Solid-Sampling Electrothermal Vaporization Inductively Coupled Plasma Optical Emission Spectrometry for Direct Determination of Total Oxygen in Coal. AB - A new analytical method for direct determination of total oxygen contents in eight coal samples of the Argonne Premium Coal (APC) series and in the NIST SRM 1632d is presented. The development of a suitable calibration procedure, optimization of measurement conditions, and the application of a tailored data processing for handling of plasma effects and high blanks enable the quantification of oxygen simultaneously with other trace, minor, or major elements in whole coal samples by means of electrothermal vaporization inductively coupled plasma optical emission spectrometry (ETV-ICP OES). For comparison, the oxygen contents were determined by a direct oxygen analyzer. The obtained oxygen values of the APC and the reference material NIST SRM 1632d were compared to data in the literature. The precision of the ETV-ICP OES was within +/-3.5%, and the recovery better than 92%. With this good accuracy, the developed direct solid sampling method ETV-ICP OES is well suited for the fast determination of oxygen in coals, varying in rank from lignite to semianthracite, in a content range of about 100 ppm up to 27% using 1.5 mg sample weight. This direct analysis method represents an accurate, advantageous alternative to currently used methods for estimation of total oxygen contents in coals. PMID- 26372176 TI - Construction of a porous three dimensional rare earth metal-sulfur-ligand open framework. AB - A slow reaction between Nd(3+) and piperazine-1,4-dicarbodithiolate disodium (Na2(pipzdtc)) affords a three dimensional (3D) anionic [Nd(pipzdtc)2]n(n-) framework with a dia net. The encapsulated disordered guest molecules could be partially exchanged by Ni(2+) accompanied by the quenching of the typical NIR luminescence of Nd(3+) ions. PMID- 26372178 TI - Cold Exposure Partially Corrects Disturbances in Lipid Metabolism in a Male Mouse Model of Glucocorticoid Excess. AB - High glucocorticoid concentrations are accompanied by metabolic side effects such as high plasma triglyceride (TG) concentrations. Liver, brown adipose tissue (BAT) and white adipose tissue are important regulators of plasma TG. Exposure to 4 degrees C reduces plasma TG concentrations, and we therefore aimed to study the interaction between glucocorticoid excess and 24 hours of exposure to 4 degrees C on lipid metabolism. For this, mice were implanted with 50-mg corticosterone or control pellets and housed for 24 hours at 23 degrees C or 4 degrees C 1 week later, after which various aspects of TG metabolism in liver, BAT, and white adipose tissue were studied. Corticosterone treatment resulted in a 3.8-fold increase of plasma TG concentrations. Increased TG was normalized by cold exposure, an effect still present 24 hours after cold exposure. Corticosterone treatment increased hepatic TG content by 3.5-fold and provoked secretion of large, TG-rich very low density lipoprotein particles. Cold exposure reduced very low density lipoprotein-TG secretion by approximately 50%. Corticosterone strongly decreased BAT activity: BAT weight increased by 3.5-fold, whereas uncoupling protein 1 (Ucp1) mRNA expression and Ucp1 protein content of BAT were reduced by 75% and 60%, respectively. Cold exposure partially normalized these parameters of BAT activity. The uptake of TG by BAT was not affected by corticosterone treatment but was increased 4.5-fold upon cold exposure. In conclusion, cold exposure normalizes corticosterone-induced hypertriglyceridemia, at least partly via activating BAT. PMID- 26372177 TI - Prenatal Exposures of Male Rats to the Environmental Chemicals Bisphenol A and Di(2-Ethylhexyl) Phthalate Impact the Sexual Differentiation Process. AB - The increasing incidence of reproductive anomalies, described as testicular dysgenesis syndrome, is thought to be related to the exposure of the population to chemicals in the environment. Bisphenol A (BPA) and di(2-ethylhexyl)phthalate (DEHP), which have hormonal and antihormonal activity, have attracted public attention due to their presence in consumer products. The present study investigated the effects of BPA and DEHP on reproductive development. Timed pregnant female rats were exposed to BPA and DEHP by gavage from gestational days 12 to 21. Results showed that prenatal exposures to test chemicals exerted variable effects on steroidogenic factor 1 and GATA binding protein 4 protein expression and increased (P < .05) sex-determining region Y-box 9 and antimullerian hormone protein in the infantile rat testis compared with levels in the control unexposed animals. Pituitary LHbeta and FSHbeta subunit protein expression was increased (P < .05) in BPA- and DEHP-exposed prepubertal male rats but were decreased (P < .05) in adult animals relative to control. Exposure to both BPA and DEHP in utero inhibited (P < .05) global DNA hydroxymethylation in the adult testis in association with altered DNA methyltransferase protein expression. Together the present data suggest that altered developmental programming in the testes associated with chemical exposures are related to the disruption of sexual differentiation events and DNA methylation patterns. The chemical-induced effects impact the development of steroidogenic capacity in the adult testis. PMID- 26372180 TI - Identification of California Condor Estrogen Receptors 1 and 2 and Their Activation by Endocrine Disrupting Chemicals. AB - Recently, California condors (Gymnogyps californianus) have been reintroduced to coastal regions of California where they feed on marine mammal carcasses. There is evidence that coastal-dwelling condors experience reproductive issues, such as eggshell thinning, likely resulting from exposure to endocrine-disrupting chemicals (EDCs). To address this problem, we have identified and cloned condor estrogen receptors (ESRs) 1 and 2 and characterized their activation by EDCs present in the coastal habitats where condors reside. Dichlorodiphenyltrichloroethane (DDT) and its metabolites all activated ESR1 and ESR2, although their relative potency differed between the receptors. Bisphenol A, dieldrin, trans-nonachlor, and polychlorinated biphenyl 52 (PCB52) moderately activated both ESRs, whereas PCB138 and PCB153 stimulated little to no activation. Overall, EDC activation of condor ESR2, which is the first ESR2 cloned from a raptor species, was greater than that of ESR1. Significant activation of both condor ESRs by EDCs occurred at high concentrations (>=1MUM), which are within the range of plasma levels of certain EDCs (eg, dichlorodiphenyldichloroethylene [p'p-DDE]) in coastal-dwelling condors. Finally, phylogenetic analyses of ESRs of 41 avian species identified a single amino acid position in ESR2 under positive selection. Mutation of this amino acid affected receptor activation by EDCs, suggesting the identity of this amino acid may influence EDC sensitivity of avian species. Together, these findings broaden our understanding of EDC interactions with ESRs in avian species. For condors specifically, these data could be used to evaluate EDC exposure risk at future release sites to identify those least likely to compromise the continued recovery of this species. PMID- 26372179 TI - Differences in the Osteogenic Differentiation Capacity of Omental Adipose-Derived Stem Cells in Obese Patients With and Without Metabolic Syndrome. AB - Multiple studies have suggested that the reduced differentiation capacity of multipotent adipose tissue-derived mesenchymal stem cells (ASCs) in obese subjects could compromise their use in cell therapy. Our aim was to assess the osteogenic potential of omental ASCs and to examine the status of the isolated CD34(negative)-enriched fraction of omental-derived ASCs from subjects with different metabolic profiles. Omental ASCs from normal-weight subjects and subjects with or without metabolic syndrome were isolated, and the osteogenic potential of omental ASCs was evaluated. Additionally, osteogenic and clonogenic potential, proliferation rate, mRNA expression levels of proteins involved in redox balance, and fibrotic proteins were examined in the CD34(negative)-enriched fraction of omental-derived ASCs. Both the omental ASCs and the CD34(negative) enriched fraction of omental ASCs from subjects without metabolic syndrome have a greater osteogenic potential than those from subjects with metabolic syndrome. The alkaline phosphatase and osteonectin mRNA were negatively correlated with nicotinamide adenine dinucleotide phosphate oxidase-2 mRNA and the mRNA expression levels of the fibrotic proteins correlated positively with nicotinamide adenine dinucleotide phosphate oxidase-5 mRNA and the homeostasis model assessment. Although the population doubling time was significantly higher in subjects with a body mass index of 25 kg/m(2) or greater, only the CD34(negative)-enriched omental ASC fraction in the subjects with metabolic syndrome had a higher population doubling time than the normal-weight subjects. The osteogenic, clonogenic, fibrotic potential, and proliferation rate observed in vitro suggest that omental ASCs from subjects without metabolic syndrome are more suitable for therapeutic osteogenic applications than those from subjects with metabolic syndrome. PMID- 26372181 TI - Reduced Circulating GDF11 Is Unlikely Responsible for Age-Dependent Changes in Mouse Heart, Muscle, and Brain. AB - Recent high-profile studies report conflicting data on the age-related change in circulating growth/differentiation factor 11 (GDF11) and myostatin as well as the former's influence on muscle regeneration. Both ligands bind and activate ActRIIB receptors with similar affinities and should therefore have similar actions, yet these studies suggest that GDF11 activates muscle regeneration whereas myostatin is well known to inhibit it. They also suggest that circulating GDF11 levels, but not those of myostatin, decline with age. We performed a careful assessment of the ELISA used to quantify circulating myostatin in these studies and determined that assay reagents significantly cross react with each protein, each of which is highly homologous. Circulating myostatin levels decreased with age and estimates of GDF11 levels using myostatin null mice indicate that they were almost 500 times lower than those for myostatin. This suggests that circulating GDF11 has little physiological relevance as it could not outcompete myostatin for ActRIIB binding sites. Together, these results further suggest that the previously reported aging muscle, heart, and brain phenotypes attributed to reduced circulating GDF11 should be reconsidered. PMID- 26372183 TI - Nanoscale Color Sorting of Surface Plasmons in a Double-Nanogap Structure with Multipolar Plasmon Excitation. AB - We demonstrated a new plasmonic nanodevice that spatially sorts photons according to their colors on the nanoscale while maintaining their nanoconcentration. The properties of this nanoscale color sorting based on constructive and destructive interferences between different multipolar plasmon modes are controlled by tuning the incidence angle of the incoming photons. The added ability of color sorting and its manipulation could significantly influence the development of possible photonic applications, including nanoscale spectroscopy and sensing. PMID- 26372182 TI - Electroactive polymer-peptide conjugates for adhesive biointerfaces. AB - Electroactive polymer-peptide conjugates have been synthesized by combining poly(3,4-ethylenedioxythiophene), a polythiophene derivative with outstanding properties, and an Arg-Gly-Asp (RGD)-based peptide in which Gly has been replaced by an exotic amino acid bearing a 3,4-ethylenedioxythiophene ring in the side chain. The incorporation of the peptide at the ends of preformed PEDOT chains has been corroborated by both FTIR and X-ray photoelectron spectroscopy. Although the morphology and topology are not influenced by the incorporation of the peptide at the ends of PEDOT chains, this process largely affects other surface properties. Thus, the wettability of the conjugates is considerably higher than that of PEDOT, independently of the synthetic strategy, whereas the surface roughness only increases when the conjugate is obtained using a competing strategy (i.e. growth of the polymer chains against termination by end capping). The electrochemical activity of the conjugates has been found to be higher than that of PEDOT, evidencing the success of the polymer-peptide links designed by chemical similarity. Density functional theory calculations have been used not only to ascertain the conformational preferences of the peptide but also to interpret the electronic transitions detected by UV-vis spectroscopy. Electroactive surfaces prepared using the conjugates displayed the higher bioactivities in terms of cell adhesion, with the relative viabilities being dependent on the roughness, wettability and electrochemical activity of the conjugate. In addition to the influence of the peptide fragment in the initial cell attachment and subsequent cell spreading and survival, the results indicate that PEDOT promotes the exchange of ions at the conjugate-cell interface. PMID- 26372184 TI - Total elbow arthroplasty: Influence of implant positioning on functional outcomes. AB - BACKGROUND: Restoring the axis of rotation is often considered crucial to achieving good functional outcomes of total elbow arthroplasty. The objective of this work was to evaluate whether variations in implant positioning correlated with clinical outcomes. HYPOTHESIS: Clinical outcomes are dictated by the quality of implant positioning. MATERIAL AND METHODS: A retrospective review was conducted of data from 25 patients (26 elbows). Function was assessed using a pain score, the Disabilities of the Arm, Shoulder, and Hand (DASH) Score, and the Mayo Elbow Performance Score (MEPS). The patients also underwent a clinical evaluation for measurements of motion range and flexion/extension strength. Position of the humeral and ulnar implants was assessed by computed tomography with reconstruction using OsiriX software. Indices reflecting anterior offset, lateral offset, valgus, height, and rotation were computed by subtracting the ulnar value of each of these variables from the corresponding humeral value. These indices provided a quantitative assessment of whether position errors for the two components had additive effects or, on the contrary, counterbalanced each other. Elbows with prosthetic loosening or extensive epiphyseal destruction were excluded. RESULTS: Of the 26 elbows, 5 were excluded. In the remaining 21 elbows, the discrepancy between the humeral and ulnar lateral offsets was significantly associated with pain intensity (P <= 0.05) and the MEPS (P <= 0.05). Anterior position of the ulna relative to the humerus was associated with decreased extension strength (P <= 0.05) and worse results for all functional parameters (P <= 0.05). DISCUSSION: In the absence of loosening, positioning errors seem to adversely affect functional outcomes, probably by placing inappropriate stress on the soft tissues. LEVEL OF EVIDENCE: III. PMID- 26372185 TI - Minimally invasive posterior transforaminal lumbar interbody fusion: One-year postoperative morbidity, clinical and radiological results of a prospective multicenter study of 182 cases. AB - INTRODUCTION: Interbody fusion is the gold standard treatment for the management of numerous diseases of the spine. Minimally invasive techniques may be more beneficial than conventional techniques. The main goal of this study was to report the one-year postoperative results of a series of posterior lumbar interbody fusions by a minimally invasive technique in relation to improvement in functional outcome, interbody fusion and morbidity. MATERIALS AND METHODS: Between January 2012 and May 2013, 182 patients treated by minimally invasive posterior transforaminal lumbar interbody fusion (TLIF) were included in this prospective multicenter study. Clinical assessment was based on a comparison of the preoperative and one-year postoperative Oswestry (ODI), SF-12 and Quebec Scores and the Visual Analog Scale (VAS). Surgical and postoperative follow-up data were evaluated. Radiological assessment was based preoperative and one-year postoperative full spine teleradiographs. Interbody fusion at one-year was systematically evaluated by CT scan. RESULTS: One hundred and eighty-two patients were included, mean age 58.9 years old. Surgery lasted a mean 101 minutes, mean preoperative bleeding was 143 mL, and mean radiation exposure was 247.4 cGy/cm(2). The rate of postoperative complications was 7.7%. The ODI, the Quebec Score, the SF-12 and the VAS were all significantly improved at one-year (P<0.0001). The rate of fusion was 72.6% at the final follow-up. There was no significant difference in functional outcome between patients with and without fusion. DISCUSSION: The one-year postoperative radiological results and functional outcome of minimally invasive posterior lumbar fusion are satisfactory. The benefits of this minimally invasive approach are mainly found in the first 6 postoperative months. Successful radiological interbody fusion was not correlated to functional outcome at the final follow-up. PMID- 26372186 TI - Synergistic Antiproliferative Effects of a New Cucurbitacin B Derivative and Chemotherapy Drugs on Lung Cancer Cell Line A549. AB - Nonsmall cell lung cancer (NSCLC) represents an important cause of mortality worldwide due to its aggressiveness and growing resistance to currently available therapy. Cucurbitacins have emerged as novel potential anticancer agents showing strong antiproliferative effects and can be promising candidates for combined treatments with clinically used anticancer agents. This study investigates the synergistic antiproliferative effects of a new semisynthetic derivative of cucurbitacin B (DACE) with three chemotherapy drugs: cisplatin (CIS), irinotecan (IRI), and paclitaxel (PAC) on A549 cells. The most effective combinations were selected for studies of the mechanism of action. Using an in silico tool, DACE seems to act by a different mechanism of action when compared with that of different classes of drugs already used in clinical settings. DACE also showed potent synergic effects with drugs, and the most potent combinations induced G2/M cell cycle arrest by modulating survivin and p53 expression, disruption of F actin cytoskeleton, and cell death by apoptosis. These treatments completely inhibited the clonogenic potential and did not reduce the proliferation of nontumoral lung cells (MRC-5). DACE also showed relevant antimigratory and anti invasive effects, and combined treatments modulated cell migration signaling pathways evolved with metastasis progression. The effects of DACE associated with drugs was potentiated by the oxidant agent l-buthionine-sulfoximine (BSO), and attenuated by N-acetilcysteine (NAC), an antioxidant agent. The antiproliferative effects induced by combined treatments were attenuated by a pan-caspase inhibitor, indicating that the effects of these treatments are dependent on caspase activity. Our data highlight the therapeutic potential of DACE used in combination with known chemotherapy drugs and offer important insights for the development of more effective and selective therapies against lung cancer. PMID- 26372187 TI - Bypass surgery versus endovascular interventions in severe or critical limb ischemia. AB - OBJECTIVE: Critical limb ischemia is associated with a significant morbidity and mortality. We systematically reviewed the evidence to compare bypass surgery with endovascular revascularization in patients with critical limb ischemia. METHODS: We systematically searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, CINAHL, and Scopus through October 2014 for comparative studies (randomized and nonrandomized). Predefined outcomes of interest were mortality, major amputation, patency, and wound healing. We pooled odds ratios (ORs) of the outcomes of interest using the random-effects model. RESULTS: Nine studies that enrolled 3071 subjects were included. There was no significant difference in mortality (OR, 0.72; 95% confidence interval [CI], 0.44-1.16) or amputation (OR, 1.2; 95% CI, 0.87-1.65). Bypass surgery was associated with higher primary patency (OR, 2.50; 95% CI, 1.25-4.99) and assisted primary patency (OR, 3.39; 95% CI, 1.53-7.51). The quality of evidence was low for mortality and amputation outcomes and moderate for patency outcomes. CONCLUSIONS: Low quality of evidence due to imprecision and heterogeneity suggests that bypass surgery and endovascular approaches may have similar effect on mortality and major amputations. However, better primary and primary assisted patency can be expected with surgery. PMID- 26372188 TI - Targets to prevent prolonged length of stay after endovascular aortic repair. AB - OBJECTIVE: Endovascular aneurysm repair (EVAR) is a commonly performed vascular operation. Yet, postoperative length of stay (LOS) varies greatly, even within institutions. The present study reviewed the morbidity, mortality, and the financial effect of increased LOS to establish modifiable factors associated with prolonged hospital LOS, with the goal of improving quality. METHODS: The Society for Vascular Surgery Vascular Quality Initiative database was used to identify all patients undergoing primary, elective EVAR at a single institution between January 1, 2011, and May 28, 2014. Preoperative patient characteristics, intraoperative details, postoperative factors, long-term outcomes, and cost data were reviewed using an Institutional Review Board-approved prospectively collected database. Multivariate analysis was used to determine statistical difference between patients with LOS <=2 days and >2 days. RESULTS: Complete 30 day variable and cost data were available for 138 patients with an average follow up of 12 months; of these, 46 (33%) had a LOS >2 days. Variables determined to be statistically significant predictors of prolonged LOS included aneurysm diameter (P = .03), American Society of Anesthesiologists Physical Status Classification score (P < .001), thromboembolectomy (P = .01), and increased postoperative cardiac (P < .001) and renal (P = .01) complications. Specifically, modifiable risk factors that contributed to increased LOS included performance of a concomitant procedure (P < .001), increased volume of iodinated contrast (P = .05), increased volume of intraoperative crystalloid (P = .05), placement in an intensive care unit (P < .001), return to the operating room (P < .001), and the use of vasoactive medications (P < .001). Hospital charges ($102,000 +/- $41,000 vs $180,000 +/- $73,000; P = .01) and costs ($27,000 +/- $10,000 vs $45,000 +/- $19,000 P = .01) were significantly higher in patients with prolonged LOS; however, there was no difference in physician charges ($8000 +/- $5700 vs $12,000 +/- $12,000; P = .09). Increased LOS after EVAR was associated with an increase in mortality at 1 month (0% vs 4% P = .05) and 12 months (3% vs 13% P = .03). CONCLUSIONS: This study highlights several modifiable risk factors leading to increased LOS after EVAR, including performance of concomitant procedures, admission to the intensive care unit, and postoperative renal and cardiac complications. Further, increased LOS was associated with increased charges, costs, morbidity, and mortality after EVAR. This study highlights specific areas of focus for decreasing LOS after EVAR and, in turn, improving quality in vascular surgery. PMID- 26372189 TI - The in-hospital costs of treating high-risk patients with fenestrated and branched endografts. AB - OBJECTIVE: This study determined the 30-day morbidity and mortality and in hospital costs of elective fenestrated (fEVAR) and branched (bEVAR) endovascular aneurysm repairs at a single academic institution and determined factors that influence them. METHODS: All elective fEVAR or bEVAR patients treated between November 2007 and March 2014 in a Canadian academic hospital were included. Procedural details, 30-day morbidity and mortality rates, and cost of hospitalization were analyzed. Nonparametric bootstrap analysis was used to compare means between groups and calculate confidence intervals (CIs). RESULTS: There were 84 consecutive fEVAR (n = 61) and bEVAR (n = 23) procedures. The 30 day mortality was 3.3% for fEVAR and 4.3% for bEVAR. Mean hospital stay was 7.2 +/- 0.8 days for fEVAR and 12.6 +/- 2.2 days for bEVAR. The mean cost of the index hospitalization was $57,000 for fEVAR and $91,000 for bEVAR. Device-related costs accounted for 55% of the total costs. The occurrence of intraoperative or postoperative events were used to further divide each of the fEVAR and bEVAR groups into "complicated hospitalization" (fEVAR, n = 10; bEVAR, n = 13) and "uncomplicated hospitalization" (fEVAR, n = 51; bEVAR, n = 10) groups. Device related costs were not significantly different between the complicated and uncomplicated hospitalization groups (mean difference [95% CI] fEVAR: $3383 [ $3405 to $9809], P = .3; and bEVAR: $1930 [-$7892 to $11,288], P = .68). However, there were significant differences between the complicated and uncomplicated hospitalization groups in hospital length of stay (mean difference [95% CI] fEVAR: 8.1 [3.0-13.2] days, P = .001; and bEVAR: 10.8 [5.9-19.9] days, P = .002) and nondevice-related costs (mean difference [95% CI,] fEVAR: $25,843 [$11,689 $43,247], P = .001; and bEVAR; $20,326 [$9362-$36,615], P = .002). CONCLUSIONS: bEVAR and fEVAR are expensive interventions. Intraoperative adverse events and postoperative systemic complications dramatically increase costs and length of stay. Measures to minimize complications will reduce hospitalization costs and improve patient outcomes. PMID- 26372190 TI - Comparison of posterior and medial approaches for popliteal artery aneurysms. AB - BACKGROUND: Long-term results of the posterior approach (PA) for the treatment of popliteal artery aneurysms are lacking in the literature. We reviewed our experience during a 13-year period in patients with popliteal artery aneurysms, comparing those treated through a PA with those operated on through a standard medial approach (MA). METHODS: Clinical data of all patients treated between February 1998 and October 2011 were retrospectively reviewed and outcomes analyzed. The Kaplan-Meier method was used to estimate survival, and chi(2), Wilcoxon, and log-rank tests were used for analysis. RESULTS: A total of 77 aneurysms were treated in 65 patients (64 men). Mean age was 68 years (range, 48 96 years). Thirty-six aneurysms were asymptomatic (47%). Mean sac diameter was 2.8 +/- 1 cm. A PA was used in 43 PAAs (55%) and an MA in 34. The PA and MA patients differed significantly in age (median being older), smoking history (more frequent in PA), and renal insufficiency and cerebrovascular disease (higher for MA). In 42 cases the aneurysm was symptomatic (54.5%) for chronic limb ischemia, with intermittent claudication in 18 patients, acute ischemia in 17, blue toe syndrome in 3, compression on adjacent structures in 3, and rupture with severe acute pain in 1. All PA repairs consisted of aneurysmectomy with an interposition graft with end-to-end anastomoses; among MA repairs, 22 interposition grafts and 12 bypasses were performed. A polytetrafluoroethylene graft was used in 54 cases. Five patients had an early thrombosis (two PA and three MA). No perioperative deaths occurred. Two patients sustained a permanent (PA) and a temporary (MA) peroneal nerve lesion. There were no early amputations. The median in-hospital stay was longer for MA (10 days) than for PA (7 days; P = .02). Median follow-up was 58.8 months (range, 5 days-166 months). Nine patients died during follow-up of unrelated causes. The 5-year primary and secondary patency rates were 59.6% +/- 8.6% and 96.5% +/- 3.4%, respectively, for PA, and 65.1% +/- 11.1% and 79.4% +/- 9.7%, respectively, for MA (P = .53 for primary patency rate and P = .22 for secondary patency rate). Limb salvage was 100% at 5 years and 93.3% +/- 6.4% at 10 years for PA and 91.1% +/- 6.3% at both time points for MA (P = .28). CONCLUSIONS: PA and MA both achieved satisfactory results in primary and secondary patency rates, as well as limb salvage, during long-term follow-up. The differences between the two groups were small and not statistically significant. PA was burdened by similar postoperative nerve and wound complications compared with MA. The in-hospital stay after PA was significantly lower. PMID- 26372191 TI - Outcomes of total percutaneous endovascular aortic repair for thoracic, fenestrated, and branched endografts. AB - OBJECTIVE: Percutaneous endovascular aortic repair (PEVAR) has been increasingly used to treat infrarenal abdominal aortic aneurysms, but few studies have evaluated the results in complex aortic aneurysms. We reviewed the technical success and clinical outcomes of PEVAR using large-diameter sheaths for the treatment of complex aortic aneurysms with thoracic, fenestrated, and branched stent grafts. METHODS: The clinical data of patients who underwent total PEVAR for descending thoracic aneurysm, thoracoabdominal aortic aneurysm, pararenal, and aortoiliac aneurysms using thoracic, fenestrated, and branched stent grafts between 2009 and 2014 were reviewed. Repairs with fenestrated-branched stent grafts were performed using commercially available or investigational devices under a physician-sponsored investigational device protocols. Percutaneous closure was performed using ultrasound guidance and two Perclose devices (Abbott Vascular, Santa Clara Calif) per femoral puncture site. End points were technical success, access-related complications, morbidity, and mortality. RESULTS: There were 102 patients, 77 male and 25 female, with a mean age of 75 +/- 8 years. Aneurysm extent was pararenal in 48 patients (47%), thoracoabdominal aortic aneurysm in 27 (26%), descending thoracic aneurysm in 19 (19%), and aortoiliac in 8 (8%). Fenestrated or branched endografts, or both, were placed in 72 patients (71%). Total percutaneous closure was performed in 170 femoral arteries using >=20F-diameter sheaths in 163 (96%). Technical success was obtained in 161 femoral arteries (95%). There were no factors associated with technical failure. Access-related complications occurred in five patients (5%), including femoral artery thrombosis in three (3%), and retroperitoneal hematoma or pseudoaneurysm in one patient each (1%). There were no 30-day deaths. Freedom from access related complications was 97% +/- 1% at 30 days and 1 year. No access-related complications occurred >30 days. CONCLUSIONS: Total percutaneous technique can be safely performed with a high technical success rate and low rate of access complications in patients with thoracic and complex aortic disease requiring large-diameter sheaths. The rate of access-related complications (5%) is similar to that reported for PEVAR of infrarenal abdominal aortic aneurysms using smaller profile devices. PMID- 26372193 TI - Patients started on hemodialysis with tunneled dialysis catheter have similar survival after arteriovenous fistula and arteriovenous graft creation. AB - OBJECTIVE: Current guidelines suggest that arteriovenous fistula (AVF) is associated with survival advantage over arteriovenous graft (AVG). However, AVFs often require months to become functional, increasing tunneled dialysis catheter (TDC) use, which can erode the benefit of an AVF. We sought to compare survival in patients with end-stage renal disease after creation of an AVF or AVG in patients starting hemodialysis (HD) with a TDC and to identify patient populations that may benefit from preferential use of AVG over AVF. METHODS: Using U.S. Renal Data System databases, we identified incident HD patients in 2005 through 2008 and observed them through 2008. Initial access type and clinical variables including albumin levels were assessed using U.S. Renal Data System data collection forms. Attempts at AVF and AVG creation in patients who started HD through a TDC were identified by Current Procedural Terminology codes. We accounted for the effect of changes in access type by truncating follow-up when an additional AVF or AVG was performed. Survival curves were then constructed, and log-rank tests were used for pairwise survival comparisons, stratified by age. Multivariate analysis was performed with Cox proportional hazards regressions; variables were chosen using stepwise elimination. An interaction of access type and albumin level was detected, and Cox models using differing thresholds for albumin level were constructed. The primary outcome was survival. RESULTS: Among the 138,245 patients who started with a TDC and had complete records amenable for analysis, 22.8% underwent AVF creation (mean age +/ standard deviation, 68.9 +/- 12.5 years; 27.8% mortality at 1 year) and 7.6% underwent AVG placement (70.2 +/- 12.0 years; 28.2% mortality) within 3 months of HD initiation; 69.6% remained with a TDC (63.2 +/- 15.4 years; 33.8% mortality). In adjusted Cox proportional hazards regression, AVF creation is equivalent to AVG placement in terms of survival (hazard ratio [HR], 0.98; 95% confidence interval [CI], 0.93-1.02; P = .349). AVG placement is superior to continued TDC use (HR, 1.54; 95% CI, 1.48-1.61; P < .001). In patients older than 80 years with albumin levels >4.0 g/dL, AVF creation is associated with higher mortality hazard compared with AVG creation (HR, 1.22; 95% CI, 1.04-1.43; P = .013). CONCLUSIONS: For patients who start HD through a TDC, placement of an AVF and AVG is associated with similar mortality hazard. Further study is necessary to determine the ideal access for patients in whom the survival advantage of an AVF over an AVG is uncertain. PMID- 26372194 TI - Endovascular aortic aneurysm repair in patients with narrow aortas using bifurcated stent grafts is safe and effective. AB - OBJECTIVE: Narrowing of the distal aortic bifurcation can result in stent graft compression or arterial disruption during endovascular aortic aneurysm repair (EVAR). The aim of our study was to evaluate results of EVAR in patients with narrow distal aortic bifurcations. METHODS: We reviewed the clinical data of 1070 patients who underwent EVAR between 2000 and 2011. Digital computed tomography angiograms were analyzed using centerline of flow measurements to determine aortic diameters. Patients with a distal aortic bifurcation diameter <18 mm were included in the study. End points were technical success, aortic disruption with retroperitoneal hemorrhage, stent graft complications (endoleaks, migration, sac enlargement, stenosis), reintervention, and iliac limb patency. RESULTS: EVAR was used to treat 112 patients (84 men and 28 women; mean age, 75 years) with aortic bifurcation <18 mm, including 34 (30%) who had diameter of <14 mm. Mean outer and inner aortic bifurcation diameter was 16 +/- 3 and 14 +/- 2 mm, respectively. Bifurcated stent grafts were used in 106 patients (95%). Six patients (5%) had planned aortouniiliac converters with femoral crossover graft. The aortic bifurcation was dilated after placement of bifurcated stent grafts using kissing balloon angioplasty in 80 patients (75%). All bifurcated stent grafts were successfully implanted, with no conversions to open repair or aortouniiliac converters. There were two early deaths (1.8%), and 12 patients (11%) developed early complications. No aortic disruptions or retroperitoneal hematomas occurred in the group treated with bifurcated grafts. After a median follow-up of 35 months, 11 patients (11%) treated by bifurcated stent grafts required reintervention to treat endoleak (n = 6) or iliac limb stenosis/occlusion (n = 5). One patient (17%) treated by aortouniiliac converter developed critical stenosis of an aortouniiliac graft limb, which was successfully treated with balloon angioplasty 29 months after the initial surgery. At 1 and 5 years, freedom from reintervention was 91% +/- 3% and 84% +/- 4%, respectively, for bifurcated stent grafts and 100% and 83% +/- 10%, respectively, for aortouniiliac converters. Primary and secondary iliac limb patency was 98% +/- 3% and 100%, respectively, for bifurcated stent grafts and 83% +/- 10% and 100%, respectively, for aortouniiliac converters. CONCLUSIONS: EVAR with bifurcated stent grafts is safe and effective in patients with a narrow distal aortic diameter, even when the aortic bifurcation measures <14 mm. Adjunctive balloon dilatation did not result in any bleeding complications from aortic disruption, and limb patency was excellent. Aortouniiliac converters are rarely needed for this indication. PMID- 26372195 TI - Groin hernia repair, surgeon volume, and patient-reported outcome measures (PROMs). PMID- 26372192 TI - Biochemically engineered stromal cell-derived factor 1-alpha analog increases perfusion in the ischemic hind limb. AB - BACKGROUND: Despite promising therapeutic innovation over the last decade, peripheral arterial disease remains a prevalent morbidity, as many patients are still challenged with peripheral ischemia. We hypothesized that delivery of engineered stromal cell-derived factor 1-alpha (ESA) in an ischemic hind limb will yield significant improvement in perfusion. METHODS: Male rats underwent right femoral artery ligation, and animals were randomized to receive a 100 MUL injection of saline (n = 9) or 6 MUg/kg dosage of equal volume of ESA (n = 12) into the ipsilateral quadriceps muscle. Both groups of animals were also given an intraperitoneal injection of 40 MUg/kg of granulocyte macrophage colony stimulating factor (GMCSF). Perfusion was quantified using a laser Doppler imaging device preoperatively, and on postoperative days 0, 7, and 14. Immunohistochemistry was performed to quantify angiogenesis on day 14, and an mRNA profile was evaluated for angiogenic and inflammatory markers. RESULTS: Compared with the saline/GMCSF group at day 14, the ESA/GMCSF-injected animals had greater reperfusion ratios (Saline/GMCSF, 0.600 +/- 0.140 vs ESA/GMCSF, 0.900 +/- 0.181; group effect P = .006; time effect P < .0001; group*time effect P < .0001), elevated capillary density (10*; Saline/GMCSF, 6.40 +/- 2.01 vs ESA/GMCSF, 18.55 +/- 5.30; P < .01), and increased mRNA levels of vascular endothelial growth factor-A (Saline/GMCSF [n = 6], 0.298 +/- 0.205 vs ESA/GMCSF [n = 8], 0.456 +/- 0.139; P = .03). CONCLUSIONS: Delivery of ESA significantly improves perfusion in a rat model of peripheral arterial disease via improved neovasculogenesis, a finding which may prove beneficial in the treatment strategy for this debilitating disease. PMID- 26372196 TI - Inhibition of fatty acid synthase with C75 decreases organ injury after hemorrhagic shock. AB - BACKGROUND: Hemorrhagic shock is the primary cause of morbidity and mortality in the intensive care units in patients under the age of 35. Several organs, including the lungs, are seriously affected by hemorrhagic shock and inadequate resuscitation. Excess free fatty acids have shown to trigger inflammation in various disease conditions. C75 is a small compound that inhibits fatty acid synthase, a key enzyme in the control of fatty acid metabolism that also stimulates fatty acid oxidation. We hypothesized that C75 treatment would be protective against hemorrhagic shock. METHODS: Adult male Sprague-Dawley rats were cannulated with a femoral artery catheter and subjected to controlled bleeding. Blood was shed to maintain a mean arterial pressure of 30 mm Hg for 90 minutes, then resuscitated over 30 minutes with a crystalloid volume equal to twice the volume of shed blood. Fifteen minutes into the 30-minute resuscitation, the rats received either intravenous infusion of C75 (1 mg/kg body weight) or vehicle (20% dimethyl sulfoxide). Blood and tissue samples were collected 6 hours after resuscitation (ie, 7.5 hours after hemorrhage) for analysis. RESULTS: After hemorrhage and resuscitation, C75 treatment decreased the increase in serum free fatty acids by 48%, restored adenosine triphosphate levels, and stimulated carnitine palmitoyl transferase-1 activity. Administration of C75 decreased serum levels of markers of injury (aspartate aminotransferase, lactate, and lactate dehydrogenase) by 38%, 32%, and 78%, respectively. Serum creatinine and blood urea nitrogen were also decreased significantly by 38% and 40%, respectively. These changes correlated with decreases in neutrophil infiltration in the lung, evidenced by decreases in Gr-1-stained cells and myeloperoxidase activity and improved lung histology. Finally, administration of C75 decreased pulmonary mRNA levels of cyclooxygenase-2 and interleukin-6 by 87% and 65%, respectively. CONCLUSION: Administration of C75 after hemorrhage and resuscitation decreased the increase in serum free fatty acids, decreased markers of tissue injury, downregulated the expression of inflammatory mediators, and decreased neutrophil infiltration and lung injury. Thus, the dual action of inhibiting fatty acid synthesis and stimulating fatty acid oxidation by C75 could be developed as a promising adjuvant therapy strategy to protect against hemorrhagic shock. PMID- 26372197 TI - In response to: Letter to the Editor. PMID- 26372198 TI - Autoradiographic and histopathological studies of boric acid-mediated BNCT in hepatic VX2 tumor-bearing rabbits: Specific boron retention and damage in tumor and tumor vessels. AB - Hepatoma is a malignant tumor that responds poorly to conventional therapies. Boron neutron capture therapy (BNCT) may provide a better way for hepatoma therapy. In this research, (10)B-enriched boric acid (BA, 99% (10)B) was used as the boron drug. A multifocal hepatic VX2 tumor-bearing rabbit model was used to study the mechanisms of BA-mediated BNCT. Autoradiography demonstrated that BA was selectively targeted to tumors and tumor vessels. Histopathological examination revealed the radiation damage to tumor-bearing liver was concentrated in the tumor regions during BNCT treatment. The selective killing of tumor cells and the destruction of the blood vessels in tumor masses may be responsible for the success of BA-mediated BNCT for liver tumors. PMID- 26372199 TI - Hereditary Persistence of Fetal Hemoglobin Caused by Single Nucleotide Promoter Mutations in Sickle Cell Trait and Hb SC Disease. AB - Hereditary persistence of fetal hemoglobin (HPFH) can be caused by point mutations in the gamma-globin gene promoters. We report three rare cases: a child compound heterozygous for Hb S (HBB: c.20A > T) and HPFH with a novel point mutation in the (A)gamma-globin gene promoter who had 42.0% Hb S, 17.0% Hb A and 38.0% Hb F; a man with Hb SC (HBB: c.19G > A) disease and a point mutation in the (G)gamma-globin gene promoter who had 54.0% Hb S, 18.0% Hb C and 25.0% Hb F; a child heterozygous for Hb S and HPFH due to mutations in both the (A)gamma- and (G)gamma-globin gene promoters in cis [(G)gamma(A)gamma(beta(+)) HPFH], with 67.0% Hb A, 6.5% Hb S and 25.0% Hb F. PMID- 26372200 TI - Perceived addiction to Internet pornography and psychological distress: Examining relationships concurrently and over time. AB - In the United States, Internet pornography use is a common behavior that has risen in popularity in recent years. The present study sought to examine potential relationships between pornography use and well-being, with a particular focus on individual perceptions of pornography use and feelings of addiction. Using a large cross-sectional sample of adults (N = 713), perceived addiction to Internet pornography predicted psychological distress above and beyond pornography use itself and other relevant variables (e.g., socially desirable responding, neuroticism). This model was replicated using a large cross-sectional sample of undergraduates (N = 1,215). Furthermore, a 1-year, longitudinal follow up with a subset of this sample (N = 106) revealed a relationship between perceived addiction to Internet pornography and psychological distress over time, even when controlling for baseline psychological distress and pornography use. Collectively, these findings suggest that perceived addiction to Internet pornography, but not pornography use itself, is uniquely related to the experience of psychological distress. PMID- 26372201 TI - Transformative Two-Dimensional Array Configurations by Geometrical Shape-Shifting Protein Microstructures. AB - Two-dimensional (2D) geometrical shape-shifting is prevalent in nature, but remains challenging in man-made "smart" materials, which are typically limited to single-direction responses. Here, we fabricate geometrical shape-shifting bovine serum albumin (BSA) microstructures to achieve circle-to-polygon and polygon-to circle geometrical transformations. In addition, transformative two-dimensional microstructure arrays are demonstrated by the ensemble of these responsive microstructures to confer structure-to-function properties. The design strategy of our geometrical shape-shifting microstructures focuses on embedding precisely positioned rigid skeletal frames within responsive BSA matrices to direct their anisotropic swelling under pH stimulus. This is achieved using layer-by-layer two photon lithography, which is a direct laser writing technique capable of rendering spatial resolution in the sub-micrometer length scale. By controlling the shape, orientation and number of the embedded skeletal frames, we have demonstrated well-defined arc-to-corner and corner-to-arc transformations, which are essential for dynamic circle-to-polygon and polygon-to-circle shape-shifting, respectively. We further fabricate our shape-shifting microstructures in periodic arrays to experimentally demonstrate the first transformative 2D patterned arrays. Such versatile array configuration transformations give rise to structure to-physical properties, including array porosity and pore shape, which are crucial for the development of on-demand multifunctional "smart" materials, especially in the field of photonics and microfluidics. PMID- 26372202 TI - A Deep and Autoregressive Approach for Topic Modeling of Multimodal Data. AB - Topic modeling based on latent Dirichlet allocation (LDA) has been a framework of choice to deal with multimodal data, such as in image annotation tasks. Another popular approach to model the multimodal data is through deep neural networks, such as the deep Boltzmann machine (DBM). Recently, a new type of topic model called the Document Neural Autoregressive Distribution Estimator (DocNADE) was proposed and demonstrated state-of-the-art performance for text document modeling. In this work, we show how to successfully apply and extend this model to multimodal data, such as simultaneous image classification and annotation. First, we propose SupDocNADE, a supervised extension of DocNADE, that increases the discriminative power of the learned hidden topic features and show how to employ it to learn a joint representation from image visual words, annotation words and class label information. We test our model on the LabelMe and UIUC Sports data sets and show that it compares favorably to other topic models. Second, we propose a deep extension of our model and provide an efficient way of training the deep model. Experimental results show that our deep model outperforms its shallow version and reaches state-of-the-art performance on the Multimedia Information Retrieval (MIR) Flickr data set. PMID- 26372203 TI - Depth Estimation and Specular Removal for Glossy Surfaces Using Point and Line Consistency with Light-Field Cameras. AB - Light-field cameras have now become available in both consumer and industrial applications, and recent papers have demonstrated practical algorithms for depth recovery from a passive single-shot capture. However, current light-field depth estimation methods are designed for Lambertian objects and fail or degrade for glossy or specular surfaces. The standard Lambertian photoconsistency measure considers the variance of different views, effectively enforcing point consistency, i.e., that all views map to the same point in RGB space. This variance or point-consistency condition is a poor metric for glossy surfaces. In this paper, we present a novel theory of the relationship between light-field data and reflectance from the dichromatic model. We present a physically-based and practical method to estimate the light source color and separate specularity. We present a new photo consistency metric, line-consistency, which represents how viewpoint changes affect specular points. We then show how the new metric can be used in combination with the standard Lambertian variance or point-consistency measure to give us results that are robust against scenes with glossy surfaces. With our analysis, we can also robustly estimate multiple light source colors and remove the specular component from glossy objects. We show that our method outperforms current state-of-the-art specular removal and depth estimation algorithms in multiple real world scenarios using the consumer Lytro and Lytro Illum light field cameras. PMID- 26372204 TI - Coherency Sensitive Hashing. AB - Coherency Sensitive Hashing (CSH) extends Locality Sensitivity Hashing (LSH) and PatchMatch to quickly find matching patches between two images. LSH relies on hashing, which maps similar patches to the same bin, in order to find matching patches. PatchMatch, on the other hand, relies on the observation that images are coherent, to propagate good matches to their neighbors in the image plane, using random patch assignment to seed the initial matching. CSH relies on hashing to seed the initial patch matching and on image coherence to propagate good matches. In addition, hashing lets it propagate information between patches with similar appearance (i.e., map to the same bin). This way, information is propagated much faster because it can use similarity in appearance space or neighborhood in the image plane. As a result, CSH is at least three to four times faster than PatchMatch and more accurate, especially in textured regions, where reconstruction artifacts are most noticeable to the human eye. We verified CSH on a new, large scale, data set of 133 image pairs and experimented on several extensions, including: k nearest neighbor search, the addition of rotation and matching three dimensional patches in videos. PMID- 26372205 TI - A Clearer Picture of Total Variation Blind Deconvolution. AB - Blind deconvolution is the problem of recovering a sharp image and a blur kernel from a noisy blurry image. Recently, there has been a significant effort on understanding the basic mechanisms to solve blind deconvolution. While this effort resulted in the deployment of effective algorithms, the theoretical findings generated contrasting views on why these approaches worked. On the one hand, one could observe experimentally that alternating energy minimization algorithms converge to the desired solution. On the other hand, it has been shown that such alternating minimization algorithms should fail to converge and one should instead use a so-called Variational Bayes approach. To clarify this conundrum, recent work showed that a good image and blur prior is instead what makes a blind deconvolution algorithm work. Unfortunately, this analysis did not apply to algorithms based on total variation regularization. In this manuscript, we provide both analysis and experiments to get a clearer picture of blind deconvolution. Our analysis reveals the very reason why an algorithm based on total variation works. We also introduce an implementation of this algorithm and show that, in spite of its extreme simplicity, it is very robust and achieves a performance comparable to the top performing algorithms. PMID- 26372206 TI - Scale Space Graph Representation and Kernel Matching for Non Rigid and Textured 3D Shape Retrieval. AB - In this paper we introduce a novel framework for 3D object retrieval that relies on tree-based shape representations (TreeSha) derived from the analysis of the scale-space of the Auto Diffusion Function (ADF) and on specialized graph kernels designed for their comparison. By coupling maxima of the Auto Diffusion Function with the related basins of attraction, we can link the information at different scales encoding spatial relationships in a graph description that is isometry invariant and can easily incorporate texture and additional geometrical information as node and edge features. Using custom graph kernels it is then possible to estimate shape dissimilarities adapted to different specific tasks and on different categories of models, making the procedure a powerful and flexible tool for shape recognition and retrieval. Experimental results demonstrate that the method can provide retrieval scores similar or better than state-of-the-art on textured and non textured shape retrieval benchmarks and give interesting insights on effectiveness of different shape descriptors and graph kernels. PMID- 26372207 TI - Learning SVM in Krein Spaces. AB - This paper presents a theoretical foundation for an SVM solver in Krein spaces. Up to now, all methods are based either on the matrix correction, or on non convex minimization, or on feature-space embedding. Here we justify and evaluate a solution that uses the original (indefinite) similarity measure, in the original Krein space. This solution is the result of a stabilization procedure. We establish the correspondence between the stabilization problem (which has to be solved) and a classical SVM based on minimization (which is easy to solve). We provide simple equations to go from one to the other (in both directions). This link between stabilization and minimization problems is the key to obtain a solution in the original Krein space. Using KSVM, one can solve SVM with usually troublesome kernels (large negative eigenvalues or large numbers of negative eigenvalues). We show experiments showing that our algorithm KSVM outperforms all previously proposed approaches to deal with indefinite matrices in SVM-like kernel methods. PMID- 26372208 TI - Multi-Graph Matching via Affinity Optimization with Graduated Consistency Regularization. AB - This paper addresses the problem of matching common node correspondences among multiple graphs referring to an identical or related structure. This multi-graph matching problem involves two correlated components: i) the local pairwise matching affinity across pairs of graphs; ii) the global matching consistency that measures the uniqueness of the pairwise matchings by different composition orders. Previous studies typically either enforce the matching consistency constraints in the beginning of an iterative optimization, which may propagate matching error both over iterations and across graph pairs; or separate affinity optimization and consistency enforcement into two steps. This paper is motivated by the observation that matching consistency can serve as a regularizer in the affinity objective function especially when the function is biased due to noises or inappropriate modeling. We propose composition-based multi-graph matching methods to incorporate the two aspects by optimizing the affinity score, meanwhile gradually infusing the consistency. We also propose two mechanisms to elicit the common inliers against outliers. Compelling results on synthetic and real images show the competency of our algorithms. PMID- 26372209 TI - A Multi-Task Learning Framework for Head Pose Estimation under Target Motion. AB - Recently, head pose estimation (HPE) from low-resolution surveillance data has gained in importance. However, monocular and multi-view HPE approaches still work poorly under target motion, as facial appearance distorts owing to camera perspective and scale changes when a person moves around. To this end, we propose FEGA-MTL, a novel framework based on Multi-Task Learning (MTL) for classifying the head pose of a person who moves freely in an environment monitored by multiple, large field-of-view surveillance cameras. Upon partitioning the monitored scene into a dense uniform spatial grid, FEGA-MTL simultaneously clusters grid partitions into regions with similar facial appearance, while learning region-specific head pose classifiers. In the learning phase, guided by two graphs which a-priori model the similarity among (1) grid partitions based on camera geometry and (2) head pose classes, FEGA-MTL derives the optimal scene partitioning and associated pose classifiers. Upon determining the target's position using a person tracker at test time, the corresponding region-specific classifier is invoked for HPE. The FEGA-MTL framework naturally extends to a weakly supervised setting where the target's walking direction is employed as a proxy in lieu of head orientation. Experiments confirm that FEGA-MTL significantly outperforms competing single-task and multi-task learning methods in multi-view settings. PMID- 26372211 TI - Effects of Atorvastatin (80 mg) Therapy on Quantity of Epicardial Adipose Tissue in Patients Undergoing Pulmonary Vein Isolation for Atrial Fibrillation. AB - Epicardial adipose tissue (EAT) has been recognized as a sensitive marker of cardiometabolic risk. Recent evidence suggests efficacy of long-term statin therapy in reducing EAT in patients with coronary artery disease. Whether short term statin therapy is associated with changes in the volume of EAT is currently unknown. A cohort of patients with atrial fibrillation who underwent pulmonary vein isolation were randomized to receive either 80 mg/day of atorvastatin (n = 38, 32 men, age 56 +/- 11 years) or placebo (n = 41, 33 men, age 56 +/- 10 years) for a 3-month period. EAT volume was assessed by cardiac computed tomography at baseline and at follow-up. Patients randomized to statin treatment exhibited a modest but significant decrease in median EAT volume (baseline vs follow-up: 92.3 cm(3) [62.0 to 133.3] vs 86.9 cm(3) [64.1 to 124.8], p <0.05), whereas median EAT remained unchanged in the placebo group (81.9 cm(3) [55.5 to 110.9] vs 81.3 cm(3) [57.1 to 110.5], p = NS). Changes in median systemic inflammatory markers and lipid profile were also seen with statin treatment: C-reactive protein (2.4 mg/L [0.7 to 3.7] vs 1.1 mg/L [0.5 to 2.7], p <0.05), total cholesterol (186 mg/dL [162.5 to 201] vs 123 mg/dL [99 to 162.5], p <0.001), and low-density lipoprotein cholesterol (116 mg/dL [96.5 to 132.5] vs 56 [40.5 to 81] mg/dL, p <0.001) diminished, whereas median body mass index did not change (27.8 kg/m(2) [25 to 30] versus 27.6 kg/m(2) [25.7 to 30.5], p = NS). No variations occurred in the placebo group. In conclusion, short-term intensive statin therapy significantly reduced the volume of EAT in patients with atrial fibrillation. PMID- 26372210 TI - CDKN3 mRNA as a Biomarker for Survival and Therapeutic Target in Cervical Cancer. AB - The cyclin-dependent kinase inhibitor 3 (CDKN3) gene, involved in mitosis, is upregulated in cervical cancer (CC). We investigated CDKN3 mRNA as a survival biomarker and potential therapeutic target for CC. CDKN3 mRNA was measured in 134 CC and 25 controls by quantitative PCR. A 5-year survival study was conducted in 121 of these CC patients. Furthermore, CDKN3-specific siRNAs were used to investigate whether CDKN3 is involved in proliferation, migration, and invasion in CC-derived cell lines (SiHa, CaSki, HeLa). CDKN3 mRNA was on average 6.4-fold higher in tumors than in controls (p = 8 x 10-6, Mann-Whitney). A total of 68.2% of CC patients over expressing CDKN3 gene (fold change >= 17) died within two years of diagnosis, independent of the clinical stage and HPV type (Hazard Ratio = 5.0, 95% CI: 2.5-10, p = 3.3 x 10-6, Cox proportional-hazards regression). In contrast, only 19.2% of the patients with lower CDKN3 expression died in the same period. In vitro inactivation of CDKN3 decreased cell proliferation on average 67%, although it had no effect on cell migration and invasion. CDKN3 mRNA may be a good survival biomarker and potential therapeutic target in CC. PMID- 26372212 TI - Usefulness of Antibodies to Oxidized Low-Density Lipoproteins as Predictors of Morbidity and Prognosis in Heart Failure Patients Aged >=65 Years. AB - Elevated level of antibodies to oxidized low-density lipoproteins (OxLDL-Ab) was shown to reliably predict morbidity and mortality in patients with heart failure (HF). Two hundred and eleven patients aged >=65 years treated at the Heart Failure Unit, Tel Aviv-Sourasky Medical Center, were included in this retrospective study. The end points were time to the first hospitalization (morbidity), all-cause mortality, and a combination of the two (composite outcome). HF duration ranged from 8 to 10.5 years. Mean follow-up was 5.2 +/- 1.9 years. The mean number of clinical visits was 18.3 +/- 2.4. Participants were divided according to OxLDL-Ab level. Group 1 had Ox LDL-Ab level <200 arbitrary U/ml. Group 2 had OxLDL-Ab level >=200 arbitrary U/ml. The mean time to the first hospitalization was 25.8 +/- 17.0 months. The mortality rate was 44.1%. Combined mortality and hospitalization rate was 58.8%. Adjusted hazard ratios of OxLDL-Ab for hospitalization were 3.16, p <0.001, 95% confidence interval 1.740 to 5.736 and for composite outcome 2.67, p <0.001, 95% confidence interval 1.580 to 4.518. In conclusion, OxLDL-Ab level was the best predictor for both hospitalization and composite outcome. It may, thus, serve as a useful clue for early and more accurate detection of poorly controlled HF and as a marker for imminent exacerbations of thereof. PMID- 26372213 TI - Quantitative Evaluation of Mitral Regurgitation Secondary to Mitral Valve Prolapse by Magnetic Resonance Imaging and Echocardiography. AB - The present prospective study was designed to evaluate the accuracy of quantitative assessment of mitral regurgitant fraction (MRF) by echocardiography and cardiac magnetic resonance imaging (cMRI) in the modern era using as reference method the blinded multiparametric integrative assessment of mitral regurgitation (MR) severity. 2-Dimensional (2D) and 3-dimensional (3D) MRF by echocardiography (2D echo MRF and 3D echo MRF) were obtained by measuring the difference in left ventricular (LV) total stroke volume (obtained from either 2D or 3D acquisition) and aortic forward stroke volume normalized to LV total stroke volume. MRF was calculated by cMRI using either (1) (LV stroke volume - systolic aortic outflow volume by phase contrast)/LV stroke volume (cMRI MRF [volumetric]) or (2) (mitral inflow volume - systolic aortic outflow volume)/mitral inflow volume (cMRI MRF [phase contrast]). Six patients had 1 + MR, 6 patients had 2 + MR, 12 patients had 3 + MR, and 10 had 4 + MR. A significant correlation was observed between MR grading and 2D echo MRF (r = 0.60, p <0.0001) and 3D echo MRF (r = 0.79, p <0.0001), cMRI MRF (volumetric) (r = 0.87, p <0.0001), and cMRI MRF (phase contrast r = 0.72, p <0.001). The accuracy of MRF for the diagnosis of MR >=3+ or 4+ was the highest with cMRI MRF (volumetric) (area under the receiver operating characteristic curve [AUC] = 0.98), followed by 3D echo MRF (AUC = 0.96), 2D echo MRF (AUC = 0.90), and cMRI MRF (phase contrast; AUC = 0.83). In conclusion, MRF by cMRI (volumetric method) and 3D echo MRF had the highest diagnostic value to detect significant MR, whereas the diagnostic value of 2D echo MRF and cMRI MRF (phase contrast) was lower. Hence, the present study suggests that both cMRI (volumetric method) and 3D echo represent best approaches for calculating MRF. PMID- 26372214 TI - A possible critical point for nematic order on the basis of Landau free energy having dual instabilities for nano-segregated smectic liquid crystals. AB - Landau expansion of free energy assuming dual instabilities for the nano segregated SmA phase is analyzed. In addition to known phase sequences (on cooling, disordered isotropic liquid -> nematic phase -> smectic phase, and disordered isotropic liquid -> smectic phase), a new sequence (disordered isotropic liquid -> density wave with subsidiary nematic order -> smectic phase) and the existence of a critical point are demonstrated in the case where the instability for density wave formation occurs at a higher temperature. PMID- 26372215 TI - [Scimitar syndrome. Correlation anatomo-embryological]. AB - OBJECTIVES: To describe morphologically a toracoabdominal visceral block of a scimitar's syndrome case. We propose a pathogenetic theory wich explains the development of the pulmonary venous connection in this syndrome. METHOD: The anatomic specimen was described with the segmental sequential system. The situs was solitus, the connections between the cardiac segments and the associated anomalies were determined. The anatomy of both lungs, including the venous pulmonary connection, was described. A pathogenetic hypothesis was made, which explains the pulmonary venous connection throw a correlation between the pathology of this syndrome and the normal development of the pulmonary veins. RESULTS: The situs was solitus, the connections of the cardiac chambers were normal; there were hypoplasia and dysplasia of the right lung with sequestration of the inferior lobe; the right pulmonary veins were connected with a curved collector which drainaged into the suprahepatic segment of the inferior vena cava; the left pulmonary veins were open into the left atrium. The sequestered inferior lobe of the right lung received irrigation throw a collateral aortopulmonary vessel. There was an atrial septal defect. CONCLUSIONS: The pathogenetic hypothesis propose that the pulmonary venous connection in this syndrome represent the persistent of the Streeter's horizon xiv (28-30 days of development), period in which the sinus of the pulmonary veins has double connection, with the left atrium and with a primitive collector into the right viteline vein which forms the suprahepatic segment of the inferior vena cava. PMID- 26372216 TI - Levels and subtypes of depression should not be overlooked in research on neuroticism and cortisol. PMID- 26372217 TI - Further Evidence of an Association between the Presence of Leishmania RNA Virus 1 and the Mucosal Manifestations in Tegumentary Leishmaniasis Patients. AB - Tegumentary Leishmaniasis (TL) is endemic in Latin America, and Brazil contributes approximately 20 thousand cases per year. The pathogenesis of TL, however, is still not fully understood. Clinical manifestations vary from cutaneous leishmaniasis (CL) to more severe outcomes, such as disseminated leishmaniasis (DL), mucosal leishmaniasis (ML) and diffuse cutaneous leishmaniasis (DCL). Many factors have been associated with the severity of the disease and the development of lesions. Recent studies have reported that the presence of Leishmania RNA virus 1 infecting Leishmania (Leishmania RNA virus 1, LRV1) is an important factor associated with the severity of ML in experimental animal models. In the present study, 156 patients who attended Rondonia's Hospital of Tropical Medicine with both leishmaniasis clinical diagnoses (109 CL; 38 ML; 5 CL+ML; 3 DL and 1 DCL) and molecular diagnoses were investigated. The clinical diagnosis were confirmed by PCR by targeting hsp70 and kDNA DNA sequences and the species causing the infection were determined by HSP70 PCR RFPL. The presence of LVR1 was tested by RT-PCR. Five Leishmania species were detected: 121 (77.6%) samples were positive for Leishmania (Viannia) braziliensis, 18 (11.5%) were positive for Leishmania (V.) guyanensis, 3 (1.8%) for Leishmania (V.) lainsoni, 2 (1.3%) for Leishmania (Leishmania) amazonensis and 2 (1.3%) for Leishmania (V.) shawi. Six (3.9%) samples were positive for Leishmania sp. but the species could not be determined, and 4 (2.6%) samples were suggestive of mixed infection by L. (V.) braziliensis and L. (V.) guyanensis. The virus was detected in L. braziliensis (N = 54), L. guyanensis (N = 5), L. amazonensis (N = 2), L. lainsoni (N = 1) and inconclusive samples (N = 6). Patients presenting with CL+ML, DL and DCL were excluded from further analysis. Association between the presence of the virus and the disease outcome were tested among the remaining 147 patients (CL = 109 and ML = 38). Of them, 71.1% (n = 27) mucosal lesions were positive for LRV1, and 28.9% (n = 11) were negative. In cutaneous lesions, 36.7% (n = 40) were positive and 63.3% (n = 69) were negative for LRV1. The ratio P(ML|LRV1+)/P(ML|LRV1-) was 2.93 (CI95% 1.57...5.46; p<0.001), thus corroborating the hypothesis of the association between LRV1 and the occurrence of mucosal leishmaniasis, as previously described in animal models; it also indicates that LRV1 is not the only factor contributing to the disease outcome. PMID- 26372218 TI - Smoking, Suicidality and Psychosis: A Systematic Meta-Analysis. AB - The aim of this study is to systematically review the literature that explored the association between smoking and suicidal risk among those with serious mental illness and to estimate the risk of suicidal behaviors attributable to smoking among this patient group. Multiple databases (CINAHL, PsycINFO, EMBASE, Informit Health Collection and the Cochrane Library databases) were searched from 1 January 1975 through 15 January 2014, along with references from relevant articles for observational studies that ascertained the association between smoking and suicidal behaviors among patients with psychotic disorders conducted in adult patients. Thirteen studies involving 6813 patients with severe mental illness were included. We found that smoking was significantly associated with suicidality in psychosis with an Odds Ratio of 2.12 (95% CI 1.67-2.7). Smoking is associated with suicidal risk amongst individuals with a severe mental illness; however, it is still unclear whether this represents a true risk factor or a confounder or a mediator via mechanisms, hitherto unknown, needs to be studied further. PMID- 26372219 TI - Early real-time estimation of the basic reproduction number of emerging or reemerging infectious diseases in a community with heterogeneous contact pattern: Using data from Hong Kong 2009 H1N1 Pandemic Influenza as an illustrative example. AB - Emerging and re-emerging infections such as SARS (2003) and pandemic H1N1 (2009) have caused concern for public health researchers and policy makers due to the increased burden of these diseases on health care systems. This concern has prompted the use of mathematical models to evaluate strategies to control disease spread, making these models invaluable tools to identify optimal intervention strategies. A particularly important quantity in infectious disease epidemiology is the basic reproduction number, R0. Estimation of this quantity is crucial for effective control responses in the early phase of an epidemic. In our previous study, an approach for estimating the basic reproduction number in real time was developed. This approach uses case notification data and the structure of potential transmission contacts to accurately estimate R0 from the limited amount of information available at the early stage of an outbreak. Based on this approach, we extend the existing methodology; the most recent method features intra- and inter-age groups contact heterogeneity. Given the number of newly reported cases at the early stage of the outbreak, with parsimony assumptions on removal distribution and infectivity profile of the diseases, experiments to estimate real time R0 under different levels of intra- and inter-group contact heterogeneity using two age groups are presented. We show that the new method converges more quickly to the actual value of R0 than the previous one, in particular when there is high-level intra-group and inter-group contact heterogeneity. With the age specific contact patterns, number of newly reported cases, removal distribution, and information about the natural history of the 2009 pandemic influenza in Hong Kong, we also use the extended model to estimate R0 and age-specific R0. PMID- 26372221 TI - Diagnostic strategy for the assessment of axillary lymph node status in breast cancer. AB - The nodal status in breast cancer is a major prognostic factor in terms of survival. It also plays a role in the therapeutic decision-making process. Therefore, the evaluation of lymph node involvement in breast cancer is imperative in establishing a personalized treatment scheme. The sentinel lymph node procedure has proved successful for small breast tumors (T1-T2), limiting axillary lymphadenectomy and its side effects without changing overall survival. Even so, a substantial number of women must undergo axillary lymphadenectomy during a second surgery when the analysis of the sentinel node discloses major nodal involvement. Imaging can improve patient selection, especially those who appear eligible for immediate axillary lymphadenectomy. Ultrasound is able to depict morphological abnormalities in the lymph nodes such as cortical thickening, peripheral vascularization, hilar infiltration and loss of the kidney shaped appearance of a normal node. When ultrasound is negative, the risk of massive nodal involvement is limited, thus allowing the oncologist to take an approach with the sentinel lymph node procedure. Magnetic resonance imaging (MRI) can also be useful in detecting pathological lymph nodes, particularly with diffusion-weighted MRI sequence. PMID- 26372220 TI - Combined Small RNA and Degradome Sequencing Reveals Novel MiRNAs and Their Targets in the High-Yield Mutant Wheat Strain Yunong 3114. AB - Wheat is one of the main food sources worldwide; large amount studies have been conducted to improve wheat production. MicroRNAs (miRNAs) with about 20-30 nucleotide are a class of regulatory small RNAs (sRNAs), which could regulate gene expression through sequence-specific base pairing with target mRNAs, playing important roles in plant growth. An ideal plant architecture (IPA) is crucial to enhance yield in bread wheat. In this study, the high-yield wheat strain Yunong 3114 was EMS-mutagenesis from the wild-type strain Yunong 201, exhibiting a preferable plant structure compared with the wild-type strain. We constructed small RNA and degradome libraries from Yunong 201 and Yunong 3114, and performed small RNA sequencing of these libraries in order identify miRNAs and their targets related to IPA in wheat. Totally, we identified 488 known and 837 novel miRNAs from Yunong 3114 and 391 known and 533 novel miRNAs from Yunong 201. The number of miRNAs in the mutant increased. A total of 37 known and 432 putative novel miRNAs were specifically expressed in the mutant strain; furthermore, 23 known and 159 putative novel miRNAs were specifically expressed in the wild-type strain. A total of 150 known and 100 novel miRNAs were differentially expressed between mutant and wild-type strains. Among these differentially expressed novel miRNAs, 4 and 8 predict novel miRNAs were evidenced by degradome sequencing and showed up-regulated and down-regulated expressions in the mutant strain Yunong 3114, respectively. Targeted gene annotation and previous results indicated that this set of miRNAs is related to plant structure. Our results further suggested that miRNAs may be necessary to obtain an optimal wheat structure. PMID- 26372222 TI - Inflammatory breast disease: The radiologist's role. AB - Mastitis is the inflammation of breast tissue. From a pathophysiological point of view, mastitis reflects a variety of underlying etiologies. It can be due to non infectious inflammation, infection (generally of bacterial origin) but can also be caused by inflammation resulting from malignant tumor growth. Mastitis always manifests clinically by three cardinal signs of inflammation, which are redness, heat and pain. Breast specialists examining women with mastitis should proceed as follows: first, it is important to distinguish between cancer-related and non cancer-related breast inflammation, since their clinical presentation can be misleading. Cancer-related mastitis reflecting the presence of aggressive cancer is less commonly observed than other forms of mastitis but its diagnosis, which can sometimes be difficult, needs to be made, or excluded, without delay. Once cancer-related mastitis has been excluded, the causes of inflammation should be elucidated to enable rapid treatment and patient recovery. PMID- 26372223 TI - Microbial Community Dynamics and Activity Link to Indigo Production from Indole in Bioaugmented Activated Sludge Systems. AB - Biosynthesis of the popular dyestuff indigo from indole has been comprehensively studied using pure cultures, but less has been done to characterize the indigo production by microbial communities. In our previous studies, a wild strain Comamonas sp. MQ was isolated from activated sludge and the recombinant Escherichia coli nagAc carrying the naphthalene dioxygenase gene (nag) from strain MQ was constructed, both of which were capable of producing indigo from indole. Herein, three activated sludge systems, G1 (non-augmented control), G2 (augmented with Comamonas sp. MQ), and G3 (augmented with recombinant E. coli nagAc), were constructed to investigate indigo production. After 132-day operation, G3 produced the highest yields of indigo (99.5 +/- 3.0 mg/l), followed by G2 (27.3 +/- 1.3 mg/l) and G1 (19.2 +/- 1.2 mg/l). The microbial community dynamics and activities associated with indigo production were analyzed by Illumina Miseq sequencing of 16S rRNA gene amplicons. The inoculated strain MQ survived for at least 30 days, whereas E. coli nagAc was undetectable shortly after inoculation. Quantitative real-time PCR analysis suggested the abundance of naphthalene dioxygenase gene (nagAc) from both inoculated strains was strongly correlated with indigo yields in early stages (0-30 days) (P < 0.001) but not in later stages (30-132 days) (P > 0.10) of operation. Based on detrended correspondence analysis (DCA) and dissimilarity test results, the communities underwent a noticeable shift during the operation. Among the four major genera (> 1% on average), the commonly reported indigo-producing populations Comamonas and Pseudomonas showed no positive relationship with indigo yields (P > 0.05) based on Pearson correlation test, while Alcaligenes and Aquamicrobium, rarely reported for indigo production, were positively correlated with indigo yields (P < 0.05). This study should provide new insights into our understanding of indigo bio production by microbial communities. PMID- 26372224 TI - Catastrophic Regime Shift in Water Reservoirs and Sao Paulo Water Supply Crisis. AB - The relation between rainfall and water accumulated in reservoirs comprises nonlinear feedbacks. Here we show that they may generate alternative equilibrium regimes, one of high water-volume, the other of low water-volume. Reservoirs can be seen as socio-environmental systems at risk of regime shifts, characteristic of tipping point transitions. We analyze data from stored water, rainfall, and water inflow and outflow in the main reservoir serving the metropolitan area of Sao Paulo, Brazil, by means of indicators of critical regime shifts, and find a strong signal of a transition. We furthermore build a mathematical model that gives a mechanistic view of the dynamics and demonstrates that alternative stable states are an expected property of water reservoirs. We also build a stochastic version of this model that fits well to the data. These results highlight the broader aspect that reservoir management must account for their intrinsic bistability, and should benefit from dynamical systems theory. Our case study illustrates the catastrophic consequences of failing to do so. PMID- 26372225 TI - XBP1-Independent UPR Pathways Suppress C/EBP-beta Mediated Chondrocyte Differentiation in ER-Stress Related Skeletal Disease. AB - Schmid metaphyseal chondrodysplasia (MCDS) involves dwarfism and growth plate cartilage hypertrophic zone expansion resulting from dominant mutations in the hypertrophic zone collagen, Col10a1. Mouse models phenocopying MCDS through the expression of an exogenous misfolding protein in the endoplasmic reticulum (ER) in hypertrophic chondrocytes have demonstrated the central importance of ER stress in the pathology of MCDS. The resultant unfolded protein response (UPR) in affected chondrocytes involved activation of canonical ER stress sensors, IRE1, ATF6, and PERK with the downstream effect of disrupted chondrocyte differentiation. Here, we investigated the role of the highly conserved IRE1/XBP1 pathway in the pathology of MCDS. Mice with a MCDS collagen X p.N617K knock-in mutation (ColXN617K) were crossed with mice in which Xbp1 was inactivated specifically in cartilage (Xbp1CartDeltaEx2), generating the compound mutant, C/X. The severity of dwarfism and hypertrophic zone expansion in C/X did not differ significantly from ColXN617K, revealing surprising redundancy for the IRE1/XBP1 UPR pathway in the pathology of MCDS. Transcriptomic analyses of hypertrophic zone cartilage identified differentially expressed gene cohorts in MCDS that are pathologically relevant (XBP1-independent) or pathologically redundant (XBP1-dependent). XBP1-independent gene expression changes included large-scale transcriptional attenuation of genes encoding secreted proteins and disrupted differentiation from proliferative to hypertrophic chondrocytes. Moreover, these changes were consistent with disruption of C/EBP-beta, a master regulator of chondrocyte differentiation, by CHOP, a transcription factor downstream of PERK that inhibits C/EBP proteins, and down-regulation of C/EBP beta transcriptional co-factors, GADD45-beta and RUNX2. Thus we propose that the pathology of MCDS is underpinned by XBP1 independent UPR-induced dysregulation of C/EBP-beta-mediated chondrocyte differentiation. Our data suggest that modulation of C/EBP-beta activity in MCDS chondrocytes may offer therapeutic opportunities. PMID- 26372226 TI - Profiling patterns of fecal 20-oxopregnane concentrations during ovarian cycles in free-ranging southern white rhinoceros (Ceratotherium simum simum). AB - Unlike their wild counterparts, many white rhinoceros females in captivity fail to reproduce successfully such that current captive populations are not self sustaining. The causes of the problem are poorly understood. Variation in cycle length and long periods of acyclicity are characteristics of the majority of these non-reproducing females in captivity but it is unknown whether these characteristics are a feature of reproductively successful free-ranging females. This study therefore aimed to monitor cyclic activity in a wild population of southern white rhinoceros at Lapalala Wilderness, South Africa, by measuring the concentrations of immunoreactive fecal progestagen metabolites (fPM). Five adult females were tracked twice per week for 20 months and if located a fresh fecal sample was collected. Reproductive events and group structural dynamics were also recorded and subsequently correlated with the fPM data. The baseline concentration of fPM was 0.69+/-0.20MUg/g DW while concentrations during pregnancy were 30-400-fold higher. The females exhibited estrous cycle lengths of 30.6+/-7.7 days and, based on fPM data, gestation length in one female was 502+/ 3 days. Year-round monitoring showed no clear evidence of seasonality in ovarian activity. During cyclic luteal activity females were often seen in the presence of a dominant bull. One female stopped cycling after removal of the local dominant bull and luteal activity only returned after a new bull was introduced. This suggests that white rhinoceros females in the wild might need external stimuli from a male to ovulate. These findings indicate that the irregular cyclicity reported for white rhinoceros housed in zoos and animal parks may result from conditions in captivity and account for reduced fertility. PMID- 26372228 TI - Estimation of Myocardial Strain and Contraction Phase From Cine MRI Using Variational Data Assimilation. AB - This paper presents a new method to estimate left ventricle deformations using variational data assimilation that combines image observations from cine MRI and a dynamic evolution model of the heart. The main contribution of the model is that it embeds parameters modeling the contraction / relaxation process. It estimates myocardial motion and contraction parameters simultaneously, providing accurate complementary information for diagnosis. The method was applied to synthetic datasets with known ground truth motion and to 47 patients MRI datasets acquired at three slice locations (base, mid-ventricle and apex). Radial and circumferential strain components were compared to those obtained with a reference tag tracking software, exhibiting good agreement with intraclass correlation coefficients (ICC) above 0.8. Results were also evaluated against wall motion score indices used to assess cardiac kinetics in clinical practice. The assimilation process overcame issues caused by temporal artifacts as a result of the dynamic model, compared to using the observation term alone. Moreover we found that the new dynamic model, consisting of a piecewise transport model acting independently on systole and diastole performed better than the standard continuous transport model, which oversmooths temporal variations. Estimated strain and contraction parameters significantly correlated to clinical scores, making them promising features for diagnosing not only hypokinesia but also dyskinesia. PMID- 26372227 TI - Interaction of meropenem with 'N' and 'B' isoforms of human serum albumin: a spectroscopic and molecular docking study. AB - Carbapenems are used to control the outbreak of beta-lactamases expressing bacteria. The effectiveness of drugs is influenced by its interaction with human serum albumin (HSA). Strong binding of carbapenems to HSA may lead to decreased bioavailability of the drug. The non-optimal drug dosage will provide a positive selection pressure on bacteria to develop resistance. Here, we investigated the interaction between meropenem and HSA at physiological pH 7.5 (N-isoform HSA) and non-physiological pH 9.2 (B-isoform HSA). Results showed that meropenem quenches the fluorescence of both 'N' and 'B' isoforms of HSA (DeltaG < 0 and binding constant ~10(4) M(-1)). Electrostatic interactions and van der Waal interactions along with H-bonds stabilized the complex of meropenem with 'N' and 'B' isoforms of HSA, respectively. Molecular docking results revealed that meropenem binds to HSA near Sudlow's site II (subdomain IIIA) close to Trp-214 with a contribution of a few residues of subdomain IIA. CD spectroscopy showed a change in the conformation of both the isoforms of HSA upon meropenem binding. The catalytic efficiency of HSA (only N-isoform) on p-nitrophenyl acetate was increased primarily due to a decrease in Km and an increase in kcat values. This study provides an insight into the molecular basis of interaction between meropenem and HSA. PMID- 26372229 TI - Double-barrelled resuscitation: A feasibility and simulation study of dual intraosseous needles into a single humerus. AB - INTRODUCTION: Resuscitation can be delayed, or impaired, by insufficient vascular access. This study examines whether dual-intraosseous needles, inserted into a single porcine humerus, can facilitate rapid and concomitant fluid and medication delivery. METHODS: After inserting one- and then two-intraosseous needles into the same porcine humerus, we determined the rate of fluid administration using (i) an infusion pump set to 999mL/h, and (ii) a standard pressure-bag set to 300mmHg. Next, we concomitantly infused blood, crystalloid and medications into the same medullary canal, using the two-needle set-up. Humeri were inspected for fluid-leakage, needle-displacement, and bone damage. RESULTS: Using an infusion pump, the mean normal-saline infusion-rate was significantly higher with dual intraosseous needles compared to a single-intraosseous needle: the infusion-rate was 16mL/min using dual-needles versus 8mL/min for a single needle set-up (p<0.001). In contrast, using the pneumatic pressure-bag, the infusion rate was not statistically different when comparing dual-intraosseous needles versus single-intraosseous: the infusion-rate was 22mL/min versus 21ml/min (p=0.4) for 500mL, and 22ml/min versus 21ml/min (p=0.64) for one-litre, respectively. Blood product could be infused at a mean rate of 20mL/min through one needle while tranexamic acid was simultaneously infused through a second. There were no complications with a dual-intraosseous set-up (no fluid leakage; no needle displacement; no high-pressure alarms, and no external bone-fractures or internal macrohistological damage) during any of our simulated resuscitation scenarios. CONCLUSIONS: This is the first published study evaluating dual-intraosseous needles in a single bone. Despite limitations, this preliminary study (using a porcine humerus) suggests that dual-intraosseous needles are feasible. For critically-ill patients with limited insertion sites, dual-intraosseous (a.k.a. 'double-barrelled resuscitation') may facilitate rapid and concurrent resuscitation. PMID- 26372231 TI - Verifying NG tube placement in children. PMID- 26372230 TI - Course of recovery for whiplash associated disorders in a compensation setting. AB - CONTEXT: The detailed course of recovery following compensable whiplash associated disorders (WAD) is not well understood. Some people recover within months and others report symptoms for extended periods. Recent research identified distinct recovery pathways. Identifying recovery pathways for people with this condition in compensable settings could assist clinical and claim management. STUDY OBJECTIVE: This study aimed to identify recovery trajectories based on disability, pain catastrophising and mental health and, secondly, to examine developmental linkages between the trajectories. STUDY DESIGN: A cohort of 246 people with compensable WAD were followed for 24 months after a motor vehicle related injury. OUTCOME MEASURES: Functional Rating Index (FRI), Pain Catastrophising Scale (PCS) and the SF36 Mental Component Score (SF 36 MCS). METHOD: Group-based trajectory analytical techniques were used to identify distinct post-injury profiles. Multinominal logistic regression modelling identified factors associated with membership of different trajectories. RESULTS: 246 people were enrolled a median of 72 days after injury. Three trajectories were identified for the measures used and their prevalences, respectively, were: for disability (FRI) they were mild (47%), moderate (31%), and severe (22%); for pain catastrophising (PCS) they were non-catastrophisers (55%), moderate-low catastrophisers (32%) and clinically significant catastrophisers (13%); and, for mental health (SF36 MCS) they were good mental health (40%), moderately low mental health (42%) and severely low mental health (18%). All groups showed no further recovery beyond 12 months after injury. The significant baseline predictors of the severe disability trajectory were: lower (that means worse) bodily pain scores (SF 36 BPS) (p<=0.01); high pain catastrophising (p<=0.01); and, self-reported fair or poor general health (p=0.03). Conditional probabilities for group membership showed that the three trajectories for both PCS and FRI were linked. Dual membership was high for the mild disability and mild pain catastrophising trajectories and, for the severe disability and clinically significant pain catastrophising trajectories. CONCLUSIONS: There is a strong and plausible association between severe disability, clinical levels of pain catastrophising and low mental health. Claimants can be identified at claim notification based on three estimated recovery trajectories. Claim and clinical interventions can be targeted to the profile within each recovery trajectory. PMID- 26372234 TI - Best practices for perinatal palliative care. PMID- 26372235 TI - Electronic forms trump paper for surgical scheduling. PMID- 26372236 TI - Learning the basics of APA Style. PMID- 26372237 TI - Clinical nurses lead the charge with EHR. PMID- 26372240 TI - Defusing bigotry at the bedside. PMID- 26372242 TI - A nurse's journey through living kidney donation. PMID- 26372243 TI - The other side of the stethoscope. PMID- 26372244 TI - Reflections from an ROTC nursing student. PMID- 26372245 TI - Can being ageist harm your older adult patients? PMID- 26372246 TI - A closer look at listeriosis. PMID- 26372249 TI - Correction: Defined Nutrient Diets Alter Susceptibility to Clostridium difficile Associated Disease in a Murine Model. PMID- 26372250 TI - Maternal factors in the origin of isolated anorectal malformations - a population based case-control study. AB - OBJECTIVE: In most patients affected by isolated anorectal malformation (IARM), the etiology is unknown. Thus, the aim of this study was to analyze the possible role of maternal risk factors in the origin of IARM. METHODS: The study samples included 231 cases with IARM, 361 matched and 38 151 population controls without any defect in the population-based large dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996. Cases with IARM were evaluated in the function of maternal diseases and related drug use. RESULTS: The findings of this case-control study suggested that cases with IARM have an obvious male excess. The mothers of cases with IARM had a lower incidence of severe nausea and vomiting in pregnancy and a higher incidence of acute infectious diseases in the urinary tract. CONCLUSIONS: Lack of nausea and vomiting in pregnancy and the higher incidence of urinary tract infections may have a role in the development of IARM. PMID- 26372251 TI - The effect of Transition to Specialty Practice Programs on Australian emergency nurses' professional development, recruitment and retention. AB - BACKGROUND: To date, emergency nursing Transition to Specialty Practice Program (TSPP) evaluations have been single-site observational studies. The aim of this paper was to examine the professional development, recruitment and retention outcomes of Australian emergency nursing TSPPs. METHODS: An explanatory sequential design was used. Data were collected via online surveys and interviews of emergency Nurse Unit Managers and Nurse Educators. Survey data from EDs with TSPPs and EDs without TSPPs were compared. Qualitative data were analysed using content analysis. RESULTS: Data were collected from 118 EDs, and 13 interviews. TSPPs were offered in 72.1% of EDs. EDs with TSPPs had higher proportions of nurses with postgraduate qualifications (Mdn 28.3% vs. 22.1%, p=0.45) and Clinical Specialists (Mdn 16.4% vs. 6.3%, p=0.04). The median proportion of currently rostered nurses with TSPP completion was 34.2% in EDs with TSPPs introduced in 2000-2005 indicating ED high levels of retention. CONCLUSION: Emergency nursing TSPPs have had a positive effect on nursing professional development, recruitment and retention. To ensure consistency in outcomes and optimise reliability of emergency nursing skills and knowledge, a national emergency nursing TSPP framework is needed. PMID- 26372253 TI - Separating coercion from provision in child welfare: Preventive supports should be accessible without conditions attached. PMID- 26372255 TI - Effect of autoclave sterilization on the cyclic fatigue resistance of thermally treated Nickel-Titanium instruments. AB - AIM: To compare the cyclic fatigue resistance of HyFlex CM, Twisted Files (TF), K3XF, Race, and K3, and evaluate the effect of autoclave sterilization on the cyclic fatigue resistance of these instruments both before and after the files were cycled. METHODOLOGY: Five types of NiTi instruments with similar size 30, .06 taper were selected: HyFlex CM, TF, K3XF, Race and K3. Files were tested in a simulated canal with a curvature of 60 degrees and a radius of 3 mm. The number of cycles to failure of each instrument was determined to evaluate cyclic fatigue resistance. Each type of instruments was randomly divided into four experimental groups: group 1 (n = 20), unsterilized instruments; group 2 (n = 20), pre sterilized instruments subjected to 10 cycles of autoclave sterilization; group 3 (n = 20), instruments tested were sterilized at 25%, 50% and 75% of the mean cycles to failure as determined in group 1, and then cycled to failure; group 4 (n = 20), instruments cycled in the same manner as group 3 but without sterilization. The fracture surfaces of instruments were examined by scanning electron microscopy (SEM). RESULTS: HyFlex CM, TF and K3XF had significantly higher cyclic fatigue resistance than Race and K3 in the unsterilized group 1 (P < 0.05). Autoclave sterilization significantly increased the MCF of HyFlex CM and K3XF (P < 0.05) both before and after the files were cycled. SEM examination revealed a typical pattern of cyclic fatigue fracture in all instruments. CONCLUSIONS: HyFlex CM, TF and K3XF instruments composed of new thermal-treated alloy were more resistant to fatigue failure than Race and K3. Autoclaving extended the cyclic fatigue life of HyFlex CM and K3XF. PMID- 26372254 TI - Trefoil factor 1 expression suppresses Helicobacter pylori-induced inflammation in gastric carcinogenesis. AB - BACKGROUND: Infection with Helicobacter pylori, a high-risk factor for gastric cancer, is frequently associated with chronic inflammation through activation of nuclear factor kappaB (NF-kappaB). Trefoil factor 1 (TFF1) is a constitutively expressed protein in the stomach that has tumor-suppressor functions and plays a critical role in maintaining mucosal integrity. This study investigated the role of TFF1 in regulating the proinflammatory response to H. pylori infections. METHODS: For in vitro studies, immunofluorescence, luciferase reporter assays, Western blots, and quantitative real-time polymerase chain reaction were performed to investigate the activation of NF-kappaB and its target genes in response to infections with H. pylori strains J166 and 7.13. In addition, Tff1 knockout (KO) and Tff1-wild-type mice were used for infections with the H. pylori strain called premouse Sydney strain 1. RESULTS: The reconstitution of TFF1 expression in gastric cancer cells significantly suppressed H. pylori-mediated increases in NF-kappaB-p65 nuclear staining, transcriptional activity, and expression of proinflammatory cytokine genes (tumor necrosis factor alpha, interleukin 1beta, chemokine [C-X-C motif] ligand 5, and interleukin 4 receptor) that were associated with reductions in the expression and phosphorylation of NF kappaB-p65 and IkappaB kinase alpha/beta proteins. The in vivo studies using the Tff1-KO mouse model of gastric neoplasia confirmed the in vitro findings. Furthermore, they demonstrated increases in chronic inflammation scores and in the frequency of invasive gastric adenocarcinoma in the Tff1-KO mice infected with H. pylori versus the uninfected Tff1-KO mice. CONCLUSIONS: These findings underscore an important protective role of TFF1 in abrogating H. pylori-mediated inflammation, a crucial hallmark of gastric tumorigenesis. Therefore, loss of TFF1 expression could be an important step in H. pylori-mediated gastric carcinogenesis. PMID- 26372256 TI - Population pharmacokinetic modeling of cefadroxil renal transport in wild-type and Pept2 knockout mice. AB - 1. Cefadroxil is a broad-spectrum beta-lactam antibiotic that is widely used in the treatment of various infectious diseases. Currently, poor understanding of the drug's pharmacokinetic profiles and disposition mechanism(s) prevents determining optimal dosage regimens and achieving ideal antibacterial responses in patients. In the present retrospective study, we developed a population pharmacokinetic model of cefadroxil in wild-type and Pept2 knockout mice using the nonlinear mixed effect modeling (NONMEM) approach. 2. Cefadroxil pharmacokinetics were best described by a two-compartment model, with both saturable and nonsaturable elimination processes to/from the central compartment. Through this modeling approach, pharmacokinetic parameters in wild-type and Pept2 knockout mice were well estimated, respectively, as follows: volume of central compartment V1 (3.43 versus 4.23 mL), volume of peripheral compartment V2 (5.98 versus 8.61 mL), intercompartment clearance Q (0.599 versus 0.586 mL/min) and linear elimination rate constant K10 (0.111 versus 0.070 min(-1)). Moreover, the secretion kinetics (i.e. V(m1) = 17.6 nmoL/min and K(m1) = 37.1 uM) and reabsorption kinetics (i.e. V(m2) = 15.0 nmoL/min and K(m2) = 27.1 uM) of cefadroxil were quantified in kidney, for the first time, under in vivo conditions. 3. Our model provides a unique tool to quantitatively predict the dose-dependent nonlinear disposition of cefadroxil, as well as the potential for transporter-mediated drug interactions. PMID- 26372257 TI - Tautomerism of Warfarin: Combined Chemoinformatics, Quantum Chemical, and NMR Investigation. AB - Warfarin, an important anticoagulant drug, can exist in solution in 40 distinct tautomeric forms through both prototropic tautomerism and ring-chain tautomerism. We have investigated all warfarin tautomers with computational and NMR approaches. Relative energies calculated at the B3LYP/6-311G++(d,p) level of theory indicate that the 4-hydroxycoumarin cyclic hemiketal tautomer is the most stable tautomer in aqueous solution, followed by the 4-hydroxycoumarin open-chain tautomer. This is in agreement with our NMR experiments where the spectral assignments indicate that warfarin exists mainly as a mixture of cyclic hemiketal diastereomers, with an open-chain tautomer as a minor component. We present a diagram of the interconversion of warfarin created taking into account the calculated equilibrium constants (pK(T)) for all tautomeric reactions. These findings help with gaining further understanding of proton transfer and ring closure tautomerization processes. We also discuss the results in the context of chemoinformatics rules for handling tautomerism. PMID- 26372258 TI - Distal Rectal Skip-Segment Hirschsprung Disease and the Potential for False Negative Diagnosis. AB - In skip-segment Hirschsprung disease (SS-HSCR), an aganglionic segment of bowel, which extends proximally from the distal rectum, is interrupted by a ganglionated "skip segment." Skip segments are usually located far proximal to the rectum where they do not interfere with initial diagnosis, although the possibility of distal SS-HSCR should be considered during interpretation of intraoperative biopsies or patients with atypical postoperative courses. We report 2 cases of SS HSCR with skip areas in the distal rectum, 1 of which led to a false-negative diagnosis by suction rectal biopsy. These 2 cases of SS-HSCR, along with others in the literature, highlight the point that ganglionic skip segments can confuse clinicians and lead to inadequate bowel resection, diagnostic delay, or a false negative diagnosis. The pathogenesis of SS-HSCR is discussed in light of recent discoveries regarding transmesenteric migration of vagal neural crest cells and the role of sacral neural crest cells in hindgut neurodevelopment. PMID- 26372259 TI - Framing Neuro-Glia Coupling in Antiepileptic Drug Design. AB - We delineate perspectives for the design and discovery of antiepileptic drugs (AEDs) with fewer side effects by focusing on astroglial modulation of spatiotemporal seizure dynamics. It is now recognized that the major inhibitory neurotransmitter of the brain, gamma-aminobutyric acid (GABA), can be released through the reversal of astroglial GABA transporters. Synaptic spillover and subsequent glutamate (Glu) uptake in neighboring astrocytes evoke replacement of extracellular Glu for GABA, driving neurons away from the seizure threshold. Attenuation of synaptic signaling by this negative feedback through the interplay of Glu and GABA transporters of adjacent astroglia can result in shortened seizures. By contrast, long-range activation of astroglia through gap junctions may promote recurrent seizures on the model of pharmacoresistant temporal lobe epilepsy. From their first detection to our current understanding, we identify various targets that shape both short- and long-range neuro-astroglia coupling, as these are manifest in epilepsy phenomena and in the associated research promotions of AED. PMID- 26372260 TI - In reference to qualitative synthesis and systematic review of otolaryngology in undergraduate medical education. PMID- 26372261 TI - Assessment of adolescents' victimization, aggression, and problem behaviors: Evaluation of the Problem Behavior Frequency Scale. AB - This study evaluated the Problem Behavior Frequency Scale (PBFS), a self-report measure designed to assess adolescents' frequency of victimization, aggression, and other problem behaviors. Analyses were conducted on a sample of 5,532 adolescents from 37 schools at 4 sites. About half (49%) of participants were male; 48% self-identified as Black non-Hispanic; 21% as Hispanic, 18% as White non-Hispanic. Adolescents completed the PBFS and measures of beliefs and values related to aggression, and delinquent peer associations at the start of the 6th grade and over 2 years later. Ratings of participants' behavior were also obtained from teachers on the Behavioral Assessment System for Children. Confirmatory factor analyses supported a 7-factor model that differentiated among 3 forms of aggression (physical, verbal, and relational), 2 forms of victimization (overt and relational), drug use, and other delinquent behavior. Support was found for strong measurement invariance across gender, sites, and time. The PBFS factors generally showed the expected pattern of correlations with teacher ratings of adolescents' behavior and self-report measures of relevant constructs. (PsycINFO Database Record PMID- 26372262 TI - Assessment of social traits in married couples: Self-reports versus spouse ratings around the interpersonal circumplex. AB - Personality traits predict the quality of intimate relationships, and as a result can be useful additions to assessments of couple functioning. For traits involving social behavior, the affiliation (i.e., warmth, friendliness vs. hostility, quarrelsomeness) and control (i.e., dominance vs. deference, submissiveness) dimensions of the interpersonal circumplex (IPC) are an alternative to the 5-factor model traits of agreeableness and extraversion, given that they may provide a more specific and relevant description of social behavior in the context of couple functioning. The couple context creates an opportunity to supplement commonly used self-reports with informant ratings. Although substantial correlations between self-reports and partner ratings of personality are well-documented, differences between these assessment modalities in levels of affiliation and control have not been examined previously. The present study of 301 middle-aged and older couples addressed this issue by comparing self-reports and spouse ratings, using parallel forms of a measure of the interpersonal circumplex derived from the NEO (Neuroticism-Extraversion-Openness) PI-R (Personality Inventory-Revised). Participants reported lower trait dominance relative to spouses' ratings, and less trait hostility. For dominance, this discrepancy was evident at all levels of marital quality, but for hostility it was particularly apparent among couples reporting low marital quality. The tendency to self-report less dominance relative to ratings by spouses was stronger among women than men. These discrepancies may be important in couple assessment and intervention. (PsycINFO Database Record PMID- 26372263 TI - Does the Over-Claiming Questionnaire measure overclaiming? Absent convergent validity in a large community sample. AB - The Over-Claiming Questionnaire (OCQ) aims to provide a practical and cost effective method of assessing individual differences in the tendency to misrepresent oneself in self-reports. OCQ bias measures have strong theoretical appeal but limited empirical demonstrations of validity. Using a sample of 704 adult community members, we found minimal support for the OCQ as an assessment of misrepresentation. We assessed misrepresentation by comparing self-reports of personality and cognitive ability against other criterion indicators of these trait levels (peer reports of personality and performance on a cognitive ability measure). OCQ bias measures bore no relationship with either of these self criterion discrepancy measures, and were also unassociated with self-deceptive enhancement scores. One OCQ index bore a modest relationship to narcissism. OCQ bias measures were instead consistently and sometimes even highly related to measures of careless responding. However, statistically controlling for careless responding only minimally improved the convergent validity of OCQ bias indices. (PsycINFO Database Record PMID- 26372264 TI - Recent advances in engineering topography mediated antibacterial surfaces. AB - The tendency of bacterial cells to adhere and colonize a material surface leading to biofilm formation is a fundamental challenge underlying many different applications including microbial infections associated with biomedical devices and products. Although, bacterial attachment to surfaces has been extensively studied in the past, the effect of surface topography on bacteria-material interactions has received little attention until more recently. We review the recent progress in surface topography based approaches for engineering antibacterial surfaces. Biomimicry of antibacterial surfaces in nature is a popular strategy. Whereas earlier endeavors in the field aimed at minimizing cell attachment, more recent efforts have focused on developing bactericidal surfaces. However, not all such topography mediated bactericidal surfaces are necessarily cytocompatible thus underscoring the need for continued efforts for research in this area for developing antibacterial and yet cytocompatible surfaces for use in implantable biomedical applications. This mini-review provides a brief overview of the current strategies and challenges in the emerging field of topography mediated antibacterial surfaces. PMID- 26372265 TI - Clinical Validity of hearScreenTM Smartphone Hearing Screening for School Children. AB - OBJECTIVES: The study aimed to determine the validity of a smartphone hearing screening technology (hearScreenTM) compared with conventional screening audiometry in terms of (1) sensitivity and specificity, (2) referral rate, and (3) test time. DESIGN: One thousand and seventy school-age children in grades 1 to 3 (8 +/- 1.1 average years) were recruited from five public schools. Children were screened twice, once using conventional audiometry and once with the smartphone hearing screening. Screening was conducted in a counterbalanced sequence, alternating initial screen between conventional or smartphone hearing screening. RESULTS: No statistically significant difference in performance between techniques was noted, with smartphone screening demonstrating equivalent sensitivity (75.0%) and specificity (98.5%) to conventional screening audiometry. While referral rates were lower with the smartphone screening (3.2 vs. 4.6%), it was not significantly different (p > 0.05). Smartphone screening (hearScreenTM) was 12.3% faster than conventional screening. CONCLUSION: Smartphone hearing screening using the hearScreenTM application is accurate and time efficient. PMID- 26372266 TI - The Effects of Noise and Reverberation on Listening Effort in Adults With Normal Hearing. AB - OBJECTIVES: The purpose of this study was to investigate the effects of background noise and reverberation on listening effort. Four specific research questions were addressed related to listening effort: (A) With comparable word recognition performance across levels of reverberation, what are the effects of noise and reverberation on listening effort? (B) What is the effect of background noise when reverberation time is constant? (C) What is the effect of increasing reverberation from low to moderate when signal to noise ratio is constant? (D) What is the effect of increasing reverberation from moderate to high when signal to noise ratio is constant? DESIGN: Eighteen young adults (mean age 24.8 years) with normal hearing participated. A dual-task paradigm was used to simultaneously assess word recognition and listening effort. The primary task was monosyllable word recognition, and the secondary task was word categorization (press a button if the word heard was judged to be a noun). Participants were tested in quiet and in background noise in three levels of reverberation (T30 < 100 ms, T30 = 475 ms, and T30 = 834 ms). Signal to noise ratios used were chosen individually for each participant and varied by reverberation to address the specific research questions. RESULTS: As expected, word recognition performance was negatively affected by both background noise and by increases in reverberation. Furthermore, analysis of mean response times revealed that background noise increased listening effort, regardless of degree of reverberation. Conversely, reverberation did not affect listening effort, regardless of whether word recognition performance was comparable or signal to noise ratio was constant. CONCLUSIONS: The finding that reverberation did not affect listening effort, even when word recognition performance was degraded, is inconsistent with current models of listening effort. The reasons for this surprising finding are unclear and warrant further investigation. However, the results of this study are limited in generalizability to young listeners with normal hearing and to the signal to noise ratios, loudspeaker to listener distance, and reverberation times evaluated. Other populations, like children, older listeners, and listeners with hearing loss, have been previously shown to be more sensitive to reverberation. Therefore, the effects of reverberation for these vulnerable populations also warrant further investigation. PMID- 26372267 TI - Status of vitamin D, antioxidant enzymes, and antioxidant substances in neonates with neonatal hypoxic-ischemic encephalopathy. AB - OBJECTIVE: To investigate the concentration of vitamin D (VD), glutathione peroxidase (GP), superoxide dismutase (SOD), malondialdehyde (MDA), and advanced oxidation protein products (AOPP) in neonates with hypoxic-ischemic encephalopathy (HIE). MATERIAL AND METHODS: This study was performed prospectively in term neonates treated for HIE. Samples were collected from the neonates in study and control groups at 6-14 h and on day 5 of their lives for 25 OH vitamin D3, antioxidant enzymes including GP and SOD and oxidants substances including MDA and AOPP. RESULTS: This study was performed with 31 term neonates with HIE and 30 healthy term neonates. Maternal VD level was statistically lower in the study group (9.8 +/- 6.8 ng/mL) than the control (16.4 +/- 8.7 ng/mL) (p = 0.002). SOD and MDA levels were significantly high, and VD level was significantly low in the study group on the first day of life (p = 0.001 and p = 0.028, respectively). SOD and GP levels were significantly high in the study group on day 5 (p < 0.05). VD was significantly low in the study group on day 5 and the proportion of subjects with VD below 5 ng/ml was significantly lower in the control group (p= <0.05). CONCLUSION: VD has neuroprotective and antioxidant properties. We detected VD levels were low in infants with HIE and their mothers. This finding may be useful for decreasing of brain damage. PMID- 26372268 TI - Increasing use of 'party drugs' in people living with HIV on antiretrovirals: a concern for patient safety. AB - Use of 'party drugs', a particular set of recreational drugs used in the context of 'ChemSex', is frequent among MSM living with HIV. A recently published observational study showed that more than half of HIV-infected MSM interviewed reported use of illicit substances in the previous 3 months, with frequent concomitant use of three or more drugs. These substances are a combination of 'club drugs' (methylenedioxymethamphetamine, gamma-hydroxybutyrate, ketamine, benzodiazepine) and drugs that are more specifically used in a sexualized context (methamphetamine, mephedrone, poppers and erectile dysfunction agents). Although formal data on pharmacokinetic or pharmacodynamic interactions between recreational drugs and antiretroviral agents are lacking, information regarding potentially toxic interactions can be theorized or sometimes conclusions may be drawn from case studies and cohort observational studies. However, the risk of coadministering party drugs and antiretrovirals should not be overestimated. The major risk for a drug-drug interaction is when using ritonavir-boosting or cobicistat-boosting agents, and maybe some nonnucleoside reverse transcriptase inhibitors. Knowledge of the metabolic pathways of 'party drugs' may help in advising patients on which illicit substances have a high potential for drug-drug interactions, as this is not the case for all. PMID- 26372269 TI - HIV and Ebola virus: two jumped species but not two of a kind. PMID- 26372270 TI - Lack of viral control and development of combination antiretroviral therapy escape mutations in macaques after bone marrow transplantation. AB - OBJECTIVE: We have previously demonstrated robust control of simian/human immunodeficiency virus (SHIV1157-ipd3N4) viremia following administration of combination antiretroviral therapy (cART) in pigtailed macaques. Here, we sought to determine the safety of hematopoietic stem cell transplantation (HSCT) in cART suppressed and unsuppressed animals. DESIGN: We compared disease progression in animals challenged with SHIV 100 days post-transplant, to controls that underwent transplant following SHIV challenge and stable cART-dependent viral suppression. METHODS: SHIV viral load, cART levels, and anti-SHIV antibodies were measured longitudinally from plasma/serum from each animal. Flow cytometry was used to assess T-cell subset frequencies in peripheral blood and the gastrointestinal tract. Deep sequencing was used to identify cART resistance mutations. RESULTS: In control animals, virus challenge induced transient peak viremia, viral set point, and durable suppression by cART. Subsequent HSCT was not associated with adverse events in these animals. Post-transplant animals were challenged during acute recovery following HSCT, and displayed sustained peak viremia and cART resistance. Although post-transplant animals had comparable plasma levels of antiretroviral drugs and showed no evidence of enhanced infection of myeloid subsets in the periphery, they exhibited a drastic reduction in virus-specific antibody production and decreased T-cell counts. CONCLUSIONS: These results suggest that virus challenge prior to complete transplant recovery impairs viral control and may promote drug resistance. These findings may also have implications for scheduled treatment interruption studies in patients on cART during post-HSCT recovery: premature scheduled treatment interruption could similarly result in lack of viral control and cART resistance. PMID- 26372271 TI - The effect of KIR2D-HLA-C receptor-ligand interactions on clinical outcome in a HIV-1 CRF01_AE-infected Thai population. AB - OBJECTIVE: Class I human leukocyte antigen (HLA) alleles interact with both cytotoxic T lymphocytes through their T-cell receptors, and natural killer cells through their killer immunoglobulin-like receptors (KIRs). Compared with the reported protective effect of KIR3DL1/S1-HLA-Bw4 interactions in HIV-infected patients, the effect of KIR2D-HLA-C combinations on HIV control remains unclear. Here, we investigate the effect of KIR2D-HLA-C combinations on HIV disease progression. DESIGN: We performed a cross-sectional and longitudinal analysis of a Thai HIV cohort. METHODS: Two hundred and nine HIV-1 CRF01_AE-infected, treatment-naive Thai patients (CD4 T-cell counts of >200/MUl) and 104 exposed seronegatives were studied. The effect of KIR-HLA receptor-ligand combinations on viral transmission and survival rate was statistically analyzed. RESULTS: We found the following results: higher frequency of patients expressing both KIR2DL3 and HLA-C1 among infected patients compared with exposed seronegative (odds ratio 4.8, P = 0.004), higher viral load in patients expressing HLA-C1 with KIR2DL3 compared with those without this receptor-ligand combination (median 4.8 vs. 4.2 log copies/ml, P = 0.033), higher numbers of KIR2DL3-HLA-C1 interactions was associated with a higher viral load (beta = 0.13, P = 0.039 by linear regression model), and higher mortality rate in carriers of the KIR2DL3-HLA-C1 combination (adjusted hazard ratio 1.9, P = 0.012 by Cox hazard model). CONCLUSION: We have identified a deleterious effect of the KIR2DL3-HLA-C1 receptor-ligand combination on HIV clinical outcomes in a Thai cohort. Further investigation into mechanisms underlying this susceptibility may aid the understanding of the role of natural killer cells in HIV disease control and pathogenesis. PMID- 26372272 TI - Biomarkers of inflammation in HIV-infected Peruvian men and women before and during suppressive antiretroviral therapy. AB - OBJECTIVE: Inflammatory biomarkers associated with cardiovascular disease are elevated in HIV-infected persons. These biomarkers improve with antiretroviral therapy (ART) but do not normalize to values observed in HIV-uninfected adults. Little is known regarding biomarkers of inflammation in HIV-infected Peruvians, in whom an increased burden of infectious diseases may exacerbate inflammation, and women, in whom sex difference may alter inflammation compared with men. METHODS: Peruvians initiating first-line ART were enrolled in a prospective observational study. Individuals with suppression of HIV RNA plasma loads to less than 30 copies/ml when determined quarterly over 24 months of ART, had biomarkers of inflammation and cellular activation measured pre-ART and at 24-months of ART, and evaluated for associations with sex and clinical parameters. RESULTS: Pre-ART high-sensitivity C-reactive protein (hsCRP) values of men were in the high-risk cardiovascular disease category (>3.0 mg/l) more frequently compared with women (P = 0.02); most women's values were in the low/average-risk categories. At 24 months of suppressive ART, hsCRP concentrations decreased in men (P = 0.03), but tended to increase in women, such that the proportion with high-risk hsCRP did not differ by sex. Pre-ART, soluble CD163 concentrations were higher in women compared with men (P = 0.02), and remained higher after 24 months of suppressive ART (P = 0.02). All other inflammatory biomarkers (P < 0.03) decreased across sexes. Biomarker concentrations were not associated with BMI or coinfections. CONCLUSION: Elevated inflammatory biomarkers persisted despite 24 months of suppressive ART in a subset of Peruvians, and to a greater extent in women compared with men. These findings suggest that lifestyle or pharmacologic interventions may be required to optimize the health of HIV-infected Peruvians, particularly women. PMID- 26372273 TI - A frailty index predicts survival and incident multimorbidity independent of markers of HIV disease severity. AB - OBJECTIVES: Aging with HIV is associated with multisystem vulnerability that might be well characterized by frailty. We sought to construct a frailty index based on health deficit accumulation in a large HIV clinical cohort and evaluate its validity including the ability to predict mortality and incident multimorbidity. DESIGN AND METHODS: This is an analysis of data from the prospective Modena HIV Metabolic Clinic cohort, 2004-2014. Routine health variables were screened for potential inclusion in a frailty index. Content, construct, and criterion validity of the frailty index were assessed. Multivariable regression models were built to investigate the ability of the frailty index to predict survival and incident multimorbidity (at least two chronic disease diagnoses) after adjusting for known HIV-related and behavioral factors. RESULTS: Two thousand, seven hundred and twenty participants (mean age 46 +/- 8; 32% women) provided 9784 study visits; 37 non-HIV-related variables were included in a frailty index. The frailty index exhibited expected characteristics and met validation criteria. Predictors of survival were frailty index (0.1 increment, adjusted hazard ratio 1.63, 95% confidence interval 1.05 2.52), current CD4 cell count (0.48, 0.32-0.72), and injection drug use (2.51, 1.16-5.44). Predictors of incident multimorbidity were frailty index (adjusted incident rate ratio 1.98, 1.65-2.36), age (1.07, 1.05-1.09), female sex (0.61, 0.40-0.91), and current CD4 cell count (0.71, 0.59-0.85). CONCLUSION: Among people aging with HIV in northern Italy, a frailty index based on deficit accumulation predicted survival and incident multimorbidity independently of HIV related and behavioral risk factors. The frailty index holds potential value in quantifying vulnerability among people aging with HIV. PMID- 26372274 TI - HIV vasculopathy: role of mononuclear cell-associated Kruppel-like factors 2 and 4. AB - OBJECTIVE: To determine the relationships between Kruppel-like factors (KLF) 2 and 4, immune-activation, and subclinical vascular disease in HIV-infected patients on antiretroviral therapy (ART). DESIGN: Double-blind, randomized, placebo-controlled trial. METHODS: We studied 74 HIV-infected adults on ART enrolled in a randomized clinical trial of statin therapy. KLF2 and KLF4 gene expression was measured by quantitative PCR from peripheral blood mononuclear cells (PBMCs) at baseline and after 24 weeks of 10 mg daily rosuvastatin or placebo. At the same time points, T-cell and monocyte activation were assessed by flow cytometry and vascular health was assessed by cardiac computed tomography and carotid ultrasound. RESULTS: KLF4 expression was negatively correlated with duration of ART (r = -0.351, P = 0.004) and positively correlated with measures of immune activation: proinflammatory monocytes [CD14CD16 (r = 0.343, P = 0.003)], patrolling monocytes [CD14CD16 (r = 0.276, P = 0.017)], and activated CD8 T-lymphocytes [CD8DRCD38 (r = 0.264, P = 0.023)]. KLF2 expression was negatively correlated with subclinical atherosclerosis: mean-mean common carotid artery intima-media thickness (r = -0.231, P = 0.048), mean-max carotid artery intima-media thickness (r = -0.271, P = 0.020), and coronary artery calcium score (r = -0.254, P = 0.029). There were no statistically significant changes in KLF2/4 expression in PBMCs after 24 weeks of rosuvastatin. CONCLUSION: Expression of KLF4 in PBMCs positively correlates with cellular markers of immune activation, whereas KLF2 expression negatively correlates with markers of subclinical atherosclerosis in this HIV-infected population on ART. Additional studies are needed to determine if targeted interventions might alter KLF2/4 expression to reduce inflammation and vascular risk in humans. PMID- 26372275 TI - Identification of HIV-1 genitourinary tract compartmentalization by analyzing the env gene sequences in urine. AB - OBJECTIVE: HIV-1 persists indefinitely in memory CD4 T cells and other long-lived cellular reservoirs despite antiretroviral therapy. Our group had previously demonstrated that HIV-1 can establish a productive infection in renal epithelial cells and that the kidney represents a separate compartment for HIV-1 replication. Here, to better understand the viruses in this unique site, we genetically characterized and compared the viruses in blood and urine specimens from 24 HIV-1 infected patients with detectable viremia. DESIGN AND METHODS: Blood and urine samples were obtained from 35 HIV-1 positive patients. Single genome amplification was performed on HIV-1 env RNA and DNA isolated from urine supernatants and urine-derived cell pellets, respectively, as well as from plasma and peripheral blood mononuclear cell from the same individuals. Neighbor-joining trees were constructed under the Kimura 2-parameter model. RESULTS: We amplified and sequenced the full-length HIV-1 envelope (env) gene from 12 of the 24 individuals, indicating that 50% of the viremic HIV-1-positive patients had viral RNA in their urine. Phylogenetic analysis of the env sequences from four individuals with more than 15 urine-derived env sequences showed that the majority of the sequences from urine formed distinct cluster(s) independent of those peripheral blood mononuclear cell and plasma-derived sequences, consistent with viral compartmentalization in the urine. CONCLUSION: Our results suggest the presence of a distinct HIV compartment in the genitourinary tract. PMID- 26372276 TI - Dysregulated B-cell TLR2 expression and elevated regulatory B-cell frequency precede the diagnosis of AIDS-related non-Hodgkin lymphoma. AB - OBJECTIVES: In antiretroviral therapy (ART)-treated patients, to determine if AIDS-related non-Hodgkin lymphoma (AIDS-NHL) is preceded by: elevated frequency of potentially malignant abnormal activated/germinal center-like B cells, elevated serum prevalence of B-cell stimulatory Toll-like receptor (TLR) ligands resulting from HIV infection-associated microbial translocation, dysregulated B cell TLR expression/signaling, and perturbations in the frequency of immunoregulatory cells. DESIGN: A case-control study nested with a cohort study of HIV-infected women. METHODS: Prediagnostic AIDS-NHL cases (n = 12, collected 1 12 months before diagnosis) and controls (n = 42) from the Women's Interagency HIV Study cohort, were matched for HIV and ART status, age, race, and CD4 lymphocyte count. Serum levels of TLR ligands, the prevalence of malignancy associated abnormal activated/germinal center-like (CD19CD10CD71CD86AID) B cells, TLR2 expression on B cells, expression of TLR2-modulating micro-RNA, and the frequency of regulatory T and B cells were assessed. RESULTS: Diagnosis of AIDS NHL was preceded by a significantly elevated frequency of activated/germinal center-like CD19CD10CD71CD86AID B cells (P = 0.0072), elevated serum prevalence of the TLR2 ligand, and significantly elevated B-cell TLR2 expression (P = 0.0015), positively correlating with the frequency of activated/germinal center like B cells (rho = 0.7273, P = 0.0144). In cases, a purified subset of activated/germinal center-like B cells exhibited decreased expression of microRNAs that modulate TLR2 signaling, including miR-21, 146a, 146b, and 155. Finally, cases also exhibited significantly elevated frequencies of antitumor immunity inhibitory regulatory B cells (P = 0.0024), but not regulatory T cells. CONCLUSIONS: Our findings suggest that increased microbial translocation and dysregulated TLR expression/signaling, coupled with an elevated frequency of regulatory B cells, precede the diagnosis of AIDS-NHL in HIV-infected ART-treated patients. PMID- 26372278 TI - Nonvolitional sex and HIV-related sexual risk behaviours among MSM in the United States. AB - OBJECTIVE: We estimated the prevalence of lifetime nonvolitional sex (NVS) among MSM by demographic characteristics, and characterized its association with HIV related sexual risk behaviours among MSM in the United States. DESIGN: The National Survey of Family Growth (NSFG) is a nationally representative cross sectional survey of the United States. METHODS: NSFG data from recent cycles 2002, and 2006-2010 were weighted and analysed for men aged 18-44 years who reported ever having anal or oral intercourse with another male. Associations of lifetime NVS (forced sex by men or women) and age of first NVS experience (<18 vs. >=18 years), with HIV-related sexual risk behaviour outcomes in the past 12 months (i.e. sex with two or more male sex partners; exchanged sex for money or drugs; sex with IDU; sex with HIV-positive person; sex with two or more female sex partners) were assessed using adjusted prevalence ratios (aPR). RESULTS: An estimated 3 226 872 or 5.8% of men aged 18-44 years were identified as MSM with 24.6% of them reporting ever experiencing NVS. MSM reporting NVS at age 18 years or older were more likely to have had sex with an IDU [aPR = 4.40; 95% confidence interval (95% CI) 1.78-10.88] and exchanged sex for money or drugs (aPR = 2.52; 95% CI 1.17-5.43) in the past 12 months compared with those not reporting NVS. NVS for MSM less than 18 years of age was associated with exchanging sex for money or drugs. CONCLUSION: Effective interventions to raise awareness of NVS among MSM and to offer support for MSM who have experienced NVS are needed. PMID- 26372277 TI - Levels of intracellular HIV-DNA in patients with suppressive antiretroviral therapy. AB - OBJECTIVE: The objective of this study is to study factors associated with HIV DNA levels in chronically infected patients on long-term suppressive antiretroviral therapy (ART). DESIGN: A cross-sectional, multicentre study of patients receiving ART for more than 3 years, HIV-RNA less than 50 copies/ml for more than 2 years and CD4 cell count more than 350 cells/MUl. METHOD: Factors associated with low (<150) or high (>1000), compared with intermediate (150-1000 copies/10 PBMCs) levels of HIV-DNA were investigated using multinomial logistic regression. RESULTS: Five hundred and twenty-two patients who initiated ART during the chronic phase were included (71% male; median peak HIV-RNA: 4.88 log10 copies/ml, CD4 cell count nadir: 222 cells/MUl). Median ART duration was 13 years [interquartile range (IQR) 7-17], viral suppression was 5.7 years (IQR 3.9-8.5) and 66% of the patients never experienced ART failure. Median HIV-DNA was 323 copies/10 PBMCs (IQR, 129-717) with low, intermediate and high levels observed in 28.3, 55.4 and 16.3%, respectively. In multivariable analysis, women were more likely to achieve a low level of HIV-DNA. Each additional year with suppressed HIV-RNA increased the likelihood of low level and decreased the likelihood of high level of HIV-DNA. Peak HIV-RNA higher than 5log10 was always associated with a decreased risk of low and an increased risk of high HIV-DNA. For patients with peak HIV-RNA lower than 5log10, past ART failure was associated with high level of HIV-DNA. CONCLUSION: Chronically HIV-infected patients with long-term suppressive ART can achieve low total HIV-DNA but one over six still presented HIV-DNA above 1000 copies/10 PBMCs despite long-term viral suppression. PMID- 26372279 TI - Characterizing retention in HAART as a recurrent event process: insights into 'cascade churn'. AB - OBJECTIVE: The benefits of HAART rely on continuous lifelong treatment retention. We used linked population-level health administrative data to characterize durations of HAART retention and nonretention. DESIGN: This is a retrospective cohort study. METHODS: We considered individuals initiating HAART in British Columbia (1996-2012). An HAART episode was considered discontinued if individuals had a gap of at least 30 days between days in which medication was prescribed. We considered durations of HAART retention and nonretention separately, and used Cox proportional hazards frailty models to identify demographic and treatment-related factors associated with durations of HAART retention and nonretention. RESULTS: Six thousand one hundred fifty-two individuals were included in the analysis; 81.2% were male, 40.6% were people who inject drugs, and 42.8% initiated treatment with CD4 cell count less than 200 cells/MUl. Overall, 29% were continuously retained on HAART through the end of follow-up. HAART episodes were a median 6.8 months (25th, 75th percentile: 2.3, 19.5), whereas off-HAART episodes lasted a median 1.9 months (1.2, 4.5). In Cox proportional hazards frailty models, durations of HAART retention improved over time. Successive treatment episodes tended to decrease in duration among those with multiple attempts, whereas off-HAART episodes remained relatively stable. Younger age, earlier stages of disease progression, and injection drug use were all associated with shorter durations of HAART retention and longer off-HAART durations. CONCLUSION: Metrics to monitor HAART retention, dropout, and reentry should be prioritized for HIV surveillance. Clinical strategies and public health policies are urgently needed to improve HAART retention, particularly among those at earlier stages of disease progression, the young, and people who inject drugs. PMID- 26372280 TI - Factors associated with abnormal spirometry among HIV-infected individuals. AB - OBJECTIVE: HIV-infected individuals are susceptible to development of chronic lung diseases, but little is known regarding the prevalence and risk factors associated with different spirometric abnormalities in this population. We sought to determine the prevalence, risk factors and performance characteristics of risk factors for spirometric abnormalities among HIV-infected individuals. DESIGN: Cross-sectional cohort study. METHODS: We analyzed cross-sectional US data from the NHLBI-funded Lung-HIV consortium - a multicenter observational study of heterogeneous groups of HIV-infected participants in diverse geographic sites. Logistic regression analysis was performed to determine factors statistically significantly associated with spirometry patterns. RESULTS: A total of 908 HIV infected individuals were included. The median age of the cohort was 50 years, 78% were men and 68% current smokers. An abnormal spirometry pattern was present in 37% of the cohort: 27% had obstructed and 10% had restricted spirometry patterns. Overall, age, smoking status and intensity, history of Pneumocystis infection, asthma diagnosis and presence of respiratory symptoms were independently associated with an abnormal spirometry pattern. Regardless of the presence of respiratory symptoms, five HIV-infected participants would need to be screened with spirometry to diagnose two individuals with any abnormal spirometry pattern. CONCLUSIONS: Nearly 40% of a diverse US cohort of HIV-infected individuals had an abnormal spirometry pattern. Specific characteristics including age, smoking status, respiratory infection history and respiratory symptoms can identify those at risk for abnormal spirometry. The high prevalence of abnormal spirometry and the poor predictive capability of respiratory symptoms to identify abnormal spirometry should prompt clinicians to consider screening spirometry in HIV-infected populations. PMID- 26372281 TI - Using hepatitis C prevalence to estimate HIV epidemic potential among people who inject drugs in the Middle East and North Africa. AB - OBJECTIVES: The objective of this study is to understand the association between HIV and hepatitis C virus (HCV) among people who inject drugs (PWIDs) in the Middle East and North Africa (MENA), and to estimate HIV epidemic potential among PWIDs using HCV prevalence. DESIGN/METHODS: Using data from a systematic review of HIV and HCV among PWID in MENA, we conducted two analyses, stratified by HIV epidemic state: a meta-analysis of the risk ratio of HCV to HIV prevalence (RRHCV/HIV) using DerSimonian-Laird random-effects models, and multivariable linear regression predicting log HIV prevalence. The HCV-HIV association from both analyses was used to estimate HIV prevalence at endemic equilibrium. We compared predicted with current HIV prevalence to classify HIV epidemic potential at country-level as low, medium or high, using predefined criteria. RESULTS: The review identified 88 HCV prevalence measures among PWID in MENA, of which 54 had a paired HIV prevalence measure. The pooled RRHCV/HIV were 16, 4 and 3 in low level, emerging and established HIV epidemics, respectively. There was a significant linear relationship between HCV and HIV at endemic equilibrium (P = 0.002). The predicted endemic HIV prevalence ranged between 8% (Tunisia) and 22% (Pakistan). Of the nine countries with data, five have high and three medium HIV epidemic potential. Only one country, Pakistan, appears to have reached saturation. CONCLUSION: HCV prevalence could be a predictor of future endemic HIV prevalence. In MENA, we predict that there will be further HIV epidemic growth among PWID. The proposed methodology can identify PWID populations that should be prioritized for HIV prevention interventions. PMID- 26372282 TI - Neurocognitive deficits increase risk of poor retention in care among older adults with newly diagnosed HIV infection. AB - OBJECTIVE: To evaluate the role of neurocognitive impairment on retention in care across the lifespan in antiretroviral-naive persons newly diagnosed with HIV. DESIGN: A prospective observational study of 138 antiretroviral-naive newly diagnosed HIV-positive participants who presented to an urban clinic between August 2010 and April 2013. METHODS: All participants underwent a baseline evaluation that included a neuromedical examination and brief neuropsychological test battery. Retention in care was operationalized as attending at least two visits separated by more than 90 days during the 12-month follow-up period. RESULTS: Fifty-five per cent of participants were retained in care over the study observation period. In a logistic regression controlling for ethnicity, there was a significant interaction between age and neurocognitive impairment in predicting retention in care (P = 0.009). Planned post-hoc analyses showed that neurocognitive impairment was associated with a significantly lower likelihood of retention in care among participants aged 50 years and older (P = .007), but not among younger participants (P > 0.05). CONCLUSION: Extending prior research on antiretroviral adherence and medication management, findings from this study indicate that neurocognitive impairment may be an especially salient risk factor for poor retention in care among older adults with newly diagnosed HIV infection. PMID- 26372283 TI - Notes on the road to perfection; use of nevirapine in combination antiretroviral therapy for children with perinatal nevirapine exposure. PMID- 26372284 TI - A cluster of rapid disease progressors upon primary HIV-1 infection shared a novel variant with mutations in the p6gag/pol and pol/vif genes. AB - Few studies have described the etiologic factors associated with rapid AIDS onset during primary HIV-1 infection. Our molecular epidemiological study identified a cluster of individuals infected with HIV-1 variants characterized by novel mutations in the p6 and pol/vif genes during 2011 and 2013 in Osaka, Japan. Individuals positive for the novel HIV-1 variant showed rapid disease progression, suggesting a role of viral mutations in the fostering of the clinical course of HIV-1 infection. PMID- 26372285 TI - Treatment as prevention for HIV: a reality. PMID- 26372286 TI - Raltegravir/nevirapine dual therapy at reduced doses as 'maintenance' treatment in virally suppressed HIV-infected patients. PMID- 26372287 TI - Psychiatric disorders after starting dolutegravir: report of four cases. PMID- 26372288 TI - The Spectrum of beta-Thalassemia Mutations in a Population from the Brazilian Amazon. AB - The spectrum of beta-thalassemia (beta-thal) mutations was investigated for the first time in a cohort of 33 unrelated patients from the Brazilian Amazon attending the Center for Hemotherapy and Hematology of the Para Foundation (HEMOPA), in Belem, the state capital of Para, Northern Brazil. Identification of the beta-thal mutations was made by direct genomic sequencing of the beta-globin gene. Mutations were identified in all patients, corresponding to a spectrum of 10 different point mutations and a total of 37 alleles studied. HBB: c.92 + 5G > A [IVS-I-5 (G > A)], was the most common beta-thal mutation, followed by HBB: c.118C > T [codon 39 (C > T)], HBB: c.-138C > T [-88 (C>T)], HBB: c.92 + 1G > A [IVS-I-1 (G > A)] and HBB: c.92 + 6T > C [IVS-I-6 (T > C)] mutations. These five mutations (four Mediterranean origin and one African origin) accounted for 86.5% of the beta-thal alleles. The profile of beta-thal mutations found in northern Brazil is different from those described in other regions of the country. In the southeast and south, the nonsense mutation HBB: c.118C > T is the most prevalent, followed by HBB: c.93-21G > A [IVS-I-110 (G > A)], whereas in the northeast, HBB: c.92 + 6T > C has been identified as the most common mutation, followed by HBB: c.92 + 1G > A. This heterogeneous geographical distribution is certainly related to the ancestry of Brazilian populations because they have similar genetic backgrounds (European, African and Amerindian), although with slightly different admixture proportions. Furthermore, the European contribution in the southeast and south was largely made up of immigrants of other nationalities, such as Italian and Spanish, in addition to Portuguese. PMID- 26372290 TI - When should stapes surgery be performed in children? PMID- 26372289 TI - Measuring the educational environment on a multidisciplinary hospital service. PMID- 26372291 TI - DEFICITS IN DISENGAGING ATTENTION FROM THREAT PREDICT IMPROVED RESPONSE TO COGNITIVE BEHAVIORAL THERAPY FOR ANXIETY. AB - BACKGROUND: Pretreatment biases in attending toward threat have been shown to predict greater symptom reduction following cognitive behavioral therapy (CBT) for anxiety. Findings to date do not extend to clinical severity of diagnoses and they assess treatment response immediately posttreatment and not at follow-up. Research in this area has also not examined components of vigilance (e.g., engagement, disengagement) or whether these effects are confined to external attention and not attention to internal symptoms of anxiety. METHODS: In the present investigation, 96 adults with a range of anxiety disorders completed a dot probe task to assess threat-related attention biases before and after 12 sessions of CBT. RESULTS: Pretreatment deficits in disengaging attention from external and internal threats, and not the speed of engagement with threat, predicted reductions in clinical severity of diagnoses that were maintained 2 years later. The presence of posttreatment attention biases was not associated with increased clinical severity after treatment. CONCLUSIONS: Pretreatment deficits in disengaging attention from threat may promote better and more durable response to CBT for a range anxiety disorders. PMID- 26372292 TI - Cyanoacrylate medical glue application in intervertebral disc annulus defect repair: Mechanical and biocompatible evaluation. AB - In an attempt to find an ideal closure method during annulus defect repair, we evaluate the use of medical glue by mechanical and biocompatible test. Cyanoacrylate medical glue was applied together with a multilayer microfiber/nanofiber polycaprolactone scaffold and suture in annulus repair. Continuous axial loading and fatigue mechanical test was performed. Furthermore, the in vitro response of mesenchymal stem cell (MSC) to the glue was evaluated by cell viability assay. The in vivo response of annulus tissue to the glue and scaffold was also studied in porcine lumbar spine; histological sections were evaluated after 3 months. Cyanoacrylate glue significantly improved the closure effect in the experimental group with failure load 2825.7 +/- 941.6 N, compared to 774.1 +/- 281.3 N in the control group without glue application (p < 0.01). The experimental group also withstood the fatigue test. No toxic effect was observed by in vitro cell culture and in vivo implantation. On the basis of this initial evaluation, the use of cyanoacrylate medical glue improves closure effect with no toxicity in annulus defect repair. This method of annulus repair merits further effectiveness study in vivo. (c) 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 14-20, 2017. PMID- 26372293 TI - Multipole-preserving quadratures for the discretization of functions in real space electronic structure calculations. AB - Discretizing an analytic function on a uniform real-space grid is often done via a straightforward collocation method. This is ubiquitous in all areas of computational physics and quantum chemistry. An example in density functional theory (DFT) is given by the external potential or the pseudo-potential describing the interaction between ions and electrons. The accuracy of the collocation method used is therefore very important for the reliability of subsequent treatments like self-consistent field solutions of the electronic structure problems. By construction, the collocation method introduces numerical artifacts typical of real-space treatments, like the so-called egg-box error, which may spoil the numerical stability of the description when the real-space grid is too coarse. As the external potential is an input of the problem, even a highly precise computational treatment cannot cope this inconvenience. We present in this paper a new quadrature scheme that is able to exactly preserve the moments of a given analytic function even for large grid spacings, while reconciling with the traditional collocation method when the grid spacing is small enough. In the context of real-space electronic structure calculations, we show that this method improves considerably the stability of the results for large grid spacings, opening up the path towards reliable low-accuracy DFT calculations with a reduced number of degrees of freedom. PMID- 26372295 TI - Evidence of reactive gene-environment correlation in preschoolers' prosocial play with unfamiliar peers. AB - The development of prosocial behaviors during the preschool years is essential for children's positive interactions with peers in school and other social situations. Although there is some evidence of genetic influences on prosocial behaviors, very little is known about how genes and environment, independently and in concert, affect prosocial behaviors in young children. This study of 126 twin and sibling pairs examined 5-year-old preschool children's positive behaviors (prosocial and easy-going) while playing freely with an unfamiliar, same-age, same-sex peer. Children were randomly paired, allowing us to rule out passive (parent-influenced environment) and active (child-driven peer choices) gene-environment correlations as potential influences on the results. We found evidence of reactive gene-environment correlation, demonstrating that children who are genetically more likely to act prosocially and to be temperamentally outgoing appear to evoke more prosocial and easy-going behaviors from an unfamiliar peer. We also found that both dominant genetic and nonshared environmental factors were significant influences on preschoolers' prosocial play behaviors, but that neither genetic nor shared environmental factors were significant for easy-going play behaviors. These findings shed important light on influences of prosocial behaviors in preschoolers. Via inherited tendencies, preschool children's positive behaviors evoke similar positive behaviors from their play peers. Given that prosocial behaviors are preludes to a large range of important socially appropriate behaviors, prosocial children should be encouraged to interact with their peers to potentially create a more positive atmosphere within social contexts. PMID- 26372296 TI - Towards a genuinely user-centred evaluation of harm reduction and drug treatment programmes: A further proposal. PMID- 26372294 TI - Multimodal sex-related differences in infant and in infant-directed maternal behaviors during months three through twelve of development. AB - Using the concepts of sensory and affective experience, this work relates the concepts of socialization and cognitive development to the embodiment of gender in the human infant. Evidence obtained from biweekly observations from 30 children and their mothers observed from age 3 months to age 12 months revealed measurable sex-related differences in how mothers handle and touch their infants. This work offers novel approaches to visualizing combinations of behaviors with the aim of encouraging researchers to think in terms of suites of action rather than singular sensory or motor systems. New avenues of research into the mechanisms which produce sex-related differences in behavior are suggested. PMID- 26372298 TI - The editor's dilemma: how DSM politics are turning psychiatry into a pseudoscience. PMID- 26372297 TI - Ventriculostomy-related infections: The performance of different definitions for diagnosing infection. AB - INTRODUCTION: Comparison of rates of ventriculostomy-related infections (VRIs) across institutions is difficult due to the lack of a standard definition. We sought to review published definitions of VRI and apply them to a test cohort to determine the degree of variability in VRI diagnosis. MATERIALS AND METHODS: We conducted a PubMed search for definitions of VRI using the search strings "ventriculostomy-related infection" and "ventriculostomy-associated infection." We applied these definitions to a test cohort of 18 positive cerebrospinal fluid (CSF) cultures taken from ventriculostomies at two institutions to compare the frequency of infection using each definition. RESULTS: We found 16 unique definitions of VRI. When the definitions were applied to the test cohort, the frequency of infection ranged from 22 to 94% (median 61% with interquartile range (IQR) 56-74%). The concordance between VRI diagnosis and treatment with VRI directed antibiotics for at least seven days ranged from 56 to 89% (median: 72%, IQR: 71-78%). CONCLUSIONS: The myriad of definitions in the literature produce widely different frequencies of infection. In order to compare rates of VRI between institutions for the purposes of qualitative metrics and research, a consistent definition of VRI is needed. PMID- 26372299 TI - THE CLINICAL AND METABOLIC CHARACTERISTICS OF YOUNG-ONSET KETOSIS-PRONE TYPE 2 DIABETES IN CHINA. AB - OBJECTIVE: To investigate the prevalence and clinical characteristics of ketosis prone type 2 diabetes (KPD) in Chinese patients with young-onset diabetes. METHODS: A total of 238 young diabetic patients were recruited from our inpatient department from January 1, 2012, to December 28, 2014. KPD was defined as diabetes without precipitating illness and with the presence of ketosis or diabetic ketoacidosis in the absence of autoantibodies at the time of diagnosis. We reviewed the clinical characteristics and disease progression of this group of patients. RESULTS: Eighteen patients fulfilled the criteria for KPD, and the prevalence of patients with KPD was 7.6%. The mean (SD) age of the KPD group at the time of diagnosis of diabetes was 27.6 (4.85) years, and these patients were predominantly male (male to female ratio, 8:1) and had a high proportion of obesity and new-onset diabetes and a strong family history of diabetes. beta-Cell function in the KPD group was intermediate between type 1 and type 2 diabetes. Patients with KPD had the highest levels of glycated hemoglobin, triglycerides, total cholesterol, and free fatty acids and the lowest levels of high-density lipoprotein. After 3 to 12 months of follow-up, 17 of 18 patients with KPD (94.4%) were able to discontinue insulin therapy, and 11 patients (61.1%) were managed with diet or exercise alone. CONCLUSION: KPD patients accounted for 7.6% of the diabetic patients requiring admission to a large urban hospital in China, with an age of onset of diabetes of <=35 years. These patients are more likely to be male, have abnormal lipid metabolism, and have more reversible beta-cell dysfunction. PMID- 26372300 TI - SERIAL NECK ULTRASOUND IS MORE LIKELY TO IDENTIFY FALSE-POSITIVE ABNORMALITIES THAN CLINICALLY SIGNIFICANT DISEASE IN LOW-RISK PAPILLARY THYROID CANCER PATIENTS. AB - OBJECTIVE: American Thyroid Association (ATA) low-risk papillary thyroid cancer (PTC) patients without structural evidence of disease on initial posttreatment evaluation have a low risk of recurrence. Despite this, most patients undergo frequent surveillance neck ultrasound (US). The objective of the study was to evaluate the clinical utility of routine neck US in ATA low-risk PTC patients with no structural evidence of disease after their initial thyroid surgery. METHODS: We performed a retrospective review of 171 ATA low-risk PTC patients after total thyroidectomy, with or without radioactive iodine (RAI) ablation, who had a neck US without suspicious findings after therapy. The main outcome measure was a comparison of the frequency of finding false-positive US abnormalities and the frequency of identifying structural disease recurrence. RESULTS: Over a median follow-up of 8 years, 171 patients underwent a median of 5 neck US (range 2-17). Structural recurrence with low-volume disease (<=1 cm) was identified in 1.2% (2/171) of patients at a median of 2.8 years (range 1.6-4.1 years) after their initial diagnosis. Recurrence was associated with rising serum thyroglobulin (Tg) level in 1 of the 2 patients and was detected without signs of biochemical recurrence in the other patient. Conversely, false-positive US abnormalities were identified in 67% (114/171) of patients after therapy, leading to additional testing without identifying clinically significant disease. CONCLUSION: In ATA low-risk patients without structural evidence of disease on initial surveillance evaluation, routine screening US is substantially more likely to identify false-positive results than clinically significant structural disease recurrence. PMID- 26372301 TI - Effect of airway dynamics on the development of larynx cancer. AB - OBJECTIVES/HYPOTHESIS: This study aimed to investigate and measure airway dynamics in anatomical regions where laryngeal cancer was most common in comparison to other regions of the larynx, thereby determining the effect of airway dynamics on the development of laryngeal cancer. STUDY DESIGN AND METHODS: Pulmonary function test airflow data and larynx anatomy measurement data obtained by three-dimensional computed tomography. A healthy male adult was modeled by simulation using the ANSYS program. Analysis of air flow rates, pressure, and force were also made. RESULTS: The supraglottic region average pressure was higher when compared to the subglottic region and clearly lower when compared to the glottic region. The subglottic had the lowest pressure and force levels. The glottic region was the first ranked location for laryngeal cancer; the supraglottic region was the second; and the frequency of laryngeal cancer was much lower in the subglottic region. Our data suggests that the high pressure and force contribute to an increased amount of contact and interaction between toxic particles and mucosa and to increased diffusion of the particles, leading to an increased carcinogenic effect and frequency of cancer. CONCLUSION: Laryngeal cancer was found more frequently in regions with an increased pressure and force stress and reduced air velocity, with a subsequent increase in penetration of the inhaled toxic agents. These findings demonstrate the importance of basic physical fluid mechanics in cancer pathogenesis. LEVEL OF EVIDENCE: NA. Laryngoscope, 126:1136-1142, 2016. PMID- 26372302 TI - Progress in the ecology and conservation of giant pandas. AB - Giant panda (Ailuropoda melanoleuca) conservation is a possible success story in the making. If extinction of this iconic endangered species can be avoided, the species will become a showcase program for the Chinese government and its collaborators. We reviewed the major advancements in ecological science for the giant panda, examining how these advancements have contributed to panda conservation. Pandas' morphological and behavioral adaptations to a diet of bamboo, which bear strong influence on movement ecology, have been well studied, providing knowledge to guide management actions ranging from reserve design to climate change mitigation. Foraging ecology has also provided essential information used in the creation of landscape models of panda habitat. Because habitat loss and fragmentation are major drivers of the panda population decline, efforts have been made to help identify core habitat areas, establish where habitat corridors are needed, and prioritize areas for protection and restoration. Thus, habitat models have provided guidance for the Chinese governments' creation of 67 protected areas. Behavioral research has revealed a complex and efficient communication system and documented the need for protection of habitat that serves as a communication platform for bringing the sexes together for mating. Further research shows that den sites in old-growth forests may be a limiting resource, indicating potential value in providing alternative den sites for rearing offspring. Advancements in molecular ecology have been revolutionary and have been applied to population census, determining population structure and genetic diversity, evaluating connectivity following habitat fragmentation, and understanding dispersal patterns. These advancements form a foundation for increasing the application of adaptive management approaches to move panda conservation forward more rapidly. Although the Chinese government has made great progress in setting aside protected areas, future emphasis will be improved management of pandas and their habitat. PMID- 26372303 TI - Ultrafast Microwave Welding/Reinforcing Approach at the Interface of Thermoplastic Materials. AB - As an attempt to address the needs and tackle the challenges in welding of thermoplastic materials (TPMs), a novel process was performed via short-term microwave (MW) heating of a specific composite, made up of conducting polypyrrole nanogranule (PPy NG) coated carbon and catalyst source precursor (ferrocene) fine particles, at substrate polypropylene (PP) dog bone pieces' interface. Upon vigorous interactions between MWs and electromagnetic absorbent PPy NG coating, the energy was transformed into a large amount of heat leading to a drastic temperature increase that was simultaneously used for the instant carbonization of PPy and the decomposition of fine ferrocene particles, which resulted in multiwalled carbon nanotubes (CNTs) growth at the interface. Meanwhile, the as grown CNTs on the surface conveyed the heat into the adjacent bulk PP and caused locally molten surface layers' formation. Eventually, the light pressure applied at the interface during the heating process squeezed the molten layers together and a new weld was generated. The method is considerably advantageous compared to other alternatives due to (i) its fast, straightforward, and affordable nature, (ii) its applicability at ambient conditions without the need of any extra equipment or chemicals, and also (iii) its ability to provide clean, durable, and functional welds, via precisely controlling process parameters, without causing any thermal distortion or physical alterations in the bulk TPM. Thus, it is believed that this novel welding process will become much preferable for the manufacturing of next-generation TPM composites in large scale, through short term MW heating. PMID- 26372304 TI - Metabolic consequences of polycystic ovary syndrome. AB - Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women and the leading cause of anovulatory infertility. The prevalence of the syndrome ranges between 6 to 15% based on broader Rotterdam diagnostic criteria verses strict NIH diagnostic criteria.1 The condition is characterized by a combination of ovulatory dysfunction, hyperandrogenism and the presence of polycystic ovaries. PCOS has been associated with multiple metabolic alterations and consequences including impaired glucose tolerance, insulin resistance, hyperinsulinemia, type II diabetes, dyslipidemia, metabolic syndrome, obesity and subclinical cardiovascular disease. It remains unclear however if these associations lead to an increased risk of clinically significant long-term cardiovascular disease. Large prospective studies to date have not detected significant differences in overall cardiovascular morbidity and mortality in PCOS. The phenotypical variability in PCOS has made researching each of these associations challenging as different aspects of the syndrome may be contributing, opposing or confounding factors. The ability to detect significant differences in long-term cardiovascular outcomes may also be due to the variable nature of the syndrome. In this review, we attempt to describe a summary of the current literature concerning the metabolic alterations and cardiovascular consequences of polycystic ovary syndrome. PMID- 26372305 TI - Transforming growth factor beta (TGF-beta) isomers influence cell detachment of MG-63 bone cells. AB - Bone repair and wound healing are modulated by different stimuli. There is evidence that Transforming Growth Factor-beta (TGF-beta) super-family of cytokines have significant effects on bone structure by regulating the replication and differentiation of chondrocytes, osteoblasts and osteoclasts. There is also significant evidence that interactions with extracellular matrix molecules influence cell behaviour. In this study cell surface attachment was examined via a trypsinization assay using various TGF-beta isomers in which the time taken to trypsinize cells from the surface provided a means of assessing the strength of attachment. Three TGF-beta isomers (TGF-beta1, 2 and 3), four combined forms (TGF-beta(1+2), TGF-beta(1+3), TGF-beta(2+3) and TGF-beta(1+2+3)) along with four different controls (BSA, HCl, BSA/HCl and negative control) were investigated in this study. The results indicated that treatment with TGF-beta1, 2, 3 and HCl decreased cell attachment, however, this effect was significantly greater in the case of TGF-beta3 (p<0.001) indicating perhaps that TGF-beta3 does not act alone in cell detachment, but instead functions synergistically with signalling pathways that are dependent on the availability of hydrogen ions. Widefield Surface Plasmon Resonance (WSPR) microscope was also used to investigate cell surface interactions. PMID- 26372306 TI - Scope insensitivity in helping decisions: Is it a matter of culture and values? AB - The singularity effect of identifiable victims refers to people's greater willingness to help a single concrete victim compared with a group of victims experiencing the same need. We present 3 studies exploring values and cultural sources of this effect. In the first study, the singularity effect was found only among Western Israelis and not among Bedouin participants (a more collectivist group). In Study 2, individuals with higher collectivist values were more likely to contribute to a group of victims. Finally, the third study demonstrates a more causal relationship between collectivist values and the singularity effect by showing that enhancing people's collectivist values using a priming manipulation produces similar donations to single victims and groups. Moreover, participants' collectivist preferences mediated the interaction between the priming conditions and singularity of the recipient. Implications for several areas of psychology and ways to enhance caring for groups in need are discussed. PMID- 26372307 TI - I can, I do, and so I like: From power to action and aesthetic preferences. AB - The current work tested the hypothesis that power increases reliance on experiences of motor fluency in forming aesthetic preferences. In 4 experiments, participants reported their aesthetic preferences regarding a variety of targets (pictures, movements, objects, and letters). Experiments 1, 2, and 3 manipulated power and motor fluency (via motoric resonance, extraocular muscle training, and dominant hand restriction). Experiment 4 manipulated power and assessed chronic interindividual differences in motor fluency. Across these experiments, power consistently increased reliance on motor fluency in aesthetic preference judgments. This finding was not mediated by differences in mood, judgment certainty, perceived task-demands or task-enjoyment, and derived from the use of motor simulations rather than from power differences in the acquisition of motor experiences. This is the first demonstration suggesting that power changes the formation of preference judgments as a function of motor fluency experiences. The implications of this research for the links between power and action, as well as the understanding of fluency processes are discussed. PMID- 26372308 TI - Observations on Surgeons' Case Selection, Morbidity, and Mortality Following Board Certification. AB - OBJECTIVE: The purpose of this study is to determine if patient selection varies based on years of surgical practice. BACKGROUND: The impact of hospital and surgeon volume as a marker of experience has demonstrated an inverse association with surgical outcomes. However, temporal measures of experience often demonstrate no effect. Additionally, a self-reporting survey demonstrated decreasing case complexity over time, suggesting that changes in patient selection may account for some of these observed discrepancies. METHODS: General surgery cases at a single tertiary care center reported to the American College of Surgeons National Surgical Quality Improvement Program over a 10-year period were identified. Additionally general surgery cases from the ACS NSQIP 2008 PUF data were used to create risk models for any complications, 30-day mortality, or a composite complication or mortality outcome. These models then estimated risk for our local data. Years of experience after American Board of Surgery certification were calculated for each surgeon for each case. Multivariate linear regression, controlling for surgeon clustering, was used to determine the association between years of surgical experience and preoperative risk of complications and mortality. RESULTS: Eighteen thousand six hundred and eighty eight cases were identified from our institution. Surgeons selected patients of increasing operative risk until 15 years of practice before selecting lower risk patients throughout the rest of their career. After adjusting for risk, no association was observed between years from board certification and mortality. However, there was a trend toward decreasing complication rates with increasing experience. CONCLUSIONS: Surgical experience significantly impacts patient selection. Surgeons with over 25 years of experience had lower complication rates. Experience had no impact on mortality. PMID- 26372310 TI - Pre-return-to-work medical consultation for low back pain workers. Good practice recommendations based on systematic review and expert consensus. AB - OBJECTIVES: The pre-return-to-work medical consultation during sick leave for low back pain (LBP) aims at assessing the worker's ability to resume working without risk for his/her health, and anticipating any difficulties inherent to returning to work and job retention. This article summarizes the good practices guidelines proposed by the French Society of Occupational Medicine (SFMT) and the French National Health Authority (HAS), and published in October 2013. METHODS: Good practices guidelines developed by a multidisciplinary and independent task force (24 experts) and peer review committee (50 experts) based on a literature review from 1990 to 2012, according to the HAS methodology. RESULTS: According to the labour regulations, workers can request a medical consultation with their occupational physician at any time. The pre-return-to-work consultation precedes the effective return-to-work and can be requested by the employee regardless of their sick leave duration. It must be scheduled early enough to: (i) deliver reassuring information regarding risks to the lower back and managing LBP; (ii) evaluate prognostic factors of chronicity and prolonged disability in relations to LBP and its physical, social and occupational consequences in order to implement the necessary conditions for returning to work; (iii) support and promote staying at work by taking into account all medical, social and occupational aspects of the situation and ensure proper coordination between the different actors. CONCLUSION: A better understanding of the pre-return-to-work consultation would improve collaboration and coordination of actions to facilitate resuming work and job retention for patients with LBP. PMID- 26372311 TI - An evaluation of the severity and progression of epistaxis in hereditary hemorrhagic telangiectasia 1 versus hereditary hemorrhagic telangiectasia 2. AB - OBJECTIVES/HYPOTHESIS: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular dysplasia whose hallmark symptom is spontaneous recurrent epistaxis. Two major genetic subtypes of this syndrome are HHT1 and HHT2. Severity of epistaxis ranges from occasional low-volume bleeding to frequent large-volume hemorrhage. This study evaluated the severity and progression of epistaxis in HHT1 versus HHT2. STUDY DESIGN: Retrospective cohort study. METHODS: A retrospective chart review was performed for 183 genotyped HHT patients seen at our center from 2010 to 2013. Data collected included epistaxis severity score (ESS), age of epistaxis onset, number and type of treatments, age at which treatments were sought, complete blood count values, ferritin, number of telangiectases, blood transfusions, iron therapy history, and patient demographics. RESULTS: 115 subjects with HHT2 were compared to 68 with HHT1. Subjects with HHT2 had a higher ESS compared to HHT1 (P = .043) and a later age of onset of epistaxis (P = .005). HHT2 subjects were more likely to use oral iron (P = .032) and were more likely to seek interventions to control their epistaxis (P = .029). CONCLUSIONS: HHT2 is associated with more severe epistaxis and a subsequent higher rate of interventions, requiring more aggressive therapy as compared to HHT1. LEVEL OF EVIDENCE: 4. PMID- 26372309 TI - dNP2 is a blood-brain barrier-permeable peptide enabling ctCTLA-4 protein delivery to ameliorate experimental autoimmune encephalomyelitis. AB - Central nervous system (CNS)-infiltrating effector T cells play critical roles in the development and progression of multiple sclerosis (MS). However, current drugs for MS are very limited due to the difficulty of delivering drugs into the CNS. Here we identify a cell-permeable peptide, dNP2, which efficiently delivers proteins into mouse and human T cells, as well as various tissues. Moreover, it enters the brain tissue and resident cells through blood vessels by penetrating the tightly organized blood-brain barrier. The dNP2-conjugated cytoplasmic domain of cytotoxic T-lymphocyte antigen 4 (dNP2-ctCTLA-4) negatively regulates activated T cells and shows inhibitory effects on experimental autoimmune encephalomyelitis in both preventive and therapeutic mouse models, resulting in the reduction of demyelination and CNS-infiltrating T helper 1 and T helper 17 cells. Thus, this study demonstrates that dNP2 is a blood-brain barrier-permeable peptide and dNP2-ctCTLA-4 could be an effective agent for treating CNS inflammatory diseases such as MS. PMID- 26372312 TI - Fine Particulate Matter Constituents, Nitric Oxide Synthase DNA Methylation and Exhaled Nitric Oxide. AB - It remains unknown how fine particulate matter (PM2.5) constituents affect differently the fractional concentration of exhaled nitric oxide (FeNO, a biomarker of airway inflammation) and the DNA methylation of its encoding gene (NOS2A). We aimed to investigate the short-term effects of PM2.5 constituents on NOS2A methylation and FeNO. We designed a longitudinal study among chronic obstructive pulmonary disease (COPD) patients with six repeated health measurements in Shanghai, China. We applied linear mixed-effect models to evaluate the associations. We observed that the inverse association between PM2.5 and methylation at position 1 was limited within 24 h, and the positive association between PM2.5 and FeNO was the strongest at lag 1 day. Organic carbon, element carbon, NO3(-) and NH4(+) were robustly and significantly associated with decreased methylation and elevated FeNO. An interquartile range increase in total PM2.5 and the four constituents was associated with decreases of 1.19, 1.63, 1.62, 1.17, and 1.14 in percent methylation of NOS2A, respectively, and increases of 13.30%,16.93%, 8.97%, 18.26%, and 11.42% in FeNO, respectively. Our results indicated that organic carbon, element carbon, NO3(-) and NH4(+) might be mainly responsible for the effects of PM2.5 on the decreased NOS2A DNA methylation and elevated FeNO in COPD patients. PMID- 26372313 TI - Improved survival after an educational project on colon cancer management in the county of Stockholm--a population based cohort study. AB - INTRODUCTION: Outcomes in rectal cancer have improved dramatically after the introduction of total mesorectal excision (TME). Recently, the TME concept has been transformed into that of complete mesocolic excision (CME) in an attempt to improve prognosis for patients with colon cancer. PATIENTS AND METHODS: Multidisciplinary team (MDT) workshops including the CME concept were held annually between 2004 and 2008 at the Karolinska University Hospital. The workshops focused on preoperative staging, surgery and histopathology and included lectures and live surgery sessions. To compare survival before and after the "Stockholm Colon Cancer Project" all patients diagnosed with a right sided colon cancer between January 1, 2001 and December 31, 2003 (Group 1) and from January 1, 2006 until December 31, 2008 (Group 2) in Stockholm were identified from the Swedish ColoRectal Cancer Registry (SCRCR). RESULTS: The proportion of patients having a tumour resection and the proportion having emergency surgery was higher in Group 1. There were more early tumours and more R0 resections in Group 2. Overall survival in all diagnosed patients and disease free survival after tumour resection was improved in the second time period. DISCUSSION: Surgical teaching programmes may have an impact on the management and outcome in colon cancer. The exact impact from the "Stockholm Colon Cancer Project" cannot be established, however it is likely that it contributed to the improved survival. PMID- 26372314 TI - Effect of Relaxin on Fertility Parameters of Frozen-Thawed Buffalo (Bubalus bubalis) Sperm. AB - The aim of this work was to evaluate the effect of relaxin on fertility parameters of buffalo frozen/thawed sperm. Sperm were incubated in the absence of capacitating agents (negative control), with a known capacitating agent such as heparin (positive control) and with 50 and 100 ng/ml relaxin for 2 and 4 h. Sperm viability, motility, capacitation and the effect of relaxin on the fertilizing ability after heterologous IVF were evaluated. Although viability was not affected, relaxin increased (p < 0.05) sperm motility compared to the negative and positive controls both after 2 h (60.0 +/- 2.0, 60.0 +/- 3.1, 68.3 +/- 1.7 and 69.4 +/- 2.7, respectively, in negative control, positive control, 50 and 100 ng/ml relaxin) and 4 h (55.0 +/- 2.5, 53.3 +/- 3.0, 62.2 +/- 3.0 and 65.0 +/- 3.2, respectively, in negative control, positive control, 50 and 100 ng/ml relaxin) incubation. When sperm were incubated with both 100 ng/ml relaxin and heparin, a decrease (p < 0.01) of pattern A, that is low capacitation level, was observed compared to the negative control both after 2 h (54.4, 34.3 and 36.4%, respectively, in negative control, positive control and 100 ng/ml relaxin) and 4 h (51.9, 35.0 and 34.3%, respectively, in negative control, positive control and 100 ng/ml relaxin). Moreover, an increase (p < 0.01) of pattern EA, that is high capacitation level, was recorded with 100 ng/ml relaxin and heparin compared to the negative control both after 2 h (44.1, 59.3 and 57.7%, respectively, in negative control, positive control and 100 ng/ml relaxin) and after 4 h (43.0, 54.4 and 56.0%, respectively, in negative control, positive control and 100 ng/ml relaxin). Finally, relaxin increased (p < 0.01) cleavage rate compared to the negative control (57.1 +/- 4.4, 72.5 +/- 6.0, 71.4 +/- 5.5 and 73.6 +/- 2.9, respectively, in negative control, positive control, 50 and 100 ng/ml relaxin). In conclusion, relaxin has a beneficial effect on motility, capacitation and fertilizing ability of frozen-thawed buffalo sperm. PMID- 26372315 TI - Nanocalorimetry-coupled time-of-flight mass spectrometry: identifying evolved species during high-rate thermal measurements. AB - We report on measurements integrating a nanocalorimeter sensor into a time-of flight mass spectrometer (TOFMS) for simultaneous thermal and speciation measurements at high heating rates. The nanocalorimeter sensor was incorporated into the extraction region of the TOFMS system to provide sample heating and thermal information essentially simultaneously with the evolved species identification. This approach can be used to measure chemical reactions and evolved species for a variety of materials. Furthermore, since the calorimetry is conducted within the same proximal volume as ionization and ion extraction, evolved species detected are in a collision-free environment, and thus, the possibility exists to interrogate intermediate and radical species. We present measurements showing the decomposition of ammonium perchlorate, copper oxide nanoparticles, and sodium azotetrazolate. The rapid, controlled, and quantifiable heating rate capabilities of the nanocalorimeter coupled with the 0.1 ms temporal resolution of the TOFMS provides a new measurement capability and insight into high-rate reactions, such as those seen with reactive and energetic materials, and adsorption?desorption measurements, critical for understanding surface chemistry and accelerating catalyst selection. PMID- 26372316 TI - Impact of number of prescribed medications on visit-to-visit variability of blood pressure: implications for design of future trials of renal denervation. AB - BACKGROUND: Visit-to-visit blood pressure (BP) variability limits the ability to detect therapeutic effects in hypertension trials. METHODS: To enable future renal denervation trials to detect smaller effect sizes and reliably identify technical improvements, we examined within-patient visit-to-visit BP variability, quantified as SD of change from baseline to final BP (SDDelta), in renal denervation (RDN) trials, trials of BP-lowering tablets, and the VOLTAGE study including 4151 patients. RESULTS: The control arms of RDN trials had more visit to-visit BP variability than tablet trials (SDDelta 23.6 versus 13.5 mmHg; P < 0.001). This might be explained by more prescribed antihypertensive patients in the RDN trials (5.19 +/- 0.13 versus 0.11 +/- 0.11; P < 0.001). In the VOLTAGE study, as the number of medications prescribed rose from 0 to 4, SDDelta rose: 11.9, 11.2, 12.9, 14.4 and 18.0 mmHg (P < 0.001 for trend). Neither baseline BP, nor demographics, nor diabetes independently affected variability. The sample size required for a trial rises proportionally to the square of the number of medications prescribed (rather than just linearly). The relationship between the number of background medications prescribed in a cohort and the excess test retest variance closely fitted this quadratic formula (R = 0.98, P = 0.001). CONCLUSION: Visit-to-visit variability in BP is dramatically larger in patients with more background medications prescribed. If this is due to variable adherence, then future RDN trials, needing to detect smaller effect sizes, would benefit from measures to guarantee adherence. Conceivable measures include enrolling patients on no background medication, preceding each BP measurement with a period off medication, or directly supervising medication intake. PMID- 26372317 TI - Association between cardiorespiratory fitness and submaximal systolic blood pressure among young adult men: a reversed J-curve pattern relationship. AB - OBJECTIVES: Exercise blood pressure is a marker of future cardiovascular morbidity and mortality among individuals with or without high resting BP or any other cardiovascular disease (CVD) signs and symptoms at present. The purpose of this study was to evaluate the association between SBP during submaximal exercise and cardiorespiratory fitness (CRF) among young men. Further, we investigated the trend displayed by submaximal SBP (SSBP) across different levels of CRF. METHODS: Graded exercise test (GXT) using a Modified Bruce protocol was performed on 204 men; SSBP was recorded at each stage of the protocol. Quintiles of CRF were established on the basis of peak oxygen consumption (VO2), with the first quintile (Q) being the lowest fit group and fifth Q the most fit. RESULTS: The mean VO2 peaks in Q 1 through 5 were 32.3, 39.1, 43.4, 48.1 and 55.5 ml/kg per min, respectively. In a model adjusted for age, race, body fat percentage, resting SBP, alcohol intake and smoking, the largest difference in SSBP was observed between men in Q 1 and 2, with 7.6 mmHg (P = 0.05), 9.4 mmHg (P = 0.02) and 9.5 mmHg (P = 0.04) lower SSBP at minutes 6, 8 and 10 of GXT, respectively. SSBP plateaus at Q 3, followed by an increase in the higher Qs, although still lower than Q1. CONCLUSION: There was a reverse J-curve pattern relationship between SSBP and CRF, with the lowest SSBP among men with fair or good CRF and highest among those with poor CRF. VIDEO ABSTRACT: http://links.lww.com/HJH/A538. PMID- 26372318 TI - Short-term effects of instruction in home heating on indoor temperature and blood pressure in elderly people: a randomized controlled trial. AB - BACKGROUND: Increased mortality from cardiovascular disease in winter is partly explained by increased blood pressure (BP) caused by cold exposure. For physicians, instruction in home heating is feasible option to reduce cold exposure, but the effectiveness remains unknown. OBJECTIVES: To determine whether instruction in home heating increases indoor temperatures and decreases ambulatory BP among elderly people, we conducted an open-label, simply randomized, controlled trial in the winters. METHODS: As an intervention, the participants were asked to set the heating device in the living room to start 1 h before estimated rising time with target temperature at 24 degrees C, and to stay in the living room until 2 h after rising as long as possible. Repeatedly measured ambulatory BP, physical activity, and indoor temperatures until 4 h after rising were assessed using multilevel linear regression model with random intercept among individual. RESULTS: A total of 359 eligible participants (mean age +/- standard deviation: 71.6 +/- 6.6) were randomly allocated to the control group (n = 173) and intervention group (n = 186). Intervention significantly increased living room temperature by 2.09 degrees C (95% confidence interval 1.28 2.90), and significantly decreased SBP and DBP by 4.43/2.33 mmHg (95% confidence interval 0.97-7.88/0.08-4.58 mmHg) after adjusting for confounders including age, sex, antihypertensive medication, household income, and physical activity. DISCUSSION: Short-term effect of instruction in home heating showed larger increase of indoor temperature than that of insulation intervention. Significant reduction of BPsuggests the effectiveness on preventing cardiovascular incidence in winter. CONCLUSION: To summarize, instruction in heating significantly decreased BP. PMID- 26372319 TI - Clinical validation for the aldosterone-to-renin ratio and aldosterone suppression testing using simultaneous fully automated chemiluminescence immunoassays. AB - BACKGROUND: As larger numbers of hypertensive patients are screened for primary aldosteronism with the aldosterone-to-renin ratio (ARR), automated analyzers present a practical solution for many laboratories. We report the method-specific ARR cutoff determined with direct, automated chemiluminescence immunoassays allowing the simultaneous measurement of plasma aldosterone concentrations (PACs) and plasma renin concentrations (PRCs). METHODS: Method comparisons to commonly employed assays and tandem mass spectrometry were undertaken. Patients were previously diagnosed based on the local ARR cutoff of 1.2 (ng/dl)/(MUIU/ml) in samples collected in upright seated position. Lack of aldosterone suppression in response to salt load to less than 5 ng/dl confirmed primary aldosteronism. For the new assays, the optimal ARR cutoff was established in 152 patients with essential hypertension, 93 with primary aldosteronism and 147 normotensive patients. Aldosterone suppression was assessed in 73 essential hypertensive and 46 primary aldosteronism patients. RESULTS: PAC and PRC were significantly correlated to values determined with currently available methods (P < 0.001). In patients with primary aldosteronism, patients with essential hypertension and controls, mean (95% confidence interval) PAC was 28.4 (25.4-31.8), 6.4 (5.9-6.9) and 6.2 (5.6-6.9) ng/dl, respectively. In the same groups, PRC was 6.6 (5.6-7.7), 12.9 (11.2-14.8) and 26.5 (22.2-31.5) MUIU/ml. An ARR cutoff of 1.12 provided 98.9% sensitivity and 78.9% specificity. Employing the new assay aldosterone suppression confirmed the diagnosis of primary aldosteronism and essential hypertension using the cutoff of 5 ng/dl. CONCLUSION: Our data demonstrate that the new assays present a convenient alternative for the measurement of PAC and PRC on a single automated analyzer. Availability of these simultaneous assays should facilitate screening and diagnosis of primary aldosteronism. PMID- 26372320 TI - Within-visit BP variability, cardiovascular risk factors, and BP control in central and eastern Europe: findings from the BP-CARE study. AB - INTRODUCTION AND OBJECTIVE: Blood pressure variability (BPV) within 24 h or between visits has been found to represent an independent risk factor for cardiovascular disease. The present study was aimed at determining whether a clinical significance can be given also to the BP variations occurring within a single clinical visit. METHODS: BPV was quantified as coefficient of variation and as standard deviation (SD) of the mean of three systolic SBP values within a visit in the context of a large-cross subclinical survey (BP-CARE) of treated hypertensive patients living in Eastern European countries. The study population was divided into coefficient of variation and SD quartiles and for each quartile a relationship was sought with a large number of cardiovascular risk factors based on patients' history, physical and laboratory examinations. RESULTS: The 6425 hypertensive patients had an age of 59.2 +/- 11 years (mean +/- SD); they were equally distributed by sex and displayed an average SD and coefficient of variation amounting to 5.1 +/- 6.2 mmHg and 3.5 +/- 4.0%, respectively. Compared with the lowest coefficient of variation quartile (Q1), patients in the highest quartile (Q4) showed a significantly greater prevalence of several cardiovascular risk factors, such as age (Q1: 58.5 +/- 11 vs. Q4: 60.3 +/- 11 years, P < 0.001), serum total cholesterol (Q1: 213.0 +/- 46 vs. Q4: 216.4 +/- 51 mg/dl, P < 0.05), blood glucose (Q1: 106.2 +/- 35 vs. Q4: 109.8 +/- 39 mg/dl, P < 0.005), previous cardiovascular events (Q1: 57.4 vs. Q4: 63.9%, P < 0.001), and resistant hypertension (Q1: 26.3 vs. Q4: 34.1%, P < 0.001). They also showed higher office (Q1: 143.2 +/- 18 vs. Q4: 154.3 +/- 19 mmHg, P < 0.001) and 24-h ambulatory SBP values (Q1: 134.8 +/- 17 vs. Q4: 141.2 +/- 18 mmHg, P < 0.001). Similar results were obtained when BPV was expressed as SD. CONCLUSION: Our study provides evidence that greater within-visit BP variabilities are associated with a worse cardiovascular risk profile. This suggests that even this type of BPV may have clinical significance. PMID- 26372321 TI - Sodium-glucose cotransporter-2 inhibitors and blood pressure decrease: a valuable effect of a novel antidiabetic class? AB - Diabetes mellitus is a major issue of public health, affecting more than 300 million people worldwide. Inhibitors of the sodium-glucose cotransporter-2 (SGLT 2) in the renal proximal tubule are a novel class of agents for the treatment of type 2 diabetes mellitus. Inhibition of the SGLT-2 results in reduced glucose reabsorption and improvement in glycemic control. Alongside glucose excretion, SGLT-2 inhibitors also have mild natriuretic and diuretic effects, combining actions of a proximal tubule diuretic and an osmotic diuretic; these properties are expected to lead to small blood pressure (BP) reductions. Clinical studies with dapagliflozin, canagliflozin, empagliflozin, ipragliflozin, luseogliflozin, and tofogliflozin used either as monotherapy or add-on therapy and compared with placebo or active treatment have also examined the effect of these agents on BP as a secondary endpoint. Although with some differences between individual agents, all of the approved SGLT-2 inhibitors provided a mild but meaningful reduction in office SBP and DBP. Recent studies with the use of ambulatory blood pressure monitoring suggest that the magnitude of this BP reduction can be even greater. The aim of this review is to systematically summarize and present the studies reporting the effect of approved SGLT-2 inhibitors on BP. PMID- 26372322 TI - Undiagnosed and uncontrolled hypertension among the adults in rural Bangladesh: findings from a community-based study. AB - OBJECTIVES: This article reports the prevalence and prediction factors of undiagnosed and uncontrolled hypertension among the adults in rural Bangladesh. METHODS: A cross-sectional study of the major noncommunicable disease risk factors was conducted in rural surveillance sites of Bangladesh in 2005. In addition to the self-report questions on risk factors, height, weight, and blood pressure were measured using standard protocols of the WHO STEPwise approach to Surveillance. Undiagnosed hypertension was defined when people reported no hypertension but were found hypertensive when measured, and uncontrolled hypertension was defined when people reported receiving antihypertensive treatment but their blood pressure was above the normal range when measured. RESULTS: The prevalence of undiagnosed hypertension was 11.1%, increasing with age to 22.7% among those aged 60 years and above. Among the hypertensive patients receiving treatment, 54.9% were found to be uncontrolled (34.5% among 25-39 years and 67.9% among 60+ years). Increasing age and higher BMI were significantly positively associated with undiagnosed hypertension in multivariate analysis. Increasing age and more wealth have significant independent association with uncontrolled hypertension. CONCLUSION: High prevalence of undiagnosed hypertension, and more than 50% of the treated hypertension being uncontrolled puts a great challenge ahead for Bangladesh, a resource-poor setting. Regular health check or health screening along with implementation of hypertensive guidelines should be reinforced. PMID- 26372323 TI - Creatine synthesis demands the majority of the bioavailable L-arginine. PMID- 26372324 TI - Reply: To PMID 25882860. PMID- 26372325 TI - Is legacy a myth or a reality? We should know, and we do not. PMID- 26372326 TI - Diastereo- and enantioselective direct vinylogous Michael addition of gamma substituted butenolides to 2-enoylpyridines catalyzed by chiral bifunctional amine-squaramides. AB - The diastereo- and enantioselective direct vinylogous Michael addition reaction of gamma-substituted butenolides to 2-enoylpyridines has been achieved. A range of gamma,gamma-disubstituted butenolide derivatives, bearing two consecutive tri- and tetrasubstituted stereogenic centers, were readily obtained in good yields with excellent stereoselectivities (up to >99 : 1 dr and >99% ee). PMID- 26372327 TI - Using social media for knowledge translation, promotion of evidence-based medicine and high-quality information on health. AB - Knowledge translation activities may be targeted towards all participants in healthcare practices, including patients, consumers, and policy makers. Hereby, use of social media, namely social network Facebook, as a tool for knowledge translation, promotion of evidence-based medicine and high-quality information on health is described. In March 2013, a Facebook page of the Croatian Cochrane Branch was created and its main content are translated plain language summaries (PLS) of the systematic reviews produced by The Cochrane Collaboration. Since the page was created it has gained 1441 followers, mostly from Croatia and neighboring countries with similar language. Most of the page followers are women aged 25 to 44 and the most popular content is related to pregnancy, childbirth and breastfeeding. Page followers are lay persons, health professionals and journalists, who further disseminate the page content. In summary, social media enables multiple possibilities to engage with target audience and to disseminate the evidence-based medicine content. This article is protected by copyright. All rights reserved. PMID- 26372328 TI - Subclassification of small bowel Crohn's disease using magnetic resonance enterography: a review using evidence-based medicine methodology. AB - Magnetic resonance enterography (MRE) has a growing role in imaging small bowel Crohn's disease (SBCD), both in diagnosis and assessment of treatment response. Certain SBCD phenotypes respond well to biologic therapy and others require surgery; MRE has an expanding role in triaging these patients. In this review, we evaluate the MRE signs that subclassify SBCD using evidence-based medicine (EBM) methodology and provide a structured approach to MRE interpretation. PMID- 26372329 TI - Thiourea-based spacers in potent divalent inhibitors of Pseudomonas aeruginosa virulence lectin LecA. AB - A new divalent highly potent inhibitor of the Pseudomonas aeruginosa lectin and virulence factor LecA was prepared. It contains two thiourea linkages which were found to be in the Z,Z isomeric form. This brings the spacer into an elongated conformation required to bridge the two binding sites, which results in the chelating binding mode responsible for the high potency. PMID- 26372330 TI - Self-Assembled, Iridescent, Crustacean-Mimetic Nanocomposites with Tailored Periodicity and Layered Cuticular Structure. AB - Natural high-performance materials inspire the pursuit of ordered hard/soft nanocomposite structures at high fractions of reinforcements and with balanced molecular interactions. Herein, we develop a facile, waterborne self-assembly pathway to mimic the multiscale cuticle structure of the crustacean armor by combining hard reinforcing cellulose nanocrystals (CNCs) with soft poly(vinyl alcohol) (PVA). We show iridescent CNC nanocomposites with cholesteric liquid crystal structure, in which different helical pitches and photonic band gaps can be realized by varying the CNC/PVA ratio. We further show that multilayered crustacean-mimetic materials with tailored periodicity and layered cuticular structure can be obtained by sequential preparation pathways. The transition from a cholesteric to a disordered structure occurs for a critical polymer concentration. Correspondingly, we find a transition from stiff and strong mechanical behavior to materials with increasing ductility. Crack propagation studies using scanning electron microscopy visualize the different crack growth and toughening mechanisms inside cholesteric nanocomposites as a function of the interstitial polymer content for the first time. Different extents of crack deflection, layered delamination, ligament bridging, and constrained microcracking can be observed. Drawing of highly plasticized films sheds light on the mechanistic details of the transition from a cholesteric/chiral nematic to a nematic structure. The study demonstrates how self-assembly of biobased CNCs in combination with suitable polymers can be used to replicate a hierarchical biological structure and how future design of these ordered multifunctional nanocomposites can be optimized by understanding mechanistic details of deformation and fracture. PMID- 26372331 TI - Broadband Multifunctional Efficient Meta-Gratings Based on Dielectric Waveguide Phase Shifters. AB - Molding the wavefront of light is a basic principle of any optical design. In conventional optical components such as lenses and waveplates, the wavefront is controlled via propagation phases in a medium much thicker than the wavelength. Metasurfaces instead typically produce the required phase changes using subwavelength-sized resonators as phase shift elements patterned across a surface. This "flat optics" approach promises miniaturization and improved performance. Here we introduce metasurfaces which use dielectric ridge waveguides (DRWs) as phase shift elements in which the required phase accumulation is achieved via propagation over a subwavelength distance. By engineering the dispersive response of DRWs, we experimentally realize high resolving power meta gratings with broadband (lambda = 1.2-1.7 MUm) and efficient routing (splitting and bending) into a single diffraction order, thus overcoming the limits of blazed gratings. In addition, we demonstrate polarization beam splitting capabilities with large suppression ratios. PMID- 26372332 TI - Preparation of TiO2-supported twinned gold nanoparticles by CO treatment and their CO oxidation activity. AB - We found that twinned gold nanoparticles (T-AuNPs) are generated at a high probability by CO treatment of TiO2-supported Au(iii) at room temperature. Because of the formation of T-AuNPs, the Au/TiO2 prepared by the CO treatment showed higher catalytic activity for CO oxidation than Au/TiO2 prepared by conventional H2 treatment. PMID- 26372334 TI - Epoxy Based Ink as Versatile Material for Inkjet-Printed Devices. AB - Drop on Demand inkjet printing is an attractive method for device fabrication. However, the reliability of the key printing steps is still challenging. This explains why versatile functional inks are needed. Epoxy based ink described in this study could solve this critical issue because it can be printed with low drawbacks (satellites droplets, long-lived filaments, etc.). Moreover, a wide concentration range of solute allows the fabrication of films from thin to high aspect ratio. Optimizing experimental parameters (temperature, overlap) and ink composition (single or cosolvent) is useful to tune the film profile. As a result, many shapes can be obtained such as donuts or hemispherical caps for a droplet and smooth or wavy shape for a thin film. This study demonstrates that epoxy based versatile ink can be used in numerous fields of applications (organic electronics, optics, sensors, MEMS, etc.). To prove this assertion, organic field effect transistors and light emitting films have been fabricated. PMID- 26372333 TI - Partial Mesorectal Excision for Rectal Adenocarcinoma: Morbidity and Oncological Outcome. AB - INTRODUCTION: The surgical approach for the treatment of tumors of the upper third of the rectum remains controversial. Several publications have shown that partial excision of the mesorectum (PME) with division of the mesorectum and rectum 5 cm below the tumor could be a reasonable approach although total mesorectal excision (TME) is still considered the gold standard for all rectal cancers in many studies. We aimed to assess the specifics risks of anterior resection with PME and colorectal anastomosis (CRA) in rectal cancer. PATIENTS AND METHODS: Files of all of the patients who underwent a PME between 2000 and 2011 were reviewed in consecutive order. Complications that occurred within 3 months after surgery, oncological outcome, local and distant recurrences, and survival were assessed. RESULTS: One hundred seventy-two patients had a PME with CRA of whom 49 (28.5%) had a dysfunctional stoma. Grade III to IV complications occurred in 18 (10.5%) patients and 2 (1.2%) died. Thirteen (7.6%) developed an anastomotic leakage, and 5 (2.9%) resulted with a permanent stoma. Mean follow-up was 151 months (range, 0-151 months). The 5-year local recurrence rate was 5.3%. The 5-year overall and disease-free survival assessed in the 147 patients without synchronous metastasis were 93.2% and 79.7%, respectively. CONCLUSION: Partial excision of the mesorectum can be performed safely, in 1 stage in many patients, with a low risk of definitive stoma. The local recurrence and the survival rates that we observed indicate that the prognosis is not altered compared with TME. Therefore, PME can be recommended in the treatment of upper and some mid rectal tumors. PMID- 26372335 TI - Estimation of activation energy for electroporation and pore growth rate in liquid crystalline and gel phases of lipid bilayers using molecular dynamics simulations. AB - Molecular dynamics simulations of electroporation in POPC and DPPC lipid bilayers have been carried out at different temperatures ranging from 230 K to 350 K for varying electric fields. The dynamics of pore formation, including threshold field, pore initiation time, pore growth rate, and pore closure rate after the field is switched off, was studied in both the gel and liquid crystalline (Lalpha) phases of the bilayers. Using an Arrhenius model of pore initiation kinetics, the activation energy for pore opening was estimated to be 25.6 kJ mol( 1) and 32.6 kJ mol(-1) in the Lalpha phase of POPC and DPPC lipids respectively at a field strength of 0.32 V nm(-1). The activation energy decreases to 24.2 kJ mol(-1) and 23.7 kJ mol(-1) respectively at a higher field strength of 1.1 V nm( 1). At temperatures below the melting point, the activation energy in the gel phase of POPC and DPPC increases to 28.8 kJ mol(-1) and 34.4 kJ mol(-1) respectively at the same field of 1.1 V nm(-1). The pore closing time was found to be higher in the gel than in the Lalpha phase. The pore growth rate increases linearly with temperature and quadratically with field, consistent with viscosity limited growth models. PMID- 26372336 TI - Hypothesis: Urbanization and exposure to urban heat islands contribute to increasing prevalence of kidney stones. AB - The prevalence of kidney stones is increasing worldwide. Various etiologies may in part explain this observation including increased prevalence of diabetes, obesity and the metabolic syndrome, increased dietary protein and salt content, and decreased dietary dairy products. We hypothesize an additional and novel potential contributor to increasing kidney stone prevalence: migration to urban settings, or urbanization, and resultant exposure of the population to the higher temperatures of urban heat islands (UHIs). Both urbanization and exposure to UHIs are worldwide, continuous trends. Because the difference in temperature between rural and urban settings is greater than the increase in temperature caused by global warming, the potential effect of urbanization on stone prevalence may be of greater magnitude. However, demonstration of a convincing link between urbanization and kidney stones is confounded by many variables simultaneously affected by migration to cities, such as changes in occupation, income, and diet. No data have yet been published supporting this proposed association. We explore the plausibility and limitations of this possible etiology of increasing kidney stone prevalence. PMID- 26372337 TI - Amount of Time to Eat Lunch Is Associated with Children's Selection and Consumption of School Meal Entree, Fruits, Vegetables, and Milk. AB - BACKGROUND: There are currently no national standards for school lunch period length and little is known about the association between the amount of time students have to eat and school food selection and consumption. OBJECTIVE: Our aim was to examine plate-waste measurements from students in the control arm of the Modifying Eating and Lifestyles at School study (2011 to 2012 school year) to determine the association between amount of time to eat and school meal selection and consumption. DESIGN: We used a prospective study design using up to six repeated measures among students during the school year. PARTICIPANTS/SETTING: One thousand and one students in grades 3 to 8 attending six participating elementary and middle schools in an urban, low-income school district where lunch period lengths varied from 20 to 30 minutes were included. MAIN OUTCOME MEASURES: School food selection and consumption were collected using plate-waste methodology. STATISTICAL ANALYSES PERFORMED: Logistic regression and mixed-model analysis of variance was used to examine food selection and consumption. RESULTS: Compared with meal-component selection when students had at least 25 minutes to eat, students were significantly less likely to select a fruit (44% vs 57%; P<0.0001) when they had <20 minutes to eat. There were no significant differences in entree, milk, or vegetable selections. Among those who selected a meal component, students with <20 minutes to eat consumed 13% less of their entree (P<0.0001), 10% less of their milk (P<0.0001), and 12% less of their vegetable (P<0.0001) compared with students who had at least 25 minutes to eat. CONCLUSIONS: During the school year, a substantial number of students had insufficient time to eat, which was associated with significantly decreased entree, milk, and vegetable consumption compared with students who had more time to eat. School policies that encourage lunches with at least 25 minutes of seated time might reduce food waste and improve dietary intake. PMID- 26372338 TI - Beverage Consumption in Relation to Discretionary Food Intake and Diet Quality among US Adults, 2003 to 2012. AB - BACKGROUND: A majority of Americans consume beverages and discretionary foods foods that are typically low in nutrient value but high in sugar, sodium, fats, and cholesterol-as part of their daily diet, which profoundly impacts their energy balance and nutritional status. OBJECTIVE: This study examined consumption of different types of beverages in relation to discretionary food intake and diet quality among US adults. METHODS: Nationally representative sample of 22,513 adults from the National Health and Nutrition Examination Survey 2003 to 2012 waves were analyzed. The discretionary food category identifies energy-dense, nutrient-poor food products that do not necessarily provide essential nutrients that the human body needs, but can add variety. First-difference estimator addressed confounding bias from time-invariant unobservables (eg, eating habits, taste preferences) by using within-individual variations in diet and beverage consumption between 2 nonconsecutive 24-hour dietary recalls. RESULTS: Approximately 21.7%, 42.9%, 52.8%, 26.3%, and 22.2% of study participants consumed diet beverage, sugar-sweetened beverage (SSB), coffee, tea, and alcohol, respectively, and 90.1% consumed discretionary foods on any given day. Across beverage types, alcohol (384.8 kcal) and SSB (226.2 kcal) consumption was associated with the largest increase in daily total calorie intake; coffee (60.7 kcal) and diet-beverage (48.8 kcal) consumption was associated with the largest increase in daily calorie intake from discretionary foods, and SSB consumption was associated with the largest reduction in daily overall diet quality measured by the Healthy Eating Index 2010. The impact of beverage consumption on daily calorie intake (overall and from discretionary foods) and diet quality differed across individual sociodemographics and body-weight status. The incremental daily calorie intake from discretionary foods associated with diet-beverage consumption was highest in obese adults, and that associated with SSB was highest in normal weight adults. CONCLUSIONS: Interventions to promote healthy eating should assess beverage consumption in the context of overall dietary behavior. PMID- 26372339 TI - Application of Endobronchial Ultrasonography for the Preoperative Detecting Recurrent Laryngeal Nerve Lymph Node Metastasis of Esophageal Cancer. AB - BACKGROUND: The preoperative detection of recurrent laryngeal nerve lymph node (RLN LN) metastasis provides important information for the treatment of esophageal cancer. We investigated the possibility of applying endobronchial ultrasonography (EBUS) with conventional preoperative endoscopic ultrasonography (EUS) and computerized tomography (CT) examination to evaluate RLN LN metastasis in patients with esophageal cancer. METHODS: A total of 115 patients with advanced thoracic esophageal cancer underwent EBUS examinations. Patients also underwent EUS and CT imaging as reference diagnostic methods. Positron emission tomography /computed tomography (PET/CT) was also introduced in partial patients as reference method. The preoperative evaluation of RLN LN metastasis was compared with the surgical and pathological staging in 94 patients who underwent radical surgery. RESULTS: The sensitivities of the preoperative evaluations of RLN LN metastasis by EBUS, EUS and CT were 67.6%, 32.4% and 29.4%, respectively. The sensitivity of EBUS was significantly different from that of EUS or CT, especially in the detection of right RLN LNs. In addition, according to the extra data from reference method, PET/CT was not superior to EBUS or EUS in detecting RLN LN metastasis. Among all 115 patients, 21 patients who were diagnosed with tracheal invasions by EUS or EBUS avoided radical surgery. Another 94 patients who were diagnosed as negative for tracheobronchial tree invasion by EUS and EBUS had no positive findings in radical surgery. CONCLUSIONS: EBUS can enhance the preoperative sensitivity of the detection of RLN LN metastasis in cases of thoracic esophageal cancer and is a useful complementary examination to conventional preoperative EUS and CT, which can alert thoracic surgeons to the possibility of a greater range of preoperative lymph node dissection. EBUS may also indicate tracheal invasion in cases of esophageal stricture. PMID- 26372340 TI - An Evidence-Based Approach To Diagnosis And Management Of Subarachnoid Hemorrhage In The Emergency Department. AB - Aneurysmal subarachnoid hemorrhage accounts for a small percentage of strokes, but it is a significant contributor to the morbidity rate. The diagnosis is challenging and has devastating consequences if it is missed. Accurate initial diagnosis and management are critical to the outcome of the disease. The emergency clinician must have a high index of suspicion and a judicious approach to evaluating the chief complaint of patients with spontaneous subarachnoid hemorrhage (ie, headache). This review evaluates the literature and current evidence, including controversies and recent American Heart Association guidelines, to support a best-practice approach to the diagnosis and treatment of patients with spontaneous subarachnoid hemorrhage. PMID- 26372341 TI - Characterization of gait in late onset Pompe disease. AB - The skeletal muscle manifestations of late-onset Pompe disease (LOPD) cause significant gait impairment. However, the specific temporal and spatial characteristics of abnormal gait in LOPD have not been objectively analyzed or described in the literature. This pilot study evaluated the gait of 22 individuals with LOPD using the GAITRite(r) temporospatial gait analysis system. The gait parameters were compared to normal reference values, and correlations were made with standard measures of disease progression. The LOPD population demonstrated significant abnormalities in temporospatial parameters of gait including a trend towards decreased velocity and cadence, a prolonged stance phase, prolonged time in double limb support, shorter step and stride length, and a wider base of support. Precise descriptions and analyses of gait abnormalities have much potential in increasing our understanding of LOPD, especially in regards to how its natural history may be modified by the use of enzyme replacement therapy (ERT) and other interventions. Gait analysis may provide a sensitive early marker of the onset of clinical symptoms and signs, offer an additional objective measure of disease progression and the impact of intervention, and serve as a potentially important clinical endpoint. The additional data from comprehensive gait analysis may personalize and optimize physical therapy management, and the clarification of specific gait patterns in neuromuscular diseases could be of clinical benefit in the ranking of a differential diagnosis. PMID- 26372342 TI - Radiation-induced lung damage - Clinical risk profiles and predictive imaging on their way to risk-adapted individualized treatment planning? PMID- 26372343 TI - Considering patient values and treatment preferences enhances patient involvement in rectal cancer treatment decision making. AB - BACKGROUND: The shared decision making (SDM) model states that patients' values and preferences should be clarified to choose a strategy that best fits the patient. This study aimed to assess whether values and preferences of rectal cancer patients are voiced and considered in deciding about preoperative radiotherapy (PRT), and whether this makes patients feel more involved in treatment decision making. METHODS: Pre-treatment consultations of radiation oncologists and patients eligible for PRT were audiotaped (N=90). Tapes were transcribed and coded to identify patients' values and treatment preferences. Patients filled in a post-consultation questionnaire on their perceived involvement in decision making (N=60). RESULTS: Patients' values were voiced for 62/611 of benefits/harms addressed (10%), in 38/90 consultations (42%; maximum 4 values per consultation), and most often related to major long-term treatment outcomes. Patients' treatment preferences were discussed in 20/90 consultations (22%). In 16/90 consultations (18%), the oncologists explicitly indicated to consider patients' values or preferences. Patients perceived a significantly more active role in decision making if their values or preferences had been voiced or considered. CONCLUSIONS: Patients' values and treatment preferences are voiced or considered in a minority of consultations. If they are, this increases patients' perceived involvement in the decision making process. PMID- 26372344 TI - Multinational study exploring patients' perceptions of side-effects induced by chemo-radiotherapy. AB - PURPOSE: We aimed to prospectively assess the incidence, severity and patients' perceptions of side-effects induced by radiotherapy and concomitant weekly cisplatin. PATIENTS AND METHODS: This multinational survey included patients with a diagnosis of gynaecological or head and neck cancer scheduled to receive radiotherapy and concomitant weekly cisplatin. Patients completed a questionnaire prior to anti-cancer treatment and after 3 weeks of treatment. Baseline frequency and severity of symptoms were compared to frequency and severity after 3 weeks of treatment, and patients were asked to rank the five most severe symptoms experienced. RESULTS: An increase in the severity as well as in the mean number of symptoms (18 compared to 24) was observed during treatment. Patients ranked 7 of the 10 most feared baseline symptoms as non-physical, whereas 8 of the 10 most feared symptoms after 3 weeks of treatment were physical. Nausea was ranked as the 5th most severe symptom during treatment, despite 98% of patients receiving antiemetic prophylaxis. CONCLUSION: Patients with head and neck cancer or gynaecological cancer suffer from a number of primarily non-physical symptoms before starting combined chemo-radiotherapy. After 3 weeks of treatment patients score 8 of the 10 most feared symptoms as physical. Future trials focusing on the prevention of side-effects in patients receiving radiotherapy and concomitant chemotherapy are highly warranted. PMID- 26372345 TI - Capturing state-dependent dynamic events of GABAA-receptors: a microscopic look into the structural and functional insights. AB - The gamma-amino butyric acid type A receptors (GABAA-Rs) are the key players in the mammalian brain that meditate fast inhibitory neurotransmission events. The structural integrity of these ligand-gated ion channel controls chloride ion permeability, which in turn monitors important pharmacological functions. Despite ample studies on GABAA-Rs, there was a need for a study on full-length receptor structures, devoted to track structure-function correlations based on their dynamic behavior consideration. We have employed molecular dynamics simulations accompanied by other biophysical methods to shed light on sequential and unaddressed questions like How GABAA-R structure facilitates the entry of GABA molecules at its two orthosteric binding sites? After entry, what structural features and changes monitor site-wise GABA binding differences? In the same context, what are the roles and responsibilities of loops such as C and F? On physiologically relevant time scales, how open to close state transition occurs? How salt bridges such as E155-R207 and E153-R207 maintain state-dependent C-loop structures? In an attempt, our simulation study unravels the complete course of GABA binding-unbinding pathway. This provides us with the relevant understanding of state-dependent dynamic events of GABAA-Rs. PMID- 26372346 TI - Soil Methane Sink Capacity Response to a Long-Term Wildfire Chronosequence in Northern Sweden. AB - Boreal forests occupy nearly one fifth of the terrestrial land surface and are recognised as globally important regulators of carbon (C) cycling and greenhouse gas emissions. Carbon sequestration processes in these forests include assimilation of CO2 into biomass and subsequently into soil organic matter, and soil microbial oxidation of methane (CH4). In this study we explored how ecosystem retrogression, which drives vegetation change, regulates the important process of soil CH4 oxidation in boreal forests. We measured soil CH4 oxidation processes on a group of 30 forested islands in northern Sweden differing greatly in fire history, and collectively representing a retrogressive chronosequence, spanning 5000 years. Across these islands the build-up of soil organic matter was observed to increase with time since fire disturbance, with a significant correlation between greater humus depth and increased net soil CH4 oxidation rates. We suggest that this increase in net CH4 oxidation rates, in the absence of disturbance, results as deeper humus stores accumulate and provide niches for methanotrophs to thrive. By using this gradient we have discovered important regulatory controls on the stability of soil CH4 oxidation processes that could not have not been explored through shorter-term experiments. Our findings indicate that in the absence of human interventions such as fire suppression, and with increased wildfire frequency, the globally important boreal CH4 sink could be diminished. PMID- 26372347 TI - Use of Centrifugal Filter Devices to Concentrate Dengue Virus in Mosquito per os Infection Experiments. AB - Dengue virus (DENV) is an arbovirus transmitted to humans by the bite of infected Aedes mosquitoes. Experimental per os infection of mosquitoes with DENV is usually a preliminary step in virus/vector studies but it requires being able to prepare artificial blood-meals with high virus titers. We report here the convenient use of centrifugal filter devices to quickly concentrate DENV particles in cell-culture supernatants. The median viral titer in concentrated supernatants was 8.50 log10 TCID50/mL. By using these DENV concentrated supernatants to prepare infectious blood-meals in Aedes aegypti per os infection experiments, we obtained a mean mosquito-infection rate of 94%. We also evaluated the use of centrifugal filter devices to recover DENV particles from non infectious blood-meals presented to infected mosquitoes through a feeding membrane to collect their saliva. PMID- 26372348 TI - Factors associated with successful transabdominal sonography-guided dilation and curettage for early cesarean scar pregnancy. AB - OBJECTIVE: To investigate factors associated with successful transabdominal sonography-guided dilation and curettage for the treatment of cesarean scar pregnancy (CSP). METHODS: In a retrospective study, data were reviewed from patients who received transabdominal sonography-guided dilation and curettage (TASDC) as the primary treatment for early CSP at The Second Xiangya Hospital, Changsha, China, between 2009 and 2013. RESULTS: Among 232 patients, 185 (79.7%) women with CSP were successfully treated with TASDC. Among them, 81 (43.8%) required insertion of a Foley catheter into the lower uterine segment to stop bleeding. The complication rate was 37.9% (88/232) and the failure rate was 21.3% (47/232). Overall, 28 (12.1%), 5 (2.2%), and 4 (1.7%) patients with massive intraoperative uterine bleeding were treated with wedge resection of the uterus, hysterectomy, and uterine artery embolization as a secondary treatment, respectively. In binary logistic regression analysis, pregnancy of 7 weeks or less and pregnancy without missed abortion were associated with successful TASDC for patients with CSP (P<0.001). CONCLUSION: Pregnancy of 7 weeks or less and pregnancy without missed abortion were found to be important factors for successful TASDC among patients with CSP. Wedge resection was the main secondary treatment to preserve the uterus and remove gestational tissue among patients with massive bleeding. PMID- 26372349 TI - Outcomes of pregnancy with gestational diabetes mellitus. AB - OBJECTIVE: To compare pregnancy outcomes between women with gestational diabetes mellitus (GDM) and those with low-risk pregnancies during implementation of the GDM practice guideline. METHODS: In a retrospective study, data were compared between women with singleton pregnancies complicated by GDM and control women with singleton low-risk pregnancies who delivered at Maharaj Nakorn Chiang Mai Hospital, Thailand, between January 2002 and December 2012. All pregnant women were screened and managed for GDM as recommended by the National Diabetes Data Group. RESULTS: During the study period, 1350 pregnancies with GDM and 20421 low risk pregnancies met the study criteria and were included in the GDM group and the control group, respectively. The incidence of fetal macrosomia-the main outcome-was significantly higher in the GDM group (n=270, 20.0%) than in the control group (n=2776, 3.6%; adjusted odds ratio 1.48, 95% confidence interval 1.28-1.71; P<0.001). The incidences of cesarean delivery, cephalopelvic disproportion, pregnancy-induced hypertension, and shoulder dystocia were also significantly higher in the GDM group (all P<0.05). CONCLUSION: Despite the practice guideline, adverse pregnancy outcomes including fetal macrosomia, cesarean delivery, and pregnancy-induced hypertension, were significantly higher among women with GDM. The findings warrant an effective audit system or improved adherence to the guideline. PMID- 26372350 TI - Prevalence of hyperprolactinemia and thyroid disorders among patients with abnormal uterine bleeding. AB - OBJECTIVE: To evaluate the prevalence of hyperprolactinemia and thyroid disorders among patients with abnormal uterine bleeding (AUB) compared with matched controls. METHODS: In 2013-2014, an observational study of women with AUB (group A) and women with regular menstruation (group B) was undertaken at one center in Egypt and one in the United Arab Emirates. Eligible women were aged 20-35 years and were not obese. Participants underwent clinical examinations, vaginal ultrasonography, office hysteroscopy (in selected cases), and measurement of hormone levels. RESULTS: Hyperprolactinemia was present in 17 (16.2%) of 105 patients in group A and 4 (3.2%) of 125 patients in group B (P=0.009). In group A, a high thyroid-stimulating hormone (TSH) level was observed in 8 (7.6%) patients and low levels of free triiodothyronine/thyroxine were found in 5 (4.8%) patients, compared with 2 (1.6%) patients and 1 (0.8%) patient in group B (P=0.012 and P=0.008, respectively). Polymenorrhea was the most frequent presentation of AUB (n=60 [57.1%]). Five (29.4%) patients with hyperprolactinemia had galactorrhea. In group A, 8 (47.1%) patients with a high TSH had hyperprolactinemia, whereas 1 (1.1%) patient with a high TSH had a normal prolactin value (P=0.008). CONCLUSION: Screening by evaluating prolactin and thyroid hormone levels is recommended for all patients with AUB, even in the absence of galactorrhea. PMID- 26372351 TI - Magnetic resonance imaging findings in tubercular arthritis of elbow. AB - OBJECTIVE: To evaluate magnetic resonance imaging (MRI) features of tubercular involvement of elbow joint. METHODS: Fourteen patients with tubercular arthritis of elbow were evaluated. The following findings were recorded on MRI (n=12): bones involved; erosions, intraosseous abscesses, synovial thickening, and effusion; hypointensity within the thickened synovium on T2-weighted images; and periarticular soft tissue changes. RESULTS: The common abnormalities on MRI were synovial thickening and bone erosions (n=12), soft tissue (n=9)/intraosseous (n=5) abscesses, and T2 hypointensity within the thickened synovium (n=5). CONCLUSIONS: A diagnosis of elbow tuberculosis should be considered if there is a combination of findings involving bone and soft tissue. PMID- 26372352 TI - Uterine artery embolization for symptomatic fibroids in postmenopausal women. AB - PURPOSE: The aim of the current study was to evaluate the efficacy of uterine artery embolization (UAE) for symptomatic fibroids in postmenopausal women. MATERIALS AND METHODS: Among 900 cases who underwent UAE between 2007 and 2013, a total of 9 postmenopausal women with symptomatic fibroids (n=6) and fibroid with adenomyosis (n=3) were included in this retrospective study. Ages ranged from 49 to 55years (median of 52). The embolic agent was nonspherical polyvinyl alcohol particles. We evaluated 18 uterine arteries in nine patients and compared the size of the uterine artery relative to inferior mesenteric artery (IMA) in preprocedural magnetic resonance (MR) angiography. Magnetic resonance imaging (MRI) was performed before and 3months after UAE. Predominant fibroid and uterine volumes were calculated from MR images. RESULTS: Urinary frequency was the most common symptom, observed in seven patients (77.8%). Of two patients (22.2%) with vaginal bleeding from submucosal myomas, one patient had been on hormone replacement therapy (HRT). One patient underwent UAE due to growing leiomyoma after HRT. All of the 18 uterine arteries were bigger than the corresponding IMAs in MR angiography. Contrast-enhanced MRI revealed complete necrosis of the predominant fibroid in all patients. Eight (88.9%) of the nine participants demonstrated resolution of symptoms. The mean predominant fibroid and uterine volume reduction rates were 39.7% and 36.9%, respectively. CONCLUSIONS: In postmenopausal women, UAE was effective to treat symptomatic fibroids, and it could be considered as an alternative treatment to hysterectomy. PMID- 26372353 TI - The Economics of Epidemic Diseases. AB - Epidemic, infectious, diseases affect a large number of individuals across developing as well as developed countries. With reference to some very simple diffusion models, in this paper we consider how available economic resources could be optimally allocated by health authorities to mitigate, possibly eradicate, the disease. Optimality was defined as the minimization of the long run number of infected people. The main goal of the work has been to introduce a methodology for deciding if it would be best to concentrate resources to prevent contact between individuals and with an external source, or to develop a new treatment for curing the disease, or both. The analysis suggests that this depends on the cost functions, that is the available technology, for controlling the relevant parameters underlying the epidemics as well as on the available financial resources. In the case of the recent Ebola outbreak, the suggestions of the model have been consistent with the policies adopted. PMID- 26372354 TI - Polar Desolvation and Position 226 of Pancreatic and Neutrophil Elastases Are Crucial to their Affinity for the Kunitz-Type Inhibitors ShPI-1 and ShPI-1/K13L. AB - The Kunitz-type protease inhibitor ShPI-1 inhibits human neutrophil elastase (HNE, Ki = 2.35.10-8 M) but does not interact with the porcine pancreatic elastase (PPE); whereas its P1 site variant, ShPI-1/K13L, inhibits both HNE and PPE (Ki = 1.3.10-9 M, and Ki = 1.2.10-8 M, respectively). By employing a combination of molecular modeling tools, e.g., structural alignment, molecular dynamics simulations and Molecular Mechanics Generalized-Born/Poisson-Boltzmann Surface Area free energy calculations, we showed that D226 of HNE plays a critical role in the interaction of this enzyme with ShPI-1 through the formation of a strong salt bridge and hydrogen bonds with K13 at the inhibitor's P1 site, which compensate the unfavorable polar-desolvation penalty of the latter residue. Conversely, T226 of PPE is unable to establish strong interactions with K13, thereby precluding the insertion of K13 side-chain into the S1 subsite of this enzyme. An alternative conformation of K13 site-chain placed at the entrance of the S1 subsite of PPE, similar to that observed in the crystal structure of ShPI 1 in complex with chymotrypsin (PDB: 3T62), is also unfavorable due to the lack of stabilizing pair-wise interactions. In addition, our results suggest that the higher affinity of ShPI-1/K13L for both elastases mainly arises from the lower polar-desolvation penalty of L13 compared to that of K13, and not from stronger pair-wise interactions of the former residue with those of each enzyme. These results provide insights into the PPE and HNE inhibition and may contribute to the design of more potent and/or specific inhibitors toward one of these proteases. PMID- 26372355 TI - Vitamin D Deficiency in Unselected Patients from Swiss Primary Care: A Cross Sectional Study in Two Seasons. AB - BACKGROUND: As published data on 25-hydroxy-cholecalciferol (25(OH)D) deficiency in primary care settings is scarce, we assessed the prevalence of hypovitaminosis D, potential associations with clinical symptoms, body mass index, age, Vitamin D intake, and skin type in unselected patients from primary care, and the extent of seasonal variations of serum 25(OH)D concentrations. METHODOLOGY/PRINCIPAL FINDINGS: 25(OH)D was measured at the end of summer and/or winter in 1682 consecutive patients from primary care using an enzyme-linked immunosorbant assay. Clinical symptoms were assessed by self-report (visual analogue scale 0 to 10), and vitamin D deficiency was defined as 25(OH)D concentrations < 50 nmol/l. 25(OH)D deficiency was present in 995 (59.2%) patients. 25(OH)D deficient patients reported more intense muscle weakness (visual analogue scale 2.7, 95% confidence interval 2.5 to 2.9) and had a higher body mass index (25.9kg/m2, 25.5 to 26.2) than non-deficient patients (2.5, 2.3 to 2.7; and 24.2, 23.9 to 24.5, respectively). 25(OH)D concentrations also weakly correlated with muscle weakness (Spearman's rho -0.059, 95% confidence interval -0.107 to -0.011) and body mass index (-0.156, -0.202 to -0.108). Self-reported musculoskeletal pain, fatigue, and age were not associated with deficiency, nor with concentrations. Mean 25(OH)D concentrations in patients with vitamin D containing medication were higher (60.6 +/- 22.2 nmol/l) than in patients without medication (44.8 +/- 19.2 nmol/l, p < 0.0001) but still below the targeted level of 75 nmol/l. Summer and winter 25(OH)D concentrations differed (53.4 +/- 19.9 vs. 41.6 +/- 19.3nmol/l, p < 0.0001), which was confirmed in a subgroup of 93 patients who were tested in both seasons (p = 0.01). CONCLUSION/SIGNIFICANCE: Nearly 60% of unselected patients from primary care met the criteria for 25(OH)D deficiency. Self-reported muscle weakness and high body mass index were associated with lower 25(OH)D levels. As expected 25(OH)D concentrations were lower in winter compared to summer. PMID- 26372356 TI - Magnified Sediment Export of Small Mountainous Rivers in Taiwan: Chain Reactions from Increased Rainfall Intensity under Global Warming. AB - Fluvial sediment export from small mountainous rivers in Oceania has global biogeochemical significance affecting the turnover rate and export of terrestrial carbon, which might be speeding up at the recognized conditions of increased rainfall intensity. In this study, the historical runoff and sediment export from 16 major rivers in Taiwan are investigated and separated into an early stage (1970-1989) and a recent stage (1990-2010) to illustrate the changes of both runoff and sediment export. The mean daily sediment export from Taiwan Island in the recent stage significantly increased by >80% with subtle increase in daily runoff, indicating more sediment being delivered to the ocean per unit of runoff in the recent stage. The medians of the runoff depth and sediment yield extremes (99.0-99.9 percentiles) among the 16 rivers increased by 6.5%-37% and 62%-94%, respectively, reflecting the disproportionately magnified response of sediment export to the increased runoff. Taiwan is facing increasing event rainfall intensity which has resulted in chain reactions on magnified runoff and sediment export responses. As the globe is warming, rainfall extremes, which are proved to be temperature-dependent, very likely intensify runoff and trigger more sediment associated hazards. Such impacts might occur globally because significant increases of high-intensity precipitation have been observed not only in Taiwan but over most land areas of the globe. PMID- 26372357 TI - Pregnancy outcomes in women with osteogenesis imperfecta. AB - OBJECTIVE: To assess the relationship between osteogenesis imperfecta (OI) type, mode of delivery and outcomes as self-reported by women in the International Osteogenesis Imperfecta (OI) Registry. METHODS: A cross-sectional study using data from 274 women with OI who reported their experience with pregnancy practices, including mode of delivery, number of children, genetic counseling, assisted conception techniques, mean ages at menarche and at menopause, and pregnancy complications. Chi-square analyses were performed to compare pregnancy outcomes, number of children and OI type. Prevalence ratios and 95% confidence intervals were obtained to quantify exposure-outcome relationships. RESULTS: The most common mode of delivery was the sole use of cesarean section (C-section) reported by 55% of the participants. Approximately two-thirds had at least two children. Twenty-nine percent (n = 80) reported pregnancy complications. There was a significant relationship between the mode of delivery and OI type (p < 0.001), genetic counseling (p = 0.010), and number of children (p < 0.0001). There was neither evidence of an association between pregnancy complications and number of children (p = 0.16), OI type (p = 0.27), nor mode of delivery (p = 0.11). CONCLUSIONS: These findings suggested that clinical OI type, pre-natal genetic counseling, and number of children were strong predictors for choosing the mode of delivery. Severity of OI, multiparity, and vaginal delivery were not associated with increased pregnancy complications in this cohort of women with OI. PMID- 26372360 TI - Overview of the mechanisms of induction of labor. AB - Here we provide a brief overview of the natural process of labor and its biochemical, hormonal, and mechanical characteristics that can be exploited in methods employed for induction of labor. PMID- 26372359 TI - Selective Serotonin Reuptake Inhibitors and Violent Crime: A Cohort Study. AB - BACKGROUND: Although selective serotonin reuptake inhibitors (SSRIs) are widely prescribed, associations with violence are uncertain. METHODS AND FINDINGS: From Swedish national registers we extracted information on 856,493 individuals who were prescribed SSRIs, and subsequent violent crimes during 2006 through 2009. We used stratified Cox regression analyses to compare the rate of violent crime while individuals were prescribed these medications with the rate in the same individuals while not receiving medication. Adjustments were made for other psychotropic medications. Information on all medications was extracted from the Swedish Prescribed Drug Register, with complete national data on all dispensed medications. Information on violent crime convictions was extracted from the Swedish national crime register. Using within-individual models, there was an overall association between SSRIs and violent crime convictions (hazard ratio [HR] = 1.19, 95% CI 1.08-1.32, p < 0.001, absolute risk = 1.0%). With age stratification, there was a significant association between SSRIs and violent crime convictions for individuals aged 15 to 24 y (HR = 1.43, 95% CI 1.19-1.73, p < 0.001, absolute risk = 3.0%). However, there were no significant associations in those aged 25-34 y (HR = 1.20, 95% CI 0.95-1.52, p = 0.125, absolute risk = 1.6%), in those aged 35-44 y (HR = 1.06, 95% CI 0.83-1.35, p = 0.666, absolute risk = 1.2%), or in those aged 45 y or older (HR = 1.07, 95% CI 0.84-1.35, p = 0.594, absolute risk = 0.3%). Associations in those aged 15 to 24 y were also found for violent crime arrests with preliminary investigations (HR = 1.28, 95% CI 1.16-1.41, p < 0.001), non-violent crime convictions (HR = 1.22, 95% CI 1.10 1.34, p < 0.001), non-violent crime arrests (HR = 1.13, 95% CI 1.07-1.20, p < 0.001), non-fatal injuries from accidents (HR = 1.29, 95% CI 1.22-1.36, p < 0.001), and emergency inpatient or outpatient treatment for alcohol intoxication or misuse (HR = 1.98, 95% CI 1.76-2.21, p < 0.001). With age and sex stratification, there was a significant association between SSRIs and violent crime convictions for males aged 15 to 24 y (HR = 1.40, 95% CI 1.13-1.73, p = 0.002) and females aged 15 to 24 y (HR = 1.75, 95% CI 1.08-2.84, p = 0.023). However, there were no significant associations in those aged 25 y or older. One important limitation is that we were unable to fully account for time-varying factors. CONCLUSIONS: The association between SSRIs and violent crime convictions and violent crime arrests varied by age group. The increased risk we found in young people needs validation in other studies. PMID- 26372358 TI - Genomic signatures for paclitaxel and gemcitabine resistance in breast cancer derived by machine learning. AB - Increasingly, the effectiveness of adjuvant chemotherapy agents for breast cancer has been related to changes in the genomic profile of tumors. We investigated correspondence between growth inhibitory concentrations of paclitaxel and gemcitabine (GI50) and gene copy number, mutation, and expression first in breast cancer cell lines and then in patients. Genes encoding direct targets of these drugs, metabolizing enzymes, transporters, and those previously associated with chemoresistance to paclitaxel (n = 31 genes) or gemcitabine (n = 18) were analyzed. A multi-factorial, principal component analysis (MFA) indicated expression was the strongest indicator of sensitivity for paclitaxel, and copy number and expression were informative for gemcitabine. The factors were combined using support vector machines (SVM). Expression of 15 genes (ABCC10, BCL2, BCL2L1, BIRC5, BMF, FGF2, FN1, MAP4, MAPT, NFKB2, SLCO1B3, TLR6, TMEM243, TWIST1, and CSAG2) predicted cell line sensitivity to paclitaxel with 82% accuracy. Copy number profiles of 3 genes (ABCC10, NT5C, TYMS) together with expression of 7 genes (ABCB1, ABCC10, CMPK1, DCTD, NME1, RRM1, RRM2B), predicted gemcitabine response with 85% accuracy. Expression and copy number studies of two independent sets of patients with known responses were then analyzed with these models. These included tumor blocks from 21 patients that were treated with both paclitaxel and gemcitabine, and 319 patients on paclitaxel and anthracycline therapy. A new paclitaxel SVM was derived from an 11-gene subset since data for 4 of the original genes was unavailable. The accuracy of this SVM was similar in cell lines and tumor blocks (70-71%). The gemcitabine SVM exhibited 62% prediction accuracy for the tumor blocks due to the presence of samples with poor nucleic acid integrity. Nevertheless, the paclitaxel SVM predicted sensitivity in 84% of patients with no or minimal residual disease. PMID- 26372361 TI - EDITORIAL: ENDORSEMENT OF THE EQUATOR NETWORK CONSENSUS REPORTING GUIDELINES. PMID- 26372362 TI - EARLY POSTOPERATIVE MAGNETIC RESONANCE IMAGING FINDINGS IN FIVE DOGS WITH CONFIRMED AND SUSPECTED BRAIN TUMORS. AB - Early postoperative neuroimaging has been performed in people for over 20 years to detect residual brain tumor tissue and surgical complications. The purpose of this retrospective study was to describe characteristics observed using early postoperative magnetic resonance imaging in a group of dogs undergoing craniotomy for brain tumor removal. Two independent observers came to a consensus opinion for presence/absence of the following MRI characteristics: residual tumor tissue; hemorrhage and ischemic lesions; abnormal enhancement (including the margins of the resection cavity, choroid plexus, meninges) and signal intensity changes on diffusion-weighted imaging. Five dogs were included in the study, having had preoperative and early postoperative MRI acquired within four days after surgery. The most commonly observed characteristics were abnormal meningeal enhancement, linear enhancement at margins of the resection cavity, hemorrhage, and a thin rim of hyperintensity surrounding the resection cavity on diffusion-weighted imaging. Residual tumor tissue was detected in one case of an enhancing tumor and in one case of a tumor containing areas of hemorrhage preoperatively. Residual tumor tissue was suspected but could not be confirmed when tumors were nonenhancing. Findings supported the use of early postoperative MRI as a method for detecting residual brain tumor tissue in dogs. PMID- 26372364 TI - Psychological effects of androgen-deprivation therapy on men with prostate cancer and their partners. AB - The clinical benefits of androgen-deprivation therapy (ADT) for men with prostate cancer (PC) have been well documented and include living free from the symptoms of metastases for longer periods and improved quality of life. However, ADT comes with a host of its own serious side effects. There is considerable evidence of the adverse cardiovascular, metabolic, and musculoskeletal effects of ADT. Far less has been written about the psychological effects of ADT. This review highlights several adverse psychological effects of ADT. The authors provide evidence for the effect of ADT on men's sexual function, their partner, and their sexual relationship. Evidence of increased emotional lability and depressed mood in men who receive ADT is also presented, and the risk of depression in the patient's partner is discussed. The evidence for adverse cognitive effects with ADT is still emerging but suggests that ADT is associated with impairment in multiple cognitive domains. Finally, the available literature is reviewed on interventions to mitigate the psychological effects of ADT. Across the array of adverse effects, physical exercise appears to have the greatest potential to address the psychological effects of ADT both in men who are receiving ADT and in their partners. PMID- 26372365 TI - Income Inequality or Performance Gap? A Multilevel Study of School Violence in 52 Countries. AB - PURPOSE: The purpose of the study was to examine the association between income inequality and school violence and between the performance inequality and school violence in two international samples. METHODS: The study used data from Trends in International Mathematics and Science Study 2011 and from the Central Intelligence Agency of United States which combined information about academic performance and students' victimization (physical and social) for 269,456 fourth grade students and 261,747 eighth-grade students, with gross domestic product and income inequality data in 52 countries. Ecological correlations tested associations between income inequality and victimization and between school performance inequality and victimization among countries. Multilevel ordinal regression and multilevel regression analyses tested the strength of these associations when controlling for socioeconomic and academic performance inequality at school level and family socioeconomic status and academic achievement at student level. RESULTS: Income inequality was associated with victimization rates in both fourth and eighth grade (r ~ .60). Performance inequality shows stronger association with victimization among eighth graders (r ~ .46) compared with fourth graders (r ~ .30). Multilevel analyses indicate that both an increase in the income inequality in the country and school corresponds with more frequent physical and social victimization. On the other hand, an increase in the performance inequality at the system level shows no consistent association to victimization. However, school performance inequality seems related to an increase in both types of victimizations. CONCLUSIONS: Our results contribute to the finding that income inequality is a determinant of school violence. This result holds regardless of the national performance inequality between students. PMID- 26372366 TI - Cannabinoid Hyperemesis Syndrome in a 17-Year-Old Adolescent. AB - Cannabis is the most widely used illicit drug in the world. In Canada, cannabis use has been decreasing among youth since 2008. However, it is still two times more prevalent than among adults. A distinct syndrome, characterized by recurrent vomiting associated with abdominal pain and compulsive bathing, has been increasingly recognized in chronic adult users. The cannabinoid hyperemesis syndrome (CHS) is still underdiagnosed among adults and even more among adolescents. The authors describe the case of a 17-year-old adolescent, who sought emergency care five times over a year for uncontrolled nausea, profuse vomiting, and weight loss. The patient's symptoms were ameliorated by repetitive hot showering and by avoiding cannabis use. Cannabinoid hyperemesis syndrome is a clinical diagnosis and should be consider in every case of cyclical vomiting. A review of the clinical aspects and the treatment is presented here. PMID- 26372367 TI - Licit and Illicit Substance Use by Adolescent E-Cigarette Users Compared with Conventional Cigarette Smokers, Dual Users, and Nonusers. AB - PURPOSE: Compare the lifetime prevalence of eight forms of substance use (alcohol, drunkenness, oral tobacco, snuff, sleeping pills/tranquilizers, sniffed glue, marijuana, and amphetamine) among adolescent e-cigarette (EC) users, conventional cigarette (CC) smokers, dual users, and nonusers. METHODS: We analyzed population-level school-survey data collected from 10th-grade students (aged 15-16 years) in February 2015 in Iceland (N = 3,477; response rate, 84.4%). RESULTS: Smoking rates were similar for both sexes. Around 17% had used ECs and almost 8% had used ECs and not combustible tobacco, 5%-6% had smoked CCs but not ECs, around 9% were dual users. EC-only users were significantly more likely than nonusers to have used the eight substances investigated in the study but were less likely to have used these substances than CC smokers and dual users. CONCLUSION: The four groups assessed in this study appear to form a sequential risk gradient to the use of other substances. PMID- 26372369 TI - Cross-Sectional Study of Young Adults Diagnosed With Juvenile Fibromyalgia: Social Support and Its Impact on Functioning and Mood. AB - PURPOSE: Juvenile-onset fibromyalgia (JFM) affects physical, social, and emotional functioning. Little is known about how social support and social interactions are impacted in the transition to young adulthood for patients diagnosed with JFM. METHODS: Young adults (Mage = 21.6) diagnosed with JFM during adolescence (N = 94) and matched healthy controls (N = 33) completed measures of social network size and diversity, perceived social support, physical functioning, and depressive symptoms as part of a cross-sectional survey study. RESULTS: No difference in social network diversity was found, although JFM patients reported fewer total people within their social networks. JFM patients reported poorer emotional and tangible support and fewer positive social interactions than healthy controls. After controlling for condition and pain intensity, the level of perceived social support was a significant predictor of physical functioning and depressive symptoms, whereas social network size also contributed uniquely to physical functioning. CONCLUSIONS: Given the developmental importance of social support in adolescence and young adulthood, interventions should include methods of improving social support into fibromyalgia management. PMID- 26372368 TI - Differential Impacts of an Intimate Partner Violence Prevention Program Based on Child Marriage Status in Rural Cote d'Ivoire. AB - PURPOSE: Little is known about whether effectiveness of intimate partner violence prevention programming varies for women who were married as child brides, given their additional social vulnerabilities. This subanalysis sought to assess treatment heterogeneity based on child marriage status for an intervention seeking to reduce intimate partner violence. METHODS: A randomized controlled trial assessing the incremental effectiveness of gender dialogue groups in addition to group savings on changing past-year intimate partner violence was conducted in Cote d'Ivoire (2010-2012). Stratified models were constructed based on child marriage status to assess for effect modification. Analysis was restricted to married women with data on age at marriage (n = 682). RESULTS: For child brides (N = 202), there were no statistically or marginally significant decreases in physical and/or sexual violence, physical violence, or sexual violence. The odds of reporting economic abuse in the past year were lower in the intervention arm for child brides relative to control group child brides (odds ratio [OR] = .33; 95% confidence interval [CI] = .13-.85; p = .02). For nonchild brides (N = 480), women were less likely to report physical and/or sexual violence (OR = .54; 95% CI = .28-1.04; p = .06), emotional violence (OR = .44; 95% CI = .25-.77; p = .004), and economic abuse (OR = .36; 95% CI = .20-.66; p = .001) in the combined intervention arm than their group savings-only counterparts. CONCLUSIONS: Findings suggest that intervention participants with a history of child marriage may have greater difficulty benefiting from interventions that seek to reduce intimate partner violence. PMID- 26372370 TI - The different metabolism of morusin in various species and its potent inhibition against UDP-glucuronosyltransferase (UGT) and cytochrome p450 (CYP450) enzymes. AB - 1. The aim of this study was to investigate the inhibitory effect of morusin on Glucuronosyltransferase (UGT) isoforms and cytochrome P450 enzymes (CYP450s). We also investigated the metabolism of morusin in human, rat, dog, monkey, and minipig liver microsomes. 2. 100 MUM of morusin exhibited strong inhibition on all UGTs and CYP450s. The half inhibition concentration (IC50) values for CYP3A4, CYP1A2, CYP2C9, CYP2E1, UGT1A6, UGT1A7, and UGT1A8 were 2.13, 1.27, 3.18, 9.28, 4.23, 0.98, and 3.00 MUM, and the inhibition kinetic parameters (Ki) were 1.34, 1.16, 2.98, 6.23, 4.09, 0.62, and 2.11 MUM, respectively. 3. Metabolism of morusin exhibited significant species differences. The quantities of M1 from minipig, monkey, dog, and rat were 7.8, 11.9, 2.0, and 6.3-fold of human levels. The Km values in HLMs, RLMs, MLMs, DLMs, and PLMs were 7.84, 22.77, 14.32, 9.13, and 22.83 MUM, and Vmax for these species were 0.09, 1.23, 1.43, 0.15, and 0.75 nmol/min/mg, respectively. CLint (intrinsic clearance) values (Vmax/Km) for morusin obeyed the following order: monkey > rat > minipig > dog > human. CLH (hepatic clearance) values for humans, dogs, and rats were calculated to be 8.28, 17.38, and 35.12 mL/min/kg body weight, respectively. 4. This study provided vital information to understand the inhibitory potential and metabolic behavior of morusin among various species. PMID- 26372371 TI - Palladium-Catalyzed Synthesis of 2-Aryl-2H-Benzotriazoles from Azoarenes and TMSN3. AB - Substrate-directed ortho C-H amination of azoarenes using TMSN3 as the source of nitrogen leading to the synthesis of 2-aryl-2H-benzotriazoles has been accomplished with the help of Pd/TBHP combinations. An intermolecular o-azidation (C-N bond formation) followed by an intramolecular N-N bond formation via nucleophilic attack of one of the azo nitrogen onto the o-azide nitrogen leads to cyclization with the expulsion of N2. PMID- 26372372 TI - Posterior Atrophy and Medial Temporal Atrophy Scores Are Associated with Different Symptoms in Patients with Alzheimer's Disease and Mild Cognitive Impairment. AB - BACKGROUND: Whether the occurrence of posterior atrophy (PA) and medial temporal lobe atrophy (MTA) was correlated with cognitive and non-cognitive symptoms in Alzheimer's disease (AD) and mild cognitive impairment (MCI) patients are unclear. METHODS: Patients with probable AD and MCI from a medical center outpatient clinic received attention, memory, language, executive function evaluation and Mini-Mental Status Examination (MMSE). The severity of dementia was rated by the Clinical Dementia Rating (CDR) Sum of Box (CDR-SB). The neuropsychiatric inventory (NPI) subscale of agitation/aggression and mood symptoms was also applied. Magnetic resonance imaging (MRI) was scored visually for the MTA, PA and white matter hyperintensity (WMH) scores. RESULTS: We recruited 129 AD and 31 MCI (mean age 78.8 years, 48% female) patients. MMSE scores, memory, language and executive function were all significantly decreased in individuals with AD than those with MCI (p < 0.01). MTA and PA scores reflected significant atrophy in AD compared to MCI; however, the WMH scores did not differ. The MTA scores were significantly correlated with the frontal, parieto-occipital and global WMH scores (p < 0.01) while the PA scores showed a correlation with the parieto-occipital and temporal WMH scores (p < 0.01). After adjusting for age, education, APOE4 gene and diagnostic group covariates, the MTA scores showed a significant association with MMSE and CDR-SB, while the right side PA scores were significantly associated with NPI-agitation/aggression subscales (p < 0.01). CONCLUSION: Regional atrophy is related to different symptoms in patients with AD or MCI. PA score is useful as a complementary measure for non-cognitive symptom. PMID- 26372373 TI - Synthetic Studies on Centromere-Associated Protein-E (CENP-E) Inhibitors: 2. Application of Electrostatic Potential Map (EPM) and Structure-Based Modeling to Imidazo[1,2-a]pyridine Derivatives as Anti-Tumor Agents. AB - To develop centromere-associated protein-E (CENP-E) inhibitors for use as anticancer therapeutics, we designed novel imidazo[1,2-a]pyridines, utilizing previously discovered 5-bromo derivative 1a. By site-directed mutagenesis analysis, we confirmed the ligand binding site. A docking model revealed the structurally important molecular features for effective interaction with CENP-E and could explain the superiority of the inhibitor (S)-isomer in CENP-E inhibition vs the (R)-isomer based on the ligand conformation in the L5 loop region. Additionally, electrostatic potential map (EPM) analysis was employed as a ligand-based approach to optimize functional groups on the imidazo[1,2 a]pyridine scaffold. These efforts led to the identification of the 5-methoxy imidazo[1,2-a]pyridine derivative (+)-(S)-12, which showed potent CENP-E inhibition (IC50: 3.6 nM), cellular phosphorylated histone H3 (p-HH3) elevation (EC50: 180 nM), and growth inhibition (GI50: 130 nM) in HeLa cells. Furthermore, (+)-(S)-12 demonstrated antitumor activity (T/C: 40%, at 75 mg/kg) in a human colorectal cancer Colo205 xenograft model in mice. PMID- 26372374 TI - An aquaporin PvTIP4;1 from Pteris vittata may mediate arsenite uptake. AB - The fern Pteris vittata is an arsenic hyperaccumulator. The genes involved in arsenite (As(III)) transport are not yet clear. Here, we describe the isolation and characterization of a new P. vittata aquaporin gene, PvTIP4;1, which may mediate As(III) uptake. PvTIP4;1 was identified from yeast functional complement cDNA library of P. vittata. Arsenic toxicity and accumulating activities of PvTIP4;1 were analyzed in Saccharomyces cerevisiae and Arabidopsis. Subcellular localization of PvTIP4;1-GFP fusion protein in P. vittata protoplast and callus was conducted. The tissue expression of PvTIP4;1 was investigated by quantitative real-time PCR. Site-directed mutagenesis of the PvTIP4;1 aromatic/arginine (Ar/R) domain was studied. Heterologous expression in yeast demonstrates that PvTIP4;1 was able to facilitate As(III) diffusion. Transgenic Arabidopsis showed that PvTIP4;1 increases arsenic accumulation and induces arsenic sensitivity. Images and FM4-64 staining suggest that PvTIP4;1 localizes to the plasma membrane in P. vittata cells. A tissue location study shows that PvTIP4;1 transcripts are mainly expressed in roots. Site-directed mutation in yeast further proved that the cysteine at the LE1 position of PvTIP4;1 Ar/R domain is a functional site. PvTIP4;1 is a new represented tonoplast intrinsic protein (TIP) aquaporin from P. vittata and the function and location results imply that PvTIP4;1 may be involved in As(III) uptake. PMID- 26372375 TI - Validation of the Penn Inventory of Scrupulosity (PIOS) in scrupulous and nonscrupulous patients: Revision of factor structure and psychometrics. AB - Scrupulosity, or obsessive-compulsive symptoms related to religiosity or religion, is a common presentation of obsessive compulsive disorder (OCD), and it is important to elucidate its phenomenology and measurement. Today, the most widespread questionnaire for the assessment of scrupulosity is the Penn Inventory of Scrupulosity (PIOS). The current study examines the psychometric properties of the PIOS in outpatient, treatment-seeking patients. Results of a confirmatory factor analysis suggested an unsatisfactory fit for previously suggested factor structures. A follow-up exploratory factor analysis suggested that a bifactor model was the most suitable solution. In addition, the scores of the PIOS and its revised subscales were found to have moderate-good concurrent validity; however, its scores discriminated poorly between patients with scrupulous obsessions and patients with OCD and other repugnant obsessions. Group differences and receiver operating characteristics (ROC) analyses both indicated that the PIOS is more suitable in discriminating scrupulous obsessions in Christian patients but not in other religious groups (i.e., Jews, nonreligious patients). Additional analyses revealed that the co-occurrence of scrupulous and other repugnant obsessions is also moderated by religious affiliation. These results raise questions in terms of grouping scrupulosity with other repugnant obsessions and suggest for the need of culturally sensitive instruments of scrupulosity. (PsycINFO Database Record PMID- 26372376 TI - Silver nanoparticles impede phorbol myristate acetate-induced monocyte-macrophage differentiation and autophagy. AB - Monocytes/macrophages are important constituents of the innate immune system. Monocyte-macrophage differentiation is not only crucial for innate immune responses, but is also related to some cardiovascular diseases. Silver nanoparticles (AgNPs) are one of the most widely used nanomaterials because of their broad-spectrum antimicrobial properties. However, the effect of AgNPs on the functions of blood monocytes is scarcely reported. Here, we report the impedance effect of AgNPs on THP-1 monocyte differentiation, and that this effect was mediated by autophagy blockade and lysosomal impairment. Firstly, AgNPs inhibit phorbol 12-myristate 13-acetate (PMA)-induced monocyte differentiation by down-regulating both expression of surface marker CD11b and response to lipopolysaccharide (LPS) stimulation. Secondly, autophagy is activated during PMA induced THP-1 monocyte differentiation, and the autophagy inhibitor chloroquine (CQ) can inhibit this process. Thirdly, AgNPs block the degradation of the autophagy substrate p62 and induce autophagosome accumulation, which demonstrates the blockade of autophagic flux. Fourthly, lysosomal impairments including alkalization and decrease of lysosomal membrane stability were observed in AgNP treated THP-1 cells. In conclusion, we demonstrate that the impedance of monocyte macrophage differentiation by AgNPs is mediated by autophagy blockade and lysosomal dysfunction. Our results suggest that crosstalk exists in different biological effects induced by AgNPs. PMID- 26372377 TI - The Authors Respond. PMID- 26372378 TI - Selection Bias Due to Parity-conditioning in Studies of Time Trends in Fertility. PMID- 26372379 TI - Maternal and neonatal outcomes in women with twin pregnancies with excessive gestational weight gain. AB - OBJECTIVE: To determine if an excessive rate of gestational weight gain (GWG) in twin pregnancies is associated with adverse obstetric outcomes. METHODS: Retrospective cohort study of twin pregnancies delivered at the University of California, San Diego 2001-2014. Women were included if they had adequate or excessive rates of GWG as determined by Institute of Medicine guidelines. Demographic and outcome variables were collected by chart review. RESULTS: Four hundred and eighty-nine twin pregnancies met inclusion criteria. Of which, 40.5% had adequate rates of GWG and 41.5% had excessive rates of GWG. The rates of preterm birth and gestational diabetes were similar between the two groups. Gestational hypertension and preeclampsia were more common in women with excessive GWG (37.9% versus 19.7%; p < 0.01). This finding persisted in multivariate analysis. The mean birth weight percentiles were higher in the excessive GWG group and these women were also less likely to have an infant with a birth weight <10th percentile (21.4% versus 35.9%, p < 0.01). CONCLUSIONS: Excessive GWG is associated with a higher risk for gestational hypertension and preeclampsia, but no other adverse perinatal outcomes. Infants born to mothers with excessive GWG are less likely to be small for gestational age than those born to women with adequate GWG. PMID- 26372381 TI - Persistent subclinical immune defects in HIV-1-infected children treated with antiretroviral therapy. AB - OBJECTIVES: With the introduction of combined antiretroviral therapy (cART), HIV infected children can reach adulthood with minimal clinical complications. However, long-term HIV and cART in adults are associated with immunosenescence and end-organ damage. Long-term consequences of HIV and cART in children are currently unknown. DESIGN AND METHOD: We studied 69 HIV-infected children and adolescents under cART (0-23 years) for the occurrence of subclinical immunological aberrations in blood B and T cells, using detailed flow cytometric immunophenotyping and molecular analyses. RESULTS: Children with undetectable plasma HIV viral loads for more than 1 year showed near-normal to normal CD4 T cell numbers and near-normal numbers of most class-switched memory B cells. Furthermore, expansions of aberrant CD21 B cells contracted in patients with virus suppression. In contrast, CD8 effector T cells were increased, and CD4 memory T cells, Vgamma9Vdelta2 T cells and CD27IgA memory B cells were decreased and did not normalize under ART. Moreover, Vgamma9Vdelta2 T cells showed defects in their T-cell receptor repertoire selection. CONCLUSION: Our results show the effectiveness of current cART to enable the build-up of phenotypically diverse B cell and T-cell memory in HIV-infected children. However, several subclinical immune abnormalities were detected, which were partially caused by defective immune maturation. These persistent abnormalities were most severe in adolescents and therefore warrant long-term follow-up of HIV-infected children. Early identification of such immune defects might provide targets for monitoring future treatment optimization. PMID- 26372380 TI - Impact of TRIM5alpha in vivo. AB - HIV type 1 (HIV-1) has a very narrow host range that is limited to humans and chimpanzees. HIV-1 cannot replicate well in Old World monkey cells such as rhesus and cynomolgus monkeys. Tripartite motif (TRIM)5alpha is a key molecule that confers potent resistance against HIV-1 infection and is composed of really interesting new gene, B-box2, coiled-coil and PRYSPRY domains. Interaction between TRIM5alpha PRYSPRY domains and HIV-1 capsid core triggers the anti-HIV-1 activity of TRIM5alpha. Analysis of natural HIV variants and extensive mutational experiments has revealed the presence of critical amino acid residues in both the PRYSPRY domain and HIV capsid for potent HIV suppression by TRIM5alpha. Genetic manipulation of the human TRIM5 gene could establish human cells totally resistant to HIV-1, which may lead to a cure for HIV-1 infection in the future. PMID- 26372382 TI - Lysis of HIV-1-infected autologous CD4+ primary T cells by interferon-alpha activated NK cells requires NKp46 and NKG2D. AB - OBJECTIVE: Autologous HIV-1-infected CD4 primary T cells (aHIVCD4) have been shown to be largely resistant to natural killer (NK)-cell-mediated lysis because of viral strategies of immune evasion. We have previously shown that a preactivation of NK cells with plasmacytoid dendritic cells can significantly augment lysis of aHIVCD4 through a mechanism dependent on interferon-alpha (IFN alpha). DESIGN: The goal of the present study is to identify the specific NK activating receptors involved in NK lysis of aHIVCD4 following IFN-alpha activation. METHODS: Peripheral blood mononuclear cells (PBMC) were incubated with aHIVCD4 to induce the secretion of endogenous levels of IFN-alpha and drive NK activation. We then utilized a standard chromium lysis assay to assess the degree of IFN-alpha-activated lysis of aHIVCD4 in the presence or absence of masking antibodies to a panel of NK-activating receptors and co-receptors. RESULTS: Direct recognition of HIV-1-infected, but not uninfected, autologous CD4 primary T cells by PBMC induced the secretion IFN-alpha (median 2280 pg/ml, P < 0.001, n = 9) that, in turn, activated NK cells (P < 0.001, n = 12) and significantly increased their cytolytic potential against aHIVCD4 (P < 0.01, n = 12). The masking of NKp46 (P < 0.01, n = 8) and NKG2D (P < 0.05, n = 8), but not 2B4, NTBA, NKp30 or NKp44, significantly reduced IFN-alpha-activated lysis of aHIVCD4. CONCLUSIONS: Taken together, these results demonstrate that endogenous levels of IFN-alpha secreted by plasmacytoid dendritic cells induce NK cells to lyse aHIVCD4 via the engagement of NKp46 and NKG2D. PMID- 26372383 TI - A prospective, randomized clinical trial of antiretroviral therapies on carotid wall thickness. AB - OBJECTIVE: This article compares the effects of initiating three contemporary antiretroviral therapy (ART) regimens on progression of carotid artery intima media thickness (IMT) over 3 years. DESIGN: Randomized clinical trial. SETTING: Multicenter (26 institutions). PATIENTS: ART-naive HIV-infected individuals (n = 328) without known cardiovascular disease or diabetes mellitus. INTERVENTION: Random assignment to tenofovir/emtricitabine along with atazanavir/ritonavir (ATV/r), darunavir/ritonavir (DRV/r), or raltegravir (RAL). MAIN OUTCOME MEASURES: Right-sided carotid IMT was evaluated by B-mode ultrasonography before ART initiation, and then after 48, 96, and 144 weeks. Comparisons of yearly rates of change in carotid IMT used mixed-effects linear regression models that permitted not only evaluation of the effects of ART on carotid IMT progression but also how ART-associated changes in traditional risk factors, bilirubin, and markers of HIV infection were associated carotid IMT progression. RESULTS: HIV-1 RNA suppression rates were high in all arms (>85%) over 144 weeks. Modest increases in triglycerides and non-high-density lipoprotein cholesterol levels were observed in the protease inhibitor-containing arms compared with decreases with RAL. In contrast, carotid IMT progressed more slowly on ATV/r [8.2, 95% confidence interval (5.6, 10.8) MUm/year] than DRV/r [12.9 (10.3, 15.5) MUm/year, P = 0.013]; changes with RAL were intermediate [10.7 (9.2, 12.2) MUm/year, P = 0.15 vs. ATV/r; P = 0.31 vs. DRV/r]. Bilirubin and non-high-density lipoprotein cholesterol levels appeared to influence carotid IMT progression rates. CONCLUSION: In ART-naive HIV-infected individuals at low cardiovascular disease risk, carotid IMT progressed more slowly in participants initiating ATV/r than those initiating DRV/r, with intermediate changes associated with RAL. This effect may be due, in part, to hyperbilirubinemia. PMID- 26372385 TI - White matter micro-structural changes in ART-naive and ART-treated children and adolescents infected with HIV in South Africa. AB - OBJECTIVE: To describe the effect of HIV on white matter integrity and neurocognitive function in children vertically infected with HIV, compared to a HIV-negative healthy control group. DESIGN: Cross-sectional. METHODS: We compared 75 HIV-infected children aged 6-16 years, including children on antiretroviral therapy (ART) and those who were ART-naive, with 30 controls on diffusion tensor imaging and a neuropsychological battery sensitive to fronto-striatal pathology. In a secondary analysis, we compared 'slow progressor' ART-naive children, children on ART without a diagnosis of encephalopathy and children on ART with HIV encephalopathy. RESULTS: Compared to controls (n = 30), HIV-infected children (n = 75) displayed decreased fractional anisotropy and axial diffusion, and increased mean diffusivity and radial diffusion, indicating damaged neuronal microstructure. HIV-infected children performed poorly on the neuropsychological battery (P = <0.001). Within the HIV-infected group, children with HIV encephalopathy (n = 14) had poor white matter integrity when compared to ART treated children without encephalopathy (n = 41), and there was significant myelin loss in ART-naive children (n = 20), compared with ART-treated children. ART-treated children had significant axonal damage in the corpus callosum (P = 0.009). CONCLUSION: Children infected with HIV, irrespective of treatment status, displayed significantly poorer white matter integrity and impaired cognition compared to HIV-negative controls. Our findings suggest that despite immune recovery in children on ART, they remain at risk for developing central nervous system disease, and that initiation of ART as early as possible may reduce the risk of developing white matter damage in ART-naive slow progressors. PMID- 26372384 TI - Effects of renal tubular dysfunction on bone in tenofovir-exposed HIV-positive patients. AB - OBJECTIVES: Tenofovir disoproxil fumarate (TDF) may cause renal tubular dysfunction (RTD) and reduce bone mineral density (BMD). We examined the relationship between RTD and BMD in TDF-exposed HIV-positive men. DESIGN AND METHODS: We analysed urinary retinol-binding protein/creatinine ratio (RBPCR) and fractional excretion of phosphate (FEPO4) to quantify RTD in a cross-sectional sample of randomly selected HIV-positive men at a single tertiary outpatient clinic. BMD at the lumbar spine and hip was measured by dual-energy X-ray absorptiometry. Multivariate logistic regression was used to analyse factors associated with RTD, and linear regression to examine the relationship between RTD and BMD. RESULTS: Of 293 men (mean age 48 years, 94% White ethnicity, median TDF exposure 2.1 years), 22.5% had RBPCR-defined RTD and 12.3% had FEPO4-defined RTD. We observed a negative correlation between RBPCR and BMD at the spine (beta 0.2, P = 0.002) and hip (total: beta -0.1, P = 0.02; femoral neck: beta -0.1, P = 0.02), but not between FePO4 and BMD. In multivariable analyses, RTD defined by more than five-fold elevations in RBPCR was associated with significantly lower BMD of the spine. CONCLUSION: In HIV-positive patients receiving TDF-containing antiretroviral therapy, RTD was associated with lower BMD of the spine in HIV positive men. RBPCR quantification may identify patients at increased risk of TDF associated BMD loss. PMID- 26372386 TI - The impact of vaccination on the breadth and magnitude of the antibody response to influenza A viruses in HIV-infected individuals. AB - OBJECTIVE: HIV-positive individuals have lower antibody titers to influenza viruses than HIV-negative individuals, and the benefits of the annual vaccinations are controversially discussed. Also, there is no information about the breadth of the antibody response in HIV-infected individuals. DESIGN: The binding and neutralizing antibody titers to various human and nonhuman influenza A virus strain were determined in sera from 146 HIV-infected volunteers: They were compared with those found in 305 randomly selected HIV-negative donors, and put in relation to HIV-specific parameters. Univariable and multivariable regression was used to identify HIV-specific parameters associated with the measured binding and neutralizing activity. METHODS: Enzyme-linked immunosorbent assays and in-vitro neutralization assays were used to determine the binding and neutralizing antibodiy titers to homo and heterosubtypic influenza A subtypes. RESULTS: We found that both homo and heterosubtypic antibody titers are lower in HIV-positive individuals. Vaccination promoted higher binding and neutralizing antibody titers to human but not to nonhuman isolates. HIV-induced immune damage (high viral load, low CD4 T-cell counts, and long untreated disease progression) is associated with impaired homosubtypic responses, but can have beneficial effects on the development of heterosubtypic antibodies, and an improved ratio of binding to neutralizing antibody titers to homosubtypic isolates. CONCLUSIONS: Our results indicate that repetitive vaccinations in HIV-positive individuals enhance antibody titers to human isolates. Interestingly, development of antibody titers to conserved heterosubtypic epitopes paradoxically appeared to profit from HIV-induced immune damage, as did the ratio of binding to neutralizing antibodies. PMID- 26372387 TI - Week 48 efficacy and central nervous system analysis of darunavir/ritonavir monotherapy versus darunavir/ritonavir with two nucleoside analogues. AB - BACKGROUND: In previous studies in virologically suppressed patients, protease inhibitor monotherapy has shown trends for more low-level elevations in HIV-1 RNA compared with triple therapy, but no increase in the risk of drug resistance. METHODS: A total of 273 patients with HIV-1 RNA less than 50 copies/ml on first line antiretrovirals switched to darunavir/ritonavir (DRV/r) 800/100 mg once daily, either as monotherapy (n = 137) or as triple therapy with two nucleoside analogues (n = 136). Treatment failure was defined as HIV-1 RNA levels 50 copies/ml or above, or discontinuation of study treatment by week 48 (FDA Snapshot algorithm). RESULTS: Patients were 83% male and 88% white, with mean age 42 years. In the primary efficacy analysis, HIV-1 RNA less than 50 copies/ml by week 48 [intention-to-treat (ITT)] was 118 of 137 (86%) in the DRV/r monotherapy arm versus 129 of 136 (95%) in the triple therapy arm (difference = -8.7%, 95% confidence interval -15.50, -1.80). In a post-hoc analysis, for patients with nadir CD4 cell count 200 cells/MUl or above, rates of HIV-1 RNA suppression were 91 of 96 (95%) in the DRV/r monotherapy arm and 100 of 106 (94%) in the triple therapy arm. There was no difference in neurocognitive function or the risk of neuropsychiatric adverse events between DRV/r monotherapy and triple therapy. Two patients in the monotherapy arm with CD4 nadir less than 200 cells/MUl developed viraemia in both cerebrospinal fluid (CSF) and plasma, with one symptomatic case. CONCLUSIONS: In this study for patients with HIV-1 RNA less than 50 copies/ml at baseline, switching to DRV/r monotherapy showed lower efficacy versus triple therapy at week 48 in the primary ITT switch equals failure analysis, with two cases of viraemia in the CSF in the protease inhibitor monotherapy arm. PMID- 26372388 TI - Regression of liver stiffness after sustained hepatitis C virus (HCV) virological responses among HIV/HCV-coinfected patients. AB - OBJECTIVE: We assessed the impact of a sustained virological response (SVR) on liver stiffness among HIV/hepatitis C virus (HCV)-coinfected patients enrolled in the ANRS CO13 HEPAVIH cohort. METHODS: We studied HIV/HCV-coinfected patients who received at least one dose of any anti-HCV treatment and who had documented SVR status, a pretreatment FibroScan value of at least 7.1 kPa, and at least one posttreatment FibroScan value. The time required to achieve at least a 30% decrease in liver stiffness was analyzed by constructing Kaplan-Meier curves and using Cox proportional hazards models. RESULTS: Among 98 patients treated for HCV infection with either pegylated interferon along with ribavirin (n = 89) or protease inhibitor-based triple therapy (n = 9), 53 patients (54%) had an SVR. Median follow-up was 44.6 (interquartile range: 28.8-58.9) months. The probability of achieving a 30% decrease in FibroScan values was 51% [95% confidence interval (CI): 39-66] in patients with an SVR and 21% in nonresponders (95% CI: 11-36) at 1 year, and 74% (61-86) and 28% (17-44) at 2 years, respectively. In the subgroup of 35 cirrhotic patients (pretreatment liver stiffness >=12.5 kPa), 14 of 18 patients with an SVR and three of 17 nonresponders had a fibrosis score below 12.5 kPa at the last follow-up examination. Multivariable analysis showed that SVR was independently associated with a >=30% reduction in liver stiffness, both in the overall study group (hazard ratio: 5.77; 95% CI: 2.00-16.62; P = 0.0012) and in cirrhotic patients (hazard ratio: 8.21; 95% CI: 2.15-31.34; P = 0.0021). Robustness analyses using FIB4 values showed similar results. CONCLUSION: SVR is significantly associated with improvement in liver stiffness in HIV/HCV-coinfected patients, including those with cirrhosis. PMID- 26372389 TI - Renal tubular disease in the era of combination antiretroviral therapy. AB - OBJECTIVES: To describe the spectrum of renal tubular disease (RTD) in HIV positive patients and its association with exposure to antiretroviral therapy (ART). DESIGN: Review of 265 consecutive renal biopsies from HIV-positive patients attending eight clinics in the United Kingdom between 2000 and 2012. METHODS: We described the clinical characteristics of patients with RTD and compared current/recent exposure (at the time of, or up to 3 months prior to the date of biopsy) to potentially nephrotoxic ART [tenofovir (TDF), atazanavir (ATV), indinavir (IDV) and lopinavir/ritonavir (LPV/r)]. We also analysed the incidence of RTD in the UK CHIC cohort. Kruskall-Wallis, analysis of variance and Fisher's exact tests were used to evaluate between-group differences. RESULTS: Of the 60 RTD cases, 54 (90%) were included in the analyses. RTD comprised of three distinct patterns: acute tubular injury (ATI, n = 22), tubulo-interstitial nephritis (TIN, n = 20) and interstitial fibrosis and tubular atrophy (IFTA, n = 12). Compared with TIN and IFTA, ATI cases were less likely to be of black ethnicity (10 vs. 42-55%; P = 0.006), more likely to be on ART (100 vs. 55-68%; P = 0.001), with HIV-RNA below 200 copies/ml (100 vs. 54-58%; P < 0.001), and more likely to have current/recent exposure to TDF (P < 0.001). We did not find evidence for an association between exposure to TDF, ATV/r or LPV/r and either TIN or IFTA. CONCLUSION: RTD was present in approximately 20% of renal biopsies and comprised three distinct injury patterns with considerable clinical overlap. ATI was associated with TDF exposure, although the overall incidence of biopsy defined ATI was low. PMID- 26372390 TI - Do HIV prevalence trends in antenatal clinic surveillance represent trends in the general population in the antiretroviral therapy era? The case of Manicaland, East Zimbabwe. AB - OBJECTIVE: National estimates of HIV trends in generalized epidemics rely on HIV prevalence data from antenatal clinic (ANC) surveillance. We investigate whether HIV prevalence trends in ANC data reflect trends in men and women in the general population during the scale-up of antiretroviral therapy (ART) in Manicaland, Zimbabwe. METHODS: Trends in HIV prevalence in local ANC attendees and adults aged 15-49 years in towns, agricultural estates, and villages were compared using five rounds of parallel ANC (N = 1200) and general-population surveys (N = 10 000) and multivariable log-linear regression. Changes in the age pattern of HIV prevalence and the age distribution of ANC attendees were compared with those in the general population. Age-specific pregnancy prevalence rates were compared by HIV infection and ART status. RESULTS: Cumulatively, from 1998-2000 to 2009-2011, HIV prevalence fell by 60.0% (95% confidence interval, 51.1-67.3%) in ANC surveillance data and by 34.3% (30.8-37.7%) in the general population. Most of the difference arose following the introduction of ART (2006-2011). The estates and villages reflected this overall pattern but HIV prevalence in the towns was lower at local ANCs than in the general population, largely because of attendance by pregnant women from outlying (lower prevalence) areas. The ageing of people living with HIV in the general population (52.4% aged >35 years, 2009-2011) was under-represented in the ANC data (12.6%) because of lower fertility in older and HIV-infected women. CONCLUSION: After the introduction of ART in Manicaland, HIV prevalence declined more steeply in ANC surveillance data than in the general population. Models used for HIV estimates must reflect this change in bias. PMID- 26372392 TI - Phylodynamics of major HIV-1 subtype B pandemic clades circulating in Latin America. AB - OBJECTIVE: To obtain a comprehensive description of the evolutionary and demographic history of major HIV-1 subtype B pandemic (BPANDEMIC) clades circulating in Latin America. DESIGN: A total of 6789 HIV-1 subtype B pol sequences collected from seven different Latin American countries between 1990 and 2011 were combined with BPANDEMIC reference sequences (n = 500) from the United States and France. METHODS: Major BPANDEMIC clades were identified by maximum likelihood phylogenetic analysis with sequential pruning of ambiguously positioned taxa. Time scale and demographic reconstructions were performed using a Bayesian coalescent-based method. RESULTS: We identified 12 major BPANDEMIC monophyletic lineages mainly composed by Latin American sequences and that together comprise 36% of all subtype B sequences from the region here included. Four clades belong to two major regional lineages that comprise sequences from at least two neighboring countries, whereas the other eight clades were country specific. The median age of major Latin American BPANDEMIC clades encompass a period of two decades (1968-1988), although most of them probably arose before the early 1980s. All major clades seem to have experienced an initial period of exponential growth, with median epidemic growth rates that range from 0.50 yearto 0.94 year, followed by a recent decline in growth rate. CONCLUSION: About one third of HIV-1 subtype B infections in Latin America originated from the spread of a few BPANDEMIC founder strains probably introduced in the region since the late 1960s. Despite their initial successful dissemination, all major BPANDEMIC clades showed signs of subsequent epidemic stabilization. PMID- 26372391 TI - Potential impact on HIV incidence of higher HIV testing rates and earlier antiretroviral therapy initiation in MSM. AB - BACKGROUND: Increased rates of testing, with early antiretroviral therapy (ART) initiation, represent a key potential HIV-prevention approach. Currently, in MSM in the United Kingdom, it is estimated that 36% are diagnosed by 1 year from infection, and the ART initiation threshold is at CD4 cell count 350/MUl. We investigated what would be required to reduce HIV incidence in MSM to below 1 per 1000 person-years (i.e. <535 new infections per year) by 2030, and whether this is likely to be cost-effective. METHODS: A dynamic, individual-based simulation model was calibrated to multiple data sources on HIV in MSM in the United Kingdom. Outcomes were projected according to future alternative HIV testing and ART initiation scenarios to 2030, considering also potential changes in levels of condomless sex. RESULTS: For ART use to result in an incidence of close to 1/1000 person-years requires the proportion of all HIV-positive MSM with viral suppression to increase from below 60% currently to 90%, assuming no rise in levels of condomless sex. Substantial increases in HIV testing, such that over 90% of men are diagnosed within a year of infection, would increase the proportion of HIV-positive men with viral suppression to 80%, and it would be 90%, if ART is initiated at diagnosis. The scenarios required for such a policy to be cost-effective are presented. CONCLUSION: This analysis provides targets for the proportion of all HIV-positive MSM with viral suppression required to achieve substantial reductions in HIV incidence. PMID- 26372393 TI - Impact of the Ebola epidemic on general and HIV care in Macenta, Forest Guinea, 2014. AB - OBJECTIVE: The current Ebola epidemic massively affected the Macenta district in Forest Guinea. We aimed at investigating its impact on general and HIV care at the only HIV care facility in the district. DESIGN: Prospective observational single-facility study. METHODS: Routinely collected data on use of general hospital services and HIV care were linked to Ebola surveillance data published by the Guinea Ministry of Health. In addition, we compared retention among HIV infected patients enrolled into care in the first semesters of 2013 and 2014. RESULTS: Throughout 2014, service offer was continuous and unaltered at the facility. During the main epidemic period (August-December 2014), compared with the same period of 2013, there were important reductions in attendance at the primary care outpatient clinic (-40%), in HIV tests done (-46%), in new diagnoses of tuberculosis (-53%) and in patients enrolled into HIV care (-47%). There was a smaller reduction in attendance at the HIV follow-up clinic (-11%). Kaplan-Meier estimates of retention were similar among the patients enrolled into care in 2014 and 2013. In a multivariable Cox regression analysis, the year of enrolment was not associated with attrition (hazard ratio 1.02; 95% confidence interval: 0.72 1.43). CONCLUSION: The Ebola epidemic resulted in an important decrease in utilization of the facility despite unaltered service offer. Effects on care of HIV-positive patients enrolled prior to the epidemic were limited. HIV care in such circumstances is challenging, but not impossible. PMID- 26372394 TI - IFNL4 rs368234815 polymorphism is associated with innate resistance to HIV-1 infection. AB - The interferon (IFN)L4 polymorphism rs368234815 is associated with hepatitis C virus (HCV) spontaneous clearance and response to IFN-based treatments. The role of this polymorphism in HIV-1 infection is controversial. We investigated whether genetic variation at IFNL4 is associated to HIV-1 acquisition. The HCV protective allele TT was associated with decreased likelihood of HIV-1 infection in male intravenous drug users [odds ratio (OR): 0.3; P = 0.006], and this association was not modified by the genotype of CCR5. These results suggest that genetic susceptibility to HCV and HIV-1 infection shares common molecular pathways. PMID- 26372395 TI - Increasing glutathione concentrations with cysteine and glycine supplementation lowers inflammation in HIV patients. PMID- 26372396 TI - Case report: an 11-year-old girl presenting with asymptomatic retinal vasculitis leading to diagnosis of HIV-1 infection. PMID- 26372397 TI - Antihepatitis C virus treatments for HIV-hepatitis C virus coinfected cirrhotic patients: a need to look beyond the sustained viral response. PMID- 26372399 TI - Twelve tips for getting your manuscript published. AB - The author shares twelve practical tips on how to navigate the process of getting a manuscript published. These tips, which apply to all fields of academic writing, advise that during the initial preparation phase authors should: (1) plan early to get it out the door; (2) address authorship and writing group expectations up front; (3) maintain control of the writing; (4) ensure complete reporting; (5) use electronic reference management software; (6) polish carefully before they submit; (7) select the right journal; and (8) follow journal instructions precisely. Rejection after the first submission is likely, and when this occurs authors should (9) get it back out the door quickly, but first (10) take seriously all reviewer and editor suggestions. Finally, when the invitation comes to revise and resubmit, authors should (11) respond carefully to every reviewer suggestion, even if they disagree, and (12) get input from others as they revise. The author also shares detailed suggestions on the creation of effective tables and figures, and on how to respond to reviewer critiques. PMID- 26372398 TI - A Mosaic Expression of a Hb J-Amiens (HBB: c.54G > T; p.Lys18Asn) and its Interference with Hb A1c Analysis. AB - We report the case of a 56-year-old Caucasian woman in whom hemoglobinopathy screening was triggered following an aberrant Hb A1c analysis. Preliminary diagnosis of the hemoglobin (Hb) variant was obtained through cation exchange high performance liquid chromatography (HPLC) and gel electrophoresis. DNA analysis confirmed the presence of Hb J-Amiens [beta17(A14)Lys->Asn; HBB: c.[54G > C or 54G > T)]. However, an unbalanced ratio between wild type and mutant signal after direct sequencing and a lower than expected percentage of this Hb variant led to the suggestion of a mosaic expression. Furthermore, different methods [capillary zone electrophoresis (CZE), cation exchange HPLC and boronate affinity] were tested to study the possible interference of this variant with Hb A1c measurements. These investigations showed a clinically relevant difference between the methods tested. Hb A1c analysis may lead to the discovery of new Hb variants or mosaicism for previously described Hb variants. This may have genetic consequences for the offspring of carriers and brings about the question of partner testing. PMID- 26372400 TI - Surgery versus endoscopic cauterization in patients with third or fourth branchial pouch sinuses: A systematic review. AB - OBJECTIVES: To systematically review the current literature on treatment of third and fourth branchial pouch sinuses with endoscopic cauterization, including chemocauterization and electrocauterization, in comparison to surgical treatment. DATA SOURCES: PubMed, Embase, and the Cochrane Library. REVIEW METHODS: We conducted a systematic search. Studies reporting original study data were included. After assessing the directness of evidence and risk of bias, studies with a low directness of evidence or a high risk of bias were excluded from analysis. Cumulative success rates after initial and recurrent treatments were calculated for both methods. A meta-analysis was conducted comparing the success rate of electrocauterization and surgery. RESULTS: A total of 2,263 articles were retrieved, of which seven retrospective and one prospective article were eligible for analysis. The cumulative success rate after primary treatment with cauterization ranged from 66.7% to 100%, and ranged from 77.8% to 100% after a second cauterization. The cumulative success rate after the first surgical treatment ranged from 50% to 100% and was 100% after the second surgical attempt. Meta-analysis on electrocauterization showed a nonsignificant risk ratio of 1.35 (95% confidence interval: 0.78-2.33). CONCLUSIONS: The effectiveness of cauterization in preventing recurrence seems to be comparable to surgical treatment. However, we suggest endoscopic cauterization as the treatment of choice for third and fourth branchial pouch sinuses because of the lower morbidity rate. PMID- 26372401 TI - EFFECTS OF HOMEWORK COMPLIANCE ON COGNITIVE-BEHAVIORAL THERAPY WITH D-CYCLOSERINE AUGMENTATION FOR CHILDREN WITH OBSESSIVE COMPULSIVE DISORDER. AB - BACKGROUND: The present study examined the effects of homework compliance on outcome from cognitive behavioral therapy (CBT) for children with obsessive compulsive disorder (OCD) and the extent to which these effects differ as a function of augmentation of CBT with D-cycloserine (DCS). METHODS: Twenty-seven youth with OCD were randomized to either 50 mg DCS or placebo (PBO) administered immediately after each of 10 CBT sessions, primarily consisting of exposure and ritual prevention (ERP). Independent evaluators assessed OCD severity using the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) at the start of each session. Compliance with between-session ERP assignments was also assessed at the start of each session using the Patient ERP Adherence Scale (PEAS). RESULTS: Greater homework compliance between the previous session and the current session was related to lower CY-BOCS at the current session. However, the relation between homework compliance and CY-BOCS varied by treatment condition. Higher homework compliance was related to lower CY-BOCS for participants in the DCS condition, but not for participants in the PBO condition. Furthermore, participants receiving DCS were estimated to have significantly lower CY-BOCS than those given PBO among those with the highest levels of homework compliance. CONCLUSIONS: DCS may more effectively facilitate the effects of CBT for youth with OCD when patients are compliant with prescribed homework. Theoretical and clinical implications are discussed. PMID- 26372402 TI - Concentration-dependent effects of alendronate and pamidronate functionalized gold nanoparticles on osteoclast and osteoblast viability. AB - Severe osteoporotic diseases, such as Paget's disease, Osteogenesis Imperfecta, and Legg Calve Perthes disease, lack treatments that address the pathobiology of the diseases, as well as, long-term and prospective studies. Bisphosphonates, which are known to dramatically hinder the viability of osteoclast cells, along with gold nanoparticles (GNP) are a potential theranostic for osteoporotic diseases. We evaluated GNP functionalized with two different bisphosphonates, namely, alendronate and pamidronate. RANKL differentiated murine pre-osteoclasts (Raw 264.7) and murine osteoblasts (7F2) were treated with varying concentrations ranging from 0.1-5 uM of free and GNP bound bisphosphonates. GNPs with an average size of ~15 nm were functionalized with alendronate and pamidronate through surface modification by self-assembly. MTT viability assay results show no changes in viability of the osteoclasts when treated with free bisphosphonates in the range of 1-5 uM, but significant decrease on treatment with functionalized GNP at concentrations above the range of 0.1-1 uM depending on the bisphosphonate. Osteoblast cell viability is maintained at all but the highest concentrations used. Qualitative and quantitative characterization by Western Blot for RANKL expression in the osteoblast cell line shows that expression is largely maintained. These results provide a basis for methods that use bisphosphonate functionalized GNP in the treatment of osteoporotic bone diseases. (c) 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 21-29, 2017. PMID- 26372403 TI - Atmospheric chemistry of (CF3)2C=CH2: OH radicals, Cl atoms and O3 rate coefficients, oxidation end-products and IR spectra. AB - The rate coefficients for the gas phase reactions of OH radicals, k1, Cl atoms, k2, and O3, k3, with 3,3,3-trifluoro-2(trifluoromethyl)-1-propene ((CF3)2C=CH2, hexafluoroisobutylene, HFIB) were determined at room temperature and atmospheric pressure employing the relative rate method and using two atmospheric simulation chambers and a static photochemical reactor. OH and Cl rate coefficients obtained by both techniques were indistinguishable, within experimental precision, and the average values were k1 = (7.82 +/- 0.55) * 10(-13) cm(3) molecule(-1) s(-1) and k2 = (3.45 +/- 0.24) * 10(-11) cm(3) molecule(-1) s(-1), respectively. The quoted uncertainties are at 95% level of confidence and include the estimated systematic uncertainties. An upper limit for the O3 rate coefficient was determined to be k3 < 9.0 * 10(-22) cm(3) molecule(-1) s(-1). In global warming potential (GWP) calculations, radiative efficiency (RE) was determined from the measured IR absorption cross-sections and treating HFIB both as long (LLC) and short (SLC) lived compounds, including estimated lifetime dependent factors in the SLC case. The HFIB lifetime was estimated from kinetic measurements considering merely the OH reaction, tauOH = 14.8 days and including both OH and Cl chemistry, taueff = 10.3 days. Therefore, GWP(HFIB,OH) and GWP(HFIB,eff) were estimated to be 4.1 (LLC) and 0.6 (SLC), as well as 2.8 (LLC) and 0.3 (SLC) for a hundred year time horizon. Moreover, the estimated photochemical ozone creation potential (epsilon(POCP)) of HFIB was calculated to be 4.60. Finally, HCHO and (CF3)2C(O) were identified as final oxidation products in both OH- and Cl-initiated oxidation, while HC(O)Cl was additionally observed in the Cl-initiated oxidation. PMID- 26372405 TI - Notice of Redundant Publication. PMID- 26372404 TI - Constructing an effective prevention mechanism for MSW lifecycle using failure mode and effects analysis. AB - Municipal solid waste in Taiwan is a valuable source of renewable energy. Phases of municipal solid waste lifecycle (classification, disposal, storage, collection and transportation) before incineration or landfilled face various potential failures. Applying a proper technique to eliminate or decrease potential failures is desirable and needed. Failure Modes and Effects Analysis to municipal solid waste lifecycle was found in literature. This study utilized the Failure Modes and Effects Analysis as a convenient technique for determining, classifying and analyzing common failures in the municipal solid waste lifecycle. As a result, an appropriate risk scoring of severity, occurrence, and detection of failure modes and computing the Risk Priority Number for identifying the high potential failure modes were made. Nineteen failure modes were identified, and nine of them were ranked as the priority items for improvement. Recommended actions for all failure modes were suggested. Occurrences of failures were remarkably reduced after implementing the procedure for six months. The results of this study have minimized potential failures and brought continuous improvement, thus achieving a better protection of the environment. PMID- 26372406 TI - The Acta Psychiatrica Scandinavica Trainee Advisory Board: education, mentoring, and experience with the editorial process. PMID- 26372407 TI - Effects of an Ai Chi fall prevention programme for patients with Parkinson's disease. AB - INTRODUCTION: One of the main symptoms of Parkinson's disease is the high incidence of falls occurring due to the decline of both static and dynamic balance. The aim of this study is to determine the effect of an Ai Chi programme designed to prevent falls in patients with Parkinson's disease by improving both functional independence and perception of physical pain. METHODS: Fifteen patients diagnosed with Parkinson's disease (Hoehn and Yahr stages 1-3) participated in a 10-week Ai Chi programme consisting of 30 to 45-minute aquatic exercise sessions twice a week. The assessment measures used in this study were the pain visual analogue scale (VAS), the Tinetti gait and balance assessment tool, and the Timed Get up and Go test. RESULTS: The results were calculated by applying the Friedman test to 3 related measurements: patients at baseline, at post-treatment (at the end of the 10 week programme) and after one month of follow-up. The data obtained showed a significant improvement (p <.001) in scores for pain perception, balance, and gait function after the treatment programme. Furthermore, patients continued to show significant improvements and the benefits remained at the one-month follow-up visit. CONCLUSION: Ai Chi is a promising and feasible aquatic treatment for improving pain perception, balance, and functional capacity in patients diagnosed with mild or moderate Parkinson's disease. PMID- 26372408 TI - Pitfalls of hypothesis tests and model selection on bootstrap samples: Causes and consequences in biometrical applications. AB - The bootstrap method has become a widely used tool applied in diverse areas where results based on asymptotic theory are scarce. It can be applied, for example, for assessing the variance of a statistic, a quantile of interest or for significance testing by resampling from the null hypothesis. Recently, some approaches have been proposed in the biometrical field where hypothesis testing or model selection is performed on a bootstrap sample as if it were the original sample. P-values computed from bootstrap samples have been used, for example, in the statistics and bioinformatics literature for ranking genes with respect to their differential expression, for estimating the variability of p-values and for model stability investigations. Procedures which make use of bootstrapped information criteria are often applied in model stability investigations and model averaging approaches as well as when estimating the error of model selection procedures which involve tuning parameters. From the literature, however, there is evidence that p-values and model selection criteria evaluated on bootstrap data sets do not represent what would be obtained on the original data or new data drawn from the overall population. We explain the reasons for this and, through the use of a real data set and simulations, we assess the practical impact on procedures relevant to biometrical applications in cases where it has not yet been studied. Moreover, we investigate the behavior of subsampling (i.e., drawing from a data set without replacement) as a potential alternative solution to the bootstrap for these procedures. PMID- 26372409 TI - Interobserver agreement of confocal laser endomicroscopy for detection of head and neck neoplasia. AB - OBJECTIVES/HYPOTHESIS: We have described the feasibility of using the probe-based confocal laser endomicroscopy (pCLE) in differentiating benign from malignant lesions of the head and neck. Therefore, we wanted to determine the interobserver agreement of pCLE offline images of noncancerous, precancerous, and cancerous lesions of the head and neck. STUDY DESIGN: Single tertiary referral center. METHODS: In the feasibility study, image criteria for nondysplasia, dysplasia, and cancer were defined. The pCLE was performed before lesions were biopsied. Fifty offline images and 10 videos of good quality were selected. Seven surgeons and one pathologist were asked to review and categorize the images into the three categories above. The overall accuracy of 29 offline pCLE images and six videos were compared with histopathology. Interobserver agreement and accuracy kappa (kappa) scores were measured with 95% confidence intervals (CI). RESULTS: There were six nondysplasia, seven dysplasia, and 11 squamous cell carcinoma (SCCA) cases, each with multiple images. There was substantial agreement between the eight reviewers on the pCLE images and videos (kappa = 0.66; 95% CI 0.51-0.82 and kappa = 0.71; 95% CI 0.42-0.97, respectively). The overall agreement with the final histopathology was also substantial for both the images and video sequences (kappa = 0.70; 95% CI 0.50-0.88 and kappa = 0.73; 95% CI 0.39-1.00, respectively). CONCLUSION: The ability to differentiate normal mucosa, dysplasia, and invasive SCCA using pCLE with high accuracy and reliability was demonstrated. This technology has the potential to decrease sampling error of lesions in the head and neck. This is the first study to test the reliability of this technology in mucosal lesions of the head and neck. LEVEL OF EVIDENCE: NA. Laryngoscope, 126:632-637, 2016. PMID- 26372410 TI - Case study of building of conservation coalitions to conserve ecological interactions. AB - We engaged experts in various fields of study (pollination ecology, chemical ecology, and ethnobotany), invited community participation, and provided environmental education in an effort to conserve an endangered birthwort (Aristolochia delavayi) and a vulnerable pipevine swallowtail (Byasa daemonius). Scientists studied the uptake and sequestration of the secondary metabolites aristolochic acids from A. delavayi leaves by different stages of pipevine swallowtail as a defense mechanism; low fruit set of the myophilous A. delavayi due to pollinator limitation; and the emission of chemical signals that attract parasitic wasps by the prepupae of B. daemonius. The results of these studies were part of an education program delivered by personnel of non-governmental organizations. The program was devised to deliver information to the public about the health risks of consuming A. delavayi individuals (aristolochic-acid associated cancers) and to establish a bridge between the public and scientific research. Following delivery of the program, the behavior of residents changed considerably. Community residents were involved in management activities, including participation in a program to promote understanding of ecological interactions between A. delavayi and B. daemonius; designing an in situ conservation site; monitoring A. delavayi and B. daemonius individuals; and promoting the natural fruit set of A. delavayi by scattering animal excrement to attract fly pollinators. The integration of scientific information and community participation appears to have resulted in an increase in abundance of threatened A. delavayi and B. daemonius populations. We believe the involvement of local people in conservation is necessary for successful species conservation. PMID- 26372412 TI - Stochastic Pharmacokinetic-Pharmacodynamic Analysis of the Effect of Transdermal Buprenorphine on Electroencephalogram and Analgesia. AB - BACKGROUND: The analgesic effect of opioids is often based on subjective one dimensional measurements. Electroencephalography (EEG) offers a possibility to objectively quantify the brain's activity before and after the administration of opioids. The aim of this study was to investigate the pharmacokinetic pharmacodynamic (PKPD) properties of the buprenorphine transdermal patch on resting EEG and pain tolerance. METHOD: Twenty-two healthy male subjects (mean age 23.1 +/- 3.8 years) were studied. They received a 144-hour buprenorphine (20 MUg/h) or placebo transdermal patch in this experimental, randomized, crossover, double-blind study. Skin heat pain tolerance was measured on the arm before the recordings of resting EEG. From the EEG, the ratio of slow and fast oscillations was calculated for further analysis. A population PKPD model with a stochastic differential equation for drug absorption from the patch was used to analyze the PK and PD data simultaneously by use of the statistical analysis package NONMEM. RESULTS: Buprenorphine increased EEG ratio (P = 0.0006) and skin pain tolerance (P = 0.0008) compared with placebo. The stochastic model adequately characterized the concentration-time and effect-time courses for both the skin heat stimulation and the resting EEG outcomes with variations in the drug's absorption rate during the 144-hour treatment period. As measured by the potency parameter, the EEG effect was 10 +/- 3 (median +/- SE) times more sensitive to buprenorphine than the skin pain test. CONCLUSIONS: Using a stochastic PKPD analysis, the effect of a 144-hour buprenorphine patch application on resting EEG and skin pain tolerance was quantified successfully. Both end points were affected by buprenorphine, although the resting EEG was more sensitive to buprenorphine. The stochastic PKPD analysis allowed the computation of a time-dependent variability in drug absorption from patch to blood. The data suggest that the resting EEG is an attractive and objective alternative for assessing opioid effect. PMID- 26372414 TI - Sexual behaviours and head and neck cancer: A systematic review and meta analysis. AB - Human papillomaviruses (HPV) are associated with head and neck cancers (H&NC). Transmission of HPV to the upper aerodigestive tract occurs plausibly through sexual contact, although epidemiologic evidence on the role of sexual behaviours in H&NC aetiology is inconsistent. We conducted a meta-analysis of studies examining the association between four indicators of sexual behaviours (number of sexual partners and oral sex partners, oral sex practice, and age at first intercourse) and H&NC. Summary odds ratios (OR) and 95% confidence intervals (CI) were estimated using fixed and random effects models for each indicator, contrasting 'highest' to 'lowest', 'ever' to 'never', or 'youngest' to 'oldest' categories. Twenty case-control studies were included out of 3838 identified publications. Using random effects models, summary ORs suggested an increased risk of H&NC for number of sexual partners [OR=1.29, 95% CI: 1.02-1.63] (19 studies) and number of oral sex partners [OR=1.69, 95% CI: 1.00-2.84] (5 studies), whereas no effect was observed with oral sex practice [OR=1.09, 95% CI: 0.88-1.35] (17 studies) and age at first intercourse [OR=1.40, 95% CI: 0.71-2.79] (6 studies). For number of sexual partners and oral sex practice, which were assessed in more studies, we further excluded studies contributing to heterogeneity and those not adjusted for age, sex, smoking, and alcohol consumption. The summary ORs were 0.95 (95% CI: 0.75-1.20) for number of sexual partners and 1.03 (95% CI: 0.84-1.26) for oral sex practice. Our findings highlight that observed associations might be partly attributed to confounding effects of sociodemographic and behavioural factors. PMID- 26372413 TI - Sonogenetics is a non-invasive approach to activating neurons in Caenorhabditis elegans. AB - A major challenge in neuroscience is to reliably activate individual neurons, particularly those in deeper brain regions. Current optogenetic approaches require invasive surgical procedures to deliver light of specific wavelengths to target cells to activate or silence them. Here, we demonstrate the use of low pressure ultrasound as a non-invasive trigger to activate specific ultrasonically sensitized neurons in the nematode, Caenorhabditis elegans. We first show that wild-type animals are insensitive to low-pressure ultrasound and require gas filled microbubbles to transduce the ultrasound wave. We find that neuron specific misexpression of TRP-4, the pore-forming subunit of a mechanotransduction channel, sensitizes neurons to ultrasound stimulus, resulting in behavioural outputs. Furthermore, we use this approach to manipulate the function of sensory neurons and interneurons and identify a role for PVD sensory neurons in modifying locomotory behaviours. We suggest that this method can be broadly applied to manipulate cellular functions in vivo. PMID- 26372415 TI - Risk of lymphoma subtypes and dietary habits in a Mediterranean area. AB - BACKGROUND: Previous studies have suggested that diet might affect risk of lymphoma subtypes. We investigated risk of lymphoma and its major subtypes associated with diet in the Mediterranean island of Sardinia, Italy. METHODS: In 1998-2004, 322 incident lymphoma cases and 446 randomly selected population controls participated in a case-control study on lymphoma etiology in central southern Sardinia. Questionnaire interviews included frequency of intake of 112 food items. Risk associated with individual dietary items and groups thereof was explored by unconditional and polytomous logistic regression analysis, adjusting by age, gender and education. RESULTS: We observed an upward trend in risk of lymphoma (all subtypes combined) and B-cell lymphoma with frequency of intake of well done grilled/roasted chicken (p for trend=0.01), and pizza (p for trend=0.047), Neither adherence to Mediterranean diet nor a frequent intake of its individual components conveyed protection. We detected heterogeneity in risk associated with several food items and groups thereof by lymphoma subtypes although we could not rule out chance as responsible for the observed direct or inverse associations. CONCLUSIONS: Adherence to a Mediterranean diet does not seem to convey protection against the development of lymphoma. The association with specific food items might vary by lymphoma subtype. PMID- 26372416 TI - Improved outcomes after low-concentration hypochlorous acid nasal irrigation in pediatric chronic sinusitis. AB - OBJECTIVES/HYPOTHESIS: We aimed to evaluate the effectiveness of low concentration hypochlorous acid (HOCl) nasal irrigation compared to isotonic normal saline for pediatric chronic rhinosinusitis. STUDY DESIGN: This was a randomized, prospective, active-controlled study. METHODS: This study investigated the effectiveness of 4 weeks of low-concentration hypochlorous irrigation by analyzing five categorized subjective symptoms and x-ray findings in pediatric patients with rhinosinusitis. Thirty-seven patients were enrolled, and 26 patients successfully completed the study. RESULTS: Total symptom scores significantly improved with both HOCl and normal saline nasal irrigation, but there was no difference between the two groups. X-ray scores also improved in both groups; improvement was much greater in the HOCl group than the placebo group. CONCLUSIONS: Nasal irrigation with HOCl is an effective adjuvant treatment compared to isotonic normal saline for pediatric sinusitis. LEVEL OF EVIDENCE: 1b. PMID- 26372417 TI - Trends in Pap Testing Over Time for Women With and Without Chronic Disability. AB - INTRODUCTION: Data from 20 years ago--shortly after passage of the Americans with Disabilities Act--showed that women with significant mobility disability had 40% lower Pap test rates than other women. METHODS: To examine whether disability disparities in Pap test rates have diminished over time, this study analyzed National Health Interview Survey responses from selected years between 1998 and 2010 from women aged 21-65 years without histories of cervical cancer or hysterectomy. Seven chronic disability types were identified using self-reported functional impairments or participation limitations. Self-reported Pap testing within the previous 3 years was studied. Bivariable analyses and multivariable logistic regression analyses controlling for sociodemographic variables were conducted in 2014. RESULTS: Rates of all chronic disability types increased over time. Pap test rates remained relatively constant over time for all women, holding around 84%-87%. Bivariable analyses found statistically significantly lower rates of Pap testing for women with disability compared with nondisabled women. Multivariable analyses failed to find consistent evidence of lower Pap test rates among women across disability types compared with nondisabled women. In 2010, the AOR for reporting Pap testing for women noting the most severe movement difficulty compared with nondisabled women was 0.35 (95% CI=0.15, 0.79). However, the AOR for this disability type varied over time. CONCLUSIONS: Little has changed over time in Pap test rates for all women. Women with certain disabilities continue to experience disparities compared with nondisabled women in receipt of this important screening test. PMID- 26372418 TI - Morphine Preconditioning Downregulates MicroRNA-134 Expression Against Oxygen Glucose Deprivation Injuries in Cultured Neurons of Mice. AB - BACKGROUND: Brain protection by narcotics such as morphine is clinically relevant due to the extensive use of narcotics in the perioperative period. Morphine preconditioning induces neuroprotection in neurons, but it remains uncertain whether microRNA-134 (miR-134) is involved in morphine preconditioning against oxygen-glucose deprivation-induced injuries in primary cortical neurons of mice. The present study examined this issue. MATERIALS AND METHODS: After cortical neurons of mice were cultured in vitro for 6 days, the neurons were transfected by respective virus vector, such as lentiviral vector (LV)-miR-control-GFP, LV pre-miR-134-GFP, LV-pre-miR-134-inhibitor-GFP for 24 hours; after being normally cultured for 3 days again, morphine preconditioning was performed by incubating the transfected primary neurons with morphine (3 MUM) for 1 hour, and then neuronal cells were exposed to oxygen-glucose deprivation (OGD) for 1 hour and oxygen-glucose recovery for 12 hours. The neuronal cells survival rate and the amount of apoptotic neurons were determined by MTT assay or TUNEL staining at designated time; and the expression levels of miR-134 were detected using real time reverse transcription polymerase chain reaction at the same time. RESULTS: The neuronal cell survival rate was significantly higher, and the amount of apoptotic neurons was significantly decreased in neurons preconditioned with morphine before OGD than that of OGD alone. The neuroprotection induced by morphine preconditioning was partially blocked by upregulating miR-134 expression, and was enhanced by downregulating miR-134 expression. The expression of miR-134 was significantly decreased in morphine-preconditioned neurons alone without transfection. CONCLUSIONS: By downregulating miR-134 expression, morphine preconditioning protects primary cortical neurons of mice against injuries induced by OGD. PMID- 26372419 TI - Soil as an inexhaustible and high-performance anode material for Li-ion batteries. AB - Herein, we demonstrate that by a simple treatment of heating and ball-milling, soil is endowed with a 77.2% degree of defects and acts as a high-performance anode material for soil/Li half cells and 18650-type LiNi0.915Co0.075Al0.1O2 (NCA)/soil full batteries that displayed a high and stable capacity of 3200 mA h (corresponding to 176 W h kg(-1) and 522 W h L(-1)) in the 200th cycle at a high current of 4 A. PMID- 26372421 TI - A mild and fast continuous-flow trifluoromethylation of coumarins with the CF3 radical derived from CF3SO2Na and TBHP. AB - A mild and fast Cu(I)-catalyzed trifluoromethylation of coumarins with CF3SO2Na and TBHP in a continuous-flow reactor has been developed. This method is experimentally simple and carried out under mild conditions, affording the corresponding products in moderate to good yields, and showing wide substrate tolerance. The scale-up flow process results in an isolated yield of 68% and a productivity of 305 mg h(-1) of 3-trifluoromethyl-7-diethylamino-4-methyl coumarin when the concentration was increased five-fold. Given these features and the widespread applications of coumarins, this method may find use from laboratory to manufacturing. PMID- 26372420 TI - Reprint of 'Model of unidirectional block formation leading to reentrant ventricular tachycardia in the infarct border zone of postinfarction canine hearts'. AB - BACKGROUND: When the infarct border zone is stimulated prematurely, a unidirectional block line (UBL) can form and lead to double-loop (figure-of eight) reentrant ventricular tachycardia (VT) with a central isthmus. The isthmus is composed of an entrance, center, and exit. It was hypothesized that for certain stimulus site locations and coupling intervals, the UBL would coincide with the isthmus entrance boundary, where infarct border zone thickness changes from thin-to-thick in the travel direction of the premature stimulus wavefront. METHOD: A quantitative model was developed to describe how thin-to-thick changes in the border zone result in critically convex wavefront curvature leading to conduction block, which is dependent upon coupling interval. The model was tested in 12 retrospectively analyzed postinfarction canine experiments. Electrical activation was mapped for premature stimulation and for the first reentrant VT cycle. The relationship of functional conduction block forming during premature stimulation to functional block during reentrant VT was quantified. RESULTS: For an appropriately placed stimulus, in accord with model predictions: 1. The UBL and reentrant VT isthmus lateral boundaries overlapped (error: 4.8+/-5.7mm). 2. The UBL leading edge coincided with the distal isthmus where the center-entrance boundary would be expected to occur. 3. The mean coupling interval was 164.6+/ 11.0ms during premature stimulation and 190.7+/-20.4ms during the first reentrant VT cycle, in accord with model calculations, which resulted in critically convex wavefront curvature and functional conduction block, respectively, at the location of the isthmus entrance boundary and at the lateral isthmus edges. DISCUSSION: Reentrant VT onset following premature stimulation can be explained by the presence of critically convex wavefront curvature and unidirectional block at the isthmus entrance boundary when the premature stimulation interval is sufficiently short. The double-loop reentrant circuit pattern is a consequence of wavefront bifurcation around this UBL followed by coalescence, and then impulse propagation through the isthmus. The wavefront is blocked from propagating laterally away from the isthmus by sharp increases in border zone thickness, which results in critically convex wavefront curvature at VT cycle lengths. PMID- 26372422 TI - Particle-image velocimetry investigation of the fluid-structure interaction mechanisms of a natural owl wing. AB - The increasing interest in the development of small flying air vehicles has given rise to a strong need to thoroughly understand low-speed aerodynamics. The barn owl is a well-known example of a biological system that possesses a high level of adaptation to its habitat and as such can inspire future small-scale air vehicle design. The combination of the owl-specific wing geometry and plumage adaptations with the flexibility of the wing structure yields a highly complex flow field, still enabling the owl to perform stable and at the same time silent low-speed gliding flight. To investigate the effects leading to such a characteristic flight, time-resolved stereoscopic particle-image velocimetry (TR-SPIV) measurements are performed on a prepared natural owl wing in a range of angles of attack 0 degrees <= alpha <= 6 degrees and Reynolds numbers 40,000 <= Re(c) <= 120,000 based on the chord length at a position located at 30% of the halfspan from the owl's body. The flow field does not show any flow separation on the suction side, whereas flow separation is found on the pressure side for all investigated cases. The flow field on the pressure side is characterized by large scale vortices which interact with the flexible wing structure. The good agreement of the shedding frequency of the pressure side vortices with the frequency of the trailing-edge deflection indicates that the structural deformation is induced by the flow field on the pressure side. Additionally, the reduction of the time-averaged mean wing curvature at high Reynolds numbers indicates a passive lift-control mechanism that provides constant lift in the entire flight envelope of the owl. PMID- 26372423 TI - Two-Photon Photochemistry of CdSe Quantum Dots. AB - The two-photon photochemistry of CdSe quantum dots (QDs) has been systematically studied. We find that upon intense irradiation CdSe quantum dots that absorb two or more visible photons undergo photodarkening. The quantum yield for this process is on the order of 6% in chloroform and much smaller in nonpolar solvents, such as octane. An analysis of the energetics indicates that, following two-photon excitation, the biexciton undergoes an Auger process producing a hot hole. This hot hole is ejected to a surface-bound TOP ligand, forming a QD( )/TOP(+) contact ion pair that separates in chloroform, but not in octane. The charged and deligated QD is dark, resulting in the overall photodarkening. This photodarkening reaction may or may not be reversible, depending on what other chemical components are in the irradiated solution. The quantum dot concentration dependence and PL decay kinetics indicate that charge recombination occurs rapidly, followed by ligand reattachment and reorganization on a longer (tens of minutes) time scale. The relation of this mechanism to one-photon photochemistry is also discussed. PMID- 26372424 TI - Negative regulation of natural killer cell in tumor tissue and peripheral blood of oral squamous cell carcinoma. AB - Natural killer (NK) cells are the key lymphocytes in solid tumors. Its activity is regulated by both germline encoded receptors and cytokine microenvironment. We conducted a case-control study to investigate the activation status of NK cell in oral squamous cell carcinoma (OSCC). NK cell activation was assessed in context of NK cell cytotoxicity and transcript expression of NK cell receptors (NKp46 and KIRs) and NK cell associated cytokines (IL-1beta, IL-2, IL-10, IL-12beta, IL-15, IL-18, IL-21, IFN-gamma, TNF-alpha and TGF-beta). The results revealed possible mechanisms involved in reduced NK cell activation in peripheral circulation: quantitative deficiency of NK cell number and lowered cytotoxicity together with qualitative NK impairments caused by--(1) decreased expression of NK activating receptor NKp46, (2) increased expression of NK suppressive cytokines--IL-10 and TGF-beta and (3) induction of FOXP3(+)CTLA4(+) suppressor cells. On the other hand, in the tumor tissue, escape of NK immune surveillance appeared to be modulated by upregulation of TGF-beta and IL-10 together with downregulation of NK cell activating cytokines (IL-2, IL-12beta, IL-15, IL-18, IL-21 and IFN-gamma) and NK receptors (NKp46 and KIRs). In addition, our study supported the earlier contention that TNF-alpha and IL-1beta expression levels may be used as markers of malignant transformation in oral leukoplakia. In conclusion, the study provided an insight into the negative regulation of NK cell in tumor tissue and peripheral blood of OSCC patients, which can be exploited to boost the current NK cell and cytokine based immunotherapy for the treatment of oral cancer. PMID- 26372425 TI - Plasmon-Enhanced Second-Harmonic Generation Nanorulers with Ultrahigh Sensitivities. AB - Attainment of spatial resolutions far below diffraction limits by means of optical methods constitutes a challenging task. Here, we design nonlinear nanorulers that are capable of accomplishing approximately 1 nm resolutions by utilizing the mechanism of plasmon-enhanced second-harmonic generation (PESHG). Through introducing Au@SiO2 (core@shell) shell-isolated nanoparticles, we strive to maneuver electric-field-related gap modes such that a reliable relationship between PESHG responses and gap sizes, represented by "PESHG nanoruler equation", can be obtained. Additionally validated by both experiments and simulations, we have transferred "hot spots" to the film-nanoparticle-gap region, ensuring that retrieved PESHG emissions nearly exclusively originate from this region and are significantly amplified. The PESHG nanoruler can be potentially developed as an ultrasensitive optical method for measuring nanoscale distances with higher spectral accuracies and signal-to-noise ratios. PMID- 26372426 TI - Parameters Selection for Bivariate Multiscale Entropy Analysis of Postural Fluctuations in Fallers and Non-Fallers Older Adults. AB - Entropy measures are often used to quantify the regularity of postural sway time series. Recent methodological developments provided both multivariate and multiscale approaches allowing the extraction of complexity features from physiological signals; see "Dynamical complexity of human responses: A multivariate data-adaptive framework," in Bulletin of Polish Academy of Science and Technology, vol. 60, p. 433, 2012. The resulting entropy measures are good candidates for the analysis of bivariate postural sway signals exhibiting nonstationarity and multiscale properties. These methods are dependant on several input parameters such as embedding parameters. Using two data sets collected from institutionalized frail older adults, we numerically investigate the behavior of a recent multivariate and multiscale entropy estimator; see "Multivariate multiscale entropy: A tool for complexity analysis of multichannel data," Physics Review E, vol. 84, p. 061918, 2011. We propose criteria for the selection of the input parameters. Using these optimal parameters, we statistically compare the multivariate and multiscale entropy values of postural sway data of non-faller subjects to those of fallers. These two groups are discriminated by the resulting measures over multiple time scales. We also demonstrate that the typical parameter settings proposed in the literature lead to entropy measures that do not distinguish the two groups. This last result confirms the importance of the selection of appropriate input parameters. PMID- 26372427 TI - Locomotor Adaptation to an Asymmetric Force on the Human Pelvis Directed Along the Right Leg. AB - In this work, we study locomotor adaptation in healthy adults when an asymmetric force vector is applied to the pelvis directed along the right leg. A cable driven Active Tethered Pelvic Assist Device (A-TPAD) is used to apply an external force on the pelvis, specific to a subject's gait pattern. The force vector is intended to provide external weight bearing during walking and modify the durations of limb supports. The motivation is to use this paradigm to improve weight bearing and stance phase symmetry in individuals with hemiparesis. An experiment with nine healthy subjects was conducted. The results show significant changes in the gait kinematics and kinetics while the healthy subjects developed temporal and spatial asymmetry in gait pattern in response to the applied force vector. This was followed by aftereffects once the applied force vector was removed. The adaptation to the applied force resulted in asymmetry in stance phase timing and lower limb muscle activity. We believe this paradigm, when extended to individuals with hemiparesis, can show improvements in weight bearing capability with positive effects on gait symmetry and walking speed. PMID- 26372428 TI - Classifying Regularized Sensor Covariance Matrices: An Alternative to CSP. AB - Common spatial patterns (CSP) is a commonly used technique for classifying imagined movement type brain-computer interface (BCI) datasets. It has been very successful with many extensions and improvements on the basic technique. However, a drawback of CSP is that the signal processing pipeline contains two supervised learning stages: the first in which class- relevant spatial filters are learned and a second in which a classifier is used to classify the filtered variances. This may lead to potential overfitting issues, which are generally avoided by limiting CSP to only a few filters. PMID- 26372429 TI - Ambulatory Gait Behavior in Patients With Dementia: A Comparison With Parkinson's Disease. AB - Accelerometry-based gait analysis is a promising approach in obtaining insightful information on the gait characteristics of patients with neurological disorders such as dementia and Parkinson's disease (PD). In order to improve its practical use outside the laboratory or hospital, it is required to design new metrics capable of quantifying ambulatory gait and their extraction procedures from long term acceleration data. This paper presents a gait analysis method developed for such a purpose. Our system is based on a single trunk-mounted accelerometer and analytical algorithm for the assessment of gait behavior that may be context dependent. The algorithm consists of the detection of gait peaks from acceleration data and the analysis of multimodal patterns in the relationship between gait cycle and vertical gait acceleration. A set of six new measures can be obtained by applying the algorithm to a 24-h motion signal. To examine the performance and utility of our method, we recorded acceleration data from 13 healthy, 26 PD, and 26 mild cognitive impairment or dementia subjects. Each patient group was further classified into two, comprising 13 members each, according to the severity of the disease, and the gait behavior of the five groups was compared. We found that the normal, PD, and MCI/dementia groups show characteristic walking patterns which can be distinguished from one another by the developed gait measure set. We also examined conventional parameters such as gait acceleration, gait cycle, and gait variability, but failed to reproduce the distinct differences among the five groups. These findings suggest that the proposed gait analysis may be useful in capturing disease-specific gait features in a community setting. PMID- 26372430 TI - Effects of Different Tactile Feedback on Myoelectric Closed-Loop Control for Grasping Based on Electrotactile Stimulation. AB - Closed-loop control is important for amputees to manipulate myoelectric prostheses intuitively and dexterously. Tactile feedback can help amputees improve myoelectric control performance for grasping objects. To investigate the effects of different tactile feedback, we performed experiments on six amputees and six able-bodied subjects via electrotactile stimulation. Using a virtual environment, six kinds of objects with different weights and stiffnesses were used for grasping tasks. Five feedback conditions (no feedback, pressure feedback, slip feedback, pressure + slip feedback, and vision feedback) were considered. Nine evaluation indexes and three control objectives (rapidity, economy, and stability) were proposed. Under the five feedback conditions, our study investigated four issues: 1) three types of grasping-related failures; 2) four types of grasping-related time measures; 3) average grasping force; 4) standard deviation of the grasping force. Results indicate that: 1) slip feedback is better than pressure feedback; 2) pressure + slip feedback can improve grasping rapidity; 3) slip feedback significantly contributes to grasping economy and stability; and 4) pressure + slip feedback can perform as well as vision feedback. PMID- 26372431 TI - Charting the Course of Improved Health for Children in Foster Care. PMID- 26372432 TI - Flexible Infrared Responsive Multi-Walled Carbon Nanotube/Form-Stable Phase Change Material Nanocomposites. AB - Flexible infrared (IR)-responsive materials, such as polymer nanocomposites, that exhibit high levels of IR responses and short response times are highly desirable for various IR sensing applications. However, the IR-induced photoresponses of carbon nanotube (CNT)/polymer nanocomposites are typically limited to 25%. Herein, we report on a family of unique nanocomposite films consisting of multi walled carbon nanotubes (MWCNTs) uniformly distributed in a form-stable phase change material (PCM) that exhibited rapid, dramatic, reversible, and cyclic IR regulated responses in air. The 3 wt % MWCNT/PCM nanocomposite films demonstrated cyclic, IR-regulated on/off electrical conductivity ratios of 11.6 +/- 0.6 and 570.0 +/- 70.5 times at IR powers of 7.3 and 23.6 mW/mm(2), respectively. The excellent performances exhibited by the MWCNT/PCM nanocomposite films were largely attributed to the IR-regulated cyclic and reversible form-stable phase transitions occurring in the PCM matrix due to MWCNT's excellent photoabsorption and thermal conversion capabilities, which subsequently affected the thickness of the interfacial PCM between adjacent conductive MWCNTs and thus the electron tunneling efficiency between the MWCNTs. Our findings suggest that these unique MWCNT/PCM nanocomposites offer promising new options for high-performance and flexible optoelectronic devices, including thermal imaging, IR sensing, and optical communication. PMID- 26372433 TI - The Role of the Hand During Freestyle Swimming. AB - The connections between swimming technique and the fluid dynamical interactions they generate are important for assisting performance improvement. Computational fluid dynamics (CFD) modeling provides a controlled and unobtrusive way for understanding the fundamentals of swimming. A coupled biomechanical-smoothed particle hydrodynamics (SPH) fluid model is used to analyze the thrust and drag generation of a freestyle swimmer. The swimmer model was generated using a three dimensional laser body scan of the athlete and digitization of multi-angle video footage. Two large distinct peaks in net streamwise thrust are found during the stroke, which coincide with the underwater arm strokes. The hand motions generate vortical structures that travel along the body toward the kicking legs and the hands are shown to produce thrust using both lift and drag. These findings advance understanding of the freestyle stroke and may be used to improve athlete technique. PMID- 26372434 TI - Genetic analysis of the bicarbonate secreting anion exchanger SLC26A6 in chronic pancreatitis. AB - BACKGROUND: Pancreatic ductal HCO3(-) secretion is critically dependent on the cystic fibrosis transmembrane conductance regulator chloride channel (CFTR) and the solute-linked carrier 26 member 6 anion transporter (SLC26A6). Deterioration of HCO3(-) secretion is observed in chronic pancreatitis (CP), and CFTR mutations increase CP risk. Therefore, SLC26A6 is a reasonable candidate for a CP susceptibility gene, which has not been investigated in CP patients so far. METHODS: As a first screening cohort, 106 subjects with CP and 99 control subjects with no pancreatic disease were recruited from the Hungarian National Pancreas Registry. In 60 non-alcoholic CP cases the entire SLC26A6 coding region was sequenced. In the Hungarian cohort variants c.616G > A (p.V206M) and c.1191C > A (p.P397=) were further genotyped by restriction fragment length polymorphism analysis. In a German replication cohort all exons were sequenced in 40 non alcoholic CP cases and variant c.616G > A (p.V206M) was further analyzed by sequencing in 321 CP cases and 171 controls. RESULTS: Sequencing of the entire coding region revealed four common variants: intronic variants c.23 + 78_110del, c.183-4C > A, c.1134 + 32C > A, and missense variant c.616G > A (p.V206M) which were found in linkage disequilibrium indicating a conserved haplotype. The distribution of the haplotype did not show a significant difference between patients and controls in the two cohorts. A synonymous variant c.1191C > A (p.P397=) and two intronic variants c.1248 + 9_20del and c.-10C > T were detected in single cases. CONCLUSION: Our data show that SLC26A6 variants do not alter the risk for the development of CP. PMID- 26372435 TI - Initial Report of Pencil Beam Scanning Proton Therapy for Posthysterectomy Patients With Gynecologic Cancer. AB - PURPOSE: To report the acute toxicities associated with pencil beam scanning proton beam radiation therapy (PBS) for whole pelvis radiation therapy in women with gynecologic cancers and the results of a dosimetric comparison of PBS versus intensity modulated radiation therapy (IMRT) plans. METHODS AND MATERIALS: Eleven patients with posthysterectomy gynecologic cancer received PBS to the whole pelvis. The patients received a dose of 45 to 50.4 Gy relative biological effectiveness (RBE) in 1.8 Gy (RBE) daily fractions. Acute toxicity was scored according to the Common Terminology Criteria for Adverse Events, version 4. A dosimetric comparison between a 2-field posterior oblique beam PBS and an IMRT plan was conducted. The Wilcoxon signed rank test was used to assess the potential dosimetric differences between the 2 plans and PBS target coverage robustness relative to setup uncertainties. RESULTS: The median patient age was 55 years (range 23-76). The primary site was cervical in 7, vaginal in 1, and endometrial in 3. Of the 11 patients, 7 received concurrent cisplatin, 1 each received sandwich carboplatin and paclitaxel chemotherapy, both sandwich and concurrent chemotherapy, and concurrent and adjuvant chemotherapy, and 1 received no chemotherapy. All patients completed treatment. Of the 9 patients who received concurrent chemotherapy, the rate of grade 2 and 3 hematologic toxicities was 33% and 11%, respectively. One patient (9%) developed grade 3 acute gastrointestinal toxicity; no patient developed grade >=3 genitourinary toxicity. The volume of pelvic bone marrow, bladder, and small bowel receiving 10 to 30 Gy was significantly lower with PBS than with intensity modulated radiation therapy (P<.001). The target coverage for all PBS plans was robust relative to the setup uncertainties (P>.05) with the clinical target volume mean dose percentage received by 95% and 98% of the target volume coverage changes within 2% for the individual plans. CONCLUSIONS: Our results have demonstrated the clinical feasibility of PBS and the dosimetric advantages, especially for the low-dose sparing of normal tissues in the pelvis with the target robustness maintained relative to the setup uncertainties. Future studies with larger patient numbers are planned to further validate our preliminary findings. PMID- 26372436 TI - Biological therapy and dentistry: a review paper. AB - In recent years, a new class of drugs has revolutionized the treatment of autoimmune, allergic, infectious, and many more diseases. This new class of drugs is made of 3 groups-cytokines, monoclonal antibodies, and fusion proteins-that may target special damaged cells but not all the cells. These drugs may have side effects such as infection, hypersensitivity, hematologic disorders, cancer, hepatotoxicity, and neurologic disorders. However, there is not enough evidence or long-term studies of the mechanism of action and side effects of these drugs. Patients receiving biological therapies may need special consideration in dentistry. This paper is a review of the classification, mechanism of action, and side effects of these drugs and dental consideration for patients receiving biological therapies. PMID- 26372437 TI - Epidemiology, prognostic factors, and management of malignant odontogenic tumors: an analysis of 295 cases. AB - OBJECTIVE: To determine the demographic characteristics, prognostic factors, and management for patients diagnosed with a malignant odontogenic tumor (MOT). STUDY DESIGN: The Surveillance, Epidemiology, and End Results (SEER) registry was reviewed for patients diagnosed with MOT from 1973 to 2011. Kaplan-Meier and multivariate Cox regression analyses were performed on patient demographic characteristics and pathologic variables. RESULTS: The SEER database identified 295 MOT patients. The mean age at diagnosis was 50.5 years (range 5-89 years). Of these patients, 61.7% were male and 38.3% were female. The racial composition was 66.4% White, 22% Black, 6.1% Asian, 3.1% Pacific Islander, 0.3% Native American, and 2.1% Other/Unknown. Kaplan-Meier analysis found an overall survival (OS) and disease-specific survival (DSS) at 5 years of 54% and 67%, respectively. Multivariate analysis of the entire cohort found that age and stage were predictors of OS and that age was a predictor for DSS. For stage I/II MOTs, age and surgical therapy were predictors of OS and DSS, respectively. CONCLUSIONS: Here we report the largest study to date investigating demographic characteristics, prognostic factors, and management of MOT patients. Determinants of survival for OS and DSS include age, stage, and surgical therapy. PMID- 26372438 TI - Emergency Department Management Of Acute Infective Endocarditis. AB - Infective endocarditis has a high rate of mortality, and most patients suspected of having the disease will require hospital admission. This review examines the literature as it pertains specifically to emergency clinicians who must maintain vigilance for risk factors and obtain a thorough history, including use of intravenous drugs, in order to guide the workup and treatment. Properly obtained cultures are critical during the evaluation, as they direct the course of antibiotic therapy. Although transthoracic echocardiography is widely available in United States emergency departments, it is not sensitive or specific enough to rule out a diagnosis of infective endocarditis. In high-risk patients, transesophageal echocardiography should be considered. PMID- 26372439 TI - [An uncommon presentation of a syndrome very rare]. PMID- 26372440 TI - [Promoting healthy eating habits for adolescents in primary care]. PMID- 26372441 TI - Service provider perspectives on post-abortion contraception in Nepal. AB - The government of Nepal has articulated a commitment to the provision of post abortion contraception since the implementation of a legal safe abortion policy in 2004. Despite this, gaps in services remain. This study examined the perspectives of abortion service providers and administrators regarding strengths and shortcomings of post-abortion contraceptive service provision. In-depth interviews were conducted with 24 abortion providers and administrators at four major health facilities that provide legal abortion in Nepal. Facility factors perceived to impact post-abortion contraceptive services included on-site availability of contraceptive supplies, dedicated and well-trained staff and adequate infrastructure. Cultural norms emerged as influencing contraceptive demand by patients, including method use being unacceptable for women whose husbands migrate and limited decision-making power among women. Service providers described their personal views on appropriate childbearing and the use of specific contraceptive methods that influenced counselling. Findings suggest that improvements to a facility's infrastructure and training to address provider biases and misinformation may improve post-abortion family planning uptake. Adapting services to be sensitive to cultural expectations and norms may help address some barriers to contraceptive use. More research is needed to determine how to best meet the contraceptive needs of women who have infrequent sexual activity or who may face stigma for using family planning, including adolescents, unmarried women and women whose husbands migrate. PMID- 26372442 TI - Recent developments in the analysis of musty odour compounds in water and wine: A review. AB - One of the most common taints in foods is a musty or earthy odour, which is commonly associated with the activity of microorganisms. Liquid foods, particularly wine and water, can be affected by this defect due to the presence of certain aromatic organic compounds at very low concentrations (ng/L) consistent with human threshold perception levels. The volatile compounds responsible for a mouldy off-aroma include approximately 20 compounds, namely, haloanisoles, geosmin, 2-methylisoborneol, several alkyl-methoxypyrazines, 1 octen-3-ol, 1-octen-3-one, trans-octenol, 3-octanone, fenchol and fenchone. Methods for determining these very low concentrations of odour compounds must be extremely sensitive and selective with efficient preconcentration treatments. A number of extraction techniques based on LLME (liquid-liquid microextraction), SPME (solid-phase microextraction) or SBSE (stir-bar sorptive extraction) can be applied and should be selected on a case-by-case basis. Moreover, recent developments in GC instrumentation coupled to different detection systems can effectively increase the selectivity and sensitivity of the analysis of target compounds. PMID- 26372443 TI - Enantioseparation of basic chiral drugs on a carbamoylated erythromycin-zirconia hybrid monolith using capillary electrochromatography. AB - An organic-inorganic hybrid monolithic column was prepared within the confines of a capillary via a single-step in situ sol-gel approach using zirconium tetrabutoxide as a precursor to compose the inorganic backbone and 3 triethoxysilylpropyl carbamoylated derivative of erythromycin (TEOSPC-ERY) as a co-precursor to introduce the organic chiral selector moiety in the zirconia backbone. The resulting carbamoylated ERY-zirconia hybrid monolith (ERY-ZHM) showed homogeneous morphology with well-defined through pores and was tightly connected with the inner wall of the capillary. The column was employed for capillary electrochromatographic enantioseparation of six basic chiral drugs in mobile phases (MPs) consisting of acetonitrile (ACN) and triethylammonium acetate (TEAA) buffer. The effects of composition of MP and applied voltage on chiral separation were investigated by using propranolol as a representative analyte. The highest resolution (Rs=3.33) was obtained with a MP consisting of 10/90 (v/v) ACN/TEAA buffer (10mM, pH 7), 10 kV applied voltage and 25 degrees C capillary temperature. The relative standard deviations for resolution values regarding run to run, day to day, column to column and batch to batch repeatability were 0.41%, 0.89%, 1.80% and 2.26% (for n=3), respectively, indicating satisfactory stability of columns and reproducibility of column preparation process. PMID- 26372444 TI - Non-targeted screening approaches for contaminants and adulterants in food using liquid chromatography hyphenated to high resolution mass spectrometry. AB - The majority of analytical methods for food safety monitor the presence of a specific compound or defined set of compounds. Non-targeted screening methods are complementary to these approaches by detecting and identifying unexpected compounds present in food matrices that may be harmful to public health. However, the development and implementation of generalized non-targeted screening workflows are particularly challenging, especially for food matrices due to inherent sample complexity and diversity and a large analyte concentration range. One approach that can be implemented is liquid chromatography coupled to high resolution mass spectrometry, which serves to reduce this complexity and is capable of generating molecular formulae for compounds of interest. Current capabilities, strategies, and challenges will be reviewed for sample preparation, mass spectrometry, chromatography, and data processing workflows. Considerations to increase the accuracy and speed of identifying unknown molecular species will also be addressed, including suggestions for achieving sufficient data quality for non-targeted screening applications. PMID- 26372445 TI - Integrative analysis of proteomics and metabolomics of anaphylactoid reaction induced by Xuesaitong injection. AB - Injection with natural compounds is an important method in the application of natural medicine, but its adverse drug reactions (ADRs) occur frequently, particularly the anaphylactoid reaction, which accounts for more than 77% of all reactions and has become a serious threat to public health. Here, the Xuesaitong injection (XSTI) was employed as an example to elucidate its anaphylactoid mechanism and look for potential biomarkers to assay the anaphylactoid reaction of herbal medicine injection by proteomics and metabolomics. These results disclosed that 13 differential proteins and 28 metabolites, which were further approved using the ELISA method and reference standards, respectively, were suggested as potential biomarkers to examine the anaphylactoid mechanism. The up regulated expression of Gpx1, Sc5b9, C4d and down-regulated expression of F12, Kng1, C2 and C6 revealed that the XSTI-induced anaphylactoid reaction occurs via direct stimulation, complement and the kallikrein-kinin pathway. In addition, substances that induce an anaphylactoid effect include histamine, LTB4, uric acid and other drugs, which have been confirmed to be involved in arginine and proline metabolism, histidine metabolism, arachidonic acid metabolism purine metabolism and the TCA cycle. Furthermore, separation experiments have indicated that 10-kDa molecules of XSTI are the main allergenic factor inducing an anaphylactoid reaction. PMID- 26372447 TI - Estimation of alkane-water logP for neutral, acidic, and basic compounds using an alkylated polystyrene-divinylbenzene high-performance liquid chromatography column. AB - Reliable HPLC methods are available to estimate octanol-water partition coefficients, but there is no comparable method for alkane-water partition coefficients that is accurate and applicable across a broad span of logP(alk). This study describes a high-throughput method for determining HPLC-logP(alk), a chromatographic parameter closely related to logP(alk), using an alkylated polystyrene-divinylbenzene column and fast acetonitrile gradient. A structurally diverse set of neutral, acidic, and basic compounds was analyzed under ionization suppressing pH conditions. In this chromatographic system, the relationship between gradient retention time and isocratic logk was essentially linear. Thus, gradient retention time could be used as the sole input needed to determine an apparent logP(alk)by HPLC. HPLC-logP(alk) showed linear correlation (R(2)>0.96, n=59) with reference logP(alk) values from shake-flask measurements over 8 orders of magnitude, ranging from -2.3 to +5.7. Linear solvation energy relationship (LSER) analysis revealed that the relative contributions of intermolecular forces effecting retention in the fast gradient system or its corresponding isocratic variant were highly similar to those governing partition in bulk alkane-water. PMID- 26372446 TI - Theoretical evaluation of peak capacity improvements by use of liquid chromatography combined with drift tube ion mobility-mass spectrometry. AB - In the domain of liquid phase separations, the quality of separation obtainable is most readily gauged by consideration of classical chromatographic peak capacity theory. Column-based multidimensional strategies for liquid chromatography remain the most attractive and practical route for increasing the number of spatially resolved components in order to reduce stress on necessary mass spectrometric detection. However, the stress placed on a chromatographic separation step as a second dimension in a comprehensive online methodology (i.e. online LC*LC) is rather high. As an alternative to online LC*LC combinations, coupling of HPLC with ion mobility spectrometry hyphenated to mass spectrometry (IMS-MS) has emerged as an attractive approach to permit comprehensive sampling of first dimension chromatographic peaks and subsequent introduction to an orthogonal IMS separation prior to measurement of ions by a mass spectrometer. In the present work, utilization of classical peak capacity and ion mobility theory allows theoretical assessment of the potential of two- (LC*IMS-MS) or even three dimensional (LC*LC*IMS-MS) experimental setups to enhance peak capacity and, therefore, the number of correctly annotated features within the framework of complex, non-targeted analysis problems frequently addressed using HPLC-MS strategies. Theoretical calculations indicate that newly-available drift tube IMS MS instrumentation can yield peak capacities of between 10 and 40 using nitrogen drift gas for typical non-targeted metabolomic, lipidomic and proteomic applications according to the expected reduced mobilities of components in the respective samples. Theoretically, this approach can significantly improve the overall peak capacity of conventional HPLC-(MS) methodologies to in excess of 10(4) depending upon the column length and gradient time employed. A more elaborate combination of LC*LC*IMS-MS would improve the ion suppression limitation and possibly allow access to theoretically even higher peak capacities, but such a combination may render the IMS separation practically redundant as well as imparting the well-known dilution problems associated with LC*LC. Finally, some predictions for the separation of co-eluted isobaric compounds can also be made by considering the required peak-to-peak resolution for acceptable IMS separation. The here-described theoretical predication approach can be used to aid method development for HPLC*IMS-MS and is also accompanied by some practical considerations that should be contemplated in associated non-targeted analysis workflows. PMID- 26372448 TI - No association between ApoE and schizophrenia: Evidence of systematic review and updated meta-analysis. AB - INTRODUCTION: Schizophrenia affects between 0.3% and 2% of the worldwide population. A genetic contribution has been postulated in the development of this disorder. Genes such as ApoE have been implicated in the neurodevelopment associated with schizophrenia in case-control and meta-analysis studies, but the results remain inconclusive. Due to this, the aim of the present study was to explore the association between ApoE and schizophrenia through a meta-analysis. MATERIAL AND METHODS: We collected all relevant studies by searching PubMed and EBSCO databases. The pooled odds ratios with 95% confidence intervals were calculated to estimate the association. The following models were evaluated: A) epsilon4 vs epsilon3, B) epsilon4 vs epsilon2, C) epsilon4 vs epsilon3+epsilon2, D) Caucasian population and E) Asian population. Statistical analyses were performed using EPIDAT 3.1 software. RESULTS: The meta-analyses comprised 28 association studies, which included 4703 controls and 3452 subjects with schizophrenia. A significant protective effect was found for allele epsilon3 in the Asian population (OR=0.73, 95% CI=0.54-0.98). No significant associations were observed in the other models and populations analyzed. CONCLUSIONS: Our meta analysis suggests a protective association between ApoE allele epsilon3 and schizophrenia in the Asian population. PMID- 26372449 TI - Lifestyle-Related Factors and Atopy in Seven Danish Population-Based Studies from Different Time Periods. AB - BACKGROUND: The prevalence of allergic respiratory disease tends to increase in populations that adopt the so-called Westernized lifestyle. We investigated the association between atopy and several possible lifestyle-related factors in seven Danish population-based studies. METHODS: A total of 20048 persons participated in the seven studies. We used logistic regression to analyse the associations between possible determinants and atopy defined as serum specific IgE or skin prick test positivity against inhalant allergens. Associations were expressed as odds ratios (ORs) with 95% confidence intervals (95% CIs). In addition, individual participant data meta-analyses were performed. RESULTS: Atopy was significantly associated with younger age (OR per 1 year increase in age: 0.97; 95% CI: 0.97, 0.98); male sex (OR for males versus females: 1.34; 95% CI: 1.24, 1.45), heavy drinking (OR for heavy drinkers versus light drinkers: 1.15; 95% CI: 1.04, 1.27), never smoking (OR for current versus never smokers: 0.73; 95% CI: 0.67, 0.80), and higher educational level (OR for educated versus uneducated: 1.27; 95% CI: 1.15, 1.41). Atopy was not associated with blood pressure, serum total cholesterol, physical activity or body mass except in women only, where we found a positive association (OR for obese vs. normal weight: 1.18; 95% CI: 1.00, 1.39) with ptrend = 0.032. CONCLUSIONS: Of interest for preventive purposes, we found that atopy was associated with some of the reversible lifestyle-related factors that characterize a Westernized lifestyle. PMID- 26372451 TI - Five-year Antibody Persistence and Safety After a Single Dose of Combined Haemophilus influenzae Type B Neisseria meningitidis Serogroup C-Tetanus Toxoid Conjugate Vaccine in Haemophilus influenzae Type B-primed Toddlers. AB - BACKGROUND: Antibody persistence is evaluated in healthy Australian children 4 and 5 years postvaccination with a single dose of combined Haemophilus influenzae type b-Neisseria meningitidis serogroup C tetanus toxoid conjugate vaccine (Hib MenC-TT) compared with separately administered Hib-TT and MenC-CRM197 vaccines (Hib + MCC). METHODS: This is another follow-up of a phase III, open, randomized, controlled study (NCT00326118), in which 433 Hib-primed but MenC naive toddlers aged 12-18 months were randomized 3:1 to receive Hib-MenC-TT or Hib + MCC vaccines. Protection against (1) MenC was measured by serum bactericidal antibody assay using rabbit complement (rSBA) and (2) Hib was measured by enzyme-linked immunosorbent assay of antibodies to polyribosylribitol phosphate (anti-PRP). Study children were assessed for any potentially vaccine-related serious adverse events at each persistence study visit. RESULTS: The according-to-protocol cohorts for persistence at years 4 and 5 included 282 and 263 children, respectively. The percentages of children with rSBA-MenC titers >=1:8 at years 4 and 5 were 12.5% and 19.0%, respectively, in the Hib-MenC group; and 12.3% and 25.0% in the Hib + MCC group. All children in each group had anti-PRP concentrations >=0.15 MUg/mL at year 5. Exploratory analyses suggested no potential differences between groups in rSBA-MenC or anti-PRP antibody persistence. No vaccine-related serious adverse events were reported. CONCLUSIONS: Antibody persistence was similar for years 4 and 5 after Hib-MenC-TT or Hib + MCC vaccination, with the majority of children retaining anti-PRP antibody concentrations >=0.15 MUg/mL at both timepoints. The percentage of children retaining rSBA-MenC titers >=1:8 was low (<=25%), suggesting that a MenC booster dose may be warranted before adolescence. PMID- 26372450 TI - Human Metapneumovirus Infection in Jordanian Children: Epidemiology and Risk Factors for Severe Disease. AB - BACKGROUND: Human metapneumovirus (HMPV) is a leading cause of acute respiratory tract infection in young children. Our objectives were to define HMPV epidemiology and circulating strains and determine markers of severe disease in Jordanian children. METHODS: We conducted a prospective study from March 16, 2010 to March 31, 2013 using quantitative reverse transcription-polymerase chain reaction to determine the frequency of HMPV infection among children <2 years old admitted with fever and/or acute respiratory illness to a major government hospital in Amman, Jordan. RESULTS: HMPV was present in 273 of 3168 (8.6%) of children presenting with acute respiratory tract infection. HMPV A2, B1 and B2, but not A1, were detected during the 3-year period. HMPV-infected children were older and more likely to be diagnosed with bronchopneumonia than HMPV-negative children. HMPV-infected children with lower respiratory tract infection had higher rates of cough and shortness of breath than children with lower respiratory tract infection infected with other or no identifiable viruses. Symptoms and severity were not different between children with HMPV only compared with HMPV coinfection. Children with HMPV subgroup A infection were more likely to require supplemental oxygen. In a multivariate analysis, HMPV subgroup A and age <6 months were independently associated with supplemental oxygen requirement. CONCLUSIONS: HMPV is a leading cause of acute respiratory tract disease in Jordanian children <2 years old. HMPV A and young age were associated with severe disease. Ninety percent of HMPV-infected hospitalized children were full term and otherwise healthy, in contrast to high-income nations; thus, factors contributing to disease severity likely vary depending on geographic and resource differences. PMID- 26372452 TI - Epidemiologic Features of Kawasaki Disease in Shanghai From 2008 Through 2012. AB - BACKGROUND: This study was to investigate the epidemiologic trends of Kawasaki disease (KD) and coronary arterial lesions (CALs) in Shanghai from 2008 through 2012. METHODS: Data were collected by using the network of the KD research group established during the first survey in Shanghai to conduct the third survey, covering the period from 2008 through 2012. Clinical records of 2304 patients with acute KD were retrospectively reviewed. Epidemiologic features of KD were investigated. Univariate and multivariate analyses were performed to identify the risk factors for CAL in patients with KD. The data were compared with the previous 2 surveys covering the periods from 1998 to 2002 and 2003 to 2007, respectively. RESULTS: The average incidence of KD was 30.3 to 71.9 per 100,000 children aged 0-4 years from 2008 through 2012. Age at onset ranged from 32 days to 11.7 years (median: 2.3 years). The occurrence of KD was more common in summer and spring. A total of 365 (15.9%) cases developed CAL defined as ectasia or aneurysm. Male, age <= 1 year, intravenous immunoglobulin (IVIG) unresponsiveness, a smaller administrative dosage and the delayed administration of IVIG (>10 days) were independent risk factors for CAL. The occurrence of CAL seemed less frequent in patients who received IVIG within 5 days after onset of illness. CONCLUSIONS: The incidence of KD in children has increased over time, and the development of CAL decreased in the past 5 years in Shanghai. Earlier treatment with IVIG (<5 days) was associated with reduced CAL among patients with KD. PMID- 26372453 TI - Decreased Mitochondrial Function Among Healthy Infants Exposed to Antiretrovirals During Gestation, Delivery and the Neonatal Period. AB - BACKGROUND: Antiretroviral (ARV)-associated mitochondrial toxicity in HIV/ARV exposed healthy infants is a concern. Clinically relevant toxicity is rare. Hyperlactatemia is common but nonspecific, both increased and decreased mitochondrial DNA (mtDNA) level has been reported. Mitochondrial function has scarcely been investigated. METHODS: In a prospective observational study of 133 HIV/ARV-exposed infants, mtDNA content was measured with quantitative real-time polymerase chain reaction, and mitochondrial respiratory chain enzymatic activity of complex IV (CIV) and mitochondrial mass (MM) were assessed spectrophotometrically from cryopreserved peripheral blood mononuclear cells obtained at 6 weeks and 3, 6 and 12 months of age and compared with a control group. RESULTS: Most mothers (88%) received combined ARV therapy during pregnancy, and 92% of infants received zidovudine monotherapy. No infant had clinical evidence of mitochondrial disease during follow-up. Nonsignificant higher MM and lower mtDNA levels (normalized by MM) were observed over time in HIV/ARV-exposed infants. MM-normalized CIV activity was consistently lower in HIV/ARV-exposed children than in controls over time (0.09 vs. 0.35, 0.12 vs. 0.38, 0.13 vs. 0.24 and 0.14 vs. 0.24 nmol/min/mg at 6 weeks and 3, 6 and 12 months; P = 0.014, P < 0.0001, P = 0.065 and P = 0.011, respectively) and showed a linear trend toward normalization with age (P < 0.01). In HIV/ARV-exposed infants, an inverse correlation between CIV activity and mtDNA levels was observed until 6 months of age (r = -0.327, P = 0.016; r = -0.311, P = 0.040 and r = -0.275, P = 0.046). CONCLUSIONS: Mitochondrial-encoded CIV activity was consistently lower among HIV/ARV-exposed healthy infants and inversely correlated with mtDNA levels, suggesting upregulation of the latter. PMID- 26372454 TI - Intraspecific Colour Variation among Lizards in Distinct Island Environments Enhances Local Camouflage. AB - Within-species colour variation is widespread among animals. Understanding how this arises can elucidate evolutionary mechanisms, such as those underlying reproductive isolation and speciation. Here, we investigated whether five island populations of Aegean wall lizards (Podarcis erhardii) have more effective camouflage against their own (local) island substrates than against other (non local) island substrates to avian predators, and whether this was linked to island differences in substrate appearance. We also investigated whether degree of local substrate matching varied among island populations and between sexes. In most populations, both sexes were better matched against local backgrounds than against non-local backgrounds, particularly in terms of luminance (perceived lightness), which usually occurred when local and non-local backgrounds were different in appearance. This was found even between island populations that historically had a land connection and in populations that have been isolated relatively recently, suggesting that isolation in these distinct island environments has been sufficient to cause enhanced local background matching, sometimes on a rapid evolutionary time-scale. However, heightened local matching was poorer in populations inhabiting more variable and unstable environments with a prolonged history of volcanic activity. Overall, these results show that lizard coloration is tuned to provide camouflage in local environments, either due to genetic adaptation or changes during development. Yet, the occurrence and extent of selection for local matching may depend on specific conditions associated with local ecology and biogeographic history. These results emphasize how anti predator adaptations to different environments can drive divergence within a species, which may contribute to reproductive isolation among populations and lead to ecological speciation. PMID- 26372455 TI - Differential amniotic fluid cytokine profile in women with chorioamnionitis with and without funisitis. AB - OBJECTIVES: To evaluate whether the amniotic fluid (AF) cytokine profile in women with chorioamnionitis may differentiate between those with and without funisitis. SUBJECTS AND METHODS: Forty women at high risk of chorioamnionitis were studied. Gestational age at study was 26.94. Amniocentesis, universal and specific polymerase chain reaction, and microbiological cultures were performed. AF IL 1beta, IL-2, IL-4, IL-6, IL 8, IL-10, IL-12, TNF-alpha, IFN-gamma, and MMP-8 were measured by multiplex assay. After delivery, the placenta and umbilical cord were studied histologically. Comparisons were made between three groups: controls, and chorioamnionitis with and without funisitis. RESULTS: In 25 cases, the histological findings were normal (61.5%). The remaining 15 composed of 9 cases of chorioamnionitis alone (9/40; 23.1%) and 6 cases of chorioamnionitis plus funisitis (6/40; 15.4%). All AF cytokine levels were significantly higher in the cases with chorioamnionitis in comparison to controls, except for IFN-gamma. The comparisons between the three groups showed significant differences between chorioamnionitis alone and chorioamnionitis plus funisitis in IL-1beta, IL-6, IL 10, IL-12, IL-8, and TNF-alpha, with the levels being higher when funisitis was present. Logistic regression found a powerful predictive model for funisitis including the following cytokinesIL-4, IL-10, IL-12, and IL-8. CONCLUSIONS: Measurements of AF interleukins 4, 10, 12, and 8 allow to identify cases with funisitisin women at high risk of chorioamnionitis. PMID- 26372456 TI - Roles of Klf5 Acetylation in the Self-Renewal and the Differentiation of Mouse Embryonic Stem Cells. AB - Transcription factor Kruppel-like factor 5 (Klf5) plays important roles in the formation of the inner cell mass (ICM) and the trophectoderm during embryogenesis, as well as the self-renewal and the differentiation of mouse embryonic stem cells (ESCs). Acetylation of KLF5 has been shown to reverse the transcriptional activity of KLF5 in human epidermal cells and prostate cancer cells. Whether Klf5 acetylation contributes to the lineage specification in the blastocyst and pluripotency maintenance in ESCs remains unexplored. Here, we showed the ubiquitous expression of acetylated Klf5 in the ICM and the trophectoderm, ruling out the possibility that differential acetylation status of Klf5 leads to the lineage specification in the blastocyst. We found that K358Q mutation, mimicking acetylation, enhances the transcriptional activity of Klf5 for pluripotency genes in ESCs, and that K358Q Klf5 is more potent in pluripotency maintenance and in somatic cell reprogramming, compared to K358R Klf5. In ESCs, Klf5 acetylation, stimulated by TGF-beta signaling, is involved in enhancing Sox2 expression. Moreover, upon ESC differentiation, acetylation of Klf5 facilitates the suppression of many differentiation genes, except for that K358Q Klf5 activates Cdx2, promoting trophectodermal differentiation. In summary, our results revealed the regulatory functions of Klf5 acetylation in ESC self renewal and differentiation. PMID- 26372457 TI - [Persistent left superior vena cava: Clinical significance]. PMID- 26372458 TI - Bond Strength of Resin Cements to Zirconia Ceramic Using Adhesive Primers. AB - PURPOSE: To evaluate the influence of adhesive primers on the microshear bond strength of resin cements to zirconia ceramic. MATERIALS AND METHODS: Fifty zirconia plates (12 mm * 5 mm * 1.5 mm thick) of a commercially available zirconium oxide ceramic (ZirCad) were sintered, sandblasted with aluminum oxide particles, and cleaned ultrasonically before bonding. The plates were randomly divided into five groups of 10. Three resin cements were selected (RelyX ARC, Multilink Automix, Clearfil SA Cement self-adhesive resin cement), along with two primers (Metal-Zirconia Primer, Alloy Primer) and one control group. The primers and resin cements were used according to manufacturers' recommendations. The control group comprised the conventional resin cement (RelyX ARC) without adhesive primer. Test cylinders (0.75 mm diameter * 1 mm high) were formed on zirconia surfaces by filling cylindrical Tygon tube molds with resin cement. The specimens were stored in distilled water for 24 hours at 37 degrees C, then tested for shear strength on a Shimadzu EZ Test testing machine at 0.5 mm/min. Bond strength data were analyzed statistically by two-way ANOVA and Dunnett's test (5%). RESULTS: The bond strength means in MPa (+/- s.d.) were: RelyX ARC: 28.1 (6.6); Multilink Automix: 37.6 (4.5); Multilink Automix + Metal-Zirconia Primer: 55.7 (4.0); Clearfil SA Cement: 46.2 (3.3); and Clearfil SA Cement + Alloy Primer: 47.0 (4.1). CONCLUSION: Metal-Zirconia Primer increased the bond strength of Multilink Automix resin cement to zirconia, but no effect was observed for Alloy Primer using Clearfil SA Cement. RelyX ARC showed the lowest bond strength to zirconia. PMID- 26372460 TI - Changing nomenclature for PBC: From 'cirrhosis' to 'cholangitis'. PMID- 26372459 TI - Sexual health in hematopoietic stem cell transplant recipients. AB - Hematopoietic stem cell transplantation (HSCT) plays a central role in patients with malignant and, increasingly, nonmalignant conditions. As the number of transplants increases and the survival rate improves, long-term complications are important to recognize and treat to maintain quality of life. Sexual dysfunction is a commonly described but relatively often underestimated complication after HSCT. Conditioning regimens, generalized or genital graft-versus-host disease, medications, and cardiovascular complications as well as psychosocial problems are known to contribute significantly to physical and psychological sexual dysfunction. Moreover, it is often a difficult topic for patients, their significant others, and health care providers to discuss. Early recognition and management of sexual dysfunction after HSCT can lead to improved quality of life and outcomes for patients and their partners. This review focuses on the risk factors for and treatment of sexual dysfunction after transplantation and provides guidance concerning how to approach and manage a patient with sexual dysfunction after HSCT. PMID- 26372461 TI - Primary Somatosensory Cortices Contain Altered Patterns of Regional Cerebral Blood Flow in the Interictal Phase of Migraine. AB - The regulation of cerebral blood flow (CBF) is a complex integrated process that is critical for supporting healthy brain function. Studies have demonstrated a high incidence of alterations in CBF in patients suffering from migraine with and without aura during different phases of attacks. However, the CBF data collected interictally has failed to show any distinguishing features or clues as to the underlying pathophysiology of the disease. In this study we used the magnetic resonance imaging (MRI) technique-arterial spin labeling (ASL)-to non-invasively and quantitatively measure regional CBF (rCBF) in a case-controlled study of interictal migraine. We examined both the regional and global CBF differences between the groups, and found a significant increase in rCBF in the primary somatosensory cortex (S1) of migraine patients. The CBF values in S1 were positively correlated with the headache attack frequency, but were unrelated to the duration of illness or age of the patients. Additionally, 82% of patients reported skin hypersensitivity (cutaneous allodynia) during migraine, suggesting atypical processing of somatosensory stimuli. Our results demonstrate the presence of a disease-specific functional deficit in a known region of the trigemino-cortical pathway, which may be driven by adaptive or maladaptive functional plasticity. These findings may in part explain the altered sensory experiences reported between migraine attacks. PMID- 26372462 TI - Speciation without Pre-Defined Fitness Functions. AB - The forces promoting and constraining speciation are often studied in theoretical models because the process is hard to observe, replicate, and manipulate in real organisms. Most models analyzed to date include pre-defined functions influencing fitness, leaving open the question of how speciation might proceed without these built-in determinants. To consider the process of speciation without pre-defined functions, we employ the individual-based ecosystem simulation platform EcoSim. The environment is initially uniform across space, and an evolving behavioural model then determines how prey consume resources and how predators consume prey. Simulations including natural selection (i.e., an evolving behavioural model that influences survival and reproduction) frequently led to strong and distinct phenotypic/genotypic clusters between which hybridization was low. This speciation was the result of divergence between spatially-localized clusters in the behavioural model, an emergent property of evolving ecological interactions. By contrast, simulations without natural selection (i.e., behavioural model turned off) but with spatial isolation (i.e., limited dispersal) produced weaker and overlapping clusters. Simulations without natural selection or spatial isolation (i.e., behaviour model turned off and high dispersal) did not generate clusters. These results confirm the role of natural selection in speciation by showing its importance even in the absence of pre-defined fitness functions. PMID- 26372463 TI - Correction: Activity-Based Proteomic Profiling of Deubiquitinating Enzymes in Salmonella-Infected Macrophages Leads to Identification of Putative Function of UCH-L5 in Inflammasome Regulation. PMID- 26372466 TI - The ELLIPTA(r) Dry Powder Inhaler: Design, Functionality, In Vitro Dosing Performance and Critical Task Compliance by Patients and Caregivers. AB - Dry powder inhalers (DPIs) are commonly used for the delivery of inhaled medications, and should provide consistent, efficient dosing, be easy to use correctly, and be liked by patients; these attributes can all affect patient compliance and therefore treatment efficacy. The ELLIPTA((r)) DPI was developed for the delivery of once-daily therapies for the treatment of asthma and chronic obstructive pulmonary disease. It has moderate resistance to airflow and can hold one or two blister strips, with each blister containing a sealed single dose of medication. Monotherapies can be delivered by the single-strip configuration and, in the two-strip configuration, one dose from each strip can be aerosolized simultaneously to allow combination therapies to be delivered, which enables the formulations for each product to be developed individually, since they are stored separately until the point of administration. There are three principal operating steps to administer a dose: open, inhale, close. This article summarizes the design, functionality, and in vitro dose-delivery characteristics of the ELLIPTA inhaler, and describes the results of human factors validation tests, designed to assess the performance of critical tasks required to use the inhaler. Results from the in vitro studies indicate that the ELLIPTA inhaler performs consistently with respect to in vitro dose delivery characteristics at a range of flow rates that can be achieved by the target population (>=30 L/min) and over its 30-day in use life. Data from the human factors validation tests demonstrated that almost all participants (>=97%) were able to complete each of the steps required to prepare a dose for inhalation without error. Overall, the ELLIPTA inhaler has a versatile single- or two-strip design that allows it to be used for the delivery of a range of treatment options. It also improves patient ease-of-use when compared with the DISKUS((r)) DPI. PMID- 26372465 TI - In Vitro Dosing Performance of the ELLIPTA(r) Dry Powder Inhaler Using Asthma and COPD Patient Inhalation Profiles Replicated with the Electronic Lung (eLungTM). AB - BACKGROUND: To evaluate the in vitro dose delivery characteristics of approved asthma and chronic obstructive pulmonary disease (COPD) therapies delivered via the ELLIPTA((r)) dry powder inhaler across inhalation endpoints representative of the target patient population, using the Electronic Lung (eLungTM) to replicate inhaler-specific patient inhalation profiles that were previously recorded in vivo. METHODS: Selected profiles, representative of the range of inhalation endpoints achieved by patients with all severities of asthma and COPD, were replicated using the eLung breathing simulator in conjunction with an oropharyngeal cast. A Next Generation Impactor was coupled to the eLung to determine the aerodynamic particle size distribution of the ex-throat dose (ETD) of asthma and COPD therapies delivered via the ELLIPTA inhaler. Delivered dose (DD), ETD, and fine particle dose (FPD; defined as a mass of active substance less than 5 MUm) were determined for fluticasone furoate (FF)/vilanterol (VI) 100/25 MUg and 200/25 MUg (asthma and COPD), umeclidinium (UMEC)/VI 62.5/25 MUg (COPD only), FF 100 MUg and 200MUg monotherapy (asthma only), and UMEC 62.5 MUg monotherapy (COPD only). RESULTS: Inhalation profiles replicated by eLung covered a wide range of peak inspiratory flow rates (41.6-136.9 L/min), pressure drops (1.2-13.8 kPa), and inhaled volumes through the inhaler (0.7-4.2L). DD was consistent across the range of patient representative inhalation parameters for all components (FF, VI, and UMEC) of each therapy assessed; although ETD and FPD were also generally consistent, some small variation was observed. Dose delivery was consistent for each of the components, whether delivered as mono- or combination therapy. CONCLUSIONS: The in vitro performance of the ELLIPTA inhaler has been demonstrated for the delivery of FF/VI, UMEC/VI, FF monotherapy, and UMEC monotherapy. Across a range of inspiratory profiles, DD was consistent, while ETD and FPD showed little flow dependency. PMID- 26372467 TI - Effect of Disease Severity in Asthma and Chronic Obstructive Pulmonary Disease on Inhaler-Specific Inhalation Profiles Through the ELLIPTA(r) Dry Powder Inhaler. AB - BACKGROUND: Two studies were undertaken to characterize the maximal effort inhalation profiles of healthy subjects and patients with asthma or chronic obstructive pulmonary disease (COPD) through a moderate-resistance dry powder inhaler (DPI). Correlations between inhaler-specific inhalation characteristics and inhaler-independent lung function parameters were investigated. METHODS: Healthy subjects (n = 15), patients with mild, moderate, or severe asthma (n = 45), and patients with mild, moderate, severe, or very-severe COPD (n = 60) were included in the studies. Inhalation pressure drop versus time profiles were recorded using an instrumented ELLIPTA(r) DPI or bespoke resistor component with equivalent resistivity. Inhaler-independent lung function assessments included pharyngometry, spirometry, plethysmography, and diffusion. RESULTS: For the inhaler-specific inhalation profiles, the mean maximal effort peak inspiratory flow rates (PIFRs) varied across the subgroups from 65.8-110.6 L/min (range: 41.6 142.9). Peak pressure drop, PIFR, inhaled volume, and average inhalation flow rate (primary endpoints) did not differ markedly between healthy subjects and patients with asthma or mild COPD. Moderate, severe, and very-severe COPD patients demonstrated lower mean peak pressure drops, PIFRs and inhaled volumes, which tended to decrease with increasing COPD severity. Severe and very-severe COPD patients demonstrated shorter mean inhalation times compared with all other participants. Inhaler-independent lung function parameters were consistent with disease severity, and statistically significant (p < 0.05) strong correlations (R > 0.7) with components of the inhaler-specific inhalation profiles were observed in the COPD cohort; correlations in the asthma cohort tended to be weaker. CONCLUSIONS: All participants achieved a maximal effort PIFR >= 41.6 L/min through the moderate resistance of the ELLIPTA inhaler. Patients with asthma achieved similar inhalation profiles to healthy subjects, but increasing COPD severity tended to reduce a patient's inhalation capability. Correlation analyses suggest that some lung function parameters may be a useful indicator of ability to inhale efficiently through a moderate-resistance DPI, such as the ELLIPTA inhaler. PMID- 26372469 TI - Multistep Kinetic Behavior of the Thermal Decomposition of Granular Sodium Percarbonate: Hindrance Effect of the Outer Surface Layer. AB - The kinetics and mechanism of the thermal decomposition of granular sodium percarbonate (SPC), which is used as a household oxygen bleach, were studied by thermoanalytical measurements under systematically changing conditions and morphological observation of the reactant solids at different reaction stages. A physico-geometrical kinetic behavior of the reaction that occurs in a core-shell structure composed of an outer surface layer and internal aggregates of SPC crystalline particles was illustrated through detailed kinetic analyses using the kinetic deconvolution method. Simultaneously, the hazardous nature of SPC as a combustion improver was evaluated on the basis of the kinetic behavior of the thermal decomposition. It was found that the outer surface layers of the SPC granules hinder the diffusional removal of product gases generated by the thermal decomposition of the internal SPC crystalline particles. The reaction rate decelerates because of an increase in the internal gaseous pressure as the reaction advances. However, the reaction rate accelerates once crack formation occurs in the outer surface layer at the midpoint of the reaction. Therefore, the overall reaction was empirically demonstrated to consist of two overlapping reaction steps owing to the changes in the self-generated reaction conditions in the interior of the SPC granules. PMID- 26372468 TI - Androgen Receptor-Mediated Growth Suppression of HPr-1AR and PC3-Lenti-AR Prostate Epithelial Cells. AB - The androgen receptor (AR) mediates the developmental, physiologic, and pathologic effects of androgens including 5alpha-dihydrotestosterone (DHT). However, the mechanisms whereby AR regulates growth suppression and differentiation of luminal epithelial cells in the prostate gland and proliferation of malignant versions of these cells are not well understood, though they are central to prostate development, homeostasis, and neoplasia. Here, we identify androgen-responsive genes that restrain cell cycle progression and proliferation of human prostate epithelial cell lines (HPr-1AR and PC3-Lenti AR), and we investigate the mechanisms through which AR regulates their expression. DHT inhibited proliferation of HPr-1AR and PC3-Lenti-AR, and cell cycle analysis revealed a prolonged G1 interval. In the cell cycle, the G1/S phase transition is initiated by the activity of cyclin D and cyclin-dependent kinase (CDK) complexes, which relieve growth suppression. In HPr-1AR, cyclin D1/2 and CDK4/6 mRNAs were androgen-repressed, whereas CDK inhibitor, CDKN1A, mRNA was androgen-induced. The regulation of these transcripts was AR-dependent, and involved multiple mechanisms. Similar AR-mediated down-regulation of CDK4/6 mRNAs and up-regulation of CDKN1A mRNA occurred in PC3-Lenti-AR. Further, CDK4/6 overexpression suppressed DHT-inhibited cell cycle progression and proliferation of HPr-1AR and PC3-Lenti-AR, whereas CDKN1A overexpression induced cell cycle arrest. We therefore propose that AR-mediated growth suppression of HPr-1AR involves cyclin D1 mRNA decay, transcriptional repression of cyclin D2 and CDK4/6, and transcriptional activation of CDKN1A, which serve to decrease CDK4/6 activity. AR-mediated inhibition of PC3-Lenti-AR proliferation occurs through a similar mechanism, albeit without down-regulation of cyclin D. Our findings provide insight into AR-mediated regulation of prostate epithelial cell proliferation. PMID- 26372472 TI - Defect engineering as a versatile route to estimate various scattering mechanisms in monolayer graphene on solid substrates. AB - It is known that the experimental conditions and growth methods determine the different carrier scatterings responsible for large variation of carrier mobility in graphene monolayers. Here we present a systematic investigation on various possible scattering mechanisms responsible for limiting the carrier mobility in graphene on a solid substrate, like SiO2. This has been possible by defect engineering in graphene monolayers obtained by liquid phase exfoliation of graphite in polar and non-polar solvents with the dielectric constant varying from 2.5 to 64. Lattice defects in graphene monolayers have been characterized by scanning tunnelling microscopy and Raman spectroscopy. Correlation between the results obtained from electrical measurements and the information obtained from Raman spectra have revealed different scattering mechanisms responsible for deciding the carrier mobility. It has been shown that remote interfacial phonons in SiO2 are responsible for limiting the carrier mobility at room temperature whereas, substrate impurities and Raman active point defects in the graphene lattice are the dominant scatterers for limiting the mobility at low temperatures. PMID- 26372471 TI - Evidence for extensive parallelism but divergent genomic architecture of adaptation along altitudinal and latitudinal gradients in Populus trichocarpa. AB - Adaptation to climate across latitude and altitude reflects shared climatic constraints, which may lead to parallel adaptation. However, theory predicts that higher gene flow should favor more concentrated genomic architectures, which would lead to fewer locally maladapted recombinants. We used exome capture to resequence the gene space along a latitudinal and two altitudinal transects in the model tree Populus trichocapra. Adaptive trait phenotyping was coupled with FST outlier tests and sliding window analysis to assess the degree of parallel adaptation as well as the genomic distribution of outlier loci. Up to 51% of outlier loci overlapped between transect pairs and up to 15% of these loci overlapped among all three transects. Genomic clustering of adaptive loci was more pronounced for altitudinal than latitudinal transects. In both altitudinal transects, there was a larger number of these 'islands of divergence', which were on average longer and included several of exceptional physical length. Our results suggest that recapitulation of genetic clines over latitude and altitude involves extensive parallelism, but that steep altitudinal clines generate islands of divergence. This suggests that physical proximity of genes in coadapted complexes may buffer against the movement of maladapted alleles from geographically proximal but climatically distinct populations. PMID- 26372470 TI - Effectiveness of Electronic Reminders to Improve Medication Adherence in Tuberculosis Patients: A Cluster-Randomised Trial. AB - BACKGROUND: Mobile text messaging and medication monitors (medication monitor boxes) have the potential to improve adherence to tuberculosis (TB) treatment and reduce the need for directly observed treatment (DOT), but to our knowledge they have not been properly evaluated in TB patients. We assessed the effectiveness of text messaging and medication monitors to improve medication adherence in TB patients. METHODS AND FINDINGS: In a pragmatic cluster-randomised trial, 36 districts/counties (each with at least 300 active pulmonary TB patients registered in 2009) within the provinces of Heilongjiang, Jiangsu, Hunan, and Chongqing, China, were randomised using stratification and restriction to one of four case-management approaches in which patients received reminders via text messages, a medication monitor, combined, or neither (control). Patients in the intervention arms received reminders to take their drugs and reminders for monthly follow-up visits, and the managing doctor was recommended to switch patients with adherence problems to more intensive management or DOT. In all arms, patients took medications out of a medication monitor box, which recorded when the box was opened, but the box gave reminders only in the medication monitor and combined arms. Patients were followed up for 6 mo. The primary endpoint was the percentage of patient-months on TB treatment where at least 20% of doses were missed as measured by pill count and failure to open the medication monitor box. Secondary endpoints included additional adherence and standard treatment outcome measures. Interventions were not masked to study staff and patients. From 1 June 2011 to 7 March 2012, 4,292 new pulmonary TB patients were enrolled across the 36 clusters. A total of 119 patients (by arm: 33 control, 33 text messaging, 23 medication monitor, 30 combined) withdrew from the study in the first month because they were reassessed as not having TB by their managing doctor (61 patients) or were switched to a different treatment model because of hospitalisation or travel (58 patients), leaving 4,173 TB patients (by arm: 1,104 control, 1,008 text messaging, 997 medication monitor, 1,064 combined). The cluster geometric mean of the percentage of patient-months on TB treatment where at least 20% of doses were missed was 29.9% in the control arm; in comparison, this percentage was 27.3% in the text messaging arm (adjusted mean ratio [aMR] 0.94, 95% CI 0.71, 1.24), 17.0% in the medication monitor arm (aMR 0.58, 95% CI 0.42, 0.79), and 13.9% in the combined arm (aMR 0.49, 95% CI 0.27, 0.88). Patient loss to follow-up was lower in the text messaging arm than the control arm (aMR 0.42, 95% CI 0.18-0.98). Equipment malfunction or operation error was reported in all study arms. Analyses separating patients with and without medication monitor problems did not change the results. Initiation of intensive management was underutilised. CONCLUSIONS: This study is the first to our knowledge to utilise a randomised trial design to demonstrate the effectiveness of a medication monitor to improve medication adherence in TB patients. Reminders from medication monitors improved medication adherence in TB patients, but text messaging reminders did not. In a setting such as China where universal use of DOT is not feasible, innovative approaches to support patients in adhering to TB treatment, such as this, are needed. TRIAL REGISTRATION: Current Controlled Trials, ISRCTN46846388. PMID- 26372473 TI - Three-Dimensional Mapping of Soil Chemical Characteristics at Micrometric Scale by Combining 2D SEM-EDX Data and 3D X-Ray CT Images. AB - There is currently a significant need to improve our understanding of the factors that control a number of critical soil processes by integrating physical, chemical and biological measurements on soils at microscopic scales to help produce 3D maps of the related properties. Because of technological limitations, most chemical and biological measurements can be carried out only on exposed soil surfaces or 2-dimensional cuts through soil samples. Methods need to be developed to produce 3D maps of soil properties based on spatial sequences of 2D maps. In this general context, the objective of the research described here was to develop a method to generate 3D maps of soil chemical properties at the microscale by combining 2D SEM-EDX data with 3D X-ray computed tomography images. A statistical approach using the regression tree method and ordinary kriging applied to the residuals was developed and applied to predict the 3D spatial distribution of carbon, silicon, iron, and oxygen at the microscale. The spatial correlation between the X-ray grayscale intensities and the chemical maps made it possible to use a regression-tree model as an initial step to predict the 3D chemical composition. For chemical elements, e.g., iron, that are sparsely distributed in a soil sample, the regression-tree model provides a good prediction, explaining as much as 90% of the variability in some of the data. However, for chemical elements that are more homogenously distributed, such as carbon, silicon, or oxygen, the additional kriging of the regression tree residuals improved significantly the prediction with an increase in the R2 value from 0.221 to 0.324 for carbon, 0.312 to 0.423 for silicon, and 0.218 to 0.374 for oxygen, respectively. The present research develops for the first time an integrated experimental and theoretical framework, which combines geostatistical methods with imaging techniques to unveil the 3-D chemical structure of soil at very fine scales. The methodology presented in this study can be easily adapted and applied to other types of data such as bacterial or fungal population densities for the 3D characterization of microbial distribution. PMID- 26372474 TI - How to perform transabdominal chorionic villus sampling: a practical guideline. AB - The spread of both first trimester screening for chromosomal abnormalities and the possibility to check for single gene disorders at DNA-analysis has increased the request for chorionic villus sampling (CVS) in the first trimester. In order to perform placental biopsy, two routes are possible: the transcervical (TC) and the transabdominal (TA). In early days, the trancervical technique was the most diffused, but since its introduction into clinical practice, the TA technique has become the approach of choice in detriment of the TC technique. In our institution, we have a 30-year experience in TA-CVS with more than 26 000 procedures performed. Considering the expertise and the volume of procedures undertaken at our unit, we suggest a practical guideline for novel operators in TA-CVS. PMID- 26372475 TI - Anterior Chamber Angle and Anterior Chamber Volume in a 40- to 64-Year-Old Population. AB - PURPOSE: To determine the distribution of the anterior chamber angle (ACA) and anterior chamber volume (ACV) in an Iranian population of 40- to 64-year-old people using the Pentacam. METHODS: In this cross-sectional study, multistage sampling was used to select 300 clusters, including 6,311 individuals from the city of Shahroud. All selected participants underwent examinations in one place. Optometric examinations, including measurement of visual acuity and refraction, and ophthalmologic examinations, including slit-lamp examination, were performed for all participants. Moreover, all patients underwent imaging with the Pentacam. RESULTS: The mean ACA and ACV was 34.3 degrees (95% confidence interval [CI]: 34.1 degrees -34.5 degrees ) and 139 MUL (95% CI: 137.7-140.3), respectively. In a multiple linear regression model, the ACA was inversely correlated with age (coefficient=-0.08), lens thickness (coefficient=-1.38), corneal diameter (coefficient=-0.36), and corneal curvature (coefficient=-1.43), and directly correlated with the anterior chamber depth (ACD) (coefficient=6.59). In another model, ACV was inversely correlated with age (coefficient=-0.37), central corneal thickness (coefficient=-0.04), and spherical equivalent (coefficient=-1.15), and directly correlated with the ACD (coefficient=85.67), lens thickness (coefficient=14.15), corneal diameter (coefficient=4.80), corneal curvature (coefficient=18.43), ACA (coefficient=0.65), and intraocular pressure (coefficient=0.23). CONCLUSION: The findings of this study could be used as a reference for diagnosis and treatment in Iran and the Middle East region. Increase in age and decrease in the ACD were important factors associated with decreased ACA and ACV, although the correlation of other biometric components was also evaluated. Some of these components, such as the corneal curvature and lens thickness, had a significant relationship with these two variables. PMID- 26372476 TI - Dry Eye Treatment Based on Contact Lens Drug Delivery: A Review. AB - Dry eye disease affects a substantial segment of the word population with increasing frequency. It is a multifactorial disease of the ocular surface and tear film, which causes ocular discomfort, visual disturbances, and tear instability with potential damage to the cornea and conjunctiva. Because of its multifactorial etiology, the use of different pharmacological treatment for dry eye treatment has been proposed, which include anti-inflammatory molecules, lubricants or comfort agents, and secretagogues. However, in some cases these pharmacological approaches only relieve symptoms temporarily, and consequently, eye care professionals continue to have difficulties managing dry eye. To improve pharmacological therapy that allows a more efficient and long-term action, effective ocular drug delivery of the currently available drugs for dry eye treatment is required. Contact lenses are emerging as alternative ophthalmic drugs delivery systems that provide an increased residence time of the drug at the eye, thus leading to enhanced bioavailability and more convenient and efficacious therapy. In this article, we reviewed the different techniques used to prepare contact lens-based drug delivery systems and focused on articles that describe the delivery of compounds for dry eye treatment through contact lenses. PMID- 26372477 TI - Open Globe Injuries Presenting With Normal or High Intraocular Pressure. AB - OBJECTIVES: To determine the frequency, clinical characteristics, and visual outcomes of patients who present with high or normal intraocular pressure (IOP) and open globe injuries. DESIGN: Retrospective chart review. SETTING: University of Maryland Medical Center, a level 1 trauma center. PATIENT OR STUDY POPULATION: All cases of open globe injury presenting to The University of Maryland Medical Center from July 2005 to January 2014. OBSERVATION: Demographics, initial physical examination, computed tomography findings, IOP of the affected and unaffected eyes, and follow-up evaluations. MAIN OUTCOME MEASURES: (1) IOP 10 mm Hg or greater and (2) visual acuity. RESULTS: Of 132 eyes presenting with open globe injury, IOP was recorded in 38 (28%). Mean IOP for the affected and unaffected eyes was 14+/-10.3 mm Hg and 16.6+/-4.1 mm Hg, respectively. Twenty three (59.4%) eyes had IOP greater than 10 mm Hg. Six eyes (16.2%) had IOP greater than 21 mm Hg. Using bivariate analysis, IOP greater than 10 mm Hg was associated with posterior open globe injury (P=0.01), posterior hemorrhage (P=0.04), and intraconal retrobulbar hemorrhage (P=0.05). Adjusting for age, sex, and race, IOP greater than 10 mm Hg was associated with the presence of posterior open globe injury on clinical examination (P=0.04). Higher presenting IOP was found to predict light perception or worse vision (P=0.01). Multivariate analysis showed that poor presenting vision was the best predictor of poor final vision (P<0.01). CONCLUSIONS: High IOP does not exclude open globe injury. It is a frequent finding in patients with open globe injuries and may be associated with posterior injury and poor visual prognosis. PMID- 26372479 TI - Effect of nondisclosure of HIV status in sexual health clinics on unlinked anonymous HIV prevalence estimates in England, 2005-2009. AB - OBJECTIVES: To assess the extent of nondisclosure of known HIV status among sexual health clinic attendees and to quantify the impact of nondisclosure on estimates of undiagnosed HIV prevalence and of the proportion of patients remaining undiagnosed on leaving the clinic. METHODS: Serum samples from the unlinked anonymous survey of clinic attendees' archive were tested for antiretrovirals. Estimates of undiagnosed HIV were adjusted using the findings. RESULTS: Antiretrovirals were detected in 27% of samples taken from 'previously undiagnosed' attendees, who did not have an HIV test but were HIV positive as detected by unlinked anonymous testing, indicating nondisclosure; 24% of such samples from MSM had antiretrovirals present compared with 32% of heterosexual men and women. Antiretrovirals were detected in 33% of samples from London clinics and in 21% from non-London clinics. Following adjustment, the estimated prevalence of undiagnosed HIV decreased nonsignificantly from 3.04% (95% confidence interval 2.71-3.41) to 2.66% (2.35-3.01) among men who have sex with men (MSM), 0.31% (0.26-0.37) to 0.30% (0.25-0.36) in heterosexual men and 0.40% (0.35-0.46) to 0.37% (0.32-0.43) in women; 7% of MSM who do not have an HIV test at a clinic visit will be infected with HIV and remain unaware of their infection. CONCLUSION: Nondisclosure of HIV status to healthcare professionals occurs among clinic attendees. Adjustment for nondisclosure results in a small, nonsignificant decrease in the prevalence of undiagnosed HIV estimated from the unlinked anonymous survey in sexual health clinics. Testing the population of MSM not having an HIV test remains a priority as levels of undiagnosed HIV are high. PMID- 26372478 TI - Cerebral vasoreactivity is impaired in treated, virally suppressed HIV-infected individuals. AB - OBJECTIVE: To compare cerebral vasoreactivity, a measure of cerebrovascular endothelial function, between treated, virally suppressed HIV-infected individuals and HIV-uninfected controls and to evaluate the effect of HIV specific factors on cerebral vasoreactivity. METHODS: Cross-sectional study of 65 antiretroviral therapy-treated, virally suppressed HIV-infected individuals and 28 HIV-uninfected controls. Participants underwent noninvasive assessment of cerebral vasoreactivity using transcranial Doppler ultrasound and inhaled carbon dioxide (CO2). We used mixed effects multivariable linear regression to determine the association of HIV infection and HIV-specific factors with cerebral vasoreactivity. RESULTS: Mean age was 57.2 years for HIV-infected participants and 53.5 years for HIV-uninfected controls. Most participants (95%) were men. Twenty-six per cent of HIV-infected participants were nonwhite compared to 32% of controls. Among HIV-infected participants, mean CD4 cell count was 596 cells/MUl, and mean duration of viral suppression was 7.8 years. Cerebral vasoreactivity in response to hypercapnia (cerebral VRhyper) was lower in HIV-infected individuals compared to uninfected controls (3.23 versus 3.81%, P = 0.010). After adjusting for demographic and vascular risk factors, HIV infection was independently associated with lower cerebral vasoreactivity (-0.86%, 95% CI -1.30 to -0.42%, P < 0.001). We did not find a statistically significant effect of recent or nadir CD4 cell count on cerebral vasoreactivity. There was a trend toward higher cerebral vasoreactivity for each additional year of viral suppression. CONCLUSION: Treated, virally suppressed HIV infection negatively impacted cerebral vasoreactivity even after adjustment for traditional vascular risk factors. These data highlight the potential contribution of cerebrovascular endothelial dysfunction to the elevated risk of stroke observed in HIV-infected individuals. PMID- 26372480 TI - Towards depersonalized abacavir therapy: chemical modification eliminates HLA B*57 : 01-restricted CD8+ T-cell activation. AB - OBJECTIVE: Exposure to abacavir is associated with T-cell-mediated hypersensitivity reactions in individuals carrying human leukocyte antigen (HLA) B57 : 01. To activate T cells, abacavir interacts directly with endogenous HLA B57 : 01 and HLA-B57 : 01 expressed on the surface of antigen presenting cells. We have investigated whether chemical modification of abacavir can produce a molecule with antiviral activity that does not bind to HLA-B57 : 01 and activate T cells. DESIGN: An interdisciplinary laboratory study using samples from human donors expressing HLA-B57 : 01. Researchers were blinded to the analogue structures and modelling data. METHODS: Sixteen 6-amino substituted abacavir analogues were synthesized. Computational docking studies were completed to predict capacity for analogue binding within HLA-B57 : 01. Abacavir-responsive CD8 clones were generated to study the association between HLA-B57 : 01 analogue binding and T-cell activation. Antiviral activity and the direct inhibitory effect of analogues on proliferation were assessed. RESULTS: Major histocompatibility complex class I-restricted CD8 clones proliferated and secreted IFNgamma following abacavir binding to surface and endogenous HLA-B57 : 01. Several analogues retained antiviral activity and showed no overt inhibitory effect on proliferation, but displayed highly divergent antigen-driven T-cell responses. For example, abacavir and N-propyl abacavir were equally potent at activating clones, whereas the closely related analogues N-isopropyl and N-methyl isopropyl abacavir were devoid of T-cell activity. Docking abacavir analogues to HLA-B57 : 01 revealed a quantitative relationship between drug-protein binding and the T-cell response. CONCLUSION: These studies demonstrate that the unwanted T-cell activity of abacavir can be eliminated whilst maintaining the favourable antiviral profile. The in-silico model provides a tool to aid the design of safer antiviral agents that may not require a personalized medicines approach to therapy. PMID- 26372481 TI - A randomized, double-blind, placebo-controlled, short-term monotherapy study of doravirine in treatment-naive HIV-infected individuals. AB - OBJECTIVE: To assess the antiviral activity, pharmacokinetics, and safety of doravirine in nonnucleoside reverse transcriptase inhibitor-naive, HIV-infected men. DESIGN: Double-blind, randomized, two-panel, dose-escalation study. METHODS: In two sequential panels, 18 individuals received doravirine [25 mg (Panel A) or 200 mg (Panel B)] or matching placebo once daily for 7 days. Plasma samples were collected daily for measurement of HIV-1 RNA levels and doravirine pharmacokinetics. RESULTS: For the mean change from baseline in HIV RNA (log10 copies/ml) at 24 h after the day 7 dose, the mean difference (90% confidence interval) between doravirine and placebo was -1.37 (-1.60, -1.14) in the 25-mg group and -1.26 (-1.51, -1.02) in the 200-mg group. None of the participants had viral breakthrough. Increases in mean AUC0-24 h, Cmax, and C24 h were slightly less than dose-proportional, with median Tmax of 1.0-2.0 h. Steady state was achieved after 3-5 days of once-daily dosing. At steady state, accumulation ratios (day 7/day 1) for AUC0-24 h, Cmax, and C24 h were 1.2-1.6. The calculated effective t1/2 (10-16 h) was similar to that in HIV-uninfected individuals. Adverse events were limited in number, transient, and generally mild to moderate in intensity. One participant had a serious adverse event of elevated liver enzymes (judged probably not drug related) in concurrence with a newly acquired hepatitis C infection. CONCLUSION: Doravirine monotherapy demonstrated robust antiviral activity at both dose levels, without evidence of viral resistance, and was generally well tolerated. Doravirine pharmacokinetics in HIV-infected individuals were similar to those in uninfected individuals receiving similar doses in prior studies. PMID- 26372482 TI - Rectal squamous cell carcinoma in immunosuppressed populations: is this a distinct entity from anal cancer? AB - OBJECTIVE: Squamous cell carcinoma (SCC) of the rectum is rare, but as with anal cancer, risk may be increased among immunosuppressed individuals. We assessed risk of rectal SCC in HIV-infected people. DESIGN: Population-based registry. METHODS: We utilized the HIV/AIDS Cancer Match, a linkage of US HIV and cancer registries (1991-2010), to ascertain cases of anal SCC, rectal SCC, rectal non SCC, and colon non-SCC. We compared risk in HIV-infected persons with the general population using standardized incidence ratios (SIRs) and evaluated risk factors using Poisson regression. We reviewed cancer registry case notes to confirm site and histology for a subset of cases. RESULTS: HIV-infected persons had an excess risk of rectal SCC compared with the general population (SIR = 28.9; 95% CI 23.2 35.6), similar to the increase for anal SCC (SIR = 37.3). Excess rectal SCC risk was most pronounced among HIV-infected MSM (SIR = 61.2). Risk was not elevated for rectal non-SCC (SIR = 0.88) or colon non-SCC (SIR = 0.63). Individuals diagnosed with AIDS had higher rectal SCC rates than those with HIV-only (incidence rate ratio = 1.92; 95% CI 1.08-3.42). Based on available information, one-third of rectal SCCs were determined to be misclassified anal cancer. CONCLUSION: HIV-infected individuals, especially with advanced immunosuppression, appear to have substantially elevated risk for rectal SCC. As for anal SCC, rectal SCC risk was highest in MSM, pointing to involvement of a sexually transmitted infection such as human papillomavirus. Site misclassification was present, and detailed information on tumour location is needed to prove that rectal SCC is a distinct entity. PMID- 26372483 TI - Effects of integrated interventions on transmission risk and care continuum outcomes in persons living with HIV: meta-analysis, 1996-2014. AB - BACKGROUND: Reducing HIV infection and improving outcomes along the continuum of HIV care are high priorities of the US National HIV/AIDS strategy. Interventions that target multiple problem behaviors simultaneously in an integrated approach (referred to as integrated interventions) may improve prevention and care outcomes of persons living with HIV (PLWH). This systematic review and meta analysis examines the effects of integrated interventions. METHODS: A systematic review, including both electronic and hand searches, was conducted to identify randomized controlled trials (RCTs) published between 1996 and 2014 that were designed to target at least two of the following behaviors among PLWH: HIV transmission risk behaviors, HIV care engagement, and medication adherence. Effect sizes were meta-analyzed using random-effects models. RESULTS: Fifteen RCTs met the inclusion criteria. Integrated interventions significantly reduced sex without condoms [odds ratio (OR) = 0.74, 95% confidence interval (CI) = 0.59, 0.94, P = 0.013, 13 effect sizes] and had marginally significant effects on improving medication adherence behaviors (OR = 1.35, 95% CI = 0.98, 1.85, P = 0.063, 12 effect sizes) and undetectable viral load (OR = 1.46, 95% CI = 0.93, 2.27, P = 0.098, seven effect sizes). Significant intervention effects on at least two outcomes were seen in RCTs tailored to individual needs, delivered one on one, or in settings wherein PLWH received services or care. CONCLUSION: Integrated interventions produced some favorable prevention and care continuum outcomes in PLWH. How to incorporate integrated interventions with other combination HIV prevention strategies to reach the optimal impact requires further research. PMID- 26372484 TI - The dolutegravir R263K resistance mutation in HIV-1 integrase is incompatible with the emergence of resistance against raltegravir. AB - OBJECTIVE: Although the integrase inhibitor dolutegravir (DTG) has demonstrated greater resilience than other antiretroviral drugs at withstanding the emergence of HIV-1 resistance mutations, such substitutions can develop, albeit rarely, in treatment-experienced integrase inhibitor-naive individuals. The most common substitution in integrase under those circumstances is R263K whereas another substitution that was selected against DTG in tissue culture was G118R. The objective of this study was to determine the effects of these DTG-specific resistance substitutions on the ability of HIV-1 to become resistant against either of two other integrase inhibitors, raltegravir (RAL) and elvitegravir (EVG). DESIGN AND METHODS: We performed tissue culture selection experiments using DTG-resistant viruses containing integrase substitutions at positions R263K, H51Y/R263K, E138K/R263K, G118R and H51Y/G118R in the presence of increasing concentrations of either RAL or EVG. Changes in integrase sequences were monitored by genotyping. RESULTS: The presence of the R263K substitution delayed the emergence of resistance against RAL whereas the simultaneous presence of either the H51Y or E138K secondary substitutions in combination with R263K somewhat mitigated this inhibitory effect. In contrast, resistance against EVG appeared earlier than in wild-type virus in viruses containing the R263K and E138K/R263K DTG-associated resistance substitutions. CONCLUSION: The DTG resistant R263K substitution antagonized the development of HIV-1 resistance against RAL while partially facilitating the occurrence of resistance against EVG. PMID- 26372485 TI - Randomized noninferiority trial of two maternal single-dose nevirapine-sparing regimens to prevent perinatal HIV in Thailand. AB - OBJECTIVES: Perinatal single-dose nevirapine (sdNVP) selects for resistance mutations. The objective of this trial was to compare two maternal sdNVP-sparing regimens with standard zidovudine (ZDV)/sdNVP prophylaxis. DESIGN: PHPT-5 was a randomized, partially double-blind placebo-controlled, noninferiority trial in Thailand (NCT00409591). Study participants were women with CD4 of at least 250 cells/MUl and their infants. METHODS: All women received ZDV from 28 weeks' gestation and their newborn infants for one week. Women were also randomized to receive NVP-NVP (reference): maternal intrapartum sdNVP with a 7-day 'tail' of ZDV along with lamivudine, and infant NVP (one dose immediately, another 48 h later); infant-only NVP: maternal placebos for sdNVP and the 'tail', with infant NVP; LPV/r: maternal LPV/r starting at 28 weeks. Infants were formula-fed. HIV diagnosis was determined by DNA-PCR. RESULTS: Four-hundred and thirty-five women were randomized between January 2009 and September 2010. Accrual was terminated prematurely following a change in Thai guidelines recommending antiretroviral combination therapy for all pregnant women. Data on 405 mothers and 407 live-born children were analyzed. Baseline characteristics were similar between arms. Intent-to-treat transmission rates were 3.8% (95% confidence interval: 1.2-8.6) in NVP-NVP, 1.6% (0.2-5.6) in infant-only NVP, and 1.4% (0.4-5.1) in LPV/r arms. As-treated rates were 2.2% (0.5-6.4), 3.2% (0.9-7.9), and 1.5% (0.2-5.2), respectively. Factors independently associated with transmission were prophylaxis duration less than 8 weeks (adjusted odds ratio 15.5; 3.6-66.1) and viral load at baseline at least 4 log10copies/ml (adjusted odds ratio 10.9; 1.3-91.5). Regimens appeared well tolerated. CONCLUSION: Transmission rates in all arms were low but noninferiority was not proven. Antiretroviral prophylaxis for at least 8 weeks before delivery is necessary to minimize transmission risk. PMID- 26372486 TI - Renal dysfunction among HIV-infected patients starting antiretroviral therapy in Mwanza, Tanzania. PMID- 26372487 TI - Six-month outcomes of HIV-infected patients given short-course fluconazole therapy for asymptomatic cryptococcal antigenemia. AB - OBJECTIVE: In HIV-infected adults in sub-Saharan Africa, asymptomatic cryptococcal antigenemia at the time of antiretroviral therapy (ART) initiation is associated with more than 20% increased mortality. Provisional recommendations for treatment of asymptomatic cryptococcal antigenemia are neither well substantiated nor feasible in many resource-poor settings. After hospitals in Tanzania implemented a programme providing serum cryptococcal antigen (CrAg) screening with 4-week intensive fluconazole treatment for CrAg-positive patients, we were asked to assess the impact of this programme on mortality. DESIGN: In this retrospective operational research study, we documented 6-month outcomes of HIV-infected adults who had had CD4 cell counts less than 200 cells/MUl at the time of starting ART and had been screened for cryptococcal antigenemia over a period of 15 months. METHODS: We randomly selected three CrAg-negative patients, matched for ART start date, for every CrAg-positive patient who had been identified and treated with the 4-week intensive fluconazole course. The primary outcome was 6-month mortality in CrAg-positive and CrAg-negative groups. RESULTS: Mortality of CrAg-positive HIV-infected adults who received short-course fluconazole was noninferior to CrAg-negative adults. At 6 months, 16 of 18 CrAg positive and 46 of 54 CrAg-negative patients were alive [88.9% versus 85.1%, 3.9% absolute difference (one-sided 90% confidence interval +10.8%)]. No deaths in the CrAg-positive group seemed to be due to cryptococcal meningitis. CONCLUSION: This study suggests that even short-course intensive fluconazole could reduce the mortality of patients with asymptomatic cryptococcal antigenemia. Further studies are needed to confirm if this dose is both optimal for patient survival and feasible for wide implementation in resource-poor settings where mortality of cryptococcal disease is highest. PMID- 26372488 TI - The HIV care cascade in Switzerland: reaching the UNAIDS/WHO targets for patients diagnosed with HIV. AB - OBJECTIVES: To describe the HIV care cascade for Switzerland in the year 2012. DESIGN/METHODS: Six levels were defined: (i) HIV-infected, (ii) HIV-diagnosed, (iii) linked to care, (iv) retained in care, (v) on antiretroviral treatment (ART), and (vi) with suppressed viral load. We used data from the Swiss HIV Cohort Study (SHCS) complemented by a nationwide survey among SHCS physicians to estimate the number of HIV-patients not registered in the cohort. We also used Swiss ART sales data to estimate the number of patients treated outside the SHCS network. Based on the number of patients retained in care, we inferred the estimates for levels (i) to (iii) from previously published data. RESULTS: We estimate that (i) 15 200 HIV-infected individuals lived in Switzerland in 2012 (margins of uncertainty, 13 400-19 300). Of those, (ii) 12 300 (81%) were diagnosed, (iii) 12 200 (80%) linked, and (iv) 11 900 (79%) retained in care. Broadly based on SHCS network data, (v) 10 800 (71%) patients were receiving ART, and (vi) 10 400 (68%) had suppressed (<200 copies/ml) viral loads. The vast majority (95%) of patients retained in care were followed within the SHCS network, with 76% registered in the cohort. CONCLUSION: Our estimate for HIV infected individuals in Switzerland is substantially lower than previously reported, halving previous national HIV prevalence estimates to 0.2%. In Switzerland in 2012, 91% of patients in care were receiving ART, and 96% of patients on ART had suppressed viral load, meeting recent UNAIDS/WHO targets. PMID- 26372489 TI - Barriers to the uptake of postexposure prophylaxis among Nairobi-based female sex workers. AB - INTRODUCTION: Female sex workers (FSWs) in sub-Saharan Africa are at a particularly high risk for HIV infection. Postexposure prophylaxis (PEP) is available as part of an HIV care and prevention program through dedicated FSW clinics in Nairobi, Kenya, but is underutilized. We evaluated PEP knowledge, access, and adherence among clinic attendees. METHODS: An anonymous questionnaire was administered to unselected HIV-uninfected FSWs. Participants were dichotomized into high and low HIV risk categories based on self-reported sexual practices. Prior PEP use, knowledge, and adherence were then evaluated. RESULTS: One hundred and thirty-four HIV-uninfected FSWs participated, with 64 (48%) categorized as being at high risk for HIV acquisition. High-risk FSWs were less likely to have heard of or accessed PEP than lower risk FSWs (37.5 vs. 58.6%, P = 0.014; and 21.9 vs. 40.6%, P = 0.019, respectively). Among higher risk FSWs, those who had accessed PEP were more likely to report treatment for a genital infection (71.4 vs. 42.0%, P = 0.049) or sex with an HIV-infected man (62.5 vs. 37.5%, P = 0.042) during the last 6 months. However, only 35.7% of high-risk women accessing PEP completed a full course of treatment, and noncompleters were more likely to report prior unprotected sex with an HIV-infected man (P = 0.023). CONCLUSION: Despite freely available PEP for Nairobi-based FSWs, women at highest risk were less likely to have heard of PEP, access PEP, or complete the full course of therapy once initiated. Program delivery needs to be improved to ensure that FSW most at risk are able to benefit from this resource. PMID- 26372490 TI - Successful prevention of HIV mother-to-child transmission with dolutegravir-based combination antiretroviral therapy in a vertically infected pregnant woman with multiclass highly drug-resistant HIV-1. PMID- 26372491 TI - Should prophylaxis for Pneumocystis jirovecii pneumonia be considered in patients with a CD4+ count higher than 200 cells/MUl? PMID- 26372492 TI - Strengthening healthcare providers' skills to improve HIV services for MSM in Kenya. PMID- 26372493 TI - The state of UK pediatric anesthesia: a survey of National Health Service activity. AB - This secondary analysis of the 2013 United Kingdom National Health Service (NHS) Anaesthesia Activity Survey of the Fifth National Audit Project (of the Royal College of Anaesthetists and Association of Anaesthetists of Great Britain and Ireland) shows pediatric anesthesia activity in detail. A local coordinator (LC) in every NHS hospital collected data on patients undergoing any procedure managed by an anesthetist. Questionnaires had 30 question categories. Each LC was randomized to a 2-day period. The pediatric age groups were infants, (<1 year), preschool age (1-5 year), and school age children (6-15 year). The median questionnaire return rate was 98%. The annual caseload was estimated to be 486 900 children: 36 500 infants, 184 700 preschool age, and 265 800 school age children. Almost 90% of children (1-15 year) were ASA 1 or 2 and the substantial majority underwent routine nonurgent ear nose and throat, dental, orthopaedics, or general surgery procedures; 65% were 'day cases'. One in six children were managed outside operating theater sites compared with one in 12 adults. Forty one per cent was in district general hospitals. Almost all ASA 4 and 5 children (89%) and infants (92%) were managed in specialist hospitals. 'Awake' cases and sedation accounted for only 2% of cases. There were notable differences in demography and anesthetic care compared with adults and between different age groups of children. These data enable analysis of the current state of UK pediatric anesthetic practice and highlight differences between pediatric and adult services. PMID- 26372494 TI - Comparison of interstitial brachytherapy and surgery as primary treatments for nasal vestibule carcinomas. AB - OBJECTIVES/HYPOTHESIS: Squamous cell carcinoma arising from the nasal vestibule is a rare condition accounting for about 1% of head and neck malignancies with several peculiarities concerning both staging and treatment. The aim of this study was to compare the oncological and functional results of two different treatment modalities for the primary site: surgery and brachytherapy. STUDY DESIGN: A case series with the comparison of two different treatment modalities. METHODS: We evaluate clinical and survival data of 12 untreated patients, enrolled by a multidisciplinary tumor board, comparing oncological, functional, and esthetic results after surgery or after interstitial brachytherapy as exclusive treatments for the primary site. The functional and esthetic outcome was subjectively rated by the patients using a five-point scale. RESULTS: Locoregional control and survival are not significantly different between patients primarily treated by surgery and by brachytherapy. The functional and esthetic outcome, as assessed by the degree of satisfaction of the patients, is significantly better after primary brachytherapy than after primary surgery (P = .014). CONCLUSIONS: In our experience brachytherapy, accomplished in close cooperation between surgeons and radiation oncologists, achieves oncological results that are not different from surgery, but with a higher degree of patient satisfaction, mainly due to the esthetic outcome. LEVEL OF EVIDENCE: 4. PMID- 26372495 TI - Open quantum system parameters for light harvesting complexes from molecular dynamics. AB - We extract the site energies and spectral densities of the Fenna-Matthews-Olson (FMO) pigment protein complex of green sulphur bacteria from simulations of molecular dynamics combined with energy gap calculations. Comparing four different combinations of methods, we investigate the origin of quantitative differences regarding site energies and spectral densities obtained previously in the literature. We find that different forcefields for molecular dynamics and varying local energy minima found by the structure relaxation yield significantly different results. Nevertheless, a picture averaged over these variations is in good agreement with experiments and some other theory results. Throughout, we discuss how vibrations-external or internal to the pigment molecules-enter the extracted quantities differently and can be distinguished. Our results offer some guidance to set up computationally more intensive calculations for a precise determination of spectral densities in the future. These are required to determine absorption spectra as well as transport properties of light harvesting complexes. PMID- 26372496 TI - Training students in research and scientific writing. PMID- 26372497 TI - [Thyroid pathology. Pre-test]. PMID- 26372498 TI - [An exceptional endocervical nodule]. PMID- 26372499 TI - [Pre-analytical quality in fluid samples cytopathology: Results of a survey from the French Society of Clinical Cytology]. AB - INTRODUCTION: The pre-analytical step includes sample collection, preparation, transportation and storage in the pathology unit where the diagnosis is performed. The pathologist ensures that pre-analytical conditions are in line with expectations. The lack of standardization for handling cytological samples makes this pre-analytical step difficult to harmonize. Moreover, this step depends on the nature of the sample: fresh liquid or fixed material, air-dried smears, liquid-based cytology. The aim of the study was to review the different practices in French structures of pathology on the pre-analytical phase concerning cytological fluids such as broncho-alveolar lavage (BALF), serous fluids and urine. METHODS: A survey was conducted on the basis of the pre analytical chapter of the ISO 15189 and sent to 191 French pathological structures (105 public and 86 private). RESULTS: Fifty-six laboratories replied to the survey. Ninety-five per cent have a computerized management system and 70% a manual on sample handling. The general instructions requested for the patients and sample identification were highly correctly filled with a short time routing and additional tests prescription. By contrast, information are variable concerning the clinical information requested and the type of tubes for collecting fluids and the volumes required as well as the actions taken in case of non-conformity. For the specific items concerning BALF, serous fluids and urine, this survey has shown a great heterogeneity according to sample collection, fixation and of clinical information. CONCLUSION: This survey demonstrates that the pre-analytical quality for BALF, serous fluids and urine is not optimal and that some corrections of the practices are recommended with a standardization of numerous steps in order to increase the reproducibility of additional tests such as immunocytochemistry, cytogenetic and molecular biology. Some recommendations have been written. PMID- 26372500 TI - [Thyroid pathology. Case n(o) 1: Papillary carcinoma: encapsulated follicular variant]. PMID- 26372501 TI - [Cardiac fibroma: A rare cause of sudden child death]. AB - We report the case of a 3-year-old child who died from the consequences of a cardio-respiratory arrest despite reanimation procedures. Echocardiography and magnetic resonance imaging (MRI) revealed a mass of the free wall of the left ventricle. Autopsy confirmed the existence of a solitary myocardial tumor, well circumscribed, firm, with a whitish and trabeculated cut surface. Histologically, the tumor consisted of bundles of spindle-shaped and regular cells mingling with collagen and elastic fibers, insinuating themselves between myocytes in periphery. Calcifications were present. After immunohistochemistry, the cells were highlighted by anti-actin smooth muscle antibody; but they were not highlighted by anti-desmin, anti-beta catenin and anti-Ki67 antibodies. The diagnosis of cardiac fibroma was made. The primary cardiac tumors of child are rare and usually benign. They are essentially represented by rhabdomyoma and fibroma. Cardiac fibroma mostly occurs during the first year of life. It can be revealed by cardiac insufficiency, arrhythmia, chest pain or sudden death. PMID- 26372502 TI - Testing independence of bivariate interval-censored data using modified Kendall's tau statistic. AB - In this paper, we study a nonparametric procedure to test independence of bivariate interval censored data; for both current status data (case 1 interval censored data) and case 2 interval-censored data. To do it, we propose a score based modification of the Kendall's tau statistic for bivariate interval-censored data. Our modification defines the Kendall's tau statistic with expected numbers of concordant and disconcordant pairs of data. The performance of the modified approach is illustrated by simulation studies and application to the AIDS study. We compare our method to alternative approaches such as the two-stage estimation method by Sun et al. (Scandinavian Journal of Statistics, 2006) and the multiple imputation method by Betensky and Finkelstein (Statistics in Medicine, 1999b). PMID- 26372503 TI - In response to a new theory on the pathogenesis of acquired cholesteatoma: Mucosal traction. PMID- 26372504 TI - Orchid conservation in the biodiversity hotspot of southwestern China. AB - Xishuangbanna is on the northern margins of tropical Asia in southwestern China and has the largest area of tropical forest remaining in the country. It is in the Indo-Burma hotspot and contains 16% of China's vascular flora in <0.2% of the country's total area (19,690 km(2) ). Rapid expansion of monoculture crops in the last 20 years, particularly rubber, threatens this region's exceptional biodiversity. To understand the effects of land-use change and collection on orchid species diversity and determine protection priorities, we conducted systematic field surveys, observed markets, interviewed orchid collectors, and then determined the conservation status of all orchids. We identified 426 orchid species in 115 genera in Xishuangbanna: 31% of all orchid species that occur in China. Species richness was highest at 1000-1200 m elevation. Three orchid species were assessed as possibly extinct in the wild, 15 as critically endangered, 82 as endangered, 124 as vulnerable, 186 as least concern, and 16 as data deficient. Declines over 20 years in harvested species suggested over collection was the major threat, and utility value (i.e., medicinal or ornamental value) was significantly related to endangerment. Expansion of rubber tree plantations was less of a threat to orchids than to other taxa because only 75 orchid species (17.6%) occurred below the 1000-m-elevation ceiling for rubber cultivation, and most of these (46) occurred in nature reserves. However, climate change is projected to lift this ceiling to around 1300 m by 2050, and the limited area at higher elevations reduces the potential for upslope range expansion. The Xishuangbanna Tropical Botanical Garden is committed to achieving zero plant extinctions in Xishuangbanna, and orchids are a high priority. Appropriate in and ex situ conservation strategies, including new protected areas and seed banking, have been developed for every threatened orchid species and are being implemented. PMID- 26372505 TI - A Phenotypic Screen for Functional Mutants of Human Adenosine Deaminase Acting on RNA 1. AB - Adenosine deaminases acting on RNA (ADARs) are RNA-editing enzymes responsible for the conversion of adenosine to inosine at specific locations in cellular RNAs. ADAR1 and ADAR2 are two members of the family that have been shown to be catalytically active. Earlier, we reported a phenotypic screen for the study of human ADAR2 using budding yeast S. cerevisiae as the host system. While this screen has been successfully applied to the study of ADAR2, it failed with ADAR1. Here, we report a new reporter that uses a novel editing substrate and is suitable for the study of ADAR1. We screened plasmid libraries with randomized codons for two important residues in human ADAR1 (G1007 and E1008). The screening results combined with in vitro deamination assays led to the identification of mutants that are more active than the wild type protein. Furthermore, a screen of the ADAR1 E1008X library with a reporter construct bearing an A*G mismatch at the editing site suggests one role for the residue at position 1008 is to sense the identity of the base pairing partner for the editing site adenosine. This work has provided a starting point for future in vitro evolution studies of ADAR1 and led to new insight into ADAR's editing site selectivity. PMID- 26372506 TI - Diagnostic Performance of Contrast-Enhanced MRI With Secretin-Stimulated MRCP for Non-Calcific Chronic Pancreatitis: A Comparison With Histopathology. AB - OBJECTIVES: Diagnosis of non-calcific chronic pancreatitis (NCCP) in patients presenting with chronic abdominal pain is challenging and controversial. Contrast enhanced magnetic resonance imaging (MRI) with secretin-stimulated MRCP (sMRCP) offers a safe and noninvasive modality to diagnose mild CP, but its findings have not been correlated with histopathology. We aimed to assess the correlation of a spectrum of MRI/sMRCP findings with surgical histopathology in a cohort of NCCP patients undergoing total pancreatectomy with islet autotransplantation (TPIAT). METHODS: Adult patients undergoing TPIAT for NCCP between 2008 and 2013 were identified from our institution's surgery database and were included if they had MRI/sMRCP within a year before surgery. Histology was obtained from resected pancreas at the time of TPIAT by wedge biopsy of head, body, and tail, and was graded by a gastrointestinal pathologist who was blinded to the imaging features. A fibrosis score (FS) of 2 or more was considered as abnormal, with FS >=6 as severe fibrosis. A multivariate regression analysis was performed for MRI features predicting fibrosis, after taking age, sex, smoking, alcohol, and body mass index (BMI) into consideration. A quantitative receiver operating characteristic (ROC) curve analysis was performed and Spearman rank correlation coefficient (r) was calculated. RESULTS: Fifty-seven patients (females=49, males=8) with NCCP and MRI/sMRCP were identified. ROC curve analysis showed that two or more MRI/sMRCP features provided the best balance of sensitivity (65%), specificity (89%), and accuracy (68%) to differentiate abnormal (FS>=2) from normal pancreatic tissue. Two or more features provided the best cutoff (sensitivity 88%, specificity 78%) for predicting severe fibrosis (FS>=6). There was a significant correlation between the number of features and severity of fibrosis (r=0.6, P<0.0001). A linear regression after taking age, smoking, and BMI into consideration showed that main pancreatic duct irregularity, T1-weighted signal intensity ratio between pancreas and paraspinal muscle, and duodenal filling after secretin injection to be significant independent predictors of fibrosis. CONCLUSIONS: A strong correlation exists between MRI/sMRCP findings and histopathology of NCCP. PMID- 26372507 TI - Covered metallic stents with an anti-migration design vs. uncovered stents for the palliation of malignant gastric outlet obstruction: a multicenter, randomized trial. AB - OBJECTIVES: Previous studies reported comparable stent patency between covered self-expandable metallic stents (SEMS) and uncovered SEMS (UCS) for palliation of malignant gastric outlet obstruction (GOO). The aim of this study was to evaluate the efficacy and safety of the newly developed WAVE-covered SEMS (WCS), which has an anti-migration design, compared with UCS in gastric cancer patients with symptomatic GOO. METHODS: A total of 102 inoperable gastric cancer patients with symptomatic GOO were prospectively enrolled from five referral centers and randomized to undergo UCS or WCS placement. Stent patency and recurrence of obstructive symptoms were assessed at 8 weeks and 16 weeks after stent placement. RESULTS: At the 8-week follow-up, both stent patency rates (72.5% vs. 62.7%) and re-intervention rates (19.6% vs. 19.6%) were comparable between the WCS and the UCS groups. Both stent stenosis (2.4% vs. 8.1%) and migration rates (9.5% vs. 5.4%) were comparable between WCS and UCS groups. At the 16-week follow-up, however, the WCS group had a significantly higher stent patency rate than the UCS group (68.6% vs. 41.2%). Re-intervention rates in the WCS and UCS groups were 23.5% and 39.2%, respectively. Compared with the UCS group, the WCS group had a significantly lower stent restenosis rate (7.1% vs. 37.8%) and a comparable migration rate (9.5% vs. 5.4%). Overall stent patency was significantly longer in the WCS group than in the UCS group. No stent-associated significant adverse events occurred in either the WCS or UCS groups. In the multivariate analysis, WCS placement and chemotherapy were identified as independent predictors of 16 week stent patency. CONCLUSIONS: WCS group showed comparable migration rate and significantly more durable long-term stent patency compared with UCS group for the palliation of GOO in patients with inoperable gastric cancer. PMID- 26372509 TI - One sensor acoustic emission localization in plates. AB - Acoustic emissions are elastic waves accompanying damage processes and are therefore used for monitoring the health state of structures. Most of the traditional acoustic emission techniques use a trilateration approach requiring at least three sensors on a 2D domain in order to localize sources of acoustic emission events. In this paper, we present a new approach which requires only a single sensor to identify and localize the source of acoustic emissions in a finite plate. The method proposed makes use of the time reversal principle and the dispersive nature of the flexural wave mode in a suitable frequency band. The signal shape of the transverse velocity response contains information about the propagated paths of the incoming elastic waves. This information is made accessible by a numerical time reversal simulation. The effect of dispersion is reversed and the original shape of the flexural wave is restored at the origin of the acoustic emission. The time reversal process is analyzed first for an infinite Mindlin plate, then by a 3D FEM simulation which in combination results in a novel acoustic emission localization process. The process is experimentally verified for different aluminum plates for artificially generated acoustic emissions (Hsu-Nielsen source). Good and reliable localization was achieved for a homogeneous quadratic aluminum plate with only one measurement. PMID- 26372508 TI - Are ESPGHAN "biopsy-sparing" guidelines for celiac disease also suitable for asymptomatic patients? AB - OBJECTIVES: In 2012, European Society of Pediatric Gastroenterology, Hepatology, and Nutrition published novel guidelines on celiac disease (CD) diagnosis. Symptomatic children with serum anti-transglutaminase (anti-tTG) antibody levels >=10 times upper limit of normal (ULN) could avoid duodenal biopsies after positive HLA test and serum anti-endomysial antibodies (EMAs). So far, both asymptomatic and symptomatic patients with anti-tTG titer <10 times ULN should undergo upper endoscopy with duodenal biopsies to confirm diagnosis. The aim of this study was to assess the accuracy of serological tests to diagnose CD in asymptomatic patients. METHODS: We retrospectively reviewed data of 286 patients (age range: 10 months to 17 years) with CD diagnosis based on elevated titer of anti-tTG, EMA positivity, and histology. All patients were distinguished between symptomatic and asymptomatic; histological lesions were graded according to the Marsh-Oberhuber (MO) criteria. Fisher exact test was applied to analyze both groups in terms of diagnostic reliability of serological markers. RESULTS: A total of 196 patients (68.53%) had anti-tTG titers >=10 times ULN. Among them, a group of 156 patients (79.59%) also had symptoms suggestive of CD ("high-titer" symptomatic); of these, 142 patients (91.02%) showed severe lesion degree (3a, 3b, 3c MO). Conversely, 40 out of 196 patients (20.40%) were asymptomatic ("high titer" asymptomatic) and 37 patients (92.5%) of them showed severe lesion degree (3a, 3b, 3c MO). No difference in histological damage was found between "high titer" symptomatic and "high-titer" asymptomatic children (Fisher exact test, P=1.000). CONCLUSIONS: If confirmed in large multicenter prospective studies, the "biopsy-sparing" protocol seems to be applicable to both symptomatic and asymptomatic patients with anti-tTG titer >=10 times ULN, positive EMA, and HLA DQ2/DQ8. PMID- 26372510 TI - Premature aging in chronic kidney disease and chronic obstructive pulmonary disease: similarities and differences. AB - PURPOSE OF REVIEW: There is increasing clinical and pathophysiological evidence that a premature aging process is involved in the pathogenesis of systemic complications of many chronic organ diseases, which result in analogous phenotypes, including premature vascular aging, osteoporosis and muscle wasting. Novel developments from research into the aging process will, therefore, have relevance for understanding complications of organ diseases, such as chronic kidney disease and chronic obstructive pulmonary disease. The aim of the present article is to combine recent literature on aging mechanisms with evidence on the pathogenesis of systemic complications of these two chronic debilitating disorders. RECENT FINDINGS: Recently, nine hallmarks of aging have been identified. In this review, we argue that all of these hallmarks are relevant for the pathogenesis of premature aging processes in chronic obstructive pulmonary disease and chronic kidney disease. Additionally, organ-specific alterations in proaging mechanisms, which reveal differences in phenotype against a generic background of premature aging, will be addressed. However, within patient populations who share a common diagnosis, clusters of patients with different phenotypes may be identified, which may show overlap with patients with other chronic diseases. SUMMARY: An increased understanding of the premature aging process as well as its systemic consequences may pave the way for 'precision' intervention as well as shared treatment opportunities between chronic debilitating diseases of various causes. PMID- 26372511 TI - The impact of gut microbiota on brain and behaviour: implications for psychiatry. AB - PURPOSE OF REVIEW: The gut microbiota has become a focus of research for those interested in the brain and behaviour. Here, we profile the gut microbiota in a variety of neuropsychiatric syndromes. RECENT FINDINGS: Multiple routes of communication between the gut and brain have been established and these include the vagus nerve, immune system, short chain fatty acids and tryptophan. Developmentally, those born by caesarean section have a distinctly different microbiota in early life to those born per vaginum. At the other extreme, individuals who age with considerable ill-heath tend to show narrowing in microbial diversity. Recently, the gut microbiota has been profiled in a variety of conditions including autism, major depression and Parkinson's disease. There is still debate as to whether or not these changes are core to the pathophysiology or merely epiphenomenal. SUMMARY: The current narrative suggests that certain neuropsychiatric disorders might be treated by targeting the microbiota either by microbiota transplantation, antibiotics or psychobiotics. PMID- 26372512 TI - Micronutrient and amino acid losses in acute renal replacement therapy. AB - PURPOSE OF REVIEW: A wide range of renal replacement therapies is now available to support patients with acute kidney injury. These treatments utilize diffusion, convection or a combination of these mechanisms to remove metabolic waste products from the bloodstream. It is inevitable that physiologically important substances including micronutrients will also be removed. Here we review current knowledge of the extent of micronutrient loss, how it varies between treatment modalities and its clinical significance. RECENT FINDINGS: Very few studies have specifically investigated micronutrient loss in renal replacement therapy for acute kidney injury. Recent data suggest that trace elements and amino acids are lost during intermittent dialysis, hybrid therapies such as sustained low efficiency diafiltration and continuous therapies. Extent of micronutrient loss appears to vary with treatment type, with continuous convection-based treatments probably causing greatest losses. SUMMARY: Patients with acute kidney injury are at high risk of disease-related malnutrition. The use of renal replacement therapy, although often essential for life support, results in loss of micronutrients into the filtrate or dialysate. Losses are probably greater with continuous convective treatments, but it is not yet known whether these losses are clinically significant or whether their replacement would improve patient outcomes. PMID- 26372513 TI - Regional white matter development in very preterm infants: perinatal predictors and early developmental outcomes. AB - BACKGROUND: Preterm infants are at risk for white matter (WM) injury and adverse neurodevelopmental outcomes. METHODS: Serial diffusion tensor magnetic resonance imaging data were obtained from very preterm infants (N = 78) born <30 wk gestation imaged up to four times from 26-42 wk postmenstrual age. Slopes were calculated for fractional anisotropy (FA) and mean diffusivity (MD) within regions of interest for infants with >=2 scans (N = 50). Sixty-five children underwent neurodevelopmental testing at 2 y of age. RESULTS: FA slope for the posterior limb of the internal capsule was greater than other regions. The anterior limb of the internal capsule (ALIC), corpus callosum, and optic radiations demonstrated greater FA slope with increasing gestational age. Infants with patent ductus arteriosus had lower FA slope in the ALIC. MD slope was lower with prolonged ventilation or lack of antenatal steroids. At 2 y of age, lower motor scores were associated with lower FA in the left but higher FA in the right inferior temporal lobe at term-equivalent age. Better social-emotional competence was related to lower FA in the left cingulum bundle. CONCLUSION: This study demonstrates regional variability in the susceptibility/sensitivity of WM maturation to perinatal factors and relationships between altered diffusion measures and developmental outcomes in preterm neonates. PMID- 26372514 TI - High protein intake in neonatal period induces glomerular hypertrophy and sclerosis in adulthood in rats born with IUGR. AB - BACKGROUND: Intrauterine growth restriction (IUGR) and postnatal nutrition are risk factors for cardiovascular and renal diseases in both humans and animals. The long-term renal effects of protein intake early in life remain unknown. The objective was to evaluate the effects of a neonatal feeding with high protein (HP) milk on renal functions and structure in IUGR male rats. METHODS: Maternal gestational low protein diet was used to produce IUGR. At day 5, IUGR pups were gastrostomized in the "pup-in-the cup" model and received either normal protein (NP) milk or HP (+50% protein content) milk until day 21. After weaning, the animals were fed the same standard diet. Renal functions and structure were assessed at postnatal day 18 (D18) and in adult offspring. RESULTS: During the preweaning period, the postnatal weight gain between the two groups was unaffected. On D18, kidneys from HP offspring were heavier with significant glomerular hypertrophy (+40%, P < 0.05). HP diet was associated with significant proteinuria and glomerulosclerosis (+49%, P < 0.05). Glomerular number was unaltered. CONCLUSION: Neonatal HP feeding following IUGR affects renal functions and structure at adulthood. These alterations may result from a single nephron glomerular hyperfiltration. PMID- 26372515 TI - Respiratory adaptation and surfactant composition of unanesthetized male and female lambs differ for up to 8 h after preterm birth. AB - BACKGROUND: Male preterm infants are more likely to experience respiratory distress syndrome than females. Our objectives were to determine if sex-related differences in physiological adaptation after preterm birth increase with time after birth and if the use of continuous positive airway pressure (CPAP) reduces these differences. METHODS: Unanesthetized lambs (9F, 8M) were delivered at 0.90 of term. Blood gases, metabolites, and cardiovascular and respiratory parameters were monitored in spontaneously breathing lambs for 8 h. Supplemental oxygen was administered via a face mask at 4 cmH2O CPAP. At 8 h, lung compliance was determined, and bronchoalveolar lavage fluid (BALF) was analyzed for total protein and surfactant phospholipids. Surfactant protein (SP) gene expression and protein expression of SP-A and pro-SP-C were determined in lung tissue. RESULTS: For 8 h after delivery, males had significantly lower arterial pH and higher Paco2, and a greater percentage of males were dependent on supplemental oxygen than females. Inspiratory effort was greater and lung compliance was lower in male lambs. Total protein concentration in BALF, SP gene expression, and SP-A protein levels were not different between sexes; pro-SP-C was 24% lower in males. CONCLUSION: The use of CPAP did not eliminate the male disadvantage, which continues for up to 8 h after preterm birth. PMID- 26372516 TI - Age-specific onset and distribution of the natural anticoagulant deficiency in pediatric thromboembolism. AB - BACKGROUND: The early diagnosis of inherited thrombophilia in children is challenging because of the rarity and hemostatic maturation. METHODS: We explored protein C (PC), protein S (PS), and antithrombin (AT) deficiencies in 306 thromboembolic patients aged <=20 y using the screening of plasma activity and genetic analysis. RESULTS: Reduced activities were determined in 122 patients (40%). Low PC patients were most frequently found in the lowest age group (0-2 y, 45%), while low PS or low AT patients were found in the highest age group (16-20 y; PS: 30% and AT: 20%). Genetic study was completed in 62 patients having no other causes of thromboembolism. Mutations were determined in 18 patients (8 PC, 8 PS, and 2 AT genes). Six of eight patients with PC gene mutation were found in age 0-2 y (75%), while six of eight patients with PS gene mutation were in 7-20 y. Two AT gene-mutated patients were older than 4 y. Four PC-deficient and two PS deficient patients carried compound heterozygous mutations. All but one PC gene mutated patient suffered from intracranial thromboembolism, while PS/AT gene mutated patients mostly developed extracranial venous thromboembolism. CONCLUSION: Stroke in low PC infants and deep vein thrombosis in low PS/AT school age children could be targeted for genetic screening of pediatric thrombophilias. PMID- 26372517 TI - Bifidobacterium animalis subsp. lactis BB-12 in reducing the risk of infections in early childhood. AB - BACKGROUND: Specific probiotic bacteria have proven to be effective in the prevention and treatment of infectious diseases in early life in at-risk populations. The impact of administration of Bifidobacterium animalis subsp. lactis BB-12 (BB-12) on the risk of acute infectious diseases was studied in healthy children. METHODS: In this double-blind, placebo-controlled study, 109 1 mo-old infants were assigned randomly to a probiotic group receiving a BB-12 containing tablet (n = 55) or a placebo (n = 54). Test tablets were administered to the infants twice a day (daily dose of BB-12 10 billion colony-forming units) until the age of 2 y with a novel slow-release pacifier or a spoon. Breastfeeding habits, pacifier use, dietary habits, medications, and all signs and symptoms of acute infections were registered in diaries by parents and in questionnaires by trained professionals. RESULTS: The infants receiving BB-12 were reported to have experienced fewer respiratory tract infections (RTIs; 87 vs. 100%; risk ratio: 0.87; 95% confidence interval: 0.76, 1.00; P = 0.033) than the controls. No significant differences between the groups were observed in reported gastrointestinal symptoms, otitis media, or fever. The baseline characteristics of the two groups were similar, as was the duration of breastfeeding. CONCLUSION: Administration of BB-12 in early childhood may reduce RTIs. PMID- 26372519 TI - Serum concentrations of vascular endothelial growth factor in relation to retinopathy of prematurity. AB - BACKGROUND: The role of vascular endothelial growth factor (VEGF) in the pathogenesis of retinopathy of prematurity (ROP) has been clearly established. However, little is known about temporal changes in circulating VEGF concentrations in the preterm infant. The objective was to determine the longitudinal serum concentrations of VEGF in relation to ROP. METHODS: This study included 52 infants born at <31 wk gestational age (non-ROP n = 33, nonproliferative ROP n = 10, treated for ROP n = 9). VEGF concentrations were analyzed in blood samples collected at birth, at 3 d postnatal age, and then weekly until at least a gestational age of 35 wk. RESULTS: VEGF concentrations at birth did not differ between groups, independent of later ROP status. In contrast, VEGF serum concentrations were significantly higher at first detection of ROP in infants who were later treated for ROP compared to infants without ROP. At the time of laser therapy, serum VEGF concentrations did not differ between groups. CONCLUSION: Circulatory concentrations of VEGF, in infants who later developed severe ROP, were elevated at the time when ROP first was detected but not at the time when current treatment most often occurred. This supports the need for further studies of circulating VEGF in relation to the timing of ROP treatment. PMID- 26372520 TI - First molecular evidence of Coxiella burnetii infecting ticks in Cuba. AB - Coxiella burnetii is the causative agent of Q fever. In order to explore the occurrence of C. burnetii in ticks, samples were collected from horses, dogs and humans living in a Cuban occidental community. The species most commonly recovered were Amblyomma mixtum (67%), Rhipicephalus sanguineus s.l. (27%) and Dermacentor nitens (6%). Specific IS1111 PCR and amplicon sequencing allowed the identification of C. burnetii DNA in A. mixtum collected from a domestic horse. These findings, for first time in Cuba, indicate the need for an in-depth assessment of the C. burnetii occurrence in hosts and humans at risk of infection. PMID- 26372518 TI - Influence of breastfeeding and postnatal nutrition on cardiovascular remodeling induced by fetal growth restriction. AB - BACKGROUND: Our aim was to determine the influence of breastfeeding and postnatal nutrition on cardiovascular remodeling induced by fetal growth restriction (FGR). METHODS: A cohort study including 81 children with birthweight <10th centile (FGR) and 121 with adequate fetal growth for gestational age (AGA) was conducted. Cardiovascular endpoints were left ventricular sphericity index (LVSI), carotid intima-media thickness (cIMT), and blood pressure (BP) at 4-5 y of age. The combined effect of FGR and postnatal variables-including breastfeeding, fat dietary intake, and BMI-on cardiovascular endpoints was assessed by linear and robust regressions. RESULTS: FGR was the strongest predictor of cardiovascular remodeling in childhood, leading to lower LVSI and increased cIMT and BP as compared with AGA. Breastfeeding >6 mo (coefficient: 0.0982) and healthy-fat dietary intake (coefficient: -0.0128) showed an independent beneficial effect on LVSI and cIMT, respectively. Overweight/obesity induced an additional increment of 1 SD on cIMT in FGR children (interaction coefficient: 0.0307) when compared with its effect in AGA. BMI increased systolic BP (coefficient: 0.7830) while weight catch-up increased diastolic BP (coefficient: 4.8929). CONCLUSIONS: Postnatal nutrition ameliorates cardiovascular remodeling induced by FGR. Breastfeeding and healthy-fat dietary intake improved while increased BMI worsened cardiovascular endpoints, which opens opportunities for targeted postnatal interventions from early life. PMID- 26372521 TI - Outcomes in endocrine cancer surgery are affected by racial, economic, and healthcare system demographics. AB - OBJECTIVES/HYPOTHESIS: Surgeon experience has been recognized in several clinical fields as a significant element of superior management outcomes. In this study, we seek to assess the association between surgeon volume and patients' community health status with the outcomes of thyroid and parathyroid surgery indicated for primary malignancies. STUDY DESIGN: A cross-sectional study utilizing the State Inpatient Databases, 2010-2011, for Florida, New York, and Washington was merged with the County Health Rankings database. METHODS: International Classification of Diseases, Ninth Revision codes were used to identify adult (>=18 years) patients who underwent thyroidectomy or parathyroidectomy indicated for primary malignancies. RESULTS: A total of 6,347 records were included. Compared to high volume surgeons, patients treated by low-volume surgeons were more likely to develop postoperative complications in the 1-month period after the operation (odds ratio: 4.34, 95% confidence interval: 3.31-5.70, P < .001). Furthermore, both low- and intermediate-volume surgeons were associated with a longer hospital stay (>2 days) and a higher risk of admission to the intensive care unit (P < .01 each). Cost of health services was significantly in the highest quartile (>$10,254.66) for patients treated by low-volume surgeons (P < .001). Patients who lived in communities of poor health measures had a higher risk of postoperative complications (16.3% vs. 11.8%, P = .030) independent of the clinical presentation and management type. Patients living in high health-risk communities and those of black and Hispanic backgrounds were more likely to be treated by low-volume surgeons (P < .001 each). CONCLUSIONS: The surgeon's volume and the patient's living conditions are crucial and independent factors in multiple aspects of endocrine cancer management. LEVEL OF EVIDENCE: 4 Laryngoscope, 126:775-781, 2016. PMID- 26372522 TI - Low Level of Evidence and Methodologic Quality of Clinical Outcome Studies on Cartilage Repair of the Ankle. AB - PURPOSE: To examine the level of evidence and methodologic quality of studies reporting surgical treatments for osteochondral lesions of the ankle. METHODS: A search was performed using the PubMed/Medline, Embase, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and Cochrane databases for all studies in which the primary objective was to report the outcome after surgical treatment of osteochondral lesions of the ankle. Studies reporting outcomes of microfracture, bone marrow stimulation, autologous osteochondral transplantation, osteochondral allograft transplantation, and autologous chondrocyte implantation were the focus of this analysis because they are most commonly reported in the literature. Two independent investigators scored each study from 0 to 100 based on 10 criteria from the modified Coleman Methodology Score (CMS) and assigned a level of evidence using the criteria established by the Journal of Bone and Joint Surgery. Data were collected on the study type, year of publication, number of surgical procedures, mean follow-up, preoperative and postoperative American Orthopaedic Foot & Ankle Society score, measures used to assess outcome, geography, institution type, and conflict of interest. RESULTS: Eighty-three studies reporting the results of 2,382 patients who underwent 2,425 surgical procedures for osteochondral lesions of the ankle met the inclusion criteria. Ninety percent of studies were of Level IV evidence. The mean CMS for all scored studies was 53.6 of 100, and 5 areas were identified as methodologically weak: study size, type of study, description of postoperative rehabilitation, procedure for assessing outcome, and description of the selection process. There was no significant difference between the CMS and the type of surgical technique (P = .1411). A statistically significant patient-weighted correlation was found between the CMS and the level of evidence (r = -0.28, P = .0072). There was no statistically significant patient-weighted correlation found between the CMS and the institution type (r = 0.05, P = .6480) or financial conflict of interest (r = -0.16, P = .1256). CONCLUSIONS: Most studies assessing the clinical outcomes of cartilage repair of the ankle are of a low level of evidence and of poor methodologic quality. LEVEL OF EVIDENCE: Level IV, systematic review of Level I through IV studies. PMID- 26372523 TI - Influence of Different Tibial Fixation Techniques on Initial Stability in Single Stage Anterior Cruciate Ligament Revision With Confluent Tibial Tunnels: A Biomechanical Laboratory Study. AB - PURPOSE: To kinematically and biomechanically compare 4 different types of tibial tunnel management in single-stage anterior cruciate ligament (ACL) revision reconstruction with the control: primary ACL reconstruction using a robotic-based knee testing setup. METHODS: Porcine knees and flexor tendons were used. One hundred specimens were randomly assigned to 5 testing groups: (1) open tibial tunnel, (2) bone plug technique, (3) biodegradable interference screw, (4) dilatation technique, and (5) primary ACL reconstruction. A robotic/universal force-moment sensor testing system was used to simulate the KT-1000 (MEDmetric, San Diego, CA) and pivot-shift tests. Cyclic loading and load-to-failure testing were performed. RESULTS: Anterior tibial translation increased significantly with all of the techniques compared with the intact ACL (P < .05). In the simulated KT 1000 test, groups 2 and 3 achieved results equal to those of primary ACL reconstruction (P > .05). The open tunnel and dilated tunnel techniques showed significantly greater anterior tibial translation (P < .05). The results of the simulated pivot-shift test were in accordance with those of the KT-1000 test. No significant differences could be observed regarding stiffness or maximum load to failure. However, elongation was significantly lower in the primary ACL reconstruction group compared with groups 1 and 3 (P = .02 and P = .03, respectively). CONCLUSIONS: Filling an incomplete and incorrect tibial tunnel with a press-fit bone plug or a biodegradable interference screw in a standardized laboratory situation provided initial biomechanical properties and knee stability comparable with those of primary ACL reconstruction. In contrast, the dilatation technique or leaving the malplaced tunnel open did not restore knee kinematics adequately in this model. Backup extracortical fixation should be considered because the load to failure depends on the extracortical fixation when an undersized interference screw is used for aperture fixation. CLINICAL RELEVANCE: Our biomechanical results could help orthopaedic surgeons to optimize the results of primary ACL revision with incomplete, incorrect tunnel placement. PMID- 26372525 TI - 2015 Award Recipients-Bette Kay Kleinschmidt-DeMasters, MD and John Q. Trojanowski, MD, PhD. PMID- 26372526 TI - Solvent switchable dual emission from a bichromophoric ruthenium-BODIPY complex. AB - A ruthenium(II) polypyridyl-BODIPY dyad is presented which exhibits a solvent switchable dual emission. Intense oxygen sensitive emission from the ruthenium centre and O2 independent emission from the BODIPY centre, are both observed in organic media. In aqueous media, the BODIPY emission is reversibly switched off leaving only a ruthenium centred emission. The materials are interesting both as self-referenced O2 probes and for cell/tissue imaging. PMID- 26372527 TI - Insights into the catalytic mechanism of synthetic glutathione peroxidase mimetics. AB - Glutathione Peroxidase (GPx) is a key selenoenzyme that protects biomolecules from oxidative damage. Extensive research has been carried out to design and synthesize small organoselenium compounds as functional mimics of GPx. While the catalytic mechanism of the native enzyme itself is poorly understood, the synthetic mimics follow different catalytic pathways depending upon the structures and reactivities of various intermediates formed in the catalytic cycle. The steric as well as electronic environments around the selenium atom not only modulate the reactivity of these synthetic mimics towards peroxides and thiols, but also the catalytic mechanisms. The catalytic cycle of small GPx mimics is also dependent on the nature of peroxides and thiols used in the study. In this review, we discuss how the catalytic mechanism varies with the substituents attached to the selenium atom. PMID- 26372529 TI - Molecular epidemiological view on Shiga toxin-producing Escherichia coli causing human disease in Germany: Diversity, prevalence, and outbreaks. AB - Infections by intestinal pathogenic Escherichia coli (E. coli) are among those causing a high mortality and morbidity due to diarrheal disease and post infection sequelae worldwide. Since introduction of the Infection Protection Act in Germany 2001, these pathogens rank third among bacterial infections of the gastrointestinal tract. As a major pathovar Shiga toxin-producing E. coli (STEC) which include enterohemorrhagic E. coli (EHEC) play a leading role in occurrence of sporadic cases and disease outbreaks. An outstanding example is the large outbreak in spring 2011 caused by EHEC/EAEC O104:H4. To monitor and trace back STEC infections, national surveillance programs have been implemented including activities of the German National Reference Centre for Salmonella and other Enteric Bacterial Pathogens (NRC). This review highlights advances in our understanding of STEC in the last 20 years of STEC surveillance by the NRC. Here important characteristics of STEC strains from human infections and outbreaks in Germany between 1997 and 2013 are summarized. PMID- 26372528 TI - Decoding human swallowing via electroencephalography: a state-of-the-art review. AB - Swallowing and swallowing disorders have garnered continuing interest over the past several decades. Electroencephalography (EEG) is an inexpensive and non invasive procedure with very high temporal resolution which enables analysis of short and fast swallowing events, as well as an analysis of the organizational and behavioral aspects of cortical motor preparation, swallowing execution and swallowing regulation. EEG is a powerful technique which can be used alone or in combination with other techniques for monitoring swallowing, detection of swallowing motor imagery for diagnostic or biofeedback purposes, or to modulate and measure the effects of swallowing rehabilitation. This paper provides a review of the existing literature which has deployed EEG in the investigation of oropharyngeal swallowing, smell, taste and texture related to swallowing, cortical pre-motor activation in swallowing, and swallowing motor imagery detection. Furthermore, this paper provides a brief review of the different modalities of brain imaging techniques used to study swallowing brain activities, as well as the EEG components of interest for studies on swallowing and on swallowing motor imagery. Lastly, this paper provides directions for future swallowing investigations using EEG. PMID- 26372532 TI - Intimal Problems: A Pictorial Review of Nontraumatic Aortic Disease at Multidetector Computed Tomography. AB - Nontraumatic aortic diseases include a spectrum of disorders, many of which result in high morbidity and mortality. This article highlights the multidetector computed tomography appearance of common and uncommon nontraumatic aortic entities: dissection, intramural hematoma, penetrating atherosclerotic ulcer, pseudoaneurysm, aneurysm, acute thrombus, chronic occlusion, and vasculitis. Additionally, classical imaging mimics and pitfalls are addressed. Radiologists should feel confident identifying these conditions and providing accurate diagnoses to expedite patient care and prevent devastating, even fatal outcomes. PMID- 26372530 TI - Lactobacillus crispatus mediates anti-inflammatory cytokine interleukin-10 induction in response to Chlamydia trachomatis infection in vitro. AB - Chlamydia trachomatis, a human pathogen, is a Gram-negative bacillus and a compulsory intracellular parasite. It is the most common cause of bacterial sexually transmitted infections in both industrialized and developing countries. In women, untreated genital infections can result in devastating consequences such as pelvic inflammatory disease, ectopic pregnancy, and even infertility. Lactobacillus crispatus is an important urogenital species that is routinely found in the vagina of healthy women. Lactobacilli are involved in the maintenance of the normal vaginal microbiota and their dominance in the vagina suggests that they play a crucial role in protecting the genitourinary tract against pathological conditions. Lactobacilli can act through the activation of the immune system, but C. trachomatis is able to effectively evade immune surveillance in some individuals. The aim of our study was to investigate the immunomodulatory efficacy of the potential probiotic strain L. crispatus in HeLa and J774 cells subjected to C. trachomatis infection by studying the expression of the inflammatory cytokines IL-6, IL-8, TNF-alpha and IL-10. Our results demonstrated, firstly, the lack of any cytotoxic effect on the epithelial cells and macrophages when treated with L. crispatus and its supernatant; in addition, L. crispatus and its supernatant inhibited C. trachomatis adhesion and infectivity in human epithelial cells and macrophages. Our study then showed that L. crispatus and its supernatant reduced IL-6, IL-8 and TNF-alpha production in C. trachomatis-infected HeLa and J774 cells. In contrast, a significant upregulation of the IL-10 expression in HeLa and J774 cells by L. crispatus and supernatant was also demonstrated. Our data indicate that L. crispatus specifically enhances the production of the IL-10 anti-inflammatory cytokine in contrast to the inhibitory effect of L. crispatus on the pro-inflammatory cytokines. PMID- 26372533 TI - Three-Dimensional NiCo2O4@Polypyrrole Coaxial Nanowire Arrays on Carbon Textiles for High-Performance Flexible Asymmetric Solid-State Supercapacitor. AB - In this article, we report a novel electrode of NiCo2O4 nanowire arrays (NWAs) on carbon textiles with a polypyrrole (PPy) nanosphere shell layer to enhance the pseudocapacitive performance. The merits of highly conductive PPy and short ion transport channels in ordered NiCo2O4 mesoporous nanowire arrays together with the synergistic effect between NiCo2O4 and PPy result in a high specific capacitance of 2244 F g(-1), excellent rate capability, and cycling stability in NiCo2O4/PPy electrode. Moreover, a lightweight and flexible asymmetric supercapacitor (ASC) device is successfully assembled using the hybrid NiCo2O4@PPy NWAs and activated carbon (AC) as electrodes, achieving high energy density (58.8 W h kg(-1) at 365 W kg(-1)), outstanding power density (10.2 kW kg( 1) at 28.4 W h kg(-1)) and excellent cycling stability (~89.2% retention after 5000 cycles), as well as high flexibility. The three-dimensional coaxial architecture design opens up new opportunities to fabricate a high-performance flexible supercapacitor for future portable and wearable electronic devices. PMID- 26372534 TI - [Approach and complications associated with suburethral synthetic slings in women: Systematic review and meta-analysis]. AB - INTRODUCTION: We aim to assess the complications associated with different approaches used in female suburethral sling surgery. METHOD: We performed a research on Medline using the following keywords: "suburethral slings", "complications", "safety" and "randomized". Only randomized clinical trials including women and reporting intra- and postoperative complications associated with the retropubic (RP) approach; TOT and/or TVT-O were included. The meta analysis was conducted using the Review Manager (RevMan 5.3) software delivered by the "Cochrane Library". RESULTS: Out of 176 articles, 23 were included in synthesis. Risks of bladder perforation during surgery (60/1482 vs 5/1479; OR=6.44; 95% CI [3.32-12.50]) and postoperative urinary retention (48/1160 vs 24/1159; OR=1.93; 95% CI [1.26-3.12]) were significantly higher with the RP approach, when compared with the transobturator (TO) approach (TOT or TVT-O). Conversely, the risk of prolonged postoperative pain was significantly lower after RP approach, when compared with TO approach (24/1156 vs 69/1149; OR=0.36; 95% CI [0.23-0.56]). Risks of intraoperative urethral injury, postoperative erosion and de novo overactive bladder were comparable between the two approaches. Data regarding the comparison between TOT and TVT-O were scarce and did not allow us to conclude about complications associated with. CONCLUSION: The RP approach was associated with a significant risk of bladder perforation and postoperative urinary retention. The TO approach was associated with a higher risk of prolonged postoperative pain. PMID- 26372536 TI - Pediatric Origins of Nephrolithiasis-Associated Atherosclerosis. AB - OBJECTIVES: To determine if nephrolithiasis-associated atherosclerosis has pediatric origins and to consider possible association between kidney stones and atherosclerosis-related proteins. STUDY DESIGN: We matched children aged 12-17 years with kidney stones and without kidney stones. Carotid artery intima-media thickness (cIMT) was measured by ultrasound. Participants' urine was investigated by enzyme-linked immunosorbent assay for the atherosclerosis-related proteins fibronectin 1, macrophage scavenger receptor 1, osteopontin, and vascular cell adhesion molecule 1 levels, and normalized to urine creatinine levels. RESULTS: Subjects with nephrolithiasis had higher cIMT in the right common carotid artery and overall mean measurement. Urine osteopontin and fibronectin 1 were significant predictors of cIMT. CONCLUSIONS: We have provided initial preliminary evidence that nephrolithiasis-associated atherosclerosis has pediatric origins and performed studies that begin to identify potential reasons for the association of nephrolithiasis and vascular disease. PMID- 26372535 TI - Early Life Antibiotic Exposure Is Not Associated with Growth in Young Children of Vellore, India. AB - OBJECTIVES: To estimate the effects of antibiotic exposures in the first 6 months of life on short- and long-term growth. STUDY DESIGN: In a prospective observational cohort study of 497 children from Vellore, India, we estimated short-term effects of antibiotics during the first 6 months using longitudinal general linear regression to model weight-for-age, height-for-age, and weight-for height z-scores in monthly intervals. To estimate long-term effects, we modeled growth from 6 months to 3 years as a function of antibiotic use in the first 6 months. We also estimated the effects of antibiotics on the monthly relative risks of underweight, stunting, and wasting in the first 6 months and to 3 years. RESULTS: Underweight, stunting, and wasting were common in this population: 31%, 32%, and 15% on average after 6 months of age, respectively. There was no association between antibiotic exposures before 6 months and growth during that period. From 6 months to 3 years, adjusted absolute differences in weight and height were small (approximately -100 g and no more than -2 mm overall, respectively) and not statistically significant. CONCLUSIONS: Antibiotic exposures early in life were not associated with increased or decreased growth. The combination of malnutrition and recurrent illness likely complicate the relationship between antibiotic exposures and growth among children in low and middle-income countries. PMID- 26372537 TI - Complexity and forensic pathology. AB - It has become increasingly apparent that nonlinearity and complexity are the norm in human physiological systems, the relevance of which is informing an enhanced understanding of basic pathological processes such as inflammation, the host response to severe trauma, and critical illness. This article will explore how an understanding of nonlinear systems and complexity might inform the study of the pathophysiology of deaths of medicolegal interest, and how 'complexity thinking' might usefully be incorporated into modern forensic medicine and forensic pathology research, education and practice. PMID- 26372538 TI - Tissue-dependent VEGF and GLUT1 induction in a rat hemorrhage model: With regard to diagnostic application of mRNA quantification in forensic pathology. AB - Systemic hypoxia is inevitably involved in the death process to a varying extent. Hypoxia-response factors proved useful in forensic pathology in previous studies; however, fundamental investigations using animal models are expected to reinforce the findings from autopsy practice. An animal experiment using a rat model of fixed-volume hemorrhage was performed to apply basic insight into quantitative mRNA analyses in forensic pathology. Male Sprague-Dawley rats (n=5) were anesthetized, bled from the femoral artery (24ml/kg; about 30% of total circulating blood volume), and decapitated after 1 or 2h. Tissue samples of the heart, brain (hippocampus), kidney, liver, lung and skeletal muscle were collected for RNA and protein analyses. Quantitative analyses of VEGF, GLUT1 and GAPDH mRNAs were performed with TaqMan real-time RT-PCR assay. In the sham control without bleeding, mRNA quantification revealed the tissue-dependent mRNA levels in physiological condition. Relative quantification of VEGF and GLUT1 showed significant inductions under hemorrhage at the mRNA level, using GAPDH as endogenous reference. In conclusion, tissue-dependent induction patterns of VEGF and GLUT1 were revealed in the volume-fixed hemorrhage rat model. This study could practically guide the selection of mRNA markers and tissue samples in forensic pathology related to tissue ischemia and cellular hypoxia for autopsy cases. PMID- 26372539 TI - Utility of ICD-9-CM Codes for Identification of Allergic Drug Reactions. AB - BACKGROUND: The epidemiology of allergic drug reactions is poorly understood due, in large part, to difficulty in identifying true cases in population data sets. Use of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes is a potentially valuable approach that requires formal evaluation. OBJECTIVE: To better understand the utility of ICD-9-CM codes for identification of allergic drug reactions, including the validation of specific codes by chart review. METHODS: We reviewed randomly sampled medical records of patients treated in the emergency department (ED) between January 1, 2001, and December 31, 2006, with ICD-9-CM codes for drug allergy and E codes (E930-949) for adverse drug reactions. RESULTS: During the 6-year period, 11,130 charts were identified by ICD-9-CM and E codes and 1,634 were reviewed. Allergic drug reactions were found in 444 (27%) of the reviewed ED visits. The codes that identified the highest percentage of true allergic drug reactions were dermatitis due to drug (693.0; 87%), adverse reaction to drug (995.2; 52%), and anaphylaxis (995.0; 38%). Patients with both an ICD-9-CM code and an E code had a high likelihood of having an allergic drug reaction (76%). Most allergic drug reactions were attributed to antibiotics (42%), intravenous contrast (7%), and nonsteroidal anti-inflammatory drugs (6%). The estimated frequency of allergic drug reactions increased from 0.49% of ED visits in 2001 to 0.94% in 2012. CONCLUSIONS: Specific ICD-9-CM and E codes can be used in combination to identify allergic drug reactions. Further study of these codes in the inpatient and outpatient settings is necessary to better understand the utility of diagnosis codes for improving epidemiologic research on drug allergy. PMID- 26372540 TI - Progression of Common Variable Immunodeficiency Interstitial Lung Disease Accompanies Distinct Pulmonary and Laboratory Findings. AB - BACKGROUND: Common variable immunodeficiency may be complicated by interstitial lung disease, which leads to worsened morbidity and mortality in some. Although immunomodulatory treatment has efficacy, choice of patient, duration of treatment, and long-term follow-up are not available. Interstitial lung disease appears stable in certain instances, so it is not known whether all patients will develop progressive disease or require immunomodulatory therapy. OBJECTIVE: This study aims to determine if all common variable immunodeficiency patients with interstitial lung disease have physiological worsening, and if clinical and/or laboratory parameters may correlate with disease progression. METHODS: A retrospective review of medical records at Mount Sinai Medical Center in New York was conducted for referred patients with common variable immunodeficiency, CT scan-confirmed interstitial lung disease, and periodic pulmonary function testing covering 20 or more months before immunomodulatory therapy. Fifteen patients were identified from the retrospective review and included in this study. RESULTS: Of the 15 patients with common variable immunodeficiency, 9 had physiological worsening of interstitial lung disease adapted from consensus guidelines, associated with significant reductions in forced expiratory volume in 1 second, forced vital capacity, and diffusion capacity of the lung for carbon monoxide. Those with progressive lung disease also had significantly lower mean immunoglobulin G levels, greater increases and highest levels of serum immunoglobulin M (IgM), and more significant thrombocytopenia. CONCLUSION: Interstitial lung disease resulted in physiological worsening in many, but not all subjects, and was associated with suboptimal immunoglobulin G replacement. Those with worsening pulmonary function tests, elevated IgM, and severe thrombocytopenic episodes appear to be at highest risk for progressive disease. Such patients may benefit from immunomodulatory treatment. PMID- 26372541 TI - Trace amine-associated receptor 1 activation silences GSK3beta signaling of TAAR1 and D2R heteromers. AB - Trace amine-associated receptor 1 (TAAR1) activation by selective endogenous agonists modulates dopaminergic neurotransmission. This results in antipsychotic like behavior in vivo which might be initiated by an interaction of TAAR1 and dopamine D2L receptor (D2R). Here we analyzed the functional link between TAAR1 and D2R using highly potent and selective TAAR1 agonists, and newly generated tools such as TAAR1 knock-out and TAAR1 overexpressing rats as well as specific anti-rat TAAR1 antibodies. We provide data from co-immunoprecipitation experiments supporting a functional interaction of the two receptors in heterologous cells and in brain tissue. Interaction of TAAR1 with D2R altered the subcellular localization of TAAR1 and increased D2R agonist binding affinity. Using specific beta-arrestin 2 (betaArr2) complementation assays we show that the interaction of TAAR1 with D2R reduced betaArr2 recruitment to D2R. In addition, we report that besides Galphas-protein signaling TAAR1 also signals via betaArr2. In the presence of D2R, cAMP signaling of TAAR1 was reduced while its betaArr2 signaling was enhanced, resulting in reduced GSK3beta activation. These results demonstrate that betaArr2 signaling may be an important pathway for TAAR1 function and that the activation of the TAAR1-D2R complex negatively modulates GSK3beta signaling. Given that patients with schizophrenia or bipolar disorder show increased GSK3beta signaling, such a reduction of GSK3beta signaling triggered by the interaction of D2R with activated TAAR1 further supports TAAR1 as a target for the treatment of psychiatric disorders. PMID- 26372542 TI - Comorbidities, smoking status, and life expectancy among individuals eligible for lung cancer screening. AB - BACKGROUND: Lung cancer screening recommendations are based on results from the National Lung Screening Trial (NLST). The authors determined how the screening eligible US population differs from NLST participants in terms of characteristics that affect their ability to benefit from screening. METHODS: The authors identified respondents to the 2012 Health and Retirement Study (HRS), a national survey of individuals aged >=50 years who are eligible for screening based on US Preventive Services Task Force and Centers for Medicare and Medicaid Services criteria. Comorbidities, life expectancy, smoking history, and other characteristics were compared between the screening-eligible population and NLST participants. RESULTS: The authors estimated that in 2013, 8.4 million individuals (95% confidence interval, 7.9-8.9 million individuals) would have met the eligibility criteria for lung cancer screening established by the US Preventive Services Task Force. Compared with NLST participants, HRS screening eligible respondents were older, more likely to be current smokers, and more likely to have been diagnosed with comorbidities. The 5-year survival rate was 87% in the HRS screening-eligible individuals versus 93% in the NLST participants (P<.001, based on a 2-sided test). Life expectancy was 18.7 years in the HRS screening-eligible individuals versus 21.2 years in the NLST participants. CONCLUSIONS: The US population eligible for lung cancer screening is probably less likely to benefit from early detection than NLST participants because they face a high risk of death from competing causes. The results of the current study highlight the need for smoking cessation interventions targeting those patients eligible for screening and tools to help clinicians determine the potential benefits of screening in individual patients. PMID- 26372543 TI - Ustekinumab: The "New Kid on the Block" in the Treatment of Psoriatic Arthritis. AB - Psoriatic arthritis (PsA) is a chronic inflammatory seronegative spondyloarthritis associated with psoriasis. While TNF-alpha inhibitors have revolutionized the treatment of rheumatic diseases, including PsA, not all patients respond to these agents while others are unsuitable or intolerant to them. Thus, there is a need for additional treatment modalities with a novel mechanism of action. In the past years, the IL-23/Th17 axis has emerged as an important mechanism in the pathogenesis of PsA. Ustekinumab, a fully human IgG1kappa monoclonal antibody that targets the common subunit p40 of IL-12 and IL 23, has been shown in clinical trials, to be well-tolerated and effective in patients with active PsA. It improved signs and symptoms of PsA, inhibited radiographic progression and was effective in dactylitis, enthesitis, and skin disease, with a safety profile consistent with the one observed in patients with psoriasis. Moreover, it was to be effective in anti-TNF-alpha experienced patients, definitely fulfilling an unmet need in the management of PsA. PMID- 26372544 TI - [The situation regarding hypocomplementemic urticarial vasculitis in 2015]. PMID- 26372545 TI - [Pyoderma gangrenosum revealing colonic diverticulitis: Two cases]. AB - BACKGROUND: The association of pyoderma gangrenosum (PG) with colonic diverticulitis infection (DI) is relatively unknown. Herein, we describe two cases of PG with full recovery after colonic surgery. PATIENTS AND METHODS: Case 1: an 83-year-old man presented with lesions on his legs that had been present for several weeks, and a diagnosis of PG was confirmed histologically. Abdominopelvic computed tomography (CT) performed on account of biological inflammatory syndrome revealed DI complicated by abscesses. Following the failure of two different antibiotic regimens, sigmoidectomy was performed. Postoperatively, the skin lesions healed without local or systemic corticosteroids. Case 2: a 63-year-old woman presented PG resistant to local and systemic corticosteroids and dapsone for several months. A particularly severe flare was accompanied by abdominal pain and inflammatory syndrome. CT revealed perforated sigmoid DI. Sigmoidectomy was performed after failure of drug therapy. The patient's PG subsequently improved and had disappeared without recurrence at 24months. DISCUSSION: Both of these cases of PG revealed DI. The hypothesis is that DI constituted a source of colonic inflammation, sending out bacterial antigenic stimuli that resulted in PG through deposition of circulating immune complexes. Removal of this inflammatory source appears to have enabled healing of PG. CONCLUSION: DI must be added to the list of systemic diseases associated with PG. In the case of isolated PG, CT may be used to detect asymptomatic DI. Early diagnosis could prevent serious gastrointestinal complications. PMID- 26372547 TI - [Clinical evaluation of the severity of hidradenitis suppurativa]. AB - Treatment and long-term management of patients with chronic diseases require the use of instruments to measure severity and outcome. In the case of hidradenitis suppurativa, such instruments are currently poorly understood and utilised. Herein, we describe the main instruments, their scope of application, their qualities and their shortcomings. The Hurley classification, which was devised for surgical assessment and is limited to description of impairment at a given site, is too often used to assess overall severity in individual patients. The Sartorius score (and variants thereof) combines global and local measurements; it is widely used, but because of its hybrid nature, the global score, or PGA-HS, is currently used; the latter, focusing on inflammatory signs, is perfectly suitable for daily assessment of pharmaceutical treatment. The HiSCR score, derived from the foregoing grading system, is used as a global criterion in clinical trials. Patient-based instruments, such as pain or suppuration score, and, to a lesser extent, quality-of-life score constitute very useful supplements. Since the disease is extremely heterogeneous, no instruments cover the entire array of situations and the requirements of medical and surgical practitioners involved in the management of this patient population. PMID- 26372546 TI - [Macular lymphocytic arteritis and periarteritis nodosa: A case report showing diagnostic and nosological challenges posed by these two entities]. AB - BACKGROUND: Macular lymphocytic arteritis is a recently described type of cutaneous vasculitis involving vessels of medium size. Authors consider it as a form of polyarteritis nodosa. Herein we report a case of macular lymphocytic arteritis during the course of which periarteritis nodosa appeared. PATIENTS AND METHODS: A 50-year-old man, with no history other than chronic venous insufficiency of the lower limbs, presented with an asymptomatic eruption involving all four limbs, mainly the lower limbs, and appearing in episodes. Physical examination revealed brown macules, in some cases outlining the configuration of livedo reticularis. Laboratory findings were normal except for the presence of low levels of anticardiolipin activity at diagnosis, which had subsided three months later. Histological examination of the skin biopsy showed lymphocytic arteritis with some histiocytes and neutrophils, as well as an eosinophilic ring of parietal necrosis. Six months later, the patient developed multineuritis, leading to the diagnosis of polyarteritis nodosa. A diagnosis of cutaneous polyarteritis nodosa could also have been made based on the association of cutaneous livedo and locoregional polyneuritis without systemic involvement. DISCUSSION: The diagnosis of macular lymphocytic arteritis is based upon clinical and histological findings and upon disease progression. This entity seems to belong to the same spectrum as periarteritis nodosa, especially in the cutaneous form. Given the lack of knowledge concerning progression from macular lymphocytic arteritis to nodosa periarteritis, close patient monitoring is called for, as illustrated by our case report. PMID- 26372548 TI - [Acute blue urticaria following subcutaneous injection of patent blue dye]. AB - BACKGROUND: Patent blue (PB) is a lymphatic vessel dye commonly used in France for sentinel lymph node detection in breast cancer, and less frequently in melanoma, and which may induce hypersensitivity reactions. We report a case of acute blue urticaria occurring within minutes of PB injection. PATIENTS AND METHODS: Ten minutes after PB injection for sentinel lymph node detection during breast cancer surgery, a 49-year-old woman developed generalised acute blue urticaria and eyelid angioedema without bronchospasm or haemodynamic disturbance, but requiring discontinuation of surgery. Skin testing using PB and the anaesthetics given were run 6 weeks after the episode and confirmed PB allergy. PB was formally contra-indicated. DISCUSSION: Immediate hypersensitivity reactions to PB have been reported for between 0.24 and 2.2% of procedures. Such reactions are on occasion severe, chiefly involving anaphylactic shock. Two mechanisms are probably associated: non-specific histamine release and/or an IgE mediated mechanism. Skin tests are helpful in confirming the diagnosis of PB allergy. CONCLUSION: Blue acute urticaria is one of the clinical manifestations of immediate hypersensitivity reactions to patent blue dye. Skin tests must be performed 6 weeks after the reaction in order to confirm the diagnosis and formally contra-indicate this substance. PMID- 26372550 TI - Frequency and Type of Prosthetic Complications Associated with Interim, Immediately Loaded Full-Arch Prostheses: A 2-Year Retrospective Chart Review. AB - PURPOSE: The purpose of this report was to retrospectively evaluate implant and immediate full-arch prosthesis survival rates over a 24-month period; patients were consecutively treated with immediate occlusal loading. Dental arch, gender, and implant orientation (vertical vs. tilted) were also noted. MATERIALS AND METHODS: All Branemark System implants (Nobel Active) and interim, all-acrylic resin prostheses placed in patients following an All-on-FourTM protocol, in a single private practice were assessed by retrospective patient chart review. The amount of space provided surgically for implant restorative components and prostheses was determined from measurements of the vertical heights of the interim prostheses in the right/left anterior and posterior segments. These measurements were made in the laboratory. Interim prosthetic repairs (type, frequency, length of time from insertion) were analyzed by type, arch, gender, and implant orientation. Implant survival and insertion torque values were also measured. Inclusion criteria consisted of all Branemark System implants placed with the All-on-Four protocol from September 1, 2011, until August 31, 2013. Specific dietary instructions were given for the first 7 days immediately postoperatively and for the weeks prior to insertion of the definitive prostheses. RESULTS: One hundred twenty-nine patients, comprising 191 arches (766 implants) from September 1, 2011, until August 31, 2013, were included in the study. One patient experienced implant failure yielding an overall implant survival rate (SR) of 99.5% (762 of 766). Four hundred twenty-six of 430 maxillary implants and 336 of 336 mandibular implants survived for SRs of 99.1% and 100%, respectively. Regarding implant orientation, 415 of 417 tilted implants (SR 99.5%) and 343 of 345 (CSR 95.6%) vertical implants were noted to be clinically stable. Interim, all-acrylic resin prostheses were in place for a mean of 199.2 days; mandibular prostheses were in place for an average of 195.4 days; maxillary prostheses were in place for an average of 202.0 days. Thirty four of the 191 interim prostheses (17.8%) warranted at least one repair during the treatment period. The average overall implant insertion torque value was 60.74 Ncm; mandibular torque values averaged 63.08 Ncm; maxillary torque values averaged 59.00 Ncm. CONCLUSIONS: The results from this study suggest that dental arch, gender, and implant orientation for implants placed and immediately restored with interim, all-acrylic resin, full-arch prostheses per the All-on Four protocol did not have significant statistical or clinical effects on prosthetic complications of the interim prostheses or implant survival. Only one of the 129 patients experienced implant failures, indicating that the All-on-Four treatment protocol used in this study is a viable alternative to other protocols for rehabilitating edentulous patients. PMID- 26372549 TI - Effect of Carotene and Lycopene on the Risk of Prostate Cancer: A Systematic Review and Dose-Response Meta-Analysis of Observational Studies. AB - BACKGROUND: Many epidemiologic studies have investigated the association between carotenoids intake and risk of Prostate cancer (PCa). However, results have been inconclusive. METHODS: We conducted a systematic review and dose-response meta analysis of dietary intake or blood concentrations of carotenoids in relation to PCa risk. We summarized the data from 34 eligible studies (10 cohort, 11 nested case-control and 13 case-control studies) and estimated summary Risk Ratios (RRs) and 95% confidence intervals (CIs) using random-effects models. RESULTS: Neither dietary beta-carotene intake nor its blood levels was associated with reduced PCa risk. Dietary alpha-carotene intake and lycopene consumption (both dietary intake and its blood levels) were all associated with reduced risk of PCa (RR for dietary alpha-carotene intake: 0.87, 95%CI: 0.76-0.99; RR for dietary lycopene intake: 0.86, 95%CI: 0.75-0.98; RR for blood lycopene levels: 0.81, 95%CI: 0.69 0.96). However, neither blood alpha-carotene levels nor blood lycopene levels could reduce the risk of advanced PCa. Dose-response analysis indicated that risk of PCa was reduced by 2% per 0.2mg/day (95%CI: 0.96-0.99) increment of dietary alpha-carotene intake or 3% per 1mg/day (95%CI: 0.94-0.99) increment of dietary lycopene intake. CONCLUSIONS: alpha-carotene and lycopene, but not beta-carotene, were inversely associated with the risk of PCa. However, both alpha-carotene and lycopene could not lower the risk of advanced PCa. PMID- 26372551 TI - Effect of Retrograde Reaming for Tibiotalocalcaneal Arthrodesis on Subtalar Joint Destruction: A Cadaveric Study. AB - Recent published data have suggested successful union of subtalar and tibiotalar joints without formal debridement during tibiotalocalcaneal (TTC) fusion procedures. Although previous studies have reported on the importance of the proper guidewire starting point and trajectory to obtain appropriate hindfoot alignment for successful fusion, to our knowledge, no studies have quantified the amount of articular damage to the subtalar joint with retrograde reaming. We hypothesized that reaming would destroy >50% of the posterior facet of the subtalar joint. The bilateral lower extremities of 5 cadavers were obtained and the subtalar joints exposed. Retrograde TTC nail guidewires were inserted, and a 12-mm reamer was passed through the subtalar and ankle joints. Pre- and postreaming images of the subtalar joint were obtained to compare the amount of joint destruction after reaming. We found an average of 5.89% articular destruction of the talar posterior facet and an average of 4.01% articular destruction of the posterior facet of the calcaneus. No damage to the middle facets of the subtalar joint was observed. TTC nailing is a successful procedure for ankle and subtalar joint fusion. Published studies have reported successful subtalar union using TTC nailing without formal open debridement of the subtalar joint, preserving the soft tissue envelope. TTC nail insertion using a 12-mm reamer will destroy 5.89% and 4.01% of the respective talar and calcaneal posterior facets of the subtalar joint. PMID- 26372552 TI - Minimally Invasive Sinus Tarsi Approach With Cannulated Screw Fixation Combined With Vacuum-Assisted Closure for Treatment of Severe Open Calcaneal Fractures With Medial Wounds. AB - The aim of our prospective study was to investigate the clinical results and advantages of a minimally invasive sinus tarsi approach with cannulated screw fixation combined with vacuum-assisted closure for the treatment of severe open calcaneal fractures with medial wounds. A total of 31 patients (32 feet) with open calcaneal fractures who were admitted to our hospital from January 2008 to May 2013 were selected for the study and randomly divided into 2 groups: the cannulated screw group (n = 16 patients, 16 feet) and the plate group (n = 15 patients, 16 feet). The Bohler and Gissane angles were compared before and after surgery. The clinical results were evaluated using according to the American Orthopaedic Foot and Ankle Society ankle-hindfoot scale and the rate of infection. The follow-up duration for all patients ranged from 10 to 36 (mean 24) months. No statistically significant differences were found in the radiologic indicators, incidence of early postoperative complications, or American Orthopaedic Foot and Ankle Society ankle-hindfoot scores (p > .05) between the 2 groups. However, a statistically significant difference was seen in the duration of hospitalization (p < .05) between the 2 groups. A minimally invasive sinus tarsi approach with cannulated screw fixation combined with vacuum-assisted closure is an effective method for the treatment of severe open calcaneal fractures with medial wounds. It provides good reduction and requires fewer days of hospitalization. PMID- 26372554 TI - Belongingness in Early Secondary School: Key Factors that Primary and Secondary Schools Need to Consider. AB - It is unknown if, and how, students redefine their sense of school belongingness after negotiating the transition to secondary school. The current study used longitudinal data from 266 students with, and without, disabilities who negotiated the transition from 52 primary schools to 152 secondary schools. The study presents the 13 most significant personal student and contextual factors associated with belongingness in the first year of secondary school. Student perception of school belongingness was found to be stable across the transition. No variability in school belongingness due to gender, disability or household socio-economic status (SES) was noted. Primary school belongingness accounted for 22% of the variability in secondary school belongingness. Several personal student factors (competence, coping skills) and school factors (low-level classroom task-goal orientation), which influenced belongingness in primary school, continued to influence belongingness in secondary school. In secondary school, effort-goal orientation of the student and perception of their school's tolerance to disability were each associated with perception of school belongingness. Family factors did not influence belongingness in secondary school. Findings of the current study highlight the need for primary schools to foster belongingness among their students at an early age, and transfer students' belongingness profiles as part of the hand-over documentation. Most of the factors that influenced school belongingness before and after the transition to secondary are amenable to change. PMID- 26372555 TI - The Effects of Research & Development Funding on Scientific Productivity: Academic Chemistry, 1990-2009. AB - This article examines the relationship between Research & Development (R&D) funding and the production of knowledge by academic chemists. Using articles published, either raw counts or adjusted for quality, we find a strong, positive causal effect of funding on knowledge production. This effect is similar across subsets of universities, suggesting a relatively efficient allocation of R&D funds. Finally, we document a rapid acceleration in the rate at which chemical knowledge was produced in the late 1990s and early 2000s relative to the financial and human resources devoted to its production. PMID- 26372556 TI - A novel Pd-Cu-Zr hydrogen separation membrane with a high tolerance to sulphur poisoning. AB - The effects of the addition of small amount of Zr (less than 2 at%) to the fcc phase of the Pd-Cu hydrogen separation alloy were investigated. Hydrogen flux variations in Pd-Cu and Pd-Cu-Zr alloys in the presence of 1000 ppm H2S + H2 feed gas showed a marked effect of Zr addition in improving the resistance to sulphur poisoning. PMID- 26372557 TI - Global Identification of MicroRNAs and Their Targets in Barley under Salinity Stress. AB - Salinity is a major limiting factor for agricultural production worldwide. A better understanding of the mechanisms of salinity stress response will aid efforts to improve plant salt tolerance. In this study, a combination of small RNA and mRNA degradome sequencing was used to identify salinity responsive-miRNAs and their targets in barley. A total of 152 miRNAs belonging to 126 families were identified, of which 44 were found to be salinity responsive with 30 up-regulated and 25 down-regulated respectively. The majority of the salinity-responsive miRNAs were up-regulated at the 8h time point, while down-regulated at the 3h and 27h time points. The targets of these miRNAs were further detected by degradome sequencing coupled with bioinformatics prediction. Finally, qRT-PCR was used to validate the identified miRNA and their targets. Our study systematically investigated the expression profile of miRNA and their targets in barley during salinity stress phase, which can contribute to understanding how miRNAs respond to salinity stress in barley and other cereal crops. PMID- 26372559 TI - Correction: Selection of Orthologous Genes for Construction of a Highly Resolved Phylogenetic Tree and Clarification of the Phylogeny of Trichosporonales Species. PMID- 26372558 TI - Cytogenetic and Molecular Data Demonstrate that the Bryconinae (Ostariophysi, Bryconidae) Species from Southeastern Brazil Form a Phylogenetic and Phylogeographic Unit. AB - Brycon spp. occur in Neotropical watersheds to the west and east of the Andes, and as they are sensitive to anthropogenic changes, many these species are endangered in southeastern Brazil. Coastal rivers in southeastern Brazil are characterized by the presence of relatively few freshwater fish species and high endemism of this fauna. The objective of this study was to examine whether Brycon spp. occurring in the coastal basins of southeastern Brazil are monophyletic, using cytogenetic data, mitochondrial, and nuclear molecular markers. All the species showed a diploid number of 50 chromosomes, a conserved number within the subfamily Bryconinae. However, the karyotypic formulas were unique to most species, including Brycon devillei (26m+22sm+2st), Brycon ferox (26m+12sm+12st), Brycon insignis (22m+20sm+8st), Brycon opalinus, and Brycon vermelha (24m+20sm+6st), indicating the prevalence of pericentric and paracentric inversions in the chromosomal evolution of these species. All of them had nucleolar organizer regions in the first pair of subtelocentric chromosomes and no equilocal distribution of heterochromatin in the first pair of chromosomes of the karyotype. These two features, not seen in any other Brycon spp. examined to date, indicate that Bryconinae species from the Brazilian southeastern coastal basins, including the monotypic genus Henochilus, are monophyletic. Also, this is the first study that reports NOR location and C-banding patterns as synapomorphies for a Neotropical fish species group. The monophyly was also supported by a phylogenetic analysis of 16S rDNA (16S), cytochrome oxidase subunit I (COI), alpha-myosin (MYH6) genes and S72 intron molecular data. Our results partially corroborate the "Brycon acuminatus" group proposed by Howes in 1982: our proposed clade keeps B. devillei, B. ferox, and B. insignis; but it also includes B. opalinus, B. vermelha, and H. weatlandii whereas it excludes B. nattereri. The phylogeographic unit formed by Bryconinae species in southeastern Brazil reflects the long and isolated paleohydrological history of these coastal basins relative to the continental watersheds. PMID- 26372562 TI - Falling Stars as Seen From the Balloon: Albert Tissandier. PMID- 26372563 TI - Adi Nadimpalli, MD, on Doing Field Work With Doctors Without Borders. PMID- 26372564 TI - Finding What Works to Reduce Violence Against Women. PMID- 26372572 TI - Vaccination and the Lasker Awards: Enduring Legacies. PMID- 26372573 TI - The Lasker Awards--Recognizing and Valuing Investments in Cardiovascular Research. PMID- 26372574 TI - The Lasker Awards--Recognizing and Highlighting Oncology Research. PMID- 26372575 TI - On the Recognition of Global Excellence in Medical Research. PMID- 26372576 TI - The Human Microbiome and the Future Practice of Medicine. PMID- 26372577 TI - Epigenetics at the Crossroads of Genes and the Environment. PMID- 26372578 TI - A PIECE OF MY MIND. The Joy of Discovery. PMID- 26372579 TI - Modern Biological Research, Medical Practice, and Human Knowledge. PMID- 26372580 TI - Is It Possible to Recognize a Major Scientific Discovery? PMID- 26372581 TI - Prevention of Myopia in Children. PMID- 26372582 TI - Addressing Disparities in Academic Medicine: Moving Forward. PMID- 26372583 TI - Effect of Time Spent Outdoors at School on the Development of Myopia Among Children in China: A Randomized Clinical Trial. AB - IMPORTANCE: Myopia has reached epidemic levels in parts of East and Southeast Asia. However, there is no effective intervention to prevent the development of myopia. OBJECTIVE: To assess the efficacy of increasing time spent outdoors at school in preventing incident myopia. DESIGN, SETTING, AND PARTICIPANTS: Cluster randomized trial of children in grade 1 from 12 primary schools in Guangzhou, China, conducted between October 2010 and October 2013. INTERVENTIONS: For 6 intervention schools (n = 952 students), 1 additional 40-minute class of outdoor activities was added to each school day, and parents were encouraged to engage their children in outdoor activities after school hours, especially during weekends and holidays. Children and parents in the 6 control schools (n = 951 students) continued their usual pattern of activity. MAIN OUTCOMES AND MEASURES: The primary outcome measure was the 3-year cumulative incidence rate of myopia (defined using the Refractive Error Study in Children spherical equivalent refractive error standard of <=-0.5 diopters [D]) among the students without established myopia at baseline. Secondary outcome measures were changes in spherical equivalent refraction and axial length among all students, analyzed using mixed linear models and intention-to-treat principles. Data from the right eyes were used for the analysis. RESULTS: There were 952 children in the intervention group and 951 in the control group with a mean (SD) age of 6.6 (0.34) years. The cumulative incidence rate of myopia was 30.4% in the intervention group (259 incident cases among 853 eligible participants) and 39.5% (287 incident cases among 726 eligible participants) in the control group (difference of -9.1% [95% CI, -14.1% to -4.1%]; P < .001). There was also a significant difference in the 3-year change in spherical equivalent refraction for the intervention group (-1.42 D) compared with the control group (-1.59 D) (difference of 0.17 D [95% CI, 0.01 to 0.33 D]; P = .04). Elongation of axial length was not significantly different between the intervention group (0.95 mm) and the control group (0.98 mm) (difference of -0.03 mm [95% CI, -0.07 to 0.003 mm]; P = .07). CONCLUSIONS AND RELEVANCE: Among 6-year-old children in Guangzhou, China, the addition of 40 minutes of outdoor activity at school compared with usual activity resulted in a reduced incidence rate of myopia over the next 3 years. Further studies are needed to assess long-term follow-up of these children and the generalizability of these findings. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00848900. PMID- 26372584 TI - Sex Differences in Academic Rank in US Medical Schools in 2014. AB - IMPORTANCE: The proportion of women at the rank of full professor in US medical schools has not increased since 1980 and remains below that of men. Whether differences in age, experience, specialty, and research productivity between sexes explain persistent disparities in faculty rank has not been studied. OBJECTIVE: To analyze sex differences in faculty rank among US academic physicians. DESIGN, SETTING, AND PARTICIPANTS: We analyzed sex differences in faculty rank using a cross-sectional comprehensive database of US physicians with medical school faculty appointments in 2014 (91,073 physicians; 9.1% of all US physicians), linked to information on physician sex, age, years since residency, specialty, authored publications, National Institutes of Health (NIH) funding, and clinical trial investigation. We estimated sex differences in full professorship, as well as a combined outcome of associate or full professorship, adjusting for these factors in a multilevel (hierarchical) model. We also analyzed how sex differences varied with specialty and whether differences were more prevalent at schools ranked highly in research. EXPOSURES: Physician sex. MAIN OUTCOMES AND MEASURES: Academic faculty rank. RESULTS: In all, there were 30,464 women who were medical faculty vs 60,609 men. Of those, 3623 women (11.9%) vs 17,354 men (28.6%) had full-professor appointments, for an absolute difference of -16.7% (95% CI, -17.3% to -16.2%). Women faculty were younger and disproportionately represented in internal medicine and pediatrics. The mean total number of publications for women was 11.6 vs 24.8 for men, for a difference of -13.2 (95% CI, -13.6 to -12.7); the mean first- or last-author publications for women was 5.9 vs 13.7 for men, for a difference of -7.8 (95% CI, -8.1 to 7.5). Among 9.1% of medical faculty with an NIH grant, 6.8% (2059 of 30,464) were women and 10.3% (6237 of 60,609) were men, for a difference of -3.5% (95% CI, 3.9% to -3.1%). In all, 6.4% of women vs 8.8% of men had a trial registered on ClinicalTrials.gov, for a difference of -2.4% (95% CI, -2.8% to -2.0%). After multivariable adjustment, women were less likely than men to have achieved full professor status (absolute adjusted difference in proportion, -3.8%; 95% CI, 4.4% to -3.3%). Sex-differences in full professorship were present across all specialties and did not vary according to whether a physician's medical school was ranked highly in terms of research funding. CONCLUSIONS AND RELEVANCE: Among physicians with faculty appointments at US medical schools, there were sex differences in academic faculty rank, with women substantially less likely than men to be full professors, after accounting for age, experience, specialty, and measures of research productivity. PMID- 26372586 TI - Negotiating the Tensions in Patient-Centered Care. PMID- 26372585 TI - Outcomes After Hip Fracture Surgery Compared With Elective Total Hip Replacement. AB - IMPORTANCE: Patients undergoing surgery for a hip fracture have a higher risk of mortality and major complications compared with patients undergoing an elective total hip replacement (THR) operation. The effect of older age and comorbidities associated with hip fracture on this increased perioperative risk is unknown. OBJECTIVE: To determine if there was a difference in hospital mortality among patients who underwent hip fracture surgery relative to an elective THR, after adjustment for age, sex, and preoperative comorbidities. DESIGN, SETTING, AND PARTICIPANTS: Using the French National Hospital Discharge Database from January 2010 to December 2013, patients older than 45 years undergoing hip surgery at French hospitals were included. The International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10), codes were used to determine patients' comorbidities and complications after surgery. A population matched for age, sex, and preoperative comorbidities of patients who underwent elective THR or hip fracture surgery was created using a multivariable logistic model and a greedy matching algorithm with a 1:1 ratio. EXPOSURE: Hip fracture. MAIN OUTCOMES AND MEASURES: Postoperative in-hospital mortality. RESULTS: A total of 690,995 eligible patients were included from 864 centers in France. Patients undergoing elective THR surgery (n = 371,191) were younger, more commonly men, and had less comorbidity compared with patients undergoing hip fracture surgery. Following hip fracture surgery (n = 319,804), 10,931 patients (3.42%) died before hospital discharge and 669 patients (0.18%) died after elective THR. Multivariable analysis of the matched populations (n = 234,314) demonstrated a higher risk of mortality (1.82% for hip fracture surgery vs 0.31% for elective THR; absolute risk increase, 1.51% [95% CI, 1.46%-1.55%]; relative risk [RR], 5.88 [95% CI, 5.26-6.58]; P < .001) and of major postoperative complications (5.88% for hip fracture surgery vs 2.34% for elective THR; absolute risk increase, 3.54% [95% CI, 3.50%-3.59%]; RR, 2.50 [95% CI, 2.40-2.62]; P < .001) among patients undergoing hip fracture surgery. CONCLUSIONS AND RELEVANCE: In a large cohort of French patients, hip fracture surgery compared with elective THR was associated with a higher risk of in-hospital mortality after adjustment for age, sex, and measured comorbidities. Further studies are needed to define the causes for these differences. PMID- 26372587 TI - A Growing Scar on the Abdomen of a Middle-aged Woman. PMID- 26372588 TI - Thrombocytosis. PMID- 26372589 TI - Sex Differences in Institutional Support for Junior Biomedical Researchers. PMID- 26372590 TI - Amyloid Pathology, Cognitive Impairment, and Alzheimer Disease Risk. PMID- 26372591 TI - Amyloid Pathology, Cognitive Impairment, and Alzheimer Disease Risk--Reply. PMID- 26372592 TI - Inclusion of Physicians in Bundled Hospital Payments. PMID- 26372593 TI - Inclusion of Physicians in Bundled Hospital Payments--Reply. PMID- 26372595 TI - Misspelled Name. PMID- 26372594 TI - Incorect Spending Figure in an Editorial. PMID- 26372596 TI - Author's Middle Initials Missing in Byline. PMID- 26372597 TI - Authors' Names Reversed. PMID- 26372599 TI - Lasker Awards: Statement by the Albert and Mary Lasker Foundation. PMID- 26372600 TI - JAMA PATIENT PAGE. Teens and Sexual Abuse. PMID- 26372601 TI - Psychophysical Investigations into the Role of Low-Threshold C Fibres in Non Painful Affective Processing and Pain Modulation. AB - We recently showed that C low-threshold mechanoreceptors (CLTMRs) contribute to touch-evoked pain (allodynia) during experimental muscle pain. Conversely, in absence of ongoing pain, the activation of CLTMRs has been shown to correlate with a diffuse sensation of pleasant touch. In this study, we evaluated (1) the primary afferent fibre types contributing to positive (pleasant) and negative (unpleasant) affective touch and (2) the effects of tactile stimuli on tonic muscle pain by varying affective attributes and frequency parameters. Psychophysical observations were made in 10 healthy participants. Two types of test stimuli were applied: stroking stimulus using velvet or sandpaper at speeds of 0.1, 1.0 and 10.0 cm/s; focal vibrotactile stimulus at low (20 Hz) or high (200 Hz) frequency. These stimuli were applied in the normal condition (i.e. no experimental pain) and following the induction of muscle pain by infusing hypertonic saline (5%) into the tibialis anterior muscle. These observations were repeated following the conduction block of myelinated fibres by compression of sciatic nerve. In absence of muscle pain, all participants reliably linked velvet stroking to pleasantness and sandpaper-stroking to unpleasantness (no pain). Likewise, low-frequency vibration was linked to pleasantness and high-frequency vibration to unpleasantness. During muscle pain, the application of previously pleasant stimuli resulted in overall pain relief, whereas the application of previously unpleasant stimuli resulted in overall pain intensification. These effects were significant, reproducible and persisted following the blockade of myelinated fibres. Taken together, these findings suggest the role of low threshold C fibres in affective and pain processing. Furthermore, these observations suggest that temporal coding need not be limited to discriminative aspects of tactile processing, but may contribute to affective attributes, which in turn predispose individual responses towards excitatory or inhibitory modulation of pain. PMID- 26372602 TI - Moving Beyond Directly Observed Therapy for Tuberculosis. PMID- 26372603 TI - First bite syndrome: Our experience with intraparotid injections with botulinum toxin type A. AB - OBJECTIVES/HYPOTHESIS: First bite syndrome is the sudden onset of acute and severe pain in the parotid region at the initiation of mastication. Although it generally lasts less than a minute, it is disabling for these individuals and leads to a fear of oral intake. It is typically seen after parapharyngeal or deep parotid space surgery. Intraparotid injection of botulinum toxin A (BTA) has been suggested as a treatment for this condition, but there is little supporting literature to this effect. The purpose of this study is to document our experience using this treatment method for first bite syndrome. STUDY DESIGN: Retrospective case review. METHODS: Five patients with first bite syndrome, developed after parapharyngeal space surgery, were treated by multisite injection of BTA into the parotid gland. Between 17.5 and 50 total U of BTA were injected into four or more sites in the parotid region. The patients were then followed up every 4 months. RESULTS: Three of five patients reported a significant improvement in symptoms at the 4-month follow-up visit, although complete resolution was not reported. One patient reported only moderate improvement, and despite two series of injections there was no improvement in one patient, leading us to question our initial diagnosis. CONCLUSIONS: Unilateral BTA injection into the affected parotid gland produces a decrease in the severity of symptoms. It is a safe and viable noninvasive treatment for this difficult to treat condition and may lead to permanent resolution of symptoms in some patients. PMID- 26372605 TI - Synthesis and investigation of intra-molecular charge transfer state properties of novel donor-acceptor-donor pyridine derivatives: the effects of temperature and environment on molecular configurations and the origin of delayed fluorescence. AB - A novel series of donor-acceptor-donor (D-A-D) structured pyridine derivatives were synthesised and detailed photo-physical investigations were made using mainly steady-state and time-resolved spectroscopy techniques at varying temperatures. The investigations showed that the molecules have solvent polarity and temperature dependent excited-state configurations, confirmed in two different polarity solvents (295-90 K), i.e. methyl cyclohexane (MCH) and 2 methyltetrahdrofurane (2-MeTHF). In MCH, the investigations revealed dual fluorescence over the temperature range of 295-90 K. At 295 K, the ground-state configuration of the molecules has a partially twisted geometry as determined by DFT calculation, yet the emission originates totally from a locally excited (LE) state, however once the temperature is lowered to 90 K, the twisted molecular configuration is stabilised, and the emission originates from a fully-relaxed intramolecular charge transfer state (ICT), this is contrary to the systems where structural reorganisation stabilises ICT and this is frozen out at low temperatures. The DFT calculations revealed different ground state molecular configurations due to the presence of different electron-donating groups, e.g. the molecule including anthracene groups has a near 90 degrees twisted geometry whereas the triphenylamine including molecule has a pyramidal geometrical folding, therefore, the decrease in temperature restricts the donor degree of rotational freedom. In 2-MeTHF solution, the fluorescence spectrum of both molecules is always of ICT character, but gradually red-shifts through the fluid to glass transition temperature (~135 K), in this case, the fluorescence occurs after structural and solvent-shell relaxations, however, upon cooling below 135 K, the spectra dramatically shift back to blue giving rise to strong emission from an ICT excited-state (but not the LE state) where the molecules have unrelaxed geometries. This significant change in the nature of the emitting species was explained with specific solvent-solute dynamic interactions in the vicinity of the solvation shell and the effect of thermal excitation of molecular vibrational modes of the C-C bond linking donor and acceptor units. Finally, we confirmed that the molecules have ICT ground-state geometry in the solid-state phase (spin-coated films), and the time-resolved decay dynamics were investigated comparing the spin-coated films (at RT and 25 K) and MCH solutions (at 295 K and 90 K). PMID- 26372604 TI - Repetitive DNA Sequences and Evolution of ZZ/ZW Sex Chromosomes in Characidium (Teleostei: Characiformes). AB - Characidium constitutes an interesting model for cytogenetic studies, since a large degree of karyotype variation has been detected in this group, like the presence/absence of sex and supernumerary chromosomes and variable distribution of repetitive sequences in different species/populations. In this study, we performed a comparative cytogenetic analysis in 13 Characidium species collected at different South American river basins in order to investigate the karyotype diversification in this group. Chromosome analyses involved the karyotype characterization, cytogenetic mapping of repetitive DNA sequences and cross species chromosome painting using a W-specific probe obtained in a previous study from Characidium gomesi. Our results evidenced a conserved diploid chromosome number of 2n = 50, and almost all the species exhibited homeologous ZZ/ZW sex chromosomes in different stages of differentiation, except C. cf. zebra, C. tenue, C. xavante and C. stigmosum. Notably, some ZZ/ZW sex chromosomes showed 5S and/or 18S rDNA clusters, while no U2 snDNA sites could be detected in the sex chromosomes, being restricted to a single chromosome pair in almost all the analyzed species. In addition, the species Characidium sp. aff. C. vidali showed B chromosomes with an inter-individual variation of 1 to 4 supernumerary chromosomes per cell. Notably, these B chromosomes share sequences with the W specific probe, providing insights about their origin. Results presented here further confirm the extensive karyotype diversity within Characidium in contrast with a conserved diploid chromosome number. Such chromosome differences seem to constitute a significant reproductive barrier, since several sympatric Characidium species had been described during the last few years and no interespecific hybrids were found. PMID- 26372606 TI - Changes in the human plasma and urinary metabolome associated with acute dietary exposure to sucrose and the identification of potential biomarkers of sucrose intake. AB - SCOPE: The intake of sucrose is of public health concern but limited information is available on the metabolic effects of short-term exposure. Our aim was to use metabolomics to investigate the metabolic impact of acute sucrose exposure. METHODS AND RESULTS: We performed a randomized, parallel, single-dose feeding study on healthy females (n = 90, aged 29.9 +/- 4.7 years, BMI 23.3 +/- 2.5 kg/m(2) ) consuming either 0, 50, or 100 g sucrose in 500 mL water. Blood and urine samples were taken before and 24 h post sucrose intake. Urine and plasma samples underwent detailed metabolite profiling analysis using established protocols. Flow-injection electrospray MS fingerprinting analysis showed that 3 h after intake was the most informative time point in urine and plasma and out of 120 explanatory signals, highlighted 16 major metabolite signals in urine and 25 metabolite signals in plasma that were discriminatory and correlated with sucrose intake over time. The main confirmed metabolites positively correlated with intake were sucrose, fructose, and erythronic acid, while those negatively correlating with intake included fatty acids and derivatives, acyl-carnitines, and ketone bodies. GC-TOF-MS profiling analysis confirmed the fingerprinting data. CONCLUSION: Acute exposure to sucrose identified a number of metabolites correlated with sucrose intake and several compounds attributed to metabolic fasting. PMID- 26372607 TI - A pilot and feasibility study of the plasma and tissue pharmacokinetics of cefazolin in an immature porcine model of pediatric cardiac surgery. AB - BACKGROUND: Surgical site infection (SSI) prevention for children with congenital heart disease is imperative and methods to assess and evaluate the tissue concentrations of prophylactic antibiotics are important to help maximize these efforts. AIM: The purposes of this study were to determine the plasma and tissue concentrations with standard of care, perioperative cefazolin dosing in an immature porcine model of pediatric cardiac surgery, and to determine the feasibility of this model. METHODS: Piglets (3-5 days old) underwent either median sternotomy (MS) or cardiopulmonary bypass with deep hypothermic circulatory arrest (CPB + DHCA) and received standard of care prophylactic cefazolin for the procedures. Serial plasma and microdialysis sampling of the skeletal muscle and subcutaneous tissue adjacent to the surgical site was performed. Cefazolin concentrations were measured, noncompartmental pharmacokinetic analyses were performed, and tissue penetration of cefazolin was assessed. RESULTS: Following the first intravenous dose, maximal cefazolin concentrations in the subcutaneous tissue and skeletal muscle were similar between groups with peak tissue concentrations 15-30 min after administration. After the second cefazolin dose given with the initiation of CPB, total plasma cefazolin concentrations remained relatively constant until the end of DHCA and then decreased while muscle- and subcutaneous-unbound cefazolin concentrations showed a second peak during or after rewarming. For the MS group, 60-67% of the intraoperative time showed subcutaneous and skeletal muscle concentrations of cefazolin >16 MUg.ml(-1) while this percentage was 78-79% for the CPB + DHCA group. There was less tissue penetration of cefazolin in the group that underwent CBP + DHCA (P = 0.03). CONCLUSIONS: The cefazolin dosing used in this study achieves plasma and tissue concentrations that should be effective against methicillin-sensitive Staphylococcus aureus but may not be effective against some gram-negative pathogens. The timing of the cefazolin administration prior to incision and a second dose given during cardiopulmonary bypass may be important factors for achieving goal tissue concentrations. PMID- 26372608 TI - Feasibility of a facile butanol bioproduction using planetary mill pretreatment. AB - A facile butanol bioproduction process was developed using planetary milling, and Pinus rigida wood waste as a model substrate for fermentable sugars. The use of planetary milling as the pretreatment eliminates the need for washing and transfer of the biomass prior to enzymatic hydrolysis. Moreover, using this pretreatment process resulted in the production of only 0.072 +/- 0.003 g/L soluble phenolic compounds, a concentration that was not inhibitory towards Clostridium beijerinckii NCIMB 8052. As the milling was performed in a compatible buffer (50mM acetate, pH 4.8), the enzymatic hydrolysis step was initiated by simply adding the cellulase cocktail powder directly to pretreated biomass without washing the biomass or exchanging the buffer, resulting in a glucose yield of 31 g/L (84.02%). Fermentation of the hydrolysate samples by C. beijerinckii NCIMB 8052 gave slightly better butanol yields than cultures grown in a typical lab media (P2), with final concentrations of 6.91 and 6.66 g/L, respectively. PMID- 26372609 TI - Factors defining the mentoring competencies of clinical midwives: An exploratory quantitative research study in Japan. AB - BACKGROUND: Clinical education is an extremely important process in cultivating healthcare professionals, and the quality of educators has a major impact on the quality of future practitioners. Although practicing clinical midwives contribute to the education of pre-registered midwives and those qualified within the past year (new midwives), the factors defining the educational competencies of clinical midwives have not been clarified. OBJECTIVES: The purpose of this study was to explore the factors that define the mentoring competencies of clinical midwives involved in educating new midwives. DESIGN: An exploratory quantitative research study. METHODS: Questionnaires were distributed to 694 midwives who had previously conducted educational activities with new midwives at the 63 facilities whose administrator or nurse manager in charge of all staff, including midwives, consented to participate. Of the 694 midwives, 464 (66.9%) returned the questionnaire and 451 (65.1%) valid responses were analyzed. Exploratory factor analyses were performed on the following three concepts: [competency as a professional], [competency as an educator], and [personal characteristics]. RESULTS: [Competency as a professional] consisted of two factors: and ; [competency as an educator] consisted of four factors: , , and ; and [personal characteristics consisted of three factors: , and . These three concepts were defined by a total of nine sub-concepts (factors), and 41 items were extracted with a reliability coefficient (Cronbach's alpha) of 0.944 CONCLUSIONS: "Mentoring competencies of clinical midwives (MCCM)" are defined by three concepts and nine sub-concepts, which can be evaluated by 41 items regarding the behavior, thoughts, and characteristics that clinical midwives exhibit when they educate new midwives in clinical settings. PMID- 26372610 TI - Evaluation of how a curriculum change in nurse education was managed through the application of a business change management model: A qualitative case study. AB - BACKGROUND: Curriculum changes are a regular feature of nurse education, yet little is known about how such changes are managed. Research in this arena is yet to emerge. OBJECTIVE: Evaluation of how a curriculum change in nurse education was managed through the application of a business change management model. METHOD: A qualitative case study: the single case was the new curriculum, the Primary Care Pathway. PARTICIPANTS AND SETTING: One executive, three senior managers, two academics and nineteen students participated in this study in one faculty of health and social care in a higher education institution. RESULTS: The findings suggest that leadership was pivotal to the inception of the programme and guiding teams managed the change and did not take on a leadership role. The vision for the change and efforts to communicate it did not reach the frontline. Whilst empowerment was high amongst stakeholders and students, academics felt dis empowered. Short-term wins were not significant in keeping up the momentum of change. The credibility of the change was under challenge and the concept of the new programme was not yet embedded in academia. CONCLUSION: Differences between the strategic and operational part of the organisation surfaced with many challenges occurring at the implementation stage. The business change model used was valuable, but was found to not be applicable during curriculum changes in nurse education. A new change model emerged, and a tool was developed alongside to aid future curriculum changes. PMID- 26372611 TI - Translocation of threatened plants as a conservation measure in China. AB - We assessed the current status of plant conservation translocation efforts in China, a topic poorly reported in recent scientific literature. We identified 222 conservation translocation cases involving 154 species, of these 87 were Chinese endemic species and 101 (78%) were listed as threatened on the Chinese Species Red List. We categorized the life form of each species and, when possible, determined for each case the translocation type, propagule source, propagule type, and survival and reproductive parameters. A surprisingly large proportion (26%) of the conservation translocations in China were conservation introductions, largely implemented in response to large-scale habitat destruction caused by the Three-Gorge Dam and another hydropower project. Documentation and management of the translocations varied greatly. Less than half the cases had plant survival records. Statistical analyses showed that survival percentages were significantly correlated with plant life form and the type of planting materials. Thirty percent of the cases had records on whether or not individuals flowered or fruited. Results of information theoretic model selection indicated that plant life form, translocation type, propagule type, propagule source, and time since planting significantly influenced the likelihood of flowering and fruiting on the project level. We suggest that the scientific-based application of species conservation translocations should be promoted as part of a commitment to species recovery management. In addition, we recommend that the common practice of within and out of range introductions in nature reserves to be regulated more carefully due to its potential ecological risks. We recommend the establishment of a national office and database to coordinate conservation translocations in China. Our review effort is timely considering the need for a comprehensive national guideline for the newly announced nation-wide conservation program on species with extremely small populations, which is expected to stimulate conservation translocations for many species in the near future. PMID- 26372613 TI - Sediment transport in two mediterranean regulated rivers. AB - Mediterranean climate is characterized by highly irregular rainfall patterns with marked differences between wet and dry seasons which lead to highly variable hydrological fluvial regimes. As a result, and in order to ensure water availability and reduce its temporal variability, a high number of large dams were built during the 20th century (more than 3500 located in Mediterranean rivers). Dams modify the flow regime but also interrupt the continuity of sediment transfer along the river network, thereby changing its functioning as an ecosystem. Within this context, the present paper aims to assess the suspended sediment loads and dynamics of two climatically contrasting Mediterranean regulated rivers (i.e. the Esera and Siurana) during a 2-yr period. Key findings indicate that floods were responsible for 92% of the total suspended sediment load in the River Siurana, while this percentage falls to 70% for the Esera, indicating the importance of baseflows on sediment transport in this river. This fact is related to the high sediment availability, with the Esera acting as a non supply-limited catchment due to the high productivity of the sources (i.e. badlands). In contrast, the Siurana can be considered a supply-limited system due to its low geomorphic activity and reduced sediment availability, with suspended sediment concentration remaining low even for high magnitude flood events. Reservoirs in both rivers reduce sediment load up to 90%, although total runoff is only reduced in the case of the River Esera. A remarkable fact is the change of the hydrological character of the River Esera downstream for the dam, shifting from a humid mountainous river regime to a quasi-invariable pattern, whereas the Siurana experiences the opposite effect, changing from a flashy Mediterranean river to a more constant flow regime below the dam. PMID- 26372612 TI - Facial nerve stimulation in the narrow bony cochlear nerve canal after cochlear implantation. AB - OBJECTIVES/HYPOTHESIS: To evaluate the correlation between a narrow bony cochlear nerve canal (BCNC) and facial nerve stimulation (FNS) after cochlear implantation (CI) and their underlying mechanisms and to predict the risk of FNS preoperatively. STUDY DESIGN: Retrospective cohort study. METHODS: A total of 64 pediatric cases that underwent CI were included. Among them, 32 cases experienced FNS after CI, and another 32 cases were selected from 817 pediatric implantees by stratified random sampling. The width of the BCNC, the status of the cochlear nerve (CN) and the internal auditory canal (IAC), T level, and C level were compared and analyzed. Strategies for eliminating FNS were also analyzed. RESULTS: The FNS group showed a narrower BCNC (1.09 +/- 0.52 mm) than the control group (1.99 +/- 0.61 mm; P < .01), a lower CN/facial nerve ratio (0.32 +/- 0.36) than the control group (1.34 +/- 0.76; P < .01), and narrower IAC diameter (4.06 +/- 1.71 mm) than the control group (5.66 +/- 1.36 mm; P < .01). The FNS group also showed higher T level (165.7 +/- 28.3 MUA) than the control group (142.2 +/- 21.2 MUA; P < .01). Adjustment of the C levels and/or pulse width and switching off offending electrodes were attempted to eliminate FNS, with a 75.0% success rate. The FNS group still showed low Categories of Auditory Performance scores (3.00 +/- 1.90) compared with the control group (5.94 +/- 1.41, P < .01) after adjustment. CONCLUSIONS: A narrow BCNC could be a cause of FNS after CI. Therefore, careful selection of the side for CI and programming strategies are required to reduce FNS. LEVEL OF EVIDENCE: 4. Laryngoscope, 126:1433-1439, 2016. PMID- 26372614 TI - Discovering Recurrent Copy Number Aberrations in Complex Patterns via Non Negative Sparse Singular Value Decomposition. AB - Recurrent copy number aberrations (RCNAs) in multiple cancer samples are strongly associated with tumorigenesis, and RCNA discovery is helpful to cancer research and treatment. Despite the emergence of numerous RCNA discovering methods, most of them are unable to detect RCNAs in complex patterns that are influenced by complicating factors including aberration in partial samples, co-existing of gains and losses and normal-like tumor samples. Here, we propose a novel computational method, called non-negative sparse singular value decomposition (NN SSVD), to address the RCNA discovering problem in complex patterns. In NN-SSVD, the measurement of RCNA is based on the aberration frequency in a part of samples rather than all samples, which can circumvent the complexity of different RCNA patterns. We evaluate NN-SSVD on synthetic dataset by comparison on detection scores and Receiver Operating Characteristics curves, and the results show that NN-SSVD outperforms existing methods in RCNA discovery and demonstrate more robustness to RCNA complicating factors. Applying our approach on a breast cancer dataset, we successfully identify a number of genomic regions that are strongly correlated with previous studies, which harbor a bunch of known breast cancer associated genes. PMID- 26372615 TI - Foot-controlled robotic-enabled endoscope holder for endoscopic sinus surgery: A cadaveric feasibility study. AB - OBJECTIVES/HYPOTHESIS: To evaluate the feasibility of a unique prototype foot controlled robotic-enabled endoscope holder (FREE) in functional endoscopic sinus surgery. STUDY DESIGN: Cadaveric study. METHODS: Using human cadavers, we investigated the feasibility, advantages, and disadvantages of the robotic endoscope holder in performing endoscopic sinus surgery with two hands in five cadaver heads, mimicking a single nostril three-handed technique. RESULTS: The FREE robot is relatively easy to use. Setup was quick, taking less than 3 minutes from docking the robot at the head of the bed to visualizing the middle meatus. The unit is also relatively small, takes up little space, and currently has four degrees of freedom. The learning curve for using the foot control was short. The use of both hands was not hindered by the presence of the endoscope in the nasal cavity. The tremor filtration also aided in the smooth movement of the endoscope, with minimal collisions. CONCLUSION: The FREE endoscope holder in an ex-vivo cadaver test corroborated the feasibility of the robotic prototype, which allows for a two-handed approach to surgery equal to a single nostril three-handed technique without the holder that may reduce operating time. Further studies will be needed to evaluate its safety profile and use in other areas of endoscopic surgery. LEVEL OF EVIDENCE: NA. Laryngoscope, 126:566-569, 2016. PMID- 26372617 TI - Abstracts of the 39th European Congress of Cytopathology, Milan, Italy, 20 - 23 September 2015. PMID- 26372616 TI - [Anti-inflammatory drugs and community-acquired pneumonia]. AB - Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used in ambulatory medicine for their analgesic and antipyretic properties and are often used as self-medication. Their use in community-acquired pneumonia is associated with an increased risk of loco-regional complications, especially pleural empyema. Appropriate therapeutic care and hospital admissions are often delayed because of initial improvement of symptoms with NSAIDs. Despite worrying observational data, a causal link remains to be established. Currently, there is no recommendation cautioning against the use of NSAIDs in the management of community-acquired pneumonia. PMID- 26372618 TI - World-class expertise: a developmental model. AB - The field of psychology has done a remarkable job discovering the ways people differ from one another in their abilities and talents, but has long neglected the diverse ways people can unleash those capacities. There is no plausible mechanism by which our genes directly encode skills like how to dribble a basketball, play the violin, or solve an algebraic equation. We are not born knowing how to write a sonnet or flip an omelet. On the contrary, all human expertise-even at the far-right tail of the distribution-depends on experience and training. A more accurate understanding of the development of high achievement should inspire people to push beyond their perceived and often self imposed limits to reach heights they never would have imagined possible. WIREs Cogn Sci 2017, 8:e1365. doi: 10.1002/wcs.1365 For further resources related to this article, please visit the WIREs website. PMID- 26372619 TI - Medication adherence decision-making among adolescents and young adults with cancer. AB - PURPOSE: Nearly half of all adolescents and young adults (AYAs) with cancer struggle to adhere to oral chemotherapy or antibiotic prophylactic medication included in treatment protocols. The mechanisms that drive non-adherence remain unknown, leaving health care providers with few strategies to improve adherence among their patients. The purpose of this study was to use qualitative methods to investigate the mechanisms that drive the daily adherence decision-making process among AYAs with cancer. METHODS: Twelve AYAs (ages 15-31) with cancer who had a current medication regimen that included oral chemotherapy or antibiotic prophylactic medication participated in this study. Adolescents and young adults completed a semi-structured interview and a card sorting task to elucidate the themes that impact adherence decision-making. Interviews were transcribed verbatim and coded twice by two independent raters to identify key themes and develop an overarching theoretical framework. RESULTS: Adolescents and young adults with cancer described adherence decision-making as a complex, multi dimensional process influenced by personal goals and values, knowledge, skills, and environmental and social factors. Themes were generally consistent across medication regimens but differed with age, with older AYAs discussing long-term impacts and receiving physical support from their caregivers more than younger AYAs. CONCLUSIONS: The mechanisms that drive daily adherence decision-making among AYAs with cancer are consistent with those described in empirically supported models of adherence among adults with other chronic medical conditions. These mechanisms offer several modifiable targets for health care providers striving to improve adherence among this vulnerable population. PMID- 26372620 TI - Targeted Muscle Reinnervation of the Brachium: An Anatomic Study of Musculocutaneous and Radial Nerve Motor Points Relative to Proximal Landmarks. AB - PURPOSE: Targeted muscle reinnervation (TMR) offers enhanced prosthetic use by harnessing additional neural control from unused nerves in the amputated limb. The purpose of this study was to document the location and number of motor end plates to each muscle commonly used in TMR in the brachium relative to proximally based bony landmarks. METHODS: We dissected 18 matched upper limbs (9 fresh frozen cadavers). The locations of each of the nerves' muscular insertions into the medial biceps and brachialis were measured relative to the anterolateral tip of the acromion. The terminal branches to the lateral triceps were measured relative to the posterolateral tip of the acromion. Both the number of branches and the location of the muscular insertions were documented. Common descriptive statistics were used to describe the data. RESULTS: There was a median of 2 branches to the medial biceps located 19.6 cm from the anterolateral tip of the acromion (range, 15-25 cm). There was a median of 3.5 branches to the brachialis located 24.2 cm from the anterolateral tip of the acromion (range, 19-27.5 cm). There was a median of 2.5 branches to the lateral triceps located 21.6 cm from the posterolateral tip of the acromion (range, 11-29 cm). The mean distances to the primary branch muscle and the number of smaller branches were not significantly different when compared by sex or side. CONCLUSIONS: Motor points for the medial biceps, brachialis, and lateral triceps can be identified reliably using proximal landmarks in targeted muscle reinnervation. CLINICAL RELEVANCE: The data obtained from this study may assist the surgeon in localizing the nerve branches and muscular insertions for the commonly used muscles for TMR of the brachium. PMID- 26372621 TI - Quality Measurements in Radiology: A Systematic Review of the Literature and Survey of Radiology Benefit Management Groups. AB - PURPOSE: As the US health care system transitions toward value-based reimbursement, there is an increasing need for metrics to quantify health care quality. Within radiology, many quality metrics are in use, and still more have been proposed, but there have been limited attempts to systematically inventory these measures and classify them using a standard framework. The purpose of this study was to develop an exhaustive inventory of public and private sector imaging quality metrics classified according to the classic Donabedian framework (structure, process, and outcome). METHODS: A systematic review was performed in which eligibility criteria included published articles (from 2000 onward) from multiple databases. Studies were double-read, with discrepancies resolved by consensus. For the radiology benefit management group (RBM) survey, the six known companies nationally were surveyed. Outcome measures were organized on the basis of standard categories (structure, process, and outcome) and reported using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: The search strategy yielded 1,816 citations; review yielded 110 reports (29 included for final analysis). Three of six RBMs (50%) responded to the survey; the websites of the other RBMs were searched for additional metrics. Seventy-five unique metrics were reported: 35 structure (46%), 20 outcome (27%), and 20 process (27%) metrics. For RBMs, 35 metrics were reported: 27 structure (77%), 4 process (11%), and 4 outcome (11%) metrics. The most commonly cited structure, process, and outcome metrics included ACR accreditation (37%), ACR Appropriateness Criteria (85%), and peer review (95%), respectively. CONCLUSIONS: Imaging quality metrics are more likely to be structural (46%) than process (27%) or outcome (27%) based (P < .05). As national value-based reimbursement programs increasingly emphasize outcome-based metrics, radiologists must keep pace by developing the data infrastructure required to collect outcome-based quality metrics. PMID- 26372622 TI - Elevated excretion of biopyrrin as a new marker for idiopathic Parkinson's disease. PMID- 26372623 TI - Non-motor symptoms in Parkinson's disease. AB - With the growing awareness of the presence of non-motor symptoms in Parkinson's disease (PD) has come the realization that these non-motor features play a tremendously important, and sometimes dominant, role in the management and even the diagnosis of the disorder. Despite this, a reluctance to formally address and treat the non-motor symptoms of PD remains and quality of life for PD patients suffers. This review provides an overview of the impact non-motor symptoms have on persons with PD, along with a brief description of some of the more common non motor features of PD. PMID- 26372624 TI - Normal substantia nigra patients treated with levodopa - Clinical, therapeutic and pathological observations. AB - BACKGROUND: Definite diagnosis of idiopathic Parkinson's disease is based on histological findings of marked substantia nigra neuronal loss and Lewy body inclusions. Almost all cases with clinical diagnosis of idiopathic Parkinson's disease are treated with levodopa. Because there is no biological marker for the diagnosis, erroneous clinical diagnosis and treatment of such cases with levodopa are well known. There is very limited literature on levodopa treated cases that had normal substantia nigra at autopsy. METHODS: Patients seen at Movement Disorders Clinic Saskatchewan are offered autopsy at no cost to the family/estate of the patient. Autopsy studies are performed by certified neuropathologists. Notation on the status of substantia nigra is made in every autopsied case. RESULTS: Between 1968 and 2014, 21 cases treated with levodopa had normal substantia nigra at autopsy. Eleven patients continued levodopa until death and 9 received the drug for four years or longer. No objective motor symptom benefit, dyskinesia or motor response fluctuations on levodopa were observed in any case. The most common final diagnosis was essential tremor. CONCLUSION: Individuals with normal substantia nigra do not benefit from levodopa and do not manifest motor response fluctuations or dyskinesia. Long-term use of levodopa is not toxic to normal human substantia nigra. PMID- 26372625 TI - Interaction between basal ganglia and limbic circuits in learning and memory processes. AB - Hippocampus and striatum play distinctive roles in memory processes since declarative and non-declarative memory systems may act independently. However, hippocampus and striatum can also be engaged to function in parallel as part of a dynamic system to integrate previous experience and adjust behavioral responses. In these structures the formation, storage, and retrieval of memory require a synaptic mechanism that is able to integrate multiple signals and to translate them into persistent molecular traces at both the corticostriatal and hippocampal/limbic synapses. The best cellular candidate for this complex synthesis is represented by long-term potentiation (LTP). A common feature of LTP expressed in these two memory systems is the critical requirement of convergence and coincidence of glutamatergic and dopaminergic inputs to the dendritic spines of the neurons expressing this form of synaptic plasticity. In experimental models of Parkinson's disease abnormal accumulation of alpha-synuclein affects these two memory systems by altering two major synaptic mechanisms underlying cognitive functions in cholinergic striatal neurons, likely implicated in basal ganglia dependent operative memory, and in the CA1 hippocampal region, playing a central function in episodic/declarative memory processes. PMID- 26372626 TI - Effects of posterior ridge resorption and attachment wear on periimplant strain in mandibular two-implant-supported overdentures. AB - STATEMENT OF PROBLEM: Progressive resorption of the posterior residual ridge and attachment wear increase the rotational movement of mandibular 2-implant supported overdentures (IODs). Limited information is available regarding the biomechanical effects of rotational movement on anterior implants during mastication. PURPOSE: The purpose of this in vitro investigation was to analyze the effects of posterior ridge resorption and attachment wear, using simulated IODs to examine periimplant strain changes under dynamic loading conditions. MATERIAL AND METHODS: Two dental implants were positioned in the canine regions of a mandibular edentulous cast. Two mandibular edentulous models were fabricated from the cast by using a fixture-level impression technique, and IODs reinforced with a cobalt-chromium cast framework were prepared using the laboratory models. Two different types of stud attachments (Locator and O-ring) were connected to each paired model and to the IOD. Using a dynamic load of 100 N, continuous stress-strain changes were recorded under 3 conditions: the original condition of the paired laboratory models and the IODs, following a 1-mm reduction of the posterior residual ridge support, and after performing a fatigue test to simulate attachment wear after reduction of the posterior ridge support. After these measurements, a scanning electron microscope (SEM) was used to analyze attachment wear. RESULTS: In all implants, the 1-mm posterior ridge reduction and attachment wear procedure did not remarkably elevate tensile forces compared with their original condition. All stress-strain curves showed phased strain changes caused by the rotational movement of the IODs. After the fatigue test, the shape of the stress-strain curve changed from a smooth curve to a polygonal line compared with that in the previous records. The Locator matrices showed more wear than the other attachment components. CONCLUSIONS: Neither attachment wear nor an increase of the IOD rotational movement caused by an approximately 1-mm decrease in the posterior mucosal support led to significant changes in the periimplant strain in IODs. PMID- 26372627 TI - Effects of multiple firings on metal-ceramic bond strength of Co-Cr alloy fabricated by selective laser melting. AB - STATEMENT OF PROBLEM: Selective laser melting (SLM) is a new technique for fabricating dental restorations, but the metal-ceramic bond strength of the restorations after multiple firings must be considered because adequate bond strength is a clinical requirement for long-term performance. PURPOSE: The purpose of this study was to investigate the effects of repeated firing on the metal-ceramic bond strength of an SLM Co-Cr alloy. MATERIAL AND METHODS: Thirty six SLM-fabricated (Group SLM) and conventional lost wax cast (Group Cast) Co-Cr metal bars were prepared. Eighteen bars from each group were molded into dimensions of 25*3*0.5 mm, following International Organization for Standardization (ISO) standard 9693:2012. In the center of each bar, a 1.1-mm thickness of porcelain was fused onto an 8*3-mm rectangular area. In each group, specimens were divided into 3 subgroups based on the number of firing cycles (3, 5, 7) for the veneering process. Metal-ceramic bond strength, fracture mode analysis, and area fraction of adherence porcelain (AFAP) of each subgroup was evaluated with a 3-point bend test and by measuring the Si content of specimens with scanning electron microscopy (SEM) and energy-dispersive x-ray spectroscopy (EDS). The results were statistically analyzed first with the Shapiro-Wilk test, where a P value of .364 was considered normally distributed, and then with the Student t test to determine significant differences (alpha=.05). RESULTS: Student t test results showed no statistical differences between the metal-ceramic bond strength of SLM and that of conventionally cast groups after firing 3, 5, and 7 times (P>.05). However, after SEM/EDS analyses, the SLM group showed significantly more porcelain adherence than that of the control group (P<.05) after 5 or 7 firings. CONCLUSIONS: The SLM group showed superior metal-ceramic bond strength that exceeded ISO 9691:1999 (E) requirements at all firing periods. Also, the bond showed better behavior in terms of AFAP than the conventional cast group, especially after 5 or 7 firings. PMID- 26372628 TI - Virtual facebow technique. AB - This article describes a virtual technique for transferring the location of a digitized cast from the patient to a virtual articulator (virtual facebow transfer). Using a virtual procedure, the maxillary digital cast is transferred to a virtual articulator by means of reverse engineering devices. The following devices necessary to carry out this protocol are available in many contemporary practices: an intraoral scanner, a digital camera, and specific software. Results prove the viability of integrating different tools and software and of completely integrating this procedure into a dental digital workflow. PMID- 26372629 TI - Comparison of treatment time versus patient satisfaction in at-home and in-office tooth bleaching therapy. AB - STATEMENT OF THE PROBLEM: There are different approaches and treatment times to achieve tooth whitening. PURPOSE: The purpose of this study was to evaluate the efficacy of different agents and the treatment time required to achieve participant satisfaction with at-home and in-office tooth whitening. MATERIAL AND METHODS: Thirty participants were selected based on the shade of the anterior teeth (between A2 and A3.5; Vita Classic Shade Guide). Each participant received both in-office and at-home bleaching agents in a split-mouth design at both arches. In-office bleaching was performed in the maxillary quadrants, applying 35% hydrogen peroxide (HP35%) (right) and 35% HP with calcium (HP35%Ca) (left) for 40 minutes/week. Home bleaching was performed in mandibular quadrants using carbamide peroxide 10% (CP10%) (right) and CP22% (left) for 2 hours/day. Bleaching treatments were performed until participant satisfaction was achieved (maximum 6 sessions [S] in the dental office or 6 weeks [W] in the home). The shade was measured with a spectrophotometer before treatment, then at 2 and 4 weeks, and at the last week for at-home bleaching; and 1 week after the second, fourth, and last sessions for in-office bleaching. Student t and Tukey-Kramer tests were used (alpha=.05). RESULTS: All bleaching agents were effective for vital tooth whitening. No significant differences were observed for color changes between CP10% and CP22% or between HP35% and HP35%Ca for all periods. Treatment times required to achieve patient satisfaction for the in-office bleaching technique were 4S (12 participants), 5S (10 participants), and 6S (8 participants); and 4W (6 participants), 5W (8 participants), and 6W (16 participants) for the at-home bleaching technique. CONCLUSIONS: Treatment time to participant satisfaction ranged from 4 to 6 weeks regardless of the bleaching agent used in at-home and in-office therapy. PMID- 26372630 TI - Mandibular fibular graft reconstruction with CAD/CAM technology: A clinical report and literature review. AB - This clinical report describes the treatment of a partially dentate patient who presented with dental implants placed in a reconstructed fibula graft in the mandible. A complete mouth rehabilitation with a maxillary complete denture and a mandibular implant-supported fixed complete denture was fabricated with computer aided design and computer-aided machining technology. PMID- 26372631 TI - Controlling the depth of ceramic veneer preparations by using a color marker in the depth grooves. PMID- 26372632 TI - Monitoring Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes with Genetically Encoded Calcium and Voltage Fluorescent Reporters. AB - The advent of the human-induced pluripotent stem cell (hiPSC) technology has transformed biomedical research, providing new tools for human disease modeling, drug development, and regenerative medicine. To fulfill its unique potential in the cardiovascular field, efficient methods should be developed for high resolution, large-scale, long-term, and serial functional cellular phenotyping of hiPSC-derived cardiomyocytes (hiPSC-CMs). To achieve this goal, we combined the hiPSC technology with genetically encoded voltage (ArcLight) and calcium (GCaMP5G) fluorescent indicators. Expression of ArcLight and GCaMP5G in hiPSC-CMs permitted to reliably follow changes in transmembrane potential and intracellular calcium levels, respectively. This allowed monitoring short- and long-term changes in action-potential and calcium-handling properties and the development of arrhythmias in response to several pharmaceutical agents and in hiPSC-CMs derived from patients with different inherited arrhythmogenic syndromes. Combining genetically encoded fluorescent reporters with hiPSC-CMs may bring a unique value to the study of inherited disorders, developmental biology, and drug development and testing. PMID- 26372633 TI - Semi-manual mastoidectomy assisted by human-robot collaborative control - A temporal bone replica study. AB - OBJECTIVE: To develop an otological robot that can protect important organs from being injured. METHODS: We developed a five degree-of-freedom robot for otological surgery. Unlike the other robots that were reported previously, our robot does not replace surgeon's procedures, but instead utilizes human-robot collaborative control. The robot basically releases all of the actuators so that the surgeon can manipulate the drill within the robot's working area with minimal restriction. When the drill reaches a forbidden area, the surgeon feels as if the drill hits a wall. RESULTS: When an engineer performed mastoidectomy using the robot for assistance, the facial nerve in the segmented region was always protected with a more than 2.5mm margin, which was almost the same as the pre-set safety margin of 3mm. CONCLUSION: Semi-manual drilling using human-robot collaborative control was feasible, and may hold a realistic prospect of clinical use in the near future. PMID- 26372634 TI - Expert testimony in sexual assault cases: Alcohol intoxication and memory. AB - At court-martial tribunals in the United States military, cases involving alcohol facilitated sexual assault often pivot on the alleged victim's level of intoxication or impairment and ability to consent to the sexual act. These cases frequently arise following a night of partying and heavy drinking among a group of friends and acquaintances, military and civilian. The determination of whether a sexual act was consensual may rest on estimates of the alleged victim's blood alcohol concentration and related behavioral indicia of impairment. Expert testimony may be presented by the prosecution and/or the defense, from forensic toxicologists and psychiatrists or psychologists regarding the potential involvement of alcohol and its impact on the participants relevant to the charges at court-martial. A review of the state of the science is offered to bring such testimony into perspective. Appellate cases illustrate that the experts' testimony may sometimes elucidate, sometimes obfuscate, and sometimes exceed professional expertise and invade the province of the factfinder. PMID- 26372635 TI - Implementation of an Acute Care Surgery Service Facilitates Modern Clinical Practice Guidelines for Gallstone Pancreatitis. AB - BACKGROUND: Current practice guidelines for management of gallstone pancreatitis (GSP) recommend early cholecystectomy for patient stabilization and bile duct clearance, preferably at index admission. Historically, this has been difficult to achieve due to lack of emergency surgical resources. We investigated whether implementation of an acute care surgery (ACS) model would allow better adherence to current practice guidelines for GSP. STUDY DESIGN: A retrospective review was conducted of all patients admitted with the diagnosis of GSP to 2 tertiary care university teaching hospitals from January 2002 to October 2013. Diagnosis was confirmed on review of clinical, biochemical, and radiographic criteria. Patients were divided into pre-ACS (2002 to 2009) and post-ACS (2010 to 2013) eras. Only 1 of the 2 hospitals implemented an ACS service in the latter era. Data were collected on demographics, admissions, cholecystectomy timing, and emergency department visits. RESULTS: Before implementation of an ACS service, the rate of index cholecystectomy was 3% at both hospital sites. The rate of index cholecystectomy increased significantly with the addition of ACS, from 2.4% to 67% (p < 0.001). The presence of an ACS team was highly predictive of index cholecystectomy (odds ratio = 10.4; 95% CI 2.0 to 55.1). Patients who did not undergo cholecystectomy during the index admission had an overall readmission rate of 24.9% at both sites. In the ACS hospital, repeat emergency department visits decreased from 24.8% to 8.3% (p < 0.001) and readmission rate decreased from 16.8% to 7.3% (p = 0.04) in the pre-and post-ACS eras, respectively. CONCLUSIONS: Implementation of an ACS service resulted in a higher rate of index cholecystectomy and decreased emergency department visits and readmissions for biliary disease, and allowed for increased adherence to clinical practice guidelines for GSP. PMID- 26372636 TI - Resident and Fellow Participation in Breast Surgery: An American College of Surgeons NSQIP Clinical Outcomes Analysis. AB - BACKGROUND: In our present health and medical education system, participation of residents and fellows is under increasing scrutiny regarding their role in surgery and the outcomes of the procedure. Our goal was to perform a clinical outcomes analysis investigating resident and fellow participation in breast surgery. STUDY DESIGN: Early postoperative complication rates and total operation times for partial and simple mastectomy cases were gathered from the ACS-NSQIP database. The cases were divided based on the training level of the participating resident surgeon: junior (post-graduate year [PGY] 1 to 2), senior (PGY 3 to 5), fellow (PGY > 5), as well as an attending only group (no resident present). We compared the clinical outcomes of each group with the attending only group. Statistical analysis included odds ratios and regression analysis that analyzed the correlation between years in training vs complication rate, and years in training vs total operation time. RESULTS: A total of 13,254 cases were identified, and residents participated in 64% of them. There was no statistically significant difference in rate of complications between any of the trainee groups when compared with the attending only group. However, total operative times were correlated with training year levels and found to be significantly lower with each year of training (R(2) = 0.53, p = 0.025 for partial mastectomy; R(2) = 0.45, p = 0.046 for complete mastectomy). CONCLUSIONS: Resident/fellow participation does not negatively affect early postoperative breast surgery outcomes, and complication rates are unrelated to the training level of the participating resident/fellow surgeon. PMID- 26372637 TI - Successful Tumor Navigation Technique During Intrathoracoscopic Esophagectomy: Laparoscopic Ultrasonography Using Endoscopically Placed Marking Clips. PMID- 26372638 TI - 2013 ACC/AHA versus 2004 NECP ATP III Guidelines in the Assignment of Statin Treatment in a Korean Population with Subclinical Coronary Atherosclerosis. AB - BACKGROUND: The usefulness of the 2013 ACC/AHA guidelines for the management of blood cholesterol in the Asian population remains controversial. In this study, we investigated whether eligibility for statin therapy determined by the 2013 ACC/AHA guidelines is better aligned with the presence of subclinical coronary atherosclerosis detected by CCTA (coronary computed tomography angiography) compared to the previously recommended 2004 NCEP ATP III guidelines. METHODS: We collected the data from 5,837 asymptomatic subjects who underwent CCTA using MDCT during routine health examinations. Based on risk factor assessment and lipid data, we determined guideline-based eligibility for statin therapy according to the 2013 ACC/AHA and 2004 NCEP ATP III guidelines. We defined the presence and severity of subclinical coronary atherosclerosis detected in CCTA according to the presence of significant coronary artery stenosis (defined as >50% stenosis), plaques, and the degree of coronary calcification. RESULTS: As compared to the 2004 ATP III guidelines, a significantly higher proportion of subjects with significant coronary stenosis (61.8% vs. 33.8%), plaques (52.3% vs. 24.7%), and higher CACS (CACS >100, 63.6% vs. 26.5%) was assigned to statin therapy using the 2013 ACC/AHA guidelines (P < .001 for all variables). The area under the curves of the pooled cohort equation of the new guidelines in detecting significant stenosis, plaques, and higher CACS were significantly higher than those of the Framingham risk calculator. CONCLUSIONS: Compared to the previous ATP III guidelines, the 2013 ACC/AHA guidelines were more sensitive in identifying subjects with subclinical coronary atherosclerosis detected by CCTA in an Asian population. PMID- 26372639 TI - Cross-border reproductive care for law evasion: should physicians be allowed to help infertility patients evade the law of their own country? AB - There are fundamental differences between countries with regard to legislation on assisted reproduction. Many infertility patients are looking to evade the law of their own country and make use of reproductive services abroad. The role of the local physician in cross-border reproductive care for law evasion has been characterized as "channeling local patients to foreign medical establishments" and "against the spirit and essence of the law". The logical view is that by supporting CBRC for law evasion, physicians are essentially supporting immoral behavior. We will tackle this position on two levels. First, we will argue that governments should generally be tolerant toward people with different positions on assisted reproduction. Second, we will show that contributing to cross-border reproductive care for law evasion is not necessarily immoral, because the prima facie wrongness of complicity in law evasion can be outweighed by the fact that physicians should act in the best interest of the patient. Several countries have tried to prevent local physicians from helping patients to make use of reproductive services abroad, but they should rather leave it up to the individual physicians to decide whether or not to support a particular patient. PMID- 26372640 TI - Hypoxaemia as a Mortality Risk Factor in Acute Lower Respiratory Infections in Children in Low and Middle-Income Countries: Systematic Review and Meta-Analysis. AB - OBJECTIVE: To evaluate the association between hypoxaemia and mortality from acute lower respiratory infections (ALRI) in children in low- and middle-income countries (LMIC). DESIGN: Systematic review and meta-analysis. STUDY SELECTION: Observational studies reporting on the association between hypoxaemia and death from ALRI in children below five years in LMIC. DATA SOURCES: Medline, Embase, Global Health Library, Lilacs, and Web of Science to February 2015. RISK OF BIAS ASSESSMENT: Quality In Prognosis Studies tool with minor adaptations to assess the risk of bias; funnel plots and Egger's test to evaluate publication bias. RESULTS: Out of 11,627 papers retrieved, 18 studies from 13 countries on 20,224 children met the inclusion criteria. Twelve (66.6%) studies had either low or moderate risk of bias. Hypoxaemia defined as oxygen saturation rate (SpO2) <90% associated with significantly increased odds of death from ALRI (OR 5.47, 95% CI 3.93 to 7.63) in 12 studies on 13,936 children. An Sp02 <92% associated with a similar increased risk of mortality (OR 3.66, 95% CI 1.42 to 9.47) in 3 studies on 673 children. Sensitivity analyses (excluding studies with high risk of bias and using adjusted OR) and subgroup analyses (by: altitude, definition of ALRI, country income, HIV prevalence) did not affect results. Only one study was performed on children living at high altitude. CONCLUSIONS: The results of this review support the routine evaluation of SpO2 for identifying children with ALRI at increased risk of death. Both a Sp02 value of 92% and 90% equally identify children at increased risk of mortality. More research is needed on children living at high altitude. Policy makers in LMIC should aim at improving the regular use of pulse oximetry and the availability of oxygen in order to decrease mortality from ALRI. PMID- 26372642 TI - Ontogeny of Foraging Competence in Capuchin Monkeys (Cebus capucinus) for Easy versus Difficult to Acquire Fruits: A Test of the Needing to Learn Hypothesis. AB - Which factors select for long juvenile periods in some species is not well understood. One potential reason to delay the onset of reproduction is slow food acquisition rates, either due to competition (part of the ecological risk avoidance hypothesis), or due to a decreased foraging efficiency (a version of the needing to learn hypothesis). Capuchins provide a useful genus to test the needing to learn hypothesis because they are known for having long juvenile periods and a difficult-to-acquire diet. Generalized, linear, mixed models with data from 609 fruit forage focal follows on 49, habituated, wild Cebus capucinus were used to test two predictions from the needing-to-learn hypothesis as it applies to fruit foraging skills: 1) capuchin monkeys do not achieve adult foraging return rates for difficult-to-acquire fruits before late in the juvenile period; and 2) variance in return rates for these fruits is at least partially associated with differences in foraging skill. In support of the first prediction, adults, compared with all younger age classes, had significantly higher foraging return rates when foraging for fruits that were ranked as difficult-to-acquire (return rates relative to adults: 0.30-0.41, p-value range 0.008-0.016), indicating that the individuals in the group who have the most foraging experience also achieve the highest return rates. In contrast, and in support of the second prediction, there were no significant differences between age classes for fruits that were ranked as easy to acquire (return rates relative to adults: 0.97-1.42, p-value range 0.086-0.896), indicating that strength and/or skill are likely to affect return rates. In addition, fruits that were difficult to acquire were foraged at nearly identical rates by adult males and significantly smaller (and presumably weaker) adult females (males relative to females: 1.01, p = 0.978), while subadult females had much lower foraging efficiency than the similarly-sized but more experienced adult females (subadults relative to adults: 0.34, p = 0.052), indicating that skill, specifically, is likely to have an effect on return rates. These results are consistent with the needing to learn hypothesis and indicate that long juvenile periods in capuchins may be the result of selection for more time to learn foraging skills for difficult-to-acquire fruits. PMID- 26372641 TI - In Situ Transplantation of Alginate Bioencapsulated Adipose Tissues Derived Stem Cells (ADSCs) via Hepatic Injection in a Mouse Model. AB - OBJECTIVE: Adipose tissue derived stem cells (ADSCs) transplantation has recently gained widespread enthusiasm, particularly in the perspective to use them as potential alternative cell sources for hepatocytes in cell based therapy, mainly because of their capability of hepatogenic differentiation in vitro and in vivo. But some challenges remain to be addressed, including whether ADSCs can be provided effectively to the target organ and whether subsequent proliferation of transplanted cells can be achieved. To date, intrasplenic injection is the conventional method to deliver ADSCs into the liver; however, a number of donor cells retained in the spleen has been reported. In this study, our objective is to evaluate a novel route to transplant ADSCs specifically to the liver. We aimed to test the feasibility of in situ transplantation of ADSCs by injecting bioencapsulated ADSCs into the liver in mouse model. METHODS: The ADSCs isolated from human alpha 1 antitrypsin (M-hAAT) transgenic mice were used to allow delivered ADSCs be readily identified in the liver of recipient mice, and alginate was selected as a cell carrier. We first evaluated whether alginate microspheres are implantable into the liver tissue by injection and whether ADSCs could migrate from alginate microspheres (study one). Once proven, we then examined the in vivo fate of ADSCs loaded microspheres in the liver. Specifically, we evaluated whether transplanted, undifferentiated ASDCs could be induced by the local microenvironment toward hepatogenic differentiation and the distribution of surviving ADSCs in major tissue organs (study two). RESULTS: Our results indicated ADSCs loaded alginate microspheres were implantable into the liver. Both degraded and residual alginate microspheres were observed in the liver up to three weeks. The viable ADSCs were detectable surrounding degraded and residual alginate microspheres in the liver and other major organs such as bone marrow and the lungs. Importantly, transplanted ADSCs underwent hepatogenic differentiation to become cells expressing albumin in the liver. These findings improve our understanding of the interplay between ADSCs (donor cells), alginate (biomaterial), and local microenvironment in a hepatectomized mouse model, and might improve the strategy of in situ transplantation of ADSCs in treating liver diseases. PMID- 26372643 TI - The Interplay between Scientific Overlap and Cooperation and the Resulting Gain in Co-Authorship Interactions. AB - Considering the importance of scientific interactions, understanding the principles that govern fruitful scientific research is crucial to policy makers and scientists alike. The outcome of an interaction is to a large extent dependent on the balancing of contradicting motivations accompanying the establishment of collaborations. Here, we assembled a dataset of nearly 20,000 publications authored by researchers affiliated with ten top universities. Based on this data collection, we estimated the extent of different interaction types between pairwise combinations of researchers. We explored the interplay between the overlap in scientific interests and the tendency to collaborate, and associated these estimates with measures of scientific quality and social accessibility aiming at studying the typical resulting gain of different interaction patterns. Our results show that scientists tend to collaborate more often with colleagues with whom they share moderate to high levels of mutual interests and knowledge while cooperative tendency declines at higher levels of research-interest overlap, suggesting fierce competition, and at the lower levels, suggesting communication gaps. Whereas the relative number of alliances dramatically differs across a gradient of research overlap, the scientific impact of the resulting articles remains similar. When considering social accessibility, we find that though collaborations between remote researchers are relatively rare, their quality is significantly higher than studies produced by close-circle scientists. Since current collaboration patterns do not necessarily overlap with gaining optimal scientific quality, these findings should encourage scientists to reconsider current collaboration strategies. PMID- 26372646 TI - A Batteryless Sensor ASIC for Implantable Bio-Impedance Applications. AB - The measurement of the biological tissue's electrical impedance is an active research field that has attracted a lot of attention during the last decades. Bio impedances are closely related to a large variety of physiological conditions; therefore, they are useful for diagnosis and monitoring in many medical applications. Measuring living tissues, however, is a challenging task that poses countless technical and practical problems, in particular if the tissues need to be measured under the skin. This paper presents a bio-impedance sensor ASIC targeting a battery-free, miniature size, implantable device, which performs accurate 4-point complex impedance extraction in the frequency range from 2 kHz to 2 MHz. The ASIC is fabricated in 150 nm CMOS, has a size of 1.22 mm * 1.22 mm and consumes 165 MUA from a 1.8 V power supply. The ASIC is embedded in a prototype which communicates with, and is powered by an external reader device through inductive coupling. The prototype is validated by measuring the impedances of different combinations of discrete components, measuring the electrochemical impedance of physiological solution, and performing ex vivo measurements on animal organs. The proposed ASIC is able to extract complex impedances with around 1 Omega resolution; therefore enabling accurate wireless tissue measurements. PMID- 26372644 TI - The Role of Sirt1 in Bile Acid Regulation during Calorie Restriction in Mice. AB - Sirtuin 1 (Sirt1) is an NAD+-dependent protein deacetylase that is proposed to mediate many health-promoting effects of calorie restriction (CR). We recently reported that short-term CR increased the bile acid (BA) pool size in mice, likely due to increased BA synthesis in liver. Given the important role of Sirt1 in the regulation of glucose, lipid, as well as BA metabolism, we hypothesized that the CR-induced increase in BAs is Sirt1-dependent. To address this, the present study utilized genetically-modified mice that were Sirt1 loss of function (liver knockout, LKO) or Sirt1 gain of function (whole body-transgenic, TG). Three genotypes of mice (Sirt1-LKO, wild-type, and Sirt1-TG) were each randomly divided into ad libitum or 40% CR feeding for one month. BAs were extracted from various compartments of the enterohepatic circulation, followed by BA profiling by UPLC-MS/MS. CR increased the BA pool size and total BAs in serum, gallbladder, and small intestine. The CR-induced increase in BA pool size correlated with the tendency of increase in the expression of the rate-limiting BA-synthetic enzyme Cyp7a1. However, in contrast to the hypothesis, the CR-induced increase in BA pool size and Cyp7a1 expression was still observed with ablated expression of Sirt1 in liver, and completely suppressed with whole-body overexpression of Sirt1. Furthermore, in terms of BA composition, CR increased the ratio of 12alpha hydroxylated BAs regardless of Sirt1 genotypes. In conclusion, the CR-induced alterations in BA pool size, BA profiles, and expression of BA-related genes do not appear to be dependent on Sirt1. PMID- 26372647 TI - Controlling E. coli Gene Expression Noise. AB - Intracellular protein copy numbers show significant cell-to-cell variability within an isogenic population due to the random nature of biological reactions. Here we show how the variability in copy number can be controlled by perturbing gene expression. Depending on the genetic network and host, different perturbations can be applied to control variability. To understand more fully how noise propagates and behaves in biochemical networks we developed stochastic control analysis (SCA) which is a sensitivity-based analysis framework for the study of noise control. Here we apply SCA to synthetic gene expression systems encoded on plasmids that are transformed into Escherichia coli. We show that (1) dual control of transcription and translation efficiencies provides the most efficient way of noise-versus-mean control. (2) The expressed proteins follow the gamma distribution function as found in chromosomal proteins. (3) One of the major sources of noise, leading to the cell-to-cell variability in protein copy numbers, is related to bursty translation. (4) By taking into account stochastic fluctuations in autofluorescence, the correct scaling relationship between the noise and mean levels of the protein copy numbers was recovered for the case of weak fluorescence signals. PMID- 26372645 TI - ADAP2 Is an Interferon Stimulated Gene That Restricts RNA Virus Entry. AB - Interferon stimulated genes (ISGs) target viruses at various stages of their infectious life cycles, including at the earliest stage of viral entry. Here we identify ArfGAP with dual pleckstrin homology (PH) domains 2 (ADAP2) as a gene upregulated by type I IFN treatment in a STAT1-dependent manner. ADAP2 functions as a GTPase-activating protein (GAP) for Arf6 and binds to phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) and PI(3,4)P2. We show that overexpression of ADAP2 suppresses dengue virus (DENV) and vesicular stomatitis virus (VSV) infection in an Arf6 GAP activity-dependent manner, while exerting no effect on coxsackievirus B (CVB) or Sendai virus (SeV) replication. We further show that ADAP2 expression induces macropinocytosis and that ADAP2 strongly associates with actin-enriched membrane ruffles and with Rab8a- and LAMP1-, but not EEA1- or Rab7 , positive vesicles. Utilizing two techniques--light-sensitive neutral red (NR) containing DENV and fluorescence assays for virus internalization--we show that ADAP2 primarily restricts DENV infection at the stage of virion entry and/or intracellular trafficking and that incoming DENV and VSV particles associate with ADAP2 during their entry. Taken together, this study identifies ADAP2 as an ISG that exerts antiviral effects against RNA viruses by altering Arf6-mediated trafficking to disrupt viral entry. PMID- 26372648 TI - Synthetic Biology: A Unifying View and Review Using Analog Circuits. AB - We review the field of synthetic biology from an analog circuits and analog computation perspective, focusing on circuits that have been built in living cells. This perspective is well suited to pictorially, symbolically, and quantitatively representing the nonlinear, dynamic, and stochastic (noisy) ordinary and partial differential equations that rigorously describe the molecular circuits of synthetic biology. This perspective enables us to construct a canonical analog circuit schematic that helps unify and review the operation of many fundamental circuits that have been built in synthetic biology at the DNA, RNA, protein, and small-molecule levels over nearly two decades. We review 17 circuits in the literature as particular examples of feedforward and feedback analog circuits that arise from special topological cases of the canonical analog circuit schematic. Digital circuit operation of these circuits represents a special case of saturated analog circuit behavior and is automatically incorporated as well. Many issues that have prevented synthetic biology from scaling are naturally represented in analog circuit schematics. Furthermore, the deep similarity between the Boltzmann thermodynamic equations that describe noisy electronic current flow in subthreshold transistors and noisy molecular flux in biochemical reactions has helped map analog circuit motifs in electronics to analog circuit motifs in cells and vice versa via a 'cytomorphic' approach. Thus, a body of knowledge in analog electronic circuit design, analysis, simulation, and implementation may also be useful in the robust and efficient design of molecular circuits in synthetic biology, helping it to scale to more complex circuits in the future. PMID- 26372649 TI - Efficient Sampling of Bacterial Signal Transduction for Detection of Pulse Amplitude Modulated Molecular Signals. AB - The sampling of the bacterial signal transduction is investigated for molecular communication (MC). It is assumed that the finite-duration amplitude modulated, i.e., pulse-amplitude modulated (PAM), concentration of a certain type of molecule is used for information transmission. The bacterial signaling pathway is modified to transduce the input molecules to the output signal, i.e., produce green fluorescent protein (GFP). The bacterial signal transduction is composed of a set of biochemical reactions which impose randomness on the response. Therefore, the input-output relation, the timing issues, and the noise effects for the bacteria response are characterized based on both analytical and experimental observations. Sampling schemes for the raw bacteria response are proposed based on the total response duration, the peak value, the ramp-up slope, and the ramp-down slope. Each sampling scheme is shown to be providing a one-to one and monotonic function of the input. The sampling based on the ramp-up slope is shown to be statistically favorable for the detection of PAM molecular signals. Accordingly, the time interval selection and non-coherent sampling are studied for the efficient calculation of the ramp-up slope from the raw bacteria response. This work provides a basis for the sampling of the raw bacteria response and enables accurate detection of PAM molecular signals via bacterial response for MC and sensing applications. PMID- 26372650 TI - Design, synthesis and biological evaluation of novel pyrazolo-pyrimidinones as DPP-IV inhibitors in diabetes. AB - We report the design, synthesis, biological activity and docking studies of series of novel pyrazolo[3,4-d]pyrimidinones as DPP-IV inhibitors in diabetes. Molecules were synthesized and evaluated for their DPP-IV inhibition activity. Compounds 5e, 5k, 5o and 6a were found to be potent inhibitors of DPP-IV enzyme. Amongst all the synthesized compounds, 6-methyl-5-(4-methylpyridin-2-yl)-1-phenyl 1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one (5k) was found to be the most active based on in vitro DPP-IV studies and also exhibited promising in vivo blood glucose lowering activity in male Wistar rats. PMID- 26372651 TI - Phenothiazine-based CaaX competitive inhibitors of human farnesyltransferase bearing a cysteine, methionine, serine or valine moiety as a new family of antitumoral compounds. AB - A new family of CaaX competitive inhibitors of human farnesyltransferase based on phenothiazine and carbazole skeleton bearing a l-cysteine, l-methionine, l-serine or l-valine moiety was designed, synthesized and biologically evaluated. Phenothiazine derivatives proved to be more active than carbazole-based compounds. Phenothiazine 1b with cysteine residue was the most promising inhibitor of human farnesyltransferase in the current study. PMID- 26372652 TI - Pentafluorosulfanyl-containing flufenamic acid analogs: Syntheses, properties and biological activities. AB - Pentafluorosulfanyl-containing analogs of flufenamic acid have been synthesized in high yields. Computationally, pKa, LogP and LogD values have been determined. Initial bioactivity studies reveal effects as ion channel modulators and inhibitory activities on aldo-keto reductase 1C3 (AKR1C3) as well as COX-1 and COX-2. PMID- 26372653 TI - Structure activity optimization of 6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3 a]pyrazines as Jak1 kinase inhibitors. AB - Previous work investigating tricyclic pyrrolopyrazines as kinase cores led to the discovery that 1-cyclohexyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazine (12) had Jak inhibitory activity. Herein we describe our initial efforts to develop orally bioavailable analogs of 12 with improved selectivity of Jak1 over Jak2. PMID- 26372654 TI - Synthesis and structure-activity studies of the V-ATPase inhibitor saliphenylhalamide (SaliPhe) and simplified analogs. AB - An efficient total synthesis of the potent V-ATPase inhibitor saliphenylhalamide (SaliPhe), a synthetic variant of the natural product salicylihalamide A (SaliA), has been accomplished aimed at facilitating the development of SaliPhe as an anticancer and antiviral agent. This new approach enabled facile access to derivatives for structure-activity relationship studies, leading to simplified analogs that maintain SaliPhe's biological properties. These studies will provide a solid foundation for the continued evaluation of SaliPhe and analogs as potential anticancer and antiviral agents. PMID- 26372656 TI - Method for Providing Electrovibration with Uniform Intensity. AB - Electrovibration is a type of surface haptics that can modulate lateral forces acting between a fingertip and a touch surface. Electrovibration is fast, consumes little power, and does not involve the use of any mechanical actuators. However, it suffers from problems such as nonuniform perceived intensity due to varying environmental impedances, as well as possible electric shock, which have to be solved for commercialization. In this paper, a current feedback method is proposed to provide uniform intensity of electrovibration, regardless of the varying environmental impedances. The proposed method can also prevent electric shock. To show the effectiveness of the proposed method, a hardware prototype was developed and a user study was conducted. The user study result shows that the proposed current control method can provide significantly more uniform perceived intensity of electrovibration as compared with the conventional voltage control method. PMID- 26372655 TI - Environmental Quality Assessment of Bizerte Lagoon (Tunisia) Using Living Foraminifera Assemblages and a Multiproxy Approach. AB - This study investigated the environmental quality of the Bizerte Lagoon (Tunisia) through an integrated approach that combined environmental, biogeochemical, and living benthic foraminiferal analyses. Specifically, we analyzed the physicochemical parameters of the water and sediment. The textural, mineralogical, and geochemical characteristics of the sediment, including total organic carbon, total nitrogen, simultaneously extracted metals (SEM), acid volatile sulfides (AVS), chlorophyll a, CaCO3, and changes in bacterial populations and carbon isotopes were measured. The SEM/AVS values indicated the presence of relatively high concentrations of toxic metals in only some areas. Foraminiferal assemblages were dominated by species such as A. parkinsoniana (20 91%), Bolivina striatula (<40%), Hopkinsina atlantica (<17%), and Bolivina ordinaria (<15%) that cannot be considered typical of impacted coastal lagoons both in Mediterranean and northeast Atlantic regions. The results of this work suggest that Bizerte Lagoon is a unique setting. This lagoon is populated by typical marine species that invaded this ecosystem, attracted not only by the prevailing favorable environmental conditions but also by the abundance and quality of food. The results indicate that the metal pollution found in some areas have a negative impact on the assemblages of foraminifera. At present, however, this negative impact is not highly alarming. PMID- 26372657 TI - Sharp Tactile Line Presentation Using Edge Stimulation Method. AB - We provide supplemental data to a vibrator array tactile display, as well as additional data for application of the edge stimulation (ES) method proposed in our previous study. By vibrating two surfaces in different phases and touching their boundary, a strong continuous line sensation, not on the vibrators themselves, but along the boundary, is obtained. This vibrotactile edge is suitable for presenting virtual lines, areas, and shapes on a rigid flat surface. We investigated the fundamental performance of the ES method through psychophysical experiments. The effects on the vibrotactile detection thresholds were investigated for three mechanical parameters, i.e., the vibratory frequency, the phase difference between the vibrations, and the gap distance between adjoining vibratory surfaces. Two-line discrimination thresholds for lines presented by the ES method were also determined. We found that the detection thresholds under the ES method was lower than 10 um even at the low frequencies (lower than 50 Hz), which is significantly lower than that under simply touching to a single vibratory surface. A comparison of the perceived widths revealed that the ES method provides a more localized tactile image than a single-pin vibrator or a flat-top vibrator. A 3 X 3 vibrator array display was developed using the ES method based on the properties obtained from the experiments. Seven categories of display patterns were presented with the ES array display and the participants' responses matched at 95 percent. PMID- 26372658 TI - Neuromorphic Artificial Touch for Categorization of Naturalistic Textures. AB - We implemented neuromorphic artificial touch and emulated the firing behavior of mechanoreceptors by injecting the raw outputs of a biomimetic tactile sensor into an Izhikevich neuronal model. Naturalistic textures were evaluated with a passive touch protocol. The resulting neuromorphic spike trains were able to classify ten naturalistic textures ranging from textiles to glass to BioSkin, with accuracy as high as 97%. Remarkably, rather than on firing rate features calculated over the stimulation window, the highest achieved decoding performance was based on the precise spike timing of the neuromorphic output as captured by Victor Purpura distance. We also systematically varied the sliding velocity and the contact force to investigate the role of sensing conditions in categorizing the stimuli via the artificial sensory system. We found that the decoding performance based on the timing of neuromorphic spike events was robust for a broad range of sensing conditions. Being able to categorize naturalistic textures in different sensing conditions, these neurorobotic results pave the way to the use of neuromorphic tactile sensors in future real-life neuroprosthetic applications. PMID- 26372659 TI - An NFC-Enabled CMOS IC for a Wireless Fully Implantable Glucose Sensor. AB - This paper presents an integrated circuit (IC) that merges integrated optical and temperature transducers, optical interface circuitry, and a near-field communication (NFC)-enabled digital, wireless readout for a fully passive implantable sensor platform to measure glucose in people with diabetes. A flip chip mounted LED and monolithically integrated photodiodes serve as the transduction front-end to enable fluorescence readout. A wide-range programmable transimpedance amplifier adapts the sensor signals to the input of an 11-bit analog-to-digital converter digitizing the measurements. Measurement readout is enabled by means of wireless backscatter modulation to a remote NFC reader. The system is able to resolve current levels of less than 10 pA with a single fluorescent measurement energy consumption of less than 1 MUJ. The wireless IC is fabricated in a 0.6-MUm-CMOS process and utilizes a 13.56-MHz-based ISO15693 for passive wireless readout through a NFC interface. The IC is utilized as the core interface to a fluorescent, glucose transducer to enable a fully implantable sensor-based continuous glucose monitoring system. PMID- 26372660 TI - Three-Dimensional Needle Shape Estimation in TRUS-Guided Prostate Brachytherapy Using 2-D Ultrasound Images. AB - In this paper, we propose an automated method to reconstruct the three dimensional (3-D) needle shape during needle insertion procedures using only 2-D transverse ultrasound (US) images. Using a set of transverse US images, image processing and random sample consensus are used to locate the needle within each image and estimate the needle shape. The method is validated with an in vitro needle insertion setup and a transparent tissue phantom, where two orthogonal cameras are used to capture the true 3-D needle shape for verification. Results showed that the use of at least three images obtained at 75% of the maximum insertion depth or greater allows for maximum needle shape estimation errors of less than 2 mm. In addition, the needle shape can be calculated consistently as long as the needle can be identified in 30% of the transverse US images obtained. Application to permanent prostate brachytherapy is also presented, where the estimated needle shape is compared to manual segmentation and sagittal US images. Our method is intended to help to assess needle placement during manual or robot assisted needle insertion procedures after the needle has been inserted. PMID- 26372661 TI - Improved Patch-Based Automated Liver Lesion Classification by Separate Analysis of the Interior and Boundary Regions. AB - The bag-of-visual-words (BoVW) method with construction of a single dictionary of visual words has been used previously for a variety of classification tasks in medical imaging, including the diagnosis of liver lesions. In this paper, we describe a novel method for automated diagnosis of liver lesions in portal-phase computed tomography (CT) images that improves over single-dictionary BoVW methods by using an image patch representation of the interior and boundary regions of the lesions. Our approach captures characteristics of the lesion margin and of the lesion interior by creating two separate dictionaries for the margin and the interior regions of lesions ("dual dictionaries" of visual words). Based on these dictionaries, visual word histograms are generated for each region of interest within the lesion and its margin. For validation of our approach, we used two datasets from two different institutions, containing CT images of 194 liver lesions (61 cysts, 80 metastasis, and 53 hemangiomas). The final diagnosis of each lesion was established by radiologists. The classification accuracy for the images from the two institutions was 99% and 88%, respectively, and 93% for a combined dataset. Our new BoVW approach that uses dual dictionaries shows promising results. We believe the benefits of our approach may generalize to other application domains within radiology. PMID- 26372662 TI - Novel Fuzzy Modeling and Synchronization of Chaotic Systems With Multinonlinear Terms by Advanced Ge-Li Fuzzy Model. AB - Ge and Li proposed an alternative strategy to model and synchronize two totally different nonlinear systems in the end of 2011, which provided a new version for fuzzy modeling and has been applied to several fields to simplify their modeling works and solve the mismatch problems [1]-[17]. However, the proposed model limits the number of nonlinear terms in each equation so that this model could not be used in all kinds of nonlinear dynamic systems. As a result, in this paper, a more efficient and comprehensive advanced-Ge-Li fuzzy model is given to further release the limitation and improve the effectiveness of the original one. The novel fuzzy model can be applied to all kinds of complex nonlinear systems- this is the universal strategy and only m x 2 fuzzy rules as well as two linear subsystems are needed to simulate nonlinear behaviors (m is the number of states in a nonlinear dynamic system), whatever the nonlinear terms are copious or complicated. Further, the fuzzy synchronization of two nonlinear dynamic systems with totally distinct structures can be achieved via only two sets of control gains designed through the novel fuzzy model as well as its corresponding fuzzy synchronization scheme. Two complicated dynamic systems are designed to be the illustrations, Mathieu-Van der pol system with uncertainties and Quantum-cellular neural networks nano system with uncertainties, to show the effectiveness and feasibility of the novel fuzzy model. PMID- 26372663 TI - TNFalpha and IL-6 Responses to Particulate Matter in Vitro: Variation According to PM Size, Season, and Polycyclic Aromatic Hydrocarbon and Soil Content. AB - BACKGROUND: Observed seasonal differences in particulate matter (PM) associations with human health may be due to their composition and to toxicity-related seasonal interactions. OBJECTIVES: We assessed seasonality in PM composition and in vitro PM pro-inflammatory potential using multiple PM samples. METHODS: We collected 90 weekly PM10 and PM2.5 samples during the rainy-warm and dry-cold seasons in five urban areas with different pollution sources. The elements, polycyclic aromatic hydrocarbons (PAHs), and endotoxins identified in the samples were subjected to principal component analysis (PCA). We tested the potential of the PM to induce tumor necrosis factor alpha (TNFalpha) and interleukin 6 (IL-6) secretion in cultured human monocytes (THP-1), and we modeled pro-inflammatory responses using the component scores. RESULTS: PM composition varied by size and by season. PCA identified two main components that varied by season. Combustion related constituents (e.g., vanadium, benzo[a]pyrene, benzo[a]anthracene) mainly comprised component 1 (C1). Soil-related constituents (e.g., endotoxins, silicon, aluminum) mainly comprised component 2 (C2). PM from the rainy-warm season was high in C2. PM (particularly PM2.5) from the dry-cold season was rich in C1. Elevated levels of cytokine production were associated with PM10 and C2 (rainy warm season), whereas reduced levels of cytokine production were associated with PM2.5 and C1 (dry-cold season). TNFalpha secretion was increased following exposure to PM with high (vs. low) C2 content, but TNFalpha secretion in response to PM was decreased following exposure to samples containing >= 0.1% of C1 related PAHs, regardless of C2 content. The results of the IL-6 assays suggested more complex interactions between PM components and particle size. CONCLUSIONS: Variations in PM soil and PAH content underlie seasonal and PM size-related patterns in TNFalpha secretion. These results suggest that the mixture of components in PM explains some seasonal differences in associations between health outcomes and PM in epidemiologic studies. CITATION: Manzano-Leon N, Serrano-Lomelin J, Sanchez BN, Quintana-Belmares R, Vega E, Vazquez-Lopez I, Rojas-Bracho L, Lopez-Villegas MT, Vadillo-Ortega F, De Vizcaya-Ruiz A, Rosas Perez I, O'Neill MS, Osornio-Vargas AR. 2016. TNFalpha and IL-6 responses to particulate matter in vitro: variation according to PM size, season, and polycyclic aromatic hydrocarbon and soil content. Environ Health Perspect 124:406 412; http://dx.doi.org/10.1289/ehp.1409287. PMID- 26372664 TI - Radon Exposure, IL-6 Promoter Variants, and Lung Squamous Cell Carcinoma in Former Uranium Miners. AB - BACKGROUND: High radon exposure is a risk factor for squamous cell carcinoma, a major lung cancer histology observed in former uranium miners. Radon exposure can cause oxidative stress, leading to pulmonary inflammation. Interleukin-6 (IL-6) is a pro-carcinogenic inflammatory cytokine that plays a pivotal role in lung cancer development. OBJECTIVES: We assessed whether single nucleotide polymorphisms (SNPs) in the IL6 promoter are associated with lung cancer in former uranium miners with high occupational exposure to radon gas. METHODS: Genetic associations were assessed in a case-control study of former uranium miners (242 cases and 336 controls). A replication study was performed using data from the Gene Environment Association Studies (GENEVA) Genome Wide Association Study (GWAS) of Lung Cancer and Smoking. Functional relevance of the SNPs was characterized using in vitro approaches. RESULTS: We found that rs1800797 was associated with squamous cell carcinoma in miners and with a shorter time between the midpoint of the period of substantial exposure and diagnosis among the cases. Furthermore, rs1800797 was also associated with lung cancer among never smokers in the GENEVA dataset. Functional studies identified that the risk allele was associated with increased basal IL-6 mRNA level and greater promoter activity. Furthermore, fibroblasts with the risk allele showed greater induction of IL-6 secretion by hydrogen peroxide or benzo[a]pyrene diolepoxide treatments. CONCLUSIONS: An IL6 promoter variant was associated with lung cancer in uranium miners and never smokers in two external study populations. The associations are strongly supported by the functional relevance that the IL6 promoter SNP affects basal expression and carcinogen-induced IL-6 secretion. CITATION: Leng S, Thomas CL, Snider AM, Picchi MA, Chen W, Willis DG, Carr TG, Krzeminski J, Desai D, Shantu A, Lin Y, Jacobson MR, Belinsky SA. 2016. Radon exposure, IL-6 promoter variants, and lung squamous cell carcinoma in former uranium miners. Environ Health Perspect 124:445-451; http://dx.doi.org/10.1289/ehp.1409437. PMID- 26372665 TI - Variability of Metal Levels in Spot, First Morning, and 24-Hour Urine Samples over a 3-Month Period in Healthy Adult Chinese Men. AB - BACKGROUND: Metals in single spot urine samples are often used to estimate individual exposure in human studies. However, measurements in urine could vary greatly over time due to variable exposure, potentially leading to exposure misclassification. OBJECTIVE: We examined the variability of metal levels in the urine of 11 men who provided 529 samples on 8 days during a 3-month period, which corresponds to the duration of spermatogenesis. METHOD: The urinary levels of arsenic (As), cadmium (Cd), cobalt (Co), copper (Cu), lead (Pb), molybdenum (Mo), and nickel (Ni) were measured using inductively coupled plasma-mass spectrometry. We calculated the intraclass correlation coefficients (ICCs) to assess the reproducibility of metal measures and computed the sensitivity and specificity to evaluate how well spot urine samples determined the individuals' 3-month average exposure. RESULTS: Fair to good reproducibility was observed for the serial measurements of Cd (ICC = 0.53) in spot samples collected during the 3-month period, whereas the serial measurements of As, Co, Cu, Pb, Mo, and Ni showed poor reproducibility (ICCs = 0.01-0.29). Use of single spot urine samples to classify the high (top 33%) 3-month average metal levels had uniformly high specificities (0.70-0.84) but relatively low sensitivities (0.40-0.57), except for Cd (0.77). The minimum number of specimens (k) required to estimate the participant-specific mean for the seven metals within 20% of the "true" values ranged from 3 for Cd to 27 for Ni. CONCLUSIONS: The high variability observed in the urinary levels of As, Co, Cu, Pb, Mo, and Ni suggests that a single measurement provides only a brief snapshot in time of the exposure levels of an individual, which can result in a moderate degree of exposure misclassification. CITATION: Wang YX, Feng W, Zeng Q, Sun Y, Wang P, You L, Yang P, Huang Z, Yu SL, Lu WQ. 2016. Variability of metal levels in spot, first morning, and 24-hour urine samples over a 3-month period in healthy adult Chinese men. Environ Health Perspect 124:468-476; http://dx.doi.org/10.1289/ehp.1409551. PMID- 26372666 TI - Cross-Talk in the Female Rat Mammary Gland: Influence of Aryl Hydrocarbon Receptor on Estrogen Receptor Signaling. AB - BACKGROUND: Cross-talk between the aryl hydrocarbon receptor (AHR) and the estrogen receptor (ER) plays a major role in signaling processes in female reproductive organs. OBJECTIVES: We investigated the influence of the AHR ligand 3-methylcholanthrene (3-MC) on ER-mediated signaling in mammary gland tissue of ovariectomized (ovx) rats. METHODS: After 14 days of hormonal decline, ovx rats were treated for 3 days with 4 MUg/kg 17beta-estradiol (E2), 15 mg/kg 8 prenylnaringenin (8-PN), 15 mg/kg 3-MC, or a combination of these compounds (E2 + 3-MC, 8-PN + 3-MC). Whole-mount preparations of the mammary gland were used to count terminal end buds (TEBs). Protein expression studies (immunohistochemistry, immunofluorescence), a cDNA microarray, pathway analyses, and quantitative real time polymerase chain reaction (qPCR) were performed to evaluate the interaction between AHR- and ER-mediated signaling pathways. RESULTS: E2 treatment increased the number of TEBs and the levels of Ki-67 protein and progesterone receptor (PR); this treatment also changed the expression of 325 genes by more than 1.5 fold. Although 3-MC treatment alone had marginal impact on gene or protein expression, when rats were co-treated with 3-MC and E2, 3-MC strongly inhibited E2-induced TEB development, protein synthesis, and the expression of nearly half of E2-induced genes. This inhibitory effect of 3-MC was partially mirrored when 8 PN was used as an ER ligand. The anti-estrogenicity of ligand-activated AHR was at least partly due to decreased protein levels of ERalpha in ductal epithelial cells. CONCLUSION: Our data show transcriptome-wide anti-estrogenic properties of ligand-activated AHR on ER-mediated processes in the mammary gland, thereby contributing an explanation for the chemopreventive and endocrine-disrupting potential of AHR ligands. CITATION: Helle J, Bader MI, Keiler AM, Zierau O, Vollmer G, Chittur SV, Tenniswood M, Kretzschmar G. 2016. Cross-talk in the female rat mammary gland: influence of aryl hydrocarbon receptor on estrogen receptor signaling. Environ Health Perspect 124:601-610; http://dx.doi.org/10.1289/ehp.1509680. PMID- 26372667 TI - Urinary Dialkyl Phosphate Concentrations and Lung Function Parameters in Adolescents and Adults: Results from the Canadian Health Measures Survey. AB - BACKGROUND: Epidemiological studies have reported associations between lung function parameters and organophosphate (OP) pesticide exposures in agricultural occupations, but to our knowledge associations have not been evaluated in general populations. OBJECTIVES: We examined associations between OP metabolite dialkyl phosphates (DAPs) and lung function using data from the Canadian Health Measures Survey (CHMS) Cycle 1. METHODS: Forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1), FEV1/FVC ratio, and forced expiratory flow between 25% and 75% of FVC (FEF25%-75%) were measured for 4,446 CHMS participants. Urinary concentrations of six DAP metabolites (DMP, DMTP, DMDTP, DEP, DETP, and DEDTP), smoking status, and other predictors of lung function were also measured in the CHMS-Cycle 1. Multiple linear regression analyses were used to examine the relationship between total DAP concentrations (SigmaDAPs) and lung function in adolescents (12-19 years) and adults (20-79 years). RESULTS: In adults, estimates from multiple regression analyses suggested that a 1-unit increase on natural logarithmic scale (171% increase on the original scale) in the creatinine corrected urinary concentration (nanomoles per gram creatinine) of SigmaDAP was associated with a 32.6-mL (95% CI: -57.2, -8.1) reduction in FVC, 32.6-mL (95% CI: -59.0, -6.3) reduction in FEV1, 0.2% (95% CI: -0.6, 0.2) reduction in FEV1/FVC ratio, and 53.1-mL/sec (95% CI: -113.9, 7.7) reduction in FEF25%-75%. In adolescents, associations between SigmaDAP and FEV1 were closer to the null and positive for FVC, whereas associations with FEV1/FVC and FEF25%-75% were negative, as in adults. However, none of the associations were significant in adolescents. CONCLUSIONS: The negative association between SigmaDAP and lung function in adult participants suggests a detrimental effect of OP pesticides on lung function in the adult general population. Further studies using prospective designs are warranted to confirm the findings reported in this study. CITATION: Ye M, Beach J, Martin JW, Senthilselvan A. 2016. Urinary dialkyl phosphate concentrations and lung function parameters in adolescents and adults: results from the Canadian Health Measures Survey. Environ Health Perspect 124:491-497; http://dx.doi.org/10.1289/ehp.1509745. PMID- 26372668 TI - Exposure Classification and Temporal Variability in Urinary Bisphenol A Concentrations among Couples in Utah--The HOPE Study. AB - BACKGROUND: Bisphenol A (BPA) is an endocrine disruptor and potential reproductive toxicant, but results of epidemiologic studies have been mixed and have been criticized for inadequate exposure assessment that often relies on a single measurement. OBJECTIVE: Our goal was to describe the distribution of BPA concentrations in serial urinary specimens, assess temporal variability, and provide estimates of exposure classification when randomly selected samples are used to predict average exposure. METHODS: We collected and analyzed 2,614 urine specimens from 83 Utah couples beginning in 2012. Female participants collected daily first-morning urine specimens during one to two menstrual cycles and male partners collected specimens during the woman's fertile window for each cycle. We measured urinary BPA concentrations and calculated geometric means (GM) for each cycle, characterized the distribution of observed values and temporal variability using intraclass correlation coefficients, and performed surrogate category analyses to determine how well repeat samples could classify exposure. RESULTS: The GM urine BPA concentration was 2.78 ng/mL among males and 2.44 ng/mL among females. BPA had a high degree of variability among both males (ICC = 0.18; 95% CI: 0.11, 0.26) and females (ICC = 0.11; 95% CI: 0.08, 0.16). Based on our more stringent surrogate category analysis, to reach proportions >= 0.80 for sensitivity, specificity, and positive predictive value (PPV) among females, 6 and 10 repeat samples for the high and low tertiles, respectively, were required. For the medium tertile, specificity reached 0.87 with 10 repeat samples, but even with 11 samples, sensitivity and PPV did not exceed 0.36. Five repeat samples, among males, yielded sensitivity and PPV values >= 0.75 for the high and low tertiles, but, similar to females, classification for the medium tertile was less accurate. CONCLUSION: Repeated urinary specimens are required to characterize typical BPA exposure. CITATION: Cox KJ, Porucznik CA, Anderson DJ, Brozek EM, Szczotka KM, Bailey NM, Wilkins DG, Stanford JB. 2016. Exposure classification and temporal variability in urinary bisphenol A concentrations among couples in Utah-the HOPE study. Environ Health Perspect 124:498-506; http://dx.doi.org/10.1289/ehp.1509752. PMID- 26372669 TI - Polybrominated Diphenyl Ether Exposure and Thyroid Function Tests in North American Adults. AB - BACKGROUND: Polybrominated diphenyl ethers (PBDEs) are flame-retardant chemicals that are added to many consumer products. Multiple animal studies have shown PBDEs to be thyroid hormone (TH) disruptors. Epidemiologic evidence of PBDE exposure associated with TH disruption has been inconclusive. OBJECTIVES: We used repeated measures to estimate associations between serum PBDE concentrations and THs in a North American adult cohort. METHODS: From 2010 to 2011, we collected <= 3 serum samples at approximately 6-month intervals from 52 healthy adult office workers from Boston, Massachusetts, for analysis of PBDE congeners and THs. RESULTS: The geometric mean sum concentrations of the most prevalent PBDE congeners (BDE-28, BDE-47, BDE-99, BDE-100, and BDE-153) were 22 ng/g lipid in winter 2010, 23 ng/g lipid in summer 2010, and 19 ng/g lipid in winter 2011. BDE 47 was the predominant congener. Based on a multivariable mixed regression model, we estimated that on average, a 1-ng/g serum increase in BDE-47 was associated with a 2.6-MUg/dL decrease in total thyroxine (T4) (95% CI: -4.7, -0.35). Total T4 was inversely associated with each PBDE congener. Serum concentrations of PBDEs were not strongly associated with total triiodothyronine (T3), free T4, or thyroid-stimulating hormone (TSH). CONCLUSION: These results are consistent with those from animal studies showing that exposure to PBDEs is associated with a decrease in serum T4. Because the other TH concentrations did not appear to be associated with BDE exposures, our findings do not indicate effects on the pituitary-thyroid axis. Taken together, our findings suggest that PBDE exposure might decrease the binding of T4 to serum T4 binding proteins. CITATION: Makey CM, McClean MD, Braverman LE, Pearce EN, He XM, Sjodin A, Weinberg JM, Webster TF. 2016. Polybrominated diphenyl ether exposure and thyroid function tests in North American adults. Environ Health Perspect 124:420-425; http://dx.doi.org/10.1289/ehp.1509755. PMID- 26372670 TI - Quantifying Habitual Levels of Physical Activity According to Impact in Older People: Accelerometry Protocol for the VIBE Study. AB - Physical activity (PA) may need to produce high impacts to be osteogenic. The aim of this study was to identify threshold(s) for defining high impact PA for future analyses in the VIBE (Vertical Impact and Bone in the Elderly) study, based on home recordings with triaxial accelerometers. Recordings were obtained from 19 Master Athlete Cohort (MAC; mean 67.6 years) and 15 Hertfordshire Cohort Study (HCS; mean 77.7 years) participants. Data cleaning protocols were developed to exclude artifacts. Accelerations expressed in g units were categorized into three bands selected from the distribution of positive Y-axis peak accelerations. Data were available for 6.6 and 4.4 days from MAC and HCS participants respectively, with approximately 14 hr recording daily. Three-fold more 0.5-1.0g impacts were observed in MAC versus HCS, 20-fold more 1.0-1.5g impacts, and 140-fold more impacts >= 1.5g. Our analysis protocol successfully distinguishes PA levels in active and sedentary older individuals. PMID- 26372671 TI - Barriers to Physical Activity Following Rehabilitation: Perspectives of Older Adults with Chronic Disease. AB - Nonadherence to exercise is a main cause of reduced function for older adults with chronic disease following completion of rehabilitation. This quantitative study used a questionnaire to evaluate the barriers and facilitators to community based exercise following rehabilitation, from the perspectives of older adults with chronic diseases and their healthcare professionals (HCPs). Questionnaires were administered one-on-one to 83 older adults and 35 HCPs. Those with chronic disease perceived cost (43%), travel time (43%), and physical symptoms (39%) as primary barriers to program participation, with similar perceptions across all chronic conditions. Access to a case manager (82%), a supported transition following rehabilitation (78%), and a condition-specific program (78%) were the primary facilitators. Significant between group differences were found between HCPs and older adults with chronic disease across all barriers (p < .001), with a greater number of HCPs perceiving barriers to exercise participation. There were no between-group differences in the perception of factors that facilitate participation in exercise. PMID- 26372672 TI - Design and Fabrication of a Hybrid Superhydrophobic-Hydrophilic Surface That Exhibits Stable Dropwise Condensation. AB - Condensation of water vapor is an essential process in power generation, water collection, and thermal management. Dropwise condensation, where condensed droplets are removed from the surface before coalescing into a film, has been shown to increase the heat transfer efficiency and water collection ability of many surfaces. Numerous efforts have been made to create surfaces which can promote dropwise condensation, including superhydrophobic surfaces on which water droplets are highly mobile. However, the challenge with using such surfaces in condensing environments is that hydrophobic coatings can degrade and/or water droplets on superhydrophobic surfaces transition from the mobile Cassie to the wetted Wenzel state over time and condensation shifts to a less-effective filmwise mechanism. To meet the need for a heat-transfer surface that can maintain stable dropwise condensation, we designed and fabricated a hybrid superhydrophobic-hydrophilic surface. An array of hydrophilic needles, thermally connected to a heat sink, was forced through a robust superhydrophobic polymer film. Condensation occurs preferentially on the needle surface due to differences in wettability and temperature. As the droplet grows, the liquid drop on the needle remains in the Cassie state and does not wet the underlying superhydrophobic surface. The water collection rate on this surface was studied using different surface tilt angles, needle array pitch values, and needle heights. Water condensation rates on the hybrid surface were shown to be 4 times greater than for a planar copper surface and twice as large for silanized silicon or superhydrophobic surfaces without hydrophilic features. A convection conduction heat transfer model was developed; predicted water condensation rates were in good agreement with experimental observations. This type of hybrid superhydrophobic-hydrophilic surface with a larger array of needles is low-cost, robust, and scalable and so could be used for heat transfer and water collection applications. PMID- 26372673 TI - Low-Energy Electron Interaction with the Phosphate Group in DNA Molecule and the Characteristics of Single-Strand Break Pathways. AB - We modeled the low-energy electron attachment to the sugar-phosphate-sugar (SPS) molecule for investigating the single-strand break (3' C-O and 5' C-O) at the DNA backbone. In particular, we predicted the electron capture at the phosphate center. We found that 0.6 eV electron can attach to the phosphate group, and the lifetime (~40-55 fs) of the resulting temporary negative ion state is more than what we found for the lifetime of the metastable species (~18-20 fs) formed at the cytosine base center. We treated the two competing dissociation channels in SPS molecule, that is, both the 3' C-O and 5' C-O lesions, separately. The activation energy barrier calculated for 5' C-O bond rupture is found to be less than that for 3' C-O bond dissociation. The overall low-energy electron transfer process is found to be mediated through a "shape resonance state" formed at the phosphate center. PMID- 26372674 TI - Visible Light Mediated Reductive Cleavage of C-O Bonds Accessing alpha Substituted Aryl Ketones. AB - C-O sigma-bonds in multifaceted benzoin derivatives can be effectively cleaved as acetates using catalytic amounts of [Ru(bpy)3]Cl2 as photoredox catalyst in combination with Hantzsch ester and triethylamine as a sacrificial electron donor. This mild and operationally simple method is applicable to a great variety of substrates. Homo- and cross-benzoins, which are easily accessed by NHC (N heterocyclic carbene) catalysis, with both electron-withdrawing and electron donating substituents, including aryl halogenides, can be employed. The deoxygenated counterparts are isolated in good to excellent yields. These broadly accessible, alpha-substituted (nonsymmetric) aryl ketones are versatilely applicable for further transformations as illustrated by the syntheses of 2 arylbenzofurans. PMID- 26372675 TI - Rational Concept for Designing Vapor-Liquid-Solid Growth of Single Crystalline Metal Oxide Nanowires. AB - Metal oxide nanowires hold great promise for various device applications due to their unique and robust physical properties in air and/or water and also due to their abundance on Earth. Vapor-liquid-solid (VLS) growth of metal oxide nanowires offers the high controllability of their diameters and spatial positions. In addition, VLS growth has applicability to axial and/or radial heterostructures, which are not attainable by other nanowire growth methods. However, material species available for the VLS growth of metal oxide nanowires are substantially limited even though the variety of material species, which has fascinating physical properties, is the most interesting feature of metal oxides. Here we demonstrate a rational design for the VLS growth of various metal oxide nanowires, based on the "material flux window". This material flux window describes the concept of VLS nanowire growth within a limited material flux range, where nucleation preferentially occurs only at a liquid-solid interface. Although the material flux was previously thought to affect primarily the growth rate, we experimentally and theoretically demonstrate that the material flux is the important experimental variable for the VLS growth of metal oxide nanowires. On the basis of the material flux window concept, we discover novel metal oxide nanowires, composed of MnO, CaO, Sm2O3, NiO, and Eu2O3, which were previously impossible to form via the VLS route. The newly grown NiO nanowires exhibited stable memristive properties superior to conventional polycrystalline devices due to the single crystallinity. Thus, this VLS design route offers a useful guideline for the discovery of single crystalline nanowires that are composed of functional metal oxide materials. PMID- 26372676 TI - Growth of epitaxial Pt1-xPbx alloys by surface limited redox replacement and study of their adsorption properties. AB - The surface limited redox replacement (SLRR) method has been used to design two dimensional Pt-Pb nanoalloys with controlled thickness, composition, and structure. The electrochemical behavior of these alloys has been systematically studied as a function of alloy composition. A single-cell, two-step SLRR protocol based on the galvanic replacement of underpotentially deposited monolayers of Pb with Pt was used to grow epitaxial Pt1-xPbx (x < 0.1) alloys of up to 10 ML thickness on Au substrates. It is shown that by varying the terminating potential of the galvanic replacement step, the Pb atomic content can be controlled in the films. Electrochemical analysis of the alloys showed that the adsorption of both H and CO exhibits similar, and systematic, decreases with small increases in the Pb content. These measurements, commonly used in electrocatalysis for the determination of active surface areas of Pt, suggested area values much lower than those expected based on the net Pt composition in the alloy as measured by XPS. These results show that Pb has a strong screening effect on the adsorption of both H and CO. Moreover, changes in alloy composition result in a negative shift in the potential of the peaks of CO oxidation that scales with the increase of Pb content. The results suggest electronic and bifunctional effects of incorporated Pb on the electrochemical behavior of Pt. The study illustrates the potential of the SLRR methodology, which could be employed in the design of 2 dimensional bimetallic Pt nanoalloys for fundamental studies of electrocatalytic behavior in fuel cell reactions dependent on the nature of alloying metal and its composition. PMID- 26372677 TI - Maternal and perinatal outcomes of indicated inductions of labor. AB - PURPOSE: The purpose of this study was to evaluate the labor characteristics and maternal/perinatal consequences following indicated induction of labor. METHODS: This retrospective study examined all of the indicated inductions over 24 months and at two institutions evaluated mode of delivery (vaginal versus cesarean) as well as a comprehensive list of labor characteristics and maternal/perinatal outcomes. RESULTS: There were 1577 indicated inductions with 1097/1577 (69.6%) delivering vaginally. Women with a cesarean delivery had lower parity (p < (0).0001) and Bishop's score (p < (0).0001), and higher body mass indices (p = 0.022). Indication for induction due to preeclampsia increased the risk of a cesarean delivery (p = 0.008). Chorioamnionitis, post-partum complications and NICU admissions were greater in the women delivered by cesarean section. CONCLUSIONS: Indicated inductions which result in cesarean delivery were more likely in women with higher body mass indexes, lower parity, and Bishops scores, as well as preeclampsia. PMID- 26372678 TI - ICS teaching module: Artefacts in urodynamic pressure traces (basic module). AB - AIMS: To present the ICS Teaching Module on artefacts in urodynamics pressure traces. METHODS: Slides from three urodynamics centres were assembled. Descriptions and labels were agreed by the authors and the module presented at the ICS Annual Scientific Meeting in Brazil 2014. RESULTS: Ten artefacts that should be recognized while using water-filled urodynamic systems are presented and remedial action described. CONCLUSIONS: This manuscript serves as scientific background for the slide set made available on the ICS website. By following the guidelines in this teaching module, good quality urodynamics can be more readily achieved. Neurourol. Urodynam. 36:35-36, 2017. (c) 2015 Wiley Periodicals, Inc. PMID- 26372679 TI - Evolving Epidemiology of Staphylococcus aureus Bacteremia. AB - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) infections due to USA300 have become widespread in community and healthcare settings. It is unclear whether risk factors for bloodstream infections (BSIs) differ by strain type. OBJECTIVE: To examine the epidemiology of S. aureus BSIs, including USA300 and non-USA300 MRSA strains. DESIGN: Retrospective observational study with molecular analysis. SETTING: Large urban public hospital. PATIENTS: Individuals with S. aureus BSIs from January 1, 2007 through December 31, 2013. METHODS: We used electronic surveillance data to identify cases of S. aureus BSI. Available MRSA isolates were analyzed by pulsed-field gel electrophoresis. Poisson regression was used to evaluate changes in BSI incidence over time. Risk factor data were collected by medical chart review and logistic regression was used for multivariate analysis of risk factors. RESULTS: A total of 1,015 cases of S. aureus BSIs were identified during the study period; 36% were due to MRSA. The incidence of hospital-onset (HO) MRSA BSIs decreased while that of community onset (CO) MRSA BSIs remained stable. The rate of CO- and HO- methicillin susceptible S. aureus infections both decreased over time. More than half of HO MRSA BSIs were due to the USA300 strain type and for 4 years, the proportion of HO-MRSA BSIs due to USA300 exceeded 60%. On multivariate analysis, current or former drug use was the only epidemiologic risk factor for CO- or HO-MRSA BSIs due to USA300 strains. CONCLUSIONS: USA300 MRSA is endemic in communities and hospitals and certain populations (eg, those who use illicit drugs) may benefit from enhanced prevention efforts in the community. PMID- 26372681 TI - Financial Impact of Liver Sharing and Organ Procurement Organizations' Experience With Share 35: Implications for National Broader Sharing. AB - The Share 35 policy for organ allocation, which was adopted in June 2013, allocates livers regionally for candidates with Model for End-Stage Liver Disease scores of 35 or greater. The authors analyzed the costs resulting from the increased movement of allografts related to this new policy. Using a sample of nine organ procurement organizations, representing 17% of the US population and 19% of the deceased donors in 2013, data were obtained on import and export costs before Share 35 implementation (June 15, 2012, to June 14, 2013) and after Share 35 implementation (June 15, 2013, to June 14, 2014). Results showed that liver import rates increased 42%, with an increased cost of 51%, while export rates increased 112%, with an increased cost of 127%. When the costs of importing and exporting allografts were combined, the total change in costs for all nine organ procurement organizations was $11 011 321 after Share 35 implementation. Extrapolating these costs nationally resulted in an increased yearly cost of $68 820 756 by population or $55 056 605 by number of organ donors. Any alternative allocation proposal needs to account for the financial implications to the transplant infrastructure. PMID- 26372680 TI - Increased YKL-40 and Chitotriosidase in Asthma and Chronic Obstructive Pulmonary Disease. AB - RATIONALE: Serum chitinases may be novel biomarkers of airway inflammation and remodeling, but less is known about factors regulating their levels. OBJECTIVES: To examine serum chitotriosidase activity and YKL-40 levels in patients with asthma and chronic obstructive pulmonary disease (COPD) and evaluate clinically relevant factors that may affect chitinase levels, including genetic variability, corticosteroid treatment, disease exacerbations, and allergen exposure. METHODS: Serum chitotriosidase (CHIT1) activity and YKL-40 (CHI3L1) levels, as well as the CHIT1 rs3831317 and CHI3L1 rs4950928 genotypes, were examined in subsets of patients with mild to moderate asthma (n = 76), severe asthma (n = 93), and COPD (n = 64) taking part in the European multicenter BIOAIR (Longitudinal Assessment of Clinical Course and Biomarkers in Severe Chronic Airway Disease) study. Blood was obtained at baseline, before and after a 2-week oral steroid intervention, up to six times during a 1-year period, and during exacerbations. Baseline chitinase levels were also measured in 72 healthy control subjects. The effect of allergen inhalation on blood and sputum YKL-40 levels was measured in two separate groups of patients with mild atopic asthma; one group underwent repeated low-dose allergen challenge (n = 15), and the other underwent high-dose allergen challenge (n = 16). MEASUREMENTS AND MAIN RESULTS: Serum chitotriosidase and YKL-40 were significantly elevated in patients with asthma and those with COPD compared with healthy control subjects. Genotype and age strongly affected both YKL-40 and chitotriosidase activity, but associations with disease remained following adjustment for these factors. Correlations were observed with lung function but not with other biomarkers, including exhaled nitric oxide, blood eosinophils, periostin, and IgE. Generally, acute exacerbations, allergen-induced airway obstruction, and corticosteroid treatment did not affect circulating chitinase levels. CONCLUSIONS: YKL-40 and chitotriosidase are increased in asthma and more so in COPD. The data in the present study support these substances as being relatively steroid-insensitive, non-T-helper cell type 2-type biomarkers distinctly related to chronic inflammatory disease processes. PMID- 26372682 TI - Inter- and intragranular delta phase quantitative characterization in Inconel 718 by means of image analysis. AB - This paper describes an image processing method for discriminating the inter- and intragranular delta phase precipitates in Inconel 718 (IN 718). The successive practical operations and the motivations of their choices are presented in detail. The method was applied to IN 718 specimens heat treated with different parameters to produce microstructures containing various amounts of both types of precipitates. They were characterized by electron microscopy in backscattered electron imaging. The main difficulty arose from the fact that the brightness distributions of inter- and intragranular precipitates partially overlap. Additional information on their morphology and their spatial distribution had to be exploited in order to differentiate them. The shape and the orientation of the precipitates were evaluated using the structure tensor, an operator that quantifies the directionality of the intensity distribution in an image. The distance between parallel precipitates was also used as an additional property to identify clusters of intragranular precipitates. PMID- 26372683 TI - Adipofascial Anterolateral Thigh Free Flaps for Oncologic Hand and Foot Reconstruction. PMID- 26372684 TI - Submental Artery Flap with Sentinel Lymph Node Biopsy in the Reconstruction of Oral Cancer. AB - BACKGROUND: Microvascular free flaps form the gold standard for reconstruction of defects after intraoral cancer surgery, but not all patients are suitable candidates for microsurgery. The submental artery flap is an alternative to free tissue transfer especially in patients who do not tolerate extensive operations due to major comorbidities. However, in metastatic neck disease, this option has not been recommended due to theoretical intraoral transfer of cancer cells. The aim of this study was to consider the indications and benefits of the submental artery perforator flap in patients with intraoral cancer. METHODS: Ten patients with early (N = 2) or locally advanced (N = 8) intraoral cancer, who were not candidates for free tissue transfer because of major comorbidities, were managed with tumor resection and coverage of the defect with the submental artery flap. The minimum follow-up time for all patients was 6 years. RESULTS: The average defect size was 5 * 9 cm. Two patients developed major complications and one of them had a flap loss. Sentinel lymph node biopsy was used in three cases to rule out positive neck disease close to the flap pedicle. During the follow-up time 6 out of 10 patients had a local recurrence and there were no appearances of metastatic neck disease. CONCLUSION: The submental artery flap is an alternative option to intraoral microvascular reconstruction in patients with major comorbidities. Sentinel lymph node biopsy can be used as an adjunct to enhance oncological safety. PMID- 26372685 TI - Venous Thrombosis in Handsewn versus Coupled Venous Anastomoses in 857 Consecutive Breast Free Flaps. AB - BACKGROUND: The anastomotic coupling device has demonstrated safety and efficacy; however, the coupler has never been compared directly to handsewn venous anastomoses exclusively in breast reconstruction. We hypothesized that rates of venous thrombosis would be lower using the coupler versus handsewn anastomoses in free flap breast reconstruction. METHODS: We performed a retrospective review utilizing clinic records, hospital records, and operative reports for 857 consecutive breast free flaps at a single institution from 1997 to 2012. Data were collected on reconstruction type, recipient vessels, timing, laterality, preoperative radiation, chemotherapy, venous thrombosis, and flap outcome. We compared rates of venous thrombosis between handsewn and coupled anastomoses for breast free flaps. Chi-square test was used to calculate statistical significance. RESULTS: A total of 857 consecutive free flaps were performed for breast reconstruction in 647 patients over 16 years. The venous anastomosis was handsewn in 303 flaps, and the anastomotic coupler was used in 554 flaps. The rate of venous thrombosis requiring anastomotic revision in the handsewn group was 0.04% (12/303), compared with 0.01% in the coupled group (8/554; p = 0.02). CONCLUSION: The anastomotic coupler was more effective in preventing venous thrombosis than handsewn anastomoses in our series. While our study demonstrates improved patency rates using the venous coupler in breast reconstruction, we were unable to definitively separate this finding from potential confounding variables due to the low rates of thrombosis in both the groups. Our data are consistent with current literature, which suggests that the coupler is a safe and effective alternative to hand sutured anastomoses. PMID- 26372686 TI - Microanatomy of the Separable Length of the C7. AB - OBJECTIVE: The objective of this study was to provide anatomical data on modified contralateral C7 (cC7) nerve root transfers by dissecting and measuring the separable lengths of the C7 root, trunk, and divisions. MATERIALS AND METHODS: Fifteen adult cervicothoracic specimens were dissected and measured using Vernier calipers after exposing the brachial plexus. Measurements included the length of the C7 from the root to the trunk, the lengths of the C7 root-trunk-anterior division (and posterior division). The epineuria at the C7 root-division-cord junctions were opened until the internal nerve bundles fused together and could not be separated by microdissection. The lengths of the C7 root-trunk-anterior (and posterior) division were measured again after microdissection. The lengths of cC7 nerve of 20 patients with bracial plexus avulsion were measured using the former technique. RESULTS: The length of the C7 root-trunk was 45.87 SD 10.43 mm. Before separation, the lengths of the C7 root-trunk-anterior division and the root-trunk-posterior division were 61.14 SD 13.44 and 54.63 SD 11.35 mm, respectively; after separation, the lengths were 74.67 SD 12.86 and 68.73 SD 11.86 mm, respectively. The prolonged lengths were 13.15 SD 4.26 and 14.21 SD 6.98 mm, respectively. The prolonged lengths were significantly greater (p < 0.05). The prolonged length of C7 nerve clinically was anterior division, 15.30 SD 3.76 mm and posterior division, 11.10 SD 3.01 mm. CONCLUSION: The C7 division lengths can be prolonged by dissecting the epineuria at the division-cord junction of the C7 nerve root. PMID- 26372687 TI - Spontaneous Reinnervation of Deep Inferior Epigastric Perforator Flaps after Delayed Breast Reconstruction. AB - BACKGROUND: The spontaneous reinnervation of free flaps, such as deep inferior epigastric perforator (DIEP) flaps, is not fully understood, and few publications have investigated this issue. The aim of this study was to examine spontaneous reinnervation following breast reconstruction with autologous DIEP flaps without an additional nerve transfer. METHODS: In a retrospective clinical study, 18 female patients were investigated for a mean of 49.59 months (range, 12-88 months) following breast reconstruction with a unilateral DIEP flap. Five sensory modalities were tested: pressure perception, dynamic two-point discrimination, sharp-blunt discrimination, hot and cold discrimination, and vibration perception threshold (VPT). The measurements were performed on the reconstructed breast, flap surrounding transition zone, healthy contralateral breast, and the donor site. For a more precise analysis all breasts have been divided into five different segments (mediocranial, laterocranial, mediocaudal, laterocaudal, and reconstructed nipple-areola complex, if present). Additionally, tissue oxygen saturation and tissue hemoglobin were measured by laser Doppler spectroscopy. RESULTS: Spontaneous reinnervation of at least one modality tested was observed in all DIEP flaps (n = 18). This sensitive recovery increases over the postoperative period. The maximum difference between the controls and DIEP flaps was observed in cold perception, whereas the least difference was observed in the VPT. Regarding the different segments, we observed better sensitive recovery in the cranial parts of the DIEP flaps and the transition zone. CONCLUSION: This study provides certain predictions for patients and surgeons, when and to which extent spontaneous reinnervation can be expected. PMID- 26372688 TI - Autologous Lymph Node Transfers. AB - Lymphedema is a common chronic and progressive condition complicating cancer treatment. Patients undergoing lymph node dissection and radiation therapy required for oncological treatment in breast and pelvic cancers are at high risk for secondary lymphedema. Reconstruction of the damaged region with a fatty flap containing lymph nodes may restore the anatomy. It has been postulated that the cytokines included in the fat surrounding the nodes VEGF-c allow regrowth of the lymphatic vessels. Hypoplasic congenital lymphedema are also positively improved by the autologous lymph node transfer, thanks to the same principles. PMID- 26372689 TI - Retinoic Acid Induces Ubiquitination-Resistant RIP140/LSD1 Complex to Fine-Tune Pax6 Gene in Neuronal Differentiation. AB - Receptor-interacting protein 140 (RIP140) is a wide-spectrum coregulator for hormonal regulation of gene expression, but its activity in development/stem cell differentiation is unknown. Here, we identify RIP140 as an immediate retinoic acid (RA)-induced dual-function chaperone for LSD1 (lysine-specific demethylase 1). RIP140 protects LSD1's catalytic domain and antagonizes its Jade-2-mediated ubiquitination and degradation. In RA-induced neuronal differentiation, the increased RIP140/LSD1 complex is recruited by RA-elevated Pit-1 to specifically reduce H3K4me2 modification on the Pax6 promoter, thereby repressing RA-induction of Pax6. This study reveals a new RA-induced gene repressive mechanism that modulates the abundance, enzyme quality, and recruitment of histone modifier LSD1 to neuronal regulator Pax6, which provides a homeostatic control for RA induction of neuronal differentiation. PMID- 26372690 TI - Development of Statistical Methods for Analytical Similarity Assessment. AB - To evaluate the analytical similarity between the proposed biosimilar product and the US-licensed reference product, U.S. Food and Drug Administration (FDA) statisticians collaborated with Chemistry, Manufacturing and Control (CMC) scientists at FDA in order to develop a three-tier approach. The proposed tiered approach starts with a criticality determination of quality attributes (QAs) based on their potential impact on product quality and the clinical outcomes. Those QAs characterize the biological product in terms of structural, physico chemical, and functional properties. Then, the QAs are assigned into three tiers based on their criticality ranking. To evaluate the analytical similarity for QAs assigned to different tiers, we recommend different statistical approaches with different statistical rigors. That is, we recommend an equivalence test for the critical quality attributes (CQAs) in Tier 1, a quality range approach for QAs in Tier 2, and a side-by-side graphic comparison approach for QAs in Tier 3. In this article, we mainly focus on the development of the FDA's recommended equivalence test for Tier 1. We also provide some discussion on the statistical challenges of the proposed equivalence test in the context of analytical similarity assessment. PMID- 26372691 TI - Patent cliff mitigation strategies: giving new life to blockbusters. AB - With several blockbuster drugs on the brink of another significant patent expiry cliff, innovator pharmaceutical firms are at risk of losing billions of dollars in sales to generic competition. With issues such as staggering R&D costs, reduced productivity and increasing governmental emphasis on pharmacoeconomics, timely planning and implementation of product lifecycle management strategies is becoming indispensable. A variety of strategies designed to mitigate the post patent expiry revenue loss exist. These approaches range from fairly straightforward measures, such as strategic price cuts and launching own or authorized generics, to complex and lengthy ones, such as new formulations and indications that require companies to reinvent their pharmaceuticals. As patent expiries loom and product pipelines continue to remain thin, proactive planning for generic entry will be critical for pharma companies to drive growth and earnings in a sustainable manner. PMID- 26372692 TI - Comparing Subjective With Objective Sleep Parameters Via Multisensory Actigraphy in German Physical Education Students. AB - This study compared subjective with objective sleep parameters among 72 physical education students. Furthermore, the study determined whether 24-hr recording differs from nighttime recording only. Participants wore the SenseWear ArmbandTM for three consecutive nights and kept a sleep log. Agreement rates ranged from moderate to low for sleep onset latency (ICC = 0.39 to 0.70) and wake after sleep onset (ICC = 0.22 to 0.59), while time in bed (ICC = 0.93 to 0.95) and total sleep time (ICC = 0.90 to 0.92) revealed strong agreement during this period. Comparing deviations between 24-hr wearing time (n = 24) and night-only application (n = 20) revealed no statistical difference (p > 0.05). As athletic populations have yet to be investigated for these purposes, this study provides useful indicators and practical implications for future studies. PMID- 26372693 TI - Carbohydrate-based vaccine adjuvants - discovery and development. AB - INTRODUCTION: The addition of a suitable adjuvant to a vaccine can generate significant effective adaptive immune responses. There is an urgent need for the development of novel po7tent and safe adjuvants for human vaccines. Carbohydrate molecules are promising adjuvants for human vaccines due to their high biocompatibility and good tolerability in vivo. AREAS COVERED: The present review covers a few promising carbohydrate-based adjuvants, lipopolysaccharide, trehalose-6,6'-dibehenate, QS-21 and inulin as examples, which have been extensively studied in human vaccines in a number of preclinical and clinical studies. The authors discuss the current status, applications and strategies of development of each adjuvant and different adjuvant formulation systems. This information gives insight regarding the exciting prospect in the field of carbohydrate-based adjuvant research. EXPERT OPINION: Carbohydrate-based adjuvants are promising candidates as an alternative to the Alum salts for human vaccines development. Furthermore, combining two or more adjuvants in one formulation is one of the effective strategies in adjuvant development. However, further research efforts are needed to study and develop novel adjuvants systems, which can be more stable, potent and safe. The development of synthetic carbohydrate chemistry can improve the study of carbohydrate-based adjuvants. PMID- 26372695 TI - Identification of AFB1-interacting proteins and interactions between RPSA and AFB1. AB - A method using immobilized affinity chromatography (IAC) was developed to screen for aflatoxin B1 (AFB1)-binding proteins. AFB1 and bovine serum albumin (BSA) coupled protein (BSA-AFB1) was prepared using 1-ethyl-3-(3 dimethylaminopropyl)carbodiimide hydrochloride. The resulting coupled compound was immobilized onto PVDF transfer membranes, which were then incubated with total protein from mouse liver. AFB1-binding proteins were eluted, after non specific washing, by specific elution, and the eluted proteins were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Two candidate AFB1 binding proteins were identified by liquid chromatography-tandem mass spectrometry as the 40S ribosomal protein SA (RPSA) and a putative uncharacterized protein. RPSA and AFB1 interactions were further analyzed by ELISA in vitro and laser confocal immunofluorescence analysis in vivo. The results from ELISA and immunofluorescence showed that RPSA efficiently bound AFB1 in vitro and in vivo. This study's conclusion laid the foundation for further exploration of the role of AFB1-binding proteins in AFB1 toxicology towards hepatocytes and the entry pathway of AFB1 into hepatocytes. PMID- 26372694 TI - Health impact metrics for air pollution management strategies. AB - Health impact assessments (HIAs) inform policy and decision making by providing information regarding future health concerns, and quantitative HIAs now are being used for local and urban-scale projects. HIA results can be expressed using a variety of metrics that differ in meaningful ways, and guidance is lacking with respect to best practices for the development and use of HIA metrics. This study reviews HIA metrics pertaining to air quality management and presents evaluative criteria for their selection and use. These are illustrated in a case study where PM2.5 concentrations are lowered from 10 to 8MUg/m(3) in an urban area of 1.8 million people. Health impact functions are used to estimate the number of premature deaths, unscheduled hospitalizations and other morbidity outcomes. The most common metric in recent quantitative HIAs has been the number of cases of adverse outcomes avoided. Other metrics include time-based measures, e.g., disability-adjusted life years (DALYs), monetized impacts, functional-unit based measures, e.g., benefits per ton of emissions reduced, and other economic indicators, e.g., cost-benefit ratios. These metrics are evaluated by considering their comprehensiveness, the spatial and temporal resolution of the analysis, how equity considerations are facilitated, and the analysis and presentation of uncertainty. In the case study, the greatest number of avoided cases occurs for low severity morbidity outcomes, e.g., asthma exacerbations (n=28,000) and minor restricted activity days (n=37,000); while DALYs and monetized impacts are driven by the severity, duration and value assigned to a relatively low number of premature deaths (n=190 to 230 per year). The selection of appropriate metrics depends on the problem context and boundaries, the severity of impacts, and community values regarding health. The number of avoided cases provides an estimate of the number of people affected, and monetized impacts facilitate additional economic analyses useful to policy analysis. DALYs are commonly used as an aggregate measure of health impacts and can be used to compare impacts across studies. Benefits per ton metrics may be appropriate when changes in emissions rates can be estimated. To address community concerns and HIA objectives, a combination of metrics is suggested. PMID- 26372696 TI - Cd-induced oxidative stress and lignification in the roots of two Vicia sativa L. varieties with different Cd tolerances. AB - We examined the effects of Cd on growth, lipid peroxidation, reactive oxygen species (ROS) accumulation, antioxidant enzymatic activity, and lignin content in the roots of two varieties of Vicia sativa. Treatment with Cd decreased plant growth and increased ROS and lipid peroxidation levels to a greater extent in the Cd-sensitive variety ZM than in the Cd-tolerant variety L3. Most hydrogen peroxide (H2O2) and superoxide anion (O2(*-)) were accumulated in the cell walls and extracellular spaces in response to Cd treatments. Chemical assays and experiments using inhibitors showed that larger increases in H2O2 and O2(*-) production in ZM than in L3 were probably attributed to elevated Cd-induced nicotinamide adenine dinucleotide-peroxidase (NADH-POD) activity. Cd treatment increased the accumulation of lignin and the guaiacol peroxidase (GPOD) activities in the apoplast more significantly in ZM root than in L3. Howerver, root laccase activity was higher in L3 than in ZM. Thus Cd toxicity induced significant lignification in the roots of V. sativa, and increases in H2O2 accumulation and apoplastic GPOD activity were likely responsible for this effect. PMID- 26372697 TI - Acquired resistance to anti-EGFR mAb ICR62 in cancer cells is accompanied by an increased EGFR expression, HER-2/HER-3 signalling and sensitivity to pan HER blockers. AB - BACKGROUND: The human epidermal growth factor receptor (EGFR) is an important target for cancer treatment. Currently, only the EGFR antibodies cetuximab and panitumumab are approved for the treatment of patients with colorectal cancer. However, a major clinical challenge is a short-term response owing to development of acquired resistance during the course of the treatment. METHODS: In this study, we investigated the molecular mechanisms underlying development of acquired resistance in DiFi colorectal cancer cells to the anti-EGFR mAb ICR62 (termed DiFi62) and to the small molecule tyrosine kinase inhibitor (TKI) gefitinib (termed DiFiG) using a range of techniques. RESULTS: Compared with the findings from parental DiFi and DiFiG cells, development of acquired resistance to anti-EGFR mAb ICR62 in DiFi62 cells was accompanied by an increase in cell surface EGFR and increased phosphorylation of HER-2 and HER-3. Interestingly, DiFi62 cells also acquired resistance to treatment with anti-EGFR mAbs cetuximab and ICR61, which bind to other distinct epitopes on the extracellular domain of EGFR, but these cells remained equally sensitive as the parental cells to treatment with pan-HER inhibitors such as afatinib. CONCLUSIONS: Our results provide a novel mechanistic insight into the development of acquired resistance to EGFR antibody-based therapy in colorectal cancer cells and justify further investigations on the therapeutic benefits of pan-HER family inhibitors in the treatment of colorectal cancer patients once acquired resistance to EGFR antibody based therapy is developed. PMID- 26372698 TI - A serum metabolomic fingerprint of bevacizumab and temsirolimus combination as first-line treatment of metastatic renal cell carcinoma. AB - BACKGROUND: Renal cell carcinoma is one of the most chemoresistant cancers, and its metastatic form requires administration of targeted therapies based on angiogenesis or mTOR inhibitors. Understanding how these treatments impact the human metabolism is essential to predict the host response and adjust personalised therapies. We present a metabolomic investigation of serum samples from patients with metastatic RCC (mRCC) to identify metabolic signatures associated with targeted therapies. METHODS: Pre-treatment and serial on treatment sera were available for 121 patients participating in the French clinical trial TORAVA, in which 171 randomised patients with mRCC received a bevacizumab and temsirolimus combination (experimental arm A) or a standard treatment: either sunitinib (B) or interferon-alpha+bevacizumab (C). Metabolic profiles were obtained using nuclear magnetic resonance spectroscopy and compared on-treatment or between treatments. RESULTS: Multivariate statistical modelling discriminates serum profiles before and after several weeks of treatment for arms A and C. The combination A causes faster changes in patient metabolism than treatment C, detectable after only 2 weeks of treatment. Metabolites related to the discrimination include lipids and carbohydrates, consistently with the known RCC metabolism and side effects of the drugs involved. Comparison of the metabolic profiles for the three arms shows that temsirolimus, an mTOR inhibitor, is responsible for the faster host metabolism modification observed in the experimental arm. CONCLUSIONS: In mRCC, metabolomics shows a faster host metabolism modification induced by a mTOR inhibitor as compared with standard treatments. These results should be confirmed in larger cohorts and other cancer types. PMID- 26372699 TI - Comment on: 'KRAS and BRAF mutations are prognostic biomarkers in patients undergoing lung metastasectomy of colorectal cancer.' Variation in survival associated with proto-oncongenes is not evidence for effectiveness of lung metastasectomy. PMID- 26372700 TI - Aspirin as a neoadjuvant agent during preoperative chemoradiation for rectal cancer. AB - BACKGROUND: Recently, many studies have suggested a possible adjuvant role of aspirin in colorectal cancer, reporting a positive prognostic effect with its use in patients with established disease. The aim of this study was to investigate the anticancer effect of aspirin use during preoperative chemoradiation for rectal cancer. METHODS: Two hundred and forty-one patients with stage II-III rectal cancer and candidates for chemoradiation (CRT) were selected and assigned to two groups: group 1, patients taking aspirin at the time of diagnosis, and group 2, all others. Treatment and oncological outcomes were explored. RESULTS: Aspirin use was associated with a higher rate of tumour downstaging (67.6% vs 43.6%, P=0.01), good pathological response (46% vs 19%; P<0.001), and a slightly, although not significant, higher rate of complete pathological response (22% vs 13%; P=0.196). Aspirin use was also associated with a better 5-year progression free survival (86.6% vs 67.1%; hazard rate (HR)=0.20; 95% CI=0.07-0.60) and overall survival (90.6% vs 73.2%; HR=0.21; 95% CI=0.05-0.89). Although chance of local relapse was similar (HR=0.6; 95% CI=0.06-4.5), aspirin use was associated with a lower risk of developing metastasis (HR=0.30; 95% CI=0.10-0.86). CONCLUSIONS: Aspirin might have anticancer activity against rectal cancer during preoperative CRT. This finding could be clinically relevant and should be further investigated with randomised trials. PMID- 26372702 TI - Reply: Comment on 'KRAS and BRAF mutations are prognostic biomarkers in patients undergoing lung metastasectomy of colo-rectal cancer'. PMID- 26372701 TI - Nab-paclitaxel plus gemcitabine for metastatic pancreatic adenocarcinoma after Folfirinox failure: an AGEO prospective multicentre cohort. AB - BACKGROUND: There is currently no standard second-line treatment for metastatic pancreatic adenocarcinoma (MPA), and progression-free survival is consistently <4 months in this setting. The aim of this study was to evaluate the efficacy and tolerability of Nab-paclitaxel plus gemcitabine (A+G) after Folfirinox failure in MPA. METHODS: From February 2013 to July 2014, all consecutive patients treated with A+G for histologically proven MPA after Folfirinox failure were prospectively enrolled in 12 French centres. A+G was delivered as described in the MPACT trial, until disease progression, patient refusal or unacceptable toxicity. RESULTS: Fifty-seven patients were treated with Nab-paclitaxel plus gemcitabine, for a median of 4 cycles (range 1-12). The disease control rate was 58%, with a 17.5% objective response rate. Median overall survival (OS) was 8.8 months (95% CI: 6.2-9.7) and median progression-free survival was 5.1 months (95% CI: 3.2-6.2). Since the start of first-line chemotherapy, median OS was 18 months (95% CI: 16-21). No toxic deaths occurred. Grade 3-4 toxicities were reported in 40% of patients, consisting of neutropenia (12.5%), neurotoxicity (12.5%), asthenia (9%) and thrombocytopenia (6.5%). CONCLUSIONS: A+G seems to be effective, with a manageable toxicity profile, after Folfirinox failure in patients with MPA. PMID- 26372704 TI - Contemporary Management of Facial Trauma. PMID- 26372705 TI - Airway Management in Facial Trauma Patients. AB - Airway management in craniofacial trauma patients is a challenge for an anesthetist. Treating these patients requires a close interdisciplinary communication and cooperation. Maintaining the airway and oxygenation of the patient is the initial challenge in craniofacial trauma patients. The management of the difficult airway is facilitated and patient's safety improved by following one of several published difficult airway algorithms. We describe the St. Gallen difficult airway algorithm for the management of difficult airway in general and the airway in facial trauma patients in particular. Whenever possible, the airway should be secured in a conscious and spontaneously breathing patient. It is important to be familiar with different techniques and to change the approach after two unsuccessful attempts with one technique. Once the airway is established, all available preventive measures should be used to avoid losing the airway. A tracheotomy has its place in a significant number of patients in whom an immediate postoperative or a delayed extubation appears unfeasible. PMID- 26372703 TI - Prognostic value of the KRAS G12V mutation in 841 surgically resected Caucasian lung adenocarcinoma cases. AB - BACKGROUND: Identifying patients who will experience lung cancer recurrence after surgery remains a challenge. We aimed to evaluate whether mutant forms of epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene homolog (KRAS) (mEGFR and mKRAS) are useful biomarkers in resected non-small cell lung cancer (NSCLC). METHODS: We retrospectively reviewed data from 841 patients who underwent surgery and molecular testing for NSCLC between 2007 and 2012. RESULTS: mEGFR was observed in 103 patients (12.2%), and mKRAS in 265 (31.5%). The median overall survival (OS) and time to recurrence (TTR) were significantly lower for mKRAS (OS: 43 months; TTR: 19 months) compared with mEGFR (OS: 67 months; TTR: 24 months) and wild-type patients (OS: 55 months; disease-free survival (DFS): 24 months). Patients with KRAS G12V exhibited worse OS and TTR compared with the entire cohort (OS: KRAS G12V: 26 months vs COHORT: 60 months; DFS: KRAS G12V: 15 months vs COHORT: 24 months). These results were confirmed using multivariate analyses (non-G12V status, hazard ratio (HR): 0.43 (confidence interval: 0.28-0.65), P<0.0001 for OS; HR: 0.67 (0.48-0.92), P=0.01 for TTR). Risk of recurrence was significantly lower for non-KRAS G12V (HR: 0.01, (0.001 0.08), P<0.0001). CONCLUSIONS: mKRAS and mEGFR may predict survival and recurrence in early stages of NSCLC. Patients with KRAS G12V exhibited worse OS and higher recurrence incidences. PMID- 26372706 TI - Neurosurgical and Intensive Care Management of Traumatic Brain Injury. AB - Optimal management of patients with traumatic brain injury (TBI) remains a challenge, despite significant improvements in pathophysiologic understanding and treatment strategies in recent decades. Because primary brain injury sustained at the time of trauma is irreversible, the TBI management mainly aims for early detection and treatment of secondary brain injury such as space-occupying intracerebral hematomas and brain edema. Prevention of secondary brain injury requires a high standard of care and understanding of both medical and surgical treatment modalities. This review focuses on practical recommendations for neurosurgical and intensive care management in patients with severe TBI. PMID- 26372707 TI - Frontobasal Fractures. AB - Frontobasal fractures occur in up to 24% of head injuries and often require a multidisciplinary approach. Besides the common bone fractures, the complex anatomy can cause damage to the sense of vision and smell. Further possibly lethal complications such as cerebrospinal fluid leak followed by meningitis or internal carotid bleeding can follow. Diagnostic and treatment options are reviewed with a focus on the endoscopic endonasal approach. PMID- 26372708 TI - Emergency Treatment of Ocular Trauma. AB - Injuries to the eye and its adnexa are common in head and neck trauma centers. An ophthalmologist experienced in ocular traumatology is not always available. Therefore, every emergency physician should be familiar with the basic evaluation, triage, and management of ocular trauma. Above all, the identification of a need for immediate treatment should be implemented in the algorithm of an emergency room, especially in a head and neck trauma center, to reduce the risk of a devastating loss of vision. This article formulates the different types of ocular trauma and their required first-line therapy. PMID- 26372709 TI - Maxillofacial Fractures: Midface and Internal Orbit-Part I: Classification and Assessment. AB - Fractures of the midface and internal orbit occur isolated or in combination with other injuries. Frequently, the patients are first seen in emergency rooms responsible for the coordination of initial diagnostic procedures, followed by the transfer to specialties for further treatment. It is, therefore, important for all physicians treating facial trauma patients to understand the basic principles of injuries to the midface. Thus, this article aims to describe the anatomy and the current classification systems in use, the related clinical symptoms, and the essential diagnostic measures to obtain precise information about the injury pattern. PMID- 26372710 TI - Maxillofacial Fractures: Midface and Internal Orbit-Part II: Principles and Surgical Treatment. AB - Current clinical assessment and imaging techniques were described in part 1, and this article presents a systematic review of the surgical treatment principles in the management of midface and internal orbit fractures from initial care to definitive treatment, including illustrative case examples. New developments enabled limited surgical approaches by standardization of osteosynthesis principles regarding three-dimensional buttress reconstruction, by newly developed individualized implants such as titanium meshes and, especially for complex fracture patterns, by critical assessment of anatomical reconstruction through intraoperative endoscopy, as well as intra- and postoperative imaging. Resorbable soft tissue anchors can be used both for ligament and soft tissue resuspension to reduce ptosis effects in the cheeks and nasolabial area and to achieve facial aesthetics similar to those prior to the injury. PMID- 26372711 TI - Management of Zygomatic Fractures: Bone and Arch. AB - Zygomatic bone and arch fractures are among the most common facial fractures treated by facial plastic surgeons. Controversy still remains regarding the optimal management of these fractures. Computed tomographic scanning (including three-dimensional reconstruction) represent a fundamental tool for diagnosis and treatment planning of zygomatic fractures. Main indications for treatment are functional impairment, cosmetic deformity, or both. Fracture reduction can be performed through an open or closed approach depending on the amount of exposure necessary to achieve accurate reduction. The common goal among all treatment plans is the exact three-dimensional restoration of the disturbed anatomy and function while minimizing complications. PMID- 26372712 TI - Penetrating Trauma to the Parotid Gland. AB - Penetrating trauma to the parotid gland may present unique challenges especially when Stensen duct, neurovascular structures, and/or collateral organs are involved. Especially ballistic injuries caused by high-velocity projectiles or fragments of grenades and improvised explosive devices are often associated with massive tissue damage and a high risk of infections and other posttraumatic complications. Because penetrating parotid trauma is not very common, only limited information on the primary treatment of such injuries is available. This article gives a short overview about actual aspects on diagnosis and treatment strategies especially focusing on ballistic parotid injuries. PMID- 26372713 TI - Trauma Management of the Auricle. AB - Smaller injuries of the auricle, such as lacerations without tissue loss, have more or less standardized treatment protocols that require thorough wound closure of each affected layer. Even extended lacerations of larger parts of the ear quite often heal with only minor irregularities. New in vivo diagnostic tools have aided the understanding of this outstanding "skin flap behavior." At the other end of the trauma severity spectrum are partial or complete amputations of the ear. Here, the debate has become more intense over the last decade. There were numerous reports of successful microvascular reattachments in the 1990s. Consequently, pocket methods and their variations have received increasing attention because the results seem to be convincing. Nevertheless, the pressure damage due to banking larger parts of the elastic cartilage in the mastoid region is tremendous, and the tissue for secondary reconstruction is severely injured. Particularly in cases of acute trauma with relevant concomitant injuries to the patient and in cases in which the amputated area is in a critical state, direct wound closure is a straightforward and safe option. Subsequent thoughtfully planned secondary reconstruction using ear or rib cartilage, or even allogenous material as an ear framework, can achieve excellent aesthetic results. PMID- 26372714 TI - Current Strategies in the Treatment of Scars and Keloids. AB - Hypertrophic scars (HTSs) and keloids are a major health concern for aesthetic and functional reasons. Despite a plethora of rapidly evolving treatment options and technical advances, the management of pathologic scarring remains difficult. The development of standardized treatment algorithms has been problematic for years due to the lack of sound randomized controlled trials. Expert panels are more and more establishing guidelines to provide an evidence-based framework on a national and international level. This article aims to evaluate the current strategies and upcoming trends in the therapy and prevention of unpleasant scars and keloids from a clinical perspective. There is strong evidence to support a growing role of early combination treatments, particularly the application of 5 fluoruracil adjunct to intralesional steroid injections. Furthermore, the use of fractional ablative laser technologies such as the CO2 laser has recently yielded promising results with respect to aesthetic outcomes and patient satisfaction at tolerable side effects. PMID- 26372715 TI - Posttraumatic Stress Disorder: Reason for or Consequence of Facial Plastic Surgery? AB - Facial plastic surgery may be undertaken for a variety of reasons. Patients may have had traumatic experiences prior to surgery, such as an accident, a physical assault, or severe illness resulting in facial damage, and they may have used inadequate coping strategies. These patients usually appear suspicious toward medical staff and need special attention because they are at high risk of being unsatisfied with the outcome of surgery. Some patients may hold unrealistic assumptions about the outcome of plastic surgery. Yet other patients may suffer from complications of surgery and may thus experience facial plastic surgery as a trauma. In all such events these patients require special attention. First of all, careful exploration of traumatic experiences prior to surgery should take place even if this does not seem to be part of the standard treatment and requires additional time. Patients usually experience strong relief when their concerns are taken seriously, and treatment outcomes can thus be improved. Moreover, patients should be checked for acute stress disorder (ASD) or posttraumatic stress disorder (PTSD), and if so diagnosed, specialized treatment should be initiated postoperatively. Patients with ASD or PTSD will experience the surgical intervention and the treatment postsurgery with more confidence and greater satisfaction if the surgeon also engages in the psychosocial aspects of their history. PMID- 26372716 TI - The Effect of Liquid Nitrogen on Bone Graft Survival. AB - Liquid nitrogen is used in medicine for cancer treatment and tissue preservation; however, bone viability after its application is controversial. This study aims to evaluate both the tissue viability and the clinical and histopathologic findings following liquid nitrogen application with different thawing techniques in rats. Mandibular bone grafts were taken from 45 Wistar rats and freezed in liquid nitrogen for 20 minutes. In the rapid-thawing technique (Rapid Thawing-1, Rapid Thawing-2), the grafts were held for 20 minutes in room temperature; in the slow-thawing technique (Slow Thawing-1, Slow Thawing-2), 20 minutes in -20 degrees C, 20 minutes in +4 degrees C, and 20 minutes in room temperature, respectively. In Rapid Thawing-2 and Slow Thawing-2 groups, autografts were implanted to their origin for 3 weeks and bone staining with India ink was performed and samples taken for histologic examination. The amount of cells and blood vessels and the density of bone canaliculi were significantly reduced in Rapid Thawing-1 and Slow Thawing-1 groups comparing to the Control group. However, the reduction rate was more significant in the Slow Thawing-1 group. Histomorphometric evaluation of the healing autografts after 3 weeks revealed that the decreased amounts of canaliculi were not changed in Slow Thawing-2 group. The study results demonstrated that bone tissue survives after liquid nitrogen treatment regardless of the performed thawing technique; however, slow thawing causes more tissue damage and metabolism impairment. PMID- 26372717 TI - An Inferiorly Based Rotation Flap for Defects Involving the Lower Eyelid and Medial Cheek. AB - We report a series of 20 patients who underwent inferiorly based rotation flaps for reconstruction of defects of the medial and infraorbital cheek and lower eyelid following Mohs micrographic surgery for nonmelanoma skin cancer. Defects ranged from 1.2 to 3.2 cm in longest diameter and patients ranged from 27 to 91 years of age. All 20 patients had excellent functional and cosmetic outcome with up to 2-year follow-up and no subsequent surgical or laser revision. There were no instances of partial or complete flap necrosis, hematoma, or ectropion. Our series includes defects that originated on the cheek as far laterally as directly below the lateral canthus, and terminated as far medially as the nasal sidewall. An inferiorly based rotation flap is a viable alternative to a laterally based rotation flap and should be in the armamentarium of reconstructive dermatologic and facial plastic surgeons. PMID- 26372718 TI - An Easy and Practical Method for Centrifuge under Sterile Settings in Fat Injection Process. PMID- 26372719 TI - Combining Nuclear Magnetic Resonance Spectroscopy and Density Functional Theory Calculations to Characterize Carvedilol Polymorphs. AB - The experiments of carvedilol form II, form III, and hydrate by (13)C and (15)N cross-polarization magic-angle spinning (CP MAS) are reported. The GIPAW (gauge including projector-augmented wave) method from DFT (density functional theory) calculations was used to simulate (13)C and (15)N chemical shifts. A very good agreement was found for the comparison between the global results of experimental and calculated nuclear magnetic resonance (NMR) chemical shifts for carvedilol polymorphs. This work aims a comprehensive understanding of carvedilol crystalline forms employing solution and solid-state NMR as well as DFT calculations. PMID- 26372720 TI - Guidelines for ethical behavior relating to clinical practice issues in neuromuscular and electrodiagnostic medicine. AB - The American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) developed guidelines to formalize the ethical standards that neuromuscular and electrodiagnostic (EDx) physicians should observe in their clinical and scientific activities. Neuromuscular and EDx medicine is a subspecialty of medicine that focuses on evaluation, diagnosis, and comprehensive medical management, including rehabilitation of individuals with neuromuscular disorders. Physicians working in this subspecialty focus on disorders of the motor unit, including muscle, neuromuscular junction, axon, plexus, nerve root, anterior horn cell, and the peripheral nerves (motor and sensory). The neuromuscular and EDx physician's goal is to diagnose and treat these conditions to mitigate their impact and improve the patient's quality of life. The guidelines are consistent with the Principles of Medical Ethics adopted by the American Medical Association and represent a revision of previous AANEM guidelines. PMID- 26372722 TI - Indoor dampness and mould health effects - ongoing questions on microbial exposures and allergic versus nonallergic mechanisms. PMID- 26372724 TI - Focus on Quantitative Proteomics. PMID- 26372728 TI - Prophylactic Azithromycin Therapy After Lung Transplantation: Post hoc Analysis of a Randomized Controlled Trial. AB - Prophylactic azithromycin treatment has been demonstrated to improve freedom from bronchiolitis obliterans syndrome (BOS) 2 years after lung transplantation (LTx). In the current study, we re-evaluated the long-term effects of this prophylactic approach in view of the updated classification system for chronic lung allograft dysfunction (CLAD). A retrospective, intention-to-treat analysis of a randomized controlled trial comparing prophylactic treatment with placebo (n = 43) versus azithromycin (n = 40) after LTx was performed. Graft dysfunction (CLAD), graft loss (retransplantation, mortality), evolution of pulmonary function and functional exercise capacity were analyzed 7 years after inclusion of the last study subject. Following LTx, 22/43 (51%) patients of the placebo group and 11/40 (28%) patients of the azithromycin group ever developed CLAD (p = 0.043). CLAD free survival was significantly longer in the azithromycin group (p = 0.024). No difference was present in proportion of obstructive versus restrictive CLAD between both groups. Graft loss was similar in both groups: 23/43 (53%) versus 16/40 (40%) patients (p = 0.27). Long-term pulmonary function and functional exercise capacity were significantly better in the azithromycin group (p < 0.05). Prophylactic azithromycin therapy reduces long-term CLAD prevalence and improves CLAD-free survival, pulmonary function, and functional exercise capacity after LTx. PMID- 26372729 TI - BCAT1 expression associates with ovarian cancer progression: possible implications in altered disease metabolism. AB - Previously, we have identified the branched chain amino-acid transaminase 1 (BCAT1) gene as notably hypomethylated in low-malignant potential (LMP) and high grade (HG) serous epithelial ovarian tumors, compared to normal ovarian tissues. Here we show that BCAT1 is strongly overexpressed in both LMP and HG serous epithelial ovarian tumors, which probably correlates with its hypomethylated status. Knockdown of the BCAT1 expression in epithelial ovarian cancer (EOC) cells led to sharp decrease of cell proliferation, migration and invasion and inhibited cell cycle progression. BCAT1 silencing was associated with the suppression of numerous genes and pathways known previously to be implicated in ovarian tumorigenesis, and the induction of some tumor suppressor genes (TSGs). Moreover, BCAT1 suppression resulted in downregulation of numerous genes implicated in lipid production and protein synthesis, suggesting its important role in controlling EOC metabolism. Further metabolomic analyses were indicative for significant depletion of most amino acids and different phospho- and sphingolipids following BCAT1 knockdown. Finally, BCAT1 suppression led to significantly prolonged survival time in xenograft model of advanced peritoneal EOC. Taken together, our findings provide new insights about the functional role of BCAT1 in ovarian carcinogenesis and identify this transaminase as a novel EOC biomarker and putative EOC therapeutic target. PMID- 26372731 TI - A four gene signature predicts benefit from anthracyclines: evidence from the BR9601 and MA.5 clinical trials. AB - Chromosome instability (CIN) in solid tumours results in multiple numerical and structural chromosomal aberrations and is associated with poor prognosis in multiple tumour types. Recent evidence demonstrated CEP17 duplication, a CIN marker, is a predictive marker of anthracycline benefit. An analysis of the BR9601 and MA.5 clinical trials was performed to test the role of existing CIN gene expression signatures as predictive markers of anthracycline sensitivity in breast cancer. Univariate analysis demonstrated, high CIN25 expression score was associated with improved distant relapse free survival (DRFS) (HR: 0.74, 95% CI 0.54-0.99, p = 0.046). High tumour CIN70 and CIN25 scores were associated with aggressive clinicopathological phenotype and increased sensitivity to anthracycline therapy compared to low CIN scores. However, in a prospectively planned multivariate analysis only pathological grade, nodal status and tumour size were significant predictors of outcome for CIN25/CIN70. A limited gene signature was generated, patients with low tumour CIN4 scores benefited from anthracycline treatment significantly more than those with high CIN4 scores (HR 0.37, 95% CI 0.20-0.56, p = 0.001). In multivariate analyses the treatment by marker interaction for CIN4/anthracyclines demonstrated hazard ratio of 0.35 (95% CI 0.15-0.80, p = 0.012) for DRFS. This data shows CIN4 is independent predictor of anthracycline benefit for DRFS in breast cancer. PMID- 26372730 TI - Genome-wide analysis of p53 transcriptional programs in B cells upon exposure to genotoxic stress in vivo. AB - The tumor suppressor p53 is a transcription factor that coordinates the cellular response to DNA damage. Here we provide an integrated analysis of p53 genomic occupancy and p53-dependent gene regulation in the splenic B and non-B cell compartments of mice exposed to whole-body ionizing radiation, providing insight into general principles of p53 activity in vivo. In unstressed conditions, p53 bound few genomic targets; induction of p53 by ionizing radiation increased the number of p53 bound sites, leading to highly overlapping profiles in the different cell types. Comparison of these profiles with chromatin features in unstressed B cells revealed that, upon activation, p53 localized at active promoters, distal enhancers, and a smaller set of unmarked distal regions. At promoters, recognition of the canonical p53 motif as well as binding strength were associated with p53-dependent transcriptional activation, but not repression, indicating that the latter was most likely indirect. p53-activated targets constituted the core of a cell type-independent response, superimposed onto a cell type-specific program. Core response genes included most of the known p53-regulated genes, as well as many new ones. Our data represent a unique characterization of the p53-regulated response to ionizing radiation in vivo. PMID- 26372732 TI - Distinct breast cancer stem/progenitor cell populations require either HIF1alpha or loss of PHD3 to expand under hypoxic conditions. AB - The heterogeneous nature of breast cancer is a result of intrinsic tumor complexity and also of the tumor microenvironment, which is known to be hypoxic. We found that hypoxia expands different breast stem/progenitor cell populations (cells with increased aldehyde dehydrogenase activity (Aldefluor+), high mammosphere formation capacity and CD44+CD24-/low cells) both in primary normal epithelial and tumor cells. The presence of the estrogen receptor (ER) limits hypoxia-dependent CD44+CD24-/low cell expansion.We further show that the hypoxia driven cancer stem-like cell enrichment results from a dedifferentiation process. The enhanced mammosphere formation and Aldefluor+ cell content observed in breast cancer cells relies on hypoxia-inducible factor 1alpha (HIF1alpha). In contrast, the CD44+CD24-/low population expansion is HIF1alpha independent and requires prolyl hydroxylase 3 (PHD3) downregulation, which mimics hypoxic conditions, leading to reduced CD24 expression through activation of NFkB signaling. These studies show that hypoxic conditions expand CSC populations through distinct molecular mechanisms. Thus, potential therapies that combine current treatments for breast cancer with drugs that target CSC should take into account the heterogeneity of the CSC subpopulations. PMID- 26372734 TI - Changes in microbial diversity of brined green asparagus upon treatment with high hydrostatic pressure. AB - The application of high hydrostatic pressure (HHP, 600MPa, 8 min) on brined green asparagus and the changes in bacterial diversity after treatments and during storage at 4 degrees C (30 days) or 22 degrees C (10 days) were studied. HHP treatments reduced viable cell counts by 3.6 log cycles. The residual surviving population did not increase during storage at 4 degrees C. However, bacterial counts significantly increased at 22 degrees C by day 3, leading to rapid spoilage. The microbiota of green asparagus was composed mainly by Proteobacteria (mainly Pantoea and Pseudomonas), followed by Firmicutes (mainly Lactococcus and Enterococcus) and to a less extent Bacteroidetes and Actinobacteria. During chill storage of untreated asparagus, the relative abundance of Proteobacteria as well as Enterococcus and Lactococcus decreased while Lactobacillus increased. During storage of untreated asparagus at 22 degrees C, the abundance of Bacteroidetes decreased while Proteobacteria increased during late storage. The HHP treatment determined a reduction of the Proteobacteria both early after treatment and during chill storage. In the HHP treated samples stored at 22 degrees C, the relative abundance of Pseudomonas rapidly decreased at day 1, with an increase of Bacteroidetes. This was followed by a marked increase in Enterobacteriaceae (Escherichia) simultaneously with increase in viable counts and spoilage. Results from the study indicate that the effect of HHP treatments on the viability ofmicrobial populations in foods also has an impact on the dynamics of microbial populations during the storage of the treated foods. PMID- 26372735 TI - A review of cellphone microscopy for disease detection. AB - The expansion in global cellphone network coverage coupled with advances in cellphone imaging capabilities present an opportunity for the advancement of cellphone microscopy as a low-cost alternative to conventional microscopy for disease detection in resource-limited regions. The development of cellphone microscopy has also benefitted from the availability of low-cost miniature microscope components such as low-power light-emitting diodes and ball lenses. As a result, researchers are developing hardware and software techniques that would enable such microscopes to produce high-resolution, diagnostic-quality images. This approach may lead to more widespread delivery of diagnostic services in resource-limited areas where there is a shortage of the skilled labour required for conventional microscopy and where prevalence of infectious and other diseases is still high. In this paper, we review current techniques, clinical applications and challenges faced in the field of cellphone microscopy. PMID- 26372733 TI - Expression of prokineticin-receptor2(PK-R2) is a new prognostic factor in human colorectal cancer. AB - The increased invasiveness of colorectal cancer cells is important for progression and metastasis to the surrounding organs. According to recent molecular biological studies, signaling through transmembrane Prokineticin Receptor2(PK-R2) is likely involved in the ability of tumor cell to invade. However, no studies have evaluated the relationship between PK-R2 expression, ability of cancer to invade/metastasize, and patient prognosis in cases of resected colorectal cancer. Accordingly, we have examined these factors in the present study.Immunohistochemical staining was performed to detect PK-R2 in the primary lesion and adjacent normal large intestine mucosa of 324 colorectal cancer patients who underwent resection surgery at our department. Additionally, we conducted clinicopathologic examinations and analyzed patient prognoses with the Kaplan-Meier method. Further, multivariate analysis was conducted using a cox proportional hazard model.PK-R2 expression was observed on the cellular membrane of the primary lesion in 147 of 324 cases (45.3%) of human colorectal cancer. PK R2 expression was associated with a higher incidence of vascular invasion, lymph node metastasis, hepatic metastasis, and hematogenous metastasis. Further, prevalence of PK-R2 expression increased as tumor stage increased. In stage III curative resection cases, where recurrence is the most serious problem, cases that expressed PK-R2 had a significantly lower 5-year survival rate (82.1% versus 66.8%) and higher recurrence compared to those cases with no PK-R2 expression. In the multivariate analysis for prognosis, PK-R2 expression was found to be an independent factor(ratio2.621).PK-R2 expression could be one of the new prognostic factors in human colorectal cancer. PMID- 26372738 TI - 2014 European guideline on the management of syphilis: giving evidence priority. PMID- 26372737 TI - Acylthiourea derivatives as colorimetric sensors for anions: Synthesis, characterization and spectral behaviors. AB - Several acylthioureas have been synthesized to develop colorimetric sensors for detection of biologically important anions. UV-vis titration experiments indicated that the absorbance values have a good linear relationship with concentration of anions when the anions were added in AR-1, AR-4 and AR-6 sensor molecules. The detection limit to AcO(-) and F(-) is 5*10(-6) mol/L when the concentration of receptors are 2*10(-5) mol/L. Especially, compounds AR-1 and AR 4, decorated with strong electron-withdrawing NO2 substituent, showed augmented anion sensing properties, being capable of naked-eye detecting of F(-) and AcO(-) when the water content is lower than 15%. The recognition details of anion sensing were also assessed using (1)H NMR technique and confirmed that the basic anions induced deprotonation of N-H. PMID- 26372739 TI - Radon and radioactivity at a town overlying Uranium ores in northern Greece. AB - Extensive measurements of (222)Rn in the town of Xanthi in N Greece show that the part of the town overlying granite deposits and the outcrop of a uranium ore has exceptionally high indoor radon levels, with monthly means up to 1500 Bq m(-3). A large number of houses (40%) in this part of the town exhibit radon levels above 200 Bq m(-3) while 11% of the houses had radon levels above 400 Bq m(-3). Substantial interannual variability as well as the highest in Europe winter/summer ratios (up to 12) were observed in this part of the town, which consist of traditional stone masonry buildings of the late 19th-early 20th century. Measurements of (238)U and (232)Th content of building materials from these houses as well as radionuclide measurements in different floors show that the high levels of indoor radon measured in these buildings are not due to high radon emanation rates from the building materials themselves but rather due to high radon flux from the soil because of the underlying geology, high radon penetration rates into the buildings from underground due to the lack of solid concrete foundations in these buildings, or a combination thereof. From the meteorological variables studied, highest correlation with indoor (222)Rn was found with temperature (r(2) = 0.65). An indoor radon prognostic regression model using temperature, pressure and precipitation as input was developed, that reproduced indoor radon with r(2) = 0.69. Hence, meteorology is the main driving factor of indoor radon, with temperature being the most important determinant. Preliminary flux measurements indicate that the soil-atmosphere (222)Rn flux should be in the range 150-250 Bq m(-2) h(-1), which is in the upper 10% of flux values for Europe. PMID- 26372740 TI - Canadian inter-laboratory organically bound tritium (OBT) analysis exercise. AB - Tritium emissions are one of the main concerns with regard to CANDU reactors and Canadian nuclear facilities. After the Fukushima accident, the Canadian Nuclear Regulatory Commission suggested that models used in risk assessment of Canadian nuclear facilities be firmly based on measured data. Procedures for measurement of tritium as HTO (tritiated water) are well established, but there are no standard methods and certified reference materials for measurement of organically bound tritium (OBT) in environmental samples. This paper describes and discusses an inter-laboratory comparison study in which OBT in three different dried environmental samples (fish, Swiss chard and potato) was measured to evaluate OBT analysis methods currently used by CANDU Owners Group (COG) members. The variations in the measured OBT activity concentrations between all laboratories were less than approximately 20%, with a total uncertainty between 11 and 17%. Based on the results using the dried samples, the current OBT analysis methods for combustion, distillation and counting are generally acceptable. However, a complete consensus OBT analysis methodology with respect to freeze-drying, rinsing, combustion, distillation and counting is required. Also, an exercise using low-level tritium samples (less than 100 Bq/L or 20 Bq/kg-fresh) would be useful in the near future to more fully evaluate the current OBT analysis methods. PMID- 26372741 TI - Radon-thoron discriminative measurements in the high natural radiation areas of southwestern Cameroon. AB - Although indoor radon was initially measured in the uranium regions of Poli and Lolodorf using Electret Ionization Chambers, discriminative RADUET detectors were deployed in 70 houses of the high natural radiation areas of Bikoue and Ngombas in the uranium region of Lolodorf in Southwestern Cameroon. Radon and thoron concentrations were determined using Image-J and Microscope Methods for track evaluation. Radon and thoron concentrations follow lognormal distributions and ranged respectively from 27 +/- 26 to 937 +/- 5 Bq m(-3) and from 48 +/- 40 to 700 +/- 128 Bq m(-3). The arithmetic means of radon and thoron concentrations were found to be 92 +/- 3 Bq m(-3) and 260 +/- 13 Bq m(-3.) Less than 2% of houses have indoor radon above the reference level of 300 Bq m(-3) and 30% of houses have thoron concentrations above 300 Bq m(-3.) Inhalation doses due to radon and thoron range respectively between 0.6-17.7 mSv yr(-1) and 0.2-3 mSv yr( 1) with the mean values of 1.4 mSv yr(-1) and 1 mSv yr(-1). The contribution of indoor thoron to the total inhalation dose ranges between 15%- 78.5% with the mean value of 47%. Thus thoron cannot be neglected when assessing radiation dose. PMID- 26372742 TI - Investigation into the use of cement kiln dust in high density sludge (HDS) treatment of acid mine water. AB - The purpose of this study was to investigate the potential to replace lime with cement kiln dust (CKD) in high density sludge (HDS) treatment of acid mine drainage (AMD). The bench-scale study used two water samples: AMD sampled from a lead-zinc mine with high concentrations of iron (Fe), zinc (Zn), and arsenic (As) (Fe/Zn-AMD) and a synthetic AMD solution (Syn-AMD) spiked with ferric sulfate (Fe2(SO4)3). Arsenic was found to be significantly reduced with CKD-HDS treatment of Fe/Zn-AMD compared to lime-HDS treatment, to concentrations below the stringent mine effluent discharge regulation of 0.10 mg As/L (i.e., 0.04 +/- 0.02 mg/L). Both CKD- and lime-HDS treatment of the two AMD samples resulted in settled water Fe concentrations above the stringent discharge guideline of 0.3 mg Fe/L. CKD addition in the HDS process also resulted in high settled water turbidity, above typical discharge guidelines of 15 mg TSS/L. CKD-HDS treatment was found to result in significantly improved settled solids (i.e., sludge) quality compared to that generated in the lime-HDS process. HDS treatment with CKD resulted in 25-88% lower sludge volume indices, 2 to 9 times higher % wet solids, and 10 to 20 times higher % dry solids compared to lime addition. XRD and XPS testing indicated that CKD-HDS sludge consisted of mainly CaCO3 and SiO2 with Fe(3+) precipitates attached at particle surfaces. XRD and XPS testing of the lime-HDS generated sludge showed that it consisted of non-crystalline Fe oxides typical of sludge formed from precipitates with a high water concentration. Increased sedimentation rates were also found for CKD (1.3 cm/s) compared to lime (0.3 cm/s). The increased solids loading with CKD addition compared to lime addition in the HDS process was suggested to both promote surface complexation of metal precipitates with insoluble CKD particles and increase compression effects during Type IV sedimentation. These mechanisms collectively contributed to the reduced water content of CKD-HDS sludge. The results of this study suggest that solids loading is a significant factor in increased sludge density found with the HDS process compared to conventional lime precipitation-sedimentation. PMID- 26372743 TI - Prevalence and proliferation of antibiotic resistance genes in two municipal wastewater treatment plants. AB - The propagation of antibiotic resistance genes (ARGs) is an emerging health concern worldwide. Thus, it is important to understand and mitigate their occurrence in different systems. In this study, 30 ARGs that confer resistance to tetracyclines, sulfonamides, quinolones or macrolides were detected in two activated sludge wastewater treatment plants (WWTPs) in northern China. Bacteria harboring ARGs persisted through all treatment units, and survived disinfection by chlorination in greater percentages than total Bacteria (assessed by 16S rRNA genes). Although the absolute abundances of ARGs were reduced from the raw influent to the effluent by 89.0%-99.8%, considerable ARG levels [(1.0 +/- 0.2) * 10(3) to (9.5 +/- 1.8) * 10(5) copies/mL)] were found in WWTP effluent samples. ARGs were concentrated in the waste sludge (through settling of bacteria and sludge dewatering) at (1.5 +/- 2.3) * 10(9) to (2.2 +/- 2.8) * 10(11) copies/g dry weight. Twelve ARGs (tetA, tetB, tetE, tetG, tetH, tetS, tetT, tetX, sul1, sul2, qnrB, ermC) were discharged through the dewatered sludge and plant effluent at higher rates than influent values, indicating overall proliferation of resistant bacteria. Significant antibiotic concentrations (2%-50% of raw influent concentrations) remained throughout all treatment units. This apparently contributed selective pressure for ARG replication since the relative abundance of resistant bacteria (assessed by ARG/16S rRNA gene ratios) was significantly correlated to the corresponding effluent antibiotic concentrations. Similarly, the concentrations of various heavy metals (which induce a similar bacterial resistance mechanism as antibiotics - efflux pumps) were also correlated to the enrichment of some ARGs. Thus, curtailing the release of antibiotics and heavy metals to sewage systems (or enhancing their removal in pre-treatment units) may alleviate their selective pressure and mitigate ARG proliferation in WWTPs. PMID- 26372744 TI - Need to consider full societal impact of hepatitis B virus-positive donors. PMID- 26372745 TI - First Report on the OPTN National Variance: Allocation of A2 /A2 B Deceased Donor Kidneys to Blood Group B Increases Minority Transplantation. AB - In 2002, the Organ Procurement and Transplantation Network (OPTN) Minority Affairs Committee (MAC) implemented a national, prospective, "variance of practice" to allow deceased donor, ABO blood group incompatible, A2 antigen, kidney transplantation into blood group B recipients; outcomes of this cohort were compared to ABO compatible recipients. The goal of the variance was to increase the number of transplants to B candidates without negatively impacting survival or compromising system equity. Only B recipients with low anti-A IgG titers (<1:8) were eligible to receive these kidneys. Across eight participating Donation Service Areas (DSA), there were 101 A2 /A2 B to B transplants through 12/31/11, of which the majority of the recipients (61%) were ethnic minorities. At 12, 24, and 36 months, Kaplan-Meier graft survival rates for the B recipients of A2 /A2 B kidneys were 95.0%, 90.6%, and 85.4%, respectively, comparable to outcomes for B recipients of B kidneys, 92.6%, 87.9%, and 82.5%, respectively (p value = 0.48). Five DSAs increased the proportion of B transplants during 41 months postvariance, with a lesser proportional decrease in blood group A transplants. The data support the proposition that this allocation algorithm may provide a robust mechanism to increase access of blood group B minority candidates to kidney transplantation. PMID- 26372746 TI - Cutaneous Crohn's disease successfully treated with adalimumab. PMID- 26372747 TI - CDC Will Soon Issue Guidelines for the Prevention of Surgical Site Infection. PMID- 26372748 TI - Causes and Rates of Unplanned Readmissions After Elective Primary Total Joint Arthroplasty: A Systematic Review and Meta-Analysis. AB - To address the lack of consensus on the leading reasons for readmissions after primary elective unilateral total joint arthroplasties (TJAs), we performed a systematic review and a meta-analysis to identify overall and cause-specific readmission rates. We performed structured searches of the Medline and Cochrane databases for original reports-published between January 1982 and January 2013-on both 30- and 90-day follow-ups of unique patient populations that underwent elective primary TJA. Random-effects meta-analyses were performed to obtain pooled estimates. For total hip arthroplasty (THA), the overall pooled readmission rate was 5.6% at 30 days and 7.7% at 90 days. For total knee arthroplasty (TKA), the overall rate was 3.3% at 30 days and 9.7% at 90 days. The leading reason for THA readmission was joint-specific at both 30 and 90 days, and the leading reason for TKA readmission was surgical site infection. Our systematic review and meta-analysis established baseline readmission rates in the literature on primary TJA and identified the most common reasons driving readmission for TJA. PMID- 26372750 TI - Modular Versus Nonmodular Femoral Necks for Primary Total Hip Arthroplasty. AB - In total hip arthroplasty (THA), proximal femoral neck stem modularity (PFNSM) has theoretical advantages over nonmodular stems, including the ability to more closely reconstruct anatomy and improve stability. However, risks of metallosis and breakage at the junction must be considered. In this study, we compared the head centers of a modular neck system with that of its nonmodular counterpart. Of 463 primary THAs with a modular stem, 261 (56%) had a head center equivalent to that of its nonmodular counterpart, and an additional 132 (29%) had a head center within 4 mm in length and 2 mm of offset. Thus, only 70 stems (15%) had a head center that was more than 4 mm in length and more than 2 mm in offset different from the nonmodular stem. Only 12 stems had a verted neck. These findings suggest that, in a majority of primary THAs, use of a modular stem results in head center positions also achievable with a nonmodular stem. Given the risks of modularity, PFNSM should be used with caution. We recommend PFNSM in cases that cannot be reconstructed with the nonmodular option. PMID- 26372749 TI - Radiographically Silent Loosening of the Acetabular Component in Hip Arthroplasty. AB - Polyethylene wear and subsequent osteolysis are major obstacles to the long-term success of total hip arthroplasty (THA). We conducted a study to determine the incidence of loose acetabular components that did not show frank signs of loosening on either plain radiography or computed tomography (CT), or radiographically silent loosening (RSL). In this retrospective study, we evaluated patients who underwent revision THA and were evaluated with plain radiography and CT between 2000 and 2012. Any patient with imaging that showed signs of component movement was excluded. Of the 104 patients who met the study inclusion criteria, 17 (16.3%) met the criteria for RSL of the acetabular shell. Patients with RSL presented at a similar age (P = .961) and with a similar sex profile (P = .185) compared with patients with stable acetabular components and were more likely to present with pain (P = .0487). Acetabular components may be loose even if there is no evidence of component migration on radiographic studies. Surgeons should be aware of the incidence of RSL and the potential of RSL to affect patient care and potential surgical options. PMID- 26372751 TI - Role of Surgical Dressings in Total Joint Arthroplasty: A Randomized Controlled Trial. AB - We conducted a randomized controlled trial to compare efficacy of an occlusive antimicrobial barrier dressing and a standard surgical dressing in patients who underwent primary total joint arthroplasty. Two hundred sixty-two patients were randomized to receive either an occlusive dressing or a standard dressing. Wounds were closed in identical fashion. Outcomes included wound complications, dressing changes, and patient satisfaction. With use of occlusive dressing (vs standard dressing), wound complications (including skin blistering) were significantly (P = 0.15) reduced; there were significantly (P < .0001) fewer dressing changes; and patient satisfaction was significantly (P < .0001) higher. Use of occlusive dressings can reduce wound complications and promote wound healing after total joint arthroplasty. PMID- 26372752 TI - Recorrection Osteotomies and Total Knee Arthroplasties After Failed Bilateral High Tibial Osteotomies. AB - This article reports the case of a 58-year-old man with failed bilateral opening wedge high tibial osteotomies. Because of excessive valgus deformities, each total knee arthroplasty (TKA) was combined with a recorrection osteotomy. TKAs were performed consecutively. Recorrection osteotomy using a long-stemmed tibial component and a derotation plate corrected the valgus malalignment and maintained native ligament stability in each posterior cruciate ligament-retaining TKA. PMID- 26372753 TI - Cementing Multihole, Metal, Modular Acetabular Shells Into Cages in Revision Total Hip Arthroplasty. AB - Acetabular components of total hip arthroplasties can loosen and migrate, sometimes resulting in severe osseous pelvic deficiencies that make reconstruction with standard acetabular components impossible. Reconstructive techniques used in this setting commonly involve placing a cage or ring for reconstruction. All-polyethylene acetabular components traditionally are cemented into these constructs. Disadvantages of this technique include possible recurrent dislocations, disassociation of polyethylene component from cement, and polyethylene wear. Traditional reconstructive techniques require major revision of the construct to address such problems. In this article, we describe a technique in which a multihole, metal acetabular shell is cemented into a cage or ring, permitting use of modular liners. This technique results in secure fixation to the cage and gives the surgeon the option of changing liners in cases of wear or instability. We report outcomes in 13 cases with follow-up ranging from 3 months to 133 months. Cementing a modular metal shell into a cage can be a viable alternative to cementing a polyethylene liner. This technique has resulted in durable fixation of shell to cage in our experience and permits use of variable liner options. PMID- 26372754 TI - Is Your Electronic Health Record Putting You at Risk for Documentation Audit? PMID- 26372755 TI - Perilunate Injuries. AB - Perilunate injuries often result from high-energy trauma to the carpus. Despite the severity of these injuries, they are often missed initially because of their subtle radiographic and physical examination findings. Early anatomic reduction of any carpal malalignment is paramount to a successful outcome. Even with optimal treatment, complications, such as generalized wrist stiffness, diminished grip strength, and posttraumatic arthritis, commonly develop; however, recent studies suggest these issues are often well tolerated. In this article, the basic presentation and treatment of perilunate injuries are discussed. PMID- 26372756 TI - Sustentaculum Lunatum: Appreciation of the Palmar Lunate Facet in Management of Complex Intra-Articular Fractures of the Distal Radius. AB - Fracture of the distal radius is the most common wrist injury. Treatment of complex intra-articular fractures of the distal radius requires an accurate diagnosis of the fracture pattern and a thoughtful approach to fixation. We propose a new term, sustentaculum lunatum, for the palmar lunate facet. The sustentaculum lunatum deserves specific attention because of its importance in load transmission across the radiocarpal joint. It is also key to restoring the anatomy of the palmar distal radial metaphysis during internal fixation. We provide a review of the structure and function of the sustentaculum lunatum and describe fixation techniques. This article is intended to promote awareness of this fragment in the treatment of fractures of the distal radius. PMID- 26372757 TI - Safety of Tourniquet Use in Total Knee Arthroplasty in Patients With Radiographic Evidence of Vascular Calcifications. AB - Tourniquets are often used in total knee arthroplasty (TKA) to improve visualization of structures, shorten operative time, reduce intraoperative bleeding, and improve cementing technique. Despite these advantages, controversy remains regarding the safety of tourniquet use. Tourniquets have been associated with nerve palsies, vascular injury, and muscle damage. Some have hypothesized they may also cause deep vein thrombosis. Last, increased incidence of postoperative wound complications has been reported with use of tourniquets. We conducted a retrospective cohort study to determine whether tourniquet use in TKA in patients with preexisting radiographic evidence of vascular disease increases the risk for wound complications or venous thromboembolism (VTE). Patients (N = 373) were placed in 2 groups: One had no preoperative radiographic evidence of knee arterial calcification (n = 285), and the other had arterial calcifications (n = 88). Overall, arterial calcification did not increase the risk for wound complication or VTE (P > .05). Furthermore, location of arterial calcification did not affect risk for wound complication or VTE. There were no arterial injuries. Diabetes, hypertension, prior VTE, coronary artery disease, and male sex were linked to higher wound complication rates (P < .05). Patients who have preoperative radiographic evidence of arterial calcification can safely undergo tourniquet-assisted TKA. PMID- 26372758 TI - Factors Affecting Perceptions of Open, Mini-Open, and Arthroscopic Rotator Cuff Repair Techniques Among Medical Professionals. AB - Although no long-term difference between arthroscopic and mini-open rotator cuff repairs has been documented, use of arthroscopic repair has exploded. We conducted a study to determine which repair technique medical professionals preferred for their own surgery and to analyze the perceptions shaping those opinions. A survey was emailed to selected professionals at our institution: attendings, residents, and allied health professionals; 84 (41, 20, and 23, respectively) responded. Irrespective of specialty or career length, almost half (39, 46%) preferred deferring the repair choice to their surgeon; the other 45 preferred arthroscopic (22, 26%), mini-open (19, 23%), open (2, 2%), or no (2, 2%) repair. Most agreed repairs were safe and fast but had no opinion about cost effectiveness or which technique provided the best outcome. Significantly (P < .05) more respondents thought arthroscopic and mini-open repairs promoted quick healing, good cosmetic results, and patient satisfaction compared with open repair, but these repairs were also perceived as significantly (P < .05) harder to learn and more challenging than open repair. It is important for medical professionals to recognize these biases, especially given that many defer to the judgment of their medical peers. PMID- 26372759 TI - The Role of Computed Tomography in Evaluating Intra-Articular Distal Humerus Fractures. AB - Computed tomography (CT) is often used to evaluate intra-articular distal humerus fracture patterns, but it increases radiation exposure and cost. We conducted a study to determine the effect of adding CT evaluation to plain radiographic evaluation on the classification of, and treatment plans for, intra-articular distal humerus fractures. Nine blinded orthopedic surgeons evaluated 30 consecutive fractures for classification and surgical approach. Evaluations were performed first using plain radiographs and then again using the same radiographs plus CT images. Statistical analysis was performed using the kappa correlation coefficient and Cramer V testing. We hypothesized that adding CT images to plain radiographs would change the classification and treatment of these fractures and would improve interobserver agreement on classification and treatment. Intraobserver reliability (Cramer V) was fair (.393) for classification and moderate (.426) for treatment. Interobserver reliability (Cohen kappa) did not improve with CT: For classification, kappa was .21 without CT and .20 with CT; for treatment, kappa was .28 without CT and .27 with CT. When classifying the fractures, attending surgeons chose the multiplanar fracture pattern 25.6% of the time without CT, and remained consistent at 23.3% with CT. Trainees chose this fracture pattern much less often without CT than with CT. Use of CT changed the treatment for multiplanar fractures (73.7% lateral approach vs 51.9% posterior approach with olecranon osteotomy). When added to plain radiographic evaluation, CT evaluation changes classification and treatment plans. Interobserver reliability did not improve. Less experienced surgeons were more likely to identify multiplanar fracture patterns with use of CT. We recommend performing CT for all intra-articular distal humerus fractures. PMID- 26372760 TI - Fingertip Amputation Treatment: A Survey Study. AB - Distal fingertip amputations are common injuries in work- and non-work-related accidents. There is a paucity of evidence to support use of any one treatment. We conducted a study to better understand how surgeon and patient factors influence the treatment preferences for distal fingertip amputations among a cross section of US and international hand surgeons. We sent a 16-question survey to the American Association for Hand Surgery and reciprocal international hand societies and analyzed the response data using a logistic regression model. We hypothesized that hand surgeons' treatment preferences would be varied and influenced by surgeon and patient demographics. One hundred ninety-eight hand surgeons (62% US, 38% international) responded to the survey. For each clinical scenario (Allen levels 2, 3, and 4 and volar oblique amputations), there were wide variations in treatment preferences. Wound care was less likely performed by surgeons with more than 30 years of experience or plastic surgery backgrounds. Replantation was less likely performed by US surgeons and private practice surgeons. Pedicle and homodigital flaps were more commonly performed internationally. Surgeons in practice for less than 5 years were more likely to perform skeletal shortening. For all levels and orientations of fingertip amputation queried, there is a wide range of treatment preferences. Our survey results highlight the need for a prospective randomized trial to elucidate the most effective treatments for fingertip amputations. PMID- 26372761 TI - Midterm Follow-Up of Metal-Backed Glenoid Components in Anatomical Total Shoulder Arthroplasties. AB - Loosening of the glenoid remains one of the most common complications of total shoulder arthroplasty (TSA) and is the most cited reason for performing revision arthroplasty. Ingrowth metal-backed glenoid components offer the theoretical advantage of bone growth directly into the prosthesis with a single host prosthesis interface. In the study reported here, we retrospectively reviewed the charts of patients who had TSAs performed by 2 fellowship-trained shoulder surgeons using glenoid components with porous tantalum anchors. Standard radiographs were analyzed for lucency surrounding the anchors. Before and after surgery, American Shoulder and Elbow Surgeons (ASES) scores and active forward elevation (AFE) and active external rotation (AER) measurements were recorded. Twelve shoulders (11 patients) were examined. Mean follow-up was 20 months. In all cases, radiographs showed no glenoid lucency. Mean AFE and mean AER both increased significantly (P < .01), as did postoperative ASES scores (P < .01). Porous tantalum ingrowth glenoid components show no radiographic or clinical evidence of loosening at midterm follow-up. Long-term studies are needed to determine if these midterm outcomes are maintained and provide benefit over conventional cemented polyethylene designs. PMID- 26372762 TI - Nonoperative Management of Multiple Hand Enchondromas in Ollier Disease With Progressive Ossification. AB - Ollier disease, or multiple enchondromatosis, has a distinct hallmark of disease variability and requires individualized patient treatment. This is a case report of an 18-year-old woman with Ollier disease isolated to her left hand that was treated nonoperatively for 8 years and followed with serial radiographs. Prognosis of Ollier disease limited to the bones of the hands is believed to be very good: only 12 cases of transformation to chondrosarcoma have been reported in the literature. However, a recent large retrospective multi-institutional study estimated a 15% lifetime risk of developing a malignancy at these locations. PMID- 26372763 TI - Isolated Radiopalmar Dislocation of Fifth Carpometacarpal Joint: A Rare Presentation. AB - Carpometacarpal (CMC) joint dislocations are uncommon injuries that account for less than 1% of hand injuries. Dorsal dislocations of the CMC joints are more frequent than volar dislocations. Palmar dislocations can be either ulnopalmar or radiopalmar. There are very few reports of isolated radiopalmar dislocations of the fifth CMC joint in the English-language literature. In our case of radiopalmar dislocation, diagnosis was delayed, and attempts at closed reduction were unsuccessful. Therefore, it was treated by open reduction and Kirschner-wire fixation. This article reports a rare type of injury and discusses its management. PMID- 26372764 TI - A Rare Cause of Postoperative Abdominal Pain in a Spinal Fusion Patient. AB - We present the case of a 12-year-old girl who underwent an uncomplicated posterior spinal fusion with instrumentation for scoliosis and who later developed nausea, emesis, and abdominal pain. We discuss the epidemiology, prevalence, anatomic findings, symptoms, diagnostic tests, and clinical management, including nonsurgical and surgical therapies, of superior mesenteric artery syndrome (SMAS), a rare condition. Over a 2-week period, the patient developed an uncommon type of bowel obstruction likely related to her initial thin body habitus, correction of her deformity, and weight loss after surgery. The patient returned to the operating room for placement of a Stamm gastrostomy feeding tube with insertion of a transgastric-jejunal (G-J) feeding tube. The patient had the G-J feeding tube in place for approximately 6 weeks to augment her enteral nutrition. As she gained weight, her duodenal emptying improved, and she gradually transitioned to normal oral intake. She has done well since the G-J feeding tube was removed. Posterior spinal fusion for adolescent idiopathic scoliosis is a relatively common procedure, and SMAS is a rare condition. However, in the case of an asthenic adolescent with postoperative weight loss, intestinal obstruction can develop. When planning operative spinal correction in scoliosis patients who have a low body mass index at the time of surgery and who have increased thoracic stiffness, be alert for signs and symptoms of SMAS. This rare complication can develop, and timely diagnosis and medical management will decrease morbidity and shorten the length of time needed for nutritional rehabilitation. PMID- 26372765 TI - Osteochondroma With Contiguous Bronchogenic Cyst of the Scapula. AB - Osteochondroma is a benign bone tumor composed of a bony protrusion with an overlying cartilage cap. Osteochondromas arise in the scapula in 3% to 5% of cases, making them the most common benign bone tumor in this location. Scapular osteochondromas cause various pathologies of the shoulder girdle, including snapping scapula syndrome, chest wall deformity, shoulder impingement, and bursa formation. Bronchogenic cyst is an exceedingly rare finding in the periscapular area. It is a congenital cystic mass lined by tracheobronchial structures and respiratory epithelium. To our knowledge, there are no reports of a contiguous osteochondroma and bronchogenic cyst. A 12-month-old boy presented with an incidentally noted mass on the spine of the scapula, which drained scant, clear fluid through an adjacent pinprick-sized hole. Imaging revealed an exostosis with an adjacent cystic mass. The mass and cyst were excised en bloc, and histopathologic examination confirmed the diagnosis of osteochondroma with contiguous bronchogenic cyst. In this case, we present the report of a novel dual lesion. PMID- 26372766 TI - A Picture Is Worth a Thousand Words: Unconscious Bias in the Residency Application Process? PMID- 26372767 TI - Commentary to "CDC Will Soon Issue Guidelines for the Prevention of Surgical Site Infection". PMID- 26372768 TI - Oxytocin enhances attentional bias for neutral and positive expression faces in individuals with higher autistic traits. AB - There is considerable interest in the potential therapeutic role of the neuropeptide oxytocin in altering attentional bias towards emotional social stimuli in psychiatric disorders. However, it is still unclear whether oxytocin primarily influences attention towards positive or negative valence social stimuli. Here in a double-blind, placebo controlled, between subject design experiment in 60 healthy male subjects we have used the highly sensitive dual target rapid serial visual presentation (RSVP) paradigm to investigate whether intranasal oxytocin (40IU) treatment alters attentional bias for emotional faces. Results show that oxytocin improved recognition accuracy of neutral and happy expression faces presented in the second target position (T2) during the period of reduced attentional capacity following prior presentation of a first neutral face target (T1), but had no effect on recognition of negative expression faces (angry, fearful, sad). Oxytocin also had no effect on recognition of non-social stimuli (digits) in this task. Recognition accuracy for neutral faces at T2 was negatively associated with autism spectrum quotient (ASQ) scores in the placebo group, and oxytocin's facilitatory effects were restricted to a sub-group of subjects with higher ASQ scores. Our results therefore indicate that oxytocin primarily enhances the allocation of attentional resources towards faces expressing neutral or positive emotion and does not influence that towards negative emotion ones or non-social stimuli. This effect of oxytocin is strongest in healthy individuals with higher autistic trait scores, thereby providing further support for its potential therapeutic use in autism spectrum disorder. PMID- 26372769 TI - A novel locus in the oxidative stress-related gene ALOX12 moderates the association between PTSD and thickness of the prefrontal cortex. AB - Oxidative stress has been implicated in many common age-related diseases and is hypothesized to play a role in posttraumatic stress disorder (PTSD)-related neurodegeneration (Miller and Sadeh, 2014). This study examined the influence of the oxidative stress-related genes ALOX 12 and ALOX 15 on the association between PTSD and cortical thickness. Factor analyses were used to identify and compare alternative models of the structure of cortical thickness in a sample of 218 veterans. The best-fitting model was then used for a genetic association analysis in White non-Hispanic participants (n=146) that examined relationships between 33 single nucleotide polymorphisms (SNPs) spanning the two genes, 8 cortical thickness factors, and each SNP*PTSD interaction. Results identified a novel ALOX12 locus (indicated by two SNPs in perfect linkage disequilibrium: rs1042357 and rs10852889) that moderated the association between PTSD and reduced thickness of the right prefrontal cortex. A whole-cortex vertex-wise analysis showed this effect to be localized to clusters spanning the rostral middle frontal gyrus, superior frontal gyrus, rostral anterior cingulate cortex, and medial orbitofrontal cortex. These findings illustrate a novel factor-analytic approach to neuroimaging-genetic analyses and provide new evidence for the possible involvement of oxidative stress in PTSD-related neurodegeneration. PMID- 26372771 TI - Severe neurotrauma in Switzerland: have short-term outcomes improved? AB - Neurotrauma has a high incidence in high-income countries (790 per 100,000 population per year) and can be considered a silent epidemic. Severe traumatic brain injury (TBI) is a major burden for societies and is associated with high costs for both immediate and long-term care. Population-based studies including patients with severe TBI are rare. A recent cohort study in Switzerland observed an incidence of 11 / 100,000 population / year. Mortality rate at 14 days post injury was 30% in Switzerland and was associated with the severity of the injury and the age of the injured person. Thirty-five percent of patients were >65 years; in this subpopulation the incidence (22/100,000/year) and death rate (41%) were higher; this high proportion of elderly patients in this setting is new. A decrease in disability in the first year after TBI was observed in large multicentre cohort studies including the Swiss cohort study. There is some evidence that the speed of decrease of disability over time is associated with intensive neurorehabilitation. In conclusion, short-term outcome may have improved for younger patients over recent years, but this improvement may be masked by the higher proportion of elderly patients with less favourable outcomes. Additionally, we propose that clinical pathways from the prehospital period to rehabilitation could be improved, and in turn allow a higher level of positive outcomes not only in young but also in elderly patients. PMID- 26372770 TI - Prenatal stress, development, health and disease risk: A psychobiological perspective-2015 Curt Richter Award Paper. AB - The long-term consequences of exposure to excess stress, particularly during sensitive developmental windows, on the initiation and progression of many complex, common physical and mental disorders that confer a major global burden of disease are well established. The period of intrauterine life represents among the most sensitive of these windows, at which time the effects of stress may be transmitted inter-generationally from a mother to her as-yet-unborn child. As explicated by the concept of fetal or developmental programming of health and disease susceptibility, a growing body of evidence supports the notion that health and disease susceptibility is determined by the dynamic interplay between genetic makeup and environment, particularly during intrauterine and early postnatal life. Except in extreme cases, an adverse intrauterine exposure may not, per se, 'cause' disease, but, instead, may determine propensity for disease(s) in later life (by shaping phenotypic responsivity to endogenous and exogenous disease-related risk conditions). Accumulating evidence suggests that maternal psychological and social stress during pregnancy represents one such condition that may adversely affect the developing child, with important implications for a diverse range of physical and mental health outcomes. In this paper we review primarily our own contributions to the field of maternal stress during pregnancy and child mental and physical health-related outcomes. We present findings on stress-related maternal-placental-fetal endocrine and immune/inflammatory processes that may mediate the effects of various adverse conditions during pregnancy on the developing human embryo and fetus. We enunciate conceptual and methodological issues related to the assessment of stress during pregnancy and discuss potential mechanisms of intergenerational transmission of the effects of stress. Lastly, we describe on-going research and some future directions of our program. PMID- 26372772 TI - History and Development of Tsuchiya General Hospital in Hiroshima. PMID- 26372773 TI - Retraction Statement. Paper by Bener A, Alsaied A, Al-Ali M, Hassan AS, Basha B, Al-Kubaisi A, Abraham A, Mian M, Guiter G and Tewfik I, entitled 'Impact of lifestyle and dietary habits on hypovitaminosis D in type 1 diabetes mellitus and healthy children from Qatar, a sun-rich country' Ann Nutr Metab2008;53:215-222, DOI: 10.1159/000184439. PMID- 26372774 TI - Postoperative Outcome after Major Liver Resection in Jaundiced Patients with Proximal Bile Duct Cancer without Preoperative Biliary Drainage. AB - BACKGROUND/AIMS: The need for routine use of preoperative biliary drainage (PBD) before major liver resection in jaundiced patients has recently been questioned. Our aim was to present our experience of patients with proximal bile duct cancer who undergo major liver resection without PBD and compare these results with patients without biliary obstruction who underwent major liver resection. METHODS: Eighty six consecutive jaundiced patients underwent major liver resection without PBD. The postoperative outcome was compared to the control group, which was the same size and matched. DESIGN: A case-comparison study. RESULTS: Fifty nine jaundiced patients (69%) and 22 non-jaundiced patients (25%) received blood transfusion (p = 0.04). Fifty-three patients (62%) in the jaundiced group and 17 (19%) in the non-jaundiced patients experienced postoperative complications (p = 0.003). A statistically significant difference could not be detected for mortality (6 vs. 2%) and transient liver failure (10 vs. 3%). Those patients who underwent extended right hemihepatectomy (with future liver remnant <50%) express high morbidity (55 vs. 24%; p = 0.04) and mortality (23 vs. 8%; p = 0.001) compared to the non-jaundiced patients. CONCLUSIONS: Major liver resection without PBD leaving a liver remnant of more than 50% is safe in jaundiced patients. However, transfusion requirement and morbidity are higher in jaundiced patients than in non-jaundiced patients. PMID- 26372775 TI - Sulforaphane Alone and in Combination with Clofarabine Epigenetically Regulates the Expression of DNA Methylation-Silenced Tumour Suppressor Genes in Human Breast Cancer Cells. AB - BACKGROUND/AIM: Sporadic breast cancer is frequently associated with aberrant DNA methylation patterns that are reversible and responsive to environmental factors, including diet. In the present study, we investigated the effects of sulforaphane (SFN), a phytochemical from cruciferous vegetables, on the methylation and expression of PTEN and RARbeta2 tumour suppressor genes as well as on the expression of regulators of DNA methylation reaction, DNMT1 , p53 , and p21 , in MCF-7 and MDA-MB-231 human breast cancer cells with different invasive potential. We also evaluate the role of SFN epigenetic effects in support of therapy with clofarabine (ClF) that was recently shown to modulate the epigenome as well. METHODS: Promoter methylation and gene expression were estimated using methylation-sensitive restriction analysis and real-time PCR, respectively. RESULTS: In both MCF-7 and MDA-MB-231 cells, SFN at IC 50 (22 and 46 MU M , respectively) and a physiologically relevant 10 MU M concentration lead to hypomethylation of PTEN and RARbeta2 promoters with concomitant gene upregulation. The combination of SFN and ClF enhances these effects, resulting in an increase in cell growth arrest and apoptosis at a non-invasive breast cancer stage. CONCLUSIONS: Our findings provide evidence that SFN activates DNA methylation-silenced tumour suppressor genes in breast cancer cells and may contribute to SFN-mediated support of therapy with an anti-cancer drug, ClF, increasing its applications in solid tumours. PMID- 26372776 TI - The Need for Resistance Surveillance and Antimicrobial Susceptibility Testing of Helicobacter pylori. PMID- 26372777 TI - Micropatterned Azopolymer Surfaces Modulate Cell Mechanics and Cytoskeleton Structure. AB - Physical and chemical characteristics of materials are important regulators of cell behavior. In particular, cell elasticity is a fundamental parameter that reflects the state of a cell. Surface topography finely modulates cell fate and function via adhesion mediated signaling and cytoskeleton generated forces. However, how topographies alter cell mechanics is still unclear. In this work we have analyzed the mechanical properties of peripheral and nuclear regions of NIH 3T3 cells on azopolymer substrates with different topographic patterns. Micrometer scale patterns in the form of parallel ridges or square lattices of surface elevations were encoded on light responsive azopolymer films by means of contactless optical methods. Cell mechanics was investigated by atomic force microscopy (AFM). Cells and consequently the cell cytoskeleton were oriented along the linear patterns affecting cytoskeletal structures, e.g., formation of actin stress fibers. Our data demonstrate that topographic substrate patterns are recognized by cells and mechanical information is transferred by the cytoskeleton. Furthermore, cytoskeleton generated forces deform the nucleus, changing its morphology that appears to be related to different mechanical properties in the nuclear region. PMID- 26372778 TI - Cucurbit[8]uril as nanocontainer in a polyelectrolyte multilayer film: a quantitative and kinetic study of guest uptake. AB - The host-guest chemistry of cucurbit[8]uril (CB[8]) and the layer-by-layer self assembly technique are combined to obtain a molecular imprinted polyelectrolyte multilayer film for the recognition and binding of a guest molecule. Cucurbit[8]uril as a ready-made binding site is first associated with a polyelectrolyte and then assembled into a polyelectrolyte multilayer film via layer-by-layer deposition. A cationic guest is subsequently included into the nanocontainer due to specific host-guest interactions. The quantitative analysis of both CB[8] and the included guest molecule in dependence of the surface charge of the multilayer film identifies a high nanocontainer density as well as good to excellent binding efficiencies, therefore yielding a promising imprinted nanomaterial with potential applications in filtration or sensor technology. The investigation of the guest molecule uptake kinetics reveals two processes on different time scales, respectively, which are again related to the charge of the multilayer film surface. The combination of the results obtained from both ultraviolet spectroscopy and dissipative quartz crystal microbalance enables us to describe a full picture of several simultaneous processes initiated by the guest molecule. PMID- 26372780 TI - Sequential Oxidative alpha-Cyanation/Anti-Markovnikov Hydroalkoxylation of Allylamines. AB - Iron-catalyzed oxidative alpha-cyanations at tertiary allylamines in the allylic position are followed by anti-Markovnikov additions of alcohols across the vinylic CC double bonds of the initially generated alpha-amino nitriles. These consecutive reactions generate 2-amino-4-alkoxybutanenitriles from three reactants (allylamines, trimethylsilyl cyanide, and alcohols) in one reaction vessel at ambient temperature. PMID- 26372779 TI - Rising Billing for Intermediate Intensive Care among Hospitalized Medicare Beneficiaries between 1996 and 2010. AB - RATIONALE: Intermediate care (i.e., step-down or progressive care) is an alternative to the intensive care unit (ICU) for patients with moderate severity of illness. The adoption and current use of intermediate care is unknown. OBJECTIVES: To characterize trends in intermediate care use among U.S. hospitals. METHODS: We examined 135 million acute care hospitalizations among elderly individuals (>=65 yr) enrolled in fee-for-service Medicare (U.S. federal health insurance program) from 1996 to 2010. We identified patients receiving intermediate care as those with intensive care or coronary care room and board charges labeled intermediate ICU. MEASUREMENTS AND MAIN RESULTS: In 1996, a total of 960 of the 3,425 hospitals providing critical care billed for intermediate care (28%), and this increased to 1,643 of 2,783 hospitals (59%) in 2010 (P < 0.01). Only 8.2% of Medicare hospitalizations in 1996 were billed for intermediate care, but billing steadily increased to 22.8% by 2010 (P < 0.01), whereas the percentage billed for ICU care and ward-only care declined. Patients billed for intermediate care had more acute organ failures diagnoses codes compared with general ward patients (22.4% vs. 15.8%). When compared with patients billed for ICU care, those billed for intermediate care had fewer organ failures (22.4% vs. 43.4%), less mechanical ventilation (0.9% vs. 16.7%), lower mean Medicare spending ($8,514 vs. $18,150), and lower 30-day mortality (5.6% vs. 16.5%) (P < 0.01 for all comparisons). CONCLUSIONS: Intermediate care billing increased markedly between 1996 and 2010. These findings highlight the need to better define the value, specific practices, and effective use of intermediate care for patients and hospitals. PMID- 26372781 TI - What Determines the Location of a Small Solute in a Nanoconfined Liquid? AB - Replica exchange molecular dynamics simulations are used to investigate the position-dependent densities of three small molecules dissolved in acetonitrile confined in nanoscale hydrophilic silica pores. The solutes, methanol, acetone, and carbon dioxide, differ in polarity and hydrogen-bonding properties. All three molecules are found preferentially near the pore interface at room temperature, but the surface affinity differs with the solute interactions. Methanol, in particular, exists in two distinct conformations that differ in the hydrogen bonding state. Free energy profiles as a function of distance from the pore surface are decomposed into internal energy and entropic contributions. These reveal that entropy as well as hydrogen bonding can play important roles in determining the solute location and orientation. These and other relevant factors are examined to elucidate the origins of the solute density profiles within the pore. PMID- 26372782 TI - [New Imaging Technologies for the Retina]. PMID- 26372783 TI - [News in Retinal Imaging]. AB - New developments in retinal imaging have revolutionised ophthalmology in recent years. In particular, optical coherence tomography (OCT) provides highly resolved and well reproducible images and has rung in a new era in ophthalmological imaging. The technology was introduced in the early 1990 s, and has rapidly developed. There have been improvements in resolution, sensitivity and processing speed. There have also been developments in functional processing. OCT angiography is the first application in routine clinical work. PMID- 26372784 TI - [Anatomic Success of Pars Plana Vitrectomy for Rhegmatogenous Retinal Detachment during the Changeover from 20 to 23 Gauge - A Study on 313 Consecutive Cases]. AB - BACKGROUND: The aim of this investigation was to evaluate the effect on the anatomic surgical success with the changeover from 20 Gauge (G) (n = 206) to 23 G (n = 107) pars plana vitrectomy (PPV) in rhegmatogenous retinal detachment. METHODS: 313 consecutive patients were retrolective-prospectively analysed. Several parameters including lens status, number of retinal breaks, extent of retinal detachment, proliferative vitreoretinopathy (PVR) and refractive error were examined. Primary success rate was defined as anatomic success after a minimum follow-up of 6 months. The secondary success rate was determined as anatomic success after one further operation if necessary. Moreover recurring retinal detachment after initial success was registered. In additional to the analysis over all patients, cases were grouped according to the severity of the preoperative baseline situation. RESULTS: Primary success rate was 87.4 % for 20 G PPV and 87.9 % for 23 G PPV, secondary success rate was 95.6 % for 20 G PPV and 94.4 % for 23 G PPV. 13.9 % (20 G) and 7.4 % (23 G) of patients with initially reattached retina after one surgery developed recurrent retinal detachment in the follow-up and were successfully treated in 17/25 and 7/7 cases. With 20 G PPV a primary success rate of 85 % was obtained in phakic eyes and 89.6 % in pseudophakic eyes, respectively. However, primary success rate with 23 G PPV was 90.4 % for phakic eyes and 85.5 % for pseudophakic eyes. For simple, medium and severe cases, the primary success rate decreased from 97.1 to 92.4 and 74.2 % in 20 G PPV, whereas no obvious tendency appeared for 23 G PPV (93.9, 83.7, 88 %). In 20 G PPV surgery the lens status had no influence on the primary success rate (p > 0.05), for medium and severe cases in 23 G PPV better results were obtained in phakic eyes (88.5 and 93.3 %) compared to pseudophakic eyes (78.3 and 80 %, n. s.). CONCLUSION: 20 G PPV as well as 23 G PPV are good surgical techniques in rhegmatogenous retinal detachment. Overall the miniaturisation of surgical instruments seems to be without any disadvantage for the surgical success. PMID- 26372785 TI - [Why Did Adam Elsheimer Paint the Moon Upside-Down? Telescopic Vision Is Possible Without a Telescope]. PMID- 26372786 TI - [Not Available]. PMID- 26372787 TI - Terahertz Quantum Plasmonics of Nanoslot Antennas in Nonlinear Regime. AB - Quantum tunneling in plasmonic nanostructures has presented an interesting aspect of incorporating quantum mechanics into classical optics. However, the study has been limited to the subnanometer gap regime. Here, we newly extend quantum plasmonics to gap widths well over 1 nm by taking advantage of the low-frequency terahertz regime. Enhanced electric fields of up to 5 V/nm induce tunneling of electrons in different arrays of ring-shaped nanoslot antennas of gap widths from 1.5 to 10 nm, which lead to a significant nonlinear transmission decrease. These observations are consistent with theoretical calculations considering terahertz funneling-induced electron tunneling across the gap. PMID- 26372788 TI - Maternal mental health and risk of child protection involvement: mental health diagnoses associated with increased risk. AB - BACKGROUND: Previous research shows that maternal mental illness is an important risk factor for child maltreatment. This study aims to quantify the relationship between maternal mental health and risk of child maltreatment according to the different types of mental health diagnoses. METHODS: The study used a retrospective cohort of children born in Western Australia between 1990 and 2005, with deidentified linked data from routine health and child protection collections. RESULTS: Nearly 1 in 10 children (9.2%) of mothers with a prior mental health contact had a maltreatment allegation. Alternatively, almost half the children with a maltreatment allegation had a mother with a mental health contact. After adjusting for other risk factors, a history of mental health contacts was associated with a more than doubled risk of allegations (HR=2.64, 95% CI 2.50 to 2.80). Overall, all mental health diagnostic groups were associated with an increased risk of allegations. The greatest risk was found for maternal intellectual disability, followed by disorders of childhood and psychological development, personality disorders, substance-related disorders, and organic disorders. Maltreatment allegations were substantiated at a slightly higher rate than for the general population. CONCLUSIONS: Our study shows that maternal mental health is an important factor in child protection involvement. The level of risk varies across diagnostic groups. It is important that mothers with mental health issues are offered appropriate support and services. Adult mental health services should also be aware and discuss the impact of maternal mental health on the family and children's safety and well-being. PMID- 26372789 TI - Liver enzymes and incident diabetes in China: a prospective analysis of 10 764 participants in the Guangzhou Biobank Cohort Study. PMID- 26372790 TI - The 2014-2015 Ebola saga: lessons for the future. PMID- 26372791 TI - Relative severity of fumonisin contamination of cereal crops in West Africa. AB - Traditional and improved varieties of maize, pearl millet and sorghum were planted by small-scale farmers under the direction of the International Institute for Tropical Agriculture in two Nigerian agro-ecological zones: the Sudan Savanna and the Northern Guinea Savanna. Samples were collected for the determination of Fusarium infection and fumonisin (B1, B2 and B3) contamination. A previous paper reported Aspergillus infection and aflatoxin contamination of these samples. Fusarium infection levels, measured by per cent kernels infected, were modest with mean levels for the above cereals of 16% +/- 11% (SD), 12% +/- 7% and 13% +/ 16%, respectively. However, the Fusarium species recovered from maize were predominantly the fumonisin producers F. verticillioides and F. proliferatum, together making an infection rate of 15% +/- 10%, whereas these species were present to a limited extent only in the other two cereals, 1% +/- 1% for pearl millet and 2% +/- 6% for sorghum. Fumonisin contamination was variable but reflected the diversity of Fusarium producers in these three cereals. Mean levels were 228 +/- 579 ug kg(-1) (range < 5-2860 ug kg(-1)) for maize, 18 +/- 7 ug kg( 1) (range = 6-29 ug kg(-1)) for pearl millet and 131 +/- 270 ug kg(-1) (range < 5 1340 ug kg(-1)) for sorghum. Together with previous results on aflatoxin, this study confirmed the co-occurrence of aflatoxins and fumonisins in maize as well as in the traditional African cereals, millet and sorghum (89% co-occurrence across all three cereals). The low fumonisin levels may be ascribed to the use of good agricultural practices. Of the Fusarium species present, those in maize consisted mainly of fumonisin producers, the opposite of what was observed in pearl millet and sorghum. It is concluded that replacement of maize by pearl millet and sorghum could improve food safety with regards to aflatoxin B and fumonisin B exposure. PMID- 26372792 TI - The role of quantitative safety evaluation in regulatory decision making of drugs. AB - Evaluation of safety is a critical component of drug review at the US Food and Drug Administration (FDA). Statisticians are playing an increasingly visible role in quantitative safety evaluation and regulatory decision-making. This article reviews the history and the recent events relating to quantitative drug safety evaluation at the FDA. The article then focuses on five active areas of quantitative drug safety evaluation and the role Division of Biometrics VII (DBVII) plays in these areas, namely meta-analysis for safety evaluation, large safety outcome trials, post-marketing requirements (PMRs), the Sentinel Initiative, and the evaluation of risk from extended/long-acting opioids. This article will focus chiefly on developments related to quantitative drug safety evaluation and not on the many additional developments in drug safety in general. PMID- 26372793 TI - Congenital prosopagnosia in a child: Neuropsychological assessment, eye movement recordings and training. AB - Here we report the assessment and treatment of a 6-year-old boy (L.G.) who was referred to us for congenital prosopagnosia (CP). We investigated his performance using a test battery and eye movement recordings pre- and post-training. L.G. showed deficits in recognising relatives and learning new faces, and misrecognition of unfamiliar people. Eye movement recordings showed that L.G. focused on the lower part of stimuli in naming tasks based on familiar or unfamiliar incomplete or complete faces. The training focused on improving his ability to explore internal features of faces, to discriminate specific facial features of familiar and unfamiliar faces, and to provide his family with strategies to use in the future. At the end of the training programme L.G. no longer failed to recognise close and distant relatives and classmates and did not falsely recognise unknown people. PMID- 26372794 TI - Advances in the treatment options for vitiligo: activated low-dose cytokines based therapy. AB - INTRODUCTION: Vitiligo is a skin disorder characterized by a progressive depigmentation, which is caused by the loss of melanocytes at the cutaneous level. A shift of the immune system with a prevalence of T helper (Th)1/Th17 response instead of a Tregs/Th2 one and may be part of etiology of 10 vitiligo. AREAS COVERED: This review describes the major points of vitiligo onset and shows the cutting-edge results in the field of low-dose medicine in the treatment of dermatologic diseases and, in particular. in vitiligo. In this review on advances in vitiligo pharmacotherapy, the most pertinent recent publications are reported. Electronic databases such as PubMed were searched for terms 'low-dose medicine' or 'low dose and vitiligo' or 'low dose and psoriasis.' EXPERT OPINION: The availability of a systemic treatment for vitiligo, based on the oral administration of low-dose activated signaling molecules represents an opportunity for the dermatologists to overcome some specific pitfalls of currently available therapeutic protocols. PMID- 26372795 TI - Analogs, formulations and derivatives of imatinib: a patent review. AB - INTRODUCTION: The Bcr-Abl inhibitor imatinib was approved in 2001 for chronic myeloid leukemia therapy, and dramatically changed the lives of patients affected by this disease. Since it also inhibits platelet derived growth factor receptor (PDGFR) and c-Kit, imatinib is used for various other tumors caused by abnormalities of one or both these two enzymes. AREAS COVERED: This review presents an overview on imatinib formulations and derivatives, synthetic methodologies and therapeutic uses that have appeared in the patent literature since 2008. EXPERT OPINION: Innovative imatinib formulations, such as nanoparticles containing the drug, will improve its bioavailability. Moreover, oral solutions or high imatinib content tablets or capsules will improve patient compliance. Some solid formulations and innovative syntheses that have appeared in the last few years will reduce the cost of the drug, offering big advantages for poor countries. Some recently patented efficacious imatinib derivatives are in preclinical studies and could enter clinical trials in the next few years. Overall, Bcr-Abl inhibitors constitute a very appealing research field that can be expected to expand further. PMID- 26372796 TI - MicroRNAs in cancer therapeutics: "from the bench to the bedside". AB - MicroRNAs (miRNAs) are non-coding RNA transcripts that regulate physiological processes by targeting proteins directly. Their involvement in research has been robust, and evidence of their regulative functions has granted them the title: master regulators of the human genome. In cancer, they are considered important therapeutic agents, due to the fact that their aberrant expression contributes to disease development, progression, metastasis, therapeutic response and patient overall survival. This has endeavored fields of biomedical sciences to invest in developing and exploiting miRNA-based therapeutics thoroughly. Herein we highlight relevant ongoing/open clinical trials involving miRNAs and cancer. PMID- 26372799 TI - Risks May Not Be Reasons for COPD Readmissions. PMID- 26372797 TI - Update on reslizumab for eosinophilic asthma. AB - INTRODUCTION: Patients with severe eosinophilic asthma have an unmet need for novel and efficacious treatments. Reslizumab is one of the three monoclonal antibodies targeting the IL-5 pathway and has been found in Phase IIIb clinical trials to reduce asthma exacerbations, control asthma-related symptoms and improve pulmonary function in patients with eosinophilic asthma. AREAS COVERED: In this article, we discuss the results of asthma clinical trials using reslizumab, beginning with a discussion of the relationship between eosinophils, IL-5 and asthma. We conducted PubMed searches using the terms 'reslizumab', 'anti IL-5', 'eosinophilic asthma', 'IL-5 asthma'. We also searched ClinicalTrials.gov for 'reslizumab', 'reslizumab asthma', 'SCH 55700', 'SCH 55700 asthma', 'Cinquil' and 'Cinquil asthma'. EXPERT OPINION: Reslizumab and other anti-IL-5 therapies have seen success in recent trials through more stringent study participant selection targeting eosinophilic inflammation. This selection can now be based on simple blood counts. These drugs have shown a very good safety profile, but long term safety data are not yet available. Approval for these drugs is eagerly awaited by clinicians and patients alike. PMID- 26372800 TI - Timing of ARDS Onset. A Neglected Confounder. PMID- 26372801 TI - EBUS-TBNA for the Diagnosis of Lymphoma. Still an Achilles Heel. PMID- 26372802 TI - Interventional Bronchoscopy in 2015. Removing Endoluminal and Methodological Obstructions. PMID- 26372803 TI - Developing Sleep Medicine Internationally. PMID- 26372805 TI - Enigmatic Fever and Delirium in a Critically Ill Patient. PMID- 26372806 TI - First Exposure to Continuous Positive Airway Pressure Therapy for a Patient with Symptoms Suggestive of Severe Obstructive Sleep Apnea. PMID- 26372804 TI - ATS Core Curriculum 2015. Part I: Adult Pulmonary Medicine. PMID- 26372807 TI - Spontaneous Regression of Malignant Pleural Mesothelioma in a Patient with New Onset Inflammatory Arthropathy. PMID- 26372808 TI - Potential Association between Thoracic Empyema and Collateral Bronchial Arteries in Chronic Thromboembolic Pulmonary Hypertension. PMID- 26372809 TI - Sleep-Disordered Breathing in Patients with Chronic Obstructive Pulmonary Disease. PMID- 26372810 TI - Reply: Sleep-Disordered Breathing in Patients with Chronic Obstructive Pulmonary Disease. PMID- 26372811 TI - Resected pancreatic ductal adenocarcinomas with recurrence limited in lung have a significantly better prognosis than those with other recurrence patterns. AB - The majority of patients with curative resection of pancreatic ductal adenocarcinoma recur within 5 years of resection. However, the prognosis associated with different patterns of recurrence has not been well studied. A retrospective review of patients who underwent curative surgical resection of pancreatic cancer was performed. Of the 209 patients, 174 patients developed recurrent disease. Of these 174, 28(16.1%) had recurrent disease limited to lung metastases, 20(11.5%) had recurrence in the lung plus one or more other sites excluding the liver, 73(42.0%) had liver metastasis alone or liver metastasis with any other site except lung, 28(16.1%) local recurrence only, and 25(14.3%) peritoneal recurrence alone or together with local recurrence. Patients with recurrence limited to lung had a 8.5 months(Mo) median survival from recurrence to death, which was significantly better than the survival associated with recurrence in the liver(5.1Mo), in the peritoneum(2.3Mo) or locally(5.1Mo) in multivariable analyses. Among all groups, the time from surgery to the diagnosis of recurrence in patients who recurred in only in the lung was also the longest. However, 75% of patients were found to have indeterminate lung nodules on their surveillance CT scans prior to the diagnosis of recurrence in lung. This delayed diagnosis of lung recurrence may have a negative impact on survival after recurrence. In conclusion, pancreatic cancer with lung recurrence has a significantly better prognosis than recurrence in other sites. Further studies are needed to investigate how different diagnostic and treatment modalities affect the survival of this unique subpopulation of pancreatic cancer patients. PMID- 26372812 TI - Self-assembling nanoparticles encapsulating zoledronic acid revert multidrug resistance in cancer cells. AB - The overexpression of ATP binding cassette (ABC) transporters makes tumor cells simultaneously resistant to several cytotoxic drugs. Impairing the energy metabolism of multidrug resistant (MDR) cells is a promising chemosensitizing strategy, but many metabolic modifiers are too toxic in vivo. We previously observed that the aminobisphosphonate zoledronic acid inhibits the activity of hypoxia inducible factor-1a (HIF-1a), a master regulator of cancer cell metabolism. Free zoledronic acid, however, reaches low intratumor concentration. We synthesized nanoparticle formulations of the aminobisphosphonate that allow a higher intratumor delivery of the drug. We investigated whether they are effective metabolic modifiers and chemosensitizing agents against human MDR cancer cells in vitro and in vivo. At not toxic dosage, nanoparticles carrying zoledronic acid chemosensitized MDR cells to a broad spectrum of cytotoxic drugs, independently of the type of ABC transporters expressed. The nanoparticles inhibited the isoprenoid synthesis and the Ras/ERK1/2-driven activation of HIF 1alpha, decreased the transcription and activity of glycolytic enzymes, the glucose flux through the glycolysis and tricarboxylic acid cycle, the electron flux through the mitochondrial respiratory chain, the synthesis of ATP. So doing, they lowered the ATP-dependent activity of ABC transporters, increasing the chemotherapy efficacy in vitro and in vivo. These effects were more pronounced in MDR cells than in chemosensitive ones and were due to the inhibition of farnesyl pyrophosphate synthase (FPPS), as demonstrated in FPPS-silenced tumors. Our work proposes nanoparticle formulations of zoledronic acid as the first not toxic metabolic modifiers, effective against MDR tumors. PMID- 26372813 TI - Genetic variations in the TERT and CLPTM1L gene region and gastrointestinal stromal tumors risk. AB - Recent studies have suggested polymorphisms in the TERT and CLPTM1L region are associated with carcinogenesis of many distinct cancer types, including gastrointestinal cancers. However, the contribution of polymorphisms in the TERT and CLPTM1L gene region to gastrointestinal stromal tumors (GISTs) risk is still unknown. We tested the six tagSNPs on TERT and CLPTM1L region with GIST risk, using a population-based, two-stage, case-control study in 2,000 subjects. Functional validation was conducted to validate our findings of TERT rs2736098 and explore its influence on relative telomere length (RTL) in GIST cells. It showed that variant rs2736098 was significantly associated with increased risk of GIST (per allele OR = 1.29, 95% CI: 1.14-1.47, P = 7.03 * 10-5). The difference remain significant after Bonferroni correction (P = 7.03 * 10-5 * 6 = 4.2 * 10 4). Real-time PCR showed carriers of genotype CC have the longest RTL, following by carriers of genotype CT, while carriers of genotype TT have the shortest RTL in GIST tissues (P < 0.001). Our data provide evidence to implicate TERT rs2736098 polymorphism as a novel susceptibility factor for GIST risk. PMID- 26372816 TI - Locked-in-like fulminant infantile Guillain-Barre syndrome associated with herpes simplex virus 1 infection. AB - INTRODUCTION: Guillain-Barre syndrome (GBS) may rarely manifest as a peripheral locked-in syndrome. METHODS: Clinical and instrumental features of a fulminant form of infantile GBS were assessed. RESULTS: After 2 days of rhinitis, a 6-month old infant was intubated in the emergency room for sudden-onset respiratory failure. Neurological examination showed generalized areflexic flaccid paralysis with no detectable interaction, which resembled a coma. Brain MRI was normal. Lumbar puncture showed pleocytosis (43 cells/mm(3)) and herpes simplex virus 1 (HSV1) PCR positivity. EEG showed normal sleep-wake cycles, and EMG demonstrated nerve inexcitability. Acyclovir and immunoglobulins provided no benefit. After 1 week, lumbar puncture showed albuminocytological dissociation (protein 217 mg/dl). Plasmapheresis was then started, and progressive improvement occurred. At age 1 year, the child had recovered well with residual distal lower limb hyporeflexic weakness. CONCLUSIONS: A fulminant infantile GBS variant presenting as peripheral locked-in syndrome can be associated with HSV1 infection likely due to autoimmune cross-reactivity. PMID- 26372817 TI - Validation of the Besta Neurological Institute rating scale for myasthenia gravis. AB - INTRODUCTION: We validated the scale for myasthenia gravis (MG) developed at the Neurological Institute Foundation of Milan (INCB-MG scale). METHODS: A total of 174 patients were evaluated with the INCB-MG and compared with the MG Composite (MGC) as the gold standard. Dimensionality, reliability, and validity of the INCB MG scale were studied by principal component factor analysis, Cronbach alpha, and Pearson correlation coefficients; interobserver reliability was calculated by the weighted Cohen K coefficient. RESULTS: Generalized and bulbar INCB-MG subscales were unidimensional with excellent consistency; the INCB-MG and MGC scales were strongly correlated. Fatigability assessment was correlated with the INCB-MG generalized, bulbar, and respiratory subscales. CONCLUSIONS: The INCB-MG scale is a reliable tool to assess MG and is strongly correlated with the MGC. The INCB-MG scale is a valid tool for every day practice and should be further investigated for its application in clinical trials. PMID- 26372815 TI - Piperlongumine for Enhancing Oral Bioavailability and Cytotoxicity of Docetaxel in Triple-Negative Breast Cancer. AB - Very low oral bioavailability due to extensive pre-systemic metabolism and P-gp efflux has constrained the oral metronomic chemotherapy of docetaxel (DTX). There is tremendous need of compounds facilitating oral delivery of DTX. The research was aimed to investigate the effect of piperlongumine (PPL) on human liver microsomal metabolism, Caco-2 permeability, and cytotoxicity of DTX in triple negative breast cancer cell lines. Reduction in testosterone and DTX metabolism (twofold increase in half-life) by PPL was comparable to the standard CYP3A4 inhibitor, cyclosporine A. P-gp efflux ratio of DTX across caco-2 monolayer was reduced from 2.37 to 1.52 on co-incubation with PPL. The IC50 value of DTX was reduced three to five times and combination index values in all the cell lines were below 0.6. PPL at non-cytotoxic concentration showed significant enhancement of the antimigration effect of DTX. Expression of tumor markers such as survivin, bcl2, C-myc, and cyclin D1 were downregulated to a great extent with enhanced p53 expression when treated with combination instead of individual drug. Co-treatment with PPL led to 1.68-fold enhancement in DTX bioavailability in SD rats. PPL could be a potential candidate in overcoming the obstacles associated with oral DTX delivery with synergistic anticancer activity. PMID- 26372814 TI - Integrin alpha9 gene promoter is hypermethylated and downregulated in nasopharyngeal carcinoma. AB - Epigenetic silencing of tumor suppressor genes (TSGs) by promoter methylation can be an early event in the multi-step process of carcinogenesis. Human chromosome 3 contains clusters of TSGs involved in many cancer types including nasopharyngeal carcinoma (NPC), the most common cancer in Southern China. Among ten candidate TSGs identified in chromosome 3 using NotI microarray, ITGA9 and WNT7A could be validated. 5'-aza-2' deoxycytidine treatment restored the expression of ITGA9 and WNT7A in two NPC cell lines. Immunostaining showed strong expression of these genes in the membrane and cytoplasm of adjacent control nasopharyngeal epithelium cells, while they were weakly expressed in NPC tumor cells. The ITGA9 promoter showed marked differentially methylation between tumor and control tissue, whereas no differentially methylation could be detected for the WNT7A promoter. The expression level of ITGA9 in NPC tumors was downregulated 4.9-fold, compared to the expression in control. ITGA9 methylation was detected by methylation specific PCR (MSP) in 56% of EBV positive NPC-cases with 100% specificity. Taken together, this suggests that ITGA9 might be a TSG in NPC that is involved in tumor cell biology. The possibility of using ITGA9 methylation as a marker for early detection of NPC should further be explored. PMID- 26372818 TI - Epidemiology and Diagnosis of Helicobacter pylori infection. AB - During the period reviewed, prevalence studies were essentially performed in less economically advanced countries and a high prevalence was found. The traditional risk factors for Helicobacter pylori positivity were mostly found. Transmission studied by molecular typing showed a familial transmission. The eventual role of water transmission was explored in several studies with controversial results. Concerning diagnosis, most of the invasive and noninvasive methods used for the diagnosis of H. pylori infection are long standing with efficient performance. The most interesting recent improvements in H. pylori diagnosis include advances in endoscopy, developments in molecular methods, and the introduction of omics based techniques. Interpretation of old or newer method should take into account the pretest probability and the prevalence of H. pylori in the population under investigation. PMID- 26372819 TI - Pathogenesis of Helicobacter pylori Infection. AB - Three decades have passed since Warren and Marshall described the successful isolation and culture of Helicobacter pylori, the Gram-negative bacterium that colonizes the stomach of half the human population worldwide. Although it is documented that H. pylori infection is implicated in a range of disorders of the upper gastrointestinal tract, as well as associated organs, many aspects relating to host colonization, successful persistence, and the pathophysiological mechanisms of this bacteria still remain controversial and are constantly being explored. Unceasing efforts to decipher the pathophysiology of H. pylori infection have illuminated the crucially important contribution of multifarious bacterial factors for H. pylori pathogenesis, in particular the cag pathogenicity island (PAI), the effector protein CagA, and the vacuolating cytotoxin VacA. In addition, recent studies have provided insight into the importance of the gastrointestinal microbiota on the cumulative pathophysiology associated with H. pylori infection. This review focuses on the key findings of publications related to the pathogenesis of H. pylori infection published during the last year, with an emphasis on factors affecting colonization efficiency, cagPAI, CagA, VacA, and gastrointestinal microbiota. PMID- 26372820 TI - Inflammation, Immunity, and Vaccines for Helicobacter pylori Infection. AB - During the last year, a variety of studies have been published that increases our understanding of the basic mechanisms of immunity and inflammation in Helicobacter pylori infection and progression to gastric cancer. Innate immune regulation and epithelial cell response were covered by several studies that contribute with new insights in the host response to H. pylori infection. Also, the adaptive immune response to H. pylori and particularly the role of IL-22 have been addressed in some studies. These advances may improve vaccine development where new strategies have been published. Two major studies analyzed H. pylori genomes of 39 worldwide strains and looked at the protein profiles. In addition, multi-epitope vaccines for therapeutic use have been investigated. Studies on different adjuvants and delivery systems have also given us new insights. This review presents articles from the last year that reveal detailed insight into immunity and regulation of inflammation, the contribution of immune cells to the development of gastric cancer, and understanding mechanisms of vaccine-induced protection. PMID- 26372821 TI - Helicobacter pylori and Nonmalignant Diseases. AB - Helicobacter pylori is responsible for most peptic ulcers, plays a role in functional dyspepsia and is thought by some to influence the course of gastroesophageal reflux disease. This article addresses recent studies that have been published in connection with these diseases. H. pylori-associated peptic ulcer is declining in prevalence but the incidence of perforation and bleeding remains high especially in the elderly. All H. pylori associated peptic ulcers should be treated by eradication of the infection. Dyspepsia is a common disorder that affects up to 25% of the population. About 8% of cases that are infected with H. pylori will respond to treatment of the infection. The association between H. pylori and gastroesophageal reflux disease continues to be debated, a number of studies have shown that there is a negative association between H. pylori infection and Gastroesophageal reflux disease but treatment of H. pylori has not been shown to induce reflux or to affect the response to medication. Gastric atrophy is known to extend when acid suppression is used in infected patients implying that H. pylori treatment should be used in infected patients who are to undergo long-term Proton Pump Inhibitor therapy. PMID- 26372822 TI - Pathogenesis of Gastric Cancer. AB - Gastric cancer (GC) is the fifth most common malignancy and the third leading cause of cancer-related death worldwide. GC is a heterogeneous disease and the endpoint of a long multistep process largely influenced by Helicobacter pylori infection, genetic susceptibility, and environmental factors. In a subset of GC cases, infection with the Epstein-Barr virus (EBV) may also be involved. The development of GC is the consequence of the accumulation of multiple epi/genetic changes during the patient's lifetime that will result in oncogenic activation and/or tumor suppressor pathways' inactivation. This review will focus on the most recent updates on the characterization of the molecular phenotypes of sporadic and hereditary GC. This article will also update the most recent findings on the relationship between H. pylori infection and stem cells at the origin of GC. The understanding of the molecular genetics underlying gastric carcinogenesis is of paramount importance to identify novel potential targets for the development of screening and prognostic markers that can be clinically valuable for the management of GC patients and for the design of clinical trials. PMID- 26372823 TI - Helicobacter pylori and Gastrointestinal Malignancies. AB - Helicobacter pylori infection is the principal trigger of gastric carcinogenesis and gastric cancer (GC) and remains the third leading cause of cancer-related death in both sexes worldwide. In a big Japanese study, the risk of developing GC in patients with peptic ulcer disease who received H. pylori eradication therapy and annual endoscopic surveillance for a mean of 9.9 years was significantly lower after successful eradication therapy compared to the group with persistent infection (0.21%/year and 0.45%/year, respectively, p = .049). According to a recent meta-analysis, H. pylori eradication is insufficient in GC risk reduction in subjects with advanced precancerous conditions (i.e., intestinal metaplasia and dysplasia). A microsimulation model suggested screening smokers over the age of 50 in the U.S. for serum pepsinogens. This would allow to detect advanced gastric atrophy with endoscopic follow-up of subjects testing positive as a cost effective strategy to reduce GC mortality. In a Taiwanese study, the anti-H. pylori IgG-based test-and-treat program had lower incremental cost-effectiveness ratios than that with (13)C-urea breath test in both sexes to prevent GC whereas expected years of life lost for GC were higher and the incremental cost effectiveness ratios of test-and-treat programs were more cost-effective in young adults (30-69 years old) than in elders (>70 years old). With respect to gastrointestinal malignancies other than GC, a meta-analysis confirmed the inverse association between H. pylori infection and esophageal adenocarcinoma. In a Finnish study, H. pylori seropositivity was associated with an increased risk of biliary tract cancers (multivariate adjusted OR 2.63; 95% CI: 1.08-6.37), another meta-analysis showed a slightly increased rate of pancreatic cancer in patients with CagA-negative strains (OR: 1.30; 95% CI: 1.02-1.65), whereas current data suggest that the association between H. pylori and colorectal neoplasms may be population dependent. PMID- 26372824 TI - Extragastric Diseases and Helicobacter pylori. AB - The extragastric manifestations of Helicobacter pylori infection still remain a very strong topic throughout the H. pylori world. Indeed, H. pylori may interfere with many biological processes, both inside and outside of the stomach, possibly influencing or determining the occurrence of many diseases outside of the stomach. While its role in idiopathic thrombocytopenic purpura and sideropenic anemia has already been recognized, emerging evidence suggests that H. pylori may increase the risk of acute coronary syndrome, contribute to insulin resistance and be associated with neurodegenerative, respiratory, and other miscellaneous disorders previously associated with other conditions. Different pathogenic mechanisms have been hypothesized, including the induction of a low-grade inflammatory state and the occurrence of molecular mimicry mechanisms. This review summarizes the results of the most relevant studies published on this topic in the last year. PMID- 26372825 TI - Helicobacter pylori Infection in Pediatrics. AB - This review includes the main pediatric studies published from April 2014 to March 2015. The host response of Treg cells with increases in FOXP3 and TGF-beta1 combined with a reduction in IFN-gamma by Teff cells may contribute to Helicobacter pylori susceptibility in children. Genotypic variability in H. pylori strains influences the clinical manifestation of the infection. Helicobacter pylori infection is associated with variables indicative of a crowded environment and poor living conditions, while breast-feeding has a protective effect. Intrafamilial infection, especially from mother to children and from sibling to sibling, is the dominant transmission route. Studies showed conflicting results regarding the association between H. pylori infection and iron deficiency anemia. One study suggests that H. pylori eradication plays a role in the management of chronic immune thrombocytopenic purpura in H. pylori infected children and adolescents. The prevalence of H. pylori was higher in chronic urticaria patients than in controls and, following H. pylori eradication, urticarial symptoms disappeared. An inverse relationship between H. pylori infection and allergic disease was reported. Antibiotic resistance and insufficient compliance to treatment limit the efficacy of eradication therapy. Sequential therapy had no advantage over standard triple therapy. In countries where H. pylori infection is prevalent, studies focusing on virulence factors and antibiotic susceptibility may provide anticipation of the prognosis and may be helpful to reduce morbidity and mortality. PMID- 26372826 TI - Treatment of Helicobacter pylori Infection 2015. AB - Many interesting articles have been published from many parts of the world over the last year assessing different issues around Helicobacter pylori eradication therapy. This article will address the published literature over the last year pertaining to the topic of treatment of H. pylori infection. The main themes that emerge are assessing the efficacy of standard triple therapy, as well as exploring new first-line treatments, mainly optimized nonbismuth- and bismuth containing quadruple therapies with some promising data also emerging on dual therapy. There was also considerable progress in investigating antibiotic resistance rates with much more data emerging from varied parts of the world compared to recent years. There have also been advances in the use of adjunctive therapies, especially probiotic therapies. Undoubtedly, the eradication of H. pylori remains a worthwhile goal to alleviate the burden of diseases caused by the complications of this infection, including dyspepsia, peptic ulcer disease, and gastric cancer. PMID- 26372828 TI - Gastric Microbiota. AB - After the discovery of Helicobacter pylori in 1983, the stomach was no longer considered a sterile environment. In 2015, evolving data shows that H. pylori is not the only inhabitant of the gastric mucosa. Using culture-independent methods of analysis, a non-H. pylori microbial community has been recently observed in the human stomach, the so-called human gastric microbiota, along with H. pylori itself. Increasing evidence supports the hypothesis that although H. pylori may be the most relevant, it is not the only local bacterial culprit leading to gastric diseases. Further studies are warranted to offer a better picture of the role and functions of gastric microbiota and to identify the best therapeutic modulators of gut microbiota for the management of gastric diseases. PMID- 26372827 TI - The Other Helicobacters. AB - In the past year, a substantial number of (putative) novel Helicobacter species have been described, including Helicobacter himalayensis colonizing the Himalayan marmot and Helicobacter apodemus, colonizing the Korean striped field mouse. In addition, a putative novel gastric Helicobacter species was identified in wild gorillas and chimpanzees, for which the name "Candidatus H. homininae" was proposed. A high incidence of gastric non-H. pylori Helicobacter infection was described in China and multiple case reports have described the involvement of enterohepatic Helicobacter species, especially Helicobacter cinaedi, in a wide range of diseases. Several studies in rodent models further elucidated the mechanisms underlying the development of gastric mucosa-associated lymphoid tissue lymphoma during infection with gastric non-H. pylori Helicobacters. The effects of infection with gastric Helicobacters on the development of neuroinflammation were investigated and several enterohepatic Helicobacter species were shown to affect the composition of the gut microbiota, to influence vaccine efficiency as well as the progression of cancer in distant sites of the body. PMID- 26372830 TI - ABO-Incompatible Adult Living Donor Liver Transplantation Under the Desensitization Protocol With Rituximab. AB - ABO incompatibility is no longer considered a contraindication for adult living donor liver transplantation (ALDLT) due to various strategies to overcome the ABO blood group barrier. We report the largest single-center experience of ABO incompatible (ABOi) ALDLT in 235 adult patients. The desensitization protocol included a single dose of rituximab and total plasma exchange. In addition, local graft infusion therapy, cyclophosphamide, or splenectomy was used for a certain time period, but these treatments were eventually discontinued due to adverse events. There were three cases (1.3%) of in-hospital mortality. The cumulative 3 year graft and patient survival rates were 89.2% and 92.3%, respectively, and were comparable to those of the ABO-compatible group (n = 1301). Despite promising survival outcomes, 17 patients (7.2%) experienced antibody-mediated rejection that manifested as diffuse intrahepatic biliary stricture; six cases required retransplantation, and three patients died. ABOi ALDLT is a feasible method for expanding a living liver donor pool, but the efficacy of the desensitization protocol in targeting B cell immunity should be optimized. PMID- 26372832 TI - Corrigendum. PMID- 26372831 TI - Study of two tungstates Ca0.5 Cd0.5 WO4 and Ca0.2 Cd0.8 WO4 by transmission electron microscopy. AB - To better understand the role of crystal structures and local disorder in the photonic properties of the system (1 - x)CaWO4 - xCdWO4 with 0 < x < 1, two specific phases with compositions x = 0.5 (scheelite phase) and 0.8 (wolframite phase) have been studied by scanning and transmission electron microscopies. High resolution electron microscopy images and image simulations, associated with X ray diffraction data, allowed confirming the lattices and space groups I41 /a and P2/c of the two scheelite and wolframite phases, at the local scale. The electron microscopy data show the existence of a high degree of crystallization associated with statistical distribution of Ca or Cd atoms on a Ca1- x Cdx site in each lattice. PMID- 26372833 TI - Severe rash associated with vemurafenib administration following nivolumab therapy. PMID- 26372834 TI - Reply to: "need to consider full societal impact of hepatitis B virus-positive donors". PMID- 26372835 TI - Transposition of exercise protocols: cardiovascular response to exercise in patients with transposition of the great arteries. PMID- 26372836 TI - Twenty-five years of CLC chloride transport proteins. PMID- 26372837 TI - Planning for Uncertainty and Fallbacks Can Increase the Number of Transplants in a Kidney-Paired Donation Program. AB - A kidney-paired donation (KPD) pool consists of transplant candidates and their incompatible donors, along with nondirected donors (NDDs). In a match run, exchanges are arranged among pairs in the pool via cycles, as well as chains created from NDDs. A problem of importance is how to arrange cycles and chains to optimize the number of transplants. We outline and examine, through example and by simulation, four schemes for selecting potential matches in a realistic model of a KPD system; proposed schemes take account of probabilities that chosen transplants may not be completed as well as allowing for contingency plans when the optimal solution fails. Using data on candidate/donor pairs and NDDs from the Alliance for Paired Donation, the simulations extend over 8 match runs, with 30 pairs and 1 NDD added between each run. Schemes that incorporate uncertainties and fallbacks into the selection process yield substantially more transplants on average, increasing the number of transplants by as much as 40% compared to a standard selection scheme. The gain depends on the degree of uncertainty in the system. The proposed approaches can be easily implemented and provide substantial advantages over current KPD matching algorithms. PMID- 26372839 TI - Tacrolimus and oral lichen planus. Possible absorption after mucosal application? PMID- 26372840 TI - A Picture is Worth......Turning into Quantitative Data! PMID- 26372838 TI - Voriconazole Exposure and Risk of Cutaneous Squamous Cell Carcinoma, Aspergillus Colonization, Invasive Aspergillosis and Death in Lung Transplant Recipients. AB - Voriconazole is a triazole antifungal used to prevent and treat invasive fungal infections after lung transplantation, but it has been associated with an increased risk of developing cutaneous squamous cell carcinoma (SCC). Despite widespread use, there are no clear guidelines for optimal prophylactic regimens that balance the competing risks and benefits. We conducted a retrospective cohort study of all lung transplant recipients at the University of California, San Francisco, who were transplanted between October 1991 and December 2012 (n = 455) to investigate whether voriconazole exposure affected development of SCC, Aspergillus colonization, invasive aspergillosis and all-cause mortality. Voriconazole exposure was associated with a 73% increased risk of developing SCC (hazard ratio [HR] 1.73; 95% confidence interval [CI]: 1.04-2.88; p = 0.03), with each additional 30-day exposure at the standard dose increasing the risk by 3.0% (HR 1.03; 95% CI: 1.02-1.04; p < 0.001). Voriconazole exposure reduced risk of Aspergillus colonization by 50% (HR 0.50; 95% CI: 0.34-0.72; p < 0.001), but we were underpowered to detect risk reduction for invasive aspergillosis. Voriconazole exposure significantly reduced all-cause mortality among subjects who developed Aspergillus colonization (HR 0.34; 95% CI: 0.13-0.91; p = 0.03) but had no significant impact on those without colonization. Physicians should consider patient-specific factors that modify the potential risks and benefits of voriconazole for the care of lung transplant recipients. PMID- 26372842 TI - s-Ethyl Cysteine and s-Methyl Cysteine Protect Human Bronchial Epithelial Cells Against Hydrogen Peroxide Induced Injury. AB - Protective effects and actions from s-ethyl cysteine (SEC) and s-methyl cysteine (SMC) for BEAS-2B cells were examined. BEAS-2B cells were pretreated with SEC or SMC at 4, 8, or 16 MUmol/L, and followed by hydrogen peroxide (H2 O2 ) treatment. Data showed that H2 O2 enhanced Bax, caspase-3 and caspase-8 expression, and declined Bcl-2 expression. However, SEC or SMC dose-dependently decreased caspase 3 expression and reserved Bcl-2 expression. H2 O2 increased reactive oxygen species (ROS) production, and lowered glutathione level, glutathione peroxide, and glutathione reductase activities in BEAS-2B cells. SEC or SMC pretreatments reduced ROS generation, and maintained glutathione redox cycle in those cells. H2 O2 upregulated the expression of both p47(phox) and gp91(phox) . SEC and SMC downregulated p47(phox) expression. SEC or SMC at 8 and 16 MUmol/L decreased H2 O2 -induced release of inflammatory cytokines. H2 O2 stimulated the activation of nuclear factor-kappaB (NF-kappaB) and mitogen-activated protein kinase. SEC and SMC pretreatments dose-dependently downregulated NF-kappaB p65 and p-p38 expression. Pyrrolidine dithiocarbamate or SB203580 inhibited NF-kappaB activation and p38 phosphorylation; thus, SEC or SMC pretreatments failed to affect protein expression of these factors. These novel findings suggest that SEC or SMC could protect bronchial cells and benefit respiratory epithelia stability and functions. PMID- 26372844 TI - Fluorescent Nanoparticles from Several Commercial Beverages: Their Properties and Potential Application for Bioimaging. AB - The presence of nanoparticles in beverages has raised great concern in terms of potential impacts to consumer health. Herein, carbon dots in beverages kvass, pony malta, pilsner beer, Vivant Storm, and Profit were identified. They were shown to have a strong fluorescence under the excitation of ultraviolet light. The emission peaks shift to longer wavelengths accompanied by a remarkable fluorescence intensity decrease. The carbon dots are in the nanosized range and roughly spherical in appearance. Elemental analysis by X-ray photoelectron spectroscopy demonstrated the composition of Kvass carbon dots to be C 83.17%, O 13.83%, and N 3.00%. No cytotoxicity was found at concentrations up to 20 mg/mL for human tongue squamous carcinoma cells, and they can be directly applied in both carcinoma and onion epidermal cell imaging. This work represents the first report of the carbon dots present in beverages, providing valuable insights into these nanoparticles for future biological imaging. PMID- 26372845 TI - Morphological Changes Caused by Streptozotocin-Induced Diabetes in the Healthy Gingiva of Rats. AB - BACKGROUND AND OBJECTIVE: Epidemiologic and clinical studies have indicated that diabetes is a risk factor for periodontal disease progression. The aim of the present study was to evaluate the morphological changes of gingiva in streptozotocin diabetic rats. MATERIAL AND METHODS: 30 male Wistar rats that weighed 250-300 g were used in this study. The animals were randomly divided into 2 groups, one with streptozotocin-induced diabetes and another one with healthy (non-diabetic) animals. All rats were sacrificed after 21 days, and their maxillary first molars with surrounding tissues were observed morphological analyses. RESULTS: In this study, it was observed that the epithelial thickness was greater in the diabetes group, compared to the control group. The statistical comparison of the diabetes and control groups for the thickness of each of the layers of the epithelium demonstrated that the thickness of the keratinized (corneum), granular and basal layers had significantly increased in the diabetic animals. Furthermore, the diabetes group displayed a decrease in the height of the connective tissue papillae, which was found to be statistically insignificant. Another important finding detected in the diabetes group was the congestion of the gingival capillaries, which showed that blood circulation is impaired in diabetes cases. CONCLUSION: On the basis of the results obtained in this study, it was concluded that streptozotocin-induced diabetes may increase predisposition to periodontal disease by causing morphological changes in the periodontal tissues. PMID- 26372846 TI - Significance of MPV, RDW with the Presence and Severity of Metabolic Syndrome. AB - PURPOSE: Metabolic syndrome (MS) is a multiplex risk factor that arises from insulin resistance accompanying abnormal adipose deposition and function. It is a risk factor for coronary heart disease, as well as for diabetes, fatty liver, and several cancers. Recent studies showed that there was a correlation between inflammatory mediators and MS. The aim of this study was to investigate the relationship between the MS and new inflammatory markers as mean platelet volume (MPV) and red blood cell distribution width (RDW), they are simple and reliable indicators of inflammation. METHOD: 200 patients who met the MS criteria and other 100 age- and sex-matched control subjects were included in this randomized controlled trial. Patients were classified into 2 groups each 100 subjects based on the number of MS criteria: group 1 (patients with 3 MS criteria), group 2 (patients with 5 MS criteria). MPV and RDW were calculated from complete blood count. RESULTS: Patients with MS had significantly higher MPV and RDW correspondingly compared to those without MS. (MPV: 8.4+/-0.61 v 8.80+/-0.60, 9.56+/-0.48, respectively, p<0.001) (RDW:12.38+/-0.77, 13.15+/-062, 13.90+/ 0.55). Moreover, patients meeting 5 MS criteria had higher MPV and RDW than those meeting 3 criteria (p<0.001) and 0.000, respectively) CONCLUSION: The present study indicated, for the first time, a significant correlation between the 2 criteria of MS and inflammation based on these new markers that should be simple and reliable indicator of inflammation. PMID- 26372847 TI - Different Effects of Metformin on the Hypothalamic-Pituitary-Thyroid Axis in Bromocriptine- and Cabergoline-treated Patients with Hashimoto's Thyroiditis and Glucose Metabolism Abnormalities. AB - Metformin was found to reduce serum thyrotropin levels in patients with hypothyroidism. This effect was less pronounced if patients were additionally treated with bromocriptine. The study included 39 premenopausal women with autoimmune thyroiditis and thyrotropin levels exceeding 3.0 mU/L. All patients had been treated for at least 6 months with bromocriptine (5.0-7.5 mg daily) or cabergoline (0.5-1.0 mg weekly). Because of coexisting type 2 diabetes or impaired glucose tolerance, they were then given metformin (1.7-2.55 g daily). Glucose homeostasis markers, thyroid antibody titers, as well as serum levels of thyrotropin, total and free thyroid hormones and prolactin were determined before and after 6 months of metformin treatment. At baseline, cabergoline-treated patients were less insulin resistant as well as tended to have lower levels of prolactin than bromocriptine-treated patients. Although in both treatment groups, metformin decreased plasma levels of fasting and post-challenge plasma glucose and improved insulin receptor sensitivity, this effect was more prominent in patients receiving cabergoline. However, only in bromocriptine-treated patients, metformin decreased serum thyrotropin and this effect reached the level of significance in a subgroup of patients with subclinical hypothyroidism. Neither in cabergoline- nor in bromocriptine-treated patients, metformin affected thyroid hormone levels and thyroid antibody titers. Our results indicate that the effect of metformin on hypothalamic-pituitary-adrenal axis activity is partially determined by endogenous dopaminergic tone, thyrotrope activity and insulin sensitivity. PMID- 26372848 TI - Standardization of FT4 and Harmonization of TSH Measurements--A Request for Input from Endocrinologists and Other Physicians. PMID- 26372849 TI - Application of Laser Capture Microdissection and 16S rRNA Gene Polymerase Chain Reaction in the Analysis of Bacteria Colonizing the Intestinal Tissue of Neonates With Necrotizing Enterocolitis. AB - BACKGROUND: Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in newborns. However, the pathogenesis of NEC remains unclear because most bacterial characterizations of alleged pathogens have been performed via the analysis of human fecal samples and experimental animal studies. The objective is to investigate the microbial composition of NEC using inflamed intestinal tissue surgically removed from neonates diagnosed with NEC (n = 18). METHODS: We obtained intestinal tissues via a combination of laser capture microdissection and Gram staining, which was used to mark individual bacteria. Tissues with congenital intestinal atresia (n = 7) served as control specimens. An analysis of the 16S rRNA of each sample was performed via polymerase chain reaction denaturing gradient gel electrophoresis. RESULTS: Numerous bacteria were observed in the inflamed intestinal wall tissue samples obtained from neonates with NEC following Gram staining and examination under an optical microscope. The total number of types detected by polymerase chain reaction-denaturing gradient gel electrophoresis was 12.17 +/- 2.83 per infant with NEC, whereas only 2.57 +/- 1.81 types were detected in each infant with congenital intestinal atresia. Proteobacteria had the highest constituent ratio (188 of 285) of all detected clone sequences in the NEC group. Additionally, Pseudomonas sp., Acinetobacter sp., Klebsiella sp., Clostridium sp., Ochrobactrum sp. and Arcobacter sp. were detected only in the NEC group. CONCLUSIONS: The combination of Gram staining and laser capture microdissection was a reliable method to obtain and prepare tissue samples for processing. NEC was associated with multiple species of bacteria, and microflora within the disease-affected sites may be relatively specific and stable. Proteobacteria demonstrated the highest constituent ratio. Our observations warrant closer examination of the 6 bacterial genera that were only detected in NEC, particularly Clostridium sp., which may be closely correlated with pneumatosis intestinalis. PMID- 26372850 TI - Polyfunctional T-Cell Signatures to Predict Protection from Cytomegalovirus after Lung Transplantation. AB - RATIONALE: Cytomegalovirus (CMV), which is one of the most common infections after lung transplantation, is associated with chronic lung allograft dysfunction and worse post-transplantation survival. Current approaches for at-risk patients include a fixed duration of antiviral prophylaxis despite the associated cost and side effects. OBJECTIVES: We sought to identify a specific immunologic signature that predicted protection from subsequent CMV. METHODS: CMV-seropositive lung transplantation recipients were included in the discovery (n = 43) and validation (n = 28) cohorts. Polyfunctional CMV-specific immunity was assessed by stimulating peripheral blood mononuclear cells with CMV pp65 or IE-1 peptide pools and then by measuring T-cell expression of CD107a, IFN-gamma, tumor necrosis factor-alpha (TNF-alpha), and IL-2. Recipients were prospectively monitored for subsequent viremia. A Cox proportional hazards regression model that considered cytokine responses individually and in combination was used to create a predictive model for protection from CMV reactivation. This model was then applied to the validation cohort. MEASUREMENTS AND MAIN RESULTS: Using the discovery cohort, we identified a specific combination of polyfunctional T-cell subsets to pp65 that predicted protection from subsequent CMV viremia (concordance index 0.88 [SE, 0.087]). The model included both protective (CD107a( )/IFN-gamma(+)/IL-2(+)/TNF-alpha(+) CD4(+) T cells, CD107a(-)/IFN-gamma(+)/IL 2(+)/TNF-alpha(+) CD8(+) T cells) and detrimental (CD107a(+)/IFN-gamma(+)/IL-2( )/TNF-alpha(-) CD8(+) T cells) subsets. The model was robust in the validation cohort (concordance index 0.81 [SE, 0.103]). CONCLUSIONS: We identified and validated a specific T-cell polyfunctional response to CMV antigen stimulation that provides a clinically useful prediction of subsequent cytomegalovirus risk. This novel diagnostic approach could inform the optimal duration of individual prophylaxis. PMID- 26372852 TI - Microstructural Evolution of Nanocrystalline Diamond Films Due to CH4/Ar/H2 Plasma Post-Treatment Process. AB - Plasma post-treatment process was observed to markedly enhance the electron field emission (EFE) properties of ultrananocrystalline diamond (UNCD) films. TEM examinations reveal that the prime factor which improves the EFE properties of these films is the coalescence of ultrasmall diamond grains (~5 nm) forming large diamond grains about hundreds of nanometers accompanied by the formation of nanographitic clusters along the grain boundaries due to the plasma post treatment process. OES studies reveal the presence of large proportion of atomic hydrogen and C2 (or CH) species, which are the main ingredients that altered the granular structure of the UNCD films. In the post-treatment process, the plasma interacts with the diamond films by a diffusion process. The recrystallization of diamond grains started at the surface region of the material, and the interaction zone increased with the post-treatment period. The entire diamond film can be converted into a nanocrystalline granular structure when post-treated for a sufficient length of time. PMID- 26372851 TI - Zinc oxide nanostructure-modified textile and its application to biosensing, photocatalysis, and as antibacterial material. AB - Recently, one-dimensional nanostructures with different morphologies (such as nanowires, nanorods (NRs), and nanotubes) have become the focus of intensive research, because of their unique properties with potential applications. Among them, zinc oxide (ZnO) nanomaterials has been found to be highly attractive, because of the remarkable potential for applications in many different areas such as solar cells, sensors, piezoelectric devices, photodiode devices, sun screens, antireflection coatings, and photocatalysis. Here, we present an innovative approach to create a new modified textile by direct in situ growth of vertically aligned one-dimensional (1D) ZnO NRs onto textile surfaces, which can serve with potential for biosensing, photocatalysis, and antibacterial applications. ZnO NRs were grown by using a simple aqueous chemical growth method. Results from analyses such as X-ray diffraction (XRD) and scanning electron microscopy (SEM) revealed that the ZnO NRs were dispersed over the entire surface of the textile. We have demonstrated the following applications of these multifunctional textiles: (1) as a flexible working electrode for the detection of aldicarb (ALD) pesticide, (2) as a photocatalyst for the degradation of organic molecules (i.e., Methylene Blue and Congo Red), and (3) as antibacterial agents against Escherichia coli. The ZnO-based textile exhibited excellent photocatalytic and antibacterial activities, and it showed a promising sensing response. The combination of sensing, photocatalysis, and antibacterial properties provided by the ZnO NRs brings us closer to the concept of smart textiles for wearable sensing without a deodorant and antibacterial control. Perhaps the best known of the products that is available in markets for such purposes are textiles with silver nanoparticles. Our modified textile is thus providing acceptable antibacterial properties, compared to available commercial modified textiles. PMID- 26372853 TI - Selective Access to 4-Substituted 2-Aminothiazoles and 4-Substituted 5-Thiocyano 2-aminothiazoles from Vinyl Azides and Potassium Thiocyanate Switched by Palladium and Iron Catalysts. AB - A highly selective construction of 4-substituted 2-aminothiazoles and 4 substituted 5-thiocyano-2-aminothiazoles, respectively, catalyzed by palladium(II) acetate and promoted by iron(III) bromide from vinyl azides and potassium thiocyanate has been developed. Use of readily available starting materials, high selectivity, as well as mild reaction conditions make this practical method particularly attractive. PMID- 26372854 TI - Facile Synthesis of Ag Nanorods with No Plasmon Resonance Peak in the Visible Region by Using Pd Decahedra of 16 nm in Size as Seeds. AB - This article describes a seed-mediated approach to the synthesis of Ag nanorods with thin diameters and tunable aspect ratios. The success of this method is built upon our recent progress in the synthesis of Pd decahedra as uniform samples, together with controllable sizes. When used as a seed, the Pd decahedron could direct the deposition of Ag atoms along the 5-fold axis to generate a nanorod, with its diameter being determined by the lateral dimension of the seed. We were able to generate Ag nanorods with uniform diameters down to 20 nm. Under the conditions we used for growth, symmetry breaking occurred as the Ag atoms were only deposited along one side of the Pd decahedral seed to generate a Ag nanorod with the Pd seed being positioned at one of its two ends. We also systematically investigated the localized surface plasmon resonance (LSPR) properties of the Ag nanorods. With the transverse mode kept below 400 nm, the longitudinal mode could be readily tuned from the visible to the near-infrared region by varying the aspect ratio. As an important demonstration, we obtained Ag nanorods with no LSPR peak in the visible spectrum (400-800 nm), which are attractive for applications related to the fabrication of touchscreen displays, solar films, and energy-saving smart windows. PMID- 26372855 TI - High Thermoelectric Figure of Merit Values of Germanium Antimony Tellurides with Kinetically Stable Cobalt Germanide Precipitates. AB - Heterostructures that consist of a germanium antimony telluride matrix and cobalt germanide precipitates can be obtained by straightforward solid-state synthesis including simple annealing and quenching procedures. The microscale precipitates are homogeneously distributed in a matrix with pronounced "herringbone-like" nanostructure associated with very low thermal conductivities. In comparison to the corresponding pure tellurides, the figure of merit (ZT) values of heterostructured materials are remarkably higher. This is mostly due to an increase of the Seebeck coefficient with only little impact on the electrical conductivity. In addition, the phononic part of the thermal conductivity is significantly reduced in some of the materials. As a result, ZT values of ca. 1.9 at 450 degrees C are achieved. Temperature-dependent changes of the thermoelectric properties are well-understood and correlate with complex phase transitions of the telluride matrix. However, the high ZT values are retained in multiple measurement cycles. PMID- 26372856 TI - Predicting Activators and Inhibitors of the Breast Cancer Resistance Protein (ABCG2) and P-Glycoprotein (ABCB1) Based on Mechanistic Considerations. AB - Colocalized in membrane barriers, the ABC transporters ABCB1 and ABCG2 strongly contribute to multidrug resistance (MDR). Here we investigate the as yet unknown mechanisms of activation and inhibition of ABCG2. For this purpose we measured the ATPase activity of ABCG2 and ABCB1 as a function of allocrite concentration using a calibration set of 30 diverse compounds and a validation set of 23 compounds. We demonstrate that ABCG2 is activated at low and inhibited at high allocrite concentrations, yielding bell-shaped activity curves. With an ATP regeneration assay we prove that the inhibitory part is indeed due to a decrease in activity because of high allocrite load in the transporter. However, inhibition is only observed if the membrane solubility of allocrites is sufficiently high. The concentrations of half-maximum activation and inhibition are at least 10-fold lower for ABCG2 than for ABCB1. Because ABCG2 binds its allocrites with higher affinity than ABCB1, it can extract hydrophilic, nonamphiphilic, and highly charged compounds out of the lipid membrane, typically exhibiting low lipid-water partition coefficients, but is inhibited by hydrophobic, amphiphilic, and moderately charged compounds, with high lipid-water partition coefficients. In contrast, ABCB1 is barely interacting with hydrophilic compounds, but is activated by hydrophobic compounds. We show that hydrophobicity, amphiphilicity, and charge have a dual role; they predict, on the one hand, allocrites' lipid-water partition coefficient and, on the other hand, the transporters' preference for the chemical nature of allocrites. Parameters reflecting hydrophobicity, amphiphilicity, and charge are therefore sufficient for differentiating between allocrites, activators, and inhibitors of ABCB1 and ABCG2. PMID- 26372857 TI - Differential immune responses to HIV-1 envelope protein induced by liposomal adjuvant formulations containing monophosphoryl lipid A with or without QS21. AB - Liposomes have shown promise as constituents of adjuvant formulations in vaccines to parasitic and viral diseases. A particular type of liposomal construct, referred to as Army Liposome Formulation (ALF), containing neutral and anionic saturated phospholipids, cholesterol, and monophosphoryl lipid A (MPLA), has been used as an adjuvant for many years. Here we investigated the effects of physical and chemical changes of ALF liposomes on adjuvanted immune responses to CN54 gp140, a recombinant HIV-1 envelope protein. While holding the total amounts of liposomal MPLA and the gp140 antigen constant, different liposome sizes and liposomal MPLA:phospholipid molar ratios, and the effect of adding QS21 to the liposomes were compared for inducing immune responses to the gp140. For liposomes lacking QS21, higher titers of IgG binding antibodies to gp140 were induced by small unilamellar vesicle (SUV) rather than by large multilamellar vesicle (MLV) liposomes, and the highest titers were obtained with SUV having the MPLA:phospholipid ratio of 1:5.6. ALF plus QS21 (ALFQ) liposomes induced the same maximal binding antibody titers regardless of the MPLA:phospholipid ratio. ALF MLV liposomes induced mainly IgG1 and very low IgG2a antibodies, while ALF SUV liposomes induced IgG1>=IgG2a>IgG2b antibodies. Liposomes containing QS21 induced IgG1>IgG2a>IgG2b>IgG3 antibodies. ELISPOT analysis of splenocytes from immunized mice revealed that ALF liposomes induced low levels of IFN-gamma, but ALFQ induced high levels. ALF and ALFQ liposomes each induced approximately equivalent high levels of IL-4. Based on antibody subtypes and cytokine secretion, we conclude that ALF liposomes predominantly stimulate Th2, while ALFQ strongly induces both Th1 and Th2 immunity. When CN54 gp140 was adjuvanted with either ALF or ALFQ liposomes, antibodies were induced that neutralized two HIV-1 tier 1 clade C strain pseudoviruses. PMID- 26372858 TI - Immunogenicity and immunoprotection of porcine circovirus type 2 (PCV2) Cap protein displayed by Lactococcus lactis. AB - The capsid (Cap) protein, an important immunoprotective protein of porcine circovirus type 2 (PCV2), was expressed on the cell surface of the Gram-positive food-grade bacterium, Lactococcus lactis. Cap protein was fused to the peptidoglycan binding domain (known as the protein anchor domain, PA) of the lactococcal AcmA cell-wall hydrolase. The Cap protein fusion was non-covalently rebound to the surface of non-genetically modified, non-living high-binder L. lactis cells (designated Gram-positive enhancer matrix (GEM) particles). Expression of the recombinant GEM-displaying capsid protein (GEM-PA-Cap) was verified by Western blotting and immunofluorescence and transmission electron microscopy assays. To evaluate the immunogenicity of the recombinant Cap protein (rCap), 20 PCV2-seronegative piglets were immunized with the GEM-PA-Cap subunit vaccine, GEM alone, or phosphate-buffered saline (PBS, challenge control and empty control). Each group consisted of five piglets. The results showed that the level of PCV2-specific antibodies in piglets immunized with the GEM-PA-Cap subunit vaccine was significantly higher than that of the piglets immunized with GEM alone or the control group at all the time points post-vaccination (P<0.01). After challenge with the PCV2 wild-type strain, piglets that received the GEM-PA Cap subunit vaccine showed significantly higher average daily weight gain (DWG) and shorter fever duration than the other two groups (P<0.001). Furthermore, a significant reduction in the gross lung lesion scores and lymph node lesion scores was noted in the GEM-PA-Cap-immunized group compared with the scores of the GEM or PBS-treated group (P<0.01). The results suggest that recombinant rCap displayed by L. lactis GEM particles provided the piglets with significant immunoprotection from PCV2-associated disease. Thus, the novel GEM-PA-Cap subunit vaccine has potential to be considered an effective and safe candidate vaccine against PCV2 infection in piglets. PMID- 26372859 TI - Pneumococcal vaccination coverage among persons >=65 years--United States, 2013. AB - BACKGROUND: Invasive pneumococcal disease is a major cause of illness in the United States, and rates are higher among persons >=65 years. Pneumococcal vaccination has been recommended to adults >=65 years since 1997. METHODS: Data from the 2005-2013 Behavioral Risk Factor Surveillance System were analyzed. Weighted estimates of pneumococcal vaccination coverage were calculated by state and race/ethnicity and tests for linear trend were performed. RESULTS: In 2013, the median state vaccination coverage among adults >=65 years was 69.5%, and coverage ranged from 61.9% in New Jersey to 75.6% in Oregon. Coverage overall among non-Hispanic whites (71.1%) was higher than coverage for non-Hispanic blacks (57.7%), Hispanics (51.9%), and non-Hispanic persons of other race (65.4%). Coverage increased from 2005 to 2013 overall and by racial/ethnic subgroups. CONCLUSION: Although pneumococcal vaccination coverage has improved in the past several years, coverage remains below the Healthy People 2020 target of 90% and racial/ethnic disparities exist. PMID- 26372860 TI - Not just monitoring; a strategy for managing neuromuscular blockade. PMID- 26372861 TI - Patient safety vs social hierarchy - too close to call? PMID- 26372862 TI - Point-of-care testing: a standard of care? PMID- 26372863 TI - A new indicator of successful regional block? PMID- 26372864 TI - Changing double-lumen tracheal tube curvature. PMID- 26372865 TI - Macintosh laryngoscopy for double-lumen tube placement - a reply. PMID- 26372866 TI - Hypotension during spinal anaesthesia for caesarean section. PMID- 26372867 TI - The influence of vena cava occlusion on predictive haemodynamic parameters. PMID- 26372868 TI - Hypotension during spinal anaesthesia for caesarean section - a reply. PMID- 26372869 TI - Awake laparoscopic sleeve gastrectomy under paravertebral and superficial cervical plexus blockade. PMID- 26372870 TI - A solution looking for a problem? PMID- 26372872 TI - Oxygenation during difficult videolaryngoscopy. PMID- 26372871 TI - A reply. PMID- 26372873 TI - Oxygenating patients during difficult videolaryngoscopy. PMID- 26372874 TI - Measurement of forces from epidural catheter insertion. PMID- 26372875 TI - Audible medical alarms. PMID- 26372876 TI - Use of the new McGrath((r)) MAC size-1 paediatric videolaryngoscope. PMID- 26372877 TI - Duration of analgesia for hip fracture using an ED95 dose of levobupivacaine. PMID- 26372878 TI - First use of thiopental in obstetric anaesthesia. PMID- 26372879 TI - Lightwand guided insertion of laryngeal tube suction. PMID- 26372880 TI - High-Responsivity Graphene-Boron Nitride Photodetector and Autocorrelator in a Silicon Photonic Integrated Circuit. AB - Graphene and other two-dimensional (2D) materials have emerged as promising materials for broadband and ultrafast photodetection and optical modulation. These optoelectronic capabilities can augment complementary metal-oxide semiconductor (CMOS) devices for high-speed and low-power optical interconnects. Here, we demonstrate an on-chip ultrafast photodetector based on a two dimensional heterostructure consisting of high-quality graphene encapsulated in hexagonal boron nitride. Coupled to the optical mode of a silicon waveguide, this 2D heterostructure-based photodetector exhibits a maximum responsivity of 0.36 A/W and high-speed operation with a 3 dB cutoff at 42 GHz. From photocurrent measurements as a function of the top-gate and source-drain voltages, we conclude that the photoresponse is consistent with hot electron mediated effects. At moderate peak powers above 50 mW, we observe a saturating photocurrent consistent with the mechanisms of electron-phonon supercollision cooling. This nonlinear photoresponse enables optical on-chip autocorrelation measurements with picosecond-scale timing resolution and exceptionally low peak powers. PMID- 26372882 TI - Determination of the 90% effective dose (ED90) of phenylephrine for hypotension during elective cesarean delivery using a continual reassessment method. AB - OBJECTIVE: The purpose of this study was to determine, by continual reassessment, the 90% effective dose (ED90) of phenylephrine for hypotension after combined spinal-epidural anesthesia. STUDY DESIGN: Term pregnant women scheduled for elective cesarean delivery received combined spinal epidural anesthesia. Subjects received phenylephrine at one of 6 incremental doses ranging from 60 to 160MUg (n=3 for each dose). While the first cohort received a conservative, predetermined dose of 60MUg, subsequent cohorts received phenylephrine doses determined using Bayesian-based software. One of the predetermined bolus doses of phenylephrine was given in the event of both hypotension [defined as systolic blood pressure (SBP)<80% of baseline or below 100mmHg] and tachycardia [defined as heart rate >120% of baseline or >100beatsmin(-1)]. Treatment was considered successful if SBP returned to within 80% of the baseline or >=100mmHg within 2min. RESULTS: Twenty-four subjects with hypotension and tachycardia were included. T6 block was achieved within 15min in 20 patients and after additional epidural chloroprocaine in the remaining four. The estimated ED90 was 100MUg, with a response probability of 90.7% (95% CI 74.1-99.5%). Treatment was successful in 20 patients. Probability of success at each bolus dose (in MUg) was as follows: 60, 58.9%; 80, 80.3%; 100, 90.7%; 120, 95.5%; 140, 98.3%; and 160, 99.2%. CONCLUSIONS: The ED90 of a phenylephrine bolus dose for hypotension in term pregnant women is approximately 100MUg, based on continual reassessment. PMID- 26372881 TI - Immune control of oncogenic gamma-herpesviruses. AB - Human gamma-herpesviruses contain Epstein Barr virus (EBV), the first human tumor virus that was identified in man, and Kaposi Sarcoma associated herpesvirus (KSHV), one of the most recently identified human oncogenic pathogens. Both of these have co-evolved with humans to cause tumors only in a minority of infected individuals, despite their exquisite ability to establish persistent infections. In this review we will summarize the fine-tuned balance between immune responses, immune escape and cellular transformation by these viruses, which results in life long persistent, but asymptomatic infection with immune control in most virus carriers. A detailed understanding of this balance is required to immunotherapeutically reinstall it in patients that suffer from EBV and KSHV associated malignancies. PMID- 26372883 TI - Adverse events following percutaneous and surgical coronary revascularisation: Analysis of non-MACE outcomes in the Stent or Surgery (SoS) Trial. AB - OBJECTIVES: To analyse adverse events requiring or prolonging hospitalisation in the Stent or Surgery (SoS) trial. BACKGROUND: Many adverse events following coronary revascularisation are non-major adverse cardiovascular events (non MACE). Trials comparing percutaneous coronary intervention (PCI) and coronary artery bypass surgery (CABG) have reported rates of mortality and MACE only. MATERIAL AND METHODS: Comparisons between PCI and CABG groups in the SOS trial were by intention to treat. For patients with non-fatal/non-MACE, number of events per 100 patient years follow-up and duration of hospital stay were assessed. Competing risk analysis was used to illustrate temporal pattern of adverse outcomes. RESULTS: During 2 y median follow up, 1 one or more adverse event occurred in 47.3% (231) of the PCI group and 53% (265) of the CABG group (p=0.086). Non-fatal/non-MACE occurred in 11.9% of the PCI group and 38.6% of the CABG group (p<0.001). Non-fatal/non-MACE per 100 patient years follow-up was 17.49 (PCI) and 35.04 (CABG), rate ratio 2.0, 95% CI 1.7 to 2.4, p<0.001. Cumulative non-fatal/non-MACE associated hospital stays were 1387 and 3287 days in PCI and CABG groups respectively. Median duration of hospitalisation per non fatal/non-MACE was 5 days (interquartile range 2 to 11.75 days) in the PCI group and 6 days (interquartile range 2 to 12 days) in the CABG group, p=0.245. CONCLUSIONS: CABG had lower cumulative incidence of fatal or MACE outcomes, higher cumulative incidence of non-fatal/non-MACE outcomes, and longer cumulative hospitalisation periods compared to the PCI group. PMID- 26372884 TI - Risk factors for violence against women by intimate partners in Sakarya, Turkey. AB - OBJECTIVES: Intimate partner violence (IPV) is an important public health problem in many countries including Turkey, with serious short- and long-term physical and mental health consequences, as well as significant social and public health costs. To understand the violence characteristics and the individual risk factors for both the married women victims and the perpetrator partners are the objectives of this study. METHODOLOGY: 243 married women, who have consulted to hospitals and village clinics between 2008 and 2009 with the mean age of 36.76 (SD = 11.59), accepted to participate in the study voluntarily. Participants were divided into two groups as "victimized" (58.8%, n = 143) and "non-victimized" (41.2%, n = 100) women. Victimized group consisted of women who have had any type of violence from their husbands during their life. A 61-item questionnaire was prepared that included items on demographics, IPV experience, attitudes about IPV and knowledge of legal rights. RESULTS: As compared to non-victimized group, women in victimized group mostly lived in villages than in town/city centers, were illiterate, had bride-price agreement and were younger when married. Place of accommodation, age and number of pregnancies were associated with the risk of victimization. CONCLUSIONS: In order to prevent IPV, further qualitative research is required to evaluate the involved risk factors and training programs on how to behave against violence in association with the legal rights should be designed for poorly educated women in their natural settings and hospitals. PMID- 26372885 TI - Mindfulness, anxiety, and high-stakes mathematics performance in the laboratory and classroom. AB - Mindfulness enhances emotion regulation and cognitive performance. A mindful approach may be especially beneficial in high-stakes academic testing environments, in which anxious thoughts disrupt cognitive control. The current studies examined whether mindfulness improves the emotional response to anxiety producing testing situations, freeing working memory resources, and improving performance. In Study 1, we examined performance in a high-pressure laboratory setting. Mindfulness indirectly benefited math performance by reducing the experience of state anxiety. This benefit occurred selectively for problems that required greater working memory resources. Study 2 extended these findings to a calculus course taken by undergraduate engineering majors. Mindfulness indirectly benefited students' performance on high-stakes quizzes and exams by reducing their cognitive test anxiety. Mindfulness did not impact performance on lower stakes homework assignments. These findings reveal an important mechanism by which mindfulness benefits academic performance, and suggest that mindfulness may help attenuate the negative effects of test anxiety. PMID- 26372886 TI - Applying genotoxicology tools to identify environmental stressors in support of river management. AB - Although bioassay approaches are useful for identifying chemicals of potential concern, they provide little understanding of the mechanisms of chemical toxicity. Without this understanding, it is difficult to address some of the key challenges that currently face aquatic ecotoxicology. To overcome this, the toxicity potential of the water samples was assessed and surviving organisms (Physa acuta) were used for protein activity measurements and gene expression profiling by making use of complementary DNA amplified fragment length polymorphism (cDNA-AFLP) analysis. From the data it was evident that the impacts of specific pollutants (e.g. sewage) on organisms at the cellular level could be identified, and that the expressed stressor genes can be used as bioindicators/markers/genetic signatures or fingerprints during identification of point source pollution. From an ecosystem management point of view these insights could assist with the forecasting and reduction of environmental risks on catchment level by implementing suitable management interventions. PMID- 26372887 TI - A common spatial factor analysis model for measured neighborhood-level characteristics: The Multi-Ethnic Study of Atherosclerosis. AB - The purpose of this study was to reduce the dimensionality of a set of neighborhood-level variables collected on participants in the Multi-Ethnic Study of Atherosclerosis (MESA) while appropriately accounting for the spatial structure of the data. A common spatial factor analysis model in the Bayesian setting was utilized in order to properly characterize dependencies in the data. Results suggest that use of the spatial factor model can result in more precise estimation of factor scores, improved insight into the spatial patterns in the data, and the ability to more accurately assess associations between the neighborhood environment and health outcomes. PMID- 26372889 TI - Levels and temporal trend of bisphenol A in composite food samples from Canadian Total Diet Study 2008-2012. AB - Food composite samples from the Canadian Total Diet Study which was conducted each year from 2008 to 2012 rotating between different cities were analysed for bisphenol A (BPA). The overall levels of BPA in the composite food samples from each of the five years from 2008 to 2012 were similar in general with averages (range) of 7.7 ng/g (0.20-106 ng/g), 7.8 ng/g (0.26-110 ng/g), 6.9 ng/g (0.20-84 ng/g), 7.7 ng/g (0.20-105 ng/g) and 9.0 ng/g (0.15-90 ng/g) for 2008, 2009, 2010, 2011 and 2012, respectively. Levels of BPA in most of the non-canned food composite samples were low and no particular trends were observed. In contrast, the trend of BPA levels in canned food composite samples over the five years (2008-2012) varies. BPA levels in most of the canned food composite samples from 2008 to 2012 were consistent in general (e.g. canned luncheon meat: 10-18 ng/g, canned baked beans: 18-25 ng/g). While BPA levels over the five years were found to decrease for some canned food composite samples (e.g., canned fish: 109 ng/g in 2009 vs. 51 ng/g in 2012), they were also found to increase for some other canned food composite samples (e.g. canned meat soups: 90-104 ng/g in 2011-2012 vs. 29 ng/g in 2008). Thus, recent changes in can coating for food packaging to BPA-free alternatives may have not been fully reflected in all canned food products over the period from 2008 to 2012. Continued monitoring is necessary to more fully assess the potential impact on dietary exposure by the use of BPA alternatives in food contact materials. PMID- 26372888 TI - Epigenetic priming with decitabine followed by low-dose idarubicin/cytarabine has an increased anti-leukemic effect compared to traditional chemotherapy in high risk myeloid neoplasms. AB - Decitabine (DAC) is commonly used for the treatment of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Previous studies have indicated DAC sequentially combined with idarubicin was an effective treatment for myeloid neoplasms. Therefore, a clinical study was conducted of the sequential combination of DAC followed by low-dose idarubicin/cytarabine in high-risk myeloid neoplasms. A total of 30 patients with a diagnosis of high-risk MDS, AML evolving from MDS or relapsed/refractory AML were enrolled in the study. DAC was administered 20 mg/m(2) daily for 3 consecutive days. Idarubicin (3 mg/m(2)/day) was administered 24 h after the last administration of DAC for 5-7 consecutive days, combined with cytarabine (30 mg/m(2)/day) for 7-14 days. The overall complete remission rate was 66.67%. The results demonstrate that epigenetic priming with decitabine followed by low-dose idarubicin/ytarabine has an increased anti-leukemia effect compared to traditional chemotherapy in high-risk myeloid neoplasms. PMID- 26372890 TI - Statistical innovations in the medical device world sparked by the FDA. AB - The world of medical devices while highly diverse is extremely innovative, and this facilitates the adoption of innovative statistical techniques. Statisticians in the Center for Devices and Radiological Health (CDRH) at the Food and Drug Administration (FDA) have provided leadership in implementing statistical innovations. The innovations discussed include: the incorporation of Bayesian methods in clinical trials, adaptive designs, the use and development of propensity score methodology in the design and analysis of non-randomized observational studies, the use of tipping-point analysis for missing data, techniques for diagnostic test evaluation, bridging studies for companion diagnostic tests, quantitative benefit-risk decisions, and patient preference studies. PMID- 26372891 TI - Efficacy and effectiveness of live attenuated influenza vaccine in school-age children. AB - Evidence of high efficacy of live attenuated influenza vaccine (LAIV) from randomized controlled trials is strong for children 2-6 years of age, but fewer data exist for older school-age children. We reviewed the published data on efficacy and effectiveness of LAIV in children >=5 years. QUOSA (Elsevier database) was searched for articles published from January 1990 to June 2014 that included 'FluMist', 'LAIV', 'CAIV', 'cold adapted influenza vaccine', 'live attenuated influenza vaccine', 'live attenuated cold adapted' or 'flu mist'. Studies evaluated included randomized controlled trials, effectiveness and indirect protection studies. This review demonstrates that LAIV has considerable efficacy and effectiveness in school-age children. PMID- 26372893 TI - Fragment-based approaches to anti-HIV drug discovery: state of the art and future opportunities. AB - INTRODUCTION: The search for additional drugs to treat HIV infection is a continuing effort due to the emergence and spread of HIV strains resistant to nearly all current drugs. The recent literature reveals that fragment-based drug design/discovery (FBDD) has become an effective alternative to conventional high throughput screening strategies for drug discovery. AREAS COVERED: In this critical review, the authors describe the state of the art in FBDD strategies for the discovery of anti-HIV drug-like compounds. The article focuses on fragment screening techniques, direct fragment-based design and early hit-to-lead progress. EXPERT OPINION: Rapid progress in biophysical detection and in silico techniques has greatly aided the application of FBDD to discover candidate agents directed at a variety of anti-HIV targets. Growing evidence suggests that structural insights on key proteins in the HIV life cycle can be applied in the early phase of drug discovery campaigns, providing valuable information on the binding modes and efficiently prompting fragment hit-to-lead progression. The combination of structural insights with improved methodologies for FBDD, including the privileged fragment-based reconstruction approach, fragment hybridization based on crystallographic overlays, fragment growth exploiting dynamic combinatorial chemistry, and high-speed fragment assembly via diversity oriented synthesis followed by in situ screening, offers the possibility of more efficient and rapid discovery of novel drugs for HIV-1 prevention or treatment. Though the use of FBDD in anti-HIV drug discovery is still in its infancy, it is anticipated that anti-HIV agents developed via fragment-based strategies will be introduced into the clinic in the future. PMID- 26372894 TI - Limits of imagination: the 150th Anniversary of Mendel's Laws, and why Mendel failed to see the importance of his discovery for Darwin's theory of evolution. AB - Mendel is credited for discovering Laws of Heredity, but his work has come under criticism on three grounds: for possible falsification of data to fit his expectations, for getting undue credit for the laws of heredity without having ideas of segregation and independent assortment, and for being interested in the development of hybrids rather than in the laws of heredity. I present a brief review of these criticisms and conclude that Mendel deserved to be called the father of genetics even if he may not, and most likely did not, have clear ideas of segregation and particulate determiners as we know them now. I argue that neither Mendel understood the evolutionary significance of his findings for the problem of genetic variation, nor would Darwin have understood their significance had he read Mendel's paper. I argue that the limits to imagination, in both cases, came from their mental framework being shaped by existing paradigms blending inheritance in the case of Darwin, hybrid development in the case of Mendel. Like Einstein, Darwin's natural selection was deterministic; like Niels Bohr, Mendel's Laws were probabilistic-based on random segregation of trait determining "factors". Unlike Einstein who understood quantum mechanics, Darwin would have been at a loss with Mendel's paper with no guide to turn to. Geniuses in their imaginations are like heat-seeking missiles locked-in with their targets of deep interests and they generally see things in one dimension only. Imagination has limits; unaided imagination is like a bird without wings--it goes nowhere. PMID- 26372895 TI - Mobile electrodiagnostic laboratories provide substandard patient care: An educational report. AB - INTRODUCTION: Mobile electrodiagnostic (EDx) laboratories often do not appear to comply with Medicare rules or the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) standards. METHODS: The AANEM Professional Practice Committee reached a consensus based on expert opinion on the typical deficiencies of EDx studies performed by mobile EDx laboratories and made recommendations on proper performance. RESULTS: Mobile EDx laboratories should be registered as independent diagnostic testing facilities (IDTFs) and be held to the standards established by the Centers for Medicaid and Medicare Services. Testing performed in a mobile EDx laboratory is often performed: (1) without a physical exam by a qualified EDx physician; (2) without adequate physician supervision; (3) without interpretation "on site" or in "real time"; (4) without an accompanying needle electromyography study; and (5) with an excessive number of tests. CONCLUSIONS: The AANEM recommends that payers require companies that perform studies in a mobile EDx laboratory but have failed to register as an IDTF to be held to the standards listed in the federal rules. PMID- 26372897 TI - Effect of Fat Intake on the Inflammatory Process and Cardiometabolic Risk in Obesity After Interdisciplinary Therapy. AB - Changes in diet and eating behavior along with excessive consumption of sugar or fat and a sedentary lifestyle are related to increased obesity and its associated comorbidities. The aim of this study was to investigate the role of the type of macronutrients on specific health benefits associated with the weight loss in treating obesity. A total of 30 obese women (34.89+/-3.04 kg/m(2) and 43.3+/-5.34 years) participated in an interdisciplinary therapy approach to lifestyle change, which consisted of nutritional counseling, exercise, and psychological therapy for over a period of 26 weeks. The profile was obtained by anthropometric measurements and body composition by bioelectrical impedance analysis (BIA). Usual food intake was assessed with 3-day food record diaries and blood tests were used to determine metabolic and adipokines parameters. After therapy, there was significant reduction in all anthropometric and body composition variables. Food consumption also decreased while still providing adequate nutrient intake. There was significant improvement in LDL-cholesterol, PAI-1, leptin, CRP, ICAM-1, and VCAM-1. Lower dietary carbohydrate and fat intake led to weight loss. The effect of lower carbohydrate intake on weight loss is related to changes in body composition and leptin levels. Weight loss by reducing fat intake modified the inflammatory process and cardiovascular risk, indicating dietary fat as an independent predictor factor of cell adhesion molecules. Therefore, decreasing dietary fat consumption had greater impact on the inflammatory process on obese individuals. Our results show that the type of macronutrient influences the health benefits associated with weight loss. PMID- 26372898 TI - Age- and Tissue-Dependent Modulation of IGF-1/PI3K/Akt Protein Expression by Dietary Restriction in Mice. AB - Insulin-like growth factor-1 (IGF-1), a key mediator of growth hormone action in mammals, plays an important role in the regulation of cellular and tissue functions. In the present investigation, the normal age-dependent and effect of dietary restriction on the expression levels of serum IGF-1, phosphotidylinositol 3-kinase (PI3K), and protein kinase B (PKB/Akt) in the liver, kidney and skeletal muscles of 1-, 9-, and 21-month-old female mice were ascertained using ELISA and Western blot analysis. Results showed that serum IGF-1 peaks at 9-month-old and decreases in older age. Dietary restriction (DR) decreases IGF-1 in both age groups. In liver, PI3K and relative amount of phosphorylated Akt (pAkt/Akt) showed an age-dependent correlated expression level as IGF-1 protein. In kidney and skeletal muscles, PI3K levels showed no changes with age. However, pAkt/Akt ratio increased in 9-month-old mice and decreased in 21-month-old mice. In liver, DR increased the level of PI3K and pAkt/Akt ratio in 9-month-old mice, but no significant change was seen in 21-month-old mice as compared to ad libitum-fed group. In kidney and skeletal muscles, DR mice showed an increase in PI3K level in both age groups while the pAkt/Akt ratio showed no change in 9-month-old mice, but exhibited a decrease in 21-month-old mice. These results indicate that there is a tissue-specific regulation of IGF-1/PI3K/Akt during normal aging and upon DR to help maintain the metabolic status of these tissues at those phases of animal's lifespan. PMID- 26372896 TI - Changes in expression levels of ERCC1, DPYD, and VEGFA mRNA after first-line chemotherapy of metastatic colorectal cancer: results of a multicenter study. AB - Our previous study showed that administering oxaliplatin as first-line chemotherapy increased ERCC1 and DPD levels in liver colorectal cancers (CRCs) metastases. Second, whether the anti-VEGF monoclonal antibody bevacizumab alters tumoral VEGFA levels is unknown. We conducted this multicenter observational study to validate our previous findings on ERCC1 and DPD, and clarify the response of VEGFA expression to bavacizumab administration. 346 CRC patients with liver metastases were enrolled at 22 Japanese institutes. Resected liver metastases were available for 175 patients previously treated with oxaliplatin based chemotherapy (chemotherapy group) and 171 receiving no previous chemotherapy (non-chemotherapy group). ERCC1, DPYD, and VEGFA mRNA levels were measured by real-time RT-PCR. ERCC1 mRNA expression was significantly higher in the chemotherapy group than in the non-chemotherapy group (P = 0.033), and were significantly correlated (Spearman's correlation coefficient = 0.42; P < 0.0001). VEGFA expression level was higher in patients receiving bevacizumab (n = 51) than in those who did not (n = 251) (P = 0.007). This study confirmed that first-line oxaliplatin-based chemotherapy increases ERCC1 and DPYD expression levels, potentially enhancing chemosensitivity to subsequent therapy. We also found that bevacizumab induces VEGFA expression in tumor cells, suggesting a biologic rationale for extending bevacizumab treatment beyond first progression. PMID- 26372899 TI - Association between Serum Total Osteocalcin Level and Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis. AB - Studies on the association between serum total osteocalcin level and type 2 diabetes mellitus (T2DM) had reported controversial results. The aim of this study was to comprehensively assess this association through a meta-analysis. Eligible articles were identified in electronic databases from their inception through May 1, 2015. To assess the relationship between serum total osteocalcin and T2DM, a meta-analysis was performed to determine whether total osteocalcin differed obviously between individuals with and without T2DM, and whether serum total osteocalcin level was associated with the risk of T2DM. The standardized mean difference (SMD) and their 95% confidence intervals (95% CIs) for total osteocalcin between individuals with and without T2DM, and pooled odds ratios (ORs) and their 95% CI for the T2DM risk were calculated by meta-analysis. Twenty four papers fulfilled the inclusion criteria. From the pooled data, the total osteocalcin level was significantly lower among T2DM patients than controls (SMD: - 2.87; 95% CI-3.76 to - 1.98; p<0.00001), and high total osteocalcin level was significantly and independently associated with decreased risk of T2DM (OR=0.70, 95% CI 0.56-0.88; p=0.002). There was no evidence for publication bias. Serum total osteocalcin level is significantly lower in T2DM patients than controls, and total osteocalcin is inversely associated with the development of T2DM. PMID- 26372900 TI - The role of cytokine deficiencies and cytokine autoantibodies in clinical dermatology. AB - Cytokines are small, secreted proteins that are essential for promoting and maintaining a normal immune response. Upregulation of cytokines frequently occurs in autoimmune and inflammatory diseases. Conversely, several immunodeficiency, autoimmune and autoinflammatory disorders are known to occur due to a downregulation or absence of cytokines. Here, we review the diagnosis and clinical management of cytokine deficiency syndromes in dermatology. We will review the biology of cytokines, and the current approved indications for recombinant cytokines and anticytokine antibodies. We will also review the role of cytokine deficiencies and cytokine autoantibodies in immunodeficiency syndromes, as well as in autoimmune disorders. Finally, we will examine autoinflammatory disorders due to cytokine deficiencies. PMID- 26372901 TI - Inline electron holography and VEELS for the measurement of strain in ternary and quaternary (In,Al,Ga)N alloyed thin films and its effect on bandgap energy. AB - We present the use of (1) dark-field inline electron holography for measuring the structural strain, and indirectly obtaining the composition, in a wurtzite, 4-nm thick InAlGaN epilayer on a AlN/GaN/AlN/GaN multinano-layer heterosystem, and (2) valence electron energy-loss spectroscopy to study the bandgap value of five different, also hexagonal, 20-50-nm-thick InAlGaN layers. The measured strain values were almost identical to the ones obtained by other techniques for similarly grown materials. We found that the biaxial strain in the III-N alloys lowers the bandgap energy as compared to the value calculated with different known expressions and bowing parameters for unstrained layers. By contrast, calculated and experimental values agreed in the case of lattice-matched (almost unstrained) heterostructures. PMID- 26372902 TI - Preanalytical Stability of Gemcitabine and its Metabolite 2', 2'-Difluoro-2' Deoxyuridine in Whole Blood-Assessed by Liquid Chromatography Tandem Mass Spectrometry. AB - Gemcitabine (2',2'-difluoro-2'-deoxycytidine, dFdC) and metabolite (2',2' difluoro-2'-deoxyuridine, dFdU) quantification is warranted for individualized treatment strategies. Analyte stability is crucial for the validity of such quantification. We therefore studied the impact of the time interval from blood sampling to separation of plasma on gemcitabine stability. Blood from gemcitabine treated patients was drawn into tetrahydrouridine (THU)-spiked heparin and ethylenediaminetetraacetic acid tubes and kept on ice until separation. Plasma was separated sequentially up to 24 h after sampling and dFdC and dFdU were quantified by liquid chromatography tandem mass spectrometry (LC-MS/MS). The change in plasma concentrations over time was compared with the highest imprecision for concentrations above the lower limit of quantification of the LC MS/MS method. Analyte concentrations decreased slightly over time, but for samples stored for 4 h on ice, the decline was smaller than the expected analytical imprecision. After 24 h, the maximum decline was 14.0%, which exceeded the expected analytical imprecision. dFdC and dFdU stabilities were acceptable for at least 4 h when THU-spiked whole blood samples were kept on ice. This is within the scope of routine sampling procedures. Further, variations in separation time intervals within this time frame are negligible when interpreting drug concentrations. PMID- 26372903 TI - Autoimmune Pancreatitis: Avoiding Unnecessary Procedures by Following International Consensus Guidelines. PMID- 26372904 TI - Activated Schwann Cell-Like Cells on Aligned Fibrin-Poly(Lactic-Co-Glycolic Acid) Structures: A Novel Construct for Application in Peripheral Nerve Regeneration. AB - Tissue engineering approaches in nerve regeneration search for ways to support gold standard therapy (autologous nerve grafts) and to improve results by bridging nerve defects with different kinds of conduits. In this study, we describe electrospinning of aligned fibrin-poly(lactic-co-glycolic acid) (PLGA) fibers in an attempt to create a biomimicking tissue-like material seeded with Schwann cell-like cells (SCLs) in vitro for potential use as an in vivo scaffold. Rat adipose-derived stem cells (rASCs) were differentiated into SCLs and evaluated with flow cytometry concerning their differentiation and activation status [S100b, P75, myelin-associated glycoprotein (MAG), and protein 0 (P0)]. After receiving the proliferation stimulus forskolin, SCLs expressed S100b and P75; comparable to native, activated Schwann cells, while cultured without forskolin, cells switched to a promyelinating phenotype and expressed S100b, MAG, and P0. Human fibrinogen and thrombin, blended with PLGA, were electrospun and the alignment and homogeneity of the fibers were proven by scanning electron microscopy. Electrospun scaffolds were seeded with SCLs and the formation of Bungner-like structures in SCLs was evaluated with phalloidin/propidium iodide staining. Carrier fibrin gels containing rASCs acted as a self-shaping matrix to form a tubular structure. In this study, we could show that rASCs can be differentiated into activated, proliferating SCLs and that these cells react to minimal changes in stimulus, switching to a promyelinating phenotype. Aligned electrospun fibrin-PLGA fibers promoted the formation of Bungner-like structures in SCLs, which also rolled the fibrin-PLGA matrix into a tubular scaffold. These in vitro findings favor further in vivo testing. PMID- 26372905 TI - Safety and Efficacy of Modified FOLFIRINOX for Advanced Pancreatic Adenocarcinoma: A UK Single-Centre Experience. AB - OBJECTIVES: The combination of 5-fluorouracil (5-FU), irinotecan and oxaliplatin (FOLFIRINOX) is considered the first-line chemotherapy for fit patients with advanced pancreatic ductal adenocarcinoma (PDAC) but carries an unfavourable adverse event (AE) profile. We retrospectively evaluated the tolerability and efficacy of a modified FOLFIRINOX (mFOLFIRINOX) regimen: intravenous oxaliplatin 85 mg/m2, irinotecan 135 mg/m2, folinic acid 400 mg/m2 and 5-FU infusion 2,400 mg/m2 over 46 h, with routine subcutaneous filgrastim on a 14-day cycle. METHODS: Records of 18 patients with advanced PDAC who received treatment with mFOLFIRINOX were reviewed. Imaging of measurable disease was assessed for response, and survival was measured from the date of commencing chemotherapy to disease progression and/or death. RESULTS: Grade 3 or 4 AEs (n; %) included vomiting (5; 28), nausea (4; 22), diarrhoea (3; 17) and non-neutropaenic fever (3; 17). For patients with stage IV disease, 12/15 (80%) achieved at least stable disease as the best radiological response, with 7/15 (47%) objective responses. In this subgroup, median overall and progression-free survival were 9.3 months (95% CI 8.3-10.4) and 7.2 months (95% CI 4.7-9.6), respectively. CONCLUSION: Compared to full-dose FOLFIRINOX, our modified regimen resulted in lower haematological but only marginally improved non-haematological toxicity rates, with comparable efficacy outcomes. Prospective studies are required to validate these findings. PMID- 26372906 TI - Medication Use in Adults with and without Hearing Impairment. AB - The objective of this study was to determine whether hearing ability in adults is associated with medication use in general, the use of specific types of medication, or polypharmacy. In this exploratory study, data of the National Longitudinal Study on Hearing (NL-SH; n = 2,160) were used. In total, 62% of the participants reported using any medication in the past 28 days. Hearing ability in noise, as determined with an online digit-triplet speech-in-noise test, was significantly associated with (1) medication acting on the alimentary tract and metabolism (including diabetes and acid-related disorders), (2) use of calcium blockers, and (3) medication used for sensory organs. PMID- 26372907 TI - Growth Hormone Receptor Antagonist Transgenic Mice Have Increased Subcutaneous Adipose Tissue Mass, Altered Glucose Homeostasis and No Change in White Adipose Tissue Cellular Senescence. AB - BACKGROUND: Growth hormone (GH)-resistant/deficient mice experience improved glucose homeostasis and substantially increased lifespan. Recent evidence suggests that long-lived GH-resistant/deficient mice are protected from white adipose tissue (WAT) dysfunction, including WAT cellular senescence, impaired adipogenesis and loss of subcutaneous WAT in old age. This preservation of WAT function has been suggested to be a potential mechanism for the extended lifespan of these mice. OBJECTIVE: The objective of this study was to examine WAT senescence, WAT distribution and glucose homeostasis in dwarf GH receptor antagonist (GHA) transgenic mice, a unique mouse strain having decreased GH action but normal longevity. METHODS: 18-month-old female GHA mice and wild-type (WT) littermate controls were used. Prior to dissection, body composition, fasting blood glucose as well as glucose and insulin tolerance tests were performed. WAT distribution was determined by weighing four distinct WAT depots at the time of dissection. Cellular senescence in four WAT depots was assessed using senescence-associated beta-galactosidase staining to quantify the senescent cell burden, and real-time qPCR to quantify gene expression of senescence markers p16 and IL-6. RESULTS: GHA mice had a 22% reduction in total body weight, a 33% reduction in lean mass and a 10% increase in body fat percentage compared to WT controls. GHA mice had normal fasting blood glucose and improved insulin sensitivity; however, they exhibited impaired glucose tolerance. Moreover, GHA mice displayed enhanced lipid storage in the inguinal subcutaneous WAT depot (p < 0.05) and a 1.7-fold increase in extra-/intraperitoneal WAT ratio compared to controls (p < 0.05). Measurements of WAT cellular senescence showed no difference between GHA mice and WT controls. CONCLUSIONS: Similar to other mice with decreased GH action, female GHA mice display reduced age-related lipid redistribution and improved insulin sensitivity, but no change in cellular senescence. The similar abundance of WAT senescent cells in GHA and control mice suggests that any protection against generation of senescent cells afforded by decreased GH action, low insulin-like growth factor 1 and/or improved insulin sensitivity in the GHA mice may be offset by their severe adiposity, since obesity is known to increase senescence. PMID- 26372908 TI - Differential expression of HDAC and HAT genes in atrophying skeletal muscle. AB - INTRODUCTION: Histone deacetylase (HDAC) proteins, which counter the activity of histone acetyltransferases (HATs), are necessary for normal muscle atrophy in response to several pathophysiological conditions. Despite this, it remains unknown whether a common or unique transcriptional profile of HDAC and HAT genes exist during the progression of muscle atrophy. METHODS: Muscles were harvested from cast immobilized, denervated, or nutrient deprived animals for quantitative reverse transcriptase-polymerase chain reaction analysis of HDAC and HAT gene expression. RESULTS: The mRNA levels of Hdac2, Hdac4, Hdac6, Sirt1, p300, Cbp, and Pcaf increased, and Hdac7 decreased in skeletal muscle in each experimental model of muscle atrophy. Hdac1 and Hdac3 were increased only in cast immobilized and denervated muscles. CONCLUSIONS: While specific HDACs and HATs are increased in multiple models of muscle atrophy, increased expression of class I HDACs was unique to muscle disuse, reinforcing that specific HDAC inhibitors may be more effective than pan-HDAC inhibitors at countering muscle atrophy. PMID- 26372909 TI - Lupus-Prone Mice Resist Immune Regulation and Transplant Tolerance Induction. AB - The strongly immunogenic environment in autoimmune diseases such as lupus may pose a stringent barrier to transplantation. Despite available murine models of lupus, transplant tolerance in this setting has yet to be fully investigated in highly penetrant genetic models of disease. Such studies are of clear clinical importance because lupus is a transplant indication in which transplanted kidneys have a substantially increased risk of rejection including a role for recurrent nephritis. In the fully penetrant B6.SLE123 mouse, we determined that CD4 T follicular helper and germinal center B cells were significantly expanded compared with healthy controls. We traced this expansion to resistance of effector CD4 T and B cells in B6.SLE123 mice to regulation by either CD4 T regulatory cells (CD4Tregs) or CD8 T regulatory cells (CD8Tregs), despite demonstrating normal function by Tregs in this strain. Finally, we determined that B6.SLE123 mice resist anti-CD45RB-mediated tolerance induction to foreign islet allografts, even in the absence of islet autoimmunity. Overall, B6.SLE123 lupus-prone mice are highly resistant to transplant tolerance induction, which provides a new model of failed tolerance in autoimmunity that may elucidate barriers to clinical transplantation in lupus through further cellular and genetic dissection. PMID- 26372911 TI - Abstracts of the 103(rd) FDI Annual World Dental Congress September 2015. PMID- 26372910 TI - Endothelial Cell Apoptosis Induces TGF-beta Signaling-Dependent Host Endothelial Mesenchymal Transition to Promote Transplant Arteriosclerosis. AB - Endothelial cells (ECs) apoptosis is an initial event in transplant arteriosclerosis (TA), resulting in allograft function loss. To elucidate the precise mechanisms of ECs apoptosis leading to neointimal smooth muscle cells (SMCs) accumulation during TA. We induced apoptosis in cultured ECs by overexpressing p53 through lentivirus-mediated transfection. ECs apoptosis induced the production of transforming growth factor (TGF)-beta1 in both apoptotic and neighboring viable cells, leading to increased TGF-beta1 in the culture media. Conditioned media from Ltv-p53-transfected ECs further promoted transition of cultured ECs to SM-like cells by activating TGF-beta/Smad3, PI3K/Akt/mTOR, and MAPK/ERK signaling in a TGF-beta-dependent manner. In transgenic rat aorta transplantation models, inhibition of ECs apoptosis in Bcl xL(+/+) knock-in rat aortic allografts significantly reduced TGF-beta1 production both in allograft endothelia and in blood plasma, which in turn decreased accumulation of SM22alpha+ cells from transgenic recipient ECs originally marked with EGFP knock-in in neointima and alleviated TA. Systemic treatment with SIS3, AP23573, or PD98059 also prevented recipient ECs-originated SM-like cells accumulation and intima hyperplasia in aortic allografts. These data suggest that allograft EC apoptosis induced recipient endothelial-mesenchymal (smooth muscle) transition via TGF-beta signaling, resulting in recipient EC-derived SMC accumulation as a major mechanism of vascular remodeling during TA. PMID- 26372912 TI - Modern solutions and future challenges for platelet inventory management. PMID- 26372913 TI - What is the value of a blood type? PMID- 26372914 TI - Bacterial pathogen reduction requires validation under conditions of intended use. PMID- 26372916 TI - Simultaneous blood donor screening for abnormal hemoglobin levels and glycated hemoglobin (HbA1c) by high-performance liquid chromatography. PMID- 26372917 TI - An alternative method to dithiothreitol treatment for antibody screening in patients receiving daratumumab. PMID- 26372919 TI - ERRATUM. PMID- 26372918 TI - Custodes invicem custodiunt (the watchmen can watch each other). PMID- 26372920 TI - Syphilis screening, treatment and follow-up: strengths and weaknesses of the international guidelines. PMID- 26372921 TI - Nanowire-based structures for infrared to ultraviolet emitters studied by cathodoluminescence. AB - Nanowires are structures with features on the nanoscale, and it is therefore essential to study their properties on that scale. We present optical data from a variety of nanowire-based structures using cathodoluminescence imaging and spectroscopy. One important feature of nanowires is the stacking sequence of the crystal, either zincblede, wurtzite or a mix of the two. We show that this has an impact on the optical properties. In radial quantum wells, the thickness can be controlled on a monolayer level, in the case of flat side facets of the nanowires. With rough side facets, the quantum well collapses into quantum dots, as revealed by cathodoluminescence imaging. In order to extend the emission wavelength of light-emitting diodes into the ultraviolet or to cover the whole visible range, we use nanowire-seeded truncated pyramids as bases for these devices, based on either GaInN (visible) and AlGaN (ultraviolet). PMID- 26372922 TI - Issue highlights--November 2015 (88:B6). PMID- 26372923 TI - In Vivo Mobilization and Functional Characterization of Nonhuman Primate Monocytic Myeloid-Derived Suppressor Cells. AB - Increasing evidence from small animal models shows that myeloid-derived suppressor cells (MDSCs) can play a crucial role in inhibiting allograft rejection and promoting transplant tolerance. We identified CD3(-)CD20(-)HLA-DR( )CD14(+)CD33(+)CD11b(+) cells in peripheral blood of healthy rhesus macaques. These putative monocytic MDSCs constituted 2.1% +/- 1.7% of lin(-)HLA-DR(-) peripheral blood mononuclear cells. Administration of granulocyte-macrophage colony-stimulating factor (CSF) and granulocyte CSF increased their incidence to 5.3% +/- 3.4%. The total number of MDSCs that could be flow sorted from a single whole rhesus leukapheresis product was 38 +/- 13 * 10(6) (n = 10 monkeys). Freshly isolated or cryopreserved MDSCs from mobilized monkeys incorporated in cultures of anti-CD3- and anti-CD28-stimulated autologous T cells markedly suppressed CD4(+) and CD8(+) T cell proliferation and cytokine secretion (interferon gamma, IL-17A). Moreover, these MDSCs enhanced CD4(+)CD25(hi)Foxp3(+) regulatory T cell (Treg) expansion while inhibiting proliferation of activated memory T cells and increasing Treg relative to effector and terminally differentiated memory T cells. Inhibition of arginase-1, but not inducible nitric oxide synthase activity, partially reversed the inhibitory effect of the MDSCs on CD8(+) T cell proliferation. Consequently, functional MDSCs can be isolated from nonhuman primates for prospective use as therapeutic cellular vaccines in transplantation. PMID- 26372924 TI - Immune Reconstitution Inflammatory Syndrome Secondary to Mycobacterium kansasii Infection in a Kidney Transplant Recipient. AB - Nontuberculous mycobacteria (NTM) infection is a challenging diagnosis for clinicians in solid organ transplantation. Immune reconstitution inflammatory syndrome (IRIS) is so far unreported in this context. We report here the case of a renal transplant recipient who developed Mycobacterium kansasii-associated lymphadenitis complicated by IRIS while undergoing reduction of his immunosuppressive therapy. For IRIS, the patient required low-dose steroids and an increase in global immunosuppression, in association with NTM antibiotherapy. PMID- 26372925 TI - Associations of Anogenital Low-Risk Human Papillomavirus Infection With Cancer and Acquisition of HIV. AB - alpha-Mucosal human papillomavirus (HPV) types are implicated in a range of clinical conditions and categorized as "low-risk" (LR) and "high-risk" (HR) types according to their degree of association with cervical cancers. The causative role of LR HPV infection in the development of anogenital warts and in low-grade squamous intraepithelial lesions is well established. In addition, there is a growing body of evidence that infection with LR HPV types may be associated with an elevated risk of cancers and potentiation of coinfections. Prospective and case-control studies consistently report a higher risk of anogenital cancers in men and women with a history of anogenital warts. Based on currently available evidence, this higher risk may be due to shared exposure to HR HPV types or an underlying immune impairment, rather than a direct role of LR HPV types in subsequent cancer risk. Data also suggest that infection with LR HPV, HR HPV, or both may increase the risk of HIV acquisition, although the relative contribution of different HPV types is not yet known. There is also evidence implicating HPV clearance, rather than HPV infection, in increased risk of HIV acquisition. PMID- 26372926 TI - Sex Partner Meeting Places Over Time Among Newly HIV-Diagnosed Men Who Have Sex With Men in Baltimore, Maryland. AB - BACKGROUND: Sex partner meeting places may be important locales to access men who have sex with men (MSM) and implement targeted HIV control strategies. These locales may change over time, but temporal evaluations have not been performed. METHODS: The objectives of this study were to describe the frequency of report of MSM sex partner meeting places over time and to compare frequently reported meeting places in the past 5 years and past year among newly HIV-diagnosed MSM in Baltimore City, Maryland. Public health HIV surveillance data including partner services information were obtained for this study from the Baltimore City Health Department from May 2009 to June 2014. RESULTS: A total of 869 sex partner meeting places were reported, including 306 unique places. Bars/clubs (31%) and Internet-based sites (38%) were the most frequently reported meeting place types. Over the 5-year period, the percentage of bars/clubs decreased over time and the percentage of Internet-based sites increased over time. Among bars/clubs, 4 of 5 of those most frequently reported in the past 5 years were also most frequently reported in the most recent year. Among Internet-based sites, 3 of 5 of those most frequently reported in the past 5 years were also in the top 5 most frequently reported in the past year. CONCLUSION: This study provides a richer understanding of sex partner meeting places reported by MSM over time and information to health departments on types of places to access a population at high risk for HIV transmission. PMID- 26372928 TI - Screening for Sexually Transmitted Infections in Antenatal Care Is Especially Important Among HIV-Infected Women. PMID- 26372929 TI - Impact of a Brief Intervention for Substance Use on Acquisition of Sexually Transmitted Diseases Including HIV: Findings From an Urban Sexually Transmitted Disease Clinic Population. AB - BACKGROUND: Unhealthy substance use is associated with increased rates of sexually transmitted diseases (STDs), including HIV. The screening, brief intervention, and referral to treatment strategy is effective at reducing substance use over time. We investigated whether STD clinic patients who received a brief intervention (BI) had lower rates of STD/HIV acquisition over time than those who did not. METHODS: A retrospective sample of 7665 patients who screened positive for substance abuse or dependence between May 1, 2008, and December 31, 2010, was matched with STD and HIV surveillance registries for a 1-year follow-up period to determine incidence of STD and HIV infection. RESULTS: Overall, 44.6% (n = 3420) received BI; 7.0% of this population acquired a bacterial STD compared with 8.8% of persons who did not receive BI (P < 0.005). In multivariate analysis, BI had a protective effect against STD infection for men (odds ratio, 0.774; 95% confidence interval [CI], 0.63-0.96), after controlling for age, race/ethnicity, and sex of partner. There were 61 new HIV infections over the follow-up period; however, we found no significant association between BI and subsequent HIV diagnosis. CONCLUSIONS: Brief intervention is associated with a reduction in STD incidence among men who screen positive for substance abuse and should be considered as an STD prevention strategy. Further study is needed to identify mechanisms through which BI may impact STD outcomes. PMID- 26372927 TI - Chlamydia and Gonorrhea in HIV-Infected Pregnant Women and Infant HIV Transmission. AB - BACKGROUND: Sexually transmitted infections (STIs) such as Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) can lead to adverse pregnancy and neonatal outcomes. The prevalence of STIs and its association with HIV mother-to-child transmission (MTCT) were evaluated in a substudy analysis from a randomized, multicenter clinical trial. METHODOLOGY: Urine samples from HIV-infected pregnant women collected at the time of labor and delivery were tested using polymerase chain reaction testing for the detection of CT and NG (Xpert CT/NG; Cepheid, Sunnyvale, CA). Infant HIV infection was determined by HIV DNA polymerase chain reaction at 3 months. RESULTS: Of the 1373 urine specimens, 249 (18.1%) were positive for CT and 63 (4.6%) for NG; 35 (2.5%) had both CT and NG detected. Among 117 cases of HIV MTCT (8.5% transmission), the lowest transmission rate occurred among infants born to CT- and NG-uninfected mothers (8.1%) as compared with those infected with only CT (10.7%) and both CT and NG (14.3%; P = 0.04). Infants born to CT-infected mothers had almost a 1.5-fold increased risk for HIV acquisition (odds ratio, 1.47; 95% confidence interval, 0.9-2.3; P = 0.09). CONCLUSIONS: This cohort of HIV-infected pregnant women is at high risk for infection with CT and NG. Analysis suggests that STIs may predispose to an increased HIV MTCT risk in this high-risk cohort of HIV-infected women. PMID- 26372930 TI - The Significant Impact of Different Insurance Enrollment Criteria on the HEDIS Chlamydia Screening Measure for Young Women Enrolled in Medicaid and Commercial Insurance Plans. AB - OBJECTIVE: The impact of length of enrollment in a health plan on eligibility of women under the Healthcare Effectiveness Data and Information Set (HEDIS) chlamydia screening measure is not fully understood. We assessed the representativeness of the measure among the proportion of women aged 15 to 24 years with a gap in coverage for Medicaid and commercial health insurance. METHODS: Truven Health Marketscan Medicaid and commercial health insurance data from 2006 to 2012 were used to make comparisons between proportions of women with a gap in coverage to those enrolled in insurance plans for different numbers of months. RESULTS: Approximately 48% of Medicaid-insured women and 31% of commercially insured women had an at least 2-month gap that disqualified them from eligibility for inclusion in the HEDIS chlamydia screening measure. Extending eligibility to women with at least 6 months of coverage, regardless of gap, would increase the proportion of insured women included in the HEDIS measure to 76% (from 52%) for Medicaid and 83% (from 69%) for commercial insurance, without much effect on chlamydia testing rate. This would make the measure more representative of all insured women. CONCLUSIONS: The large proportion of young women who had a 2-month or greater gap in coverage in Medicaid had a significant impact on the overall representativeness of the current HEDIS chlamydia screening measure. PMID- 26372931 TI - Barriers to Bacterial Sexually Transmitted Infection Testing of HIV-Infected Men Who Have Sex With Men Engaged in HIV Primary Care. AB - BACKGROUND: Approximately 15% of HIV-infected men who have sex with men (MSM) engaged in HIV primary care have been diagnosed as having a sexually transmitted infection (STI) in the past year, yet STI testing frequency remains low. METHODS: We sought to quantify STI testing frequencies at a large, urban HIV care clinic, and to identify patient- and provider-related barriers to increased STI testing. We extracted laboratory data in aggregate from the electronic medical record to calculate STI testing frequencies (defined as the number of HIV-infected MSM engaged in care who were tested at least once over an 18-month period divided by the number of MSM engaged in care). We created anonymous surveys of patients and providers to elicit barriers. RESULTS: Extragenital gonorrhea and chlamydia testing was low (29%-32%), but the frequency of syphilis testing was higher (72%). Patients frequently reported high-risk behaviors, including drug use (16.4%) and recent bacterial STI (25.5%), as well as substantial rates of recent testing (>60% in prior 6 months). Most (72%) reported testing for STI in HIV primary care, but one-third went elsewhere for "easier" (42%), anonymous (21%), or more frequent (16%) testing. HIV primary care providers lacked testing and treatment knowledge (25%-32%) and cited lack of time (68%), discomfort with sexual history taking and genital examination (21%), and patient reluctance (39%) as barriers to increased STI testing. CONCLUSION: Sexually transmitted infection testing in HIV care remains unacceptably low. Enhanced education of providers, along with strategies to decrease provider time and increase patient ease and frequency of STI testing, is needed. PMID- 26372932 TI - Improvement of Sexually Transmitted Disease Screening Among HIV-Infected Men Who Have Sex With Men Through Implementation of a Standardized Sexual Risk Assessment Tool. AB - BACKGROUND: Screening for gonorrhea (GC) and chlamydia (CT) and syphilis among HIV-positive (HIV+) men who have sex with men (MSM) is recommended at least annually. However, significant gaps in screening coverage exist. We conducted a quality improvement intervention to determine whether informing providers of preintervention screening rates and routinizing sexual risk assessment would improve sexually transmitted disease (STD) screening in a large HIV care clinic. METHODS: In partnership with Kaiser Permanente Northern California, we developed and implemented a 10-item assessment addressing sexual and other behavioral risk factors among HIV+ MSM. We analyzed the proportion of patients screened for GC/CT and syphilis in a preintervention period (June 25-September 26, 2012) and during the intervention period (June 25-September 26, 2013). RESULTS: Of 364 HIV+ MSM seen for care during the intervention period, 47.3% completed the sexual risk assessment. Improvements in GC/CT screening and syphilis screening were observed; when comparing the preintervention period with the intervention period, the proportion of HIV+ MSM receiving GC/CT screening increased by 26.8% (31.6%-40.1%, P = 0.01) at any anatomical site and by 45% (19.5%-28.3%, P = 0.003) at the pharyngeal site. Syphilis screening significantly increased by 18.8% (48.7% 58.0%, P = 0.009). CONCLUSIONS: Overall STD screening increases were observed after this intervention that included didactic training on the urgency of STD screening needs for HIV+ MSM, a presentation of preintervention clinic STD screening data, and the implementation of self-reported sexual risk assessment. Additional efforts are needed to determine feasible ways to accurately assess the appropriateness of STD screening and success of interventions to improve STD screening. PMID- 26372933 TI - Exploring ecological, emotional and social levers of self-rated health for urban gardeners and non-gardeners: A path analysis. AB - RATIONALE: The social, emotional, and mental health benefits associated with gardening have been well documented. However, the processes underlying the relationship between garden participation and improvements in health status have not been sufficiently studied. METHODS: Using population-based survey data (n = 469 urban residents), objective street environment data, and area-level measures, this research used a path analytic framework to examine several theoretically based constructs as mediators between gardening history and self-reported health. RESULTS: The results showed that garden participation influenced health status indirectly through social involvement with one's community, perceived aesthetic appeal of the neighborhood, and perceived collective efficacy. Gardeners, compared to non-gardeners, reported higher ratings of neighborhood aesthetics and more involvement in social activities, whereas aesthetics and involvement were associated with higher ratings of collective efficacy and neighborhood attachment. Collective efficacy, but not neighborhood attachment, predicted self rated health. Gardening also directly influenced improved fruit and vegetable intake. The physical and social qualities of garden participation may therefore stimulate a range of interpersonal and social responses that are supportive of positive ratings of health. CONCLUSION: This research suggests that community planners and health professionals should aim to strengthen the social and aesthetic relationships while designing environments and policies as a way to ignite intermediate processes that may lead to improved health status. PMID- 26372935 TI - Breastfeeding motivation and Self-Determination Theory. AB - RATIONALE: In the current social climate, breastfeeding is regarded as the "gold standard" of babies' nutrition and optimal mothering. It is not surprising, therefore, that the vast majority of contemporary women begin breastfeeding after they give birth. OBJECTIVE: This paper presents two separate quantitative studies conducted in Israel which examined breastfeeding motivation and its association with maternal well-being as derived from Self-Determination Theory (SDT). In Study I, a new breastfeeding motivation scale reflecting the various SDT-informed motivations was developed. Study II sought to validate the structure of the scale and to examine the hypotheses derived from SDT. METHODS: In Study I, which took place in 2007, 130 mothers of at least one child under the age of eight years old filled out the Breastfeeding Motivation Scale. In Study II, which took place during the years 2008-2010, a different sample of 236 women were followed at three different time points: during the third trimester of pregnancy, at eight weeks postnatal, and at five months postnatal. The participants completed the Breastfeeding Motivation Scale and maternal well-being, maternal self-efficacy and maternal attachment questionnaires. RESULTS: The findings supported the structure of the Breastfeeding Motivation Scale according to SDT. As predicted, autonomous motivation was positively correlated with maternal well-being and self efficacy, while controlled motivations were positively associated with distress and inversely correlated with self-efficacy. Anxious attachment predicted both controlled and autonomous breastfeeding motivations. DISCUSSION: The findings support the validity of the SDT for breastfeeding motivations, and highlight the role of these motivations as differentiating between positive and negative subjective well-being, among breastfeeding women. PMID- 26372934 TI - Dental attendance among low-income women and their children following a brief motivational counseling intervention: A community randomized trial. AB - This study tested a behavioral intervention to increase dental attendance among rural Oregonian low-income women and their children. It utilized a multi-site, single-blind, randomized trial design. Four hundred women were randomized into one of four conditions to receive prenatal or postpartum motivational interviewing/counseling (MI) or prenatal or postpartum health education (HE). Counselors also functioned as patient navigators. Primary outcomes were dental attendance during pregnancy for the mother and for the child by age 18 months. Attendance was obtained from the Oregon Division of Medical Assistance Programs and participant self-report. Statewide self-reported utilization data were obtained from the Oregon Pregnancy Risk Assessment Monitoring System (PRAMS). Maternal attendance was 92% in the prenatal MI group and 94% in the prenatal HE group (RR = 0.98; 95% CI = 0.93-1.04). Children's attendance was 54% in postpartum MI group and 52% in the postpartum HE group (RR = 1.03; 95% CI = 0.82 1.28). Compared to statewide PRAMS, attendance was higher during pregnancy for study mothers (45% statewide; 95% CI = 40-50%) and for their children by 24 months (36% statewide; 95% CI = 27-44%). MI did not lead to greater attendance when compared to HE alone and cost more to implement. High attendance may be attributable to the counselors' patient navigator function. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01120041. PMID- 26372936 TI - Memory plays tricks on me: perceptual bias induced by memory reactivated size in Ebbinghaus illusion. AB - The relationship between perceptual and memory processing is at the core of cognition. Growing evidence suggests reciprocal influences between them so that memory features should lead to an actual perceptual bias. In the present study, we investigate the reciprocal influence of perceptual and memory processing by further adapting the Ebbinghaus illusion and tested it in a psychophysical design. In a 2AFC (two-alternative forced choice) paradigm, the perceptual bias in the Ebbinghaus illusion was induced by a physical size (Experiment 1) or a memory reactivated size of the inducers (Experiment 2, the size was reactivated thanks to a color-size association). One test disk was presented on the left of the screen and was surrounded by six inducers with a large or small (perceptual or reactivated) size. The test disk varied in size and participants were asked to indicate whether this test disk was smaller or larger than a reference disk presented on the right of the screen (the reference disk was invariant in size). Participants' responses were influenced by the size of the inducers for the perceptual and the reactivated size of the inducers. These results provide new evidence for the influence of memory on perception in a psychophysics paradigm. PMID- 26372937 TI - More mind wandering, fewer original ideas: be not distracted during creative idea generation. AB - Several studies suggest that mind wandering (MW) benefits creativity when the MW occurs in the incubation period of creative problem solving. The aim of present study was to examine the effects of MW that occurs in the course of creative idea generation. Participants received an Alternative Uses Task (AUT) and were asked to generate ideas for 20min. Their MW frequencies as time passed were measured by means of probe-caught MW. Comparisons of the AUT performances of high and low MW groups revealed that greater MW was associated with lower fluency and originality scores on the AUT. Furthermore, the high MW group showed greater MW as time passed, while the low MW group's MW was steady during the course of idea generation. Accordingly, the originality of idea generation decreased with time passing for the high MW group but was steady for the low MW group. The findings suggest that the MW during the course of creative idea generation is negatively related to creativity, perhaps because the control processes involved in idea generation are impaired by the mind wandering. PMID- 26372938 TI - Reversible pure word deafness due to inferior colliculi compression by a pineal germinoma in a young adult. AB - We report a clinical case of a 19-year-old male patient who developed pure word deafness due to the local compressive effect of a pineal germinoma on the inferior colliculi of the quadrigeminal plate. After percutaneous radiation therapy the size of the tumor decreased significantly, while audiometry demonstrated a complete regression of the auditory deficit. Since pure word deafness is commonly attributed to temporal lesions, the inferior colliculi represent an exceptional site for these symptoms. The pathophysiological background and the scarce literature on pure word deafness, especially the one related to neoplasms of the tectal region, are briefly discussed. PMID- 26372939 TI - Multiwall carbon nanotubes increase the microbial community in crude oil contaminated fresh water sediments. AB - Since crude oil contamination is one of the biggest environmental concerns, its removal from contaminated sites is of interest for both researchers and industries. In situ bioremediation is a promising technique for decreasing or even eliminating crude oil and hydrocarbon contamination. However, since these compounds are potentially toxic for many microorganisms, high loads of contamination can inhibit the microbial community and therefore reduce the removal rate. Therefore, any strategy with the ability to increase the microbial population in such circumstances can be of promise in improving the remediation process. In this study, multiwall carbon nanotubes were employed to support microbial growth in sediments contaminated with crude oil. Following spiking of fresh water sediments with different concentrations of crude oil alone and in a mixture with carbon nanotubes for 30days, the microbial profiles in these sediments were obtained using FLX-pyrosequencing. Next, the ratios of each member of the microbial population in these sediments were compared with those values in the untreated control sediment. This study showed that combination of crude oil and carbon nanotubes can increase the diversity of the total microbial population. Furthermore, these treatments could increase the ratios of several microorganisms that are known to be effective in the degradation of hydrocarbons. PMID- 26372940 TI - Reduction of orthophosphates loss in agricultural soil by nano calcium sulfate. AB - Nutrient loss from soil, especially phosphorous (P) from farmlands to natural water bodies via surface runoff or infiltration, have caused significant eutrophication problems. This is because dissolved orthophosphates are usually the limiting nutrient for algal blooms. Currently, available techniques to control eutrophication are surprisingly scarce. Calcium sulfate or gypsum is a common soil amendment and has a strong complexation to orthophosphates. The results showed that calcium sulfate reduced the amount of water extractable P (WEP) through soil incubation tests, suggesting less P loss from farmlands. A greater decrease in WEP occurred with a greater dosage of calcium sulfate. Compared to conventional coarse calcium sulfate, nano calcium sulfate further reduced WEP by providing a much greater specific surface area, higher solubility, better contact with the fertilizer and the soil particles, and superior dispersibility. The enhancement of the nano calcium sulfate for WEP reduction is more apparent for a pellet- than a powdered- fertilizer. At the dosage of Ca/P weight ratio of 2.8, the WEP decreased by 31+/-5% with the nano calcium sulfate compared to 20+/-5% decrease with the coarse calcium sulfate when the pellet fertilizer was used. Computation of the chemical equilibrium speciation shows that calcium hydroxyapatite has the lowest solubility. However, other mineral phases such as hydroxydicalcium phosphate, dicalcium phosphate dihydrate, octacalcium phosphate, and tricalcium phosphate might form preceding to calcium hydroxyapatite. Since calcium sulfate is the major product of the flue gas desulfurization (FGD) process, this study demonstrates a potential beneficial reuse and reduction of the solid FGD waste. PMID- 26372941 TI - DDTs and HCHs in sediment cores from the coastal East China Sea. AB - Four sediment cores were collected along the Yangtze-derived sediment transport pathway in the inner shelf of the East China Sea (ECS) for OCP analysis. The sediment records of HCHs and DDTs in estuarine environment reflected remobilization of chemicals from enhanced soil erosion associated to extreme flood events or large scale land use transformation. The sediment records in the open sea, instead, reflected long-term historical trends of OCP application in the source region. Unlike the so-called mud wedge distribution of sediment, inventories of HCHs and DDTs slightly increased from the mouth of Yangtze River alongshore toward south, suggesting the sediment deposition rate was one of factors on the exposure of chemicals within the inner shelf of the ECS. Re suspension and transport of the Yangtze-derived sediment and consequent fractionation in grain size and TOC were also responsible for the spatial variation of inventories of catchment derived OCPs in a major repository area of the Yangtze suspended sediment. The total burdens of HCHs and DDTs in the inner shelf of the ECS were 35tons and 110tons, respectively. After 1983 (year of the official ban in China), those values were 13tons and 50tons, respectively. It appears that the Yangtze still delivers relatively high inputs of DDTs more than 30years after the official ban. High proportions of DDD+DDE and beta-HCH suggested those OCPs mainly originated from historical usage in the catchment recent years. PMID- 26372942 TI - Removal of enteric viruses and Escherichia coli from municipal treated effluent by zebra mussels. AB - Dreissena polymorpha is a widespread filter-feeder species, resistant to a broad range of environmental conditions and different types of pollutants,which has recently colonized Italian freshwaters. Although widely used to monitor pollution in freshwater environments, this species is also an important food source for some fish and water birds. It can also be used to concentrate or remove particulate organic matter to interrupt avian-to-human transmission of pollutants and control health risks for animals and humans. In this study, the accumulation/inactivation in D. polymorpha of human health-related spiked enteric viruses was described. The removal of endogenous Escherichia coli, the classical indicator of fecal contamination,was tested as well.Our preliminary lab-scale results demonstrate that zebra mussels can reduce significantly poliovirus titer after 24 h and rotavirus titer after 8 h. E. coli counts were also reduced in the presence of zebra mussels by about 1.5 log after 4 h and nearly completely after 24 h. The fate of the two enteric viruses after concentration by zebra mussels was also investigated after mechanical disruption of the tissues. To our knowledge, the accumulation from water and inactivation of human health-related enteric viruses by zebra mussels has never been reported. PMID- 26372943 TI - Improving sustainability in the remediation of contaminated soils by the use of compost and energy valorization by Paulownia fortunei. AB - The plantation of fast growing trees in contaminated sites, in combination with the use of organic wastes, could partially solve a dual environmental problem: the disposal of these wastes and the improvement of soil quality in these degraded soils. This study evaluated the effects of two compost on the quantity and quality of Paulownia fortunei biomass and on syngas production by biomass gasification, produced by plants growing on trace elements contaminated soils. Compost increased biomass production to values similar to those produced in non contaminated soils, due to the improvement in plant nutritional status. Moreover, biomass quality for gasification was increased by compost addition. Trace element accumulation in the biomass was relatively low and not related to biomass production or the gas quality obtained through gasification. Thus, P. fortunei plantations could pose an opportunity to improve the economic balance of the revegetation of contaminated soils, given that other commercial uses such as food or fodder crop production is not recommended in these soils. PMID- 26372944 TI - Vinasse application to sugar cane fields. Effect on the unsaturated zone and groundwater at Valle del Cauca (Colombia). AB - Extensive application of vinasse, a subproduct from sugar cane plantations for bioethanol production, is currently taking place as a source of nutrients that forms part of agricultural management in different agroclimatic regions. Liquid vinasse composition is characterised by high variability of organic compounds and major ions, acid pH (4.7), high TDS concentration (117,416-599,400mgL(-1)) and elevated EC (14,350-64,099MUScm(-1)). A large-scale sugar cane field application is taking place in Valle del Cauca (Colombia), where monitoring of soil, unsaturated zone and the aquifer underneath has been made since 2006 to evaluate possible impacts on three experimental plots. For this assessment, monitoring wells and piezometers were installed to determine groundwater flow and water samples were collected for chemical analysis. In the unsaturated zone, tensiometers were installed at different depths to determine flow patterns, while suction lysimeters were used for water sample chemical determinations. The findings show that in the sandy loam plot (Hacienda Real), the unsaturated zone is characterised by low water retention, showing a high transport capacity, while the other two plots of silty composition presented temporal saturation due to La Nina event (2010-2011). The strong La Nina effect on aquifer recharge which would dilute the infiltrated water during the monitoring period and, on the other hand dissolution of possible precipitated salts bringing them back into solution may occur. A slight increase in the concentration of major ions was observed in groundwater (~5% of TDS), which can be attributed to a combination of factors: vinasse dilution produced by water input and hydrochemical processes along with nutrient removal produced by sugar cane uptake. This fact may make the aquifer vulnerable to contamination. PMID- 26372945 TI - Infant outcomes following treatment of antenatal depression: Findings from a pilot randomized controlled trial. AB - INTRODUCTION: Maternal antenatal depression is associated with an increased risk of emotional and behavioural problems in children. More recently antenatal depression has been associated with shorter sleep duration, higher number of awakenings and sleep problems in infants. Examining the effect of treatment of depression on child development is the next step in unravelling the complex association between antenatal depression and offspring development. METHODS: We used data from a pilot RCT of women with antenatal depression who received either Cognitive Behavioural Therapy (CBT) or Treatment as Usual (TAU), to examine infant sleep duration and temperament two months postpartum. Data was available for n=14 in the CBT group and n=11 in the TAU group. RESULTS: No differences by treatment arm were evident. Improvement in depression scores during pregnancy was associated with easier temperament (beta=-.45, p=.024) and shorter nocturnal sleep duration (beta=-.58, p=.003). The findings were more pronounced in the CBT group compared to the TAU group. LIMITATIONS: This was a pilot RCT and as such the sample size was small and there was some loss to follow up between the baseline and postnatal assessment. CONCLUSION: Improvement in antenatal depressive symptoms may have beneficial effects for the infant; whether these are directly through effects on foetal development or indirectly through changes in the postnatal mother-infant relationship remains to be determined. PMID- 26372946 TI - Overexpression of a tomato flavanone 3-hydroxylase-like protein gene improves chilling tolerance in tobacco. AB - Flavonoids are secondary metabolites found in plants with a wide range of biological functions, such as stress protection. This study investigated the functions of a tomato (Solanum lycopersicum) flavanone 3-hydroxylase-like protein gene SlF3HL by using transgenic tobacco. The expression of the gene was up regulated under chilling (4 degrees C), heat (42 degrees C), salt (NaCl) and oxidative (H2O2) stresses. The transgenic plants that displayed high SlF3HL mRNA and protein levels showed higher flavonoid content than the WT plants. Moreover, the expression of three flavonoid biosynthesis-related structural genes, namely, chalcone synthase (CHS), chalcone isomerase (CHI) and flavonol synthase (FLS) was also higher in the transgenic plants than in the WT plants. Under chilling stress, the transgenic plants showed not only faster seed germination, better survival and growth, but also lower malondialdehyde (MDA) accumulation, relative electrical conductivity (REC) and H2O2 and O2(.-) levels compared with WT plants. These results suggested that SlF3HL stimulated flavonoid biosynthesis in response to chilling stress. PMID- 26372947 TI - Quantitative determination of dopamine in human plasma by a highly sensitive LC MS/MS assay: Application in preterm neonates. AB - The determination of dopamine facilitates better understanding of the complex brain disorders in the central nervous system and the regulation of endocrine system, cardiovascular functions and renal functions in the periphery. The purpose of this study was to develop a highly sensitive and reliable assay for the quantification of dopamine in human neonate plasma. Dopamine was extracted from human plasma by strong cation exchange (SCX) solid phase extraction (SPE), and subsequently derivatized with propionic anhydride. The derivatized analyte was separated by a Waters Acquity UPLC BEH C18 column using gradient elution at 0.4 ml/min with mobile phases A (0.2% formic acid in water [v/v]) and B (MeOH-ACN [v/v, 30:70]). Analysis was performed under positive electrospray ionization tandem mass spectrometer (ESI-MS/MS) in the multiple reaction monitoring (MRM) mode. The stable and relatively non-polar nature of the derivatized analyte enables reliable quantification of dopamine in the range of 10-1000 pg/ml using 200 MUl of plasma sample. The method was validated with intra-day and inter-day precision less than 7%, and the intra-day and inter-day accuracy of 91.9-101.9% and 92.3-102.6%, respectively. The validated assay was applied to quantify dopamine levels in two preterm neonate plasma samples. In conclusion, a sensitive and selective LC-MS/MS method has been developed and validated, and successfully used for the determination of plasma dopamine levels in preterm neonates. PMID- 26372949 TI - New Advances in the Treatment of Metastatic Pancreatic Cancer. AB - BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is characterised by an extremely poor overall survival (OS) compared to other solid tumours. As the incidence of the disease is rising and the treatment options are limited, PDAC is projected to be the 2nd leading cause of cancer-related deaths in the United States by 2030. A majority of patients are not eligible for curative resection at the time of diagnosis, and those that are resected will often relapse within the first few years after surgery. SUMMARY: Until recently, the nucleoside analogue gemcitabine has been the standard of care for patients with non-resectable PDAC with only marginal effects on OS. In 2011, the gemcitabine-free FOLFIRINOX regimen (folinic acid, fluorouracil, irinotecan and oxaliplatin) showed a significant survival advantage for patients with metastatic PDAC in a phase III trial. In 2013, the Metastatic Pancreatic Adenocarcinoma Trial phase III trial with nano- formulated albumin-bound paclitaxel (nab-paclitaxel) in combination with gemcitabine also resulted in a significant survival extension compared to gemcitabine monotherapy. However, both intensified therapy regimens show a broad spectrum of side effects and patients need to be carefully selected for the most appropriate protocol. KEY MESSAGE: In this study, recent advances in the chemotherapeutic options available to treat metastatic PDAC and their implications for today's treatment choices are reviewed. PMID- 26372948 TI - Comprehensive analysis of cancer-associated somatic mutations in class I HLA genes. AB - Detection of somatic mutations in human leukocyte antigen (HLA) genes using whole exome sequencing (WES) is hampered by the high polymorphism of the HLA loci, which prevents alignment of sequencing reads to the human reference genome. We describe a computational pipeline that enables accurate inference of germline alleles of class I HLA-A, B and C genes and subsequent detection of mutations in these genes using the inferred alleles as a reference. Analysis of WES data from 7,930 pairs of tumor and healthy tissue from the same patient revealed 298 nonsilent HLA mutations in tumors from 266 patients. These 298 mutations are enriched for likely functional mutations, including putative loss-of-function events. Recurrence of mutations suggested that these 'hotspot' sites were positively selected. Cancers with recurrent somatic HLA mutations were associated with upregulation of signatures of cytolytic activity characteristic of tumor infiltration by effector lymphocytes, supporting immune evasion by altered HLA function as a contributory mechanism in cancer. PMID- 26372950 TI - Remyelination after Lysophosphatidyl Choline-Induced Demyelination Is Stimulated by Bone Marrow Stromal Cell-Derived Oligoprogenitor Cell Transplantation. AB - Bone marrow stromal cells (BMSCs) are a desirable cell source that may be useful for the treatment of neurodegenerative diseases given their capacity to differentiate into various types of cells. The current study aimed to investigate whether oligoprogenitor cell (OPC)-derived BMSCs have therapeutic benefits in an animal model of local demyelination. BMSCs were transdifferentiated into OPCs using a defined culture medium supplemented with a combination of inducers. The differentiation capacity of the BMSCs was evaluated at the end of the induction phase by assessing the expression levels of the glial-specific markers oligodendrocyte transcription factor 2 and O4 surface antigen. Local demyelination was induced in the corpus callosum of adult female rats via direct injection of lysophosphatidylcholine (LPC) followed by engraftment of BMSC generated OPCs. The rats were divided into sham control, vehicle control, and cell-transplanted groups. The changes in the extent of demyelination and the robustness of the remyelination event were assessed using Luxol Fast Blue staining and immunohistochemical analysis 1 week after LPC injection and 2 weeks after cell transplantation. Consequently, transplantation of OPCs into the demyelinated corpus callosum model resulted in differentiation of the cells into mature oligodendrocytes that were immunopositive for myelin basic protein. Furthermore, OPC transplantation mitigated demyelination and augmented remyelination relative to controls. These findings suggest that BMSC-derived OPCs can be utilized in therapeutic approaches for the management of demyelination associated diseases such as multiple sclerosis. PMID- 26372951 TI - The Self in Psychopathology. PMID- 26372952 TI - Metformin Protects Auditory Hair Cells from Gentamicin-Induced Toxicity in vitro. AB - Metformin is a commonly used antidiabetic drug. It has been shown that this drug activates the AMP-activated protein kinase, which inhibits downstream the mammalian target of rapamycin. In addition, several studies indicate that metformin reduces intracellular reactive oxygen species. Our data, using an in vitro rat model, indicate that metformin is able to protect auditory hair cells (HCs) from gentamicin-induced apoptotic cell death. Moreover, metformin has no toxic effect on spiral ganglion neuronal survival or outgrowth in vitro. These results suggest a protective effect of metformin on auditory HC survival in gentamicin-induced HC loss in vitro. PMID- 26372953 TI - Allostery vs. "allokairy". PMID- 26372954 TI - Long-term litter decomposition controlled by manganese redox cycling. AB - Litter decomposition is a keystone ecosystem process impacting nutrient cycling and productivity, soil properties, and the terrestrial carbon (C) balance, but the factors regulating decomposition rate are still poorly understood. Traditional models assume that the rate is controlled by litter quality, relying on parameters such as lignin content as predictors. However, a strong correlation has been observed between the manganese (Mn) content of litter and decomposition rates across a variety of forest ecosystems. Here, we show that long-term litter decomposition in forest ecosystems is tightly coupled to Mn redox cycling. Over 7 years of litter decomposition, microbial transformation of litter was paralleled by variations in Mn oxidation state and concentration. A detailed chemical imaging analysis of the litter revealed that fungi recruit and redistribute unreactive Mn(2+) provided by fresh plant litter to produce oxidative Mn(3+) species at sites of active decay, with Mn eventually accumulating as insoluble Mn(3+/4+) oxides. Formation of reactive Mn(3+) species coincided with the generation of aromatic oxidation products, providing direct proof of the previously posited role of Mn(3+)-based oxidizers in the breakdown of litter. Our results suggest that the litter-decomposing machinery at our coniferous forest site depends on the ability of plants and microbes to supply, accumulate, and regenerate short-lived Mn(3+) species in the litter layer. This observation indicates that biogeochemical constraints on bioavailability, mobility, and reactivity of Mn in the plant-soil system may have a profound impact on litter decomposition rates. PMID- 26372955 TI - Suburbanization, estrogen contamination, and sex ratio in wild amphibian populations. AB - Research on endocrine disruption in frog populations, such as shifts in sex ratios and feminization of males, has predominantly focused on agricultural pesticides. Recent evidence suggests that suburban landscapes harbor amphibian populations exhibiting similar levels of endocrine disruption; however the endocrine disrupting chemical (EDC) sources are unknown. Here, we show that sex ratios of metamorphosing frogs become increasingly female-dominated along a suburbanization gradient. We further show that suburban ponds are frequently contaminated by the classical estrogen estrone and a variety of EDCs produced by plants (phytoestrogens), and that the diversity of organic EDCs is correlated with the extent of developed land use and cultivated lawn and gardens around a pond. Our work also raises the possibility that trace-element contamination associated with human land use around suburban ponds may be contributing to the estrogenic load within suburban freshwaters and constitutes another source of estrogenic exposure for wildlife. These data suggest novel, unexplored pathways of EDC contamination in human-altered environments. In particular, we propose that vegetation changes associated with suburban neighborhoods (e.g., from forests to lawns and ornamental plants) increase the distribution of phytoestrogens in surface waters. The result of frog sex ratios varying as a function of human land use implicates a role for environmental modulation of sexual differentiation in amphibians, which are assumed to only have genetic sex determination. Overall, we show that endocrine disruption is widespread in suburban frog populations and that the causes are likely diverse. PMID- 26372956 TI - Caspase 3 cleavage of Pax7 inhibits self-renewal of satellite cells. AB - Compensatory growth and regeneration of skeletal muscle is dependent on the resident stem cell population, satellite cells (SCs). Self-renewal and maintenance of the SC niche is coordinated by the paired-box transcription factor Pax7, and yet continued expression of this protein inhibits the myoblast differentiation program. As such, the reduction or removal of Pax7 may denote a key prerequisite for SCs to abandon self-renewal and acquire differentiation competence. Here, we identify caspase 3 cleavage inactivation of Pax7 as a crucial step for terminating the self-renewal process. Inhibition of caspase 3 results in elevated Pax7 protein and SC self-renewal, whereas caspase activation leads to Pax7 cleavage and initiation of the myogenic differentiation program. Moreover, in vivo inhibition of caspase 3 activity leads to a profound disruption in skeletal muscle regeneration with an accumulation of SCs within the niche. We have also noted that casein kinase 2 (CK2)-directed phosphorylation of Pax7 attenuates caspase-directed cleavage. Together, these results demonstrate that SC fate is dependent on opposing posttranslational modifications of the Pax7 protein. PMID- 26372957 TI - Single quantum dot controls a plasmonic cavity's scattering and anisotropy. AB - Plasmonic cavities represent a promising platform for controlling light-matter interaction due to their exceptionally small mode volume and high density of photonic states. Using plasmonic cavities for enhancing light's coupling to individual two-level systems, such as single semiconductor quantum dots (QD), is particularly desirable for exploring cavity quantum electrodynamic (QED) effects and using them in quantum information applications. The lack of experimental progress in this area is in part due to the difficulty of precisely placing a QD within nanometers of the plasmonic cavity. Here, we study the simplest plasmonic cavity in the form of a spherical metallic nanoparticle (MNP). By controllably positioning a semiconductor QD in the close proximity of the MNP cavity via atomic force microscope (AFM) manipulation, the scattering spectrum of the MNP is dramatically modified due to Fano interference between the classical plasmonic resonance of the MNP and the quantized exciton resonance in the QD. Moreover, our experiment demonstrates that a single two-level system can render a spherical MNP strongly anisotropic. These findings represent an important step toward realizing quantum plasmonic devices. PMID- 26372958 TI - Tandem catalysis for the production of alkyl lactates from ketohexoses at moderate temperatures. AB - Retro-aldol reactions have been implicated as the limiting steps in catalytic routes to convert biomass-derived hexoses and pentoses into valuable C2, C3, and C4 products such as glycolic acid, lactic acid, 2-hydroxy-3-butenoic acid, 2,4 dihydroxybutanoic acid, and alkyl esters thereof. Due to a lack of efficient retro-aldol catalysts, most previous investigations of catalytic pathways involving these reactions were conducted at high temperatures (>=160 degrees C). Here, we report moderate-temperature (around 100 degrees C) retro-aldol reactions of various hexoses in aqueous and alcoholic media with catalysts traditionally known for their capacity to catalyze 1,2-intramolecular carbon shift (1,2-CS) reactions of aldoses, i.e., various molybdenum oxide and molybdate species, nickel(II) diamine complexes, alkali-exchanged stannosilicate molecular sieves, and amorphous TiO2-SiO2 coprecipitates. Solid Lewis acid cocatalysts that are known to catalyze 1,2-intramolecular hydride shift (1,2-HS) reactions that enable the formation of alpha-hydroxy carboxylic acids from tetroses, trioses, and glycolaldehyde, but cannot readily catalyze retro-aldol reactions of hexoses and pentoses at these moderate temperatures, are shown to be compatible with the aforementioned retro-aldol catalysts. The combination of a distinct retro-aldol catalyst with a 1,2-HS catalyst enables lactic acid and alkyl lactate formation from ketohexoses at moderate temperatures (around 100 degrees C), with yields comparable to best-reported chemocatalytic examples at high temperature conditions (>=160 degrees C). The use of moderate temperatures enables numerous desirable features such as lower pressure and significantly less catalyst deactivation. PMID- 26372959 TI - A mechanically driven form of Kirigami as a route to 3D mesostructures in micro/nanomembranes. AB - Assembly of 3D micro/nanostructures in advanced functional materials has important implications across broad areas of technology. Existing approaches are compatible, however, only with narrow classes of materials and/or 3D geometries. This paper introduces ideas for a form of Kirigami that allows precise, mechanically driven assembly of 3D mesostructures of diverse materials from 2D micro/nanomembranes with strategically designed geometries and patterns of cuts. Theoretical and experimental studies demonstrate applicability of the methods across length scales from macro to nano, in materials ranging from monocrystalline silicon to plastic, with levels of topographical complexity that significantly exceed those that can be achieved using other approaches. A broad set of examples includes 3D silicon mesostructures and hybrid nanomembrane nanoribbon systems, including heterogeneous combinations with polymers and metals, with critical dimensions that range from 100 nm to 30 mm. A 3D mechanically tunable optical transmission window provides an application example of this Kirigami process, enabled by theoretically guided design. PMID- 26372960 TI - Mercury offloaded in Northern elephant seal hair affects coastal seawater surrounding rookery. AB - Methylmercury (MeHg) is a potent neurotoxin that is biomagnified approximately 1 10 million-fold in aquatic carnivores such as the Northern elephant seal (Mirounga angustirostris), whose excreta and molted pelage, in turn, constitute a source of environmental MeHg contamination at the base of marine food chains. The potential for this top-down contamination is greatest in coastal areas with productive marine ecosystems that provide ideal habitats for large marine mammal colonies that can number in the thousands. This recycling of MeHg was evidenced by comparing total mercury (HgT) and MeHg concentrations in seawater, and HgT in molted pelage of M. angustirostris, at the Ano Nuevo State Reserve pinniped rookery with concentrations at neighboring coastal sites in Central California. Seawater MeHg concentrations around the rookery (average = 2.5 pM) were markedly higher than those at the comparison coastal sites (average = 0.30 pM), and were as high as 9.5 pM during the M. angustirostris molting season. As a consequence, excreta and molts from this marine mammal colony, and presumably other marine predator populations, constitute a major source of MeHg at the base of the local marine food chain. PMID- 26372961 TI - Widespread convergence in toxin resistance by predictable molecular evolution. AB - The question about whether evolution is unpredictable and stochastic or intermittently constrained along predictable pathways is the subject of a fundamental debate in biology, in which understanding convergent evolution plays a central role. At the molecular level, documented examples of convergence are rare and limited to occurring within specific taxonomic groups. Here we provide evidence of constrained convergent molecular evolution across the metazoan tree of life. We show that resistance to toxic cardiac glycosides produced by plants and bufonid toads is mediated by similar molecular changes to the sodium potassium-pump (Na(+)/K(+)-ATPase) in insects, amphibians, reptiles, and mammals. In toad-feeding reptiles, resistance is conferred by two point mutations that have evolved convergently on four occasions, whereas evidence of a molecular reversal back to the susceptible state in varanid lizards migrating to toad-free areas suggests that toxin resistance is maladaptive in the absence of selection. Importantly, resistance in all taxa is mediated by replacements of 2 of the 12 amino acids comprising the Na(+)/K(+)-ATPase H1-H2 extracellular domain that constitutes a core part of the cardiac glycoside binding site. We provide mechanistic insight into the basis of resistance by showing that these alterations perturb the interaction between the cardiac glycoside bufalin and the Na(+)/K(+)-ATPase. Thus, similar selection pressures have resulted in convergent evolution of the same molecular solution across the breadth of the animal kingdom, demonstrating how a scarcity of possible solutions to a selective challenge can lead to highly predictable evolutionary responses. PMID- 26372962 TI - Structural insight into selectivity and resistance profiles of ROS1 tyrosine kinase inhibitors. AB - Oncogenic ROS1 fusion proteins are molecular drivers in multiple malignancies, including a subset of non-small cell lung cancer (NSCLC). The phylogenetic proximity of the ROS1 and anaplastic lymphoma kinase (ALK) catalytic domains led to the clinical repurposing of the Food and Drug Administration (FDA)-approved ALK inhibitor crizotinib as a ROS1 inhibitor. Despite the antitumor activity of crizotinib observed in both ROS1- and ALK-rearranged NSCLC patients, resistance due to acquisition of ROS1 or ALK kinase domain mutations has been observed clinically, spurring the development of second-generation inhibitors. Here, we profile the sensitivity and selectivity of seven ROS1 and/or ALK inhibitors at various levels of clinical development. In contrast to crizotinib's dual ROS1/ALK activity, cabozantinib (XL-184) and its structural analog foretinib (XL-880) demonstrate a striking selectivity for ROS1 over ALK. Molecular dynamics simulation studies reveal structural features that distinguish the ROS1 and ALK kinase domains and contribute to differences in binding site and kinase selectivity of the inhibitors tested. Cell-based resistance profiling studies demonstrate that the ROS1-selective inhibitors retain efficacy against the recently reported CD74-ROS1(G2032R) mutant whereas the dual ROS1/ALK inhibitors are ineffective. Taken together, inhibitor profiling and stringent characterization of the structure-function differences between the ROS1 and ALK kinase domains will facilitate future rational drug design for ROS1- and ALK driven NSCLC and other malignancies. PMID- 26372963 TI - Design and structure of two HIV-1 clade C SOSIP.664 trimers that increase the arsenal of native-like Env immunogens. AB - A key challenge in the quest toward an HIV-1 vaccine is design of immunogens that can generate a broadly neutralizing antibody (bnAb) response against the enormous sequence diversity of the HIV-1 envelope glycoprotein (Env). We previously demonstrated that a recombinant, soluble, fully cleaved SOSIP.664 trimer based on the clade A BG505 sequence is a faithful antigenic and structural mimic of the native trimer in its prefusion conformation. Here, we sought clade C native-like trimers with comparable properties. We identified DU422 and ZM197M SOSIP.664 trimers as being appropriately thermostable (Tm of 63.4 degrees C and 62.7 degrees C, respectively) and predominantly native-like, as determined by negative stain electron microscopy (EM). Size exclusion chromatography, ELISA, and surface plasmon resonance further showed that these trimers properly display epitopes for all of the major bnAb classes, including quaternary-dependent, trimer-apex (e.g., PGT145) and gp120/gp41 interface (e.g., PGT151) epitopes. A cryo-EM reconstruction of the ZM197M SOSIP.664 trimer complexed with VRC01 Fab against the CD4 binding site at subnanometer resolution revealed a striking overall similarity to its BG505 counterpart with expected local conformational differences in the gp120 V1, V2, and V4 loops. These stable clade C trimers contribute additional diversity to the pool of native-like Env immunogens as key components of strategies to induce bnAbs to HIV-1. PMID- 26372965 TI - Ritual drinks in the pre-Hispanic US Southwest and Mexican Northwest. AB - Chemical analyses of organic residues in fragments of pottery from 18 sites in the US Southwest and Mexican Northwest reveal combinations of methylxanthines (caffeine, theobromine, and theophylline) indicative of stimulant drinks, probably concocted using either cacao or holly leaves and twigs. The results cover a time period from around A.D. 750-1400, and a spatial distribution from southern Colorado to northern Chihuahua. As with populations located throughout much of North and South America, groups in the US Southwest and Mexican Northwest likely consumed stimulant drinks in communal, ritual gatherings. The results have implications for economic and social relations among North American populations. PMID- 26372964 TI - Phospholipid dysregulation contributes to ApoE4-associated cognitive deficits in Alzheimer's disease pathogenesis. AB - The apolipoprotein E4 (ApoE4) allele is the strongest genetic risk factor for developing sporadic Alzheimer's disease (AD). However, the mechanisms underlying the pathogenic nature of ApoE4 are not well understood. In this study, we have found that ApoE proteins are critical determinants of brain phospholipid homeostasis and that the ApoE4 isoform is dysfunctional in this process. We have found that the levels of phosphoinositol biphosphate (PIP2) are reduced in postmortem human brain tissues of ApoE4 carriers, in the brains of ApoE4 knock-in (KI) mice, and in primary neurons expressing ApoE4 alleles compared with those levels in ApoE3 counterparts. These changes are secondary to increased expression of a PIP2-degrading enzyme, the phosphoinositol phosphatase synaptojanin 1 (synj1), in ApoE4 carriers. Genetic reduction of synj1 in ApoE4 KI mouse models restores PIP2 levels and, more important, rescues AD-related cognitive deficits in these mice. Further studies indicate that ApoE4 behaves similar to ApoE null conditions, which fails to degrade synj1 mRNA efficiently, unlike ApoE3 does. These data suggest a loss of function of ApoE4 genotype. Together, our data uncover a previously unidentified mechanism that links ApoE4-induced phospholipid changes to the pathogenic nature of ApoE4 in AD. PMID- 26372967 TI - Patient death in simulation-based medical education. PMID- 26372968 TI - Medicaid Moving Forward. PMID- 26372966 TI - NMR structure and dynamics of the agonist dynorphin peptide bound to the human kappa opioid receptor. AB - The structure of the dynorphin (1-13) peptide (dynorphin) bound to the human kappa opioid receptor (KOR) has been determined by liquid-state NMR spectroscopy. (1)H and (15)N chemical shift variations indicated that free and bound peptide is in fast exchange in solutions containing 1 mM dynorphin and 0.01 mM KOR. Radioligand binding indicated an intermediate-affinity interaction, with a Kd of ~200 nM. Transferred nuclear Overhauser enhancement spectroscopy was used to determine the structure of bound dynorphin. The N-terminal opioid signature, YGGF, was observed to be flexibly disordered, the central part of the peptide from L5 to R9 to form a helical turn, and the C-terminal segment from P10 to K13 to be flexibly disordered in this intermediate-affinity bound state. Combining molecular modeling with NMR provided an initial framework for understanding multistep activation of a G protein-coupled receptor by its cognate peptide ligand. PMID- 26372969 TI - Learning how health care works. PMID- 26372970 TI - Comparing Individual Health Coverage On and Off the Affordable Care Act's Insurance Exchanges. AB - The new health insurance exchanges are the core of the Affordable Care Act's (ACA) reforms, but how the law improves the nonsubsidized portion of the individual market is also important. This issue brief compares products sold on and off the exchanges to gain insight into how the ACA's market reforms are functioning. Initial concerns that insurers might seek to enroll lower-risk customers outside the exchanges have not been realized. Instead, more-generous benefit plans, which appeal to people with health problems, constitute a greater portion of plans sold off-exchange than those sold on-exchange. Although insur ers that sell mostly on the exchanges incur an additional fee, they still devote a greater portion of their premium dollars to medical care. Their projected admin istrative costs and profit margins are lower than are those of insurers selling only off the exchanges. PMID- 26372971 TI - Competition Among Medicare's Private Health Plans: Does It Really Exist? AB - Competition among private Medicare Advantage (MA) plans is seen by some as leading to lower premiums and expanded benefits. But how much competition exists in MA markets? Using a standard measure of market competition, our analysis finds that 97 percent of markets in U.S. counties are highly concentrated and therefore lacking in significant MA plan competition. Competition is considerably lower in rural counties than in urban ones. Even among the 100 counties with the greatest numbers of Medicare beneficiaries, 81 percent do not have competitive MA markets. Market power is concentrated among three nationwide insurance organizations in nearly two-thirds of those 100 counties. PMID- 26372972 TI - How Strong Is the Primary Care Safety Net? Assessing the Ability of Federally Qualified Health Centers to Serve as Patient-Centered Medical Homes. AB - By expanding access to affordable insurance coverage for millions of Americans, the Affordable Care Act will likely increase demand for the services provided by federally qualified health centers (FQHCs), which provide an important source of care in low-income communities. A pair of Commonwealth Fund surveys asked health center leaders about their ability to function as medical homes. Survey findings show that between 2009 and 2013, the percentage of centers exhibiting medium or high levels of medical home capability almost doubled, from 32 percent to 62 percent. The greatest improvement was reported in patient tracking and care management. Despite this increased capability, health centers reported diminished ability to coordinate care with providers outside of the practice, particularly specialists. Ongoing federal funding and technical support for medical home transformation will be needed to ensure that FQHCs can fulfill their mission of providing high-quality, comprehensive care to low-income and minority populations. PMID- 26372973 TI - [The use of rituximab in rheumatoid arthritis: about 55 patients]. AB - INTRODUCTION: The use of rituximab in rheumatoid arthritis (RA) has shown good efficiency and also well tolerated in randomized trials. The aim of our study was to evaluate in the " real life " the efficacy of rituximab in the treatment of RA, to identify predictors of response to rituximab and to assess tolerance. MATERIALS AND METHODS: A retrospective observational study in patients with rheumatoid arthritis was made. A bivariate analysis and a logistic regression were used to identify factors associated with the response at 6 months. RESULTS: The EULAR response to rituximab in the treatment of RA was 77.4 % at 3 months and 83 % at 6 months. The evolution of DAS28 at 3 months and 6 months were statistically significant (P < 0.001). The response to the treatment was associated with rheumatoid factor (RF) (P = 0,001), anti-CCP positivity (P = 0,001) and a significant disease activity (P = 0,013). Other factors (age, sex, HAQ, disease duration of RA, MTX associated corticosteroid partner) are not associated with the presence of a EULAR response rituximab. After logistic regression, there persisted an association with disease activity (OR 7.672; 95% CI 1.39-42.11; P = 0.019) and rheumatoid factor positivity (OR 7.91 ; CI 1.64 38.11; P = 0.010). We found a good tolerance in 82% of the patients. CONCLUSION: Our study shows efficacy of rituximab in a polyarthritis Moroccan population and a good tolerance. An important activity (high DAS28) and RF positivity appeared to be associated with increased response to rituximab. PMID- 26372974 TI - [Delivery by midwife in full autonomy. Literature review and analysis of 80 months of activity at the University Hospital Erasme]. AB - INTRODUCTION: The last century focused all its attention on the care of the pathological pregnancies with remarkable results, at the price of fatal overmedicalisation in normal pregnancies. Efforts centered on the pregnant patients at low risk are being developped. OBJECTIVES: To compare obstetric and neonatal outcomes obtained by independent midwives (IM) to a group control of pregnant women at low risk at Hospital Erasme. MATERIAL AND METHODS: Retrospective constitution of a multivariated cohort case-witnesses 1:2 of patients at low risk including 128 followed in antenatal and delivered by the IM and 256 followed in antenatal and delivered by the group control Erasme (E) RESULTS: The rate of spontaneous vaginal delivery is significantly higher in the group IM (88,28 % versus 77,7 % in the group E). The rates of epidurals (66,79 % versus 37,50 %) and episiotomies (24,61 % versus 8,60 %) are significantly higher in the group E. Transfers to the neonatal unit are more frequent in the group E. CONCLUSION: The obstetrics attitudes are less interventionist in the IM group. The reasons can be linked to bias selection or to different obstetrics practices in both groups. Positive effects in terms of maternal and neonatal outcomes are quite positive. PMID- 26372975 TI - [Evolution of low back pain after bariatric surgery]. AB - Although frequently called to mind by physicians, the relationship between overweight and low back pain is poorly understood and remains controversial. The present study aims to evaluate the evolution of low back pain in 65 patients planned for a bariatric surgery. The patients were enrolled prospectively. 54 patients (80%) could be evaluated 5 months after the procedure, and 47 patients (72%) were evaluated 22 months after surgery. Mean weight loss was 19 +/- 9 kg (P < 0.001) at 22 months post-op. Patients demonstrated a statistically significant improvement of the NRS, Oswestry and SF-36 scores. This study suggests that low back pain might be reduced following bariatric surgery. However, the lack of dose response effect is against a causal relationship between low back pain and obesity. Larger randomised controls are needed to determine a causal relationship. PMID- 26372976 TI - [Munchausen by proxy syndrome]. AB - The Munchausen syndrome by proxy (MSBP) was first described in 1977 by the English paediatrician Roy Meadow. The MSBP is an extremely complicated diagnosis because of the difficulty in finding the incriminating evidence of its existence and because of the ethical issue it raises for caregivers. Its implications from a medical, psychological and legal point of view raise difficult questions for any professional confronted to it. In this article we will first present the case of a 16-year-old teenager who had been bedridden in hospital for a year, before an atypical form of MSBP was finally diagnosed, after a stay in a child and adolescent psychiatry unit. We will then discuss this case in light of a literature review on the MSBP. PMID- 26372977 TI - [Interest of non invasive navigation in total knee arthroplasty]. AB - During surgery of total knee arthroplasty, we use a computerized non invasive navigation (Brainlab Victor Vision CT-free) to assess the accuracy of the bone cuts (navigation expresse). The purpose of this study is to evaluate non invasive navigation when a total knee arthroplasty is achieved by conventional instrumentation. The study is based on forty total knee arthroplasties. The accuracy of the tibial and distal femoral bone cuts, checked by non invasive navigation, is evaluated prospectively. In our clinical series, we have obtained, with the conventional instrumentation, a correction of the mechanical axis only in 90 % of cases (N = 36). With non invasive navigation, we improved the positioning of implants and obtained in all cases the desired axiometry in the frontal plane. Although operative time is increased by about 15 minutes, the non invasive navigation does not induce intraoperative or immediate postoperative complications. Despite the cost of this technology, we believe that the reliability of the procedure is enhanced by a simple and reproducible technique. PMID- 26372978 TI - [Sports-related concussions: are we (fully) aware of the consequences?]. AB - Contact sports and sports with high risk of head traumatism are increasingly becoming more popular. This trend leads to a 60% increase of sport-related concussions in the decade. It is therefore important to summarize the current knowledge in this field (diagnosis, risk factors...) in order to help clinicians to improve this pathology management. Short and long term consequences are too often minimized by clinicians, while related clinical disorders should not be neglected (e.g. headaches, cognitive troubles, vestibular troubles, depression...). Complications risks are directly linked to the number of concussions or if patients return to play before complete recovery. Correct knowledge of symptoms and of the various assessment tests are consequently therefore important to know in order identity and tackle long term complications of sport-related concussions. PMID- 26372979 TI - [Anti-NEP and anti-PLA2R antibodies in membranous nephropathy: an update]. AB - Membranous nephropathy (MN) is the most common cause for nephrotic syndrome in adults and occurs as an idiopathic (primary) or secondary disease. Since the early 2000's, substantial advances have been made in the understanding of the molecular bases of MN. The neutral endopeptidase (NEP) and the receptor for secretory phospholipase A2 (PLA2R) have been identified as target antigens for circulating and deposited antibodies in allo-immune neonatal and adult " idiopathic " MN, respectively. These antibodies recognize specific antigens of podocytes, precipitate as subepithelial immune complexes and activate complement leading to proteinuria. Anti-PLA2R antibodies are of particular clinical importance. Indeed, they are detected in approximately 70% of primary MN in adults, demonstrating that MN actually is an autoimmune condition specific to the kidney. In Europeans, genome-wide studies have shown an association between alleles of PLA2R1 and HLA DQA1 (class II genes of tissue histocompatibility complex) genes and idiopathic MN. Newly developed diagnostic tests detecting circulating anti-PLA2R antibody and PLA2R antigen in glomerular deposits have induced a change in paradigm in the diagnostic approach of idiopathic MN. Measurement of circulating anti-PLA2R antibody is also very useful for the monitoring of MN activity. However, the mechanisms responsible for the formation of anti-PLA2R antibodies as well as those involved in the progression of MN to end-stage renal disease remain to be defined. PMID- 26372980 TI - [Recurrent episodes of brushite nephrolithiasis revealing primary hyperparathyroidism]. AB - INTRODUCTION: Nephrolithiasis is a frequent disease observed in 1 to 20 % of the general population. This disease predominates in male patients (2:1) and is characterized by a high rate of recurrences (about 50 %). CASE REPORT: We report the case of a 45-year old male patient who experienced during about ten years recurrent bilateral renal colic episodes due to brushite lithiasis. These stones were treated with multiple extracorporeal shock wave lithotripsy sessions. A pyeloureteral junction syndrome predisposing to bulky stones formation has been put in evidence and required a pyeloplasty. After more than ten years of disease activity, a biochemical screening diagnosed primary hyperparathyroidism (PHPT). Radiological assessment identified a parathyroid gland adenoma. Successful surgical removal of this lesion was followed by resolution of the symptomatic kidney stones formation. DISCUSSION: PHPT is associated with kidney stones in about 20 % of the patients. Hypercalciuria is the main risk factor of stones formation but other predisposing factors are also probably involved. Patients carrying a polymorphism located in the coding sequence of the calcium-sensing receptor gene or in the regulatory region of this gene seem to experience an increased occurrence of urinary lithiasis. CONCLUSION: The present case stresses the importance of a metabolic assessment in all patients with recurrent nephrolithiasis, especially in case of bilateral episodes. PMID- 26372981 TI - [A 74-year old woman with orofacial granulomatosis]. AB - INTRODUCTION: Orofacial granulomatosis represents a group of pathologies characterized by a granulomatous inflammation of the face and the oral mucosa. Its etiology is unknown. Since the macrocheilitis resulting from an inflammation could be associated to different pathologies, an accurate diagnosis has to be established. OBSERVATION: A 74-year old woman developed a swelling of the inferior lip spreading towards the chin. No lesions was present on the oral mucosa. No other symptoms were reported. The biopsy and further exams concluded to an idiopathic orofacial granulomatosis. Triamcinolone 10 mg/ml was used as treatment and has allowed a lasting improvement of the swelling. DISCUSSION: This rare observation, especially with an older patient, has allowed to illustrate the importance of an accurate diagnosis when facing a macrocheilitis. Indeed, macrocheilitis can be associated to pathologies such as Crohn disease, sarcoidosis or tuberculosis, requiring an appropriate care. PMID- 26372982 TI - [Suffering, cruel load on animals and humans (second part) ]. PMID- 26372983 TI - [Homage to Professor Philippe Lheureux]. PMID- 26372984 TI - [Homage to Professor Andre Govaerts]. PMID- 26372986 TI - Breastfeeding linked to quitting smoking. PMID- 26372985 TI - Feeding frenzy. PMID- 26372987 TI - Study finds no link between MMR and autism. PMID- 26372988 TI - Traumatic experiences linked to Type 1 diabetes. PMID- 26372989 TI - Screen time blamed for back pain in young people. PMID- 26372990 TI - Half of children bullied over looks. PMID- 26372991 TI - Children as young as ten using e-cigarettes. PMID- 26372992 TI - Eating disorders in Welsh teens at record high. PMID- 26372993 TI - Child transgender referrals quadruple. PMID- 26372994 TI - A day in the life of a breastfeeding lead health visitor. PMID- 26372996 TI - Achieving equitable workloads. PMID- 26372995 TI - Safeguarding school nurses. PMID- 26372997 TI - Lady in weighting. PMID- 26372998 TI - Member case study: case allocation tool. PMID- 26372999 TI - Member case study: profiling tool. PMID- 26373000 TI - Dietary allergies in breastfed babies. PMID- 26373001 TI - Lactation-related infections. PMID- 26373002 TI - Vitamin D deficiency: prevention and identification of risk. PMID- 26373003 TI - Overcoming breastfeeding challenges. PMID- 26373004 TI - Flying Start health visitors' views of implementing the Newborn Behavioural Observation: barriers and facilitating factors. AB - Investment in early intervention by health visitors to support positive parent infant relationships is a Welsh Government target. An initiative called 'Flying Start' (FS) employs health visitors to undertake intensive home visiting with families who have a new baby to promote positive family interactions. As part of this role FS health visitors utilise the Newborn Behavioural Observation (NBO) system to observe, assess, support and enhance relationships between parent(s) and child. A project was undertaken to evaluate implementation and make recommendations for future service improvement. This paper describes stage one of the project which set out to evaluate FS health visitors' views of NBO implementation by means of a questionnaire and identifies barriers and facilitating factors to its use. Stage 2 of the project was to identify how NBO use could be improved in health visiting practice, discussed in a further paper. Results revealed a majority of practitioners felt NBO implementation benefited parents and enhanced the parent-infant relationship. It was viewed as an important part of the FS health visitors' role. Barriers included lack of time coupled with chaotic home environments. Variations in practice were identified, contrary to local guidelines. Recommendations are made to enhance NBO implementation that include the development of an NBO champion to support practitioners and provide further training. PMID- 26373005 TI - To what extent do health visitors and school nurses have a voice in the policy process? AB - The purpose of the study was to explore the reciprocal impact of health policy on public health nursing and public health nursing on policy in England. The theoretical framework was critical social theory and the methodology was constructivist grounded theory (Charmaz, 2006). In the first phase of the research, initial scoping questionnaires and follow-up telephone interviews were conducted. Phase two consisted of detailed policy analyses and in phase three, extant documents were reviewed. The study identified potential barriers to public health nurses' full participation in the policy process and possible responses, including organizational changes in health care settings and curricula developments in the nursing education domain. The data collection for this study was carried out between 2008 and 2011. PMID- 26373006 TI - Exploring the impact of paternal imprisonment on infant mental health. AB - This paper draws from a study, which explored paternal absence through imprisonment and the impact of this on infant emotional wellbeing and mental health. Little evidence exists to demonstrate the impact of a father's imprisonment on infant involvement, attachment relationships and the consequences of such separation for both infant and father. A scoping study, synthesising literature gathered from a range of academic sources, allowed for exploration of key concepts and clarification of pertinent themes in this relatively under studied area. Findings suggest that maintaining father involvement while in prison is vital in promoting and maintaining positive infant mental health and that the health visitor is well placed to play a pivotal role in supporting the families of those within the criminal justice system. PMID- 26373007 TI - Last word with ... FIONA MCQUEEN. PMID- 26373008 TI - Hunt pledges 'national strategy' for child obesity. PMID- 26373010 TI - Quarter of UK children overweight. PMID- 26373009 TI - Online records may put children at risk. PMID- 26373011 TI - Mothers-to-be warned over paracetamol. PMID- 26373012 TI - UK ranked 26th for maternal wellbeing. PMID- 26373013 TI - Hidden peanut allergy in asthmatic children. PMID- 26373014 TI - Cannabis use before puberty could stunt growth in teens. PMID- 26373015 TI - A DAY IN THE LIFE OF A ... SCHOOL NURSE. PMID- 26373016 TI - The new government: what's in store? PMID- 26373017 TI - PART THREE: Caseloads special report. Community Practitioner discusses the burning issues for health visitors. PMID- 26373018 TI - Breastfeeding: myths and misconceptions. PMID- 26373019 TI - Sun exposure: know the risks. PMID- 26373020 TI - Salmonella in pets: the risk to children. PMID- 26373021 TI - Diabetes in children. PMID- 26373022 TI - Antenatal young parents: introducing a pathway to enhance health visiting practice. AB - Although their numbers have declined over the last 10 years, younger (teenage) parents are still one of the most disadvantaged client groups and have significantly poorer health outcomes for both themselves and their children.This article describes the author's creation of a Health Visiting practice pathway for this specific client group. The pathway was planned to promote a standardisation of service from all the health visiting teams across the Humber Foundation Trust area, aiming towards equity of service for all clients in this group. This is particularly important in a Trust which has a very diverse client population covering approximately 930 square miles. The article explores young parents' health issues and summarises why we should invest health visitor resources in this small but very specific client group. As a result of the project work, challenges and opportunities for health visiting practice were identified. Recommendations for both current and future practice are discussed. PMID- 26373023 TI - A community practitioner abroad: listening to women in Dailekh, Nepal. AB - Nepal is one of the poorest countries in the world, and has a strongly patriarchal culture. This study reports on methods used to explore women's opportunities in decision-making roles in Dailekh, Nepal. Action-based research was used to support women to identify barriers and to enable them to find solutions which could increase meaningful, practical and genuine representation. Participants were women in nominal positions of leadership in the community and subsequently also men in leadership roles. Focus groups and interviews enabled data to be collected and analysed using participatory and 'rich picture' tools. A five-stage framework approach was used to analyse data. A major theme of 'power' emerged comprised of supporting themes; 'place in society 'formal power,' informal power and 'voice'. These outcomes formed the basis for identifying viable action plans generated by the participants of both genders to promote meaningful involvement of women in community decision making. Women were clear that involving men and women in the actions was key to increasing success. PMID- 26373024 TI - Last word with ... WENDY NICHOLSON. PMID- 26373025 TI - We Must Not Waiver. PMID- 26373026 TI - The Teeth-Whitening Debacle. PMID- 26373027 TI - Making Lemonade is Your Best Bet. PMID- 26373028 TI - A Life of Service to Community and Profession. PMID- 26373029 TI - Preparing and Restoring Composite Resin Restorations. The Advantage of High Magnification Loupes or the Dental Surgical Operating Microscope. AB - Use of magnification, such as 6x to 8x binocular surgical loupes or the surgical operating microscope, combined with co-axial illumination, may facilitate the creation of stable composite resin restorations that are less likely to develop caries, cracks or margin stains over years of service. Microscopes facilitate observation of clinically relevant microscopic visual details, such as microscopic amounts of demineralization or caries at preparation margins; microscopic areas of soft, decayed tooth structure; microscopic amounts of moisture contamination of the preparation during bonding; or microscopic marginal gaps in the composite. Preventing microscope-level errors in composite fabrication can result in a composite restoration that, at initial placement, appears perfect when viewed under 6x to 8x magnification and which also is free of secondary caries, marginal staining or cracks at multi-year follow-up visits. PMID- 26373030 TI - Necrotizing Fasciltis Case Presentation and Literature Review. AB - Necrotizing fasciitis is a rare, rapidly progressing in- fection with significant morbidity and high mortality rates. Rarely does necrotizing fasciitis appear in the head and neck region; rather, it usually affects the limbs and abdomen of patients. This article presents our institution's experience with the disease and pro- vides a discussion of proposed treatment options. PMID- 26373032 TI - Inflammatory Myofibroblastic Tumor of the Oral Cavity. A Great Mimicker. AB - Inflammatory myofibroblastic tumor (IMT) is a seldom-described tumor of indefinite etiology and pathogenesis. It occurs primarily in the lungs, but has occurred in other extra-pulmonary sites. Histologically, these lesions appear as an inflammatory infiltrate within a variably myofibrotic background. Current evidence shows that inflammatory myofibroblastic tumors are neoplastic processes resulting from chromosomal translocations that frequently cause an overexpression of ALK kinase, often assessed using immunohistochemical studies. Currently, the biological behavior of oral IMT is still uncertain. This article illustrates the clinical, histological and operative features of a case of IMT of the oral cavity. PMID- 26373031 TI - Adhesive Approach Using Internal Coping for Vertical Root Fractured Teeth with Flared Root Canals. AB - Vertical root fractures are often observed in teeth with endodontic treatment and post space preparation. Frequently, because such teeth have flared root canals with thin dentin walls, conventional treatments are disadvantageous in terms of adhesiveness, sealability and risk of refracture. Here we devised an intentional replantation method that uses internal resin coping, with a reinforcing effect on thin root canal dentin. In two patients treated with this method, satisfactory conditions have been maintained. This report suggests that an intentional replantation method in which an internal resin coping is employed may be a useful therapy for fractured teeth with flared root canals. PMID- 26373033 TI - Segmental Dento-alveolar Intrusive Osteotomy in Posterior Maxilla with Lack of Inter-arch Distance for Prosthetic Rehabilitation. A Technique Combined with Sinus Floor Elevation. AB - The aim of this paper is to present a technique for segmental dento-alveolar intrusive osteotomy in a posterior maxilla with lack of inter-arch distance for prosthetic rehabilitation combined with sinus floor elevation. METHODS: A full thickness flap is elevated exposing the lateral wall of the maxillary sinus. A lateral window is opened and the Schneiderian membrane elevated. Segmental dento alveolar osteotomy is performed. After complete detachment of the segment, it is adapted and fixed to the new position using the pre-prepared guide, making sure not to damage or perforate the Schneiderian membrane. RESULTS: Four cases of segmental dento-alveolar intrusive osteotomy in a posterior maxilla combined with sinus floor elevation were performed utilizing the above-mentioned technique. All surgeries went according to plan, and healing was uneventful except for swelling and pain that lasted for 10-14 days post- operatively. The opposing dentition was later treated by implant placement. The average follow-up time for those cases was 5.4 months. Vitality test four months after surgery was positive. CONCLUSION: The presented technique for segmental dento-alveolar intrusive osteotomy combined with sinus floor elevation can serve as a viable treatment option in the posterior maxilla with lack of inter-arch distance due to severe overeruption. PMID- 26373034 TI - Comparison of Cone-beam Computed Tomography and Multi-slice Spiral Computed Tomography Bone Density Measurements in the Maxilla and Mandible. AB - The purpose of this study was to compare cone-beam computer tomography (CBCT) and multi-slice spiral computed tomography (MSCT) bone density measurements in the maxilla and mandible to determine whether any discrepancies between imaging modalities exist. MATERIAL & METHODS: 33 sets of CBCT and MSCT scans were evaluated using Simplant software. Density measurements were made in eight regions of interest on each scan and were compared and analyzed. RESULTS: Correlation of density measurements at specific regions of interest between CBCT and MSCT was only fair and ranged from 0.61-0.86. High-density areas, such as the anterior mandible, showed a higher correlation between imaging modalities than low-density regions, such as the posterior maxilla. CONCLUSION: Care should be taken when relying upon CBCT to determine bone density, especially in low-density regions such as the posterior maxilla. PMID- 26373035 TI - Standards, Regulation and Registration of Dental Laboratories. An Industry Update. AB - State dental associations are showing increased interest in maintaining current standards and regulations affecting the dental laboratory industry as mandated by the Food and Drug Administration. The domestic dental laboratory industry is being significantly stressed by foreign competition, rapid technology development and unprecedented consolidation, which are changing the way that prosthetic devices and restorations are manufactured and delivered to dentists. Of paramount importance to the prescribing dentist is the accurate documentation of the source and materials being used in prostheses being delivered to patients. PMID- 26373036 TI - Applications of Nanoparticles for Anticancer Drug Delivery: A Review. AB - Biodegradable nanometer-sized particles have novel structural and physical properties that are attracting great interests from pharmaceuticals for the targeted delivery of anticancer drugs and imaging contrast agents. These smart nanoparticles are designed to ferry chemotherapeutic agents or therapeutic genes into malignant cells while sparing healthy cells. In this review, we describe currently clinically used chemotherapeutics in nanoparticle formulation and discuss the current status of nanoparticles developed as targeting delivery systems for anticancer drugs, with emphasis on formulations of micelles, liposome, polymeric nanoparticles, gold nanoparticle dendrimers, and bionanocapsules. PMID- 26373037 TI - Preparation and Characterization of Folate Targeting Magnetic Nanomedicine Loaded with Gambogenic Acid. AB - To engineer multifunctional nanomedicines for simultaneous imaging and therapy of cancer cells, we have prepared Gambogenic acid (GNA) loaded folic acid (FA) armed MNPs (FA-GNA-MNPs) to target the folate receptor (FR) positive cancer cells. The FA-GNA-MNPs have been prepared by a facile method, which have been further characterized by SEM, TEM, IR and UV-vis spectra. And the cytotoxicity of FA-GNA MNPs to HeLa and A549 cells was assessed using the MTT assay. The FA-GNA-MNPs (with loading efficiency of 4.35%) showed sustained liberation of GNA molecules (with 73.46% release in 96 h). The mean particle diameter (MD) of FA-GNA-MNPs and the polydispersity index (PDI) are 254.3 nm and 0.139, respectively. The cytotoxicity of free GNA and FA-GNA-MNPs toward HeLa cells showed that FA-GNA MNPs was more cytotoxic than GNA. Based on these findings, it suggests that FA GNA-MNPs would be as a novel multifunctional nanomedicine/theranostic for concurrent targeting, imaging and therapy of the FR-positive cancer cells. PMID- 26373038 TI - Diamine Functionalized Cubic Mesoporous Silica for Ibuprofen Controlled Delivery. AB - A diamine functionalized cubic mesostructured KIT-6 (N-KIT-6) has been prepared by post-synthetic method using calcined mesoporous KIT-6 with a diamine source, i.e., N-'[3-(tri methoxysilyl)- propyl]'ethylenediamine. The KIT-6 mesoporous silica used for N-KIT-6 was synthesized under weak acidic hydrothermal method using bitemplates, viz., Pluronic P123 and 1-butanol. The synthesized mesoporous materials, KIT-6 and N-KIT-6, have been characterized by the relevant instrumental techniques such as SAXS, N2 sorption isotherm, FT-IR, SEM, TEM and TGA to prove the standard mesoporous materials with the identification of diamine groups. The characterized mesoporous materials, KIT-6 and N-KIT-6, have been extensively used in the potential application of controlled drug delivery, where ibuprofen (IBU) employed as a model drug. The rate of IBU adsorption and release was monitored by UV vis-spectrometer. On the basis of the experimental results of controlled drug delivery system, the results of IBU adsorption and releasing rate in N-KIT-6 are higher than those of KIT-6 because of the higher hydrophobic nature as well as rich basic sites on the surface of inner pore wall silica. PMID- 26373039 TI - Lipid-Polymer Nanoparticles for Folate-Receptor Targeting Delivery of Doxorubicin. AB - A biocompatible PLGA-lipid hybrid nanoparticles (NPs) was developed for targeted delivery of anticancer drugs with doxorubicin (DOX). The hydrodynamic diameter and zeta potential of DOX-loaded PLGA-lipid NPs (DNPs) were affected by the mass ratio of Lipid/PLGA or DSPE-PEG-COOH/Lecithin. At the 1:20 drug/polymer mass ratio, the mean hydrodynamic diameter of DNPs was the lowest (99.2 1.83 nm) and the NPs presented the encapsulation efficiency of DOX with 42.69 1.30%. Due to the folate-receptor mediated endocytosis, the PLGA-lipid NPs with folic acid (FA) targeting ligand showed significant higher uptake by folate-receptor-positive MCF 7 cells as compared to PLGA-lipid NPs without folate. Confocal microscopic observation and flow cytometry analysis also supported the enhanced cellular uptake of the FA-targeted NPs. The results indicated that the FA-targeted DNPs exhibited higher cytotoxicity in MCF-7 cells compared with non-targeted NPs. The lipid-polymer nanoparticles provide a solution of biocompatible nanocarrier for cancer targeting therapy. PMID- 26373040 TI - pH Responsive Release of Doxorubicin to the Cancer Cells by Functionalized Multi Walled Carbon Nanotubes. AB - The main aim of the current study is to formulate the Doxorubicin loaded functionalized carbon nanotubes to deliver the drug only to the cancer cells by using pH difference. Multi walled Carbon Nanotubes (MWNTs) have been identified as an efficient drug carrier through pi-pi linkage, because this covalent bond is sensitive to tumor microenvironments. This bond is acid cleavable, thereby providing a strong pH-responsive drug release, which may facilitate effective release near the acidic tumor microenvironment and thus reduces its overall systemic toxicity. Doxorubicin was released at low pH and taken up by tumor cells via adenosine triphosphate (ATP)-dependent endocytosis. By varying the Concentration of MWNTs with the Doxorubicin, it forms a conjugate. It is due to supra molecular interactions between the drug and MWNTs, so it shows high loading, prolonged release and improved cytotoxicity against cancer cells. This study shows the phenomenal pH responsive drug release to the cancerous microenvironment and prolonged release. This study suggests that MWNTs have a great potential as a drug carrier; the efficient formulation strategy requires further study. PMID- 26373041 TI - Microencapsulated Multicellular Tumor Spheroids as a Tool to Test Novel Anticancer Nanosized Drug Delivery Systems In Vitro. AB - In the study, MCF-7 human breast adenocarcinoma cells were used to study cytotoxicity of novel anticancer nanosized formulations, such as docetaxel-loaded nanoemulsion and liposomal formulation of a lipophilic methotrexate (MTX) prodrug. In vitro study of cytotoxicity was carried out in 2 models, namely using 3D in vitro model based on multicellular tumor spheroids (MTS) and 2D monolayer culture. MTS were generated by tumor cell cultivation within alginate oligochitosan microcapsules. In the case of the monolayer culture, cell viability was found to be 25, 18 and 12% for the samples containing nanoemulsion at concentrations 20, 300 and 1000 nM of docetaxel, respectively, after 48 hs incubation. For MTS these values were higher, namely 33, 23 and 18%, respectively. Cytotoxicity of liposomal MTX prodrug-based formulation with final concentration of 1, 2, 10, 50, 100 and 1000 nM in both models was also studied. MTX liposomal formulation demonstrated lower cytotoxicity on MTS compared to intact MTX. Moreover, MTS were also more resistant to both liposomal formulation and intact MTX than the monolayer culture. Thus, at 1000 nM MTX in the liposomal form, cell viability in MTS was 1.4-fold higher than that in the monolayer culture. MTS could be proposed as a promising tool to test novel anticancer nanosized formulations in vitro. PMID- 26373042 TI - Polymorphisms in NEIL-2, APE-1, CYP2E1 and MDM2 Genes are Independent Predictors of Gastric Cancer Risk in a Northern Jiangsu Population (China). AB - China is one of the countries with the highest incidence of gastric cancer, and accounts for over 40% of all new gastric cancer cases in the world. Genetic factors as well as environmental factors play a role in development of gastric cancer. To investigate the independent roles of single nucleotide polymorphisms (SNPs) in base excision repair (BER) genes (APE1 and NEIL2), carcinogen metabolism gene (CYP2E1) and tumor suppressor pathway gene (MDM2) for gastric cancer susceptibility in a Chinese population, we conducted a hospital based case control study to evaluate the potential association between these polymorphisms and susceptibility to gastric cancer in a Northern Jiangsu population. We also associated the NEIL-2 mRNA expression with the studied NEIL2 SNP genotypes to assess whether the genotypes have influence on the NEIL2 mRNA (hence protein) expression. Five SNPs, APE 1 (rs2275008), NEIL 2 (rs804270), MDM2 (rs2279744), and CYP 2E1 (rs2480256 and rs2031920), were genotyped by TaqMan assays in 105 gastric cancer cases and 118 controls. Genotype frequency distribution showed that the APE 1 SNP (rs2275008), NEIL 2 SNP (rs804270), MDM2 SNP (rs2279744), and CYP 2E1 SNP (rs2031920) had more mutant alleles in gastric cancer cases than controls (76.19, 68.57, 54.29, and 43.81%, respectively), while CYP 2E1 SNP (rs2480256) had large percentage of both alleles (43.81%). Risk analysis revealed that there was increased risk for gastric cancer in subjects with mutant alleles in APE 1 (rs2275008: OR 5.49, 95% CI = 2.6-5.7, p <.0001), NEIL 2 (rs804270: OR 2.3, 95% CI = 1.22-4.3, p=0.01), MDM2 (rs2279744: OR 14.65, 95% CI = 5.63-8.15, p < .0001), and CYP 2E1 (rs2031920: OR 8.385, 95% CI = 3.2-5.3, p < .0001) SNPs. Moreover, the NEIL2 mRNA expression analysis showed that there was significant differential expression of NEIL2 mRNA among the randomly tested NEIL2 genotypes (p = 0.005), with low expression seen in variant genotypes than in other genotypes. In conclusion, variant alleles in the NEIL2 (rs804270), APE1 (rs2275008), CYP2E1 (rs2031920) and MDM2 (rs2279744) SNPs may independently influence susceptibility to gastric cancer in a Northern Jiangsu Chinese population. The genotypes may also independently influence their respective gene mRNA expression, as seen in our study, where there was differential expression of the NEIL2 mRNA among the genotypes, with low NEIL2 mRNA expression seen in the variant genotype. PMID- 26373043 TI - Synthesis of Au Nanostars and Their Application as Surface Enhanced Raman Scattering-Activity Tags Inside Living Cells. AB - This work presents the synthesis and characterization of Au nanostars (AuNSs) and demonstrates their application as surface enhanced Raman scattering (SERS) activity tags for cellular imaging and sensing. Nile blue A (NBA) and bovine serum albumin (BSA) were used as Raman reporter molecules and capping materials, respectively. The SERS-activity tags were tested on human lung adenocarcinoma cell (A549) and alveolar type II cell (AT II) and found to present a low level of cytotoxicity and high chemical stability. These SERS-activity tags not only can be applied in multiplexed cellular imaging, including dark field imaging, transmission electron microscopy (TEM) and SERS imaging, but also can be used for cellular sensing. The SERS spectra clearly identified cellular important components such as proteins, nucleic acids, lipids, and carbohydrates. This study also shows that endocytosis is the main channel of tags internalized in cells. The AuNSs exhibiting strong surface enhanced Raman effects are utilized in the design of an efficient, stable SERS-activity tag for intracellular applications. PMID- 26373044 TI - Polymeric Nanoparticles of Enoxaparin as a Delivery System: In Vivo Evaluation in Normal Rats and in a Venous Thrombosis Rat Model. AB - Enoxaparin is an anticoagulant widely used in the treatment and prophylaxis of deep vein thrombosis (DVT). The subcutaneous route of administration, sometimes in repeated doses during 24 hours, represents a limitation to its use. Thus, the development of a product that can be administered either subcutaneously, in a smaller number of applications becomes a major challenge, with interesting clinical applications. The use of a system for sustained release of drugs can help to meet that goal, by protecting and enabling a gradual released of the agent. This study consisted of the evaluation of in vivo anticoagulant and antithrombotic activity of biodegradable nanoparticles of poly (epsilon caprolactone) (PCL) with enoxaparin after subcutaneous injection. The nanoparticles were prepared by the method of double emulsion (w/o/w) and solvent evaporation. Subcutaneous enoxaparin encapsulated in PCL nanoparticles (1000 IU/kg) showed a sustained release in vivo for up to 12 hours (Cmax 0.62 IU/mL) a significantly longer period (P < 0.01) when compared to free enoxaparin (1000 IU/Kg) that disappeared after 9 hours (Cmax 1.50 IU/mL), however with lower anti Xa activity. The antithrombotic action of enoxaparin-nanoparticles was tested in a DVT model by stasis in rats. There were virtually no formation of venous thrombosis in any of the rats that received enoxaparin encapsulated in nanoparticles (0.03 mg), with a significant difference when compared to groups that received saline (17.2 mg, P < 0.001) and free enoxaparin (2.87 mg, P = 0.001). In summary, enoxaparin-encapsulated in polymeric nanoparticles showed a sustained release for a greater period than that of enoxaparin, and with excellent antithrombotic action. These results corroborate the promising use of pharmacological nanoparticles in clinical practice. PMID- 26373045 TI - Bone Marrow Stem Cells Response to Collagen/Single-Wall Carbon Nanotubes-COOHs Nanocomposite Films with Transforming Growth Factor Beta 1. AB - Single-wall carbon nanotubes (SWNTs) have attractive biochemical properties such as strong cell adhesion and protein absorption, which are very useful for a cell cultivation scaffold. In this study, collagen/SWNT-COOHs nanocomposite films composed of regenerated fish collagen and SWNT-COOHs (0, 0.5, 1.0 and 2.0 weight percent) were prepared by mixing solubilized pepsin-soluble collagen with solutions of SWNT-COOHs. Morphological observation by SEM indicated the homogenous dispersion of SWNT-COOHs in the collagen matrix. The application of FTIR confirmed that the process we applied to prepare the composites did not destroy the native structures of collagen and composites were crosslinked by D ribose. The biocompatibility was evaluated in vitro using SD rat bone marrow stem cells (BMSCs). Compared with films without transforming growth factor beta 1 (TGF beta1), films with TGF-beta1 had superior performance on promotion of cell growth. Compared with pure collagen film with TGF-beta1, SWNT-containing films might promote cellular functions by adsorbing more growth factors. In conclusion, the study suggested that the collagen/SWNT-COOHs nanocomposite films with TGF beta1 were expected to be useful scaffolds in cartilage tissue engineering. PMID- 26373046 TI - The Effect of Novel Mercapto Silane Systems on Resin Bond Strength to Dental Noble Metal Alloys. AB - Self-assembled monolayers of thiols (RSH), which are key elements in nanoscience and nanotechnology, have been used to link a range of materials to planar gold surfaces or gold nanoparticles. In this study, the adhesive performance of mercapto silane systems to dental noble metal alloys was evaluated in vitro and compared with that of commercial dental primers. Dental gold-palladium-platinum (Au-Pd-Pt), gold-palladium-silver (Au-Pd-Ag), and palladium-silver (Pd-Ag) alloys were used as the bonding substrates after air-abrasion (sandblasting). One of the following primers was applied to each alloy: (1) no primer treatment (control), (2) three commer- cial primers: V-Primer, Metal Primer II, and M.L. Primer, and (3) two experimental silane primer systems: 2-step application with 3 mercaptopropyltrimethoxysilane (SPS) (1.0 wt%) and then 3 methacryloxypropyltrimethoxysilane (MPS) (1.0 wt%), and a silane blend consisting of SPS and MPS (both 1.0 wt%). Composite resin cylinders with a diameter of 2.38 mm were bonded to the surfaces and irradiated for 40 sec using a curing light. After storage in water at 37 degrees C for 24 h, all the bonded specimens were thermocycled 5000 times before the shear bond strength test. Regardless of the alloy type, the mercapto silane systems (both the 2-step and blend systems) consistently showed superior bonding performance than the commercial primers. Contact angle analysis of the primed surfaces indicated that higher resin bond strengths were produced on more hydrophilic alloy surfaces. These novel mercapto silane systems are a promising alternative for improving resin bonding to dental noble metal alloys. PMID- 26373047 TI - Cerium Oxide Nanoparticles Decorated Graphene Nanosheets for Selective Detection of Dopamine. AB - The fabrication of a novel amperometric biosensor based on selective determination of dopamine (DA) using nafion coated cerium oxide nanoparticles (NPs) decorated graphene nanosheets (CeO2-HEG-nafion) as a transducer candidate is reported. Graphene was synthesized by hydrogen exfoliation technique. Decoration of CeO2NPs over graphene nanosheets was done by chemical reduction method. The electrochemical impedance spectroscopy (EIS) study shows the enhanced electron transfer kinetics of the composite compared to HEG modified and bare glassy carbon electrode (GCE). The response of the composite towards dopamine displays a lower oxidation potential of 0.23 V and a high oxidation current. The sensor exhibits linearity from 10 uM to 780 uM with a detection limit of 1 uM. In the presence of nafion, it shows excellent selectivity for coexisting interference species like Ascorbic acid (AA) and Uric acid (UA). The excellent performance of the biosensor can be attributed to large active surface area, enhanced electron transfer kinetics and high catalytic activity of the composite. PMID- 26373048 TI - Interface Adsorption Taking the Most Advantageous Conformation for Electron Transfer Between Graphene and Cytochrome c. AB - Most designed functions in biomedical nanotechnology are directly influenced by interactions of biological molecules with nano surfaces. Here, we explored and detected the most favorable adsorption conformation of cytochrome c on graphene by measuring the adsorption energy, the number of contact atoms, and the minimal distance between protein and surface. From the root mean square deviation of the protein backbone, the radius of gyration, and the proportion of secondary structure, it is revealed that cytochrome c does not deform significantly and the secondary structures are preserved to a large extent. The residues, Lys, Phe and Thr contribute significantly to the adsorption of cytochrome c to graphene. The long hydrophobic and flexible alkyl tail of Lys, the pi-pi stacking interaction between Phe and graphene, and the presence of abundant Thr constitute the driving force for the stable adsorption of cytochrome c on graphene. Cytochrome c is adsorbed to graphene with the group heme lying almost perpendicular to the graphene, and the distance between Fe atom and the graphene is 10.15 A, which is shorter than that between electron donor and receptor in many other biosystems. All the results suggest that the most favorable adsorption takes the most advantageous conformation for electron transfer, which promotes significantly the electron transfer between graphene and cytochrome c. The findings might provide new and important information for designs of biomedical devices or products with graphene-based nanomaterials. PMID- 26373049 TI - Characterization and Enhanced Visible-Light Photocatalytic Properties of {001} Facets-Exposed TiO2-Reduced Graphene Oxide Nanocomposites. AB - The efficient visible-light active nanocomposites of {001} facets-exposed TiO2 reduced graphene oxide (RGO) were fabricated by a simple one-step solvothermal approach for application in photocatalytic degradation. The morphology, structure and optical properties of the nanocomposites were well characterized by X-ray diffraction, transmission electron microscopy, Raman spectroscopy, X-ray photoelectron spectroscopy and UV-vis diffuse reflectance spectroscopy. The results indicated that the TiO2 nanoflakes with exposed {001} facets were well dispersed and contact closely with the surface of graphene sheets via the formation of Ti-O-C bonds. The percentage of the {001} facets which have higher chemistry activity in anatase TiO2 was about 71.3%. The incorporation of RGO with TiO2 increased the light absorption in the whole visible region and displayed a red-shift absorption edge, accelerated the separation of photogenerated electron hole pairs, furthermore, effectively enhanced the photocatalytic activity of TiO2 under the visible light. The efficiency of the system was significantly influenced by the content of RGO. The optimum content of RGO was 5 wt% for the maximum photocatalytic efficiency. PMID- 26373050 TI - Optimizing Performance Parameters of Chemically-Derived Graphene/p-Si Heterojunction Solar Cell. AB - Chemically-derived graphene have been synthesized by modified Hummers method and reduced using sodium borohydride. To explore the potential for photovoltaic applications, graphene/p-silicon (Si) heterojunction devices were fabricated using a simple and cost effective technique called spin coating. The SEM analysis shows the formation of graphene oxide (GO) flakes which become smooth after reduction. The absence of oxygen containing functional groups, as observed in FT IR spectra, reveals the reduction of GO, i.e., reduced graphene oxide (rGO). It was further confirmed by Raman analysis, which shows slight reduction in G-band intensity with respect to D-band. Hall effect measurement confirmed n-type nature of rGO. Therefore, an effort has been made to simu- late rGO/p-Si heterojunction device by using the one-dimensional solar cell capacitance software, considering the experimentally derived parameters. The detail analysis of the effects of Si thickness, graphene thickness and temperature on the performance of the device has been presented. PMID- 26373052 TI - High Performance Photocatalytic Degradation by Graphene/Titanium Nanotubes Under Near Visible Light with Low Energy Irradiation. AB - In this study, a novel titanium dioxide nanotubes and graphene (GR-TNT) nano composite was synthesized through a hydrothermal method. The introduction of GR was aimed to reduce the rapid electron-hole recombination of TiO2 thus improving their phtotcatalytic behavior in real application. The catalysts were characterized by using FT-IR, UV-Vis, XRD, TEM. The degradation results showed that the combined GR and TNT composite could obviously increase the photocatalysis efficiency for Reactive Black 5. The RBk5 removal can reach up to 90% under the near visible light irradiation for 3 h with the irradiation intensity less than 1.0 mW cm(-2) and the 10% GR-TNT dosage of 0.1 g L(-1) at original pH (about 5.8). Further experiments were done to probe the mechanism of the photocatalytic reaction catalyzed by GR-TNT composite. EDTA and t-BuOH, which were used as holes and radical scavengers, was used to determine the active oxidative species in the system and the results suggested a holes-driven oxidation mechanism. This study provides a new prospect of using. PMID- 26373051 TI - Chemical Vapor Deposition of Phosphorous- and Boron-Doped Graphene Using Phenyl Containing Molecules. AB - Simultaneous chemical vapor deposition (CVD) of graphene and "in-situ" phosphorous or boron doping of graphene was accomplished using Triphenylphosphine (TPP) and 4-Methoxyphenylboronic acid (4-MPBA). The TPP and 4-MPBA molecules were sublimated and supplied along with CH4 molecules during graphene growth at atmospheric pressure. The grown graphene samples were characterized using Raman spectroscopy. Phosphorous and boron presence in phosphorous and boron doped graphene was confirmed with Auger electron spectroscopy. The possibility of obtaining phosphorous and boron doped graphene using solid-source molecule precursors via CVD can lead to an easy and rapid production of modified large area graphene. PMID- 26373053 TI - Data Archive Based on Graphene Nanoflake Shuttle Encapsulated in Bi-Layered Graphene Nanoribbon. AB - We present advanced schematics of graphene-nanoflake (GNF) shuttle-memory using the GNF encapsulated within bi-layered graphene nanoribon (GNR) like a sandwich and investigate its energetic and dynamic properties via classical molecular dynamics simulations. This work explicitly demonstrates that GNF shuttle encapsulated in bi-layered GNR is applicable to nonvolatile memory. Its energetics and the dynamic properties obtained from atomic-scale calculations clearly showed that this GNF shuttle encapsulated in bi-layered GNR had bi-stable minima energy position in the vdW potential energy plot. Such a shuttle-memory can facilitate the development of switches, sensors, and quantum computing as well as data archives. PMID- 26373054 TI - Nitrogen-Doped Three Dimensional Graphene for Electrochemical Sensing. AB - The rational assembly and doping of graphene play an crucial role in the improvement of electrochemical performance for analytical applications. Covalent assembly of graphene into ordered hierarchical structure provides an interconnected three dimensional conductive network and large specific area beneficial to electrolyte transfer on the electrode surface. Chemical doping with heteroatom is a powerful tool to intrinsically modify the electronic properties of graphene due to the increased free charge-carrier densities. By incorporating covalent assembly and nitrogen doping strategy, a novel nitrogen doped three dimensional reduced graphene oxide nanostructure (3D-N-RGO) was developed with synergetic enhancement in electrochemical behaviors. The as prepared 3D-N-RGO was further applied for catechol detection by differential pulse voltammetry. It exhibits much higher electrocatalytic activity towards catechol with increased peak current and decreased potential difference between the oxidation and reduction peaks. Owing to the improved electro-chemical properties, the response of the electrochemical sensor varies linearly with the catechol concentrations ranging from 5 uM to 100 uM with a detection limit of 2 uM (S/N = 3). This work is promising to open new possibilities in the study of novel graphene nanostructure and promote its potential electrochemical applications. PMID- 26373055 TI - Molecular Dynamics Simulations of a C60 Molecule Adsorbed on Sinusoidal Graphene Nanoflake. AB - We have investigated the motion of a C60 molecule absorbed on sinusoidal graphene nanoflake (GNF) via molecular dynamics simulations. Since C60 deposited on sinusoidal GNF is favorable on energetic grounds, the C60 molecule moved toward one of the valleys of sinusoidal GNF without energy barrier. So no sooner the C60 molecule was deposited on the sinusoidal GNF, then the C60 molecule immediately began to move toward the valley of the sinusoidal GNF Since the position of the C60 molecule can be changed by externally applied force fields and has a binding energy of 0.754 eV in the valley of sinusoidal GNF, the sinusoidal C60/GNF can be applied to a switchable nonvolatile memory device. This work provides the probability of alternative 'bucky shuttle' memory based on the sinusoidal C60/GNF hybrid nanostructure. PMID- 26373056 TI - Band Gap Tuning of h-MoO3 Nanocrystals for Efficient Visible Light Photocatalytic Activity Against Methylene Blue Dye. AB - The photocatalytic degradation of methylene blue (MB) dye in aqueous solution was investigated using hexagonal molybdenum oxide (h-MoO3) nanocrystals under visible light irradiation. Chemical precipitation method was utilized to synthesize h MoO3 and control over the crystal size, shape and distribution were characterized by using HNO3 and HCl as precipitating reagents. The photocatalysts were examined through X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM) and energy dispersive X-ray spectrum (EDX) for structural, functional, surface morphology and elemental analysis, respectively. The XRD results revealed that the samples were in single phase hexagonal crystal structure. XRD peak broadening analysis was used for crystallite size and strain estimation. The particles were anisotropic in nature and showed one dimensional (1-D) rod structure with hexagonal cross section. Further, the crystal phase stability, optical absorption and emission properties were studied by thermo gravimetric analysis (TGA), diffuse reflectance spectroscopy (DRS) and photoluminescence (PL) measurements, respectively. The photocatalytic results demonstrated that the photocatalytic activity of h-MoO3 synthesized using HCl was improved, in comparison to that of HNO3 utilized h-MoO3 sample. PMID- 26373057 TI - Preparation for CeO2/Nanographite Composite Materials and Electrochemical Degradation of Phenol by CeO2/Nanographite Cathodes. AB - CeO2/nanographite (CeO2/nano-G) composite materials were got by chemical precipitation method with nanographite (nano-G) and cerous nitrate hexahydrate as raw materials. The microstructures of CeO2/nano-G composite materials were characterized by means of SEM, XRD, XPS and Raman. The cathodes were made by nano G and CeO2/nano-G composite materials, respectively. The electrolysis phenol was conducted by the diaphragm cell prepared cathode and the Ti/RuO2 anode. The results indicated that the Cerium oxide is mainly in nanoscale spherical state, uniformly dispersed in the nanographite sheet surface, and there are two different oxidation states for elemental Ce, namely, Ce(III) and Ce(IV). In the diaphragm electrolysis system with the aeration conditions, the degradation rate of phenol reached 93.9% under 120 min's electrolysis. Ceria in the cathode materials might lead to an increase in the local oxygen concentration, which accelerated the two-electron reduction of O2 to hydrogen peroxide (H2O2). The removal efficiency of phenol by using the CeO2/nano-G composite cathode was better than that of the nano-G cathode. PMID- 26373058 TI - Nanostructured Thin Film Silicon Anodes for Li-Ion Microbatteries. AB - Thin film microbatteries require electrode materials with high areal specific capacities and good cyclability. Use of vapor-deposited silicon thin films as anodes in Li-ion microbatteries offers the advantage of high capacity as well as compatibility with other processes used for microsystem fabrication. Unfortunately, monolithic silicon films greater than 200 nm in thickness pulverize during lithiation and delithiation. We have used metal-assisted chemical-etching of sputter-deposited amorphous silicon films to make nanoporous silicon layers and arrays of silicon nanopillars as a means of achieving anodes with high areal capacity and good cyclability. We have compared the performance of these nanostructured layers with the performance of monolithic silicon films in Li half-cells. A reduced first cycle coulombic efficiency was observed in all cases and was attributed to the irreversible formation of Li2O due to the presence of oxygen in the sputter-deposited silicon films. This was controlled through modifications of the sputtering conditions. As expected, monolithic films thicker than 200 nm showed poor cycling performance due to pulverization of the film. Nanoporous silicon showed good initial cycling performance but the performance degraded due to porosity collapse and delamination. Arrays of silicon nanopillars made from 750 nm silicon films exhibited good cycling, rate performance and an areal capacity (0.20 mA h cm(-2)) 1.6 times higher than what could be obtained with monolithic Si films with similar cyclability. PMID- 26373059 TI - Solvothermal Synthesis and Formation Mechanism of Potassium Sodium Niobate Mesocrystals Under Low Alkaline Conditions. AB - Pure-phase (K, Na)NbO3 (KNN) powders with orthorhombic symmetry were successfully synthesized by solvothermal method using isopropanol as solvent, without the addition of water. The as-prepared powders were characterized by X-ray diffraction, scanning electron microscopy and energy dispersive spectrometry to show the variation of phase, morphology, size distribution and chemical composition under different synthetic conditions, such as fill factors (FF) of the solvothermal system and alkalinity of the starting solution. Compared with the traditional hydrothermal method and the so-called solvothermal method (water aided in fact), small grains with well crystallinity were obtained using 100% isopropanol as reaction medium. The results indicate that both fill factor and alkalinity have significant effects on the phase structure and size distribution of the as-obtained KNN powders. Pure orthorhombic perovskite-structured KNN powders with a grain size of 100 nm were synthesized at the following condition: reaction time, 16 h; reaction temperature, 240 degrees C; fill factor, 70%; and alkalinity, 1 M. Small grains (~100 nm) tend to form mesocrystals (~10 um) with tetrakaidecahedron structures, and the possible formation mechanism was proposed. The solvothermal method without the addition of water is a promising alternative to synthesize pure and refined powders under mild reaction conditions. PMID- 26373060 TI - Enhanced Photovoltaic Performance in Polypyrrole Nanoparticles Counter Electrode Due to Incorporation of Multi-Walled Carbon Nanotubes. AB - In this present work, Multi-walled carbon nanotubes (MWNTs) with different content by weight (10%, 20%, 30%, 50% and 70%) are introduced into Polypyrrole nanoparticles (PPy NP) matrix and fabricated as Pt free counter electrodes (CEs) for dye-sensitized solar cell (DSSC). For comparison DSSCs using pristine PPy NP, MWNTs and Platinum (Pt) were also fabricated. The incorporation of MWNTs acts as conductive channel and co-catalyst to the PPy NP CEs in the reduction of li to I . The electrochemical catalytic activities of different CEs were analysed by Cyclic Voltammetry (CV) and Electrochemical Impedance Spectroscopy (EIS) and photovoltaic performance was studied under standard AM 1.5 sunlight illumination. It was observed that incorporation of MWNTs in the PPy NP CE greatly enhanced the catalytic activity for I3 reduction and significantly reduced the charge transfer resistance in the PPy NP/MWNTs composite CE finally improving short-circuit photocurrent density, fill factor, open circuit voltage and power conversion efficiency of DSSC. DSSC fabricated from PPy NP/MWNTs composite CE with 50% MWNTs content reached the highest photoconversion efficiency of 5.80% which is 91% that of Pt CE based DSSC (6.37%). PMID- 26373061 TI - A Simple Combustion Synthesis and Optical Studies of Magnetic Zn1-xNi(x)Fe2O4 Nanostructures for Photoelectrochemical Applications. AB - Ni-doped ZnFe2O4 (Ni(X)Zn1-x,Fe2O4; x = 0.0 to 0.5) nanoparticles were synthesized by simple microwave combustion method. The X-ray diffraction (XRD) confirms that all compositions crystallize with cubic spinel ZnFe2O4. The lattice parameter decreases with increase in Ni content resulting in the reduction of lattice strain. High resolution scanning electron microscope (HR-SEM) and transmission electron microscope (HR-TEM) images revealed that the as-prepared samples are crystalline with particle size distribution in 42-50 nm range. Optical properties were determined by UV-Visible diffuse reflectance (DRS) and photoluminescence (PL) spectroscopy respectively. The saturation magnetization (Ms) shows the superparamagnetic nature of the sample for x = 0.0-0.2, whereas for x = 0.3-0.5, it shows ferromagnetic nature. The Ms value is 1.638 emu/g for pure ZnFe2O4 sample and it increases with increase in Ni content. Photoelectrochemical (PEC) measurements showed a significant increase of photocurrent density with increase in the Ni-dopant, and 0.5% Ni-doped ZnFe2O4 sample was found to show the better photoresponse than the other doping concentrations. PMID- 26373062 TI - Synthesis of Polyaniline-Coated Ordered Mesoporous Carbon Composite Electrode Material for Supercapacitor and Its Enhanced Electrochemical Performance. AB - The polyaniline-coated ordered mesoporous carbon (PCOMC) material was prepared by chemical polymerization of aniline monomers on the ordered mesoporous carbon (OMC). The synthesized PCOMC materials were characterized by scanning electron microscopy, transmission electron microscopy, nitrogen adsorption-desorption isotherms and Fourier infrared spectroscopy. It was demonstrated that the polyaniline was successfully incorporated and well deposited on the external surface and inner pores of the OMC material. Furthermore, the electrochemical performance of the original OMC and PCOMC materials are compared by using cyclic voltammetry, electrochemical impedance spectroscopy, and galvanostatic charge discharge tests. The results showed that the electrochemical performance of the OMC material was enhanced after the incorporation of polyaniline. The specific capacitance of PCOMC electrode (813.4 F/g) measured by cyclic voltammetry at the scan rate of 2 mV/s was much higher than that of the OMC electrode (200.9 F/g). The discharge specific capacitance of the PCOMC supercapacitor could be kept at 119.4 F/g when the current density was 5 A/g, indicating its good rate performance even at high charge/discharge current density. Moreover, the PCOMC supercapacitor exhibited long cycling stability with the capacitance retention remained 77% after 3500 cycles. PMID- 26373063 TI - Fabrication and Characterization of n-ZnO Hexagonal Nanorods/p-Si Heterojunction Diodes: Temperature-Dependant Electrical Characteristics. AB - This paper reports the temperature-dependant electrical characteristics of n-ZnO hexagonal nanorods/p-Si heterojunction diodes. The n-ZnO hexagonal nanorods were grown on p-Si substrate by a simple thermal evaporation process using metallic zinc powder in the presence of oxygen. The spectroscopic characterization revealed well-crystalline nanorods, quasi-aligned to the substrate and possessing hexagonal shape. The as-grown nanorods exhibited a strong near-band-edge emis- sion with very weak deep-level emission in the room-temperature photoluminescence spectrum, confirming good optical properties. Furthermore, the electrical properties of as-grown ZnO nanorods were examined by fabricating n-ZnO/p-Si heterojunction assembly and the I-V characteristics of the fabricated heterojunction assembly were investigated at different temperatures. The fabricated n-ZnO/p-Si heterojunction diodes exhibited a turn-on voltage of ~5 V at different temperatures with a mean built-in-potential barrier of 1.12 eV. Moreover, the high values of quality factor obtained from I-V analysis suggested a non-ideal behavior of Schottky junction. PMID- 26373064 TI - Preparation and Characterization of Methylene Blue-Incorporated Folate Functionalized Fe3O4/Mesoporous Silica Core/Shell Magnetic Nanoparticles. AB - In the present work, a multifunctional nanomaterial, methylene blue-incorporated folate-functionalized Fe3O4/mesoporous silica core/shell magnetic nanoparticles, has been developed. Firstly, highly biocompatible monodisperse superparamagnetic Fe3O4@mSiO2 core/shell nanoparticles with mesoporous silica shells were synthesized. Then these particles were coated with the covalently bonded biocompatible polymer poly(ethylene glycol) (PEG) and modified with the cancer targeting ligand folic acid (FA). Finally, the water-soluble photosensitizer methylene blue (MB) was loaded into the mesoporous silica shell. Systematic experiments were performed to carefully evaluate the physical and chemical properties, cytotoxicity and cellular uptake of the multifunctional nanomaterial. PMID- 26373065 TI - Antibacterial Studies and Effect of Poloxamer on Gold Nanoparticles by Zingiber Officinale Extracted Green Synthesis. AB - Poloxamer finds excellent clinical and therapeutic uses for curing of various ailments. The Zin- giber officinale (Z. officinale) is one of the well-known medicinal plants. The poloxamer188 and the rhizome extract of Z. officinale have been used to synthesize the gold nanoparticles (AuNPs) by a green approach. The Z. officinale extract has been used as a reducing agent while the polox- amerl88 has been used as a stabilizing agent. The effect of addition of poloxamer on the controlling the shape and size of the AuNPs has been investigated by transmission electron microscopy (TEM) and dynamic light scattering techniques. The formation of AuNPs has also been confirmed by UV-Visible spectral, energy dispersive X-ray (EDX) and powder X-ray diffraction (XRD) analyses. The anti-bacterial activity of the green synthesized AuNPs has been investigated on the three human pathogens Staphylococcus aureus, Escherichia coli, and Klebsiella pneumonia. The poloxamer188 protected AuNPs inhibit the bacterial growth more effectively than the pure Z. officinale extract and the standard tetracycline (TA). PMID- 26373066 TI - Hydrostatic Extrusion and Nano-Hardness of Nanocrystalline Grade 2 Titanium. AB - The structure and corrosion resistance of Grade 2 titanium subjected to the hydroextrusion processes were examined. The microstructure was characterized using optical microscopy and transmission electron microscopy. The corrosion resistance was determined using the impedance and potentiodynamic methods, in 0.1 M H2SO4 solutions and an acidified 0.1 M NaCl solution with a pH of 4.2, at ambient temperature. Nanohardness tests were performed under a load of 100 mN. It has been demonstrated that the hydroextrusion method makes it possible to obtain relatively homogeneous nanocrystalline titanium Grade 2 with an increased hardness, the elastic modulus almost unchanged with respect to that of the initial structure and a lower corrosion resistance. PMID- 26373067 TI - Detection of Organic Vapors Based on Photoluminescent Bragg-Reflective Porous Silicon Interferomete. AB - Novel photoluminescent Bragg-reflective porous silicon, exhibiting dual optical properties, both the optical reflectivity and photoluminescence, was developed and used for sensing organic vapors. Photoluminescent Bragg-reflective porous silicon samples were prepared by an electrochemical etch of n-type silicon under the illumination. The etching solution consisted of a 3:1 volume mixture of aqueous 48% hydrofluoric acid and absolute ethanol. The typical etch parameters for the generation of photoluminescent Bragg-reflective porous silicon involved a periodic square wave current with 50 repeats. The surface of photoluminescent Bragg-reflective porous silicon was characterized by a FT-IR spectroscopy. Both reflectivity and photoluminescence were simultaneously measured under the exposure of organic vapors. The shift of reflection band to the longer wavelength and the quenching of photoluminescence under the exposure of various organic vapors were observed. PMID- 26373068 TI - Green Fabrication of Ag Coated Polyacrylonitrile Nanofibrous Composite Membrane with High Catalytic Efficiency. AB - Ag-coated polyacrylonitrile (PAN) nanofibers have been prepared by a novel, facile and green way that combined electrospinning technique and poly(dopamine) assisted electroless plating method. Poly(dopamine) (PDOP) was formed by oxidation polymerization of dopamine on the surface of PAN nanofibers to promote the electroless plating of silver. Scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), attenuated total reflectance Fourier transform infrared (ATR FT-IR) spectroscopy and energy dispersive X-ray spectroscopy (EDS) were used to characterize the morphology and structure of Ag/PDOP/PAN nanofibrous composite mem- brane and Ultraviolet-visible (UV-vis) Spectroscopy was used to investigate its catalytic performance. The results indicated that silver clusters composed of face-centred cubic crystal Ag with average crystallite size of about 18 nm were well distributed on the surface of dopamine-modified electrospun PAN nanofibers (PDOP/PAN). The prepared silver coated PDOP/PAN (Ag/PDOP/PAN) nanofibrous composite membrane exhibited an outstanding catalytic performance, and showed good reusabil- ity for completely degradating methylene blue (MB) dyes and reducing o-nitroaniline very quickly, respectively. PMID- 26373069 TI - Research on the Electrochemical Performance of Rutile and Anatase Composite TiO2 Nanotube Arrays in Lithium-Ion Batteries. AB - Titanium dioxide is considered as an ideal anode material for lithium-ion batteries. It has many different polymorphs such as anatase and rutile, etc. Both nano-scale rutile and anatase exhibit large potential in accommodating Li ions. Although the electrochemical performance of the rutile or anatase has been studied very well, their combined effect in lithium battery is still unclear at present. In our work, a kind of rutile and anatase composite TiO2 nanotube arrays was synthesized by two steps: anodization and heat treatment. The characteristics of the composite arrays were examined by XRD, SEM, and TEM. The first discharge capacity and charge capacity at 0.1 C (1C = 335 mA h g(-1)) of the composite is about 230 mA h g(-1), and 210 mA h g(-1), which are higher than pure anatase of 180 mA h g(-1) and 173 mA h g(-1). The composite remain about 80% of its initial capacities (185 mA h g(-1)) after 100 cycles. Two anodic peaks around 1.8 V and 2.2 V can be found in the composite in the cyclic voltammetry curves, while there is only one anodic peak in anatase. The separation of anodic and cathodic peak potentials of composite is less than that of anantase, indicating a better charge/discharge reversibility. The electrochemical impedance spectrum test shows the resistance of the composite is larger than that of pure anatase due to that the composite have more grain boundaries. The higher specific capacities of composite arrays may ascribe to the rutile's larger amount of lithium ions insertion and the defects facilitate lithium ions migration. Our work demonstrates that a better electrochemical performance of TiO2 can be achieved by synthesizing the composite material. PMID- 26373070 TI - Microstructure and Mechanical Properties of Nanostructured 1050/6061 Aluminum Alloy Fabricated by Four-Layer Stack Accumulative Roll-Bonding. AB - An ultrafine grained AA1050/AA6061 Al alloy sheet was successfully fabricated by four-layer stack ARB process. The ARB of AA1050 and AA6061 alloy sheets was performed up to 3 cycles without a lubricant at ambient temperature. The sample fabricated by the ARB was a multi-layer aluminum alloy sheet in which AA1050 and AA6061 layers are alternately stacked. The layer thickness of the each alloy became thinner and elongated to the rolling direction with increasing the number of ARB cycles. The tensile strength increased with the ARB, it reached about 347 MPa which is almost 2.4 times that of the starting material. The grain size decreased with increasing of the number of ARB cycles, became about 190 nm in thickness after 3 cycles. The variation of mechanical properties with the ARB was similar to those of the other ARB processed materials. However, the texture development was different from those of the conventional ARB processed materials. PMID- 26373071 TI - Numerical Study on Organic Light Emitting Diodes with Distributed Bragg Reflector. AB - In this paper, we report a theoretical study on the electronic-optical properties of the organic light emitting diodes (OLEDs) devices having a multilayer structure which consists of N,N'- bis(3-methylphenyl)-N,N'-bis(phenyl)benzidine (TPD) as a hole transport layer (HTL) and tris(8-hydroxyquinolinato)aluminum (Alq3) as an electron transport layer (ETL). We investigated the angular dependence of the light density of emission as well as CIE chromaticity for devices with and without a distributed Bragg reflector (DBR) between the ITO and the glass wherein the DBR comprise two species of materials with different refractive indices. Our simulation revealed that the insertion of the bottom mirror plays a critical role for the improvement of in the emission efficiency of 17% and the sharper emission characteristics. We found out that the chromaticity as well as the viewing angle improved with the presence of the bottom mirror. PMID- 26373072 TI - Ultra-High Speed Fabrication of TiO2 Photoanode by Flash Light for Dye-Sensitized Solar Cell. AB - In this work, a new way to fabricate nanoporous TiO2 photoanode by flash light is demonstrated. TiO2 nanoparticles are sintered on FTO glass by flash light irradiation at room temperature in ambient condition, which is dramatically simple, ultrahigh speed and one-shot large area fabrication process compared to a conventional high temperature (120 degrees C) thermal sintering process. The effect of the flash light conditions (flash light energy, pulse numbers and pulse duration) on the nanostructures of sintered TiO2 layer, was studied and discussed using several microscopic and spectroscopic characterization techniques such as SEM, FT-IR, XRD and XPS. The sintered TiO2 photoanodes by flash light were used in DSSC and its performance were compared with that of DSSC fabricated by conventional thermal sintering process. It was found that a flash light sintered TiO2 photoanode has efficiency which is similar to that of the thermal sintered photoanode. It is expected that the newly developed flash light sintering technique of TiO2 nanoparticles would be a strong alternative to realize the room temperature and in-situ sintering of photoanode fabrication for outdoor solar cell fabrication. PMID- 26373073 TI - Gold Nanoparticles-Poly(N-isopropylacrylamide) Composites Exhibiting Optically Induced Reversible Properties. AB - A very simple synthetic method is proposed to prepare spiky gold nanoparticles possessing a strong and broad absorption band around the surface of temperature sensitive poly(N-isopropylacrylamide), poly(NIPAM), particles. The structural properties of the composite particles were thoroughly characterized by UV-visible spectrophotometer, scanning electron microscope, and dynamic light scattering. These composite materials exhibited a reversible swelling and collapsing behavior above and below the lower critical solution temperature. As the surface-adsorbed spiky gold nanoparticles around the poly(NIPAM) possessed a strong and broad absorption band and exhibited the photon-to-heat conversion property, these nanocomposites also showed fast reversible structural diameter changes upon exposure to a broad band light. These types of composite particles may serve as an excellent template for the development of photothermally triggered carrier systems. PMID- 26373074 TI - Electrochemical Sensing of Dopamine, Uric Acid and Ascorbic Acid Using tRGO-TiO2 Nanocomposites. AB - This work reports a graphene-based nonenzymatic electrochemical sensing platform for the detection of dopamine (DA), uric acid (UA), and ascorbic acid (AA). Graphene oxide, synthesized by modified Hummers method, was thermally reduced in an induction furnace at 200 degrees C in an Ar-H2 atmosphere to obtain thermally reduced graphene oxide (tRGO). Nanocomposites of tRGO-TiO2 were obtained by a hydrothermal method, and were characterized using Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HRTEM), and X-ray diffraction (XRD). FTIR spectra showed Ti-O-C peaks, indicating covalent linkage between the TiO2 nanoparticles and the reduced graphene oxide sheets. Glassy carbon electrode (GCE) was modified with the nanocomposite (tRGO-TiO2-GCE), and the modified electrode could detect dopamine (DA: 1 to 1000 uM), uric acid (UA: 1 to 900 uM), and ascorbic acid (AA: 10 to 1000 uM) in each other's presence over wide ranges, with adequate separation in peak potentials. Differential pulse voltammetry experiments yielded linear responses with sensitivities of 133.18, 33.96, and 155.59 uA mM(-1) cm(-2) for DA, UA, and AA, respectively. PMID- 26373075 TI - Air-Hybrid Distributed Bragg Reflector Structure for Improving the Light Output Power in AlGalnP-Based LEDs. AB - We investigated air gap-induced hybrid distributed Bragg reflectors (AH-DBRs) for use in high brightness and reliable AlGalnP-based light emitting diodes (LEDs). An air gap was inserted into the side of DBRs by selectively etching the Al(x),Ga1-xAs DBR structures. With the AH-DBR structures, the optical output power of LEDs was enhanced by 15% compared to LEDs having conventional DBRs, due to the effective reflection of obliquely incident light by the air gap structures. In addition, the electrical characteristics showed that the AH-DBR LED is a desirable structure for reducing the leakage current, as it suppresses unwanted surface recombinations. PMID- 26373076 TI - Synthesis and Photoluminescent Properties of Nanorod Bundle Ln4O(OH)9NO3:Eu(Ln = Y, Lu) Prepared by Hydrothermal Method. AB - Well-crystallized nanorod bundles Ln4O(OH)9NO3:1%Eu(Ln = Y, Lu) have been successfully prepared by hydrothermal method. The crystalline phase, size and optical properties were characterized using powder X-ray diffraction (XRD), field emission-scanning electron microscopy (FE-SEM), infrared (IR) spectrograph and photoluminescent (PL) spectra. Site occupations of Eu3+ in crystals Ln4O(OH)9NO3:Eu(Ln = Y, Lu) were discussed based on excitation spectra and the empirical relationship formula between the charge transfer (CT) energy and the environmental factor. The emission spectra exhibited that the strongest emission peaks with an excitation wavelength of 395 nm were at 617 and 626 nm in crystal Lu4O(OH)9NO3:1%Eu and Y4O(OH)9NO3:1%Eu, respectively, both of which come from 5D0 7F2 transition of the Eu3+ ions. The broad excitation peaks at about 254 and 255 nm were found when monitored at 617 and 628 nm in crystal Lu4O(OH)9NO3:1%Eu and Y4O(OH)9NO3:1%Eu, respectively, which were due to O-Eu CT transition. Based on the dielectric theory of complex crystal, the CT bands at about 254 and 255 nm in Ln4O(OH)9NO3:1%Eu(Ln = Y, Lu) were assigned to the transition of O-Eu at Ln3(Ln = Y, Lu) site, from which we can conclude that Eu3+ ions occupied the site of Ln3(Ln = Y, Lu) in crystal Ln4O(OH)9NO3:1%Eu(Ln = Y, Lu). It put forward a new route to investigate site occupation of luminescent center ions in rare earth doped complex inorganic luminescence materials. PMID- 26373077 TI - Photoluminescence Enhancement of Silole-Capped Silicon Quantum Dots Based on Forster Resonance Energy Transfer. AB - Photoluminescent porous silicon were prepared by an electrochemical etch of n type silicon under the illumination with a 300 W tungsten filament bulb for the duration of etch. The red photoluminescence emitting at 650 nm with an excitation wavelength of 450 nm is due to the quantum confinement of silicon quantum dots in porous silicon. HO-terminated red luminescent PS was obtained by an electrochemical treatment of fresh PS with the current of 150 mA for 60 seconds in water and sodium chloride. As-prepared PS was sonicated, fractured, and centrifuged in toluene solution to obtain photoluminescence silicon quantum dots. Dichlorotetraphenylsilole exhibiting an emission band at 520 nm was reacted with HO-terminated silicon quantum dots to give a silole-capped silicon quantum dots. The optical characterization of silole-derivatized silicon quantum dots was investigated by UV-vis and fluorescence spectrometer. The fluorescence emission efficiency of silole-capped silicon quantum dots was increased by about 2.5 times due to F6rster resonance energy transfer from silole moiety to silicon quantum dots. PMID- 26373078 TI - Enhancement of the Luminance Efficiency in Organic Light-Emitting Devices with p Substituted Phenylphosphonic-Acid Self-Assembled Monolayers. AB - Organic light-emitting devices (OLEDs) containing self-assembled monolayers (SAMs) prepared by using p-substituted phenylphosponic acids on indium-tin-oxide electrodes were fabricated and examined to understand the substituent effect of the SAMs on the device performance. OLEDs modified by using (4 methoxyphenyl)phosphonic acid (MOPPA) SAMs or (4-chlorophenyl)phosphonic acid (CPPA) SAMs, both with electron withdrawing groups, had enhanced hole injection, reduced operating voltage, and remarkably increased current density and luminance efficiency compared with those without SAMs. The luminance efficiency which was the ratio of luminous flux to power for OLEDs containing CPPA SAMs and that for the OLEDs containing MOPPA SAMs were enhanced 2.2 and 1.9 times, respectively, in comparison with that of OLEDs without SAMs. CPPA SAMs significantly reduced the operating voltage of OLED by 24.8% compared with OLEDs without SAMs. PMID- 26373079 TI - Effect of Poly-TPD Molecular Weight on the Characteristics of Quantum-Dot Light Emitting Devices. AB - We have investigated the effect of poly-TPD molecular weight (Mw) on the characteristics of CdSe/ZnS quantum-dot light-emitting devices (QD-LEDs). The poly-TPDs with Mw = 24000 and 84000 were used for hole-transporting layer. The Mw = 24000 poly-TPD layer was seriously dissolved by toluene which was used for the dispersion of QDs, resulting in substantial thickness reduction during the spin coating of QD layer. The emission, external quantum efficiency, and driving characteristics of the QD-LEDs were investigated. A maximum external quantum efficiency of 2.1% was obtained in the QD-LED with Mw = 84000 poly-TPD layer. PMID- 26373080 TI - Fabrication and Characterization of Thermoelectric CrSi2 Compound by Mechanical Alloying and Spark Plasma Sintering. AB - A mixture of elemental Cr-Si powders has been subjected to mechanical alloying (MA) at room temperature to prepare CrSi2 thermoelectric compound.The MA powders were sintered at 800-1000 degrees C Cunder 60 MPa using spark plasma sintering (SPS) technique. Due to the observed larger loss of Si relative Cr during ball milling, the starting composition was modified to Cr30Si70, Cr31.5Si68.5 and Cr33Si67 to get a single phase of CrSi2 compound. The single phase CrSi2 has been obtained by MA of Cr31.5Si68.5 mixture powders for 70 h and subsequently sintered at 1000 degrees C. X-ray diffraction data shows that the SPS compact sintered at 1000 degrees C consists of only nanocrystalline CrSi2 compound with a grain size of 250 nm. The value of Seebeck coefficient of CrSi2 compound increases with temperature and reaches maximum value of 245 uV/K at 300 degrees C. PMID- 26373081 TI - Synthesis and Luminescence Properties of Blue Na(Sr0.97-xCa(x))PO4:0.03Eu2+ Phosphors for White Light Emitting Diode Applications. AB - The crystal structure and luminescence properties of Na(Sr0.97-xCax)PO4:0.03Eu2+ (0 < x < 1.0) phosphors were studied, depending on the Ca2+ concentration. All the Na(Sr0.97-xCax)PO4:0.03Eu2+ phosphors had a hexagonal crystal structure. The excitation spectra of the prepared phosphors showed a broad band ranging from 250 to 420 nm, which arises due to the 4f-5d transitions of Eu2+ ions. Upon the excitation of 334 nm wavelength, the emission spectra showed a broad blue band ranging from 400 to 700 nm peaking at 450 nm. Among the prepared phosphors, the Na(Sr0.72Ca0.25)PO4:0.03Eu2+ showed the strongest emission intensity and could be applied as a blue emitting phosphor for UV-based w-LEDs. PMID- 26373082 TI - Photocatalytic Properties of Silver Core/Titania Shell Nano-Wires Grown on a Glass Substrate Using a Glycothermal Process Assisted by a Photochemical Reaction. AB - A silver core/titania shell nano-wire film was successfully prepared on a glass substrate via a glycothermal process that was assisted by a photochemical reaction using tetra-n-butyl titanate as the titanium source and silver nitrate as the silver source in an autoclave with ethylene glycol as a solvent. The morphology, diameter, length, and density of the core/shell nano-wires that were synthesized could be varied by changing the silver/titanium molar ratio of the starting materials. The samples produced were characterized by X-ray diffraction and scanning electron microscopy. The photocatalytic activity of the silver core/titania shell nano-wire film was investigated by measuring the photodegradation rate of rhodamine B in aqueous solution. PMID- 26373083 TI - Synthesis and Spectral Analysis of Head-to-Tail Shaped Ag2S/ZnS Near-Infrared Quantum Dots with Manganese Dopant. AB - Silver sulfide (Ag2S) near-infrared quantum dots have been synthesized by one pot process and the water solubility of the quantum dots was enhanced by ligand exchange. With the addition of zinc source, zinc sulfide (ZnS) nanocrystals grew like a link with the Ag2S in head-to-tail structure. Furthermore, in the presence of manganese dopants, particles exhibited twice the length of previous size. The optical and structural properties of these three kinds of quantum dots (Ag2S, Ag2S/ZnS, and Mn-doped Ag2S/ZnS) were characterized through photoluminescence spectra, UV-Vis absorption spectra, and transmission electron microscopy. It has been found that a linked structure is formed in ZnS-Ag2S-ZnS by manganese doping. PMID- 26373084 TI - A Facile Synthesis Routine of Ag2S-CdS Heterostructure Nanorods with Enhanced Trap Emissions. AB - We explored a facile routine to synthesize morphology-controlled Ag2S-CdS heterostructures. The heterostructures were achieved by a two-step method where CdS nanorods were prepared in the first step, acting as the substrates inducing successive cation exchange reaction between Cd2+ and Ag+ ion. The nucleation sites of Ag2S can be readily controlled by varying the feed ratios of Ag+ to Cd2+ ion, thus leading to formation of heterostructures with different morphology where Ag2S particles grow on the tips of the CdS rods, or at multiple locations across the nanorods. HRTEM analysis showed that Ag2S particles were grown on the varied sites of CdS rods with a coherent, quasi-epitaxial interface having different degrees of lattice mismatch. Photoluminescence results showed that, compared to bare CdS nanorods, enhanced trap emissions were observed after the growth of Ag2S particles on the rods, which can be attributed to the strained interfaces instead of impurities doping. PMID- 26373085 TI - Field Emission Lamps Prepared with Dip-Coated and Nickel Electroless Plated Carbon Nanotube Cathodes. AB - Fabrication and efficiency enhancement of tubal field emission lamps (FELs) using multi-walled carbon nanotubes (MWNTs) as the cathode field emitters were studied. The cathode filaments were prepared by eletrolessly plating a nickel (Ni) film on the cathode made of a 304 stainless steel wire dip-coated with MWNTs. The 304 wire was dip-coated with MWNTs and nano-sized Pd catalyst in a solution, and then eletrolessly plated with Ni to form an MWNT-embedded composite film. The MWNTs embedded in Ni not only had better adhesion but also exhibited a higher FE threshold voltage, which is beneficial to our FEL system and can increase the luminous efficiency of the anode phosphor. Our results show that the FE cathode prepared by dipping three times in a solution containing 400 ppm Pd nano catalysts and 0.2 wt.% MWNTs and then eletrolessly plating a Ni film at a deposition temperature of 60 degrees C, pH value of 5, and deposition time of 7 min has the best FE uniformity and efficiency. Its emission current can stay as low as 2.5 mA at a high applied voltage of 7 kV, which conforms to the high voltage-and-low-current requirement of the P22 phosphor and can therefore maximize the luminous efficiency of our FEL. We found that the MWNT cathodes prepared by this approach are suitable for making high-efficiency FELs. PMID- 26373086 TI - Improved Photo-Detection Using Zigzag TiO2 Nanostructures as an Active Medium. AB - Zigzag TiO2 nanostructures were fabricated using oblique angle deposition technique. The field emission gun-scanning electron microscope (FEG-SEM) image shows that the TiO2 zigzag nanostructures were ~500 nm in length. Averagely two times enhanced UV-Vis absorption was recorded for zigzag structure compared to perpendicular TiO2 nanowires. The main band transition was observed at ~3.4 eV. The zigzag TiO2 exhibited high turn on voltage (+11 V) than that of nanowire (+2 V) detector under dark which were reduced to +0.2 V and +1.0 V under white light illumination, respectively. A maximum ~6 fold photo-responsivity was observed for the zigzag TiO2 compared with nanowire device at + 1.0 V applied potential. The maximum photo-responsivity of 0.36 A/W at 370 nm was measured for the zigzag TiO2 detector. The TiO2 zigzag detector showed slow response with rise time of 10.2 s and fall time of 10.3 s respectively. The UV (370 nm) to visible (450 nm) wavelength rejection ratio of photo-responsivity was recorded ~4 times for the detector. PMID- 26373087 TI - Sub-Nanometer Controllable Fabrication of Freestanding Hetero-Structures Through Plasma-Matter Interaction During Ion Irradiation. AB - Freestanding three-dimensional nanostructures have attracted intense attention for their potential application in novel electronic, optical, magnetic, biological and mechanical devices. However, controlled fabrication of highly ordered, well-shaped and freestanding core-shell hetero-structures in large scale cost-effectively is still a challenge. Here we present the constructing of freestanding hetero-structures by taking advantages of lateral re-deposition, a phenomenon that occurred during plasma-matter interaction and usually to be minimized/avoided in conventional device fabrication. Various freestanding nanowires were irradiated under optimized conditions, in that upon etching, the sputtered species from the supporting substrates are re-deposited laterally onto the core material, mainly through plasma-phase interaction to form complex core shell structures. Factors, including the supporting substrate, plasma power, irradiation time and gas flow rate, were used to tune the properties of the desired structures. Pencil-like, conic and wing-shape free-standing hetero structures have been formed with controllable growth rate of sub-nanometer per minute across the width of the structure. The related mechanism was proposed. Our results indicate that such technique might be a potential approach for the fabrication of high aspect-ratio freestanding functional core-shell structures to construct mechanical, optical, biological and electrical devices. PMID- 26373088 TI - Investigation Into Gas-Sensing Mechanism of Nanostructured Magnesium Aluminate as a Function of Temperature. AB - In this study, we used a new simple chemical method to synthesise nanostructured magnesium aluminate (NMA) powder. Sol-gel technique followed by sonication was used to develop different sensor samples namely NMA573, NMA873, and NMA1 073 by calcination at temperatures of 573, 873, and 1073 K respectively. Average crystallite size of 18-27 nm and specific surface area of 68.09 to 61.84 m2 g(-1) was obtained for the sensor samples. The existence of functional groups at 800 and 550 cm-1 corresponding respectively to AIO6 group and the lattice vibration of MgO4 stretching were confirmed through FTIR studies; SEM/EDX confirm the spherical morphology with elemental composition Mg, Al and O at different calcination temperatures. UV-Vis absorption spectra show band gap energy as 3.50, 3.48, and 3.44 eV for the sensor samples NMA573, NMA873, and NMA1 073 respectively. The effect of polyethylene glycol on the gas-sensing behaviour was studied in all the sensor samples. In particular, NMA1073 was found to have better resistance and sensor response for CO gas than NMA573 and NMA873. The effect of increase in calcination temperature of the sensor samples on the structural, morphological, optical, and gas response properties were carried out extensively to explore its gas sensing applications. PMID- 26373089 TI - Low Surface Recombination Velocity on P-Type Cz-Si Surface by Sol-Gel Deposition of Al2O3 Films for Solar Cell Applications. AB - High quality surface passivation has gained a significant importance in photovoltaic industry for fabricating low cost and high efficiency solar cells using thinner and lower cost wafers. The passivation property of spin coated Al2O3 films with a thickness of about 50 nm on p-type Cz-Si wafers has been investigated as a function of annealing temperatures. An effective surface recombination velocity of 55 cm/s was obtained for the films annealed at 500 degrees C. The chemical and field effect passivation was analyzed by C-V measurements. A high density of negative fixed charges (Qf) in the order of 9 x 10(11) cm(-2) was detected in Al2O3 films and its impact on the level of surface passivation was demonstrated experimentally. The C-V curves show density of the interface state (Dit) of 1 x 10(12) eV(-1)cm(-2) at annealing temperature of 500 degrees C. During annealing, a thin interfacial SiOx is formed, and this interfacial layer is supposed to play a vital role in the origin of negative QF and Dit. The homogeneous SiOx interlayer result in higher passivation performance due to both the increase of negative Qf and the decrease of Dit. PMID- 26373090 TI - Iron Oxide (alpha-Fe2O3) Nanoparticles as an Anode Material for Lithium Ion Battery. AB - alpha-Fe2O3 nanoparticles were synthesized by facile hydrothermal process at low temperature and used as efficient anode material for the fabrication of lithium ion battery. The prepared nanoparticles were characterized in detail by various techniques such as X-ray diffraction pattern, field emission scanning electron microscopy (FESEM) combined with energy dispersive spectroscopy (EDS), transmission electron microscopy (TEM) equipped with high-resolution TEM, Fourier transform infrared (FTIR) and Raman-scattering spectroscopy. The detailed characterizations revealed that the nanoparticles are synthesized in large quantity and possessing well-crystalline rhombohedral alpha-Fe2O3 structure. For application point of view, the synthesized nanoparticles were used as an anode material for fabrication of Li-ion battery. A coin cell of type-2032 was assembled using as-synthesized alpha-Fe2O3 nanoparticles and its charge-discharge profile was analyzed. Interestingly, it was observed that the cell delivered the first-charge capacity of 870 mAh g(-1) and the cell delivered a discharge capacity of 1500 mAh g(-1) during its first cycle. PMID- 26373091 TI - Effect of Light Absorption in InGaN/GaN Vertical Light-Emitting Diodes. AB - For evaluating the effect of light absorption in vertically structured thin film light-emitting diodes (VLEDs), we investigate the dependence of the efficiencies on the several specific parameters including thickness and doping concentration (N(D)) of the n-GaN layer, a design of hetero-structures of the n-GaN layer, and a number of pairs of multi-quantum wells (MQWs). Generally, there is a complementary relation between internal quantum efficiency (IQE) and light extraction efficiency (LEE). However, we confirmed that LEE determined by light absorption is more dominant than IQE in VLED structures with a textured surface, from numerical simulation and experimental results. Effect of light absorption is more prominent in the vertical chip with a textured surface than in that with a flat surface, because a travel length of light extracted from the textured surface is longer. Minimizing light absorption in VLEDs is a key technology for improving light output, and light absorption speaks for the index of enhancement by the general technologies for improving LEE. PMID- 26373092 TI - Effect of Sapphire Substrate Thickness on the Characteristics of 450 nm InGaN/GaN Multi-Quantum Well Light-Emitting Diodes. AB - 450 nm InGaN/GaN multi-quantum well (MQW) ligth-emitting diodes (LEDs) prepared on sapphire substrate with different thicknesses were fabricated and characterized. By thinning the sapphire substrate to 50 um, it was found that the LED exhibited the highest light output power of ~48 mW under high injection current of 50 mA, improved by about 35% compared to that with 200 um-thick sapphire without increasing the operating voltage. The electroluminescence intensity was increased and the spectral peak wavelength was blue-shifted, because the wafer bowing-induced mechanical stress alters the piezoelectric field in the InGaN/GaN MQW active region of the LED. The internal quantum efficiency was also improved by about 10% at an injection current of 50 mA. Moreover, the external quantum efficiency and light extraction efficiency were optimized because of enhanced light output intensity. The results confirmed that sapphire substrate thinning effectively alters the piezoelectric field in the InGaN/GaN active region, and hence increases both of the effective band gap and the probability of radiative recombination. PMID- 26373093 TI - Fabrication of AIN Nano-Structures Using Polarity Control by High Temperature Metalorganic Chemical Vapor Deposition. AB - This study investigates the crystallographic polarity transition of AIN layers grown by high temperature metalorganic chemical vapor deposition (HT-MOCVD), with varying trimethylaluminum (TMAI) pre-flow rates. AIN layers grown without TMAI pre-flow had a mixed polarity, consisting of Al- and N-polarity, and exhibited a rough surface. With an increasing rate of TMAI pre-flow, the AIN layer was changed to an Al-polarity, with a smooth surface morphology. Finally, AIN nano pillars and nano-rods of Al-polarity were fabricated by etching a mixed polarity AIN layer using an aqueous KOH solution. PMID- 26373094 TI - Reverse Current Characteristics of InP Gunn Diodes for W-Band Waveguide Applications. AB - InP is considered as the most promising material for millimeter-wave laser-diode applications owing to its superior noise performance and wide operating frequency range of 75-110 GHz. In this study, we demonstrate the fabrication of InP Gunn diodes with a current-limiting structure using rapid thermal annealing to modulate the potential height formed between an n-type InP active layer and a cathode contact. We also explore the reverse current characteristics of the InP Gunn diodes. Experimental results indicate a maximum anode current and an oscillation frequency of 200 mA and 93.53 GHz, respectively. The current-voltage characteristics are modeled by considering the Schottky and ohmic contacts, work function variations, negative differential resistance (NDR), and tunneling effect. Although no direct indication of the NDR is observed, the simulation results match the measured data well. The modeling results show that the NDR effect is always present but is masked because of electron emission across the shallow Schottky barrier. PMID- 26373095 TI - High-Temperature Corrosion of Nano-Multilayered TiAISiN Thin Films in Ar-0.2%SO2 Gases. AB - Nano-multilayered TiAlSiN films with a composition of 26Ti-16.3Al-1.2Si-56.5N (at.%) were deposited onto steel via arc ion plating, and corroded at 800-900 degrees C for 30 h in Ar-0.2%SO2 gases. The films were corrosion resistant, because the oxidation process dominated sulfidation. The scales consisted primarily of Al2O3 and TiO2, where a small amount of Si dissolved. PMID- 26373096 TI - Photoluminescence Properties of Red-Emitting Ca3Sr3-x(PO4)4:xEu3+ Phosphors for White Light-Emitting Diodes. AB - The photoluminescent properties of the Eu(3+)-activated Ca3Sr3(PO4)4 phosphors prepared by a solution combustion method were investigated. The excitation spectra of Ca3Sr3-x(PO4)4:xEu3+ (0.05 <= x <= 0.6) phosphors under 614 nm wavelength showed a broad band centered at 266 nm along with other peaks at 320, 362, 381, 394, 414, 464, and 534 nm. The emission spectra observed in the range of 450 to 750 nm under excitation at 394 nm were ascribed to the 5D0-7F1-4 transitions of Eu3+ ions. The Ca3Sr3-x(PO4)4:xEu3+ phosphors showed the strongest red emission at 614 nm due to the electric dipole 5DO -->7F2 transition of Eu3+. The strongest emission intensity was obtained for the Eu3+ ions of x = 0.5. The prepared Ca3Sr3-x(PO4)4:xEu3+ can be used as an efficient red phosphor for UV based white LEDs. PMID- 26373097 TI - Fabrication Characterization of 1Ce10ScSZ Electrolyte Prepared by Co Precipitation and Hydrothermal Treatment for Solid Oxide Fuel Cells. AB - Nanocrystallite ceria-doped scandia-stabilized zirconia (1Ce10ScSZ) powders are prepared using a combination of co-precipitation and hydrothermal treatments. Power density of 1.0 W cm(-2) is obtained at 1.6 A cm(-2) and 800 degrees C due to the drastic reduction of ohmic and polarization resistance in the SOFC cell. PMID- 26373098 TI - Characteristics of the Mg-Doped Cr-Deficient CuCr0.95Mg0.02O2 Thin Films Prepared by Using Pulsed Laser Deposition. AB - 2 at% Mg doped thin films of delafossite CuCrO2 and Cr-deficient CuCr0.97O2 were prepared by pulsed laser deposition. The films were grown on c-sapphire single crystal substrates at a range of substrate temperatures, and the effects of the processing parameters on thin film properties were examined. The crystallinity improved with increasing substrate temperature and Mg-doping. The substitution of Mg in the CuCrO2 and Cr-deficient CuCr0.97O2 thin films increased the electrical conductivity significantly with a slight decrease in optical transmittance. By introducing Mg-doping to Cr-deficient CuCr0.97O2 thin films, a CuCr0.95Mg0.02O2 thin film with an electrical conductivity of 29.63 S/cm and a mean optical transmittance of 60% was fabricated. PMID- 26373099 TI - Formation and Characterization of Ni Nanofiber Catalysts on Nickel Metallic Foam by Electrospinning Process. AB - We report the fabrication of nickel nanofiber catalysts supported on nickel metallic foam using a modified electrospinning with a grounded rotor and sequential reduction process. The robust deposition of aligned Ni nanofibers with a uniform morphology on the highly porous surfaces of the metallic foam could be achieved by controlling electrospinning parameters such as applied voltage, tip collector-distance (TCD), concentration of polymer, and humidity. The diameters of the obtained nanofibers decreased with increasing voltage and TCDs. The uniform and thinnest Ni nanofibers on the Ni foam were obtained at a humidity of less than 30%, 15 kV applied voltage, and 17 cm TCD when using a precursor composed of nickel nitrate salt and poly(vinyl) pyrrolidone. The Ni foam catalyst support exhibited the superior thermal conducting property than other supports of MgO-MgAl2O4, Al2O3, and SiC, enabling to a higher heat transfer during catalytic reaction. As a result, the Ni nanofiber catalyst with a high surface area and superior heat transfer performance, which is supported on the metallic foam, were successfully fabricated via a modified electrospinning for potential application of XTL process converting anything to liquids, such as for Gas-to-Liquid (GTL), Coal-to-Liquid (CTL), and Biomass-to-Liquid (BTL). PMID- 26373100 TI - Directional Terahertz Radiation from GalnP Lateral Superlattice. AB - We devised directionally controllable THz emission sources based on lateral composition modulation (LCM) structures. LCM structures were composed of In-rich Ga0.47In0.53P and Ga-rich Ga0.51In0.49P layers whose period was in quantum scale of ~'5 nm. The inherent type II band alignment in these structures leads to electron-hole (e-h) separation and plays a key role in generating later- ally polarized dipole ensembles, thus concomitantly emitting enhanced transmissive THz waves as compared to bulk sample. On the other hand, in lateral geometry, changes in THz fields between LCM and bulk structures turned out to negligible since the vertical electronic diffusion was allowed in both samples. PMID- 26373101 TI - Facile Synthesis of Carboxylic Functionalized MFe2O4 (M = Mn, Co, Zn) Nanospheres. AB - A facile one-pot solvothermal method was developed for the synthesis of carboxylic functionalized MFe2O4 (M = Mn, Co, Zn) nanospheres. Field-emission scanning electron microscopy, X-ray powder diffraction, Fourier transform infrared spectrometer, and a superconducting quantum interference device magnetometer were used to characterize the morphologies, compositions and properties of the functionalized materials. Results show that all of the products were cubic spinel structures and exhibited hierarchical sphere-like morphologies, which were composed of primary nanocrystals. The MFe2O4 present advantageous functionality and good water dispensability due to the preferential exposure of uncoordinated carboxylate groups on their respective surfaces. These properties make them ideal candidates for various important applications such as drug delivery, bioseparation, and magnetic resonance imaging. PMID- 26373102 TI - Critical Shear Stress of Rhodium Nanocontacts Studied by In Situ High-Resolution Transmission Electron Microscopy. AB - The structural dynamics during tensile deformation of rhodium (Rh) nanocontacts (NCs) at room temperature was observed by in situ high-resolution transmission electron microscopy. The critical shear stress for a {111}-(110) slip system was estimated from simultaneous measurement of the force acting on the NCs. It was found that the critical shear stress increased to ~5 GPa, which was comparable with that for a homogeneous slip, as the minimum cross-sectional width of the NCs decreased to less than 1.6 nm. This result implies that the slip mechanism in Rh transformed from dislocation-mediated slip to homogeneous slip when the width decreased to less than the critical size. PMID- 26373103 TI - Effect of Surface Modification on Cellular Internalization of Fe3O4 Nanoparticles in Strong Static Magnetic Field. AB - Magnetic nanoparticles (MNPs) controlled by alternating mangetic field (AMF) are widely investigated in biomedical applications, while the effects of strong static magnetic field (SMFs) on mammalian cells with MNPs for drug-delivery, magnetic resource imaging and magnetofection have been evaluated poorly. Although surface modifications provide a suitable system for expanding the bioapplication of MNPs, the viability and the cellular internalization of modified MNPs which stands for their biocompatibility and efficiency in application need to be examined urgently. In present study, human lung cancer cells (A549), a well-known epithelial cell model for drug metabolism research, were used to evaluate the effects of strong SMFs on cellular internalization and cell viability of Fe3O4 MNPs modified by chitosan, dextran, polyacrylamide, polyethylene glycol, phosphatidylcholine, cationic-charged and anionic-charged. The cationic-charged and phosphatidylcholine-coated Fe3O4 MNPs could increase the cellular uptaken in a dose dependent manner and the particles caused a vacuolar appearance in A549 cells. With exposure to 8.5 T SMF, the assay of ATP content showed that anionic charged and phosphatidylcholine-coated Fe3O4 MNPs changed the energy metabolism of A549 cells, which might be consistent with the observation in cellular internalization. The cell viability and proliferation of A549 cells were all slightly affected by various modified MNPs with or without 8.5 T SMF exposure. PMID- 26373104 TI - Hierarchical Honeycomb Anatase TiO2 with (100) Facet: Facile Hydrothermal Preparation and Enhanced Photocatalytic Performance. AB - Hierarchical honeycomb anatase TiO2 with (100) facet was synthesized by using a facile hydrothermal method. The product was characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HRTEM) and UV-Vis diffused reflectance spectroscopy (DRS), respectively. The photocatalytic activity of the product was investigated on the degradation of Rhodamine B (RhB). It was found that the absorptive wavelength edge of the product was 400 nm, which shifted to the red light compared to the ordinary anatase TiO2. The anatase TiO2 honeycomb, which was comprised from curling nanoflake, exhibited excellent photocatalytic performance. Under the simulate sunlight irradiation for 20 minutes, the degradation rate of RhB nearly reached 80%. And after being irradiated for 40 minutes, the degradation rate reached 99.0%, close to decomposing completely. It indicated that the photocatalytical activity of honeycomb anatase TiO2 was better compared to P25 and it would be widely used in industrial application and environmental remediation. PMID- 26373105 TI - Improving the Cycling Stability of Si/Ni Negative Composite Through Introducing the SiOC Skeleton. AB - A Si/Ni/SiOC (SNS) composite structure with high efficiency and long-term cycling stability was synthesized by a cost-effective and scalable method. In this structure, a SiOC net with favorably physical and chemical stability acts as a skeleton to support and segregate Si-Ni mixed powders. The electrochemical performance of Si-Ni as a negative for Li-ion battery had been largely improved through introducing a stable SiOC skeleton structure as buffer base. Compared with Si-Ni mixed powders, the SNS composite negative exhibits excellent long-term cycling stability and capacity. Such SNS composite negative shows excellent cycling stability with a specific capacity of 505.5 mA. h . g(-1) and 84% capacity retention over 25 cycles at 0.2 C rate, which has the perspective application in the future high energy density li-ion batteries. In the meantime, the design and fabrication of this structure has the potential to provide a way for the other functional composite materials in the semiconductive field. PMID- 26373106 TI - The Effect of Acid Treatment and Reactive Temperature on the Formation of TiO2 Nanotubes. AB - TiO2 nanotubes (TNTs) were synthesized by a hydrothermal method from commercial TiO2 in NaOH followed by HCl washing. The samples were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmitting electron microscopy (TEM), and Brunauer-Emmet-Teller (BET) measurements. The untreated acid samples (pH ~ 12) don't appear nanotubes structure, while acid-treated samples until the pH reached around 2 have approximate diameters of nanotubes of 10 nm. The samples reaction temperature at 135 degrees C appear nanotubes structure while the samples reaction temperature at 150 degrees C have combination of the nanotubes and the samples treatment temperature at 170 degrees C appear both nanotubes structure and particles clumping together. The surface area of the TNTs was 83,5 m2/g while the surface area of commercial TiO2 particles was 41 m2/g. PMID- 26373107 TI - Free-Standing Polyimide Nanotips on Substrates for Preparation of Hollow TiO2 Nanotips. AB - We report a facile method to fabricate free-standing polyimide (PI) nanotips on substrates by using plasma treatment with oxygen gas. The PI nanotips were prepared from the self-organization of unetchable materials deposited on a PI film during the plasma treatment. This approach provides a single-step process for the preparation of polymer nanotips in a large area (>inch scale). Furthermore, a selective patterning of the PI nanotips in a specific area was achieved by using a shadow mask. Due to excellent thermal resistance of PI, the PI nanotips maintained structural integrity at high temperature (~ 300 degrees C). To demonstrate potential application of PI nanotips as a template for hollow nanostructures, hollow TiO2 nanotips were prepared after atomic layer deposition of TiO2 followed by the burning of PI layer. PMID- 26373108 TI - Enhancement of Device Performances in GaN-Based Light-Emitting Diodes Using Nano Sized Surface Pit. AB - We report the improvement in optical and electrical properties of GaN-based green light-emitting diodes (LEDs) with nano-sized etch pits formed by the surface chemical etching. In order to control the density and sizes of etch pits formed on top surface of green LEDs, H3PO4 solution is used as a etchant with different etching time. When the etching time was increased from 0 min to 20 min, both the etch pit size and density were gradually increased. The improvement of extraction efficiency of LEDs using surface etching method can be attributed to the enlarged escape angle of generated photon by roughened p-GaN surface. The finite difference time-domain (FDTD) simulation results well agreed with experimentally observed results. Moreover, the LED with etched p-GaN surface for 5 min shows the lowest leakage current value and the further increase of etching time resulting in increase of densities of the large-sized etch pit makes the degradation of electrical properties of LEDs. PMID- 26373109 TI - Improvement of the Light Extraction Efficiency of InGaN/GaN Blue Light Emitting Diodes Using ZnO Nanostructures. AB - Herein, we report the effects of geometric morphology of ZnO nanostructures on the extraction efficiency of GaN-based light emitting diodes (LEDs). We performed numerical analysis based on the two-dimensional (2D) finite difference of time domain (FDTD) method that was utilized to calculate the light extraction efficiency of the LEDs. We found that the extraction efficiency of the LED increased upon changing the shape of ZnO nanostructure from nanorods to pencil likenanorods. The current-voltage characteristics of the LED with ZnO nanorods or pencil-like nanorods were similar to those of the LED that did not contain any ZnO nanostructures. The light output power of the LEDs containing ZnO nanorods or pencil-like nanorods at 100 mA increased additionally to 28% and 39%, respectively, relative to that of the LED that did not contain any ZnO nanostructures. These results confirm that the geometric morphology of the ZnO nanostructure plays an important role in improving the extraction efficiency of the LEDs. PMID- 26373110 TI - Luminance Mechanisms of White Organic Light-Emitting Devices Fabricated Utilizing a Charge Generation Layer with a Light-Emitting Function. AB - The luminance mechanisms of the white organic light-emitting devices (WOLEDs) with a charge generation layer (CGL) consisting of a tungsten oxide layer and a 5,6,11,12-tetraphenyltetracene (rubrene) doped N,N',-bis-(1-naphthyl)-N,N' diphenyl1-1'-biphenyl-4,4'-diamine (NPB) layer were investigated. Current densities and luminances of the WOLEDs increased with increasing a rubrene doping concentration because the formation of excitons in the rubrene-doped NPB layer increased due to the more exciton trapping in rubrene molecules and the delay of the electron injection due to the insertion of the litium qunolate layer. The yellow light emitted from the rubrene-doped NPB layer in the CGL combined with the blue light from the main emitting layer of the WOLEDs, resulting in the emission of the white light. The ratio between the yellow and the blue color peak intensities of the electroluminescence spectra for the WOLEDs was controlled by the rubrene doping concentration. The Commission Internationale de l'Eclairage coordinates of the fabricated WOLED were (0.31, 0.42) at 740.7 cd/m2, indicative of white emission color. PMID- 26373111 TI - Synthesis of ZnS Microspheres by Template-Free Hydrothermal Method for Photocatalytic Reaction. AB - In this work, ZnS microspheres consisting of nanoblocks were synthesized by a simple, template-free approach employing a hydrothermal reaction at different temperatures, using Zn(CH3COO)2 and Na2S2O3 . 5H2O as starting materials in the aqueous solution. The synthesized samples were characterized using field-emission scanning electron microscopy (FE-SEM), X-ray diffraction (XRD), and Brunauer Emmett-Teller (BET). The photocatalysts were evaluated using photodecomposition of methylene blue under UV-C light. The photocatalytic degradation rate followed a pseudo-first-order equation. The kinetic constant (k1) of the ZnS microspheres was 5.43 x 10(-2) min(-1). PMID- 26373112 TI - Effect of Al Doping on Optical Band Gap Energy of Al-TiO2 Thin Films. AB - Al-TiO2 thin films were prepared using a sol-gel derived spin coating by varying the Al/Ti molar ratio from 0 to 0.73 to investigate the effect of Al doping on the optical band gap energy (Eg) of the films. GAXRD results indicated that Al TiO2 is composed of anatase and FTO phases when the Al/Ti molar ratio was less than 0.18. Above 0.38, no other peaks except FTO were found and transparency of the films was severely deteriorated. Eg of Al-TiO2 decreased from 3.20 eV to 2.07 eV when the Al/Ti ratio was raised from 0 to 0.38. Eg of 2.59 eV was found for the anatase Al-TiO2 films having the Al/Ti ratio of 0.18. The absorption band of Al-TiO2 coatings shifted dramatically from the UV region to the visible region with increasing the amount of Al dopant. The Al doping was mainly attributed to the optical band gap energy of Al-TiO2. PMID- 26373113 TI - Growth Behavior of High Density Al2O3 Layer Prepared by Using Cyclic Chemical Vapor Deposition Technology. AB - In this paper, growth behavior of high density Al2O3 which was prepared by using cyclic chemical vapor deposition (C-CVD) system has been systematically investigated. Tri-Methyl-Aluminum (TMA) and oxygen (02) plasma was used as source precursor and reactant, respectively. Unlike the conventional ALD system that source precursor and reactant was injected alternatively that was separated by inert gas purge step, TMA and 02 was mixed and co-fed into the process chamber simultaneously, followed by purge step. To obtain high density and defects-free Al2O3 layer, source precursor feeding time and the number of deposition cycles dependence on the thickness of C-CVD grown Al2O3 layer were investigated. We found that thickness of Al2O3 layer was increased almost linearly as the number of cycles increased which are typical characteristics of CVD. On the other hand, self-limiting phenomenon was observed in thickness as source feeding time increased which showed saturation of the thickness as source feeding time further increased. Using the optimized C-CVD process conditions, density of 3.298 g/cm3 was obtained in 100 nm thick Al2O3 layer whereas that of ALD Al2O3 was 3.192 g/cm3. The C-CVD grown Al2O3 layer effectively prevents water vapor from diffusing into active layer of organic light emitting diodes, which shows C-CVD grown Al2O3 layer can be applied to water vapor permeation barrier layer in organic light emitting diodes. PMID- 26373114 TI - Blue Fluorescent Materials Composed of Anthracene-Aryl Amine-Anthracene Derivatives for Organic Light-Emitting Diodes. AB - Blue fluorescent emitters based on anthracene-aryl amine-anthracene derivatives were studied for efficient OLEDs. Compound 1 exhibited efficient EL propereties with luminous and power efficien- cies of 4.50 cd/A and 1.75 lm/W at 200 mA/cm2, respectively and CIE coordinates of (0.18, 0.26) at 7.0 V. PMID- 26373115 TI - Blue Emitters Based on Anthracene-Aryl-Anthracene Moieties End-Capped with 1 Naphthyl Groups for Organic Light-Emitting Diodes. AB - We have designed emitters based on Anthracene-Aryl-Anthracene moieties end-capped with 1-naphthyl groups. In particular, a device showed blue EL properties with luminous and power efficiencies of 1.95 cd/A and 0.93 lm/W at 200 cd/m2 respectively, and CIE coordinates of (0.16, 0.10) at 7.0 V. PMID- 26373116 TI - Various Blue Emitting Materials Based on Pyrene Derivatives for Organic Light Emitting Diodes. AB - We designed and synthesized two pyrene derivatives: 1,6-di-1-naphthalenyl-pyrene (1) 1,6-Bis(10- phenyl-9-anthracenyl)-pyrene (2). Two OLED devices were fabricated in the following sequence: ITO (180 nm)/4,4'-bis(N-(1-naphthyl)-N phenylamino)bipheny (NPB) (50 nm)/Blue materials 1 and 2 (40 nm)/Tris(8 hydroxyquinolinato)aluminium (Alq3) (15 nm)/lithium quinolate (Liq) (2.0 nm)/Al (100 nm). Two devices showed efficient blue emissions. Particularly, a device using 2 as emitting material showed blue EL properties with luminous efficiencies of 3.19 cd/A, power efficiencies of 1.54 lm/W, quantum efficiency of 2.42% at 500 cd/m2 and CIEx,y coordinates of (0.19, 0.16) at 7 V. PMID- 26373117 TI - Crystallographic Wet Chemical Etching of Semipolar GaN (11-22) Grown on m-Plane Sapphire Substrates. AB - This paper reports the etch rates and etched surface morphology of semipolar GaN using a potassium hydroxide (KOH) solution. Semipolar (11-22) GaN could be etched easily using a KOH solution and the etch rate was higher than that of Ga-polar c plane GaN (0001). The etch rate was anisotropic and the highest etch rate was measured to be approximately 116 nm/min for the (1011) plane and 62 nm/min for the (11-20) plane GaN using a 4 M KOH solution at 100 degrees C, resulting in specific surface features, such as inclined trigonal cells. PMID- 26373118 TI - Kinetics for Steam and CO2 Reforming of Methane Over Ni/La/Al2O3 Catalyst. AB - Kinetic studies of mixed (steam and dry) reforming of methane on Ni/La/Al2O3 and Ni/La-Co (1, 3 wt%)/Al2O3 catalysts were performed in an atmospheric fixed-bed reactor. Kinetic parameters for the mixed reforming over these catalysts were obtained under reaction conditions free from heat and mass transfer limitations. Variables for the mixed reforming were the reaction temperature and partial pressure of reactants. The fitting of the experimental data for the rate of methane conversion, rCH4, using the power law rate equation rCH4 = k(PrCH4)alpha(PCO2)beta(PH2O)gamma showed that the reaction orders alpha, beta, and gamma are steady and obtained values equal to alpha = 1, beta = 0, and gamma = 0. In other words, among CH4, CO2, H2O, and H2, only CH4 reaction orders were not zero and they were affected by the promoters. The apparent activation energy on catalysts Ni/La/Al2O3, Ni/La-Co (1)/Al2O3 and Ni/La-Co (3)/Al2O3 is 85.2, 93.8, and 99.4 kJ/mol, respectively. The addition of Co to Ni/La/Al2O3 was increased the apparent activation energy of the mixed reforming reaction. And the Ni/La-Co (3 wt%)/Al2O3 catalyst showed the highest reforming activity and apparent activation energy. The Co promoters can increase the apparent activation energy of mixed reforming of methane. PMID- 26373119 TI - Effect of Bimetallic Ni-Cr Catalysts for Steam-CO2 Reforming of Methane at High Pressure. AB - The present work was to carry out the development of high performance Ni-based catalyst for Steam-CO2 reforming of methane (SCR) which is suitable for Fischer Tropsch synthesis of GTL- FPSO (floating, production, storage and offloading) process. The bimetallic Ni-Cr catalysts were prepared by co-impregnation method. The Ni and Cr loading amount were fixed at 12 wt% and 3~7 wt%, respectively. The catalytic reaction was conducted at 900 degrees C and 20 bar with reactant feed ratio of CH4:CO2:H2O:Ar = 1:0.8:1.3:1 and GHSV = 25,000 h(-1). The Cr-modified Ni/gamma-Al2O3 catalyst was characterized by BET surface area analysis, X-ray diffraction (XRD), H2-temperature programmed reduction (TPR), H2-chmisorption, CO2-temperature programmed desorption (TPD) and Transmission electron microscopy(TEM). To confirm the amount and type of the carbon deposition, the used catalysts were examined by Thermogravitic analysis (TGA) and Field emission scanning microscopy/Energy dispersive X-ray analysis (FE-SEM/EDX). It was found that the bimetallic Ni-Cr catalyst exhibits highly dispersed Ni particles with strong metal-to-support interaction (SMSI) as well as excellent catalytic activity, resulting in the suppression of Ni sintering and carbon deposition. PMID- 26373120 TI - Comparison of Strain in GaN-Based Blue Light-Emitting Diode Grown on Silicon(111) and Sapphire Substrates. AB - We compare the strain states and device performances of GaN-based blue light emitting diodes (LEDs) grown on Si(111) and sapphire substrates. The strain characteristics are investigated using micro-Raman spectroscopy and high resolution transmission electron microscopy. These analyses reveal that GaN layer grown on Si has a residual tensile strain in contrast to a compressive strain for GaN on sapphire, and quantum wells (QWs) on GaN/Si experience reduced lattice mismatch than those of GaN/sapphire. When external quantum efficiencies of LED on sapphire and Si substrates are compared, the LED on Si shows better efficiency droop characteristics and this is attributed to a decrease in piezo-electric field strength in InGaN/GaN layers owing to reduced lattice mismatch. PMID- 26373121 TI - Effect of Al2O3 Nano-Filler on Properties of Alkali/Alkaline-Earth Borosilicate Glass Composite Sealants. AB - The effect of adding Al2O3 nano-filler (5 and 10 vol%) to two different alkali/alkaline-earth borosilicate glass sealants, particularly on the viscosity and electrical characteristics of the glass composite sealants, was investigated to improve the cyclic sealing performance. The effects of the filler and base glass composition on the viscosities, electrical conductivities, and phase transformations of the sealants were investigated. The glass viscosity was decreased by replacing 20 mol% SrO with alkali and zirconium oxide in a base alkaline-earth glass. Alumina filler increased the high-temperature electrical conductivities, as well as the viscosities, of the heat-treated glass composite sealants. The replacement of 20 mol% SrO with alkali and zirconium oxide in the base alkaline-earth glass decreased the electrical conductivity of the heat treated glass containing Al2O3 nano-filler. PMID- 26373122 TI - Nanostructure Developments of TiO2 Nanocrystals and Aerogels and Their Dye Sensitized Solar Cell Application. AB - We synthesized TiO2 nanoparticles (TPs) as a reference via hydrothermal method and also TiO2 aerogels (TAs) via CO2 supercritical drying method. We investigated crystal phase transformation behavior of TPs and TAs with temperature. As prepared TPs are anatase and rutile phase transformation from anatase starts at 600 degrees C and was complete at 700 degrees C. However, TAs are amorphous phase until 300 degrees C and the crystallization to anatase occurs at 400 degrees C, and remains anantase phase until 700 degrees C. At the results of nitrogen adsorption and desorption analyses, TPs with specific surface area of 209 m2/g at 100 degrees C showed the decrease of the specific surface area and pore volume with increasing temperature and 95% of decrease at 700 degrees C. TAs showed higher specific surface area, 498 m2/g at 100 degrees C, and the decreasing trend according to temperature is similar with those of TPs. We prepared three types of photoelectrodes, TPs, TAs, and TATPs (1:1 TAs and TPs composite photoelectrode). After results of DSC photocurrent conversion efficiency measurements of the three type cells, we found that TATPs showed the improved cell efficiency by 1% point, compared with a reference TPs below 15 micrometer thickness. In conclusion, the introduction of nanoporous TAs can improve the photocurrent conversion efficiency due to their high specific surface area for high dye adsorption without degrading of electron transfer. PMID- 26373123 TI - Electrical Conduction Mechanism in Chemical Vapour Deposition Grown Multi-Wall Carbon Nanotubes Film. AB - Multi-walled carbon nanotubes are interesting systems where different aspects of conduction are observed, mostly due to their low dimensionalities and small dimensions. Electrical conduction mechanism in multi wall carbon nanotubes film is studied. The studied multi-walled nanotubes are grown by a low pressure chemical vapour deposition system. To understand the conduction mechanism in these nanotubes, temperature dependence of conductivity of the multi wall nanotubes film over a temperature range of (400-200 K) is studied. On the basis of the results, one may suggest the thermally activated conduction mechanism for the temperature range (400-300 K). The low temperature data is fitted with the hopping conduction for the transport of charge carriers in the temperature range of 300-200 K. This hopping conduction mechanism is characterized by variable range hopping (VRH), which shows complete agreement with the Mott's type of VRH mechanism. Applying this model, a number of Mott's parameters such as density of states, hopping distance, hopping energy are calculated. The calculated values of all the studied parameters matches well the reported results on other multi-wall nanotubes film. PMID- 26373124 TI - Molecular Packing of Metal-Organic Langmuir-Blodgett Films on Differently Passivated Si(001) Surfaces. AB - Langmuir-Blodgett films of standard amphiphilic molecules like cadmium arachidate (CdA) and nickel arachidate (NiA) are deposited on differently passivated (OH-, H and Br-passivated) Si(001) surfaces and molecular packing information from the top layer of all the films are obtained using atomic force microscopy (AFM). Molecular-resolution images, containing the information of molecular packing, are clearly obtained from the CdA films as the top surfaces are atomically flat, however, for the NiA films the information of the surface modulations are actually obtained due to the lack of top surface flatness. Triclinic packing of CdA molecules are obtained from the OH- and Br-terminated Si (OH-Si and Br-Si respectively), whereas herringbone packing are obtained from the H-terminated Si (H-Si). However, relatively loosely packing of NiA molecules causes molecular tilting which creates surface modulations and depending upon the substrate type the modulation covers nearly four (H-Si), six (Br-Si) and twelve (OH-Si) molecular area. PMID- 26373125 TI - Isomers of IC70BA and Their Photovoltaic Performance in Polymer Solar Cells. AB - Indene-C70 derivatives were synthesized, including indene-C70 mono-adduct (IC70MA), indene-C70 bis-adduct (IC70BA) and indene-C70 tris-adduct (IC70TA). All as-prepared fullerene adducts are in fact a mixture of isomers. The IC70BA mixture was further separated by high-performance liquid chromatography (HPLC) and two different IC70BA isomers were obtained. With the addition of the increased number of indene, the lowest unoccupied molecular orbital (LUMO) energy level of the C70 derivatives is also increased. IC70BA and its isomers have a slight difference in LUMO energy level, but show great differences in the absorption spectra. Polymer solar cells (PSCs) devices were fabricated under the same conditions with P3HT as donor, IC70BA and its isomer as acceptor, to examine the influence of the regioisomers on photovoltaic performance. The two IC70BA isomers exhibited varying power conversion efficiency (PCE) values of 2.80 and 3.18%, respectively, suggesting the molecular structure of the fullerene derivatives have an effect on polymer solar cells properties. PMID- 26373126 TI - Fabrication Characteristics of Silicon Nanowires via the Electrochemical Electroless Etching Method. AB - A silicon nanowire structure was fabricated using the electrochemical electroless etching method, involving electroless plating and the electrochemical etching process. The reflection of the absorption layer with the nanowires' structure was about 5%, which is better than a bulk-type solar cell (10%). PMID- 26373127 TI - Enhanced NO2 Gas Sensing Properties of WO3-Coated Multiwall Carbon Nanotube Sensors. AB - WO3-coated multiwall carbon nanotubes (MWCNTs) were fabricated by sputter deposition of WO3 on MWCNT paste. The outer diameters of WO3-coated MWCNTs ranged from 20 to 40 nm and the lengths ranged up to a few tens of micrometers. The low magnification TEM image of a typical WO3-coated CNT showed a CNT with an inner diameter of ~20 nm and a tube wall thickness of ~7 nm and WO3 shells with a thickness up to 10 nm at both edges of the tube. The WO3 shells were very nonuniform in thickness not only along the axis of the nanotube but also from one nanotube to the other. The sensing properties of multiple networked WO3-coated CNT sensors toward NO2 gas were examined. The WO3-coated MWCNT sensors showed responses of 120-221% over an NO2 concentration range of 1 to 5 ppm at room temperature. The responses were 1-2 fold higher than those of the pristine MWCNT sensor over the same NO2 concentration range. The origin of the enhancement of the MWCNTs in the response to NO2 by coating them with WO3 is discussed. PMID- 26373128 TI - Surface Plasmon Resonance-Enhanced Luminescence in Pd-Functionalized ZnO Nanowires. AB - Palladium (Pd)-functionalized ZnO nanowires were synthesized by thermal evaporation of a ZnO/graphite powder mixture followed by solution method. The ZnO nanowires had a rod-like morphology with relatively uniform width and length. The widths and lengths of the nanowires ranged from 30 to 100 nm and 5-10 um, respectively. The diameters of the Pd particles on the nanowires ranged from 5 to 50 nm. Effects of postannealing on the photoluminescence properties of Pd functionalized ZnO nanowires were examined. Thermal annealing resulted in an increase and decrease in the near-band edge (NBE) and deep level (DL) emission intensities of Pd-capped ZnO nanowires, respectively, whereas both the NBE and DL emission intensities of uncapped ZnO nanowires were increased by annealing. The intensity ratio of NBE emission to DL emission of the Pd-capped ZnO nanowires was increased ~18 fold by annealing in a hydrogen atmosphere. The underlying mechanism for NBE emission enhancement and DL emission suppression of Pd-capped ZnO nanorwires by postannealing is discussed based on the surface plasmon resonance effect of Pd. PMID- 26373129 TI - Local Structural Properties and Growth Mechanism of ZnO Nanorods on Hetero Interfaces. AB - We investigated the growth mechanism of ZnO(001) nanorods on SrTiO3(001) substrates. In the beginning of ZnO growth, a ZnO(110) film was developed on SrTiO3 substrates and then (001)-oriented ZnO nanorods grew on the ZnO(110) film. The strain energy of ZnO(110) growth on SrTiO3(001) planes was approximately 2.7 x 10(8) J/m3 whereas it was estimated to be ~1.61 x 10(9) J/m3 for ZnO(001) directly grown on SrTiO3(001) planes using Young's modulus of elasticity. Stress due to the lattice mismatch between ZnO and SrTiO3 was mostly relaxed in several monolayers and then ZnO(001) nanorods were finally formed along their easy growth directions. Keywords: ZnO Nanorod, Hetero-Interface, Local Structural, Growth Mechanism. PMID- 26373130 TI - Effect of Viscosities on the Surface Morphology and Crystallographic Properties of Hydroxyapatite Coated Titanium Dioxide Nanotubes. AB - Hydroxyapatite (HA) coating on biomaterials is crucial for bone growth. TiO2 naotubes having a larger specific area can also improve an osseointegration. In this study, anodized TiO2 nanotubes were coated with HA using sol-gel method with different viscosities of solution. Morphological characterization and crystal structures of the coated specimens were measured via field emission scanning electron microscope, transmission electron microscope, X-ray diffractometer, and fourier transforrm infrared spectroscopy. Nanosized hydroxyapatite particles were observed with sol viscosities at 1.95 cP and 0.94 cP inside the TiO2 nanotubes. When coated with the lower viscosity of solution, the TiO2 nanotubes were clearly observed. The crystallinity of HA increased as the temperature of heat treatment increased. The HA phase on the specimen was identified by PO4(3-) and OH-ion peaks in FT-IR spectra. PMID- 26373131 TI - Improvements of Pd/C Catalyst Support Characteristics by Various Physical Dispersion Methods. AB - Pd/C catalysts were prepared by ion exchange in aqueous solution. Physical dispersion methods including sonication, high share mixer and stirrer were used for though high dispersion of carbon. The physical properties of the prepared Pd/C particles were investigated by BET, XRD, and FE-TEM. The dispersion of Pd nanoparticles on carbon was measured on the basis of CO adsorption capacity using a pulse technique. FE-TEM micrographs showed that Pd nano particles possessed a spherical morphology with a narrow size distribution, with particles sizes ranging from 2-25 nm. The Pd particles prepared using sonication and high share mixer are well dispersed compared to the stirrer method. In addition, metal dispersions as calculated by CO uptake were 11.3, 20.4, and 25.0% for the stirrer, sonication and high share mixer methods, respectively. PMID- 26373132 TI - Electrical and Photocatalytic Property Change of Solution-Combusted ZnO Nanopowder by Heat-Treatment. AB - ZnO nanopowder was synthesized by a solution combustion method. This nanopowder was char- acterized by X-ray diffractometer (XRD), scanning electron microscope (SEM), four point probe, Hall measurement and photocatalytic reaction. The nanopowder was also investigated after heat-treating at 400 degrees C and 700 degrees C. The carrier concentrations were 8 x 10(20) cm(-3), 6 x 10(21) cm(-3) and 1.5 x 10(18) cm(-3) for the non heat-treated, the 400 degrees C heat-treated and the 700 degrees C heat-treated ZnO nanopowders respectively. Electrical resistivities of 1 Omega cm, 0.6 Omega cm and 2.6 Omega cm were obtained for the three kinds of heat-treated ZnO nanopowders respectively. These three kinds of nanopowders were then employed as photocatalysts to recover silver ions from wastewater. At 5 min of photocatalytic reaction time, the reaction removed 66.7%, 100% and 10.8% of the silver ions. The carrier concentration and photocatalytic efficiency of the 400 degrees C heat-treated one were 7.5 fold and 1.5 fold higher than those of the non heat-treated one respectively. However, the 700 degrees C heat-treated one showed far worse values than the non heat-treated one. This phenomenon was explained by carrier trap centers. PMID- 26373133 TI - Synthesis of Nanoporous Adsorbents Using Alum Sludge. AB - This study optimizes the synthesis process of pellet-type adsorbents using alum sludge. The effect of the binder and heat treatment temperature on the nanopore formation in the adsorbent is investigated. The pellet-type adsorbent prepared using the powder-type sludge from water treatment is determined to be a material that contains nanopores. The specific surface area is increased significantly after the calcination process in the range of 132-172 m2/g. With the calcination treatment, the breakthrough time in the formaldehyde adsorption increases remarkably with an optimum calcination temperature of 400 degrees C. The breakthrough capacity of the formaldehyde increases to a maximum 2.96 mg/g at this temperature. PMID- 26373134 TI - Synthesis and Characterisation of Silica-Modified Titania for Photocatalytic Decolouration of Crystal Violet. AB - In the past few years, silica-modified titania has drawn increasing attention due to their special properties making them ideal candidates for a wide range of applications. In this study, we report a novel method for the synthesis of silica modified titania by a sol-gel method using sodium silicate solution (1 M). The hydrolysis and condensation reactions of titanium dioxide (TiO2, Degussa Aeroxide(r) P25) in sodium silicate solution proceeded with citric acid (3 M) as a catalyst. The orbital shaking method was followed for the removal of sodium salt formed during the sol-gel process. Solvent exchange was carried out using methanol and hexane. Finally, chemical modification of the gel was conducted using trimethylchlorosilane followed by ambient pressure drying. The obtained silica-modified titania was characterised for nanostructural analysis using scanning electron microscopy and transmission electron microscopy. The nitrogen adsorption-desorption measurements were employed to investigate the BET surface area, pore structure and pore volume of specimens. Thermal gravimetric analysis showed exothermic peaks at temperature range of 90-190 degrees C representing the oxidation of organic groups from--Si-R network. The silica-modified titania showed high photocatalytic activity and an easy recovery using crystal violet as model water pollutant. PMID- 26373135 TI - Mechanochemical Synthesis and Rapid Consolidation of Nanostructured CoTi-Al2O3 Composite by Pulsed Current Activated Sintering and Its Mechanical Properties. AB - Nano-powders of CoTi and Al2O3 were synthesized from CoTiO3 and 2Al powders by high energy ball milling. Nanocrystalline Al2O3 reinforced composite was consolidated by pulsed current activated sintering within one minute from mechanochemically synthesized powders of CoTi and Al2O3. The relative density of the composite was 97%. The average hardness and fracture toughness values obtained were 1180 kg/mm2 and 8.5 MPa . m1/2, respectively. PMID- 26373136 TI - Ring Opening of Naphthenic Molecules Over Metal Containing Mesoporous Y Zeolite Catalyst. AB - Mesoporous Y zeolite (Meso-Y) with a uniform mesopore was synthesized via pseudomorphic syn- thesis. The Meso-Y supported Ni-W catalyst (NiW/Meso-Y) was introduced as a catalyst for the selective ring opening of naphthenic rings. The catalytic test for the ring opening of naphthalene as a model compound of multi ring aromatics was performed using a batch-type reaction system with both sulfided 20 wt% NiW/Meso-Y and NiW/Y catalysts under different reaction conditions. The catalytic results reveal that the Meso-Y supported NiW catalyst experiences a naphthalene conversion similar to the NiW/Y catalyst, but the NiW/Meso-Y catalyst has higher product yields for BTEX (benzene, toluene, ethyl benzene, and xylene) and the middle distillate than those of the NiW/Y catalyst at a low reaction temperature. These results suggest that the mesoporosity of the NiW/Meso-Y catalyst is more advantageous for the ring opening reaction of multi ring aromatics due to the easier access for the bulky molecules compared to the NiW/Y catalyst. PMID- 26373137 TI - A Study of Phosphorescent Light Emitting Using Cyclometalated Pt(II) Complexes. AB - The reaction of platinum [Pt(4-(N,N-bis(piridyl)amino)stilbene)]Cl2 with 5,5" (9,9-dioctyl-9H-fluorene- 2,7-diyl)di-2,2'-bipyridine, 2,2'-bipyridine, and 1,10 phenathroline affords the following complexes: [(4-(N,N bis(piridyl)amino)stilbene)Pt(5,5"-(9,9-dioctyl-9H-fluorene-2,7-diyl)di-2,2' bipyridine)] (1), [(4-(N,N-bis(piridyl)amino)stilbene)Pt(2,2'-bipyridine)] (2), and [(4-(N,N-bis(piridyl)amino)stilbene) Pt(1,10-phenathroline)] (3). In this study, new platinum complex compounds were synthesized utilizing the ligand of a 4-(N,N-bis(piridyl)amino)stilbene system. These complexes were analyzed using a 1H(13C)-NMR, UV-vis and PL spectrophotometer. The maximum wavelengths of complexes 1, 2, and 3 appear at 409 nm, 410 nm, and 503 nm, respectively. The quantum yields of these complexes are 0.32-0.92. PMID- 26373138 TI - Optimal Fabrication of P3HT:PCBM Based Organic Solar Cells with N-Type DMDCNQI Dopant. AB - We have fabricated P3HT and PCBM-based organic photovoltaic cells using DMDCNQI as a guest dopant material and an n-type buffer layer. We have investigated the physical effects of the DMD-CNQI molecule as a guest dopant and an n-type charge transfer buffer layer on the performance of the device by examining measurements of light current-voltage and photoluminescence characteristics. The device using DMDCNQI as a dopant and a buffer layer exhibited a remarkable increase in short circuit current density (Jsc) due to the ability of an electron acceptor and to the formation of a highly conducting charge transfer complex. In particular, the device consisting of ITO/PEDOT:PSS/P3HT:PCBM:DMDCNQI(1 wt%)/DMDCNQ/Al showed a maximum power conversion efficiency of 3.50%. PMID- 26373139 TI - Self-Assembly of CdTe Nanoparticles Into Nanowires by a Specific Wavelength of Light. AB - CdTe nanowires were synthesized from individual nanoparticles via self-assembly at a specific wavelength of light. The wavelength of 500 nm resulted in a self assembly of nanoparticles into nanowires. Most of the produced nanowires were straight and long in shape and their length ranged from 300 nm to 20 um. The oxidation of Te2- in CdTe nanoparticles under the visible light resulted in the assembly of nanowires consisting of several layers of individual nanoparticles. Transmission electron microscopy and scanning electron microscopy were performed to characterize the synthesized nanostructures. Energy-dispersive X-ray demonstrated the atomic percentage of nanowires. Photoluminescence showed that the wavelength of the nanostructures is slightly blue-shifted from 555 to 548 nm. PMID- 26373140 TI - Preparation of Aluminum Nanoparticles Using Bipolar Pulsed Electrical Discharge in Water. AB - Al nanoparticles were synthesized in liquid phase plasma using Al chloride as the precursor. CTAB was used as the surfactant to obtain well dispersed particles. When the surfactant was not added, large aggregated particles were generated. With increasing CTAB dosage, the size of the Al particles decreased and the degree of dispersion of the particles increased. At the initial stage of plasma discharge, dendrite shaped particles were produced. As discharge time evolved, however, particle size decreased and the particle morphology also changed into spherical shape. The solution pH decreased with increasing plasma discharge time. PMID- 26373141 TI - The Structure and Properties of Inductively Coupled Plasma Assisted Magnetron Sputtered Nanocrystalline CrN Coatings in Corrosion Protective Die Casting Molds. AB - Chromium nitride coatings for the surface modified die casting molds with various ICP powers have been prepared using ICP assisted magnetron sputtering. The applied ICP power was varied from 0 to 300 W. The deposited coatings were characterized post-deposition using X-ray diffractometry (XRD) and atomic force microscopy (AFM). Single CrN phased coatings with nano-grain sized (< 20 nm) were identified. The corrosion resistance and hardness of each coating were evaluated from potentiost at and nanoindentator. Superior corrosion protective coatings in excess of 20 GPa were deposited with assistance of ICP plasma during sputtering. PMID- 26373142 TI - Synthesis of Tricyclopentadiene Over Nanoporous MCM-41 Catalysts. AB - The objective of this study is to evaluate the catalytic potential of metal oxide/MCM-41 catalysts in dicyclopentadiene oligomerization/dicyclopentadiene oligomer isomerization. Molybdenum oxide, tungsten oxide, and titanium oxide were loaded on MCM-41 using the modified atomic layer deposition method. The amount of the acid site with weak strength has been increased through metal oxide deposition. The oligomer yield in dicyclopentadiene oligomerization/dicyclopentadiene oligomer isomerization did not change with increasing of the amount of acid site. The highest tricyclopentadiene isomer selectivity over the MoO3/MCM-41 catalyst could be attributed to having the highest overall number of acid sites among the catalysts. PMID- 26373143 TI - Microbially Induced Precipitation of Strontianite Nanoparticles. AB - The objectives of this study were to investigate the microbially mediated precipitation of strontium by microorganisms, and to examine the mineralogical characteristics of the precipitates. Wu Do-1 (Proteus mirabilis) enriched from rhodoliths was used to precipitate strontium at room temperature under aerobic environment. The growth of Wu Do-1 gradually increased over 16 days (OD600 = 2.6) and then decreased until 22 days (OD600 = 2.0) during microbial incubation for strontium precipitation. Also, the pH decreased from 6.5 to 5.3 over 4 days of incubation due to microbial oxidation of organic acids, and then the pH increased up to 8.6 at 25 days of incubation due to NH3+ generation. The Sr2+ concentration in the biotic group sharply decreased from 2,953 mg/L to 5.7 mg/L over 29 days of incubation. XRD, SEM-/TEM-EDS analyses revealed that the precipitates formed by Wu Do-1 (Proteus mirabilis) were identified as 20-70 nm sized strontianite (SrCO3). Therefore, these results suggested that formation of sparingly soluble Sr precipitates mediated by Wu Do-1 (Proteus mirabilis) sequesters strontium and carbon dioxide into a more stable and less toxic form such as strontianite (SrCO3). These results also suggest that bioremediation of metal-contaminated water and biominealization of carbonate minerals may be feasible in the marine environment. PMID- 26373144 TI - Ac2O/HCl Modulated Fluorescence On-Off Model Based on Arylmaleimide. AB - A dye incorporated naphthalene and bisindolylmaleimide was synthesized. The hydroxyl attached to naphthalene lead to fluorescence quench of binindolylmaleimide. The fluorescence was recovered upon acetic anhydride addition. However, HCl addition quenched the fluorescence emission again. Therefore, a switchable emission "off-on" model can be established. Frontier molecular orbital analysis uncovered the underlying signal mechanism. PMID- 26373145 TI - Spectral Switching of Naphthalimide-Coumarin Induced by F-. AB - A highly selective color sensor based on naphthalimide and coumarin was reported. Upon addition of F-, the solution color changed from pale yellow to deep blue. The sensor shows excellent selectivity against other common anions. The underlying mechanism for the color change is based on the deprotonation/protonation of the dye. Frontier molecular orbitals analysis gives further insight about the signaling mechanism. PMID- 26373146 TI - Effect of Nanoscale Ag Film Thickness on the Electrical and Optical Properties of Transparent IZTO/Ag/IZTO Multilayer Films Deposited on Glass Substrates. AB - The effect of nanoscale Ag film thickness on the electrical and optical properties in transparent conducting oxide films consisting of an IZTO/Ag/IZTO multilayer were investigated. The homoge- neous morphologies of the Ag films sandwiched between the IZTO films affected the optical and electrical properties of the IZTO/Ag/IZTO multilayer films. The transmittance and resistivity of the IZTO/Ag/IZTO multilayer films decreased with increasing Ag film thickness. The resistivities of the IZTO/Ag/IZTO multilayer films grown on glass substrates were decreased by using an Ag thin inter- layer in comparison with that of the IZTO single layer. PMID- 26373147 TI - Size-Tunable Fe3O4 Spherical Nanoclusters Through a One-Pot Hydrothermal Synthesis. AB - A new method is presented for the synthesis of monodisperse, size-tunable Fe3O4 spherical nanocluster particles through a simple, one-step hydrothermal reaction, according to a kinetics-controlled self-assembly process of smaller nanocrystals into hierarchical mesoporous aggregates. The mean diameter of the particles can be controlled over a broad range up to ~230 nm by simply varying the concentration of the precipitating reagent (urea or ammonia). The particles can be easily dispersed in water with excellent colloidal stability, exhibit a high surface area of ~ 60 m2 g(-1), and demonstrate size-dependent magnetic separation kinetics, where the larger nanoclusters exhibit rapid magnetophoresis, and the smaller nanoclusters remain inseparable. Thus particle size control is essential for improving magnetic separation processes. PMID- 26373148 TI - Assembly of Maghemite Nanoparticles Into Particulate Nanosheets and Their Application in Wastewater Treatment. AB - The maghemite particulate nanosheets (MPNs) are prepared in solvothermal system by connecting the nanoparticles in two-dimension. The interconnected MPNs sustain a mesopores structure with a high accessible surface area of 164 m2/g, and have a high performance for Cr6+ adsorption. The Cr6+ removal process fit with Langmuir adsorption model with an adsorption capacity of 20.41 mg/g. The purified solution could reach a residual concentration of 0.002 mg/L for MPNs, which is much less than the concentration in the solution of 0.249 mg/L when the nanoparticles are used. The synthesized MPNs with a saturation magnetization of 70.51 emu/g at room temperature can be easily collected and separated by an external magnet in liquid. Exchange coupling and shape anisotropy are the main reason for the higher Ms of MPNs. The unique structure with large surface area and high saturation magnetization make the MPNs favourable for the application of magnetic separation. PMID- 26373149 TI - Vapor Phase Dehydration of Glycerol to Acrolein Over SBA-15 Supported Vanadium Substituted Phosphomolybdic Acid Catalyst. AB - Vapor phase dehydration of glycerol to acrolein was investigated over heteropolyacid (HPA) catalysts containing vanadium substituted phosphomolybdic acid (H4PMo11VO40) supported on mesoporous SBA-15. A series of HPA catalysts with HPA loadings varying from 10-50 wt% were prepared by impregnation method on SBA 15 support. The catalysts were characterized by X-ray diffraction, Raman spectroscopy, Fourier Transform infrared spectroscopy, temperature-programmed desorption of NH3, pyridine adsorbed FT-IR spectroscopy, scanning electron microscopy, pore size distribution and specific surface area measurements. The nature of acidic sites was examined by pyridine adsorbed FT-IR spectroscopy. XRD results suggest that the active phase containing HPA was highly dispersed at lower loadings on the support. FT-IR and Raman spectra results confirm that the presence of primary Keggin ion structure of HPA on the support and it was not affected during the preparation of catalysts. Pore size distribution results reveal that all the samples show unimodel pore size distribution with well depicted mesoporous structure. NH3-TPD results suggest that the acidity of catalysts increased with increase of HPA loading. The findings of acidity measurements by FT-IR spectra of pyridine adsorption reveals that the catalysts consist both the Bronsted and Lewis acidic sites and the amount of Bronsted acidic sites are increasing with HPA loading. SBA-15 supported vanadium substituted phosphomolybdic acid catalysts are found to be highly active during the dehydration reaction and exhibited 100% conversion of glycerol (10 wt% of glycerol) and the acrolein selectivity was appreciably changed with HPA active phase loading. The catalytic functionalities during glycerol dehydration are well correlated with surface acidity of the catalysts. PMID- 26373150 TI - Vapor Phase Hydrogenation of Nitrobenzene to Aniline Over Carbon Supported Ruthenium Catalysts. AB - A series of Ru/Carbon catalysts (0.5-6.0 wt%) were prepared by impregnation method. The catalysts were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), temperature programmed reduction (TPR), X-ray photoelectron spectroscopy (XPS), CO-chemisorption, surface area and pore-size distribution measurements. The catalytic activities were evaluated for the vapor phase hydrogenation of nitrobenzene. The dispersion measured by CO-uptake values suggests that a decrease of dispersion is observed with increasing Ru loading on carbon support. These findings are well supported by the crystallite size measured from XRD measurements. XPS study reveals the formation of Ru0 after reduction at 573 K for 3 h. The catalysts exhibit high conversion/selectivity at 4.5 wt% Ru loading during hydrogenation reaction. The particle size measured from CO-chemisorption and TEM analysis are related to the TOF during the hydrogenation reaction. Ru/C catalysts are found to show higher conversion/selectivities during hydrogenation of nitrobenzene to aniline. PMID- 26373151 TI - Synthesis of Copper-Based Nanostructured Catalysts on SiO2-Al2O3, SiO2-TiO2, and SiO2-ZrO2 Supports for NO Reduction. AB - The selective catalytic reduction of NO over a series of Cu-based catalysts supported on modified silica including SiO2-Al2O3, SiO2-TiO2, and SiO2-ZrO2 prepared via a sol-gel process and a flame spray pyrolysis (FSP) was studied. The prepared catalysts were characterized by means of TEM, XRD, XRF, TPR, and nitrogen physisorption measurement techniques, to determine particle diameter, morphology, crystallinity, phase composition, copper reducibility, surface area, and pore size of catalysts. The particles obtained from sol-gel method were almost spherical while the particles obtained from the FSP were clearly spherical and non-porous nanosized particles. The effects of Si:Al, Si:Ti, and Si:Zr molar ratio of precursor were identified as the domain for different crystalline phase of materials. It was clearly seen that a high SiO2 content inhibited the crystallization of materials. The BET surface area of catalysts obtained from sol gel method was higher than that from the FSP and it shows that surface area increased with increasing SiO2 molar ratio due to high surface area from SiO2. The catalyst performances were tested for the selective catalytic reduction of NO with H2. It was found that the catalyst prepared over 7 wt% Cu on Si02-Al2O3 support was the most active compared with the others which converted NO as more than 70%. Moreover, the excess copper decreased the performance of NO reduction, due to the formation of CuO agglomeration covered on the porous silica as well as the alumina surface, preventing the direct contact of CO2 and AL2O3. PMID- 26373152 TI - Photocatalytic Degradation of Di-n-Butyl Phthalate by N-Doped Ti/13X/MCM-41 Molecular Sieve. AB - Di-n-butyl phthalate (DBP) is a type of phthalate ester, and has been classified as an environmental endocrine disruptor. It causes serious harm to the environment and humans and it is found widely in air, waste water, rivers and soil. In recent years, an increasing number of studies examined the removal of DBP. Photocatalytic degradation has been of particular interest because of its efficient and thorough advantages and is the focus of this study. Here we use a composite material of N-Ti/13X/MCM-41, synthesized, using 13X and tetraethyl orthosilicate as raw material, CTAB as structural template, tetrabutyl titanate and urea under hydrothermal conditions. The optimized experimental conditions, such as, Si/Al (molar ratio), pH value, crystallization time, calcination temperature and N/Ti (molar ratio), were tested using photodegradation experiments of DBP. The samples were characterized by XRD, TEM, FT-IR, N2 adsorption-desorption. Experimental results reveal the surface area of the N Ti/13X/MCM-41 to be 664 m2 g(-1) and the average pore sizes to be 2.79 nm. TEM micrographs showed the N-Ti/13X/MCM-41 consists of aggregates of spherical particles, similar to the shapes associated with standard MCM-41 synthesized under basic conditions. Photocatalytic degradation experimental results revealed that optimal synthesis of the composite material occurs when Si/Al = 15, pH = 9.0, crystallization time is 48 hours, calcination temperature is 350 degrees C and the N/Ti ratios is 2.0. Under such conditions, the degradation efficiency of DBP more was found to be more than 90%. PMID- 26373153 TI - Biomarker Evaluation in Fish After Prolonged Exposure to Nano-TiO2: Influence of Illumination Conditions and Crystal Phase. AB - In this study, we evaluated the effects of prolonged exposure to two different nano-TiO2 crystal phases under different illumination conditions. Fish (Piaractus mesopotamicus) were exposed for 21 days to 100 mg/L of nano-TiO2 anatase and a mixture of anatase:rutile (80%:20%) under visible light and UV light (UVA and B, 22.47 J/cm2/h). The following oxidative stress biomarkers were mon- itored: concentrations of lipid hydroperoxide (LPO), carbonylated proteins (PCO), and specific activ- ities of superoxide dismutase (SOD), catalase (CAT) and glutathione S-transferase (GST). Other biomarkers as well as specific activities of acid phosphatase (AP), Na+, K(+)-ATPase and metalloth- ionein levels (MT) were also evaluated. Moreover, micronucleus and comet assays were performed to assess genotoxicity. Our results showed low toxicity of nano-TiO2 to fish and lack of titanium accumulation in muscle tissue. However, it was observed the occurrence of sublethal effects that were influenced by nano-TiO2 crystal phase and illumination condition. Pure anatase caused more oxidative damage without co exposure to UV, while the mixture anatase:rutile caused more sub- lethal effects when exposure occurred under UV. These findings show that the specific activity of CAT, GST, PCO levels and comet assay are useful as biomarkers of prolonged exposure to nano- TiO2. Overall, our study substantiates the development and implementation of nanoecotoxicological protocols. PMID- 26373154 TI - Photoluminescence Properties of SrMoO4:Eu3+, Sm3+ Nanophosphors Prepared by Sol Gel Method. AB - Novel red light-emitting nanophosphors of SrMoO4:Eu3+, Sm3+ were synthesized by a facile sol-gel method. Particles have sizes in the range of 50-80 nm. The structures, morphologies and optical properties of as-prepared products were characterized by means of X-ray diffraction (XRD), transmission electron microscope (TEM) and photo luminescent (PL). The results indicate that the red emission intensity was enhanced significantly with the increase of Sm3+ doping concentrations. When the mole fraction of Sm3+ is 2%, the emission intensity of red light is the strongest. It has been found that the incorporation of R+(Li+, Na+) into SrMoO4:Eu3+, Sm3+ phosphor could lead to a remarkable increase of photoluminescence. Thus, it is considered to be efficient red-emitting phosphors. PMID- 26373155 TI - Synthesis and Luminescent Property of Poly(9-(3-vinyl-phenyl)-anthracene). AB - Polymer light-emitting diodes (PLEDs) have attracted much attention from academia and industry field because of their various applications such as large area flat panel displays and lightings. In this paper, we suggest new blue emitting polymer based on anthracene, Poly(9-(3-Vinyl-phenyl)-anthracene) (PVPA). From NMR data, vinyl group protons were disappeared and aromatic protons showed broad proton peaks because of polymer characteristics. PVPA had film property well and it exhibited vivid PL maximum values of 431, 455, 482 nm and broad PL spectrum. Three dopants for green, red, yellow were used to PVPA, all energy transfer was happened well. By using rubrene dopant of yellow emission, doped film provided white PL. PMID- 26373156 TI - Highly Efficient White Organic Light Emitting Diodes Using New Blue Fluorescence Emitter. AB - Two different emitting compounds, 1-[1,1';3',1"]Terphenyl-5'-yl-6-(10 [1,1';3',1"]terpheny-5'-yl- anthracen-9-yl)-pyrene (TP-AP-TP) and Poly-phenylene vinylene derivative (PDY 132) were used to white OLED device. By incorporating adjacent blue and yellow emitting layers in a multi-layered structure, highly efficient white emission has been attained. The device was fabricated with a hybrid configuration structure: ITO/PEDOT (40 nm)/PDY-132 (8-50 nm)/ NPB (10 nm)/TP-AP-TP (30 nm)/Alq3 (20 nm)/LiF (1 nm)/Al (200 nm). After fixing TP-AP-TP thickness of 30 nm by evaporation, PDY-132 thickness varied with 8, 15, 35, and 50 nm by spin coating in device. The luminance efficiency of the white devices at 10 mA/cm2 were 2.93 cd/A-6.55 cd/A. One of white devices showed 6.55 cd/A and white color of (0.290, 0.331). PMID- 26373157 TI - Synthesis and Characteristics of Fullerene Derivatives with Hexyl Perylene Moieties as N-Type Materials in Organic Solar Cells. AB - Recently, fullerene derivatives have received significant attention due to their potential impacts on the development of high performance organic photovoltaic (OPV) cells. One of the most successful fullerene derivatives thus far is [6, 6] phenyl-C61-butyric acid methyl ester (PCBM), which is being used as an electron acceptor material. However, PCBM has some disadvantages concerning its application in OPV cells, such as a weak absorption rate in the visible region and a relatively low LUMO level. In the present work, we synthesized a novel fullerene derivative, called hexyl perylene fullerene (HPF), which contains a hexyl perylene moiety. The HPF molecules showed two absorption peaks at 340 nm and 450 nm corresponding to the fullerene and to the perylene moiety, respectively. 1,8-octanedithiol was used as an additive to improve the compatibility between the poly(3-hexylthiophene) (P3HT) and the synthesized HPF The characteristics of an OPV cell composed of ITO/PEDOT:PSS/P3HT:HPF:1,8 octanedithiol/Al were investigated. PMID- 26373158 TI - Photocatalytic Decomposition of Methylene Blue Over MIL-53(Fe) Prepared Using Microwave-Assisted Process Under Visible Light Irradiation. AB - Iron-based MIL-53 crystals with uniform size were successfully synthesized using a microwave-assisted solvothermal method and characterized by XRD, FE-SEM and DRS. We also investigated the photocatalytic activity of MIL-53(Fe) for the decomposition of methylene blue using H2O2 as an electron acceptor. From XRD and SEM results, the fully crystallized MIL-53(Fe) materials were obtained regardless of preparation method. From DRS results, MIL-53(Fe) samples prepared using microwave-assisted process displayed the absorption spectrum up to the visible region and then they showed the high photocatalytic activity under visible light irradiation. The MIL-53(Fe) catalyst prepared by two times microwave irradiation showed the highest activity. PMID- 26373159 TI - Impact of Nano-Pore Structure in Harden Non-Sintering Cement. AB - This study investigates the nano pore structure of non-sintering cement (NSC) matrix. The result of pore structure properties showed no considerable difference in the total pore volume, but presented a large distinction in distribution of pore diameter by cement mixing ratio. The pore-diameter of NSC paste shows that occupation ratio of pore diameter below 10 nm was larger and was smaller than ordinary Portland cement (OPC) and blast-furnace slag cement (BSC) at pore diameter of over 10 nm. The reasons are due to the hydrate such as C-S-H gel and ettringite which formed dense nano pore structure of NSC matrix. PMID- 26373160 TI - Preparations of Platinum Nanoparticles and Their Catalytic Performances. AB - This work investigates the effect of reducing agents and stabilizing agent on the preparation of platinum nanoparticles. We used H2PtCl6 as a precursor and hydrogen and sodium borohydride as reducing agents to prepare colloidal platinum nanoparticles. Polyvinylpyrrolidones (PVPs) is used as a stabilizing agent. Hydrogen and sodium borohydride are used as reducing agents. The prepared platinum nanoparticles are characterized by transmission electron microscopy (TEM) and X-ray diffractometer (XRD). The concentrations of the precursor and the stabilizing agent influence the size of platinum nanoparticles, while the reducing agents influence the morphologies and structures of platinum nanoparticles. Supported platinum catalysts (CPt-NaBH4, CPt-H2) are prepared from colloidal platinum nanoparticles and gamma-Al2O3. For comparison, another supported platinum catalyst (IPt) is prepared by the conventional impregnation method with an aqueous H2PtCL6 solution and gamma-AL2O3. The catalytic activities of CPts are superior to that of IPt on the basis of benzene conversion. PMID- 26373161 TI - Preparation of Nanosized TiO2 Powder from Spent Titanium Chip by Sol-Gel Method. AB - The TiO2 powder was prepared from the spent titanium chips by applying the sol gel method with neutralization by NaOH solution. The prepared TiO2 powder was characterized using a particle size analysis, BET surface area, and XRD analysis. The crystal structure of the TiO2 powder was rutile type, and the powder was obtained to be nanosized. BET surface area of TiO2 powder was 118 m2/g, average particle size was 266.5 nm. The photocatalytic property of the TiO2 powder was evaluated as decomposition rate of methylene blue (MB) by using a liquid phase stirred reactor. Decomposition rate on TiO2 powder (P-25) was 1.5 times higher than that of the prepared TiO2 powder. Decomposition rate on the prepared TiO2 powder was linearly increased with increasing the amount of TiO2 powder, and approached to a specific value. MB concentration and decomposition rate was not correlated within the experimental range. The maximum value of decomposition rate at about pH 8 was 62%. PMID- 26373162 TI - High Frequency Induction Heated Synthesis and Consolidation of Nanostructured TaSi2-WSi2 Composite. AB - A dense nanostructured TaSi2-WSi2 composite was simultaneously synthesized and sintered by the high frequency induction heating method within 2 minutes from mechanically activated powder of Ta, W and Si. A highly-dense TaSi2-WSi2 composite was produced under simultaneous application of a 80 MPa pressure and the induced current. The mechanical properties and microstructure were investigated. PMID- 26373163 TI - Nano Copper Powders Synthesized by a Polymer Solution Method at Low Temperature. AB - Copper (Cu) nano particles were successfully fabricated at a significantly low temperature through a simple polymer solution route. In the process, the organic inorganic precursor sols were turned to porous gels exhibiting volume expansion during the drying process. The PVA polymer, as an organic carrier, contributed to make an atom-scale homogeneous copper precursor gel, which resulted in fully crystallized, nano-sized copper powders through a low calcination temperature of 300 degrees C under Ar-4%H2 atmosphere. Variations in the processing technique, such as the content of PVA and calcination temperature, affected the microstructure and crystallization behavior of the synthesized powders. The copper powder synthesized with the PVA content of 4:1 ratio showed a crystallite size of about 10 nm or less with a high surface area. In this paper, the PVA solution technique for the fabrication of a nano-sized copper powder is introduced. The effects of the PVA content and calcination conditions on the powder morphology and crystallization are also studied. The characterization of the synthesized powders is conducted by using XRD, DTA/TG, SEM and TEM. PMID- 26373164 TI - Fabrication of Hierarchical Metallic Nanocomposite Core/Metal Shell Nanostructures by Self-Assembly. AB - Direct self-assembly of metals with inorganic nanoparticles into hierarchical nanostructures is highly demanded. Here we developed a simple methodology for direct self-assembly of metals (pure or alloy) and nanoparticles into hierarchical metallic nanocomposites core/metal shell nanostructures in immiscible molten salt, driven by the minimization of interfacial energy of the system. The core metals and nanoparticles firstly assemble into metal nanoparticle nanocomposite microspheres. The formed nanocomposite microspheres could be utilized as new building blocks for a subsequent self-assembly procedure to be coated form a metal shell. This work provide a novel and simple method to fabricate hierarchical nanocomposites core/metal shell nanostructures for numerous applications. PMID- 26373165 TI - Structure and Conductance of Aluminum Nanocontacts Studied by In Situ High Resolution Transmission Electron Microscopy. AB - The structural dynamics and conductance of aluminum nanocontacts (NCs) during mechanical breaking was investigated in situ by high-resolution transmission electron microscopy. When the minimum cross-sectional width of the NCs was found to decrease to less than 1.3 nm at a bias voltage of 12.9 mV, a large strain was introduced in the minimum cross section region. The critical width of straining increased with bias voltage. Below the critical width, the current density started to decrease. PMID- 26373166 TI - Acyldepsipeptide antibiotics--current state of knowledge. AB - The objective of this paper is to review and summarize the antimicrobial efficacy of the acyldepsipeptides and to indicate the prospects of the therapeutic values of these compounds. This work is enriched by the description of the mutations within the clpP1clpP2 and c1pP3clpP4 operons of Streptomyces lividans, which are considered to be the potential mechanism of the acyldepsipeptide (ADEP) resistance development. The researchers' conclusions demonstrated a significant impact on microorganisms including the destabilization of bacterial cell division in Bacillus subtilis 168, Staphylococcus aureus HG001 and Streptococcus pneumoniae G9A strains. The results of animal studies show higher bactericidal effectiveness of the acyldepsipeptides ADEP-2 and ADEP-4 compared to linezolid. ADEPs may be considered as a very important mechanism of defense against the increasing resistance of microorganisms . They also might prevent or reduce the risk of many epidemiological events. PMID- 26373167 TI - Intestinal Microbiota, Obesity and Prebiotics. AB - Over the past few decades there has been a significant increase in the prevalence of obesity in both children and adults. Obesity is a disease that has reached epidemic levels on a global scale. The development of obesity is associated with both environmental and genetic factors. Recent studies indicate that intestinal microorganisms play an important function in maintaining normal body weight. One of the objectives in the gut microbiota research is to determine the role it plays and can it be a reliable biomarker of disease risk, including the predisposition to obesity. This article discusses (1) the role of prebiotics and gut microbiota in maintaining a healthy body weight and (2) potential influence on the gut microbiota in the prevention and treatment of obesity. PMID- 26373168 TI - Characteristics of the Pseudomonas aeruginosa PA01 Intercellular Signaling Pathway (Quorum Sensing) Functioning in Presence of Porphyrins Bismuth Complexes. AB - The influence of synthetic and natural porphyrins bismuth complexes on P. aeruginosa quorum sensing system was carried out by detection of the pyocyanin, rhamnolipids and autoinducers biosynthesis level. The highest ability to reduce pyocyanin biosynthesis showed Bi(III)-TPP. Rhamnolipids production level also decreased in the presence of studied compounds. This effect was the most expressed in presence of 40 and 80 uM of the synthetic meso-substituted porphyrins. Autoinducers biosynthesis, especially 3-oxo-C12-HSL was suppressed in presence of the bismuth complexes. That suggest that the mechanisms of action of this substances is an inhibition of signaling molecules or/and receptor for them. PMID- 26373169 TI - Kinetic Properties of Pyruvate Ferredoxin Oxidoreductase of Intestinal Sulfate Reducing Bacteria Desulfovibrio piger Vib-7 and Desulfomicrobium sp. Rod-9. AB - Intestinal sulfate-reducing bacteria reduce sulfate ions to hydrogen sulfide causing inflammatory bowel diseases of humans and animals. The bacteria consume lactate as electron donor which is oxidized to acetate via pyruvate in process of the dissimilatory sulfate reduction. Pyruvate-ferredoxin oxidoreductase activity and the kinetic properties of the enzyme from intestinal sulfate-reducing bacteria Desulfovibrio piger and Desulfomicrobium sp. have never been well characterized and have not been yet studied. In this paper we present for the first time the specific activity of pyruvate-ferredoxin oxidoreductase and the kinetic properties of the enzyme in cell-free extracts of both D. piger Vib-7 and Desulfomicrobium sp. Rod-9 intestinal bacterial strains. Microbiological, biochemical, biophysical and statistical methods were used in this work. The optimal temperature (+35 degrees C) and pH 8.5 for enzyme reaction were determined. The spectral analysis of the puri- fied pyruvate-ferredoxin oxidoreductase from the cell-free extracts was demonstrated. Analysis of the kinetic properties of the studied enzyme was carried out. Initial (instantaneous) reaction velocity (V0), maximum amount of the product of reaction (Pmax), the reaction time (half saturation period) and maximum velocity of the pyruvate ferredoxin oxidoreductase reaction (V ) were defined. Michaelis constants (Km) of the enzyme reaction were calculated for both intestinal bacterial strains. The studies of the kinetic enzyme properties in the intestinal sulfate-reducing bacteria strains in detail can be prospects for clarifying the etiological role of these bacteria in the development of inflammatory bowel diseases. PMID- 26373170 TI - The Application of Impedance Microsensors for Real-Time Analysis of Pseudomonas aeruginosa Biofilm Formation. AB - Biofilms formed by nosocomial pathogens represent a major threat to patients undergoing invasive procedures. As prophylaxis remains the most efficient anti biofilm option, it is of paramount importance to develop diagnostic tools able to detect biofilm at the early stage of formation. The present study investigates the ability of impedance microsensors to detect Pseudomonas aeruginosa biofilm presence using the impedance spectroscopy method. The measured data were analyzed using Electrical Equivalent Circuit modelling (EEC). It allowed to recognize conduction and polarization phenomena on the sensors surface and in its environment. The impedance assay results, confirmed by means of electron microscopy and quantitative cultures, indicate that specific EEC parameters may be used for monitoring the development of pseudomonal biofilm. PMID- 26373171 TI - Chemical Composition and Antibacterial Activity of Essential Oils of Two Species of Lamiaceae against Phytopathogenic Bacteria. AB - In this study, we aimed to determine chemical composition and antibacterial activities of Satureja hortensis and Calamintha nepeta against to 20 phytopathogenic bacteria causing serious crop loss. The essential oils of S. hortensis and C. nepeta were isolated by the hydrodistillation method and the chemical composition of the essential oils were analyzed by GC-MS. The antibacterial properties of the essential oils were evaluated against 20 phytopathogenic bacteria through Disc diffusion assay and micro dilution assay. The results revealed that the essential oils of S. hortensis and C. nepeta have significant antibacterial activity. Furthermore, the findings of the study are valuable for future investigations focusing on the alternative natural compounds to control plant diseases. PMID- 26373172 TI - Investigation of the Actual Causes of Hip Joint Implant Loosening Classified as Aseptic--Analysis of Microbiological Culture Results and Levels of Inflammatory Markers. AB - Loosening of the hip joint prosthesis is considered as one of the most significant postoperative complications in recent years. The laboratory diagnostic procedure used to differentiate periprosthetic infection from aseptic loosening is very difficult because of the biofilm which microorganisms form on the implant surface. The purpose of this research was to evaluate the level of concordance between clinical classification of implant loosening among 50 patients subjected to reimplantation procedure and laboratory investigation of PJI including microbiological culture results and the levels of inflammatory markers assessed in the patients' synovial fluid samples, serum, and full blood. The synovial fluid was collected for leukocyte count, differential cell count, and culture on standard media. The levels of systemic inflammation markers such as the ESR and CRP concentration were determined in serum and full blood. Tissue samples were collected for microbiological studies. Components from endoprostheses were exposed to ultrasound in a process called sonication. Among the parameters measured in serum and full blood the levels of ESR and CRP were higher in the septic group of patients. Cytologic analysis of synovial fluid was in correlation with microbiologic identification. The most frequent isolated bacteria was Staphylococcus epidermidis. Culture results from materials such as synovial fluid, sonicate and tissues are crucial to establish the infectious aetiology of the loosening. Microscopic analysis of synovial fluid represents a simple, rapid and accurate method for differentiating PJI from aseptic failure. Sonication increases detection of the infectious process, and culture results are in correlation with the cytologic analysis of synovial fluid. PMID- 26373173 TI - In Vitro Studies of Antibacterial and Antifungal Wound Dressings Comprising H2TiO3 and SiO2 Nanoparticles. AB - The incidence rate of the infected and complex wound is established at approximately 40,000/1 million of the world's adult population. The aim of this study was to assess the efficiency of three novel types of wound dressings comprising sodium chloride, metatitanic acid and silicon dioxide nanoparticles. The study design was to prove their antimicrobial properties against the microorganisms most commonly causing wound infections. The study evaluated the antimicrobial effect of tested dressings on referenced strains of bacteria (ATCC collection, Argenta, Poland) and strains of fungi species (our own collection of fungi cultured from patients). The dressings were tested with both bacterial and fungal strains on solid media (Mueller-Hinton, Sobouraud, bioMerieux, France) in the standard method. The results confirmed the inhibition of growth of bacteria and revealed zones of inhibition for Escherichia coli, Staphylococcus aureus and Enterococcus faecalis. Significant zones of inhibition were established for Staphylococcus aureus and for fungi species of the Candida sp. These results would be crucial due to the fact of the low availability of antifungal therapeutics for both systemic and topical usage. Moreover, the current standard of antifungal treatment is associated with high costs and high toxicity in general. The preliminary results are very promising but further studies are necessary. Based on the obtained results, the tested dressings may contribute to the development of the surgical armamentarium of complex wound management in the near future. PMID- 26373174 TI - Escherichia coli and Salmonella spp. Early Diagnosis and Seasonal Monitoring in the Sewage Treatment Process by EMA-qPCR Method. AB - Numerous studies have recently shown that molecular biology tools can allow for early diagnosis of pathogens and can substitute existing cost and time-taking traditional methods. One of them, the qPCR, is successfully used in microbiology and its utility has been assessed for many different biological materials. The aim of this study was to: 1) determine, optimize and apply qPCR as a method to detect Escherichia coli and Salmonella spp. in primary influents and final effluents from municipal wastewater treatment plant 2) define if addition of ethidium bromide monoazide (EMA) before DNA extraction can allow to distinguish between alive and dead bacteria, 3) quantify E. coli and Salmonella spp. in wastewater during four seasons by qPCR and traditional spread plate method and determine the correlation between the indicator and pathogenic microorganisms. The obtained results has shown that qPCR can be used as a quantitative method in the diagnosis of investigated bacteria in wastewater with EMA pretreatment as a crucial step for a proper quantitative analysis of the presence of these bacteria in wastewater. Both E. coli and Salmonella spp. bacteria species were present in all samples of primary influents and final effluents. Our study shown that the quantity of investigated bacteria is strictly correlated with the season that they were obtained in. PMID- 26373175 TI - Biologically-Induced Precipitation of Minerals in a Medium with Zinc Under Sulfate-Reducing Conditions. AB - Sulfate-reducing microbial communities were enriched from soils collected in areas with crude-oil exploitation. Cultures were grown in modified Postgate C medium and minimal medium, with ethanol or lactate as an electron donor. The batch cultures were grown with addition of zinc in concentrations of 100-700 mg/l. A lack of increased protein concentration in the solutions compared with the control batch, was noted in cultures containing over 200 mg Zn2+/l. The 16S rRNA method was applied to determine the specific composition of the selected microorganism communities. The analysis indicated the presence of Desulfovibrio spp., Desulfobulbus spp. and Desulfotomaculum spp. in the communities. Diffractometric analysis indicated the presence of biogenic sphalerite in cultures with 100 and 200 mg Zn2+/l and elemental sulfur in cultures with 200 mg Zn2+/l. Other post culture sediments (300-700 mg Zn2+/l) contained only hopeite [Zn3(PO4)2.4H2O] formed abiotically during the experiment, which was confirmed by studies of the activity of sulfate-reducing microbial communities. PMID- 26373176 TI - Role of Antagonistic Microorganisms and Organic Amendment in Stimulating the Defense System of Okra Against Root Rotting Fungi. AB - Without application of chemical pesticides control of soilborne diseases is a great challenge. Stimulation of natural plant's defense is considered as one of the most promising alternative strategy for crop protection. Organic amendment of soil besides direct suppressing the pathogen, has been reported to have an influence on phytochemicals in plants. In the present study, Pseudomonas aeruginosa, a plant growth promoting rhizobacterium and Paecilomyces lilacinus, an egg parasite of root knot and cysts nematodes were examined individually and in combination in soil amended with cotton cake for suppressing the root rotting fungi and stimulating the synthesis of polyphenols and improving the antioxidant status in okra. Application of P. aeruginosa and P. lilacinus in soil amended with cotton cake significantly (P < 0.05) suppressed Macrophomina phaseolina, Fusarium oxysporum, and Fusarium solani with complete reduction of Rhizoctonia solani. Combine use of biocontrol agents in cotton cake amended soil showed maximum positive impact on plant growth, polyphenol concentration and antioxidant activity in okra. PMID- 26373177 TI - Biodiversity of Dominant Cultivable Endophytic Bacteria Inhabiting Tissues of Six Different Cultivars of Maize (Zea mays L. ssp. mays) Cropped under Field Conditions. AB - Endophytic bacteria (EnB) play a crucial role in plant development. This study was an attempt to isolate and identify dominant cultivable EnB inhabiting young seedlings germinated in vitro and leaves of six maize cultivars grown under field conditions at temperate climate zone with culture-dependent approach. We isolated bacteria from field cropped maize only. Strains were identified based on 16S rRNA gene sequencing. In particular, members of Actinobacteria, Bacteroidetes, Firmicutes and alpha- and gamma-Proteobacteria were found. Species of two genus Pseudomonas and Bacillus were dominant among them. Higher diversity of EnB was found in plants collected from Kobierzyce, where we identified 35 species from 16 genera with 22 species uniquely found at this field. On the contrary, from maize leaves collected at Smolice we identified 24 species representing 10 genera with 10 species uniquely isolated from this field. However, none of species was common for all cultivars at both locations. Among isolated EnB six species only, Pseudomonas clemancea, Pseudomonasfluorescens, Bacillus megaterium, Bacillus simplex, Arthrobacter nicotinovorans and Arthrobacter nitroguajacolicus, were found in aboveground parts of the same cultivar grown on both tested fields. The fact that the same cultivars, sown from the same lots of seeds, under field conditions on two different locations were colonized with noticeably different associations of cultivable EnB suggest that cultivar genotype is an important factor selecting endophytic bacteria from local agro-environment. To our knowledge this is first report about the significant variation of diversity of cultivable endophytic bacteria inhabiting aboveground parts of the same maize cultivars grown at different locations. PMID- 26373178 TI - Characterisation of Yersinia Secretion Apparatus--Pathogenicity Island (Ysa-PI) of Yersinia enterocolitica 1B/O8 in Poland: an Idle Ysa is a Specific Hallmark of the Epidemic Sensu Stricto Strain. AB - Yersinia secretion apparatus (Ysa), the chromosomal type three secretion system (T3SS) is considered to contribute to virulence of high-pathogenicity Yersina enterocolitica biovar 1B. DNA-sequence of Ysa pathogenicity island was determined for clinical isolate DM0110 of Y enterocolitica 1B/08 with origin in Poland. We found a premature stop-codon in the regulatory gene ysrR (mutation at position 269). Altered ysrR was detected in all tested 78 isolates of Y enterocolitica 1B/O8 collected from clinical samples in Poland from 2004 to 2013. Since aberrations in YsrR are considered to inactivate Ysa, our findings may suggest Ysa is not indispensable for Y enterocolitica 1B/O8 to infect humans. PMID- 26373179 TI - Immunomodulatory Effect of beta-Glucan on Peritoneal Macrophages of Bab1/c Mice. AB - We assessed the effect of beta-Glucan on macrophages by Griess reagent and viability by MTT assay and cytotoxicity. Assay of macrophages culture supernatants were carried out on WEHI-164 fibrosarcoma cell line as tumor necrosis factor-alpha bioassay were done. NO release was increased at the dose of 10 ug/ml (P = 0.001) of beta-Glucan while the viability of macrophages in all concentrations was the same. In TNF-alpha bioassay, the supernatant of macrophages stimulated with beta-Glucan had a significant cytotoxic effect on WEHI-164 cells (P = 0.023). beta-Glucan had a positive effect on increasing tumoricidal activity of macrophages which may help in anti-cancer immune responses. PMID- 26373180 TI - Bacterial Diversity and Abundance in Shell Biofilms from the Freshwater Snail Pleurocera canaliculatum (Cerithioidea: Pleuroceridae). AB - Mollusk shells provide a hard substrate for aquatic biofilm colonization. While most work has focused on bivalve shells and grazing, little work has focused on gastropod shells and the microbes growing on them. We sampled biofilms from 14 Pleuroceracanaliculatum and analyzed them using a metagenomic approach. Microbial diversity varied between individuals, and rarefaction suggested that 63 snails would need to be sampled to capture all of the estimated genus-level diversity. Cyanobacteria and species of Novosphingobium and Methylosoma were the most abundant taxa across all shells. PMID- 26373181 TI - Isolation and Antimicrobial Testing of Aeromonas spp., Citrobacter spp., Cronobacter spp., Enterobacter spp., Escherichia spp., Klebsiella spp., and Trabulsiella spp. from the Gallbladder of Pigs. AB - The presence of Gram-negative bacteria species, other than Salmonella spp., in the gallbladder of pigs was examined. Isolated Gram-negative bacteria were assigned to species using the MicrogenTM GnA+B-ID Systems. Of the 64 isolated strains 43 were identified as Escherichia coli, seven as Enterobacter spp., three each as Klebsiella spp., Citrobacterfreundii, Aeromonas hydrophila and Cronobacter sakazakii and one each as Escherichiafergusonii and Trabulsiella guamensis. Their antibiograms showed very high resistance to ampicillin, amoxicillin, tetracycline, chloramphenicol and sulfamethoxazole/trimethoprim. It was concluded that the pigs' gallbladder is a reservoir of potentially pathogenic Gram-negative bacteria for pork consumers. PMID- 26373182 TI - Foreword. Health care high quality, sustainability and safety legislation in Japan's health care system. PMID- 26373183 TI - Hospitals Must Select Management Strategies and Make the Kind of Decisions that will Achieve their Goals. PMID- 26373184 TI - The Importance of a Rigorous Root Cause Analysis (RCA) for Healthcare Sentinel Events. PMID- 26373185 TI - A Healthcare Economist's View of Abenomics: Can "Gambling" Economic Policy Work? PMID- 26373186 TI - Risk Factors and Social Background Associated with Suicide in Japan: A Review. AB - AIM: This study examines, from multiple perspectives, the risk factors associated with, and the social background of, individuals committing suicide in Japan. Effective suicide prevention measures are also proposed. METHOD: An analysis of the risk factors for suicide, including the social background of suicide victims, suicide statistics, municipality surveys, interview surveys with bereaved families, mental health surveys, occupational injury inspections, and social resources available to victims, was conducted in the present study. RESULTS: Histories of both mental illnesses (especially depression) and previous suicide attempts are high-risk factors for suicide. Abuse and experience of violence were the remote causes of suicide. On average, more than three crisis factors were present prior to suicide. For example, overwork, problems with human relations, physical/mental disease, and poverty could form a chain that leads to suicide, regardless of gender. More than 40% of suicide attempts were the result of prescription medication overdose. Overall, 70-90% of suicide victims had medical treatment or an expert consultation before death. Staff and financial backing for voluntary telephone consultation were insufficient. Meanwhile, psychiatric social workers could not provide adequate services. CONCLUSIONS: Help seeking is the basis for suicide prevention. In addition to medication management and reducing work hours, communication with caregivers and healthcare providers as well as intervention for the prevention and treatment of mental illness are essential to suicide prevention. Psychotherapy by clinical psychologists is highly recommended. Active placement of psychiatric social workers for telephone consultations and for emergency hospitals' staff at the expense of the government will reduce suicides, suicide attempts, and the human and financial burden on hospitals. PMID- 26373187 TI - Let's Laugh to Cure Diseases. PMID- 26373188 TI - A Study on the Cost of Issuing Social Healthcare Corporation Bonds. AB - The "Social Healthcare Corporation" system was established on 1 April 2007 as a result of the revised Japanese Medical Care Law. As of 1 October 2014, 234 corporations are certified Social Healthcare Corporations. These corporations are allowed to issue public bonds. However, to this day (1 December 2014), no bonds have been issued. In this paper, we focus on cost analysis with respect to issuing public bonds. PMID- 26373189 TI - [FAUNA AND STRUCTURE OF PARASITE COMMUNITIES OF THE COMMON MINNOW PHOXINUS PHOXINUS IN THE RIVERS OF SOUTHERN YAKUTIA]. AB - In Southern Yakutia, the common minnow hosts 37 species of parasites, including the most numerous groups, such as Infusoria, Myxozoa, and Monogenea. Specific parasites include Myxobolus lomi, Myxobolus mongolicus, Epistylus phoxini, Apiosoma phoxini, Trichodina mira, Paratrichodina phoxini, Gyrodactylus laevis, Gyrodactylus limneus, Gyrodactylus macronychus, Gyrodactylus magnificus, and Diplostomum phoxini. The component parasite communities are characterized by high rates of evenness and diversity, but the low level of dominance. They possess different structure in dependence to specific conditions of their formation. Pollution of the Chulman River with heavy metals and organic wastewater resulted in changes of the structure of parasite communities and replacement of dominants. The characters of chronic damages of gills in the minnow caused by M. lomi have been reported, including deformations of gill arches and filaments, destructions of lamellae, and substitution of the lamellae by parasite's plasmodia. PMID- 26373190 TI - [MORPHOLOGICAL VARIABILITY OF PROTEOCEPHALUS PERCAE (MULLER 1780) PARASITIZING COREGONID FISHES]. AB - Morphological variability of Proteocephalus percae from native host--perch Perca fluviatilis and two species of coregonids (whitefish Coregonus lavaretus and Arctic cisco C. autumnalis) from fish farms of Karelia were studied. Parasite groups from 3 host species differed by morphometric parameters. Morphological structure of P. percae from native host included three morphs, those numbers were almost equal. Parasite groups of whitefish and Arctic cisco differed from that of perch in morphological structure and dominance of different morphs. Changes of the P. percae morphological structure was related to differences in ecological niches of three hosts of parasite. This reflects the initial stages of microevolution. The results obtained allow us to estimate an adaptive response of parasitic worms to new host species settling to pond. PMID- 26373192 TI - [THE EMISSION OF PLAGIORCHIS MULTIGLANDULARIS CERCARIAE FROM NATURALLY INFECTED SNAILS LYMNAEA STAGNALIS IN CHANY LAKE, SOUTH OF WEST SIBERIA]. AB - The daily cercarial output of freshwater trematode Plagiorchis multiglandularis from naturally infected snail Lymnaea stagnalis were studied. The snails were collected in the Chany Lake (South of West Siberia). The daily cercarial output from the snail of different size was determined. The average daily cercarial output ranged from 4641 +/- 1829 at the snail with shell length 29 mm to 14022 +/ 5198 at the snail with shell length 44 mm. The positive correlation between the average daily cercarial output and the shell of snail host was found (p <= 0.001). The maximum of P. multiglandularis cercariae release from the snail during daytime, that coincided with period of activity of the second intermediate hosts. Temperature-mediated increase in cercarial output of P. multiglandularis in temperature range 23-24.5 degrees C was found. The cercarial output was inhibited over the temperature optimum. PMID- 26373191 TI - THE FIRST RECORD OF DIMEROSACCUS ONCORHYNCHI (TREMATODA: OPECOELIDAE) IN FISHES FROM RIVERS OF PRIMORSKY TERRITORY, RUSSIA, WITH A DISCUSSION ON ITS TAXONOMIC POSITION USING MORPHOLOGICAL AND MOLECULAR DATA. AB - The opecoelid trematode Dimerosaccus oncorhynchi (Eguchi, 1931) Shimazu, 1980, hitherto known only from the Japanese archipelago, has been found in three species of freshwater salmonid fish (Oncorhynchus masou, Brachymystax tumensis, Salvelinus curilus) from rivers of Primorsky Territory, the Sea of Japan basin, Russia. This is the first record of the parasite in the continental part of Asia. Fishes B. tumensis and S. curilus are new hosts for D. oncorhynchi. The ecological notes, morphological description and drawings of the found trematodes clarifying the morphology of the male reproductive system are given. In the present study phylogenetic relationships of the species D. oncorhynchi with the related taxa were revealed using partial sequences of the 28S rDNA. Obtained results indicate the validity of D. oncorhynchi as the member of the subfamily Opecoelinae, which was closely related to the genus Opecoeloides, a representative of this subfamily. PMID- 26373193 TI - [SEASONAL CHANGES IN THE BIOLOGY OF LEUCOCHLORIDIUM PARADOXUM (TREMATODA, LEUCOCHLORIDIOMORPHIDAE)]. AB - Infection of molluscs Succinea putris by trematodes Leucochloridium paradoxum was studied in the region of Vyritsa (Leningrad Province) during the period of 2008 2014. On the basis of the obtained data, seasonal dynamics of infection of molluscs can be presented as follows. Infection of S. putris occurs during the whole warm period from May to August. Young sporocysts of L. paradoxum overwinter and the metacercariae that develop in their extensions mature during spring becoming infective for birds. In the second half of summer, sporocysts start degenerating and die in late August-September. Each sporocyst can form 2-3 mature broodsacs (maximum 5) simultaneously. In cases of multiple infections, their number can reach 19. Several cases of independent release of sporocysts from molluscs were observed. They survive in environment for about an hour, retaining the ability to infect definitive hosts. Additionally, birds can be infected by pecking of horns of infected snails. PMID- 26373194 TI - [THE MOSQUITOES (DIPTERA, CULICIDAE) OF THE KIROV REGION]. AB - It analyzed the data of mosquitoes caching on the Kirov region area. The habitat distribution and species diversity are analyzes. The checklist includes 25 species. PMID- 26373195 TI - [Tofik Karrarovich Mikailov (15.01.1931-17.12.2014)]. PMID- 26373196 TI - [Nikolay Martem'janovich Pronin (1941-2015)]. PMID- 26373197 TI - An overview on the Effects of 10% and 15% Carbamide Peroxide and its Relationship to Dentine Sensitivity. AB - The purpose of this overview was to review the available literature to determine if there was any evidence that the application of 10% and 15% carbamide peroxide in tooth whitening procedures resulted in tooth (dentine) sensitivity. The conclusions from the review would indicate that tooth whitening with either 10% or 15% carbamide peroxide is an effective and safe treatment when under a dental professionals' supervision. Reported side-effects were considered mild to moderate in nature and were transient in duration. Reported incidences of dentine sensitivity range from 15-65% of patients using 10% carbamide peroxide. PMID- 26373198 TI - Comparison of Flexural Strength of Resin Cements After Storing in Different Media and Bleaching Agents. AB - The aim of this study was to determine the effects of different storage media and bleaching treatments on the flexural strength of two resin cements (Panavia and BisCem). One hundred rectangular-shaped specimens were prepared with two resin cements and were stored in five media types (n = 10): distilled water (DW), lactic acid (LA), sodium hydroxide (NH), in-office bleaching (OB) and home bleaching (HB). There was significant interaction between the solutions and cements (p < 0.05). The lowest three-point flexural strength was found in sodium hydroxide for both cements (p < 0.05). Both cements exhibited significant increase in flexural strength following home and in-office bleaching (except Panavia in OB) (p < 0.05) compared with immersion in distilled water. Panavia recorded significantly higher flexural strength compared with BisCem in all media (p < 0.002), with the exception of in-office bleaching. PMID- 26373199 TI - Load-Bearing Capacity of Fiber-Reinforced Composite Abutments and One-Piece Implants. AB - Fiber-reinforced composites (FRC) can potentially help in a physiologic stress transmission due to its excellent biomechanical matching with living tissues. Novel one-piece FRC implants and abutments with two different fiber orientations were loaded until failure to assess the load-bearing capacity, fracture patterns, and precision of fit. The one-piece FRC implants showed significantly higher load bearing capacity compared to FRC abutments regardless of the fiber orientation (p < 0.001). For FRC abutments, bidirectional abutments showed significantly higher loads compared to unidirectional abutments (p < 0.001). The type of structure and fiber orientation are strong determinant factors of the load-bearing capacity of FRC implants and abutments. PMID- 26373200 TI - Dentures for Randomised Controlled Trials. AB - Making complete dentures for dental research is difficult. The difficulty is not in the construction of dentures, but making sure the clinician is blind to the randomizations, and avoiding confounding variables. For research purposes it is essential that two sets of dentures are similar in every way, apart from the area to be investigated. A previous article showed how to duplicate a lower denture when it was articulated against a single upper denture. This paper describes the additional duplication of upper dentures. These additional problems presented the clinical and technical teams at the Leeds Dental Institute some challenges. PMID- 26373201 TI - A Randomised Controlled Study Comparing the Anterior Mandibular Labio-Lingual Neutral Zone Position in Edentulous Subjects With and Without Their Maxillary Denture In-Situ. AB - Opinion is divided as to whether the neutral zone impression to determine the labio-lingual position of mandibular complete dentures requires the maxillary denture to remain in-situ or not. Two such neutral zone impressions were recorded for each of the 12 participants of this randomised controlled study. The presence of the maxillary denture made no statistically significant mean difference in labio-lingual position of the mandibular neutralzone. Within the confines of this research protocol there was no evidence that the shift in the labio-linguial position of the anterior mandibular neutral zone was consistently affected by the presence of a maxillary appliance. PMID- 26373202 TI - Restorative Case Report: Flexibility of Fibre-Posts. AB - Restoration of an anterior root-filled tooth with little remaining coronal tooth tissue can utilise a post to retain a core, enabling definitive restoration. Post material was, until recently, primarily metal--be it cast or prefabricated. Currently, fibre-posts are promoted as being advantageous due to a favourable failure mechanism which may protect the root from fracture. This Case Report demonstrates failure of the structural integrity of a fibre-post in a maxillary lateral incisor, with a proposed explanation. Retreatment employed a diamond coated ultrasonic tip for removal of the residual fibre-post and restoration with a cast-post and metal ceramic crown. PMID- 26373203 TI - Pharmacogenomics research: a potential strategy for drug development. AB - Adverse drug reactions (ADR) and drug ineffectiveness are the common in clinical practice. Recent studies have indicated their strong connection to the genetic feature of patients. To further illustrate this relationship, the discipline of Pharmacogenomics (PGx) was born. At present, in vitro cell models and in vivo transgenic animal models have a large potential to study the influence of human genetic mutations on drug response. Moreover, PGx guided clinical trials also provide benefits to drug development. With the drug targets introduced by PGx, great success has been achieved in targeted therapy (eg. gefitinib, cetuximab and ado-trastuzumab). Although the progress on PGx research is fascinating, the translation of PGx into drug development is unsatisfactory. To improve this situation, a rounded system that includes individuals, medical staff, academics associations, Government and Pharmaceutics-Biotechnology Industry should be established, as well as a connected pipeline consisting of policy guidance, PGx research, genotyping technology, preclinical and clinical studies. PMID- 26373204 TI - Design, synthesis, and biological evaluation of 2-substituted ethenesulfonic acid ester derivatives as selective PTP1B inhibitors. AB - Fifteen 2-substituted ethenesulfonic acid ester derivatives were designed, synthesized, and evaluated for the inhibitory activities against protein tyrosine phosphatase 1B (PTP1B) and T-Cell protein tyrosine phosphatase (TCPTP). The structural activity relationship (SAR) of these compounds are discussed to clarify the impact of the linker and the optimized tail on the inhibitory activity of PTP1B and selectivity over TCPTP. Most of the compounds exhibit excellent inhibitory activities against PTP1B with IC50 values of 1.5-8.9 MUM. SAR analysis reveal that the substituents at the hydrophobic tail significantly alter the inhibitory activity against PTP1 B and selectivity over TCPTP, e.g. compound 5d showed excellent inhibitory activity to PTP1B with IC50 = 7.8 MUM, and -6-fold selectivity over TCPTP. Combined with our previous findings, we confirm that the linker length and the substituted hydrophobic tail have decisive influence on the PTP1B inhibitory activity and selectivity. PMID- 26373205 TI - Dissolution properties of co-amorphous drug-amino acid formulations in buffer and biorelevant media. AB - Co-amorphous formulations, particularly binary drug-amino acid mixtures, have been shown to provide enhanced dissolution for poorly-soluble drugs and improved physical stability of the amorphous state. However, to date the dissolution properties (mainly intrinsic dissolution rate) of the co-amorphous formulations have been tested only in buffers and their supersaturation ability remain unexplored. Consequently, dissolution studies in simulated intestinal fluids need to be conducted in order to better evaluate the potential of these systems in increasing the oral bioavailability of biopharmaceutics classification system class II drugs. In this study, solubility and dissolution properties of the co amorphous simvastatin-lysine, gibenclamide-serine, glibenclamide-threonine and glibenclamide-serine-threonine were studied in phosphate buffer pH 7.2 and biorelevant media (fasted and fed state simulated intestinal fluids (FaSSIF and FeSSIF, respectively)). The co-amorphous formulations were found to provide a long-lasting supersaturation and improve the dissolution of the drugs compared to the crystalline and amorphous drugs alone in buffer. Similar improvement, but in lesser extent, was observed in biorelevant media suggesting that a dissolution advantage observed in aqueous buffers may overestimate the advantage in vivo. However, the results show that, in addition to stability advantage shown earlier, co-amorphous drug-amino acid formulations provide dissolution advantage over crystalline drugs in both aqueous and biorelevant conditions. PMID- 26373206 TI - An in vitro--in silico--in vivo approach in biopharmaceutical drug characterization: metformin hydrochloride IR tablets. AB - The integrated in vitro--in silico--in vivo approach has emerged into a biopharmaceutical toolkit that could accelerate drug development and improve drug product clinical performance in patients. In the present study, the influence of physiologically based media and dynamic dissolution testing on drug release from two metformin hydrochloride immediate release products with proven bioequivalence was tested. Metformin-specific physiologically based pharmacokinetic (PBPK) model was developed based on a range of literature or in silico predicted data using gastrointestinal simulation technology implemented in the Simcyp software package. Various approaches were employed in order to estimate the human effective permeability which was used as input for metformin plasma profile simulation. Influence of the rate and extent of metformin dissolution on drug absorption was evaluated. Both convolution and deconvolution approaches were used in order to establish a correlation between the in vitro and in vivo data. The results obtained indicate that physiologically based dissolution media and glass bead dissolution device exhibit certain advantages over the compendial dissolution apparatus and simple buffers which tended to be over-discriminative. Gastrointestinal simulation technology implemented in the Simcyp Simulator was successfully used in developing drug-specific PBPK model for metformin. Simulations indicate that in vitro dissolution kinetics has no significant effect on metformin absorption, if more than 65% of drug is released in 1 hour. Level A in vitro-in vivo correlation was obtained using both convolution and deconvolution approaches. PMID- 26373207 TI - Species and sex differences in propofol glucuronidation in liver microsomes of humans, monkeys, rats and mice. AB - Propofol (2,6-diisopropylphenol) is a short-acting anesthetic commonly used in clinical practice, and is rapidly metabolized into glucuronide by UDP glucuronosyltransferase (UGT). In the present study, propofol glucuronidation was examined in the liver microsomes of male and female humans, monkeys, rats, and mice. The kinetics of propofol glucuronidation by liver microsomes fit the substrate inhibition model for humans and mice, the Hill model for monkeys, and the isoenzyme (biphasic) model for rats. The K(m), V(max), and CL(int) values of human liver microsomes were 50 MUM, 5.6 nmol/min/mg protein, and 110 MUL/min/mg protein, respectively, for males, and 46 MUM, 6.0 nmol/min/mg protein, and 130 MUL/min/mg protein, respectively, for females. The rank order of the CL(int) or CL(max) (in vitro clearance) values of liver microsomes was mice humans > monkeys > rats (high-affinity phase) rats (low-affinity phase) in both males and females. Although no significant sex differences were observed in the values of kinetic parameters in any animal species, the in vitro clearance values of liver microsomes were males < females in humans, males = females in rats (low-affinity phase), and males > females in monkeys, rats (high-affinity phase), and mice. These results demonstrated that the kinetic profile of propofol glucuronidation by liver microsomes markedly differed among humans, monkeys, rats, and mice, and suggest that species and sex differences exist in the roles of UGT isoform(s), including UGT1A9, involved in its metabolism. PMID- 26373208 TI - Carrier-mediated placental transport of cimetidine and valproic acid across differentiating JEG-3 cell layers. AB - Human choriocarcinoma has been used as a model to study trophoblast transcellular drug transport in the placenta. Previous models had limitations regarding low molecular weight drug transport through the intracellular gap junction. The purpose of this study was to evaluate placental carrier-mediated transport across a differentiating JEG-3 choriocarcinoma cell (DJEGs) layer model in which the intracellular gap junction was restricted. Cimetidine is the substrate of an efflux transporter, breast cancer resistance protein (BCRP). BCRP highly expressed in the placenta, and its function in the DJEGs model was investigated. In addition, the placental drug transport of another efflux transporter, multidrug resistance-associated proteins (MRPs), and an influx transporter, monocarboxylate transporter (MCT), were examined with various substrates. Cimetidine permeated from the fetal side to the maternal side at significantly high levels and saturated in a dose-dependent manner. The permeability coefficient of a MRP substrate, fluorescein, across the DJEGs model was significantly increased by inhibiting MRP function with probenecid. On the other hand, permeation in the influx direction to the fetal side with a substrate of MCT, valproic acid, had a gentle dose-dependent saturation. These findings suggest that the DJEGs model could be used to evaluate transcellular placental drug transport mediated by major placental transporters. PMID- 26373209 TI - Influence of imatinib at a low dose and sildenafil on pulmonary hypertension in rats. AB - The study investigates whether combination therapy of sildenafil with imatinib at a low dose (20 mg/kg) further ameliorates pulmonary hypertension (PH) in rats. The effects on right ventricle pressure (RVP), and right ventricle hypertrophy (RVH) were assessed in experimental monocrotaline (MCT)-induced pulmonary hypertension. Combined therapy reversed the MCT-induced increase in RVP more than each drug alone and decreased RV hypertrophy (RV/LV+ S ratio), significantly. Such additive effects toward improvement of PH may result from both pharmacodynamic and pharmacokinetic drug-drug interactions, however, further studies are required to assess its mechanistic background. PMID- 26373210 TI - Effects of single nucleotide polymorphisms and haplotypes of the SLCO1B1 gene on the pharmacokinetic profile of atorvastatin in healthy Macedonian volunteers. AB - OATP1B1 is an influx transporter known to mediate the uptake of various endogenous compounds and xenobiotics. Several sequence variations have been discovered in the SLCO1B1 gene encoding OATP1B1. The aim of this study was to investigate the effects of SLCO1B1 polymorphisms on the pharmacokinetics of atorvastatin in healthy volunteers of Macedonian origin. Twenty three participants, genotyped for SLCO1B1 c.388A > G, c.521T > C, c.571T > C, c.597C > T, c.1086C > T, c.1463G > C and c.*439T > G polymorphisms using TaqMan allelic discrimination assay, ingested a single 80 mg dose of atorvastatin. The plasma concentrations of atorvastatin were measured for 48 h using Tandem Liquid Chromatography-Mass Spectrometry, LC-MS-MS, and the peak plasma concentration (C(max)), time to peak plasma concentration (T(max)), elimination half-life (t1/2), constant rate of elimination (k(el)), mean residence time (MRT, expo), volume of distribution (Vd/kg), clearance (CL/kg), area under curve AUC(0.48h) and AUC(0-infinity), were determined. Our data confirmed that the SLCO1B1 gene is highly polymorphic, with a frequency of the c.521T > C single-nucleotide polymorphism (SNP) being the lowest (app. 15%) and of all other SNPs alleles above 40%. Exceptions were c.1463G > C and c.1086C > T SNPs for which variant alleles were not identified. The strongest correlation was observed between the c.521T > C and c.571T > C SNPs pair. The haplotype analysis revealed 10 different haplotypes, with *1J/*1K/*1L being the dominant, with a frequency of app. 40%. The haplotype *15/*16/*17, containing both variant alleles of the functionally most distinguished SNPs, c.388A > G and c.521T > C, occurred with a frequency of 13%. However, *15/*16/*17 homozygotes were not identified in the study group. In this study, no significant differences in the k(el), t1/2, C(max), T(max), AUC(0 48h), AUC(0-infinity), MRT expo, Vd and CL between the carriers of different c.388A > G, c.597C > T and c.*439T > G genotypes were observed. Subject with a variant allele C in the c.521T > C SNP, c.521CC genotype, had markedly higher values for C(max) and AUC(0.48h), 140% and 67%, respectively, in comparison with the carriers of the c.521TT genotype. Also, the carriers of the variant allele C at c.571T > C SNP, c.571 CC genotype, had 55% and 43% lower mean C(max) and AUC(0 48h) in comparison with the carrier of c.571TT. These differences lacked statistical significance due to the size of the sample. In addition, no significant differences in the pharmacokinetic parameters of atorvastatin between the *15/*16/*17 heterozygotes and *15/*16/*17 non-carriers were observed. In conclusion, this extensive analysis of the effect of SLCO1B1 polymorphisms on the pharmacokinetic profile of atorvastatin showed that c.521T > C and c.571T > C SNPs may affect the inter-individual response to atorvastatin. Additional studies, with a large sample size, are needed to confirm this finding. PMID- 26373211 TI - Effects of antidiabetes drugs on functional independence measure on a subacute rehabilitation ward for stroke patients. AB - It has been reported that the improvement of activities of daily living (ADL) by rehabilitation affects glycemic control. However, there are no reports about antidiabetes drugs as factors affecting the outcomes of rehabilitation. Therefore, we investigated the effects of antidiabetes drugs on functional independence measure (FIM) [total (T), motor (M), and cognition (C) items] in stroke patients with diabetes who were discharged from the subacute rehabilitation ward. We chose the frequently used antidiabetes drugs [sulfonylurea (SU), dipeptidyl peptidase-IV inhibitors (DPP-IVIs), and alpha glycosidase inhibitors (alpha-GIs)] as the basis for categorizing the patients. We compared the patients' background features and laboratory data among the three groups. As a result, when SU was used in stroke patients with diabetes, it is difficult to obtain significant FIM-M gain, FIM-C gain, FIM-M efficiency, and FIM C efficiency compared with of-GIs. As a reason for this, we hypothesize the possibility of the involvement of insulin resistance. Therefore, we consider that insulin resistance should be determined early and that it is important to reduce insulin resistance comprehensively by involving experts. PMID- 26373212 TI - Analysis of factors affecting time in therapeutic range control after warfarin administration. AB - The protective efficacy of warfarin for cardiogenic cerebral embolism has been established. However, warfarin is generally administered to only approximately 35% of the atrial fibrillation patients who required warfarin therapy. It has been reported that international normalized ratio (INR) control was carried out appropriately in < 50% of such patients. Therefore, from the viewpoint of prevention of the onset and recurrence of embolism, the maintenance of a stable anticoagulant level is necessary. In warfarin therapy, in addition to INR control, time in therapeutic range (TTR) also markedly affects the efficacy of warfarin therapy. Therefore, we classified patients into two groups on the basis of the cutoff TTR >= 65% at which the inhibitory effect of warfarin on stroke has been observed. We aimed to examine the association between INR and TTR with the correction of the therapeutic efficacy of warfarin by analyzing the factors leading to poor TTR control. The most valuable finding of this study is that marked fluctuations of brain natriuretic peptide levels in patients with complication of heart failure was a risk factor for poor TTR control. Identification of the factors leading to the poor TTR control is useful for making the decision to switch to other anticoagulants, such as dabigatran or apixaban, or to continue warfarin by correcting risk factors in atrial fibrillation patients receiving long-term warfarin therapy. PMID- 26373213 TI - A Study of Operator Performance for a Mechanical Sweet Cherry Harvester: Comparison between Manual and Remote-Controlled Operation. AB - An experimental mechanical sweet cherry harvester was upgraded by changing its rapid impact mechanism to a continuous impact mechanism, in which an end effector (impactor) is positioned on fruit-loaded branches to transfer vibrational energy for fruit removal, and by adding remote control capability. Before the upgrade, the operator was seated at the rear of the harvester to manually control its operation. Adding remote control capability allowed operator mobility while operating the machine. This mobility was aimed at improving operator performance in harvesting cherries. In this study, the performances of the manual and remote operator were compared in terms of the field of view for perceiving target branches, the accuracy of hitting a target branch, and the ease of maneuvering between tree rows. Several sets of photographs totaling 140 individual photos were taken to assess how easy perceiving target branches was in light and dense foliage from the viewpoint of a manual operator and from multiple viewpoints of a remote operator. The percentages of successful hits on the target branch on the first trial (measure of accuracy in positioning the impactor) and the time taken for each successful hit for the manual and remote operator were recorded. The time to travel approximately 126 m long tree rows was also recorded for the manual and remote operators. On average, the remote operator (rank = 6.5) had better perception of the target branch than the manual operator (rank = 3.7) and was more accurate in positioning the impactor on a target branch (93.3% success rate) than the manual operator (84.4% success rate). Similarly, the remote operator spent 19.9 s of positioning time per branch, which was significantly less than the 23.6 s spent by the manual operator. However, the manual operator had better focus and was numerically faster (1.4 km h(-1)) than the remote operator (1.1 km h(-1)), even though the difference was not statistically significant. Overall, the results suggest that remote operation of the harvester may have a potential advantage over manual operation for achieving higher harvesting rates of sweet cherries. PMID- 26373214 TI - Occupational Health and Safety Issues among Vegetable Farmers in Trinidad and the Implications for Extension. AB - Trinidad has an aged farming population. For a host of reasons, young persons are not entering the agricultural sector; therefore, these aged farmers will continue to be the backbone of the industry. Hence, there is much need for improving the health and safety of the workers within this sector. This first-time study assessed the prevalence of occupational health and safety disorders and discomforts among Trinidad's vegetable farmers in an attempt to understand the extent of the problem within the general farm population. The implications for extension are highlighted, and several recommendations are provided. Small-scale commercial-oriented vegetable farmers (n = 100) from ten of the most populated agricultural areas across Trinidad were surveyed. Results indicated that there was an overall moderate prevalence of occupational injuries among vegetable farmers. Most prevalent were musculoskeletal disorders of the lower back and upper body extremities, watery/burning eyes, skin rashes/itching, headaches, fatigue, dehydration, stress, and injuries attributed to slips and falls. Based on the evidence that a problem exists with health and safety, the extension service can now prepare and deliver programs to educate farmers on the actions necessary to improve their personal health and safety and that of their workers. This type of study has not been done before among farmers in Trinidad. It brings a very important and timely issue to the fore because of the aged farming population. Additionally, since the farmer profile and farming systems are similar in the wider Caribbean, policy makers can take note of the findings and recommendations and embrace actions. PMID- 26373215 TI - A Demonstration Project in New York and Virginia: Retrofitting Cost-Effective Roll-over Protective Structures (CROPS) on Tractors. AB - The NIOSH cost-effective roll-over protective structure (CROPS) demonstration project sought to determine whether three prototype roll-over protective structures (ROPS) designed to be retrofitted on Ford 8N, Ford 3000, Ford 4000, and Massey Ferguson 135 tractors could be installed in the field and whether they would be acceptable by the intended end users (farmers). There were a total of 50 CROPS. demonstrators (25 in New York and 25 in Virginia), with 45 observers attending the New York CROPS demonstrations and 36 observers attending the Virginia CROPS demonstrations, for a total of 70 participants in New York and 61 in Virginia. The oldest retrofitted tractors were 77 to 62 years old, while the newest retrofitted tractors were 40 to 37 years old. The most frequently retrofitted tractor in the CROPS demonstration project was a Ford 3000 series tractor (n = 19; 38%), followed by Ford 4000 (n = 11; 22%), Massey Ferguson 135 (n = 11; 22%), and Ford 8N (n = 9; 18%). A major issue of CROPS retrofitting was the rear wheel fenders. The effort involved in disassembling the fenders (removing the old bolts was often faster by cutting them with a torch), modifying the fender mounting brackets, and then reinstalling the fenders with the CROPS generally required the most time. In addition, various other semi-permanent equipment attachments, such as front-end loaders, required additional time and effort to fit with the CROPS. Demonstrators were asked to rank the reasons why they had not retrofitted their tractors with ROPS until they had enrolled in the CROPS demonstration program. ROPS "cost too much" was ranked as the primary reason for participants in both states (80% for New York and 88% for Virginia). The second highest ranked reasons were "ROPS wasn't available" for Virginia (80%) and "hassle to find ROPS" for New York (69%). The third highest ranked reasons were "not enough time to find ROPS" for New York (67%) and "hassle to find ROPS" for Virginia (79%). All demonstrators and observers indicated that they were glad to have participated in the CROPS project. PMID- 26373216 TI - Fish Hatchery Noise Levels and Noise Reduction Techniques. AB - This study examined occupational noise within two rearing facilities at a production fish hatchery and evaluated two simple noise reduction techniques. Ambient noise levels in the hatchery tank room ranged from 50 dB in the absence of flowing water to over 73 dB when water was flowing to all 35 tanks under typical hatchery operating procedures. Covering the open standpipes did not significantly reduce noise levels. However, placing partial tank covers over the top of the tanks above the water inlet significantly reduced noise levels, both with and without the use of standpipe covers. Noise levels in the salmon building rose from 43.2 dB without any flowing water to 77.5 dB with water flowing to all six in-ground tanks. Significant noise reductions were observed when the tanks were completely covered or with standpipe covers. Decibel levels showed the greatest reduction when the tanks and standpipes were both covered. These results indicate that occupational noise levels in aquaculture environments may be reduced through the use of simple and relatively inexpensive techniques. PMID- 26373217 TI - Be Strong. PMID- 26373218 TI - Home Alone. PMID- 26373219 TI - Believing without seeing. PMID- 26373220 TI - Stripped-down savings. PMID- 26373221 TI - State of safety. PMID- 26373222 TI - Your Food. PMID- 26373223 TI - Evaluation of the Antibacterial Effect of Silver Nanoparticles on Guided Tissue Regeneration Membrane Colonization--An in Vitro Study. AB - OBJECTIVE: The aim of this in vitro study was to investigate the colonization and penetration of specific bacteria on nanosilver-impregnated GTR (guided tissue regeneration) membranes. METHODS: Three sets of GTR membranes were used in this study: 1) GTR-C: Plain GTR membrane as a negative control; 2) GTR-NS: GTR membrane impregnated with silver nanoparticles as the test group; 3) GTR-DOX: GTR membrane impregnated with 25% (w/w) doxycycline hydrochloride acting as a positive control. Stress-strain characteristics were calculated to determine the physical properties of the control and impregnated membranes. Qualitative observation of microbial adherence and bacterial penetration through GTR membranes were performed by using four organisms (Streptococcus mutans, Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum and Porphyromonas gingivalis) reported to have strong adherent capabilities to collagen membranes. RESULTS: The mean bacterial adherence scores were significantly greater (p < 0.001) in the GTR-C group when compared to GTR-DOX and GTR-NS groups. GTR-NS showed lower adherence scores than GTR-DOX across all four microorganisms; this difference, however was not statistically significant. The difference in colony forming units (CFUs) was highly significant (p < 0.001), suggesting greater penetration in GTR-C membranes when compared to GTR-NS and GTR-DOX groups. Though the mean CFUs were lower in GTR-DOX than in GTR-NS across all four microorganisms, this difference was statistically significant only for S. mutans and F. nucleatum. CONCLUSION: The incorporation of silver nanoparticles may be of value when controlling membrane-associated infection. Studies with different nanosilver particle sizes should be conducted to further evaluate the beneficial properties of nanosilver against periodontal pathogens. PMID- 26373225 TI - Local Drug Delivery Systems in the Treatment of Periodontitis: A Literature Review. AB - In order to complement non-surgical therapy in periodontitis, there are multiple options of antimicrobials, such as metronidazole, chlorhexidine, minocycline, doxycycline and tetracycline, which can be locally delivered into the mucosa. These drugs are used in periodontal pockets and can inhibit or eliminate periodontopathogenic microorganisms as well as modulate the inflammatory response of tissues. However, limited data are available concerning the relationship between effect, efficacy and clinical status of the periodontium. This review aims to evaluate the effect and the efficacy of five types of local drug delivery systems in clinical parameters of periodontology. Researched papers using MEDLINE via PubMed, and LILACS databases related to five types of local drug delivery systems as chlorhexidine gluconate, doxycycline hyclate, metronidazole gel, minocycline ointment and tetracycline fibers, were reviewed aiming to address the mechanism of action and the evidence of clinical effectiveness of adjunctive use of these antimicrobials following surgical and/or non-surgical therapies. Inclusion criteria defined that articles must be randomized controlled trials performed in humans and published between 1996 and 2014. The adjunctive use of local drug delivery systems with controlled release properties may provide a defined, but limited, beneficial response on periodontal pockets. Furthermore, local drug delivery as an active treatment or maintenance therapy depends on clinical findings, responses to treatment described in the literature, desired clinical outcomes, and patients' dental and medical histories, including their past usage of antimicrobials. PMID- 26373224 TI - Management of Gingival Overgrowth in a Cardiac Transplant Patient Using Laser Assisted Gingivectomy/Gingivoplasty. AB - Drug-induced gingival overgrowth (DIGO) is an oral clinical manifestation associated with certain medications such as immunosuppressants that are administered to organ transplant patients to prevent graft rejection. In patients with cardiac transplants, management of DIGO is critical. In such patients, plaque biofilm accumulation at the gingival interface might be detrimental as it may lead to transient bacteremia as well as systemic inflammation resulting in thromboembolic events. This case report describes the management of DIGO in a cardiac transplant recipient by change of immunosuppressant medication, non surgical periodontal therapy and laser-assisted gingivectomy. PMID- 26373226 TI - Effect of Cinnamon Extract and Chlorhexidine Gluconate (0.2%) on the Clinical Level of Dental Plaque and Gingival Health: A 4-Week, Triple-Blind Randomized Controlled Trial. AB - AIM: To compare the effect of cinnamon extract, chlorhexidine mouthwash and placebo on dental plaque level and gingivitis. MATERIALS AND METHODS: One hundred five healthy dental and medical students aged 21 to 25 years participated in the study. The subjects were randomly divided into three groups: i.e., the cinnamon group, the chlorhexidine gluconate mouthwash group and the placebo (distilled water) group. Data were collected at baseline, the 15th and the 30th day. Plaque was disclosed using erythrosine disclosing agent and scores were recorded using the Quigley and Hein plaque index modified by Turesky-Gilmore-Glickman. Gingival scoring was done by the gingival index of Loe and Silness. Statistical analysis was carried out to compare the effect of all three treatments groups; p <= 0.05 was considered statistically significant. RESULTS: The chlorhexidine group showed the maximum decrease in both plaque and gingival scores, followed by cinnamon extract, but the result was statistically insignificant. The plaque and gingival scores remained almost unchanged in the distilled water group. Conclusion: The results of the present study indicate that cinnamon may prove to be an effective agent owing to its ability to reduce plaque level and gingivitis. PMID- 26373228 TI - Cerebral multifrequency MR elastography by remote excitation of intracranial shear waves. AB - The aim of this study was to introduce remote wave excitation for high-resolution cerebral multifrequency MR elastography (mMRE). mMRE of 25-45-Hz drive frequencies by head rocker stimulation was compared with mMRE by remote wave excitation based on a thorax mat in 12 healthy volunteers. Maps of the magnitude |G*| and phase phi of the complex shear modulus were reconstructed using multifrequency dual elasto-visco (MDEV) inversion. After the scan, the subjects and three operators assessed the comfort and convenience of cerebral mMRE using two methods of stimulating the brain. Images were acquired in a coronal view in order to identify anatomical regions along the spinothalamic pathway. In mMRE by remote actuation, all subjects and operators appreciated an increased comfort and simplified procedural set-up. The resulting strain amplitudes in the brain were sufficiently large to analyze using MDEV inversion, and yielded high-resolution viscoelasticity maps which revealed specific anatomical details of brain mechanical properties: |G*| was lowest in the pons (0.97 +/- 0.08 kPa) and decreased within the corticospinal tract in the caudal-cranial direction from the crus cerebri (1.64 +/- 0.26 kPa) to the capsula interna (1.29 +/- 0.14 kPa). By avoiding onerous mechanical stimulation of the head, remote excitation of intracranial shear waves can be used to measure viscoelastic parameters of the brain with high spatial resolution. Therewith, the new mMRE method is suitable for neuroradiological examinations in the clinic. PMID- 26373229 TI - Super-Resolution Imaging Conditions for enhanced Yellow Fluorescent Protein (eYFP) Demonstrated on DNA Origami Nanorulers. AB - Photostability is one of the crucial properties of a fluorophore which strongly influences the quality of single molecule-based super-resolution imaging. Enhanced yellow fluorescent protein (eYFP) is one of the most widely used versions of fluorescent proteins in modern cell biology exhibiting fast intrinsic blinking and reversible photoactivation by UV light. Here, we developed an assay for studying photostabilization of single eYFP molecules with respect to fast blinking and demonstrated a 6-fold enhanced photostability of single eYFP molecules with a beneficial influence on the blinking kinetics under oxygen removal and addition of aliphatic thiols (dSTORM-buffer). Conjugation to single stranded DNA and immobilization via DNA hybridization on a DNA origami 12 helix bundle in aqueous solution allowed photophyiscal studies of eYFP at the single molecule level and at close to physiological conditions. The benefit of improved photophysical properties for localization-based super-resolution microscopy is demonstrated and quantitatively characterized by imaging 12 helix bundle DNA origami nanorulers with binding sites at designed distances of 160 and 100 nm and by imaging microtubules in fixed mammalian Vero cells. PMID- 26373233 TI - An observational study on work interruptions during medication administration in residential care homes for older people. PMID- 26373236 TI - Increased sialylation as a phenomenon in accommodation of the parasitic nematode Trichinella spiralis (Owen, 1835) in skeletal muscle fibres. AB - The biology of sialic acids has been an object of interest in many models of acquired and inherited skeletal muscle pathology. The present study focuses on the sialylation changes in mouse skeletal muscle after invasion by the parasitic nematode Trichinella spiralis (Owen, 1835). Asynchronous infection with T. spiralis was induced in mice that were sacrificed at different time points of the muscle phase of the disease. The amounts of free sialic acid, sialylated glycoproteins and total sialyltransferase activity were quantified. Histochemistry with lectins specific for sialic acid was performed in order to localise distribution of sialylated glycoconjugates and to clarify the type of linkage of the sialic acid residues on the carbohydrate chains. Elevated intracellular accumulation of alpha-2,3- and alpha-2,6-sialylated glycoconjugates was found only within the affected sarcoplasm of muscle fibres invaded by the parasite. The levels of free and protein-bound sialic acid were increased and the total sialyltransferase activity was also elevated in the skeletal muscle tissue of animals with trichinellosis. We suggest that the biological significance of this phenomenon might be associated with securing integrity of the newly formed nurse cell within the surrounding healthy skeletal muscle tissue. The increased sialylation might inhibit the affected muscle cell contractility through decreased membrane ion gating, helping the parasite accommodation process. PMID- 26373239 TI - Dynamical crossover line in supercritical water. AB - Dynamical crossover in water is studied by means of computer simulation. The crossover temperature is calculated from the behavior of velocity autocorrelation functions. The results are compared with experimental data. It is shown that the qualitative behavior of the dynamical crossover line is similar to the melting curve behavior. Importantly, the crossover line belongs to experimentally achievable (P, T) region which stimulates the experimental investigation in this field. PMID- 26373238 TI - Peripheral blood minimal residual disease may replace bone marrow minimal residual disease as an immunophenotypic biomarker for impending relapse in acute myeloid leukemia. AB - As relapses are common in acute myeloid leukemia (AML), early relapse prediction is of high importance. Although conventional minimal residual disease (MRD) measurement is carried out in bone marrow (BM), peripheral blood (PB) would be an advantageous alternative source. This study aims to investigate the specificity of leukemia-associated immunophenotypes used for MRD detection in blood samples. Consistency of PB MRD as compared with BM MRD was determined in flow cytometric data of 205 paired BM and PB samples of 114 AML patients. A significant correlation was found between PB and BM MRD (r=0.67, P<0.001), while median PB MRD percentage was factor 4-5 lower compared with BM MRD. Primitive blast (CD34+/CD117+/CD133+) frequency was significantly lower in PB (median factor 23.7), indicating that PB MRD detection is more specific than BM. Cumulative incidence of relapse 1 year after induction therapy was 29% for PB MRD-negative and 89% for PB MRD-positive patients (P<0.001). Three-year OS was 52% for MRD negative and 15% for MRD-positive patients (P=0.034). Similar differences were found after consolidation therapy. As PB MRD appeared to be an independent predictor for response duration, the highly specific PB MRD assay may have a prominent role in future MRD assessment in AML. PMID- 26373241 TI - Functional specialization in regulation and quality control in thermal adaptive evolution. AB - Distinctive survival strategies, specialized in regulation and in quality control, were observed in thermal adaptive evolution with a laboratory Escherichia coli strain. The two specialists carried a single mutation either within rpoH or upstream of groESL, which led to the activated global regulation by sigma factor 32 or an increased amount of GroEL/ES chaperonins, respectively. Although both specialists succeeded in thermal adaptation, the common winner of the evolution was the specialist in quality control, that is, the strategy of chaperonin-mediated protein folding. To understand this evolutionary consequence, multilevel analyses of cellular status, for example, transcriptome, protein and growth fitness, were carried out. The specialist in quality control showed less change in transcriptional reorganization responding to temperature increase, which was consistent with the finding of that the two specialists showed the biased expression of molecular chaperones. Such repressed changes in gene expression seemed to be advantageous for long-term sustainability because a specific increase in chaperonins not only facilitated the folding of essential gene products but also saved cost in gene expression compared with the overall transcriptional increase induced by rpoH regulation. Functional specialization offered two strategies for successful thermal adaptation, whereas the evolutionary advantageous was more at the points of cost-saving in gene expression and the essentiality in protein folding. PMID- 26373243 TI - Passing the baton: Mentoring for adoption of active-learning pedagogies by research-active junior faculty. AB - There are barriers to adoption of research-based teaching methods. Professional development workshops may inform faculty of these methods, but effective adoption often does not follow. In addition, newly-minted research-active faculty are often overwhelmed by the many new responsibilities (grant writing, group management, laboratory setup, teaching) that accompany the position and normally do not have the time to consider novel teaching approaches. This case study documents how over a three-year period, the responsibility for teaching a nontraditional "Introduction to Biochemistry" course in a problem-based learning format was successfully transferred from a senior faculty member nearing retirement (HBW) to a newly-hired research-active assistant professor (CLG). We describe our apprenticeship project involving modeling, scaffolding, fading, and coaching. We suggest that involving faculty in active-learning pedagogy early in their career with mentoring by senior faculty overcomes barriers to adopting these methods. This case describes a specific example from which potentially useful elements can be adopted and adapted wherever biochemistry is taught. PMID- 26373246 TI - Penile ulceration: a rare manifestation of cutaneous crohn's successfully treated with subcutaneous methotrexate. PMID- 26373247 TI - The relationship between oral and written narratives: A three-year longitudinal study of narrative cohesion, coherence, and structure. AB - BACKGROUND: The relationship between oral language and the writing process at early acquisition stages and the ways the former can enhance or limit the latter has not been researched extensively. AIMS: The predictive relationship between kindergarten oral narrative competence and the first- and second-grade written narrative competence was explored in a 3-year longitudinal study. Among the first and second graders, the relationship between orthographic competence and narrative competence in written productions was also analysed. SAMPLE: One hundred and nine Italian children participated in this study. MEASURES: Kindergarteners produced an oral narrative, whereas the first and second graders produced a written narrative. The oral and written narratives were analysed in terms of cohesion, coherence, and structure. The first-grade orthographic competence was assessed via a dictation task. RESULTS: Multiple linear regression and mediational analyses were performed. Kindergarten oral narrative competence affected the first- and second-grade written narrative competence via a mediational effect of orthographic competence. CONCLUSION: The results suggest the importance of practicing oral narrative competence in kindergarten and first grade and the value of composition quality independent of orthographic text accuracy. PMID- 26373251 TI - Fluorescent probes for real-time measurement of nitric oxide in living cells. AB - Nitric oxide (NO) is an important signaling molecule in biology. Both NO excess and insufficiency have been implicated in numerous physiological and pathological conditions. In order to study the diverse biological roles of NO in cells and tissues, many techniques have been developed for assaying NO. Recently, new generations of fluorescent probes have become indispensible tools for the study of NO biology because of their sensitivity, selectivity, spatiotemporal resolution, and experimental feasibility. Rational application of these probes in the study requires the understanding of the molecular mechanism that the probes are involved in. In this review, we will present an arsenal of fluorescent probes used to detect NO in living cells and animal tissues. We will also discuss the molecular mechanisms, actualities and prospects of fluorescent probes in detecting NO in cell biology. PMID- 26373252 TI - Commentary on "Transformations in hallucinosis and the receptivity of the analyst" by Civitarese. PMID- 26373254 TI - Dodecyl ethyl dimethyl ammonium bromide capped WO3 nanoparticles: efficient scaffolds for chemical sensing and environmental remediation. AB - The current work revealed the comparative analysis of bare and surface functionalized tungsten trioxide (WO3) nanoparticles that can be successfully utilized as competent photocatalysts for the degradation of organic dyes and as efficient electron transporters for the fabrication of highly sensitive electrochemical sensors in aqueous medium. The room temperature synthesis of WO3 nanoparticles with good crystallinity was carried out in the presence of dodecylethyldimethyl ammonium bromide (DEDMAB) as the template by a wet chemical process. The surface functionalized nanoparticles possess a controllable band gap and act as an effectual substrate for electrochemical sensing of hydrazine. The sensitivity values of the fabricated sensor range from 9.39 MUA MUM(-1) cm(-2) with the limits of detection ranging from 28.8 MUM. Furthermore, surface modulated particles also exhibited enhanced photocatalytic performance in the photodegradation of Congo red dye with an efficiency of 98.67% compared to bare WO3 nanoparticles without any modification. The comparison of the current responses and photodegradation activity of the bare and capped WO3 particles illustrates an excellent sensitivity, selectivity and operational stability of the as-functionalized nanoparticles. PMID- 26373255 TI - Turning the inside out: the microbiology of atopic dermatitis. AB - Allergy is on the rise worldwide. The hygiene hypothesis of atopic diseases linked microbes with atopic dermatitis (AD) both as drivers and modulators of skin pathology. The earlier literature favoured an inside-outside model of AD where an immunological abnormality compounded by a gut microbiota dysbiosis is the primary event. Probiotic intervention trials with lactobacilli and bifidobacteria as well as the application of bifidogenic oligosaccharide prebiotics showed indeed promising clinical results, but no consistent gut microbiota dysbiosis could be linked with AD. An alternative hypothesis known as outside-inside model of AD considers a genetic skin barrier effect compounded by a skin microbiota dysbiosis as primary pathogenic event. Cultivation microbiology has demonstrated strong skin colonization with superantigen-encoding Staphylococcus aureus in AD patients; microbiota and molecular microbiome analyses demonstrated that S. aureus abundance fluctuates and parallels clinical symptoms. In a mouse model, delta-toxin of S. aureus induced mast cell degranulation, leading to AD-like symptoms. Mutant mice developing AD symptoms showed increased skin colonization with S. aureus; antibiotic treatment alleviated the symptoms. Clinical trials showed that various treatments reducing S. aureus skin load also reduced AD symptoms, suggesting S. aureus as a potential critical driver of AD and a target for antimicrobial interventions other than antibiotics. PMID- 26373256 TI - Cyclization of an alpha,beta-unsaturated hydrazone catalyzed by a BINOL phosphoric acid: Pericyclic or not? AB - Density functional theory is used to study the mechanism of the title reaction, one of the first catalytic asymmetric 6pi-electrocyclizations observed experimentally. The benzylideneacetone-derived phenyl hydrazone is chosen as model substrate for the cyclization reaction, both in the protonated (A) and unprotonated (B) form, while the isoelectronic carbon analogue, 1,5 diphenylpentadienyl anion (C), serves as a reference for comparisons. The barrier to cyclization is computed to be more than 15 kcal/mol lower in A compared with B, in line with the observed acid catalysis. The relevant transition states to cyclization are characterized for A and C using orbital inspection, natural bond orbital analysis, nucleus independent chemical shifts, and stereochemical indicators. The cyclization of C is confirmed to be pericyclic, while that of A can be described as pseudopericyclic ring closure involving an intramolecular nucleophilic addition. PMID- 26373257 TI - A dose-response meta-analysis reveals an association between vitamin B12 and colorectal cancer risk. AB - OBJECTIVE: The current meta-analysis evaluated the association between vitamin B12 intake and blood vitamin B12 level and colorectal cancer (CRC) risk. DESIGN: The PubMed and EMBASE databases were searched. A dose-response analysis was performed with generalized least squares regression, with the relative risk (RR) and 95 % CI as effect values. SETTING: The meta-analysis included seventeen studies. SUBJECTS: A total of 10 601 patients. RESULTS: The non-linear dose response relationship between total vitamin B12 intake and CRC risk was insignificant (P=0.690), but the relationship between dietary vitamin B12 intake and CRC risk was significant (P<0.001). Every 4.5 MUg/d increment in total and dietary vitamin B12 intake was inversely associated with CRC risk (total intake: RR=0.963; 95 % CI 0.928, 0.999; dietary intake: RR=0.914; 95 % CI 0.856, 0.977). The inverse association between vitamin B12 intake and CRC risk was also significant when vitamin B12 intake was over a dosage threshold, enhancing the non-linear relationship. The non-linear dose-response relationship between blood vitamin B12 level and CRC risk was insignificant (P=0.219). There was an insignificant association between every 150 pmol/l increment in blood vitamin B12 level and CRC risk (RR=1.023; 95 % CI 0.881, 1.187). CONCLUSIONS: Our meta analysis indicates that evidence supports the use of vitamin B12 for cancer prevention, especially among populations with high-dose vitamin B12 intake, and that the association between CRC risk and total vitamin B12 intake is stronger than between CRC risk and dietary vitamin B12 intake only. PMID- 26373258 TI - Uptake and translocation of imidacloprid, clothianidin and flupyradifurone in seed-treated soybeans. AB - BACKGROUND: Seed treatment insecticides have become a popular management option for early-season insect control. This study investigated the total uptake and translocation of seed-applied [(14) C]imidacloprid, [(14) C]clothianidin and [(14) C]flupyradifurone into different plant parts in three soybean vegetative stages (VC, V1 and V2). The effects of soil moisture stress on insecticide uptake and translocation were also assessed among treatments. We hypothesized that (1) uptake and translocation would be different among the insecticides owing to differences in water solubility, and (2) moisture stress would increase insecticide uptake and translocation. RESULTS: Uptake and translocation did not follow a clear trend in the three vegetative stages. Initially, flupyradifurone uptake was greater than clothianidin uptake in VC soybeans. In V1 soybeans, differences in uptake among the three insecticides were not apparent and unaffected by soil moisture stress. Clothianidin was negatively affected by soil moisture stress in V2 soybeans, while imidacloprid and flupyradifurone were unaffected. Specifically, soil moisture stress had a positive effect on the distribution of flupyradifurone in leaves. This was not observed with the neonicotinoids. CONCLUSIONS: This study enhances our understanding of the uptake and distribution of insecticides used as seed treatments in soybean. The uptake and translocation of these insecticides differed in response to soil moisture stress. (c) 2015 Society of Chemical Industry. PMID- 26373261 TI - HepG2 Cell Resistance against Camptothecin from a Lysosomal Drug Delivery. AB - A galactose-appended drug delivery system released camptothecin (CPT) to lysosomes of HepG2 hepatoma cells, resulting in the cell resistance to the anticancer drug. We found that the resistance to CPT is caused by alteration of the drug release from the prodrug in lysosomes, emphasizing that the final delivery locations may critically influence drug efficacy. PMID- 26373264 TI - Cell signalling: Ciliary phosphoinositides regulate Hedgehog signalling. PMID- 26373262 TI - A new anti-microbial combination prolongs the latency period, reduces acute histologic chorioamnionitis as well as funisitis, and improves neonatal outcomes in preterm PROM. AB - OBJECTIVE: Antibiotic administration is a standard practice in preterm premature rupture of membranes (PROM). Specific anti-microbial agents often include ampicillin and/or erythromycin. Anaerobes and genital mycoplasmas are frequently involved in preterm PROM, but are not adequately covered by antibiotics routinely used in clinical practice. Our objective was to compare outcomes of PROM treated with standard antibiotic administration versus a new combination more effective against these bacteria. STUDY DESIGN: A retrospective study compared perinatal outcomes in 314 patients with PROM <34 weeks receiving anti-microbial regimen 1 (ampicillin and/or cephalosporins; n = 195, 1993-2003) versus regimen 2 (ceftriaxone, clarithromycin and metronidazole; n = 119, 2003-2012). Intra amniotic infection/inflammation was assessed by positive amniotic fluid culture and/or an elevated amniotic fluid MMP-8 concentration (>23 ng/mL). RESULTS: (1) Patients treated with regimen 2 had a longer median antibiotic-to-delivery interval than those with regimen 1 [median (interquartile range) 23 d (10-51 d) versus 12 d (5-52 d), p < 0.01]; (2) patients who received regimen 2 had lower rates of acute histologic chorioamnionitis (50.5% versus 66.7%, p < 0.05) and funisitis (13.9% versus 42.9%, p < 0.001) than those who had received regimen 1; (3) the rates of intra-ventricular hemorrhage (IVH) and cerebral palsy (CP) were significantly lower in patients allocated to regimen 2 than regimen 1 (IVH: 2.1% versus 19.0%, p < 0.001 and CP: 0% versus 5.7%, p < 0.05); and (4) subgroup analysis showed that regimen 2 improved perinatal outcomes in pregnancies with intra-amniotic infection/inflammation, but not in those without intra-amniotic infection/inflammation (after adjusting for gestational age and antenatal corticosteroid administration). CONCLUSION: A new antibiotic combination consisting of ceftriaxone, clarithromycin, and metronidazole prolonged the latency period, reduced acute histologic chorioamnionitis/funisitis, and improved neonatal outcomes in patients with preterm PROM. These findings suggest that the combination of anti-microbial agents (ceftriaxone, clarithromycin, and metronidazole) may improve perinatal outcome in preterm PROM. PMID- 26373267 TI - Signatures of new d-wave vortex physics in overdoped Tl2Ba2CuO(6+x) revealed by TF-u(+)SR. AB - The spontaneous expulsion of applied magnetic field, the Meissner effect, is a defining feature of superconductors; in Type-II superconductors above the lower critical field, this screening takes the form of a lattice of magnetic flux vortices. Using implanted spin-1/2 positive muons, one can measure the vortex lattice field distribution through the spin precession and deduce key parameters of the superconducting ground state, and thereby fundamental properties of the superconducting pairing. Muon spin rotation/relaxation (uSR) experiments have indeed revealed much interesting physics in the underdoped cuprates, where superconductivity is closely related to, or coexistent with, disordered or fluctuating magnetic and charge excitations. Such complications should be absent in overdoped cuprates, which are believed to exhibit conventional Fermi liquid behaviour. These first transverse field (TF)-u(+)SR experiments on heavily overdoped single crystals reveal a superfluid density exhibiting a clear inflection point near 0.5Tc, with a striking doping-independent scaling. This reflects hitherto unrecognized physics intrinsic to d-wave vortices, evidently generic to the cuprates, and may offer fundamentally new insights into their still-mysterious superconductivity. PMID- 26373263 TI - Centrosome function and assembly in animal cells. AB - It has become clear that the role of centrosomes extends well beyond that of important microtubule organizers. There is increasing evidence that they also function as coordination centres in eukaryotic cells, at which specific cytoplasmic proteins interact at high concentrations and important cell decisions are made. Accordingly, hundreds of proteins are concentrated at centrosomes, including cell cycle regulators, checkpoint proteins and signalling molecules. Nevertheless, several observations have raised the question of whether centrosomes are essential for many cell processes. Recent findings have shed light on the functions of centrosomes in animal cells and on the molecular mechanisms of centrosome assembly, in particular during mitosis. These advances should ultimately allow the in vitro reconstitution of functional centrosomes from their component proteins to unlock the secrets of these enigmatic organelles. PMID- 26373268 TI - Wound-care teams for preventing and treating pressure ulcers. AB - BACKGROUND: Pressure ulcers, which are localised injury to the skin or underlying tissue, or both, occur when people are unable to reposition themselves to relieve pressure on bony prominences. Pressure ulcers are often difficult to heal, painful and impact negatively on the individual's quality of life. The cost implications of pressure ulcer treatment are considerable, compounding the challenges in providing cost effective, efficient health service delivery. International guidelines suggest that to prevent and manage pressure ulcers successfully a team approach is required. Therefore, this review has been conducted to clarify the role of wound-care teams in the prevention and management of pressure ulcers. OBJECTIVES: To assess the impact of wound-care teams in preventing and treating pressure ulcers in people of any age, nursed in any healthcare setting. SEARCH METHODS: In April 2015 we searched: The Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE and EBSCO CINAHL. There were no restrictions with respect to language, date of publication or study setting. SELECTION CRITERIA: We considered RCTs that evaluated the effect of any configuration of wound-care teams in the treatment or prevention of pressure ulcers. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed titles and, where available, abstracts of the studies identified by the search strategy for their eligibility. We obtained full versions of potentially relevant studies and two review authors independently screened these against the inclusion criteria. MAIN RESULTS: We identified no studies that met the inclusion criteria. AUTHORS' CONCLUSIONS: We set out to evaluate the RCT evidence pertaining to the impact of wound-care teams on the prevention and management of pressure ulcers. However, no studies met the inclusion criteria. There is a lack of evidence concerning whether wound-care teams make a difference to the incidence or healing of pressure ulcers. Well-designed trials addressing important clinical, quality of life and economic outcomes are justified, based on the incidence of the problem and the high costs associated with pressure ulcer management. PMID- 26373269 TI - Pyrrolizidine alkaloids in food and feed on the Belgian market. AB - Pyrrolizidine alkaloids (PAs) are widely distributed plant toxins with species dependent hepatotoxic, carcinogenic, genotoxic and pneumotoxic risks. In a recent European Food Safety Authority (EFSA) opinion, only two data sets from one European country were received for honey, while one feed data set was included. No data are available for food or feed samples from the Belgian market. We developed an LC-MS/MS method, which allowed the detection and quantification of 16 PAs in a broad range of matrices in the sub ng g(-1) range. The method was validated in milk, honey and hay and applied to honey, tea (Camellia sinensis), scented tea, herbal tea, milk and feed samples bought on the Belgian market. The results confirmed that tea, scented tea, herbal tea and honey are important food sources of pyrrolizidine alkaloid contamination in Belgium. Furthermore, we detected PAs in 4 of 63 commercial milk samples. A high incidence rate of PAs in lucerne (alfalfa)-based horse feed and in rabbit feed was detected, while bird feed samples were less contaminated. We report for the first time the presence of monocrotaline, intermedine, lycopsamine, heliotrine and echimidine in cat food. PMID- 26373270 TI - Comparison of availability and plasma clearance rates of beta-hydroxy-beta methylbutyrate delivery in the free acid and calcium salt forms. AB - beta-Hydroxy-beta-methylbutyrate (HMB), a leucine metabolite, has long been supplemented as a Ca salt (Ca-HMB) to increase strength and performance gains with exercise and to reduce recovery time. Recently, the free acid form of HMB (HMB-FA) has become commercially available in capsule form (gelcap). The current study was conducted to compare the bioavailability of HMB using the two commercially available capsule forms of HMB-FA and Ca-HMB. We also compared the pharmacokinetics of each form when administered mixed in water. Ten human subjects (five male and five female) were studied in a randomised crossover design. There was no significant sex by treatment interaction for any of the pharmacokinetic parameters measured. HMB-FA administered in capsules was more efficient than Ca-HMB capsule at HMB delivery with a 37 % increase in plasma clearance rate (74.8 (sem 4.0) v. 54.5 (sem 3.2) ml/min, P<0.0001) and a 76 % increase in peak plasma HMB concentration (270.2 (sem 17.8) v. 153.9 (sem 17.9) MUmol/l, P<0.006), which was reached in one-third the time (P<0.009). When HMB-FA and Ca-HMB were administered in water, the differences still favoured HMB-FA, albeit to a lesser degree. Plasma HMB with HMB-FA administered in water was greater during the early phase of absorption (up to 45 min postadministration, P<0.05); this resulted in increased AUC during the first 60 min after administration, when compared with Ca-HMB mixed in water (P<0.03). In conclusion, HMB-FA in capsule form improves clearance rate and availability of HMB compared with Ca-HMB in capsule form. PMID- 26373265 TI - Epigenetic regulation of ageing: linking environmental inputs to genomic stability. AB - Ageing is affected by both genetic and non-genetic factors. Here, we review the chromatin-based epigenetic changes that occur during ageing, the role of chromatin modifiers in modulating lifespan and the importance of epigenetic signatures as biomarkers of ageing. We also discuss how epigenome remodelling by environmental stimuli affects several aspects of transcription and genomic stability, with important consequences for longevity, and outline epigenetic differences between the 'mortal soma' and the 'immortal germ line'. Finally, we discuss the inheritance of characteristics of ageing and potential chromatin based strategies to delay or reverse hallmarks of ageing or age-related diseases. PMID- 26373272 TI - Development of Next-Generation Immunomodulatory Antibodies for Cancer Therapy through Optimization of the IgG Framework. AB - In this issue of Cancer Cell, Dahan and colleagues demonstrate that the Fc region has a significant impact on the therapeutic capacity of checkpoint inhibitor antibodies targeting the PD-1/PD-L1 axis in pre-clinical tumor models. This work provides important insights with respect to the further clinical development of checkpoint inhibitors. PMID- 26373273 TI - The Amazing and Deadly Glioma Race. AB - In this issue of Cancer Cell, studies from Mazor and colleagues and Kim and colleagues use a combination of epigenetic and genetic approaches to reveal a complex evolutionary process underlying two of the biggest challenges facing neuro-oncology, specifically glioblastoma malignant progression and treatment resistance. PMID- 26373274 TI - Keeping It in the Family: ATRX Loss Promotes Persistent Sister Telomere Cohesion in ALT Cancer Cells. AB - In this issue of Cancer Cell, Ramamoorthy and Smith report that cancer cells that maintain their chromosome ends through alternative lengthening of telomeres (ALT) display persistent sister telomere cohesion. This delayed resolution of sister telomere cohesion depends upon the loss of ATRX and its histone-sequestering function and is associated with increased recombination between sister telomeres. PMID- 26373275 TI - Path Forward for RAF Therapies: Inhibition of Monomers and Dimers. AB - Current BRAF inhibitors block signaling from monomeric BRAF(V600E), but not from oncogenic RAS, which requires RAF dimerization. In this issue of Cancer Cell, Yao and colleagues investigate why current drugs are ineffective against RAF dimers, while Peng and colleagues describe a pan-RAF inhibitor targeting both monomeric and dimeric RAF. PMID- 26373276 TI - Engineering Anti-myeloma Responses Using Affinity-Enhanced TCR-Engineered T Cells. AB - NY-ESO-1 TCR-engineered T cells have shown activity in solid tumors. Recent work supports their use in multiple myeloma by showing that ex vivo antigen-specific expanded T cells traffic to and persist in bone marrow, are well tolerated, and produce promising response rates when infused after stem cell transplantation. PMID- 26373277 TI - FcgammaRs Modulate the Anti-tumor Activity of Antibodies Targeting the PD-1/PD-L1 Axis. AB - Immune checkpoint blockade of the programmed cell death protein 1 (PD-1) pathway by monoclonal antibodies (Abs) has shown promising clinical benefit in the treatment of multiple cancer types. We elucidated the contribution of the fragment crystallizable (Fc) domains of anti-PD-1 and anti-PD-ligand 1 (L1) Abs for their optimal anti-tumor activity. We revealed that distinct Fcgamma receptor (FcgammaRs) dependency and mechanisms account for the in vivo activity of anti-PD 1 versus anti-PD-L1 Abs. Anti-PD-1 Abs were found to be FcgammaR independent in vivo; the presence of FcgammaR-binding capacity compromises their anti-tumor activity. In contrast, the anti-PD-L1 Abs show augmented anti-tumor activity when activating FcgammaR binding is introduced into the molecules, altering myeloid subsets within the tumor microenvironment. PMID- 26373278 TI - DNA Methylation and Somatic Mutations Converge on the Cell Cycle and Define Similar Evolutionary Histories in Brain Tumors. AB - The evolutionary history of tumor cell populations can be reconstructed from patterns of genetic alterations. In contrast to stable genetic events, epigenetic states are reversible and sensitive to the microenvironment, prompting the question whether epigenetic information can similarly be used to discover tumor phylogeny. We examined the spatial and temporal dynamics of DNA methylation in a cohort of low-grade gliomas and their patient-matched recurrences. Genes transcriptionally upregulated through promoter hypomethylation during malignant progression to high-grade glioblastoma were enriched in cell cycle function, evolving in parallel with genetic alterations that deregulate the G1/S cell cycle checkpoint. Moreover, phyloepigenetic relationships robustly recapitulated phylogenetic patterns inferred from somatic mutations. These findings highlight widespread co-dependency of genetic and epigenetic events throughout brain tumor evolution. PMID- 26373279 TI - Spatiotemporal Evolution of the Primary Glioblastoma Genome. AB - Tumor recurrence following treatment is the major cause of mortality for glioblastoma multiforme (GBM) patients. Thus, insights on the evolutionary process at recurrence are critical for improved patient care. Here, we describe our genomic analyses of the initial and recurrent tumor specimens from each of 38 GBM patients. A substantial divergence in the landscape of driver alterations was associated with distant appearance of a recurrent tumor from the initial tumor, suggesting that the genomic profile of the initial tumor can mislead targeted therapies for the distally recurred tumor. In addition, in contrast to IDH1 mutated gliomas, IDH1-wild-type primary GBMs rarely developed hypermutation following temozolomide (TMZ) treatment, indicating low risk for TMZ-induced hypermutation for these tumors under the standard regimen. PMID- 26373280 TI - Frequent Derepression of the Mesenchymal Transcription Factor Gene FOXC1 in Acute Myeloid Leukemia. AB - Through in silico and other analyses, we identified FOXC1 as expressed in at least 20% of human AML cases, but not in normal hematopoietic populations. FOXC1 expression in AML was almost exclusively associated with expression of the HOXA/B locus. Functional experiments demonstrated that FOXC1 contributes to a block in monocyte/macrophage differentiation and enhances clonogenic potential. In in vivo analyses, FOXC1 collaborates with HOXA9 to accelerate significantly the onset of symptomatic leukemia. A FOXC1-repressed gene set identified in murine leukemia exhibited quantitative repression in human AML in accordance with FOXC1 expression, and FOXC1(high) human AML cases exhibited reduced morphologic monocytic differentiation and inferior survival. Thus, FOXC1 is frequently derepressed to functional effect in human AML. PMID- 26373281 TI - Loss of ATRX Suppresses Resolution of Telomere Cohesion to Control Recombination in ALT Cancer Cells. AB - The chromatin-remodeler ATRX is frequently lost in cancer cells that use ALT (alternative lengthening of telomeres) for telomere maintenance, but its function in telomere recombination is unknown. Here we show that loss of ATRX suppresses the timely resolution of sister telomere cohesion that normally occurs prior to mitosis. In the absence of ATRX, the histone variant macroH2A1.1 binds to the poly(ADP-ribose) polymerase tankyrase 1, preventing it from localizing to telomeres and resolving cohesion. The resulting persistent telomere cohesion promotes recombination between sister telomeres, while it suppresses inappropriate recombination between non-sisters. Forced resolution of sister telomere cohesion induces excessive recombination between non-homologs, genomic instability, and impaired cell growth, indicating the ATRX-macroH2A1.1-tankyrase axis as a potential therapeutic target in ALT tumors. PMID- 26373282 TI - Frontotemporal dementia-associated N279K tau mutant disrupts subcellular vesicle trafficking and induces cellular stress in iPSC-derived neural stem cells. AB - BACKGROUND: Pallido-ponto-nigral degeneration (PPND), a major subtype of frontotemporal dementia with parkinsonism related to chromosome 17 (FTDP-17), is a progressive and terminal neurodegenerative disease caused by c.837 T > G mutation in the MAPT gene encoding microtubule-associated protein tau (rs63750756; N279K). This MAPT mutation induces alternative splicing of exon 10, resulting in a modification of microtubule-binding region of tau. Although mutations in the MAPT gene have been linked to multiple tauopathies including Alzheimer's disease, frontotemporal dementia and progressive supranuclear palsy, knowledge regarding how tau N279K mutation causes PPND/FTDP-17 is limited. RESULTS: We investigated the underlying disease mechanism associated with the N279K tau mutation using PPND/FTDP-17 patient-derived induced pluripotent stem cells (iPSCs) and autopsy brains. In iPSC-derived neural stem cells (NSCs), the N279K tau mutation induced an increased ratio of 4-repeat to 3-repeat tau and accumulation of stress granules indicating elevated cellular stress. More significant, NSCs derived from patients with the N279K tau mutation displayed impaired endocytic trafficking as evidenced by accumulation of endosomes and exosomes, and a reduction of lysosomes. Since there were no significant differences in cellular stress and distribution of subcellular organelles between control and N279K skin fibroblasts, N279K-related vesicle trafficking defects are likely specific to the neuronal lineage. Consistently, the levels of intracellular/luminal vesicle and exosome marker flotillin-1 were significantly increased in frontal and temporal cortices of PPND/FTDP-17 patients with the N279K tau mutation, events that were not seen in the occipital cortex which is the most spared cortical region in the patients. CONCLUSION: Together, our results demonstrate that alterations of intracellular vesicle trafficking in NSCs/neurons likely contribute to neurodegeneration as an important disease mechanism underlying the N279K tau mutation in PPND/FTDP-17. PMID- 26373284 TI - Ultrasonic shears assistance can shorten the console time in robotic gastrectomy for early gastric cancer. AB - BACKGROUND: Robotic gastric surgery has been introduced and is being performed in many Japanese facilities. There are some limitations of devices capable to be used in the robotic arms in the da Vinci Surgical System. We have reviewed our first ten cases with early gastric cancer who underwent robot-assisted gastrectomy and have compared the operative time between cases who underwent the operation only with an electric cautery device and those in whom laparoscopic coagulating shears (LCS) through an assistant port were used. FINDINGS: We used an electric cautery device only in cases 1-3, and LCS in cases 4-10 except case 9. The mean operative time was 454 min in cases where only robotic devices were used and 414 min in those with LCS assist. The mean console time of 251 min in those with LCS assist was significantly shorter than that of 306 min in cases where only robotic devices were used. The number of dissected lymph nodes was satisfactory, and the estimated blood loss was small. Postoperative complications in two cases were slight and transient with short hospital stay. CONCLUSION: Assistant use of ultrasonic shears is useful to shorten the console time in robotic gastrectomy. PMID- 26373283 TI - Homonegativity, Religiosity, and the Intersecting Identities of Young Black Men Who Have Sex with Men. AB - Young, Black men who have sex with men (YBMSM) are disproportionately affected by HIV. Homonegativity, or the stigma associated with homosexuality, may be an important social factor influencing racial disparities in HIV. This research, conducted using an intersectional framework, examines experiences of homonegativity among YBMSM with a particular emphasis on the influence of the Black Church. We conducted 30 semi-structured interviews with YBMSM ages 16-24. Interview transcripts were analyzed in MAXQDA using thematic content analysis, guided by principles of grounded theory and constant comparative method. The Black Church is an integral aspect of YBMSM's identity, history, family, and community life. As such, the Church's construction of homosexuality dominated throughout YBMSM's lives. The expectations of masculinity facing YBMSM emphasize expectations of physical and sexual dominance, which are viewed as incompatible with homosexuality. Participants describe complex decision-making around whether to disclose their sexuality and to whom, and weigh the consequences of disclosure and non-disclosure. For many YBMSM, their multiple, intersecting identities significantly influenced their experiences with homonegativity and their decisions about disclosing their sexual orientation. Findings lend support for the need to develop community-, family-, and church-based stigma reduction interventions that address homonegativity among YBMSM. PMID- 26373285 TI - The hnRNP A1 homolog Hrb87F/Hrp36 is important for telomere maintenance in Drosophila melanogaster. AB - Unlike the telomerase-dependent mammalian telomeres, HeT-A, TART, and TAHRE (HTT) retroposon arrays regulate Drosophila telomere length. Cap prevents telomeric associations (TAs) and telomeric fusions (TFs). Our results suggest important roles of Hrb87F in telomeric HTT array and cap maintenance in Drosophila. All chromosome arms, except 2L, in Df(3R)Hrb87F homozygotes (Hrb87F-null) displayed significantly elongated telomeres with amplified HTT arrays and high TAs, all of which resolved without damage. Presence of FLAG-tagged Hrb87F (FLAG-Hrb87F) on cap and subtelomeric regions following hsFLAG-Hrb87F transgene expression in Df(3R)Hrb87F homozygotes suppressed TAs without affecting telomere length. A normal X-chromosome telomere expanded within five generations in Hrb87F-null background and displayed high TAs, but not when hsFLAG-Hrb87F was co-expressed. Tel (1) /Gaiano line or HP1 loss-of-function mutant-derived expanded telomeres carry Hrb87F on cap and HTT arrays while Hrb87F-null telomeres have HP1 and HOAP on caps and expanded HTT arrays. ISWI, seen only on cap on normal telomeres, was abundant on Hrb87F-null expanded HTT arrays. Extended telomeres derived from Tel (1) (Gaiano) or HP1-null mutation background interact with those from Hrb87F null, since while the end association frequency was negligible in Df(3R)Hrb87F/+ nuclei, it increased significantly in co-presence of Tel (1) or HP1-null-based expanded telomere/s. Together, these suggest complex interactions between members of the proteome of telomere so that absence of any key member leads to telomere expansion and/or enhanced TAs/TFs. HTT expansion in Hrb87F-null condition is not developmental but a germline event presumably because absence of Hrb87F in germline may deregulate HTT retroposition/replication leading to telomere elongation. PMID- 26373286 TI - The synergistic effect of density stress during the maternal period and adulthood on immune traits of root vole (Microtus oeconomus) individuals-a field experiment. AB - The literature reveals that stress in early life or adulthood can influence immune function. As most studies on this are from the laboratory, there is a need for replicated studies in wild animals. This study aims to examine the effects of density stress during the maternal period and adulthood on immune traits of root vole (Microtus oeconomus) individuals. Four replicated high- and low-density parental populations were established, from which we obtained offspring and assigned each into four enclosures, two for each of the two density treatments used in establishing parental populations. The F1 offspring fecal corticosterone metabolite response to acute immobilization stress, anti-keyhole limpet hemocyanin immunoglobulin G (anti-KLH IgG) level, phytohemagglutinin (PHA) delayed hypersensitivity and hematology at the end of the first breeding season, and prevalence and intensity of coccidial infection throughout the two breeding seasons, were tested. Density-induced maternally stressed offspring had delayed responses to acute immobilization stress. Density-stressed offspring as adults had reduced anti-KLH IgG levels and PHA responses, and the effects further deteriorated in maternally stressed offspring, leading to higher coccidial infection in the first breeding season than in the second. No correlations were found between immune traits or coccidial infection and survival over winter. These findings indicated that the combined density stresses during the maternal period and adulthood exhibited negative synergistic effects on immune traits. The synergistic effects lead to higher coccidial infection; however, this consequently reduced the risk of subsequent infection. The increased coccidial infection mediated by the synergistic effects may have an adaptive value in the context of the environment. PMID- 26373287 TI - Hyperkalemic cardiac arrhythmia resulting from short-term ingestion of potassium citrate for the management of ureter stones. PMID- 26373288 TI - Mitogen-activated protein kinase activator with WD40 repeats (MAWD) and MAWD binding protein induce cell differentiation in gastric cancer. AB - BACKGROUND: Our previous proteomic analysis revealed that mitogen-activated protein kinase activator with WD40 repeats (MAWD) and MAWD-binding protein (MAWBP) were downregulated in gastric cancer (GC) tissues. These proteins interacted and formed complexes in GC cells. To investigate the role of MAWD and MAWBP in GC differentiation, we analyzed the relationship between MAWD/MAWBP and clinicopathologic characteristics of GC tissues and examined the expression of E cadherin and pepsinogen C (PGC)-used as gastric mucosa differentiation markers-in MAWD/MAWBP-overexpressing GC cells and xenografts. METHODS: We measured MAWD, MAWBP, transforming growth factor-beta (TGF-beta), E-cadherin, and PGC expression in 223 GC tissues and matched-adjacent normal tissues using tissue microarray and immunohistochemistry (IHC) analyses, and correlated these expression levels with clinicopathologic features. MAWD and MAWBP were overexpressed alone or together in SGC7901 cells and then E-cadherin, N-cadherin, PGC, Snail, and p-Smad2 levels were determined using western blotting, semiquantitative RT-PCR, and immunofluorescence analysis. Alkaline phosphatase (AKP) activity was measured to investigate the differentiation level of various transfected cells, and the transfected cells were used in tumorigenicity assays and for IHC analysis of protein expression in xenografts. RESULTS: MAWD/MAWBP positive staining was significantly lower in GC tissues than in normal samples (P < 0.001), and the expression of these proteins was closely correlated with GC differentiation grade. Kaplan-Meier survival curves indicated that low MAWD and MAWBP expression was associated with poor patient survival (P < 0.05). The differentiation-related proteins E-cadherin and PGC were expressed in GC tissues at a lower level than in normal tissues (P < 0.001), but were upregulated in MAWD/MAWBP-overexpressing cells. N-cadherin and Snail expression was strongr in vector-expressing cells and comparatively weaker in MAWD/MAWBP co-overexpressing cells. MAWD/MAWBP co overexpression inhibited Smad2 phosphorylation and nuclear translocation (P < 0.05), and AKP activity was lowest in MAWD/MAWBP coexpressing cells and highest in vector-expressing cells (P < 0.001). TGF-beta, E-cadherin, and PGC expression in xenograft tumors derived from MAWD/MAWBP coexpressing cells was higher than that in control. CONCLUSIONS: MAWD and MAWBP were downregulated and associated with the differentiation grade in GC tissues. MAWD and MAWBP might induce the expression of differentiation-related proteins by modulating TGF-beta signaling in GC cells. PMID- 26373289 TI - Poor peer relations predict parent- and self-reported behavioral and emotional problems of adolescents with gender dysphoria: a cross-national, cross-clinic comparative analysis. AB - This study is the third in a series to examine behavioral and emotional problems in children and adolescents with gender dysphoria in a comparative analysis between two clinics in Toronto, Ontario, Canada and Amsterdam, the Netherlands. In the present study, we report Child Behavior Checklist (CBCL) and Youth Self Report (YSR) data on adolescents assessed in the Toronto clinic (n = 177) and the Amsterdam clinic (n = 139). On the CBCL and the YSR, we found that the percentage of adolescents with clinical range behavioral and emotional problems was higher when compared to the non-referred standardization samples but similar to the referred adolescents. On both the CBCL and the YSR, the Toronto adolescents had a significantly higher Total Problem score than the Amsterdam adolescents. Like our earlier studies of CBCL data of children and Teacher's Report Form data of children and adolescents, a measure of poor peer relations was the strongest predictor of CBCL and YSR behavioral and emotional problems in gender dysphoric adolescents. PMID- 26373290 TI - Chronic Systemic Immune Dysfunction in African-Americans with Small Vessel-Type Ischemic Stroke. AB - The incidence of small vessel-type (lacunar) ischemic strokes is greater in African-Americans compared to whites. The chronic inflammatory changes that result from lacunar stroke are poorly understood. To elucidate these changes, we measured serum inflammatory and thrombotic biomarkers in African-Americans at least 6 weeks post-stroke compared to control individuals. Cases were African Americans with lacunar stroke (n = 30), and controls were age-matched African Americans with no history of stroke or other major neurologic disease (n = 37). Blood was obtained >6 weeks post-stroke and was analyzed for inflammatory biomarkers. Freshly isolated peripheral blood mononuclear cells were stimulated with lipopolysaccharide (LPS) to assess immune responsiveness in a subset of cases (n = 5) and controls (n = 4). After adjustment for covariates, the pro inflammatory biomarkers, soluble vascular cadherin adhesion molecule-1 (sVCAM-1) and thrombin anti-thrombin (TAT), were independently associated with lacunar stroke. Immune responsiveness to LPS challenge was abnormal in cases compared to controls. African-Americans with lacunar stroke had elevated blood levels of VCAM 1 and TAT and an abnormal response to acute immune challenge >6 weeks post stroke, suggesting a chronically compromised systemic inflammatory response. PMID- 26373291 TI - Who is eligible for randomized trials? A comparison between the exclusion criteria defined by the ISCHEMIA trial and 3102 real-world patients with stable coronary artery disease undergoing stent implantation in a single cardiology center. AB - BACKGROUND: Randomized controlled trials are the gold standard for evaluating therapy; however, controversy exists regarding the applicability of such results to daily practice, as patients are often pre-selected and may not reflect real world clinical settings. We studied the eligibility criteria for 3102 "real-life" patients with stable coronary artery disease (SCAD) according to the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial exclusion criteria. The aim of our analysis was to estimate the percentage of real-life patients who would have met the exclusion criteria for the ISCHEMIA trial. METHODS: We analyzed 3102 patients with SCAD referred to the Silesian Center for Heart Disease who underwent both coronary angiography and stent implantation between January 2006 and December 2011. The patients were divided into two groups. Group A was composed of patients with SCAD who would have been excluded from the ongoing ISCHEMIA trial, whereas group B represented the remaining patients. RESULTS: A total of 1900 (61.3%) patients met at least one of the exclusion criteria. The most frequent exclusion criterion noted was revascularization within the previous 12 months (938 patients; 49.4%), followed by unacceptable level of angina symptoms (532 patients; 28 %), low ejection fraction (467 patients; 24.6%), and acute coronary syndrome within the previous 2 months (456 patients; 24%). Patients from our cohort who would have been excluded from the ISCHEMIA trial were older, had more comorbidities, and experienced worse long-term outcomes. CONCLUSIONS: The ISCHEMIA trial exclusion criteria ruled out the majority of the patients with SCAD undergoing percutaneous coronary intervention in "real life". Our cohort of patients who would have been excluded from the ISCHEMIA trial had more comorbidities and experienced significantly worse long-term outcomes than patients who did not meet the ISCHEMIA trial exclusion criteria. TRIAL REGISTRATION: ClinicalTrials.gov NCT01471522. PMID- 26373292 TI - Hypnocyclicus thermotrophus gen. nov., sp. nov. isolated from a microbial mat in a hydrothermal vent field. AB - The bacterial strain, IR-2T, was isolated from a microbial mat sampled near a hydrothermal vent in the Greenland Sea. Phylogenetic analysis, based on the 16S rRNA gene, showed that the closest relatives of IR-2T were Ilyobacter tartaricus, Ilyobacter insuetus, Propionigenium modestum and Fusobacterium varium (91 % 16S rRNA gene sequence similarity). The cells of the novel strain were Gram-stain negative and pleomorphic; changing from long motile rods to non-motile ring structures during the growth cycle. Growth occurred at 20-55 degrees C (optimally at 48 degrees C), with 1-6 % (w/v) NaCl (optimally with 2 %), and at pH 5.3-8.0 (optimally at pH 6.0-8.0). The strain had obligate fermentative growth on various sugars and yeast extract. The DNA G+C content of strain IR-2T was 25.7 mol%. The cell sugars comprised mainly ribose, mannose and glucose, while the main polar lipids were glycolipids, phospholipids, phosphatidylglycerol and diphosphatidylglycerol. The fatty acid content of strain IR-2 was dominated by saturated and unsaturated iso-branched or anteiso-branched forms. Strain IR-2 represents a novel genus and species, for which the name Hypnocyclicus thermotrophus gen. nov., sp. nov. is proposed. The type strain is IR-2T ( = DSM 100055 = JCM 30901). PMID- 26373293 TI - Rapid Identification of Methicillin-Resistant Staphylococcus aureus (MRSA) by the Vitek MS Saramis system. AB - A rapid, sensitive, and accurate Vitek MS assay was developed to distinguish clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) from clinical isolates of methicillin-sensitive Staphylococcus aureus (MSSA) by developing an in-house knowledgebase of SuperSpectra. Three unique peaks, including peaks at 2305.6 and 3007.3 Da specific to MRSA, and 6816.7 Da specific to MSSA, were selected for differentiating MRSA and MSSA. This assay accurately identified 84 and 91% of clinical MRSA and MSSA strains out of the total 142 clinically acquired S. aureus strains that were tested. This method will greatly improve the efficiency of single clinical sample identification of MRSA, thereby facilitating a reduction in the transmission of MRSA in clinical settings. PMID- 26373295 TI - [Chemical peel treatments in dermatology]. AB - Chemical peel treatments, which utilize a number of chemical peeling solutions subject to patient indication, are an easy to learn therapeutic technique suited for, in particular, various types of acne, acne scars, actinic keratosis and "sun damaged skin". Especially the positive and long-lasting results of deep peels in the area of skin rejuvenation are deemed the gold standard against which other techniques, including lasers, must compare themselves. Other benefits of chemical peels include the flexibility to mix and match chemical solutions to custom design the treatment best suited for the desired degree of skin penetration, as well as the relatively low cost. PMID- 26373296 TI - Evaluation of the good tumor response of embryonal tumor with abundant neuropil and true rosettes (ETANTR). AB - The embryonal tumor with abundant neuropil and true rosettes is a rare and highly malignant variant of embryonal brain tumors. It usually affects infants and young children under the age of 4 years and exhibits a very aggressive course with a dismal prognosis. For the 68 cases reported to date the mean age at diagnosis was 25.42 months (range 3-57 months). Survival data are available for 48 children (including our case): the median overall survival is 13.0 months, though 6 (9%) of the children have had a relative long survival (>30 months). The aggressive combined treatment, involving primary surgical tumor removal, adjuvant polychemotherapy, including high-dose chemotherapy with stem cell transplantation, radiotherapy and radiochemotherapy, might play an important role in the longer survival. We have performed a literature review and we present here a multimodal-treated case of a 2- year-old girl with a long survival, who was reoperated when recurrence occurred. The residual tumor demonstrated a good response to temozolomide radiochemotherapy (craniospinal axis + boost) and followed by maintenance temozolomide. The described complex aggressive treatment option might be considered for future cases of this tumor entity. PMID- 26373297 TI - Outcome of gamma knife radiosurgery for metastatic brain tumors derived from non small cell lung cancer. AB - The purpose of this study was to analyze outcomes in patients treated with gamma knife radiosurgery (GKS) for brain metastases from non-small cell lung cancer (NSCLC). We retrospectively reviewed the medical records of 817 patients who underwent GKS for brain metastases from NSCLC between January 2002 and December 2012. A total of 1363 GKS procedures were performed for 2970 lesions. The median overall survival time from the initial GKS was 13 months and the salvage treatment-free survival from the first GKS was 6.5 months. Younger age (<=65 years), female sex, better RPA class, higher DS-GPA score, adenocarcinoma, synchronous onset, and lower integrated value of the "numbers and cumulative volume of tumors" were associated with better outcomes. Among the 601 patients with an available follow up image, the pattern of the first progression after initial GKS was the development of new lesions in 356 patients (59.2 %), regrowth of treated lesions in 106 patients (17.6 %), and leptomeningeal seeding (LMS) in 51 patients (8.5 %). Among the deceased, the last MRI performed prior to death was evaluated in 409 patients and showed progression in 263 patients (64.3 %), despite multiple salvage treatments. LMS was identified in 63 patients (15.4 %); a rate much higher than the incidence at first progression. Intracranial tumor burden, defined as the integrated value of the "number of the lesions and cumulative tumor volume", is a new prognostic factor of greater significance than tumor volume or number alone when analyzed as separate factors. Although the cause of death was not progression of brain lesions in the majority of patients, the brain lesions tended to have been persistently progressive in most patients, despite repeated salvage treatment. LMS is an important pattern of treatment failure, in addition to local progression or development of new lesions, particularly in the terminal phase of the disease. PMID- 26373298 TI - A systematic review of social, economic and diplomatic aspects of short-term medical missions. AB - BACKGROUND: Short-term medical missions (STMMs) represent a grass-roots form of aid, transferring medical services rather than funds or equipment. The objective of this paper is to review empirical studies on social, economic and diplomatic aspects of STMMs. METHODS: A systematic literature review was conducted by searching PubMed and EBSCOhost for articles published from 1947-2014 about medical missions to lower and middle income countries (LMICs). Publications focused on military, disaster and dental service trips were excluded. A data extraction process was used to identify publications relevant to our objective stated above. RESULTS: PubMed and EBSCOhost searches provided 4138 and 3262 articles respectively for review. Most articles that provide useful information have appeared in the current millennium and are found in focused surgical journals. Little attention is paid to aspects of volunteerism, altruism and philanthropy related to STMM activity in the literature reviewed (1 article). Evidence of professionalization remains scarce, although elements including guidelines and tactical instructions have been emerging (27 articles). Information on costs (10 articles) and commentary on the relevance of market forces (1 article) are limited. Analyses of spill-over effects, i.e., changing attitudes of physicians or their communities towards aid, and characterizations of STMMs as meaningful foreign aid or strategic diplomacy are few (4 articles). CONCLUSIONS: The literature on key social, economic and diplomatic aspects of STMMs and their consequences is sparse. Guidelines, tactical instructions and attempts at outcome measures are emerging that may better professionalize the otherwise unregulated activity. A broader discussion of these key aspects may lead to improved accountability and intercultural professionalism to accompany medical professionalism in STMM activity. PMID- 26373300 TI - The Frequency of White Blood Cell and Temperature Events During Mechanical Ventilation and Their Association With Ventilator-Associated Events. AB - BACKGROUND: Changes in white blood cell (WBC) counts and/or temperature could have important implications in patients on ventilators, but the frequency of these events is uncertain. METHODS: We reviewed the medical records from 281 ventilation episodes in our medical intensive care unit to determine patient characteristics and the indications for ventilation. We determined the number of days during each ventilation episode in which the temperature (<96.8 degrees F, >100.4 degrees F) or WBC count (<4000/uL, >12 000/uL) was out of the normal range. RESULTS: This study included 257 patients with a mean Acute Physiology and Chronic Health Evaluation 2 score of 13.5 +/- 5.9 and a mean initial Pao2/Fio2 of 210 +/- 110. The median number of ventilator days was 4 (interquartile range, 3 9). One hundred ninety-six of 275 eligible ventilator episodes (71.3%) had 1 or more temperature events, and 194 of 253 eligible ventilator episodes (76.7%) had 1 or more WBC events. Nineteen patients met the Center for Disease Control criteria for a ventilator-associated event (VAE). Twelve patients had an increased WBC count during the VAE period, and 11 had an increased temperature during this period. CONCLUSIONS: White blood cell counts and temperature events occur frequently in patients on ventilators and need evaluation but do not reliably identify patients with ventilator-associated complications. PMID- 26373299 TI - Inhibition of Survival Pathways MAPK and NF-kB Triggers Apoptosis in Pancreatic Ductal Adenocarcinoma Cells via Suppression of Autophagy. AB - BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with a survival rate of 4-6 months from diagnosis. PDAC is the fourth leading cause of cancer-related death in the Western world, with a mortality rate of 10 cases per 100,000 population. Chemotherapy constitutes only a palliative strategy, with limited effects on life expectancy. AIMS: To investigate the biological response of PDAC to mitogen-activated protein kinase (MAPK) and NF-kappaB (NF-kB) inhibitors and the role of autophagy in the modulation of these signaling pathways in order to address the challenge of developing improved medical protocols for patients with PDAC. METHODS: Two ATCC cell lines, MIAPaCa-2 and PANC-1, were used as PDAC models. Cells were exposed to inhibitors of MAPK or NF kB survival pathways alone or after autophagy inhibition. Several aspects were analyzed, as follows: cell proliferation, by [(3)H]TdR incorporation; cell death, by TUNEL assay, regulation of autophagy by LC3-II expression level and modulation of pro-and anti-apoptotic proteins by Western blot. RESULTS: We demonstrated that the inhibition of the MAPK and NF-kB survival pathways with U0126 and caffeic acid phenethyl ester (CAPE), respectively, produced strong inhibition of pancreatic tumor cell growth without inducing apoptotic death. Interestingly, U0126 and CAPE induced apoptosis after autophagy inhibition in a caspase dependent manner in MIA PaCa-2 cells and in a caspase-independent manner in PANC 1 cells. CONCLUSIONS: Here we present evidence that allows us to consider a combined therapy regimen comprising an autophagy inhibitor and a MAPK or NF-kB pathway inhibitor as a possible treatment strategy for pancreatic cancer. PMID- 26373302 TI - Heavy metal pollution and ecological risk assessment of the paddy soils near a zinc-lead mining area in Hunan. AB - Soil pollution by Cd, Hg, As, Pb, Cr, Cu, and Zn was characterized in the area of the mining and smelting of metal ores at Guiyang, northeast of Hunan Province. A total of 150 topsoil (0-20 cm) samples were collected in May 2012 with a nominal density of one sample per 4 km(2). High concentrations of heavy metals especially, Cd, Zn, and Pb were found in many of the samples taken from surrounding paddy soil, indicating a certain extent of spreading of heavy metal pollution. Sequential extraction technique and risk assessment code (RAC) were used to study the mobility of chemical forms of heavy metals in the soils and their ecological risk. The results reveal that Cd represents a high ecological risk due to its highest percentage of the exchangeable and carbonate fractions. The metals of Zn and Cu pose a medium risk, and the rest of the metals represent a low environmental risk. The range of the potential ecological risk of soil calculated by risk index (RI) was 123.5~2791.2 and revealed a considerable-high ecological risk in study area especially in the neighboring and surrounding the mining activities area. Additionally, cluster analyses suggested that metals such as Pb, As, Hg, Zn, and Cd could be from the same sources probably related to the acidic drainage and wind transport of dust. Cluster analysis also clearly distinguishes the samples with similar characteristics according to their spatial distribution. The results could be used during the ecological risk screening stage, in conjunction with total concentrations and metal fractionation values to better estimate ecological risk. PMID- 26373303 TI - Treatment of real wastewater produced from Mobil car wash station using electrocoagulation technique. AB - This paper deals with the electrocoagulation of real wastewater produced from a car wash station using a new cell design featuring a horizontal spiral anode placed above a horizontal disc cathode. The study dealt with the chemical oxygen demand (COD) reduction and turbidity removal using electrodes in a batch mode. Various operating parameters such as current density, initial pH, NaCl concentration, temperature, and electrode material were examined to optimize the performance of the process. Also, characterization of sludge formed during electrocoagulation was carried out. The results indicated that the COD reduction and turbidity removal increase with increasing the current density and NaCl concentration; pH from 7 to 8 was found to be optimum for treating the wastewater. Temperature was found to have an insignificant effect on the process. Aluminum was superior to iron as a sacrificial electrode material in treating car wash wastewater. Energy consumption based on COD reduction ranged from 2.32 to 15.1 kWh/kg COD removed depending on the operating conditions. Finally, the sludge produced during electrocoagulation using aluminum electrodes was characterized by scanning electron microscopy (SEM) and energy dispersive spectrometry (EDS) analysis. PMID- 26373304 TI - Detection and prediction of land cover changes using Markov chain model in semi arid rangeland in western Iran. AB - The study of changes and destruction rate in the previous years as well as the possibility of prediction of these changes in the following years has a key role in optimal planning, controlling, and restricting non-normative changes in the future. This research was approached to detecting land use/cover changes (1985 2007) and to forecast the changes in the future (2021) use of multitemporal satellite imagery in semi-arid area in western Iran. A supervised classification of multilayer perceptron (MLP) was applied for detecting land use changes. The study area was classified into five classes, those of forest, rangeland, agriculture, residential, and barren lands. The change detection analysis indicated a decreasing trend in forest cover by 30.42%, while other land uses were increased during 1985 to 2007. The land use changes were predicted using Markov chain model for 2021. The model was calibrated by comparing the simulated map with the real detected classes of land cover in 2007. Then, for further model processing, an acceptable accuracy at 83% was achieved between them. Finally, land use changes were predicted by using transition matrix derived from calibrated approach. The findings of this study demonstrate a rapid change in land use/cover for the coming years. Transforming the forest into other land uses especially rangeland and cropland is the main land cover changes in the future. Therefore, the planning of protection and restoration of forest cover should be an essential program for decision-makers in the study area. PMID- 26373305 TI - Molecular characterisation of Bacillus chitinase for bioconversion of chitin waste. AB - In this work chitin was extracted chemically from shrimp shells. Seventeen Bacillus isolates were screened for chitinolytic activity. The chitinolytic strains of Bt. were screened at different temperatures and pHs for their hydrolytic potentials. By using a pair of specific primers, endochitinase gene was amplified from SBS Bt-5 strain through PCR, and then cloned into pTZ57 TA cloning vector and transferred in Escherichia coli DH5alpha strain. The sequenced gene (GenBank Accession No: HE995800) consists of 2031 nucleotides capable of encoding 676 residues. The protein consisted of three functional domains with a calculated molecular mass of 74.53 kDa and a pI value of 5.83. The amino acid sequence of chi gene showed 99% similarity to the genes of Bt MR11 endochitinase, Bt serovar kurstaki chitinase (kchi), Bt strain MR21 endochitinase and Bacillus cereus B4264. PMID- 26373306 TI - Critical role of PPARgamma in water balance. PMID- 26373308 TI - Hybrid-Lambda: simulation of multiple merger and Kingman gene genealogies in species networks and species trees. AB - BACKGROUND: There has been increasing interest in coalescent models which admit multiple mergers of ancestral lineages; and to model hybridization and coalescence simultaneously. RESULTS: Hybrid-Lambda is a software package that simulates gene genealogies under multiple merger and Kingman's coalescent processes within species networks or species trees. Hybrid-Lambda allows different coalescent processes to be specified for different populations, and allows for time to be converted between generations and coalescent units, by specifying a population size for each population. In addition, Hybrid-Lambda can generate simulated datasets, assuming the infinitely many sites mutation model, and compute the F ST statistic. As an illustration, we apply Hybrid-Lambda to infer the time of subdivision of certain marine invertebrates under different coalescent processes. CONCLUSIONS: Hybrid-Lambda makes it possible to investigate biogeographic concordance among high fecundity species exhibiting skewed offspring distribution. PMID- 26373309 TI - Two iron-regulated transporter (IRT) genes showed differential expression in poplar trees under iron or zinc deficiency. AB - Two iron-regulated transporter (IRT) genes were cloned from the iron chlorosis resistant (PtG) and susceptible (PtY) Populus tremula 'Erecta' lines. Nucleotide sequence analysis showed no significant difference between PtG and PtY. The predicted proteins contain a conserved ZIP domain with 8 transmembrane (TM) regions. A ZIP signature sequence was found in the fourth TM domain. Phylogenetic analysis revealed that PtIRT1 was clustered with tomato and tobacco IRT genes that are highly responsible to iron deficiency. The PtIRT3 gene was clustered with the AtIRT3 gene that was related to zinc and iron transport in plants. Tissue specific expression indicated that PtIRT1 only expressed in the root, while PtIRT3 constitutively expressed in all tested tissues. Under iron deficiency, the expression of PtIRT1 was dramatically increased and a significantly higher transcript level was detected in PtG than in PtY. Iron deficiency also enhanced the expression of PtIRT3 in PtG. On the other hand, zinc deficiency down-regulated the expression of PtIRT1 and PtIRT3 in both PtG and PtY. Zinc accumulated significantly under iron-deficient conditions, whereas the zinc deficiency showed no significant effect on iron accumulation. A yeast complementation test revealed that the PtIRT1 and PtIRT3 genes could restore the iron uptake ability under the iron uptake-deficiency condition. The results will help understand the mechanisms of iron deficiency response in poplar trees and other woody species. PMID- 26373310 TI - Fe-, Co-, and Ni-Loaded Porous Activated Carbon Balls as Lightweight Microwave Absorbents. AB - Porous activated carbon ball (PACB) composites impregnated with iron, cobalt, nickel and/or their oxides were synthesized through a wet chemistry method involving PACBs as the carrier to load Fe(3+), Co(2+), and Ni(2+) ions and a subsequent carbothermal reduction at different annealing temperatures. The results show that the pyrolysis products of nitrates and/or the products from the carbothermal reduction are embedded in the pores of the PACBs, with different distributions, resulting in different crystalline phases. The as-prepared PACB composites possessed high specific surface areas of 791.2-901.5 m(2) g(-1) and low densities of 1.1-1.3 g cm(-3). Minimum reflection loss (RL) values of -50.1, 20.6, and -20.4 dB were achieved for Fe-PACB (annealed at 500 degrees C), Co PACB (annealed at 800 degrees C), and Ni-PACB (annealed at 800 degrees C) composites, respectively. Moreover, the influence of the amount of the magnetic components in the PACB composites on the microwave-absorbing performances was investigated, further confirming that the dielectric loss was the primary contributor to microwave absorption. PMID- 26373311 TI - Global summary of maternal and newborn vitamin D status - a systematic review. AB - Pregnant women and newborns are at increased risk of vitamin D deficiency. Our objective was to create a global summary of maternal and newborn vitamin D status. We completed a systematic review (1959-2014) and meta-analysis of studies reporting serum 25-hydroxyvitamin D [25(OH)D] concentration in maternal and newborn populations. The 95 identified studies were unevenly distributed by World Health Organization (WHO) region: Americas (24), European (33), Eastern Mediterranean (13), South-East Asian (7), Western Pacific (16) and African (2). Average maternal 25(OH)D concentrations (nmol L(-1) ) by region were 47-65 (Americas), 15-72 (European), 13-60 (Eastern Mediterranean), 20-52 (South-East Asian), 42-72 (Western Pacific) and 92 (African). Average newborn 25(OH)D concentrations (nmol L(-1) ) were 35-77 (Americas), 20-50 (European), 5-50 (Eastern Mediterranean), 20-22 (South-East Asian), 32-67 (Western Pacific) and 27 35 (African). The prevalences of 25(OH)D <50 and <25 nmol L(-1) by WHO region in pregnant women were: Americas (64%, 9%), European (57%, 23%), Eastern Mediterranean (46%, 79%), South-East Asian (87%, not available) and Western Pacific (83%, 13%). Among newborns these values were: Americas (30%, 14%), European (73%, 39%), Eastern Mediterranean (60%, not available), South-East Asian (96%, 45%) and Western Pacific (54%, 14%). By global region, average 25(OH)D concentration varies threefold in pregnant women and newborns, and prevalence of 25(OH)D <25 nmol L(-1) varies eightfold in pregnant women and threefold in newborns. Maternal and newborn 25(OH)D concentrations are highly correlated. Addressing vitamin D deficiency in pregnant women and newborns should be a global priority. To protect children from the adverse effects of vitamin D deficiency requires appropriate interventions during both pregnancy and childhood. PMID- 26373313 TI - EHS Testing of Products Containing Nanomaterials: What is Nano Release? PMID- 26373312 TI - Association between tumour necrosis-alpha gene polymorphisms and acne vulgaris in a Pakistani population. AB - BACKGROUND: The cytokine tumour necrosis factor (TNF)-alpha is a well-studied potent candidate mediator that is systemically involved in a variety of inflammatory diseases. Several single nucleotide polymorphisms (SNPs) of the TNF alpha gene have been studied with regard the pathogenesis of acne vulgaris, but the results have been inconclusive. AIM: This case-control study investigated the association of the TNF -308 G>A and -238 G>A SNPs with acne vulgaris in a high risk Pakistani population. METHODS: In total, 160 healthy controls and 140 patients with acne were enrolled in this study. Polymorphisms were determined by PCR and restriction fragment length polymorphism analysis. RESULTS: Our data showed that the TNF -308 G>A and TNF -238 G>A SNPs were present at a significantly higher rate in cases than in controls (P < 0.01 and P < 0.02; respectively). There was a significant difference between the G and A alleles from patients with acne and controls for -308 G>A (OR = 1.5, 95% CI = 1.07-2.19, P < 0.02) and -238 G>A (OR=1.6, 95% CI = 1.06-2.44, P = 0.02) genotype. Moreover, the severity of acne was significantly associated with TNF genotype (TNF -308 G>A: chi2 = 34.6, P < 0.001; TNF -238 G>AL chi2 = 12.9, P < 0.01). CONCLUSION: Our data suggest that the TNF -308 G>A and TNF -238 G>A SNPs may contribute to the pathogenesis of acne in the study population. Furthermore, patients with severe acne showed an increased frequency of mutant TNF genotypes at -308 and 238 compared with patients with less severe acne. PMID- 26373314 TI - Alternative Hfq-sRNA interaction modes dictate alternative mRNA recognition. AB - Many bacteria use small RNAs (sRNAs) and the RNA chaperone Hfq to regulate mRNA stability and translation. Hfq, a ring-shaped homohexamer, has multiple faces that can bind both sRNAs and their mRNA targets. We find that Hfq has at least two distinct ways in which it interacts with sRNAs; these different binding properties have strong effects on the stability of the sRNA in vivo and the sequence requirements of regulated mRNAs. Class I sRNAs depend on proximal and rim Hfq sites for stability and turn over rapidly. Class II sRNAs are more stable and depend on the proximal and distal Hfq sites for stabilization. Using deletions and chimeras, we find that while Class I sRNAs regulate mRNA targets with previously defined ARN repeats, Class II sRNAs regulate mRNAs carrying UA rich rim-binding sites. We discuss how these different binding modes may correlate with different roles in the cell, with Class I sRNAs acting as emergency responders and Class II sRNAs acting as silencers. PMID- 26373315 TI - alpha-Synuclein oligomers pump it up! PMID- 26373316 TI - Infective Endocarditis in Adults: Diagnosis, Antimicrobial Therapy, and Management of Complications: A Scientific Statement for Healthcare Professionals From the American Heart Association. AB - BACKGROUND: Infective endocarditis is a potentially lethal disease that has undergone major changes in both host and pathogen. The epidemiology of infective endocarditis has become more complex with today's myriad healthcare-associated factors that predispose to infection. Moreover, changes in pathogen prevalence, in particular a more common staphylococcal origin, have affected outcomes, which have not improved despite medical and surgical advances. METHODS AND RESULTS: This statement updates the 2005 iteration, both of which were developed by the American Heart Association under the auspices of the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease of the Young. It includes an evidence-based system for diagnostic and treatment recommendations used by the American College of Cardiology and the American Heart Association for treatment recommendations. CONCLUSIONS: Infective endocarditis is a complex disease, and patients with this disease generally require management by a team of physicians and allied health providers with a variety of areas of expertise. The recommendations provided in this document are intended to assist in the management of this uncommon but potentially deadly infection. The clinical variability and complexity in infective endocarditis, however, dictate that these recommendations be used to support and not supplant decisions in individual patient management. PMID- 26373317 TI - Infective Endocarditis in Childhood: 2015 Update: A Scientific Statement From the American Heart Association. PMID- 26373318 TI - Safety, efficacy and prognostic analyses of sunitinib in the post-marketing surveillance study of Japanese patients with gastrointestinal stromal tumor. AB - OBJECTIVE: This study was conducted to expand the sunitinib safety database in Japanese imatinib-resistant/-intolerant gastrointestinal stromal tumor patients. Retrospective analyses investigated common adverse events as potential prognostic markers. METHODS: Four hundred and seventy patients who received sunitinib between June 2008 and November 2009 were analyzed for safety, progression-free survival and overall survival; 386 for objective response rate; 88% received sunitinib on Schedule 4/2 starting at 50 mg/day. RESULTS: No unexpected safety issues occurred. Grade >= 3 adverse events occurred in 70%, most commonly thrombocytopenia (33%), neutropenia (22%) and leukopenia (15%). Objective response rate was 20% (95% confidence interval 16-24). Median progression-free survival was 22.4 weeks (95% confidence interval, 21.7-24.0). The overall survival rate at 24 weeks was 91% (95% confidence interval, 88-94). Higher relative dose intensity (>=70 vs. <70%) during the first 6 weeks and better Eastern Cooperative Oncology Group performance status (0 vs. >=1) were associated with longer progression-free survival (24.0 vs. 20.1 weeks; P = 0.011; and 24.1 vs. 16.9 weeks; P < 0.001) and higher 24-week overall survival rate (94 vs. 83%; P < 0.001; and 96 vs. 83%; P < 0.001). Increased progression-free survival and overall survival rates were associated with specific adverse events. Cox proportional hazard modeling adjusted for relative dose intensity and performance status established hand-foot syndrome (hazard ratio = 0.636; 95% confidence interval, 0.456-0.888) and leukopenia (hazard ratio = 0.683; 95% confidence interval, 0.492-0.948) occurring within 12 weeks were significantly correlated with increased progression-free survival. CONCLUSION: Sunitinib showed good efficacy and tolerable safety. Factors associated with greater efficacy were relative dose intensity, performance status and specific early adverse events. PMID- 26373319 TI - Long non-coding RNA UCA1 promotes glutamine metabolism by targeting miR-16 in human bladder cancer. AB - OBJECTIVE: Long non-coding ribonucleic acid urothelial carcinoma-associated 1 has been found to be a participant in cancer development and glucose metabolism in bladder cancer. However, the role of urothelial carcinoma-associated 1 in metabolic reprogramming in cancer remains to be clarified. In this study, we aim to elucidate the molecular mechanism underlying the regulation of glutamine metabolism by urothelial carcinoma-associated 1 in bladder cancer. METHODS: The RNA levels of urothelial carcinoma-associated 1, GLS2 and miR-16 in bladder tissues and cell lines were examined by real-time reverse transcriptase polymerase chain reaction. The protein levels of GLS2 were detected by western blot analysis. Reactive oxygen species generation was examined by the fluorescein isothiocyanate mean value and fluorescence microscope. Glutamine consumption was analyzed using the glutamine assay kit. Additionally, we performed luciferase reporter assays to validate urothelial carcinoma-associated 1 sequence whether contains miR-16 binding site and the interaction between the 3'UTR sequence of GLS2 and mature miR-16. RESULTS: Real-time reverse transcriptase-polymerase chain reaction demonstrated that the RNA level of urothelial carcinoma-associated 1 and GLS2 was positively correlated in bladder cancer tissues and cell lines. The expression of GLS2 mRNA and protein increased in cells which overexpression of urothelial carcinoma-associated 1 and decreased in cells which knocked-down of urothelial carcinoma-associated 1 cell lines. urothelial carcinoma-associated 1 reduced ROS production, and promoted mitochondrial glutaminolysis in human bladder cancer cells. Furthermore, luciferase reporter assays indicated that there was a miR-16 binding site in urothelial carcinoma-associated 1, and it showed appreciable levels of sponge effects on miR-16 as readouts in a dose dependent manner. Moreover, the 'seed region' of miR-16 directly bound to the 3'UTR of GLS2 mRNA and regulated GLS2 expression level. CONCLUSIONS: Together, our results revealed that urothelial carcinoma-associated 1 regulated the expression of GLS2 through interfering with miR-16, and repressed ROS formation in bladder cancer cells. PMID- 26373320 TI - Objective and subjective measures of neighborhood environment (NE): relationships with transportation physical activity among older persons. AB - BACKGROUND: This study examined the associations of subjective and objective measures of the neighbourhood environment with the transportation physical activity of community-dwelling older persons in Singapore. METHOD: A modified version of the Neighborhood Environment Walkability Scale (NEWS) and Geographical Information System (GIS) measures of the built environment characteristics were related to the frequency of walking for transportation purpose in a study sample of older persons living in high-density apartment blocks within a public housing estate in Singapore. Relevant measured variables to assess the complex relationships among built environment measures and transportation physical activity were examined using structural equation modelling and multiple regression analyses. RESULTS: The subjective measures of residential density, street connectivity, land use mix diversity and aesthetic environment and the objective GIS measure of Accessibility Index have positively significant independent associations with transportation physical activity, after adjusting for demographics, socio-economic and health status. CONCLUSION: Subjective and objective measures are non-overlapping measures complementing each other in providing information on built environment characteristics. For elderly living in a high-density urban neighborhood, well connected street, diversity of land use mix, close proximity to amenities and facilities, and aesthetic environment were associated with higher frequency of walking for transportation purposes. PMID- 26373332 TI - Blood flukes (Digenea: Aporocotylidae) infecting body cavity of South American catfishes (Siluriformes: Pimelodidae): two new species from rivers in Bolivia, Guyana and Peru with a re-assessment of Plehniella Szidat, 1951. AB - Plehniella Szidat, 1951 is emended based on new collections from South American long-whiskered catfishes. It is clearly differentiated from Sanguinicola Plehn, 1905 by lacking lateral tegumental body spines and by having 6 asymmetrical caeca. Plehniella sabajperezi sp. n. infects body cavity of Pimelodus albofasciatus (Mees) from the Demerara and Rupununi Rivers (Guyana) and Pimelodus blochii (Valenciennes) from Lake Tumi Chucua (Bolivia) and Napo River (Peru). It differs from Plehniella coelomicola Szidat, 1951 (type species) by having a thin walled vas deferens that greatly exceeds the length of cirrus-sac and that joins the cirrus-sac at level of ovovitelline duct and ootype, an internal seminal vesicle that is absent or diminutive, and a cirrus-sac that is spheroid, nearly marginal, and envelops the laterally-directed distal portion of the male genitalia. Plehniella armbrusteri sp. n. infects body cavity of P. blochii from Lake Tumi Chucua (Bolivia). It differs from P. coelomicola and P. sabajperezi by having a relatively ovoid body, a massive intestine comprising caeca that are deeply-lobed to diverticulate and terminate in the posterior half of the body, a testis that flanks the distal tips of the posteriorly-directed caeca, and a proximal portion of the vas deferens that loops ventral to the testis. Small adults (Plehniella sp.) collected from body cavity of Pimelodus grosskopfii (Steindachner) from Cienega de Jobo and Canal del Dique (Colombia) differ from congeners by having a posteriorly-constricted body region, an anterior sucker with concentric rows of minute spines, an elongate anterior oesophageal swelling, short and wide caeca, and a male genital pore that opens proportionally more anteriad. This study nearly doubles the number of aporocotylids documented from South America Rivers and comprises the first record of a fish blood fluke from P. blochii, P. albofasciatus and P. grosskopfii as well as from Bolivia, Colombia, Guyana or Peru. PMID- 26373333 TI - Correction: Catalytic enantioselective construction of quaternary stereocenters by direct vinylogous Michael addition of deconjugated butenolides to nitroolefins. AB - Correction for 'Catalytic enantioselective construction of quaternary stereocenters by direct vinylogous Michael addition of deconjugated butenolides to nitroolefins' by Madhu Sudan Manna et al., Chem. Commun., 2012, 48, 5193-5195. PMID- 26373334 TI - A Bovine Fibrinogen-Enriched Fraction as a Source of Peptides with in Vitro Renin and Angiotensin-I-Converting Enzyme Inhibitory Activities. AB - Bovine fibrinogen is currently used in the food industry as a binding agent in restructured meat products. However, this protein is underused as a source of bioactive peptides. In this study, a number of novel angiotensin-I-converting enzyme (ACE-I) and renin inhibitory peptides were identified and enriched from a bovine fibrinogen fraction. Fibrinogen was isolated and enriched from bovine blood and hydrolyzed with the food-grade enzyme papain, which was selected for use using in silico analysis. The generated hydrolysate was subjected to ultrafiltration and its peptide profile characterized by liquid chromatography tandem mass spectrometry. A number of peptides were identified and chemically synthesized to confirm their bioactivity in vitro. Identified peptides included the multifunctional tripeptide SLR, corresponding to f(35-37) of the beta-chain of bovine fibrinogen with ACE-I and renin IC50 values of 0.17 and 7.2 mM, respectively. Moreover, the resistance of identified peptides to gastrointestinal degradation and their bitterness were predicted using in silico methods. PMID- 26373335 TI - Editorial: Leadership when there are no easy answers: applying leader moral courage to wicked problems. PMID- 26373336 TI - Reproducibility of incremental maximal cycle ergometer tests in healthy recreationally active subjects. AB - PURPOSE: Testing of the ventilatory threshold (VT) and maximal oxygen uptake (VO2 peak) is relevant for the evaluation of a range of training studies, clinical trials and cross-sectional studies. Due to a possible learning effect, a familiarization test is often performed to increase test reproducibility. However, limited research has investigated this learning effect and reproducibility of maximal exercise testing. The most appropriate ways to determine VT and VO2 peak are not clear, and this study evaluated two approaches (V-slope and a combined method) for the determination of VT and five time averaging intervals (60, 30, 15, 10 and 5 s) for the determination of VO2 peak to compare test results and reproducibility. METHODS: Thirteen recreational triathletes completed three identical incremental maximal cycle ergometer tests. The initial workload was 75 and 100 watt (W) for women and men, respectively, and the workload was increased by 4 W/10 s thereafter. No familiarization test was performed. RESULTS: VO2 peak increased significantly as the time-averaging interval became shorter (e.g. 5-s interval 48.7 versus 60-s interval 44.8 ml O2 kg-1 min-1 ; overall P<0.001). All test results were similar for the three test rounds, indicating that repeated testing was not associated with any learning effect. The different VT measuring methods (CV 7.6 versus 7.7%, P = 0.58) and VO2 peak time-averaging intervals (CV 3.7-4.4%, P = 0.99) did not influence test reliability. CONCLUSIONS: The reproducibility of VT and VO2 peak was not affected by measuring methods and time-averaging intervals. However, the time-averaging intervals significantly affect the absolute VO2 peak values. Furthermore, no learning effect of maximal cycle ergometer testing was observed. PMID- 26373337 TI - Standardization of the antibody-dependent respiratory burst assay with human neutrophils and Plasmodium falciparum malaria. AB - The assessment of naturally-acquired and vaccine-induced immunity to blood-stage Plasmodium falciparum malaria is of long-standing interest. However, the field has suffered from a paucity of in vitro assays that reproducibly measure the anti parasitic activity induced by antibodies in conjunction with immune cells. Here we optimize the antibody-dependent respiratory burst (ADRB) assay, which assesses the ability of antibodies to activate the release of reactive oxygen species from human neutrophils in response to P. falciparum blood-stage parasites. We focus particularly on assay parameters affecting serum preparation and concentration, and importantly assess reproducibility. Our standardized protocol involves testing each serum sample in singlicate with three independent neutrophil donors, and indexing responses against a standard positive control of pooled hyper-immune Kenyan sera. The protocol can be used to quickly screen large cohorts of samples from individuals enrolled in immuno-epidemiological studies or clinical vaccine trials, and requires only 6 MUL of serum per sample. Using a cohort of 86 samples, we show that malaria-exposed individuals induce higher ADRB activity than malaria-naive individuals. The development of the ADRB assay complements the use of cell-independent assays in blood-stage malaria, such as the assay of growth inhibitory activity, and provides an important standardized cell-based assay in the field. PMID- 26373338 TI - Enhanced biofilm formation and multi-host transmission evolve from divergent genetic backgrounds in Campylobacter jejuni. AB - Multicellular biofilms are an ancient bacterial adaptation that offers a protective environment for survival in hostile habitats. In microaerophilic organisms such as Campylobacter, biofilms play a key role in transmission to humans as the bacteria are exposed to atmospheric oxygen concentrations when leaving the reservoir host gut. Genetic determinants of biofilm formation differ between species, but little is known about how strains of the same species achieve the biofilm phenotype with different genetic backgrounds. Our approach combines genome-wide association studies with traditional microbiology techniques to investigate the genetic basis of biofilm formation in 102 Campylobacter jejuni isolates. We quantified biofilm formation among the isolates and identified hotspots of genetic variation in homologous sequences that correspond to variation in biofilm phenotypes. Thirteen genes demonstrated a statistically robust association including those involved in adhesion, motility, glycosylation, capsule production and oxidative stress. The genes associated with biofilm formation were different in the host generalist ST-21 and ST-45 clonal complexes, which are frequently isolated from multiple host species and clinical samples. This suggests the evolution of enhanced biofilm from different genetic backgrounds and a possible role in colonization of multiple hosts and transmission to humans. PMID- 26373342 TI - Syntheses and properties of phosphine-substituted ruthenium(II) polypyridine complexes with nitrogen oxides. AB - Four novel phosphine-substituted ruthenium(ii) polypyridine complexes with nitrogen oxides-trans(P,NO2)-[Ru(trpy)(Pqn)(NO2)]PF6 (trans-NO2), cis(P,NO2) [Ru(trpy)(Pqn)(NO2)]PF6 (cis-NO2), [Ru(trpy)(dppbz)(NO2)]PF6 (PP-NO2), and cis(P,NO)-[Ru(trpy)(Pqn)(NO)](PF6)3 (cis-NO)-were synthesised (trpy = 2,2':6',2'' terpyridine, Pqn = 8-(diphenylphosphanyl)quinoline, and dppbz = 1,2 bis(diphenylphosphanyl)benzene). The influence of the number and position of the phosphine group(s) on the electronic structure of these complexes was investigated using single-crystal X-ray structural analysis, UV-vis absorption spectroscopy, and electrochemical measurements. The substitution lability of the nitrogen oxide ligand of each complex is discussed in comparison with that of the corresponding acetonitrile complexes. PMID- 26373341 TI - Parity and endometrial cancer risk: a meta-analysis of epidemiological studies. AB - The association between parity and endometrial cancer risk is inconsistent from observational studies. We aimed to quantitatively assess the relationship by summarizing all relevant epidemiological studies. PubMed (MEDLINE), Embase and Scopus were searched up to February 2015 for eligible case-control studies and prospective studies. Random-effects model was used to pool risk estimations. Ten prospective studies, 35 case-control studies and 1 pooled analysis of 10 cohort and 14 case-control studies including 69681 patients were identified. Pooled analysis revealed that there was a significant inverse association between parity and risk of endometrial cancer (relative risk (RR) for parous versus nulliparous: 0.69, 95% confidence interval (CI) 0.65-0.74; I(2) = 76.9%). By evaluating the number of parity, we identified that parity number of 1, 2 or 3 versus nulliparous demonstrated significant negative association (RR = 0.73, 95% CI 0.64 0.84, I(2) = 88.3%; RR = 0.62, 95% CI 0.53-0.74, I(2) = 92.1%; and RR = 0.68, 95% CI 0.65-0.70, I(2) = 20.0% respectively). The dose-response analysis suggested a nonlinear relationship between the number of parity and endometrial cancer risk. The RR decreased when the number of parity increased. This meta-analysis suggests that parity may be associated with a decreased risk of endometrial cancer. Further studies are warranted to replicate our findings. PMID- 26373344 TI - Office-based transurethral devascularisation of low grade non-invasive urothelial cancer using diode laser. A feasibility study. AB - BACKGROUND AND OBJECTIVE: Frequent recurrence of non-muscle invasive bladder tumours (NMIBC) requiring transurethral resection of bladder tumour (TUR-BT) and lifelong monitoring makes the lifetime cost per patient the highest of all cancers. A new method is proposed for the removal of low grade NMIBCs in an office-based setting, without the need for sedation and pain control and where the patient can leave immediately after treatment. STUDY DESIGN/PATIENTS AND METHODS: An in vitro model was developed to examine the dose/response relationship between laser power, treatment time, and distance between laser fibre and target, using a 980 nm diode laser and chicken meat. The relationship between depth and extent of tissue destruction and the laser settings was measured using microscopy and non-parametric statistical analysis. A patient with low grade stage Ta tumour and multiple comorbidity, and therefore not fit for general anaesthesia, had a tumour devascularised using the laser at the tumour base, in the outpatient department. The tumour was left in the bladder. RESULTS: In the in vitro model, depth of tissue destruction increased with laser illumination up to 30 seconds, where median depth was 4.1 mm. With longer illumination the tissue destruction levelled off. The width of tissue destruction was 2-3 mm independent of laser illumination time. The in vivo laser treatments devascularised the tumour, which was later shed from the mucosa and passed out with the urine in the days following treatment. Pain score was 0 on a visual log scale (0-10). The tumour had completely disappeared two weeks after treatment. CONCLUSION: This diode laser technique may provide almost pain-free office-based treatment of low grade urothelial cancer using flexible cystoscopes in conscious patients. A prospective randomised study will be scheduled to compare the technique with standard TUR-BT in the operating theatre. PMID- 26373346 TI - Nanoparticle Delivered VEGF-A siRNA Enhances Photodynamic Therapy for Head and Neck Cancer Treatment. AB - Photodynamic therapy (PDT) is believed to promote hypoxic conditions to tumor cells leading to overexpression of angiogenic markers such as vascular endothelial growth factor (VEGF). In this study, PDT was combined with lipid calcium-phosphate nanoparticles (LCP NPs) to deliver VEGF-A small interfering RNA (siVEGF-A) to human head and neck squamous cell carcinoma (HNSCC) xenograft models. VEGF-A were significantly decreased for groups treated with siVEGF-A in human oral squamous cancer cell (HOSCC), SCC4 and SAS models. Cleaved caspase-3 and in situ TdT-mediated dUTP nick-end labeling assay showed more apoptotic cells and reduced Ki-67 expression for treated groups compared to phosphate buffered saline (PBS) group. Indeed, the combined therapy showed significant tumor volume decrease to ~70 and ~120% in SCC4 and SAS models as compared with untreated PBS group, respectively. In vivo toxicity study suggests no toxicity of such LCP NP delivered siVEGF-A. In summary, results suggest that PDT combined with targeted VEGF-A gene therapy could be a potential therapeutic modality to achieve enhanced therapeutic outcome for HNSCC. PMID- 26373345 TI - Genome Engineering Using Adeno-associated Virus: Basic and Clinical Research Applications. AB - In addition to their broad potential for therapeutic gene delivery, adeno associated virus (AAV) vectors possess the innate ability to stimulate homologous recombination in mammalian cells at high efficiencies. This process--referred to as AAV-mediated gene targeting--has enabled the introduction of a diverse array of genomic modifications both in vitro and in vivo. With the recent emergence of targeted nucleases, AAV-mediated genome engineering is poised for clinical translation. Here, we review key properties of AAV vectors that underscore its unique utility in genome editing. We highlight the broad range of genome engineering applications facilitated by this technology and discuss the strong potential for unifying AAV with targeted nucleases for next-generation gene therapy. PMID- 26373349 TI - Highly Asymmetric Cyclopropanation With Two Sulfinyl Auxiliaries as a Way to a Useful Synthetic Intermediate. AB - The asymmetric cyclopropanation using double sulfinyl auxiliary gave bis sulfoxide with full diastereoselectivity and very high enantioselectivity. One of the sulfinyl substituents can be removed by sulfinyl metal exchange. Differentiation of sulfinyl substituents made it possible to assign the place of attack of the Grignard reagent. PMID- 26373348 TI - Regional cerebral glucose metabolism differentiates danger- and non-danger-based traumas in post-traumatic stress disorder. AB - Post-traumatic stress disorder (PTSD) is presumably the result of life threats and conditioned fear. However, the neurobiology of fear fails to explain the impact of traumas that do not entail threats. Neuronal function, assessed as glucose metabolism with (18)fluoro-deoxyglucose positron emission tomography, was contrasted in active duty, treatment-seeking US Army Soldiers with PTSD endorsing either danger- (n = 19) or non-danger-based (n = 26) traumas, and was compared with soldiers without PTSD (Combat Controls, n = 26) and Civilian Controls (n = 24). Prior meta-analyses of regions associated with fear or trauma script imagery in PTSD were used to compare glucose metabolism across groups. Danger-based traumas were associated with higher metabolism in the right amygdala than the control groups, while non-danger-based traumas associated with heightened precuneus metabolism relative to the danger group. In the danger group, PTSD severity was associated with higher metabolism in precuneus and dorsal anterior cingulate and lower metabolism in left amygdala (R(2 )= 0.61). In the non-danger group, PTSD symptom severity was associated with higher precuneus metabolism and lower right amygdala metabolism (R(2 )= 0.64). These findings suggest a biological basis to consider subtyping PTSD according to the nature of the traumatic context. PMID- 26373350 TI - Giant Bowen's disease histologically showing Borst-Jadassohn phenomenon and complicated with squamous cell carcinoma development. PMID- 26373347 TI - Activation of Cyclic Adenosine Monophosphate Pathway Increases the Sensitivity of Cancer Cells to the Oncolytic Virus M1. AB - Oncolytic virotherapy is a novel and emerging treatment modality that uses replication-competent viruses to destroy cancer cells. Although diverse cancer cell types are sensitive to oncolytic viruses, one of the major challenges of oncolytic virotherapy is that the sensitivity to oncolysis ranges among different cancer cell types. Furthermore, the underlying mechanism of action is not fully understood. Here, we report that activation of cyclic adenosine monophosphate (cAMP) signaling significantly sensitizes refractory cancer cells to alphavirus M1 in vitro, in vivo, and ex vivo. We find that activation of the cAMP signaling pathway inhibits M1-induced expression of antiviral factors in refractory cancer cells, leading to prolonged and severe endoplasmic reticulum (ER) stress, and cell apoptosis. We also demonstrate that M1-mediated oncolysis, which is enhanced by cAMP signaling, involves the factor, exchange protein directly activated by cAMP 1 (Epac1), but not the classical cAMP-dependent protein kinase A (PKA). Taken together, cAMP/Epac1 signaling pathway activation inhibits antiviral factors and improves responsiveness of refractory cancer cells to M1-mediated virotherapy. PMID- 26373351 TI - Effects of arm-splint rigidity on self-injury and adaptive behavior. AB - The current study replicated and extended previous research on the use of a rapid assessment to identify effective arm-splint rigidity with 2 participants who had been diagnosed with autism and who engaged in self-injurious behavior (SIB). We varied rigidity levels within a multielement design across several adaptive tasks and identified the most effective rigidity level in terms of reductions in SIB and levels of compliance. PMID- 26373352 TI - Horn fly larval survival in cattle dung is reduced by endophyte infection of tall fescue pasture. AB - BACKGROUND: The potential for using endophytic microorganisms in pest control has increased during the last 40 years. In this study, we investigated the impact of endophyte (Neotyphodium coenophialum) infection of cattle pasture upon the survival of the horn fly, Haematobia irritans, a major agricultural pest affecting livestock in many parts of the world. RESULTS: In laboratory assays, where cattle dung collected from endophyte-infected (E+) tall fescue cultivar K 31 was used as the oviposition substrate, larval development was significantly reduced compared with development on cattle dung from steers that grazed uninfected (E-) tall fescue. Furthermore, studies with cattle dung supplemented with the alkaloid fraction extracted from the endophytic fungi revealed significant larval mortality, and HPLC analysis identified two alkaloids, peramine and lolitrem B. The development of larvae was shown to be significantly reduced in field-collected cattle dung. These results suggest that part of the toxicity of alkaloids contained in endophytes is transferred to faecal matter, causing an increase in mortality of H. irritans. CONCLUSION: These data suggest that endophyte infection of cattle pasture, i.e. modified pasture management, can significantly affect horn fly development. (c) 2015 Society of Chemical Industry. PMID- 26373353 TI - Computerised cognitive testing of individuals with Down's syndrome and Alzheimer's disease. AB - BACKGROUND: Although Alzheimer's disease neuropathology is present by age 40 years, in Down's syndrome, ante-mortem diagnosis is difficult. No standard for cognitive assessment is well established or easy to administer. METHOD: We used a simple, widely available computerised test (NeuroTrax Moderate to Severe Impairment Assessment Battery, Mindstreams, Newark, NJ) to evaluate 14 patients in this population. Orientation, memory, executive function, verbal function and visual spatial function were evaluated every 6 months for 18 months. RESULTS: Mean scaled scores in this longitudinal study were evaluated with repeated measures analysis of variance. Memory, executive function, verbal function and visual spatial function scores did not significantly change. There was no significant depression or anxiety on self-reported measures. CONCLUSIONS: Reproducibility of test results supports the reliability of this battery to quantify function and prospectively follow performance in this population over an 18-month period. PMID- 26373355 TI - (19)F MRSI of capecitabine in the liver at 7 T using broadband transmit-receive antennas and dual-band RF pulses. AB - Capecitabine (Cap) is an often prescribed chemotherapeutic agent, successfully used to cure some patients from cancer or reduce tumor burden for palliative care. However, the efficacy of the drug is limited, it is not known in advance who will respond to the drug and it can come with severe toxicity. (19)F Magnetic Resonance Spectroscopy (MRS) and Magnetic Resonance Spectroscopic Imaging (MRSI) have been used to non-invasively study Cap metabolism in vivo to find a marker for personalized treatment. In vivo detection, however, is hampered by low concentrations and the use of radiofrequency (RF) surface coils limiting spatial coverage. In this work, the use of a 7T MR system with radiative multi-channel transmit-receive antennas was investigated with the aim of maximizing the sensitivity and spatial coverage of (19)F detection protocols. The antennas were broadband optimized to facilitate both the (1)H (298 MHz) and (19)F (280 MHz) frequencies for accurate shimming, imaging and signal combination. B1(+) simulations, phantom and noise measurements showed that more than 90% of the theoretical maximum sensitivity could be obtained when using B1(+) and B1(-) information provided at the (1)H frequency for the optimization of B1(+) and B1( ) at the (19)F frequency. Furthermore, to overcome the limits in maximum available RF power, whilst ensuring simultaneous excitation of all detectable conversion products of Cap, a dual-band RF pulse was designed and evaluated. Finally, (19)F MRS(I) measurements were performed to detect (19)F metabolites in vitro and in vivo. In two patients, at 10 h (patient 1) and 1 h (patient 2) after Cap intake, (19)F metabolites were detected in the liver and the surrounding organs, illustrating the potential of the set-up for in vivo detection of metabolic rates and drug distribution in the body. PMID- 26373359 TI - All-Solid-State Lithium-Ion Batteries with Grafted Ceramic Nanoparticles Dispersed in Solid Polymer Electrolytes. AB - Lithium-based rechargeable batteries offer superior specific energy and power, and have enabled exponential growth in industries focused on small electronic devices. However, further increases in energy density, for example for electric transportation, face the challenge of harnessing the lithium metal as negative electrode instead of limited-capacity graphite and its heavy copper current collector. All-solid-state batteries utilize solid polymer electrolytes (SPEs) to overcome the safety issues of liquid electrolytes. We demonstrate an all-solid state lithium-ion battery by using plasticized poly(ethylene oxide)-based SPEs comprising anions grafted or co-grafted onto ceramic nanoparticles. This new approach using grafted ceramic nanoparticles enables the development of a new generation of nanohybrid polymer electrolytes with high ionic conductivity as well as high electrochemical and mechanical stability, enabling Li-ion batteries with long cycle life. PMID- 26373354 TI - Identification of a VxP Targeting Signal in the Flagellar Na+ /K+ -ATPase. AB - Na(+) /K(+) -ATPase (NKA) participates in setting electrochemical gradients, cardiotonic steroid signaling and cellular adhesion. Distinct isoforms of NKA are found in different tissues and subcellular localization patterns. For example, NKA alpha1 is widely expressed, NKA alpha3 is enriched in neurons and NKA alpha4 is a testes-specific isoform found in sperm flagella. In some tissues, ankyrin, a key component of the membrane cytoskeleton, can regulate the trafficking of NKA. In the retina, NKA and ankyrin-B are expressed in multiple cell types and immunostaining for each is striking in the synaptic layers. Labeling for NKA is also prominent along the inner segment plasma membrane (ISPM) of photoreceptors. NKA co-immunoprecipitates with ankyrin-B, but on a subcellular level colocalization of these two proteins varies dependent on the cell type. We used transgenic Xenopus laevis tadpoles to evaluate the subcellular trafficking of NKA in photoreceptors. GFP-NKA alpha3 and alpha1 are localized to the ISPM, but alpha4 is localized to outer segments (OSs). We identified a VxP motif responsible for the OS targeting by using a series of chimeric and mutant NKA constructs. This motif is similar to previously identified ciliary targeting motifs. Given the structural similarities between OSs and flagella, our findings shed light on the subcellular targeting of this testes-specific NKA isoform. PMID- 26373360 TI - Deuterium-Labeling Study of the Hydrogenation of 2-Methylfuran and 2,5 Dimethylfuran over Carbon-Supported Noble Metal Catalysts. AB - 2-Methylfuran and 2,5-dimethylfuran were deuterated over Pd and Pt catalysts at 90-220 degrees C. Furan ring saturation over a Pd/C catalyst occurred at low reaction temperatures, which led to deuterated THFs, followed by progressive D exchange in the THF ring at higher temperatures. Finally, H/D exchange occurred in the methyl groups on the THF ring. Cleavage of the C-O bond also occurred over a Pd/C catalyst at elevated temperatures, which resulted in deuterated ketones, for which all H atoms were exchanged for D. Alcohols were produced over a Pt/C catalyst at low temperatures because they are more stable than the corresponding ketones. D replaced H on all carbon atoms of the furan ring and saturated the O and C atoms of the broken C-O bond in both deuterated 2-pentanol and 2-hexanol. At low temperatures (90-105 degrees C), all H atoms in the deuterated alcohols were exchanged for D except for the last two hydrogen atoms on the methyl groups. PMID- 26373361 TI - Visible-Light-Driven Oxidation of Organic Substrates with Dioxygen Mediated by a [Ru(bpy)3 ](2+) /Laccase System. AB - Oxidation reactions are highly important chemical transformations that still require harsh reaction conditions and stoichiometric amounts of chemical oxidants that are often toxic. To circumvent these issues, olefins oxidation is achieved in mild conditions upon irradiation of an aqueous solution of the complex [Ru(bpy)3 ](2+) and the enzyme laccase. Epoxide formation is coupled to the light driven reduction of O2 by [Ru(bpy)3 ](2+) /laccase system. The reactivity can be explained by dioxygen acting both as an oxidative agent and as renewable electron acceptor, avoiding the use of a sacrificial electron acceptor. PMID- 26373362 TI - Biomass-Derived Heteroatom-Doped Carbon Aerogels from a Salt Melt Sol-Gel Synthesis and their Performance in Li-S Batteries. AB - An ionothermal sol-gel strategy to synthesize hierarchically porous carbon aerogels doped with different heteroatoms is presented by using biomass precursors in a scalable process. Morphologically similar but chemically different materials are used to study the influence of heteroatoms in Li-S batteries. The materials show capacities as high as 1290 mAh g(-1) in the first cycle using 50 wt % S loading. Heteroatom doping reduces the capacity fading and the polarization throughout cycling. Zeta potential measurements reveal positive surface charges for heteroatom-doped carbons and indicate attractive interactions with polysulfides causing reduced fading. A polysulfide-selective sorption study reveals strongly different adsorption behavior depending on the carbon's chemical composition. Interestingly, the polysulfide fraction is also crucial. The results indicate that improved adsorption of long-chain polysulfides to doped carbons is related to improved capacity retention. PMID- 26373363 TI - Highly Active and Durable Nanocrystal-Decorated Bifunctional Electrocatalyst for Rechargeable Zinc-Air Batteries. AB - A highly active and durable bifunctional electrocatalyst that consists of cobalt oxide nanocrystals (Co3 O4 NC) decorated on the surface of N-doped carbon nanotubes (N-CNT) is introduced as effective electrode material for electrically rechargeable zinc-air batteries. This active hybrid catalyst is synthesized by a facile surfactant-assisted method to produce Co3 O4 NC that are then decorated on the surface of N-CNT through hydrophobic attraction. Confirmed by half-cell testing, Co3 O4 NC/N-CNT demonstrates superior oxygen reduction and oxygen evolution catalytic activities and has a superior electrochemical stability compared to Pt/C and Ir/C. Furthermore, rechargeable zinc-air battery testing of Co3 O4 NC/N-CNT reveals superior galvanodynamic charge and discharge voltages with a significantly extended cycle life of over 100 h, which suggests its potential as a replacement for precious-metal-based catalysts for electric vehicles and grid energy storage applications. PMID- 26373364 TI - Isolation of Renewable Phenolics by Adsorption on Ultrastable Hydrophobic MIL-140 Metal-Organic Frameworks. AB - The isolation and separation of phenolic compounds from aqueous backgrounds is challenging and will gain in importance as we become more dependent on phenolics from lignocellulose-derived bio-oil to meet our needs for aromatic compounds. Herein, we show that highly stable and hydrophobic Zr metal-organic frameworks of the MIL-140 type are effective adsorbent materials for the separation of different phenolics and far outperform other classes of porous solids (silica, zeolites, carbons). The mechanism of the hydroquinone-catechol separation on MIL 140C was studied in detail by combining experimental results with computational techniques. Although the differences in adsorption enthalpy between catechol and hydroquinone are negligible, the selective uptake of catechol in MIL-140C is explained by its dense pi-pi stacking in the pores. The interplay of enthalpic and entropic effects allowed separation of a complex, five-compound phenol mixture through breakthrough over a MIL-140C column. Unlike many other metal organic frameworks, MIL-140C is remarkably stable and maintained structure, porosity and performance after five adsorption-desorption cycles. PMID- 26373369 TI - Bacterial evolution: To divide and conquer. PMID- 26373370 TI - How apicomplexans became free-riders. PMID- 26373371 TI - Outer-membrane vesicles from Gram-negative bacteria: biogenesis and functions. AB - Outer-membrane vesicles (OMVs) are spherical buds of the outer membrane filled with periplasmic content and are commonly produced by Gram-negative bacteria. The production of OMVs allows bacteria to interact with their environment, and OMVs have been found to mediate diverse functions, including promoting pathogenesis, enabling bacterial survival during stress conditions and regulating microbial interactions within bacterial communities. Additionally, because of this functional versatility, researchers have begun to explore OMVs as a platform for bioengineering applications. In this Review, we discuss recent advances in the study of OMVs, focusing on new insights into the mechanisms of biogenesis and the functions of these vesicles. PMID- 26373373 TI - Cooperative development of antimicrobials: looking back to look ahead. AB - As foundations and governments mobilize to tackle antimicrobial resistance (AMR), several experiments in academic-industrial collaboration have emerged. Here, I examine two historical precedents, the Penicillin Project and the Malaria Project of the Second World War, and two contemporary examples, the Tuberculosis Drug Accelerator programme and the Tres Cantos Open Lab. These and related experiments suggest that different strategies can be effective in managing academic industrial collaborations, and that such joint projects can prosper in both multisite and single-site forms, depending on the specific challenges and goals of each project. The success of these strategies and the crisis of AMR warrant additional investment in similar projects. PMID- 26373372 TI - A new perspective on lysogeny: prophages as active regulatory switches of bacteria. AB - Unlike lytic phages, temperate phages that enter lysogeny maintain a long-term association with their bacterial host. In this context, mutually beneficial interactions can evolve that support efficient reproduction of both phages and bacteria. Temperate phages are integrated into the bacterial chromosome as large DNA insertions that can disrupt gene expression, and they may pose a fitness burden on the cell. However, they have also been shown to benefit their bacterial hosts by providing new functions in a bacterium-phage symbiotic interaction termed lysogenic conversion. In this Opinion article, we discuss another type of bacterium-phage interaction, active lysogeny, in which phages or phage-like elements are integrated into the bacterial chromosome within critical genes or operons and serve as switches that regulate bacterial genes via genome excision. PMID- 26373375 TI - Rutosides for prevention of post-thrombotic syndrome. AB - BACKGROUND: Post-thrombotic syndrome (PTS) is a long-term complication of deep venous thrombosis (DVT) that is characterised by pain, swelling, and skin changes in the affected limb. One in three patients with DVT will develop post-thrombotic sequelae within five years. The current standard care for the prevention of PTS following DVT is elastic compression stockings. Rutosides are a group of compounds derived from horse chestnut (Aesculus hippocastanum), a traditional herbal remedy for treating oedema formation in chronic venous insufficiency (CVI). However, it is not known whether rutosides are effective and safe in the prevention of post-thrombotic syndrome. This is an update of the review first published in 2013. OBJECTIVES: To determine the effectiveness and safety of rutosides for prevention of PTS in patients with DVT, compared to placebo, no intervention, or reference medication. SEARCH METHODS: For this update the Cochrane Vascular Group Trials Search Co-ordinator searched the Specialised Register (last searched September 2015) and the Cochrane Register of Studies (CRS) ((CENTRAL) 2015, Issue 8). Clinical trials databases were searched for details of ongoing and unpublished studies. SELECTION CRITERIA: We planned to include trials of rutosides versus any alternative (placebo, no intervention, or reference medication) in the prevention of PTS in patients with DVT. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion and intended to extract information from the trials. MAIN RESULTS: No studies were identified comparing rutosides versus any alternative in the prevention of PTS. AUTHORS' CONCLUSIONS: As there were no studies identified in this review there is currently insufficient evidence to determine the effectiveness and safety of rutosides for prevention of PTS in patients with DVT. Some studies suggest that rutosides may provide short-term relief of PTS symptoms. However, there is nothing published on their use as a preventative therapy for PTS. High quality randomised controlled trials of rutoside versus any alternative are required to build the evidence base in this area. PMID- 26373374 TI - Signatures of selection in tilapia revealed by whole genome resequencing. AB - Natural selection and selective breeding for genetic improvement have left detectable signatures within the genome of a species. Identification of selection signatures is important in evolutionary biology and for detecting genes that facilitate to accelerate genetic improvement. However, selection signatures, including artificial selection and natural selection, have only been identified at the whole genome level in several genetically improved fish species. Tilapia is one of the most important genetically improved fish species in the world. Using next-generation sequencing, we sequenced the genomes of 47 tilapia individuals. We identified a total of 1.43 million high-quality SNPs and found that the LD block sizes ranged from 10-100 kb in tilapia. We detected over a hundred putative selective sweep regions in each line of tilapia. Most selection signatures were located in non-coding regions of the tilapia genome. The Wnt signaling, gonadotropin-releasing hormone receptor and integrin signaling pathways were under positive selection in all improved tilapia lines. Our study provides a genome-wide map of genetic variation and selection footprints in tilapia, which could be important for genetic studies and accelerating genetic improvement of tilapia. PMID- 26373377 TI - A taxonomic review of white grubs and leaf chafers (Coleoptera: Scarabaeidae: Melolonthinae) recorded from forestry and agricultural crops in Sub-Saharan Africa. AB - Integrated pest management (IPM) is difficult to implement when one knows little about the pest complex or species causing the damage in an agricultural system. To implement IPM on Sub-Saharan African melolonthine pests access to taxon specific knowledge (their identity) and what is known (their biology) of potential pest species is a crucial step. What is known about Sub-Saharan African melolonthine white grubs and chafers has not yet been amalgamated, and this review thus synthesizes all available literature for the Region. The comprehensive nature of the review highlights pest taxon trends within African melolonthines. To facilitate the retrieval of this information for IPM purposes, all relevant taxonomic and biological information is provided for the taxa covered including an on-line supplementary annotated-checklist of taxon, crop, locality and reference(s). Based on the literature reviewed, recommendations are made to promote effective and efficient management of African melolonthine scarab pests. An on-line supplementary appendix provides a list of specialists, useful internet resources, keys, catalogues and sampling methods for the larvae and adults of melolonthine scarab beetles for subsequent morphological or molecular work. PMID- 26373378 TI - A Compact "Water Window" Microscope with 60 nm Spatial Resolution for Applications in Biology and Nanotechnology. AB - Short illumination wavelength allows an extension of the diffraction limit toward nanometer scale; thus, improving spatial resolution in optical systems. Soft X ray (SXR) radiation, from "water window" spectral range, lambda=2.3-4.4 nm wavelength, which is particularly suitable for biological imaging due to natural optical contrast provides better spatial resolution than one obtained with visible light microscopes. The high contrast in the "water window" is obtained because of selective radiation absorption by carbon and water, which are constituents of the biological samples. The development of SXR microscopes permits the visualization of features on the nanometer scale, but often with a tradeoff, which can be seen between the exposure time and the size and complexity of the microscopes. Thus, herein, we present a desk-top system, which overcomes the already mentioned limitations and is capable of resolving 60 nm features with very short exposure time. Even though the system is in its initial stage of development, we present different applications of the system for biology and nanotechnology. Construction of the microscope with recently acquired images of various samples will be presented and discussed. Such a high resolution imaging system represents an interesting solution for biomedical, material science, and nanotechnology applications. PMID- 26373379 TI - Negatively charged AuNP modified with monoclonal antibody against novel tumor antigen FAT1 for tumor targeting. AB - BACKGROUND: Herein, we demonstrated the use of a newly generated anti FAT1 antibody (clone mAB198.3) for intracellular delivery of anionic gold NPs, to form active targeting Au nanoparticles with high payload characteristics. METHODS: In vitro characterizations were determined by DLS, confocal microscopy, TEM, western blot, MALDI-TOF MS/MS analysis, MTT, ICP-MS and flow cytometry analysis. In vivo targeting efficacy was investigated by in vivo bio-imaging study and ICP-MS. RESULTS: The specificity of the FAT1 recognition in colon cancer was confirmed by pre-adsorbing mAb198.3, adsorption dramatically abolished the antibody reactivity on colon cancer, thus confirming the binding specificity. The DLS size distribution profile of the AuCOOH, AuCOOH(Cy5)_ mAb198.3, AuCOOH(Cy5)_isotype has showed that the modified gold nanoparticles are well dispersed in water, PBS buffer and cell culture medium with 10 % FBS. By TEM measurement, the size of Au nanoparticles with spherical morphology is about 10-20 nm. AuCOOH_198.3 NPs were stable in an acidic environment, as well as in PBS buffer, cell culture media and media with 10 % serum. MTT results revealed that Au nanoparticles have well biocompatibility. TEM results indicated that conjugation of mAb198.3 on Au nanoparticles can be an effective delivery vehicle for negatively charged gold nanoparticles and increased its intracellular transport. It was also demonstrated by confocal microscopy that AuCOOH(Cy5)_mAb198.3 could attach to the cell membrane in very short time, then gradually delivered into cells. After 4 h incubation, almost all AuCOOH(Cy5)_mAb198.3 have been uptaken into or surrounding the cytoplasm and nucleus. In vivo results showed that only about 20 % of AuCOOH accumulated in tumor site due to EPR effect, while nearly 90 % of AuCOOH_mAb198.3 was found in tumor, providing sufficient evidence for receptor-specific targeting by mAb198.3. CONCLUSION: According to in vitro and in vivo research results, the intracellular uptake of negatively charged AuCOOH_mAB198.3 particles is enhanced to a greater extent. Thus, AuCOOH_mAb198.3 holds significant potential to improve the treatment of cancer. PMID- 26373381 TI - Does the rate of cervical shortening after cerclage predict preterm birth? AB - OBJECTIVE: The objective of this study is to evaluate whether the rate of cervical shortening after cerclage can predict spontaneous preterm birth (SPTB). METHODS: Women who had cervical length (CL) assessments after cerclage placement were identified. The rate of cervical shortening and its relationship with SPTB was established using a generalized linear regression model. Secondary outcomes included relationship between cervical shortening and risk of SPTB in those with a post-cerclage CL <25 mm versus >=25 mm at 18-20 weeks; and the rate of cervical shortening in women who delivered preterm compared with those who delivered at term. RESULTS: One hundred thirty-four patients were included and 30 (22.4%) delivered at <36 weeks. A rate of cervical shortening of 1 mm/week conferred a risk of SPTB of 22%. Among women with cerclage who had a CL <25 mm at 18-20 weeks, 1 mm/week of cervical shortening was associated with a 59% risk of SPTB. Patients with cerclage who delivered at term had a slower rate of cervical shortening compared to those who delivered preterm (0.62 mm versus 1.40 mm per week, p = 0.008). CONCLUSIONS: The rate of cervical shortening after cerclage placement is associated with the risk of SPTB. Sonographic surveillance of the rate of cervical shortening may be useful in assessing risk for SPTB in patients with cerclage. PMID- 26373380 TI - Brain metabolism and cerebrospinal fluid biomarkers profile of non-amnestic mild cognitive impairment in comparison to amnestic mild cognitive impairment and normal older subjects. AB - INTRODUCTION: Mild cognitive impairment (MCI) is classically considered a transitional stage between normal aging and dementia. Non-amnestic MCI (naMCI) patients, however, typically demonstrate cognitive deficits other than memory decline. Furthermore, as a group, naMCI have a lower rate of an eventual dementia diagnosis as compared to amnestic subtypes of MCI (aMCI). Unfortunately, studies investigating biomarker profiles of naMCI are scarce. The study objective was to investigate the regional brain glucose metabolism (rBGM) with [18F]FDG-PET and cerebrospinal fluid (CSF) biomarkers in subjects with naMCI as compared to a control group (CG) and aMCI subjects. METHODS: Ninety-five patients were included in three different groups: naMCI (N = 32), aMCI (N = 33) and CG (N = 30). Patients underwent brain MRI and [18F]FDG-PET. A subsample (naMCI = 26, aMCI = 28) also had an assessment of amyloid-beta, tau, and phosphorylated tau levels in the CSF. RESULTS: Both MCI groups had lower rBGM in relation to the CG in the precuneus. Subjects with naMCI showed decreased right prefrontal metabolism as well as higher levels of CSF amyloid-beta relative to aMCI subjects. CONCLUSION: While amnestic MCI subjects showed a biomarker profile classically related to MCI due to Alzheimer's disease, naMCI patients illustrated a decrease in both prefrontal hypometabolism and higher CSF amyloid-beta levels relative to the aMCI group. These biomarker findings indicate that naMCI is probably a heterogeneous group with similar precuneus hypometabolism compared to aMCI, but additional frontal hypometabolism and less amyloid-beta deposition in the brain. Clinical follow-up and reappraisal of biomarkers of the naMCI group is needed to determine the outcome and probable etiological diagnosis. PMID- 26373382 TI - [Ethical Aspects of Internet-Mediated Research]. PMID- 26373383 TI - [Inpatient Dialectical Behavioral Therapy for Adolescents (DBT-A) - 10 years of experience on the psychiatric inpatient unit "wellenreiter"]. AB - In April 2004 the inpatient unit "Wellenreiter" at the Vorwerker Clinic for Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy in Lubeck (Germany) opened its doors. Despite reservations by the therapeutic community, we implemented a specialized treatment for female adolescents with symptoms of borderline personality disorder - the I;>ialectical Behavior Therapy for Adolescents (DBT-A). In this article we present the concept, our experiences, and data from the past 10 years of clinical work in this specialized unit. PMID- 26373384 TI - [Cognitive and affective perspective-taking in girls with conduct problems as a function of the callous-unemotional personality feature]. AB - OBJECTIVE: Do girls with conduct problems (CP) and callous-unemotional (CU) traits show specific deficits in perspective-taking (PT) compared to healthy girls? METHOD: We examined cognitive and affective PT in girls with CP and high CU scores (SVP-CU+), girls with CP and low CU-scores (SVP-CU-), and a healthy control group (KG) using a video sequence task and the animated shapes task. The sample consisted of 59 girls aged 8;6 to 16; 11 years. RESULTS: The groups did not differ in affective or in cognitive PT. CONCLUSION: The results emphasize the necessity of studies of PT in girls with CP and CU traits that account for differences in age ,and gender. PMID- 26373385 TI - Adolescent Defense Style as Correlate of Problem Behavior. AB - OBJECTIVE: Adolescent problem behaviors are often the visible results of intrapsychic distress. Defensive reactions are the unconscious means of managing intrapsychic distress. This cross-sectional study examines the strength of defensive style as measured by self-report on the Response Evaluation Measure (REM-71) relative to age, sex, and SES, as a correlate of internalizing and externalizing problem behaviors, as assessed by the Youth Self Report (YSR). METHODS: A sample of 1,487 students from two suburban high schools completed self report measures of defense style, self-esteem, and internalizing and externalizing problem behaviors. Demographic variables (age, sex, and SES) were included as covariates. RESULTS: Mature and immature defense style correlated as expected with problem behaviors. Demographic variables contributed minimally to the variance in the outcome variable. CONCLUSIONS: Defense style, as assessed by the REM-71, is a significant correlate of clinically elevated internalizing and externalizing problem behaviors in youth as in adults. This study adds to the convergent validity of the REM-71. PMID- 26373386 TI - Cognitive Remediation Therapy for Children with Anorexia Nervosa. AB - OBJECTIVE: Evidence-based treatment programs for children with anorexia nervosa (AN) are scarce, while their prognosis is negative and the incidence rate rises. A new therapeutic approach recently received positive attention: cognitive remediation therapy (CRT). This intervention targets inflexibility and the inability to perceive the bigger picture in persons with AN. So far, studies and case reports have focused on either adolescent or adult patients and less on young children with AN. This case report therefore describes and evaluates the implementation of CRT with a child with AN. METHOD: A 12-year-old girl with severe chronic AN was treated with 10 sessions of CRT. Her clinical and neuropsychological evaluations before, directly after and 7 months after CRT are reported. Additionally, the patient's written and verbal feedbacks are reviewed. RESULTS: At the 7-month follow-up the patient showed a stable healthy weight and reported a reduced presence of psychopathology. Her neuropsychological performance directly after CRT and after 7 months did not improve. CONCLUSIONS: The clinical evaluation of our case report suggests that CRT may be a promising add-on therapy in the clinical treatment of young girls with AN. PMID- 26373387 TI - [Participation of traumatized children and adolescents affected by provisional safeguards (removal and custody of children ace. to Para. 42 SGB VIII)_]. AB - OBJECTIVE: This study analyzes important variables of settings of children taken into state custody and records trauma exposure. METHOD: 52 children and adolescents with e~periences of removal and custody were questioned online in the social network Facebook. Traumatic stressors before removal and custody were assessed as well as the reasons that lead .to removal and custody and the subsequent burdens. RESULTS: In more than every other case the children and adolescents reported that they were not involved in important decisions during removal and custody. After termination of the removal and custody process, 50% did not want to return to their parents. Compared to children wanting to return to their parents, children who did not want to return home display signs of severe physical and emotional neglect as well as extreme physical abuse. Even though they have no desire to return, they are often sent back to their parents against their will. CONCLUSIONS: Children who are removed and put in state custody should be included when deciding important questions. Whether or not they wish to return to their parents should be taken into consideration more strongly. Children who are sent back to theirparents against their will suffer from on going traumatization. PMID- 26373391 TI - Size is an essential parameter in governing the UVB-protective efficacy of silver nanoparticles in human keratinocytes. AB - BACKGROUND: Ultraviolet (UV) radiation from sun, particularly its UVB component (290-320 nm), is considered the major etiological cause of skin cancer that impacts over 2 million lives in the United States alone. Recently, we reported that polydisperse colloidal suspension of silver nanoparticles (AgNPs) protected the human keratinocytes (HaCaT) against UVB-induced damage, thus indicating their potential for prevention of skin carcinogenesis. Here we sought out to investigate if size controlled the chemopreventive efficacy of AgNPs against UVB induced DNA damage and apoptosis. METHODS: Percent cell viability was examined by WST-1 assay after treating the cells with various doses (1-10 MUg/mL) of AgNPs of different sizes (10, 20, 40, 60 and 100 nm) for 12 and 24 h. For protection studies, cells were treated with AgNPs of different sizes at a uniform concentration of 1 MUg/mL. After 3 h, cells were irradiated with UVB (40 mJ/cm(2)) and dot-blot analysis was performed to detect cyclobutane pyrimidine dimers (CPDs) as an indication of DNA damage. Apoptosis was analyzed by flow cytometry after staining the cells with 7-Amino-Actinomycin (7-AAD) and PE Annexin V. Immunoblot analysis was accomplished by processing the cells for protein extraction and Western blotting using specific antibodies against various proteins. RESULTS: The data show that the pretreatment of HaCaT cells with AgNPs in the size range of 10-40 nm were effective in protecting the skin cells from UVB radiation-induced DNA damage as validated by reduced amounts of CPDs, whereas no protection was observed with AgNPs of larger sizes (60 and 100 nm). Similarly, only smaller size AgNPs (10-40 nm) were effective in protecting the skin cells from UV radiation-induced apoptosis. At the molecular level, UVB -irradiation of HaCaT cells led to marked increase in expression of pro-apoptotic protein (Bax) and decrease in anti-apoptotic proteins (Bcl-2 and Bcl-xL), while it remained largely unaffected in skin cells pretreated with smaller size AgNPs (10-40 nm). CONCLUSIONS: Altogether, these findings suggest that size is a critical determinant of the UVB-protective efficacy of AgNPs in human keratinocytes. PMID- 26373392 TI - Blastocystis specific serum immunoglobulin in patients with irritable bowel syndrome (IBS) versus healthy controls. AB - BACKGROUND: Blastocystis species are common enteric human parasites and carriage has been linked to Irritable Bowel Syndrome (IBS), particularly diarrhoea predominant IBS. The spectrum of immune reactivity to Blastocystis proteins has been reported previously in symptomatic patients. We investigated differences in serum immunoglobulin profiles between patients with IBS, both positive and negative for Blastocystis carriage, and healthy controls (HC). METHODS: Forty diarrhoea-predominant IBS patients (26 patients positive for Blastocystis sp., 14 negative patients) and forty HC (24 positive, 16 Blastocystis-negative) were enrolled. Age, gender, ethnicity and serum immunoglobulin A (IgA) levels were recorded and faecal specimens were analysed using smear, culture and polymerase chain reaction amplification of ribosomal DNA. Sera were tested in Western blots and the reactivities compared to known targets using monoclonal antibodies Blastofluor(r) (Blastocystis specific antibody), MAb1D5 (cytopathicto Blastocystis cells), anti-promatrix metalloprotease-9 (anti-MMP-9) and SDS-PAGE zymograms. RESULTS: Levels of serum IgA were significantly lower in Blastocystis carriers (p < 0.001) but had no relationship to symptoms. Western blots demonstrated serum IgG antibodies specific for Blastocystis proteins of 17,27,37,50,60-65, 75-90, 95-105 and 150 kDa MW. Reactivity to the 27, 50 and 75 95 kDa proteins were found more frequently in the IBS group compared to the HC's (p < 0.001) and correlation was greater for Blastocystis-positive IBS patients (p < 0.001) than for negative IBS patients (p < 0.05). MAb1D5 reacted with proteins of 27 and 100 kDa, and anti-MMP-9 with 27, 50 and 75-100 kDa proteins. Bands were seen in zymograms around 100 kDa. CONCLUSIONS: Low serum IgA levels are associated with Blastocystis carriage. All IBS patients were more likely to demonstrate reactivity with Blastocystis proteins of 27 kDa (likely a cysteine protease), 50 and 75-95 kDa MW compared to HC. The presence of antibodies to these Blastocystis proteins in some Blastocystis-negative subjects suggests either prior exposure to Blastocystis organisms or antibody cross reactivities. The anti-proMMP-9 reaction at 50 and 75-100 kDa and the zymogram result suggest that metalloproteases may be important Blastocystis antigens. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials registry ACTRN: 12611000918921. PMID- 26373393 TI - Up-regulation of microRNA-16 in Glioblastoma Inhibits the Function of Endothelial Cells and Tumor Angiogenesis by Targeting Bmi-1. AB - BACKGROUND: Angiogenesis is an important process facilitating the growth of glioblastoma (GBM). It also has drawn great attention in the treatment of GBM. GBM angiogenesis is closely related to the function of endothelial cells. microRNAs can affect the activities of endothelial 10 cells directly, or indirectly through the interaction of tumor cells and endothelial cells. However, the mechanism underlying the interaction of GBM cells regulated by specific microRNA with endothelial cells and following angiogenesis requires further research. In published articles, microRNA-16 acted as a tumor suppressor in multiple types of cancers including glioma, but the role in glioma angiogenesis has not been well elucidated. METHODS: The expression of microRNA-16 was detected in human GBM samples and normal brain tissues. microRNA-16 was transfected to GBM cell line U87 and A172 then the function of endothelial cells co-cultured with U87/A172 (miR-16 or control) were observed in vitro. Expression of VEGF family in vitro and the effect of microRNA-16 on GBM angiogenesis in vivo were also investigated. RESULTS: microRNA-16 is down-regulated in human GBM samples in contrast to the normal brain tissues. Overexpression of microRNA- 16 in the A172 and U87 GBM cell lines inhibited the activities of co-cultured endothelial cells, including proliferation, migration, extension and tubule formation. Further experiments of dual luciferase assays verified microRNA-16 directly targeting Bmi 1. microRNA-16 down-regulated the expression of vascular endothelial growth factor VEGF-A and VEGF- C which were closely related to the angiogenesis of GBM. Moreover, less vascular formed in the section of neoplasm of the microRNA- transduced group than the control group in vivo. CONCLUSIONS: Collectively, these findings indicate that loss of microRNA-16 may favor glioma angiogenesis, on the contrary overexpression of microRNA-16 in GBM cells plays a critical role in repressing endothelial function and angiogenesis by targeting Bmi-1. microRNA-16 may be a potential therapeutic agent in the treatment of GBM. PMID- 26373394 TI - Expeditious Entry to Functionalized Pseudo-peptidic Organoselenide Redox Modulators via Sequential Ugi/SN Methodology. AB - An efficient route towards the synthesis of symmetrical diselenide and seleniumcontaining quinone pseudopeptides via one-pot Ugi and sequential nucleophilic substitution (SN) methodology was developed. Compounds were evaluated for their antimicrobial and anticancer activities and their corresponding antioxidant/pro-oxidant profiles were assesed employing 2,2 diphenyl-1-picrylhydrazyl (DPPH), bleomycin dependent DNA damage and glutathione peroxidase (GPx)-like activity assays. Selenium based quinones were among the most potent cytotoxic compounds with a slight preference for MCF-7 compared to HepG2 cells and good free radical scavenging activity. Furthermore, symmetrical diselenides exhibited the most potent GPx-like activity compared to ebselen. Moreover, compounds 7, 8, 9 and 10 exhibited similar antifungal activity to the antifungal drug clotrimazole with modest activity against the Gram-positive bacterium S. aureus. These results indicate that some of the synthesized organoselenides are redox modulating agent with promising anti-cancer and antifungal potentials. PMID- 26373395 TI - Recent Advances in Anticancer Chemotherapeutics based upon Azepine Scaffold. AB - In the recent few years, the emergence of heterocyclic ring-containing anti cancer agents has gained a great deal of attention among medicinal chemists. Among these, azepine-based compounds are particularly becoming attractive recently. In this Focus Review, we highlight the recent advancements in the development of azepine-based anti-cancer compounds since the year 2000. PMID- 26373396 TI - Herpes labialis and Nigerian dental health care providers: knowledge, attitudes, behaviors, and refusal to treat. AB - BACKGROUND: The few existing studies on herpes labialis among health care workers have been predominantly among non-dental health care workers. The purpose of this study was to determine Nigerian dental health care providers' knowledge of, attitudes toward, preventive behaviors for, and refusal to treat patients with herpes labialis. METHODS: This cross-sectional study was conducted among final year dental students at the University of Benin, dental house officers, and residents at the University of Benin Teaching Hospital, Benin City, Nigeria. Data collection was via a self-administered questionnaire. Bivariate statistics and logistic regression were used to relate the dependent and independent variables. RESULTS: Of the 120 questionnaires distributed, 110 were completed and returned, giving a 91.7% retrieval rate. However, 15 of the returned questionnaires were discarded because they were improperly completed, leaving a total of 95 questionnaires for final analysis in this study. The majority of participants were over 28 years old (54.7%), male (67.4%), unmarried (66.3%), and postgraduate dental health care providers (51.6%). Less than half (43.2%) of participants demonstrated adequate overall knowledge of herpes labialis. About one-tenth (10.5%) and more than three-quarters (87.4%) of participants reported a positive attitude and performance of adequate preventive behaviors, respectively. A total of 16.8% of participants reported a high tendency to refuse treatment to patients with herpes labialis. Although not statistically significant, young, unmarried, male undergraduate participants reported a greater likelihood to refuse treatment to herpes labialis patients. We found a statistically significant positive correlation between attitude and refusal to treat patients with herpes labialis. However, marital status and the attitude of participants toward these patients emerged as the determinants for refusal to treat patients with herpes labialis. CONCLUSIONS: Data from this study revealed a high level of inadequate knowledge, negative attitudes, and reasonably adequate preventive behaviors with respect to herpes labialis. One out of every six dental health care workers studied reported having refused to treat patients with herpes labialis. Unmarried dental health care providers and those with negative attitudes toward herpes labialis patients were more prone to refuse treatment to these patients. PMID- 26373397 TI - Defending a traditional practice in the modern era: The use of lumbar puncture in the investigation of subarachnoid haemorrhage. AB - INTRODUCTION: Acute severe headache is a common medical presentation, and a common area of diagnostic uncertainty. Subarachnoid haemorrhage (SAH) is the cause in a minority of patients and has a high rate of morbidity and mortality. Therefore, its conclusive diagnosis with computed tomography (CT) or lumbar puncture (LP) is paramount. With advancement in imaging technology, emerging evidence now suggests that LP is no longer required for a subset of patients as CT has 100% sensitivity in detecting SAH, when performed under specific conditions. OBJECTIVES: To assess the proportion of patients with conclusive CSF xanthochromia results following a negative CT scan in suspected SAH to determine the diagnostic efficacy of LP. METHODS: CSF bilirubin and oxyhaemoglobin spectrophotometric absorbance data from all centres in a regional health board were identified for consecutive patients over a 6-month period. Results were stratified as conclusive (positive or negative), or inconclusive according to national guidelines. RESULTS: 239 of 255 (93.7%) results were conclusive: 89.0% were negative (227 of 255). 4.7% of results were positive (12 of 255), revealing 4 cerebral aneurysms requiring treatment. 16 out of 255 (6.3%) samples were inconclusive, yielding 1 aneurysm requiring treatment. In the same period, there were 27 CT-positive cases of SAH. CONCLUSIONS: LP has a high diagnostic yield, eliminating the need for neurosurgical opinion or investigation in almost 90% of cases. The test is both cost and time efficient and subjects only a small number of patients to the radiation and contrast risks of angiography. PMID- 26373398 TI - Body mass index in early and middle adult life: prospective associations with myocardial infarction, stroke and diabetes over a 30-year period: the British Regional Heart Study. AB - OBJECTIVES: Adiposity in middle age is an established risk factor for cardiovascular disease and type 2 diabetes; less is known about the impact of adiposity from early adult life. We examined the effects of high body mass index (BMI) in early and middle adulthood on myocardial infarction (MI), stroke and diabetes risks. DESIGN: A prospective cohort study. PARTICIPANTS: 7735 men with BMI measured in middle age (40-59 years) and BMI ascertained at 21 years from military records or participant recall. PRIMARY AND SECONDARY OUTCOME MEASURES: 30-year follow-up data for type 2 diabetes, MI and stroke incidence; Cox proportional hazards models were used to examine the effect of BMI at both ages on these outcomes, adjusted for age and smoking status. RESULTS: Among 4846 (63%) men (with complete data), a 1 kg/m(2) higher BMI at 21 years was associated with a 6% (95% CI 4% to 9%) higher type 2 diabetes risk, compared with a 21% (95% CI 18% to 24%) higher diabetes risk for a 1 kg/m(2) higher BMI in middle age (hazard ratio (HR) 1.21, 95% CI 1.18 to 1.24). Higher BMI in middle age was associated with a 6% (95% CI 4% to 8%) increase in MI and a 4% (95% CI 1% to 7%) increase in stroke; BMI at 21 years showed no associations with MI or stroke risk. CONCLUSIONS: Higher BMI at 21 years of age is associated with later diabetes incidence but not MI or stroke, while higher BMI in middle age is strongly associated with all outcomes. Early obesity prevention may reduce later type 2 diabetes risk, more than MI and stroke. PMID- 26373399 TI - Melanoma mortality following skin cancer screening in Germany. AB - OBJECTIVES: In 2003, a skin cancer screening campaign based on total body skin examination was launched in the federal state of Schleswig-Holstein, Germany. 20% of adults aged 20 and over were screened. In 2008, a 48% decline in melanoma mortality was reported. In the same year, skin screening was extended to the rest of Germany. We evaluated whether melanoma mortality trends decreased in Germany as compared with surrounding countries where skin screening is uncommon. We also evaluated whether the initial decreasing mortality trend observed in Schleswig Holstein was maintained with a longer follow-up. SETTING AND PARTICIPANTS: Regional and national melanoma mortality data from 1995 to 2013 were extracted from the GEKID database and the Federal Statistical Office. Mortality data for Germany and surrounding countries from 1980 to 2012 were extracted from the WHO mortality database. PRIMARY AND SECONDARY OUTCOME MEASURES: Age-adjusted (European Standard Population) mortality rates were computed and joinpoint analysis performed for Schleswig-Holstein, Germany and surrounding countries. RESULTS: In Schleswig-Holstein, melanoma mortality rates declined by 48% from 2003 to 2008, and from 2009 to 2013 returned to levels observed before screening initiation. During the 5 years of the national programme (2008-2012), melanoma mortality rates increased by 2.6% (95% CI -0.1 to 5.2) in men and 0.02% (95% CI 1.8 to 1.8) in women. No inflexion point in trends was identified after 2008 that could have suggested a decreasing melanoma mortality. Trends of cutaneous melanoma mortality in Germany from 1980 to 2012 did not differ from those observed in surrounding countries. CONCLUSIONS: The transient decrease mortality in Schleswig-Holstein followed by return to pre-screening levels could reflect a temporal modification in the reporting of death causes. An in-depth evaluation of the screening programme is required. PMID- 26373400 TI - Relationship between implementing interpersonal communication and mass education campaigns in emergency settings and use of reproductive healthcare services: evidence from Darfur, Sudan. AB - OBJECTIVES: (1) To examine changes in women's awareness and utilisation of reproductive healthcare services in emergency settings following provision of interpersonal communication (IPC) and mass education campaigns, and (2) to describe factors associated with reproductive healthcare service use in internally displaced person (IDP) camps. SETTING: Three camps containing 88 984 IDPs in Darfur, Sudan. PARTICIPANTS: 640 women aged 15-49 who had experienced pregnancy in the camp during the previous 2 years were enrolled in each of two independent cross-sectional surveys 26 months apart. INTERVENTIONS: IPC and mass education campaigns where community health workers disseminated information by home/shelter visits, clinic sessions, public meetings and other means to raise awareness and promote reproductive healthcare service use. PRIMARY OUTCOME MEASURES: Awareness of the existence of antenatal care (ANC) and tetanus toxoid (TT) vaccination services, reception of ANC and TT vaccination, place of delivery and use of postnatal care (PNC). RESULTS: The percentage of women who received home visits, and attended in-clinic sessions and public meetings increased from 61.6% to 86.7%, from 43.0% to 68.8%, and from 3.8% to 39.8%, respectively, between the initial and follow-up surveys. More women were aware of ANC (OR 18.6, 95% CI 13.1 to 26.5) and TT vaccination (OR 3.2, 95% CI 2.4 to 4.4) in the follow up than the initial survey, after multivariable adjustment. More women received >=3 ANC visits (OR 8.8, 95% CI 6.4 to 12.0) and >=3 doses of TT (OR 2.5, 95% CI 1.9 to 3.3), delivered at a healthcare facility (OR 5.4, 95% CI 4.0 to 7.4) and received a PNC visit (OR 5.5, 95% CI 4.0 to 7.7) in the follow-up than in the initial survey, after multivariable adjustment. CONCLUSIONS: Awareness about and utilisation of reproductive healthcare services were higher in the follow-up survey. An integrated IPC and mass education campaign is effective for improving women's reproductive health in emergency settings. PMID- 26373401 TI - Sick and still at school: an empirical study of sickness presence among students in Norwegian secondary school. AB - OBJECTIVES: This paper investigates sickness presence (SP) among students. The research questions asked are: What is the distribution of SP among students in Norwegian secondary school? What characterises students with high SP in Norwegian secondary schools? DESIGN: A cross-sectional survey conducted in 10th grade in lower secondary school (LSS) and level 2 in upper secondary school (USS). The study was conducted using multivariate binomial logistic regression analysis. PARTICIPANTS: The survey was administered to 66 schools, and 2 or 3 classes participated at each school. The response rate was 84% in LSS (n=1880) and 81% in USS (n=1160). PRIMARY AND SECONDARY OUTCOME MEASURES: The paper provides information about the distribution of SP in secondary schools. The paper also examines which factors influence high SP. RESULTS: 75% of students in LSS and 80% of students in USS reported SP in the previous school year. 24% of students in LSS and 33% of students in USS reported high SP (4 episodes or more). Students with high absence from school were more likely to report high SP (ORLSS=1.7, ORUSS=2.0) than those with low/no absence. Girls were more likely to report high SP (ORLSS=1.5, ORUSS=1.5) than boys. In LSS, students with high school motivation reported high SP more often than students with low/medium motivation. In USS, students in vocational studies programmes reported high SP more often than students in general/academic studies programmes. CONCLUSIONS: Some SP during a school year may be more common than no SP. Gender, absence, motivation and education programme were important factors for high SP in secondary school. PMID- 26373403 TI - Hypertension prevalence, incidence and risk factors among children and adolescents in Africa: a systematic review and meta-analysis protocol. AB - INTRODUCTION: The African adult population is facing a growing epidemic of hypertension. Establishment of accurate epidemiological data on hypertension in African children and adolescents may have important implications for hypertension preventive strategies in Africa. METHODS AND ANALYSIS: This systematic review and meta-analysis will follow the MOOSE Guidelines. Relevant abstracts published in English/French from 1 January 1985 to 31 July 2015 will be searched in PubMed, Google Scholar and Online African journals. Full texts of eligible studies will then be accessed through PubMed, Google Scholar, HINARI and the respective journals' websites. Relevant unpublished papers and conference proceedings will also be checked. Data will be analysed using R statistical software. The study specific estimates will be pooled through a random-effects meta-analysis model to obtain an overall summary estimate of the prevalence/incidence of hypertension across studies. Also, we will assess the association between risk factors and hypertension. Heterogeneity of studies will be evaluated by the chi(2) test on Cochrane's Q statistic. Funnel plots analysis and Egger's test will be done to detect publication bias. Results will be presented by geographic region (central, eastern, northern, southern and western Africa). A p value less than 0.05 will be considered significant for factors that predicted hypertension. ETHICS AND DISSEMINATION: The current study is based on published data, and thus ethical approval is not required. This systematic review and meta-analysis is expected to serve as input for designing early life preventive and control strategies, and as a guide for future research based on existing gaps. The final report of the systematic review in the form of a scientific paper will be published in peer reviewed journals. Findings will further be presented at conferences and submitted to relevant health authorities. TRIAL REGISTRATION NUMBER: CRD42015019029. PMID- 26373402 TI - Systematic review of the measurement properties of self-report physical activity questionnaires in healthy adult populations. AB - OBJECTIVE: This systematic review evaluated the measurement properties of current self-report physical activity questionnaires (SRPAQs) completed within healthy adult populations. DESIGN: Two reviewers independently searched seven electronic databases and hand searched for articles investigating measurement properties of a SRPAQ evaluating physical activity over the previous 6 months. Articles published from 1 May 2001 to 4 December 2014 were systematically screened and eligible studies were not limited to English language sources. Articles investigating specific race, gender or socioeconomic populations were excluded. RESULTS: 10 studies investigating 10 SRPAQs were included. The methodological quality of the included studies was evaluated using COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) and ranged from 'poor' to 'good'. The Recent Physical Activity Questionnaire, International Physical Activity Questionnaires and Physical Activity Assessment Tool demonstrated good/excellent test-retest reliability (intra-class coefficient (ICC)=0.76, p<0.0001; r=0.627-0.91; r=0.618, p<0.001, respectively), but variable criterion validity (r=0.67, p<0.0001; r=-0.02-0.43; r=0.392, p<0.01, respectively). The single-item measure showed significant criterion validity against an accelerometer (for moderate to vigorous physical activity (MVPA) k=0.23, 95% CI 0.05 to 0.41; and physical activity >=10 min bouts 0.39 (95% CI 0.14 to 0.64). Construct validity of the six-point scale and Human Activity Profile varied significantly with age, marital status and presence of comorbidities (p<0.05, <0.01, <0.000 and p<0.05, <0.05, <0.000, respectively). The 1 week Godlin Shephard recall demonstrated 'moderate' validity with the gold standard measure of accelerometry (r=0.43). CONCLUSIONS: Inconclusive evidence exists. Further investigation of criterion validity of the short-form International Physical Activity Questionnaire is required, as it demonstrated excellent test-retest reliability. PROSPERO NUMBER: CRD42012002484. PMID- 26373404 TI - Individual patient data meta-analysis of self-monitoring of blood pressure (BP SMART): a protocol. AB - INTRODUCTION: Self-monitoring of blood pressure is effective in reducing blood pressure in hypertension. However previous meta-analyses have shown a considerable amount of heterogeneity between studies, only part of which can be accounted for by meta-regression. This may be due to differences in design, recruited populations, intervention components or results among patient subgroups. To further investigate these differences, an individual patient data (IPD) meta-analysis of self-monitoring of blood pressure will be performed. METHODS AND ANALYSIS: We will identify randomised trials that have compared patients with hypertension who are self-monitoring blood pressure with those who are not and invite trialists to provide IPD including clinic and/or ambulatory systolic and diastolic blood pressure at baseline and all follow-up points where both intervention and control groups were measured. Other data requested will include measurement methodology, length of follow-up, cointerventions, baseline demographic (age, gender) and psychosocial factors (deprivation, quality of life), setting, intensity of self-monitoring, self-monitored blood pressure, comorbidities, lifestyle factors (weight, smoking) and presence or not of antihypertensive treatment. Data on all available patients will be included in order to take an intention-to-treat approach. A two-stage procedure for IPD meta analysis, stratified by trial and taking into account age, sex, diabetes and baseline systolic BP will be used. Exploratory subgroup analyses will further investigate non-linear relationships between the prespecified variables. Sensitivity analyses will assess the impact of trials which have and have not provided IPD. ETHICS AND DISSEMINATION: This study does not include identifiable data. Results will be disseminated in a peer-reviewed publication and by international conference presentations. CONCLUSIONS: IPD analysis should help the understanding of which self-monitoring interventions for which patient groups are most effective in the control of blood pressure. PMID- 26373406 TI - The CHICO (Children's Cough) Trial protocol: a feasibility randomised controlled trial investigating the clinical and cost-effectiveness of a complex intervention to improve the management of children presenting to primary care with acute respiratory tract infection. AB - INTRODUCTION: While most respiratory tract infections (RTIs) will resolve without treatment, many children will receive antibiotics and some will develop severe symptoms requiring hospitalisation. There have been calls for evidence to reduce uncertainty regarding the identification of children who will and will not benefit from antibiotics. The aim of this feasibility trial is to test recruitment and the acceptance of a complex behavioural intervention designed to reduce antibiotic prescribing, and to inform how best to conduct a larger trial. METHODS AND ANALYSIS: The CHICO (Children's Cough) trial is a single-centre feasibility cluster randomised controlled trial (RCT) comparing a web-based, within-consultation, behavioural intervention with usual care for children presenting to general practitioner practices with RTI and acute cough. The trial aims to recruit at least 300 children between October 2014 and April 2015, in a single area in South West England. Following informed consent, demographic information will be recorded, and symptoms and signs measured. Parents/carers of recruited children will be followed up on a weekly basis to establish symptom duration, resource use and cost of the illness to the parent until the child's cough has resolved or up to 8 weeks, whichever occurs earlier. A review of medical notes, including clinical history, primary care reconsultations and hospitalisations will be undertaken 2 months after recruitment. The trial feasibility will be assessed by: determining acceptability of the intervention to clinicians and parent/carers; quantifying differential recruitment and follow-up; determining intervention fidelity; the success in gathering the data necessary to conduct a cost-effectiveness analysis; and collecting data about antibiotic prescribing rates to inform the sample size needed for a fully powered RCT. ETHICS AND DISSEMINATION: The study was approved by the North West-Haydock Research Ethics Committee, UK (reference number: 14/NW/1034). The findings from this feasibility trial will be disseminated through research conferences and peer reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN23547970. PMID- 26373405 TI - Gender differences between WOMAC index scores, health-related quality of life and physical performance in an elderly Taiwanese population with knee osteoarthritis. AB - OBJECTIVE: To investigate the importance of the WOMAC index score, health-related quality of life and physical performance in each domain affected by knee osteoarthritis (OA) and to identify gender differences in the importance of these domains and physical performances. MATERIAL AND METHODS: We performed a population-based study for radiographic knee OA among participants aged more than 65 years. Demographic data were collected and anthropometric measurement, radiographic assessment, the WOMAC index score, the short-form 12 (SF-12), the Timed and Up to Go Test (TUGT) and the Five Times Sit to Stand Test (FTSST) were performed. RESULT: There were 901 individuals (409 males and 492 females) aged 74.04+/-6.92 (male: 76.35+/-7.33; female: 72.12+/-5.92) years included in this study. The WOMAC scores of participants with OA were higher than those without OA in males and females (male: 11.97+/-15.79 vs 8.23+/-12.84, p<0.001; female: 10.61+/-14.97 vs 7.59+/-3.31, p=0.032). The physical component summary (PCS) score was only significant in females with knee OA (62.14+/-24.66 vs 66.59+/ 23.85, p=0.043), while the mental component summary (MCS) score was only significant in males with knee OA (78.02+/-18.59 vs 81.98+/-15.46, p=0.02). The TUGT and FTSST were not significant in individuals with and without OA in males and females. Moreover, the multivariate results for the WOMAC score were significant for females (3.928 (95% CI 1.287 to 6.569), p=0.004). CONCLUSIONS: The PCS domains of SF-12 and MCS domains of SF-12 are crucial in Taiwanese females and elderly males, respectively, with knee OA. Different evaluation and treatment strategies based on gender differences should be considered in elderly Taiwanese patients with knee OA to improve their quality of life. PMID- 26373407 TI - Fluoride-ion-conducting Polymers: Ionic Conductivity and Fluoride Ion Diffusion Coefficient in Quaternized Polysulfones. AB - We describe the three-step synthesis of a new polymeric fluoride ion conductor based on the fully aromatic polymer polysulfone (PSU). In the first step, PSU is chloromethylated (CM-PSU) using reagents (i.e., stannic chloride, paraformaldehyde, and trimethylchlorosilane) that are less toxic than those used in the standard procedure. In the second step, CM-PSU reacts with a tertiary amine (trimethylamine or 1,4-diazabicyclo[2.2.2]octane) to form quaternary ammonium groups fixed on the PSU backbone and mobile chloride counter-anions. The chloride ions can, in a third step, be exchanged with fluoride ions by immersion of the ionomer in NaF solution. The fluoride ion conductivity reaches 3-5 mS cm( 1) at 25 degrees C and 5-10 mS cm(-1) at 40 degrees C. We determined the F(-) diffusion coefficient in these ionomers by pulsed gradient spin-echo (PGSE) high resolution magic angle spinning (HRMAS) nuclear magnetic resonance (NMR) spectroscopy and by impedance spectroscopy using the Nernst-Einstein relation. The diffusion coefficients determined by the two methods are in good agreement, ranging from 2 to 4*10(-10) m(2) s(-1) . The porosity and tortuosity of the ionomer membranes can be estimated. PMID- 26373408 TI - Factors associated with early growth in Egyptian infants: implications for addressing the dual burden of malnutrition. AB - Optimal nutrition is critical to the attainment of healthy growth, human capital and sustainable development. In Egypt, infants and young children face overlapping forms of malnutrition, including micronutrient deficiencies, stunting and overweight. Yet, in this setting, little is known about the factors associated with growth during the first year of life. A rise in stunting in Lower Egypt from 2005 to 2008 prompted this implementation research study, which followed a longitudinal cohort of infants from birth to 1 year of age within the context of a USAID-funded maternal and child health integrated programme. We sought to determine if growth patterns and factors related to early growth differed in Lower and Upper Egypt, and examined the relationship between weight loss and subsequent stunting at 12 months of age. Growth patterns revealed that length-for-age z-score (LAZ) decreased and weight-for-length z-score (WLZ) increased from 6 to 12 months of age in both regions. One-quarter of infants were stunted and nearly one-third were overweight by 12 months of age in lower Egypt. Minimum dietary diversity was significantly associated with WLZ in Lower Egypt (beta = 0.22, P < 0.05), but not in Upper Egypt. Diarrhoea, fever and programme exposure were not associated with any growth outcome. Weight loss during any period was associated with a twofold likelihood of stunting at 12 months in Lower Egypt, but not Upper Egypt. In countries, like Egypt, facing the nutrition transition, infant and young child nutrition programmes need to address both stunting and overweight through improving dietary quality and reducing reliance on energy-dense foods. PMID- 26373410 TI - Theoretical Models of Generalized Quasispecies. AB - Theoretical modeling of quasispecies has progressed in several directions. In this chapter, we review the works of Emmanuel Tannenbaum, who, together with Eugene Shakhnovich at Harvard University and later with colleagues and students at Ben-Gurion University in Beersheva, implemented one of the more useful approaches, by progressively setting up various formulations for the quasispecies model and solving them analytically. Our review will focus on these papers that have explored new models, assumed the relevant mathematical approximations, and proceeded to analytically solve for the steady-state solutions and run stochastic simulations . When applicable, these models were related to real-life problems and situations, including changing environments, presence of chemical mutagens, evolution of cancer and tumor cells , mutations in Escherichia coli, stem cells , chromosomal instability (CIN), propagation of antibiotic drug resistance , dynamics of bacteria with plasmids , DNA proofreading mechanisms, and more. PMID- 26373409 TI - A methodology for exploring biomarker--phenotype associations: application to flow cytometry data and systemic sclerosis clinical manifestations. AB - BACKGROUND: This work seeks to develop a methodology for identifying reliable biomarkers of disease activity, progression and outcome through the identification of significant associations between high-throughput flow cytometry (FC) data and interstitial lung disease (ILD) - a systemic sclerosis (SSc, or scleroderma) clinical phenotype which is the leading cause of morbidity and mortality in SSc. A specific aim of the work involves developing a clinically useful screening tool that could yield accurate assessments of disease state such as the risk or presence of SSc-ILD, the activity of lung involvement and the likelihood to respond to therapeutic intervention. Ultimately this instrument could facilitate a refined stratification of SSc patients into clinically relevant subsets at the time of diagnosis and subsequently during the course of the disease and thus help in preventing bad outcomes from disease progression or unnecessary treatment side effects. The methods utilized in the work involve: (1) clinical and peripheral blood flow cytometry data (Immune Response In Scleroderma, IRIS) from consented patients followed at the Johns Hopkins Scleroderma Center. (2) machine learning (Conditional Random Forests - CRF) coupled with Gene Set Enrichment Analysis (GSEA) to identify subsets of FC variables that are highly effective in classifying ILD patients; and (3) stochastic simulation to design, train and validate ILD risk screening tools. RESULTS: Our hybrid analysis approach (CRF-GSEA) proved successful in predicting SSc patient ILD status with a high degree of success (>82% correct classification in validation; 79 patients in the training data set, 40 patients in the validation data set). CONCLUSIONS: IRIS flow cytometry data provides useful information in assessing the ILD status of SSc patients. Our new approach combining Conditional Random Forests and Gene Set Enrichment Analysis was successful in identifying a subset of flow cytometry variables to create a screening tool that proved effective in correctly identifying ILD patients in the training and validation data sets. From a somewhat broader perspective, the identification of subsets of flow cytometry variables that exhibit coordinated movement (i.e., multi-variable up or down regulation) may lead to insights into possible effector pathways and thereby improve the state of knowledge of systemic sclerosis pathogenesis. PMID- 26373411 TI - Ductal Carcinoma In Situ: Treatment Update and Current Trends. AB - Ductal carcinoma in situ (DCIS) traditionally has been managed through various combinations of surgery, radiation, and endocrine therapy. However, concern for under- or over-treatment of DCIS has led many surgeons to question historically standardized approaches and instead begin to tailor treatment based on individual prognostic indicators. Recent and ongoing clinical trials have investigated the potential for active surveillance in DCIS, the possibility of eliminating radiation therapy (RT), and ways in which adjuvant systemic therapy may be refined. This review will summarize the current trends in the treatment of DCIS, as well as highlight the most pertinent clinical trials that are shaping management today. PMID- 26373412 TI - Consolidative Radiation in DLBCL: Evidence-Based Recommendations. AB - Radiation therapy (RT) has been described as the most effective single agent in the treatment of lymphoma; however, contemporary lymphoma treatment rarely relies on single agents. In the modern era, the selection of appropriate patients for combined modality therapy has become increasingly complex over the last decade with the transition to immunochemotherapy, the emergence of functional imaging for response evaluation, and the improvement in conformal avoidance of normal tissues when delivering RT. Recent evidence demonstrates that selected patients with DLBCL have significantly better outcomes when RT is added to immunochemotherapy; however, there are important knowledge gaps regarding the use of functional imaging to facilitate treatment selection. This article will review the current evidence regarding the optimal use of combined modality therapy for DLBCL. PMID- 26373413 TI - Tachykinins Processing is Significantly Impaired in PC1 and PC2 Mutant Mouse Spinal Cord S9 Fractions. AB - Substance P (SP) play a central role in nociceptive transmission and it is an agonist of the Neurokinin-1 receptor located in the lamina I of the spinal cord. SP is a major proteolytic product of the protachykinin-1 primarily synthesized in neurons. Proprotein convertases (PCs) are extensively expressed in the central nervous system and specifically cleave at C-terminal of either a pair of basic amino acids, or a single basic residue. The proteolysis control of endogenous protachykinins has a profound impact on pain perception and the role of PCs remain unclear. The objective of this study was to decipher the role of PC1 and PC2 in the proteolysis surrogate protachykinins (i.e. Tachykinin 20-68 and Tachykinin 58-78) using cellular fractions of spinal cords from wild type (WT), PC1(-/+) and PC2(-/+) animals and mass spectrometry. Full-length Tachykinin 20-68 and Tachykinin 58-78 was incubated for 30 min in WT, PC1(-/+) and PC2(-/+) mouse spinal cord S9 fractions and specific C-terminal peptide fragments were identified and quantified by mass spectrometry. The results clearly demonstrate that both PC1 and PC2 mediate the formation of SP and Tachykinin 58-71, an important SP precursor, with over 50 % reduction of the rate of formation in mutant PC1 and PC2 mouse S9 spinal cord fractions. The results obtained revealed that PC1 and PC2 are involved in the C-terminal processing of protachykinin peptides and suggest a major role in the maturation of the protachykinin-1 protein. PMID- 26373414 TI - Anticholinergic Medication Use and Fractures in Postmenopausal Women: Findings from the Women's Health Initiative. AB - BACKGROUND: Anticholinergic medication use has been associated with several negative health outcomes in older adults, but little is known about its risk for fractures. OBJECTIVE: To examine the association between anticholinergic medication use and fracture outcomes in community-dwelling postmenopausal women. METHODS: Utilizing a prospective cohort design, we examined data collected from 137,408 women aged 50-79 years from the Women's Health Initiative observational study and clinical trials not reporting hip fracture at baseline. Medications with moderate or strong anticholinergic effects were identified directly from drug containers during in-person interviews. The main outcome was fractures (hip, lower arm/wrist and total fractures). We performed multivariable Cox proportional hazard survival modelling to assess the association between anticholinergic use and the risk of fractures. RESULTS: At baseline, 10.6% of the women were using an anticholinergic medication, of which antihistamines were the most common medication class (48.4%). The multivariable-adjusted hazard ratios for anticholinergic medication use were 1.08 (95% confidence interval [CI] 0.89-1.30) for hip fracture, 1.01 (95% CI 0.91-1.13) for lower arm/wrist fracture and 1.03 (95% CI 0.98-1.09) for total fractures. We observed no association according to subclass or count of anticholinergic medications, or trends between the duration of anticholinergic use and any of the fracture outcomes. CONCLUSION: Anticholinergic medication use was not associated with an increased risk of fractures among community-dwelling women. Future research should make efforts to capture over-the-counter medication use and the cumulative anticholinergic burden in relation to important health outcomes for older adults. PMID- 26373415 TI - Actinomadura jiaoheensis sp. nov. and Actinomadura sporangiiformans sp. nov., two novel actinomycetes isolated from muddy soil and emended description of the genus Actinomadura. AB - Two novel actinomycetes, designated strains NEAU-Jh1-3(T) and NEAU-Jh2-5(T), were isolated from muddy soil collected from a riverbank in Jiaohe, Jilin Province, north China. A polyphasic study was carried out to establish the taxonomic positions of these strains. The 16S rRNA gene sequence analysis showed that the two novel isolates exhibited 99.9 % 16S rRNA gene sequence similarity with each other and that they are closely related to Actinomadura viridis IFO 15238(T) (99.6, 99.6 %) and Actinomadura vinacea IFO 14688(T) (99.3, 99.3 %). Phylogenetic analysis based on the 16S rRNA gene sequences indicated that the two cultures clustered together and formed a cluster with A. viridis IFO 15238(T), A. vinacea IFO 14688(T) and Actinomadura rugatobispora IFO 14382(T). However, the DNA-DNA hybridization value between strains NEAU-Jh1-3(T) and NEAU-Jh2-5(T) was 63.6 %, and the values between the two strains and their close phylogenetic relatives were also below 70 %. With reference to phenotypic characteristics, phylogenetic data and DNA-DNA hybridization results, the two strains can be distinguished from each other and their close phylogenetic relatives. Thus, strains NEAU-Jh1-3(T) and NEAU-Jh2-5(T) represent two novel species of the genus Actinomadura, for which the names Actinomadura jiaoheensis sp. nov. and Actinomadura sporangiiformans sp. nov. are proposed. The type strains are NEAU-Jh1-3(T) (=CGMCC 4.7197(T) = JCM 30341(T)) and NEAU-Jh2-5(T) (=CGMCC 4.7211(T) = JCM 30342(T)), respectively. PMID- 26373416 TI - Efficient biotransformation of ginsenoside Rb1 to Rd by isolated Aspergillus versicolor, excreting beta-glucosidase in the spore production phase of solid culture. AB - Ginsenosides are the major pharmacological components in ginseng. Microorganisms from a ginseng field were isolated to identify transformation of ginsenosides. Based on HPLC and LC-MS analysis, strain LFJ1403 showed strong activities to transform ginsenoside Rb1 to Rd as the sole product. Phylogenetic analysis of 18S rDNA indicated that LFJ1403 belonged to Aspergillus versicolor. Through comparing four systems of transforming Rb1 to Rd, strain LFJ1403 was found to secrete ginsenoside-converting enzymes in the spore production phase of plate culture. This result suggested that the enzyme could be directly obtained from the plate. The spore suspension, which contained the exocrine enzyme, was easy to prepare and efficient for biotransformation of ginsenoside Rb1 to Rd. Further study showed that the maximum bioconversion rate was 96% (w/w) in shake flasks when a spore suspension system was used with optimized biotransformation conditions. Scale-up of this system to 2L resulted in an 85% conversion rate. The ginsenoside Rb1 converting enzyme was separated by gradient HPLC with Q-Sepharose column, and its beta-glucosidase activity and Rb1-converting ability was assayed by the 4 Nitrophenyl-beta-D-glucopyranoside (PNPG) method and HPLC with C18 column, respectively. We obtained 130 U ml(-1) enzymatic activity with the purified beta glucosidase. This is the first report on efficiently converting ginsenoside using extracellular enzyme directly from the fungus spore production phase of solid culture. PMID- 26373417 TI - Cellulosimicrobium aquatile sp. nov., isolated from Panagal reservoir, Nalgonda, India. AB - A Gram-stain positive, non-spore forming, non-motile, yellow-pigmented, rod shaped and coccoid aerobic strain designated 3bp(T) was isolated from Panagal reservoir, at Nalgonda, Telangana, India. Based on 16S rRNA gene sequence analysis it was identified that strain 3bp(T) belongs to the class Actinobacteria and is closely related to Cellulosimicrobium funkei VTT E-072700(T), Cellulosimicrobium cellulans LMG16221(T) and Cellulosimicrobium terreum KCTC 19206(T). The DNA-DNA relatedness data demonstrated that strain 3bp(T) is distinguishable from the above three species of the genus. Further, the chemotaxonomic properties of strain 3bp(T) were consistent with those of the genus Cellulosimicrobium: MK-9(H4) was the predominant menaquinone, anteiso-C15 : 0, iso-C15:0, anteiso-C17 : 0 and iso- C16:0 were the predominant cellular fatty acids and the cell-wall peptidoglycan contains L-lysine. The DNA G+C content of strain 3bp(T) was 73.8 mol%. The results of the polyphasic analysis allowed a clear differentiation of strain 3bp(T) from all other members of the genus Cellulosimicrobium. Strain 3bp(T) is thus considered to represent a novel member of the genus Cellulosimicrobium, for which the name Cellulosimicrobium aquatile sp. nov. is proposed. The type strain is 3bp(T) (=KCTC 39527(T) = MCC 2761(T) = LMG 28646(T)). PMID- 26373418 TI - The Role of Community Education in Increasing Knowledge of Breast Health and Cancer: Findings from the Asian Breast Cancer Project in Boston, Massachusetts. AB - In the past decade, cancer rates have significantly decreased in the USA, but breast cancer survival is lower in Asian American women, likely due to lower rates of screening behaviors in Asian Americans compared to other ethnicities, which could lead to later stage cancer diagnosis and increased mortality. This paper reports on the Asian Breast Cancer (ABC) Project, a three-phase peer-led community program designed to promote cancer prevention by improving breast cancer screening rates among Chinese and Vietnamese women in the Greater Boston area. The three phases of planning and coalition building, community health worker training, and the community workshop intervention are described. The workshop intervention was evaluated by comparing pre- and post-workshop questionnaires evaluating knowledge about breast cancer screening and prevention. Two hundred fifty-two women participated in the program across 14 workshops. Each participant completed questionnaires about demographics, access to health care, and a five-item self-administered questionnaire about breast cancer knowledge. Results showed that the majority of the women had received a clinical breast exam or mammogram in the past 12 months (69 and 59 %, respectively), and older women were more likely to get a mammogram (85 %) or clinical breast exams (74 %) compared to younger women. Eighty-one percent of women were interested in reminder systems. Baseline knowledge was high for three survey questions about mammograms and breast cancer risk (88-97 %). For questions with fewer correct answers at baseline, knowledge about the meaning of lumps in the breast significantly increased (69 to 80 % correct, p < 0.0001), as well as knowledge about frequency of clinical breast exam (48 to 67 % correct, p < 0.0001). This pilot project indicated a partial effectiveness of the community workshop in a population with high baseline knowledge. The education workshop increased knowledge about breast lumps and clinical exam frequency. We also identified that reminder systems and appointment assistance are desired by this population. Our findings inform future cancer screening strategies for Asian Americans. PMID- 26373419 TI - Functional diversity of complex I subunits in Candida albicans mitochondria. AB - Our interest in the mitochondria of Candida albicans has progressed to the identification of several proteins that are critical to complex I (CI) activity. We speculated that there should be major functional differences at the protein level between mammalian and fungal mitochondria CI. In our pursuit of this idea, we were helped by published data of CI subunit proteins from a broad diversity of species that included two subunit proteins that are not found in mammals. These subunit proteins have been designated as Nuo1p and Nuo2p (NADH-ubiquinone oxidoreductases). Since functional assignments of both C. albicans proteins were unknown, other than having a putative NADH-oxidoreductase activity, we constructed knock-out strains that could be compared to parental cells. The relevance of our research relates to the critical roles of both proteins in cell biology and pathogenesis and their absence in mammals. These features suggest they may be exploited in antifungal drug discovery. Initially, we characterized Goa1p that apparently regulates CI activity but is not a CI subunit protein. We have used the goa1? for comparisons to Nuo1p and Nuo2p. We have demonstrated the critical role of these proteins in maintaining CI activities, virulence, and prolonging life span. More recently, transcriptional profiling of the three mutants and an ndh51? (protein is a highly conserved CI subunit) has revealed that there are overlapping yet also different functional assignments that suggest subunit specificity. The differences and similarities of each are described below along with our hypotheses to explain these data. Our conclusion and perspective is that the C. albicans CI subunit proteins are highly conserved except for two that define non-mammalian functions. PMID- 26373421 TI - Mass production of C50 carotenoids by Haloferax mediterranei in using extruded rice bran and starch under optimal conductivity of brined medium. AB - Microbial carotenoids have potentially healthcare or medical applications. Haloferax mediterranei was difficult to economically grow into a large quantities as well as producing a valuable pigment of carotenoids. This study reports a novel investigation into the optimal conductivity on the mass production of carotenoids from H. mediterranei. The major component at about 52.4% in the extracted red pigment has been confirmed as bacterioruberin, a C50 carotenoids, by liquid chromatography separation and mass spectrometry analysis. By maintaining higher conductivity of 40 S/m in the brined medium, the cell concentration attained to 7.73 * 10(9) cells/L with low pigments concentration of 125 mg/L. When the conductivity was controlled at about 30 S/m, we obtained the highest cell concentration to 1.29 * 10(10) cells/L with pigments of 361.4 mg/L. When the conductivity was maintained at optimal 25 S/m, the pigments can be increased to maximum value of 555.6 mg/L at lower cell concentration of 9.22 * 10(9) cells/L. But conductivity below 20 S/m will cause the significant decrease in cell concentration as well as pigments due to the osmotic stress around the cells. Red pigment of carotenoids from an extremely halophilic archaebacterium could be efficiently produced to a high concentration by applying optimal conductivity control in the brined medium with extruded low-cost rice bran and corn starch. PMID- 26373420 TI - A modified experimental model of malignant pleural disease induced by lung Lewis carcinoma (LLC) cells. AB - BACKGROUND: Malignant pleural effusion resulting mainly from pleural metastases of lung adenocarcinoma has clinical relevance, being a sign of poor prognosis and low life expectancy. Experimental models can mimic the human condition, contributing to advances in current understanding of the mechanisms patients' pleural fluid accumulation and possible therapeutic strategies. The objective of this study is to evaluate the role of different concentrations of Lewis lung carcinoma cells (LLC cells) at the time of induction of experimental MPE and the main effects on survival of animals. METHODS: C57BL/6 mice received intrapleural injection of 0.1, 0.5 or 1.5 * 10(5) LLC cells and survival curve, biochemical and pathological analyses of pleural fluid and tissue were analyzed. RESULTS: Evaluation of weight loss, mobility and survival showed that animals that received 0.5 * 10(5) cells maintained more stable condition up to day 14 and a gain of 6 days survival over mice that received the highest concentration. CONCLUSION: This study may allow a better understanding the mechanisms involved in the development of malignant pleural effusion and it may be promising in evaluating therapy to avoid recurrence, as the best time to indicate pleurodesis or target therapies. PMID- 26373422 TI - Horizontal stability of connective tissue grafts at the buccal aspect of single implants: a 1-year prospective case series. AB - AIM: To clinically evaluate the horizontal stability of a connective tissue graft (CTG) at the buccal aspect of single implants (1); to compare actual gingival thickness between thin and thick gingival biotype (2). MATERIALS AND METHODS: Periodontally healthy non-smoking patients with a single implant in the anterior maxilla (15-25) were selected for a prospective case series. All demonstrated a horizontal alveolar defect and were in need of contour augmentation by means of CTG for aesthetic reasons. Patients were enrolled 3 months after implant surgery and had been provided with a provisional screw-retained crown. CTG was inserted in the buccal mucosa via the envelope technique using one intrasulcular incision. An ultrasonic device was used to evaluate mucosal thickness (MT) at the buccal aspect. MT was assessed at t0 (before CTG), t1 (immediately after CTG), t2 (2 weeks after CTG = suture removal), t3 (3 months after CTG = permanent crown installation) and t4 (1 year after implant placement). The gingival biotype was categorized as thin or thick based on the transparency of a periodontal probe through the soft tissues while probing the buccal sulcus of the contra-lateral tooth. Gingival thickness (GT) was measured at the contra-lateral tooth using the same ultrasonic device. RESULTS: Thirty-seven patients (19 men, 18 women; mean age 38) met the selection criteria and consented to the treatment. Mean soft tissue gain immediately after CTG was on average 1.07 mm (SD 0.49). What remained of this tissue gain after 1 year was on average 0.97 mm (SD 0.48; 90.5%). Hence, mean soft tissue loss amounted to 0.10 mm (SD 0.23; 9.5%; p = 0.015) with no significant difference between patients with a thin or thick biotype (p >= 0.290). Patients with a thin biotype had a mean GT of 1.02 mm (SD 0.21), whereas GT was on average 1.32 mm (SD 0.31) in subjects with a thick biotype (p = 0.004). CONCLUSION: Connective tissue graft substantially thickens the peri-implant mucosa with acceptable stability over a 1-year period. PMID- 26373423 TI - Morphology, sex steroid level and gene expression analysis in gonadal sex reversal of triploid female (XXX) rainbow trout (Oncorhynchus mykiss). AB - In non-mammalian vertebrates, estrogens and expressions of cyp19a1 and foxl2 play critical roles in maintaining ovary differentiation and development, while dmrt1 and sox9 are male-specific genes in testicular differentiation and are highly conserved. In order to deeply understand the morphological change, sex steroids level and molecular mechanism of triploid female gonadal reversal in rainbow trout, we studied the ovary morphology, tendency of estradiol-17beta (E2) and testosterone (T) levels and the relative expressions of dmrt1, cyp19a1, sox9 and foxl2 in juvenile and adult fish. Our results demonstrated that the development of triploid female gonads in rainbow trout went through arrested development, oocytes dedifferentiation, ovary reconstruction and sex reversal finally. During early gonadal development (154-334 days post-fertilization), the expressions of foxl2 and cyp19a1 increased linearly, while expressions of dmrt1 and sox9 were extremely suppressed, and E2 level was higher, while T level was lower. During the mid-to-late period of triploid female gonadal development (574-964 days post fertilization), the expressions of dmrt1 and sox9 remained high and were very close to the quantity of diploid male genes, and T levels were even reaching diploid male plasma concentrations, while expressions of cyp19a1 and foxl2 were decreased, leading to decrease in E2 level. We realized that the development model of rainbow trout triploid female gonads was extremely rare, and the regulatory mechanism was very special. Genes involved in gonadal development and endogenous estrogens are pivotal factors in fish natural sex reversal. PMID- 26373425 TI - 1H, 15N and 13C backbone assignments of GDP-bound human H-Ras mutant G12V. AB - Harvey Ras (H-Ras) is a membrane-associated GTPase with critical functions in cell proliferation and differentiation. The G12V mutant of H-Ras is one of the most commonly encountered oncoproteins in human cancer. This mutation disrupts the GTPase activity of H-Ras, leading to constitutive activation and aberrant downstream signalling. Here we report the backbone resonance assignments of human H-Ras mutant G12V lacking the C-terminal membrane attachment domain. PMID- 26373424 TI - Trends in Inequalities in the Use of Condom by Urban Teenagers in Spain. AB - Social and economic inequalities in condom use by adolescents have been reported previously. Also, condom use has declined during the last decade. The aim of the study was to describe trends in the use of condoms in our setting, and how these trends may differ between socioeconomic groups in boys, and separately in girls, aged 17-19 years attending school in Barcelona between 2004 and 2012. We analyzed data from three annual surveys on risk factors in secondary students, which included a representative sample of the city's population; individuals who had previously had sexual intercourse (n = 1570) were included in the study. We calculated adjusted prevalence ratios (aPR) and their confidence intervals (95% CI) using robust Poisson regression models. The prevalence of condom use among boys was 87.0% in 2004 and 76.2% in 2012, and 76.7 and 64.7% among girls, respectively. This decrease was greater in adolescents with a low socioeconomic level, both in boys (aPR = 0.80) and girls (aPR = 0.84). The observed increase of socioeconomic inequalities in condom use in adolescents highlights a possible deterioration in good sexual practices and policies during the studied period. PMID- 26373426 TI - Chemical shift assignments for the Ig2 domain of human obscurin A. AB - The giant sarcomeric protein obscurin (~720 kDa) is an essential contributor to myofibrillogenesis and acts as the only known tether between the contractile apparatus and the surrounding membrane structures in myofibrils. Genomic characterization of OBSCN suggests a modular architecture, consisting of dozens of individually-folded Ig-like and FnIII-like domains arranged in tandem. Here we describe the sequence-specific chemical shift assignments of the second putative obscurin Ig-like domain (Ig2). This domain specifically binds to MyBP-C slow variant-1 through an unknown mechanism. Ultimately, the assignments presented here will facilitate high-resolution structure determination of Ig2 and provide insight into the specificity of the obscurin-MyBP-C interaction. PMID- 26373427 TI - Resonance assignment of DVU2108 that is part of the Orange Protein complex in Desulfovibrio vulgaris Hildenborough. AB - We report the 94 % assignment of DVU2108, a protein belonging to the Orange Protein family, that in Desulfovibrio vulgaris Hildenborough forms a protein complex named the Orange Protein complex. This complex has been shown to be implicated in the cell division of this organism. DVU2108 is a conserved protein in anaerobic microorganisms and in Desulfovibrio gigas the homologous protein was isolated with a novel Mo-Cu cluster non-covalently attached to the polypeptide chain. However, the heterologously produced DVU2108 did not contain any bound metal. These assignments provide the means to characterize the interaction of DVU2108 with the proteins that form the Orange Protein complex using NMR methods. PMID- 26373428 TI - 1H, 15N and 13C resonance assignments of light organ-associated fatty acid binding protein of Taiwanese fireflies. AB - Fatty acid-binding proteins (FABPs) are a family of proteins that modulate the transfer of various fatty acids in the cytosol and constitute a significant portion in many energy-consuming cells. The ligand binding properties and specific functions of a particular type of FABP seem to be diverse and depend on the respective binding cavity as well as the cell type from which this protein is derived. Previously, a novel FABP (lcFABP; lc: Luciola cerata) was identified in the light organ of Taiwanese fireflies. The lcFABP was proved to possess fatty acids binding capabilities, especially for fatty acids of length C14-C18. However, the structural details are unknown, and the structure-function relationship has remained to be further investigated. In this study, we finished the (1)H, (15)N and (13)C chemical shift assignments of (15)N/(13)C-enriched lcFABP by solution NMR spectroscopy. In addition, the secondary structure distribution was revealed based on the backbone N, H, Calpha, Halpha, C and side chain Cbeta assignments. These results can provide the basis for further structural exploration of lcFABP. PMID- 26373429 TI - NMR resonance assignments for the class II GTP binding RNA aptamer in complex with GTP. AB - The structures of RNA-aptamer-ligand complexes solved in the last two decades were instrumental in realizing the amazing potential of RNA for forming complex tertiary structures and for molecular recognition of small molecules. For GTP as ligand the sequences and secondary structures for multiple families of aptamers were reported which differ widely in their structural complexity, ligand affinity and ligand functional groups involved in RNA-binding. However, for only one of these families the structure of the GTP-RNA complex was solved. In order to gain further insights into the variability of ligand recognition modes we are currently determining the structure of another GTP-aptamer--the so-called class II aptamer--bound to GTP using NMR-spectroscopy in solution. As a prerequisite for a full structure determination, we report here (1)H, (13)C, (15)N and partial (31)P-NMR resonance assignments for the class II GTP-aptamer bound to GTP. PMID- 26373430 TI - Inhibition of AMPK through Lyn-Syk-Akt enhances FcepsilonRI signal pathways for allergic response. AB - AMPK was shown to negatively regulate FcepsilonRI activation, and FcepsilonR mediated Fyn activation can counteract the LKB1/AMPK axis in mast cells. However, the relationship between the major Src family kinase Lyn and AMPK remains poorly defined. Here, we investigate the molecular mechanism for AMPK inhibition by FcepsilonRI-Lyn signaling in rat RBL-2H3 cells. We found that FcepsilonRI activation could rapidly inhibit AMPK activation through increased AMPK phosphorylation at the inhibitory Ser485/491 residues without a change at the activating Th172 residue, and this was accompanied by a reduction of ACC phosphorylation. Using specific inhibitors and gene silencing, we found that such AMPK inhibition involved a signaling cascade through Lyn-Syk-Akt. When AMPK was activated by AICAR, A769662 and metformin, FcepsilonRI-mediated Syk, ERK, JNK and p38 activation, and TNFalpha release were all inhibited. Consistently, AMPK inhibition by compound C increased FcepsilonRI-mediated Lyn activation. Moreover, AMPK activation dominantly impaired IgE-induced recruitment of signal proteins to the FcepsilonRI by blocking the formation of FcepsilonRIbeta-Lyn-Syk, FcepsilonRIgamma-Lyn-Syk, and AMPK-FcepsilonRIbeta complexes. In vitro kinase assay further revealed the ability of AMPKalpha2 to phosphorylate FcepsilonRIbeta in the complex. In vivo, AMPK activation by metformin could readily reduce vascular permeability and ear swelling in a mouse model of passive cutaneous anaphylaxis mediated by IgE. In summary, our findings demonstrate that IgE mediated FcepsilonRI activation results in AMPK inhibition through activation of Lyn-Syk-Akt pathway, and as such FcepsilonRI receptor can efficiently propagate Lyn-mediated allergic signaling and response. These results provide important insights into the use of AMPK activators for the treatment of allergic diseases. KEY MESSAGES: AMPK is inhibited by FcepsilonRI via Lyn-Syk-Akt signaling in RBL 2H3 cells. AMPK inhibition supports FcepsilonRI-mediated Lyn signaling and allergic response. Metformin has inhibitory effect on passive cutaneous anaphylaxis. PMID- 26373431 TI - Diminished Resistance to Hyperoxia in Brains of Reproductively Senescent Female CBA/H Mice. AB - BACKGROUND We have explored sex differences in ability to maintain redox balance during acute oxidative stress in brains of mice. We aimed to determine if there were differences in oxidative/antioxidative status upon hyperoxia in brains of reproductively senescent CBA/H mice in order to elucidate some of the possible mechanisms of lifespan regulation. MATERIAL AND METHODS The brains of 12-month old male and female CBA/H mice (n=9 per sex and treatment) subjected to 18-h hyperoxia were evaluated for lipid peroxidation (LPO), antioxidative enzyme expression and activity - superoxide dismutase 1 and 2 (Sod-1, Sod-2), catalase (Cat), glutathione peroxidase 1 (Gpx-1), heme-oxygenase 1 (Ho-1), nad NF-E2 related factor 2 (Nrf2), and for 2-deoxy-2-[18F] fluoro-D-glucose (18FDG) uptake. RESULTS No increase in LPO was observed after hyperoxia, regardless of sex. Expression of Nrf-2 showed significant downregulation in hyperoxia-treated males (p=0.001), and upregulation in hyperoxia-treated females (p=0.023). Also, in females hyperoxia upregulated Sod-1 (p=0.046), and Ho-1 (p=0.014) genes. SOD1 protein was upregulated in both sexes after hyperoxia (p=0.009 for males and p=0.011 for females). SOD2 protein was upregulated only in females (p=0.008) while CAT (p=0.026) and HO-1 (p=0.042) proteins were increased after hyperoxia only in males. Uptake of 18FDG was decreased after hyperoxia in the back brain of females. CONCLUSIONS We found that females at their reproductive senescence are more susceptible to hyperoxia, compared to males. We propose this model of hyperoxia as a useful tool to assess sex differences in adaptive response to acute stress conditions, which may be partially responsible for observed sex differences in longevity of CBA/H mice. PMID- 26373432 TI - The natural history of Echinorhynchus bothniensis Zdzitowiecki and Valtonen, 1987 (Acanthocephala) in a high Arctic lake. AB - The acanthocephalan Echinorhynchus bothniensis Zdzitowiecki and Valtonen, 1987 differs from most other species in the genus Echinorhynchus Zoega in Muller, 1776 by infecting mysids (order Mysida) instead of amphipods (order Amphipoda) as intermediate hosts. Here we report on the occurrence of E. bothniensis in mysids (Mysis segerstralei Audzijonyte et Vainola) and in its fish definitive hosts in a high Arctic lake. Out of 15 907 sampled mysids, 4.8% were infected with a mean intensity of 1.05 worms (range 1-5), although there was notable variation between samples taken in different years and sites. Larger mysids appear more likely to be infected. Of five fish species sampled, charr,Salvelinus alpinus (Linnaeus), and a benthic-feeding whitefish morph, Coregonus lavaretus (Linnaeus), were the most heavily infected (mean abundances of 80 and 15, respectively). The adult parasite population in fish exhibited a female-biased sex ratio (1.78 : 1). Although E. bothniensis is rather unique in infecting mysids, many aspects of its natural history mirror that of other acanthocephalan species. PMID- 26373434 TI - Rapid Method for the Determination of the Stable Oxygen Isotope Ratio of Water in Alcoholic Beverages. AB - This paper demonstrates the first successful application of an online pyrolysis technique for the direct determination of oxygen isotope ratios (delta(18)O) of water in alcoholic beverages. Similar water concentrations in each sample were achieved by adjustment with absolute ethyl alcohol, and then a fixed GC split ratio can be used. All of the organic ingredients were successfully separated from the analyte on a CP-PoraBond Q column and subsequently vented out, whereas water molecules were transferred into the reaction furnace and converted to CO. With the system presented, 15-30 MUL of raw sample was diluted and can be analyzed repeatedly; the analytical precision was better than 0.40/00 (n = 5) in all cases, and more than 50 injections can be made per day. No apparent memory effect was observed even if water samples were injected using the same syringe; a strong correlation (R(2) = 0.9998) was found between the water delta(18)O of measured sample and that of working standards. There was no significant difference (p > 0.05) between the mean delta(18)O value and that obtained by the traditional method (CO2-water equilibration/isotope ratio mass spectrometry) and the newly developed method in this study. The advantages of this new method are its rapidity and straightforwardness, and less test portion is required. PMID- 26373433 TI - DYRK1A overexpression enhances STAT activity and astrogliogenesis in a Down syndrome mouse model. AB - Down syndrome (DS) arises from triplication of genes on human chromosome 21 and is associated with anomalies in brain development such as reduced production of neurons and increased generation of astrocytes. Here, we show that differentiation of cortical progenitor cells into astrocytes is promoted by DYRK1A, a Ser/Thr kinase encoded on human chromosome 21. In the Ts1Cje mouse model of DS, increased dosage of DYRK1A augments the propensity of progenitors to differentiate into astrocytes. This tendency is associated with enhanced astrogliogenesis in the developing neocortex. We also find that overexpression of DYRK1A upregulates the activity of the astrogliogenic transcription factor STAT in wild-type progenitors. Ts1Cje progenitors exhibit elevated STAT activity, and depletion of DYRK1A in these cells reverses the deregulation of STAT. In sum, our findings indicate that potentiation of the DYRK1A-STAT pathway in progenitors contributes to aberrant astrogliogenesis in DS. PMID- 26373436 TI - Improvement in the Thermal Stability of Pyrophosphatase by Conjugation to Poly(N isopropylacrylamide): Application to the Polymerase Chain Reaction. AB - Polymerase chain reaction (PCR) is a powerful method for nucleic acid amplification. However, the PCR is inhibited in its yield due to its byproduct, pyrophosphate (PPi), a byproduct of the reaction; the yield is thereby limited. The conventional method for hydrolysis of PPi by pyrophosphatase (PPase) is not well adapted for operation at elevated temperatures over long times as required during the PCR. In this work, we reported a strategy to improve the PCR yield using a conjugate of the enzyme with the thermally responsive polymer poly(N isopropylacrylamide) (PNIPAM). Pyrophosphatase (PPase) was conjugated to PNIPAM site-specifically near the active center. As compared to the free enzyme, the optimum temperature of the conjugate was shown to increase from 45 to 60 degrees C. For the conjugate, about 77% enzyme activity was retained after incubation at 60 degrees C for 3 h, representing a 6.8-fold increase as compared to the unconjugated enzyme. For the PCR using the conjugate, the yield was 1.5-fold greater than using the unconjugated enzyme. As well as improving the yield of the PCR (and possibly other biological reactions) at elevated temperature, polymer conjugation may also provide a strategy to improve the heat resistance of proteins more generally. PMID- 26373437 TI - Relationship between sarcopenic obesity-related phenotypes and inflammatory markers in postmenopausal women. AB - Ageing is associated with changes in body composition that may result in sarcopenic obesity (SO). Interleukin-6 (IL-6) and C-reactive protein (CRP) are important inflammatory markers related to ageing. SO has been examined as an important public health problem, but its association with inflammatory markers has yet to be investigated. The aim of this study was to investigate the association between SO-related phenotypes and inflammatory markers in postmenopausal women. A total of 130 women (66.7 +/- 5.2 years) underwent body composition evaluation using dual-energy X-ray absorptiometry. Volunteers were classified according to a SO definition previously described in the literature. Waist circumference (WC) and handgrip strength (HG) were also measured. Blood samples were collected for CRP, tumour necrosis factor and IL-6 measurements. All the inflammatory markers were higher in SO individuals when compared to non-SO; however, only IL-6 reached statistical significance (median 3.34 versus 1.37 pg ml-1 ; P<0.05). Also, CRP was significantly correlated (P<0.01) with body mass index (rs = 0.34), fat mass (FM; rs = 0.25) and WC (rs = 0.33). Similarly, IL 6 levels were significantly correlated (P<0.05) to age (rs = 0.19), FM (rs = 0.19) and WC (rs = 0.17). HG was found to be significantly reduced among subjects with higher IL-6 levels (P = 0.02). In summary, the combination of reduced muscle mass and excess body fat (i.e. SO) is associated with elevated inflammatory markers in postmenopausal women. Moreover, CRP and IL-6 are associated with SO-related phenotypes in this population. PMID- 26373435 TI - Radiation-Induced Alteration of the Brain Proteome: Understanding the Role of the Sirtuin 2 Deacetylase in a Murine Model. AB - Whole brain radiotherapy (WBRT) produces unwanted sequelae, albeit via unknown mechanisms. A deacetylase expressed in the central nervous system, Sirtuin 2 (SIRT2), has been linked to neurodegeneration. Therefore, we sought to challenge the notion that a single disease pathway is responsible for radiation-induced brain injury in Sirt2 wild-type (WT) and knockout (KO) mice at the proteomic level. We utilized isobaric tag for relative and absolute quantitation to analyze brain homogenates from Sirt2 WT and KO mice with and without WBRT. Selected proteins were independently verified, followed by ingenuity pathway analysis. Canonical pathways for Huntington's, Parkinson's, and Alzheimer's were acutely affected by radiation within 72 h of treatment. Although loss of Sirt2 preferentially affected both Huntington's and Parkinson's pathways, WBRT most significantly affected Huntington's-related proteins in the absence of Sirt2. Identical protein expression patterns were identified in Mog following WBRT in both Sirt2 WT and KO mice, revealing a proteomic radiation signature; however, long-term radiation effects were found to be associated with altered levels of a small number of key neurodegeneration-related proteins, identified as Mapt, Mog, Snap25, and Dnm1. Together, these data demonstrate the principle that the presence of Sirt2 can have significant effects on the brain proteome and its response to ionizing radiation. PMID- 26373438 TI - Consumer participation in early detection of the deteriorating patient and call activation to rapid response systems: a literature review. AB - AIMS AND OBJECTIVES: This review investigated the impact of consumer participation in recognition of patient deterioration and response through call activation in rapid response systems. BACKGROUND: Nurses and doctors have taken the main role in recognition and response to patient deterioration through hospital rapid response systems. Yet patients and visitors (consumers) have appeared well placed to notice early signs of deterioration. In response, many hospitals have sought to partner health professionals with consumers in detection and response to early deterioration. However, to date, there have been no published research-based reviews to establish the impact of introducing consumer involvement into rapid response systems. DESIGN: A critical research-based review was undertaken. METHODS: A comprehensive search of databases from 2006-2014 identified 11 studies. Critical appraisal of these studies was undertaken and thematic analysis of the findings revealed four major themes. RESULTS: Following implementation of the consumer activation programmes, the number of calls made by the consumers following detection of deterioration increased. Interestingly, the number of staff calls also increased. Importantly, mortality numbers were found to decrease in one major study following the introduction of consumer call activation. Consumer and staff knowledge and satisfaction with the new programmes indicated mixed results. Initial concerns of the staff over consumer involvement overwhelming the rapid response systems did not eventuate. Evaluation of successful consumer-activated programmes indicated the importance of: effective staff education and training; ongoing consumer education by nurses and clear educational materials. CONCLUSIONS: Findings indicated positive patient outcomes following introduction of consumer call activation programmes within rapid response systems. Effective consumer programmes included information that was readily accessible, easy-to-understand and available in a range of multimedia materials accompanied by the explanation and support of health professionals. RELEVANCE TO CLINICAL PRACTICE: Introduction of consumer-activated programmes within rapid response systems appears likely to improve outcomes for patients experiencing deterioration. PMID- 26373439 TI - Role of Notch signaling during lipopolysaccharide-induced preterm labor. AB - Notch signaling pathways exert effects throughout pregnancy and are activated in response to TLR ligands. To investigate the role of Notch signaling in preterm labor, Notch receptors (Notch1-4), its ligand Delta-like protein-1, transcriptional repressor hairy and enhancer of split-1, and Notch deregulator Numb were assessed. Preterm labor was initiated on gestation d 14.5 by 1 of 2 methods: 1) inflammation-induced preterm labor: intrauterine injection of LPS (a TLR4 agonist) and 2) hormonally induced preterm labor: subcutaneous injection of mifepristone. Delta-like protein-1, Notch1, and hairy and enhancer of split-1 were elevated significantly, and Numb was decreased in the uterus and placenta of inflammation-induced preterm labor mice but remained unchanged in hormonally induced preterm labor compared with their respective controls. F4/80(+) macrophage polarization was skewed in the uterus of inflammation-induced preterm labor toward M1-positive (CD11c(+)) and double-positive [CD11c(+) (M1) and CD206(+) (M2)] cells. This process is dependent on activation of Notch signaling, as shown by suppression of M1 and M2 macrophage-associated cytokines in decidual macrophages in response to gamma-secretase inhibitor (an inhibitor of Notch receptor processing) treatment ex vivo. gamma-Secretase inhibitor treatment also diminished the LPS-induced secretion of proinflammatory cytokines and chemokines in decidual and placental cells cultured ex vivo. Furthermore, treatment with recombinant Delta-like protein-1 ligand enhanced the LPS-induced proinflammatory response. Notch ligands (Jagged 1 and 2 and Delta-like protein-4) and vascular endothelial growth factor and its receptor involved in angiogenesis were reduced significantly in the uterus and placenta during inflammation-induced preterm labor. These results suggest that up-regulation of Notch-related inflammation and down-regulation of angiogenesis factors may be associated with inflammation induced preterm labor but not with hormonally induced preterm labor. PMID- 26373441 TI - Genomic insights into the taxonomic status of the Bacillus cereus group. AB - The identification and phylogenetic relationships of bacteria within the Bacillus cereus group are controversial. This study aimed at determining the taxonomic affiliations of these strains using the whole-genome sequence-based Genome BLAST Distance Phylogeny (GBDP) approach. The GBDP analysis clearly separated 224 strains into 30 clusters, representing eleven known, partially merged species and accordingly 19-20 putative novel species. Additionally, 16S rRNA gene analysis, a novel variant of multi-locus sequence analysis (nMLSA) and screening of virulence genes were performed. The 16S rRNA gene sequence was not sufficient to differentiate the bacteria within this group due to its high conservation. The nMLSA results were consistent with GBDP. Moreover, a fast typing method was proposed using the pycA gene, and where necessary, the ccpA gene. The pXO plasmids and cry genes were widely distributed, suggesting little correlation with the phylogenetic positions of the host bacteria. This might explain why classifications based on virulence characteristics proved unsatisfactory in the past. In summary, this is the first large-scale and systematic study of the taxonomic status of the bacteria within the B. cereus group using whole-genome sequences, and is likely to contribute to further insights into their pathogenicity, phylogeny and adaptation to diverse environments. PMID- 26373442 TI - The RNA chaperone Hfq enables the environmental stress tolerance super-phenotype of Pseudomonas putida. AB - The natural physiological regime of the soil bacterium Pseudomonas putida involves incessant exposure to endogenous metabolic conflicts and environmental physicochemical insults. Yet, the role of assisted small RNA-mRNA pairing in the stress tolerance super-phenotype that is the trademark of this bacterium has not been accredited. We have thoroughly explored the physiological consequences -in particular those related to exogenous stress - of deleting the hfq gene of P. putida, which encodes the major RNA chaperone that promotes sRNA-target mRNA interactions. While the overall trend was a general weakening of every robustness descriptor of the Deltahfq strain, growth parameters and production of central metabolic enzymes were comparatively less affected than other qualities that depend directly on energy status (e.g. motility, DNA repair). The overall catalytic vigour of the mutant decreased to < 20% than the wild-type strain, as estimated from the specific growth rate of cells carrying the catabolic TOL plasmid pWW0 for m-xylene biodegradation. Several loss-of-function phenotypes could be traced to the effect of the Deltahfq deletion on the intracellular contents of the stationary sigma factor RpoS. It thus seems that Hfq, while not indispensable for any essential function, contributes to shape the environmental lifestyle of P. putida. PMID- 26373445 TI - The carboboration of Me3Si-substituted alkynes and allenes with boranes and borocations. AB - The 1,1-carboboration of 1-Me3Si-1-alkynes is the dominant reaction observed using [PhBCl(2-DMAP)][AlCl4], 1, and PhBCl2 electrophiles, with highly substituted vinyl pinacol boronate esters isolated post esterification. Other aryl and heteroaryl congeners of both 1 and PhBCl2 have a limited scope in the 1,1-carboboration of 1-Me3Si-1-alkynes, with desilylboration more prevalent. PhBCl2 converts Me3Si-substituted allenes to allylboranes via a formal 1,3 carboboration with Me3Si-migration. [Cl2B(2-DMAP)][AlCl4] reacts with a number of 1-Me3Si-1-alkynes by desilylboration, whilst with Me3Si-ethyne a 1,1 boroamination reaction proceeds, which with excess boron electrophile is followed by an intermolecular desilylboration to form a tricationic-borate. The use of excess 1-Me3Si-1-propyne relative to 1 (and a thienyl congener of 1) formed 2 boradienes in low yields from the reaction with two equivalents of alkyne. Vinyl borocations ligated by 2,6-lutidine of the general formula, [(vinyl)BCl(2,6 lutidine)][AlCl4] formed 1-boradienes with 1-Me3Si-1-alkynes. PMID- 26373443 TI - Characterization of the Transcriptional Complexity of the Receptive and Pre receptive Endometria of Dairy Goats. AB - Endometrium receptivity is essential for successful embryo implantation in mammals. However, the lack of genetic information remains an obstacle to understanding the mechanisms underlying the development of a receptive endometrium from the pre-receptive phase in dairy goats. In this study, more than 4 billion high-quality reads were generated and de novo assembled into 102,441 unigenes; these unigenes were annotated using published databases. A total of 3,255 unigenes that were differentially expressed (DEGs) between the PE and RE were discovered in this study (P-values < 0.05). In addition, 76,729-77,102 putative SNPs and 12,837 SSRs were discovered in this study. Bioinformatics analysis of the DEGs revealed a number of biological processes and pathways that are potentially involved in the establishment of the RE, notably including the GO terms proteolysis, apoptosis, and cell adhesion and the KEGG pathways Cell cycle and extracellular matrix (ECM)-receptor interaction. We speculated that ADCY8, VCAN, SPOCK1, THBS1, and THBS2 may play important roles in the development of endometrial receptivity. The de novo assembly provided a good starting point and will serve as a valuable resource for further investigations into endometrium receptivity in dairy goats and future studies on the genomes of goats and other related mammals. PMID- 26373451 TI - Breadth of tuning in taste afferent neurons varies with stimulus strength. AB - Gustatory stimuli are detected by taste buds and transmitted to the hindbrain via sensory afferent neurons. Whether each taste quality (sweet, bitter and so on) is encoded by separate neurons ('labelled lines') remains controversial. We used mice expressing GCaMP3 in geniculate ganglion sensory neurons to investigate taste-evoked activity. Using confocal calcium imaging, we recorded responses to oral stimulation with prototypic taste stimuli. Up to 69% of neurons respond to multiple tastants. Moreover, neurons tuned to a single taste quality at low concentration become more broadly tuned when stimuli are presented at higher concentration. Responses to sucrose and monosodium glutamate are most related. Although mice prefer dilute NaCl solutions and avoid concentrated NaCl, we found no evidence for two separate populations of sensory neurons that encode this distinction. Altogether, our data suggest that taste is encoded by activity in patterns of peripheral sensory neurons and challenge the notion of strict labelled line coding. PMID- 26373452 TI - Paenibacillus zeae sp. nov., isolated from maize (Zea mays L.) seeds. AB - Four Gram-stain-positive bacterial strains, designated 6R2T, 6R18, 3T2 and 3T10, isolated from seeds of hybrid maize (Zea mays L., Jingke 968) were investigated using a polyphasic taxonomic approach. Cells were aerobic, motile, spore-forming and rod-shaped. Phylogenetic analysis based on 16S rRNA gene sequences indicated that the isolates may represent a novel species of the genus Paenibacillus, the four closest neighbours being Paenibacillus lautus NRRL NRS-666T (97.1 % similarity), Paenibacillus glucanolyticus DSM 5162T (97.0 %), Paenibacillus lactis MB 1871T (97.0 %) and Paenibacillus chibensis JCM 9905T (96.8 %). The DNA G+C content of strain 6R2T was 51.8 mol%. Its polar lipid profile consisted of diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine. The predominant respiratory quinone was menaquinone 7 (MK-7) and the major fatty acids were anteiso-C15 : 0 and iso-C14 : 0. Strains 6R2T, 6R18, 3T2 and 3T10 were clearly distinguished from the above type strains using phylogenetic analysis, DNA-DNA hybridization, and a range of physiological and biochemical characteristics. It is evident from the genotypic and phenotypic data that strains 6R2T, 6R18, 3T2 and 3T10 represent a novel species of the genus Paenibacillus, for which the name Paenibacillus zeae sp. nov. is proposed. The type strain is 6R2T ( = KCTC 33674T = CICC 23860T). PMID- 26373453 TI - WRKY Transcription Factors Phosphorylated by MAPK Regulate a Plant Immune NADPH Oxidase in Nicotiana benthamiana. AB - Pathogen attack sequentially confers pattern-triggered immunity (PTI) and effector-triggered immunity (ETI) after sensing of pathogen patterns and effectors by plant immune receptors, respectively. Reactive oxygen species (ROS) play pivotal roles in PTI and ETI as signaling molecules. Nicotiana benthamiana RBOHB, an NADPH oxidase, is responsible for both the transient PTI ROS burst and the robust ETI ROS burst. Here, we show that RBOHB transactivation mediated by MAPK contributes to R3a/AVR3a-triggered ETI (AVR3a-ETI) ROS burst. RBOHB is markedly induced during the ETI and INF1-triggered PTI (INF1-PTI), but not flg22 tiggered PTI (flg22-PTI). We found that the RBOHB promoter contains a functional W-box in the R3a/AVR3a and INF1 signal-responsive cis-element. Ectopic expression of four phospho-mimicking mutants of WRKY transcription factors, which are MAPK substrates, induced RBOHB, and yeast one-hybrid analysis indicated that these mutants bind to the cis-element. Chromatin immunoprecipitation assays indicated direct binding of the WRKY to the cis-element in plants. Silencing of multiple WRKY genes compromised the upregulation of RBOHB, resulting in impairment of AVR3a-ETI and INF1-PTI ROS bursts, but not the flg22-PTI ROS burst. These results suggest that the MAPK-WRKY pathway is required for AVR3a-ETI and INF1-PTI ROS bursts by activation of RBOHB. PMID- 26373454 TI - Red Light-Mediated Degradation of CONSTANS by the E3 Ubiquitin Ligase HOS1 Regulates Photoperiodic Flowering in Arabidopsis. AB - The regulation of CONSTANS (CO) gene expression is crucial to accurately measure changes in daylength, which influences flowering time in Arabidopsis thaliana. CO expression is under both transcriptional and posttranslational control mechanisms. We previously showed that the E3 ubiquitin ligase HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENES1 (HOS1) physically interacts with CO in Arabidopsis. This interaction is required to precisely modulate the timing of CO accumulation and, consequently, to maintain low levels of FLOWERING LOCUS T expression during the first part of the day. The data presented here demonstrate that HOS1 is involved in the red light-mediated degradation of CO that takes place in the early stages of the daylight period. Our results show that phytochrome B (phyB) is able to regulate flowering time, acting in the phloem companion cells, as previously described for CO and HOS1. Moreover, we reveal that phyB physically interacts with HOS1 and CO, indicating that the three proteins may be present in a complex in planta that is required to coordinate a correct photoperiodic response in Arabidopsis. PMID- 26373455 TI - Genome-Wide Prediction and Validation of Intergenic Enhancers in Arabidopsis Using Open Chromatin Signatures. AB - Enhancers are important regulators of gene expression in eukaryotes. Enhancers function independently of their distance and orientation to the promoters of target genes. Thus, enhancers have been difficult to identify. Only a few enhancers, especially distant intergenic enhancers, have been identified in plants. We developed an enhancer prediction system based exclusively on the DNase I hypersensitive sites (DHSs) in the Arabidopsis thaliana genome. A set of 10,044 DHSs located in intergenic regions, which are away from any gene promoters, were predicted to be putative enhancers. We examined the functions of 14 predicted enhancers using the beta-glucuronidase gene reporter. Ten of the 14 (71%) candidates were validated by the reporter assay. We also designed 10 constructs using intergenic sequences that are not associated with DHSs, and none of these constructs showed enhancer activities in reporter assays. In addition, the tissue specificity of the putative enhancers can be precisely predicted based on DNase I hypersensitivity data sets developed from different plant tissues. These results suggest that the open chromatin signature-based enhancer prediction system developed in Arabidopsis may serve as a universal system for enhancer identification in plants. PMID- 26373457 TI - Epidermal necrosis with multinucleated keratinocytes: a possible diagnostic clue for dermatitis artefacta in children. PMID- 26373458 TI - X-ray Crystallography in Open-Framework Materials. AB - Open-framework materials, such as metal-organic frameworks (MOFs) and coordination polymers have been widely investigated for their gas adsorption and separation properties. However, recent studies have demonstrated that their highly crystalline structures can be used to periodically organize guest molecules and non-structural metal compounds either within their pore voids or by anchoring to their framework architecture. Accordingly, the open framework can act as a matrix for isolating and elucidating the structures of these moieties by X-ray diffraction. This concept has broad scope for development as an analytical tool where obtaining single crystals of a target molecule presents a significant challenge and it additionally offers potential for obtaining insights into chemically reactive species that can be stabilized within the pore network. However, the technique does have limitations and as yet a general experimental method has not been realized. Herein we focus on recent examples in which framework materials have been utilized as a scaffold for ordering molecules for analysis by diffraction methods and canvass areas for future exploration. PMID- 26373456 TI - Autophagy levels are elevated in barrett's esophagus and promote cell survival from acid and oxidative stress. AB - Autophagy is a highly conserved mechanism that is activated during cellular stress. We hypothesized that autophagy may be induced by acid reflux, which causes injury, and inflammation, and therefore, contributes to the pathogenesis of Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). Currently, the role of autophagy in BE and EAC is poorly studied. We quantitatively define autophagy levels in human BE cell lines, a transgenic mouse model of BE, and human BE, and EAC biopsies. Human non-dysplastic BE had the highest basal number of autophagic vesicles (AVs), while AVs were reduced in normal squamous cells and dysplastic BE cells, and nearly absent in EAC. To demonstrate a functional role for autophagy in BE pathogenesis, normal squamous (STR), non-dysplastic BE (CPA), dysplastic BE (CPD), and EAC (OE19) cell lines were exposed to an acid pulse (pH 3.5) followed by incubation in the presence or absence of chloroquine, an autophagy inhibitor. Acid exposure increased reactive oxygen species (ROS) levels in STR and CPA cells. Chloroquine alone had a small impact on intracellular ROS or cell survival. However, combination of chloroquine with the acid pulse resulted in a significant increase in ROS levels at 6 h in STR and CPA cells, and increased cell death in all cell lines. These findings establish increased numbers of AVs in human BE compared to normal squamous or EAC, and suggest that autophagy functions to improve cell survival after acid reflux injury. Autophagy may thus play a critical role in BE pathogenesis and progression. (c) 2015 Wiley Periodicals, Inc. PMID- 26373460 TI - Ageing in Rett syndrome. AB - BACKGROUND: The aim was to gain a UK national sample of people with Rett syndrome across the age range and (1) conduct a cross-sectional comparison of age groups and (2) undertake a longitudinal follow-up. METHODS: From 308 potential participants approached to take part, a sample of 91 girls and women was achieved (29.5%). Their ages ranged from 4 to 47 years, and 71 were known to have a mutation in the methyl-CpG binding protein-2 (MECP2) gene. Seventy-two of the initial sample were followed up 16 months later, and 50 returned completed assessments (69.4%). Their ages ranged from 7 to 48 years, and 42 were MECP2 positive. Parental questionnaire measures of Rett syndrome specific characteristics, impulsivity, overactivity, mood, interest and pleasure, repetitive behaviour and self-injury were administered. RESULTS: Adaptive behaviour and behavioural characteristics of Rett syndrome were similar across age groups and, where assessed, stable over time, as were repetitive behaviours generally and self-injury. There was some suggestion of deterioration in health arising with ageing, principally contributed to by deteriorations in dental and gastro-intestinal problems both with moderate effect sizes. Indicators of mood, interest and pleasure differed significantly across age groups. The total scale score significantly deteriorated over time, with a moderate effect size. CONCLUSIONS: This study provides further evidence for the post-regression stability that characterises Rett syndrome. Emergent low mood in Rett syndrome requires further research. PMID- 26373463 TI - 5-(Chloromethyl)furfural is the New HMF: Functionally Equivalent But More Practical in Terms of its Production From Biomass. AB - 5-(Chloromethyl)furfural (CMF) is a disruptive innovation in the biorefinery. Chemically, it is at least as versatile as the well-known HMF but, unlike HMF, it is accessible in high yield directly from cellulosic biomass due to its lipophilicity and stability under acidic conditions, which facilitate isolation. It has a rich derivative chemistry that includes biofuels, renewable polymers, specialty chemicals, and value-added agrochemical and pharmaceutical products. PMID- 26373461 TI - Dynamic correlations between hemodynamic, metabolic, and neuronal responses to acute whole-brain ischemia. AB - Cerebral ischemia sets off a cascade of neuronal and metabolic responses to preserve brain viability. An understanding of the temporal evolution of these changes during and after ischemia, and their correlation with hemodynamic changes, is essential. In this study, a 12-min whole-brain ischemia based on the four-blood-vessel occlusion model was employed in rats. Using a high-temporal resolution simultaneous (1)H-(31)P MRS acquisition sequence at 9.4 T, we investigated dynamic occlusion and reperfusion responses in cerebral lactate (Lac), phosphocreatine (PCr), adenosine triphosphate (ATP), pH, and blood oxygenation level dependence (BOLD), together with changes in neuronal field potential activity. We reveal tightly coupled dynamics between hemodynamic, metabolic, and neuronal responses to ischemia. Neuronal activity, BOLD, PCr, Lac, and pH changed immediately following occlusion, indicating reduced energy substrates and consumption, and increased glycolysis to maintain cellular ATP levels, which started to decrease 2.2 min after the onset of occlusion. ATP stores were then gradually consumed to maintain a minimum housekeeping neuronal activity level. By correlating dynamic changes of brain activity, BOLD, and energy metabolism, new insights into the brain's survival ability and mechanisms during an acute ischemic attack from the perspectives of cerebral metabolism, neuroenergetics, and neuronal activity were gained. PMID- 26373464 TI - Rethinking industrial citizenship: the role and meaning of work in an age of austerity. AB - T. H. Marshall in his famous tract Citizenship and Social Class wrote briefly about what he called 'industrial citizenship', a type of belonging rooted in the workplace. Here Marshall's ideas are developed alongside a consideration of Durkheim's Professional Ethics and Civic Morals together with research material from the Guinness Company. It shows the way the Company actively sought to create 'Guinness citizenship' within its London brewery. The article draws out the ways in which the significance and potential of work based citizenship for ameliorating the ills of industrial society are clearly articulated in mid twentieth century Britain and echo earlier neglected Durkheimian sociological ideas on work. These ideas have real potential to inform contemporary academic and policy debates about the nature of capitalism and the form and content of work now and in the future. PMID- 26373465 TI - Concise Review: Exciting Cells: Modeling Genetic Epilepsies with Patient-Derived Induced Pluripotent Stem Cells. AB - Human induced pluripotent stem cell (iPSC) models of epilepsy are becoming a revolutionary platform for mechanistic studies and drug discovery. The skyrocketing pace of epilepsy gene discovery is vastly outstripping the development of in vivo animal models. Currently, antiepileptic drug prescribing to patients with specific genetic epilepsies is based on small-scale clinical trials and empiricism; however, rapid production of patient-derived iPSC models will allow for precision therapy. We review iPSC-based studies that have already afforded novel discoveries in diseases with epileptic phenotypes, as well as challenges to using iPSC-based neurological disease models. We also discuss iPSC derived cardiomyocyte studies of arrhythmia-inducing ion channelopathies that exemplify novel drug discovery and use of multielectrode array technology that can be translated to epilepsy research. Beyond initial studies of Rett, Timothy, Phelan-McDermid, and Dravet syndromes, the stage is set for groundbreaking iPSC based mechanistic and therapeutic discoveries in genetic epilepsies with the potential to impact patient treatment and quality of life. PMID- 26373466 TI - Fracture of Jammed Colloidal Suspensions. AB - Concentrated colloidal suspensions display dramatic rises in viscosity, leading to jamming and granulation, with increasing shear rate. It has been proposed that these effects result from inter particle friction, as lubrication forces are overcome. This suggests the jamming of concentrated colloidal suspensions should exhibit some shared phenomenology with macroscopic granular systems where friction leads to two different types of jammed state. Here we show that transient rheological measurements can be used to probe the processes of granulation in concentrated colloidal suspensions. Our results support the idea that frictional contacts are created between jammed particles. The jamming behaviour displays two qualitatively different regimes separated by a critical strain rate with qualitatively different types of fracture/break up behaviour. In the lower strain rate regime, it is found that vibrations can be used to control jamming and granulation, resulting in a flowable fluid. PMID- 26373470 TI - Tinnitus: perspectives from human neuroimaging. AB - Tinnitus is the perception of phantom sound in the absence of a corresponding external source. It is a highly prevalent disorder, and most cases are caused by cochlear injury that leads to peripheral deafferentation, which results in adaptive changes in the CNS. In this article we critically assess the recent neuroimaging studies in individuals with tinnitus that suggest that the disorder is accompanied by functional and structural brain abnormalities in distributed auditory and non-auditory brain regions. Moreover, we consider how the identification of the neuronal mechanisms underlying the different forms of tinnitus would benefit from larger studies, replication and comprehensive clinical assessment of patients. PMID- 26373475 TI - Antibody-reactive class I epitopes defined by pairs of mismatched eplets and self eplets. AB - The identification of human leukocyte antigen (HLA) antibodies in the sera of candidates awaiting organ transplantation has evolved over time. This has been possible because of the introduction of more sensitive techniques and to the increasing focus on the structural aspects of the HLA epitopes. The use of the HLAMatchmaker algorithm in the analysis of positive sera and the verification of HLA ABC epitopes in the HLA Epitope Registry website provide new stimuli on the interpretation of antibody reactivity. The epitopes defined by eplet pairs often involve a nonself-eplet and a self-eplet (nonself-self paradigm), suggesting that the antibody response to an HLA mismatch must have an auto-reactive component. Here, we report an application of the nonself-self paradigm that provides a basis for better knowledge and interpretation of HLA-antibody reactivity in Luminex assays with single alleles. PMID- 26373476 TI - Variability of the caprine whey protein genes and their association with milk yield, composition and renneting properties in the Sarda breed: 2. The BLG gene. AB - The variability of the promoter region and the 3'UTR (exon-7) of the BLG gene, encoding the beta-lactoglobulin, was investigated by sequencing in 263 lactating Sarda goats in order to assess its association with milk traits. Milk traits included: milk yield, fat, total protein and lactose content, pH, daily fat and protein yield (DFPY), freezing point, milk energy, somatic cell count, total microbial mesophilic count, rennet coagulation time (RCT), curd firming rate (k20) and curd firmness (a30). A total of 7 polymorphic sites were detected and the sequence analysed was given accession number KM817769. Only three SNPs (c. 381C>T, c.-323C>T and c.*420C>A) had minor allele frequency higher than 0.05. The effects of farm, stage of lactation and the interaction farm * stage of lactation significantly influenced all the milk traits (P T and c.*420C>A (P T (P < 0.001). The c.-381TT homozygous goats showed lower pH, RCT and k20 than c.-381CT (P < 0.05). In conclusion the polymorphism of the goat BLG gene did not affect the total protein content of the Sarda goat milk, and only weakly influenced RCT and k20. On the other hand, an interesting effect on milk yields and DFPY emerged in two SNPs. This information might be useful in dairy goat breeding programs. PMID- 26373471 TI - Social cognition in schizophrenia. AB - Individuals with schizophrenia exhibit impaired social cognition, which manifests as difficulties in identifying emotions, feeing connected to others, inferring people's thoughts and reacting emotionally to others. These social cognitive impairments interfere with social connections and are strong determinants of the degree of impaired daily functioning in such individuals. Here, we review recent findings from the fields of social cognition and social neuroscience and identify the social processes that are impaired in schizophrenia. We also consider empathy as an example of a complex social cognitive function that integrates several social processes and is impaired in schizophrenia. This information may guide interventions to improve social cognition in patients with this disorder. PMID- 26373477 TI - Elemental Distribution in Multilayer Systems by Laser-Assisted Atom Probe Tomography with Various Analysis Directions. AB - Elemental distributions in a magnetic multilayer system with the structure Si substrate/Ta/NiFe/Ru/CoFeB/Ru/NiFe were studied using atom probe tomography (APT) along different analysis directions. The distributions of Ru and B atoms, which require a high evaporation field, were strongly influenced by the APT analysis direction. In particular, B in the CoFeB layer appeared near the interface with the lower Ru layer when the analysis was anti-parallel to the film growth direction, while B atoms were observed at the other side of the CoFeB layer when the analysis was parallel to the film growth direction. Moreover, when the analysis was perpendicular to the film growth direction, a homogenous distribution of B atoms was found within the CoFeB layer. Owing to this B behavior, the underlying Ru layer was affected in both of these analysis directions. In APT measurements of such a multilayer system composed of a stack of different evaporation field materials, evaluation of the elemental distribution around interfaces should be performed from more than one analysis direction. PMID- 26373478 TI - Flexible shift patterns work for everyone. PMID- 26373479 TI - Setting the wheels in motion for sepsis. PMID- 26373480 TI - Trusts urge the government to let more overseas nurses into the UK. PMID- 26373481 TI - Staff may prefer 12-hour shifts, but longer hours lead to burnout. PMID- 26373473 TI - Endocannabinoid signalling in reward and addiction. AB - Brain endocannabinoid (eCB) signalling influences the motivation for natural rewards (such as palatable food, sexual activity and social interaction) and modulates the rewarding effects of addictive drugs. Pathological forms of natural and drug-induced reward are associated with dysregulated eCB signalling that may derive from pre-existing genetic factors or from prolonged drug exposure. Impaired eCB signalling contributes to dysregulated synaptic plasticity, increased stress responsivity, negative emotional states and cravings that propel addiction. Understanding the contributions of eCB disruptions to behavioural and physiological traits provides insight into the eCB influence on addiction vulnerability. PMID- 26373482 TI - Holidaying nurse helps refugees. PMID- 26373484 TI - NHS funding for private care 'should be doubled'. PMID- 26373483 TI - Senior PHE figure urges school nurses to consider wearing a uniform again. PMID- 26373485 TI - Prison charities say support for families needed. PMID- 26373487 TI - Lack of sex advice puts group at risk. PMID- 26373488 TI - 'Be aware that even small incidents can be traumatic'. PMID- 26373489 TI - Warning over dehydration among nurses and doctors. PMID- 26373490 TI - Call for support and standardising of clinical nurse educator's role. PMID- 26373491 TI - Who counts the cost of patients spending their own care budget? PMID- 26373497 TI - Meningitis. PMID- 26373498 TI - A generation gap in career expectations. PMID- 26373499 TI - Preparing to fly into the Twittersphere. PMID- 26373500 TI - Thinking big on quality. PMID- 26373511 TI - ICE (In Case of Emergency). PMID- 26373509 TI - Nursing Careers. PMID- 26373513 TI - If union members unite and get their voices heard, we are more powerful. PMID- 26373514 TI - Nurses should be exempt from changes to immigration rules. PMID- 26373515 TI - First aid is a critical element of community-focused care planning. PMID- 26373517 TI - Innovative educational schemes will help solve nursing shortage. PMID- 26373518 TI - It is unfair to say nurses don't provide adequate diabetes care. PMID- 26373521 TI - How to wash your hands effectively. PMID- 26373522 TI - Effect of technology on undertaking nursing observations. AB - It is recognised that there is a shared responsibility for ensuring nursing students are competent to carry out and interpret manual nursing observations in accordance with Nursing and Midwifery Council guidelines. Many nurses rely on electronic medical devices to determine baseline observations in all clinical settings. This could be perceived as detrimental to patient care, since nurses are no longer using their senses fully to assess patients. This, in turn, compromises the competence and confidence of nursing students to carry out the essential skills of monitoring and recording vital signs to ensure they are fit for practice. PMID- 26373523 TI - Transforming dementia care in acute hospitals. AB - This article provides an overview of current developments to support improvements in dementia care in acute general hospital settings. It considers the urgent need for improvement along with the effectiveness of current approaches in achieving change and delivering person-centred care. The process and outcomes of a development programme carried out by the Royal College of Nursing and evaluated by the University of Worcester are described. This programme supported clinical nurse leaders in developing dementia care in nine acute general hospitals by use of an action learning approach. Recommendations are made for a more systematic approach to developing practice that considers the context and culture of acute hospital care for people with dementia. The need for investment in clinical leaders and dementia specialists who can assist improvements and support change is emphasised. PMID- 26373524 TI - Recognition and management of asthma in children and young people. AB - Asthma is a common childhood disorder that has global significance. Developing an understanding of the aetiology, effects, diagnosis and management of the disorder enables healthcare practitioners to reduce the physical, psychological and social effects of asthma on children, families and healthcare systems. This article refers to the Scottish Intercollegiate Guidelines Network and British Thoracic Society guideline on the management of asthma, and enables the reader to incorporate this guidance into their practice. PMID- 26373525 TI - Economic evaluation. PMID- 26373526 TI - Champions needed. PMID- 26373528 TI - Striking the right staff balance. PMID- 26373529 TI - It's so rewarding. PMID- 26373530 TI - An experience I cherish. PMID- 26373531 TI - Comparative outcome analysis of home-initiated non-medical interventions among toddlers with orally ingested substances. AB - BACKGROUND: Poison management guidelines recommend contacting or visiting poison centers directly after exposure. However, some parents initiated non-medical interventions on their children before visiting these centers. Aim was to evaluate the clinical and hospital outcomes of such practices among toddlers with orally ingested medication or chemical substances at a tertiary care facility. METHODS: Retrospective cohort, based on four-arm outcome analysis. Exposures were gender, age, body mass index, arrival time to facility (hours) presented in Median [Interquartile range]. Clinical outcomes were vital signs, physical examination, diagnostic tests; Hospital outcomes were in-hospital admission, length of hospital stay (hours) presented in Median [Interquartile range], hospital cost ($US). Bivariate analysis (nonparametric tests), binary logistic/linear regression were conducted. Significance at p < 0.05. RESULTS: Between 2009-2011, 165 (all previously healthy) toddlers were (Males = 58 %, females = 42 %) and had normal weights in 70 %. Witnessed incidents were in 85 %. Two control groups [Medication (control) = 72, Chemical (control) = 48] directly visited the facility after incident, while two intervention groups [Medication (intervention) = 27, Chemical (intervention) = 18] received orally administered water, salt/sugar solutes, milk/yogurt, lemon juice and/or manually induced vomiting before the visit. Abnormal clinical outcomes in total were in vital signs = 15 %, physical examination = 42 % and diagnostic tests = 26 %; hospital outcomes were admission = 16 %, length of stay range (2 hours-7.5 days), cost range (667-11,500). Bivariate analysis: Length of stay in Medication (intervention) = 9[5.4-12.0] hours significantly higher than Medication (control) = 5[2.7-7.5] hours, p = 0.003; abnormal physical examination in Chemical (intervention) = 77.8 % significantly higher than Chemical (control) = 37.5 %, p = 0.004. In regression: intervention significantly increased length of stay (t = 0.213, adj. P = 0.035); lower weight toddlers were at higher risk of admission (Beta = -0.51, adj. P = 0.018); delayed arrival time significantly increased abnormal physical examination (Beta = 0.29, adj. P = 0.003). No significant control/intervention group differences regarding abnormal vital signs (adj. P = 0.148), physical examination (adj. P = 0.781), diagnostic tests (adj. P = 0.285), admission (adj. P = 0.499), and cost (adj. P = 0.102). CONCLUSION: Home-initiated non-medical interventions didn't improve the clinical and hospital outcomes. It has delayed the arrival time to emergency department, which added the risk of encountering abnormal physical examination, and in return increased the average length of hospital stay. PMID- 26373532 TI - Pylorus-preserving total pancreatectomy for metastatic renal cell carcinoma: a case report. AB - INTRODUCTION: Resectable isolated multiple metastases to the pancreas from renal cell carcinoma are rare. In this report, we describe a patient with multiple metastases of renal cell carcinoma to the pancreas who was treated with pylorus preserving total pancreatectomy. CASE PRESENTATION: The patient was a 58-year-old Asian woman who had undergone right nephrectomy for renal cell carcinoma 20 years earlier. In 2008, she was diagnosed with multiple metastases of renal cell carcinoma to the pancreas by abdominal computed tomography during routine follow up for renal cell carcinoma. (18)F-2-fluoro-2-deoxyglucose positron emission tomography/computed tomography showed no accumulation in her body other than the pancreas. Because of concerns about her quality of life after total pancreatectomy, she underwent pylorus-preserving total pancreatectomy. After the resection, her control of blood sugar and quality of life were generally satisfactory. She died as a result of gastrointestinal bleeding 35 months after undergoing pancreatectomy. CONCLUSIONS: Pancreatic metastasectomy should be considered, even for multiple metastases, when the primary tumor is renal cell carcinoma and the metastatic lesions are isolated. PMID- 26373533 TI - Major arterial events in patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors: a meta-analysis. AB - There is growing evidence that tyrosine kinase inhibitors (TKIs) may be associated with an increased risk of arterial events. We performed a meta analysis to estimate the incidence of arterial events in patients with CML treated with TKIs. We identified 29 studies enrolling 15,706 patients. The incidence rates of composite of major arterial events were 0.8 per 100 patient years for non-TKI treatments, 1.1 per 100 patient-years for dasatinib, 0.1 per 100 patient-years for imatinib, 0.4 per 100 patient-years for bosutinib, 2.8 per 100 patient-years for nilotinib and 10.6 per 100 patient-years for ponatinib. The relative risk (RR) for nilotinib compared with imatinib suggests a significantly increased risk of the composite of major arterial events with nilotinib treatment (RR 5.3; 95%CI 3.0-9.3, p < 0.001). This study demonstrates that, patients who received nilotinib or ponatinib had a greater number of major arterial events when compared to non-TKI-, imatinib-, dasatinib- and bosutinib-treated patients. PMID- 26373534 TI - Chemical Bonding of Transition-Metal Co13 Clusters with Graphene. AB - We carried out density functional calculations to study the adsorption of Co13 clusters on graphene. Several free isomers were deposited at different positions with respect to the hexagonal lattice nodes, allowing us to study even the hcp 2d isomer, which was recently obtained as the most stable one. Surprisingly, the Co13 clusters attached to graphene prefer icosahedron-like structures in which the low-lying isomer is much distorted; in such structures, they are linked with more bonds than those reported in previous works. For any isomer, the most stable position binds to graphene by the Co atoms that can lose electrons. We find that the charge transfer between graphene and the clusters is small enough to conclude that the Co-graphene binding is not ionic-like but chemical. Besides, the same order of stability among the different isomers on doped graphene is kept. These findings could also be of interest for magnetic clusters on graphenic nanostructures such as ribbons and nanotubes. PMID- 26373535 TI - Coronin 2A (CRN5) expression is associated with colorectal adenoma-adenocarcinoma sequence and oncogenic signalling. AB - BACKGROUND: Coronin proteins are known as regulators of actin-based cellular processes, and some of them are associated with the malignant progression of human cancer. Here, we show that expression of coronin 2A is up-regulated in human colon carcinoma. METHODS: This study included 26 human colon tumour specimens and 9 normal controls. Expression and localisation of coronin 2A was studied by immunohistochemistry, immunofluorescence imaging, cell fractionation, and immunoblotting. Functional roles of coronin 2A were analysed by over expression and knock-down of the protein. Protein interactions were studied by co immunoprecipitation and pull-down experiments, mass spectrometry analyses, and in vitro kinase and methylation assays. RESULTS: Histopathological investigation revealed that the expression of coronin 2A in colon tumour cells is up-regulated during the adenoma-adenocarcinoma progression. At the subcellular level, coronin 2A localised to multiple compartments, i.e. F-actin stress fibres, the front of lamellipodia, focal adhesions, and the nuclei. Over-expression of coronin 2A led to a reduction of F-actin stress fibres and elevated cell migration velocity. We identified two novel direct coronin 2A interaction partners. The interaction of coronin 2A with MAPK14 (mitogen activated protein kinase 14 or MAP kinase p38alpha) led to phosphorylation of coronin 2A and also to activation of the MAPK14 pathway. Moreover, coronin 2A interacted with PRMT5 (protein arginine N methyltransferase 5), which modulates the sensitivity of tumour cells to TRAIL induced cell death. CONCLUSIONS: We show that increased expression of coronin 2A is associated with the malignant phenotype of human colon carcinoma. Moreover, we linked coronin 2A to MAPK14 and PRMT5 signalling pathways involved in tumour progression. PMID- 26373537 TI - Azithromycin-containing intermittent preventive treatment in pregnancy affects gestational weight gain, an important predictor of birthweight in Papua New Guinea - an exploratory analysis. AB - In Papua New Guinea, intermittent preventive treatment with sulphadoxine pyrimethamine and azithromycin (SPAZ-IPTp) increased birthweight despite limited impact on malaria and sexually transmitted infections. To explore possible nutrition-related mechanisms, we evaluated associations between gestational weight gain (GWG), enrolment body mass index (BMI) and mid-upper arm circumference (MUAC), and birthweight. We investigated whether the increase in birthweight associated with SPAZ-IPTp may partly be driven by a treatment effect on GWG. The mean GWG rate was 393 g/week (SD 250; n = 948). A 100 g/week increase in GWG was associated with a 14 g (95% CI 2.6, 25.4) increase in birthweight (P = 0.016). Enrolment BMI and MUAC also positively correlated with birthweight. SPAZ IPTp was associated with increased GWG [58 g/week (26, 900), P < 0.001, n = 948] and with increased birthweight [48 g, 95% CI (8, 880), P = 0.019] when all eligible women were considered (n = 1947). Inclusion of GWG reduced the birthweight coefficient associated with SPAZ-IPTp by 18% from 44 to 36 g (n = 948), although SPAZ-IPTp was not significantly associated with birthweight among women for whom GWG data were available (P = 0.13, n = 948). One month post partum, fewer women who had received SPAZ-IPTp had a low post-partum BMI (<18.5 kg m(-2) ) [adjusted risk ratio: 0.55 (95% CI 0.36, 0.82), P = 0.004] and their babies had a reduced risk of wasting [risk ratio 0.39 (95% CI 0.21, 0.72), P = 0.003]. SPAZ-IPTp increased GWG, which could explain its impact on birthweight and maternal post-partum BMI. Future trials of SPAZ-IPTp must incorporate detailed anthropometric evaluations to investigate mechanisms of effects on maternal and child health. PMID- 26373536 TI - Population expansion and gene flow in Giardia duodenalis as revealed by triosephosphate isomerase gene. AB - BACKGROUND: Giardia duodenalis is a protozoan parasite that can cause significant diarrhoeal diseases. Knowledge of population genetics is a prerequisite for ascertaining the invasion patterns of this parasite. In order to infer evolutionary patterns that could not be uncovered based on the morphological features, a population genetic study with the incorporation of molecular marker was carried out to access the genetic structure of G. duodenalis isolated from the Malaysian population and the global populations. METHODS: A total of 154 samples positive for Giardia, collected from different Malaysian communities, were subjected to DNA amplification and sequencing targeting three genetic loci (tpi, gdh, and bg). The tpi sequences together with sequences from the global data obtained from the NCBI GenBank were used for genetic diversity analyses including identification of haplotypes, haplotype diversity, nucleotide diversity, Tajima's D and Fu and Li's D, gene flow and genetic differentiation tests. RESULTS: Analysis of the Malaysian and global data showed that assemblages A, B, and E (the most prevalent assemblages in humans and animals), have different levels of genetic diversity. Assemblage B had the highest level of both haplotype diversity and nucleotide diversity, followed by assemblage E. The analysis also revealed population expansion and high gene flow in all assemblages. No clear genetic structure was observed across five continents (i.e., the Americas, Europe, Asia, Australia and Africa). However, median joining network of assemblage B formed a cluster that was exclusively isolated from Asia while other haplotypes were well dispersed across the continents. CONCLUSIONS: This study provides new insight into the genetic diversity of Giardia assemblages in different geographical regions. The significant result shown by gene flow and genetic differentiation analyses as well as test of neutrality among the populations should have brought a clearer picture to the dynamics and distribution of Giardia infection. PMID- 26373538 TI - A comparison of a multistate inpatient EHR database to the HCUP Nationwide Inpatient Sample. AB - BACKGROUND: The growing availability of electronic health records (EHRs) in the US could provide researchers with a more detailed and clinically relevant alternative to using claims-based data. METHODS: In this study we compared a very large EHR database (Health Facts(c)) to a well-established population estimate (Nationwide Inpatient Sample). Weighted comparisons were made using t-value and relative difference over diagnoses and procedures for the year 2010. RESULTS: The two databases have a similar distribution pattern across all data elements, with 24 of 50 data elements being statistically similar between the two data sources. In general, differences that were found are consistent across diagnosis and procedures categories and were specific to the psychiatric-behavioral and obstetrics-gynecology services areas. CONCLUSIONS: Large EHR databases have the potential to be a useful addition to health services researchers, although they require different analytic techniques compared to administrative databases; more research is needed to understand the differences. PMID- 26373541 TI - Are We a Step Further Toward a Useful Biomarker? PMID- 26373539 TI - Altered G Protein Coupling in Olfactory Neuroepithelial Cells From Patients With Schizophrenia. AB - Increasing evidence suggests that olfactory dysfunction is an endophenotype of schizophrenia, and thus the olfactory system can be studied both in relation to this sensory dysfunction and also as a means of examining pathophysiologic mechanisms of schizophrenia. In this study, we examined human olfactory neuroepithelial (ON) biopsy tissues and their in vitro culture cells for ligand induced guanine nucleotide-binding protein (G protein) activation and downstream signaling. We assessed the binding of a nonhydrolyzable GTP analogue [(35)S]GTPgammaS binding to specific G protein subtypes in response to odorants, dopamine, or serotonin in ON cell membranes from matched schizophrenia-control subjects. In response to odorant mixtures, we found decreased [(35)S]GTPgammaS binding to Galphas/olf in schizophrenia patients. These changes were not mediated by mRNA expression of key molecules of G protein coupling, including adenylate cyclase III (ACIII), protein kinase A (PKA), protein kinase Cgamma (PKCgamma), or Galphas or Galphaolf in ON cells or ON biopsy tissues. In contrast, dopamine (DA) and serotonin (5HT)-induced S(35)-GTPgammaS binding to Galphas/olf and Galphaq/11 were significantly increased in schizophrenia cases, while these parameters were strikingly reduced by in vitro treatment with antipsychotics. Patients with schizophrenia exhibit increases in electrolfactogram (EOG) recordings, suggesting enhanced odorant-induced activation. Our results of decreased odorant-induced G protein activation may point further downstream for underlying mechanisms for increased EOG measures. Increased G protein activation in response to DA and 5HT may suggest increased postreceptor DA or 5HT signaling as an additional mechanism of dopaminergic or serotonergic dysregulation in schizophrenia. PMID- 26373542 TI - Response surface optimization of the thermal acid pretreatment of sugar beet pulp for bioethanol production using Trichoderma viride and Saccharomyces cerevisiae. AB - BACKGROUND: Worldwide nowadays, relying on the second generation bioethanol from the lignocellulosic feedstock is a mandatory aim. However, one of the major drawbacks for high ethanol yield is the physical and chemical pretreatment of this kind of feedstock. As the pretreatment is a crucial process operation that modifies the lignocellulosic structure and enhances its accessibility for the high cost hydrolytic enzymes in an attempt to maximize the yield of the fermentable sugars. The objective of this work was to optimize and integrate a physicochemical pretreatment of one of the major agricultural wastes in Egypt; the sugar beet pulp (SBP) and the enzymatic saccharification of the pretreated SBP using a whole fungal cells with a separate bioethanol fermentation batch processes to maximize the bioethanol yield. METHODS AND RESULTS: The response surface methodology was employed in this study to statistically evaluate and optimize the conditions for a thermal acid pretreatment of SBP. The significance and the interaction effects of the concentrations of HCl and SBP and the reaction temperature and time were studied using a three-level central composite design of experiments. A quadratic model equation was obtained to maximize the production of the total reducing sugars. The validity of the predicted model was confirmed. The thermally acid pretreated SBP was further subjected to a solid state fermentation batch process using Trichoderma viride F94. The thermal acid pretreatment and fungal hydrolyzes were integrated with two parallel batch fermentation processes of the produced hydrolyzates using Saccharomyces cerevisiae Y39, that yielded a total of ~ 48 g/L bioethanol, at a conversion rate of ~ 0.32 g bioethanol/ g SBP. CONCLUSION: Applying the proposed integrated process, approximately 97.5 gallon of ethanol would be produced from a ton (dry weight) of SBP. PMID- 26373540 TI - Impact of Different Childhood Adversities on 1-Year Outcomes of Psychotic Disorder in the Genetics and Psychosis Study. AB - While the role of childhood adversity in increasing the risk of psychosis has been extensively investigated, it is not clear what the impact of early adverse experiences is on the outcomes of psychotic disorders. Therefore, we investigated associations between childhood adversity and 1-year outcomes in 285 first presentation psychosis patients. Exposure to childhood adversity prior to 17 years of age was assessed using the Childhood Experience of Care and Abuse Questionnaire. Data on illness course, symptom remission, length of psychiatric hospitalization, compliance with medication, employment, and relationship status were extracted from clinical records for the year following first contact with mental health services for psychosis. Seventy-one percent of patients reported exposure to at least 1 type of childhood adversity (physical abuse, sexual abuse, parental separation, parental death, disrupted family arrangements, or being taken into care). No robust associations were found between childhood adversity and illness course or remission. However, childhood physical abuse was associated with almost 3-fold increased odds of not being in a relationship at 1-year follow up compared to patients who did not report such adverse experiences. There was also evidence of a significant association between parental separation in childhood and longer admissions to psychiatric wards during 1-year follow-up and 2-fold increased odds of noncompliance with medication compared to those not separated from their parents. Therefore, our findings suggest that there may be some specificity in the impact of childhood adversity on service use and social functioning among psychosis patients over the first year following presentation to mental health services. PMID- 26373543 TI - Erratum to: Phylogeography of the sand dune ant Mycetophylax simplex along the Brazilian Atlantic Forest coast: remarkably low mtDNA diversity and shallow population structure. PMID- 26373544 TI - "Dancing inside the ball": the structures and nonlinear optical properties of three Sc2S@C3v(8)-C82 isomers. AB - Recently, the crystal structures and electrochemical properties of the isomers (Sc2S "trapped" in C82) have been reported, in which the Sc2S is located inside the different positions of the C82 cage. In the present work, three isomers of endohedral metallofullerenes Sc2S@C3v(8)-C82 (A, B, and C) have been designed to explore the effect of the position of Sc2S on their interaction energies and nonlinear optical properties. Among three isomers, the Sc2S is located in different positions of the C82 cage: the angles of Sc-S-Sc in A, B, and C are 104.9, 114.8, and 115.7 degrees , respectively. Furthermore, the analysis of natural bond orbital (NBO) charge indicates that the electron-transfer is from the Sc2S to the adjacent carbon atoms of the C82 cage. The interaction energy of B is the smallest among three isomers which is -226.2 kcal mol(-1). It was worth mentioning that their first hyperpolarizabilities (beta tot) were studied, we found that their beta tot values were related to the positions of Sc2S: C (2100) > B (1191) > A (947 au). We hope that the present work can provide a new strategy to promote the nonlinear optical properties of endohedral metallofullerenes by changing the positions of the encapsulated molecular. Graphical abstract Three isomers of endohedral metallofullerenes Sc2S@C3v(8)-C82 (A, B, and C) have been designed to explore the position effect of Sc2S on the interaction energies and nonlinear optical properties. Among three isomers, the Sc2S in B has the most stable position. Significantly, the first hyperpolarizability is related to the position of Sc2S inside the C82 cage, which provides a novel strategy to enhance the first hyperpolarizability by the Sc2S revolving inside the C82 cage. PMID- 26373545 TI - Robot-assisted Partial Nephrectomy for Endophytic Tumors. AB - Robot-assisted partial nephrectomy (RAPN) has gained increasing popularity in the management of renal masses due to its technical feasibility and shorter learning curve with superior perioperative outcomes compared to laparoscopic partial nephrectomy (LPN). Given the cumulation of surgical experience on RAPN, the indication for RAPN has been extended to more challenging, complex cases, such as hilar or endophytic tumors. Renal masses that are completely endophytic can be very challenging to surgeons. These cases are associated with poor recognition of mass extension, higher risk of inadvertent vascular, or pelvicalyceal system injury. As a result, this can lead to potential positive surgical margin, difficulty in performing renorrhaphy as well as higher perioperative complication rates. There is few evidence of oncologic and functional outcomes of RAPN on treating endophytic masses. Therefore, the objective of this review is to critically analyze the current evidence and to provide a summary on the outcomes of RAPN for endophytic renal masses. PMID- 26373546 TI - Red nucleus glutamate facilitates neuropathic allodynia induced by spared nerve injury through non-NMDA and metabotropic glutamate receptors. AB - Previous studies have demonstrated that glutamate plays an important role in the development of pathological pain. This study investigates the expression changes of glutamate and the roles of different types of glutamate receptors in the red nucleus (RN) in the development of neuropathic allodynia induced by spared nerve injury (SNI). Immunohistochemistry indicated that glutamate was constitutively expressed in the RN of normal rats. After SNI, the expression levels of glutamate were significantly increased in the RN at 1 week and reached the highest level at 2 weeks postinjury compared with sham-operated and normal rats. The RN glutamate was colocalized with neurons, oligodendrocytes, and astrocytes but not microglia under physiological and neuropathic pain conditions. To elucidate further the roles of the RN glutamate and different types of glutamate receptors in the development of neuropathic allodynia, antagonists to N-methyl-D-aspartate (NMDA), non-NMDA, or metabotropic glutamate receptors (mGluRs) were microinjected into the RN contralateral to the nerve-injury side of rats with SNI, and the paw withdrawal threshold (PWT) was dynamically assessed with von Frey filaments. Microinjection of the NMDA receptor antagonist MK-801 into the RN did not show any effect on SNI-induced mechanical allodynia. However, microinjection of the non-NMDA receptor antagonist 6,7-dinitroquinoxaline-2,3(1H,4H)-dione or the mGluR antagonist (+/-)-alpha-methyl-(4-carboxyphenyl) glycine into the RN significantly increased the PWT and alleviated SNI-induced mechanical allodynia. These findings suggest that RN glutamate is involved in regulating neuropathic pain and facilitates the development of SNI-induced neuropathic allodynia. The algesic effect of glutamate is transmitted by the non-NMDA glutamate receptor and mGluRs. PMID- 26373547 TI - Eosinophilia and parotitis occurring early in clozapine treatment. AB - CASE PRESENTATION: Mr. S is a 32-year-old male with schizophrenia. Due to poor responses to various antipsychotic medications, he was started on clozapine with the dose titrated to 300 mg/day during a 4-week period. The weekly checks of the complete blood cell count showed gradual increases in the eosinophil count from normal values to 4320 per mm(3). Mr. S did not have any symptoms except some increased salivation. Clozapine was suspended, and eosinophils gradually began to decline to the normal range. Clozapine was subsequently re-started and there were no changes in eosinophil counts. Mr. S exhibited improvement of symptoms but complained of acute auricular pain and increased salivation, 8 weeks after clozapine rechallenge. He also developed a swelling of his both parotid glands. The diagnosis of clozapine-induced parotitis was suggested. Symptomatic medication was prescribed with a favorable outcome. CONCLUSION: We report a case of a patient who developed eosinophilia shortly after clozapine use, and then developed parotitis. There is debate in the literature over how to manage these complications of clozapine treatment. Generally they do not warrant clozapine discontinuation. PMID- 26373548 TI - Genetic influence on visual outcomes of polypoidal choroidal vasculopathy. PMID- 26373549 TI - Assessment of potential vessel segmentation pitfalls in the analysis of blood flow velocity using the Retinal Function Imager. AB - PURPOSE: The purpose of our study was to investigate the potential pitfalls associated with different vessel segmentation methods using the built-in software of the Retinal Function Imager (RFI) for the analysis of retinal blood flow velocity (BFV). METHODS: Ten eyes of nine healthy subjects were enrolled in the study. Retinal blood flow measurements were obtained with the RFI device with a 20 degrees field of view imaging. The same grader segmented the retinal vasculature using the RFI software in both sessions, with segments ranging in length from 50 to 100 pixels ("short segments") and 100-200 pixels ("long segments"). The blood flow velocities for the arteriolar and venular system were calculated, and the percentage of excluded vessel segments with high coefficients of variation (>45 %) was recorded and compared by paired t test. Spearman's correlation was used to analyze the relationship between measurements by the two vessel segmentation methods. RESULTS: The number of analyzed vessel segments did not differ significantly between the two groups (28.6 +/- 2.6 short and 26.7 +/- 4.6 long segments), while the percentage of acceptable segments was significantly higher in the long segment group (65.2 +/- 11.4 % vs 85.2 +/- 5.87 %, p = 0.001). In the short segment group, more than 15 % of vessel segments were rejected in all subjects, while in the long segment group only three subjects had a rejection rate of greater than 15 % (16.7 %, 18.7 % and 28 %). Both arteriolar and venular velocities were lower in the short segment group, although it reached significance only for arteriolar velocities (3.93 +/- 0.55 vs. 4.45 +/- 0.76 mm/s, p = 0.036 and 2.95 +/- 0.56 vs. 3.17 +/- 0.84 mm/s, p = 0.201 for arterioles and venules, respectively). Only venular velocities showed significant correlation (p = 0.003, R (2) = 0.67) between the two groups. CONCLUSIONS: Our results suggest that BFV measurements by the RFI may be affected by segment length, and care should therefore be taken in choosing vessel segment lengths used during the analysis of RFI data. Long segments of 100-200 pixels (400-800 MUm) seem to provide more robust measurements, which can be explained by the analysis methodology of the RFI device. PMID- 26373550 TI - BMPR2 spruces up the endothelium in pulmonary hypertension. PMID- 26373551 TI - Replication-competent adenoviruses with the type 35-derived fiber-knob region achieve reactive oxygen species-dependent cytotoxicity and produce greater toxicity than those with the type 5-derived region in pancreatic carcinoma. AB - Pancreatic carcinoma is relatively resistant to chemotherapy and cell death induced by replication of adenoviruses (Ad) can be one of the therapeutic options. Transduction efficacy of conventional type 5 Ad (Ad5) is however low and the cytotoxic mechanism by replication-competent Ad was not well understood. We constructed replication-competent Ad5 of which the E1A promoter region was replaced with a transcriptional regulatory region of the midkine, the survivin or the cyclooxygenase-2 gene, all of which were expressed at a high level in human tumors. We also prepared replication-competent Ad5 that were activated with the same region but had the type 35 Ad-derived fiber-knob region (AdF35) to convert the major cellular receptor for Ad infection from the coxsackie adenovirus receptor to CD46 molecules. Replication-competent AdF35 that were activated with the exogenous region produced cytotoxic effects on human pancreatic carcinoma cells greater than the corresponding Ad5 bearing with the same regulatory region. Cells infected with the AdF35 showed cytopathic effects and increased sub-G1 fractions. Caspase-9, less significantly caspase-8 and poly (ADP-ribose) polymerase, but not caspase-3 was cleaved and expression of molecules involved in autophagy and caspase-independent cell death pathways remained unchanged. Nevertheless, H2A histone family member X molecules were phosphorylated, and N acetyl-L-cystein, an inhibitor for reactive oxygen species, suppressed the AdF35 mediated cytotoxicity. These data indicated a novel mechanism of Ad-mediated cell death and suggest a possible clinical application of the fiber-knob modified Ad. PMID- 26373552 TI - [Physiotherapy and physical therapy in pain management]. AB - Patients attend physiotherapy and physical therapy (PT) due to pain problems and/or functional impairments. Although the main focus for therapists has traditionally been physical examination and treatment of tissue structures and biomechanics, over the last few decades a growing body of research has highlighted the importance of central nervous system processing and psychosocial contributors to pain perception. Treatment with PT aims to reduce disability and suffering by reducing pain and increasing tolerance to movement. In Germany, pain management conducted by physiotherapists is currently undergoing major changes. Firstly, PT education is transitioning from a vocational to a degree level and additionally new concepts for improved multidisciplinary treatment approaches are being developed. However, there still remain substantial differences between therapists working in multidisciplinary pain clinics and those following medical referral in private practices. This article provides information on how national and international impulses have contributed to the development of different concepts of passive therapies and active/functional pain rehabilitation in Germany. In the future PT will need to provide more evidence about efficiency and modes of actions for different treatment options to selectively reason the application to patients with acute, subacute and chronic pain. PMID- 26373553 TI - PIWIL2 promotes progression of non-small cell lung cancer by inducing CDK2 and Cyclin A expression. AB - BACKGROUND: PIWI proteins have important roles in tumorigenesis due to their interaction with piRNAs. Recent studies suggest that PIWI proteins affect prognosis of various cancers. METHODS: In the present study, PIWI genes expression was assayed in non-small cell lung cancer (NSCLC). To determine the effects of PIWIL2 on NSCLC cells, overexpression and interference assays were performed using the A549 and H460 cell lines. The tumor formation model was performed to demonstrate the effects of PIWIL2 on tumor formation in vivo. RESULTS: PIWIL2 was increased both at the RNA and protein level in malignant cancer tissues compared with adjacent normal tissue. Moreover, increased PIWIL2 gene expression was negatively correlated with prognosis in NSCLC patients. Overexpression and interference of PIWIL2 promoted and depressed cell proliferation, respectively. Meanwhile, PIWIL2 interference arrested cells at the G2/M stage. In addition, we found that CDK2 and Cyclin A expression were correlated with PIWIL2 expression. Moreover, transfection of PIWIL2 promoted tumor growth in nude mice. CONCLUSION: Our findings shed light on the function of PIWIL2 in NSCLC and suggest potential prognostic and therapeutic value. PMID- 26373554 TI - Contextual, organizational and ecological effects on the variations in hospital readmissions of rural Medicare beneficiaries in eight southeastern states. AB - The enactment of the Patient Protection and Affordable Care Act (ACA) has been expected to improve the coverage of health insurance, particularly as related to the coordination of seamless care and the continuity of elder care among Medicare beneficiaries. The analysis of longitudinal data (2007 through 2013) in rural areas offers a unique opportunity to examine trends and patterns of rural disparities in hospital readmissions within 30 days of discharge among Medicare beneficiaries served by rural health clinics (RHCs) in the eight southeastern states of the Department of Health & Human Services (DHHS) Region 4. The purpose of this study is twofold: first, to examine rural trends and patterns of hospital readmission rates by state and year (before and after the ACA enactment); and second, to investigate how contextual (county characteristic), organizational (clinic characteristic) and ecological (aggregate patient characteristic) factors may influence the variations in repeat hospitalizations. The unit of analysis is the RHC. We used administrative data compiled from multiple sources for the Centers of Medicare and Medicaid Services for a period of seven years. From 2007 to 2008, risk-adjusted readmission rates increased slightly among Medicare beneficiaries served by RHCs. However, the rate declined in 2009 through 2013. A generalized estimating equation of sixteen predictors was analyzed for the variability in risk-adjusted readmission rates. Nine predictors were statistically associated with the variability in risk-adjusted readmission rates of the RHCs pooled from 2007 through 2013 together. The declined rates were associated with by the ACA effect, Georgia, North Carolina, South Carolina, and the percentage of elderly population in a county where RHC is located. However, the increase of risk-adjusted rates was associated with the percentage of African Americans in a county, the percentage of dually eligible patients, the average age of patients, and the average clinical visits by African American patients. The sixteen predictors accounted for 21.52 % of the total variability in readmissions. This study contributes to the literature in health disparities research from the contextual, organizational and ecological perspectives in the analysis of longitudinal data. The synergism of multiple contextual, organizational and ecological factors, as shown in this study, should be considered in the design and implementation of intervention studies to address the problem of hospital readmissions through prevention and enhancement of disease management of rural Medicare beneficiaries. PMID- 26373555 TI - A new preparedness policy for EMS logistics. AB - Response time in emergency medical services (EMS) is defined as the interval for an ambulance to arrive the scene after receipt of a 911 call. When several ambulances are available upon the receipt of a new call, a decision of selecting an ambulance has to be made in an effort to reduce response time. Dispatching the closest unit available is commonly used in practice; however, recently the Preparedness policy was designed that is in a simplistic form yet being capable of securing a long-term efficiency. This research aims to improve the Preparedness policy, resolving several critical issues inherent in the current form of the policy. The new Preparedness policy incorporates a new metric of preparedness based on the notion of centrality and involves a tuning parameter, weight on preparedness, which has to be appropriately chosen according to operational scenario. Computational experiment shows that the new policy significantly improves the former policy robustly in various scenarios. PMID- 26373556 TI - Evaluation of bone scan index change over time on automated calculation in bone scintigraphy. AB - OBJECTIVE: Bone scintigraphy (bone scan) is useful in detecting metastatic bone lesions through visual assessment of hot spots. A semi-quantitative analysis method that evaluates bone scan images has been eagerly anticipated. BONENAVI is software that enables automatic assessment of bone scan index (BSI). BSI is useful for stratifying cancer patients and monitoring their therapeutic response. The purpose of this study was to evaluate the BONENAVI reading in determining BSI and hot spots at different time intervals after radioisotope injection. METHODS: We evaluated 32 patients, including 22 males and 10 females. Ten patients had breast cancer, 20 patients had prostate cancer, and 2 had malignant pheochromocytoma. Patients were injected with 740 MBq of (99m)Tc-methylene diphosphonate and bone scintigraphy was performed at 2, 4, and 6 h after injection on each patient. The BSI and the number of hot spots were obtained from BONENAVI software. Bone scan images were also visually assessed to exclude false positives due to artifacts. Analyses were performed in all lesions, selected true lesions, segment based and cancer type based. Non-parametric statistical analyses for pairwise multiple group comparison were performed using Friedman test followed with post hoc analysis. RESULTS: The BSIs and the number of hot spots were significantly increased with time, with significant differences between each of time points (P < 0.001). Analysis of regional BSI (rBSI) and hot spot number changes of selected 15 true lesions also showed similar increase (P < 0.001). In general, the pelvic segment was the most prone to rBSI changes and the chest segment was the most prone to hot spot number changes. Visual assessment showed that BONENAVI diagnosed some typical artifacts as metastases (hot spots). CONCLUSION: BONENAVI reading of BSIs and hot spot numbers was highly affected by acquisition time. In serial or follow-up examinations (in particular, for monitoring therapeutic efficacy), acquisition time should be fixed for each patient. Cautious interpretation should be made on segments with high physiological uptake. BONENAVI reading was prone to misinterpretation of artifacts. Visual assessment is necessary to rule out this possibility. PMID- 26373557 TI - A Model of Chloroplast Growth Regulation in Mesophyll Cells. AB - Chloroplasts regulate their growth to optimize photosynthesis. Quantitative data show that the ratio of total chloroplast area to mesophyll cell area is constant across different cells within a single species and also across species. Wild-type chloroplasts exhibit little scatter around this trend; highly irregularly shaped mutant chloroplasts exhibit more scatter. Here we propose a model motivated by a bacterial quorum-sensing model consisting of a switch-like signaling network that turns off chloroplast growth. We calculated the dependence of the location of the relevant saddle-node bifurcation on the geometry of the chloroplasts. Our model exhibits a linear trend, with linearly growing scatter dependent on chloroplast shape, consistent with the data. When modeled chloroplasts are of a shape that grows with a constant area-to-volume ratio (disks, cylinders), we find a linear trend with minimal scatter. Chloroplasts with area and volume that do not grow proportionally (spheres) exhibit a linear trend with additional scatter. PMID- 26373558 TI - Troglomorphism in the middle Triassic crinoids from Poland. AB - In this paper, we document the Middle Triassic marine fauna recovered from the fissure/cave system of Stare Gliny (southern Poland) developed in the Devonian host dolomite. The fossils are mostly represented by in situ preserved and small sized holdfasts of crinoids (Crinoidea) that are attached to the cave walls. Other fossils found in the cave infills include articulated brittle stars and brachiopods. Our findings constitute the oldest Mesozoic evidence for troglophile crinoids. We suggest that troglomorphism in these echinoderms was likely related to protection against predation, which underscores the magnitude of anti predatory adaptations to increased predation pressure that occurred during the Early Mesozoic Marine Revolution. PMID- 26373559 TI - Life history traits to predict biogeographic species distributions in bivalves. AB - Organismal fecundity (F) and its relationship with body size (BS) are key factors in predicting species distribution under current and future scenarios of global change. A functional trait-based dynamic energy budget (FT-DEB) is proposed as a mechanistic approach to predict the variation of F and BS as function of environmental correlates using two marine bivalves as model species (Mytilus galloprovincialis and Brachidontes pharaonis). Validation proof of model skill (i.e., degree of correspondence between model predictions and field observations) and stationarity (i.e., ability of a model generated from data collected at one place/time to predict processes at another place/time) was provided to test model performance in predicting the bivalve distribution throughout the 22 sites in the Central Mediterranean Sea under local conditions of food density and body temperature. Model skill and stationarity were tested through the estimate of commission (i.e., proportion of species' absences predicted present) and omission (i.e., proportion of presences predicted absent) errors of predictions by comparing mechanistic predicted vs. observed F and BS values throughout the study area extrapolated by lab experiments and literature search. The resulting relationship was reliable for both species, and body size and fecundity were highly correlated in M. galloprovincialis compared to B. pharaonis; FT-DEB showed correct predictions of presence in more than 75 % of sites, and the regression between BS predicted vs. observed was highly significant in both species. Whilst recognising the importance of biotic interactions in shaping the distribution of species, our FT-DEB approach provided reliable quantitative estimates of where our species had sufficient F to support local populations or suggesting reproductive failure. Mechanistically, estimating F and BS as key traits of species life history can also be addressed within a broader, scale-dependent context that surpasses the limitations related to correlative species distribution models. PMID- 26373560 TI - Increase of Antimyeloperoxidase Antineutrophil Cytoplasmic Antibody (ANCA) in Patients with Renal ANCA-associated Vasculitis: Association with Risk to Relapse. AB - OBJECTIVE: The diagnostic values of antiproteinase 3 and antimyeloperoxidase tests using antineutrophil cytoplasmic antibodies (ANCA) are well established. Our study determined whether an increase in ANCA level was a predictor of disease flareup. METHODS: Our study included 126 patients with ANCA-associated renal vasculitis treated at 9 nephrology centers in Japan. The relationship between increased ANCA levels and relapse was assessed using time-dependent multivariate Cox regression models adjusted for clinically relevant factors. The outcome of interest was the time from remission to first relapse. RESULTS: During the observation period [median 41 mos, interquartile range (IQR) 23-66 mos], 118 patients (95.8%) achieved remission at least once. After achieving remission, 34 patients relapsed (21.7%). Time-dependent multivariate Cox regression models revealed that lung involvement (adjusted HR 2.29, 95% CI 1.13-4.65, p = 0.022) and increased ANCA levels (adjusted HR 17.4, 95% CI 8.42-36.0, p < 0.001) were significantly associated with relapse. The median time from ANCA level increase to relapse was 0.6 months (IQR 0-2.1 mos). CONCLUSION: In our study, an increase in ANCA level during remission was associated with a risk of disease relapse. A rise in ANCA level may be useful for guiding treatment decisions in appropriate subsets of patients with ANCA-associated vasculitis. PMID- 26373561 TI - Increased Prevalence of Diastolic Heart Failure in Patients with Rheumatoid Arthritis Correlates with Active Disease, but Not with Treatment Type. AB - OBJECTIVE: Although heart failure (HF) is a major cause of premature mortality, there is little information regarding its prevalence and associated risk factors in patients with rheumatoid arthritis (RA). In this study, we evaluated the prevalence of HF in a community-based RA cohort. Further, we investigated the effect of RA activity and present treatment on HF rate and cardiac structure. METHODS: A diagnostic workup for HF according to the European Society of Cardiology recommendations was performed in 157 patients with RA fulfilling the American College of Rheumatology/European League Against Rheumatism criteria (68% women, age 61 +/- 13 yrs) from our outpatient clinic and in 77 age- and sex matched controls. RESULTS: The prevalence of HF in patients with RA (24%) was unexpectedly high and differed significantly from the control sample (6%, p = 0.001). Diastolic HF was the dominant type (23% vs 6%), and clinical symptoms alone were of low diagnostic value. Active RA (28-joint Disease Activity Score >= 2.6: OR 3.4, 95% CI 1.3-9.8) was an independent risk factor of HF, as well as systemic inflammation (erythrocyte sedimentation rate > 16 mm/h: OR 5.4, 95% CI 2.1-16; C-reactive protein > 10 mg/l: OR 2.6, 95% CI 0.8-8.0) and RA duration > 10 years (OR 2.6, 95% CI 1.2-5.8). HF in RA was associated with concentric hypertrophy (48% vs 17%, p < 0.001) and reduced longitudinal strain (-17.2% vs 19.7%, p < 0.001). However, the prevalence of HF was equivalent between the treatment groups [conventional synthetic disease-modifying antirheumatic drugs (DMARD) 25%, tumor necrosis factor inhibitors 22%, other biological DMARD 27%]. CONCLUSION: Recognition of all diastolic HF in RA requires a complex diagnostic approach. Active rather than inactive RA places patients at a higher risk for HF, whereas influence of RA treatment on HF risk needs to be elucidated in further studies. PMID- 26373562 TI - Current State of Reporting Pain Outcomes in Cochrane Reviews of Chronic Musculoskeletal Pain Conditions and Considerations for an OMERACT Research Agenda. AB - OBJECTIVE: To assess the current state of reporting of pain outcomes in Cochrane reviews on chronic musculoskeletal painful conditions and to elicit opinions of patients, healthcare practitioners, and methodologists on presenting pain outcomes to patients, clinicians, and policymakers. METHODS: We identified all reviews in the Cochrane Library of chronic musculoskeletal pain conditions from Cochrane review groups (Back, Musculoskeletal, and Pain, Palliative, and Supportive Care) that contained a summary of findings (SoF) table. We extracted data on reported pain domains and instruments and conducted a survey and interviews on considerations for SoF tables (e.g., pain domains, presentation of results). RESULTS: Fifty-seven SoF tables in 133 Cochrane reviews were eligible. SoF tables reported pain in 56/57, with all presenting results for pain intensity (20 different outcome instruments), pain interference in 8 SoF tables (5 different outcome instruments), and pain frequency in 1 multiple domain instrument. Other domains like pain quality or pain affect were not reported. From the survey and interviews [response rate 80% (36/45)], we derived 4 themes for a future research agenda: pain domains, considerations for assessing truth, discrimination, and feasibility; clinically important thresholds for responder analyses and presenting results; and establishing hierarchies of outcome instruments. CONCLUSION: There is a lack of standardization in the domains of pain selected and the manner that pain outcomes are reported in SoF tables, hampering efforts to synthesize evidence. Future research should focus on the themes identified, building partnerships to achieve consensus and develop guidance on best practices for reporting pain outcomes. PMID- 26373563 TI - Current Status, Goals, and Research Agenda for Outcome Measures Development in Behcet Syndrome: Report from OMERACT 2014. AB - OBJECTIVE: There is an unmet need for reliable, validated, and widely accepted outcomes and outcome measures for use in clinical trials in Behcet syndrome (BS). Our report summarizes initial steps taken by the Outcome Measures in Rheumatology (OMERACT) vasculitis working group toward developing a core set of outcome measures for BS according to the OMERACT methodology, including the OMERACT Filter 2.0, and discussions during the first meeting of the BS working group held during OMERACT 12 (2014). METHODS: During OMERACT 12, some of the important challenges in developing outcomes for BS were outlined and discussed, and a research agenda was drafted. RESULTS: Among topics discussed were the advantages and disadvantages of a composite measure for BS that evaluates several organs/organ systems; bringing patients and physicians together for discussions about how to assess disease activity; use of organ-specific measures developed for other diseases; and the inclusion of generic, disease-specific, or organ specific measures. The importance of incorporating patients' perspectives, concerns, and ideas into outcome measure development was emphasized. CONCLUSION: The planned research agenda includes conducting a Delphi exercise among physicians from different specialties that are involved in the care of patients with BS and among patients with BS, with the aim of identifying candidate domains and subdomains to be assessed in randomized clinical trials of BS, and candidate items for a composite measure. The ultimate goal of the group is to develop a validated and widely accepted core set of outcomes and outcome measures for use in clinical trials in BS. PMID- 26373564 TI - Inflammatory Bowel Disease in Juvenile Idiopathic Arthritis Patients Treated with Biologics. AB - OBJECTIVE: Evolving inflammatory bowel disease (IBD) is a matter of interest in patients with juvenile idiopathic arthritis (JIA) and might be associated with JIA therapy. METHODS: Data from the German biologics registry (Biologika in der Kinderrheumatologie; BiKeR) from 2001 to 2013 were analyzed. RESULTS: There were 3071 patients with 8389 patient-years (PY) of observation followed. IBD was diagnosed in 11 patients, 8 with Crohn disease and 3 with ulcerative colitis. IBD incidence in patients with JIA was 1.31/1000 PY and higher than published IBD incidences in pediatric populations. Compared with the total BiKeR cohort, patients with IBD more commonly had enthesitis-related arthritis, extended oligoarthritis, psoriatic arthritis, and also rheumatoid factor (RF)-negative polyarthritis. No IBD occurred in patients with systemic JIA or RF-positive polyarthritis. In patients treated with methotrexate (MTX), the IBD incidence was significantly lower compared with patients not treated with MTX. Etanercept (ETN) monotherapy, but not the combination of ETN and MTX, was associated with an increased incidence of IBD. CONCLUSION: Incidence of IBD in patients with JIA is higher than in the population. MTX turned out to be protective, even in combination with ETN. PMID- 26373565 TI - Psychiatric Disorders in Young Adults Diagnosed with Juvenile Fibromyalgia in Adolescence. AB - OBJECTIVE: Adolescents with juvenile-onset fibromyalgia (JFM) have increased rates of psychiatric disorders, but to our knowledge no studies have examined psychiatric disorders in adolescents with JFM when they enter young adulthood. This study examined the prevalence of psychiatric disorders in young adults diagnosed with JFM during adolescence and the relationship between mental health diagnoses and physical functioning. METHODS: Ninety-one young adults (mean age 21.60, SD 1.96) with a history of JFM being followed as part of a prospective longitudinal study and 30 matched healthy controls (mean age 21.57, SD 1.55) completed a structured interview of psychiatric diagnoses and a self-report measure of physical impairment. RESULTS: Young adults with a history of JFM were more likely to have current and lifetime histories of anxiety disorders (70.3% and 76.9%, respectively) compared with controls (33.3% for both, both p < 0.001). Individuals with JFM were also more likely to have current and lifetime histories of major mood disorders (29.7% and 76.9%, respectively) compared with controls (10% and 40%, p < 0.05). The presence of a current major mood disorder was significantly related to impairment in physical functioning [F (1, 89) = 8.30, p < 0.01] and role limitations attributable to a physical condition [F (1, 89) = 7.09, p < 0.01]. CONCLUSION: Psychiatric disorders are prevalent in young adulthood for individuals with a history of JFM, and a current major mood disorder is associated with greater physical impairment. Greater attention to early identification and treatment of mood disorders in patients with JFM is warranted. PMID- 26373566 TI - Comparison of Lupus Nephritis Induction Treatments in a Hispanic Population: A Single-center Cohort Analysis. AB - OBJECTIVE: To evaluate response rates in an adult lupus nephritis (LN) cohort in Mexico City, Mexico. METHODS: We analyzed 165 patients with biopsy-proven LN histological International Society of Nephrology/Renal Pathology Society classes III, IV, or V, distributed by treatment drug in 3 groups: mycophenolate mofetil (MMF; dosage > 2 g/day per 6 mos, n = 63), intravenous cyclophosphamide (IVC; 0.7 g/m(2) body surface area monthly per 6 pulses, n = 66), or azathioprine (AZA; dosage > 1.5 mg/kg/day per 6 mos, n = 36). Median followup was 31 +/- 18 months. The primary endpoint was the proportion of patients achieving complete renal response (CR). Secondary endpoints included the proportion of patients achieving renal response (complete or partial), renal flare-free survival, doubling of serum creatinine, and progression to endstage renal disease (ESRD). RESULTS: MMF induction was superior to IVC (HR 2.00, 95% CI 1.23-3.25, p = 0.005) and AZA (HR 2.12, 95% CI 1.23-3.66, p = 0.007) in the primary endpoint. Censored CR rates at 6, 12, 24, and 36 months were 32.6%, 56.1%, 76.6%, and 94.1% for MMF; 24.2%, 34.4%, 57.9%, and 62.1% for IVC; and 8.4%, 39.8%, 49.7%, and 49.7% for AZA. MMF was also superior in renal response to treatment and renal flare-free survival outcomes. There were no differences between groups in doubling of serum creatinine or progression to ESRD. The induction treatment with MMF (HR 2.04, 95% CI 1.25-3.33, p = 0.005) and absence of vascular lesions on renal biopsy (HR 2.05, 95% CI 1.25-3.37, p = 0.004) were associated with CR, whereas proteinuria at the time of presentation was negatively associated with CR (HR 0.91, 95% CI 0.84-0.98, p = 0.013). CONCLUSION: MMF induction therapy is superior to IVC and AZA in patients with LN of Mexican-mestizo race. PMID- 26373567 TI - A Call for Evidence-based Decision Making When Selecting Outcome Measurement Instruments for Summary of Findings Tables in Systematic Reviews: Results from an OMERACT Working Group. AB - OBJECTIVE: Systematic reviews often struggle with how to combine information when more than 1 instrument is used across studies being synthesized. Different techniques have been suggested based on frequency of use in the literature, or on consensus. We explore an approach blending 2 initiatives: OMERACT (Outcome Measurement in Rheumatology) and COSMIN (Consensus On Selection of Measurement Instruments), and investigate the effects of an evidence-based measurement approach on selection of outcomes. METHODS: Readings were circulated to attendees registered for a preconference workshop on pain measurement. Three instruments were considered and exercises conducted to engage people in the content and measurement performance of these tools. Consensus was sought that an evidence based approach could be created for selection of instruments for summary of findings (SoF) tables. RESULTS: The blending of COSMIN and OMERACT approaches led to an evidence-based approach that depended both on a clear definition of target concept and a review of measurement performance of the instrument. Participants emphasized that conceptual clarity and practical considerations should come before measurement property results. CONCLUSION: Evidence-based approaches can be adopted for selection of instruments for SoF tables. A research agenda was formulated. PMID- 26373568 TI - Glucagon receptor antagonism induces increased cholesterol absorption. AB - Glucagon and insulin have opposing action in governing glucose homeostasis. In type 2 diabetes mellitus (T2DM), plasma glucagon is characteristically elevated, contributing to increased gluconeogenesis and hyperglycemia. Therefore, glucagon receptor (GCGR) antagonism has been proposed as a pharmacologic approach to treat T2DM. In support of this concept, a potent small-molecule GCGR antagonist (GRA), MK-0893, demonstrated dose-dependent efficacy to reduce hyperglycemia, with an HbA1c reduction of 1.5% at the 80 mg dose for 12 weeks in T2DM. However, GRA treatment was associated with dose-dependent elevation of plasma LDL-cholesterol (LDL-c). The current studies investigated the cause for increased LDL-c. We report findings that link MK-0893 with increased glucagon-like peptide 2 and cholesterol absorption. There was not, however, a GRA-related modulation of cholesterol synthesis. These findings were replicated using structurally diverse GRAs. To examine potential pharmacologic mitigation, coadministration of ezetimibe (a potent inhibitor of cholesterol absorption) in mice abrogated the GRA-associated increase of LDL-c. Although the molecular mechanism is unknown, our results provide a novel finding by which glucagon and, hence, GCGR antagonism govern cholesterol metabolism. PMID- 26373569 TI - Efficacy of octreotide long-acting repeatable in neuroendocrine tumors: RADIANT-2 placebo arm post hoc analysis. AB - Somatostatin analogues (SSA) have demonstrated antiproliferative activity in addition to efficacy for carcinoid symptom control in functional neuroendocrine tumors (NET). A post hoc analysis of the placebo arm of the RAD001 In Advanced Neuroendocrine Tumors-2 (RADIANT-2) study was conducted to assess the efficacy of octreotide long-acting repeatable (LAR) on progression-free survival (PFS) and overall survival (OS) estimated using the Kaplan-Meier method. Out of 213 patients randomized to placebo plus octreotide LAR in RADIANT-2, 196 patients with foregut, midgut, or hindgut NET were considered for present analysis. Of these, 41 patients were SSA-treatment naive and 155 had received SSA therapy before study entry. For SSA-naive patients, median PFS by adjudicated central review was 13.6 (95% CI 8.2-22.7) months. For SSA-naive patients with midgut NET (n=24), median PFS was 22.2 (95% CI 8.3-29.5) months. For patients who had received SSA previously, the median PFS was 11.1 (95% CI 8.4-14.3) months. Among the SSA-pretreated patients who had midgut NET (n=119), the median PFS was 12.0 (95% CI 8.4-19.3) months. Median OS was 35.8 (95% CI 32.5-48.9) months for patients in the placebo plus octreotide LAR arm; 50.6 (36.4 - not reached) months for SSA-naive patients and 33.5 (95% CI 27.5-44.7) months for those who had received prior SSA. This post hoc analysis of the placebo arm of the large phase 3 RADIANT-2 study provides data on PFS and OS among patients with progressive NET treated with octreotide therapy. PMID- 26373571 TI - The role of reproductive hormones in epithelial ovarian carcinogenesis. AB - Epithelial ovarian cancer comprises ~85% of all ovarian cancer cases. Despite acceptance regarding the influence of reproductive hormones on ovarian cancer risk and considerable advances in the understanding of epithelial ovarian carcinogenesis on a molecular level, complete understanding of the biologic processes underlying malignant transformation of ovarian surface epithelium is lacking. Various hypotheses have been proposed over the past several decades to explain the etiology of the disease. The role of reproductive hormones in epithelial ovarian carcinogenesis remains a key topic of research. Primary questions in the field of ovarian cancer biology center on its developmental cell of origin, the positive and negative effects of each class of hormones on ovarian cancer initiation and progression, and the role of the immune system in the ovarian cancer microenvironment. The development of the female reproductive tract is dictated by the hormonal milieu during embryogenesis. Intensive research efforts have revealed that ovarian cancer is a heterogenous disease that may develop from multiple extra-ovarian tissues, including both Mullerian (fallopian tubes, endometrium) and non-Mullerian structures (gastrointestinal tissue), contributing to its heterogeneity and distinct histologic subtypes. The mechanism underlying ovarian localization, however, remains unclear. Here, we discuss the role of reproductive hormones in influencing the immune system and tipping the balance against or in favor of developing ovarian cancer. We comment on animal models that are critical for experimentally validating existing hypotheses in key areas of endocrine research and useful for preclinical drug development. Finally, we address emerging therapeutic trends directed against ovarian cancer. PMID- 26373572 TI - Activin Receptor-like Kinase 1 Ligand Trap Reduces Microvascular Density and Improves Chemotherapy Efficiency to Various Solid Tumors. AB - PURPOSE: Antiangiogenic therapy, mostly targeting VEGF, has been applied in cancer patients for the last decade. However, resistance to anti-VEGF therapy and/or no significant benefit as monotherapeutic agent is often observed. Therefore, new antiangiogenic strategies are needed. In the current study, we investigated the therapeutic effect of interfering with the bone morphogenetic protein (BMP)9/activin receptor-like kinase (ALK)1 signaling pathway by using an ALK1-Fc ligand trap. EXPERIMENTAL DESIGN: We analyzed the potential antiangiogenic and antitumor effects of ALK1-Fc protein as monotherapy and in combination with chemotherapy in vivo in mouse models of melanoma, head and neck cancer, and invasive lobular breast carcinomas. ALK1-Fc sequesters BMP9 and 10 and prevents binding of these ligands to endothelial ALK1, which regulates angiogenesis. RESULTS: Treatment of mice with ALK1-Fc strongly decreased the tumors' microvascular density in the three different mouse cancer models. However, this effect was not accompanied by a reduction in tumor volume. An immunohistochemical analysis of the tumor samples revealed that ALK1-Fc treatment increased the pericyte coverage of the remaining tumor vessels and decreased the hypoxia within the tumor. Next, we observed that combining ALK1-Fc with cisplatin inhibited tumor growth in the breast and head and neck cancer models more efficiently than chemotherapy alone. CONCLUSIONS: The addition of ALK1-Fc to the cisplatin treatment was able to enhance the cytotoxic effect of the chemotherapy. Our results provide strong rationale to explore combined targeting of ALK1 with chemotherapy in a clinical setting, especially in the ongoing phase II clinical trials with ALK1-Fc. PMID- 26373574 TI - The FGFR Landscape in Cancer: Analysis of 4,853 Tumors by Next-Generation Sequencing. AB - PURPOSE: Molecular profiling may have prognostic and predictive value, and is increasingly used in the clinical setting. There are more than a dozen fibroblast growth factor receptor (FGFR) inhibitors in development. Optimal therapeutic application of FGFR inhibitors requires knowledge of the rates and types of FGFR aberrations in a variety of cancer types. EXPERIMENTAL DESIGN: We analyzed frequencies of FGFR aberrations in 4,853 solid tumors that were, on physician request, tested in a Clinical Laboratory Improvement Amendments (CLIA) laboratory (Foundation Medicine) using next-generation sequencing (182 or 236 genes), and analyzed by N-of-One. RESULTS: FGFR aberrations were found in 7.1% of cancers, with the majority being gene amplification (66% of the aberrations), followed by mutations (26%) and rearrangements (8%). FGFR1 (mostly amplification) was affected in 3.5% of 4,853 patients; FGFR2 in 1.5%; FGFR3 in 2.0%; and FGFR4 in 0.5%. Almost every type of malignancy examined showed some patients with FGFR aberrations, but the cancers most commonly affected were urothelial (32% FGFR aberrant); breast (18%); endometrial (~13%), squamous lung cancers (~13%), and ovarian cancer (~9%). Among 35 unique FGFR mutations seen in this dataset, all but two are found in COSMIC. Seventeen of the 35 are known to be activating, and 11 are transforming. CONCLUSIONS: FGFR aberrations are common in a wide variety of cancers, with the majority being gene amplifications or activating mutations. These data suggest that FGFR inhibition could be an important therapeutic option across multiple tumor types. PMID- 26373573 TI - Molecular Pathways: Targeting the Stimulator of Interferon Genes (STING) in the Immunotherapy of Cancer. AB - Novel immunotherapy approaches are transforming the treatment of cancer, yet many patients remain refractory to these agents. One hypothesis is that immunotherapy fails because of a tumor microenvironment that fails to support recruitment of immune cells, including CD8(+) T cells. Therefore, new approaches designed to initiate a de novo antitumor immune response from within the tumor microenvironment are being pursued. Recent evidence has indicated that spontaneous activation of the Stimulator of Interferon Genes (STING) pathway within tumor-resident dendritic cells leads to type I IFN production and adaptive immune responses against tumors. This pathway is activated in the presence of cytosolic DNA that is detected by the sensor cyclic GMP-AMP synthase (cGAS) and generates cyclic GMP-AMP (cGAMP), which binds and activates STING. As a therapeutic approach, intratumoral injection of STING agonists has demonstrated profound therapeutic effects in multiple mouse tumor models, including melanoma, colon, breast, prostate, and fibrosarcoma. Better characterization of the STING pathway in human tumor recognition, and the development of new pharmacologic approaches to engage this pathway within the tumor microenvironment in patients, are important areas for clinical translation. PMID- 26373570 TI - Obesity and cancer: mechanistic insights from transdisciplinary studies. AB - Obesity is associated with a range of health outcomes that are of clinical and public health significance, including cancer. Herein, we summarize epidemiologic and preclinical evidence for an association between obesity and increased risk of breast and prostate cancer incidence and mortality. Moreover, we describe data from observational studies of weight change in humans and from calorie restriction studies in mouse models that support a potential role for weight loss in counteracting tumor-promoting properties of obesity in breast and prostate cancers. Given that weight loss is challenging to achieve and maintain, we also consider evidence linking treatments for obesity-associated co-morbidities, including metformin, statins and non-steroidal anti-inflammatory drugs, with reduced breast and prostate cancer incidence and mortality. Finally, we highlight several challenges that should be considered when conducting epidemiologic and preclinical research in the area of obesity and cancer, including the measurement of obesity in population-based studies, the timing of obesity and weight change in relation to tumor latency and cancer diagnosis, and the heterogeneous nature of obesity and its associated co-morbidities. Given that obesity is a complex trait, comprised of behavioral, epidemiologic and molecular/metabolic factors, we argue that a transdisciplinary approach is the key to understanding the mechanisms linking obesity and cancer. As such, this review highlights the critical need to integrate evidence from both epidemiologic and preclinical studies to gain insight into both biologic and non-biologic mechanisms contributing to the obesity-cancer link. PMID- 26373576 TI - Composition and Tissue-Specific Distribution of Stilbenoids in Grape Canes Are Affected by Downy Mildew Pressure in the Vineyard. AB - Grape canes are byproducts of viticulture containing valuable bioactive stilbenoids including monomers and oligomers of E-resveratrol. Although effective contents in stilbenoids are known to be highly variable, the determining factors influencing this composition remain poorly understood. As stilbenoids are locally induced defense compounds in response to phytopathogens, this study assessed the impact of downy mildew infection during the growing season on the stilbenoid composition of winter-harvested grape canes. The spatial distribution between pith, conducting tissues, and cortex of E-piceatannol, E-resveratrol, E-epsilon viniferin, ampelopsin A, E-miyabenol C, Z/E-vitisin B, hopeaphenol, and isohopeaphenol in grape canes from infected vineyards was strongly altered. In conducting tissues, representing the main site of stilbenoid accumulation, E epsilon-viniferin content was higher and E-resveratrol content was lower. These findings suppose that the health status in vineyards could modify the composition of stilbenoids in winter-harvested grape canes and subsequently the potential biological properties of the valuable extracts. PMID- 26373577 TI - The occurrence of Echinorhynchus salmonis Muller, 1784 in benthic amphipods in the Baltic Sea. AB - The acanthocephalan Echinorhynchus salmonis Muller, 1784 is a common parasite of salmonid fish, but it has rarely been reported from an intermediate host. Samples of benthic amphipods, Monoporeia affinis (Lindstrom), were taken from multiple, deep sites (usually below 70 m) in the Gulf of Bothnia over the course of more than a decade and examined for acanthocephalans. Overall, only 0.44% of 23 296 amphipods were infected, all with just a single worm. This prevalence is consistent with several previous reports of acanthocephalans in deep-water, benthic amphipods, but it appears low compared to that often reported for acanthocephalan species infecting littoral amphipods. Parasite occurrence did not exhibit a clear regional pattern (i.e. northern vs southern sites) nor did it have any relationship with site depth. At sites sampled over multiple years, parasite abundance was consistently low (mostly < 0.01), though two spikes in abundance (over 0.06) were also observed, indicating that infection can be substantially higher at particular times or in particular places. The median density of E. salmonis in samples containing the parasite was estimated as 8.4 cystacanths per m(2). PMID- 26373575 TI - PD-L1 and HLA Class I Antigen Expression and Clinical Course of the Disease in Intrahepatic Cholangiocarcinoma. AB - PURPOSE: More effective therapy is needed for intrahepatic cholangiocarcinoma (ICC). The encouraging clinical results obtained with checkpoint molecule specific monoclonal antibodies (mAb) have prompted us to investigate whether this type of immunotherapy may be applicable to ICC. The aims of this study were to determine whether (i) patients mount a T-cell immune response to their ICC, (ii) checkpoint molecules are expressed on both T cells and tumor cells, and (iii) tumor cells are susceptible to recognition by cognate T cells. EXPERIMENTAL DESIGN: Twenty-seven ICC tumors were analyzed for (i) lymphocyte infiltrate, (ii) HLA class I and HLA class II expression, and (iii) PD-1 and PD-L1 expression by T cells and ICC cells, respectively. The results of this analysis were correlated with the clinicopathologic characteristics of the patients investigated. RESULTS: Lymphocyte infiltrates were identified in all tumors. PD-L1 expression and HLA class I antigen expression by ICC cells was observed in 8 and 11, respectively, of the 27 tumors analyzed. HLA class I antigen expression correlated with CD8(+) T-cell infiltrate. Furthermore, positive HLA class I antigen expression in combination with negative/rare PD-L1 expression was associated with favorable clinical course of the disease. CONCLUSIONS: ICC patients are likely to mount a T cell immune response against their own tumors. Defects in HLA class I antigen expression in combination with PD-L1 expression by ICC cells provide them with an immune escape mechanism. This mechanism justifies the implementation of immunotherapy with checkpoint molecule-specific mAbs in patients bearing ICC tumors without defects in HLA class I antigen expression. PMID- 26373578 TI - Arcanobacterium pinnipediorum sp. nov., isolated from a harbour seal. AB - A polyphasic taxonomic study was performed on an unidentified Arcanobacterium like, Gram-stain-positive bacterium, strain 2710T, isolated from a harbour seal. Comparative 16S rRNA gene sequence analysis showed that this bacterial strain belonged to the genus Arcanobacterium and was related most closely to the type strains of Arcanobacterium phocae (98.4 % similarity) and Arcanobacterium phocisimile (97.5 %). 16S rRNA gene sequence similarities to the type strains of other Arcanobacterium species were between 95.3 and 96.9 %. DNA-DNA hybridization values between strain 2710T and A. phocae DSM 10002T and A. phocisimile LMG 27073T were 4.7 % (reciprocal 56 %) and 23 % (reciprocal 7.7 %), respectively. The presence of the major menaquinone MK-9(H4) and a polar lipid profile with the major compounds diphosphatidylglycerol, phosphatidylinositol and phosphatidylinositol mannoside supported the affiliation of strain 2710T to the genus Arcanobacterium. The major fatty acids were C16:0, C18:1omega9c, C18:0 and C18:2omega6,9c/anteiso-C18:0. The peptidoglycan structure was of cross-linkage type A5alpha (l-Lys-l-Lys-d-Glu). Physiological and biochemical tests clearly distinguished the isolate from other members of the genus Arcanobacterium. Based on these tests, it is proposed that this unknown bacterium should be classified as a novel species of the genus Arcanobacterium, with the name Arcanobacterium pinnipediorum sp. nov. The type strain is 2710T ( = DSM 28752T = LMG 28298T). PMID- 26373579 TI - Intra-Bone Marrow Transplantation of Endosteal Bone Marrow Cells Facilitates Allogeneic Hematopoietic and Stromal Cells Engraftment Dependent on Early Expression of CXCL-12. AB - BACKGROUND: Hematopoietic stem cell transplantation (HSCT) has been considered as an effective approach at inducing allogeneic hematopoietic reconstitution and immune tolerance. However, it remains critical to find the optimal HSCT delivery method and robust sources of hematopoietic stem cells (HSCs). MATERIAL AND METHODS: We introduced a new method by infusing allogeneic endosteal bone marrow cells (BMCs) harvested from long bones endosteum through intra-bone marrow transplantation (IBBMT) into irradiated mice. Recipient mice that were transplanted with central BMCs or through intravenous bone marrow transplantation (IVBMT) were used as controls (n=6 per group). We compared the new method with each control group for allogeneic HSCs homing pattern, peripheral blood chimerism level, skin allograft survival time, and donor stromal cell percentage in recipient BM. AMD3100 was injected to determine whether chemokine stromal cell derived factor-1 (CXCL-12) was critical for the new method. RESULTS: More allogeneic HSCs homed into spleen and bone marrow for the new method as compared to each control group. IBBMT of endosteal BMCs led to a higher peripheral blood chimerism and skin allograft survival. At 18 weeks, donor stromal cell percentage in recipient BMCs was higher for the new method than in each control group. By AMD3100 blockade at day 1, peripheral blood chimerism level and donor stromal cell percentage were significantly reduced as compared to the control group without AMD3100 blockade. CONCLUSIONS: Our study suggests that IBBMT of endosteal BMCs is an effective approach for HSCT in inducing allogeneic hematopoietic reconstitution. The advantage is dependent upon the early expression of CXCL-12 after bone marrow transplantation. PMID- 26373580 TI - Free Shiga toxin 1-encoding bacteriophages are less prevalent than Shiga toxin 2 phages in extraintestinal environments. AB - Stx bacteriophages are involved in the pathogenicity of Stx-producing Escherichia coli. Induction of the Stx phage lytic cycle increases Stx expression and releases Stx phages that reach extracellular environments. Stx phage family comprises different phages that harbour any stx subtype. Stx2 is closely related with severe disease and therefore previous studies focused on free Stx2 phages in extraintestinal environments. To provide similar information regarding Stx1 phages, we evaluate free Stx1 phages in 357 samples of human and animal wastewater, faeces, river water, soil, sludge and food. Our method, based on quantification of stx1 in the DNA from the viral fraction, was validated using electron microscopy counting of phages and infectivity. The overall prevalence of Stx1 phages was very low: 7.6% of positive samples and values below 3 * 10(3) GC (gene copies) ml(-1) . These results contrast starkly with the abundance of Stx2 phages in the samples (68.4%). This environmental scarcity of free Stx1 phages is attributed to their lower rates of induction and the fact that Stx1 does not require phage induction to be expressed because it possesses an independent promoter. The implications of the low prevalence of free Stx1 phages for the emergence of new pathogenic strains in the environment are discussed. PMID- 26373582 TI - Understanding skill acquisition among registered nurses: the 'perpetual novice' phenomenon. AB - AIMS AND OBJECTIVES: To determine whether the perpetual novice phenomenon exists beyond nephrology nursing where it was first described. BACKGROUND: The perpetual novice is a state in which nurses are unable to progress from a novice to an expert in one or more essential clinical skills which are used in their practice area. Maintaining clinical competence is essential to quality patient care outcomes. DESIGN: An exploratory, sequential, mixed methods design was used, comprised of a quantitative component followed by in-depth interviews. METHODS: Registered nurses employed in one of four roles were recruited from two university-affiliated hospitals in London, Ontario, Canada: Clinical Educator, Clinical Nurse Specialist, Advanced Practice Nurse and Nurse Practitioner. Participants were first asked to complete and return a survey and demographic questionnaire. Following the return of the completed surveys, ten participants were interviewed to enhance the results of the surveys. RESULTS: The results of the surveys confirmed that the perpetual novice phenomenon exists across multiple nursing care areas. Four contributing factors, both personal and structural in nature, emerged from the interviews: (1) opportunities for education, (2) the context of learning, (3) personal motivation and initiative to learn and (4) the culture of the units where nurses worked. CONCLUSION: The perpetual novice phenomenon exists due to a combination of both personal factors as well as contextual factors in the work environment. RELEVANCE TO CLINICAL PRACTICE: The results assist in directing future educational interventions and provide nursing leaders with the information necessary to create work environments that best enable practicing nurses to acquire and maintain clinical competence. PMID- 26373584 TI - Correction to "Thermally Activated Delayed Fluorescence Sensitized Phosphorescence: A Strategy To Break the Trade-Off between Efficiency and Efficiency Roll-Off". PMID- 26373583 TI - REDV Peptide Conjugated Nanoparticles/pZNF580 Complexes for Actively Targeting Human Vascular Endothelial Cells. AB - Herein, we demonstrate that the REDV peptide modified nanoparticles (NPs) can serve as a kind of active targeting gene carrier to condensate pZNF580 for specific promotion of the proliferation of endothelial cells (ECs). First, we synthesized a series of biodegradable amphiphilic copolymers by ring-opening polymerization reaction and graft modification with REDV peptide. Second, we prepared active targeting NPs via self-assembly of the amphiphilic copolymers using nanoprecipitation technology. After condensation with negatively charged pZNF580, the REDV peptide modified NPs/pZNF580 complexes were formed finally. Due to the binding affinity toward ECs of the specific peptide, these REDV peptide modified NPs/pZNF580 complexes could be recognized and adhered specifically by ECs in the coculture system of ECs and human artery smooth muscle cells (SMCs) in vitro. After expression of ZNF580, as the key protein to promote the proliferation of ECs, the relative ZNF580 protein level increased from 15.7% to 34.8%. The specificity in actively targeting ECs of the REDV peptide conjugated NPs/pZNF580 complexes was still retained in the coculture system. These findings in the present study could facilitate the development of actively targeting gene carriers for the endothelialization of artificial blood vessels. PMID- 26373585 TI - The psychological factor 'self-blame' predicts overuse injury among top-level Swedish track and field athletes: a 12-month cohort study. AB - BACKGROUND: Athletes' psychological characteristics are important for understanding sports injury mechanisms. We examined the relevance of psychological factors in an integrated model of overuse injury risk in athletics/track and field. METHODS: Swedish track and field athletes (n=278) entering a 12-month injury surveillance in March 2009 were also invited to complete a psychological survey. Simple Cox proportional hazards models were compiled for single explanatory variables. We also tested multiple models for 3 explanatory variable groupings: an epidemiological model without psychological variables, a psychological model excluding epidemiological variables and an integrated (combined) model. RESULTS: The integrated multiple model included the maladaptive coping behaviour self-blame (p=0.007; HR 1.32; 95% CI 1.08 to 1.61), and an interaction between athlete category and injury history (p<0.001). Youth female (p=0.034; HR 0.51; 95% CI 0.27 to 0.95) and youth male (p=0.047; HR 0.49; 95% CI 0.24 to 0.99) athletes with no severe injury the previous year were at half the risk of sustaining a new injury compared with the reference group. A training load index entered the epidemiological multiple model, but not the integrated model. CONCLUSIONS: The coping behaviour self-blame replaced training load in an integrated explanatory model of overuse injury risk in athletes. What seemed to be more strongly related to the likelihood of overuse injury was not the athletics load per se, but, rather, the load applied in situations when the athlete's body was in need of rest. PMID- 26373588 TI - 28 degrees Congresso Nazionale AINR Napoli - 16-18 settembre 2015. PMID- 26373586 TI - Defining the practice of pancreatoduodenectomy around the world. AB - BACKGROUND: Pancreatoduodenectomy (PD) is a technically challenging operation characterized by numerous management decisions. OBJECTIVE: This study was designed to test the hypothesis that there is significant variation in the contemporary global practice of PD. METHODS: A survey with native-language translation was distributed to members of 22 international gastrointestinal surgical societies. Practice patterns and surgical decision making for PD were assessed. Regions were categorized as North America, South/Central America, Asia/Australia, and Europe/Africa/Middle East. RESULTS: Surveys were completed by 897 surgeons, representing six continents and eight languages. The median age and length of experience of respondents were 45 years and 13 years, respectively. In 2013, surgeons performed a median of 12 PDs and reported a median career total of 80 PDs; only 53.8% of respondents had surpassed the number of PDs considered necessary to surmount the learning curve (>60). Significant regional differences were observed in annual and career PD volumes (P < 0.001). Only 3.7% of respondents practised pancreas surgery exclusively, but 54.8% performed only hepatopancreatobiliary surgery. Worldwide, the preferred form of anastomotic reconstruction was pancreatojejunostomy (88.7%). Regional variability was evident in terms of anastomotic/suture technique, stent use and drain use (including type and number), as well as in the use of octreotide, sealants and autologous patches (P < 0.02 for all). CONCLUSIONS: Globally, there is significant variability in the practice of PD. Many of these choices contrast with established randomized evidence and may contribute to variance in outcomes. PMID- 26373587 TI - Benvenuti a Napoli. PMID- 26373589 TI - I Congressi Nazionali AINR. PMID- 26373590 TI - Relatori e Moderatori 28 degrees Congresso Nazionale AINR. PMID- 26373591 TI - Programma scientifico. PMID- 26373592 TI - 16 SETTEMBRE 2015 - Sala Vesuvio - ore 15:30 - 17:00 DISCUTIAMONE INSIEME: PRESENTAZIONE DI CASI CLINICI. PMID- 26373593 TI - 17 Settembre 2015 - Auditorium - ore 08:30 - 10:30. PMID- 26373594 TI - 17 Settembre 2015 - Auditorium - ore 15:30 - 17:15. PMID- 26373595 TI - 17 Settembre 2015 - Sala Vesuvio - ore 08:30 - 10:30. PMID- 26373596 TI - 17 Settembre 2015 - Sala Vesuvio - ore 15:30 - 17:15 Comunicazioni Libere: Interventistica. PMID- 26373598 TI - Transport and retention of engineered Al2O3, TiO2, and SiO2 nanoparticles through various sedimentary rocks. AB - Engineered aluminum oxide (Al2O3), titanium dioxide (TiO2), and silicon dioxide (SiO2) nanoparticles (NPs) are utilized in a broad range of applications; causing noticeable quantities of these materials to be released into the environment. Issues of how and where these particles are distributed into the subsurface aquatic environment remain as major challenges for those in environmental engineering. In this study, transport and retention of Al2O3, TiO2, and SiO2 NPs through various saturated porous media were investigated. Vertical columns were packed with quartz-sand, limestone, and dolomite grains. The NPs were introduced as a pulse suspended in aqueous solutions and breakthrough curves in the column outlet were generated using an ultraviolet-visible spectrophotometer. It was found that Al2O3 and TiO2 NPs are easily transported through limestone and dolomite porous media whereas NPs recoveries were achieved two times higher than those found in the quartz-sand. The highest and lowest SiO2-NPs recoveries were also achieved from the quartz-sand and limestone columns, respectively. The experimental results closely replicated the general trends predicted by the filtration and DLVO calculations. Overall, NPs mobility through a porous medium was found to be strongly dependent on NP surface charge, NP suspension stability against deposition, and porous medium surface charge and roughness. PMID- 26373599 TI - Transition metal-mediated donor-acceptor coordination of low-oxidation state Group 14 element halides. AB - The reactivity of tungsten carbonyl adducts of Group 14 element (Ge, Sn and Pb) dihalides towards the metal-based donors (eta(5)-C5H5)Rh(PMe2Ph)2 and Pt(PCy3)2 was examined. When (eta(5)-C5H5)Rh(PMe2Ph)2 was treated with the Lewis acid supported Ge(ii) complex, THF.GeCl2.W(CO)5, cyclopentadienyl ring activation occurred, whereas the analogous Lewis acidic units SnCl2.W(CO)5 and PbCl2 form direct adducts with the Rh complex to yield Rh-Sn and Rh-Pb dative bonds. Attempts to prepare metal coordinated element(ii) hydrides by adding hydride sources to the above mentioned rhodium-E(ii) halide complexes were unsuccessful; in each case insoluble products were formed along with regeneration of free (eta(5)-C5H5)Rh(PMe2Ph)2. In a parallel study, ECl2.W(CO)5 (E = Ge or Sn) groups were shown to participate in E-Cl oxidation addition chemistry with (Cy3P)2Pt to give the formal Pt(ii) complexes ClPt(PCy3)2ECl.W(CO)5. PMID- 26373601 TI - Epileptogenic effects of NMDAR antibodies in a passive transfer mouse model. AB - Most patients with N-methyl D-aspartate-receptor antibody encephalitis develop seizures but the epileptogenicity of the antibodies has not been investigated in vivo. Wireless electroencephalogram transmitters were implanted into 23 C57BL/6 mice before left lateral ventricle injection of antibody-positive (test) or healthy (control) immunoglobulin G. Mice were challenged 48 h later with a subthreshold dose (40 mg/kg) of the chemo-convulsant pentylenetetrazol and events recorded over 1 h. Seizures were assessed by video observation of each animal and the electroencephalogram by an automated seizure detection programme. No spontaneous seizures were seen with the antibody injections. However, after the pro-convulsant, the test mice (n = 9) had increased numbers of observed convulsive seizures (P = 0.004), a higher total seizure score (P = 0.003), and a higher number of epileptic 'spike' events (P = 0.023) than the control mice (n = 6). At post-mortem, surprisingly, the total number of N-methyl D-aspartate receptors did not differ between test and control mice, but in test mice the levels of immunoglobulin G bound to the left hippocampus were higher (P < 0.0001) and the level of bound immunoglobulin G correlated with the seizure scores (R(2) = 0.8, P = 0.04, n = 5). Our findings demonstrate the epileptogenicity of N methyl D-aspartate receptor antibodies in vivo, and suggest that binding of immunoglobulin G either reduced synaptic localization of N-methyl D-aspartate receptors, or had a direct effect on receptor function, which could be responsible for seizure susceptibility in this acute short-term model. PMID- 26373602 TI - Manic episodes are related to changes in frontal cortex: a longitudinal neuroimaging study of bipolar disorder 1. AB - Higher numbers of manic episodes in bipolar patients has, in cross-sectional studies, been associated with less grey matter volume in prefrontal brain areas. Longitudinal studies are needed to determine if manic episodes set off progressive cortical changes, or if the association is better explained by premorbid brain conditions that increase risk for mania. We followed patients with bipolar disorder type 1 for 6 years. Structural brain magnetic resonance imaging scans were performed at baseline and follow-up. We compared patients who had at least one manic episode between baseline and follow-up (Mania group, n = 13) with those who had no manic episodes (No-Mania group, n = 18). We used measures of cortical volume, thickness, and area to assess grey matter changes between baseline and follow-up. We found significantly decreased frontal cortical volume (dorsolateral prefrontal and inferior frontal cortex) in the Mania group, but no volume changes in the No-Mania group. Our results indicate that volume decrease in frontal brain regions can be attributed to the incidence of manic episodes. PMID- 26373604 TI - Network dysfunction of emotional and cognitive processes in those at genetic risk of bipolar disorder. AB - The emotional and cognitive vulnerabilities that precede the development of bipolar disorder are poorly understood. The inferior frontal gyrus-a key cortical hub for the integration of cognitive and emotional processes-exhibits both structural and functional changes in bipolar disorder, and is also functionally impaired in unaffected first-degree relatives, showing diminished engagement during inhibition of threat-related emotional stimuli. We hypothesized that this functional impairment of the inferior frontal gyrus in those at genetic risk of bipolar disorder reflects the dysfunction of broader network dynamics underlying the coordination of emotion perception and cognitive control. To test this, we studied effective connectivity in functional magnetic resonance imaging data acquired from 41 first-degree relatives of patients with bipolar disorder, 45 matched healthy controls and 55 participants with established bipolar disorder. Dynamic causal modelling was used to model the neuronal interaction between key regions associated with fear perception (the anterior cingulate), inhibition (the left dorsolateral prefrontal cortex) and the region upon which these influences converge, namely the inferior frontal gyrus. Network models that embodied non linear, hierarchical relationships were the most strongly supported by data from our healthy control and bipolar participants. We observed a marked difference in the hierarchical influence of the anterior cingulate on the effective connectivity from the dorsolateral prefrontal cortex to the inferior frontal gyrus that is unique to the at-risk cohort. Non-specific, non-hierarchical mechanisms appear to compensate for this network disturbance. We thus establish a specific network disturbance suggesting dysfunction in the processes that support hierarchical relationships between emotion and cognitive control in those at high genetic risk for bipolar disorder. PMID- 26373603 TI - Serotonergic signalling suppresses ataxin 3 aggregation and neurotoxicity in animal models of Machado-Joseph disease. AB - Polyglutamine diseases are a class of dominantly inherited neurodegenerative disorders for which there is no effective treatment. Here we provide evidence that activation of serotonergic signalling is beneficial in animal models of Machado-Joseph disease. We identified citalopram, a selective serotonin reuptake inhibitor, in a small molecule screen of FDA-approved drugs that rescued neuronal dysfunction and reduced aggregation using a Caenorhabditis elegans model of mutant ataxin 3-induced neurotoxicity. MOD-5, the C. elegans orthologue of the serotonin transporter and cellular target of citalopram, and the serotonin receptors SER-1 and SER-4 were strong genetic modifiers of ataxin 3 neurotoxicity and necessary for therapeutic efficacy. Moreover, chronic treatment of CMVMJD135 mice with citalopram significantly reduced ataxin 3 neuronal inclusions and astrogliosis, rescued diminished body weight and strikingly ameliorated motor symptoms. These results suggest that small molecule modulation of serotonergic signalling represents a promising therapeutic target for Machado-Joseph disease. PMID- 26373606 TI - Ethical considerations in functional magnetic resonance imaging research in acutely comatose patients. PMID- 26373605 TI - Cerebrospinal fluid neurogranin: relation to cognition and neurodegeneration in Alzheimer's disease. AB - Synaptic dysfunction is linked to cognitive symptoms in Alzheimer's disease. Thus, measurement of synapse proteins in cerebrospinal fluid may be useful biomarkers to monitor synaptic degeneration. Cerebrospinal fluid levels of the postsynaptic protein neurogranin are increased in Alzheimer's disease, including in the predementia stage of the disease. Here, we tested the performance of cerebrospinal fluid neurogranin to predict cognitive decline and brain injury in the Alzheimer's Disease Neuroimaging Initiative study. An in-house immunoassay was used to analyse neurogranin in cerebrospinal fluid samples from a cohort of patients who at recruitment were diagnosed as having Alzheimer's disease with dementia (n = 95) or mild cognitive impairment (n = 173), as well as in cognitively normal subjects (n = 110). Patients with mild cognitive impairment were grouped into those that remained cognitively stable for at least 2 years (stable mild cognitive impairment) and those who progressed to Alzheimer's disease dementia during follow-up (progressive mild cognitive impairment). Correlations were tested between baseline cerebrospinal fluid neurogranin levels and baseline and longitudinal cognitive impairment, brain atrophy and glucose metabolism within each diagnostic group. Cerebrospinal fluid neurogranin was increased in patients with Alzheimer's disease dementia (P < 0.001), progressive mild cognitive impairment (P < 0.001) and stable mild cognitive impairment (P < 0.05) compared with controls, and in Alzheimer's disease dementia (P < 0.01) and progressive mild cognitive impairment (P < 0.05) compared with stable mild cognitive impairment. In the mild cognitive impairment group, high baseline cerebrospinal fluid neurogranin levels predicted cognitive decline as reflected by decreased Mini-Mental State Examination (P < 0.001) and increased Alzheimer's Disease Assessment Scale-cognitive subscale (P < 0.001) scores at clinical follow up. In addition, high baseline cerebrospinal fluid neurogranin levels in the mild cognitive impairment group correlated with longitudinal reductions in cortical glucose metabolism (P < 0.001) and hippocampal volume (P < 0.001) at clinical follow-up. Furthermore, within the progressive mild cognitive impairment group, elevated cerebrospinal fluid neurogranin levels were associated with accelerated deterioration in Alzheimer's Disease Assessment Scale-cognitive subscale (beta = 0.0017, P = 0.01). These data demonstrate that cerebrospinal fluid neurogranin is increased already at the early clinical stage of Alzheimer's disease and predicts cognitive deterioration and disease-associated changes in metabolic and structural biomarkers over time. PMID- 26373608 TI - Hypothalamic energy metabolism is impaired by doxorubicin independently of inflammation in non-tumour-bearing rats. AB - We sought to explore the effects of doxorubicin on inflammatory profiles and energy metabolism in the hypothalamus of rats. To investigate these effects, we formed two groups: a control (C) group and a Doxorubicin (DOXO) group. Sixteen rats were randomly assigned to either the control (C) or DOXO groups. The hypothalamus was collected. The levels of interleukin (IL)-1beta, IL-6, IL-10, TNF-alpha and energy metabolism (malate dehydrogenase, complex I and III activities) were analysed in the hypothalamus. The DOXO group exhibited a decreased body weight (p < 0.01). Hypothalamic malate dehydrogenase activity was reduced when compared with control (p < 0.05). In addition, pro-inflammatory cytokine levels were unchanged. Therefore, our results demonstrate that doxorubicin leads to an impairment of ?hypothalamic energy metabolism, but do not affect the inflammatory pathway. SIGNIFICANCE PARAGRAPH: The hypothalamus is a central organ that regulates a great number of functions, such as food intake, temperature and energy expenditure, among others. Doxorubicin can lead to deep anorexia and metabolic chaos; thus, we observed the effect of this chemotherapeutic drug on the inflammation and metabolism in rats after the administration of doxorubicin in order to understand the central effect in the hypothalamus. Drug treatment by doxorubicin is used as a cancer therapy; however the use of this drug may cause harmful alterations to the metabolism. Thus, further investigations are needed on the impact of drug therapy over the long term. PMID- 26373609 TI - Self-assembled copper(II) metallacycles derived from asymmetric Schiff base ligands: efficient hosts for ADP/ATP in phosphate buffer. AB - Novel asymmetric Schiff base ligands 2-{[3-(3-hydroxy-1-methyl-but-2 enylideneamino)-2,4,6-trimethylphenylimino]-methyl}-phenol (H2L(1)) and 1-{[3-(3 hydroxy-1-methyl-but-2-enylideneamino)-2,4,6-trimethylphenylimino]-methyl} naphthalen-2-ol (H2L(2)) possessing dissimilar N,O-chelating sites and copper(ii) metallacycles (CuL(1))4 (1) and (CuL(2))4 (2) based on these ligands have been described. The ligands and complexes have been thoroughly characterized by satisfactory elemental analyses, and spectral (IR, (1)H, (13)C NMR, ESI-MS, UV/vis) and electrochemical studies. Structures of H2L(2) and 1 have been unambiguously determined by X-ray single crystal analyses. The crystal structure of H2L(2) revealed the presence of two distinct N,O-chelating sites on dissimilar cores (naphthalene and beta-ketoaminato groups) offering a diverse coordination environment. Metallacycles 1 and 2 having a cavity created by four Cu(ii) centres coordinated in a homo- and heteroleptic fashion with respective ligands act as efficient hosts for adenosine-5'-diphosphate (ADP) and adenosine-5'-triphosphate (ATP) respectively, over other nucleoside polyphosphates (NPPs). The disparate sensitivity of these metallacycles toward ADP and ATP has been attributed to the size of the ligands assuming diverse dimensions and spatial orientations. These are attuned for pi-pi stacking and electrostatic interactions suitable for different guest molecules under analogous conditions, metallacycle 1 offers better orientation for ADP, while 2 for ATP. The mechanism of the host-guest interaction has been investigated by spectral and electrochemical studies and supported by molecular docking studies. PMID- 26373611 TI - Micelle PCR reduces chimera formation in 16S rRNA profiling of complex microbial DNA mixtures. AB - 16S rRNA gene profiling has revolutionized the field of microbial ecology. Many researchers in various fields have embraced this technology to investigate bacterial compositions of samples derived from many different ecosystems. However, it is important to acknowledge the current limitations and drawbacks of 16S rRNA gene profiling. Although sample handling, DNA extraction methods and the choice of universal 16S rRNA gene PCR primers are well known factors that could seriously affect the final results of microbiota profiling studies, inevitable amplification artifacts, such as chimera formation and PCR competition, are seldom appreciated. Here we report on a novel micelle based amplification strategy, which overcomes these limitations via the clonal amplification of targeted DNA molecules. Our results show that micelle PCR drastically reduces chimera formation by a factor of 38 (1.5% vs. 56.9%) compared with traditional PCR, resulting in improved microbial diversity estimates. In addition, compartmentalization during micelle PCR prevents PCR competition due to unequal amplification rates of different 16S template molecules, generating robust and accurate 16S microbiota profiles required for comparative studies (e.g. longitudinal surveys). PMID- 26373613 TI - Abstracts from the 9th International Conference on Equine Exercise Physiology, 15 20 June, 2014 Chester, UK. PMID- 26373612 TI - Shape-controlled synthesis and influence of W doping and oxygen nonstoichiometry on the phase transition of VO2. AB - Monoclinic VO2(M) in nanostructure is a prototype material for interpreting correlation effects in solids with fully reversible phase transition and for the advanced applications to smart devices. Here, we report a facile one-step hydrothermal method for the controlled growth of single crystalline VO2(M/R) nanorods. Through tuning the hydrothermal temperature, duration of the hydrothermal time and W-doped level, single crystalline VO2(M/R) nanorods with controlled aspect ratio can be synthesized in large quantities, and the crucial parameter for the shape-controlled synthesis is the W-doped content. The dopant greatly promotes the preferential growth of (110) to form pure phase VO2(R) nanorods with high aspect ratio for the W-doped level = 2.0 at% sample. The shape controlled process of VO2(M/R) nanorods upon W-doping are systematically studied. Moreover, the phase transition temperature (Tc) of VO2 depending on oxygen nonstoichiometry is investigated in detail. PMID- 26373616 TI - Bloch-like waves in random-walk potentials based on supersymmetry. AB - Bloch's theorem was a major milestone that established the principle of bandgaps in crystals. Although it was once believed that bandgaps could form only under conditions of periodicity and long-range correlations for Bloch's theorem, this restriction was disproven by the discoveries of amorphous media and quasicrystals. While network and liquid models have been suggested for the interpretation of Bloch-like waves in disordered media, these approaches based on searching for random networks with bandgaps have failed in the deterministic creation of bandgaps. Here we reveal a deterministic pathway to bandgaps in random-walk potentials by applying the notion of supersymmetry to the wave equation. Inspired by isospectrality, we follow a methodology in contrast to previous methods: we transform order into disorder while preserving bandgaps. Our approach enables the formation of bandgaps in extremely disordered potentials analogous to Brownian motion, and also allows the tuning of correlations while maintaining identical bandgaps, thereby creating a family of potentials with 'Bloch-like eigenstates'. PMID- 26373614 TI - Body composition, maximal aerobic performance and inflammatory biomarkers in endurance-trained athletes. AB - This study was designed to examine the relationships between body composition, cardiorespiratory fitness and simultaneously measured inflammatory parameters in endurance-trained athletes. In 20 well-trained rowers (19.0 +/- 2.9 years; 185.6 +/- 4.8 cm; 85.7 +/- 10.8 kg; 17.1 +/- 5.1% body fat; maximal oxygen consumption [VO2 max]: 63.9 +/- 8.5 ml min-1 kg-1 ), body composition was measured by dual energy X-ray absorptiometry and cardiorespiratory fitness by direct VO2 max test. Twelve inflammatory factors [interleukin (IL)-2, IL-4, IL-6, IL-8, IL-10, vascular endothelial growth factor, interferon-gamma (IFN-gamma), tumour necrosis factor-alpha, IL-1alpha, IL-1beta, monocyte chemoattractant protein-1 (MCP-1), epidermal growth factor (EGF)] were analysed from serum samples. Serum IFN-gamma was related (P<0.05) to fat-free mass (FFM) (r = -0.56) and muscle mass (r = 0.50). The stepwise regression analysis showed that IFN-gamma explained 27.5%, and IFN-gamma and IL-6 together explained 39.8% of the variability of FFM, while IFN-gamma explained 21.1%, and IFN-gamma together with EGF explained 36.6% of the variability of muscle mass in male rowers. Serum IL-8 (r = -0.65) and VEGF (r = 0.48) correlated (P<0.05) with VO2 max kg-1 . Serum IL-8 explained 38.5% of the variability of VO2 max kg-1 . Significant correlations were also found among several inflammatory parameters, indicating that various inflammatory cytokines act on the body as an ensemble. In conclusion, this cross-sectional study in endurance-trained male rowers showed that FFM and muscle mass were negatively correlated with serum IFN-gamma level, whereas cardiorespiratory fitness was negatively related to serum IL-8 level. PMID- 26373617 TI - CD146 attenuation in cancer-associated fibroblasts promotes pancreatic cancer progression. AB - Cancer-associated fibroblasts (CAFs) are heterogeneous cell populations that influence tumor initiation and progression. CD146 is a cell membrane protein whose expression has been implicated in multiple human cancers. CD146 expression is also detected in pancreatic cancer stroma; however, the role it plays in this context remains unclear. This study aimed to clarify the function and significance of CD146 expression in pancreatic cancer. We performed immunohistochemical staining to investigate the prevalence of CD146 expression in stromal fibroblasts in pancreatic cancer. We also examined the influence of CD146 on CAF-mediated tumor invasion and migration and CAF activation using CD146 small interfering RNA or overexpression plasmids in primary cultures of CAFs derived from pancreatic cancer tissues. CD146 expression in CAFs was associated with high grade pancreatic intraepithelial neoplasia and low histological grade invasive ductal carcinoma of the pancreas, while patients with low CD146 expression had a poorer prognosis. Blocking CD146 expression in CAFs significantly enhanced tumor cell migration and invasion in a co-culture system. CD146 knockdown also promoted CAF activation, possibly by inducing the production of pro-tumorigenic factors through modulation of NF-kappaB activity. Consistently, overexpression of CD146 in CAFs inhibited migration and invasion of co-cultured cancer cells. Finally, CD146 expression in CAFs was reduced by interaction with cancer cells. Our findings suggest that decreased CD146 expression in CAFs promotes pancreatic cancer progression. (c) 2015 Wiley Periodicals, Inc. PMID- 26373618 TI - Morphology and molecular analysis of Mizelleus indicus Jain () and M. longicirrus (Tripathi, ) Venkatanarasaiah & Kulkarni 1981 (Monogenea, Dactylogyridae) from the freshwater shark Wallago attu in the Ganga River, India. AB - Species of the genus Mizelleus Jain (1957) have always been controversial regarding identification and validity. Members of this group of species differ from each other in the morphology of their hard parts, which can be misleading and subject to differing interpretation among scientists. Therefore, the main objective of present study was to identify Mizelleus worms by morphological methods and molecular analysis on the basis of 18S ribosomal DNA to clarify their phylogenetic status. In this study, specimens were isolated from the gill filaments of Wallago attu (Siluriformes) and studied morphologically. In accordance with morphological characters, the specimens were found to be Mizelleus indicus and Mizelleus longicirrus. Partial sequences of nuclear 18S rDNA of these two species were amplified. The results confirm the phylogenetic relationships and taxonomic validation of M. indicus and M. longicirrus in India. PMID- 26373619 TI - S159P mutation of keratin 10 gene causes severe form of epidermolytic hyperkeratosis. PMID- 26373620 TI - Isotactic rac-Lactide Polymerization with Copper Complexes: The Influence of Complex Nuclearity. AB - Diiminopyrrolide copper alkoxide complexes, LCuOR (OR(1)=N,N-dimethylamino ethoxide, OR(2)=2-pyridyl methoxide), are active for the polymerization of rac lactide at ambient temperature in benzene to yield polymers with M(w)/M(n)=1.0 1.2. X-ray diffraction studies showed bridged dinuclear complexes in the solid state for both complexes. While LCuOR(1) provided only atactic polylactide, LCuOR(2) produced partially isotactic polylactide (P(m)=0.7). The difference in stereocontrol is attributed to a dinuclear active species for LCuOR(2) in contrast to a mononuclear species for LCuOR(1). PMID- 26373621 TI - Erratum: G Protein-coupled Estrogen Receptor Protects from Atherosclerosis. PMID- 26373624 TI - Abstracts from the International Surgical Congress of the Association of Surgeons of Great Britain and Ireland, Manchester, UK, 22-24 April 2015. PMID- 26373625 TI - Molecularly imprinted polymers coupled to matrix assisted laser desorption ionization mass spectrometry for femtomoles detection of cardiac troponin I peptides. AB - Molecularly imprinted polymers (MIPs) were combined to MALDI-TOF-MS to evaluate a selective enrichment (SE) method for the determination of clinically relevant biomarkers from complex biological samples. The concept was proven with the myocardial injury marker Troponin I (cTnI). In a first part, MIP materials entailed for the recognition of cTnI epitopes (three peptides selected) were prepared and characterized in dimensions (0.7-2MUm), dissociation constants (58 817 nM), kinetics of binding (5-60 min), binding capacity (ca. 1.5 ug/mg polymer), imprinting factors (3 > IF > 5) and selectivity for the peptide epitope. Then, the MIPs, incubated with cTnI peptides and spotted on the target with the DHB matrix, were assayed for the desorption of the peptides in MALDI-TOF MS. The measured detection limit was ca. 300 femtomols. Finally, the MIP-SE MALDI TOF-MS was tested for its ability to enrich in the cTnI peptides from a complex sample, mimic of serum (i.e. 81 peptides of digested albumin). The MIP-SE MALDI TOF-MS successfully enriched in cTnI peptides from the complex sample proving the technique could offer a flexible platform to prepare entailed materials suitable for diagnostic purposes. PMID- 26373626 TI - Leptospirosis infection in a homeless patient in December in Tokyo: a case report. AB - INTRODUCTION: We report a case of severe leptospirosis that occurred during winter in Tokyo, the capital of Japan. Leptospirosis is endemic in tropical regions and extremely rare in the urban areas of Japan. Only six new cases were reported in Tokyo in 2014. Most leptospirosis cases reported in urban areas of Japan were a result of occupational hazards, and there is no previous report of leptospirosis in a homeless patient in Tokyo. We believe this report could provide a widened perspective about the clinical presentation and epidemiology of leptospirosis in Japan. CASE PRESENTATION: Our patient was a 73-year-old Asian man. He had been homeless for over 10 years, with exposure to rodents and their excrement in parks and on the streets. He presented with fever and severe inflammatory response, satisfying the diagnostic criteria for systemic inflammatory response syndrome. Laboratory findings showed multiple-organ dysfunction, including renal failure, liver failure with increased total bilirubin level, and coagulopathy with decreased platelets. We suspected leptospirosis on the basis of these clinical findings. The diagnosis was also confirmed by polymerase chain reaction first, and paired antibody titers on day 9, in the recovery period, showed positive results for three species. CONCLUSIONS: Our patient's case suggests that even patients without a history of traveling abroad or exposure to freshwater can develop leptospirosis in winter in urban areas in Japan. If a patient has symptoms like fever, calf pain and MOF; as a differential diagnosis we should rule outthe Leptospirosis. From the perspective of sensitivity, specificity, and clinical convenience, polymerase chain reaction could be the preferred diagnostic tool of choice. PMID- 26373627 TI - Longitudinal Change in Performance on the Montreal Cognitive Assessment in Older Adults. AB - OBJECTIVE: The Montreal Cognitive Assessment (MoCA) is a brief screening measure commonly used to determine cognitive status among older adults. Despite the popularity of the MoCA, there has been little research into how performance on the MoCA changes over time in healthy older adults. METHODS: The present study examined a sample of older adults (n = 53) recruited for a longitudinal study of healthy aging. Change in total MoCA score at three time points (baseline, 12 months, and 48 months) and scores from the Repeatable Battery for the Assessment of Neuropsychological Status at five time points (RBANS; baseline 12 months, 24 months, 36 months, and 48 months) were assessed using repeated measures analyses. RESULTS: Total MoCA score significantly increased across time, particularly between the first and second administrations. Scores did not significantly differ between the second (12 month) and third (48 month) administrations. When grouped by baseline performance, individuals who scored low at baseline significantly improved performance at 12-month testing, but had little change between 12- and 48-month testing. Conversely, individuals who scored high at baseline did not significantly change between baseline and 12-month testing, but improved between 12- and 48-month testing. RBANS scores did not significantly change over time. CONCLUSIONS: These results suggest that the MoCA may be susceptible to practice effects, particularly between the first and second administrations. These practice effects should be taken into consideration when repeatedly employing the MoCA to screen for cognitive status in healthy older adults. PMID- 26373628 TI - Neurogenic orthostatic hypotension: roles of norepinephrine deficiency in its causes, its treatment, and future research directions. AB - BACKGROUND: Although a diversity of neurotransmitters and hormones participate in controlling blood pressure, norepinephrine released from postganglionic sympathetic nerve terminals is an important mediator of the rapid regulation of cardiovascular function required for homeostasis of cerebral perfusion. Hence, neurogenic orthostatic hypotension (NOH) often represents a deficiency of noradrenergic responsiveness to postural change. RESEARCH DESIGN AND METHODS: PubMed searches with 'orthostatic hypotension' and 'norepinephrine' as conjoint search terms and no restriction on language or date, so as to survey the pathophysiologic and clinical relevance of norepinephrine deficiency for current NOH interventions and for future directions in treatment and research. RESULTS: Norepinephrine deficiency in NOH can arise peripherally, due to cardiovascular sympathetic denervation (as in pure autonomic failure, Parkinson's disease, and a variety of neuropathies), or centrally, due to a failure of viscerosensory signals to generate adequate sympathetic traffic to intact sympathetic nerve endings (as in multiple system atrophy). Nonpharmacologic countermeasures such as pre-emptive water intake may yield blood-pressure increases exceeding those achieved pharmacologically. For patients with symptomatic NOH unresponsive to such strategies, a variety of pharmacologic interventions have been administered off-label on the basis of drug mechanisms expected to increase blood pressure via blood-volume expansion or vasoconstriction. Two pressor agents have received FDA approval: the sympathomimetic midodrine and more recently the norepinephrine prodrug droxidopa. CONCLUSIONS: Pressor agents are important for treating symptomatic NOH in patients unresponsive to lifestyle changes alone. However, the dysautonomia underlying NOH often permits blood-pressure excursions toward both hypotension and hypertension. Future research should aim to shed light on the resulting management issues, and should also explore the possibility of pharmacotherapy selectively targeting orthostatic blood-pressure decreases. PMID- 26373629 TI - Achievement of treatment goals with canagliflozin in patients with type 2 diabetes mellitus: a pooled analysis of randomized controlled trials. AB - OBJECTIVE: To evaluate attainment of diabetes-related treatment goals with canagliflozin, a sodium glucose co-transporter 2 inhibitor, versus placebo in patients with type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS: Data were pooled from four 26-week, placebo-controlled, Phase 3 studies of patients with T2DM (N = 2313). Goal attainment with canagliflozin 100 and 300 mg versus placebo was evaluated in the overall population, and in subgroups based on age and sex, at baseline and Week 26. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT01081834, NCT01106677, NCT01106625, NCT01106690. MAIN OUTCOME MEASURES: Proportion of patients achieving hemoglobin A1C (A1C) < 7.0% and <= 6.5%, systolic blood pressure (SBP) < 140 and < 130 mmHg, diastolic blood pressure (DBP) < 90 and < 80 mmHg, low-density lipoprotein cholesterol (LDL-C) < 100 mg/dL (2.6 mmol/L), high-density lipoprotein cholesterol (HDL-C) >= 40 mg/dL (1.0 mmol/L), and the composite endpoint of A1C < 7.0%, BP < 130/80 mmHg, and LDL-C <100 mg/dL (2.6 mmol/L) at baseline and Week 26, and proportion with body weight reduction >= 5% at Week 26. RESULTS: At baseline, similar proportions of patients met diabetes-related treatment goals across groups. At Week 26, a greater proportion of patients achieved A1C, SBP, DBP, and HDL-C goals with canagliflozin 100 and 300 mg compared with placebo. More patients achieved body weight reduction of >= 5% with canagliflozin 100 and 300 mg versus placebo at Week 26. Fewer patients had LDL-C < 100 mg/dL (2.6 mmol/L) at Week 26 with canagliflozin 100 and 300 mg versus placebo. Canagliflozin 100 and 300 mg also provided better attainment of the composite endpoint of A1C <7.0%, BP < 130/80 mmHg, and LDL-C < 100 mg/dL (2.6 mmol/L) compared with placebo. Attainment of diabetes-related treatment goals was generally similar regardless of age and sex. Key limitations of this analysis include the selection of specific treatment targets that may not be reflective of all patient experiences, the non-prespecified, post hoc nature of the analysis, and the short duration of studies included in the pooled population. CONCLUSION: Canagliflozin was associated with better attainment of diabetes-related treatment goals compared with placebo, and was generally well tolerated at 26 weeks. PMID- 26373632 TI - Development and examination of the psychometric properties of the Learning Experience Scale in nursing. AB - This paper examines the psychometric properties of the Learning Experience Scale. A survey method was used to collect data from a total of 502 nurses. Data were analyzed by factor analysis and the known-groups technique to examine the construct validity of the scale. In addition, internal consistency was evaluated by Cronbach's alpha, and stability was examined by test-retest correlation. Factor analysis showed that the Learning Experience Scale consisted of five factors: learning from practice, others, training, feedback, and reflection. The scale also had the power to discriminate between nurses with high and low levels of nursing competence. The internal consistency and the stability of the scale were also acceptable. The Learning Experience Scale is a valid and reliable instrument, and helps organizations to effectively design learning interventions for nurses. PMID- 26373631 TI - Plasma soluble Tim-3 emerges as an inhibitor in sepsis: sepsis contrary to membrane Tim-3 on monocytes. AB - Immune dysfunction is the main characteristic of sepsis. T cell Ig and mucin domain protein 3 (Tim-3) on the monocytes has been reported to promote immune homeostasis during sepsis, but the influences of plasm soluble Tim-3 (sTim-3) on the immune system during sepsis remain unknown. Here, 100 patients with different severities of sepsis (40 sepsis, 42 severe sepsis, and 18 septic shock) were enrolled in this study. The Tim-3 and human leukocyte antigen-DR (HLA-DR) on the circulating monocytes were detected using flow cytometry. Plasma sTim-3 was detected by enzyme-linked immunosorbent assay. Inflammatory factors and two kinds of A disintegrin and metalloprotease (ADAM) - ADAM10 and ADAM17 were assessed. The Tim-3 and HLA-DR on the monocytes decreased with increasing sepsis severity. The sTim-3 was reduced in the sepsis and severe sepsis patients but was elevated in the septic shock patients who exhibited significant immunosuppression as predicted by HLA-DR. sTim-3 levels were negatively correlated with IL-12 and TNF alpha. ADAM10 and ADAM17, sheddases of Tim-3, exhibited trends toward elevations in the septic shock group. In conclusion, sTim-3 was involved in the development of sepsis. The homeostasis-promoting role of the Tim-3 on the monocytes was disrupted, while the inhibitory role of sTim-3 emerged during sepsis-induced immunosuppression. PMID- 26373633 TI - Detection of viable plasmodium ookinetes in the midguts of anopheles coluzzi using PMA-qrtPCR. AB - BACKGROUND: Mosquito infection with malaria parasites depends on complex interactions between the mosquito immune response, the parasite developmental program and the midgut microbiota. Simultaneous monitoring of the parasite and bacterial dynamics is important when studying these interactions. PCR based methods of genomic DNA (gDNA) have been widely used, but their inability to discriminate between live and dead cells compromises their application. The alternative method of quantification of mRNA mainly reports on cell activity rather than density. METHOD: Quantitative real-time (qrt) PCR in combination with Propidium Monoazide (PMA) treatment (PMA-qrtPCR) has been previously used for selectively enumerating viable microbial cells. PMA penetrates damaged cell membranes and intercalates in the DNA inhibiting its PCR amplification. Here, we tested the potential of PMA-qrtPCR to discriminate between and quantify live and dead Plasmodium berghei malarial parasites and commensal bacteria in the midgut of Anopheles coluzzii Coetzee & Wilkerson 2013 (formerly An. gambiae M-form). RESULTS: By combining microscopic observations with reverse transcriptase PCR (RT PCR) we reveal that, in addition to gDNA, mRNA from dead parasites also persists inside the mosquito midgut, therefore its quantification cannot accurately reflect live-only parasites at the time of monitoring. In contrast, pre-treating the samples with PMA selectively inhibited qrtPCR amplification of parasite gDNA, with about 15 cycles (Ct-value) difference between PMA-treated and control samples. The limit of detection corresponds to 10 Plasmodium ookinetes. Finally, we show that the PMA-qrtPCR method can be used to quantify bacteria that are present in the mosquito midgut. CONCLUSION: The PMA-qrtPCR is a suitable method for quantification of viable parasites and bacteria in the midgut of Anopheles mosquitoes. The method will be valuable when studying the molecular interactions between the mosquito, the malaria parasite and midgut microbiota. PMID- 26373635 TI - A literature review of antimicrobial resistance in Pathogens associated with bovine respiratory disease. AB - The objective of this paper was to perform a critical review of the literature as it pertains to the current status of antimicrobial resistance in pathogens associated with bovine respiratory disease (BRD) in beef cattle and to provide a concise yet informative narrative on the most relevant publications available. As such, the scientific literature contained in PubMed, AGRICOLA, and CAB were searched in February of 2014 for articles related to susceptibility testing of Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni from cases of BRD. Titles and abstracts were read and 105 articles that were relevant to the subject of BRD antibiotic resistance were attained for further review. After the application of exclusion criterion (publications must have originated from North America, be in English, adhere to standards set forth by the Clinical and Laboratory Standards Institute, and be concerning antimicrobial resistance in BRD in beef cattle), 16 articles remained and are the focus of this publication. Due to the disparate data from the few studies that investigate susceptibility testing of BRD pathogens, a quantitative assessment or meta-analysis was not performed on the studies presented in this review. However, considering diagnostic lab data, there appears to be a clear trend of a decrease in susceptibility of the three major BRD pathogens to the antimicrobials used commonly for treatment and control of BRD. Studies performing sensitivity testing on healthy cattle report much lower resistance, but it remains unclear if this is because of a true lack of resistance mechanisms, or if the isolates do contain quiescent genes for resistance that are only phenotypically expressed following the administration of an antimicrobial for either treatment or control of BRD. Future research to address this question of genotype and phenotypic expression before and after antimicrobial administration will further advance our knowledge in this area. PMID- 26373636 TI - Antibody based immunotherapy for multiple myeloma: it's about time. AB - Monoclonal antibodies have made an indelible impact on cancer practice. Historically multiple myeloma (MM) has lagged behind in benefitting from this treatment modality. Recent years have seen a tremendous increase in the number of therapeutic antibodies being developed for treatment of MM. Unconjugated anti-CD 38 antibody Daratumumab and the anti-SLAMF7 antibody elotuzumab are in advanced stages of development and are expected to have a major impact in the management of MM. The immunotoxin Indatuximab Ravtansine is in early stages of development and the results appear encouraging. The role of monoclonal antibodies in myeloma will continue to evolve and, like other lymphoid malignancies, they are likely to have the greatest impact when combined with other anti-myeloma agents. PMID- 26373634 TI - Mindfulness based cognitive therapy versus treatment as usual in adults with attention deficit hyperactivity disorder (ADHD). AB - BACKGROUND: Adults with attention deficit hyperactivity disorder (ADHD) often present with a lifelong pattern of core symptoms that is associated with impairments of functioning in daily life. This has a substantial personal and economic impact. In clinical practice there is a high need for additional or alternative interventions for existing treatments, usually consisting of pharmacotherapy and/or psycho-education. Although previous studies show preliminary evidence for the effectiveness of mindfulness-based interventions in reducing ADHD symptoms and improving executive functioning, these studies have methodological limitations. This study will take account of these limitations and will examine the effectiveness of Mindfulness Based Cognitive Therapy (MBCT) in further detail. METHODS/DESIGN: A multi-centre, parallel-group, randomised controlled trial will be conducted in N = 120 adults with ADHD. Patients will be randomised to MBCT in addition to treatment as usual (TAU) or TAU alone. Assessments will take place at baseline and at three, six and nine months after baseline. Primary outcome measure will be severity of ADHD symptoms rated by a blinded clinician. Secondary outcome measures will be self-reported ADHD symptoms, executive functioning, mindfulness skills, self-compassion, positive mental health and general functioning. In addition, a cost-effectiveness analysis will be conducted. DISCUSSION: This trial will offer valuable information about the clinical and cost-effectiveness of MBCT in addition to TAU compared to TAU alone in adults swith ADHD. TRIAL REGISTRATION: ClinicalTrials.gov NCT02463396. Registered 8 June 2015. PMID- 26373637 TI - Analyzing barriers and facilitators to the implementation of an action plan to strengthen the midwifery professional role: a Moroccan case study. AB - BACKGROUND: As part of a national strategy for reaching Millennium Development Goals 4 and 5 in Morocco, an action plan covering three systems (sociocultural, educational and professional) was developed to strengthen midwives' professional role in order to contribute to high quality maternity care. This study aimed to understand the implementation process by identifying the characteristics of this intervention and the dimensions of the three-systems which could act as barriers to/facilitators of the implementation process. We used a conceptual framework that builds on Hatem-Asmar's model that describes change in a health professional role; and on the Consolidated Framework for Implementation Research for our analysis. METHODS: An embedded case study with three levels of analysis was conducted during June and July 2010. Data were collected through 11 semi structured interviews, 20 focus groups, training session observations and documents. A purposive sample of 106 multi-stakeholders from two Moroccan regions (health professionals, academic staff, students, medical administrative officers and health programmers) and one international consultant were recruited. A thematic analysis was conducted using QDA Miner. RESULTS: Data showed a failure to carry out the plan as intended. Seventeen barriers and seven facilitators were identified. Misalignment of the values, methods, actors and targets of the sociocultural system with the values, methods and actors of the educational and professional systems, on one hand, and with the intervention, on the other hand, were likely the greatest impediments to implementing the plan. The bureaucratic structure and lack of readiness of the sociocultural system were among the most influential barriers to: dissemination of information, involvement of key actors in the process and readiness of the educational system. The main facilitators were the values promoted related to human rights, and the national and international policies to strengthen midwifery and reduce maternal mortality. The plan was perceived as beneficial, but complex and externally driven. CONCLUSIONS: The findings suggest that successful implementation requires redesigning the implementation strategy to adapt to the factors identified in our study. The results would be very useful to health planners seeking the expansion of such an intervention to other developing countries looking to strengthen midwives' role and to improve maternity health care services. PMID- 26373640 TI - Comparison of Performance of Docking, LIE, Metadynamics and QSAR in Predicting Binding Affinity of Benzenesulfonamides. AB - The design of inhibitors specific for one relevant carbonic anhydrase isozyme is the major challenge in the new therapeutic agents development. Comparative computational chemical structure and biological activity relationship studies on a series of carbonic anhydrase II inhibitors, benzenesulfonamide derivatives, bearing pyrimidine moieties are reported in this paper using docking, Linear Interaction Energy (LIE), Metadynamics and Quantitative Structure Activity Relationship (QSAR) methods. The computed binding affinities were compared with the experimental data with the goal to explore strengths and weaknesses of various approaches applied to the investigated carbonic anhydrase/inhibitor system. From the tested methods initially only QSAR showed promising results (R2=0.83-0.89 between experimentally determined versus predicted pKd values.). Possible reasons for this performance were discussed. A modification of the LIE method was suggested which used an alternative LIE-like equation yielding significantly improved results (R2 between the experimentally determined versus the predicted DeltaG(bind) improved from 0.24 to 0.50). PMID- 26373638 TI - Estimating the molecular evolutionary rates of mitochondrial genes referring to Quaternary ice age events with inferred population expansions and dispersals in Japanese Apodemus. AB - BACKGROUND: Determining reliable evolutionary rates of molecular markers is essential in illustrating historical episodes with phylogenetic inferences. Although emerging evidence has suggested a high evolutionary rate for intraspecific genetic variation, it is unclear how long such high evolutionary rates persist because a recent calibration point is rarely available. Other than using fossil evidence, it is possible to estimate evolutionary rates by relying on the well-established temporal framework of the Quaternary glacial cycles that would likely have promoted both rapid expansion events and interisland dispersal events. RESULTS: We examined mitochondrial cytochrome b (Cytb) and control region (CR) gene sequences in two Japanese wood mouse species, Apodemus argenteus and A. speciosus, of temperate origin and found signs of rapid expansion in the population from Hokkaido, the northern island of Japan. Assuming that global warming after the last glacial period 7-10 thousand years before present (kyr BP) was associated with the expansion, the evolutionary rates (sites per million years, myr) of Cytb and CR were estimated as 11-16 % and 22-32 %, respectively, for A. argenteus, and 12-17 % and 17-24 %, respectively, for A. speciosus. Additionally, the significant signature of rapid expansion detected in the mtDNA sequences of A. speciosus from the remaining southern main islands, Honshu, Shikoku, and Kyushu, provided an estimated Cytb evolutionary rate of 3.1 %/site/myr under the assumption of a postglacial population expansion event long ago, most probably at 130 kyr BP. Bayesian analyses using the higher evolutionary rate of 11-17 %/site/myr for Cytb supported the recent demographic or divergence events associated with the Last Glacial Maximum. However, the slower evolutionary rate of 3.1 %/site/myr would be reasonable for several divergence events that were associated with glacial periods older than 130 kyr BP. CONCLUSIONS: The faster and slower evolutionary rates of Cytb can account for divergences associated with the last and earlier glacial maxima, respectively, in the phylogenetic inference of murine rodents. The elevated evolutionary rate seemed to decline within 100,000 years. PMID- 26373641 TI - The Piezo Mechanosensitive Ion Channels: May the Force Be with You! AB - Piezo1 and Piezo2 are critically required for nonselective cationic mechanosensitive channels in mammalian cells. Within the last 5 years, tremendous progress has been made in understanding the function of Piezo1/2 in embryonic development, physiology, and associated disease states. A recent breakthrough was the discovery of a chemical opener for Piezo1, indicating that mechanosensitive ion channels can be opened independently of mechanical stress. We will review these new exciting findings, which might pave the road for the identification of novel therapeutic strategies. PMID- 26373642 TI - Dynamic Evaluation of Coronary Anomalies Originating from the Opposite Sinus of Valsalva (ACAOS). AB - OPINION STATEMENT: Coronary anomalies originating from the opposite sinus of Valsalva (ACAOS) are a rare anomaly associated with sudden cardiac death. Dynamic, invasive evaluation using coronary angiography, intravascular ultrasound, and fractional flow reserve can more clearly identify important pathophysiologic variants and guide treatment. This dynamic evaluation can assist the clinician in the appropriate surgical and percutaneous treatment options and aid in patient counseling. Long-term outcomes data regarding treatment and prognosis is still lacking. PMID- 26373643 TI - A cytogenetic study of hospital workers occupationally exposed to radionuclides in Serbia: premature centromere division as novel biomarker of exposure? AB - PURPOSE: The health risk of chronic exposure to radionuclides includes changes in the genome (e.g., chromosomal aberrations and micronuclei) that increase chromosomal instability. There are also other phenomena, which seem to appear more frequently in metaphases of exposed persons (such as premature centromere division). The aim of this study was to discover whether or not there is correlation between incidence of named cytogenetic changes in persons occupationally exposed to radionuclides in comparison with unexposed control group, and if significant correlation is determined, can premature centromere division be consider as a biomarker of radiation exposure? METHODS: The exposed group comprised 50 individuals occupationally exposed to radionuclides. The reference control group consisted of 40 unexposed individuals. Chromosomal aberrations, micronuclei and premature centromere division were analyzed according to a standard International Atomic Energy Agency protocol. Statistical analyses were performed using SPSS 17.0 statistics. RESULTS: The means for analyzed cytogenetic changes were significantly higher in the exposed group. Positive correlation between them was found in exposed group. Premature centromere division parameter PCD5-10 was selected as particularly suitable for separating groups (exposed/unexposed). CONCLUSIONS: Identification of other phenomena related to radionuclide exposure, beside well known, may clarify recent problems in radiobiology concerning the biological response to low doses of ionizing radiation and its consequences. PMID- 26373644 TI - ATR-FTIR Spectroscopy Highlights the Problem of Distinguishing Between Exophiala dermatitidis and E. phaeomuriformis Using MALDI-TOF MS. AB - The present study compared two chemical-based methods, namely, matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS) and attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, to understand the misidentification of Exophiala dermatitidis and Exophiala phaeomuriformis. The study utilized 44 E. dermatitidis and 26 E. phaeomuriformis strains, which were partially treated with strong acids and bases for further evaluation. MALDI-TOF MS and ATR-FTIR spectroscopy data of the two Exophiala species were compared. Data groupings were observed for the chromic acid- and nitric acid-treated species when the black yeast sources were categorized as creosoted-oak sleepers, concrete sleepers, or dishwasher isolates. The MALDI-TOF MS data for the metalloenzyme-containing regions were consistent with the ATR FTIR spectroscopy data. These results indicated that environmental isolates might contain metals not found in human isolates and might interfere with chemical based identification methods. Therefore, MALDI-TOF MS reference libraries should be created for clinical strains and should exclude petroleum-associated environmental isolates. PMID- 26373645 TI - Fructose-Glucose Composite Carbohydrates and Endurance Performance: Critical Review and Future Perspectives. AB - Sports beverages formulated with fructose and glucose composites enhance exogenous carbohydrate oxidation, gut comfort, and endurance performance, relative to single-saccharide formulations. However, a critical review of performance data is absent. We conducted a comprehensive literature review of the effect of fructose:glucose/maltodextrin (glucose or maltodextrin) composites versus glucose/maltodextrin on endurance performance. Mechanistic associations were drawn from effects on carbohydrate metabolism, gut, and other sensory responses. Overall, 14 studies contained estimates of 2.5-3.0-h endurance performance in men, mostly in cycling. Relative to isocaloric glucose/maltodextrin, the ingestion of 0.5-1.0:1-ratio fructose:glucose/maltodextrin beverages at 1.3-2.4 g carbohydrate.min(-1) produced small to moderate enhancements (1-9 %; 95 % confidence interval 0-19) in mean power. When 0.5:1-ratio composites were ingested at >=1.7 g.min(-1), improvements were larger (4-9 %; 2-19) than at 1.4-1.6 g.min(-1) (1-3 %; 0-6). The effect sizes at higher ingestion rates were associated with increased exogenous carbohydrate oxidation rate, unilateral fluid absorption, and lower gastrointestinal distress, relative to control. Solutions containing a 0.7-1.0:1 fructose:glucose ratio were absorbed fastest; when ingested at 1.5-1.8 g.min(-1), a 0.8:1 fructose:glucose ratio conveyed the highest exogenous carbohydrate energy and endurance power compared with lower or higher fructose:glucose ratios. To conclude, ingesting 0.5-1.0:1-ratio fructose:glucose/maltodextrin beverages at 1.3-2.4 g.min(-1) likely benefits 2.5-3.0 h endurance power versus isocaloric single saccharide. Further ratio and dose-response research should determine if meaningful performance benefits of composites accrue with ingestion <1.3 g.min( 1), relative to higher doses. Effects should be established in competition, females, other food formats, and in heat-stress and ultra-endurance exercise where carbohydrate demands may differ from the current analysis. PMID- 26373646 TI - The Effect of Exercise Training on the Energetic Cost of Cycling. AB - BACKGROUND AND OBJECTIVE: The energetic cost of cycling (CE) is a major contributor to cycling performance but whether CE can be improved by exercise intervention remains uncertain. Here, we sought to systematically review and determine the effect of exercise training on CE in healthy humans. METHODS: MEDLINE, Scopus, and Web of Science were searched since their inceptions up until December 2014 for articles assessing the effect of exercise training in healthy subjects on CE, as determined by cycling economy or efficiency. Meta-analyses were performed to determine the standardized mean difference (SMD) in CE between post- and pre-training measurements. Subgroup and meta-regression analyses were used to evaluate potential moderating/confounding factors. RESULTS: Fifty-one studies were included after systematic review, comprising a total of 531 healthy subjects (mean age = 20-66 years). Exercise interventions primarily consisted of endurance and/or strength training ranging from 4 to 34 weeks of duration. After data pooling, the meta-analysis revealed that CE was improved with strength training alone or along with endurance training (n = 16, SMD = -0.50, P < 0.0001) but not with endurance training alone (n = 33, SMD = -0.18, P = 0.08). In further subgroup analyses, endurance training alone was effective in improving CE in previously untrained (n = 20, SMD = -0.21, P = 0.04) but not in trained (n = 6, SMD = 0.09, P = 0.75) subjects. The SMD in CE was associated with the duration of training (n = 51, B = -0.03, P = 0.0002). CONCLUSION: The current meta-analysis provides evidence that CE is improved by exercise training, particularly when strength training or untrained subjects are included. PMID- 26373647 TI - Chest CT examinations in patients presenting with acute chest pain: a pictorial review. AB - Acute chest pain (ACP) is one of the most common presenting symptoms at the emergency department. The differential diagnosis is vast. To exclude life threatening causes, radiologists encounter an increasing amount of thoracic computed tomography (CT) examinations including CT angiography of the heart and great vessels. The dual- and triple-rule CT examinations are currently implemented in clinical practice. We retrospectively identified chest CT examinations in the setting of acute chest pain in our hospitals and collected a variety of common and uncommon cases. In this pictorial essay, we present the most educative cases from patients who presented with acute chest pain in the emergency department of our hospitals and for whom a thoracic CT was ordered. When aortic emergencies, acute coronary syndrome, and pulmonary embolism are excluded, these cases may help the radiologist to suggest alternative diagnoses in the diagnostic challenge of acute chest pain. Teaching Points * The number of chest CT examinations for ACP is increasing.* Chest CT examinations may help suggesting alternative diagnosis in ACP.* Radiologists should be aware of the differential diagnosis of ACP. PMID- 26373648 TI - Inferior vena cava anomalies and variations: imaging and rare clinical findings. AB - PURPOSE: The aim of this paper is to summarize imaging findings of some frequent and infrequent inferior vena cava (IVC) anomalies and variations. CONCLUSIONS: IVC anomalies should be suspected in patients presenting with pulmonary emboli, chronic pain, and deep vein thrombosis. To correctly characterize and classify IVC anomalies and variations is of crucial importance for proper planning of surgical interventions and thus for avoiding serious complications. KEY POINTS: * IVC anomalies should be suspected in patients with pulmonary emboli, pain, and venous thrombosis. * Awareness of IVC anomalies and variations is crucial for clinical and surgical procedures. * Unawareness of these anomalies may lead to severe and deadly complications. PMID- 26373649 TI - Sonographic images of hepato-pancreatico-biliary and intestinal ascariasis: A pictorial review. AB - Despite advancement in the diagnosis and treatment of intestinal helminthiasis, ascariasis remains the most common cause of helminthic infections in the developing countries. Ultrasound offers a rapid, safe, and noninvasive approach to the diagnosis of intestinal ascariasis. Ultrasound is also the modality of choice for diagnosis of hepatobiliary ascariasis, which is relatively rare and is due to migration of intestinal worms through the papilla of Vater. We present an imaging spectrum of hepato-pancreatico-biliary and intestinal ascariasis. MAIN MESSAGES: * Ascariasis refer to infestation by the round worm ascaris lumbricoides. * Ascaris eggs are excreted in faeces and are infective to humans. * Eggs hatch to larva, travel to the lungs and mature to adult worms. * Intestinal obstruction can be caused by multiple ascariasis forming bag of worms. PMID- 26373650 TI - Sexually Explicit Internet Material and Adolescents' Sexual Uncertainty: The Role of Disposition-Content Congruency. AB - Previous research has suggested that adolescents' exposure to sexually explicit internet material (SEIM) may result in sexual uncertainty because the content of SEIM may conflict with what adolescents have learned about sex. However, research on which type of adolescent is most susceptible to the relation between SEIM use and sexual uncertainty is lacking. This study therefore investigated whether the relationship between SEIM use and sexual uncertainty depends on within-gender differences in sexual dispositions (i.e., impersonal sex orientation and hypergendered orientation). Using data from a representative two-wave panel survey among 1765 Dutch adolescents (aged 13-17), I found that SEIM use predicted sexual uncertainty only among girls with a low hypergendered orientation and girls with a relatively high impersonal sex orientation. PMID- 26373651 TI - Thermoregulation in the lizard Psammodromus algirus along a 2200-m elevational gradient in Sierra Nevada (Spain). AB - Achieving optimal body temperature maximizes animal fitness. Since ambient temperature may limit ectotherm thermal performance, it can be constrained in too cold or hot environments. In this sense, elevational gradients encompass contrasting thermal environments. In thermally pauperized elevations, ectotherms may either show adaptations or suboptimal body temperatures. Also, reproductive condition may affect thermal needs. Herein, we examined different thermal ecology and physiology capabilities of the lizard Psammodromus algirus along a 2200-m elevational gradient. We measured field (T(b)) and laboratory-preferred (T(pref)) body temperatures of lizards with different reproductive conditions, as well as ambient (T(a)) and copper-model operative temperature (T(e)), which we used to determine thermal quality of the habitat (d(e)), accuracy (d(b)), and effectiveness of thermoregulation (de-db) indexes. We detected no Tb trend in elevation, while T(a) constrained T(b) only at high elevations. Moreover, while Ta decreased more than 7 degrees C with elevation, T(pref) dropped only 0.6 degrees C, although significantly. Notably, low-elevation lizards faced excess temperature (T(e) > T(pref)). Notably, de was best at middle elevations, followed by high elevations, and poorest at low elevations. Nonetheless, regarding microhabitat, high-elevation de was more suitable in sun-exposed microhabitats, which may increase exposition to predators, and at midday, which may limit daily activity. As for gender, d(b) and d(e)-d(b) were better in females than in males. In conclusion, P. algirus seems capable to face a wide thermal range, which probably contributes to its extensive corology and makes it adaptable to climate changes. PMID- 26373652 TI - Erratum to: Pathogenesis of intracranial aneurysm is mediated by proinflammatory cytokine TNFA and IFNG and through stochastic regulation of IL10 and TGFB1 by comorbid factors. PMID- 26373653 TI - CaMV-35S promoter sequence-specific DNA methylation in lettuce. AB - KEY MESSAGE: We found 35S promoter sequence-specific DNA methylation in lettuce. Additionally, transgenic lettuce plants having a modified 35S promoter lost methylation, suggesting the modified sequence is subjected to the methylation machinery. We previously reported that cauliflower mosaic virus 35S promoter specific DNA methylation in transgenic gentian (Gentiana triflora * G. scabra) plants occurs irrespective of the copy number and the genomic location of T-DNA, and causes strong gene silencing. To confirm whether 35S-specific methylation can occur in other plant species, transgenic lettuce (Lactuca sativa L.) plants with a single copy of the 35S promoter-driven sGFP gene were produced and analyzed. Among 10 lines of transgenic plants, 3, 4, and 3 lines showed strong, weak, and no expression of sGFP mRNA, respectively. Bisulfite genomic sequencing of the 35S promoter region showed hypermethylation at CpG and CpWpG (where W is A or T) sites in 9 of 10 lines. Gentian-type de novo methylation pattern, consisting of methylated cytosines at CpHpH (where H is A, C, or T) sites, was also observed in the transgenic lettuce lines, suggesting that lettuce and gentian share similar methylation machinery. Four of five transgenic lettuce lines having a single copy of a modified 35S promoter, which was modified in the proposed core target of de novo methylation in gentian, exhibited 35S hypomethylation, indicating that the modified sequence may be the target of the 35S-specific methylation machinery. PMID- 26373654 TI - Transcriptomic profiling revealed the regulatory mechanism of Arabidopsis seedlings response to oxidative stress from cryopreservation. AB - KEY MESSAGE: Elevated antioxidant status and positive abiotic stress response in dehydration enhance cell resistance to cryoinjury, and controlling oxidative damage via reactive oxygen species homeostasis maintenance leads to high survival. Cryoprotectants are important for cell survival in cryopreservation, but high concentrations can also cause oxidative stress. Adding vitamin C to the cryoprotectant doubled the survival ratio in Arabidopsis thaliana 60-h seedlings (seedlings after 60-h germination) cryopreservation. In this study, the metabolites and transcriptional profiling of 60-h seedlings were analyzed in both the control cryopreservation procedure (CCP) and an improved cryopreservation procedure (ICP) to reveal the mechanism of plant cell response to oxidative stress from cryopreservation. Reactive oxygen species (ROS) and peroxidation levels reached a peak after rapid cooling-warming in CCP, which were higher than that in ICP. In addition, gene regulation was significantly increased in CCP and decreased in ICP during rapid cooling-warming. Before cryogenic treatment, the number of specifically regulated genes was nearly 10 times higher in ICP dehydration than CCP dehydration. Among these genes, DREBs/CBFs were beneficial to cope with cryoinjury, and calcium-binding protein, OXI1, WRKY and MYB family members as key factors in ROS signal transduction activated the ROS-producing and ROS-scavenging networks including AsA-GSH and GPX cycles involved in scavenging H2O2. Finally, elevated antioxidant status and oxidative stress response in the improved dehydration enhanced seedling resistance to cryogenic treatment, maintained ROS homeostasis and improved cell recovery after cryopreservation. PMID- 26373655 TI - Prevalence of brain and spinal cord inclusions, including dipeptide repeat proteins, in patients with the C9ORF72 hexanucleotide repeat expansion: a systematic neuropathological review. AB - AIM: The current literature shows no consensus on the localization and number of characteristic neuronal inclusions [p62 and dipeptide repeat proteins (DRPs) positive, TDP-43-negative and TDP-43 positive] in the brain and spinal cord of patients with the hexanucleotide repeat expansion on chromosome 9 (C9ORF72 positive patients). This may be due to small sample sizes. A valid brain map of the inclusions in C9ORF72-positive patients may improve clinicopathological correlations and may serve as a reference for neuropathologists. METHODS: We performed a systematic review on 42 pathological studies to assess the pooled prevalence rates and density (a measure of the number of inclusions per brain region) of (phosphorylated)-TDP-43, p62 and DRP neuronal inclusions in seven brain regions and the spinal cord of 261 C9ORF72-positive patients with amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD) and ALS-FTD. RESULTS: In the cerebellum and hippocampus, the pooled prevalence rates of TDP-43 neuronal cytoplasmic inclusions (NCIs; cerebellum: 3.9%; hippocampus: 68.3%) were lower than those of DRP (cerebellum: 97.2%; hippocampus 97.1%). Moreover, TDP-43 inclusion density was lower compared with p62 inclusion density in these regions. The pooled prevalence rate of TDP-43 NCI in the substantia nigra was high (94.4%). DISCUSSION: The findings of this systematic review largely confirm findings of previous smaller studies on the localization and prevalence of inclusions in the central nervous system of C9ORF72-positive patients. The high prevalence of TDP-43 inclusions in the substantia nigra is a relatively new finding and is probably related to the relatively high prevalence of parkinsonism in C9ORF72-positive patients. PMID- 26373656 TI - Endocrine mucin-producing sweat gland carcinoma of the eyelid. AB - An elderly woman was incidentally noted to have a nodular mass on the upper eyelid, whilst under investigation for cataracts. Punch biopsy of this presumed basal cell carcinoma revealed it to be endocrine mucin-producing sweat gland carcinoma (EMPSGC). The tumour extended to the deep dermal layer and comprised solid nests with foci of cystic and papillary change, and additional cytoplasmic and focal extracellular mucin deposits. Immunohistochemistry confirmed epithelial lineage and neuroendocrine differentiation, and adjacent tissue invasion. The tumour was excised completely with Mohs micrographic surgery with no recurrence after 8 months. EMPSGC is a low-grade sweat gland carcinoma with variable neuroendocrine differentiation, a solid, papillary, or cystic growth pattern, and a predilection for the eyelid of elderly women [Am J Surg Pathol 29:1330-1339, 2005]. There have been 54 previously documented cases of EMPSCG. We report an additional case and review the literature. PMID- 26373657 TI - Longitudinal Care Improves Cessation in Smokers Who Do Not Initially Respond to Treatment by Increasing Cessation Self-Efficacy, Satisfaction, and Readiness to Quit: A Mediated Moderation Analysis. AB - BACKGROUND: The Tobacco Longitudinal Care study was a randomized controlled trial for smoking cessation. It demonstrated that longitudinal care for smoking cessation, in which telephone-based counseling and nicotine replacement therapy were offered for 12 months, was more effective than the standard 8-week treatment. PURPOSE: This study aims to identify for whom and how longitudinal care increased the likelihood of abstinence. METHODS: Mediated moderation analyses were utilized across three time points. RESULTS: There was a trend towards smokers who did not respond to treatment (i.e., were still smoking) by 21 days being more likely to be abstinent at 6 months if they received longitudinal care rather than usual care. Similarly, those who did not respond to treatment by 3 months were more likely to be abstinent at 12 months if they received longitudinal care. At both time points, the likelihood of abstinence did not differ across treatment conditions among participants who responded to treatment (i.e., quit smoking). The effect on 6-month outcomes was mediated by satisfaction and readiness to quit. Cessation self-efficacy, satisfaction, and readiness to quit mediated the effect on 12-month outcomes. The effect of treatment condition on the likelihood of abstinence at 18 months was not moderated by response to treatment at 6 months. CONCLUSIONS: Smokers who did not respond to initial treatment benefited from longitudinal care. Differential effects of treatment condition were not observed among those who responded to early treatment. Conditional assignment to longitudinal care may be useful. Determining for whom and how interventions work over time will advance theory and practice. PMID- 26373658 TI - Phenotypic Plasticity Conditions the Response of Soybean Seed Yield to Elevated Atmospheric CO2 Concentration. AB - Selection for cultivars with superior responsiveness to elevated atmospheric CO2 concentrations (eCO2) is a powerful option for boosting crop productivity under future eCO2. However, neither criteria for eCO2 responsiveness nor prescreening methods have been established. The purpose of this study was to identify traits responsible for eCO2 responsiveness of soybean (Glycine max). We grew 12 Japanese and U.S. soybean cultivars that differed in their maturity group and determinacy under ambient CO2 and eCO2 for 2 years in temperature gradient chambers. CO2 elevation significantly increased seed yield per plant, and the magnitude varied widely among the cultivars (from 0% to 62%). The yield increase was best explained by increased aboveground biomass and pod number per plant. These results suggest that the plasticity of pod production under eCO2 results from biomass enhancement, and would therefore be a key factor in the yield response to eCO2, a resource-rich environment. To test this hypothesis, we grew the same cultivars at low planting density, a resource-rich environment that improved the light and nutrient supplies by minimizing competition. Low planting density significantly increased seed yield per plant, and the magnitude ranged from 5% to 105% among the cultivars owing to increased biomass and pod number per plant. The yield increase due to low-density planting was significantly positively correlated with the eCO2 response in both years. These results confirm our hypothesis and suggest that high plasticity of biomass and pod production at a low planting density reveals suitable parameters for breeding to maximize soybean yield under eCO2. PMID- 26373659 TI - Temperature Responses of C4 Photosynthesis: Biochemical Analysis of Rubisco, Phosphoenolpyruvate Carboxylase, and Carbonic Anhydrase in Setaria viridis. AB - The photosynthetic assimilation of CO2 in C4 plants is potentially limited by the enzymatic rates of Rubisco, phosphoenolpyruvate carboxylase (PEPc), and carbonic anhydrase (CA). Therefore, the activity and kinetic properties of these enzymes are needed to accurately parameterize C4 biochemical models of leaf CO2 exchange in response to changes in CO2 availability and temperature. There are currently no published temperature responses of both Rubisco carboxylation and oxygenation kinetics from a C4 plant, nor are there known measurements of the temperature dependency of the PEPc Michaelis-Menten constant for its substrate HCO3 (-), and there is little information on the temperature response of plant CA activity. Here, we used membrane inlet mass spectrometry to measure the temperature responses of Rubisco carboxylation and oxygenation kinetics, PEPc carboxylation kinetics, and the activity and first-order rate constant for the CA hydration reaction from 10 degrees C to 40 degrees C using crude leaf extracts from the C4 plant Setaria viridis. The temperature dependencies of Rubisco, PEPc, and CA kinetic parameters are provided. These findings describe a new method for the investigation of PEPc kinetics, suggest an HCO3 (-) limitation imposed by CA, and show similarities between the Rubisco temperature responses of previously measured C3 species and the C4 plant S. viridis. PMID- 26373660 TI - Integrated Analysis of Engineered Carbon Limitation in a Quadruple CO2/HCO3- Uptake Mutant of Synechocystis sp. PCC 6803. AB - Cyanobacteria have efficient carbon concentration mechanisms and suppress photorespiration in response to inorganic carbon (Ci) limitation. We studied intracellular Ci limitation in the slow-growing CO2/HCO3 (-)-uptake mutant DeltandhD3 (for NADH dehydrogenase subunit D3)/ndhD4 (for NADH dehydrogenase subunit D4)/cmpA (for bicarbonate transport system substrate-binding protein A)/sbtA (for sodium-dependent bicarbonate transporter A): Delta4 mutant of Synechocystis sp. PCC 6803. When cultivated under high-CO2 conditions, ?4 phenocopies wild-type metabolic and transcriptomic acclimation responses after the shift from high to low CO2 supply. The ?4 phenocopy reveals multiple compensation mechanisms and differs from the preacclimation of the transcriptional Ci regulator mutant ?ndhR (for ndhF3 operon transcriptional regulator). Contrary to the carboxysomeless ?ccmM (for carbon dioxide concentrating mechanism protein M) mutant, the metabolic photorespiratory burst triggered by shifting to low CO2 is not enhanced in ?4. However, levels of the photorespiratory intermediates 2-phosphoglycolate and glycine are increased under high CO2. The number of carboxysomes is increased in ?4 under high-CO2 conditions and appears to be the major contributing factor for the avoidance of photorespiration under intracellular Ci limitation. The ?4 phenocopy is associated with the deregulation of Ci control, an overreduced cellular state, and limited photooxidative stress. Our data suggest multiple layers of Ci regulation, including inversely regulated modules of antisense RNAs and cognate target messenger RNAs and specific trans-acting small RNAs, such as the posttranscriptional PHOTOSYNTHESIS REGULATORY RNA1 (PsrR1), which shows increased expression in ?4 and is involved in repressing many photosynthesis genes at the posttranscriptional level. In conclusion, our insights extend the knowledge on the range of compensatory responses of Synechocystis sp. PCC 6803 to intracellular Ci limitation and may become a valuable reference for improving biofuel production in cyanobacteria, in which Ci is channeled off from central metabolism and may thus become a limiting factor. PMID- 26373661 TI - Maize Homologs of Hydroxycinnamoyltransferase, a Key Enzyme in Lignin Biosynthesis, Bind the Nucleotide Binding Leucine-Rich Repeat Rp1 Proteins to Modulate the Defense Response. AB - In plants, most disease resistance genes encode nucleotide binding Leu-rich repeat (NLR) proteins that trigger a rapid localized cell death called a hypersensitive response (HR) upon pathogen recognition. The maize (Zea mays) NLR protein Rp1-D21 derives from an intragenic recombination between two NLRs, Rp1-D and Rp1-dp2, and confers an autoactive HR in the absence of pathogen infection. From a previous quantitative trait loci and genome-wide association study, we identified a single-nucleotide polymorphism locus highly associated with variation in the severity of Rp1-D21-induced HR. Two maize genes encoding hydroxycinnamoyltransferase (HCT; a key enzyme involved in lignin biosynthesis) homologs, termed HCT1806 and HCT4918, were adjacent to this single-nucleotide polymorphism. Here, we show that both HCT1806 and HCT4918 physically interact with and suppress the HR conferred by Rp1-D21 but not other autoactive NLRs when transiently coexpressed in Nicotiana benthamiana. Other maize HCT homologs are unable to confer the same level of suppression on Rp1-D21-induced HR. The metabolic activity of HCT1806 and HCT4918 is unlikely to be necessary for their role in suppressing HR. We show that the lignin pathway is activated by Rp1-D21 at both the transcriptional and metabolic levels. We derive a model to explain the roles of HCT1806 and HCT4918 in Rp1-mediated disease resistance. PMID- 26373663 TI - [Kyphoplasty-Vertebroplasty. A critical assessment]. AB - CLINICAL ISSUE: Painful vertebral compression fractures. STANDARD TREATMENT: Analgesia. TREATMENT INNOVATIONS: Osteoplastic procedures, such as kyphoplasty and vertebroplasty. DIAGNOSTIC WORKUP: Anamnestic and radiological associations of clinical complaints with the radiomorphological findings of vertebral compression fractures are required for an adequate consideration to assess whether an osteoplastic procedure should be carried out. A computed tomography (CT) scan allows a reliable judgement whether an osteoplastic procedure is technically feasible and promising to improve the local vertebral fracture associated pain. PERFORMANCE: Prospective controlled trials have demonstrated a satisfactory improvement of back pain associated with vertebral fractures and parameters of quality of life by osteoplastic interventions. ACHIEVEMENTS: No prospective, truly sham-controlled blind trials are currently available which demonstrate an advantage of osteoplastic interventions compared to standard pain treatment; however, the currently published prospective controlled trials show a satisfactory pain reduction by osteoplastic interventions, such as kyphoplasty and vertebroplasty. PRACTICAL RECOMMENDATIONS: Painful vertebral fractures and progressive loss of vertebral height of compression fractures should be evaluated in an interdisciplinary team consisting of radiologists, spinal surgeons and internists to assess whether an osteoplastic procedure is technically feasible and promising to improve local pain and immobility associated with vertebral fractures. PMID- 26373662 TI - Map-Based Cloning of Seed Dormancy1-2 Identified a Gibberellin Synthesis Gene Regulating the Development of Endosperm-Imposed Dormancy in Rice. AB - Natural variation in seed dormancy is controlled by multiple genes mapped as quantitative trait loci in major crop or model plants. This research aimed to clone and characterize the Seed Dormancy1-2 (qSD1-2) locus associated with endosperm-imposed dormancy and plant height in rice (Oryza sativa). qSD1-2 was delimited to a 20-kb region, which contains OsGA20ox2 and had an additive effect on germination. Naturally occurring or induced loss-of-function mutations of the gibberellin (GA) synthesis gene enhanced seed dormancy and also reduced plant height. Expression of this gene in seeds (including endospermic cells) during early development increased GA accumulation to promote tissue morphogenesis and maturation programs. The mutant allele prevalent in semidwarf cultivars reduced the seed GA content by up to 2-fold at the early stage, which decelerated tissue morphogenesis including endosperm cell differentiation, delayed abscisic acid accumulation by a shift in the temporal distribution pattern, and postponed dehydration, physiological maturity, and germinability development. As the endosperm of developing seeds dominates the moisture equilibrium and desiccation status of the embryo in cereal crops, qSD1-2 is proposed to control primary dormancy by a GA-regulated dehydration mechanism. Allelic distribution of OsGA20ox2, the rice Green Revolution gene, was associated with the indica and japonica subspeciation. However, this research provided no evidence that the primitive indica- and common japonica-specific alleles at the presumably domestication-related locus functionally differentiate in plant height and seed dormancy. Thus, the evolutionary mechanism of this agriculturally important gene remains open for discussion. PMID- 26373664 TI - Entero-enteric fistula from the stump of an end-to-side ileocolic anastomosis mimicking cancer recurrence. AB - Enteric fistulae are a complex and technically frustrating complication of any bowel surgery. The constellation of associated non-specific symptoms often leads to extensive investigation and, in this case, suspicion of disease recurrence. A 71-year-old gentleman with a history of previous colorectal cancer presented with chronic diarrhoea, weight loss and left lower quadrant pain. Elective exploratory laparoscopy was performed to investigate possible disease recurrence due to elevated carcinoembryonic antigen levels and a positron emission tomography positive area within the mesentery. A jejunal-ileal fistula was found at laparotomy where the blind ileal stump of the end-to-side ileocolic anastomosis had fistulated into the jejunum. Resection of the affected jejunum was performed with end-to-end jejuno-jejunal re-anastomosis and stapling of the ileal stump. Specimen histology was negative for recurrence. Intestinal fistulae represent a diagnostic challenge. This is the first case report describing an enteric fistula mimicking cancer recurrence. PMID- 26373665 TI - Anthocyanin Profile in Berries of Wild and Cultivated Vaccinium spp. along Altitudinal Gradients in the Alps. AB - Vaccinium spp. berries provide some of the best natural sources of anthocyanins. In the wild bilberry (Vaccinium myrtillus L.), a clear increasing trend in anthocyanin biosynthesis has been reported toward northern latitudes of Europe, but studies related to altitude have given contradictory results. The present study focused on the anthocyanin composition in wild bilberries and highbush blueberry (Vaccinium corymbosum L. cv. Brigitta Blue) growing along altitudinal gradients in the Alps of northern Italy. Our results indicate an increasing accumulation of anthocyanins in bilberries along an altitudinal gradient of about 650 m. The accumulation was due to a significant increase in delphinidin and malvidin glycosides, whereas the accumulation of cyanidin and peonidin glycosides was not affected by altitude. Seasonal differences, especially temperature, had a major influence on the accumulation of anthocyanins in blueberries. PMID- 26373666 TI - Family physicians' role in palliative care throughout the care continuum: stakeholder perspectives. AB - BACKGROUND: While palliative care is still often viewed as care for the final stage of life provided usually by specialist health care professionals, ideally, a palliative care approach would start at an earlier stage, with an important role being assigned to the family physician (FP). However, the description of what the FP's tasks would be in the integration of a palliative care approach into the care continuum remains vague. OBJECTIVE: To explore the views of FPs, nurses and patients about the tasks of the FP in palliative care for people with a life-limiting illness from diagnosis onwards. METHODS: We performed 18 interviews with people with cancer, organ failure or dementia and 6 focus groups, 4 with FPs and 2 with community nurses. Analysis was guided by a thematic content analysis procedure to categorize perceived tasks into overarching themes. RESULTS: The tasks attributed to the FP could be categorized into four roles: FP as (i) available medical expert, (ii) communicator, (iii) collaborator and (iv) life-long learner committed to improving their palliative care competencies by training. Some perceived tasks varied depending on the different phases of illness (such as around diagnosis), while others were applicable throughout the whole illness course. Participants mostly had the same perception of the FPs' tasks, but there was disagreement on, for example, the timing of care planning. CONCLUSION: Our results help to elucidate the tasks and roles required of FPs to make integration of a palliative care approach into the care continuum possible. PMID- 26373667 TI - Hymenobacter terrenus sp. nov., isolated from biological soil crusts. AB - A Gram-stain-negative, non-spore-forming, short rod-shaped, non-motile, light pink bacterial strain, MIMtkLc17T, was isolated from biological soil crusts collected in Liangcheng, Inner Mongolia. Growth of strain MIMtkLc17T was observed at 2-35 degrees C and in the presence of 1% (w/v) NaCl. Phylogenetic analysis of 16S rRNA gene sequences showed that sequence similarities between strain MIMtkLc17T and the type strains of species of the genus Hymenobacter ranged from 89.93% to 96.49%. Strain MIMtkLc17T can secrete mass polysaccharide. The major fatty acids of strain MIMtkLc17T were iso-C15 : 0, summed feature 3 (C16 : 1omega7c/C16 : 1omega6c), C16 : 1omega5c and summed feature 4 (iso-C17 : 1 I/anteiso-C17 : 1 B). The sole respiratory quinone was menaquinone MK-7. The G+C content of the chromosomal DNA was 57.8 mol%. The results of phylogenetic, chemotaxonomic and phenotypic characterization indicated that strain MIMtkLc17T can be distinguished from all known species of the genus Hymenobacter and represents a novel species of this genus, for which the name Hymenobacter terrenus sp. nov. is proposed. The type strain is MIMtkLc17T ( = MCCC 1K00507T = KCTC 42636T). PMID- 26373668 TI - Intraoperative neurophysiological monitoring for the resection of brain tumors in pediatric patients. AB - Intraoperative neurophysiology (ION) is the gold standard to map and monitor brain functions during supratentorial surgery in critical areas. This is of great value for the surgery of brain gliomas in adults, but the same ION techniques can be used in the pediatric population with respect to both epilepsy and brain tumor surgery. While the principles of most ION techniques are the same for adults and children, the developing nervous system has peculiar characteristics in terms of anatomical and physiological maturation of afferent and efferent pathways within the brain and the spinal cord. Accordingly, some adjustments, particularly with regards to stimulation parameters, are needed in younger children. This paper will review current ION techniques to assist during the resection of brain tumors in children, focusing on the aspects peculiar to mapping and monitoring of sensori-motor functions in the pediatric population. On the other hand, awake surgery, of common use in adult patients when aiming to identify cortical and subcortical cognitive functions, is of very limited use in children and will not be discussed here. PMID- 26373669 TI - Newer endovascular tools: a review of experimental and clinical aspects. AB - The history of treatment of intracranial aneurysms dates back to the late 18th century. These early physicians largely based their crude techniques around "wire insertion alone, galvanopuncture (electrothrombosis), and fili-galvanopuncture (wire insertion together with electrothrombosis)," albeit with overwhelmingly unfavorable outcomes. By the end of the 20th century, treatment options progressed to include two highly effective, and safe, procedures: surgical clipping and endovascular coiling. These methods have been found to be effective treatments for a large portion of aneurysms, but there still exists a subset of patients that do not respond well to these therapies. While much progress has been made in stent-assisted coiling including the development of newer stents aimed at keep the coil ball from protruding into the parent vessel, the introduction of flow diverters has characterized a new phase in the endovascular treatment of intracranial aneurysms. This treatment paradigm is rapidly becoming the treatment of choice for large and complex aneurysms internal carotid artery. Intrasaccular flow diverters such as the Woven EndoBridge device (WEB) and Luna device are showing promise in the treatment of wide neck bifurcation aneurysms. Other newer devices including the pCONus Bifurcating Aneurysm Implant and Endovascular Clip Systems (eCLIPs) are showing promise in small clinical and preclinical studies. As technology improves, newer devices with ingenious designs are constantly being introduced into the clinical arena. Most of these devices try to address the limitations of traditional endovascular methods in regard to providing a safe and effective treatment of wide-necked bifurcation aneurysms. Several large prospective studies are underway and once completed, the role of these newer devices will be better defined. It is easy to anticipate that with advances in 3D techniques and printing, a future in which customized devices are designed based on the individual anatomy and morphology of the aneurysm in a given patient is within reach. PMID- 26373670 TI - High-resolution analysis of the m-xylene/toluene biodegradation subtranscriptome of Pseudomonas putida mt-2. AB - Pseudomonas putida mt-2 metabolizes m-xylene and other aromatic compounds through the enzymes encoded by the xyl operons of the TOL plasmid pWW0 along with other chromosomally encoded activities. Tiling arrays of densely overlapping oligonucleotides were designed to cover every gene involved in this process, allowing dissection of operon structures and exposing the interplay of plasmid and chromosomal functions. All xyl sequences were transcribed in response to aromatic substrates and the 3'-termini of both upper and lower mRNA operons extended beyond their coding regions, i.e. the 3'-end of the lower operon mRNA penetrated into the convergent xylS regulatory gene. Furthermore, xylR mRNA for the master m-xylene responsive regulator of the system was decreased by aromatic substrates, while the cognate upper operon mRNA was evenly stable throughout its full length. RNA sequencing confirmed these data at a single nucleotide level and refined the formerly misannotated xylL sequence. The chromosomal ortho route for degradation of benzoate (the ben, cat clusters and some pca genes) was activated by this aromatic, but not by the TOL substrates, toluene or m-xylene. We advocate this scenario as a testbed of natural retroactivity between a pre-existing metabolic network and a new biochemical pathway implanted through gene transfer. PMID- 26373671 TI - Genetic evidence for a Smoothened-Galpha(i) signaling axis in mammals. AB - In this issue of Science Signaling, Villanueva et al. report on the identification of heterotrimeric guanine nucleotide-binding protein (G protein) Galphai2 as an essential effector of Smoothened-mediated mammary epithelial cell proliferation. Through a series of in vivo experiments, the authors delineate a Smoothened-regulated Gli-independent Galphai signal that provides direct genetic evidence connecting Smoothened with Galphai in mice. PMID- 26373672 TI - An essential role for Galpha(i2) in Smoothened-stimulated epithelial cell proliferation in the mammary gland. AB - Hedgehog (Hh) signaling is critical for organogenesis, tissue homeostasis, and stem cell maintenance. The gene encoding Smoothened (SMO), the primary effector of Hh signaling, is expressed aberrantly in human breast cancer, as well as in other cancers. In mice that express a constitutively active form of SMO that does not require Hh stimulation in mammary glands, the cells near the transgenic cells proliferate and participate in hyperplasia formation. Although SMO is a seven transmembrane receptor like G protein-coupled receptors (GPCRs), SMO-mediated activation of the Gli family of transcription factors is not known to involve G proteins. However, data from Drosophila and mammalian cell lines indicate that SMO functions as a GPCR that couples to heterotrimeric G proteins of the pertussis toxin (PTX)-sensitive Galphai class. Using genetically modified mice, we demonstrated that SMO signaling through G proteins occurred in the mammary gland in vivo. SMO-induced stimulation of proliferation was PTX-sensitive and required Galphai2, but not Galphai1, Galphai3, or activation of Gli1 or Gli2. Our findings show that activated SMO functions as a GPCR to stimulate proliferation in vivo, a finding that may have clinical importance because most SMO-targeted agents have been selected based largely on their ability to block Gli-mediated transcription. PMID- 26373673 TI - B cell antigen receptors of the IgM and IgD classes are clustered in different protein islands that are altered during B cell activation. AB - The B cell antigen receptors (BCRs) play an important role in the clonal selection of B cells and their differentiation into antibody-secreting plasma cells. Mature B cells have both immunoglobulin M (IgM) and IgD types of BCRs, which have identical antigen-binding sites and are both associated with the signaling subunits Igalpha and Igbeta, but differ in their membrane-bound heavy chain isoforms. By two-color direct stochastic optical reconstruction microscopy (dSTORM), we showed that IgM-BCRs and IgD-BCRs reside in the plasma membrane in different protein islands with average sizes of 150 and 240 nm, respectively. Upon B cell activation, the BCR protein islands became smaller and more dispersed such that the IgM-BCRs and IgD-BCRs were found in close proximity to each other. Moreover, specific stimulation of one class of BCR had minimal effects on the organization of the other. These conclusions were supported by the findings from two-marker transmission electron microscopy and proximity ligation assays. Together, these data provide evidence for a preformed multimeric organization of BCRs on the plasma membrane that is remodeled after B cell activation. PMID- 26373674 TI - Systematic profiling of the bacterial phosphoproteome reveals bacterium-specific features of phosphorylation. AB - Protein phosphorylation is a crucial posttranslational modification for regulating cellular processes in bacteria; however, it has not been extensively studied because of technical difficulties in the enrichment of phosphopeptides. We devised an enrichment protocol that enabled the identification of >1000 phosphopeptides from a single bacterial sample. We discovered three high confidence serine and threonine phosphorylation motifs, as well as 29 other motifs at various levels of confidence, from three distinct bacterial phosphoproteomes. We found that the proline-directed and basophilic phosphorylation motifs that are commonly enriched in eukaryotes were not observed in bacteria. Unlike eukaryotes, bacteria had a low occurrence of both phosphorylation and acetylation in N-terminal phosphopeptides. Because infection of host cells by bacterial pathogens is often accompanied by kinase-mediated phosphorylation events, the differences in phosphorylation preferences between bacteria and eukaryotes revealed by this study could be useful in identifying bacterial-specific targets for future therapies. PMID- 26373675 TI - Comparison of techniques for volumetric analysis of the future liver remnant: implications for major hepatic resections. AB - OBJECTIVE: The purpose of this work was to compare measured and estimated volumetry prior to liver resection. METHODS: Data for consecutive patients submitted to major liver resection for colorectal liver metastases at two centres during 2004-2012 were reviewed. All patients underwent volumetric analysis to define the measured total liver volume (mTLV) and measured future liver remnant ratio (mR(FLR)). The estimated total liver volume (eTLV) standardized to body surface area and estimated future liver remnant ratio (eR(FLR)) were calculated. Descriptive statistics were generated and compared. A difference between mR(FLR) and eR(FLR) of +/-5% was considered clinically relevant. RESULTS: Data for a total of 116 patients were included. All patients underwent major resection and 51% underwent portal vein embolization. The mean difference between mTLV and eTLV was 157 ml (P < 0.0001), whereas the mean difference between mR(FLR) and eR(FLR) was -1.7% (P = 0.013). By linear regression, eTLV was only moderately predictive of mTLV (R(2) = 0.35). The distribution of differences between mR(FLR) and eR(FLR) demonstrated that the formula over- or underestimated mR(FLR) by >=5% in 31.9% of patients. CONCLUSIONS: Measured and estimated volumetry yielded differences in the FLR of >=5% in almost one-third of patients, potentially affecting clinical decision making. Estimated volumetry should be used cautiously and cannot be recommended for general use. PMID- 26373676 TI - MYC-IG rearrangements are negative predictors of survival in DLBCL patients treated with immunochemotherapy: a GELA/LYSA study. AB - Diffuse large B-cell lymphoma (DLBCL) with MYC rearrangement (MYC-R) carries an unfavorable outcome. We explored the prognostic value of the MYC translocation partner gene in a series of MYC-R de novo DLBCL patients enrolled in first-line prospective clinical trials (Groupe d'Etudes des Lymphomes de l'Adulte/Lymphoma Study Association) and treated with rituximab-anthracycline-based chemotherapy. A total of 774 DLBCL cases characterized for cell of origin by the Hans classifier were analyzed using fluorescence in situ hybridization with BCL2, BCL6, MYC, immunoglobulin (IG)K, and IGL break-apart and IGH/MYC, IGK/MYC, and IGL/MYC fusion probes. MYC-R was observed in 51/574 (8.9%) evaluable DLBCL cases. MYC-R cases were predominantly of the germinal center B-cell-like subtype 37/51 (74%) with no distinctive morphologic and phenotypic features. Nineteen cases were MYC single-hit and 32 cases were MYC double-hit (MYC plus BCL2 and/or BCL6) DLBCL. MYC translocation partner was an IG gene in 24 cases (MYC-IG) and a non-IG gene (MYC-non-IG) in 26 of 50 evaluable cases. Noteworthy, MYC-IG patients had shorter overall survival (OS) (P = .0002) compared with MYC-negative patients, whereas no survival difference was observed between MYC-non-IG and MYC-negative patients. In multivariate analyses, MYC-IG predicted poor progression-free survival (P = .0051) and OS (P = .0006) independently from the International Prognostic Index and the Hans classifier. In conclusion, we show in this prospective randomized trial that the adverse prognostic impact of MYC-R is correlated to the MYC-IG translocation partner gene in DLBCL patients treated with immunochemotherapy. These results may have an important impact on the clinical management of DLBCL patients with MYC-R who should be routinely characterized according to MYC partner gene. These trials are individually registered at www.clinicaltrials.gov as #NCT00144807, #NCT01087424, #NCT00169143, #NCT00144755, #NCT00140660, #NCT00140595, and #NCT00135499. PMID- 26373677 TI - Has bioscience reconciled mind and body? AB - AIMS AND OBJECTIVES: The aim of this discursive paper is to explore the question 'has biological science reconciled mind and body?'. BACKGROUND: This paper has been inspired by the recognition that bioscience has a historical reputation for privileging the body over the mind. The disregard for the mind (emotions and behaviour) cast bioscience within a 'mind-body problem' paradigm. It has also led to inherent limitations in its capacity to contribute to understanding the complex nature of health. DESIGN: This is a discursive paper. METHODS: Literature from the history and sociology of science and psychoneuroimmunology (1975-2015) inform the arguments in this paper. The historical and sociological literature provides the basis for a socio-cultural debate on mind-body considerations in science since the 1970s. The psychoneuroimmunology literature draws on mind-body bioscientific theory as a way to demonstrate how science is reconciling mind and body and advancing its understanding of the interconnections between emotions, behaviour and health. RESULTS: Using sociological and biological evidence, this paper demonstrates how bioscience is embracing and advancing its understanding of mind-body interconnectedness. It does this by demonstrating the emotional and behavioural alterations that are caused by two common phenomena; prolonged, chronic peripheral inflammation and prolonged psychological stress. The evidence and arguments provided has global currency that advances understanding of the inter-relationship between emotions, behaviour and health. CONCLUSIONS: This paper shows how bioscience has reconciled mind and body. In doing so, it has advanced an understanding of science's contribution to the inter-relationship between emotions, behaviour and health. RELEVANCE TO CLINICAL PRACTICE: The biological evidence supporting mind-body science has relevance to clinical practice for nurses and other healthcare professions. This paper discusses how this evidence can inform and enhance clinical practice directly and through research, education and policy. PMID- 26373679 TI - Aromatic hydroxylation using an oxo-bridged diiron(III) complex: a bio-inspired functional model of toluene monooxygenases. AB - In biology, aromatic hydroxylation is carried out using a family of heme and nonheme oxygenases, such as cytochrome P450, toluene monooxygenases (TMOs), and methane monooxygenase (MMO). In contrast, a vast majority of synthetic iron based catalysts employed so far in aromatic hydroxylation are monomeric in nature. Herein, we have employed a diferric complex of an aminopyridine ligand ([(bpmen)2Fe2O(MU-O)(MU-OH)](ClO4)3 (2), bpmen = N,N'-dimethyl-N,N'-bis(2 pyridylmethyl)-1,2-diaminoethane) towards aromatic hydroxylation with H2O2 and acetic acid. The diiron(iii) complex shows promising reactivity in the hydroxylation of benzene and alkylbenzenes with a higher selectivity towards aromatic ring hydroxylation over alkyl chain oxidation. The MU-oxo diiron(iii) core has been shown to be regenerated at the end of catalytic turnover. However, mechanistic studies indicate that the diiron(iii) complex undergoes dissociation into its monomeric congener and the resulting iron(iii) complex mitigates aromatic hydroxylation. PMID- 26373678 TI - Nanobody-targeted E3-ubiquitin ligase complex degrades nuclear proteins. AB - Targeted protein degradation is a powerful tool in determining the function of specific proteins or protein complexes. We fused nanobodies to SPOP, an adaptor protein of the Cullin-RING E3 ubiquitin ligase complex, resulting in rapid ubiquitination and subsequent proteasome-dependent degradation of specific nuclear proteins in mammalian cells and zebrafish embryos. This approach is easily modifiable, as substrate specificity is conferred by an antibody domain that can be adapted to target virtually any protein. PMID- 26373680 TI - Two porous luminescent metal-organic frameworks: quantifiable evaluation of dynamic and static luminescent sensing mechanisms towards Fe(3.). AB - Two novel porous luminescent metal-organic frameworks (MOFs, 1 and 2) have been constructed using 3,4-di(3,5-dicarboxyphenyl)phthalic acid using a hydrothermal method. Both MOFs can work as highly sensitive sensors to Fe(3+) by luminescent quenching. Analyses of the structures indicate a higher quenching efficiency of 2 because of the existence of active -COOH groups. Based on this consideration, the quenching mechanisms are studied and the processes are controlled by multiple mechanisms in which dynamic and static mechanisms of MOFs are discussed. Besides, the corresponding dynamic and static quenching constants are calculated, achieving the quantification evaluation of the quenching process. As expected, experimental data show that compound 2 possesses an overall quenching efficiency 6.9 times that of compound 1. Additionally, time-dependent intensity measurements, the shifts of the excitation spectrum and the appearance of a new emission peak all give visual proofs of the distinct mechanisms between the two MOFs. PMID- 26373682 TI - Successfully treated severe obstetric sepsis and acute respiratory distress syndrome with extracorporeal membrane oxygenation. AB - We report a unique clinical case about an 18-year-old woman, immediately post partum after an urgent C-section, who survived severe sepsis, acute respiratory distress syndrome (ARDS) and disseminated intravascular coagulation (DIC) and was successfully treated with 11 different antibiotics, massive blood transfusions and repetitive surgeries and was on extracorporeal membrane oxygenation (ECMO) support for 22 days. Although, ECMO is a time-limited procedure and most manufacturers do not advise more than 14 days of use, the situation for this patient was life-threatening and ECMO, despite the dangerous risks listed above, was the only way to win time for the lungs to recover and for treatment of the underlying disease, while maintaining adequate oxygenation and circulation. Fortunately, the condition of this woman was stabilized and she achieved complete physical recovery, despite minor neurological deficit in the fingers of her right hand. PMID- 26373683 TI - Genome-wide screen of promoter methylation analysis of ES cells and ES derived epidermal-like cells. AB - Embryonic stem cells (ESCs) are a population of pluripotent cells which can differentiate into different cell types. However, there are few reports with regard to differentiate ESCs into epidermal cells in vitro. In this study, we aimed to investigate differentially methylated promoters involved in process of differentiation from ESCs into epidermal-like cells (ELCs) induced by human amnion. We successfully induced ESCs into ELCs, which expressed the surface markers of CK19, CK15 and beta1-integrin. With MeDIP-chip arrays, we identified 3435 gene promoters to be differentially methylated, involving 894 HCP (high CpG containing promoter), 974 ICP (intermediate CpG-containing promoter) and 1567 LCP (low CpG-containing promoter) among all the 17,500 DNA methylation regions of gene promoters in both ESCs and ELCs. Gene oncology and pathway analysis demonstrated that these genes were involved in all the three categories of GO enrichment analysis, including biological process, molecular function and cellular component. All these data suggested that embryonic stem cells can differentiate into epidermal-like cells and promoter methylation is of great importance in this process. PMID- 26373684 TI - Polarization dependent photocurrent in the Bi2Te3 topological insulator film for multifunctional photodetection. AB - Three dimensional Z2 Topological insulator (TI) is an unconventional phase of quantum matter possessing insulating bulk state as well as time-reversal symmetry protected Dirac-like surface state, which is demonstrated by extensive experiments based on surface sensitive detection techniques. This intriguing gapless surface state is theoretically predicted to exhibit many exotic phenomena when interacting with light, and some of them have been observed. Herein, we report the first experimental observation of novel polarization dependent photocurrent of photodetectors based on the TI Bi2Te3 film under irradiation of linearly polarized light. This photocurrent is linearly dependent on both the light intensity and the applied bias voltage. To pursue the physical origin of the polarization dependent photocurrent, we establish the basic TI surface state model to treat the light irradiation as a perturbation, and we adopt the Boltzmann equation to calculate the photocurrent. It turns out that the theoretical results are in nice qualitative agreement with the experiment. These findings show that the polycrystalline TI Bi2Te3 film working as a multifunctional photodetector can not only detect the light intensity, but also measure the polarization state of the incident light, which is remarkably different from conventional photodetectors that usually only detect the light intensity. PMID- 26373685 TI - Surfactant-Templated Synthesis of Polypyrrole Nanocages as Redox Mediators for Efficient Energy Storage. AB - Preparation of conducting-polymer hollow nanoparticles with different diameters was accomplished by surfactant templating. An anionic surfactant, namely sodium dodecylbenzenesulfonate, formed vesicles to template with the pyrrole monomer. Subsequent chemical oxidative polymerization of the monomer yielded spherical polypyrrole (PPy) nanoparticles with hollow interiors. The diameter of the hollow nanoparticles was easily controlled by adjusting the concentration of the surfactant. Subsequently, the size-dependent electrochemical properties of the nanoparticles, including redox properties and charge/discharge behavior, were examined. By virtue of the structural advantages, the specific capacitance (max. 326 F g(-1)) of PPy hollow nanoparticles was approximately twice as large as that of solid PPy nanospheres. The hollow PPy nanostructure can easily be used as a conductive substrate for the preparation of metal/polymer nanohybrids through chemical and electrochemical deposition. Two different pseudocapacitive metal oxide clusters were readily deposited on the inner and outer surfaces of the hollow nanoparticles, which resulted in an increase in the specific capacitance to 390 F g(-1). In addition, the hollow nanoparticles acted as a nanocage to prevent metal ion leaching during charge/discharge, thus allowing an excellent capacitance retention of ca. 86%, even following 10,000 cycles. PMID- 26373687 TI - Measuring breathing patterns and respiratory movements with the respiratory movement measuring instrument. AB - INTRODUCTION: The respiratory movement measuring instrument (RMMI) is a laser based non-invasive technique to measure breathing patterns and respiratory movements (RMs). Little knowledge is known about the ability of the RMMI to measure breathing patterns and the correlation between RMs and breathing volumes. OBJECTIVES: One aim was to investigate whether the RMMI could discriminate between normal versus abdominal versus high costal breathing patterns in different body positions. A second aim was to determine the correlation between RMs and breathing volumes in different body positions. METHOD: Twenty adult, healthy subjects (10 women) were included in the study. The RMMI was used to study the above-mentioned breathing patterns in supine, sitting and standing positions. A subgroup of 12 subjects (6 women) simultaneously performed measurements of breathing volumes while RMs were recorded. RESULTS: The RMMI was able to discriminate between different breathing patterns in different body positions (P<0.001). The upper thoracic contribution to RMs in the sitting position was 47% for natural breathing, 32% for abdominal breathing and 64% for high costal breathing; similar results were found in the supine and standing positions. A strong correlation was observed between RMs as measured by the RMMI and different breathing volumes in all three body positions (Spearman's rho 0.86 1.00). CONCLUSION: The RMMI can be used to measure and analyse different breathing patterns in different body positions, and the correlation between measured RMs and breathing volumes is strong. PMID- 26373688 TI - Ultrafast optical modification of exchange interactions in iron oxides. AB - Ultrafast non-thermal manipulation of magnetization by light relies on either indirect coupling of the electric field component of the light with spins via spin-orbit interaction or direct coupling between the magnetic field component and spins. Here we propose a scenario for coupling between the electric field of light and spins via optical modification of the exchange interaction, one of the strongest quantum effects with strength of 10(3) Tesla. We demonstrate that this isotropic opto-magnetic effect, which can be called inverse magneto-refraction, is allowed in a material of any symmetry. Its existence is corroborated by the experimental observation of terahertz emission by spin resonances optically excited in a broad class of iron oxides with a canted spin configuration. From its strength we estimate that a sub-picosecond modification of the exchange interaction by laser pulses with fluence of about 1 mJ cm(-2) acts as a pulsed effective magnetic field of 0.01 Tesla. PMID- 26373689 TI - AMP-activated protein kinase couples 3-bromopyruvate-induced energy depletion to apoptosis via activation of FoxO3a and upregulation of proapoptotic Bcl-2 proteins. AB - Most tumors primarily rely on glycolysis rather than mitochondrial respiration for ATP production. This phenomenon, also known as Warburg effect, renders tumors more sensitive to glycolytic disturbances compared to normal cells. 3 bromopyruvate is a potent inhibitor of glycolysis that shows promise as an anticancer drug candidate. Although investigations revealed that 3-BP triggers apoptosis through ATP depletion and subsequent AMPK activation, the underlying molecular mechanisms coupling AMPK to apoptosis are poorly understood. We showed that 3-BP leads to a rapid ATP depletion which was followed by growth inhibition and Bax-dependent apoptosis in HCT116 cells. Apoptosis was accompanied with activation of caspase-9 and -3 while pretreatment with a general caspase inhibitor attenuated cell death. AMPK, p38, JNK, and Akt were phosphorylated immediately upon treatment. Pharmacological inhibition and silencing of AMPK largely inhibited 3-BP-induced apoptosis and reversed phosphorylation of JNK. Transcriptional activity of FoxO3a was dramatically increased subsequent to AMPK mediated phosphorylation of FoxO3a at Ser413. Cell death analysis of cells transiently transfected with wt or AMPK-phosphorylation-deficient FoxO3 expression plasmids verified the contributory role of AMPK-FoxO3a axis in 3-BP induced apoptosis. In addition, expression of proapoptotic Bcl-2 proteins Bim and Bax were upregulated in an AMPK-dependent manner. Bim was transcriptionally activated in association with FoxO3a activity, while Bax upregulation was abolished in p53-null cells. Together, these data suggest that AMPK couples 3-BP induced metabolic disruption to intrinsic apoptosis via modulation of FoxO3a-Bim axis and Bax expression. (c) 2015 Wiley Periodicals, Inc. PMID- 26373690 TI - Levels of helminth infection in the flat lizard Tropidurus semitaeniatus from north-eastern Brazil. AB - Parasites represent a great, unknown component of animal biodiversity. Recent efforts have begun to uncover patterns of infection by helminth parasites in several Neotropical lizards. The present study reports, for the first time, levels of helminth infection in a population of the flat lizard Tropidurus semitaeniatus. One hundred and thirty-nine lizards were examined and evidence of five intestinal helminth species was found, comprising four species of nematodes, one species of cestode and an unidentified encysted larval nematode. The most frequently occurring species was the intestinal nematode Parapharyngodon alvarengai, which did not exhibit differences in prevalence and intensity of infection relative to host sex or age/body size. Furthermore, helminth species richness was not related to host body size. PMID- 26373693 TI - Erosive pustular dermatosis of the scalp induced by ingenol mebutate. PMID- 26373694 TI - Structural, Biochemical, and Computational Studies Reveal the Mechanism of Selective Aldehyde Dehydrogenase 1A1 Inhibition by Cytotoxic Duocarmycin Analogues. AB - Analogues of the natural product duocarmycin bearing an indole moiety were shown to bind aldehyde dehydrogenase 1A1 (ALDH1A1) in addition to DNA, while derivatives without the indole solely addressed the ALDH1A1 protein. The molecular mechanism of selective ALDH1A1 inhibition by duocarmycin analogues was unraveled through cocrystallization, mutational studies, and molecular dynamics simulations. The structure of the complex shows the compound embedded in a hydrophobic pocket, where it is stabilized by several crucial pi-stacking and van der Waals interactions. This binding mode positions the cyclopropyl electrophile for nucleophilic attack by the noncatalytic residue Cys302, thereby resulting in covalent attachment, steric occlusion of the active site, and inhibition of catalysis. The selectivity of duocarmycin analogues for ALDH1A1 is unique, since only minor alterations in the sequence of closely related protein isoforms restrict compound accessibility. PMID- 26373697 TI - Erratum: Genome analysis of Excretory/Secretory proteins in Taenia solium reveals their Abundance of Antigenic Regions (AAR). PMID- 26373696 TI - Efficacy of a Text Message-Delivered Extended Contact Intervention on Maintenance of Weight Loss, Physical Activity, and Dietary Behavior Change. AB - BACKGROUND: Extending contact with participants after the end of an initial intervention is associated with successful maintenance of weight loss and behavior change. However, cost-effective methods of extending intervention contact are needed. OBJECTIVE: This study investigated whether extended contact via text message was efficacious in supporting long-term weight loss and physical activity and dietary behavior change in breast cancer survivors. METHODS: Following the end of an initial 6-month randomized controlled trial of a telephone-delivered weight loss intervention versus usual care, eligible and consenting intervention participants received a 6-month extended contact intervention via tailored text messages targeting a range of factors proposed to influence the maintenance of behavior change. In this single-group, pre-post designed study, within group changes in weight, moderate-to-vigorous physical activity (Actigraph GT3X+ accelerometers), and total energy intake (2x24 hour dietary recalls) were evaluated from baseline to end of initial intervention (6 months), end of extended contact intervention (12 months), and after a no-contact follow-up (18 months) via linear mixed models. Feasibility of implementation was assessed through systematic tracking of text message delivery process outcomes, and participant satisfaction was assessed through semistructured interviews. RESULTS: Participants at baseline (n=29) had a mean age of 54.9 years (SD 8.8), body mass index of 30.0 kg/m(2) (SD 4.2), and were recruited a mean 16.6 months (SD 3.2) post diagnosis. From baseline to 18 months, participants showed statistically significantly lower mean weight (-4.2 kg [95% CI -6.0 to -2.4]; P<.001) and higher physical activity (mean 10.4 mins/day [95% CI 3.6-17.2]; P=.003), but no significant differences in energy intake (P=.200). Participants received a mean of 8 text messages every 2 weeks (range 2-11) and reported a high rate of satisfaction. CONCLUSIONS: In comparison to interventions without extended contact, results suggest text message-delivered extended contact may support the attenuation of weight regain and promote the maintenance of physical activity. PMID- 26373699 TI - Dublin Pathology 2015. 8th Joint Meeting of the British Division of the International Academy of Pathology and the Pathological Society of Great Britain & Ireland, 23-25 June 2015. PMID- 26373698 TI - The phenotype of the musculocontractural type of Ehlers-Danlos syndrome due to CHST14 mutations. AB - The musculocontractural type of Ehlers-Danlos syndrome (MC-EDS) has been recently recognized as a clinical entity. MC-EDS represents a differential diagnosis within the congenital neuromuscular and connective tissue disorders spectrum. Thirty-one and three patients have been reported with MC-EDS so far with bi allelic mutations identified in CHST14 and DSE, respectively, encoding two enzymes necessary for dermatan sulfate (DS) biosynthesis. We report seven additional patients with MC-EDS from four unrelated families, including the follow-up of a sib-pair originally reported with the kyphoscoliotic type of EDS in 1975. Brachycephaly, a characteristic facial appearance, an asthenic build, hyperextensible and bruisable skin, tapering fingers, instability of large joints, and recurrent formation of large subcutaneous hematomas are always present. Three of seven patients had mildly elevated serum creatine kinase. The oldest patient was blind due to retinal detachment at 45 years and died at 59 years from intracranial bleeding; her affected brother died at 28 years from fulminant endocarditis. All patients in this series harbored homozygous, predicted loss-of-function CHST14 mutations. Indeed, DS was not detectable in fibroblasts from two unrelated patients with homozygous mutations. Patient fibroblasts produced higher amounts of chondroitin sulfate, showed intracellular retention of collagen types I and III, and lacked decorin and thrombospondin fibrils compared with control. A great proportion of collagen fibrils were not integrated into fibers, and fiber bundles were dispersed into the ground substance in one patient, all of which is likely to contribute to the clinical phenotype. This report should increase awareness for MC-EDS. PMID- 26373700 TI - Quality-of-life outcomes following pelvic exenteration for primary rectal cancer. AB - BACKGROUND: For patients with locally advanced tumours and contiguous organ involvement, pelvic exenteration (PE) can offer cure with relatively low mortality. The literature surrounding quality of life (QoL) in patients undergoing PE is limited. Furthermore, there are no matched comparisons of QoL between abdominoperineal resection (APR) and PE. The aim of this study was to compare differences in long-term QoL for patients with primary rectal cancer undergoing APR versus PE. METHODS: All patients who underwent either APR or PE between January 2011 and December 2012 were identified. Patients were asked to complete the European Organization for Research and Treatment of Cancer QLQ-C30 questionnaire before surgery and 2 weeks afterwards. Subsequent questionnaires were requested at 3, 6, 12 and 24 months after operation. RESULTS: A total of 110 patients were included in the study (54 APR, 56 PE). Median length of stay following operation was 11 (range 3-70) days for APR and 15 (7-84) days for PE. Patients undergoing PE experienced lower physical (mean score 42 versus 56; P = 0.010), role (20 versus 33; P = 0.047), emotional (57 versus 73; P = 0.010) and social (34 versus 52; P = 0.005) functional levels 2 weeks after surgery. Long term dyspnoea and financial worries were experienced only after PE. Patients undergoing PE had a lower overall global health status at 2 weeks after operation (40 versus 53; P = 0.012). Levels were comparable between groups from 3 months after surgery. CONCLUSION: QoL recovery following PE was equivalent to that after APR alone. Patients should not be denied exenterative surgery based on perceived poor QoL. PMID- 26373702 TI - Letter to the Editor. PMID- 26373701 TI - Relationship of insulin dynamics to body composition and resting energy expenditure following weight loss. AB - OBJECTIVE: To examine associations of baseline insulin dynamics with changes in body composition and resting energy expenditure (REE) following weight loss. METHODS: Twenty-one participants with overweight or obesity achieved 10-15% weight loss and then received 3 weight loss maintenance diets (high-carbohydrate, moderate-carbohydrate, and low-carbohydrate) in random order, each for 4 weeks. Body composition was measured at baseline and after weight loss. Insulin 30 min after glucose consumption (insulin-30; insulin response), C-peptide deconvolution analysis, HOMA, hepatic insulin sensitivity (IS), and REE were assessed at baseline and after each maintenance diet. RESULTS: Insulin-30, but not maximal insulin secretion, hepatic IS, or HOMA, predicted changes in fat mass (standardized beta = 0.385, 1.7 kg difference between 10th and 90th centile of insulin-30, P = 0.04) after weight loss. Insulin-30 (beta = -0.341, -312 kcal day(-1) , P = 0.008), maximal insulin secretion (beta = -0.216, -95 kcal day(-1) , P = 0.0002), HOMA (beta = -0.394, -350 kcal day(-1) , P = 0.002), and hepatic IS (beta = 0.217, 225 kcal day(-1) , P = 0.0003) predicted change in REE during weight loss maintenance, independent of changes in body composition. The inverse relationship between insulin-30 and REE was substantially attenuated when the low carbohydrate diet was consumed first. CONCLUSIONS: These findings distinguish a novel phenotype, characterized by high insulin response, at risk for weight regain, and identify a dietary approach to ameliorate this risk. PMID- 26373703 TI - Nonsuicidal Self-injury as a Risk Factor for Purging Onset: Negatively Reinforced Behaviours that Reduce Emotional Distress. AB - Both nonsuicidal self-injury (NSSI) and purging behaviour are thought to involve harm to the self. The acquired capability for self-harm model holds that engaging in one self-harming behaviour increases the capability to tolerate harm to the self, thus increasing risk for engaging on other such behaviours. In addition, both behaviours are thought to serve the similar function of relief from distress. We thus tested whether engagement in one of these behaviours predicts the subsequent onset of the other. In a longitudinal design, 1158 first-year college women were assessed for purging and NSSI at two time points. Engagement in NSSI at time 1 predicted the college onset of purging behaviour 9 months later (OR = 2.20, p < .04, CI = 1.07-4.19) beyond prediction from time 1 binge behaviour, and purging behaviour at time 1 predicted the subsequent onset of NSSI (OR = 6.54, p < .01, CI = 1.71-25.04). These findings are consistent with the acquired capability for harm model and with the possibility that the two behaviours serve a similar function. PMID- 26373704 TI - Lipid composition has significant effect on targeted drug delivery properties of NGR-modified liposomes. AB - The Asn-Gly-Arg (NGR) motif has previously been demonstrated to specifically bind to CD13, which is selectively overexpressed in tumor vasculature and some tumor cells (e.g. HT1080). It was reported that NGR-modified stealth liposomes (NGR-SL) could be prepared with different lipid composition, such as 1,2-dipalmitoyl-sn glycero-phosphatidylcholine (DPPC), hydrogenated soy posphatidylcholine (HSPC) and soy posphatidylcholine (SPC). In the present study, NGR-modified liposomes were prepared with DPPC, HSPC, SPC or the mixture of HSPC and SPC. The resultant liposomes with different lipid composition were compared in terms of cell uptake, antitumor efficacy and targeted drug delivery efficiency using HT1080 tumor model. It was found that NGR-SL composed of the mixture of HSPC and SPC was able to improve targeted drug delivery efficiency to tumor producing the most significant antitumor activity. Collectively, the NGR-modified liposomes composed of the mixture of HSPC and SPC are promising carriers for the treatment of tumor. Besides NGR ligand, lipid composition could also significantly affect the targeted delivery efficiency to the tumor. PMID- 26373705 TI - Daily laxative therapy reduces organ dysfunction in mechanically ventilated patients: a phase II randomized controlled trial. AB - INTRODUCTION: Constipation is a common problem in intensive care units. We assessed the efficacy and safety of laxative therapy aiming to promote daily defecation in reducing organ dysfunction in mechanically ventilated patients. METHODS: We conducted a prospective, randomized, controlled, nonblinded phase II clinical trial at two general intensive care units. Patients expected to remain ventilated for over 3 days were randomly assigned to daily defecation or control groups. The intervention group received lactulose and enemas to produce 1-2 defecations per day. In the control group, absence of defecation was tolerated up to 5 days. Primary outcome was the change in Sequential Organ Failure Assessment (SOFA) score between the date of enrollment and intensive care unit discharge, death or day 14. RESULTS: We included 88 patients. Patients in the treatment group had a higher number of defecations per day (1.3 +/- 0.42 versus 0.7 +/- 0.56, p < 0.0001) and lower percentage of days without defecation (33.1 +/- 15.7% versus 62.3 +/- 24.5%, p < 0.0001). Patients in the intervention group had a greater reduction in SOFA score (-4.0 (-6.0 to 0) versus -1.0 (-4.0 to 1.0), p = 0.036) with no difference in mortality rates or in survival time. Adverse events were more frequent in the treatment group (4.5 (3.0-8.0) versus 3.0 (1.0-5.7), p = 0.016), including more days with diarrhea (2.0 (1.0-4.0) versus 1.0 (0-2.0) days, p < 0.0001). Serious adverse events were rare and did not significantly differ between groups. CONCLUSIONS: Laxative therapy improved daily defecation in ventilated patients and was associated with a greater reduction in SOFA score. TRIAL REGISTRATION: Clinical Trials.gov NCT01607060, registered 24 May 2012. PMID- 26373706 TI - Study of association of CTLA4 gene variants to non-anterior uveitis. AB - This study was undertaken to investigate the possible genetic association of functional CTLA4 polymorphisms with susceptibility to non-anterior uveitis. Four hundred and seventeen patients with endogenous non-anterior uveitis and 1517 healthy controls of Spanish Caucasian origin were genotyped for the CTLA4 polymorphisms rs733618, rs5742909 and rs231775, using predesigned TaqMan((c)) allele discrimination assays. PLINK software was used for the statistical analyses. No significant associations between the CTLA4 polymorphisms and susceptibility to global non-anterior uveitis were found. It was also the case when the potential association of these genetic variants with the anatomical localization of the disease, such as intermediate, posterior or panuveitis, was assessed. Our results do not support a relevant role of these CTLA4 polymorphisms in the non-anterior uveitis genetic predisposition. PMID- 26373707 TI - Targeting stem cell niche can protect hematopoietic stem cells from chemotherapy and G-CSF treatment. AB - INTRODUCTION: Hematopoietic stem/progenitor cells (HSPCs) reside in a tightly controlled local microenvironment called bone marrow niche. The specialized microenvironment or niche not only provides a favorable habitat for HSPC maintenance and development but also governs stem cell function. METHOD: We investigated the effect of cytotoxic drugs on bone marrow niche. To mimic the multiple rounds of chemotherapy followed by autologous hematopoietic stem cells (HSCs) transplantation in a clinical setting, we further verified the hypothesis that targeting the niche might improve stem cell-based therapies in mouse models. RESULTS: We found that multiple rounds of cytotoxic drug treatment significantly disrupted niche and serum osteocalcin level was significantly reduced after treatment in autologous HSPCs transplanted patients (P = 0.01). In mouse models, the number of CD45(-)Ter119(-)OPN(+) osteoblasts was significantly reduced after multiple rounds of chemotherapies and granulocyte colony stimulating factor (G CSF) treatment (P < 0.01). Parathyroid hormone (PTH) or receptor activator of nuclear factor kappa-B ligand (RANKL) treatment significantly increased the number of HSCs mobilized into peripheral blood (PB) for stem cell harvesting and protected stem cells from repeated exposure to cytotoxic chemotherapy. Treatments with G-CSF and PTH significantly increased the preservation of the HSC pool (P < 0.05). Moreover, recipient mice transplanted with circulation HSPCs that were previously treated with PTH and RANKL showed robust myeloid and lymphatic cell engraftment compared to the mice transplanted with HSCs after chemotherapy or G CSF treatment. CONCLUSION: These data provide new evidence that the niche may be an important target for drug-based stem cell therapy. PMID- 26373708 TI - Psychometric evaluation of a Czech version of the Family Inventory of Needs. AB - OBJECTIVE: Identification of areas that family members consider important and in which they need help and support is one of the main goals of palliative care. Our research aimed to assess the psychometric properties of a Czech version of the Family Inventory of Needs (FIN). METHOD: The group comprised 272 family members of terminally ill cancer patients at the University Hospital in Ostrava. Reliability was assessed by internal consistency (Cronbach's alpha), test-retest reliability, and correlation of both scales and items within the scales (item total correlation). To verify construct validity, exploratory factor analysis and principal component analysis with a varimax rotation were utilized. RESULTS: Using exploratory factor analysis, the following four factors (domains) were extracted: basic information, information on treatment and care, support, and comfort of the patient. Cronbach's alpha for the entire questionnaire was 0.924 on the importance scale and 0.912 for the satisfaction scale; for all domains, a value of alpha greater than 0.7 was ascertained. Test-retest reliability was also higher than 0.7 for all domains. On the satisfaction scale, a moderate correlation was confirmed between unmet needs in the domains basic information, support, and comfort of the patient, and the total score, and in selected quality of-life domains. SIGNIFICANCE OF RESULTS: The results of tests on the psychometric properties of the FIN questionnaire demonstrated at least satisfactory validity and reliability, and confirmed that it can be employed to assess the needs of palliative care patients in the Czech Republic. PMID- 26373709 TI - Expression, prognostic significance and mutational analysis of protein tyrosine phosphatase SHP-1 in chronic myeloid leukemia. AB - The protein tyrosine phosphatase SHP-1 dephosphorylates BCR-ABL1, thereby serving as a potential control mechanism of BCR-ABL1 kinase activity. Pathways regulating SHP-1 expression, which could be exploited in the therapeutics of TKI-resistant chronic myeloid leukemia (CML), remain unknown. Moreover, the questions of whether there is any kind of SHP-1 deregulation in CML, contributing to disease initiation or evolution, as well as the question of prognostic significance of SHP-1, have not been definitively answered. This study shows moderately lower SHP 1 mRNA expression in chronic phase CML patients in comparison to healthy individuals and no change in SHP-1 mRNA levels after successful TKI treatment. Mutational analysis of the aminoterminal and phosphatase domains of SHP-1 in patients did not reveal genetic lesions. This study also found no correlation of SHP-1 expression at diagnosis with response to treatment, although a trend for lower SHP-1 expression was noted in the very small non-responders' group of the 3 month therapeutic milestone. PMID- 26373710 TI - The inhibitory effects of a RANKL-binding peptide on articular and periarticular bone loss in a murine model of collagen-induced arthritis: a bone histomorphometric study. AB - INTRODUCTION: We designed OP3-4 (YCEIEFCYLIR), a cyclic peptide, to mimic the soluble osteoprotegerin (OPG), and was proven to bind to RANKL (receptor activator of NF-kappaB ligand), thereby inhibiting osteoclastogenesis. We recently found that another RANKL binding peptide, W9, could accelerate bone formation by affecting RANKL signaling in osteoblasts. We herein demonstrate the effects of OP3-4 on bone formation and bone loss in a murine model of rheumatoid arthritis. METHODS: Twenty-four seven-week-old male DBA/1J mice were used to generate a murine model of collagen-induced arthritis (CIA). Then, vehicle or OP3 4 (9 mg/kg/day or 18 mg/kg/day) was subcutaneously infused using infusion pumps for three weeks beginning seven days after the second immunization. The arthritis score was assessed, and the mice were sacrificed on day 49. Thereafter, radiographic, histological and biochemical analyses were performed. RESULTS: The OP3-4 treatment did not significantly inhibit the CIA-induced arthritis, but limited bone loss. Micro-CT images and quantitative measurements of the bone mineral density revealed that 18 mg/kg/day OP3-4 prevented the CIA-induced bone loss at both articular and periarticular sites of tibiae. As expected, OP3-4 significantly reduced the CIA-induced serum CTX levels, a marker of bone resorption. Interestingly, the bone histomorphometric analyses using undecalcified sections showed that OP3-4 prevented the CIA-induced reduction of bone formation-related parameters at the periarticular sites. CONCLUSION: The peptide that mimicked OPG prevented inflammatory bone loss by inhibiting bone resorption and stimulating bone formation. It could therefore be a useful template for the development of small molecule drugs for inflammatory bone loss. PMID- 26373712 TI - Empirical evidence of recall bias for primary health care visits. AB - BACKGROUND: While it is common for an economic evaluation of health care to rely on trial participants for self-reported health service utilisation, there is variability in the accuracy of this data due to potential recall bias. The aim of this study was to quantify the level of recall bias in self-reported primary health care general practitioner (GP) visits following inpatient rehabilitation over a 12 month period. METHODS: This report is a secondary analysis from a larger randomised control trial of an economic evaluation of additional Saturday inpatient rehabilitation. Participants were adults who had been discharged into the community following admission to an acute general rehabilitation hospital. Participants were asked to recall primary health care visits, including community GP visits, via a telephone questionnaire which was administered at 6 and 12 months following discharge from inpatient rehabilitation. Participants were asked to recall health service utilisation over each preceding 6 month period. The self reported data were compared to equivalent claims data from the national insurer, over the same period. RESULTS: 751 participants (75% of the full trial) with a mean age of 74 years (SD 13) were included in this analysis. Over the 12 month period following discharge from rehabilitation there was an under-reporting of 14% in self-reported health service utilisation for GP visits compared to national insurer claims data over the same period. From 0 to 6 months following discharge from rehabilitation, there was an over-reporting of self-reported GP visits of 35% and from 7 to 12 months there was an under-reporting of self reported GP visits of 36%, compared to national insurer claims data over the same period. 46% of patients reported the same or one number difference in self reported GP visits between the 0 to 6 and the 7 to 12 month periods. CONCLUSION: Based on these findings we recommend that an economic evaluation alongside a clinical trial for an elderly adult rehabilitation population include a sensitivity analysis that inflates self-reported GP visits by 16% over 12 months. However caution is required when utilising self-reported GP visits as the data may contain periods of both over and under reporting. Where general practitioner visits are expected to vary significantly between intervention and control groups we recommend that administrative data be included in the trial to accurately capture resources for an economic evaluation. PMID- 26373711 TI - Cost effectiveness and budgetary impact of the Boston University approach to Psychiatric Rehabilitation for societal participation in people with severe mental illness: a randomised controlled trial protocol. AB - BACKGROUND: People with Severe Mental Illness (SMI) frequently experience problems with regard to societal participation (i.e. work, education and daily activities outside the home), and require professional support in this area. The Boston University approach to Psychiatric Rehabilitation (BPR) is a comprehensive methodology that can offer this type of support. To date, several Randomised Controlled Trials (RCT's) investigating the effectiveness of BPR have yielded positive outcomes with regard to societal participation. However, information about the cost-effectiveness and budgetary impact of the methodology, which may be important for broader dissemination of the approach, is lacking. BPR may be more cost effective than Care As Usual (CAU) because an increase in participation and independence may reduce the costs to society. Therefore, the aim of this study is to investigate, from a societal perspective, the cost-effectiveness of BPR for people with SMI who wish to increase their societal participation. In addition, the budget impact of implementing BPR in the Dutch healthcare setting will be assessed by means of a budget impact analysis (BIA) after completion of the trial. METHODS: In a multisite RCT, 225 adults (18-64 years of age) with SMI will be randomly allocated to the experimental (BPR) or the control condition (CAU). Additionally, a pilot study will be conducted with a group of 25 patients with severe and enduring eating disorders. All participants will be offered support aimed at personal rehabilitation goals, and will be monitored over a period of a year. Outcomes will be measured at baseline, and at 6 and 12 months after enrolment. Based on trial results, further analyses will be performed to assess cost-effectiveness and the budgetary impact of implementation scenarios. DISCUSSION: The trial results will provide insight into the cost-effectiveness of BPR in supporting people with SMI who would like to increase their level of societal participation. These results can be used to make decisions about further implementation of the method. Also, assessing budgetary impact will facilitate policymaking. The large sample size, geographic coverage and heterogeneity of the study group will ensure reliable generalisation of the study results. TRIAL REGISTRATION: Current Controlled Trials: ISRCTN88987322. Registered 13 May 2014. PMID- 26373713 TI - Evolution of the avian beta-defensin and cathelicidin genes. AB - BACKGROUND: beta-defensins and cathelicidins are two families of cationic antimicrobial peptides (AMPs) with a broad range of antimicrobial activities that are key components of the innate immune system. Due to their important roles in host defense against rapidly evolving pathogens, the two gene families provide an ideal system for studying adaptive gene evolution. In this study we performed phylogenetic and selection analyses on beta-defensins and cathelicidins from 53 avian species representing 32 orders to examine the evolutionary dynamics of these peptides in birds. RESULTS AND CONCLUSIONS: Avian beta-defensins are found in a gene cluster consisting of 13 subfamiles. Nine of these are conserved as one to one orthologs in all birds, while the others (AvBD1, AvBD3, AvBD7 and AvBD14) are more subject to gene duplication or pseudogenisation events in specific avian lineages. Avian cathelicidins are found in a gene cluster consisting of three subfamilies with species-specific duplications and gene loss. Evidence suggested that the propiece and mature peptide domains of avian cathelicidins are possibly co-evolving in such a way that the cationicity of the mature peptide is partially neutralised by the negative charge of the propiece prior to peptide secretion (further evidence obtained by repeating the analyses on primate cathelicidins). Negative selection (overall mean dN < dS) was detected in most of the gene domains examined, conserving certain amino acid residues that may be functionally crucial for the avian beta-defensins and cathelicidins, while episodic positive selection was also involved in driving the diversification of specific codon sites of certain AMPs in avian evolutionary history. These findings have greatly improved our understanding of the molecular evolution of avian AMPs and will be useful to understand their role in the avian innate immune response. Additionally, the large dataset of beta-defensin and cathelicidin peptides may also provide a valuable resource for translational research and development of novel antimicrobial agents in the future. PMID- 26373715 TI - Persistent GP130/STAT3 Signaling Contributes to the Resistance of Doxorubicin, Cisplatin, and MEK Inhibitor in Human Rhabdomyosarcoma Cells. AB - To test the role of STAT3 in human rhabdomyosarcoma cells, genetic approaches were used to either knockdown the expression of STAT3 and GP130, an upstream activator of STAT3 using short hairpin RNA (shRNA) or express persistently active STAT3 protein. Knockdown expression of GP130 or STAT3 sensitized cells to anti cancer drugs doxorubicin, cisplatin, and MEK inhibitor AZD6244. On the other hand, expression of the constitutively active STAT3 protein reduced the sensitivity of rhabdomyosarcoma cells to those drugs. In addition, we tested a small molecule STAT3 inhibitor LY5 and a GP130 inhibitor bazedoxifene in rhabdomyosarcoma cells. Our data demonstrated that the combination of LY5 or bazedoxifene with doxorubicin, cisplatin, and AZD6244 showed stronger inhibitory effects than single agent alone. In summary, our results demonstrated that GP130/STAT3 signaling contributes to the resistance of these drugs in rhabdomyosarcoma cells. They also suggested a potentially novel cancer therapeutic strategy using the combination of inhibitors of GP130/STAT3 signaling with doxorubicin, cisplatin, or AZD6244 for rhabdomyosarcoma treatments. PMID- 26373714 TI - Use of fluoroquinolones is the single most important risk factor for the high bacterial load in patients with nasal and gastrointestinal colonization by multidrug-resistant Acinetobacter baumannii. AB - Gastrointestinal colonization by carbapenem-resistant Acinetobacter baumannii (CRAB) and multidrug-resistant Acinetobacter baumannii (MRAB) provides an important reservoir for clinical infections and hospital outbreaks. We conducted a 7-month study in a 3200-bed healthcare network to investigate the prevalence of gastrointestinal colonization of CRAB and MRAB in Hong Kong. Between 1 June and 31 December 2014, a total of 17,760 fecal specimens from 9469 patients were screened. Testing showed that 340 (1.9%) specimens from 224 (2.6%) patients were CRAB-positive, which included 70 (0.39%) MRAB-positive specimens from 54 (0.57%) patients. The presence of wound or ulcer, use of broad-spectrum antibiotics in the preceding 6 months, and residence in elderly homes are independent risk factors for gastrointestinal colonization of CRAB. Quantitative bacterial counts in various body sites (rectal, nasal, axilla, wound, catheterized urine, if available) were performed in 33 (61.1%) of 54 MRAB patients. Ten (30.3%) and 8 (24.2%) patients had high bacterial load (defined as over 3 log10) in rectal and nasal swabs, with a median of 5.04 log10 cfu/ml of rectal swab and 4.89 log10 cfu/ml of nasal swab in saline diluent, respectively. Nine (81.8%) of 11 patients with wounds had high bacterial load in wound swabs, with a median of 5.62 log10 cfu/ml. Use of fluoroquinolones 6 months before admission was the only significant factor associated with high bacterial load in nasal and rectal swabs. With the implementation of directly observed hand hygiene before meals and medications to all conscious hospitalized patients, no hospital outbreaks were observed during our study period. PMID- 26373716 TI - Molecular Genetics and Targeted Therapy in Hepatocellular Carcinoma. AB - Hepatocellular carcinoma (HCC) is a highly lethal disease, therefore effective and tolerable treatment is urgently needed. In this article, we provide an updated review of the genetic abnormalities and mechanisms that drive carcinogenesis of HCC, and discuss the targeted therapeutics that are being investigated in HCC. Hepatocellular carcinogenesis typically begins with chronic inflammation of hepatocytes that progressively transform into invasive carcinoma. These events are associated with molecular abnormalities and chromosomal alterations. Multiple analyses of HCC have revealed aberrant expression or activity of growth factors and receptors, and the associated signaling pathways. These molecular alterations are implicated in the development and progression of HCC, and they have been exploited as targets for therapy. Targeted agents that inhibit receptor tyrosine kinases and their downstream signal mediators, angiogenesis, and immunomodulators have been developed and clinically investigated. Among these targeted agents, the multi-kinase inhibitor sorafenib has become the standard treatment for advanced HCC, though its therapeutic benefit is limited. Continued research is essential for improving treatment response and minimizing toxicity for patients with HCC. Future investigation will need to focus on utilizing patterns of gene expression to classify HCC into groups that display similar prognosis and treatment sensitivity, and combining targeted therapeutics with conventional chemotherapy that produce enhanced anti tumor effect. By integration of tumor profiling and targeted therapeutics in HCC, we hope to advance towards the goal of precision treatment for patients with this malignant disease. PMID- 26373717 TI - MYC as Therapeutic Target for Embryonal Tumors: Potential and Challenges. AB - The MYC family plays essential roles during brain development and their oncogenic deregulation is implicated in the formation of embryonal neural tumors such as medulloblastomas (MB) and neuroblastoma (NB). Amplification of the MYCN is the predominant marker for aggressive NB and correlates with poor prognosis, while c MYC overexpression is a defining feature of MB subgroups inflected with aggressive biological behavior and increased likelihood of metastasis. Not surprisingly MYC has emerged as an attractive target for pediatric neural cancer therapy. However despite three decades of intensive research in MYC biology and an impressive number of 30,000 publications, inhibition of MYC as therapeutic strategy remains an elusive goal in cancer medicine. This review discusses the potential and challenges of targeting the oncogenic effects of MYC as therapeutic strategy for MYC over-expressing embryonal neural tumors where current therapies are inadequate. PMID- 26373718 TI - Defining Nano, Nanotechnology and Nanomedicine: Why Should It Matter? AB - Nanotechnology, which involves manipulation of matter on a 'nano' scale, is considered to be a key enabling technology. Medical applications of nanotechnology (commonly known as nanomedicine) are expected to significantly improve disease diagnostic and therapeutic modalities and subsequently reduce health care costs. However, there is no consensus on the definition of nanotechnology or nanomedicine, and this stems from the underlying debate on defining 'nano'. This paper aims to present the diversity in the definition of nanomedicine and its impact on the translation of basic science research in nanotechnology into clinical applications. We present the insights obtained from exploratory qualitative interviews with 46 stakeholders involved in translational nanomedicine from Europe and North America. The definition of nanomedicine has implications for many aspects of translational research including: fund allocation, patents, drug regulatory review processes and approvals, ethical review processes, clinical trials and public acceptance. Given the interdisciplinary nature of the field and common interest in developing effective clinical applications, it is important to have honest and transparent communication about nanomedicine, its benefits and potential harm. A clear and consistent definition of nanomedicine would significantly facilitate trust among various stakeholders including the general public while minimizing the risk of miscommunication and undue fear of nanotechnology and nanomedicine. PMID- 26373719 TI - Changes in the Social Responsibility Attitudes of Engineering Students Over Time. AB - This research explored how engineering student views of their responsibility toward helping individuals and society through their profession, so-called social responsibility, change over time. A survey instrument was administered to students initially primarily in their first year, senior year, or graduate studies majoring in mechanical, civil, or environmental engineering at five institutions in September 2012, April 2013, and March 2014. The majority of the students (57 %) did not change significantly in their social responsibility attitudes, but 23 % decreased and 20 % increased. The students who increased, decreased, or remained the same in their social responsibility attitudes over time did not differ significantly in terms of gender, academic rank, or major. Some differences were found between institutions. Students who decreased in social responsibility initially possessed more positive social responsibility attitudes, were less likely to indicate that college courses impacted their views of social responsibility, and were more likely to have decreased in the frequency that they participated in volunteer activities, compared to students who did not change or increased their social responsibility. Although the large percentage of engineering students who decreased their social responsibility during college was disappointing, it is encouraging that courses and participation in volunteer activities may combat this trend. PMID- 26373720 TI - Inflection and Reflection: Design Issues that Shape the Field of Prevention Science. PMID- 26373722 TI - Erratum to: Development and validation of an ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for the quantitative determination of rhamnolipid congeners. PMID- 26373721 TI - Interval training in the boundaries of severe domain: effects on aerobic parameters. AB - PURPOSE: Although time spent at VO2max (t@VO2max) has been suggested as an optimal stimulus for the promotion of greater VO2max improvements, scientific findings supporting this notion are surprisingly still lacking. To investigate this, the present study described t@VO2max in two different severe-intensity interval training regimens and compared its effects on aerobic indexes after a 4 week intervention. METHODS: Twenty-one recreational cyclists performed an incremental exercise test and six time-to-exhaustion tests on four different days to determine VO2max, lactate threshold (LT), critical power (CP) and the highest intensity (IHIGH) and lowest exercise duration (TLOW) at which VO2max was attained. Subjects were assigned to the lower (LO, n = 11, 4 * 5 min at 105% CP, 1 min recovery) or the upper severe-intensity training groups (UP, n = 10, 8 * 60% TLOW at 100% IHIGH, 1:2 work:recovery ratio). t@VO2max was measured during the first and last training sessions. RESULTS: A significantly higher t@VO2max was elicited in the UP during training sessions in comparison with the LO group (P < 0.05), and superior improvements were observed in VO2max (change in measure +/- 95% confidence interval) (6.3 +/- 1.9 vs. 3.3 +/- 1.8%, P = 0.034 for interaction terms) and LT (54.8 +/- 11.8 vs. 27.9 +/- 11.3%, P = 0.023 for interaction terms). The other aerobic indexes were similarly improved between the groups. CONCLUSION: The present results demonstrated that UP training produced superior gains in VO2max and LT in comparison with LO training, which may be associated with the higher t@VO2max. PMID- 26373723 TI - APC targeting enhances immunogenicity of a novel multistage Fc-fusion tuberculosis vaccine in mice. AB - Numerous studies have demonstrated that targeting immunogens to FcgammaR on antigen-presenting cells (APCs) can selectively uptake and increase cellular immunity in vitro and in vivo. Therefore, the present study was conducted to evaluate immunogenicity of a novel multistage tuberculosis vaccine, a combination of an early and a dormant immunogenic protein, ESAT6 and HspX, fused to Fcgamma2a fragment of mouse IgG2a to target all forms of tuberculosis. Codon-optimized genes consisting of ESAT6, a linker, and HspX fused either to mouse Fcgamma2a (ESAT6:HspX:mFcgamma2a) or 6* His-tag (ESAT6:HspX:His) were synthesized. The resulting proteins were then produced in Pichia pastoris. The fusion proteins were separately emulsified in dimethyldioctadecylammonium bromide(DDA)-trehalose 6,6-dibehenate(TDB) adjuvant, and their immunogenicity with and without bacille Calmette-Guerin (BCG) was assessed in C57BL/6 mice. Th1, Th2, Th17, and T-reg cytokine patterns were evaluated using the ELISA method. Both multistage vaccines induced very strong IL-12 and IFN-gamma secretion from splenic cells; the Fc tagged subunit vaccine induced a more effective Th1 immune response (IFN-gamma, 910 pg/mL, and IL-12, 854 pg/mL) with a very low increase in IL-17 (~0.1 pg/mL) and IL-4 (37 pg/mL) and a mild increase in TGF-beta (543 pg/mL) compared to the BCG or ESAT6:HspX:His primed and boosted groups. The production of IFN-gamma to ESAT6:HspX:Fcgamma2a was very consistent and showed an increasing trend for IL-12 compared to the BCG or ESAT6:HspX:His primed and boosted groups. Fcgamma2a used as a delivery vehicle supported the idea of selective uptake, inducing cross presentation and forming a proper anti-tuberculosis response in context of Th1/Th2 and Th17/T-reg balances, which is important for protection and prevention of damage. PMID- 26373724 TI - Enhancing the vitamin B12 production and growth of Propionibacterium freudenreichii in tofu wastewater via a light-induced vitamin B12 riboswitch. AB - The vitamin B12-dependent riboswitch is a crucial factor that regulates gene transcription to mediate the growth of and vitamin B12 synthesis by Propionibacterium freudenreichii. In this study, the effect of various wavelengths of light on the growth rate and vitamin B12 synthesis was studied. Red, green, and blue light-emitting diodes (LEDs) were selected, and a dark condition was used as the control. The microorganism growth rate was measured using a spectrophotometer and plate counting, while the vitamin B12 content was determined using an HPLC-based method. The optical density at 600 nm (OD600) values indicated that P. freudenreichii grew better under the continuous and discontinuous blue light conditions. Moreover, under the blue light condition, P. freudenreichii tended to have a higher growth rate (0.332 h(-1)) and vitamin B12 synthesis (ca. 10 MUg/mL) in tofu wastewater than in dark conditions. HPLC analysis also showed that more methylcobalamin was produced under the blue light conditions than in the other conditions. The cbiB gene transcription results showed that blue light induced the synthesis of this vitamin B12 synthesis enzyme. Moreover, the results of inhibiting the expression of green fluorescent protein indicated that blue light removed the inhibition by the vitamin B12 dependent riboswitch. This method can be used to reduce fermentation time and produce more vitamin B12 in tofu wastewater. PMID- 26373725 TI - Distinctive non-methanogen archaeal populations in anaerobic digestion. AB - Methanogens define the archaeal communities involved in anaerobic digestion. Recently, non-methanogen archaeal populations have been unexpectedly identified in anaerobic digestion processes. To gain insight into the ecophysiology of these uncharacterized archaeal populations, for the first time, a phylogenetic analysis was performed on a collection of non-methanogen archaeal 16S rRNA gene sequences from anaerobic digesters of broad geographic distribution, revealing a distinct clade formed by these sequences in subgroup 6 of the Miscellaneous Crenarchaeotal Group in the newly proposed archaeal phylum Bathyarchaeota. This exclusive phylogenetic assemblage enabled the development of a real-time quantitative PCR (qPCR) assay specifically targeting these non-methanogen archaeal populations in anaerobic digestion. Application of the qPCR assay in continuous anaerobic digesters indicated that these archaeal populations were minor constituents of the archaeal communities, and the abundance of these populations remained relatively constant irrespective of process perturbations. Analysis of the archaeal populations in methanogenic communities further revealed the co occurrence of these non-methanogen archaea with acetoclastic methanogens. Nevertheless, the low abundance of non-methanogen archaea as compared with acetoclastic methanogens suggests that the non-methanogen archaeal populations were not major players in animal waste-fed methanogenic processes investigated in this study and the functions of these archaeal populations remain to be identified. PMID- 26373727 TI - Lost signature: progress and failures in in vivo tracking of implanted stem cells. AB - Stem cell therapy as a part of regenerative medicine provides promising approaches for the treatment of injuries and diseases. The increasing use of mesenchymal stem cells in various medical treatments created the demand for long term in vivo cell tracking methods. Therefore, it is necessary to analyze post transplantational survival, biodistribution, and engraftment of cells. Furthermore, stem cell treatment has been discussed controversially due to possible association with tumor formation in the recipient. For therapeutic purpose, stem cells must undergo substantial manipulation such as differentiation and in vitro expansion, and this can lead to the occurrence of genetic aberrations and altered expression of both tumor suppression and carcinogenic factors. To control therapy, it is necessary to find a reliable and general method to track and identify implanted cells in the recipient. This is especially challenging for autologous transplantations, as standard fingerprinting methods cannot be applied. An optimal technique for in vivo cell monitoring does not yet exist, and its development holds several challenges: small numbers of transplanted cells, possibility of cell number quantification, minimal transfer of the contrast agent to non-transplanted cells, and no genetic modification. This review discusses most of the proposed solutions, including magnetic resonance imaging, magnetic particle imaging, positron emission tomography, single-photon emission computed tomography, and optical imaging methods. Additionally, the recent research on cell labeling for stem cell monitoring after transplantation including in vitro, ex vivo, and in vivo imaging studies is described. Promising future imaging modalities for stem cell monitoring after transplantation are shown. PMID- 26373728 TI - Properties and biotechnological applications of natural and engineered haloalkane dehalogenases. AB - Haloalkane dehalogenases (HLDs) convert halogenated compounds to corresponding alcohols, halides, and protons. They belong to alpha/beta-hydrolases, and their principal catalytic mechanism is SN2 nucleophilic substitution followed by the addition of water. Since HLDs generally have broad and different substrate specificities, they have various biotechnological applications. HLDs have previously been believed to be present only in bacterial strains that utilize xenobiotic halogenated compounds, and three archetypal HLDs, i.e., DhlA, DhaA, and LinB, have been intensively investigated by biochemical, structural, and computational analyses. Furthermore, by using the resulting data and target selected random mutagenesis approaches, these HLDs have been successfully engineered to improve their substrate specificities and activities. In addition, important insights into protein evolution have been obtained by studying these HLDs. At the same time, the genome and metagenome information has revealed that HLD homologues are widely distributed in many bacterial strains, including ones that have not been reported to degrade halogenated compounds. Some of these cryptic HLD homologues have been experimentally confirmed to be "true" HLDs with unique substrate specificities and enantioselectivities. Although their biological functions and physiological roles remain mysterious, these potential HLDs are considered promising materials for the development of new biocatalysts. PMID- 26373726 TI - Metabolic engineering of Bacillus subtilis for terpenoid production. AB - Terpenoids are the largest group of small-molecule natural products, with more than 60,000 compounds made from isopentenyl diphosphate (IPP) and its isomer dimethylallyl diphosphate (DMAPP). As the most diverse group of small-molecule natural products, terpenoids play an important role in the pharmaceutical, food, and cosmetic industries. For decades, Escherichia coli (E. coli) and Saccharomyces cerevisiae (S. cerevisiae) were extensively studied to biosynthesize terpenoids, because they are both fully amenable to genetic modifications and have vast molecular resources. On the other hand, our literature survey (20 years) revealed that terpenoids are naturally more widespread in Bacillales. In the mid-1990s, an inherent methylerythritol phosphate (MEP) pathway was discovered in Bacillus subtilis (B. subtilis). Since B. subtilis is a generally recognized as safe (GRAS) organism and has long been used for the industrial production of proteins, attempts to biosynthesize terpenoids in this bacterium have aroused much interest in the scientific community. This review discusses metabolic engineering of B. subtilis for terpenoid production, and encountered challenges will be discussed. We will summarize some major advances and outline future directions for exploiting the potential of B. subtilis as a desired "cell factory" to produce terpenoids. PMID- 26373729 TI - Functional evaluation in orthodontic surgical treatment: long-term stability and predictability. AB - BACKGROUND: The introduction of electromyographic and kinesiographic technology in orthodontics allows to obtain objective data regarding the functional aspects of the mandibular movements and the masticatory muscular activity. It is then important to be able to correlate the data obtained by instrumental activity with the clinical ones. The aim of this study consists to analyse the post ortodontic surgical stability through instrumental evaluation of the masticatory muscles and mandibular movements. METHOD: 30 patients undergo electromyographic and kinesiographic evaluations through all the surgical orthodontic iter and were than followed during other 4 years. JMP software was used to analyze and correlate the electromyographic and knesioographic data during treatment and during the follow up. RESULTS: A linear correlations between some functional objective values collected from the examinations at the beginning and during therapy and the follow up one has been demonstrated. CONCLUSION: It is important to submit patients in surgical ortodontic treatment to instrumental analysis which can evidence how masticatory function and mandibular movements are performed. It is also important to highlight some functional values also from the beginning of the treatment because an alteration of such values can be related to a better or worse postsurgical rehabilitation. PMID- 26373730 TI - Failure rates of mini-implants placed in the infrazygomatic region. AB - BACKGROUND: The purpose of this pilot study was to evaluate the failure rates of mini-implants placed in the infrazygomatic region and to evaluate factors that affect their stability. METHODS: A retrospective cohort study of 30 consecutive patients (55 mini-implants) who had infrazygomatic mini-implants at a University Clinic were evaluated for failure rates. Patient, mini-implant, orthodontic, surgical, and mini-implant maintenance factors were evaluated by univariate logistic regression models for association to failure rates. RESULTS: A 21.8 % failure rate of mini-implants placed in the infazygomatic region was observed. None of the predictor variables were significantly associated with higher or lower odds for failed implants. CONCLUSIONS: Failure rates for infrazygomatic mini-implants were slightly higher than those reported in other maxilla mandibular osseous locations. No predictor variables were found to be associated to the failure rates. PMID- 26373731 TI - Overexpression of 3-phosphoinositide-dependent protein kinase-1 is associated with prognosis of gastric carcinoma. AB - This study investigated the correlation between the expression of 3 phosphoinositide-dependent protein kinase-1 (PDK1) and the prognosis of gastric carcinoma patients. A total of 156 paired tumor and matched normal samples were collected from patients of gastric carcinoma who underwent surgical resection. The expression of PDK1 was analyzed by real-time quantitative PCR and immunohistochemistry method. Potential correlation between PDK1 protein expression and the clinicopathological characteristics was determined by chi square test and Spearman correlation analysis. The influence of PDK1 expression on 5-year survival rate and survival length was determined by Kaplan-Meier analysis. The expression of PDK1 mRNA and protein were significantly higher in tumor samples comparing to those in adjacent normal samples (paired t test, P = 0.007). Immunohistochemical staining results indicated that PDK1 protein level was positively correlated with infiltration (P = 0.006). However, no associations with age, sex, clinical stage, lymph node metastasis, and distant metastasis were observed (P > 0.05). The 5-year survival rate was 20.1 and 63.4 % of the patients with high and low expression level of PDK1, respectively (P < 0.05). The median survival length was 32.5 months (95 % CI 22.8-37.6) for patients with high level of PDK1 and 63.1 months (95 % CI 52.3-64.7) for patients with low level of PDK1 (*2 = 20.153, P < 0.05). Kaplan-Meier survival curves demonstrated that elevated expression of PDK1 was an independent negative prognostic factor of gastric carcinoma (P<0.05). Our study indicated that PDK1 might serve as a candidate pro oncogene and a potential prognostic biomarker for gastric carcinoma. PMID- 26373732 TI - Peritoneal sarcomatosis: site of origin for the establishment of an in vitro and in vivo cell line model to study therapeutic resistance in dedifferentiated liposarcoma. AB - Approximately 50-70 % of patients with retroperitoneal or intraabdominal sarcoma develop a relapse after surgical therapy, including peritoneal sarcomatosis, an extremely rare site of metastatic disease which is associated with an extremely poor prognosis. Accordingly, the establishment of a permanent cell line derived from peritoneal sarcomatosis might provide a helpful tool to understand the biological behavior and to develop new therapeutic strategies. Thus, we established and characterized a liposarcoma cell line (Lipo-DUE1) from a peritoneal sarcomatosis that was permanently cultured without showing any morphological changes. Lipo-DUE1 cells exhibited a spindle-shaped morphology and positive staining for S100. Tumorigenicity was demonstrated in vitro by invasion and migration assays and in vivo by using a subcutaneous xenograft mouse model. In addition, aCGH analysis revealed concordant copy number variations on chromosome 12q in the primary tumor, peritoneal sarcomatosis, and Lipo-DUE1 cells that are commonly observed in liposarcoma. Chemotherapeutic sensitivity assays revealed a pronounced drug-resistant phenotype of Lipo-DUE1 cells to conventionally used chemotherapeutic agents. In conclusion, we describe for the first time the establishment and characterization of a liposarcoma cell line derived from a peritoneal sarcomatosis. Hence, in the future, the newly established cell line Lipo-DUE1 might serve as a useful in vitro and in vivo model to investigate the biological behavior of liposarcoma and to assess novel targeted therapies. PMID- 26373733 TI - Tubb3 regulation by the Erk and Akt signaling pathways: a mechanism involved in the effect of arginine ADP-ribosyltransferase 1 (Art1) on apoptosis of colon carcinoma CT26 cells. AB - The influence of the most important classical mono-ADP-ribosyltransferase, arginine ADP-ribosyltransferase 1 (Art1), on survival and apoptosis of colon carcinoma cells and the potential mechanisms have been partly discussed in our previous study but still need to be further studied. In this present study, Art1 of colon carcinoma CT26 cells was silenced with lentiviral vector-mediated short hairpin RNA (shRNA) or overexpressed with lentiviral vector-mediated complementary DNA (cDNA) and allograft transplant tumors are established in Balb/c mice. We verified Art1 knockdown increases apoptosis of CT26 cells transplant tumor; Art1 overexpression acts oppositely. Accordingly, growth of transplant tumors is inhibited in Art1 knockdown transplant tumors and increases in Art1 overexpression transplant tumors. Furthermore, activity of Akt and Erk cell signal pathways and expression of an apoptosis biomarker, betaIII-tubulin (Tubb3), decrease when Art1 was silenced and increase when Art1 was overexpressed. Inhibiting Akt pathway or Erk pathway both downregulates expression of Tubb3 on protein and messenger RNA (mRNA) level, indicating that Tubb3 could be regulated by both Akt and Erk pathways, and plays a role in the influence of Art1 on apoptosis of Balb/c mice allograft transplant tumor. We also demonstrated that Bcl-2 family is not the responsible downstream factor of the Erk pathway in colon carcinoma cells which is undergoing apoptosis. These findings enrich the molecular mechanism for the function of Art1 in colon carcinoma and provide a complementary support for Art1 to be a potential therapeutic target of the treatment of this kind of malignant tumor. PMID- 26373734 TI - A molecular and biophysical comparison of macromolecular changes in imatinib sensitive and imatinib-resistant K562 cells exposed to ponatinib. AB - Chronic myeloid leukemia (CML) is a type of hematological malignancy that is characterized by the generation of Philadelphia chromosome encoding BCR/ABL oncoprotein. Tyrosine kinase inhibitors (TKIs), imatinib, nilotinib, and dasatinib, are used for the frontline therapy of CML. Development of resistance against these TKIs in the patients bearing T315I mutation is a major obstacle in CML therapy. Ponatinib, the third-generation TKI, is novel drug that is effective even in CML patients with T315I mutation. The exact mechanism of ponatinib in CML has been still unknown. In this study, we aimed to determine the potential mechanisms and structural metabolic changes activated by ponatinib treatment in imatinib-sensitive K562 human CML cell lines and 3 MUM-imatinib-resistant K562/IMA3 CML cell lines generated at our lab. Apoptotic and antiproliferative effects of ponatinib on imatinib-sensitive and 3 MUM-imatinib-resistant K562/IMA3 CML cells were determined by proliferation and apoptosis assays. Additionally, the effects of ponatinib on macromolecules and lipid profiles were also analyzed using Fourier transform infrared spectroscopy (FTIR). Our results revealed that ponatinib inhibited cell proliferation and induced apoptosis as determined by loss of mitochondrial membrane potential, increased caspase-3 enzyme activity, and transfer of phosphatidylserine to the plasma membrane in both K562 and K562/IMA-3 cells. Furthermore, cell cycle analyses revealed that ponatinib arrested K562 and K562/IMA-3 cells at G1 phase. Moreover, ponatinib treatment created a more ordered nucleic acid structure in the resistant cells. Although the lipid to protein ratio increased in imatinib-sensitive K562 cells with a little decrease in the K562/IMA-3 cells, ponatinib treatment indicated significant changes in the lipid composition such as a significant increase in the cellular cholesterol amounts much more in the K562/IMA-3 cells than the sensitive counterparts. Unsaturation in lipids was higher in the resistant cells; however, increases in lipids without phosphate and the number of acyl chains were much higher in the K562 cells. Taken together, all these results showed powerful antiproliferative and apoptotic effects of ponatinib in both imatinib-sensitive and imatinib-resistant CML cells in a dose-dependent manner, and hence, the use of ponatinib for the treatment of TKI-resistant CML patients may be an effective treatment approach in the clinic. More importantly, these results showed that FTIR spectroscopy can detect drug-induced physiological changes in cancer drug resistance. PMID- 26373736 TI - The 42nd Congress of the International Society of Oncology and Biomarkers "ONCOLOGY IN THE BIOMARKER ERA: Biology-Diagnostics-Therapy" ISOBM 2015 : October 3-7, 2015, Hotel Belvedere, Zakopane, POLAND. PMID- 26373735 TI - SNHG3 correlates with malignant status and poor prognosis in hepatocellular carcinoma. AB - Long noncoding RNAs (lncRNAs) have been found dysregulated in human disease, especially in cancer. Small nucleolar RNA host gene 3 (SNHG3) is an lncRNA whose potential function and mechanism in hepatocellular carcinoma (HCC) remain largely unknown. In the present study, we aimed to determine SNHG3 expression and its clinical significance in HCC. Our results showed that the expression level of SNHG3 was significantly upregulated in HCC tissues compared with paired noncancerous tissues from 51 HCC patients, as determined by quantitative real time polymerase chain reaction (qRT-PCR; P < 0.001), which was consistent with the results of two independent HCC cohorts from The Cancer Genome Atlas (TCGA) and Oncomine databases (P < 0.0001 and P = 0.0325, respectively). These results were further confirmed in 144 paired paraffin-embedded HCC specimens by in situ hybridization assay (ISH). Furthermore, SNHG3 expression was significantly correlated with tumor size (P = 0.003), portal vein tumor thrombus (PVTT; P = 0.014), and relapse (P = 0.038). The high expression level of SNHG3 was markedly correlated with overall survival (OS; P < 0.0001), recurrence-free survival (RFS; P = 0.006), and disease-free survival (DFS; P < 0.0001). More importantly, multivariate analysis indicated that SNHG3 expression was an independent prognostic factor for HCC patients (P < 0.001). In conclusion, increased SNHG3 expression is associated with malignant status and poor prognosis in HCC patients. PMID- 26373738 TI - Glucose diffusivity in cell-seeded tissue engineering scaffolds. AB - OBJECTIVE: To determine the effective glucose diffusion coefficient in cell seeded porous scaffolds to understand the importance of nutrient diffusion in tissue engineering bioreactors. RESULTS: Cell growth changed the morphological structure of the scaffolds decreasing the effective pore space and, inevitably, decreasing the effective glucose diffusivity in the chosen scaffolds, namely, collagen, poly(L-lactide) and poly(caprolactone) scaffolds from 3.7 * 10(-9) to 3.2 * 10(-9) m(2)/s, 1.4 * 10(-10) to 9.1 * 10(-11) m(2)/s and 1.8 * 10(-10) to 1.3 * 10(-10) m(2)/s, respectively. CONCLUSIONS: The presence of cells over time during cell culture reduces the mobility of glucose. The results can predict the glucose concentration profiles in thick engineered tissues. PMID- 26373739 TI - Functional characterization of ent-copalyl diphosphate synthase from Andrographis paniculata with putative involvement in andrographolides biosynthesis. AB - OBJECTIVES: To characterize the ent-copalyl diphosphate (ent-CPP) synthase involved in the biosynthetic pathway of andrographolides in a medicinal plant, Andrographis paniculata. RESULTS: The ent-CPP synthase (ent-CPS) gene was cloned from A. paniculata and its encoded ApCPS was demonstrated to react with (E,E,E) geranylgeranyl diphosphate to form ent-CPP through recombinant expression in Escherichia coli. Site-directed mutagenesis of the Asp to Ala in the conserved DXDD motif of ApCPS resulted in loss of function. One Arg is located in the conserved position close to DXDD motif indicating the involvement of ApCPS in specialized metabolism. In addition, RT-PCR analysis revealed that ApCPS was expressed in all tissues of A. paniculata at all growth stages, which is consistent with andrographolides accumulating in these organs. Methyl jasmonate induced ApCPS gene expression, matching inducible accumulation of andrographolides in vivo. CONCLUSIONS: ApCPS is the first ent-CPS characterized in A. paniculata and is suggested to be involved in biosynthesis of andrographolides that have high pharmaceutical values. PMID- 26373740 TI - IL-17A is implicated in lipopolysaccharide-induced neuroinflammation and cognitive impairment in aged rats via microglial activation. AB - BACKGROUND: Neuroinflammation is considered a risk factor for impairments in neuronal function and cognition that arise with trauma, infection, and/or disease. IL-17A has been determined to be involved in neurodegenerative diseases such as multiple sclerosis. Recently, IL-17A has been shown to be upregulated in lipopolysaccharide(LPS)-induced systemic inflammation. This study aims to explore the role of IL-17A in LPS-induced neuroinflammation and cognitive impairment. METHODS: Male Sprague-Dawley (SD) rats were injected intraperitoneally with LPS (500 MUg/kg), and IL-17A expression in serum and in the hippocampus was examined 6, 12, 24, and 48 h later. Then, we investigated whether IL-17A-neutralizing antibodies (IL-17A Abs, 1 mg/kg) prevented neuroinflammation and memory dysfunction in aged rats that received LPS (500 MUg/kg) injection. In addition, the effect of IL-17A on microglial activation in vitro was determined using ELISA and immunofluorescence. RESULTS: LPS injection increased the expression of IL-17A in serum and in the hippocampus. IL-17A Abs improved LPS-induced memory impairment. In addition, IL-17A Abs prevented the LPS-induced expression of TNF alpha, IL-6 and inflammatory proteins, and of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) as well as the activation of microglia in the brain. IL-17A Abs also inhibited the expression of amyloid precursor protein (APP) and BACE1 and increased the expression of the synaptic marker PSD95 in the aged rats treated with LPS. In an in vitro study, we found that recombinant IL 17A could simulate microglial activation and increase production of pro inflammatory cytokines. CONCLUSION: Taken together, our results suggest that IL 17A was involved in LPS-induced neuroinflammation and cognitive impairment in aged rats via microglial activation. Anti-IL-17A may represent a new therapeutic strategy for the treatment of endotoxemia-induced neuroinflammation and cognitive dysfunction. PMID- 26373741 TI - Feasibility, acceptance and long-term exercise behaviour in cancer patients: an exercise intervention by using a swinging-ring system. AB - PURPOSE: Aim of this pilot study was to describe feasibility and acceptance of an exercise intervention by using an unique swinging-ring system with the goal to promote long-term exercise behaviour in cancer patients. METHODS: The included cancer patients (n = 13, male:f emale (m:f) = 7:6, age = 56 +/- 11, range 38-74a) were invited to perform a home-based exercise intervention. All participants of this pilot study were instructed how to use the smovey(r) Vibroswing. They could choose how to use the swinging-ring system, for example only indoor or only outdoor (single or in a group) or both. Feasibility and acceptance were assessed after 12 months (T2). Handgrip strength (Jamar hand dynamometer) and health related quality of life (QOL, SF-36 Health survey) were assessed at baseline (T1) and after 12 months (T2). RESULTS: A total of 10 (77%) patients (m:f = 5:5, 59 +/ 9 years, range = 46-74) could be assessed at baseline and after 12 months. The exercise intervention showed no adverse events and was well accepted. Approximately 77% of patients of the study population have been exercising for more than 12 months. Furthermore, this intervention was able to increase handgrip strength in the participants. QOL improved as well in all domains. CONCLUSIONS: The results of this small pilot study indicate that regular physical exercise with this swinging-ring system seems to be safe, and to promote long-term exercise behaviour of the included patients. Furthermore, this study population showed benefits in terms of increased handgrip strength and of improved QOL. PMID- 26373742 TI - Clinical and laboratory characteristics of viral lower respiratory tract infections in preschool children. AB - BACKGROUND: Viral lower respiratory tract infections are the leading cause of hospitalizations in preschool children. Clinical pictures of different viral causes are not well characterized. The aim of this study was to establish the differences in clinical and laboratory characteristics between the different viral causes of lower respiratory tract infections in preschool children. METHODS: We included 278 preschool children hospitalized because of lower respiratory tract infection. White blood cell count and C-reactive protein values were determined and chest X-ray was performed in most patients. Polymerase chain reaction assay was used for the detection of viral pathogens from nasopharyngeal swab. RESULTS: Pneumonia was present in 71.4 % of all coronavirus infections, 35.1 % of all respiratory syncytial virus infections, and 13.0 % of all rhinovirus infections. Coronavirus (p = 0.03) and respiratory syncytial virus (p < 0.01) were retrospectively shown to be associated with the presence of pneumonia and rhinovirus (p < 0.01) with the absence of pneumonia. Wheezing was present in 81.5 % of all rhinovirus infections and in only 33.3 % of all adenovirus infections. Rhinovirus (p < 0.01) was associated with the presence of wheezing and adenovirus (p = 0.05) with the absence of wheezing. In adenovirus infections mean C-reactive protein value was 72.4 mg/L and white blood cell count 19.000/ul, both significantly higher than in other viruses (p < 0.01). CONCLUSIONS: Clinical and laboratory characteristics of viral lower respiratory tract infections significantly differ. With the advance of viral detection methods and increase of knowledge it becomes possible to characterize different respiratory viral infections and to improve the differential diagnosis. PMID- 26373743 TI - Influence of a combination of probiotics on bacterial infections in very low birthweight newborns. AB - BACKGROUND: Late-onset infections are an important cause of morbidity and mortality in preterm infants. The purpose of our prospective randomised study was to establish whether a combination of probiotics (Lactobacillus acidophilus, Enterococcus faecium and Bifidobacterium infantum) affects the incidence of late onset sepsis and other infections in very low birthweight infants (birthweight under 1500 g, gestational age under 33 weeks). METHODS: From 80 included infants, one half received probiotics (L. acidophilus, E. faecium and B. infantum) in the ratio 1.5:1:1.5, at a dose of 0.6 * 107 colony-forming units twice daily, given with the first portions of milk until discharge, whereas the other half did not. RESULTS: In the group receiving probiotics, 16 children had late-onset sepsis compared with 29 in the group without probiotics; p = 0.006. The number of late onset septic events was lower (30) in the group receiving probiotics than in the group that did not receive probiotics (69); p = 0.003. Furthermore, fewer children had at least one late-onset infection (20 infants in the group receiving probiotics compared with 32 in the group without them; p = 0.009). There were less episodes of late-onset infections in the group receiving probiotics (35) than in the group without probiotics (79); p = 0.002. CONCLUSIONS: A combination of probiotics at a low dose (1.2 * 107 colony-forming units) decreased the frequency of late-onset sepsis and other infections, as described in previous studies. In addition, children were discharged at a lower postmenstrual age. There were no side effects of probiotics reported. PMID- 26373744 TI - Pollen information consumption as an indicator of pollen allergy burden. AB - BACKGROUND: The Austrian pollen information service distributes pollen forecasts and offers various options (webpages, a mobile "Pollen" app, interviews for newspapers, radio, TV and information for the press agency) to support and inform pollen allergy sufferers in Austria in the best way to help to avoid their allergen. These services are well received and user numbers have increased, especially in recent years. METHODS: Herein, we unravel for the first time the user pattern over time on a monthly basis and compare it to the major pollen seasons in Austria as well as to the allergic burden. RESULTS: The symptom load conforms to the web page user numbers and shows the same peaks from the study period of 2012 until 2014. The highest impact in user numbers and allergy burden occurred during the birch pollen season, although similar values were approached during the grass pollen season in 2014. Pollen loads during the respective pollen seasons of birch, grasses and herbs (mugwort and ragweed) mirrored the pattern as well, although to a minor extent, because different plant taxa have a different distribution within Austria and produce different amounts of pollen. CONCLUSION: This study provides evidence that pollen information consumption can be seen as an indicator of the burden of pollen allergy sufferers as well as an indicator of the main flowering periods of the main plants inducing pollen allergies in Austria. PMID- 26373745 TI - Effects of body mass index, mesenteric and abdominal subcutaneous adipose tissue on the spinopelvic parameters. AB - PURPOSE: The purpose of this study was to investigate the effects of body mass index (BMI), thickness of the abdominal subcutaneous adipose tissue (ASAT), thickness of the mesenteric adipose tissue (MAT), weight and height on spinopelvic parameters. METHODS: A total of 400 patients presented to the radiology department for whole abdominal computed tomography were included in the study. Patients' weight and height were measured to calculate BMI. Thickness of ASAT and MAT, lumbosacral angle (LSA), sacral slope (SS), pelvic tilt (PT), and pelvic incidence (PI) were measured from the images obtained. We analyzed the effects of BMI, ASAT, and MAT on spinopelvic parameters. In addition, patients included in the study were screened for isthmic spondylolisthesis and transitional vertebrae. Statistical analysis was carried out using SPSS 15.0 package software. p < 0.05 Values were considered statistically significant. RESULTS: BMI and thickness of ASAT and MAT increased with aging both in male and female individuals. There was a positive correlation between PI and weight, thickness of ASAT and thickness of MAT, while a negative correlation was found between PI and height (p < 0.01). SS angle was positively correlated with weight (p < 0.01). A weak positive correlation was found between PT angle and thickness of MAT and height (p < 0.05). The rate of transitional vertebrae and isthmic spondylolisthesis was 2 and 4.6%, consecutively. PI and SS values were significantly higher in the subjects having spondylolisthesis than normal population (p < 0.01). CONCLUSION: It should be kept in mind that obesity might increase the risk for development of spondylolisthesis by causing increase in PI angle. PMID- 26373746 TI - Rupture of splenic artery aneurysm in primipara five days after cesarean section: case report and review of the literature. AB - Splenic artery aneurysm (SAA) is a rare and usually asymptomatic vascular anomaly which carries the risk of rupture and fatal hemorrhage. It is more common in women and is usually associated with pregnancy. We present the case of rupture of SAA, 5 days after giving birth by cesarean section, which was diagnosed with Multi-Slice Computed Tomografy (MSCT) angiography and was successfully operated in the second emergency laparotomy, with the final good outcome for the mother. This case indicates that in case of sudden bleeding in the abdomen, with the development of hypovolemic shock, especially in the peripartum period, should be suspected rupture of SAA. The paper presents a critical review of this case, with a review of the literature. PMID- 26373747 TI - Rising prevalence of back pain in Austria: considering regional disparities. AB - BACKGROUND: Back pain is the most common form of musculoskeletal conditions and leads to high health care costs. Information about geographic variations in highly prevalent diseases/disorders represents important implications for public health planning to face structural challenges. The present study aims to investigate regional trends in the prevalence of back pain and the role of obesity and social inequalities among Austrian adults. METHODS: A secondary data analysis based on five nationally representative cross-sectional surveys (1973 2007) was carried out (N = 178,818). Back pain was measured as self-reported presence. Obesity (BMI >= 30 kg/m2) was adjusted for self-report bias. For the regional analyses, Austria was divided into Western, Central and Eastern Austria. A relative index of inequality (RII) was computed to quantify the extent of social inequality. RESULTS: A continuous rise in back pain prevalence was observed in the three regions and among all investigated subgroups. In 2007 the age-standardised prevalence was similar in Central (36.9 %), Western (35.2 %) and Eastern Austria (34.3 %). The absolute change in back pain prevalence was highest among obese subjects in Central Austria (women: + 29.8 %, men: + 32.5 %). RIIs were unstable during the study period and in 2007 highest in Eastern Austria. CONCLUSION: Variation and trends in back pain are not attributable to geographic variation in Austria: an assumed East-West gradient in Austria has not been confirmed. Nevertheless our study confirms that back pain dramatically increased in all Austrian regions and investigated subgroups. This worrying trend should be further monitored and public health interventions should be implemented increasingly, especially among obese women and men. PMID- 26373749 TI - Aortic issues in scoliosis and scoliotic operations. AB - The spatial relations between the aorta and vertebrae are changing with posture, surgical techniques, and operative maneuvers. "Risky screws" (within 1-3 mm proximity to the aorta or other adjacent tissues) were found in 5.8-15.2% screws. In order to avoid early and later aortic complications secondary to scoliotic operations, careful preoperative metrology of aorto-vertebrae relations is of crucial importance. Compared with patients with idiopathic scoliosis, Marfan related scoliosis is characterized by faster progression and it is more bracing resistant due to the particular developmental anomalies in Marfan syndrome, implying the refractory nature of the latter. The present study aims to highlight the clinical impact of preoperative aorto-vertebra metrology in the scoliotic operations. PMID- 26373748 TI - Iron metabolism and iron supplementation in cancer patients. AB - Iron deficiency and iron deficiency-associated anemia are common complications in cancer patients. Most iron deficient cancer patients present with functional iron deficiency (FID), a status with adequate storage iron, but insufficient iron supply for erythroblasts and other iron dependent tissues. FID is the consequence of the cancer-associated cytokine release, while in absolute iron deficiency iron stores are depleted resulting in similar but often more severe symptoms of insufficient iron supply. Here we present a short review on the epidemiology, pathophysiology, diagnosis, clinical symptoms, and treatment of iron deficiency in cancer patients. Special emphasis is given to intravenous iron supplementation and on the benefits and limitations of different formulations. Based on these considerations and recommendations from current international guidelines we developed recommendations for clinical practice and classified the level of evidence and grade of recommendation according to the principles of evidence based medicine. PMID- 26373750 TI - Subclinical hypothyroidism and mortality in a large Austrian cohort: a possible impact on treatment? AB - BACKGROUND: Clinical implications of subclinical hypothyroidism (SCH) are still matter of intense debate, resulting in the controversial discussion whether subclinical hypothyroidism should be treated. We performed a cohort study to evaluate the impact of subclinical hypothyroidism on vascular and overall mortality. METHODS: Between 02/1993 and 03/2004, a total of 103,135 persons attending the General Hospital Vienna with baseline serum thyrotropin (TSH, thyroid-stimulating hormone) and free thyroxin (fT4) measurements could be enrolled in a retrospective cohort study. Subclinical hypothyroidism was defined by elevated TSH ranging from 4.5 to 20.0 mIU/L and normal fT4 concentration (0.7 1.7 ng/dL). Overall and vascular mortality as primary endpoints were assessed via record linkage with the Austrian Death Registry. RESULTS: A total of 80,490 subjects fulfilled inclusion criteria of whom 3934 participants (3.7%) were classified as SCH (868 males and 3066 females, median age 48 years). The mean follow-up among the 80,490 subjects was 4.1 years yielding an observation period of 373,301 person-years at risk. In a multivariate Cox regression model adjusted for age and gender TSH levels showed a dose-dependent association with all-cause mortality. The association between SCH and overall or vascular mortality was stronger in men below 60 years compared to older males or females. CONCLUSION: Our data support the hypothesis that SCH might represent an independent risk factor for overall and vascular mortality, especially in men below 60 years. Whether this group would benefit from replacement therapy should be evaluated in interventional studies. PMID- 26373751 TI - Liver metastases from adenocarcinomas of unknown primary site: management and prognosis in 68 consecutive patients. AB - BACKGROUND: In this retrospective study, we aimed to evaluate the clinicopathological characteristics of the patients presenting with liver metastases from unknown primary site besides survival rates, treatment outcomes, and prognostic factors. METHODS: In all, 68 patients followed-up at our center with adenocarcinoma of unknown primary (ACUP) metastatic to the liver between 2005 and 2013 were enrolled. All of the liver metastases were proven by liver biopsy and all yielded diagnosis of adenocarcinoma. RESULTS: Median age was 61 years (29-90) and most of the patients were male (male/female: 43/25). The liver was the only metastatic site in 2 (3%) patients whilst 66 patients (97%) had extrahepatic metastases. The most common extrahepatic metastatic sites were lymph nodes (89.7%), lungs (32.4%), bones (25%), peritoneum (11.8%), brain (4.4%), and adrenal glands (2.9%). Of all 68 patients, 39 (57.4%) were treated with chemotherapy. Median overall survival (OS) was significantly higher in ACUP patients treated with chemotherapy [12.5 months (95% CI 8.3-16.7) vs. 4 months (95% CI 1.2-6.8), (p = 0.026), respectively]. In multivariate analysis, ECOG (Eastern Cooperative Oncology Group) performance status (p = 0.009), chemotherapy (p = 0.024), serum albumin (p = 0.012), and serum CA 19-9 level (p = 0.026) at initial diagnosis were identified as independent prognostic factors influencing survival for the patients with liver metastases from ACUP. CONCLUSION: Patients with liver metastases from ACUP have poor prognosis and chemotherapy improves survival. Decreased serum albumin level, increased CA 19-9 level and poor performance status are independent poor prognostic factors. PMID- 26373752 TI - Impact of an advanced image-based monoenergetic reconstruction algorithm on coronary stent visualization using third generation dual-source dual-energy CT: a phantom study. AB - PURPOSE: To evaluate the impact of an advanced monoenergetic (ME) reconstruction algorithm on CT coronary stent imaging in a phantom model. MATERIALS AND METHODS: Three stents with lumen diameters of 2.25, 3.0 and 3.5 mm were examined with a third-generation dual-source dual-energy CT (DECT). Tube potential was set at 90/Sn150 kV for DE and 70, 90 or 120 kV for single-energy (SE) acquisitions and advanced modelled iterative reconstruction was used. Overall, 23 reconstructions were evaluated for each stent including three SE acquisitions and ten advanced and standard ME images with virtual photon energies from 40 to 130 keV, respectively. In-stent luminal diameter was measured and compared to nominal lumen diameter to determine stent lumen visibility. Contrast-to-noise ratio was calculated. RESULTS: Advanced ME reconstructions substantially increased lumen visibility in comparison to SE for stents <=3 mm. 130 keV images produced the best mean lumen visibility: 86 % for the 2.25 mm stent (82 % for standard ME and 64 % for SE) and 82 % for the 3.0 mm stent (77 % for standard ME and 69 % for SE). Mean DLP for SE 120 kV and DE acquisitions were 114.4 +/- 9.8 and 58.9 +/- 2.2 mGy * cm, respectively. CONCLUSION: DECT with advanced ME reconstructions improves the in-lumen visibility of small stents in comparison with standard ME and SE imaging. KEY POINTS: * An advanced image-based monoenergetic reconstruction algorithm improves lumen visualization in stents <=3.0 mm. * Application of high keV reconstructions significantly improves in-stent lumen visualization. * DECT acquisition resulted in 49 % radiation dose reduction compared with 120 kV SE. PMID- 26373753 TI - Portal hypertension in patients with cirrhosis: indirect assessment of hepatic venous pressure gradient by measuring azygos flow with 2D-cine phase-contrast magnetic resonance imaging. AB - OBJECTIVES: To measure azygos, portal and aortic flow by two-dimensional cine phase-contrast magnetic resonance imaging (2D-cine PC MRI), and to compare the MRI values to hepatic venous pressure gradient (HVPG) measurements, in patients with cirrhosis. METHODS: Sixty-nine patients with cirrhosis were prospectively included. All patients underwent HVPG measurements, upper gastrointestinal endoscopy and 2D-cine PC MRI measurements of azygos, portal and aortic blood flow. Univariate and multivariate regression analyses were used to evaluate the correlation between the blood flow and HVPG. The performance of 2D-cine PC MRI to diagnose severe portal hypertension (HVPG >= 16 mmHg) was determined by receiver operating characteristic curve (ROC) analysis, and area under the curves (AUC) were compared. RESULTS: Azygos and aortic flow values were associated with HVPG in univariate linear regression model. Azygos flow (p < 10(-3)), aortic flow (p = 0.001), age (p = 0.001) and presence of varices (p < 10(-3)) were independently associated with HVPG. Azygos flow (AUC = 0.96 (95 % CI [0.91-1.00]) had significantly higher AUC than aortic (AUC = 0.64 (95 % CI [0.51-0.77]) or portal blood flow (AUC = 0.40 (95 % CI [0.25-0.54]). CONCLUSIONS: 2D-cine PC MRI is a promising technique to evaluate significant portal hypertension in patients with cirrhosis. KEY POINTS: * Noninvasive HVPG assessment can be performed with MRI azygos flow. * Azygos MRI flow is an easy-to-measure marker to detect significant portal hypertension. * MRI flow is more specific that varice grade to detect portal hypertension. PMID- 26373754 TI - Contrast-enhanced dual energy mammography with a novel anode/filter combination and artifact reduction: a feasibility study. AB - OBJECTIVES: To demonstrate the feasibility of contrast-enhanced dual-energy mammography (CEDEM) using titanium (Ti) filtering at 49 kVp for high-energy images and a novel artefact reducing image-subtraction post-processing algorithm. METHODS: Fifteen patients with suspicious findings (ACR BI-RADS 4 and 5) detected with digital mammography (MG) that required biopsy were included. CEDEM examinations were performed on a modified prototype machine. Acquired HE and low energy raw data images were registered non-rigidly to compensate for possible subtle tissue motion. Subtracted CEDEM images were generated via weighted subtraction, using a fully automatic, locally adjusted tissue thickness-dependent subtraction factor to avoid over-subtraction at the breast border. Two observers evaluated the MG and CEDEM images according to ACR BI-RADS in two reading sessions. Results were correlated with histopathology. RESULTS: Seven patients with benign and eight with malignant findings were included. All malignant lesions showed a strong contrast enhancement. BI-RADS assessment was altered in 66.6 % through the addition of CEDEM, resulting in increased overall accuracy. With CEDEM, additional lesions were depicted and false-positive rate was reduced compared to MG. CONCLUSIONS: CEDEM using Ti filtering with 49 kVp for HE exposures is feasible in a clinical setting. The proposed image-processing algorithm has the potential to reduce artefacts and improve CEDEM images. KEY POINTS: * CEDEM with a titanium filter is feasible in a clinical setting. * Breast thickness-dependent image subtraction has the potential to improve CEDEM images. * The proposed image-processing algorithm reduces artefacts. PMID- 26373755 TI - Effectiveness and safety of computed tomography-guided radiofrequency ablation of renal cancer: a 14-year single institution experience in 203 patients. AB - OBJECTIVES: To define effectiveness and safety of CT-guided radiofrequency ablation (RFA) of renal tumours and prognostic indicators for treatment success. METHODS: Patients with a single treatment of a solitary, biopsy-proven renal tumour with intent to cure over a 14-year period were included (n = 203). Probability of residual disease over time, complication rates and all-cause mortality were assessed in relation to multiple variables. RESULTS: Mean tumour size was 2.5 cm (range 1.0-6.0). Mean follow-up was 34.1 months (range 1-131). There was an increase in likelihood of residual disease for tumours >=3.5 cm (P < 0.05), clear cell subtype of renal cell carcinoma (P <= 0.005) and maximum treatment temperature <=70 degrees C (P < 0.05). There was a decrease in likelihood of residual disease for exophytic tumours (P = 0.01) and no difference based on age, gender, tumour location or type of radio freqency (RF) electrode used. Major complications occurred in 3.9 %. Median post-treatment survival was 7 years for patients with tumours <4 cm, and 5-year overall survival was 80 %. Probability of minor complication increased with tumour size (P = 0.03), as did all-cause mortality (P = 0.005). CONCLUSIONS: CT-guided RFA is safe and effective for early-stage renal cancer, particularly for exophytic tumours measuring <3.5 cm. Overall 5-year survival with tumours <4 cm is comparable to partial nephrectomy. KEY POINTS: * Prognostic indicators for success of CT-guided RFA of renal tumours are reported. * Tumour size >=3.5 cm confers an increased risk for residual tumour. * Clear cell renal cell carcinoma subtype confers increased risk for residual tumour. * Tmax <70 degrees C within the ablation zone confers increased risk for residual tumour. * Exophytic tumours have a lower probability of residual disease. PMID- 26373756 TI - Quantitative assessment of hepatic function: modified look-locker inversion recovery (MOLLI) sequence for T1 mapping on Gd-EOB-DTPA-enhanced liver MR imaging. AB - OBJECTIVES: To determine whether multislice T1 mapping of the liver using a modified look-locker inversion recovery (MOLLI) sequence on gadoxetic acid enhanced magnetic resonance imaging (MRI) can be used as a quantitative tool to estimate liver function and predict the presence of oesophageal or gastric varices. METHODS: Phantoms filled with gadoxetic acid were scanned three times using MOLLI sequence to test repeatability. Patients with chronic liver disease or liver cirrhosis who underwent gadoxetic acid-enhanced liver MRI including MOLLI sequence at 3 T were included (n = 343). Pre- and postcontrast T1 relaxation times of the liver (T1liver), changes between pre- and postcontrast T1liver (DeltaT1liver), and adjusted postcontrast T1liver (postcontrast T1liver T1spleen/T1spleen) were compared among Child-Pugh classes. In 62 patients who underwent endoscopy, all T1 parameters and spleen sizes were correlated with varices. RESULTS: Phantom study showed excellent repeatability of MOLLI sequence. As Child-Pugh scores increased, pre- and postcontrast T1liver were significantly prolonged (P < 0.001), and DeltaT1liver and adjusted postcontrast T1liver decreased (P < 0.001). Adjusted postcontrast T1liver and spleen size were independently associated with varices (R (2) = 0.29, P < 0.001). CONCLUSIONS: T1 mapping of the liver using MOLLI sequence on gadoxetic acid-enhanced MRI demonstrated potential in quantitatively estimating liver function, and adjusted postcontrast T1liver was significantly associated with varices. KEY POINTS: * T1 mapping using MOLLI sequence can be achieved within a breath-hold. * T1liver measured by MOLLI sequence provided excellent short-term repeatability. * Precontrast and postcontrast T1liver were significantly prolonged as Child-Pugh scores increased. * Adjusted postcontrast T1liver and spleen size were independently associated with varices. PMID- 26373757 TI - Metastatic patterns and metastatic sites in mucosal melanoma: a retrospective study. AB - OBJECTIVES: Melanomas arising from mucosa are rare and associated with a poor prognosis. This study aims to provide an analysis of metastatic pathways, time intervals, factors influencing metastatic spread and organs for distant metastases. METHODS: A total of 116 patients with mucosal melanomas of different sites were included. The mean follow-up interval was 47 +/- 52 months. Patients were assigned to two different metastatic pathways, either presenting loco regional lymph node metastases as first spread or direct distant metastases. The distribution of distant metastases was assessed. RESULTS: Twenty-six patients presented with a pre-existing metastatic spread and were not assigned to pathways. Of the included patients, 44 developed metastases after treatment of the primary tumour; 25 patients directly developed distant metastases; 16 patients developed regional lymph node metastases prior to distant metastases. Location of the primary tumour in the upper airway or GI tract and advanced T stage were significant risk factors of direct distant metastases. Distant metastases are mainly located in the lung, the liver and non-regional lymph nodes. CONCLUSIONS: Mucosal melanomas show a high rate of direct distant metastases rather than regional lymph node metastases. Thus the follow-up should always include a whole-body cross-sectional imaging in high-risk tumours. KEY POINTS: * Mucosal melanomas show a high rate of direct distant metastases. * T stage and primary location are predictors for direct distant metastases. * Distant metastases were mainly found in lung, liver and lymph nodes. * Follow-up of a high-risk mucosal melanoma should include whole-body imaging. PMID- 26373758 TI - Role of MRI in the early diagnosis of tubal ectopic pregnancy. AB - OBJECTIVE: To determine the role of MRI in the early diagnosis of tubal ectopic pregnancy (EP). METHODS: Clinical and MRI features of 27 cases of tubal pregnancy were reviewed. RESULTS: A thick-walled gestational sac (GS)-like structure was demonstrated lateral to the uterus in all cases. On T2-weighted images, the thick wall typically exhibited 3 discrete rings in 22 cases (81 %), among which 17 cases (63 %) displayed small vessels and 6 cases (33 %) exhibited small areas of fresh haemorrhage inside the thick wall. The contents demonstrated non-specific liquid in 26 %, papillary solid components in 56 %, and fresh blood or fluid fluid level in 19 % of the cases. Dilatation of the affected fallopian tube associated with hematosalpinx was demonstrated in 18 cases (67 %) and marked enhancement of the tubal wall was observed in 22 cases (81 %). No correlation was found between the size of the GS and the estimated gestational age (r = 0.056). CONCLUSION: MRI plays an important role in the early diagnosis and management of tubal pregnancy. The characteristic MRI features include a GS-like structure with a "three rings" appearance on T2-weighted images, presence of solid components in the sac, dilatation of the affected fallopian tube with hematosalpinx, and tubal wall enhancement. KEY POINTS: * MR imaging has served as a problem-solving procedure in ectopic pregnancy. * MR imaging features can be criteria for early diagnosis of tubal pregnancy. * Detailed assessment of ectopic implantation is necessary for management decision-making. PMID- 26373759 TI - Accelerated magnetic resonance diffusion tensor imaging of the median nerve using simultaneous multi-slice echo planar imaging with blipped CAIPIRINHA. AB - PURPOSE: To investigate the feasibility of MR diffusion tensor imaging (DTI) of the median nerve using simultaneous multi-slice echo planar imaging (EPI) with blipped CAIPIRINHA. MATERIALS AND METHODS: After federal ethics board approval, MR imaging of the median nerves of eight healthy volunteers (mean age, 29.4 years; range, 25-32) was performed at 3 T using a 16-channel hand/wrist coil. An EPI sequence (b-value, 1,000 s/mm(2); 20 gradient directions) was acquired without acceleration as well as with twofold and threefold slice acceleration. Fractional anisotropy (FA), mean diffusivity (MD) and quality of nerve tractography (number of tracks, average track length, track homogeneity, anatomical accuracy) were compared between the acquisitions using multivariate ANOVA and the Kruskal-Wallis test. RESULTS: Acquisition time was 6:08 min for standard DTI, 3:38 min for twofold and 2:31 min for threefold acceleration. No differences were found regarding FA (standard DTI: 0.620 +/- 0.058; twofold acceleration: 0.642 +/- 0.058; threefold acceleration: 0.644 +/- 0.061; p >= 0.217) and MD (standard DTI: 1.076 +/- 0.080 mm(2)/s; twofold acceleration: 1.016 +/- 0.123 mm(2)/s; threefold acceleration: 0.979 +/- 0.153 mm(2)/s; p >= 0.074). Twofold acceleration yielded similar tractography quality compared to standard DTI (p > 0.05). With threefold acceleration, however, average track length and track homogeneity decreased (p = 0.004-0.021). CONCLUSION: Accelerated DTI of the median nerve is feasible. Twofold acceleration yields similar results to standard DTI. KEY POINTS: * Standard DTI of the median nerve is limited by its long acquisition time. * Simultaneous multi-slice acquisition is a new technique for accelerated DTI. * Accelerated DTI of the median nerve yields similar results to standard DTI. PMID- 26373760 TI - Late gadolinium enhancement cardiac imaging on a 3T scanner with parallel RF transmission technique: prospective comparison of 3D-PSIR and 3D-IR. AB - OBJECTIVE: To qualitatively and quantitatively compare different late gadolinium enhancement (LGE) sequences acquired at 3T with a parallel RF transmission technique. METHODS: One hundred and sixty participants prospectively enrolled underwent a 3T cardiac MRI with 3 different LGE sequences: 3D Phase-Sensitive Inversion-Recovery (3D-PSIR) acquired 5 minutes after injection, 3D Inversion Recovery (3D-IR) at 9 minutes and 3D-PSIR at 13 minutes. All LGE-positive patients were qualitatively evaluated both independently and blindly by two radiologists using a 4-level scale, and quantitatively assessed with measurement of contrast-to-noise ratio and LGE maximal surface. Statistical analyses were calculated under a Bayesian paradigm using MCMC methods. RESULTS: Fifty patients (70 % men, 56yo +/- 19) exhibited LGE (62 % were post-ischemic, 30 % related to cardiomyopathy and 8 % post-myocarditis). Early and late 3D-PSIR were superior to 3D-IR sequences (global quality, estimated coefficient IR > early-PSIR : -2.37 CI = [-3.46 ; -1.38], prob(coef > 0) = 0 % and late-PSIR > IR : 3.12 CI = [0.62 ; 4.41], prob(coef > 0) = 100 %), LGE surface estimated coefficient IR > early PSIR: -0.09 CI = [-1.11; -0.74], prob(coef > 0) = 0 % and late-PSIR > IR : 0.96 CI = [0.77; 1.15], prob(coef > 0) = 100 %). Probabilities for late PSIR being superior to early PSIR concerning global quality and CNR were over 90 %, regardless of the aetiological subgroup. CONCLUSIONS: In 3T cardiac MRI acquired with parallel RF transmission technique, 3D-PSIR is qualitatively and quantitatively superior to 3D-IR. KEY POINTS: * Late gadolinium enhancement is an essential part of a cardiac MRI examination * PSIR and IR sequences are the two possible options for LGE imaging * At 3T with parallel RF transmission, PSIR sequences are significantly better * One LGE sequence is sufficient, allowing an optimization of the acquisition time. PMID- 26373761 TI - Using intravoxel incoherent motion MR imaging to study the renal pathophysiological process of contrast-induced acute kidney injury in rats: Comparison with conventional DWI and arterial spin labelling. AB - OBJECTIVES: To investigate the potential of intravoxel incoherent motion (IVIM) to assess the renal pathophysiological process in contrast-induced acute kidney injury (CIAKI). METHODS: Twenty-seven rats were induced with CIAKI model, six rats were imaged longitudinally at 24 h prior to and 30 min, 12, 24, 48, 72 and 96 h after administration; three rats were randomly chosen from the rest for serum creatinine and histological studies. D, f, D* and ADC were calculated from IVIM, and renal blood flow (RBF) was obtained from arterial spin labelling (ASL). RESULTS: A progressive reduction in D and ADC was observed in cortex (CO) by 3.07 and 8.62 % at 30 min, and by 25.77 and 28.16 % at 48 h, respectively. A similar change in outer medulla (OM) and inner medulla (IM) was observed at a later time point (12-72 h). D values were strongly correlated with ADC (r = 0.885). As perfusion measurement, a significant decrease was shown for f in 12-48 h and an increase in 72-96 h. A slightly different trend was found for D*, which was decreased by 26.02, 21.78 and 10.19 % in CO, OM and IM, respectively, at 30 min. f and D* were strongly correlated with RBF in the cortex (r = 0.768, r = 0.67), but not in the medulla. CONCLUSIONS: IVIM is an effective imaging tool for monitoring progress in renal pathophysiology undergoing CIAKI. KEY POINTS: * IVIM analysis permits separate quantification of diffusion and perfusion. * IVIM can provide useful biomarkers ifor changes in renal pathophysiology. * IVIM can be useful for monitoring progress in renal pathophysiology undergoing CIAKI. PMID- 26373762 TI - Endovascular management of massive post-partum haemorrhage in abnormal placental implantation deliveries. AB - OBJECTIVES: To retrospectively evaluate safety and efficacy of pelvic artery embolisation (PAE) in post-partum haemorrhage (PPH) in abnormal placental implantation (API) deliveries. METHODS: From January 2009 to November 2013, 12 patients with API and intractable intraoperative PPH underwent PAE after caesarean delivery to control a haemorrhage (in four of these cases after hysterectomy). Arterial access was obtained prior to the delivery; PAE was performed in the obstetrics operating room by an interventional radiologist that was present with an interventional radiology (IR) team during the delivery. RESULTS: PAE was successful in preventing bleeding and avoid hysterectomy in four cases (group A). Uterine atony and disseminated intravascular coagulation caused failure of PAE requiring hysterectomy in four patients (group B). PAE prevented bleeding post-hysterectomy in the remaining four cases (group C). Technical success (cessation of contrast extravasation on angiography or occlusion of the selected artery) was 100 %. Maternal and foetal mortality and morbidity were 0 %. CONCLUSIONS: PAE is a minimal invasive technique that may help to prevent hysterectomy and control PPH in API pregnancies without complications. Embolisation should be performed on an emergency basis. For such cases, an IR team on standby in the obstetrics theatre may be useful to prevent hysterectomy, blood loss and limit morbidity. KEY POINTS: * Endovascular treatment is a validated technique in post-partum haemorrhage. * Abnormal placental implantation is a risk factor for post-partum haemorrhage. * We propose an interventional radiologist standby in the delivery room. PMID- 26373763 TI - Differentiation of intrahepatic mass-forming cholangiocarcinoma from hepatocellular carcinoma on gadoxetic acid-enhanced liver MR imaging. AB - OBJECTIVES: To determine the different imaging features of intrahepatic mass forming cholangiocarcinoma (IMCC) from hepatocellular carcinoma (HCC) on gadoxetic acid-enhanced magnetic resonance imaging (MRI). METHODS: This retrospective study was institutional review board approved and the requirement for informed consent was waived. Patients who underwent gadoxetic acid-enhanced MRI with histologically confirmed IMCCs (n = 46) or HCCs (n = 58) were included. Imaging features of IMCCs and HCCs on gadoxetic acid-enhanced MRI including T2- and T1-weighted, diffusion weighted images, dynamic study and hepatobiliary phase (HBP) images were analyzed. Univariate and multivariate logistic regression analyses were performed to identify relevant differentiating features between IMCCs and HCCs. RESULTS: Multivariate analysis revealed heterogeneous T2 signal intensity and a hypointense rim on the HBP as suggestive findings of IMCCs and the wash-in and "portal wash-out" enhancement pattern as well as focal T1 high signal intensity foci as indicative of HCCs (all, p < 0.05). When we combined any three of the above four imaging features, we were able to diagnose IMCCs with 94 % (43/46) sensitivity and 86 % (50/58) specificity. CONCLUSIONS: Combined interpretation of enhancement characteristics including HBP images, morphologic features, and strict application of the "portal wash-out" pattern helped more accurate discrimination of IMCCs from HCCs. KEY POINTS: * Analysis of enhancement characteristics helped accurate discrimination of IMCCs from HCCs. * Wash-out should be determined on the PVP of gadoxetic acid-enhanced MRI. * A hypointense rim on the HBP was a significant finding of IMCCs. PMID- 26373764 TI - Ultrasound-guided percutaneous fine-needle aspiration of solid pancreatic neoplasms: 10-year experience with more than 2,000 cases and a review of the literature. AB - OBJECTIVES: To evaluate the diagnostic accuracy and complication rate of percutaneous ultrasound-guided fine-needle aspiration (US-FNA) of solid pancreatic neoplasms through the analysis of 10-year experiences of two centres. METHODS: Clinical, radiological and pathologic data of 2,024 patients with solid pancreatic masses who underwent US-FNAs were retrospectively evaluated. Indications for aspiration were: unresectable lesions before neo-adjuvant therapy; doubtful imaging findings; and suspicion of uncommon neoplasms with prognostic or therapeutic implications such as metastases or lymphoma. US-FNAs were performed using aspiration needles with a cytopathologist present in centre 1. In centre 2, cytologic samples were collected with Chiba needles and separately evaluated by a cytopathologist. RESULTS: US-FNA had a diagnostic sample rate of 92.2 % (centre 1: 95.9 %; centre 2: 87.2 %). US-FNA repetition after non-diagnostic samples provided a diagnosis in 86.3 % of cases. Sensitivity, specificity, positive and negative predictive values, and accuracy were 98.7 %, 100 %, 100 %, 75.5 %, and 98.7 %, respectively. The complication rate was 0.8 %. CONCLUSIONS: Percutaneous US-FNA is a sensitive, accurate and safe method for the invasive diagnosis of solid pancreatic neoplasms. The use of aspiration needles and the on-site presence of a cytopathologist may lead to a high rate of diagnostic samples, thus reducing the need for US-FNA repetition. KEY POINTS: * Percutaneous ultrasound-guided fine-needle aspiration of pancreatic neoplasms is sensitive and accurate. * The short-term complication rate of percutaneous ultrasound-guided fine-needle aspiration is low. * Technical aspects may influence the rate of diagnostic samples. PMID- 26373765 TI - Intravoxel incoherent motion magnetic resonance imaging to predict vesicoureteral reflux in children with urinary tract infection. AB - OBJECTIVES: To compare the diffusion parameters of intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) between the "reflux" and the "non-reflux" kidneys, and to evaluate the feasibility of using IVIM DWI to predict vesicoureteral reflux (VUR) in children with a urinary tract infection (UTI). METHODS: Eighty-three kidneys from 57 pediatric patients with a UTI were classified into "reflux" and "non-reflux" groups according to voiding cystourethrography (VCUG) results. The apparent diffusion coefficient (ADC), true diffusion coefficient (D), pseudo-diffusion coefficient (D*), and perfusion fraction (PF) were measured and compared in the renal pelvis of both groups. Four indices (D*/ADC, PF/ADC, D*/D, and PF/D) were calculated and receiver operating characteristic (ROC) curve analyses were performed. RESULTS: VURs were detected on VCUG in 21 kidneys. PF and D* were significantly higher in the "reflux" group than in the "non-reflux" group. The indices were all significantly higher. The PF/D index showed the best diagnostic performance in predicting VUR in children with UTI (Az = 0.864). CONCLUSION: PF and D* were significantly higher in the "reflux" kidney than in the "non-reflux" kidney. Our new index (PF/D) could prove useful for predicting VUR. KEY POINTS: * IVIM DWI is both radiation-free and contrast media-free. * IVIM DWI index is easily calculated by combining diffusion parameters. * IVIM DWI may help predict VUR in children with UTI. * PF is significantly higher in the "reflux" than the "non-reflux" kidneys. * A new VUR index, PF/D could prove useful for predicting VUR. PMID- 26373766 TI - Brief Report: Translation and Adaptation of the Theory of Mind Inventory to Spanish. AB - The Theory of Mind Inventory is an informant measure designed to evaluate children's theory of mind competence. We describe the translation and cultural adaptation of the inventory by the following process: (1) translation from English to Spanish by two independent certified translators; (2) production of an agreed version by a multidisciplinary committee of experts; (3) back-translation to English of the agreed version by an independent translator; (4) discussion of the semantic, idiomatic, and cultural equivalence of the final version; (5) elaboration of the final test; (6) pilot test on 24 representatives of the autism spectrum disorders population and 24 representatives of typically developing children. The steps were conducted satisfactorily, producing the final version in Spanish, which showed good psychometric properties. PMID- 26373767 TI - Applied Behavior Analysis is a Science and, Therefore, Progressive. AB - Applied behavior analysis (ABA) is a science and, therefore, involves progressive approaches and outcomes. In this commentary we argue that the spirit and the method of science should be maintained in order to avoid reductionist procedures, stifled innovation, and rote, unresponsive protocols that become increasingly removed from meaningful progress for individuals diagnosed with autism spectrum disorder (ASD). We describe this approach as progressive. In a progressive approach to ABA, the therapist employs a structured yet flexible process, which is contingent upon and responsive to child progress. We will describe progressive ABA, contrast it to reductionist ABA, and provide rationales for both the substance and intent of ABA as a progressive scientific method for improving conditions of social relevance for individuals with ASD. PMID- 26373768 TI - Maternal Psychiatric Disorder and the Risk of Autism Spectrum Disorder or Intellectual Disability in Subsequent Offspring. AB - Psychiatric disorders are more common in the mothers of children with autism spectrum disorder (ASD) or intellectual disability (ID) after the birth of their child. We aimed to assess the relationship between women's psychiatric contacts and subsequent offspring with ASD/ID. We linked three Western Australian registers to investigate pre-existing maternal outpatient psychiatric contacts and the odds of ASD/ID in a subsequent child. Women with a previous outpatient psychiatric contact were more than twice as likely to have a child with ASD [OR 2.07 (95 % CI 1.7, 2.6)] or ID [OR 2.31 (2.1, 2.6)]. Further research exploring the effect on pregnancy outcomes of medications prescribed to women with psychiatric disorders is implicated. PMID- 26373769 TI - The role of offset stems in revision knee arthroplasty. AB - Revision total knee arthroplasty (TKA) represents a technically challenging procedure. The use of an offset stem extension can help in addressing some of the difficulties that can be encountered during surgery and, in particular, anatomical mismatch, malalignment, and gap balancing. Different offset stem extensions are available and can be classified according to four parameters: modularity, location of the offset, direction, and size of the displacement. Offset stem extensions can assist with implant alignment on the metaphysis if there is an offset diaphysis, can avoid medial-lateral or anterior-posterior component overhang, can reduce the incidence of coronal or sagittal malalignment, and can help in balancing the flexion and extension spaces by effectively translating the components. The aim of this study is to give an overview of the currently available evidence regarding the use of offset stem extensions in revision TKA as well as some useful surgical tips. PMID- 26373770 TI - Level of constraint in revision knee arthroplasty. AB - Revision total knee arthroplasty (TKA) in the setting of major bone deficiency and/or soft tissue laxity might require increasing levels of constraint to restore knee stability. However, increasing the level of constraint not always correlates with mid-to-long-term satisfactory results. Recently, modular components as tantalum cones and titanium sleeves have been introduced to the market with the goal of obtaining better fixation where bone deficiency is an issue; theoretically, satisfactory meta-diaphyseal fixation can reduce the mechanical stress at the level of the joint line, reducing the need for high levels of constraint. This article reviews the recent literature on the surgical management of the unstable TKA with the goal to propose a modern surgical algorithm for adult reconstruction surgeons. PMID- 26373772 TI - Viral neuronotropism is important in the pathogenesis of Murray Valley encephalitis. PMID- 26373773 TI - Angioembolisation of a Bleeding Meckel's Diverticulum. AB - We describe the diagnosis of an adult who presented with hematochezia. This was investigated and found to be from a bleeding Meckel's diverticulum. As this condition is rare in adults, there is no consensus regarding the optimal mode of management. We propose the use of angioembolisation in the diagnostic and therapeutic management of this condition. Our case showed that this strategy is indeed feasible and can achieve good short-term control, allowing for definitive surgery in an elective setting. PMID- 26373771 TI - Cartilage repair techniques in the knee: stem cell therapies. AB - Among the surgical options for large full-thickness chondral injuries, cell-based therapy has been practiced and its satisfactory outcomes have been reported. One area that appears promising is cell-based therapies utilizing stem cells. Various tissues within the human body contain mesenchymal stem cells (MSCs) from where these can be harvested. These include bone marrow, adipose, synovium, peripheral blood, and umbilical cord. In this article, both preclinical animal studies and clinical studies dealing with the use of MSCs for cartilage repair of the knee are reviewed. Majority of the clinical papers have shown promising results; however, there are a limited number of studies of high evidence level. Clinical significance of the stem cell therapy as compared to other surgical options as well as optimization of the procedure in terms of cell type and delivery method is still to be determined. PMID- 26373774 TI - Stigmatisation, perceived barriers to care, help seeking and the mental health of British Military personnel. AB - INTRODUCTION: The relationship between mental health symptoms, stigmatising beliefs about mental health and help seeking is complex and poorly understood. METHOD: 1636 UK Armed Forces personnel provided study data immediately after deployment (T1) and approximately 6 months later (T2). Stigmatising beliefs were assessed using an eight-item scale previously used in studies of UK military personnel. Symptoms of probable common mental disorder, probable post-traumatic stress disorder and subjective stressful, emotional, relationship and family problems were evaluated at T1 and T2. Help seeking during deployment was assessed at T1 and post-deployment help seeking at T2. Alcohol use and subjective alcohol problems were assessed at T2 only. RESULTS: Reporting a probable mental health disorder or potentially harmful alcohol use following deployment was both significantly associated with higher levels of stigmatising beliefs. The reported degree of stigma was associated with changes in mental health symptom levels; compared to those who were never classified as a probable mental health disorder case, recovered cases experienced significantly lower levels of stigmatisation, whereas new onset cases reported significantly higher levels. CONCLUSION: The way that individuals report mental health stigmatisation is not static; rather stigma fluctuates in proportion to the frequency and severity of psychological symptoms. These results suggest that public health stigma-reduction strategies which aim to promote engagement with mental health services should be focused towards people who are experiencing worsening mental health. Our results suggest that willing volunteers who have recovered from a mental-ill-health episode may be well placed to assist in the delivery of such a strategy. PMID- 26373775 TI - Clustering of adversity in young adults on disability pension due to mental disorders: a latent class analysis. AB - PURPOSE: Mental disorders are the leading cause of work disability among young adults. This study examined whether distinct classes could be identified among young adults on the basis of medical history before receiving a disability pension due to a mental disorder. METHODS: Medical history was obtained from pension applications and attached medical certificates for 1163 individuals aged 18-34 years who, in 2008, received a disability pension due to a mental disorder. Using latent class analysis, 10 clinical and individual adversities and their associations with sex, age and diagnostic category were examined. RESULTS: Three classes were identified: childhood adversity (prevalence, 33%), comorbidity (23%), and undefined (44%). The childhood adversity class was characterized by adverse events and symptoms reported during childhood and it associated with depressive disorders. The comorbidity class was characterized by comorbid mental disorders, suicide attempts and substance abuse and associated with younger age and bipolar disorder. The undefined class formed no distinct profile; individuals in this class had the lowest number of adversities and it associated with psychotic disorders. CONCLUSIONS: The identification of subgroups characterized by childhood circumstances and comorbidity may help planning of prevention and support practices for young adults with mental disorders and risk of work disability. PMID- 26373777 TI - Diastereoselective synthesis of spiro[benzo[d]pyrrolo[2,1-b]thiazole-3,3' indolines] via cycloaddition reaction of N-phenacylbenzothiazolium bromides and 3 methyleneoxindoles. AB - The domino cycloaddition reactions of N-phenacylbenzothiazolium bromides with 3 phenacylideneoxindoles or ethyl 2-(2-oxoindolin-3-ylidene)acetates in ethanol at room temperature in the presence of triethylamine as a base afforded functionalized spiro[benzo[d]pyrrolo[2,1-b]thiazole-3,3'-indolines] in good yields and with high diastereoselectivity. The similar reactions of N phenacylthiazolium bromides with 3-phenacylideneoxindoles resulted in the corresponding functionalized spiro[indoline-3,7'-pyrrolo[2,1-b]thiazoles] in satisfactory yields and also with high diastereoselectivity. PMID- 26373776 TI - Selective nonresponse bias in population-based survey estimates of drug use behaviors in the United States. AB - PURPOSE: There is a trend of decreasing response rates in population surveys, and selective nonresponse represents a major source of potential bias in population based survey estimates of drug use behaviors, especially estimates based on longitudinal designs. METHODS: This study compared baseline substance use behaviors among initial respondents who did respond (n = 34,653) and did not respond (n = 8440) to a 3-year follow-up interview in a prospective study of the general U.S. adult population. Differences in nonresponse rates were assessed as a function of past-year drug use behaviors both before and after adjustment for socio-demographic differences potentially associated with these behaviors, and the effects of interactions of the socio-demographic characteristics with the drug use behaviors were assessed in multivariate logistic regression models for response at the 3-year follow-up. RESULTS: Weighted and unweighted nonresponse rates varied between alcohol users and users of other drugs such as cocaine and marijuana, with rates of nonresponse being higher in the latter drug categories. There were also significant differences in nonresponse rates as a function of frequency of use and demographics. More specifically, being married tends to reduce the probability of non-response, while older age, being male, being Asian or Hispanic, and having lower education all substantially increase the probability of nonresponse at Wave 2, even after controlling for relevant covariates. CONCLUSIONS: This study provides the substance abuse field with a methodology that users of longitudinal data can apply to test the sensitivity of their inferences to assumptions about attrition patterns. PMID- 26373778 TI - Microfabrication of scaffold-free tissue strands for three-dimensional tissue engineering. AB - In this note, we report a practical and efficient method based on a coaxial extrusion and microinjection technique for biofabrication of scaffold-free tissue strands. Tissue strands were obtained using tubular alginate conduits as mini capsules with well-defined permeability and mechanical properties, where their removal by ionic decrosslinking allowed the formation of scaffold-free cell aggregates in the form of cylindrical strands with well-defined morphology and geometry. Rat dermal fibroblasts and mouse insulinoma beta TC3 cells were used to fabricate both single-cellular and heterocellular tissue strands with high cell viability, self-assembling capability and the ability to express cell-specific functional markers. By taking advantage of tissue self-assembly, we succeeded in guiding the fusion of tissue strands to fabricate larger tissue patches. The presented approach enables fabrication of cell aggregates with controlled dimensions allowing highly long strands, which can be used for various applications, including fabrication of scale-up complex tissues and of tissue models for drug screening and cancer studies. PMID- 26373779 TI - Coronarographyc detection of double right coronary artery arising from two separated ostia in the right sinus of Valsalva. PMID- 26373780 TI - The prognostic value of different biomarkers in predicting clinical outcome in discharged heart failure patients. PMID- 26373781 TI - The predictive value of plasma biomarkers in discharged heart failure patients: role of plasma NT-proBNP. AB - BACKGROUND: Natriuretic peptides (NPs) have demonstrated their value to support clinical diagnosis of heart failure (HF); furthermore they are also studied for their prognostic role using them to guide appropriate management strategies. The present review gathers available evidence on prognostic role of N-terminal pro-B type natriuretic peptide (NT-proBNP) in patients hospitalized for acute decompensated heart failure (ADHF). METHODS: We searched Medline for English language studies with the sequent key-words: "acute heart failure/acute decompensated heart failure", "NT-proBNP/N-terminal pro-B type natriuretic peptide" and "prognosis/mortality/readmission". RESULTS: Almost 30 studies were included. NT-proBNP plasma levels at admission are strongly associated with all cause short-term mortality (2-3 months), mid-term (6-11 months) or long- term mortality (more than one year) of follow-up. Regarding the prognostic power on cardiac death fewer data are available with uncertain results. NT-proBNP at discharge demonstrated its prognostic role for all-cause mortality at mid and long-term follow-up. The relation between NT-proBNP at discharge and cardiovascular mortality or composite end-point is under investigation. A decrease in NT-proBNP values during hospitalization provided prognostic prospects mainly for cardiovascular mortality and HF readmission. A 30% variation in NT proBNP levels during in-hospital stay seemed to be an optimal cut-off for prognostic role. CONCLUSION: SNT-proBNP plasma levels proved to have a strong correlation with all-cause mortality, cardiovascular mortality, morbidity and composite outcomes in patients discharged after an ADHF. A better definition of the correct time of serial measurements and the cut-off values might be the challenge for the future investigations. PMID- 26373783 TI - Lacimonas salitolerans gen. nov., sp. nov., isolated from surface water of a saline lake. AB - A Gram-stain-negative bacterium, strain TS-T30T, was isolated from a saline lake (Lake Tuosu) in Qaidam basin, Qinghai province, China, and its taxonomic position was determined by using a polyphasic approach. Cells were non-spore-forming rods, non-motile, 0.8-1.4 MUm wide and 1.9-4.0 MUm long. Strain TS-T30T was strictly heterotrophic and aerobic. Catalase- and oxidase-positive. Growth was observed in the presence of 0.5-11.0 % (w/v) NaCl (optimum 3.0 %), and at 10-35 degrees C (optimum 25 degrees C) and pH 6.5-10.0 (optimum pH 8.5). Strain TS-T30T contained C18 : 1omega7c as the only predominant fatty acid. The major respiratory quinone was Q-10. The DNA G+C content was 62 mol% (Tm). Phylogenetic trees based on 16S rRNA gene sequences showed that strain TS-T30T formed a distinct lineage that was independent of other most closely related genera: Lutimaribacter (95.2-95.9 % 16S rRNA gene sequence similarities), Poseidonocella (95.4 %), Ruegeria (92.8-94.9 %), Marivita (93.6-94.9 %), Seohaeicola (94.7 %), Sediminimonas (94.7 %), Shimia (93.9-94.7 %), Oceanicola (92.6-94.5 %) and Roseicyclus (94.5 %). The major polar lipids were phosphatidylglycerol, one unidentified phospholipid and an unknown aminolipid; phosphatidylcholine was not detected. These data demonstrated that strain TS-T30T represents a novel species of a new genus in the family Rhodobacteraceae, for which the name Lacimonas salitolerans gen. nov., sp. nov. is proposed. The type strain of the type species is TS-T30T ( = CGMCC 1.12477T = NBRC 110969T). PMID- 26373782 TI - Seeing the world differently: variability in the photosensory mechanisms of two model fungi. AB - Light plays an important role for most organisms on this planet, serving either as a source of energy or information for the adaptation of biological processes to specific times of day. The fungal kingdom is estimated to contain well over a million species, possibly 10-fold more, and it is estimated that a majority of the fungi respond to light, eliciting changes in several physiological characteristics including pathogenesis, development and secondary metabolism. Two model organisms for photobiological studies have taken centre-stage over the last few decades--Neurospora crassa and Aspergillus nidulans. In this review, we will first discuss our understanding of the light response in N. crassa, about which the most is known, and will then juxtapose N. crassa with A. nidulans, which, as will be described below, provides an excellent template for understanding photosensory cross-talk. Finally, we will end with a commentary on the variability of the light response among other relevant fungi, and how our molecular understanding in the aforementioned model organisms still provides a strong base for dissecting light responses in such species. PMID- 26373784 TI - Bile duct surgery in the treatment of hepatobiliary and gallbladder malignancies: effects of hepatic and vascular resection on outcomes. AB - BACKGROUND: Resection of the bile duct is required for the treatment of cholangiocarcinoma and is sometimes indicated in resections of liver and gallbladder malignancies. The goal of this retrospective review was to characterize surgical outcomes in patients submitted to bile duct resection for malignancy when additional procedures, specifically hepatic or vascular resections, were performed. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was searched to identify a total of 747 patients who underwent: (i) biliary-enteric anastomosis (BEA) only (Group 1, n = 266); (ii) BEA with hepatic resection (Group 2, n = 439), or (iii) BEA with hepatic and vascular resection (Group 3, n = 42). Postoperative outcomes were compared and regression-adjusted risk factors were analysed to produce observed and expected (O/E) morbidity and mortality ratios. RESULTS: The performance of hepatic and vascular resections significantly increased rates of overall morbidity (P < 0.001) and mortality (P = 0.021). Risk-adjusted O/E mortality ratios in Groups 1, 2 and 3 were 1.44 [95% confidence interval (CI) 0.84-2.30], 2.16 (95% CI 1.51-2.98) and 5.92 (95% CI 2.54-11.66), respectively. Multivariate analysis identified Group 2 (P < 0.001) and Group 3 (P = 0.001) status as independent predictors of morbidity, and Group 3 status (P = 0.008) as independently associated with mortality. More than 30% of deaths were associated with pulmonary complications and septic shock. CONCLUSIONS: The addition of hepatic and vascular resections to bile duct resection significantly increased morbidity and mortality. The high O/E mortality ratios for patients in Groups 2 and 3 suggest these outcomes can be improved. PMID- 26373786 TI - Facilitators and barriers in expanding scope of practice: findings from a national survey of Irish nurses and midwives. AB - AIMS AND OBJECTIVES: The aim was to examine current scope of practice among nurses and midwives in Ireland. The objectives were to describe practitioners' self-reported facilitators and barriers to expanding scope of practice and to develop a scope of practice barriers scale. BACKGROUND: Regulatory authorities permit practice expansion, so long as it falls within accepted parameters of scope of practice. Enduring difficulties in relation to scope of practice include the difficulty of balancing practice restriction with practice expansion. DESIGN: A postal survey design was used to examine registered nurses' and midwives' current scope of practice, including their experiences of facilitators and barriers to expanding practice. METHODS: A stratified random sample of registered nurses and midwives in Ireland was surveyed using the Scope-QB, a 19-item self report scope of practice barriers scale. RESULTS: Based on a sample of 1010 respondents, the self-reported perceived barriers to practice expansion included fear of legal consequences, time restrictions and lack of remuneration. Professional satisfaction, patients' needs, organisational support and having access to continuing professional education were perceived as facilitators of practice expansion. Older nurses and midwives as well as nurses and midwives holding more senior promotional grades, such as clinical nurse manager grades, perceived fewer barriers than their younger and more junior counterparts. CONCLUSIONS: Nurses and midwives continue to experience difficulties in relation to expanding their practice. Practitioners can operate to optimal scope of practice when practitioner-centred and workplace-based circumstances are optimal. The optimal circumstances for practice expansion exist when the facilitators of practice expansion outweigh the barriers. RELEVANCE TO CLINICAL PRACTICE: Given the critical role that nurses and midwives play in modern health services, it is important that they are empowered and enabled to expand their practice and to work to full scope of practice when patient needs and service requirements warrant it. PMID- 26373787 TI - Near-Infrared Plasmonic-Enhanced Solar Energy Harvest for Highly Efficient Photocatalytic Reactions. AB - We report a highly efficient photocatalyst comprised of Cu7S4@Pd heteronanostructures with plasmonic absorption in the near-infrared (NIR)-range. Our results indicated that the strong NIR plasmonic absorption of Cu7S4@Pd facilitated hot carrier transfer from Cu7S4 to Pd, which subsequently promoted the catalytic reactions on Pd metallic surface. We confirmed such enhancement mechanism could effectively boost the sunlight utilization in a wide range of photocatalytic reactions, including the Suzuki coupling reaction, hydrogenation of nitrobenzene, and oxidation of benzyl alcohol. Even under irradiation at 1500 nm with low power density (0.45 W/cm(2)), these heteronanostructures demonstrated excellent catalytic activities. Under solar illumination with power density as low as 40 mW/cm(2), nearly 80-100% of conversion was achieved within 2 h for all three types of organic reactions. Furthermore, recycling experiments showed the Cu7S4@Pd were stable and could retain their structures and high activity after five cycles. The reported synthetic protocol can be easily extended to other Cu7S4@M (M = Pt, Ag, Au) catalysts, offering a new solution to design and fabricate highly effective photocatalysts with broad material choices for efficient conversion of solar energy to chemical energy in an environmentally friendly manner. PMID- 26373789 TI - Gastrointestinal hormone secretion in women with polycystic ovary syndrome: an observational study. AB - STUDY QUESTION: Is the secretion of gastrointestinal hormones impaired in patients with polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: Gastrointestinal hormone levels were abnormal in patients with PCOS. WHAT IS KNOWN ALREADY: The hormones glucagon-like peptide-1 (GLP-1) and peptide tyrosine-tyrosine (PYY) are both involved in signaling satiety. Secretion of GLP-1 and PYY in response to nutrients in the small intestine plays an important role in energy metabolism. Most PCOS patients are overweight or obese, which suggests dysregulation of appetite. STUDY DESIGN, SIZE, DURATION: In order to evaluate levels of gastrointestinal hormones in PCOS, a cohort study was undertaken, involving 30 PCOS patients and 29 BMI-matched healthy women recruited from Shanghai Renji Hospital between 1 March 2013 and 30 May 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS: After an overnight fast, all participants underwent an oral glucose tolerance test. Blood was sampled frequently for measurement of blood glucose and plasma insulin, total GLP-1 and PYY concentrations. MAIN RESULTS AND THE ROLE OF CHANCE: Fasting and postprandial insulin levels were significantly higher in patients with PCOS compared with the healthy controls (P < 0.05). Fasting and postprandial GLP-1 (t = 0 and 30 min; mean +/- SEM) were also higher in PCOS group (17.5 +/- 1.07 pM versus 14.1 +/- 1.16 pM, P < 0.05; 29.7 +/- 2.39 pM versus 22.8 +/- 2.09 pM, P < 0.05). However, there were no differences in plasma PYY between patients with PCOS and healthy controls either fasting or postprandially. PYY levels were lower in obese PCOS patients than in lean PCOS patients (P < 0.05). LIMITATIONS, REASONS FOR CAUTION: The study involved a small number of subjects with PCOS, and examined hormone responses to oral glucose rather than a physiological meal. WIDER IMPLICATIONS OF THE FINDINGS: Deficient secretion of GLP-1 and PYY does not contribute to excessive food intake in the pathophysiology of PCOS. PMID- 26373788 TI - Ciliary function and motor protein composition of human fallopian tubes. AB - STUDY QUESTION: What is the motor protein composition and function of human fallopian tube (FT) cilia? SUMMARY ANSWER: Although the motor protein composition and function of human FT cilia resemble that of respiratory cilia, females with primary ciliary dyskinesia (PCD) are not necessarily infertile. WHAT IS KNOWN ALREADY: FTs are lined with multiple motile cilia, which show a 9 + 2 ultrastructure by transmission electron microscopy. Case reports suggest an increased incidence of subfertility and ectopic pregnancy in women with PCD, a disease characterized by dysfunction of motile cilia and flagella. STUDY DESIGN, SIZE, DURATION: This study consisted of an observational laboratory study on human FT specimens from five healthy females recruited from April 2012 to December 2013 and a descriptive observational retrospective analysis of a clinical PCD database. PARTICIPANTS/MATERIALS, SETTING, METHODS: Human FT tissue was obtained from five healthy females after tubal ligation during caesarean delivery. Motor protein composition was assessed by immunofluorescence microscopy using antibodies against dynein arms and nexin-dynein regulatory complex subunits. Ciliary motility was analysed by high-speed video microscopy. A retrospective search of our database of PCD individuals was performed for information on conception and childbirth. MAIN RESULTS AND THE ROLE OF CHANCE: The motor protein composition of human FT cilia was identical to that of respiratory cilia. FT cilia showed coordinated beating, resulting in a directed fluid flow towards the uterine cavity. We identified nine PCD individuals with severe dysfunction of respiratory cilia who gave birth to children after spontaneous conception. This suggests that ciliary beating is not the key motor of ovum transport. LIMITATIONS, REASON FOR CAUTION: FT cilia of affected PCD females were not available for analysis. Thus, it remains to be proven that FT cilia indeed show the same defects as respiratory cilia in PCD individuals. Comprehensive epidemiological studies are needed to determine the extent of female (sub-) fertility in PCD. WIDER IMPLICATIONS OF THE FINDINGS: Knowledge of the exact protein composition and function of FT cilia will contribute to a better understanding of cilia-generated fluid flow in female reproduction. These findings are important for subsequent studies of function and protein composition of FT cilia in PCD patients. PMID- 26373790 TI - Reduced breast cancer risk seen with Mediterranean diet and added olive oil. PMID- 26373791 TI - Divisibility patterns of natural numbers on a complex network. AB - Investigation of divisibility properties of natural numbers is one of the most important themes in the theory of numbers. Various tools have been developed over the centuries to discover and study the various patterns in the sequence of natural numbers in the context of divisibility. In the present paper, we study the divisibility of natural numbers using the framework of a growing complex network. In particular, using tools from the field of statistical inference, we show that the network is scale-free but has a non-stationary degree distribution. Along with this, we report a new kind of similarity pattern for the local clustering, which we call "stretching similarity", in this network. We also show that the various characteristics like average degree, global clustering coefficient and assortativity coefficient of the network vary smoothly with the size of the network. Using analytical arguments we estimate the asymptotic behavior of global clustering and average degree which is validated using numerical analysis. PMID- 26373792 TI - Bridged bis-BODIPYs: their synthesis, structures and properties. AB - A series of bis-BODIPYs 1-6 bridged via thiophene, furan, N-alkylcarbazole, triphenyl-amine, para- and meta-phenylene groups have been synthesized and characterized by various spectroscopic techniques. The change in the spectroscopic properties of bis-BODIPYs upon varying the size of spacers was studied. X-ray crystal structures of three bis-BODIPYs containing triphenylamine, para- and meta-phenylene bridges were solved. Intermolecular C(H)pi and pipi stacking interactions were observed in solid state structures of three bis BODIPYs. The dihedral angles between the spacer unit and two boron-dipyrrin units were lower in all three compounds as compared to their corresponding monomers. This suggests increased interactions between the two boron-dipyrrin units in molecules which are in turn reflected in the anodic shifts in their reduction potentials. DFT studies indicated effective electronic interactions between spacers and two boron dipyrrin units in all the bis-BODIPYs. The calculated HOMO LUMO gap was found to be lower for bis-BODIPY having bulky carbazole spacers and higher for bis-BODIPY having smaller furan spacers. Changing the spacer size clearly affected the spectroscopic properties of the bis-BODIPYs and red shifted absorption and emission maxima were observed for bis-BODIPYs with furan and thiophene spacers as compared to bis-BODIPYs with phenylene or bulky aromatic spacers. PMID- 26373793 TI - Phosphole formation by 1,1-carboboration--reactions of bis-alkynyl phosphanes with a frustrated P/B Lewis pair. AB - The arylbis(phenylethynyl)phosphanes 1a,b (aryl = mesityl, 2,4,6 triisopropylphenyl) react with the frustrated P/B Lewis pair (P/B FLP) mes2PCH2CH2B(C6F5)2 (4) to give mixtures of three products; the major products, the phosphole systems 2a,b, are formed by a sequence of 1,1-carboboration reactions. One of the minor compounds (6a,b) is formed by 1,1-carboboration followed by internal 1,2-FLP addition to the remaining C = C triple bond. The other minor compound of the product mixture (5a,b) is obtained by 1,2-FLP addition to one alkynyl moiety of the starting material. The products 5a, 6b and a derivative of the phosphole 2a (formed by FLP reaction with a terminal alkyne) were characterized by X-ray diffraction. The reaction of the arylbis(pentynyl)phosphanes 1c,d with the FLP 4 selectively gave the respective B(C6F5)2/-CH2CH2-Pmes2 substituted phospholes 2c,d which were isolated as orange solids in high yields. Rapid strongly temperature dependent equilibration between open and closed PB FLP isomers was detected for both systems by NMR spectroscopy. PMID- 26373794 TI - Polymorphism of IL37 gene as a protective factor for autoimmune thyroid disease. AB - Autoimmune thyroid disease (AITD) comprises Graves' disease (GD) and Hashimoto's thyroiditis (HT). IL37 has been recently proved to be a natural suppressor for innate immunity and acquired immunity. Therefore, this study was conducted to identify the association of IL37 genetic polymorphisms with AITD in Chinese Han population. Polymorphisms of rs3811046/rs3811047/rs2723176/rs272186 in the IL37 gene were assessed in a case-control study comprising 701 GD patients, 301 HT patients and 939 controls. Genetic variants were genotyped by multiplex polymerase chain reaction and ligase detection reaction. The frequencies of the minor allele A of rs2723176 and A of rs2723186 were significantly lower in the GD patients than in the controls (P=0.014, OR=0.774; P=0.014, OR=0.777). After gender stratification, the rs3811046 G allele and the rs3811047/rs2723186 A allele were both significantly associated with a decreased risk of GD in female patients (P=0.030, OR=0.777; P=0.023, OR=0.774; P=0.029, OR=0.761). However, none of the four single nucleotide polymorphisms of IL37 gene showed any significant association with HT. Moreover, haplotype analysis revealed the GCG haplotype conferred increased risk for GD as a whole and in female GD patients (OR=1.213; OR=1.320). The ACG haplotype was associated with an increased risk of HT as a whole (OR=1.567) and in male GD patients (OR=1.820). In contrast, the AAA haplotype showed a protective role for GD as a whole (OR=0.760) and in female GD patients (OR=0.765). Our study strongly supports that the IL37 gene variants are associated with the susceptibility to AITD. PMID- 26373795 TI - HC toxin (a HDAC inhibitor) enhances IRS1-Akt signalling and metabolism in mouse myotubes. AB - Exercise enhances numerous signalling pathways and activates substrate metabolism in skeletal muscle. Small molecule compounds that activate these cellular responses have been shown to recapitulate the metabolic benefits of exercise. In this study, a histone deacetylase (HDAC) inhibitor, HC toxin, was investigated as a small molecule compound that activates exercise-induced adaptations. In C2C12 myotubes, HC toxin treatment activated two exercise-stimulated pathways: AMP activated protein kinase (AMPK) and Akt pathways. HC toxin increased the protein content and phosphorylation of insulin receptor substrate 1 as well as the activation of downstream Akt signalling. The effects of HC toxin on IRS1-Akt signalling were PI3K-dependent as wortmannin abolishes its effects on IRS1 protein accumulation and Akt phosphorylation. HC toxin-induced Akt activation was sufficient to enhance downstream mTOR complex 1 (mTORC1) signalling including p70S6K and S6, which were consistently abolished by PI3K inhibition. Insulin stimulated glucose uptake, glycolysis, mitochondrial respiration and fatty acid oxidation were also enhanced in HC toxin-treated myotubes. When myotubes were challenged with serum starvation for the induction of atrophy, HC toxin treatment prevented the induction of genes that are involved in autophagy and proteasomal proteolysis. Conversely, IRS1-Akt signalling was not induced by HC toxin in several hepatoma cell lines, providing evidence for a favourable safety profile of this small molecule. These data highlight the potential of HDAC inhibitors as a novel class of small molecules for the induction of exercise-like signalling pathways and metabolism. PMID- 26373796 TI - Progranulin induces adipose insulin resistance and autophagic imbalance via TNFR1 in mice. AB - Progranulin (PGRN) has recently emerged as an important regulator for insulin resistance. However, the direct effect of PGRN in vivo and the underlying role of progranulin in adipose insulin resistance involving the autophagy mechanism is not fully understood. In this study, mice treated with PGRN for 21 days exhibited the impaired glucose tolerance and insulin sensitivity, remarkable adipose autophagy as well as attenuated insulin signaling via inhibition of mammalian target of rapamycin (mTOR) pathway. Furthermore, blockade of tumor necrosis factor receptor 1 (TNFR1) by TNFR1BP-Fc injection resulted in the restoration of impaired insulin sensitivity and insulin signaling induced by PGRN. Consistent with these findings in vivo, PGRN treatment induced defective insulin signaling, abnormal autophagic and mitochondrial activity in cultured adipocytes, while such effects were nullified by the blockade of TNFR1. In addition, PGRN-deficient adipocytes were more refractory to tunicamycin- or dexamethasone-induced insulin resistance, indicating the causative role of the TNFR1 pathway in the action of PGRN. Collectively, our findings support the notion that PGRN is a key regulator of insulin resistance and that PGRN may mediate its effects, at least in part, by inducing autophagy via the TNFR1-dependent mechanism. PMID- 26373797 TI - Detection of functional polymorphisms influencing the promoter activity of the SAA2 gene and their association with milk production traits in Chinese Holstein cows. AB - Our previous RNA sequencing experiment showed that the serum amyloid A2 (SAA2) gene was one of the most promising candidates for milk protein and fat traits in dairy cattle. The SAA2 gene encodes an apolipoprotein related to high-density lipoproteins. To further validate its genetic effects, genotype-phenotype associations were performed in this study. Through resequencing of the entire coding region and the 5'-regulatory region of the SAA2 gene using pooled DNA of 12 unrelated sires, one novel 3-bp insertion-deletion and five previously reported SNPs were detected. These identified SNPs were genotyped and tested for association with five milk production-related traits in 717 Chinese Holstein cows. After Bonferroni correction for multiple t-tests, five of them were found to be statistically significant for milk yield, fat yield and protein yield (P < 0.0001~0.0053). Haplotype-based association analysis revealed a similar effect on fat yield and protein yield (P = 0.0005, P = 0.0032 respectively). Then, using luciferase report assay, the regulatory effect of the three SNPs located in the promoter region (c.-22G>A; c.17G>C; c.114G>A) was evaluated on transcriptional activity. In HEK-293 cell lines, we found that constructs GCG and AGG showed higher luciferase activity compared with GCA (P < 0.01, P < 0.01 respectively). Meanwhile, the prediction of the putative differential transcription factor binding site revealed that c.17G>C and c.114G>A caused the alteration in the transcription factor. Overall, the findings presented here provide the first evidence for associations of the SAA2 gene with milk fat and protein traits, which appears to be a key candidate for milk production traits in dairy cattle. PMID- 26373800 TI - The RNA-binding protein Musashi 1 stabilizes the oncotachykinin 1 mRNA in breast cancer cells to promote cell growth. AB - Substance P and its truncated receptor exert oncogenic effects. The high production of substance P in breast cancer cells (BCCs) is caused by the enhancement of tachykinin (TAC)1 translation by cytosolic factor. In vitro translational studies and mRNA stabilization analyses indicate that BCCs contain the factor needed to increase TAC1 translation and to stabilize the mRNA. Prediction of protein folding, RNA-shift analysis, and proteomic analysis identified a 40 kDa molecule that interacts with the noncoding exon 7. Western blot analysis and RNA supershift identified Musashi 1 (Msi1) as the binding protein. Ectopic expression of TAC1 in nontumorigenic breast cells (BCs) indicates that TAC1 regulates its stability by increasing Msi1. Using a reporter gene system, we showed that Msi1 competes with microRNA (miR)130a and -206 for the 3' UTR of exon 7/TAC1. In the absence of Msi1 and miR130a and -206, reporter gene activity decreased, indicating that Msi1 expression limits TAC1 expression. Tumor growth was significantly decreased when nude BALB/c mice were injected with Msi1-knockdown BCCs. In summary, the RNA-binding protein Msi1 competes with miR130a and -206 for interaction with TAC1 mRNA, to stabilize and increase its translation. Consequently, these interactions increase tumor growth. PMID- 26373801 TI - Canonical transient receptor potential 3 channels activate NF-kappaB to mediate allergic airway disease via PKC-alpha/IkappaB-alpha and calcineurin/IkappaB-beta pathways. AB - The purpose of this study was to determine the role of canonical transient receptor potential 3 (TRPC3) channel in allergen-induced airway disease (AIAD) and its underlying signaling mechanisms. The procedures included (1) intravenous injection of lentiviral TRPC3 channel or nonsilencing short hairpin ribonucleic acid (shRNA) to make the channel knockdown (KD) or control mice, (2) allergen sensitization/challenge to induce AIAD, (3) patch-clamp recording and Ca(2+) imaging to examine the channel activity, and (4) gene manipulations and other methods to determine the underlying signaling mechanisms. The findings are that (1) intravenous or intranasal delivery of TRPC3 channel lentiviral shRNAs or blocker 1-[4-[(2,3,3-trichloro-1-oxo-2-propen-1-yl)amino]phenyl]-5 (trifluoromethyl)-1H-pyrazole-4-carboxylic acid prevents AIAD in mice, (2) TRPC3 channel KD and overexpression, respectively, blocks and augments protein kinase C alpha/nuclear factor of kappa light polypeptide gene enhancer in B-cell inhibitor alpha (PKC-alpha/IkappaB-alpha)-mediated or calcineurin/IkappaB-beta-dependent, NF-kappaB-dependent allergen-induced airway smooth muscle cell (ASMC) hyperproliferation and cyclin D1 (an important cell proliferation molecule) induction, and (3) the changes of the major molecules of the PKC alpha/IkappaBalpha- and calcineurin/IkappaB-beta-dependent NF-kappaB signaling pathways are also observed in asthmatic human ASMCs. The conclusions are that TRPC3 channels plays an essential role in AIAD via the PKC-alpha/IkappaB-alpha- and calcineurin/IkappaB-beta-dependent NF-kappaB signaling pathways, and lentiviral shRNA or inhibitor of TRPC3 channels may become novel and effective treatments for AIAD. PMID- 26373802 TI - Membrane and nuclear estrogen receptor alpha collaborate to suppress adipogenesis but not triglyceride content. AB - Estrogen and estrogen receptor (ER)-alpha suppress visceral fat development through actions in several organs via unclear mechanisms that we sought to identify. Using mice that express only nuclear ER-alpha [nuclear-only ER-alpha (NOER) mice] or plasma membrane ER-alpha [membrane-only ER-alpha (MOER) mice], we found that 10-wk-old mice that lacked either receptor pool showed extensive abdominal visceral fat deposition and weight gain compared with wild-type (WT) mice. Differentiation of cultured bone marrow stem cells (BMSCs) into the adipocyte lineage was suppressed by 17-beta-estradiol (E2) in WT female mice but not in NOER or MOER mice. This finding correlated with E2 inhibition of prominent differentiation genes in WT BMSCs. In contrast, triglyceride content in differentiated BMSCs or 3T3-L1 cells was suppressed as a result of membrane ER alpha signaling through several kinases to inhibit carbohydrate response element binding protein-alpha and -beta. We concluded that extranuclear and nuclear ER alpha collaborate to suppress adipocyte development, but inhibition of lipid synthesis in mature cells does not involve nuclear ER-alpha. PMID- 26373803 TI - Recovery trajectories of kelp forest animals are rapid yet spatially variable across a network of temperate marine protected areas. AB - Oceans currently face a variety of threats, requiring ecosystem-based approaches to management such as networks of marine protected areas (MPAs). We evaluated changes in fish biomass on temperate rocky reefs over the decade following implementation of a network of MPAs in the northern Channel Islands, California. We found that the biomass of targeted (i.e. fished) species has increased consistently inside all MPAs in the network, with an effect of geography on the strength of the response. More interesting, biomass of targeted fish species also increased outside MPAs, although only 27% as rapidly as in the protected areas, indicating that redistribution of fishing effort has not severely affected unprotected populations. Whether the increase outside of MPAs is due to changes in fishing pressure, fisheries management actions, adult spillover, favorable environmental conditions, or a combination of all four remains unknown. We evaluated methods of controlling for biogeographic or environmental variation across networks of protected areas and found similar performance of models incorporating empirical sea surface temperature versus a simple geographic blocking term based on assemblage structure. The patterns observed are promising indicators of the success of this network, but more work is needed to understand how ecological and physical contexts affect MPA performance. PMID- 26373805 TI - Interrelationships between indices of longitudinal movement of the common carotid artery wall and the conventional measures of subclinical arteriosclerosis. AB - Our objective was to study the interrelationships between longitudinal movement of the wall of the common carotid artery and the conventional measures of arteriosclerosis in a large and well-characterized study population. Successful longitudinal movement analyses were performed on 292 subjects. The peak-to-peak and retrograde amplitudes of the longitudinal movement were directly correlated with carotid artery distensibility (r = 0.21, P<0.001 and r = 0.23, P<0.001, respectively) and inversely correlated with pulse wave velocity (r = -0.14, P<0.05 and r = -0.17, P<0.01, respectively). All longitudinal motion parameters were independent of brachial flow-mediated dilatation and intima-media thickness. Our findings indicate that arterial stiffening modulates longitudinal movement and, therefore, measurement of longitudinal movement can be of value in the assessment of vascular health. PMID- 26373806 TI - High diversity and rapid diversification in the head louse, Pediculus humanus (Pediculidae: Phthiraptera). AB - The study analyzes sequence variation of two mitochondrial genes (COI, cytb) in Pediculus humanus from three countries (Egypt, Pakistan, South Africa) that have received little prior attention, and integrates these results with prior data. Analysis indicates a maximum K2P distance of 10.3% among 960 COI sequences and 13.8% among 479 cytb sequences. Three analytical methods (BIN, PTP, ABGD) reveal five concordant OTUs for COI and cytb. Neighbor-Joining analysis of the COI sequences confirm five clusters; three corresponding to previously recognized mitochondrial clades A, B, C and two new clades, "D" and "E", showing 2.3% and 2.8% divergence from their nearest neighbors (NN). Cytb data corroborate five clusters showing that clades "D" and "E" are both 4.6% divergent from their respective NN clades. Phylogenetic analysis supports the monophyly of all clusters recovered by NJ analysis. Divergence time estimates suggest that the earliest split of P. humanus clades occurred slightly more than one million years ago (MYa) and the latest about 0.3 MYa. Sequence divergences in COI and cytb among the five clades of P. humanus are 10X those in their human host, a difference that likely reflects both rate acceleration and the acquisition of lice clades from several archaic hominid lineages. PMID- 26373807 TI - Genetic mapping uncovers cis-regulatory landscape of RNA editing. AB - Adenosine-to-inosine (A-to-I) RNA editing, catalysed by ADAR enzymes conserved in metazoans, plays an important role in neurological functions. Although the fine tuning mechanism provided by A-to-I RNA editing is important, the underlying rules governing ADAR substrate recognition are not well understood. We apply a quantitative trait loci (QTL) mapping approach to identify genetic variants associated with variability in RNA editing. With very accurate measurement of RNA editing levels at 789 sites in 131 Drosophila melanogaster strains, here we identify 545 editing QTLs (edQTLs) associated with differences in RNA editing. We demonstrate that many edQTLs can act through changes in the local secondary structure for edited dsRNAs. Furthermore, we find that edQTLs located outside of the edited dsRNA duplex are enriched in secondary structure, suggesting that distal dsRNA structure beyond the editing site duplex affects RNA editing efficiency. Our work will facilitate the understanding of the cis-regulatory code of RNA editing. PMID- 26373808 TI - Frequent activation of the beta-catenin gene in sporadic colorectal carcinomas: A mutational & expression analysis. AB - beta-catenin (CTNNB1), an oncogene/onco-protein and an adhesion molecule is a key effector in colorectal cancer (CRC). Its activation, and subsequent up-regulation of Wnt-signaling, is an important event in the development of certain human cancers including CRC. Mutations in the beta-catenin gene in the region of serine threonine glycogen kinase (GSK)-3beta phosphorylation target sites have been identified in colorectal cancer in humans. In the current study, we investigated 60 sporadic colorectal adenocarcinomas along with adjoining and normal mucosa cases in humans for beta-catenin mutations. Thirteen of sixty colorectal tumors from humans had point mutations with a frequency of 21.66% at codons 24, 26, 27, 32, 34, 35, 41, 42,43, 46, 49, 54, 55, or 67 sites which are mutated in colorectal cancer and some of these sites in other cancers. Thus, there appears to be a key involvement of beta-catenin activation in human colorectal carcinogenesis. mRNA expression analysis using q-Real Time PCR showed 21.5-fold up-regulation of beta-catenin mRNA in tumor tissue compared to normal and adjoining mucosa. Protein expression analysis using immunohistochemistry, confocal microscopy, and Western blot confirmed aberrant accumulation of beta catenin protein along the nucleus and cytoplasm following mutation. The observed mutations and up-regulation of mRNA in tumors, and the increased expression of beta-catenin protein in CRC suggest that these alterations are early and prognostic events in sporadic colorectal carcinogenesis in humans. (c) 2015 Wiley Periodicals, Inc. PMID- 26373809 TI - Letter to the Editor regarding triggering of acute coronary occlusion by episodes of anger. PMID- 26373810 TI - Role of intra-aortic balloon pump counterpulsation in the treatment of acute myocardial infarction complicated by cardiogenic shock: Evidence from the Portuguese nationwide registry. AB - BACKGROUND: In previous guidelines, intra-aortic balloon pump (IABP) use was strongly recommended in the treatment of cardiogenic shock in the context of acute myocardial infarction. The recent IABP-SHOCK II trial demonstrated no benefit in short- and medium-term mortality with the use of IABP. It was our objective to evaluate in a real life nationwide population of patients with acute myocardial infarction the impact of IABP in short- and medium-term mortality. METHODS: We included patients admitted with acute myocardial infarction in Killip class IV in the first 24 hours, all submitted to urgent coronary angiography. Our study objective was the occurrence of hospital and six-month all-cause mortality. RESULTS: From the 33,300 patients included in the registry, 4.2% presented with Killip class IV in the first 24 hours and 646 (43.6%) were submitted to urgent coronary angiography. IABP was implanted in 19.8% of these patients. The IABP group was younger, had higher admission heart rate, more multivessel disease and more left main disease. There were 260 hospital deaths (40.2%), similar between groups (46.1% vs. 38.8%, p=0.132). IABP use was associated with a deleterious effect in patients with previous MI and beneficial effect in patients with mechanical complications. IABP use had a neutral effect on mortality (hazard ratio 1.14, 95% confidence interval 0.84-1.56). This was further confirmed in a propensity score matching analysis. CONCLUSIONS: In a real life population of patients with acute myocardial infarction, the use of IABP for the treatment of cardiogenic shock was associated with a neutral effect. PMID- 26373811 TI - ST-segment elevation in V1-V4 in acute pulmonary embolism: a case presentation and review of literature. AB - INTRODUCTION: Electrocardiographic (ECG) abnormalities are seen in 70%-80% of patients with acute pulmonary embolism (APE). Rarely, APE presents with ST segment elevation (STE) in leads V1-V4, mimicking ST-segment elevation myocardial infarction (STEMI). Herein, we describe a case of APE presenting with STE in V1 V3, along with a comprehensive review of the literature. METHODS: We reviewed Pubmed/Medline indexed articles from 1950 to 2014 reporting cases of APE presenting with STE in V1-V3 or V4 (V1-V3/V4). Cases were analyzed with specific reference to patient demographics, clinical, laboratory, and radiological data, treatment, and outcome. RESULTS: A total of 12 cases were identified comprising seven males and five females aged between 31 and 64 years. Five cases met the American College of Cardiology/American Heart Association criteria for massive APE due to sustained hemodynamic instability or requirement for inotropic support, and seven met criteria for submassive PE due to right ventricular (RV) dysfunction or elevated troponin in absence of systemic hypotension. Among the notable clinical features in this cohort is the high incidence of syncope, in 66.7% of the cases, high incidence of concomitant deep venous thrombosis (DVT) in 90% of cases that reported venous Doppler results (eight proximal and one distal DVT), and the presence of a dilated RV in 90% of the cases that reported echocardiographic results. In all but one case the initial working diagnosis was STEMI and emergent cardiac catheterization was planned. In the 90% of cases who eventually had a coronary angiography, the angiogram was performed prior to diagnosing APE, and the lack of occlusive disease prompted further workup that confirmed the diagnosis of APE. In-hospital mortality rate in the studied population was 16.7%. CONCLUSION: STE in leads V1-V3/V4 in cases with APE identifies a subset of patients who are an intermediate to high risk category. In cases presenting with right precordial lead STE and clinical features that are more suggestive of APE rather than STEMI, a computed tomography pulmonary angiogram is warranted for earlier diagnosis of suspected APE, which allow for immediate-rather than delayed-initiation of therapeutic anticoagulant therapy if the diagnosis is confirmed and may avert the need for coronary angiography. PMID- 26373812 TI - Pharyngeal pouch management: an historical review. AB - BACKGROUND: Management of the pharyngeal pouch has evolved enormously since the first description by Ludlow in 1764 and the first case series by Zenker and Von Ziemssen in 1877. With the introduction of antibiotics, and the advancement of surgical technique with the advent of endoscopic surgery and lasers, current management is vastly different to that in the nineteenth century. OBJECTIVES: This paper traces the history of pharyngeal pouch management, and discusses the various treatment options and opinions recorded during the nineteenth and twentieth centuries, comparing these with techniques popular today. RESULTS AND CONCLUSION: Pharyngeal pouch surgery has been associated with significant morbidity, both because of the elderly age of patients typically affected by the condition and because of the surgery itself and potential post-operative complications encountered. The historical development of pharyngeal pouch management and the understanding of pharyngeal pouch pathophysiology are discussed. PMID- 26373815 TI - Clinical Research Abstracts of the British Equine Veterinary Association Congress 2014. PMID- 26373813 TI - Differential Contributions of Alcohol and Nicotine-Derived Nitrosamine Ketone (NNK) to White Matter Pathology in the Adolescent Rat Brain. AB - AIM: Epidemiologic studies have demonstrated high rates of smoking among alcoholics, and neuroimaging studies have detected white matter atrophy and degeneration in both smokers and individuals with alcohol-related brain disease (ARBD). These findings suggest that tobacco smoke exposure may be a co-factor in ARBD. The present study examines the differential and additive effects of tobacco specific nitrosamine (NNK) and ethanol exposures on the structural and functional integrity of white matter in an experimental model. METHODS: Adolescent Long Evans rats were fed liquid diets containing 0 or 26% ethanol for 8 weeks. In weeks 3-8, rats were treated with nicotine-derived nitrosamine ketone (NNK) (2 mg/kg, 3*/week) or saline by i.p. injection. In weeks 7-8, the ethanol group was binge-administered ethanol (2 g/kg; 3*/week). RESULTS: Ethanol, NNK and ethanol + NNK caused striking degenerative abnormalities in white matter myelin and axons, with accompanying reductions in myelin-associated glycoprotein expression. Quantitative RT-PCR targeted array and heatmap analyses demonstrated that ethanol modestly increased, whereas ethanol + NNK sharply increased expression of immature and mature oligodendroglial genes, and that NNK increased immature but inhibited mature oligodendroglial genes. In addition, NNK modulated expression of neuroglial genes in favor of growth cone collapse and synaptic disconnection. Ethanol- and NNK-associated increases in FOXO1, FOXO4 and NKX2-2 transcription factor gene expression could reflect compensatory responses to brain insulin resistance in this model. CONCLUSION: Alcohol and tobacco exposures promote ARBD by impairing myelin synthesis, maturation and integrity via distinct but overlapping mechanisms. Public health measures to reduce ARBD should target both alcohol and tobacco abuses. PMID- 26373816 TI - Abstracts of the 49. Wissenschaftliche Tagung der Deutschsprachigen Mykologischen Gesellschaft e.V. and 1(st) International Symposium of the CRC/Transregio FungiNet, 16-19 September 2015, Friedrich-Schiller-Universitat Jena, Germany. PMID- 26373814 TI - Differential Contributions of Alcohol and the Nicotine-Derived Nitrosamine Ketone (NNK) to Insulin and Insulin-Like Growth Factor Resistance in the Adolescent Rat Brain. AB - AIMS: Since epidemiologic studies suggest that tobacco smoke toxins, e.g. the nicotine-derived nitrosamine ketone (NNK) tobacco-specific nitrosamine, can be a co-factor in alcohol-related brain disease (ARBD), we examined the independent and additive effects of alcohol and NNK exposures on spatial learning/memory, and brain insulin/IGF signaling, neuronal function and oxidative stress. METHODS: Adolescent Long Evans rats were fed liquid diets containing 0 or 26% caloric ethanol for 8 weeks. During weeks 3-8, rats were treated with i.p. NNK (2 mg/kg, 3*/week) or saline. In weeks 7-8, ethanol groups were binge-administered ethanol (2 g/kg; 3*/week). In week 8, at 12 weeks of age, rats were subjected to Morris Water Maze tests. Temporal lobes were used to assess molecular indices of insulin/IGF resistance, oxidative stress and neuronal function. RESULTS: Ethanol and NNK impaired spatial learning, and NNK +/- ethanol impaired memory. Linear trend analysis demonstrated worsening performance from control to ethanol, to NNK, and then ethanol + NNK. Ethanol +/- NNK, caused brain atrophy, inhibited insulin signaling through the insulin receptor and Akt, activated GSK-3beta, increased protein carbonyl and 3-nitrotyrosine, and reduced acetylcholinesterase. NNK increased NTyr. Ethanol + NNK had synergistic stimulatory effects on 8-iso PGF-2alpha, inhibitory effects on p-p70S6K, tau and p-tau and trend effects on insulin-like growth factor type 1 (IGF-1) receptor expression and phosphorylation. CONCLUSIONS: Ethanol, NNK and combined ethanol + NNK exposures that begin in adolescence impair spatial learning and memory in young adults. The ethanol and/or NNK exposures differentially impair insulin/IGF signaling through neuronal growth, survival and plasticity pathways, increase cellular injury and oxidative stress and reduce expression of critical proteins needed for neuronal function. PMID- 26373817 TI - Unusually Large Young's Moduli of Amino Acid Molecular Crystals. AB - Young's moduli of selected amino acid molecular crystals were studied both experimentally and computationally using nanoindentation and dispersion-corrected density functional theory. The Young modulus is found to be strongly facet dependent, with some facets exhibiting exceptionally high values (as large as 44 GPa). The magnitude of Young's modulus is strongly correlated with the relative orientation between the underlying hydrogen-bonding network and the measured facet. Furthermore, we show computationally that the Young modulus can be as large as 70-90 GPa if facets perpendicular to the primary direction of the hydrogen-bonding network can be stabilized. This value is remarkably high for a molecular solid and suggests the design of hydrogen-bond networks as a route for rational design of ultra-stiff molecular solids. PMID- 26373818 TI - Minor anomalies in stillborn and second trimester miscarried fetuses. AB - In 1964, the landmark paper of Marden, Smith, and McDonald established that multiple minor anomalies in newborn infants are associated with an increased risk for major malformations. There were until now no comparable studies in stillbirths. The Wisconsin Stillbirth Service Program (WiSSP) has data regarding nearly 3,000 stillbirths and second trimester losses that have been analyzed for major anomalies and cause of death. One dysmorphologist retrospectively reviewed all 2,397 with usable photographs. Minor anomalies were identified in 1,413 (59%) with 575 of these (41%) having at least one major anomaly. Probability of a major anomaly increased from 7% with no minor anomalies to 15%, 36%, 67%, and 89% with 1, 2, 3, and >33 minor anomalies, respectively. Frequency of minor anomalies was less with lower resolution photographs, but did not show significant differences with maceration or gestational age. The most frequent minor anomalies were infraorbital creases/folds, lowset/posteriorly angulated ears, nuchal edema, flat face, equinovarus foot, camptodactyly, upslanted palpebral fissures, ear antihelix abnormalities (combined), micrognathia/retrognathia, and single transverse palmar crease. Except for infraorbital creases/folds each of these minor anomalies was strongly correlated with major anomalies (P < 0.0001). Infraorbital folds were the only anomaly which increased with placental cause of death, and reanalysis with placental causes excluded showed the expected relationship to major anomalies, suggesting that infraorbital folds may be markers for oligohydramnios due to various causes including placental hypoperfusion. Minor anomalies correlate with presence of major anomalies in stillborn fetuses, regardless of gestational age and maceration, and can provide information to guide decisions regarding laboratory testing and other evaluations. PMID- 26373819 TI - Divergent Roles of PAX2 in the Etiology and Progression of Ovarian Cancer. AB - PAX2 is an essential transcription factor for development. Aberrant PAX2 expression in adult tissues is associated with carcinogenesis and experimental evidence shows that PAX2 generally exhibits oncogenic properties. Although PAX2 is not expressed in normal ovaries, it is highly expressed in low malignant potential and low-grade epithelial ovarian tumors, suggesting that PAX2 induction in ovarian surface epithelium (OSE) may contribute to transformation. Herein, we provide evidence that expression of PAX2 in normal murine OSE cells (mOSE) enhances their proliferation and survival and, with loss of p53, induces tumorigenicity. PAX2 expression in murine ovarian cancer cells enhanced or inhibited tumorigenicity, depending on the model system. In RM cells (mOSE transformed by K-RAS and c-MYC), PAX2 expression inhibited p53 and induced pERK1/2 and COX2, resulting in enhanced angiogenesis and decreased apoptosis of tumors arising from these cells. However, in a murine model of high-grade serous ovarian cancer (STOSE), PAX2 expression improved animal survival by reducing proliferation and metastasis, which correlated with increased Htra1 and decreased COX2. Thus, PAX2 may not be a classical oncogene or tumor suppressor but instead can act in either role by differential regulation of COX2 and/or HTRA1. PMID- 26373820 TI - Effects of Nanotexture on Electrical Profiling of Single Tumor Cell and Detection of Cancer from Blood in Microfluidic Channels. AB - Microfluidic channels have been implemented to detect cancer cells from blood using electrical measurement of each single cell from the sample. Every cell provided characteristic current profile based on its mechano-physical properties. Cancer cells not only showed higher translocation time and peak amplitude compared to blood cells, their pulse shape was also distinctively different. Prevalent microfluidic channels are plain but we created nanotexture on the channel walls using micro reactive ion etching (micro-RIE). The translocation behaviors of the metastatic renal cancer cells through plain and nanotextured PDMS microchannels showed clear differences. Nanotexture enhanced the cell surface interactions and more than 50% tumor cells exhibited slower translocation through nanotextured channels compared to plain devices. On the other hand, most of the blood cells had very similar characteristics in both channels. Only 7.63% blood cells had slower translocation in nanotextured microchannels. The tumor cell detection efficiency from whole blood increased by 14% in nanotextured microchannels compared to plain channels. This interesting effect of nanotexture on translocation behavior of tumor cells is important for the early detection of cancer. PMID- 26373821 TI - The importance of molecular markers for diagnosis and selection of targeted treatments in patients with cancer. AB - The past 30 years have seen the introduction of a number of cancer therapies with the aim of restricting the growth and spread of primary and metastatic tumours. A shared commonality among these therapies is their targeting of various aspects of the cancer hallmarks, that is traits that are essential to successful tumour propagation and dissemination. The evolution of molecular-scale technology has been central to the identification of new cancer targets, and it is not a coincidence that improved therapies have emerged at the same time as gene expression arrays and DNA sequencing have enhanced our understanding of cancer genetics. Modern tumour pathology is now viewed at the molecular level ranging from IHC biomarkers, to gene signature classifiers and gene mutations, all of which provide crucial information about which patients will respond to targeted therapy regimens. In this review, we briefly discuss the general types of targeted therapies used in a clinical setting and provide a short background on immunohistochemical, gene expression and DNA sequencing technologies, before focusing on three tumour types: breast, lung and colorectal cancers. For each of these cancer types, we provide a background to the disease along with an overview of the current standard therapies and then focus on the relevant targeted therapies and the pathways they inhibit. Finally, we highlight several strategies that are pivotal to the successful development of targeted anti-cancer drugs. PMID- 26373822 TI - GLUT4 translocation is not impaired after acute exercise in skeletal muscle of women with obesity and polycystic ovary syndrome. AB - OBJECTIVE: The aim of this study was to examine the effects of acute exercise on insulin signaling in skeletal muscle of women with polycystic ovary syndrome (PCOS) and controls (CTRL). METHODS: Fifteen women with obesity and PCOS and 12 body mass index-matched CTRL participated in this study. Subjects performed a 40 min single bout of exercise. Muscle biopsies were performed before and 60 min after exercise. Selected proteins were assessed by Western blotting. RESULTS: CTRL, but not PCOS, showed a significant increase in PI3-k p85 and AS160 Thr 642 after a single bout of exercise (P = 0.018 and P = 0.018, respectively). Only PCOS showed an increase in Akt Thr 308 and AMPK phosphorylation after exercise (P = 0.018 and P = 0.018, respectively). Total GLUT4 expression was comparable between groups (P > 0.05). GLUT4 translocation tended to be significantly higher in both groups after exercise (PCOS: P = 0.093; CTRL: P = 0.091), with no significant difference between them (P > 0.05). CONCLUSIONS: A single bout of exercise elicited similar GLUT4 translocation in skeletal muscle of PCOS and CTRL, despite a slightly differential pattern of protein phosphorylation. The absence of impairment in GLUT4 translocation suggests that PCOS patients with obesity and insulin resistance may benefit from exercise training. PMID- 26373823 TI - Surveillance of parasitic Legionella in surface waters by using immunomagnetic separation and amoebae enrichment. AB - Free-living amoebae (FLA) are potential reservoirs of Legionella in aquatic environments. However, the parasitic relationship between various Legionella and amoebae remains unclear. In this study, surface water samples were gathered from two rivers for evaluating parasitic Legionella. Warmer water temperature is critical to the existence of Legionella. This result suggests that amoebae may be helpful in maintaining Legionella in natural environments because warmer temperatures could enhance parasitisation of Legionella in amoebae. We next used immunomagnetic separation (IMS) to identify extracellular Legionella and remove most free Legionella before detecting the parasitic ones in selectively enriched amoebae. Legionella pneumophila was detected in all the approaches, confirming that the pathogen is a facultative amoebae parasite. By contrast, two obligate amoebae parasites, Legionella-like amoebal pathogens (LLAPs) 8 and 9, were detected only in enriched amoebae. However, several uncultured Legionella were detected only in the extracellular samples. Because the presence of potential hosts, namely Vermamoeba vermiformis, Acanthamoeba spp. and Naegleria gruberi, was confirmed in the samples that contained intracellular Legionella, uncultured Legionella may survive independently of amoebae. Immunomagnetic separation and amoebae enrichment may have referential value for detecting parasitic Legionella in surface waters. PMID- 26373825 TI - Raloxifene nanomicelles reduce the growth of castrate-resistant prostate cancer. AB - BACKGROUND: Castrate-resistant prostate cancer (CRPC) patients are characterised by a 5-year relative survival rate of ~25-33%. Recently, our laboratory encapsulated a selective oestrogen receptor modulator, raloxifene, into poly(styrene-co-maleic acid) (SMA-raloxifene), which demonstrated superior in vitro cytotoxicity compared with free drug against several CRPC cell lines. PURPOSE: To validate SMA-raloxifene for the management of CRPC using a mouse xenograft model. METHODS: The internalisation and retention of micellar and free raloxifene in vitro were measured by HPLC. A PC3-CRPC xenograft model was used to compare the biodistribution of both raloxifene formulations, as well as their effect on tumour progression where mice received free raloxifene (1 or 5 mg/kg, i.v.) or SMA-raloxifene (1 mg/kg, i.v.) weekly for 4 weeks. RESULTS: SMA raloxifene exhibited 75% higher intracellular content compared to free drug after 48 h in PC3 cells. Biodistribution of raloxifene was 69% higher in tumours following SMA-raloxifene compared with free raloxifene. Weekly administration of 1 mg/kg free raloxifene reduced tumour progression by 20% after 4 weeks, whereas 1 mg/kg SMA-raloxifene and 5 mg/kg free raloxifene reduced progression by 40%. CONCLUSION: Encapsulation of raloxifene increased its therapeutic potential for the management of CRPC. PMID- 26373826 TI - Agreement between Pleth Variability Index and oesophageal Doppler to predict fluid responsiveness. AB - BACKGROUND: Optimisation of stroke volume using oesophageal Doppler is an established technique to guide intraoperative fluid therapy. The method has practical limitations and therefore alternative indices of fluid responsiveness, such as ventilator-induced variation in the pulse oximetric signal (Pleth Variability Index (PVI)) could be considered. We hypothesised that both methods predict fluid responsiveness in a similar way. METHODS: Seventy-five patients scheduled for open major abdominal surgery were randomised to fluid optimisation using fluid bolus algorithms based on either PVI (n = 35) or Doppler (n = 39). All patients were monitored with both methods; the non-guiding method was blind. Primary endpoint was the concordance between the methods to predict fluid responsiveness. We also analysed the ability of each method to predict a stroke volume increase >= 10% after a fluid bolus, as well as the accumulated intraoperative bolus fluid volume. RESULTS: PVI indicated a need for fluid in one third of the situations when Doppler did so, Cohen's kappa = 0.03. A fluid bolus indicated by the PVI algorithm increased stroke volume by >= 10% in half the situations. The same was found for the Doppler algorithm. The mean total bolus volume given was 878 ml when the fluid management was governed by PVI compared to 826 ml with Doppler (P = 0.71). CONCLUSION: PVI- and Doppler-based stroke volume optimisations agreed poorly, which did not affect the amount of fluid administered. None of the algorithms showed a good ability to predict fluid responsiveness. Our results do not support the fluid responsiveness concept. PMID- 26373827 TI - Erratum to: Exposure to high concentrations of inspired oxygen does not worsen lung injury after cardiac arrest. PMID- 26373828 TI - Norepinephrine triggers metaplasticity of LTP by increasing translation of specific mRNAs. AB - Norepinephrine (NE) is a key modulator of synaptic plasticity in the hippocampus, a brain structure crucially involved in memory formation. NE boosts synaptic plasticity mostly through initiation of signaling cascades downstream from beta (beta)-adrenergic receptors (beta-ARs). Previous studies demonstrated that a beta adrenergic receptor agonist, isoproterenol, can modify the threshold for long term potentiation (LTP), a putative cellular mechanism for learning and memory, in a process known as "metaplasticity." Metaplasticity is the ability of synaptic plasticity to be modified by prior experience. We asked whether NE itself could engage metaplastic mechanisms in area CA1 of mouse hippocampal slices. Using extracellular field potential recording and stimulation, we show that application of NE (10 uM), which did not alter basal synaptic strength, enhances the future maintenance of LTP elicited by subthreshold, high-frequency stimulation (HFS: 1 * 100 Hz, 1 sec). HFS applied 30 min after NE washout induced long-lasting (>4 h) LTP, which was significantly extended in duration relative to HFS alone. This NE induced metaplasticity required beta1-AR activation, as coapplication of the beta1-receptor antagonist CGP-20712A (1 uM) attenuated maintenance of LTP. We also found that NE-mediated metaplasticity was translation- and transcription dependent. Polysomal profiles of CA1 revealed increased translation rates for specific mRNAs during NE-induced metaplasticity. Thus, activation of beta-ARs by NE primes synapses for future long-lasting plasticity on time scales extending beyond fast synaptic transmission; this may facilitate neural information processing and the subsequent formation of lasting memories. PMID- 26373829 TI - Infralimbic prefrontal cortex interacts with nucleus accumbens shell to unmask expression of outcome-selective Pavlovian-to-instrumental transfer. AB - Although several studies have examined the subcortical circuitry underlying Pavlovian-to-instrumental transfer (PIT), the role of medial prefrontal cortex in this behavior is largely unknown. Elucidating the cortical contributions to PIT will be key for understanding how reward-paired cues control behavior in both adaptive and maladaptive context (i.e., addiction). Here we use bilateral lesions in a rat model to show that infralimbic prefrontal cortex (ilPFC) is necessary for appropriate expression of PIT. Further, we show that ilPFC mediates this effect via functional connectivity with nucleus accumbens shell (NAcS). Together, these data provide the first demonstration that a specific cortico-striatal circuit is necessary for cue-invigorated reward seeking during specific PIT. PMID- 26373830 TI - Histone deacetylase inhibition facilitates massed pattern-induced synaptic plasticity and memory. AB - Massed training is less effective for long-term memory formation than the spaced training. The role of acetylation in synaptic plasticity and memory is now well established. However, the role of this important protein modification in synaptic plasticity induced by massed pattern of stimulation or memory induced by massed training is not well understood. Here we show that increasing the level of acetylation enhances long-term potentiation induced by massed pattern of high frequency stimulation. Furthermore, enhancing acetylation level facilitates long term memory by massed training. Thus, increasing acetylation level facilitates synaptic plasticity and memory by massed patterns. PMID- 26373831 TI - False context fear memory in rats. AB - Four experiments used rats to study false context fear memories. In Experiment 1, rats were pre-exposed to a distinctive chamber (context A) or to a control environment (context C), shocked after a delay in a second chamber (context B) and tested either in B or A. Rats pre-exposed to A froze just as much as control rats in B but more than control rats in A. In Experiment 2, rats were pre-exposed to A or C, subjected to an immediate shock in B and tested in B or A. Rats pre exposed to A froze when tested in A but did not freeze when tested in B and control rats did not freeze in either A or B. The false fear memory to the pre exposed A was contingent on its similarity with the shocked B. In Experiment 3, rats pre-exposed to A and subjected to immediate shock in B froze when tested in A but did not freeze when tested in C and rats pre-exposed to C did not freeze when tested either in A or C. In Experiment 4, rats pre-exposed to A and subjected to immediate shock in B froze more when tested in A than rats whose pre exposure to A began with an immediate shock. The results were discussed in terms of a dual systems explanation of context fear conditioning: a hippocampal dependent process that forms a unitary representation of context and an amygdala based process which associates this representation with shock. PMID- 26373832 TI - Corrigendum: Cholinergic manipulations bidirectionally regulate object memory destabilization. PMID- 26373833 TI - Transient relay function of midline thalamic nuclei during long-term memory consolidation in humans. AB - To test the hypothesis that thalamic midline nuclei play a transient role in memory consolidation, we reanalyzed a prospective functional MRI study, contrasting recent and progressively more remote memory retrieval. We revealed a transient thalamic connectivity increase with the hippocampus, the medial prefrontal cortex (mPFC), and a parahippocampal area, which decreased with time. In turn, mPFC-parahippocampal connectivity increased progressively. These findings support a model in which thalamic midline nuclei serve as a hub linking hippocampus, mPFC, and posterior representational areas during memory retrieval at an early (2 h) stage of consolidation, extending classical systems consolidation models by attributing a transient role to midline thalamic nuclei. PMID- 26373834 TI - Sleep enhances a spatially mediated generalization of learned values. AB - Sleep is thought to play an important role in memory consolidation. Here we tested whether sleep alters the subjective value associated with objects located in spatial clusters that were navigated to in a large-scale virtual town. We found that sleep enhances a generalization of the value of high-value objects to the value of locally clustered objects, resulting in an impaired memory for the value of high-valued objects. Our results are consistent with (a) spatial context helping to bind items together in long-term memory and serve as a basis for generalizing across memories and (b) sleep mediating memory effects on salient/reward-related items. PMID- 26373835 TI - Initiating pain and palliative care outpatient services for the suburban underserved in Montgomery County, Maryland: Lessons learned at the NIH Clinical Center and MobileMed. AB - OBJECTIVE: With the ongoing expansion of palliative care services throughout the United States, meeting the needs of socioeconomically marginalized populations, as in all domains of healthcare, continues to be a challenge. Our specific aim here was to help meet some of these needs through expanding delivery of pain and palliative care services by establishing a new clinic for underserved patients and collecting descriptive data about its operation. METHOD: In November of 2014, the National Institutes of Health Clinical Center's Pain and Palliative Care Service (PPCS) launched a bimonthly offsite pain and palliative care outpatient clinic in collaboration with Mobile Medical Care Inc. (MobileMed), a private not for-profit primary care provider in Montgomery County, Maryland, serving underserved area residents since 1968. Staffed by NIH hospice and palliative medicine clinical fellows and faculty, the clinic provides specialty pain and palliative care consultation services to patients referred by their primary care healthcare providers. A patient log was maintained, charts reviewed, and referring providers surveyed on their satisfaction with the service. RESULTS: The clinic had 27 patient encounters with 10 patients (6 males, 4 females, aged 23 67) during its first 7 months of operation. The reason for referral for all but one patient was chronic pain of multiple etiologies. Patients had numerous psychosocial stressors and comorbidities. All primary care providers who returned surveys (n = 4) rated their level of satisfaction with the consultation service as "very satisfied" or "extremely satisfied." SIGNIFICANCE OF RESULTS: This brief descriptive report outlines the steps taken and logistical issues addressed to launch and continue the clinic, the characteristics of patients treated, and the results of quality-improvement projects. Lessons learned are highlighted and future directions suggested for the clinic and others that may come along like it. PMID- 26373836 TI - A prospective analysis of blood donation history and risk of non-Hodgkin lymphoma. AB - Blood donation may influence subsequent NHL development via temporary immune system alterations. To test the hypothesis that frequent blood donation is associated with an increased risk of NHL and its most common histologic subtypes, this study followed 36 576 men in the Health Professionals Follow-up Study (HPFS), who provided information on frequency of blood donation in the past 30 years in 1992. This study confirmed 544 incident cases of NHL through 2010. Cox proportional hazards regression was used to calculate hazards ratios (HR) and 95% CI for the risk of all NHL and major NHL histologic subtypes associated with number of blood donations. In this prospective study, there was no significant evidence of an association between blood donation frequency and incidence of NHL (age-adjusted HR = 1.26, 95% CI = 0.94-1.68, comparing > 20 donations vs 0 donations over 30 years, p for trend = 0.18) or of any major NHL subtypes. PMID- 26373838 TI - Strain-induced stereoselective formation of blue-emitting cyclostilbenes. AB - We describe the synthesis of two conjugated macrocycles that are formed from the end-to-end linking of stilbenes. We have named these macrocycles cyclostilbenes. The two cyclostilbene isomers created in this study differ in the configuration of the double bond in their subunits. These macrocycles are formed selectively through a stepwise reductive elimination from a tetraplatinum precursor and subsequent photoisomerization. Single-crystal X-ray diffraction reveals the formation of channel architectures in the solid state that can be filled with guest molecules. The cyclostilbene macrocycles emit blue light with fluorescence quantum yields that are high (>50%) and have photoluminescence lifetimes of ~0.8 1.5 ns. The breadth and large Stokes shift in fluorescence emission, along with broad excited-state absorption, result from strong electronic-vibronic coupling in the strained structures of the cyclostilbenes. PMID- 26373837 TI - 1H-pyrrole-2,5-dione-based small molecule-induced generation of mesenchymal stem cell-derived functional endothelial cells that facilitate rapid endothelialization after vascular injury. AB - INTRODUCTION: Despite the success of interventional processes such as drug eluting stents, complete prevention of restenosis is still hindered by impaired or delayed endothelialization or both. Here, we report that 1H-pyrrole-2,5-dione based small molecule-generated mesenchymal stem cell-derived functional endothelial cells (MDFECs) facilitated rapid transmural coverage of injured blood vessels. METHODS: Small molecules that induced CD31 expression were screened by principal component analysis (PCA). Rat mesenchymal stem cells (MSCs) were treated with selected small molecules for up to 16 days, and the expression levels of CD90 and CD31 were examined by immunocytochemistry. In vitro functional assays of MDFECs, including tube formation assays and nitric oxide production assays, were performed. After MDFECs (intravenous, 3*10(6) cells per animal) were injected into balloon-injured rats, neointima formation was monitored for up to 21 days. The endothelial coverage of denuded blood vessels was evaluated by Evans Blue staining. The functionality of repaired blood vessels was evaluated by measuring vasorelaxation and hemodynamic changes. Additionally, derivatives of the selected small molecules were examined for their ability to induce endothelial markers. RESULTS: PCA indicated that 3-(2,4-dichlorophenyl)-4-(1 methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione effectively induced MDFECs. MDFECs inhibited the neointima formation of denuded blood vessels by facilitating more rapid endothelialization. Further examination indicated that derivatives with a 1H-pyrrole-2,5-dione moiety are important for initiating the endothelial cell differentiation of MSCs. CONCLUSIONS: Small molecules with 1H-pyrrole-2,5-dione as a core structure have great potential to improve the efficacy of MSC-based cell therapy for vascular diseases, such as atherosclerosis and restenosis. PMID- 26373840 TI - Erratum to: Are interventions to promote healthy eating equally effective for all? Systematic review of socioeconomic inequalities in impact. PMID- 26373839 TI - Recombinant human SIRT1 protects against nutrient deprivation-induced mitochondrial apoptosis through autophagy induction in human intervertebral disc nucleus pulposus cells. AB - INTRODUCTION: Nutrient deprivation is a likely contributor to intervertebral disc (IVD) degeneration. Silent mating type information regulator 2 homolog 1 (SIRT1) protects cells against limited nutrition by modulation of apoptosis and autophagy. However, little evidence exists regarding the extent to which SIRT1 affects IVD cells. Therefore, we conducted an in vitro study using human IVD nucleus pulposus (NP) cells. METHODS: Thirty-two IVD specimens were obtained from patients who underwent surgical intervention and were categorized based on Pfirrmann IVD degeneration grades. Cells were isolated from the NP and cultured in the presence of recombinant human SIRT1 (rhSIRT1) under different serum conditions, including 10 % (v/v) fetal bovine serum (FBS) as normal nutrition (N) and 1 % (v/v) FBS as low nutrition (LN). 3-Methyladenine (3-MA) was used to inhibit autophagy. Autophagic activity was assessed by measuring the absorbance of monodansylcadaverine and immunostaining and Western blotting for light chain 3 and p62/SQSTM1. Apoptosis and pathway analyses were performed by flow cytometry and Western blotting. RESULTS: Cells cultured under LN conditions decreased in number and exhibited enhanced autophagy compared with the N condition. Medium supplementation with rhSIRT1 inhibited this decrease in cell number and induced an additional increase in autophagic activity (P < 0.05), whereas the combined use of rhSIRT1 and 3-MA resulted in drastic decreases in cell number and autophagy (P < 0.05). The incidence of apoptotic cell death increased under the LN condition, which was decreased by rhSIRT1 (P < 0.05) but increased further by a combination of rhSIRT1 and 3-MA (P < 0.05). Under LN conditions, NP cells showed a decrease in antiapoptotic Bcl-2 and an increase in proapoptotic Bax, cleaved caspase 3, and cleaved caspase 9, indicating apoptosis induction via the mitochondrial pathway. These changes were suppressed by rhSIRT1 but elevated further by rhSIRT1 with 3-MA, suggesting an effect of rhSIRT1-induced autophagy on apoptosis inhibition. Furthermore, the observed autophagy and apoptosis were more remarkable in cells from IVDs of Pfirrmann grade IV than in those from IVDs of Pfirrmann grade II. CONCLUSIONS: SIRT1 protects against nutrient deprivation induced mitochondrial apoptosis through autophagy induction in human IVD NP cells, suggesting that rhSIRT1 may be a potent treatment agent for human degenerative IVD disease. PMID- 26373841 TI - Healthcare professionals' views on patient-centered care in hospitals. AB - BACKGROUND: Patient-centered care (PCC) is a main determinant of care quality. Research has shown that PCC is a multi-dimensional concept, and organizations that provide PCC well report better patient and organizational outcomes. However, little is known about the relative importance of PCC dimensions. The aim of this study was therefore to investigate the relative importance of the eight dimensions of PCC according to hospital-based healthcare professionals, and examine whether their viewpoints are determined by context. METHODS: Thirty-four healthcare professionals (16 from the geriatrics department, 15 from a surgical intensive care unit, 3 quality employees) working at a large teaching hospital in New York City were interviewed using Q methodology. Participants were asked to rank 35 statements representing eight dimensions of PCC extracted from the literature: patient preferences, physical comfort, coordination of care, emotional support, access to care, continuity and transition, information and education and family and friends. By-person factor analysis was used to reveal patterns of communality in statement rankings, which were interpreted and described as distinct viewpoints. RESULTS: Three main viewpoints on elements important for PCC were identified: "treating patients with dignity and respect," "an interdisciplinary approach" and "equal access and good outcomes." In these viewpoints, not all dimensions were equally important for PCC. Furthermore, the relative importance of the dimensions differed between departments. Context thus appeared to affect the relative importance of PCC dimensions. CONCLUSION: Healthcare organizations wishing to improve PCC should consider the relative importance of PCC dimensions in their specific context of care provision, which may help to improve levels of patient-centeredness in a more efficient and focused manner. However, as the study sample is not representative and consisted only of professionals (not patients), the results cannot be generalized outside the sample. More research is needed to confirm our study findings. PMID- 26373842 TI - Excess TNF-alpha in the blood activates monocytes with the potential to directly form cholesteryl ester-laden cells. AB - The tumor necrosis factor-alpha (TNF-alpha) and monocytic cells play a critical role in the development of atherosclerosis, which is the major cause of coronary heart disease (CHD). In this work, we investigated the effect of excess TNF-alpha on monocytes in the blood and found that blood monocytes from the CHD patients had the potential to directly form cholesteryl ester (CE)-laden cells under the in vitro incubation with oxLDL. The plasma levels of proinflammatory cytokines, such as TNF-alpha, interleukin 6 (IL-6), and C reactive protein (CRP), in the CHD patients were significantly higher than those in the control healthy volunteers. However, only the plasma level of TNF-alpha, but not of IL-6 or CRP, is positively correlated with the potential of blood monocytes to directly form CE laden cells. By using human blood monocytes and monocytic THP-1 cells, the activating effect of TNF-alpha on the formation of the CE-laden cells was demonstrated, which could be specifically blocked by the anti-TNF-alpha antibody. Furthermore, it was also revealed that TNF-alpha could boost adhesion and oxLDL uptake of the monocytes by enhancing the expression of the functional adhesion molecules and scavenger receptors, respectively. Finally, the results of in vivo and in vitro experiments with a mouse model confirmed that excess TNF-alpha in the blood activates monocytes with the potential to directly form CE-laden cells. These data demonstrate that excess TNF-alpha in the blood is the primary trigger for the development of atherosclerosis and CHD. PMID- 26373843 TI - Dendritic cell-based vaccination with lentiviral vectors encoding ubiquitinated hepatitis B core antigen enhances hepatitis B virus-specific immune responses in vivo. AB - The activity of hepatitis B virus (HBV)-specific cytotoxic T lymphocytes (CTLs) plays a predominant role in the clearance of HBV. Dendritic cells (DCs) are key antigen-presenting cells and play an important role in the initiation of immune responses. We previously verified that lentiviral vector encoding ubiquitinated hepatitis B core antigen (LV-Ub-HBcAg) effectively transduced DCs to induce maturation, and the mature DCs efficiently induced T cell polarization to Th1 and generated HBcAg-specific CTLs ex vivo. In this study, HBV-specific immune responses of LV-Ub-HBcAg in BALB/c mice (H-2Kd) were evaluated. It was shown that direct injection of LV-Ub-HBcAg increased the production of cytokines IL-2 and IFN-gamma, elicited strong antibody responses, and remarkably generated a high percentage of IFN-gamma+CD8+ T cells with HBV-specific CTL responses in BALB/c mice. In addition, direct injection of LV-Ub-HBcAg induced potent anti-HBV immune responses, similar to those elicited by in vitro-transduced DCs. In conclusion, the DC-based therapeutic vaccine LV-Ub-HBcAg elicited specific antibody immune responses and induced robust specific CTL activity in vivo. PMID- 26373845 TI - Somatic musculature in trematode hermaphroditic generation. AB - BACKGROUND: The somatic musculature in trematode hermaphroditic generation (cercariae, metacercariae and adult) is presumed to comprise uniform layers of circular, longitudinal and diagonal muscle fibers of the body wall, and internal dorsoventral muscle fibers. Meanwhile, specific data are few, and there has been no analysis taking the trunk axial differentiation and regionalization into account. Yet presence of the ventral sucker (= acetabulum) morphologically divides the digenean trunk into two regions: preacetabular and postacetabular. The functional differentiation of these two regions is already evident in the nervous system organization, and the goal of our research was to investigate the somatic musculature from the same point of view. RESULTS: Somatic musculature of ten trematode species was studied with use of fluorescent-labelled phalloidin and confocal microscopy. The body wall of examined species included three main muscle layers (of circular, longitudinal and diagonal fibers), and most of the species had them distinctly better developed in the preacetabuler region. In majority of the species several (up to seven) additional groups of muscle fibers were found within the body wall. Among them the anterioradial, posterioradial, anteriolateral muscle fibers, and U-shaped muscle sets were most abundant. These groups were located on the ventral surface, and associated with the ventral sucker. The additional internal musculature was quite diverse as well, and included up to twelve separate groups of muscle fibers or bundles in one species. The most dense additional bundles were found in the preacetabular region and were connected with the suckers. CONCLUSIONS: Previously unknown additional somatic musculature probably provides the diverse movements of the preacetabular region, ventral sucker, and oral sucker (or anterior organ). Several additional muscle groups of the body wall (anterioradial, posterioradial, anteriolateral fibers and U-shaped sets) are proposed to be included into the musculature ground pattern of trematode hermaphroditic generation. This pattern is thought to be determined by the primary trunk morphofunctional differentiation into the preacetabular and the postacetabular regions. PMID- 26373844 TI - Identifying therapeutic targets in gastric cancer: the current status and future direction. AB - Gastric cancer is the third leading cause of cancer-related death worldwide. Our basic understanding of gastric cancer biology falls behind that of many other cancer types. Current standard treatment options for gastric cancer have not changed for the last 20 years. Thus, there is an urgent need to establish novel strategies to treat this deadly cancer. Successful clinical trials with Gleevec in CML and gastrointestinal stromal tumors have set up an example for targeted therapy of cancer. In this review, we will summarize major progress in classification, therapeutic options of gastric cancer. We will also discuss molecular mechanisms for drug resistance in gastric cancer. In addition, we will attempt to propose potential future directions in gastric cancer biology and drug targets. PMID- 26373847 TI - Toward a Developmentally Centered Approach to Adolescent Alcohol and Substance Use Treatment. AB - Adolescent alcohol and drug use disorders pose significant risks to adolescents' future functioning. Unfortunately, relapse rates following treatment for these disorders are high. The newest generation of interventions, designed in part to address this problem, place greater focus on the developmental needs of adolescents. In this review, we highlight the importance and promise of this progress in the field. We also argue for a further, more complete, integration of development and treatment: Instead of a focus on developmental issues as part of the process of substance use treatment, we argue for an approach in which healthy development is an outcome of equal importance to changes in substance use and risk behaviors. From this perspective, treatment should address the skills necessary for social, emotional, achievement, and identity development, with substance abuse understood as one example of dysfunctional development. We argue that this approach holds the greatest promise for providing adolescents in treatment with the skills they need to maintain successful post-treatment trajectories. In this paper, we offer theory underlying this perspective, a definition of the outcomes of healthy development that can guide researchers and clinicians, as well as proposals for both researchers and clinicians to continue to push the developmental sensitivity of adolescent substance use treatment forward. PMID- 26373846 TI - miR-363 induces transdifferentiation of human kidney tubular cells to mesenchymal phenotype. AB - BACKGROUND: microRNAs (miRNAs) are non-coding small RNAs that regulate embryonic development, cell differentiation and pathological processes via interaction with mRNA. Epithelial-mesenchymal transition (EMT) is pathological process that involves in a variety of diseases such as cancer or fibrosis. METHODS: In this study, we identified miR-363 as a potent inducer of EMT by microarray analysis in human kidney tubular cells, and analyzed the function and mechanisms of miR-363. RESULTS: Overexpression of miR-363 induced mesenchymal phenotypes with loss of epithelial phenotypes in human kidney tubular cells. In addition, in vitro scratch assay demonstrated that miR-363 promotes cell migration of primary culture of human kidney tubular cells. We identified TWIST/canonical WNT pathway as the downstream effecter of miR-363, and inhibition of canonical WNT by small molecule, IWR-1, attenuated EMT induced by miR-363. CONCLUSION: miR-363 induces transdifferentiation of human kidney tubular cells via upregulation of TWIST/canonical WNT pathway. PMID- 26373848 TI - A Systematic Review of Digital and Computer-Based Alcohol Intervention Programs in Primary Care. AB - BACKGROUND: Alcohol misuse is a significant public health issue resulting in substantial morbidity, premature mortality and costs to the healthcare system. Although face-to-face interventions offered by health practitioners have been shown to be effective, they are not routinely offered due to lack of time, training and resources, and potential damage to rapport. Computerbased interventions may help overcome these implementation barriers. APPROACH: Suitable research databases were searched and studies were selected if they described digital or computer-based alcohol interventions used by primary care patients. Studies which did not report patient alcohol outcomes were excluded. KEY FINDINGS: Fifteen trials were identified, eleven of which trialled brief interventions only while the remaining four trialled both brief and extended interventions. Nine trials were associated with a reduction in alcohol use at followup. CONCLUSION: This is the first systematic review of digital or computer based alcohol intervention programs used by primary care patients. Although the number of trials in this area of research is relatively small, their findings indicate effectiveness in reducing alcohol consumption as well as drinking related consequences. Extended interventions which offer additional opportunities to monitor drinking over time appear no more effective than single occasion brief interventions. These findings suggest that digital and computer-based interventions in primary care may have the potential to increase alcohol intervention activities in the general population at a relatively low cost and low burden on practitioners. PMID- 26373849 TI - Can Decision Making Research Provide a Better Understanding of Chemical and Behavioral Addictions? AB - We reviewed the cognitive and neurobiological commonalities between chemical and behavioral addictions. Poor impulse control, limited executive function and abnormalities in reward processing are seen in both group of entities. Brain imaging shows consistent abnormalities in frontoparietal regions and the limbic system. In drug addiction, exaggerated risk taking behavior and temporal discounting may reflect an imbalance between a hyperactive mesolimbic and hypoactive executive systems. Several cognitive distortions are found in pathological gambling that seems to harness the brain reward system that has evolved to face situations related to skill, not random chance. Abnormalities in risk assessment and impulsivity are found in variety of eating disorders, in particularly related to eating behavior. Corresponding findings in eating disorder patients include abnormalities in the limbic system, i.e. orbitofrontal cortex (OFC), striatum and insula. Similarly, internet addiction disorder is associated with risky decision making and increased choice impulsivity with corresponding discrepant activation in the dorsolateral prefrontal cortex, OFC, anterior cingulate cortex, caudate and insula. Sexual addictions are in turn associated with exaggerated impulsive choice and suggestive evidence of abnormalities in reward processing. In sum, exploration of executive function and decision making abnormalities in chemical and behavioral addictions may increase understanding in their psychopathology and yield valuable targets for therapeutic interventions. PMID- 26373850 TI - The Role of Different Aspects of Impulsivity as Independent Risk Factors for Substance Use Disorders in Patients with ADHD: A Review. AB - High impulsivity in children with attention deficit/hyperactivity disorder (ADHD) plays a key role in their vulnerability to substance abuse disorders (SUDs). Although impulsivity is increasingly recognized as a multidimensional construct, efforts to describe the contribution of different impulsivity aspects to the development of SUD have been hindered by conceptual and experimental inconsistencies. This review seeks to map potential trajectories from childhood ADHD to SUD by examining the hypothesized mediating role of three different impulsivity-related constructs: disinhibition, impulsive choice, and sensation seeking. Integration of data from developmental, cognitive, and neurophysiological research suggests that childhood ADHD and SUD are both associated with behavioural and neurophysiological deficits in all three impulsivity-related constructs. Examination of brain mechanisms related to the three impulsivity-related constructs indicates that ADHD share neurophysiological deficits with SUD, such as abnormal brain activity in areas involved in inhibition and complex cognitive-emotional processes. We conclude that different impulsivity constructs operate independently and interact with each other to affect adult risk taking behaviour and SUD in patients with childhood ADHD. This review highlights the current theoretical and methodological challenges in the study of impulsivity and discusses clinical implications and directions for future research. PMID- 26373851 TI - Does a titanium-coated polyethylene press-fit cup give reliable midterm results? AB - BACKGROUND: Uncemented acetabular components have demonstrated low revision rates and high patient satisfaction but with concerns regarding increased costs compared with monoblock cups. Some newer lower-cost uncemented monoblock options have become available in the last decade, but limited data are available on their performance. QUESTIONS/PURPOSES: (1) Does an uncemented, titanium-backed all polyethylene acetabular cup provide reliable fixation? (2) What is the frequency and what are the causes for revision with this cup? METHODS: Between 2004 and 2008, we elected to use an uncemented, titanium-backed all-polyethylene acetabular cup in older patients with limited physical demands. We performed 615 hip replacements in 550 patients with greater than 5 years of clinical and radiographic followup. When patients who were dead (80 hips in 75 patients), lost to followup (98 hips in 93 patients), or revised (three hips in three patients) were excluded, there were 434 hips in 379 patients for comparison of the postoperative and 5-year radiographs. Two observers not involved in the index surgical procedures (NH, HS) assessed radiographs for signs of migration or loosening. Some degree of early movement sometimes is seen before cup stabilization; however, to be conservative, we defined cups with greater than 3 degrees of change of position (even if they subsequently stabilized) as potentially at risk and report them separately. Revision surgery, time from the index procedure, and the reason for revision were recorded from the New Zealand Joint Registry. RESULTS: By 5 years there was a median change in inclination of 2 degrees (range, 0 degrees -13 degrees ; 95% confidence interval [CI], 2.0-2.4; p < 0.001) and 2 degrees of anteversion (range, 0 degrees -11 degrees ; 95% CI, 2.0-2.4; p < 0.001). Although at last followup all cups appeared to have stabilized with no radiolucent lines or medial migration, 22% of the cups (94 of 434) had moved more than 3 degrees and so were deemed to be potentially at risk. There were 11 revision procedures (of 429 hips; 2.5%) of which six were for recurrent dislocation, four for femoral fracture, and one for femoral loosening to give an overall all-cause revision rate for all components of 0.25 per 100 component years (95% CI, 0.13-0.43). No revisions were performed for acetabular loosening. CONCLUSIONS: The short- to medium-term results of this all polyethylene monoblock cup demonstrated a low frequency of revision. However, 94 cups were identified as potentially at risk based on movement of > 3 degrees before apparent stabilization. Although those patients seem to be doing well enough now, the current duration of followup may not be sufficient to know that these cups will be durable, because other ongrowth designs have demonstrated a high frequency of late failure after apparent early success. LEVEL OF EVIDENCE: Level IV, therapeutic study. PMID- 26373852 TI - Evaluation of point-of-care PRO assessment in clinic settings: integration, parallel-forms reliability, and patient acceptability of electronic QOL measures during clinic visits. AB - PURPOSE: Assessment of patient-reported outcomes (PROs), such as health-related quality of life, has become an important component of healthcare that measures the impact of disease and medical treatment on patient health. Collecting PROs during point-of-care assessments and integrating them into the clinical setting, however, remains challenging. The objective of this pilot study was to evaluate the reliability, usability, and acceptability of point-of-care electronic PRO assessments implemented in a prostate cancer clinic. METHODS: Fifty subjects completed paper-pencil and computerized formats of the Expanded Prostate Cancer Index Composite (EPIC), a validated, condition-specific QOL instrument, at separate times before treatment. Parallel-forms reliability was evaluated by comparing mean scores, variations in response distribution, and correlations between administration formats. Correlation coefficients of at least 0.70 were used for reliability testing. Differences between administration forms, indicating potential bias, were compared using the signed-rank test. A 6-item acceptability scale was also used to evaluate patient acceptability and satisfaction with the electronic format. RESULTS: Mean scores and standard deviations were similar between the paper-pencil and electronic forms across all EPIC instrument domains, and no assessment bias was found. Each EPIC domain demonstrated a high reliability between administration formats (correlation coefficients: 0.70-0.98). The majority (>90 %) of respondents found that the computerized QOL format was user friendly and simple to use. CONCLUSIONS: Point of-care computerized QOL assessments were reliable and acceptable to patients in this study, supporting the feasibility of PRO integration at the point-of-care in clinical settings. PMID- 26373854 TI - The DSM-5 effect: psychological characteristics of new patients affected by Binge Eating Disorder following the criteria of the DSM-5 in a sample of severe obese patients. AB - PURPOSE: The current study evaluated whether or not there were significant differences in psychopathological traits between three groups of individuals. The first was a group of patients seeking bariatric surgery diagnosed as being affected by Binge Eating Disorder (BED), according to the new criteria of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders. This group (NEW BED group) did not meet BED diagnosis following the previous criteria listed in the DSM-IV-TR. The second group of individuals was composed of severely obese patients seeking bariatric surgery not affected by an eating disorder, according to the diagnostic criteria of the DSM-5 (OB group). The third group was composed of individuals within a healthy weight range (Control group). METHODS: 94 severely obese patients (33 in the NEW BED group and 61 in the OB group) were compared to the Control group including 41 participants on depression, anxiety and eating habits. RESULTS: The NEW BED scored significantly higher than the OB group on the Beck Depression Inventory, both the subscales of the State Trait Anxiety Inventory, on disinhibition and hunger subscales of the Three-Factor Eating Questionnaire and on many subscales of the Eating Disorders Inventory. CONCLUSIONS: The new, less restrictive diagnostic criteria for BED of the DSM-5 are useful in identifying obese patients affected by severe psychopathology and dysfunctional eating habits. PMID- 26373853 TI - Carotid body oxygen sensing and adaptation to hypoxia. AB - The carotid body (CB) is the principal arterial chemoreceptor that mediates the hyperventilatory response to hypoxia. Our understanding of CB function and its role in disease mechanisms has progressed considerably in the last decades, particularly in recent years. The sensory elements of the CB are the neuron-like glomus cells, which contain numerous transmitters and form synapses with afferent sensory fibers. The activation of glomus cells under hypoxia mainly depends on the modulation of O2-sensitive K(+) channels which leads to cell depolarization and the opening of Ca(2+) channels. This model of sensory transduction operates in all mammalian species studied thus far, including man. However, the molecular mechanisms underlying the modulation of ion channel function by changes in the O2 level are as yet unknown. The CB plays a fundamental role in acclimatization to sustained hypoxia. Mice with CB atrophy or patients who have undergone CB resection due to surgical treatments show a marked intolerance to even mild hypoxia. CB growth under hypoxia is supported by the existence of a resident population of neural crest-derived stem cells of glia-like phenotype. These stem cells are not highly affected by exposure to low O2 tension; however, there are abundant synapse-like contacts between the glomus cells and stem cells (chemoproliferative synapses), which may be needed to trigger progenitor cell proliferation and differentiation under hypoxia. CB hypo- or hyper-activation may also contribute to the pathogenesis of several prevalent human diseases. PMID- 26373855 TI - Pollinators, pests, and predators: Recognizing ecological trade-offs in agroecosystems. AB - Ecological interactions between crops and wild animals frequently result in increases or declines in crop yield. Yet, positive and negative interactions have mostly been treated independently, owing partly to disciplinary silos in ecological and agricultural sciences. We advocate a new integrated research paradigm that explicitly recognizes cost-benefit trade-offs among animal activities and acknowledges that these activities occur within social-ecological contexts. Support for this paradigm is presented in an evidence-based conceptual model structured around five evidence statements highlighting emerging trends applicable to sustainable agriculture. The full range of benefits and costs associated with animal activities in agroecosystems cannot be quantified by focusing on single species groups, crops, or systems. Management of productive agroecosystems should sustain cycles of ecological interactions between crops and wild animals, not isolate these cycles from the system. Advancing this paradigm will therefore require integrated studies that determine net returns of animal activity in agroecosystems. PMID- 26373856 TI - Magnetic susceptibility and isothermal remanent magnetization in human tissues: a study case. AB - This study evaluated the magnetic properties, magnetic susceptibility and isothermal remanent magnetization (IRM) of tissue samples from the brain, liver, spleen, pancreas, heart and lungs, resected from human corpses, with the aim of identifying the magnetic mineral structures and understanding their possible connection to diseases, professional activity, age and gender of the individual, smoking habits and the environment. The heart was the organ with the highest values of magnetic susceptibility and the pancreas showed the lowest values. No relationship was found between magnetic susceptibility, IRM values and ages of the individuals. However the samples obtained in females showed lower values of magnetic susceptibility than those resected from males. The samples collected from the lungs of smokers have higher values of magnetic susceptibility and IRM indicating the presence of magnetic particles with an anthropic origin. Moreover, the complexity of the magnetic behaviour of these tissues may suggest a contribution of both biogenic and anthropogenic magnetic particles also due to some professional activities. In the brain a heterogeneous distribution of the magnetic susceptibility values was found, which might be related mainly to the diamagnetic behaviour of myelin-rich structures. This study suggests that although the diamagnetic and paramagnetic behaviour is common to all structures, magnetite-type structures are always present in the tissues and hematite-type structures may also contribute to the magnetic signal of the sample. IRM values are only dependent on the presence of magnetite or hematite-type magnetic structures and so this technique seems more suitable to achieve the characterization of biomagnetic structures than magnetic susceptibility. PMID- 26373857 TI - Evidence for altered cholesterol metabolism in Huntington's disease post mortem brain tissue. AB - AIMS: Cholesterol plays an essential role in membrane structure and function, being especially important in the brain. Alteration of brain cholesterol synthesis and metabolism has been demonstrated in several Huntington's disease (HD) mouse and cell models; however, less is known about these alterations in human tissue. This study aimed to identify alterations to cholesterol synthetic and metabolic pathways in human HD brain tissue. METHODS: A broad range of cholesterol synthetic precursors, metabolites and oxidation products were measured by gas chromatography-tandem mass spectrometry in five regions of human post mortem HD brain and compared with age- and sex-matched control tissues. The level of enzymes that regulate cholesterol homeostasis, cholesterol 24 hydroxylase and delta(24)-sterol reductase were investigated by Western blotting and qPCR in putamen. RESULTS: The most significant changes were localized to the putamen, where a 60% decrease in 24(S)-hydroxycholesterol, 30% increase in cholesterol and 100-200% increase in synthetic precursors (lathosterol, zymosterol and desmosterol) was detected. The enzymes cholesterol 24-hydroxylase and delta(24)-sterol reductase were also significantly decreased in HD putamen as compared with control tissues. Free radical-generated cholesterol oxidation products 7-keto cholesterol and 7beta-hydroxycholesterol were also increased by 50-70% in HD putamen. CONCLUSION: Human HD brain has significantly decreased cholesterol metabolism and disrupted cholesterol homeostasis. Our data also indicate that lipid oxidative stress accompanies HD pathology. PMID- 26373859 TI - The multifunctional protein CI of potyviruses plays interlinked and distinct roles in viral genome replication and intercellular movement. AB - BACKGROUND: The multifunctional cylindrical inclusion (CI) protein of potyviruses contains ATP binding and RNA helicase activities. As part of the viral replication complex, it assists viral genome replication, possibly by binding to RNA and unwinding the RNA duplex. It also functions in viral cell-to-cell movement, likely via the formation of conical structures at plasmodesmata (PD) and the interaction with coat protein (CP). METHODS: To further understand the role of CI in the viral infection process, we employed the alanine-scanning mutagenesis approach to mutate CI in the infectious full-length cDNA clone of Turnip mosaic virus (TuMV) tagged by green fluorescent protein. A total of 40 double-substitutions were made at the clustered charged residues. The effect of these mutations on viral genome amplification was determined using a protoplast inoculation assay. All the mutants were also introduced into Nicotiana benthamiana plants to assess their cell-to-cell and long-distance movement. Three cell-to-cell movement-abolished mutants were randomly selected to determine if their mutated CI protein targets PD and interacts with CP by confocal microscopy. RESULTS: Twenty CI mutants were replication-defective (5 abolished and 15 reduced), one produced an elevated level of viral genome in comparison with the parental virus, and the remaining 19 retained the same replication level as the parental virus. The replication-defective mutations were predominately located in the helicase domains and C-terminal region. All 15 replication-reduced mutants showed delayed or abolished cell-to-cell movement. Nine of 20 replication competent mutants contained infection within single cells. Five of them distributed mutations within the N-terminal 100 amino acids. Most of replication defective or cell-to-cell movement-abolished mutants failed to infect plants systemically. Analysis of three randomly selected replication-competent yet cell to-cell movement-abolished mutants revealed that the mutated CI failed to form regular punctate structures at PD and/or to interact with CP. CONCLUSIONS: The helicase domain and C-terminal region of TuMV CI are essential for viral genome replication, and the N-terminal sequence modulates viral cell-to-cell movement. TuMV CI plays both interlinked and distinct roles in replication and intercellular movement. The ability of CI to target PD and interact with CP is associated with its functional role in viral cell-to-cell movement. PMID- 26373861 TI - The International Mouse Strain Resource (IMSR): cataloging worldwide mouse and ES cell line resources. AB - The availability of and access to quality genetically defined, health-status known mouse resources is critical for biomedical research. By ensuring that mice used in research experiments are biologically, genetically, and health-status equivalent, we enable knowledge transfer, hypothesis building based on multiple data streams, and experimental reproducibility based on common mouse resources (reagents). Major repositories for mouse resources have developed over time and each has significant unique resources to offer. Here we (a) describe The International Mouse Strain Resource that offers users a combined catalog of worldwide mouse resources (live, cryopreserved, embryonic stem cells), with direct access to repository sites holding resources of interest and (b) discuss the commitment to nomenclature standards among resources that remain a challenge in unifying mouse resource catalogs. PMID- 26373862 TI - Theoretical Applications of Positive Psychology to Vocational Rehabilitation After Traumatic Brain Injury. AB - PURPOSE: Traumatic brain injury (TBI) produces broad-reaching and often persistent challenges that impact an individual's ability to engage in vocational productivity. Return to work (RTW) rates after TBI are markedly poor and the efficacy of current TBI vocational rehabilitation (VR) practices is unclear. Positive psychology, the practice of fostering positive emotions and traits, offers novel approaches that might enhance the effectiveness of existing TBI VR practices. This article assesses the potential relevance of positive psychology principles and practices to VR for clients recovering from TBI. METHODS: A literature search was conducted using the database resources of a large university hospital, including PubMed, ProQuest, PsycINFO, and Web of Science. Content from this search was reviewed and synthesized, including literature on VR for TBI, vocational applications of positive psychology, and general rehabilitation applications of positive psychology. RESULTS: Ten guiding principles for positively-informed TBI VR are proposed. Specific positive psychology measures and interventions for improving emotional, social, and cognitive functioning are identified and discussed as they might be applied to TBI VR. CONCLUSIONS: Theoretically, positive psychology principles and practices appear to be well suited to improving VR outcomes for individuals with TBI. In addition to examining the feasibility of incorporating positive psychology techniques, future research should examine the impact of positive psychology interventions on RTW rates, job satisfaction, job stability, and other vocational outcomes. With additional investigation, positive psychology measures and interventions may prove to be a beneficial compliment to existing VR practices. PMID- 26373860 TI - Kupffer phase image of Sonazoid-enhanced US is useful in predicting a hypervascularization of non-hypervascular hypointense hepatic lesions detected on Gd-EOB-DTPA-enhanced MRI: a multicenter retrospective study. AB - BACKGROUND: It remains unknown whether Kupffer-phase images in Sonazoid-enhanced ultrasonography (US) can be used to predict hypervascularization of borderline lesions. Therefore, we aimed to clarify whether Kupffer-phase images in Sonazoid enhanced ultrasonography can predict subsequent hypervascularization in hypovascular borderline lesions detected on hepatobiliary-phase gadolinium ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging. METHODS: From January 2008 to March 2012, 616 low-intensity hypovascular nodules were detected in hepatobiliary-phase images of Gd-EOB-DTPA enhanced MRI at nine institutions. Among these, 167 nodules, which were confirmed as hypovascular by Gd-EOB-DTPA-enhanced MRI and Sonazoid-enhanced US, were evaluated in this study. Potential hypervascularization factors were selected based on their clinical significance and the results of previous reports. The Kaplan-Meier model and log-rank test were used for univariate analysis and the Cox regression model was used for multivariate analysis. RESULTS: The cumulative incidence of hypervascularization of borderline lesions was 18, 37, and 43 % at 1, 2, and 3 years, respectively. Univariate analyses showed that tumor size (p = 0.0012) and hypoperfusion on Kupffer-phase images in Sonazoid-enhanced US (p = 0.004) were associated with hypervascularization of the tumor. Multivariate analysis showed that tumor size [HR: 1.086, 95 % confidence interval = 1.027 1.148, p = 0.004] and hypo perfusion on Kupffer-phase images [HR: 3.684, 95 % confidence interval = 1.798-7.546, p = 0.0004] were significantly different. CONCLUSIONS: Kupffer-phase images in Sonazoid-enhanced US and tumor diameter can predict hypervascularization of hypointense borderline lesions detected on hepatobiliary-phase Gd-EOB-DTPA-enhanced MRI. PMID- 26373863 TI - The identification and characteristics of salinity-related microRNAs in gills of Portunus trituberculatus. AB - MicroRNAs (miRNAs) are small noncoding RNAs that post-transcriptionally regulate gene expression in organisms. To understand the underlying mechanisms behind the molecular response of the crab to low salt-stress, high-throughput Illumina/Solexa deep sequencing technology was used to investigate the expression profiles of miRNAs under low salinity challenged. Two mixed RNA pool libraries of gill tissues from low salinity challenged (LC) and the control groups (NC) were sequenced on the Illumina platform. A total of 6,166,057 and 7,032,973 high quality reads were obtained from the NC and LC libraries, respectively. Sixty seven miRNAs consisting of 16 known and 51 novel ones were identified, among which, 12 miRNAs were differentially expressed in LC compared to NC. Thirty-four of the target genes predicted were differentially expressed in the opposite direction to the miRNAs, which were involved in crucial processes related to osmoregulation by gene ontology (GO) functional enrichment analysis, such as anion transport processes (GO:0006820) and chitin metabolic process (GO:0006030). These results provide a basis for further investigation of the miRNA-modulating networks in osmoregulation of Portunus trituberculatus. PMID- 26373865 TI - Idiopathic atrophoderma of Pasini-Pierini associated with morphea: the same disease spectrum? PMID- 26373866 TI - Association between isolated female acne and insulin resistance: a prospective study. AB - BACKGROUND: Acne is one of the manifestations of the polycystic ovary syndrome (PCOS). Nowadays hyperinsulinemia and insulin resistance are well-known characteristics of PCOS. The aim of this study was to investigate the relation between isolated female acne and insulin resistance and to determine the effect of hyperandrogenemia in this possible relationship. METHODS: Forty five women with acne and 24 healthy women aged 25-40 were included in the study. The global acne grading system (GAGS) was used to evaluate acne severity. Blood samples were drawn for measurements of hormone profile, basal insulin and fasting blood glucose (FBG). The oral glucose tolerance test (OGTT) was performed on another day. homeostasis model assessment (HOMA) score was used to assess insulin resistance (IR). All subjects underwent abdominopelvic sonography. RESULTS: Thirty-six women with acne and 24 healthy women were analyzed after exclusion. Fifteen (42%) patients had moderate acne, 11 (30%) had severe acne and 10 (28%) had very severe acne. Basal insulin, FBG, AUC glucose, AUC insulin and HOMA values were significantly higher in patients with acne when compared with the control group (P<0.05). After excluding patients with hyperandrogenemia, we compared the patients (N.=22) and control group with regard to IR; the serum basal insulin, AUC-insulin and AUC-glucose as well as HOMA score were still significantly higher in patients (P<0.05). CONCLUSIONS: We concluded that there is a relationship between female acne and IR. This association is independent of hyperandrogenemia. Anti-insulin drugs may an adjunctive treatment of female acne. PMID- 26373864 TI - Umbilical cord mesenchymal stem cell-conditioned media prevent muscle atrophy by suppressing muscle atrophy-related proteins and ROS generation. AB - The therapeutic potential of mesenchymal stem cell-conditioned medium (MSC-CM) has been reported with various types of disease models. Here, we examine the therapeutic effect of umbilical cord MSC-CM (UCMSC-CM) on muscle-related disease, using a dexamethasone (Dex)-induced muscle atrophy in vitro model. The expressions of muscle atrophy-related proteins (MuRF-1 and MAFbx) and muscle specific proteins (desmin and myogenin) were evaluated by Western blot analysis. The level of production of reactive oxygen species (ROS) was determined using a 2',7'-dichlorofluorescein diacetate (DCFDA) dye assay. The expression of antioxidant enzymes (copper/zinc-superoxide dismutase (Cu/Zn-SOD), manganese superoxide dismutase (MnSOD), glutathione peroxidase-1 (GPx-1), and catalase (CAT)) was verified by reverse transcription polymerase chain reaction (RT-PCR). When L6 cells were exposed to Dex, the expression of muscle atrophy-related proteins was increased by 50-70%, and the expression of muscle-specific proteins was in turn decreased by 23-40%. Conversely, when the L6 cells were co-treated with UCMSC-CM and Dex, the expression of muscle atrophy-related proteins was reduced in a UCMSC-CM dose-dependent manner and the expression of muscle-specific proteins was restored to near-normal levels. Moreover, ROS generation was effectively suppressed and the expression of antioxidant enzymes was recovered to a normal degree. These data imply that UCMSC-CM clearly has the potential to prevent muscle atrophy. Thus, our present study offers fundamental data on the potential treatment of muscle-related disease using UCMSC-CM. PMID- 26373867 TI - The skin barrier function: differences between intrinsic and extrinsic aging. AB - AIM: Transepidermal water loss (TEWL), stratum corneum hydration (SCH), and the skin surface pH are important parameters to characterize the skin barrier function. The aim of this exploratory study was to compare TEWL, SCH and skin surface-pH on sun-protected versus sun-exposed skin areas in relation to age. METHODS: Twenty four female subjects with healthy skin were recruited in three age groups. Lifetime sun exposure was assessed using a questionnaire. TEWL, SCH, and skin surface pH were measured on the right upper inner arm, right mid-volar forearm and right dorsal forearm under standardized conditions. RESULTS: Mean ages (SD) of the three age groups were 33.5 (2.1), 55.4 (2.7), and 76.6 (1.9) years. There were no TEWL differences between the age groups on either skin area. Significantly lower TEWL values were observed on the dorsal forearm compared to the other skin areas (P<0.05). Mean SCH was comparable between the age groups. Higher SCH values were measured on the volar forearm (P<0.05). Skin surface pH on the upper inner arm was significantly higher in the aged group (P=0.023). The dorsal forearm skin had a lower pH than the upper inner arm. CONCLUSION: There seem to be minor changes of TEWL and SCH, but a clear increase of skin surface pH during the course of life. Differences between intrinsically and extrinsically aged skin areas were observed, but results provide no clear evidence for an impairment of the skin barrier function due to photodamage. PMID- 26373868 TI - Electric field control of magnetic states in isolated and dipole-coupled FeGa nanomagnets delineated on a PMN-PT substrate. AB - We report observation of a 'non-volatile' converse magneto-electric effect in elliptical FeGa nanomagnets delineated on a piezoelectric PMN-PT substrate. The nanomagnets are first magnetized with a magnetic field directed along their nominal major axes. Subsequent application of a strong electric field across the piezoelectric substrate generates strain in the substrate, which is partially transferred to the nanomagnets and rotates the magnetizations of some of them away from their initial orientations. The rotated magnetizations remain in their new orientations after the field is removed, resulting in 'non-volatility'. In isolated nanomagnets, the magnetization rotates by <90 degrees upon application of the electric field, but in a dipole-coupled pair consisting of one 'hard' and one 'soft' nanomagnet, which are both initially magnetized in the same direction by the magnetic field, the soft nanomagnet's magnetization rotates by [Formula: see text] upon application of the electric field because of the dipole influence of the hard nanomagnet. This effect can be utilized for a nanomagnetic NOT logic gate. PMID- 26373870 TI - Dynamic exometabolome analysis reveals active metabolic pathways in non replicating mycobacteria. AB - An organism's metabolic activity leaves an extracellular footprint and dynamic changes in this exometabolome inform about nutrient uptake, waste disposal and signalling activities. Using non-targeted mass spectrometry, we report exometabolome dynamics of hypoxia-induced, non-replicating mycobacteria that are thought to play a role in latent tuberculosis. Despite evidence of active metabolism, little is known about the mechanisms enabling obligate aerobic mycobacteria to cope with hypoxia, resulting in long-term survival and increased chemotherapeutic tolerance. The dynamics of 379 extracellular compounds of Mycobacterium smegmatis were deconvoluted with a genome-scale metabolic reaction pair network to generate hypotheses about intracellular pathway usage. Time resolved (13) C-tracing and mutant experiments then demonstrated a crucial, energy-generating role of asparagine utilization and non-generic usage of the glyoxylate shunt for hypoxic fitness. Experiments with M. bovis and M. tuberculosis revealed the general relevance of asparagine fermentation and a variable contribution of the glyoxylate shunt to non-replicative, hypoxic survival between the three species. PMID- 26373869 TI - Predictors for persistent urodynamic stress incontinence following extensive pelvic reconstructive surgery with and without midurethral sling. AB - INTRODUCTION AND HYPOTHESIS: The objective of this study was to identify the predictors for persistent urodynamic stress incontinence (P-USI) in women following extensive pelvic reconstructive surgery (PRS) with and without midurethral sling (MUS). MMETHODS: A total of 1,017 women who underwent pelvic organ prolapse (POP) surgery from January 2005 to December 2013 in our institutions were analyzed. We included 349 USI women who had extensive PRS for POP stage III or more of whom 209 underwent concomitant MUS. RESULTS: Of the women who underwent extensive PRS without MUS, 64.3 % (90/140) developed P-USI compared to only 10.5 % (22/209) of those who had concomitant MUS. Those with concomitant MUS and PRS alone were at higher risk of developing P-USI if they had overt USI [odds ratio (OR) 2.2, 95 % confidence interval (CI) 1.3-4.0, p = 0.014 and OR 4.7, 95 % CI 2.0-11.3, p < 0.001, respectively], maximum urethral closure pressure (MUCP) of < 60 cm H2O (OR 5.0, 95 % CI 3.0-8.1, p < 0.001 and OR 5.3, 95 % CI 2.7-10.4, p < 0.001, respectively), and functional urethral length (FUL) of < 2 cm (OR 5.4, 95 % CI 2.7-8.8, p < 0.001 and OR 3.9, 95 % CI 2.4-6.9, p < 0.001, respectively). Parity >= 6 (OR 3.9, 95 % CI 1.7-5.2, p < 0.001) and Prolift T (OR 3.1, 95 % CI 1.9-4, p < 0.001) posed a higher risk of P-USI in those with concomitant surgery. Perigee and Avaulta A seemed to be protective against P-USI in those without MUS. CONCLUSIONS: Overt USI with advanced POP together with low MUCP and FUL values have a higher risk of developing P-USI. Therefore, counseling these women is worthwhile while considering the type of mesh used. PMID- 26373873 TI - Survival outcomes in liver transplant recipients with Model for End-stage Liver Disease scores of 40 or higher: a decade-long experience. AB - BACKGROUND: The Model for End-stage Liver Disease (MELD) has been used as a prognostic tool since 2002 to predict pre-transplant mortality. Increasing proportions of transplant candidates with higher MELD scores, combined with improvements in transplant outcomes, mandate the need to study surgical outcomes in patients with MELD scores of >=40. METHODS: A retrospective longitudinal analysis of United Network for Organ Sharing (UNOS) data on all liver transplantations performed between February 2002 and June 2011 (n = 33,398) stratified by MELD score (<30, 30-39, >=40) was conducted. The primary outcomes of interest were short- and longterm graft and patient survival. A Kaplan-Meier product limit method and Cox regression were used. A subanalysis using a futile population was performed to determine futility predictors. RESULTS: Of the 33,398 transplant recipients analysed, 74% scored <30, 18% scored 30-39, and 8% scored >=40 at transplantation. Recipients with MELD scores of >=40 were more likely to be younger (P < 0.001), non-White and to have shorter waitlist times (P < 0.001). Overall patient survival correlated inversely with increasing MELD score; this trend was consistent for both short-term (30 days and 90 days) and longterm (1, 3 and 5 years) graft and patient survival. In multivariate analysis, increasing age, African-American ethnicity, donor obesity and diabetes were negative predictors of survival. Futility predictors included patient age of >60 years, obesity, peri-transplantation intensive care unit hospitalization with ventilation, and multiple comorbidities. CONCLUSIONS: Liver transplantation in recipients with MELD scores of >=40 offers acceptable longterm survival outcomes. Futility predictors indicate the need for prospective follow-up studies to define the population to gain the highest benefit from this precious resource. PMID- 26373874 TI - Risk of extrapyramidal side effects comparing continuous vs. bolus intravenous metoclopramide administration: a systematic review and meta-analysis of randomised controlled trials. AB - AIMS AND OBJECTIVES: To provide evidence about whether intravenous metoclopramide continuous infusion is associated with fewer extrapyramidal side effects than bolus infusion. BACKGROUND: Many studies have described the effects produced by the administration of metoclopramide, as a continuous intravenous infusion or intravenous bolus directly, but there is a lack of consensus about the best administration of this drug to minimise extrapyramidal side effects. DESIGN: A meta-analysis was conducted. METHODS: The search data base was conducted in: Cochrane Library, PubMed, Web of Knowledge and Scopus, to collect randomised controlled trials examining the association between extrapyramidal side effects and intravenous metoclopramide continuous or bolus infusion. Meta-analyses were conducted for the eligible randomised controlled trials by Comprehensive Meta Analysis. Risk difference and 95% CIs were calculated with the Cochran's Q statistic, and heterogeneity was assessed with the I(2) test. RESULTS: Eleven randomised controlled trials were included. Meta-analysis showed that continuous intravenous infusion of metoclopramide produced less extrapyramidal side effects (8%; 95% CI, 5-11%; p < 0.001; I(2) = 65%). These improvements were particularly strong in studies scored >=3 in the Jadad scale (12%; 95% CI, 3-24%; I(2) = 0%), in emergency patients (12%; 95% CI, 2-25%; I(2) = 0%), in patients who used concomitant drugs (9%; 95% CI, 5-12%; I(2) = 80%) and when observation (8%; 95% CI, 5-14%; I(2) = 69%) or analogue scale (7%; 95% CI, 1-13%; I(2) = 64%) were used to quantify the number of extrapyramidal reactions in patients. CONCLUSIONS: Compared with bolus administration, continuous intravenous infusion of metoclopramide reduces the appearance of extrapyramidal side effects. RELEVANCE TO CLINICAL PRACTICE: Continuous infusion is an effective intervention to reduce in patients discomfort caused by the extrapyramidal side effects of metoclopramide. Clinicians also reduce the time spent on alleviating these unwanted effects. PMID- 26373876 TI - Copper-Catalyzed Cross-Coupling of Allylboronic Acids with alpha-Diazoketones. AB - Copper-catalyzed cross-coupling of substituted allylboronic acids with alpha diazoketones was studied. This allylation reaction is highly regioselective, providing the branched allylic product. The process involves creation of a new C(sp(3))-C(sp(3)) bond by retaining the keto functional group of the alpha diazoketone precursor. PMID- 26373875 TI - Bacillus endolithicus sp. nov., isolated from pebbles. AB - Strain JC267T was isolated from pebbles collected from Pingleshwar beach, Gujarat, India. Cells are Gram-stain-positive, facultatively anaerobic, non motile rods forming sub-terminal endospores in swollen ellipsoidal to oval sporangia. Strain JC267T contains anteiso-C15 : 0, iso-C15 : 0, iso-C14 : 0, iso C16 : 0, C16 : 0 and anteiso-C17 : 0 as major (>5 %) cellular fatty acids. Polar lipids include phosphatidylglycerol, phospholipids (PL1-3), glycolipids (GL1-2) and an unidentified lipid. Cell-wall amino acids are composed of diagnostic meso diaminopimelic acid, dl-alanine and a small amount of d-glutamic acid. The genomic DNA G+C content of strain JC267T is 45.5 mol%. The 16S rRNA gene sequence of strain JC267T showed highest sequence similarities of < 98.41 % with all species of the genus Bacillus when subjected to EzTaxon-e blast analysis. The reassociation values based on DNA-DNA hybridization of strain JC267T with Bacillus halosaccharovorans IBRC-M 10095T and Bacillus niabensis JCM 16399T were 26 +/- 1 % and 34 +/- 3 %, respectively. Based on taxonomic data obtained using a polyphasic approach, strain JC267T represents a novel species of the genus Bacillus, for which the name Bacillus endolithicus sp. nov. is proposed. The type strain is JC267T ( = IBRC-M 10914T = KCTC 33579T). PMID- 26373877 TI - Adaptation pathways of global wheat production: Importance of strategic adaptation to climate change. AB - Agricultural adaptation is necessary to reduce the negative impacts of climate change on crop yields and to maintain food production. However, few studies have assessed the course of adaptation along with the progress of climate change in each of the current major food producing countries. Adaptation pathways, which describe the temporal sequences of adaptations, are helpful for illustrating the timing and intensity of the adaptation required. Here we present adaptation pathways in the current major wheat-producing countries, based on sequential introduction of the minimum adaptation measures necessary to maintain current wheat yields through the 21st century. We considered two adaptation options: (i) expanding irrigation infrastructure; and (ii) switching crop varieties and developing new heat-tolerant varieties. We find that the adaptation pathways differ markedly among the countries. The adaptation pathways are sensitive to both the climate model uncertainty and natural variability of the climate system, and the degree of sensitivity differs among countries. Finally, the negative impacts of climate change could be moderated by implementing adaptations steadily according to forecasts of the necessary future adaptations, as compared to missing the appropriate timing to implement adaptations. PMID- 26373878 TI - Low vitamin D is linked to faster cognitive decline in older adults. PMID- 26373879 TI - Tri-chromatic white-light emission from a single-phase Ca9Sc(PO4)7:Eu(2+),Tb(3+),Mn(2+) phosphor for LED applications. AB - A series of single-phase Ca9Sc(PO4)7:Eu(2+),Tb(3+),Mn(2+) phosphors for UV excitations were synthesized by a high-temperature solid-state reaction. Energy transfer from Eu(2+)-> Tb(3+) and Eu(2+)-> Mn(2+) in a Ca9Sc(PO4)7 sample is a feasible route to realize color-tunable emission because Ca9Sc(PO4)7 single-doped Eu(2+)/Tb(3+)/Mn(2+) emit blue, green and red light, respectively. Most of the white light region in the CIE chromaticity diagram has been realized in Ca9Sc(PO4)7:Eu(2+),Tb(3+),Mn(2+) phosphors. Warm white light including the points of (0.337, 0.331), (0.353, 0.355) and (0.358, 0.327) close to day light (0.33, 0.33) with CCT of 5285 K, 4719 K and 4333 K is obtained, respectively. PMID- 26373880 TI - Supporting the callout for people first language in obesity. PMID- 26373882 TI - Genetic diversity and population structure of six Chinese indigenous pig breeds in the Taihu Lake region revealed by sequencing data. AB - The Chinese indigenous pig breeds in the Taihu Lake region are the most prolific pig breeds in the world. In this study, we investigated the genetic diversity and population structure of six breeds, including Meishan, Erhualian, Mi, Fengjing, Shawutou and Jiaxing Black, in this region using whole-genome SNP data. A high SNP with proportions of polymorphic markers ranging from 0.925 to 0.995 was exhibited by the Chinese indigenous pigs in the Taihu Lake region. The allelic richness and expected heterozygosity also were calculated and indicated that the genetic diversity of the Meishan breed was the greatest, whereas that of the Fengjing breed was the lowest. The genetic differentiation, as indicated by the fixation index, exhibited an overall mean of 0.149. Both neighbor-joining tree and principal components analysis were able to distinguish the breeds from each other, but structure analysis indicated that the Mi and Erhualian breeds exhibited similar major signals of admixture. With this genome-wide comprehensive survey of the genetic diversity and population structure of the indigenous Chinese pigs in the Taihu Lake region, we confirmed the rationality of the current breed classification of the pigs in this region. PMID- 26373883 TI - EPA-enriched phospholipids ameliorate cancer-associated cachexia mainly via inhibiting lipolysis. AB - Excessive loss of fat mass is considered as a key feature of body weight loss in cancer-associated cachexia (CAC). It affects the efficacy and tolerability of cancer therapy and reduces the quality and length of cancer patients' lives. The aim of the present study was to evaluate the effects of EPA-enriched phospholipids (EPA-PL) derived from starfish Asterias amurensis on cachectic weight loss in mice bearing S180 ascitic tumor, and TNF-alpha-stimulated lipolysis in 3T3-L1 adipocytes and to elucidate the possible mechanisms involved. Our findings revealed that oral administration of EPA-PL at 100 mg per kg body weight (BW) per day for 14 days prevented body weight loss in CAC mice by preserving the white adipose tissue (WAT) mass. We found that serum levels of nonesterified fatty acid (NEFA) and pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-alpha) and interleukin (IL)-6 increased in CAC mice but decreased significantly after oral treatment of EPA-PL. In addition, EPA-PL treatment also suppressed the overexpression of several key lipolytic factors and raised the mRNA levels of some adipogenic factors in the WAT of CAC mice. Moreover, treatment of EPA-PL (200 and 400 MUM) markedly inhibited TNF-alpha stimulated lipolysis in adipocytes. Furthermore, the antilipolytic effects of EPA PL were stimulated by the extracellular signal-regulated kinase 1/2 (ERK 1/2) inhibitor PD 98059 and blocked via the AMP-activated protein kinase (AMPK) inhibitor compound C and the phosphoinositide-3-kinase (PI3K) inhibitor LY 294002. Taken together, these data suggest that the dietary EPA-PL ameliorates CAC mainly via inhibiting lipolysis and at least in part for recovering the function of adipogenesis. PMID- 26373884 TI - Electronic Properties of MoS2-WS2 Heterostructures Synthesized with Two-Step Lateral Epitaxial Strategy. AB - Formation of heterojunctions of transition metal dichalcogenides (TMDs) stimulates wide interest in new device physics and technology by tuning optical and electronic properties of TMDs. TMDs heterojunctions are of scientific and technological interest for exploration of next generation flexible electronics. Herein, we report on a two-step epitaxial ambient-pressure CVD technique to construct in-plane MoS2-WS2 heterostructures. The technique has the potential to artificially control the shape and structure of heterostructures or even to be more potentially extendable to growth of TMD superlattice than that of one-step CVD technique. Moreover, the unique MX2 heterostructure with monolayer MoS2 core wrapped by multilayer WS2 is obtained by the technique, which is entirely different from MX2 heterostructures synthesized by existing one-step CVD technique. Transmission electron microscopy, Raman and photoluminescence mapping studies reveal that the obtained heterostructure nanosheets clearly exhibit the modulated structural and optical properties. Electrical transport studies demonstrate that the special MoS2 (monolayer)/WS2 (multilayer) heterojunctions serve as intrinsic lateral p-n diodes and unambiguously show the photovoltaic effect. On the basis of this special heterostructure, depletion-layer width and built-in potential, as well as the built-in electric field distribution, are obtained by KPFM measurement, which are the essential parameters for TMD optoelectronic devices. With further development in future studies, this growth approach is envisaged to bring about a new growth platform for two-dimensional atomic crystals and to create unprecedented architectures therefor. PMID- 26373887 TI - Tumour necrosis factor-alpha-induced protein 8 (TNFAIP8) expression associated with cell survival and death in cancer cell lines infected with canine distemper virus. AB - Oncolytic virotherapy is a novel strategy for treatment of cancer in humans and companion animals as well. Canine distemper virus (CDV), a paramyxovirus, has proven to be oncolytic through induction of apoptosis in canine-derived tumour cells, yet the mechanism behind this inhibitory action is poorly understood. In this study, three human mammary tumour cell lines and one canine-derived adenofibrosarcoma cell line were tested regarding to their susceptibility to CDV infection, cell proliferation, apoptosis, mitochondrial membrane potential and expression of tumour necrosis factor-alpha-induced protein 8 (TNFAIP8). CDV replication-induced cytopathic effect, decrease of cell proliferation rates, and >45% of infected cells were considered death and/or under late apoptosis/necrosis. TNFAIP8 and CDVM gene expression were positively correlated in all cell lines. In addition, mitochondrial membrane depolarization was associated with increase in virus titres (p < 0.005). Thus, these results strongly suggest that both human and canine mammary tumour cells are potential candidates for studies concerning CDV-induced cancer therapy. PMID- 26373886 TI - Donkey genome and insight into the imprinting of fast karyotype evolution. AB - The donkey, like the horse, is a promising model for exploring karyotypic instability. We report the de novo whole-genome assemblies of the donkey and the Asiatic wild ass. Our results reflect the distinct characteristics of donkeys, including more effective energy metabolism and better immunity than horses. The donkey shows a steady demographic trajectory. We detected abundant satellite sequences in some inactive centromere regions but not in neocentromere regions, while ribosomal RNAs frequently emerged in neocentromere regions but not in the obsolete centromere regions. Expanded miRNA families and five newly discovered miRNA target genes involved in meiosis may be associated with fast karyotype evolution. APC/C, controlling sister chromatid segregation, cytokinesis, and the establishment of the G1 cell cycle phase were identified by analysis of miRNA targets and rapidly evolving genes. PMID- 26373888 TI - Variation in antigen-antibody affinity among serotypes of Salmonella O4 serogroup, determined using specific antisera. AB - Serotyping is widely used for typing Salmonella during surveillance, and depends on determining the lipopolysaccharide (LPS) O-antigen and the flagellar protein (H-antigens) components. As the O-antigen is highly variable, and structurally unique to each serotype, we investigated the binding affinities of LPS from Salmonella serotypes of O4 serogroup with specific anti-antigen serum via immunoblot and enzyme-linked immunosorbent assays. Since the serotypes from O4 serogroup also express the O-antigen factor 12, O12 antiserum was also used for the analysis. LPS from the different serotypes showed different binding affinities with the antisera. Therefore, based on the antigen-antibody affinity, a modified agglutination assay was carried out by using O4 and O12 antisera. Although serotypes from O4 serogroup have the common O-antigen factors 4 and 12, the analysis showed that the degree of agglutination reaction is different for each of the serotypes. We suggest that Salmonella serogroup O4 serotypes exhibit different binding affinities with specific antisera despite the presence of common O-antigen factors 4 and 12. PMID- 26373890 TI - Stripe-like nanoscale structural phase separation in superconducting BaPb(1 x)Bi(x)O3. AB - The phase diagram of BaPb(1-x)Bi(x)O3 exhibits a superconducting dome in the proximity of a charge density wave phase. For the superconducting compositions, the material coexists as two structural polymorphs. Here we show, via high resolution transmission electron microscopy, that the structural dimorphism is accommodated in the form of partially disordered nanoscale stripes. Identification of the morphology of the nanoscale structural phase separation enables determination of the associated length scales, which we compare with the Ginzburg-Landau coherence length. We find that the maximum Tc occurs when the superconducting coherence length matches the width of the partially disordered stripes, implying a connection between the structural phase separation and the shape of the superconducting dome. PMID- 26373892 TI - A New Genus of Fleas with Associated Microorganisms in Dominican Amber. AB - A flea preserved in Dominican amber is described as Atopopsyllus cionus, n. gen., n. sp. (Atopopsyllini n. tribe, Spilopsyllinae, Pulicidae). The male specimen has two unique characters that have not been noted in previous extant or extinct fleas, thus warranting its tribal status. These characters are five-segmented maxillary palps and cerci-like organs on abdominal tergite X. Additional characters are the absence of ctenidia, very small eyes, a lanceolate terminal segment of the maxillary palps, legs with six notches on the dorsal margin of the tibiae, five pairs of lateral plantar bristles on the distitarsomeres, and nearly straight ungues with a wide space between the basal lobe and tarsal claw. Trypanosomes and coccobacilli in the rectum and coccobacilli on the tip of the epipharynx of the fossil are depicted and briefly characterized. PMID- 26373893 TI - Life History Traits and Demographic Parameters of Triatoma infestans (Hemiptera: Reduviidae) Fed on Human Blood. AB - Triatoma infestans (Klug, 1834) (Hemiptera: Reduviidae), the main vector of Chagas disease in South America, feeds primarily on humans, but ethical reasons preclude carrying out demographical studies using people. Thus, most laboratory studies of T. infestans are conducted using bird or mammal live hosts that may result in different demographic parameters from those obtained on human blood. Therefore, it is of interest to determine whether the use of an artificial feeder with human blood would be operational to rear triatomines and estimate population growth rates. We estimated life history traits and demographic parameters using an artificial feeder with human blood and compared them with those obtained on live hens. Both groups of T. infestans were kept under constant conditions [28 +/ 1 degrees C, 40 +/- 5% relative humidity, a photoperiod of 12:12 (L:D) h] and fed weekly. On the basis of age-specific survival and age-specific fecundity, we calculated the intrinsic rate of natural increase (r), the finite rate of population growth (lambda), the net reproductive rate (Ro), and the mean generation time (Tg). Our results show differences in life history traits between blood sources, resulting in smaller population growth rates on human blood than on live hens. Although demographic growth rate was smaller on human blood than on hens, it still remains positive, so the benefit/cost ratio of this feeding method seems relatively attractive. We discuss possibility of using the artificial feeder with human blood for both ecological and behavioral studies. PMID- 26373894 TI - Background-free in-vivo Imaging of Vitamin C using Time-gateable Responsive Probe. AB - Sensitive optical imaging of active biomolecules in the living organism requires both a molecular probe specifically responsive to the target and a high-contrast approach to remove the background interference from autofluorescence and light scatterings. Here, a responsive probe for ascorbic acid (vitamin C) has been developed by conjugating two nitroxide radicals with a long-lived luminescent europium complex. The nitroxide radical withholds the probe on its "off" state (barely luminescent), until the presence of vitamin C will switch on the probe by forming its hydroxylamine derivative. The probe showed a linear response to vitamin C concentration with a detection limit of 9.1 nM, two orders of magnitude lower than that achieved using electrochemical methods. Time-gated luminescence microscopy (TGLM) method has further enabled real-time, specific and background free monitoring of cellular uptake or endogenous production of vitamin C, and mapping of vitamin C in living Daphnia magna. This work suggests a rational design of lanthanide complexes for background-free small animal imaging of biologically functional molecules. PMID- 26373896 TI - Advagraf((r)) , a once-daily prolonged release tacrolimus formulation, in kidney transplantation: literature review and guidelines from a panel of experts. AB - The efficacy and safety of tacrolimus twice-a-day (BID) and once-a-day (QD) formulations are similar. However, the available information regarding the initiation and management of tacrolimus QD is sparse and practical information is lacking. A panel of French experts extensively reviewed the available literature on tacrolimus pharmacokinetics, clinical efficacy, and safety in kidney transplantation and, based on their own day-to-day experience, provided the practitioners with practical guidelines for the daily use and management of tacrolimus QD in de novo initiation or early conversion. PMID- 26373895 TI - Altered functioning of reward circuitry in youth offspring of parents with bipolar disorder. AB - BACKGROUND: Offspring of parents with bipolar disorder (BD) (BO) are at higher risk of BD than offspring of parents with non-BD psychopathology (NBO), although both groups are at higher risk than offspring of psychiatrically healthy parents (HC) for other affective and psychiatric disorders. Abnormal functioning in reward circuitry has been demonstrated previously in individuals with BD. We aimed to determine whether activation and functional connectivity in this circuitry during risky decision-making differentiated BO, NBO and HC. METHOD: BO (n = 29; mean age = 13.8 years; 14 female), NBO (n = 28; mean age = 13.9 years; 12 female) and HC (n = 23; mean age = 13.7 years; 11 female) were scanned while performing a number-guessing reward task. Of the participants, 11 BO and 12 NBO had current non-BD psychopathology; five BO and four NBO were taking psychotropic medications. RESULTS: A 3 (group) * 2 (conditions: win-control/loss-control) analysis of variance revealed a main effect of group on right frontal pole activation: BO showed significantly greater activation than HC. There was a significant main effect of group on functional connectivity between the bilateral ventral striatum and the right ventrolateral prefrontal cortex (Z > 3.09, cluster p < 0.05): BO showed significantly greater negative functional connectivity than other participants. These between-group differences remained after removing youth with psychiatric disorders and psychotropic medications from analyses. CONCLUSIONS: This is the first study to demonstrate that reward circuitry activation and functional connectivity distinguish BO from NBO and HC. The fact that the pattern of findings remained when comparing healthy BO v. healthy NBO v. HC suggests that these neuroimaging measures may represent trait-level neurobiological markers conferring either risk for, or protection against, BD in youth. PMID- 26373897 TI - A needs assessment in patient safety education for fourth-year medical students. PMID- 26373898 TI - Chemically Locked Bicelles with High Thermal and Kinetic Stability. AB - In situ polymerization of a bicellar mixture composed of a phospholipid and polymerizable surfactants afforded unprecedented stable bicelles. The polymerized composite showed an aligned phase over a wide thermal range (25 to >90 degrees C) with excellent (2)H quadrupole splitting of the solvent signal, thus implying versatility as an alignment medium for NMR studies. Crosslinking of the surfactants also brought favorable effects on the kinetic stability and alignment morphology of the bicelles. This system could thus offer a new class of scaffolds for biomembrane models. PMID- 26373900 TI - A novel mutation in two Hmong families broadens the range of STRA6-related malformations to include contractures and camptodactyly. AB - PDAC (also termed Matthew Wood) syndrome is a rare, autosomal recessive disorder characterized by pulmonary hypoplasia/aplasia, diaphragmatic defects, bilateral anophthalmia, and cardiac malformations. The disorder is caused by mutations in STRA6, an important regulator of vitamin A and retinoic acid metabolism. We describe six cases from four families of Hmong ancestry, seen over a 30 years period in California. These include: (i) consanguineous siblings with a combination of bilateral anophthalmia, diaphragmatic abnormalities, truncus arteriosus, and/or pulmonary agenesis/hypoplasia; (ii) a singleton fetus with bilateral anophthalmia, pulmonary agenesis, cardiac malformation, and renal hypoplasia; (iii) a sibling pair with a combination of antenatal contractures, camptodactyly, fused palpebral fissures, pulmonary agenesis, and/or truncus arteriosus; (iv) a fetus with bilateral anophthalmia, bushy eyebrows, pulmonary agenesis, heart malformation, and abnormal hand positioning. The phenotypic spectrum of PDAC syndrome has until now not included contractures or camptodactyly. Sequencing of STRA6 in unrelated members of families three and four identified a novel, shared homozygous splice site alteration (c.113 + 3_4delAA) that is predicted to be pathogenic. We hypothesize this may represent a unique disease allele in the Hmong. We also provide a focused review of all published PDAC syndrome cases with confirmed or inferred STRA6 mutations, illustrating the phenotypic and molecular variability that characterizes this disorder. PMID- 26373901 TI - Factor XII: a novel target for safe prevention of thrombosis and inflammation. AB - Plasma protein factor XII (FXII) activates the procoagulant and proinflammatory contact system that drives both the kallikrein-kinin system and the intrinsic pathway of coagulation. When zymogen FXII comes into contact with negatively charged surfaces, it auto-activates to the serine proteaseactivated FXII (FXIIa). Recently, various in vivo activators of FXII have been identified including heparin, misfolded protein aggregates, polyphosphate and nucleic acids. Murine models have established a central role of FXII in arterial and venous thrombosis. Despite its central function in thrombosis, deficiency in FXII does not impair haemostasis in animals and humans. In a preclinical cardiopulmonary bypass system in large animals, the FXIIa-blocking antibody 3F7 prevented thrombosis; however, in contrast to traditional anticoagulants, bleeding was not increased. In addition to its function in thrombosis, FXIIa initiates formation of the inflammatory mediator bradykinin. This mediator increases vascular leak, causes vasodilation, and induces chemotaxis with implications for septic, anaphylactic and allergic disease states. Therefore, targeting FXIIa appears to be a promising strategy for thromboprotection without associated bleeding risks but with anti inflammatory properties. PMID- 26373902 TI - Discriminative imaging of maternal and fetal blood flow within the placenta using ultrafast ultrasound. AB - Being able to map accurately placental blood flow in clinics could have major implications in the diagnosis and follow-up of pregnancy complications such as intrauterine growth restriction (IUGR). Moreover, the impact of such an imaging modality for a better diagnosis of placental dysfunction would require to solve the unsolved problem of discriminating the strongly intricated maternal and fetal vascular networks. However, no current imaging modality allows both to achieve sufficient sensitivity and selectivity to tell these entangled flows apart. Although ultrasound imaging would be the clinical modality of choice for such a problem, conventional Doppler echography both lacks of sensibility to detect and map the placenta microvascularization and a concept to discriminate both entangled flows. In this work, we propose to use an ultrafast Doppler imaging approach both to map with an enhanced sensitivity the small vessels of the placenta (~100 MUm) and to assess the variation of the Doppler frequency simultaneously in all pixels of the image within a cardiac cycle. This approach is evaluated in vivo in the placenta of pregnant rabbits: By studying the local flow pulsatility pixel per pixel, it becomes possible to separate maternal and fetal blood in 2D from their pulsatile behavior. Significance Statement: The in vivo ability to image and discriminate maternal and fetal blood flow within the placenta is an unsolved problem which could improve the diagnosis of pregnancy complications such as intrauterine growth restriction or preeclampsia. To date, no imaging modality has both sufficient sensitivity and selectivity to discriminate these intimately entangled flows. We demonstrate that Ultrafast Doppler ultrasound method with a frame rate 100x faster than conventional imaging solves this issue. It permits the mapping of small vessels of the placenta (~100 MUm) in 2D with an enhanced sensitivity. By assessing pixel-per-pixel pulsatility within single cardiac cycles, it achieves maternal and fetal blood flow discrimination. PMID- 26373904 TI - [Point of care ultrasound: why not?]. PMID- 26373903 TI - Associations of body composition measures and C2, a marker for small artery elasticity: The MESA. AB - OBJECTIVE: Lower C2, a continuous blood pressure waveform characteristic asserted to represent small artery elasticity, predicts future cardiovascular disease events. It is hypothesized that the paradoxical positive association between body mass index (BMI) and C2 may reflect muscle instead of excess fat. METHODS: In a multi-ethnic, community-living cohort of 1,960 participants, computed tomography scans of the abdomen were used to measure visceral adipose tissue (VAT) and total abdominal muscle tissue (TAMT), and applanation tonometry of the radial arteries was used to assess C2. The period cross-sectional associations between BMI, TAMT, and VAT with C2 were ascertained. RESULTS: The mean age was 62 +/- 9 years and 51% were male. After adjustments for age, gender, ethnicity, pack years smoking cigarettes, diabetes, hypertension, and total and HDL cholesterol, higher BMI (standardized beta = 0.09, P-value < 0.01) and more TAMT (standardized beta = 0.12, P-value < 0.01) were significantly associated with higher C2. In contrast, more VAT (standardized beta = -0.09, P-value < 0.01) was associated with lower C2. CONCLUSIONS: In multivariable analysis, VAT, in contrast to TAMT and BMI, was associated with less compliant small arteries. Visceral fat may be a better marker for detrimental excess body fat than BMI. PMID- 26373905 TI - [Cardiovascular drugs in aged and multimorbid patients]. AB - Cardiovascular diseases, such as arterial hypertension, heart failure, coronary artery disease, peripheral circulatory problems and atrial fibrillation are increasingly present in aged patients. Comorbidities, mainly diabetes, renal dysfunction, chronic bronchitis and degenerative joint diseases, are also frequent and need additional drug treatment. The usual polypharmacy often causes side effects due to overdosage and/or drug interactions. The main difficulty in choosing the proper therapeutic regimen consists in the lack of suitable dosing guidelines with adapted therapeutic targets for the older multimorbid population, usually not represented in the large controlled trials forming the basis of general recommendations. European guidelines for hypertension and heart failure are discussed as examples. PMID- 26373907 TI - [Echoscopy]. AB - The clinical use of pocket size ultrasound devices is still at an early stage. Its performance has been studied and proven in cardiology, gynecology, and gastroenterology. It is expected that the image quality will improve and that more techniques for miniaturized devices will be available in the near future. The perspective will be that more and more clinicians will have "echoscopes" as a bedside tool, replacing or complementary to a "stethoscope". The term "echoscopy" was defined by the European Federation of Societies of Ultrasound in Medicine and Biology (EFSUMB). Echoscopy is one form of point of care ultrasound (POCUS). Teaching material has been prepared by EFSUMB on how to use it (www.efsumb.org). PMID- 26373908 TI - [Ultrasound in thromboembolism]. AB - Imaging of pulmonary embolism (PTE) remains a great challange. Mortatity is even high. Possibilities of lung ultrasound, echocardiography, and compression leg vein sonography are discussed. Hemodynamic instable patients should achieve echocardiography at bed side with an accuracy of 90% and immeadiatly treated. In case of a suspected PTE, compression sonography of the leg veins is recommended. It can be performed within 2 min but, on average, yields a positive result in only one-half of the cases of PTE. During the last years, pulmonary sonography took root as a complementary method to MSCT either when the latter is not available or when it is contraindicated because of contrast agent allergy, renal insufficiency, or pregnancy. This method was able to provide evidence of subpleural pulmonary consolidations due to embolism in at least three-fourths of patients having a PTE. According to clinical presentation, combination of lung ultrasound, echocardiograpphy, and compression ultrasoud of the leg veins showed a sensitiviy of more than 90%. PMID- 26373909 TI - [Ultrasound: effective assistance in minor traumas]. AB - Ultrasound is ideal for rapid and reliable diagnosis in minor traumas. The diagnosis of fractures is eliminated or clearly made evident within real-time and with a painless, non-invasive method. Foreign bodies can be located and are clearly visible. The aetiology of a limping and coxalgia (specially in childhood) can often be diagnosed within short period of time. This article provides a brief outline. PMID- 26373910 TI - [Focused musculoskeletal sonography]. AB - Even in emergent situations, focused musculoskeletal sonography must not be overlooked. It has a place in traumatology no less valuable than its place in internal medicine. It can be used to identify traumatic joint effusions, occult fractures and fissures, joint inflammation, muscle and tendon rupture; it can differentiate soft tissue swelling, locate a foreign body, or identify the location of fractures. Focused ultrasound should be performed by the attending physician directly at the patient's bedside, in order to answer these specific questions. PMID- 26373911 TI - [Point of care ultrasound]. PMID- 26373912 TI - [Syncope]. PMID- 26373913 TI - [Renal artery stenosis: dilation no more effective than drug therapy alone]. PMID- 26373914 TI - [What happens after discontinuation of anticoagulation after unprovoked pulmonary embolism?]. PMID- 26373916 TI - [CME -EKG 50]. PMID- 26373918 TI - [Physician literature puzzle]. PMID- 26373919 TI - Current treatment of hypertension in patients with coronary artery disease recommended by different guidelines. AB - INTRODUCTION: It is important to know how to treat hypertension in patients with coronary artery disease (CAD). The reason for the review was to update this treatment and to discuss the 2015 American Heart Association/American College of Cardiology/American Society of Hypertension 2015 guidelines of treatment of hypertension in patients with CAD. AREAS COVERED: Studies between 1968 and 2015 were reviewed on treatment of hypertension in patients with CAD using a Medline search, and studies between 1977 and 2015 were reported. Hypertension should be treated with beta blockers and ACE inhibitors or angiotensin receptor blockers (ARBs). Long-acting nitrates are effective antianginal and anti-ischemic drugs. Calcium-channel blockers (CCBs) may be added if angina persists despite beta blockers and long-acting nitrates. The 2015 guidelines recommend that the blood pressure should be < 140/90 mm Hg in patients aged <= 80 years and the systolic blood pressure < 150 mm Hg if they are >= 80 years. EXPERT OPINION: Hypertension in patients with CAD should be treated with beta blockers and ACE inhibitors or ARBs. Long-acting nitrates are effective antianginal and anti-ischemic drugs. CCBs may be added if angina persists despite beta blockers and long-acting nitrates. The blood pressure should be < 140/90 mm Hg in patients aged < 80 years and the systolic blood pressure < 150 mm Hg if they are >= 80 years. PMID- 26373920 TI - Spinal Cord Stimulation (SCS) and Functional Magnetic Resonance Imaging (fMRI): Modulation of Cortical Connectivity With Therapeutic SCS. AB - INTRODUCTION: The neurophysiological basis of pain relief due to spinal cord stimulation (SCS) and the related cortical processing of sensory information are not completely understood. The aim of this study was to use resting state functional magnetic resonance imaging (rs-fMRI) to detect changes in cortical networks and cortical processing related to the stimulator-induced pain relief. METHODS: Ten patients with complex regional pain syndrome (CRPS) or neuropathic leg pain underwent thoracic epidural spinal cord stimulator implantation. Stimulation parameters associated with "optimal" pain reduction were evaluated prior to imaging studies. Rs-fMRI was obtained on a 3 Tesla, Philips Achieva MRI. Rs-fMRI was performed with stimulator off (300TRs) and stimulator at optimum (Opt, 300 TRs) pain relief settings. Seed-based analysis of the resting state functional connectivity was conducted using seeds in regions established as participating in pain networks or in the default mode network (DMN) in addition to the network analysis. NCUT (normalized cut) parcellation was used to generate 98 cortical and subcortical regions of interest in order to expand our analysis of changes in functional connections to the entire brain. We corrected for multiple comparisons by limiting the false discovery rate to 5%. RESULTS: Significant differences in resting state connectivity between SCS off and optimal state were seen between several regions related to pain perception, including the left frontal insula, right primary and secondary somatosensory cortices, as well as in regions involved in the DMN, such as the precuneus. In examining changes in connectivity across the entire brain, we found decreased connection strength between somatosensory and limbic areas and increased connection strength between somatosensory and DMN with optimal SCS resulting in pain relief. This suggests that pain relief from SCS may be reducing negative emotional processing associated with pain, allowing somatosensory areas to become more integrated into default mode activity. CONCLUSION: SCS reduces the affective component of pain resulting in optimal pain relief. Study shows a decreased connectivity between somatosensory and limbic areas associated with optimal pain relief due to SCS. PMID- 26373922 TI - Prediction of postoperative pain from assessment of pain induced by venous cannulation and propofol infusion. AB - BACKGROUND: Postoperative pain may lead to delayed mobilization, persisting pain, and psychosocial distress. There are no simple and reliable techniques for prediction of postoperative pain. This study was designed to evaluate if pain induced by venous cannulation or propofol injection can be used to predict postoperative pain. METHODS: This prospective study included 180 patients scheduled for laparoscopic cholecystectomy. Pain intensity associated with peripheral venous cannulation and administration of propofol preoperatively and pain intensity, and use of opioid postoperatively was recorded. RESULTS: Patients scoring cannulation-induced pain intensity > 2.0 VAS units were given postoperative opioid more often (65% vs. 36%; P < 0.001), earlier (12 min vs. 90 min; P < 0.001), and in higher doses (4.8 mg vs. 0 mg; P < 0.001), and also reported higher levels of postoperative pain intensity (5.8 vs. 2.9 VAS units; P < 0.001). There were also significant (P < 0.01) correlations with postoperative pain intensity (rs = 0.24), time to opioid administration (rs = -0.26), and total dose of opioid (rs = 0.25). Propofol-induced pain intensity correlated significantly (P < 0.05) with postoperative pain intensity (rs = 0.19). CONCLUSION: Pain intensity associated with venous cannulation and propofol infusion can easily be evaluated at bedside before surgery without specific equipment or training. Patients scoring > 2.0 VAS units on venous cannulation were found to have 3.4 times higher risk of postoperative pain after laparoscopic cholecystectomy. Low pain intensity associated with venous cannulation and propofol infusion indicate lower risk of postoperative pain. PMID- 26373924 TI - Acceptance. PMID- 26373925 TI - Serum calprotectin (S100A8/9): an independent predictor of ultrasound synovitis in patients with rheumatoid arthritis. AB - INTRODUCTION: Calprotectin, a heterodimeric complex of S100A8/9 (MRP8/14), has been proposed as an important serum biomarker that reflects disease activity and structural joint damage in rheumatoid arthritis (RA). The objective of this cross sectional study was to test the hypothesis that calprotectin is associated with clinical and ultrasound-determined disease activity in patients with RA. METHODS: A total of 37 patients with RA (including 24 females, a mean disease duration of 20 months) underwent a clinical examination and 7-joint ultrasound score (German US-7) of the clinically dominant hand and foot to assess synovitis by grey-scale (GS) and synovial vascularity by power Doppler (PD) ultrasound using semiquantitative 0-3 grading. The levels of serum calprotectin and C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were determined at the time of the ultrasound assessment. We analysed the relationship between serum calprotectin level, traditional inflammatory markers, and ultrasound-determined synovitis. RESULTS: The levels of serum calprotectin were significantly correlated with swollen joint count (r = 0.465, p < 0.005), DAS28-ESR (r = 0.430, p < 0.01), ESR (r = 0.370, p < 0.05) and, in particular, CRP (r = 0.629, p < 0.001). Calprotectin was significantly associated with GS (r = 0.359, p < 0.05) and PD synovitis scores (r = 0.497, p < 0.005). Using multivariate regression analysis, calprotectin, adjusted for age and sex, was a better predictor of PD synovitis score (R(2) = 0.765, p < 0.001) than CRP (R(2) = 0.496, p < 0.001). CONCLUSIONS: The serum levels of calprotectin are significantly associated with clinical, laboratory and ultrasound assessments of RA disease activity. These results suggest that calprotectin might be superior to CRP for monitoring ultrasound-determined synovial inflammation in RA patients. PMID- 26373926 TI - HPV.edu study protocol: a cluster randomised controlled evaluation of education, decisional support and logistical strategies in school-based human papillomavirus (HPV) vaccination of adolescents. AB - BACKGROUND: The National Human Papillomavirus (HPV) Vaccination Program in Australia commenced in 2007 for females and in 2013 for males, using the quadrivalent HPV vaccine (HPV 6,11,16,18). Thus far, we have demonstrated very substantial reductions in genital warts and in the prevalence of HPV among young Australian women, providing early evidence for the success of this public health initiative. Australia has a long history of school-based vaccination programs for adolescents, with comparatively high coverage. However, it is not clear what factors promote success in a school vaccination program. The HPV.edu study aims to examine: 1) student knowledge about HPV vaccination; 2) psycho-social outcomes and 3) vaccination uptake. METHODS/DESIGN: HPV.edu is a cluster randomised trial of a complex intervention in schools aiming to recruit 40 schools with year-8 enrolments above 100 students (approximately 4400 students). The schools will be stratified by Government, Catholic, and Independent sectors and geographical location, with up to 20 schools recruited in each of two states, Western Australia (WA) and South Australia (SA), and randomly allocated to intervention or control (usual practice). Intervention schools will receive the complex intervention which includes an adolescent intervention (education and distraction); a decisional support tool for parents and adolescents and logistical strategies (consent form returns strategies, in-school mop-up vaccination and vaccination-day guidelines). Careful process evaluation including an embedded qualitative evaluation will be undertaken to explore in depth possible mechanisms for any observed effect of the intervention on primary and secondary outcomes. DISCUSSION: This study is the first to evaluate the relative effectiveness of various strategies to promote best practice in school-based vaccination against HPV. The study aims to improve vaccination-related psychosocial outcomes, including adolescent knowledge and attitudes, decision making involvement, self-efficacy, and to reduce fear and anxiety. The study also aims to improve school vaccination program logistics including reduction in time spent vaccinating adolescents and increased number of consent forms returned (regardless of decision). Less anxiety in adolescents will likely promote more efficient vaccination, which will be more acceptable to teachers, nurses and parents. Through these interventions, it is hoped that vaccination uptake will be increased. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry, ACTRN12614000404628 , 14.04.2014. PMID- 26373927 TI - A proposed panel of biomarkers of healthy ageing. AB - BACKGROUND: There is no criterion reference for assessing healthy ageing and this creates difficulties when conducting and comparing research on ageing across studies. A cardinal feature of ageing is loss of function which translates into wide-ranging consequences for the individual and for family, carers and society. We undertook comprehensive reviews of the literature searching for biomarkers of ageing on five ageing-related domains including physical capability and cognitive, physiological and musculoskeletal, endocrine and immune functions. Where available, we used existing systematic reviews, meta-analyses and other authoritative reports such as the recently launched NIH Toolbox for assessment of neurological and behavioural function, which includes test batteries for cognitive and motor function (the latter described here as physical capability). We invited international experts to comment on our draft recommendations. In addition, we hosted an experts workshop in Newcastle, UK, on 22-23 October 2012, aiming to help capture the state-of-the-art in this complex area and to provide an opportunity for the wider ageing research community to critique the proposed panel of biomarkers. DISCUSSION: Here we have identified important biomarkers of healthy ageing classified as subdomains of the main areas proposed. Cardiovascular and lung function, glucose metabolism and musculoskeletal function are key subdomains of physiological function. Strength, locomotion, balance and dexterity are key physical capability subdomains. Memory, processing speed and executive function emerged as key subdomains of cognitive function. Markers of the HPA-axis, sex hormones and growth hormones were important biomarkers of endocrine function. Finally, inflammatory factors were identified as important biomarkers of immune function. We present recommendations for a panel of biomarkers that address these major areas of function which decline during ageing. This biomarker panel may have utility in epidemiological studies of human ageing, in health surveys of older people and as outcomes in intervention studies that aim to promote healthy ageing. Further, the inclusion of the same common panel of measures of healthy ageing in diverse study designs and populations may enhance the value of those studies by allowing the harmonisation of surrogate endpoints or outcome measures, thus facilitating less equivocal comparisons between studies and the pooling of data across studies. PMID- 26373928 TI - Single-molecule conductance in atomically precise germanium wires. AB - While the electrical conductivity of bulk-scale group 14 materials such as diamond carbon, silicon, and germanium is well understood, there is a gap in knowledge regarding the conductivity of these materials at the nano and molecular scales. Filling this gap is important because integrated circuits have shrunk so far that their active regions, which rely so heavily on silicon and germanium, begin to resemble ornate molecules rather than extended solids. Here we unveil a new approach for synthesizing atomically discrete wires of germanium and present the first conductance measurements of molecular germanium using a scanning tunneling microscope-based break-junction (STM-BJ) technique. Our findings show that germanium and silicon wires are nearly identical in conductivity at the molecular scale, and that both are much more conductive than aliphatic carbon. We demonstrate that the strong donor ability of C-Ge sigma-bonds can be used to raise the energy of the anchor lone pair and increase conductance. Furthermore, the oligogermane wires behave as conductance switches that function through stereoelectronic logic. These devices can be trained to operate with a higher switching factor by repeatedly compressing and elongating the molecular junction. PMID- 26373923 TI - Discordant identification of pediatric severe sepsis by research and clinical definitions in the SPROUT international point prevalence study. AB - INTRODUCTION: Consensus criteria for pediatric severe sepsis have standardized enrollment for research studies. However, the extent to which critically ill children identified by consensus criteria reflect physician diagnosis of severe sepsis, which underlies external validity for pediatric sepsis research, is not known. We sought to determine the agreement between physician diagnosis and consensus criteria to identify pediatric patients with severe sepsis across a network of international pediatric intensive care units (PICUs). METHODS: We conducted a point prevalence study involving 128 PICUs in 26 countries across 6 continents. Over the course of 5 study days, 6925 PICU patients <18 years of age were screened, and 706 with severe sepsis defined either by physician diagnosis or on the basis of 2005 International Pediatric Sepsis Consensus Conference consensus criteria were enrolled. The primary endpoint was agreement of pediatric severe sepsis between physician diagnosis and consensus criteria as measured using Cohen's kappa. Secondary endpoints included characteristics and clinical outcomes for patients identified using physician diagnosis versus consensus criteria. RESULTS: Of the 706 patients, 301 (42.6%) met both definitions. The inter-rater agreement (kappa +/- SE) between physician diagnosis and consensus criteria was 0.57 +/- 0.02. Of the 438 patients with a physician's diagnosis of severe sepsis, only 69% (301 of 438) would have been eligible to participate in a clinical trial of pediatric severe sepsis that enrolled patients based on consensus criteria. Patients with physician-diagnosed severe sepsis who did not meet consensus criteria were younger and had lower severity of illness and lower PICU mortality than those meeting consensus criteria or both definitions. After controlling for age, severity of illness, number of comorbid conditions, and treatment in developed versus resource-limited regions, patients identified with severe sepsis by physician diagnosis alone or by consensus criteria alone did not have PICU mortality significantly different from that of patients identified by both physician diagnosis and consensus criteria. CONCLUSIONS: Physician diagnosis of pediatric severe sepsis achieved only moderate agreement with consensus criteria, with physicians diagnosing severe sepsis more broadly. Consequently, the results of a research study based on consensus criteria may have limited generalizability to nearly one-third of PICU patients diagnosed with severe sepsis. PMID- 26373930 TI - Peri-operative complications and hematologic improvement after first-line splenectomy for splenic marginal zone lymphoma. PMID- 26373929 TI - The differential effects of leukocyte-containing and pure platelet-rich plasma (PRP) on tendon stem/progenitor cells - implications of PRP application for the clinical treatment of tendon injuries. AB - INTRODUCTION: Platelet-rich plasma (PRP) is widely used to treat tendon injuries in clinics. These PRP preparations often contain white blood cells or leukocytes, and the precise cellular effects of leukocyte-rich PRP (L-PRP) on tendons are not well defined. Therefore, in this study, we determined the effects of L-PRP on tendon stem/progenitor cells (TSCs), which play a key role in tendon homeostasis and repair. METHODS: TSCs isolated from the patellar tendons of rabbits were treated with L-PRP or P-PRP (pure PRP without leukocytes) in vitro, followed by measuring cell proliferation, stem cell marker expression, inflammatory gene expression, and anabolic and catabolic protein expression by using immunostaining, quantitative real-time polymerase chain reaction, Western blot, and enzyme-linked immunosorbent assay, respectively. RESULTS: Cell proliferation was induced by both L-PRP and P-PRP in a dose-dependent manner with maximum proliferation at a 10 % PRP dose. Both PRP treatments also induced differentiation of TSCs into active tenocytes. Nevertheless, the two types of PRP largely differed in several effects exerted on TSCs. L-PRP induced predominantly catabolic and inflammatory changes in differentiated tenocytes; its treatment increased the expression of catabolic marker genes, matrix metalloproteinase-1 (MMP-1), MMP-13, interleukin-1beta (IL-1beta), IL-6 and tumor necrosis factor alpha (TNF-alpha), and their respective protein expression and prostaglandin E2 (PGE 2) production. In contrast, P-PRP mainly induced anabolic changes; that is, P-PRP increased the gene expression of anabolic genes, alpha-smooth muscle actin (alpha-SMA), collagen types I and III. CONCLUSIONS: These findings indicate that, while both L-PRP and P-PRP appear to be "safe" in inducing TSC differentiation into active tenocytes, L-PRP may be detrimental to the healing of injured tendons because it induces catabolic and inflammatory effects on tendon cells and may prolong the effects in healing tendons. On the other hand, when P-PRP is used to treat acutely injured tendons, it may result in the formation of excessive scar tissue due to the strong potential of P-PRP to induce inordinate cellular anabolic effects. PMID- 26373932 TI - Founder of Leg Club model awarded Order of the British Empire in recent Queen's Birthday Honours. PMID- 26373931 TI - Polymorphism profiling of nine high altitude relevant candidate gene loci in acclimatized sojourners and adapted natives. AB - BACKGROUND: Sea level sojourners, on ascent to high altitude, undergo acclimatization through integrated physiological processes for defending the body against oxygen deprivation while the high altitude natives (resident population) are adapted to the prevailing hypobaric hypoxic condition through natural selection. Separating the acclimatization processes from adaptive changes and identifying genetic markers in lowlanders that may be beneficial for offsetting the high altitude hypoxic stress, although challenging, is worth investigating. We genotyped nine candidate gene polymorphisms, suggested to be relevant in high altitude environment, in sea level acclimatized sojourners and adapted natives for understanding differences/commonality between the acclimatized and the adapted cohorts at the genetic level. RESULTS: Statistically similar genotypic and allelic frequencies were observed between the sea level sojourners (acclimatized) and the high altitude natives (adapted) in six loci viz., EDN1 (endothelin 1) -3A/-4A VNTR, ADRB2 (beta-2 adrenergic receptor, surface) Arg16Gly (rs1042713:A > G), ADRB3 (beta-3 adrenergic receptor) Trp64Arg (rs4994:T > C), eNOS (nitric oxide synthase, endothelial) Glu298Asp (rs1799983:T > G), TH (tyrosine hydroxylase) Val81Met (rs6356:G > A) and VEGF (vascular endothelial growth factor) 963C > T (rs3025039:C > T) while SCNN1B (amiloride-sensitive sodium channel, subunit beta) Thr594Met (rs1799979:C > T) was monomorphic. Genotypic and allelic frequencies in EDN1 9465G > A (rs2071942:G > A) and ADRB2 Gln27Glu (rs1042714:G > C) were significantly different between the acclimatized sojourners and the high altitude natives with higher frequency of GG and GA genotypes of EDN1 rs2071942 and CC genotype of ADRB2 rs1042714 being observed in Ladakh natives. Mutated A allele (AA genotype) of rs2071942 and carriers of G allele (GG + GC genotypes) of rs1042714 were less favorable during acclimatization under recessive and dominant genetic models of inheritance respectively indicating thereby that GG genotype and G allele of EDN1 rs2071942 and CC genotype of ADRB2 rs1042714 conferred acclimatization benefit. CONCLUSION: Sea level acclimatized individuals shared similarity with the adapted natives in certain high altitude relevant genetically based trait variation suggesting advantageous consequence as well as commonality in gene regulatory pathways in which these gene products function both during process of acclimatization and adaptation in high altitude environment. PMID- 26373935 TI - Stimulus Frequency Otoacoustic Emission Delays and Generating Mechanisms in Guinea Pigs, Chinchillas, and Simulations. AB - According to coherent reflection theory (CRT), stimulus frequency otoacoustic emissions (SFOAEs) arise from cochlear irregularities coherently reflecting energy from basilar membrane motion within the traveling-wave peak. This reflected energy arrives in the ear canal predominantly with a single delay at each frequency. However, data from humans and animals indicate that (1) SFOAEs can have multiple delay components, (2) low-frequency SFOAE delays are too short to be accounted for by CRT, and (3) "SFOAEs" obtained with a 2nd ("suppressor") tone >=2 octaves above the probe tone have been interpreted as arising from the area basal to the region of cochlear amplification. To explore these issues, we collected SFOAEs by the suppression method in guinea pigs and time-frequency analyzed these data, simulated SFOAEs, and published chinchilla SFOAEs. Time frequency analysis revealed that most frequencies showed only one SFOAE delay component while other frequencies had multiple components including some with short delays. We found no systematic patterns in the occurrence of multiple delay components. Using a cochlear model that had significant basilar membrane motion only in the peak region of the traveling wave, simulated SFOAEs had single and multiple delay components similar to the animal SFOAEs. This result indicates that multiple components (including ones with short delays) can originate from cochlear mechanical irregularities in the SFOAE peak region and are not necessarily indicative of SFOAE sources in regions >=2 octaves basal of the SFOAE peak region. We conclude that SFOAEs obtained with suppressors close to the probe frequency provide information primarily about the mechanical response in the region that receives amplification, and we attribute the too-short SFOAE delays at low frequencies to distortion-source SFOAEs and coherent reflection from multiple cochlear motions. Our findings suggest that CRT needs revision to include reflections from multiple motions in the cochlear apex. PMID- 26373936 TI - Correlations Between Pitch and Phoneme Perception in Cochlear Implant Users and Their Normal Hearing Peers. AB - This study examined correlations between pitch and phoneme perception for nine cochlear implant users and nine normal hearing listeners. Pure tone frequency discrimination thresholds were measured for frequencies of 500, 1000, and 2000 Hz. Complex tone fundamental frequency (F0) discrimination thresholds were measured for F0s of 110, 220, and 440 Hz. The effects of amplitude and frequency roving were measured under the rationale that individuals who are robust to such perturbations would perform better on phoneme perception measures. Phoneme identification was measured using consonant and vowel materials in quiet, in stationary speech-shaped noise (SSN), in spectrally notched SSN, and in temporally gated SSN. Cochlear implant pure tone frequency discrimination thresholds ranged between 1.5 and 9.9 %, while cochlear implant complex tone F0 discrimination thresholds ranged between 2.6 and 28.5 %. On average, cochlear implant users had 5.3 dB of masking release for consonants and 8.4 dB of masking release for vowels when measured in temporally gated SSN compared to stationary SSN. Correlations with phoneme identification measures were generally higher for complex tone discrimination measures than for pure tone discrimination measures. Correlations with phoneme identification measures were also generally higher for pitch perception measures that included amplitude and frequency roving. The strongest correlations were observed for measures of complex tone F0 discrimination with phoneme identification in temporally gated SSN. The results of this study suggest that musical training or signal processing strategies that improve F0 discrimination should improve consonant identification in fluctuating noise. PMID- 26373939 TI - Editorial: Translational Neuroscience: Narrowing Distances for Future Discoveries. PMID- 26373937 TI - Transcriptome profiling of postharvest strawberry fruit in response to exogenous auxin and abscisic acid. AB - MAIN CONCLUSION: Auxin and abscisic acid regulate strawberry fruit ripening and senescence through cross-talk of their signal transduction pathways that further modulate the structural genes related to physico-chemical properties of fruit. The physiological and transcriptomic changes in harvested strawberry fruits in responses to IAA, ABA and their combination were analyzed. Exogenous IAA delayed the ripening process of strawberries after harvest while ABA promoted the postharvest ripening. However, treatment with a combination of IAA and ABA did not slow down nor accelerate the postharvest ripening in the strawberry fruits. At the molecular level, exogenous IAA up regulated the expressions of genes related to IAA signaling, including AUX/IAA, ARF, TOPLESS and genes encoding E3 ubiquitin protein ligase and annexin, and down regulated genes related to pectin depolymerization, cell wall degradation, sucrose and anthocyanin biosyntheses. In contrast, exogenous ABA induced genes related to fruit softening, and genes involved in signaling pathways including SKP1, HSPs, CK2, and SRG1. Comparison of transcriptomes in responses to individual treatments with IAA or ABA or the combination revealed that there were cooperative and antagonistic actions between IAA and ABA in fruit. However, 17% of the differentially expressed unigenes in response to the combination of IAA and ABA were unique and were not found in those unigenes responding to either IAA or ABA alone. The analyses also found that receptor-like kinases and ubiquitin ligases responded to both IAA and ABA, which seemed to play a pivotal role in both hormones' signaling pathways and thus might be the cross-talk points of both hormones. PMID- 26373941 TI - Stabilization of Chromobacterium viscosum Lipase (CVL) Against Ultrasound Inactivation by the Pretreatment with Polyethylene Glycol (PEG). AB - Although ultrasound has been used to accelerate many enzymatic reactions, the low stability of enzymes in such a system still remains a critical issue, limiting its industrial application. Here, we have reported that polyethylene glycol (PEG) pretreatment stabilized Chromobacterium viscosum lipase (CVL) in ultrasound assisted water-isooctane emulsion. PEGs of different molecular weights and concentrations were used to pretreat CVL, and the pretreated lipase activities for olive oil hydrolysis were investigated at different ultrasonic powers. The best result was attained with PEG400 at 100 mg/ml for a lipase concentration of 0.02 mg/ml and an ultrasonic power of 106 W. The half-life time of PEG400-treated lipase at 106 W was 54 min, a 27-fold higher than that attained using untreated lipase. Circular dichroism (CD) spectra suggested that PEG increased the rigidity of CVL structure, which favored the lipase stability against ultrasound inactivation. These results have important implications for the exploitation of ultrasound in biocatalytic process. PMID- 26373940 TI - Expression and characterization of a new thermostable esterase from Clostridium thermocellum. AB - The thermostable esterase from the thermophilic bacterium Clostridium thermocellum DSM 1313 was expressed in Escherichia coli and purified by Ni(2+) affinity chromatography. Its molecular weight was approximately 35 kDa according to 12 % sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis. The enzyme exhibited the highest specific activity with p-nitrophenyl butyrate (285 s(-1) mM(-1)). The activity of the esterase was greatest at 65 degrees C, and the esterase maintained residual activity levels of 70 and 50 % after 3 h incubation at 65 and 70 degrees C, respectively. Its activity was optimal at pH 7.0, was enhanced in the presence of Ca(2+) and Mg(2+), and was inhibited by Ni(2+) and Cu(2+). The addition of surfactants, such as Tween-20, Tween-80, Triton X-100, and SDS, at concentrations of 5 % (v/v) significantly inhibited the lipolytic action of the esterase. Enzyme activity was relatively stable in 10 % methanol, and 50 % residual activity was seen in 10 % DMSO, demonstrating its potential in biodiesel production and industrial applications. PMID- 26373942 TI - Effects of enzyme loading, densification, and storage on AFEX-pretreated biomass for ethanol production. AB - Corn stover, switchgrass, and prairie cordgrass were treated with an ammonia fiber expansion (AFEX) process and a novel densification method (ComPAKco). Separate hydrolysis and fermentation (SHF) and simultaneous saccharification and fermentation (SSF) were used to evaluate impacts of densification. ComPAKco densification is characterized by low-temperature and low-energy requirements, resulting in compacted biomass briquettes (CBB) 1-2 cm square, with a bulk density of 380-460 kg/m(3). Feedstocks were evaluated before and following AFEX pretreatment, after densification, and after storage. Two enzyme doses were tested. The low rate used 5 filter paper units (FPU) of Spezyme CP (cellulase) and 21.3 cellobiase units (CBU) of Novozyme 188 (aka NS50010 [beta-glucosidase]) per gram of glucan. The high dosage rate was three times higher and resulted in 40-56 % and 33-82 % higher ethanol yields with SHF and SSF, respectively. Trials revealed no adverse effect on ethanol yield following densification or 6-month storage of densified, AFEX-pretreated feedstocks. PMID- 26373943 TI - Production and characterization of surfactin-type lipopeptides as bioemulsifiers produced by a Pinctada martensii-derived Bacillus mojavensis B0621A. AB - Bacillus mojavensis B0621A was isolated from the mantle of a pearl oyster Pinctada martensii collected from South China Sea. Semi-purified surfactins (225 mg L(-1)) were obtained by acid precipitation and vacuum flash chromatography. The component of the semi-purified surfactins was preliminarily analyzed by liquid chromatography mass spectrometer system, and the results showed that all these surfactins could be a group of homologues. Eight surfactin homologues were isolated and afforded by reversed phase high-performance liquid chromatography. Furthermore, their structure was characterized by mass spectrometry analysis combined with nuclear magnetic resonance spectroscopy techniques. These surfactins shared seven amino acids as peptide backbone and a saturated beta hydroxy fatty acid chain residue (from C13 to C15), differed each other from peptide sequence in the position of Leu7 or Val7. All these surfactins had significant activity and stability of emulsification under various pH (from 7.0 to 12.0), temperature range (from 20 to 115 degrees C) and sodium chloride concentration (from 2.5 to 20.0 %, w/v). Taken all together, these results indicated that B. mojavensis B0621A have potential to be an alternative source as a biological-derived emulsifying agent. PMID- 26373944 TI - Molecular Characterization and Antibacterial Activity Analysis of Two Novel Penaeidin Isoforms from Pacific White Shrimp, Litopenaeus vannamei. AB - Penaeidins were important immunity effector molecules, which played a crucial role in innate immunity system of penaeid shrimp. Here, we reported two penaeidin isoforms from Litopenaeus vannamei, which were named as Lva-PEN 2 and Lva-PEN 3 according to the respective structure features. The results of amino acid sequence multiple alignments showed that high similarities existed among these penaeidins. A signal peptide sequence and a cysteine-rich domain which contained six cysteine amino acid residues existed in each penaeidin at the same time. Besides, there was a proline-rich motif which was composed of eight proline residues existed in each penaeidin. After the expression profile analysis was studied, we found that both Lva-pen 2 and Lva-pen 3 transcripts were up-regulated at 48 h after bacteria challenge. Except for the antibacterial activity against Gram-positive bacteria like other penaeidins, these two penaeidins could strongly bind to bacteria and possessed antiproteinase activity. It was speculated that these two penaeidins could prevent bacteria pervasion through bacteria-binding activity and antiproteinase activity. Meantime, the proline-rich motif played a crucial role in these biological processes. PMID- 26373945 TI - Simultaneous Removal of Phenol and Dissolved Solids from Wastewater Using Multichambered Microbial Desalination Cell. AB - Microbial desalination cell (MDC) has great potential toward direct electricity generation from wastewater and concurrent desalination through potential difference developed due to microbial activity. Degradation of phenol by isolate Pseudomonas aeruginosa in anodic chamber and simultaneous desalination of water in middle desalination chamber of multichamber MDC is demonstrated in this study. Performance of the MDCs with different anodic inoculum conditions, namely pure culture of P. aeruginosa (MDC-1), 50 % v/v mixture of P. aeruginosa and anaerobic mixed consortia (MDC-2) and anaerobic mixed consortia (MDC-3), was evaluated to compare the phenol degradation in anodic chamber, bioelectricity generation, and simultaneous total dissolved solids (TDS) removal from saline water in desalination chamber. Synergistic effect between P. aeruginosa and mixed anaerobic consortia as inoculum was evident in MDC-2 demonstrating phenol degradation of 90 %, TDS removal of 75 % in 72 h of reaction time along with higher power generation of 27.5 mW/m(2) as compared to MDC-1 (95 %, 64 %, 12.8 mW/m(2), respectively) and MDC-3 (58 %, 52 %, 4.8 mW/m(2), respectively). The results illustrate that the multichamber MDC-2 is effective for simultaneous removal of phenol and dissolved solids contained in industrial wastewaters. PMID- 26373947 TI - Current status and future perspectives of PSMA-targeted therapy in Europe: opportunity knocks. PMID- 26373946 TI - Doping with anabolic androgenic steroids (AAS): Adverse effects on non reproductive organs and functions. AB - Since the 1970s anabolic androgenic steroids (AAS) have been abused at ever increasing rates in competitive athletics, in recreational sports and in bodybuilding. Exceedingly high doses are often consumed over long periods, in particular by bodybuilders, causing acute or chronic adverse side effects frequently complicated by additional polypharmacy. This review summarizes side effects on non-reproductive organs and functions; effects on male and female reproduction have been recently reviewed in a parallel paper. Among the most striking AAS side effects are increases in haematocrit and coagulation causing thromboembolism, intracardiac thrombosis and stroke as well as other cardiac disturbances including arrhythmias, cardiomyopathies and possibly sudden death. 17alpha-alkylated AAS are liver toxic leading to cholestasis, peliosis, adenomas and carcinomas. Hyperbilirubinaemia can cause cholemic nephrosis and kidney failure. AAS abuse may induce exaggerated self-confidence, reckless behavior, aggressiveness and psychotic symptoms. AAS withdrawal may be accompanied by depression and suicidal intentions. Since AAS abuse is not or only reluctantly admitted physicians should be aware of the multitude of serious side effects when confronted with unclear symptoms. PMID- 26373949 TI - 4-Hydroxyphenacyl Ammonium Salts: A Photoremovable Protecting Group for Amines in Aqueous Solutions. AB - Irradiation of N-protected p-hydroxyphenacyl (pHP) ammonium caged derivatives at 313 nm releases primary and secondary amines or ammonia in nearly quantitative yields via the photo-Favorskii reaction when conducted in acidic or neutral aqueous buffered media. The reaction efficiencies are strongly dependent on the pH with the most efficient and highest yields obtained when the pH of the media maintains the ammonium and p-hydroxyl groups as their conjugate acids. For example, the overall quantum yields of simple secondary amines release are 0.5 at acidic pH from 3.9 to 6.6 dropping to 0.1 at neutral pH 7.0 and 0.01 at pH 8.4. Speciation studies provide an acid-base profile that helps define the scope and limitations of the reaction. When the pKa of the ammonium group is lower than that of the phenolic hydroxyl group, as is the case for the alpha-amino-protected amino acids, the more acidic ammonium ion deprotonates as the media pH is changed from acidic toward neutral or basic, thus diminishing the leaving group ability of the amino group. This, in turn, lowers the propensity for the photo-Favorskii rearrangement reaction to occur and opens the reaction pathway to alternative competing photoreduction process. PMID- 26373948 TI - Improving the stability of chitosan-gelatin-based hydrogels for cell delivery using transglutaminase and controlled release of doxycycline. AB - Although local cell delivery is an option to repair tissues, particularly using chitosan-based hydrogels, significant attrition of injected cells prior to engraftment has been a problem. To address this problem, we explored the possibility of stabilizing the chitosan-gelatin (CG) injectable hydrogels using (1) controlled release of doxycycline (DOX) to prevent premature degradation due to increased gelatinase activity (MMP-2 and MMP-9), and (2) transglutaminase (TG) to in situ cross-link gelatin to improve the mechanical stability. We prepared DOX-loaded PLGA nanoparticles, loaded into the CG hydrogels, measured DOX release for 5 days, and modeled using a single-compartmental assumption. Next, we assessed the influence of TG and DOX on hydrogel compression properties by incubating hydrogels for 7 days in PBS. We evaluated the effect of these changes on retention of fibroblasts and alterations in MMP-2/MMP-9 activity by seeding 500,000 fibroblasts for 5 days. These results showed that 90 % of DOX released from cross-linked CG hydrogels after 4 days, unlike CG hydrogels where 90 % of DOX was released within the first day. Addition of TG enhanced the CG hydrogel stability significantly. More than 60 % of seeded fibroblasts were recovered from the CG-TG hydrogels at day 5, unlike 40 % recovered from CG-hydrogels. Inhibition of MMP-2/MMP-9 were observed. In summary, controlled release of DOX from CG hydrogels cross-linked with TG shows a significant potential as a carrier for cell delivery. PMID- 26373950 TI - Erratum to: Barth syndrome without tetralinoleoyl cardiolipin deficiency: a possible ameliorated phenotype. PMID- 26373951 TI - Nervous system involvement in Farber disease. AB - A 30 months-old boy with Farber disease developed nystagmus 12 months after hematopoietic stem cell transplantation (HSCT). At 40 months, gait ataxia was evident, and brain MRI showed increased size of pericerebellar sulci and 4th ventricle. EMG showed denervation in the tongue and upper limb muscles, consistent with motor neuron disease. HSCT improves the peripheral manifestations of Farber disease, but may not prevent the progressive neurological deterioration. PMID- 26373952 TI - Molecular genetic studies on EGFR, KRAS, BRAF, ALK, PIK3CA, PDGFRA, and DDR2 in primary pulmonary adenoid cystic carcinoma. AB - BACKGROUND: Pulmonary adenoid cystic carcinoma (PACC) is an uncommon neoplasm of the lung but represents the predominant type of salivary gland-type lung carcinoma. Only a few studies have focused on the genetic events associated with PACC. The aim of this study was to characterize the genetic events associated with PACC. FINDINGS: We reviewed 24 cases of primary PACC between 2000 and 2014, including 21 cases reported in our previous study and three new cases added in 2014. Mutation profiling of the EGFR, KRAS, BRAF, ALK, PIK3CA, PDGFRA, and DDR2 genes was performed using next-generation sequencing, Sanger sequencing, and quantitative polymerase chain reaction in 9 successfully amplified cases. The 24 cases of PACC included 7 men and 17 women, aged 24-74 years (mean, 50.8 years). All the cases were located in the trachea or bronchus. No mutations were detected in any of the seven genes in the nine cases that qualified for mutation analysis, and the results using different methods were consistent. CONCLUSIONS: The data presented in this work suggest that EGFR, KRAS, BRAF, ALK, PIK3CA, PDGFRA, and DDR2 may not be driver genes in primary pulmonary adenoid cystic carcinoma. PMID- 26373953 TI - Reduction in amino-acid-induced anti-hypothermic effects during general anesthesia in ovariectomized rats with progesterone replacement. AB - PURPOSE: The aim of the present study was to determine whether the ovarian hormones, estrogen and progesterone, had different influences on amino-acid induced anti-hypothermic effects during general anesthesia. METHODS: Ovariectomized Sprague-Dawley female rats were divided into four groups: those administered 17beta-estradiol plus saline or an amino acid mixture (E2-Sal and E2 AA, respectively) and progesterone plus saline or an amino acid mixture (P-Sal and P-AA, respectively). Five weeks after ovariectomy, rats were given either E2 or P and then administered either Sal or AA solution for 180 min during anesthesia with sevoflurane. Rectal temperatures were measured. RESULTS: Rectal temperatures were significantly higher in the E2-AA group than in the E2-Sal group 165 and 180 min after initiating the infusion of the test solutions. However, no significant differences were observed between the P-treated groups. The phosphorylation of 4E-BP1 and S6K1 was significantly greater in the E2-AA group than in the E2-Sal group (P < 0.05, P < 0.001, respectively). In contrast, the phosphorylation of 4E-BP1 was significantly lower in the P-AA group than in the P-Sal group (P < 0.001). CONCLUSIONS: These results suggest that progesterone reduces amino-acid-induced anti-hypothermic effects during general anesthesia. PMID- 26373954 TI - The possible involvement of JNK activation in the spinal dorsal horn in bortezomib-induced allodynia: the role of TNF-alpha and IL-1beta. AB - PURPOSE: Bortezomib (BTZ), a widely used chemotherapeutic drug, is closely associated with the development of painful peripheral neuropathy, but the mechanism underlying the induction of this disorder by BTZ remains largely unclear. To examine this association, we have evaluated the activation of mitogen activated protein kinase (MAPK) family members in the spinal dorsal horn and the role of tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1beta) in BTZ-induced allodynia in rats. METHODS: Male Sprague-Dawley rats were used as the model animals. The paw withdrawal test, in which mechanical stimuli (von Frey hairs) is applied to the plantar surface of the hindpaw, was used to determine any changes in the paw withdrawal threshold of the treated rats. A PE-10 catheter was placed intrathecally to deliver TNF-alpha neutralizing antibody, IL-1 receptor antagonist (IL-1ra) or the c-Jun N-terminal kinase (JNK) inhibitor SP600125. The mRNA levels of various cytokines were measured by real-time quantitative PCR. The expression of TNF-alpha, IL-1beta and mitogen-activated protein kinase (MAPK) family members in the spinal dorsal horn was measured by western blot analysis and immunohistochemistry. All data were expressed as the mean +/- standard error of the mean and analyzed using the SPSS version 13.0 software program. RESULTS: The BTZ treatment induced an upsurge in the mRNA and protein levels of TNF-alpha in the neurons and IL-1beta in the astrocytes in the spinal dorsal horn. It also significantly upregulated the phosphorylation of JNK but not of extracellular signal-regulated kinases (ERK) and p38-MAPK in astrocytes of the spinal dorsal horn. Inhibition of TNF-alpha or IL-1beta ameliorated JNK activation and mechanical allodynia induced by BTZ. Co administration of thalidomide (TNF-alpha synthesis inhibitor) and IL-1ra prevented BTZ-induced mechanical allodynia. CONCLUSION: Our results suggest that the TNF-alpha or IL-1beta/JNK pathway in the spinal dorsal horn may play a critical role in the development of painful peripheral neuropathy induced by BTZ. PMID- 26373955 TI - HAROW: the first comprehensive prospective observational study comparing treatment options in localized prostate cancer. AB - PURPOSE: To collect data on primary treatment decision and follow-up in patients with diagnosed, histologically confirmed localized (T1a-T2c/N0/M0) prostate cancer (PCa) for up to 5 years in a prospective observational non-interventional study. METHODS: Patients were non-randomly allocated to one of the five treatment strategies: hormone therapy, active surveillance, radiation, operation, or watchful waiting. RESULTS: A total of 3169 patients were included by 259 participating sites; 2957 patients had at least one follow-up visit. 54.8 % of tumors at baseline were staged as T1c, 38 % as T2a-T2c, and 7.1 % as T1a or T1b (missing: 0.2 %). 38.9, 32.6 and 26.6 % of patients were classified as low risk, intermediate risk, and high risk according to d'Amico, respectively (missing: 1.8 %). 56.6 % of patients underwent prostatectomy as primary therapy, 16.4 % received radiation, 6.9 % HT, 15.8 and 4.3 % decided for AS or WW. Mean follow-up was 28.4 months. Progression rates were between 8.6 % (RT) and 33.1 % (AS). CONCLUSION: Whereas RP remains the main treatment option of localized PCa, active surveillance appears to become an accepted and selectively employed treatment option. Careful selection of patients is documented by the highest proportion of patients with low risk (82.5 %), PSA density <0.2 ng/ml/ml (77.5 %), T1 staging (83.6 %), Gleason score <=6 (92.5 %), <=2 positive biopsies (79.4 %), and lowest mean PSA (5.8 ng/ml) in the AS group. The relatively high progression rate in the AS group has to be considered in the context of treatment changes; 71/155 patients had a documented change of treatment and 62 of them with a follow-up period of >3 months. PMID- 26373956 TI - What do we know about treatment sequencing of abiraterone, enzalutamide, and chemotherapy in metastatic castration-resistant prostate cancer? AB - PURPOSE: To present a systematic review of the different therapeutic sequences in metastatic castration-resistant prostate cancer (mCRPC). METHODS: Evidence acquisition on therapeutic sequences in mCRPC was performed by a MEDLINE search using combination of the following key words: "prostate cancer," "metastatic," "castration resistant," "enzalutamide," "abiraterone," "treatment sequencing," "cabazitaxel," "docetaxel." A total of 17 studies were included for analysis. RESULTS: Different sequences have been reported for the treatment of mCRPC: docetaxel after abiraterone, cabazitaxel after docetaxel and abiraterone, abiraterone after cabazitaxel and docetaxel, abiraterone after docetaxel and enzalutamide, and enzalutamide after docetaxel and abiraterone. There are arguments from the preclinical observations suggesting a cross-resistance between docetaxel and abiraterone, and between abiraterone and enzalutamide in mCRPC. Despite limitations, several retrospective clinical reports support these data. CONCLUSION: No study of high level of evidence is available to support any recommendation on sequential treatment for mCRPC. There are only clues that prospective clinical studies need to confirm. PMID- 26373957 TI - Pharmacokinetic and pharmacodynamic considerations for the next generation protein therapeutics. AB - Increasingly sophisticated protein engineering efforts have been undertaken lately to generate protein therapeutics with desired properties. This has resulted in the discovery of the next generation of protein therapeutics, which include: engineered antibodies, immunoconjugates, bi/multi-specific proteins, antibody mimetic novel scaffolds, and engineered ligands/receptors. These novel protein therapeutics possess unique physicochemical properties and act via a unique mechanism-of-action, which collectively makes their pharmacokinetics (PK) and pharmacodynamics (PD) different than other established biological molecules. Consequently, in order to support the discovery and development of these next generation molecules, it becomes important to understand the determinants controlling their PK/PD. This review discusses the determinants that a PK/PD scientist should consider during the design and development of next generation protein therapeutics. In addition, the role of systems PK/PD models in enabling rational development of the next generation protein therapeutics is emphasized. PMID- 26373958 TI - Body composition of term healthy Indian newborns. AB - BACKGROUND/OBJECTIVES: Previous anthropometry-based studies have suggested that in Indian newborns fat mass is conserved at the expense of lean tissue. This study was undertaken to assess the body composition of Indian newborns and to evaluate its relation with parents' anthropometry, birth weight and early postnatal weight gain. SUBJECTS/METHODS: Body composition of healthy term singleton newborns was assessed by the deuterium dilution method in the second week of life. Anthropometry was carried out at birth and on the day of study. RESULTS: Data from 127 babies were analyzed. Birth weight was 2969+/-383 g. Body composition was assessed at a mean age of 12.7+/-3.1 days. Fat and fat-free mass were 354+/-246 and 2764+/-402 g, respectively, and fat mass percentage (FM%) was 11.3+/-7.3%. Birth weight and fat-free mass were higher among boys, but no gender difference was noted in FM%. Birth weight was positively correlated with fat as well as fat-free mass but not FM%. FM% showed positive correlation with gain in weight from birth to the day of assessment. CONCLUSIONS: This is the first study from India to report body composition in newborns using deuterium dilution. FM% was comparable to that reported for Western populations for babies of similar age. Our results suggest that the percentage of fat and fat-free mass is relatively constant over the range of birth weights included in this study, and greater weight gain during early postnatal period results in greater increase in FM%. PMID- 26373959 TI - The nutrition contribution of dietary supplements on total nutrient intake in children and adolescents. AB - BACKGROUND/OBJECTIVES: The use of dietary supplements (DSs) by children and adolescents is increasing. The aim of this study was to identify the characteristics of DS users and examine the nutritional contributions of DSs to total nutrient intakes in children and adolescents, using data obtained from a national survey. SUBJECTS/METHODS: In total, 3134 subjects aged 9-18 years who participated in the 4th Korea National Health and Nutrition Examination Survey (2007-2009) were selected; the survey included 24-h recall questions on food intake and questions on DS use over the past year. Nutrient intakes from DSs were calculated using the aid of a label-based database on such supplements, and individual total nutrient intakes were derived by combining information on the foods and DSs consumed by each subject. RESULTS: There were 895 DS users (28.5%), 85.2% of whom (n=577) had complete DS nutrient information and were therefore defined as identified-DS users. Identified-DS users were slightly younger and had a greater household income and better nutritional knowledge than did non-users. The most frequently consumed type of supplement was a 'multivitamin and minerals' complex. For total nutrient intake, identified-DS users had a significantly higher intake of most of the nutrients, except for macronutrient and sodium than non-users. In all identified-DS users, the contribution of vitamins and minerals from DSs to total nutrient intake was higher than energy and macronutrients. CONCLUSIONS: DS use by children and adolescents can improve micronutrient status, but it also increases the risk of excessive intake of certain vitamins and minerals. PMID- 26373960 TI - Am I making a difference? Measuring dietetic outcomes in clinical practice. PMID- 26373961 TI - Are edible insects more or less 'healthy' than commonly consumed meats? A comparison using two nutrient profiling models developed to combat over- and undernutrition. AB - BACKGROUND/OBJECTIVES: Insects have been the subject of recent attention as a potentially environmentally sustainable and nutritious alternative to traditional protein sources. The purpose of this paper is to test the hypothesis that insects are nutritionally preferable to meat, using two evaluative tools that are designed to combat over- and under-nutrition. SUBJECTS/METHODS: We selected 183 datalines of publicly available data on the nutrient composition of raw cuts and offal of three commonly consumed meats (beef, pork and chicken), and six commercially available insect species, for energy and 12 relevant nutrients. We applied two nutrient profiling tools to this data: The Ofcom model, which is used in the United Kingdom, and the Nutrient Value Score (NVS), which has been used in East Africa. We compared the median nutrient profile scores of different insect species and meat types using non-parametric tests and applied Bonferroni adjustments to assess for statistical significance in differences. RESULTS: Insect nutritional composition showed high diversity between species. According to the Ofcom model, no insects were significantly 'healthier' than meat products. The NVS assigned crickets, palm weevil larvae and mealworm a significantly healthier score than beef (P<0.001) and chicken (P<0.001). No insects were statistically less healthy than meat. CONCLUSIONS: Insect nutritional composition is highly diverse in comparison with commonly consumed meats. The food category 'insects' contains some foods that could potentially exacerbate diet-related public health problems related to over-nutrition, but may be effective in combating under-nutrition. PMID- 26373963 TI - Hydrothermally modified slow release corn starch: a potential new therapeutic option for treating hypoglycemia in autoimmune hypoglycemia (Hirata's disease). AB - We report the successful treatment of autoimmune hypoglycemia in an 82-year-old non-diabetic Caucasian male with hydrothermally modified slow release corn starch, a product which is used in other conditions associated with hypoglycemia, most typically glycogen storage disease type I. An 82-year-old-Caucasian male presented with recurrent spontaneous hypoglycemia as low as 30 mg/dl following in patient treatment for community acquired pneumonia. During a fasting-test, symptomatic hypoglycemia occurred. Plasma concentrations of c-peptide and insulin were considerably elevated. Autoimmune hypoglycemia was confirmed by the presence of insulin autoantibodies. While dietary restriction alone did not result in sufficient glucose control in this patient with autoimmune hypoglycemia, treatment with hydrothermally modified slow release corn starch led to stable euglycemia. This easy, well tolerated and non-invasive treatment may constitute a new therapeutic option for hypoglycemia in patients with autoimmune hypoglycemia who do not achieve sufficient control of hypoglycemia by dietary restriction alone. PMID- 26373962 TI - Iron deficiency in early pregnancy using serum ferritin and soluble transferrin receptor concentrations are associated with pregnancy and birth outcomes. AB - BACKGROUND/OBJECTIVES: There are several biomarkers for measuring iron deficiency (ID) in pregnancy, but the prevalence of ID and its association with inflammation and adverse pregnancy outcomes is inconclusive. The aim of this work was to describe the prevalence and determinants of first trimester ID and associations with pregnancy and birth outcomes. SUBJECTS/METHODS: A record-linkage cohort study of archived serum samples of women attending first trimester screening and birth and hospital data to ascertain maternal characteristics and pregnancy outcomes. Sera were analysed for iron stores (ferritin; MUg/l), lack of iron in the tissues (soluble transferrin receptor (sTfR); nmol/l) and inflammatory (C reactive protein (CRP); mg/dl) biomarkers. Total body iron (TBI) was calculated from serum ferritin (SF) and sTfR concentrations. Multivariate logistic regression analysed risk factors and pregnancy outcomes associated with ID using the definitions: SF<12 MUg/l, TfR ? 21.0 nmol/l, and TBI<0 mg/kg. RESULTS: Of the 4420 women, the prevalence of ID based on ferritin, sTfR and TBI was 19.6, 15.3 and 15.7%, respectively. Risk factors of ID varied depending on which iron parameter was used and included maternal age <25 years, multiparity, socioeconomic disadvantage, high maternal body weight and inflammation. ID, defined by SF and TBI but not TfR, was associated with reduced risk of gestational diabetes mellitus (GDM). ID defined using TBI only was associated with increased risk of large-for-gestation-age (LGA) infants. CONCLUSIONS: Nearly one in five Australian women begin pregnancy with ID. Further investigation of excess maternal weight and inflammation in the relationships between ID and GDM and LGA infants is needed. PMID- 26373965 TI - How does the Mediterranean diet decrease the risk of a variety of cancers? PMID- 26373964 TI - Dietary vitamin A intake and bone health in the elderly: the Rotterdam Study. AB - BACKGROUND/OBJECTIVES: High vitamin A intake may be associated with a decreased bone mineral density (BMD) and increased risk of fractures. Our objectives were to study whether dietary intake of vitamin A (total, retinol or beta-carotene) is associated with BMD and fracture risk and if associations are modified by body mass index (BMI) and vitamin D. SUBJECTS/METHODS: Participants were aged 55 years and older (n=5288) from the Rotterdam Study, a population-based prospective cohort. Baseline vitamin A and D intake was measured by a food frequency questionnaire. BMD was measured by dual-energy X-ray absorptiometry at four visits between baseline (1989-1993) and 2004. Serum vitamin D was assessed in a subgroup (n=3161). Fracture incidence data were derived from medical records with a mean follow-up time of 13.9 years. RESULTS: Median intake of vitamin A ranged from 684 retinol equivalents (REs)/day (quintile 1) to 2000 REs/day (quintile 5). After adjustment for confounders related to lifestyle and socioeconomic status, BMD was significantly higher in subjects in the highest quintile of total vitamin A (mean difference in BMD (95% confidence interval (CI))=11.53 (0.37-22.7) mg/cm(2)) and retinol intake (mean difference in BMD (95% CI)=12.57 (1.10-24.05) mg/cm(2)) than in the middle quintile. Additional adjustment for BMI diluted these associations. Fracture risk was reduced in these subjects. Significant interaction was present between intake of retinol and overweight (BMI >25 kg/m(2)) in relation to fractures (P for interaction =0.05), but not BMD. Stratified analysis showed that these favourable associations with fracture risk were only present in overweight subjects (BMI >25 kg/m(2)). No effect modification by vitamin D intake or serum levels was observed. CONCLUSIONS: Our results suggest a plausible favourable relation between high vitamin A intake from the diet and fracture risk in overweight subjects, whereas the association between vitamin A and BMD is mainly explained by BMI. PMID- 26373966 TI - Automated anthropometric phenotyping with novel Kinect-based three-dimensional imaging method: comparison with a reference laser imaging system. AB - BACKGROUND/OBJECTIVES: Anthropometry for measuring body composition, shape, surface area and volume is important for human clinical research and practice. Although training and technical skills are required for traditional tape and caliper anthropometry, a new opportunity exists for automated measurement using newly developed relatively low-cost three-dimensional (3D) imaging devices. The aim of this study was to compare results provided by a Kinect-based device to a traditional laser 3D reference system. SUBJECTS/METHODS: Measurements made by the evaluated device, a hybrid of commercially purchased hardware (KX-16; TC(2), Cary, NC, USA) with our additional added software, were compared with those derived by a high-resolution laser scanner (Vitus Smart XXL; Human Solutions North America, Cary, NC, USA). Both imaging systems were compared with additional linear (stadiometer-derived height) and volumetric (total volume, air displacement plethysmography) measurements. Subjects (n=101) were healthy children (age >=5 years) and adults varying in body mass index. RESULTS: Representative linear (4), circumferential (6), volumetric (3) and surface area (1) measurements made by the Kinect-based device showed a consistent pattern relative to the laser system: high correlations (R(2)s= 0.70-0.99, all P<0.001); 1-3% differences for large linear (for example, height, X+/-s.d., -1.4+/-0.5%), circumferential (for example, waist circumference, -2.1+/-1.8%), volume (for example, total body, -0.8+/-2.2%) and surface area (whole-body, -1.7+/-2.0%) estimates. By contrast, mean measurement differences were substantially larger for small structures (for example, forearm volume, 31.3+/-31.4%). CONCLUSIONS: Low-cost 3D Kinect-based imaging systems have the potential for providing automated accurate anthropometric and related body measurements for relatively large components; further hardware and software developments may be able to improve system small-component resolution. PMID- 26373967 TI - Effect of multi-nutrient insufficiency on markers of one carbon metabolism in young women: response to a methionine load. AB - BACKGROUND/OBJECTIVES: Multi-nutrient insufficiencies as a consequence of nutritional and economic factors are common in India and other developing countries. We have examined the impact of multi-nutrient insufficiency on markers of one carbon (1C) metabolism in the blood, and response to a methionine load in clinically healthy young women. SUBJECTS/METHODS: Young women from Pune, India (n=10) and Cleveland, USA (n=13) were studied. Blood samples were obtained in the basal state and following an oral methionine load (50 mg/kg of body weight in orange juice). Plasma concentrations of vitamin B12, folate and B6 were measured in the basal state. The effect of methionine load on the levels of methionine, total homocysteine, cysteine, glutathione and amino acids was examined. RESULTS: Indian women were significantly shorter and lighter compared with the American women and had lower plasma concentration of vitamins B12, folate and B6, essential amino acids and glutathione, but higher concentration of total homocysteine. The homocysteine response to methionine load was higher in Indian women. The plasma concentrations of glycine and serine increased in the Indian women after methionine (in juice) load. A significant negative correlation between plasma B6 and homocysteine (r= -0.70), and plasma folate and glycine and serine levels were observed in the Indian group (P<0.05) but not in the American group. CONCLUSIONS: Multi-nutrient insufficiency in the Indian women caused unique changes in markers of whole body protein and 1C metabolism. These data would be useful in developing nutrient intervention strategies. PMID- 26373968 TI - Relevance of fiber integrated gelatin-nanohydroxyapatite composite scaffold for bone tissue regeneration. AB - Porous nanohydroxyapatite (nanoHA) is a promising bone substitute, but it is brittle, which limits its utility for load bearing applications. To address this issue, herein, biodegradable electrospun microfibrous sheets of poly(L-lactic acid)-(PLLA)-polyvinyl alcohol (PVA) were incorporated into a gelatin-nanoHA matrix which was investigated for its mechanical properties, the physical integration of the fibers with the matrix, cell infiltration, osteogenic differentiation and bone regeneration. The inclusion of sacrificial fibers like PVA along with PLLA and leaching resulted in improved cellular infiltration towards the center of the scaffold. Furthermore, the treatment of PLLA fibers with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide enhanced their hydrophilicity, ensuring firm anchorage between the fibers and the gelatin-HA matrix. The incorporation of PLLA microfibers within the gelatin-nanoHA matrix reduced the brittleness of the scaffolds, the effect being proportional to the number of layers of fibrous sheets in the matrix. The proliferation and osteogenic differentiation of human adipose-derived mesenchymal stem cells was augmented on the fibrous scaffolds in comparison to those scaffolds devoid of fibers. Finally, the scaffold could promote cell infiltration, together with bone regeneration, upon implantation in a rabbit femoral cortical defect within 4 weeks. The bone regeneration potential was significantly higher when compared to commercially available HA (SurgiwearTM). Thus, this biomimetic, porous, 3D composite scaffold could be offered as a promising candidate for bone regeneration in orthopedics. PMID- 26373969 TI - The long road to recombinase-mediated plant transformation. AB - The use of site-specific recombinases to manipulate eukaryotic genomes began nearly three decades ago. Although seemingly parallel efforts were being made in animal and plant systems, the motivation for its development in plants was unique to, at least at the time, crop bioengineering issues. The impetus behind site specific deletion in plants was to remove antibiotic resistance genes used during transformation but unnecessary in commercial products. Site-specific integration in plants was more than academic curiosity of position effects on gene expression, but a necessary step towards developing the serial stacking of DNA to the same chromosome locus - to insure that bioengineered crops can be improved over time through transgene additions without inflating the number of segregating loci. This article is not a review of the literature on site-specific recombination, but a first person account of the series of events leading to the development of a gene stacking transformation system in plants. PMID- 26373971 TI - Growth in bone and body size among Asian and white girls in the Female Adolescent Maturation (FAM) study. AB - RATIONALE: This study intends to identify differences in growth of Asian and White girls. MAIN RESULT: Asian girls gained bone at similar rates to White girls. Physical activity was important to bone growth. Ethnic differences remained after adjusting for physical activity, demographics, and diet. SIGNIFICANCE: Physical activity can improve bone gain. PURPOSE: The purpose of this study is to examine differences in body size and bone growth of Asian, White, and Asian-White Mixed girls. METHODS: Three prospective examinations of 99 Asian, 73 White, and 63 Mixed Asian and White girls, with a mean age of 11.0 years at enrollment were performed. Calcaneal bone mass, skeletal breadths, and body fat were measured. Physical activity, diet, and birth size were reported. The analyses examined the extent that body dimensions and bone size changed over time by demographic, diet, physical activity, body, and bone size parameters. RESULTS: White children were the most physically active yet had lower calcaneal ultrasound values for speed of sound (SOS). Based on regression models, bone mass, and subscapular skinfold thickness were greater in Asian girls compared to White and Asian-White Mixed girls at age 10 years. Asian-White Mixed girls had greater BMI compared to Asian or White girls. Asian girls gained body size more slowly than White girls, but changes in bone parameters did not differ significantly; Asian-White Mixed girls gained abdomen, hip, and weight more slowly than White girls. Among all girls, SOS and broadband ultrasound attenuation (BUA) increased significantly by level of physical activity before 12 years, but not after. CONCLUSIONS: Asian girls had more upper body (subscapular) fat at age 10 years and gained height and hip and abdomen circumferences more slowly than Asian-White and White girls. Asian girls had greater bone SOS and BUA at age 10 years but gained bone at similar rates to White girls. Physical activity was especially important to bone growth before age 12 years. However, ethnic differences remained after adjusting for physical activity, demographic, and dietary factors. PMID- 26373972 TI - Non-linear pattern of age-specific bone mineral density and related factors in women: data from the 5th Korea National Health and Nutrition Examination Survey. AB - Age-specific bone mineral density (BMD) of Korean women showed a nonlinear pattern. According to our study, this pattern could be mainly attributed to the nonlinear effects of body composition. Interventions targeting these factors in premenopausal women could be critical for achieving peak BMD. PURPOSE: The patterns of age-specific bone mineral density (BMD) of femur and spine in women showed a non-unidirectional decrease, with ups and downs around the point of achieving peak BMD, that are not evident in men. We investigated the factors associated with these age-specific BMD in women using linear and nonlinear models. METHODS: A total of 4681 women recruited during the 5th Korean National Health and Nutrition Examination Survey 2010-2011 (KNHANES V) were included. A range of related factors were considered including body compositional, reproductive, and socio-behavioral factors. Age-specific BMD was demonstrated using a generalized additive model (GAM) with smoothing spline transformation. RESULTS: Age, lean body mass, fat mass, and age at menarche were significant predictors of BMD in premenopausal women. The GAM plot of BMD according to age revealed two peaks for total femur, femoral neck, and lumbar spine. After adjustment for body compositional factors, the peaks flattened. In the full model, the pattern for lumbar spine showed a single peak around the mid-40s. The GAM showed a generally better performance than the linear model for BMD at all three sites. Reduced models that included only lean body mass and fat mass best explained the variance of BMD in GAMs. CONCLUSIONS: The BMD of Korean women in reproductive period could be largely attributed to the nonlinear effects of age and body compositional factors. Intervention targeting these factors could be critical for maintaining peak BMD. PMID- 26373974 TI - An integrative approach to understanding the evolution and diversity of Copiapoa (Cactaceae), a threatened endemic Chilean genus from the Atacama Desert. AB - PREMISE OF THE STUDY: Species of the endemic Chilean cactus genus Copiapoa have cylindrical or (sub)globose stems that are solitary or form (large) clusters and typically yellow flowers. Many species are threatened with extinction. Despite being icons of the Atacama Desert and well loved by cactus enthusiasts, the evolution and diversity of Copiapoa has not yet been studied using a molecular approach. METHODS: Sequence data of three plastid DNA markers (rpl32-trnL, trnH psbA, ycf1) of 39 Copiapoa taxa were analyzed using maximum likelihood and Bayesian inference approaches. Species distributions were modeled based on geo referenced localities and climatic data. Evolution of character states of four characters (root morphology, stem branching, stem shape, and stem diameter) as well as ancestral areas were reconstructed using a Bayesian and maximum likelihood framework, respectively. KEY RESULTS: Clades of species are revealed. Though 32 morphologically defined species can be recognized, genetic diversity between some species and infraspecific taxa is too low to delimit their boundaries using plastid DNA markers. Recovered relationships are often supported by morphological and biogeographical patterns. The origin of Copiapoa likely lies between southern Peru and the extreme north of Chile. The Copiapo Valley limited colonization between two biogeographical areas. CONCLUSIONS: Copiapoa is here defined to include 32 species and five heterotypic subspecies. Thirty species are classified into four sections and two subsections, while two species remain unplaced. A better understanding of evolution and diversity of Copiapoa will allow allocating conservation resources to the most threatened lineages and focusing conservation action on real biodiversity. PMID- 26373975 TI - Contrasting responses to water-deficit among Encelia canescens populations distributed along an aridity gradient. AB - PREMISE OF THE STUDY: Drought is the most limiting factor for plant growth and recruitment in arid environments. For widespread species, however, plant responses to drought can vary across populations because environmental conditions can vary along the range of the species. Here, we assessed whether plants of Encelia canescens from different populations along an aridity gradient in the Atacama Desert respond differently to water-deficit conditions. METHODS: We conducted a common-garden experiment using plants grown from seeds from three populations distributed along an aridity gradient to test for differences in relative growth rate (RGR), biomass, root to shoot ratios, and photosynthesis between watered and water-deficit plants. Additionally, we examined the relationship between root to shoot ratios with RGR and total plant biomass along the gradient. KEY RESULTS: Water deficit affected root to shoot ratios, biomass, and RGR, but not photosynthesis. Populations varied in RGR and biomass; plants from the most arid population had higher RGRs, but lower biomass than those from the least arid population. In watered conditions, root to shoot ratios did not vary with RGR or biomass. Conversely, with the water deficit, root to shoot ratios were negatively and positively related to biomass and RGR, respectively. CONCLUSIONS: Response to water deficit differed among E. canescens populations; plants from the lowest rainfall environment adjusted root to shoot ratios, which may have allowed for equal biomass production across treatments. In contrast, plants from the wettest population did not adjust root to shoot ratios, but were reduced in biomass. These morphological and physiological changes to water availability showed that populations can use different strategies to cope with water deficit. PMID- 26373976 TI - Phylogeny and photosynthesis of the grass tribe Paniceae. AB - PREMISE OF THE STUDY: The grass tribe Paniceae includes important food, forage, and bioenergy crops such as switchgrass, napiergrass, various millet species, and economically important weeds. Paniceae are also valuable for answering scientific and evolutionary questions about C4 photosynthetic evolution, drought tolerance, and spikelet variation. However, the phylogeny of the tribe remains incompletely resolved. METHODS: Forty-five taxa were selected from across the tribe Paniceae and outgroups for genome survey sequencing (GSS). These data were used to build a phylogenetic tree of the Paniceae based on 102 markers (78 chloroplast, 22 mitochondrial, 2 nrDNA). Ancestral state reconstruction analyses were also performed within the Paniceae using both the traditional and two subtype classification systems to test hypotheses of C4 subtype evolution. KEY RESULTS: The phylogenetic tree resolves many areas of the Paniceae with high support and provides insight into the origin and number of C4 evolution events within the tribe. The recovered phylogeny and ancestral state reconstructions support between four and seven independent origins of C4 photosynthesis within the tribe and indicate which species are potentially the closest C3 sister taxa of each of these events. CONCLUSIONS: Although the sequence of evolutionary events that produced multiple C4 subtypes within the Paniceae remains undetermined, the results presented here are consistent with only a subset of currently proposed models. The species used in this study constitute a panel of C3 and C4 grasses that are suitable for further studies on C4 photosynthesis, bioenergy, food and forage crops, and various developmental features of the Paniceae. PMID- 26373977 TI - Bud-bank and tiller dynamics of co-occurring C3 caespitose grasses in mixed-grass prairie. AB - PREMISE OF THE STUDY: Tiller recruitment from the belowground bud bank of caespitose grasses influences their ability to monopolize local resources and, hence, their genet fitness. Differences in bud production and outgrowth among tiller types within a genet and among species may explain co-occurrence of caespitose grasses. This study aimed to characterize genet bud-bank and tiller production and dynamics in two co-occurring species and compare their vegetative reproductive strategies. METHODS: Bud-bank and tiller dynamics of Hesperostipa comata and Nassella viridula, dominant C3 caespitose grasses in the northern mixed-grass prairie of North America, were assessed throughout an annual cycle. KEY RESULTS: The two species showed similar strategies, maintaining polycyclic tillers and thus creating mixed-age genet bud banks comprising multiple bud cohorts produced in different years. Vegetative tillers produced the majority of buds, whereas flowering tillers contributed little to the bud bank. Buds lived for at least 2 yr and were maintained in multiple developmental stages throughout the year. Because bud longevity rarely exceeded tiller longevity, tiller longevity drove turnover within the bud bank. Tiller population dynamics, more than bud production per tiller, determined the differential contribution of tiller types to the bud bank. Nassella viridula had higher bud production per tiller, a consistent annual tiller recruitment density, and greater longevity of buds on senesced and flowering tillers than H. comata. CONCLUSIONS: Co-occurring C3 caespitose grasses had similar bud-bank and tiller dynamics contributing to genet persistence but differed in bud characteristics that could affect genet longevity and species coexistence. PMID- 26373978 TI - Roles of mucilage in Emilia fosbergii, a myxocarpic Asteraceae: Efficient seed imbibition and diaspore adhesion. AB - PREMISE OF THE STUDY: Several angiosperm families have myxodiaspory, such as the Asteraceae in which cypselae are frequently wind-dispersed. The roles of mucilage in cypselae remain misunderstood, and the route of water uptake from substrate to embryo remains unknown. In this work, we analyze the fruits of Emilia fosbergii aiming to clarify how the water is absorbed and how the structure of the pericarp can be related to the processes of diaspore adhesion and seed imbibition. METHODS: The anatomy and ultrastructure of the cypselae of Emilia fosbergii were analyzed with histochemical tests and light, scanning and transmission electron microscopy. We assessed the roles of mucilage in seed imbibition using apoplasmic tracing with Lucifer yellow and epifluorescence microscopy and in adhesion with a sand assay. KEY RESULTS: We describe structural and ultrastructural aspects of the exocarpic cells, especially the mucilaginous twin hairs. Lucifer yellow was absorbed only by the twin hairs, the cells where water primarily enters the seed during seed imbibition. In the sand assay, the mucilage was adhesive. CONCLUSIONS: The twin hairs on the surface of the cypselae can play a dual role in the establishment of new plants of this species. First, these trichomes constitute the main passage for water intake, which is essential for seed imbibition and germination, and after imbibition, they release mucilage that can adhere the diaspore. Therefore, the presence of myxocarpy in Asteraceae could be important in anemochoric species to avoid secondary dispersal. PMID- 26373979 TI - Sensitivity of three tree ferns during their first phase of life to the variation of solar radiation and water availability in a Mexican cloud forest. AB - PREMISE OF THE STUDY: Regeneration niche differentiation promotes species coexistence and diversity; however, the ecological implications for the initial life phases of the majority of pteridophytes are unknown. We analyzed the sensitivity of gametophytes and juvenile sporophytes of the tree ferns Alsophila firma, Cyathea divergens, and Lophosoria quadripinnata to variation in light and water availability. METHODS: We evaluated gametophyte desiccation tolerance using saturated salt solutions and gametophyte solar radiation tolerance by direct exposure. We also transplanted juvenile sporophytes in environments with 7% and 23% canopy openness and two watering levels. KEY RESULTS: The response of photosynthetic efficiency and water content suggest that the gametophytes of the three species require high relative humidity, tolerate direct solar radiation for up to 30 min and that the response is not species-dependent. Sporophyte size and gas exchange were greater in the more open site, but decreased watering had a lesser effect on these variables in the more closed site. Relative growth rate correlated with the net assimilation rate and leaf weight ratio. Juvenile sporophytes of A. firma were more shade tolerant, while those of C. divergens and L. quadripinnata acclimatized to both environments. CONCLUSIONS: Specialization to humid habitats in the tree fern gametophyte restricts the species to humid forests, while differences in the plasticity of the sporophyte facilitate coexistence of the species. PMID- 26373980 TI - Delta-slope of alpha-fetoprotein improves the ability to select liver transplant patients with hepatocellular cancer. AB - OBJECTIVE: The aim of the present study was to investigate the role of different alpha-foetoprotein (AFP) determinations in order to propose a new model aimed at predicting intention-to-treat (ITT) death and post- liver transplantation (LT) recurrence in a cohort of patients with hepatocellular cancer (HCC) enlisted for LT. BACKGROUND: Recent studies have increasingly focused on the role of AFP as a useful tool for patient selection in the setting of LT for HCC. However, no definitive AFP model has been definitively validated. METHODS: A retrospective analysis was performed on 124 consecutive patients enlisted for LT in a UCL Brussels LT centre during the period January 2004 to March 2012. The median follow-up was 3.3 years (ranges: 1.7-6.3). RESULTS: The area under the receiver operating characteristic (AUROC) analysis showed the ability of the AFP delta slope as a useful prognosticator of tumour-related drop-out and post-LT recurrence. In multivariate analyses, the delta-slope was an independent predictor of ITT death [hazard ratio (HR) = 1.014, P < 0.017] and post-LT tumour recurrence (HR = 1.020, P = 0.027). The 5-year ITT survival and disease-free survival rates were 66.0% versus 36.7% and 92.3% versus 53.8%, for patients meeting and exceeding the delta-slope cut-off value of 15 ng/ml/month, respectively. CONCLUSIONS: Integration of the AFP delta-slope with conventional criteria may further improve patient selection and post-LT outcomes; prospective studies are needed to validate the present proposed model. PMID- 26373981 TI - Nurses' experiences of hospitalised patients' sleep in Sweden: a qualitative study. AB - AIMS AND OBJECTIVES: The aim was to describe nurses' experiences of patients' sleep at an emergency hospital and their perceptions of sleep-promoting interventions. BACKGROUND: Promotion of patients' sleep during hospital care is an important intervention for the nursing profession. To promote sleep and to initiate sleep-promoting interventions, nurses need basic knowledge about sleep and its physiology. Therefore, it is of importance to explore and expand knowledge about how nurses experience patients' sleep and how they perceive working with it while providing care. DESIGN: A qualitative descriptive design was used. METHODS: Data were collected from four focus groups and seven individual interviews. A total of twenty-two registered nurses participated. Data were analysed using a qualitative content analysis. RESULTS: Nurses expressed a desire and an ambition to work in ways that promote patients' sleep during hospitalisation. Nurses reported that health care services and emergency hospitals were not organised according to patients' perspective and needs. Furthermore, they did not have opportunities to work effectively to promote sleep according to the patients' wishes. Several nurses stated that they did not have sufficient knowledge about sleep and that they did the best they could under prevailing circumstances. Nurses emphasised the importance of sleep for patients and that it was an area that should be given far greater priority. CONCLUSIONS: The results indicate that nurses currently have insufficient knowledge about sleep and sleep-promoting interventions. These aspects of nursing is based on personal experience and common sense rather than being evidence based. Furthermore, sleep as a nursing topic needs to be developed and given more focus in order for nurses to be able to deliver high quality care at emergency hospitals. RELEVANCE TO CLINICAL PRACTICE: Nurses require more knowledge and education to gain deeper understanding of sleep and to deliver evidence-based, high quality care. PMID- 26373982 TI - Association between prolonged breastfeeding and bone mineral density and osteoporosis in postmenopausal women: KNHANES 2010-2011. AB - This study showed that a negative correlation between duration of breastfeeding and bone mineral density (BMD) in the lumbar spine and prolonged breastfeeding is an independent risk for osteoporosis in postmenopausal women. The present study suggests that postmenopausal women with a history of prolonged breastfeeding require more careful screening for osteoporosis. INTRODUCTION: Several studies suggest that breastfeeding and childbirth lead to maternal calcium loss and a decline in BMD. While the association between breastfeeding and BMD immediately after weaning is well-established, the effects of breastfeeding on postmenopausal women have been controversial. The aim of this study was to examine the effects of breastfeeding on bone mineral density (BMD) and the prevalence of osteoporosis in postmenopausal women. METHODS: The present study was a cross-sectional survey based on the Korea National Health and Nutrition Examination Survey (KNHANES) 2010 and 2011 data. The association between breastfeeding and BMD and osteoporosis was examined in 1222 postmenopausal women. RESULTS: The duration of breastfeeding and BMD in the lumbar spine showed a negative correlation. The association between duration of breastfeeding and BMD remained significant after adjustment for reproductive factors and other confounding factors (P = 0.008). However, the number of deliveries and age at the time of delivery did not correlate with BMD at any site after adjustment. Moreover, the prevalence of osteoporosis in postmenopausal women with a history of prolonged breastfeeding was significantly higher than that in women with a short history of breastfeeding (>=37 months, OR = 3.292; 95 % CI 1.485-7.299). The prevalence of lumbar spine fracture showed a significant increasing trend with the increase in the duration of breastfeeding. CONCLUSION: Prolonged breastfeeding was significantly associated with low BMD in the lumbar spine and higher prevalence of osteoporosis. However, the number of deliveries or age at the time of childbirth did not influence BMD. PMID- 26373983 TI - Age- and sex-specific association of circulating osteocalcin with dynamic measures of glucose homeostasis. AB - SUMMARY: Our study showed that serum osteocalcin levels are closely related to glucose metabolism in men of all ages and younger women. This association disappeared in postmenopausal women in which increases bone turnover rates. The association between serum osteocalcin levels and glucose homeostasis should be interpreted according to age and sex. INTRODUCTION: Osteocalcin, a marker of bone formation, appears to be associated with glucose homeostasis. We investigated the age- and sex-specific association of serum osteocalcin level with variables related to glucose metabolism. METHODS: This study was based on cross-sectional analysis from 719 participants aged 20-85 years after excluding patients taking antidiabetic or antiosteoporotic drugs. The subjects were divided into four groups according to age and sex as follows: men <50 years (n = 131), men >=50 years (n = 191), women <50 years (n = 108), and women >=50 years (n = 279). Anthropometric and biochemical variables including insulin resistance (HOMA-IR) and beta cell function (HOMA-beta) from a 75-g oral glucose tolerance test, and serum 25-OH-vitamin D and parathyroid hormone levels were measured. RESULTS: The serum osteocalcin level was significantly higher in women aged >=50 years compared with women <50 years (20.4 +/- 7.8 vs. 17.9 +/- 6.8 ng/ml, p < 0.001), but there was no difference between men aged >=50 years and men <50 years (16.4 +/- 5.9 vs. 16.8 +/- 6.0 ng/ml, p = 0.905). The participants diagnosed with diabetes had lower serum osteocalcin levels than normal or prediabetic participants. Multivariable regression analyses including HOMA-IR and HOMA-beta indicated that serum osteocalcin levels had a negative and independent association with HbA1c levels in men and women aged <50 years, but not in women >=50 years. CONCLUSIONS: Low osteocalcin levels are associated with impaired glucose metabolism in men and premenopausal women. The osteocalcin levels may be determined by factors related to bone metabolism in postmenopausal women. Our data suggest that the serum levels of osteocalcin associated with glucose homeostasis should be interpreted according to age and sex. PMID- 26373986 TI - Effects of monovalent cation doping on the structure, microstructure, lattice distortion and magnetic behavior of single crystalline NdMnO3 compounds. AB - Pure and 15 mol% Na, K-doped NdMnO3 compounds with perovskite structures are prepared by sol-gel method. Tiny single crystals are formed after sintering the compounds at 1000 degrees C. The effect of Na and K doping as well as the effect of sintering temperature on the formation and microstructure of NdMnO3 are studied in detail by the Rietveld refinement technique using X-ray powder diffraction data. Single phase formation and single crystalline growth are also confirmed by high resolution transmission electron microscopy (HRTEM). Bond angles and bond lengths are calculated and shown by 3D diagrams. Monovalent doping induces noticeable changes in the microstructure and yields better structural stability in these compounds. Doping results in the change of Mn-O, Nd O and Mn-O-Mn bond lengths which in turn reduces the lattice and octahedral distortion in the system along with an increase in the tolerance factor. The magnetic properties of these compounds are also modified as a result of doping. The temperature dependent magnetization results show that the Neel temperature of antiferromagnetic NdMnO3 compound is 67.2 K and the Curie temperatures of ferromagnetic Nd0.85Na0.15MnO3 and Nd0.85K0.15MnO3 compounds are 99.1 K and 98.6 K respectively. Both 15% Na and K doping results in a similar TC in doped NdMnO3 compounds. PMID- 26373985 TI - Effects of fibroblast transplantation into the internal pallidum on levodopa induced dyskinesias in parkinsonian non-human primates. AB - Recent studies have shown that fibroblast transplantation can modify the activity of basal ganglia networks in models of Parkinson's disease. To determine its effects on parkinsonian motor symptoms, we performed autologous dermal fibroblast transplantation into the internal pallidum (GPi) in two parkinsonian rhesus monkeys with stable levodopa-induced dyskinesias (LIDs). Levodopa responses were assessed every week after transplantation for three months. A reduction of between 58% and 64% in total LIDs on the contralateral side was observed in both animals. No clear LID changes were observed on the ipsilateral side. These effects lasted the entire 3-month period in one monkey, but declined after 6-8 weeks in the other. The antiparkinsonian effects of levodopa did not diminish. The results of this pilot study indicate that fibroblast transplantation into the GPi may have beneficial effects on LIDs and warrant further investigation for potential therapeutic use. PMID- 26373987 TI - Croceitalea litorea sp. nov., isolated from seashore sand. AB - Strain CBA3205T is a Gram-stain-negative, non-motile and rod-shaped bacterium that was isolated from the seashore sand of Jeju Island in South Korea. Based on the phylogenetic analysis, the most closed related species was Croceitalea eckloniae DOKDO 025T, with 94.8 % sequence similarity for the 16S rRNA gene. Strain CBA3205T was observed to grow optimally at 25-30 degrees C and at pH 8.5 in the presence of 2-3 % (w/v) NaCl. The major fatty acids of strain CBA3205T were iso-C15 : 0, iso-C15 : 1 G, and iso-C17 : 0 3-OH. The major respiratory quinone was MK-6 and the major polar lipids were two unidentified amino-group containing phospholipids and an unidentified polar lipid. The G+C content of the genomic DNA of strain CBA3205T was 62.5 mol%. Based on the phenotypic, genotypic and phylogenetic analyses, strain CBA3205T was considered to be a novel species belonging to the genus Croceitalea within the family Flavobacteriaceae, for which the name Croceitalea litorea sp. nov. is proposed. The type strain is CBA3205T ( = KACC 17669T = JCM 19531T). PMID- 26373988 TI - Exploring the influential factors in incident clearance time: Disentangling causation from self-selection bias. AB - Understanding the relationships between influential factors and incident clearance time is crucial to make effective countermeasures for incident management agencies. Although there have been a certain number of achievements on incident clearance time modeling, limited effort is made to investigate the relative role of incident response time and its self-selection in influencing the clearance time. To fill this gap, this study uses the endogenous switching model to explore the influential factors in incident clearance time, and aims to disentangle causation from self-selection bias caused by response process. Under the joint two-stage model framework, the binary probit model and switching regression model are formulated for both incident response time and clearance time, respectively. Based on the freeway incident data collected in Washington State, full information maximum likelihood (FIML) method is utilized to estimate the endogenous switching model parameters. Significant factors affecting incident response time and clearance time can be identified, including incident, temporal, geographical, environmental, traffic and operational attributes. The estimate results reveal the influential effects of incident, temporal, geographical, environmental, traffic and operational factors on incident response time and clearance time. In addition, the causality of incident response time itself and its self-selection correction on incident clearance time are found to be indispensable. These findings suggest that the causal effect of response time on incident clearance time will be overestimated if the self-selection bias is not considered. PMID- 26373990 TI - Communication: Rate coefficients of the H + CH4 -> H2 + CH3 reaction from ring polymer molecular dynamics on a highly accurate potential energy surface. AB - The ring polymer molecular dynamics (RPMD) calculations are performed to calculate rate constants for the title reaction on the recently constructed potential energy surface based on permutation invariant polynomial (PIP) neural network (NN) fitting [J. Li et al., J. Chem. Phys. 142, 204302 (2015)]. By inspecting convergence, 16 beads are used in computing free-energy barriers at 300 K <= T <= 1000 K, while different numbers of beads are used for transmission coefficients. The present RPMD rates are in excellent agreement with quantum rates computed on the same potential energy surface, as well as with the experimental measurements, demonstrating further that the RPMD is capable of producing accurate rates for polyatomic chemical reactions even at rather low temperatures. PMID- 26373989 TI - Communication: Coherences observed in vivo in photosynthetic bacteria using two dimensional electronic spectroscopy. AB - Energy transfer through large disordered antenna networks in photosynthetic organisms can occur with a quantum efficiency of nearly 100%. This energy transfer is facilitated by the electronic structure of the photosynthetic antennae as well as interactions between electronic states and the surrounding environment. Coherences in time-domain spectroscopy provide a fine probe of how a system interacts with its surroundings. In two-dimensional electronic spectroscopy, coherences can appear on both the ground and excited state surfaces revealing detailed information regarding electronic structure, system-bath coupling, energy transfer, and energetic coupling in complex chemical systems. Numerous studies have revealed coherences in isolated photosynthetic pigment protein complexes, but these coherences have not been observed in vivo due to the small amplitude of these signals and the intense scatter from whole cells. Here, we present data acquired using ultrafast video-acquisition gradient-assisted photon echo spectroscopy to observe quantum beating signals from coherences in vivo. Experiments were conducted on isolated light harvesting complex II (LH2) from Rhodobacter sphaeroides, whole cells of R. sphaeroides, and whole cells of R. sphaeroides grown in 30% deuterated media. A vibronic coherence was observed following laser excitation at ambient temperature between the B850 and the B850(*) states of LH2 in each of the 3 samples with a lifetime of ~40-60 fs. PMID- 26373991 TI - Communication: Evidence for dipole-bound excited states in gas-phase I(-) ? MI (M = Na, K, Cs) anionic salt microclusters. AB - We report the first UV laser photodissociation spectra of gas-phase I(-) ? MI (M = Na, K, Cs) alkali halide anionic microclusters. The photodepletion spectra of these clusters display strong absorption bands just below the calculated vertical detachment energies, indicative of the presence of dipole-bound excited states. Photoexcitation at the peak of the transition to the dipole-bound excited state results in production of a primary [MI](-) photofragment along with a less intense I(-) ion. The photofragmentation mechanism of the excited state cluster is discussed in the context of an initial dipole-bound excited state that subsequently relaxes via a vibrational Feschbach resonance. The experiments described have been performed in an electrospray source laser-interfaced quadrupole ion-trap instrument and demonstrated for the first time that dipole bound excited states can be identified in the relatively high-collision environment of a quadrupole ion-trap, in particular for systems with large dipole moments associated with the presence of charge separation. This indicates considerable potential for future experiments that identify dipole-bound excited states as a "low-resolution" structural probe of biomolecules and molecular charge separation using the instrumentation employed in this work. PMID- 26373992 TI - Communication: The H2@C60 inelastic neutron scattering selection rule: Expanded and explained. AB - Recently [M. Xu et al., J. Chem. Phys. 139, 064309 (2013)], an unexpected selection rule was discovered for the title system, contradicting the previously held belief that inelastic neutron scattering (INS) is not subject to any selection rules. Moreover, the newly predicted forbidden transitions, which emerge only in the context of coupled H2 translation-rotation (TR) dynamics, have been confirmed experimentally. However, a simple physical understanding, e.g., based on group theory, has been heretofore lacking. This is provided in the present paper, in which we (1) derive the correct symmetry group for the H2@C60 TR Hamiltonian and eigenstates; (2) complete the INS selection rule, and show that the set of forbidden transitions is actually much larger than previously believed; and (3) evaluate previous theoretical and experimental results, in light of the new findings. PMID- 26373993 TI - Preface: Special Topic Section on Advanced Electronic Structure Methods for Solids and Surfaces. AB - This Special Topic section on Advanced Electronic Structure Methods for Solids and Surfaces contains a collection of research papers that showcase recent advances in the high accuracy prediction of materials and surface properties. It provides a timely snapshot of a growing field that is of broad importance to chemistry, physics, and materials science. PMID- 26373994 TI - Linear scaling density matrix real time TDDFT: Propagator unitarity and matrix truncation. AB - Real time, density matrix based, time dependent density functional theory (TDDFT) proceeds through the propagation of the density matrix, as opposed to the Kohn Sham orbitals. It is possible to reduce the computational workload by imposing spatial cutoff radii on sparse matrices, and the propagation of the density matrix in this manner provides direct access to the optical response of very large systems, which would be otherwise impractical to obtain using the standard formulations of TDDFT. Following a brief summary of our implementation, along with several benchmark tests illustrating the validity of the method, we present an exploration of the factors affecting the accuracy of the approach. In particular, we investigate the effect of basis set size and matrix truncation, the key approximation used in achieving linear scaling, on the propagator unitarity and optical spectra. Finally, we illustrate that, with an appropriate density matrix truncation range applied, the computational load scales linearly with the system size and discuss the limitations of the approach. PMID- 26373995 TI - Adiabatic-connection fluctuation-dissipation DFT for the structural properties of solids-The renormalized ALDA and electron gas kernels. AB - We present calculations of the correlation energies of crystalline solids and isolated systems within the adiabatic-connection fluctuation-dissipation formulation of density-functional theory. We perform a quantitative comparison of a set of model exchange-correlation kernels originally derived for the homogeneous electron gas (HEG), including the recently introduced renormalized adiabatic local-density approximation (rALDA) and also kernels which (a) satisfy known exact limits of the HEG, (b) carry a frequency dependence, or (c) display a 1/k(2) divergence for small wavevectors. After generalizing the kernels to inhomogeneous systems through a reciprocal-space averaging procedure, we calculate the lattice constants and bulk moduli of a test set of 10 solids consisting of tetrahedrally bonded semiconductors (C, Si, SiC), ionic compounds (MgO, LiCl, LiF), and metals (Al, Na, Cu, Pd). We also consider the atomization energy of the H2 molecule. We compare the results calculated with different kernels to those obtained from the random-phase approximation (RPA) and to experimental measurements. We demonstrate that the model kernels correct the RPA's tendency to overestimate the magnitude of the correlation energy whilst maintaining a high-accuracy description of structural properties. PMID- 26373996 TI - Forces and stress in second order Moller-Plesset perturbation theory for condensed phase systems within the resolution-of-identity Gaussian and plane waves approach. AB - The forces acting on the atoms as well as the stress tensor are crucial ingredients for calculating the structural and dynamical properties of systems in the condensed phase. Here, these derivatives of the total energy are evaluated for the second-order Moller-Plesset perturbation energy (MP2) in the framework of the resolution of identity Gaussian and plane waves method, in a way that is fully consistent with how the total energy is computed. This consistency is non trivial, given the different ways employed to compute Coulomb, exchange, and canonical four center integrals, and allows, for example, for energy conserving dynamics in various ensembles. Based on this formalism, a massively parallel algorithm has been developed for finite and extended system. The designed parallel algorithm displays, with respect to the system size, cubic, quartic, and quintic requirements, respectively, for the memory, communication, and computation. All these requirements are reduced with an increasing number of processes, and the measured performance shows excellent parallel scalability and efficiency up to thousands of nodes. Additionally, the computationally more demanding quintic scaling steps can be accelerated by employing graphics processing units (GPU's) showing, for large systems, a gain of almost a factor two compared to the standard central processing unit-only case. In this way, the evaluation of the derivatives of the RI-MP2 energy can be performed within a few minutes for systems containing hundreds of atoms and thousands of basis functions. With good time to solution, the implementation thus opens the possibility to perform molecular dynamics (MD) simulations in various ensembles (microcanonical ensemble and isobaric-isothermal ensemble) at the MP2 level of theory. Geometry optimization, full cell relaxation, and energy conserving MD simulations have been performed for a variety of molecular crystals including NH3, CO2, formic acid, and benzene. PMID- 26373997 TI - Combining density functional and incremental post-Hartree-Fock approaches for van der Waals dominated adsorbate-surface interactions: Ag2/graphene. AB - A combined density functional (DFT) and incremental post-Hartree-Fock (post-HF) approach, proven earlier to calculate He-surface potential energy surfaces [de Lara-Castells et al., J. Chem. Phys. 141, 151102 (2014)], is applied to describe the van der Waals dominated Ag2/graphene interaction. It extends the dispersionless density functional theory developed by Pernal et al. [Phys. Rev. Lett. 103, 263201 (2009)] by including periodic boundary conditions while the dispersion is parametrized via the method of increments [H. Stoll, J. Chem. Phys. 97, 8449 (1992)]. Starting with the elementary cluster unit of the target surface (benzene), continuing through the realistic cluster model (coronene), and ending with the periodic model of the extended system, modern ab initio methodologies for intermolecular interactions as well as state-of-the-art van der Waals corrected density functional-based approaches are put together both to assess the accuracy of the composite scheme and to better characterize the Ag2/graphene interaction. The present work illustrates how the combination of DFT and post-HF perspectives may be efficient to design simple and reliable ab initio-based schemes in extended systems for surface science applications. PMID- 26373998 TI - Periodic local MP2 method employing orbital specific virtuals. AB - We introduce orbital specific virtuals (OSVs) to represent the truncated pair specific virtual space in periodic local Moller-Plesset perturbation theory of second order (LMP2). The OSVs are constructed by diagonalization of the LMP2 amplitude matrices which correspond to diagonal Wannier-function (WF) pairs. Only a subset of these OSVs is adopted for the subsequent OSV-LMP2 calculation, namely, those with largest contribution to the diagonal pair correlation energy and with the accumulated value of these contributions reaching a certain accuracy. The virtual space for a general (non diagonal) pair is spanned by the union of the two OSV sets related to the individual WFs of the pair. In the periodic LMP2 method, the diagonal LMP2 amplitude matrices needed for the construction of the OSVs are calculated in the basis of projected atomic orbitals (PAOs), employing very large PAO domains. It turns out that the OSVs are excellent to describe short range correlation, yet less appropriate for long range van der Waals correlation. In order to compensate for this bias towards short range correlation, we augment the virtual space spanned by the OSVs by the most diffuse PAOs of the corresponding minimal PAO domain. The Fock and overlap matrices in OSV basis are constructed in the reciprocal space. The 4-index electron repulsion integrals are calculated by local density fitting and, for distant pairs, via multipole approximation. New procedures for determining the fit-domains and the distant-pair lists, leading to higher efficiency in the 4 index integral evaluation, have been implemented. Generally, and in contrast to our previous PAO based periodic LMP2 method, the OSV-LMP2 method does not require anymore great care in the specification of the individual domains (to get a balanced description when calculating energy differences) and is in that sense a black box procedure. Discontinuities in potential energy surfaces, which may occur for PAO-based calculations if one is not careful, virtually disappear for OSV-LMP2. Moreover, due to much increased compactness of the pair-specific virtual spaces, the OSV-LMP2 calculations are faster and require much less memory than PAO-LMP2 calculations, despite the noticeable overhead of the initial OSV construction procedure. PMID- 26373999 TI - Implementation of density functional embedding theory within the projector augmented-wave method and applications to semiconductor defect states. AB - We report a new implementation of the density functional embedding theory (DFET) in the VASP code, using the projector-augmented-wave (PAW) formalism. Newly developed algorithms allow us to efficiently perform optimized effective potential optimizations within PAW. The new algorithm generates robust and physically correct embedding potentials, as we verified using several test systems including a covalently bound molecule, a metal surface, and bulk semiconductors. We show that with the resulting embedding potential, embedded cluster models can reproduce the electronic structure of point defects in bulk semiconductors, thereby demonstrating the validity of DFET in semiconductors for the first time. Compared to our previous version, the new implementation of DFET within VASP affords use of all features of VASP (e.g., a systematic PAW library, a wide selection of functionals, a more flexible choice of U correction formalisms, and faster computational speed) with DFET. Furthermore, our results are fairly robust with respect to both plane-wave and Gaussian type orbital basis sets in the embedded cluster calculations. This suggests that the density functional embedding method is potentially an accurate and efficient way to study properties of isolated defects in semiconductors. PMID- 26374000 TI - Systematic study of finite-size effects in quantum Monte Carlo calculations of real metallic systems. AB - We present a systematic and comprehensive study of finite-size effects in diffusion quantum Monte Carlo calculations of metals. Several previously introduced schemes for correcting finite-size errors are compared for accuracy and efficiency, and practical improvements are introduced. In particular, we test a simple but efficient method of finite-size correction based on an accurate combination of twist averaging and density functional theory. Our diffusion quantum Monte Carlo results for lithium and aluminum, as examples of metallic systems, demonstrate excellent agreement between all of the approaches considered. PMID- 26374001 TI - Many-body dispersion effects in the binding of adsorbates on metal surfaces. AB - A correct description of electronic exchange and correlation effects for molecules in contact with extended (metal) surfaces is a challenging task for first-principles modeling. In this work, we demonstrate the importance of collective van der Waals dispersion effects beyond the pairwise approximation for organic-inorganic systems on the example of atoms, molecules, and nanostructures adsorbed on metals. We use the recently developed many-body dispersion (MBD) approach in the context of density-functional theory [Tkatchenko et al., Phys. Rev. Lett. 108, 236402 (2012) and Ambrosetti et al., J. Chem. Phys. 140, 18A508 (2014)] and assess its ability to correctly describe the binding of adsorbates on metal surfaces. We briefly review the MBD method and highlight its similarities to quantum-chemical approaches to electron correlation in a quasiparticle picture. In particular, we study the binding properties of xenon, 3,4,9,10 perylene-tetracarboxylic acid, and a graphene sheet adsorbed on the Ag(111) surface. Accounting for MBD effects, we are able to describe changes in the anisotropic polarizability tensor, improve the description of adsorbate vibrations, and correctly capture the adsorbate-surface interaction screening. Comparison to other methods and experiment reveals that inclusion of MBD effects improves adsorption energies and geometries, by reducing the overbinding typically found in pairwise additive dispersion-correction approaches. PMID- 26374002 TI - Fragment-based (13)C nuclear magnetic resonance chemical shift predictions in molecular crystals: An alternative to planewave methods. AB - We assess the quality of fragment-based ab initio isotropic (13)C chemical shift predictions for a collection of 25 molecular crystals with eight different density functionals. We explore the relative performance of cluster, two-body fragment, combined cluster/fragment, and the planewave gauge-including projector augmented wave (GIPAW) models relative to experiment. When electrostatic embedding is employed to capture many-body polarization effects, the simple and computationally inexpensive two-body fragment model predicts both isotropic (13)C chemical shifts and the chemical shielding tensors as well as both cluster models and the GIPAW approach. Unlike the GIPAW approach, hybrid density functionals can be used readily in a fragment model, and all four hybrid functionals tested here (PBE0, B3LYP, B3PW91, and B97-2) predict chemical shifts in noticeably better agreement with experiment than the four generalized gradient approximation (GGA) functionals considered (PBE, OPBE, BLYP, and BP86). A set of recommended linear regression parameters for mapping between calculated chemical shieldings and observed chemical shifts are provided based on these benchmark calculations. Statistical cross-validation procedures are used to demonstrate the robustness of these fits. PMID- 26374003 TI - Quantum chemical ab initio prediction of proton exchange barriers between CH4 and different H-zeolites. AB - A hybrid MP2:DFT (second-order Moller-Plesset perturbation theory-density functional theory) method that combines MP2 calculations for cluster models with DFT calculations for the full periodic structure is used to localize minima and transition structures for proton jumps at different Bronsted sites in different frameworks (chabazite, faujasite, ferrierite, and ZSM-5) and at different crystallographic positions of a given framework. The MP2 limit for the periodic structures is obtained by extrapolating the results of a series of cluster models of increasing size. A coupled-cluster (CCSD(T)) correction to MP2 energies is calculated for cluster models consisting of three tetrahedra. For the adsorption energies, this difference is small, between 0.1 and 0.9 kJ/mol, but for the intrinsic proton exchange barriers, this difference makes a significant (10.85 +/ 0.25 kJ/mol) and almost constant contribution across different systems. The total values of the adsorption energies vary between 22 and 34 kJ/mol, whereas the total proton exchange energy barriers fall in the narrow range of 152-156 kJ/mol. After adding nuclear motion contributions (harmonic approximation, 298 K), intrinsic enthalpy barriers between 134 and 141 kJ/mol and apparent energy barriers between 105 and 118 kJ/mol are predicted for the different sites examined for the different frameworks. These predictions are consistent with experimental results available for faujasite, ferrierite, and ZSM-5. PMID- 26374004 TI - Range-separated double-hybrid density-functional theory applied to periodic systems. AB - Quantum chemistry methods exploiting density-functional approximations for short range electron-electron interactions and second-order Moller-Plesset (MP2) perturbation theory for long-range electron-electron interactions have been implemented for periodic systems using Gaussian-type basis functions and the local correlation framework. The performance of these range-separated double hybrids has been benchmarked on a significant set of systems including rare-gas, molecular, ionic, and covalent crystals. The use of spin-component-scaled MP2 for the long-range part has been tested as well. The results show that the value of MU = 0.5 bohr(-1) for the range-separation parameter usually used for molecular systems is also a reasonable choice for solids. Overall, these range-separated double hybrids provide a good accuracy for binding energies using basis sets of moderate sizes such as cc-pVDZ and aug-cc-pVDZ. PMID- 26374005 TI - Energy benchmarks for methane-water systems from quantum Monte Carlo and second order Moller-Plesset calculations. AB - The quantum Monte Carlo (QMC) technique is used to generate accurate energy benchmarks for methane-water clusters containing a single methane monomer and up to 20 water monomers. The benchmarks for each type of cluster are computed for a set of geometries drawn from molecular dynamics simulations. The accuracy of QMC is expected to be comparable with that of coupled-cluster calculations, and this is confirmed by comparisons for the CH4-H2O dimer. The benchmarks are used to assess the accuracy of the second-order Moller-Plesset (MP2) approximation close to the complete basis-set limit. A recently developed embedded many-body technique is shown to give an efficient procedure for computing basis-set converged MP2 energies for the large clusters. It is found that MP2 values for the methane binding energies and the cohesive energies of the water clusters without methane are in close agreement with the QMC benchmarks, but the agreement is aided by partial cancelation between 2-body and beyond-2-body errors of MP2. The embedding approach allows MP2 to be applied without loss of accuracy to the methane hydrate crystal, and it is shown that the resulting methane binding energy and the cohesive energy of the water lattice agree almost exactly with recently reported QMC values. PMID- 26374006 TI - Temperature dependence of the electronic structure of semiconductors and insulators. AB - The renormalization of electronic eigenenergies due to electron-phonon coupling (temperature dependence and zero-point motion effect) is sizable in many materials with light atoms. This effect, often neglected in ab initio calculations, can be computed using the perturbation-based Allen-Heine-Cardona theory in the adiabatic or non-adiabatic harmonic approximation. After a short description of the recent progresses in this field and a brief overview of the theory, we focus on the issue of phonon wavevector sampling convergence, until now poorly understood. Indeed, the renormalization is obtained numerically through a slowly converging q-point integration. For non-zero Born effective charges, we show that a divergence appears in the electron-phonon matrix elements at q -> Gamma, leading to a divergence of the adiabatic renormalization at band extrema. This problem is exacerbated by the slow convergence of Born effective charges with electronic wavevector sampling, which leaves residual Born effective charges in ab initio calculations on materials that are physically devoid of such charges. Here, we propose a solution that improves this convergence. However, for materials where Born effective charges are physically non-zero, the divergence of the renormalization indicates a breakdown of the adiabatic harmonic approximation, which we assess here by switching to the non-adiabatic harmonic approximation. Also, we study the convergence behavior of the renormalization and develop reliable extrapolation schemes to obtain the converged results. Finally, the adiabatic and non-adiabatic theories, with corrections for the slow Born effective charge convergence problem (and the associated divergence) are applied to the study of five semiconductors and insulators: alpha-AlN, beta-AlN, BN, diamond, and silicon. For these five materials, we present the zero-point renormalization, temperature dependence, phonon-induced lifetime broadening, and the renormalized electronic band structure. PMID- 26374007 TI - Density-matrix based determination of low-energy model Hamiltonians from ab initio wavefunctions. AB - We propose a way of obtaining effective low energy Hubbard-like model Hamiltonians from ab initio quantum Monte Carlo calculations for molecular and extended systems. The Hamiltonian parameters are fit to best match the ab initio two-body density matrices and energies of the ground and excited states, and thus we refer to the method as ab initio density matrix based downfolding. For benzene (a finite system), we find good agreement with experimentally available energy gaps without using any experimental inputs. For graphene, a two dimensional solid (extended system) with periodic boundary conditions, we find the effective on site Hubbard U(*)/t to be 1.3 +/- 0.2, comparable to a recent estimate based on the constrained random phase approximation. For molecules, such parameterizations enable calculation of excited states that are usually not accessible within ground state approaches. For solids, the effective Hamiltonian enables large scale calculations using techniques designed for lattice models. PMID- 26374008 TI - Multireference linearized coupled cluster theory for strongly correlated systems using matrix product states. AB - We propose a multireference linearized coupled cluster theory using matrix product states (MPSs-LCC) which provides remarkably accurate ground-state energies, at a computational cost that has the same scaling as multireference configuration interaction singles and doubles, for a wide variety of electronic Hamiltonians. These range from first-row dimers at equilibrium and stretched geometries to highly multireference systems such as the chromium dimer and lattice models such as periodic two-dimensional 1-band and 3-band Hubbard models. The MPS-LCC theory shows a speed up of several orders of magnitude over the usual Density Matrix Renormalization Group (DMRG) algorithm while delivering energies in excellent agreement with converged DMRG calculations. Also, in all the benchmark calculations presented here, MPS-LCC outperformed the commonly used multi-reference quantum chemistry methods in some cases giving energies in excess of an order of magnitude more accurate. As a size-extensive method that can treat large active spaces, MPS-LCC opens up the use of multireference quantum chemical techniques in strongly correlated ab initio Hamiltonians, including two- and three-dimensional solids. PMID- 26374009 TI - Singles correlation energy contributions in solids. AB - The random phase approximation to the correlation energy often yields highly accurate results for condensed matter systems. However, ways how to improve its accuracy are being sought and here we explore the relevance of singles contributions for prototypical solid state systems. We set out with a derivation of the random phase approximation using the adiabatic connection and fluctuation dissipation theorem, but contrary to the most commonly used derivation, the density is allowed to vary along the coupling constant integral. This yields results closely paralleling standard perturbation theory. We re-derive the standard singles of Gorling-Levy perturbation theory [A. Gorling and M. Levy, Phys. Rev. A 50, 196 (1994)], highlight the analogy of our expression to the renormalized singles introduced by Ren and coworkers [Phys. Rev. Lett. 106, 153003 (2011)], and introduce a new approximation for the singles using the density matrix in the random phase approximation. We discuss the physical relevance and importance of singles alongside illustrative examples of simple weakly bonded systems, including rare gas solids (Ne, Ar, Xe), ice, adsorption of water on NaCl, and solid benzene. The effect of singles on covalently and metallically bonded systems is also discussed. PMID- 26374010 TI - A coupled cluster and Moller-Plesset perturbation theory study of the pressure induced phase transition in the LiH crystal. AB - We employ Hartree-Fock, second-order Moller-Plesset perturbation, coupled cluster singles and doubles (CCSD) as well as CCSD plus perturbative triples (CCSD(T)) theory to study the pressure induced transition from the rocksalt to the cesium chloride crystal structure in LiH. We show that the calculated transition pressure converges rapidly in this series of increasingly accurate many-electron wave function based theories. Using CCSD(T) theory, we predict a transition pressure for the structural phase transition in the LiH crystal of 340 GPa. Furthermore, we investigate the potential energy surface for this transition in the parameter space of the Buerger path. PMID- 26374011 TI - Finite-temperature coupled-cluster, many-body perturbation, and restricted and unrestricted Hartree-Fock study on one-dimensional solids: Luttinger liquids, Peierls transitions, and spin- and charge-density waves. AB - One-dimensional (1D) solids exhibit a number of striking electronic structures including charge-density wave (CDW) and spin-density wave (SDW). Also, the Peierls theorem states that at zero temperature, a 1D system predicted by simple band theory to be a metal will spontaneously dimerize and open a finite fundamental bandgap, while at higher temperatures, it will assume the equidistant geometry with zero bandgap (a Peierls transition). We computationally study these unique electronic structures and transition in polyyne and all-trans polyacetylene using finite-temperature generalizations of ab initio spin unrestricted Hartree-Fock (UHF) and spin-restricted coupled-cluster doubles (CCD) theories, extending upon previous work [He et al., J. Chem. Phys. 140, 024702 (2014)] that is based on spin-restricted Hartree-Fock (RHF) and second-order many body perturbation (MP2) theories. Unlike RHF, UHF can predict SDW as well as CDW and metallic states, and unlike MP2, CCD does not diverge even if the underlying RHF reference wave function is metallic. UHF predicts a gapped SDW state with no dimerization at low temperatures, which gradually becomes metallic as the temperature is raised. CCD, meanwhile, confirms that electron correlation lowers the Peierls transition temperature. Furthermore, we show that the results from all theories for both polymers are subject to a unified interpretation in terms of the UHF solutions to the Hubbard-Peierls model using different values of the electron-electron interaction strength, U/t, in its Hamiltonian. The CCD wave function is shown to encompass the form of the exact solution of the Tomonaga Luttinger model and is thus expected to describe accurately the electronic structure of Luttinger liquids. PMID- 26374012 TI - An improved statistical analysis for predicting the critical temperature and critical density with Gibbs ensemble Monte Carlo simulation. AB - A rigorous statistical analysis is presented for Gibbs ensemble Monte Carlo simulations. This analysis reduces the uncertainty in the critical point estimate when compared with traditional methods found in the literature. Two different improvements are recommended due to the following results. First, the traditional propagation of error approach for estimating the standard deviations used in regression improperly weighs the terms in the objective function due to the inherent interdependence of the vapor and liquid densities. For this reason, an error model is developed to predict the standard deviations. Second, and most importantly, a rigorous algorithm for nonlinear regression is compared to the traditional approach of linearizing the equations and propagating the error in the slope and the intercept. The traditional regression approach can yield nonphysical confidence intervals for the critical constants. By contrast, the rigorous algorithm restricts the confidence regions to values that are physically sensible. To demonstrate the effect of these conclusions, a case study is performed to enhance the reliability of molecular simulations to resolve the n alkane family trend for the critical temperature and critical density. PMID- 26374013 TI - On the representation of many-body interactions in water. AB - Recent work has shown that the many-body expansion of the interaction energy can be used to develop analytical representations of global potential energy surfaces (PESs) for water. In this study, the role of short- and long-range interactions at different orders is investigated by analyzing water potentials that treat the leading terms of the many-body expansion through implicit (i.e., TTM3-F and TTM4 F PESs) and explicit (i.e., WHBB and MB-pol PESs) representations. It is found that explicit short-range representations of 2-body and 3-body interactions along with a physically correct incorporation of short- and long-range contributions are necessary for an accurate representation of the water interactions from the gas to the condensed phase. Similarly, a complete many-body representation of the dipole moment surface is found to be crucial to reproducing the correct intensities of the infrared spectrum of liquid water. PMID- 26374014 TI - Efficient calculation of nuclear spin-rotation constants from auxiliary density functional theory. AB - The computation of the spin-rotation tensor within the framework of auxiliary density functional theory (ADFT) in combination with the gauge including atomic orbital (GIAO) scheme, to treat the gauge origin problem, is presented. For the spin-rotation tensor, the calculation of the magnetic shielding tensor represents the most demanding computational task. Employing the ADFT-GIAO methodology, the central processing unit time for the magnetic shielding tensor calculation can be dramatically reduced. In this work, the quality of spin-rotation constants obtained with the ADFT-GIAO methodology is compared with available experimental data as well as with other theoretical results at the Hartree-Fock and coupled cluster level of theory. It is found that the agreement between the ADFT-GIAO results and the experiment is good and very similar to the ones obtained by the coupled-cluster single-doubles-perturbative triples-GIAO methodology. With the improved computational performance achieved, the computation of the spin-rotation tensors of large systems or along Born-Oppenheimer molecular dynamics trajectories becomes feasible in reasonable times. Three models of carbon fullerenes containing hundreds of atoms and thousands of basis functions are used for benchmarking the performance. Furthermore, a theoretical study of temperature effects on the structure and spin-rotation tensor of the H(12)C-(12)CH-DF complex is presented. Here, the temperature dependency of the spin-rotation tensor of the fluorine nucleus can be used to identify experimentally the so far unknown bent isomer of this complex. To the best of our knowledge this is the first time that temperature effects on the spin-rotation tensor are investigated. PMID- 26374015 TI - A study of Kramers' turnover theory in the presence of exponential memory friction. AB - Originally, the challenge of solving Kramers' turnover theory was limited to Ohmic friction, or equivalently, motion of the escaping particle governed by a Langevin equation. Mel'nikov and Meshkov [J. Chem. Phys. 85, 1018 (1986)] (MM) presented a solution valid for Ohmic friction. The turnover theory was derived more generally and for memory friction by Pollak, Grabert, and Hanggi [J. Chem. Phys. 91, 4073 (1989)] (PGH). Mel'nikov proceeded to also provide finite barrier corrections to his theory [Phys. Rev. E 48, 3271 (1993)]. Finite barrier corrections were derived only recently within the framework of PGH theory [E. Pollak and R. Ianconescu, J. Chem. Phys. 140, 154108 (2014)]. A comprehensive comparison between MM and PGH theories including finite barrier corrections and using Ohmic friction showed that the two methods gave quantitatively similar results and were in quantitative agreement with numerical simulation data. In the present paper, we extend the study of the turnover theories to exponential memory friction. By comparing with numerical simulation, we find that PGH theory is rather accurate, even in the strong friction long memory time limit, while MM theory fails. However, inclusion of finite barrier corrections to PGH theory leads to failure in this limit. The long memory time invalidates the fundamental assumption that consecutive traversals of the well are independent of each other. Why PGH theory without finite barrier corrections remains accurate is a puzzle. PMID- 26374016 TI - Effect of ensemble generalization on the highest-occupied Kohn-Sham eigenvalue. AB - There are several approximations to the exchange-correlation functional in density-functional theory, which accurately predict total energy-related properties of many-electron systems, such as binding energies, bond lengths, and crystal structures. Other approximations are designed to describe potential related processes, such as charge transfer and photoemission. However, the development of a functional which can serve the two purposes simultaneously is a long-standing challenge. Trying to address it, we employ in the current work the ensemble generalization procedure proposed by Kraisler and Kronik [Phys. Rev. Lett. 110, 126403 (2013)]. Focusing on the prediction of the ionization potential via the highest occupied Kohn-Sham eigenvalue, we examine a variety of exchange correlation approximations: the local spin-density approximation, semi-local generalized gradient approximations, and global and local hybrid functionals. Results for a test set of 26 diatomic molecules and single atoms are presented. We find that the aforementioned ensemble generalization systematically improves the prediction of the ionization potential, for various systems and exchange correlation functionals, without compromising the accuracy of total energy related properties. We specifically examine hybrid functionals. These depend on a parameter controlling the ratio of semi-local to non-local functional components. The ionization potential obtained with ensemble-generalized functionals is found to depend only weakly on the parameter value, contrary to common experience with non-generalized hybrids, thus eliminating one aspect of the so-called "parameter dilemma" of hybrid functionals. PMID- 26374017 TI - Polynomial scaling approximations and dynamic correlation corrections to doubly occupied configuration interaction wave functions. AB - A class of polynomial scaling methods that approximate Doubly Occupied Configuration Interaction (DOCI) wave functions and improve the description of dynamic correlation is introduced. The accuracy of the resulting wave functions is analysed by comparing energies and studying the overlap between the newly developed methods and full configuration interaction wave functions, showing that a low energy does not necessarily entail a good approximation of the exact wave function. Due to the dependence of DOCI wave functions on the single-particle basis chosen, several orbital optimisation algorithms are introduced. An energy based algorithm using the simulated annealing method is used as a benchmark. As a computationally more affordable alternative, a seniority number minimising algorithm is developed and compared to the energy based one revealing that the seniority minimising orbital set performs well. Given a well-chosen orbital basis, it is shown that the newly developed DOCI based wave functions are especially suitable for the computationally efficient description of static correlation and to lesser extent dynamic correlation. PMID- 26374018 TI - Generalized quantum kinetic expansion: Time scale separation between intra cluster and inter-cluster kinetics. AB - For a general two-cluster network, a new methodology of the cluster-based generalized quantum kinetic expansion (GQKE) is developed in the matrix formalism under two initial conditions: the local cluster equilibrium and system-bath factorized states. For each initial condition, the site population evolution follows exactly a distinct closed equation, where all the four terms involved are systematically expanded over inter-cluster couplings. For the system-bath factorized initial state, the numerical investigation of the two models, a biased (2, 1)-site system and an unbiased (2, 2)-site system, verifies the reliability of the GQKE and the relevance of higher-order corrections. The time-integrated site-to-site rates and the time evolution of site population reveal the time scale separation between intra-cluster and inter-cluster kinetics. The population evolution of aggregated clusters can be quantitatively described by the approximate cluster Markovian kinetics. PMID- 26374019 TI - Anisotropic time-resolved solution X-ray scattering patterns from explicit solvent molecular dynamics. AB - Time-resolved wide-angle X-ray scattering (TR-WAXS) is an emerging experimental technique used to track chemical reactions and conformational transitions of proteins in real time. Thanks to increased time resolution of the method, anisotropic TR-WAXS patterns were recently reported, which contain more structural information than isotropic patterns. So far, however, no method has been available to compute anisotropic WAXS patterns of biomolecules, thus limiting the structural interpretation. Here, we present a method to compute anisotropic TR-WAXS patterns from molecular dynamics simulations. The calculations accurately account for scattering of the hydration layer and for thermal fluctuations. For many photo-excitable proteins, given a low intensity of the excitation laser, the anisotropic pattern is described by two independent components: (i) an isotropic component, corresponding to common isotropic WAXS experiments and (ii) an anisotropic component depending on the orientation of the excitation dipole of the solute. We present a set of relations for the calculation of these two components from experimental scattering patterns. Notably, the isotropic component is not obtained by a uniform azimuthal average on the detector. The calculations are illustrated and validated by computing anisotropic WAXS patterns of a spheroidal protein model and of photoactive yellow protein. Effects due to saturated excitation at high intensities of the excitation laser are discussed, including opportunities to extract additional structural information by modulating the laser intensity. PMID- 26374020 TI - A projection-free method for representing plane-wave DFT results in an atom centered basis. AB - Plane wave density functional theory (DFT) is a powerful tool for gaining accurate, atomic level insight into bulk and surface structures. Yet, the delocalized nature of the plane wave basis set hinders the application of many powerful post-computation analysis approaches, many of which rely on localized atom-centered basis sets. Traditionally, this gap has been bridged via projection based techniques from a plane wave to atom-centered basis. We instead propose an alternative projection-free approach utilizing direct calculation of matrix elements of the converged plane wave DFT Hamiltonian in an atom-centered basis. This projection-free approach yields a number of compelling advantages, including strict orthonormality of the resulting bands without artificial band mixing and access to the Hamiltonian matrix elements, while faithfully preserving the underlying DFT band structure. The resulting atomic orbital representation of the Kohn-Sham wavefunction and Hamiltonian provides a gateway to a wide variety of analysis approaches. We demonstrate the utility of the approach for a diverse set of chemical systems and example analysis approaches. PMID- 26374021 TI - Ion aggregation in high salt solutions. IV. Graph-theoretical analyses of ion aggregate structure and water hydrogen bonding network. AB - Ions in high salt solutions form a variety of ion aggregates, from ion pairs to clusters and networks. Their influences on water hydrogen bonding (H-bonding) network structures have long been of great interest. Recently, we have shown that the morphological structures of ion aggregates can be analyzed by using a spectral graph analysis theory, where each ion cluster or ion network is represented by a properly defined graph with edges and vertices. Here, to further examine the network properties of ion aggregates and water H-bonding networks in high salt solutions, we consider a few representative graph-theoretical descriptors: clustering coefficient, minimum path length, global efficiency, and degree distribution of ion aggregates. From the molecular dynamics trajectories, these graph theoretical properties of ion aggregates and water structures in NaCl and kosmotropic solutions are calculated and shown to be strongly dependent on the two types of ion aggregate structures, i.e., ion cluster and ion network. Ion clusters in high NaCl solutions exhibit typical behaviors of scale free network. The corresponding graph theoretical properties of ion networks in high KSCN solutions are notably different from those of NaCl ion clusters and furthermore they are very similar to those of water hydrogen-bonding network. The present graph-theoretical analysis results indicate that the high solubility limits of KSCN and other ion-network-forming salts might originate from their ability to form a large scale morphological network that can be intertwined with co-existing water H-bonding network. Furthermore, it is shown that the graph-theoretical properties of water H-bonding network structures do not strongly depend on the nature of dissolved ions nor on the morphological structures of ion aggregates, indicating that water's H-bonding interaction and network-forming capability are highly robust. We anticipate that the present graph-theoretical analysis results of high salt solutions would provide important information on the Hofmeister ion effects on water structure. PMID- 26374022 TI - Polarizability of stereoregular polymers. AB - The Genkin-Mednis approach to the longitudinal polarizability of infinite polymer chains is revisited. It is shown that the correction of a small error in the formula for the dipole oscillator strength brings that quantity to a manifestly antihermitian form and leads to greater consistency in the computation of related quantities. PMID- 26374023 TI - Sorting of chiral active particles driven by rotary obstacles. AB - Sorting of microswimmers based on their mobility properties is of utmost importance for various branches of science and engineering. In this paper, we proposed a novel sorting method, where the mixed chiral particles can be separated by applying two opposite rotary obstacles. It is found that when the angular speed of the obstacles, the angular speed of active particles, and the self-propulsion speed satisfy a certain relation, the mixed particles can be completely separated and the capture efficiency takes its maximal value. Our results may have application in capture or sorting of chiral active particles, or even measuring the chirality of active particles. PMID- 26374024 TI - Permutation-invariant distance between atomic configurations. AB - We present a permutation-invariant distance between atomic configurations, defined through a functional representation of atomic positions. This distance enables us to directly compare different atomic environments with an arbitrary number of particles, without going through a space of reduced dimensionality (i.e., fingerprints) as an intermediate step. Moreover, this distance is naturally invariant through permutations of atoms, avoiding the time consuming associated minimization required by other common criteria (like the root mean square distance). Finally, the invariance through global rotations is accounted for by a minimization procedure in the space of rotations solved by Monte Carlo simulated annealing. A formal framework is also introduced, showing that the distance we propose verifies the property of a metric on the space of atomic configurations. Two examples of applications are proposed. The first one consists in evaluating faithfulness of some fingerprints (or descriptors), i.e., their capacity to represent the structural information of a configuration. The second application concerns structural analysis, where our distance proves to be efficient in discriminating different local structures and even classifying their degree of similarity. PMID- 26374026 TI - Chiral cavity ring down polarimetry: Chirality and magnetometry measurements using signal reversals. AB - We present the theory and experimental details for chiral-cavity-ring-down polarimetry and magnetometry, based on ring cavities supporting counterpropagating laser beams. The optical-rotation symmetry is broken by the presence of both chiral and Faraday birefringence, giving rise to signal reversals which allow rapid background subtractions. We present the measurement of the specific rotation at 800 nm of vapors of alpha-pinene, 2-butanol, and alpha-phellandrene, the measurement of optical rotation of sucrose solutions in a flow cell, the measurement of the Verdet constant of fused silica, and measurements and theoretical treatment of evanescent-wave optical rotation at a prism surface. Therefore, these signal-enhancing and signal-reversing methods open the way for ultrasensitive polarimetry measurements in gases, liquids and solids, and at surfaces. PMID- 26374025 TI - Counting tagged molecules one by one: Quantitative photoactivation and bleaching of photoactivatable fluorophores. AB - Determining the number of molecules in a given assembly, such as the number of proteins in a toxic aggregate, is often critical to understanding chemistry and function. Herein, we report a variation of a limitless method for counting photoactivatable fluorescent dyes in which single dye molecules are photoswitched to a fluorescent state, counted, and then irreversibly photobleached. We use this method to count the number of CAGE 552 covalently bound to the surface of 500 nm polystyrene beads. Activation of CAGE 552 was achieved with a 405 nm laser pulse. Once activated, the dye was excited with 532 nm light, and the fluorescence emission was collected with a CCD camera. The results from the fluorescence experiments were then compared to bulk fluorescence measurements to assess the error in counting. There are other ways of counting molecules, such as photobleaching and statistical analysis of reversible switchable chromophores. The method reported here provides a lower bound to the number of chromophores, with no upper limit to the number of molecules that can be quantified. PMID- 26374027 TI - Determining the band gap and mean kinetic energy of atoms from reflection electron energy loss spectra. AB - Reflection electron energy loss spectra from some insulating materials (CaCO3, Li2CO3, and SiO2) taken at relatively high incoming electron energies (5-40 keV) are analyzed. Here, one is bulk sensitive and a well-defined onset of inelastic excitations is observed from which one can infer the value of the band gap. An estimate of the band gap was obtained by fitting the spectra with a procedure that includes the recoil shift and recoil broadening affecting these measurements. The width of the elastic peak is directly connected to the mean kinetic energy of the atom in the material (Doppler broadening). The experimentally obtained mean kinetic energies of the O, C, Li, Ca, and Si atoms are compared with the calculated ones, and good agreement is found, especially if the effect of multiple scattering is taken into account. It is demonstrated experimentally that the onset of the inelastic excitation is also affected by Doppler broadening. Aided by this understanding, we can obtain a good fit of the elastic peak and the onset of inelastic excitations. For SiO2, good agreement is obtained with the well-established value of the band gap (8.9 eV) only if it is assumed that the intensity near the edge scales as (E - Egap)(1.5). For CaCO3, the band gap obtained here (7 eV) is about 1 eV larger than the previous experimental value, whereas the value for Li2CO3 (7.5 eV) is the first experimental estimate. PMID- 26374028 TI - Analysis of heterogeneous water vapor uptake by metal iodide cluster ions via differential mobility analysis-mass spectrometry. AB - The sorption of vapor molecules onto pre-existing nanometer sized clusters is of importance in understanding particle formation and growth in gas phase environments and devising gas phase separation schemes. Here, we apply a differential mobility analyzer-mass spectrometer based approach to observe directly the sorption of vapor molecules onto iodide cluster ions of the form (MI)xM(+) (x = 1-13, M = Na, K, Rb, or Cs) in air at 300 K and with water saturation ratios in the 0.01-0.64 range. The extent of vapor sorption is quantified in measurements by the shift in collision cross section (CCS) for each ion. We find that CCS measurements are sensitive enough to detect the transient binding of several vapor molecules to clusters, which shift CCSs by only several percent. At the same time, for the highest saturation ratios examined, we observed CCS shifts of up to 45%. For x < 4, cesium, rubidium, and potassium iodide cluster ions are found to uptake water to a similar extent, while sodium iodide clusters uptake less water. For x >= 4, sodium iodide cluster ions uptake proportionally more water vapor than rubidium and potassium iodide cluster ions, while cesium iodide ions exhibit less uptake. Measured CCS shifts are compared to predictions based upon a Kelvin-Thomson-Raoult (KTR) model as well as a Langmuir adsorption model. We find that the Langmuir adsorption model can be fit well to measurements. Meanwhile, KTR predictions deviate from measurements, which suggests that the earliest stages of vapor uptake by nanometer scale species are not well described by the KTR model. PMID- 26374029 TI - Chemical accuracy from quantum Monte Carlo for the benzene dimer. AB - We report an accurate study of interactions between benzene molecules using variational quantum Monte Carlo (VMC) and diffusion quantum Monte Carlo (DMC) methods. We compare these results with density functional theory using different van der Waals functionals. In our quantum Monte Carlo (QMC) calculations, we use accurate correlated trial wave functions including three-body Jastrow factors and backflow transformations. We consider two benzene molecules in the parallel displaced geometry, and find that by highly optimizing the wave function and introducing more dynamical correlation into the wave function, we compute the weak chemical binding energy between aromatic rings accurately. We find optimal VMC and DMC binding energies of -2.3(4) and -2.7(3) kcal/mol, respectively. The best estimate of the coupled-cluster theory through perturbative triplets/complete basis set limit is -2.65(2) kcal/mol [Miliordos et al., J. Phys. Chem. A 118, 7568 (2014)]. Our results indicate that QMC methods give chemical accuracy for weakly bound van der Waals molecular interactions, comparable to results from the best quantum chemistry methods. PMID- 26374030 TI - The spin and orbital contributions to the total magnetic moments of free Fe, Co, and Ni clusters. AB - We present size dependent spin and orbital magnetic moments of cobalt (Con (+), 8 <= n <= 22), iron (Fen (+), 7 <= n <= 17), and nickel cluster (Nin (+), 7 <= n <= 17) cations as obtained by X-ray magnetic circular dichroism (XMCD) spectroscopy of isolated clusters in the gas phase. The spin and orbital magnetic moments range between the corresponding atomic and bulk values in all three cases. We compare our findings to previous XMCD data, Stern-Gerlach data, and computational results. We discuss the application of scaling laws to the size dependent evolution of the spin and orbital magnetic moments per atom in the clusters. We find a spin scaling law "per cluster diameter," ~n(-1/3), that interpolates between known atomic and bulk values. In remarkable contrast, the orbital moments do likewise only if the atomic asymptote is exempt. A concept of "primary" and "secondary" (induced) orbital moments is invoked for interpretation. PMID- 26374031 TI - Resonant two-photon ionization spectroscopy of jet-cooled OsSi. AB - The optical spectrum of diatomic OsSi has been investigated for the first time, with transitions observed in the range from 15 212 to 18 634 cm(-1) (657-536 nm). Two electronic band systems have been identified along with a number of unclassified bands. Nine bands have been investigated at rotational resolution, allowing the ground state to be identified as X(3)Sigma0(+) (-), arising from the 1sigma(2)1pi(4)2sigma(2)3sigma(2)1delta(2) configuration. The ground X(3)Sigma0(+) (-) state is characterized by re = 2.1207(27) A and DeltaG1/2" = 516.315(4) cm(-1) for the most abundant isotopologue, (192)Os(28)Si (38.63%). The A1 excited electronic state, which is thought to be primarily (3)Pi1 in character, is characterized by T0 = 15 727.7(7) cm(-1), omegae = 397.0(7) cm(-1), and re = 2.236(16) A for (192)Os(28)Si. The B1 excited electronic state is characterized by T0 = 18 468.71 cm(-1), DeltaG1/2 = 324.1 cm(-1), and re = 2.1987(20) A for (192)Os(28)Si and is thought to be primarily (1)Pi1 in character. These results are placed in context through a comparison to other transition metal carbides and silicides. PMID- 26374032 TI - Electronic transition dipole moment and radiative lifetime calculations of sodium dimer ion-pair states. AB - We report here ab initio calculated electronic transition dipole moments for the sodium dimer ion pair states of (1)Sigmag (+) symmetry. They vary strongly as a function of internuclear distance because of the effect of the Na(+) + Na(-) ion pair potential, which also causes the formation of additional wells and shoulders in the molecular potential energy curves. We also present a computational study of the transition dipole moment matrix elements and lifetimes for these ion-pair states. PMID- 26374033 TI - A complete map of the ion chemistry of the naphthalene radical cation? DFT and RRKM modeling of a complex potential energy surface. AB - The fragmentation mechanisms of the naphthalene molecular ion to [M-C4H2](+*), [M C2H2](+*), [M-H2](+*), and [M-H(*)](+) were obtained at the UB3LYP/6 311+G(3df,2p)//UB3LYP/6-31G(d) level of theory and were subsequently used to calculate the microcanonical rate constants, k(E)'s, for all the steps by the Rice-Ramsperger-Kassel-Marcus formalism. The pre-equilibrium and steady state approximations were applied on different regions of the potential energy profiles to obtain the fragmentation k(E)'s and calculate the relative abundances of the ions as a function of energy. These results reproduce acceptably well the imaging photoelectron-photoion coincidence spectra of naphthalene, in the photon-energy range 14.0-18.8 eV that was previously reported by our group. Prior to dissociation, the molecular ion rapidly equilibrates with a set of isomers that includes the Z- and E-phenylvinylacetylene (PVA) radical cations. The naphthalene ion is the predominant isomer below 10 eV internal energy, with the other isomers remaining at steady state concentrations. Later on, new steady-state intermediates are formed, such as the azulene and 1-phenyl-butatriene radical cations. The naphthalene ion does not eject an H atom directly but eliminates an H2 molecule in a two-step fragmentation. H(*) loss occurs instead from the 1 phenyl-butatriene ion. The PVA ions initiate the ejection of diacetylene (C4H2) to yield the benzene radical cation. Acetylene elimination yields the pentalene cation at low energies (where it can account for 45.9%-100.0% of the rate constant of this channel), in a three-step mechanism starting from the azulene ion. However, above 7.6 eV, the major [M-C2H2](+*) structure is the phenylacetylene cation. PMID- 26374034 TI - Post-recombination early Universe cooling by translation-internal inter conversion: The role of minor constituents. AB - Little is known of the mechanism by which H and H2, the principal constituents of the post-re-combination early Universe, cooled sufficiently to permit cluster formation, nucleosynthesis, and, eventually, the formation of structured objects. Radiative decay primarily cools the internal modes of H2, as Deltaj = - 2 jumps accompany quadrupolar emission. This, however, would be a self-limiting mechanism. In this work, a translational energy cooling mechanism based on collision-induced, translation-to-internal mode conversion, is extended, following an earlier study [A. J. McCaffery and R. J. Marsh, J. Chem. Phys. 139, 234310 (2013)] of ensembles comprising H2 in a H atom bath gas. Here, the possible influence of minor species, such as HD, on this cooling mechanism is investigated. Results suggest that the influence of HD is small but not insignificant. Conversion is very rapid and an overall translation-to-internal energy conversion efficiency of some 5% could be expected. This finding may be of use in the further development of models of this complex phase of early Universe evolution. An unexpected finding in this study was that H2 + HD ensembles are capable of very rapid translation-to-internal conversion with efficiencies of >40% and relaxation rates that appear to be relatively slow. This may have potential as an energy storage mechanism. PMID- 26374035 TI - Acetic acid dimers in a nitrogen matrix: Observation of structures containing the higher-energy conformer. AB - Acetic acid (AA) dimers are studied experimentally by infrared spectroscopy in a N2 matrix and theoretically at the MP2/6-311++G(2d,2p) level of approximation. This work is focused on the first preparation and characterization of structures containing the higher-energy (cis) conformer of AA. Nine trans-trans, fourteen trans-cis, and six cis-cis dimers are theoretically predicted. Five trans-trans and a number of trans-cis dimers are identified in the experiments, but no indication of cis-cis dimers is found. Two trans-trans dimers and the trans-cis dimers are reported for the first time. One trans-cis dimer is prepared by selective vibrational excitation of the structurally related trans-trans dimer, which converts one of the trans subunits to the cis form. Several trans-cis dimers are obtained by annealing of a matrix containing both trans and cis monomers of AA. Tunneling-induced conversion of the trans-cis dimers into trans trans forms (including two new trans-trans forms) is observed at low temperatures. PMID- 26374036 TI - Dynamics of dipole- and valence bound anions in iodide-adenine binary complexes: A time-resolved photoelectron imaging and quantum mechanical investigation. AB - Dipole bound (DB) and valence bound (VB) anions of binary iodide-adenine complexes have been studied using one-color and time-resolved photoelectron imaging at excitation energies near the vertical detachment energy. The experiments are complemented by quantum chemical calculations. One-color spectra show evidence for two adenine tautomers, the canonical, biologically relevant A9 tautomer and the A3 tautomer. In the UV-pump/IR-probe time-resolved experiments, transient adenine anions can be formed by electron transfer from the iodide. These experiments show signals from both DB and VB states of adenine anions formed on femto- and picosecond time scales, respectively. Analysis of the spectra and comparison with calculations suggest that while both the A9 and A3 tautomers contribute to the DB signal, only the DB state of the A3 tautomer undergoes a transition to the VB anion. The VB anion of A9 is higher in energy than both the DB anion and the neutral, and the VB anion is therefore not accessible through the DB state. Experimental evidence of the metastable A9 VB anion is instead observed as a shape resonance in the one-color photoelectron spectra, as a result of UV absorption by A9 and subsequent electron transfer from iodide into the empty pi-orbital. In contrast, the iodide-A3 complex constitutes an excellent example of how DB states can act as doorway state for VB anion formation when the VB state is energetically available. PMID- 26374037 TI - Intramolecular competition between n-pair and pi-pair hydrogen bonding: Microwave spectrum and internal dynamics of the pyridine-acetylene hydrogen-bonded complex. AB - a-type rotational spectra of the hydrogen-bonded complex formed from pyridine and acetylene are reported. Rotational and (14)N hyperfine constants indicate that the complex is planar with an acetylenic hydrogen directed toward the nitrogen. However, unlike the complexes of pyridine with HCl and HBr, the acetylene moiety in HCCH-NC5H5 does not lie along the symmetry axis of the nitrogen lone pair, but rather, forms an average angle of 46 degrees with the C2 axis of the pyridine. The a-type spectra of HCCH-NC5H5 and DCCD-NC5H5 are doubled, suggesting the existence of a low lying pair of tunneling states. This doubling persists in the spectra of HCCD-NC5H5, DCCH-NC5H5, indicating that the underlying motion does not involve interchange of the two hydrogens of the acetylene. Single (13)C substitution in either the ortho- or meta-position of the pyridine eliminates the doubling and gives rise to separate sets of spectra that are well predicted by a bent geometry with the (13)C on either the same side ("inner") or the opposite side ("outer") as the acetylene. High level ab initio calculations are presented which indicate a binding energy of 1.2 kcal/mol and a potential energy barrier of 44 cm(-1) in the C2v configuration. Taken together, these results reveal a complex with a bent hydrogen bond and large amplitude rocking of the acetylene moiety. It is likely that the bent equilibrium structure arises from a competition between a weak hydrogen bond to the nitrogen (an n-pair hydrogen bond) and a secondary interaction between the ortho-hydrogens of the pyridine and the pi electron density of the acetylene. PMID- 26374038 TI - Precise equilibrium structure determination of hydrazoic acid (HN3) by millimeter wave spectroscopy. AB - The millimeter-wave spectrum of hydrazoic acid (HN3) was analyzed in the frequency region of 235-450 GHz. Transitions from a total of 14 isotopologues were observed and fit using the A-reduced or S-reduced Hamiltonian. Coupled cluster calculations were performed to obtain a theoretical geometry, as well as rotation-vibration interaction corrections. These calculated vibration-rotation correction terms were applied to the experimental rotational constants to obtain mixed theoretical/experimental equilibrium rotational constants (Ae, Be, and Ce). These equilibrium rotational constants were then used to obtain an equilibrium (Re) structure using a least-squares fitting routine. The Re structural parameters are consistent with a previously published Rs structure, largely falling within the uncertainty limits of that Rs structure. The present Re geometric parameters of HN3 are determined with exceptionally high accuracy, as a consequence of the large number of isotopologues measured experimentally and the sophisticated (coupled-cluster theoretical treatment (CCSD(T))/ANO2) of the vibration-rotation interactions. The Re structure exhibits remarkable agreement with the CCSD(T)/cc-pCV5Z predicted structure, validating both the accuracy of the ab initio method and the claimed uncertainties of the theoretical/experimental structure determination. PMID- 26374039 TI - Anisotropic superfluidity of (4)He on a C36 fullerene molecule. AB - We have performed path-integral Monte Carlo calculations to study the adsorption of (4)He atoms on two different C36 isomers with the D6h and the D2d symmetries. The radial (4)He density distributions reveal layer-by-layer growth with the first layer being located at a distance of ~5.5 A from the C36 molecular center and the second layer at ~8.3 A. From the angular density profiles of (4)He, we find different quantum states as the number of (4)He adatoms N varies. For N = 20, we observe commensurate solid structures on both D6h and D2d isomers, where each of 8 hexagon and 12 pentagon centers of the fullerene surfaces is occupied by a single (4)He atom. The second-layer promotion starts beyond N = 38 on both isomers, where a compressible incommensurate structure is observed on the D6h isomer and another commensurate structure on D2d. Between N = 20 and N = 38, the (4)He monolayer on D6h shows several distinct rings of delocalized (4)He atoms along with strongly anisotropic superfluid responses at low temperatures, while isotropic but weak superfluid responses are observed in the (4)He layer on D2d. PMID- 26374041 TI - Molecular hydrogen messengers can lead to structural infidelity: A cautionary tale of protonated glycine. AB - The effects of tagging protonated glycine with either He or between 1 and 14 H2 molecules on the infrared photodissociation spectra and the ion structure were investigated. Differences in the IR spectra with either a single He atom or H2 molecule attached indicate that even a single H2 molecule can affect the frequencies of some vibrational bands of this simple ion. The protonation site is the preferred location of the tag with He and with up to two H2 molecules, but evidence for H2 attachment to the hydrogen atom of the uncharged carboxylic acid is observed for ions tagged with three or more H2 molecules. This results in a 55 cm(-1) red shift in the carboxylic acid OH stretch, and evidence for some structural isomers where the hydrogen bond between the protonated nitrogen and the carbonyl oxygen is partially broken; as a result H2 molecules attached to this site are observed. These results are supported by theory, which indicates that H2 molecules can effectively break this weak hydrogen bond with three or more H2 molecules. These results indicate that large spectral shifts as a result of H2 molecules attaching to sites remote from the charge can occur and affect stretching frequencies as a result of charge transfer, and that tagging with multiple H2 molecules can change the structure of the ion itself. PMID- 26374040 TI - Assignment of the vibrations of the S0, S1, and D0 (+) states of perhydrogenated and perdeuterated isotopologues of chlorobenzene. AB - We report vibrationally resolved spectra of the S1<-S0 transition of chlorobenzene using resonance-enhanced multiphoton ionization spectroscopy. We study chlorobenzene-h5 as well as its perdeuterated isotopologue, chlorobenzene d5. Changes in the form of the vibrational modes between the isotopologues and also between the S0 and S1 electronic states are discussed for each species. Vibrational bands are assigned utilizing quantum chemical calculations, previous experimental results, and isotopic shifts, including those between the (35)Cl and (37)Cl isotopologues. Previous work and assignments of the S1 spectra are discussed. Additionally, the vibrations in the ground state cation, D0 (+), are considered, since these have also been used by previous workers in assigning the excited neutral state spectra. PMID- 26374042 TI - Crossing the dividing surface of transition state theory. III. Once and only once. Selecting reactive trajectories. AB - The purpose of the present work is to determine initial conditions that generate reacting, recrossing-free trajectories that cross the conventional dividing surface of transition state theory (i.e., the plane in configuration space passing through a saddle point of the potential energy surface and perpendicular to the reaction coordinate) without ever returning to it. Local analytical equations of motion valid in the neighborhood of this planar surface have been derived as an expansion in Poisson brackets. We show that the mere presence of a saddle point implies that reactivity criteria can be quite simply formulated in terms of elements of this series, irrespective of the shape of the potential energy function. Some of these elements are demonstrated to be equal to a sum of squares and thus to be necessarily positive, which has a profound impact on the dynamics. The method is then applied to a three-dimensional model describing an atom-diatom interaction. A particular relation between initial conditions is shown to generate a bundle of reactive trajectories that form reactive cylinders (or conduits) in phase space. This relation considerably reduces the phase space volume of initial conditions that generate recrossing-free trajectories. Loci in phase space of reactive initial conditions are presented. Reactivity is influenced by symmetry, as shown by a comparative study of collinear and bent transition states. Finally, it is argued that the rules that have been derived to generate reactive trajectories in classical mechanics are also useful to build up a reactive wave packet. PMID- 26374043 TI - Flow of methane in shale nanopores at low and high pressure by molecular dynamics simulations. AB - Flow in shale nanopores may be vastly different from that in the conventional permeable media. In large pores and fractures, flow is governed by viscosity and pressure-driven. Convection describes the process. Pores in some shale media are in nanometer range. At this scale, continuum flow mechanism may not apply. Knudsen diffusion and hydrodynamic expressions such as the Hagen-Poiseuille equation and their modifications have been used to compute flow in nanopores. Both approaches may have drawbacks and can significantly underestimate molecular flux in nanopores. In this work, we use the dual control volume-grand canonical molecular dynamics simulations to investigate methane flow in carbon nanopores at low and high pressure conditions. Our simulations reveal that methane flow in a slit pore width of 1-4 nm can be more than one order of magnitude greater than that from Knudsen diffusion at low pressure and the Hagen-Poiseuille equation at high pressure. Knudsen diffusion and Hagen-Poiseuille equations do not account for surface adsorption and mobility of the adsorbed molecules, and inhomogeneous fluid density distributions. Mobility of molecules in the adsorbed layers significantly increases molecular flux. Molecular velocity profiles in nanopores deviate significantly from the Navier-Stokes hydrodynamic predictions. Our molecular simulation results are in agreement with the enhanced flow measurements in carbon nanotubes. PMID- 26374044 TI - Fluctuation-induced forces governed by the dielectric properties of water-A contribution to the hydrophobic interaction. AB - The hydrophobic interaction between objects immersed in water is typically attractive and adds to the well-known van der Waals interaction. The former supposedly dominates the latter on nanometric distances and could be of major importance in the assembly of biologic objects. Here, we show that the fluctuation-induced attraction between two objects immersed in a correlated dielectric medium which models water is the sum of a van der Waals term and a short-range contribution that can be identified as part of the hydrophobic interaction. In this framework, we calculate analytically the fluid correlation function and the fluctuation-induced interaction between small and extended inclusions embedded in water and we characterize the hydrophobic terms. PMID- 26374045 TI - Pressure-induced emergence of unusually high-frequency transverse excitations in a liquid alkali metal: Evidence of two types of collective excitations contributing to the transverse dynamics at high pressures. AB - Unlike phonons in crystals, the collective excitations in liquids cannot be treated as propagation of harmonic displacements of atoms around stable local energy minima. The viscoelasticity of liquids, reflected in transition from the adiabatic to elastic high-frequency speed of sound and in absence of the long wavelength transverse excitations, results in dispersions of longitudinal (L) and transverse (T) collective excitations essentially different from the typical phonon ones. Practically, nothing is known about the effect of high pressure on the dispersion of collective excitations in liquids, which causes strong changes in liquid structure. Here dispersions of L and T collective excitations in liquid Li in the range of pressures up to 186 GPa were studied by ab initio simulations. Two methodologies for dispersion calculations were used: direct estimation from the peak positions of the L/T current spectral functions and simulation-based calculations of wavenumber-dependent collective eigenmodes. It is found that at ambient pressure, the longitudinal and transverse dynamics are well separated, while at high pressures, the transverse current spectral functions, density of vibrational states, and dispersions of collective excitations yield evidence of two types of propagating modes that contribute strongly to transverse dynamics. Emergence of the unusually high-frequency transverse modes gives evidence of the breakdown of a regular viscoelastic theory of transverse dynamics, which is based on coupling of a single transverse propagating mode with shear relaxation. The explanation of the observed high-frequency shift above the viscoelastic value is given by the presence of another branch of collective excitations. With the pressure increasing, coupling between the two types of collective excitations is rationalized within a proposed extended viscoelastic model of transverse dynamics. PMID- 26374046 TI - Mechanical and thermal properties of gamma-Mg2SiO4 under high temperature and high pressure conditions such as in mantle: A first principles study. AB - gamma-Mg2SiO4 is an important mineral in mantle, and our knowledge on its mechanical and thermal properties is critical for many areas of geological sciences. In this work, the crystal structure of gamma-Mg2SiO4 under high temperature and high pressure conditions is optimized by using the GOMASC method, and the total energy, thermal expansion coefficients, and elastic constants at different temperature and pressure conditions are obtained. On the basis of phonon spectrum, group velocity, phase velocity, Gruneisen parameter, and thermal conductivity are calculated for gamma-Mg2SiO4 under high temperature and high pressure conditions. These calculated results can provide an important reference for geological research. PMID- 26374047 TI - Dynamics of glass-forming liquids. XIX. Rise and decay of field induced anisotropy in the non-linear regime. AB - For glycerol and three monohydroxy alcohols, we have measured the non-linear dielectric effects resulting from the application and removal of a high dc bias electric field. The field effects are detected by virtue of a small amplitude harmonic field, from which time resolved changes in the dielectric loss are derived. The changes in permittivity are dominated by modifications of the time constants (rather than amplitudes) which display two contributions: a heating like decrease of relaxation times that originates from the time dependent field when the bias is switched on and off and a slowing down of the dynamics resulting from the field induced reduction of configurational entropy. As observed for the electro-optical Kerr effect, the rise of the entropy change is slower than its decay, a feature that we rationalize on the basis of the quadratic dependence of the entropy change on polarization. For glycerol, the observed steady state level of the field induced shift of the glass transition temperature (+84 mK) matches the expectation based on the entropy change and its impact on dynamics via the Adam-Gibbs relation (+88 mK). For the alcohols, these non-linear effects rise and decay on the time scales of the prominent dielectric Debye process, underscoring the relation of these features to polarization anisotropy, opposed to mechanical or enthalpy relaxation which are orders of magnitude faster in these systems. A model is discussed which captures the observed magnitudes as well as time dependences in a near quantitative fashion. It is demonstrated that the high bias field modifies the response of polarization to the ac field, including a temporary change in the low field susceptibility. PMID- 26374048 TI - Secondary relaxation dynamics in rigid glass-forming molecular liquids with related structures. AB - The dielectric relaxation in three glass-forming molecular liquids, 1 methylindole (1MID), 5H-5-Methyl-6,7-dihydrocyclopentapyrazine (MDCP), and Quinaldine (QN) is studied focusing on the secondary relaxation and its relation to the structural alpha-relaxation. All three glass-formers are rigid and more or less planar molecules with related chemical structures but have dipoles of different strengths at different locations. A strong and fast secondary relaxation is detected in the dielectric spectra of 1MID, while no resolved beta relaxation is observed in MDCP and QN. If the observed secondary relaxation in 1MID is identified with the Johari-Goldstein (JG) beta-relaxation, then apparently the relation between the alpha- and beta-relaxation frequencies of 1MID is not in accord with the Coupling Model (CM). The possibility of the violation of the prediction in 1MID as due to either the formation of hydrogen bond induced clusters or the involvement of intramolecular degree of freedom is ruled out. The violation is explained by the secondary relaxation originating from the in-plane rotation of the dipole located on the plane of the rigid molecule, contributing to dielectric loss at higher frequencies and more intense than the JG beta-relaxation generated by the out-of-plane rotation. MDCP has smaller dipole moment located in the plane of the molecule; however, presence of the change of curvature of dielectric loss, epsilon"(f), at some frequency on the high-frequency flank of the alpha-relaxation reveals the JG beta-relaxation in MDCP and which is in accord with the CM prediction. QN has as large an in-plane dipole moment as 1MID, and the absence of the resolved secondary relaxation is explained by the smaller coupling parameter than the latter in the framework of the CM. PMID- 26374049 TI - Effective temperatures and the breakdown of the Stokes-Einstein relation for particle suspensions. AB - The short- and long-time breakdown of the classical Stokes-Einstein relation for colloidal suspensions at arbitrary volume fractions is explained here by examining the role that confinement and attractive interactions play in the intra and inter-cage dynamics executed by the colloidal particles. We show that the measured short-time diffusion coefficient is larger than the one predicted by the classical Stokes-Einstein relation due to a non-equilibrated energy transfer between kinetic and configuration degrees of freedom. This transfer can be incorporated in an effective kinetic temperature that is higher than the temperature of the heat bath. We propose a Generalized Stokes-Einstein relation (GSER) in which the effective temperature replaces the temperature of the heat bath. This relation then allows to obtain the diffusion coefficient once the viscosity and the effective temperature are known. On the other hand, the temporary cluster formation induced by confinement and attractive interactions of hydrodynamic nature makes the long-time diffusion coefficient to be smaller than the corresponding one obtained from the classical Stokes-Einstein relation. Then, the use of the GSER allows to obtain an effective temperature that is smaller than the temperature of the heat bath. Additionally, we provide a simple expression based on a differential effective medium theory that allows to calculate the diffusion coefficient at short and long times. Comparison of our results with experiments and simulations for suspensions of hard and porous spheres shows an excellent agreement in all cases. PMID- 26374050 TI - Wetting properties of molecularly rough surfaces. AB - We employ molecular dynamics simulations to study the wettability of nanoscale rough surfaces in systems governed by Lennard-Jones (LJ) interactions. We consider both smooth and molecularly rough planar surfaces. Solid substrates are modeled as a static collection of LJ particles arranged in a face-centered cubic lattice with the (100) surface exposed to the LJ fluid. Molecularly rough solid surfaces are prepared by removing several strips of LJ atoms from the external layers of the substrate, i.e., forming parallel nanogrooves on the surface. We vary the solid-fluid interactions to investigate strongly and weakly wettable surfaces. We determine the wetting properties by measuring the equilibrium droplet profiles that are in turn used to evaluate the contact angles. Macroscopic arguments, such as those leading to Wenzel's law, suggest that surface roughness always amplifies the wetting properties of a lyophilic surface. However, our results indicate the opposite effect from roughness for microscopically corrugated surfaces, i.e., surface roughness deteriorates the substrate wettability. Adding the roughness to a strongly wettable surface shrinks the surface area wet with the liquid, and it either increases or only marginally affects the contact angle, depending on the degree of liquid adsorption into the nanogrooves. For a weakly wettable surface, the roughness changes the surface character from lyophilic to lyophobic due to a weakening of the solid-fluid interactions by the presence of the nanogrooves and the weaker adsorption of the liquid into the nanogrooves. PMID- 26374051 TI - On sulfur core level binding energies in thiol self-assembly and alternative adsorption sites: An experimental and theoretical study. AB - Characteristic core level binding energies (CLBEs) are regularly used to infer the modes of molecular adsorption: orientation, organization, and dissociation processes. Here, we focus on a largely debated situation regarding CLBEs in the case of chalcogen atom bearing molecules. For a thiol, this concerns the case when the CLBE of a thiolate sulfur at an adsorption site can be interpreted alternatively as due to atomic adsorption of a S atom, resulting from dissociation. Results of an investigation of the characteristics of thiol self assembled monolayers (SAMs) obtained by vacuum evaporative adsorption are presented along with core level binding energy calculations. Thiol ended SAMs of 1,4-benzenedimethanethiol (BDMT) obtained by evaporation on Au display an unconventional CLBE structure at about 161.25 eV, which is close to a known CLBE of a S atom on Au. Adsorption and CLBE calculations for sulfur atoms and BDMT molecules are reported and allow delineating trends as a function of chemisorption on hollow, bridge, and atop sites and including the presence of adatoms. These calculations suggest that the 161.25 eV peak is due to an alternative adsorption site, which could be associated to an atop configuration. Therefore, this may be an alternative interpretation, different from the one involving the adsorption of atomic sulfur resulting from the dissociation process of the S-C bond. Calculated differences in S(2p) CLBEs for free BDMT molecules, SH group sulfur on top of the SAM, and disulfide are also reported to clarify possible errors in assignments. PMID- 26374052 TI - Brittle-to-ductile transition of lithiated silicon electrodes: Crazing to stable nanopore growth. AB - Using first principle calculations, we uncover the underlying mechanisms explaining the brittle-to-ductile transition of LixSi electrodes in lithium ion batteries with increasing Li content. We show that plasticity initiates at x = ~ 0.5 with the formation of a craze-like network of nanopores separated by Si-Si bonds, while subsequent failure is still brittle-like with the breaking of Si-Si bonds. Transition to ductile behavior occurs at x ? 1 due to the increased density of highly stretchable Li-Li bonds, which delays nanopore formation and stabilizes nanopore growth. Collapse of the nanopores during unloading of the LixSi alloys leads to significant strain recovery. PMID- 26374053 TI - High precision quantum-chemical treatment of adsorption: Benchmarking physisorption of molecular hydrogen on graphane. AB - A multilevel hierarchical ab initio protocol for calculating adsorption on non conducting surfaces is presented. It employs fully periodic treatment, which reaches local Moller-Plesset perturbation theory of second order (MP2) with correction for the basis set incompleteness via the local F12 technique. Post-MP2 corrections are calculated using finite clusters. That includes the coupled cluster treatment in the local and canonical frameworks (up to perturbative quadruples) and correlated core (with MP2). Using this protocol, the potential surface of hydrogen molecules adsorbed on graphane was computed. According to the calculations, hydrogen molecules are adsorbed on graphane in a perpendicular to the surface orientation with the minimum of the potential surface of around -3.6 kJ/mol located at the distance of 3.85 A between the bond center of the hydrogen molecule and the mid-plane of graphane. The adsorption sites along the path from the downward-pointing carbon to the ring center of the graphane are energetically virtually equally preferable, which can enable nearly free translations of hydrogen molecules along these paths. Consequently, the hydrogen molecules on graphane most likely form a non-commensurate monolayer. The analysis of the remaining errors reveals a very high accuracy of the computed potential surface with an error bar of a few tenths of a kJ/mol. The obtained results are a high precision benchmark for further theoretical and experimental studies of hydrogen molecules interacting with graphane. PMID- 26374054 TI - Structure and properties of water film adsorbed on mica surfaces. AB - The structure profiles and physical properties of the adsorbed water film on a mica surface under conditions with different degrees of relative humidity are investigated by a surface force apparatus. The first layer of the adsorbed water film shows ice-like properties, including a lattice constant similar with ice crystal, a high bearing capacity that can support normal pressure as high as 4 MPa, a creep behavior under the action of even a small normal load, and a character of hydrogen bond. Adjacent to the first layer of the adsorbed water film, the water molecules in the outer layer are liquid-like that can flow freely under the action of external loads. Experimental results demonstrate that the adsorbed water layer makes the mica surface change from hydrophilic to weak hydrophobic. The weak hydrophobic surface may induce the latter adsorbed water molecules to form water islands on a mica sheet. PMID- 26374055 TI - Liquid-liquid interfacial properties of a symmetrical Lennard-Jones binary mixture. AB - We determine the interfacial properties of a symmetrical binary mixture of equal sized spherical Lennard-Jones molecules, sigma11 = sigma22, with the same dispersive energy between like species, epsilon11 = epsilon22, but different dispersive energies between unlike species low enough to induce phase separation. We use the extensions of the improved version of the inhomogeneous long-range corrections of Janecek [J. Phys. Chem. B 110, 6264 (2006)], presented recently by MacDowell and Blas [J. Chem. Phys. 131, 074705 (2009)] and Martinez-Ruiz et al. [J. Chem. Phys. 141, 184701 (2014)], to deal with the interaction energy and microscopic components of the pressure tensor. We perform Monte Carlo simulations in the canonical ensemble to obtain the interfacial properties of the symmetrical mixture with different cut-off distances rc and in combination with the inhomogeneous long-range corrections. The pressure tensor is obtained using the mechanical (virial) and thermodynamic route. The liquid-liquid interfacial tension is also evaluated using three different procedures, the Irving-Kirkwood method, the difference between the macroscopic components of the pressure tensor, and the test-area methodology. This allows to check the validity of the recent extensions presented to deal with the contributions due to long-range corrections for intermolecular energy and pressure tensor in the case of binary mixtures that exhibit liquid-liquid immiscibility. In addition to the pressure tensor and the surface tension, we also obtain density profiles and coexistence densities and compositions as functions of pressure, at a given temperature. According to our results, the main effect of increasing the cut-off distance rc is to sharpen the liquid-liquid interface and to increase the width of the biphasic coexistence region. Particularly interesting is the presence of a relative minimum in the total density profiles of the symmetrical mixture. This minimum is related with a desorption of the molecules at the interface, a direct consequence of a combination of the weak dispersive interactions between unlike species of the symmetrical binary mixture, and the presence of an interfacial region separating the two immiscible liquid phases in coexistence. PMID- 26374056 TI - The energy of naturally curved elastic rods with an application to the stretching and contraction of a free helical spring as a model for DNA. AB - We give a contemporary and direct derivation of a classical, but insufficiently familiar, result in the theory of linear elasticity-a representation for the energy of a stressed elastic rod with central axis that intrinsically takes the shape of a general space curve. We show that the geometric torsion of the space curve, while playing a crucial role in the bending energy, is physically unrelated to the elastic twist. We prove that the twist energy vanishes in the lowest-energy states of a rod subject to constraints that do not restrict the twist. The stretching and contraction energies of a free helical spring are computed. There are local high-energy minima. We show the possibility of using the spring to model the chirality of DNA. We then compare our results with an available atomic level energy simulation that was performed on DNA unconstrained in the same sense as the free spring. We find some possible reflections of springlike behavior in the mechanics of DNA, but, unsurprisingly, the base pairs lend a material substance to the core of DNA that a spring does not capture. PMID- 26374057 TI - Orientational relaxation in free-standing smectic C film driven by rotating circular frame. AB - The pecularities in the c^-director reorientation in free-standing smectic C film without of defects and stretched between two circular frames, the rest outer and rotating inner, have been investigated theoretically based on the hydrodynamic theory including the c^-director motion and with accounting for backflow. Since the orientation of the c^-director is fixed at the rims of the smectic film, the shear flow induced by rotating frame winds up of the c^-director field. It is found that the higher shearing flow produces the greater twisting rotation of the c^-director around the normal to the smectic film directed in the opposite sense with respect to the direction of the angular velocity. Calculations also show that the relaxation dynamics of the c^-director field depends crucially on the curvature of the inner rotating frame. PMID- 26374058 TI - The osmotic virial formulation of the free energy of polymer mixing. AB - We derive an alternative formulation of the free energy of polymer mixing in terms of an osmotic virial expansion. Starting from a generalized free energy of mixing, and the assumption that the internal energy of mixing is analytic in the polymer composition variable, we demonstrate that the free energy of mixing can be represented as an infinite series in the osmotic virial coefficients. This osmotic virial formulation is consistent with, but more general than, a relationship derived for polymer blends with structured monomers by Dudowicz, Freed, and Douglas [J. Chem. Phys. 116, 9983 (2002)] and Douglas, Dudowicz, and Freed [J. Chem. Phys. 127, 224901 (2007)]. PMID- 26374059 TI - Extreme bendability of DNA double helix due to bending asymmetry. AB - Experimental data of the DNA cyclization (J-factor) at short length scales exceed the theoretical expectation based on the wormlike chain (WLC) model by several orders of magnitude. Here, we propose that asymmetric bending rigidity of the double helix in the groove direction can be responsible for extreme bendability of DNA at short length scales and it also facilitates DNA loop formation at these lengths. To account for the bending asymmetry, we consider the asymmetric elastic rod (AER) model which has been introduced and parametrized in an earlier study [B. Eslami-Mossallam and M. R. Ejtehadi, Phys. Rev. E 80, 011919 (2009)]. Exploiting a coarse grained representation of the DNA molecule at base pair (bp) level and using the Monte Carlo simulation method in combination with the umbrella sampling technique, we calculate the loop formation probability of DNA in the AER model. We show that the DNA molecule has a larger J-factor compared to the WLC model which is in excellent agreement with recent experimental data. PMID- 26374060 TI - Robustness, efficiency, and optimality in the Fenna-Matthews-Olson photosynthetic pigment-protein complex. AB - Pigment-protein complexes (PPCs) play a central role in facilitating excitation energy transfer (EET) from light-harvesting antenna complexes to reaction centres in photosynthetic systems; understanding molecular organisation in these biological networks is key to developing better artificial light-harvesting systems. In this article, we combine quantum-mechanical simulations and a network based picture of transport to investigate how chromophore organization and protein environment in PPCs impacts on EET efficiency and robustness. In a prototypical PPC model, the Fenna-Matthews-Olson (FMO) complex, we consider the impact on EET efficiency of both disrupting the chromophore network and changing the influence of (local and global) environmental dephasing. Surprisingly, we find a large degree of resilience to changes in both chromophore network and protein environmental dephasing, the extent of which is greater than previously observed; for example, FMO maintains EET when 50% of the constituent chromophores are removed, or when environmental dephasing fluctuations vary over two orders-of magnitude relative to the in vivo system. We also highlight the fact that the influence of local dephasing can be strongly dependent on the characteristics of the EET network and the initial excitation; for example, initial excitations resulting in rapid coherent decay are generally insensitive to the environment, whereas the incoherent population decay observed following excitation at weakly coupled chromophores demonstrates a more pronounced dependence on dephasing rate as a result of the greater possibility of local exciton trapping. Finally, we show that the FMO electronic Hamiltonian is not particularly optimised for EET; instead, it is just one of many possible chromophore organisations which demonstrate a good level of EET transport efficiency following excitation at different chromophores. Overall, these robustness and efficiency characteristics are attributed to the highly connected nature of the chromophore network and the presence of multiple EET pathways, features which might easily be built into artificial photosynthetic systems. PMID- 26374061 TI - Protein search for multiple targets on DNA. AB - Protein-DNA interactions are crucial for all biological processes. One of the most important fundamental aspects of these interactions is the process of protein searching and recognizing specific binding sites on DNA. A large number of experimental and theoretical investigations have been devoted to uncovering the molecular description of these phenomena, but many aspects of the mechanisms of protein search for the targets on DNA remain not well understood. One of the most intriguing problems is the role of multiple targets in protein search dynamics. Using a recently developed theoretical framework we analyze this question in detail. Our method is based on a discrete-state stochastic approach that takes into account most relevant physical-chemical processes and leads to fully analytical description of all dynamic properties. Specifically, systems with two and three targets have been explicitly investigated. It is found that multiple targets in most cases accelerate the search in comparison with a single target situation. However, the acceleration is not always proportional to the number of targets. Surprisingly, there are even situations when it takes longer to find one of the multiple targets in comparison with the single target. It depends on the spatial position of the targets, distances between them, average scanning lengths of protein molecules on DNA, and the total DNA lengths. Physical chemical explanations of observed results are presented. Our predictions are compared with experimental observations as well as with results from a continuum theory for the protein search. Extensive Monte Carlo computer simulations fully support our theoretical calculations. PMID- 26374062 TI - Reproducing kernel potential energy surfaces in biomolecular simulations: Nitric oxide binding to myoglobin. AB - Multidimensional potential energy surfaces based on reproducing kernel interpolation are employed to explore the energetics and dynamics of free and bound nitric oxide in myoglobin (Mb). Combining a force field description for the majority of degrees of freedom and the higher-accuracy representation for the NO ligand and the Fe out-of-plane motion allows for a simulation approach akin to a mixed quantum mechanics/molecular mechanics treatment. However, the kernel representation can be evaluated at conventional force-field speed. With the explicit inclusion of the Fe-out-of-plane (Fe-oop) coordinate, the dynamics and structural equilibrium after photodissociation of the ligand are correctly described compared to experiment. Experimentally, the Fe-oop coordinate plays an important role for the ligand dynamics. This is also found here where the isomerization dynamics between the Fe-ON and Fe-NO state is significantly affected whether or not this co-ordinate is explicitly included. Although the Fe ON conformation is metastable when considering only the bound (2)A state, it may disappear once the (4)A state is included. This explains the absence of the Fe-ON state in previous experimental investigations of MbNO. PMID- 26374063 TI - Thermodynamics of amyloid formation and the role of intersheet interactions. AB - The self-assembly of proteins into beta-sheet-rich amyloid fibrils has been observed to occur with sigmoidal kinetics, indicating that the system initially is trapped in a metastable state. Here, we use a minimal lattice-based model to explore the thermodynamic forces driving amyloid formation in a finite canonical (NVT) system. By means of generalized-ensemble Monte Carlo techniques and a semi analytical method, the thermodynamic properties of this model are investigated for different sets of intersheet interaction parameters. When the interactions support lateral growth into multi-layered fibrillar structures, an evaporation/condensation transition is observed, between a supersaturated solution state and a thermodynamically distinct state where small and large fibril-like species exist in equilibrium. Intermediate-size aggregates are statistically suppressed. These properties do not hold if aggregate growth is one dimensional. PMID- 26374064 TI - Dengue fever. PMID- 26374065 TI - Band-pass processing in a GPCR signaling pathway selects for NFAT transcription factor activation. AB - Many biological processes are rhythmic and proper timing is increasingly appreciated as being critical for development and maintenance of physiological functions. To understand how temporal modulation of an input signal influences downstream responses, we employ microfluidic pulsatile stimulation of a G-protein coupled receptor, the muscarinic M3 receptor, in single cells with simultaneous real-time imaging of both intracellular calcium and NFAT nuclear localization. Interestingly, we find that reduced stimulation with pulses of ligand can give more efficient transcription factor activation, if stimuli are timed appropriately. Our experiments and computational analyses show that M3 receptor induced calcium oscillations form a low pass filter while calcium-induced NFAT translocation forms a high pass filter. The combination acts as a band-pass filter optimized for intermediate frequencies of stimulation. We demonstrate that receptor desensitization and NFAT translocation rates determine critical features of the band-pass filter and that the band-pass may be shifted for different receptors or NFAT dynamics. As an example, we show that the two NFAT isoforms (NFAT4 and NFAT1) have shifted band-pass windows for the same receptor. While we focus specifically on the M3 muscarinic receptor and NFAT translocation, band pass processing is expected to be a general theme that applies to multiple signaling pathways. PMID- 26374066 TI - COLQ variant associated with Devon Rex and Sphynx feline hereditary myopathy. AB - Some Devon Rex and Sphynx cats have a variably progressive myopathy characterized by appendicular and axial muscle weakness, megaesophagus, pharyngeal weakness and fatigability with exercise. Muscle biopsies from affected cats demonstrated variable pathological changes ranging from dystrophic features to minimal abnormalities. Affected cats have exacerbation of weakness following anticholinesterase dosing, a clue that there is an underlying congenital myasthenic syndrome (CMS). A genome-wide association study and whole-genome sequencing suggested a causal variant for this entity was a c.1190G>A variant causing a cysteine to tyrosine substitution (p.Cys397Tyr) within the C-terminal domain of collagen-like tail subunit (single strand of homotrimer) of asymmetric acetylcholinesterase (COLQ). Alpha-dystroglycan expression, which is associated with COLQ anchorage at the motor end-plate, has been shown to be deficient in affected cats. Eighteen affected cats were identified by genotyping, including cats from the original clinical descriptions in 1993 and subsequent publications. Eight Devon Rex and one Sphynx not associated with the study were identified as carriers, suggesting an allele frequency of ~2.0% in Devon Rex. Over 350 tested cats from other breeds did not have the variant. Characteristic clinical features and variant presence in all affected cats suggest a model for COLQ CMS. The association between the COLQ variant and this CMS affords clinicians the opportunity to confirm diagnosis via genetic testing and permits owners and breeders to identify carriers in the population. Moreover, accurate diagnosis increases available therapeutic options for affected cats based on an understanding of the pathophysiology and experience from human CMS associated with COLQ variants. PMID- 26374068 TI - M1 Muscarinic Receptor Deficiency Attenuates Azoxymethane-Induced Chronic Liver Injury in Mice. AB - Cholinergic nervous system regulates liver injury. However, the role of M1 muscarinic receptors (M1R) in modulating chronic liver injury is uncertain. To address this gap in knowledge we treated M1R-deficient and WT mice with azoxymethane (AOM) for six weeks and assessed liver injury responses 14 weeks after the last dose of AOM. Compared to AOM-treated WT mice, M1R-deficient mice had attenuated liver nodularity, fibrosis and ductular proliferation, alpha-SMA staining, and expression of alpha1 collagen, Tgfbeta-R, Pdgf-R, Mmp-2, Timp-1 and Timp-2. In hepatocytes, these findings were associated with reductions of cleaved caspase-3 staining and Tnf-alpha expression. In response to AOM treatment, M1R deficient mice mounted a vigorous anti-oxidant response by upregulating Gclc and Nqo1 expression, and attenuating peroxynitrite generation. M1R-deficient mouse livers had increased expression of Trail-R2, a promotor of stellate cell apoptosis; dual staining for TUNNEL and alpha-SMA revealed increased stellate cells apoptosis in livers from M1R-deficient mice compared to those from WT. Finally, pharmacological inhibition of M1R reduced H2O2-induced hepatocyte apoptosis in vitro. These results indicate that following liver injury, anti oxidant response in M1R-deficient mice attenuates hepatocyte apoptosis and reduces stellate cell activation, thereby diminishing fibrosis. Therefore, targeting M1R expression and activation in chronic liver injury may provide therapeutic benefit. PMID- 26374072 TI - CCR 20th Anniversary Commentary: Simpson's Paradox and Neoadjuvant Trials. AB - The research article by Carey and colleagues, published in the April 15, 2007, issue of Clinical Cancer Research, described the relationship between response to neoadjuvant chemotherapy and outcome by tumor subtype. Today neoadjuvant clinical trials are often designed to provide correlative data to help identify predictive biomarkers or to focus on poor-risk patients identified by residual disease after neoadjuvant treatment. PMID- 26374070 TI - Targeted sequencing reveals clonal genetic changes in the progression of early lung neoplasms and paired circulating DNA. AB - Lungs resected for adenocarcinomas often harbour minute discrete foci of cytologically atypical pneumocyte proliferations designated as atypical adenomatous hyperplasia (AAH). Evidence suggests that AAH represents an initial step in the progression to adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA) and fully invasive adenocarcinoma. Despite efforts to identify predictive markers of malignant transformation, alterations driving this progression are poorly understood. Here we perform targeted next-generation sequencing on multifocal AAHs and different zones of histologic progression within AISs and MIAs. Multiregion sequencing demonstrated different genetic drivers within the same tumour and reveal that clonal expansion is an early event of tumorigenesis. We find that KRAS, TP53 and EGFR mutations are indicators of malignant transition. Utilizing droplet digital PCR, we find alterations associated with early neoplasms in paired circulating DNA. This study provides insight into the heterogeneity of clonal events in the progression of early lung neoplasia and demonstrates that these events can be detected even before neoplasms have invaded and acquired malignant potential. PMID- 26374073 TI - FDA Approval: Blinatumomab. AB - On December 3, 2014, the FDA granted accelerated approval of blinatumomab (Blincyto; Amgen, Inc.) for treatment of Philadelphia chromosome-negative relapsed or refractory precursor B-cell acute lymphoblastic leukemia (R/R ALL). Blinatumomab is a recombinant murine protein that acts as a bispecific CD19 directed CD3 T-cell engager. The basis for the approval was a single-arm trial with 185 evaluable adults with R/R ALL. The complete remission (CR) rate was 32% [95% confidence interval (CI), 26%-40%], and the median duration of response was 6.7 months. A minimal residual disease response was achieved by 31% (95% CI, 25% 39%) of all patients. Cytokine release syndrome and neurologic events were serious toxicities that occurred. Other common (>20%) adverse reactions were pyrexia, headache, edema, febrile neutropenia, nausea, tremor, and rash. Neutropenia, thrombocytopenia, and elevated transaminases were the most common (>10%) laboratory abnormalities related to blinatumomab. A randomized trial is required in order to confirm clinical benefit. PMID- 26374074 TI - Molecular Pathways: At the Crossroads of Cancer Epigenetics and Immunotherapy. AB - Epigenetic regulation allows heritably modulating gene expression profiles without modifying the primary sequence of gDNA. Under physiologic conditions, epigenetic patterns determine tissue-specific gene expression landscapes, gene imprinting, inactivation of chromosome X, and preservation of genomic stability. The most characterized mediators of epigenetic inheritance are gDNA methylation and histone posttranslational modifications that cooperate to alter chromatin state and genome transcription. According to these notions, it is not surprising that cancer cells invariantly deploy epigenetic alterations to achieve gene expression patterns required for neoplastic transformation and tumor progression. In this context, the recently uncovered use of epigenetic alterations by cancer cells to become stealth from the host's immune recognition has significant immunobiologic relevance in tumor progression, and it appears to have potential clinical usefulness. Indeed, immune evasion is among the major obstacles to further improve the efficacy of cancer immunotherapies and to increase long lasting disease control. Luckily, different "epigenetic drugs" able to revert these "epimutations" are available, some of which have already been approved for clinical use. Here, we summarize the immunomodulatory activities of epigenetic drugs that lead to improved immune recognition of cancer cells and focus on the potential of this class of agents in improving the anticancer activity of novel immunotherapies through combinatorial epigenetic immunotherapy approaches. PMID- 26374075 TI - Correction: PID1 (NYGGF4), a New Growth-Inhibitory Gene in Embryonal Brain Tumors and Gliomas. PMID- 26374076 TI - Correction: Replication of Genetic Polymorphisms Reported to Be Associated with Taxane-Related Sensory Neuropathy in Patients with Early Breast Cancer Treated with Paclitaxel-Letter. PMID- 26374077 TI - Quantum Spin Hall States in Stanene/Ge(111). AB - For topological insulators to be implemented in practical applications, it is a prerequisite to select suitable substrates that are required to leave insulators' nontrivial properties and sizable opened band gaps (due to spin-orbital couplings) unaltered. Using ab initio calculations, we predict that Ge(111) surface qualified as a candidate to support stanene sheets, because the band structure of ?3 * ?3 stanene/Ge(111) (2 * 2) surface displays a typical Dirac cone at Gamma point in the vicinity of the Fermi level. Aided with the result of Z2 invariant calculations, a ?3 * ?3 stanene/Ge(111) (2 * 2) system has been proved to sustain the nontrivial topological phase, with the prove being confirmed by the edge state calculations of stanene ribbons. This finding can serve as guidance for epitaxial growth of stanene on substrate and render stanene feasible for practical use as a topological insulator. PMID- 26374079 TI - Children's identification of questions from rising terminal pitch. AB - Young children are slow to master conventional intonation patterns in their yes/no questions, which may stem from imperfect understanding of the links between terminal pitch contours and pragmatic intentions. In Experiment 1, five- to ten-year-old children and adults were required to judge utterances as questions or statements on the basis of intonation alone. Children eight years of age or younger performed above chance levels but less accurately than adult listeners. To ascertain whether the verbal content of utterances interfered with young children's attention to the relevant acoustic cues, low-pass filtered versions of the same utterances were presented to children and adults in Experiment 2. Low-pass filtering reduced performance comparably for all age groups, perhaps because such filtering reduced the salience of critical pitch cues. Young children's difficulty in differentiating declarative questions from statements is not attributable to basic perceptual difficulties but rather to absent or unstable intonation categories. PMID- 26374080 TI - Two-year clinical outcomes following non-surgical mechanical therapy of peri implantitis with adjunctive diode laser application. AB - BACKGROUND: Non-surgical mechanical therapy of peri-implantitis (PI) with/without adjunctive measures yields limited clinical improvements. AIM: To evaluate the clinical outcomes following non-surgical mechanical therapy of PI with adjunctive application of a diode laser after an observation period >=2 years. MATERIAL AND METHODS: At baseline (BL), 15 patients with 23 implants with a sandblasted and acid-etched (SLA) surface diagnosed with PI were enrolled and treated. PI was defined as presence of probing pocket depths (PPD) >=5 mm with bleeding on probing (BoP) and/or suppuration and >=2 threads with bone loss after delivery of the restoration. Implant sites were treated with carbon fiber and metal curettes followed by repeated application of a diode laser 3x for 30 s (settings: 810 nm, 2.5 W, 50 Hz, 10 ms). This procedure was performed at Day 0 (i.e., baseline), 7 and 14. Adjunctive antiseptics or adjunctive systemic antibiotics were not prescribed. RESULTS: All implants were in function after 2 years. The deepest PPD decreased from 7.5 +/- 2.6 mm to 3.6 +/- 0.7 mm at buccal (P < 0.0001) and from 7.7 +/- 2.1 mm to 3.8 +/- 0.9 mm at oral sites (P < 0.0001), respectively. The % of implants with >=1 site with BoP decreased from 100% at BL to 43% after 2 years (P = 0.0002). The % of implants with suppuration decreased from 87% at BL to 0% after 2 years (P < 0.0001). CONCLUSION: Non-surgical mechanical therapy of PI with adjunctive repeated application of a diode laser yielded significant clinical improvements after an observation period of at least 2 years. PMID- 26374081 TI - Evaluation of lanthanide salts as alternative stains to uranyl acetate. AB - Uranyl acetate (UAc) has been generally used not only as a superb staining reagent for ultrathin sections of plastic-embedded biological materials, but also as high-contrast negative stains for biological macromolecules such as particles of protein or virus. However, the use and purchase of radioactive UAc have been restricted. In this study, we determine the performance of ytterbium triacetate, lutetium triacetate, samarium triacetate and gadolinium triacetate as new staining reagents for biological electron microscopy. We observed chemically fixed spinach (Spinacia oleracea) leaves stained with these reagents. Ultrathin sections were stained with these reagents. Some of them were counterstained with lead citrate. The transmission electron microscopy contrast of spinach organelles was evaluated in sections exposed to the conventional stain and new stains. We show acetate salts of samarium, gadolinium, ytterbium and lutetium could be excellent substitutes for UAc for thin section staining and for negative staining. In addition, each reagent showed appreciable negative-staining effects. PMID- 26374083 TI - 1-Alkynyltriazenes as Functional Analogues of Ynamides. AB - The chemical reactivity of 1-alkynyltriazenes has been investigated and is found to parallel the reactivity of ynamides. The similarity in reactivity of these two classes of compounds is demonstrated by addition reactions with acids, by cycloaddition reactions with ketenes, tetracyanoethene, and cyclopropanes, as well as by intramolecular cyclization reactions. The presence of reactive triazene groups in the products enables subsequent transformations. Overall, our results suggest that 1-alkynyltriazenes should become valuable reagents in synthetic organic chemistry. PMID- 26374084 TI - Personality Assessment Screener, Childhood Abuse, and Adult Partner Violence in African American Women Using Primary Care. AB - This study assessed the relationship between psychopathology with the Personality Assessment Screener (PAS) and childhood physical and sexual abuse and adult physical and sexual partner violence in a primary care sample of 98 urban dwelling African American women. Patients completed the PAS, the Childhood Trauma Questionnaire, and the Conflict Tactics Scale. The PAS total score significantly correlated with all measures of childhood and adult abuse. Stepwise regression analyses revealed that PAS element scores of Suicidal Thinking and Hostile Control significantly predicted a history of childhood physical abuse; Suicidal Thinking, Hostile Control, and Acting Out significantly predicted a history of childhood sexual abuse; Suicidal Thinking, Negative Affect, and Alienation significantly predicted current adult partner physical violence; and Psychotic Features, Alcohol Problems, and Anger Control significantly predicted current adult sexual partner violence. The PAS appears to be a useful measure for fast paced primary care settings for identifying patients who need a more thorough assessment for abuse. PMID- 26374085 TI - Fe(III)-Catalyzed Cross-Dehydrogenative Arylation (CDA) between Oxindoles and Arenes under an Air Atmosphere. AB - An efficient Fe(III)-catalyzed cross-dehydrogenative arylation (CDA) of 3 substituted oxindoles with activated arenes under an air atmosphere was developed to provide 3,3'-disubstituted oxindoles in good yields. PMID- 26374086 TI - A novel missense mutation of TNNI2 in a Chinese family cause distal arthrogryposis type 1. AB - The distal arthrogryposis (DA) syndromes are a group of disorders characterized by congenital contractures of limbs. According to phenotypical characteristics, DA syndromes have been clinically classified into 10 types. Currently, at least nine disease causing genes have been identified for different types of DA. Here, we report a 3-generation Chinese pedigree with three DA affected members. We performed whole exome sequencing on two affected and one unaffected individuals of this family and successfully identified a novel missense mutation in TNNI2 as the pathogenic mutation. The TNNI2 gene encodes a subunit of the troponin complex, a contractile machinery of the muscle. The mutation p.F178C that could change the H-bond formation of a neighboring residue occurs at a highly conserved position, suggesting that this variation probably affects the TNNI2 protein function. Our study also demonstrates the power of whole exome sequencing in causal mutation identification for phenotypically variable and genetically heterogeneous disorders. PMID- 26374087 TI - Rehabilitation for patients with myalgic encephalomyelitis/chronic fatigue syndrome: time to extent the boundaries of this field. PMID- 26374088 TI - Margin re-excision and local recurrence in invasive breast cancer: A cost analysis using a decision tree model. AB - BACKGROUND: SSO-ASTRO recently published guidelines defining adequate margins in breast conservation therapy (BCT) as no tumor on ink based on studies demonstrating little difference in local recurrence (LR) with wider margins. We hypothesize that not routinely re-excising close margins results in decreased costs without compromising care. METHODS: A decision tree model was developed for the management of margins after BCT for invasive cancer. Patients were compared among three margin status groups: positive, close (<=2 mm) and negative (>2 mm). Ten publications provided re-excision rates (RER) and LR rates. The model assumed 140,000 BCT/year. Sensitivity analyses determined the most cost-effective strategy. Surgical costs were estimated using 2013 Medicare reimbursement rates. RESULTS: Re-excising close margins was significantly more costly than the alternative, $233.1 million versus $214.3 million, per year in the United States. Total surgical cost was most sensitive to re-excision of close margins-increasing the RER from 0% to 100% resulted in an $18.8 million cost difference. CONCLUSIONS: The strategy of re-excising close margins resulted in a predicted cost of $18.8 million per year. This does not include hospital costs, the cost of surgical complications after re-excision, and underestimates the potential savings by using Medicare reimbursement rates. PMID- 26374089 TI - Reconstruction of cropland cover changes in the Shandong Province over the past 300 years. AB - To advance global change research, it is essential to reconstruct changes in historical cropland coverage on a regional scale in China. This paper presents data collected from 244 local gazetteers, government statistical records and remote-sensing land cover data from the Shandong Province. The study reconstructed the spatial distribution of the rate of reclaimed land at the county level and compared this map with a map of the current spatial distribution of suitable cropland. The following conclusions were drawn: (i) The rate of cultivated land grew exponentially. The extent of reconstruction in cropland areas during the 17(th) century, 18(th)~19(th) centuries, the beginning of the 20(th) century, the 1980 s, and the beginning of the 20(th) century are 4.51 mha, 6.51 mha, 7.52 mha, 8.53 mha and 11.80-12.00 mha, respectively. (ii) Several agricultural centers formed during the late 17(th) century. Until the beginning of the 20(th) century, the reclamation rate increased rapidly near the four southern lakes, which are located in the Zaozhuang and Linyi regions. (iii) Most reclamation activities before the 19(th) century occurred in suitable agricultural areas, and the cultivated land was already reclaimed by the beginning of the 20(th) century. PMID- 26374094 TI - The treatment of gastroparesis, constipation and small intestinal bacterial overgrowth syndrome in patients with Parkinson's disease. AB - INTRODUCTION: Parkinson's disease (PD) affects the nerves of the entire gastrointestinal (GI) tract and may result in profound gastrointestinal (GI) dysfunction leading to poor patient outcomes. Common GI disturbances in patients with PD include gastroparesis (GP), constipation and small intestinal bacterial overgrowth syndrome (SIBO). In particular, GP is difficult to treat due to the limited options available and precautions, contraindications and adverse effects associated with the approved treatments. Moreover, some commonly used medications can worsen pre-existing PD. AREAS COVERED: Our review will focus on treatment options for GP and SIBO with motilin agonists, dopamine receptor antagonists, Ghrelin agonists muscarinic agonists, 5-HT4 receptor agonists, antibiotics, probiotics and herbal formulation such as iberogast. Constipation occurs in the majority of patients with PD and fortunately many treatments are now available. Our review is based on original papers or reviews selected from PUBMED search and Cochrane reviews. EXPERT OPINION: Motility disorders of the GI tract are found frequently in patients with PD and treating the underlying GI disorders caused by PD with various prokinetics and laxatives is paramount in achieving improvements in patient's motor function. Various prokinetics and laxatives are now available to provide some relief of the GI morbidity caused by PD leading even to better absorption of even the PD treatments. PMID- 26374090 TI - Decreased adiposity and enhanced glucose tolerance in shikonin treated mice. AB - OBJECTIVE: Obesity represents a major public health problem, and identifying natural compounds that modulate energy balance and glucose homeostasis is of interest for combating obesity and its associated disorders. The naphthoquinone shikonin has diverse beneficial properties including anti-inflammatory, anti oxidant, and anti-microbial effects. The objective of this study is to investigate the effects of shikonin on adiposity and glucose homeostasis. METHODS: The metabolic effects of shikonin treatment on mice fed regular chow or challenged with a high-fat diet (HFD) were determined. RESULTS: Shikonin treated mice fed regular chow exhibited improved glucose tolerance compared with controls. In addition, shikonin treated mice fed HFD displayed decreased weight gain and resistance to HFD-induced glucose intolerance. Further, shikonin treatment decreased HFD-induced hepatic dyslipidemia. These findings correlated with enhanced hepatic insulin signaling in shikonin treated mice as evidenced by increased tyrosyl phosphorylation of the insulin receptor and enhanced downstream signaling. CONCLUSIONS: These studies identify shikonin as a potential regulator of systemic glucose tolerance, energy balance, and adiposity in vivo. PMID- 26374095 TI - Microsurgical Anatomy of the Terminal Hypoglossal Nerve Relevant for Neurostimulation in Obstructive Sleep Apnea. AB - BACKGROUND: Neurostimulation of the hypoglossal nerve has shown promising results in the treatment of obstructive sleep apnea. This anatomic study describes the detailed topography of the hypoglossal nerve's motor points as a premise for super-selective neurostimulation in order to optimize results and minimize the risk of complications related to main nerve trunk manipulation. METHODS: Thirty cadaveric hypoglossal nerves were dissected and characterized by number of branches, arborization pattern, and terminal branch motor point location. For each motor point, the distance to cervical midline (x axis), distance to posterior aspect of the symphysis (y axis), and depth from the plane formed by the inferior border of symphysis and anterior border of hyoid (z axis) were recorded. RESULTS: The average number of distal branches for each hypoglossal nerve was found to be 9.95 +/- 2.28. The average number of branches per muscle was found to be 3.3 +/- 1.5 for the hyoglossus muscle, 1.8 +/- 0.9 for the geniohyoid muscle, and 5.0 +/- 1.6 for the genioglossus muscle. It was found that branches to the genioglossus and geniohyoid muscles were located closer to midline (relative lengths of 0.19 +/- 0.07 and 0.19 +/- 0.05, respectively) while hyoglossus branches were located more laterally (0.38 +/- 0.10 relative length). On the y-axis, the branches to the genioglossus were the most anterior and therefore closest to the posterior symphysis of the mandible (relative length of 0.48 +/- 0.11), followed by the geniohyoid (0.66 +/- 0.09), and the hyoglossus (0.76 +/- 0.16). The branches to the geniohyoid were the most superficial (relative length of 0.26 +/- 0.06), followed by the genioglossus (0.36 +/- 0.09), and finally, the hyoglossus branches (0.47 +/- 0.11), which were located deeply. CONCLUSION: A topographical map of the hypoglossal nerve terminal motor points was successfully created and could provide a framework for the optimization of the neurostimulation techniques. PMID- 26374096 TI - Apolipoprotein E polymorphism in aneurysmal subarachnoid haemorrhage in West Sweden. AB - BACKGROUND AND PURPOSE: Aneurysmal subarachnoid haemorrhage (aSAH) is associated with high morbidity and mortality despite novel treatments. Genetic variability may explain outcome differences. Apolipoprotein E (ApoE) is a glycoprotein with a major role in brain lipoprotein metabolism. It has three isoforms encoded by distinct alleles: APOEepsilon2, APOEepsilon3 and APOEepsilon4. The APOEepsilon4 allele is associated with Alzheimer's disease and worse outcome after traumatic brain injury and ischaemic stroke. This prospective blinded study explored the influence of the APOEepsilon4 polymorphism on the risk of aSAH, risk of cerebral vasospasm (CVS) and 1-year neurological outcome. METHODS: The APOEpsilonepsilon4 polymorphism was analysed in 147 patients with aSAH. Allele and genotype frequencies were compared to those found in a gender- and area-matched control group of healthy individuals (n = 211). Early CVS was identified and treated according to neurointensive care unit (NICU) guidelines. Neurological deficit(s) at admittance and at 1-year follow-up visit was recorded. Neurological outcome was assessed by the National Institute of Health Stroke Scale, Barthel Index and the Extended Glasgow Outcome Scale. RESULTS: APOEepsilon4 and non-APOEepsilon4 allele frequencies were similar in aSAH patients and healthy individuals. The presence of APOEepsilon4 was not associated with the development of early CVS. We could not find an influence of the APOE polymorphism on 1-year neurological outcome between groups. Subgroup analyses of patients treated with surgical clipping vs endovascular coiling did not reveal any associations. CONCLUSIONS: The APOEepsilon4 polymorphism has no major influence on risk of aSAH, the occurrence of CVS or long-term neurological outcome after aSAH. PMID- 26374097 TI - Selective polymerization catalysis: controlling the metal chain end group to prepare block copolyesters. AB - Selective catalysis is used to prepare block copolyesters by combining ring opening polymerization of lactones and ring-opening copolymerization of epoxides/anhydrides. By using a dizinc complex with mixtures of up to three different monomers and controlling the chemistry of the Zn-O(polymer chain) it is possible to select for a particular polymerization route and thereby control the composition of block copolyesters. PMID- 26374099 TI - Impact of delays in definitive treatment on overall survival: a National Cancer Database study of patients with Hodgkin lymphoma. AB - The purpose of this large observational study was to examine outcomes in patients with Hodgkin lymphoma (HL) by timing to definitive chemotherapy (TTC) using standard and propensity score (PS)-adjusted Cox proportional hazards models. From 1998-2011, 56,457 patients with stage I-IV HL were studied, with a median follow up of 6.0 years (median age=39). Median TTC was 26 days from diagnosis. The cohort of "early" (<60 days from diagnosis) TTC patients included 45,307 (80.3%) patients and "late" (>=60 days) TTC was 11,150 (19.7%). Patients were more likely to experience early TTC if they were of a younger age, at an advanced stage, with "B" symptoms, favorably insured, favorable socioeconomic status, and treated at comprehensive cancer center (all p<0.05). Ten-year overall survival for patients with early TTC was 73.2% vs. 70.0% for those with late TTC (HR=0.87; 95%CI, 0.83 0.92, p<0.0001). After PS-matching for co-variates, early TTC was not associated with overall survival (HR=0.96; 95%CI, 0.85-1.08, p=0.51). This represents the only study to evaluate overall survival by time to definitive treatment for HL. PMID- 26374098 TI - CPAG: software for leveraging pleiotropy in GWAS to reveal similarity between human traits links plasma fatty acids and intestinal inflammation. AB - Meta-analyses of genome-wide association studies (GWAS) have demonstrated that the same genetic variants can be associated with multiple diseases and other complex traits. We present software called CPAG (Cross-Phenotype Analysis of GWAS) to look for similarities between 700 traits, build trees with informative clusters, and highlight underlying pathways. Clusters are consistent with pre defined groups and literature-based validation but also reveal novel connections. We report similarity between plasma palmitoleic acid and Crohn's disease and find that specific fatty acids exacerbate enterocolitis in zebrafish. CPAG will become increasingly powerful as more genetic variants are uncovered, leading to a deeper understanding of complex traits. CPAG is freely available at www.sourceforge.net/projects/CPAG/. PMID- 26374101 TI - Erratum: Randomized controlled trial on drowning prevention for parents with children aged below five years in Bangladesh: a study protocol. PMID- 26374100 TI - Kaposi's sarcoma: a 10-year experience with 248 patients at a single tertiary care hospital in Tanzania. AB - BACKGROUND: Kaposi's Sarcoma is the most common sarcoma and second most prevalent cancer seen in Tanzania. Little is known about Kaposi's sarcoma in our setting as there is paucity of recent published data regarding this condition. This study describes the clinicopathological pattern and treatment outcome of Kaposi's sarcoma at Bugando Medical Centre, a tertiary care hospital in northwestern Tanzania. METHODS: This was a prospective study of histologically confirmed Kaposi's sarcoma that was conducted at Bugando Medical Center between July 2004 and June 2014. RESULTS: A total of 248 patients (M:F = 1.4:1) representing 2.4% of all malignancies during the study period were enrolled into the study. The median age at presentation was 36 years. Females were younger than males (p = 0.04). Out of 248 patients, 122 (49.2%) were HIV positive. Of these, 46 (37.7%) were males and 76 (62.3%) females. AIDS-related Kaposi's sarcoma were younger than HIV negative Kaposi's sarcoma patients (p = 0.011). Median duration of symptoms was 6 months. Kaposi's sarcoma was the AIDS defining disease in 82 (67.2%) patients while in the remaining 40 (32.8%) it was diagnosed between 1 and 14 months after the initial diagnosis of AIDS. The lower limb was most frequently involved site in 28.9% of patient. Females had more disseminated lesions compared with more localized lesions in the males (p = 0.001). The treatment modalities in this study included chemotherapy, radiotherapy, surgery and highly active antiretroviral therapy. Overall 126 (53.4%) patients had significant improvement in quality of life at the end of 1 year follow up. Treatment related complication and mortality rates were 25.8 and 24.2% respectively. Poor ACTG stage, CD4+ count <200 cells/ul, associated co-morbid illness, disseminated disease and poor adherent to chemotherapy were the significant independent factors associated with deaths (p < 0.001). Patient's follow-up was generally poor and data on long-term survivals were not available as more than two-thirds of patients were lost to follow up. CONCLUSION: Kaposi's sarcoma is the most common malignant vascular tumor and HIV/AIDS- related cancer in our region. There is an urgent need to develop health education programmes to enhance the understanding of this disease and how it spreads, particularly among the younger generation. PMID- 26374102 TI - Evaluation of inhibition of F4ac positive Escherichia coli attachment with xanthine dehydrogenase, butyrophilin, lactadherin and fatty acid binding protein. AB - BACKGROUND: Neonatal and post-weaning colibacillosis caused by enterotoxigenic E. coli is responsible for substantial economic losses encountered by the pork industry. Intestinal colonization of young piglets by E. coli depends on the efficiency of bacterial attachment to host gastrointestinal epithelium that is mediated by fimbriae. We tested the effect of porcine individual milk fat globule membrane (MFGM) proteins on F4ac positive E. coli attachment to porcine enterocytes in vitro. RESULTS: Butyrophilin, lactadherin and fatty acid binding protein inhibited fimbriae-dependent adherence of E. coli to enterocytes in vitro, while xanthine dehydrogenase did not. The inhibiting activity was dose dependent for all three proteins, but the inhibiting efficiency was different. CONCLUSIONS: The results indicate that MFGM proteins may interfere with attachment of E. coli to porcine neonatal intestinal mucosa. PMID- 26374103 TI - Copy number alterations detected by whole-exome and whole-genome sequencing of esophageal adenocarcinoma. AB - BACKGROUND: Esophageal adenocarcinoma (EA) is among the leading causes of cancer mortality, especially in developed countries. A high level of somatic copy number alterations (CNAs) accumulates over the decades in the progression from Barrett's esophagus, the precursor lesion, to EA. Accurate identification of somatic CNAs is essential to understand cancer development. Many studies have been conducted for the detection of CNA in EA using microarrays. Next-generation sequencing (NGS) technologies are believed to have advantages in sensitivity and accuracy to detect CNA, yet no NGS-based CNA detection in EA has been reported. RESULTS: In this study, we analyzed whole-exome (WES) and whole-genome sequencing (WGS) data for detecting CNA from a published large-scale genomic study of EA. Two specific comparisons were conducted. First, the recurrent CNAs based on WGS and WES data from 145 EA samples were compared to those found in five previous microarray based studies. We found that the majority of the previously identified regions were also detected in this study. Interestingly, some novel amplifications and deletions were discovered using the NGS data. In particular, SKI and PRKCZ detected in a deletion region are involved in transforming growth factor-beta pathway, suggesting the potential utility of novel biomarkers for EA. Second, we compared CNAs detected in WGS and WES data from the same 15 EA samples. No large scale CNA was identified statistically more frequently by WES or WGS, while more focal-scale CNAs were detected by WGS than by WES. CONCLUSIONS: Our results suggest that NGS can replace microarrays to detect CNA in EA. WGS is superior to WES in that it can offer finer resolution for the detection, though if the interest is on recurrent CNAs, WES can be preferable to WGS for its cost effectiveness. PMID- 26374104 TI - Impact of medication adherence on renal function in comorbid patients with type 2 diabetes and depression: protocol for a cohort study. AB - BACKGROUND: Prevention, or slowing the progression, of diabetic nephropathy is one of the important goals in diabetes care. Although the impact of depression is a concern in patients with diabetes, it is unknown whether there is an association between adherence to hypoglycemic medication and the decline of renal function in comorbid patients with diabetes and depression. We will conduct a cohort study aimed at examining (1) depression as a predictor of renal function decline, and (2) how adherence to hypoglycemic medication relates to depression and renal function decline in patients with type 2 diabetes. METHODS/DESIGN: In this multicenter cohort study, 550 patients with type 2 diabetes aged 20 years and older will be recruited at 20 outpatient clinics in general medicine and psychiatry. We will measure depression (Patient Health Questionnaire), medication adherence (medication possession ratio, Morisky Medication Adherence Scale, and one-item hypoglycemic medication adherence scale), and renal function (urinary albumin-creatinine ratio and estimated glomerular filtration rate) at baseline and at the 12-month follow-up. The primary endpoint is decline of renal function at 12 months. The secondary endpoints include clinical variables, quality of life, and the attitude of professionals toward depression. We will perform multivariable linear regression analysis to evaluate the effects of medication adherence on the decline of renal function in comorbid patients with type 2 diabetes and depression. DISCUSSION: To our knowledge, this will be the first study to examine how adherence to hypoglycemic medication relates to the decline of renal function in comorbid patients with type 2 diabetes and depression. The results of the study will have implications for practitioners of diabetes care, policy makers, and researchers for the prevention and treatment of diabetic nephropathy. TRIAL REGISTRATION: UMIN000017513 (Registered on May 22, 2015). PMID- 26374106 TI - Ensuring quality in postgraduate medical education: competency testing is the key. AB - The changes made to the curricula and assessment systems in the UK have resulted in pathology specialty-training programmes which assess trainees on a regular (weekly or monthly) basis. An end of first year assessment tests their aptitude for the specialty, the FRCPath examinations taking place after at least one to two (part 1) and three to four (part 2) years of training respectively, and multi source feedback is undertaken in years 1, 3 and 5. With regular educational appraisal, this constitutes cohorts of well-assessed and supported trainees. The assessments are blueprinted to the curriculum, ensuring adequate assessment coverage of curriculum content within workplace-based assessments (WPBA), objective structured pathology examinations and the FRCPath examinations. Notably, generic non-clinical attributes and behavioural skills such as leadership and management skills can be covered in the WPBA. Many of these changes are evolutionary in nature, but some have been imposed by continuously increasing regulatory requirements. Whilst additional information is generated, the increased amount of assessment of trainees has led to complaints that trainees do not acquire enough practical experience in the laboratory. It will be important to find the balance between didactic teaching with formal assessment, and apprenticeship-style, practical hands-on learning. PMID- 26374107 TI - Widening the path and window of opportunity for FDA approval of non-vitamin K oral anticoagulant specific antidotes and reversal agents. AB - There remains a need for safe, immediately effective, and easy to administer antidotes for patients taking novel oral anticoagulants (NOACs) in the settings of major bleeding, need for emergency surgery, and accidental overdose. We review considerations for the successful safety and effectiveness evaluation of potential antidotes currently under development. These compounds are in expedited regulatory approval programs aimed at accelerating the preclinical and clinical evaluation and approval processes for treatments of serious conditions. We review the features of these expedited programs as well as the FDA's efforts to broadly advance the efficiency of drug development and increase the number of new compounds brought to market. The critical path initiative and regulatory science initiative have resulted in numerous successful programs to address current challenges such as a paucity of validated biomarkers and surrogate endpoints as well as unreliable animal models of toxicity. The FDA has also advocated for increased use of pharmacokinetic/pharmacodynamic modeling and adaptive trial design. These efforts foster collaboration between academia, industry and the public sector across interdisciplinary sciences and may continue to widen the pathway for NOAC-specific reversal agents and other novel compounds. PMID- 26374109 TI - The Tree of Sirtuins and the Garden of Cardiovascular Youth. AB - Sirtuins (SIRTs) are a class of nicotine adenine dinucleotide (NAD+)-dependent proteins which participate in numerous molecular pathways involved in various age related human diseases, such as type II diabetes, cardiovascular (CV) diseases and cancer. They have a major role in apoptosis, inflammation, oxidative stress and metabolism regulation, traits that have a great impact on CV physiology and pathology. Their unique profile of NAD+ energy dependency makes them an appealing target for human intervention in cellular and metabolic processes. This review focuses on the recent advances of SIRTs research aiming to shed light on the emerging roles of SIRTs in the pathophysiology of CV and metabolic diseases. PMID- 26374108 TI - The Pharmacogenomics of Anti-Platelet Intervention (PAPI) Study: Variation in Platelet Response to Clopidogrel and Aspirin. AB - Clopidogrel and aspirin are commonly prescribed anti-platelet medications indicated for patients who have experienced, or are at risk for, ischemic cardiovascular events. The Pharmacogenomics of Anti-Platelet Intervention (PAPI) Study was designed to characterize determinants of clopidogrel and dual anti platelet therapy (DAPT) response in a healthy cohort of Old Order Amish from Lancaster, PA. Following a loading dose, clopidogrel was taken once a day for 7 days. One hour after the last dose of clopidogrel, 325 mg of aspirin was given. Ex vivo platelet aggregometry was performed at baseline, post-clopidogrel, and post-DAPT. Platelet aggregation measurements were significantly lower after both interventions for all agonists tested (p <0.05), although there was large inter individual variation in the magnitude of anti-platelet response. Female sex and older age were associated with higher platelet aggregation at all three time points. Change in aggregation was correlated among the various agonists at each time point. Heritability (h2) of change in platelet aggregation was significant for most traits at all time-points (range h2=0.14-0.57). Utilization of a standardized, short-term intervention provided a powerful approach to investigate sources of variation in platelet aggregation response due to drug therapy. Further, this short-term intervention approach may provide a useful paradigm for pharmacogenomics studies. PMID- 26374110 TI - Diabetes Mellitus, Hypertension and Hypercholesterolemia in Relation to the 10 Year ACS Prognosis; the GREECS Study. AB - Although hypertension, hypercholesterolemia and diabetes mellitus (DM) are recognized as major cardio-metabolic risk factors in primary Acute Coronary Syndrome (ACS) prevention, studies focusing on secondary ACS incidence are scarce. In the present study, the association between the aforementioned factors and 10-year ACS prognosis was evaluated. From October 2003 to September 2004 2,172 consecutive patients with ACS diagnosis, from 6 Greek hospitals, were enrolled. During 2013-14, the 10-year follow-up was performed in 1,918 participants. Baseline clinical factors were assessed through physical examination, medical records and pharmacological management. All-cause mortality and the development of fatal or non-fatal ACS events were recorded through medical records or hospital registries. Logistic regression models were applied to evaluate the impact of baseline clinical status on the ACS prognosis. The 10 year all cause and ACS mortality rate was 32.6 and 17.8%, respectively. Multi adjusted analysis highlighted that, after taking into account various potential confounders, DM was the sole clinical factor associated with adverse effect on the 10-year ACS fatal incidence [Odds Ratio (OR)=1.35, 95% Confidence Interval (95% CI) 1.01, 1.80, p=0.04]. DM was the only clinical factor that aggravated ACS prognosis, whereas abnormal lipids profile and blood pressure did not seem to determine prognosis. Thus, glycaemic control may play a critical role in the secondary CVD prevention management of ACS patients. PMID- 26374111 TI - Tacrolimus trough-level variability predicts long-term allograft survival following kidney transplantation. AB - AIMS: The purpose of this study is to investigate tacrolimus trough-level variability from 3 to 12 months following transplantation and its association with allograft survival in renal transplant recipients. MATERIALS AND METHODS: In this observational cohort study, tacrolimus trough-level variability was used as the predictor of all-cause allograft failure (defined as return to dialysis) and patient survival (all-cause mortality). RESULTS: In total, 394 transplants were included in the analysis. Sixty-two transplants failed during the study. Tacrolimus trough-level variability across quartile groups were: Q1 median variability 12.5 %, range 4.76-15.71 % (n = 99), Q2 median variability 18.17 %, range 15.74-21.29 % (n = 96), Q3 median variability 24.63 % range 21.42-28.88 % (n = 100), Q4 median variability 36.91 %, range 28.91-81.9 % (n = 99). Higher tacrolimus trough-level variability was associated with inferior allograft survival in univariate models [hazard ratio per quartile increase (HR), 1.46, 95 % CI 1.16-1.83, p value = 0.001] and multivariate models (HR 1.36, 95 % CI 1.05 1.78, p value = 0.019). Higher tacrolimus trough-level variability was not associated with patient survival; univariate model (HR 1.25, 95 % CI 0.90-1.74, p value = 0.17), multivariate model (HR 1.25, 95 % CI 0.86-1.83, p value = 0.23). CONCLUSIONS: Inferior renal allograft survival was observed in recipients with higher variability in tacrolimus trough-levels. PMID- 26374114 TI - Comparison of intra-articular bupivacaine-morphine with bupivacaine-tenoxicam combinations on post-operative analgesia in patients with arthroscopic meniscectomy: a prospective, randomised study. AB - AIM: There are many alternatives for post-operative pain relief in patients who have had general anaesthesia. The aim of this study was to evaluate the efficacy of intra-articular bupivacaine + morphine and bupivacaine + tenoxicam applications in post-operative pain control in patients undergoing knee arthroscopy with general anaesthesia. METHOD: This was a prospective study. Standard anaesthesia procedures were applied to each patient, and the 240 patients chosen at random were then divided into two groups. Each group received a different combination of drugs for this double-blind study. The first group (group A: 120 patients) received 0.5% bupivacaine 100 mg + tenoxicam 20 mg (22 ml); the second group (group B) received 0.5% bupivacaine 100 mg + morphine 2 mg (22 ml); both groups received their drugs at the end of the intra-articular operation before tourniquet deflation. Before the operation, patients were asked about their post-operative pain at particular periods over the following 24 hours using the visual analogue scale (VAS) and the numeric rating scale (NRS). An additional analgaesic requirement and possible side effects were also recorded. RESULTS: Group A patients needed analgaesics sooner after operation than patients in group B. In Group B, VAS and NRS values were statistically higher compared with group A at the 12th hour. There were also fewer side effects seen in group A versus group B. CONCLUSION: Effective and reliable results were obtained in post operative pain control in bupivacaine added to the morphine or tenoxicam groups following arthroscopic meniscectomy. In the tenoxicam group, patients reported less pain, fewer side effects and less need for analgesics at 12 hours after the operation. LEVEL OF EVIDENCE: level 1, therapeutic, randomised, multicentric study. PMID- 26374115 TI - Predicting loss of height in surgically treated displaced intra-articular fractures of the calcaneus. AB - PURPOSE: The goal of calcaneal fracture surgery is to restore its anatomy and good foot function. However, loss of height of the subtalar joint can occur post operatively, as expressed by a decrease in Bohler's angle (BA). The aim of this study was to identify potential factors associated with a post-operative decrease in BA. METHODS: All consecutive adult patients treated with open reduction and internal fixation (ORIF) by an extended lateral approach (ELA) between 2000 and 2013 were retrospectively included. Primary outcome was the occurrence of a calcaneal collapse, defined as a postoperative decrease of >=10 degrees in BA. The BA was measured pre-operatively, directly following surgery and at one year follow-up. Patient characteristics (body mass index, diabetes mellitus, smoking/alcohol/substance abuse, American Society of Anaesthesiologist classification), fracture classification and treatment characteristics: per operative increase in BA and occurrence of post-operative wound infection (POWI) were collected. RESULTS: A total of 262 patients with 276 calcaneal fractures were included. A calcaneal collapse occurred in 46 cases (17%). The median preoperative BA, per-operative increase in BA and post-operative decrease in BA were, respectively, 2 degrees , 27 degrees and 4 degrees . A calcaneal collapse was seen more often following a per-operative increase of >25 degrees in BA, but no significant association was found (p = 0.056). Uni- and multivariate analysis showed that patients with substance abuse and those with POWI had significantly more calcaneal collapse (p < 0.05). No association was found between substance abuse and the occurrence of POWI (p = 0.293). CONCLUSIONS: In nearly one in six patients with an intra-articular calcaneal fracture treated with ORIF by an ELA, a post-operative collapse of >=10 degrees was found during follow-up. Calcaneal collapse was correlated with the occurrence of a POWI and substance abuse. PMID- 26374116 TI - The food supplement coenzyme Q10 and suppression of antitubercular drug-induced hepatic injury in rats: the role of antioxidant defence system, anti-inflammatory cytokine IL-10. AB - INTRODUCTION: Isoniazid (INH) and rifampicin (RIF), the most common anti tubercular therapy, causes hepatotoxicity through a multi-step mechanism in certain individuals. The present study was an attempt to evaluate the hepatoprotective effect of coenzyme Q10 against INH + RIF-induced hepatotoxicity in Wistar albino rats. METHODS: Hepatotoxicity was induced by the oral administration of INH + RIF (50 mg/kg b.w. each/day) in normal saline water for 28 days. The hepatoprotective effect of coenzyme Q10 (10 mg/kg b.w./day) was compared with that of the standard drug silymarin (25 mg/kg b.w./day). Animals were sacrificed at the end of the study period, and blood and liver were collected for biochemical, immunological and histological analyses. RESULTS: Evaluation of biochemical parameters showed that coenzyme Q10 treatment caused significant (P < 0.05) reduction in the elevated levels of serum liver function markers and restored normal levels of total protein, albumin and lipids in INH + RIF-treated rats. Also, it was observed that coenzyme Q10 was able to restore normal levels of enzymic antioxidants, reduced glutathione and lipid peroxidation in the INH + RIF-treated rats. Coenzyme Q10 was found to effectively reduce the extent of liver damage caused due to INH + RIF. In addition, the levels of IL-10 and IL-6 were significantly elevated in the INH + RIF-induced rats treated with CoQ10. CONCLUSION: Our study indicates the protective role of coenzyme Q10 in attenuating the hepatotoxic effects of INH + RIF in a rat model and that it could be used as a food supplement during anti-tubercular therapy. PMID- 26374113 TI - Current Neurogenic and Neuroprotective Strategies to Prevent and Treat Neurodegenerative and Neuropsychiatric Disorders. AB - The adult central nervous system is commonly known to have a very limited regenerative capacity. The presence of functional stem cells in the brain can therefore be seen as a paradox, since in other organs these are known to counterbalance cell loss derived from pathological conditions. This fact has therefore raised the possibility to stimulate neural stem cell differentiation and proliferation or survival by either stem cell replacement therapy or direct administration of neurotrophic factors or other proneurogenic molecules, which in turn has also originated regenerative medicine for the treatment of otherwise incurable neurodegenerative and neuropsychiatric disorders that take a huge toll on society. This may be facilitated by the fact that many of these disorders converge on similar pathophysiological pathways: excitotoxicity, oxidative stress, neuroinflammation, mitochondrial failure, excessive intracellular calcium and apoptosis. This review will therefore focus on the most promising achievements in promoting neuroprotection and neuroregeneration reported to date. PMID- 26374117 TI - Two Essential Light Chains Regulate the MyoA Lever Arm To Promote Toxoplasma Gliding Motility. AB - Key to the virulence of apicomplexan parasites is their ability to move through tissue and to invade and egress from host cells. Apicomplexan motility requires the activity of the glideosome, a multicomponent molecular motor composed of a type XIV myosin, MyoA. Here we identify a novel glideosome component, essential light chain 2 (ELC2), and functionally characterize the two essential light chains (ELC1 and ELC2) of MyoA in Toxoplasma. We show that these proteins are functionally redundant but are important for invasion, egress, and motility. Molecular simulations of the MyoA lever arm identify a role for Ca(2+) in promoting intermolecular contacts between the ELCs and the adjacent MLC1 light chain to stabilize this domain. Using point mutations predicted to ablate either the interaction with Ca(2+) or the interface between the two light chains, we demonstrate their contribution to the quality, displacement, and speed of gliding Toxoplasma parasites. Our work therefore delineates the importance of the MyoA lever arm and highlights a mechanism by which this domain could be stabilized in order to promote invasion, egress, and gliding motility in apicomplexan parasites. IMPORTANCE: Tissue dissemination and host cell invasion by apicomplexan parasites such as Toxoplasma are pivotal to their pathogenesis. Central to these processes is gliding motility, which is driven by an actomyosin motor, the MyoA glideosome. Others have demonstrated the importance of the MyoA glideosome for parasite motility and virulence in mice. Disruption of its function may therefore have therapeutic potential, and yet a deeper mechanistic understanding of how it works is required. Ca(2+)-dependent and -independent phosphorylation and the direct binding of Ca(2+) to the essential light chain have been implicated in the regulation of MyoA activity. Here we identify a second essential light chain of MyoA and demonstrate the importance of both to Toxoplasma motility. We also investigate the role of Ca(2+) and the MyoA regulatory site in parasite motility and identify a potential mechanism whereby binding of a divalent cation to the essential light chains could stabilize the myosin to allow productive movement. PMID- 26374118 TI - Effect of Serotype on Pneumococcal Competition in a Mouse Colonization Model. AB - Competitive interactions between Streptococcus pneumoniae strains during host colonization could influence the serotype distribution in nasopharyngeal carriage and pneumococcal disease. We evaluated the competitive fitness of strains of serotypes 6B, 14, 19A, 19F, 23F, and 35B in a mouse model of multiserotype carriage. Isogenic variants were constructed using clinical strains as the capsule gene donors. Animals were intranasally inoculated with a mixture of up to six pneumococcal strains of different serotypes, with separate experiments involving either clinical isolates or isogenic capsule-switch variants of clinical strain TIGR4. Upper-respiratory-tract samples were repeatedly collected from animals in order to monitor changes in the serotype ratios using quantitative PCR. A reproducible hierarchy of capsular types developed in the airways of mice inoculated with multiple strains. Serotype ranks in this hierarchy were similar among pneumococcal strains of different genetic backgrounds in different strains of mice and were not altered when tested under a range of host conditions. This rank correlated with the measure of the metabolic cost of capsule synthesis and in vitro measure of pneumococcal cell surface charge, both parameters considered to be predictors of serotype-specific fitness in carriage. This study demonstrates the presence of a robust competitive hierarchy of pneumococcal serotypes in vivo that is driven mainly, but not exclusively, by the capsule itself. IMPORTANCE: Streptococcus pneumoniae (pneumococcus) is the leading cause of death due to respiratory bacterial infections but also a commensal frequently carried in upper airways. Available vaccines induce immune responses against polysaccharides coating pneumococcal cells, but with over 90 different capsular types (serotypes) identified, they can only target strains of the selected few serotypes most prevalent in disease. Vaccines not only protect vaccinated individuals against disease but also protect by reducing carriage of vaccine-targeted strains to induce herd effects across whole populations. Unfortunately, reduction in the circulation of vaccine-type strains is offset by increase in carriage and disease from nonvaccine strains, indicating the importance of competitive interactions between pneumococci in shaping the population structure of this pathogen. Here, we showed that the competitive ability of pneumococcal strains to colonize the host strongly depends on the type of capsular polysaccharide expressed by pneumococci and only to a lesser degree on strain or host genetic backgrounds or on variation in host immune responses. PMID- 26374120 TI - Erratum for Nell et al., Dynamics of Lewis b Binding and Sequence Variation of the babA Adhesin Gene during Chronic Helicobacter pylori Infection in Humans. PMID- 26374119 TI - Epigenetics and Proteomics Join Transcriptomics in the Quest for Tuberculosis Biomarkers. AB - An estimated one-third of the world's population is currently latently infected with Mycobacterium tuberculosis. Latent M. tuberculosis infection (LTBI) progresses into active tuberculosis (TB) disease in ~5 to 10% of infected individuals. Diagnostic and prognostic biomarkers to monitor disease progression are urgently needed to ensure better care for TB patients and to decrease the spread of TB. Biomarker development is primarily based on transcriptomics. Our understanding of biology combined with evolving technical advances in high throughput techniques led us to investigate the possibility of additional platforms (epigenetics and proteomics) in the quest to (i) understand the biology of the TB host response and (ii) search for multiplatform biosignatures in TB. We engaged in a pilot study to interrogate the DNA methylome, transcriptome, and proteome in selected monocytes and granulocytes from TB patients and healthy LTBI participants. Our study provides first insights into the levels and sources of diversity in the epigenome and proteome among TB patients and LTBI controls, despite limitations due to small sample size. Functionally the differences between the infection phenotypes (LTBI versus active TB) observed in the different platforms were congruent, thereby suggesting regulation of function not only at the transcriptional level but also by DNA methylation and microRNA. Thus, our data argue for the development of a large-scale study of the DNA methylome, with particular attention to study design in accounting for variation based on gender, age, and cell type. IMPORTANCE: DNA methylation modifies the transcriptional program of cells. We have focused on two major populations of leukocytes involved in immune response to infectious diseases, granulocytes and monocytes, both of which are professional phagocytes that engulf and kill bacteria. We have interrogated how DNA methylation, gene expression, and protein translation differ in these two cell populations between healthy individuals and patients suffering from TB. To better understand the underlying biologic mechanisms, we harnessed a statistical enrichment analysis, taking advantage of predefined and well-characterized gene sets. Not only were there clear differences on various levels between the two populations, but there were also differences between TB patients and healthy controls in the transcriptome, proteome, and, for the first time, DNA methylome in these cells. Our pilot study emphasizes the value of a large-scale study of the DNA methylome taking into account our findings. PMID- 26374121 TI - Colletotrichum orbiculare FAM1 Encodes a Novel Woronin Body-Associated Pex22 Peroxin Required for Appressorium-Mediated Plant Infection. AB - The cucumber anthracnose fungus Colletotrichum orbiculare forms specialized cells called appressoria for host penetration. We identified a gene, FAM1, encoding a novel peroxin protein that is essential for peroxisome biogenesis and that associates with Woronin bodies (WBs), dense-core vesicles found only in filamentous ascomycete fungi which function to maintain cellular integrity. The fam1 disrupted mutants were unable to grow on medium containing oleic acids as the sole carbon source and were nonpathogenic, being defective in both appressorium melanization and host penetration. Fluorescent proteins carrying peroxisomal targeting signals (PTSs) were not imported into the peroxisomes of fam1 mutants, suggesting that FAM1 is a novel peroxisomal biogenesis gene (peroxin). FAM1 did not show significant homology to any Saccharomyces cerevisiae peroxins but resembled conserved filamentous ascomycete-specific Pex22-like proteins which contain a predicted Pex4-binding site and are potentially involved in recycling PTS receptors from peroxisomes to the cytosol. C. orbiculare FAM1 complemented the peroxisomal matrix protein import defect of the S. cerevisiae pex22 mutant. Confocal microscopy of Fam1-GFP (green fluorescent protein) fusion proteins and immunoelectron microscopy with anti-Fam1 antibodies showed that Fam1 localized to nascent WBs budding from peroxisomes and mature WBs. Association of Fam1 with WBs was confirmed by colocalization with WB matrix protein CoHex1 (C. orbiculare Hex1) and WB membrane protein CoWsc (C. orbiculare Wsc) and by subcellular fractionation and Western blotting with antibodies to Fam1 and CoHex1. In WB-deficient cohex1 mutants, Fam1 was redirected to the peroxisome membrane. Our results show that Fam1 is a WB-associated peroxin required for pathogenesis and raise the possibility that localized receptor recycling occurs in WBs. IMPORTANCE: Colletotrichum orbiculare is a fungus causing damaging disease on Cucurbitaceae plants. In this paper, we characterize a novel peroxisome biogenesis gene from this pathogen called FAM1. Although no genes with significant homology are present in Saccharomyces cerevisiae, FAM1 contains a predicted Pex4-binding site typical of Pex22 proteins, which function in the recycling of PTS receptors from peroxisomes to the cytosol. We show that FAM1 complements the defect in peroxisomal matrix protein import of S. cerevisiae pex22 mutants and that fam1 mutants are completely defective in peroxisome function, fatty acid metabolism, and pathogenicity. Remarkably, we found that this novel peroxin is specifically localized on the bounding membrane of Woronin bodies, which are small peroxisome-derived organelles unique to filamentous ascomycete fungi that function in septal pore plugging. Our finding suggests that these fungi have coopted the Woronin body for localized receptor recycling during matrix protein import. PMID- 26374122 TI - The Human Skin Microbiome Associates with the Outcome of and Is Influenced by Bacterial Infection. AB - The influence of the skin microbiota on host susceptibility to infectious agents is largely unexplored. The skin harbors diverse bacterial species that may promote or antagonize the growth of an invading pathogen. We developed a human infection model for Haemophilus ducreyi in which human volunteers are inoculated on the upper arm. After inoculation, papules form and either spontaneously resolve or progress to pustules. To examine the role of the skin microbiota in the outcome of H. ducreyi infection, we analyzed the microbiomes of four dose matched pairs of "resolvers" and "pustule formers" whose inoculation sites were swabbed at multiple time points. Bacteria present on the skin were identified by amplification and pyrosequencing of 16S rRNA genes. Nonmetric multidimensional scaling (NMDS) using Bray-Curtis dissimilarity between the preinfection microbiomes of infected sites showed that sites from the same volunteer clustered together and that pustule formers segregated from resolvers (P = 0.001, permutational multivariate analysis of variance [PERMANOVA]), suggesting that the preinfection microbiomes were associated with outcome. NMDS using Bray-Curtis dissimilarity of the endpoint samples showed that the pustule sites clustered together and were significantly different than the resolved sites (P = 0.001, PERMANOVA), suggesting that the microbiomes at the endpoint differed between the two groups. In addition to H. ducreyi, pustule-forming sites had a greater abundance of Proteobacteria, Bacteroidetes, Micrococcus, Corynebacterium, Paracoccus, and Staphylococcus species, whereas resolved sites had higher levels of Actinobacteria and Propionibacterium species. These results suggest that at baseline, resolvers and pustule formers have distinct skin bacterial communities which change in response to infection and the resultant immune response. IMPORTANCE: Human skin is home to a diverse community of microorganisms, collectively known as the skin microbiome. Some resident bacteria are thought to protect the skin from infection by outcompeting pathogens for resources or by priming the immune system's response to invaders. However, the influence of the skin microbiome on the susceptibility to or protection from infection has not been prospectively evaluated in humans. We characterized the skin microbiome before, during, and after experimental inoculation of the arm with Haemophilus ducreyi in matched volunteers who subsequently resolved the infection or formed abscesses. Our results suggest that the preinfection microbiomes of pustule formers and resolvers have distinct community structures which change in response to the progression of H. ducreyi infection to abscess formation. PMID- 26374123 TI - Defining New Therapeutics Using a More Immunocompetent Mouse Model of Antibody Enhanced Dengue Virus Infection. AB - With over 3.5 billion people at risk and approximately 390 million human infections per year, dengue virus (DENV) disease strains health care resources worldwide. Previously, we and others established models for DENV pathogenesis in mice that completely lack subunits of the receptors (Ifnar and Ifngr) for type I and type II interferon (IFN) signaling; however, the utility of these models is limited by the pleotropic effect of these cytokines on innate and adaptive immune system development and function. Here, we demonstrate that the specific deletion of Ifnar expression on subsets of murine myeloid cells (LysM Cre(+) Ifnar(flox/flox) [denoted as Ifnar(f/f) herein]) resulted in enhanced DENV replication in vivo. The administration of subneutralizing amounts of cross reactive anti-DENV monoclonal antibodies to LysM Cre(+) Ifnar(f/f) mice prior to infection with DENV serotype 2 or 3 resulted in antibody-dependent enhancement (ADE) of infection with many of the characteristics associated with severe DENV disease in humans, including plasma leakage, hypercytokinemia, liver injury, hemoconcentration, and thrombocytopenia. Notably, the pathogenesis of severe DENV 2 or DENV-3 infection in LysM Cre(+) Ifnar(f/f) mice was blocked by pre- or postexposure administration of a bispecific dual-affinity retargeting molecule (DART) or an optimized RIG-I receptor agonist that stimulates innate immune responses. Our findings establish a more immunocompetent animal model of ADE of infection with multiple DENV serotypes in which disease is inhibited by treatment with broad-spectrum antibody derivatives or innate immune stimulatory agents. IMPORTANCE: Although dengue virus (DENV) infects hundreds of millions of people annually and results in morbidity and mortality on a global scale, there are no approved antiviral treatments or vaccines. Part of the difficulty in evaluating therapeutic candidates is the lack of small animal models that are permissive to DENV and recapitulate the clinical features of severe human disease. Using animals lacking the type I interferon receptor only on myeloid cell subsets, we developed a more immunocompetent mouse model of severe DENV infection with characteristics of the human disease, including vascular leakage, hemoconcentration, thrombocytopenia, and liver injury. Using this model, we demonstrate that pathogenesis by two different DENV serotypes is inhibited by therapeutic administration of a genetically modified antibody or a RIG-I receptor agonist that stimulates innate immunity. PMID- 26374124 TI - Infection Dynamics and Immune Response in a Newly Described Drosophila Trypanosomatid Association. AB - Trypanosomatid parasites are significant causes of human disease and are ubiquitous in insects. Despite the importance of Drosophila melanogaster as a model of infection and immunity and a long awareness that trypanosomatid infection is common in the genus, no trypanosomatid parasites naturally infecting Drosophila have been characterized. Here, we establish a new model of trypanosomatid infection in Drosophila--Jaenimonas drosophilae, gen. et sp. nov. As far as we are aware, this is the first Drosophila-parasitic trypanosomatid to be cultured and characterized. Through experimental infections, we find that Drosophila falleni, the natural host, is highly susceptible to infection, leading to a substantial decrease in host fecundity. J. drosophilae has a broad host range, readily infecting a number of Drosophila species, including D. melanogaster, with oral infection of D. melanogaster larvae resulting in the induction of numerous immune genes. When injected into adult hemolymph, J. drosophilae kills D. melanogaster, although interestingly, neither the Imd nor the Toll pathway is induced and Imd mutants do not show increased susceptibility to infection. In contrast, mutants deficient in drosocrystallin, a major component of the peritrophic matrix, are more severely infected during oral infection, suggesting that the peritrophic matrix plays an important role in mediating trypanosomatid infection in Drosophila. This work demonstrates that the J. drosophilae-Drosophila system can be a powerful model to uncover the effects of trypanosomatids in their insect hosts. IMPORTANCE: Trypanosomatid parasites are ubiquitous in insects and are significant causes of disease when vectored to humans by blood-feeding insects. In recent decades, Drosophila has emerged as the predominant insect model of infection and immunity and is also known to be infected by trypanosomatids at high rates in the wild. Despite this, there has been almost no work on their trypanosomatid parasites, in part because Drosophila specific trypanosomatids have been resistant to culturing. Here, we present the first isolation and detailed characterization of a trypanosomatid from Drosophila, finding that it represents a new genus and species, Jaenimonas drosophilae. Using this parasite, we conducted a series of experiments that revealed many of the unknown aspects of trypanosomatid infection in Drosophila, including host range, transmission biology, dynamics of infection, and host immune response. Taken together, this work establishes J. drosophilae as a powerful new opportunity to study trypanosomatid infections in insects. PMID- 26374125 TI - Insights into Substrate Specificity of NlpC/P60 Cell Wall Hydrolases Containing Bacterial SH3 Domains. AB - Bacterial SH3 (SH3b) domains are commonly fused with papain-like Nlp/P60 cell wall hydrolase domains. To understand how the modular architecture of SH3b and NlpC/P60 affects the activity of the catalytic domain, three putative NlpC/P60 cell wall hydrolases were biochemically and structurally characterized. These enzymes all have gamma-d-Glu-A2pm (A2pm is diaminopimelic acid) cysteine amidase (or dl-endopeptidase) activities but with different substrate specificities. One enzyme is a cell wall lysin that cleaves peptidoglycan (PG), while the other two are cell wall recycling enzymes that only cleave stem peptides with an N-terminal l-Ala. Their crystal structures revealed a highly conserved structure consisting of two SH3b domains and a C-terminal NlpC/P60 catalytic domain, despite very low sequence identity. Interestingly, loops from the first SH3b domain dock into the ends of the active site groove of the catalytic domain, remodel the substrate binding site, and modulate substrate specificity. Two amino acid differences at the domain interface alter the substrate binding specificity in favor of stem peptides in recycling enzymes, whereas the SH3b domain may extend the peptidoglycan binding surface in the cell wall lysins. Remarkably, the cell wall lysin can be converted into a recycling enzyme with a single mutation. IMPORTANCE: Peptidoglycan is a meshlike polymer that envelops the bacterial plasma membrane and bestows structural integrity. Cell wall lysins and recycling enzymes are part of a set of lytic enzymes that target covalent bonds connecting the amino acid and amino sugar building blocks of the PG network. These hydrolases are involved in processes such as cell growth and division, autolysis, invasion, and PG turnover and recycling. To avoid cleavage of unintended substrates, these enzymes have very selective substrate specificities. Our biochemical and structural analysis of three modular NlpC/P60 hydrolases, one lysin, and two recycling enzymes, show that they may have evolved from a common molecular architecture, where the substrate preference is modulated by local changes. These results also suggest that new pathways for recycling PG turnover products, such as tracheal cytotoxin, may have evolved in bacteria in the human gut microbiome that involve NlpC/P60 cell wall hydrolases. PMID- 26374127 TI - Regions of the bread wheat D genome associated with variation in key photosynthesis traits and shoot biomass under both well watered and water deficient conditions. AB - A quantitative trait locus (QTL) approach was taken to reveal the genetic basis in wheat of traits associated with photosynthesis during a period of exposure to water deficit stress. The performance, with respect to shoot biomass, gas exchange and chlorophyll fluorescence, leaf pigment content and the activity of various ascorbate-glutathione cycle enzymes and catalase, of a set of 80 wheat lines, each containing a single chromosomal segment introgressed from the bread wheat D genome progenitor Aegilops tauschii, was monitored in plants exposed to various water regimes. Four of the seven D genome chromosomes (1D, 2D, 5D, and 7D) carried clusters of both major (LOD >3.0) and minor (LOD between 2.0 and 3.0) QTL. A major QTL underlying the activity of glutathione reductase was located on chromosome 2D, and another, controlling the activity of ascorbate peroxidase, on chromosome 7D. A region of chromosome 2D defined by the microsatellite locus Xgwm539 and a second on chromosome 7D flanked by the marker loci Xgwm1242 and Xgwm44 harbored a number of QTL associated with the water deficit stress response. PMID- 26374128 TI - Opioid dependency rehabilitation with the opioid maintenance treatment programme a qualitative study from the clients' perspective. AB - BACKGROUND: Opioid maintenance treatment (OMT) is the most widely used treatment for opioid dependence. The opioid maintenance treatment (OMT) programme represents an opportunity for people who are opioid users to minimize the many negative health and societal outcomes associated with opioid use through meeting the physiological need of their bodies for opioids. The purpose of this study is to shed some light on how clients in the Norwegian OMT programme see their level of influence on their own treatment. METHOD: It is a qualitative enquiry using semi-structured interviews of seven OMT clients living in various locations in Norway. The analysis of the material utilized a grounded theory-inspired approach. RESULTS: This study show that the clients who were part of the OMT programme had better lives than people with untreated addictions did. However, the participants experienced having to play by the rules of the OMT programme if they wanted to have successful treatment. This resulted in varying degrees of dissatisfaction with the treatment. CONCLUSIONS: The results indicated that the clients felt objectified and disenfranchised in the OMT programme, and points out the low level of influence on their own treatment felt by the OMT clients. PMID- 26374130 TI - The C175R mutation alters nuclear localization and transcriptional activity of the nephronophthisis NPHP7 gene product. AB - Nephronophthisis (NPH) is a rare autosomal ciliopathy, but the leading cause for hereditary end-stage renal disease in children. Most NPH family members form large protein networks, which appear to participate in structural elements of the cilium and/or function to restrict access of molecules to the ciliary compartment. The zinc-finger protein GLIS2/NPHP7 represents an exception as it has been implicated in transcriptional regulation; only two families with GLIS2/NPHP7 mutations and typical NPH manifestations have been identified so far. We describe here that the recently identified GLIS2/NPHP7(C175R) point mutation abolished the nuclear localization of GLIS2/NPHP7. Forced nuclear import did not rescue the transcriptional defects of GLIS2/NPHP7(C175R), indicating additional defects as DNA-binding protein. We further observed that wild type, but not GLIS2/NPHP7(C175R), prevented the cyst formation caused by depletion of nphp7 in zebrafish embryos. Taken together, our findings indicate that the C175R mutation affects both localization and function of GLIS2/NPHP7, supporting a role of this mutation in NPH, but questioning the direct involvement of GLIS2/NPHP7 in ciliary functions. PMID- 26374129 TI - Quantitative in vivo fusion assessment by (18)F-fluoride PET/CT following en bloc spondylectomy. AB - PURPOSE: The purpose of this retrospective analyses was to evaluate the bone viability in the ventral column of the spine following large segmental defect reconstructions. Osseous integration of implants following spinal fusion procedures is an essential precondition to provide adequate mechanical strength to any applied forces and subsequently satisfying patient outcomes. Although CT scan is the non-invasive gold standard for fusion assessment, it lacks the ability to visualize bone viability and, therefore, discrepancy remains about sensitivity and specificity of CT as evaluation tool of spinal fusion. METHODS: A novel modality, (18)F Fluoride PET/CT, specifically allows quantitative in vivo evaluation of metabolic activity of the osseous integration. Bone viability following large segmental reconstructions in patients after mono- and multi-level en bloc spondylectomies (EBS) was analyzed. Spinal fusion was assessed on plain radiographs and CT scans according to the FDA fusion criteria as well as (18)F PET/CT. RESULTS: A total of eight patients underwent (18)F PET/CT were included (one 4-level-, one 3-level, two 2-level and four 1-level EBS). The average follow up between EBS and radiographic studies was 24.8 months. On plain radiographs and CT scans, successful fusion was confirmed in all patients. However, (18)F PET/CT showed non-union in all cases. The metabolic bone activity within the cage was fourfold decreased compared to the reference vertebra, whereas the metabolic activity of the adjacent endplates was 1.6-fold increased compared to the reference vertebra. CONCLUSION: This study suggests a discrepancy between fusion rates assessed by plain radiographs and CT scan compared to (18)F PET/CT. PMID- 26374131 TI - Hereditary spastic paraplegia in Greece: characterisation of a previously unexplored population using next-generation sequencing. AB - Hereditary Spastic Paraplegia (HSP) is a syndrome characterised by lower limb spasticity, occurring alone or in association with other neurological manifestations, such as cognitive impairment, seizures, ataxia or neuropathy. HSP occurs worldwide, with different populations having different frequencies of causative genes. The Greek population has not yet been characterised. The purpose of this study was to describe the clinical presentation and molecular epidemiology of the largest cohort of HSP in Greece, comprising 54 patients from 40 families. We used a targeted next-generation sequencing (NGS) approach to genetically assess a proband from each family. We made a genetic diagnosis in >50% of cases and identified 11 novel variants. Variants in SPAST and KIF5A were the most common causes of autosomal dominant HSP, whereas SPG11 and CYP7B1 were the most common cause of autosomal recessive HSP. We identified a novel variant in SPG11, which led to disease with later onset and may be unique to the Greek population and report the first nonsense mutation in KIF5A. Interestingly, the frequency of HSP mutations in the Greek population, which is relatively isolated, was very similar to other European populations. We confirm that NGS approaches are an efficient diagnostic tool and should be employed early in the assessment of HSP patients. PMID- 26374133 TI - Easily processable multimodal spectral converters based on metal oxide/organic inorganic hybrid nanocomposites. AB - This manuscript reports the synthesis and characterization of the first organic inorganic hybrid material exhibiting efficient multimodal spectral converting properties. The nanocomposite, made of Er(3+), Yb(3+) codoped zirconia nanoparticles (NPs) entrapped in a di-ureasil d-U(600) hybrid matrix, is prepared by an easy two-step sol-gel synthesis leading to homogeneous and transparent materials that can be very easily processed as monolith or film. Extensive structural characterization reveals that zirconia nanocrystals of 10-20 nm in size are efficiently dispersed into the hybrid matrix and that the local structure of the di-ureasil is not affected by the presence of the NPs. A significant enhancement in the refractive index of the di-ureasil matrix with the incorporation of the ZrO2 nanocrystals is observed. The optical study demonstrates that luminescent properties of both constituents are perfectly preserved in the final hybrid. Thus, the material displays a white-light photoluminescence from the di-ureasil component upon excitation at UV/visible radiation and also intense green and red emissions from the Er(3+)- and Yb(3+) doped NPs after NIR excitation. The dynamics of the optical processes were also studied as a function of the lanthanide content and the thickness of the films. Our results indicate that these luminescent hybrids represent a low-cost, environmentally friendly, size-controlled, easily processed and chemically stable alternative material to be used in light harvesting devices such as luminescent solar concentrators, optical fibres and sensors. Furthermore, this synthetic approach can be extended to a wide variety of luminescent NPs entrapped in hybrid matrices, thus leading to multifunctional and versatile materials for efficient tuneable nonlinear optical nanodevices. PMID- 26374132 TI - Origins, admixture and founder lineages in European Roma. AB - The Roma, also known as 'Gypsies', represent the largest and the most widespread ethnic minority of Europe. There is increasing evidence, based on linguistic, anthropological and genetic data, to suggest that they originated from the Indian subcontinent, with subsequent bottlenecks and undetermined gene flow from/to hosting populations during their diaspora. Further support comes from the presence of Indian uniparentally inherited lineages, such as mitochondrial DNA M and Y-chromosome H haplogroups, in a significant number of Roma individuals. However, the limited resolution of most genetic studies so far, together with the restriction of the samples used, have prevented the detection of other non-Indian founder lineages that might have been present in the proto-Roma population. We performed a high-resolution study of the uniparental genomes of 753 Roma and 984 non-Roma hosting European individuals. Roma groups show lower genetic diversity and high heterogeneity compared with non-Roma samples as a result of lower effective population size and extensive drift, consistent with a series of bottlenecks during their diaspora. We found a set of founder lineages, present in the Roma and virtually absent in the non-Roma, for the maternal (H7, J1b3, J1c1, M18, M35b, M5a1, U3, and X2d) and paternal (I-P259, J-M92, and J-M67) genomes. This lineage classification allows us to identify extensive gene flow from non Roma to Roma groups, whereas the opposite pattern, although not negligible, is substantially lower (up to 6.3%). Finally, the exact haplotype matching analysis of both uniparental lineages consistently points to a Northwestern origin of the proto-Roma population within the Indian subcontinent. PMID- 26374134 TI - Selective serotonin reuptake inhibitors and childhood motor skill impairment-what can be concluded? PMID- 26374135 TI - A Cross-Sectional Descriptive Study of Occupational Therapy Students' Perceptions and Attitudes Towards Spirituality and Spiritual Care in Occupational Therapy Education. AB - Spirituality and spiritual care both have received increased attention over the course of this past decade from different disciplines. However, for many years, in the occupational therapy profession, the importance of spirituality and spiritual care seems to be controversial because it is unclear how these concepts are integrated in occupational therapy education. Although occupational therapy students are being educated to consider a holistic and client-centred approach, spirituality is not regarded within this framework which diminishes the integrity of holistic approach. In South African occupational therapy education, it is unclear whether any single course on teaching and learning of spirituality and spiritual care exists. Thus, the aim of this study was to describe occupational therapy students' perceptions and attitudes regarding spirituality and spiritual care in occupational therapy education. A cross-sectional descriptive study design of undergraduate occupational therapy students from one educational institution was used. Data included demographic characteristics, responses on Spiritual Care-Giving Scale (SCGS), Spiritual and Spiritual Care Rating Scale (SSCRS) and Spirituality in Occupational Therapy Scale (SOTS). A response rate of 50.5 % (n = 100 out of 198) was achieved. In the SCGS, among the factors only factor 1 had the highest mean value score showing consistent agreement about spirituality, whereas in the SSCRS only three factors were found to have highest mean score and one with lowest mean score. In SOTS, participants had a highest score mean in relation to formal education and training about spirituality. Thus, in the integration of spirituality and spiritual care a holistic approach needs to be considered in education to enhance students' knowledge of how to address mind, body and spirit needs. PMID- 26374136 TI - Trashing epidemiology and public health with bibliometry? In defence of science in Germany (and elsewhere). PMID- 26374137 TI - Post-embolization syndrome as an early predictor of overall survival after transarterial chemoembolization for hepatocellular carcinoma. AB - BACKGROUND: Transarterial chemoembolization (TACE) is the most common treatment for patients with unresectable hepatocellular carcinoma (HCC). Post-embolization syndrome (PES) is a common post-TACE complication. The goal of this study was to evaluate PES as an early predictor of the long-term outcome. METHODS: A retrospective cohort study of HCC patients treated with TACE at a tertiary referral centre was performed (2008-2014). Patients were categorized on the basis of PES, defined as fever with or without abdominal pain within 14 days of TACE. The primary outcome was overall survival (OS). Multivariate Cox regression was done to examine the association between PES and OS. RESULTS: Among 144 patients, 52 (36.1%) experienced PES. The median follow-up for the cohort was 11.4 months. The median and 3-year OS rates were 16 months and 18% in the PES group versus 25 months and 41% in the non-PES group (log rank, P = 0.027). After multivariate analysis, patients with PES had a significantly increased risk of death [hazard ratio 2.0 (95%CI 1.2-3.3), P = 0.011]. CONCLUSIONS: PES is a common complication after TACE and is associated with a two-fold increased risk of death. Future studies should incorporate PES as a relevant early predictor of OS and examine the biological basis of this association. PMID- 26374138 TI - Longer Immediate Recovery Time After Anesthesia Increases Risk of Respiratory Complications After Laparotomy for Bariatric Surgery: a Randomized Clinical Trial and a Cohort Study. AB - BACKGROUND: We compared the effects of two anesthesia protocols in both immediate recovery time (IRT) and postoperative respiratory complications (PRCs) after laparotomy for bariatric surgery, and we determined the association between the longer IRT and the increase of PRC incidence. METHODS: We conducted the study in two stages: (i) in a randomized controlled trial (RCT), patients received either intervention (sevoflurane-remifentanil-rocuronium-ropivacaine) or control protocol (isoflurane-sufentanil-atracurium-levobupivacaine). All patients received general anesthesia plus continuous epidural anesthesia and analgesia. Treatment was masked for all, except the provider anesthesiologist. We defined IRT as time since anesthetics discontinuation until tracheal extubation. Primary outcomes were IRT and PRCs incidence within 15 days after surgery. We also analyzed post-anesthesia care unit (PACU) and hospital length of stays; (ii) after the end of the RCT, we used the available data in an extension cohort study to investigate IRT > 20 min as exposure factor for PRCs. RESULTS: Control protocol (n = 152) resulted in longer IRT (30.4 +/- 7.9 vs 18.2 +/- 9.6 min; p < 0.0001), higher incidence of PRCs (6.58 vs 2.5 %; p = 0.048), and longer PACU and hospital stays than intervention protocol (n = 200); PRC relative risk (RR) = 2.6. Patients with IRT > 20 min (n = 190) presented higher incidence of PRCs (7.37 vs 0.62 %; p < 0.0001); RR = 12.06. CONCLUSIONS: Intervention protocol, with short-acting anesthetics, was more beneficial and safe compared to control protocol, with long-acting drugs, regarding the reduction of IRT, PRCs, and PACU and hospital stays for laparotomy in bariatric patients. We identified a 4.5-fold increase in the relative risk of PRCs when morbid obese patients are exposed to an IRT > 20 min. PMID- 26374139 TI - Patients in transition--improving hospital-home care collaboration through electronic messaging: providers' perspectives. AB - AIMS AND OBJECTIVES: To explore how the use of electronic messages support hospital and community care nurses' collaboration and communication concerning patients' admittance to and discharges from hospitals. BACKGROUND: Nurses in hospitals and in community care play a crucial role in the transfer of patients between the home and the hospital. Several studies have shown that transition situations are challenging due to a lack of communication and information exchange. Information and communication technologies may support nurses' work in these transition situations. An electronic message system was introduced in Norway to support patient transitions across the health care sector. DESIGN: A descriptive, qualitative interview study was conducted. METHODS: One hospital and three adjacent communities were included in the study. We conducted semi structured interviews with hospital nurses and community care nurses. In total, 41 persons were included in the study. The analysis stemmed from three main topics related to the aims of e-messaging: efficiency, quality and safety. These were further divided into sub-themes. RESULTS: All informants agreed that electronic messaging is more efficient, i.e. less time-consuming than previous means of communication. The shift from predominantly oral communication to writing electronic messages has brought attention to the content of the information exchanged, thereby leading to more conscious communication. Electronic messaging enables improved information security, thereby enhancing patient safety, but this depends on nurses using the system as intended. CONCLUSION: Nurses consider electronic messaging to be a useful tool for communication and collaboration in patient transitions. RELEVANCE TO CLINICAL PRACTICE: Patient transitions are demanding situations both for patients and for the nurses who facilitate the transitions. The introduction of information and communication technologies can support nurses' work in the transition situations, and this is likely to benefit the patients. PMID- 26374140 TI - Healthy Aging 5 Years After a Period of Daily Supplementation With Antioxidant Nutrients: A Post Hoc Analysis of the French Randomized Trial SU.VI.MAX. AB - This study's objective was to investigate healthy aging in older French adults 5 years after a period of daily nutritional-dose supplementation with antioxidant nutrients. The study was based on the double-blind, randomized trial, Supplementation with Antioxidant Vitamins and Minerals (SU.VI.MAX) Study (1994 2002) and the SU.VI.MAX 2 Follow-up Study (2007-2009). During 1994-2002, participants received a daily combination of vitamin C (120 mg), beta-carotene (6 mg), vitamin E (30 mg), selenium (100 ug), and zinc (20 mg) or placebo. Healthy aging was assessed in 2007-2009 by using multiple criteria, including the absence of major chronic disease and good physical and cognitive functioning. Data from a subsample of the SU.VI.MAX 2 cohort, initially free of major chronic disease, with a mean age of 65.3 years in 2007-2009 (n = 3,966), were used to calculate relative risks. Supplementation was associated with a greater healthy aging probability among men (relative risk = 1.16, 95% confidence interval: 1.04, 1.29) but not among women (relative risk = 0.98, 95% confidence interval: 0.86, 1.11) or all participants (relative risk = 1.07, 95% confidence interval: 0.99, 1.16). Moreover, exploratory subgroup analyses indicated effect modification by initial serum concentrations of zinc and vitamin C. In conclusion, an adequate supply of antioxidant nutrients (equivalent to quantities provided by a balanced diet rich in fruits and vegetables) may have a beneficial role for healthy aging. PMID- 26374141 TI - Rhodanobacter aciditrophus sp. nov., an acidophilic bacterium isolated from mine wastewater. AB - A novel strain (designated sjH1T), characterized as aerobic, Gram-stain-negative, oxidase-positive, catalase-negative, motile and rod-shaped, was isolated from mine wastewater. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain sjH1T belonged to the genus Rhodanobacter. Strain sjH1T was closely related to Rhodanobacter thiooxydans LCS2T (98.0% 16S rRNA gene sequence similarity), Rhodanobacter denitrificans 2APBS1T (97.7%), Rhodanobacter soli DCY45T (97.2%) and Rhodanobacter caeni MJ01T (97.0%). The DNA G+C content of strain sjH1T was 69.2 mol%. DNA-DNA relatedness ( < 60%) indicated that strain sjH1T represents a distinct species that is separate from R. thiooxydans, R. denitrificans, R. soli and R. caeni. The major ubiquinone was Q-8, and major fatty acids were summed feature 9 (iso-C17 : 1omega9c and/or C16 : 0 10-methyl), iso-C15 : 0, iso-C17 : 0, iso-C16 : 0 and anteiso-C15 : 0. Based on data from this polyphasic study, it is proposed that sjH1T ( = KCTC 42660T = JCM 30774T) is the type strain of a novel species, Rhodanobacter aciditrophus sp. nov. PMID- 26374142 TI - Transition metal complexes bearing NHC ligands substituted with secondary polyfluoroalkyl groups. AB - Using three different approaches, racemic 1-(perfluoroalkyl)ethylamines were synthesized from perfluoroalkyl iodides or perfluoroalkanoic acids, and further transformed to the corresponding N,N'-disubstituted ethane-1,2-diimines and ethane-1,2-diamines as mixtures of diastereoisomers. Their cyclization afforded imidazolium or dihydroimidazolium salts, which led to silver or palladium complexes bearing NHC ligands substituted with secondary polyfluoroalkyl groups. The palladium complexes bearing a throwaway 3-chloropyridine ligand proved to be moderately active in the model Suzuki-Miyaura coupling. PMID- 26374143 TI - Comparison of Efficacy and Cost of Iodine Impregnated Drape vs. Standard Drape in Cardiac Surgery: Study in 5100 Patients. AB - We sought to examine the efficacy in preventing surgical site infection (SSI) in cardiac surgery, using two different incise drapes (not iodine-impregnated and iodine-impregnated). A cost analysis was also considered. Between January 2008 and March 2015, 5100 consecutive cardiac surgery patients, who underwent surgery in our Institute, were prospectively collected. A total of 3320 patients received a standard not iodine-impregnated steri-drape (group A), and 1780 patients received Ioban((r)) 2 drape (group B). We investigated, by a propensity matched analysis, whether the use of standard incise drape or iodine-impregnated drape would impact upon SSI rate. Totally, 808 patients for each group were matched for the available risk factors. Overall incidence of SSI was significantly higher in group A (6.5 versus 1.9 %) (p = 0.001). Superficial SSI incidence was significantly higher in group A (5.1 vs 1.6 %) (p = 0.002). Deep SSI resulted higher in group A (1.4 %) than in group B (0.4 %), although not significantly (p = 0.11). Consequently, the need for vacuum-assisted closure (VAC) therapy use resulted 4.3 % in group A versus 1.2 % in group B (p = 0.001). Overall costs for groups A and B were 12.494.912 ? and 11.721.417 ?, respectively. The Ioban((r)) 2 offered totally 773.495 ? cost savings compared to standard steri-drape. Ioban 2 drape assured a significantly lower incidence of SSI. Additionally, Ioban((r)) 2 drape proved to be cost-effective in cardiac surgery. PMID- 26374145 TI - Is hepcidin-25 a predictor of atherosclerosis in hemodialysis patients? AB - Atherosclerotic cardiovascular disease is an important cause of mortality and morbidity in hemodialysis patients. Iron accumulation in arterial wall macrophages is increased in atherosclerotic lesions. Hepcidin is a key hepatic hormone regulating iron balance. It inhibits iron release from macrophages and iron absorption from enterocytes by binding and inactivating the cellular iron exporter ferroportin. The aim of this study is to investigate the relation of hepcidin-25, iron parameters, and atherosclerosis measured by carotid intima media thickness (CIMT) in hemodialysis patients. Eighty-two hemodialysis patients were enrolled in this cross-sectional study. Predialysis blood samples were centrifuged at 1500 g and 4 degrees C for 10 minutes and stored at -80 degrees C for the measurement of hepcidin-25. DRG hepcidin enzyme-linked immunosorbent assay kit was used for the measurement of hepcidin-25. Ultrasonographical B-mode imaging of bilateral carotid arteries was performed with a high-resolution real time ultrasonography (Mindray DC7). Mean age of the study population was 57.90 +/ 16.08 years and 43.9% were men. Total study population was grouped into two according to median value of hepcidin-25. There was no difference between groups with respect to age, dialysis vintage, and C-reactive protein. CIMT was found to be statistically significantly higher in low hepcidin-25 group. In correlation analysis, CIMT was found to be correlated with age (P < 0.01, R = 0.33) and hepcidin-25 (P < 0.01, R = 0.46). In linear regression analysis, age (beta = 0.31) and hepcidin-25 (beta = 0.44) were found to be the determinants of CIMT in hemodialysis patients. Our results implicate that hepcidin may take part in pathophysiology of atherosclerosis and cardiovascular disease in hemodialysis patients. PMID- 26374146 TI - German drug companies are criticised for not focusing on useful therapeutic areas. PMID- 26374144 TI - Intravenous Followed by X-ray Fused with MRI-Guided Transendocardial Mesenchymal Stem Cell Injection Improves Contractility Reserve in a Swine Model of Myocardial Infarction. AB - The aim of this study is to determine the effects of early intravenous (IV) infusion later followed by transendocardial (TE) injection of allogeneic mesenchymal stem cells (MSCs) following myocardial infarction (MI). Twenty-four swine underwent balloon occlusion reperfusion MI and were randomized into 4 groups: IV MSC (or placebo) infusion (post-MI day 2) and TE MSC (or placebo) injection targeting the infarct border with 2D X-ray fluoroscopy fused to 3D magnetic resonance (XFM) co-registration (post-MI day 14). Continuous ECG recording, MRI, and invasive pressure-volume analyses were performed. IV MSC plus TE MSC treated group was superior to other groups for contractility reserve (p = 0.02) and freedom from VT (p = 0.03) but had more lymphocytic foci localized to the peri-infarct region (p = 0.002). No differences were observed in post-MI remodeling parameters. IV followed by XFM targeted TE MSC therapy improves contractility reserve and suppresses VT but does not affect post-MI remodeling and may cause an immune response. PMID- 26374147 TI - Beating the amorphous limit in thermal conductivity by superlattices design. AB - The value measured in the amorphous structure with the same chemical composition is often considered as a lower bound for the thermal conductivity of any material: the heat carriers are strongly scattered by disorder, and their lifetimes reach the minimum time scale of thermal vibrations. An appropriate design at the nano-scale, however, may allow one to reduce the thermal conductivity even below the amorphous limit. In the present contribution, using molecular-dynamics simulation and the Green-Kubo formulation, we study systematically the thermal conductivity of layered phononic materials (superlattices), by tuning different parameters that can characterize such structures. We have discovered that the key to reach a lower-than-amorphous thermal conductivity is to block almost completely the propagation of the heat carriers, the superlattice phonons. We demonstrate that a large mass difference in the two intercalated layers, or weakened interactions across the interface between layers result in materials with very low thermal conductivity, below the values of the corresponding amorphous counterparts. PMID- 26374150 TI - Detection of leukemia markers using long-range surface plasmon waveguides functionalized with Protein G. AB - A novel optical biosensor based on long-range surface plasmon-polariton (LRSPP) waveguides is demonstrated for the detection of leukemia markers in patient serum using a functionalization strategy based on Protein G. The sensor consists of thin straight Au waveguides (5 MUm * 35 nm * 3.2 mm) embedded in fluoropolymer CYTOPTM with a fluidic channel etched into the top cladding. B-cell leukemia is characterized by a high B-cell count and abnormal distribution of immunoglobulin G kappa (IgGkappa) and lambda (IgGlambda) light chains in serum. The detection of leukemic abnormalities in serum was performed based on determining IgGkappa-to IgGlambda ratios (kappa : lambda). Three patient sera were tested: high kappa (HKS, kappa : lambda ~12.7 : 1), high lambda (HLS, lambda : kappa ~6.9 : 1) and normal (control) sera (NS, kappa : lambda ~1.7 : 1). Au waveguides were functionalized with Protein G and two complementary immobilization approaches were investigated: a) the reverse approach, where the Protein G surface is functionalized with patient serum and then tested against goat anti-human IgG light chains in buffer, and b) the direct approach, where the Protein G surface is functionalized with goat anti-human IgGs first and then tested against patient serum. The reverse approach was found to be more effective and robust because Protein G-functionalized surface performs as an "immunological filter" by capturing primarily IgGs out of the pool of serum proteins. For the reverse approach, the ratios measured were 3.7 : 1(kappa : lambda), 9.7 : 1(lambda : kappa) and 1.9 : 1(kappa : lambda) for HKS, HLS and NS, respectively, which compare favorably with corresponding protein densitometry measurements. The respective ratios for the direct approach were 2.6 : 1(kappa : lambda), 2.6 : 1(lambda : kappa) and 1.7 : 1(kappa : lambda). The binding strength and cross reactivity of goat anti-human IgGs light chains were also determined using pure solutions. The LRSPP biosensor along with the innovative "reverse approach" can provide a low-cost and compact solution to B-cell leukemia screening. PMID- 26374152 TI - [What Can Study of Oligomerization of Proteins in the Process of Oncogenesis Bring Us?]. AB - Many cellular proteins form oligomers. The equilibrium between monomeric and oligomeric states of these proteins is important for the regulation of protein activity. Modulation of the oligomerization equilibrium could be an interesting approach in the development of new therapeutic agents. This review summarizes information about protein oligomerization and modulation of this process, demonstrating the role of oligomerization in oncogenesis by tumor suppressor protein p53, which forms tetrameric structure. Today, many studies focus on finding compounds that stabilize its tetramers. Among the methods for studying oligomerization, we present hydrogen/ deuterium exchange method coupled with mass spectrometry which is suitable for the detection of protein-protein interaction and analysis of oligomerization dynamics. PMID- 26374153 TI - [Analysis of Phosphoproteome Changes in MDA MB 468 Cancer Cell Line in Response to Expression of p63 Isoforms Using Mass Spectrometry]. AB - Compared to normal cells, tumor cells can show different activity of kinases and phosphatases resulting in altered phosphorylation states of proteins affecting their activity within various signaling pathways. The detection of these alterations is essential for development of targeted therapy based on activation/ inhibition of specific signaling pathways. Various methods can be used for detection of protein phosphorylation; however, a comprehensive assessment of phosphoproteome is performed by mass spectrometry. The differences in phosphoproteome were studied using MDA MB 468 cell line (with incorporated genes encoding isoforms of p63) derived from breast carcinoma. Cells with tetracycline-induced expression of the p63 isoforms were compared to control cells with wildtype expression. Denatured proteins from cell lysates were digested to peptides, enriched for phosphopeptides and subsequently separated using liquid chromatograph coupled with mass spectrometer Orbitrap Elite. Three different mass spectrometric methods were used for each sample analysis to find the most suitable conditions for the detection of phosphorylated peptides. Then phosphoproteins were identified and quantified. The number of identified phosphoproteins using all chosen mass spectrometric methods was similar; however, each method showed several unique phosphorylated proteins. Our analysis revealed that both p63 isoforms (TAp63alpha a Np63alpha) mainly affected phosphorylation of proteins associated with RNA splicing in MDA- MB- 468 cells. PMID- 26374154 TI - [Sugars Interfere or Glycomics in the Field of Cancer Biomarkers]. AB - Glycomics is concerned with detection and characterization of glycans present in biological samples. It is well-known that glycan structures impart high degree of structural diversity to biomolecules and thus add wide -ranging biological functions, such as cellular recognition, adhesion or involvement in cellular signaling pathways. They substantially participate in oncogenesis, e. g. in phases of invasion, metastasis and angiogenesis. Therefore, analysis of glycan structures in tumor tissues or body liquids is a promising tool for searching for potential tumor biomarkers essential for an early diagnosis of the neoplastic disease. The presented review describes the process of glycosylation and the origination of N and O glycans, presenting examples of glycan profiling in pancreatic, prostate and ovarian cancer. PMID- 26374155 TI - [Nrf2--Two Faces of Antioxidant System Regulation]. AB - One of the most prominent defense mechanisms of cells undergoing stress is the Nrf2-Keap1 signaling pathway. After exposure to either carcinogens or toxic compounds inducing oxidative stress, attacked cells react by release of Keap1 from the Nrf2-Keap1 complex. Freeing Nrf2 from the complex allows its translocation into the nucleus, thus enabling start of the transcriptional program of cytoprotective genes. Therefore, induction of Nrf2 by chemopreventive compounds may show potential in cancer prevention. But while it protects normal cells, increased activity of Nrf2 signaling pathway also facilitates cancer progression and protects neoplastic cells from therapeutic agents. Increased expression and subsequent accumulation of Nrf2 contributes to acquired drug resistance and is often associated with worse prognosis. Knowing both faces of Nrf2 signaling pathway is thus relevant not only for basic research but has also substantial clinical implications. PMID- 26374156 TI - [Polo-like Kinase 1 as a Target for Anti-tumor Therapy]. AB - Individual proteins from polo-like kinase (Plk) family fulfil different but critical functions in regulating cell cycle and coordinate cell response to DNA damage. The most studied one from this five member family is Plk1. It is a serine/ threonine kinase that plays a pivotal role in many aspects of mitosis and its deregulation is common in various tumor types where the elevated level is mostly associated with worse prognosis. From the therapeutical point of view, intertwined relationship between Plk1 and p53 protein is very interesting and will be discussed. Not only for these reasons, Plk1 has become an attractive target for antitumor drug development. The most promising seems to be ATP binding site inhibitor Volasertib (BI 6727) which provided a survival benefit for patients with acute myeloid leukemia and is now tested in phase III clinical trial. A new generation of Plk1 inhibitors that target the second druggable domain of Plk1, the polo- box domain, is currently being tested preclinically and are believed to improve Plk1 specificity. PMID- 26374157 TI - [PDLIM2 and Its Role in Oncogenesis--Tumor Suppressor or Oncoprote?]. AB - PDZ and LIM domain containing protein 2 (PDLIM2), also known as Mystique or SLIM, is a member of the actinin-associated LIM family of proteins that play essential roles in cytoskeletone organization, cell differentiation and have been associated with oncogenesis. PDLIM2 is cytoskeletal and nuclear protein encoded by the Mystique gene localized on chromosome 8p21. PDLIM2 regulates stability and activity of several transcription factors, e. g. NF kappaB or STAT, and its deregulation is associated with several malignancies. PDLIM2 expression has been connected with both tumor suppression and tumorigenesis. PDLIM2 levels are epigenetically suppressed in different cancers due to Mystique promoter hypermetylation that blocks its transcription. PDLIM2 re expression is able to inhibit tumorigenicity and induces tumor cell death both in vitro and in vivo, which suggest potential tumor suppressor role of PDLIM2. On the other hand, PDLIM2 is highly expressed in cancer cell lines derived from metastatic cancer and its expression is associated with tumor progression and metastasis formation, indicating pro oncogenic role of PDLIM2. The aim of this review is to summarize current knowledge on the role of PDLIM2 in tumor formation and development, focusing on its prospective role as therapeutic target and offering potential explanations of its different functions in oncogenesis that were identified so far. PMID- 26374158 TI - [Profile of Activation of Tyrosine Kinases and MAP Kinases in Therapy of Maffucci Syndrome]. AB - BACKGROUND: Maffucci syndrome is a rare congenital nonhereditary disease characterized by multiple hemangiomas and enchondromas, which may progress into malignancy. The causal therapy does not exist, and therapy is aimed at complications. The determination of appropriate therapy is complicated, and a multidisciplinary approach is often essential. CASE: Authors are presenting the case of a 20-year -old patient with Maffucci syndrome. During her life, multiple enchondromas and progressing hemangiomas have been revealed and they have caused many complications, such as limited movement, growth failure, pain, fluidothorax and ascites. A profile of phosphorylation of selected tyrosine kinases and MAP kinases from progressing hemangioma was performed and with consideration of the result, it led to change of treatment strategy with encouraging clinical response lasting for six months. PMID- 26374159 TI - [Recombinant Antibodies and Their Employment in Cancer Therapy]. AB - Development of recombinant therapeutic antibodies is recently one of the fastest growing disciplines of applied biomedical research. Recombinant monoclonal antibodies are increasingly applied in biological therapy of many serious human diseases and are currently an irreplaceable part of a comprehensive cancer therapy. First mouse therapeutic antibodies had only limited applicability due to the strong immune response; however, technological advances enabled engineering of antibodies with increased specificity and efficacy, and on the other hand with reduced adverse effects due to lower antigenicity. This review provides a summary of knowledge about recombinant therapeutic antibodies, their mechanism of action and approaches how to improve their efficacy. PMID- 26374160 TI - [Immunological Aspects in Oncology--Circulating gammadelta T Cells]. AB - gammadelta T cells present a minor population of the T cell family which basically differs in construction of their T cell receptor (TCR). Thanks to the features of gammadelta TCR, these cells can acquire unique effector functions and play a specific role (not only) in antitumor immune response. In this article, we describe the basic characteristics of this cell population and their connection to cancer. In the experimental part we performed exploratory analysis of circulating gammadelta T cells in reference population and comparison with melanoma and breast carcinoma patients. The median percentage of gammadelta T cells from all lymphocytes was 2.9% (interquartile range-IQR 1.7-4%). The median absolute numbers of gammadelta cells per liter of blood was 5.05*10(7) (IQR 2.9 7.84*10(7)). The median percentage of gammadelta cells between all CD3 T cells was 3.9% (IQR 2.3-5.6%). No correlation between gammadelta T cells levels and gender or age was observed in reference population. Detailed immunophenotyping was also conducted describing representation of memory subsets (using CD45RO and CD27 markers) and presence of surface markers HLADr, CD69, CD25, CD28, CCR7, CTLA 4, ICOS, PD 1L and PD 1 between gammadelta T cells of the controls and breast carcinoma patients. From this analysis, it is evident that gammadelta T cells do not represent a uniform population but they differ in surface markers as well as in their effector functions. PMID- 26374161 TI - [Circulating Tumor DNA in Blood and Its Utilization as a Potential Biomarker for Cancer]. AB - Pursuing sensitive methods for detection and monitoring of oncologic diseases, that would limit the stress for patients, represents a longstanding challenge in cancer diagnostics. As an ideal noninvasive bio-markers may be considered bio logical molecules that can be detected in blood and that provide most relevant picture about the state and development of disease. In fact, all types of cancer cells carry somatic mutations that enable the cells to escape from regulation and to grow and progress. These mutations are only present in the DNA of tumor cells and thus are hallmarks of cancer cells. Genotyping of tumor tissues becomes a common technique in clinical oncology, but it has its limits. Tissue biopsy only yields information about a very small area of tumor at the time of extraction and in some cases it is difficult or impossible to obtain the tissue sample. Furthermore, it is an invasive method that can stress patients. Analysis of circulating tumor DNA from blood--the so-called liquid biopsy--represents one possible solution. Dying tumor cells release fragments of their DNA into the blood stream. From blood, they can be isolated and subjected to analysis using new, sensitive and precise methods that detect genomic changes. These changes are evolving over time because cancer disease is characterized by evolution and ability to select new mutations that bring growth advantages or resistance to treatment. Our inability to capture the heterogeneity during tumor development is one of the major reasons responsible for failure of cancer treatment. Recent technological progress in detection and characterization of circulating DNA could enable tumor evolution monitoring in real time and become a guideline for an accurate and prompt treatment choice. PMID- 26374162 TI - [Adenoviral Vectors in Gene Therapy]. AB - This review is focused on gene therapy, especially adenovirus vectors and their relationship with the immune system response. Adenovirus vectors belong to the most used gene delivery vehicles in gene therapy, study of gene expression or immunotherapy. One of the most important questions concerning their use is their influence on organism in vivo. Study of immunomodulating properties of the adenovirus vectors opens a way for further manipulation and their more effective practical use. PMID- 26374163 TI - [Cancer in Adolescents]. AB - Cancer in adolescents (15 to 19 years) appears to be a serious medical, psychologic, ethical and economical problem as well. This group of patients has been languishing in the shadow of pediatric oncology and out of interest of adult oncology. Spectrum of types of tumors and their biologal characteristics are age- specific and different from all other age groups. The overall incidence of cancer in adolescents is continuously increasing. Treatment results and outcome of adolescent cancer are worse compared with outcome in children with cancer younger than 15 years. PMID- 26374164 TI - [Bioinformatics and Next -generation Sequencing]. AB - Next-generation sequencing technologies are currently well-established in the research field and progressively find their way towards clinical applications. Sequencers produce vast amounts of data and therefore bioinformatics methods are needed for processing. Without computational methods, sequencing would not be able to produce relevant biological information. In this review, we introduce the basics of common NGS-related bioinformatics methods used in oncological research. We also state some of the common problems complicating data processing and interpretation of the results. PMID- 26374166 TI - A genome-wide association study reveals a quantitative trait locus for days open on chromosome 2 in Japanese Black cattle. AB - Days open (DO), which is the interval from calving to conception, is an important trait related to reproductive performance in cattle. To identify quantitative trait loci for DO in Japanese Black cattle, we conducted a genome-wide association study with 33,303 single nucleotide polymorphisms (SNPs) using 459 animals with extreme DO values selected from a larger group of 15,488 animals. We identified a SNP on bovine chromosome 2 (BTA2) that was associated with DO. After imputation using phased haplotype data inferred from 586 812 SNPs of 1041 Japanese Black cattle, six SNPs associated with DO were located in an 8.5-kb region of high linkage disequilibrium on BTA2. These SNPs were located on the telomeric side at a distance of 177 kb from the parathyroid hormone 2 receptor (PTH2R) gene. The association was replicated in a sample of 1778 animals. In the replicated population, the frequency of the reduced-DO allele (Q) was 0.63, and it accounted for 1.72% of the total genetic variance. The effect of a Q-to-q allele substitution on DO was a decrease of 3.74 days. The results suggest that the Q allele could serve as a marker in Japanese Black cattle to select animals with superior DO performance. PMID- 26374167 TI - Reactivity of an All-Ferrous Iron-Nitrogen Heterocubane under Reductive and Oxidative Conditions. AB - The reactivity of the all-ferrous FeN heterocubane [Fe4 (Ntrop)4 ] (1) with i) Bronsted acids, ii) sigma-donors, iii) sigma-donors/pi-acceptors, and iv) one electron oxidants has been investigated (trop = 5H-dibenzo[a,d]cyclo-hepten-5 yl). 1 showed self-re-assembling after reactions with i) and proved surprisingly inert in reactions with ii) and iii), with the exception of CO. Reductive and oxidative cluster degradation was observed in reactions with CO and TEMPO, respectively. These reactions yielded new cluster compounds, namely a trinuclear bis(MU3 -imido) 48 electron complex in the former case and a tetranuclear all ferric MU-oxo-MU-imido species in the latter case. Characterization techniques include NMR and in situ IR spectroscopy, single crystal X-ray analysis, Mossbauer spectroscopy, cyclic voltammetry, magnetic susceptibility measurements, and DFT calculations. PMID- 26374165 TI - Antagonistic effects of IL-17 and D-resolvins on endothelial Del-1 expression through a GSK-3beta-C/EBPbeta pathway. AB - Del-1 is an endothelial cell-secreted anti-inflammatory protein. In humans and mice, Del-1 expression is inversely related to that of IL-17, which inhibits Del 1 through hitherto unidentified mechanism(s). Here we show that IL-17 downregulates human endothelial cell expression of Del-1 by targeting a critical transcription factor, C/EBPbeta. Specifically, IL-17 causes GSK-3beta-dependent phosphorylation of C/EBPbeta, which is associated with diminished C/EBPbeta binding to the Del-1 promoter and suppressed Del-1 expression. This inhibitory action of IL-17 can be reversed at the GSK-3beta level by PI3K/Akt signalling induced by D-resolvins. The biological relevance of this regulatory network is confirmed in a mouse model of inflammatory periodontitis. Intriguingly, resolvin D1 (RvD1) confers protection against IL-17-driven periodontal bone loss in a Del 1-dependent manner, indicating an RvD1-Del-1 axis against IL-17-induced pathological inflammation. The dissection of signalling pathways regulating Del-1 expression provides potential targets to treat inflammatory diseases associated with diminished Del-1 expression, such as periodontitis and multiple sclerosis. PMID- 26374168 TI - Basic reproduction number of coxsackievirus type A6 and A16 and enterovirus 71: estimates from outbreaks of hand, foot and mouth disease in Singapore, a tropical city-state. AB - Coxsackievirus A6 (CV-A6), coxsackievirus A16 (CV-A16) and enterovirus 71 (EV A71) were the major enteroviruses causing nationwide hand, foot and mouth disease (HFMD) epidemics in Singapore in the last decade. We estimated the basic reproduction number (R 0) of these enteroviruses to obtain a better understanding of their transmission dynamics. We merged records of cases from HFMD outbreaks reported between 2007 and 2012 with laboratory results from virological surveillance. R 0 was estimated based on the cumulative number of reported cases in the initial growth phase of each outbreak associated with the particular enterovirus type. A total of 33 HFMD outbreaks were selected based on the inclusion criteria specified for our study, of which five were associated with CV A6, 13 with CV-A16, and 15 with EV-A71. The median R 0 was estimated to be 5.04 [interquartile range (IQR) 3.57-5.16] for CV-A6, 2.42 (IQR 1.85-3.36) for CV-A16, and 3.50 (IQR 2.36-4.53) for EV-A71. R 0 was not significantly associated with number of infected children (P = 0.86), number of exposed children (P = 0.94), and duration of the outbreak (P = 0.05). These enterovirus-specific R 0 estimates will be helpful in providing insights into the potential growth of future HFMD epidemics and outbreaks for timely implementation of disease control measures, together with disease dynamics such as severity of the cases. PMID- 26374171 TI - A histomorphometric assessment of collagen-stabilized anorganic bovine bone mineral in maxillary sinus augmentation - a prospective clinical trial. AB - OBJECTIVE: To histomorphometrically compare the use of collagen-stabilized anorganic bovine bone (ABBM-C) (test) to anorganic bovine bone + autogenous bone (ABBM + AB) (control) in maxillary sinus augmentation. MATERIALS AND METHODS: Forty (n = 40 sinuses) patients underwent sinus augmentation and received either control (20 sinuses) or test bone graft (20 sinuses). Bone samples were harvested from the augmented sinuses 5 months postgrafting. The samples were processed for histomorphometry, which assessed within the primary region of interest (ROI-1), the area fraction of new bone (%NB), graft particle osseointegration (% OI), residual graft (%RG), and soft tissue components (% STM). The same analysis was also carried out in a second region of interest (ROI-2) located in a zone 1 mm proximal to the previous maxillary sinus floor. RESULTS: In both ROI-1 and ROI-2, the mean % NB, %RG, and %STM in the control group were similar to mean values in the test group. The % OI was significantly greater in the control group (42.0 +/- 26.8) when compared to the test group (19.6 +/- 27.3) in ROI-2 (P < 0.05). No statistically significant differences were seen when ROI-1 and ROI-2 were compared except for improved %OI in ROI-2 in the control group. The mean proportion of lamellar bone to woven bone in the control group (1.22 +/- 1.48) was significantly greater than the test group (0.38 +/- 0.29) (P < 0.05). CONCLUSION: ABBM-C exhibited very similar histomorphometric parameters to the composite graft of ABBM + AB. The ABBM + AB group was more mature as indicated by the significantly greater proportion of lamellar bone when compared to the ABBM C. Improved % OI was seen in the zone proximal to the resident bony floor in the ABBM + AB group. Based on histological assessment, ABBM-C is a suitable bone substitute for the purposes of maxillary sinus augmentation. Its clinical utility may be indicated in cases of sinus membrane perforation and insufficient autogenous bone in the local area. PMID- 26374169 TI - Integrative Review of Genetic Factors Influencing Neurodevelopmental Outcomes in Preterm Infants. AB - Preterm infants are at elevated risk for a host of neurodevelopmental problems, including disorders that appear later in life. Gene-environment interactions and prematurity may combine to increase the risk for poor neurodevelopmental outcomes. Increasing evidence supports a genetic link to risk for atypical development; however, no genomic risk profiles are currently used for infants without apparent genetic disorders. The purpose of this review was to synthesize recent evidence of genetic associations with atypical neurodevelopmental outcomes that may affect preterm infants who do not have a rare genetic disease. Electronic and hand-search strategies were used to find relevant articles that were English-language, peer-reviewed primary research or meta-analysis reports published between July 2009 and July 2014, involving human participants. Articles included in the analysis (N = 29) used a wide range of study designs and methodologies, complicating the analysis. An integrative-review design was used to synthesize the data. Numerous genes (n = 43) and additional large deletion copy number variants were associated with neurodevelopmental outcomes, including cognition, attention, perception, psychiatric disease, autism spectrum disorder, cerebral palsy, infant behavior, and alterations in brain architecture. The creation of genetic risk profiles for complex disorders of neurodevelopment is presently hindered by inconsistent genetic-association evidence, methodological considerations, reporting problems, and lack of replication. However, several avenues of investigation offer promise, including large (>100 kb) copy number variants and the candidate genes MET, NRG3, and SLC6A4, each of which were reported to have associations with neurodevelopmental outcomes in multiple, high quality studies. PMID- 26374172 TI - Atenolol Renal Secretion Is Mediated by Human Organic Cation Transporter 2 and Multidrug and Toxin Extrusion Proteins. AB - Atenolol is a beta-blocker widely used in the treatment of hypertension. Atenolol is cleared predominantly by the kidney by both glomerular filtration and active secretion, but the molecular mechanisms involved in its renal secretion are unclear. Using a panel of human embryonic kidney cell lines stably expressing human organic cation transporter (hOCT) 1-3, human organic anion transporter (hOAT) 1, hOAT3, human multidrug and toxin extrusion protein (hMATE) 1, and hMATE2-K, we found that atenolol interacted with both organic cation and anion transporters. However, it is transported by hOCT1, hOCT2, hMATE1, and hMATE2-K, but not by hOCT3, hOAT1, and hOAT3. A detailed kinetic analysis coupled with absolute quantification of membrane transporter proteins by liquid chromatography tandem mass spectrometry revealed that atenolol is an excellent substrate for the renal transporters hOCT2, hMATE1, and hMATE2-K. The Km values for hOCT2, hMATE1, and hMATE2-K are 280 +/- 4, 32 +/- 5, and 76 +/- 14 MUM, respectively, and the calculated turnover numbers are 2.76, 0.41, and 2.20 s(-1), respectively. To demonstrate unidirectional transepithelial transport of atenolol, we developed and functionally validated a hOCT2/hMATE1 double-transfected Madin-Darby canine kidney cell culture model. Transwell studies showed that atenolol transport in the basal (B)-to-apical (A) direction is 27-fold higher than in the A-to-B direction, whereas its B-to-A/A-to-B transport ratio was only 2 in the vector transfected control cells. The overall permeability of atenolol in the B-to-A direction in hOCT2/hMATE1 cells was 44-fold higher than in control cells. Together, our data support that atenolol tubular secretion is mediated through the hOCT2/hMATEs secretion pathway and suggest a significant role of organic cation transporters in the disposition of an important antihypertensive drug. PMID- 26374173 TI - In Vitro Metabolism of Montelukast by Cytochrome P450s and UDP Glucuronosyltransferases. AB - Montelukast has been recommended as a selective in vitro and in vivo probe of cytochrome P450 (P450) CYP2C8 activity, but its selectivity toward this enzyme remains unclear. We performed detailed characterization of montelukast metabolism in vitro using human liver microsomes (HLMs), expressed P450s, and uridine 5' diphospho-glucuronosyltransferases (UGTs). Kinetic and inhibition experiments performed at therapeutically relevant concentrations reveal that CYP2C8 and CYP2C9 are the principal enzymes responsible for montelukast 36-hydroxylation to 1,2-diol. CYP3A4 was the main catalyst of montelukast sulfoxidation and stereoselective 21-hydroxylation, and multiple P450s participated in montelukast 25-hydroxylation. We confirmed direct glucuronidation of montelukast to an acyl glucuronide. We also identified a novel peak that appears consistent with an ether-glucuronide. Kinetic analysis in HLMs and experiments in expressed UGTs indicate that both metabolites were exclusively formed by UGT1A3. Comparison of in vitro intrinsic clearance in HLMs suggest that direct glucuronidation may play a greater role in the overall metabolism of montelukast than does P450-mediated oxidation, but the in vivo contribution of UGT1A3 needs further testing. In conclusion, our in vitro findings provide new insight toward montelukast metabolism. The utility of montelukast as a probe of CYP2C8 activity may be compromised owing to involvement of multiple P450s and UGT1A3 in its metabolism. PMID- 26374174 TI - Influence of contractile force on the architecture and morphology of the quadriceps femoris. AB - NEW FINDINGS: What is the central question of this study? Does contraction influence the fascicle length, pennation angle and effective physiological cross sectional area (eff PCSA) of the quadriceps femoris muscle? Is there a stronger relationship between eff PCSA and maximal strength if eff PCSA is measured during maximal contraction rather than at rest? What is the main finding and its importance? Fascicle length decreased, pennation angle increased and eff PCSA increased in a non-linear manner with isometric torque. The eff PCSA during maximal contraction and rest were correlated in a similar manner to maximal strength. The eff PCSA at rest is sufficient to characterize the muscle size strength relationship. The primary purpose of this study was to document the influence of muscle contraction on quadriceps femoris (QF) muscle architecture [fascicle length (Lf ) and pennation angle (thetap )] and effective physiological cross-sectional area (eff PCSA). Secondarily, we aimed to determine whether eff PCSA measured during maximal voluntary contraction (MVC) had a stronger relationship to maximal strength than eff PCSA at rest. Fifteen young men performed a series of voluntary knee-extension isometric ramp contractions. Isometric maximal voluntary torque (MVT) was recorded during separate MVCs. Measurements of architecture and eff PCSA of each constituent muscle of the QF and, subsequently, the whole QF were made at rest, during 20% increments of maximal voluntary torque and during an MVC. The QF muscle architecture and morphology changed in a curvilinear manner with relative torque (%MVT), with significant differences being observed between incremental torque levels for Lf , thetap and eff PCSA. Specifically, from rest to MVC, QF Lf decreased (-23.5 +/- 3.3%), whereas thetap increased (+39.7 +/- 6.6%). The QF eff PCSA was +26.5 +/- 5.7% greater during MVC than at rest. Similar moderate correlations existed for MVT and eff PCSA at rest (r = 0.519, P = 0.047) and for MVT and eff PCSA during MVC (r = 0.530, P = 0.042). Substantial changes in QF architecture (Lf , thetap ) and eff PCSA occur in a curvilinear manner with relative torque production. The eff PCSA during MVC was no more strongly associated with MVT than eff PCSA measured at rest, which implies that resting measurements of muscle size are suitable for characterizing the muscle size-strength relationship. PMID- 26374176 TI - Nutritional Impact of Dietary Plasma Proteins in Animals Undergoing Experimental Challenge and Implications for Patients with Inflammatory Bowel Disorders: A Meta analysis. AB - Studies administering plasma protein isolates (PPIs) to experimentally challenged animals have reported improvements in growth, food intake, and overall condition when compared with animals fed control diets, due in part to improvements in gut barrier function, normalization of cytokine signals, and support of enteric immune function. These and early clinical studies suggest that nutritional therapy with PPIs may similarly assist in restoring homeostasis to gut barrier function in humans experiencing mild or more acute enteropathic symptomatology such as irritable bowel syndrome and inflammatory bowel disease. This meta analysis evaluated the ability of PPIs to promote weight gain and food intake in weanling animals, primarily piglets, after oral challenge with various enteric pathogens or bacterial toxins. MEDLINE, EMBASE, and PubMed were searched from 1980 through August 2012 for specified terms and keywords. Twenty-nine articles retrieved through this process were evaluated; 11 studies including 13 experiments were selected for inclusion in the analysis. The meta-analysis included descriptive analyses and methods for combining P values for the primary endpoint, average daily growth (ADG) at week 1, and secondary endpoints including ADG, average daily feed intake (ADFI), and gain to feed ratio (G:F) at weeks 1 and 2 and at the end of study. Primary and secondary endpoint analyses of growth (ADG, ADFI, and G:F) were significant (P < 0.01). The proinflammatory cytokines interleukin (IL) 1beta, IL-6, and tumor necrosis factor alpha were significantly lower in animals fed dietary PPIs. Additional research in patients experiencing symptoms of enteropathy will further characterize the benefits of PPIs in clinical populations. PMID- 26374177 TI - Vitamin B-12 and Perinatal Health. AB - Vitamin B-12 deficiency (<148 pmol/L) is associated with adverse maternal and neonatal outcomes, including developmental anomalies, spontaneous abortions, preeclampsia, and low birth weight (<2500 g). The importance of adequate vitamin B-12 status periconceptionally and during pregnancy cannot be overemphasized, given its fundamental role in neural myelination, brain development, and growth. Infants born to vitamin B-12-deficient women may be at increased risk of neural tube closure defects, and maternal vitamin B-12 insufficiency (<200 pmol/L) can impair infant growth, psychomotor function, and brain development, which may be irreversible. However, the underlying causal mechanisms are unknown. This review was conducted to examine the evidence that links maternal vitamin B-12 status and perinatal outcomes. Despite the high prevalence of vitamin B-12 deficiency and associated risk of pregnancy complications, few prospective studies and, to our knowledge, only 1 randomized trial have examined the effects of vitamin B-12 supplementation during pregnancy. The role of vitamin B-12 in the etiology of adverse perinatal outcomes needs to be elucidated to inform public health interventions. PMID- 26374178 TI - Folate-Dependent Purine Nucleotide Biosynthesis in Humans. AB - Purine nucleotide biosynthesis de novo (PNB) requires 2 folate-dependent transformylases-5'-phosphoribosyl-glycinamide (GAR) and 5'-phosphoribosyl-5 aminoimidazole-4-carboxamide (AICAR) transformylases-to introduce carbon 8 (C8) and carbon 2 (C2) into the purine ring. Both transformylases utilize 10 formyltetrahydrofolate (10-formyl-H4folate), where the formyl-carbon sources include ring-2-C of histidine, 3-C of serine, 2-C of glycine, and formate. Our findings in human studies indicate that glycine provides the carbon for GAR transformylase (exclusively C8), whereas histidine and formate are the predominant carbon sources for AICAR transformylase (C2). Contrary to the previous notion, these carbon sources may not supply a general 10-formyl-H4folate pool, which was believed to equally provide carbons to C8 and C2. To explain these phenomena, we postulate that GAR transformylase is in a complex with the trifunctional folate-metabolizing enzyme (TFM) and serine hydroxymethyltransferase to channel carbons of glycine and serine to C8. There is no evidence for channeling carbons of histidine and formate to AICAR transformylase (C2). GAR transformylase may require the TFM to furnish 10-formyl H4folate immediately after its production from serine to protect its oxidation to 10-formyldihydrofolate (10-formyl-H2folate), whereas AICAR transformylase can utilize both 10-formyl-H2folate and 10-formyl-H4folate. Human liver may supply AICAR to AICAR transformylase in erythrocytes/erythroblasts. Incorporation of ring-2-C of histidine and formate into C2 of urinary uric acid presented a circadian rhythm with a peak in the morning, which corresponds to the maximum DNA synthesis in the bone marrow, and it may be useful in the timing of the administration of drugs that block PNB for the treatment of cancer and autoimmune disease. PMID- 26374179 TI - Plasma Transthyretin as a Biomarker of Lean Body Mass and Catabolic States. AB - Plasma transthyretin (TTR) is a plasma protein secreted by the liver that circulates bound to retinol-binding protein 4 (RBP4) and its retinol ligand. TTR is the sole plasma protein that reveals from birth to old age evolutionary patterns that are closely superimposable to those of lean body mass (LBM) and thus works as the best surrogate analyte of LBM. Any alteration in energy-to protein balance impairs the accretion of LBM reserves and causes early depression of TTR production. In acute inflammatory states, cytokines induce urinary leakage of nitrogenous catabolites, deplete LBM stores, and cause an abrupt decrease in TTR and RBP4 concentrations. As a result, thyroxine and retinol ligands are released in free form, creating a second frontline that strengthens that primarily initiated by cytokines. Malnutrition and inflammation thus keep in check TTR and RBP4 secretion by using distinct and unrelated physiologic pathways, but they operate in concert to downregulate LBM stores. The biomarker complex integrates these opposite mechanisms at any time and thereby constitutes an ideally suited tool to determine residual LBM resources still available for metabolic responses, hence predicting outcomes of the most interwoven disease conditions. PMID- 26374180 TI - Plant-Based and Plant-Rich Diet Patterns during Gestation: Beneficial Effects and Possible Shortcomings. AB - Environmental and lifestyle factors are known to play an important role during gestation, determining newborns' health status and influencing their risk of being subject to certain noncommunicable diseases later in life. In particular, maternal nutritional patterns characterized by a low intake of plant-derived foods could increase the risk of gestation-related issues, such as preeclampsia and pregravid obesity, increase genotoxicant susceptibility, and contribute to the onset of pediatric diseases. In particular, the risk of pediatric wheeze, diabetes, neural tube defects, orofacial clefts, and some pediatric tumors seems to be reduced by maternal intake of adequate amounts of vegetables, fruits, and selected antioxidants. Nevertheless, plant-based diets, like any other diet, if improperly balanced, could be deficient in some specific nutrients that are particularly relevant during gestation, such as n-3 (omega-3) fatty acids, vitamin B-12, iron, zinc, and iodine, possibly affecting the offspring's health state. Here we review the scientific literature in this field, focusing specifically on observational studies in humans, and highlight protective effects elicited by maternal diets enriched in plant-derived foods and possible issues related to maternal plant-based diets. PMID- 26374175 TI - Advances in Our Understanding of Oxylipins Derived from Dietary PUFAs. AB - Oxylipins formed from polyunsaturated fatty acids (PUFAs) are the main mediators of PUFA effects in the body. They are formed via cyclooxygenase, lipoxygenase, and cytochrome P450 pathways, resulting in the formation of prostaglandins, thromboxanes, mono-, di-, and tri-hydroxy fatty acids (FAs), epoxy FAs, lipoxins, eoxins, hepoxilins, resolvins, protectins (also called neuroprotectins in the brain), and maresins. In addition to the well-known eicosanoids derived from arachidonic acid, recent developments in lipidomic methodologies have raised awareness of and interest in the large number of oxylipins formed from other PUFAs, including those from the essential FAs and the longer-chain n-3 (omega-3) PUFAs. Oxylipins have essential roles in normal physiology and function, but can also have detrimental effects. Compared with the oxylipins derived from n-3 PUFAs, oxylipins from n-6 PUFAs generally have greater activity and more inflammatory, vasoconstrictory, and proliferative effects, although there are notable exceptions. Because PUFA composition does not necessarily reflect oxylipin composition, comprehensive analysis of the oxylipin profile is necessary to understand the overall physiologic effects of PUFAs mediated through their oxylipins. These analyses should include oxylipins derived from linoleic and alpha-linolenic acids, because these largely unexplored bioactive oxylipins constitute more than one-half of oxylipins present in tissues. Because collated information on oxylipins formed from different PUFAs is currently unavailable, this review provides a detailed compilation of the main oxylipins formed from PUFAs and describes their functions. Much remains to be elucidated in this emerging field, including the discovery of more oxylipins, and the understanding of the differing biological potencies, kinetics, and isomer-specific activities of these novel PUFA metabolites. PMID- 26374181 TI - Reciprocal Compensation to Changes in Dietary Intake and Energy Expenditure within the Concept of Energy Balance. AB - An imbalance between energy intake and energy expenditure is the primary etiology for excess weight gain. Increased energy expenditure via exercise and energy restriction via diet are commonly used approaches to induce weight loss. Such behavioral interventions, however, have generally resulted in a smaller than expected weight loss, which in part has been attributed to compensatory adaptations in other components contributing to energy balance. Current research points to a loose coupling between energy intake and energy expenditure on a daily basis, and evidence for long-term adaptations has been inconsistent. The lack of conclusive evidence on compensatory adaptations in response to alterations in energy balance can be attributed to differences in intervention type and study population. Physical activity (PA) levels may be reduced in response to aerobic exercise but not in response to resistance exercise. Furthermore, athletic and lean adults have been shown to increase their energy intake in response to exercise, whereas no such response was observed in obese adults. There is also evidence that caloric restriction is associated with a decline in PA. Generally, humans seem to be better equipped to defend against weight loss than avoid weight gain, but results also show a large individual variability. Therefore, individual differences rather than group means should be explored to identify specific characteristics of "compensators" and "noncompensators." This review emphasizes the need for more research with simultaneous measurements of all major components contributing to energy balance to enhance the understanding of the regulation of energy balance, which is crucial to address the current obesity epidemic. PMID- 26374184 TI - Anthocyanins. PMID- 26374182 TI - Intravenous Lipid Emulsions in Parenteral Nutrition. AB - Fat is an important macronutrient in the human diet. For patients with intestinal failure who are unable to absorb nutrients via the enteral route, intravenous lipid emulsions play a critical role in providing an energy-dense source of calories and supplying the essential fatty acids that cannot be endogenously synthesized. Over the last 50 y, lipid emulsions have been an important component of parenteral nutrition (PN), and over the last 10-15 y many new lipid emulsions have been manufactured with the goal of improving safety and efficacy profiles and achieving physiologically optimal formulations. The purpose of this review is to provide a background on the components of lipid emulsions, their role in PN, and to discuss the lipid emulsions available for intravenous use. Finally, the role of parenteral fat emulsions in the pathogenesis and management of PN associated liver disease in PN-dependent pediatric patients is reviewed. PMID- 26374186 TI - Hyson's Review Ignores Long-Term Research and Recent Global Guidelines That Recommend No More Than 4 Ounces of Fruit Juice a Day Due to Adverse Health Effects. PMID- 26374187 TI - Erratum for Konstantinidou et al. Personalized nutrition and cardiovascular disease prevention: from Framingham to PREDIMED. Adv Nutr 2014;5:368S-71S. PMID- 26374183 TI - Obesity in Childhood Cancer Survivors: Call for Early Weight Management. AB - A high prevalence of obesity and cardiometabolic conditions has been increasingly recognized in childhood cancer survivors. In particular, survivors of pediatric acute lymphoblastic leukemia have been found to be at risk of becoming overweight or obese early in treatment, with increases in weight maintained throughout treatment and beyond. Nutrition plays an important role in the etiology of obesity and cardiometabolic conditions and is among the few modifiable factors that can prevent or delay the early onset of these chronic conditions. However, nutritional intake in childhood cancer survivors has not been adequately examined and the evidence is built on data from small cohorts of survivors. In addition, the long-term impact of cancer diagnosis and treatment on survivors' nutritional intake as well as how survivors' nutritional intake is associated with chronic health conditions have not been well quantified in large-scale studies. Promoting family-based healthy lifestyles, preferably at a sensitive window of unhealthy weight gain, is a priority for preventing the early onset of obesity and cardiometabolic conditions in childhood cancer survivors. PMID- 26374188 TI - Mesoporous CLEAs-silica composite microparticles with high activity and enhanced stability. AB - A novel enzyme immobilization approach was used to generate mesoporous enzymes silica composite microparticles by co-entrapping gelatinized starch and cross linked phenylalanine ammonia lyase (PAL) aggregates (CLEAs) containing gelatinized starch into biomemitic silica and subsequently removing the starch by alpha-amylase treatment. During the preparation process, the gelatinzed starch served as a pore-forming agent to create pores in CLEAs and biomimetic silica. The resulting mesoporous CLEAs-silica composite microparticles exhibited higher activity and stability than native PAL, conventional CLEAs, and PAL encapsulated in biomimetic silica. Furthermore, the mesoporous CLEAs-silica composite microparticles displayed good reusability due to its suitable size and mechanical properties, and had excellent stability for storage. The superior catalytic performances were attributed to the combinational unique structure from the intra cross-linking among enzyme aggregates and hard mesoporous silica shell, which not only decreased the enzyme-support negative interaction and mass-transfer limitations, but also improved the mechanical properties and monodispersity. This approach will be highly beneficial for preparing various bioactive mesoporous composites with excellent catalytic performance. PMID- 26374189 TI - Two novel POC1A mutations in the primordial dwarfism, SOFT syndrome: Clinical homogeneity but also unreported malformations. AB - Primordial dwarfism encompasses rare conditions characterized by severe intrauterine growth retardation and growth deficiency throughout life. Recently, three POC1A mutations have been reported in six families with the primordial dwarfism, SOFT syndrome (Short stature, Onychodysplasia, Facial dysmorphism, and hypoTrichosis). Using a custom-designed Next-generation sequencing skeletal dysplasia panel, we have identified two novel homozygous POC1A mutations in two individuals with primordial dwarfism. The severe growth retardation and the facial profiles are strikingly similar between our patients and those described previously. However, one of our patients was diagnosed with severe foramen magnum stenosis and subglottic tracheal stenosis, malformations not previously associated with this syndrome. Our findings confirm that POC1A mutations cause SOFT syndrome and that mutations in this gene should be considered in patients with severe pre- and postnatal short stature, symmetric shortening of long bones, triangular facies, sparse hair and short, thickened distal phalanges. PMID- 26374190 TI - Fabrication of a live cell-containing multilayered polymer hydrogel membrane with micrometer-scale thickness to evaluate pharmaceutical activity. AB - We propose a spinning-assisted layer-by-layer method for simple fabrication of a multilayered polymer hydrogel membrane that contains living cells. Hydrogel formation occurred based on the spontaneous cross-linking reaction between two polymers in aqueous solution. A water-soluble 2-methacryloyloxyethyl phosphorylcholine polymer bearing phenylboronic acid groups (PMBV) and poly(vinyl alcohol) (PVA) were used as polymers for hydrogel membrane formation. Changing the number of hydrogel membrane layers, polymer concentration, spinning rate, and processing time for diffusion-dependent gelation of PMBV and PVA facilitated the regulation of the multilayered polymer hydrogel membrane thickness and morphology. We concluded that a multilayered polymer hydrogel membrane prepared using 5.0 wt% PMBV and 5.0 wt% PVA at a spinning rate of 2000 rpm was suitable for precise spatial control of cells in single layers. This multilayered polymer hydrogel membrane was used to prepare a single cell-laden layer to minimize barriers to the diffusion of bioactive compounds while preserving the three dimensional (3-D) context. The pharmaceutical effects of one of the anticancer agents, paclitaxel, on a human cervical cancer line, HeLa cells, were evaluated in vitro, and the usability of this culture model was demonstrated. PMID- 26374192 TI - Transthoracic versus transhiatal resection for esophageal adenocarcinoma of the lower esophagus: A value-based comparison. AB - BACKGROUND AND OBJECTIVE: Our objective was to compare clinical outcomes, costs, and resource use based on operative approach, transthoracic (TT) or transhiatal (TH), for resection of esophageal cancer. METHODS: This cohort analysis utilized the Surveillance, Epidemiology, and End Results--Medicare linked data from 2002 to 2009. Only adenocarcinomas of the lower esophagus were examined to minimize confounding. Medicare data was used to determine episode of care costs and resource use. Propensity score matching was used to control for identified confounders. Kaplan-Meier method and Cox-proportional hazard modeling were used to compare long-term survival. RESULTS: 537 TT and 405 TH resections were identified. TT and TH esophagectomy had similar complication rates (46.7% vs. 50.8%), operative mortality (7.9% vs 7.1%), and 90 days readmission rates (30.5% vs. 32.5%). However, TH was associated with shorter length of stay (11.5 vs. 13.0 days, P = 0.006) and nearly $1,000 lower cost of initial hospitalization (P = 0.03). No difference in 5-year survival was identified (33.5% vs. 36%, P = 0.75). CONCLUSIONS: TH esophagectomy was associated with lower costs and shorter length of stay in an elderly Medicare population, with similar clinical outcomes to TT. The TH approach to esophagectomy for distal esophageal adenocarcinoma may, therefore, provide greater value (quality/cost). PMID- 26374193 TI - Robust bioengineered 3D functional human intestinal epithelium. AB - Intestinal functions are central to human physiology, health and disease. Options to study these functions with direct relevance to the human condition remain severely limited when using conventional cell cultures, microfluidic systems, organoids, animal surrogates or human studies. To replicate in vitro the tissue architecture and microenvironments of native intestine, we developed a 3D porous protein scaffolding system, containing a geometrically-engineered hollow lumen, with adaptability to both large and small intestines. These intestinal tissues demonstrated representative human responses by permitting continuous accumulation of mucous secretions on the epithelial surface, establishing low oxygen tension in the lumen, and interacting with gut-colonizing bacteria. The newly developed 3D intestine model enabled months-long sustained access to these intestinal functions in vitro, readily integrable with a multitude of different organ mimics and will therefore ensure a reliable ex vivo tissue system for studies in a broad context of human intestinal diseases and treatments. PMID- 26374194 TI - Can children identify and achieve goals for intervention? A randomized trial comparing two goal-setting approaches. AB - AIM: The efficacy of two different goal-setting approaches (children's self identified goals and goals identified by parents) were compared on a goal directed, task-oriented intervention. METHOD: In this assessor-blinded parallel randomized trial, 34 children with disabilities (13 males, 21 females; mean age 9y, SD 1y 4mo) were randomized using concealed allocation to one of two 8-week, goal-directed, task-oriented intervention groups with different goal-setting approaches: (1) children's self-identified goals (n=18) using the Perceived Efficacy and Goal-Setting System, or (2) goals identified by parents (n=16) using the Canadian Occupational Performance Measure (COPM). Participants were recruited through eight paediatric rehabilitation centres and randomized between October 2011 and May 2013. The primary outcome measure was the Goal Attainment Scaling and the secondary measure, the COPM performance scale (COPM-P). Data were collected pre- and post-intervention and at the 5-month follow-up. RESULTS: There was no evidence of a difference in mean characteristics at baseline between groups. There was evidence of an increase in mean goal attainment (mean T score) in both groups after intervention (child-goal group: estimated mean difference [EMD] 27.84, 95% CI 22.93-32.76; parent-goal group: EMD 21.42, 95% CI 16.16 26.67). There was no evidence of a difference in the mean T scores post intervention between the two groups (EMD 6.42, 95% CI -0.80 to 13.65). These results were sustained at the 5-month follow-up. INTERPRETATION: Children's self identified goals are achievable to the same extent as parent-identified goals and remain stable over time. Thus children can be trusted to identify their own goals for intervention, thereby influencing their involvement in their intervention programmes. PMID- 26374195 TI - Repeat Procedures After Hybrid Thoracoscopic Ablation in the Setting of Longstanding Persistent Atrial Fibrillation: Electrophysiological Findings and 2 Year Clinical Outcome. AB - INTRODUCTION: In order to increase success rates of invasive treatment of persistent atrial fibrillation, the hybrid approach was developed, combining video-assisted thoracoscopic epicardial procedure with conventional endocardial catheter ablation. Currently, there are no reports of electrophysiological findings and clinical outcomes of repeat procedures after the hybrid approach. METHODS AND RESULTS: Out of 64 patients who were treated by hybrid ablation for persistent atrial fibrillation (AF), 14 underwent the repeat catheter ablation and were selected for this study. All 14 patients initially presented with longstanding persistent atrial fibrillation and markedly dilated atria. The hybrid procedure was performed in a single act and the mean time to redo procedure was 346 +/- 227 days. In 57% of patients indication for redo procedure was regular atrial tachycardia, and the rest presented with recurrent atrial fibrillation. In 36% of patients, recovered conduction was found along the previous ablation lesions. Only 9% of pulmonary veins were reconnected (0.36 veins per patient) and 7% of box lesions were not complete. The overall success rate at 2 years follow-up after the repeat procedure, including second repeat procedure and patients taking antiarrhythmic drugs, was 64% (57% without drugs and further ablation). One case of moderate pulmonary vein stenosis was detected as a consequence of hybrid procedure. CONCLUSION: Hybrid atrial fibrillation ablation results in durable lesions and high rates of chronic pulmonary vein isolation even after long-term follow-up. Most of the repeat procedures after the hybrid approach are related to left atrial flutters that could be successfully treated by catheter ablation. PMID- 26374196 TI - Overexpression of adenylate cyclase-associated protein 2 is a novel prognostic marker in malignant melanoma. AB - Malignant melanoma is one of the lethal malignant tumors worldwide. Previously we reported that adenylate cyclase-associated protein 2 (CAP2), which is a well conserved actin regulator, was overexpressed in hepatocellular carcinoma; however, CAP2 expression in other clinical cancers remains unclear. The aim of the current study was to clarify the clinicopathological significance of CAP2 overexpression in malignant melanoma. Immunohistochemical analyses revealed that many melanoma cells exhibited diffuse cytoplasmic expression of CAP2, whereas no normal melanocytes showed detectable immunostaining for CAP2. A high level of CAP2 expression was seen in 14 of 50 melanomas and was significantly correlated with greater tumor thickness and nodular melanoma subtypes. In addition, a high level of CAP2 expression was associated with poor overall survival in univariate and multivariate analyses. For 13 patients, samples of primary and metastatic melanoma tissue were available: four patients exhibited higher levels of CAP2 expression in metastatic tumor compared to the primary site, whereas no patient showed lower levels of CAP2 expression in metastatic melanomas. Our findings show that CAP2 overexpression is a novel prognostic marker in malignant melanoma and that CAP2 expression seems to increase stepwise during tumor progression, suggesting the involvement of CAP2 in the aggressive behavior of malignant melanoma. PMID- 26374197 TI - Limited evidence that cancer susceptibility regions are preferential targets for somatic mutation. AB - BACKGROUND: Genome wide-association studies have successfully identified several hundred independent loci harboring common cancer susceptibility alleles that are distinct from the more than 110 cancer predisposition genes. The latter are generally characterized by disruptive mutations in coding genes that have been established as 'drivers' of cancer in large somatic sequencing studies. We set out to determine whether, similarly, common cancer susceptibility loci map to genes that have altered frequencies of mutation. RESULTS: In our analysis of the intervals defined by the cancer susceptibility markers, we observed that cancer susceptibility regions have gene mutation frequencies comparable to background mutation frequencies. Restricting analyses to genes that have been determined to be pleiotropic across cancer types, genes affected by expression quantitative trait loci, or functional genes indicates that most cancer susceptibility genes classified into these subgroups do not display mutation frequencies that deviate from those expected. We observed limited evidence that cancer susceptibility regions that harbor common alleles with small estimated effect sizes are preferential targets for altered somatic mutation frequencies. CONCLUSIONS: Our findings suggest a complex interplay between germline susceptibility and somatic mutation, underscoring the cumulative effect of common variants on redundant pathways as opposed to driver genes. Complex biological pathways and networks likely link these genetic features of carcinogenesis, particularly as they relate to distinct polygenic models for each cancer type. PMID- 26374198 TI - Engineering of Kuma030: A Gliadin Peptidase That Rapidly Degrades Immunogenic Gliadin Peptides in Gastric Conditions. AB - Celiac disease is characterized by intestinal inflammation triggered by gliadin, a component of dietary gluten. Oral administration of proteases that can rapidly degrade gliadin in the gastric compartment has been proposed as a treatment for celiac disease; however, no protease has been shown to specifically reduce the immunogenic gliadin content, in gastric conditions, to below the threshold shown to be toxic for celiac patients. Here, we used the Rosetta Molecular Modeling Suite to redesign the active site of the acid-active gliadin endopeptidase KumaMax. The resulting protease, Kuma030, specifically recognizes tripeptide sequences that are found throughout the immunogenic regions of gliadin, as well as in homologous proteins in barley and rye. Indeed, treatment of gliadin with Kuma030 eliminates the ability of gliadin to stimulate a T cell response. Kuma030 is capable of degrading >99% of the immunogenic gliadin fraction in laboratory simulated gastric digestions within physiologically relevant time frames, to a level below the toxic threshold for celiac patients, suggesting great potential for this enzyme as an oral therapeutic for celiac disease. PMID- 26374200 TI - Advances in pharmacotherapy for hyperphosphatemia in renal disease. AB - INTRODUCTION: Hyperphosphatemia in chronic kidney disease (CKD) is considered as an independent risk factor for surrogate clinical end points like vascular calcification (VC) and bone disease, or hard clinical outcomes like cardiovascular events. Various treatment options are available for phosphate removal or reduction. Calcium-based phosphate binders (CBB) with their possible positive calcium balance became culprits for progressive VC and increased mortality risk. Non-calcium-based binders (NCBB) treatment allowed a comparable control of hyperphosphatemia with a lower risk of hypercalcemia and a slower progression of VC. Recent data have shown a 22% risk reduction in all-cause mortality with NCBB compared to CBB treatment. The appropriate timing of phosphate binder initiation in CKD patients is still unclear. Recent reports in patients with CKD stages 3b-4 showed increased VC progression when actively treated compared to placebo and a positive calcium, but no negative phosphate balance. AREAS COVERED: This review discusses the advantages and disadvantages of the pharmacological options to treat hyperphosphatemia. EXPERT OPINION: The use of phosphate binders is essential in preventing morbidity and mortality in dialysis patients. The choice of phosphate binder takes into account CKD stage, the presence of other components of CKD-mineral and bone disorders, concomitant therapies and drug side-effect profile. PMID- 26374199 TI - Sequential azacitidine plus lenalidomide in previously treated elderly patients with acute myeloid leukemia and higher risk myelodysplastic syndrome. AB - The outcome of sequential azacitidine with lenalidomide has not been reported in previously treated patients with acute myeloid leukemia (AML) and higher risk myelodysplastic syndrome (MDS). This study describes a phase 2 study evaluating the safety and efficacy of this combination in elderly patients with AML and MDS with prior hypomethylating agent (HMA) and/or immunomodulatory agent exposure. Patients were treated on a 42-day cycle with azacitidine at 75 mg/m2 SQ/IV daily on days 1-7, followed by lenalidomide 50 mg orally daily on days 8-28. The median number of treatment cycles on study was two (range = 1-11). Of 32 evaluable patients, the overall response rate was 25%. Neutropenic fever was the most common serious adverse event, but overall the combination was well-tolerated. The median overall survival (OS) for responders vs non-responders was 9.8 vs 4.0 months, respectively (HR = 0.36, p = 0.016). In conclusion, this combination demonstrated modest clinical activity in this poor risk population. PMID- 26374201 TI - The effect of diet on serum 25-hydroxyvitamin D concentrations in dogs. AB - BACKGROUND: Vitamin D (vitD) deficiency is linked to many disease states including rickets and cancer, and vitD supplementation to improve response to cancer therapy has been explored. Supplementation may be most appropriate for dogs with suboptimal vitD concentrations. In dogs, the primary source of vitD is diet (predominantly via commercial dog food). Our goal was to determine how food source and supplements affect 25(OH)D concentrations, the storage form of vitD. Serum was collected from clinically healthy dogs, and pet owners were surveyed about food source and supplements. Serum 25(OH)D concentration was measured using a quantitative chemiluminescent assay (LIASON, DiaSorin, Stillwater, MN). RESULTS: Dogs (n = 320) were tested for serum 25(OH)D concentrations (range 9.5 249.2 ng/mL). Dogs were fed commercial diets from forty different manufactures (n = 292); additionally some dogs were fed homemade diets (n = 18) or a combination of commercial and homemade diets (n = 10). Median serum 25(OH)D concentrations in dogs fed commercial foods ranged from 47.4 to 100.1 ng/mL with an overall median of 67.9 ng/ml (CV 29%). Analysis for differences among manufacturers was significant (P = 0.0006). Serum 25(OH)D concentrations amongst dogs fed homemade diets had the largest range (9.5-129 ng/mL) and the lowest value (9.5 ng/mL). Dogs receiving salmon oil as a supplement (n = 22) had significantly higher serum 25(OH)D (on average a 19.6 ng/mL increase) than those not receiving a supplement (P = 0.007). CONCLUSIONS: Serum 25(OH)D concentrations in dogs vary widely which likely reflects varying dietary vitD content. Notable differences exist among manufacturers and brands and may reflect differences in proprietary formulations. Given the variability of measured serum 25(OH)D concentrations in dogs and the importance vitD appears to have on health status, dietary vitD content should be optimized. PMID- 26374202 TI - Rhizobium marinum sp. nov., a malachite-green-tolerant bacterium isolated from seawater. AB - A motile, Gram-stain-negative, non-pigmented bacterial strain, designated MGL06T, was isolated from seawater of the South China Sea on selection medium containing 0.1 % (w/v) malachite green. Strain MGL06T showed highest 16S rRNA gene sequence similarity to Rhizobium vignae CCBAU 05176T (97.2 %), and shared 93.2-96.9 % with the type strains of other recognized Rhizobium species. Phylogenetic analyses based on 16S rRNA and housekeeping gene sequences showed that strain MGL06T belonged to the genus Rhizobium. Mean levels of DNA-DNA relatedness between strain MGL06T and R. vignae CCBAU 05176T, Rhizobium huautlense S02T and Rhizobium alkalisoli CCBAU 01393T were 20 +/- 3, 18 +/- 2 and 14 +/- 3 %, respectively, indicating that strain MGL06T was distinct from them genetically. Strain MGL06T did not form nodules on three different legumes, and the nodD and nifH genes were also not detected by PCR or based on the draft genome sequence. Strain MGL06T contained Q-10 as the predominant ubiquinone. The major fatty acid was C18 : 1omega7c/C18 : 1omega6c with minor amounts of C19 : 0 cyclo omega8c, C16 : 0 and C18 : 1omega7c 11-methyl. Polar lipids of strain MGL06T included unknown glycolipids, phosphatidylcholine, aminolipid, phosphatidylglycerol, phosphatidylethanolamine, diphosphatidylglycerol, an unknown polar lipid and aminophospholipid. Based on its phenotypic and genotypic data, strain MGL06T represents a novel species of the genus Rhizobium, for which the name Rhizobium marinum sp. nov. is proposed. The type strain is MGL06T ( = MCCC 1A00836T = JCM 30155T). PMID- 26374203 TI - The Tobacco Status Project (TSP): Study protocol for a randomized controlled trial of a Facebook smoking cessation intervention for young adults. AB - BACKGROUND: Tobacco use remains the leading cause of premature morbidity and mortality in the United States. Young adults are less successful at quitting, use cessation treatment less often than smokers of other ages, and can be a challenge to retain in treatment. Social media, integrated into the lives of many young adults, represents a promising strategy to deliver evidence-based smoking cessation treatment to a large, diverse audience. The goal of this trial is to test the efficacy of a stage-based smoking cessation intervention on Facebook for young adults age 18 to 25 on smoking abstinence, reduction in cigarettes smoked, and thoughts about smoking abstinence. METHODS/DESIGN: This is a randomized controlled trial. Young adult smokers throughout the United States are recruited online and randomized to either the 3 month Tobacco Status Project intervention on Facebook or a referral to a smoking cessation website. The intervention consists of assignment to a secret Facebook group tailored to readiness to quit smoking (precontemplation, contemplation, preparation), daily Facebook contacts tailored to readiness to quit smoking, weekly live counseling sessions, and for those in preparation, weekly Cognitive Behavioral Therapy counseling sessions on Facebook. Primary outcome measure is biochemically-verified 7-day point prevalence abstinence from smoking at posttreatment (3 months), 6, and 12 months. Secondary outcome measures are reduction of 50 % or more in cigarettes smoked, 24 h quit attempts, and commitment to abstinence at each time point. A secondary aim is to test, within the TSP condition, the effect of a monetary incentive at increasing engagement in the intervention. DISCUSSION: This randomized controlled trial is testing a novel Facebook intervention for treating young adults' tobacco use. If efficacious, the social media intervention could be disseminated widely and expanded to address additional health risks. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02207036 , May 13, 2014. PMID- 26374204 TI - A CYP21A2 based whole-cell system in Escherichia coli for the biotechnological production of premedrol. AB - BACKGROUND: Synthetic glucocorticoids like methylprednisolone (medrol) are of high pharmaceutical interest and represent powerful drugs due to their anti inflammatory and immunosuppressive effects. Since the chemical hydroxylation of carbon atom 21, a crucial step in the synthesis of the medrol precursor premedrol, exhibits a low overall yield because of a poor stereo- and regioselectivity, there is high interest in a more sustainable and efficient biocatalytic process. One promising candidate is the mammalian cytochrome P450 CYP21A2 which is involved in steroid hormone biosynthesis and performs a selective oxyfunctionalization of C21 to provide the precursors of aldosterone, the main mineralocorticoid, and cortisol, the most important glucocorticoid. In this work, we demonstrate the high potential of CYP21A2 for a biotechnological production of premedrol, an important precursor of medrol. RESULTS: We successfully developed a CYP21A2-based whole-cell system in Escherichia coli by coexpressing the cDNAs of bovine CYP21A2 and its redox partner, the NADPH dependent cytochrome P450 reductase (CPR), via a bicistronic vector. The synthetic substrate medrane was selectively 21-hydroxylated to premedrol with a max. yield of 90 mg L(-1) d(-1). To further improve the biocatalytic activity of the system by a more effective electron supply, we exchanged the CPR with constructs containing five alternative redox systems. A comparison of the constructs revealed that the redox system with the highest endpoint yield converted 70 % of the substrate within the first 2 h showing a doubled initial reaction rate compared with the other constructs. Using the best system we could increase the overall yield of premedrol to a maximum of 320 mg L(-1) d(-1) in shaking flasks. Optimization of the biotransformation in a bioreactor could further improve the premedrol gain to a maximum of 0.65 g L(-1) d(-1). CONCLUSIONS: We successfully established a CYP21-based whole-cell system for the biotechnological production of premedrol, a pharmaceutically relevant glucocorticoid, in E. coli and could improve the system by optimizing the redox system concerning reaction velocity and endpoint yield. This is the first step for a sustainable replacement of a complicated chemical low-yield hydroxylation by a biocatalytic cytochrome P450-based whole-cell system. PMID- 26374205 TI - Incidence of differentiated thyroid cancer in Canada by City of residence. AB - BACKGROUND: Thyroid cancer incidence in Canada is increased in high socioeconomic groups, and in urban compared with rural areas. The objective of this study was to analyze patterns in thyroid cancer incidence across Canada, particularly with respect to the major urban areas across the country, to identify whether there are any discrepancies in thyroid cancer incidence between Canadian cities. METHODS: Cases were drawn from the Canadian Cancer Registry. Demographic and socioeconomic information were extracted from the Canadian Census of Population data. We linked cases to income quintiles (InQs) by patients' postal codes, and categorized residence by census metropolitan area ((CMA), population >100,000). Within the Toronto CMA we further classified by census subdivision (CSD). RESULTS: There were a total of 33 CMAs across the country. After controlling for demographic and socio-economic factors, we found that the Toronto CMA had an IRR of thyroid cancer that was significantly higher than all other CMAs across the country. For 70% of CMAs and CAs across Canada, the IRR for thyroid cancer was less than half of the IRR for thyroid cancer in the Toronto CMA. As Toronto is one of the largest CMAs, we then subdivided the Toronto area into CSDs to examine how incidence of thyroid cancer varies within this large area. The Toronto City core was used as the reference category and all other areas were compared directly to it. In doing so, we found that a contiguous area of three CSDs North of Toronto had higher IRRs compared with the Toronto city core: Markham, Vaughan and Richmond Hill. CONCLUSIONS: After controlling for demographic and socioeconomic factors, we found that the Toronto CMA has the highest incidence of thyroid cancer nationwide. Several explanations could account for this discrepancy including increased detection due to increased access to imaging, differences in ethnicity or environmental exposures. PMID- 26374206 TI - Chronically ill patients' self-management abilities to maintain overall well being: what is needed to take the next step in the primary care setting? AB - BACKGROUND: Although widespread problems in patient-professional interaction and insufficient support of patients' self-management abilities have been recognized, research investigating the relationships among care quality, productive interaction, and self-management abilities to maintain overall well-being is lacking. Furthermore, studies have revealed differences in these characteristics among certain groups (e.g., less-educated and older patients). This longitudinal study thus aimed to identify relationships among background characteristics, quality of care, productivity of patient-professional interaction, and self management abilities to maintain overall well-being in chronically ill patients participating in 18 Dutch disease management programs. METHODS: This longitudinal study included patients participating in 18 Dutch disease management programs. Surveys were administered in 2011 (T1; n = 2191 (out of 4693), 47 % response rate) and 2012 (T2: n = 1722 (out of 4350), 40 % response rate). A total of 1279 patients completed questionnaires at both timepoints (T1 and T2) (27 % response rate). Self-management abilities to maintain well-being were measured using the short (18-item) version of the Self-Management Ability Scale (SMAS-S), patients' perceptions of the productivity of interactions with health care professionals were assessed with the relational coordination instrument and the short (11-item) version of the Patient Assessment of Chronic Illness Care (PACIC-S) was used to assess patients' perceptions of the quality of chronic care delivery. RESULTS: Perceived and objective quality of care and the productivity of patient professional interaction were found to be related to patients' self-management abilities to maintain overall well-being. These abilities were related negatively to and significantly predicted by low educational level, single status, and older age, despite the mediating role of productive interaction in their relationship with patients' perceptions of care quality. CONCLUSIONS: These findings suggest that patient-professional interaction is not yet sufficiently productive to successfully protect against the deterioration of self-management abilities in some groups of chronically ill patients, although such interaction and high quality care are important factors in such protection. Improvement of the quality of chronic care delivery should thus always be accompanied by investment in high quality communication and patient-professional relationships. PMID- 26374208 TI - Participatory definition of breeding objectives for sheep breeds under pastoral systems--the case of Red Maasai and Dorper sheep in Kenya. AB - Crossing local breeds with exotic breeds may be an option for increased livestock productivity. However, there is a risk for endangerment of the local breeds. One such case is in Kenya where the imported Dorper breed is used for crossbreeding with Red Maasai sheep. The aim of this study was to investigate farmers' trait preferences as a basis for determination of breeding objectives for Red Maasai and Dorper sheep at two sites, Amboseli and Isinya, in Kenya. Within their own flock, each farmer identified three ewes representing the best, average and poorest within each breed group: Red Maasai, Dorper and Crosses. Farmers gave reasons for their ranking. Body measurements and weights were also taken. At the harshest site, Amboseli, differences between breed groups in body weight were small and breeds were equally preferred. In Isinya, where environmental conditions are better and farmers are more market oriented, Dorper and Crosses had significantly higher body weights and market prices and were thus preferred by the farmers. Red Maasai were preferred for their maternal and adaptive traits. Breeding objectives should emphasize growth traits and milk production in both breeds at both sites. Body condition needs to be specifically considered in the breeding objectives for sheep in Amboseli, whereas adaptive traits need to be generally emphasized in Dorper. PMID- 26374207 TI - Expression of the retinoic acid catabolic enzyme CYP26B1 in the human brain to maintain signaling homeostasis. AB - Retinoic acid (RA) is a potent regulator of gene transcription via its activation of a set of nuclear receptors controlling transcriptional activation. Precise maintenance of where and when RA is generated is essential and achieved by local expression of synthetic and catabolic enzymes. The catabolic enzymes Cyp26a1 and Cyp26b1 have been studied in detail in the embryo, where they limit gradients of RA that form patterns of gene expression, crucial for morphogenesis. This paracrine role of RA has been assumed to occur in most tissues and that the RA synthetic enzymes release RA at a site distant from the catabolic enzymes. In contrast to the embryonic CNS, relatively little is known about RA metabolism in the adult brain. This study investigated the distribution of Cyp26a1 and Cyp26b1 transcripts in the rat brain, identifying several novel regions of expression, including the cerebral cortex for both enzymes and striatum for Cyp26b1. In vivo use of a new and potent inhibitor of the Cyp26 enzymes, ser 2-7, demonstrated a function for endogenous Cyp26 in the brain and that hippocampal RA levels can be raised by ser 2-7, altering the effect of RA on differential patterning of cell proliferation in the hippocampal region of neurogenesis, the subgranular zone. The expression of CYP26A1 and CYP26B1 was also investigated in the adult human brain and colocalization of CYP26A1 and the RA synthetic enzyme RALDH2 indicated a different, autocrine role for RA in human hippocampal neurons. Studies with the SH-SY5Y human neuroblastoma cell line implied that the co-expression of RA synthetic and catabolic enzymes maintains retinoid homeostasis within neurons. This presents a novel view of RA in human neurons as part of an autocrine, intracellular signaling system. PMID- 26374209 TI - Seroprevalence and risk factors for brucellosis in cattle in selected districts of Jimma zone, Ethiopia. AB - A cross-sectional study was carried out in Jimma town and Chora Botor district of Jimma zone from February 2014 to May 2014 to determine seroprevalence and risk factors of brucellosis in cattle. A total of 348 blood samples (174 each from zebu and crossbreed) were collected. The sera were separated and screened by Rose Bengal plate test (RBPT), and positive sera were retested by complement fixation test (CFT) for confirmation. The overall seroprevalence of bovine brucellosis was 1.4 and 0.3 % as tested by RBPT and CFT, respectively. The seroprevalence of bovine brucellosis in indigenous and crossbreed cattle was 1.1 and 0.6 % and 1.7 and 0 % using RBPT and CFT, respectively. Retained fetal membrane was the only risk factor found to be significantly associated with seropositivity of brucellosis in this study (p = 0.019). The overall seroprevalence of brucellosis was very low. However, due to the zoonotic and economic importance of the disease, prevention and control measures are required to stop further spread of the disease. To effectively implement this, the One Health (OH) is the most constructive approach we recommend. PMID- 26374210 TI - United States Food and Drug Administration Regulation of Gene and Cell Therapies. AB - The United States (US) Food and Drug Administration (FDA) is a regulatory agency that has oversight for a wide range of products entering the US market, including gene and cell therapies. The regulatory approach for these products is similar to other medical products within the United States and consists of a multitiered framework of statutes, regulations, and guidance documents. Within this framework, there is considerable flexibility which is necessary due to the biological and technical complexity of these products in general. This chapter provides an overview of the US FDA regulatory oversight of gene and cell therapy products. PMID- 26374211 TI - The National Institutes of Health Oversight of Human Gene Transfer Research: Enhancing Science and Safety. AB - The National Institutes of Health (NIH) oversight of human gene transfer research, which is defined as the deliberate transfer of recombinant and/or synthetic nucleic acid molecules to humans, originates with the NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules (NIH Guidelines). The NIH Guidelines, which were first published in the Federal Register almost 40 years ago, have been amended numerous times to remain responsive to scientific progress and to clearly define the responsibilities of NIH, the Recombinant DNA Advisory Committee (RAC), investigators, and institutions. Human gene transfer trials conducted at clinical sites in the United States (USA) are subject to the NIH Guidelines if they are conducted at, or sponsored by, an institution that receives any support for recombinant or synthetic nucleic acid research from the NIH. Human gene transfer trials conducted either in the USA or abroad are also subject to the NIH Guidelines if the investigational agent was developed with NIH funds and the institution that developed the investigational materials sponsors or participates in these projects. Trials are registered with the NIH Office Biotechnology Activities (OBA) and there are ongoing reporting requirements. Each new trial is reviewed by the RAC, and those that are novel or raise unique ethical or social issues are selected for review at quarterly public RAC meetings. The RAC also advises the NIH on policy and other matters relating to clinical gene transfer research and biosafety. PMID- 26374212 TI - Regulatory Oversight of Cell and Gene Therapy Products in Canada. AB - Health Canada regulates gene therapy products and many cell therapy products as biological drugs under the Canadian Food and Drugs Act and its attendant regulations. Cellular products that meet certain criteria, including minimal manipulation and homologous use, may be subjected to a standards-based approach under the Safety of Human Cells, Tissues and Organs for Transplantation Regulations. The manufacture and clinical testing of cell and gene therapy products (CGTPs) presents many challenges beyond those for protein biologics. Cells cannot be subjected to pathogen removal or inactivation procedures and must frequently be administered shortly after final formulation. Viral vector design and manufacturing control are critically important to overall product quality and linked to safety and efficacy in patients through concerns such as replication competence, vector integration, and vector shedding. In addition, for many CGTPs, the value of nonclinical studies is largely limited to providing proof of concept, and the first meaningful data relating to appropriate dosing, safety parameters, and validity of surrogate or true determinants of efficacy must come from carefully designed clinical trials in patients. Addressing these numerous challenges requires application of various risk mitigation strategies and meeting regulatory expectations specifically adapted to the product types. Regulatory cooperation and harmonisation at an international level are essential for progress in the development and commercialisation of these products. However, particularly in the area of cell therapy, new regulatory paradigms may be needed to harness the benefits of clinical progress in situations where the resources and motivation to pursue a typical drug product approval pathway may be lacking. PMID- 26374213 TI - Overview of the Regulatory Oversight Implemented by the French Regulatory Authorities for the Clinical Investigation of Gene Therapy and Cell Therapy Products. AB - Advanced therapy medicinal products, a new class of products with promising therapeutic effects, have been classified as medicinal products and as such should be developed according to a well-structured development plan, to establish their quality, safety and efficacy profile and conclude, at the time of the marketing authorisation evaluation, on a positive risk/benefit balance for patients. An important part of this development plan is achieved through clinical trials, which have also to be approved according to a well-established regulatory process, prior any initiation. This chapter is dedicated to describe the regulatory pathway to be followed in France, before initiating any clinical trial with those investigational advanced therapy medicinal products. In France, to get the final authorisation to initiate a clinical trial, the legislation imposes to run in parallel two independent but complementary authorisation procedures. The first procedure is aimed at assessing the ethical aspect of the biomedical research, while the second has to review the safety and regulatory aspects. A third procedure has to be envisaged where in case the investigational product consists or contains a genetically modified organism. The French system herein described is in line with the EU regulation on clinical trial and follows the respective deadlines for granting the final approval. The complexity of the procedure is in fact more due to the complexity of the products and protocols to be assessed than to the procedure itself which is now very close to the well known procedure applied routinely for more conventional chemical or biological candidate medicinal products. PMID- 26374214 TI - Regulation of Clinical Trials with Advanced Therapy Medicinal Products in Germany. AB - In the European Union, clinical trials for Advanced Therapy Medicinal Products are regulated at the national level, in contrast to the situation for a Marketing Authorisation Application, in which a centralised procedure is foreseen for these medicinal products. Although based on a common understanding regarding the regulatory requirement to be fulfilled before conduct of a clinical trial with an Advanced Therapy Investigational Medicinal Product, the procedures and partly the scientific requirements for approval of a clinical trial application differ between the European Union Member States. This chapter will thus give an overview about the path to be followed for a clinical trial application and the subsequent approval process for an Advanced Therapy Investigational Medicinal Product in Germany and will describe the role of the stakeholders that are involved. In addition, important aspects of manufacturing, quality control and non-clinical testing of Advanced Therapy Medicinal Products in the clinical development phase are discussed. Finally, current and future approaches for harmonisation of clinical trial authorisation between European Union Member States are summarised. PMID- 26374215 TI - Marketing Regulatory Oversight of Advanced Therapy Medicinal Products (ATMPs) in Europe: The EMA/CAT Perspective. AB - With the release of Regulation 1394/2007, a new framework for gene and cell therapy medicinal products and tissue-engineered products was established in the European Union. For all three product classes, called advanced therapy medicinal products, a centralised marketing authorisation became mandatory. The European Medicines Agency (EMA) together with its Committee for Advanced Therapies, Committee for Human Medicinal Products and the network of national agencies is responsible for scientific evaluation of the marketing authorisation applications. For a new application, data and information relating to manufacturing processes and quality control of the active substance and the final product have to be submitted for evaluation together with data from non-clinical and clinical safety and efficacy studies. Technical requirements for ATMPs are defined in the legislation, and guidance for different products is available through several EMA/CAT guidelines. Due to the diversity of ATMPs, a tailored approach for regulating these products is considered necessary. Thus, a risk based approach has been introduced for ATMPs allowing flexibility for the regulatory requirements. Since the regulatory framework for ATMPs was established, five products have been licenced in the European Union. However, the pipeline of new ATMPs is much bigger, as seen from the significant numbers of different products discussed by the CAT in scientific advice and classification procedures. In 2013, a public consultation on the ATMP Regulation was conducted by the European Commission, and the results were published in 2014. The report proposes several improvements for the current framework and established procedures for the regulation of ATMPs. PMID- 26374216 TI - Requirements for Clinical Trials with Gene Therapy and Transplant Products in Switzerland. AB - This chapter aims to describe and summarize the regulation of gene and cell therapy products in Switzerland and its legal basis. Product types are briefly described, as are Swiss-specific terminologies such as the term "transplant product," which means products manufactured from cells, tissues, or even whole organs. Although some parts of this chapter may show a guideline character, they are not legally binding, but represent the current thinking of Swissmedic, the Swiss Agency for Therapeutic Products. As so far the experience with marketing approval of gene therapy and cell therapy products in Switzerland is limited, this chapter focuses on the regulation of clinical trials conducted with these products. Quality, nonclinical, and clinical aspects are summarized separately for gene therapy products and transplant products. PMID- 26374217 TI - Regulatory Frameworks for Gene and Cell Therapies in Japan. AB - The regulations for the human use of advanced therapy medical products such as gene and cell therapy products have evolved in accordance with advance of clinical experience, scientific knowledge, and social acceptance to these technologies. In Japan, two laws, the Pharmaceuticals and Medical Devices (PMD) Act and the Act on the Safety of Regenerative Medicine (ASRM), were enacted in November 2014. The PMD Act defines regenerative medical products for the first time and introduces a system for the conditional and time-limited marketing authorization of regenerative medical products. Under ASRM, the responsibilities of medical institutions to ensure the safety and provide transparency of such medical technologies are described. Amendments to accompanying guidelines for these two Acts are currently in preparation. It is expected that the new legislative frameworks will promote the timely development of new products and technologies, to bring safe and effective regenerative medicines to Japanese patients. PMID- 26374218 TI - Regulatory Oversight of Gene Therapy and Cell Therapy Products in Korea. AB - The Ministry of Food and Drug Safety regulates gene therapy and cell therapy products as biological products under the authority of the Pharmaceutical Affairs Act. As with other medicinal products, gene therapy and cell therapy products are subject to approval for use in clinical trials and for a subsequent marketing authorization and to post-market surveillance. Research and development of gene therapy and cell therapy products have been progressing rapidly in Korea with extensive investment, offering great potential for the treatment of various serious diseases. To facilitate development of safe and effective products and provide more opportunities to patients suffering from severe diseases, several regulatory programs, such as the use of investigational products for emergency situations, fast-track approval, prereview of application packages, and intensive regulatory consultation, can be applied to these products. The regulatory approach for these innovative products is case by case and founded on science based review that is flexible and balances the risks and benefits. PMID- 26374219 TI - Regulation of Cell and Gene Therapy Medicinal Products in Taiwan. AB - Owing to the rapid and mature development of emerging biotechnology in the fields of cell culture, cell preservation, and recombinant DNA technology, more and more cell or gene medicinal therapy products have been approved for marketing, to treat serious diseases which have been challenging to treat with current medical practice or medicine. This chapter will briefly introduce the Taiwan Food and Drug Administration (TFDA) and elaborate regulation of cell and gene therapy medicinal products in Taiwan, including regulatory history evolution, current regulatory framework, application and review procedures, and relevant jurisdictional issues. Under the promise of quality, safety, and efficacy of medicinal products, it is expected the regulation and environment will be more flexible, streamlining the process of the marketing approval of new emerging cell or gene therapy medicinal products and providing diverse treatment options for physicians and patients. PMID- 26374220 TI - Regulatory Oversight of Cell- and Tissue-Based Therapeutic Products and Gene Therapy Products in Singapore. AB - The regulatory environment for cell- and tissue-based therapeutic products and gene therapy products is rapidly evolving and drug regulatory agencies are working towards establishing a risk-based system in the regulatory framework. Similarly in Singapore, a risk-based tiered approach has been applied whereby clinical trials and product licence of high-risk cell- and tissue-based therapeutic products (substantially manipulated products, products intended for nonhomologous use or combined products) and gene therapy products are regulated as medicinal products under the Medicines Act. There is no legal definition for cell- and tissue-based therapeutic and gene therapy products. The current working definition for a cell- and tissue-based therapeutic product is an article containing or consisting of an autologous or allogeneic human cell or tissue that are used for or administered to, or intended to be used for or administered to, human beings for the diagnosis, treatment, or prevention of human diseases or conditions. Gene therapy products are included under the current biological medicinal product definition. PMID- 26374221 TI - The Regulatory Pathway for Advanced Cell Therapy and Gene Therapy Products in Brazil: A Road to Be Built. AB - The regulation of cell therapy and gene therapy products is a major challenge for the Brazilian state. From a legal point of view, the legislative apparatus, including constitutional, prohibits the marketing and patent of human substances. From the point of view of the organization of the state bureaucracy, the responsibilities for the regulation of research and application of these technologies in humans may involve up to four different institutions. The National Agency for Health Surveillance (ANVISA) has been the protagonist in structuring the regulation of cell therapy and gene therapy in Brazil, and steps have been taken to ensure quality of these products. However, obstacles such as the commercialization of these therapies and the need to determine whether these products will be regulated following the assumptions adopted in Brazil for drugs and biological products or for human blood and tissues still remain. PMID- 26374223 TI - Cardiovascular Magnetic Resonance Imaging clarifies cardiac pathophysiology in early, asymptomatic diffuse systemic sclerosis. AB - BACKGROUND: Myopericardial inflammation, perfusion's defects and fibrosis are major causes of cardiac disease in scleroderma (SSc). We hypothesized that using inflammation and stress perfusion-fibrosis cardiovascular magnetic resonance (CMR), we can identify the pathophysiology of heart disease in asymptomatic diffuse SSc. PATIENTS-METHODS: 46 recently diagnosed, asymptomatic patients with diffuse SSc had a CMR examination using a 1.5T system. ECG gated breath hold cine and short tau inversion recovery (STIR) T2 images were initially acquired. If T2 ratio<2 a stress perfusion-fibrosis protocol was applied. If T2>2 a myocarditis protocol including early (EGE) and late (LGE) gadolinium imaging was applied. SSc patients' results were compared with age and sex-matched controls and patients with coronary artery disease (CAD). RESULTS: In 2/46 SSc with T2 ratio>2, the myocarditis protocol was positive for acute myocardial inflammation, who developed clinical signs of acute myocarditis shortly after the CMR evaluation. In the rest 44/46 with T2 ratio<2 the stress perfusion-fibrosis CMR identified a significant reduction in Myocardial Perfusion Reserve Index (MPRI) compared with matched controls (0.6+/-0.4 vs 3.2+/-0.8, p<0.001), but not with CAD (0.6+/-0.4 vs 0.86+/-0.46, p=NS) and correlated only with the presence of digital ulcers (p<0.05). The scar was diffused and greater compared to controls, but did not differ from that assessed in CAD. Two years follow up, available in 11/44 SSc, showed further asymptomatic MPRI deterioration in all and diffuse subendocardial LGE in 8/11, without any change in LV, RV volumes and ejection fractions. CONCLUSION: CMR may reveal severe cardiac involvement in early, asymptomatic diffuse SSc with normal routine cardiac evaluation, presenting either as myocardial inflammation or as severe reduction of MPRI and diffuse fibrosis with further deterioration in the long term follow up. PMID- 26374222 TI - Pathology of Struma Ovarii: A Report of 96 Cases. AB - Thyroid tissue is a relatively frequent component of mature teratoma and can occur in 5-20 % of cases. Struma ovarii is defined as ovarian goiter which comprises either entirely or predominantly thyroid tissue (>50 %). This also includes cases of mature teratoma with less than 50 % thyroid tissue but harboring thyroid-associated malignancy. A total of 118 patients with mature teratoma containing thyroid tissue were identified at our institution (1989 to 2014). Ninety-six cases were diagnosed struma ovarii, including 10 cases of papillary thyroid carcinoma, 1 case of highly differentiated follicular carcinoma of ovarian origin (HDFCO), 5 cases of strumal carcinoid, and 80 cases of struma ovarii (53 cases of thyroid-only struma ovarii). Six cases had diffuse adenomatous hyperplasia, and seven cases had focal adenomatous hyperplasia. There was no recurrence on follow-up except one of the papillary thyroid carcinomas. Concurrent primary ovarian lesions included: serous cystadenoma--3, mucinous cystadenoma--4, Brenner tumor--3, thecoma--2, ovarian fibroma--1, and focal hilus cell hyperplasia--4 cases. In this series, papillary thyroid carcinoma and strumal carcinoid were the most common well-differentiated neoplasm/malignancies arising in struma ovarii; these demonstrate a minimal or no aggressive clinical behavior. PMID- 26374224 TI - Outcomes of Complete Versus Partial Surgical Stabilization of Flail Chest. AB - BACKGROUND: Rib fractures are common after chest wall trauma. For patients with flail chest, surgical stabilization is a promising technique for reducing morbidity. Anatomical difficulties often lead to an inability to completely repair the flail chest; thus, the result is partial flail chest stabilization (PFS). We hypothesized that patients with PFS have outcomes similar to those undergoing complete flail chest stabilization (CFS). METHODS: A prospectively collected database of all patients who underwent rib fracture stabilization procedures from August 2009 until February 2013 was reviewed. Abstracted data included procedural and complication data, extent of stabilization, and pulmonary function test results. RESULTS: Of 43 patients who underwent operative stabilization of flail chest, 23 (53%) had CFS and 20 (47%) underwent PFS. Anterior location of the fracture was the most common reason for PFS (45%). Age, sex, operative time, pneumonia, intensive care unit and hospital length of stay, and narcotic use were the same in both groups. Total lung capacity was significantly improved in the CFS group at 3 months. No chest wall deformity was appreciated on follow-up, and no patients underwent additional stabilization procedures following PFS. CONCLUSION: Despite advances in surgical technique, not all fractures are amenable to repair. There was no difference in chest wall deformity, narcotic use, or clinically significant impairment in pulmonary function tests among patients who underwent PFS compared with CFS. Our data suggest that PFS is an acceptable strategy and that extending or creating additional incisions for CFS is unnecessary. PMID- 26374226 TI - The Role of the Interdomain Interactions on RfaH Dynamics and Conformational Transformation. AB - The transcription antiterminator RfaH has been shown to undergo major structural rearrangements to perform multiple functions. Structural determination of the C terminal domain (CTD) of RfaH showed that it can exist as either an alpha-helix bundle when interfacing with the N-terminal domain (NTD) or as a beta-barrel conformation when it is not interfacing with the NTD. In this paper, we investigate the full RfaH with both CTD and NTD using a variety of all-atom molecular dynamics (MD) simulation techniques, including targeted molecular dynamics, steered molecular dynamics, and adaptive biasing force, and calculate potentials of mean force. We also use network analysis to determine communities of amino acids that are important in transferring information about structural changes. We find that the CTD-NTD interdomain interactions constitute the main barrier in the CTD alpha-helix to beta-barrel structural conversion. Once the interfacial interactions are broken, the structural conversion of the CTD is relatively easy. We determined which amino acids play especially important roles in controlling the interdomain motions and also describe subtle structural changes that may be important in the functioning of RfaH. PMID- 26374227 TI - One Session Treatment for Specific Phobias: An Adaptation for Paediatric Blood Injection-Injury Phobia in Youth. AB - Blood-injection-injury (BII) phobia is a chronic and debilitating disorder, which has largely been neglected in the child literature. The present paper briefly reviews the aetiology of specific phobias with particular attention to BII and provides an integrated developmental model of this disorder in youth. Evidence based treatments for child-specific phobias are discussed, and the development of a modified one session treatment (OST) approach to enhance treatment outcomes for BII phobia in children and adolescents is described. This approach is illustrated in two children with a primary diagnosis of BII phobia. The cases illustrate the unique challenges associated with treating BII in youth and the need for a modified intervention. Modifications included addressing the role of pain (e.g., psychoeducation, more graduated exposure steps) and disgust (e.g., disgust eliciting exposure tasks) in the expression of the phobia and fainting in the maintenance of this phobia. Moreover, it is recommended that parents be more actively involved throughout treatment (e.g., education session prior to OST, contingency management training, guidance regarding planning exposure tasks following treatment) and for families to participate in a structured e-therapy maintenance programme post-treatment. PMID- 26374228 TI - Protective Mechanisms for Depression among Racial/Ethnic Minority Youth: Empirical Findings, Issues, and Recommendations. AB - We (1) review empirical studies that report findings regarding putative protective mechanisms when exposed to risk of depression in African American and Hispanic adolescents; (2) identify key protective mechanisms for different risk contexts that garner empirical support; (3) synthesize the mechanisms identified as protective against depression among racial/ethnic minority adolescents; and (4) discuss improved methods for advancing understanding of resilience against depression in minority youth. The studies were selected from PsycINFO searches that met the following inclusion criteria: participants between 12 and 21 years of age, inclusions of racial/ethnic minority members, examining protection through an interaction with a risk factor, and outcome measures of depression, depressed mood, or depressive symptomatology. We found 39 eligible studies; 13 of which included multiple racial/ethnic groups. The following were supported as protective mechanisms, at least preliminarily, for at least one racial/ethnic group and in at least one risk context: employment, extracurricular activities, father-adolescent closeness, familism, maternal support, attending predominately minority schools, neighborhood composition, non-parent support, parental inductive reasoning, religiosity, self-esteem, social activities, and positive early teacher relationships. To investigate protective mechanisms more comprehensively and accurately across individual, social, and community levels of influence, we recommend incorporating multilevel modeling or multilevel growth curve analyses and large diverse samples. PMID- 26374229 TI - Laser Ablation with Vacuum Capture for MALDI Mass Spectrometry of Tissue. AB - We have developed a laser ablation sampling technique for matrix-assisted laser desorption ionization (MALDI) mass spectrometry and tandem mass spectrometry (MS/MS) analyses of in-situ digested tissue proteins. Infrared laser ablation was used to remove biomolecules from tissue sections for collection by vacuum capture and analysis by MALDI. Ablation and transfer of compounds from tissue removes biomolecules from the tissue and allows further analysis of the collected material to facilitate their identification. Laser ablated material was captured in a vacuum aspirated pipette-tip packed with C18 stationary phase and the captured material was dissolved, eluted, and analyzed by MALDI. Rat brain and lung tissue sections 10 MUm thick were processed by in-situ trypsin digestion after lipid and salt removal. The tryptic peptides were ablated with a focused mid-infrared laser, vacuum captured, and eluted with an acetonitrile/water mixture. Eluted components were deposited on a MALDI target and mixed with matrix for mass spectrometry analysis. Initial experiments were conducted with peptide and protein standards for evaluation of transfer efficiency: a transfer efficiency of 16% was obtained using seven different standards. Laser ablation vacuum capture was applied to freshly digested tissue sections and compared with sections processed with conventional MALDI imaging. A greater signal intensity and lower background was observed in comparison with the conventional MALDI analysis. Tandem time-of-flight MALDI mass spectrometry was used for compound identification in the tissue. PMID- 26374232 TI - Population Level Purifying Selection and Gene Expression Shape Subgenome Evolution in Maize. AB - The maize ancestor experienced a recent whole-genome duplication (WGD) followed by gene erosion which generated two subgenomes, the dominant subgenome (maize1) experiencing fewer deletions than maize2. We take advantage of available extensive polymorphism and gene expression data in maize to study purifying selection and gene expression divergence between WGD retained paralog pairs. We first report a strong correlation in nucleotide diversity between duplicate pairs, except for upstream regions. We then show that maize1 genes are under stronger purifying selection than maize2. WGD retained genes have higher gene dosage and biased Gene Ontologies consistent with previous studies. The relative gene expression of paralogs across tissues demonstrates that 98% of duplicate pairs have either subfunctionalized in a tissuewise manner or have diverged consistently in their expression thereby preventing functional complementation. Tissuewise subfunctionalization seems to be a hallmark of transcription factors, whereas consistent repression occurs for macromolecular complexes. We show that dominant gene expression is a strong determinant of the strength of purifying selection, explaining the inferred stronger negative selection on maize1 genes. We propose a novel expression-based classification of duplicates which is more robust to explain observed polymorphism patterns than the subgenome location. Finally, upstream regions of repressed genes exhibit an enrichment in transposable elements which indicates a possible mechanism for expression divergence. PMID- 26374231 TI - COSMOS--improving the quality of life in nursing home patients: protocol for an effectiveness-implementation cluster randomized clinical hybrid trial. AB - BACKGROUND: Nursing home patients have complex mental and physical health problems, disabilities and social needs, combined with widespread prescription of psychotropic drugs. Preservation of their quality of life is an important goal. This can only be achieved within nursing homes that offer competent clinical conditions of treatment and care. COmmunication, Systematic assessment and treatment of pain, Medication review, Occupational therapy, Safety (COSMOS) is an effectiveness-implementation hybrid trial that combines and implements organization of activities evidence-based interventions to improve staff competence and thereby the patients' quality of life, mental health and safety. The aim of this paper is to describe the development, content and implementation process of the COSMOS trial. METHODS/DESIGN: COSMOS includes a 2-month pilot study with 128 participants distributed among nine Norwegian nursing homes, and a 4-month multicenter, cluster randomized effectiveness-implementation clinical hybrid trial with follow-up at month 9, including 571 patients from 67 nursing home units (one unit defined as one cluster). Clusters are randomized to COSMOS intervention or current best practice (control group). The intervention group will receive a 2-day education program including written guidelines, repeated theoretical and practical training (credited education of caregivers, physicians and nursing home managers), case discussions and role play. The 1-day midway evaluation, information and interviews of nursing staff and a telephone hotline all support the implementation process. Outcome measures include quality of life in late-stage dementia, neuropsychiatric symptoms, activities of daily living, pain, depression, sleep, medication, cost-utility analysis, hospital admission and mortality. DISCUSSION: Despite complex medical and psychosocial challenges, nursing home patients are often treated by staff possessing low level skills, lacking education and in facilities with a high staff turnover. Implementation of a research-based multicomponent intervention may improve staff's knowledge and competence and consequently the quality of life of nursing home patients in general and people with dementia in particular. TRIAL REGISTRATION: ClinicalTrials.gov NCT02238652. PMID- 26374233 TI - Depression, anxiety and cognitive function in patients with type 2 diabetes: an 8 year prospective observational study. AB - AIMS: Since depression, anxiety and cognitive function may be impaired in type 2 diabetes, we investigated the relationships between clinical and socioeconomic variables and these psychological dimensions. METHODS: For an 8-year prospective observational study of 498 patients, 249 were not insulin-treated (NIT) and 249 were insulin-treated (IT). Demographic, socioeconomic and clinical data were monitored along with depression and anxiety (assessed by Zung questionnaire) and cognitive function by Mini Mental State Examination (MMSE). RESULTS: After 8 years, 131 patients remained NIT (NIT-NIT), 179 remained IT (IT-IT), 47 switched to insulin (NIT-IT), 111 were lost to follow-up and 30 were died. In all groups, HbA1c remained stable, BMI, glucose and lipid profile improved, and foot ulcers and retinopathy worsened. Mild worsening in depression and anxiety scores was observed in the IT-IT patients only. On multivariate analysis, worsening of depression was associated with female gender, disease duration and being IT-IT, and worsening of anxiety with disease duration. Decreased MMSE was associated inversely with smoking and directly with being IT-IT. CONCLUSIONS: Patients with type 2 diabetes are at relatively low risk of psycho-cognitive decline. However, being female and on long-term insulin treatment may be risk factors for psychological distress, suggesting that special attention is required for these patients. PMID- 26374234 TI - Motor development in children prenatally exposed to selective serotonin reuptake inhibitors: a large population-based pregnancy cohort study. AB - OBJECTIVES: To estimate the association between prenatal exposure to selective serotonin reuptake inhibitors (SSRIs) and motor development in children considering the effect of maternal symptoms of anxiety and depression before, during and after pregnancy. DESIGN: Population-based prospective pregnancy cohort study. SETTING: The Norwegian Mother and Child Cohort study (MoBa) (1999-2008). POPULATION: A total of 51 404 singleton pregnancies. METHODS: Self-reported use of SSRIs was collected for the 6 months before pregnancy and prospectively during pregnancy. We used ordinal logistic regression as the statistical analysis. MAIN OUTCOME MEASURES: Motor development was assessed by maternal reports of fine and gross motor development at child age 3 years by items from the Ages and Stages Questionnaire (ASQ). The maternal ASQ scores were compared with data from a MoBa sub-study where clinicians assessed motor development with the Gross and Fine Motor Mullen scales of early learning. RESULTS: In all 381 women (0.7%) reported use of SSRIs during pregnancy, of these 159 reported on at least two questionnaires (prolonged use). Prolonged SSRI exposure was associated with a delay in fine motor development, odds ratio 1.42 (95% CI 1.07-1.87) compared with no SSRI exposure, after adjusting for symptoms of anxiety and depression before and during pregnancy. Severity of maternal depression seemed to explain the association only partially. Stratifying on depression after pregnancy had no impact on the estimated effect of SSRIs. CONCLUSIONS: Prolonged prenatal exposure to SSRIs was weakly associated with a delayed motor development at age 3 years, but not to the extent that the delay was of clinical importance. TWEETABLE ABSTRACT: Long-term prenatal SSRI exposure is weakly associated with delayed motor development independent of depression. PMID- 26374235 TI - Bordetella pertussis transmission. AB - Bordetella pertussis and B. bronchiseptica are Gram-negative bacterial respiratory pathogens. Bordetella pertussis is the causative agent of whooping cough and is considered a human-adapted variant of B. bronchiseptica. Bordetella pertussis and B. bronchiseptica share mechanisms of pathogenesis and are genetically closely related. However, despite the close genetic relatedness, these Bordetella species differ in several classic fundamental aspects of bacterial pathogens such as host range, pathologies and persistence. The development of the baboon model for the study of B. pertussis transmission, along with the development of the swine and mouse model for the study of B. bronchiseptica, has enabled the investigation of different aspects of transmission including the route, attack rate, role of bacterial and host factors, and the impact of vaccination on transmission. This review will focus on B. pertussis transmission and how animal models of B. pertussis transmission and transmission models using the closely related B. bronchiseptica have increased our understanding of B. pertussis transmission. PMID- 26374236 TI - Is there more than one way to skin a newt? Convergent toxin resistance in snakes is not due to a common genetic mechanism. AB - Convergent evolution of tetrodotoxin (TTX) resistance, at both the phenotypic and genetic levels, characterizes coevolutionary arms races between amphibians and their snake predators around the world, and reveals remarkable predictability in the process of adaptation. Here we examine the repeatability of the evolution of TTX resistance in an undescribed predator-prey relationship between TTX-bearing Eastern Newts (Notophthalmus viridescens) and Eastern Hog-nosed Snakes (Heterodon platirhinos). We found that that local newts contain levels of TTX dangerous enough to dissuade most predators, and that Eastern Hog-nosed Snakes within newt range are highly resistant to TTX. In fact, these populations of Eastern Hog nosed Snakes are so resistant to TTX that the potential for current reciprocal selection might be limited. Unlike all other cases of TTX resistance in vertebrates, H. platirhinos lacks the adaptive amino acid substitutions in the skeletal muscle sodium channel that reduce TTX binding, suggesting that physiological resistance in Eastern Hog-nosed Snakes is conferred by an alternate genetic mechanism. Thus, phenotypic convergence in this case is not due to parallel molecular evolution, indicating that there may be more than one way for this adaptation to arise, even among closely related species. PMID- 26374237 TI - A novel landscape genetic approach demonstrates the effects of human disturbance on the Udzungwa red colobus monkey (Procolobus gordonorum). AB - A comprehensive understanding of how human disturbance affects tropical forest ecosystems is critical for the mitigation of future losses in global biodiversity. Although many genetic studies of tropical forest fragmentation have been conducted to provide insight into this issue, relatively few have incorporated landscape data to explicitly test the effects of human disturbance on genetic differentiation among populations. In this study, we use a newly developed landscape genetic approach that relies on a genetic algorithm to simultaneously optimize resistance surfaces to investigate the effects of human disturbance in the Udzungwa Mountains of Tanzania, which is an important part of a universally recognized biodiversity hotspot. Our study species is the endangered Udzungwa red colobus monkey (Procolobus gordonorum), which is endemic to the Udzungwa Mountains and a known indicator species that thrives in large and well-protected blocks of old growth forest. Population genetic analyses identified significant population structure among Udzungwa red colobus inhabiting different forest blocks, and Bayesian cluster analyses identified hierarchical structure. Our new method for creating composite landscape resistance models found that the combination of fire density on the landscape and distance to the nearest village best explains the genetic structure observed. These results demonstrate the effects that human activities are having in an area of high global conservation priority and suggest that this ecosystem is in a precarious state. Our study also illustrates the ability of our novel landscape genetic method to detect the impacts of relatively recent landscape features on a long lived species. PMID- 26374239 TI - Low-dimensional boron structures based on icosahedron B12. AB - One-dimensional icosahedral boron chains and two-dimensional icosahedral boron sheets (icosahedral alpha, delta6, and delta4 sheets) that contain icosahedra B12 as their building units have been predicted in a computer simulation study using a state-of-the-art semi-empirical Hamiltonian. These novel low-dimensional icosahedral structures exhibit interesting bonding and electronic properties. Specifically, the three-center, two-electron bonding between icosahedra B12 of the boron bulk (rhombohedral boron) transforms into a two-center bonding in these new allotropes of boron sheets. In contrast to the previously reported stable buckled alpha and triangular boron monolayer sheets, these new allotropes of boron sheets form a planar network. Calculations of electronic density of states (DOS) reveal a semiconducting nature for both the icosahedral chain and the icosahedral delta6 and delta4 sheets, as well as a nearly gapless (or metallic like) feature in the DOS for the icosahedral alpha sheet. The results for the energy barrier per atom between the icosahedral delta6 and alpha sheets (0.17 eV), the icosahedral delta6 and delta4 sheets (0.38 eV), and the icosahedral alpha and delta4 sheets (0.27 eV), as indicated in the respective parentheses, suggest that these new allotropes of boron sheets are relatively stable. PMID- 26374240 TI - The test-retest reliability of the Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF) for assessing type of urinary incontinence in males and females. PMID- 26374238 TI - High-density sex-specific linkage maps of a European tree frog (Hyla arborea) identify the sex chromosome without information on offspring sex. AB - Identifying homology between sex chromosomes of different species is essential to understanding the evolution of sex determination. Here, we show that the identity of a homomorphic sex chromosome pair can be established using a linkage map, without information on offspring sex. By comparing sex-specific maps of the European tree frog Hyla arborea, we find that the sex chromosome (linkage group 1) shows a threefold difference in marker number between the male and female maps. In contrast, the number of markers on each autosome is similar between the two maps. We also find strongly conserved synteny between H. arborea and Xenopus tropicalis across 200 million years of evolution, suggesting that the rate of chromosomal rearrangement in anurans is low. Finally, we show that recombination in males is greatly reduced at the centers of large chromosomes, consistent with previous cytogenetic findings. Our research shows the importance of high-density linkage maps for studies of recombination, chromosomal rearrangement and the genetic architecture of ecologically or economically important traits. PMID- 26374241 TI - Microaggressions, Feelings of Difference, and Resilience Among Adopted Children with Sexual Minority Parents. AB - Limited research exists about the unique experiences and possible marginalization of children with sexual minority parents. From a larger longitudinal project of diverse adoptive families, we examined cross-sectional data using mixed methods from interviews with 49 adopted children (M age = 8 years; 47% female) in 27 two father and 22 two-mother families. Using thematic analysis, we coded themes of awareness of difference, microaggressions, and resilience (i.e., coping and positive family conceptualizations). Children experienced "feeling different" and microaggressions from peers, but generally at a low to medium intensity and with neutral (not negative) emotion. More instances of resilience and positive family conceptualizations were reported than microaggressions or feelings of difference, suggesting that children develop positive perceptions of their family and navigate experiences of difference with resilience. Filling important gaps in the literature, we discuss implications of our results for practice and policy. PMID- 26374242 TI - Intrahepatic cholangiocarcinoma and gallbladder cancer: distinguishing molecular profiles to guide potential therapy. AB - BACKGROUND: Chemotherapy regimens for intrahepatic cholangiocarcinoma (ICC) and gallbladder adenocarcinoma (GC) remain interchangeable; however, response rates are frequently suboptimal. Biomarkers from ICC and GC patients were interrogated to identify actionable differences with potential therapeutic implications. METHODS: From 2009 to 2012, pathological specimens from 217 ICC and 28 GC patients referred to Caris Life Sciences were evaluated. Specific testing by immunohistochemical analysis for 17 different biomarkers was performed. RESULTS: In the collective cohort (n = 245), actionable targets included: 95% low thymidylate synthase (TS), 82% low ribonucleotide reductase subunit M (RMM) 1 and 74% low excision repair cross complementation group (ERCC) 1, indicating potential susceptibility to fluoropyrimidines/capecitabine, gemcitabine and platinum agents, respectively. Additional targets included TOPO1 (53.3% high, Irinotecan), MGMT (50.3% low, temozolomide), TOP2A (33% high, anthracyclines) and PGP (30.1% low, taxanes). Subgroup analysis by tumour origin demonstrated a differential biomarker expression pattern with a higher frequency of ICC tumours showing low levels of TS (99% versus 72%, P < 0.01), and RRM1 (85% versus 64%, P = 0.02) when compared with GC. Conversely a greater frequency of GC demonstrated high levels of TOPO1 (76% versus 50%, P = 0.02) versus ICC, indicating a potential increased benefit from irinotecan. DISCUSSION: Differences in the molecular profiles between ICC and GC provide evidence that the two are distinct diseases, requiring different treatment strategies to optimize a response. PMID- 26374243 TI - Imaging Approach to Temporomandibular Joint Disorders. AB - Internal derangement is the most common temporomandibular joint disorder. Degenerative osteoarthritis and trauma are next in frequency. Less common pathology includes rheumatoid arthritis, synovial chondromatosis, calcium pyrophosphate dehydrate deposition disease, pigmented villonodular synovitis, tumors, infection, and osteonecrosis. We provide a systematic approach to facilitate interpretation based on major anatomic structures: disc-attachments, joint space, condyle, and lateral pterygoid muscle. Relevant graphic anatomy and state of the art imaging are discussed in correlation with current clinical and therapeutic highlights of pathologic entities affecting the joint. PMID- 26374244 TI - Flavobacterium buctense sp. nov., isolated from freshwater. AB - A gram-negative, non-gliding motile, aerobic bacterium, designated as strain T7(T), was isolated from freshwater of Chishui River flowing through Maotai town, Guizhou Province, southwest of China. Based on the 16S rRNA gene sequence analysis, the isolate was identified as a member of the genus Flavobacterium and that shared less than 97 % sequence similarities with recognized Flavobacterium species. Its closest phylogenetic relative was Flavobacterium dankookense (96.9 %), followed by Flavobacterium cheonhonense (96.8 %) and Flavobacterium macrobrachii (96.7 %). The strain formed smooth yellow colonies on R2A plates, and cells were observed to be short rods. Strain T7(T) was found to be able to grow at 15-30 degrees C (optimum 25 degrees C), at NaCl concentration of 0-0.5 % (optimum 0 %) and at pH 6.5-9.5 (optimum pH 7.5). Catalase and oxidase tests were positive. Polar lipids of strain T7(T) included phosphatidylethanolamine, four unidentified polar lipids, one unidentified phospholipid and one unidentified aminolipid. Chemotaxonomic analysis revealed menaquinone-6 as the dominant respiratory quinone and C(15:0), iso-C(15:0) and iso-C(15:1) as the major fatty acids. The DNA G+C content of strain T7(T) was determined to be 38.2 mol%. On the basis of phylogenetic, phenotypic and genetic data obtained in this study, strain T7(T) represents a novel species of the genus Flavobacterium, for which the name Flavobacterium buctense sp. nov. is proposed. The type strain is T7(T) (=JCM 30750=CGMCC 1.15216). PMID- 26374245 TI - Branched-chain amino acid supplementation promotes aerobic growth of Salmonella Typhimurium under nitrosative stress conditions. AB - Nitric oxide (NO) inactivates iron-sulfur enzymes in bacterial amino acid biosynthetic pathways, causing amino acid auxotrophy. We demonstrate that exogenous supplementation with branched-chain amino acids (BCAA) can restore the NO resistance of hmp mutant Salmonella Typhimurium lacking principal NO metabolizing enzyme flavohemoglobin, and of mutants further lacking iron-sulfur enzymes dihydroxy-acid dehydratase (IlvD) and isopropylmalate isomerase (LeuCD) that are essential for BCAA biosynthesis, in an oxygen-dependent manner. BCAA supplementation did not affect the NO consumption rate of S. Typhimurium, suggesting the BCAA-promoted NO resistance independent of NO metabolism. BCAA supplementation also induced intracellular survival of ilvD and leuCD mutants at wild-type levels inside RAW 264.7 macrophages that produce constant amounts of NO regardless of varied supplemental BCAA concentrations. Our results suggest that the NO-induced BCAA auxotrophy of Salmonella, due to inactivation of iron-sulfur enzymes for BCAA biosynthesis, could be rescued by bacterial taking up exogenous BCAA available in oxic environments. PMID- 26374247 TI - Enzymatic synthesis of novel isobavachalcone glucosides via a UDP glycosyltransferase. AB - Glycosylation is often used to improve a natural product's properties such as water solubility, chemical stability, pharmacological potency, and structure diversification. In this study, we studied the enzymatic synthesis of novel isobavachalcone glucosides using a UDP-glycosyltransferase (YjiC) from Bacillus licheniformis DSM-13. The chemical structures of compounds 1 and 2 were elucidated by spectroscopic techniques, including LC-MS, MS, and NMR. Meanwhile, the parameters of glycosylation reaction such as incubation time, UDP-glucose concentration, and pH of buffer were also optimized during this study. Furthermore, the compounds 1 and 2 exhibited weak anti-proliferative activities against five human cancer cell lines, with IC50 values ranging from 58.6 to 86.6 MUM. PMID- 26374246 TI - Evaluating the role of phage-shock protein A in Burkholderia pseudomallei. AB - The phage-shock protein (Psp) response is an extracytoplasmic response system that is vital for maintenance of the cytoplasmic membrane when the cell encounters stressful conditions. The paradigm of the Psp response has been established in Escherichia coli. The response has been shown to be important for survival during the stationary phase, maintenance of the proton motive force across membranes and implicated in virulence. In this study, we identified a putative PspA homologue in Burkholderia pseudomallei, annotated as BPSL2105. Similar to the induction of PspA in E. coli, the expression of B. pseudomallei BPSL2105 was induced by heat shock. Deletion of BPSL2105 resulted in a survival defect in the late stationary phase coincident with dramatic changes in the pH of the culture medium. The B. pseudomallei BPSL2105 deletion mutant also displayed reduced survival in macrophage infection - the first indication that the Psp response plays a role during intracellular pathogenesis in this species. The purified protein formed large oligomeric structures similar to those observed for the PspA protein of E. coli, and PspA homologues in Bacillus, cyanobacteria and higher plants, providing further evidence to support the identification of BPSL2105 as a PspA-like protein in B. pseudomallei. PMID- 26374249 TI - Low temperature hydrothermal synthesis, structure and magnetic properties of RECrO3 (RE = La, Pr, Nd, Sm). AB - Perovskite structured rare-earth chromites (RECrO3) are an interesting family of functional materials due to their wide application in numerous areas. Various methods have been used to synthesize this family of materials; however, such methods usually need a high temperature crystallization process above 800 degrees C, and only produce polycrystalline ceramics. Herein, a series of RECrO3 single crystal samples with uniform particle sizes were prepared via a mild hydrothermal method with temperatures as low as 240-260 degrees C, and the synthesis conditions were studied in detail. Samples of LaCrO3, PrCrO3, and NdCrO3 were indexed to the Pnma space group, whereas SmCrO3 was indexed to Pbnm. The shapes of the crystals changed from cubic to plate as a result of the crystal lattice distortions induced by the reduction in the size of the A-site rare-earth cation. Raman spectra of the samples showed characteristic vibration modes of CrO6 clusters. Temperature dependent magnetization studies showed a transition from antiferromagnetism to paramagnetism in all the samples. Higher maximum and residual magnetization was achieved in all the hydrothermally prepared samples compared with those prepared by other methods. PMID- 26374248 TI - New neo-lignan from Acanthopanax senticosus with protein tyrosine phosphatase 1B inhibitory activity. AB - New neo-lignan, (7S, 8R)-3-hydroxyl-4-methoxyl-balanophonin (1), together with seven known compounds (2-8) were isolated from the EtOAc-soluble extract of Acanthopanax senticosus. The structure of the new neo-lignan was elucidated with spectroscopic and physico-chemical analyses. All the isolates were evaluated for in vitro inhibitory activity against PTP1B, VHR and PP1. Among them, the new compound (1) was found to exhibit selective inhibitory activity on PTP1B with IC50 value 15.2 +/- 1.4 uM. PMID- 26374250 TI - Chronic underfunding in palliative care is key cause of poor care of dying people. PMID- 26374251 TI - High-field FTICR-MS data evaluation of natural organic matter: are CHON5S2 molecular class formulas assigned to (13)C isotopic m/z and in reality CHO components? AB - The analysis of dissolved organic matter (DOM) using high-field Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) poses challenges in molecular formula assignment. The consideration of (13)C isotopes provides new insights into the consistent elemental formula solutions. Modern software helps to overcome misinterpretation, but false assignments of molecular classes to mass peaks have rarely been elucidated until now. It will be demonstrated that this can be important with formula assignments comprising exactly five nitrogen and two sulfur atoms in DOM data sets: the molecular class CHON5S2. The existence of such components in DOM under tripeptide Met-His-Cys formed with the formula C14H23O4N5S2 cannot be excluded; however, components containing 5 N and 2 S should be suspected to not be highly abundant. The true elemental compositions of such unusual "N5S2 moieties" were calculated using Suwannee River fulvic acid (SRFA) data from the literature and one data set from acidic pit lake pore water. The replacement of a H3N5S2 moiety with a (13)C1(12)C5O4 moiety explained more than 95% of the questionable "N5S2 moieties". This finding was proved by calculation of delta(13)C0/00 values from relative peak intensities. PMID- 26374253 TI - Aseptic Raman spectroscopy can detect changes associated with the culture of human dental pulp stromal cells in osteoinductive culture. AB - There is an unmet need for the non-invasive characterisation of stem cells to facilitate the translation of cell-based therapies. Raman spectroscopy has proven utility in stem cell characterisation but as yet no method has been reported capable of taking repeated Raman measurements of living cells aseptically over time. The aim of this study was to determine if Raman spectroscopy could be used to monitor changes in a well characterised cell population (human dental pulp stromal cells (DPSCs)) by taking repeated Raman measurements from the same cell populations in osteoinductive culture over time and under aseptic conditions. DPSCs were isolated from extracted premolar teeth from 3 consenting donors. Following in vitro expansion, DPSCs were maintained for 28 days in osteo inductive medium. Raman spectra were acquired from the cells at days 0, 3, 7, 10, 14 and 28. Principal component analysis (PCA) was carried out to assess if there was any temporal spectral variation. At day 28, osteoinduction was confirmed using alizarin red staining and qRT-PCR for alkaline phosphatase and osteocalcin. Alizarin red staining was positive in all samples at day 28 and significant increases in alkaline phosphatase (p < 0.001) and osteocalcin (p < 0.05) gene expression were also observed compared with day 0. PCA of the Raman data demonstrated trends in PC1 from days 0-10, influenced by protein associated features and PC2 from days 10-28, influenced by DNA/RNA associated features. We conclude that spectroscopy can be used to monitor changes in Raman signature with time associated with the osteoinduction of DPSCs using repeated measurements via an aseptic methodology. PMID- 26374254 TI - Anion-Tunable Properties and Electrochemical Performance of Functionalized Ferrocene Compounds. AB - We report a series of ionically modified ferrocene compounds for hybrid lithium organic non-aqueous redox flow batteries, based on the ferrocene/ferrocenium redox couple as the active catholyte material. Tetraalkylammonium ionic moieties were incorporated into the ferrocene structure, in order to enhance the solubility of the otherwise relatively insoluble ferrocene. The effect of various counter anions of the tetraalkylammonium ionized species appended to the ferrocene, such as bis(trifluoromethanesulfonyl)imide, hexafluorophosphate, perchlorate, tetrafluoroborate, and dicyanamide on the solubility of the ferrocene was investigated. The solution chemistry of the ferrocene species was studied, in order to understand the mechanism of solubility enhancement. Finally, the electrochemical performance of these ionized ferrocene species was evaluated and shown to have excellent cell efficiency and superior cycling stability. PMID- 26374255 TI - To chew or not to chew: that's the question. AB - A 25-year-old Somalian man was referred to the department of internal medicine because of nausea, vomiting and jaundice of recent onset. On physical examination, he was frankly icteric without clinical signs of chronic liver disease. Laboratory data showed evidence of acute hepatitis. Viral serologic tests for hepatitis A, B, C and E were negative. Antinuclear antibodies (ANA) were positive (titre 1 : 1280; speckled pattern, NV < 1 : 40) as well anti-actin antibodies (titre 75 UA, NV < 20). A liver biopsy was performed and showed a feature compatible with toxic hepatitis. On further questioning, the patient admitted to daily chew Khat when he was living in Somalia. We concluded to Khat induced toxic hepatitis together with high-titre anti-nuclear antibody mimicking serologic patterns of auto-immune hepatitis. PMID- 26374256 TI - Nonlinear spin-wave excitations at low magnetic bias fields. AB - Nonlinear magnetization dynamics is essential for the operation of numerous spintronic devices ranging from magnetic memory to spin torque microwave generators. Examples are microwave-assisted switching of magnetic structures and the generation of spin currents at low bias fields by high-amplitude ferromagnetic resonance. Here we use X-ray magnetic circular dichroism to determine the number density of excited magnons in magnetically soft Ni80Fe20 thin films. Our data show that the common model of nonlinear ferromagnetic resonance is not adequate for the description of the nonlinear behaviour in the low magnetic field limit. Here we derive a model of parametric spin-wave excitation, which correctly predicts nonlinear threshold amplitudes and decay rates at high and at low magnetic bias fields. In fact, a series of critical spin wave modes with fast oscillations of the amplitude and phase is found, generalizing the theory of parametric spin-wave excitation to large modulation amplitudes. PMID- 26374257 TI - Editorial: towards extended acid suppression--the search continues. PMID- 26374258 TI - Letter: faecal microbiota transplantation in combination with fidaxomicin to treat severe complicated recurrent Clostridium difficile infection. PMID- 26374259 TI - Letter: faecal microbiota transplantation in combination with fidaxomicin to treat severe complicated recurrent Clostridium difficile infection--authors' reply. PMID- 26374260 TI - Letter: anti-CTLA-4-associated colitis and inflammatory bowel disease pathogenesis. PMID- 26374261 TI - Letter: anti-CTLA-4-associated colitis and inflammatory bowel disease pathogenesis--authors' reply. PMID- 26374262 TI - Letter: the response to somatostatin analogues in neuroendocrine tumours is influenced by the Ki67 score. PMID- 26374263 TI - Letter: the response to somatostatin analogues in neuroendocrine tumours is influenced by Ki67 score--authors' reply. PMID- 26374264 TI - New Dual Fluorescent Probe for Simultaneous Biothiol and Phosphate Bioimaging. AB - The simultaneous detection of relevant metabolites in living organisms by using one molecule introduces an approach to understanding the relationships between these metabolites in healthy and deregulated cells. Fluorescent probes of low toxicity are remarkable tools for this type of analysis of biological systems in vivo. As a proof of concept, different naturally occurring compounds, such as biothiols and phosphate anions, were the focus for this work. The 2,4 dinitrobenzenesulfinate (DNBS) derivative of 9-[1-(4-tert-butyl-2-methoxyphenyl)] 6-hydroxy-3H-xanthen-3-one (Granada Green; GG) were designed and synthesized. This new sulfinyl xanthene derivative can act as a dual sensor for the aforementioned analytes simultaneously. The mechanism of action of this derivative implies thiolysis of the sulfinyl group of the weakly fluorescent DNBS GG by biological thiols at near-neutral pH values, thus releasing the fluorescent GG moiety, which simultaneously responds to phosphate anions through its fluorescence-decay time. The new dual probe was tested in solution by using steady-state and time-resolved fluorescence and intracellularly by using fluorescence-lifetime imaging microscopy (FLIM) in human epithelioid cervix carcinoma (HeLa) cells. PMID- 26374265 TI - Norovirus diversity in children with gastroenteritis in South Africa from 2009 to 2013: GII.4 variants and recombinant strains predominate. AB - From 2009 to 2013 the diversity of noroviruses (NoVs) in children (?5 years) hospitalized with gastroenteritis in South Africa was investigated. NoVs were genotyped based on nucleotide sequence analyses of partial RNA-dependent RNA polymerase (RdRp) and capsid genes. Seventeen RdRp genotypes (GI.P2, GI.P3, GI.P6, GI.P7, GI.P not assigned (NA), GI.Pb, GI.Pf, GII.P2, GII.P4, GII.P7, GII.P13, GII.P16, GII.P21, GII.Pc, GII.Pe, GII.Pg, GII.PNA) and 20 capsid genotypes (GI.1, GI.2, GI.3, GI.5, GI.6, GI.7, GI.NA, GII.1, GII.2, GII.3, GII.4, GII.6, GII.7, GII.10, GII.12, GII.13, GII.14, GII.16, GII.17, GII.21) were identified. The combined RdRp/capsid genotype was determined for 275 GII strains. Fifteen confirmed recombinant NoV strains circulated during the study period. NoV GII.P4/GII.4 (47%) and GII.Pe/GII.4 (18%) predominated, followed by GII.PNA/GII.3 (10%) and GII.P21/GII.3 (7%). Other prevalent strains included GII.Pg/GII.12 (6%) and GII.Pg/GII.1 (3%). Two novel recombinants, GII.Pg/GII.2 and GII.Pg/GII.10 were identified. In 2013 the replacement of GII.4 New Orleans 2009 and GII.P21/GII.3, which predominated during the early part of the study, with GII.4 Sydney 2012 and GII.PNA/GII.3 was observed. This study presents the most comprehensive recent data on NoV diversity in Africa. PMID- 26374266 TI - The surgical management of hypertrophic obstructive cardiomyopathy with the concomitant mitral valve abnormalities. AB - OBJECTIVES: The purpose of this retrospective study was to analyse the pathogenesis and the treatment strategies of hypertrophic obstructive cardiomyopathy (HOCM) with the concomitant mitral valve abnormalities. METHODS: Between October 1996 and December 2009, 76 patients with the HOCM underwent the ventricular septal myotomy-myectomy in Fuwai hospital. There were 51 males and 25 females aged between 6 and 68 years (mean: 37.18 +/- 15.85 years) old. All the patients had left ventricular outflow tract (LVOT) obstruction with a resting or physically provoked gradient of >=50 mmHg and the systolic anterior movement (SAM) of the mitral leaflets, and 64 patients had mitral regurgitation (MR). These patients underwent the ventricular septal myotomy-myectomy under general anaesthesia and cardiopulmonary bypass. The concomitant surgical procedures included mitral valve replacement (MVR, n = 14) and mitral valve plasty (MVP, n = 12). RESULTS: All the surgical procedures were technically successful. In comparison with the preoperative conditions, the resting LVOT gradient had marked reduction (99.73 +/- 38.61-23.55 +/- 16.53 mmHg, P < 0.001), the mean septal thickness was decreased from 26.23 +/- 5.24 to 17.33 +/- 4.74 mm. MR had significant improvement, SAM was resolved completely or only mild. Four patients (5.3%, 4/76) died during the hospital stay. The causes of death included severe ventricular arrhythmias with low cardiac output, severe acute renal failure, septic shock with acute renal dysfunction and the complete AV block with low cardiac output. The others were followed up for 5-18 years: there were no deaths. Moderate MR was noted in two patients at 2 months or 2 years after operation respectively, who had undergone MVP with the edge-to-edge technique stitch procedure, and only had mild or trivial MR at hospital discharge, of whom one received repeat operation with MVR and the other is still in follow-up. All surviving patients were evaluated as New York Heart Association Functional class I or II, and had a significant increase in physical capacity and a significant reduction in disabling symptoms. CONCLUSIONS: The ventricular septal myotomy myectomy can be performed successfully for the severe obstructive HOCM and MR with the low morbidity and mortality and excellent survival in the great majority of patients. But for the few patients with the intrinsic mitral valve disease, the concomitant MVP or MVR may be required, and MVR should be performed only as a priority choice for the inherent risks of prosthetic valves and anticoagulation therapy. PMID- 26374268 TI - Full-arch implant fixed prostheses: a comparative study on the effect of connection type and impression technique on accuracy of fit. AB - PURPOSE: The aim of this study was to assess the effect of connection type and impression technique on the accuracy of fit of implant-supported fixed complete arch dental prostheses (IFCDPs). MATERIALS AND METHODS: An edentulous mandibular cast with five implants was fabricated to serve as master cast (control) for both implant- and abutment-level baselines. A titanium one-piece framework for an IFCDP was milled at abutment level and used for accuracy of fit measurements. Polyether impressions were made using a splinted and non-splinted technique at the implant and abutment level leading to four test groups, n = 10 each. Hence, four groups of test casts were generated. The impression accuracy was evaluated indirectly by assessing the fit of the IFCDP framework on the generated casts of the test groups, clinically and radiographically. Additionally, the control and all test casts were digitized with a high-resolution reference scanner (IScan D103i, Imetric, Courgenay, Switzerland) and standard tessellation language datasets were generated and superimposed. Potential correlations between the clinical accuracy of fit data and the data from the digital scanning were investigated. To compare the accuracy of casts of the test groups versus the control at the implant and abutment level, Fisher's exact test was used. RESULTS: Of the 10 casts of test group I (implant-level splint), all 10 presented with accurate clinical fit when the framework was seated on its respective cast, while only five of 10 casts of test group II (implant-level non-splint) showed adequate fit. All casts of group III (abutment-level splint) presented with accurate fit, whereas nine of 10 of the casts of test group IV (abutment-level non-splint) were accurate. Significant 3D deviations (P < 0.05) were found between group II and the control. No statistically significant differences were found between groups I, III, and IV compared with the control. Implant connection type (implant level vs. abutment level) and impression technique did affect the 3D accuracy of implant impressions only with the non-splint technique (P < 0.05). CONCLUSION: For one-piece IFCDPs, the implant-level splinted impression technique showed to be more accurate than the non-splinted approach, whereas at the abutment-level, no difference in the accuracy was found. PMID- 26374269 TI - Mild dehydration modifies the cerebrovascular response to the cold pressor test. AB - The cold pressor test (CPT) is widely used in clinical practice and physiological research. It is characterized by a robust autonomic response, with associated increases in heart rate (HR), mean arterial pressure (MAP) and mean middle cerebral artery blood flow velocity (MCAv(mean)). Hydration status is not commonly reported when conducting this test, yet blood viscosity alone can modulate MCAv(mean), potentially modifying the MCAv(mean) response to the CPT. We investigated the effect of mild dehydration on the physiological response to the CPT in 10 healthy men (mean +/- SD: age 28 +/- 5 years; body mass 83 +/- 5 kg). All participants completed two CPTs, cold water (0 degrees C) immersion of both feet for 90 s, with the order of the euhydration and dehydration trials counterbalanced. Beat-to-beat MCAv, MAP, HR and breath-by-breath partial pressure of end-tidal CO2 (P(ET,CO2)) were measured continuously. Participants' pain perception was measured 1 min into the CPT using a visual analog scale (no pain = 0; maximal pain = 10). Dehydration significantly elevated plasma osmolality and urine specific gravity and reduced body mass (all P < 0.01). The MAP and HR responses were not different between treatments (both P > 0.05). After 90 s of immersion, the change in MCAv(mean) from baseline was less in the dehydration compared with the euhydration trial (change 0 +/- 5 versus 7 +/- 7 cm s(-1), P = 0.01), as was P(ET,CO2) (change -3 +/- 2 versus 0 +/- 3 mmHg, P = 0.02). Dehydration was associated with greater relative pain sensation during the CPT (7.0 +/- 1.3 vs 5.8 +/- 1.8, P = 0.02). Our results demonstrate that mild dehydration can modify the cerebrovascular response to the CPT, with dehydration increasing perceived pain, lowering P ET ,CO2 and, ultimately, blunting the MCAv(mean) response. PMID- 26374271 TI - Compound heterozygous variants in the LARP7 gene as a cause of Alazami syndrome in a Caucasian female with significant failure to thrive, short stature, and developmental disability. AB - Alazami syndrome is an autosomal recessive disease characterized by primordial dwarfism, distinct dysmorphic features, and severe intellectual disability. Since it was first identified in a large consanguineous Arabic family in 2012, additional cases have not been published in the literature. We present a 2-year old Northern European/Caucasian female with short stature, failure to thrive, and developmental delay. Whole exome sequencing (WES) identified two novel pathogenic variants in LARP7 (c.213_214dup and c.651_655del), indicating a diagnosis of Alazami syndrome. The case report describes a novel genotypic and phenotypic presentation of Alazami syndrome, contributing to the current knowledge of the condition as well as the expansion of differential diagnoses for growth restriction and intellectual disability. PMID- 26374272 TI - Novel lithium-nitrogen compounds at ambient and high pressures. AB - Using ab initio evolutionary simulations, we predict the existence of five novel stable Li-N compounds at pressures from 0 to 100 GPa (Li13N, Li5N, Li3N2, LiN2, and LiN5). Structures of these compounds contain isolated N atoms, N2 dimers, polyacetylene-like N chains and N5 rings, respectively. The structure of Li13N consists of Li atoms and Li12N icosahedra (with N atom in the center of the Li12 icosahedron) - such icosahedra are not described by Wade-Jemmis electron counting rules and are unique. Electronic structure of Li-N compounds is found to dramatically depend on composition and pressure, making this system ideal for studying metal-insulator transitions. For example, the sequence of lowest enthalpy structures of LiN3 shows peculiar electronic structure changes with increasing pressure: metal-insulator-metal-insulator. This work also resolves the previous controversies of theory and experiment on Li2N2. PMID- 26374273 TI - Prosthetic breast reconstruction in previously irradiated breasts: A meta analysis. AB - BACKGROUND AND OBJECTIVES: The present review evaluated the impacts of pre reconstruction radiotherapy on outcome of prosthetic breast reconstruction and compared the safety of prosthetic reconstruction with that of other modalities, including autologous tissue reconstruction and the combination of flap and implant in the setting of pre-reconstruction radiation. METHODS: Studies presenting outcomes of prosthetic breast reconstruction in the setting of pre reconstruction radiation published in the past 10 years were identified and reviewed. RESULTS: Twenty studies were analyzed. Prosthetic reconstruction in previously irradiated breasts showed significantly increased risks for complications, including reconstruction failure (relative risk, 2.58; 95% confidence interval, 1.86-3.57) than those cases without radiation, regardless of the specific surgical technique used, including one-/two-stage reconstruction, use of an acellular dermal matrix or not, and the timing of the reconstruction (immediate/delayed). Autologous tissue reconstruction and a combination flap and implant showed a 92% and 72% decreased risk of reconstruction failure, respectively, in previously irradiated breasts compared with that of prosthetic reconstruction. CONCLUSIONS: The results suggest that prior irradiation significantly increases the risk of complications in patients undergoing prosthetic reconstruction, and using an autologous flap or combining it with an implant can be considered to reconstruct previously irradiated breasts. PMID- 26374275 TI - Sexual selection has minimal impact on effective population sizes in species with high rates of random offspring mortality: An empirical demonstration using fitness distributions. AB - The effective population size (N(e)) is a fundamental parameter in population genetics that influences the rate of loss of genetic diversity. Sexual selection has the potential to reduce N(e) by causing the sex-specific distributions of individuals that successfully reproduce to diverge. To empirically estimate the effect of sexual selection on N(e), we obtained fitness distributions for males and females from an outbred, laboratory-adapted population of Drosophila melanogaster. We observed strong sexual selection in this population (the variance in male reproductive success was ~14 times higher than that for females), but found that sexual selection had only a modest effect on N(e), which was 75% of the census size. This occurs because the substantial random offspring mortality in this population diminishes the effects of sexual selection on N(e), a result that necessarily applies to other high fecundity species. The inclusion of this random offspring mortality creates a scaling effect that reduces the variance/mean ratios for male and female reproductive success and causes them to converge. Our results demonstrate that measuring reproductive success without considering offspring mortality can underestimate Ne and overestimate the genetic consequences of sexual selection. Similarly, comparing genetic diversity among different genomic components may fail to detect strong sexual selection. PMID- 26374276 TI - Multiple helical configuration and quantity threshold of graphene nanoribbons inside a single-walled carbon nanotube. AB - Molecular dynamics simulation has been carried out to explore the configuration and quantity threshold of multiple graphene nanoribbons (GNRs) in single-walled carbon nanotube (SWCNT). The simulation results showed that several GNRs tangled together to form a perfect spiral structure to maximize the pi-pi stacking area when filling inside SWCNT. The formation of multiple helical configuration is influenced by the combined effect of structure stability, initial arrangement and tube space, meanwhile its forming time is related to helical angle. The simulated threshold of GNRs in SWCNT decreases with GNR width but increases with SWCNT diameter, and two formulas have come up in this study to estimate the quantity threshold for GNRs. It has been found that multilayered graphite is hard to be stripped in SWCNT because the special helical configuration with incompletely separated GNRs is metastable. This work provides a possibility to control the configuration of GNR@SWCNT. PMID- 26374277 TI - Pathologic Findings and Trends in Mortality in the Beluga (Delphinapterus leucas) Population of the St Lawrence Estuary, Quebec, Canada, From 1983 to 2012. AB - An isolated population of beluga (Delphinapterus leucas) inhabits the St Lawrence Estuary, Quebec, Canada. This population has failed to recover despite the prohibition of hunting >30 years ago, suggesting the presence of other limiting factors. The authors summarize the reported causes of death and propose risk factors to explain the lack of recovery of this population. From 1983 to 2012, a total of 472 beluga were found stranded. Complete necropsies were carried out on 222 beluga, including 178 adults, 25 juveniles, and 19 newborn calves. Infectious diseases, the most prevalent cause of mortality in this population, accounted for the death of one-third of all beluga (32%). Verminous pneumonia was the cause of mortality of 13 juvenile beluga (52% of juvenile beluga). A total of 39 malignant neoplasms, diagnosed in 35 beluga, caused the death of 31 beluga (20% of beluga >19 years old). Median age at diagnosis of cancer was 48 years (range, 30-61 years). Dystocia and postpartum complications were the cause of death in 18 beluga, accounting for 19% of the females >19 years old examined. The occurrence of parturition-associated complications, as well as mortality of calves <1 year old, have increased recently in this population and may be the probable cause of the recent decrease in the size of this population. One of the hypotheses proposed to explain the unusually high occurrence of some of the pathologic conditions observed in this population is chronic exposure to environmental contaminants. PMID- 26374278 TI - Unusual Necrotizing Encephalitis in Raccoons and Skunks Concurrently Infected With Canine Distemper Virus and Sarcocystis sp. AB - Canine distemper virus commonly infects free-ranging, terrestrial mesopredators throughout the United States. Due to the immunosuppressive effects of the virus, concurrent opportunistic infections are also common. Among these, secondary systemic protozoal infections have been described in a number of species. We report an unusual presentation of necrotizing encephalitis associated withSarcocystissp in four raccoons and one skunk concurrently infected with canine distemper virus. Lesions were characterized by variably sized necrotizing cavitations composed of abundant mineral admixed with inflammatory cells and protozoa.Sarcocystissp was confirmed via immunohistochemistry using a monoclonal antibody toSarcocystis neurona The pathologic changes are similar to lesions in human AIDS patients infected withToxoplasma gondii. PMID- 26374279 TI - On a Family of Achievement and Shortfall Inequality Indices. AB - This paper identifies a family of absolute consistent inequality indices using a weakly decomposable postulate suggested by Ebert. Because one member employs an Atkinson type aggregation we refer to it as the Atkinson index of consistent inequality. A second member of this family parallels the Kolm index of inequality. Two innovative features of these indices are that no specific structure is imposed on the form of the index at the outset and no transformation of any existing index is considered to ensure consistency. Each of them regards an achievement distribution as equally unequal as the corresponding shortfall distribution. We apply these indices to study inequality in grip strength among 50+ year-old Europeans. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26374280 TI - COPD and its comorbidities: Impact, measurement and mechanisms. AB - Chronic obstructive pulmonary disease (COPD) frequently coexists with other conditions often known as comorbidities. The prevalence of most of the common comorbid conditions that accompany COPD has been widely reported. It is also recognized that comorbidities have significant health and economic consequences. Nevertheless, there is scant research examining how comorbidities should be assessed and managed in the context of COPD. Also, the underlying mechanisms linking COPD with its comorbidities are still not fully understood. Owing to these knowledge gaps, current disease-specific approaches provide clinicians with little guidance in terms of managing comorbid conditions in the clinical care of multi-diseased COPD patients. This review discusses the concepts of comorbidity and multi-morbidity in COPD in relation to the overall clinical outcome of COPD management. It also summarizes some of the currently available clinical scores used to measure comorbid conditions and their prognostic abilities. Furthermore, recent developments in the proposed mechanisms linking COPD with its comorbidities are discussed. PMID- 26374281 TI - Point-of-care haemoglobin measurement - state of the art or a bleeding nuisance? PMID- 26374282 TI - Chiral Cationic Cp(x)Ru(II) Complexes for Enantioselective Yne-Enone Cyclizations. AB - The cyclopentadienyl (Cp) group is a ligand of great importance for many transition-metal complexes used in catalysis. Cationic CpRu(II) complexes with three free coordination sites are highly versatile catalysts for many atom economic transformations. We report the synthesis of a family of Cp(x)Ru(II) complexes with chiral Cp ligands keeping the maximum number of available coordination sites. The cationic members are efficient and selective catalysts for yne-enone cyclizations via formal hetero-Diels-Alder reactions. The transformation proceeds in <1 h at -20 degrees C and provides pyrans in up to 99:1 er. Unsaturated ester or Weinreb-amide substrates directly yield the iridoid skeleton. PMID- 26374283 TI - Lymphoplasmacytic lymphoma: What we need to know. PMID- 26374284 TI - CD44 as a drug delivery target in human cancers: where are we now? AB - In the treatment of cancers, the dual goals of drug targeting are to deliver therapeutic agents more selectively to tumor tissue and to minimize exposure of normal tissues and organs to those agents, the latter causing toxicities that limit treatment and thereby attenuate clinical efficacy. CD44, a transmembrane proteoglycan, has been considered as a targetable candidate to generate a cancer specific drug delivery axis. Although numerous preclinical studies showed promising results exploiting CD44 as such a target, results of two clinical trials, including a Phase III registration trial, have been very disappointing. Herein, we discuss the potential underlying causes that might have led to such failures, as well as the future of CD44-targeted cancer treatment. PMID- 26374285 TI - Oncology 2020: a drug development and approval paradigm. PMID- 26374286 TI - Era-by-era improvement in survival for elderly patients with Hodgkin lymphoma; outcome data from a large population-based cohort. PMID- 26374287 TI - Is chemotherapy still an option in the treatment of melanoma? PMID- 26374288 TI - Host genetic variation impacts microbiome composition across human body sites. AB - BACKGROUND: The composition of bacteria in and on the human body varies widely across human individuals, and has been associated with multiple health conditions. While microbial communities are influenced by environmental factors, some degree of genetic influence of the host on the microbiome is also expected. This study is part of an expanding effort to comprehensively profile the interactions between human genetic variation and the composition of this microbial ecosystem on a genome- and microbiome-wide scale. RESULTS: Here, we jointly analyze the composition of the human microbiome and host genetic variation. By mining the shotgun metagenomic data from the Human Microbiome Project for host DNA reads, we gathered information on host genetic variation for 93 individuals for whom bacterial abundance data are also available. Using this dataset, we identify significant associations between host genetic variation and microbiome composition in 10 of the 15 body sites tested. These associations are driven by host genetic variation in immunity-related pathways, and are especially enriched in host genes that have been previously associated with microbiome related complex diseases, such as inflammatory bowel disease and obesity-related disorders. Lastly, we show that host genomic regions associated with the microbiome have high levels of genetic differentiation among human populations, possibly indicating host genomic adaptation to environment-specific microbiomes. CONCLUSIONS: Our results highlight the role of host genetic variation in shaping the composition of the human microbiome, and provide a starting point toward understanding the complex interaction between human genetics and the microbiome in the context of human evolution and disease. PMID- 26374289 TI - Vasopressor use as a surrogate for post-intubation hemodynamic instability is associated with in-hospital and 90-day mortality: a retrospective cohort study. AB - BACKGROUND: Evidence is lacking for what defines post-intubation hypotension in the intensive care unit (ICU). If a valid definition could be used, the potential exists to evaluate possible risk factors and thereby improve post-intubation. Thus, our objectives were to arrive at the best surrogate for post-intubation hypotension that accurately predicts both in-hospital and 90-day mortality in a population of ICU patients and to report mortality rates between the exposed and unexposed cohorts. METHODS: We conducted a retrospective cohort study of emergent endotracheal intubations in a medical-surgical ICU from January 1, 2010 to December 31, 2011 to evaluate surrogates for post-intubation hypotension that would predict in-hospital and 90-day mortality followed by an analysis of exposed versus unexposed using our best surrogate. Patients were >=18 years of age, underwent emergent intubation during their first ICU admission, and did not meet any of the surrogates 60 min pre-intubation. RESULTS: The six surrogates evaluated 60 min post-intubation were those with any systolic blood pressures <=90 mmHg, any mean arterial pressures <=65 mmHg, reduction in median systolic blood pressures of >=20%, any vasopressor administration, any non-sinus rhythm and, fluid administration of >=30 ml/kg. A total of 147 patients were included. Of the six surrogates, only the administration of any vasopressor 60 min post intubation remained significant for mortality. Twenty-nine patients were then labeled as hemodynamically unstable and compared to the 118 patients labeled as hemodynamically stable. After adjusting for confounders, the hemodynamically unstable group had a significantly higher in-hospital and 90-day mortality [OR (95% CI); 3.84 (1.31-11.57) (p value = 0.01) and 2.37 (1.18-4.61) (p-value = 0.02)]. CONCLUSIONS: Emergently intubated patients manifesting hemodynamic instability after but not before intubation, as measured by vasoactive administration 60 min post-intubation, have a higher association with in-hospital and 90-day mortality. PMID- 26374291 TI - Thermorudis pharmacophila sp. nov., a novel member of the class Thermomicrobia isolated from geothermal soil, and emended descriptions of Thermomicrobium roseum, Thermomicrobium carboxidum, Thermorudis peleae and Sphaerobacter thermophilus. AB - An aerobic, thermophilic and cellulolytic bacterium, designated strain WKT50.2T, was isolated from geothermal soil at Waikite, New Zealand. Strain WKT50.2T grew at 53-76 degrees C and at pH 5.9-8.2. The DNA G+C content was 58.4 mol%. The major fatty acids were 12-methyl C18 : 0 and C18 : 0. Polar lipids were all linked to long-chain 1,2-diols, and comprised 2-acylalkyldiol-1-O-phosphoinositol (diolPI), 2-acylalkyldiol-1-O-phosphoacylmannoside (diolP-acylMan), 2 acylalkyldiol-1-O-phosphoinositol acylmannoside (diolPI-acylMan) and 2 acylalkyldiol-1-O-phosphoinositol mannoside (diolPI-Man). Strain WKT50.2T utilized a range of cellulosic substrates, alcohols and organic acids for growth, but was unable to utilize monosaccharides. Robust growth of WKT50.2T was observed on protein derivatives. WKT50.2T was sensitive to ampicillin, chloramphenicol, kanamycin, neomycin, polymyxin B, streptomycin and vancomycin. Metronidazole, lasalocid A and trimethoprim stimulated growth. Phylogenetic analysis of 16S rRNA gene sequences showed that WKT50.2T belonged to the class Thermomicrobia within the phylum Chloroflexi, and was most closely related to Thermorudis peleae KI4T (99.6% similarity). DNA-DNA hybridization between WKT50.2T and Thermorudis peleae DSM 27169T was 18.0%. Physiological and biochemical tests confirmed the phenotypic and genotypic differentiation of strain WKT50.2T from Thermorudis peleae KI4T and other members of the Thermomicrobia. On the basis of its phylogenetic position and phenotypic characteristics, we propose that strain WKT50.2T represents a novel species, for which the name Thermorudis pharmacophila sp. nov. is proposed, with the type strain WKT50.2T ( = DSM 26011T = ICMP 20042T). Emended descriptions of Thermomicrobium roseum, Thermomicrobium carboxidum, Thermorudis peleae and Sphaerobacter thermophilus are also proposed, and include the description of a novel respiratory quinone, MK-8 2,3-epoxide (23%), in Thermomicrobium roseum. PMID- 26374290 TI - Experimental validation of in silico model-predicted isocitrate dehydrogenase and phosphomannose isomerase from Dehalococcoides mccartyi. AB - Gene sequences annotated as proteins of unknown or non-specific function and hypothetical proteins account for a large fraction of most genomes. In the strictly anaerobic and organohalide respiring Dehalococcoides mccartyi, this lack of annotation plagues almost half the genome. Using a combination of bioinformatics analyses and genome-wide metabolic modelling, new or more specific annotations were proposed for about 80 of these poorly annotated genes in previous investigations of D. mccartyi metabolism. Herein, we report the experimental validation of the proposed reannotations for two such genes (KB1_0495 and KB1_0553) from D. mccartyi strains in the KB-1 community. KB1_0495 or DmIDH was originally annotated as an NAD(+)-dependent isocitrate dehydrogenase, but biochemical assays revealed its activity primarily with NADP(+) as a cofactor. KB1_0553, also denoted as DmPMI, was originally annotated as a hypothetical protein/sugar isomerase domain protein. We previously proposed that it was a bifunctional phosphoglucose isomerase/phosphomannose isomerase, but only phosphomannose isomerase activity was identified and confirmed experimentally. Further bioinformatics analyses of these two protein sequences suggest their affiliation to potentially novel enzyme families within their respective larger enzyme super families. PMID- 26374292 TI - Effects of kiwi consumption on plasma lipids, fibrinogen and insulin resistance in the context of a normal diet. AB - BACKGROUND AND AIMS: Among fruits, kiwi is one of the richest in vitamins and polyphenols and has strong anti-oxidant effects. We aimed to analyze the relationship between the consumption of kiwi and plasma lipid values, fibrinogen, and insulin resistance in adults within the context of a normal diet and physical activity. METHODS: Cross-sectional study. Participants (N = 1469), who were free of cardiovascular diseases, completed a visit, which included the collection of information concerning the participant's usual diet and kiwi consumption using a previously validated, semi-quantitative, 137-item food-frequency-questionnaire. Fasting laboratory determinations included plasma lipids, fibrinogen and insulin resistance. Regular physical-activity was determined using accelerometry. RESULTS: Consumers of at least 1 kiwi/week presented higher plasma values of HDL cholesterol (mean difference 4.50 [95% CI: 2.63 to 6.36]) and lower triglyceride values (mean difference -20.03 [95% CI: -6.77 to -33.29]), fibrinogen values (mean difference -13.22 [95% CI: -2.18 to -24.26]) and HOMAir values (mean difference -0.30 [95% CI: -0.09 to -0.50]) (p < 0.05, for all comparisons) than those who consumed less than 1 kiwi per week. In an adjusted logistic regression analysis, this group had a lower odds-ratio for presenting plasmatic fibrinogen concentrations above 400 mg/dL (OR = 0.68, 95% CI 0.49 to 0.95), HDL-Cholesterol plasma values below 45 mg/dL (OR = 0.57, 95% CI 0.36 to 0.91) and a HOMAir above 3 (OR = 0.61, 95% CI 0.37 to 1.00). CONCLUSIONS: Consumption of at least one kiwi/week is associated with lower plasma concentrations of fibrinogen and improved plasma lipid profile in the context of a normal diet and regular exercise. PMID- 26374293 TI - A comparison of indices of glucose metabolism in five black populations: data from modeling the epidemiologic transition study (METS). AB - BACKGROUND: Globally, Africans and African Americans experience a disproportionate burden of type 2 diabetes, compared to other race and ethnic groups. The aim of the study was to examine the association of plasma glucose with indices of glucose metabolism in young adults of African origin from 5 different countries. METHODS: We identified participants from the Modeling the Epidemiologic Transition Study, an international study of weight change and cardiovascular disease (CVD) risk in five populations of African origin: USA (US), Jamaica, Ghana, South Africa, and Seychelles. For the current study, we included 667 participants (34.8 +/- 6.3 years), with measures of plasma glucose, insulin, leptin, and adiponectin, as well as moderate and vigorous physical activity (MVPA, minutes/day [min/day]), daily sedentary time (min/day), anthropometrics, and body composition. RESULTS: Among the 282 men, body mass index (BMI) ranged from 22.1 to 29.6 kg/m(2) in men and from 25.8 to 34.8 kg/m(2) in 385 women. MVPA ranged from 26.2 to 47.1 min/day in men, and from 14.3 to 27.3 min/day in women and correlated with adiposity (BMI, waist size, and % body fat) only among US males after controlling for age. Plasma glucose ranged from 4.6 +/- 0.8 mmol/L in the South African men to 5.8 mmol/L US men, while the overall prevalence for diabetes was very low, except in the US men and women (6.7 and 12 %, respectively). Using multivariate linear regression, glucose was associated with BMI, age, sex, smoking hypertension, daily sedentary time but not daily MVPA. CONCLUSION: Obesity, metabolic risk, and other potential determinants vary significantly between populations at differing stages of the epidemiologic transition, requiring tailored public health policies to address local population characteristics. PMID- 26374294 TI - Correlation of PET-CT nodal SUVmax with p16 positivity in oropharyngeal squamous cell carcinoma. AB - BACKGROUND: The incidence of human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) has been rising in recent years. Given the clinical impact of HPV/p16 positivity in OPSCC, identifying surrogate markers of this disease early in the diagnostic work-up of these patients could improve patient care. METHODS: Demographic, pathologic, staging and PET-CT data from patients diagnosed with OPSCC from 2009-2014 were obtained from a prospectively collected provincial cancer registry. Tumor HPV/p16 status was correlated to the maximum standard uptake value (SUVmax) of the primary tumor and cervical nodes. Comparisons of means and multinomial regression models were used to determine associations between p16 status and SUVmax. A diagnostic odds ratio was calculated using a cut off value for predicting HPV/p16 positivity based on nodal SUVmax. RESULTS: PET-CT and HPV/p16 data was obtained for 65 patients treated surgically for OPSCC. Significantly higher nodal SUVmax was associated with HPV/p16 positive nodes (SUVmax 10.8 vs 7.9). No significant differences were seen between HPV/p16 positive vs negative primary tumor SUVmax (10.3 vs 13.7). In combination with other clinical parameters, higher nodal SUVmax was highly correlated with HPV/p16 positivity. CONCLUSION: Elevated nodal SUVmax is a significant predictor of HPV/p16 positive disease. PMID- 26374295 TI - Left Ventricular Structure and Risk of Cardiovascular Events: A Framingham Heart Study Cardiac Magnetic Resonance Study. AB - BACKGROUND: Elevated left ventricular mass index (LVMI) and concentric left ventricular (LV) remodeling are related to adverse cardiovascular disease (CVD) events. The predictive utility of LV concentric remodeling and LV mass in the prediction of CVD events is not well characterized. METHODS AND RESULTS: Framingham Heart Study Offspring Cohort members without prevalent CVD (n=1715, 50% men, aged 65+/-9 years) underwent cardiovascular magnetic resonance for LVMI and geometry (2002-2006) and were prospectively followed for incident CVD (myocardial infarction, coronary insufficiency, heart failure, stroke) or CVD death. Over 13 808 person-years of follow-up (median 8.4, range 0.0 to 10.5 years), 85 CVD events occurred. In multivariable-adjusted proportional hazards regression models, each 10-g/m(2) increment in LVMI and each 0.1 unit in relative wall thickness was associated with 33% and 59% increased risk for CVD, respectively (P=0.004 and P=0.009, respectively). The association between LV mass/LV end-diastolic volume and incident CVD was borderline significant (P=0.053). Multivariable-adjusted risk reclassification models showed a modest improvement in CVD risk prediction with the incorporation of cardiovascular magnetic resonance LVMI and measures of LV concentricity (C-statistic 0.71 [95% CI 0.65 to 0.78] for the model with traditional risk factors only, improved to 0.74 [95% CI 0.68 to 0.80] for the risk factor model additionally including LVMI and relative wall thickness). CONCLUSIONS: Among adults free of prevalent CVD in the community, greater LVMI and LV concentric hypertrophy are associated with a marked increase in adverse incident CVD events. The potential benefit of aggressive primary prevention to modify LV mass and geometry in these adults requires further investigation. PMID- 26374296 TI - Think Small and Examine the Constituents of Left Ventricular Hypertrophy and Heart Failure: Cardiomyocytes Versus Fibroblasts, Collagen, and Capillaries in the Interstitium. PMID- 26374298 TI - Cognitive function in idiopathic pulmonary fibrosis. AB - The purpose of this study was to investigate whether there is evidence that individuals with severe idiopathic pulmonary fibrosis (IPF) have cognitive deficits when compared to individuals with healthy lungs. Participants completed five neuropsychological tests: Trail Making Test (TMT) A and B, Stroop Color Word Test (1, 2, 3), Hopkins Verbal Learning Test, Boston Naming Test, and Grooved Pegboard Test, additionally, the short form-36 and Beck Depression Index. Twelve participants (7 male, mean age 69.3, 9.4 years) comprised the severe IPF group defined by a diffusion capacity for carbon monoxide (DLCO) <30%. Thirty-four patients (22 male, mean age 63.2, 9.6 years) comprised the mild-to-moderate group with a DLCO >30%. Participating spouses (n = 15, 4 male) served as the control group and had a mean age of 66.0, 10.8 years. Controlling for gender and age, the severe group had a significantly longer mean TMT B time (69.4, 135.9 seconds) than the mild group and the control group (86.7 seconds vs 83.2 seconds; p = 0.004 and 0.008 respectively), suggesting inferior performance on tasks requiring speed divided attention. In addition, the severe group had a significantly lower number of correctly identified colors in the Stroop 3 test (22.4 vs 30.6 vs 38.6; p < 0.001), suggesting slower processing speeds when requiring suppression of a familiar response. Participants with severe IPF had worse cognitive function than mild IPF or control subjects. Further research is needed to explain these findings and to develop interventions tailored to address these deficits. PMID- 26374297 TI - Effect of Extended-Release Niacin on High-Density Lipoprotein (HDL) Functionality, Lipoprotein Metabolism, and Mediators of Vascular Inflammation in Statin-Treated Patients. AB - BACKGROUND: The aim of this study was to explore the influence of extended release niacin/laropiprant (ERN/LRP) versus placebo on high-density lipoprotein (HDL) antioxidant function, cholesterol efflux, apolipoprotein B100 (apoB) containing lipoproteins, and mediators of vascular inflammation associated with 15% increase in high-density lipoprotein cholesterol (HDL-C). Study patients had persistent dyslipidemia despite receiving high-dose statin treatment. METHODS AND RESULTS: In a randomized double-blind, placebo-controlled, crossover trial, we compared the effect of ERN/LRP with placebo in 27 statin-treated dyslipidemic patients who had not achieved National Cholesterol Education Program-ATP III targets for low-density lipoprotein cholesterol (LDL-C). We measured fasting lipid profile, apolipoproteins, cholesteryl ester transfer protein (CETP) activity, paraoxonase 1 (PON1) activity, small dense LDL apoB (sdLDL-apoB), oxidized LDL (oxLDL), glycated apoB (glyc-apoB), lipoprotein phospholipase A2 (Lp PLA2), lysophosphatidyl choline (lyso-PC), macrophage chemoattractant protein (MCP1), serum amyloid A (SAA) and myeloperoxidase (MPO). We also examined the capacity of HDL to protect LDL from in vitro oxidation and the percentage cholesterol efflux mediated by apoB depleted serum. ERN/LRP was associated with an 18% increase in HDL-C levels compared to placebo (1.55 versus 1.31 mmol/L, P<0.0001). There were significant reductions in total cholesterol, triglycerides, LDL cholesterol, total serum apoB, lipoprotein (a), CETP activity, oxLDL, Lp PLA2, lyso-PC, MCP1, and SAA, but no significant changes in glyc-apoB or sdLDL apoB concentration. There was a modest increase in cholesterol efflux function of HDL (19.5%, P=0.045), but no change in the antioxidant capacity of HDL in vitro or PON1 activity. CONCLUSIONS: ERN/LRP reduces LDL-associated mediators of vascular inflammation, but has varied effects on HDL functionality and LDL quality, which may counter its HDL-C-raising effect. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01054508. PMID- 26374299 TI - Physical activity levels improve following discharge in people admitted to hospital with an acute exacerbation of chronic obstructive pulmonary disease. AB - This study aimed to determine the physical activity level of people admitted to hospital with an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and whether physical activity changed immediately after discharge and 6 weeks post hospital admission. In this prospective observational study, people admitted to hospital with an AECOPD had physical activity levels monitored using the SenseWear((r)) Armband (model MF-SW) for 3 days in hospital (T1), during the first week at home following discharge (T2), and at home during the sixth week after admission (T3). Fifty participants (mean age (SD) 71 (10) years) completed the study. There was a linear increase in average steps per day over the three time periods (T1, mean (SD) 1385 (1972) steps/day; T2, 2040 (2680); T3, 2328 (2745); analysis of variance (ANOVA) p = 0.001) and time spent in moderate activity (3.0-6.0 metabolic equivalents; minutes/day) (T1, mean (SD) 16 (27) minutes/day; T2, 32 (46) minutes/day; T3, 35 (58) minutes/day; ANOVA p = 0.008). For both outcomes, post hoc t-tests showed significant improvements from T1 to T2 and from T1 to T3, but not between T2 and T3. Physical activity was low in hospital and significantly improved in the week after discharge but showed no further significant improvement at 6 weeks following a hospitalized AECOPD. PMID- 26374300 TI - Prognostic value of forced expiratory volume in 1 second/forced vital capacity in idiopathic pulmonary fibrosis. AB - Emphysema on high-resolution computed tomography of the chest is the recent focus in the general practice in idiopathic pulmonary fibrosis (IPF). However, adequate attention has not been paid to obstructive disorder. Therefore, we retrospectively evaluated the association between the degree of airway obstruction and longevity in IPF subjects, with a hypothesis that lower forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) has an impact on prognosis. One hundred and fourteen consecutive IPF subjects who had been diagnosed with IPF and had undergone evaluation including pulmonary function test from January 2008 to May 2013 were included in the study. The relationship between baseline data and survival was examined. FEV1/FVC was widely distributed, ranging from 48.6% to 100%. On both univariate and multivariate Cox's regression analyses, lower FEV1/FVC was significantly associated with better survival (hazard ratio of 1.07 and 1.04 and 95% confidential interval of 1.03-1.10 and 1.01-1.08, respectively). Even on analysis with backward selection, FEV1/FVC remained a significant prognostic factor. FEV1/FVC is widely distributed and negatively predicts survival in IPF. A FEV1/FVC should be assessed in "real world" general practice. Also, the effect of smoking on the clinical course of IPF should be investigated further. PMID- 26374301 TI - Simple cardiovagal and adrenergic function tests in carotid artery stenosis patients as a potential tool for determining a transient autonomic dysfunction. AB - PURPOSE: The arterial baroreflex depends on the integrity of the afferent limb, which can be quantified using the baroreceptor's sensitivity (BRS) during the Valsalva maneuver (VM). The aim of this study was to evaluate, using autonomic nervous system tests, the autonomic function in patients after a carotid artery angioplasty (CAS). METHODS: We evaluated the changes in blood pressure (BP) during the VM (Valsalva ratio, BRS, sympathetic indexes) in 41 patients with symptomatic, unilateral, internal carotid artery stenosis. RESULTS: The Valsalva ratio between the baseline and the post-procedural day (1.3 +/- 0.1 vs 1.44 +/- 0.3; P = 0.002) and the post-procedural day and a month later (1.44 +/- 0.3 vs 1.3 +/- 0.3; P = 0.0002) revealed significant differences. This was confirmed with a cardiovagal BRS test. However, the adrenergic BRS did not reveal any differences. Sympathetic indexes [BP fall (SI1) and recovery during phase 2 (SI2)] showed differences for the periods before and a day after the treatment (36.9 +/- 18.0 vs 27.2 +/- 21.4 and 7.1 +/- 13.1 vs 3.0 +/- 8.2, respectively; P = 0.004) and for SI1 a day and a month after the treatment (27.2 +/- 21.4 vs 37.1 +/- 21.8; P = 0.036). The dynamic ranges between S1 and S3 (the difference in the BP between the baseline and the end of phase 2) were also different (P = 0.007 and P = 0.044, respectively). CONCLUSION: We found heterogeneous responses in the BP regulation obtained with the Valsalva maneuver in our patients; however, we could not confirm that CAS provoked any long-term autonomic dysfunction, except for 1 day after the procedure. PMID- 26374302 TI - Erectile dysfunction (ED) after ischemic stroke: association between prevalence and site of lesion. AB - PURPOSE: Stroke may cause or worsen erectile dysfunction (ED). Post-stroke ED prevalence and association with stroke location are not well established. Therefore, we assessed post-stroke ED prevalence in relation to ischemic lesion locations and stroke severity. METHODS: In 57 men (62.6 +/- 10.5 years) who had ischemic stroke within 24 months prior to evaluation, we used the five-item International Index of Erectile Function questionnaire (IIEF5) to evaluate ED prevalence after stroke and retrospectively 3 months prior to stroke. IIEF5 scores range from 5 to 25; scores below 22 indicate ED. We estimated stroke severity upon hospital admission, using the National Institute of Health Stroke Scale (NIHSS), and determined stroke location from cranial computed tomography or magnetic resonance imaging. We compared pre- and post-stroke results with those of 22 control persons (61.7 +/- 11.2 years), calculated correlations between IIEF5 scores and NIHSS scores, and compared ED prevalence with stroke locations (significance: p < 0.05). RESULTS: ED was reported by 45/57 patients after stroke, 26/57 patients before stroke, and 6/22 control persons. Patients' IIEF5 values were significantly lower [median 16 interquartile range (IQR) 3.5-20.5] after than before stroke (median 23, IQR 19.0-24.0) and lower than in controls (median 24, IQR 19.8-25.0). Pre- and post-stroke IIEF5 scores did not correlate with the patients' NIHSS scores at stroke onset (p > 0.05). ED was associated with middle cerebral artery infarction in 27/34, posterior cerebral artery infarction in 4/5, anterior cerebral artery infarction in 1/1, basal ganglia infarction in 3/3, brain stem infarction in 8/10, cerebellar infarction in 2/5, and lesions in more than one region in 1/1 patients. CONCLUSIONS: Disruption of the central network assuring erection might contribute to increased ED severity and prevalence after stroke. Anti-erectile effects of functional and psychological impairment or medication added after stroke may also contribute to ED but must be evaluated in larger patients groups. PMID- 26374303 TI - Skin sympathetic function in complex regional pain syndrome type 1. AB - PURPOSE: Cutaneous sympathetic pathophysiology in complex regional pain syndrome type 1 (CRPS-1) is not yet completely understood. To evaluate cutaneous sympathetic dysfunction in CRPS-1, we evaluated sympathetic sweat response (SSwR) and skin vasomotor reflex (SkVR) in CRPS-1 patients. METHODS: We studied 10 CRPS 1 patients (age 41 +/- 13 years; 5 females and 5 males; disease duration 20 +/- 22 months) and 10 healthy subjects (age 44 +/- 13 years; 3 females and 7 males). SkVRs and SSwRs to several sympathetic activating procedures were recorded on the palms of the CRPS-1 patients (affected side) and controls (right side). RESULTS: There were no significant differences in the baselines of sweat output and skin blood flow between the CRPS-1 and control groups. SSwR and SkVR amplitudes were significantly lower in the CRPS-1 group than in the control group. There was no significant correlation between disease duration and SSwR or SkVR amplitudes among the patients. CONCLUSIONS: The reduced SSwRs and SkVRs in the affected limb of our CRPS-1 patients may reflect underlying damage to the sympathetic postganglionic fibres. PMID- 26374306 TI - Principles of Whole-Genome Amplification. AB - Modern molecular biology relies on large amounts of high-quality genomic DNA. However, in a number of clinical or biological applications this requirement cannot be met, as starting material is either limited (e.g., preimplantation genetic diagnosis (PGD) or analysis of minimal residual cancer) or of insufficient quality (e.g., formalin-fixed paraffin-embedded tissue samples or forensics). As a consequence, in order to obtain sufficient amounts of material to analyze these demanding samples by state-of-the-art modern molecular assays, genomic DNA has to be amplified. This chapter summarizes available technologies for whole-genome amplification (WGA), bridging the last 25 years from the first developments to currently applied methods. We will especially elaborate on research application, as well as inherent advantages and limitations of various WGA technologies. PMID- 26374304 TI - Changes in heart rate variability after sitting following interscalene block. AB - PURPOSE: Hypotensive bradycardic events (HBEs) occur in 5-28% of patients undergoing arthroscopic shoulder surgery in the sitting position after an interscalene brachial plexus block (ISBPB). The objective of this study was to investigate the effects of the sitting position following ISBPB on heart rate variability (HRV). METHODS: In this prospective case-control study, we evaluated 64 patients undergoing arthroscopic shoulder surgery under ISBPB and 49 nonsurgical control subjects. HRV power spectral analysis parameters were measured (and natural log-transformed) before ISBPB and after changing to the sitting position. The patients experiencing HBEs were assigned to the HBE group, and the remaining patients were assigned to the non-HBE group. RESULTS: HBEs developed in 18 patients (28.1%). Changing from the supine position to the sitting position after ISBPB did not induce a significant increase in the natural log-transformed ratio of low-frequency to high-frequency power (lnLF/HF). A significant decrease in natural log-transformed high-frequency power (lnHF) was observed compared to the control group, who presented a significant increase in lnLF/HF and an insignificant change in lnHF. lnHF was found to be significantly higher in the HBE group compared to the non-HBE group. CONCLUSIONS: Sustained vagal activity with a failed shift in the sympathovagal balance toward sympathetic predominance in response to sitting after ISBPB is associated with the development of HBE. PMID- 26374305 TI - Study protocol for a multicenter investigation of reablement in Norway. AB - BACKGROUND: Reablement is a promising new rehabilitation model, which is being implemented in some Western countries to meet current and future needs for home based services. There is a need for further investigation of the effects of reablement among community-dwelling adults in terms of clinical and economic outcomes. This study will investigate the effectiveness of reablement in home dwelling adults compared with standard treatment in terms of daily activities, physical functioning, health-related quality of life, coping, mental health, use of health care services, and costs. METHODS/DESIGN: The study is a multicenter controlled trial. In total, 44 Norwegian municipalities will participate, including eight municipalities as a control group. For three municipalities with two zones, one will be assigned to the control group and the other to the intervention group. The experimental group will be offered reablement and the control group standard treatment. The sample will comprise approximately 750 participants. People will be eligible if they are home-dwelling adults, understand Norwegian, and have functional decline. Participants will be assessed at baseline, and after 10 weeks, 6 months, and 12 months. The primary outcome will be activity and participation measured by the Canadian Occupational Performance Measure. Physical functioning will be measured by the Short Physical Performance Battery and health-related quality of life by the European Quality of Life Scale. Coping will be measured by the Sense of Coherence questionnaire and mental health by the Mental Health Continuum Short Form. Costs will be generated based on registered working hours in different professions. Data analyses will be performed according to intention to treat. Univariate analysis of covariance will be used to investigate differences between the groups at baseline and the end of intervention. The data will be organized into two levels using a multilevel structure, i.e., individuals and municipalities, which will be analyzed using linear mixed-effects models. The working hours data (panel data) will be analyzed with random mixed-effects regression models. The cost-effectiveness of reablement will be evaluated according to the incremental cost-effectiveness ratio and uncertainty will be explored via the bootstrap method. DISCUSSION: The findings will make an important contribution to knowledge of rehabilitation approaches for community-dwelling adults. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov on October 24, 2014, identifier: NCT02273934 . PMID- 26374307 TI - Bias in Whole Genome Amplification: Causes and Considerations. AB - Whole genome amplification (WGA) is a widely used molecular technique that is becoming increasingly necessary in genetic research on a range of sample types including individual cells, fossilized remains and entire ecosystems. Multiple methods of WGA have been developed, each with specific strengths and weaknesses, but with a common defect in that each method distorts the initial template DNA during the course of amplification. The type, extent, and circumstance of the bias vary with the WGA method and particulars of the template DNA. In this review, we endeavor to discuss the types of bias introduced, the susceptibility of common WGA techniques to these bias types, and the interdependence between bias and characteristics of the template DNA. Finally, we attempt to illustrate some of the criteria specific to the analytical platform and research application that should be considered to enable combination of the appropriate WGA method, template DNA, sequencing platform, and intended use for optimal results. PMID- 26374308 TI - The Single-Cell Lab or How to Perform Single-Cell Molecular Analysis. AB - The increasing interest towards cellular heterogeneity within cell populations has pushed the development of new protocols to isolate and analyze single cells. PCR-based amplification techniques are widely used in this field. However, setting up an experiment and analyzing the results can sometimes be challenging. The aim of this chapter is to provide a general overview on single-cell PCR analysis focusing on the potential pitfalls and on the possible solutions to successfully perform the analysis. PMID- 26374309 TI - Sample Preparation Methods Following CellSearch Approach Compatible of Single Cell Whole-Genome Amplification: An Overview. AB - Single cells are increasingly used to determine the heterogeneity of therapy targets in the genome during the course of a disease. The first challenge using single cells is to isolate these cells from the surrounding cells, especially when the targeted cells are rare. A number of techniques have been developed for this goal, each having specific limitations and possibilities. In this chapter, five of these techniques are discussed in the light of the isolation of circulating tumor cells (CTC) present at extremely low frequency in the blood of patients with metastatic cancer from the perspective of pre-enriched samples by means of CellSearch. The techniques described are micromanipulation, FACS, laser capture microdissection, DEPArray, and microfluidic solutions. All platforms are hampered with a low efficiency and differences in hands-on time and costs are the most important drivers for selection of the optimal platform. PMID- 26374310 TI - Deterministic Whole-Genome Amplification of Single Cells. AB - This chapter describes a single-cell whole genome amplification method (WGA) that has been originally published under the name "Single Cell Comparative Genomic Hybridization (SCOMP)" (Klein et al., Proc Natl Acad Sci U S A 96(8):4494-4499, 1999). The method has recently become available commercially under the name "Ampli1(TM) WGA Kit." It is a PCR-based technique for whole genome amplification (WGA) allowing comprehensive and quite uniform amplification of DNA from low quantities of input DNA material, in particular single cells. The method is based on a ligation-mediated adaptor linker PCR approach. In contrast to other PCR based WGA approaches, both the primer design and mechanism underlying the fragmentation of genome are nonrandom, enabling high priming efficiency and deterministic fragmentation of template DNA. This is particularly important for the design of (diagnostic) assays targeting specific loci. Here, we describe the WGA protocol for amplification of single-cell genomes designed to provide high quality material in quantity sufficient for a number of locus-specific and genome wide downstream assays [e.g., targeted Sanger sequencing, restriction fragment length polymorphism (RFLP), quantitative PCR (qPCR), and array comparative genomic hybridization (CGH)]. PMID- 26374311 TI - Construction of a DNA Library on Microbeads Using Whole Genome Amplification. AB - A polymerase chain reaction (PCR) in water droplets with water-in-oil emulsion (emulsion PCR) facilitates parallel amplification of a single-molecule template. The amplified DNA can be immobilized onto microbeads bound to primer DNA. The product, termed a "bead library", has various applications such as next generation sequencing (NGS) and the directed evolution of various functional biomolecules. Here, we describe a method for genomic library construction on microbeads using emulsion PCR. PMID- 26374312 TI - Heat-Induced Fragmentation and Adapter-Assisted Whole Genome Amplification Using GenomePlex(r) Single-Cell Whole Genome Amplification Kit (WGA4). AB - Whole genome amplification (WGA) is a widely used technique allowing multiplying picogram amounts of target DNA by several orders of magnitude. The technique described here is based on heat-induced random fragmentation yielding DNA strands mainly ranging from 0.1 to 1 kb in length. The fragmented DNA is then subjected to library generation by annealing of adaptor sequences to both ends of the DNA fragments. Using primers hybridizing to the adapter sequences, the DNA is amplified by thermal cycling. This amplification typically yields > 2 mg DNA from a single cell, is suited for amplifying DNA isolated from (partly) degraded samples [e.g. formalin-fixed paraffin-embedded (FFPE) material] and works well when used for array-comparative genome hybridization (array-CGH). PMID- 26374313 TI - Whole Genome Amplification by Isothermal Multiple Strand Displacement Using Phi29 DNA Polymerase. AB - The here described method of isothermal whole genome amplification (iWGA) uses a Phi29 DNA polymerase-based kit (Illustra GenomiPhi V2 DNA Amplification Kit) that amplifies minute quantities of DNA by multiple strand displacement upon random hexamer primer binding. Starting from genomic DNA or single cells this amplification yields up to 5 MUg of iWGA product with fragment lengths of 10 kb and longer. As this amplification lacks the need of fragmenting DNA, its products are well suited for many downstream applications (e.g. sequencing and DNA profiling). On the contrary, degraded DNA samples are not supported by the nature of the amplification and are not well suited. PMID- 26374314 TI - Using Multiplex PCR for Assessing the Quality of Whole Genome Amplified DNA. AB - This chapter describes a simple and inexpensive multiplex PCR-based method to assess the quality of whole genome amplification (WGA) products generated from heat-induced random fragmented DNA. A set of four primer pairs is used to amplify DNA sequences of WGA products in and downstream of GAPDH gene in yielding 100, 200, 300, and 400 bp fragments. PCR products are analyzed by agarose gel electrophoresis and the respective WGA quality is classified according to the number of obtained PCR bands. WGA products that yield three or four PCR bands are considered to be of high quality and yield good results when analyzed by means of array comparative genome hybridization (CGH). PMID- 26374315 TI - Quality Control of Isothermal Amplified DNA Based on Short Tandem Repeat Analysis. AB - This protocol describes the use of a 16plex PCR for the purpose assessing DNA quality after isothermal whole genome amplification (WGA). In short, DNA products, generated by amplification multiple displacement amplification, are forwarded to PCR targeting 15 short tandem repeats (STR) as well as amelogenin generating up to 32 different PCR products. After amplification, the PCR products are separated via capillary electrophoresis and analyzed based on the obtained DNA profiles. Isothermal WGA products of good DNA quality will result in DNA profiles with efficiencies of >90 % of the full DNA profile. PMID- 26374316 TI - Laser Microdissection of FFPE Tissue Areas and Subsequent Whole Genome Amplification by Ampli1TM. AB - Laser microdissection (LMD) and whole genome amplification (WGA) are valuable tools to isolate, purify, and genetically analyze cancer cells from tissue sections. In this chapter, we describe a workflow for microdissecting small regions of interest from cancer tissue, i.e. formalin-fixed paraffin-embedded (FFPE) and cryo-conserved specimens, and subsequent whole genome amplification by a deterministic WGA approach (Ampli1TM WGA). PMID- 26374317 TI - Whole Genome Amplification from Blood Spot Samples. AB - Whole genome amplification is an invaluable technique when working with DNA extracted from blood spots, as the DNA obtained from this source often is too limited for extensive genetic analysis. Two techniques that amplify the entire genome are common. Here, both are described with focus on the benefits and drawbacks of each system. However, in order to obtain the best possible WGA result the quality of input DNA extracted from the blood spot is essential, but also time consumption, flexibility in format and elution volume and price of the technology are factors influencing system choice. Here, three DNA extraction techniques are described and the above aspects are compared between the systems. PMID- 26374318 TI - Analysis of Whole Mitogenomes from Ancient Samples. AB - Ancient mitochondrial DNA has been used in a wide variety of paleontological and archeological studies, ranging from population dynamics of extinct species to patterns of domestication. Most of these studies have traditionally been based on the analysis of short fragments from the mitochondrial control region, analyzed using PCR coupled with Sanger sequencing. With the introduction of high throughput sequencing, as well as new enrichment technologies, the recovery of full mitochondrial genomes (mitogenomes) from ancient specimens has become significantly less complicated. Here we present a protocol to build ancient extracts into Illumina high-throughput sequencing libraries, and subsequent Agilent array-based capture to enrich for the desired mitogenome. Both are based on previously published protocols, with the introduction of several improvements aimed to increase the recovery of short DNA fragments, while keeping the cost and effort requirements low. This protocol was designed for enrichment of mitochondrial DNA in ancient or other degraded samples. However, the protocols can be easily adapted for using for building libraries for shotgun-sequencing of whole genomes, or enrichment of other genomic regions. PMID- 26374319 TI - Copy Number Variation Analysis by Array Analysis of Single Cells Following Whole Genome Amplification. AB - Whole genome amplification is required to ensure the availability of sufficient material for copy number variation analysis of a genome deriving from an individual cell. Here, we describe the protocols we use for copy number variation analysis of non-fixed single cells by array-based approaches following single cell isolation and whole genome amplification. We are focusing on two alternative protocols, an isothermal and a PCR-based whole genome amplification method, followed by either comparative genome hybridization (aCGH) or SNP array analysis, respectively. PMID- 26374320 TI - Whole Genome Amplification in Genomic Analysis of Single Circulating Tumor Cells. AB - Investigation of the genome of organisms is one of the major basics in molecular biology to understand the complex organization of cells. While genomic DNA can easily be isolated from tissues or cell cultures of plant, animal or human origin, DNA extraction from single cells is still challenging. Here, we describe three techniques for the amplification of genomic DNA of fixed single circulating tumor cells (CTC) isolated from blood of cancer patients. This amplification is aimed to increase DNA amounts from those of one cell to yields sufficient for different DNA analyses such as mutational analysis including next-generation sequencing, array-comparative genome hybridization (CGH), and quantitative measurement of gene amplifications. Molecular analysis of CTC as liquid biopsy can be used to identify therapeutic targets in personalized medicine directed, e.g. against human epidermal growth factor receptor 2 (HER2) or epidermal growth factor receptor (EGFR) and to stratify the patients to those therapies. PMID- 26374321 TI - Whole Genome Amplification of Labeled Viable Single Cells Suited for Array Comparative Genomic Hybridization. AB - Understanding details of a complex biological system makes it necessary to dismantle it down to its components. Immunostaining techniques allow identification of several distinct cell types thereby giving an inside view of intercellular heterogeneity. Often staining reveals that the most remarkable cells are the rarest. To further characterize the target cells on a molecular level, single cell techniques are necessary. Here, we describe the immunostaining, micromanipulation, and whole genome amplification of single cells for the purpose of genomic characterization. First, we exemplify the preparation of cell suspensions from cultured cells as well as the isolation of peripheral mononucleated cells from blood. The target cell population is then subjected to immunostaining. After cytocentrifugation target cells are isolated by micromanipulation and forwarded to whole genome amplification. For whole genome amplification, we use GenomePlex((r)) technology allowing downstream genomic analysis such as array-comparative genomic hybridization. PMID- 26374322 TI - Low-Volume On-Chip Single-Cell Whole Genome Amplification for Multiple Subsequent Analyses. AB - Multiple analyses such as DNA profiling, sequencing, or comparative genome hybridization (CGH) done on the single-cell level long for pre-amplification due to the diploid human genome. Isothermal whole genome amplification allows amplification of long DNA templates from single cells. When analysis needs to be performed under rare cell conditions additional care needs to be taken due to the fact that, even after pre-enrichment, few candidate target cells are still dispersed among an overwhelming number of non-target background cells. Here, we describe a protocol where we define a population of candidate target cells based on specific staining. Candidate cells are then isolated by laser microdissection and pressure catapulting (LMPC) and transferred onto a microliter reaction slide. This slide allows monitoring the single-cell isolation process and isothermal whole genome amplification in less than 2 MUL. The amplification products obtained from single cells can be forwarded to multiple analyses. PMID- 26374323 TI - Detection and Characterization of Circulating Tumor Cells by the CellSearch Approach. AB - Cancer metastasis occurs when cells shed from a primary or metastatic tumor, enter the circulation, and begin to grow in distant locations of the body. With current techniques it is possible to measure the presence of a few circulating tumor cells (CTC) in a blood sample. Detection of even the presence of a very small number (one or more) of these CTC in a 7.5 mL blood sample with the CellSearch system is associated with a significant decrease in survival of patients with metastatic carcinomas. The techniques and definitions used for the detection and enumeration of CTC with the CellSearch system were validated in series of preclinical and prospective multicenter studies. After enumeration of the CTC, the cells can be isolated from the cartridge for the purpose of downstream single-cell analysis. In this chapter, we will describe in detail the sample acquisition, sample preparation, data acquisition, and assignment of CTC used in the CellSearch system. PMID- 26374325 TI - Simulating Gram-Negative Bacterial Outer Membrane: A Coarse Grain Model. AB - The cell envelope of Gram-negative bacteria contains a lipopolysaccharide (LPS) rich outer membrane that acts as the first line of defense for bacterial cells in adverse physical and chemical environments. The LPS macromolecule has a negatively charged oligosaccharide domain that acts as an ionic brush, limiting the permeability of charged chemical agents through the membrane. Besides the LPS, the outer membrane has radially extending O-antigen polysaccharide chains and beta-barrel membrane proteins that make the bacterial membrane physiologically unique compared to phospholipid cell membranes. Elucidating the interplay of these contributing macromolecular components and their role in the integrity of the bacterial outer membrane remains a challenge. To bridge the gap in our current understanding of the Gram-negative bacterial membrane, we have developed a coarse grained force field for outer membrane that is computationally affordable for simulating dynamical process over physiologically relevant time scales. The force field was benchmarked against available experimental and atomistic simulations data for properties such as membrane thickness, density profiles of the residues, area per lipid, gel to liquid-crystalline phase transition temperatures, and order parameters. More than 17 membrane compositions were studied with a combined simulation time of over 100 MUs. A comparison of simulated structural and dynamical properties with corresponding experimental data shows that the developed force field reproduces the overall physiology of LPS rich membranes. The affordability of the developed model for long time scale simulations can be instrumental in determining the mechanistic aspects of the antimicrobial action of chemical agents as well as assist in designing antimicrobial peptides with enhanced outer membrane permeation properties. PMID- 26374326 TI - How does wrist position affect the length of the distal radioulnar ligament: a three-dimensional image study in vivo? AB - PURPOSE: This study was designed to investigate the length changes of the distal radioulnar ligament at different wrist positions and to determine the effect of hyperextension on the distal radioulnar ligament and to find out the most vulnerable position where the distal radioulnar ligament rupture and foveal avulsion. METHODS: We obtained computed tomography scans of the wrists for 12 volunteers including two groups: hyperextension group and hyperextension with maximal rotation group. The images were reconstructed to the three-dimensional bone structures with customized software. The four portions of the distal radioulnar ligament were measured and analyzed statistically. RESULTS: No significant differences were noted in the lengths of the each portion of the distal radioulnar ligament among neutral position, wrist hyperextension, and hyper-radial extension. From neutral position to hyperextension with maximal pronation, the lengths of the palmar superficial radioulnar ligament (psRU) and dorsal deep radioulnar ligament (ddRU) decreased significantly, whereas the dorsal superficial radioulnar ligaments (dsRU) and palmar deep radioulnar ligament (pdRU) increased significantly. From neutral position to hyperextension with maximal supination, the lengths of the pdRU and dsRU ligaments decreased significantly, and the lengths of psRU and ddRU ligaments changed little. CONCLUSIONS: The factor of hyperextension has little effect on the length of the distal radioulnar ligament and the distal radioulnar ligament may be under great tension at the position of hyperextension with maximal pronation. These findings can provide more information to understand the pathomechanics of the triangular fibrocartilage complex injury caused by a fall on the outstretched hand and can provide information relevant to the distal radioulnar ligament restoration. PMID- 26374324 TI - Natural killer cell receptors: alterations and therapeutic targeting in malignancies. AB - Numerous newly identified activating and inhibitory NK cell receptors and their engagement by cognate ligands on target tumor cells regulate NK cell antitumor activity. Alterations in NK cell receptor expression and signaling underlie diminished cytotoxic NK cell function. Cytokines, IFN-alpha, IL-2, IL-12, IL-15 and IL-18, applied systemically and for ex vivo activation and expansion of NK cells have improved NK cell antitumor activity by increasing the expression of NK cell activating receptors and by inducing cytotoxic effector molecules. Moreover, it has been recognized that classical and novel pharmacological agents upregulate cognate ligands for activating receptors on tumor cells and provide better NK cell antitumor response. Some other immunotherapeutic approaches in cancer in the setting of donor-recipient KIR/HLA mismatch have evolved with the aim to potentiate NK cell activity in allogeneic hematopoietic stem cell transplantation that lead to beneficial graft vs. tumor effect. Therefore, better understanding of NK cell activating and inhibitory receptor biology is needed to assist in developing novel approaches to effectively manipulate NK cells and create effective NK cell-based immunotherapy for treatment of cancer patients. PMID- 26374327 TI - Fosfomycin use in multi drug resistant uropathogenic Escherichia coli. AB - OBJECTIVES AND AIMS: Escherchia coli isolated, from urine samples were studied for their antibiotic susceptibility patterns, with special reference to the new antimicrobial compound fosfomycin and their correlation with various virulence factors. MATERIAL AND METHODS: The mid stream urine samples received in the department were processed and identification was done by using the standard culture and identification techniques. The antibiotic susceptibility testing was done by modified Kirby-Bauer disk diffusion and the disk diffusion method was used to confirm the ESBL, AmpC, MBL production by the UPEC. Various virulence factors like hemolysin, haemagglutinaton, gelatinase, siderophore production, biofilm formation, serum resistance and hydrophobicity were detected. RESULTS: Fosfomycin was found to be most effective agent (100%) against uropathogenic E.coli followed by netilmicin (89.5%). The least effective agents were ampiciilin and cotrimoxazole. Twenty nine percent (29%) isolates were found to be multi drug resistant (MDR). CONCLUSIONS: The testing of the newer therapeutic agents like fosfomycin will add on to therapeutics for UTI's. PMID- 26374328 TI - School Absenteeism: An Online Survey via Social Networks. AB - School absenteeism is a significant social and public health problem. However, existing prevalence rates are often not representative due to biased assessment processes at schools. The present study assessed school absenteeism in Germany using a nationwide online self-report survey. Although our definition of school absenteeism was more conservative than in previous studies, nearly 9 % of the 1359 high school students reported school absenteeism within the past 7 days. Absent students lived less often with both parents, were on average of lower socioeconomic status, and reported more emotional problems, behavioral problems and less prosocial behavior than attending students. Being an indicator of a wide variety of problems in children and adolescents, school absenteeism deserves much more attention. Future directions for research and implications for prevention and intervention programs are discussed. PMID- 26374329 TI - Transmission of ER stress response by ATF6 promotes endochondral bone growth. AB - BACKGROUND: We reported earlier that X-box binding protein1 spliced (XBP1S), a key regulator of the unfolded protein response (UPR), as a bone morphogenetic protein 2 (BMP2)-inducible transcription factor, positively regulates endochondral bone formation by activating granulin-epithelin precursor (GEP) chondrogenic growth factor. Under the stress of misfolded or unfolded proteins in the endoplasmic reticulum (ER), the cells can be protected by the mammalian UPR. However, the influence of activating transcription factor 6 (ATF6), another transcriptional arm of UPR, in BMP2-induced chondrocyte differentiation has not yet been elucidated. In the current study, we investigate and explore the role of ATF6 in endochondral bone formation, focus on associated molecules of hypertrophic chondrocyte differentiation, as well as the molecular events underlying this process. METHODS: High-cell-density micromass cultures were used to induce ATDC5 and C3H10T1/2 cell differentiation into chondrocytes. Quantitative real-time PCR, immunoblotting analysis, and immunohistochemistry were performed to examine (1) the expression of ATF6, ATF6alpha, collagen II, collagen X, and matrix metalloproteinase-13 (MMP13) and (2) whether ATF6 stimulates chondrogenesis and whether ATF6 enhances runt-related transcription factor 2 (Runx2)-mediated chondrocyte hypertrophy. Culture of fetal mouse bone explants was to detect whether ATF6 stimulates chondrocyte hypertrophy, mineralization, and endochondral bone growth. Coimmunoprecipitation was employed to determine whether ATF6 associates with Runx2 in chondrocyte differentiation. RESULTS: ATF6 is differentially expressed in the course of BMP2-triggered chondrocyte differentiation. Overexpression of ATF6 accelerates chondrocyte differentiation, and the ex vivo studies reveal that ATF6 is a potent stimulator of chondrocyte hypertrophy, mineralization, and endochondral bone growth. Knockdown of ATF6 via a siRNA approach inhibits chondrogenesis. Furthermore, ATF6 associates with Runx2 and enhances Runx2-induced chondrocyte hypertrophy. And, the stimulation effect of ATF6 is reduced during inhibition of Runx2 via a siRNA approach, suggesting that the promoting effect is required for Runx2. CONCLUSIONS: Our observations demonstrate that ATF6 positively regulates chondrocyte hypertrophy and endochondral bone formation through activating Runx2 mediated hypertrophic chondrocyte differentiation. PMID- 26374330 TI - Semantic and phonological contributions to short-term repetition and long-term cued sentence recall. AB - The function of verbal short-term memory is supported not only by the phonological loop, but also by semantic resources that may operate on both short and long time scales. Elucidation of the neural underpinnings of these mechanisms requires effective behavioral manipulations that can selectively engage them. We developed a novel cued sentence recall paradigm to assess the effects of two factors on sentence recall accuracy at short-term and long-term stages. Participants initially repeated auditory sentences immediately following a 14-s retention period. After this task was complete, long-term memory for each sentence was probed by a two-word recall cue. The sentences were either concrete (high imageability) or abstract (low imageability), and the initial 14-s retention period was filled with either an undemanding finger-tapping task or a more engaging articulatory suppression task (Exp. 1, counting backward by threes; Exp. 2, repeating a four-syllable nonword). Recall was always better for the concrete sentences. Articulatory suppression reduced accuracy in short-term recall, especially for abstract sentences, but the sentences initially recalled following articulatory suppression were retained better at the subsequent cued recall test, suggesting that the engagement of semantic mechanisms for short-term retention promoted encoding of the sentence meaning into long-term memory. These results provide a basis for using sentence imageability and subsequent memory performance as probes of semantic engagement in short-term memory for sentences. PMID- 26374331 TI - No source memory for unrecognized items when implicit feedback is avoided. AB - In a recent empirical study, Starns, Hicks, Brown, and Martin (Memory & Cognition, 36, 1-8 2008) collected source judgments for old items that participants had claimed to be new and found residual source discriminability depending on the old-new response bias. The authors interpreted their finding as evidence in favor of the bivariate signal-detection model, but against the two high-threshold model of item/source memory. According to the latter, NEW responses only follow from the state of old-new uncertainty for which no source discrimination is possible, and the probability of entering this state is independent of the old-new response bias. However, when missed old items were presented for source discrimination, the participants could infer that the items had been previously studied. To test whether this implicit feedback led to second retrieval attempts and thus to source memory for presumably unrecognized items, we replicated Starns et al.'s (Memory & Cognition, 36, 1-8 2008) finding and compared their procedure to a procedure without such feedback. Our results challenge the conclusion to abandon discrete processing in source memory; source memory for unrecognized items is probably an artifact of the procedure, by which implicit feedback prompts participants to reconsider their recognition judgment when asked to rate the source of old items in the absence of item memory. PMID- 26374333 TI - Laparoscopic mediastinal dissection via an open left diaphragm approach for advanced Siewert type II adenocarcinoma. AB - Around the lower esophagus, the diaphragm obstructs the laparoscopic dissection of mediastinal lymph nodes in surgery for Siewert type II cancer. To address this problem, we developed the open left diaphragm approach. After dissecting the esophageal hiatus along the diaphragm, the anterior mediastinum is dissected along the pericardium. The left side of the mediastinal pleura is then opened and the left diaphragm is incised with a 60-mm linear stapler to create sufficient working space in the lower mediastinum for the lower mediastinal lymph nodes to be resected with a good view. Six patients who received neoadjuvant chemotherapy underwent mediastinal dissection using this technique. The median operative time and estimated blood loss were 479 (390-750) min and 250 (130-500) ml, respectively, and there were no deaths or severe complications. The open left diaphragm approach provides clear surgical space and a good view for performing mediastinal lymph node dissection and is useful for laparoscopic mediastinal dissection and reconstruction. PMID- 26374334 TI - Differential IKK/NF-kappaB Activity Is Mediated by TSC2 through mTORC1 in PTEN Null Prostate Cancer and Tuberous Sclerosis Complex Tumor Cells. AB - The serine/threonine protein kinase Akt plays a critical role in regulating proliferation, growth, and survival through phosphorylation of different downstream substrates. The mTOR is a key target for Akt to promote tumorigenesis. It has been reported that Akt activates mTOR through phosphorylation and inhibition of the tuberous sclerosis complex (TSC) protein TSC2. Previously, it was demonstrated that mTOR activates IKK/NF-kappaB signaling by promoting IkappaB kinase (IKK) activity downstream of Akt in conditions deficient of PTEN. In this study, the mechanistic role of the tumor-suppressor TSC2 was investigated in the regulation of IKK/NF-kappaB activity in PTEN-null prostate cancer and in TSC2 mutated tumor cells. The results demonstrate that TSC2 inhibits IKK/NF-kappaB activity downstream of Akt and upstream of mTORC1 in a PTEN-deficient environment. However, TSC2 promotes IKK/NF-kappaB activity upstream of Akt and mTORC1 in TSC2 mutated tumor cells. These data indicate that TSC2 negatively or positively regulates IKK/NF-kappaB activity in a context-dependent manner depending on the genetic background. IMPLICATIONS: This study provides fundamental insight for understanding the molecular details by which TSC2/mTOR regulates NF-kappaB signaling in different tumors. PMID- 26374335 TI - Variability of postural orthostatic tachycardia in patients with myalgic encephalomyelitis and orthostatic intolerance. AB - Central nervous system dysfunction with myalgic encephalomyelitis (ME) has been suggested as the main cause of chronic fatigue syndrome. Fluctuation of the symptom severity and hierarchy is a characteristic feature in ME patients. The characteristics of the sympathetic activation may differ between the "good days" and "bad days" in them. Twenty-four ME patients with orthostatic intolerance underwent a conventional 10-min active standing test and echocardiography both on a "good day" and a "bad day", defined according to the severity of their symptoms. The mean heart rate at rest was significantly higher on the "bad days" than on the "good days". During the standing test on a "bad day", 5 patients (21 %) failed to maintain an upright posture for 10 min, whereas on a "good day" all the 24 patients maintained it. Postural orthostatic tachycardia (POT) (increase in heart rate >=30 beats/min) or severe POT (heart rate >=120 beats/min) was observed on the "bad days" in 10 patients (43 %) who did not suffer from the severe tachycardia on the "good days", suggesting the exaggerated sympathetic nervous activation. In contrast, POT did not occur or severe POT was attenuated on the "bad days" in 5 patients (21 %) who developed POT or severe POT on the "good days", suggesting the impaired sympathetic activation. Echocardiography revealed significantly lower mean values of both the left ventricular end diastolic diameter and stroke volume index on the "bad days" compared with the "good days". In conclusion, in ME patients with orthostatic intolerance, the exaggerated activation of the sympathetic nervous system while standing appears to switch to the impaired sympathetic activation after the system is loaded with the additional accentuated stimuli associated with the preload reduction. PMID- 26374337 TI - [Thromboprophylaxis in the critically ill : Low molecular weight heparin versus unfractionated heparin]. PMID- 26374338 TI - [Patients' declared intentions and emergency medicine]. AB - Patients with complex medical problems and acute life-threatening diseases deserve a physician with the capability of rapid decision making. Despite an emergency scenario with several unknown or uncertain variables an individual therapeutic plan needs to be defined for each patient. In order to achieve this goal the physician must define medical indications for each form of treatment. Secondly, the patients declared intentions must be respected concerning the previously defined medical indications; however, very often the patients' will is not known. It is very difficult to define an individual treatment plan especially if the patient is not able to adequately communicate. In these situations a custodian is helpful to find out the patients declared intentions towards the current medical situation. If there is no advance directive, family members often have to act as surrogates to find out what therapy goal is best for the individual patient. The patients' autonomy is a very highly respected ethical priority even when the ability for the otherwise usual practice of shared decision-making between physician and patient is compromised. Therefore, in order to do justice to this demanding situation it is necessary to deal with the characteristics of the physician-patient-relatives relationship in emergency medicine. PMID- 26374336 TI - Organization of junctional sarcoplasmic reticulum proteins in skeletal muscle fibers. AB - The sarcoplasmic reticulum (SR) of striated muscles is specialized for releasing Ca(2+) following sarcolemma depolarization in order to activate muscle contraction. To this end, the SR forms a network of longitudinal tubules and cisternae that surrounds the myofibrils and, at the same time, participates to the assembly of the triadic junctional membrane complexes formed by the close apposition of one t-tubule, originated from the sarcolemma, and two SR terminal cisternae. Advancements in understanding the molecular basis of the SR structural organization have identified an interaction between sAnk1, a transmembrane protein located on the longitudinal SR (l-SR) tubules, and obscurin, a myofibrillar protein. The direct interaction between these two proteins results in molecular contacts that have the overall effect to stabilize the l-SR tubules along myofibrils in skeletal muscle fibers. Less known is the structural organization of the sites in the SR that are specialized for Ca(2+) release and are positioned at the junctional SR (j-SR), i.e. the region of the terminal cisternae that faces the t-tubule at triads. At the j-SR, several trans-membrane proteins like triadin, junctin, or intra-luminal SR proteins like calsequestrin, are assembled together with the ryanodine receptor, the SR Ca(2+) release channel, into a macromolecular complex specialized in releasing Ca(2+). At triads, the 12 nm-wide gap between the t-tubule and the j-SR allows the ryanodine receptor on the j-SR to be functionally coupled with the voltage-gated L-type calcium channel on the t-tubule in order to allow the transduction of the voltage induced signal into Ca(2+) release through the ryanodine receptor channels. The muscle-specific junctophilin isoforms (JPH1 and JPH2) are anchored to the j-SR with a trans-membrane segment present at the C-terminus and are capable to bind the sarcolemma with a series of phospholipid-binding motifs localized at the N terminus. Accordingly, through this dual interaction, JPH1 and JPH2 are responsible for the assembly of the triadic junctional membrane complexes. Recent data indicate that junctophilins seem also to interact with other proteins of the excitation-contraction machinery, suggesting that they may contribute to hold excitation-contraction coupling proteins to the sites where the j-SR is being organized. PMID- 26374339 TI - Effect of the laryngeal tube on the no-flow-time in a simulated two rescuer basic life support setting with inexperienced users. AB - INTRODUCTION: Intubation with a laryngeal tube (LT) is a recommended alternative to endotracheal intubation during advanced life support (ALS). LT insertion is easy; therefore, it may also be an alternative to bag-mask ventilation (BMV) for untrained personnel performing basic life support (BLS). Data from manikin studies support the influence of LT on no-flow-time (NFT) during ALS. METHODS: We performed a prospective, randomized manikin study using a two-rescuer model to compare the effects of ventilation using a LT and BMV on NFT during BLS. Participants were trained in BMV and were inexperienced in the use of a LT. RESULTS: There was no significant difference in total NFT with the use of a LT and BMV (LT: mean 83.1 +/- 37.3 s; BMV: mean 78.7 +/- 24.5 s; p = 0.313), but we found significant differences in the progression of the scenario: in the BLS scenario, the proportion of time spent performing chest compressions was higher when BMV was used compared to when a LT was used. The quality of chest compressions and the ventilation rate did not differ significantly between the two groups. The mean tidal volume and mean minute volume were significantly larger with the use of a LT compared with the use of BMV. CONCLUSIONS: In conclusion, in a two-rescuer BLS scenario, NFT is longer with the use of a LT (without prior training) than with the use of BMV (with prior training). The probable reasons for this result are higher tidal volumes with the use of a LT leading to longer interruptions without chest compressions. PMID- 26374340 TI - First-Line Treatment of Metastatic Colorectal Cancer: Interpreting FIRE-3, PEAK, and CALGB/SWOG 80405. AB - The advances made in the therapeutic management of colorectal cancer (CRC) over recent years with the addition of therapies targeting angiogenesis or cell proliferation have positioned bevacizumab, cetuximab, and panitumumab as accepted first-line treatments when combined with FOLFOX or FOLFIRI for RAS wild-type (WT) metastatic CRC. The question has been raised as to the choice of targeted therapy to maximize chances of an optimal outcome. Three studies, the phase III FIRE-3 (AIO KRK-0306), the phase II PEAK, and the recently presented phase III CALGB/SWOG 80405 trial, have addressed this issue face-on, directly comparing the addition of bevacizumab versus cetuximab or panitumumab to FOLFOX/FOLFIRI in terms of efficacy outcomes. None of these studies met their primary endpoint (response rate, progression-free survival or overall survival respectively), meaning we are no closer to being able to categorically define an optimal targeted treatment in the first-line setting for patients with advanced CRC. This led to reflection over study design and further analyses, raising a number of important issues. High-sensitivity analysis of the mutational status of exons identified a population with a "pure" non-RAS-mutated profile showing benefit with anti-epidermal growth factor receptor (anti-EGFR) combinations, particularly in the context of early and greater depth of response. Coherent with a personalized therapeutic approach, the importance of performing individual high sensitivity extended RAS testing is unequivocal and is currently a requirement in many countries to identify this all-RAS WT population, thus limiting unnecessary exposure and expense in patients unlikely to respond. These three studies, particularly the CALGB/SWOG 80405 trial, mark an important milestone in the roadmap of metastatic CRC treatment, highlighting the need for close analysis to fully exploit the available data. PMID- 26374342 TI - Differences in metabolism of the marine biotoxin okadaic acid by human and rat cytochrome P450 monooxygenases. AB - The ingestion of seafood contaminated with the marine biotoxin okadaic acid (OA) can lead to diarrhetic shellfish poisoning with symptoms like nausea, vomiting and abdominal cramps. Both rat and the human hepatic cytochrome P450 monooxygenases (CYP) metabolize OA. However, liver cell toxicity of metabolized OA is mainly unclear. The aim of our study was to detect the cellular effects in HepG2 cells exposed to OA in the presence of recombinant CYP enzymes of both rat and human for the investigation of species differences. The results should be set in correlation with a CYP-specific metabolite pattern. Comparative metabolite profiles of OA after incubation in rat and human recombinant CYP enzymes were established by using LC-MS/MS technique. Results demonstrated that metabolism of OA to oxygenated metabolites correlates with detoxification which was mainly catalyzed by human CYP3A4 and CYP3A5. Detoxification by rat Cyp3a1 was lower compared to human CYP3A enzymes and activation of OA by Cyp3a2 was observed, coincident with minor overall conversion capacity of OA. By contrast human and rat CYP1A2 seem to activate OA into cytotoxic intermediates. In conclusion, different mechanisms of OA metabolism may occur in the liver. At low OA doses, the human liver is likely well protected against cytotoxic OA, but for high shellfish consumers a potential risk cannot be excluded. PMID- 26374343 TI - 7th International conference on Tumor Microenvironment: Progression, Therapy& Prevention Tel Aviv, Israel October 11 -15, 2015. PMID- 26374341 TI - Review of Recommended Treatment of Uterine Carcinosarcoma. AB - Surgery is the primary treatment for uterine carcinosarcoma (UCS). Lymphadenectomy should be performed for staging purposes in tumors apparently confined to the uterus. Most studies found that lymphadenectomy is of therapeutic value. The therapeutic value of cytoreduction to no residual macroscopic disease in advanced UCS is based mostly on small retrospective uncontrolled studies. Postoperative adjuvant therapy should be considered for all stages of UCS. Adjuvant pelvic radiotherapy may reduce locoregional recurrences. However, this does not translate into improved overall survival since most recurrences are distant outside the irradiated field, and the survival rates remain poor, the 5 year overall survival being about 50%. Several adjuvant platin-based combination chemotherapy schedules such as cisplatin/ifosfamide, ifosfamide/paclitaxel, and paclitaxel/carboplatin have been found to be an effective mode of adjuvant treatment. Multimodal therapy (i.e., adjuvant chemotherapy plus radiotherapy) has also been shown to be effective. Most studies dealing with adjuvant treatment are retrospective and prospective randomized controlled trials (i.e., phase III studies) comparing that between the various adjuvant chemotherapy schedules and between them and multimodal treatment are lacking. Quality of life with the various treatment modalities needs also to be assessed. An effective targeted therapy has so far not been found. In spite of the multiple studies with regard to the treatment of UCS published during the last 15 years, the optimal management of UCS is still not established. PMID- 26374344 TI - Prenatal antidepressant exposure and child behavioural outcomes at 7 years of age: a study within the Danish National Birth Cohort. AB - OBJECTIVE: To investigate the impact of prenatal antidepressant exposure on behavioural problems in children at 7 years of age. DESIGN: Nationwide population based study. SETTING: Danish National Birth Cohort. POPULATION: A cohort of 49 178 pregnant women recruited between 1996 and 2002. METHODS: Data obtained from computer-assisted telephone interviews twice during pregnancy were used to identify children born to: (i) depressed women who took antidepressants during pregnancy (n = 210); (ii) depressed women who did not take any antidepressants during pregnancy (n = 231); and (iii) healthy women who were not depressed (n = 48 737). Childhood behavioural problems at 7 years of age were examined using the validated Danish parent-report version of the Strengths and Difficulties Questionnaire (SDQ). MAIN OUTCOME MEASURES: SDQ scores. RESULTS: No associations were observed between prenatal antidepressant exposure and abnormal SDQ scores for overall problem behaviour (adjusted relative risk, aRR 1.00; 95% confidence interval, 95% CI 0.49-2.05), hyperactivity/inattention (aRR 0.99; 95% CI 0.56 1.75), or peer problems (aRR 1.04; 95% CI 0.57-1.91). Although prenatal antidepressant exposure appeared to be associated with abnormal SDQ scores on the subscales of emotional symptoms (aRR 1.68; 95% CI 1.18-2.38) and conduct problems (aRR 1.58; 95% CI 1.03-2.42), these associations were significantly attenuated following adjustment for antenatal mood status (aRR 1.20; 95% CI 0.85-1.70 and aRR 1.19; 95% CI 0.77 1.83, respectively). Untreated prenatal depression was associated with an increased risk of all behavioural outcomes evaluated, compared with unexposed children, with significant attenuation following adjustment for antenatal mood status. CONCLUSIONS: The results of this study suggest that independent of maternal illness, prenatal antidepressant exposure is not associated with an increased risk of behavioural problems in children at 7 years of age. TWEETABLE ABSTRACT: Prenatal antidepressant exposure is not associated with an increased risk of child behavioural problems. PMID- 26374345 TI - 'Providing good and comfortable care by building a bond of trust': nurses views regarding their role in patients' perception of safety in the intensive care unit. AB - AIMS AND OBJECTIVES: To describe and understand intensive care unit (ICU) nurses' views regarding their role in ICU patients' perception of safety. BACKGROUND: Feeling safe is an important issue for ICU patients. Not feeling safe may result in adverse effects including traumatic experiences, having nightmares and feeling depressed. Nursing care plays a major role in patients' perception of safety. However, it is unknown whether ICU nurses are aware of this role. DESIGN: A grounded theory approach following Corbin and Strauss. METHODS: A total of 13 participants were included in the study following maximum variation sampling, by selecting ICU nurses who differed in gender, age, work experience as registered ICU nurse, and were employed in different IC units. In-depth interviews were performed using open-ended questions guided by a topic list with broad question areas. Data collection and analysis were executed during an iterative process. RESULTS: The core category, building a bond of trust to provide good and comfortable care, arose from four main categories: explaining and informing ICU patients, using patients' family bond, ICU nurses' attitudes and expertise, and creating physical safety. CONCLUSION: The ICU nurses stated that they were not explicitly aware of ICU patients' perception of safety, but that they strived to provide good and comfortable care, through building a bond of trust with their patients. According to the nurses, a bond of trust is essential for patients to feel safe in the ICU. RELEVANCE TO CLINICAL PRACTICE: The importance of feeling safe in ICU patients should be addressed within the education and clinical practice of ICU nurses, to ensure that they become aware of ICU patients' perception of safety. PMID- 26374346 TI - Government's move to cut red tape is impeding public health measures, say charities. PMID- 26374347 TI - Developmental plasticity and evolution--quo vadis? AB - The role of developmental (phenotypic) plasticity in ecology and evolution is receiving a growing appreciation among the biologists, and many plasticity specific concepts have become well established as part of the mainstream evolutionary biological thinking. In this essay, I posit that despite this progress several key perspectives in developmental plasticity remain remarkably traditional, and that it may be time to re-evaluate their continued usefulness in the face of the available evidence as the field looks to its future. Specifically, I discuss the utility of viewing plastic development as ultimately rooted in genes and genomes, and investigate the common notion that the environment--albeit a critical source of information--nevertheless remains passive, external to and separable from the organism responding to it. I end by highlighting conceptual and empirical opportunities that may permit developmental plasticity research to transcend its current boundaries and to continue its contributions toward a holistic and realistic understanding of organismal development and evolution. PMID- 26374349 TI - Missing the obvious: psychosocial obstacles in Veterans with hepatocellular carcinoma. AB - BACKGROUND: Socioeconomic disparities in patients with hepatocellular carcinoma (HCC) influence medical treatment. In addition to socioeconomic barriers, the Veteran population suffers from significant psychosocial obstacles. This study identifies the social challenges that Veterans face while undergoing treatment for HCC. METHODS: One hundred Veterans at the Palo Alto VA treated for HCC from 2009 to 2014 (50 consecutive patients who underwent a surgical procedure; 50 treated with intra-arterial therapy) were retrospectively reviewed. RESULTS: Substance abuse history was identified in 96%, and half were unemployed. Most patients survived on a limited income [median $1340, interquartile range (IQR) 900-2125]; 36% on <= $1000/month, 37% between $1001-2000/month and 27% with >$2000/month. A history of homelessness was found in 30%, more common in those of the lowest income (57% of <=$1K/month group, 23% of $1-2K/month group and 9% of >$2K/month group, P < 0.01). Psychiatric illness was present in 64/100 patients; among these the majority received ongoing psychiatric treatment. Transportation was provided to 23% of patients who would otherwise have been unable to attend medical appointments. CONCLUSIONS: Psychiatric disease and substance abuse are highly prevalent among Veterans with HCC. Most patients survive on a very meager income. These profound socioeconomic and psychosocial problems must be recognized when providing care for HCC to this population to provide adequate treatment and surveillance. PMID- 26374350 TI - Insulin-Like Growth Factor I Produces an Antidepressant-Like Effect and Elicits N Methyl-D-Aspartate Receptor Independent Long-Term Potentiation of Synaptic Transmission in Medial Prefrontal Cortex and Hippocampus. AB - BACKGROUND: Growth factors play an important role in regulating neurogenesis and synapse formation and may be involved in regulating the antidepressant response to conventional antidepressants. To date, Insulin-like growth factor I (IGFI) is the only growth factor that has shown antidepressant properties in human clinical trials. However, its mechanism of action remains unclear. METHODS: The antidepressant-like effect of a single IV dose of IGFI was determined using a chronic unpredictable stress paradigm in the rat Porsolt, sucrose preference, novelty-induced hypophagia, and ultrasonic vocalization models. The dependence of the medial prefrontal cortex for these effects was determined by direct medial prefrontal cortex injection followed by Porsolt testing as well as IGFI receptor activation in the medial prefrontal cortex following an optimal IV antidepressant like dose of IGFI. The effect of IGFI on synaptic transmission and long-term potentiation (LTP) of synaptic strength was assessed in the hippocampus and medial prefrontal cortex. The dependence of these effects on IGFI and AMPA receptor activation and protein synthesis were also determined. RESULTS: IGFI produced a rapid-acting and long-lasting antidepressant-like effect in each of the depression models. These effects were blocked by IGFI and AMPA receptor antagonists, and medial prefrontal cortex was localized. IGFI robustly increased synaptic strength in the hippocampus and medial prefrontal cortex and these effects were IGFI receptor and protein synthesis-dependent but N-methyl-d aspartate receptor independent. IGFI also robustly facilitated hippocampal metaplasticity 24 hours postdosing. CONCLUSIONS: These data support the conclusion that the antidepressant-like effects of IGFI are mediated by a persistent, LTP-like enhancement of synaptic strength requiring both IGFIR activation and ongoing protein synthesis. PMID- 26374355 TI - Should Hepatitis B be Biopsied? PMID- 26374351 TI - Variants of the scimitar syndrome. AB - Introduction The scimitar syndrome comprises hypoplastic right pulmonary artery and lung, anomalous right pulmonary venous drainage to the inferior caval vein, aortopulmonary collateral(s) to the right lung, and bronchial anomalies. Aim The aim of this study was to describe the morphological and clinical spectrum of variants from the classical scimitar syndrome in a single institution over 22 years. RESULTS: In total, 10 patients were recognised. The most consistent feature was an aortopulmonary collateral to the affected lung (90%), but there was considerable variation in the site and course of pulmonary venous drainage. This was normal in 3 (one with meandering course), anomalous right to superior caval vein in 1, to the superior caval vein and inferior caval vein in 2, and to the superior caval vein and the left atrium in 1; one patient had a right pulmonary (scimitar) vein occluded at the insertion into the inferior caval vein but connected to the right upper pulmonary vein via a fistula. There were two left-sided variants, one with anomalous left drainage to the coronary sinus and a second to the innominate vein. Among all, three patients had an antenatal diagnosis and seven presented between 11 and 312 months of age; 90% of the patients were symptomatic at first assessment. All the patients underwent cardiac catheterisation; collateral embolisation was performed in 50% of the patients. Surgical repair of the anomalous vein was carried out in two patients, one patient had a right pneumonectomy, and one patient was lost to follow-up. There was no mortality reported in the remainder of patients during the study period. CONCLUSION: The heterogeneity of this small series confirms the consistent occurrence of an anomalous arterial supply to the affected lung but considerable variation in pulmonary venous drainage. PMID- 26374356 TI - Clinical Safety and Parameters of Maximum Oxygen Uptake (VO2Max) Testing in Pakistani Patients With Heart Failure. AB - OBJECTIVE: To determine the parameters of maximum oxygen uptake (VO2max) in a Pakistani systolic heart failure cohort and its safety in a clinical setting. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Armed Forces Institute of Cardiology, National Institute of Heart Diseases, Rawalpindi, from June 2011 to January 2013. METHODOLOGY: Maximum oxygen uptake test was performed in patients with severe heart failure, who could perform the VO2max treadmill test. Age, Body Mass Index (BMI) ejection fraction, VO2max and respiratory exchange ratios and their correlations were determined. RESULTS: Out of 135 patients, 77% (n=104) were males, with a mean age of 45.9 +/-15.7 years. Weight of patients ranged from 30 kg to 107 kg (mean 63.29 +/-13.6 kg); mean BMI was 23.16 +/-4.56 kg/m2. All patients presented with either NYHA class of III (50.3%; n=68) or IV (49.7%; n=67); mean ejection fraction was 22.54 +/-5.7% (10 - 35%, IQ:20 - 25). The VO2 max of the patients ranged from 3 to 32 ml/kg/minute (mean 12.85 +/-4.49 ml/kg/minute). Respiratory exchange ratio was over 1 for all patients (1.12 - 1.96, mean = 1.36 +/-0.187). There was a negative correlation with age (r = -0.204; p = 0.028) whereas a positive correlation was found with exercise time (r = 0.684; p = 0.000), hemoglobin (r = 0.190; p = 0.047) and ejection fraction (r = 0.187 ; p = 0.044). CONCLUSION: Cardiopulmonary exercise testing in a high-risk heart failure cohort is safe and provides information beyond the routine clinical evaluation of heart failure patients. PMID- 26374357 TI - Association Between Polymorphism in the Human Cathepsin L (CTSL1) Promoter with Hypertension in the Uygur, Kazak and Han Populations in China. AB - OBJECTIVE: To systemically investigate the association between the polymorphism (rs3118869) in cathepsin Lenzyme gene with hypertension in three ethnic groups (Han, Kazak and Uygur) in China. STUDY DESIGN: Case-control study. PLACE AND DURATION OF STUDY: Department of Cardiology, The First Affiliated Hospital, Shihezi Medical College, Shihezi University and Department of Internal Medicine and Genetic Diagnosis Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, from January 2013 to May 2014. METHODOLOGY: This case-control study included 1224 patients (422 Uygur, 425 Kazak and 377 Han individuals) with hypertension and 967 healthy unrelated individuals (339 Uygur, 337 Kazak and 291 Han individuals) as controls. The participants came from three ethnic groups (Han, Kazak and Uygur) which were recruited from Xinjiang Province of China. The polymorphism (rs3118869) of the human cathepsin Lgene was genotyped using the TaqMan 5' nuclease assay. Binary logistic regression was built to determine the association of polymorphism with hypertension. RESULTS: The genotype distribution of polymorphism was not significantly different in three ethnic groups. The rs3118869 polymorphism was significantly associated with Essential Hypertension (EH) in co-dominant model (A/C vs. C/C) in total people (OR = 0.697, 95% CI = 0.520 -0.932, p = 0.015), the same result was obtained in recessive model (C/C + A/C vs. A/A) in total people (OR = 0.689, 95% CI = 0.522 0.910, p = 0.009). Similar finding of rs3118869 in recessive model (C/C + A/C vs. A/A) was also observed after adjusting the variable to the covariates age (OR = 0.629, 95% CI = 0.464 0853, p = 0.003). CONCLUSION: The study results indicate the A-allele of rs3118869 is a protective factor in hypertension. PMID- 26374358 TI - Hereditary Hemochromatosis. AB - OBJECTIVE: To describe the clinical and laboratory features of hereditary hemochromatosis associated liver disease in a tertiary care hospital. STUDY DESIGN: Observational study. PLACE AND DURATION OF STUDY: The Aga Khan University Hospital, Karachi, from January 2002 to October 2012. METHODOLOGY: Charts of patients with Hereditary Hemochromatosis (HHC) were reviewed. Data collected and analyzed consisting of clinical presentations, liver function tests, serum ferritin, transferrin saturation, hepatic imaging and histology in patients with HHC. RESULTS: A total of 22 patients were identified as having hemochromatosis. All subjects were men with a mean age of 53 +/-9.2 years at the time of diagnosis. The most common presentation was skin pigmentation seen in 17 (77%), followed by loss of libido/ impotence in 11 (50%) and then arthralgias in 10 (45%) and weakness in 6 (27%). Eleven (50%) subjects had diabetes mellitus and one subject had concomitant cardiac involvement. Patients with diabetes were diagnosed earlier as compared to those without it. Eighteen (81%) subjects had cirrhosis at the time of diagnosis. Serum iron was 164 +/-53 ug/dl, ferritin 3391 +/-1960 ug/L, TIBC 202 +/-61 ug/dl and transferrin saturation 76.8 +/-14%. Liver biopsy was done in 10 (45%) and using Pearls' stain histopathological features were consistent with hemochromatosis and none had carcinoma. Only 3 (14%) patients had regular phlebotomy. CONCLUSION: Hemochromatosis is not a rare disease in Pakistan and should be looked in those subjects whose liver function tests are deranged. PMID- 26374359 TI - Predicting Prognosis in Hepatocellular Carcinoma: Comparison of Staging Systems in Pakistani Cohort. AB - OBJECTIVE: To determine the clinical, biochemical and radiological prognostic indicators and to compare the performance of six staging systems in patients of hepatocellular carcinoma (HCC). STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Department of Gastroenterology, Doctors Hospital, Lahore, from October 2007 to December 2013. METHODOLOGY: Patients with HCC were included. Baseline clinical, hematological and radiological variables were noted. Patients were followed for 5 years or till death. Survival predictors were identified using Cox proportional hazard analysis and 6 prognostic staging systems were evaluated by determining homogeneity, discriminatory ability and monotonicity. RESULTS: Of the 228 patients included, male to female ratio was 2.6/1 (165/63) and mean age was 56.5 +/-10.4 years. Majority of patients 189 (82.9%) were anti HCV positive. Solitary HCC lesion was seen in 121 (53.1%) patients, 16 (7%) had 2 lesions while 73 (32%) had 3 or more lesions. Only 36 (15.8%) patients had palliative therapy for HCC. Survival rate was 45.2%, 25%, 12.3%, 7%, 2.2% and 1% for 6 months, 1, 2, 3, 4 and 5 years respectively. Male gender, portal vein thrombosis, serum albumin < 3.5 g/dl, tumor size >=6 cm and alpha fetoprotein (AFP) >=147 U/ml were bad prognostic indicators. OKUDA, GRETCH and early stages of CLIP had better homogeneity while CLIP showed superior discriminatory ability and monotonicity for predicting survival. CONCLUSION: Male gender, presence of portal vein thrombosis, low serum albumin, large tumor size and high AFP level are poor prognostic indicators in patients of HCC. CLIP has better performance in predicting mortality. PMID- 26374360 TI - Morphological Variants of Renal Carcinoma in Radical Nephrectomy Specimens. AB - OBJECTIVE: To determine the morphological variants of Renal Cell Carcinoma (RCC) to detect the commonest histopathological type with special focus to the newly introduced entity Clear Cell Papillary Renal Cell Carcinoma (CCPRCC). STUDY DESIGN: Case series. PLACE AND DURATION OF STUDY: Department of Pathology, Basic Medical Sciences Institute, JPMC, Karachi, from January 2007 to December 2012. METHODOLOGY: Paraffin embedded blocks of 32 cases of radical nephrectomy specimens for renal mass were selected from records of Pathology Department, BMSI. Cases were excluded due to inadequate biopsies. Remaining 30 cases of renal cell carcinoma were included in study. H & E staining was done for all cases and PAS stain was employed for a few cases. All cases were reviewed under light microscope. RESULTS: The 30 cases of renal cell carcinoma included 21 (70%) clear cell renal cell carcinoma, 03 (10%) clear cell papillary renal cell carcinoma, 02 (6.6%) papillary renal cell carcinoma and 04 (13.33%) hybrid tumors. Majority of cases (53.3%) found in age range between 40 - 60 years while 23.33% cases were found in 7th and 6.6% in 8th decade of life. While 16.66% cases were in younger age group that is between 31 - 40 years of age. Sixty percent cases of right radical nephrectomies and 40% cases of left radical nephrectomies. CONCLUSION: CCRCC was most common histopathologic type followed by CCPRCC, hybrid tumors and PRCC. PMID- 26374361 TI - Lymphangioma Circumscriptum: Clinicopathological Spectrum of 29 Cases. AB - OBJECTIVE: To describe the clinicopathological spectrum of Lymphangioma Circumscriptum (LC). STUDY DESIGN: Observational case series. PLACE AND DURATION OF STUDY: Department of Pathology and Microbiology, AKUH, Karachi, from 2002 to 2012. METHODOLOGY: All reported cases of LC were retrieved from medical record. Clinical and pathological features were noted. Frequency percentages were determined. RESULTS: There were 29 cases of LC predominantly males (62%). The mean age was 27.17 +/-15.5 years. The commonest sites was anal/perianal region (24%) followed by extremities (17%) and tongue, (14%). Vulval LC was seen in 3 patients. Two cases were described on scrotum. The lesions were most commonly suspected as viral warts, mole or polyp (in anal region). Vesicles with erosions and bleeding and localized growth were the usual clinical presentations. Four of the patients presented with swelling since birth. All were treated with surgical excision. Microscopic examination revealed acanthotic squamous epithelium with papillomatosis. The subepithelial region had collections of lymphatic channels composed of ectatic dilated vessels with serum and inflammatory cells in their lumina. The lymphatic channels were seen in deeper layers along with lymphocytic aggregates. CONCLUSION: Lymphangioma circumscriptum is a malformation of abnormal lymphatic channels with feeding cisterns in subcutaneous tissue. It is a benign lesion usually occurring in anal/perianal region and confused with warts. Surgical excision is preferred mode of treatment. PMID- 26374362 TI - Early Diagnosis of Typhoid By PCR For FliC-d Gene of Salmonella Typhi in Patients Taking Antibiotics. AB - OBJECTIVE: To compare PCR (Polymerase Chain Reaction) with blood culture, typhi dot and Widal test for the diagnosis of typhoid in patients taking antibiotics. STUDY DESIGN: Cross-sectional, comparative study. PLACE AND DURATION OF STUDY: National University of Sciences and Technology, Islamabad, Pakistan, from April 2013 to August 2014. METHODOLOGY: One hundred and five patients were included in the study. Blood was collected and inoculated into tryptone soya broth for culture. Any growth obtained was identified by API 20 E and confirmed by Salmonella anti-sera. Typhi-dot and Widal test were also done on all the samples. DNA extraction was done and PCR was carried out. RESULTS: Among the 105 patients, 79 (75.2%) were males and 26 (24.8%) were females, with mean age of 20.64 +/-14 years. Typhi-dot was positive in 58 (55.2%) and negative in 47 (44.8%) patients. Blood widal test was positive in 27 (25.7%) and negative in 78 (74.3%) patients. Salmonella Typhi was positive on blood culture in only one (1%) patient. PCR for Salmonella Typhi was positive in 102 (97.1%) and negative in 3 (2.9%) patients. Positive cases detected by PCR were significantly higher as compared to Typhi-dot (p < 0.001), blood Widal test (p < 0.001) and blood culture (p < 0.001). CONCLUSION: Positivity rate of PCR was significantly higher as compared to blood culture, Typhi-dot or Widal test for diagnosing typhoid in patients who were already taking antibiotics. PMID- 26374363 TI - Umbilical Cord Blood pH in Intrapartum Hypoxia. AB - OBJECTIVE: To determine the association of cord arterial blood pH with neonatal outcome in cases of intrapartum fetal hypoxia. STUDY DESIGN: Descriptive analytical study. PLACE AND DURATION OF STUDY: Gynaecology Unit-II, Civil Hospital, Karachi, from September 2011 to November 2012. METHODOLOGY: All singleton cephalic fetuses at term gestation were included in the study. Those with any anomaly, malpresentation, medical disorders, maternal age < 18 years, multiple gestation and ruptured membranes were excluded. Patients with abnormal cardiotocography and/or meconium stained liquor were enrolled as index case and immediate next delivery with no such signs as a control. Demographic characteristics, pH level < or > 7.25, neonatal outcome measures (healthy, NICU admission or neonatal death), color of liquor and mode of delivery recorded on predesigned proforma. Statistical analysis performed by SPSS 16 by using independent-t test or chi-square test and ANOVA test as needed. RESULTS: A total of 204 newborns were evaluated. The mean pH level was found to be significantly different (p=0.007) in two groups. The pH value 7.25 had significant association (p < 0.001) with the neonatal outcome. However, the association of neonatal outcome with severity of acidemia was not found to be significant. Grading of Meconium Stained Liquor (MSL) also did not relate positively with pH levels as 85.7% of grade I, 68.9% of grade II and 59.4% of grade III MSLhad pH > 7.25. Majority (63.6%) cases needed caesarean section as compared to 31.4% controls. CONCLUSION: There is a significant association of cord arterial blood pH at birth with neonatal outcome at pH < or > 7.25; but below the level of pH 7.25 it is still inconclusive. PMID- 26374364 TI - Serum IgE Levels: An Effective Diagnostic Tool for Evaluation and Monitoring of Orbital Fungal Granuloma. AB - OBJECTIVE: To determine the changes in IgE levels in diagnosis and postoperative monitoring of orbital fungal granuloma. STUDY DESIGN: Descriptive analytical study. PLACE AND DURATION OF STUDY: Al-Shifa Trust Eye Hospital, Rawalpindi, Pakistan, from July 2012 to June 2013. METHODOLOGY: Cases with clinically high index of suspicion for orbital fungal granuloma and 50 healthy volunteers were inducted as control subjects. Patients with recurrent cases of orbital fungal granuloma, previous orbital surgery, and those with very low clinical suspicion of fungal granuloma were excluded. Total serum IgE level (IU/ml), eosinophil counts and skin prick test were performed in all subjects. Independent t-test was used for comparison of healthy volunteers and patients with biopsy proven orbital fungal granuloma. Repeated measures ANOVA was used for comparing the preoperative and postoperative total serum IgE level of patients with biopsy proven fungal granuloma. RESULTS: The mean total serum IgE level for the healthy volunteers was 208.82 +/-41.43 IU/ml. The mean pre-operative IgE value of histologically confirmed cases of fungal granuloma was 1613.72 +/-282.83 IU/ml. The total serum IgE level gradually declined after surgery and anti-fungal treatment. The mean serum IgE level 3, 6 and 9 months postoperatively were 1039.48 +/-308.40, 568.77 +/-162.01 and 224.92 +/-51.55 IU/ml respectively. These tests showed that the drop in IgE level in cases of fungal granuloma with treatment was statistically significant (p < 0.001). CONCLUSION: Total serum IgE level can be used as a reliable diagnostic and postoperative monitoring tool in orbital fungal granuloma. PMID- 26374365 TI - The Trauma of Sexual Harassment and its Mental Health Consequences Among Nurses. AB - OBJECTIVE: To determine the prevalence of sexual harassment in nurses and to observe its correlation with negative mental health (depression, anxiety and stress). Further to examine the role of sexual harassment as a predictor of negative mental health in nurses and to explore the differences in the experience of sexual harassment, depression, anxiety and stress between junior and senior nurses. STUDY DESIGN: Cross-sectional descriptive study. PLACE AND DURATION OF STUDY: Public Sector Hospitals in Lahore, from December 2011 to March 2012. METHODOLOGY: Asample of 200 nurses with age range 23 to 46 years was obtained. Assessment tools used in the study were Sexual Harassment Experience Questionnaire (SHEQ) by Kamal, and Depression, Anxiety and Stress Scale (DASS) by Lovibond and Lovibond. RESULTS: Mean age of the nurses was 29.80 +/-7.10 years. Among these 63% were married and 37% unmarried. The mean working experience of nurses was 13.7 +/-3. 52 years and their mean monthly income was 27820 +/ 13687.32 rupees. Their working hours ranged from 8 to 16 hours (M = 8.32, SD = 2.12). The mean prevalence of sexual harassment was 71.66 +/-19.01. A significant positive correlation of sexual harassment with depression, anxiety, stress and combined effect of them (DASS) was found. Multiple regression analysis showed sexual harassment as significant predictor of depression (beta= 0.47, p < .001), anxiety (beta= 0.43, p < .001) and stress (beta= 0.45, p < .001) in nurses. CONCLUSION: Sexual harassment was found to be a predictor of negative mental health in the form of depression, anxiety and stress in nurses of public hospitals. PMID- 26374366 TI - Temozolomide for Treating Malignant Melanoma. AB - Melanoma is one of the most malignant forms of skin cancer; with a rapidly increasing prevalence. Early-stage melanoma is curable, but advanced metastatic melanoma is almost always fatal, and patients with such advanced disease have short median survival. Surgery and radiotherapy play a limited role in the treatment of metastatic melanoma. Rather, chemotherapy remains the mainstay of treatment, although other approaches, including biotherapy and gene therapy, have been attempted. The authors hereby, evaluated the use of temozolomide (TMZ) for treating metastatic melanoma compared to dacarbazine (DTIC), the effectiveness of TMZ for treating brain metastases, as well as TMZ resistance and how the efficacy of TMZ in malignant melanoma can be increased. Two chemotherapeutic regimens are commonly used for palliative treatment of malignant melanoma: intravenous administration of DTIC and oral administration of the alkylating agent temozolomide (TMZ). Compared to DTIC, TMZ is very well tolerated and has an advantage in terms of improving the quality of life of patients with metastatic melanoma. While the prognosis is currently unpromising, chemotherapy plays a palliative role for patients with metastatic melanoma. The toxicity of treatment regimens based on DTIC and TMZ do not differ significantly, although TMZ is costlier. These findings provide a reference for future researchers via a comprehensive analysis of the relevant literature. PMID- 26374367 TI - beta-Blocker Therapy for Patients with Hypertension. PMID- 26374368 TI - Situs ambiguousin an Adult with Congenital Cardiovascular and Musculoskeletal Defect. AB - Situs ambiguous(SA) is an abnormality in which the thoracic and abdominal organs are not clearly lateralized. Situs ambiguous with polysplenia is usually associated with complex cardiovascular abnormalities and rarely found among adults due to high mortality at younger age. We are reporting a rare cluster of Situs ambiguous with polysplenia (left isomerism) in an adult with congenital hand deformity and cardiovascular pathology, who presented with ascites and decompensated congestive cardiac failure due to dilated cardiomyopathy. He had congenital agenesis of left hand fingers and hypoplastic left thumb. Electrocardiogram and imaging findings were consistent with dextrocardia, Situs inversus and features of left isomerism. Echocardiography showed severe biventricular failure with prominent coronary sinus. Such a combination of musculoskeletal and cardiovascular pathologies was not reported in the literature. His coronary arteries were normal. He had successful single chamber Implantable Cadioverter Defibrillator (ICD) insertion. PMID- 26374369 TI - Optic Nerve Metastasis from Squamous Cell Carcinoma of the Uterine Cervix. AB - Metastatic involvement of the optic nerve or its sheath is very rare (1.3 - 3%). The most common malignancies reported to metastasize to the optic nerve or its sheath are breast, lung, kidney, bladder, gastric and colorectal cancers. Carcinoma of uterine cervix metastatic to optic nerve and optic nerve sheath is extremely rare and is associated with grave prognosis due to underlying high tumor burden. Here in, we report a 61-year Saudi woman who was treated with concurrent chemoradiation for squamous cell carcinoma of cervix FIGO IVA 6 months back. She presented with pain and progressive visual loss in the right eye. Magnetic resonance imaging showed enhanced solid mass of the intraorbital optic nerve consistent with optic nerve sheath meningioma. Immunostaining (CK5/6, CAM 5.2, p63 and p16) confirmed the diagnosis of metastatic squamous cell carcinoma of uterine cervix. PMID- 26374370 TI - LASER Treatment of Laryngeal Papillomatosis in a Young Child: Anaesthetic and Surgical Management. AB - The authors report the case of a 4-year boy who required anaesthetic and surgical care during LASER excision of laryngeal papillomatosis. He presented with hoarseness and stridor and underwent emergency tracheostomy after confirmation of laryngeal papillomas on CT scan. He required LASER treatment under general anaesthesia with a requirement of paediatric LASER-safe endotracheal tube but unfortunately, this was not available in the country. Balanced anaesthesia technique using inhalational anaesthetic, muscle relaxant and narcotic is used with modifications. After three successful surgical sessions, the airway became patent and tracheostomy was de-cannulated. The perioperative issues surrounding this process are discussed including anaesthetic induction in the patient with a compromised airway, maintenance anaesthetic techniques, methods used for ventilation during LASER surgery of the upper airway, surgical implications and hazards of LASER to the operating room personnel. PMID- 26374371 TI - The Role of Intraarticular Platelet Rich Plasma (PRP) Injection in Patients with Internal Knee Derangements. AB - Platelet Rich Plasma (PRP) is an emerging biotechnology which uses patient's own blood components to create healing effect to their own injured tissues. This study was carried out to evaluate the clinical effects, adverse reactions and patient satisfaction after intraarticular injection of platelet rich plasma in a small group of patients with internal derangements of knee at Combined Military Hospital, Panoaqil, Pakistan. In this single center, open study, 10 patients with internal derangements of knee fulfilling the inclusion criteria received two doses of 3 ml of platelet rich plasma as intraarticular knee injection at two weeks interval. All patients were evaluated at 0, 4 and 12 weeks after treatment using IKDC, TEGNER, KOOS and VAS. Adverse events and patient's satisfaction was recorded. There was significant improvement in all scores. Intraarticular PRP injection is safe and effective method in the conservative treatment of internal knee derangements. PMID- 26374372 TI - Clinical Evaluation of Proximal Contact Points in Fixed Prostheses. AB - This cross-sectional study clinically assesses the tightness of proximal contact points of fixed dental prosthesis with natural teeth. Sixty nine (69) patients visiting the Department of Prosthodontics, Armed Forces Institute of Dentists (AFID), Rawalpindi, were included. The crowns, as a single unit or terminal abutment of bridge, prepared and fabricated at the same institute were included. A total of 142 Proximal Contact Points (PCPs) were assessed with the dental floss and categorized as acceptable, loose and tight. Among these, 83 (58.4%) were acceptable, 41 (28.8%) loose and 18 (12.6%) were tight. Out of 142 PCPs, 104 (73.2%) were Porcelain Fused to Metal (PFM) and 38 (26.7%), all metal. Out of 104 PFM crown/FPD PCPs 59 (56.7%) were acceptable, 32 (30.7%) were loose and 13 (12.5%) tight. Out of 38 all metal crown/FPD PCPs 24 (63%) acceptable, 9 (23%) were loose and 5 (13%) were tight. PCPs must be checked for acceptability before cementation. The PCPs of adjacent natural dentition in same patient may serve as guide for assessment. PMID- 26374373 TI - Small Defect - Big Anaesthetic Concern. PMID- 26374374 TI - Painless Aortic Dissection with Hypotension. PMID- 26374375 TI - Track Extubation in Pediatric Congenital Heart Disease Open Heart Surgical Patients in Pakistan. PMID- 26374376 TI - Cutaneous Larva Migrans on Upper Abdomen: An Unusual Site. PMID- 26374377 TI - Emerging cool white light emission from Dy(3+) doped single phase alkaline earth niobate phosphors for indoor lighting applications. AB - Single-phase cool white-light emitting BaNb2O6:Dy(3+) phosphors have been synthesized via a conventional solid-state reaction method and characterized using X-ray diffraction (XRD), scanning electron microscopy (SEM) observations and spectrofluorophotometric measurements. XRD and Rietveld structural refinement studies confirm that all the samples exhibit pure orthorhombic structure [space group -C2221(20)]. SEM observations reveal the dense particle packaging with irregular morphology in a micron range. The as-prepared phosphors exhibit blue (482 nm) and yellow (574 nm) emissions under 349, 364, 386 and 399 nm excitations corresponding to (4)F9/2->(6)HJ (J = 15/2, 13/2) transitions of Dy(3+) ions. The energy transfer mechanism between Dy(3+) ions has been studied in detail and the luminescence decay lifetime for the (4)F9/2 level was found to be around 146.07 MUs for the optimized phosphor composition. The calculated Commission Internationale de L'Eclairage (CIE) chromaticity coordinates for the optimized phosphor are (x = 0.322, y = 0.339), which are close to the National Television Standard Committee (NTSC) (x = 0.310, y = 0.316) coordinates. The values of CIE chromaticity coordinates and correlated color temperature (CCT) of 5907 K endorse cool white-light emission from the phosphor. The study reveals that BaNb2O6:Dy(3+) phosphor could be a potential candidate for near ultra-violet (NUV) excited white-LED applications. PMID- 26374379 TI - Large orb-webs adapted to maximise total biomass not rare, large prey. AB - Spider orb-webs are the ultimate anti-ballistic devices, capable of dissipating the relatively massive kinetic energy of flying prey. Increased web size and prey stopping capacity have co-evolved in a number orb-web taxa, but the selective forces driving web size and performance increases are under debate. The rare, large prey hypothesis maintains that the energetic benefits of rare, very large prey are so much greater than the gains from smaller, more common prey that smaller prey are irrelevant for reproduction. Here, we integrate biophysical and ecological data and models to test a major prediction of the rare, large prey hypothesis, that selection should favour webs with increased stopping capacity and that large prey should comprise a significant proportion of prey stopped by a web. We find that larger webs indeed have a greater capacity to stop large prey. However, based on prey ecology, we also find that these large prey make up a tiny fraction of the total biomass (=energy) potentially captured. We conclude that large webs are adapted to stop more total biomass, and that the capacity to stop rare, but very large, prey is an incidental consequence of the longer radial silks that scale with web size. PMID- 26374380 TI - Sprint running research speeds up: A first look at the mechanics of elite acceleration. PMID- 26374381 TI - Digital breast tomosynthesis at screening assessment: are two views always necessary? AB - OBJECTIVE: The current recommendation from the UK National Health Service Breast Screening Programme is that digital breast tomosynthesis (DBT) can be used for further assessment of possible screen-detected soft-tissue abnormalities in place of spot compression views and when used should be performed in two projections. The aim of the study was to assess whether two-view DBT is necessary if the abnormality is seen only in one view on initial full-field digital mammography (FFDM). METHODS: 617 cases with possible masses, distortions and asymmetrical densities visualized only in one view on screening FFDM were included. All of these females underwent two-view DBT, clinical examination and ultrasound. The FFDM and DBT findings on each view were compared and correlated with the histological diagnosis. RESULTS: 586 of 617 cases had normal or benign findings on further assessment, and no additional information was obtained on the other DBT view. There were 31 confirmed cancers. In 26 cases (84%), the cancer was seen on the corresponding DBT view. No cancer was seen on the other DBT view alone. Five cancers (16%) were not seen on either view on DBT owing to technical reasons. No cancers would have been missed if only the corresponding DBT view was performed. CONCLUSION: Two-view DBT may not be necessary when used for further assessment of possible screen-detected soft-tissue abnormalities. Larger studies should be undertaken to investigate this further. ADVANCES IN KNOWLEDGE: One-view DBT may be adequate in assessing soft-tissue abnormalities seen only on one FFDM view. PMID- 26374382 TI - Proteomic analysis of the Simkania-containing vacuole: the central role of retrograde transport. AB - Simkania negevensis is an obligate intracellular bacterial pathogen that grows in amoeba or human cells within a membrane-bound vacuole forming endoplasmic reticulum (ER) contact sites. The membrane of this Simkania-containing vacuole (SnCV) is a critical host-pathogen interface whose origin and molecular interactions with cellular organelles remain poorly defined. We performed proteomic analysis of purified ER-SnCV-membranes using label free LC-MS(2) to define the pathogen-containing organelle composition. Of the 1,178 proteins of human and 302 proteins of Simkania origin identified by this strategy, 51 host cell proteins were enriched or depleted by infection and 57 proteins were associated with host endosomal transport pathways. Chemical inhibitors that selectively interfere with trafficking at the early endosome-to-trans-Golgi network (TGN) interface (retrograde transport) affected SnCV formation, morphology and lipid transport. Our data demonstrate that Simkania exploits early endosome-to-TGN transport for nutrient acquisition and growth. PMID- 26374383 TI - Infants understand deceptive intentions to implant false beliefs about identity: New evidence for early mentalistic reasoning. AB - Are infants capable of representing false beliefs, as the mentalistic account of early psychological reasoning suggests, or are they incapable of doing so, as the minimalist account suggests? The present research sought to shed light on this debate by testing the minimalist claim that a signature limit of early psychological reasoning is a specific inability to understand false beliefs about identity: because of their limited representational capabilities, infants should be unable to make sense of situations where an agent mistakes one object for another, visually identical object. To evaluate this claim, three experiments examined whether 17-month-olds could reason about the actions of a deceptive agent who sought to implant in another agent a false belief about the identity of an object. In each experiment, a thief attempted to secretly steal a desirable rattling toy during its owner's absence by substituting a less desirable silent toy. Infants realized that this substitution could be effective only if the silent toy was visually identical to the rattling toy (Experiment 1) and the owner did not routinely shake her toy when she returned (Experiment 2). When these conditions were met, infants expected the owner to be deceived and to mistake the silent toy for the rattling toy she had left behind (Experiment 3). Together, these results cast doubt on the minimalist claim that infants cannot represent false beliefs about identity. More generally, these results indicate that infants in the 2nd year of life can reason not only about the actions of agents who hold false beliefs, but also about the actions of agents who seek to implant false beliefs, thus providing new support for the mentalistic claim that an abstract capacity to reason about false beliefs emerges early in human development. PMID- 26374384 TI - Three-dimensional morphogenesis of MDCK cells induced by cellular contractile forces on a viscous substrate. AB - Substrate physical properties are essential for many physiological events such as embryonic development and 3D tissue formation. Physical properties of the extracellular matrix such as viscoelasticity and geometrical constraints are understood as factors that affect cell behaviour. In this study, we focused on the relationship between epithelial cell 3D morphogenesis and the substrate viscosity. We observed that Madin-Darby Canine Kidney (MDCK) cells formed 3D structures on a viscous substrate (Matrigel). The structures appear as a tulip hat. We then changed the substrate viscosity by genipin (GP) treatment. GP is a cross-linker of amino groups. Cells cultured on GP-treated-matrigel changed their 3D morphology in a substrate viscosity-dependent manner. Furthermore, to elucidate the spatial distribution of the cellular contractile force, localization of mono-phosphorylated and di-phosphorylated myosin regulatory light chain (P-MRLCs) was visualized by immunofluorescence. P-MRLCs localized along the periphery of epithelial sheets. Treatment with Y-27632, a Rho-kinase inhibitor, blocked the P-MRLCs localization at the edge of epithelial sheets and halted 3D morphogenesis. Our results indicate that the substrate viscosity, the substrate deformation, and the cellular contractile forces induced by P-MRLCs play crucial roles in 3D morphogenesis. PMID- 26374386 TI - Investigation of a 6-MSA Synthase Gene Cluster in Aspergillus aculeatus Reveals 6 MSA-derived Aculinic Acid, Aculins A-B and Epi-Aculin A. AB - Aspergillus aculeatus, a filamentous fungus belonging to the Aspergillus clade Nigri, is an industrial workhorse in enzyme production. Recently we reported a number of secondary metabolites from this fungus; however, its genetic potential for the production of secondary metabolites is vast. In this study we identified a 6-methylsalicylic acid (6-MSA) synthase from A. aculeatus, and verified its functionality by episomal expression in A. aculeatus and heterologous expression in A. nidulans. Feeding studies with fully (13) C-labeled 6-MSA revealed that 6 MSA is incorporated into aculinic acid, which further incorporates into three compounds that we name aculins A and B, and epi-aculin A, described here for the first time. Based on NMR data and bioinformatic studies we propose the structures of the compounds as well as a biosynthetic pathway leading to formation of aculins from 6-MSA. PMID- 26374387 TI - Postnatal environmental tobacco smoke exposure is associated with objective markers of atopy in preschool-aged children. PMID- 26374390 TI - CH Bond Activation of Methane by a Transient eta(2) Cyclopropene/Metallabicyclobutane Complex of Niobium. AB - This study challenges the problem of the activation of a CH bond of methane by soluble transition metal complexes. High pressure solution NMR, isotopic labeling studies, and kinetic analyses of the degenerate exchange of methane in the methyl complex [Tp(Me2)NbCH3(c-C3H5)(MeCCMe)] (1) are reported. Stoichiometric methane activation by the mesitylene complex [Tp(Me2)Nb(CH2-3,5-C6H3Me2)(c-C3H5) (MeCCMe)] (2) giving 1 is also realized. Evidence is provided that these reactions proceed via an intramolecular abstraction of a beta-H of the cyclopropyl group to form either methane or mesitylene from 1 or 2, respectively, yielding the transient unsaturated eta(2)-cyclopropene/metallabicyclobutane intermediate [Tp(Me2)Nb(eta(2)-c-C3H4) (MeCCMe)] A. This is followed by its mechanistic reverse 1,3-CH bond addition of methane yielding the product. PMID- 26374389 TI - Activation of a dormant replication origin is essential for Haloferax mediterranei lacking the primary origins. AB - The use of multiple origins for chromosome replication has been demonstrated in archaea. Similar to the dormant origins in eukaryotes, some potential origins in archaea appear to be inactive during genome replication. We have comprehensively explored the origin utilization in Haloferax mediterranei. Here we report three active chromosomal origins by genome-wide replication profiling, and demonstrate that when these three origins are deleted, a dormant origin becomes activated. Notably, this dormant origin cannot be further deleted when the other origins are already absent and vice versa. Interestingly, a potential origin that appears to stay dormant in its native host H. volcanii lacking the main active origins becomes activated and competent for replication of the entire chromosome when integrated into the chromosome of origin-deleted H. mediterranei. These results indicate that origin-dependent replication is strictly required for H. mediterranei and that dormant replication origins in archaea can be activated if needed. PMID- 26374391 TI - Increased susceptibility of skin from HERDA (Hereditary Equine Regional Dermal Asthenia)-affected horses to bacterial collagenase degradation: a potential contributing factor to the clinical signs of HERDA. AB - BACKGROUND: Hereditary equine regional dermal asthenia (HERDA) is a genetic disorder of collagen resulting in fragile, hyper-extensible skin and ulcerative lesions. The predominance of skin lesions have been shown to occur on the dorsum of HERDA-affected horses. While this has been postulated to be due to increased exposure to sunlight of these areas, the precise pathological mechanism which causes this to occur is unclear. HYPOTHESIS/OBJECTIVES: We hypothesized that an increase in collagenase activity, that has been associated with the exposure of dermal fibroblasts to sunlight, will significantly degrade the material properties of skin from HERDA-affected horses when compared to unaffected controls. ANIMALS: Six unaffected and seven HERDA-affected horses, all euthanized for other reasons. METHODS: Full-thickness skin samples from similar locations on each horse were collected and cut into uniform strips and their material properties (tensile modulus) determined by mechanical testing before (n = 12 samples/horse) or after (n = 12 samples/horse) incubation in bacterial collagenase at 37 degrees C for 6 h. The change in modulus following treatment was then compared between HERDA-affected and unaffected horses using a Student's t-test. RESULTS: The modulus of skin from HERDA-affected horses decreased significantly more than that from unaffected horses following collagenase treatment (54 +/- 7% versus 30 +/- 16%, P = 0.004). CONCLUSIONS AND CLINICAL IMPORTANCE: The significant decrease in the modulus of skin from HERDA-affected horses following collagenase exposure suggests that their altered collagen microarchitecture is more susceptible to enzymatic degradation and may explain the localization of skin lesions in HERDA-affected horses to those areas of the body most exposed to sunlight. These findings appear to support the previously reported benefits of sunlight restriction in HERDA-affected horses. PMID- 26374392 TI - Cinnamon intake reduces serum T3 level and modulates tissue-specific expression of thyroid hormone receptor and target genes in rats. AB - BACKGROUND: Cinnamon has several effects on energy metabolism. However, no data exist on the impact of cinnamon intake on thyroid hormone serum concentrations and action, since thyroid hormones (THs) play a major role in metabolism. RESULTS: Male rats were treated with cinnamon water extract (400 mg kg(-1) body weight, 25 days). Cinnamon supplementation resulted in a lower serum total T3 level accompanied by normal serum T4 and TSH levels. The cinnamon-treated rats did not exhibit significant differences in TSHbeta subunit, TRbeta or deiodinase type 2 mRNA expression in the pituitary. In the liver, cinnamon did not change the TRbeta protein expression or the deiodinase type 1 mRNA expression, suggesting that there were no changes in T3 signaling or metabolism in this organ. However, mitochondrial GPDH, a target gene for T3 in the liver, exhibited no changes in mRNA expression, although its activity level was reduced by cinnamon. In the cardiac ventricle, T3 action was markedly reduced by cinnamon, as demonstrated by the lower TRalpha mRNA and protein levels, reduced SERCA2a and RyR2 and increased phospholamban mRNA expression. CONCLUSION: This study has revealed that TH action is a novel target of cinnamon, demonstrating impairment of T3 signaling in the cardiac ventricles. (c) 2015 Society of Chemical Industry. PMID- 26374393 TI - Tailoring the Synergistic Bronsted-Lewis acidic effects in Heteropolyacid catalysts: Applied in Esterification and Transesterification Reactions. AB - In order to investigate the influences of Lewis metals on acidic properties and catalytic activities, a series of Keggin heteropolyacid (HPA) catalysts, HnPW11MO39 (M = Ti(IV), Cu(II), Al(III), Sn(IV), Fe(III), Cr(III), Zr(IV) and Zn(II); for Ti and Zr, the number of oxygen is 40), were prepared and applied in the esterification and transesterification reactions. Only those cations with moderate Lewis acidity had a higher impact. Ti Substituted HPA, H5PW11TiO40, posse lower acid content compared with Ti(x)H(3-4x)PW12O40 (Ti partial exchanged protons in saturated H3PW12O40), which demonstrated that the Lewis metal as an addenda atom (H5PW11TiO40) was less efficient than those as counter cations (Ti(x)H(3-4x)PW12O40). On the other hand, the highest conversion reached 92.2% in transesterification and 97.4% in esterification. Meanwhile, a good result was achieved by H5PW11TiO40 in which the total selectivity of DAG and TGA was 96.7%. In addition, calcination treatment to H5PW11TiO40 make it insoluble in water which resulted in a heterogeneous catalyst feasible for reuse. PMID- 26374395 TI - Current imaging follow-up of non-Hodgkin lymphoma exposes patients to significant radiation but does not detect asymptomatic relapses. AB - The standard approach to the follow-up of lymphoma includes computed tomography (CT) every 6-12 months for the first 2 years and, then, as clinically indicated. Recent evidence suggests that most relapses are detected clinically, outside scheduled CT which, on the other hand, increases risk of second malignancies and cost. In early-stage lymphomas, involved site CT instead of full body CT may be a reasonable alternative to reduce radiation dose. We analyzed whether regular CT surveillance detects asymptomatic relapses in a single-center Uruguayan early stage non-Hodgkin lymphoma (NHL) population. We evaluated utility of full body CT halfway and at the end-of-treatment evaluation and calculated the radiation exposure. In our study, CT surveillance added nothing to clinical follow-up. Moreover, 44% of our patients received a cumulative effective dose that doubles the risk of malignancies. Involved-site CT scan would be enough to monitor response during treatment in early stage NHL. PMID- 26374394 TI - Molecular memories in the regulation of seasonal flowering: from competence to cessation. AB - Plants commit to flowering based on endogenous and exogenous information that they can remember across mitotic cell divisions. Here, we review how signal perception and epigenetic memory converge at key integrator genes, and we show how variation in their regulatory circuits supports the diversity of plant lifestyles. PMID- 26374396 TI - Experience of automation failures in training: effects on trust, automation bias, complacency and performance. AB - This work examined the effects of operators' exposure to various types of automation failures in training. Forty-five participants were trained for 3.5 h on a simulated process control environment. During training, participants either experienced a fully reliable, automatic fault repair facility (i.e. faults detected and correctly diagnosed), a misdiagnosis-prone one (i.e. faults detected but not correctly diagnosed) or a miss-prone one (i.e. faults not detected). One week after training, participants were tested for 3 h, experiencing two types of automation failures (misdiagnosis, miss). The results showed that automation bias was very high when operators trained on miss-prone automation encountered a failure of the diagnostic system. Operator errors resulting from automation bias were much higher when automation misdiagnosed a fault than when it missed one. Differences in trust levels that were instilled by the different training experiences disappeared during the testing session. Practitioner Summary: The experience of automation failures during training has some consequences. A greater potential for operator errors may be expected when an automatic system failed to diagnose a fault than when it failed to detect one. PMID- 26374397 TI - Importance of ICD-10 coding directive change for acute gastroenteritis (unspecified) for rotavirus vaccine impact studies: illustration from a population-based cohort study from Ontario, Canada. AB - BACKGROUND: In Ontario, Canada, we conducted an evaluation of rotavirus (RV) vaccine on hospitalizations and Emergency Department (ED) visitations for acute gastroenteritis (AGE). In our original analysis, any one of the International Classification of Disease, Version 10 (ICD-10) codes was used for outcome ascertainment: RV-specific- (A08.0), viral- (A08.3, A08. 4, A08.5), and unspecified infectious- gastroenteritis (A09). Annual age-specific rates per 10,000 population were calculated. FINDINGS: The average monthly rate of AGE hospitalization for children under age two increased from 0.82 per 10,000 from January 2003 to March 2009, to 2.35 over the period of April 2009 to March 31, 2013. Similar trends were found for ED consultations and in other age groups. A rise in events corresponding to the A09 code was found when the outcome definition was disaggregated by ICD-10 code. Documentation obtained from the World Health Organization confirmed that a change in directive for the classification of unspecified gastroenteritis occurred with the release of ICD-10 in April 2009. AGE events previously classified under the code K52.9, are now classified under code A09.9. CONCLUSIONS: Based on change in the classification of unspecified gastroenteritis we modified our outcome definition to also include unspecified non-infectious-gastroenteritis (K52.9). We recommend other investigators consider using both A09.9 and K52.9 ICD-10 codes for outcome ascertainment in future rotavirus vaccine impact studies to ensure that all unspecified cases of AGE are captured, especially if the study period spans 2009. PMID- 26374398 TI - Inequity in costs of seeking sexual and reproductive health services in India and Kenya. AB - OBJECTIVE: This study aims to assess inequity in expenditure on sexual and reproductive health (SRH) services in India and Kenya. In addition, this analysis aims to measure the extent to which payments are catastrophic and to explore coping mechanisms used to finance health spending. METHODS: Data for this study were collected as a part of the situational analysis for the "Diagonal Interventions to Fast Forward Enhanced Reproductive Health" (DIFFER) project, a multi-country project with fieldwork sites in three African sites; Mombasa (Kenya), Durban (South Africa) and Tete (Mozambique), and Mysore in India. Information on access to SRH services, the direct costs of seeking care and a range of socio-economic variables were obtained through structured exit interviews with female SRH service users in Mysore (India) and Mombasa (Kenya) (n = 250). The costs of seeking care were analysed by household income quintile (as a measure of socio-economic status). The Kakwani index and quintile ratios are used as measures of inequitable spending. Catastrophic spending on SRH services was calculated using the threshold of 10% of total household income. RESULTS: The results showed that spending on SRH services was highly regressive in both sites, with lower income households spending a higher percentage of their income on seeking care, compared to households with a higher income. Spending on SRH as a percentage of household income ranged from 0.02 to 6.2% and 0.03-7.5% in India and Kenya, respectively. There was a statistically significant difference in the proportion of spending on SRH services across income quintiles in both settings. In India, the poorest households spent two times, and in Kenya ten times, more on seeking care than the least poor households. The most common coping mechanisms in India and Kenya were "receiving [money] from partner or household members" (69%) and "using own savings or regular income" (44%), respectively. CONCLUSION: Highly regressive spending on SRH services highlights the heavier burden borne by the poorest when seeking care in resource-constrained settings such as India and Kenya. The large proportion of service users, particularly in India, relying on money received from family members to finance care seeking suggests that access would be more difficult for those with weak social ties, small social networks or weak bargaining positions within the family - although this requires further study. PMID- 26374399 TI - Desire for hastened death: how do professionals in specialized palliative care react? AB - OBJECTIVE: Desires for hastened death (DHD; wish to hasten death is also in use) are prevalent in terminally ill patients. Studies show that health professionals (HP) are often underprepared when presented with DHD. HPs in specialized palliative care (SPC-HP) often encounter DHD. This study aimed to identify SPC-HP responses to DHD in daily practice and their corresponding functions. METHODS: Narrative interviews were conducted with 19 SPC-HPs at four German University Hospitals. Transcripts were analyzed using the documentary method. An inventory of established responses to DHD was compiled, and their corresponding functions in the context of the patient-SPC-HP interaction were reconstructed. RESULTS: Twelve response categories and six corresponding functions were identified. On the patient level, responses categorized as symptom control, exploring the reasons and generating perspective, reorientation, and hope were particularly used to ease the patient's burden. On the interaction level, creating a relationship was fundamental. On the SPC-HP level, various methods served the functions self-protection and showed professional expertise. CONCLUSIONS: Profound personal and professional development is necessary to respond to the inherent challenges presented by DHD. Establishing helpful relationships with patients is essential regardless of SPC-HP specialization. SPC-HPs should maximize their skills in establishing and maintaining relationships as well as strengthening their own resilience, possibly in specific training courses. PMID- 26374400 TI - Phylogenetic analysis reveals positive correlations between adaptations to diverse hosts in a group of pathogen-like herbivores. AB - A jack of all trades can be master of none-this intuitive idea underlies most theoretical models of host-use evolution in plant-feeding insects, yet empirical support for trade-offs in performance on distinct host plants is weak. Trade-offs may influence the long-term evolution of host use while being difficult to detect in extant populations, but host-use evolution may also be driven by adaptations for generalism. Here we used host-use data from insect collection records to parameterize a phylogenetic model of host-use evolution in armored scale insects, a large family of plant-feeding insects with a simple, pathogen-like life history. We found that a model incorporating positive correlations between evolutionary changes in host performance best fit the observed patterns of diaspidid presence and absence on nearly all focal host taxa, suggesting that adaptations to particular hosts also enhance performance on other hosts. In contrast to the widely invoked trade-off model, we advocate a "toolbox" model of host-use evolution in which armored scale insects accumulate a set of independent genetic tools, each of which is under selection for a single function but may be useful on multiple hosts. PMID- 26374401 TI - Sphingobacterium suaedae sp. nov., isolated from the rhizosphere soil of Suaeda corniculata. AB - A Gram-stain-negative, non-motile, non-spore-forming bacterium, designated T47T, was isolated from saline soil of the Suaeda corniculata rhizosphere, located on the bank of Wuliangsuhai Lake, Inner Mongolia, northern China. Strain T47T could grow at 10-40 degrees C (with 30 degrees C the optimal temperature), pH 6.0-8.0 (optimal pH 6.0) and in the presence of 0-6.0 % (w/v) NaCl [optimal 0-1.0 % (w/v)]. Phylogenetic analysis, based on 16S rRNA gene sequences, revealed that strain T47T formed a stable clade with Sphingobacterium composti 4M24T, Sphingobacterium bambusae IBFC2009T, Sphingobacterium paludis S37T and Sphingobacterium wenxiniae LQY-18T, with the 16S rRNA gene sequence similarities ranging from 91.9-95.4 %. Its major cellular fatty acids contained iso-C15 : 0 (39.9 %), summed feature 3 (iso-C15 : 0 2-OH and/or C16 : 1omega7c, 23.0 %), C16 : 0 (12.8 %) and iso-C17 : 0 3-OH (9.9 %). MK7 was the major menaquinone. The G+C content of the genomic DNA was 45.5 mol%. Based on the phenotypic, phylogenetic and genotypic characteristics, strain T47T represents a novel species within the genus Sphingobacterium, for which the name Sphingobacterium suaedae sp. nov. is proposed. The type strain is T47T ( = CGMCC 1.15277T = KCTC 42662T). PMID- 26374402 TI - Human brucellosis: sero-prevalence and associated risk factors in agro-pastoral communities of Kiboga District, Central Uganda. AB - BACKGROUND: Brucellosis remains a neglected zoonotic disease among agro-pastoral communities where unprocessed milk and milk products are consumed. A cross sectional study was carried out in Kiboga district to determine the seroprevalence and risk factors associated with human brucellosis in communities where livestock rearing in a common practice. METHODS: A total of 235 participants were involved in the study. Blood samples from the participants were collected and screened for Brucella using Serum Agglutination Test and Rose Bengal Plate Test. A questionnaire was used to collect data on socio-demographic characteristics and human brucellosis related risk factors. RESULTS: Human Brucella seroprevalence was at 17.0 % (n = 235). The prevalence was highest among males (20.5 %, n = 78) and the elderly - above 60 years (22.2 %, n = 18). Residence in rural areas (OR 3.16, 95 % CI: 1.16-8.56), consuming locally processed milk products (OR 2.54, 95 % CI: 1.12-5.78) and being single (OR 2.44, 95 % CI: 1.05-5.68), were associated with increased risk of brucellosis. DISCUSSION: Human brucellosis seroprevalence was high at 17 %, this was parallel with animal brucellosis prevalence that has been reported to range from 10.2 % to 25.7 % in cattle in the region. The participants were from communities known to habitually consume raw milk and milk products, know to process milk products using bare hands which are major risk factors for brucellosis in humans. This also explains why consumption of unpasteurized milk products was associated with the occurrence of brucellosis in study area. This strengthened the argument that humans get infected through consumption of contaminated animal products as reported in other earlier studies. Males and elderly being more affected because of traditional roles of these groups they play in livestock care and management. The single were also to be more associated to brucellosis, due to the fact that this group consume milk and milk products more as it is readily available in the informal markets as highly nutritious fast foods in this community as also observed in USA. CONCLUSIONS: Brucellosis is highly prevalent in Kiboga district, and therefore, an important public health problem. The transmission risk was aggravated by consumption of unpasteurized milk products, residing in rural settings and being single. There is a need to initiate screening, treat infected humans early, and educate the public about risk factors and appropriate preventive measures of brucellosis. PMID- 26374403 TI - Transcriptional profiling of differentially vulnerable motor neurons at pre symptomatic stage in the Smn (2b/-) mouse model of spinal muscular atrophy. AB - INTRODUCTION: The term motor neuron disease encompasses a spectrum of disorders in which motor neurons are the lost. Importantly, while some motor neurons are lost early in disease and others remain intact at disease end-stage. This creates a valuable experimental paradigm to investigate the factors that regulate motor neuron vulnerability. Spinal muscular atrophy is a childhood motor neuron disease caused by mutations or deletions in the SMN1 gene. Here, we have performed transcriptional analysis on differentially vulnerable motor neurons from an intermediate mouse model of Spinal muscular atrophy at a presymptomatic time point. RESULTS: We have characterised two differentially vulnerable populations, differing in the level neuromuscular junction loss. Transcriptional analysis on motor neuron cell bodies revealed that reduced Smn levels correlate with a reduction of transcripts associated with the ribosome, rRNA binding, ubiquitination and oxidative phosphorylation. Furthermore, P53 pathway activation precedes neuromuscular junction loss, suggesting that denervation may be a consequence, rather than a cause of motor neuron death in Spinal muscular atrophy. Finally, increased vulnerability correlates with a decrease in the positive regulation of DNA repair. CONCLUSIONS: This study identifies pathways related to the function of Smn and associated with differential motor unit vulnerability, thus presenting a number of exciting targets for future therapeutic development. PMID- 26374404 TI - Effectiveness of tocilizumab with and without synthetic disease-modifying antirheumatic drugs in rheumatoid arthritis: results from a European collaborative study. AB - OBJECTIVES: To examine the effectiveness of tocilizumab (TCZ) with and without synthetic disease-modifying antirheumatic drugs (sDMARDs) in a large observational study. METHODS: Patients with rheumatoid arthritis treated with TCZ who had a baseline visit and information on concomitant sDMARDs were included. According to baseline data, patients were considered as taking TCZ as monotherapy or combination with sDMARDs. Main study outcomes were the change of Clinical Disease Activity Index (CDAI) and TCZ retention. The prescription of TCZ as monotherapy was analysed using logistic regression. CDAI change was analysed with a mixed-effects model for longitudinal data. TCZ retention was analysed with a stratified extended Cox model. RESULTS: Multiple-adjusted analysis suggests that prescription of TCZ as monotherapy varied according to age, corticosteroid use, country of the registry and year of treatment initiation. The change of disease activity assessed by CDAI as well as the likelihood to be in remission were not significantly different whether TCZ was used as monotherapy or in combination with sDMARDs in a covariate-adjusted analysis. Estimates for unadjusted median TCZ retention were 2.3 years (95% CI 1.8 to 2.7) for monotherapy and 3.7 years (lower 95% CI limit 3.1, upper limit not estimable) for combination therapies. In a covariate-adjusted analysis, TCZ retention was also reduced when used as monotherapy, with an increasing difference between mono and combination therapy over time after 1.5 years (p=0.002). CONCLUSIONS: TCZ with or without concomitant sDMARDs resulted in comparable clinical response as assessed by CDAI change, but TCZ retention was shorter under monotherapy of TCZ. PMID- 26374405 TI - Five-year experience with infliximab: Follow up of the product familiarisation program. AB - This 5-year retrospective analysis is of 22 patients who participated in the product familiarisation program (PFP) at St Vincent's Hospital Melbourne, prior to the listing of infliximab on the Pharmaceutical Benefit Scheme. Criteria for inclusion were being an adult with chronic plaque psoriasis, having a psoriasis area and severity index (PASI) score of at least 15 with an inadequate response or intolerance to three of the following: phototherapy, acitretin, cyclosporin and methotrexate. Participants were infused with infliximab 5 mg/kg on the standard induction (weeks 0, 2 and 6) and maintenance (8-weekly) protocols. At each visit PASI and dermatology life quality index (DLQI) scores were recorded. Success was determined as the proportion of patients achieving at least a 75% improvement in the PASI score from baseline (PASI 75). At 60 months after commencement of therapy, 31% of patients remained on infliximab. Those who did retained PASI 75 with a DLQI of 0 or 1. Of those who ceased infliximab, nine did so due to loss of efficacy, three for personal reasons, two for serious adverse events and one was lost to follow up. Adverse events included non-melanoma skin cancers, infections and abnormal liver enzymes. Infliximab in the Australian context has proven to be a highly effective treatment of chronic plaque psoriasis, and patients who remained on the drug derived a high level of satisfaction, assessed both subjectively (DLQI) and objectively (PASI 75). The variable response indicates that psoriasis is a heterogeneous disease and investigation into potential patient selection for treatment in the future is warranted. PMID- 26374406 TI - Differential mRNA expression profiling in ovarian endometriotic tissue with versus without leuprolide acetate treatment. AB - AIM: Leuprolide acetate, an analog of gonadotropin-releasing hormone (GnRH), regresses endometriotic tissue and reduces pain, resulting in clinical improvement upon treatment. The molecular mechanisms involved in the regression of endometriotic tissue, however, remain to be elucidated. In this study, we performed genome-wide gene expression profiling of clinical specimens of ovarian endometrioma to obtain insight into the effects of leuprolide acetate treatment. METHODS: We obtained clinical samples from nine normal eutopic endometrium tissues, eight ovarian endometriotic tissues, and 12 leuprolide acetate-treated endometriotic tissues. We compared the gene expression profiles of the three groups using Affymetrix GeneChip Human genome arrays and bioinformatic analysis, including molecular concept analysis. RESULTS: Leuprolide acetate-treated endometriotic tissue showed downregulated genes associated with the biological functions of steroid hormone regulation, cell proliferation, inflammation, and intracellular signaling. These genes included PTGDS, GRP, APLP2, PLTP, and FGFRL1. In contrast, genes upregulated by leuprolide acetate treatment were associated with cell growth inhibition and apoptosis. These genes included CARD11 and USP18. CONCLUSIONS: These preliminary results based on GeneChip analysis suggest that leuprolide acetate treatment induces a modulation of gene expression that allows for cooperative alterations in disease state. This study gives new insight into the effects of leuprolide acetate treatment. Further investigations with quantitative reverse transcription-polymerase chain reaction and immunohistochemistry are needed to validate this study and to explore new therapeutic targets and biomarkers of endometriosis. PMID- 26374407 TI - Preoperative Metyrosine Improves Cardiovascular Outcomes for Patients Undergoing Surgery for Pheochromocytoma and Paraganglioma. AB - BACKGROUND: The goal of preoperative pharmacotherapy for pheochromocytoma (PCC) and paraganglioma (PGL) resection is to minimize intraoperative hemodynamic instability and perioperative cardiovascular complications, but no standard preoperative regimen exists. Historically, treatment used metyrosine and phenoxybenzamine (MP). The recent metyrosine shortage required that phenoxybenzamine alone (PA) be used for treatment. The authors examined their experience to determine the impact of preoperative metyrosine treatment on patient outcomes. METHODS: A retrospective cohort study investigated patients who underwent initial PCC/PGL resection (2000-2014). The primary outcome was intraoperative hemodynamics, measured by heart rate (HR) and systolic blood pressure (SBP). The secondary outcomes included perioperative complications and cardiovascular-specific complications (CVC). Univariate analysis was performed, and adjusted risk differences were estimated after confounding was taken into account. RESULTS: Of 174 patients, 142 (81.6 %) were in the MP group. The MP and PA patients had comparable intraoperative use of antihypertensives (83.9 vs 78.1 %; p = 0.443), vasopressors (74.6 vs 87.5 %; p = 0.120), and fluid resuscitation (mean, 24.4 vs 24.8 ml/min; p = 0.761). Although the perioperative complication rate did not differ significantly between the MP and PA groups (respectively 23.4 vs 34.4 %; p = 0.198), the PA patients had a 15.8 % higher rate of CVC even after controlling for confounders (p = 0.034). Compared with the MP patients, the PA patients had significantly more hemodynamic instability intraoperatively, with a greater range in HR (7.4 bpm; p = 0.034) and SBP (14.8 mmHg; p = 0.020). CONCLUSIONS: In this study, preoperative metyrosine improved intraoperative hemodynamic stability and decreased CVC rates in patients undergoing PCC/PGLresection. These data suggest that the addition of preoperative metyrosine may improve operative outcomes. PMID- 26374408 TI - The effects of erythropoietin, dextran and saline on brain edema and lipid peroxidation in experimental head trauma. AB - BACKGROUND: The aim of this study was to investigate the protective effects of erythropoietin, dextran/saline and erythropoietin in combination with dextran/saline on brain edema and lipid peroxidation following traumatic brain injury in rats. METHODS: In the study, 40 male 3-month-old albino Wistar rats, weighing 250-340 g, were divided into four groups, each consisting of ten rats. Traumatic brain injury was induced in all rats by the weight-drop method, and erythropoietin (5,000 U/kg) and/or dextran and saline (8 ml/kg) solutions were injected intraperitoneally ten minutes after trauma. Control animals received an equal volume of serum physiologic. All rats were sacrificed 24 hours later. Glutathione peroxidase activity and malondialdehyde levels were measured in the left hemisphere, and edema was quantitated by the wet-dry method. RESULTS: Brain edema and the levels of malondialdehyde, the last product of lipid peroxidation in tissues, were decreased variably, and the activity of glutathione peroxidase, an antioxidant enzyme, was increased in others compared with the control group. CONCLUSION: In this study, it was concluded that the brain edema that developed in rats on which head trauma was induced and the secondary brain damage caused by oxidative stress could be deceased using a combination of erythropoietin, dextran, and saline. PMID- 26374409 TI - Detection of the MicroRNA expression profile in skeletal muscles of burn trauma at the early stage in rats. AB - BACKGROUND: Severe burn injuries are associated with a persistent hypermetabolic response, which causes long-term loss of muscle mass that results in a clinical negative balance of nitrogen and muscle wasting. MicroRNAs (miRNAs) play a critical role in post-transcriptional regulation of gene expression, which negatively regulates gene expression by promoting degradation of target mRNAs or inhibiting their translation. However, the mechanisms of skeletal muscle wasting after severe burn involved in miRNAs still remain unclear. METHODS: In this study, the alterations of miRNAs expression profile in skeletal muscles of thermal rats were detected at an early stage by microarray. All data were presented as mean+/-SD. Statistical analysis was determined by independent Student's t-test and one-way ANOVA. The significance was all set at p<0.05, and fold change cut-off was 2.0 for microarray. Significant differentially expressed miRNAs were identified through Volcano Plot filtering. Hierarchical clustering was performed using MEV software (v4.6, TIGR). RESULTS: Thousands of miRNAs could be examined in normal and injured tissues, but only 69 of these were significantly upregulated or down-regulated, which could be used to discriminate skeletal muscles of thermal rats from matched tissues. CONCLUSION: The deregulated miRNAs probably play a potential role in the pathogenesis of skeletal muscle wasting in burn trauma. PMID- 26374410 TI - Evaluation of gunshot wounds in the emergency department. AB - BACKGROUND: This study aimed to evaluate injury patterns of patients admitted to the emergency department with gunshot wounds, results of imaging studies, treatment modalities, outcomes, mortality ratios, and complications. METHODS: A retrospective descriptive study was carried out including a total number of one hundred and forty-two patients admitted to Hacettepe University Emergency Department with gunshot injuries between January 1, 1999 and December 31, 2013. The Glasgow Coma Scale (GCS), Revised Trauma Score (RTS), Injury Severity Score (ISS), and the Trauma and Injury Severity Score (TRISS) probability of survival for penetrating trauma were calculated for all patients. RESULTS: Among the one hundred and forty-two patients in the study, one hundred and twenty-eight (90.1%) were male. Mean age was 36 years. On admission, the average GCS score was 13, mean RTS was 6.64, median ISS was 5 and median TRISS probability for survival was 99.4% for penetrating trauma. Fluid was detected in three (13%) patients in FAST, whereas intra-abdominal solid organ injury and bowel injury were detected in 11 (58%) patients in abdominal CT. The pneumothorax, hemothorax and lung injuries were detected in 10 (40%) patients, whereas hemothorax was detected only in one patient with thoracic injury by chest X-ray. Twenty four (16.9%) patients died; eighteen patients (75%) had isolated severe intracranial injuries, two (8.3%) had thoracic injuries with head and neck injuries, and four (16.7%) patients had intra-abdominal organ injuries (one with concomitant head injury). Ten patients were brought to the ED in cardiopulmonary arrest. In dead patients, GCS, RTS and TRISS were significantly lower, and ISS were significantly higher than in surviving patients. Twenty three (95.8%) patients were in critical injury level (ISS 25-75, actually ISS >50) in the exitus group. CONCLUSION: Mortality rates in gunshot wound patients with cranial injuries are very high. Spontaneous return is not seen in patients brought to the ED in arrest state. Bullets can cause internal organ injuries which can be greater than expected. In thoracoabdominal gunshot wound injuries, conventional X-ray and bedside FAST can be ineffective in detecting the whole extent of intrathoracic and intra-abdominal injuries. Thus, thoracic and abdominal CT should be planned early for hemodynamically stable patients in order to eliminate causes of fatality and make a timely and correct diagnosis. ISS, RTS and GCS are useful in predicting prognosis and mortality. Especially in patients with ISS scores >50, the mortality rate can be as high as 96%. PMID- 26374411 TI - [The effect of clinical, laboratory and radiologic results on treatment decision and surgical results in patients admitted to the emergency department with blunt abdominal trauma due to traffic accident]. AB - BACKGROUND: The purpose of this study was to evaluate the effect of clinical, laboratory and radiological results on treatment decision and surgical results in patients with blunt abdominal trauma, who were admitted to the emergency department due to traffic accident. METHODS: Two hundred and twenty-two patients with blunt abdominal trauma were included into this retrospective study. Pearson chi square, Mann-Whitney U test and logistic regression methods were used for statistical analysis. RESULTS: All patients were analyzed by complete blood count and biochemistry and abdominal sonography. Eighty-two patients were also evaluated by CT. Twenty-three patients underwent surgery. Positive findings on physical examination, sonography and CT, increased white blood cell count and liver function tests, decreased hemoglobin were associated with the need for surgery. DISCUSSION: For the surgical evaluation of patients with blunt abdominal trauma, a reliable physical examination is not possible when the patients have concomitant injuries causing disturbing pain, or when the patients are unconscious. Laboratory tests should be interpreted with the clinical and radiologic analysis. Radiologic procedures play an important role in the management of patients with blunt abdominal trauma, especially for intubated patients. PMID- 26374412 TI - Evaluation of posttraumatic recurrent bacterial meningitis in adults. AB - BACKGROUND: Acute bacterial meningitis may develop as a complication after head trauma. The aim of this study was to present the demographic, clinical, microbiological and radiological characteristics of adult patients who presented with recurrent bacterial meningitis attacks after trauma. METHODS: Using a retrospective approach, the medical records of patients with acute recurrent bacterial meningitis (RBM) were reviewed, and those who had a history of trauma were included into the study. RBM was diagnosed based on clinical, bacteriologic and laboratory results. Demographic characteristics, clinical course, laboratory test results including cerebrospinal fluid analysis (CSF), radiological images, and the applied treatments were evaluated. RESULTS: A total of two hundred and twelve patients with acute bacterial meningitis were included into the study. RBM was diagnosed in twenty-five patients (11.8%), and in 18 of these patients (8.5%), the attacks had occurred subsequent to a trauma. In the CSF cultures of four patients, S. pneumoniae growth was observed. CT cisternography indicated CSF leaks in eleven patients. Moreover, bone fractures were observed in the CT images of ten patients. Ceftriaxone therapy was prescribed to 83% of the patients. Eight patients had a history of a fall in childhood, and five were involved in traffic accidents before acute bacterial meningitis. Four of the patients developed epilepsy and one developed deafness as sequelae. CONCLUSION: Since RBM attacks are frequently observed following trauma, in patients with a history of trauma who present with meningitis, the risk of recurrence should be considered. PMID- 26374413 TI - Choice of incision in penetrating cardiac injuries: Which one must we prefer: Thoracotomy or sternotomy? AB - BACKGROUND: Penetrating cardiac injuries are high-risk, high-mortality injuries considering the outcomes. Therefore, it is important to choose the appropriate incision. In general clinical settings, thoracotomy and median sternotomy are choices of incisions to explore the injury. In this study, the results of median sternotomy and thoracotomy in penetrating cardiac injuries were compared. METHODS: Between January 2003 and December 2013, forty patients, who underwent either thoracotomy or median sternotomy for penetrating cardiac injury, were retrospectively analyzed, and the collected data were compared. Twenty-six patients underwent thoracotomy (Group 1), and fourteen patients underwent median sternotomy (Group 2). RESULTS: There was no statistically significant gender difference between the groups. However, the mean age in Group 2 was found to be significantly higher than the one in Group 1 (p<0.05). CONCLUSION: There were no significant survival differences between the groups in the long term. Incision choice should be determined considering the site of injury and whether there is an accompanying pulmonary injury or not. On the other hand, thoracotomy has some draw backs compared to median sternotomy. PMID- 26374414 TI - Cerebrovascular complications of transorbital penetrating intracranial injuries. AB - BACKGROUND: Cerebrovascular trauma secondary to transorbital intracranial penetrating injury (TIPVI) is rare. Relatively benign initial presentation may mask the underlying life-threatening vascular injury in transorbital intracranial penetrations. The aim of this study was to evaluate clinical features and endovascular treatment of TIPVI. METHODS: Six patients with angiographic documentation of TIPVI in subacute/chronic phase were reviewed retrospectively. Five were treated endovascularly; however endovascular treatment was aborted in one and conservative management was pursued. RESULTS: Except for one case presenting with vision loss and mild stroke, no significant neurologic deficit was present. Vascular lesions included two cases of carotid-cavernous fistulas, three traumatic aneurysms of cavernous carotid, anterior and middle cerebral arteries and a unique case of coalescing cavernous aneurysms following a through and-through injury in which the aneurysms united within the thrombosed cavernous sinus on follow up. Fistulas were treated with covered stents, aneurysms with parent artery occlusion or flow diverters. All patients had uneventful recoveries. CONCLUSION: TIPVI may present in a delayed fashion after a seemingly benign presentation. A high index of suspicion is critical to rule out TIPVI with vascular imaging. Transcatheter angiographic techniques allow for both diagnosis and treatment of TIPVI with favorable results. PMID- 26374415 TI - Results of surgical treatment in metacarpal shaft fractures using low profile mini plates. AB - BACKGROUND: Metacarpal fractures are among the most common fractures of the hand. They may lead to loss of function if treated improperly. These injuries can be treated conservatively. However, if significant shortening, rotational deformity and angulation occur, surgical treatment is required. In this article, results of metacarpal fractures treated with open reduction and internal fixation with mini plates were presented. METHODS: We retrospectively reviewed the clinical and radiologic records of twenty-nine consecutive patients with 37 metacarpal fractures treated by open reduction and internal fixation with low profile mini plate fixation between 2006 and 2013. Surgical treatment with dorsal approach was planned for cases with unacceptable shortening, rotational deformity, and angulation. Early active motion was begun in all cases postoperatively. Patients were permitted to use their hands in daily activities four weeks after surgery. For objective assessment, total range of joint motion was measured. Rotational deformity of the fingers was assessed. Grip strength and quick DASH scores were compared with the uninjured side. Metacarpal shortening was evaluated radiologically, and angulation was measured. RESULTS: Mean age was 35.1 years (19 61 years) and mean follow-up period was 32 months (6-39 months). While mean operation time was 8.48 days (2-23 days), mean shortening was 7.58 (2-30) mm. In cases with radiologically documented union, mean angulation in the posteroanterior plane was 8.13 (0-42) degrees preoperatively and 3.55 (0-28) degrees postoperatively. In lateral X-rays, mean angulation was 8.22 (0-39) degrees preoperatively and 3.66 (0-28) degrees postoperatively. Mean quick DASH score was 3.6 (0-11.4). Mean grip strength measurements by Jamar hand dynamometer were 41.05 (+/-8.3) kg for fractured hands, 44.7 (+/-9) kg for normal hands. No significant relationship was found between normal hand and fracture hand by Mann Whitney U test. CONCLUSION: As in general fracture treatment principles, goals in metacarpal fracture treatment are obtaining an anatomical and stable reduction, fracture union and beginning early movement to avoid loss of function. Open reduction and low profile titanium plate application in metacarpal fractures is the choice of treatment in suitable cases as it meets the above mentioned treatment principles. PMID- 26374416 TI - Endovascular treatment for acute traumatic thoracic aortic transection. AB - BACKGROUND: This study aimed to present our experience in patients with acute traumatic thoracic aortic transection treated by endovascular stent-graft. METHODS: From October 2011 to October 2014, eleven patients were brought to our hospitals after suffering motor vehicle accident or fall from height. Computed tomography revealed acute traumatic transection of the thoracic aorta at the aortic isthmus just distal to the left subclavian artery in nine patients, at the middle or distal thoracic aorta in two, and both aortic isthmus and middle thoracic aorta in one. Endovascular technique was preferred as the treatment modality. All patients, except one, were treated within twelve hours of diagnosis. RESULTS: Deployment of stent-grafts was successful in all cases. The stent-grafts were oversized between 10% and 20%. The origin of left subclavian artery was covered with stent-graft in six patients to achieve adequate proximal landing zone. In two of them, carotico-subclavian bypass and periscope graft placement were applied to maintain subclavian artery blood flow. There were no procedure related deaths, paraplegia or ischemic complications. A patient with cardiac arrest, on whom cardiopulmonary resuscitation and transient aortic balloon occlusion within the aorta were applied in the angiography suit died at the postoperative twelve hours. Mean hospital stay after procedures was 14.8 days (range, 4-60 days). Mean follow-up time of ten patients was 16.6 months (range, 1 36 months). CONCLUSION: Our study supports that thoracic endovascular aortic stenting for acute transection is promising in terms of short- and mid-term results similar to other studies in the literature. PMID- 26374417 TI - Outcomes and demostration of cranial firearm injuries: A multicenter retrospective study. AB - BACKGROUND: Cranial firearm injuries (CFAI) are associated with significant morbidity and mortality.This study was aimed to determine the factors affecting mortality of CFAI cases managed in our institution by a retrospective analysis of CT scans and clinical data. METHODS: This multicenter retrospective study examined two hundred and nineteen patients presenting to neurosurgery clinics after CFAI between January 2012 and November 2014. Age, sex, Glasgow Coma Score (GCS), CT findings, and mortality and morbidity rates of the patients were analyzed to determine the factors affecting mortality. RESULTS: Mean age of the study population was 24.19+/-12.25 years, 85.8% of them were male. The most common CT findings were fracture (100%), intracranial hemorrhage (61.2%), and an intracranially located foreign body (44.3%). A cranial operation was performed in 64.8% of the victims. Mean GCS on admission was 8+/-3.9, which increased in survivors (p<0.05). CONCLUSION: CFAIs are associated with increased mortality and morbidity. We determined that many factors affected morbidity and mortality rates, and patient age, presence of intracranial hemorrhage, GCS, and treatment protocols were significantly associated with mortality. PMID- 26374418 TI - Rarely seen complication of motor vehicle accidents: Bilateral globe avulsion. AB - Avulsion of the globe is a rare condition that can occur with severe maxillofacial trauma. A few bilateral cases have been reported. The objective of this study was to present a case of this challenging condition in a 15-year-old male patient who was admitted to the emergency service after a motor vehicle accident. PMID- 26374419 TI - [Multiple small bowel perforations due to Behcet's disease]. AB - Behcet's disease is a chronic, relapsing, multisystemic, idiopathic, and inflammatory disease. A common gastrointestinal site other than the mouth is the ileocecal region. Intestinal ulcers, due to Behcet's disease, can cause perforation. A 19-year-old male patient was admitted to our hospital for Behcet's disease. The patient developed acute abdomen, and laparotomy revealed multiple perforations throughout the terminal ileum. He underwent partial ileum resection. Postoperative period was uneventful, and the patient was discharged. The patient's ileostomy was closed two months after the first operation. He was clinically well during the 16-month follow-up period. This study aimed to report multiple ileum perforations as an unusual complication of Behcet's disease at the time of presentation and review of the current literature of reported cases. PMID- 26374420 TI - Left atrial rupture due to blunt thoracic trauma. AB - Blunt traumatic cardiac rupture is rare and associated with high mortality. The most popular theory of cardiac rupture after blunt thoracic trauma is rapid deceleration with disruption of the atria from their connections to the vena cava and pulmonary veins. In cases with both massive hemothorax and hemopericardium, injury can usually originate from the heart and/or major vessels. Surgical approach through the median sternotomy can provide convenience to repair the defect. In this article, successful treatment with median sternotomy of a 33-year old male case with a rupture of the left atrium after blunt thoracic trauma was reported. PMID- 26374421 TI - Non-traumatic tension gastrothorax in a young lady. AB - Tension gastrothorax is a very rare but potentially fatal clinical condition in which the stomach that herniates through a diaphragmatic defect into the thorax is massively distended by trapped air. It leads to severe symptoms due to the compression of the lung and mediastinum. A 27-year-old female, who had no prior trauma history, applied to the emergency service with the complaint of respiratory disorder, and was consulted by the department of thoracic surgery. Thorax CT revealed presence of gastrothorax in the left hemithorax. Thus, the patient went into cardiopulmonary arrest and was resuscitated. Emergency thoracotomy was performed, abdominal organs were reduced and diaphragmatic defect was repaired. She was discharged on the fifth postoperative day without any complications. PMID- 26374422 TI - Acute retrobulbar haemorrhage: An ophthalmologic emergency for the emergency physician. AB - Acute retrobulbar haemorrhage (ARBH) is a rare ophthalmic emergency observed following blunt eye trauma. Multiple trauma and loss of consciousness can hide symptoms of ARBH. Rapid diagnosis and immediate lateral canthotomy and cantholysis must be performed to prevent permanent visual loss in patients. Medical treatment can be added to surgical therapy. Lateral canthotomy and cantholysis are simple procedures that can be performed by emergency physicians. In this report, it was aimed to present a case with post-traumatic ARBH and provide general knowledge about the diagnosis, follow-up and treatment of ARBH. PMID- 26374423 TI - A systematic review of the evidence on home care reablement services. AB - OBJECTIVE: To determine whether publically funded 'reablement services' have any effect on patient health or use of services. DESIGN: Systematic review of randomized controlled trials and non-randomized studies in which reablement interventions were compared with no care or usual care in people referred to public-funded personal care services. Data sources included: Cochrane Central Register of Controlled Trials, EPOC register of studies, trials registers, Medline, EMBASE, and CINHAL. Searches were from 2000 up to end February 2015. SETTING: Not applicable. PARTICIPANTS: Investigators' definition of the target population for reablement interventions. MAIN OUTCOME MEASURES: Use of publically funded personal care services and dependence in personal activities of daily living. RESULTS: We found no studies fulfilling our inclusion criteria that assessed the effectiveness of reablement interventions. We did note the lack of an agreed understanding of the nature of reablement. CONCLUSIONS: Reablement is an ill-defined intervention targeted towards an ill-defined and potentially highly heterogeneous population/patient group. There is no evidence to suggest it is effective at either of its goals; increasing personal independence or reducing use of personal care services. PMID- 26374424 TI - Cancer cell invasion driven by extracellular matrix remodeling is dependent on the properties of cancer-associated fibroblasts. AB - PURPOSE: As one form of tumor invasion, cancer cells can invade the extracellular matrix (ECM) through tracks that have been physically remodeled by cancer associated fibroblasts (CAFs). However, CAFs are a heterogeneous population with diverse matrix-remodeling capacities. The purpose of this study was to investigate how CAFs with various matrix-remodeling capacities influence cancer cell invasion. METHODS: We established single-cell-derived clones from three primary cultures of CAFs from lung adenocarcinoma patients (Case 1, 5 clones; Case 2, 5 clones; and Case 3, 7 clones). Using a co-culture model, we evaluated the correlations between the number of invaded cancer cells and the remodeling areas generated by CAF clones in each case. RESULTS: When A549 lung adenocarcinoma cells and CAF clones were co-cultured, both the numbers of invaded cancer cells and the remodeling areas generated by the CAF clones varied greatly. The number of invaded cancer cells was moderately and strongly correlated with the remodeling areas generated by each CAF clone originating from Cases 1 and 2 (R(2) value = 0.53 and 0.68, respectively), suggesting that the remodeling areas in the ECM may determine the number of invaded cancer cells. In contrast, the number of invaded cancer cells was not correlated with the remodeling areas generated by CAF clones originating from Case 3, suggesting that factors other than the remodeling areas might determine the number of invading cancer cells. CONCLUSIONS: These findings showed two types of fibroblast-dependent cancer cell invasion that are dependent on and independent of the remodeling areas generated by CAFs. PMID- 26374425 TI - Hydrolysis of Guanosine Triphosphate (GTP) by the Ras.GAP Protein Complex: Reaction Mechanism and Kinetic Scheme. AB - Molecular mechanisms of the hydrolysis of guanosine triphosphate (GTP) to guanosine diphosphate (GDP) and inorganic phosphate (Pi) by the Ras.GAP protein complex are fully investigated by using modern modeling tools. The previously hypothesized stages of the cleavage of the phosphorus-oxygen bond in GTP and the formation of the imide form of catalytic Gln61 from Ras upon creation of Pi are confirmed by using the higher-level quantum-based calculations. The steps of the enzyme regeneration are modeled for the first time, providing a comprehensive description of the catalytic cycle. It is found that for the reaction Ras.GAP.GTP.H2O -> Ras.GAP.GDP.Pi, the highest barriers correspond to the process of regeneration of the active site but not to the process of substrate cleavage. The specific shape of the energy profile is responsible for an interesting kinetic mechanism of the GTP hydrolysis. The analysis of the process using the first-passage approach and consideration of kinetic equations suggest that the overall reaction rate is a result of the balance between relatively fast transitions and low probability of states from which these transitions are taking place. Our theoretical predictions are in excellent agreement with available experimental observations on GTP hydrolysis rates. PMID- 26374426 TI - An epidemiological survey of obstructive sleep apnea-hypopnea syndrome among edentulous population based on modified Berlin questionnaire. AB - PURPOSE: This study aims to investigate the percentage of people in high risk of obstructive sleep apnea-hypopnea syndrome (OSAHS) in edentulous population using the modified Berlin questionnaire (MBQ), to identify sex difference in percentage of edentulous people at high risk of OSAHS, and to analyze the occurrence rate of OSAHS-related symptoms that were not included in the MBQ in this group of people. METHODS: Five hundred and forty patients (edentulous in mandible or maxilla or both) were recruited to participate in this study. Demographic information, nocturnal denture wearing habit, and sleeping posture were recorded. Meanwhile, subjects completed the MBQ in which participants' snoring behavior, wake-time sleepiness or fatigue, and the presence of obesity or hypertension were investigated. RESULTS: Four hundred qualified questionnaires were obtained. According to the MBQ, about 31 % of the subjects were classified at high risk of OSAHS. No significant difference in the percentage of people at high risk of OSAHS was found between male and female groups. Dry or sore mouth and throat, polyuria during sleep, and difficult to fall asleep/easy to wake up showed high occurrence rate equal to or higher than 60 % in the high-risk group. CONCLUSIONS: According to the MBQ, about 31 % of the edentulous population was identified as high risk of OSAHS. Equal attention should be given to elderly edentulous female and male since they are at the same level of risk of developing OSAHS. PMID- 26374427 TI - Circulating Tumor Cells and Recurrence After Primary Systemic Therapy in Stage III Inflammatory Breast Cancer. AB - Inflammatory breast cancer (IBC) is rare and aggressive, with poor survival. While circulating tumor cells (CTCs) predict outcome in non-IBC patients, little data exists regarding their prognostic significance in IBC. This prospective study analyzed blood samples for CTCs from 63 stage III IBC patients to determine if CTCs present after primary systemic chemotherapy predicted relapse. CTC identification was not associated with tumor characteristics, lymph node positivity, or complete pathologic response to systemic therapy. At mean follow up of 38 months, multivariable analysis demonstrated that detection of one or more CTCs predicted shortened relapse-free (log-rank P = 0.005, hazard ratio [HR] = 4.22, 95% confidence interval [CI] = 1.67 to 10.67, Cox P = 0.002) but not overall survival (log-rank P = 0.54, HR = 1.53, 95% CI = 0.41 to 5.79, Cox P = 0.53). All statistical tests were two-sided. In this study, CTCs after primary chemotherapy identified IBC patients at high risk for relapse. PMID- 26374428 TI - Modification of Occupational Exposures on Bladder Cancer Risk by Common Genetic Polymorphisms. AB - Few studies have demonstrated gene/environment interactions in cancer research. Using data on high-risk occupations for 2258 case patients and 2410 control patients from two bladder cancer studies, we observed that three of 16 known or candidate bladder cancer susceptibility variants displayed statistically significant and consistent evidence of additive interactions; specifically, the GSTM1 deletion polymorphism (P interaction <= .001), rs11892031 (UGT1A, P interaction = .01), and rs798766 (TMEM129-TACC3-FGFR3, P interaction = .03). There was limited evidence for multiplicative interactions. When we examined detailed data on a prevalent occupational exposure associated with increased bladder cancer risk, straight metalworking fluids, we also observed statistically significant additive interaction for rs798766 (TMEM129-TACC3-FGFR3, P interaction = .02), with the interaction more apparent in patients with tumors positive for FGFR3 expression. All statistical tests were two-sided. The interaction we observed for rs798766 (TMEM129-TACC3-FGFR3) with specific exposure to straight metalworking fluids illustrates the value of integrating germline genetic variation, environmental exposures, and tumor marker data to provide insight into the mechanisms of bladder carcinogenesis. PMID- 26374429 TI - Neoadjuvant 5-FU or Capecitabine Plus Radiation With or Without Oxaliplatin in Rectal Cancer Patients: A Phase III Randomized Clinical Trial. AB - BACKGROUND: National Surgical Adjuvant Breast and Bowel Project R-04 was designed to determine whether the oral fluoropyrimidine capecitabine could be substituted for continuous infusion 5-FU in the curative setting of stage II/III rectal cancer during neoadjuvant radiation therapy and whether the addition of oxaliplatin could further enhance the activity of fluoropyrimidine-sensitized radiation. METHODS: Patients with clinical stage II or III rectal cancer undergoing preoperative radiation were randomly assigned to one of four chemotherapy regimens in a 2x2 design: CVI 5-FU or oral capecitabine with or without oxaliplatin. The primary endpoint was local-regional tumor control. Time to-event endpoint distributions were estimated using the Kaplan-Meier method. Hazard ratios were estimated from Cox proportional hazard models. All statistical tests were two-sided. RESULTS: Among 1608 randomized patients there were no statistically significant differences between regimens using 5-FU vs capecitabine in three-year local-regional tumor event rates (11.2% vs 11.8%), 5-year DFS (66.4% vs 67.7%), or 5-year OS (79.9% vs 80.8%); or for oxaliplatin vs no oxaliplatin for the three endpoints of local-regional events, DFS, and OS (11.2% vs 12.1%, 69.2% vs 64.2%, and 81.3% vs 79.0%). The addition of oxaliplatin was associated with statistically significantly more overall and grade 3-4 diarrhea (P < .0001). Three-year rates of local-regional recurrence among patients who underwent R0 resection ranged from 3.1 to 5.1% depending on the study arm. CONCLUSIONS: Continuous infusion 5-FU produced outcomes for local-regional control, DFS, and OS similar to those obtained with oral capecitabine combined with radiation. This study establishes capecitabine as a standard of care in the pre-operative rectal setting. Oxaliplatin did not improve the local-regional failure rate, DFS, or OS for any patient risk group but did add considerable toxicity. PMID- 26374430 TI - Functional and cognitive impairment prevention through early physical activity for geriatric hospitalized patients: study protocol for a randomized controlled trial. AB - BACKGROUND: Frail older adults have reduced functional and physiological reserves, rendering them more vulnerable to the effects of hospitalization, which frequently results in failure to recover from the pre-hospitalization functional loss, new disability or even continued functional decline. Alternative care models with an emphasis on multidisciplinary and continuing care units are currently being developed. Their main objective, other than the recovery of the condition that caused admission, is the prevention of functional decline. Many studies on functional decline have discussed the available evidence regarding the effectiveness of acute geriatric units. Despite the theoretical support for the idea that mobility improvement in the hospitalized patient carries multiple benefits, this idea has not been fully translated into clinical practice. METHODS/DESIGN: This study is a randomized clinical trial conducted in the Department of Geriatrics of a tertiary public hospital with 35 beds allocated. Hospitalized patients who meet the inclusion criteria will be randomly assigned to the intervention or control group. The intervention will consist of a multicomponent exercise training programme, which will be composed of supervised progressive resistance exercise training, balance-training, and walking for 5-7 consecutive days. During the training period, patients will be trained in 20 min sessions twice a day (morning and evening). DISCUSSION: Functional and cognitive impairment after and during acute hospitalization in older adults is a major determinant of the later need for health resources. If our hypothesis is correct and shows that a multicomponent, individualized and progressive exercise programme provides effective therapy for improving the functional capacity of acute elderly patients hospitalized for medical pathology versus conventional care, a change of the current system of hospitalization of elderly patients with medical conditions may be justified. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02300896 (Date of registration 19 November 2014). PMID- 26374431 TI - Differential Effects of Pharmacologic and Genetic Modulation of NMDA Receptor Activity on HIV/gp120-Induced Neuronal Damage in an In Vivo Mouse Model. AB - HIV-associated neurocognitive disorder (HAND) consists of motor and cognitive dysfunction in a relatively large percentage of patients with AIDS. Prior work has suggested that at least part of the neuronal and synaptic damage observed in HAND may occur due to excessive stimulation of NMDA-type glutamate receptors (NMDARs). Here, we compared pharmacological and genetic manipulation of NMDAR activity using an improved derivative of the NMDAR antagonist memantine, termed NitroMemantine, and the modulatory NMDAR subunit GluN3A in the HIV/gp120 transgenic (tg) mouse model of HAND. Interestingly, we found that while both NitroMemantine and GluN3A have been shown to inhibit NMDAR activity, NitroMemantine protected synapses in gp120-tg mice, but overexpression of GluN3A augmented the damage. Given recent findings in the field, one explanation for this apparently paradoxical result is the location of the NMDARs primarily affected, with NitroMemantine inhibiting predominantly extrasynaptic pathologically activated NMDARs, but GluN3A disrupting normal NMDAR-mediated neuroprotective activity via inhibition of synaptic NMDARs. PMID- 26374432 TI - Development of the 5-HT2CR-Tango System Combined with an EGFP Reporter Gene. AB - The serotonin 2C receptor (5-HT2CR) is a G-protein-coupled receptor implicated in emotion, feeding, reward, and cognition. 5-HT2CRs are pharmacological targets for mental disorders and metabolic and reward system abnormalities, as alterations in 5-HT2CR expression, RNA editing, and SNPs are involved in these disturbances. To date, 5-HT2CR activity has mainly been measured by quantifying inositol phosphate production and intracellular Ca(2+) release, but these assays are not suitable for in vivo analysis. Here, we developed a 5-HT2CR-Tango assay system, a novel analysis tool of 5-HT2CR activity based on the G-protein-coupled receptor (GPCR) arrestin interaction. With desensitization of activated 5-HT2CR by arrestin, this system converts the 5-HT2CR-arrestin interaction into EGFP reporter gene signal via the LexA transcriptional activation system. For validation of our system, we measured activity of two 5-HT2CR RNA-editing isoforms (INI and VGV) in HEK293 cells transfected with EGFP reporter gene. The INI isoform displayed both higher basal- and 5-HT-stimulated activities than the VGV isoform. Moreover, an inhibitory effect of 5-HT2CR antagonist SB242084 was also detected by 5-HT2CR Tango system. This novel tool is useful for in vitro high-throughput targeted 5 HT2CR drug screening and can be applied to future in vivo brain function studies associated with 5-HT2CRs in transgenic animal models. PMID- 26374433 TI - Oral beclomethasone dipropionate as an initial treatment for stages 1-2 gastrointestinal tract acute graft-versus-host disease following unrelated cord blood transplantation. PMID- 26374435 TI - Prescription Opioid Use Among Seriously Mentally Ill Veterans Nationally in the Veterans Health Administration. AB - Frequent prescription opioid use has been recognized as a growing problem but there have been no studies specifically among veterans with serious mental illness (SMI). National data from the Veterans Health Administration (VHA) during Fiscal Year 2012 show that VHA patients with SMI receive more opioid prescriptions than other veterans. Additionally, high numbers of opioid prescriptions is associated with greater use of anxiolytics/sedative-hypnotics, drug dependence and COPD-all of which pose an increased risk of respiratory depression and falls and warrant substantial caution and improved coordination between mental health and non-mental health prescribers to evaluate risk-benefit tradeoffs. PMID- 26374436 TI - Treatment of Bronchopleural Fistula with Carbolic Acid instilled through Bronchofiberscope in post-pulmonectomy patients. AB - OBJECTIVE: To investigate the efficacy of carbolic acid treatment of bronchopleural fistula (BPF) using bronchofiberscope (BFS) in post-pulmonectomy patients. METHOD: Twelve patients with post-pulmonectomy BPF were enrolled in this study at the Liaoning Tumor Hospital between February 2009 and March 2012. Three patients had BPF after the right pneumonectomy, six patients after left pneumonectomy, one patient after the right middle and low lobectomy and two patients after left upper lobectomy. BPF patients were instilled with 100 % carbolic acid (0.5-1 ml one time every week) through BFS on the mucosal surface around the fistula, and the bubble disappearance was monitored. Treatment was repeated if the bubble remained. RESULTS: No haemorrhage, severe dyspnea or SpO2 declines occurred in all the 12 patients during the bronchoscopic therapy. BPF orifices were closed in five patients after receiving 5 treatments with carbolic acid, 1 patient received 2 treatments, 1 patient was given 3 treatments, 2 patients received 4 treatments and 3 patients were given 7 treatments. Follow-up was conducted for six months following bronchoscopy. The average treatment and fistula closure time were calculated from the data collected as 20 min and 30 days, respectively, and the cure rate was 100 %. Hematoxylin-eosin (HE) staining results revealed that the white flat hyperplasia tissue after carbolic acid treatment was inflammatory granulation tissue. CONCLUSION: Our results revealed that instillation of 100 % carbolic acid with BFS to treat BPF was 100 % effective, which can be a support for post-pulmonectomy BPF. PMID- 26374437 TI - Hidden multiplicity in exploratory multiway ANOVA: Prevalence and remedies. AB - Many psychologists do not realize that exploratory use of the popular multiway analysis of variance harbors a multiple-comparison problem. In the case of two factors, three separate null hypotheses are subject to test (i.e., two main effects and one interaction). Consequently, the probability of at least one Type I error (if all null hypotheses are true) is 14 % rather than 5 %, if the three tests are independent. We explain the multiple-comparison problem and demonstrate that researchers almost never correct for it. To mitigate the problem, we describe four remedies: the omnibus F test, control of the familywise error rate, control of the false discovery rate, and preregistration of the hypotheses. PMID- 26374438 TI - Response to "Plasma Homocysteine Levels and Endothelial Dysfunction in Cerebro- and Cardiovascular Diseases in the Metabolic Syndrome". PMID- 26374439 TI - The Hemodynamics of Stroke: More Than Just Pulse Pressure. PMID- 26374440 TI - Comparison of predictability of Marshall and Rotterdam CT scan scoring system in determining early mortality after traumatic brain injury. AB - BACKGROUND: Marshall computed tomographic (CT) classification is widely used as a predictor of outcome. However, this grading system lacks the following variables, which are found to be useful predictors: subarachnoid/intraventricular hemorrhage, extradural hematoma, and extent of basal cistern compression. A new classification called the Rotterdam grading system, incorporating the above variables, was proposed later. In the original paper, this system was found to have superior discrimination as compared to Marshall grading, however, Rotterdam grading has not been validated widely. We aimed to compare the discriminatory power of both grading systems. METHODS: This is a prospective study of patients with moderate and severe TBI (Glasgow coma scale (GCS) 3-12) who presented to our casualty. All the patients were followed up for 2 weeks to determine early mortality. The discriminatory power of each grading system was determined using area under the receiver operating characteristic curve (AUC). RESULTS: A total of 134 patients, mean age 38.3 (+/-15.7) years, were recruited for study. The overall mortality was 11.2 %. The mean GCS of these patients was 9.6 (+/-2.3). There was good correlation between Marshall and Rotterdam grading, r = 0.68 (significant at 0.01 level). The Marshall CT classification had reasonable discrimination (AUC - 0.707), and Rotterdam grading had good discrimination (AUC 0.681). CONCLUSIONS: Both Marshal and Rotterdam grading systems are good in predicting early mortality after moderate and severe TBI. As the Rotterdam system also includes additional variables like subarachnoid hemorrhage, it may be preferable, particularly in patients with diffuse injury. PMID- 26374441 TI - Validation of the modified Graeb score in aneurysmal subarachnoid hemorrhage. AB - BACKGROUND: Intraventricular hemorrhage (IVH) in patients suffering from aneurysmal subarachnoid hemorrhage (aSAH) is a known negative predictor. Scoring systems like Fisher, Le Roux, and original Graeb score (oGS) are established to quantify the volume of IVH. The aim of this study was to evaluate the validity of the recently introduced modified Graeb score (mGS) in patients with aSAH. METHODS: A retrospective analysis of the validity of the oGS and mGS in 257 aSAH patients was performed to assess and compare the predictive value of hospital mortality, development of CHC, and early functional outcome. RESULTS: In univariate analysis, an increase in either the oGS or mGS was associated with a higher risk for hospital mortality, development of CHC, and poor early functional outcome. The correlation of the oGS and mGS was excellent using Pearson's product moment (r = 0.918; p < 0.001). The predictive value of the oGS was superior to the predictive value of the mGS using receiver operating characteristics and corresponding area under the curve value as there was no statistical significant differences between the scores. CONCLUSIONS: Our study confirms the validity of the recently introduced mGS to quantify the volume of IVH and extends its value in aSAH. However, the mGS offers no additional predictive value for hospital mortality, development of CHC, and poor early functional outcome in patients with aSAH patients compared to the less complex oGS. PMID- 26374442 TI - A review of spontaneous intracranial extradural hematoma in sickle-cell disease. AB - Sickle-cell disease is common among patients of Afro-Caribbean origin. Though it can precipitate neurological conditions, it only rarely causes neurosurgical problems, with very few reported cases. We describe the case of a 7-year-old girl with a background of sickle-cell disease (SCD) brought into an acute neurosurgical unit in extremis, signs of a raised ICP, and with no history of recent trauma. Following further investigations, an acute drop in the hemoglobin and hematocrit levels were noted, with the cause of her presentation being attributed to a sickling crisis causing skull convexity infarction and resulting in spontaneous bilateral extradural hematomas requiring emergency evacuation. We review the current literature and propose the pathophysiological mechanism behind this phenomenon. PMID- 26374443 TI - Specific and helpful intraoperative indocyanine green videoangiography finding of blood blister-like aneurysm of internal carotid artery. AB - BACKGROUND: Blood blister-like aneurysms (BBAs) account for 0.5-2.0 % of ruptured intracranial aneurysms. Because of their rarity, the natural history and pathophysiology of such aneurysms are not fully understood. We present two patients with BBAs treated with Bemsheets-covered clipping and discuss their pathophysiological characteristics, through the intraoperative and specific indocyanine green (ICG) video angiography (VA) findings. CASE REPORT: A 34-year old male and a 53-year-old female were admitted to our emergency room with suddenly reduced levels of consciousness. Brain imaging studies demonstrated a blood blister-like aneurysm of the supraclinoid segment of the right ICA. Craniotomy and an attempt of surgical clipping were performed. ICG-VA showed the filling defect of dye in aneurysm in the operative field. The BBAs were clipped after being covered by Bemsheets (Kawamoto Corporation, Osaka, Japan) and then confirmed by the ICG-VA. Postoperatively, both patients showed transient neurological deficit due to vasospasms and recovered to their normal statuses within a few months after their respective operations. CONCLUSIONS: ICG-VA showed the filling defect of dye in BBAs, which supported that BBAs have been a pseudoaneurysm. In addition, although not routinely recommended in the treatment of BBAs, we believe that Bemsheet-covered clipping is a safe and effective treatment option for BBAs. PMID- 26374444 TI - Antidepressant use in late gestation and risk of postpartum haemorrhage: a retrospective cohort study. AB - OBJECTIVE: To investigate the association between antidepressant use in late gestation and postpartum haemorrhage (PPH). DESIGN: Retrospective cohort study. SETTING: Tertiary teaching hospital in Adelaide, Australia. POPULATION: A total of 30 198 women delivering between 2002 and 2008. METHODS: Relative risks adjusted for maternal sociodemographics and comorbidities (aRRs) were calculated for PPH, comparing women with late-gestation exposure to antidepressants (n = 558), women with a psychiatric illness but no antidepressant use (n = 1292), and women with neither antenatal exposures (n = 28 348). Additional sensitivity analyses were undertaken, examining associations with severe PPH and postpartum anaemia. MAIN OUTCOME MEASURES: The primary outcome was PPH, defined as a recorded blood loss of >=500 mL for vaginal deliveries and >=1000 mL for caesarean sections. Secondary outcomes included severe PPH (>=1000 mL blood loss, irrespective of method of delivery), and the presence of postpartum anaemia (identified from hospital medical records). RESULTS: Compared with unexposed controls, women exposed to antidepressants had an increased risk of PPH (aRR 1.53; 95% confidence interval, 95% CI 1.25-1.86), whereas no increased risk was observed for women with a psychiatric illness but no antidepressant use (aRR 1.04; 95% CI 0.89-1.23). In sensitivity analyses, late gestation antidepressant exposure was associated with an increased risk of severe PPH (aRR 1.84; 95% CI 1.39-2.44), as well as postpartum anaemia (aRR 1.80; 95% CI 1.46-2.22). CONCLUSIONS: Exposure to antidepressants in late gestation was associated with a significantly increased risk of PPH. Although potential confounding by unmeasured factors cannot be ruled out, these findings suggest a direct effect of antidepressant exposure on PPH. TWEETABLE ABSTRACT: Late gestation antidepressant exposure is associated with a significantly increased risk of postpartum haemorrhage. PMID- 26374445 TI - Mitochondrial modulators improve lipid composition and attenuate memory deficits in experimental model of Huntington's disease. AB - 3-Nitropropionic acid (3-NP) is an irreversible inhibitor of succinate dehydrogenase and induces neuropathological changes similar to those observed in Huntington's disease (HD). The objective of the present study was to investigate neuroprotective effect of mitochondrial modulators; alpha-lipoic acid (ALA) and acetyl-L-carnitine (ALCAR) on 3-NP-induced alterations in mitochondrial lipid composition, mitochondrial structure and memory functions. Experimental model of HD was developed by administering 3-NP at sub-chronic doses, twice daily for 17 days. The levels of conjugated dienes, cholesterol and glycolipids were significantly increased, whereas the levels of phospholipids (phosphatidylethanolamine, phosphatidylcholine, phosphatidylserine) including cardiolipin were significantly decreased in the mitochondria isolated from the striatum of 3-NP-treated animals. In addition, the difference in molecular composition of each phospholipid class was also evaluated using mass spectrometry. Mitochondria lipid from 3-NP-treated animals showed increased cholesterol to phospholipid ratio, suggesting decreased mitochondrial membrane fluidity. 3-NP administration also resulted in ultra-structural changes in mitochondria, accompanied by swelling as assessed by transmission electron microscopy. The 3-NP administered animals had impaired spatial memory evaluated using elevated plus maze test. However, combined supplementation with ALA + ALCAR for 21 days normalized mitochondrial lipid composition, improved mitochondrial structure and ameliorated memory impairments in 3-NP-treated animals, suggesting an imperative role of these two modulators in combination in the management of HD. PMID- 26374447 TI - Preregistration student nurses' self-reported preparedness for practice before and after the introduction of a capstone subject. AB - AIMS AND OBJECTIVES: To assess changes in perceptions of confidence and preparedness for practice of preregistration nursing students before and after the introduction of a capstone subject, and factors associated with perceptions of preparedness. BACKGROUND: Preregistration nursing student 'readiness' or 'preparedness' for practice has been highlighted in the literature in recent years, along with employer concerns that university graduate nurses are not work ready. Few studies have examined Australian preregistration nursing students' perceptions of preparedness for clinical practice following their final clinical placement or assessed whether preregistration student nurses' perceptions of preparedness change as the result of undertaking a capstone subject. DESIGN: A capstone subject was introduced at a regional northern Australian university in 2013. Perceptions of preparedness were assessed in two different cohorts of final year nursing students; one of which undertook a capstone subject. METHODS: Two separate cohorts of third year nursing students were surveyed regarding their perceptions of preparedness for practice at the conclusion of their final 240 hour clinical placement. The 2012 cohort did not experience a capstone subject, whereas the 2013 cohort were the first nursing students to experience the new capstone subject. RESULTS: Both cohorts were uncomfortable performing invasive procedures and reported low levels of confidence in the area of professional identity. An overall trend of decreasing confidence as patient assignment size increased was observed for both cohorts, and higher confidence was associated with previous health care experience. Perceptions of preparedness for practice did not increase significantly following the introduction of a capstone subject. CONCLUSIONS: Although Australian undergraduate nursing student report feeling prepared for practice there are areas of knowledge, skills and patient care in which confidence is low. The results of this study highlight the importance of experience in building confidence and competence. RELEVANCE TO CLINICAL PRACTICE: This study highlights that while final year nursing students report feeling prepared for practice there are areas where additional support can be provided. It is recommended that nurse educators and health care facilities tailor their programs to provide support focused on the areas highlighted by this study. PMID- 26374446 TI - Quantitative analysis and clinico-pathological correlations of different dipeptide repeat protein pathologies in C9ORF72 mutation carriers. AB - Hexanucleotide repeat expansion in C9ORF72 is the most common genetic cause of frontotemporal dementia and motor neuron disease. One consequence of the mutation is the formation of different potentially toxic polypeptides composed of dipeptide repeats (DPR) (poly-GA, -GP, -GR, -PA, -PR) generated by repeat associated non-ATG (RAN) translation. While previous studies focusing on poly-GA pathology have failed to detect any clinico-pathological correlations in C9ORF72 mutation cases, recent data from animal and cell culture models suggested that it may be only specific DPR species that are toxic and only when accumulated in certain intracellular compartments. Therefore, we performed a systematic clinico pathological correlative analysis with counting of actual numbers of distinct types of inclusion (neuronal cytoplasmic and intranuclear inclusions, dystrophic neurites) for each DPR protein in relevant brain regions (premotor cortex, lower motor neurons) in a cohort of 35 C9ORF72 mutation cases covering the clinical spectrum from those with pure MND, mixed FTD/MND and pure FTD. While each DPR protein pathology had a similar pattern of anatomical distribution, the total amount of inclusions for each DPR protein varied remarkably (poly-GA > GP > GR > PR/PA), indicating that RAN translation seems to be more effective from sense than from antisense transcripts. Importantly, with the exception of moderate associations for the amount of poly-GA-positive dystrophic neurites with degeneration in the frontal cortex and total burden of poly-GA pathology with disease onset, no relationship was identified for any other DPR protein pathology with degeneration or phenotype. Biochemical analysis revealed a close correlation between insoluble DPR protein species and numbers of visible inclusions, while we did not find any evidence for the presence of soluble DPR protein species. Thus, overall our findings strongly argue against a role of DPR protein aggregation as major and exclusive pathomechanism in C9ORF72 pathogenesis. However, this does not exclude that DPR protein formation might be essential in C9ORF72 pathogenesis in interplay with other consequences associated with the C9ORF72 repeat expansion. PMID- 26374448 TI - Differential effects of leptin on adiponectin expression with weight gain versus obesity. AB - BACKGROUND/OBJECTIVE: Adiponectin exerts beneficial effects by reducing inflammation and improving lipid metabolism and insulin sensitivity. Although the adiponectin level is lower in obese individuals, whether weight gain reduces adiponectin expression in humans is controversial. We sought to investigate the role of weight gain, and consequent changes in leptin, on altering adiponectin expression in humans. METHODS/RESULTS: Forty-four normal-weight healthy subjects were recruited (mean age 29 years; 14 women) and randomized to either gain 5% of body weight by 8 weeks of overfeeding (n=34) or maintain weight (n=10). Modest weight gain of 3.8+/-1.2 kg resulted in increased adiponectin level (P=0.03), whereas weight maintenance resulted in no changes in adiponectin. Further, changes in adiponectin correlated positively with changes in leptin (P=0.0085). In-vitro experiments using differentiated human white preadipocytes showed that leptin increased adiponectin mRNA and protein expression, whereas a leptin antagonist had opposite effects. To understand the role of leptin in established obesity, we compared adipose tissue samples obtained from normal-weight versus obese subjects. We noted, first, that leptin activated cellular signaling pathways and increased adiponectin mRNA in the adipose tissue from normal-weight participants, but did not do so in the adipose tissue from obese participants. Second, we noted that obese subjects had increased caveolin-1 expression, which attenuates leptin-dependent increases in adiponectin. CONCLUSIONS: Modest weight gain in healthy individuals is associated with increases in adiponectin levels, which correlate positively with changes in leptin. In vitro, leptin induces adiponectin expression, which is attenuated by increased caveolin-1 expression. In addition, the adipose tissue from obese subjects shows increased caveolin-1 expression and impaired leptin signaling. This leptin signal impairment may prevent concordant increases in adiponectin levels in obese subjects despite their high levels of leptin. Therefore, impaired leptin signaling may contribute to low adiponectin expression in obesity and may provide a target for increasing adiponectin expression, hence improving insulin sensitivity and cardio-metabolic profile in obesity. PMID- 26374451 TI - [Regional nodal irradiation in early-stage breast cancer with 0-3 positive nodes]. PMID- 26374450 TI - Inverse relationship between a genetic risk score of 31 BMI loci and weight change before and after reaching middle age. AB - BACKGROUND/OBJECTIVE: Genome-wide-association studies have identified numerous body mass index (BMI)-associated variants, but it is unclear how these relate to weight gain in adults at different ages. METHODS: We examined the association of a genetic risk score (GRS), consisting of 31 BMI-associated variants, with an annual weight change (AWC) and a substantial weight gain (SWG) of 10% by comparing self-reported weight at 20 years (y) with baseline weight (mean: 58 y; s.d.: 8 y) in 21407 participants from the Malmo Diet and Cancer Study (MDCS), and comparing baseline weight to weight at follow-up (mean: 73 y; s.d.: 6 y) among 2673 participants. Association between GRS and AWG and SWG was replicated in 4327 GLACIER (Gene x Lifestyle interactions And Complex traits Involved in Elevated disease Risk) participants (mean: 45 y; s.d.: 7 y) with 10 y follow-up. Cohort specific results were pooled by fixed-effect meta-analyses. RESULTS: In MDCS, the GRS was associated with increased AWC (beta: 0.003; s.e: 0.01; P: 7 * 10(-8)) and increased odds for SWG (odds ratio (OR) 1.01 (95% confidence interval (CI): 1.00, 1.02); P: 0.013) per risk-allele from age 20y, but unexpectedly with decreased AWC (beta: -0.006; s.e: 0.002; P: 0.009) and decreased odds for SWG OR 0.96 (95% CI: 0.93, 0.98); P: 0.001) between baseline and follow-up. Effect estimates from age 20 y to baseline differed significantly from those from baseline to follow-up (P: 0.0002 for AWC and P: 0.0001 for SWG). Similar to MDCS, the GRS was associated with decreased odds for SWG OR 0.98 (95% CI: 0.96, 1.00); P: 0.029) from baseline to follow-up in GLACIER. In meta-analyses (n=7000), the GRS was associated with decreased AWC (beta: -0.005; s.e.m. 0.002; P: 0.002) and decreased odds for SWG OR 0.97 (95% CI: 0.96, 0.99); P: 0.001) per risk-allele. CONCLUSIONS: Our results provide convincing evidence for a paradoxical inversed relationship between a high number of BMI-associated risk-alleles and less weight gain during and after middle-age, in contrast to the expected increased weight gain seen in younger age. PMID- 26374449 TI - New insights on the role of the endocannabinoid system in the regulation of energy balance. AB - Within the past 15 years, the endocannabinoid system (ECS) has emerged as a lipid signaling system critically involved in the regulation of energy balance, as it exerts a regulatory control on every aspect related to the search, the intake, the metabolism and the storage of calories. An overactive endocannabinoid cannabinoid type 1 (CB1) receptor signaling promotes the development of obesity, insulin resistance and dyslipidemia, representing a valuable pharmacotherapeutic target for obesity and metabolic disorders. However, because of the psychiatric side effects, the first generation of brain-penetrant CB1 receptor blockers developed as antiobesity treatment were removed from the European market in late 2008. Since then, recent studies have identified new mechanisms of action of the ECS in energy balance and metabolism, as well as novel ways of targeting the system that may be efficacious for the treatment of obesity and metabolic disorders. These aspects will be especially highlighted in this review. PMID- 26374452 TI - Prognostic value of CXCL12 and CXCR4 in inoperable head and neck squamous cell carcinoma. AB - OBJECTIVE: The chemokine CXCL12 and its receptor CXCR4 can affect tumor growth, recurrence, and metastasis. We tested the hypothesis that the CXCL12 and CXCR4 expression influences the prognosis of patients with inoperable head and neck cancer treated with definite radiotherapy or chemoradiotherapy. METHODS: Formalin fixed paraffin-embedded pretreatment tumor tissue from 233 patients with known HPV/p16(INK4A) status was analyzed. CXCL12 and CXCR4 expressions were correlated with pretreatment parameters and survival data by univariate and multivariate Cox regression. RESULTS: CXCL12 was expressed in 43.3 % and CXCR4 in 66.1 % of the samples and both were correlated with HPV/p16(INK4A) positivity. A high CXCL12 expression was associated with increased overall survival (p = 0.036), while a high CXCR4 expression was associated with decreased metastasis-free survival (p = 0.034). CONCLUSION: A high CXCR4 expression could be regarded as a negative prognostic factor in head and neck cancer because it may foster metastatic spread. This may recommend CXCR4 as therapeutic target for combating head and neck cancer metastasis. PMID- 26374453 TI - Emerging Advances in the Management of Cardiac Amyloidosis. AB - Amyloidosis is a disease in which proteins misfold, aggregate into fibrils, and deposit extracellularly disrupting organ architecture and function. There are two main types which affect the heart: light chain (AL) amyloidosis and transthyretin cardiac amyloidosis (ATTR). There is a misconception that cardiac amyloidosis has no effective treatment options. However, over the past decade, there has been extensive research and drug development. Outcomes are improving in AL amyloidosis with evolving chemotherapeutic regimens and novel monoclonal antibodies. In ATTR, therapies that decrease protein production, prevent dissociation, and promote clearance have the potential to slow or even halt a disease which is uniformly fatal. Selected patients may be candidates for heart and/or stem cell transplant and should be promptly referred to an experienced amyloid program. Herein, we discuss the emerging advances for the treatment of cardiac amyloidosis. PMID- 26374454 TI - What Are Optimal Blood Pressure Targets for Patients with Hypertension and Chronic Kidney Disease? AB - To maximize the risk benefit ratio of blood pressure control in people with chronic kidney diseases (CKD), a number of guidelines provide recommendations on optimal blood pressure (BP) targets in CKD. This review examines these guidelines, their supporting evidence base, and generalizability and limitations of current standards of care. Over the years, the BP targets are liberalized. They now focus on the usual BP target of <140/90 mmHg. In the elderly, where guidelines call for a target of <150/90 mmHg in the general population, the recommendations provide room for the clinician to tailor therapy. Among those with albuminuria of >300 mg/g creatinine, low-quality evidence suggests targeting BP to <130/90 mmHg. Individualization of BP lowering is a key based on comorbid conditions, response to treatment, and level of kidney function. Consideration of out of clinic BP monitoring either implemented by home BP recordings or ambulatory BP measurements may enhance BP control. PMID- 26374455 TI - The Year Embolectomy Won: a Review of Five Trials Assessing the Efficacy of Mechanical Intervention in Acute Stroke. AB - Embolectomy with stentriever devices is the newest treatment for acute stroke. Since 1995, treatment of acute stroke has been limited to a 4.5-h window with the use of intravenous tissue plasminogen activator (tPA). Five articles have been published in 2015 with the results supporting the paired treatment of tPA and embolectomy. This has also expanded the treatment window to greater than 4.5 h and produced evidence which will guide selection of patients that will benefit most from this therapy. This article will compare and contrast this most recent evidence. PMID- 26374458 TI - Indian girls born in states with sex selection are less malnourished, finds study. PMID- 26374456 TI - Dopaminergic mediation of the discriminative stimulus functions of modafinil in rats. AB - RATIONALE: Modafinil is a wake-promoting drug with FDA approval for the treatment of excessive daytime sleepiness that has been prescribed for ADHD and recently assessed as a potential treatment for psychostimulant dependence. Previous research indicates that modafinil modestly increases locomotor activity and produces similar discriminative stimulus effects to psychostimulants in rodents, although the subjective effects of modafinil are reportedly distinct from those of cocaine or amphetamine in humans with a history of psychostimulant abuse. OBJECTIVES: The current study employed drug discrimination procedures in rats to examine the pharmacological actions contributing to modafinil's discriminative stimulus functions. METHODS: Eight male Sprague-Dawley rats were trained to discriminate intragastric administration of 256 mg/kg modafinil from vehicle (5% arabic gum) under a FR 20 schedule of food reinforcement. Substitution tests were conducted with various dopaminergic agents (d-amphetamine, cocaine, PNU-91356A, GBR 12909, methylphenidate) and nondopaminergic agents (nicotine, ethanol). Antagonist tests were conducted with the selective D1 antagonist, SCH 39166, and the nonselective D2 antagonist, haloperidol. RESULTS: Rats trained to discriminate modafinil displayed complete stimulus generalization to cocaine, methylphenidate, and GBR 12909 and the discrimination was completely blocked by both SCH 39166 and haloperidol. Evidence for significant partial substitution was obtained with d-amphetamine, PNU-91356A, and nicotine. CONCLUSIONS: Results strongly support the role of dopaminergic mechanisms in the discriminative stimulus functions of modafinil, although further evaluation regarding the contribution of other neurotransmitter systems to these effects should be continued. The findings are discussed in light of clinical research efforts with modafinil as a treatment for psychostimulant dependence. PMID- 26374457 TI - Excitotoxic and Radiation Stress Increase TERT Levels in the Mitochondria and Cytosol of Cerebellar Purkinje Neurons. AB - Telomerase reverse transcriptase (TERT) is the catalytic subunit of telomerase, an enzyme that elongates telomeres at the ends of chromosomes during DNA replication. Recently, it was shown that TERT has additional roles in cell survival, mitochondrial function, DNA repair, and Wnt signaling, all of which are unrelated to telomeres. Here, we demonstrate that TERT is enriched in Purkinje neurons, but not in the granule cells of the adult mouse cerebellum. TERT immunoreactivity in Purkinje neurons is present in the nucleus, mitochondria, and cytoplasm. Furthermore, TERT co-localizes with mitochondrial markers, and immunoblot analysis of protein extracts from isolated mitochondria and synaptosomes confirmed TERT localization in mitochondria. TERT expression in Purkinje neurons increased significantly in response to two stressors: a sub lethal dose of X-ray radiation and exposure to a high glutamate concentration. While X-ray radiation increased TERT levels in the nucleus, glutamate exposure elevated TERT levels in mitochondria. Our findings suggest that in mature Purkinje neurons, TERT is present both in the nucleus and in mitochondria, where it may participate in adaptive responses of the neurons to excitotoxic and radiation stress. PMID- 26374459 TI - Volatilisation of pesticides under field conditions: inverse modelling and pesticide fate models. AB - BACKGROUND: A substantial fraction of the applied crop protection products on crops is lost to the atmosphere. Models describing the prediction of volatility and potential fate of these substances in the environment have become an important tool in the pesticide authorisation procedure at the EU level. The main topic of this research is to assess the rate and extent of volatilisation of ten pesticides after application on field crops. RESULTS: For eight of the ten pesticides, the volatilisation rates modelled with PEARL (Pesticide Emission Assessment at Regional and Local scales) corresponded well to the calculated rates modelled with ADMS (Atmospheric Dispersion Modelling System). For the other pesticides, large differences were found between the models. Formulation might affect the volatilisation potential of pesticides. Increased leaf wetness increased the volatilisation of propyzamide and trifloxystrobin at the end of the field trial. The reliability of pesticide input parameters, in particular the vapour pressure, is discussed. CONCLUSION: Volatilisation of propyzamide, pyrimethanil, chlorothalonil, diflufenican, tolylfluanid, cyprodinil and E- and Z dimethomorph from crops under realistic environmental conditions can be modelled with the PEARL model, as corroborated against field observations. Suggested improvements to the volatilisation component in PEARL should include formulation attributes and leaf wetness at the time of pesticide application. (c) 2015 Society of Chemical Industry. PMID- 26374460 TI - A Bayesian Approach to Inferring Rates of Selfing and Locus-Specific Mutation. AB - We present a Bayesian method for characterizing the mating system of populations reproducing through a mixture of self-fertilization and random outcrossing. Our method uses patterns of genetic variation across the genome as a basis for inference about reproduction under pure hermaphroditism, gynodioecy, and a model developed to describe the self-fertilizing killifish Kryptolebias marmoratus. We extend the standard coalescence model to accommodate these mating systems, accounting explicitly for multilocus identity disequilibrium, inbreeding depression, and variation in fertility among mating types. We incorporate the Ewens sampling formula (ESF) under the infinite-alleles model of mutation to obtain a novel expression for the likelihood of mating system parameters. Our Markov chain Monte Carlo (MCMC) algorithm assigns locus-specific mutation rates, drawn from a common mutation rate distribution that is itself estimated from the data using a Dirichlet process prior model. Our sampler is designed to accommodate additional information, including observations pertaining to the sex ratio, the intensity of inbreeding depression, and other aspects of reproduction. It can provide joint posterior distributions for the population-wide proportion of uniparental individuals, locus-specific mutation rates, and the number of generations since the most recent outcrossing event for each sampled individual. Further, estimation of all basic parameters of a given model permits estimation of functions of those parameters, including the proportion of the gene pool contributed by each sex and relative effective numbers. PMID- 26374461 TI - Meandering right pulmonary vein associated with severe and progressive "idiopathic-like" pulmonary hypertensive vascular disease. AB - Congenital anomalies of the pulmonary veins are rare. Meandering right pulmonary vein, considered a part of the Scimitar syndrome spectrum, is often an incidental finding during chest imaging. We present the case of a 4-year-old girl diagnosed with meandering pulmonary vein, who developed pulmonary hypertensive disease with an aggressive course, in spite of absence of hypoxia or elevated pulmonary wedge pressure. PMID- 26374463 TI - Tumors and mitochondrial respiration: a neglected connection. AB - For decades, tumor cells have been considered defective in mitochondrial respiration due to their dominant glycolytic metabolism. However, a growing body of evidence is now challenging this assumption, and also implying that tumors are metabolically less homogeneous than previously supposed. A small subpopulation of slow-cycling cells endowed with tumorigenic potential and multidrug resistance has been isolated from different tumors. Deep metabolic characterization of these tumorigenic cells revealed their dependency on mitochondrial respiration versus glycolysis, suggesting the existence of a common metabolic program active in slow cycling cells across different tumors. These findings change our understanding of tumor metabolism and also highlight new vulnerabilities that can be exploited to eradicate cancer cells responsible for tumor relapse. PMID- 26374464 TI - Real-time Imaging of the Resection Bed Using a Handheld Probe to Reduce Incidence of Microscopic Positive Margins in Cancer Surgery. AB - Wide local excision (WLE) is a common surgical intervention for solid tumors such as those in melanoma, breast, pancreatic, and gastrointestinal cancer. However, adequate margin assessment during WLE remains a significant challenge, resulting in surgical reinterventions to achieve adequate local control. Currently, no label-free imaging method is available for surgeons to examine the resection bed in vivo for microscopic residual cancer. Optical coherence tomography (OCT) enables real-time high-resolution imaging of tissue microstructure. Previous studies have demonstrated that OCT analysis of excised tissue specimens can distinguish between normal and cancerous tissues by identifying the heterogeneous and disorganized microscopic tissue structures indicative of malignancy. In this translational study involving 35 patients, a handheld surgical OCT imaging probe was developed for in vivo use to assess margins both in the resection bed and on excised specimens for the microscopic presence of cancer. The image results from OCT showed structural differences between normal and cancerous tissue within the resection bed following WLE of the human breast. The ex vivo images were compared with standard postoperative histopathology to yield sensitivity of 91.7% [95% confidence interval (CI), 62.5%-100%] and specificity of 92.1% (95% CI, 78.4% 98%). This study demonstrates in vivo OCT imaging of the resection bed during WLE with the potential for real-time microscopic image-guided surgery. PMID- 26374465 TI - Spectroscopic studies of lanthanide complexes of varying nuclearity based on a compartmentalised ligand. AB - The synthesis, characterization and solid-state luminescence spectroscopy of mononuclear (f), heterodinuclear (d-f) and heterotrinuclear (d-f-d) coordination compounds with the compartmental ligand N,N'-bis(3-hydroxyl salicylidene)benzene 1,2-diamine (H2L) are reported. The trivalent lanthanide ions Nd(III), Sm(III), Eu(III), Gd(III), Tb(III) and Dy(III) as single metal centres or in combination with either Zn(II) or Ni(II) were coordinated. Compounds are characterised by elemental analyses, IR, 1D and 2D solution (1)H and (13)C NMR spectroscopy, measurements of magnetic moments and solid state UV-Vis-NIR reflectance, luminescence and Raman spectroscopy techniques. Crystal structures of the dinuclear compounds [SmZn(O2NO)3(L)(OH2)].EtOH and [DyZn(O2NO)2(Cl)(L)(EtOH)].3EtOH and the trinuclear compound [TbZn2(L)2(Cl)2(OH2)](NO3).EtOH are presented, where samarium(iii) displays a coordination number of ten, with a bicapped cubic geometry, while for the dysprosium compound a nine-coordinated environment with a tricapped trigonal prismatic geometry is shown. Their crystals belong to the triclinic system and the P1[combining macron] space group. The coordination number for terbium(iii) in the trinuclear complex is nine, with a tricapped trigonal prismatic geometry, and its crystal belongs to the monoclinic system, space group C2/c. For these three compounds, the zinc ion stabilises a penta-coordinated environment with square pyramid geometry. All mononuclear and dinuclear compounds are neutral, whereas the trinuclear complexes are ionic. The results of DFT theoretical calculations for the ligand (H2L) are used to assign the ligand singlet and triplet excited state energy levels. Luminescence studies of the neodymium compounds indicate that the ligand is a sensitizer for NIR emitters. PMID- 26374466 TI - Protective role of ALDH2 against acetaldehyde-derived DNA damage in oesophageal squamous epithelium. AB - Acetaldehyde is an ethanol-derived definite carcinogen that causes oesophageal squamous cell carcinoma (ESCC). Aldehyde dehydrogenase 2 (ALDH2) is a key enzyme that eliminates acetaldehyde, and impairment of ALDH2 increases the risk of ESCC. ALDH2 is produced in various tissues including the liver, heart, and kidney, but the generation and functional roles of ALDH2 in the oesophagus remain elusive. Here, we report that ethanol drinking increased ALDH2 production in the oesophagus of wild-type mice. Notably, levels of acetaldehyde-derived DNA damage represented by N(2)-ethylidene-2'-deoxyguanosine were higher in the oesophagus of Aldh2-knockout mice than in wild-type mice upon ethanol consumption. In vitro experiments revealed that acetaldehyde induced ALDH2 production in both mouse and human oesophageal keratinocytes. Furthermore, the N(2)-ethylidene-2' deoxyguanosine levels increased in both Aldh2-knockout mouse keratinocytes and ALDH2-knockdown human keratinocytes treated with acetaldehyde. Conversely, forced production of ALDH2 sharply diminished the N(2)-ethylidene-2'-deoxyguanosine levels. Our findings provide new insight into the preventive role of oesophageal ALDH2 against acetaldehyde-derived DNA damage. PMID- 26374467 TI - Application of nephrostomy tubes with balloon after percutaneous nephrolithotomy: A randomized controlled clinical trial. AB - OBJECTIVE: To evaluate the effect of nephrostomy tubing with balloon on postoperative hemorrhage after percutaneous nephrolithotomy. METHODS: A total of 284 patients with upper urinary calculi were enrolled for blocked randomization with 71 blocks and block length of 4. The experimental group consisted of 143 patients receiving 14-Fr silicone tubing with balloon, and the control group consisted of 141 patients receiving 14-Fr silicone tubing without balloon. One patient in the control group developed intraoperative bleeding as a result of calyceal laceration, and was reassigned to the experimental group receiving nephrostomy tubing with balloon. RESULTS: Postoperative drop in hemoglobin level at 3 days was significantly less in the experimental group (3.31 +/- 2.85 g/L) compared with the control group (5.14 +/- 3.43 g/L) (P < 0.001). The duration of gross hematuria, defined by urine with visible light or bright red color (2.73 +/ 1.59 days vs. 3.55 +/- 2.09 days, P < 0.001), and the incidence of postoperative extravasation (22/143 vs. 38/141, P < 0.05) for patients in the experimental group (implanted with 14-Fr silicone tubing with balloon) were significantly lower compared with the control group. CONCLUSION: Use of indwelling nephrostomy tubes with balloon after percutaneous nephrolithotomy can reduce blood loss. Further consideration for more widespread adoption of this type of tubing to limit perioperative bleeding complications is warranted. PMID- 26374468 TI - Effect evaluation of a heated ambulance mattress-prototype on thermal comfort and patients' temperatures in prehospital emergency care--an intervention study. AB - BACKGROUND: The ambulance milieu does not offer good thermal comfort to patients during the cold Swedish winters. Patients' exposure to cold temperatures combined with a cold ambulance mattress seems to be the major factor leading to an overall sensation of discomfort. There is little research on the effect of active heat delivered from underneath in ambulance care. Therefore, the aim of this study was to evaluate the effect of an electrically heated ambulance mattress-prototype on thermal comfort and patients' temperatures in the prehospital emergency care. METHODS: A quantitative intervention study on ambulance care was conducted in the north of Sweden. The ambulance used for the intervention group (n=30) was equipped with an electrically heated mattress on the regular ambulance stretcher whereas for the control group (n=30) no active heat was provided on the stretcher. Outcome variables were measured as thermal comfort on the Cold Discomfort Scale (CDS), subjective comments on cold experiences, and finger, ear and air temperatures. RESULTS: Thermal comfort, measured by CDS, improved during the ambulance transport to the emergency department in the intervention group (p=0.001) but decreased in the control group (p=0.014). A significant higher proportion (57%) of the control group rated the stretcher as cold to lie down compared to the intervention group (3%, p<0.001). At arrival, finger, ear and compartment air temperature showed no statistical significant difference between groups. Mean transport time was approximately 15 minutes. CONCLUSIONS: The use of active heat from underneath increases the patients' thermal comfort and may prevent the negative consequences of cold stress. PMID- 26374470 TI - Role of MRI in the staging of breast cancer patients: does histological type and molecular subtype matter? AB - OBJECTIVE: To assess the role of MRI in the pre-operative staging of patients with different histological types and molecular subtypes of breast cancer, by the assessment of the dimensions of the main tumour and identification of multifocal and/or multicentric disease. METHODS: The study included 160 females diagnosed with breast cancer who underwent breast MRI for pre-operative staging. The size of the primary tumour evaluated by MRI was compared with the pathology (gold standard) using the Pearson's correlation coefficient (r). The presence of multifocal and/or multicentric disease was also evaluated. RESULTS: The mean age of patients was 52.6 years (range 30-81 years). Correlation between the largest dimension of the main tumour measured by MRI and pathology was worse for non special type/invasive ductal carcinoma than for other histological types and was better for luminal A and triple-negative than for luminal B and Her-2 molecular subtypes. Multifocal and/or multicentric disease was present in 48 patients (30.0%), and it was more common in breast carcinomas classified as Her-2 molecular subtype. There was no statistically significant difference in the frequency of multifocal and/or multicentric tumours identified only by MRI in relation to histological type or molecular subtype. CONCLUSION: The results of this retrospective study demonstrated that histological types and molecular subtypes might influence the MRI assessment of breast cancers, especially in the evaluation of tumour size. ADVANCES IN KNOWLEDGE: The real benefit of MRI for treatment planning in patients with breast cancer may be different according to the histological type and molecular subtype. PMID- 26374471 TI - Comparison of mental-status scales for predicting mortality on the general wards. AB - BACKGROUND: Altered mental status is a significant predictor of mortality in inpatients. Several scales exist to characterize mental status, including the AVPU (Alert, responds to Voice, responds to Pain, Unresponsive) scale, which is used in many early-warning scores in the general-ward setting. The use of the Glasgow Coma Scale (GCS) and Richmond Agitation Sedation Scale (RASS) is not well established in this population. OBJECTIVE: To compare the accuracies of AVPU, GCS, and RASS for predicting inpatient mortality. DESIGN: Retrospective cohort study. SETTING: Single, urban, academic medical center. PARTICIPANTS: Adult inpatients on the general wards. MEASUREMENTS: Nurses recorded GCS and RASS on consecutive adult hospitalizations. AVPU was extracted from the eye subscale of the GCS. We compared the accuracies of each scale for predicting in-hospital mortality within 24 hours of a mental-status observation using area under the receiver operating characteristic curves (AUC). RESULTS: There were 295,974 paired observations of GCS and RASS obtained from 26,873 admissions; 417 (1.6%) resulted in in-hospital death. GCS and RASS more accurately predicted mortality than AVPU (AUC 0.80 and 0.82, respectively, vs 0.73; P < 0.001 for both comparisons). Simultaneous use of GCS and RASS produced an AUC of 0.85 (95% confidence interval: 0.82-0.87, P < 0.001 when compared to all 3 scales). CONCLUSIONS: In ward patients, both GCS and RASS were significantly more accurate predictors of mortality than AVPU. In addition, combining GCS and RASS was more accurate than any scale alone. Routine tracking of GCS and/or RASS on general wards may improve the accuracy of detecting clinical deterioration. PMID- 26374472 TI - Differentiation and function of group 3 innate lymphoid cells, from embryo to adult. AB - Group 3 innate lymphoid cells (ILC3) represent a heterogeneous population of cells that share the nuclear hormone receptor RORgammat (retinoic acid receptor related orphan receptor gammat) as a master regulator for differentiation and function. ILC3 can be divided into two major subsets based on the cell surface expression of the natural cytotoxicity receptor (NCR), NKp46. A subset of NCR(-) ILC3 includes the previously known lymphoid-tissue inducer cells that are essential for the embryonic formation of peripheral lymph nodes and Peyer's patches. After birth, the NCR(-) and NCR(+) ILC3 contribute to the maintenance of health but also to inflammation in mucosal tissues. This review will describe the differentiation pathways of ILC3, their involvement in the development of the adaptive immune system and their role in the establishment and maintenance of gut immunity. PMID- 26374473 TI - The cytosolic or the mitochondrial glutathione peroxidase-type tryparedoxin peroxidase is sufficient to protect procyclic Trypanosoma brucei from iron mediated mitochondrial damage and lysis. AB - African trypanosomes express three virtually identical glutathione peroxidase (Px)-type enzymes that occur in the cytosol (Px I and II) and mitochondrion (Px III) and detoxify fatty acid-derived hydroperoxides. Selective deletion of the genes revealed that procyclic Trypanosoma brucei lacking either the cytosolic or mitochondrial enzyme proliferate nearly as wild-type parasites, whereas the knockout of the complete genomic locus is lethal. Flow cytometry and immunofluorescence analyses revealed that the Px I-III-deficient parasites lose their mitochondrial membrane potential, which is followed by a loss of the lysosomal signal but not the glycosomal one. Mitochondrial damage and cell lysis are prevented by Trolox, ubiquinone derivatives and the iron chelator deferoxamine, whereas starch-deferoxamine is inefficient. In glucose-rich medium, cell death is attenuated suggesting that oxidants generated by the respiratory chain contribute to the lethal phenotype. Thus, the Px-type peroxidases protect procyclic cells from an iron-mediated oxidative membrane damage that originates at the mitochondrion. This contrasts with the situation in bloodstream cells, where the lysosome is the primarily affected organelle. Strikingly, either the cytosolic or the mitochondrial form of the peroxidases is required and sufficient to protect the mitochondrion and prevent cell lysis. PMID- 26374476 TI - Luteinizing hormone induces ovulation via tumor necrosis factor alpha-dependent increases in prostaglandin F2alpha in a nonmammalian vertebrate. AB - Ovulation is induced by the preovulatory surge of luteinizing hormone (LH) that acts on the ovary and triggers the rupture of the preovulatory ovarian follicle by stimulating proteolysis and apoptosis in the follicle wall, causing the release of the mature oocyte. The pro-inflammatory cytokine tumor necrosis factor alpha (TNFalpha) and prostaglandin (PG) F2alpha (PGF2alpha) are involved in the control of ovulation but their role mediating the pro-ovulatory actions of LH is not well established. Here we show that Lh induces PGF2alpha synthesis through its stimulation of Tnfalpha production in trout, a primitive teleost fish. Recombinant trout Tnfalpha (rTnfalpha) and PGF2alpha recapitulate the stimulatory in vitro effects of salmon Lh (sLh) on contraction, proteolysis and loss of cell viability in the preovulatory follicle wall and, finally, ovulation. Furthermore, all pro-ovulatory actions of sLh are blocked by inhibition of Tnfalpha secretion or PG synthesis and all actions of rTnfalpha are blocked by PG synthesis inhibitors. Therefore, we provide evidence that the Tnfalpha-dependent increase in PGF2alpha production is necessary for the pro-ovulatory actions of Lh. The results from this study shed light onto the mechanisms underlying the pro ovulatory actions of LH in vertebrates and may prove important in clinical assessments of female infertility. PMID- 26374477 TI - Biosynthesis of the Fluorinated Natural Product Nucleocidin in Streptomyces calvus Is Dependent on the bldA-Specified Leu-tRNA(UUA) Molecule. AB - Nucleocidin is one of the very few natural products known to contain fluorine. Mysteriously, the nucleocidin producer Streptomyces calvus ATCC 13382 has not been observed to synthesize the compound since its discovery in 1956. Here, we report that complementation of S. calvus ATCC 13382 with a functional bldA encoded Leu-tRNA(UUA) molecule restores the production of nucleocidin. Nucleocidin was detected in culture extracts by (19) F NMR spectroscopy, HPLC-ESI MS, and HPLC-continuum source molecular absorption spectroscopy for fluorine specific detection. The molecule was purified from a large-scale culture and definitively characterized by NMR spectroscopy and high-resolution MS. The nucleocidin biosynthetic gene cluster was identified by the presence of genes encoding the 5'-O-sulfamate moiety and confirmed by gene disruption. Two of the genes within the nucleocidin biosynthetic gene cluster contain TTA codons, thus explaining the dependence on bldA and resolving a 60-year-old mystery. PMID- 26374478 TI - White Matter Injury After Subarachnoid Hemorrhage: Role of Blood-Brain Barrier Disruption and Matrix Metalloproteinase-9. AB - BACKGROUND AND PURPOSE: We recently observed early white matter injury after experimental subarachnoid hemorrhage (SAH), but the underlying mechanisms are uncertain. This study investigated the potential role of matrix metalloproteinase (MMP)-9 in blood-brain barrier (BBB) disruption and consequent white matter injury. METHODS: SAH was induced by endovascular perforation in adult male mice. The following 3 experiments were devised: (1) mice underwent magnetic resonance imaging at 24 h after SAH and were euthanized to determine BBB disruption and MMP 9 activation in white matter; (2) to investigate the role of MMP-9 in BBB disruption, lesion volumes on magnetic resonance imaging were compared between wild-type (WT) and MMP-9 knockout (MMP-9-/-) mice at 24 h after SAH; (3) WT and MMP-9-/- mice underwent magnetic resonance imaging at 1 and 8 days after SAH to detect time-dependent changes in brain injury. Brains were used to investigate myelin integrity in white matter. RESULTS: In WT mice with SAH, white matter showed BBB disruption (albumin leakage) and T2 hyperintensity on magnetic resonance imaging. MMP-9 activity was elevated at 24 h after SAH. MMP-9-/- mice had less white matter T2 hyperintensity after SAH than WT mice. At 8 days after SAH, WT mice had decreased myelin integrity and MMP-9-/- mice developed less white matter injury. CONCLUSIONS: SAH causes BBB disruption and consequent injury in white matter. MMP-9 plays an important role in those pathologies and could be a therapeutic target for SAH-induced white matter injury. PMID- 26374480 TI - A Multicomponent Behavioral Intervention to Reduce Stroke Risk Factor Behaviors: The Stroke Health and Risk Education Cluster-Randomized Controlled Trial. AB - BACKGROUND AND PURPOSE: The Stroke Health and Risk Education Project was a cluster-randomized, faith-based, culturally sensitive, theory-based multicomponent behavioral intervention trial to reduce key stroke risk factor behaviors in Hispanics/Latinos and European Americans. METHODS: Ten Catholic churches were randomized to intervention or control group. The intervention group received a 1-year multicomponent intervention (with poor adherence) that included self-help materials, tailored newsletters, and motivational interviewing counseling calls. Multilevel modeling, accounting for clustering within subject pairs and parishes, was used to test treatment differences in the average change since baseline (ascertained at 6 and 12 months) in dietary sodium, fruit and vegetable intake, and physical activity, measured using standardized questionnaires. A priori, the trial was considered successful if any one of the 3 outcomes was significant at the 0.05/3 level. RESULTS: Of 801 subjects who consented, 760 completed baseline data assessments, and of these, 86% completed at least one outcome assessment. The median age was 53 years; 84% subjects were Hispanic/Latino; and 64% subjects were women. The intervention group had a greater increase in fruit and vegetable intake than the control group (0.25 cups per day [95% confidence interval: 0.08, 0.42], P=0.002), a greater decrease in sodium intake (-123.17 mg/d [-194.76, -51.59], P=0.04), but no difference in change in moderate- or greater-intensity physical activity (-27 metabolic equivalent-minutes per week [-526, 471], P=0.56). CONCLUSIONS: This multicomponent behavioral intervention targeting stroke risk factors in predominantly Hispanics/Latinos was effective in increasing fruit and vegetable intake, reaching its primary end point. The intervention also seemed to lower sodium intake. Church-based health promotions can be successful in primary stroke prevention efforts. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01378780. PMID- 26374481 TI - n-3 Polyunsaturated Fatty Acids Reduce Neonatal Hypoxic/Ischemic Brain Injury by Promoting Phosphatidylserine Formation and Akt Signaling. AB - BACKGROUND AND PURPOSE: Omega-3 polyunsaturated fatty acids (n-3 PUFAs) attenuate neonatal hypoxic/ischemic (H/I) brain damage, but the underlying mechanisms are not fully understood. This study tested the hypothesis that n-3 PUFAs enhance Akt dependent prosurvival signaling by promoting the biosynthesis of phosphatidylserine in neuronal cell membranes. METHODS: Dietary n-3 PUFA supplementation was initiated on the second day of pregnancy in dams. H/I was induced in 7-day-old rat pups by ipsilateral common carotid artery occlusion followed by hypoxia (8% oxygen for 2.5 hours). Neurological outcomes, brain tissue loss, cell death, and the activation of signaling events were assessed after H/I. The effects of n-3 PUFAs (docosahexaenoic acid and eicosapentaenoic acid) on oxygen-glucose deprivation-induced cell death and the underlying mechanism of protection were also examined in primary cortical neuron cultures. RESULTS: n-3 PUFAs reduced brain tissue loss at 7 days after H/I and improved neurological outcomes, whereas inhibition of PI3K/Akt signaling by LY294002 partially abrogated this neuroprotective effect. Docosahexaenoic acid/eicosapentaenoic acid also prevented ischemic neuronal death through the Akt prosurvival pathway in vitro. Furthermore, docosahexaenoic acid/eicosapentaenoic acid increased the production of phosphatidylserine, the major membrane-bound phospholipids, after ischemia both in vitro and in vivo. A reduction in membrane phosphatidylserine by shRNA-mediated knockdown of phosphatidylserine synthetase-1 attenuated Akt activation and neuronal survival after docosahexaenoic acid/eicosapentaenoic acid treatment in the oxygen-glucose deprivation model. CONCLUSIONS: n-3 PUFAs robustly protect against H/I-induced brain damage in neonates by activating Akt prosurvival pathway in compromised neurons. In addition, n-3 PUFAs promote the formation of membrane phosphatidylserine, thereby promoting Akt activity and improving cellular survival. PMID- 26374482 TI - Multidomain Lifestyle Interventions for the Prevention of Cognitive Decline After Ischemic Stroke: Randomized Trial. AB - BACKGROUND AND PURPOSE: Cognitive impairment occurs in <=30% of all stroke survivors. However, effective therapies aimed at preventing poststroke cognitive decline are lacking. We assessed the efficacy of a multidomain intervention on preventing cognitive decline after stroke. METHODS: In this randomized, observer blind trial patients were recruited within 3 months after an acute stroke in 5 Austrian neurological centers. Patients were assigned to a 24-month lifestyle based multidomain intervention or standard stroke care. Primary outcomes were the cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS-cog) and occurrence of cognitive decline in the composite scores of at least 2 of 5 cognitive domains at 24 months. RESULTS: A total of 101 patients were randomized into multi-intervention and 101 into standard care during June 2010 and November 2012. Of them, 76 patients in the intervention group and 83 in the control group were included in the final intention-to-treat analysis. At 24 months, 8 of 76 (10.5%) patients in the intervention group and 10 of 83 (12.0%) patients in the control group showed cognitive decline corresponding to a relative risk reduction of 0.874 (95% confidence interval, 0.364-2.098). The change in ADAS-cog from baseline to 24 months was not different either (median 0 [IQR, -1 to 2] in both groups; P=0.808). CONCLUSIONS: This trial found no benefit of 24-month multidomain intervention with focus on improvement in lifestyle and vascular risk factors on the incidence of poststroke cognitive decline in comparison with standard stroke care. Studies with a larger sample size are needed. CLINICAL TRIAL REGISTRATION: URL: http://clinicaltrials.gov. Unique identifier: NCT01109836. PMID- 26374483 TI - Optimizating Clot Retrieval in Acute Stroke: The Push and Fluff Technique for Closed-Cell Stentrievers. AB - BACKGROUND AND PURPOSE: We aimed to investigate the safety and efficacy of the Push and Fluff technique (PFT) as compared with the standard unsheathing technique for closed-cell stent retrievers in acute ischemic stroke. METHODS: Acute ischemic stroke thrombectomy database was analyzed (September 2010 to January 2015) with the Trevo Retriever as a primary strategy. The PFT was compared with our internal standard unsheathing technique and with the Trevo Versus Merci Retrievers for Thrombectomy Revascularization of Large Vessel Occlusions in Acute Ischemic Stroke 2 (TREVO2) trial. Additionally, a silicon flow model was used to compare cell size/configuration, wall apposition/device diameter, and degree of foreshortening/device length across the 2 techniques. RESULTS: One hundred fifty-one out of 662 patients qualified for the study. The PFT (n=71) was associated with higher rates of first-pass reperfusion (54% versus 35%, P=0.03; 54% versus 32.6%, P<0.01), lower number of passes (1.3+/-0.8 versus 1.8+/-1.0, P<0.01; 1.7+/-1.0 versus 2.4+/-1.6, P<0.01), and higher rates of modified treatment in cerebral ischemia-3 reperfusion (58% versus 40%, P=0.03; 58% versus 14%, P<0.01) as compared with the standard unsheathing technique (n=81) and the TREVO2 Trevo arm (n=88), respectively. No differences in hemorrhagic complications were observed across the groups. The in vitro model indicated that, compared with standard unsheathing technique, PFT resulted in improved wall apposition (device diameter, 75% larger) and cell size (mean area, 51% larger) at the cost of a mild degree of foreshortening (25% length reduction). CONCLUSIONS: The PFT is safe and leads to optimization of wall apposition and cell size/configuration, resulting in higher chances of first-pass reperfusion, lower number of passes, and better rates of complete reperfusion. PMID- 26374487 TI - Irving J. Selikoff MD, photographs. PMID- 26374486 TI - Melting of Pb Charge Glass and Simultaneous Pb-Cr Charge Transfer in PbCrO3 as the Origin of Volume Collapse. AB - A metal to insulator transition in integer or half integer charge systems can be regarded as crystallization of charges. The insulating state tends to have a glassy nature when randomness or geometrical frustration exists. We report that the charge glass state is realized in a perovskite compound PbCrO3, which has been known for almost 50 years, without any obvious inhomogeneity or triangular arrangement in the charge system. PbCrO3 has a valence state of Pb(2+)(0.5)Pb(4+)(0.5)Cr(3+)O3 with Pb(2+)-Pb(4+) correlation length of three lattice-spacings at ambient condition. A pressure induced melting of charge glass and simultaneous Pb-Cr charge transfer causes an insulator to metal transition and ~10% volume collapse. PMID- 26374485 TI - Ligand-dependent genomic function of glucocorticoid receptor in triple-negative breast cancer. AB - Glucocorticoids (GCs) have been widely used as coadjuvants in the treatment of solid tumours, but GC treatment may be associated with poor pharmacotherapeutic response or prognosis. The genomic action of GC in these tumours is largely unknown. Here we find that dexamethasone (Dex, a synthetic GC)-regulated genes in triple-negative breast cancer (TNBC) cells are associated with drug resistance. Importantly, these GC-regulated genes are aberrantly expressed in TNBC patients and are associated with unfavourable clinical outcomes. Interestingly, in TNBC cells, Compound A (CpdA, a selective GR modulator) only regulates a small number of genes not involved in carcinogenesis and therapy resistance. Mechanistic studies using a ChIP-exo approach reveal that Dex- but not CpdA-liganded glucocorticoid receptor (GR) binds to a single glucocorticoid response element (GRE), which drives the expression of pro-tumorigenic genes. Our data suggest that development of safe coadjuvant therapy should consider the distinct genomic function between Dex- and CpdA-liganded GR. PMID- 26374488 TI - The rise of a Titan: Irving J. Selikoff and his campaign for independent science. PMID- 26374489 TI - Commentary on pathologic diagnosis of asbestosis and critique of the 2010 Asbestosis Committee of the College of American Pathologists (CAP) and Pulmonary Pathology Society's (PPS) update on the diagnostic criteria for pathologic asbestosis. AB - We reviewed the 2010 Asbestosis Committee's update on the diagnostic criteria for pathologic asbestosis. We must respectfully disagree with many of the criteria set forth therein, especially for recognizing asbestosis at its earliest stages; with statements focusing on the number of asbestos bodies needed in order to make a pathologic diagnosis of asbestosis; and regarding the benefits and pitfalls of relying on fiber analysis for diagnostic purposes, especially where chrysotile asbestos is concerned, including the methodology used for fiber determination. This critique has become even more relevant with the 2014 Helsinki criteria publication, which adopted the 2010 CAP/PPS criteria. Based on our review of these newer criteria and our experience in this field, we find that the CAP-NIOSH 1982 criteria is still the most acceptable method for the pathologic diagnosis and grading of asbestosis, which can be described as pulmonary fibrosis caused by inhalation of asbestos fibers. PMID- 26374490 TI - Patterns of pneumoconiosis mortality in Kentucky: Analysis of death certificate data. AB - BACKGROUND: Mortality rates associated with total pneumoconiosis, including coal worker's pneumoconiosis (CWP), have remained elevated. METHODS: 2003-2013 pneumoconiosis mortality data obtained from National Center for Health Statistics and 2011-2013 Kentucky death certificates were analyzed. RESULTS: Total pneumoconiosis mortality rates showed significant linear decreases in West Virginia, Pennsylvania, Kentucky, and the U.S. from 2003 to 2013; Pennsylvania and Kentucky had comparable rates in 2003 but while Pennsylvania rates significantly decreased ~3.0 deaths/million annually, Kentucky rates decreased only 0.5/million annually. Kentucky and Pennsylvania CWP fatality rates were also comparable in 2003 but while Pennsylvania rates decreased 82% over the study period, Kentucky rates decreased only 26%. Kentucky pneumoconiosis deaths primarily occurred in white Appalachian males in-hospital. Diseases leading to pneumoconiosis death were largely respiratory and cardiovascular, with autopsies rarely performed. CONCLUSIONS: Coal worker environmental exposure protection should be enhanced and pneumoconiosis surveillance improvements, including enhanced management of comorbid conditions like COPD, should be considered. PMID- 26374491 TI - Balance of lifetime remaining to anticipated suffering behind. PMID- 26374492 TI - Evaluation of an intensified prevention program for 4th graders with increased caries risk using ICDAS. AB - BACKGROUND: In order to investigate correlations between specific parameters and dental caries, it is useful to record incipient and dentine lesions. AIM: The aim of this study was to evaluate the effect of a selective intensified preventive program (SIP) on oral health of fourth graders using ICDAS. DESIGN: A cohort study was performed. ICDAS and DMFT index were recorded. Prevention and social factors were collected with psychometric questionnaires. The test group and the control group were parallelized using sociodemographic variables. RESULTS: The participants in the fluoride varnish program in the test region showed a significantly lower caries experience than pupils in the control region. The bivariate analysis revealed that a migrant background had a negative impact on oral health whereas fissure sealants, use of fluoridated table salt, use of fluoride tablets, early start of toothbrushing and high social status exerted a positive influence on dental health. Stepwise backward logistic regression analysis confirmed that fissure sealants, a high social status and an early start of toothbrushing had a significant positive impact on dental health. CONCLUSION: The results of our study suggest that a SIP impedes the primary occurrence of incipient lesions and the transition from incipient to advanced lesions. PMID- 26374493 TI - Chemical composition, nutritional value and in vitro starch digestibility of roasted chickpeas. AB - BACKGROUND: Chickpea is considered a wholesome and nutritious food due to its nutritional properties and glycemic response. Such properties can be influenced by the thermal treatment used to cook this legume and produce a snack named leblebi. From the consumers' point of view, it is desirable to improve texture and palatability of the chickpea by the processing steps used to make leblebi. However, consumers are increasingly concerned with the nutritional value of snack foods. RESULTS: Nutritional components and digestibility properties of single and double heat-treated chickpea, single and double roasted leblebi and white leblebi were studied. High sodium, starch damage and soluble dietary fiber content were observed in white leblebi; while the other samples showed significantly (P < 0.05) higher insoluble dietary fiber content. Heat treatment and processing significantly (P < 0.05) altered the viscosity and starch properties of the samples. High resistant starch content (28.28% to 30.20%) and low estimated glycemic index (38.67 to 41.28) in heat-treated chickpeas and roasted leblebi were observed. CONCLUSION: The results indicate that heat-treated chickpea and roasted leblebi have good nutritional quality and low glycemic response. White leblebi had relatively high sodium content and glycemic response. (c) 2015 Society of Chemical Industry. PMID- 26374494 TI - Loss of membrane-bound lytic transglycosylases increases outer membrane permeability and beta-lactam sensitivity in Pseudomonas aeruginosa. AB - The opportunistic pathogen Pseudomonas aeruginosa is a leading cause of nosocomial infections. Its relatively impermeable outer membrane (OM) limits antibiotic entry, and a chromosomally encoded AmpC beta-lactamase inactivates beta-lactam antibiotics. AmpC expression is linked to peptidoglycan (PG) recycling, and soluble (sLT) or membrane-bound (mLT) lytic transglycosylases are responsible for generating the anhydromuropeptides that induce AmpC expression. Thus, inhibition of LT activity could reduce AmpC-mediated beta-lactam resistance in P. aeruginosa. Here, we characterized single and combination LT mutants. Strains lacking SltB1 or MltB had increased beta-lactam minimum inhibitory concentrations (MICs) compared to wild type, while only loss of Slt decreased MICs. An sltB1 mltB double mutant had elevated beta-lactam MICs compared to either the sltB1 or mltB single mutants (96 vs. 32 MUg/mL cefotaxime), without changes to AmpC levels. Time-kill assays with beta-lactams suggested that increased MIC correlated with a slower rate of autolysis in the sltB1 mltB mutant - an antisuicide phenotype. Strains lacking multiple mLTs were more sensitive to beta-lactams and up to 16-fold more sensitive to vancomycin, normally incapable of crossing the OM. Multi-mLT mutants were also sensitive to bile salts and osmotic stress, and were hyperbiofilm formers, all phenotypes consistent with cell envelope compromise. Complementation with genes encoding inactive forms of the enzymes - or alternatively, overexpression of Braun's lipoprotein - reversed the mutants' cell envelope damage phenotypes, suggesting that mLTs help to stabilize the OM. We conclude that P. aeruginosa mLTs contribute physically to cell envelope stability, and that Slt is the preferred target for future development of LT inhibitors that could synergize with beta-lactams. PMID- 26374496 TI - Improvement of wine aromatic quality using mixtures of lysozyme and dimethyl dicarbonate, with low SO2 concentration. AB - The use of sulphur dioxide (SO2) in the treatment of foodstuffs presents some problems as it could lead to pseudo-allergies in some people. The aim of this research work was to study the addition of different preservative mixtures and their influence on the concentration of volatile compounds and sensorial quality in wine. To do so, vinifications were carried out using Garnacha must to which lysozyme, dimethyl dicarbonate (DMDC) and mixtures of these with SO2 were added at different doses (25 and 50 mg l(-1)). The results were compared with a control sample to which only SO2 had been added (50 mg l(-1)). In general, mixtures of SO2 with lysozyme and DMDC favoured the formation of volatile compounds in the wines. Wines obtained from the mixtures of lysozyme and DMDC with 25 mg l(-1) of SO2 had better sensorial quality than the wines obtained with 50 mg l(-1) as the only preservative used. PMID- 26374495 TI - Formation of Polychlorinated Biphenyls on Secondary Copper Production Fly Ash: Mechanistic Aspects and Correlation to Other Persistent Organic Pollutants. AB - Emission of unintentionally formed polychlorinated biphenyls (PCBs) from industrial thermal processes is a global issue. Because the production and use of technical PCB mixtures has been banned, industrial thermal processes have become increasingly important sources of PCBs. Among these processes, secondary copper smelting is an important PCB source in China. In the present study, the potential for fly ash-mediated formation of PCBs in the secondary copper industry, and the mechanisms involved, were studied in laboratory thermochemical experiments. The total PCB concentrations were 37-70 times higher than the initial concentrations. Thermochemical reactions on the fly ash amplified the potential toxic equivalents of PCBs. The formation of PCBs over time and the effect of temperature were investigated. Based on analyses of PCB homologue profiles with different reaction conditions, a chlorination mechanism was proposed for forming PCBs in addition to a de novo synthesis mechanism. The chlorination pathway was supported by close correlations between each pair of adjacent homologue groups. Formation of PCBs and multiple persistent organic pollutants, including polychlorinated dibenzo-p dioxins, polychlorinated dibenzofurans and polychlorinated naphthalenes, occurred during the tests, indicating that these compounds may share similar formation mechanisms. PMID- 26374497 TI - Initial respiratory status in hyperleukocytic acute myeloid leukemia: prognostic significance and effect of leukapheresis. AB - This study investigated whether initial respiratory status in hyperleukocytic acute myeloid leukemia (AML), as defined by oxygen/ventilatory support, is (1) associated with early mortality and overall survival and (2) improved after leukapheresis. A retrospective chart review of 89 patients requiring leukapheresis was performed. White blood cell count (WBC) decreased from 153 (56 475) * 10(9)/L to 60 (17-259) * 10(9)/L after first leukapheresis (p < 0.01). Initial respiratory status was room air (n = 40), low (n = 31) or high flow oxygen therapy (n = 8) or mechanical ventilation (n = 10). As compared to admission, respiratory status significantly deteriorated after both first and second leukapheresis (p < 0.01) and was not different at day 5 for patients still alive (p = 0.131). Both day 28 mortality and overall survival were significantly affected by initial respiratory status (p < 0.01). Despite being effective in reducing WBC, leukapheresis did not improve respiratory status of hyperleukocytic AML patients, a factor strongly associated with survival. PMID- 26374498 TI - Asthma management during pregnancy: how long before we can all breathe a little easier? PMID- 26374499 TI - Parental perspectives on goals of care discussions with the healthcare team for their child with cancer. PMID- 26374500 TI - On the serial homology of the pectoral and pelvic girdles of tetrapods. AB - While fore- and hindlimbs are commonly assumed to be serially homologous, the serial homology of the pectoral and pelvic girdles is more ambiguous. We investigate the degree to which a common history, developmental program, and gene network are shared between the girdles relative to the rest of the appendicular skeleton. Paleontological data indicate that pectoral appendages arose millions of years before pelvic appendages. Recent embryological and genetic data suggest that the anatomical similarity between the fore- and hindlimbs arose through the sequential, derived deployment of similar developmental programs and gene networks, and is therefore not due to ancestral serial homology. Much less developmental work has however been published about the girdles. Here, we provide the first detailed review of the developmental programs and gene networks of the pectoral and pelvic girdles. Our review shows that, with respect to these programs and networks, there are fewer similarities between pelvic and pectoral girdles than there are between the limbs. The available data therefore support recent hypotheses that the anatomical similarities between the fore- and hindlimbs arose during the fin-to-limb transition through the derived co-option of similar developmental mechanisms, while the phylogenetically older pectoral and pelvic girdles have remained more distinct since their evolutionary origin. PMID- 26374501 TI - Age-driven modulation of tRNA-derived fragments in Drosophila and their potential targets. AB - BACKGROUND: Development of sequencing technologies and supporting computation enable discovery of small RNA molecules that previously escaped detection or were ignored due to low count numbers. While the focus in the analysis of small RNA libraries has been primarily on microRNAs (miRNAs), recent studies have reported findings of fragments of transfer RNAs (tRFs) across a range of organisms. RESULTS: Here we describe Drosophila melanogaster tRFs, which appear to have a number of structural and functional features similar to those of miRNAs but are less abundant. As is the case with miRNAs, (i) tRFs seem to have distinct isoforms preferentially originating from 5' or 3' end of a precursor molecule (in this case, tRNA), (ii) ends of tRFs appear to contain short "seed" sequences matching conserved regions across 12 Drosophila genomes, preferentially in 3' UTRs but also in introns and exons; (iii) tRFs display specific isoform loading into Ago1 and Ago2 and thus likely function in RISC complexes; (iii) levels of loading in Ago1 and Ago2 differ considerably; and (iv) both tRF expression and loading appear to be age-dependent, indicating potential regulatory changes from young to adult organisms. CONCLUSIONS: We found that Drosophila tRF reads mapped to both nuclear and mitochondrial tRNA genes for all 20 amino acids, while previous studies have usually reported fragments from only a few tRNAs. These tRFs show a number of similarities with miRNAs, including seed sequences. Based on complementarity with conserved Drosophila regions we identified such seed sequences and their possible targets with matches in the 3'UTR regions. Strikingly, the potential target genes of the most abundant tRFs show significant Gene Ontology enrichment in development and neuronal function. The latter suggests that involvement of tRFs in the RNA interfering pathway may play a role in brain activity or brain changes with age. PMID- 26374502 TI - Determinants of waterpipe use amongst adolescents in Northern Sweden: a survey of use pattern, risk perception, and environmental factors. AB - BACKGROUND: Determinants of waterpipe use in adolescents are believed to differ from those for other tobacco products, but there is a lack of studies of possible social, cultural, or psychological aspects of waterpipe use in this population. This study applied a socioecological model to explore waterpipe use, and its relationship to other tobacco use in Swedish adolescents. METHODS: A total of 106 adolescents who attended an urban high-school in northern Sweden responded to an anonymous questionnaire. Prevalence rates for waterpipe use were examined in relation to socio-demographics, peer pressure, sensation seeking behavior, harm perception, environmental factors, and depression. RESULTS: Thirty-three percent reported ever having smoked waterpipe (ever use), with 30% having done so during the last 30 days (current use). Among waterpipe ever users, 60% had ever smoked cigarettes in comparison to 32% of non-waterpipe smokers (95% confidence interval 1.4-7.9). The odds of having ever smoked waterpipe were three times higher among male high school seniors as well as students with lower grades. Waterpipe ever users had three times higher odds of having higher levels of sensation-seeking (95% confidence interval 1.2-9.5) and scored high on the depression scales (95% confidence interval 1.6-6.8) than non-users. The odds of waterpipe ever use were four times higher for those who perceived waterpipe products to have pleasant smell compared to cigarettes (95% confidence interval 1.7-9.8). Waterpipe ever users were twice as likely to have seen waterpipe use on television compared to non-users (95% confidence interval 1.1-5.7). The odds of having friends who smoked regularly was eight times higher for waterpipe ever users than non-users (95% confidence interval 2.1-31.2). CONCLUSION: The current study reports a high use of waterpipe in a select group of students in northern Sweden. The study adds the importance of looking at socioecological determinants of use, including peer pressure and exposure to media marketing, as well as mental health among users. PMID- 26374505 TI - Translation and validation of the Chinese version of the Current Opioid Misuse Measure (COMM) for patients with chronic pain in Mainland China. AB - BACKGROUND: Management of prescription opioids misuse and abuse problems among chronic pain patients has been increasingly important worldwide and little literature concerning prescription opioids can be found in mainland China so far. METHODS: The Current Opioid Misuse Measure (COMM) was translated into Chinese following Brislin's model of cross-culture translation and was completed by a convenience sample of 180 patients with chronic pain recruited from two major hospitals in Jinan, Shandong province. Data were analyzed using internal consistency, test-retest reliability, exploratory factor analysis and confirmatory factor analysis. RESULTS: The internal consistency coefficient for the total score of the COMM was 0.85 and item-total correlations of all items were above 0.20. Besides, the test-retest reliability was satisfactory with an ICC of 0.91 (95% CI = 0.65-0.98). Four principal components were extracted, accounting for 65.30% of the variance, and the factor loadings of all 17 items were above 0.40. CONCLUSIONS: The Chinese version of COMM showed satisfactory reliability and validity, and could be used as a screening tool to evaluate and monitor current aberrant drug-related behavior among Chinese patients with chronic pain. PMID- 26374506 TI - Photobacterium galatheae sp. nov., a bioactive bacterium isolated from a mussel in the Solomon Sea. AB - A novel, Gram-negative marine bacterium, S2753T, was isolated from a mussel of the Solomon Sea, Solomon Islands. Analysis of the 16S rRNA gene sequence and whole genome sequence data placed strain S2753T in the genus Photobacterium with the closest relative being Photobacterium halotolerans DSM 18316T (97.7 % 16S rRNA gene similarity). Strain S2753T was able to grow from 15 to 40 degrees C and in NaCl concentrations of 0.5 to 9 % (w/v). The predominant fatty acids were 16 : 1omega7c/16 : 1omega6c (27.9 %), 16 : 0 (22.1 %) and 18 : 1omega7c/8 : 1omega6c (21.4 %). The genomic DNA G+C mol content was 49.5 mol%. Based on the phylogenetic, chemotaxonomic and phenotypic differences, strain S2753T is considered to represent a novel species of the genus Photobacterium. Furthermore, whole genome sequence analysis comparing S2753T and type-strains of closely related species of the genus Photobacterium also demonstrated that the strain is genomically distinct enough to be considered a novel species. The name Photobacterium galatheae is proposed and the type-strain is S2753T( = LMG 28894T = DSM 100496T). PMID- 26374507 TI - Multiple sclerosis--a dynamic field with a need for excellent education. PMID- 26374508 TI - A basic overview of multiple sclerosis immunopathology. AB - Multiple sclerosis (MS) is a multi-component disease characterized by inflammation, neurodegeneration and failure of central nervous system (CNS) repair mechanisms. Immune dysregulation appears to originate with dendritic cells (antigen-presenting cells) which have an activated phenotype in individuals with MS. Dendritic cells migrate across the blood-brain barrier and induce differentiation of memory T cells into pro-inflammatory T helper 1 (Th1) and Th17 lymphocytes. In turn, induction of macrophage and microglial activation produces other pro-inflammatory cytokines and oxygen and nitric oxide radicals responsible for the demyelination and axonal loss. Other known mediators of MS pathology include CD8+ T cells and memory B cells within the CNS. Some pathological hallmarks of MS are early axonal degeneration and progressive decline of brain volume in patients with clinically isolated syndromes who progress to clinically definite MS. Many new options to interfere with the course of MS have become available in recent years. To limit inflammatory demyelinating processes and delay disease progression, intervention to control inflammation must begin as early as possible. Each distinct type of immunotherapy (immunomodulation, immunosuppression and immune-selective intervention - blockade type, sequestering type or depleting type) corresponds to a specific underlying immunopathology of MS. PMID- 26374509 TI - Overview of the management of relapsing-remitting multiple sclerosis and practical recommendations. AB - The initial phases of the clinical course of relapsing-remitting multiple sclerosis (MS) are characterized by a mainly inflammatory pathology which gives way to a largely neurodegenerative process as the disease evolves. As all currently available disease-modifying therapies aim to control inflammation, the window of opportunity for use is early in the disease course, specifically at the time of a clinically isolated syndrome suggestive of MS or in the early stages of relapsing-remitting MS. Approximately 30% of patients treated with first-line immunomodulators (interferon-beta or glatiramer acetate) show a suboptimal response during the first 1-2 years and require a switch to an alternative therapy. It is recommended not to wait too long to switch in order to prevent disease progression. Patients with a poor prognosis in particular may require a timely switch to a second-line agent. Regular monitoring of disease and therapy in patients with MS is essential. In the first year after diagnosis, clinical evaluations (neurological status, symptomatic assessment, patient well-being) should be performed at baseline, 3, 6 and 12 months, and then every 6 months thereafter. Brain magnetic resonance imaging (MRI) should be performed every 6 months in the first year of treatment, and at least once yearly thereafter. A spinal cord MRI should be performed once yearly in patients presenting spinal symptoms. PMID- 26374510 TI - Overview of magnetic resonance imaging for management of relapsing-remitting multiple sclerosis in everyday practice. AB - Although the value of magnetic resonance imaging (MRI) for diagnosis/differential diagnosis of patients with clinically isolated syndromes suggestive of multiple sclerosis (MS) is widely accepted, adoption of MRI into clinical practice to monitor disease evolution remains a work in progress. However, an accumulating body of evidence points to a central role for MRI in managing patients with relapsing-remitting MS along the disease continuum. Routine MRI surveillance provides insight into disease activity that is not evident clinically and this information, in turn, can be used to inform prognosis and guide treatment decisions. In Europe, practical guidelines have been developed to reduce the heterogeneity of imaging (both intracentre and intercentre) and improve the quality of MRI assessment and interpretation. Aimed at the general neurologist, this review explores some of the issues associated with MRI and examines evidence supporting its use for routine monitoring of MS patients in everyday practice. PMID- 26374511 TI - 'Hidden' factors influencing quality of life in patients with multiple sclerosis. AB - Traditional outcome measures for patients with multiple sclerosis (MS), whether in clinical trials or clinical practice, are currently in question. The combination of relapses, physical disability progression and magnetic resonance imaging (MRI) disease activity reflect only part of the impact that MS has on a patient's daily life. Quality of life (QoL) is considered by many to be the ideal outcome measure. Since it captures the patient's own perspective of well-being, QoL should be the primary focus when evaluating a patient and the main objective of MS management. Nevertheless, whilst numerous instruments to measure QoL in MS patients are available or proposed, there is no current consensus regarding which is the best tool to use and under what circumstances. QoL in patients with MS is determined by several factors beyond the more obvious; these include coping with the MS diagnosis, understanding the disease and the disease process, dealing with so-called 'hidden' symptoms such as fatigue, cognitive impairment and sexual disturbances, and managing the many associated personal challenges such as social isolation, family issues and working difficulties. Evidence is emerging that psychological interventions may be beneficial in MS patients although more research is required to confirm their utility. This article examines some factors that influence QoL in MS patients which may be overlooked in the general busyness of routine clinical practice. PMID- 26374512 TI - An overview of pregnancy-related issues in patients with multiple sclerosis. AB - Although pregnancy in women with multiple sclerosis (MS) is not generally considered high risk, there are some associated therapeutic challenges. The pregnancy-associated reduction in the relapse rate, especially in the third trimester, is followed by a sharp increase in the first few months postpartum. Nevertheless, retrospective evidence for pregnant women with and without MS followed for up to 10 years indicates that pregnancy has no perceptible effect on long-term disease course or disability progression. Likewise, MS has no apparent effects on the pregnancy course or fetal outcomes. All disease-modifying therapies (DMTs) have potential adverse effects on fertility and pregnancy outcomes, but the level of risk varies amongst agents. There is some support for continued use of interferon-beta and glatiramer acetate throughout pregnancy to reduce the risk of relapse. Use of DMTs during breastfeeding is best avoided if possible. Close evaluation of drug safety information is imperative when managing women with MS who are pregnant or wish to become pregnant. Decision-making should be a shared experience between patient and physician, and the approach must be individualized for each patient. PMID- 26374514 TI - Excessive sitting at work and at home: Correlates of occupational sitting and TV viewing time in working adults. AB - BACKGROUND: Recent evidence links sedentary behaviour (or too much sitting) with poorer health outcomes; many adults accumulate the majority of their daily sitting time through occupational sitting and TV viewing. To further the development and targeting of evidence-based strategies there is a need for identification of the factors associated with higher levels of these behaviours. This study examined socio-demographic and health-related correlates of occupational sitting and of combined high levels of occupational sitting/TV viewing time amongst working adults. METHODS: Participants were attendees of the third wave (2011/12) of the Australian Diabetes, Obesity and Lifestyle (AusDiab) study who worked full-time (>=35 h/week; n = 1,235; 38 % women; mean +/- SD age 53 +/- 7 years). Logistic and multinomial logistic regression analyses were conducted (separately for women and men) to assess cross-sectional associations of self-reported occupational sitting time (categorised as high/low based on the median) and also the combination of occupational sitting time/TV viewing time (high/low for each outcome), with a number of potential socio-demographic and health-related correlates. RESULTS: Higher levels of occupational sitting (>6 h/day) were associated with higher household income for both genders. Lower levels of occupational sitting were associated with being older (women only); and, for men only, having a blue collar occupation, having a technical/vocational educational attainment, and undertaking more leisure-time physical activity (LTPA). Attributes associated with high levels of both occupational sitting and TV viewing time included white collar occupation (men only), lower levels of LTPA (both genders), higher BMI (men), and higher energy consumption (women). CONCLUSIONS: Higher household income (both genders) and professional/managerial occupations (men only) were correlates of high occupational sitting time, relative to low occupational sitting time, while health-related factors (lower LTPA, higher BMI - men, and higher energy consumption - women) were associated with high levels of both occupational sitting and TV viewing time, relative to low occupational sitting and low TV viewing time. These findings suggest possible high-risk groups that may benefit from targeted interventions. Further research is needed on potentially modifiable environmental and social correlates of occupational sitting time, in order to inform workplace initiatives. PMID- 26374513 TI - Adoptive transfer of immune cells from glaucomatous mice provokes retinal ganglion cell loss in recipients. AB - INTRODUCTION: Several studies have indicated that autoimmune and neuroinflammatory processes contribute to the neurodegeneration of retinal ganglion cells in human glaucoma patients and in animal models. To test the involvement of cellular immune processes in the pathophysiology of retinal ganglion cell degeneration in vivo, we carried out adoptive transfer experiments from two independent genetic mouse models of glaucoma into normal recipient mice. RESULTS: Our findings indicate that transfer results in a progressive loss of retinal ganglion cells and their axons despite normal intraocular pressure in recipient mice. Signs of pan-retinal inflammation were not detected. Similar findings were obtained following transfer of isolated T-lymphocytes, but not after transfer of splenocytes from immune deficient glaucomatous mice. Transferred lymphocytes were detected integrated in the spleen and in the retinal ganglion cell layer of recipient animals, albeit at very low frequencies. Furthermore, we observed cell-cell interaction between transferred T-cells and recipient microglia along with focal microglial activation in recipient eyes. CONCLUSION: This study demonstrates that the pathophysiology of glaucomatous degeneration in the tested animal models includes T-cell mediated events that are capable of causing loss of healthy retinal ganglion cells. PMID- 26374517 TI - Climate change reduces nectar secretion in two common Mediterranean plants. AB - Global warming can lead to considerable impacts on natural plant communities, potentially inducing changes in plant physiology and the quantity and quality of floral rewards, especially nectar. Changes in nectar production can in turn strongly affect plant-pollinator interaction networks-pollinators may potentially benefit under moderate warming conditions, but suffer as resources reduce in availability as elevated temperatures become more extreme. Here, we studied the effect of elevated temperatures on nectar secretion of two Mediterranean Lamiaceae species-Ballota acetabulosa and Teucrium divaricatum. We measured nectar production (viz. volume per flower, sugar concentration per flower and sugar content per flower and per plant), number of open and empty flowers per plant, as well as biomass per flower under a range of temperatures selected ad hoc in a fully controlled climate chamber and under natural conditions outdoors. The average temperature in the climate chamber was increased every 3 days in 3 degrees C increments from 17.5 to 38.5 degrees C. Both study species showed a unimodal response of nectar production (volume per flower, sugar content per flower and per plant) to temperature. Optimal temperature for sugar content per flower was 25-26 degrees C for B. acetabulosa and 29-33 degrees C for T. divaricatum. According to our results, moderate climate warming predicted for the next few decades could benefit nectar secretion in T. divaricatum as long as the plants are not water stressed, but have a moderate negative effect on B. acetabulosa. Nevertheless, strong warming as predicted by climate change models for the end of the 21st century is expected to reduce nectar secretion in both species and can thus significantly reduce available resources for both wild bees and honeybees in Mediterranean systems. PMID- 26374515 TI - Variant of the clock circadian regulator (CLOCK) gene and related haplotypes are associated with the prevalence of type 2 diabetes in the Japanese population. AB - BACKGROUND: Circadian rhythm disruptions can cause various health disorders. The present study evaluated associations between single nucleotide polymorphisms in the core circadian gene clock circadian regulator (CLOCK) and the prevalence of type 2 diabetes (T2D) in the Japanese population. METHODS: Cross-sectional data were analyzed from 2485 subjects (1243 men, 1242 women; age 35-69 years) enrolled in the baseline surveys of the Japan Multi-Institutional Collaborative Cohort (J MICC) Study. Associations between three CLOCK gene polymorphisms (rs1801260, rs3736544, and rs4864548) and the prevalence of obesity (body mass index [BMI] >=25 kg/m(2) ), overweight (BMI >=23 kg/m(2) ), and T2D were evaluated by logistic regression analyses; haplotype analysis and stratified analyses for the prevalence of diabetes were also conducted. RESULTS: Compared with those who were homozygous for the respective major alleles, subjects with the rs1801260 minor allele C had a significantly higher odds ratio (1.5; 95% confidence interval 1.1 2.1) for the prevalence of diabetes after adjustment for potential confounding factors, including BMI. When stratified by overweight, the associations between rs1801260 and the prevalence of diabetes were marked and significant in non overweight subjects, but not in overweight subjects. The TGA (rs1801260-rs3736544 rs4864548) haplotype was associated with a lower prevalence of diabetes, whereas the CGG haplotype was associated with a higher prevalence of diabetes. CONCLUSIONS: Variant of the CLOCK gene and related haplotypes are associated with the prevalence of T2D in the Japanese population, in which obesity is less common, and the association between CLOCK gene variant at rs1801260 and the prevalence of diabetes is enhanced in normal-weight subjects. PMID- 26374519 TI - Programmed Cell death in Development and Tumors. PMID- 26374518 TI - A Patient-Specific Foot Model for the Estimate of Ankle Joint Forces in Patients with Juvenile Idiopathic Arthritis. AB - Juvenile idiopathic arthritis (JIA) is the leading cause of childhood disability from a musculoskeletal disorder. It generally affects large joints such as the knee and the ankle, often causing structural damage. Different factors contribute to the damage onset, including altered joint loading and other mechanical factors, associated with pain and inflammation. The prediction of patients' joint loading can hence be a valuable tool in understanding the disease mechanisms involved in structural damage progression. A number of lower-limb musculoskeletal models have been proposed to analyse the hip and knee joints, but juvenile models of the foot are still lacking. This paper presents a modelling pipeline that allows the creation of juvenile patient-specific models starting from lower limb kinematics and foot and ankle MRI data. This pipeline has been applied to data from three children with JIA and the importance of patient-specific parameters and modelling assumptions has been tested in a sensitivity analysis focused on the variation of the joint reaction forces. This analysis highlighted the criticality of patient-specific definition of the ankle joint axes and location of the Achilles tendon insertions. Patient-specific detection of the Tibialis Anterior, Tibialis Posterior, and Peroneus Longus origins and insertions were also shown to be important. PMID- 26374520 TI - Dying to survive - apoptosis, necroptosis, autophagy as supreme experiments of nature. AB - Guido Kroemer has made fundamental contributions to medical research through his pioneering work in the fields of cell death and cancer research. He is best known for the discovery that the permeabilization of mitochondrial membranes constitutes a decisive step in programmed cell death. Kroemer has explored the fine mechanisms of mitochondrial cell death control, the molecular pathways that explain the inhibition of cell death in cancer cells, upstream of or at the level of mitochondria, and the mechanisms that make cancer cell death immunogenic. Moreover, he discovered the AIF protein and clarified its biological role in apoptosis. His important contributions have been recognized with numerous awards. Kroemer currently serves on more than forty Editorial Boards and is a member of the European Molecular Biology Organization (EMBO), German Academy of Sciences, Austrian Academy of Sciences, European Academy of Sciences (EAS), European Academy of Sciences and Arts (EASA), and European Academy of Cancer Sciences (EACS). He is the President of the European Cell Death Organization (ECDO) and the Founding Director of the European Research Institute for Integrated Cellular Pathology (ERI-ICP). Kroemer is the most cited scientist worldwide in the field of cell death as well as in the area of mitochondrial research. PMID- 26374521 TI - What cell death does in development. AB - Cell death is prominent in gametogenesis and shapes and sculpts embryos. In non mammalian embryos one sees little or no cell death prior to the maternal-zygotic transition, but, in mammalian embryos, characteristic deaths of one or two cells occur at the end of compaction and are apparently necessary for the separation of the trophoblast from the inner cell mass. Considerable sculpting of the embryo occurs by cell deaths during organogenesis, and appropriate cell numbers, especially in the CNS and in the immune system, are generated by massive overproduction of cells and selection of a few, with death of the rest. The timing, identity, and genetic control of specific cells that die have been well documented in Caenorhabditis, but in other embryos the stochastic nature of the deaths limit our ability to do more than identify the regions in which cells will die. Complete disruption of the cell death machinery can be lethal, but many mutations of the regulatory machinery yield only modest or no phenotypes, indicating substantial redundancy and compensation of regulatory mechanisms. Most of the deaths are apoptotic and are identified by techniques used to recognize apoptosis, but techniques identifying lysosomes (whether in dying or involuting cells or in the phagocytes that invade the tissue) also reveal patterns of cell death. Aberrant cell deaths that produce known phenotypes are typically localized, indicating that the mechanism of activating a programmed death in a specific region, rather than the mechanism of death, is aberrant. These results lead us to conclude that we need to know much more about the conversations among cells that lead cells to commit suicide. PMID- 26374522 TI - Ecdysone-mediated programmed cell death in Drosophila. AB - During Drosophila development, the steroid hormone ecdysone plays a key role in the transition from embryo into larva and then into pupa. It is during larval pupal metamorphosis that extensive programmed cell death occurs to remove large obsolete larval tissues. During this transition, ecdysone pulses control the expression of specific transcription factors which drive the expression of key genes involved in cell death, thus spatially and temporally controlling programmed cell death. Ecdysone also controls cell death in specific larval and adult tissues. This review focuses on the current knowledge of ecdysone-mediated cell death in Drosophila. PMID- 26374523 TI - Apaf1 in embryonic development - shaping life by death, and more. AB - Apaf1 has been studied hitherto for its key role in regulating the formation of the apoptotic core machinery, the apoptosome, to induce programmed cell death. Apaf1 involvement in orchestrating this process during embryonic development has been widely documented and constitutes a breakthrough in developmental biology. In this review, we aim to highlight the origin of Apaf1 discoveries and how findings, mainly based on the analysis of knock-out mouse models, have led us to consider Apaf1 as a master player in fine-tuning apoptosis during embryonic development. Likewise, we also attempt to establish how Apaf1 function is locally time-dependent in regulating neurodevelopment and becomes dispensable during neuron maturation. We go on to discuss Apaf1's new functions which have been unveiled in recent years and which could revise or, at least, adjust the common view of Apaf1 having merely an apoptotic role. Hence, by presenting clear indications on the pro-survival roles of Apaf1, this review seeks to provide novel and more complex insights into Apaf1 involvement in nervous system development. PMID- 26374524 TI - Programmed cell death in mouse primordial germ cells. AB - In a number of mammalian species, the main events of development of the primordial germ cells (PGCs), the embryonic precursors of the oocytes and spermatozoa, were described during the early twentieth century. Actually, the concept of the origin of germ cells in extragonadal sites before the formation of the gonadal anlagen, was put forward for the human embryo around the first decade of the 1900s (for a review, see De Felici, 2013). PGC development is characterized by two major cellular processes, a movement from the wall of the yolk sac, where the germline is determined, to the gonadal anlagen and an increase in number due to active proliferation. As far as we know, the notion that programmed cell death (PCD) might physiologically occur in mammalian PGCs was for the first time put forward by us in 1993 in the case of the mouse. How we arrived to such a concept and the progress made up to now in the characterization of this process in our and other laboratories mainly in the mouse are the topics of the present review. PMID- 26374525 TI - Multifaceted programmed cell death in the mammalian fetal ovary. AB - From previous and more recent works reviewed in the present paper, it appears that mammalian fetal oocytes face several challenges to survive throughout the stages of meiotic prophase I up to the block at the diplotene/dictyate stage and the primordial follicle assembly. Depending on the period of development and experimental conditions, these oocytes can undergo different forms of programmed cell death (PCD) and cross-talking pathways. We hypothesize that they require the continuous support of growth factors to accomplish the activities required to overcome PCD during prophase I. An extraordinary level of DNA double strand break (DSB) tolerance characterizes oocytes during the first stages of meiotic prophase I. However, the activation of a p63/p53-and PCNA-dependent DNA damage checkpoint, plays a major role in eliminating defective oocytes when they reach the diplotene stage. Before oocytes are enclosed into a primordial follicle, the shortness of nutrients/growth factors might activate protective autophagy but this can turn into their death if starvation is prolonged. Actually, clarifying the relationships among growth factor signalling (mainly AKT cascade), apoptotic and autophagic proteins that seem to coexist in fetal oocytes, could be the key to understanding PCD in these cells. PMID- 26374526 TI - Interdigital tissue regression in the developing limb of vertebrates. AB - Here we have chosen the regression of the interdigital tissue which sculpts the digits from the hand/foot plate in tetrapod embryos to review the most relevant aspects concerning the regulation and biological significance of programmed cell death. We gather abundant information showing that the initiation of the degenerative process is the result of a complex interplay between the different signaling pathways which are also responsible for limb outgrowth and skeletal tissue differentiation, rather than being regulated by a specific signaling pathway. The model further shows that once the death response is triggered, several different routes of cell disruption, including caspase-dependent apoptosis, lysosomal-mediated cell death, and even a cell senescence process, are activated in the interdigits to ensure their elimination. Transcriptional and structural changes accompanying the degenerative process, and their posible contribution to the control of the death process, are also revised in detail. Finally we survey a number of issues still awaiting clarification, such as the functional implication of interdigital cell death as a source of signals acting on the surrounding tissues, as occurs in the so called "regenerative cell death". PMID- 26374527 TI - Development and programed cell death in the mammalian eye. AB - Programmed cell death (PCD) is a major mechanism for patterning of a variety of complex structures. Cells are initially organized into fairly loose patterns; then, selective death removes the cells between pattern elements to create the correct structures, as a sculptor removes some material to reveal the hidden image. The life or death of a cell is mostly affected by extracellular signals because the intracellular machinery responsible for PCD is constitutively expressed in most animal cells. The optic vesicle originates during gastrulation when the endoderm and mesoderm interact with the adjacent prospective head ectoderm to create a lens. To be formed correctly, the lens must have a precise spatial relationship with the retina. Ganglion cells are the first neurons to be differentiated in the retina. Vertical networks in the inner and outer retina are later interconnected when bipolar cells are formed and connections with ganglion cells are established. This sequential pattern of retinal circuit development is common across vertebrate species. During development of the retina, far more neurons are generated than are ultimately needed with almost one half of them undergoing PCD shortly before establishing meaningful contacts within their targets. However, apoptosis in other eye tissues is not a key event but rather a refinement. Thus, for the final development of the cornea, the control of keratocyte proliferation is more important than cell death events. The molecular mechanisms underlying apoptotic cell death have been conserved throughout evolution; however further investigations are needed to understand the key mechanisms of PCD in different tissues during development. PMID- 26374528 TI - Programmed cell death in the skin. AB - Differently from the other cells of the body, epidermal cells of the skin undergo a specific programmed cell death form named cornification. Many events take part to control this process, which has been described as a terminal differentiation program. Going from the innermost layer to the outermost, epidermal cells stop dividing, change their shape, acquire new cellular structures and strengthen their cytoskeleton. This is corroborated by the fact that during this physical transition they change their gene expression, reprogramming in some way their biochemical activity. The activation of critical enzymes, including proteases and transglutaminases is a fundamental cellular event. These enzymes are involved in building the supramolecular and cornified structures which confer resistance to the epidermis which carries out a vital function as a skin barrier, preserving the organism from various insults. Here we review current concepts about cornification and the mechanisms by which this process is preserved in species. PMID- 26374529 TI - Cell competition, apoptosis and tumour development. AB - The phenomenon of cell competition is an interactive process originally discovered in the imaginal discs of Drosophila; it is a developmental mechanism that identifies and eliminates cells that are weaker than their neighbours or have features that make them different or not well adapted to their surroundings. It appears to be an important homeostatic mechanism to contribute to the general fitness of developing tissues. Here we discuss some of the basic features of cell competition and then focus on results indicating that cell competition is responsible for the removal of malignant or aberrant cells that may appear during development, although in certain circumstances it can revert its role to promote tumour growth. We also consider several recent studies that indicate that cell competition also occurs in vertebrates where it performs similar functions. PMID- 26374530 TI - P63 in health and cancer. AB - TP63 is the most ancient member of the p53 gene family. The p53 family comprises three transcription factors (p53/p63/p73). They share a high degree of homology and similar domain structure. Yet, they can exist as truncated isoforms. Alternative promoters and splicing sites lead to the generation of several molecules. P53/p63/p73 are important to maintain cell homeostasis. P63 and p73 regulate many p53 target genes. This is due to their common structural features. Both proteins may compensate the loss of p53. This is a common event occurring in more than 50% of malignancies. Yet, p63 (or p73) has its own role. Studies from p63-null mice have shown the key role of p63 in embryo development. Several reports have supported the p63 role in epidermal development and in skin homeostasis. P63 involvement in heart development is currently being researched. Recent studies have found p63 to be "the guardian of human reproduction". In addition, p63 has an important, even controversial, role in cancer. Here, we provide a general overview of p63 regulation and activity. We discuss emerging concepts about its role in germ line protection, metabolism and cancer. PMID- 26374531 TI - Role of autophagy in the maintenance and function of cancer stem cells. AB - Recent advances in experimental technologies and cancer models have made possible to demonstrate that the tumor is a dynamic system comprising heterogeneous populations of cancer cells organized in a hierarchical fashion with cancer stem cells (CSCs) at the apex. CSCs are immature cells characterized by self-renewal property and long-term repopulation potential. CSCs have been causally linked to cancer initiation, propagation, spreading, recurrence and relapse as well as to resistance to anticancer therapy. A growing body of evidence suggests that the function and physiology of CSCs may be influenced by genetic/epigenetic factors and tumor environment. In this context, macroautophagy is a lysosomal degradative process (herein referred to as autophagy) critical for the adaptive response to stress and the preservation of cellular and tissue homeostasis in all eukaryotes that may have a crucial role of in the origin, maintenance and invasiveness of CSCs. The activation of the autophagic machinery is also considered as an adaptive response of CSCs to perturbation of tumor microenvironment, caused for instance by anticancer therapy. Nevertheless, compelling preclinical and clinical evidence on the cytoprotective role of autophagy for CSCs is still missing. Here, we summarize the results on the contribution of autophagy in CSCs and how it impacts tumorigenesis and tumor progression. We also discuss the therapeutical potential of the modulation of autophagy as a means to eradicate CSCs. PMID- 26374532 TI - AMBRA1-regulated autophagy in vertebrate development. AB - Autophagy is a catabolic process that mediates the lysosomal turn over of organelles and macromolecules, and is strongly activated in stress conditions to ensure cell survival. Autophagy core genes are highly conserved from yeast to mammals, with an increasing number of positive and negative regulators that have evolved in higher eukaryotes. Autophagy takes part in different stages of development, as revealed by alterations in cell proliferation, differentiation and survival during the embryogenesis of organisms carrying mutations in autophagy genes. These defects are ascribed to the ability of autophagy to provide elements for new synthesis or energy production in limiting conditions during embryogenesis, as well as to contribute to the profound cell remodeling that occurs during differentiation. However, many differences have been observed in the phenotypes of autophagy mutant organisms, indicating that these genes have acquired specific functions in particular tissues, which may reflect the ability of autophagy to crosstalk with the main developmental processes. In this review, we discuss the role of upstream regulators of autophagy in the development of different model systems, focusing, in particular, on AMBRA1 (autophagy/beclin-1 regulator-1) and its role in the central nervous system. PMID- 26374533 TI - Cell death in cancer therapy of lung adenocarcinoma. AB - Lung cancer is the main cause of all cancer-related deaths in the world, with lung adenocarcinoma (ADC) being the most common subtype of this fatal disease. Lung ADC is often diagnosed at advanced stages involving disseminated metastatic tumors. This is particularly important for the successful development of new cancer therapy approaches. The high resistance of lung ADC to conventional radio- and chemotherapies represents a major challenge to treatment effectiveness. Here we discuss recent progress in understanding the mechanisms of ADC's broad resistance to treatment and its possible therapeutic implications. A number of driving oncogenic alterations were identified in a subset of lung ADCs, making them suitable for targeted therapies directed towards specific cancer-associated molecular changes. In addition, we discuss the molecular aberrations common in lung ADC that are currently being exploited or are potentially important for targeted cancer therapy, as well as limitations of this type of therapy. Furthermore, we highlight possible treatment modalities that hold promise for overcoming resistance to targeted therapies as well as alternative treatment options such as immunotherapies that are potentially promising for improving the clinical outcome of lung ADC patients. PMID- 26374534 TI - Immunogenic cell death. AB - Currently, it is widely acknowledged that a proactive anticancer immunosurveillance mechanism takes part in the rejection of neoplastic lesions before they progress towards a benign or malignant tumour. However in cases of very aggressive neoplastic lesions consisting of cells with high mutational diversity, cancer cell variants might be formed that are capable of evading host defence systems against uncontrolled proliferation and anticancer immunosurveillance. This is mainly accomplished through the exhibition of low immunogenicity, which is a particularly important stumbling block in the revival of long-lasting as well as stable anticancer immunity. Recently, it has emerged emphatically that inciting a cancer cell death routine, associated with the activation of danger signalling pathways evoking emission of damage-associated molecular patterns (DAMPs), markedly increases the immunogenicity of dying cancer cells. This cell death pathway has been termed "immunogenic cell death" (ICD). In the present review we introduce this concept and discuss its characteristics in detail. We also discuss in detail the various molecular, immunological and operational determinants of ICD. PMID- 26374535 TI - Combinatorial cancer immunotherapy strategies with proapoptotic small-molecule IAP antagonists. AB - Members of the inhibitor of apoptosis (IAP) family control several critical aspects of innate immunity, cell death, and tumorigenesis. Small molecule antagonists that target specific IAP oncoproteins, primarily cIAP1 and cIAP2, but potentially also XIAP and Livin, modulate distinct immune signal transduction pathways that can lead to an increased sensitivity of tumors cells to cytokine mediated apoptosis. These antagonists are based on the structure of an endogenous cellular IAP inhibitor called Smac. Smac is normally sequestered within the mitochondria and is released into the cytoplasm upon cell death stimuli, thereby overcoming the anti-apoptotic action of the IAPs. The therapeutic usefulness of recombinant tumoricidal cytokines to treat cancer patients is principally limited due to their unacceptable adverse side effects. Therefore, investigators have sought to develop alternative regimens that do not rely on exogenously delivered death ligands. These approaches include the stimulation of the immune system with oncolytic virus-based agents or Toll-like receptor agonists in combination with Smac mimetics. Similarly, preclinical combination immunotherapy studies reveal that recombinant interferon synergizes with Smac mimetics to kill cancer. This strategy opens up new therapeutic avenues for anti-cancer therapy by modulating specific immune-mediated death pathways employing unique dual-pronged combinatorial approaches. PMID- 26374536 TI - Study of the gastrointestinal parasitic fauna of captive non-human primates (Macaca fascicularis). AB - The aim of this study was to examine helminths and protozoans in cynomolgus macaques (Macaca fascicularis) imported from registered breeding facilities in China and their relation to health risks for non-human primate handlers in biomedical research centers and in breeding facilities. Fresh fecal samples were collected from a total of 443 M. fascicularis and analyzed by copromicroscopical analysis, immunoenzymatic, or molecular assays. As to helminths, whose eggs were shed in 2.03% of the samples, Trichuris and Oesophagostomum were the only two taxa found, with low prevalence and low eggs per gram (EPG) values. Protozoans were more frequently detected (87.40%), with Entamoeba coli (85.19%) and Endolimax nana (79.26%) as the most prevalent species shed. Other parasites found by fecal smear examination were uninucleated-cyst-producing Entamoebas (78.52%), Iodamoeba butschlii (42.96%), and Chilomastix mesnili (24.44%), while cysts of Balantidium coli (22.2%) were only observed by sedimentation. No coproantigens of Giardia duodenalis, Cryptosporidium spp., and Entamoeba histolytica complex were detected. Blastocystis sp. infection was noticed in 87.63% of macaques by PCR. These cynomolgus monkeys were infected with many subtypes (ST1, ST2, ST3, ST5, and ST7), where the predominant Blastocystis sp. subtypes were ST2 (77.5%), followed by ST1 (63.5%). Data collected confirmed the presence of potentially zoonotic parasites and a high parasite diversity, suggesting the need for appropriate and sensitive techniques to adequately control them and related health risks for handlers of non-human primates in biomedical research centers and in breeding facilities. PMID- 26374537 TI - Cooling water of power plant creates "hot spots" for tropical fishes and parasites. AB - Thermally altered water bodies can function as "hot spots" where non-native species are establishing self-sustaining populations beyond their tropical and subtropical native regions. Whereas many tropical fish species have been found in these habitats, the introduction of non-native parasites often remains undetected. Here, n = 77 convict cichlids (Amatitlania nigrofasciata) were sampled by electro-fishing at two sites from a thermally altered stream in Germany and examined for parasite fauna and feeding ecology. Stomach content analysis suggests an opportunistic feeding strategy of A. nigrofasciata: while plant material dominated the diet at the warm water inlet (~30 degrees C), relative contributions of insects, plants, and crustaceans were balanced 3 km downstream (~27 degrees C). The most abundant non-native parasite species was the tropical nematode Camallanus cotti with P = 11.90 % and P = 80.00 % at the inlet and further downstream, respectively. Additionally, nematode larvae of Anguillicoloides crassus and one specimen of the subtropical species Bothriocephalus acheilognathi were isolated. A. nigrofasciata was also highly infected with the native parasite Acanthocephalus anguillae, which could be linked to high numbers of the parasite's intermediate host Asellus aquaticus. The aim of this study was to highlight the risk and consequences of the release and establishment of ornamental fish species for the introduction and spread of non indigenous metazoan parasites using the convict cichlid as a model species. Furthermore, the spread of non-native parasites into adjacent fish communities needs to be addressed in the future as first evidence of Camallanus cotti in native fish species was also found. PMID- 26374538 TI - Viruses in close associations with free-living amoebae. AB - As both groups of organisms, free-living amoebae (FLA) and viruses, can be found in aquatic environments side by side, it appears obvious that there are multiple interactions with respect to host-endocytobiont relationships. Several relationships between viruses and protozoan hosts are described and it was the discovery of the so called "giant viruses," associated with amoebae, which gave another dimension to these interactions. Mimiviruses, Pandoraviruses and Pithoviruses are examples for interesting viral endocytobionts within FLA. In the Mimivirus viral factories, viral DNA undergoes replication and transcription, and the DNA is prepared to be packed in procapsids. Theses Mimivirus factories can be considered as efficient "production lines" where, at any given moment, all stages of viral generation including membrane biogenesis, capsid assembly and genome encapsidation, are occurring concomitantly. There are some hints that similar replication factories are involved as well during the Pandoravirus development. Some scientists favour the assumption that the giant viruses have received many of their genes from their hosts or from sympatric occurring endocytobionts via lateral gene transfer. This hypothesis would mean that this type of transfer has been an important process in the evolution of genomes in the context of the intracellular parasitic or endocytobiotic lifestyle. In turn, that would migitate against hypothesizing development of a new branch in the tree of life. Based on the described scenarios to explain the presence of genes related to translation, it is also possible that earlier ancestors of today's DNA viruses were involved in the origin of eukaryotes. That possibly could in turn support the idea that cellular organisms could have evolved from viruses with growing autarkic properties. In future we expect the discovery of further (giant) viruses within free-living amoebae and other protozoa through genomic, transcriptomic and proteomic analyses. PMID- 26374539 TI - Parasitation of sea trout (Salmo trutta trutta L.) from the spawning ground and German coastal waters off Mecklenburg-Western Pomerania, Baltic Sea. AB - A total of 52 sea trouts, Salmo trutta trutta, were studied for parasites, originating from German freshwater streams and coastal waters of the Baltic Sea. While 35 specimens were caught mainly close to the shoreline in the Baltic Sea, 17 were sampled during their spawning migration in Warnow River and other neighboring rivers in Mecklenburg-Western Pomerania. A total of 12 different metazoan parasite species were found in sea trout originating from the Baltic Sea, including five digeneans, two cestodes, three nematodes, and two acanthocephalans. Marine and freshwater species were found. In the migratory trout, seven different parasite species were recorded (one digenean, two cestodes, one nematode, and one acanthocephalan), demonstrating lower parasite diversity and load during the spawning migration compared with the fish from the Baltic Sea. The anisakid nematodes Anisakis simplex (sensu stricto), Contraceacum rudolphii, and Hysterothylacium aduncum were identified by molecular analyses of the ITS-1, 5.8S, ITS-2, and flanking sequences of the rDNA. Together with the digenean Derogenes varicus, Hemiurus communis and H. luehei, and the cestode Diphyllobothrium dendriticum seven new host records for sea trout from the German part of the Baltic Sea are made. PMID- 26374540 TI - Preferential adsorption of pentachlorophenol from chlorophenols-containing wastewater using N-doped ordered mesoporous carbon. AB - Preferential removal of pentachlorophenol (PCP) from chlorophenols-containing wastewater has been attracted more attentions in wastewater treatment, since it is one of the most toxic pollutants. The adsorbent of N-doped ordered mesoporous carbon (M-OMC) with high BET surface area of 1901 m(2)/g, large pore volume of 1.64 cm(3)/g and uniform pore size of 3.45 nm has been successfully synthesized via evaporation-induced self-assembly (EISA) method. The effects of solution pH, pore structure of adsorbent and their surface chemical properties on PCP adsorption by M-OMC were investigated in comparison with ordered mesoporous carbon (OMC), and much higher PCP adsorption capacities of M-OMC were obtained. The significantly preferential adsorption of PCP was achieved in the treatment of tri-component wastewater including PCP, p-chlorophenol (CP) and 2.4.6 trichlorophenol (TCP), and its adsorption process well fitted the pseudo-second order kinetics model and the Langmuir isotherm. The initial sorption rate of PCP was 103.5 MUmol/(g/min), which was 2.97 times of TCP. It may be attributed to the intensification of pi-pi interaction between PCP and M-OMC with the nitrogen functional groups. Therefore, M-OMC is promising for removal of PCP in the adsorption pretreatment of chlorophenols-containing wastewater. PMID- 26374541 TI - Optimisation of dispersion parameters of Gaussian plume model for CO2 dispersion. AB - The carbon capture and storage (CCS) and enhanced oil recovery (EOR) projects entail the possibility of accidental release of carbon dioxide (CO2) into the atmosphere. To quantify the spread of CO2 following such release, the 'Gaussian' dispersion model is often used to estimate the resulting CO2 concentration levels in the surroundings. The Gaussian model enables quick estimates of the concentration levels. However, the traditionally recommended values of the 'dispersion parameters' in the Gaussian model may not be directly applicable to CO2 dispersion. This paper presents an optimisation technique to obtain the dispersion parameters in order to achieve a quick estimation of CO2 concentration levels in the atmosphere following CO2 blowouts. The optimised dispersion parameters enable the Gaussian model to produce quick estimates of CO2 concentration levels, precluding the necessity to set up and run much more complicated models. Computational fluid dynamics (CFD) models were employed to produce reference CO2 dispersion profiles in various atmospheric stability classes (ASC), different 'source strengths' and degrees of ground roughness. The performance of the CFD models was validated against the 'Kit Fox' field measurements, involving dispersion over a flat horizontal terrain, both with low and high roughness regions. An optimisation model employing a genetic algorithm (GA) to determine the best dispersion parameters in the Gaussian plume model was set up. Optimum values of the dispersion parameters for different ASCs that can be used in the Gaussian plume model for predicting CO2 dispersion were obtained. PMID- 26374542 TI - Danio rerio as a model in aquatic toxicology and sediment research. PMID- 26374543 TI - Heavy metal accumulation in lizards living near a phosphate treatment plant: possible transfer of contaminants from aquatic to terrestrial food webs. AB - We investigated the accumulation of heavy metals in Bosk's fringe-toed lizards (Acanthodactylus boskianus) living in Gabes region (southeastern Tunisia), in relation to habitat, diet, and distance from the Gabes-Ghannouche factory complex of phosphate treatment. More specifically, we compared the concentrations of cadmium, lead, and zinc in the stomach contents and samples of the liver, kidney, and tail from lizards living in four sites corresponding to different combinations of habitat (coastal dunes vs backshore) and distance from the factory complex (<500 vs 20 km). Examination of stomach contents showed that lizards living on the coastal dunes mainly feed on littoral amphipods, while those living in the backshore feed exclusively on terrestrial invertebrates. The concentrations of heavy metals in lizard tissues were overall positively correlated with those in the preys they ingested. Moreover, there was a general tendency towards increased concentrations of cadmium, lead, and zinc in the samples from lizards living on coastal dunes compared to those from the other sites, although some differences still lacked statistical significance. These results suggest that the highest contamination of lizards living on coastal dunes was probably related to the ingestion of contaminated amphipods. Thus, amphipods and Bosk's fringe-toed lizards seem to provide an important link between the marine and terrestrial food webs, with higher concentrations appearing to accumulate from materials released into the sea rather than the terrestrial environment. With regard to metal distribution among tissues, our results were overall in agreement with previous findings in other reptiles. In particular, cadmium was most concentrated in the liver samples, stressing once more the role of the liver as a storage organ of Cd. Moreover, high concentrations of the three assessed metals were found in the kidney samples, showing the role of the kidney as an active site of heavy metal accumulation. PMID- 26374544 TI - Excess sludge and herbaceous plant co-digestion for volatile fatty acids generation improved by protein and cellulose conversion enhancement. AB - Volatile fatty acids (VFA), the substrate for the bio-methane yield, can be generated from excess sludge or herbaceous plant waste during the anaerobic fermentation process. However, due to the high protein content and the low carbon to-nitrogen (C/N) ratio of excess sludge, the nutrient utilization of excess sludge to generate VFA and bio-methane usually becomes inefficient and uneconomical. In this study, the laboratory findings showed that both the organic conversion and VFA generation from the mixture of excess sludge and herbaceous plant waste (e.g., the tall fescue was used as model), could be significantly enhanced, especially when the C/N ratio was adjusted to 20/1. In order to get more VFA and bio-methane generation, the effects of different thermal pretreatment strategies on the excess sludge and tall fescue co-fermentation were investigated. The study of thermal pretreatment revealed that the maximal VFA generation (585.2 g COD/kg of total solids (TS)) from the mixture of sludge and tall fescue by thermal pretreatment at 100 degrees C was almost 9.9 and 4.1 times higher than un-pretreated sole sludge and tall fescue, respectively. Then the mechanism of enhanced VFA generation from the mixture by thermal pretreatment was investigated. It was observed that pretreating the mixture of excess sludge and tall fescue at 100 degrees C caused the greatest hydrolysis and acidification. The produced VFA was applied to generate the bio-methane, and it was showed that the bio-methane produced from the thermal-pretreated (100 degrees C) mixture was almost 9.6 and 4.9 times as high as un-pretreated sole sludge and tall fescue, respectively. In addition, the detection of enzyme activities showed that the main enzymes related to cellulose, hemicelluloses, lignin degradation, and acid forming were more active when VFA was produced from the thermal-pretreated (100 degrees C) mixture than other cases. Class Bacteroidia, class beta-Proteobateria, alpha-Proteobateria, and phylum Firmicutes of the reactor with 100 degrees C pretreated mixture were more active than that of the reactor with un-pretreated sludge. PMID- 26374545 TI - A comparison of methane emissions following rice paddies conversion to crab-fish farming wetlands in southeast China. AB - Rice paddies and aquaculture wetlands are typical agricultural wetlands that constitute one of the important sources of atmospheric methane (CH4). Traditional transplanted rice paddies have been experiencing conversion to pond aquaculture wetlands for pursuing higher economic benefits over the past decades in southeast China. A parallel field experiment was carried out to compare CH4 emissions from a transplanted rice paddy and its converted crab-fish farming wetland in southeast China. Over the rice-growing season, CH4 fluxes averaged 1.86 mg m(-2) h(-1) from rice paddies, and 1.14 and 0.50 mg m(-2) h(-1) for the treatments with or without aquatic vegetation present in the crab-fish farming wetlands, respectively. When averaged across the treatments, seasonal CH4 emissions from crab-fish framing wetlands were 52% lower than those from rice paddies. The CH4 fluxes were negatively related to water dissolved oxygen (DO) concentration but positively related to soil/sediment dissolved organic carbon (DOC) content in crab-fish farming wetlands. Dependence of CH4 fluxes on DO or DOC was intensified by the aquatic vegetation presence. By extrapolating the present CH4 emission rate with the current rice paddy-converted aquaculture cultivation area, the seasonal CH4 emissions from inland aquaculture wetlands during the critical farming stage (20 June to 18 October) were estimated to be 33.6 Gg ha(-1) in southeast China in 2012. Rice paddies conversion to crab-fish farming wetlands might have reduced CH4 emissions by 22-54% in mainland China. Results of this study suggest that the conversion of transplanted rice paddies to crab-fish aquaculture wetlands for higher economic benefits would also lead to a lower ecosystem CH4 release rate. PMID- 26374546 TI - Water deficit and aluminum interactive effects on generation of reactive oxygen species and responses of antioxidative enzymes in the seedlings of two rice cultivars differing in stress tolerance. AB - Aluminum (Al) is a major constraint to crop productivity in acid soils, whereas water deficit severely limits crop production in arid and semi-arid regions of the world. The objective of the present study was to examine the effects of both stresses, Al excess and water deficit, individually and in combination on the production of the reactive oxygen species (ROS) superoxide anion (O2(-)), hydrogen peroxide (H2O2), hydroxyl radical, and lipid peroxidation and the activity of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and guaiacol peroxidase (GPX) in the seedlings of two rice (Oryza sativa L.) cvs. Malviya-36 (sensitive to water deficit and Al) and Vandana (tolerant to water deficit and Al). When 15-day grown seedlings were exposed to water deficit (created with 15% polyethylene glycol, PEG-6000) or Al (1 mM AlCl3) treatment or both treatments together for 24-72 h, the lengths and fresh weights of root/shoot declined in the seedlings of the sensitive cultivar, whereas in the tolerant seedlings, either little or insignificant decline in these parameters was observed due to the treatments. Biochemical determinations and histochemical studies revealed that under a similar level of water deficit, Al, or combined treatment, seedlings of sensitive cultivar showed a higher level of production of O2(-), H2O2, hydroxyl radical, and lipid peroxides compared to the tolerant seedlings. Seedlings of tolerant cultivars, both in roots and shoots, had constitutively higher activity levels of antioxidative enzymes SOD, CAT, and GPX and showed a greater increase in activity under water deficit or Al treatment alone or in combination compared to the similarly treated seedlings of sensitive cultivar. Our results suggest that a lower constitutive level of ROS and a high antioxidative enzyme capacity are associated with tolerance to both water deficit and Al excess in rice seedlings. PMID- 26374547 TI - Modelling benzo[a]pyrene in air and vegetation for different land uses and assessment of increased health risk in the Iberian Peninsula. AB - The ability of the modelling system WRF + CHIMERE implemented with high spatial and temporal resolution over the Iberian Peninsula (IP) to represent the levels of benzo[a]pyrene (BaP) in air and vegetation was tested in areas where different land uses are observed. Biomonitoring data available on the levels of polycyclic aromatic hydrocarbons (PAHs) in pine needles from the IP were used to estimate the atmospheric concentrations of BaP and, at the same time, fuelled the comparison of the vegetation representations given by the model. A total of 70 sites were sampled, including urban, industrial, rural and remote locations, which revealed different performances of the method for air and vegetation concentrations of BaP. The validation of this chemistry transport model (CTM) was complemented with the data available from the European Monitoring and Evaluation Programme (EMEP) air sampling network. This, in association with a quantitative risk assessment (QRA) method, allowed the estimation of the increased risk of lung cancer due to exposure to BaPs in the IP for three target values set by the European Union. PMID- 26374548 TI - Non-invasive diagnosis of acute rejection in renal transplant patients using mass spectrometry of urine samples - a multicentre phase 3 diagnostic accuracy study. AB - BACKGROUND: Reliable and timely detection of acute rejection in renal transplant patients is important to preserve the allograft function and to prevent premature allograft failure. The current gold standard for the rejection diagnosis is an allograft biopsy which is usually performed upon an unexplained decline in allograft function. Because of the invasiveness of the biopsy, non-invasive tests have been suggested to diagnose acute rejection including mass spectrometry analysis of urine samples. DESIGN AND METHODS: The aim of this study is to examine the diagnostic accuracy of mass spectrometry analysis in urine for the diagnosis of acute rejections using the biopsy as gold-standard. The study is an ongoing prospective, single-arm, multicentre, phase 3 diagnostic accuracy study. It started in October 2011 and will be concluded in December 2015. Patient within the first year after transplantation who are scheduled for a biopsy to clarify unexplained impairment of the allograft are consecutively recruited into the study. The overall sample size (n = 600) was calculated to demonstrate a sensitivity of 83 % and a specificity of 70 % for a one-sided type one error of 2.5 % and a power of 80 % per hypothesis. Biopsy evaluation and mass spectrometry analysis of urine samples (obtained immediately before biopsy) are performed independently by different readers without knowledge from the respective other assessment. The follow-up observation period is 6 months. For the primary analysis, the lower limits of the two-sided 95 % Wald confidence intervals for sensitivity and specificity will be compared with the pre-specified thresholds (83 % for sensitivity and 70 % for specificity). In secondary analyses the predictive values, the diagnostic measures in subgroups, and the clinical course will be assessed. DISCUSSION: Previous phase 2 diagnostic accuracy studies (in small selected study populations) provided sufficient evidence to suggest mass spectrometry on urine samples as a promising approach to detect acute rejections. This study determines the diagnostic performance of the test in the routine setting of post-transplant patient care, compared to the biopsy-based rejection diagnosis. The next step would be a randomized trial to compare the two diagnostic strategies (including the urine test or not) in relation to patient relevant endpoints. TRIAL REGISTRATION: NCT01315067 ; March 14, 2011. PMID- 26374550 TI - Inhibition of Peripheral TNF-alpha and Downregulation of Microglial Activation by Alpha-Lipoic Acid and Etanercept Protect Rat Brain Against Ischemic Stroke. AB - Ischemic stroke, caused by obstruction of blood flow to the brain, would initiate microglia activation which contributes to neuronal damage. Therefore, inhibition of microglia-mediated neuroinflammation could be a therapeutic strategy for ischemic stroke. This study was aimed to elucidate the anti-inflammatory effects of alpha-lipoic acid and etanercept given either singly or in combination in rats subjected to middle cerebral artery occlusion. Both alpha-lipoic acid and etanercept markedly reduced cerebral infarct, blood-brain barrier disruption, and neurological motor deficits with the former drug being more effective with the dosage used. Furthermore, when used in combination, the reduction was more substantial. Remarkably, a greater diminution in the serum levels of tumor necrosis factor-alpha as well as the brain levels of microglial activation (e.g., microgliosis, amoeboid microglia, and microglial overexpression of tumor necrosis factor-alpha) was observed with the combined drug treatment as compared to the drugs given separately. We conclude that inhibition of peripheral tumor necrosis factor-alpha as well as downregulation of brain microglial activation by alpha lipoic acid or etanercept protect rat brain against ischemic stroke. Moreover, when both drugs were used in combination, the stroke recovery was promoted more extensively. PMID- 26374549 TI - Astrocytes Surviving Severe Stress Can Still Protect Neighboring Neurons from Proteotoxic Injury. AB - Astrocytes are one of the major cell types to combat cellular stress and protect neighboring neurons from injury. In order to fulfill this important role, astrocytes must sense and respond to toxic stimuli, perhaps including stimuli that are severely stressful and kill some of the astrocytes. The present study demonstrates that primary astrocytes that managed to survive severe proteotoxic stress were protected against subsequent challenges. These findings suggest that the phenomenon of preconditioning or tolerance can be extended from mild to severe stress for this cell type. Astrocytic stress adaptation lasted at least 96 h, the longest interval tested. Heat shock protein 70 (Hsp70) was raised in stressed astrocytes, but inhibition of neither Hsp70 nor Hsp32 activity abolished their resistance against a second proteotoxic challenge. Only inhibition of glutathione synthesis abolished astrocytic stress adaptation, consistent with our previous report. Primary neurons were plated upon previously stressed astrocytes, and the cocultures were then exposed to another proteotoxic challenge. Severely stressed astrocytes were still able to protect neighboring neurons against this injury, and the protection was unexpectedly independent of glutathione synthesis. Stressed astrocytes were even able to protect neurons after simultaneous application of proteasome and Hsp70 inhibitors, which otherwise elicited synergistic, severe loss of neurons when applied together. Astrocyte-induced neuroprotection against proteotoxicity was not elicited with astrocyte conditioned media, suggesting that physical cell-to-cell contacts may be essential. These findings suggest that astrocytes may adapt to severe stress so that they can continue to protect neighboring cell types from profound injury. PMID- 26374551 TI - Activation of mTOR signaling mediates the increased expression of AChE in high glucose condition: in vitro and in vivo evidences. AB - Acetylcholinesterase (AChE) is impaired in brain of diabetic animals, which may be one of the reasons for diabetes-associated cognitive decline. However, the mechanism is still unknown. The present study was designed to investigate whether the increased expression of AChE in central neurons under high glucose (HG) condition was due to activation of mammalian target of rapamycin (mTOR) signaling. It was found that more production of reactive oxygen species, and higher levels of phospho-Akt, phospho-mTOR, phospho-p70S6K, and AChE were detected in HT-22 cells in HG group than normal glucose group after culture for 24 h, which were all attenuated by an antioxidant N-acetyl-L-cysteine. A PI3K inhibitor LY294002 significantly decreased the levels of phospho-Akt, phospho mTOR, phospho-p70S6K, and AChE protein expression in HG-cultured HT-22 cells, and an mTOR inhibitor rapamycin markedly reduced the levels of phospho-mTOR, phospho p70S6K, and AChE expression. Furthermore, compared with normal rats, diabetic rats showed remarkable increases in levels of AChE activity and expression, malondialdehyde, phospho-mTOR, phospho-p70S6K, and a significant decrease in total superoxide dismutase activity in both hippocampus and cerebral cortex. However, much lower levels of phospho-mTOR, phospho-p70S6K, and AChE expression occurred in both brain regions of diabetic rats treated with rapamycin when compared with untreated ones. These results indicated that mTOR signaling was activated through the activation of PI3K/Akt pathway mediated by oxidative stress in HG-cultured HT-22 cells and diabetic rat brains, which contributed to the elevated protein expression of AChE in central neurons under the condition of HG. PMID- 26374553 TI - Efficacy and safety of ifosfamide in combination with carboplatin and etoposide in small cell lung cancer. AB - PURPOSE: Ifosfamide, a potent alkylating agent, is rarely incorporated into small cell lung cancer (SCLC) treatment. The aim of this study was to assess the efficacy and safety of ifosfamide in combination with carboplatin and etoposide (ICE) in previously untreated patients with SCLC. METHODS: From January 2002 to January 2014, we consecutively enrolled 69 patients with SCLC who were treated with ICE as initial chemotherapy at Kangbuk Samsung Hospital. The modified ICE regimen consists of ifosfamide 1200 mg/m(2)/day on days 1, 2, and 3 with mesna, etoposide 80 mg/m(2)/day on days 1, 2, and 3, and carboplatin AUC 6 on day 1. Treatment was repeated every 3 weeks and continued for up to nine cycles. Response assessments were performed every three cycles with computed tomography. RESULTS: Among 69 patients with SCLC, the median age was 69 years (range 51-88 years). Sixteen (23 %) patients had limited disease (LD), and 53 (77 %) had extensive disease (ED). The overall response rate was 73 %. Stable disease rate was 20 %. The median overall survival was 11.3 months [95 % confidence interval (CI) 8.9-14.1] in the overall population, 20.6 months (95 % CI 14.2-21.2) for LD and 9.1 months (95 % CI 7.8-11.6) for ED. The median number of administered cycles was 6 (range 1-9). Grade >=3 hematological toxicities included neutropenia (34 %), anemia (59 %), and thrombocytopenia (31 %). Grade >=3 non-hematological toxicities included peripheral neuropathy in 2 %. CONCLUSION: In chemonaive patients with SCLC, modified ICE is well tolerated and shows favorable efficacy. PMID- 26374552 TI - Dissecting the Role of Anti-ganglioside Antibodies in Guillain-Barre Syndrome: an Animal Model Approach. AB - Guillain-Barre syndrome (GBS) is an autoimmune polyneuropathy disease affecting the peripheral nervous system (PNS). Most of the GBS patients experienced neurological symptoms such as paresthesia, weakness, pain, and areflexia. There are also combinations of non-neurological symptoms which include upper respiratory tract infection and diarrhea. One of the major causes of GBS is due largely to the autoantibodies against gangliosides located on the peripheral nerves. Gangliosides are sialic acid-bearing glycosphingolipids consisting of a ceramide lipid anchor with one or more sialic acids attached to a neutral sugar backbone. Molecular mimicry between the outer components of oligosaccharide of gangliosides on nerve membrane and lipo-oligosaccharide of microbes is thought to trigger the autoimmunity. Intra-peritoneal implantation of monoclonal ganglioside antibodies secreting hybridoma into animals induced peripheral neuropathy. Recent studies demonstrated that injection of synthesized anti-ganglioside antibodies raised by hybridoma cells into mice initiates immune response against peripheral nerves, and eventually failure in peripheral nerve regeneration. Accumulating evidences indicate that the conjugation of anti-ganglioside monoclonal antibodies to activating FcgammaRIII present on the circulating macrophages inhibits axonal regeneration. The activation of RhoA signaling pathways is also involved in neurite outgrowth inhibition. However, the link between these two molecular events remains unresolved and requires further investigation. Development of anti ganglioside antagonists can serve as targeted therapy for the treatment of GBS and will open a new approach of drug development with maximum efficacy and specificity. PMID- 26374554 TI - Maternal and perinatal outcomes associated with a trial of labour after previous caesarean section in sub-Saharan countries. AB - OBJECTIVE: To assess the risks of uterine rupture, maternal and perinatal outcomes associated with a trial of labour (TOL) after one previous caesarean were compared with having an elective repeated caesarean section (ERCS) without labour in low-resource settings. DESIGN: A prospective 4-year observational study. SETTING: Senegal and Mali. SAMPLE: A cohort of 9712 women with one previous caesarean delivery. METHODS: Maternal and perinatal outcomes were compared between 8083 women who underwent a TOL and 1629 women who had an ERCS. Perinatal and maternal outcomes were then stratified according to the presence or absence of risk factors associated with vaginal birth after caesarean section. These outcomes were adjusted on maternal, perinatal and institutional characteristics. MAIN OUTCOME MEASURES: The risks of uterine rupture, maternal complication and perinatal mortality associated with TOL after one previous caesarean as compared with ERCS, RESULTS: The risks of hospital-based maternal complication [adjusted odds ratio (OR) 1.52; 95% CI 1.09-2.13; P = 0.013] and perinatal mortality (adjusted OR 4.53; 95% CI 2.30-9.92; P < 0.001) were significantly higher in women with a TOL compared with women who had an ERCS. However, when restricted to low-risk women, these differences were not significant (adjusted OR 0.90, 95% CI 0.55-1.46, P = 0.68, and adjusted OR 1.13; 95% CI 0.75-1.86; P = 0.53, for each outcome, respectively). Uterine rupture occurred in 25 (0.64%) of 3885 low-risk women compared with 70 (1.66%) of 4198 women with unfavourable risk factors. CONCLUSION: Low-risk women have no increased risk of maternal complications or perinatal mortality compared with women with one or more unfavourable factors. TWEETABLE ABSTRACT: Low-risk women have a lower risk of maternal complications or perinatal mortality compared with high-risk women. PMID- 26374555 TI - Minimally invasive perventricular device closure of doubly committed sub-arterial ventricular septal defects: single center long-term follow-up results. AB - BACKGROUND: To evaluate the long-term safety and efficacy of using perventricular device closure in treating selected patient with doubly committed sub-arterial ventricular septal defect (VSD) METHODS: During July 2007 and April 2011, 86 patients with doubly committed subarterial VSD who met the inclusion criteria were enrolled in this study. Perventricular closure was attempted using a unique design eccentric device under the guidance of transesophageal echocardiography. Complications such as residual shunt, arrhythmia, valve regurgitation were all recorded in postoperative period and during follow-up. Multiple logistic regression analysis was performed to study risk factors for procedure failure and complications. RESULT: Perventricular device closure was successfully done in 75 patients (87.2 %) with mean age 7.0 +/- 7.0 years old, VSD size 4.8 +/- 1.5 mm and device size 6.7 +/- 1.7 mm. Complete closure rate was achieved in 94.7 % at discharge and 96 % during follow-up. No severe complications such as device embolism, significant arrhythmia, left ventricular outflow tract obstruction as well as obvious valve regurgitation were noted during follow-up (Mean 4.5 +/- 1.5 years). Procedure induced trivial-mild grade aortic valve regurgitation (AR) was noted in 16 (21.3 %) patients at discharge while 8 of them resolved during follow up. Multivariable analysis revealed that procedure-induced AR was associated device diameter to patients' weight (OR=12.3 95 % CI 1.5- 99.2). Perventricular device closure was failed in 11 patients, preoperative aortic valve prolapse was the major risk factor for failure of the procedure (OR=65 95 % CI 7.5- 564.1). CONCLUSION: Perventricular closure of doubly committed subarterial VSDs appears to be a safe and effective minimally invasive treatment option in selected patients with good long-term outcomes. CLINICAL TRIAL REGISTRATION: Unique Identifier: ChiCTR-TNC-00000203 . PMID- 26374556 TI - Evaluation of immune cell markers in tumor tissue treated with radioimmunotherapy in an immunocompetent rat colon carcinoma model. AB - BACKGROUND: Immune cells within the tumor can act either to promote growth or rejection of tumor cells. The aim of the present study was to evaluate immune cell markers (number and localization) within the tumor before and during rejection due to radioimmunotherapy, to determine whether there is a change in markers related to rejection and/or tolerance of the tumor cells. METHODS: Thirty immunocompetent rats were inoculated with syngeneic rat colon carcinoma cells and 13-14 days later 21 of these rats were treated with 400 MBq/kg of (177)Lu-DOTA BR96 monoclonal antibodies. The treated animals were sacrificed and dissected 1, 2, 3, 4, 6, and 8 days post-injection in groups of three animals per day (6 animals on day 8); while the nine untreated animals were sacrificed and dissected on day 0. Paraffin sections were used for immunohistochemical staining of CD2, CD3, CD8alpha, CD68, and CD163 antigens. Positive cells were counted within: vital tumor cell areas, necrotic areas, granulation tissue surrounding and between the tumor cell areas. The change in the number of positive cells over time in tumors treated with radioimmunotherapy in the same location was evaluated with linear regression models. The number of positive cells in various locations and the number of various antigen-positive cells within the same location were also evaluated over time using box plots. RESULTS: There were a higher number of cells expressing immune cell markers in granulation tissue compared with vital tumor cell areas. Cells expressing markers decreased during radioimmunotherapy, and T-cell markers decreased more than macrophage markers in tumors treated with radioimmunotherapy. The expression of CD8alpha was higher than that of the other T-cell markers evaluated (CD3 and CD2), which could be explained by the additional expression of CD8alpha by natural killer (NK) cells and a subset of dendritic cells (DCs). The expression of CD68 (all macrophages, DCs, and neutrophils) tended to be higher than that of CD163 (pro-tumor macrophages). CONCLUSIONS: In this model, we demonstrated a higher number of positive cells for immune cell markers related to augmenting the immune rejection than immune tolerance of tumor cells in tumors and a decrease in markers during radioimmunotherapy. PMID- 26374557 TI - Immune Therapy in Pancreatic Cancer: Now and the Future? AB - Pancreatic cancer continues to be the most lethal malignancy with rising incidence. Traditional chemotherapy remains the standard treatment for advanced pancreatic cancer. Regimens like FOLFIRINOX (5-FU, leucovorin, irinotecan, and oxaliplatin) or gemcitabine and nab-paclitaxel have been used to palliate symptoms and prolong survival. Immune therapy is changing the current treatment paradigm for malignancy, especially with the recent development of antibodies that can modulate immune checkpoint pathways. Immunotherapy to treat pancreatic cancer is a promising approach due to its low toxicity and potential for creating life- long immune response. Multiple large phase III trials using simple vaccination strategies have failed to modulate the immune response in pancreatic cancer. However novel strategies with whole cell vaccines using hyperacute rejections (Algenpantucel- L) immunotherapy demonstrated 62% and 86% 12-month disease free survival and overall survival in resected pancreatic cancer patients. Combination of whole cell vaccine GVAX and mesothelin-secreting vaccine CRS-207 demonstrated an overall survival benefit in metastatic refractory pancreatic cancer patients. In the paper, we review the recently published and ongoing clinical trials using immune based treatment for pancreatic cancer. PMID- 26374558 TI - Optical Diagnosis of Head and Neck Cancers. AB - Head and neck cancer is one of the most common malignancies. Currently, it has a poor prognosis and significant mortality as the majority of malignancies present in later stages. Early diagnosis affords early intervention and the best chance of cure. However, the current gold standard for diagnosis largely depends on histopathology via an invasive procedure, tissue biopsy. The processing of biopsy material also inevitably leads to diagnostic delay and the possibility of taking an unrepresentative sample. Recently, there has been significantly increasing interest in the use of spectroscopy (e.g., fluorescence, elastic scattering, and Raman spectroscopy) and other optical systems to provide an early, real-time, non invasive, and in situ diagnosis. Such diagnosis is based on the fact that the optical spectrum derived from any tissue reveals information about the histological and biochemical characteristics of that tissue. These optical systems have not only a role in cancer detection but also in treatment through guided biopsy, surgical margin assessment, and the monitoring of therapeutic drugs. However, our literature search is limited only to clinical diagnosis and only to the clinical trials published within recent 15 years (in 2000-2014). In this review, we will discuss and summarize the progress and new findings from recent clinical trials using these optical systems in the diagnosis of head and neck cancer. PMID- 26374559 TI - Clinical Trials of Poly(ADP-Ribose) Polymerase Inhibitors for Cancer Therapy: A Review. AB - Poly(ADP-Ribose) Polymerase (PARP) is a family of enzymes involved in DNA repair, genome stability, cellular energy metabolism and cell division. Inhibition of PARP-1, the well characterized member of this family, has been explored as a strategy for enhancing anti-cancer activity of existing drugs and for developing new drugs. Recently unique enzymatic properties and biological functions of PARP 2 and PARP-3 have been discovered, further expanding the utility of PARP as a target for cancer pharmacotherapy. We compare and contrast the structural and enzymatic properties of these three members of the PARP family. Interactions of these enzymes with proteins specific to different DNA repair pathways are summarized. Further, we evaluate progress on development of PARP inhibitors as anticancer agents. Results of Phase I and Phase II clinical trials of seven PARP inhibitors, used alone or in combination with known anticancer agents are reviewed highlighting common observations regarding the maximum tolerable dose, adverse reactions profile, PARP inhibition and anticancer effects. While further clinical studies are warranted, based on current data, Olaparib (Ola), Veliparib (Veli) and Rucaparib (Ruca) offer considerable potential. Prolonged exposure to Ola and Veli leads to resistant cancer cells, primarily through restoration of the HR pathway, overexpression of the P-glycoprotein efflux pump or modulation of PARP expression. Some resistant cancer cells continue to respond to platinum based drugs, encouraging further development of PARP inhibitors for cancer treatment. Future course of this research, specifically focusing on use of PARP inhibition as a strategy for personalized cancer therapy, is discussed. PMID- 26374560 TI - Response from Yu Xiang to "Comment on The complete nucleotide sequence and genome organization of pea streak virus (genus Carlavirus)". PMID- 26374561 TI - Response from Ralf Dietzgen to "Comment on The complete nucleotide sequence and genome organization of pea streak virus (genus Carlavirus)". PMID- 26374562 TI - New cytotoxic spectinabilin derivative from ant-associated Streptomyces sp. 1H GS5. PMID- 26374564 TI - Use of fuzzy chromatography mass spectrometric (FCMS) fingerprinting and chemometric analysis for differentiation of whole-grain and refined wheat (T. aestivum) flour. AB - A fuzzy chromatography mass spectrometric (FCMS) fingerprinting method combined with chemometric analysis has been established for rapid discrimination of whole grain flour (WF) from refined wheat flour (RF). Bran, germ, endosperm, and WF from three local cultivars or purchased from a grocery store were studied. The state of refinement (whole vs. refined) of wheat flour was differentiated successfully by use of principal-components analysis (PCA) and soft independent modeling of class analogy (SIMCA), despite potential confounding introduced by wheat class (red vs. white; hard vs. soft) or resources (different brands). Twelve discriminatory variables were putatively identified. Among these, dihexoside, trihexoside, apigenin glycosides, and citric acid had the highest peak intensity for germ. Variable line plots indicated phospholipids were more abundant in endosperm. Samples of RF and WF from three cultivars (Hard Red, Hard White, and Soft White) were physically mixed to furnish 20, 40, 60, and 80 % WF of each cultivar. SIMCA was able to discriminate between 100 %, 80 %, 60 %, 40 %, and 20 % WF and 100 % RF. Partial least-squares (PLS) regression was used for prediction of RF-to-WF ratios in the mixed samples. When PLS models were used the relative prediction errors for RF-to-WF ratios were less than 6 %. Graphical Abstract Workflow of targeting discriminatory compounds by use of FCMS and chemometric analysis. PMID- 26374563 TI - Streptanoate, a new anticancer butanoate from Streptomyces sp. DC3. PMID- 26374565 TI - Novel workflow for combining Raman spectroscopy and MALDI-MSI for tissue based studies. AB - Molecular heterogeneity of cancer is a major obstacle in tumor diagnosis and treatment. To deal with this heterogeneity, a multidisciplinary combination of different analysis techniques is of urgent need because a combination enables the creation of a multimodal image of a tumor. Here, we develop a computational workflow in order to combine matrix-assisted laser desorption/ionization mass spectrometric (MALDI-MS) imaging and Raman microspectroscopic imaging for tissue based studies. The computational workflow can be used to confirm a spectral histopathology (SHP) based on one technique with another technique. In this contribution, we confirmed a Raman spectroscopic based SHP with MALDI-imaging. Owing to this combination, we could demonstrate, for a larynx carcinoma sample, that tissue types and different metabolic states could be extracted from the Raman spectra. Further investigations with the help of MALDI spectra yield a better characterization of variable epithelial differentiation and a better understanding of ongoing dysplastic alterations. PMID- 26374566 TI - Measurement of serum aldosterone in picomolar level by LC-MS/MS using charge tagged technique. AB - Aldosterone is a mineralocorticoid steroid hormone, the measurement of which in the clinical laboratory is principally performed for the investigation of primary hyperaldosteronism. Primary hyperaldosteronism is a specifically treatable and potentially curable form of hypertension, which typically presents as drug resistant hypertension and, in up to 37% of cases, hypokalemia. Accurate measurement of aldosterone concentration is essential for correct diagnosis. The serum concentrations of aldosterone are in the picomolar range and therefore sensitive aldosterone assays are required. With the advancement in instrumentation of LC-MS/MS, the picomolar range of aldosterone can be easily measured by the newer models, but for those with a less sensitive instrument, special technique for sample preparation to enhance assay sensitivity is required. This work described the use of charge-tagging for the picomolar measurement of serum aldosterone in a less sensitive LC-MS/MS instrument. The assay was linear up to 3000 pmol/L with lower limit of quantitation at 80 pmol/L. The mean relative recovery was 96.5% with a range of 89.3-101.6% for aqueous calibrators and the mean relative recovery was 94.8% with a range of 87.5-101.4% for serum calibrators. Intra-assay CVs range from 8.2% to 11.3%, and inter-assay CVs ranged from 8.5% to 13.5% at concentration range from 229 to 1720 pmol/L. The LC-MS/MS method compared well (y = 1.04x + 8.97) with the in-use radioimmunoassay method. There was no significant difference found (p = 0.7135) between results determined by LC-MS/MS and radioimmunoassay method. PMID- 26374567 TI - Upregulation of des-gamma-carboxy-prothrombin after portal vein embolization in a cirrhotic patient with hepatocellular carcinoma. AB - A 73-year-old female with hepatocellular carcinoma (HCC) received percutaneous transhepatic portal vein embolization (PTPE) before extensive right lobe hepatectomy. Serum levels of des-gamma-carboxy-prothrombin (DCP) were increased and remained at a high level until hepatectomy. Immunohistochemical examination revealed that an increased expression of DCP was demonstrated not only in HCC tissues, but also in the non-cancerous liver of the right lobe, where portal blood flow was blocked off as a result of PTPE. The serum level of DCP is known to be greatly increased in patients with HCC accompanied by portal vein invasion. We speculate that this increased DCP level is caused by both increased DCP production in HCC tissue and the surrounding non-cancerous liver, where portal flow is blocked off as a result of portal invasion by HCC. PMID- 26374568 TI - Health-system-based interventions to improve care in pediatric and adolescent type 1 diabetes. AB - Despite significant advances in pharmacology and technology, glycemic targets are difficult to achieve for patients with type 1 diabetes (T1D) and management remains burdensome for patients and their families. Quality improvement (QI) science offers a methodology to identify an aim, evaluate complex contributors to the goal, and test potential interventions to achieve outcomes of interest. Day to-day management of diabetes is often an iterative process but interventions exist at all care levels: individual patient and family, clinic, and larger population and health system. This article reviews current literature and proposes novel QI interventions for enhancing health outcomes, with attention to essential determinants or drivers of improved glycemic control and patient experience for pediatric T1D in the context of the Chronic Care Model. In-depth consideration of key drivers of successful T1D care, including self-management and integration of technology, are explored, and examples of larger health systems with improved outcomes, including Learning Health Systems are highlighted. PMID- 26374569 TI - Adipose tissue inflammation in the pathogenesis of type 2 diabetes. AB - At least 2.8 million people die each year as a result of being overweight or obese, and the biggest burden being obesity-related diseases. Overweight and obesity account for a major proportion of type 2 diabetes (T2D) cases. Obesity is associated with inflammation in adipose tissue, namely an infiltration and expansion of macrophages, which produce inflammatory cytokines that interfere with insulin signaling, and a loss of protective cells that promote adipose homeostasis. Thus, it is now clear that inflammation is an underlying cause or contributor to T2D as well as many other obesity-induced diseases, including atherosclerosis and cancer. Inflammatory pathways contribute to impaired glucose handling by adipocytes, hepatocytes, and muscle cells and interfere with insulin production and insulin signaling. This review highlights the roles of the different immune populations in lean adipose tissue and their importance in tissue homeostasis to keep inflammation at bay. We also discuss the changes that occur in these immune cells during the development of obesity, which has detrimental effects on the health of adipose tissue, and local and systemic insulin resistance. PMID- 26374570 TI - Is there a relationship between oral health and diabetic neuropathy? AB - Diabetic neuropathy is the most common microvascular complication of diabetes mellitus with high morbidity and mortality, and low quality of life. It has a broad spectrum of clinical forms, although distal symmetrical polyneuropathy is the most prevalent. Several oral complications including burning mouth syndrome, dry mouth, and impairment of the senses taste and smell are less-known manifestations of diabetic neuropathy and often overlooked. Periodontitis, tooth loss, and temporomandibular joint dysfunction may be also present in these patients and are equally debilitating. Periodontitis was declared the sixth complication of diabetes in 1993 and may contribute to poor glucose control. Hence, periodontitis and diabetes mutually and adversely affect each other. This review summarizes the available body of scientific literature that discusses oral manifestations in patients with diabetic neuropathy and identifies important areas where more research is needed. PMID- 26374572 TI - Photodegradation of clothianidin under simulated California rice field conditions. AB - BACKGROUND: Photodegradation can be a major route of dissipation for pesticides applied to shallow rice field water, leading to diminished persistence and reducing the risk of offsite transport. The objective of this study was to characterize the aqueous-phase photodegradation of clothianidin under simulated California rice field conditions. RESULTS: Photodegradation of clothianidin was characterized in deionized, Sacramento River and rice field water samples. Pseudo first-order rate constants and DT50 values in rice field water (mean k = 0.0158 min(-1) ; mean DT50 = 18.0 equivalent days) were significantly slower than in deionized water (k = 0.0167 min(-1) ; DT50 = 14.7 equivalent days) and river water (k = 0.0146 min(-1) ; DT50 = 16.6 equivalent days) samples. Quantum yield phic values demonstrate that approximately 1 and 0.5% of the light energy absorbed results in photochemical transformation in pure and field water respectively. Concentrations of the photodegradation product thiazolymethylurea in aqueous photolysis samples were determined using liquid chromatography-tandem mass spectrometry and accounted for <=17% in deionized water and <=8% in natural water. CONCLUSION: Photodegradation rates of clothianidin in flooded rice fields will be controlled by turbidity and light attenuation. Aqueous-phase photodegradation may reduce the risk of offsite transport of clothianidin from flooded rice fields (via drainage) and mitigate exposure to non-target organisms. (c) 2015 Society of Chemical Industry. PMID- 26374571 TI - Diabetes-related dysfunction of the small intestine and the colon: focus on motility. AB - In contrast to gastric dysfunction, diabetes-related functional impairments of the small and large intestine have been studied less intensively. The gastrointestinal tract accomplishes several functions, such as mixing and propulsion of luminal content, absorption and secretion of ions, water, and nutrients, defense against pathogens, and elimination of waste products. Diverse functions of the gut are regulated by complex interactions among its functional elements, including gut microbiota. The network-forming tissues, the enteric nervous system) and the interstitial cells of Cajal, are definitely impaired in diabetic patients, and their loss of function is closely related to the symptoms in diabetes, but changes of other elements could also play a role in the development of diabetes mellitus-related motility disorders. The development of our understanding over the recent years of the diabetes-induced dysfunctions in the small and large intestine are reviewed in this article. PMID- 26374573 TI - Missed lesions in endoscopic ultrasound. PMID- 26374574 TI - Endoscopic ultrasound guided vascular access and therapy (with videos). AB - The continued need to develop minimally invasive alternatives to surgical and radiologic interventions has driven the development of endoscopic ultrasound (EUS)-guided treatments. EUS has now stepped into the therapeutic arena. EUS provides the unique advantage of both real-time imaging and access to structures within and adjacent to the gastrointestinal (GI) tract. Hence, EUS-guided therapeutic techniques continue to evolve in several directions enabling a variety of minimally invasive therapies for pancreatic and biliary pathologies. Furthermore, the close proximity of the GI tract to vascular structures in the mediastinum and abdomen permits EUS-guided vascular access and therapy. Studies have demonstrated several EUS-guided vascular interventions by using standard endoscopic accessories and available tools from the interventional radiology armamentarium. This article provides an overview of the literature including clinical and nonclinical studies for the management of nonvariceal and variceal GI bleeding, formation of intrahepatic portosystemic shunts (IPSS), and EUS guided cardiac access and therapy. PMID- 26374576 TI - Endobronchial ultrasound-guided transbronchial needle aspiration of pulmonary artery tumors: A systematic review (with video). AB - Convex probe endobronchial ultrasound (CP-EBUS) was originally introduced as a diagnostic and staging tool for lung cancer and subsequently utilized for diagnosis of other malignant and benign mediastinal diseases such as melanoma, lymphoma, and sarcoidosis. More recently, CP-EBUS has been successfully used for the visualization and diagnosis of pulmonary emboli and other vascular lesions including primary and metastatic pulmonary artery (PA) tumors. In this review, we will underline the role of EBUS-guided transbronchial needle aspiration (EBUS TBNA) for the diagnosis of pulmonary arterial tumors such as sarcomas and tumor emboli. We will concisely discuss the clinical applications of EBUS-TBNA and the types of pulmonary arterial tumors and their different diagnostic modalities. We searched the Cochrane Library and PubMed from 2004 to 2014 to provide the most comprehensive review. Only 10 cases of EBUS-TBNA for intravascular lesions were identified in the literature. Although many cases of EBUS and EUS-guided transvascular tumor biopsies were described in the literature, there were no reported cases of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for intravascular tumor biopsies. Except for one paper, all cases were published as case reports. PMID- 26374577 TI - Imaging of the pancreatic duct by linear endoscopic ultrasound. AB - The current gold standard investigation for anatomic exploration of the pancreatic duct (PD) is endoscopic retrograde cholangiopancreatography. Magnetic resonance cholangiopancreatography is a noninvasive method for exploration of the PD. A comprehensive evaluation of the course of PD and its branches has not been described by endoscopic ultrasound (EUS). In this article, we describe the techniques of imaging of PD using linear EUS. PMID- 26374575 TI - Endoscopic ultrasound: Elastographic lymph node evaluation. AB - Different imaging techniques can bring different information which will contribute to the final diagnosis and further management of the patients. Even from the time of Hippocrates, palpation has been used in order to detect and characterize a body mass. The so-called virtual palpation has now become a reality due to elastography, which is a recently developed technique. Elastography has already been proving its added value as a complementary imaging method, helpful to better characterize and differentiate between benign and malignant masses. The current applications of elastography in lymph nodes (LNs) assessment by endoscopic ultrasonography will be further discussed in this paper, with a review of the literature and future perspectives. PMID- 26374578 TI - Factors determining recurrence of fluid collections following migration of intended long term transmural stents in patients with walled off pancreatic necrosis and disconnected pancreatic duct syndrome. AB - BACKGROUND AND OBJECTIVES: Long-term indwelling transmural stents in patients with walled off pancreatic necrosis (WOPN) and disconnected pancreatic duct syndrome (DPDS) decreases risk of recurrence of pancreatic fluid collection (PFC). However, stents can spontaneously migrate causing recurrence of PFC in some patients whereas some patients may have asymptomatic migration of stents. We aim to retrospectively evaluate profile of patients with recurrent PFC following migration of transmural stents in patients with WOPN and DPDS and compare it with patients who had asymptomatic migration of stents. PATIENTS AND METHODS: Records of consecutive patients who underwent endoscopic transmural drainage of WOPN over last 4 years were analyzed and patients with DPDS identified. RESULTS: Thirty five patients (29 M; mean age 37.0 +/- 7.6 years) were followed-up for mean of 28.2 +/- 14.0 months (range: 6-50 months). Eight patients (22.8%) had spontaneous migration of stents. It led to recurrence of PFC in three patients, whereas in five patients it was asymptomatic. The patients with recurrent PFC had early stent migration (2, 4, and 5 months respectively) whereas patients with asymptomatic migration had their stents migrating >6 months of resolution. Patients with recurrent PFC had duct disruption in pancreatic head (100% vs. 20%), and low frequency of diabetes (nil vs. 40%), steatorrhea (nil vs. 20%) as well as pancreatic atrophy (nil vs. 80%). CONCLUSION: Early migration of stents, ductal disruption in pancreatic head as well as absence of diabetes, steatorrhea, and pancreatic atrophy seem to increase risk of recurrent PFC following migration of transmural stents in patients with DPDS. PMID- 26374580 TI - Prevalence of extra-pancreatic cysts in patients with cystic pancreatic lesions detected by endoscopic ultrasound. AB - BACKGROUND AND OBJECTIVES: Extra-pancreatic cysts (EPCs) are incidentally found in patients with pancreatic cystic lesions (PCLs). The aim of this study is to find the prevalence of concurrent EPC in patients with PCLs, investigate associations with neoplastic lesions, and compare the prevalence of EPC to a control population. MATERIALS AND METHODS: A retrospective study of patients who underwent endoscopic ultrasound (EUS) over a 3-year period. The study group consisted of patients with PCLs. The control group included equal number of matched (age and sex) patients who had undergone EUS for reasons other than evaluation of PCLs. All patients had undergone computed tomography (CT) that was reviewed for EPCs. RESULTS: A total of 191 patients were found to have PCLs. One patient with Von Hippel-Lindau (VHL) disease was excluded. Majority of the patients were female (60%); most PCLs were solitary (68.9%), unilocular (56.8%), predominantly located in the head of the pancreas (37.4%); and mean PCL diameter was 28.12 +/- 18.4mm. EUS-guided fine-needle aspiration (FNA) was performed in 171 (90%) patients with 73 (42.7%) PCLs demonstrating cysts with benign epithelial cells, 37 (21.6%) mucinous cysts, 18 (10.5%) mucinous adenocarcinomas, 11 (6.4%) neuroendocrine tumors, nine intraductal papillary mucinous cystic neoplasms (IPMNs), six pseudocysts, five serous cyst adenomas (SCAs), and five with inadequate sampling. An EPC was observed in 97 of 190 (51.18%) patients with PCLs and in 67 of 190 (35.3%) controls (P < 0.001). The distribution of EPCs in PCL patients and controls (n = 190) were 32.1% vs. 15.8% (P < 0.001) for liver cysts, 30.0% vs. 20.5% (P = 0.04) for renal cysts, and 3.7% vs. 1.6% (P = 0.34) for cysts in other organs. Mean liver cyst diameter (15.6 mm vs. 10.1 mm, P = 0.23) and renal cyst diameter (20.4 mm vs. 20.1 mm, P = 0.95) were not statistically different in PCL patients compared to controls. Multivariate analysis demonstrated that among patients with PCLs, EPCs increased with age (mean age 69.6 vs. 62.4 years, P <= 0.001, odds ratio (OR) 1.06, 95% confidence interval (CI) 1.03, 1.09), and male gender was associated with higher chance of finding renal cysts (OR 2.17, P = 0.021, 95% CI 1.13, 4.19). There was no association between FNA result and prevalence or type of EPC. CONCLUSION: The prevalence of EPCs in patients with PCLs was significantly higher than in a matched control group. Among patients with PCLs, a liver cyst is the most common EPC. Increasing age is associated with higher prevalence of EPCs. PMID- 26374579 TI - Endoscopic drainage of pancreatic fluid collections using a fully covered expandable metal stent with antimigratory fins. AB - BACKGROUND AND OBJECTIVES: Endoscopic drainage is the first consideration in treating pancreatic fluid collections (PFCs). Recent data suggests it may be useful in complicated PFCs as well. Most of the available data assess the use of plastic stents, but scarce data exists on metal stent management of PFCs. The aim of our study to evaluate the efficacy and safety of a metal stent in the management of PFCs. PATIENTS AND METHODS: Data were collected prospectively on 47 patients diagnosed with PFCs from March 2007 to August 2011 at 3 tertiary care centers. These patients underwent endoscopic transmural placement of a fully covered self-expanding metal stent (FCSEMS) with antimigratory fins of 10 mm diameter. RESULTS: The stent was successfully placed in all patients, and left in place an average of 13 weeks (range 0.4-36 weeks). Etiology of the PFC was biliary pancreatitis (23), pancreas divisum (2), trauma (4), hyperlipidemia (3), alcoholic (8), smoking (2), idiopathic (4), and medication-induced (1). PFCs resolved in 36 patients, for an overall success rate of 77%. Complications included fever (3), stent migration (2) and abdominal pain (1). CONCLUSIONS: The use of FCSEMS is successful in the majority of patients with low complication rates. A large sample-sized RCT is needed to confirm if the resolution of PFCs is long-standing. PMID- 26374581 TI - Starry sky sign: A prevalent sonographic finding in mediastinal tuberculous lymph nodes. AB - BACKGROUND AND OBJECTIVES: We report a prevalent finding in tuberculous lymphadenitis (TL): Starry sky sign, hyperechoic foci without acoustic shadows over a hypoechoic background. MATERIALS AND METHODS: We retrospectively searched the database for a possible relationship of starry sky sign with a specific diagnosis and also the prevalence and accuracy of the finding. RESULTS: Starry sky sign was found in 16 of 31 tuberculous lymph nodes, while none of other lymph nodes (1,015 lymph nodes) exhibited this finding; giving a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of 51.6%, 100%, 100%, 98.5%, and 98.5%, respectively. CONCLUSION: Bacteriologic and histologic findings are gold standard in the diagnosis of tuberculosis, but this finding may guide the bronchoscopist in choosing the more pathologic node within a station and increase the diagnostic yield as it may relate to actively dividing mycobacteria. PMID- 26374582 TI - Endoscopic ultrasound-guided pancreatic pseudocyst cystogastrostomy using a novel self-expandable metal stent with antimigration system: A case series. AB - BACKGROUND AND OBJECTIVES: Development of symptomatic pseudocysts after acute pancreatitis is a common occurrence. Endoscopic ultrasound (EUS)-guided transmural drainage has become the treatment of choice for symptomatic pseudocysts. Following this procedure, stent migration can occur. A recently developed fully covered biliary metal stent with antimigration system has shown promise as an alternative endoprosthetic option for cystogastrostomy. The aim of this study is to describe the success and complications of using covered metal stents with antimigration system to drain pseudocysts at a single tertiary care center. MATERIALS AND METHODS: The patients undergoing cystogastrostomy using the biliary metal stent with antimigration system over the course of a 10-month period (January-November, 2014) were retrospectively reviewed and all the pertinent information including length of the follow-up, age and sex of the patient, pseudocyst size, pseudocyst size at follow-up, and symptom improvement were recorded. RESULTS: Five patients underwent endoscopic cystogastrostomy using a biliary metal stent with antimigration system. The average age of the patients was 57 years, with all the patients being males. The average size of the largest dimension of pseudocyst was 9 cm. The average follow-up time to repeat imaging was 30 days. All the patients had a significant improvement in their pseudocyst size, with two patients having complete resolution, one patient with a residual 2 cm cyst, and another with a residual 5 cm pseudocyst at follow-up. The average size at follow-up was 2 cm. No complications occurred during the follow-up period. No episodes of stent migration occurred. All the patients had symptom improvement at follow-up. CONCLUSION: Using a novel biliary covered self expandable metal stent with antimigration system with EUS guidance to drain pseudocysts appears to be a safe and effective procedure in certain settings. Our experience shows rapid cyst resolution with no complications and no stent migration. This stent gives the providers another option when performing cystogastrostomy. PMID- 26374583 TI - Surgery or EUS-guided choledochoduodenostomy for malignant distal biliary obstruction after ERCP failure. AB - BACKGROUND AND OBJECTIVES: Endoscopic retrograde cholangiopancreatography (ERCP) is the method of choice for drainage in patients with distal malignant biliary obstruction, but it fails in up to 10% of cases. Percutaneous transhepatic cholangiography (PTC) and surgical bypass are the traditional drainage alternatives. This study aimed to compare technical and clinical success, quality of life, and survival of surgical biliary bypass or hepaticojejunostomy (HJT) and endoscopic ultrasound (EUS)-guided choledochoduodenostomy (CDT) in patients with distal malignant bile duct obstruction and failed ERCP. PATIENTS AND METHODS: A prospective, randomized trial was conducted. From March 2011 to September 2013, 32 patients with malignant distal biliary obstruction and failed ERCP were studied. The HJT group consisted of 15 patients and the CDT group consisted of 14 patients. Technical and clinical success, quality of life, and survival were assessed prospectively. RESULTS: Technical success was 94% (15/16) in the HJT group and 88% (14/16) in the CDT group (P = 0.598). Clinical success occurred in 14 (93%) patients in the HJT group and in 10 (71%) patients in the CDT group (P = 0.169). During follow-up, a statistically significant difference was seen in mean functional capacity scores, physical health, pain, social functioning, and emotional and mental health aspects in both techniques (P < 0.05). The median survival time in both groups was the same (82 days). CONCLUSION: Data relating to technical and clinical success, quality of life, and survival were similar in patients who underwent HJT and CDT drainage after failed ERCP for malignant distal biliary obstruction. PMID- 26374584 TI - Interobserver agreement of EUS elastography in the evaluation of solid pancreatic lesions. AB - BACKGROUND AND OBJECTIVES: Previous reports assessing the reproducibility of endoscopic ultrasound elastography (EUS-E) in evaluation of solid pancreatic lesions (SPL) involved only experienced endosonographers. We aimed to assess the interobserver agreement (IOA) of EUS-E in the evaluation of SPL by endoscopists with different levels of experience in EUS and EUS-E. MATERIALS AND METHODS: A cross-sectional observational multicenter study was designed and included 11 endoscopists who were divided into four groups: Group A (long experience in EUS and EUS-E); Group B (short experience in EUS and EUS-E); Group C (long experience in EUS and no experience in EUS-E); and Group D (no experience in EUS or EUS-E). The observers independently classified the patterns of 60 video sequences of EUS E, after a 20-min training session. For each group, we calculated IOA (kappa statistic, k) of EUS-E and the diagnostic accuracy of EUS-E for pancreatic malignancy, by comparing the pattern of EUS-E indicative of malignancy (heterogeneous or homogenous blue) with the final diagnosis. RESULTS: The overall IOA was moderate (k = 0.42; 95% confidence interval (CI) 0.33-0.52). The IOA of Group A (k = 0.80; 95% CI 0.65-1.00) was significantly higher than that of Groups B (k = 0.54; 95%CI 0.40-0.71), C (k = 0.54; 95%CI 0.39-0.68), and D (k = 0.28; 95%CI 0.14-0.40). IOA of Groups B and C was not significantly different, but it was significantly higher than that of Group D. The diagnostic accuracy of Group A (area under the curve under summary receiver operating characteristic (AUROC) = 0.83; 95%CI 0.75-0.90) was not significantly different from that of Group B (AUROC = 0.77; 95%CI 0.71-0.83), but it was significantly higher than that of Groups C (AUROC = 0.74; 95%CI 0.67-0.81) and D (AUROC = 0.74; 95%CI 0.67-0.81). No significant difference was seen between Groups B, C, and D for diagnostic accuracy. CONCLUSION: EUS-E is reproducible in the evaluation of SPL, even between endoscopists with no or limited experience in EUS and/or EUS-E. Reproducibility and diagnostic accuracy increase with experience in EUS and EUS E. PMID- 26374585 TI - Hepatogastrostomy by EUS for malignant afferent loop obstruction after duodenopancreatectomy. AB - One of the most difficult biliary drainages is the recurrence and stenosis on afferent loop after surgery. We report an original case of hepaticogastrostomy (HGE) in a patient who had malignant stenosis of afferent loop after cephalic duodenopancreatectomy (CDP). After failure of the gastrointestinal stent, two metal self-expandable stents were placed by endoscopic ultrasound (EUS) after puncture of the dilated left hepatic duct. On clinical improvement and disappearance of jaundice, palliative chemotherapy was started. PMID- 26374586 TI - A duodenal gastrointestinal stromal tumor with a large central area of fluid and gas due to fistulization into the duodenal lumen, mimicking a large duodenal diverticulum. AB - Gastrointestinal stromal tumors (GISTs) can occur anywhere along the gastrointestinal tract especially the stomach and upper small bowel. They are usually solid, but cystic degeneration, necrosis, and focal hemorrhage have been described in larger tumors leading to central necrotic cavitation. The most sensitive marker of GIST is CD117 (c-kit). In computed tomography (CT) scan, it is often difficult to decide the origin of the primary tumor, especially in large GISTs. We report an incidental case of a large duodenal GIST fistulizing into the second part of the duodenum with a large amount of fluid and gas inside, mistaken for a cystic pancreatic neoplasm by CT and mistaken for a duodenal diverticulum by endoscopic ultrasound. PMID- 26374587 TI - Creation of multiple transluminal gateway during endoscopic ultrasound-guided drainage of pancreatic necrosis by enlarging tract of impending rupture in duodenum. AB - Necrotic pancreatic collections are difficult to treat endoscopically due to a concern for inadequate drainage of the necrotic debris. Multiple techniques including the use of metallic stents, endoscopic necrosectomy and use of hybrid approaches utilizing endoscopic and percutaneous approaches have been described for the management of pancreatic necrotic collections. Furthermore, multiple transluminal gateway technique has been used to create endosonography guided multiple tracts to drain a perigastric or periduodenal collection. We hereby report about a patient with walled off necrosis resulting as a complication of alcohol related acute pancreatitis that was drained using endoscopic ultrasound guided approach. However, a spontaneous cystoduodenal fistula was used to create another tract and place transmural stents resulting in a quick resolution of symptoms. PMID- 26374588 TI - Endoscopic ultrasound-guided transmural drainage of infected pancreatic necrosis developing 2 years after acute pancreatitis. AB - This is a case report of endoscopic ultrasound guided transmural drainage of a large infected pancreatic necrosis. The infected necrosis was treated by placement of a fully covered metal stent with subsequent endoscopic necrosectomy to remove solid debris. The case is notable for the fact that the patient developed infection of a long-standing and previously stable area of walled-off pancreatic necrosis 2 years after it formed. We believe this is the longest time ever reported between necrotizing pancreatitis and the development of infected pancreatic necrosis. PMID- 26374589 TI - An unusual case of large symptomatic Brunner's gland adenoma: Endoscopic ultrasound imaging. PMID- 26374590 TI - Mediastinal sarcoidosis diagnosed by endobronchial ultrasound in a patient with Sjogren's syndrome. PMID- 26374591 TI - Are rigid probes sufficient to provide reliable data for rectal cancer staging? PMID- 26374592 TI - Endoscopic ultrasonography-guided drainage of a pancreatic pseudocyst one week after formation. PMID- 26374593 TI - Feasibility and safety of cardiopulmonary exercise testing in children with pulmonary hypertension. AB - BACKGROUND: Cardiopulmonary exercise testing helps prognosticate and guide treatment in adults with pulmonary hypertension. Concerns regarding its feasibility and safety limit its use in children with pulmonary hypertension. We aimed to assess the feasibility and safety of cardiopulmonary exercise testing in a large paediatric pulmonary hypertension cohort. METHODS: We reviewed all consecutive cardiopulmonary exercise tests performed between March, 2004 and November, 2013. The exclusion criteria were as follows: height <120 cm, World Health Organization class IV, history of exercise-induced syncope, or significant ischaemia/arrhythmias. Significant events recorded were as follows: patient reported symptoms, arrhythmias, electrocardiogram abnormalities, and abnormal responses of arterial O2 saturation. RESULTS: A total of 98 children underwent 167 cardiopulmonary exercise tests. The median age was 14 years (inter-quartile range 10-15 years). Peak oxygen uptake was 20.4+/-7.3 ml/kg/minute, corresponding to 51.8+/-18.3% of the predicted value. Peak respiratory quotient was 1.08+/ 0.16. All the tests except two were maximal, being terminated prematurely for clinical reasons. Baseline Oxygen saturation was 93.3+/-8.8% and was 81.2+/-19.5% at peak exercise. A drop in arterial O2 saturation >20% was observed in 23.5% of the patients. Moreover, five patients (3.0%) experienced dizziness, one requiring termination of cardiopulmonary exercise testing; five children (3.0%) experienced chest pain, with early cardiopulmonary exercise test termination in one patient. No significant arrhythmias or electrocardiogram changes were observed. CONCLUSION: Exercise testing in non-severely symptomatic children with pulmonary hypertension is safe and practical, and can be performed in a large number of children with pulmonary hypertension in a controlled environment with an experienced team. Side-effects were not serious and were resolved promptly with test termination. PMID- 26374594 TI - Actinide (An = Th-Pu) dimetallocenes: promising candidates for metal-metal multiple bonds. AB - Synthesis of complexes with direct actinide-actinide (An-An) bonding is an experimental 'holy grail' in actinide chemistry. In this work, a series of actinide dimetallocenes An2Cp (Cp(*) = C5(CH3)5, An = Th-Pu) with An-An multiple bonds have been systematically investigated using quantum chemical calculations. The coaxial Cp(*)-An-An-Cp(*) structures are found to be the most stable species for all the dimetallocenes. A Th-Th triple bond is predicted in the Th2Cp complex, and the calculated An-An bond orders decrease across the actinide series from Pa to Pu. The covalent character of the An-An bonds is analyzed by using natural bond orbitals (NBO), molecular orbitals (MO), the quantum theory of atoms in molecules (QTAIM), and electron density difference (EDD). While Th 6d orbitals dominate the Th-Th bonds in Th2Cp, the An 6d-orbital characters decrease and 5f orbital characters increase for complexes from Pa2Cp to Pu2Cp. All these actinide dimetallocenes are stable in the gas phase relative to the AnCp(*) reference at room temperature. Based on the reactions of AnCp and An, Th2Cp, Pa2Cp and possibly also U2Cp should be accessible as isolated molecules under suitable synthetic conditions. Our results shed light on the molecular design of ligands for stabilizing actinide-actinide multiple bonds. PMID- 26374595 TI - Editorial Comment from Dr. Rassweiler to Application of nephrostomy tubes with balloon after percutaneous nephrolithotomy: A randomized controlled clinical trial. PMID- 26374597 TI - Genetic Linkage Mapping of Economically Important Traits in Cultivated Tetraploid Potato (Solanum tuberosum L.). AB - The objective of this study was to construct a single nucleotide polymorphism (SNP)-based genetic map at the cultivated tetraploid level to locate quantitative trait loci (QTL) contributing to economically important traits in potato (Solanum tuberosum L.). The 156 F1 progeny and parents of a cross (MSL603) between "Jacqueline Lee" and "MSG227-2" were genotyped using the Infinium 8303 Potato Array. Furthermore, the progeny and parents were evaluated for foliar late blight reaction to isolates of the US-8 genotype of Phytophthora infestans (Mont.) de Bary and vine maturity. Linkage analyses and QTL mapping were performed using a novel approach that incorporates allele dosage information. The resulting genetic maps contained 1972 SNP markers with an average density of 1.36 marker per cM. QTL mapping identified the major source of late blight resistance in "Jacqueline Lee." The best SNP marker mapped ~0.54 Mb from a resistance hotspot on the long arm of chromosome 9. For vine maturity, the major-effect QTL was located on chromosome 5 with allelic effects from both parents. A candidate SNP marker for this trait mapped ~0.25 Mb from the StCDF1 gene, which is a candidate gene for the maturity trait. The identification of markers for P. infestans resistance will enable the introgression of multiple sources of resistance through marker assisted selection. Moreover, the discovery of a QTL for late blight resistance not linked to the QTL for vine maturity provides the opportunity to use marker assisted selection for resistance independent of the selection for vine maturity classifications. PMID- 26374596 TI - Genome-Wide Association Study of Ureide Concentration in Diverse Maturity Group IV Soybean [Glycine max (L.) Merr.] Accessions. AB - Ureides are the N-rich products of N-fixation that are transported from soybean nodules to the shoot. Ureides are known to accumulate in leaves in response to water-deficit stress, and this has been used to identify genotypes with reduced N fixation sensitivity to drought. Our objectives in this research were to determine shoot ureide concentrations in 374 Maturity Group IV soybean accessions and to identify genomic regions associated with shoot ureide concentration. The accessions were grown at two locations (Columbia, MO, and Stuttgart, AR) in 2 yr (2009 and 2010) and characterized for ureide concentration at beginning flowering to full bloom. Average shoot ureide concentrations across all four environments (two locations and two years) and 374 accessions ranged from 12.4 to 33.1 umol g( 1) and were comparable to previously reported values. SNP-ureide associations within and across the four environments were assessed using 33,957 SNPs with a MAF >=0.03. In total, 53 putative loci on 18 chromosomes were identified as associated with ureide concentration. Two of the putative loci were located near previously reported QTL associated with ureide concentration and 30 loci were located near genes associated with ureide metabolism. The remaining putative loci were not near chromosomal regions previously associated with shoot ureide concentration and may mark new genes involved in ureide metabolism. Ultimately, confirmation of these putative loci will provide new sources of variation for use in soybean breeding programs. PMID- 26374598 TI - Harnessing novel modalities: field carcinogenesis detection for personalizing prostate cancer management. PMID- 26374599 TI - Insulin resistance and vascular dysfunction in chronic kidney disease: mechanisms and therapeutic interventions. AB - Insulin resistance (IR) is a novel cardiovascular risk factor that has been implicated in the pathogenesis of cardiovascular disease (CVD) in patients with chronic kidney disease (CKD). Beyond its metabolic effects, insulin can potentially mediate the increased risk for CVD through its vasoactive properties. This review examines key clinical data and potential mechanisms linking IR and cardiovascular risk in CKD. While lifestyle interventions and pharmacotherapies with known insulin-sensitizing properties are promising therapeutic targets to reduce the CVD burden in this population, clinical trial data on the effect of insulin sensitization on vascular function in CKD are either lacking or conflicting and are limited by small sample size and short duration of intervention. Affirming the role of IR in lowering CVD risk in CKD will require prospective randomized controlled studies with sufficient sample size and hard clinical outcomes. Future research efforts should be directed at assessing the efficacy, safety and mechanisms by which novel insulin sensitizers such as bile acid sequestrant, selective and dual peroxisome proliferator-activated receptor modulators and modulators of gut microbiota and uraemic toxins alter vascular function in patients with CKD. PMID- 26374601 TI - Membranes of MnO Beading in Carbon Nanofibers as Flexible Anodes for High Performance Lithium-Ion Batteries. AB - Freestanding yet flexible membranes of MnO/carbon nanofibers are successfully fabricated through incorporating MnO2 nanowires into polymer solution by a facile electrospinning technique. During the stabilization and carbonization processes of the as-spun membranes, MnO2 nanowires are transformed to MnO nanoparticles coincided with a conversion of the polymer from an amorphous state to a graphitic structure of carbon nanofibers. The hybrids consist of isolated MnO nanoparticles beading in the porous carbon and demonstrate superior performance when being used as a binder-free anode for lithium-ion batteries. With an optimized amount of MnO (34.6 wt%), the anode exhibits a reversible capacity of as high as 987.3 mAh g( 1) after 150 discharge/charge cycles at 0.1 A g(-1), a good rate capability (406.1 mAh g(-1) at 3 A g(-1)) and an excellent cycling performance (655 mAh g( 1) over 280 cycles at 0.5 A g(-1)). Furthermore, the hybrid anode maintains a good electrochemical performance at bending state as a flexible electrode. PMID- 26374600 TI - The effect of parathyroidectomy on patient survival in secondary hyperparathyroidism. AB - BACKGROUND: Secondary hyperparathyroidism is a common condition in patients with end-stage renal disease and is associated with osteoporosis and cardiovascular disease. Despite improved medical treatment, parathyroidectomy (PTX) is still necessary for many patients on renal replacement therapy. The aim of this study was to evaluate the effect of PTX on patient survival. METHODS: A nested index referent study was performed within the Swedish Renal Registry (SRR). Patients on maintenance dialysis and transplantation at the time of PTX were analysed separately. The PTX patients in each of these strata were matched for age, sex and underlying renal diseases with up to five referent patients who had not undergone PTX. To calculate survival time and hazard ratios, indexes and referents were assigned the calendar date (d) of the PTX of the index patient. The risk of death after PTX was calculated using crude and adjusted Cox proportional hazards regressions. RESULTS: There were 20 056 patients in the SRR between 1991 and 2009. Of these, 579 (423 on dialysis and 156 with a renal transplant at d) incident patients with PTX were matched with 1234/892 non-PTX patients. The adjusted relative risk of death was a hazard ratio (HR) of 0.80 [95% confidence interval (CI) 0.65-0.99] for dialysis patients at d who had undergone PTX compared with matched patients who had not. Corresponding results for the patients with a renal allograft at d were an HR of 1.10 (95% CI 0.71 1.70). CONCLUSIONS: PTX was associated with improved survival in patients on maintenance dialysis but not in patients with renal allograft. PMID- 26374603 TI - Disclination mediated dynamic recrystallization in metals at low temperature. AB - Recrystallization is one of the most important physical phenomena in condensed matter that has been utilized for materials processing for thousands of years in human history. It is generally believed that recrystallization is thermally activated and a minimum temperature must be achieved for the necessary atomic mechanisms to occur. Here, using atomistic simulations, we report a new mechanism of dynamic recrystallization that can operate at temperature as low as T = 10 K in metals during deformation. In contrast to previously proposed dislocation based models, this mechanism relies on the generation of disclination quadrupoles, which are special defects that form during deformation when the grain boundary migration is restricted by structural defects such as triple junctions, cracks or obstacles. This mechanism offers an alternative explanation for the grain refinement in metals during severe plastic deformation at cryogenic temperature and may suggest a new method to tailor the microstructure in general crystalline materials. PMID- 26374602 TI - The association between an ultrabrief cognitive screening in older adults and hospital outcomes. AB - BACKGROUND: Though often recommended, hospital cognitive assessment is infrequently completed due to clinical and time constraints. OBJECTIVE: This analysis aimed to evaluate the relationship between performance on ultrabrief cognitive screening instruments and hospital outcomes. DESIGN: This is a secondary data analysis of a quality improvement project. SETTING: Tertiary Veterans Administration hospital in New England. PATIENTS: Patients, >= 60 years old, admitted to the hospital. INTERVENTION: None. MEASUREMENTS: Upon admission, patients were administered 2 cognitive screening tools. The modified Richmond Agitation and Sedation Scale (mRASS) is a measure of arousal that can be completed in 15 seconds. The months of the year backward (MOYB) is a measure of attention that can be administered in <=1 minute. In-hospital outcomes included restraints and mortality, whereas discharge outcomes included length of stay, discharge not home, and variable direct costs. Risk ratios were calculated for dichotomous outcomes and unadjusted Poisson regression for continuous outcomes. RESULTS: Patients (n = 3232) were screened. Altered arousal occurred in 15% of patients (n = 495); incorrect MOYB was recorded in 45% (n = 1457). Relative to those with normal arousal and attention, those with abnormal mRASS and incorrect MOYB had increased length of stay (incident rate ratio [IRR]: 1.23, 95% confidence interval [CI]: 1.17-1.30); restraint use (risk ratio [RR]: 5.05, 95% CI: 3.29-7.75), in-hospital mortality (RR: 3.46, 95% CI: 1.24-9.63), and decreased discharge home (RR: 2.97, 95% CI: 2.42-3.64). Hospital variable direct costs were slightly, but not significantly, higher (IRR: 1.02, 95% CI: 0.88 1.17). CONCLUSION: Impaired performance on ultrabrief cognitive assessments of arousal and attention provide valuable insights regarding hospital outcomes. PMID- 26374604 TI - HIV prevention and care services for female sex workers: efficacy of a targeted community-based intervention in Burkina Faso. AB - INTRODUCTION: Although interventions to control HIV among high-risk groups such as female sex workers (FSW) are highly recommended in Africa, the contents and efficacy of these interventions are unclear. We therefore designed a comprehensive dedicated intervention targeting young FSW and assessed its impact on HIV incidence in Burkina Faso. METHODS: Between September 2009 and September 2011 we conducted a prospective, interventional cohort study of FSW aged 18 to 25 years in Ouagadougou, with quarterly follow-up for a maximum of 21 months. The intervention combined prevention and care within the same setting, consisting of peer-led education sessions, psychological support, sexually transmitted infections and HIV care, general routine health care and reproductive health services. At each visit, behavioural characteristics were collected and HIV, HSV 2 and pregnancy were tested. We compared the cohort HIV incidence with a modelled expected incidence in the study population in the absence of intervention, using data collected at the same time from FSW clients. RESULTS: The 321 HIV-uninfected FSW enrolled in the cohort completed 409 person-years of follow-up. No participant seroconverted for HIV during the study (0/409 person-years), whereas the expected modelled number of HIV infections were 5.05/409 person-years (95% CI, 5.01-5.08) or 1.23 infections per 100 person-years (p=0.005). This null incidence was related to a reduction in the number of regular partners and regular clients, and by an increase in consistent condom use with casual clients (adjusted odds ratio (aOR)=2.19; 95% CI, 1.16-4.14, p=0.01) and with regular clients (aOR=2.18; 95% CI, 1.26-3.76, p=0.005). CONCLUSIONS: Combining peer-based prevention and care within the same setting markedly reduced the HIV incidence among young FSW in Burkina Faso, through reduced risky behaviours. PMID- 26374606 TI - Mast Cell Stabilization Ameliorates Autoimmune Anti-Myeloperoxidase Glomerulonephritis. AB - Observations in experimental murine myeloperoxidase (MPO)-ANCA-associated vasculitis (AAV) show mast cells degranulate, thus enhancing injury as well as producing immunomodulatory IL-10. Here we report that, compared with biopsy specimens from control patients, renal biopsy specimens from 44 patients with acute AAV had more mast cells in the interstitium, which correlated with the severity of tubulointerstitial injury. Furthermore, most of the mast cells were degranulated and spindle-shaped in patients with acute AAV, indicating an activated phenotype. We hypothesized that the mast cell stabilizer disodium cromoglycate would attenuate mast cell degranulation without affecting IL-10 production. We induced anti-MPO GN by immunizing mice with MPO and a low dose of anti-glomerular basement membrane antibody. When administered before or after induction of MPO autoimmunity in these mice, disodium cromoglycate attenuated mast cell degranulation, development of autoimmunity, and development of GN, without diminishing IL-10 production. In contrast, administration of disodium cromoglycate to mast cell-deficient mice had no effect on the development of MPO autoimmunity or GN. MPO-specific CD4(+) effector T cell proliferation was enhanced by co-culture with mast cells, but in the presence of disodium cromoglycate, proliferation was inhibited and IL-10 production was enhanced. These results indicate that disodium cromoglycate blocks injurious mast cell degranulation specifically without affecting the immunomodulatory role of these cells. Thus as a therapeutic, disodium cromoglycate may substantially enhance the regulatory role of mast cells in MPO-AAV. PMID- 26374607 TI - Light Chain Proximal Tubulopathy: Clinical and Pathologic Characteristics in the Modern Treatment Era. AB - Light chain proximal tubulopathy (LCPT) is characterized by cytoplasmic inclusions of monoclonal LC within proximal tubular cells. The significance of crystalline versus noncrystalline LCPT and the effect of modern therapies are unknown. We reported the clinical-pathologic features of 40 crystalline and six noncrystalline LCPT patients diagnosed between 2000 and 2014. All crystalline LCPTs were kappa-restricted and displayed acute tubular injury. One-third of noncrystalline LCPT patients displayed lambda-restriction or acute tubular injury. Only crystalline LCPT frequently required antigen retrieval to demonstrate monoclonal LC by immunofluorescence. In five of 38 patients, crystals were not detectable by light microscopy, but they were visible by electron microscopy. Hematolymphoid neoplasms, known before biopsy in only 15% of patients, included 21 monoclonal gammopathies of renal significance; 15 multiple myelomas; seven smoldering multiple myelomas; and three other neoplasms. Biopsy indications included Fanconi syndrome (38%; all with crystalline LCPT), renal insufficiency (83%), and proteinuria (98%). Follow-up was available for 30 (75%) patients with crystalline LCPT and all six patients with noncrystalline LCPT, of whom 11 underwent stem cell transplant, 16 received chemotherapy only, and nine were untreated. Complete or very good partial hematologic remissions occurred in six of 22 treated crystalline LCPT patients. By multivariable analysis, the only independent predictor of final eGFR was initial eGFR, highlighting the importance of early detection. All patients with crystalline LCPT treated with stem cell transplant had stable or improved kidney function, indicating the effectiveness of aggressive therapy in selected patients. PMID- 26374608 TI - Partial Complement Factor H Deficiency Associates with C3 Glomerulopathy and Thrombotic Microangiopathy. AB - The complement-mediated renal diseases C3 glomerulopathy (C3G) and atypical hemolytic uremic syndrome (aHUS) strongly associate with inherited and acquired abnormalities in the regulation of the complement alternative pathway (AP). The major negative regulator of the AP is the plasma protein complement factor H (FH). Abnormalities in FH result in uncontrolled activation of C3 through the AP and associate with susceptibility to both C3G and aHUS. Although previously developed FH-deficient animal models have provided important insights into the mechanisms underlying susceptibility to these unique phenotypes, these models do not entirely reproduce the clinical observations. FH is predominantly synthesized in the liver. We generated mice with hepatocyte-specific FH deficiency and showed that these animals have reduced plasma FH levels with secondary reduction in plasma C3. Unlike mice with complete FH deficiency, hepatocyte-specific FH deficient animals developed neither plasma C5 depletion nor accumulation of C3 along the glomerular basement membrane. In contrast, subtotal FH deficiency associated with mesangial C3 accumulation consistent with C3G. Although there was no evidence of spontaneous thrombotic microangiopathy, the hepatocyte-specific FH deficient animals developed severe C5-dependent thrombotic microangiopathy after induction of complement activation within the kidney by accelerated serum nephrotoxic nephritis. Taken together, our data indicate that subtotal FH deficiency can give rise to either spontaneous C3G or aHUS after a complement activating trigger within the kidney and that the latter is C5 dependent. PMID- 26374609 TI - Associations between Deceased-Donor Urine Injury Biomarkers and Kidney Transplant Outcomes. AB - Assessment of deceased-donor organ quality is integral to transplant allocation practices, but tools to more precisely measure donor kidney injury and better predict outcomes are needed. In this study, we assessed associations between injury biomarkers in deceased-donor urine and the following outcomes: donor AKI (stage 2 or greater), recipient delayed graft function (defined as dialysis in first week post-transplant), and recipient 6-month eGFR. We measured urinary concentrations of microalbumin, neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), IL-18, and liver-type fatty acid binding protein (L-FABP) from 1304 deceased donors at organ procurement, among whom 112 (9%) had AKI. Each biomarker strongly associated with AKI in adjusted analyses. Among 2441 kidney transplant recipients, 31% experienced delayed graft function, and mean+/-SD 6-month eGFR was 55.7+/-23.5 ml/min per 1.73 m(2) In analyses adjusted for donor and recipient characteristics, higher donor urinary NGAL concentrations associated with recipient delayed graft function (highest versus lowest NGAL tertile relative risk, 1.21; 95% confidence interval, 1.02 to 1.43). Linear regression analyses of 6-month recipient renal function demonstrated that higher urinary NGAL and L-FABP concentrations associated with slightly lower 6-month eGFR only among recipients without delayed graft function. In summary, donor urine injury biomarkers strongly associate with donor AKI but provide limited value in predicting delayed graft function or early allograft function after transplant. PMID- 26374611 TI - Electrospun Flexible Coaxial Nanoribbons Endowed With Tuned and Simultaneous Fluorescent Color-Electricity-Magnetism Trifunctionality. AB - In order to develop new-typed multifunctional nanocomposites, fluorescent electrical-magnetic trifunctional coaxial nanoribbons with tunable fluorescent color, including white-light emission, have been successfully fabricated via coaxial electrospinning technology. Each stripe of coaxial nanoribbon is composed of a Fe3O4/PMMA core and a [Eu(BA)3phen+Dy(BA)3phen]/PANI/PMMA (PMMA = polymethyl methacrylate, BA = benzoic acid, phen = phenanthroline, polyaniline = PANI) shell. X-ray diffractometry (XRD), field emission scanning electron microscopy (FE-SEM), biological microscopy (BM), vibrating sample magnetometry (VSM), energy dispersive spectrometry (EDS), Hall effect measurement system and photoluminescence (PL) spectroscopy were employed to characterize the coaxial nanoribbons. Emitting color of the coaxial nanoribbons can be tuned by adjusting the contents of Dy(BA)3phen, Eu(BA)3phen, PANI and Fe3O4 in a wide color range of blue-white-orange under the excitation of 273-nm single-wavelength ultraviolet light. The coaxial nanoribbons simultaneously possess excellent luminescent performance, electrical conduction and magnetism compared with the counterpart composite nanoribbons. Furthermore, the electrical and magnetic performances of the coaxial nanoribbons also can be tunable by adding different quantities of PANI and Fe3O4 nanoparticles, respectively. The obtained coaxial nanoribbons have promising applications in many areas, such as electromagnetic interference shielding, microwave absorption, molecular electronics, biomedicine, future nanomechanics and display fields. PMID- 26374610 TI - Modulation of Polycystic Kidney Disease Severity by Phosphodiesterase 1 and 3 Subfamilies. AB - Aberrant intracellular calcium levels and increased cAMP signaling contribute to the development of polycystic kidney disease (PKD). cAMP can be hydrolyzed by various phosphodiesterases (PDEs). To examine the role of cAMP hydrolysis and the most relevant PDEs in the pathogenesis of PKD, we examined cyst development in Pde1- or Pde3-knockout mice on the Pkd2(-/WS25) background (WS25 is an unstable Pkd2 allele). These PDEs were selected because of their importance in cross-talk between calcium and cyclic nucleotide signaling (PDE1), control of cell proliferation and cystic fibrosis transmembrane conductance regulator (CFTR) driven fluid secretion (PDE3), and response to vasopressin V2 receptor activation (both). In Pkd2(-/WS25) mice, knockout of Pde1a, Pde1c, or Pde3a but not of Pde1b or Pde3b aggravated the development of PKD and was associated with higher levels of protein kinase A-phosphorylated (Ser133) cAMP-responsive binding protein (P CREB), activating transcription factor-1, and CREB-induced CRE modulator proteins in kidney nuclear preparations. Immunostaining also revealed higher expression of P-CREB in Pkd2(-/) (WS25);Pde1a(-/-), Pkd2(-) (/WS25);Pde1c(-/-), and Pkd2(-/) (WS25);Pde3a(-/-) kidneys. The cystogenic effect of desmopressin administration was markedly enhanced in Pkd2(-/WS25);Pde3a(-/-) mice, despite PDE3 accounting for only a small fraction of renal cAMP PDE activity. These observations show that calcium- and calmodulin-dependent PDEs (PDE1A and PDE1C) and PDE3A modulate the development of PKD, possibly through the regulation of compartmentalized cAMP pools that control cell proliferation and CFTR-driven fluid secretion. Treatments capable of increasing the expression or activity of these PDEs may, therefore, retard the development of PKD. PMID- 26374612 TI - Bactericidal effects of triclosan in soap both in vitro and in vivo. AB - OBJECTIVES: On December 2013, the US FDA proposed a rule stating that manufacturers must provide data to demonstrate that antibacterial soap is more effective than plain soap or water. The objective of the present study was to examine the in vitro and in vivo bactericidal effect of triclosan (the most widely used antiseptic agent in soap) in soap. METHODS: Twenty bacterial strains (proposed by the FDA) were exposed to plain and antibacterial soaps (the same formulation as plain soap, but containing 0.3% triclosan) for 20 s at 22 degrees C (room temperature) and 40 degrees C (warm temperature). The temperature and time were selected to simulate the hand washing conditions and procedures used by consumers. The triclosan concentration of 0.3% is the maximum allowed by law. The decontamination efficacy of plain soap and antibacterial soap was also examined in vivo: the hands of volunteers were artificially inoculated with Serratia marcescens. RESULTS: There was no significant difference (P > 0.05) in bactericidal activity between plain soap and antibacterial soap at either test temperature. However, antibacterial soap showed significantly greater bactericidal effects after 9 h. These results suggest that although triclosan containing soap does have antibacterial activity, the effects are not apparent during the short time required for hand washing. CONCLUSIONS: Antibacterial soap containing triclosan (0.3%) was no more effective than plain soap at reducing bacterial contamination when used under 'real-life' conditions. The present study provides practical information that may prove useful for both industry and governments. PMID- 26374613 TI - Detection of carbapenemase activity in Enterobacteriaceae: comparison of the carbapenem inactivation method versus the Carba NP test. PMID- 26374614 TI - Potential of trans fats policies to reduce socioeconomic inequalities in mortality from coronary heart disease in England: cost effectiveness modelling study. AB - OBJECTIVES: To determine health and equity benefits and cost effectiveness of policies to reduce or eliminate trans fatty acids from processed foods, compared with consumption remaining at most recent levels in England. DESIGN: Epidemiological modelling study. SETTING: Data from National Diet and Nutrition Survey, Low Income Diet and Nutrition Survey, Office of National Statistics, and health economic data from other published studies PARTICIPANTS: Adults aged >=25, stratified by fifths of socioeconomic circumstance. INTERVENTIONS: Total ban on trans fatty acids in processed foods; improved labelling of trans fatty acids; bans on trans fatty acids in restaurants and takeaways. MAIN OUTCOME MEASURES: Deaths from coronary heart disease prevented or postponed; life years gained; quality adjusted life years gained. Policy costs to government and industry; policy savings from reductions in direct healthcare, informal care, and productivity loss. RESULTS: A total ban on trans fatty acids in processed foods might prevent or postpone about 7200 deaths (2.6%) from coronary heart disease from 2015-20 and reduce inequality in mortality from coronary heart disease by about 3000 deaths (15%). Policies to improve labelling or simply remove trans fatty acids from restaurants/fast food could save between 1800 (0.7%) and 3500 (1.3%) deaths from coronary heart disease and reduce inequalities by 600 (3%) to 1500 (7%) deaths, thus making them at best half as effective. A total ban would have the greatest net cost savings of about L265m (?361m, $415m) excluding reformulation costs, or L64m if substantial reformulation costs are incurred outside the normal cycle. CONCLUSIONS: A regulatory policy to eliminate trans fatty acids from processed foods in England would be the most effective and equitable policy option. Intermediate policies would also be beneficial. Simply continuing to rely on industry to voluntary reformulate products, however, could have negative health and economic outcomes. PMID- 26374615 TI - Dietary fats, health, and inequalities. PMID- 26374616 TI - Evidence about electronic cigarettes: a foundation built on rock or sand? PMID- 26374617 TI - MPs criticise Hunt for unclear plans on seven day NHS and "attacks" on NHS staff, but others praise him. PMID- 26374618 TI - Effect of calcium chloride treatments on calcium content, anthracnose severity and antioxidant activity in papaya fruit during ambient storage. AB - BACKGROUND: There have been no reports on the effects of preharvest calcium application on anthracnose disease severity, antioxidant activity and cellular changes during ambient storage of papaya, and therefore the objective of this study was to investigate these effects. RESULTS: Higher calcium concentrations (1.5 and 2% w/v) increased calcium concentration in the peel and pulp tissues, maintained firmness, and reduced anthracnose incidence and severity. While leakage of calcium-treated fruit was lower for 1.5 and 2% calcium treatments compared to the control, microscopic results confirmed that pulp cell wall thickness was higher after 6 days in storage, for the 2% calcium treatment compared to the control. Calcium-treated fruit also had higher total antioxidant activity and total phenolic compounds during storage. CONCLUSION: Calcium chloride, especially at higher concentrations, is effective in maintaining papaya fruit quality during ambient storage. (c) 2015 Society of Chemical Industry. PMID- 26374619 TI - Non-pharmacological interventions to manage fatigue and psychological stress in children and adolescents with cancer: an integrative review. AB - Cancer-related fatigue (CRF) is the most stressful and prevalent symptom in paediatric oncology patients. This integrative review aimed to identify, analyse and synthesise the evidence of non-pharmacological intervention studies to manage fatigue and psychological stress in a paediatric population with cancer. Eight electronic databases were used for the search: PubMed, Web of Science, CINAHL, LILACS, EMBASE, SCOPUS, PsycINFO and the Cochrane Library. Initially, 273 articles were found; after the exclusion of repeated articles, reading of the titles, abstracts and the full articles, a final sample of nine articles was obtained. The articles were grouped into five categories: physical exercise, healing touch, music therapy, therapeutic massage, nursing interventions and health education. Among the nine studies, six showed statistical significance regarding the fatigue and/or stress levels, showing that the use of the interventions led to symptoms decrease. The most frequently tested intervention was programmed physical exercises. It is suggested that these interventions are complementary to conventional treatment and that their use can indicate an improvement in CRF and psychological stress. PMID- 26374620 TI - Birth weight and asthma incidence by asthma phenotype pattern in a racially diverse cohort followed through adolescence. AB - OBJECTIVE: Low birth weight (LBW) has been shown to be an independent risk factor for asthma. We hypothesized that LBW would have its greatest impact on early onset disease. METHODS: A racially diverse cohort of children born from 1983 to 1985 at two hospitals, one urban and one suburban in the same metropolitan area, and oversampled for babies weighing <=2500 g, was identified retrospectively when the children were 6 years of age and followed periodically. At the age 17 years study visit, cohort members and their parent/guardians were separately interviewed face-to-face regarding the subject's history of asthma using the standardized ISAAC questionnaire. We measured the cumulative incidence of asthma from birth through adolescence defined by age of diagnosis and persistence/remittance. RESULTS: Six-hundred and eighty teens (82.6% of the original cohort) were included in the analyses, 387 with LBW and 293 of normal birth weight. The prevalence of physician-diagnosed "Current Asthma" was associated with LBW (p = 0.003 for trend), with patterns stronger in males and whites. LBW was associated most strongly with Late Onset Persistent asthma (current asthma that was diagnosed after 8 years); p for trend 0.032. This trend was again most evident in males and whites. None of the asthma categories classified as "remittent" were statistically associated with LBW. CONCLUSIONS: LBW was not associated with diagnosed asthma that remitted before age 17 years. LBW was associated with asthma diagnosis in mid-childhood that persisted through adolescence, suggesting that the asthmagenic effects of LBW can become evident post the early years of childhood and persist into adulthood. PMID- 26374621 TI - Development and validation of an UHPLC-MS/MS method for the determination of mycotoxins in grass silages. AB - An ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC MS/MS) multi-mycotoxin analytical method was developed to simultaneously identify and quantify 20 mycotoxins in grass silages, inclusive of mycotoxins that are currently regulated in European Union feeds. Extraction of mycotoxins from dried grass silages was performed using of a modified QuEChERS extraction employing an acidified aqueous extraction (0.1 N HCl) with no further clean-up. Following chromatographic separation, analytes were detected using a fast polarity switching MS/MS method that allowed both positive and negative ions to be analysed from a single injection, thus the reducing time and cost of analysis. The limits of detection and quantification ranged between 3 ug kg(-1) DM (aflatoxin B1, beauvericin and enniatin A and A1) and 200 ug kg(-1) DM (deoxynivalenol), and between 10 ug kg(-1) DM (aflatoxin B1, beauvericin and enniatin A1) and 500 ug kg(-1) DM (deoxynivalenol), respectively. Inter-assay accuracy and precision ranged between 90% and 107% and between 3.9% and 15.0% CV, respectively. The accuracy of the method was assessed through the application to a range of incurred samples in an inter-laboratory study. PMID- 26374622 TI - Identification and functional analysis of acute myeloid leukemia susceptibility associated single nucleotide polymorphisms at non-protein coding regions of RUNX1. AB - Little is known about the susceptibility to acute myeloid leukemia. We aim to search non-protein coding regions of key hematopoiesis transcription factors for genetic variations associated with acute myeloid leukemia susceptibility. We genotyped SNPs of RUNX1 P1 promoter, P2 promoter, +23 enhancer, intron 5.2 enhancer, PU.1 promoter, CEBPA promoter, and CEBPE promoter from acute myeloid leukemia patients and healthy controls. Rs2249650 and rs2268276 at RUNX1 intron 5.2 enhancer were found to be associated with acute myeloid leukemia susceptibility. Artificial reporters containing different rs2249650 and rs2268276 alleles showed differential activities in the K562 cell line, a human immortalized myeloid leukemia line. Rs2249650 contributes to reporter activities more than rs2268276. Gel shift assay is consistent with the luciferase assay. Supershift assay indicated that one potential binding protein was PU.1. To sum up, rs2268276 and especially rs2249650 may be qualified as new acute myeloid leukemia susceptibility-associated SNPs. PMID- 26374623 TI - Outcomes of highly active antiretroviral therapy and its predictors: a cohort study focusing on tuberculosis co-infection in South West Ethiopia. AB - BACKGROUND: In this study, we hypothesized that TB co-infection independently increases the risk of poor treatment outcomes in such patients even if they are on antiretroviral therapy (ART). Therefore, this study was aimed at investigating this hypothesis among cohort of adult PLWHs in South West Ethiopia. METHODOLOGY: Cohort study comparing the immunologic and clinical outcomes of 130 HIV/TB co infected and 520 only HIV patients starting ART was enrolled. Chi square and student t test were used to compare outcome variables and logistic regression was used to assess the effect of TB on treatment failure. RESULTS: In this study, TB co-infection didn't increase immunologic failure even in univariate analysis at both 6 [OR, 1.10 (0.59-1.69), P = 0.85] and 12 months [OR, 1.06 (0.58-1.93), P = 0.89] of ART initiation. However, it increased the risk of clinical failure at both 6 [Adjusted Odd Ratio (AOR), 2.90 (1.41-6.09), P = 0.028] and 12 months [AOR, 2.93 (1.41-6.09), P = 0.004] of ART initiation. CONCLUSION: This study showed that TB co-infection didn't adversely affect the immunologic outcomes, weight and hemoglobin responses even though it increased the risk of clinical failure nearly three times. Therefore, beside the concern given for TB prevention and treatment, several patient and policy related factors need to be addressed to maximally benefit from highly active antiretroviral therapy rollout in resource limited settings. PMID- 26374624 TI - Palliative care and spiritual well-being in lung cancer patients and family caregivers. AB - BACKGROUND: Spiritual well-being is an important dimension of quality of life (QOL) and is a core component of quality oncology and palliative care. In this analysis, we aimed to describe spiritual well-being outcomes in a National Cancer Institute (NCI)-supported Program Project that tested the effectiveness of an interdisciplinary palliative care intervention in lung cancer patients and their family caregivers (FCGs). METHODS: Patients undergoing treatments for NSCLC and their FCGs were enrolled in a prospective, quasi-experimental study. Patients and FCGs in the intervention group were presented at interdisciplinary care meetings and received four educational sessions that included one session focused on spiritual well-being. Spiritual well-being for patients was measured using the FACIT-Sp-12, and FCG spiritual well-being was measured using the COH-QOL-FCG spiritual well-being subscale. Multivariate analysis of covariance was undertaken for subscale and item scores at 12 weeks, controlling for baseline, by religious affiliations (yes or no) and group assignment. RESULTS: Religiously affiliated patients reported better scores in the Faith subscale and items on finding strength and comfort in faith and spiritual beliefs compared to non-affiliated patients. Non-affiliated patients had better scores for feeling a sense of harmony within oneself. By group, patients who received the intervention had significantly better scores for the Meaning/Peace subscale. CONCLUSIONS: Our findings support the multidimensionality of spiritual well-being that includes constructs such as meaning and faith for lung cancer patients and FCGs with or without religious affiliations. Palliative care interventions should include content that targets the spiritual needs of both patients and FCGs. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26374626 TI - Trade-offs in osmoregulation and parallel shifts in molecular function follow ecological transitions to freshwater in the Alewife. AB - Adaptation to freshwater may be expected to reduce performance in seawater because these environments represent opposing selective regimes. We tested for such a trade-off in populations of the Alewife (Alosa pseudoharengus). Alewives are ancestrally anadromous, and multiple populations have been independently restricted to freshwater (landlocked). We conducted salinity challenge experiments, whereby juvenile Alewives from one anadromous and multiple landlocked populations were exposed to freshwater and seawater on acute and acclimation timescales. In response to acute salinity challenge trials, independently derived landlocked populations varied in the degree to which seawater tolerance has been lost. In laboratory-acclimation experiments, landlocked Alewives exhibited improved freshwater tolerance, which was correlated with reductions in seawater tolerance and hypo-osmotic balance, suggesting that trade-offs in osmoregulation may be associated with local adaptation to freshwater. We detected differentiation between life-history forms in the expression of an ion-uptake gene (NHE3), and in gill Na(+) /K(+) -ATPase activity. Trade-offs in osmoregulation, therefore, may be mediated by differentiation in ion-uptake and salt-secreting pathways. PMID- 26374625 TI - Harmonizing Optimal Strategy for Treatment of coronary artery diseases- comparison of REDUCtion of prasugrEl dose or POLYmer TECHnology in ACS patients (HOST-REDUCE-POLYTECH-ACS RCT): study protocol for a randomized controlled trial. AB - BACKGROUND: Antiplatelet treatment is an important component in optimizing the clinical outcomes after percutaneous coronary intervention (PCI) especially in patients with acute coronary syndrome (ACS). Prasugrel, which is a new P2Y12 inhibitor, has been confirmed as efficacious in a large trial in Western countries, and a similar trial is also to be launched in Asian countries. Although a 60-mg loading dose of prasugrel followed by 10 mg per day should be acceptable, there have been no data regarding the optimal dose in Asian patients. Furthermore, serum levels of prasugrel and the rates of platelet inhibition are known to be higher in Asians than Caucasians with the same dose of the drug. Polymer, a key component of drug-eluting stents (DES), has been suggested as the cause of inflammation leading to late complications, and has driven many companies to develop biodegradable-polymer DES. Currently, there are limited data regarding the head-to-head comparison between BP-BES and the biostable polymer CoCr-EES or the newest platinum-chromium everolimus-eluting stent (PtCr-EES). Furthermore, the polymer issue may be more important in ACS where there is ruptured thrombotic plaque where polymer-induced inflammation may affect the local milieu of the stented artery. Therefore, the present study dedicated only to ACS patients, will offer important information on the optimal prasugrel dose in the Asian population by comparing a 10-mg versus a 5-mg maintenance dose beyond 1 month after PCI, as well as giving important insight into the polymer issue by comparing BP-BES versus biostable-polymer PtCr-EES. METHOD/DESIGN: Harmonizing Optimal Strategy for Treatment of coronary artery diseases- comparison of REDUCtion of prasugrEl dose or POLYmer TECHnology in ACS patients (HOST-REDUCE-POLYTECH-ACS) trial is a multicenter, randomized and open-label clinical study with a 2 * 2 factorial design, according to the type of stent (PtCr-EES versus BP-BES) and prasugrel maintenance dose (5 mg versus 10 mg), to demonstrate non-inferiority of PtCr-EES relative to BP-BES or the reduced prasugrel dose relative to conventional dose in an Asian all-comers PCI population presenting with ACS. Approximately 3400 patients will undergo prospective, random assignment separately to either stent or prasugrel arm (1:1 ratio, respectively). When the patients have contraindications to prasugrel, they are categorized into an antiplatelet observation group after stent-randomization. The primary endpoint is the patient-oriented composite outcome, which is a composite of all-cause mortality, any myocardial infarction (MI), any repeat revascularization in the stent arm at 12 months after index PCI. In the prasugrel arm, primary endpoint is any major adverse cardiovascular event, which is a composite of all-cause mortality, any MI, any stent thrombosis (Academic Research Consortium (ARC)-defined), any repeat revascularization, stroke, or bleeding (BARC class >= 2). DISCUSSION: The HOST-REDUCE-POLYTECH-ACS RCT is the first study exploring the optimal maintenance dose of prasugrel beyond 1 month after PCI for ACS in Asian all-comers. In addition, this is the largest study dedicated only to ACS patients to evaluate the polymer issue in the situation of ACS by directly comparing biostable-polymer PtCr-EES versus BP-BES. TRIAL REGISTRATION: ClinicalTrials.gov (ID: NCT02193971, 13 July 2014). PMID- 26374627 TI - Effects of repeated social defeat on adolescent mice on cocaine-induced CPP and self-administration in adulthood: integrity of the blood-brain barrier. AB - Social stress in adulthood enhances cocaine self-administration, an effect that has been related with an increase in extracellular signal-regulated kinase and p38alpha mitogen-activated protein kinase phosphorylation. A detrimental effect of cocaine on blood-brain barrier (BBB) integrity has also been reported. This study evaluates the effects of repeated social defeat (RSD) during adolescence on the reinforcing and motivational effects of cocaine in adult mice and the changes induced by RSD on BBB permeability. Cocaine self-administration, conditioned place preference and quantitative analysis of claudin-5, laminin, collagen-IV and IgG immunoreactivity took place 3 weeks after RSD. Mice socially defeated during adolescence developed conditioned place preference and exhibited reinstated preference with a non-effective dose of cocaine (1 mg/kg). RSD mice needed significantly more sessions than control animals for the preference induced by 25 mg/kg of cocaine to be extinguished. However, acquisition of cocaine self administration (0.5 mg/kg per injection) was delayed in the RSD group. Mice exposed to RSD displayed significant changes in BBB structure in adulthood, with a marked reduction in expression of the tight junction protein claudin-5 and an increase in basal laminin degradation (reflected by a decrease in laminin and collagen-IV expression) in the nucleus accumbens and hippocampus. The detrimental effect induced by cocaine (25 mg/kg) on collagen-IV expression in the hippocampus was more pronounced in RSD mice. In summary, our findings suggest that stress and cocaine can increase the long-term vulnerability of the brain to subsequent environmental insults as a consequence of a sustained disruption of the BBB. PMID- 26374628 TI - Patient reported outcome measures for visual impairment after stroke: a systematic review. AB - PURPOSE: The aim of this review was to identify patient reported outcome measures (PROMs) for use in research and clinical practice involving individuals with visual impairment following stroke and to evaluate their content validity against quality assessment criteria. METHOD: A systematic review of the literature was conducted to identify articles related to the development and/or validation of PROMS. We searched scholarly online resources and hand searched journals. Search terms included MESH terms and alternatives relating to PROMs, visual impairments and quality of life. Data were extracted relating to the development and validation of the included instruments. The quality of the development process was assessed using a modified version of a PROM quality assessment tool. RESULTS: A total of 142 PROMs were identified, 34 vision-specific PROMs were relevant and available to be analysed in this review. Quality appraisal identified four highly rated instruments: the National Eye Institute Visual Functional Questionnaire (NEI-VFQ), Activity Inventory (AI), Daily Living Tasks Dependant on Vision (DLTV) and Veterans Affairs Low Visual Function Questionnaire (VA LV VFQ). The four instruments have only been used with either a limited number of stroke survivors or a sub-population within visual impairment following stroke. CONCLUSION: No instruments were identified which specifically targeted individuals with visual impairment following stroke. Further research is required to identify the items which a population of stroke survivors with visual impairment consider to be of most importance. The validation of a combination of instruments or a new instrument for use with this population is required. PMID- 26374629 TI - Roseovarius aquimarinus sp. nov., a slightly halophilic bacterium isolated from seawater. AB - A Gram-stain-negative, non-spore-forming, rod-shaped, motile, facultatively anaerobic bacterium, designated CAU 1059T, was isolated from a seawater sample from Jeju Island, Republic of Korea. The bacterium grew optimally at 37 degrees C, at pH 7.0 and in the presence of 2 % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain CAU 1059T belonged to the genus Roseovarius. It exhibited only 91.5-96.9 % sequence similarity to the type strains of recognized Roseovarius species. Similar to other species of the genus Roseovarius, strain CAU 1059T had ubiquinone-10 (Q-10) as the predominant ubiquinone and C16 : 0 and summed feature 8 (C18 : 1omega7c/omega6c) as the major fatty acids. The polar lipid pattern consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and phosphatidylcholine; three unidentified phospholipids, two aminolipids, an aminophospholipid and nine other lipids were also found. The G+C content of the genomic DNA was 61.9 mol%. On the basis of the data provided, strain CAU 1059T should be classified as representing a novel species of the genus Roseovarius, for which the name Roseovarius aquimarinus sp. nov. is proposed. The type strain is CAU 1059T ( = KCTC 32014T = CCUG 64792T). PMID- 26374631 TI - Erratum to: Experiences of healing therapy in patients with irritable bowel syndrome and inflammatory bowel disease. PMID- 26374630 TI - Distribution of alpha-synuclein in the spinal cord and dorsal root ganglia in an autopsy cohort of elderly persons. AB - BACKGROUND: Lewy body-related alpha-synucleinopathy (LBAS, the abnormal accumulation of pathologic alpha-synuclein) is found in the central and peripheral nervous systems, including the spinal cord, dorsal root ganglia, and sympathetic ganglia, of Parkinson's disease patients. However, few studies have focused on the distribution of LBAS in the spinal cord, primary sensory neurons, and preganglionic sympathetic nerves. RESULTS: We analyzed 265 consecutive subjects with LBAS who underwent autopsy at a general geriatric hospital. LBAS in the spinal cord was significantly associated with that in the lower brainstem regions that are directly connected to the spinal cord (i.e., the medullary reticular formation and locus ceruleus), but it was not associated with the olfactory bulb-amygdala system, which is not directly connected to the spinal cord, suggesting that the lower brainstem is a key structure regarding the spread of LBAS to the spinal cord. In the primary sensory neurons, most subjects with LBAS in the dorsal root ganglia had LBAS in the dorsal root, and all subjects with LBAS in the dorsal root also had LBAS in the dorsal horn, suggesting that LBAS spreads retrogradely from the axonal terminals of the dorsal horn to the somata of the dorsal root ganglia via the dorsal root. In the preganglionic sympathetic nerves, the LBAS in the sympathetic ganglia preceded that in the nucleus of the intermediolateral column of the thoracic cord, suggesting that LBAS spreads retrogradely through the preganglionic sympathetic nerves. CONCLUSIONS: LBAS in the spinal cord was associated with the lower regions of the brainstem, but not with the olfactory bulb or amygdala. LBAS may spread centrifugally along the primary sensory neurons, whereas it may spread centripetally along the preganglionic sympathetic nerves. PMID- 26374632 TI - PML-RARa modulates the vascular signature of extracellular vesicles released by acute promyelocytic leukemia cells. AB - Oncogenic transformation is believed to impact the vascular phenotype and microenvironment in cancer, at least in part, through mechanisms involving extracellular vesicles (EVs). We explored these questions in the context of acute promyelocytic leukemia cells (NB4) expressing oncogenic fusion protein, PML-RARa and exquisitely sensitive to its clinically used antagonist, the all-trans retinoic acid (ATRA). We report that NB4 cells produce considerable numbers of EVs, which are readily taken up by cultured endothelial cells triggering their increased survival. NB4 EVs contain PML-RARa transcript, but no detectable protein, which is also absent in endothelial cells upon the vesicle uptake, thereby precluding an active intercellular trafficking of this oncogene in this setting. ATRA treatment changes the emission profile of NB4-related EVs resulting in preponderance of smaller vesicles, an effect that occurs in parallel with the onset of cellular differentiation. ATRA also increases IL-8 mRNA and protein content in NB4 cells and their EVs, while decreasing the levels of VEGF and tissue factor (TF). Endothelial cell uptake of NB4-derived EVs renders these cells more TF-positive and procoagulant, and this effect is diminished by pre treatment of EV donor cells with ATRA. Profiling angiogenesis-related transcripts in intact and ATRA-treated APL cells and their EVs reveals multiple differences attributable to cellular responses and EV molecular packaging. These observations point to the potential significance of changes in the angiogenic signature and activity associated with EVs released from tumor cells subjected to targeted therapy. PMID- 26374633 TI - Repurposing some older drugs that cross the blood-brain barrier and have potential anticancer activity to provide new treatment options for glioblastoma. AB - Glioblastoma is a brain neoplasm with limited 5-year survival rates. Developments of new treatment regimens that improve patient survival in patients with glioblastoma are needed. It is likely that a number of existing drugs used in other conditions have potential anticancer effects that offer significant survival benefit to glioblastoma patients. Identification of such drugs could provide a novel treatment paradigm. PMID- 26374635 TI - Effects of eccentric-focused and conventional resistance training on strength and functional capacity of older adults. AB - The aim of the study was to assess the effect of eccentric training using a constant load with longer exposure time at the eccentric phase on knee extensor muscle strength and functional capacity of elderly subjects in comparison with a conventional resistance training program. Twenty-six healthy elderly women (age = 67 +/- 6 years) were randomly assigned to an eccentric-focused training group (ETG; n = 13) or a conventional training group (CTG; n = 13). Subjects underwent 12 weeks of resistance training twice a week. For the ETG, concentric and eccentric phases were performed using 1.5 and 4.5 s, respectively, while for CTG, each phase lasted 1.5 s. Maximum dynamic strength was assessed by the one repetition maximum (1RM) test in the leg press and knee extension exercises, and for functional capacity, subjects performed specific tests (6-m walk test, timed up-and-go test, stair-climbing test, and chair-rising test). Both groups improved knee extension 1RM (24-26 %; p = 0.021), timed up-and-go test (11-16 %; p < 0.001), 6-m walk test (9-12 %; p = 0.004), stair-climbing test (8-13 %; p = 0.007), and chair-rising test (15-16 %; p < 0.001), but there was no significant difference between groups. In conclusion, the strategy of increasing the exposure time at the eccentric phase of movement using the same training volume and intensity does not promote different adaptations in strength or functional capacity compared to conventional resistance training in elderly woman. PMID- 26374636 TI - Extensive fitness and human cooperation. AB - Evolution depends on the fitness of organisms, the expected rate of reproducing. Directly getting offspring is the most basic form of fitness, but fitness can also be increased indirectly by helping genetically related individuals (such as kin) to increase their fitness. The combined effect is known as inclusive fitness. Here it is argued that a further elaboration of fitness has evolved, particularly in humans. It is called extensive fitness and it incorporates producing organisms that are merely similar in phenotype. The evolvability of this mechanism is illustrated by computations on a simple model combining heredity and behaviour. Phenotypes are driven into the direction of high fitness through a mechanism that involves an internal estimate of fitness, implicitly made within the organism itself. This mechanism has recently been conjectured to be responsible for producing agency and goals. In the model, inclusive and extensive fitness are both implemented by letting fitness increase nonlinearly with the size of subpopulations of similar heredity (for the indirect part of inclusive fitness) and of similar phenotype (for the phenotypic part of extensive fitness). Populations implementing extensive fitness outcompete populations implementing mere inclusive fitness. This occurs because groups with similar phenotype tend to be larger than groups with similar heredity, and fitness increases more when groups are larger. Extensive fitness has two components, a direct component where individuals compete in inducing others to become like them and an indirect component where individuals cooperate and help others who are already similar to them. PMID- 26374634 TI - A protocol for the identification and validation of novel genetic causes of kidney disease. AB - BACKGROUND: Genetic renal diseases (GRD) are a heterogeneous and incompletely understood group of disorders accounting for approximately 10 % of those diagnosed with kidney disease. The advent of Next Generation sequencing and new approaches to disease modelling may allow the identification and validation of novel genetic variants in patients with previously incompletely explained or understood GRD. METHODS/DESIGN: This study will recruit participants in families/trios from a multidisciplinary sub-specialty Renal Genetics Clinic where known genetic causes of GRD have been excluded or where genetic testing is not available. After informed patient consent, whole exome and/or genome sequencing will be performed with bioinformatics analysis undertaken using a customised variant assessment tool. A rigorous process for participant data management will be undertaken. Novel genetic findings will be validated using patient-derived induced pluripotent stem cells via differentiation to renal and relevant extra renal tissue phenotypes in vitro. A process for managing the risk of incidental findings and the return of study results to participants has been developed. DISCUSSION: This investigator-initiated approach brings together experts in nephrology, clinical and molecular genetics, pathology and developmental biology to discover and validate novel genetic causes for patients in Australia affected by GRD without a known genetic aetiology or pathobiology. PMID- 26374637 TI - Treatment estimates of unsafe pregnancy termination complications: a catalyst for change. PMID- 26374638 TI - Genetic variation and population structure of American mink Neovison vison from PCB-contaminated and non-contaminated locales in eastern North America. AB - American mink Neovison vison may be particularly vulnerable to toxicities of persistent contaminants such as PCBs because of their aquatic-based diet, position near the top of the food web, and small deme sizes. Furthermore, ranched mink are sensitive to reproductive toxicities of fish diets from PCB-polluted sites. The upper Hudson River is highly contaminated with PCBs and previous studies have shown elevated hepatic burdens of total and coplanar PCBs in mink collected near the river compared with those from more distant locales in New York and elsewhere. We hypothesized that bioaccumulation of PCBs in Hudson River mink has reduced their levels of genetic diversity or altered their genetic population structure. To address this, we conducted microsatellite DNA analysis on collections made in proximity to and from more distant locales in the Hudson River watershed, elsewhere in New York State, and at other sites in eastern North America including New Brunswick, four locales in Ontario, multiple drainages in Maine, and two ecoregions in Rhode Island. We did not find reduced genetic diversity at the individual or population levels in mink collected near (<6 km) to PCB hotspots in the Hudson River nor evidence of altered population structure. Consistent with their distribution in small localized and isolated demes, we did find significant genetic population structure among many mink collections in New York State and elsewhere. Depending on the analytical approach used, genetically distinct populations numbered between 16 when using STRUCTURE to 19-20 when using Exact G tests, F ST, or AMOVA analyses. Genetically distinct population units were found among major ecoregions and minor ecoregions in New York State, among different hydrologic subunits within the Hudson River watershed, among spatially separate locales in Ontario, and among most watersheds in Maine. However, despite this localization and potential heightened impact of stressors, genetic diversity and genetic population structure in mink does not seem to be affected by their bioaccumulation of high levels of PCBs of Hudson River origin. PMID- 26374639 TI - Systemic air embolism causing acute stroke and myocardial infarction after percutaneous transthoracic lung biopsy-a case report. AB - Computed tomography (CT)-guided transthoracic lung biopsy is a common procedure for the diagnosis of pulmonary lesion. Pneumothorax, pulmonary hemorrhage and hemoptysis are the most common complications of the procedure. Air embolism is a rare serious complication. We reported a case with air embolism related acute ischemic stroke and non-ST elevation myocardial infarction (NSTEMI) simultaneously after percutaneous transthoracic lung biopsy. PMID- 26374641 TI - A weighting approach for judging the effect of patient strata on high-dimensional risk prediction signatures. AB - BACKGROUND: High-dimensional molecular measurements, e.g. gene expression data, can be linked to clinical time-to-event endpoints by Cox regression models and regularized estimation approaches, such as componentwise boosting, and can incorporate a large number of covariates as well as provide variable selection. If there is heterogeneity due to known patient subgroups, a stratified Cox model allows for separate baseline hazards in each subgroup. Variable selection will still depend on the relative stratum sizes in the data, which might be a convenience sample and not representative for future applications. Such effects need to be systematically investigated and could even help to more reliably identify components of risk prediction signatures. RESULTS: Correspondingly, we propose a weighted regression approach based on componentwise likelihood-based boosting which is implemented in the R package CoxBoost (https://github.com/binderh/CoxBoost). This approach focuses on building a risk prediction signature for a specific stratum by down-weighting the observations from the other strata using a range of weights. Stability of selection for specific covariates as a function of the weights is investigated by resampling inclusion frequencies, and two types of corresponding visualizations are suggested. This is illustrated for two applications with methylation and gene expression measurements from cancer patients. CONCLUSION: The proposed approach is meant to point out components of risk prediction signatures that are specific to the stratum of interest and components that are also important to other strata. Performance is mostly improved by incorporating down-weighted information from the other strata. This suggests more general usefulness for risk prediction signature development in data with heterogeneity due to known subgroups. PMID- 26374640 TI - Recent Progress in the Understanding of Obesity: Contributions of Genome-Wide Association Studies. AB - Since 2007, discovery of genetic variants associated with general obesity and fat distribution has advanced tremendously through genome-wide association studies (GWAS). Currently, the number of robustly associated loci is 190. Even though these loci explain <3 % of the variance, they have provided us a still emerging picture of genomic localization, frequency and effect size spectra, and hints of functional implications. The translation into biological knowledge has turned out to be an immense task. However, in silico enrichment analyses of genes involved in specific pathways or expressed in specific tissues have the power to suggest biological mechanisms underlying obesity. Inspired by this, we highlight genes in five loci potentially mechanistically linked to leptin-receptor trafficking and signaling in primary cilia. The clinical application of genetic knowledge as prediction, prevention, or treatment strategies is unfortunately still far from reality. Thus, despite major advances, further research is warranted to solve one of the greatest health problems in modern society. PMID- 26374642 TI - Proteomic analysis of O-GlcNAcylated proteins in invasive ductal breast carcinomas with and without lymph node metastasis. AB - The potential role of protein O-GlcNAcylation in cancer has been studied extensively, and the spread of cancer cells to regional lymph nodes is the first step in the dissemination of breast cancer. However, the correlation between O GlcNAcylation and lymphatic metastasis in breast cancer remains elusive. In this study, we demonstrated that the overall O-GlcNAcylation as well as O-GlcNAc transferase (OGT) tends to decrease in response to the augmentation of lymph node metastasis (LNM) in invasive ductal breast carcinomas (IDCs). Although accumulating evidence indicates that individual O-GlcNAcylation may be important in the pathogenesis of breast cancer, O-GlcNAcylated proteins in IDCs are still largely unexplored. Herein, O-GlcNAcylated proteins of IDCs were chemo enzymatically enriched and identified via liquid chromatography combined with tandem mass spectrometry. In total, 155 O-GlcNAcylated proteins were determined, of which 41 were only observed in LNM tissues, while 40 were unique in non-LNM samples. Gene ontology analysis showed that O-GlcNAc is primarily a nucleocytoplasmic post-translational modification, and most enriched functional terms were related to cancer development in both metastatic and non-metastatic IDCs. Moreover, several O-GlcNAcylated proteins involved in glycolysis and its accessory pathway were identified from LNM and non-LNM groups, respectively. These results indicate that the O-GlcNAcylation statuses of individual proteins were independent of the overall O-GlcNAcylation levels of metastatic and non metastatic IDCs. Aberrant O-GlcNAc modification of these proteins might be associated with LNM progression. PMID- 26374643 TI - Amino acids and autophagy: their crosstalk, interplay and interlock. PMID- 26374644 TI - New perineal injection technique for pudendal nerve infiltration in diagnostic and therapeutic procedures. AB - PURPOSE: Pudendal nerve injection is used as a diagnostic procedure in the vulvar region and for therapeutic purposes, such as in vulvodynia. Here, we provide a new, easy-to-perform perineal injection technique. PATIENTS AND METHODS: We analyzed 105 perineal injections into the pudendal nerve with a local anesthetic (LA), procaine in 20 patients. A 0.4 * 40 mm needle was handled using a stop-and go technique while monitoring the patient's discomfort. The needle was placed 1-2 cm laterally to the dorsal introitus. After aspiration, a small amount of LA was applied. After subcutaneous anesthesia, the needle was further advanced step-by step. Thus, 5 ml could be applied with little discomfort to the patient. Anesthesia in the pudendal target region was the primary endpoint of our analysis. RESULTS: In 93 of 105 injections (88.6 %), complete perineal anesthesia was achieved with a single injection. 12 injections were repeated. These injections were excluded from the analysis. Severity of injection pain, on visual analog scale (VAS) from 0 to 100, was 26.8 (95 % CI 7.2-46.4). Age (beta = 0.33, p < 0.01) and the number of previous injections (beta = 0.35, p < 0.01) inversely correlated with injection pain. Injection pain and anesthesia were not affected by BMI, the number and the side of previous injections, or order of injection. A reversible vasovagal reaction was common, but no serious adverse effects occurred. CONCLUSION: Perineal pudendal injection is an effective and safe technique for anesthesia in diagnostic (vulva biopsy) and therapeutic indications (pudendal neuralgia), and regional anesthesia in perinatal settings. PMID- 26374645 TI - The association between fetal head position prior to vacuum extraction and pregnancy outcome. AB - OBJECTIVE: To estimate the association of fetal head position prior to vacuum extraction (VE) and pregnancy outcome. STUDY DESIGN: A retrospective cohort study of singleton pregnancies who underwent VE. Pregnancy outcome of occipito-anterior (OA) position of the fetal head was compared to those with occipito-posterior (OP) position. RESULTS: Amongst overall 12,063 women undergoing trial of labor, there were 1118 (9.2%) VE deliveries. Of them, 871 (77.9%) had OA and 247 (22.1%) had OP position of the fetal head. Except for a higher rate of nulliparity in the OA group, no significant differences between the groups regarding pregnancy complications and birthweight were noted. In the OP group, there were higher rates of prolonged 2nd-stage of labor as an indication for VE (49.8 vs. 36.5%, p < 0.001) and single detachment of vacuum cup (11.3 vs. 6.7%, p = 0.02) without any increased risk of failed extraction. Higher risks for sub-galeal hematoma (aOR = 4.36, p = 0.03) and low 5-min Apgar score (aOR = 4.63, p = 0.02) were observed in the OP group with otherwise similar rates of adverse maternal and neonatal outcomes. CONCLUSION: Among women undergoing VE, OP position is associated with higher rate of vacuum cup detachment, low 5-min Apgar score and increased risk for sub-galeal hematoma with otherwise similar rates of adverse maternal and neonatal outcomes. PMID- 26374646 TI - Analysis of differentially expressed genes between endometrial carcinosarcomas and endometrioid endometrial carcinoma by bioinformatics. AB - PURPOSE: This study aimed to explore the underlying molecular mechanisms of endometrial carcinosarcomas (ECS) and endometrioid endometrial carcinoma (EEC) by bioinformatics analysis. METHODS: Gene expression profile GSE33723 was downloaded from the Gene Expression Omnibus. A total of 15 ECS and 23 EEC samples were used to identify the differentially expressed genes (DEGs) by significance analysis of microarrays. After construction of protein-protein interaction (PPI) network, Gene Ontology (GO) functional and pathway enrichment analyses of DEGs were performed, followed by network module analysis. RESULTS: A total of 49 DEGs were identified between EEC and ECS samples. In the PPI network, TP53 (tumor protein p53) was selected as the highest degree, hub centrality and betweenness. The top 10 enriched GO terms including regulation of cell death and top 10 significant pathways including cell cycle were selected. After network module analysis, PIK3R1 (phosphoinositide-3-kinase, regulatory subunit 1) and AKT2 (v-akt murine thymoma viral oncogene homolog 2) were selected as the co-expressed genes in the states of ECS while STAT3 (signal transducer and activator of transcription 3) and JAZF (JAZF zinc finger 1) were selected as the co-expressed genes in the states of EEC. CONCLUSIONS: The DEGs, such as TP53, PIK3R1 and AKT2 may be used for targeted diagnosis and treatment of ECS while STAT3 and JAZF1 may be served as a target for EEC. PMID- 26374647 TI - [Patient blood management: Current state of the literature]. AB - BACKGROUND: Preoperative anemia has a prevalence of approximately 30% and is one of the strongest predictors of perioperative red blood cell (RBC) transfusion. It is rarely treated although it is an independent risk factor for the occurrence of postoperative complications. Additionally, the high variability in the worldwide usage of RBC transfusions is alarming. Due to these serious deficits in patient care, in 2011 the World Health Organization recommended the implementation of a patient blood management (PBM). OBJECTIVES: This article provides information about PBM as a multidimensional and interdisciplinary approach. MATERIAL AND METHODS: A selective literature search was carried out in the Medline and Cochrane library databases including consideration of national and international guidelines. RESULTS: A PBM promotes the medically and ethically appropriate use of all available resources, techniques and materials in favor of an optimized perioperative patient care. Patients' own resources should be specifically protected, strengthened and used and include (i) diagnosis and therapy of preoperative anemia, (ii) minimizing perioperative blood loss, (iii) blood conserving surgical techniques, (iv) restriction of diagnostic blood sampling, (v) utilization of individual anemia tolerance, (vi) optimal coagulation and hemotherapy concepts and (vii) guideline-based, rational indications for the use of RBC transfusions. CONCLUSION: A PBM should be advocated as an incentive to evaluate and critically optimize local conditions. An individual, interdisciplinarily structured bundle of different PBM measures has great potential to optimize the quality of patient care and to make it safer. PMID- 26374648 TI - [Evaluation of interest in research among surgically active medical officers in the German Armed Forces]. AB - BACKGROUND: Research in military medicine and in particular combat surgery is a broad field that has gained international importance during the last decade. In the context of increased NATO missions, this also holds true for the Bundeswehr (German Armed Forces); however, medical officers in surgery must balance research between their clinical work load, missions, civilian and family obligation. MATERIAL AND METHODS: To evaluate engagement with and interest in research, a questionnaire was distributed among the doctors of the surgical departments of the Bundeswehr hospitals by the newly founded working group Chirurgische Forschung der Bundeswehr (surgical research of the Bundeswehr). Returned data were recorded from October 2013 to January 2014 and descriptive statistics were performed. RESULTS: Answers were received from 87 out of 193 military surgeons (45 %). Of these 81 % announced a general interest in research with a predominance on clinical research in preference to experimental settings. At the time of the evaluation 32 % of the participants were actively involved in research and 53 % regarded it as difficult to invest time in research activities parallel to clinical work. Potential keys to increase the interest and engagement in research were seen in the implementation of research coordinators and also in a higher amount of free time, for example by research rotation. CONCLUSION: Research can be regarded as having a firm place in the daily work of medical officers in the surgical departments of the Bundeswehr; however, the engagement is limited by time and structural factors. At the departmental level and in the command structures of the military medical service, more efforts are recommended in the future in order to enhance the engagement with surgical research. This evaluation should be repeated in the coming years as a measuring instrument and data should be compared in an international context. PMID- 26374649 TI - [Intermittent ishemia of the left leg after gunshot injury to the thorax]. PMID- 26374650 TI - [Are there too many conferences for general and visceral surgery in Germany? : A survey of DGAV members]. AB - BACKGROUND: Human and financial resources are increasingly bound due to economic pressure and the working hours Act whereby the already restricted further training times are further limited. The industry also has less funding available for sponsorship of conferences and workshops. Against this background the question arises whether a reduction or focusing of the conferences is necessary; therefore, the aim of this survey was to obtain an opinion from members of the German Society of General and Visceral Surgery (DGAV) and possibly to derive a need for action to submit to the board members. METHODS: From 7 February to 18 March 2015 an online survey was conducted by the DGAV with their members regarding the number of necessary congress events in Germany. RESULTS: A total of 670 responses were received (return rate 16 %). In total, 56 % of participants felt that there are too many conferences. A differentiation according to the position of the respondent and the level of the associated hospital resulted in the following: 69.3 % of the participating head physicians (HP) shared this opinion, compared to 48.6 % of senior physicians (SP) and 34.4 % of residents (RP). Of the participants from basic and standard care hospitals (B/SC) 50 % shared this opinion, compared to 59.2 % from maximum care hospitals (MC) and 63.6 % from university hospitals (UH). In addition, a total of 75 % of the participants (HP 82.9 %, SP 78.4 %, RP 70.5 %) were in favor of keeping the congress of the DGAV (annual meeting of the German Society for Digestive and Metabolic Diseases in conjunction with the Autumn meeting of the DGAV) in its previous form, regardless of the underlying level of care of the associated hospital (B/SC 77 %, MC 79 %, UC 68 %). CONCLUSION: More experienced surgeons in particular tended to favor a reduction of events with a focus on the major conferences; however, younger colleagues preferred a wider spectrum of meetings. In order to comply with both positions a wide range of events should be continued to be provided in the future so that surgeons can choose which to attend according to the individual preferences. PMID- 26374651 TI - [Neoadjuvant therapy for tumors of the upper gastrointestinal tract : Complication management]. AB - Recent studies could demonstrate that neoadjuvant chemotherapy and radiochemotherapy for esophageal and gastric cancer do not significantly increase the risk of postoperative morbidity and mortality as compared to surgery alone. With respect to patient safety and effectiveness of neoadjuvant concepts, quality assured performance of each treatment modality and close interdisciplinary cooperation play an important role. The majority of potential side effects and complications, which might occur during neoadjuvant therapy can be adequately controlled by correct prophylaxis and professional medical complication management. Complications before, during and after neoadjuvant therapy of upper gastrointestinal tract tumors can also be caused by the tumor itself or by medicinal therapy. These comprise bleeding, fistulas, perforations and stenoses. Modern endoscopic techniques are the therapy of choice in these situations. Preoperative conditioning during the period of neoadjuvant therapy opens the possibility of reduced postoperative complications to patients with tumors of the upper gastrointestinal tract. PMID- 26374652 TI - Identification of Potential PPAR gamma Agonists as Hypoglycemic Agents: Molecular Docking Approach. AB - Peroxisome proliferator-activated receptor gamma (PPAR gamma) has become an attractive molecular target for drugs that aim to treat hyperglycemia. The object of our study is to identify the required molecular descriptor and essential amino acid residues for effective PPAR gamma agonistic activity. In this work, we employed Molegro Virtual Docker program in all molecular docking simulations. Accuracy of receptor-compound docking was validated on a set of 15 PPAR gamma compound complexes for which crystallographic structures were available. The reliability of the docking results was acceptable with good root-mean-square deviation value (<2 A). A significant correlation between different data derived from docking calculations and experimental data was revealed. Our results allowed identification of compounds with potential to become drugs against hyperglycemia. PMID- 26374653 TI - Protective Effect of Sundakai (Solanum torvum) Seed Protein (SP) Against Oxidative Membrane Damage in Human Erythrocytes. AB - Lipid peroxidation by ROS at the membrane level disturbs the inherit integrity of components activating subsequent alterations in the function. In this study, the protective effect of purified Sundakai (Solanum torvum) seed protein (SP) was tested against oxidative membrane damage in erythrocyte membrane. SP prevented oxidative RBC lysis induced by pro-oxidants; Fe:As (2:20 MUmol), periodate (0.4 mM), and t-BOOH (1 mM) up to 86, 81, and 86 %, respectively. Further, SP prevented the Fe:As-induced K(+) leakage up to the tune of 95 %. The inhibition offered by SP on K(+) leakage was comparable to inhibition offered by quinine sulfate, a known K(+) channel blocker. SP dose dependently restored Na(+)K(+) ATPase and Ca(2+)Mg(2+) ATPase activities in erythrocyte membrane. The restoration of ATPase activity by SP was two times more than standard antioxidants BHA and alpha-tocopherol. Besides, SP at 1.6 MUmol restored the membrane proteins over Fe:As induction when analyzed by SDS-PAGE, which was comparable to protection offered by BHA. In conclusion, SP is an effective antioxidant in preventing oxidative membrane damage and associated functions mediated by ROS. As SP is non-toxic, it can be used as an effective bioprotective antioxidant agent to cellular components. PMID- 26374654 TI - Alternatives to Incomplete Colonoscopy. AB - A thorough and complete colonoscopy is critically important in preventing colorectal cancer. Factors associated with difficult and incomplete colonoscopy include a poor bowel preparation, severe diverticulosis, redundant colon, looping, adhesions, young and female patients, patient discomfort, and the expertise of the endoscopist. For difficult colonoscopy, focusing on bowel preparation techniques, appropriate sedation and adjunct techniques such as water immersion, abdominal pressure techniques, and patient positioning can overcome many of these challenges. Occasionally, these fail and other alternatives to incomplete colonoscopy have to be considered. If patients have low risk of polyps, then noninvasive imaging options such as computed tomography (CT) or magnetic resonance (MR) colonography can be considered. Novel applications such as Colon CapsuleTM and Check-Cap are also emerging. In patients in whom a clinically significant lesion is noted on a noninvasive imaging test or if they are at a higher risk of having polyps, balloon-assisted colonoscopy can be performed with either a single- or double-balloon enteroscope or colonoscope. The application of these techniques enables complete colonoscopic examination in the vast majority of patients. PMID- 26374655 TI - Assessment of exposures and potential risks to the US adult population from the leaching of elements from gold and ceramic dental restorations. AB - Using data from the 2001 to 2004 US National Health and Nutrition Examination Survey (NHANES) on the number and placement of tooth restorations in adults, we quantified daily doses due to leaching of elements from gold (Au) alloy and ceramic restorative materials. The elements with the greatest leaching rates from these materials are often the elements of lowest proportional composition. As a result, exposure due to wear will predominate for those elements of relatively high proportional composition, while exposure due leaching may predominate for elements of relatively low proportional composition. The exposure due to leaching of silver (Ag) and palladium (Pd) from Au alloys exceeded published reference exposure levels (RELs) for these elements when multiple full surface crowns were present. Six or more molar crowns would result in exceeding the REL for Ag, whereas three or more crowns would be necessary to exceed the REL for Pd. For platinum (Pt), the majority of tooth surfaces, beyond just molar crowns, would be necessary to exceed the REL for Pd. Exposures due to leaching of elements from ceramic dental materials were less than published RELs for all components examined here, including having all restorations composed of ceramic. PMID- 26374657 TI - A weight-of-evidence approach to identify nanomaterials in consumer products: a case study of nanoparticles in commercial sunscreens. AB - Nanoscale ingredients in commercial products represent a point of emerging environmental concern due to recent findings that correlate toxicity with small particle size. A weight-of-evidence (WOE) approach based upon multiple lines of evidence (LOE) is developed here to assess nanomaterials as they exist in consumer product formulations, providing a qualitative assessment regarding the presence of nanomaterials, along with a baseline estimate of nanoparticle concentration if nanomaterials do exist. Electron microscopy, analytical separations, and X-ray detection methods were used to identify and characterize nanomaterials in sunscreen formulations. The WOE/LOE approach as applied to four commercial sunscreen products indicated that all four contained at least 10% dispersed primary particles having at least one dimension <100 nm in size. Analytical analyses confirmed that these constituents were comprised of zinc oxide (ZnO) or titanium dioxide (TiO2). The screening approaches developed herein offer a streamlined, facile means to identify potentially hazardous nanomaterial constituents with minimal abrasive processing of the raw material. PMID- 26374656 TI - Urinary biomarker concentrations of captan, chlormequat, chlorpyrifos and cypermethrin in UK adults and children living near agricultural land. AB - There is limited information on the exposure to pesticides experienced by UK residents living near agricultural land. This study aimed to investigate their pesticide exposure in relation to spray events. Farmers treating crops with captan, chlormequat, chlorpyrifos or cypermethrin provided spray event information. Adults and children residing <=100 m from sprayed fields provided first-morning void urine samples during and outwith the spray season. Selected samples (1-2 days after a spray event and at other times (background samples)) were analysed and creatinine adjusted. Generalised Linear Mixed Models were used to investigate if urinary biomarkers of these pesticides were elevated after spray events. The final data set for statistical analysis contained 1518 urine samples from 140 participants, consisting of 523 spray event and 995 background samples which were analysed for pesticide urinary biomarkers. For captan and cypermethrin, the proportion of values below the limit of detection was greater than 80%, with no difference between spray event and background samples. For chlormequat and chlorpyrifos, the geometric mean urinary biomarker concentrations following spray events were 15.4 MUg/g creatinine and 2.5 MUg/g creatinine, respectively, compared with 16.5 MUg/g creatinine and 3.0 MUg/g creatinine for background samples within the spraying season. Outwith the spraying season, concentrations for chlorpyrifos were the same as those within spraying season backgrounds, but for chlormequat, lower concentrations were observed outwith the spraying season (12.3 MUg/g creatinine). Overall, we observed no evidence indicative of additional urinary pesticide biomarker excretion as a result of spray events, suggesting that sources other than local spraying are responsible for the relatively low urinary pesticide biomarkers detected in the study population. PMID- 26374658 TI - Contact sensitivity to topical corticosteroids in India. PMID- 26374659 TI - Dermatophytoma: An under-recognized condition. PMID- 26374662 TI - Health-Related Utility Weights in a Cohort of Real-World Crohn's Disease Patients. AB - BACKGROUND AND AIMS: Estimating health-related utility weights in Crohn's Disease [CD] patients is crucial for assessing the cost-effectiveness of new pharmaceutical interventions. Values used in most analyses are based on secondary data and vary substantially among studies. We estimated utility weights in a consecutive sample of real-world CD patients. METHODS: Patients enrolled in an ongoing socioeconomic study of CD in the Israeli adult patient population completed a self-administered Short Form 36 health survey [SF-36] and Short Inflammatory Bowel Disease [SIBDQ] questionnaires and were assessed for their current clinical status, including the Harvey-Bradshaw Index [HBI] of disease severity. For each patient enrolled we calculated a utility weight using the SF 6D scoring system. RESULTS: The cohort comprised 425 patients [40% male] with mean age of 39.1 [+/- 14.0] years. The average HBI was 6.1 [+/- 5.4]; 198 [47%] patients were in remission state [HBI < 5], 99 [23%] had mild disease [HBI 5-7], 102 [25%] moderate [HBI 8-16], and 26 [6%] severe disease [HBI > 16]. Mean utility weights were: 0.667 in all patients, 0.744 in patients with disease remission, 0.638 in mild disease, 0.587 in moderate disease, and 0.505 in severe disease. The significant predictors of utility weights in a multivariable regression analysis were the HBI [beta = -0.494; p < 0.001], economic status [beta = 0.198; p < 0.001], time since diagnosis [beta = 0.106; p < 0.001], male [compared with female] gender [beta = 0.099; p = 0.009], hospital admission in the past year for any cause [beta = -0.086; p = 0.027], and treatment with steroids [beta = -0.100; p = 0.012] where beta denotes the standardised regression coefficients; model adjusted R(2) = 0.428. CONCLUSIONS: Utility weights for patients in the remission and mild disease states were generally lower as compared with values used in published cost-effectiveness analyses. These values should be considered when assessing the value for money of future interventions for CD. PMID- 26374663 TI - Clinical Features of Tuberculous Versus Crohn's Anal Fistulas, in Korea. AB - BACKGROUND AND AIMS: In Western countries, tuberculous anal fistula may not be an issue because tuberculosis [TB] is not common, and this is a very rare form of extrapulmonary manifestation of TB. However in TB-endemic countries, careful diagnostic differentiation is required because the clinical features of TB anal fistula and Crohn's disease [CD] anal fistula are similar, with distinguishing features remaining unclear. We aimed to analyse the clinical features of TB versus CD anal fistulas. METHOD: Among 13872 patients who underwent anal fistula surgery from 2003 to 2014, 87 patients with TB fistulas and 116 patients with CD fistulas were included. Data on the annual incidence of TB and CD, as well as the clinical, pathological, ultrasonographic, colonoscopic and surgical data were analysed. RESULTS: Compared with CD, the TB group was older [median: 37 vs 22 years] and underlying chronic illness was more common [20.3% vs 2.6%]. In the TB group, 46 patients [59.7%] showed active or inactive pulmonary TB, and acid-fast bacilli and caseating granuloma were found in 56.3% and 62.1%, respectively. During colonoscopy, mucosal lesions were observed more frequently in CD [96.9% vs 16.9%]. CONCLUSIONS: TB anal fistula is clinically very similar to CD anal fistula. In Korea, the incidence of CD anal fistula has recently increased in prevalence, whereas the prevalence of TB anal fistula is decreasing but is still persistent. We recommend that clinicians should prepare for a possibility of TB as well as CD anal fistula in TB-endemic countries including Korea. PMID- 26374664 TI - Comment on Intestinal Cavernous Haemangioma and Ulcerative Colitis--Coincidence or Association? PMID- 26374666 TI - Phylogeography, historical demography and habitat suitability modelling of freshwater fishes inhabiting seasonally fluctuating Mediterranean river systems: a case study using the Iberian cyprinid Squalius valentinus. PMID- 26374665 TI - Transcription in space--environmental vs. genetic effects on differential immune gene expression. AB - Understanding how organisms adapt to their local environment is one of the key goals in molecular ecology. Adaptation can be achieved through qualitative changes in the coding sequence and/or quantitative changes in gene expression, where the optimal dosage of a gene's product in a given environment is being selected for. Differences in gene expression among populations inhabiting distinct environments can be suggestive of locally adapted gene regulation and have thus been studied in different species (Whitehead & Crawford ; Hodgins-Davis & Townsend ). However, in contrast to a gene's coding sequence, its expression level at a given point in time may depend on various factors, including the current environment. Although critical for understanding the extent of local adaptation, it is usually difficult to disentangle the heritable differences in gene regulation from environmental effects. In this issue of Molecular Ecology, Stutz et al. () describe an experiment in which they reciprocally transplanted three-spined sticklebacks (Gasterosteus aculeatus) between independent pairs of small and large lakes. Their experimental design allows them to attribute differences in gene expression among sticklebacks either to lake of origin or destination lake. Interestingly, they find that translocated sticklebacks show a pattern of gene expression more similar to individuals from the destination lake than to individuals from the lake of origin, suggesting that expression of the targeted genes is more strongly regulated by environmental effects than by genetics. The environmental effect by itself is not entirely surprising; however, the relative extent of it is. Especially when put in the context of local adaptation and population differentiation, as done here, these findings cast a new light onto the heritability of differential gene expression and specifically its relative importance during population divergence and ultimately ecological speciation. PMID- 26374667 TI - Basiliximab treatment for autoimmune bowel disease in a pediatric heart transplant patient. AB - Autoimmune-mediated bowel disease has been reported after pediatric heart transplantation. Recognition and treatment of these patients has been difficult. We describe a patient who responded to steroids and basiliximab therapy after an inflammatory process secondary to abnormal T-cell activation. Our patient is a 28 month-old female who received a heart transplant at five wk of age. At 24 months post-transplant, she developed fever and bloody stools. Initial investigations were significant for an elevated ESR (>120) and CRP (15.2). Symptoms persisted despite bowel rest and mycophenolate discontinuation. Endoscopic evaluation revealed discontinuous ulcerative disease involving esophagus, terminal ileum, right and left colon, necessitating extensive bowel resection. She had additional airway inflammation leading to a TEF at the site of esophageal ulceration, requiring tracheostomy. Immune evaluation revealed autoimmune dysregulation that responded to parenteral methylprednisolone. Chronic basiliximab therapy allowed for successful weaning of steroids with sustained remission. She has been transitioned to sirolimus and tacrolimus maintenance immunosuppression with plans to discontinue basiliximab once off steroids. In conclusion, bowel disease in the setting of pediatric heart transplantation can be severe and refractory to traditional treatment methods. Tailoring immune therapy to activated T cells can result in remission. Basiliximab therapy was used in our patient to maintain steroid-induced remission, but long-term complications of this disease process are unknown. PMID- 26374669 TI - Unusual reflectance confocal microscopy findings during the examination of a perianal nevus: pinworms. PMID- 26374668 TI - Short-term suppression of Aedes aegypti using genetic control does not facilitate Aedes albopictus. AB - BACKGROUND: Under permit from the National Biosafety Commission for the use of genetically modified organisms, releases of a genetically engineered self limiting strain of Aedes aegypti (OX513A) were used to suppress urban pest Ae. aegypti in West Panama. Experimental goals were to assess the effects on a coexisting population of Ae. albopictus and examine operational parameters with relevance to environmental impact. RESULTS: Ae. albopictus populations were shown to be increasing year upon year at each of three study sites, potentially reflecting a broader-scale incursion into the area. Ae. albopictus abundance was unaffected by a sustained reduction in Ae. aegypti by up to 93% through repeated releases of OX513A. Males accounted for 99.99% of released OX513A, resulting in a sustained mating fraction of 75%. Mean mating competitiveness of OX513A was 0.14. The proportion of OX513A in the local environment decreased by 95% within 25 days of the final release. CONCLUSIONS: There was no evidence for species replacement of Ae. aegypti by Ae. albopictus over the course of this study. No unintentional environmental impacts or elevated operational risks were observed. The potential for this emerging technology to mitigate against disease outbreaks before they become established is discussed. PMID- 26374670 TI - Hydrazine-mediated strongly coupled Re(CO)3 dimers. AB - Dimeric metal complexes can often exhibit coupling interactions via bridging ligands. In this report, we present two Re(CO)3 dimers, where the metals are linked via a bis(pyca) hydrazine (pyca = pyridine-2-carbaldehyde imine) Schiff base ligand. For the dimeric compounds 4 and 5, we observe strong coupling across the dimer as measured by cyclic voltammetry: ~480 mV separations between the first and the second reduction waves that correspond to comproportionation constants close to 1.5 * 10(8). Evidence for a mixed valence state upon one electron reduction was also observed by spectroelectrochemistry in which a clear inter-valence charge-transfer (IVCT) band was observed in [4]- and [5]-complexes. The electronic structures of all target compounds were probed by DFT and TDDFT computational methods. DFT calculations indicate that reduction takes place at the diimine units, and that the observed coupling is a ligand-based phenomenon, rather than one that involves metal-based orbitals. PMID- 26374671 TI - Epidemiological Study of Child Casualties of Landmines and Unexploded Ordnances: A National Study from Iran. AB - BACKGROUND: Despite landmine-risk education programs and extensive demining activities on the Western border of Iran, landmines and unexploded ordnance (UXOs) still cause civilian and child casualties three decades after the Iraq Iran war (1980-1988). The objective of this study was to understand the epidemiological patterns and risk factors of injury in child casualties of landmines and UXOs in Western and Southwestern Iran. METHODS: Children who were 18 years old or younger at the time of study and who sustained injuries from landmines and UXOs were identified through a search at the Iranian National Veterans Registry. These children participated in a 5-day gathering. The information on socioeconomic status, health-related issues, quality of life, health care utilization, and clinical profiles concerning the landmine and UXO injuries were collected. The method of data collection consisted of three component surveys: health interview, social survey, and medical examinations. Social surveys and health interviews were conducted in a face-to-face method by utilizing a questionnaire consisting of 39 questions addressing household and individual components, including information on time and type of injuries, physical activity, mental health, and quality of life. A comprehensive team of physicians in different subspecialties evaluated and examined children to assess the current medical and psychiatric conditions and physical activity, and recommended and arranged further medical, rehabilitation, or surgical planning. RESULTS: Seventy-eight child casualties were identified and participated in the study. The mean age of the participants at the time of study was 16.11 years old (SD=2 years). The mean age of victims at the time of injury was 8.2 years (SD=3.12 years; ranged from 2 to 15 years old). Sixty-seven (85.9%) of the children were male. Provinces of Kurdistan and Kermanshah had the highest number of casualties, with a total number of 54 children (68.3%). Eighty percent of the injuries were caused by landmines, and UXO explosions were reported in 20% of the cases. Overall, 24 children (30%) had received some landmine-risk education before or after the events. Sixty percent of the explosions had happened in the morning between 9:00 am and 12:00 pm. Playing and grazing livestock were the most prevalent activities/reasons at the time of injury, which were reported in 77% of the subjects. Sixty-three percent of incidents had multiple casualties and in only 13 explosions were the children the only victims of the explosion. The most prevalent injuries were amputations in 41 subjects (52.56%), followed by hearing loss in 23 subjects (29.5%). Amputations were more common in upper extremities (62%) than in lower extremities (38%). CONCLUSION: Landmines and UXOs comprise a significant safety hazard to the children living in the Western border of Iran decades after the Iraq-Iran War. The large number of injuries and lack of risk training among victims suggest that landmine cleanings and landmine-risk education should be age-specifically targeted and expanded substantially. PMID- 26374672 TI - Seven neurons memorizing sequences of alphabetical images via spike-timing dependent plasticity. AB - An artificial neural network, such as a Boltzmann machine, can be trained with the Hebb rule so that it stores static patterns and retrieves a particular pattern when an associated cue is presented to it. Such a network, however, cannot effectively deal with dynamic patterns in the manner of living creatures. Here, we design a dynamic Boltzmann machine (DyBM) and a learning rule that has some of the properties of spike-timing dependent plasticity (STDP), which has been postulated for biological neural networks. We train a DyBM consisting of only seven neurons in a way that it memorizes the sequence of the bitmap patterns in an alphabetical image "SCIENCE" and its reverse sequence and retrieves either sequence when a partial sequence is presented as a cue. The DyBM is to STDP as the Boltzmann machine is to the Hebb rule. PMID- 26374673 TI - Ultrabrief delirium assessments--are they ready for primetime? PMID- 26374674 TI - Relaxation-compensated CEST-MRI at 7 T for mapping of creatine content and pH- preliminary application in human muscle tissue in vivo. AB - The small biomolecule creatine is involved in energy metabolism. Mapping of the total creatine (mostly PCr and Cr) in vivo has been done with chemical shift imaging. Chemical exchange saturation transfer (CEST) allows an alternative detection of creatine via water MRI. Living tissue exhibits CEST effects from different small metabolites, including creatine, with four exchanging protons of its guanidinium group resonating about 2 ppm from the water peak and hence contributing to the amine proton CEST peak. The intermediate exchange rate (~ 1000 Hz) of the guanidinium protons requires high RF saturation amplitude B1. However, strong B1 fields also label semi-solid magnetization transfer (MT) effects originating from immobile protons with broad linewidths (~kHz) in the tissue. Recently, it was shown that endogenous CEST contrasts are strongly affected by the MT background as well as by T1 relaxation of the water protons. We show that this influence can be corrected in the acquired CEST data by an inverse metric that yields the apparent exchange-dependent relaxation (AREX). AREX has some useful linearity features that enable preparation of both concentration, and--by using the AREX-ratio of two RF irradiation amplitudes B1- purely exchange-rate-weighted CEST contrasts. These two methods could be verified in phantom experiments with different concentration and pH values, but also varying water relaxation properties. Finally, results from a preliminary application to in vivo CEST imaging data of the human calf muscle before and after exercise are presented. The creatine concentration increases during exercise as expected and as confirmed by (31)P NMR spectroscopic imaging. However, the estimated concentrations obtained by our method were higher than the literature values: cCr,rest=24.5+/-3.74mM to cCr,ex=38.32+/-13.05mM. The CEST based pH method shows a pH decrease during exercise, whereas a slight increase was observed by (31)P NMR spectroscopy. PMID- 26374675 TI - Structural models of intrinsically disordered and calcium-bound folded states of a protein adapted for secretion. AB - Many Gram-negative bacteria use Type I secretion systems, T1SS, to secrete virulence factors that contain calcium-binding Repeat-in-ToXin (RTX) motifs. Here, we present structural models of an RTX protein, RD, in both its intrinsically disordered calcium-free Apo-state and its folded calcium-bound Holo state. Apo-RD behaves as a disordered polymer chain comprising several statistical elements that exhibit local rigidity with residual secondary structure. Holo-RD is a folded multi-domain protein with an anisometric shape. RTX motifs thus appear remarkably adapted to the structural and mechanistic constraints of the secretion process. In the low calcium environment of the bacterial cytosol, Apo-RD is an elongated disordered coil appropriately sized for transport through the narrow secretion machinery. The progressive folding of Holo RD in the extracellular calcium-rich environment as it emerges form the T1SS may then favor its unidirectional export through the secretory channel. This process is relevant for hundreds of bacterial species producing virulent RTX proteins. PMID- 26374676 TI - Exploring the ethical and regulatory issues in pragmatic clinical trials. AB - The need for high-quality evidence to support decision making about health and health care by patients, physicians, care providers, and policy-makers is well documented. However, serious shortcomings in evidence persist. Pragmatic clinical trials that use novel techniques including emerging information and communication technologies to explore important research questions rapidly and at a fraction of the cost incurred by more "traditional" research methods promise to help close this gap. Nevertheless, while pragmatic clinical trials can bridge clinical practice and research, they may also raise difficult ethical and regulatory challenges. In this article, the authors briefly survey the current state of evidence that is available to inform clinical care and other health-related decisions and discuss the potential for pragmatic clinical trials to improve this state of affairs. They then propose a new working definition for pragmatic research that centers upon fitness for informing decisions about health and health care. Finally, they introduce a project, jointly undertaken by the National Institutes of Health Health Care Systems Research Collaboratory and the National Patient-Centered Clinical Research Network (PCORnet), which addresses 11 key aspects of current systems for regulatory and ethical oversight of clinical research that pose challenges to conducting pragmatic clinical trials. In the series of articles commissioned on this topic published in this issue of Clinical Trials, each of these aspects is addressed in a dedicated article, with a special focus on the interplay between ethical and regulatory considerations and pragmatic clinical research aimed at informing "real-world" choices about health and health care. PMID- 26374677 TI - Use of altered informed consent in pragmatic clinical research. AB - There are situations in which the requirement to obtain conventional written informed consent can impose significant or even insurmountable barriers to conducting pragmatic clinical research, including some comparative effectiveness studies and cluster-randomized trials. Although certain federal regulations governing research in the United States (45 CFR 46) define circumstances in which any of the required elements may be waived, the same standards apply regardless of whether any single element is to be waived or whether consent is to be waived in its entirety. Using the same threshold for a partial or complete waiver limits the options available to institutional review boards as they seek to optimize a consent process. In this article, we argue that new standards are necessary in order to enable important pragmatic clinical research while at the same time protecting patients' rights and interests. PMID- 26374678 TI - Harmonization and streamlining of research oversight for pragmatic clinical trials. AB - The oversight of research involving human participants is a complex process that requires institutional review board review as well as multiple non-institutional review board institutional reviews. This multifaceted process is particularly challenging for multisite research when each site independently completes all required local reviews. The lack of inter-institutional standardization can result in different review outcomes for the same protocol, which can delay study operations from start-up to study completion. Hence, there have been strong calls to harmonize and thus streamline the research oversight process. Although the institutional review board is only one of the required reviews, it is often identified as the target for harmonization and streamlining. Data regarding variability in decision-making and interpretation of the regulations across institutional review boards have led to a perception that variability among institutional review boards is a primary contributor to the problems with review of multisite research. In response, many researchers and policymakers have proposed the use of a single institutional review board of record, also called a central institutional review board, as an important remedy. While this proposal has merit, the use of a central institutional review board for multisite research does not address the larger problem of completing non-institutional review board institutional review in addition to institutional review board review-and coordinating the interdependence of these reviews. In this article, we describe the overall research oversight process, distinguish between institutional review board and institutional responsibilities, and identify challenges and opportunities for harmonization and streamlining. We focus on procedural and organizational issues and presume that the protection of human subjects remains the paramount concern. Suggested modifications of institutional review board processes that focus on time, efficiency, and consistency of review must also address what effect such changes have on the quality of review. We acknowledge that assessment of quality is difficult in that quality metrics for institutional review board review remain elusive. At best, we may be able to assess the time it takes to review protocols and the consistency across institutions. PMID- 26374679 TI - Data monitoring committees for pragmatic clinical trials. AB - In any clinical trial, it is essential to monitor the accumulating data to be sure that the trial continues to be safe for participants and that the trial is being conducted properly. Data monitoring committees, independent expert panels who undertake regular reviews of the data as the trial progresses, serve an important role in safeguarding the interests of research participants and ensuring trial integrity in many trials. Many pragmatic clinical trials, which aim to inform healthcare decisions by comparing alternate interventions in heterogeneous healthcare delivery settings, will warrant review by an independent data monitoring committee due to their potential impact on clinical practice. However, the very features that make a trial "pragmatic" may pose challenges in terms of which aspects of a trial to monitor and when it is appropriate for a data monitoring committee to intervene. Using the Pragmatic-Explanatory Continuum Indicator Summary tool that draws distinctions between pragmatic and explanatory clinical trials, we review characteristics of pragmatic clinical trials that may have implications for data monitoring committees and interim monitoring plans. These include broad eligibility criteria, a focus on subjective patient-centered outcomes, and in some cases a lack of standardized follow-up procedures across study sites. Additionally, protocol adherence is often purposefully not addressed in pragmatic trials in order to accurately represent the clinical practice setting and maintain practicability of implementation; there are differing viewpoints as to whether adherence should be assessed and acted upon by data monitoring committees in these trials. Some other issues not specifically related to the Pragmatic-Explanatory Continuum Indicator Summary criteria may also merit special consideration in pragmatic trials. Thresholds for early termination of a pragmatic clinical trial might be controversial. The distinguishing features of pragmatic clinical trials require careful consideration when developing interim data monitoring plans, and trial sponsors, investigators, and data monitoring committees should agree on a plan before trial inception. Finally, special expertise, such as an informatics, may be helpful on data monitoring committees for some pragmatic clinical trials. Patient representatives may provide particularly valuable insights in the monitoring process. PMID- 26374680 TI - Harms, benefits, and the nature of interventions in pragmatic clinical trials. AB - To produce evidence capable of informing healthcare decision making at all critical levels, pragmatic clinical trials are diverse both in terms of the type of intervention (medical, behavioral, and/or technological) and the target of intervention (patients, clinicians, and/or healthcare system processes). Patients and clinicians may be called on to participate as designers, investigators, intermediaries, or subjects of pragmatic clinical trials. Other members of the healthcare team, as well as the healthcare system itself, also may be affected directly or indirectly before, during, or after study implementation. This diversity in the types and targets of pragmatic clinical trial interventions has brought into focus the need to consider whether existing ethics and regulatory principles, policies, and procedures are appropriate for pragmatic clinical trials. Specifically, further examination is needed to identify how the types and targets of pragmatic clinical trial interventions may influence the assessment of net potential risk, understood as the balance of potential harms and benefits. In this article, we build on scholarship seeking to align ethics and regulatory requirements with potential research risks and propose an approach to the assessment of net risks that is sensitive to the diverse nature of pragmatic clinical trial interventions. We clarify the potential harms, burdens, benefits, and advantages of common types of pragmatic clinical trial interventions and discuss implications for patients, clinicians, and healthcare systems. PMID- 26374682 TI - Privacy and confidentiality in pragmatic clinical trials. AB - With pragmatic clinical trials, an opportunity exists to answer important questions about the relative risks, burdens, and benefits of therapeutic interventions. However, concerns about protecting the privacy of this information are significant and must be balanced with the imperative to learn from the data gathered in routine clinical practice. Traditional privacy protections for research uses of identifiable information rely disproportionately on informed consent or authorizations, based on a presumption that this is necessary to fulfill ethical principles of respect for persons. But frequently, the ideal of informed consent is not realized in its implementation. Moreover, the principle of respect for persons-which encompasses their interests in health information privacy-can be honored through other mechanisms. Data anonymization also plays a role in protecting privacy but is not suitable for all research, particularly pragmatic clinical trials. In this article, we explore both the ethical foundation and regulatory framework intended to protect privacy in pragmatic clinical trials. We then review examples of novel approaches to respecting persons in research that may have the added benefit of honoring patient privacy considerations. PMID- 26374681 TI - The ethics and regulatory landscape of including vulnerable populations in pragmatic clinical trials. AB - Policies have been developed to protect vulnerable populations in clinical research, including the US federal research regulations (45 Code of Federal Regulations 46 Subparts B, C, and D). These policies generally recognize vulnerable populations to include pregnant women, fetuses, neonates, children, prisoners, persons with physical handicaps or mental disabilities, and disadvantaged persons. The aim has been to protect these populations from harm, often by creating regulatory and ethical checks that may limit their participation in many clinical trials. The recent increase in pragmatic clinical trials raises at least two questions about this approach. First, is exclusion itself a harm to vulnerable populations, as these groups may be denied access to understanding how health interventions work for them in clinical settings? Second, are groups considered vulnerable in traditional clinical trials also vulnerable in pragmatic clinical trials? We argue first that excluding vulnerable subjects from participation in pragmatic clinical trials can be harmful by preventing acquisition of data to meaningfully inform clinical decision-making in the future. Second, we argue that protections for vulnerable subjects in traditional clinical trial settings may not be translatable, feasible, or even ethical to apply in pragmatic clinical trials. We conclude by offering specific recommendations for appropriately protecting vulnerable research subjects in pragmatic clinical trials, focusing on pregnant women, fetuses, neonates, children, prisoners, persons with physical handicaps or mental disabilities, and disadvantaged persons. PMID- 26374683 TI - Gatekeepers for pragmatic clinical trials. AB - To successfully implement a pragmatic clinical trial, investigators need access to numerous resources, including financial support, institutional infrastructure (e.g. clinics, facilities, staff), eligible patients, and patient data. Gatekeepers are people or entities who have the ability to allow or deny access to the resources required to support the conduct of clinical research. Based on this definition, gatekeepers relevant to the US clinical research enterprise include research sponsors, regulatory agencies, payers, health system and other organizational leadership, research team leadership, human research protections programs, advocacy and community groups, and clinicians. This article provides a framework to help guide gatekeepers' decision-making related to the use of resources for pragmatic clinical trials. Relevant ethical considerations for gatekeepers include (1) concern for the interests of individuals, groups, and communities affected by the gatekeepers' decisions, including protection from harm and maximization of benefits; (2) advancement of organizational mission and values; and (3) stewardship of financial, human, and other organizational resources. Separate from these ethical considerations, gatekeepers' actions will be guided by relevant federal, state, and local regulations. This framework also suggests that to further enhance the legitimacy of their decision-making, gatekeepers should adopt transparent processes that engage relevant stakeholders when feasible and appropriate. We apply this framework to the set of gatekeepers responsible for making decisions about resources necessary for pragmatic clinical trials in the United States, describing the relevance of the criteria in different situations and pointing out where conflicts among the criteria and relevant regulations may affect decision-making. Recognition of the complex set of considerations that should inform decision-making will guide gatekeepers in making justifiable choices regarding the use of limited and valuable resources. PMID- 26374684 TI - The Food and Drug Administration and pragmatic clinical trials of marketed medical products. AB - Pragmatic clinical trials can help answer questions of comparative effectiveness for interventions routinely used in medical practice. Pragmatic clinical trials may examine outcomes of one or more marketed medical products, and they are heterogeneous in design and risk. The Food and Drug Administration is charged with protecting the rights, safety, and welfare of individuals enrolled in clinical investigations, as well as assuring the integrity of the data upon which approval of medical products is made. The Food and Drug Administration has broad jurisdiction over drugs and medical devices (whether or not they are approved for marketing), and as such, clinical investigations of these products are subject to applicable Food and Drug Administration regulations. While many pragmatic clinical trials will meet the criteria for an exemption from the requirements for an investigational new drug application or investigational device exemption, in general, all clinical investigations of medical products that fall under Food and Drug Administration jurisdiction must adhere to regulations for informed consent and review by an institutional review board. We are concerned that current Food and Drug Administration requirements for obtaining individual informed consent may deter or delay the conduct of pragmatic clinical trials intended to develop reliable evidence of comparative safety and effectiveness of approved medical products that are regulated by the Food and Drug Administration. Under current regulations, there are no described mechanisms to alter or waive informed consent to make it less burdensome or more practicable for low-risk pragmatic clinical trials. We recommend that the Food and Drug Administration establish a risk-based approach to obtaining informed consent in pragmatic clinical trials that would facilitate the conduct of pragmatic clinical trials without compromising the protection of enrolled individuals or the integrity of the resulting data. PMID- 26374685 TI - Oversight on the borderline: Quality improvement and pragmatic research. AB - Pragmatic research that compares interventions to improve the organization and delivery of health care may overlap, in both goals and methods, with quality improvement activities. When activities have attributes of both research and quality improvement, confusion often arises about what ethical oversight is, or should be, required. For routine quality improvement, in which the delivery of health care is modified in minor ways that create only minimal risks, oversight by local clinical or administrative leaders utilizing institutional policies may be sufficient. However, additional consideration should be given to activities that go beyond routine, local quality improvement to first determine whether such non-routine activities constitute research or quality improvement and, in either case, to ensure that independent oversight will occur. This should promote rigor, transparency, and protection of patients' and clinicians' rights, well-being, and privacy in all such activities. Specifically, we recommend that (1) health care organizations should have systematic policies and processes for designating activities as routine quality improvement, non-routine quality improvement, or quality improvement research and determining what oversight each will receive. (2) Health care organizations should have formal and explicit oversight processes for non-routine quality improvement activities that may include input from institutional quality improvement experts, health services researchers, administrators, clinicians, patient representatives, and those experienced in the ethics review of health care activities. (3) Quality improvement research requires review by an institutional review board; for such review to be effective, institutional review boards should develop particular expertise in assessing quality improvement research. (4) Stakeholders should be included in the review of non-routine quality improvement and quality improvement-related research proposals. Only by doing so will we optimally leverage both pragmatic research on health care delivery and local implementation through quality improvement as complementary activities for improving health. PMID- 26374686 TI - Considerations in the evaluation and determination of minimal risk in pragmatic clinical trials. AB - Institutional review boards, which are charged with overseeing research, must classify the riskiness of proposed research according to a federal regulation known as the Common Rule (45 CFR 46, Subpart A) and by regulations governing the US Food and Drug Administration codified in 21 CFR 50. If an institutional review board determines that a clinical trial constitutes "minimal risk," there are important practical implications: the institutional review board may then allow a waiver or alteration of the informed consent process; the study may be carried out in certain vulnerable populations; or the study may be reviewed by institutional review boards using an expedited process. However, it is unclear how institutional review boards should assess the risk levels of pragmatic clinical trials. Such trials typically compare existing, widely used medical therapies or interventions in the setting of routine clinical practice. Some of the therapies may be considered risky of themselves but the study comparing them may or may not add to that pre-existing level of risk. In this article, we examine the common interpretations of research regulations regarding minimal-risk classifications and suggest that they are marked by a high degree of variability and confusion, which in turn may ultimately harm patients by delaying or hindering potentially beneficial research. We advocate for a clear differentiation between the risks associated with a given therapy and the incremental risk incurred during research evaluating those therapies as a basic principle for evaluating the risk of a pragmatic clinical trial. We then examine two pragmatic clinical trials and consider how various factors including clinical equipoise, practice variation, research methods such as cluster randomization, and patients' perspectives may contribute to current and evolving concepts of minimal-risk determinations, and how this understanding in turn affects the design and conduct of pragmatic clinical trials. PMID- 26374687 TI - Ethical responsibilities toward indirect and collateral participants in pragmatic clinical trials. AB - Pragmatic clinical trials are designed to inform decision makers about the benefits, burdens, and risks of health interventions in real-world settings. Pragmatic clinical trials often use for research purposes data collected in the course of clinical practice. The distinctive features of pragmatic clinical trials demand fresh thinking about what is required to act properly toward people affected by their conduct, in ways that go beyond ensuring the protection of rights and welfare for "human research subjects" under conventional research ethics regulations. To stimulate such work, we propose to distinguish among categories of research participants in pragmatic clinical trials as follows: Direct participants: (1) individuals being directly intervened upon and/or (2) individuals from whom personal identifiable data are being collected for the purposes of the pragmatic clinical trial. Indirect participants: individuals who are (1) not identified as direct participants and (2) whose rights and welfare may be affected by the intervention through their routine exposure to the environment in which the intervention is being deployed. Collateral participants: patient groups and other stakeholder communities who may be otherwise affected by the occurrence and findings of the pragmatic clinical trial. We illustrate these distinctions with case examples and discuss the distinctive responsibilities of researchers and pragmatic clinical trial leadership toward each type of participant. We suggest that pragmatic clinical trial investigators, institutional review boards, health systems leaders, and others engaged in the research enterprise work together to identify these participants. For indirect participants, risks and benefits to which they are exposed should be weighed to ensure that their rights and welfare are protected accordingly, and communication strategies should be considered to help them make well-informed decisions. Collateral participants could provide input on the design, planning, and conduct of a pragmatic clinical trial and offer insights regarding the best way to communicate the trial's results to their constituencies. PMID- 26374688 TI - AJP-Cell Theme: Cellular Responses to Hypoxia. PMID- 26374690 TI - Withholding temozolomide in glioblastoma patients with unmethylated MGMT promoter -still a dilemma? PMID- 26374692 TI - Making Sense of the Evidence: How to Read and Evaluate Research Publications. PMID- 26374693 TI - Three controversies over item disclosure in medical licensure examinations. AB - In response to views on public's right to know, there is growing attention to item disclosure - release of items, answer keys, and performance data to the public - in medical licensure examinations and their potential impact on the test's ability to measure competence and select qualified candidates. Recent debates on this issue have sparked legislative action internationally, including South Korea, with prior discussions among North American countries dating over three decades. The purpose of this study is to identify and analyze three issues associated with item disclosure in medical licensure examinations - 1) fairness and validity, 2) impact on passing levels, and 3) utility of item disclosure - by synthesizing existing literature in relation to standards in testing. Historically, the controversy over item disclosure has centered on fairness and validity. Proponents of item disclosure stress test takers' right to know, while opponents argue from a validity perspective. Item disclosure may bias item characteristics, such as difficulty and discrimination, and has consequences on setting passing levels. To date, there has been limited research on the utility of item disclosure for large scale testing. These issues requires ongoing and careful consideration. PMID- 26374689 TI - Coordination of self-renewal in glioblastoma by integration of adhesion and microRNA signaling. AB - BACKGROUND: Cancer stem cells (CSCs) provide an additional layer of complexity for tumor models and targets for therapeutic development. The balance between CSC self-renewal and differentiation is driven by niche components including adhesion, which is a hallmark of stemness. While studies have demonstrated that the reduction of adhesion molecules, such as integrins and junctional adhesion molecule-A (JAM-A), decreases CSC maintenance. The molecular circuitry underlying these interactions has yet to be resolved. METHODS: MicroRNA screening predicted that microRNA-145 (miR-145) would bind to JAM-A. JAM-A overexpression in CSCs was evaluated both in vitro (proliferation and self-renewal) and in vivo (intracranial tumor initiation). miR-145 introduction into CSCs was similarly assessed in vitro. Additionally, The Cancer Genome Atlas dataset was evaluated for expression levels of miR-145 and overall survival of the different molecular groups. RESULTS: Using patient-derived glioblastoma CSCs, we confirmed that JAM-A is suppressed by miR-145. CSCs expressed low levels of miR-145, and its introduction decreased self-renewal through reductions in AKT signaling and stem cell marker (SOX2, OCT4, and NANOG) expression; JAM-A overexpression rescued these effects. These findings were predictive of patient survival, with a JAM A/miR-145 signature robustly predicting poor patient prognosis. CONCLUSIONS: Our results link CSC-specific niche signaling to a microRNA regulatory network that is altered in glioblastoma and can be targeted to attenuate CSC self-renewal. PMID- 26374694 TI - Adjunctive Systemic Corticosteroids for Hospitalized Community-Acquired Pneumonia: Systematic Review and Meta-Analysis 2015 Update. AB - Previous randomized controlled trials (RCTs) and meta-analyses evaluated the efficacy and safety of adjunctive corticosteroids for community-acquired pneumonia (CAP). However, the results from them had large discrepancies. The eligibility criteria for the current meta-analysis were original RCTs written in English as a full article that evaluated adjunctive systemic corticosteroids adding on antibiotic therapy targeting typical and/or atypical pathogen for treating hospitalized human CAP cases. Four investigators independently searched for eligible articles through PubMed, Embase, and Cochrane databases. Random model was used. The heterogeneity among original studies and subgroups was evaluated with the I(2) statistics. Of 54 articles that met the preliminary criteria, we found 10 eligible RCTs comprising 1780 cases. Our analyses revealed following pooled values by corticosteroids. OR for all-cause death: 0.80 (95% confidence interval (95% CI) 0.53-1.21) from all studies; 0.41 (95% CI 0.19-0.90) from severe-case subgroup; 0.21 (95% CI 0.0-0.74) from intensive care unit (ICU) subgroup. Length of ICU stay: -1.30 days (95% CI (-3.04)-0.44). Length of hospital stay: -0.98 days (95% CI (-1.26)-(-0.71)). Length to clinical stability: -1.16 days (95% CI (-1.73)-(-0.58)). Serious complications do not seem to largely increase by steroids. In conclusion, adjunctive systemic corticosteroids for hospitalized patients with CAP seems preferred strategies. PMID- 26374695 TI - 'Laba' garlic processed by dense phase carbon dioxide: the relation between green colour generation and cellular structure, alliin consumption and alliinase activity. AB - BACKGROUND: 'Laba' garlic is usually processed by soaking garlic in vinegar for more than 1 week during winter. It is popular for its unique green colour and tasty flavour. Greening is desirable and required for this product as its characteristic. Dense phase carbon dioxide (DPCD) had a significant effect on the greening of intact garlic (Allium sativum L.) cloves. The relation between green colour generation and alliin consumption, alliinase activity and the cellular structure of garlic, respectively, were investigated in this work. The effects of treatment time, pressure and temperature of DPCD were also analysed and discussed. RESULTS: DPCD had a significant effect on the cellular structure of garlic cells. Garlic protoplast underwent greater morphological change after DPCD treatments at higher temperatures while the amount of precipitate increased with greater treatment time and temperature. Common trends on garlic greening and alliin consumption were observed except for DPCD treatment at 10 MPa and 65 degrees C. The alliinase activity decreased with increasing treatment time, pressure and temperature. It reached the lowest level at 13 MPa and 55 degrees C. CONCLUSION: The formation of the green colour was a comprehensive result of DPCD on changing cellular structure, alliin consumption and alliinase activity. DPCD treatment at 10 MPa and 55 degrees C was the optimum condition for the greening of 'Laba' garlic. This work further facilitated the application of DPCD in the industrial production of 'Laba' garlic. (c) 2015 Society of Chemical Industry. PMID- 26374697 TI - Ochratoxin A in liquorice products - a review. AB - Liquorice is a herbal medicine produced mainly in China and Iran. This plant is suspected to contain ochratoxin A (OTA), a secondary metabolite produced by fungi. Although liquorice is not included in the daily dietary of humans, the high levels of OTA reported in this product have concerned consumers. Registration of a standard method for measuring the amount of this mycotoxin in liquorice-derived products is an important challenge and requires the introduction of a reliable, simple, fast-performance and reproducible technique. This review examines studies carried out concerning the occurrence of OTA in liquorice products. Recent information regarding contaminated liquorice, the regulatory framework and methods to degrade OTA in liquorice are discussed. PMID- 26374696 TI - Breathing retraining for African-American adolescents with asthma: a pilot study of a school-based randomized controlled trial. AB - OBJECTIVE: Asthma affects approximately seven million children/adolescents in the USA, with African-American children disproportionately affected. Breathing retraining techniques have been shown to improve asthma outcomes in adults, though research in youth is limited. The purpose of this pilot study was to test the feasibility and preliminary efficacy of a school-based randomized controlled trial of breathing retraining for asthma outcomes and anxiety symptoms in a sample of urban, African-American adolescents. METHODS: Adolescents were randomized into either the intervention group (20-min breathing retraining plus education) or control group (20-min standard education). Participants completed two study visits, one month apart. Asthma control, asthma quality of life and lung functioning (FEV1 and peak flow) were the primary outcomes, and state anxiety (pre-post the intervention) and trait anxiety (over the one-month period) were the secondary outcomes. RESULTS: Thirty-three African-American adolescents participated in the study, with a 90% retention rate between visit 1 and visit 2. Asthma control and asthma quality of life, significantly improved over time (p <= 0.01) with no differences between intervention and control groups. State anxiety significantly decreased (p <= 0.01) immediately post intervention at both time points with no differences between groups. There were no significant differences found in lung functioning or trait anxiety over the one-month time period. CONCLUSIONS: These preliminary results suggest that breathing retraining is a feasible, acceptable and potentially efficacious intervention (although no significant differences between groups were found) for improving asthma symptoms in urban adolescents with asthma in a school-based setting. PMID- 26374698 TI - Family involvement for breast cancer decision making among Chinese-American women. AB - BACKGROUND: To describe family involvement in decision making for primary treatment in Chinese-American women with early-stage breast cancer. METHODS: Qualitative data were collected in 2003 from semi-structured questions in interviews with a sample of Chinese-American (ChA) women with breast cancer, who were recruited from the metropolitan New York area. Responses to the questions were written in Chinese immediately during the interview and read back to the subject for accuracy and validation. Content analysis was used to inductively code and analyze the data to generate themes. RESULTS: The participants consisted of 123 ChA women with early stage breast cancer with a mean age of 48.7 years (+/ 9.3) and who had lived in the United States a median of 13.6 years. Support and Caring was the major theme that described family involvement in the breast cancer decision-making process. Gathering Information, Being There, Navigating the Health Care System, Maintaining Family Life and Making the Decision described the aspects of family support in the process. The majority of women described the treatment decision making as a collaborative supportive process with the family, but limited English fluency, strong opinions, lack of a shared perspective, distant living proximity and competing work responsibilities of family members were stressful for the women and perceived as non-supportive. CONCLUSIONS: Family involvement in health care decision making is culturally embedded in Asian populations. Culturally sensitive patient and family consultation strategies are needed to assist informed treatment decision making in Chinese-American women diagnosed with breast cancer. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26374699 TI - Most ADHD diagnoses made in US children seem to follow guidelines. PMID- 26374700 TI - Long-standing insulinoma: two case reports and review of the literature. AB - BACKGROUND: Insulinomas are rare pancreatic endocrine tumors. Most are benign and solitary. However, the nonspecific symptoms and small size of these tumors led to difficulties of diagnosis and localization. CASE PRESENTATION: We present two Arab patients with pancreatic long-standing insulinoma. Both patients presented episodic hypoglycemic symptoms respectively during 10 and 2 years. Biochemical and morphological workup detected localized pancreatic insulinoma. Open procedure surgery was done for the two patients and insulinomas were successfully removed by enucleation. CONCLUSION: Insulinoma remains a diagnostic challenge to practitioners. Diagnosis of suspected cases is easily confirmed by standard endocrine tests, especially the supervised fasting test. Accurate preoperative localization is essential for more effective and safest surgery. PMID- 26374701 TI - Severe parkinsonism associated with anti-CRMP5 antibody-positive paraneoplastic neurological syndrome and abnormal signal intensity in the bilateral basal ganglia. PMID- 26374702 TI - Factors influencing long-term outcomes in relapsing-remitting multiple sclerosis: PRISMS-15. AB - AIM: An exploratory study of the relationship between cumulative exposure to subcutaneous (sc) interferon (IFN) beta-1a treatment and other possible prognostic factors with long-term clinical outcomes in relapsing-remitting multiple sclerosis (RRMS). METHODS: Patients in the original PRISMS study were invited to a single follow-up visit 15 years after initial randomisation (PRISMS 15). Outcomes over 15 years were compared in the lowest and highest quartile of the cumulative sc IFN beta-1a dose groups, and according to total time receiving sc IFN beta-1a as a continuous variable per 5 years of treatment. Potential prognostic factors for outcomes were analysed. RESULTS: Of 560 patients randomised in PRISMS, 291 returned for PRISMS-15 and 290 (51.8%) were analysed. Higher cumulative dose exposure and longer treatment time appeared to be associated with better outcomes on: annualised relapse rate, number of relapses, time to Expanded Disability Status Scale (EDSS) progression, change in EDSS, proportions of patients with EDSS >= 4 or >= 6, <= 5 relapses and EDSS <4 or <6, and time to conversion to secondary-progressive MS (SPMS). Higher dose exposure was associated with lower proportions of patients with EDSS progression and conversion to SPMS, and longer time on treatment with lower risk of first relapse. Change in EDSS from baseline to 24 months was a strong predictor of evaluated clinical outcomes over 15 years. CONCLUSIONS: These findings suggest that higher cumulative exposure to sc IFN beta-1a may be associated with better clinical outcomes, and early change in EDSS score may have prognostic value, over many years, in RRMS. PMID- 26374703 TI - Minocycline as an adjunct for treatment-resistant depressive symptoms: study protocol for a pilot randomised controlled trial. AB - BACKGROUND: Depression is one of the leading causes of disability worldwide. A high proportion of patients do not respond to standard drug treatments. Recent evidence has suggested that anti-inflammatory treatment may have beneficial effects in major depression. Minocycline is a tetracycline antibiotic with good CNS penetration that exerts effects on multiple interacting symptoms implicated in the pathophysiology of mood disorders. Open-label studies have suggested that minocycline is effective as an adjunct drug in improving depressive symptoms. METHODS/DESIGN: This is a multi-centre, 3-month, double-blind, placebo controlled, pilot trial of minocycline added to treatment as usual for patients suffering from DSM-IV major depressive disorder. This will be a double-blind, randomised, controlled, two parallel-arm study with 20 participants in each arm, giving a total of 40 participants. There will be a screening visit, a randomization visit and four follow-up visits. Clinical assessments using the Hamilton Depression Rating Scale (HAM-D), Clinical Global Impression scale (CGI), Patient Health Questionnaire-9 (PHQ -9) and the Generalised Anxiety Disorder scale (GAD-7) will be carried out at every visit. Side effects checklists will also be undertaken at each visit. Biomarkers (inflammatory cytokines and CRP) will be measured at baseline and at the end of the treatment phase. Minocycline will be started at 100 mg once daily (OD) and will be increased to 200 mg at two weeks. DISCUSSION: Anti-inflammatory treatments have been shown to have some beneficial effects in the treatment of major depressive disorder. The aim of this pilot randomised controlled trial is to establish the degree of improvement in depressive symptoms with the addition of minocycline to treatment as usual. TRIAL REGISTRATION: ClinicalTrials.gov NCT02263872 registered 10 October 2014. PMID- 26374704 TI - Real-time prediction of mortality, readmission, and length of stay using electronic health record data. AB - OBJECTIVE: To develop a predictive model for real-time predictions of length of stay, mortality, and readmission for hospitalized patients using electronic health records (EHRs). MATERIALS AND METHODS: A Bayesian Network model was built to estimate the probability of a hospitalized patient being "at home," in the hospital, or dead for each of the next 7 days. The network utilizes patient specific administrative and laboratory data and is updated each time a new pathology test result becomes available. Electronic health records from 32 634 patients admitted to a Sydney metropolitan hospital via the emergency department from July 2008 through December 2011 were used. The model was tested on 2011 data and trained on the data of earlier years. RESULTS: The model achieved an average daily accuracy of 80% and area under the receiving operating characteristic curve (AUROC) of 0.82. The model's predictive ability was highest within 24 hours from prediction (AUROC = 0.83) and decreased slightly with time. Death was the most predictable outcome with a daily average accuracy of 93% and AUROC of 0.84. DISCUSSION: We developed the first non-disease-specific model that simultaneously predicts remaining days of hospitalization, death, and readmission as part of the same outcome. By providing a future daily probability for each outcome class, we enable the visualization of future patient trajectories. Among these, it is possible to identify trajectories indicating expected discharge, expected continuing hospitalization, expected death, and possible readmission. CONCLUSIONS: Bayesian Networks can model EHRs to provide real-time forecasts for patient outcomes, which provide richer information than traditional independent point predictions of length of stay, death, or readmission, and can thus better support decision making. PMID- 26374705 TI - A design of experiments approach to validation sampling for logistic regression modeling with error-prone medical records. AB - BACKGROUND AND OBJECTIVE: Electronic medical record (EMR) databases offer significant potential for developing clinical hypotheses and identifying disease risk associations by fitting statistical models that capture the relationship between a binary response variable and a set of predictor variables that represent clinical, phenotypical, and demographic data for the patient. However, EMR response data may be error prone for a variety of reasons. Performing a manual chart review to validate data accuracy is time consuming, which limits the number of chart reviews in a large database. The authors' objective is to develop a new design-of-experiments-based systematic chart validation and review (DSCVR) approach that is more powerful than the random validation sampling used in existing approaches. METHODS: The DSCVR approach judiciously and efficiently selects the cases to validate (i.e., validate whether the response values are correct for those cases) for maximum information content, based only on their predictor variable values. The final predictive model will be fit using only the validation sample, ignoring the remainder of the unvalidated and unreliable error prone data. A Fisher information based D-optimality criterion is used, and an algorithm for optimizing it is developed. RESULTS: The authors' method is tested in a simulation comparison that is based on a sudden cardiac arrest case study with 23 041 patients' records. This DSCVR approach, using the Fisher information based D-optimality criterion, results in a fitted model with much better predictive performance, as measured by the receiver operating characteristic curve and the accuracy in predicting whether a patient will experience the event, than a model fitted using a random validation sample. CONCLUSIONS: The simulation comparisons demonstrate that this DSCVR approach can produce predictive models that are significantly better than those produced from random validation sampling, especially when the event rate is low. PMID- 26374706 TI - Pack hunting by minute soil testate amoebae: nematode hell is a naturalist's paradise. PMID- 26374707 TI - Alleles versus mutations: Understanding the evolution of genetic architecture requires a molecular perspective on allelic origins. AB - Perspectives on the role of large-effect quantitative trait loci (QTL) in the evolution of complex traits have shifted back and forth over the past few decades. Different sets of studies have produced contradictory insights on the evolution of genetic architecture. I argue that much of the confusion results from a failure to distinguish mutational and allelic effects, a limitation of using the Fisherian model of adaptive evolution as the lens through which the evolution of adaptive variation is examined. A molecular-based perspective reveals that allelic differences can involve the cumulative effects of many mutations plus intragenic recombination, a model that is supported by extensive empirical evidence. I discuss how different selection regimes could produce very different architectures of allelic effects under a molecular-based model, which may explain conflicting insights on genetic architecture from studies of variation within populations versus between divergently selected populations. I address shortcomings of genome-wide association study (GWAS) practices in light of more suitable models of allelic evolution, and suggest alternate GWAS strategies to generate more valid inferences about genetic architecture. Finally, I discuss how adopting more suitable models of allelic evolution could help redirect research on complex trait evolution toward addressing more meaningful questions in evolutionary biology. PMID- 26374708 TI - Rats quit nicotine for a sweet reward following an extensive history of nicotine use. AB - Drug use may be exacerbated in environments which lack alternative means of engaging in rewarding behaviour. When alternative rewards are available, drug use may decrease-an effect that can be harnessed for therapeutic benefit. This idea is particularly well-supported by recent preclinical evidence demonstrating that a majority of rats will readily choose a potent non-drug reward over cocaine or heroin. Here we examine whether the same holds true for nicotine, a drug considered to have one of the highest addiction liabilities amongst drugs of abuse. Rats were trained to nose-poke separately for saccharin or nicotine on alternate days. Using a discrete-trial, forced-choice procedure, rats were then allowed to choose between nicotine and saccharin. This was followed by choice testing after a decrease in saccharin concentration (0.2-0%), omission of the fluid reward, an increase in nicotine concentration and following an extended nicotine self-administration history. All rats demonstrated a clear and immediate preference for saccharin at all times. This was despite variations in reward concentrations, or after an extensive nicotine history. Notably, rats preferred to nose-poke for water over nicotine and would omit responses when no fluid was delivered, rather than resume responding for nicotine. Overall, this study confirms and extends to nicotine previous research on other drugs of abuse, including cocaine and heroin. The ease with which rats quit nicotine in the present study contrasts with the well-known difficulty of humans to quit tobacco smoking. Possible factors that could explain this apparent discrepancy are discussed. PMID- 26374709 TI - Does the choice of EQ-5D tariff matter? A comparison of the Swedish EQ-5D-3L index score with UK, US, Germany and Denmark among type 2 diabetes patients. AB - OBJECTIVE: To compare the performance of the recently developed Swedish experience-based time trade-off (TTO) valuation of the EuroQol-5D-3L (EQ-5D-3L) against the hypothetical-based TTO valuations from UK, US, Germany and Denmark. METHODS: Type 2 diabetes patients from the Swedish National Diabetes Register (N = 1,757) responded to EQ-5D-3L questionnaire in 2008. Health utilities were compared using a range of parametric and nonparametric tests. Absolute agreement and consistency were investigated using intra-class correlations coefficients (ICCs) and Bland-Altman plots. Differences in health utilities between known groups were evaluated. Transition scores for pairs of observed EQ-5D-3L health states were calculated and compared. RESULTS: The Swedish tariff (SWT) resulted in substantially higher health utilities and differences were more profound for more severe health problems. ICC ranged 0.6 to 0.8 and Bland-Altman plots showed wide limits of agreement. While all tariffs discriminate between known-groups, the effect sizes were generally small. The SWT had higher (lower) known-group validity for macrovascular (microvascular) complications. The SWT and UK tariff were associated with the lowest and the highest mean absolute transition scores, respectively, for 2775 observed pairs of the EQ-5D-3L health states. CONCLUSION: There were systematic differences between the SWT and tariffs from other countries meaning that the choice of tariff might have substantial impact on funding decisions. The Swedish experienced-based TTO valuation will give higher priority to life-extending interventions than those which improve quality of life. We suggest that economic evaluations in Sweden include both Swedish experience-based and non-Swedish hypothetical-based valuations through a sensitivity analysis. PMID- 26374711 TI - Abstracts for the British Association of Dermatologists 95th Annual Meeting Manchester, U.K. 7-9 July 2015. PMID- 26374710 TI - Halorubrum yunnanense sp. nov., isolated from a subterranean salt mine. AB - Two halophilic archaeal strains, Q85(T) and Q86, were isolated from a subterranean salt mine in Yunnan, China. Cells were rod-shaped, Gram-stain negative and motile. Colonies were red, smooth, convex and round (1.0-2.0 mm in diameter). The orthologous 16S rRNA and rpoB9 gene sequences of these two strains were almost identical (99.5 and 99.7 % similarities). Their closest relatives were Halorubrum kocurii BG-1(T) (98.0-98.1 % 16S rRNA gene sequence similarity), Halorubrum aidingense 31-hong(T) (97.6-97.7 %) and Halorubrum lipolyticum 9-3T (97.5-97.6 %). The level of DNA-DNA relatedness between strains Q85(T) and Q86 was 90 %, while that between Q85(T) and other related Halorubrum strains was less than 30 % (29 % for H. kocurii BG-1(T), 25 % for H. aidingense 31-hong(T) and 22 % for H. lipolyticum 9-3(T)). Optimal growth of the two novel strains was observed with 20 % (w/v) NaCl and at 42-45 8C under aerobic conditions, with a slight difference in optimum Mg2+ concentration (0.7 M for Q85(T),0.5 M for Q86) and a notable difference in optimum pH (pH 7.5 for Q85(T), pH 6.6 for Q86). Anaerobic growth occurred with nitrate, but not with L-arginine or DMSO. The major polar lipids of the two strains were identical, including phosphatidylglycerol, phosphatidylglycerol phosphate methyl ester, phosphatidylglycerol sulfate and sulfated diglycosyl diether, which are the major lipids of the genus Halorubrum. The G+C contents of strains Q85(T) and Q86 were 66.3 and 66.8 %, respectively. Based on the phenotypic, chemotaxonomic and phylogenetic properties of strains Q85(T) and Q86, a novel species, Halorubrum yunnanense sp. nov., is proposed. The type strain is Q85(T) (=5CGMCC 1.15057(T)=JCM 30665(T)). PMID- 26374713 TI - British Association of Dermatologists: Officers and Committee 2014-2015. PMID- 26374712 TI - Foreword. PMID- 26374714 TI - Disclaimer. PMID- 26374715 TI - Vice President's Page. PMID- 26374716 TI - Gold-Catalyzed Intramolecular Tandem Cyclization of Indole-Ynamides: Diastereoselective Synthesis of Spirocyclic Pyrrolidinoindolines. AB - A gold-catalyzed intramolecular tandem cyclization of indole-ynamide affords tetracyclic spirocyclic pyrrolidinoindoline bearing an all-carbon quaternary stereocentre in a single step; however, when the reaction was carried out in the presence of BF3 ?Et2 O, the corresponding tricyclic spirocyclic pyrrolidinoindoline-based enones are produced through a key 1,5-hydride shift. The developed chemistry provides a diastereoselective and straightforward entry to structurally diverse polycylic pyrrolidinoindolines from indole-ynamides in one-pot reactions under mild conditions. PMID- 26374717 TI - [The relevance of a decline in renal function for risk of renal failure, cardiovascular events and all-cause mortality]. AB - It is well established that the presence of impaired renal function is associated with an increased risk of end-stage renal disease, cardiovascular events and all cause mortality. Irrespective of the starting level of renal function, a decline in renal function over two years is a relevant and strong risk factor for end stage renal disease, cardiovascular death and all-cause mortality. Even a decline of 20 to 30 per cent is associated with to a considerable increased risk and requires further attention. PMID- 26374718 TI - [Lifestyle and psychosocial health in Dutch adolescents: an additional point of contact in Dutch Preventive Child Healthcare]. AB - OBJECTIVE: This study aims to give an overview of the type, prevalence and accumulation of risk behaviours and psychosocial health problems in Dutch adolescents, and of potential interventions directed at dealing with them. DESIGN: Cross-sectional analyses of data from a cohort study, and literature review. METHOD: We used data from the prospective TRacking Adolescents' Individual Lives Survey (TRAILS) study (n=2230) and computed prevalences of risk behaviours and psychosocial health problems at the ages of 13 and 16 years. We assessed the evidence for effectiveness of preventive interventions in systematic reviews. RESULTS: Risk behaviours like insufficient consumption of fruit and vegetables and skipping breakfast were common among adolescents. Between 13 to 16 years the prevalence of overweight increased from 11.0% to 15.0%. The lifetime prevalence of smoking among the young people increased from 36.3% to 55.7% and of use of alcohol from 74.0% to 92.3%. Most risk behaviour prevalences were higher among adolescents with a lower educational level and those with two low-educated parents. These adolescents more commonly also had > 5 risk behaviours or psychosocial problems. The prevalence of depressive symptoms increased from 5.5% in 13-year-olds to 8.4% in 16-year-olds. The literature review showed that collective interventions, whether multifaceted or otherwise, may be particularly effective in the prevention of a high-risk lifestyle and overweight. Both indicated and collective prevention were effective for dealing with psychosocial problems. CONCLUSION: Both prevalence and accumulation of risk behaviours and psychosocial health problems increase during adolescence. The risks of these are higher in young people with lower levels of education. Appropriate monitoring is particularly important in this group. PMID- 26374719 TI - [Parenteral iron therapy in chronic kidney disease or chronic heart failure]. AB - Iron deficiency and anaemia occur frequently in patients with chronic kidney disease (CKD) or chronic heart failure (CHF) and are associated with lower quality of life and higher mortality. Treating anaemia with erythropoietic growth factors produces no improvement. In recent years, the focus has therefore shifted to correction of iron deficiency. Chronic inflammation in CKD increases the production of hepcidin, which blocks iron absorption from the intestine and leads to less efficient re-use of iron from the macrophages. In absolute iron deficiency the body's iron stores are depleted, whereas in functional iron deficiency the supply of iron is not sufficient to meet demand from the bone marrow. Normal or high ferritin levels do not exclude iron deficiency at tissue level. The iron saturation fraction is a more useful indicator. Parenteral iron therapy ameliorates in CHF the symptoms of iron deficiency, irrespective of the effect on haemoglobin levels. The long-term effects of intravenous iron on mortality and morbidity are still unknown. PMID- 26374720 TI - [Partial lipodystrophy: a spot diagnosis]. AB - BACKGROUND: Partial lipodystrophy is a rare acquired disorder characterised by gradual loss of subcutaneous adipose tissue in the upper half of the body. CASE DESCRIPTION: We saw a 9-year-old girl who had been referred on account of recurrent urinary tract infections. On physical examination, she was noticed to be very thin in the face. Her upper extremities were also skinny. Strikingly, the lower half of her body was normally proportioned, which immediately suggested a diagnosis of partial lipodystrophy. Additional examinations showed a low level of complement factor C3 and the presence of C3 nephritic factor. CONCLUSION: Partial lipodystrophy is rare but it is important to include it in the differential diagnosis of unwanted disproportional subcutaneous fat loss because of the somatic and psychological consequences. PMID- 26374721 TI - [A patient with vision problems: first manifestation of a neurodegenerative condition]. AB - BACKGROUND: Vision problems are common and the causes are diverse. This case illustrates the fact that vision problems may also be the first manifestation of a neurodegenerative disorder. CASE DESCRIPTION: A 46-year-old male developed progressive, incapacitating vision problems. Multiple pairs of glasses with lenses of different strengths did not improve symptoms. No ophthalmological explanation of the problems could be found. Oculomotor apraxia and visual extinction were seen on neurological examination. Visuoperceptual impairment was the main finding on neuropsychological examination. Impairment was also identified in visuoconstruction, memory and praxis. CONCLUSION: Cognitive problems in several areas, interference with activities of daily living, and young age of onset complete the clinical picture of presenile dementia. Posterior cortical atrophy is a spectrum of neurodegenerative disorders, characterized by progressive, incapacitating visuospatial and visuoperceptual impairment. The most prevalent underlying pathology is Alzheimer's disease. At present there is no curative therapy for posterior cortical atrophy. PMID- 26374722 TI - [Capnothorax following a diagnostic laparoscopy]. AB - An 84-year-old woman underwent a diagnostic laparoscopy preceding a planned total gastrectomy. A bilateral pneumothorax was diagnosed postoperatively, following an uneventful procedure. The patient's clinical parameters led to the diagnosis of capnothorax, a rare complication of laparoscopic surgery. It is important to be able to differentiate between a capnothorax and a pneumothorax because the treatment is different: a capnothorax can generally be treated conservatively. The perioperative signs and symptoms, physiology and treatment of a capnothorax are discussed in this article. PMID- 26374723 TI - [Many possible causes of variant angina]. AB - BACKGROUND: Variant angina, or vasospastic angina, is a form of angina caused by vasospasm of the coronary arteries, probably caused by endothelial dysfunction. This form of angina is provoked by non-classical risk factors such as stress, alcohol use, use of sympathomimetics and low environmental temperatures, but also by smoking. Treatment is based on elimination of risk factors and vasodilator therapy with nitrates and long-acting calcium antagonists. CASE DESCRIPTION: We present a 68-year-old woman with recurring thoracalgia at rest and during exercise, suggestive of severe variant angina in more than one coronary artery. Despite elimination of risk factors and administration of vasodilatory therapy the treatment was initially insufficient. It eventually emerged that the probable cause was frequent use of a vasoconstrictive nasal spray, although this was not described in literature, and not originally mentioned by the patient. CONCLUSION: A thorough case history is of vital importance in a patient presenting with a history suggestive of variant angina. Even undescribed and apparently less important risk factors can be responsible for persistence of symptoms, and can lead to an applied treatment not producing the desired result. PMID- 26374724 TI - [A man with a painful sternum]. AB - We present a case of a 81-year-old man with blunt chest trauma after a car accident. Trauma screening at the emergency department showed multiple rib fractures and a fractured sternum. We made the diagnosis floating sternum. Cardiac contusion may occur after chest-wall trauma, but was not present in this case. PMID- 26374725 TI - [Disclosing medical errors: the current situation]. AB - Recent broadly-supported guidelines stipulate that physicians and other care providers should be open and honest about incidents, i.e. medical errors. This standard has been reinforced by recent statements from the medical disciplinary board and is shortly expected to be incorporated into Dutch law. In daily practice many personal and institutional barriers hinder communication concerning medical errors. The implementation of an open disclosure policy, developed elsewhere, may assist in overcoming these barriers in the Netherlands. PMID- 26374726 TI - [Ambulant compression therapy for crural ulcers; an effective treatment when applied skilfully]. AB - The incidence of crural ulcers is high. They reduce quality of life considerably and create a burden on the healthcare budget. The key treatment is ambulant compression therapy (ACT). We describe two patients with crural ulcers whose ambulant compression treatment was suboptimal and did not result in healing. When the bandages were applied correctly healing was achieved. If correctly applied ACT should provide sufficient pressure to eliminate oedema, whilst taking local circumstances such as bony structures and arterial qualities into consideration. To provide pressure-to-measure regular practical training, skills and regular quality checks are needed. Knowledge of the properties of bandages and the proper use of materials for padding under the bandage enables good personalised ACT. In trained hands adequate compression and making use of simple bandages and dressings provides good care for patients suffering from crural ulcers in contrast to inadequate ACT using the same materials. PMID- 26374727 TI - [Risk factors for adverse effects of drugs: more research is necessary]. AB - When drugs are registered, relatively little is known about their adverse effects as clinical trials generally include only small numbers of patients and are of limited duration. New European legislation and the monitoring of adverse events are intended to enable the timely recognition of adverse effects of newly registered drugs. However, many adverse effects of commonly-used older drugs are already well-known. Therefore, in order to improve the quality of health care, research should also be focused on the risk factors associated with developing such adverse effects. PMID- 26374728 TI - [Maturity-onset diabetes of the young]. AB - Maturity-onset diabetes of the young (MODY) is the most common type of monogenic diabetes mellitus, estimated to account for approximately 1-4% of patients with diabetes. The predicted prevalence is, therefore, 20,000 patients in The Netherlands. Unfortunately less than 5% of these patients are confirmed by molecular genetic analysis. MODY is a clinically heterogeneous group of disorders caused by beta-cell dysfunction, which is caused by mutations in multiple genes. MODY is characterized by an early onset of diabetes (often before the age of 30 years) and autosomal dominant inheritance. Patients do not usually require insulin at diagnosis. To emphasize the importance of genetic analysis we describe a 7-year-old boy and his siblings with MODY type 2. Molecular genetic testing is essential for individual patient care, as treatment options differ between the various forms of MODY; it also provides an opportunity to screen relatives. PMID- 26374730 TI - Erratum to: Constructing a validity argument for the Objective Structured Assessment of Technical Skills (OSATS): a systematic review of validity evidence. PMID- 26374729 TI - The self-efficacy in patient-centeredness questionnaire - a new measure of medical student and physician confidence in exhibiting patient-centered behaviors. AB - BACKGROUND: Patient-centered communication is a core competency in modern health care and associated with higher levels of patient satisfaction, improved patient health outcomes, and lower levels of burnout among physicians. The objective of the present study was to develop a questionnaire assessing medical student and physician self-efficacy in patient-centeredness (SEPCQ) and explore its psychometric properties. METHODS: A preliminary 88-item questionnaire (SEPCQ-88) was developed based on a review of the literature and medical student portfolios and completed by 448 medical students from Aarhus University. Exploratory Principal Component analysis resulted in a 27-item version (SEPCQ-27) with three underlying self-efficacy factors: 1) Exploring the patient perspective, 2) Sharing information and power, and 3) Dealing with communicative challenges. The SEPCQ-27 was completed by an independent sample of 291 medical students from 2 medical schools and 101 hospital physicians. RESULTS: Internal consistencies of total and subscales were acceptable for both students and physicians (Cronbach's alpha (range): 0.74-0.95). There were no overall indications of gender-related differential item function (DIF), and a Confirmatory Factor Analysis (CFA) indicated good fit (CFI = 0.98; NNFI = 0.98; RMSEA = 0.05; SRMR = 0.07). Responsiveness was indicated by increases in SEPCQ scores after a course in communication and peer-supervision (Cohen's d (range): 0.21 to 0.73; p: 0.053 to 0.001). Furthermore, positive associations were found between increases in SEPCQ scores and course-related motivation to learn (medical students) and between SEPCQ scores and years of clinical experience (physicians). CONCLUSIONS: The final SEPCQ-27 showed satisfactory psychometric properties, and preliminary support was found for its construct validity, indicating that the SEPCQ-27 may be a valuable measure in future patient centered communication training and research. PMID- 26374731 TI - Hemodialysis for lithium poisoning. AB - BACKGROUND: Lithium salts, particularly lithium carbonate, are frequently used to treat bipolar disorder and mania. Lithium poisoning, which can occur as a result of reduced renal elimination, prescribing error, drug-drug interactions, or deliberate overdosage, produces neurologic injury that can be permanent. Hemodialysis is often recommended to treat lithium poisoning. Although hemodialysis clearly enhances the elimination of lithium, it is unclear whether this translates into improved patient outcomes. Evidence from observational studies, generally of low methodological quality, shows similar outcomes in patients managed with or without the use of hemodialysis. OBJECTIVES: To determine whether hemodialysis, applied in addition to standard therapy, reduces the likelihood, severity, or duration of neurological sequelae following lithium poisoning. SEARCH METHODS: We ran the search on 15 May 2015. We searched the Cochrane Injuries Group's Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE (OvidSP), Embase Classic+Embase (OvidSP), CINAHL Plus, clinical trials registers and four other databases. We screened the reference lists of relevant studies, textbook chapters, and review articles, and performed a Google search to identify grey literature. SELECTION CRITERIA: In the context of this review, hemodialysis was defined as any extracorporeal technique to filter and extract toxicants from the serum, including all forms of hemodialysis, hemofiltration, and continuous renal replacement techniques, but not peritoneal dialysis. We included any clinical trials in which patients were randomly allocated to receive, or not receive, hemodialysis in addition to standard care for lithium poisoning. DATA COLLECTION AND ANALYSIS: Two authors reviewed the abstracts of all identified articles. If either author identified an article as potentially meeting the inclusion criteria, both authors reviewed the full text of the article. MAIN RESULTS: No randomized controlled trials of hemodialysis therapy for lithium poisoning were identified. AUTHORS' CONCLUSIONS: Although the use of hemodialysis to enhance the elimination of lithium in patients with lithium poisoning appears logical, there is no evidence from randomized controlled trials to support nor refute the use of hemodialysis in the management of patients with lithium poisoning. PMID- 26374732 TI - Use of thiazolidinediones and the risk of elective hip or knee replacement: a population based case-control study. AB - AIMS: Osteoarthritis (OA) is the most common musculoskeletal condition in the elderly population. However, no disease modifying drug exists for this disease. In vivo animal studies have suggested that thiazolidinediones (TZD) may be used as disease modifying osteoarthritis drugs (DMOADs). To our knowledge, this has not yet been examined in humans before. The aim was to determine the risk of total joint replacement (TJR) in patients using TZDs compared with diabetic patients using other antidiabetic drugs. METHODS: A population based case-control study was performed using the Clinical Practice Research Datalink (CPRD). Cases (n = 94 609) were defined as patients >18 years of age who had undergone total knee (TKR) or hip replacement (THR) between 2000 and 2012. Controls were matched by age, gender and practice/surgery. Conditional logistic regression analyses were used to estimate the risk of TKR and THR with the use of TZDs in patients currently using one or more antidiabetic drugs. In order to determine effect with prolonged use, we also stratified TZD users by total number of prescriptions prior to surgery. We statistically adjusted our analyses for lifestyle factory, comorbidities and concomitant drug use. RESULTS: There was no difference in risk of TKR (OR 1.09, 95% CI 0.93, 1.27) and THR (OR 0.92, 95% CI 0.76, 1.10) when TZD users were compared with other AD users. Furthermore, we did not find an association with prolonged use of TZDs and TJR. CONCLUSION: Despite promising results from animal in vivo studies, this study did not find any evidence for a disease modifying osteoarthritic effect of TZDs. PMID- 26374733 TI - Regulation of germ cell function by SUMOylation. AB - Oogenesis and spermatogenesis are tightly regulated complex processes that are critical for fertility. Germ cells undergo meiosis to generate haploid cells necessary for reproduction. Errors in meiosis, including the generation of chromosomal abnormalities, can result in reproductive defects and infertility. Meiotic proteins are regulated by post-translational modifications including SUMOylation, the covalent attachment of small ubiquitin-like modifier (SUMO) proteins. Here, we review the role of SUMO proteins in controlling germ cell development and maturation based on recent findings from mouse models. Several studies have characterized the localization of SUMO proteins in male and female germ cells. However, a deeper understanding of how SUMOylation regulates proteins with essential roles in oogenesis and spermatogenesis will provide useful insight into the underlying mechanisms of germ cell development and fertility. PMID- 26374735 TI - Rubinstein Taybi Syndrome in an Indian Child due to EP300 Gene Mutation. PMID- 26374734 TI - Analysis of SCA8, SCA10, SCA12, SCA17 and SCA19 in patients with unknown spinocerebellar ataxia: a Thai multicentre study. AB - BACKGROUND: About 50 % of Thai patients with adult-onset spinocerebellar ataxia (SCA) was Machado-Joseph disease (MJD), SCA1, SCA2 and SCA6. The author investigated further on less common SCAs in the patients without any known mutations. METHODS: DNA samples of 82 index patients who were genetically excluded MJD, SCA1, SCA2, SCA6, SCA7 and dentatorubro-pallidoluysian atrophy (DRPLA) were examined. Analysis of SCA8, SCA10, SCA12, SCA17 and SCA19 genes were comprehensively performed. Normal range of trinucleotide repeat expansion sizes of TATA-box-binding protein gene (TBP) were also determined in 374 control subjects. RESULTS: Eight patients carried >=42 CAG/CAA repeat allele in the TBP consistent with SCA17. The pathological repeat alleles ranged from 42 to 57 repeats. All patients had significant degree of cognitive dysfunction. Other non ataxic phenotypes comprised of parkinsonism, chorea, dystonia and myoclonus. A sporadic patient carried a heterozygous 41-repeat allele developed chronic progressive cerebellar degeneration commenced at the age of 28 years. Whilst, 2 % of the control subjects (8/374) carried the 41-repeat allele. Five of the carriers were re-examined, and revealed that four of them had parkinsonism and/or cognitive impairment without cerebellar signs. Analysis of other types of SCAs was all negative. CONCLUSIONS: This is the first study of SCA8, SCA10, SCA12, SCA17 and SCA19 in Thais. SCA17 appears to be an important cause of ataxia in Thailand. Although, the pathological cut-off point of the TBP repeat allele remains unclear, the finding suggests that the 41-repeat may be a pathological allele resulting late-onset or mild phenotype. Apart from ataxia, cognitive impairment and parkinsonism may be clinical presentations in these carriers. PMID- 26374736 TI - Can Re-training in Baby Friendly Hospital Initiative (BFHI) Improve Breast Feeding Indicators? PMID- 26374737 TI - Is it Possible to Predict Mortality in Preterm Neonates, Based on a Single Troponin I Value at 24 h? PMID- 26374738 TI - Implications of Vitamin D Deficiency in Critically Ill Children. PMID- 26374739 TI - Obesity and Pulmonary Function Tests. PMID- 26374741 TI - Body mass index, abdominal fatness and the risk of gallbladder disease. AB - Epidemiological studies have indicated a positive association between adiposity and gallbladder disease risk, however, the shape of the dose-response relationship and differences between overall and abdominal adiposity remains to be clarified. We conducted a systematic review and dose-response meta-analysis of cohort studies of body mass index (BMI), waist circumference and waist-to-hip ratio and risk of gallbladder disease. PubMed and Embase databases were searched up to January 9th 2015. Summary relative risks were calculated using a random effects model. Seventeen prospective studies of BMI and gallbladder disease risk with 55,670 cases among 1,921,103 participants were included. The summary relative risk (RR) for a 5 unit increment in BMI was 1.63 (95 % CI 1.49-1.78, I(2) = 98 %). There was evidence of a nonlinear association overall and among women, p(nonlinearity) < 0.0001, but not among men, p(nonlinearity) = 0.99, with a slight flattening of the curve at very high BMI levels (BMI 40-45), however, the risk of gallbladder disease increased almost twofold even within the "normal" BMI range. The summary RR for a 10 cm increase in waist circumference was 1.46 (95 % CI 1.24-1.72, I(2) = 98 %, n = 5) and for a 0.1 unit increment in waist-to hip ratio was 1.44 (95 % CI 1.26-1.64, I(2) = 92 %, n = 4). Associations were attenuated, but still significant, when BMI and abdominal adiposity measures were mutually adjusted. Our results confirm a positive association between both general and abdominal fatness and the risk of gallbladder disease. There is an almost twofold increase in the risk even within the "normal" BMI range, suggesting that even moderate increases in BMI may increase risk. PMID- 26374742 TI - A conceptual disease model for adult Pompe disease. AB - BACKGROUND: Studies in orphan diseases are, by nature, confronted with small patient populations, meaning that randomized controlled trials will have limited statistical power. In order to estimate the effectiveness of treatments in orphan diseases and extrapolate effects into the future, alternative models might be needed. The purpose of this study is to develop a conceptual disease model for Pompe disease in adults (an orphan disease). This conceptual model describes the associations between the most important levels of health concepts for Pompe disease in adults, from biological parameters via physiological parameters, symptoms and functional indicators to health perceptions and final health outcomes as measured in terms of health-related quality of life. METHODS: The structure of the Wilson-Cleary health outcomes model was used as a blueprint, and filled with clinically relevant aspects for Pompe disease based on literature and expert opinion. Multiple observations per patient from a Dutch cohort study in untreated patients were used to quantify the relationships between the different levels of health concepts in the model by means of regression analyses. RESULTS: Enzyme activity, muscle strength, respiratory function, fatigue, level of handicap, general health perceptions, mental and physical component scales and utility described the different levels of health concepts in the Wilson-Cleary model for Pompe disease. Regression analyses showed that functional status was affected by fatigue, muscle strength and respiratory function. Health perceptions were affected by handicap. In turn, self-reported quality of life was affected by health perceptions. CONCLUSIONS: We conceptualized a disease model that incorporated the mechanisms believed to be responsible for impaired quality of life in Pompe disease. The model provides a comprehensive overview of various aspects of Pompe disease in adults, which can be useful for both clinicians and policymakers to support their multi-faceted decision making. PMID- 26374740 TI - TRPs and pain. AB - Nociception is the process of transmission of painful signals by nociceptors in the primary afferent nerve fibers, which specifically respond to noxious stimuli. These noxious stimuli are detected by nociceptors and converted into electrical signals, which are then transmitted to the spinal cord, thalamus, and the cerebral cortex, where pain is finally sensed. Transient receptor potential (TRP) ion channels have emerged as a family of evolutionarily conserved ligand-gated ion channels that function as molecular detectors of physical stimuli. Several member of this family, at least six channels from three TRP family subtypes (TRPV1-4, TRPM8, and TRPA1), are expressed in nociceptors, where they act as transducers for signals from thermal, chemical, and mechanical stimuli and play crucial roles in the generation and development of pathological pain perception. This review focuses on the increasing evidence of TRP channel involvement and contribution in nociceptive pain and the pain hypersensitivity associated with peripheral inflammation or neuropathy, and on the renewed interest in targeting TRP channels for pain relief. PMID- 26374743 TI - N-Acetyl Cysteine (NAC) in the Treatment of Obsessive-Compulsive Disorder: A 16 Week, Double-Blind, Randomised, Placebo-Controlled Study. AB - BACKGROUND: Obsessive-compulsive disorder (OCD) is a disabling mental illness for which pharmacological and psychosocial interventions are all too often inadequate. Recent preclinical and clinical studies have implicated dysfunction of glutamatergic neurotransmission in the pathophysiology of OCD. The amino acid based nutraceutical N-acetyl cysteine (NAC) is a safe and readily available agent that has been found to modify the synaptic release of glutamate in subcortical brain regions via modulation of the cysteine-glutamate antiporter. OBJECTIVE: The aim of this study was to assess the efficacy and safety of NAC in treating OCD. METHODS: A 16-week, double-blind, placebo-controlled, randomised trial using 3 g/day of NAC (1.5 g twice daily) in 44 participants (aged 18-70 years) with Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) diagnosed OCD, during 2013-2015. The primary outcome measure was the Yale-Brown Obsessive Compulsive Scale (YBOCS), conducted every 4 weeks. RESULTS: Analysis of the full sample (intention-to-treat) with repeated measures mixed linear modelling revealed a nonsignificant time * treatment interaction for the YBOCS scale total score (p = 0.39). A per-protocol analysis removing protocol violators also failed to show a significant time * treatment interaction for YBOCS total score (p = 0.15). However, a significant time * treatment interaction was observed for the YBOCS 'Compulsions' subscale in favour of NAC (p = 0.013), with a significant reduction observed at week 12 (dissipating at week 16). At 16 weeks, only four (20%) participants were considered 'responders' (YBOCS >=35% reduction at endpoint) versus four (27%) in the placebo group. The NAC was well tolerated, aside from more cases of heartburn occurring compared with placebo (p = 0.045). CONCLUSION: Further research involving NAC for OCD may require larger samples to detect moderate or small effect sizes, involve dosage or formulation differences, use in concert with exposure therapy, or an additional post-study observational period to mitigate study withdrawal. TRIAL REGISTRATION: ACTRN12613000310763. PMID- 26374744 TI - mAPKL: R/ Bioconductor package for detecting gene exemplars and revealing their characteristics. AB - BACKGROUND: So far many algorithms have been proposed towards the detection of significant genes in microarray analysis problems. Several of those approaches are freely available as R-packages though their engagement in gene expression analysis by non-bioinformaticians is usually a frustrating task. Besides, only some of those packages offer a complete suite of tools starting from initial data import and ending to analysis report. Here we present an R/Bioconductor package that implements a hybrid gene selection method along with a bunch of functions to facilitate a thorough and convenient gene expression profiling analysis. RESULTS: mAPKL is an open-source R/Bioconductor package that implements the mAP-KL hybrid gene selection method. The advantage of this method is that selects a small number of gene exemplars while achieving comparable classification results to other well established algorithms on a variety of datasets and dataset sizes. The mAPKL package is accompanied with extra functionalities including (i) solid data import; (ii) data sampling following a user-defined proportion; (iii) preprocessing through several normalization and transformation alternatives; (iv) classification with the aid of SVM and performance evaluation; (v) network analysis of the significant genes (exemplars), including degree of centrality, closeness, betweeness, clustering coefficient as well as the construction of an edge list table; (vi) gene annotation analysis, (vii) pathway analysis and (viii) auto-generated analysis reporting. CONCLUSIONS: Users are able to run a thorough gene expression analysis in a timely manner starting from raw data and concluding to network characteristics of the selected gene exemplars. Detailed instructions and example data are provided in the R package, which is freely available at Bioconductor under the GPL-2 or later license http://www.bioconductor.org/packages/3.1/bioc/html/mAPKL.html. PMID- 26374745 TI - TETIS study: evaluation of new topical hemostatic agent TT-173 in tooth extraction. AB - OBJECTIVES: TT-173 is a new hemostatic agent consisting of yeast-derived microvesicles containing a modified version of recombinant human tissue factor. In the present work, the procoagulant activity of TT-173 has been evaluated for the first time in humans. METHODS: This is a phase I, randomized, placebo controlled study to evaluate the efficacy, safety, systemic absorption, and immunogenicity of TT-173 in healthy volunteers undergoing tooth extraction. Subjects received TT-173 or placebo into the alveolar cavity, just after tooth extraction. Time to clot formation, bleeding time, and adverse events were recorded. RESULTS: Treatment with TT-173 reduced the bleeding time and the time to clot formation. No adverse events related with product administration were reported. In the same way, neither systemic absorption nor immunogenic reaction against the product was detected. Our findings pave the way to evaluate the usefulness of this new topical hemostatic agent in more complex oral surgeries and in those patients affected with coagulation disorders that may compromise the realization of dental procedures. CONCLUSION: The new hemostatic agent TT-173 has proven efficacious and safe in healthy subjects undergoing tooth extraction supporting its further evaluation in more complex surgeries. CLINICAL RELEVANCE: The development of this new topical hemostatic agent could contribute to bleeding control in oral and maxillofacial surgery. PMID- 26374746 TI - In vivo validation of near-infrared light transillumination for interproximal dentin caries detection. AB - OBJECTIVES: The aims of this clinical study were to investigate the diagnostic accuracy of near-infrared light transillumination (NILT) as a novel X-ray-free method for proximal dentin caries detection and to compare this method to established diagnostic methods. MATERIALS AND METHODS: A total of 127 interproximal dentin caries lesions without any cavity within visible dentin in posterior teeth from 85 consecutively selected patients were included. Visual and radiographic diagnoses and laser fluorescence measurements were available. NILT images were obtained, and a dentin lesion was predicted if a demineralisation involved the enamel-dentin junction (NILT-EDJ) or a shadow in dentin was detectable (NILT-dentin). Included lesions were opened and validated (reference standard). The statistical analyses included descriptive analyses and calculations of sensitivity, specificity and Az values. RESULTS: The diagnostic accuracy with respect to the reference standard was 1.6% for visual inspection, 66.7% for laser fluorescence, 96.1% for digital radiography, 29.1% for NILT dentin and 99.2% for NILT-EDJ. Bitewings (Az 0.984) and NILT-EDJ (Az 0.992) performed equally. CONCLUSION: Given the lack of true negatives in the study, the diagnostic accuracy of NILT achieved the same level as bitewings for the detection of proximal dentin caries. CLINICAL RELEVANCE: This study might indicate that NILT could reduce the usage of bitewings. PMID- 26374747 TI - Management of the premaxilla in the treatment of bilateral cleft of lip and palate: what can the literature tell us? AB - OBJECTIVE: In the treatment of bilateral cleft lip and palate (BCLP) patients, there is discussion about the management of the position of the premaxilla. This literature analysis summarises the literature on managing this condition. MATERIALS AND METHODS: A PubMed, Embase and Cochrane Library search was conducted resulting in 4465 articles which were screened on title and abstract. RESULTS: Seventy-one articles were available in full text, 16 of which were included in this literature analysis. We searched on keywords timing and technique, complications, growth of the maxilla and results after bone grafting the alveolar process. This literature analysis has shown that there are various ways to correct the position of the premaxilla. These can be divided into primary, early, late secondary and tertiary intervention before the age of 8 years, between the ages of 8 and 12 years and older than 12 years. Correction is done with surgery, orthodontics or a combination, with or without bone grafting. CONCLUSIONS: An osteotomy of the premaxilla in combination with secondary alveolar bone grafting appears to be the most successful technique. Combining early secondary alveolar bone grafting with osteotomy creates more room to ensure a watertight closure of the nasal mucosa resulting in fewer postoperative complications. Before surgery, the orthodontist should try to optimise the position of the premaxilla for its surgical correction prior to bone grafting. CLINICAL RELEVANCE: The treatment of BCLP patients is still based on experience and expert opinions. This literature analysis tries to give a summery on how to handle the protruded and displaced premaxilla. PMID- 26374749 TI - A Doctor's Testimony: Medical Neutrality and the Visibility of Palestinian Grievances in Jewish-Israeli Publics. AB - This paper follows the testimony of Izzeldin Abuelaish, a Palestinian physician who bears witness to his experiences working, living, and suffering under Israeli rule. He presents his story as a doctor's story, drawing on his identity as a medical professional to gain credibility and visibility and to challenge the limited legitimacy of Palestinian grievances. In this paper, I explore his testimony as a medical voice that at once recounts the suffering and loss endured by the Palestinian people and also struggles to negotiate the values associated with being a "reliable" witness. Consequently, I ethnographically examine the social life and reception of his story in Jewish-Israeli publics. In comparison with most Palestinian narratives, Abuelaish's testimony achieved an extremely rare degree of visibility and sympathy, a phenomenon that calls out for analysis. I identify the boundaries that typically render Palestinian grievances invisible to Israeli publics and suggest how medicine's self-proclaimed ethos of neutrality served as a channel for crossing them. Finally, I reflect on the political possibilities and limitations of medical witnessing to render suffering visible and arouse compassion toward those construed as a dangerous/enemy Other. PMID- 26374748 TI - Short fibre-reinforced composite for extensive direct restorations: a laboratory and computational assessment. AB - OBJECTIVES: The objective of the study was to evaluate the effectiveness of a short fibre-reinforced composite (FRC) applied in combination with a conventional filler composite (CFC) on the fatigue resistance, fracture strength, failure mode and stress distribution, for restorations of premolars under two loading angles. MATERIAL AND METHODS: Thirty-two inferior premolars received extensive cavities with removal of the lingual cusp. Teeth were restored directly using 'FRC (EverX Posterior, GC) + CFC (G-aenial, GC)' or 'CFC only' and received two fatigue/fracture loadings at two different angles (0 degrees /45 degrees ) (n = 8). Data were submitted to two-way ANOVA (alpha = 5 %) and Tukey test. Failure mode was analysed using SEM. Four 3D finite element (FE) models were constructed and static, linear and elastic analyses were performed. Maximum principal and von Mises stresses were evaluated. RESULTS: All specimens survived the mechanical fatigue simulation. No statistical difference in fracture resistance was recorded between FRC + CFC and CFC only, considering both loading angles (p = 0.115). However, the 0 degrees loading showed a statistical significant higher strength than the 45 degrees loading (p = 0.000). Failure mode analysis revealed more repairable fractures upon 0 degrees loading, versus more root fractures (unrepairable) upon 45 degrees loading. FE revealed a higher amount of stress upon 45 degrees loading, with tensile stress being imposed to the lingual cervical area. CONCLUSION: The fracture strength was not increased using the FRC. Loading at a 45 degrees decreased significantly the fracture resistance. CLINICAL RELEVANCE: The restoration of extensive cavities in posterior tooth is a challenge for the clinicians and the choice of the material that increases the fracture strength of tooth-restoration complex is required. PMID- 26374750 TI - The Biopsychosocial Model: "Reports of My Death Have Been Greatly Exaggerated". PMID- 26374751 TI - Clinical significance of psychiatric comorbidity in children and adolescents with obsessive-compulsive disorder: subtyping a complex disorder. AB - A promising approach in relation to reducing phenotypic heterogeneity involves the identification of homogeneous subtypes of OCD based on age of onset, gender, clinical course and comorbidity. This study aims to assess the sociodemographic characteristics and clinical features of OCD patients in relation to gender and the presence or absence of another comorbid disorder. The sample comprised 112 children and adolescents of both sexes and aged 8-18 years, all of whom had a diagnosis of OCD. Overall, 67 % of OCD patients had one comorbid diagnosis, 20.5 % had two such diagnoses and 2.6 % had three comorbid diagnoses. The group of OCD patients with a comorbid neurodevelopmental disorder had significantly more family history of OCD in parents (p = .049), as compared with the no comorbidity group and the group with a comorbid internalizing disorder, and they also showed a greater predominance of males (p = .013) than did the group with a comorbid internalizing disorder. The group of OCD patients with internalizing comorbidity had a later age of onset of OCD (p = .001) compared with both the other groups. Although the initial severity was similar in all three groups, the need for pharmacological treatment and for hospitalization due to OCD symptomatology was greater in the groups with a comorbid neurodevelopmental disorder (p = .038 and p = .009, respectively) and a comorbid internalizing disorder (p = .008 and p = .004, respectively) than in the group without comorbidity. Our findings suggest that two subtypes of OCD can be defined on the basis of the comorbid pathology presented. The identification of different subtypes according to comorbidity is potentially useful in terms of understanding clinical variations, as well as in relation to treatment management and the use of therapeutic resources. PMID- 26374752 TI - Routine endoscopic ultrasound in moderate and indeterminate risk patients of suspected choledocholithiasis to avoid unwarranted ERCP: A prospective randomized blinded study. AB - BACKGROUND: Endoscopic ultrasound (EUS) is the most sensitive test for diagnosis of common bile duct stones and it may avoid unnecessary endoscopic retrograde cholangiopancreatography (ERCP). AIM: The purpose of this study was to evaluate whether EUS done initially would avoid unnecessary ERCP in patients with moderate or indeterminate risk for occurrence of choledocholithiasis. METHODS: Patients with biliary colic or acute biliary pancreatitis, who were referred for suspected choledocholithiasis on the basis of alterations in liver function tests were prospectively included over 12 months period in blinded randomized fashion. Endoscopic ultrasonography was performed for all patients. Patients were randomized to two groups. ERCP was done in all patients in group A irrespective of the EUS findings, while in the group B, ERCP was done only in those patients in whom EUS was suggested the presence of common bile duct stone or sludge. RESULTS: A total of 50 patients were randomized into each group. EUS diagnosed common bile duct stones in 24 out of 50 patients (48 %) in group A, and ERCP identified common bile duct stones in 23 of those 24 patients. Twenty-eight out of 50 patients had common bile duct stones/sludge in group B, which were removed by subsequent ERCP. However, ERCP could be avoided in 22 cases (44 %) of group B and none of these patients had biliary symptoms up to 6 months of follow up. CONCLUSION: In patients with moderate or indeterminate risk for choledocholithiasis, prior EUS done for confirmation of choledocholithiasis avoids unnecessary ERCP in almost half of the cases. PMID- 26374753 TI - Prevalence of celiac disease in adult patients with iron-deficiency anemia of obscure origin in Kashmir (India). AB - OBJECTIVES: The purpose of this study was to evaluate the prevalence of celiac disease in adult patients with iron-deficiency anemia of obscure origin. METHODS: One hundred and sixty-one consecutive patients with iron-deficiency anemia of obscure origin were evaluated. Tissue transglutaminase antibodies levels were done and duodenal biopsies were scored according to Marsh classification. Diagnosis was based on positive IgA anti-tissue transglutaminase antibodies and abnormal histopathology. Gluten-free diet (GFD) was adviced for celiac disease patients. One hundred and sixty healthy blood donors were tested for IgA anti tissue transglutaminase antibodies, and positive controls were subjected to endoscopic duodenal biopsy. RESULTS: Tissue transglutaminase antibodies were positive in 13 (8 %) patients with iron-deficiency anemia of obscure origin and 4 (2.5 %) in control group (p = 0.026) (odds ratio 3.42; 95 % confidence interval [CI]: 1.092-10.743). All 13 patients (8 %) and 2 out of 4 positive controls (1.25 %) had histopathology findings of celiac disease (p = 0.004). Duodenal biopsy showed Marsh grade 1 in 4, grade 2 in 4 (30.77 %), 3a in 1 (7.70 %), 3b in 2 (15.38 %), and 3c in 2 (15.38 %) patients. A statistically significant correlation was found between lower hemoglobin concentration and higher Marsh grading (Spearman's rho = -0.946, p = 0.001). Celiac disease patients adhered to GFD and after 6 months mean (SD) hemoglobin levels increased from 7.42 +/- 0.96 to 10.47 +/- 0.80 g/dL (p- < 0.001). CONCLUSION: Patients with iron-deficiency anemia of obscure origin had increased prevalence of celiac disease. Gluten-free diet improved anemia in celiac disease patients irrespective of grade of duodenal involvement. PMID- 26374755 TI - Idiopathic congenital atrophoderma of Pasini and Pierini. PMID- 26374754 TI - Exploring the Ancestral Mechanisms of Regulation of Horizontally Acquired Nitrogenases. AB - The vast majority of Pseudomonas species are unable to fix atmospheric nitrogen. Although several studies have demonstrated that some strains belonging to the genus Pseudomonas sensu stricto do have the ability to fix nitrogen by the expression of horizontally acquired nitrogenase, little is known about the mechanisms of nitrogenase adaptation to the new bacterial host. Recently, we transferred the nitrogen fixation island from Pseudomonas stutzeri A1501 to the non-nitrogen-fixing bacterium Pseudomonas protegens Pf-5, and interestingly, the resulting recombinant strain Pf-5 X940 showed an uncommon phenotype of constitutive nitrogenase activity. Here, we integrated evolutionary and functional approaches to elucidate this unusual phenotype. Phylogenetic analysis showed that polyhydroxybutyrate (PHB) biosynthesis genes from natural nitrogen fixing Pseudomonas strains have been acquired by horizontal transfer. Contrary to Pf-5 X940, its derived PHB-producing strain Pf-5 X940-PHB exhibited the inhibition of nitrogenase activity under nitrogen-excess conditions, and displayed the typical switch-on phenotype observed in natural nitrogen-fixing strains after nitrogen deficiency. This indicates a competition between PHB production and nitrogen fixation. Therefore, we propose that horizontal transfer of PHB biosynthesis genes could be an ancestral mechanism of regulation of horizontally acquired nitrogenases in the genus Pseudomonas. PMID- 26374756 TI - Sydenham's chorea: not gone but perhaps forgotten. AB - Sydenham's chorea (SC) is characterised by chorea, emotional lability and hypotonia. In this study, we investigated the incidence and clinical presentation of childhood SC in Ireland (years 2006-2014). Nineteen cases were diagnosed. Five patients had rheumatic fever. An increasing trend with an incidence of 0.23/100 000 is reported. As most referral diagnoses included psychogenic illness, head injury and stroke, modern physicians may not be aware of this age old illness. A review of the manifestations and diagnosis of SC is presented. PMID- 26374757 TI - Turnover of Species and Guilds in Shrub Spider Communities in a 100-Year Postlogging Forest Chronosequence. AB - Disturbance of forests by logging and subsequent forest succession causes marked changes in arthropod communities. Although vegetation cover provides important habitat for arthropods, studies of the changes in their community structure associated with forest succession have been conducted mostly at ground level. To evaluate how forests of different ages contribute to arthropod biodiversity in shrub habitat, spiders were collected from shrubs in 12 forests ranging in age from 1 to 107 yr after logging. We found marked changes in spider community structure about 10 yr after logging: the number of species and individuals declined rapidly after this time. These changes were likely caused by a decrease in shrub cover in association with forest succession. Changes in spider species composition associated with stand age were small in forests at least 11 yr old and were not clustered by forest age. After the exclusion of species of which we sampled only one or two individuals incidentally, just 0.9 +/- 0.5 (mean +/- SD) species were unique to these older forests. The other 41.2 +/- 4.3 species found in these forests were common to both older and young forests, although some of these species in common were found mainly in forests at least 11 yr old. These results suggest that preservation of old-growth forests contributes to the abundance of these common species, although old-growth forests contribute little to species diversity. PMID- 26374758 TI - Avanex Unique Endophyte Technology: Reduced Insect Food Source at Airports. AB - Birds and other forms of wildlife are a major issue for airport authorities worldwide, as they can create hazards to operating aircraft. Wildlife "strikes," the majority caused by birds, can cause damage to operating aircraft and in severe cases lead to a loss of human life. Many airfields contain large areas of ground cover herbage alongside their runways that consist of mixtures of grasses, legumes, and weeds that can harbor many invertebrates. Many airfields use insecticides to control insect populations; however, mounting pressure from regional councils and water boards aim to reduce this practice due to ground water runoff and contamination concerns. Avanex Unique Endophyte Technology, a product specifically developed to reduce the attractiveness of airports and surrounding areas to birds, is based on a novel association between a selected strain of Epichloe endophyte and a turf-type tall fescue cultivar. This grass endophyte association acts through a direct mechanism whereby a negative response in birds is created through taste aversion and postingestion feedback as well as an indirect mechanism by deterring many invertebrates, a food source of many bird species. PMID- 26374759 TI - Response letter: "ATF3: A promoter or inhibitor of cardiac maladaptive remodeling". PMID- 26374760 TI - Evolving Genital Structures: A Deep Look at Network Co-option. AB - Novel body structures are often generated by the redeployment of ancestral components of the genome. In this issue of Developmental Cell, Glassford et al. (2015) present a thorough analysis of the co-option of a gene regulatory network in the origin of an evolutionary novelty. PMID- 26374761 TI - The Immunology of Breast Development. AB - The immune system is not normally viewed as a regulator of breast development. However, in this issue of Developmental Cell, Plaks et al. (2015) reveal that antigen-presenting cells and T cells have a key role in controlling the development of the mammary gland's epithelial ductal network. PMID- 26374762 TI - Secrets of the Hair Follicle: Now on Your iPhone. AB - Skin development requires communication between epithelial and mesenchymal cells, melanocytes, and neurons. In this issue of Developmental Cell, Sennett et al. (2015) shed new light on these mechanisms by simultaneously profiling multiple different cell types in embryonic mouse skin at the onset of hair follicle formation. PMID- 26374763 TI - Adhesive Enrichment and Membrane Turnover at the Heart of Cardiopharyngeal Induction. AB - Differential inductive signaling during asymmetric division of progenitor cells specifies the heart lineage in Ciona intestinalis. In this issue of Developmental Cell, Cota and Davidson (2015) show that differential induction is mediated by FGF receptor regionalization, resulting from asymmetric cell-matrix adhesion and reduced mitotic turnover of polarized Caveolin-rich membrane domains. PMID- 26374764 TI - Effects of intermittent fasting on body composition and clinical health markers in humans. AB - Intermittent fasting is a broad term that encompasses a variety of programs that manipulate the timing of eating occasions by utilizing short-term fasts in order to improve body composition and overall health. This review examines studies conducted on intermittent fasting programs to determine if they are effective at improving body composition and clinical health markers associated with disease. Intermittent fasting protocols can be grouped into alternate-day fasting, whole day fasting, and time-restricted feeding. Alternate-day fasting trials of 3 to 12 weeks in duration appear to be effective at reducing body weight (~3%-7%), body fat (~3-5.5 kg), total cholesterol (~10%-21%), and triglycerides (~14%-42%) in normal-weight, overweight, and obese humans. Whole-day fasting trials lasting 12 to 24 weeks also reduce body weight (~3%-9%) and body fat, and favorably improve blood lipids (~5%-20% reduction in total cholesterol and ~17%-50% reduction in triglycerides). Research on time-restricted feeding is limited, and clear conclusions cannot be made at present. Future studies should examine long-term effects of intermittent fasting and the potential synergistic effects of combining intermittent fasting with exercise. PMID- 26374765 TI - High-fat diet amplifies renal renin angiotensin system expression, blood pressure elevation, and renal dysfunction caused by Ceacam1 null deletion. AB - Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAMl), a substrate of the insulin receptor tyrosine kinase, regulates insulin action by promoting insulin clearance. Global null mutation of Ceacam1 gene (Cc1(-/-)) results in features of the metabolic syndrome, including insulin resistance, hyperinsulinemia, visceral adiposity, elevated blood pressure, and albuminuria. It also causes activation of the renal renin-angiotensin system (RAS). In the current study, we tested the hypothesis that high-fat diet enhances the expression of RAS components. Three-month-old wild-type (Cc1(+/+)) and Cc1(-/-) mice were fed either a regular or a high-fat diet for 8 wk. At baseline under regular feeding conditions, Cc1(-/-) mice exhibited higher blood pressure, urine albumin-to-creatinine ratio (UACR), and renal expression of angiotensinogen, renin/prorenin, angiotensin-converting enzyme, (pro)renin receptor, angiotensin subtype AT1 receptor, angiotensin II, and elevated PI3K phosphorylation, as detected by p85alpha (Tyr(508)) immunostaining, inflammatory response, and the expression of collagen I and collagen III. In Cc1(+/+) mice, high-fat diet increased blood pressure, UACR, the expression of angiotensin-converting enzyme and angiotensin II, PI3K phosphorylation, inflammatory response, and the expression of collagen I and collagen III. In Cc1(-/-) mice, high-fat intake further amplified these parameters. Immunohistochemical staining showed increased p-PI3K p85alpha (Tyr(508)) expression in renal glomeruli, proximal, distal, and collecting tubules of Cc1(-/-) mice fed a high-fat diet. Together, this demonstrates that high-fat diet amplifies the permissive effect of Ceacam1 deletion on renal expression of all RAS components, PI3K phosphorylation, inflammation, and fibrosis. PMID- 26374769 TI - NHS needs emergency injection of L1bn, says King's Fund. PMID- 26374766 TI - Vasodilator responses and endothelin-dependent vasoconstriction in metabolically healthy obesity and the metabolic syndrome. AB - Patients with metabolically healthy obesity (MHO) do not present the cluster of metabolic abnormalities that define the metabolic syndrome (MetS). Whether MHO is associated with lower impairment of vasoreactivity than the MetS is unknown. For this purpose, forearm blood flow (FBF) responses were measured by strain-gauge plethysmography during the intra-arterial infusion of acetylcholine (ACh), sodium nitroprusside (SNP), and/or the selective endothelin type A (ETA) receptor blocker BQ-123 in 119 obese individuals with MHO (n = 34) or with the MetS (n = 85) and in healthy lean controls (n = 56). ACh and SNP caused a significant vasodilation in both obese and lean participants (all P < 0.001). However, the response to both agents was significantly lower in the obese than in the control group (both P < 0.001). Among the obese participants, the reactivity to ACh was higher in MHO than in MetS patients, whereas the responsiveness to SNP was equally impaired in both groups (P = 0.45). Infusion of BQ-123 significantly increased FBF in obese patients (P < 0001), but not in the lean participants; hence, FBF following ETA receptor blockade was higher in both obese groups than in controls (both P < 0.001). FBF response to BQ-123 was significantly higher in patients with the MetS than in those with MHO (P = 0.007). In conclusion, patients with MHO have abnormal vascular reactivity, although their endothelial dysfunction is less pronounced than in patients with the MetS. These findings indicate that obesity is associated with vascular damage independent of those metabolic abnormalities underlying the MetS. PMID- 26374771 TI - Safety and efficacy of digoxin: systematic review and meta-analysis of observational and controlled trial data. PMID- 26374770 TI - Similar Subgroups Based on Cognitive Performance Parse Heterogeneity in Adults With ADHD and Healthy Controls. AB - OBJECTIVE: To characterize heterogeneity in adults with ADHD we aimed to identify subgroups within the adult ADHD spectrum, which differ in their cognitive profile. METHOD: Neuropsychological data from adults with ADHD ( n = 133) and healthy control participants ( n = 132) were used in a confirmatory factor analysis. The resulting six cognitive factors were correlated across participants to form networks. We used a community detection algorithm to cluster these networks into subgroups. RESULTS: Both the ADHD and control group separated into three profiles that differed in cognitive performance. Profile 1 was characterized by aberrant attention and inhibition, profile 2 by increased delay discounting, and profile 3 by atypical working memory and verbal fluency. CONCLUSION: Our findings suggest that qualitative differences in neuropsychological performance exist in both control and ADHD adult individuals. This extends prior findings in children with and without ADHD and provides a framework to parse participants into well-defined subgroups. PMID- 26374772 TI - Ascariasis of the pancreatic duct. AB - Ascariasis is a common helminthic disease worldwide, although Lithuania and other European countries are not considered endemic areas. The presence of the Ascaris worm in the biliary tree causes choledocholithiasis-like symptoms. We report a case of pancreatic duct ascariasis causing such symptoms. A 73-year-old Lithuanian woman underwent endoscopic retrograde cholangiopancreatography (ERCP) suspecting choledocholithiasis. Contrast injection into the common bile duct demonstrated a slightly dilated biliary tree without any filling defects, and the tail of an Ascaris worm protruding from the opening of the papilla Vater. The worm was captured by a snare but escaped deep into the duct. After a small wirsungotomy the worm was retrieved from the pancreatic duct. The patient received a 150 mg dose of levamisole orally repeated 7 days later and was discharged after complete resolution of symptoms. This first reported sporadic case of pancreatic duct ascariasis in Lithuania was successfully treated with ERCP and Levamisole. PMID- 26374773 TI - Abolished ventilation and perfusion of lung caused by blood clot in the left main bronchus: auto-downregulation of pulmonary arterial blood supply. AB - It is generally assumed that the lungs possess arterial autoregulation associated with bronchial obstruction. A patient with pneumonia and congestive heart failure unexpectedly developed frequent haemoptysis. High-resolution CT and diagnostic CT were performed as well as ventilation/perfusion (V/Q) scintigraphy with single photon emission CT (SPECT)/CT. V/Q SPECT/CT demonstrated abolished ventilation due to obstruction of the left main bronchus and markedly reduced perfusion of the entire left lung, a condition that was completely reversed after removal of a blood clot. We present the first pictorially documented case of hypoxia-induced pulmonary vasoconstriction and flow shift in a main pulmonary artery due to a complete intrinsic obstruction of the ipsilateral main bronchus. The condition is reversible, contingent on being relieved within a few days. PMID- 26374774 TI - An atypical presentation of colonic malignancy: Clostridium septicum aortitis. AB - Clostridium septicum (CS) is a rare organism that accounts for only 1.3% of all clostridial infections. However, its detection is of great clinical significance, as over 80% of cases are associated with malignancy, often occult; the most common primary sites are the ascending colon and caecum, and the most common cause is haematological malignancy. We report a case of a 79-year-old woman, admitted with shortness of breath and left-sided chest pain, who, following subsequent investigations, was found to have CS aortitis. She was further evaluated with CT of the abdomen followed by colonoscopy and biopsy, which revealed adenocarcinoma of the caecum with liver metastasis. The CS aortitis has a reported mortality of 100% if left untreated. Therefore prompt intervention and surgical debridement is recommended. Despite these recommendations, our patient had some delays in her treatment and did not undergo surgical debridement due to frailty. We believe that it is highly unusual for a patient such as ours to have survived both the aortitis and the colonic malignancy, after undergoing endovascular radiological intervention and antibiotic therapy, without surgical debridement. PMID- 26374775 TI - Ileostomy obstruction by ingested apricot stone with clinical-radiological pathological correlation. AB - Patients with stomas often present with bowel obstruction, often secondary to adhesions. This case describes the presentation, investigation and management of a 62-year-old woman with an end ileostomy, who presented to hospital with acute abdominal pain and subacute bowel obstruction. Further questioning revealed the recent ingestion of an apricot stone and this was identified by multimodality imaging as the cause of the luminal obstruction in the distal ileum, just proximal to the stoma. After a failed period of conservative management, examination under anaesthesia was performed and digital extraction attempted, but this was unsuccessful. Rather than surgical stoma revision, endoscopic removal was achieved. The patient improved and was discharged the following day. However, her small bowel obstruction relapsed within 48 h. She was readmitted and underwent stoma revision with no further problems. PMID- 26374776 TI - A unique case of gliomatosis peritonei in a man, following a retroperitoneal teratoma. AB - We present an unusual case of a 56-year-old man presenting with abdominal swelling. Imaging revealed a large abdominal 23 cm cystic mass, which radiologically appeared to be related to the small bowel. There was an attempted surgical removal by the general surgeons. It was histologically confirmed as a retroperitoneal cystic teratoma with immature neural elements with incomplete resection margins. Residual disease was found at re-imaging 3 months later and a further block dissection was performed, with histology confirming recurrence. Thirteen months later, imaging revealed recurrent disease with peritoneal involvement. At laparoscopic exploration, there was peritoneal seeding, and biopsies confirmed a diagnosis of gliomatosis peritonei, secondary to the retroperitoneal teratoma. The patient proceeded to have combination chemotherapy to achieve stable disease on imaging. A month after completion, sadly, the disease progressed; the patient received best supportive care. PMID- 26374777 TI - Dysphagia aortica: a rare cause of dysphagia. AB - Dysphagia is uncommon; however, it is considered a warning symptom, especially in the elderly population, and should prompt consideration of a neoplasm of the oesophagus. Dysphagia aortica is rare and often not considered in clinical practice. It is caused by any abnormality of the aorta that results in dysphagia. These include thoracic aortic aneurysm, aortic dissection and even a tortuous aorta. Our case is of an elderly woman, in her early 70s, with a history of treated colorectal carcinoma and hypertension, who presented with progressive dysphagia to solid foods, which, on investigations, showed a tortuous aorta causing compressions of the oesophagus at multiple levels. She was managed with dietary adjustment and optimal control of blood pressure. PMID- 26374778 TI - Exposure to loud noise, bilateral high-frequency hearing loss and coronary heart disease. AB - OBJECTIVES: Bilateral high-frequency hearing loss is an indicator for chronic exposure to loud noise. This study aimed to examine the association between bilateral high-frequency hearing loss and the presence of coronary heart disease (CHD). METHODS: This study included 5223 participants aged 20-69 years who participated in the audiometry examination of the National Health and Nutrition Examination Survey 1999-2004. Bilateral high-frequency hearing loss was defined as the average high-frequency (3, 4 and 6 kHz) hearing threshold >=25 dB in both ears. CHD was defined as self-reported diagnoses by doctors or other health professionals. RESULTS: Compared with those with normal high-frequency hearing, participants with bilateral high-frequency hearing loss were more likely to have CHD (OR 1.91; 95% CI 1.28 to 2.85) after adjustment for various covariates. This association was particularly strong for currently employed workers who were exposed to loud occupational noise (OR 4.23; 95% CI 1.32 to 13.55). For this subgroup, there was no significant association of CHD with unilateral high frequency hearing loss, and unilateral or bilateral low-frequency hearing loss. Furthermore, there was no significant association of CHD with any types of hearing loss for participants who were not exposed to loud noise. Stratified analyses for participants exposed to loud noise showed that the observed association was particularly strong for those who were less than 50 years of age, less educated and current smokers. CONCLUSIONS: On the basis of an objective indicator for personal chronic exposure to loud noise, this study confirmed that exposure to loud occupational noise is associated with the presence of CHD. PMID- 26374779 TI - Evaluation of the usefulness at national level of the dairy cattle health and production recording systems in Great Britain. AB - The aim of this study was to formally evaluate, qualitatively, the ability of existing recording systems to generate accurate and reliable estimates of the frequency of selected health conditions in the dairy herd of Great Britain. Fifty nine recording systems were identified, of which 36 had their key characteristics defined through a web-based questionnaire. Nineteen of them were further assessed following the SERVAL, a SuRveillance EVALuation framework against a set of 12 attributes: benefit, bias, communication, coverage, data collection, data management, data analysis, data completeness, flexibility, multiple utility, representativeness and stability/sustainability. The evaluated systems showed considerable differences in their coverage, implementation and objectives. There were overlaps in recorded conditions, with Johne's disease, bovine viral diarrhoea, mastitis and lameness being recorded by most of the systems. Selection bias, data ownership and lack of integration of data from different systems appeared to be a key limitation on the future use of existing systems for nationwide monitoring. The results showed that even though the individual systems can provide reliable estimates of dairy health for individual farmers, none of the systems alone could provide accurate and reliable estimates for any of the conditions of interest at national level. PMID- 26374780 TI - Anaesthetic management and complications of balloon valvuloplasty for pulmonic stenosis in dogs. PMID- 26374781 TI - Schmallenberg virus activity in cattle in Switzerland in 2013. PMID- 26374782 TI - Exploration of the power of routine surveillance data to assess the impacts of industry-led badger culling on bovine tuberculosis incidence in cattle herds. AB - In the UK, badgers (Meles meles) are a well-known reservoir of infection, and there has been lively debate about whether badger culling should play a role within the British Government's strategy to control and eventually eradicate tuberculosis (TB) in cattle. The key source of information on the potential for badger culling to reduce cattle TB in high-cattle-TB-incidence areas remains the Randomised Badger Culling Trial (RBCT). In late 2013, two pilot areas were subjected to industry-led badger culls. These culls differed importantly from RBCT culling in that free-ranging as well as cage-trapped badgers were shot, and culling took place over a longer time period. Their impacts will be harder to evaluate because culling was not randomised between comparable areas for subsequent comparisons of culling versus no culling. However, the authors present calculations that explore the power of routine surveillance data to assess the impacts of industry-led badger culling on cattle TB incidence. The rollout of industry-led culling as a component of a national cattle TB control policy would be controversial. The best possible estimates of the effects of such culling on confirmed cattle TB incidence should be made available to inform all stakeholders and policy-makers. PMID- 26374783 TI - Influence of repeated porcine circovirus type 2 vaccination on sows' immune response. PMID- 26374784 TI - Comparison of two cytological methods for detecting pulmonary haemorrhage in horses. PMID- 26374785 TI - How the Non-attending Brain Hears Its Owner's Name. AB - We used functional magnetic resonance imaging to investigate how attended and non attended hearing of a subject's own name (SON) captures his or her attention. It has been reported that SON presentation activates the medial prefrontal cortex (mPFC), which is considered to be the key region for self-recognition. However, it remains unclear whether non-attended SON presentation also activates the mPFC. We hypothesized that an attended SON should activate mPFC more than a non attended SON. To test this hypothesis, we designed an experiment in which we manipulated the task-relevance of SON; in a name-detection task, SON was a target stimulus, whereas in a tone-judgment task, SON was unrelated to the task. In each condition, identical sets of sound stimuli were presented. SON activated mPFC in the name-detection task but not in the tone-judgment task, supporting our hypothesis. In contrast, non-attended SON activated midbrain reticular formation, thalamus, insula, auditory cortex, and precuneus. We interpreted these to be related to low-level, automatic SON detection. Thus, hearing one's own name in a non-attended condition does not primarily engage the mPFC, but recruits a cortico subcortical auditory attention network; this may account for the oft-observed salience of SON. PMID- 26374786 TI - Autism Spectrum Disorder and Epilepsy: Two Sides of the Same Coin? AB - Autism spectrum disorders and epilepsy commonly co-occur. In this review, we consider some unresolved questions regarding the temporal relationship, causal mechanisms, and clinical stratification of this comorbidity, highlighting throughout the interplay between autism spectrum disorder, epilepsy, and intellectual disability. We present data on the clinical characterization of children with autism spectrum disorder and epilepsy, discussing distinctive phenotypes in children with this comorbidity. Although some distinctive clinical features emerge, this comorbidity also informs convergent pathways in genetic variants that cause synaptic dysfunction. We then move beyond diagnostic categorization and consider the extent to which electrophysiology as a quantitative biomarker may help guide efforts in clinical stratification and outcome prediction. Epilepsy, and atypical electrophysiological patterns, in autism spectrum disorder may inform the definition of biologically meaningful subgroups within the spectrum that, in turn, can shed light on potential targets for intervention. PMID- 26374787 TI - Diffuse Intrinsic Pontine Glioma: Time for Cautious Optimism. AB - Diffuse intrinsic pontine glioma is a lethal brain cancer that arises in the pons of children. The median survival for children with diffuse intrinsic pontine glioma is less than 1 year from diagnosis, and no improvement in survival has been realized in more than 30 years. Currently, the standard of care for diffuse intrinsic pontine glioma is focal radiation therapy, which provides only temporary relief. Recent genomic analysis of tumors from biopsies and autopsies, have resulted in the discovery of K27M H3.3/H3.1 mutations in 80% and ACVR1 mutations in 25% of diffuse intrinsic pontine gliomas, providing renewed hope for future success in identifying effective therapies. In addition, as stereotactic tumor biopsies at diagnosis at specialized centers have been demonstrated to be safe, biopsies have now been incorporated into several prospective clinical trials. This article summarizes the epidemiology, clinical presentation, diagnosis, prognosis, molecular genetics, current treatment, and future therapeutic directions for diffuse intrinsic pontine glioma. PMID- 26374788 TI - Toward a trophic theory of species diversity. AB - Efforts to understand the ecological regulation of species diversity via bottom up approaches have failed to yield a consensus theory. Theories based on the alternative of top-down regulation have fared better. Paine's discovery of keystone predation demonstrated that the regulation of diversity via top-down forcing could be simple, strong, and direct, yet ecologists have persistently failed to perceive generality in Paine's result. Removing top predators destabilizes many systems and drives transitions to radically distinct alternative states. These transitions typically involve community reorganization and loss of diversity, implying that top-down forcing is crucial to diversity maintenance. Contrary to the expectations of bottom-up theories, many terrestrial herbivores and mesopredators are capable of sustained order-of-magnitude population increases following release from predation, negating the assumption that populations of primary consumers are resource limited and at or near carrying capacity. Predation sensu lato (to include Janzen-Connell mortality agents) has been shown to promote diversity in a wide range of ecosystems, including rocky intertidal shelves, coral reefs, the nearshore ocean, streams, lakes, temperate and tropical forests, and arctic tundra. The compelling variety of these ecosystems suggests that top-down forcing plays a universal role in regulating diversity. This conclusion is further supported by studies showing that the reduction or absence of predation leads to diversity loss and, in the more dramatic cases, to catastrophic regime change. Here, I expand on the thesis that diversity is maintained by the interaction between predation and competition, such that strong top-down forcing reduces competition, allowing coexistence. PMID- 26374789 TI - Opinion: Measuring development resilience in the world's poorest countries. PMID- 26374791 TI - Histone Acetylation is Involved in Gibberellin-Regulated sodCp Gene Expression in Maize Aleurone Layers. AB - The cereal aleurone layer plays an important role in seed germination, and reactive oxygen species (ROS) in aleurone layers act as crucial signal molecules in this progression. Recent studies have revealed that epigenetic modification is involved in plant development and seed germination. However, little is known about a possible relationship between histone modification and the ROS signaling pathway in cereal aleurone layers during seed germination. Here, we found that the expression of both histone acetyltransferases (HATs) and histone deacetylases (HDACs) was increased gradually during seed germination, accompanied by an increase in global acetylation levels of histones H3 and H4 in maize aleurone layers. The acetylation was found to be promoted by GA(3) and suppressed by ABA. However, when the HDAC inhibitor trichostatin A (TSA) was used, the increased H3K9ac and H4K5ac level correlated with an inhibition of the germination. These results indicated that the overall histone acetylation in the aleurone layers is not required for germination. Similarly these two hormones, GA(3) and ABA, exerted opposed effects on the expression of the ROS-related gene sodCp. Furthermore, chromatin immunoprecipitation experiments showed that the promoter region of the sodCp gene was hyperacetylated during germination, and this acetylation was promoted by GA(3) and inhibited by both ABA and TSA. These results suggested that GA(3)-mediated expression of the sodCp gene in aleurone layers is associated with histone hyperacetylation on the promoter and coding region of this gene, consequently leading to an accumulation of H(2)O(2) which regulated production of alpha-amylase during seed germination. PMID- 26374792 TI - Women's Groups to Improve Maternal and Child Health Outcomes: Different Evidence Paradigms Toward Impact at Scale. PMID- 26374793 TI - Task Sharing Implant Insertion by Community Health Workers: Not Just Can It Work, but How Might It Work Practically and With Impact in the Real World. PMID- 26374794 TI - Institutional Care of Children in Low- and Middle-Income Settings: Challenging the Conventional Wisdom of Oliver Twist. PMID- 26374795 TI - What Does Not Work in Adolescent Sexual and Reproductive Health: A Review of Evidence on Interventions Commonly Accepted as Best Practices. PMID- 26374796 TI - The Demographic Stretch of the Arc of Life: Social and Cultural Changes That Follow the Demographic Transition. PMID- 26374797 TI - WHO Tiered-Effectiveness Counseling Is Rights-Based Family Planning. PMID- 26374798 TI - Care Groups I: An Innovative Community-Based Strategy for Improving Maternal, Neonatal, and Child Health in Resource-Constrained Settings. AB - In view of the slow progress being made in reducing maternal and child mortality in many priority countries, new approaches are urgently needed that can be applied in settings with weak health systems and a scarcity of human resources for health. The Care Group approach uses facilitators, who are a lower-level cadre of paid workers, to work with groups of 12 or so volunteers (the Care Group), and each volunteer is responsible for 10-15 households. The volunteers share messages with the mothers of the households to promote important health behaviors and to use key health services. The Care Groups create a multiplying effect, reaching all households in a community at low cost. This article describes the Care Group approach in more detail, its history, and current NGO experience with implementing the approach across more than 28 countries. A companion article also published in this journal summarizes the evidence on the effectiveness of the Care Group approach. An estimated 1.3 million households almost entirely in rural areas-have been reached using Care Groups, and at least 106,000 volunteers have been trained. The NGOs with experience implementing Care Groups have achieved high population coverage of key health interventions proven to reduce maternal and child deaths. Some of the essential criteria in applying the Care Group approach include: peer-to-peer health promotion (between mothers), selection of volunteers by mothers, limited workload for the volunteers, limited number of volunteers per Care Group, frequent contact between the volunteers and mothers, use of visual teaching tools and participatory behavior change methods, and regular supervision of volunteers. Incorporating Care Groups into ministries of health would help sustain the approach, which would require creating posts for facilitators as well as supervisors. Although not widely known about outside the NGO child survival and food security networks, the Care Group approach deserves broader recognition as a promising alternative to current strategies for delivering key health interventions to remote and underserved communities. PMID- 26374799 TI - Care Groups II: A Summary of the Child Survival Outcomes Achieved Using Volunteer Community Health Workers in Resource-Constrained Settings. AB - The Care Group approach, described in detail in a companion paper in this journal, uses volunteers to convey health promotion messages to their neighbors. This article summarizes the available evidence on the effectiveness of the Care Group approach, drawing on articles published in the peer-reviewed literature as well as data from unpublished but publicly available project evaluations and summary analyses of these evaluations. When implemented by strong international NGOs with adequate funding, Care Groups have been remarkably effective in increasing population coverage of key child survival interventions. There is strong evidence that Care Groups can reduce childhood undernutrition and reduce the prevalence of diarrhea. Finally, evidence from multiple sources, comprising independent assessments of mortality impact, vital events collected by Care Group Volunteers themselves, and analyses using the Lives Saved Tool (LiST), that Care Groups are effective in reducing under-5 mortality. For example, the average decline in under-5 mortality, estimated using LiST, among 8 Care Group projects was 32%. In comparison, among 12 non-Care Group child survival projects, the under-5 mortality declined, on average, by an estimated 11%. Care Group projects cost in the range of US$3-$8 per beneficiary per year. The cost per life saved is in the range of $441-$3,773, and the cost per disability-adjusted life year (DALY) averted is in the range of $15-$126. The Care Group approach, when implemented as described, appears to be highly cost-effective based on internationally accepted criteria. Care Groups represent an important and promising innovative, low-cost approach to increasing the coverage of key child survival interventions in high-mortality, resource-constrained settings. Next steps include further specifying the adjustments needed in government health systems to successfully incorporate the Care Group approach, testing the feasibility of these adjustments and of the effectiveness of Care Groups in pilot programs in government health systems, and finally assessing effectiveness at scale under routine field conditions in government health programs. PMID- 26374800 TI - Task Shifting Provision of Contraceptive Implants to Community Health Extension Workers: Results of Operations Research in Northern Nigeria. AB - BACKGROUND: Contraceptive use remains low in Nigeria, with only 11% of women reporting use of any modern method. Access to long-acting reversible contraceptives (LARCs) is constrained by a severe shortage of human resources. To assess feasibility of task shifting provision of implants, we trained community health extension workers (CHEWs) to insert and remove contraceptive implants in rural communities of Bauchi and Sokoto states in northern Nigeria. METHODS: We conducted 2- to 3-week training sessions for 166 selected CHEWs from 82 facilities in Sokoto state (September 2013) and 84 health facilities in Bauchi state (December 2013). To assess feasibility of the task shifting approach, we conducted operations research using a pretest-posttest design using multiple sources of information, including surveys with 151 trained CHEWs (9% were lost to follow-up) and with 150 family planning clients; facility observations using supply checklists (N = 149); direct observation of counseling provided by CHEWs (N = 144) and of their clinical (N = 113) skills; as well as a review of service statistics (N = 151 health facilities). The endline assessment was conducted 6 months after the training in each state. RESULTS: CHEWs inserted a total of 3,588 implants in 151 health facilities over a period of 6 months, generating 10,088 couple-years of protection (CYP). After practicing on anatomic arm models, most CHEWs achieved competency in implant insertions after insertions with 4-5 actual clients. Clinical observations revealed that CHEWs performed implant insertion tasks correctly 90% of the time or more for nearly all checklist items. The amount of information that CHEWs provided clients increased between baseline and endline, and over 95% of surveyed clients reported being satisfied with CHEWs' services in both surveys. The study found that supervisors not only observed and corrected insertion skills, as needed, during supervisory visits but also encouraged CHEWs to conduct more community mobilization to generate client demand, thereby promoting access to quality services. CHEWs identified a lack of demand in the communities as the major barrier for providing services. CONCLUSION: With adequate training and supportive supervision, CHEWs in northern Nigeria can provide high-quality implant insertion services. If more CHEWs are trained to provide implants and greater community outreach is conducted to generate demand, uptake of LARCs in Nigeria may increase. PMID- 26374801 TI - Prevalence and Incidence of Traumatic Experiences Among Orphans in Institutional and Family-Based Settings in 5 Low- and Middle-Income Countries: A Longitudinal Study. AB - BACKGROUND: Policy makers struggling to protect the 153 million orphaned and separated children (OSC) worldwide need evidence-based research on the burden of potentially traumatic events (PTEs) and the relative risk of PTEs across different types of care settings. METHODS: The Positive Outcomes for Orphans study used a 2-stage, cluster-randomized sampling design to identify 1,357 institution-dwelling and 1,480 family-dwelling orphaned and separated children in 5 low- and middle-income countries (LMICs) in sub-Saharan Africa and Asia. We used the Life Events Checklist developed by the National Center for Posttraumatic Stress Disorder to examine self-reported PTEs among 2,235 OSC ages 10-13 at baseline. We estimated prevalence and incidence during 36-months of follow-up and compared the risk of PTEs across care settings. Data collection began between May 2006 and February 2008, depending on the site. RESULTS: Lifetime prevalence by age 13 of any PTE, excluding loss of a parent, was 91.0% (95% confidence interval (CI) = 85.6, 94.5) in institution-dwelling OSC and 92.4% (95% CI = 90.3, 94.0) in family-dwelling OSC; annual incidence of any PTE was lower in institution dwelling (23.6% [95% CI = 19.4, 28.7]) than family-dwelling OSC (30.0% [95% CI = 28.1, 32.2]). More than half of children in institutions (50.3% [95% CI = 42.5, 58.0]) and in family-based care (54.0% [95% CI = 50.2, 57.7]) had experienced physical or sexual abuse by age 13. Annual incidence of physical or sexual abuse was lower in institution-dwelling (12.9% [95% CI = 9.6, 17.3]) than family dwelling OSC (19.4% [95% CI = 17.7, 21.3]), indicating statistically lower risk in institution-dwelling OSC (risk difference = 6.5% [95% CI = 1.4, 11.7]). CONCLUSION: Prevalence and incidence of PTEs were high among OSC, but contrary to common assumptions, OSC living in institutions did not report more PTEs or more abuse than OSC living with families. Current efforts to reduce the number of institution-dwelling OSC may not reduce incidence of PTEs in this vulnerable population. Protection of children from PTEs should be a primary consideration, regardless of the care setting. PMID- 26374802 TI - Empirically Derived Dehydration Scoring and Decision Tree Models for Children With Diarrhea: Assessment and Internal Validation in a Prospective Cohort Study in Dhaka, Bangladesh. AB - INTRODUCTION: Diarrhea remains one of the most common and most deadly conditions affecting children worldwide. Accurately assessing dehydration status is critical to determining treatment course, yet no clinical diagnostic models for dehydration have been empirically derived and validated for use in resource limited settings. METHODS: In the Dehydration: Assessing Kids Accurately (DHAKA) prospective cohort study, a random sample of children under 5 with acute diarrhea was enrolled between February and June 2014 in Bangladesh. Local nurses assessed children for clinical signs of dehydration on arrival, and then serial weights were obtained as subjects were rehydrated. For each child, the percent weight change with rehydration was used to classify subjects with severe dehydration (>9% weight change), some dehydration (3-9%), or no dehydration (<3%). Clinical variables were then entered into logistic regression and recursive partitioning models to develop the DHAKA Dehydration Score and DHAKA Dehydration Tree, respectively. Models were assessed for their accuracy using the area under their receiver operating characteristic curve (AUC) and for their reliability through repeat clinical exams. Bootstrapping was used to internally validate the models. RESULTS: A total of 850 children were enrolled, with 771 included in the final analysis. Of the 771 children included in the analysis, 11% were classified with severe dehydration, 45% with some dehydration, and 44% with no dehydration. Both the DHAKA Dehydration Score and DHAKA Dehydration Tree had significant AUCs of 0.79 (95% CI = 0.74, 0.84) and 0.76 (95% CI = 0.71, 0.80), respectively, for the diagnosis of severe dehydration. Additionally, the DHAKA Dehydration Score and DHAKA Dehydration Tree had significant positive likelihood ratios of 2.0 (95% CI = 1.8, 2.3) and 2.5 (95% CI = 2.1, 2.8), respectively, and significant negative likelihood ratios of 0.23 (95% CI = 0.13, 0.40) and 0.28 (95% CI = 0.18, 0.44), respectively, for the diagnosis of severe dehydration. Both models demonstrated 90% agreement between independent raters and good reproducibility using bootstrapping. CONCLUSION: This study is the first to empirically derive and internally validate accurate and reliable clinical diagnostic models for dehydration in a resource-limited setting. After external validation, frontline providers may use these new tools to better manage acute diarrhea in children. PMID- 26374803 TI - Improved Reproductive Health Equity Between the Poor and the Rich: An Analysis of Trends in 46 Low- and Middle-Income Countries. AB - While several indicators for reproductive health have improved for entire populations, few analyses are available for trends over time in the gaps between the poor and the rich. This paper tracks improvements in the equitable distribution of reproductive health indicators according to wealth quintiles, especially for contraceptive use, in 46 low- and middle-income countries based on national population-based surveys conducted between 1990 and 2013. It focuses on the gaps between the poorest and richest quintiles in the earliest and latest survey rounds across a number of reproductive health indicators related to family planning, fertility desires, antenatal care, and infant and child mortality, as well as on improvements in the absolute levels of contraceptive use by the poorest quintile. Gap changes were decomposed to show how the gaps can either diminish or grow due to either the bottom or top quintile, or both. In addition, bivariate correlation analysis was conducted to examine the relationship of the gaps, and of contraceptive use by the poor, to national family planning program efforts. Overall, the gaps between the poorest and richest have narrowed, due primarily to faster improvements among the poor than the rich. For example, the gap between the richest and poorest in the modern contraceptive prevalence rate has declined by 25%, from a 20.4 percentage point difference to a 15.4 point difference. And the gap has decreased more where family planning programs have been stronger. Across most of 18 other reproductive health indicators, the gaps have also been narrowing. For instance, the poor-rich gap for antenatal care decreased by over a third, from a difference of 30.7 percentage points to 19.6 percentage points. Gaps in infant and child mortality also have declined by about one-third. The pattern for contraceptive use in sub-Saharan Africa, however, has been mixed, with the gap actually increasing in some countries with strong programs. This disparity may largely reflect that family planning in the region is generally at an earlier stage in its history, and so programs may initially be reaching better-off clients, especially in urban areas. To promote additional equity, programs should emphasize efforts to increase access to voluntary family planning services to the least well-off, including those in rural and peri-urban areas. PMID- 26374804 TI - Regulatory Monitoring of Fortified Foods: Identifying Barriers and Good Practices. AB - While fortification of staple foods and condiments has gained enormous global traction, poor performance persists throughout many aspects of implementation, most notably around the critical element of regulatory monitoring, which is essential for ensuring foods meet national fortification standards. Where coverage of fortified foods is high, limited nutritional impact of fortification programs largely exists due to regulatory monitoring that insufficiently identifies and holds producers accountable for underfortified products. Based on quality assurance data from 20 national fortification programs in 12 countries, we estimate that less than half of the samples are adequately fortified against relevant national standards. In this paper, we outline key findings from a literature review, key informant interviews with 11 fortification experts, and semi-quantitative surveys with 39 individuals from regulatory agencies and the food fortification industry in 17 countries on the perceived effectiveness of regulatory monitoring systems and barriers to compliance against national fortification standards. Findings highlight that regulatory agencies and industry disagree on the value that enforcement mechanisms have in ensuring compliance against standards. Perceived political risk of enforcement and poorly resourced inspectorate capacity appear to adversely reinforce each other within an environment of unclear legislation to create a major hurdle for improving overall compliance of fortification programs against national standards. Budget constraints affect the ability of regulatory agencies to create a well-trained inspector cadre and improve the detection and enforcement of non-compliant and underfortified products. Recommendations to improve fortification compliance include improving technical capacity; ensuring sustained leadership, accountability, and funding in both the private and the public sectors; and removing political barriers to ensure consistent detection of underfortified products and enforcement of applicable fortification standards. Only by taking concrete steps to improve the entire regulatory system that is built on a cooperative working relationship between regulatory agencies and food producers will a nutrition strategy that uses fortification see its intended health effects. PMID- 26374805 TI - Estimating Contraceptive Prevalence Using Logistics Data for Short-Acting Methods: Analysis Across 30 Countries. AB - BACKGROUND: Contraceptive prevalence rate (CPR) is a vital indicator used by country governments, international donors, and other stakeholders for measuring progress in family planning programs against country targets and global initiatives as well as for estimating health outcomes. Because of the need for more frequent CPR estimates than population-based surveys currently provide, alternative approaches for estimating CPRs are being explored, including using contraceptive logistics data. METHODS: Using data from the Demographic and Health Surveys (DHS) in 30 countries, population data from the United States Census Bureau International Database, and logistics data from the Procurement Planning and Monitoring Report (PPMR) and the Pipeline Monitoring and Procurement Planning System (PipeLine), we developed and evaluated 3 models to generate country-level, public-sector contraceptive prevalence estimates for injectable contraceptives, oral contraceptives, and male condoms. Models included: direct estimation through existing couple-years of protection (CYP) conversion factors, bivariate linear regression, and multivariate linear regression. Model evaluation consisted of comparing the referent DHS prevalence rates for each short-acting method with the model-generated prevalence rate using multiple metrics, including mean absolute error and proportion of countries where the modeled prevalence rate for each method was within 1, 2, or 5 percentage points of the DHS referent value. RESULTS: For the methods studied, family planning use estimates from public sector logistics data were correlated with those from the DHS, validating the quality and accuracy of current public-sector logistics data. Logistics data for oral and injectable contraceptives were significantly associated (P<.05) with the referent DHS values for both bivariate and multivariate models. For condoms, however, that association was only significant for the bivariate model. With the exception of the CYP-based model for condoms, models were able to estimate public sector prevalence rates for each short-acting method to within 2 percentage points in at least 85% of countries. CONCLUSIONS: Public-sector contraceptive logistics data are strongly correlated with public-sector prevalence rates for short-acting methods, demonstrating the quality of current logistics data and their ability to provide relatively accurate prevalence estimates. The models provide a starting point for generating interim estimates of contraceptive use when timely survey data are unavailable. All models except the condoms CYP model performed well; the regression models were most accurate but the CYP model offers the simplest calculation method. Future work extending the research to other modern methods, relating subnational logistics data with prevalence rates, and tracking that relationship over time is needed. PMID- 26374806 TI - The Astronomy of Africa's Health Systems Literature During the MDG Era: Where Are the Systems Clusters? AB - Growing international concern about the need for improved health systems in Africa has catalyzed an expansion of the health systems literature. This review applies a bibliometric procedure to analyze the acceleration of scientific writing on this theme. We focus on research published during the Millennium Development Goal (MDG) era between 1990 and 2014, reporting findings from a systematic review of a database comprised of 17,655 articles about health systems themes from sub-Saharan African countries or subregions. Using bibliometric tools for co-word textual analysis, we analyzed the incidence and associations of keywords and phrases to generate and visualize topical foci on health systems as clusters of themes, much in the manner that astronomers represent groupings of stars as galaxies of celestial entities. The association of keywords defines their relative position, with the size of images weighted by the relative frequency of terms. Sets of associated keywords are arrayed as stars that cluster as "galaxies" of concepts in the knowledge universe represented by health systems research from sub-Saharan Africa. Results show that health systems research is dominated by literature on diseases and categorical systems research topics, rather than on systems science that cuts across diseases or specific systemic themes. Systems research is highly developed in South Africa but relatively uncommon elsewhere in the region. "Black holes" are identified by searching for terms in our keyword library related to terms in widely cited reviews of health systems. Results identify several themes that are unexpectedly uncommon in the country-specific health systems literature. This includes research on the processes of achieving systems change, the health impact of systems strengthening, processes that explain the systems determinants of health outcomes, or systematic study of organizational dysfunction and ways to improve system performance. Research quantifying the relationship of governance indicators to health systems strengthening is nearly absent from the literature. Long-term experimental studies and statistically rigorous research on cross cutting themes of health systems strengthening are rare. Studies of organizational malaise or corruption are virtually absent. Trend analysis shows the emergence of organizational research on specific priority diseases, such as on HIV/AIDS, malaria, and tuberculosis, but portrays a lack of focus on integrated systems research on the general burden of disease. If health systems in Africa are to be strengthened, then organizational change research must be a more concerted focus in the future than has been the case in the past. PMID- 26374807 TI - Covering the Last Kilometer: Using GIS to Scale-Up Voluntary Medical Male Circumcision Services in Iringa and Njombe Regions, Tanzania. AB - BACKGROUND: Based on the established protective effect of voluntary medical male circumcision (VMMC) in reducing female-to-male HIV transmission, Tanzania's Ministry of Health and Social Welfare (MOHSW) embarked on the scale-up of VMMC services in 2009. The Maternal and Child Health Integrated Project (MCHIP) supported the MOHSW to roll out VMMC services in Iringa and Njombe, 2 regions of Tanzania with among the highest HIV and lowest circumcision prevalence. With ambitious targets of reaching 264,990 males aged 10-34 years with VMMC in 5 years, efficient and innovative program approaches were necessary. PROGRAM DESCRIPTION: Outreach campaigns, in which mobile teams set up temporary services in facilities or non-facility settings, are used to reach lesser-served areas with VMMC. In 2012, MCHIP began using geographic information systems (GIS) to strategically plan the location of outreach campaigns. MCHIP gathered geocoded data on variables such as roads, road conditions, catchment population, staffing, and infrastructure for every health facility in Iringa and Njombe. These data were uploaded to a central database and overlaid with various demographic and service delivery data in order to identify the VMMC needs of the 2 regions. FINDINGS: MCHIP used the interactive digital maps as decision-making tools to extend mobile VMMC outreach to "the last kilometer." As of September 2014, the MOHSW with MCHIP support provided VMMC to 267,917 men, 259,144 of whom were men were aged 10-34 years, an achievement of 98% of the target of eligible males in Iringa and Njombe. The project reached substantially more men through rural dispensaries and non-health care facilities each successive year after GIS was introduced in 2012, jumping from 48% of VMMCs performed in rural areas in fiscal year 2011 to 88% in fiscal year 2012 and to 93% by the end of the project in 2014. CONCLUSION: GIS was an effective tool for making strategic decisions about where to prioritize VMMC service delivery, particularly for mobile and outreach services. Donors may want to consider funding mapping initiatives that support numerous interventions across implementing partners to spread initial start-up costs. PMID- 26374808 TI - Remote Sensing of Vital Signs: A Wearable, Wireless "Band-Aid" Sensor With Personalized Analytics for Improved Ebola Patient Care and Worker Safety. PMID- 26374809 TI - Level 2 Observational Studies: A Practical Alternative to Randomized Trials in Plastic Surgery. PMID- 26374810 TI - Does a Deep-Plane Facelift Restore Malar Volume Without Simultaneous Fat Injection? PMID- 26374811 TI - Response to "Does a Deep-Plane Facelift Restore Malar Volume Without Simultaneous Fat Injection?". PMID- 26374812 TI - Power-assisted gluteal augmentation: a new technique for sculpting, harvesting, and transferring fat. AB - BACKGROUND: A simple and reproducible surgical technique for gluteal shaping and augmentation with autologous fat is needed. OBJECTIVES: The authors describe a novel approach to large-volume gluteal augmentation that combines power-assisted liposculpting and fat harvesting of the zones around the buttock with autologous fat transfer. METHODS: One hundred ten patients who underwent gluteal augmentation were evaluated in a prospective study. Liposculpting and fat harvesting were performed with power-assisted liposuction. Fat then was transferred to the gluteal region with simultaneous power-assisted vibration and tunnelization. A questionnaire to assess patient satisfaction was administered at 6 months postoperatively. RESULTS: The mean body mass index of the patients was 30 kg/m(2) (range, 26-36 kg/m(2)). Liposuction volumes ranged from 1400 to 5000 mL, and injection volumes ranged from 300 to 900 mL per side for each session. Operating times ranged from 60 to 120 minutes. Patients were monitored for an average of 20 months (range 12-48 months). Complications included a burning sensation in 5 of 110 patients (4.5%), persistent swelling in the lower back in 3 patients (2.7%), and a mild infection in 1 patient (0.9%). CONCLUSIONS: Power assisted gluteal augmentation with autologous fat is an efficient, safe, and reproducible procedure that produces an aesthetically pleasing gluteal projection and contour. LEVEL OF EVIDENCE: 4 Therapeutic. PMID- 26374813 TI - Response to "Level 2 Observational Studies: A Practical Alternative to Randomized Trials in Plastic Surgery". PMID- 26374815 TI - Editorial commentary: the effect of Tdap vaccination of pregnant women on the subsequent antibody responses of their infants. PMID- 26374814 TI - Prostaglandin-Associated Periorbital Lipodystrophy in Cosmetic Eyelid Surgery: A Novel Cause of Facial Asymmetry. AB - A 70-year-old woman presented to our practice with profound ptosis of the left upper eyelid and notable asymmetry of the periocular area. On examination, she was noted to have significant atrophy of the periocular tissues on the left side, with lower eyelid retraction. These features were present but less severe on the right side. Upon further questioning, she stated that she had cataract surgery on the left side that was complicated by a high intraocular pressure and required subsequent secondary surgery. She had taken a prostaglandin eyedrop for many months after her cataract surgery to keep the eye pressure low. Recently, a newly recognized adverse effect of prostaglandin eyedrops has been described in the ophthalmic literature in which patients develop periorbital lipodystrophy. This case emphasizes that this may occur unilaterally in patients taking the eyedrop in only one eye, and should be recognized prior to considering functional and aesthetic surgery of the periocular area. PMID- 26374816 TI - Antibody responses after primary immunization in infants born to women receiving a pertussis-containing vaccine during pregnancy: single arm observational study with a historical comparator. AB - INTRODUCTION: In England, antenatal pertussis immunization using a tetanus/low dose diphtheria/5-component acellular-pertussis/inactivated-polio (TdaP5/IPV) vaccine was introduced in October 2012. We assessed infant responses to antigens in the maternal vaccine and to those conjugated to tetanus (TT) or the diphtheria toxin variant, CRM. METHODS: Infants of 141 TdaP5/IPV-vaccinated mothers in Southern England immunized with DTaP5/IPV/Haemophilus influenzae b (Hib-TT) vaccine at 2-3-4 months, 13-valent pneumococcal vaccine (PCV13, CRM-conjugated) at 2-4 months and 1 or 2 meningococcal C vaccine (MCC-CRM- or MCC-TT) doses at 3 4 months had blood samples taken at 2 and/or 5 months of age. RESULTS: Antibody responses to pertussis toxin (PT), filamentous hemagglutinin (FHA), fimbriae 2 + 3 (FIMs), diphtheria, tetanus, Hib, MCC and PCV13 serotypes were compared to responses in a historical cohort of 246 infants born to mothers not vaccinated in pregnancy. Infants had high pertussis antibody concentrations pre-immunization but only PT antibodies increased post-immunization (fold-change, 2.64; 95% confidence interval [CI], 2.12-3.30; P < .001), whereas FHA antibodies fell (fold change, 0.56; 95% CI, .48-.65; P < .001). Compared with infants of unvaccinated mothers, PT, FHA, and FIMs antibodies were lower post-vaccination, with fold differences of 0.67 (0.58-0.77; P < .001), 0.62 (0.54-0.71; P < .001) and 0.51 (0.42-0.62; P < .001), respectively. Antibodies to diphtheria and some CRM conjugated antigens were also lower, although most infants achieved protective thresholds; antibodies to tetanus and Hib were higher. CONCLUSIONS: Antenatal pertussis immunization results in high infant pre-immunization antibody concentrations, but blunts subsequent responses to pertussis vaccine and some CRM conjugated antigens. In countries with no pertussis booster until school age, continued monitoring of protection against pertussis is essential. PMID- 26374817 TI - [How should obesity be measured in childhood?[Editorial]]. PMID- 26374818 TI - [Increasing tourism--a challenge for health care[Editorial]]. PMID- 26374819 TI - [Importance of waist circumference measurements when following children with obesity: Serious abnormalities in blood values of Iceandic children with obesity]. AB - INTRODUCTION: Childhood obesity is a growing health problem worldwide. Body mass index (BMI) has been used as the main measurement of obesity for years but its quality for children has been questioned. In 2011 the Health School was formed at the Childrens Medical Center at Landspitali University Hospital for treatment of obese children and their families. The aim of this study was to find the best predictor of blood test abnormalities and to get a clear picture of abnormalities in blood values in the group of obese children referred to the Health School. METHODS: All children referred to the Health School from January 1st 2011 until March 15th 2013 were retrospectively studied (n=181). Information was gathered on height, weight, BMI, waist circumference and available blood variables. RESULTS: Abnormal blood values were found in 54 cases (47%). Of the children where information was available, four (4%) had Non-Alchoholic Fatty Liver Disease (NAFLD) and 28 (28%) had a raised fasting insulin levels whereof 8 (8%) needed treatment. One child had both NAFLD and raised fasting insulin. CONCLUSION: Abnormal blood values are common in obese children. Waist circumference appears to have a better predictive value of these abnormalities than BMI-SDS. Waist circumference could be used to screen for children who need physician supervision because of risk of metabolic disorders. Waist circumference adds important information to the risk assessment of obese children. This study emphasises the importance of care givers measuring waist circumference in obese children. PMID- 26374820 TI - [Effects of rehabilitation on functional capacity, obesity and health behavior, among cardiac patients with DM2]. AB - OBJECTIVE: Present study examines the prevalence of type 2 diabetes (DM2) in patients attending cardiac rehabilitation (CR) compared to the general population utilising data from the Icelandic Heart Association population study. The study also examined the efficacy of CR for promoting health behaviors. MATERIAL AND METHODS: A prospective study among DM2 patients attending CR at Reykjalundur Rehabilitation centre. The DM2 group was compared to other cardiac patients, with respect to obesity and exercise capacity at the beginning and end of 4-6 weeks of CR. Additionally, in the DM2 group, weight, smoking cessation, physical activity and walking capacity were assessed at 3 and 6 months follow-ups. RESULTS: The prevalence of DM2 was 2-4 times higher in CR participants than in the general population. Compared to other CR participants, the DM2 group was heavier, with increased waist circumference and less exercise capacity. During the CR both groups lost weight and waist circumference decreased to similar extent, but the exercise capacity increased less in the DM2 group. In follow up after 6 months the DM2 group's weight and glucose values were back to same level as before CR, but waist circumference was still decreased and they retained increased physical activity and walking capacity. CONCLUSION: DM2 is more prevalent among patients in cardiac rehabilitation than in the general population. The DM2 group was more obese, had lower exercise capacity and responded somewhat less to CR than other cardiac patients. Follow up after 6 months did however show that they continued their regular exercise and walking capacity was still retained. PMID- 26374821 TI - [Skin eruption and itching after travel to Asia--a case report]. AB - One of the more common reasons patients seek medical advice after traveling in tropical countries are skin eruptions. Here we describe two cases of individuals who, after traveling to south east Asia, developed a skin eruption later diagnosed as cutaneous larva migrans. This particular skin condition is common among travelers to countries where the hookworm responsible is endemic. The diagnosis is based on travel history and clinical examination. The patients were treated with albendazole with good results and complete resolution of the symptoms. PMID- 26374822 TI - Changing nomenclature for PBC: from 'cirrhosis' to 'cholangitis'. PMID- 26374824 TI - Three new species of Pseudodactylogyrus (Monogenea: Pseudodactylogyridae) from Australian eels. AB - Three species of Pseudodactylogyrus Gusev, 1965 (Monogenea: Pseudodactylogyridae) were collected from the gills of Anguilla reinhardtii Steindachner and A. australis Richardson from several localities in Australia and eels imported to Japan from Australia. Pseudodactylogyrus gusevi sp. n. from A. reinhardtii (type host) and A. australis in Queensland, Australia is most similar to P. bini (Kikuchi, 1929), but can be differentiated by the shorter male copulatory tube, heavy sclerotisation of the vaginal tube and the presence of a small projection of the supplementary piece of the hamulus. Pseudodactylogyrus rohdei sp. n. from A. australis (type host) in Queensland, Australia is most similar to P. anguillae (Yin et Sproston, 1948), but differs in the possession of a longer cement gland and the presence of a small projection on the supplementary piece of the hamulus. Pseudodactylogyrus bini sensu Gusev, 1965 and P. anguillae sensu Gusev, 1965 are synonymised with P. gusevi sp. n. and P. rohdei sp. n., respectively. Pseudodactylogyrus mundayi sp. n. from A. australis, originating in Tasmania, Australia and sent alive to Japan, is most similar to P. kamegaii Iwashita, Hirata et Ogawa, 2002, from which it can be discriminated by the shorter male copulatory tube and the shorter vaginal tube. Dactylogyrus bialatus Wu, Wang et Jian, 1988 from Synechogobius ommaturus (Richardson) (Gobiidae) is transferred to Pseudodactylogyrus as P. bialatus comb. n. A phylogenetic tree based on the ITS2 region of six species of Pseudodactylogyrus including P. gusevi and P. mundayi shows that P. haze from a goby diverged first, and that species from eels are monophyletic, forming three lineages differing by their zoogeographical distribution. With the three new species and one new combination proposed in this paper, Pseudodactylogyrus is now comprised of eight species infecting anguillid and gobiid fish, and a key to species is presented. PMID- 26374823 TI - The generation and analyses of a novel combination of recombinant adenovirus vaccines targeting three tumor antigens as an immunotherapeutic. AB - Phenotypic heterogeneity of human carcinoma lesions, including heterogeneity in expression of tumor-associated antigens (TAAs), is a well-established phenomenon. Carcinoembryonic antigen (CEA), MUC1, and brachyury are diverse TAAs, each of which is expressed on a wide range of human tumors. We have previously reported on a novel adenovirus serotype 5 (Ad5) vector gene delivery platform (Ad5 [E1-, E2b-]) in which regions of the early 1 (E1), early 2 (E2b), and early 3 (E3) genes have been deleted. The unique deletions in this platform result in a dramatic decrease in late gene expression, leading to a marked reduction in host immune response to the vector. Ad5 [E1-, E2b-]-CEA vaccine (ETBX-011) has been employed in clinical studies as an active vaccine to induce immune responses to CEA in metastatic colorectal cancer patients. We report here the development of novel recombinant Ad5 [E1-, E2b-]-brachyury and-MUC1 vaccine constructs, each capable of activating antigen-specific human T cells in vitro and inducing antigen-specific CD4+ and CD8+ T cells in vaccinated mice. We also describe the use of a combination of the three vaccines (designated Tri-Ad5) of Ad5 [E1-, E2b ]-CEA, Ad5 [E1-, E2b-]-brachyury and Ad5 [E1-, E2b-]-MUC1, and demonstrate that there is minimal to no "antigenic competition" in in vitro studies of human dendritic cells, or in murine vaccination studies. The studies reported herein support the rationale for the application of Tri-Ad5 as a therapeutic modality to induce immune responses to a diverse range of human TAAs for potential clinical studies. PMID- 26374827 TI - Correlative Light and Scanning Electron Microscopy for Observing the Three Dimensional Ultrastructure of Membranous Cell Organelles in Relation to Their Molecular Components. AB - Although the osmium maceration method has been used to observe three-dimensional (3D) structures of membranous cell organelles with scanning electron microscopy (SEM), the use of osmium tetroxide for membrane fixation and the removal of cytosolic soluble proteins largely impairs the antigenicity of molecules in the specimens. In the present study, we developed a novel method to combine cryosectioning with the maceration method for correlative immunocytochemical analysis. We first immunocytochemically stained a semi-thin cryosection cut from a pituitary tissue block with a cryo-ultramicrotome, according to the Tokuyasu method, before preparing an osmium-macerated specimen from the remaining tissue block. Correlative microscopy was performed by observing the same area between the immunostained section and the adjacent face of the tissue block. Using this correlative method, we could accurately identify the gonadotropes of pituitary glands in various experimental conditions with SEM. At 4 weeks after castration, dilated cisternae of rough endoplasmic reticulum (RER) were distributed throughout the cytoplasm. On the other hand, an extremely dilated cisterna of the RER occupied the large region of the cytoplasm at 12 weeks after castration. This novel method has the potential to analyze the relationship between the distribution of functional molecules and the 3D ultrastructure in different composite tissues. PMID- 26374825 TI - Characterization of Autosomal Dominant Hypercholesterolemia Caused by PCSK9 Gain of Function Mutations and Its Specific Treatment With Alirocumab, a PCSK9 Monoclonal Antibody. AB - BACKGROUND: Patients with PCSK9 gene gain of function (GOF) mutations have a rare form of autosomal dominant hypercholesterolemia. However, data examining their clinical characteristics and geographic distribution are lacking. Furthermore, no randomized treatment study in this population has been reported. METHODS AND RESULTS: We compiled clinical characteristics of PCSK9 GOF mutation carriers in a multinational retrospective, cross-sectional, observational study. We then performed a randomized placebo-phase, double-blind study of alirocumab 150 mg administered subcutaneously every 2 weeks to 13 patients representing 4 different PCSK9 GOF mutations with low-density lipoprotein cholesterol (LDL-C) >=70 mg/dL on their current lipid-lowering therapies at baseline. Observational study: among 164 patients, 16 different PCSK9 GOF mutations distributed throughout the gene were associated with varying severity of untreated LDL-C levels. Coronary artery disease was common (33%; average age of onset, 49.4 years), and untreated LDL-C concentrations were higher compared with matched carriers of mutations in the LDLR (n=2126) or apolipoprotein B (n=470) genes. Intervention study: in PCSK9 GOF mutation patients randomly assigned to receive alirocumab, mean percent reduction in LDL-C at 2 weeks was 62.5% (P<0.0001) from baseline, 53.7% compared with placebo-treated PCSK9 GOF mutation patients (P=0.0009; primary end point). After all subjects received 8 weeks of alirocumab treatment, LDL-C was reduced by 73% from baseline (P<0.0001). CONCLUSIONS: PCSK9 GOF mutation carriers have elevated LDL-C levels and are at high risk of premature cardiovascular disease. Alirocumab, a PCSK9 antibody, markedly lowers LDL-C levels and seems to be well tolerated in these patients. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique Identifier: NCT01604824. PMID- 26374826 TI - Synthesis of an Endogenous Steroidal Na Pump Inhibitor Marinobufagenin, Implicated in Human Cardiovascular Diseases, Is Initiated by CYP27A1 via Bile Acid Pathway. AB - BACKGROUND: The bioactive steroid, marinobufagenin, is an endogenous Na/K-ATPase bufadienolide inhibitor that is synthesized by adrenocortical and placental cells. Marinobufagenin binding to Na/K-ATPase initiates profibrotic cell signaling, and heightened marinobufagenin levels are implicated in the pathogenesis of hypertension, preeclampsia, and chronic kidney disease. Steroids are derived from cholesterol through the traditional steroidogenesis pathway initiated by enzyme CYP11A1, and via the acidic bile acid pathway, which is controlled by enzyme CYP27A1. The mechanism of marinobufagenin biosynthesis in mammals, however, remains unknown. METHODS AND RESULTS: Here, we show that post transcriptional silencing of the CYP27A1 gene in human trophoblast and rat adrenocortical cells reduced the expression of CYP27A1 mRNA by 70%, reduced total bile acids 2-fold, and marinobufagenin levels by 67% when compared with nontreated cells or cells transfected with nontargeting siRNA. In contrast, silencing of the CYP11A1 gene did not affect marinobufagenin production in either cell culture, but suppressed production of progesterone 2-fold in human trophoblast cells and of corticosterone by 90% in rat adrenocortical cells when compared with cells transfected with nontargeting siRNA. In vivo, in a high-salt administration experiment, male and female Dahl salt-sensitive rats became hypertensive after 4 weeks on a high-NaCl diet, their plasma marinobufagenin levels doubled, and adrenocortical CYP27A1 mRNA and protein increased 1.6-fold and 2.0-fold. CONCLUSIONS: Therefore, the endogenous steroidal Na/K-ATPase inhibitor, marinobufagenin, is synthesized in mammalian placenta and adrenal cortex from cholesterol through the novel acidic bile acid pathway. These findings will help to understand the role of marinobufagenin in highly prevalent human cardiovascular diseases. PMID- 26374828 TI - Immunocytochemical Evidence for Golgi Vesicle Involvement in Milk Fat Globule Secretion. AB - The exact mechanism of secretion of the milk fat globule (MFG) from the mammary secretory cell is still controversial. We have previously suggested close involvement of Golgi vesicles in this process. This paper provides direct immunocytochemical evidence that butyrophilin is present in the Golgi stack and vesicles in ovine and caprine mammary glands. We suggest that it is the butyrophilin in the Golgi vesicle membrane that forms the specific association with the adipophilin on the lipid surface in the cytoplasm. Exocytosis of the associated Golgi vesicle will then initiate the process of MFG secretion. Further exocytosis of associated Golgi vesicles will continue and complete the process. Areas of the plasmalemma that have butyrophilin delivered by previous non-lipid associated Golgi exocytoses may also contribute to the process of forming the milk fat globule membrane (MFGM). PMID- 26374829 TI - Identification of CEACAM5 as a Biomarker for Prewarning and Prognosis in Gastric Cancer. AB - MGd1, a monoclonal antibody raised against gastric cancer cells, possesses a high degree of specificity for gastric cancer (GC). Here we identified that the antigen of MGd1 is CEACAM5, and used MGd1 to investigate the expression of CEACAM5 in non-GC and GC tissues (N=643), as a biomarker for prewarning and prognosis. The expression of CEACAM5 was detected by immunohistochemistry in numerous tissues; its clinicopathological correlation was statistically analyzed. CEACAM5 expression was increased progressively from normal gastric mucosa to chronic atrophic gastritis, intestinal metaplasia, dysplasia and finally to GC (p<0.05). In gastric precancerous lesions (intestinal metaplasia and dysplasia), CEACAM5-positive patients had a higher risk of developing GC as compared with CEACAM5-negative patients (OR = 12.68, p<0.001). Besides, CEACAM5 was found positively correlated with invasion depth of gastric adenocarcinoma (p<0.001). In survival analysis, CEACAM5 was demonstrated to be an independent prognostic predictor for patients with GC of clinical stage IIIA/IV (p=0.033). Our results demonstrate that CEACAM5 is a promising biomarker for GC prewarning and prognostic evaluation. PMID- 26374832 TI - Association between toxocariasis and cognitive function in young to middle-aged adults. AB - The ascarid nematodes Toxocara canis (Werner, 1782) and Toxocara cati (Schrank, 1788) may infect humans resulting in toxocariasis. A prior study associated species of Toxocara Stiles, 1905 with cognitive deficits in children. To determine if a similar association between toxocariasis and cognition exists in adults, we analysed a large dataset from the United States' Center for Disease Control's National Health and Nutrition Examination Survey. We used linear regression and multivariate models to examine the association between toxocariasis as assessed by the presence of anti-Toxocara IgG antibodies and three measures of cognitive function - simple reaction time (SRT), symbol-digit substitution (SDS) and serial-digit learning (SDL) in 4 279 adults aged 21 to 59 years. Toxocara seroprevalence did not vary with age or blood-lead concentration but did vary with gender, ethnicity, educational attainment and poverty-to-income ratio. Controlling for gender, age, blood-lead concentration, educational attainment, ethnic background and the poverty-to-income ratio, we found that toxocariasis predicted worse performance on the SDS but not on the SRT or the SDL. Moreover, there were significant interactions between toxocariasis and age, gender and educational attainment. In conclusion, toxocariasis appears to be associated with decreased cognitive function. Interactions between toxocariasis and gender, age and educational attainment further suggest that certain groups may be more susceptible than others to the cognitive dysfunction associated with toxocariasis in adults. PMID- 26374830 TI - Endothelial Fas-Ligand in Inflammatory Bowel Diseases and in Acute Appendicitis. AB - Fas-mediated induction of apoptosis is a major factor in the selection of lymphocytes and downregulation of immunological processes. In the present study, we have assessed endothelial Fas-ligand (FasL) expression in normal human ileum, appendix, and colon, and compared the expression levels with that in inflammatory bowel disease and in acute appendicitis. In a normal appendix, endothelial FasL levels were constant in almost half of the mucosal vessels; but, in the normal ileum and colon, endothelial FasL was practically restricted to areas in close proximity to lymphatic follicles, and was expressed mainly in the submucosal aspect of the follicles in the vessels with high endothelium. In samples from subjects with either Crohn's disease or ulcerative colitis, the extent of endothelial FasL expression was elevated in the submucosa and associated with an elevated number of lymphoid follicles. In inflammatory bowel disease, ulcers and areas with a high density of mononuclear cells expressing FasL also showed an elevated density of blood vessels with endothelial FasL expression. Although the function of endothelial FasL remains unclear, such a specific expression pattern suggests that endothelial FasL expression has a role in the regulation of lymphocyte access to the peripheral lymphoid tissues, including the intestinal mucosa. PMID- 26374831 TI - Expression of Carcinoembryonic Cell Adhesion Molecule 6 and Alveolar Epithelial Cell Markers in Lungs of Human Infants with Chronic Lung Disease. AB - The membrane protein carcinoembryonic antigen cell adhesion molecule (CEACAM6) is expressed in the epithelium of various tissues, participating in innate immune defense, cell proliferation and differentiation, with overexpression in gastrointestinal tract, pancreatic and lung tumors. It is developmentally and hormonally regulated in fetal human lung, with an apparent increased production in preterm infants with respiratory failure. To further examine the expression and cell localization of CEACAM6, we performed immunohistochemical and biochemical studies in lung specimens from infants with and without chronic lung disease. CEACAM6 protein and mRNA were increased ~4-fold in lungs from infants with chronic lung disease as compared with controls. By immunostaining, CEACAM6 expression was markedly increased in the lung parenchyma of infants and children with a variety of chronic lung disorders, localizing to hyperplastic epithelial cells with a ~7-fold elevated proliferative rate by PCNA staining. Some of these cells also co-expressed membrane markers of both type I and type II cells, which is not observed in normal postnatal lung, suggesting they are transitional epithelial cells. We suggest that CEACAM6 is both a marker of lung epithelial progenitor cells and a contributor to the proliferative response after injury due to its anti-apoptotic and cell adhesive properties. PMID- 26374833 TI - Ketoacid Supplementation Partially Improves Metabolic Parameters in Patients on Peritoneal Dialysis. AB - ? BACKGROUND: A low protein diet supplemented with ketoacids has been shown to improve the metabolic profile, including insulin resistance, in patients with chronic kidney disease (CKD), but whether ketoacids alone exert similar effects is unknown. In this prospective randomized controlled trial, we aimed to evaluate the effects of ketoacid supplementation on insulin resistance, systemic inflammation, oxidative stress and endothelial dysfunction among 100 CKD patients undergoing peritoneal dialysis (PD). ? METHODS: Patients from one Chinese PD center were randomly assigned to take ketoacids (12 tablets per day) (n = 50) versus a control group (n = 50) for 6 months in an open-label parallelarm design. Daily protein intake of 0.8 - 1.2 g/kg/d and daily energy intake of 25 - 35 kcal/kg/d was prescribed to both groups. Insulin resistance was evaluated using homeostatic model assessment (HOMA-IR) index as the primary outcome. We assessed systemic inflammation using high-sensitive C-reactive protein (hs-CRP) and interleukin-6 (IL-6), oxidative stress using plasma oxidized low density lipoprotein (oxLDL), adipokines using leptin and adiponectin and endothelial dysfunction using serum soluble intercellular adhesion molecule-1 (sICAM) and soluble vascular adhesion molecule-1 (sVCAM) as secondary outcomes. ? RESULTS: There were no significant differences in baseline characteristics between the 2 groups except a slightly higher age in patients assigned to the intervention. A total of 89% of participants completed the 6-month intervention. There was no significant difference in the change of HOMA-IR values from baseline between groups after adjusting for baseline age, gender, body mass index and HOMA-IR. For secondary outcomes, hs-CRP varied significantly between groups (p = 0.02), increasing over time for the control group while remaining stable for the ketoacid group. Similarly, the leptin/adiponectin ratio (LAR) differed between groups (p < 0.001), remaining stable in the ketoacid group but increasing in the control group. ? CONCLUSION: Ketoacid therapy administered for 6 months had no effect on HOMA-IR but resulted in improvements in hs-CRP and LAR, suggesting metabolic benefit. Future studies are needed to confirm these results and any potential benefit in vascular health of PD patients. PMID- 26374834 TI - Success of Urgent-Start Peritoneal Dialysis in a Large Canadian Renal Program. AB - ? BACKGROUND: Many patients start renal replacement therapy urgently on in-center hemodialysis via a central venous catheter, which is considered suboptimal. An alternative approach to manage these patients is to start them on peritoneal dialysis (PD). In this report, we describe the first reported Canadian experience with an urgent-start PD program. Additionally we reviewed the literature in this area. ? METHODS: In this prospective observational study, we report on our experience in a single academic center. This program started in July 2010. We included patients who initiated PD urgently, that is within 2 weeks of catheter insertion. We followed all incident PD patients until October 2013 for mechanical and infectious complications. Peritoneal dialysis catheters were inserted either percutaneously or laparoscopically and dialysis was initiated in either an inpatient or outpatient setting. ? RESULTS: Thirty patients were started on urgent PD during our study period. Follow-up ranged from 28 to 1,050 days. Twenty insertions (66.7%) were done percutaneously and 10 (33.3%) were laparoscopic. Dialysis was initiated within 2 weeks (range: 0-13 days, median = 6 days). Twenty four patients (80%) started PD in an outpatient setting and 6 patients (20%) required immediate inpatient PD start. Three patients (10%) developed a minor peri-catheter leak during the first week of training that was managed conservatively. There were no episodes of peritonitis or exit-site/tunnel infection during the first 4 weeks post-insertion. Four patients (13.3%) from the percutaneous insertion group and 2 patients (6.7%) from laparoscopic insertions developed catheter dysfunction due to migration, which was managed by repositioning, without need for catheter replacement or modality switch. ? CONCLUSIONS: Our results are consistent with other studies in this area and demonstrate that urgent-start PD is an acceptable and safe alternative to hemodialysis in patients who need to start dialysis urgently without established dialysis access. PMID- 26374835 TI - Evaluating Hyponatremia in Non-Diabetic Uremic Patients on Peritoneal Dialysis. AB - ? BACKGROUND: An approach to hyponatremia in uremic patients on peritoneal dialysis (PD) necessitates the assessment of intracellular fluid volume (ICV) and extracellular volume (ECV). The aim of the study was to evaluate the association of plasma sodium (Na(+)) concentration and body fluid composition and identify the causes of hyponatremia in non-diabetic PD patients. ? METHODS: Sixty non diabetic uremic patients on PD were enrolled. Baseline body fluid composition, biochemistry, hand-grip test, peritoneal membrane characteristics, dialysis adequacy, Na(+) and water balance, and residual renal function (RRF) were measured. These parameters were reevaluated for those who developed hyponatremia, defined as serum Na(+) concentration < 132 mmol/L and a decline in serum Na(+) > 7 mmol/L, during monthly visits for 1 year. Body fluid composition was determined by multi-frequency bioelectrical impedance (BIA). ? RESULTS: There was no significant correlation between serum Na(+) concentrations and any other parameters except a negative correction with overnight ultrafiltration (UF) amount (p = 0.02). The ICV/ECV ratio was positively correlated with serum albumin (p < 0.005) and hand grip strength (p < 0.05). Over 1 year, 9 patients (M:F = 3:6, aged 35 - 77) with 4 different etiologies of hyponatremia were identified. Hyponatremic patients with a body weight (BW) loss had either an increased ICV/ECV ratio associated with primarily a negative Na(+) balance (n = 2) or a reduced ratio of ICV/ECV associated with malnutrition (n = 2). In contrast, hyponatremic patients with a BW gain had either a reduced ICV/ECV ratio associated with a rapid loss of RRF and a higher peritoneal permeability (n = 2) or a normal to increased ICV/ECV ratio associated with high water intake (n = 3). ? CONCLUSION: Besides BW change and ultrafiltration rate, the assessment of ICV/ECV ratio is valuable in identifying the etiologies of hyponatremia in PD and provides a guide for optimal therapy. PMID- 26374836 TI - Exit-Site Dressing and Infection in Peritoneal Dialysis: A Randomized Controlled Pilot Trial. AB - ? OBJECTIVE: Peritoneal dialysis (PD)-related infection is a common cause of catheter loss and the main reason for PD drop-out. Exit-site infection (ESI) is a pathway to developing tunnel infection and peritonitis, hence rigorous exit-site care has always been emphasized in PD therapy. The aim of this study was to evaluate the effect of exit-site dressing vs non-dressing on the rate of PD related infection. ? METHODS: A prospective randomized controlled study was conducted in prevalent PD patients at the Hospital Tuanku Jaafar Seremban, Negeri Sembilan, Malaysia, from April 2011 until April 2013. All patients were required to perform daily washing of the exit site with antibacterial soap during a shower. In the dressing group (n = 54), patients were required to clean their exit site using povidone-iodine after drying, followed by topical mupirocin antibiotic application to the exit site. The exit site was then covered with a sterile gauze dressing and the catheter immobilized with tape. In the non dressing group (n = 54), patients were not required to do any further dressing after drying. They were only required to apply mupirocin cream to the exit site and then left the exit site uncovered. The catheter was immobilized with tape. The primary outcome was ESI. The secondary outcomes were evidence of tunnel infection or peritonitis. ? RESULTS: A total of 97 patients completed the study. There were a total of 12 ESI episodes: 4 episodes in 4 patients in the dressing group vs 8 episodes in 4 patients in the non-dressing group. This corresponds to 1 episode per 241.3 patient-months vs 1 episode per 111.1 patient-months in the dressing and non-dressing groups respectively. Median time to first ESI episode was shorter in the non-dressing than in the dressing group, but not significant (p = 0.25). The incidence of gram-positive ESI in both groups was similar. There were no gram-negative ESI in the non-dressing group compared with 2 in the dressing group. The peritonitis rate was 1 per 37.1 patient-month in the dressing group and 1 per 44.4 patient-months in the non-dressing group. Median time to first peritonitis episode was significantly shorter in the dressing group compared to non-dressing (p = 0.03). There was no impact of dressing disruptions in the occurrence of major PD catheter-related infection. ? CONCLUSION: Use of a non-dressing technique with only prophylactic topical mupirocin cream application is effective in preventing PD-related infection. The non-dressing technique is more cost-effective and convenient for PD patients, with fewer disposables. PMID- 26374837 TI - Peritoneal Dialysis University for Surgeons: A Peritoneal Access Training Program. AB - ? BACKGROUND: A functioning catheter is vital to the success of peritoneal dialysis (PD). Catheter complications related to the insertion procedure remain a major hindrance to PD utilization. Most catheters are placed by surgeons. Suboptimal catheter outcomes appear to be related to inadequate training and experience during surgical residency and the absence of educational opportunities to remedy this deficit once the surgeon is in practice. ? OBJECTIVE: The aim of this report is to describe a 1-day comprehensive surgeon training program in PD access surgery and to convey the results of the first 7 courses. ? METHODS: Needs assessment data served as the foundation for formulating course objectives and content. A disease-based approach to PD was taken to provide both didactic instruction and laboratory exercises. Surgical simulators permitted skills development for each key task in catheter placement. Educational outcomes were measured with pre- and post-tests, course evaluation, and follow-up survey. ? RESULTS: Seven courses were attended by 134 surgeons with an average faculty to participant ratio of 1:4 during hands-on laboratory sessions. Pre- and post testing demonstrated a class-average normalized educational gain of 50%. On a 5 point Likert scale, the course was scored highly on 14 areas of evaluation with average responses ranging from 4.4 to 4.9. A follow-up survey conducted a mean of 28 months after the programs revealed significantly increased utilization of all 10 course-targeted PD access skills. Participants gave mean scores of 4.6 for improved confidence in case management and 4.4 for better catheter outcomes. ? CONCLUSIONS: A comprehensive 1-day peritoneal access training course can produce long-term self-assessed improvement in surgical management and PD catheter outcomes. PMID- 26374838 TI - Exploiting a precise design of universal synthetic modular regulatory elements to unlock the microbial natural products in Streptomyces. AB - There is a great demand for precisely quantitating the expression of genes of interest in synthetic and systems biotechnology as new and fascinating insights into the genetics of streptomycetes have come to light. Here, we developed, for the first time to our knowledge, a quantitative method based on flow cytometry and a superfolder green fluorescent protein (sfGFP) at single-cell resolution in Streptomyces. Single cells of filamentous bacteria were obtained by releasing the protoplasts from the mycelium, and the dead cells could be distinguished from the viable ones by propidium iodide (PI) staining. With this sophisticated quantitative method, some 200 native or synthetic promoters and 200 ribosomal binding sites (RBSs) were characterized in a high-throughput format. Furthermore, an insulator (RiboJ) was recruited to eliminate the interference between promoters and RBSs and improve the modularity of regulatory elements. Seven synthetic promoters with gradient strength were successfully applied in a proof of-principle approach to activate and overproduce the cryptic lycopene in a predictable manner in Streptomyces avermitilis. Our work therefore presents a quantitative strategy and universal synthetic modular regulatory elements, which will facilitate the functional optimization of gene clusters and the drug discovery process in Streptomyces. PMID- 26374839 TI - Crystal structure reveals specific recognition of a G-quadruplex RNA by a beta turn in the RGG motif of FMRP. AB - Fragile X Mental Retardation Protein (FMRP) is a regulatory RNA binding protein that plays a central role in the development of several human disorders including Fragile X Syndrome (FXS) and autism. FMRP uses an arginine-glycine-rich (RGG) motif for specific interactions with guanine (G)-quadruplexes, mRNA elements implicated in the disease-associated regulation of specific mRNAs. Here we report the 2.8-A crystal structure of the complex between the human FMRP RGG peptide bound to the in vitro selected G-rich RNA. In this model system, the RNA adopts an intramolecular K(+)-stabilized G-quadruplex structure composed of three G quartets and a mixed tetrad connected to an RNA duplex. The RGG peptide specifically binds to the duplex-quadruplex junction, the mixed tetrad, and the duplex region of the RNA through shape complementarity, cation-pi interactions, and multiple hydrogen bonds. Many of these interactions critically depend on a type I beta-turn, a secondary structure element whose formation was not previously recognized in the RGG motif of FMRP. RNA mutagenesis and footprinting experiments indicate that interactions of the peptide with the duplex-quadruplex junction and the duplex of RNA are equally important for affinity and specificity of the RGG-RNA complex formation. These results suggest that specific binding of cellular RNAs by FMRP may involve hydrogen bonding with RNA duplexes and that RNA duplex recognition can be a characteristic RNA binding feature for RGG motifs in other proteins. PMID- 26374840 TI - Endothelial microRNA-150 is an intrinsic suppressor of pathologic ocular neovascularization. AB - Pathologic ocular neovascularization commonly causes blindness. It is critical to identify the factors altered in pathologically proliferating versus normally quiescent vessels to develop effective targeted therapeutics. MicroRNAs regulate both physiological and pathological angiogenesis through modulating expression of gene targets at the posttranscriptional level. However, it is not completely understood if specific microRNAs are altered in pathologic ocular blood vessels, influencing vascular eye diseases. Here we investigated the potential role of a specific microRNA, miR-150, in regulating ocular neovascularization. We found that miR-150 was highly expressed in normal quiescent retinal blood vessels and significantly suppressed in pathologic neovessels in a mouse model of oxygen induced proliferative retinopathy. MiR-150 substantially decreased endothelial cell function including cell proliferation, migration, and tubular formation and specifically suppressed the expression of multiple angiogenic regulators, CXCR4, DLL4, and FZD4, in endothelial cells. Intravitreal injection of miR-150 mimic significantly decreased pathologic retinal neovascularization in vivo in both wild-type and miR-150 knockout mice. Loss of miR-150 significantly promoted angiogenesis in aortic rings and choroidal explants ex vivo and laser-induced choroidal neovascularization in vivo. In conclusion, miR-150 is specifically enriched in quiescent normal vessels and functions as an endothelium-specific endogenous inhibitor of pathologic ocular neovascularization. PMID- 26374842 TI - Laser-based three-dimensional multiscale micropatterning of biocompatible hydrogels for customized tissue engineering scaffolds. AB - Light-induced material phase transitions enable the formation of shapes and patterns from the nano- to the macroscale. From lithographic techniques that enable high-density silicon circuit integration, to laser cutting and welding, light-matter interactions are pervasive in everyday materials fabrication and transformation. These noncontact patterning techniques are ideally suited to reshape soft materials of biological relevance. We present here the use of relatively low-energy (< 2 nJ) ultrafast laser pulses to generate 2D and 3D multiscale patterns in soft silk protein hydrogels without exogenous or chemical cross-linkers. We find that high-resolution features can be generated within bulk hydrogels through nearly 1 cm of material, which is 1.5 orders of magnitude deeper than other biocompatible materials. Examples illustrating the materials, results, and the performance of the machined geometries in vitro and in vivo are presented to demonstrate the versatility of the approach. PMID- 26374841 TI - The myokine irisin increases cortical bone mass. AB - It is unclear how physical activity stimulates new bone synthesis. We explored whether irisin, a newly discovered myokine released upon physical activity, displays anabolic actions on the skeleton. Young male mice were injected with vehicle or recombinant irisin (r-irisin) at a low cumulative weekly dose of 100 ug kg(-1). We observed significant increases in cortical bone mass and strength, notably in cortical tissue mineral density, periosteal circumference, polar moment of inertia, and bending strength. This anabolic action was mediated primarily through the stimulation of bone formation, but with parallel notable reductions in osteoclast numbers. The trabecular compartment of the same bones was spared, as were vertebrae from the same mice. Higher irisin doses (3,500 ug kg(-1) per week) cause browning of adipose tissue; this was not seen with low dose r-irisin. Expectedly, low-dose r-irisin modulated the skeletal genes, Opn and Sost, but not Ucp1 or Ppargamma expression in white adipose tissue. In bone marrow stromal cell cultures, r-irisin rapidly phosphorylated Erk, and up regulated Atf4, Runx2, Osx, Lrp5, beta-catenin, Alp, and Col1a1; this is consistent with a direct receptor-mediated action to stimulate osteogenesis. We also noted that, although the irisin precursor Fndc5 was expressed abundantly in skeletal muscle, other sites, such as bone and brain, also expressed Fndc5, albeit at low levels. Furthermore, muscle fibers from r-irisin-injected mice displayed enhanced Fndc5 positivity, and irisin induced Fdnc5 mRNA expression in cultured myoblasts. Our data therefore highlight a previously unknown action of the myokine irisin, which may be the molecular entity responsible for muscle-bone connectivity. PMID- 26374843 TI - Impact of prolonged leucine supplementation on protein synthesis and lean growth in neonatal pigs. AB - Most low-birth weight infants experience extrauterine growth failure due to reduced nutrient intake as a result of feeding intolerance. The objective of this study was to determine whether prolonged enteral leucine supplementation improves lean growth in neonatal pigs fed a restricted protein diet. Neonatal pigs (n = 14 16/diet, 5 days old, 1.8 +/- 0.3 kg) were fed by gastric catheter a whey-based milk replacement diet with either a high protein (HP) or restricted protein (RP) content or RP supplemented with leucine to the same level as in the HP diet (RPL). Pigs were fed 40 ml.kg body wt(-1).meal(-1) every 4 h for 21 days. Feeding the HP diet resulted in greater total body weight and lean body mass compared with RP-fed pigs (P < 0.05). Masses of the longissimus dorsi muscle, heart, and kidneys were greater in the HP- than RP-fed pigs (P < 0.05). Body weight, lean body mass, and masses of the longissimus dorsi, heart, and kidneys in pigs fed the RPL diet were intermediate to RP- and HP-fed pigs. Protein synthesis and mTOR signaling were increased in all muscles with feeding (P < 0.05); leucine supplementation increased mTOR signaling and protein synthesis rate in the longissimus dorsi (P < 0.05). There was no effect of diet on indices of protein degradation signaling in any tissue (P > 0.05). Thus, when protein intake is chronically restricted, the capacity for leucine supplementation to enhance muscle protein accretion in neonatal pigs that are meal-fed milk protein-based diets is limited. PMID- 26374844 TI - Cyclophilin D, a target for counteracting skeletal muscle dysfunction in mitochondrial myopathy. AB - Muscle weakness and exercise intolerance are hallmark symptoms in mitochondrial disorders. Little is known about the mechanisms leading to impaired skeletal muscle function and ultimately muscle weakness in these patients. In a mouse model of lethal mitochondrial myopathy, the muscle-specific Tfam knock-out (KO) mouse, we previously demonstrated an excessive mitochondrial Ca(2+) uptake in isolated muscle fibers that could be inhibited by the cyclophilin D (CypD) inhibitor, cyclosporine A (CsA). Here we show that the Tfam KO mice have increased CypD levels, and we demonstrate that this increase is a common feature in patients with mitochondrial myopathy. We tested the effect of CsA treatment on Tfam KO mice during the transition from a mild to terminal myopathy. CsA treatment counteracted the development of muscle weakness and improved muscle fiber Ca(2+) handling. Importantly, CsA treatment prolonged the lifespan of these muscle-specific Tfam KO mice. These results demonstrate that CsA treatment is an efficient therapeutic strategy to slow the development of severe mitochondrial myopathy. PMID- 26374846 TI - The twenty-four KDa C-terminal tau fragment increases with aging in tauopathy mice: implications of prion-like properties. AB - The truncated tau protein is a component of the neurofibrillary tangles found in the brains with tauopathies. However, the molecular mechanisms by which the truncated tau fragment causes neurodegeneration remain unknown. Tau pathology was recently suggested to spread through intercellular propagation, and required the formation of 'prion-like' species. We herein identified a new fragment of the tau protein that consisted of four binding domains and a C-terminal tail (Tau-CTF24), but lacked the N-terminal projection domain, and found that it increased with aging in tauopathy model mice (Tg601). Tau-CTF24-like fragments were also present in human brains with tauopathies. A mass spectroscopic analysis revealed that Tau CTF24 was cleaved behind R242. The digestion of full-length tau (Tau-FL) by calpain produced Tau-CTF24 in vitro and calpain activity increased in old Tg601. Recombinant Tau-CTF24 accelerated heparin-induced aggregation and lost the ability to promote microtubule assembly. When insoluble tau from diseased brains or aggregated recombinant tau was introduced as seeds into SH-SY5Y cells, a larger amount of insoluble tau was formed in cells overexpressing Tau-CTF24 than in those overexpressing Tau-FL. Furthermore, lysates containing the Tau-CTF24 inclusion propagated to naive tau-expressing cells more efficiently than those containing the Tau-FL inclusion. Immunoblot and confocal microscopic analyses revealed that aggregated Tau-CTF24 bound to cells more rapidly and abundantly than aggregated Tau-FL. Our results suggest that Tau-CTF24 contributes to neurodegeneration by enhancing prion-like propagation as well as deteriorating the mechanisms involved in microtubule function. PMID- 26374845 TI - A novel porcine model of ataxia telangiectasia reproduces neurological features and motor deficits of human disease. AB - Ataxia telangiectasia (AT) is a progressive multisystem disorder caused by mutations in the AT-mutated (ATM) gene. AT is a neurodegenerative disease primarily characterized by cerebellar degeneration in children leading to motor impairment. The disease progresses with other clinical manifestations including oculocutaneous telangiectasia, immune disorders, increased susceptibly to cancer and respiratory infections. Although genetic investigations and physiological models have established the linkage of ATM with AT onset, the mechanisms linking ATM to neurodegeneration remain undetermined, hindering therapeutic development. Several murine models of AT have been successfully generated showing some of the clinical manifestations of the disease, however they do not fully recapitulate the hallmark neurological phenotype, thus highlighting the need for a more suitable animal model. We engineered a novel porcine model of AT to better phenocopy the disease and bridge the gap between human and current animal models. The initial characterization of AT pigs revealed early cerebellar lesions including loss of Purkinje cells (PCs) and altered cytoarchitecture suggesting a developmental etiology for AT and could advocate for early therapies for AT patients. In addition, similar to patients, AT pigs show growth retardation and develop motor deficit phenotypes. By using the porcine system to model human AT, we established the first animal model showing PC loss and motor features of the human disease. The novel AT pig provides new opportunities to unmask functions and roles of ATM in AT disease and in physiological conditions. PMID- 26374847 TI - Genetic dissection of the Down syndrome critical region. AB - Down syndrome (DS), caused by trisomy 21, is the most common chromosomal disorder associated with developmental cognitive deficits. Despite intensive efforts, the genetic mechanisms underlying developmental cognitive deficits remain poorly understood, and no treatment has been proven effective. The previous mouse-based experiments suggest that the so-called Down syndrome critical region of human chromosome 21 is an important region for this phenotype, which is demarcated by Setd4/Cbr1 and Fam3b/Mx2. We first confirmed the importance of the Cbr1-Fam3b region using compound mutant mice, which carry a duplication spanning the entire human chromosome 21 orthologous region on mouse chromosome 16 [Dp(16)1Yey] and Ms1Rhr. By dividing the Setd4-Mx2 region into complementary Setd4-Kcnj6 and Kcnj15-Mx2 intervals, we started an unbiased dissection through generating and analyzing Dp(16)1Yey/Df(16Setd4-Kcnj6)Yey and Dp(16)1Yey/Df(16Kcnj15-Mx2)Yey mice. Surprisingly, the Dp(16)1Yey-associated cognitive phenotypes were not rescued by either deletion in the compound mutants, suggesting the possible presence of at least one causative gene in each of the two regions. The partial rescue by a Dyrk1a mutation in a compound mutant carrying Dp(16)1Yey and the Dyrk1a mutation confirmed the causative role of Dyrk1a, whereas the absence of a similar rescue by Df(16Dyrk1a-Kcnj6)Yey in Dp(16)1Yey/Df(16Dyrk1a-Kcnj6)Yey mice demonstrated the importance of Kcnj6. Our results revealed the high levels of complexities of gene actions and interactions associated with the Setd4/Cbr1 Fam3b/Mx2 region as well as their relationship with developmental cognitive deficits in DS. PMID- 26374848 TI - Phenotypic, genetic and environmental parameters for traits related to femur bone integrity and body weight at 42 days of age in a broiler population. AB - Intense selection among broilers, especially for performance and carcass traits, currently favors locomotion problems and bone resistance. Conducting studies relating to development and growth of bone tissue in broilers is necessary to minimize losses. Thus, genetic parameters were estimated for a broiler population's phenotypic traits such as BW at 42 d of age (BW42), chilled femur weight (CFW) and its yield (CFY), and femur measurements: calcium, DM, magnesium, phosphorus, and zinc content; breaking strength; rigidity; length; and thickness. Variance components were estimated through multitrait analyses using the restricted maximum likelihood method. The model included a fixed group effect (sex and hatch) and additive and residual genetic random effects. The heritability estimates we obtained ranged from 0.10 +/- 0.05 to 0.50 +/- 0.08 for chilled femur yield and BW42, respectively, and indicated that the traits can respond to the selection process, except for CFY, which presented low-magnitude heritability coefficients. Genetic correlation estimates between breaking strength, rigidity, and traits related to mineral content indicated that selection that aims to improve the breaking strength resistance of the femur is highly correlated with mineral content. Given the genetic correlation estimates between BW42 and minerals, it is suggested that in this population, selection for BW42 can be performed with greater intensity without affecting femoral integrity. PMID- 26374850 TI - Cause of death and CRT device selection: striving for certitude? PMID- 26374849 TI - Influence of ejection fraction on outcomes and efficacy of spironolactone in patients with heart failure with preserved ejection fraction. AB - AIMS: While mineralocorticoid receptor antagonists (MRAs) have been shown to benefit patients with reduced left ventricular ejection fraction (LVEF), spironolactone did not reduce the primary endpoint of cardiovascular death, heart failure hospitalization, or aborted cardiac arrest in patients with heart failure with preserved ejection fraction (HFpEF) in the TOPCAT trial, which enrolled patients with LVEF of 45% or greater. We utilized data from TOPCAT to assess the relationship between LVEF as well as outcomes and efficacy of spironolactone. METHODS AND RESULTS: We assessed differences in baseline characteristics and outcomes across LVEF categories in 3444 patients with HFpEF, and determined whether LVEF modified the treatment effect of spironolactone. Ejection fraction ranged from 44 to 85%. Patients with higher ejection fraction were older, more likely to be female, less likely to have a history of myocardial infarction, and more likely to have a history of hypertension and diabetes. The incidence of the primary endpoint and cardiovascular death was highest in patients at the lower end of the ejection fraction spectrum. Ejection fraction modified the spironolactone treatment effect, particularly in the patients enrolled in the Americas, for the primary outcome (P = 0.046) and for heart failure hospitalization (P = 0.039), with stronger estimated benefits of spironolactone at the lower end of the ejection fraction spectrum with respect to the primary endpoint (LVEF <50%: HR 0.72, 95% CI 0.50, 1.05; LVEF >=60%: HR 0.97, 95% CI 0.76, 1.23) and heart failure hospitalization (LVEF <50%: HR 0.76, 95% CI 0.46, 1.27; LVEF >=60%: HR 0.98, 95% CI 0.74, 1.30). CONCLUSION: In patients with HFpEF enrolled in TOPCAT, patient characteristics and outcomes varied substantially by LVEF. The potential efficacy of spironolactone was greatest at the lower end of the LVEF spectrum. CLINICALTRIALSGOV NUMBER: NCT00094302. PMID- 26374851 TI - Incomplete surgical exclusion of the left atrial appendage. PMID- 26374854 TI - A local VE-cadherin and Trio-based signaling complex stabilizes endothelial junctions through Rac1. PMID- 26374852 TI - Comparison of right ventricular septal pacing and right ventricular apical pacing in patients receiving cardiac resynchronization therapy defibrillators: the SEPTAL CRT Study. AB - AIMS: Cardiac resynchronization therapy (CRT) is a recommended treatment of heart failure (HF) patients with depressed left ventricular ejection fraction and wide QRS. The optimal right ventricular (RV) lead position being a matter of debate, we sought to examine whether RV septal (RVS) pacing was not inferior to RV apical (RVA) pacing on left ventricular reverse remodelling in patients receiving a CRT defibrillator. METHODS AND RESULTS: Patients (n = 263, age = 63.4 +/- 9.5 years) were randomly assigned in a 1:1 ratio to RVS (n = 131) vs. RVA (n = 132) pacing. Left ventricular end-systolic volume (LVESV) reduction between baseline and 6 months was not different between the two groups (-25.3 +/- 39.4 mL in RVS group vs. -29.3 +/- 44.5 mL in RVA group, P = 0.79). Right ventricular septal pacing was not non-inferior (primary endpoint) to RVA pacing with regard to LVESV reduction (average difference = -4.06 mL; P = 0.006 with a -20 mL non-inferiority margin). The percentage of 'echo-responders' defined by LVESV reduction >15% between baseline and 6 months was similar in both groups (50%) with no difference in the time to first HF hospitalization or death (P = 0.532). Procedural or device-related serious adverse events occurred in 68 patients (RVS = 37) with no difference between the two groups (P = 0.401). CONCLUSION: This study demonstrates that septal RV pacing in CRT is non-inferior to apical RV pacing for LV reverse remodelling at 6 months with no difference in the clinical outcome. No recommendation for optimal RV lead position can hence be drawn from this study. CLINICALTRIALS GOV NUMBER: NCT 00833352. PMID- 26374855 TI - Oestrogen receptors interact with the alpha-catalytic subunit of AMP-activated protein kinase. AB - Normal and pathological stressors engage the AMP-activated protein kinase (AMPK) signalling axis to protect the cell from energetic pressures. Sex steroid hormones also play a critical role in energy metabolism and significantly modify pathological progression of cardiac disease, diabetes/obesity and cancer. AMPK is targeted by 17beta-oestradiol (E2), the main circulating oestrogen, but the mechanism by which E2 activates AMPK is currently unknown. Using an oestrogen receptor alpha/beta (ERalpha/beta) positive (T47D) breast cancer cell line, we validated E2-dependent activation of AMPK that was mediated through ERalpha (not ERbeta) by using three experimental strategies. A series of co immunoprecipitation experiments showed that both ERs associated with AMPK in cancer and striated (skeletal and cardiac) muscle cells. We further demonstrated direct binding of ERs to the alpha-catalytic subunit of AMPK within the betagamma subunit-binding domain. Finally, both ERs interacted with the upstream liver kinase B 1 (LKB1) kinase complex, which is required for E2-dependent activation of AMPK. We conclude that E2 activates AMPK through ERalpha by direct interaction with the betagamma-binding domain of AMPKalpha. PMID- 26374856 TI - Subcellular trafficking of guanylyl cyclase/natriuretic peptide receptor-A with concurrent generation of intracellular cGMP. AB - Atrial natriuretic peptide (ANP) activates guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA), which lowers blood pressure and blood volume. The objective of the present study was to visualize internalization and trafficking of enhanced GFP (eGFP)-tagged NPRA (eGFP-NPRA) in human embryonic kidney-293 (HEK 293) cells, using immunofluorescence (IF) and co-immunoprecipitation (co-IP) of eGFP-NPRA. Treatment of cells with ANP initiated rapid internalization and co localization of the receptor with early endosome antigen-1 (EEA-1), which was highest at 5 min and gradually decreased within 30 min. Similarly, co localization of the receptor was observed with lysosome-associated membrane protein-1 (LAMP-1); however, after treatment with lysosomotropic agents, intracellular accumulation of the receptor gradually increased within 30 min. Co IP assays confirmed that the localization of internalized receptors occurred with subcellular organelles during the endocytosis of NPRA. Rab 11, which was used as a recycling endosome (Re) marker, indicated that ~20% of receptors recycled back to the plasma membrane. ANP-treated cells showed a marked increase in the IF of cGMP, whereas receptor was still trafficking into the intracellular compartments. Thus, after ligand binding, NPRA is rapidly internalized and trafficked from the cell surface into endosomes, Res and lysosomes, with concurrent generation of intracellular cGMP. PMID- 26374857 TI - Cyclic nucleotide phosphodiesterase 1 and vascular aging. AB - VSMCs (vascular smooth muscle cells) play critical roles in arterial remodelling with aging, hypertension and atherosclerosis. VSMCs exist in diverse phenotypes and exhibit phenotypic plasticity, e.g. changing from a quiescent/contractile phenotype to an active myofibroblast-like, often called 'synthetic', phenotype. Synthetic VSMCs are able to proliferate, migrate and secrete ECM (extracellular matrix) proteinases and ECM proteins. In addition, they produce pro-inflammatory molecules, providing an inflammatory microenvironment for leucocyte penetration, accumulation and activation. The aging VSMCs have also shown changes in cellular phenotype, responsiveness to contracting and relaxing mediators, replicating potential, matrix synthesis, inflammatory mediators and intracellular signalling. VSMC dysfunction plays a key role in age-associated vascular remodelling. Cyclic nucleotide PDEs (phosphodiesterases), by catalysing cyclic nucleotide hydrolysis, play a critical role in regulating the amplitude, duration and compartmentalization of cyclic nucleotide signalling. Abnormal alterations of PDEs and subsequent changes in cyclic nucleotide homoeostasis have been implicated in a number of different diseases. In the study published in the latest issue of Clinical Science, Bautista Nino and colleagues have shown that, in cultured senescent human VSMCs, PDE1A and PDE1C mRNA levels are significantly up-regulated and inhibition of PDE1 activity with vinpocetine reduced cellular senescent makers in senescent VSMCs. Moreover, in the premature aging mice with genomic instability (Ercc1(d/-)), impaired aortic ring relaxation in response to SNP (sodium nitroprusside), an NO (nitric oxide) donor, was also largely improved by vinpocetine. More interestingly, using data from human GWAS (genome-wide association studies), it has been found that PDE1A single nucleotide polymorphisms is significantly associated with diastolic blood pressure and carotid intima-media thickening, two hallmarks of human vascular dysfunction in aging. These findings establish a strong relationship between PDE1 expression regulation and vascular abnormalities in aging. PMID- 26374858 TI - Increased ubiquitination and reduced plasma membrane trafficking of placental amino acid transporter SNAT-2 in human IUGR. AB - Placental amino acid transport is decreased in intrauterine growth restriction (IUGR); however, the underlying mechanisms remain largely unknown. We have shown that mechanistic target of rapamycin (mTOR) signalling regulates system A amino acid transport by modulating the ubiquitination and plasma membrane trafficking of sodium-coupled neutral amino acid transporter 2 (SNAT-2) in cultured primary human trophoblast cells. We hypothesize that IUGR is associated with (1) inhibition of placental mTORC1 and mTORC2 signalling pathways, (2) increased amino acid transporter ubiquitination in placental homogenates and (3) decreased protein expression of SNAT-2 in the syncytiotrophoblast microvillous plasma membrane (MVM). To test this hypothesis, we collected placental tissue and isolated MVM from women with pregnancies complicated by IUGR (n=25) and gestational age-matched women with appropriately grown control infants (n=19, birth weights between the twenty-fifth to seventy-fifth percentiles). The activity of mTORC1 and mTORC2 was decreased whereas the protein expression of the ubiquitin ligase NEDD4-2 (neural precursor cell expressed developmentally down regulated protein 4-2; +72%, P<0.0001) and the ubiquitination of SNAT-2 (+180%, P<0.05) were increased in homogenates of IUGR placentas. Furthermore, IUGR was associated with decreased system A amino acid transport activity (-72%, P<0.0001) and SNAT-1 (-42%, P<0.05) and SNAT-2 (-31%, P<0.05) protein expression in MVM. In summary, these findings are consistent with the possibility that decreased placental mTOR activity causes down-regulation of placental system A activity by shifting SNAT-2 trafficking towards proteasomal degradation, thereby contributing to decreased fetal amino acid availability and restricted fetal growth in IUGR. PMID- 26374859 TI - Comparing Breast Cancer Outcomes Between Medicaid and the Ohio Breast and Cervical Cancer Early Detection Program. AB - PURPOSE: To compare outcomes between women enrolling in Medicaid after being diagnosed with breast cancer and those referred to Medicaid through the Ohio Breast and Cervical Cancer Early Detection Program (BCCEDP). METHODS: Using linked data from the 2002 to 2008 Ohio Cancer Incidence Surveillance System, Medicaid, the BCCEDP database, and Ohio death certificates (through 2010), we identified women 40 to 64 years of age diagnosed with incident invasive breast cancer during the study years and enrolled in Medicaid 3 months before or after cancer diagnosis. We compared the following outcomes across BCCEDP one-time and repeat participants and nonparticipants: (1) cancer stage at diagnosis, (2) treatment delays, (3) receipt of standard treatment, and (4) survival. We conducted multivariable logistic regression and survival analysis to examine the association between BCCEDP participation and the outcomes of interest, controlling for potential confounders. RESULTS: We identified 427 and 654 BCCEDP participants and nonparticipants, respectively; 28.5% of BCCEDP women were repeat participants. Compared with nonparticipants, BCCEDP one-time and repeat participants were significantly less likely to be diagnosed with advanced-stage cancer (one-time: adjusted odds ratio [AOR], 0.64; 95% CI, 0.49 to 0.85; repeat: AOR, 0.34; 95% CI, 0.23 to 0.52), or experience delays in treatment initiation (one-time: adjusted hazard ratio [AHR], 1.29; 95% CI, 1.09 to 1.51; repeat: AHR, 1.38; 95% CI, 1.11 to 1.72). In addition, although we observed no difference in receipt of standard cancer treatment, BCCEDP participants experienced cancer specific and overall survival benefits. CONCLUSION: Compared with nonparticipants, BCCEDP participants experienced earlier breast cancer stage at diagnosis, shorter time to treatment initiation, and survival benefits. PMID- 26374860 TI - Perspective on the National Comprehensive Cancer Network's Clinical Practice Guidelines for Smoking Cessation. PMID- 26374861 TI - Transition of Care for Inpatient Hematology Patients Receiving Chemotherapy: Development of Hospital Discharge Huddle Process and Effects of Implementation. AB - PURPOSE: To develop a care model to decrease incidence of preventable errors in the complex multidisciplinary care of hematology inpatients at the time of discharge. METHODS: An interactive, multidisciplinary, structured discharge process was developed. Multiple focus groups were held to establish the strengths and gaps. A checklist was created for common follow-up needs. Outcomes measured included: dexamethasone received at discharge, antiemetics prescribed, hospital readmissions, number of patient telephone calls received postdischarge, chemotherapy letters created, pegfilgrastim arranged, and peripherally inserted catheter care arranged. Using a pre-post study design, we compared outcomes of patients after the checklist was implemented in June 2014 (n = 41) with a historical cohort of patients admitted to hematology for chemotherapy 1 year earlier in June 2013 (n = 42). RESULTS: Compared with the historical data, improvement was noted for all checklist items except number of hospital readmissions and number of nursing telephone calls. In June 2014, 100% of patients received pegfilgrastim, compared with 88% in June 2013 (P = .02). Antiemetic prescriptions after chemotherapy improved from 40% (June 2013) to 70% (June 2014; P = .004). Two areas did not show improvement: number of readmissions (12 v 21; P = .26) and number of telephone calls after discharge (nine each for June 2013 and 2014; P = 1.0). CONCLUSION: There was significant decrease in preventable errors demonstrated after implementation of our care model. Developing a systematic approach to hospital discharges can lead to improvements and serve a model for other inpatient wards. PMID- 26374863 TI - ReCAP: Perspectives of Patients, Caregivers, and Medical Staff on Greetings in Oncology Practice: A Prospective Survey. AB - PURPOSE: Encounters between patients and medical staff are the foundation for building the patient-medical staff relationship, which is a keystone of care. We investigated perspectives of patients, caregivers, and medical staff related to greetings in oncology practice. METHODS: A total of 186 patients (median age, 62 years) and 104 caregivers (median age, 54 years) visiting the outpatient clinics at the Davidoff Cancer Institute completed a questionnaire about greeting-related preferences. Similar questionnaires were completed by 93 staff members (physicians, nurses, secretaries, and psychosocial team). RESULTS: Overall, patients preferred to be addressed informally (ie, by their given name) during first and subsequent meetings with their physician (59% and 75% of patients, respectively). However, most physicians (79%) addressed patients more formally (using surname or full name). Overall, 53% of patients wanted the physician to shake their hand. Physicians reported shaking hands with their patients at the beginning (46%) or end (71%) of the first meeting. Most patients (76%) wanted physicians to formally introduce themselves (by their full name) and mention their academic degree (65%). For other oncology professionals, a majority of patients (63%) preferred an informal introduction (by given name only). No major differences were observed between patients' and caregivers' perspectives. CONCLUSION: This survey provides insights that may help oncology professionals in building relationships with their patients. Specifically, our findings suggest that patients with cancer in Israel prefer a casual environment; yet, they prefer that physicians introduce themselves in a more formal manner. PMID- 26374862 TI - Serum Tumor Marker Use in Patients With Advanced Solid Tumors. AB - PURPOSE: There is substantial variability in the frequency of serum tumor marker testing in patients with advanced solid tumors. We performed a retrospective analysis to evaluate the frequency of serum tumor marker use. METHODS: Patients with a diagnosis of advanced cancer with outpatient visits between July 1, 2013, and June 30, 2014, at a single center were included. Tumor and stage were determined by International Classification of Diseases, Ninth Revision codes and confirmed with tumor registry and medical record review. For each patient, we recorded the dates of each of the following tumor markers: a-fetoprotein, CA-125, CA 15-3, CA 19-9, CA 27-29, and carcinoembryonic antigen. We evaluated the number of tests per patient over 12 months and the maximum number of tests per patient per month. RESULTS: We included 928 patients in the analysis. The mean number of any individual test per patient was seven tests, and the maximum number was 35 tests; the mean number of total tests per patient was 12 tests, and the maximum number was 70 tests; 16.3% of patients had more than 12 individual tests per year. In a 1-month span, 34.3% of patients had more than one individual test. CA 19-9 and carcinoembryonic antigen were the most commonly overused tests. CONCLUSION: We found a high rate of serum tumor marker testing use in patients with advanced solid tumors. Given the increasing costs of cancer care, efforts should be made to determine the benefit of serum tumor markers in the follow-up care of patients with advanced solid tumors. PMID- 26374865 TI - Giant pseudoaneurysm compressing right coronary artery postinfective endocarditis. PMID- 26374864 TI - Investigating a Proposed Model of Social Competence in Children With Traumatic Brain Injuries. AB - OBJECTIVE: The goal of the current study was to test a proposed model of social competence for children who have suffered a traumatic brain injury (TBI). We hypothesized that both peer and teacher reports of social behavior would mediate the relation between intraindividual characteristics (e.g., executive function) and peer acceptance. METHODS: Participants were 52 children with TBI (M age = 10.29; M time after injury: 2.46 years). Severity of TBI ranged from complicated mild to severe. Classroom and laboratory measures were used to assess executive function, social behavior, and peer acceptance. RESULTS: Analyses revealed that peer reports of social behavior were a better mediator than teacher reports of the associations between executive function, social behaviors, and peer acceptance. DISCUSSION: The results underscore the importance of including peer reports of social behavior when developing interventions designed to improve the social, emotional, and behavioral outcomes of children with TBI. PMID- 26374866 TI - Pulmonary middle lobectomy for non-small-cell lung cancer: effectiveness and prognostic implications. AB - OBJECTIVES: The therapeutic value of pulmonary middle lobectomy (PML) has been questioned. PML is currently regarded as a standard form of lobectomy, even so it shares some surgical features with segmentectomies (SEG) more than with lobectomies. The present study's aim was to assess the therapeutic value of PML with respect to other lobectomies (LOBs) and SEGs. METHODS: A total of 902 consecutive patients who underwent lobectomy or SEG with mediastinal lymph node dissection for Stage I-IIIa non-small-cell lung cancer were analysed. Patients with pT4 tumours and/or pathologically incomplete resection were excluded. RESULTS: PML was performed in 50 patients, SEG in 44 and LOBs were performed in 808. The three study groups were homogeneous, except for gender, pT and grade: females, pT1 and G1 tumours were more frequent in the PML and SEG groups. The lymph node dissection yield was poorer in PML (P < 0.007) and SEG (P < 0.001) groups when compared with LOB group. Five-year overall survival (OS) was 45.3% for PML, 54.0% for SEG and 60.2% for LOB (P = 0.793). When limiting the analysis to G2-3 right-sided tumours, 5-year survival was lower in the PML group than in the LOB group: 41.3 vs 59.0% (P = 0.057). Similar results were found when analysing pT2-3 right-sided tumours: 27.3 vs 57.3% (P = 0.049). Multivariable analysis showed four independent prognostic factors: age (P = 0.001), pathological stage (P < 0.001), gender (P = 0.005) and the type of surgical resection (P = 0.029). PML (hazard ratio, HR = 1.63) and SEG (HR = 1.64) were detrimental in comparison with LOB. After adjusting for baseline differences between groups (propensity score), a trend towards a worse OS in PML group when compared with LOB group was observed (HR = 1.38, P = 0.150). CONCLUSIONS: Both the lymphadenectomy yield and prognosis make PML more similar to SEG than lobectomy, especially for pT2-3 or G2-3 tumours. PMID- 26374867 TI - Surgical management of congenital tracheal stenosis associated with tracheal bronchus and congenital heart disease. AB - OBJECTIVES: Congenital tracheal stenosis (CTS) is variable in patients with tracheal bronchus and congenital heart disease (CHD). Tracheoplasty remains a high-risk surgical treatment. METHODS: From January 2007 to December 2014, 24 CTS patients (10 males and 14 females; age 20.6 +/- 13.6 months) with tracheal bronchus and CHD underwent one-stage surgical correction. Clinical features of all patients included dyspnoea, or recurrent pulmonary infections. There was long segment CTS in 13 cases (54%), and 4 cases were associated with a bridging bronchus. Less than 50% of normal tracheal size was identified in 21 cases. Complete tracheal or bronchial rings were identified in all cases. Operative techniques included: tracheal end-to-end anastomosis in 11 cases and slide tracheoplasty in 13 cases, which included 11 cases of right upper lobe bronchus (RULB) opposite side-slide tracheoplasty. RESULTS: There were 2 operative deaths, due to postoperative tracheomalacia or residual main bronchial stenosis. The duration of postoperative hospital stay was 7-59 days, with an average of 19 days. Follow-up was completed in 19 cases. The follow-up duration was from 1 month to 7 years. Tracheal granulation occurred in 1 case. Clinical symptoms were significantly improved in the remaining patients. CONCLUSIONS: Tracheal bronchi have special anatomical features. The techniques of tracheal end-to-end anastomosis or side-slide tracheoplasty can be used to correct tracheal stenosis with satisfactory outcomes. PMID- 26374868 TI - Transition from a multiport technique to a single-port technique for lung cancer surgery: is lymph node dissection inferior using the single-port technique??. AB - OBJECTIVES: The feasibility and radicalism of lymph node dissection for lung cancer surgery by a single-port technique has frequently been challenged. We performed a retrospective cohort study to investigate this issue. METHODS: Two chest surgeons initiated multiple-port thoracoscopic surgery in a 180-bed cancer centre in 2005 and shifted to a single-port technique gradually after 2010. Data, including demographic and clinical information, from 389 patients receiving multiport thoracoscopic lobectomy or segmentectomy and 149 consecutive patients undergoing either single-port lobectomy or segmentectomy for primary non-small cell lung cancer were retrieved and entered for statistical analysis by multivariable linear regression models and Box-Cox transformed multivariable analysis. RESULTS: The mean number of total dissected lymph nodes in the lobectomy group was 28.5 +/- 11.7 for the single-port group versus 25.2 +/- 11.3 for the multiport group; the mean number of total dissected lymph nodes in the segmentectomy group was 19.5 +/- 10.8 for the single-port group versus 17.9 +/- 10.3 for the multiport group. In linear multivariable and after Box-Cox transformed multivariable analyses, the single-port approach was still associated with a higher total number of dissected lymph nodes. CONCLUSIONS: The total number of dissected lymph nodes for primary lung cancer surgery by single-port video-assisted thoracoscopic surgery (VATS) was higher than by multiport VATS in univariable, multivariable linear regression and Box-Cox transformed multivariable analyses. This study confirmed that highly effective lymph node dissection could be achieved through single-port VATS in our setting. PMID- 26374869 TI - Factors associated with preserved pulmonary function in non-small-cell lung cancer patients after video-assisted thoracic surgery. AB - OBJECTIVES: Some non-small-cell lung cancer patients have preserved pulmonary function after surgery. Compared with open thoracotomy, video-assisted thoracic surgery (VATS) is widely performed and preserves pulmonary function. Patients with non-small-cell lung cancer have an extremely poor prognosis without surgery. Clinicians should therefore decide which patients can safely tolerate lung resection. This study aimed to identify factors associated with preserving pulmonary function after VATS in non-small-cell lung cancer patients. METHODS: Three hundred and fifty-one patients with non-small-cell lung cancer underwent VATS and preoperative and 12-month postoperative pulmonary function tests. Patients with and patients without preserved forced expiratory volume in 1 s (FEV1) and diffusing capacity of carbon monoxide were compared. RESULTS: The FEV1 was preserved after VATS in 142 (40.5%) patients. In multivariable analysis, this group was significantly associated with VATS sublobar resection (P < 0.001) and resection at the right upper lobe or right middle lobe (vs right lower lobe, P = 0.048; vs left upper lobe, P = 0.003; vs left lower lobe, P = 0.015). Diffusing capacity of carbon monoxide was preserved in 129 (36.8%) patients. Multivariable analysis showed that VATS sublobar resection (P < .001), lower baseline diffusing capacity of carbon monoxide (P < 0.001) and right upper lobe or right middle lobe resection (vs right lower lobe, P = 0.0014; vs left upper lobe, P = 0.029, vs left lower lobe, P = 0.014) were significantly associated with preserved diffusing capacity of carbon monoxide. CONCLUSIONS: For preserving pulmonary function after non-small-cell lung cancer surgery, VATS sublobar resection was superior to VATS lobectomy, and surgery on the right upper lobe or right middle lobe was superior to that at other sites. PMID- 26374870 TI - Systematic reviews and meta-analyses: black boxes of medical literature? PMID- 26374871 TI - Risk factors for mortality after pericardiectomy for chronic constrictive pericarditis in a large single-centre cohort. AB - OBJECTIVES: Constrictive pericarditis (CP) is an uncommon disease with multiple causes and unclear clinical outcomes. To date, few publications have clearly defined risk factors of poor outcomes after surgery for CP. We performed a retrospective analysis of almost 100 patients undergoing surgical treatment for CP at a single institution in order to identify risk factors for perioperative and long-term mortality. METHODS: A total of 97 consecutive patients (67.0% male) undergoing surgery for CP at our institution from 1995 to 2012 were included in the study. CP was diagnosed either preoperatively by cardiac catheterization and appropriate imaging or during surgery. Preoperative and intraoperative risk factors for 30-day and late mortality were analysed using stepwise multivariate logistic and Cox regression analyses. Median follow-up was 1.23 +/- 3.96 years (mean 3.08 +/- 3.96 years). RESULTS: The mean patient age was 60.0 +/- 12.5 years and the underlying aetiology was idiopathic (50.5%), prior cardiac surgery (15.5%), prior mediastinal radiation (9.3%), and miscellaneous (24.7%). All patients underwent either radical (55.2%) or partial (44.8%) pericardiectomy. Concomitant procedures were performed in 54 (55.7%) patients. The total procedure time was 197.0 +/- 105.0 min. Cardiopulmonary bypass (CPB) was used in 62 patients with a corresponding CPB time of 124.8 +/- 68.4 min. In those patients who underwent CPB, cardioplegic arrest was performed in 53.2% of patients with a mean cross-clamp time of 74.9 +/- 41.9 min. Overall 30-day, 1-year and 5-year survival rates were 81.4, 66.5 and 51.6%, respectively, without significant differences according to the underlying aetiology. Multivariate analysis revealed patients with reduced left ventricular ejection fraction (LVEF) [P = 0.01, odds ratio (OR) 3.6] and preoperative right ventricular dilatation (P = 0.04, OR 3.5) to be at significant risk of early mortality. Long-term mortality was independently predicted by the presence of coronary artery disease (CAD) [P < 0.001, hazard ratio (HR) 6.44], chronic obstructive pulmonary disease (P = 0.001, HR 4.21) and preoperative renal insufficiency (P = 0.012, HR 1.8). Concomitant tricuspid valve repair (TVR) appeared to provide protective effect on the long term survival (P = 0.07). CONCLUSIONS: Surgery for CP is associated with a significant risk based on the poor preoperative patient status. Whenever justified, partial over radical pericardiectomy should be preferred and TVR should be indicated liberally. Reduced LVEF and right ventricular dilatation were independent predictors for early mortality, whereas CAD, chronic obstructive pulmonary disease and renal insufficiency were risk factors for late mortality. Thus, an optimal timing for surgery on CP remains crucial to avoid secondary morbidity with an even worse natural prognosis. PMID- 26374872 TI - Clinical characteristics and advantages of primary peripheral micro-sized lung adenocarcinoma over small-sized lung adenocarcinoma. AB - OBJECTIVES: Micro-sized lung adenocarcinoma with a tumour of 1.0 cm or less could help identify the patients who would undergo the surgery treatment with limited resection; however, its clinical characteristics and survival rates remain unclear and are to be tested further. METHODS: Histology, lymphatic metastasis, surgical procedure and survival rates of 366 lung adenocarcinoma patients (from January 2007 to December 2013) with a tumour of 2.0 cm or less were analysed retrospectively. Among these patients, 175 had a primary tumour with a diameter of 1.0 cm or less and 191 had a tumour of 1.1-2.0 cm. The survival of 366 patients was evaluated by the restricted mean survival time (RMST) test, and the risk factors were assessed by multivariable analysis. RESULTS: Larger lesion had a significant relation to old age, male sex, preoperatively carcinoembryonic antigen (CEA) positive, invasive adenocarcinoma (IAC) and advanced-stage disease (P < 0.0001, P = 0.001, P = 0.001, P < 0.0001 and P < 0.0001, respectively). Patients with adenocarcinoma in situ (AIS)/minimally invasive adenocarcinoma obtained a better prognosis than those with IAC (5-year overall survival rate: 98.5 vs 84.3%, P = 0.001; disease-related survival rate: 98.5 versus 85.2%, P = 0.001). The 5-year overall survival rates of patients with a tumour less than 1.0 cm in comparison with 1.1-2.0 cm were 100.0 and 88.4% (P < 0.001), whereas the 5 year lung adenocarcinoma-specific survival rates were 100.0 and 89.0% (P < 0.001), respectively. Multivariable analysis for prognosis of lung adenocarcinoma patients with a tumour 2.0 cm or less in diameter revealed that histology, lymphatic metastasis and advanced pathological stage affected the 5-year overall and disease-related survival rates unfavourably (P < 0.0001, 0.002, 0.001; and P < 0.0001, 0.005, 0.001, respectively), whereas tumour size did not have an obvious influence on survival. CONCLUSIONS: Micro-sized lung adenocarcinoma (1.0 cm or less) had specific clinical characteristics and more favourable survival rates. These tumours and a subtype of AIS evaluated by computed tomography images or intraoperative frozen section may be appropriate candidates for a limited resection without mediastinal lymph node dissection. PMID- 26374873 TI - Five-year prospective evaluation of thyroid function in girls with subclinical mild hypothyroidism of different etiology. AB - AIM: To follow-up for 5 years thyroid status evolution in 127 girls with mild (TSH 5-10 mU/l) subclinical hypothyroidism (SH) of different etiologies. PATIENTS: The population was divided into two age-matched groups of 42 and 85 girls with either idiopathic (group A) or Hashimoto's thyroiditis (HT)-related SH (group B). Group B was in turn divided into three subgroups, according to whether SH was either isolated or associated with Turner syndrome (TS) or Down syndrome (DS). RESULTS: At the end of follow-up the rate of girls who became euthyroid was higher in group A (61.9% vs 10.6%), whereas the rates of patients who remained SH (55.3% vs 26.2%), became overtly hypothyroid (30.6% vs 11.9%) or required levothyroxine (l-T4) therapy (63.5% vs 23.8%) were higher in group B. Among the girls of group B, the risk of remaining SH or developing overt hypothyroidism was higher in the subgroups with TS or DS than in those with isolated HT. CONCLUSIONS: Long-term prognosis of mild and idiopathic SH is frequently benign, even though a l-T4 treatment may be needed throughout follow-up in almost a quarter of cases; long-term prognosis is different in the girls with either idiopathic or HT-related SH; and the association with either TS or DS impairs the outcome of HT-related SH. PMID- 26374874 TI - Cardiopulmonary Exercise Testing and Prognosis in Hypertrophic Cardiomyopathy. AB - BACKGROUND: Exercise testing is performed in patients with hypertrophic cardiomyopathy to evaluate blood pressure response, a risk factor for sudden cardiac death. The prognostic role of exercise gas exchange variables is unknown. METHODS AND RESULTS: Between 1998 and 2010, 1898 patients (age 47+/-15 years, range 16-86 years; 67% male) with hypertrophic cardiomyopathy underwent cardiopulmonary exercise testing. A total of 178 (9.4%) patients reached the primary end point of all-cause mortality or heart transplant (death/transplant) during a median follow-up of 5.6 years (interquartile range 2.6-8.9), giving an annual event rate of 1.6% per person year. Peak oxygen consumption (adjusted hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.77-0.88, P<0.001), ventilatory efficiency (adjusted HR 1.10, 95% CI 1.00-1.22, P=0.049), and ventilatory anaerobic threshold (adjusted HR 0.82, 95% CI 0.70-0.96, P=0.016) were predictors of the primary outcome after correction for age, sex, left atrial size, nonsustained ventricular tachycardia, and ejection fraction. The overall adjusted death/transplant estimates for patients in the lowest quartile with peak oxygen consumption <=15.3 mL/kg/min were 14% at 5 years and 31% at 10 years. Peak oxygen consumption (HR 0.81, 95% CI 0.77-0.86, P<0.01) and ventilation to carbon dioxide production (HR 1.10, 95% CI 1.08-1.13, P<0.001) were predictors of death because of heart failure or transplantation but not sudden cardiac death or implantable cardioverter defibrillator shocks. CONCLUSIONS: Cardiopulmonary exercise testing provides prognostic information in patients with hypertrophic cardiomyopathy. Submaximal exercise parameters, such as ventilatory efficiency and anaerobic threshold, measured alone or in combination with peak oxygen consumption, predict death from heart failure. PMID- 26374875 TI - Mitophagy in steatotic hepatocytes of ethanol-treated wild-type and Parkin knockout mice. PMID- 26374876 TI - Mitophagy, mitochondrial spheroids, and mitochondrial-derived vesicles in alcohol induced liver injury. PMID- 26374878 TI - Last Word on Viewpoint: Can elite athletes benefit from dietary nitrate supplementation? PMID- 26374877 TI - Commentaries on Viewpoint: Can elite athletes benefit from dietary nitrate supplementation? PMID- 26374879 TI - Does the aortic annulus undergo conformational change throughout the cardiac cycle? A systematic review. AB - Accurate annular sizing in transcatheter aortic valve implantation (TAVI) planning is essential. It is now widely recognized that the annulus is an oval structure in most patients, but it remains unclear if the annulus undergoes change in size and shape during the cardiac cycle that may impact prosthesis size selection. Our aim was to assess whether the aortic annulus undergoes dynamic conformational change during the cardiac cycle and to evaluate possible implications for prosthesis size selection. We performed a systematic search in PubMed and Embase databases and reviewed all available literature on aortic annulus measurements in at least two cardiac phases. Twenty-nine articles published from 2001 to 2014 were included. In total, 2021 subjects with and without aortic stenosis were evaluated with a mean age ranging from 11 +/- 3.6 to 84.9 +/- 7.2 years. Two- and three-dimensional echocardiography was performed in six studies each, magnetic resonance imaging was used in one and computed tomography in 17 studies. In general, the aortic annulus was more circular in systole and predominantly oval in diastole. Whereas the annular long-axis diameter showed insignificant change throughout the cycle, the short-axis diameter, area, and perimeter were significantly larger in systole compared with diastole. Hence, the aortic annulus does undergo dynamic changes during the cardiac cycle. In patients with large conformational changes, diastolic compared with systolic measurements can result in undersizing TAVI prostheses. Due to the complex annular anatomy and dynamic change, three-dimensional assessment in multiple phases has utmost importance in TAVI planning to improve prosthesis sizing. PMID- 26374881 TI - Reduced contrast media volumes for CT imaging of TAVI candidates. PMID- 26374880 TI - Interstudy heterogeneity of definitions of diastolic dysfunction severely affects reported prevalence. AB - AIMS: The aim of this article is to examine how the European Association of Cardiovascular Imaging (EACVI) and the American Society of Echocardiography (ASE) recommendations on the classification of diastolic dysfunction (DDF) are interpreted in the scientific community and to explore how variations in the DDF definition affect the reported prevalence. METHODS AND RESULTS: A systematic review of studies citing the EACVI/ASE consensus document 'Recommendations for the evaluation of left ventricular diastolic function by echocardiography' was performed. The definition of DDF used in each study was recorded. Subsequently, several possible interpretations of the EACVI/ASE classification scheme were used to obtain DDF prevalence in a community-based sample (n = 714). In the systematic review, 60 studies were included. In 13 studies, no specification of DDF definition was presented, a one-level classification tree was used in 13, a two level classification tree in 18, and in the remaining 16 studies, a DDF definition was presented but no grading of DDF was performed. In 17 studies, the DDF definition relied solely on early diastolic tissue velocity and/or left atrial size. In eight of these studies, a single parameter was used, in two studies the logical operator AND was used to combine two or more parameters, and the remaining seven studies used the logical operator OR. The resulting prevalence of DDF in the community-based sample varied from 12 to 84%, depending on the DDF definition used. CONCLUSION: A substantial heterogeneity of definitions of DDF was evident among the studies reviewed, and the different definitions had a substantial impact on the reported prevalence of DDF. PMID- 26374882 TI - Ultra Performance Liquid Chromatography with Tandem Mass Spectrometry for the Quantitation of Seventeen Sedative Hypnotics in Six Common Toxicological Matrices. AB - An ultra performance liquid chromatography triple quadrupole mass spectrometry (LC-MS-MS) method for the quantification of 14 benzodiazepines and three sedative hypnotics is presented. The fast and inexpensive assay was developed for California's Orange County Crime Lab for use in antemortem (AM) and postmortem casework. The drugs were rapidly cleaned up from AM blood, postmortem blood, urine, liver, brain and stomach contents using DPX((r)) Weak Anion Exchange (DPX WAX) tips fitted on a pneumatic extractor, which can process up to 48 samples at one time. Assay performance was determined for validation based on recommendations by the Scientific Working Group for Forensic Toxicology for linearity, limit of quantitation, limit of detection, bias, precision (within run and between run), dilution integrity, carry-over, selectivity, recovery, ion suppression and extracted sample stability. Linearity was verified using the therapeutic and toxic ranges of all 17 analytes. Final verification of the method was confirmed by four analysts using 20 blind matrix matched samples. All results were within 20% of each other and the expected value. PMID- 26374883 TI - Auxin signal transduction. AB - The plant hormone auxin (indole-3-acetic acid, IAA) controls growth and developmental responses throughout the life of a plant. A combination of molecular, genetic and biochemical approaches has identified several key components involved in auxin signal transduction. Rapid auxin responses in the nucleus include transcriptional activation of auxin-regulated genes and degradation of transcriptional repressor proteins. The nuclear auxin receptor is an integral component of the protein degradation machinery. Although auxin signalling in the nucleus appears to be short and simple, recent studies indicate that there is a high degree of diversity and complexity, largely due to the existence of multigene families for each of the major molecular components. Current studies are attempting to identify interacting partners among these families, and to define the molecular mechanisms involved in the interactions. Future goals are to determine the levels of regulation of the key components of the transcriptional complex, to identify higher-order complexes and to integrate this pathway with other auxin signal transduction pathways, such as the pathway that is activated by auxin binding to a different receptor at the outer surface of the plasma membrane. In this case, auxin binding triggers a signal cascade that affects a number of rapid cytoplasmic responses. Details of this pathway are currently under investigation. PMID- 26374884 TI - Plant cytokinin signalling. AB - Cytokinin is an essential plant hormone that is involved in a wide range of plant growth and developmental processes which are controlled through its signalling pathway. Cytokinins are a class of molecules that are N(6)-substituted adenine derivatives, such as isopentenyl adenine, and trans- and cis-zeatin, which are common in most plants. The ability to perceive and respond to cytokinin occurs through a modified bacterial two-component pathway that functions via a multi step phosphorelay. This cytokinin signalling process is a crucial part of almost all stages of plant life, from embryo patterning to apical meristem regulation, organ development and eventually senescence. The cytokinin signalling pathway involves the co-ordination of three types of proteins: histidine kinase receptors to perceive the signal, histidine phosphotransfer proteins to relay the signal, and response regulators to provide signal output. This pathway contains both positive and negative elements that function in a complex co-ordinated manner to control cytokinin-regulated plant responses. Although much is known about how this cytokinin signal is perceived and initially regulated, there are still many avenues that need to be explored before the role of cytokinin in the control of plant processes is fully understood. PMID- 26374885 TI - Abscisic acid: biosynthesis, inactivation, homoeostasis and signalling. AB - The phytohormone abscisic acid (ABA) plays crucial roles in numerous physiological processes during plant growth and abiotic stress responses. The endogenous ABA level is controlled by complex regulatory mechanisms involving biosynthesis, catabolism, transport and signal transduction pathways. This complex regulatory network may target multiple levels, including transcription, translation and post-translational regulation of genes involved in ABA responses. Most of the genes involved in ABA biosynthesis, catabolism and transport have been characterized. The local ABA concentration is critical for initiating ABA mediated signalling during plant development and in response to environmental changes. In this chapter we discuss the mechanisms that regulate ABA biosynthesis, catabolism, transport and homoeostasis. We also present the findings of recent research on ABA perception by cellular receptors, and ABA signalling in response to cellular and environmental conditions. PMID- 26374886 TI - GA signalling and cross-talk with other signalling pathways. AB - Gibberellins (GAs) are phytohormones that regulate growth and development. DELLA proteins repress GA responses. GA binding to its receptor triggers a series of events that culminate in the destruction of DELLA proteins by the 26S proteasome, which removes the repression of GA signalling. DELLA proteins are transcription co-activators that induce the expression of genes which encode products that inhibit GA responses. In addition to repressing GA responses, DELLA proteins influence the activity of other signalling pathways and serve as a central hub from which other pathways influence GA signalling. In this role, DELLA proteins bind to and inhibit proteins, including transcription factors that act in the signalling pathways of other hormones and light. The binding of these proteins to DELLA proteins also inhibits DELLA activity. GA signalling is subject to homoeostatic regulation through GA-induced repression of GA biosynthesis gene expression, and increased production of the GA receptor and enzymes that catabolize bioactive GAs. This review also discusses the nature of mutant DELLA alleles that are used to produce high-yielding 'Green Revolution' cereal varieties, and highlights important gaps in our knowledge of GA signalling. PMID- 26374887 TI - Mechanisms of ethylene biosynthesis and response in plants. AB - Ethylene is the simplest unsaturated hydrocarbon, yet it has profound effects on plant growth and development, including many agriculturally important phenomena. Analysis of the mechanisms underlying ethylene biosynthesis and signalling have resulted in the elucidation of multistep mechanisms which at first glance appear simple, but in fact represent several levels of control to tightly regulate the level of production and response. Ethylene biosynthesis represents a two-step process that is regulated at both the transcriptional and post-translational levels, thus enabling plants to control the amount of ethylene produced with regard to promotion of responses such as climacteric flower senescence and fruit ripening. Ethylene production subsequently results in activation of the ethylene response, as ethylene accumulation will trigger the ethylene signalling pathway to activate ethylene-dependent transcription for promotion of the response and for resetting the pathway. A more detailed knowledge of the mechanisms underlying biosynthesis and the ethylene response will ultimately enable new approaches to be developed for control of the initiation and progression of ethylene-dependent developmental processes, many of which are of horticultural significance. PMID- 26374888 TI - The molecular circuit of steroid signalling in plants. AB - Steroid hormones are key regulators of growth and physiology in both plants and animals. The plant steroid hormones known as brassinosteroids (BRs) are essential for a wide range of developmental processes throughout the life cycle. In contrast with animal steroid hormones, which act mostly through nuclear receptors, BRs act through a cell-surface receptor kinase. The BR signal transduction pathway from the cell-surface receptor to nuclear gene expression has been elucidated in great molecular detail, and thus serves as a paradigm for receptor kinase signalling in plants. Furthermore, several mechanisms of signal integration have been identified that explain how BRs and other hormonal and environmental signals co-regulate specific developmental outputs in a synergistic or antagonistic manner. PMID- 26374889 TI - Novel players fine-tune plant trade-offs. AB - Jasmonates (JAs) are essential signalling molecules that co-ordinate the plant response to biotic and abiotic challenges, as well as co-ordinating several developmental processes. Huge progress has been made over the last decade in understanding the components and mechanisms that govern JA perception and signalling. The bioactive form of the hormone, (+)-7-iso-jasmonyl-L-isoleucine (JA-Ile), is perceived by the COI1-JAZ co-receptor complex. JASMONATE ZIM DOMAIN (JAZ) proteins also act as direct repressors of transcriptional activators such as MYC2. In the emerging picture of JA-Ile perception and signalling, COI1 operates as an E3 ubiquitin ligase that upon binding of JA-Ile targets JAZ repressors for degradation by the 26S proteasome, thereby derepressing transcription factors such as MYC2, which in turn activate JA-Ile-dependent transcriptional reprogramming. It is noteworthy that MYCs and different spliced variants of the JAZ proteins are involved in a negative regulatory feedback loop, which suggests a model that rapidly turns the transcriptional JA-Ile responses on and off and thereby avoids a detrimental overactivation of the pathway. This chapter highlights the most recent advances in our understanding of JA-Ile signalling, focusing on the latest repertoire of new targets of JAZ proteins to control different sets of JA-Ile-mediated responses, novel mechanisms of negative regulation of JA-Ile signalling, and hormonal cross-talk at the molecular level that ultimately determines plant adaptability and survival. PMID- 26374890 TI - Salicylic acid signalling: new insights and prospects at a quarter-century milestone. AB - The plant hormone salicylic acid (SA) plays an essential role in the regulation of diverse biological processes throughout the entire lifespan of the plant. Twenty-five years ago, SA first emerged as an endogenous signal capable of inducing plant defence responses both at the site of infection and in the systemic tissue of the plant. Since then, SA-mediated signalling pathways have been extensively characterized and dissected using genetic and biochemical approaches. Current research is largely focused on the identification of novel SA downstream signalling genes, in order to understand their precise contributions to the phytohormonal cross-talk and signalling network. This will subsequently help us to identify novel targets that are important for plant health, and contribute to advances in modern agriculture. In this chapter we highlight recent advances in the field of SA biosynthesis and the discovery of candidates for systemic mobile signals. We also discuss the molecular mechanisms underlying SA perception. In addition, we review the novel SA signalling components that expand the scope of SA functions beyond plant immunity to include plant growth and development, endoplasmic reticulum (ER) stress, DNA repair and homologous recombination. Finally, we shed light on the roles of SA in epigenetically controlled transgenerational immune memory that has long-term benefits for plants. PMID- 26374891 TI - Plant peptide hormone signalling. AB - The ligand-receptor-based cell-to-cell communication system is one of the most important molecular bases for the establishment of complex multicellular organisms. Plants have evolved highly complex intercellular communication systems. Historical studies have identified several molecules, designated phytohormones, that function in these processes. Recent advances in molecular biological analyses have identified phytohormone receptors and signalling mediators, and have led to the discovery of numerous peptide-based signalling molecules. Subsequent analyses have revealed the involvement in and contribution of these peptides to multiple aspects of the plant life cycle, including development and environmental responses, similar to the functions of canonical phytohormones. On the basis of this knowledge, the view that these peptide hormones are pivotal regulators in plants is becoming increasingly accepted. Peptide hormones are transcribed from the genome and translated into peptides. However, these peptides generally undergo further post-translational modifications to enable them to exert their function. Peptide hormones are expressed in and secreted from specific cells or tissues. Apoplastic peptides are perceived by specialized receptors that are located at the surface of target cells. Peptide hormone-receptor complexes activate intracellular signalling through downstream molecules, including kinases and transcription factors, which then trigger cellular events. In this chapter we provide a comprehensive summary of the biological functions of peptide hormones, focusing on how they mature and the ways in which they modulate plant functions. PMID- 26374892 TI - Florigens and antiflorigens: a molecular genetic understanding. AB - Florigens, the leaf-derived signals that initiate flowering, have been described as 'mysterious', 'elusive' and the 'Holy Grail' of plant biology. They are synthesized in response to appropriate photoperiods and move through the phloem tissue. It has been proposed that their composition is complex. The evidence that flowering locus T (FT) protein and its paralogue twin sister of FT (TSF) act as florigen, or represent at least part of it, in diverse plant species has attracted considerable attention. In Arabidopsis thaliana, inductive photoperiodic conditions perceived in the leaf lead to stabilization of CONSTANS protein, which induces FT and TSF transcription. When they have been translated in the phloem companion cells, FT and TSF enter the phloem stream and are conveyed to the shoot apical meristem, where they act together with flowering locus D to activate transcription of floral meristem identity genes, resulting in floral initiation. At least part of this model is conserved, with some variations in several species. In addition to florigen(s), a systemic floral inhibitor or antiflorigen contributes to floral initiation. This chapter provides an overview of the different molecules that have been demonstrated to have florigenic or antiflorigenic functions in plants, and suggests possible directions for future research. PMID- 26374893 TI - Hormone cross-talk during seed germination. AB - Hormones are chemical substances that can affect many cellular and developmental processes at low concentrations. Plant hormones co-ordinate growth and development at almost all stages of the plant's life cycle by integrating endogenous signals and environmental cues. Much debate in hormone biology revolves around specificity and redundancy of hormone signalling. Genetic and molecular studies have shown that these small molecules can affect a given process through a signalling pathway that is specific for each hormone. However, classical physiological and genetic studies have also demonstrated that the same biological process can be regulated by many hormones through independent pathways (co-regulation) or shared pathways (cross-talk or cross-regulation). Interactions between hormone pathways are spatiotemporally controlled and thus can vary depending on the stage of development or the organ being considered. In this chapter we discuss interactions between abscisic acid, gibberellic acid and ethylene in the regulation of seed germination as an example of hormone cross talk. We also consider hormone interactions in response to environmental signals, in particular light and temperature. We focus our discussion on the model plant Arabidopsis thaliana. PMID- 26374894 TI - Comparison of plant hormone signalling systems. AB - Plant growth and development are controlled by nine structurally distinct small molecules termed phytohormones. Over the last 20 years, the molecular basis of their signal transduction, from receptors to transcription factors, has been dissected using mainly Arabidopsis thaliana and rice as model systems. Phytohormones can be broadly classified into two distinct groups on the basis of whether the subcellular localization of their receptors is in the cytoplasm or nucleus, and hence soluble, or membrane-bound, and hence insoluble. Soluble receptors, which control the responses to auxin, jasmonates, gibberellins, strigolactones and salicylic acid, signal either directly or indirectly via the destruction of regulatory proteins. Responses to abscisic acid are primarily mediated by soluble receptors that indirectly regulate the phosphorylation of targeted proteins. Insoluble receptors, which control the responses to cytokinins, brassinosteroids and ethylene, transduce their signal through protein phosphorylation. This chapter provides a comparison of the different components of these signalling systems, and discusses the similarities and differences between them. PMID- 26374895 TI - Can template-based protein models guide the design of sequence fitness for enhanced thermal stability of single domain antibodies? AB - We investigate the practical use of comparative (template-based) protein models in replica-exchange simulations of single-domain antibody (sdAb) chains to evaluate if the models can correctly predict in rank order the thermal susceptibility to unfold relative to experimental melting temperatures. The baseline model system is the recently determined crystallographic structure of a llama sdAb (denoted as A3), which exhibits an unusually high thermal stability. An evaluation of the simulation results for the A3 comparative model and crystal structure shows that, despite the overall low Calpha root-mean-square deviation between the two structures, the model contains misfolded regions that yields a thermal profile of unraveling at a lower temperature. Yet comparison of the simulations of four different comparative models for sdAb A3, C8, A3C8 and E9, where A3C8 is a design of swapping the sequence of the complementarity determining regions of C8 onto the A3 framework, discriminated among the sequences to detect the highest and lowest experimental melting transition temperatures. Further structural analysis of A3 for selected alanine substitutions by a combined computational and experimental study found unexpectedly that the comparative model performed admirably in recognizing substitution 'hot spots' when using a support-vector machine algorithm. PMID- 26374896 TI - Impact of an electronic alert notification system embedded in radiologists' workflow on closed-loop communication of critical results: a time series analysis. AB - INTRODUCTION: Optimal critical test result communication is a Joint Commission national patient safety goal and requires documentation of closed-loop communication among care providers in the medical record. Electronic alert notification systems can facilitate an auditable process for creating alerts for transmission and acknowledgement of critical test results. We evaluated the impact of a patient safety initiative with an alert notification system on reducing critical results lacking documented communication, and assessed potential overuse of the alerting system for communicating results. METHODS: We implemented an alert notification system-Alert Notification of Critical Results (ANCR)-in January 2010. We reviewed radiology reports finalised in 2009-2014 which lacked documented communication between the radiologist and another care provider, and assessed the impact of ANCR on the proportion of such reports with critical findings, using trend analysis over 10 semiannual time periods. To evaluate potential overuse of ANCR, we assessed the proportion of reports with non-critical results among provider-communicated reports. RESULTS: The proportion of reports with critical results among reports without documented communication decreased significantly over 4 years (2009-2014) from 0.19 to 0.05 (p<0.0001, Cochran-Armitage trend test). The proportion of provider-communicated reports with non-critical results remained unchanged over time before and after ANCR implementation (0.20 to 0.15, p=0.45, Cochran-Armitage trend test). CONCLUSIONS: A patient safety initiative with an alert notification system reduced the proportion of critical results among reports lacking documented communication between care providers. We observed no change in documented communication of non critical results, suggesting the system did not promote overuse. Future studies are needed to evaluate whether such systems prevent subsequent patient harm. PMID- 26374897 TI - The Triggering Receptor Expressed on Myeloid Cells 2 Binds Apolipoprotein E. AB - The triggering receptor expressed on myeloid cells 2 (TREM2) is an Ig-like V-type receptor expressed by populations of myeloid cells in the central nervous system and periphery. Loss-of-function mutations in TREM2 cause a progressive, fatal neurodegenerative disorder called Nasu-Hakola disease. In addition, a TREM2 R47H coding variant was recently identified as a risk factor for late-onset Alzheimer disease. TREM2 binds various polyanionic molecules but no specific protein ligands have been identified. Here we show that TREM2 specifically binds apolipoprotein E, a well established participant in Alzheimer disease. TREM2-Ig fusions efficiently precipitate ApoE from cerebrospinal fluid and serum. TREM2 also binds recombinant ApoE in solution and immobilized ApoE as detected by ELISA. Furthermore, the Alzheimer disease-associated R47H mutation, and other artificial mutations introduced in the same location, markedly reduced the affinity of TREM2 for ApoE. These findings reveal a link between two Alzheimer disease risk factors and may provide important clues to the pathogenesis of Nasu Hakola disease and other neurodegenerative disorders. PMID- 26374898 TI - High Resolution Structures of the Human ABO(H) Blood Group Enzymes in Complex with Donor Analogs Reveal That the Enzymes Utilize Multiple Donor Conformations to Bind Substrates in a Stepwise Manner. AB - Homologous glycosyltransferases alpha-(1->3)-N-acetylgalactosaminyltransferase (GTA) and alpha-(1->3)-galactosyltransferase (GTB) catalyze the final step in ABO(H) blood group A and B antigen synthesis through sugar transfer from activated donor to the H antigen acceptor. These enzymes have a GT-A fold type with characteristic mobile polypeptide loops that cover the active site upon substrate binding and, despite intense investigation, many aspects of substrate specificity and catalysis remain unclear. The structures of GTA, GTB, and their chimeras have been determined to between 1.55 and 1.39 A resolution in complex with natural donors UDP-Gal, UDP-Glc and, in an attempt to overcome one of the common problems associated with three-dimensional studies, the non-hydrolyzable donor analog UDP-phosphono-galactose (UDP-C-Gal). Whereas the uracil moieties of the donors are observed to maintain a constant location, the sugar moieties lie in four distinct conformations, varying from extended to the "tucked under" conformation associated with catalysis, each stabilized by different hydrogen bonding partners with the enzyme. Further, several structures show clear evidence that the donor sugar is disordered over two of the observed conformations and so provide evidence for stepwise insertion into the active site. Although the natural donors can both assume the tucked under conformation in complex with enzyme, UDP-C-Gal cannot. Whereas UDP-C-Gal was designed to be "isosteric" with natural donor, the small differences in structure imposed by changing the epimeric oxygen atom to carbon appear to render the enzyme incapable of binding the analog in the active conformation and so preclude its use as a substrate mimic in GTA and GTB. PMID- 26374899 TI - Apolipoprotein E Is a Ligand for Triggering Receptor Expressed on Myeloid Cells 2 (TREM2). AB - Several heterozygous missense mutations in the triggering receptor expressed on myeloid cells 2 (TREM2) have recently been linked to risk for a number of neurological disorders including Alzheimer disease (AD), Parkinson disease, and frontotemporal dementia. These discoveries have re-ignited interest in the role of neuroinflammation in the pathogenesis of neurodegenerative diseases. TREM2 is highly expressed in microglia, the resident immune cells of the central nervous system. Along with its adaptor protein, DAP12, TREM2 regulates inflammatory cytokine release and phagocytosis of apoptotic neurons. Here, we report apolipoprotein E (apoE) as a novel ligand for TREM2. Using a biochemical assay, we demonstrated high-affinity binding of apoE to human TREM2. The functional significance of this binding was highlighted by increased phagocytosis of apoE bound apoptotic N2a cells by primary microglia in a manner that depends on TREM2 expression. Moreover, when the AD-associated TREM2-R47H mutant was used in biochemical assays, apoE binding was vastly reduced. Our data demonstrate that apoE-TREM2 interaction in microglia plays critical roles in modulating phagocytosis of apoE-bound apoptotic neurons and establish a critical link between two proteins whose genes are strongly linked to the risk for AD. PMID- 26374900 TI - Calcium Signaling throughout the Toxoplasma gondii Lytic Cycle: A STUDY USING GENETICALLY ENCODED CALCIUM INDICATORS. AB - Toxoplasma gondii is an obligate intracellular parasite that invades host cells, creating a parasitophorous vacuole where it communicates with the host cell cytosol through the parasitophorous vacuole membrane. The lytic cycle of the parasite starts with its exit from the host cell followed by gliding motility, conoid extrusion, attachment, and invasion of another host cell. Here, we report that Ca(2+) oscillations occur in the cytosol of the parasite during egress, gliding, and invasion, which are critical steps of the lytic cycle. Extracellular Ca(2+) enhances each one of these processes. We used tachyzoite clonal lines expressing genetically encoded calcium indicators combined with host cells expressing transiently expressed calcium indicators of different colors, and we measured Ca(2+) changes in both parasites and host simultaneously during egress. We demonstrated a link between cytosolic Ca(2+) oscillations in the host and in the parasite. Our approach also allowed us to measure two new features of motile parasites, which were enhanced by Ca(2+) influx. This is the first study showing, in real time, Ca(2+) signals preceding egress and their direct link with motility, an essential virulence trait. PMID- 26374902 TI - Letter to the Editor: Atrioventricular plane displacement is not the sole mechanism of atrial and ventricular refill. PMID- 26374901 TI - Electron microscopic imaging revealed the flexible filamentous structure of the cell attachment protein P2 of Rice dwarf virus located around the icosahedral 5 fold axes. AB - The minor outer capsid protein P2 of Rice dwarf virus (RDV), a member of the genus Phytoreovirus in the family Reoviridae, is essential for viral cell entry. Here, we clarified the structure of P2 and the interactions to host insect cells. Negative stain electron microscopy (EM) showed that P2 proteins are monomeric and flexible L-shaped filamentous structures of ~20 nm in length. Cryo-EM structure revealed the spatial arrangement of P2 in the capsid, which was prescribed by the characteristic virion structure. The P2 proteins were visualized as partial rod shaped structures of ~10 nm in length in the cryo-EM map and accommodated in crevasses on the viral surface around icosahedral 5-fold axes with hydrophobic interactions. The remaining disordered region of P2 assumed to be extended to the radial direction towards exterior. Electron tomography clearly showed that RDV particles were away from the cellular membrane at a uniform distance and several spike-like densities, probably corresponding to P2, connecting a viral particle to the host cellular membrane during cell entry. By combining the in vitro and in vivo structural information, we could gain new insights into the detailed mechanism of the cell entry of RDV. PMID- 26374903 TI - Reply to "Letter to the Editor: Atrioventricular plane displacement is not the sole mechanism of atrial and ventricular refill". PMID- 26374904 TI - Linking Life Table and Predation Rate for Biological Control: A Comparative Study of Eocanthecona furcellata (Hemiptera: Pentatomidae) Fed on Spodoptera litura (Lepidoptera: Noctuidae) and Plutella xylostella (Lepidoptera: Plutellidae). AB - To better understand the predator-prey relationship and to compare predation rates, we studied the life table and predation rate of the predator Eocanthecona furcellata Wolff (Hemiptera: Pentatomidae) when reared on two major crucifer pests, Spodoptera litura (F.) (Lepidoptera: Noctuidae) and Plutella xylostella L. (Lepidoptera: Plutellidae). The net reproductive rate, intrinsic rate of increase, finite rate, and net predation rates of E. furcellata reared on P. xylostella were 292.4 offspring, 0.1389 d(-1), 1.1490 d(-1), and 644.1 third instars of P. xylostella, respectively. These values are significantly higher than those reared on S. litura, i.e., 272.3 offspring, 0.1220 d(-1), 1.1298 d( 1), and 863.1 third instars of S. litura. To evaluate the predation potential of E. furcellata fed on P. xylostella and S. litura, we combined both the growth rate and predation rate to calculate the finite predation rate (omega); our results showed that E. furcellata is an effective predator of both S. litura (omega = 1.6029) and P. xylostella (omega = 1.4277). PMID- 26374905 TI - The Short-Term Effect of Breathing Tasks Via an Incentive Spirometer on Lung Function Compared With Autogenic Drainage in Subjects With Cystic Fibrosis. AB - BACKGROUND: Forced expiration may assist secretion movement by manipulating airway dynamics in patients with cystic fibrosis (CF). Expiratory resistive breathing via a handheld incentive spirometer has the potential to control the expiratory flow via chosen resistances (1-8 mm) and thereby mobilize secretions and improve lung function. Our objective was to explore the short-term effect of using a resistive-breathing incentive spirometer on lung function in subjects with CF compared with the autogenic drainage technique. METHODS: This was a retrospective study. Subjects with CF performed 30-45 min of either the resistive breathing incentive spirometer (n = 40) or autogenic drainage (n = 32) technique on separate days. The spirometer encourages the patient to exhale as long as possible while maintaining a low lung volume. The autogenic drainage technique includes repetitive inspiratory and expiratory maneuvers at various tidal breathing magnitudes while exhalation is performed in a sighing manner. Spirometry was performed before and 20-30 min after the therapy. RESULTS: Use of a resistive-breathing incentive spirometer improved FVC and FEV1 by 5-42% in 26 subjects. The forced expiratory flow during the middle half of the FVC maneuver (FEF25-75%) improved by >20% in 9 (22%) subjects. FVC improved the most in subjects with an FEV1 of 40-60% of predicted. Improvements negatively correlated with baseline percent-of-predicted FVC values provided improvements were above 10% (r(2) = 0.28). Values improved in a single subjects using the autogenic drainage technique. CONCLUSIONS: These 2 techniques may allow lower thoracic pressures and assist in the prevention of central airway collapse. The resistive breathing incentive spirometer is a self-administered simple method that may aid airway clearance and has the potential to improve lung function as measured by FVC, FEV1, and FEF25-75% in patients with CF. PMID- 26374906 TI - Translation of Exercise Test Response to Training Intensity Using the Count Scale. AB - BACKGROUND: Exercise testing is recommended before prescribing individualized exercise intensity. However, there are few data demonstrating how exercise test responses are translated into individualized training intensity using a simple method. We previously developed a simple method to rate dyspnea called the count scale, including the count scale number (CSN) and count scale time. The purpose of this study was to assess the CSN for translation of exercise test response to training intensity. METHODS: Twenty-eight subjects (22 men and 6 women) with COPD age 66.6 +/- 8.22 y participated in 2 exercise sessions. During the first session, in which exercise was guided by the heart rate, the CSN and heart rate were obtained (ie, CSN1 and HR1) while the heart rate was increased by 20% compared with the resting heart rate. During the second session, exercise was guided by the CSN. When the CSN was close to the CSN1, the CSN and corresponding heart rate were recorded as CSN2 and HR2. Differences between CSN1 and CSN2 and between HR1 and HR2 were compared. The relationship between HR1 and HR2 was analyzed. Agreement between HR1 and HR2 was evaluated by Bland-Altman plots. RESULTS: No significant differences were seen between HR1 and HR2 (96 +/- 11 and 97 +/- 11, respectively; P = .14). A high correlation between HR1 and HR2 was found (r = 0.932, P < .001). The 95% CI for the difference between HR1 and HR2 was -1.2 to 8.5 beats/min. CONCLUSIONS: Exercise guided by the CSN alone could result in a given heart rate response, suggesting that the CSN is a simple and practical tool in translating exercise test results into individualized training intensity. With the CSN as the intensity indicator, patients can exercise safely and effectively. PMID- 26374907 TI - Response of Preterm Infants to 2 Noninvasive Ventilatory Support Systems: Nasal CPAP and Nasal Intermittent Positive-Pressure Ventilation. AB - BACKGROUND: Noninvasive ventilation (NIV) in preterm infants is currently applied using intermittent positive pressure (2 positive-pressure levels) or in a conventional manner (one pressure level). However, there are no studies in the literature comparing the chances of failure of these NIV methods. The aim of this study was to evaluate the occurrence of failure of 2 noninvasive ventilatory support systems in preterm neonates over a period of 48 h. METHODS: A randomized, prospective, clinical study was conducted on 80 newborns (gestational age < 37 weeks, birthweight < 2,500 g). The infants were randomized into 2 groups: 40 infants were treated with nasal CPAP and 40 infants with nasal intermittent positive-pressure ventilation (NIPPV). The occurrence of apnea, progression of respiratory distress, nose bleeding, and agitation was defined as ventilation failure. The need for intubation and re-intubation after failure was also observed. RESULTS: There were no significant differences in birth characteristics between groups. Ventilatory support failure was observed in 25 (62.5%) newborns treated with nasal CPAP and in 12 (30%) newborns treated with NIPPV, indicating an association between NIV failure and the absence of intermittent positive pressure (odds ratio [OR] 1.22, P < .05). Apnea (32.5%) was the main reason for nasal CPAP failure. After failure, 25% (OR 0.33) of the newborns receiving nasal CPAP and 12.5% (OR 0.14) receiving NIPPV required invasive mechanical ventilation. CONCLUSIONS: Ventilatory support failure was significantly more frequent when nasal CPAP was used. PMID- 26374908 TI - Use and Outcomes of Noninvasive Ventilation for Acute Respiratory Failure in Different Age Groups. AB - BACKGROUND: The prevalence of chronic disease and do-not-intubate status increases with age. Thus, we aimed to determine characteristics and outcomes associated with noninvasive ventilation (NIV) use for acute respiratory failure (ARF) in different age groups. METHODS: A database comprising prospective data collected on site on all adult patients with ARF requiring ventilatory support from 8 acute care hospitals in Massachusetts was used. RESULTS: From a total of 1,225 ventilator starts, overall NIV utilization, success, and in-hospital mortality rates were 22, 54, and 18% in younger (18-44 y); 34, 65, and 13% in middle-aged (45-64 y); 49, 68, and 17% in elderly (65-79 y); and 47, 76, and 24% in aged (>= 80 y) groups, respectively (P < .001, P = .08, and P = .11, respectively). NIV use for cardiogenic pulmonary edema and subjects with a do-not intubate order increased significantly with advancing age (25, 57, 57, and 74% and 7, 12, 18, and 31%, respectively, in the 4 age groups [P < .001 and P = .046, respectively]). For subjects receiving NIV with a do-not-intubate order, success and in-hospital mortality rates were similar in different age groups (P = .27 and P = .98, respectively). CONCLUSIONS: NIV use and a do-not-intubate status are more frequent in subjects with ARF >= 65 y than in those <65 y, especially for subjects with cardiogenic pulmonary edema. However, NIV success and mortality rates were similar between age groups. (ClinicalTrials.gov registration NCT00458926.). PMID- 26374909 TI - Usual Care Physiotherapy During Acute Hospitalization in Subjects Admitted to the ICU: An Observational Cohort Study. AB - BACKGROUND: Physiotherapists play an important role in the provision of multidisciplinary team-based care in the ICU. No studies have reported usual care respiratory management or usual care on the wards following ICU discharge by these providers. This study aimed to investigate usual care physiotherapy for ICU subjects during acute hospitalization. METHODS: One hundred subjects were recruited for an observational study from a tertiary Australian ICU. The frequency and type of documented physiotherapist assessment and treatment were extracted retrospectively from medical records. RESULTS: The sample had median (interquartile range) APACHE II score of 17 (13-21) and was mostly male with a median (interquartile range) age of 61 (49-73) y. Physiotherapists reviewed 94% of subjects in the ICU (median of 5 [3-9] occasions, median stay of 4.3 [3-7] d) and 89% of subjects in acute wards (median of 6 [2-12] occasions, median stay of 13.3 [6-28] d). Positioning, ventilator lung hyperinflation, and suctioning were the most frequently performed respiratory care activities in the ICU. The time from ICU admission until ambulation from the bed with a physiotherapist had a median of 5 (3-8) d. The average ambulation distance per treatment had a median of 0 (0-60) m in the ICU and 44 (8-78) m in the acute wards. Adverse event rates were 3.5% in the ICU and 1.8% on the wards. CONCLUSIONS: Subjects received a higher frequency of physiotherapy in the ICU than on acute wards. Consensus is required to ensure consistency in data collection internationally to facilitate comparison of outcomes. PMID- 26374910 TI - HIV Disrupts Human T Cells That Target Mycobacterial Glycolipids. AB - Single-cell analysis captures the heterogeneity of T-cell populations that target defined antigens. Human immunodeficiency virus (HIV) infection results in defects of antimycobacterial immunity, which remain poorly defined. We therefore recruited a small number of subjects, including those with latent and active M. tuberculosis infection, with or without concomitant HIV infection, and tracked the mycobacterial glycolipid-reactive T-cell repertoire by using CD1b tetramers. Glycolipid-reactive T cells expressed memory markers and the HIV coreceptors CD4 and CCR5; they were not detected in subjects with HIV-associated active M. tuberculosis infection. HIV infection may affect T cells that recognize mycobacterial glycolipids and influence immunity. PMID- 26374912 TI - Use of Existing Diagnostic Reverse-Transcription Polymerase Chain Reaction Assays for Detection of Ebola Virus RNA in Semen. AB - Sexual transmission of Ebola virus in Liberia has now been documented and associated with new clusters in regions previously declared Ebola free. Assays that have Emergency Use Authorization (EUA) and are routinely used to detect Ebola virus RNA in whole blood and plasma specimens at the Liberian Institute for Biomedical Research were tested for their suitability in detecting the presence of Ebola virus RNA in semen. Qiagen AVL extraction protocols, as well as the Ebola Zaire Target 1 and major groove binder quantitative reverse-transcription polymerase chain reaction assays, were demonstrably suitable for this purpose and should facilitate epidemiologic investigations, including those involving long term survivors of Ebola. PMID- 26374911 TI - INSIGHT FLU005: An Anti-Influenza Virus Hyperimmune Intravenous Immunoglobulin Pilot Study. AB - Hemagglutination inhibition (HAI) antibody responses to anti-influenza virus hyperimmune intravenous immunoglobulin (hIVIG) were characterized. Thirty-one patients with influenza during the 2013-2014 season were randomly assigned to receive 0.25 g/kg of hIVIG (n = 16) or placebo (n = 15). For hIVIG recipients, the ratio of geometric mean titers (1 hour after infusion/before infusion) was 4.00 (95% confidence interval [CI], 2.61-6.13) for 2009 pandemic influenza A(H1N1) and 1.76 (95% CI, 1.33-2.32) for influenza A(H3N2) and influenza B. Among patients with 2009 pandemic influenza A(H1N1), ratios for hIVIG (n = 9) versus placebo (n = 8) were higher 1 hour after infusion (3.9 [95% CI, 2.3-6.7]) and sustained through day 3 (2.0 [95% CI, 1.0-4.0]). hIVIG administration significantly increases HAI titer levels among patients with influenza, supporting the need to perform a clinical outcomes study. CLINICAL TRIALS REGISTRATION: NCT02008578. PMID- 26374913 TI - Towards prevention of autoantibody-positive rheumatoid arthritis: from lifestyle modification to preventive treatment. AB - Recent advances in research into the earliest phases of RA have provided additional insights into the processes leading from the healthy to the diseased state. These insights have opened the way for the development of preventive strategies for RA, which represents a significant paradigm shift from treatment to prevention and will have major implications for patients as well as society. It would be a huge step forward if clinical signs and symptoms, disability, impaired quality of life and the need for chronic immunosuppressive treatment could be prevented. RA can be seen as a prototypic autoimmune disease, and discoveries about the preclinical diseased state for RA could potentially facilitate research into prevention of other immune-mediated inflammatory diseases such as type 1 diabetes, SLE and multiple sclerosis. This review focuses on the current knowledge of factors contributing to the development of RA and discusses the opportunities for intervention. PMID- 26374914 TI - A SHORTCUT FORMULA FOR THE 230-MeV PROTON-INDUCED NEUTRON DOSE EQUIVALENT IN CONCRETE AFTER A METAL SHIELD, DERIVED FROM MONTE CARLO SIMULATIONS WITH MCNPX. AB - Monte Carlo simulations were performed with MCNPX to determine the neutron dose equivalent in thick concrete after a metal shield, a double-layered shielding configuration. In the simulations, a 230-MeV proton beam impinging on a copper target was used to produce the neutrons. For forward angles up to 30 degrees with respect to the proton beam, it is found that the neutron dose equivalent in thick concrete after a metal layer can be expressed in a single formula. This single formula being the neutron dose equivalent formula for a single thick concrete shield enhanced with an additional exponential term. The exponent of this additional exponential term is related to the relative macroscopic neutron removal cross section of the metal with respect to the concrete. The single formula found fits MCNPX data for the neutron dose equivalent in thick concrete after layers of metal ranging from beryllium to lead. First attempts were made to make this shortcut formula applicable to alloys and compounds of metals. PMID- 26374915 TI - Chronic Inotropic Therapy in the Current Era: Old Wines With New Pairings. PMID- 26374916 TI - Mapping the Terrain of Competing Risk Following Primary Prevention Defibrillator Implantation. PMID- 26374917 TI - Continuous-Flow Circulatory Support: The Achilles Heel of Current-Generation Left Ventricular Assist Devices? PMID- 26374918 TI - Tolvaptan in Patients Hospitalized With Acute Heart Failure: Rationale and Design of the TACTICS and the SECRET of CHF Trials. AB - Congestion is a primary reason for hospitalization in patients with acute heart failure (AHF). Despite inpatient diuretics and vasodilators targeting decongestion, persistent congestion is present in many AHF patients at discharge and more severe congestion is associated with increased morbidity and mortality. Moreover, hospitalized AHF patients may have renal insufficiency, hyponatremia, or an inadequate response to traditional diuretic therapy despite dose escalation. Current alternative treatment strategies to relieve congestion, such as ultrafiltration, may also result in renal dysfunction to a greater extent than medical therapy in certain AHF populations. Truly novel approaches to volume management would be advantageous to improve dyspnea and clinical outcomes while minimizing the risks of worsening renal function and electrolyte abnormalities. One effective new strategy may be utilization of aquaretic vasopressin antagonists. A member of this class, the oral vasopressin-2 receptor antagonist tolvaptan, provides benefits related to decongestion and symptom relief in AHF patients. Tolvaptan may allow for less intensification of loop diuretic therapy and a lower incidence of worsening renal function during decongestion. In this article, we summarize evidence for decongestion benefits with tolvaptan in AHF and describe the design of the Targeting Acute Congestion With Tolvaptan in Congestive Heart Failure Study (TACTICS) and Study to Evaluate Challenging Responses to Therapy in Congestive Heart Failure (SECRET of CHF) trials. PMID- 26374919 TI - First Successful Use of 2 Axial Flow Catheters for Percutaneous Biventricular Circulatory Support as a Bridge to a Durable Left Ventricular Assist Device. PMID- 26374920 TI - Letter by Monneret et al Regarding Article, "Cardiac Structure and Function Across the Glycemic Spectrum in Elderly Men and Women Free of Prevalent Heart Disease: The Atherosclerosis Risk In the Community Study". PMID- 26374921 TI - Commentary. PMID- 26374922 TI - Teamwork helps to prevent CAUTIs. PMID- 26374924 TI - Workouts and Weight. PMID- 26374923 TI - Insulin Innovations. PMID- 26374925 TI - Role of Protein Dynamics in Allosteric Control of the Catalytic Phosphoryl Transfer of Insulin Receptor Kinase. AB - The catalytic and allosteric mechanisms of insulin receptor kinase (IRK) are investigated by a combination of ab initio and semiempirical quantum mechanical and molecular mechanical (QM/MM) methods and classical molecular dynamics (MD) simulations. The simulations reveal that the catalytic reaction proceeds in two steps, starting with the transfer of a proton from substrate Tyr to the catalytic Asp1132, followed by the phosphoryl transfer from ATP to substrate Tyr. The enhancement of the catalytic rate of IRK upon phosphorylations in the enzyme's activation loop is found to occur mainly via changes to the free energy landscape of the proton transfer step, favoring the proton transfer in the fully phosphorylated enzyme. In contrast, the effects of the phosphorylations on the phosphoryl transfer are smaller. Equilibrium MD simulations show that IRK phosphorylations affect the protein dynamics of the enzyme before the proton transfer to Asp1132 with only a minor effect after the proton transfer. This finding is consistent with the large change in the proton transfer free energy and the smaller change in the free energy barrier of phosphoryl transfer found by QM/MM simulations. Taken together, the present results provide details on how IRK phosphorylation exerts allosteric control of the catalytic activity via modifications of protein dynamics and free energy landscape of catalytic reaction. The results also highlight the importance of protein dynamics in connecting protein allostery and catalysis to control catalytic activity of enzymes. PMID- 26374926 TI - Extraction, identification and antimicrobial activity of a new furanone, grifolaone A, from Grifola frondosa. AB - A furanone (1), (S)-methyl 2-(2-hydroxy-3,4-dimethyl-5-oxo-2,5-dihydrofuran-2 yl)acetate, was isolated from the edible mushroom Grifola frondosa. Mass spectrometry and NMR analyses were used to elucidate the structure of this compound, and its absolute configuration was determined using circular dichroism spectroscopy. Compound 1 exhibited specific antifungal activity against the plant pathogens, Fusarium oxysporum, Gibberella zeae and Piricularia oryzae and the opportunistic human pathogen, Pseudallescheria boydii, resulting in minimum inhibitory concentration values of 2.5, 2.5, 1.25 and 0.15 MUg/mL, respectively. In contrast, the furanone showed only weak activity towards Aspergillus spp., Candida albicans and several other fungal strains tested as well as no appreciable antibacterial activity. PMID- 26374928 TI - Sexual Excitability and Dysfunctional Coping Determine Cybersex Addiction in Homosexual Males. AB - Cybersex addiction (CA) has been mostly investigated in heterosexual males. Recent findings have demonstrated an association between CA severity and indicators of sexual excitability, and that coping by sexual behaviors mediated the relationship between sexual excitability and CA symptoms. The aim of this study was to test this mediation in a sample of homosexual males. Seventy-one homosexual males were surveyed online. Questionnaires assessed symptoms of CA, sensitivity to sexual excitation, pornography use motivation, problematic sexual behavior, psychological symptoms, and sexual behaviors in real life and online. Moreover, participants viewed pornographic videos and indicated their sexual arousal before and after the video presentation. Results showed strong correlations between CA symptoms and indicators of sexual arousal and sexual excitability, coping by sexual behaviors, and psychological symptoms. CA was not associated with offline sexual behaviors and weekly cybersex use time. Coping by sexual behaviors partially mediated the relationship between sexual excitability and CA. The results are comparable with those reported for heterosexual males and females in previous studies and are discussed against the background of theoretical assumptions of CA, which highlight the role of positive and negative reinforcement due to cybersex use. PMID- 26374927 TI - Use and Preference of Advice on Small Children's Food: Differences Between Parents From Ethnic Minority, Ethnic Majority, and Mixed Households. AB - The authors analyzed the influence of acculturation on parental attitudes to, and use of, different sources of health advice about young children's food in Denmark. Using combined ethnic position of the children's parents as a proxy for household acculturation, the authors conducted a postal survey of 2,511 households with young children (6 months to 3.5 years) occupying ethnic minority, ethnic majority, or ethnic mixed position. The analysis showed that the use of advice differed in the 3 groups. Households with ethnic minority status were more likely to use the child's grandparents, general practitioners, and hospital staff as information sources, while households with ethnic majority status were more likely to use mothers' peer groups and written material. In all types of household municipal public health nurses were relied on as a source of advice on young children's food, but households with ethnic minority status were more likely to find the advice obtained in this way incompatible with their family eating habits. Although existing dietary health communication strategies delivered by public health nurses appear to work well in all household types, parents from minority households seem to experience dilemmas. These may be related to their cultural and generational status at the time of receiving the advice. Adjustments to current communication strategies on young children's food are suggested. PMID- 26374929 TI - Tackling pollution by organic farming is capable of increasing fortified foods. AB - The global pollution stage is poisoning the biosphere and causing global temperatures to rise, necessitating a drastic change in the way man is dealing with nature. One change that may produce many beneficial effects on the biosphere and human health is the use of specific organic farming to produce food in a more integrated way in nature and to increase the capacity of man's own response. Despite many experts' opinion another way to deal with environmental contamination is possible: organic farming, which can increase man's ability to fortify foods. After more than 20 years working under this discipline, Bodegas Dagon is able to achieve the highest stilbenes concentrations (as resveratrol). Versus 14.3 mg/l, "Bodegas Dagon" wines contain resveratrol (HPLC and UV spectroscopy) up to 1611.73 +/- 72.66 mg/l, standing as world's potentially healthiest wine reported to date. PMID- 26374930 TI - Static and dynamic postural stability in veterans with combat-related mild traumatic brain injury. AB - Persistent post-concussive symptoms are reported by 10-15% of individuals who suffer mild traumatic brain injury (mTBI), but their basis is often uncertain. One such symptom is disequilibrium, a sensation of impaired balance during standing and walking. The hypothesis for this study was that this subjective symptom is associated with objective and measurable deficits in static and dynamic postural stability. An infrared motion tracking system was used to record body motion during quiet standing and in response to waist perturbations in fourteen veterans (age 22-40 years, 13 male) of the Operations Enduring Freedom (OEF) and Iraqi Freedom (OIF), who had a history of mTBI that occurred 7 months to 7 years prior to testing. We compared body sway between veterans with mTBI reporting persistent disequilibrium (TD, n=8) and those with no vestibular symptoms (n=6), as well as to a group of non-veterans with no balance symptoms (n=10). Static postural stability was reduced in TD veterans in comparison to each of the other two groups (p<0.0002), most notably on a compliant surface with eyes closed. The TD group also had decreased dynamic stability of the upper trunk (p<0.05) and enhanced postural oscillations (p<0.02) following waist perturbations. Our findings support a physiological basis for persistent disequilibrium after mTBI and are consistent with impaired vestibular processing. Disruption of semicircular canal inputs is unlikely to be the cause, as head impulse responses were normal in all groups. The unexpected finding of dynamic postural oscillations requires further study but may indicate enhanced instability in sensorimotor networks responsible for postural control. PMID- 26374931 TI - Nocturnal light pollution and underexposure to daytime sunlight: Complementary mechanisms of circadian disruption and related diseases. AB - Routine exposure to artificial light at night (ALAN) in work, home, and community settings is linked with increased risk of breast and prostate cancer (BC, PC) in normally sighted women and men, the hypothesized biological rhythm mechanisms being frequent nocturnal melatonin synthesis suppression, circadian time structure (CTS) desynchronization, and sleep/wake cycle disruption with sleep deprivation. ALAN-induced perturbation of the CTS melatonin synchronizer signal is communicated maternally at the very onset of life and after birth via breast or artificial formula feedings. Nighttime use of personal computers, mobile phones, electronic tablets, televisions, and the like--now epidemic in adolescents and adults and highly prevalent in pre-school and school-aged children--is a new source of ALAN. However, ALAN exposure occurs concomitantly with almost complete absence of daytime sunlight, whose blue-violet (446-484 nm lambda) spectrum synchronizes the CTS and whose UV-B (290-315 nm lambda) spectrum stimulates vitamin D synthesis. Under natural conditions and clear skies, day/night and annual cycles of UV-B irradiation drive corresponding periodicities in vitamin D synthesis and numerous bioprocesses regulated by active metabolites augment and strengthen the biological time structure. Vitamin D insufficiency and deficiency are widespread in children and adults in developed and developing countries as a consequence of inadequate sunlight exposure. Past epidemiologic studies have focused either on exposure to too little daytime UV-B or too much ALAN, respectively, on vitamin D deficiency/insufficiency or melatonin suppression in relation to risk of cancer and other, e.g., psychiatric, hypertensive, cardiac, and vascular, so-called, diseases of civilization. The observed elevated incidence of medical conditions the two are alleged to influence through many complementary bioprocesses of cells, tissues, and organs led us to examine effects of the totality of the artificial light environment in which humans reside today. Never have chronobiologic or epidemiologic investigations comprehensively researched the potentially deleterious consequences of the combination of suppressed vitamin D plus melatonin synthesis due to life in today's man-made artificial light environment, which in our opinion is long overdue. PMID- 26374932 TI - The Incidence of Trilateral Retinoblastoma: A Systematic Review and Meta Analysis. AB - PURPOSE: To estimate the incidence of trilateral retinoblastoma in patients with retinoblastoma. DESIGN: Systematic review and meta-analysis. METHODS: We searched Medline and Embase for scientific literature published between January 1966 and July 2015 that assessed trilateral retinoblastoma incidence. We used a random effects model for the statistical analyses. RESULTS: We included 23 retinoblastoma cohorts from 26 studies. For patients with bilateral retinoblastoma the unadjusted chance of developing trilateral retinoblastoma across all cohorts was 5.3% (95% confidence interval [CI]: 3.3%-7.7%); the chance of pineal trilateral retinoblastoma was 4.2% (95% CI: 2.6%-6.2%) and the chance of nonpineal trilateral retinoblastoma was 0.8% (95% CI: 0.4%-1.3%). In patients with hereditary retinoblastoma (all bilateral cases, and the unilateral cases with a family history or germline RB1 mutation) we found a trilateral retinoblastoma incidence of 4.1% (95% CI: 1.9%-7.1%) and a pineal trilateral retinoblastoma incidence of 3.7% (95% CI: 1.8%-6.2%). To reduce the risk of overestimation bias we restricted analysis to retinoblastoma cohorts with a minimum size of 100 patients, resulting in adjusted incidences of 3.8% (95% CI: 2.4%-5.4%), 2.9% (95% CI: 1.9%-4.2%), and 0.7% (95% CI: 0.3%-1.2%) for any, pineal, and nonpineal trilateral retinoblastoma, respectively, among patients with bilateral retinoblastoma. Among hereditary retinoblastoma we found an adjusted trilateral retinoblastoma incidence of 3.5% (95% CI: 1.2%-6.7%) and a pineal trilateral retinoblastoma incidence of 3.2% (95% CI: 1.4%-5.6%). CONCLUSION: The estimated incidence of trilateral retinoblastoma is lower than what is reported in previous literature, especially after exclusion of small cohorts that were subject to overestimation bias in this context. PMID- 26374933 TI - The protective role of maternal racial socialization for African American adolescents exposed to community violence. AB - Urban African American youth's disproportionate exposure to community violence and increased risk for its adverse consequences have heightened interest in identifying protective factors that mitigate the effects of community violence exposure for these youth. Thus, the present study examined whether maternal racial socialization messages protect African American adolescents against the adverse effects of community violence exposure. Participants were a community sample of African American adolescents (N = 106; mean age = 15.41 years) and their female guardians. For community-violence-exposed youth, maternal racial socialization messages protected against aggressive behaviors and depressive symptoms, such that maternal messages about cultural pride attenuated the association between community violence exposure and parent-reported aggressive behaviors, and cultural appreciation of legacy messages attenuated the association between community violence exposure and adolescent-reported depressive symptoms. Findings highlight the need to integrate race-relevant factors into preventive interventions targeting African American youth at risk for or exposed to community violence, and suggest that family interventions promoting parents' efficacy to implement racial socialization practices are useful for youth exposed to violence. PMID- 26374935 TI - Correction to Foster et al. (2009). PMID- 26374934 TI - Posttraumatic stress and emotion regulation in survivors of intimate partner violence. AB - Rates of posttraumatic stress symptoms (PTSS) are high among female survivors of intimate partner violence (IPV), and children of parents experiencing PTSS are at increased risk for emotional and behavioral problems. However, little is known about the factors that may explain this relation. We examined child's emotion regulation as a moderator and mother's emotion regulation as a mediator of the relation between mother PTSS and child adjustment. Sixty-four female survivors of IPV and their 6-12-year-old children participated. Mothers reported their own PTSS and their children's adjustment. Child emotion regulation was measured using respiratory sinus arrhythmia, a physiological index of emotion regulation. Mother's emotion regulation was measured from observer coding of the Parent Meta Emotion Interview (Katz & Gottman, 1986), which asked mothers about their awareness and regulation of emotion. Child emotion regulation moderated the relation between mother's PTSS and child depression and child PTSS. Mothers' total trauma symptom severity showed significant indirect effects on children's internalizing, externalizing, and total problems via mothers' emotion regulation. Results suggest that children's as well as mothers' emotion-regulation abilities represent factors that affect associations between maternal PTSS and child adjustment in families exposed to IPV. PMID- 26374936 TI - Parental causal attributions and emotions in daily learning situations with the child. AB - This study investigated the dynamics between the causal attributions parents reported daily for their children's success in learning situations and parental positive emotions. The sample consisted of 159 mothers and 147 fathers of 162 first graders (83 girls, 79 boys; aged from 6 to 7 years, M = 7.5 years, SD = 3.6 months). Parents filled in a structured diary questionnaire concerning their causal attributions and emotions over 7 successive days in the fall semester and again over 7 successive days in the spring semester. Multilevel analyses showed that both parental causal attributions and positive emotions varied more within parents (between days over the week) than between parents. Furthermore, mothers' positive emotions on a certain day predicted their causal attributions on that same day rather than vice versa. The higher the level of positive emotions parents reported in a specific day, the more they used effort and ability as causal attributions for their offspring's success on that same day. PMID- 26374937 TI - Buffering the negative effects of maternal alcohol problems on child behavior. AB - Our objective was to examine how mothers' warmth can protect children from the negative effects of maternal alcohol problems on children's externalizing behavior and, alternately, how harsh parenting can exacerbate the problem. We used data from 1,563 families eligible for Early Head Start and assessed when children were age 5 and again at age 11. We examined whether mothers' warmth or harsh parenting at age 5 moderated the effect of maternal alcohol problems on children's behavior problems at age 11. Results indicated that mothers' symptoms of alcohol problems when children were age 5 predicted greater externalizing behavior problems (aggression and rule breaking) when children were age 11. Aggression and rule-breaking behaviors, externalizing behaviors commonly associated with maternal alcohol problems, were lessened when mothers were warm and did not engage in harsh parenting techniques. Our findings highlight the importance of positive parenting techniques in high-risk families. PMID- 26374938 TI - Veteran-child communication about parental PTSD: A mixed methods pilot study. AB - The majority of adults with posttraumatic stress disorder (PTSD) are parents. Parents with PTSD report lower levels of parenting satisfaction, poorer parent child relationships, and elevated incidence of child distress and behavioral problems in comparison with parents without PTSD. Although literature exists regarding parent-child communication about serious mental illness and physical health problems, research has yet to examine this communication regarding parental PTSD. This 3-site, mixed methods study involved 19 veteran parents who had a diagnosis of PTSD; participants were recruited from VA medical centers. Veterans participated in focus groups or individual interviews and completed questionnaires, responding to questions about motivations and barriers for disclosure of their PTSD to their children, the content of such disclosure, experiences at the VA as a parent, and desired VA family resources. Although many veterans described a desire to talk with their children about PTSD, they experience many barriers to doing so, including both personal reservations and feelings (e.g., avoidance of discussing PTSD, shame) and concerns about the consequences of disclosure on their children (e.g., child distress, loss of child's respect for veteran). Regarding veterans' experience at the VA, 21% reported that none of their providers had assessed if they have children, and 21% experienced the VA system as not welcoming to them as parents, citing both logistical issues (e.g., lack of childcare) and provider neglect of parenting concerns. Veterans indicated they would like the VA to offer parenting classes, workshops for families, child care, and family therapy. PMID- 26374939 TI - Family enmeshment, adolescent emotional dysregulation, and the moderating role of gender. AB - Enmeshment plays a key role in many families' dysfunctional interactions and may be especially detrimental for adolescents. Sixty-four adolescents completed ratings of family enmeshment, perceived distress tolerance, an interpersonal challenge task, and mood ratings before and immediately after the task. Before and during the challenge task, adolescents' respiratory sinus arrhythmia (an indicator of cardiac vagal tone) was recorded. Associations were tested between adolescents' perceptions of family enmeshment and 3 aspects of adolescent emotional dysregulation. Adolescents who perceived higher family enmeshment also demonstrated greater emotional dysregulation in several domains: negative global appraisals of distress tolerance, stronger increase in subjective negative mood from baseline to postchallenge, lower baseline vagal tone, and vagal augmentation during the challenge task. Gender differences also emerged, such that girls reported more negative distress appraisals overall and enmeshed boys showed greater emotional dysregulation across analyses. Findings are discussed in terms of how clinicians may dynamically assess and treat enmeshment and emotional dysregulation in families with male and female adolescents. PMID- 26374940 TI - Protective spin-labeled fluorenes maintain amyloid beta peptide in small oligomers and limit transitions in secondary structure. AB - Alzheimer's disease is characterized by the presence of extracellular plaques comprised of amyloid beta (Abeta) peptides. Soluble oligomers of the Abeta peptide underlie a cascade of neuronal loss and dysfunction associated with Alzheimer's disease. Single particle analyses of Abeta oligomers in solution by fluorescence correlation spectroscopy (FCS) were used to provide real-time descriptions of how spin-labeled fluorenes (SLFs; bi-functional small molecules that block the toxicity of Abeta) prevent and disrupt oligomeric assemblies of Abeta in solution. Furthermore, the circular dichroism (CD) spectrum of untreated Abeta shows a continuous, progressive change over a 24-hour period, while the spectrum of Abeta treated with SLF remains relatively constant following initial incubation. These findings suggest the conformation of Abeta within the oligomer provides a complementary determinant of Abeta toxicity in addition to oligomer growth and size. Although SLF does not produce a dominant state of secondary structure in Abeta, it does induce a net reduction in beta secondary content compared to untreated samples of Abeta. The FCS results, combined with electron paramagnetic resonance spectroscopy and CD spectroscopy, demonstrate SLFs can inhibit the growth of Abeta oligomers and disrupt existing oligomers, while retaining Abeta as a population of smaller, yet largely disordered oligomers. PMID- 26374941 TI - On-demand drug delivery from local depots. AB - Stimuli-responsive polymeric depots capable of on-demand release of therapeutics promise a substantial improvement in the treatment of many local diseases. These systems have the advantage of controlling local dosing so that payload is released at a time and with a dose chosen by a physician or patient, and the dose can be varied as disease progresses or healing occurs. Macroscale drug depot can be induced to release therapeutics through the action of physical stimuli such as ultrasound, electric and magnetic fields and light as well as through the addition of pharmacological stimuli such as nucleic acids and small molecules. In this review, we highlight recent advances in the development of polymeric systems engineered for releasing therapeutic molecules through physical and pharmacological stimulation. PMID- 26374942 TI - Nitric oxide-releasing polysaccharide derivative exhibits 8-log reduction against Escherichia coli, Acinetobacter baumannii and Staphylococcus aureus. AB - Health-care associated infections (HAIs) and the increasing number of antibiotic resistant bacteria strains remain significant public health threats worldwide. Although the number of HAIs has decreased by using improved sterilization protocols, the cost related to HAIs is still quantified in billions of dollars. Furthermore, the development of multi-drug resistant strains is increasing exponentially, demonstrating that current treatments are inefficient. Thus, the quest for new methods to eradicate bacterial infection is increasingly important in antimicrobial, drug delivery and biomaterials research. Herein, the bactericidal activity of a water-soluble NO-releasing polysaccharide derivative was evaluated in nutrient broth media against three bacteria strains that are commonly responsible for HAIs. Data confirmed that this NO-releasing polysaccharide derivative induced an 8-log reduction in bacterial growth after 24h for Escherichia coli, Acinetobacter baumannii and Staphylococcus aureus. Additionally, the absence of bacteria after 72h of exposure to NO illustrates the inability of the bacteria to recover and the prevention of biofilm formation. The presented 8-log reduction in bacterial survival after 24h is among the highest reduction reported for NO delivery systems to date, and reaches the desired standard for industrially-relevant reduction. More specifically, this system represents the only water-soluble antimicrobial to reach such a significant bacterial reduction in nutrient rich media, wherein experimental conditions more closely mimic the in vivo environment than those in previous reports. Furthermore, the absence of bacterial activity after 72h and the versatility of using a water-soluble compound suggest that this NO-releasing polysaccharide derivative is a promising route for treating HAIs. PMID- 26374943 TI - Cortisol Concentrations in Well-Regulated Dogs with Hyperadrenocorticism Treated with Trilostane. AB - BACKGROUND: There are no clear treatment guidelines for dogs with clinically well regulated hyperadrenocorticism in which serum cortisol concentrations before and after an ACTH stimulation test performed 3-6 hours after trilostane administration are < 2.0 MUg/dL. OBJECTIVE: To determine if serum cortisol concentrations measured before (Pre1) and after (Post1) ACTH stimulation at 3-6 hours after trilostane administration are significantly lower than cortisol concentrations measured before (Pre2) and after (Post2) ACTH stimulation 9-12 hours after trilostane administration, in a specific population of dogs with clinically well-regulated hyperadrenocorticism and Pre1 and Post1 <2 MUg/dL. ANIMALS: Thirteen client-owned dogs with clinically well-regulated hyperadrenocorticism and Pre1 and Post1 serum cortisol concentrations <2.0 MUg/dL 3-6 hours after trilostane administration. METHODS: Prospective study. Dogs had a second ACTH stimulation test performed 9-12 hours after trilostane administration, on the same day of the first ACTH stimulation test. Cortisol concentrations before and after ACTH stimulation were compared using a paired t test. RESULTS: Cortisol concentrations before (1.4 +/- 0.3 MUg/dL) and after the first stimulation (1.5 +/- 0.3 MUg/dL, mean +/- SD) were significantly lower than cortisol concentration before the second stimulation (3.3 +/- 1.6 MUg/dL, P = .0012 each). Cortisol concentration before the first stimulation was also significantly lower than cortisol concentration after the second stimulation (5.3 +/- 2.4 MUg/dL, P = .0001). CONCLUSIONS AND CLINICAL IMPORTANCE: In dogs with clinically well-regulated, trilostane-treated, hyperadrenocorticism, and cortisol concentrations <2 MUg/dL before and after the first stimulation, a second ACTH stimulation test performed 9-12 hours after treatment can result in higher cortisol concentrations that could support continued trilostane treatment. PMID- 26374944 TI - Unraveling of cross talk between Ca(2+) and ROS regulating enzymes in Anabaena 7120 and ntcA mutant. AB - In order to understand a cross talk between Ca(2+) and ROS regulating enzymes and the possible involvement of ntcA gene, Anabaena sp. PCC 7120 and its derivative ntcA mutant grown in varied levels of calcium chloride (0, 1, 10, and 100 mM) have been investigated. Scanning Electron Microscopy showed abnormal structure formation at high calcium concentration (100 mM) both in wild type and mutant. Fv /Fm values suggested that 100 mM calcium concentration was detrimental for photosynthetic apparatus. SOD, catalase, APX, GR, and peroxidase activity were found to be maximum for 100 mM and minimum for 1 mM of exogenously supplied calcium salt. NADPH contents were higher for wild type than mutant. RAPD-PCR and SDS-PAGE analysis revealed a difference in DNA as well as proteome pattern with changes in calcium chloride regime. Prominent bands of approximately 70, 33, 21, and 14 kDa expressed in the wild type served as the marker polypeptide bands under calcium supplementation. Results suggest that higher levels of calcium ion disturb the cellular homeostasis generating ROS, thereby inducing enhanced levels of antioxidative enzymes. Further, data also suggests possible involvement of ntcA gene in cross talk between calcium ion and ROS regulating enzymes. PMID- 26374945 TI - Monocytic delivery of therapeutic oxygen bubbles for dual-modality treatment of tumor hypoxia. AB - Photodynamic therapy (PDT) is a powerful technique photochemically tailored for activating apoptosis of malignant cells. Although PDT has shown promise in several clinical applications, malignant cells in hypoxic regions are often resistant to PDT due to the transport limitation of therapeutics and the oxygen dependent nature of PDT. Herein, we present an innovative strategy for overcoming the limits of PDT in tumor hypoxia using bone marrow-derived monocytes as cellular vehicles for co-transport of oxygen and red light activatable photosensitizer, chlorin e6 (Ce6). Superparamagnetic iron oxide nanoparticle/Ce6/oxygen-loaded polymer bubbles were prepared and internalized into tumortropic monocytes. These functional bubbles were found harmless to cellular hosts without external triggers. Nevertheless, the therapeutic monocytes exhibited a superior performance in inhibiting tumor growth on Tramp-C1 tumor bearing mice (C57BL/6J) upon the treatments of tumors with high frequency magnetic field and red light laser (660 nm). Histological examinations of the tumor sections confirmed the successful cellular transport of therapeutic payloads to tumor hypoxia and the pronounced antitumor effect elicited by combined hyperthermia/photodynamic therapy along with the additional oxygen supply. This work demonstrates that this oxygen/therapeutic co-delivery via tumortropic monocytes toward tumor hypoxia is promising for improving PDT efficacy. PMID- 26374947 TI - The Association of Early and Recent Psychosocial Life Stress With Leukocyte Telomere Length. AB - OBJECTIVES: Chronic exposure to psychosocial stressors is related to worse somatic health. This association applies both to stressors early in life, such as childhood adversities, and more recent life stress, such as stressful life events. This study examined whether accelerated telomere shortening, as an indicator of cellular aging, might be an explanatory mechanism. METHODS: We examined whether childhood adversities and recent stressful life events were associated with shorter telomeres in 2936 participants (mean [standard deviation] age = 41.8 [13.1] years, 66% women, 57% current depression) of the Netherlands Study of Depression and Anxiety. Telomeres are specialized nucleic acid-protein complexes at the ends of linear DNA that shorten with age; telomere length (TL) was measured with quantitative polymerase chain reaction. RESULTS: Childhood life events (beta = .004, p = .805) and childhood trauma (beta = -.023, p = .205) were not related to shorter TL. However, we found negative associations between recent stressful life events and TL. Persons had shorter telomeres if they reported more stressful life events in the past year (beta = -.039, p = .028) and 1 to 5 years ago (beta = -.042, p = .018, adjusted for sociodemographics). The relationship between stressful life events and TL became borderline significant when further adjusted for smoking status. No associations with TL were found when stressful life events occurred more than 6 years ago (p > .10). CONCLUSIONS: Results show that recent stressful life events are associated with shorter TL. This association is not observed for psychosocial stressors that occur earlier in life. Whether these results are indicative of physiological resiliency remains to be explored by future longitudinal research. PMID- 26374946 TI - Role of xanthine oxidoreductase in the anti-thrombotic effects of nitrite in rats in vivo. AB - The mechanisms underlying nitrite-induced effects on thrombosis and hemostasis in vivo are not clear. The goal of the work described here was to investigate the role of xanthine oxidoreductase (XOR) in the anti-platelet and anti-thrombotic activities of nitrite in rats in vivo. Arterial thrombosis was induced electrically in rats with renovascular hypertension by partial ligation of the left renal artery. Sodium nitrite (NaNO2, 0.17 mmol/kg twice daily for 3 days, p.o) was administered with or without one of the XOR-inhibitors: allopurinol (ALLO) and febuxostat (FEB) (100 and 5 mg/kg, p.o., for 3 days). Nitrite treatment (0.17 mmol/kg), which was associated with a significant increase in NOHb, nitrite/nitrate plasma concentration, resulted in a substantial decrease in thrombus weight (TW) (0.48 +/- 0.03 mg vs. vehicle [VEH] 0.88 +/- 0.08 mg, p < 0.001) without a significant hypotensive effect. The anti-thrombotic effect of nitrite was partially reversed by FEB (TW = 0.63 +/- 0.06 mg, p < 0.05 vs. nitrites), but not by ALLO (TW = 0.43 +/- 0.02 mg). In turn, profound anti platelet effect of nitrite measured ex vivo using collagen-induced whole-blood platelet aggregation (70.5 +/- 7.1% vs. VEH 100 +/- 4.5%, p < 0.05) and dynamic thromboxaneB2 generation was fully reversed by both XOR-inhibitors. In addition, nitrite decreased plasminogen activator inhibitor-1 concentration (0.47 +/- 0.13 ng/ml vs. VEH 0.62 +/- 0.04 ng/ml, p < 0.05) and FEB/ALLO reversed this effect. In vitro the anti-platelet effect of nitrite (1 mM) was reversed by FEB (0.1 mM) under hypoxia (0.5%O2) and normoxia (20%O2). Nitrite treatment had no effect on coagulation parameters. In conclusion, the nitrite-induced anti-platelet effect in rats in vivo is mediated by XOR, but XOR does not fully account for the anti thrombotic effects of nitrite. PMID- 26374948 TI - Preconception Maternal Bereavement and Infant and Childhood Mortality: A Danish Population-Based Study. AB - OBJECTIVES: Preconception maternal bereavement may be associated with an increased risk for infant mortality, although these previously reported findings have not been replicated. We sought to examine if the association could be replicated and explore if risk extended into childhood. METHODS: Using a Danish population-based sample of offspring born 1979 to 2009 (N = 1,865,454), we analyzed neonatal (0-28 days), postneonatal infant (29-364 days), and early childhood (1-5 years) mortality after maternal bereavement in the preconception (6-0 months before pregnancy) and prenatal (between conception and birth) periods. Maternal bereavement was defined as death of a first-degree relative of the mother. Analyses were conducted using logistic and log-linear Poisson regressions that were adjusted for offspring, mother, and father sociodemographic and health factors. RESULTS: We identified 6541 (0.004%) neonates, 3538 (0.002%) postneonates, and 2132 (0.001%) children between the ages of 1 and 5 years who died. After adjusting for covariates, bereavement during the preconception period was associated with increased odds of neonatal (adjusted odds ratio = 1.87, 95% confidence interval = 1.53-2.30) and postneonatal infant mortality (adjusted odds ratio = 1.52, 95% confidence interval = 1.15-2.02). Associations were timing specific (6 months before pregnancy only) and consistent across sensitivity analyses. Bereavement during the prenatal period was not consistently associated with increased risk of offspring mortality; however, this may reflect relatively low statistical power. CONCLUSIONS: Results support and extend previous findings linking bereavement during the preconception period with increased odds of early offspring mortality. The period immediately before pregnancy may be a sensitive period with potential etiological implications and ramifications for offspring mortality. PMID- 26374949 TI - Effects of recombinant human Bone Morphogenetic Protein-2 (rhBMP-2) in grade III open tibia fractures treated with unreamed nails-A clinical and health-economic analysis. AB - Recombinant human Bone Morphogenetic Protein-2 (rhBMP-2) is licensed in Europe for open tibia fractures treated with unreamed nails. However, there is limited data available on the specific use of rhBMP-2 in combination with unreamed nails for open tibia fractures. The intention of the current study was to evaluate the medical and health-economic effects of rhBMP-2 in Gustilo-Anderson grade III open tibia fractures treated with unreamed nails based on individual patient data from two previously published studies. Linear regression analysis was performed on raw data of 90 patients that were either treated by standard of care with soft tissue management and unreamed nailing (SOC group) (n=50) or with rhBMP-2 in addition to soft tissue management and unreamed nailing (rhBMP-2 group) (n=40). For all types of revision, a significant lower percentage of patients (27.5%) of the rhBMP-2 group had to be revised compared to 48% of the patients of the SOC group (p=0.04). When only invasive secondary interventions such as bone grafting and nail exchange were considered, there was also a statistically significant reduction in the rhBMP-2 group with a revision rate of 10.0% (4 of 40 patients) compared to the SOC group with a revision rate of 28.0% (14 of 50 patients) (p=0.01). Mean fracture healing time of 228 days in the rhBMP-2 compared to 266 days in the SOC group was not statistically significant (p=0.24). Health-economic analysis based on a societal perspective with calculation of overall treatment costs after initial surgery and including productivity losses revealed savings of ?6,239 per patient for Germany and ?4,752 for the UK in favour of rhBMP-2 which was mainly driven by reduction of productivity losses. In conclusion, rhBMP-2 reduces secondary interventions in patients with grade III open tibia fractures treated with an unreamed nail and its use leads to financial savings for Germany and the UK from a societal perspective. PMID- 26374950 TI - What's new in antifungals: an update on the in-vitro activity and in-vivo efficacy of new and investigational antifungal agents. AB - PURPOSE OF REVIEW: Despite the availability of new antifungals and improved antifungal formulations, there is a continued need for the development of new drugs to treat invasive fungal infections. In high-risk populations, including heavily immunocompromised patients, those with multiple comorbidities, and patients in intensive care settings, invasive fungal infections remain a significant problem, and are associated with high morbidity and mortality. In addition, concerns of increasing antifungal resistance to available agents further highlight the need for new drugs to treat these infections. RECENT FINDINGS: Recent studies have reported potent in-vitro activity for several investigational agents, including both yeasts and moulds. This in-vitro activity has also translated into in-vivo efficacy in animal models of various invasive fungal infections, including those caused by isolates that are resistant to clinically available agents. These agents include those with mechanisms of action similar to available agents and those that target fungi by novel means. SUMMARY: Several new antifungal agents are currently in various stages of development. This is promising, as there is a continued need for new agents to treat invasive fungal infections. Which ones will receive approval for clinical use and their impact in patients with these infections remain unknown. PMID- 26374951 TI - Can mortality of cancer patients with fever and neutropenia be improved? AB - PURPOSE OF REVIEW: Neutropenic fever is the most common infective complication in patients receiving cytotoxic chemotherapy, and may result in severe sepsis, septic shock and mortality. Advancements in approaches to empiric antimicrobial therapy and prophylaxis have resulted in improved outcomes. Mortality may, however, still be as high as 50% in high-risk cancer populations. The objective of this review is to summarize factors associated with reduced mortality in patients with neutropenic fever, highlighting components of clinical care with potential for inclusion in quality improvement programs. RECENT FINDINGS: Risks for mortality are multifactorial, and include patient, disease and treatment related factors. Historically, guidelines for management of neutropenic fever have focused upon antimicrobial therapy. There is, however, a recognized need for early identification of sepsis to enable timely administration of antibiotic therapy and for this to be integrated with a whole of systems approach within healthcare facilities. Use of Systemic Inflammatory Response Syndrome criteria is beneficial, but validation is required in neutropenic fever populations. SUMMARY: In the context of emerging and increasing infections because of antimicrobial resistant bacteria in patients with neutropenic fever, quality improvement initiatives to reduce mortality must encompass antimicrobial stewardship, early detection of sepsis, and use of valid tools for clinical assessment. C-reactive protein and procalcitonin hold potential for inclusion into clinical pathways for management of neutropenic fever. PMID- 26374952 TI - Valacyclovir combined with artesunate or rapamycin improves the outcome of herpes simplex virus encephalitis in mice compared to antiviral therapy alone. AB - Despite antiviral therapy, the mortality rate of herpes simplex virus encephalitis (HSE) remains high and many surviving patients harbor neurological sequelae. Although viral replication is responsible for substantial neurological damages, an exaggerated inflammatory response could also contribute to this process. Artesunate (ART) and rapamycin (RAPA) have shown some benefits in the treatment of herpes simplex virus infections. Herein, we evaluated the benefit of combining ART or RAPA with valacyclovir (VACV) in a murine model of HSE. Infected mice were treated with VACV (1mg/mL in drinking water) from day 3 post-infection (p.i.) combined or not with daily intraperitoneal administration of ART (30mg/kg) or RAPA (20mg/kg) from days 4 to 13 p.i. Viral load, infectious titers, cytokine and chemokine levels were measured in brain homogenates on days 5, 7 and 9. The survival rates of mice treated with VACV and ART or RAPA were higher than with VACV alone (71.9% versus 43.2% for ART and 66.7% versus 43.2% for RAPA; both P?0.05) but no significant difference was seen in the brain viral loads. Levels of IL-1beta, IL-2 (both P?0.05), IL-6, IFN-gamma (both P?0.01), CCL2 (P?0.01), CCL3 and CCL4 (both P?0.05) were reduced in mice treated with VACV combined with ART versus VACV alone. Levels of IL-6, IL-1beta and IFN-gamma slightly increased on day 7 in mice treated with VACV combined with RAPA compared to VACV alone and then decreased on day 9. Our results suggest that immunomodulatory compounds such as ART or RAPA could benefit antiviral therapy in HSE. PMID- 26374953 TI - Self-injury Is the Eighth Leading Cause of Death in the United States: It Is Time to Pay Attention. PMID- 26374954 TI - Effect of Bariatric Surgery vs Medical Treatment on Type 2 Diabetes in Patients With Body Mass Index Lower Than 35: Five-Year Outcomes. AB - IMPORTANCE: It has been well recognized that metabolic surgery has short-term benefits for mildly obese patients with type 2 diabetes mellitus (T2DM), but how long these effects can be sustained is uncertain. OBJECTIVE: To compare the 5 year efficacy between gastrointestinal metabolic surgery and medical treatment on glycemic control and diabetes remission in patients with T2DM and body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) lower than 35. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study compares long-term outcomes for mildly obese patients with T2DM receiving metabolic surgery (n = 52) vs medical treatment (n = 299). The surgical group, enrolled from August 20, 2007, to June 25, 2008, and followed up through December 31, 2013, received standard sleeve gastrectomy (n = 19) or bypass (n = 33) procedures in a regional hospital. The medical group, selected from a nationwide community cohort that was recruited from August 27, 2003, to December 31, 2005, and followed up through December 31, 2012, was matched with the surgical group by age, BMI, and diabetes duration. MAIN OUTCOMES AND MEASURES: Glycated hemoglobin (HbA1c) reduction and prolonged complete and partial diabetes remission (defined as HbA1c <6.0% and 6.0%-6.5% of total hemoglobin [Hb; to convert to proportion of total Hb, multiply by 0.01], respectively, for those who were exempted from any antidiabetic drugs for 5 years). RESULTS: At the end of the fifth year, the surgical group had a mean weight loss of 21.0% (from a mean [SD] BMI of 31.0 [2.4] to 24.5 [2.7]), their mean (SD) HbA1c decreased from 9.1% (2.1%) to 6.3% (1.1%) of total Hb, 18 participants (36.0%) had complete remission, 14 (28.0%) had partial remission, 1 (1.9%) died, and 1 (1.9%) had end-stage renal disease. In the same follow-up period in the medical group, 3 (1.2%) had complete remission, 4 (1.6%) had partial remission, 9 (3.0%) died, and 2 (0.7%) had end stage renal disease; their mean HbA1c remained around 8% of total Hb (mean [SD], 8.1% [1.8%] of total Hb at baseline and 8.0% [1.6%] of total Hb at 5 years), and BMI also stayed similar (mean [SD], 29.1 [2.4] at baseline and 28.8 [2.6] at 5 years). The HbA1c reduction and complete and partial remission rates were all significantly larger in the surgical group as compared with the medical group (all P < .001). However, the mortality rate and end-stage renal disease incidence were not significantly different in these 2 comparison groups (P = .66 and .37, respectively). CONCLUSIONS AND RELEVANCE: For mildly obese patients with T2DM, the improvement in glycemic control from metabolic surgery lasts at least 5 years. However, the survival benefit and lifelong adverse outcomes require more than 5 years to be established. PMID- 26374955 TI - Prevalence of chronic kidney disease and administration of RA-related drugs in patients with RA: The NinJa 2012 study in Japan. AB - OBJECTIVES: To estimate the prevalence of chronic kidney disease in patients with rheumatoid arthritis (RA) and the administration of disease-modifying anti rheumatic-drugs (DMARDs), using data from the National Database of Rheumatic Disease by iR-net in Japan (NinJa) 2012 study. METHODS: From a total of 11,940 RA patients, 7135 who underwent an estimated glomerular filtration rate (eGFR) test were studied. Renal dysfunction staging was assessed using Japanese eGFR equations and classified according to the Kidney Disease Improving Global Outcomes 2012 clinical practice guideline. RESULTS: The prevalence of GFR stages was as follows: stage G1, 25.4%; stage G2, 55.9%; stage G3, 17.5%; stage G4, 0.8%; and stage G5, 0.2%. Overall, 92.7% of patients received at least one DMARD. Sulfasalazine, tacrolimus, and biologics (except inflixmab) were administered in all GFR stages. Methotrexate was not prescribed in patients with stage G5, but methotrexate 3.5 mg/week (mean) was prescribed in four patients (6.8%) with stage G4. Non-steroidal anti-inflammatory drugs and glucocorticoids were prescribed in 40.5% and 43.7% of patients, respectively. CONCLUSION: The prevalence of kidney disease in this large sample of RA patients was higher than that in the general population, and the results suggest that RA patients with renal dysfunction require careful drug selection. PMID- 26374956 TI - Clinical Research Abstracts of the British Equine Veterinary Association Congress 2015. AB - REASONS FOR PERFORMING STUDY: Equine gastric glandular disease (EGGD) is a common condition, for which the underlying pathophysiology is undetermined. Endoscopic mucosal biopsies have been proposed as a method for adapting therapy. OBJECTIVES: To evaluate diagnostic information obtained from endoscopic mucosal biopsies. STUDY DESIGN: Prospective, experimental study. METHODS: Twenty-one horses undergoing elective humane slaughter were subjected to gross examination of the glandular mucosa. Glandular pathology was graded using EGUS Council guidelines from digital camera images. Mucosal biopsies were obtained using a 'single-bite' (1.8 mm; A and 2.4 mm; B) or 'double bite' technique (2.4 mm; C) using endoscopic biopsy instruments. Tissue was formalin fixed, processed and stained using standard protocols. Inflammatory infiltrates visualised histologically were graded (mild, moderate or severe) and compared with ulcer grade. Full thickness biopsies were also obtained adjacent to the biopsy site and of other visual lesions and inflammatory cell counts were compared with mucosal biopsies using ICC. RESULTS: Full thickness samples were artefact free and allowed visualisation of all layers. Mucosal biopsy samples contained mucosa in all samples, submucosa in 55% (C), 61% (A) and 66% (B) of samples and glands in 50% (B), 66% (A) and 100% (C). Samples from A were too small for histological assessment (33%) and tissue damage was commonly seen in A and B (n = 8 and n = 10) when compared with C (n = 3). Horses with normal glandular appearance (grade 0; n = 7) mostly demonstrated mild gastritis (n = 5). Severe gastritis was identified in mild EGGD (grade 1/2), whilst mild and moderate gastritis was identified in all EGGD grades. There was no histological evidence of ulceration or erosion. There was poor agreement between cell numbers and sampling techniques (ICC<0.29). CONCLUSIONS: These data show lack of ulcerative pathology and instead inflammation in EGGD. Lesion appearance is a poor indicator of underlying severity. Mucosal biopsies offer limited value in predicting underlying disease. Ethical animal research: This study was approved by the University of Nottingham Ethics and Welfare Committee. The study was performed on material collected at an abattoir. SOURCE OF FUNDING: None. Competing interests: None declared. PMID- 26374957 TI - The structure of facial spasms. PMID- 26374958 TI - Imported chikungunya fever in Madrid. AB - Chikungunya Fever is a mosquito-transmitted viral disease that causes fever, rash and musculoskeletal complaints. The latest may persist for several months, or even years or developed a relapsing course, that deserve an adequate treatment. Due to the large outbreak declared in the Caribbean in 2013, imported cases of Chikungunya as well as the risk of autochthonous transmission in case of available vectors have increased in non-endemic countries, like Spain. We described four cases of Chikungunya treated in our clinic. PMID- 26374959 TI - Solar energy utilization in the direct photocarboxylation of 2,3-dihydrofuran using CO2. AB - The conversion of CO2 into high energy products (fuels) and the direct carboxylation of C-H bonds require a high energy input. Energy cannot be derived from fossil carbon, in this case. Solar energy can be used instead, with a low environmental impact and good profit. We have studied the use of white light or solar energy in the photoreduction of CO2 and in photocarboxylation reactions, using different semiconductors modified at their surface. Two examples of reduction of CO2 to methanol and CO will be shortly discussed, and two cases of carboxylation of organic substrates. The case of carboxylation of 2,3 dihydrofuran will be discussed in detail. PMID- 26374961 TI - [Not Available]. PMID- 26374960 TI - Gyrification brain abnormalities as predictors of outcome in anorexia nervosa. AB - Gyrification brain abnormalities are considered a marker of early deviations from normal developmental trajectories and a putative predictor of poor outcome in psychiatric disorders. The aim of this study was to explore cortical folding morphology in patients with anorexia nervosa (AN). A MRI brain study was conducted on 38 patients with AN, 20 fully recovered patients, and 38 healthy women. Local gyrification was measured with procedures implemented in FreeSurfer. Vertex-wise comparisons were carried out to compare: (1) AN patients and healthy women; (2) patients with a full remission at a 3-year longitudinal follow-up assessment and patients who did not recover. AN patients exhibited significantly lower gyrification when compared with healthy controls. Patients with a poor 3 year outcome had significantly lower baseline gyrification when compared to both healthy women and patients with full recovery at follow-up, even after controlling for the effects of duration of illness and gray matter volume. No significant correlation has been found between gyrification, body mass index, amount of weight loss, onset age, and duration of illness. Brain gyrification significantly predicted outcome at follow-up even after controlling for the effects of duration of illness and other clinical prognostic factors. Although the role of starvation in determining our findings cannot be excluded, our study showed that brain gyrification might be a predictor of outcome in AN. Further studies are needed to understand if brain gyrification abnormalities are indices of early neurodevelopmental alterations, the consequence of starvation, or the interaction between both factors. PMID- 26374963 TI - [Intraoperative protective ventilation reduces postoperative pulmonary complications - PRO]. AB - Postoperative pulmonary complications add to higher mortality and morbidity. This risk could be lowered with intraoperative protective ventilation, especially with low tidal volumes. The application of PEEP and the use of recruitment maneuvers can enhance the lung function during surgery, but can also cause haemodynamic instability. In patients with open abdominal surgery and no lung damage or obesity, PEEP and recruitment maneuvers have no protective effect against postoperative pulmonary complications. It is still unclear, wether the use of intraoperative PEEP in other patient groups and during different surgery procedures is relevant for lung protection. PMID- 26374964 TI - [Protective ventilation reduces postoperative pulmonary complications - Contra]. AB - Protective ventilation is a treatment strategy for patients with ARDS. The main goals are the prevention of de-recruitment and overinflation and hence development of VILI. Therefore, protective ventilation is an individualised therapy by adjusting PEEP and Vt in respect to patient' own volume-pressure curve. Nowadays the term "protective ventilation" is reduced to ventilation with Vt 6 ml/kg only. Although protective ventilatory strategies are used in patients with severe pulmonary impairment there is a trend to transfer this strategy to healthy humans undergoing surgery. In ventilated patients with healthy lungs a ventilation with Vt higher than 17 ml/kg seems to increase the risk for development of VILI. Nevertheless, many studies show a association between application of protective intraoperative ventilatory strategies and a reduced rate of postoperative pulmonary complications. However, "protective ventilation" has not been standardised yet, and the adequate Vt and PEEP in an individual patient undergoing surgery has still to be clarified. Therefore, due to inconsistent intraoperative ventilation and methodical flaws it remains questionable if a generalized Vt reduction copes this complex topic. One should be aware that reduction of Vt may increase the rate of atelectasis and has been shown to be associated with increased mortality. PMID- 26374965 TI - [Not Available]. PMID- 26374966 TI - [Not Available]. PMID- 26374967 TI - [Perioperative myocardial protection in non-cardiac surgery]. AB - Due to ongoing demographic changes more and more older patients with co-existent cardiac diseases undergo non-cardiac surgery. The risk of postoperative complications, notably myocardial ischemia, is raised in these patients. An accurate preparation before surgery including the risk profile and the management of co-medication is of paramount importance. Beta-blockers and statins should be continued perioperatively. The management of platelet aggregations inhibitors requires an interdisciplinary approach. During surgery, tachycardia as well as hypertension and hypotension should be treated consequently. Perioperative myocardial infarction is often asymptomatic and diagnosis can be difficult. Sufficient analgesia is important in postoperative care of patients with co existing cardiac diseases. PMID- 26374968 TI - [Intraoperative neuroprotection--influence of the anaesthesiological management]. AB - Perioperative neurofunctional disorders may become clinically apparent as e.g. perioperative stroke (POS) or postoperative cognitive deficit (POCD). Newly diagnosed neuro-functional disorders are associated with worsening of postoperative outcome. Focus of this review article is on the possibilities of the intraoperative anaesthesiological management to favourably influence incidence and severity of neurological complications and to improve postoperative outcome. PMID- 26374969 TI - [Nephroprotection--anaesthetic management of renal transplantation]. AB - Kidney transplantation is a standard surgical procedure. Improvements of immunosuppressive therapy, donor management and surgical technique reduced perioperative complications and improved graft survival. In this review the authors discuss the anaesthetic management of kidney transplantation and nephroprotective strategies: reduction of ischemia-reperfusion injury, maintenance of optimal graft perfusion, avoidance of nephrotoxic agents and effective immunosuppression. PMID- 26374970 TI - [Not Available]. PMID- 26374971 TI - [Not Available]. PMID- 26374975 TI - 1,4-Naphthalenediyl-Bridged Molecular Gyrotops: Rotation of the Rotor and Fluorescence in Solution. AB - Macrocage molecules with a bridged pi-electron system have been reported as molecular gyrotops in which the pi-electron system can rotate within the cage. We recently reported the dynamics of the rotor in solution using 1,4-naphthalenediyl bridged molecular gyrotops, which consist of cages formed of three C14, C16, or C18 chains. In this work, we synthesized novel gyrotops with C15 and C17 chains and systematically investigated the activation energies for the rotation of the rotor in solution. The activation energies for rotation in solution were found to decrease with increasing size of the cage. Therefore, a rotational barrier can be designed by adjusting the length of the side chains in these molecular gyrotops. Additionally, these gyrotops were fluorescent in solution; the quantum yields and lifetimes of the fluorescence were investigated. However, these properties were not influenced by the chain length owing to a large difference in time scale between fluorescence (10(-8)-10(-9) s) and the rotational dynamics inside the cage (10 degrees -10(-5) s). PMID- 26374976 TI - Clinical Research Abstracts of the British Equine Veterinary Association Congress 2015. AB - REASONS FOR PERFORMING STUDY: The birthweight of Thoroughbred foals has increased in recent years. It is unknown whether this is associated with increased broodmare obesity or endocrine dysfunction. OBJECTIVES: To determine insulin, leptin and triglyceride concentrations in obese and non-obese Thoroughbred mares throughout gestation and to investigate their association with foal birthweight. STUDY DESIGN: Prospective, cohort study. METHODS: Fifty-seven pregnant Thoroughbred mares were included in the study. From 40 days post-breeding, body condition score (BCS), weight and venous blood samples were obtained every 60 days throughout gestation. Feed was withheld for 6 h before blood sampling. Serum/plasma insulin, leptin and triglyceride concentrations were measured using validated/standard methods. Foal birthweight was recorded. Association of hormone or triglyceride concentration with time, BCS and birthweight were analysed using a linear mixed effects model. A Pearson correlation co-efficient was calculated between hormone or triglyceride concentration, BCS and birthweight. RESULTS: Serum insulin concentrations were significantly greater (P<0.05) at 0-59 days compared with 240-299 days and at 60-119 days compared with 180-359 days gestation. 55% of mares had BCS >= 7. There was 1.5% incidence of fasting hyperinsulinaemia throughout gestation and no association of fasting insulin concentration with BCS. Leptin concentration was significantly (P<0.0001) greater at 180-239 days compared with all other time points and was significantly (r = 0.29, P<0.0003) correlated with BCS. Triglyceride concentration was significantly (P<0.02) greater at 240-299 days compared with earlier time points but was not associated with BCS. Foal birthweight was significantly positively correlated with BCS (r = 0.13, P<0.001) and inversely correlated with leptin concentration at 60-119 days and 240-299 days gestation (r = -0.64, P<0.05). CONCLUSIONS: Mare BCS correlated with foal birthweight such that obese mares had heavier foals. Significant fasting hyperinsulinaemia was not identified in this population. Increased leptin concentration in early and late gestation was associated with decreased foal birthweight and may be useful to predict foal birthweight. Ethical animal research: Informed client consent was obtained for all animals used in the study. SOURCE OF FUNDING: Private donor. Competing interests: None declared. PMID- 26374981 TI - Clinical Research Abstracts of the British Equine Veterinary Association Congress 2015. AB - REASONS FOR PERFORMING STUDY: A quantifiable measure of muscle activity related to the cervical spine may provide further understanding and evidence based support for chiropractic techniques. Surface electromyography (sEMG) is a noninvasive method of measuring muscle activity of the splenius muscle when the horse is at rest. OBJECTIVES: To determine if there is a relationship between objective measurable muscle parameters and misalignments and muscle tension in the equine cervical spine. STUDY DESIGN: Controlled paired randomised study. METHODS: Privately owned horses (n = 14), of mixed sex, age and mean height 157.8 cm were selected and assigned a group by matching work, management regime, age, sex and breed. The treatment group (n = 7) underwent manual chiropractic treatment following palpation. The control group underwent palpation only. A Delsys 4 sensor system was used for data collection. Probes were positioned on the muscle halfway between C1/C2 joint and the crest on the left and right sides, between the tendon insertion and the motor point to maximise signals. sEMG readings were taken at immediately before (0) and after palpation (PP) and 30 min later (30). Data were tested for normality and variance by one-way ANOVA and paired t test. RESULTS: Post treatment, there was a significant decrease (P<0.01) in sEMG activity for treatment group at 0 to 30 and PP to 30. There was a significant decrease (P<0.05) in sEMG for right side for treatment group at 0 to 30 and PP to 30. There were no such significant effects for the control group. The majority (83%) of horses had atlas rotation and tilt to the right. CONCLUSIONS: This preliminary study supports use of sEMG as a means of assessing muscle activity of equines and suggests a statistically significant reduction in splenius muscle activity is observed following manual chiropractic treatment although the benefit to the horse is unknown. Ethical animal research: The study protocol was reviewed by the College Research Ethics Committee before commencement of the study. Owners gave informed consent for their horses' inclusion in the study. SOURCE OF FUNDING: McTimoney College of Chiropractic assisted with the hiring of the equipment. Competing interests: None declared. PMID- 26374982 TI - Clinical Research Abstracts of the British Equine Veterinary Association Congress 2015. AB - REASONS FOR PERFORMING STUDY: Andalusian horses have been proposed as a breed predisposed to equine metabolic syndrome (EMS) phenotype [1] because they are prone to exhibiting regional, generalised adiposity and tendency to laminitis [2]. Insulin dysregulation represents the main pathophysiological cause for all the features of EMS, however there are no epidemiological studies in this breed. OBJECTIVE: To assess insulin dysregulation through insulin proxies in Andalusian horses with different levels of obesity. STUDY DESIGN: Cross-sectional study. METHODS: One hundred and sixty-four Andalusians (78 stallions and 86 mares, 2-15 years) were scored for overall (body condition score, BCS) and neck (cresty neck score, CNS) adiposity. Grain concentrate was withheld for 12 h before sampling. Blood samples were collected between 06.00-10.00 h for basal glucose, insulin concentrations, RISQI and MIRG proxies calculation. Conditions were defined as: obese horses (Ob), BCS >= 7; cresty neck horses (CN), CNS >= 3; hyperinsulinaemia, insulin >=20 MUu/ml; low insulin sensitivity, RISQI<0.32[mu/l](-0.5) and increased insulin secretory response, MIRG>5.6muinsulin (2)/[10.l.mgglucose]. Regarding BCS 2 groups were created: Ob and non-Ob. These groups were subdivided depending on CNS: with CN and without it (nonCN). Ob-nonCN group (n = 2) was excluded for the statistics due to the low number of horses. RESULTS: Of the horses studied, 26.8% were Ob-CN, 42.1% were nonOb-CN and 31.1% were nonOb-nonCN. Ob horses presented higher insulin levels (P = 0.034) and lower RISQI values (P = 0.019) than all nonOb horses. When CN was considered, only RISQI was lower (P = 0.015) in Ob-CN group respect to nonOb nonCN, however nonOb-CN group does not differ from the other 2 groups. Furthermore, the percentage of Ob-CN horses with hyperinsulinaemia (2.3%), abnormal RISQI (4.5%) and MIRG (9.1%) was very low. CONCLUSIONS: These results suggest that in Andalusians, increased adiposity was not clearly associated to insulin dysregulation and, similar to human beings, may coexist as a metabolically healthy but obese phenotype. Ethical animal research: Ethical University Committee approved all the procedures and owner informed consent was obtained. SOURCE OF FUNDING: None. Competing interests: None declared. PMID- 26374983 TI - Exposing evidence is not "fibbing". PMID- 26374984 TI - Selectins in Liver Ischemia and Reperfusion Injury. AB - Liver ischemia reperfusion injury is mediated by a complex system of signaling cascades and inflammatory response resulting in organ damage. Selectins are a group of cell adhesion glycoproteins that play a key role in the initial immunological response. L-selectins, found on leukocytes, initiate the original adhesion and rolling phase of leukocyte extravasation upon liver sinusoidal endothelial cells (LSECs). P-selectins, found on platelets and tissue-specific endothelial cells, further increases leukocyte-endothelial adhesion and rolling. P-selectin-ligand binding also initiates intracellular signals that produce adhesion molecules to start firm adhesion and increase local chemokine production. L-selectin-ligand binding on the leukocytes increases adhesion molecule expression and chemokines, but also initiate changes in intracellular structural actin. E-selectin expression occurs with the presence of TNF-alpha and/or IL-1beta. E-selectin-ligand binding decreases leukocyte rolling velocity and increases adhesion molecules. Together, these glycoproteins transition the leukocyte response from original margination and rolling to firm adhesion and eventually migration. PMID- 26374985 TI - Norepinephrine is required to promote wakefulness and for hypocretin-induced arousal in zebrafish. AB - Pharmacological studies in mammals suggest that norepinephrine (NE) plays an important role in promoting arousal. However, the role of endogenous NE is unclear, with contradicting reports concerning the sleep phenotypes of mice lacking NE due to mutation of dopamine beta-hydroxylase (dbh). To investigate NE function in an alternative vertebrate model, we generated dbh mutant zebrafish. In contrast to mice, these animals exhibit dramatically increased sleep. Surprisingly, despite an increase in sleep, dbh mutant zebrafish have a reduced arousal threshold. These phenotypes are also observed in zebrafish treated with small molecules that inhibit NE signaling, suggesting that they are caused by the lack of NE. Using genetic overexpression of hypocretin (Hcrt) and optogenetic activation of hcrt-expressing neurons, we also find that NE is important for Hcrt induced arousal. These results establish a role for endogenous NE in promoting arousal and indicate that NE is a critical downstream effector of Hcrt neurons. PMID- 26374987 TI - Abstracts from the IVECCS, EVECCS Annual Congresses and ACVECC VetCOT Veterinary Trauma & Critical Care Conference 2015. PMID- 26374988 TI - Aqueous two-phase systems: A simple methodology to obtain mixtures enriched in main toxins of Bothrops alternatus venom. AB - Phospholipase A2 (PLA2) and protease (P) are enzymes responsible of myotoxic, edematogenic and hemostasis disorder effects observed in the envenomation by Bothrops alternatus pitviper. Their partitioning coefficient (Kp) in different polyethyleneglycol/potassium phosphate aqueous two-phase systems (ATPSs) was determined in order to both achieve a better understanding of the partitioning mechanism and define optimal conditions for toxin isolation. Polyethyleneglycols (PEGs) of molecular weights 1000; 3350; 6000 and 8000; different temperatures (5, 20 and 37 degrees C) and phase volume ratios of 0.5; 1 and 2 were assayed. PLA2 partitioned preferentially to the top phase while P mainly distributed to the bottom phase. Either entropically- or enthalpically-driven mechanisms were involved in each case (PLA2 and P). The aqueous two-phase system formed by PEG of MW 3350 (12.20% wt/wt) and KPi pH 7.0 (11.82% wt/wt) with a volume ratio of one and a load of 1.25 mg of venom/g of system showed to be the most efficient to recover both enzymes. It allowed obtaining the 72% of PLA2 in the top phase with a purification factor of 2 and the 82% of P at the bottom phase simultaneously. A further adsorption batch step with DEAE-cellulose was used to remove satisfactorily the PEG from the top phase and recover the active PLA2. The proposed methodology is simple, inexpensive, and only requires professionals trained in handling basic laboratory equipment. It could be easily adoptable by developing countries in which the snakebite accidents cause considerable morbidity and mortality. PMID- 26374986 TI - SPOP mutation leads to genomic instability in prostate cancer. AB - Genomic instability is a fundamental feature of human cancer often resulting from impaired genome maintenance. In prostate cancer, structural genomic rearrangements are a common mechanism driving tumorigenesis. However, somatic alterations predisposing to chromosomal rearrangements in prostate cancer remain largely undefined. Here, we show that SPOP, the most commonly mutated gene in primary prostate cancer modulates DNA double strand break (DSB) repair, and that SPOP mutation is associated with genomic instability. In vivo, SPOP mutation results in a transcriptional response consistent with BRCA1 inactivation resulting in impaired homology-directed repair (HDR) of DSB. Furthermore, we found that SPOP mutation sensitizes to DNA damaging therapeutic agents such as PARP inhibitors. These results implicate SPOP as a novel participant in DSB repair, suggest that SPOP mutation drives prostate tumorigenesis in part through genomic instability, and indicate that mutant SPOP may increase response to DNA damaging therapeutics. PMID- 26374989 TI - Expression and purification of the surface proteins from Andes virus. AB - Andes virus is the main causative agent of Hantavirus cardiopulmonary syndrome in South America. There are currently no vaccines or treatments against Andes virus. However, there are several evidences suggesting that antibodies against Andes virus envelope glycoproteins may be enough to confer full protection against Hantavirus cardiopulmonary syndrome. The goal of the present work was to express, purify and characterize the extracellular domains of Andes virus glycoproteins Gn and Gc. We generated two adenoviral vectors encoding the extracellular domains of Andes virus glycoproteins Gn and Gc. Both molecules were expressed by adenoviral transduction in SiHa cells. We found that sGc ectodomain was mainly secreted into the culture medium, whereas sGn was predominantly retained inside the cells. Both molecules were expressed at very low concentrations (below 1 MUg/mL). Treatment with the proteasome inhibitor ALLN raised sGc concentration in the cell culture medium, but did not affect expression levels of sGn. Both ectodomains were purified by immobilized metal ion affinity chromatography, and were recognized by sera from persons previously exposed to Andes virus. To our knowledge, this is the first work that addresses the expression and purification of Andes virus glycoproteins Gn and Gc. Our results demonstrate that sGn and sGc maintain epitopes that are exposed on the surface of the viral envelope. However, our work also highlights the need to explore new strategies to achieve high-level expression of these proteins for development of a vaccine candidate against Andes virus. PMID- 26374991 TI - Quercetin and hydroxytyrosol attenuates xanthine/xanthine oxidase-induced toxicity in H9c2 cardiomyocytes by regulation of oxidative stress and stress sensitive signaling pathways. AB - The increased activity of xanthine/xanthine oxidase (X/XO) has been suggested as a risk factor for heart disease and herbal polyphenols exhibits cardioprotection in vitro and in vivo. To understand the cardioprotective action mechanisms of polyphenol quercetin and hydroxytyrosol, the expression levels of stress responsive proteins were studied in X/XO-induced toxicity model of H9c2 cardiomyocyocytes. Pretreatment with each polypenol (0.1-10 MUg/ml; 24 h) enhanced viability (p < 0.01; MTT test) and inhibited reactive oxygen species (ROS) generation (p < 0.001; H2DCFDA assay) against 12 h exposure to a free radical generating system, X (0.5 mM) and XO (5 mU/ml). Western blotting experiments showed that X/XO increases the phosphorylation of downstream substrate of p38, MAPK-activated protein kinase 2 (MAPKAPK-2), p44/42-MAPK (Erk1/2) and cleaved caspase-3 (p < 0.001, vs. Control), however inhibits the levels of phosphorylated c-Jun and Hsp27 (p < 0.01, vs. Control). Pretreatment with quercetin or hydroxytyrosol attenuated the phosphorylation of MAPKAPK-2 and cleaved caspase-3 in X/XO-exposed cells (p < 0.01, vs. X/XO). Hydroxytyrosol enhanced the reduction of phosphorylation of a transcriptional target c-Jun and led to overphosphorylation in protective proteins, p44/42-MAPK and Hsp27 in X/XO exposed cells (p < 0.01, vs. X/XO). Our data suggest that quercetin and hydroxytyrosol protects cardiomyocytes against X/XO-induced oxidative toxicity by diminishing intracellular ROS and the regulation of stress-sensitive protein kinase cascades and transcription factors. PMID- 26374990 TI - Gender and nonmedical prescription opioid use and DSM-5 nonmedical prescription opioid use disorder: Results from the National Epidemiologic Survey on Alcohol and Related Conditions - III. AB - BACKGROUND: Little is known about sex-specific risk for nonmedical prescription opioid use (NMPOU) and DSM-5 nonmedical prescription opioid use disorder (NMPOUD). The objective of the present study was to present prevalence, correlates, psychiatric comorbidity, treatment and disability of NMPOU and DSM-5 NMPOUD among men and women. METHODS: Nationally representative sample of the U.S. RESULTS: Prevalences of 12-month and lifetime NMPOU were greater among men (4.4%, 13.0%) than women (3.9%, 9.8%), while corresponding rates of DSM-5 NMPOUD did not differ between men (0.9%, 2.2%) and women (0.9%, 1.9%). Regardless of time frame and sex, NMPOU and NMPOUD generally decreased with age and were lower among Blacks, Asians/Pacific Islanders and Hispanics, and respondents with lower socioeconomic status. Among men with NMPOU, rates were lower among respondents in the Northeast and South and among those previously married (lifetime). Across time frames and gender, NMPOU and NMPOUD were generally associated with other substance use disorders, posttraumatic stress and borderline, schizotypal and antisocial personality disorders, but associated with major depressive disorder, persistent depression and bipolar I disorder only among men. Disability increased with NMPOU frequency and NMPOUD severity. Only 7.6% and 8.2% of men and women with NMPOU ever received treatment, while 26.8% and 31.1% ever received treatment for NMPOUD. CONCLUSIONS: NMPOU and NMPOUD are highly disabling, associated with a broad array of sex-specific and shared correlates and comorbidities and largely go untreated in the U.S. Valid assessment tools are needed that include gender as a stratification variable to identify NMPOU and NMPOUD. PMID- 26374992 TI - Pleiotropic protective roles of melatonin against aluminium-induced toxicity in rats. AB - This study aimed to investigate the potential effects of melatonin on aluminium induced toxicity in a rat model using a set of biochemical, inflammatory, oxidant, lipid profile criteria and hepatic integrity (verified by hematoxylin eosin staining). The results indicated that AlCl3 administration during 60 days (100 mg/kg b.w.) significantly increased the activities of transaminases AST and ALT by 46% (p < 0.001) and 21% (p < 0.01), lactate dehydrogenase (LDH) by 30% (p < 0.001), the levels of bilirubin by 85% (p < 0.001), total cholesterol by 115% (p < 0.001), triglycerides by 130% (p < 0.001), LDL-cholesterol by 413% (p < 0.001), oxidized LDL (oxLDL) by 51% (p < 0.01) and apolipoprotein B100 (apoB100) by 63% (p < 0.001), as compared to controls. The inflammatory markers (TNF-alpha, IL-2, and IL-6) were significantly increased (p < 0.001), associated to higher lipid peroxidation (TBARS) level. Also, both plasma HDL-cholesterol level and hepatic LDL receptors (p < 0.01) expression and antioxidant protein (SOD, CAT, and GPx) activities are decreased. Those physiological disturbances were, however, noted to alleviate following the co-administration of melatonin (10 mg/kg b.w.). Overall, the present study is the first to provide evidence on the anti-inflammatory, anti-oxidant, anti-lipidic and, hence, therapeutic effects of melatonin with regard to the control and prevention of aluminium-intoxication. PMID- 26374993 TI - The effects of endocannabinoid receptor agonist anandamide and antagonist rimonabant on opioid analgesia and tolerance in rats. AB - The role of the cannabinoid (CB) system in the tolerance to analgesic effect of opioid remains obscure. The aim of the present study was to evaluate the effects of the endocannabinoid nonselective receptor agonist anandamide (AEA) and CB1 receptor antagonist rimonabant (SR141716) on morphine analgesia and tolerance in rats. Male Wistar albino rats weighing 215-230 g were used in these experiments. To constitute morphine analgesic tolerance, a 3-day cumulative dosing regimen was used. The analgesic effects of AEA (10 mg/kg), SR141716 (10 mg/kg), and morphine (5 mg/kg) were considered at 30-min intervals by tail flick (TF) and hot plate (HP) analgesia tests. The analgesic effects of the drugs were measured as TF and HP latencies in all groups for each rat and converted to %MPE. The data were analysed by analysis of variance followed by Tukey test. The findings suggested that AEA in combination with morphine produced a significant increase in expression of analgesic tolerance to morphine. Conversely, cannabinoid receptor antagonist SR141716 attenuated morphine analgesic tolerance. In addition, administration of AEA with morphine increased morphine analgesia. In conclusion, we observed that the cannabinoid receptor agonist anandamide and CB1 receptor antagonist SR141716 plays a significant role in the opioid analgesia and tolerance. PMID- 26374994 TI - Synergism between phorbol myristate acetate and calcium ionophore in inducing proliferation of in vitro gamma-irradiated murine lymphocytes. AB - The objective of this study was to analyze the in vitro effects of gamma irradiation (0-5 Gy) on lymphocyte proliferation in animals sensitive to radiation as BALB/c mice. Lymphocytes were irradiated and underwent different treatments: quiescent cells were cultured with calcium ionophore A23187 (5 min or 48 h) with or without phorbol myristate acetate (PMA); lymphocytes (control cells or incubated with A23187 and PMA) were also cultured with four mitogens that are specific to the different subpopulations to determine the degree of inhibition of the response to radiation. Results obtained indicated that in quiescent cells, A23187 and PMA treatment had a mitogenic effect, which peaked with long A23187 treatment (48 h); synergism was further demonstrated between both drugs and was enhanced with higher ionizing radiation doses. However, in both irradiated and non-irradiated mitogen-stimulated cells, A23187 (48 h) and PMA had a strong inhibitory effect on cell proliferation. In conclusion these results indicate that irradiated BALB/c mice lymphocytes respond to treatment with A23187 and PMA more actively than controls. Inhibition of the post-exposure mitogen-induced proliferative response and the synergic effect between A23187 and PMA also suggest altered PKC activation mechanisms in cell membranes. Comparing with previous studies with in vivo irradiated mice, the effects of IR in vitro were less intense. PMID- 26374995 TI - Rosmarinic acid mitigates signs of systemic oxidative stress in streptozotocin induced diabetes in rats. AB - The aim of the work was to study the effect of rosmarinic acid (RA) on markers of oxidative stress in rats with diabetes. Diabetes was induced by streptozotocin (STZ), RA was administered orally for ten weeks. Water consumption was measured daily. Ten weeks after the first RA administration, urine was collected over 15 hours. N-acetyl-beta-D-glucosaminidase (NAGA) activity, levels of thiobarbituric acid reactive substances (TBARS) and glutathione (GSH) were determined in the pancreas, kidney, and plasma. RA administration to diabetic rats ameliorated markers of oxidative stress, as well as water consumption and urination. We assume that RA may mitigate STZ-induced diabetic manifestations by protecting rat tissues against damaging effect of free radicals. PMID- 26374996 TI - Overexpressing superoxide dismutase 2 induces a supernormal cardiac function by enhancing redox-dependent mitochondrial function and metabolic dilation. AB - During heightened cardiac work, O2 consumption by the heart benefits energy production via mitochondria. However, some electrons leak from the respiratory chain and yield superoxide, which is rapidly metabolized into H2O2 by SOD2. To understand the systemic effects of the metabolic dilator, H2O2, we studied mice with cardiac-specific SOD2 overexpression (SOD2-tg), which increases the H2O2 produced by cardiac mitochondria. Contrast echocardiography was employed to evaluate cardiac function, indicating that SOD2-tg had a significantly greater ejection fraction and a lower mean arterial pressure (MAP) that was partially normalized by intravenous injection of catalase. Norepinephrine-mediated myocardial blood flow (MBF) was significantly enhanced in SOD2-tg mice. Coupling of MBF to the double product (Heart Rate*MAP) was increased in SOD2-tg mice, indicating that the metabolic dilator, "spilled" over, inducing systemic vasodilation. The hypothesis that SOD2 overexpression effectively enhances mitochondrial function was further evaluated. Mitochondria of SOD2-tg mice had a decreased state 3 oxygen consumption rate, but maintained the same ATP production flux under the basal and L-NAME treatment conditions, indicating a higher bioenergetic efficiency. SOD2-tg mitochondria produced less superoxide, and had lower redox activity in converting cyclic hydroxylamine to stable nitroxide, and a lower GSSG concentration. EPR analysis of the isolated mitochondria showed a significant decrease in semiquinones at the SOD2-tg Qi site. These results support a more reductive physiological setting in the SOD2-tg murine heart. Cardiac mitochondria exhibited no significant differences in the respiratory control index between WT and SOD2-tg. We conclude that SOD2 overexpression in myocytes enhances mitochondrial function and metabolic vasodilation, leading to a phenotype of supernormal cardiac function. PMID- 26374998 TI - Novel competitors shape species' responses to climate change. AB - Understanding how species respond to climate change is critical for forecasting the future dynamics and distribution of pests, diseases and biological diversity. Although ecologists have long acknowledged species' direct physiological and demographic responses to climate, more recent work suggests that these direct responses can be overwhelmed by indirect effects mediated via other interacting community members. Theory suggests that some of the most dramatic impacts of community change will probably arise through the assembly of novel species combinations after asynchronous migrations with climate. Empirical tests of this prediction are rare, as existing work focuses on the effects of changing interactions between competitors that co-occur today. To explore how species' responses to climate warming depend on how their competitors migrate to track climate, we transplanted alpine plant species and intact plant communities along a climate gradient in the Swiss Alps. Here we show that when alpine plants were transplanted to warmer climates to simulate a migration failure, their performance was strongly reduced by novel competitors that could migrate upwards from lower elevation; these effects generally exceeded the impact of warming on competition with current competitors. In contrast, when we grew the focal plants under their current climate to simulate climate tracking, a shift in the competitive environment to novel high-elevation competitors had little to no effect. This asymmetry in the importance of changing competitor identity at the leading versus trailing range edges is best explained by the degree of functional similarity between current and novel competitors. We conclude that accounting for novel competitive interactions may be essential to predict species' responses to climate change accurately. PMID- 26374997 TI - Nanoparticle biointerfacing by platelet membrane cloaking. AB - Development of functional nanoparticles can be encumbered by unanticipated material properties and biological events, which can affect nanoparticle effectiveness in complex, physiologically relevant systems. Despite the advances in bottom-up nanoengineering and surface chemistry, reductionist functionalization approaches remain inadequate in replicating the complex interfaces present in nature and cannot avoid exposure of foreign materials. Here we report on the preparation of polymeric nanoparticles enclosed in the plasma membrane of human platelets, which are a unique population of cellular fragments that adhere to a variety of disease-relevant substrates. The resulting nanoparticles possess a right-side-out unilamellar membrane coating functionalized with immunomodulatory and adhesion antigens associated with platelets. Compared to uncoated particles, the platelet membrane-cloaked nanoparticles have reduced cellular uptake by macrophage-like cells and lack particle-induced complement activation in autologous human plasma. The cloaked nanoparticles also display platelet-mimicking properties such as selective adhesion to damaged human and rodent vasculatures as well as enhanced binding to platelet-adhering pathogens. In an experimental rat model of coronary restenosis and a mouse model of systemic bacterial infection, docetaxel and vancomycin, respectively, show enhanced therapeutic efficacy when delivered by the platelet mimetic nanoparticles. The multifaceted biointerfacing enabled by the platelet membrane cloaking method provides a new approach in developing functional nanoparticles for disease-targeted delivery. PMID- 26374999 TI - Neutrophil ageing is regulated by the microbiome. AB - Blood polymorphonuclear neutrophils provide immune protection against pathogens, but may also promote tissue injury in inflammatory diseases. Although neutrophils are generally considered to be a relatively homogeneous population, evidence for heterogeneity is emerging. Under steady-state conditions, neutrophil heterogeneity may arise from ageing and replenishment by newly released neutrophils from the bone marrow. Aged neutrophils upregulate CXCR4, a receptor allowing their clearance in the bone marrow, with feedback inhibition of neutrophil production via the IL-17/G-CSF axis, and rhythmic modulation of the haematopoietic stem-cell niche. The aged subset also expresses low levels of L selectin. Previous studies have suggested that in vitro-aged neutrophils exhibit impaired migration and reduced pro-inflammatory properties. Here, using in vivo ageing analyses in mice, we show that neutrophil pro-inflammatory activity correlates positively with their ageing whilst in circulation. Aged neutrophils represent an overly active subset exhibiting enhanced alphaMbeta2 integrin activation and neutrophil extracellular trap formation under inflammatory conditions. Neutrophil ageing is driven by the microbiota via Toll-like receptor and myeloid differentiation factor 88-mediated signalling pathways. Depletion of the microbiota significantly reduces the number of circulating aged neutrophils and dramatically improves the pathogenesis and inflammation-related organ damage in models of sickle-cell disease or endotoxin-induced septic shock. These results identify a role for the microbiota in regulating a disease-promoting neutrophil subset. PMID- 26375000 TI - Immunology: Caspase target drives pyroptosis. PMID- 26375001 TI - Erratum: Evidence for human transmission of amyloid-beta pathology and cerebral amyloid angiopathy. PMID- 26375002 TI - Corrigendum: Selective killing of cancer cells by a small molecule targeting the stress response to ROS. PMID- 26375003 TI - Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death. AB - Inflammatory caspases (caspase-1, -4, -5 and -11) are critical for innate defences. Caspase-1 is activated by ligands of various canonical inflammasomes, and caspase-4, -5 and -11 directly recognize bacterial lipopolysaccharide, both of which trigger pyroptosis. Despite the crucial role in immunity and endotoxic shock, the mechanism for pyroptosis induction by inflammatory caspases is unknown. Here we identify gasdermin D (Gsdmd) by genome-wide clustered regularly interspaced palindromic repeat (CRISPR)-Cas9 nuclease screens of caspase-11- and caspase-1-mediated pyroptosis in mouse bone marrow macrophages. GSDMD-deficient cells resisted the induction of pyroptosis by cytosolic lipopolysaccharide and known canonical inflammasome ligands. Interleukin-1beta release was also diminished in Gsdmd(-/-) cells, despite intact processing by caspase-1. Caspase-1 and caspase-4/5/11 specifically cleaved the linker between the amino-terminal gasdermin-N and carboxy-terminal gasdermin-C domains in GSDMD, which was required and sufficient for pyroptosis. The cleavage released the intramolecular inhibition on the gasdermin-N domain that showed intrinsic pyroptosis-inducing activity. Other gasdermin family members were not cleaved by inflammatory caspases but shared the autoinhibition; gain-of-function mutations in Gsdma3 that cause alopecia and skin defects disrupted the autoinhibition, allowing its gasdermin-N domain to trigger pyroptosis. These findings offer insight into inflammasome-mediated immunity/diseases and also change our understanding of pyroptosis and programmed necrosis. PMID- 26375004 TI - A sexually dimorphic hypothalamic circuit controls maternal care and oxytocin secretion. AB - It is commonly assumed, but has rarely been demonstrated, that sex differences in behaviour arise from sexual dimorphism in the underlying neural circuits. Parental care is a complex stereotypic behaviour towards offspring that is shared by numerous species. Mice display profound sex differences in offspring-directed behaviours. At their first encounter, virgin females behave maternally towards alien pups while males will usually ignore the pups or attack them. Here we show that tyrosine hydroxylase (TH)-expressing neurons in the anteroventral periventricular nucleus (AVPV) of the mouse hypothalamus are more numerous in mothers than in virgin females and males, and govern parental behaviours in a sex specific manner. In females, ablating the AVPV TH(+) neurons impairs maternal behaviour whereas optogenetic stimulation or increased TH expression in these cells enhance maternal care. In males, however, this same neuronal cluster has no effect on parental care but rather suppresses inter-male aggression. Furthermore, optogenetic activation or increased TH expression in the AVPV TH(+) neurons of female mice increases circulating oxytocin, whereas their ablation reduces oxytocin levels. Finally, we show that AVPV TH(+) neurons relay a monosynaptic input to oxytocin-expressing neurons in the paraventricular nucleus. Our findings uncover a previously unknown role for this neuronal population in the control of maternal care and oxytocin secretion, and provide evidence for a causal relationship between sexual dimorphism in the adult brain and sex differences in parental behaviour. PMID- 26375005 TI - Epicardial FSTL1 reconstitution regenerates the adult mammalian heart. AB - The elucidation of factors that activate the regeneration of the adult mammalian heart is of major scientific and therapeutic importance. Here we found that epicardial cells contain a potent cardiogenic activity identified as follistatin like 1 (Fstl1). Epicardial Fstl1 declines following myocardial infarction and is replaced by myocardial expression. Myocardial Fstl1 does not promote regeneration, either basally or upon transgenic overexpression. Application of the human Fstl1 protein (FSTL1) via an epicardial patch stimulates cell cycle entry and division of pre-existing cardiomyocytes, improving cardiac function and survival in mouse and swine models of myocardial infarction. The data suggest that the loss of epicardial FSTL1 is a maladaptive response to injury, and that its restoration would be an effective way to reverse myocardial death and remodelling following myocardial infarction in humans. PMID- 26375006 TI - BCL11A enhancer dissection by Cas9-mediated in situ saturating mutagenesis. AB - Enhancers, critical determinants of cellular identity, are commonly recognized by correlative chromatin marks and gain-of-function potential, although only loss-of function studies can demonstrate their requirement in the native genomic context. Previously, we identified an erythroid enhancer of human BCL11A, subject to common genetic variation associated with the fetal haemoglobin level, the mouse orthologue of which is necessary for erythroid BCL11A expression. Here we develop pooled clustered regularly interspaced palindromic repeat (CRISPR)-Cas9 guide RNA libraries to perform in situ saturating mutagenesis of the human and mouse enhancers. This approach reveals critical minimal features and discrete vulnerabilities of these enhancers. Despite conserved function of the composite enhancers, their architecture diverges. The crucial human sequences appear to be primate-specific. Through editing of primary human progenitors and mouse transgenesis, we validate the BCL11A erythroid enhancer as a target for fetal haemoglobin reinduction. The detailed enhancer map will inform therapeutic genome editing, and the screening approach described here is generally applicable to functional interrogation of non-coding genomic elements. PMID- 26375007 TI - Cardiac biology: A protein for healing infarcted hearts. PMID- 26375008 TI - The effect of malaria control on Plasmodium falciparum in Africa between 2000 and 2015. AB - Since the year 2000, a concerted campaign against malaria has led to unprecedented levels of intervention coverage across sub-Saharan Africa. Understanding the effect of this control effort is vital to inform future control planning. However, the effect of malaria interventions across the varied epidemiological settings of Africa remains poorly understood owing to the absence of reliable surveillance data and the simplistic approaches underlying current disease estimates. Here we link a large database of malaria field surveys with detailed reconstructions of changing intervention coverage to directly evaluate trends from 2000 to 2015, and quantify the attributable effect of malaria disease control efforts. We found that Plasmodium falciparum infection prevalence in endemic Africa halved and the incidence of clinical disease fell by 40% between 2000 and 2015. We estimate that interventions have averted 663 (542-753 credible interval) million clinical cases since 2000. Insecticide-treated nets, the most widespread intervention, were by far the largest contributor (68% of cases averted). Although still below target levels, current malaria interventions have substantially reduced malaria disease incidence across the continent. Increasing access to these interventions, and maintaining their effectiveness in the face of insecticide and drug resistance, should form a cornerstone of post-2015 control strategies. PMID- 26375009 TI - Single cell activity reveals direct electron transfer in methanotrophic consortia. AB - Multicellular assemblages of microorganisms are ubiquitous in nature, and the proximity afforded by aggregation is thought to permit intercellular metabolic coupling that can accommodate otherwise unfavourable reactions. Consortia of methane-oxidizing archaea and sulphate-reducing bacteria are a well-known environmental example of microbial co-aggregation; however, the coupling mechanisms between these paired organisms is not well understood, despite the attention given them because of the global significance of anaerobic methane oxidation. Here we examined the influence of interspecies spatial positioning as it relates to biosynthetic activity within structurally diverse uncultured methane-oxidizing consortia by measuring stable isotope incorporation for individual archaeal and bacterial cells to constrain their potential metabolic interactions. In contrast to conventional models of syntrophy based on the passage of molecular intermediates, cellular activities were found to be independent of both species intermixing and distance between syntrophic partners within consortia. A generalized model of electric conductivity between co associated archaea and bacteria best fit the empirical data. Combined with the detection of large multi-haem cytochromes in the genomes of methanotrophic archaea and the demonstration of redox-dependent staining of the matrix between cells in consortia, these results provide evidence for syntrophic coupling through direct electron transfer. PMID- 26375010 TI - A concise synthesis of (+)-batzelladine B from simple pyrrole-based starting materials. AB - Alkaloids, secondary metabolites that contain basic nitrogen atoms, are some of the most well-known biologically active natural products in chemistry and medicine. Although efficient laboratory synthesis of alkaloids would enable the study and optimization of their biological properties, their preparation is often complicated by the basicity and nucleophilicity of nitrogen, its susceptibility to oxidation, and its ability to alter reaction outcomes in unexpected ways--for example, through stereochemical instability and neighbouring group participation. Efforts to address these issues have led to the invention of a large number of protecting groups that temper the reactivity of nitrogen; however, the use of protecting groups typically introduces additional steps and obstacles into the synthetic route. Alternatively, the use of aromatic nitrogen heterocycles as synthetic precursors can attenuate the reactivity of nitrogen and streamline synthetic strategies. Here we use such an approach to achieve a synthesis of the complex anti-HIV alkaloid (+)-batzelladine B in nine steps (longest linear sequence) from simple pyrrole-based starting materials. The route uses several key transformations that would be challenging or impossible to implement using saturated nitrogen heterocycles and highlights some of the advantages of beginning with aromatic reagents. PMID- 26375011 TI - Nanotechnology: Platelet mimicry. PMID- 26375013 TI - The effect of phosphorylation on arrestin-rhodopsin interaction in the squid visual system. AB - Invertebrate visual opsins are G protein-coupled receptors coupled to retinoid chromophores that isomerize reversibly between inactive rhodopsin and active metarhodopsin upon absorption of photons of light. The squid visual system has an arrestin protein that binds to metarhodopsin to block signaling to Gq and activation of phospholipase C. Squid rhodopsin kinase (SQRK) can phosphorylate both metarhodopsin and arrestin, a dual role that is unique among the G protein coupled receptor kinases. The sites and role of arrestin phosphorylation by SQRK were investigated here using recombinant proteins. Arrestin was phosphorylated on serine 392 and serine 397 in the C-terminus. Unphosphorylated arrestin bound to metarhodopsin and phosphorylated metarhodopsin with similar high affinities (Kd 33 and 21 nM respectively), while phosphorylation of arrestin reduced the affinity 3- to 5-fold (Kd 104 nM). Phosphorylation of metarhodopsin slightly increased the dissociation of arrestin observed during a 1 hour incubation. Together these studies suggest a unique role for SQRK in phosphorylating both receptor and arrestin and inhibiting the binding of these two proteins in the squid visual system. Invertebrate visual systems are inactivated by arrestin binding to metarhodopsin that does not require receptor phosphorylation. Here we show that squid rhodopsin kinase phosphorylates arrestin on two serines (S392,S397) in the C-terminus and phosphorylation decreases the affinity of arrestin for squid metarhodopsin. Metarhodopsin phosphorylation has very little effect on arrestin binding but does increase arrestin dissociation. PMID- 26375012 TI - Preclinical Evidence for the Use of Sunitinib Malate in the Treatment of Plexiform Neurofibromas. AB - PURPOSE: Plexiform neurofibromas (pNF) are pathognomonic nerve and soft tissue tumors of neurofibromatosis type I (NF1), which are highly resistant to conventional chemotherapy and associated with significant morbidity/mortality. Disruption of aberrant SCF/c-Kit signaling emanating from the pNF microenvironment induced the first ever objective therapeutic responses in a recent phase 2 trial. Sunitinib malate is a potent, highly selective RTK inhibitor with activity against c-Kit, PDGFR, and VEGFR, which have also been implicated in the pathogenesis of these lesions. Here, we evaluate the efficacy of sunitinib malate in a preclinical Krox20;Nf1(flox/-) pNF murine model. EXPERIMENTAL DESIGN: Proliferation, beta-hexosaminidase release (degranulation), and Erk1/2 phosphorylation were assessed in sunitinib treated Nf1(+/-) mast cells and fibroblasts, respectively. Krox20;Nf1(flox/-) mice with established pNF were treated sunitinib or PBS-vehicle control for a duration of 12 weeks. pNF metabolic activity was monitored by serial [(18)F]DG-PET/CT imaging. RESULTS: Sunitinib suppressed multiple in vitro gain-in-functions of Nf1(+/-) mast cells and fibroblasts and attenuated Erk1/2 phosphorylation. Sunitinib treated Krox20;Nf1(flox/-) mice exhibited significant reductions in pNF size, tumor number, and FDG uptake compared to control mice. Histopathology revealed reduced tumor cellularity and infiltrating mast cells, markedly diminished collagen deposition, and increased cellular apoptosis in sunitinib treated pNF. CONCLUSIONS: Collectively, these results demonstrate the efficacy of sunitinib in reducing tumor burden in Krox20;Nf1(flox/-) mice. These preclinical findings demonstrate the utility of inhibiting multiple RTKs in pNF and provide insights into the design of future clinical trials. PMID- 26375014 TI - Performance of chemically modified plastic blood collection tubes. AB - OBJECTIVE: The objective of this study was to compare newly-modified and aged chemoPET tubes, which contain no problematic surfactants, with commercially available serum blood collection tubes (BCTs) for use in analysis of cortisol, total triiodothyronine (TT3), total thyroxine (TT4), and routine clinical chemistry analytes in serum from apparently healthy volunteers and pooled quality control (QC) specimens. MATERIALS AND METHODS: Blood specimens collected from 60 apparently healthy volunteers (18 males, 42 females) and pooled QC specimens poured into seven different BCTs were analyzed by a trained phlebotomist. Cortisol, TT3, and TT4 levels were measured on an Immulite 1000 instrument and routine chemistry tests were analyzed on a Siemens RxL instrument. The significance of differences between chemoPET and other BCT types compared to glass tubes were assessed by Student's paired t-test or repeated measures ANOVA or their non-parametric equivalents. The BCT-related biases (deviation from glass tubes) in analyte concentrations were compared with the current desirable allowable bias, derived from biological variation. Serum analyte concentrations in the different BCTs that exceeded their respective significant change limits were considered clinically significant. RESULTS: No statistically and/or clinically significant differences were noted in the analyte concentrations from serum specimens and pooled QC material when our newly modified and aged chemoPET tubes were compared to glass and other BCTs. CONCLUSIONS: The chemoPET tubes described here may be a suitable alternative to serum BCTs that contain problematic surfactants known to interfere with some clinical assays on the Immulite 1000 and RxL instruments. PMID- 26375015 TI - Clinical Research Abstracts of the British Equine Veterinary Association Congress 2015. AB - REASONS FOR PERFORMING STUDY: Colic is the most common equine emergency problem, and one of the main causes of equid deaths. The horse owners' ability to recognise colic is a critical first step in determining case outcome. OBJECTIVES: To assess equine owners' knowledge and recognition of colic. STUDY DESIGN: Online questionnaire of horse owners. METHODS: An online survey was designed to evaluate owners' approach to colic in the horse. The survey included questions on owner demographics, their recognition of colic (including owner's opinions of their ability to recognise colic, their approach, and their recognition of colic using case vignettes), and their knowledge of normal ranges for clinical parameters. Descriptive and chi squared statistical analysis was performed. RESULTS: The survey was completed by 1061 UK respondents. Six per cent of owners thought they could recognise all types of colic, 61% said they could recognise most cases and 30% said they could recognise some but not all cases. Owners said they would assess faecal output (73% of respondents), gastrointestinal sounds (69%), respiratory rate (62%) and heart rate (50%) in horses with suspected colic. One fifth (22%) of owners would call a vet immediately without assessing any parameters. Many respondents either did not know, or provided incorrect estimates of normal values for clinical parameters: 30.4% were 'unsure' of the normal heart rate and 35.5% gave heart rate values which were outside reference ranges; only 24.5% gave appropriate values for normal respiratory rates and only 31% gave normal temperature values. There was no statistical significance between participants' age, educational qualifications, or their experience with horses and their knowledge of normal clinical parameters. CONCLUSIONS: Owners varied in their approach and ability to recognise colic, and many had significant gaps in their knowledge of normal parameters. Educational materials and/or training to assist owners could help address these issues. Ethical animal research: The study did not involve animal research. The study was reviewed and approved by the Ethics Committee, School of Veterinary Medicine and Science, University of Nottingham. The questionnaire was conducted in accordance with the 1998 Data Protection Act, and the British Educational Research Association's Revised Ethical Guidelines for Educational Research (2004). SOURCE OF FUNDING: Adelle Bowden's studentship is funded by the School of Veterinary Medicine and Science, University of Nottingham. Competing interests: None declared. PMID- 26375016 TI - Environmental changes during the last millennium based on multi-proxy palaeoecological records in a savanna-forest mosaic from the northernmost Brazilian Amazon region. AB - The environmental changes and the dynamics of the savanna-forest mosaic, over the last 1050 years, have been reconstructed by pollen, charcoal, radiocarbon dating mineralogical and geochemical analyses of sediment cores taken from three different Mauritia flexuosapalm swamps in the northernmost part of the Brazilian Amazon region (northern state of Roraima). Studies on the relationship between the modern pollen rain and the regional vegetation provide additional information for the interpretation of the fossil pollen records. The fossil pollen assemblages and geochemical results indicate relatively wet climatic conditions throughout the recorded period. Despite these moist conditions, fires were frequent and are one of the reasons for the dominance of a grassy savanna instead of forest expansion in the study area. Considering the generally wet climatic conditions, these fires were most likely caused by human activities. Even today, fires hinder forest expansion into savanna areas. Sandy hydromorphic soils may also act as an edaphic control to maintain the current sharp boundary between forest and savanna ecosystems. PMID- 26375017 TI - Counteracting effects on free radicals and histological alterations induced by a fraction with casearins. AB - Casearia sylvestris Swartz is a medicinal plant widely distributed in Brazil. It has anti-inflammatory, antiulcer and antitumor activities and is popularly used to treat snakebites, wounds, diarrhea, flu and chest colds. Its leaves are rich in oxygenated tricyclic cis-clerodane diterpenes, particulary casearins. Herein, we evaluated the antioxidant activities of a fraction with casearins (FC) isolated from C. sylvestris and histological changes on the central nervous system and livers of Mus musculus mice. Firstly, in vitro studies (0.9, 1.8, 3.6, 5.4 and 7.2 MUg/mL) revealed EC50 values of 3.7, 6.4 and 0.16 ug/mL for nitrite, hydroxyl radical and TBARS levels, respectively. Secondly, FC (2.5, 5, 10 and 25 mg/kg/day) was intraperitoneally administered to Swiss mice for 7 consecutive days. Nitrite levels in the hippocampus (26.2, 27.3, 30.2 and 26.6 uM) and striatum (26.3, 25.4, 34.3 and 27.5 uM) increased in all treated animals (P < 0.05). Lower doses dropped reduced glutathione, catalase and TBARS levels in the hippocampus and striatum. With the exception of this reduction in TBARS formation, FC displayed only in vitro antioxidant activity. Animals exhibited histological alterations suggestive of neurotoxicity and hepatotoxicity, indicating the need for precaution regarding the consumption of medicinal formulations based on Casearia sylvestris. PMID- 26375018 TI - Ground level photosynthetically active radiation dynamics in stands of Acacia mearnsii De Wild. AB - The objective is to study the dynamics of photosynthetic radiation reaching the soil surface in stands of Acacia mearnsii De Wild and its influence on height growth in stands. This fact gives rise to the formulation of the following hypothesis for this study: "The reduction of the incidence of light inside the stand of black wattle will cause the inflection point in its height growth when this reaches 4 to 5 m in height, i.e. when the stand is between 2 and 3 years of age". The study was conducted in stands in the state of Rio Grande do Sul, Brazil, where diameters at breast height, total height and photosynthetically active radiation available at ground level were measured. The frequency tended to be more intense when the age of the stands increases. It was evident that a reduction of light incidence inside the forest occurred, caused by canopy closure. Consequently, closed canopy propitiated the competition of plants. This has affected the conditions for growth in diameter and height of this species, reason why it becomes possible to conceive the occurrence of an inflection point in the growth of these two variables, confirming the formulated hypothesis. PMID- 26375019 TI - Physicochemical, in vitro and in vivo evaluation of flurbiprofen microemulsion. AB - Flurbiprofen, a potent nonsteroidal anti-inflammatory drug, is widely used for relief of pain in patients suffering from rheumatic diseases, migraine, sore throat and primary dysmenorrheal. However, this drug has many gastrointestinal side effects produced by its oral administration, such as gastric bleeding and peptic ulcer. These effects were responsible for non-compliance among patients, which ultimately results in treatment failure. The physicochemical properties of flurbiprofen, make it a suitable candidate for transdermal drug delivery, which can overcome the drawbacks of oral administration. In this sense, microemulsions have been proved to increase the cutaneous absorption of lipophilic drugs when compared to conventional drug delivery systems. The purpose of this study was to formulate and characterize gel based microemulsions, for topical delivery of flurbiprofen. Different gel bases, containing microemulsion and hydro-alcoholic solution of flurbiprofen, were developed and compared. In vitro study showed that gels containing microemulsion had a higher permeation rate than those containing hydro-alcoholic solutions. Additionally, formulation of Carbopol-I (microemulsion) showed higher percent of inhibition of inflammation than others bases. Further, skin irritation study demonstrated that Carbopol-I was none irritating. Flurbiprofen microemulsion incorporated on Carbopol-I showed physicochemical, in vitro and in vivo characteristics suitable for the development of alternative transdermal delivery formulation. PMID- 26375020 TI - Bacterial and Archaeal Communities Variability Associated with Upwelling and Anthropogenic Pressures in the Protection Area of Arraial do Cabo (Cabo Frio region - RJ). AB - Upwelling systems contain a high diversity of pelagic microorganisms and their composition and activity are defined by factors like temperature and nutrient concentration. Denaturing gradient gel electrophoresis (DGGE) technique was used to verify the spatial and temporal genetic variability of Bacteria and Archaea in two stations of the Arraial do Cabo coastal region, one under upwelling pressure and another under anthropogenic pressure. In addition, biotic and abiotic variables were measured in surface and deep waters from three other stations between these stations. Six samplings were done during a year and adequately represented the degrees of upwelling and anthropogenic pressures to the system. Principal Component Analysis (PCA) showed negative correlations between the concentrations of ammonia and phosphorous with prokaryotic secondary production and the total heterotrophic bacteria. PCA also showed negative correlation between temperature and the abundance of prokaryotic cells. Bacterial and archaeal compositions were changeable as were the oceanographic conditions, and upwelling had a regional pressure while anthropogenic pressure was punctual. We suggest that the measurement of prokaryotic secondary production was associated with both Bacteria and Archaea activities, and that substrate availability and temperature determine nutrients cycling. PMID- 26375021 TI - Prevalence of Candida tropicalis and Candida krusei in onychomycosis in Joao Pessoa, Paraiba, Brazil from 1999 to 2010. AB - Over time, as the etiology of onychomycosis has developed, yeasts from the genus Candida have emerged as important etiological agents. This study aimed to determine the frequency of yeast caused onychomycosis in Joao Pessoa, Paraiba, Brazil from 1999 to 2010. A retrospective study from January 1999 to December 2010 evaluated the results of onychomycosis positive direct mycological exams (DME) - for yeast and realized in the Hemato(r) Clinical Laboratory. Women were the most affected by onychomycosis which occur preferentially in adults, and the toenails are the favorite yeast targets. The prevalent yeasts were Candida tropicalis and C. krusei. PMID- 26375022 TI - Effect of Grape Polyphenols on Blood Pressure: A Meta-Analysis of Randomized Controlled Trials. AB - BACKGROUND: The effect of grape polyphenols on blood pressure remains unclear, which we aimed to address via a meta-analysis study. METHODS: We conducted study trial searches in PubMed, Embase, and the Cochrane Library databases. Summary estimates of weighted mean differences and 95% confidence intervals were obtained by using fixed-effects models. Subgroup analyses were performed to identify the source of heterogeneity. The protocol details of our meta-analysis have been submitted to the international database of prospectively registered systematic reviews (registration number CRD42015019196). RESULTS: Ten studies were included in the present meta-analysis. Our results showed daily grape polyphenol intake could significantly reduce systolic blood pressure by 1.48 mmHg when compared to control subjects (12 comparisons; -1.48 [-2.79 to -0.16] mmHg; P = 0.03). Subgroup analyses indicated larger reduction was identified in the intake of low dose of grape polyphenols (< 733 mg/day, median level of the included studies) or patients with metabolic syndrome. Contrarily, diastolic blood pressure was not significantly decreased in the grape polyphenols group as compared to controls. No significant heterogeneity or publication bias was detected in the meta analysis of either systolic or diastolic blood pressure. CONCLUSIONS: Daily grape polyphenol intake can significantly reduce the systolic blood pressure in humans, although the reduction is modest when compared with anti-hypertensive medications. Larger, better designed trials, that specifically include hypertensive subjects, are required to verify our results in the future. PMID- 26375023 TI - Enhanced Antitumor Efficacy and Reduced Toxicity of Docetaxel Loaded Estradiol Functionalized Stealth Polymeric Nanoparticles. AB - In spite of extensive research over the decades, breast cancer treatment is still a major challenge due to nonspecific distribution of the chemotherapeutics. This void can be filled by restricting the distribution of chemotherapeutics toward the cancerous cells. In the present report estradiol (E2) functionalization of docetaxel (DTX) loaded PLGA nanoparticles was supposed to have specific distribution of DTX to cancerous cells simultaneously avoiding the nonspecific distribution toward the normal cells. In line, E2-PEG-PLGA conjugate was synthesized and characterized by FTIR and NMR spectroscopy. Extensive optimization of different process variables resulted in the formation of spherical E2-PEG-PLGA NPs in the size range of 228.5 +/- 11.8 nm and entrapment efficiency of 94.25 +/- 2.49. Trehalose (5% w/v) resulted in the formation of a fluffy, easy to redisperse freeze-dried cake of nanoparticles. PXRD analysis revealed the amorphous nature of DTX encapsulated within the nanoparticles. X-ray photoelectron spectroscopy confirmed the presence of E2 over the surface of nanoparticles. In line with our hypothesis, cellular uptake studies on ER positive MCF-7 cells revealed relatively higher uptake and efficient localization into the nuclear region of E2-PEG-PLGA NPs in comparison with plain counterparts, while in the case of ER negative HeLa cells E2-PEG-PLGA NPs showed no difference in fluorescence pattern as compared to MCF-7 cells incubated with unmodified nanoformulation, indicating nonspecific delivery of DTX. Moreover, MTT assay revealed relatively higher cytotoxicity of E2-PEG-PLGA NPs in comparison with free DTX. Furthermore, in vivo pharmacokinetic studies revealed 9.36- and 4.79 fold enhancement in circulation half-life and AUC(0-infinity), respectively, of E2-PEG-PLGA NPs in comparison with Taxotere. In vivo antitumor efficacy in DMBA induced rat model demonstrated significant reduction in tumor volume in comparison with the plain counterpart (PLGA-NPs) and a marketed formulation, Taxotere. Moreover, the safety of the estradiol functionalized PLGA NPs was confirmed by hepato- and nephrotoxicity studies. PMID- 26375025 TI - Iron restriction in sickle cell anemia: Time for controlled clinical studies. PMID- 26375024 TI - PKC and AKT Modulate cGMP/PKG Signaling Pathway on Platelet Aggregation in Experimental Sepsis. AB - Sepsis severity has been positively correlated with platelet dysfunction, which may be due to elevations in nitric oxide (NO) and cGMP levels. Protein kinase C, Src kinases, PI3K and AKT modulate platelet activity in physiological conditions, but no studies evaluated the role of these enzymes in platelet aggregation in sepsis. In the present study we tested the hypothesis that in sepsis these enzymes positively modulate upstream the NO-cGMP pathway resulting in platelet inhibition. Rats were injected with lipopolysaccharide (LPS, 1 mg/kg, i.p.) and blood was collected after 6 h. Platelet aggregation was induced by ADP (10 MUM). Western blotting assays were carried out to analyze c-Src and AKT activation in platelets. Intraplatelet cGMP levels were determined by enzyme immunoassay kit. Phosphorylation of c-SRC at Tyr416 was the same magnitude in platelets of control and LPS group. Incubation of the non-selective Src inhibitor PP2 (10 MUM) had no effect on platelet aggregation of LPS-treated rats. LPS increased intraplatelet cGMP levels by 5-fold compared with control group, which was accompanied by 76% of reduction in ADP-induced platelet aggregation. The guanylyl cyclase inhibitor ODQ (25 MUM) and the PKG inhibitor Rp-8-Br-PET-cGMPS (25 MUM) fully reversed the inhibitory effect of LPS on platelet aggregation. Likewise, the PKC inhibitor GF109203X (10 MUM) reversed the inhibition by LPS of platelet aggregation and decreased cGMP levels in platelets. AKT phosphorylation at Thr308 was significantly higher in platelets of LPS compared with control group, which was not reduced by PI3K inhibition. The AKT inhibitor API-1 (20 MUM) significantly increased aggregation and reduced cGMP levels in platelets of LPS group. However, the PI3K inhibitor wortmannin and LY29004 had no effect on platelet aggregation of LPS-treated rats. Therefore, inhibition of ADP-induced platelet aggregation after LPS injection is mediated by cGMP/PKG-dependent mechanisms, and PKC and AKT act upstream upregulating this pathway. PMID- 26375026 TI - Effects of Ultrasound on Spoilage Microorganisms, Quality, and Antioxidant Capacity of Postharvest Cherry Tomatoes. AB - Mature-green cherry tomato fruits (Lycopersicon esculentum cv. Jinyu) were exposed to different power densities of ultrasound (66.64, 106.19, and 145.74 W/L) at 25 degrees C to study ultrasound non-thermal effects on the storage properties. Among the three levels of ultrasound irradiation, 106.19 W/L ultrasound was effective in reducing the spoilage microorganisms, delaying postharvest ripening through inhibiting ethylene production and respiration rates, and consequently maintaining fruit firmness, flavor, enzyme activities, antioxidants (total phenolics, total flavonoids), and the total antioxidant capacity of cherry tomatoes. The 66.64 W/L ultrasound had similar effects but to a lesser extent. Meanwhile, although 145.74 W/L ultrasound resulted in higher content of ascorbic acid (AA), it showed many negative effects on the storage quality of fruits. These results demonstrated that ultrasound of appropriate power density had great potentials in inhibiting decay, maintaining flavor and nutritional quality of cherry tomatoes. PRACTICAL APPLICATION: Recently, ultrasound has been considered as a multifunctional pretreatment method for the preservation of postharvest fruits and vegetables. Although the preservation effects were slight because of the screening of the thermal effects, its non thermal effects presented potentials in improving storage quality of cherry tomato. Further studies are needed to explore the combinations between ultrasound with heating as well as other postharvest preservation technologies to enhance the effects of ultrasound. These explorations would facilitate the large-scale application of ultrasound in the preservation of fresh fruits and vegetables. PMID- 26375027 TI - Successful Treatment of Combined Aspergillus and Cytomegalovirus Abscess in Brain and Lung After Liver Transplant for Toxic Fulminant Hepatitis. AB - Invasive aspergillosis is one of the most important and fatal complications after liver transplant, especially in patients with involvement of the central nervous system. We present a case of a patient who developed cerebral and pulmonary aspergillosis, coinfected with cytomegalovirus, after liver transplant for toxic fulminant hepatitis. The patient was treated successfully with neurosurgical intervention and voriconazole. Voriconazole is considered more effective in cerebral aspergillosis than other anti-fungal agents due to the greater penetration into central nervous system and higher cerebrospinal fluid and brain tissue levels. PMID- 26375029 TI - The Search for a Volatile Human Specific Marker in the Decomposition Process. AB - In this study, a validated method using a thermal desorber combined with a gas chromatograph coupled to mass spectrometry was used to identify the volatile organic compounds released during decomposition of 6 human and 26 animal remains in a laboratory environment during a period of 6 months. 452 compounds were identified. Among them a human specific marker was sought using principle component analysis. We found a combination of 8 compounds (ethyl propionate, propyl propionate, propyl butyrate, ethyl pentanoate, pyridine, diethyl disulfide, methyl(methylthio)ethyl disulfide and 3-methylthio-1-propanol) that led to the distinction of human and pig remains from other animal remains. Furthermore, it was possible to separate the pig remains from human remains based on 5 esters (3-methylbutyl pentanoate, 3-methylbutyl 3-methylbutyrate, 3 methylbutyl 2-methylbutyrate, butyl pentanoate and propyl hexanoate). Further research in the field with full bodies has to corroborate these results and search for one or more human specific markers. These markers would allow a more efficiently training of cadaver dogs or portable detection devices could be developed. PMID- 26375030 TI - Persistence and Viability of Lecanicillium lecanii in Chinese Agricultural Soil. AB - The entomopathogenic fungus L. lecanii has been developed as biopesticides and used widely for biological control of several insects in agricultural practice. Due to the lack of isolation/count methods for L. lecanii in soil, the persistence of this fungus in soil appears to have attracted no attention. A selective medium and count method for L. lecanii in soil based on cetyl trimethyl ammonium bromide (CTAB) was developed, and then the persistence and viability of this fungus in soil were investigated under field conditions between 2012 and 2014. The results showed that the rate of recovery for L. lecanii in soil on the selective CTAB medium was satisfactory. The minimum CFUs for L. lecanii on the selective medium (0.5 g/L CTAB) was about 102 conidia/g soil. The L. lecanii density in soil declined quickly in the first month after inoculation with fungal conidia, kept stable for 6 to 10 months, and then decreased gradually until undetectable. L. lecanii could persist for at least 14 months in the agricultural soil of northern China. The colony growth, conidia yield and germination rate on plates, as well as the median lethal concentration or times (LC50 or LT50) to aphids, mycelium growth in aphids and sporulation on aphids of L. lecanii did not change significantly during the persistence in soil. In general, the count method developed here was a very useful tool for monitoring the dynamics of natural or introduced L. lecanii populations in soil, and the data on the persistence of L. lecanii in soil reported here were helpful for biological control and environmental risk assessment. PMID- 26375028 TI - Genetic Contribution of Variants near SORT1 and APOE on LDL Cholesterol Independent of Obesity in Children. AB - OBJECTIVE: To assess potential effects of variants in six lipid modulating genes (SORT1, HMGCR, MLXIPL, FADS2, APOE and MAFB) on early development of dyslipidemia independent of the degree of obesity in children, we investigated their association with total (TC), low density lipoprotein (LDL-C), high density lipoprotein (HDL-C) cholesterol and triglyceride (TG) levels in 594 children. Furthermore, we evaluated the expression profile of the candidate genes during human adipocyte differentiation. RESULTS: Expression of selected genes increased 10(1) to >10(4) fold during human adipocyte differentiation, suggesting a potential link with adipogenesis. In genetic association studies adjusted for age, BMI SDS and sex, we identified significant associations for rs599839 near SORT1 with TC and LDL-C and for rs4420638 near APOE with TC and LDL-C. We performed Bayesian modelling of the combined lipid phenotype of HDL-C, LDL-C and TG to identify potentially causal polygenic effects on this multi-dimensional phenotype and considering obesity, age and sex as a-priori modulating factors. This analysis confirmed that rs599839 and rs4420638 affect LDL-C. CONCLUSION: We show that lipid modulating genes are dynamically regulated during adipogenesis and that variants near SORT1 and APOE influence lipid levels independent of obesity in children. Bayesian modelling suggests causal effects of these variants. PMID- 26375031 TI - Fluid Intelligence and Automatic Neural Processes in Facial Expression Perception: An Event-Related Potential Study. AB - The relationship between human fluid intelligence and social-emotional abilities has been a topic of considerable interest. The current study investigated whether adolescents with different intellectual levels had different automatic neural processing of facial expressions. Two groups of adolescent males were enrolled: a high IQ group and an average IQ group. Age and parental socioeconomic status were matched between the two groups. Participants counted the numbers of the central cross changes while paired facial expressions were presented bilaterally in an oddball paradigm. There were two experimental conditions: a happy condition, in which neutral expressions were standard stimuli (p = 0.8) and happy expressions were deviant stimuli (p = 0.2), and a fearful condition, in which neutral expressions were standard stimuli (p = 0.8) and fearful expressions were deviant stimuli (p = 0.2). Participants were required to concentrate on the primary task of counting the central cross changes and to ignore the expressions to ensure that facial expression processing was automatic. Event-related potentials (ERPs) were obtained during the tasks. The visual mismatch negativity (vMMN) components were analyzed to index the automatic neural processing of facial expressions. For the early vMMN (50-130 ms), the high IQ group showed more negative vMMN amplitudes than the average IQ group in the happy condition. For the late vMMN (320-450 ms), the high IQ group had greater vMMN responses than the average IQ group over frontal and occipito-temporal areas in the fearful condition, and the average IQ group evoked larger vMMN amplitudes than the high IQ group over occipito-temporal areas in the happy condition. The present study elucidated the close relationships between fluid intelligence and pre-attentive change detection on social-emotional information. PMID- 26375032 TI - Transplacental Administration of Rosiglitazone Attenuates Hyperoxic Lung Injury in a Preterm Rabbit Model. AB - INTRODUCTION: Continuous improvements in perinatal care have allowed the survival of increasingly more prematurely born infants. The establishment of respiration in an extremely immature yet still developing lung results in chronic lung injury with significant mortality and morbidity. We experimentally evaluated a novel medical strategy to prevent hyperoxia-induced lung injury by prenatal rosiglitazone. MATERIALS AND METHODS: Pregnant rabbits were injected with saline or rosiglitazone (3 mg/kg) 48 and 24 h prior to preterm delivery at 28 days of gestation (term = 31 days). The pups were held in normoxia (21% O2) or hyperoxia (>95% O2), and assessment was done at three different time points (1 h, 24 h and 7 days). RESULTS: The administration of rosiglitazone resulted in a significant decrease in tissue damping (resistance) on day 7. Furthermore, significantly increased expression of vascular endothelial growth factor, fetal liver kinase 1 and surfactant protein B immediately after delivery was noted by immunohistochemistery. On day 7, there was a more mature lung parenchymal architecture in rosiglitazone-exposed pups. DISCUSSION: In a preterm rabbit model, prenatal maternal administration of rosiglitazone attenuates neonatal hyperoxic lung injury and results in a more mature pulmonary parenchyma. PMID- 26375033 TI - Survey of Ixodes pacificus Ticks in California Reveals a Diversity of Microorganisms and a Novel and Widespread Anaplasmataceae Species. AB - Ixodes pacificus ticks can harbor a wide range of human and animal pathogens. To survey the prevalence of tick-borne known and putative pathogens, we tested 982 individual adult and nymphal I. pacificus ticks collected throughout California between 2007 and 2009 using a broad-range PCR and electrospray ionization mass spectrometry (PCR/ESI-MS) assay designed to detect a wide range of tick-borne microorganisms. Overall, 1.4% of the ticks were found to be infected with Borrelia burgdorferi, 2.0% were infected with Borrelia miyamotoi and 0.3% were infected with Anaplasma phagocytophilum. In addition, 3.0% were infected with Babesia odocoilei. About 1.2% of the ticks were co-infected with more than one pathogen or putative pathogen. In addition, we identified a novel Anaplasmataceae species that we characterized by sequencing of its 16S rRNA, groEL, gltA, and rpoB genes. Sequence analysis indicated that this organism is phylogenetically distinct from known Anaplasma species with its closest genetic near neighbors coming from Asia. The prevalence of this novel Anaplasmataceae species was as high as 21% at one site, and it was detected in 4.9% of ticks tested statewide. Based upon this genetic characterization we propose that this organism be called 'Candidatus Cryptoplasma californiense'. Knowledge of this novel microbe will provide awareness for the community about the breadth of the I. pacificus microbiome, the concept that this bacterium could be more widely spread; and an opportunity to explore whether this bacterium also contributes to human or animal disease burden. PMID- 26375035 TI - Circannual Testis Changes in Seasonally Breeding Mammals. AB - In the non-equatorial zones of the Earth, species concentrate their reproductive effort in the more favorable season. A consequence of seasonal breeding is seasonal testis regression, which implies the depletion of the germinative epithelium, permeation of the blood-testis barrier, and reduced androgenic function. This process has been studied in a number of vertebrates, but the mechanisms controlling it are not yet well understood. Apoptosis was assumed for years to be an important effector of seasonal germ cell depletion in all vertebrates, including mammals, but an alternative mechanism has recently been reported in the Iberian mole as well as in the large hairy armadillo. It is based on the desquamation of meiotic and post-meiotic germ cells as a consequence of altered Sertoli-germ cell adhesion molecule expression and distribution. Desquamated cells are either discarded alive through the epididymis, as in the mole, or subsequently die by apoptosis, as in the armadillo. Also, recent findings on the reproductive cycle of the greater white-toothed shrew at the meridional limits of its distribution area have revealed that the mechanisms controlling seasonal breeding are in fact far more plastic and versatile than initially suspected. Perhaps these higher adaptive capacities place mammals in a better position to face the ongoing climate change. PMID- 26375034 TI - Are Retinal Vessels Calibers Influenced by Blood Pressure Measured at the Time of Retinography Acquisition? AB - BACKGROUND: Retinal arterial narrowing is associated with higher office blood pressure (BP) and ambulatory blood pressure monitoring, and increased incidence of cardiovascular disease, but it is still unknown if the vessel caliber is associated with BP measured at the time of retinography acquisition. METHODS: Retinal arteriolar and venular calibers were measured by the microdensitometric method in 448 patients with hypertension. Participants underwent 24-hours ambulatory blood pressure (24-h ABP) monitoring simultaneously with the retinography acquisition. Association between arteriolar and venular calibers with increase of 10 mmHg in the mean 24-hours, daily, and nightly BP, and with BP measured at the time of retinography, was evaluated by ANOVA and multivariate analyses. RESULTS: Mean 24-hours, daytime and nighttime systolic and diastolic BP were inversely associated with the arteriolar caliber, but not with the venular caliber. Arteriolar caliber decreased -0.8 (95% CI -1.4 to -0.2) MUm per 10-mmHg increase in 24-hours mean systolic BP, adjusted for age, gender, fellow vessel, and duration of hypertension (P = 0.01). The corresponding decreasing in arteriolar caliber by 10 mmHg of increasing in mean diastolic BP was -1.1 MUm ( 2.0 to -0.2, P = 0.02). The decrease of arteriolar caliber by the same increasing of BP measured at the time of retinography was lower and not statistically significant, particularly for mean diastolic BP and outer arterioles calibers: 1.0 (-1.8 to -0.2) MUm in the daytime BP average versus -0.3 (-0.9 to 0.3) at the moment of retinography acquisition. CONCLUSIONS: These findings suggest that the caliber of arteriolar retinal vessels in patients with uncontrolled hypertension are not significantly influenced by blood pressure measured at the time of retinography acquisition. PMID- 26375036 TI - How Do Landscape Structure, Management and Habitat Quality Drive the Colonization of Habitat Patches by the Dryad Butterfly (Lepidoptera: Satyrinae) in Fragmented Grassland? AB - Most studies dealing with species distribution patterns on fragmented landscapes focus on the characteristics of habitat patches that influence local occurrence and abundance, but they tend to neglect the question of what drives colonization of previously unoccupied patches. In a study of the dryad butterfly, we combined classical approaches derived from metapopulation theory and landscape ecology to investigate the factors driving colonization from a recent refugium. In three consecutive transect surveys, we recorded the presence and numbers of imagos in 27 patches of xerothermic grassland and 26 patches of wet meadow. Among the predictors affecting the occurrence and abundance of the dryad, we considered environmental variables reflecting (i) habitat patch quality (e.g., goldenrod cover, shrub density, vegetation height); (ii) factors associated with habitat spatial structure (patch size, patch isolation and fragmentation); and (iii) features of patch surroundings (100-m buffers around patches) that potentially pose barriers or provide corridors. Patch colonization by the dryad was strongly limited by the distance from the species refugium in the region; there was a slight positive effect of shrub density in this respect. Butterfly abundance increased in smaller and more fragmented habitat patches; it was negatively impacted by invasive goldenrod cover, and positively influenced by the density of watercourses in patch surroundings. Nectar plant availability was positively related to species abundance in xerothermic grassland, while in wet meadow the effect was the reverse. We conclude that dryad colonization of our study area is very recent, since the most important factor limiting colonization was distance from the refugium, while the habitat quality of target patches had less relevance. In order to preserve the species, conservation managers should focus on enhancing the quality of large patches and should also direct their efforts on smaller and more fragmented ones, including those with relatively low resource availability, because such habitat fragments have an important role to play for specialist species. PMID- 26375037 TI - Tracing the Cycling and Fate of the Explosive 2,4,6-Trinitrotoluene in Coastal Marine Systems with a Stable Isotopic Tracer, (15)N-[TNT]. AB - 2,4,6-Trinitrotoluene (TNT) has been used as a military explosive for over a hundred years. Contamination concerns have arisen as a result of manufacturing and use on a large scale; however, despite decades of work addressing TNT contamination in the environment, its fate in marine ecosystems is not fully resolved. Here we examine the cycling and fate of TNT in the coastal marine systems by spiking a marine mesocosm containing seawater, sediments, and macrobiota with isotopically labeled TNT ((15)N-[TNT]), simultaneously monitoring removal, transformation, mineralization, sorption, and biological uptake over a period of 16 days. TNT degradation was rapid, and we observed accumulation of reduced transformation products dissolved in the water column and in pore waters, sorbed to sediments and suspended particulate matter (SPM), and in the tissues of macrobiota. Bulk delta(15)N analysis of sediments, SPM, and tissues revealed large quantities of (15)N beyond that accounted for in identifiable derivatives. TNT-derived N was also found in the dissolved inorganic N (DIN) pool. Using multivariate statistical analysis and a (15)N mass balance approach, we identify the major transformation pathways of TNT, including the deamination of reduced TNT derivatives, potentially promoted by sorption to SPM and oxic surface sediments. PMID- 26375038 TI - gamma- and beta-Peptide Foldamers from Common Multifaceted Building Blocks: Synthesis and Structural Characterization. AB - Structural characterization of 3,4-disubstituted gamma-peptide and 2,3 disubstituted beta-peptide foldamers derived from common multifaceted beta nitromethyl gamma-amino acids and the chemical transformation of the beta nitromethyl group in gamma-peptides into various functional derivatives are reported. The gamma(3,4)-oligomers and alpha,gamma-hybrid peptides showed characteristic C14-and C12-helical conformations in single crystals. Further, the new 2,3-disubstituted acyclic beta-peptide showed the C6-helical conformation despite the poor geometry of H-bonds. PMID- 26375039 TI - Microfabricated Collector-Generator Electrode Sensor for Measuring Absolute pH and Oxygen Concentrations. AB - Fast-scan cyclic voltammetry (FSCV) has attracted attention for studying in vivo neurotransmission due to its subsecond temporal resolution, selectivity, and sensitivity. Traditional FSCV measurements use background subtraction to isolate changes in the local electrochemical environment, providing detailed information on fluctuations in the concentration of electroactive species. This background subtraction removes information about constant or slowly changing concentrations. However, determination of background concentrations is still important for understanding functioning brain tissue. For example, neural activity is known to consume oxygen and produce carbon dioxide which affects local levels of oxygen and pH. Here, we present a microfabricated microelectrode array which uses FSCV to detect the absolute levels of oxygen and pH in vitro. The sensor is a collector-generator electrode array with carbon microelectrodes spaced 5 MUm apart. In this work, a periodic potential step is applied at the generator producing transient local changes in the electrochemical environment. The collector electrode continuously performs FSCV enabling these induced changes in concentration to be recorded with the sensitivity and selectivity of FSCV. A negative potential step applied at the generator produces a transient local pH shift at the collector. The generator-induced pH signal is detected using FSCV at the collector and correlated to absolute solution pH by postcalibration of the anodic peak position. In addition, in oxygenated solutions a negative potential step at the generator produces hydrogen peroxide by reducing oxygen. Hydrogen peroxide is detected with FSCV at the collector electrode, and the magnitude of the oxidative peak is proportional to absolute oxygen concentrations. Oxygen interference on the pH signal is minimal and can be accounted for with a postcalibration. PMID- 26375040 TI - Differences in health risk behaviors across understudied LGBT subgroups. AB - OBJECTIVE: The purpose of the current study was to conduct a large-scale, geographically diverse comparison of health risk behaviors between a broad range of sexual orientation and gender identity groups to more fully understand the health risks of subgroups within the LGBT community. METHOD: A total of 3,279 individuals self-identifying as LGBT (e.g., lesbian, gay, bisexual, pansexual, transgender, genderqueer, and/or another gender or sexual minority) were recruited from across the United States through 2 sequentially implemented online recruitment methods. Participants completed a demographic assessment and the Health Risk Questionnaire (assessing diet and exercise, substance use and smoking, motor vehicle risks, sexual behaviors, violence, and medical risk taking). RESULTS: Significant differences were found across genders for 18 of the 28 health risk behaviors investigated and across sexual orientations for 23 behaviors. Major differences emerged particularly with relation to diet and exercise behaviors, as well as sexual risk-taking, substance use, and medical risk-taking. Groups with notably elevated health risk behaviors included transgender women (diet and exercise behaviors), cisgender men (alcohol-related risk-taking), bisexual participants (substance use), and both transgender men and pansexual participants (self-harm). Differences between transgender participants and genderqueer or nonbinary participants were stark, indicating that these frequently combined groups have distinct health risk profiles. CONCLUSIONS: Results suggest that there are extensive and largely variable levels of engagement in health risk behaviors within the LGBT community. In addition, gender and sexual orientation subcategories that are traditionally collapsed into 1 category (i.e., transgender and bisexual) evidenced strikingly different risks when examined independently. Recommendations for future research and LGBT health promotion efforts are discussed. PMID- 26375041 TI - Structurally-defined, sulfo-phenylated, oligophenylenes and polyphenylenes. AB - We report the synthesis and molecular characterization of structurally defined, sulfo-phenylated, oligo- and polyphenylenes that incorporate a novel tetra sulfonic acid bistetracyclone monomer. The utility of this monomer in the [4 + 2] Diels-Alder cycloaddition to produce well-defined, sulfonated oligophenylenes and pre-functionalized polyphenylene homopolymers is demonstrated. Characterization of the oligophenylenes indicates formation of the meta-meta and para-para adducts in a ~ 1:1 ratio. These functionalized monomers and their subsequent coupling provide a route to prepare novel, sterically encumbered, sulfonated polyphenylenes possessing unprecedented structural control. PMID- 26375042 TI - Surface Reactivity of a Carbonaceous Cathode in a Lithium Triflate/Ether Electrolyte-Based Li-O2 Cell. AB - Li-O2 batteries are currently one of the most advanced and challenging electrochemical systems with the potential to largely overcome the performances of any existing technology for energy storage and conversion. However, these optimistic expectations are frustrated by the still inadequate understanding of the fundamentals of the electrochemical/chemical reactions occurring at the cathode side, as well as within the electrolyte and at the three-phase interface. In this work, we illustrate the evolution of the morphology and composition of a carbonaceous cathode in the first discharge/charge in a Li-O2 cell with an ether based electrolyte by X-ray photoemission spectroscopy, Fourier transform infrared spectroscopy, and transmission electron microscopy. Experiments have been carried out ex situ on electrodes recuperated from electrochemical cells stopped at various stages of galvanostatic discharge and charge. Apparently, a reversible accumulation and decomposition of organic and inorganic precipitates occurs upon discharge and charge, respectively. These precipitations and decompositions are likely driven by electrochemical and chemical parasitic processes due to the reactivity of the cathode carbonaceous matrix. PMID- 26375043 TI - Synthesis of Azabicycles via Cascade Aza-Prins Reactions: Accessing the Indolizidine and Quinolizidine Cores. AB - The first detailed studies of intramolecular aza-Prins and aza-silyl-Prins reactions, starting from acyclic materials, are reported. The methods allow rapid and flexible access toward an array of [6,5] and [6,6] aza-bicycles, which form the core skeletons of various alkaloids. On the basis of our findings on the aza Prins and aza-silyl-Prins cyclizations, herein we present simple protocols for the intramolecular preparation of the azabicyclic cores of the indolizidines and quinolizidines using a one-pot cascade process of N-acyliminium ion formation followed by aza-Prins cyclization and either elimination or carbocation trapping. It is possible to introduce a range of different substituents into the heterocycles through a judicial choice of Lewis acid and solvent(s), with halo-, phenyl-, and amido-substituted azabicyclic products all being accessed through these highly diastereoselective processes. PMID- 26375044 TI - The Effects of Maternal Position and Habitus on Maternal Cardiovascular Parameters as Measured by Cardiac Magnetic Resonance. AB - OBJECTIVE: To evaluate left ventricular stroke volume (LVSV) and cardiac output (CO) according to maternal position and habitus throughout pregnancy and postpartum using serial cardiac magnetic resonance imaging (c-MRI). STUDY DESIGN: This was a prospective study of normotensive nulliparous women using 1.5-T c-MRI performed in both left lateral decubitus and supine positions during three epochs in pregnancy and at 12 weeks' postpartum. Women were stratified according to prepregnancy body mass indices (BMIs) as normal or overweight/obese and compared for LVSV and CO using repeated measures, mixed-random, and fixed-effects model. RESULTS: Between October 2012 and December 2014, 14 normal-weight (BMI 22.2 +/- 1.3) and 9 overweight/obese (BMI 29.1 +/- 2.0) women underwent c-MRI. During early pregnancy, position did not alter LVSV or CO for either cohort. Beginning at 26 to 30 weeks and continuing to 32 to 36 weeks, normal-weight women demonstrated significant positional differences for LVSV and CO (both p < 0.01). In contrast, positional differences did not influence these parameters in overweight/obese women. At 12 weeks' postpartum, all influence of position had dissipated for both cohorts. CONCLUSION: Maternal position has no effect on LVSV or CO during the first half of pregnancy. In the second half, however, only normal-weight women exhibit significant changes in cardiac parameters when comparing the left lateral decubitus with supine position. PMID- 26375045 TI - Abnormal Biochemical Analytes Used for Aneuploidy Screening and Adverse Pregnancy Outcomes in Twin Gestations. AB - OBJECTIVE: The objective of this study was to determine if first- and second trimester biochemical markers for aneuploidy have an association with adverse pregnancy outcomes in twin gestations. STUDY DESIGN: A retrospective cohort study of patients who presented with dichorionic diamniotic twin gestations was performed. Patients with first-trimester low pregnancy-associated plasma protein A (PAPP-A) or low free beta human chorionic gonadotropin (beta-hCG), or second trimester elevated alpha-fetoprotein (AFP), elevated inhibin A, elevated hCG, or low unconjugated estradiol were identified. The rates of adverse pregnancy outcomes were compared between patients with or without abnormal analytes with p < 0.05 used as significance. RESULTS: In this study, 340 pregnancies were included. Patients with a low PAPP-A had an increased risk for delivery < 37 weeks. Patients with an elevated second-trimester hCG had an increased risk for spontaneous delivery < 28 weeks and neonatal intensive care unit (NICU) admission. Patients with an elevated inhibin A had an increased risk of spontaneous delivery at < 37 and NICU admission. Patients with an elevated AFP had an increased risk of a NICU admission. CONCLUSION: Certain abnormal aneuploidy markers are associated with an increased risk of adverse pregnancy outcomes in twin gestations. PMID- 26375046 TI - Cancer Survivors' Use of Fertility Preservation. AB - BACKGROUND: Some cancer diagnoses and treatments can place patients at risk for infertility. The American Society of Clinical Oncology recommends that health care providers address the possibility of infertility with cancer patients who are treated during their reproductive years; however, research suggests that many providers do not disclose the risk of infertility to their patients. This study examines adolescent/young adult (AYA) cancer survivors' use of and costs for fertility preservation (FP) over time. METHODS: The study included 550 AYA cancer survivors diagnosed at the ages of 15 and 39 years between 2006 and 2012. Logistic regression analyses and chi-squared tests were conducted to identify factors associated with FP use, barriers, and expenses. RESULTS: One hundred eighty two (33%) of the AYA survivors took steps to preserve their fertility. Men, survivors who did not have children, those who received chemotherapy, and those who lived in the Northeast (vs. the South) were more likely to have FP. The majority of men using FP used sperm banking (99%), whereas women used egg preservation (40%), embryo preservation (40%), and other methods (37%). On average, women paid more for FP than men (p < 0.001); however, costs for women significantly declined over time (p = 0.021). CONCLUSIONS: The study points to other areas for research in women's health, including the development of educational interventions with patients and providers to reduce gender disparities in FP and ensure timely patient-provider discussions related to fertility issues. PMID- 26375047 TI - The corrected structure of depressoside, an antioxidative iridoid glucoside extracted from the flowers of Gentiana urnula Harry Sm. AB - Three known iridoid glucosides (gentiournoside A, gentiournoside E and depressoside) were isolated from the flowers of Gentiana urnula Harry Sm. through activity-guided fractionations with a 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. All three compounds exhibited excellent DPPH radical scavenging activities (IC50: 10-20 MUmol L(-1)) comparable to that of ascorbic acid and Trolox. However, examination of the NMR data revealed that the reported chemical structure of depressoside, previously isolated from the leaves of G. depressa, needed correcting due to incorrect elucidation around C-7 of the iridane skeleton, and was corrected to 6-beta-(2,3-dihydroxyphenyl)-D-glucosyl 7-O-(2,3 dihydroxybenzoyl)-loganate. Depressoside exhibited a much higher scavenging activity against superoxide radicals (IC50: 45.5 MUmol L(-1)) than the other two extracted compounds (IC50: more than 900 MUmol L(-1)) due to the crucial presence of a pyrogallyl unit. PMID- 26375048 TI - Role of Phragmites australis (common reed) for heavy metals phytoremediation of estuarine sediments. AB - The ability of Phragmites australis to take up heavy metals (Co, Ni, Mo, Cd, Pb, Cr, Cu, Fe, Mn, Zn, and Hg) and other trace elements (As, Se, Ba), from estuarine sediments was investigated using a pilot plant experimental approach. Bioaccumulation (BCF) and translocation factors (TF) were calculated in vegetative and senescence periods for two populations of P. australis, from contaminated (MIC) and non-contaminated (GAL) estuarine sediments, respectively, both growing in estuarine contaminated sediment (RIA) from ria del Carmen y Boo, Santander Bay, Spain. The highest BCF values were obtained for Ni (0.43), Ba (0.43) Mo (0.36), Cr (0.35), and Cd (0.31) for plants collected from site GAL following the senescence period. The highest BCF values recorded for plants collected from MIC following the senescence period were for Mo (0.22) and Cu (0.22). Following senescence, plants collected from GAL and MIC presented TF>1 for Ni, Mo, Se, and Zn, and in addition plants collected from MIC presented TF>1 for Ba, Cr, and Mn. A substantial increase of Micedo's rhizosphere, six times higher than Galizano's rhizosphere, suggested adaptation to contaminated sediment. The evaluated communities of P. australis demonstrated their suitability for phytoremediation of heavy metals contaminated estuarine sediments. PMID- 26375049 TI - Clinical correlates of chronotypes in young persons with mental disorders. AB - While important changes in circadian rhythms take place during adolescence and young adulthood, it is unclear how circadian profiles during this period relate to emerging mental disorders. This study aimed to: (i) characterise morningness eveningness preference in young people with primary anxiety, depression, bipolar or psychotic disorders as compared to healthy controls, and (ii) to investigate associations between morningness-eveningness preference and the severity of psychiatric symptoms. Four hundred and ninety-six males and females aged between 12 and 30 years were divided into five groups according to primary diagnosis. The Hamilton Depression Rating Scale and the Brief Psychiatric Rating Scale were administered by a research psychologist and participants completed the Kessler Psychological Distress Scale and the Horne-Ostberg Morningness-Eveningness Questionnaire (ME). ME scores were significantly lower (i.e. higher levels of "eveningness") in all patient diagnosis subgroups compared to the control group. The psychosis group had higher ME scores than the depression and anxiety groups. Compared to the control group, the anxiety, depression and bipolar subgroups had a significantly higher proportion of "moderate evening" types, with a similar trend for the psychosis group. The proportion of "extreme evening" types was significantly higher in the anxiety and depression subgroups than in the control group. Lower ME scores correlated with worse psychological distress in males from the bipolar group. Lower ME scores correlated with higher depression severity in females with depression and in males with bipolar disorder. These results suggest that young persons with various mental disorders, especially those with affective disorders, present with a stronger "eveningness" preference and higher rates of evening chronotypes than healthy controls from the same age group. Later chronotypes were generally associated with worse psychological distress and symptoms severity. These associations were modulated by sex and primary diagnosis. PMID- 26375050 TI - Relationship Between Parental and Adolescent eHealth Literacy and Online Health Information Seeking in Taiwan. AB - This study examined the relationship between parental and adolescent eHealth literacy and its impact on online health information seeking. Data were obtained from 1,869 junior high school students and 1,365 parents in Taiwan in 2013. Multivariate analysis results showed that higher levels of parental Internet skill and eHealth literacy were associated with an increase in parental online health information seeking. Parental eHealth literacy, parental active use Internet mediation, adolescent Internet literacy, and health information literacy were all related to adolescent eHealth literacy. Similarly, adolescent Internet/health information literacy, eHealth literacy, and parental active use Internet mediation, and parental online health information seeking were associated with an increase in adolescent online health information seeking. The incorporation of eHealth literacy courses into parenting programs and school education curricula is crucial to promote the eHealth literacy of parents and adolescents. PMID- 26375051 TI - A kinematic analysis of the spine during rugby scrummaging on natural and synthetic turfs. AB - Artificial surfaces are now an established alternative to grass (natural) surfaces in rugby union. Little is known, however, about their potential to reduce injury. This study characterises the spinal kinematics of rugby union hookers during scrummaging on third-generation synthetic (3G) and natural pitches. The spine was sectioned into five segments, with inertial sensors providing three-dimensional kinematic data sampled at 40 Hz/sensor. Twenty-two adult, male community club and university-level hookers were recruited. An equal number were analysed whilst scrummaging on natural or synthetic turf. Players scrummaging on synthetic turf demonstrated less angular velocity in the lower thoracic spine for right and left lateral bending and right rotation. The general reduction in the range of motion and velocities, extrapolated over a prolonged playing career, may mean that the synthetic turf could result in fewer degenerative injuries. It should be noted, however, that this conclusion considers only the scrummaging scenario. PMID- 26375052 TI - Framing Obesity: How News Frames Shape Attributions and Behavioral Responses. AB - Based on a public health model of obesity, this study set out to examine whether a news article reporting the obesity issue in a societal versus individual frame would increase perceptions of societal responsibilities for the obesity problem and motivate responsibility-taking behaviors. Responsibility-taking behaviors were examined at 3 levels: personal, interpersonal, and societal. Data from a Web based experiment revealed significant framing effects on behaviors via causal and treatment responsibility attributions. The societal frame increased societal causal and treatment attribution, which led to greater likelihoods of interpersonal and social responsibility-taking behaviors as well as personal behaviors. Our findings suggest that news framing can be an effective venue for raising awareness of obesity as a societal issue and mobilizing collective efforts. PMID- 26375053 TI - Ibrutinib selectively and irreversibly targets EGFR (L858R, Del19) mutant but is moderately resistant to EGFR (T790M) mutant NSCLC Cells. AB - Through comprehensive comparison study, we found that ibrutinib, a clinically approved covalent BTK kinase inhibitor, was highly active against EGFR (L858R, del19) mutant driven NSCLC cells, but moderately active to the T790M 'gatekeeper' mutant cells and not active to wild-type EGFR NSCLC cells. Ibrutinib strongly affected EGFR mediated signaling pathways and induced apoptosis and cell cycle arrest (G0/G1) in mutant EGFR but not wt EGFR cells. However, ibrutinib only slowed down tumor progression in PC-9 and H1975 xenograft models. MEK kinase inhibitor, GSK1120212, could potentiate ibrutinib's effect against the EGFR (L858R/T790M) mutation in vitro but not in vivo. These results suggest that special drug administration might be required to achieve best clinical response in the ongoing phase I/II clinical trial with ibrutinib for NSCLC. PMID- 26375054 TI - Therapeutic efficacy of tumor-targeting Salmonella typhimurium A1-R on human colorectal cancer liver metastasis in orthotopic nude-mouse models. AB - Liver metastasis is the most frequent cause of death from colon and other cancers. Generally, liver metastasis is recalcitrant to treatment. The aim of this study is to determine the efficacy of tumor-targeting Salmonella typhimurium A1-R on liver metastasis in orthotopic mouse models. HT-29 human colon cancer cells expressing red fluorescent protein (RFP) were used in the present study. S. typhimurium A1-R infected HT-29 cells in a time-dependent manner, inhibiting cancer-cell proliferation in vitro. S. typhimurium A1-R promoted tumor necrosis and inhibited tumor growth in a subcutaneous tumor mouse model of HT-29-RFP. In orthotopic mouse models, S. typhimurium A1-R targeted liver metastases and significantly reduced their growth. The results of this study demonstrate the future clinical potential of S. typhimurium A1-R targeting of liver metastasis. PMID- 26375056 TI - Bradykinin Impairs and HOE 140 does not Protect Rat Hindlimb Skeletal Muscle Against Tourniquet-induced Reperfusion Injury. AB - BACKGROUND: Bradykinin (BK) is used in different tissues. Dose-dependent studies have demonstrated that low doses protect against ischemia/reperfusion (I/R) injury while higher doses lead to adverse effects. Although the beneficial effects of BK infusion were observed in myocardium, its role on the I/R impact in skeletal muscle (SM) has not been fully clarified. OBJECTIVE: This study was carried out to evaluate the effects of BK, administered in the hindlimbs of rats subjected to I/R. METHODS: The study design included three experimental groups: Group 1 control (saline), Group 2 (bradykinin), and Group 3 (HOE 140, a BK2 receptor blocker). In all three groups, rats were subjected to hindlimb ischemia for a total of 2 h followed by continuous 4 h of reperfusion with pharmacological interventions. The methods include analysis of enzymes (lactate dehydrogenase-LDH and creatinine phosphokinase-CPK), cell membrane marker of injury (malondialdeyde MDA), recruitment of neutrophils (myeloperoxidase-MPO), and apoptosis index (immunohistochemistry TUNEL in situ peroxidase dead end). RESULTS: Except for the apoptotic index, all parameters studied were shown to be elevated in the reperfusion group intervened with BK. The blocking of BK2 receptors by HOE 140 did not affect the I/R injury. CONCLUSION: After 2 h of total ischemia, infusion of bradykinin during 4 h of reperfusion, worsened the I/R injury in the hindlimb skeletal muscle. PMID- 26375055 TI - CDK1 phosphorylation of TAZ in mitosis inhibits its oncogenic activity. AB - The transcriptional co-activator with PDZ-binding motif (TAZ) is a downstream effector of the Hippo tumor suppressor pathway, which plays important roles in cancer and stem cell biology. Hippo signaling inactivates TAZ through phosphorylation (mainly at S89). In the current study, we define a new layer of regulation of TAZ activity that is critical for its oncogenic function. We found that TAZ is phosphorylated in vitro and in vivo by the mitotic kinase CDK1 at S90, S105, T326, and T346 during the G2/M phase of the cell cycle. Interestingly, mitotic phosphorylation inactivates TAZ oncogenic activity, as the non phosphorylatable mutant (TAZ-S89A/S90A/S105A/T326A/T346A, TAZ-5A) possesses higher activity in epithelial-mesenchymal transition, anchorage-independent growth, cell migration, and invasion when compared to the TAZ-S89A mutant. Accordingly, TAZ-5A has higher transcriptional activity compared to the TAZ-S89A mutant. Finally, we show that TAZ-S89A or TAZ-5A (to a greater extent) was sufficient to induce spindle and centrosome defects, and chromosome misalignment/missegregation in immortalized epithelial cells. Together, our results reveal a previously unrecognized connection between TAZ oncogenicity and mitotic phospho-regulation. PMID- 26375057 TI - Pelvic tilt and movement during total hip arthroplasty in the lateral decubitus position. AB - OBJECTIVES: Total hip arthroplasty (THA) is often performed in the lateral decubitus (lateral) position. In this position, the pelvis may have various degrees of tilt leading to implant malposition. We sought to quantify the pelvic tilt in lateral position and further pelvic movement during surgery. METHODS: In 95 cases with primary THA, three-dimensional pelvic tilts were quantified by superimposing images reconstructed from CT data onto antero-posterior radiographs taken in lateral position at set-up and after cup placement. Pelvises were fixed with a device compressing anterior superior iliac spines and sacrum. RESULTS: Various degrees of pelvic tilt occurred compared to the supine position; sagittal: -3.1 degrees (-25.5 degrees to 10.2 degrees ), axial: 3.9 degrees ( 8.4 degrees to 17 degrees ), coronal: 0.9 degrees (-11.9 degrees to 13.2 degrees ). Absolute changes more than 5 degrees were observed 43%, 47%, and 12% in the sagittal, axial, and coronal planes, respectively. The more preoperative posterior pelvic tilt resulted in the more change in the sagittal plane. Further pelvic movement of about 3 degrees in three planes were observed ranging from 11 degrees to 20 degrees after cup placement. CONCLUSION: This study showed various pelvic tilt and movement during THA. As pelvic tilt directly alters the cup orientation, its changes should be well understood. Improved tools for positioning and holding the pelvis are required. PMID- 26375059 TI - Considerations for orthotopic diversions in women. AB - PURPOSE OF REVIEW: This article overviews current controversies in the field of orthotopic bladder substitution (OBS) in women. RECENT FINDINGS: For patients scheduled for OBS, current evidence suggests that a preoperatively obtained biopsy of the bladder neck is equivalent to performance of an intraoperative frozen section analysis of the distal urethral margin. Women with lymph node tumor or bladder trigone involvement are not at higher risk for urethral recurrence and can, therefore, undergo OBS. Current evidence is not supportive of any type of antirefluxive implantation technique for the protection of the upper tract in patients with ileal neobladder. Facilitating access to the upper tract is important for straightforward follow-up of patients. Although recent studies have shown that robotic urinary diversion with intracorporeal neobladder is technically feasible, they have failed to show that functional outcomes after robotic urinary diversion are superior to open surgery. In order to prevent the formation of neobladder-vaginal fistula an omental transfer with interposition between the reconstructed anterior vaginal wall and the posterior neobladder should be considered. SUMMARY: Surgical meticulousness, but not the technique itself, is important for improved functional outcomes of patients with urinary diversion. Novel surgical techniques need to concentrate around the question of how to improve surgical meticulousness during the preparation of critical anatomical structures at radical pelvic surgery. PMID- 26375060 TI - How are we going to train a generation of radiologists (and urologists) to read prostate MRI? AB - PURPOSE OF REVIEW: Multiparametric MRI has gained tremendous importance in the daily practice for patients at risk or diagnosed with prostate cancer. Interpretation of multiparametric-MRI is a complex task, supposedly restricted to experienced radiologists. The purpose of this review is to analyze fundamentals of multiparametric-MRI interpretation and to describe how multiparametric-MRI training could be organized. RECENT FINDINGS: Recently, professional guidelines have been published to provide technical and interpretation frameworks and harmonize multiparametric-MRI practice, but the question of physicians training in prostate multiparametric-MRI reading is still pending. What kind of education, practice, and training makes a radiologist able to reliably interpret a prostate multiparametric-MRI? How can findings be reported to be easily understood? How much experience is needed? How can we train urologists and other physicians to review the examinations they request? Is double-reading necessary? SUMMARY: An institutional-based competency certification process for prostate multiparametric MRI interpretation may encourage nonspecialized radiologists to qualify for prostate imaging in a standardized and reproducible way, exactly as urologists need it. PMID- 26375058 TI - [V Guideline of the Brazilian Society of Cardiology on Acute Myocardial Infarction Treatment with ST Segment Elevation]. PMID- 26375140 TI - Running Variability Could Change with Aging and Running Speed. PMID- 26375141 TI - Response. PMID- 26375142 TI - Parathyroid Allotransplant With a New Technique: A Prospective Clinical Trial. AB - OBJECTIVES: Parathyroid allotransplant is a valuable alternative in treating permanent hypoparathyroidism. However, it is a difficult process that requires several trained staff and advanced laboratory equipment, which makes the costs high. Here, we identify a new parathyroid allotransplant technique. MATERIALS AND METHODS: After obtaining informed consent from patients, parathyroid cell suspensions obtained from 4 donors who had undergone a subtotal parathyroidectomy owing to chronic renal failure were transplanted in 10 patients with permanent hypoparathyroidism after short-term cell cultivation. Prednisolone were used as immunosuppressant for the first 10 days and discontinued thereafter. RESULTS: Allograft function was observed in 7 patients (70%) at a mean follow-up of 12 months. Daily oral calcium and vitamin D supplementations discontinued totally in 7 patients. No major or minor complication was observed. CONCLUSIONS: Our technique is simple, fast, and has a low cost, with a 70% success rate at a mean follow-up of 12 months. It requires few staff, minimal equipment, and short-term immunosuppressant use for maintenance. The technical developments of parathyroid allotransplant, as mentioned in this study, may be important in treating permanent hypoparathyroidism. PMID- 26375143 TI - In Memory: Laurie M. Gunter, PhD, RN, FAAN March 5, 1922-June 15, 2015. PMID- 26375144 TI - Dehydration in the Older Adult. AB - Dehydration affects 20% to 30% of older adults. It has a greater negative outcome in this population than in younger adults and increases mortality, morbidity, and disability. Dehydration is often caused by water deprivation in older adults, although excess water loss may also be a cause. Traditional markers for dehydration do not take into consideration many of the physiological differences present in older adults. Clinical assessment of dehydration in older adults poses different findings, yet is not always diagnostic. Treatment of dehydration should focus on prevention and early diagnosis before it negatively effects health and gives rise to comorbidities. The current article discusses what has most thoroughly been studied; the best strategies and assessment tools for evaluation, diagnosis, and treatment of dehydration in older adults; and what needs to be researched further. [Journal of Gerontological Nursing, 41(9), 8-13.]. PMID- 26375145 TI - Looking Ahead After 50 Years of Medicare. AB - Fifty years of Medicare have led to enormous improvements in care of older adults in the United States. Policy changes in Medicare and Medicaid have undergirded the care of older adults and the workforce and professional development of nurses and advanced practice nurses. Reflecting on the decades of change in these 50 years and the context in which these changes occurred can prepare health care providers for future strategies to address needs of the rapidly growing older adult population. PMID- 26375146 TI - Frail Older Adults' Experiences With a Proactive, Nurse-Led Primary Care Program: A Qualitative Study. AB - The aim of the current study was to explore frail older adults' perceptions and experiences with a proactive, integrated nurse-led primary care program. A qualitative study nested within a randomized trial in primary care was conducted. In total, 11 semistructured interviews were conducted in a subsample of participants who received nurse-led care in the intervention group. Generally, proactive, nurse-led care was well-received and four different nursing roles were observed: (a) monitor, (b) director, (c) coach, and (d) visitor. The monitor role (i.e., observing and assessing potential risks) was perceived as the most important. The relationship with the nurse, timing of visits, and provided care, as well as tailoring the care to individual needs, were identified as conditions related to appreciation. If the care was well-regarded, older adults were more likely to accept it, which helped them anticipate changes or handle consequences of aging more easily. PMID- 26375148 TI - "Striving for Excellence": Minimum Data Set Coordinators' Perceptions of Their Role in the Nursing Home. AB - The purpose of the current study was to explore how Minimum Data Set (MDS) coordinators perceive their role and the assessment process. Eleven MDS coordinators from 10 geographically dispersed nursing homes (NHs) were interviewed between May and September 2013. Four broad themes emerged from content analysis: (a) information gathering, (b) interdisciplinary coordination, (c) role challenges, and (d) resources. The first two themes referred to key components and competencies in the MDS coordinators' role, the third theme dealt with certain challenges inherent in the role, and the fourth theme highlighted resources that helped address these challenges. The current study provides insight into how MDS coordinators perceive their role, as well as some of the challenges they face to successfully enact that role. The current findings can help inform NH management staff, such as directors of nursing and NH administrators, and policy makers, on how best to support MDS coordinators' work to enable efficient and accurate resident assessment processes. PMID- 26375151 TI - Improving the efficiency of electrochemical CO2 reduction using immobilized manganese complexes. AB - Immobilization of [Mn(bpy)(CO)3Br], (1) and [Mn(bpy((t)Bu)2)(CO)3Br] (2, where (bpy((t)Bu)2) = 4,4'-di-tert-butyl-2,2'-bipyridine) in Nafion/multi-walled carbon nanotubes (MWCNT) on glassy carbon yielded highly active electrodes for the reduction of CO2 to CO in aqueous solutions at pH 7. Films incorporating have significantly improved selectivity towards CO2, with CO : H2 ~ 1 at -1.4 V vs. SCE, exceeding that for the previously reported /MWCNT/Nafion electrode. Furthermore, we report the synthesis and subsequent electrochemical characterization of two new substituted Mn(i) bipyridine complexes, [Mn(bpy(COOH)2)(CO)3Br] (3) and [Mn(bpy(OH)2)(CO)3Br] (4) (where (bpy(COOH)2) = 4,4'-di-carboxy-2,2'-bipyridine and (bpy(OH)2) = 4,4'-di-hydroxy-2,2' bipyridine). Both 3 and 4 were found to have some activity towards CO2 in acetonitrile solutions; however once immobilized in Nafion membranes CO2 reduction was found to not occur at significant levels. PMID- 26375150 TI - Formal Synthesis of Premisakinolide A and C(19)-C(32) of Swinholide A via Site Selective C-H Allylation and Crotylation of Unprotected Diols. AB - Using stereo- and site-selective C-H allylation and crotylation of unprotected diols, an intermediate in the synthesis of premisakinolide A (bistheonellic acid B) that was previously made in 16-27 (LLS) steps is now prepared in only nine steps. This fragment also represents a synthesis of C(19)-C(32) of the actin binding macrodiolide swinholide A. PMID- 26375152 TI - Feminism and/in/as psychology: The public sciences of sex and gender. AB - In our introduction to this special issue on the histories of feminism, gender, sexuality, and the psy-disciplines, we propose the tripartite framework of "feminism and/in/as psychology" to conceptualize the dynamics of their conjoined trajectories and relationship to gender and sexuality from the late 19th through the late 20th centuries. "Feminism and psychology" highlights the tensions between a political movement and a scientific discipline and the efforts of participants in each to problematize the other. "Feminism in psychology" refers to those historical moments when self-identified feminists intervened in psychology to alter its content, methodologies, and populations. We propose, as have others, that these interventions predate the 1970s, the period most commonly associated with the "founding" of feminist psychology. Finally, "feminism as psychology/psychology as feminism" explores the shared ground between psychology and feminism-the conceptual, methodological, and (more rarely) epistemological moments when psychology and feminism made common cause. We suggest that the traffic between feminism and psychology has been persistent, continuous, and productive, despite taking different historically and geographically contingent forms. PMID- 26375153 TI - The personal is scientific: Women, gender, and the production of sexological knowledge in Germany and Austria, 1900-1931. AB - This article addresses the roles women and gender played in the production of sexological knowledge in the early 20th century, particularly in German-speaking Europe. Although existing scholarship focuses almost exclusively on the work of "founding fathers" such as Richard von Krafft-Ebing and Magnus Hirschfeld, women in fact made important contributions to the field. Based on analysis of texts written between 1900 and 1931, this article shows how women were able to successfully mobilize their gender as a privileged form of "situated knowledge," and thereby assert their authority over and superior insights into certain subject areas, namely, female sexualities and sexual difference. At the same time, however, this article also highlights the constraints upon women's gendered standpoint. It shows that women's sexological writing was not just informed by their gender but also by their class and race. Moreover, because gender threatened to cast their work as insufficiently objective and scientific, women cleaved to sexology's rules of evidence and argumentation, and adopted the field's ideological trappings in order to participate in discursive contestations over sexual truths. By interrogating gender, this article introduces much-needed nuance into existing understandings of sexology, and reframes sexology itself as a site wherein new sexual subjectivities were imagined, articulated, and debated. However, it also raises fundamental questions about women sexologists' capacity to create knowledge about women and female sexualities that was truer, more correct, and more authentic than that produced by men. PMID- 26375154 TI - Up the years with the Bettersons: Gender and parent education in interwar America. AB - In the 1920s and 1930s, the parent education movement opened doors for many female psychologists and other child development professionals by providing training and jobs. Female experts in the parent education movement spread the emerging "gospel of child development" to other women-mothers-in a variety of formats. Although psychologists like John B. Watson advocated traditional definitions of motherhood focusing on role adjustment, there is evidence that women psychologists and parent educators introduced ways of thinking about family life that challenged tradition, encouraging role expansion and self-fulfillment. We explore examples provided by women at the Minnesota Institute of Child Welfare who produced radio programs on child rearing. Starting in 1932, advice about child rearing was embedded within stories featuring a fictional family, the Bettersons. The family narrative format provides an opportunity to identify implicit (and sometimes explicit) values and norms informing prescribed roles for mothers, fathers, and children. Analysis suggests that gender roles were shifting in more egalitarian directions, with an awareness of new identity options for both women and men. We explore implications for evaluating the impact of female experts involved in the parent education movement. PMID- 26375155 TI - Treating marriage as "the sick entity": Gender, emotional life, and the psychology of marriage improvement in postwar Britain. AB - This essay examines how marriage relationships came to be constituted as therapeutic objects after WWII and the impact that this had on British postwar understandings of the meaning of marriage. In contrast to prevailing concerns during the interwar decades about sexual dissatisfaction as the chief impediment to marital stability, post-WWII marriage counselors and therapists framed marital harmony as dependent upon spouses' psychological maturity. An inability to sustain a stable marriage was interpreted as a sign of arrested development, most often stemming from a dysfunctional relationship with one or both parents in childhood. This essay reveals that the equal-but-different gender roles that were the cornerstone of the modern "companionate" marriage were crucial to marital counselors and therapists' psychological understanding of marriage as an interpersonal relationship during the decades following WWII. Practitioners gauged therapeutic success not only in accordance with whether or not couples stayed married, but also in terms of the extent to which spouses enthusiastically accepted the adult masculine and feminine spousal roles that the male breadwinning nuclear family required. Moreover, therapists' valuing of the emotional dimensions of marriage made "natural" feminine attributes-such as a presumed ease in establishing loving relationships-a centrally valued aspect of therapeutic work and intimate life more broadly. Far from having a potentially disruptive impact on the presumed naturalness of gender difference (which had been a focus of criticism of psychoanalysis during the interwar decades), the psychoanalytic techniques that were developed to treat marriage problems after WWII were profoundly normalizing. PMID- 26375156 TI - From seduction to sexism: Feminists challenge the ethics of therapist-client sexual relations in 1970s america. AB - Before the 1970s, psychologists and other mental health professionals who had sex with their patients committed no ethical violations. Indeed, the line between seduction and sexual exploitation in the therapy hour was extremely blurry to patients and therapists alike. This article is about how that changed. We focus on feminist psychologists' efforts, through the American Psychological Association Task Force on Sex Bias and Sex Role Stereotyping in Psychotherapeutic Practice, to document and reduce sexism in psychotherapy, including that involving therapist-client sexual relations. We contextualize these efforts within the larger feminist critique of the psy-disciplines that began in the late 1960s, highlighting how psychologists used several feminist strategies to recast seduction as sexism and revise the profession's ethical standards to specifically state that sexual intimacies with clients are unethical. As an example of a feminist intervention into psychology's-and society's-extant gender ideologies, this process highlights the mutually reinforcing entanglements of psychology and feminism, both methodologically and politically. PMID- 26375157 TI - Liberating minds: Consciousness-raising as a bridge between feminism and psychology in 1970s Canada. AB - This article examines the interrelations between psychology and feminism in the work of feminist psychologists and radical feminists in Toronto in the early 1970s. For Canadian feminist psychology as well as for second-wave activism, Toronto was a particular hotspot. It was the academic home of some of the first Canadian feminist psychologists, and was the site of a lively scene of feminists working in established women's organizations along with younger socialist and radical feminists. This article analyzes the interrelations of academic feminist psychology and feminist activism by focusing on consciousness-raising, a practice that promised to bridge tensions between the personal and the political, psychological and social liberation, everyday knowledge and institutionalized knowledge production, theory and practice, as well as the women's movement and other spheres of women's lives. PMID- 26375158 TI - "The name game": Feminist protests of the DSM and diagnostic labels in the 1980s. AB - This article examines protests of the Diagnostic and Statistical Manual of Mental Disorders (DSM) in the mid-1980s to show how feminists working in mental health fields grappled with the tensions between their politics and their work. I argue that the DSM became a site where women attempted to tease out issues relating to gender, professionalization, and the power and stakes of labeling. Feminists privileged a sociological reading of gender, which butted up against mental health care workers' professional investment in psychiatric ones. Women's responses to the DSM, however, reveal that the line between the sociological and the pathological was unclear. This debate over labels is exemplified by a proposal to diagnose rapists as mentally ill. Women's advocates framed sexual assault as an issue of violence against women, rather than an issue of male sexuality. For many women, the American Psychiatric Association's proposal implied that rape was a primarily sexual act, and that male socialization needn't be examined. Others, however, saw this as one more way to label and address bad male behavior; psychiatric treatment might not ultimately put an end to rape, but these women saw any sort of treatment as a step forward. For women professionals, this proposal and the DSM more broadly raised questions about whether the 2 frameworks could be integrated, and whether psychological treatments for social problems were appropriate. PMID- 26375160 TI - Gaining a Critical Mass: A Dose Metric Conversion Case Study Using Silver Nanoparticles. AB - Mass concentration is the standard convention to express exposure in ecotoxicology for dissolved substances. However, nanotoxicology has challenged the suitability of the mass concentration dose metric. Alternative metrics often discussed in the literature include particle number, surface area, and ion release (kinetics, equilibrium). It is unlikely that any single metric is universally applicable to all types of nanoparticles. However, determining the optimal metric for a specific type of nanoparticle requires novel studies to generate supportive data and employ methods to compensate for current analytical capability gaps. This investigation generated acute toxicity data for two standard species (Ceriodaphnia dubia, Pimephales promelas) exposed to five sizes (10, 20, 30, 60, 100 nm) of monodispersed citrate- and polyvinylpyrrolidone coated silver nanoparticles. Particles were sized by various techniques to populate available models for expressing the particle number, surface area, and dissolved fraction. Results indicate that the acute toxicity of the tested silver nanoparticles is best expressed by ion release, and is relatable to total exposed surface area. Particle number was not relatable to the observed acute silver nanoparticle effects. PMID- 26375161 TI - Electron Hopping through Double-Exchange Coupling in a Mixed-Valence Diiminobenzoquinone-Bridged Fe2 Complex. AB - The ability of a benzoquinonoid bridging ligand to mediate double-exchange coupling in a mixed-valence Fe2 complex is demonstrated. Metalation of the bridging ligand 2,5-di(2,6-dimethylanilino)-3,6-dibromo-1,4-benzoquinone (LH2) with Fe(II) in the presence of the capping ligand tris((6-methyl-2 pyridyl)methyl)amine (Me3TPyA) affords the dinuclear complex [(Me3TPyA)2Fe(II)2(L)](2+). The dc magnetic measurements, in conjunction with X ray diffraction and Mossbauer spectroscopy, reveal the presence of weak ferromagnetic superexchange coupling between Fe(II) centers through the diamagnetic bridging ligand to give an S = 4 ground state. The ac magnetic susceptibility measurements, collected in a small dc field, show this complex to behave as a single-molecule magnet with a relaxation barrier of U(eff) = 14(1) cm(-1). The slow magnetic relaxation in the Fe(II)2 complex can be switched off through one-electron oxidation to the mixed-valence congener [(Me3TPyA)2Fe2(L)](3+), where X-ray diffraction and Mossbauer spectroscopy indicate a metal-centered oxidation. The dc magnetic measurements show an S = 9/2 ground state for the mixed-valence complex, stemming from strong ferromagnetic exchange coupling that is best described considering electron hopping through a double-exchange coupling mechanism, with a double-exchange parameter of B = 69(4) cm(-1). In accordance with double-exchange, an intense feature is observed in the near-infrared region and is assigned as an intervalence charge-transfer band. The rate of intervalence electron hopping is comparable to that of the Mossbauer time scale, such that variable-temperature Mossbauer spectra reveal a thermally activated transition from a valence-trapped to detrapped state and provide an activation energy for electron hopping of 63(8) cm(-1). These results demonstrate the ability of quinonoid ligands to mediate electron hopping between high-spin metal centers, by providing the first example of an Fe complex that exhibits double-exchange through an organic bridging ligand and the largest metal-metal separation yet observed in any metal complex with double-exchange coupling. PMID- 26375163 TI - Purification and characterization of detergent stable alkaline protease from Bacillus amyloliquefaciens SP1 isolated from apple rhizosphere. AB - A thermostable extracellular alkaline protease producing Bacillus amyloliquefaciens SP1 was isolated from apple rhizosphere having multifarious plant growth promoting activities. Strain SP1 was purified to 6.48-fold using four-step purification protocol and characterized in detail for its robustness and ecofriendly application in leather and detergent industries. Structural analysis revealed that the protease was monomeric and had a molecular weight of 43 kDa. It exhibited optimum activity at 60 degrees C in alkaline environment (pH 8.0) and stable in the presence of surfactants and oxidizing agents. Enzyme was thermostable at 50 degrees C and retained more than 70% activity after 30 min incubation. It has shown stain removal property and dehairing of goat skin without chemical assistance and hydrolyzing fibrous proteins. This protease showed Km of 0.125 mg ml(-1) and V(max) of 12820 MUg ml(-1) indicating its excellent affinity and catalytic role. Thermal inactivation of the pure enzyme followed first-order kinetics. The half life of the pure enzyme at 50, 60, and 65 degrees C was 77, 19.80, and 13.33 min, respectively. The activation energy was 37.19 KJ mol(-1). The results suggest that the B. amyloliquefaciens SP1 has a potential application in different industries. PMID- 26375165 TI - Enhanced Electron Lifetimes in Dye-Sensitized Solar Cells Using a Dichromophoric Porphyrin: The Utility of Intermolecular Forces. AB - Electron lifetimes in dye-sensitized solar cells employing a porphyrin dye, an organic dye, a 1:1 mixture of the two dyes, and a dichromophoric dye design consisting of the two dyes using a nonconjugated linker were measured, suggesting that the dispersion force of the organic dyes has a significant detrimental effect on the electron lifetime and that the dichromophoric design can be utilized to control the effect of the dispersion force. PMID- 26375164 TI - Systematic Review of Brain Tumor Treatment in Dogs. AB - Intracranial neoplasia is commonly diagnosed in dogs and can be treated by a variety of methods, but formal comparisons of treatment efficacy are currently unavailable. This review was undertaken to summarize the current state of knowledge regarding outcome after the treatment of intracranial masses in dogs, with the aim of defining optimal recommendations for owners. This review summarizes data from 794 cases in 22 previously published reports and follows PRISMA guidelines for systematic review. A Pubmed search was used to identify suitable articles. These then were analyzed for quality and interstudy variability of inclusion and exclusion criteria and the outcome data extracted for summary in graphs and tables. There was a high degree of heterogeneity among studies with respect to inclusion and exclusion criteria, definition of survival periods, and cases lost to follow-up making comparisons among modalities troublesome. There is a need for standardized design and reporting of outcomes of treatment for brain tumors in dogs. The available data do not support lomustine as an effective treatment, but also do not show a clear difference in outcome between radiotherapy and surgery for those cases in which the choice is available. PMID- 26375166 TI - Growth Attenuation of Cutaneous Angiosarcoma With Propranolol-Mediated beta Blockade. AB - IMPORTANCE: Patients with stage T2 multilesion angiosarcomas of the scalp and face that are larger than 10 cm demonstrate a 2-year survival rate of 0%. To our knowledge, major therapeutic advances against this disease have not been reported for decades. Preclinical data indicate that blocking beta-adrenergic signaling with propranolol hydrochloride disrupts angiosarcoma cell survival and xenograft angiosarcoma progression. OBSERVATIONS: A patient presented with a beta adrenergic-positive multifocal stage T2 cutaneous angiosarcoma (>=20 cm) involving 80% of the scalp, left forehead, and left cheek, with no evidence of metastasis. The patient was immediately administered propranolol hydrochloride, 40 mg twice a day, as his workup progressed and treatment options were elucidated. Evaluation of the proliferative index of the tumor before and after only 1 week of propranolol monotherapy revealed a reduction in the proliferative index of the tumor by approximately 34%. A combination of propranolol hydrochloride, 40 mg 3 times a day, paclitaxel poliglumex, 2 mg/m2 infused weekly, and radiotherapy during the subsequent 8 months resulted in extensive tumor regression with no detectable metastases. CONCLUSIONS AND RELEVANCE: Our data suggest that beta-blockade alone substantially reduced angiosarcoma proliferation and, in combination with standard therapy, is effective for reducing the size of the tumor and preventing metastases. If successful, beta blockade could be the first major advancement in the treatment of angiosarcoma in decades. PMID- 26375167 TI - Efficient Transfer Doping of Carbon Nanotube Forests by MoO3. AB - We dope nanotube forests using evaporated MoO3 and observe the forest resistivity to decrease by 2 orders of magnitude, reaching values as low as ~5 * 10(-5) Omegacm, thus approaching that of copper. Using in situ photoemission spectroscopy, we determine the minimum necessary MoO3 thickness to dope a forest and study the underlying doping mechanism. Homogenous coating and tube compaction emerge as key factors for decreasing the forest resistivity. When all nanotubes are fully coated with MoO3 and packed, conduction channels are created both inside the nanotubes and on the outside oxide layer. This is supported by density functional theory calculations, which show a shift of the Fermi energy of the nanotubes and the conversion of the oxide into a layer of metallic character. MoO3 doping removes the need for chirality control during nanotube growth and represents a step forward toward the use of forests in next-generation electronics and in power cables or conductive polymers. PMID- 26375168 TI - Call for Organized Statewide Networks for Management of Acute Myocardial Infarction-Related Cardiogenic Shock. PMID- 26375169 TI - The Half RR Rule: A Poor Rule of Thumb and Not a Risk Assessment Tool for QT Interval Prolongation. AB - OBJECTIVES: Measuring the QT interval on an electrocardiogram (ECG) is integral to risk assessment of Torsade de Pointes (TdP). This study aimed to investigate the accuracy of the 1/2 RR rule as a risk assessment tool for drug-induced TdP, comparing it to the QT nomogram, Bazett's corrected QT (QTcB), and Fridericia's corrected QT (QTcF). METHODS: The authors calculated sensitivity and specificity of the 1/2 RR rule using a published data set of 129 cases of drug-induced TdP and 316 controls (noncardiotoxic overdoses), compared to the QT nomogram, QTcB > 500 msec and QTcF > 500 msec. To further determine the value of the 1/2 RR rule, its observed positive, and negative agreement were calculated when compared to the QT nomogram for determining an abnormal QT in eight samples of different drugs in overdose. RESULTS: The sensitivity and specificity of the 1/2 RR rule were 88% (95% confidence interval [CI] = 80% to 93%) and 53% (95% CI = 47% to 58%), respectively, compared to the QT nomogram (sensitivity = 97%, 95% CI = 92% to 99%; specificity = 99%, 95% CI = 97% to 100%). It was also less sensitive than QTcB > 500 msec and had a lower specificity than QTcB > 500 msec and QTcF > 500 msec. In drug overdose patients, the 1/2 RR rule had poor observed agreement averaging 41%, which was mainly due to poor positive agreement, except for amisulpride where there was good agreement. CONCLUSIONS: The 1/2 RR rule was not as sensitive as the QT nomogram or QTcB > 500 msec for drug-induced TdP. It had poor positive agreement in almost all overdose patients, resulting in over half of patients receiving unnecessary cardiac monitoring and repeat ECGs. PMID- 26375170 TI - Synthesis of Furo[3,2-c]benzopyrans via an Intramolecular [4 + 2] Cycloaddition Reaction of o-Quinonemethides. AB - An intramolecular [4 + 2] cycloaddition reaction of o-quinonemethides generated from salicylaldehydes and alpha-prenylated alcohols is described. In the presence of a catalytic amount of benzenesulfonic acid (BSA), the reaction proceeded smoothly in EtOH to afford furo[3,2-c]benzopyrans through a three-bond forming process in moderate to excellent yields with high diastereoselectivity. This reaction provides a simple and straightforward protocol to efficiently construct furo[3,2-c]benzopyran skeletons. A possible mechanism involving hemiacetal formation/hetero-Diels-Alder reaction is proposed to rationalize the observed results. PMID- 26375171 TI - Enhanced Wettability Changes by Synergistic Effect of Micro/Nanoimprinted Substrates and Grafted Thermoresponsive Polymer Brushes. AB - Thermoresponsive polymer brushes are grafted on micro/nanostructured polymer substrates as new intelligent interfaces that synergistically enhance wettability changes in response to external temperature stimuli. Thermoplastic poly(styrene co-4-vinylbenzyl chloride) [P(St-co-VBC)] is synthesized using radical polymerization and spin-coated on a glass substrate. Micro/nanopillar and hole patterns are imprinted on the P(St-co-VBC) layer using thermal nanoimprint lithography. Poly(N-isopropylacrylamide) (PIPAAm) brushes are grafted on the micro/nanostructured P(St-co-VBC) layer through surface-initiated atom-transfer radical polymerization using 4-vinylbenzyl chloride as the initiator. The imprinted micro/nanostructures and grafted PIPAAm brush chain lengths affect the surface wettability. Combinations of nanopillars or nanoholes (diameter 500 nm) and longer PIPAAm brushes enhance hydrophobic/hydrophilic changes in response to temperature changes, compared with the flat substrate. The thermoresponsive hydrophobic/hydrophilic transition is synergistically enhanced by the nanostructured surface changing from Cassie-Baxter to Wenzel states. This PIPAAm brush-modified micro/nanostructured P(St-co-VBC) is a new intelligent interface that effectively changes wettability in response to external temperature changes. PMID- 26375172 TI - Three-Dimensional Evaluation of Aortic Valve Annular Shape in Children With Bicuspid Aortic Valves and/or Aortic Coarctation Compared With Controls. AB - Bicuspid aortic valve (BAV) is the most common congenital cardiac abnormality, occurring in 1% to 2% of the general population. Adults with degenerative aortic valve (AV) disease have been shown to have an elliptical shaped AV annulus. The goal of this study was to investigate the shape of the aortic annulus in children with BAV, coarctation of the aorta (CoA) with or without BAV, and normal controls with trileaflet AVs using 3-dimensional echocardiography (3DE). We reviewed echocardiograms of children with isolated BAV (n = 40), CoA (n = 26), and controls (n = 40) that included 3DE of the AV. Eccentricity index (EI) was defined as the ratio between the smaller and larger annular dimension. DeltaD was defined as the difference between the larger and smaller annular dimension. Patients with BAV had an eccentric AV annulus compared with controls (BAV EI 0.85 +/- 0.05 and control EI 0.96 +/- 0.03; p <0.001). Subjects with CoA also had a more eccentric annulus than controls regardless of AV morphology (CoA 0.84 +/- 0.06; p <0.001). EI was not associated with somatic growth parameters or gender. Among all patients with BAV, AV dysfunction was associated with fusion of the right and noncoronary (R-N) cusps (p <0.001), but there was no association between valve dysfunction and EI. DeltaD was higher in both the BAV and CoA groups compared with the control group (BAV 3.4 +/- 1.9 mm, CoA 2.8 +/- 1.8 mm, and control 0.6 +/- 0.4 mm; p <0.001 each). Although there was no significant correlation of DeltaD with age in the control group during childhood, DeltaD increased with age in the BAV and CoA groups. In conclusion, children with BAV and/or CoA have an elliptical shaped AV annulus by 3DE, which is independent of age, gender, or body surface area. AV annular eccentricity may lead to inaccurate measurement of AV annular size if measured by 2DE alone. Considering AV annular eccentricity when balloon sizing the annulus before valvuloplasty may help improve interventional results in some patients. PMID- 26375173 TI - Clinical Research Abstracts of the British Equine Veterinary Association Congress 2015. AB - REASONS FOR PERFORMING STUDY: Colic is a common reason for owners to seek veterinary treatment for their working equids in Morocco. There is no information available regarding cultural, religious or educational barriers to obtaining treatment or about the typical workload of these animals which may predispose them to colic. OBJECTIVES: To characterise the typical workload and feeding regimens of working equids in Morocco; to characterise the ability of owners to recognise the clinical signs and causes of colic; and to identify specific barriers to the veterinary treatment of colic. STUDY DESIGN: Questionnaire-based survey. METHODS: A standardised, structured questionnaire was administered, with the assistance of an Arabic speaking interpreter, to the owners of working equids presenting their animals to 2 centres run by SPANA (The Society for the Protection of Animals Abroad). Participation was voluntary and informed consent was obtained prior to the interview. RESULTS: All of the 102 participants that completed questionnaire were male. Ninety-eight owners used their animals for pulling carts, with 12% of animals working 7 days per week. 14% of animals were offered water by their owner once per day and 2% every other day. 25% of animals were loose and allowed free to feed unsupervised when not working. 29% of owners were not able to name any cause of colic and 25% did not recognise any clinical signs; only 12% associated colic with gastrointestinal pain. 83% of owners would not seek veterinary treatment due to financial constraints if free treatment at SPANA centres were not available. CONCLUSIONS: Colic remains a common problem amongst working equids in Morocco. Improved knowledge of management factors associated with colic and how to recognise abdominal pain may reduce the incidence of colic and improve prognosis. The findings presented can be used to inform and develop owner education programmes. Ethical animal research: The study was reviewed and approved by the Ethics Committee, School of Veterinary Medicine and Science, University of Nottingham. Informed consent for participation in the study was obtained from all owners and was delivered in the native language. No details identifying the owner were recorded. SOURCE OF FUNDING: None. Competing interests: None declared. PMID- 26375174 TI - Regulation of neuronal pH by the metabotropic Zn(2+)-sensing Gq-coupled receptor, mZnR/GPR39. AB - Synaptically released Zn(2+) acts as a neurotransmitter, in part, by activating the postsynaptic metabotropic Zn(2+)-sensing Gq protein-coupled receptor (mZnR/GPR39). In previous work using epithelial cells, we described crosstalk between Zn(2+) signaling and changes in intracellular pH and/or extracellular pH (pHe). As pH changes accompany neuronal activity under physiological and pathological conditions, we tested whether Zn(2+) signaling is involved in regulation of neuronal pH. Here, we report that up-regulation of a major H(+) extrusion pathway, the Na(+)/H(+) exchanger (NHE), is induced by mZnR/GPR39 activation in an extracellular-regulated kinase 1/2-dependent manner in hippocampal neurons in vitro. We also observed that changes in pHe can modulate neuronal mZnR/GPR39-dependent signaling, resulting in reduced activity at pHe 8 or 6.5. Similarly, Zn(2+)-dependent extracellular-regulated kinase 1/2 phosphorylation and up-regulation of NHE activity were absent at acidic pHe. Thus, our results suggest that when pHe is maintained within the physiological range, mZnR/GPR39 activation can up-regulate NHE-dependent recovery from intracellular acidification. During acidosis, as pHe drops, mZnR/GPR39-dependent NHE activation is inhibited, thereby attenuating further H(+) extrusion. This mechanism may serve to protect neurons from excessive decreases in pHe. Thus, mZnR/GPR39 signaling provides a homeostatic adaptive process for regulation of intracellular and extracellular pH changes in the brain. We show that the postsynaptic metabotropic Zn(2+)-sensing Gq protein-coupled receptor (mZnR/GPR39) activation induces up-regulation of a major neuronal H(+) extrusion pathway, the Na(+)/H(+) exchanger (NHE), thereby enhancing neuronal recovery from intracellular acidification. Changes in extracellular pH (pHe), however, modulate neuronal mZnR/GPR39-dependent signaling, resulting in reduced activity at pHe 8 or 6.5. This mechanism may serve to protect neurons from excessive decreases in pHe during acidosis. Hence, mZnR/GPR39 signaling provides a homeostatic adaptive process for regulation of intracellular and extracellular pH changes in the brain. PMID- 26375175 TI - Clinical Research Abstracts of the British Equine Veterinary Association Congress 2015. AB - REASONS FOR PERFORMING STUDY: Infrared imaging is becoming popular as an aid to traditional diagnostic tools, its repeatability under practically relevant conditions is still discussed. OBJECTIVES: We hypothesise that time of day, ambient temperature and relative humidity affect thermography readings, and that there is no difference between values from left and right side. STUDY DESIGN: Repeated thermography in a convenience sample. METHODS: Fifteen sound horses were thermographically imaged at 3 time points in the same day (08.00, 12.00 and 16.00 h). Images were taken of the following regions: neck, carpus, distolateral thoracic limbs (cranial and tendon areas), thoracolumbar, pelvis, hock and pelvic limb tendons. Relative humidity and ambient temperature were recorded for each session. RESULTS: There was a significant difference between the temperature readings during the 3 imaging sessions in all areas (Friedman and Kruskal-Wallis; all P<0.014). Ambient temperature and relative humidity correlated with thermography readings in the caudal imaging areas (P<0.008 [temperature], P<0.032 [humidity]) of the horses, with an exception of one hock reading, but not in all cranial areas (P<0.365 [temperature], P<0.992 [humidity]) (Spearman's Rho). All but 2 regions (minimum values in the carpus and thoracic tendon areas in the morning session, (P = 0.033, 0.034) did not show significant difference between left and right sides at the same time of day (all P>0.057). CONCLUSIONS: Time of day, ambient temperature and relative humidity must be considered when using infrared imaging. Variations between the left and right sides of the horse can occur and should be considered during the analysis of pathological asymmetry. Ethical animal research: Ethical approval was granted from the Royal Veterinary College Ethics and Welfare committee as part of the first and second author's final year research project. SOURCE OF FUNDING: Funding was provided by the Royal Veterinary College as part of the first and second authors' final year research project. Competing interests: None declared. PMID- 26375176 TI - Acid Resistance and Molecular Characterization of Escherichia coli O157:H7 and Different Non-O157 Shiga Toxin-Producing E. coli Serogroups. AB - The objective of this study was to compare the acid resistance (AR) of non-O157 Shiga toxin-producing Escherichia coli (STEC) strains belonging to serogroups O26, O45, O103, O104, O111, O121, and O145 with O157:H7 STEC isolated from various sources in 400 mM acetic acid solutions (AAS) at pH 3.2 and 30 degrees C for 25 min with or without glutamic acid. Furthermore, the molecular subgrouping of the STEC strains was analyzed with the repetitive sequence-based PCR (rep-PCR) method using a DiversiLab(TM) system. Results for a total of 52 strains ranged from 0.31 to 5.45 log reduction CFU/mL in the absence of glutamic acid and 0.02 to 0.33 CFU/mL in the presence of glutamic acid except for B447 (O26:H11), B452 (O45:H2), and B466 (O104:H4) strains. Strains belonging to serogroups O111, O121, and O103 showed higher AR than serotype O157:H7 strains in the absence of glutamic acid. All STEC O157:H7 strains exhibited a comparable DNA pattern with more than 95% similarity in the rep-PCR results, as did the strains belonging to serogroups O111 and O121. Surprisingly, the DNA pattern of B458 (O103:H2) was similar to that of O157:H7 strains with 82% similarity, and strain B458 strain showed the highest AR to AAS among the O103 strains with 0.44 log reduction CFU/mL without glutamic acid. In conclusion, STEC serotypes isolated from different sources exhibited diverse AR and genetic subtyping patterns. Results indicated that some non-O157 STEC strains may have higher AR than STEC O157:H7 strains under specific acidic conditions, and the addition of glutamic acid provided enhanced protection against exposure to AAS. PMID- 26375177 TI - Fertility After Treatment With High Dose Melphalan in Women With Acute Myelogenous Leukemia. AB - BACKGROUND: High-dose melphalan (HDM) is an integral component of conditioning regimens for autologous and allogeneic hematopoietic stem cell transplantation for patients with malignant and non-malignant diseases. The gonadotoxic effects of HDM are often obscured by previous or concurrent administration of alkylating agents. From April 1996 to January 2006 our acute myeloid leukemia treatment regimen included induction and consolidation therapy with cytosine arabinoside, anthracyclines and etoposide, followed by HDM and autologous stem cell infusion. We explored gonadal function in surviving female patients so treated, who represent a unique group of patients exposed to HDM as a single gonadotoxic agent. PROCEDURE: The fertility assessment included a questionnaire, blood tests for luteinizing hormone, follicle stimulating hormone and anti mullerian hormone (AMH), and a gynecological ultrasound exam for antral follicular count (AFC). RESULTS: Eight female survivors participated. Although fertility assessment showed considerable damage to ovarian reserve in all participants, four of the eight female survivors conceived and bore children without medical intervention. CONCLUSION: In this cohort, HDM treatment reduced fertility potential but did not preclude fecundity. Early referral to a fertility clinic and long term follow-up including serial measurements of AMH levels and AFC for female patients receiving HDM are recommended. PMID- 26375178 TI - Clinical Research Abstracts of the British Equine Veterinary Association Congress 2015. AB - REASONS FOR PERFORMING STUDY: Triamcinolone is commonly used in equine practice for the treatment of orthopaedic conditions. A serious potential adverse effect of triamcinolone is laminitis. However, evidence for the risk of laminitis associated with triamcinolone use is limited. OBJECTIVES: To determine the risk of laminitis within 90 days of triamcinolone administration and compare with the risk of laminitis in a veterinary-attended horse population. STUDY DESIGN: Retrospective study of clinical records. METHODS: Text mining and data extraction was performed using content analysis software (SimStat-WordStat v.6) on a database of anonymous digital clinical records from a convenience sample of North American equine practices (n = 9). Medical records were retrieved using a dictionary of keywords for 3 groups of horses: 1) treated with triamcinolone, 2) age and practice matched control population (no triamcinolone) and 3) all laminitic horses. Records of horses within Groups 1 and 2 were mined for evidence of laminitis within a 90-day period of treatment or a random date respectively. Data manipulation and analysis was performed using R v3.0.0 (R Development Core Team). The prevalence of laminitis within all groups was determined and relative risk of developing laminitis determined by single logistic regression. RESULTS: The clinical records of 225,777 horses were examined. Overall prevalence of laminitis within the database was 1.1% (n = 2533). Triamcinolone was administered to 12.4% (n = 27,898) horses and 0.07% of treated horses (n = 20) developed laminitis. In the control population (n = 56,695), 0.2% of horses (n = 134) developed laminitis. The risk of developing laminitis was significantly lower in the triamcinolone treatment group than the control population (OR 0.3 95%CI, 0.18 0.48 P<0.001). CONCLUSIONS: Triamcinolone treatment does not increase the overall risk of a horse developing laminitis. However, further investigation of risk factors for laminitis in the 20 horses identified by this preliminary study is warranted to aid development of evidence-based treatment guidelines. Ethical animal research: This study was approved by the Ethics and Welfare Committee of the School of Veterinary Medicine at the University of Glasgow. Owners gave informed consent for their horses' inclusion in the study. Sources of funding: John Crawford Endowment Fund, University of Glasgow. Competing interests: None declared. PMID- 26375180 TI - [In Process Citation]. PMID- 26375179 TI - Cutting the Gordian Knot: Identifiability of anaplerotic reactions in Corynebacterium glutamicum by means of (13) C-metabolic flux analysis. AB - Corynebacterium glutamicum is the major workhorse for the microbial production of several amino and organic acids. As long as these derive from tricarboxylic acid cycle intermediates, the activity of anaplerotic reactions is pivotal for a high biosynthetic yield. To determine single anaplerotic activities (13) C-Metabolic Flux Analysis ((13) C-MFA) has been extensively used for C. glutamicum, however with different network topologies, inconsistent or poorly determined anaplerotic reaction rates. Therefore, in this study we set out to investigate whether a focused isotopomer model of the anaplerotic node can at all admit a unique solution for all fluxes. By analyzing different scenarios of active anaplerotic reactions, we show in full generality that for C. glutamicum only certain anaplerotic deletion mutants allow to uniquely determine the anaplerotic fluxes from (13) C-isotopomer data. We stress that the result of this analysis for different assumptions on active enzymes is directly transferable to other compartment-free organisms. Our results demonstrate that there exist biologically relevant metabolic network topologies for which the flux distribution cannot be inferred by classical (13) C-MFA. PMID- 26375181 TI - [Changing structures--Integrating health]. AB - Changes in (municipal) structures for the improvement of health are often required but, in contrast to behavioural measures, less frequently implemented and scientifically evaluated. Results on this subject for Germany are scarce. In recent years, municipal prevention and health promotion programmes received new impetus from the expansion of the German "Early Assistance" initiative. Early assistance programmes to help children grow up healthy initiated municipal processes such as the establishment of networks between health services and youth welfare services, prevention chains and nationwide initiatives. This has moved issues such as equal opportunities for health into the centre of politically driven structural development efforts. Neighbourhood management groups and municipal round tables on prevention-specific topics etc. have been established throughout Germany. Regarding this structural development, 6 projects from the field of prevention research give a good indication as to how the structure of municipal concepts can be effectively implemented. PMID- 26375182 TI - Dasatinib therapy can result in significant pulmonary toxicity. PMID- 26375183 TI - Understanding and Manipulating Electrostatic Fields at the Protein-Protein Interface Using Vibrational Spectroscopy and Continuum Electrostatics Calculations. AB - Biological function emerges in large part from the interactions of biomacromolecules in the complex and dynamic environment of the living cell. For this reason, macromolecular interactions in biological systems are now a major focus of interest throughout the biochemical and biophysical communities. The affinity and specificity of macromolecular interactions are the result of both structural and electrostatic factors. Significant advances have been made in characterizing structural features of stable protein-protein interfaces through the techniques of modern structural biology, but much less is understood about how electrostatic factors promote and stabilize specific functional macromolecular interactions over all possible choices presented to a given molecule in a crowded environment. In this Feature Article, we describe how vibrational Stark effect (VSE) spectroscopy is being applied to measure electrostatic fields at protein-protein interfaces, focusing on measurements of guanosine triphosphate (GTP)-binding proteins of the Ras superfamily binding with structurally related but functionally distinct downstream effector proteins. In VSE spectroscopy, spectral shifts of a probe oscillator's energy are related directly to that probe's local electrostatic environment. By performing this experiment repeatedly throughout a protein-protein interface, an experimental map of measured electrostatic fields generated at that interface is determined. These data can be used to rationalize selective binding of similarly structured proteins in both in vitro and in vivo environments. Furthermore, these data can be used to compare to computational predictions of electrostatic fields to explore the level of simulation detail that is necessary to accurately predict our experimental findings. PMID- 26375184 TI - Nitric oxide and reactive oxygen species are required for systemic acquired resistance in plants. AB - Systemic acquired resistance (SAR) is a form of broad-spectrum disease resistance that is induced in response to primary infection and that protects uninfected portions of the plant against secondary infections by related or unrelated pathogens. SAR is associated with an increase in chemical signals that operate in a collective manner to confer protection against secondary infections. These include, the phytohormone salicylic acid (SA), glycerol-3-phosphate (G3P), azelaic acid (AzA) and more recently identified signals nitric oxide (NO) and reactive oxygen species (ROS). NO, ROS, AzA and G3P function in the same branch of the SAR pathway, and in parallel to the SA-regulated branch. NO and ROS function upstream of AzA/G3P and different reactive oxygen species functions in an additive manner to mediate chemical cleavage of the C9 double bond on C18 unsaturated fatty acids to generate AzA. The parallel and additive functioning of various chemical signals provides important new insights in the overlapping pathways leading to SAR. PMID- 26375185 TI - Embedded Performance Validity Measures with Postdeployment Veterans: Cross Validation and Efficiency with Multiple Measures. AB - Embedded validity measures support comprehensive assessment of performance validity. The purpose of this study was to evaluate the accuracy of individual embedded measures and to reduce them to the most efficient combination. The sample included 212 postdeployment veterans (average age = 35 years, average education = 14 years). Thirty embedded measures were initially identified as predictors of Green's Word Memory Test (WMT) and were derived from the California Verbal Learning Test-Second Edition (CVLT-II), Conners' Continuous Performance Test-Second Edition (CPT-II), Trail Making Test, Stroop, Wisconsin Card Sorting Test-64, the Wechsler Adult Intelligence Scale-Third Edition Letter-Number Sequencing, Rey Complex Figure Test (RCFT), Brief Visuospatial Memory Test Revised, and the Finger Tapping Test. Eight nonoverlapping measures with the highest area-under-the-curve (AUC) values were retained for entry into a logistic regression analysis. Embedded measure accuracy was also compared to cutoffs found in the existing literature. Twenty-one percent of the sample failed the WMT. Previously developed cutoffs for individual measures showed poor sensitivity (SN) in the current sample except for the CPT-II (Total Errors, SN = .41). The CVLT-II (Trials 1-5 Total) showed the best overall accuracy (AUC = .80). After redundant measures were statistically eliminated, the model included the RCFT (Recognition True Positives), CPT-II (Total Errors), and CVLT-II (Trials 1-5 Total) and increased overall accuracy compared with the CVLT-II alone (AUC = .87). The combination of just 3 measures from the CPT-II, CVLT-II, and RCFT was the most accurate/efficient in predicting WMT performance. PMID- 26375186 TI - Flipping the switch: regulating MTOC location. PMID- 26375187 TI - The Science, and Art, of Program Dissemination: Strategies, Successes, and Challenges. AB - The purpose of this special issue is to provide readers with a greater awareness of the processes involved in dissemination, as well as existing supports that help disseminate and sustain evidence-based interventions. Although dissemination research is limited in most disciplines, it is particularly lacking in the social science field. Many interventions aimed to help children and adolescents are found to be efficacious every year, but program developers are often not equipped to understand how to scale up a program or sustain it after the initial funding. Consumers (e.g., service providers, who are consumers of interventions), on the other hand, often do not understand all that goes into implementing and scaling up an intervention. This special issue will: (a) introduce readers to the problem; (b) discuss some of the challenges with disseminating programs; and (c) present various existing supports that can help scale up and sustain interventions. PMID- 26375188 TI - From Evidence to Impact: Recommendations for a Dissemination Support System. AB - While finding effective solutions to child and adolescent health problems is very much a scientific endeavor, getting those solutions into widespread practice largely is not. This paper applies lessons from business and engineering to highlight the shortcomings of current approaches to science translation. In challenging the status quo, the paper introduces and defends three propositions: that many evidence-based programs are not worth disseminating; most research tested versions of programs are not ready for widespread use; and most intervention developers and testers make poor disseminators. These propositions provide the basis for recommending three components of an enhanced dissemination support system, and the conceptualization of a new model to disseminate evidence based solutions to promote child and adolescent health. PMID- 26375190 TI - Who Supports the Successful Implementation and Sustainability of Evidence-Based Practices? Defining and Understanding the Roles of Intermediary and Purveyor Organizations. AB - Research on implementation science has increased significantly over the past decade. In particular, psychologists have looked closely at the value and importance of bridging the gap between science and practice. As evidence-based practices (EBPs) become more prevalent, concrete mechanisms are needed to bring these scientifically supported treatments and interventions to community-based settings. Intermediary and purveyor organizations (IPOs) have emerged in recent years that specialize in bringing research to practice. Using a framework developed by Franks (), this descriptive study surveyed respondents that self identified as IPOs and focused on identifying shared definitions, functions, and activities. Results indicated that seven descriptive roles previously identified were supported by this survey and many common shared activities, goals, and functions across these organizations were observed. Further, these organizations appear to be influenced by the growing field of implementation science. Limitations and implications of this study are discussed. PMID- 26375189 TI - Three Cs of Translating Evidence-Based Programs for Youth and Families to Practice Settings. AB - Despite the growing number of evidence-based programs (EBPs) for youth and families, few are well-integrated in service systems or widely adopted by communities. One set of challenges to widespread adoption of EBPs relates to the transfer of programs from research and development to practice settings. This is often because program developers have limited guidance on how to prepare their programs for broad dissemination in practice settings. We describe Three Cs of Translation, which are key areas that are essential for developers to translate their EBPs from research to practice settings: (1) Communicate the underlying theory in terms easily understandable to end users, (2) Clarify fidelity and flexibility, and (3) Codify implementation lessons and examples. Program developers are in the best position to describe their interventions, to define intervention core components, to clarify fidelity and flexibility, and to codify implementation lessons from intervention studies. We note several advantages for developers to apply the Three Cs prior to intervention dissemination and provide specific recommendations for translation. PMID- 26375191 TI - Family Connections: Using Collaborative Partnerships to Support Dissemination. AB - Spreading and sustaining evidence-informed practice in child welfare is complex. In particular, putting in place an active dissemination strategy requires the recognition of these unique challenges. The purpose of this paper is to illustrate how collaborative partnerships between individuals and organizations may represent an opportunity for more widely disseminating evidence-based practice in child welfare. The benefit of collaborative partnerships has been established as a beneficial mechanism to spread evidence-supported protocols in medicine and has been experimented with through Breakthrough Series Collaboratives in child welfare. Interagency collaborative teams to lead dissemination of evidence-informed practice in child welfare are now beginning to be examined as a method to scale-up practices more quickly. This article will use Family Connections, a multifaceted, community-based service program that works with families to help them meet the basic needs of their children and prevent child maltreatment as a case study for how collaborative partnerships can aid in dissemination. PMID- 26375192 TI - Federal Mechanisms to Support Intervention Dissemination. AB - This paper examines federal mechanisms that support program developers and researchers in disseminating effective interventions for public benefit. The purpose of this paper is not to discuss the dissemination of intervention research (i.e., how to inform stakeholders about research findings), nor is it intended to discuss the research of intervention dissemination (i.e., what is the best approach to disseminate an intervention). Rather, the paper discusses the challenges specific to finding pathways to disseminate an intervention and describes federal opportunities to support intervention dissemination. Three specific mechanisms are discussed: Federal Registries of Evidence-Based Programs, the Tiered Evidence Grant Programs, and the Small Business Innovative Research (SBIR) and the Small Technology Transfer Research (STTR) programs. The article presents some limitations associated with federal mechanisms for dissemination of effective interventions, but is intended to highlight current and future opportunities they may offer. PMID- 26375193 TI - Bringing The Incredible Years(r) Programs to Scale. AB - The Incredible Years((r)) (IY) program series is a set of interlocking and comprehensive training programs for parents, teachers, and children. This article briefly reviews the theoretical foundations, goals, and research underlying these programs. The main purpose of the paper is to describe how the IY programs have been scaled up slowly and carefully with fidelity by engaging in a collaborative building project with strong links between the developer, agency or school administrator, mentors, coaches, clinicians, and families using eight foundational building blocks or fidelity tools. PMID- 26375194 TI - Item response analysis of a shortened German version of the morningness eveningness scale. AB - A shortened version of the German adaptation of the morningness-eveningness scale of Horne and Ostberg is analysed within a large sample of 994 physicians with respect to dimensionality, reliability, gender differences and validity. The psychometric analysis - which incorporates a highly robust method to check for unidimensionality - shows discrepancies towards unidimensionality and highlights three misfitting items. In addition, hypothesis testing indicates the presence of differential item functioning (DIF) with respect to gender which could be caused by differences in response formats. Although, reliability estimates are satisfactory, an overall lack of adequate psychometric properties of the scale within the population of physicians has to be reported. We derive suggestions for improvement of the original morningness-eveningness questionnaire (MEQ)-scale and provide general comments on how to check for unidimensionality without imposing a restrictive response model. PMID- 26375195 TI - Modeling sustainable reuse of nitrogen-laden wastewater by poplar. AB - Numerical modeling was used to simulate the leaching of nitrogen (N) to groundwater as a consequence of irrigating food processing wastewater onto grass and poplar under various management scenarios. Under current management practices for a large food processor, a simulated annual N loading of 540 kg ha(-1) yielded 93 kg ha(-1) of N leaching for grass and no N leaching for poplar during the growing season. Increasing the annual growing season N loading to approximately 1,550 kg ha(-1) for poplar only, using "weekly", "daily" and "calculated" irrigation scenarios, yielded N leaching of 17 kg ha(-1), 6 kg ha(-1), and 4 kg ha(-1), respectively. Constraining the simulated irrigation schedule by the current onsite wastewater storage capacity of approximately 757 megaliters (Ml) yielded N leaching of 146 kg ha(-1) yr(-1) while storage capacity scenarios of 3,024 and 4,536 Ml yielded N leaching of 65 and 13 kg ha(-1) yr(-1), respectively, for a loading of 1,550 kg ha(-1) yr(-1). Further constraining the model by the current wastewater storage volume and the available land area (approximately 1,000 hectares) required a "diverse" irrigation schedule that was predicted to leach a weighted average of 13 kg-N ha(-1) yr(-1) when dosed with 1,063 kg-N ha(-1) yr(-1). PMID- 26375196 TI - The effect of time constraints and running phases on combined event pistol shooting performance. AB - The combined event is a crucial aspect of the modern pentathlon competition, but little is known about how shooting performance changes through the event. This study aimed to identify (i) how performance-related variables changed within each shooting series and (ii) how performance-related variables changed between each shooting series. Seventeen modern pentathletes completed combined event trials. An optoelectronic shooting system recorded score and pistol movement, and force platforms recorded centre of pressure movement 1 s prior to every shot. Heart rate and blood lactate values were recorded throughout the event. Whilst heart rate and blood lactate significantly increased between series (P < 0.05), there were no accompanying changes in the time period that participants spent aiming at the target, shot score, pistol movement or centre of pressure movement (P > 0.05). Thus, combined event shooting performance following each running phase appears similar to shooting performance following only 20 m of running. This finding has potential implications for the way in which modern pentathletes train for combined event shooting, and highlights the need for modern pentathletes to establish new methods with which to enhance shooting accuracy. PMID- 26375198 TI - Opioid Analgesics and Nicotine: More Than Blowing Smoke. AB - Practitioners are highly likely to encounter patients with concurrent use of nicotine products and opioid analgesics. Smokers present with more severe and extended chronic pain outcomes and have a higher frequency of prescription opioid use. Current tobacco smoking is a strong predictor of risk for nonmedical use of prescription opioids. Opioid and nicotinic-cholinergic neurotransmitter systems interact in important ways to modulate opioid and nicotine effects: dopamine release induced by nicotine is dependent on facilitation by the opioid system, and the nicotinic-acetylcholine system modulates self-administration of several classes of abused drugs-including opioids. Nicotine can serve as a prime for the use of other drugs, which in the case of the opioid system may be bidirectional. Opioids and compounds in tobacco, including nicotine, are metabolized by the cytochrome P450 enzyme system, but the metabolism of opioids and tobacco products can be complicated. Accordingly, drug interactions are possible but not always clear. Because of these issues, asking about nicotine use in patients taking opioids for pain is recommended. When assessing patient tobacco use, practitioners should also obtain information on products other than cigarettes, such as cigars, pipes, smokeless tobacco, and electronic nicotine delivery systems (ENDS, or e-cigarettes). There are multiple forms of behavioral therapy and pharmacotherapy available to assist patients with smoking cessation, and opioid agonist maintenance and pain clinics represent underutilized opportunities for nicotine intervention programs. PMID- 26375199 TI - What Social Bonds have the Greatest Influence on Patterns of Substance Use among Child-Welfare-Involved Youth? AB - Child-welfare-involved youth may lack protective social bonds that could reduce their risk of substance use. We investigated whether caregiver, school, or peer bonds predict distinct patterns of substance use among child-welfare-involved youth. The sample included 720 participants in the National Survey of Child and Adolescent Well-Being II. Latent class analysis (LCA) and the three-step approach to incorporate indicator variables onto the latent classes were used. We found the following classes: (1) severe polysubstance use; (2) moderate polysubstance use; and (3) low use. Youth bonded to primary caregivers were less likely to be severe polysubstance drug users, but caregiver bonds did not protect against moderate polysubstance use. School bonds protected against severe polysubstance and moderate polysubstance. Youth bonded to deviant peers were more likely to be in the severe polysubstance use and moderate polysubstance use classes. Interventions targeting child-welfare-involved youth need to account for social bonds' effect on substance use. PMID- 26375200 TI - Regulation of production of the blue pigment indigoidine by the pseudo gamma butyrolactone receptor FarR2 in Streptomyces lavendulae FRI-5. AB - The gamma-butyrolactone autoregulator signaling cascade is widely distributed among Streptomyces species as an important regulatory system of secondary metabolism. In Streptomyces lavendulae FRI-5, a gamma-butyrolactone autoregulator IM-2 and the IM-2 specific receptor FarA control production of the blue pigment indigoidine together with two types of antibiotics: d-cycloserine and the nucleoside antibiotics. Here, we demonstrated by in silico analysis that farR2 (a farA homologue), which is located in a cluster of regulatory genes including farA, belongs to the family of pseudoreceptor regulator genes, and that the expression of farR2 is controlled by the IM-2/FarA regulatory system. Disruption of farR2 resulted in delayed production of indigoidine and in transcriptional derepression of the clustered far regulatory genes. Moreover, FarR2 bound to the FarA-binding sequences in the promoter regions of the regulatory genes that were downregulated by FarR2. PMID- 26375201 TI - Contribution to catalysis of ornithine binding residues in ornithine N5 monooxygenase. AB - The SidA ornithine N5-monooxygenase from Aspergillus fumigatus is a flavin monooxygenase that catalyzes the NADPH-dependent hydroxylation of ornithine. Herein we report a mutagenesis study targeting four residues that contact ornithine in crystal structures of SidA: Lys107, Asn293, Asn323, and Ser469. Mutation of Lys107 to Ala abolishes activity as measured in steady-state oxygen consumption and ornithine hydroxylation assays, indicating that the ionic interaction of Lys107 with the carboxylate of ornithine is essential for catalysis. Mutation of Asn293, Asn323, or Ser469 individually to Ala results in >14-fold increases in Km values for ornithine. Asn323 to Ala also increases the rate constant for flavin reduction by NADPH by 18-fold. Asn323 is unique among the four ornithine binding residues in that it also interacts with NADPH by forming a hydrogen bond with the nicotinamide ribose. The crystal structure of N323A complexed with NADP(+) and ornithine shows that the nicontinamide riboside group of NADP is disordered. This result suggests that the increase in flavin reduction rate results from an increase in conformational space available to the enzyme-bound NADP(H). Asn323 thus facilitates ornithine binding at the expense of hindering flavin reduction, which demonstrates the delicate balance that exists within protein-ligand interaction networks in enzyme active sites. PMID- 26375197 TI - Use of Dried Capillary Blood Sampling for Islet Autoantibody Screening in Relatives: A Feasibility Study. AB - BACKGROUND: Islet autoantibody testing provides the basis for assessment of risk of progression to type 1 diabetes. We set out to determine the feasibility and acceptability of dried capillary blood spot-based screening to identify islet autoantibody-positive relatives potentially eligible for inclusion in prevention trials. MATERIALS AND METHODS: Dried blood spot (DBS) and venous samples were collected from 229 relatives participating in the TrialNet Pathway to Prevention Study. Both samples were tested for glutamic acid decarboxylase, islet antigen 2, and zinc transporter 8 autoantibodies, and venous samples were additionally tested for insulin autoantibodies and islet cell antibodies. We defined multiple autoantibody positive as two or more autoantibodies in venous serum and DBS screen positive if one or more autoantibodies were detected. Participant questionnaires compared the sample collection methods. RESULTS: Of 44 relatives who were multiple autoantibody positive in venous samples, 42 (95.5%) were DBS screen positive, and DBS accurately detected 145 of 147 autoantibody-negative relatives (98.6%). Capillary blood sampling was perceived as more painful than venous blood draw, but 60% of participants would prefer initial screening using home fingerstick with clinic visits only required if autoantibodies were found. CONCLUSIONS: Capillary blood sampling could facilitate screening for type 1 diabetes prevention studies. PMID- 26375202 TI - Epidemiologic analysis of the clinical features of Japanese patients with polymyositis and dermatomyositis. AB - OBJECTIVES: This study aimed to investigate the clinical characteristics of polymyositis/dermatomyositis (PM/DM) in Japan by analyzing data from the nationwide registration system. METHODS: The data of the registration system in 2009 were analyzed to investigate patient numbers, sex, clinical symptoms, therapies, complications, and prognosis of PM/DM. RESULTS: The total number of PM/DM cases was approximately 17,000, and the female/male sex ratio was 2.7:1. Almost all patients improved as a result of therapy, but many suffered from sequelae such as muscle weakness. CONCLUSIONS: The results characterize significant aspects of Japanese PM/DM patients. However, a further prospective survey is required to clarify the true epidemiology and natural history of PM/DM. PMID- 26375203 TI - Comparative plasma proteomic studies of pulmonary TiO2 nanoparticle exposure in rats using liquid chromatography tandem mass spectrometry. AB - Mounting evidence suggests that pulmonary exposure to nanoparticles (NPs) has a toxic effect on biological systems. A number of studies have shown that exposure to NPs result in systemic inflammatory response, oxidative stress, and leukocyte adhesion. However, significant knowledge gaps exist for understanding the key molecular mechanisms responsible for altered microvasculature function. Utilizing comprehensive LC-MS/MS and comparative proteomic analysis strategies, important proteins related to TiO2 NP exposure in rat plasma have been identified. Molecular pathway analysis of these proteins revealed 13 canonical pathways as being significant (p <= 0.05), but none were found to be significantly up or down regulated (z>|2|). This work lays the foundation for future research that will monitor relative changes in protein abundance in plasma and tissue as a function of post-exposure time and TiO2 NP dosage to further elucidate mechanisms of pathway activation as well as to decipher other affected pathways. PMID- 26375204 TI - The intriguing heterogeneity of human salivary proline-rich proteins: Short title: Salivary proline-rich protein species. AB - The most heterogeneous family of human salivary proteins is represented by proline-rich proteins (PRPs) divided in acidic, basic, and basic glycosylated (aPRPs, bPRPs, gPRPs). They are encoded by six genes, clustered on chromosome 12p13.2: PRH1-2 encode aPRPs, PRB1-4 encode bPRPs and gPRPs. Each gene exists in different allelic forms: two for PRH2, three for PRH1, PRB2, and PRB4, four for PRB1, and PRB3. During granule maturation, PRP proproteins undergo proteolysis by the action of convertases and carboxypeptidases. Differently from bPRPs, proteolysis of aPRPs is not complete, and, besides fragments, entire protein species are also secreted. Maturation process generates ten aPRPs (PRP-1, PRP-2, PIF-s, Db-s, Pa, PRP-3, PRP-4, PIF-f, Db-f, P-C), and at least 18 bPRPs (II-2, P E, IB-6, Ps-1, Ps-2, IB-1, P-J, IB-8a, P-F, P-H, P-D, II-1, protein glycosylated A, CD-IIg, and Gl1-4). In addition, single nucleotide and length polymorphisms, and differentially spliced transcripts originate several natural variants. Phosphorylation, N-pyroglutaminylation, dimerization, and N-/O-glycosylation also occur during maturation, enlarging the number of protein species, further increased by proteolytic events governed by carboxy- and endo-peptidases during and after secretion, and giving rise to a huge number of small peptides. The PRP functional role is still poorly understood. SIGNIFICANCE: The high polymorphism of PRPs gives an important contribution to the high heterogeneity and inter individual variability of the human salivary proteome. The products of six genes clustered on chromosome 12p13.2 comprise a mixture of entire, truncated, phosphorylated, glycosylated and dimerized protein/peptide species, sharing large part of their sequences, and possibly involved in different biological activities. Whatever the role of PRP species is, it should be crucial, given that PRPs are the most conserved oral salivary proteins among mammals. PMID- 26375205 TI - Multi-objective optimization of chromatographic rare earth element separation. AB - The importance of rare earth elements in modern technological industry grows, and as a result the interest for developing separation processes increases. This work is a part of developing chromatography as a rare earth element processing method. Process optimization is an important step in process development, and there are several competing objectives that need to be considered in a chromatographic separation process. Most studies are limited to evaluating the two competing objectives productivity and yield, and studies of scenarios with tri-objective optimizations are scarce. Tri-objective optimizations are much needed when evaluating the chromatographic separation of rare earth elements due to the importance of product pool concentration along with productivity and yield as process objectives. In this work, a multi-objective optimization strategy considering productivity, yield and pool concentration is proposed. This was carried out in the frame of a model based optimization study on a batch chromatography separation of the rare earth elements samarium, europium and gadolinium. The findings from the multi-objective optimization were used to provide with a general strategy for achieving desirable operation points, resulting in a productivity ranging between 0.61 and 0.75 kgEu/mcolumn(3), h(-1) and a pool concentration between 0.52 and 0.79 kgEu/m(3), while maintaining a purity above 99% and never falling below an 80% yield for the main target component europium. PMID- 26375206 TI - The Cambridge Centre for Ageing and Neuroscience (Cam-CAN) data repository: Structural and functional MRI, MEG, and cognitive data from a cross-sectional adult lifespan sample. AB - This paper describes the data repository for the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) initial study cohort. The Cam-CAN Stage 2 repository contains multi-modal (MRI, MEG, and cognitive-behavioural) data from a large (approximately N=700), cross-sectional adult lifespan (18-87years old) population based sample. The study is designed to characterise age-related changes in cognition and brain structure and function, and to uncover the neurocognitive mechanisms that support healthy cognitive ageing. The database contains raw and preprocessed structural MRI, functional MRI (active tasks and resting state), and MEG data (active tasks and resting state), as well as derived scores from cognitive behavioural experiments spanning five broad domains (attention, emotion, action, language, and memory), and demographic and neuropsychological data. The dataset thus provides a depth of neurocognitive phenotyping that is currently unparalleled, enabling integrative analyses of age-related changes in brain structure, brain function, and cognition, and providing a testbed for novel analyses of multi-modal neuroimaging data. PMID- 26375207 TI - Characterisation and imaging of cortical impedance changes during interictal and ictal activity in the anaesthetised rat. AB - Epilepsy affects approximately 50 million people worldwide, and 20-30% of these cases are refractory to antiepileptic drugs. Many patients with intractable epilepsy can benefit from surgical resection of the tissue generating the seizures; however, difficulty in precisely localising seizure foci has limited the number of patients undergoing surgery as well as potentially lowered its effectiveness. Here we demonstrate a novel imaging method for monitoring rapid changes in cerebral tissue impedance occurring during interictal and ictal activity, and show that it can reveal the propagation of pathological activity in the cortex. Cortical impedance was recorded simultaneously to ECoG using a 30 contact electrode mat placed on the exposed cortex of anaesthetised rats, in which interictal spikes (IISs) and seizures were induced by cortical injection of 4-aminopyridine (4-AP), picrotoxin or penicillin. We characterised the tissue impedance responses during IISs and seizures, and imaged these responses in the cortex using Electrical Impedance Tomography (EIT). We found a fast, transient drop in impedance occurring as early as 12ms prior to the IISs, followed by a steep rise in impedance within ~120ms of the IIS. EIT images of these impedance changes showed that they were co-localised and centred at a depth of 1mm in the cortex, and that they closely followed the activity propagation observed in the surface ECoG signals. The fast, pre-IIS impedance drop most likely reflects synchronised depolarisation in a localised network of neurons, and the post-IIS impedance increase reflects the subsequent shrinkage of extracellular space caused by the intense activity. EIT could also be used to picture a steady rise in tissue impedance during seizure activity, which has been previously described. Thus, our results demonstrate that EIT can detect and localise different physiological changes during interictal and ictal activity and, in conjunction with ECoG, may in future improve the localisation of seizure foci in the clinical setting. PMID- 26375210 TI - Neural correlates of reflection on actual versus ideal self-discrepancy. AB - Subjective feelings of actual/ideal self-discrepancy vary across individuals and influence one's own affective states. However, the neural correlates of actual/ideal self-discrepancy and their genetic individual differences remain unknown. We investigated neural correlates of actual/ideal self-discrepancy and their associations with the serotonin transporter promoter polymorphism (5 HTTLPR) that moderates human affective states during self-reflection. We scanned short/short and long/long allele carriers of 5-HTTLPR, using functional MRI, during reflection on the distance between actual and ideal self in personality traits. We found that larger actual/ideal self-discrepancy was associated with activations in the ventral/dorsal striatum and dorsal medial and lateral prefrontal cortices. Moreover, these brain activities were stronger in short/short than long/long allele carriers and predicted self-report of life satisfaction in short/short carriers but trait depression in long/long carriers. Our findings revealed neural substrates of actual/ideal self-discrepancy and their associations with affective states that are sensitive to individuals' genetic makeup. PMID- 26375208 TI - Changes in white matter microstructure in the developing brain--A longitudinal diffusion tensor imaging study of children from 4 to 11years of age. AB - The purpose of the present study was to detail the childhood developmental course of different white matter (WM) characteristics. In a longitudinal diffusion tensor imaging (DTI) study of 159 healthy children between 4 and 11years scanned twice, we used tract-based spatial statistics as well as delineation of 15 major WM tracts to characterize the regional pattern of change in fractional anisotropy (FA), mean (MD), radial (RD) and axial diffusivity (AD). We tested whether there were decelerations of change with increasing age globally and tract-wise, and also illustrated change along medial-to-lateral, posterior-to-anterior and inferior-to-superior gradients. We found a significant linear increase in global FA, and decrease in MD and RD over time. For mean AD, a weak decrease was observed. The developmental changes in specific WM tracts showed regional differences. Eight WM tracts showed non-linear development patterns for one or several DTI metrics, with a deceleration in change with age. Sex did not affect change in any DTI metric. Overall, greater rate of change was found in the left hemisphere. Spatially, there was a posterior-to-anterior gradient of change with greater change in frontal regions for all metrics. The current study provides a comprehensive characterization of the regional patters of change in WM microstructure across pre-adolescence childhood. PMID- 26375211 TI - The integration of the internal and external milieu in the insula during dynamic emotional experiences. AB - Whilst external events trigger emotional responses, interoception (the perception of internal physiological states) is fundamental to core emotional experience. By combining high resolution functional neuroimaging with concurrent physiological recordings, we investigated the neural mechanisms of interoceptive integration during free listening to an emotionally salient audio film. We found that cardiac activity, a key interoceptive signal, was robustly synchronised across participants and centrally represented in the posterior insula. Effective connectivity analysis revealed that the anterior insula, specifically tuned to the emotionally salient moments of the audio stream, serves as an integration hub of interoceptive processing: interoceptive states represented in the posterior insula are integrated with exteroceptive representations by the anterior insula to highlight these emotionally salient moments. Our study for the first time demonstrates the insular hierarchy for interoceptive processing during natural emotional experience. These findings provide an ecologically-valid framework for elucidating the neural underpinnings of emotional deficits in neuropsychiatric disorders. PMID- 26375209 TI - A nested phosphorus and proton coil array for brain magnetic resonance imaging and spectroscopy. AB - A dual-nuclei radiofrequency coil array was constructed for phosphorus and proton magnetic resonance imaging and spectroscopy of the human brain at 7T. An eight channel transceive degenerate birdcage phosphorus module was implemented to provide whole-brain coverage and significant sensitivity improvement over a standard dual-tuned loop coil. A nested eight-channel proton module provided adequate sensitivity for anatomical localization without substantially sacrificing performance on the phosphorus module. The developed array enabled phosphorus spectroscopy, a saturation transfer technique to calculate the global creatine kinase forward reaction rate, and single-metabolite whole-brain imaging with 1.4cm nominal isotropic resolution in 15min (2.3cm actual resolution), while additionally enabling 1mm isotropic proton imaging. This study demonstrates that a multi-channel array can be utilized for phosphorus and proton applications with improved coverage and/or sensitivity over traditional single-channel coils. The efficient multi-channel coil array, time-efficient pulse sequences, and the enhanced signal strength available at ultra-high fields can be combined to allow volumetric assessment of the brain and could provide new insights into the underlying energy metabolism impairment in several neurodegenerative conditions, such as Alzheimer's and Parkinson's diseases, as well as mental disorders such as schizophrenia. PMID- 26375213 TI - Black women's hair: the main scalp dermatoses and aesthetic practices in women of African ethnicity. AB - Afro-ethnic hair is different from Caucasian and Asian hair and has unique features. Ethnic hair is more prone to certain conditions or diseases. Such diseases are not only related to the fragile inner structure of the hair, but also to the cultural habits of hairstyles that often exert traction forces upon the pilosebaceous follicle. Women with African hair subject their hair to chemical treatments such as hair straightening and relaxing, and thus modify the structure of their hair shaft, making it more susceptible to damage. For this reason, hair complaints are common among black women and represent a diagnostic challenge to the dermatologist, requiring a thorough clinical examination of the hair and scalp, and a detailed medical history of the patient. The purpose of this review is to warn of the potential side effects and sequelae related to hairstyles and hair treatments used by black women, and to highlight the major diseases that affect this ethnicity. PMID- 26375212 TI - Genes influence the amplitude and timing of brain hemodynamic responses. AB - In functional magnetic resonance imaging (fMRI), the hemodynamic response function (HRF) reflects regulation of regional cerebral blood flow in response to neuronal activation. The HRF varies significantly between individuals. This study investigated the genetic contribution to individual variation in HRF using fMRI data from 125 monozygotic (MZ) and 149 dizygotic (DZ) twin pairs. The resemblance in amplitude, latency, and duration of the HRF in six regions in the frontal and parietal lobes was compared between MZ and DZ twin pairs. Heritability was estimated using an ACE (Additive genetic, Common environmental, and unique Environmental factors) model. The genetic influence on the temporal profile and amplitude of HRF was moderate to strong (24%-51%). The HRF may be used in the genetic analysis of diseases with a cerebrovascular etiology. PMID- 26375214 TI - The association of fractional CO2 laser 10.600nm and photodynamic therapy in the treatment of onychomycosis. AB - BACKGROUND: Onychomycosis is a fungal infection of the nails caused in most cases by dermatophytes Trichophyton rubrum and Trichophyton mentagrophytes. Despite numerous available antifungal drugs for therapy of this infection, the cure rate is low, with high rates of relapse after treatment and side effects. OBJECTIVES: To present a new option for the treatment of onychomycosis, in search of a more effective and rapid method than conventional ones. METHODS: Patients underwent two sessions of CO2 fractional laser 10.600nm associated with photodynamic therapy. Mycological and digital photography were performed before and after the treatment. RESULTS: McNemar test with continuity correction and degrees of freedom = 1: for clinical cure rate, 13.06, with p=0.00005; for mycological cure, 17.05, with p=0.00005; 72% felt fully satisfied with the procedure. CONCLUSIONS: The use of fractional CO2 laser 10.600nm associated with photodynamic therapy can be effective in the treatment of onychomycosis, decreasing the risk of systemic lesions that may be triggered with prolonged use of oral antifungals. PMID- 26375215 TI - Evaluation of 25 years of phototherapy for treating psoriasis at a teaching hospital in southern Spain. AB - BACKGROUND: For years, phototherapy has been used in a wide range of skin diseases, which is unsurprising as skin is the anatomical feature most directly exposed to light, especially in psoriasis. Although the role of light therapy has been replaced by different therapeutic modalities in recent years, this treatment is now an established option for many skin diseases. OBJECTIVES: The aim was to characterize the patient population that had received the aforementioned treatment in the Virgen Macarena Health Area in Seville (Spain) between June 1985 and October 2011. METHODS: We have designed a descriptive study with a univariate analysis covering 443 treatments with light therapy, all administered to the same number of patients suffering from psoriasis. RESULTS: 79.15% of patients were discharged due to improvement or healing, while the 20.85% were discharged due to other reasons. The average total accumulative dose was 131.53 J/cm2. We do not detected an increase in proportion in patients for develop NMSK after light therapy treatment. CONCLUSIONS: We consider that phototherapy is still an effective and efficient treatment that will have to be reconsidered in the current macroeconomic context. PMID- 26375216 TI - Oral isotretinoin in photoaging: objective histological evidence of efficacy and durability. AB - BACKGROUND: The off-label use of oral isotretinoin in photoaging is a therapeutic tool that has been used by dermatologists. There are few studies to corroborate its effectiveness and durability. OBJECTIVES: To assess, both clinically and histologically, the changes caused by the use of oral isotretinoin in skin photoaging as well as the duration of the effects. METHODS: 20 female patients, aged 45-50 years, with phototypes II-VI, none of whom had experienced menopause, were treated with 20mg oral isotretinoin, 3 days a week, for 12 weeks. They underwent clinical analysis and skin biopsies in the pre-auricular region, while histologic cuts enabled assessment of the solar elastosis level and morphologic analysis. RESULTS: Clinically, patients, as well as the researching and the assessor physicians, noticed improvement in skin quality. One patient presented severe solar elastosis, 11 manifested the moderate form, while 8 presented the discreet type. According to histological analysis, 65% of the patients revealed alteration in the distribution and thickness of the elastic fibers, which can be interpreted as a histological improvement, while 60% showed an increase in collagen density. We observed an increase in collagen density, from 51.2% to 57.4%, (p=0.004). At the end of the 12-week follow-up period, this density decreased to 54.7% (p=0.050). There was an increase in the density of elastic fibers, from 26.5% to 31.3%, (p=0.02), which had dropped to 27.5% at the end of the 12-week follow-up period. CONCLUSIONS: The study confirmed the role of oral isotretinoin in remodeling the extracellular matrix against photoaging, as well as its durability after 12 weeks, especially when we consider collagen fibers. PMID- 26375217 TI - Dermoscopic and clinical features of head and neck melanoma. AB - BACKGROUND: The dermoscopic criteria of extrafacial melanomas are well-known. OBJECTIVE: To determine the frequency of dermatoscopic findings in head and neck melanomas (HNM) and to assess the distinguishing dermoscopic criteria of facial and extrafacial melanoma. METHODS: This observational study included 108 patients with HNM (63% male, mean age 64 years). Participants underwent individual dermoscopic imaging of clinically melanoma. All lesions were excised, and histopathological examination was performed on all specimens. RESULTS: Drawing on histopathological analysis, lentigo maligna melanoma or lentigo maligna was diagnosed in 60 lesions, superficial spreading melanoma in 18, nodular in 10, desmoplastic in 8, superficial spreading melanoma in situ in 12. The most frequent location for head and neck melanoma was the cheek (60 patients, 55.6%). Eight prominent dermatoscopic features were observed in facial melanoma: annular granular pattern (18%); rhomboidal structures (29%); pseudonetwork (29%); asymmetrical, pigmented, follicular openings (51%); obliterated hair follicles (8%); red rhomboidal structures (18%); increased density of the vascular network (32%); scar-like depigmentation (59%). CONCLUSIONS: HNM has specific dermoscopic features, and classical extrafacial dermoscopic rules are less useful for diagnosis of facial melanoma. In our study, further characteristic dermatoscopic findings were detected in facial melanoma such as low frequencies of irregular dots, 2 or fewer colors in lesions, the presence of pseudonetwork, increased density of the vascular network, red rhomboidal structures, in addition to dermatoscopic findings of extrafacial melanoma. Thus, it is concluded that the prediction and identification of HNM may be evident with the help of these signs. PMID- 26375218 TI - Physiological and lifestyle factors contributing to risk and severity of peri orbital dark circles in the Brazilian population. AB - BACKGROUND: Peri-orbital dark circles are a cosmetic concern worldwide, and have been attributed to hyperpigmentation from allergy or atopic dermatitis, blood stasis, structural shadowing effects, and a thin epidermis/dermis under the eye. It is of interest to better understand lifestyle and demographic risk factors and the relative impact of melanin, blood and epidermal/dermal factors on the severity of Peri-orbital dark circles. OBJECTIVE: To compare by non-invasive imaging the impact of biological factors to a visual grading scale for Peri orbital dark circles, and test the correlation of various demographic factors with Peri-orbital dark circles. METHODS: Subjects completed a lifestyle and health survey, and Peri-orbital dark circles severity was evaluated using standardized photographs. Hyperspectral image analysis was used to assess the contributions of melanin, blood volume, degree of blood oxygen saturation, and dermal scattering. RESULTS: Family history was the most significant risk factor for Peri-orbital dark circles. The average age of onset was 24 years, and earlier onset correlated with higher severity scores. Asthma was significantly associated with Peri-orbital dark circles scores, but self-reported allergy was not. In this study, sleep was not correlated with Peri-orbital dark circles scores. Hyperspectral imaging indicated that melanin was the dominant correlate for Peri orbital dark circles severity, while oxygen saturation was secondary. The difference between under-eye and cheek measurements for DeltaL*and DeltaE* were the most significant instrumental parameters correlated with visual assessment of Peri-orbital dark circles severity. CONCLUSION: Although typically associated with lack of sleep, risk of Peri-orbital dark circles is primarily hereditary. The main factors contributing to the appearance of Peri-orbital dark circles are melanin and (deoxygenated) blood. PMID- 26375219 TI - Clinicopathological profile and management of 161 cases of actinic cheilitis. AB - BACKGROUND: Actinic cheilitis (AC) is a potentially malignant disorder of the lip caused by chronic exposure to ultraviolet radiation from the sun. OBJECTIVES: To evaluate the clinical, demographic, morphological and therapeutic management in AC cases data associating to the histopathological grading. METHODS: Demographic, clinical and management data of 161 patients with AC were analyzed. In biopsied cases, two calibrated examiners performed histopathological grading by binary system. RESULTS: There was a prevalence of males (79.5%), aged 40 years or older (77.5%), light-skinned (85.7%), experiencing occupational exposure to sunlight (80.3%), with AC presenting clinically as white lesions (33.6%). Conservative treatment was adopted in 78 cases and biopsy in 83 cases (60.2% graded as low risk AC). There were no significant associations between histopathological grading and gender (p= 0.509), age (p=0.416), ethnicity (p=0.388), occupational exposure to sunlight (p=1.000) or clinical presentation (p=0.803). CONCLUSION: This study reinforces the hypothesis that demographic and clinical characteristics of AC are not related to histopathological grading. Advice on protection from sun exposure should be encouraged to avoid progression of AC and invasive therapies. PMID- 26375220 TI - Quality of life in patients with oculocutaneous albinism. AB - BACKGROUND: The social reality of the albino needs to be more studied in Brazil, as myths and social segregation regarding this illness are likely to be found in the country, with psychosocial and medical implications. OBJECTIVE: As this subject has not been referenced in previous scientific articles in Brazil, this research intends to evaluate the quality of life of the albinos that treated at our medical institution. METHODS: The quality of life was evaluated through the WHOQOL-BREF. Furthermore, two aspects of main relevance in the lives of the albinos were also objects of research, low vision and skin cancer. The sample consisted of forty oculocutaneous albinos and a control group of forty healthy individuals, matched by sex and age. RESULTS: Among the participants, 57.7% were between 18 and 40 years old, 28.2% were between 41 and 60, and 14.1% were over 60. 42.1% had skin cancer before the study, 18.4% had skin cancer during the study and 89.5% stated visual deficit. The results obtained in the questionnaires showed a statistically significant difference in the physical domain, with P < 0.001. CONCLUSION: Low vision combined with skin lesions and social stigma may contribute to disturbances in the quality of life of oculocutaneous albinos. The results presented in this study demonstrated the vulnerability of the affected individuals and the special care required by those patients, at the same time that the need for further research is highlighted in order to better elucidate the aspects related to albinism. PMID- 26375221 TI - Three different clinical faces of the same histopathological entity: hair follicle nevus, trichofolliculoma and accessory tragus. AB - BACKGROUND: Hair follicle nevus is a rare, congenital hamartoma with follicular differentiation characterized histologically by numerous, tiny, mature hair follicles. Trichofolliculoma, the histopathological features of which are quite similar to those of hair follicle nevus, is also a hamartoma that differs from hair follicle. Accessory tragus is a relatively common, benign congenital abnormality of the external ear with an incidence rate of 1 to 10 per 1,000 live births. OBJECTIVE: This study seeks to assess the discriminatory value of currently available, histological criteria in the differential diagnosis of hair follicle nevus, accessory tragi and trichofolliculoma. METHODS: Twenty-one patients comprising 9 cases of hair follicle nevus, 8 accessory tragi patients and 4 trichofolliculoma cases, were recruited to perform the study. RESULTS: There were 10 males and 11 females in the study group. No significant difference was observed between the three study groups in terms of age, gender or histopathological parameters such as density of hair follicles, subcutaneous fat score and presence of connective tissue framework. Cartilaginous component was seen in 8 cases that were diagnosed as accessory tragi, while central cyst and radiating hair follicles were seen in 4 cases which were diagnosed as trichofolliculoma. CONCLUSION: The results of our study showed that diagnostic discrimination of these diseases could be made only with the clinicopathologic correlation because of their clinical and histopathological similarities. PMID- 26375222 TI - Test of association: which one is the most appropriate for my study? AB - BACKGROUND: Hypothesis tests are statistical tools widely used for assessing whether or not there is an association between two or more variables. These tests provide a probability of the type 1 error (p-value), which is used to accept or reject the null study hypothesis. OBJECTIVE: To provide a practical guide to help researchers carefully select the most appropriate procedure to answer the research question. We discuss the logic of hypothesis testing and present the prerequisites of each procedure based on practical examples. PMID- 26375225 TI - Granulomatous mycosis fungoides--a diagnostic challenge. AB - Granulomatous mycosis fungoides is a rare subtype of T-cell cutaneous lymphoma. Due to its clinical heterogenicity the diagnosis is delayed and based on histopathological and immuno-histochemical findings, sometimes requiring gene rearrangement studies for confirmation. We report the case of a patient who was submitted to several biopsies before diagnostic conclusion. PMID- 26375223 TI - Female Pattern Hair Loss: a clinical and pathophysiological review. AB - Female Pattern Hair Loss or female androgenetic alopecia is the main cause of hair loss in adult women and has a major impact on patients' quality of life. It evolves from the progressive miniaturization of follicles that lead to a subsequent decrease of the hair density, leading to a non-scarring diffuse alopecia, with characteristic clinical, dermoscopic and histological patterns. In spite of the high frequency of the disease and the relevance of its psychological impact, its pathogenesis is not yet fully understood, being influenced by genetic, hormonal and environmental factors. In addition, response to treatment is variable. In this article, authors discuss the main clinical, epidemiological and pathophysiological aspects of female pattern hair loss. PMID- 26375224 TI - Vascular structures in dermoscopy. AB - Dermoscopy is an aiding method in the visualization of the epidermis and dermis. It is usually used to diagnose melanocytic lesions. In recent years, dermoscopy has increasingly been used to diagnose non-melanocytic lesions. Certain vascular structures, their patterns of arrangement and additional criteria may demonstrate lesion-specific characteristics. In this review, vascular structures and their arrangements are discussed separately in the light of conflicting views and an overview of recent literature. PMID- 26375226 TI - Acute generalized exanthematous pustulosis x Von Zumbusch's pustular psoriasis: a diagnostic challenge in a psoriatic patient. AB - Severe cutaneous drug reactions include a wide spectrum of clinical manifestations ranging from mild morbilliform cutaneous rash, to severe forms of hypersensitivity. Special attention is given in this report to the acute generalized exanthematous pustulosis (AGEP), induced in 90% of cases by the use of systemic drugs, especially aminopenicillins and macrolides. The incidence of the disease is low, 1-5 cases per million patients / year. The main differential diagnosis is Von Zumbusch's Pustular Psoriasis. The prognosis is generally good and the disease self limited, after withdrawal of the triggering drug. In this report the authors describe a case of AGEP, triggered by ceftriaxone in a patient with psoriasis vulgaris. PMID- 26375228 TI - Cutaneous metastasis from gastrointestinal adenocarcinoma of unknown primary origin. AB - Cutaneous metastasis is a rare manifestation of visceral malignancies that indicates primarily advanced disease. Due to its low incidence and similarity to other cutaneous lesions, it is not uncommon to have a delayed diagnosis and a shortened prognosis. We describe the case of a patient who presented with a cutaneous nodule in the sternal region as a first sign of malignancy. PMID- 26375227 TI - Erythema elevatum diutinum and hypothyroidism: coincidence or causal relationship? AB - Erythema elevatum diutinum is a rare chronic leukocytoclastic vasculitis of unknown etiology. It is believed to be due to deposition of immune complexes in the vessels. Clinically it is manifested as erythematous violaceous papules and nodules, isolated or confluent with hardened consistency, symmetrical, usually located on the extensor surface of the extremities, particularly over the joints. Diagnosis is based on clinical and histological findings. We report the case of a woman, 71 years old, with erythematous violaceous nodules on the hands, elbows, back and legs, beginning two years ago, with pain and itching. Histopathological analysis revealed leukocytoclastic vasculitis, confirming the clinical suspicion. Laboratory tests revealed hypothyroidism. We report the case because of its rarity, with subsequent review of the literature. PMID- 26375229 TI - Sweet Syndrome in childhood. AB - Sweet syndrome or acute febrile neutrophilic dermatosis is a recurrent and rare skin disease caused by the release of cytokines, with diverse possible etiologic causes. It presents clinically with polymorphic skin lesions, fever, arthralgia, and peripheral leukocytosis. In general, it is associated with infections, malignancy and drugs. It usually regresses spontaneously and treatment is primarily to control the basic disease. The authors report the case of a child of 1 year and 11 months who developed Sweet syndrome. PMID- 26375230 TI - Wells syndrome associated with chronic lymphocytic leukemia. AB - Eosinophilic cellulitis or Wells syndrome is an uncommon skin condition of unknown etiology that can occur alone or associated with other conditions. Typically, it presents with recurrent pruritic, erythematous and edematous plaques, but it can also show clinical polymorphism. Besides the cutaneous lesions, patients can experience systemic manifestations like fever, malaise, arthralgia and peripheral blood eosinophilia. We describe a case of this rare syndrome that presented with polymorphic cutaneous lesions associated with a serious systemic disease, which was revealed through the investigation of the cutaneous disease. PMID- 26375231 TI - Two friends with eroded nodules on the ears: atypical fibroxanthoma case report. AB - Atypical fibroxanthoma is an uncommon mesenchymal tumor that manifests clinically as a reddish papule or nodule in sun-exposed areas of the body. The clinical presentation is not specific and histology and immunohistochemistry are both necessary for a correct diagnosis. Surgery is the gold standard of therapy. Recurrence and metastasis should be excluded with a follow-up at 6 months, since this tumor should nowadays be considered a medium-grade neoplasm, rather than low grade as previously believed. We report the case of two friends who came to our hospital during the same period, complaining of very similar lesions. After biopsy and immunohistochemical examination, a diagnosis of atypical fibroxanthoma in both cases was formulated. PMID- 26375232 TI - Scanning electron microscopy of the collodion membrane from a self-healing collodion baby. AB - Self-healing collodion baby is a well-established subtype of this condition. We examined a male newborn, who was covered by a collodion membrane. The shed membrane was examined with scanning electron microscopy. The outer surface showed a very compact keratin without the normal elimination of corneocytes. The lateral view of the specimen revealed a very thick, horny layer. The inner surface showed the structure of lower corneocytes with polygonal contour. With higher magnifications villous projections were seen in the cell membrane. PMID- 26375233 TI - Jorge Lobo's disease. AB - Jorge Lobo's Disease is a rare, chronic granulomatous cutaneous mycosis, which is typical of tropical and subtropical regions. It is caused by the traumatic implantation of the fungus Lacazia loboi into the skin and subcutaneous tissue. The disease was first described in 1931 by Jorge Lobo, in Recife (PE), Brazil. It is common in Central and South America, and predominates in the Amazon region. We report a case of Jorge Lobo's Disease, which had been initially referred as being paracoccidioidomycosis. We emphasize clinical and diagnostic features of the disease. PMID- 26375234 TI - Syndrome in Question. AB - Waardenburg syndrome is an inherited disease characterized by sensorineural hearing loss, pigmentation changes and minor facial malformations. It has four clinical variants. We report the case of a girl who, like her mother, was affected by this syndrome. The diagnosis was made after detection and treatment of deafness. PMID- 26375236 TI - Ultraviolet radiation emitted by lamps, TVs, tablets and computers: are there risks for the population? AB - The frequent human exposure to various types of indoor lamps, as well as other light sources (television monitors, tablets and computers), raises a question: are there risks for the population? In the present study the emission of UVA and UVB radiation by lamps and screens of electronic devices were measured in order to determine the safe distance between the emitting source and the individual. We concluded that the lamps and electronic devices do not emit ultraviolet radiation; so they pose no health risk for the population. PMID- 26375235 TI - Is adermatoglyphia an additional feature of Kindler Syndrome? AB - A typical feature of Kindler Syndrome is skin fragility; this condition in currently classified as a form of epidermolysis bullosa. We describe a rarely reported feature of two cases, one sporadic and one familial; both patients noticed acquired adermatoglyphia. The loss of dermatoglyphics could be an additional feature of this syndrome. PMID- 26375237 TI - Trichophyton rubrum dermatophytosis in a patient under chronic use of systemic corticoids: an exuberant presentation. PMID- 26375238 TI - Systemic lupus erythematosus in a patient with Turner syndrome. PMID- 26375239 TI - Correction: Nevus sebaceo cerebriforme: uma rara apresentacao. AB - [This corrects the article DOI: 10.1590/abd1806-4841.20153433.]. PMID- 26375240 TI - Government, politics and health policy: A quantitative analysis of 30 European countries. AB - RATIONALE: Public health policies are often dependent on political decision making, but little is known of the impact of different forms of government on countries' health policies. In this exploratory study we studied the association between a wide range of process and outcome indicators of health policy and four groups of political factors (levels of democracy, e.g. voice and accountability; political representation, e.g. voter turnout; distribution of power, e.g. constraints on the executive; and quality of government, e.g. absence of corruption) in contemporary Europe. DATA AND METHODS: Data on 15 aspects of government and 18 indicators of health policy as well as on potential confounders were extracted from harmonized international data sources, covering 30 European countries and the years 1990-2010. In a first step, multivariate regression analysis was used to relate cumulative measures of government to indicators of health policy, and in a second step panel regression with country fixed effects was used to relate changes in selected measures of government to changes in indicators of health policy. RESULTS: In multivariate regression analyses, measures of quality of democracy and quality of government had many positive associations with process and outcome indicators of health policy, while measures of distribution of power and political representation had few and inconsistent associations. Associations for quality of democracy were robust against more extensive control for confounding variables, including tests in panel regressions with country fixed effects, but associations for quality of government were not. CONCLUSIONS: In this period in Europe, the predominant political influence on health policy has been the rise of levels of democracy in countries in the Central & Eastern part of the region. In contrast to other areas of public policy, health policy does not appear to be strongly influenced by institutional features of democracy determining the distribution of power, nor by aspects of political representation. The effect of quality of government on health policy warrants more study. PMID- 26375242 TI - Reply to "Debilitating fatigue as a treatment indication in chronic hepatitis C". PMID- 26375241 TI - Opposing effects of alcohol on the immune system. AB - Several studies have described a dose-dependent effect of alcohol on human health with light to moderate drinkers having a lower risk of all-cause mortality than abstainers, while heavy drinkers are at the highest risk. In the case of the immune system, moderate alcohol consumption is associated with reduced inflammation and improved responses to vaccination, while chronic heavy drinking is associated with a decreased frequency of lymphocytes and increased risk of both bacterial and viral infections. However, the mechanisms by which alcohol exerts a dose-dependent effect on the immune system remain poorly understood due to a lack of systematic studies that examine the effect of multiple doses and different time courses. This review will summarize our current understanding of the impact of moderate versus excessive alcohol consumption on the innate and adaptive branches of the immune system derived from both in vitro as well as in vivo studies carried out in humans and animal model studies. PMID- 26375243 TI - Reply to "Response assessment for HCC patients treated with repeated TACE: The optimal time-point is still an open issue". PMID- 26375244 TI - Reply to "Debilitating fatigue as a treatment indication in chronic hepatitis C". PMID- 26375245 TI - Pros and Cons: Usage of organs from donors infected with hepatitis C virus - Revision in the direct-acting antiviral era. AB - Should organs from hepatitis C antibody positive donors (HCVD+) be used for transplantation? Organ shortage forces transplant teams to use donors with extended criteria. The decision to transplant a HCVD+ graft is a balance between the risk of transmission of a virus that could lead to end-stage liver diseases and the benefit of access to transplantation, specifically in patients with life threatening disease. The other issue is the impact of HCV-related liver fibrosis in the donor graft on the long-term outcome in the recipient. Thus, the use of HCVD+ demonstrated a shorter meantime on the waiting list in kidney transplantation. When a HCVD+ graft is transplanted, the risk of HCV transmission depends on; 1) the quality of screening of the donor; 2) the presence of viral replication in the donor at the time of transplantation and the ability to detect it; and 3) the HCV status of the recipient but also the type of transplanted organ. In liver transplantation, the use of HCVD+ graft is usually restricted to recipients with a chronic HCV infection. Several reports showed some competition between HCV donor and recipient strain without deleterious impact on graft and patient survival. Controversies are still pending regarding the quality of the graft and the progression of fibrosis. The recent approval of direct-acting antiviral agents (DAA) dramatically changes the landscape of HCV infection treatment. After transplantation, combinations of DAA show high efficacy and good safety profile. In the near future, extensive use of DAA should reduce the number of HCVD+ with a positive HCV RNA, limiting the risk of transmission but also the number of patients on waiting lists for a disease related to HCV. PMID- 26375246 TI - Present and future of cervical cancer prevention in Spain: a cost-effectiveness analysis. AB - Human papillomavirus (HPV) vaccination within a nonorganized setting creates a poor cost-effectiveness scenario. However, framed within an organized screening including primary HPV DNA testing with lengthening intervals may provide the best health value for invested money. To compare the effectiveness and cost effectiveness of different cervical cancer (CC) prevention strategies, including current status and new proposed screening practices, to inform health decision makers in Spain, a Markov model was developed to simulate the natural history of HPV and CC. Outcomes included cases averted, life expectancy, reduction in the lifetime risk of CC, life years saved, quality-adjusted life years (QALYs), net health benefits, lifetime costs, and incremental cost-effectiveness ratios. The willingness-to-pay threshold is defined at 20 000&OV0556;/QALY. Both costs and health outcomes were discounted at an annual rate of 3%. A strategy of 5-year organized HPV testing has similar effectiveness, but higher efficiency than 3 year cytology. Screening alone and vaccination combined with cytology are dominated by vaccination followed by 5-year HPV testing with cytology triage (12 214&OV0556;/QALY). The optimal age for both ending screening and switching age from cytology to HPV testing in older women is 5 years later for unvaccinated than for vaccinated women. Net health benefits decrease faster with diminishing vaccination coverage than screening coverage. Primary HPV DNA testing is more effective and cost-effective than current cytological screening. Vaccination uptake improvements and a gradual change toward an organized screening practice are critical components for achieving higher effectiveness and efficiency in the prevention of CC in Spain. PMID- 26375247 TI - The Effect of Mature Adipocyte-Derived Dedifferentiated Fat (DFAT) Cells on a Dorsal Skin Flap Model. AB - BACKGROUND: Dedifferentiated fat (DFAT) cells, isolated from mature adipose cell, have high proliferative potential and pluripotency. We report on the expansion of flap survival areas on the back of rats administrating DFAT cells. MATERIALS AND METHODS: Intraperitoneal adipose tissue was collected from a male Sprague-Dawley (SD) rat. The mature fat cells were cultured on the ceiling surface of culture flask to isolate DFAT cells. On day 7 of the culture, the flask was inverted to allow normal adherent culture. A dorsal caudal-based random pattern flap measuring 2 * 9 cm was raised on each SD rat. We prepared a control group (n = 10) and a flap base injection group in which DFAT cells were injected 2 cm from the flap base (n = 10) and a flap center DFAT injection group (n = 10). In which DFAT cells at 1 * 106 cells/0.1 ml were injected beneath the skin muscle layers of the flap. The flap survival areas were assessed on day 14 after surgery. RESULTS: The mean flap survival rates of the control group, flap center injection group and flap base injection group were 53.6 +/- 6.1%, 50.6 +/- 6.4% and 65.8 +/ 2.4%, respectively. The flap survival areas significantly expanded in the flap base injection group (p < .05). In H-E staining beneath the skin muscle layer connective tissue thickened in the flap base injection group. In the India ink staining, abundant neovascularization was observed inside the thickened parts. CONCLUSION: The injection of DFAT cells into the flap base promoted the expansion of survival areas. PMID- 26375248 TI - High frequency of additional gene mutations in acute myeloid leukemia with MLL partial tandem duplication: DNMT3A mutation is associated with poor prognosis. AB - The mutational profiles of acute myeloid leukemia (AML) with partial tandem duplication of mixed-lineage leukemia gene (MLL-PTD) have not been comprehensively studied. We studied 19 gene mutations for 98 patients with MLL PTD AML to determine the mutation frequency and clinical correlations. MLL-PTD was screened by reverse-transcriptase PCR and confirmed by real-time quantitative PCR. The mutational analyses were performed with PCR-based assays followed by direct sequencing. Gene mutations of signaling pathways occurred in 63.3% of patients, with FLT3-ITD (44.9%) and FLT3-TKD (13.3%) being the most frequent. 66% of patients had gene mutations involving epigenetic regulation, and DNMT3A (32.7%), IDH2 (18.4%), TET2 (18.4%), and IDH1 (10.2%) mutations were most common. Genes of transcription pathways and tumor suppressors accounted for 23.5% and 10.2% of patients. RUNX1 mutation occurred in 23.5% of patients, while none had NPM1 or double CEBPA mutation. 90.8% of MLL-PTD AML patients had at least one additional gene mutation. Of 55 MLL-PTD AML patients who received standard chemotherapy, age older than 50 years and DNMT3A mutation were associated with inferior outcome. In conclusion, gene mutations involving DNA methylation and activated signaling pathway were common co-existed gene mutations. DNMT3A mutation was a poor prognostic factor in MLL-PTD AML. PMID- 26375249 TI - RD3 loss dictates high-risk aggressive neuroblastoma and poor clinical outcomes. AB - Clinical outcomes for high-risk neuroblastoma patients remains poor, with only 40 50% 5-Year overall survival (OS) and <10% long-term survival. The ongoing acquisition of genetic/molecular rearrangements in undifferentiated neural crest cells may endorse neuroblastoma progression. This study recognized the loss of Retinal Degeneration protein 3, RD3 in aggressive neuroblastoma, and identified its influence in better clinical outcomes and defined its novel metastasis suppressor function. The results showed ubiquitous expression of RD3 in healthy tissues, complete-loss and significant TNM-stage association of RD3 in clinical samples. RD3-loss was intrinsically associated with reduced OS, abridged relapse free survival, aggressive stage etc., in neuroblastoma patient cohorts. RD3 was transcriptionally and translationally regulated in metastatic site-derived aggressive (MSDAC) cells (regardless of CSC status) ex vivo and in tumor manifolds from metastatic sites in reproducible aggressive disease models in vivo. Re-expressing RD3 in MSDACs reverted their metastatic potential both in vitro and in vivo. Conversely muting RD3 in neuroblastoma cells not only heightened invasion/migration but also dictated aggressive disease with metastasis. These results demonstrate the loss of RD3 in high-risk neuroblastoma, its novel, thus-far unrecognized metastasis suppressor function and further imply that RD3-loss may directly relate to tumor aggressiveness and poor clinical outcomes. PMID- 26375250 TI - Epigallocatechin gallate affects glucose metabolism and increases fitness and lifespan in Drosophila melanogaster. AB - In this study, we tested whether a standardized epigallocatechin-3-gallate (EGCG) rich green tea extract (comprising > 90% EGCG) affects fitness and lifespan as well as parameters of glucose metabolism and energy homeostasis in the fruit fly, Drosophila melanogaster. Following the application of the green tea extract a significant increase in the mean lifespan (+ 3.3 days) and the 50% survival (+ 4.3 days) as well as improved fitness was detected. These effects went along an increased expression of Spargel, the homolog of mammalian PGC1alpha, which has been reported to affect lifespan in flies. Intriguingly, in flies, treatment with the green tea extract decreased glucose concentrations, which were accompanied by an inhibition of alpha-amylase and alpha-glucosidase activity. Computational docking analysis proved the potential of EGCG to dock into the substrate binding pocket of alpha-amylase and to a greater extent into alpha-glucosidase. Furthermore, we demonstrate that EGCG downregulates insulin-like peptide 5 and phosphoenolpyruvate carboxykinase, major regulators of glucose metabolism, as well as the Drosophila homolog of leptin, unpaired 2. We propose that a decrease in glucose metabolism in connection with an upregulated expression of Spargel contribute to the better fitness and the extended lifespan in EGCG-treated flies. PMID- 26375253 TI - Wear Compliance and Activity in Children Wearing Wrist- and Hip-Mounted Accelerometers. AB - PURPOSE: This study aimed to 1) explore children's compliance to wearing wrist- and hip-mounted accelerometers, 2) compare children's physical activity (PA) derived from raw accelerations of wrist and hip, and 3) examine differences in raw and counts PA measured by hip-worn accelerometry. METHODS: One hundred and twenty-nine 9- to 10-yr-old children wore a wrist-mounted GENEActiv accelerometer (GAwrist) and a hip-mounted ActiGraph GT3X+ accelerometer (AGhip) for 7 d. Both devices measured raw accelerations, and the AGhip also provided count-based data. RESULTS: More children wore the GAwrist than those from the AGhip regardless of wear time criteria applied (P < 0.001-0.035). Raw data signal vector magnitude (r = 0.68), moderate PA (MPA) (r = 0.81), vigorous PA (VPA) (r = 0.85), and moderate to-vigorous PA (MVPA) (r = 0.83) were strongly associated between devices (P < 0.001). GAwrist signal vector magnitude (P = 0.001), MPA (P = 0.037), VPA (P = 0.002), and MVPA (P = 0.016) were significantly greater than those from the AGhip. According to GAwrist raw data, 86.9% of children engaged in at least 60 min . d(-1) of MVPA, compared with 19% for AGhip. ActiGraph MPA (raw) was 42.00 +/- 1.61 min . d(-1) compared with 35.05 +/- 0.99 min . d(-1) (counts) (P = 0.02). ActiGraph VPA was 7.59 +/- 0.46 min . d(-1) (raw) and 37.06 +/- 1.85 min . d(-1) (counts; P = 0.19). CONCLUSIONS: In children, accelerometer wrist placement promotes superior compliance than the hip. Raw accelerations were significantly higher for GAwrist compared with those for AGhip possibly because of placement location and technical differences between devices. AGhip PA calculated from raw accelerations and counts differed substantially, demonstrating that PA outcomes derived from cut points for raw output and counts cannot be directly compared. PMID- 26375251 TI - Atorvastatin along with imipenem attenuates acute lung injury in sepsis through decrease in inflammatory mediators and bacterial load. AB - Lung is one of the vital organs which is affected during the sequential development of multi-organ dysfunction in sepsis. The purpose of the present study was to examine whether combined treatment with atorvastatin and imipenem could attenuate sepsis-induced lung injury in mice. Sepsis was induced by caecal ligation and puncture. Lung injury was assessed by the presence of lung edema, increased vascular permeability, increased inflammatory cell infiltration and cytokine levels in broncho-alveolar lavage fluid (BALF). Treatment with atorvastatin along with imipenem reduced the lung bacterial load and pro inflammatory cytokines (IL-1beta and TNFalpha) level in BALF. The markers of pulmonary edema such as microvascular leakage and wet-dry weight ratio were also attenuated. This was further confirmed by the reduced activity of MPO and ICAM-1 mRNA expression, indicating the lesser infiltration and adhesion of inflammatory cells to the lungs. Again, expression of mRNA and protein level of iNOS in lungs was also reduced in the combined treatment group. Based on the above findings it can be concluded that, combined treatment with atorvastatin and imipenem dampened the inflammatory response and reduced the bacterial load, thus seems to have promising therapeutic potential in sepsis-induced lung injury in mice. PMID- 26375252 TI - Protein-Protein Interfaces in Viral Capsids Are Structurally Unique. AB - Viral capsids exhibit elaborate and symmetrical architectures of defined sizes and remarkable mechanical properties not seen with cellular macromolecular complexes. Given the uniqueness of the higher-order organization of viral capsid proteins in the virosphere, we explored the question of whether the patterns of protein-protein interactions within viral capsids are distinct from those in generic protein complexes. Our comparative analysis involving a non-redundant set of 551 inter-subunit interfaces in viral capsids from VIPERdb and 20,014 protein protein interfaces in non-capsid protein complexes from the Protein Data Bank found 418 generic protein-protein interfaces that share similar physicochemical patterns with some protein-protein interfaces in the capsid set, using the program PCalign we developed for comparing protein-protein interfaces. This overlap in the structural space of protein-protein interfaces is significantly small, with a p-value <0.0001, based on a permutation test on the total set of protein-protein interfaces. Furthermore, the generic protein-protein interfaces that bear similarity in their spatial and chemical arrangement with capsid ones are mostly small in size with fewer than 20 interfacial residues, which results from the relatively limited choices of natural design for small interfaces rather than having significant biological implications in terms of functional relationships. We conclude based on this study that protein-protein interfaces in viral capsids are non-representative of patterns in the smaller, more compact cellular protein complexes. Our finding highlights the design principle of building large biological containers from repeated, self-assembling units and provides insights into specific targets for antiviral drug design for improved efficacy. PMID- 26375254 TI - A Microbiopsy Method for Immunohistological and Morphological Analysis: A Pilot Study. AB - INTRODUCTION: The fine aspiration microbiopsy is a relatively new biopsy technique, which allows muscle physiologists to sample skeletal muscle less invasively. However, the small sample size obtained is often deemed insufficient for certain analyses. The aim of the current study was to develop procedures for muscle fiber morphology and immunohistological analysis from a microbiopsy technique. METHODS: Microbiopsies of the vastus lateralis were taken with a 14 gauge microbiopsy needle from four healthy men on two separate occasions. The tissue was oriented in a cryomold, embedded in Tissue-Tek(r) then frozen in liquid nitrogen cooled isopentane. The muscle sections were stained with hematoxylin and eosin, laminin, MHCI, MHCIIa, and Pax7 for fiber number, mean fiber area, muscle fiber typing, and satellite cell observation. RESULTS: The mean +/- SD (range) microbiopsy sample weight was 18.3 +/- 2.9 mg (14-22 mg). The mean fiber number within the microbiopsy specimens was 150.4 +/- 120.6 (64-366). All viable fibers were measured in each sample, and the mean fiber area was 4385.1 +/- 1265.8 MUm2 (977.0-10,132.93 MUm2). There was no significant time difference (P = 0.69) in mean fiber area. DISCUSSION: Results suggest the potential use of a "minimally invasive" muscle biopsy technique for immunohistological and morphological analysis. This could provide clinicians and investigators additional data in future research. Further investigations are needed to determine the usefulness and potential limiting factors of this technique. PMID- 26375255 TI - Hospitalization for Total Knee Replacement Among Inpatients Aged 45 and Over: United States, 2000-2010. AB - In 2010, total knee replacement was the most frequently performed inpatient procedure on adults aged 45 and over. In the 11-year period from 2000 through 2010, an estimated 5.2 million total knee replacements were performed. Adults aged 45 and over comprised 98.1% of those surgeries. This report uses data from the National Hospital Discharge Survey (NHDS) to present trends in the rate of hospitalizations for total knee replacement, mean age at hospitalization, and discharge status for inpatients aged 45 and over from 2000 through 2010. PMID- 26375256 TI - Strongly Dichroic Organic Films via Controlled Assembly of Modular Aromatic Charge-Transfer Liquid Crystals. AB - The formation of highly anisotropic organic thin films based on the designed self assembly of mixed-stack liquid crystals is reported. A series of alkoxyanthracene donors is combined in a modular fashion with a naphthalenediimide acceptor to generate new charge-transfer columnar liquid crystals. Materials characterization and molecular modeling provides insight into structure-function relationships in these organic materials that lead to the striking bulk dichroic properties of certain molecular assemblies. PMID- 26375260 TI - Dispositional sources of sanction perceptions: Emotionality, cognitive style, intolerance of ambiguity, and self-efficacy. AB - This study contributes to efforts to identify the sources of arrest risk perceptions and ambiguity (or lack of confidence) in such perceptions. Drawing on dual-process theories of reasoning, we argue that arrest risk perceptions often represent intuitive judgments that are influenced by cognitive heuristics and dispositional attributes. Multivariate regression models are estimated with data from 3 national surveys to test 6 hypotheses about the relationships between specific dispositional attributes and perceived arrest risk and ambiguity. We find evidence that dispositional positive affect and intolerance of ambiguity are both positively related to perceived arrest risk, and are also both negatively related to ambiguity. We also find evidence that cognitive reflection and general self-efficacy are, respectively, positively and negatively associated with ambiguity. Mixed evidence emerges about whether cognitive reflection is related to risk perceptions, and about whether either dispositional negative affect or thoughtfully reflective decision making correlate with ambiguity. Taken together, the results provide partial support for each of our hypotheses, and suggest that dispositional attributes are important sources of perceptions of arrest risk as well as of ambiguity in such perceptions. PMID- 26375259 TI - Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling. AB - Intracellular lipopolysaccharide from Gram-negative bacteria including Escherichia coli, Salmonella typhimurium, Shigella flexneri, and Burkholderia thailandensis activates mouse caspase-11, causing pyroptotic cell death, interleukin-1beta processing, and lethal septic shock. How caspase-11 executes these downstream signalling events is largely unknown. Here we show that gasdermin D is essential for caspase-11-dependent pyroptosis and interleukin 1beta maturation. A forward genetic screen with ethyl-N-nitrosourea-mutagenized mice links Gsdmd to the intracellular lipopolysaccharide response. Macrophages from Gsdmd(-/-) mice generated by gene targeting also exhibit defective pyroptosis and interleukin-1beta secretion induced by cytoplasmic lipopolysaccharide or Gram-negative bacteria. In addition, Gsdmd(-/-) mice are protected from a lethal dose of lipopolysaccharide. Mechanistically, caspase-11 cleaves gasdermin D, and the resulting amino-terminal fragment promotes both pyroptosis and NLRP3-dependent activation of caspase-1 in a cell-intrinsic manner. Our data identify gasdermin D as a critical target of caspase-11 and a key mediator of the host response against Gram-negative bacteria. PMID- 26375261 TI - An Advanced Semimetal-Organic Bi Spheres-g-C3N4 Nanohybrid with SPR-Enhanced Visible-Light Photocatalytic Performance for NO Purification. AB - To achieve efficient photocatalytic air purification, we constructed an advanced semimetal-organic Bi spheres-g-C3N4 nanohybrid through the in-situ growth of Bi nanospheres on g-C3N4 nanosheets. This Bi-g-C3N4 compound exhibited an exceptionally high and stable visible-light photocatalytic performance for NO removal due to the surface plasmon resonance (SPR) endowed by Bi metal. The SPR property of Bi could conspicuously enhance the visible-light harvesting and the charge separation. The electromagnetic field distribution of Bi spheres involving SPR effect was simulated and reaches its maximum in close proximity to the Bi particle surface. When the Bi metal content was controlled at 25%, the corresponding Bi-g-C3N4 displayed outstanding photocatalytic capability and transcended those of other visible-light photocatalysts. The Bi-g-C3N4 exhibited a high structural stability under repeated photocatalytic runs. A new visible light-induced SPR-based photocatalysis mechanism with Bi-g-C3N4 was proposed on the basis of the DMPO-ESR spin-trapping. The photoinduced electrons could transfer from g-C3N4 to the Bi metal, as revealed with time-resolved fluorescence spectra. The function of Bi semimetal as a plasmonic cocatalyst for boosting visible light photocatalysis was similar to that of noble metals, which demonstrated a great potential of utilizing the economically feasible Bi element as a substitute for noble metals for the advancement of photocatalysis efficiency. PMID- 26375263 TI - Setting mastery learning standards. AB - Mastery learning is an instructional approach in which educational progress is based on demonstrated performance, not curricular time. Learners practice and retest repeatedly until they reach a designated mastery level; the final level of achievement is the same for all, although time to mastery may vary. Given the unique properties of mastery learning assessments, a thoughtful approach to establishing the performance levels and metrics that determine when a learner has demonstrated mastery is essential.Standard-setting procedures require modification when used for mastery learning settings in health care, particularly regarding the use of evidence-based performance data, the determination of appropriate benchmark or comparison groups, and consideration of patient safety consequences. Information about learner outcomes and past performance data of learners successful at the subsequent level of training can be more helpful than traditional information about test performance of past examinees. The marginally competent "borderline student" or "borderline group" referenced in traditional item-based and examinee-based procedures will generally need to be redefined in mastery settings. Patient safety considerations support conjunctive standards for key knowledge and skill subdomains and for items that have an impact on clinical outcomes. Finally, traditional psychometric indices used to evaluate the quality of standards do not necessarily reflect critical measurement properties of mastery assessments. Mastery learning and testing are essential to the achievement and assessment of entrustable professional activities and residency milestones. With careful attention, sound mastery standard-setting procedures can provide an essential step toward improving the effectiveness of health professions education, patient safety, and patient care. PMID- 26375264 TI - The charismatic journey of mastery learning. AB - A collection of articles in this issue examine the concept of mastery learning, underscoring that our journey is from a 19th-century construct for assuring skill development (i.e., completing a schedule of rotations driven by the calendar) to a 21st-century sequence of learning opportunities focused on acquiring mastery of special key competencies within clerkships or other activities. Mastery learning processes and standards have the potential to clarify learning goals and competency measurement issues in medical education. Although mastery learning methods originally focused on developing learners' competency with skillful procedures, the author of this Commentary posits that mastery learning methods may be usefully applied more extensively to broader domains of skillful practice, especially those practices that can be linked to outcomes of care. The transition to mastery-focused criteria for educational advancement is laudatory, but challenges will be encountered in the journey to mastery education. The author examines several of these potential challenges, including expansion of mastery learning approaches to effective but relational clinician advice-giving and counseling behaviors, developing criteria for choosing critical competencies that can be linked to outcomes, avoiding a excessively fragmented approach to mastery measurement, and dealing with "educational comorbidity." PMID- 26375265 TI - Does Making the Numerical Values of Verbal Anchors on a Rating Scale Available to Examiners Inflate Scores on a Long Case Examination? AB - PURPOSE: Rating scales are frequently used for scoring assessments in medical education. The effect of changing the structural elements of a rating scale on students' examination scores has received little attention in the medical education literature. This study assessed the impact of making the numerical values of verbal anchors on a rating scale available to examiners in a long case examination (LCE). METHOD: During the 2011-2012 academic year, the numerical values of verbal anchors on a rating scale for an internal medicine clerkship LCE were made available to faculty examiners. Historically, and specifically in the control year of 2010-2011, examiners only saw the scale's verbal anchors and were blinded to the associated numerical values. To assess the impact of this change, the authors compared students' LCE scores between the two cohort years. To assess for differences between the two cohorts, they compared students' scores on other clerkship assessments, which remained the same between the two cohorts. RESULTS: From 2010-2011 (n = 226) to 2011-2012 (n = 218), the median LCE score increased significantly from 82.11% to 85.02% (P < .01). Students' performance on the other clerkship assessments was similar between cohorts. CONCLUSIONS: Providing examiners with the numerical values of verbal anchors on a rating scale, in addition to the verbal anchors themselves, led to a significant increase in students' scores on an internal medicine clerkship LCE. When constructing or changing rating scales, educators must consider the potential impact of the rating scale structure on students' scores. PMID- 26375266 TI - A market approach to better care at lower cost. AB - The Affordable Care Act expanded health insurance coverage in the United States but did little to address the structural problems that plague the U.S. health care system. Controlling cost while maintaining or improving access to quality care requires a more fundamental reform based on market principles. Such an approach means aligning the financial incentives of patients and providers to promote smarter spending. It also requires better information and more flexible regulation to promote well-functioning competitive markets. Key elements of these reforms include setting reasonable limits on subsidies for Medicare, Medicaid, and private health insurance; modernizing the Medicare program and adopting reforms that promote competition between traditional Medicare and Medicare Advantage; allowing greater flexibility for states in running their Medicaid programs; enacting smarter regulations to protect consumers without imposing greater inefficiency on the health market; and promoting more direct consumer involvement in all phases of their health and health care. These changes will challenge academic medical centers as a new era of creativity and competition emerges in the health care market. PMID- 26375267 TI - Acquisition and maintenance of medical expertise: a perspective from the expert performance approach with deliberate practice. AB - As a part of a special collection in this issue of Academic Medicine, which is focused on mastery learning in medical education, this Perspective describes how the expert-performance approach with deliberate practice is consistent with many characteristics of mastery learning. Importantly, this Perspective also explains how the expert-performance approach provides a very different perspective on the acquisition of skill. Whereas traditional education with mastery learning focuses on having students attain an adequate level of performance that is based on goals set by the existing curricula, the expert-performance approach takes an empirical approach and first identifies the final goal of training-namely, reproducibly superior objective performance (superior patient outcomes) for individuals in particular medical specialties. Analyzing this superior complex performance reveals three types of mental representations that permit expert performers to plan, execute, and monitor their own performance. By reviewing research on medical performance and education, the author describes evidence for these representations and their development within the expert-performance framework. He uses the research to generate suggestions for improved training of medical students and professionals. Two strategies-designing learning environments with libraries of cases and creating opportunities for individualized teacher-guided training-should enable motivated individuals to acquire a full set of refined mental representations. Providing the right resources to support the expert performance approach will allow such individuals to become self-regulated learners-that is, members of the medical community who have the tools to improve their own and their team members' performances throughout their entire professional careers. PMID- 26375268 TI - Training and Assessing Interprofessional Virtual Teams Using a Web-Based Case System. AB - PURPOSE: Today, clinical care is often provided by interprofessional virtual teams-groups of practitioners who work asynchronously and use technology to communicate. Members of such teams must be competent in interprofessional practice and the use of information technology, two targets for health professions education reform. The authors created a Web-based case system to teach and assess these competencies in health professions students. METHOD: They created a four-module, six-week geriatric learning experience using a Web-based case system. Health professions students were divided into interprofessional virtual teams. Team members received profession-specific information, entered a summary of this information into the case system's electronic health record, answered knowledge questions about the case individually, then collaborated asynchronously to answer the same questions as a team. Individual and team knowledge scores and case activity measures--number of logins, message board posts/replies, views of message board posts--were tracked. RESULTS: During academic year 2012-2013, 80 teams composed of 522 students from medicine, nursing, pharmacy, and social work participated. Knowledge scores varied by profession and within professions. Team scores were higher than individual scores (P < .001). Students and teams with higher knowledge scores had higher case activity measures. Team score was most highly correlated with number of message board posts/replies and was not correlated with number of views of message board posts. CONCLUSIONS: This Web-based case system provided a novel approach to teach and assess the competencies needed for virtual teams. This approach may be a valuable new tool for measuring competency in interprofessional practice. PMID- 26375269 TI - Mastery learning: it is time for medical education to join the 21st century. AB - Clinical medical education in the 21st century is grounded in a 19th-century model that relies on longitudinal exposure to patients as the curriculum focus. The assumption is that medical students and postgraduate residents will learn from experience, that vicarious or direct involvement in patient care is the best teacher. The weight of evidence shows, however, that results from such traditional clinical education are uneven at best. Educational inertia endorsed until recently by medical school accreditation policies has maintained the clinical medical education status quo for decades.Mastery learning is a new paradigm for medical education. Basic principles of mastery learning are that educational excellence is expected and can be achieved by all learners and that little or no variation in measured outcomes will result. This Commentary describes the origins of mastery learning and presents its essential features. The Commentary then introduces the eight reports that comprise the mastery learning cluster for this issue of Academic Medicine. The reports are intended to help medical educators recognize advantages of the mastery model and begin to implement mastery learning at their own institutions. The Commentary concludes with brief statements about future directions for mastery learning program development and research in medical education. PMID- 26375270 TI - Recommendations for Reporting Mastery Education Research in Medicine (ReMERM). AB - Guidelines for reporting several types of medical studies have been described in the literature. However, there are no current guidelines to report studies on mastery learning curriculum development and trainee evaluation in medical education. Such guidelines will be important because medical education is moving toward a competency-based model. The authors sought to define standards for the evaluation of mastery learning curricula using previously published guidelines in related fields and expert review.The authors reviewed previously published guidelines from clinical medicine, medical education, and the social sciences. Six authors with expertise in mastery learning curricula, performance assessment, and medical education compiled and reached agreement about a list of guidelines. The authors later circulated the list to 12 other experts and made revisions. A final list of guidelines was established and received group consensus. The Reporting Mastery Education Research in Medicine (ReMERM) guidelines have 22 categories with 38 items considered to be imperative for reporting a mastery learning research study. Details about each item, with a specific focus on those unique to mastery learning, are discussed.The ReMERM guidelines highlight the importance of developing rigorous curricula that embody reliable measures which yield valid decisions about achievement among medical learners. These guidelines should improve the quality of reporting and help educators, authors, peer reviewers, journal editors, and readers to better understand and evaluate mastery learning research. With this shift to competency-based medical education, the ReMERM guidelines should help meet medical educators' needs to achieve these new goals. PMID- 26375271 TI - Beyond the simulation laboratory: a realist synthesis review of clinical outcomes of simulation-based mastery learning. AB - PURPOSE: Translational educational outcomes have been defined as starting in simulation laboratories (T1) and moving downstream to improved patient care practices (T2), patient outcomes (T3), and cost/other value outcomes (T4). The authors conducted a realist synthesis review of the literature to evaluate the translational effect of simulation-based mastery learning (SBML) principles beyond the laboratory. They also sought to address future directions in SBML to improve patient care processes and outcomes and, thus, the quality of health care delivery. METHOD: The authors searched multiple databases for simulation-based medical education (SBME) studies published through April 2013. They screened articles using the PICO method-population (P), intervention (I), control (C), outcome (O)-to answer the research question: For (P) any health care providers, does the (I) implementation of SBML training, compared with (C) other training methodologies or no extra training, result in (O) a change in patient care practices or T2-T4 outcomes? Studies implementing SBME interventions with training methodologies that met all SBML principles and reporting T2-T4 outcomes were identified. RESULTS: The 14 included studies used pre/post or cohort study designs; the majority were limited to individual performance and procedural competency. They reported improvement after SBML training in procedure performance, task success, patient discomfort, procedure time, complication rates, or T4 impacts (e.g., cost reduction). CONCLUSIONS: Findings suggest health professions education conducted using SBML methodology can improve patient care processes and outcomes. Further research is needed to understand the translational impact of SBML for nontechnical skills, including teamwork, and skill retention. PMID- 26375272 TI - Structuring feedback and debriefing to achieve mastery learning goals. AB - Mastery learning is a powerful educational strategy in which learners gain knowledge and skills that are rigorously measured against predetermined mastery standards with different learners needing variable time to reach uniform outcomes. Central to mastery learning are repetitive deliberate practice and robust feedback that promote performance improvement. Traditional health care simulation involves a simulation exercise followed by a facilitated postevent debriefing in which learners discuss what went well and what they should do differently next time, usually without additional opportunities to apply the specific new knowledge. Mastery learning approaches enable learners to "try again" until they master the skill in question. Despite the growing body of health care simulation literature documenting the efficacy of mastery learning models, to date insufficient details have been reported on how to design and implement the feedback and debriefing components of deliberate-practice-based educational interventions. Using simulation-based training for adult and pediatric advanced life support as case studies, this article focuses on how to prepare learners for feedback and debriefing by establishing a supportive yet challenging learning environment; how to implement educational interventions that maximize opportunities for deliberate practice with feedback and reflection during debriefing; describing the role of within-event debriefing or "microdebriefing" (i.e., during a pause in the simulation scenario or during ongoing case management without interruption), as a strategy to promote performance improvement; and highlighting directions for future research in feedback and debriefing for mastery learning. PMID- 26375274 TI - Cold-shock based method to induce the discharge of extrusomes in ciliated protists and its efficiency. AB - Extrusomes are ejectable organelles in protists, which are able to discharge their contents to the outside of the cell in response to external stimuli. It is known that a large number of extrusomes functions as organelles for offense or defense in predator-prey interactions among protists and/or microinvertebrates. To date, the main approach to study these interactions was to compare artificially-induced extrusome-deficient cells with normal cells as prey for predators. Commonly applied methods to obtain extrusome-deficient cells use external chemicals, which could alter the viability of cells and/or interfere with the subsequent analysis of the substances (secondary metabolites) contained in the extrusomes. The cold-shock based method here presented has proven to be effective to remove different kinds of extrusomes from several protist species without harming the treated cells and without adding external reagents. This method could be also useful to simplify the related analysis of the chemical nature of the secreted secondary metabolites. PMID- 26375275 TI - Bioinspired Composite Coating with Extreme Underwater Superoleophobicity and Good Stability for Wax Prevention in the Petroleum Industry. AB - Wax deposition is a detrimental problem that happens during crude oil production and transportation, which greatly reduces transport efficiency and causes huge economic losses. To avoid wax deposition, a bioinspired composite coating with excellent wax prevention and anticorrosion properties is developed in this study. The prepared coating is composed of three films, including an electrodeposited Zn film for improving corrosion resistance, a phosphating film for constructing fish scale morphology, and a silicon dioxide film modified by a simple spin-coating method for endowing the surface with superhydrophilicity. Good wax prevention performance has been investigated in a wax deposition test. The surface morphology, composition, wetting behaviors, and stability are systematically studied, and a wax prevention mechanism is proposed, which can be calculated from water film theory. This composite coating strategy which shows excellent properties in both wax prevention and stability is expected to be widely applied in the petroleum industry. PMID- 26375276 TI - Antenatal Determinants of Long-Term Kidney Outcome in Boys with Posterior Urethral Valves. AB - BACKGROUND: Posterior urethral valves (PUV) are the most important cause of end stage renal disease (ESRD) in young boys. The objective of this report was to define the antenatal determinants of long-term postnatal renal outcome in this condition. DESIGN: This was a retrospective cohort analysis. The primary outcome was the development of ESRD defined as starting dialysis or receiving a preemptive kidney transplant. RESULTS: Eighty-two cases of PUV were identified, with 17 (21%) developing ESRD at 6.1 +/- 7.1 years. Cases developing ESRD were more likely diagnosed antenatally (41 vs. 19%, p = 0.05), had a younger gestational age (35.5 +/- 3.4 weeks vs. 37.3 +/- 2.1 weeks, p = 0.02), and on antenatal ultrasound scan were more likely to have oligohydramnios (60 vs. 26%, p = 0.02), renal cortical cysts (47 vs. 17%, p = 0.02), and the combination of oligohydramnios, renal cortical cysts, and increased renal echogenicity (47 vs. 9%, p = 0.002). CONCLUSIONS: In boys with PUV, decreased gestational age, oligohydramnios, renal cysts, and the combination of oligohydramnios, cortical cysts, and echogenic kidneys were associated with ESRD, while the combination was an independent predictor of poor long-term postnatal kidney function. PMID- 26375277 TI - Comparison of the PTSD Checklist (PCL) Administered via a Mobile Device Relative to a Paper Form. AB - Mobile devices are increasingly used to administer self-report measures of mental health symptoms. There are significant differences, however, in the way that information is presented on mobile devices compared to the traditional paper forms that were used to administer such measures. Such differences may systematically alter responses. The present study evaluated if and how responses differed for a self-report measure, the PTSD Checklist (PCL), administered via mobile device relative to paper and pencil. Participants were 153 trauma-exposed individuals who completed counterbalanced administrations of the PCL on a mobile device and on paper. PCL total scores (d = 0.07) and item responses did not meaningfully or significantly differ across administrations. Power was sufficient to detect a difference in total score between administrations determined by prior work of 3.46 with a d = 0.23. The magnitude of differences between administration formats was unrelated to prior use of mobile devices or participant age. These findings suggest that responses to self-report measures administered via mobile device are equivalent to those obtained via paper and they can be used with experienced as well as naive users of mobile devices. PMID- 26375278 TI - Poly(PEGA)-b-poly(L-lysine)-b-poly(L-histidine) Hybrid Vesicles for Tumoral pH Triggered Intracellular Delivery of Doxorubicin Hydrochloride. AB - A series of poly(ethylene glycol) methyl ether acrylate-block-poly(L-lysine) block-poly(L-histidine) [p(PEGA)30-b-p(Lys)25-b-p(His)n] (n = 25, 50, 75, 100) triblock copolypeptides were designed and synthesized for tumoral pH-responsive intracellular release of anticancer drug doxorubicin hydrochloride (Dox). The tumoral acidic pH-responsive hybrid vesicles fabricated were stable at physiological pH 7.4 and could gradually destabilize in acidic pH as a result of pH-induced swelling of the p(His) block. The blank vesicles were nontoxic over a wide concentration range (0.01-100 MUg/mL) in normal cell lines. The tumor acidic pH responsiveness of these vesicles was exploited for intracellular delivery of Dox. Vesicles efficiently encapsulated Dox, and pH-induced destabilization resulted in the controlled and sustained release of Dox in CT26 murine cancer cells, and dose-dependent cytotoxicity. The tumor-specific controlled release Dox from vesicles demonstrates this system represents a promising theranostic agent for tumor-targeted delivery. PMID- 26375279 TI - Correction: Arthritis Induces Early Bone High Turnover, Structural Degradation and Mechanical Weakness. PMID- 26375280 TI - The Accuracy of Diagnosis of an Online Consultation Service Compared With Physical Consultation With a Dermatologist. PMID- 26375282 TI - Routine Eye Screening by an Ophthalmologist Is Clinically Useful for HIV-1 Infected Patients with CD4 Count Less than 200 /MUL. AB - OBJECTIVE: To investigate whether routine eye screening by an ophthalmologist in patients with HIV-1 infection is clinically useful. METHODS: A single-center, retrospective study in Tokyo, Japan. HIV-1-infected patients aged over 17 years who visited our clinic for the first time between January 2004 and December 2013 and underwent full ophthalmologic examination were enrolled. At our clinic, ophthalmologic examination, including dilated retinal examination by indirect ophthalmoscopy was routinely conducted by ophthalmologists on the first visit. The prevalence of ophthalmologic diseases and associated factors including the existence of ocular symptoms were analyzed. RESULTS: Of the 1,515 study patients, cytomegalovirus retinitis (CMV-R) was diagnosed in 24 (2%) patients, HIV retinopathy (HIV-R) in 127 (8%), cataract in 31 (2%), ocular syphilis in 4 (0.3%), and uveitis with unknown cause in 8 (0.5%). Other ocular diseases were diagnosed in 14 patients. The CD4 count was <200 /MUL in all CMV-R cases and 87% of HIV-R. The prevalence of any ocular diseases, CMV-R, and HIV-R in patients with CD4 <200 /MUL were 22%, 3%, and 15%, respectively, whereas for those with CD4 >=200 /MUL were 5%, 0%, and 2%, respectively. No ocular symptoms were reported by 71% of CMV-R cases and 82% of patients with any ocular diseases. CONCLUSIONS: Routine ophthalmologic screening is recommended for HIV-1-infected patients with CD4 <200 /MUL in resource-rich settings based on the high prevalence of ocular diseases within this CD4 count category and because most patients with ocular diseases, including those with CMV-R, were free of ocular symptoms. PMID- 26375281 TI - Co-Administration of Cholesterol-Lowering Probiotics and Anthraquinone from Cassia obtusifolia L. Ameliorate Non-Alcoholic Fatty Liver. AB - Non-alcoholic fatty liver disease (NAFLD) has become a common liver disease in recent decades. No effective treatment is currently available. Probiotics and natural functional food may be promising therapeutic approaches to this disease. The present study aims to investigate the efficiency of the anthraquinone from Cassia obtusifolia L. (AC) together with cholesterol-lowering probiotics (P) to improve high-fat diet (HFD)-induced NAFLD in rat models and elucidate the underlying mechanism. Cholesterol-lowering probiotics were screened out by MRS cholesterol broth with ammonium ferric sulfate method. Male Sprague-Dawley rats were fed with HFD and subsequently administered with AC and/or P. Lipid metabolism parameters and fat synthesis related genes in rat liver, as well as the diversity of gut microbiota were evaluated. The results demonstrated that, compared with the NAFLD rat, the serum lipid levels of treated rats were reduced effectively. Besides, cholesterol 7alpha-hydroxylase (CYP7A1), low density lipoprotein receptor (LDL-R) and farnesoid X receptor (FXR) were up-regulated while the expression of 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMGCR) was reduced. The expression of peroxisome proliferator activated receptor (PPAR) alpha protein was significantly increased while the expression of PPAR-gamma and sterol regulatory element binding protein-1c (SREBP-1c) was down-regulated. In addition, compared with HFD group, in AC, P and AC+P group, the expression of intestinal tight-junction protein occludin and zonula occluden-1 (ZO-1) were up regulated. Furthermore, altered gut microbiota diversity after the treatment of probiotics and AC were analysed. The combination of cholesterol-lowering probiotics and AC possesses a therapeutic effect on NAFLD in rats by up regulating CYP7A1, LDL-R, FXR mRNA and PPAR-alpha protein produced in the process of fat metabolism while down-regulating the expression of HMGCR, PPAR-gamma and SREBP-1c, and through normalizing the intestinal dysbiosis and improving the intestinal mucosal barrier function. PMID- 26375283 TI - Detection of Gene Flow from Sexual to Asexual Lineages in Thrips tabaci (Thysanoptera: Thripidae). AB - Populations of Thrips tabaci are known to have two sympatric but genetically isolated reproductive modes, arrhenotoky (sexual reproduction) and thelytoky (asexual reproduction). Herein, we report behavioral, ecological and genetic studies to determine whether there is gene flow between arrhenotokous and thelytokous T. tabaci. We did not detect significant preference by arrhenotokous males to mate with females of a particular reproductive mode, nor did we detect significant behavioral differences between arrhenotokous males mated with arrhenotokous or thelytokous females in their pre-copulation, copulation duration and mating frequency. Productive gene transfer resulting from the mating between the two modes was experimentally confirmed. Gene transfer from arrhenotokous T. tabaci to thelytokous T. tabaci was further validated by confirmation of the passage of the arrhenotokous male-originated nuclear gene (histone H3 gene) allele to the F2 generation. These behavioral, ecological and genetic studies confirmed gene transfer from the sexual arrhenotokous mode to the asexual thelytokous mode of T. tabaci in the laboratory. These results demonstrate that asexual T. tabaci populations may acquire genetic variability from sexual populations, which could offset the long-term disadvantage of asexual reproduction. PMID- 26375284 TI - Relationship between Body Mass Composition, Bone Mineral Density, Skin Fibrosis and 25(OH) Vitamin D Serum Levels in Systemic Sclerosis. AB - A reduced bone mineral density (BMD) is observed in several rheumatic autoimmune diseases, including Systemic Sclerosis (SSc); nevertheless, data concerning the possible determinants of bone loss in this disease are not fully investigated. The aim of this study is to evaluate the relationship between BMD, body mass composition, skin sclerosis and serum Vitamin D levels in two subsets of SSc patients. 64 post-menopausal SSc patients, classified as limited cutaneous (lcSSc) or diffuse cutaneous (dcSSc) SSc, were studied. As control, 35 healthy post-menopausal women were recruited. Clinical parameters were evaluated, including the extent of skin involvement. BMD at lumbar spine, hip, femoral neck and body mass composition were determined by dual-energy X-ray absorptiometry. Serum calcium, phosphorus, alkaline phosphatase, urine pyridinium cross-links, intact parathyroid hormone and 25-hydroxyvitamin D (25OHD) were measured. BMD at spine, femoral neck and total hip was significantly lower in SSc patients compared to controls. In dcSSc subset, BMD at spine, femoral neck and total hip was significantly lower compared to lcSSc. No differences in both fat and lean mass were found in the three study groups even if patients with dcSSc showed a slightly lower total body mass compared to healthy controls. Total mineral content was significantly reduced in dSSc compared to both healthy subjects and lcSSc group. Hypovitaminosis D was observed both in healthy post-menopausal women and in SSc patients, but 25OHD levels were significantly lower in dcSSc compared to lcSSc and inversely correlated with the extent of skin thickness. These results support the hypothesis that the extent of skin involvement in SSc patients could be an important factor in determining low circulating levels of 25OHD, which in turn could play a significant role in the reduction of BMD and total mineral content. PMID- 26375285 TI - The Green Tea Component (-)-Epigallocatechin-3-Gallate Sensitizes Primary Endothelial Cells to Arsenite-Induced Apoptosis by Decreasing c-Jun N-Terminal Kinase-Mediated Catalase Activity. AB - The green tea component (-)-epigallocatechin-3-gallate (EGCG) has been shown to sensitize many different types of cancer cells to anticancer drug-induced apoptosis, although it protects against non-cancerous primary cells against toxicity from certain conditions such as exposure to arsenic (As) or ultraviolet irradiation. Here, we found that EGCG promotes As-induced toxicity of primary cultured bovine aortic endothelial cells (BAEC) at doses in which treatment with each chemical alone had no such effect. Increased cell toxicity was accompanied by an increased condensed chromatin pattern and fragmented nuclei, cleaved poly(ADP-ribose) polymerase (PARP), activity of the pro-apoptotic enzymes caspases 3, 8 and 9, and Bax translocation into mitochondria, suggesting the involvement of an apoptotic signaling pathway. Fluorescence activated cell sorting analysis revealed that compared with EGCG or As alone, combined EGCG and As (EGCG/As) treatment significantly induced production of reactive oxygen species (ROS), which was accompanied by decreased catalase activity and increased lipid peroxidation. Pretreatment with N-acetyl-L-cysteine or catalase reversed EGCG/As-induced caspase activation and EC toxicity. EGCG/As also increased the phosphorylation of c-Jun N-terminal kinase (JNK), which was not reversed by catalase. However, pretreatment with the JNK inhibitor SP600125 reversed all of the observed effects of EGCG/As, suggesting that JNK may be the most upstream protein examined in this study. Finally, we also found that all the observed effects by EGCG/As are true for other types of EC tested. In conclusion, this is firstly to show that EGCG sensitizes non-cancerous EC to As-induced toxicity through ROS-mediated apoptosis, which was attributed at least in part to a JNK activated decrease in catalase activity. PMID- 26375286 TI - Energy Drinks, Alcohol, Sports and Traumatic Brain Injuries among Adolescents. AB - IMPORTANCE: The high prevalence of traumatic brain injuries (TBI) among adolescents has brought much focus to this area in recent years. Sports injuries have been identified as a main mechanism. Although energy drinks, including those mixed with alcohol, are often used by young athletes and other adolescents they have not been examined in relation to TBI. OBJECTIVE: We report on the prevalence of adolescent TBI and its associations with energy drinks, alcohol and energy drink mixed in with alcohol consumption. DESIGN, SETTINGS AND PARTICIPANTS: Data were derived from the Centre for Addiction and Mental Health's 2013 Ontario Student Drug Use and Health Survey (OSDUHS). This population-based cross sectional school survey included 10,272 7th to 12th graders (ages 11-20) who completed anonymous self-administered questionnaires in classrooms. MAIN OUTCOME MEASURES: Mild to severe TBI were defined as those resulting in a loss of consciousness for at least five minutes, or being hospitalized for at least one night. Mechanism of TBI, prevalence estimates of TBI, and odds of energy drink consumption, alcohol use, and consumption of energy drinks mixed with alcohol are assessed. RESULTS: Among all students, 22.4% (95% CI: 20.7, 24.1) reported a history of TBI. Sports injuries remain the main mechanism of a recent (past year) TBI (45.5%, 95% CI: 41.0, 50.1). Multinomial logistic regression showed that relative to adolescents who never sustained a TBI, the odds of sustaining a recent TBI were greater for those consuming alcohol, energy drinks, and energy drinks mixed in with alcohol than abstainers. Odds ratios were higher for these behaviors among students who sustained a recent TBI than those who sustained a former TBI (lifetime but not past 12 months). Relative to recent TBI due to other causes of injury, adolescents who sustained a recent TBI while playing sports had higher odds of recent energy drinks consumption than abstainers. CONCLUSIONS AND RELEVANCE: TBI remains a disabling and common condition among adolescents and the consumption of alcohol, energy drinks, and alcohol mixed with energy drinks further increase the odds of TBI among adolescents. These associations warrant further investigation. PMID- 26375287 TI - Tobacco Stained Fingers and Its Association with Death and Hospital Admission: A Retrospective Cohort Study. AB - BACKGROUND: Among smokers, the presence of tobacco stains on fingers has recently been associated with a high prevalence of tobacco related conditions and alcohol abuse. OBJECTIVE: we aimed to explore tobacco stains as a marker of death and hospital readmission. METHOD: Seventy-three smokers presenting tobacco-tar staining on their fingers and 70 control smokers were followed during a median of 5.5 years in a retrospective cohort study. We used the Kaplan-Meier survival analysis and the log-rank test to compare mortality and hospital readmission rates among smokers with and smokers without tobacco stains. Multivariable Cox models were used to adjust for confounding factors: age, gender, pack-year unit smoked, cancer, harmful alcohol use and diabetes. The number of hospital admissions was compared through a negative binomial regression and adjusted for the follow-up time, diabetes, and alcohol use. RESULTS: Forty-three patients with tobacco-stained fingers died compared to 26 control smokers (HR 1.6; 95%CI: 1.0 to 2.7; p 0.048). The association was not statistically significant after adjustment. Patients with tobacco-stained fingers needed a readmission earlier than smokers without stains (HR 2.1; 95%CI: 1.4 to 3.1; p<0.001), and more often (incidence rate ratio (IRR) 1.6; 95%CI: 1.1 to 2.1). Associations between stains and the first hospital readmission (HR 1.6; 95%CI: 1.0 to 2.5), and number of readmissions (IRR 1.5; 95%CI: 1.1 to 2.1) persisted after adjustment for confounding factors. CONCLUSIONS: Compared to other smokers, those presenting tobacco-stained fingers have a high unadjusted mortality rate and need early and frequent hospital readmission even when controlling for confounders. PMID- 26375289 TI - The Undiagnosed Diseases Network of the National Institutes of Health: A National Extension. PMID- 26375290 TI - Are Mortality and Acute Morbidity in Patients Presenting With Nonspecific Complaints Predictable Using Routine Variables? AB - OBJECTIVES: Patients presenting to the emergency department (ED) with nonspecific complaints are difficult to accurately triage, risk stratify, and diagnose. This can delay appropriate treatment. The extent to which key medical outcomes are at all predictable in these patients, and which (if any) predictors are useful, has previously been unclear. To investigate these questions, we tested an array of statistical and machine learning models in a large group of patients and estimated the predictability of mortality (which occurred in 6.6% of our sample of patients), acute morbidity (58%), and presence of acute infectious disease (28.2%). METHODS: To investigate whether the best available tools can predict the three key outcomes, we fed data from a sample of 1,278 ED patients with nonspecific complaints into 17 state-of-the-art statistical and machine learning models. The patient sample stems from a diagnostic multicenter study with prospective 30-day follow-up conducted in Switzerland. Predictability of the three key medical outcomes was quantified by computing the area under the receiver operating characteristic curve (AUC) for each model. RESULTS: The models performed at different levels but, on average, the predictability of the target outcomes ranged between 0.71 and 0.82. The better models clearly outperformed physicians' intuitive judgments of how ill patients looked (AUC = 0.67 for mortality, 0.65 for morbidity, and 0.60 for infectious disease). CONCLUSIONS: Modeling techniques can be used to derive formalized models that, on average, predict the outcomes of mortality, acute morbidity, and acute infectious disease in patients with nonspecific complaints with a level of accuracy far beyond chance. The models also predicted these outcomes more accurately than did physicians' intuitive judgments of how ill the patients look; however, the latter was among the small set of best predictors for mortality and acute morbidity. These results lay the groundwork for further refining triage and risk stratification tools for patients with nonspecific complaints. More research, informed by whether the goal of a model is high sensitivity or high specificity, is needed to develop readily applicable clinical decision support tools (e.g., decision trees) that could be supported by electronic health records. PMID- 26375288 TI - Levels of sP-selectin and hs-CRP Decrease with Dietary Intervention with Selenium and Coenzyme Q10 Combined: A Secondary Analysis of a Randomized Clinical Trial. AB - BACKGROUND/OBJECTIVES: Inflammation and oxidative stress are central in many disease states. The major anti-oxidative enzymes contain selenium. The selenium intake in Europe is low, and supplementation with selenium and coenzyme Q10, important anti-oxidants, was evaluated in a previous study. The aim of this study was to evaluate response on the inflammatory biomarkers C-reactive protein, and sP-selectin, and their possible impact on cardiovascular mortality. SUBJECTS/METHODS: 437 elderly individuals were included in the study. Clinical examination, echocardiography, electrocardiography and blood samples were drawn. The intervention time was 48 months, and median follow-up was 5.2 years. The effects on inflammation/atherosclerosis were evaluated through analyses of CRP and sP-selectin. Evaluations of the effect of the intervention was performed using repeated measures of variance. All mortality was registered, and endpoints of mortality were assessed by Kaplan-Meier plots. RESULTS: The placebo group showed a CRP level of 4.8 ng/mL at the start, and 5.1 ng/mL at the study end. The active supplementation group showed a CRP level of 4.1 ng/mL at the start, and 2.1 ng/mL at the study end. SP-selectin exhibited a level of 56.6 mg/mL at the start in the placebo group and 72.3 mg/mL at the study end, and in the active group the corresponding figures were 55.9 mg/mL and 58.0 mg/mL. A significantly smaller increase was demonstrated through repeated measurements of the two biomarkers in those on active supplementation. Active supplementation showed an effect on the CRP and sP-selectin levels, irrespective of the biomarker levels. Reduced cardiovascular mortality was demonstrated in both those with high and low levels of CRP and sP-selectin in the active supplementation group. CONCLUSION: CRP and sP-selectin showed significant changes reflecting effects on inflammation and atherosclerosis in those given selenium and coenzyme Q10 combined. A reduced cardiovascular mortality could be demonstrated in the active group, irrespective of biomarker level. This result should be regarded as hypothesis-generating, and it is hoped it will stimulate more research in the area. PMID- 26375291 TI - Synthesis of the Tetrasaccharide Repeating Unit of the beta-Kdo-Containing Exopolysaccharide from Burkholderia pseudomallei and B. cepacia Complex. AB - The synthesis of the repeating unit of the immunogenic beta-Kdo-containing exopolysaccharide produced by Burkholderia pseudomallei and bacteria of the B. cepacia complex is described. The target tetrasaccharide was synthesized via stereoselective 1,2-cis- and 1,2-trans-galactosylations and beta-Kdosylation. A [3 + 1] coupling reaction between a trigalactosyl N-phenyl-2,2,2 trifluoroacetimidate donor and a Kdo acceptor has been successfully achieved for the assembly of the tetrasaccharide skeleton. PMID- 26375294 TI - How to retire with style. PMID- 26375296 TI - Reply: To PMID 25579641. PMID- 26375297 TI - Cell-Peptide Specific Interaction Can Inhibit Mycobacterium tuberculosis H37Rv Infection. AB - Studying proteins from the M. tuberculosis H37Rv envelop is important for understanding host-pathogen interaction regarding bacterial infection and survival within a host; such knowledge is indispensable regarding studies aimed at developing drugs or vaccines against tuberculosis, a disease which continues to cause more than one million deaths worldwide every year. The present work presents a study of the Rv3705c protein which has been described as being an outer protein. Several servers and bioinformatics' tools were used for predicting its location on mycobacterial surface and a 3D model of the protein was obtained which was then compared to experimental circular dichroism results for its peptides. PCR assays were used for corroborating rv3705c gene presence and transcription in a laboratory strain and immunoblotting and electron microscopy were used for confirming protein localisation on cell envelop. Receptor-ligand assays revealed two peptides having high specific binding (HABPs); peptide 38485 ((121)DRAFHRVVDRTVGTSGQTTA(140)) bound to both cell lines used as infection target (U937 and A549 epithelial cell line-derived macrophages) and 38488 ((181)RLRENVLLQAKVTQSGNAGP(200)) bound to U937 cells. It was found that peptide 38485 provided significant inhibition regarding mycobacterial entry to both cell lines in in vitro assays. These results led to proposing peptide 38485 as one of the epitopes to be used in future studies aimed at characterising the immune response of functionally important synthetic peptides which could be included in developing a synthetic anti-tuberculosis vaccine. PMID- 26375299 TI - Clinical Research Abstracts of the British Equine Veterinary Association Congress 2015. AB - REASONS FOR PERFORMING THE STUDY: Yellow fat disease or steatitis is characterised by a local or general inflammation of fat tissue and is occasionally found in horses. Diagnosis is challenging because of the wide range of nonspecific clinical signs. OBJECTIVES: To describe clinical signs, treatment, outcome and ultrasonographic findings in horses with steatitis. STUDY DESIGN: Retrospective study (January 2008 to January 2015). METHODS: History, clinical signs, ultrasonographic findings, diagnosis, treatment and outcome were recorded. RESULTS: Twenty cases (18 horses, 2 donkeys; 9 mares, 9 stallions, 2 geldings) were retrieved from 13,707 patient records. Mean age was 1.6 (+/- 0.8) years (range 1 month-3.5 years). All cases appeared between October and February except for one (August). History included dullness, recumbency, decreased appetite and weight loss. Fever, ventral oedema, stiff/painful gait and painful neck were found. Low haematocrit, low vitamin E and selenium and increased levels of creatinine kinase and particularly lactate dehydrogenase were almost consistent findings. On ultrasound, ventral oedema was found. Subperitoneal, perirenal, mesenteric, coronary and caudal mediastinal fat showed homogenously increased echogenicity. Especially the subperitoneal fat was surrounded by oedema or free fluid. Increased amounts of abdominal, thoracic and pericardial fluid were often found. Fat biopsies were taken in the neck or from the retroperitoneal fat in the ventral flank. In all horses where fat biopsy was taken (n = 13), steatitis was confirmed. Treatment consisted of selenium and vitamin E (intra-muscular injection followed by oral treatment) supplementation and anti-inflammatory treatment (dexamethasone or prednisolone parenteral or oral) for at least 1-4 weeks. Fourteen animals (70%) survived. Full recovery took about 2-6 months. CONCLUSIONS: Yellow fat disease may be underdiagnosed because of the nonspecific clinical signs. Ultrasound was extremely helpful for making a diagnosis. Recovery was rather slow but was achieved in 70% of the animals. Ethical animal research: Research ethics committee oversight not currently required by this conference: retrospective study of clinical records. Explicit owner informed consent for inclusion of animals in this study was not stated. SOURCE OF FUNDING: Ghent University (institutional). Competing interests: None declared. PMID- 26375298 TI - Fluorescence Based Characterization of Calcium Sensitizer Action on the Troponin Complex. AB - Calcium sensitizers enhance the transduction of the Ca(2+) signal into force within the heart and have found use in treating heart failure. However the mechanisms of action for most Ca(2+) sensitizers remain unclear. To address this issue an efficient fluorescence based approach to Ca(2+) sensitizer screening was developed which monitors cardiac troponin C's (cTnC's) hydrophobic cleft. This approach was tested on four common Ca(2+) -sensitizers, EMD 57033, levosimendan, bepridil and pimobendan with the aim of elucidating the mechanisms of action for each as well as proving the efficacy of the new screening method. Ca(2+) titration experiments were employed to determine the effect on Ca(2+) sensitivity and cooperativity of cTnC opening, while stopped flow experiments were used to investigate the impact on cTnC relaxation kinetics. Bepridil was shown to increase the sensitivity of cTnC for Ca(2+) under all reconstitution conditions, sensitization by the other drugs was context dependent. Levosimendan and pimobendan reduced the rate of cTnC closing consistent with a stabilization of cTnC's open conformation while bepridil increased the rate of relaxation. Experiments were also run on samples containing cTnT(T204E), a known Ca(2+) desensitizing phosphorylation mimic. Levosimendan, bepridil, and pimobendan were found to elevate the Ca(2+) -sensitivity of cTnT(T204E) containing samples in this context. PMID- 26375301 TI - Clinical Research Abstracts of the British Equine Veterinary Association Congress 2015. AB - REASONS FOR PERFORMING STUDY: Transcranial magnetic stimulation (TMS) is an electrophysiological technique used to elicit motor evoked potentials (MMEPs) to evaluate the functional integrity of the descending motor fibres in the spinal cord. Successful application of the technique was reported in horses with spinal cord compression. However, limited data are available on the correlation of TMS with histopathological changes. OBJECTIVES: To determine sensitivity of TMS for assessing the integrity of the spinal cord in horses with compressive lesions of the spinal cord. STUDY DESIGN: Case series. METHODS: The study was conducted on 6 horses with spinal ataxia grade III-V/V admitted to the Faculty of Veterinary Medicine, Ghent University. The horses underwent TMS, radiography of the cervical or thoracolumbar vertebral column, and myelography (4/6). All horses were subjected to euthanasia and the spinal cord examined histopathologically. RESULTS: In 5/6 horses MMEPs with abnormal onset latencies in both extensor carpi radialis muscles and cranial tibialis muscles were recorded, suggesting a cervical spinal cord lesion. Radiography revealed cervical vertebral malformation (4/5) with cervical vertebral canal stenosis (3/5) and tumour/osteomyelitis (1/5). In 1/6 horse MMEPs with normal onset latencies in extensor carpi radialis muscles and prolonged onset latencies in tibialis cranialis muscles were recorded, suggesting a thoracolumbar spinal cord lesion. Radiography revealed deformation of the 7th and 8th thoracic vertebrae. Myelography showed reduction in dural diameter and dorsal contrast column (4/4). Histopathological examination of the spinal cord confirmed compressive type lesions in all 6 horses with degenerative changes in the white matter of all funiculi, ballooning of myelin sheets, swollen axons, loss of axons and astroglial activation. CONCLUSIONS: In this case series abnormal function of descending motor pathways as registered by TMS showed 100% sensitivity with the histopathological characteristics of compressive lesions in the spinal cord, but the number of horses is limited and further research is warranted. Ethical animal research: Research ethics committee oversight not currently required by this conference: the study was performed on material collected during clinical procedures. Explicit owner informed consent for participation in this study was not stated. SOURCE OF FUNDING: Not applicable. Competing interests: None declared. PMID- 26375300 TI - Hypophosphorylation of ribosomal protein S6 is a molecular mechanism underlying ischemic tolerance induced by either hibernation or preconditioning. AB - Thirteen-lined ground squirrels (Ictidomys tridecemlineatus) have an extraordinary capacity to withstand prolonged and profound reductions in blood flow and oxygen delivery to the brain without incurring any cellular damage. As such, the hibernation torpor of I. tridecemlineatus provides a valuable model of tolerance to ischemic stress. Herein, we report that during hibernation torpor, a marked reduction in the phosphorylation of the ribosomal protein S6 (rpS6) occurs within the brains of I. tridecemlineatus. Of note, rpS6 phosphorylation was shown to increase in the brains of rats that underwent an occlusion of the middle cerebral artery. However, such an increase was attenuated after the implementation of an ischemic preconditioning paradigm. In addition, cultured cortical neurons treated with the rpS6 kinase (S6K) inhibitors, D-glucosamine or PF4708671, displayed a decrease in rpS6 phosphorylation and a subsequent increase in tolerance to oxygen/glucose deprivation, an in vitro model of ischemic stroke. Collectively, such evidence suggests that the down-regulation of rpS6 signal transduction may account for a substantial part of the observed increase in cellular tolerance to brain ischemia that occurs during hibernation torpor and after ischemic preconditioning. Further identification and characterization of the mechanisms used by hibernating species to increase ischemic tolerance may eventually clarify how the loss of homeostatic control that occurs during and after cerebral ischemia in the clinic can ultimately be minimized and/or prevented. Mammalian hibernation provides a valuable model of tolerance to ischemic stress. Herein, we demonstrate that marked reductions in the phosphorylation of ribosomal protein S6 (rpS6), extracellular signal-regulated kinase family of mitogen-activated protein (MAP) kinase p44/42 (p44/42MAPK) and ribosomal protein S6 kinase (S6K) occur within the brains of both hibernating squirrels and rats, which have undergone an ischemic preconditioning paradigm. We therefore propose that the down-regulation of rpS6 signal transduction may account for a substantial part of the observed increase in cellular tolerance to brain ischemia that occurs during hibernation torpor and after ischemic preconditioning, via a suppression of protein synthesis and/or energy consumption. PMID- 26375302 TI - Preparation of Chitosan-Alginate Nanoparticles for Trans-cinnamaldehyde Entrapment. AB - Trans-cinnamaldehyde incorporated chitosan-alginate nanoparticles were synthesized using the ionic gelation and polyelectrolyte complexation technique. Alginate, chitosan, calcium chloride, and trans-cinnamaldehyde at predetermined concentrations were complexed electrostatically to optimize particle size and loading efficiency. A final methodology using optimized processing parameters (for example, stirring time, homogenization time, equilibration time, and droplet size) was developed. The best working alginate to chitosan mass ratio was determined to be 1.5:1 at a pH dispersion of 4.7. Particle size (166.26 nm) and encapsulation efficiency (73.24%) were further optimized at this mass ratio using an alginate:calcium chloride mass ratio of 4.8:1, alginate:trans-cinnamaldehyde mass ratio of 37.5:1, a 18 gauge syringe needle, stirring times of 90 min, 15 min of homogenization at 21000 rpm, and equilibration time of 24 h. Optimized nanoparticles showed increased stability (6 wk) and translucency in solution. The final radical scavenging effect of loaded particles in apple juice was 62% and trans-cinnamaldehyde was just as available to react in free form as it was in inclusion complexes. The final nanoparticle system with modified and optimized processing parameters reduced the size by 43.6% and increased entrapment efficiency by 17.2%. Nanoparticles resembled a spherical shell and core type arrangement (that is, spherical, distinct, and regular) and were in the size range of 10 to 100 nm. PRACTICAL APPLICATION: Nanoencapsulation of lipophilic antimicrobial and antioxidant compounds has the potential to improve their effectiveness and efficiency of delivery in food systems. Determining a standard nanoparticle synthesis methodology and optimizing entrapment efficiency and particle size prior to characterization studies allows for improved understanding of nanosystems and substantiates results. This study demonstrates the potential to improve current nanoparticle preparation techniques to fine tune critical physical parameters. The results presented in this study can aid in developing new and simple ways to improve nanoparticle formulations and prompt further studies to validate entrapment of lipophilic compounds combinations. PMID- 26375303 TI - Successful Treatment of Congenital Erythroleukemia With Low-Dose Cytosine Arabinoside. PMID- 26375304 TI - Squeeze flow rheometry as a novel tool for the characterization of highly concentrated protein solutions. AB - This study aims at defining rheological parameters for the characterization of highly concentrated protein solutions. As a basis for comparing rheological behavior with protein solution characteristics the protein phase behavior of Lysozyme from chicken egg white with concentrations up to 225 mg/mL, changing pH values and additive concentrations was studied in a microbatch scale format. The prepared phase diagrams, scored after 40 days (t40) give insights into the kind and kinetics of the phase transitions that occur. Oscillatory frequency sweep measurements of samples with exactly the same conditions were conducted immediately after preparation (t0). The protein solutions behave viscoelastic and show a characteristic curve shape of the storage modulus (G') and the loss modulus (G"). The graphs provide information about the cross-linking degree of the respective sample. The measured rheological parameters were sensitive concerning solution composition, protein concentration and solution inner structure. The rheological moduli G' and G" and especially the ratio of these parameters over a frequency range from 100 to 40000 rad/sec give information about the aggregation tendency of the protein under tested conditions. We succeeded to correlate protein phase behavior with the defined rheological key parameter omegaCO. This point represents the frequency value of the intersection point from G' and G". In our study Lysozyme expressed a omegaCO threshold value of 20000 rad/sec as a lower limit for stable protein solutions. The predictability of lysozyme aggregation tendency and crystallization by means of squeeze flow rheometry is shown. PMID- 26375305 TI - Lymphedema: A General Outline of Its Anatomical Base. AB - The anatomic research of the lymphatic system has been a very controversial subject throughout due to the complexity of the methods for its visualization. More than 30 years ago, together with Prof. Caplan, we began the vascular anatomy research, focusing on the lymphatic anatomy, developing and adapting different techniques of injection. On the third Normal Anatomy Chair of Buenos Aires University, we summarized the lymphatic drainage of the breast and the limbs to interpret the anatomic bases of lymphedema. PMID- 26375306 TI - Bleeding spectrum in children with moderate or severe von Willebrand disease: Relevance of pediatric-specific bleeding. AB - The bleeding phenotype of children with von Willebrand disease (VWD) needs to be characterized in detail to facilitate diagnosis during childhood and aid in the planning and assessment of treatment strategies. The objective was to evaluate the occurrence, type, and severity of bleeding in a large cohort of children with moderate and severe VWD. We included 113 children (aged 0-16 years) with Type 1 (n = 60), 2 (n = 44), and 3 (n = 9) VWD with von Willebrand factor (VWF) antigen and/or VWF ristocetin cofactor levels <= 30 U/dL from a nation-wide cross sectional study ("Willebrand in the Netherlands" study). Bleeding severity and frequency were determined using the International Society on Thrombosis and Hemostasis-Bleeding Assessment Tool (ISTH-BAT) with supplementary pediatric specific bleeding symptoms (umbilical stump bleeding, cephalohematoma, cheek hematoma, conjunctival bleeding, postcircumcision and postvenipuncture bleeding). We found that all 26 postmenarche girls experienced menorrhagia. Other common bleedings were cutaneous (81%), oropharyngeal (64%), prolonged bleeding from minor wounds (58%), and epistaxis (56%). Pediatric-specific bleeding symptoms were present in 44% of patients. ISTH-BAT bleeding score was higher in index cases than in affected family members (median, 12.0 vs. 6.5, P < 0.001), higher in Type 3 VWD than in Type 2 or 1 (17.0 vs. 10.5 or 6.5, P < 0.001) and higher in children with severe (<10 U/dL) than moderate VWD (10-30 U/dL) (11.0 vs. 7.0, P < 0.001). Frequency of any bleeding, epistaxis, and oral cavity was higher in types 2 and 3 than in Type 1 VWD and was associated with VWF levels. We conclude that pediatric-specific bleeding symptoms occurred in a large proportion of children with moderate or severe VWD and should be included when evaluating children for VWD. PMID- 26375307 TI - Distinct Enzyme-Substrate Interactions Revealed by Two Dimensional Kinetic Comparison between Dehaloperoxidase-Hemoglobin and Horseradish Peroxidase. AB - The time-resolved kinetics of substrate oxidation and cosubstrate H2O2 reduction by dehaloperoxidase-hemoglobin (DHP) on a seconds-to-minutes time scale was analyzed for peroxidase substrates 2,4,6-tribromophenol (2,4,6-TBP), 2,4,6 trichlorophenol (2,4,6-TCP), and ABTS. Substrates 2,4,6-TBP and 2,4,6-TCP show substrate inhibition at high concentration due to the internal binding at the distal pocket of DHP, whereas ABTS does not show substrate inhibition at any concentration. The data are consistent with an external binding site for the substrates with an internal substrate inhibitor binding site for 2,4,6-TBP and 2,4,6-TCP. We have also compared the kinetic behavior of horseradish peroxidase (HRP) in terms of kcat, Km(AH2) and Km(H2O2) using the same kinetic scheme. Unlike DHP, HRP does not exhibit any measurable substrate inhibition, consistent with substrate binding at the edge of heme near the protein surface at all substrate concentrations. The binding of substrates and their interactions with the heme iron were further compared between DHP and HRP using a competitive fluoride binding experiment, which provides a method for quantitative measurement of internal association constants associated with substrate inhibition. These experiments show the regulatory role of an internal substrate binding site in DHP from both a kinetic and competitive ligand binding perspective. The interaction of DHP with substrates as a result of internal binding actually stabilizes that protein and permits DHP to function under conditions that denature HRP. As a consequence, DHP is a tortoise, a slow but steady enzyme that wins the evolutionary race against the HRP-type of peroxidase, which is a hare, initially rapid, but flawed for this application because of the protein denaturation under the conditions of the experiment. PMID- 26375308 TI - Selective Reminding and Free and Cued Selective Reminding in Mild Cognitive Impairment and Alzheimer Disease. AB - The Selective Reminding Test (SRT) and the Free and Cued Selective Reminding Test (FCSRT) are multitrial memory tests that use a common "selective reminding" paradigm that aims to facilitate learning by presenting only the missing words from the previous recall trial. While in the FCSRT semantic cues are provided to elicit recall, in the SRT, participants are merely reminded of the missing items by repeating them. These tests have been used to assess age-related memory changes and to predict dementia. The performance of healthy elders on these tests has been compared before, and results have shown that twice as many words were retrieved from long-term memory in the FCSRT compared with the SRT. In this study, we compared the tests' properties and their accuracy in discriminating amnestic mild cognitive impairment (aMCI; n = 20) from Alzheimer disease (AD; n = 18). Patients with AD performed significantly worse than patients with aMCI on both tests. The percentage of items recalled during the learning trials was significantly higher for the FCSRT in both groups, and a higher number of items were later retrieved, showing the benefit of category cueing. Our key finding was that the FCSRT showed higher accuracy in discriminating patients with aMCI from those with AD. PMID- 26375309 TI - Reprogramming aging through DOT1L inhibition. PMID- 26375318 TI - Abortion Context and Women's Contraceptive Use. PMID- 26375320 TI - Effects of artificial light at night on human health: A literature review of observational and experimental studies applied to exposure assessment. AB - It has frequently been reported that exposure to artificial light at night (ALAN) may cause negative health effects, such as breast cancer, circadian phase disruption and sleep disorders. Here, we reviewed the literature assessing the effects of human exposure to ALAN in order to list the health effects of various aspects of ALAN. Several electronic databases were searched for articles, published through August 2014, related to assessing the effects of exposure to ALAN on human health; these also included the details of experiments on such exposure. A total of 85 articles were included in the review. Several observational studies showed that outdoor ALAN levels are a risk factor for breast cancer and reported that indoor light intensity and individual lighting habits were relevant to this risk. Exposure to artificial bright light during the nighttime suppresses melatonin secretion, increases sleep onset latency (SOL) and increases alertness. Circadian misalignment caused by chronic ALAN exposure may have negative effects on the psychological, cardiovascular and/or metabolic functions. ALAN also causes circadian phase disruption, which increases with longer duration of exposure and with exposure later in the evening. It has also been reported that shorter wavelengths of light preferentially disturb melatonin secretion and cause circadian phase shifts, even if the light is not bright. This literature review may be helpful to understand the health effects of ALAN exposure and suggests that it is necessary to consider various characteristics of artificial light, beyond mere intensity. PMID- 26375321 TI - ECO-physiological response of S. vulgaris to CR(VI): Influence of concentration and genotype. AB - The objective of this work is to study the response of Silene vulgaris to a range of environmentally relevant concentrations of Cr(VI) in order to evaluate its potential use in the phytomanagement of Cr polluted sites. Cuttings of six homogenous genotypes from Madrid (Spain) have been used as plant material. The eco-physiological response of S. vulgaris to Cr(VI) changed with the genotype. The yield dose-response curve was characterized by stimulation at low doses of Cr(VI). The effects of metal concentration were quantified on root dry weight, water content and chlorophyll content, determined by SPAD index. The response was not homogeneous for all studied genotypes. At high doses of Cr(VI), plants increased micronutrient concentration in dry tissues which suggested that nutrient balance could be implicated in the alleviation of Cr toxicity. This work highlights the importance of studying the eco-physiological response of metallophytes under a range of pollutant concentrations to determine the most favorable traits to be employed in the phytomanagement process. PMID- 26375322 TI - Computed Tomography Is More Sensitive than Ultrasound for the Diagnosis of Acute Cholecystitis. AB - BACKGROUND: Ultrasound (US) is the first-line diagnostic study for evaluating gallstone disease and is considered the test of choice for diagnosing acute cholecystitis (AC). However, computed tomography (CT) is used widely for the evaluation of abdominal pain and is often obtained as a first abdominal imaging test, particularly in cases in which typical clinical signs of AC are absent or other possible diagnoses are being considered. We hypothesized that CT is more sensitive than US for diagnosing AC. METHODS: A prospective registry of all urgent cholecystectomies performed by our acute care surgery service between June 2008 and January 2014 was searched for cases of AC. The final diagnosis was based on operative findings and pathology. Patients were classified into two groups according to pre-operative radiographic work-up: US only or CT and US. The US group was compared with the CT and US group with respect to clinical and demographic characteristics. For patients undergoing both tests the sensitivity of the two tests was compared. RESULTS: One hundred one patients with AC underwent both US and CT. Computed tomography was more sensitive than US for the diagnosis of AC (92% versus 79%, p=0.015). Ultrasound was more sensitive than CT for identification of cholelithiasis (87% versus 60%, p<0.01). Patients undergoing both tests prior to surgery were more likely to be older, male, have medical comorbidities, and lack typical clinical signs of AC. CONCLUSIONS: Computed tomography is more sensitive than US for the diagnosis of AC and is most often used in patients without typical clinical signs of AC. PMID- 26375324 TI - Attitudes toward Substance Abuse Clients: An Empirical Study of Clinical Psychology Trainees. AB - Despite the high prevalence of substance use disorder (SUD) and its frequent comorbidity with mental illness, individuals with SUD are less likely to receive effective SUD treatment from mental health practitioners than SUD counselors. Limited competence and interest in treating this clinical population are likely influenced by a lack of formal training in SUD treatment. Using a factorial survey-vignette design that included three clinical vignettes and a supplementary survey instrument, we investigated whether clinical psychology doctoral students differ in their level of negative emotional reactions toward clients with SUD versus major depressive disorder (MDD); whether they differ in their attributions for SUD versus MDD; and how their negative emotional reactions and attributions impact their interest in pursuing SUD clinical work. Participants were 155 clinical psychology graduate-level doctoral students (72% female). Participants endorsed more negative emotional reactions toward clients with SUD than toward clients with MDD. They were also more likely to identify poor willpower as the cause for SUD than for MDD. More than a third reported interest in working with SUD populations. Highest levels of interest were associated with prior professional and personal experience with SUD, four to six years of clinical experience, and postmodern theoretical orientation. PMID- 26375323 TI - Symptoms, signs, and tests: The general practitioner's comprehensive approach towards a cancer diagnosis. AB - OBJECTIVE: To study the relative importance of different tools a GP can use during the diagnostic process towards cancer detection. DESIGN: Retrospective cohort study with prospective registration of cancer in general practice. SETTING AND SUBJECTS: One hundred and fifty-seven Norwegian general practitioners (GPs) reported 261 cancer patients. METHOD: During 10 consecutive days, GPs registered all patient consultations and recorded any presence of seven focal symptoms and three general symptoms, commonly considered as warning signs of cancer (WSC). Follow-up was done six to 11 months later. For each patient with new or recurrent cancer, the GP completed a questionnaire with medical-record-based information concerning the diagnostic procedure. RESULTS: In 78% of cancer cases, symptoms, signs, or tests helped diagnose cancer. In 90 cases, there were 131 consultation recorded WSC that seemed related to the cancer. Further symptoms were reported for another 74 cases. Different clinical signs were noted in 41 patients, 16 of whom had no previous recording of symptoms. Supplementary tests added information in 59 cases; in 25 of these there were no recordings of symptoms or signs. Sensitivity of any cancer-relevant symptom or clinical finding ranged from 100% for patients with uterine body cancer to 57% for patients with renal cancer. CONCLUSION: WSC had a major role as initiator of a cancer diagnostic procedure. Low-risk-but-not-no-risk symptoms also played an important role, and in 7% of patients they were the only symptoms. Clinical findings and/or supplementary procedures were sometimes decisive for rapid referral. PMID- 26375325 TI - The role of age in intracerebral hemorrhages. AB - We aimed to identify the role of age in intracerebral hemorrhage (ICH), as well as characterize the most commonly used age cut off points in the literature, with the hope of understanding and guiding treatment. Strokes are one of the leading causes of death in the USA, and ICH is the deadliest type. Age is a strong risk factor, but it also affects the body in numerous ways, including changes to the cardiovascular and central nervous systems that interplay with the multiple risk factors for ICH. Understanding the role of age in risk and outcomes of ICH can guide treatment and future clinical trials. A current review of the literature suggests that the age cut offs for increased rates of mortality and morbidity vary from 60-80 years of age, with the most common age cut offs being at 65 or 70 years of age. In addition to age as a determinant of ICH outcomes, age has its own effects on the maturing body in terms of changes in physiology, while also increasing the risk of multiple chronic health conditions and comorbidities, including hypertension, diabetes, and anticoagulant treatment for atrial fibrillation, all of which contribute to the pathology of ICH. The interaction of these chronic conditions, changes in physiology, age, and ICH is evident. However, the exact mechanism and extent of the impacts remains unclear. The ambiguity of these connections may be further obscured by individual patient preferences, and there are limitations in the literature which guides the current recommendations for aging patients. PMID- 26375326 TI - Intracranial involvement of posttransplant lymphoproliferative disorder multiple myeloma. AB - We report a 61-year-old man with intracranial multiple myeloma (MM) presenting as a posttransplant lymphoproliferative disorder (PTLD) following a kidney transplant. Two months after his transplant, the man developed acute rejection with Epstein-Barr virus (EBV) viremia, requiring aggressive immunosuppression. Twenty months following transplantation, the patient presented with multiple neurologic deficits. Imaging revealed numerous lytic lesions in the skull, most conspicuously a 4.1cm right frontal skull mass with prominent intracranial extension. Histologic sections of the frontal bone lesion showed sheets of atypical plasma cells that were positive for CD138 and kappa immunoglobulin light chains. Chromogenic in situ hybridization for EBV-encoded small RNA was also positive. Plasma cell neoplasms, either as MM or a plasmacytoma, are one of the least common forms of PTLD, and their rarity limits the possibility of major studies to detail their behavior. Most often seen after renal transplantation, the majority are EBV-driven, similarly to other PTLD. While studies have demonstrated several risk factors, behavior and optimal management of PTLD plasma cell neoplasms are unknown. Plasma cell neoplasms affect the nervous system in a variety of ways but rarely via intracranial disease. MM usually presents initially with several classic signs and symptoms, but our patient's presentation was typical of a localized brain tumor with generalized and focal gross neurologic defects. PMID- 26375327 TI - Reengineering cyt b562 for hydrogen production: A facile route to artificial hydrogenases. AB - Bioinspired, protein-based molecular catalysts utilizing base metals at the active are emerging as a promising avenue to sustainable hydrogen production. The protein matrix modulates the intrinsic reactivity of organometallic active sites by tuning second-sphere and long-range interactions. Here, we show that swapping Co-Protoporphyrin IX for Fe-Protoporphyrin IX in cytochrome b562 results in an efficient catalyst for photoinduced proton reduction to molecular hydrogen. Further, the activity of wild type Co-cyt b562 can be modulated by a factor of 2.5 by exchanging the coordinating methionine with alanine or aspartic acid. The observed turnover numbers (TON) range between 125 and 305, and correlate well with the redox potential of the Co-cyt b562 mutants. The photosensitized system catalyzes proton reduction with high efficiency even under an aerobic atmosphere, implicating its use for biotechnological applications. This article is part of a Special Issue entitled Biodesign for Bioenergetics--the design and engineering of electronic transfer cofactors, proteins and protein networks, edited by Ronald L. Koder and J.L. Ross Anderson. PMID- 26375328 TI - Role of interleukin-32 in the mechanism of chronic inflammation in IgG4-related disease and as a predictive biomarker for drug-free remission. AB - OBJECTIVES: In immunoglobulin (Ig) G4-related disease (IgG4-RD), the mechanism of chronic inflammation and predictive factors for drug-free remission is still unclear. To examine the issues, we focused on tuberculosis, a chronic infection, and on the role of interleukin (IL)-32. METHODS: We examined the positive rate of QuantiFERON TB-2G (QFT-2G) in 126 patients with IgG4-RD, and compared with the rate in the general population. Furthermore, specimens of submandibular glands from the maintenance treatment group and drug-free group of IgG4-RD and specimens of small salivary glands from primary Sjogren's syndrome (SS) were stained with anti-IL-32 antibody and anti-protease-activated receptor 2 antibody, and the number of positive cells was compared between these groups. RESULTS: The positive rate of QFT-2G was 19.8% in IgG4-RD patients, which is higher than in the general population. The expression of IL-32 and PAR2 in the submandibular glands of the maintenance treatment group of IgG4-RD was significantly greater than that of the drug-free remission group and SS patients. CONCLUSIONS: This study indicates the possibility that IL-32 is associated with chronic inflammation and that it can be a predictive factor for drug-free remission in IgG4-RD. PMID- 26375329 TI - Toward Individualized Neurosurgery: Quantifying Arteriovenous Malformation Embolization with Magnetic Resonance Angiography. PMID- 26375330 TI - Human factors approach to evaluate the user interface of physiologic monitoring. AB - BACKGROUND: As technology infiltrates more of our personal and professional lives, user expectations for intuitive design have driven many consumer products, while medical equipment continues to have high training requirements. Not much is known about the usability and user experience associated with hospital monitoring equipment. This pilot project aimed to better understand and describe the user interface interaction and user experience with physiologic monitoring technology. DESIGN: This was a prospective, descriptive, mixed-methods quality improvement project to analyze perceptions and task analyses of physiologic monitors. METHODS: Following a survey of practice patterns and perceived abilities to accomplish key tasks, 10 voluntary experienced physician and nurse subjects were asked to perform a series of tasks in 7 domains of monitor operations on GE Monitoring equipment in a single institution. For each task analysis, data were collected on time to complete the task, the number of button pushes or clicks required to accomplish the task, economy of motion, and observed errors. RESULTS: Although 60% of the participants reported incorporating monitoring data into patient care, 80% of participants preferred to receive monitoring data at the point of care (bedside). Average perceived central station usability is 5.3 out of 10 (ten is easiest). CONCLUSIONS: High variability exists in monitoring station interaction performance among those participating in this project. Alarms were almost universally silenced without cognitive recognition of the alarm state. Education related to monitoring operations appeared largely absent in this sample. Most users perceived the interface to not be intuitive, complaining of multiple layers and steps for data retrieval. These clinicians report real-time monitoring helpful for abrupt changes in condition like arrhythmias; however, reviewing alarms is not prioritized as valuable due to frequent false alarms. Participants requested exporting monitoring data to electronic medical records. Much research is needed to develop best practices for display of real-time information, organization and filtering of meaningful data, and simplified ways to find information. PMID- 26375331 TI - Elucidating the evolutionary relationships of the Aiptasiidae, a widespread cnidarian-dinoflagellate model system (Cnidaria: Anthozoa: Actiniaria: Metridioidea). AB - Sea anemones of the family Aiptasiidae sensu Grajales and Rodriguez (2014) are conspicuous members of shallow-water environments, including several species widely used as model systems for the study of cnidarian-dinoflagellate symbiosis and coral bleaching. Although previously published phylogenetic studies of sea anemones recovered Aiptasiidae as polyphyletic, they only included a sparse sample in terms of its taxonomic diversity and membership of the family had not been yet revised. This study explores the phylogenetic relationships of this family using five molecular markers and including newly collected material from the geographical distribution of most of the currently described genera and species. We find a monophyletic family Aiptasiidae. All the currently proposed genera were recovered as monophyletic units, a finding also supported by diagnostic morphological characters. Our results confirm Bellactis and Laviactis as members of Aiptasiidae, also in agreement with previous morphological studies. The monophyly of the group is congruent with the morphological homogeneity of the members of this family. The obtained results also allow discussing the evolution of morphological characters within the family. Furthermore, we find evidence for and describe a new cryptic species, Exaiptasia brasiliensis sp. nov., based on molecular data, geographical distribution, and the identity of its endosymbiotic dinoflagellate. PMID- 26375332 TI - Limbal transplantation at a tertiary hospital in Brazil: a retrospective study. AB - PURPOSE: Epidemiological analysis of limbal transplantation surgeries performed in the Ophthalmologic Hospital of Sorocaba. METHODS: Retrospective medical records review of 30 patients who underwent limbal stem cell transplants between January 2003 and March 2008. Cases involving conjunctival limbal autograft were classified as group I, and those involving conjunctival limbal allograft as group II. RESULTS: Two patients were excluded due to incomplete data during postoperative follow-up. Of the total sample of 28 patients, 53.6% constituted group I, whereas 46.4% were included in group II. Males were predominant (67.9%), and right eyes were the most prevalent (67.9%). The mean age was 40.3 years. Unilateral cases accounted for 60.7%. The most frequent pathology causing limbal system failure was chemical burns (53%). The mean length of time from diagnosis to surgery was 11.18 years. The limbal graft and amniotic membrane were associated in 75% of all cases, and tarsorrhaphy in 57.1%. The average follow-up period was 24.84 months. The uncorrected visual acuity improved in 38% of the cases, was unchanged in 28.5%, and deteriorated in 33.3%. There was no persistent epithelial defect in 75% of the patients. The conjunctivalization rate was similar between the groups (53.3% and 58.3%, respectively). The transparency improved in only 38.4% of the cases, and 28.5% of the surgeries performed were successful. The most prevalent complication was persistent epithelial defect, which occurred in 25% of the patients, followed by corneal melting in 14.2%. Other complications observed included infectious ulcers, limbal graft necrosis or ischemia, perforation, and descemetocele. CONCLUSION: Chemical burns remain the main cause of limbal stem cell deficiency. In these cases, limbal transplantation is the standard procedure to restore the ocular surface even though the success rate is low. PMID- 26375333 TI - Intrastromal corneal ring segment implantation for ectasia after refractive surgery. AB - PURPOSE: To evaluate the clinical outcomes of intrastromal corneal ring segment (ICRS) implantation to correct ectasia in eyes with prior refractive surgery. METHODS: Forty-one eyes of 25 patients (13 men, 12 women; mean age, 28.66 years) with ectasia after refractive surgery [photorefractive keratectomy (PRK) or laser in situ keratomileusis (LASIK)] were included in a nonrandomized, retrospective, observational case series. Corneal tunnels were created by mechanical dissection in all eyes. Main outcome measures included uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BCVA), refraction, keratometry, and computerized analysis of corneal topography. Patients were divided into two groups by the type of refractive surgery (Group A: PRK, Group B: LASIK). RESULTS: The mean preoperative manifest astigmatism decreased from -1.88 to -0.84 D in Group A (p=0.096) and -3.18 to -1.77 D in Group B (p=0.000). The mean keratometric astigmatism decreased from -2.58 to -1.66 D in Group A (p=0.010) and -4.80 to -2.78 D in Group B (p=0.000). The mean spherical equivalent decreased from -2.97 to -2.05 D in Group A (p=0.065) and -3.31 to -2.42 D in Group B (p=0.014). No significant between-group differences were noted on the comparison of preoperative and postoperative results. No intraoperative or postoperative complications were observed. CONCLUSION: ICRS implantation is a useful treatment option for ectasia following refractive surgery, and it has significantly reduced the refractive cylinder and increased best spectacle-corrected visual acuity. PMID- 26375334 TI - Local treatment of toxoplasmic retinochoroiditis with intravitreal clindamycin and dexamethasone. AB - PURPOSE: To report the clinical outcomes of local treatment of toxoplasmic retinochoroiditis (TRC) with intravitreal injections of clindamycin and dexamethasone. METHODS: STUDY POPULATION: 16 eyes (16 patients) with active TRC sparing the macula and juxtapapillary area treated with intravitreal injections of clindamycin (1 mg) and dexamethasone (1 mg) without concomitant systemic antitoxoplasmic or anti-inflammatory therapy. Measured parameters: Best-corrected visual acuity (BCVA) was measured by an Early Treatment Diabetic Retinopathy Study (ETDRS) chart. BCVA and clinical characteristics of retinochoroiditis were assessed at baseline and at 1, 3, 6, and 12 months. PRIMARY OUTCOME MEASURES: Resolution of retinochoroiditis and changes in BCVA. RESULTS: Control of TRC was achieved in all cases with a mean interval of 2.48 +/- 1.03 weeks (2-6 weeks). A single injection of intravitreal clindamycin and dexamethasone was performed in 12 patients, and four patients required two intravitreal injections, during the follow-up period. Fourteen eyes (87.5%) improved >= 2 ETDRS lines of BCVA, of two or more Early Treatment Diabetic Retinopathy Study lines, BCVA remained stable in two eyes (12.5%), and no patient had decreased BCVA at the end of the follow-up period. No ocular or systemic adverse events were observed. CONCLUSION: Local treatment with intravitreal injections of clindamycin and dexamethasone without concomitant systemic therapy was associated with resolution of TRC in patients without macular or juxtapapillary involvement. Intravitreal clindamycin and dexamethasone may represent a viable treatment option in patients with allergies or inadequate responses to oral medications. PMID- 26375335 TI - The influence of size and shape of Nd:YAG capsulotomy on visual acuity and refraction. AB - PURPOSE: To evaluate the influence of size and shape of neodymium:yttrium aluminum- Garnet (Nd:YAG) laser capsulotomy on visual acuity and refraction. METHODS: We retrospectively evaluated 85 eyes of 67 patients treated with Nd:YAG laser posterior capsulotomy for posterior capsule opacification (PCO). The mean age of included patients was 57.57 +/- 9.26 (mean +/- standard deviation, 38-75 years). The mean interval between surgery and Nd:YAG laser capsulotomy was 26.09 +/- 7.08 (10-38) months. Patients were divided into four groups according to the shape and size of capsulotomy. Groups comprised patients with cruciate shape capsulotomies with openings of less than or equal to 3.5 mm (Group 1) or greater (Group 2) and patients with circular shape capsulotomies with openings of less than or equal to 3.5 mm (Group 3) or greater (Group 4). RESULTS: The mean number and energy of laser firings were significantly higher in Group 4 (p=0.00), and significantly lower in Group 1 (p=0.00), compared with that in other groups. Pre procedural and post-procedural mean spherical equivalent (SE) values were significantly higher in Group 1 (p=0.026 and p=0.011, respectively). No statistical difference in best-corrected visual acuities (BCVA) or intraocular pressures (IOP) were observed between groups before (p=0.44 and p=0.452, respectively) or after capsulotomy (p=0.108 and p=0.125, respectively). A significantly higher number of patients in Group 4 (p=0.001), and a significantly lower number of patients in Group 1 (p=0.001), reported floating bodies compared with that in other groups. No significant changes in SE or intraocular pressure were observed after capsulotomy in any group (p=0.074 and p=0.856, respectively). Best-corrected visual acuity was significantly improved following capsulotomy in all groups (p<0.01). CONCLUSION: Cruciate shape capsulotomy with an opening of 3.5 mm or less provides the greatest improvement in visual function with minimal complications. PMID- 26375336 TI - Vision-related quality of life in children with retinopathy of prematurity. AB - PURPOSE: To evaluate the effect of retinopathy of prematurity (ROP) on vision related quality of life in children. METHODS: The Children's Visual Function Questionnaire (CVFQ), an instrument that evaluates vision-related quality of life in children, was used. It is divided into 6 subscales: General Health, Vision Health, Competence, Personality, Family Impact, and Treatment. The sample consisted of parents of premature children up to 3 years of age who had ROP and no neurological damage (ROP group) and parents of premature children up to 3 years of age who had normal vision and absence of other diseases (control group). RESULTS: There were 88 subjects in total, 43 in the ROP group and 45 in the control group. The ROP group had lower scores on the CVFQ than the control group. The Total Index and all CVFQ subscale scores and for were significant lower in the ROP group than in the control group. The ROP group was divided according to the severity of the disease. The Total Index, Vision Health, and Competence scores in children with more severe ROP were significantly lower than those in children with less severe ROP. CONCLUSION: ROP was shown to have a negative effect on vision-related quality of life in children. PMID- 26375338 TI - Influence of the blood glucose level on the development of retinopathy of prematurity in extremely premature children. AB - PURPOSE: To investigate the influence of the blood glucose level on the development of retinopathy of prematurity (ROP) in extremely premature infants. METHODS: Sixty-four premature infants with a gestational age of less than 30 weeks and a birth weight of less than 1500 g were included in the study. Children without ROP were allocated to Group 1 (n=14, gestational age 28.6 +/- 1.4 weeks, birth weight 1162 +/- 322 g), and children with spontaneous regression of ROP were allocated to Group 2 (n=32, gestational age 26.5 +/- 1.2 weeks, birth weight 905 +/- 224 g). Children with progressive ROP who underwent laser treatment were included in Group 3 (n=18, gestational age 25.4 +/- 0.7 weeks, birth weight 763 +/- 138 g). The glucose level in the capillary blood of the premature infants was monitored daily during the first 3 weeks of life. A complete ophthalmological screening was performed from the age of 1 month. The nonparametric signed-rank Wilcoxon-Mann-Whitney test was used for statistical analysis. RESULTS: The mean blood glucose level was 7.43 +/- 2.6 mmol/L in Group 1, 7.8 +/- 2.7 mmol/L in Group 2, and 6.7 +/- 2.6 mmol/L in Group 3. There were no significant differences in the blood glucose levels between children with and without ROP, and also between children with spontaneously regressing ROP and progressive ROP (p>0.05). Additionally, there were no significant differences in the blood glucose levels measured at the first, second, and third weeks of life (p>0.05). CONCLUSION: The blood glucose level is not related to the development of ROP nor with its progression or regression. The glycemic level cannot be considered as a risk factor for ROP, but reflects the severity of newborns' somatic condition and morphofunctional immaturity. PMID- 26375337 TI - Investigation of the association between glaucoma and Helicobacter pylori infection using the 14C-urea breath test. AB - PURPOSE: To investigate the association between glaucoma and Helicobacter pylori infection by evaluating for the presence of H. pylori infection in patients with glaucoma using the 14C-urea breath test (14C-UBT). METHODS: Using 14C-UBT, H. pylori infection positivity was compared between a group of patients with primary open-angle glaucoma and a control group with normal intraocular pressure and a normal optic disc or normal perimetry. RESULTS: The 14C-UBT was positive in 18 (51.42%) out of 35 patients in the glaucoma group and in 15 (42.85%) out of 35 patients in the control group. H. pylori infection positivity rates were similar between the glaucoma and control groups (p>0.05). CONCLUSION: According to the 14C-UBT, there is no association between primary open-angle glaucoma and H. pylori infection. PMID- 26375340 TI - Optical coherence tomography in patients undergoing cataract surgery. AB - PURPOSE: To assess the ability of spectral domain optical coherence tomography (SD-OCT) to diagnose macular changes pre- and post-cataract surgery and to identify changes in central foveal thickness (CFT) relative to age, sex, and presence of concomitant ophthalmic pathologies, for a period of 6 months post surgery. METHODS: A prospective study of patients evaluated by SD-OCT within 5 h before surgery at 7, 30, 60, 90, and 180 days post-op, with respect to CFT and presence of maculopathy. RESULTS: Ninety-eight eyes of 98 patients were evaluated, with the following mean results: age = 71.4 years, pre-op VA = 0.27 logMAR, and final VA = 0.73 logMAR. There were 21 eyes in patients with diabetes mellitus (DM) and 10 eyes with age-related macular degeneration (AMD), three with epiretinal membrane, and four with glaucoma. Sixty eyes had no other ophthalmic related pathologies (NOO), and had a mean pre-op CFT of 222 MUm, which progressively increased up to the 60th day post-op, reaching a mean of 227.2 MUm. No pseudophakic cystoid macular edema was observed. The mean CFT was statistically significantly different (p<0.001) between NOO and diabetic patients from 30 days post-op. Four eyes presented with preoperative diagnosis of AMD as measured by ophthalmoscopy. After completion of the OCT, which was performed within 5 h before surgery, six additional patients were found to have AMD. Of the 98 total eyes, 10 were diagnosed with maculopathy only by OCT exam. Binocular indirect ophthalmoscopy (BIO) was unable to detect such changes. CONCLUSION: OCT diagnosed preoperative maculopathies in 21.4% of the patients, and was more effective than BIO (11.2%). OCT showed a progressive increase in CFT in diabetics up to 180 days post-operatively, as well as greater CFT in male patients and patients older than 70 years. PMID- 26375339 TI - Evaluation of central and peripheral corneal thicknesses in patients with rheumatoid arthritis. AB - PURPOSE: To evaluate central corneal thickness (CCT) and peripheral corneal thickness (PCT) in patients with rheumatoid arthritis (RA) and to assess the relationships among the corneal parameters, dry eye disease, and clinical variables of RA. METHODS: A total of 58 RA patients and 58 control subjects participated in this study. A detailed ophthalmological examination was performed on each subject. Dry eye evaluation was performed using Schirmer's test, tear break-up time (TBUT), corneal fluorescein staining, and Ocular Surface Disease Index (OSDI). Corneal thickness at the apex point, the center of the pupil, the thinnest point, and PCT (3 mm from the apex to the superior, inferior, nasal, and temporal locations) were evaluated using Scheimpflug imaging (Pentacam(r)). Additionally, the relative peripheral index (RPI) was calculated by dividing the PCT by the CCT. The disease severity and quality of life were evaluated with DAS28 and HAQ, respectively. The laboratory evaluation comprised ESR and CRP. RESULTS: The mean corneal thicknesses at the apex point, the center of the pupil, the thinnest point, and the superior, inferior, nasal, and temporal points were significantly thinner in RA patients than controls. Schirmer's test scores and TBUT were significantly lower, and corneal staining and OSDI scores were significantly higher in RA patients. There were no significant correlations between the corneal parameters and the clinical variables of RA or dry eye tests. CONCLUSION: The CCT and PCT were thinner in RA patients compared to those in control subjects. However, there were no significant correlations between the corneal parameters and the clinical variables of RA or dry eye tests. PMID- 26375341 TI - Evaluation of MEWDS-like lesions with fluorescein angiography and its frequency at an ophthalmic emergency department in Rio de Janeiro. AB - PURPOSE: To characterize multiple evanescent white dot syndrome (MEWDS)-like lesions as diagnosed by clinical exam and fluorescein angiography (FA) to build an epidemiological profile of this disease and highlight the most common angiographical aspects. It is important to emphasize the existence of this syndrome and improve patients' information about the natural good course of this disease. METHODS: A cross-sectional study including all FA performed from July 2006 to October 2012 (6,111 exams analyzed) in patients at our ophthalmic emergency department, with analysis of the different angiographic aspects of the MEWDS-diagnosed cases. RESULTS: Among the 6,111 angiographies analyzed, 15 MEWDS cases were detected; the patients ranged in age from 13 to 42 years old, and the male/female ratio was 60% to 40% (nine male and six female). The most common FA aspects included hyperfluorescent dots, dots and spots in the retinal mid periphery, and foveal granularity in 46% of the cases. CONCLUSIONS: MEWDS has a good prognosis, with spontaneous involution, which makes it difficult to diagnose because of the delayed access to ophthalmological assistance, in special FA examination, which highlights the lesions. This study was possible due to the quick access facility at a private ophthalmic emergency department and examination by an experienced ophthalmologist, along with complementary diagnosis by FA and better perception of the patients, thus ensuring good prognosis. PMID- 26375342 TI - Localized flap melt after Nd-YAG laser treatment in recurrent post-LASIK epithelial ingrowth. AB - Neodymium: Yttrium-Aluminum-Garnet (Nd-YAG) laser treatment of epithelial ingrowth was found promising with high success rates in cases of primary post LASIK epithelial ingrowth. However, the application range of this procedure is not well-known. For the first time, the authors report the outcome of a patient treated with Nd-YAG laser for multiple recurrences of post-laser in situ keratomileusis epithelial ingrowth. PMID- 26375343 TI - Postoperative fungal endophthalmitis caused by Trichosporon asahii treated with voriconazole. AB - Postoperative fungal endophthalmitis is a rare but devastating complication of cataract surgery. Vitrectomy and intravitreal amphotericin B injection as well as administration of systemic antifungal agents have been suggested as optimal treatments for fungal endophthalmitis. However, this therapy may fail to eliminate fungal species resistant to current antifungal agents. The saprophytic fungus Trichosporon asahii is frequently observed as a cause of endogenous endophthalmitis in immunosuppressed patients. We report a case of postoperative endophthalmitis caused by T. asahii, resistant to amphotericin B. To the best of our knowledge, this is the first report of T. asahii endophthalmitis successfully treated with intravitreal and systemic voriconazole, pars plana vitrectomy, and removal of the intraocular lens and entire lens capsule. PMID- 26375344 TI - Corneal melanosis successfully treated using topical mitomycin-C and alcohol corneal epitheliectomy: a 3-year follow-up case report. AB - We report a case of primary acquired corneal melanosis without atypia associated with corneal haze in a patient with a history of limbal malignant melanoma and the effect of mitomycin-C. A 75-year-old woman with a history of limbal malignant melanoma presented with loss of vision in right eye. Corneal examination showed a patchy melanotic pigmentation with a central haze. Topical mitomycin-C improved visual acuity and corneal haze. However, the pigmented lesions persisted, and they were removed with alcohol corneal epitheliectomy. Histopathological examination demonstrated primary acquired melanosis without atypia. The lesions were successfully removed, and there were no recurrences during the follow-up period of 36 months. The association of conjunctival and corneal melanosis without atypia is a rare condition. In addition, co-existence of central corneal haze and melanosis may decrease visual acuity. Topical mitomycin-C and alcohol corneal epitheliectomy can be useful treatments in this condition. PMID- 26375345 TI - Drastic effect of ranibizumab on choroidal neovascularization in idiopathic angioid streaks. AB - A 28-year-old man presented with bilateral vision loss. His best-corrected visual acuity (BCVA) was 0.3 in the right eye (OD) and 0.6 in the left eye (OS). Fundoscopy and fluorescein angiography showed angioid streaks encircling the optic discs of both eyes (OU). Spectral Domain Optical Coherence Tomography (SD OCT) showed bilateral macular serous detachment. Systemic and ocular screening tests showed no specific cause for the angioid streaks. The patient had previously received pegaptanib sodium injection on three occasions, photodynamic therapy in OS, and no treatment in OD. Upon intravitreal injection of ranibizumab (twice in OU), subretinal fluid was nearly eliminated in OU. BCVA increased to 0.6 in OD and 0.9 in OS, and remained improved until 6 months after treatment. PMID- 26375346 TI - Anophthalmic socket: choice of orbital implants for reconstruction. AB - This literature review considers the treatment of an anophthalmic socket and the controversial aspects of the implants used to restore the lost volume after enucleation or evisceration, including the different materials employed and the main problems encountered during anophthalmic socket reconstruction. Since the 1980s, when integrated implants were proposed, there has been much controversy about what is the best implant for restoring the lost volume in an anophthalmic socket: integrated or non-integrated implants. Thus, we present this literature review to provide guidance to doctors and consumers. PMID- 26375347 TI - Author reply: approach to micronutrition in age-related macular degeneration. PMID- 26375348 TI - Combined 20- and 23-gauge pars plana vitrectomy. PMID- 26375349 TI - Acute opacification of hydrophobic acrylic intraocular lens during implantation: result of temperature variation. PMID- 26375350 TI - Cataract surgery teaching. PMID- 26375351 TI - Degowning the controversies of contact precautions for methicillin-resistant Staphylococcus aureus: A review. AB - BACKGROUND: Contact precautions (CPs) are recommended to prevent methicillin resistant Staphylococcus aureus (MRSA) transmission in institutions. Rising doubts about CP effectiveness and recognition of unintended consequences for patients have raised questions about the benefit. The objective of this study was to evaluate the effectiveness and adverse outcomes associated with CPs for prevention of MRSA transmission. METHODS: We searched PubMed, Embase, and the Cochrane Library for articles related to effectiveness and adverse outcomes of CPs in patients with MRSA. Criteria for inclusion included the following: articles conducted in the United States, articles performed in an acute care setting, articles that were not a case series or review, and those with standardized collection of data or inclusion of case and control groups. Results were summarized and examined for potential limitations. Recommendations were based on our findings. RESULTS: CPs reduced MRSA transmission in epidemic settings and in instances with high compliance, but a decrease in infection rates was not shown. Unintended consequences of CPs include decreased health care provider (HCP) time spent with patients, low HCP compliance, decreased perceptions of comfort from patients, and greater likelihood of patient complaints and negative psychologic implications. CONCLUSION: In endemic settings, there are few data to support routine use of CPs to control the spread of MRSA. Education should be performed in hospitals to improve patients' perception of care and understanding of CPs when implemented and HCPs' adherence to good hand hygiene and standard precautions practices. PMID- 26375352 TI - Design, synthesis and biological evaluation of tricyclic diterpene derivatives as novel neuroprotective agents against ischemic brain injury. AB - Lead compound 7 has neuroprotective effects, and it was discovered by screening a small synthetic natural product-like (NPL) library. Based on the lead, a series of tricyclic diterpene derivatives was designed and synthesized, and their neuroprotective effects were further evaluated against glutamate-, oxygen and glucose deprivation (OGD)- and nutrient deprivation-induced neuronal injury using cell-based assays. To our delight, most of these synthetic compounds exhibited increased neuroprotective effects and blood-brain barrier (BBB) permeability without cellular toxicity. The most potent compound, compound 30, showed significantly improved neuroprotection against neuronal injury in primary neurons. Furthermore, compound 30 exhibited remarkable neuroprotection in transient middle cerebral artery occlusion (tMCAO) rats by reducing their infarct sizes and neurological deficit scores. A mechanistic exploration using in vitro and in vivo experiments showed that the neuroprotection of these compounds was at least partly mediated by improving the levels of glutathione (GSH), superoxide dismutase (SOD) and heme oxygenase-1 (HO-1) protein. Therefore, these tricyclic diterpene derivatives could be used as promising leads for the development of a new type of neuroprotective agents against ischemic brain injury. PMID- 26375353 TI - Novel 3,4-methylenedioxyde-6-X-benzaldehyde-thiosemicarbazones: Synthesis and antileishmanial effects against Leishmania amazonensis. AB - A series of eleven 3,4-methylenedioxyde-6-X-benzaldehyde-thiosemicarbazones (16 27) was synthesised as part of a study to search for potential new drugs with a leishmanicidal effect. The thiosemicarbazones, ten of which are new compounds, were prepared in good yields (85-98%) by the reaction of 3,4-methylenedioxyde-6 benzaldehydes (6-X-piperonal), previously synthesised for this work by several methodologies, and thiosemicarbazide in ethanol with a few drops of H2SO4. These compounds were evaluated against Leishmania amazonensis promastigotes, and derivatives where X = I (22) and X = CN (23) moieties showed impressive results, having IC50 = 20.74 MUM and 16.40 MUM, respectively. The intracellular amastigotes assays showed IC50 = 22.00 MUM (22) and 17.00 MUM (23), and selectivity index >5.7 and >7.4, respectively, with a lower toxicity compared to pentamidine (positive control, SI = 4.5). The results obtained from the preliminary QSAR study indicated the hydrophobicity (log P) as a fundamental parameter for the 2D-QSAR linear model. A molecular docking study demonstrated that both compounds interact with flavin mononucleotide (FMN), important binding site of NO synthase. PMID- 26375354 TI - The functional biology of human milk oligosaccharides. AB - Human milk oligosaccharides (HMOs) are a group of complex sugars that are highly abundant in human milk, but currently not present in infant formula. More than a hundred different HMOs have been identified so far. The amount and composition of HMOs are highly variable between women, and each structurally defined HMO might have a distinct functionality. HMOs are not digested by the infant and serve as metabolic substrates for select microbes, contributing to shape the infant gut microbiome. HMOs act as soluble decoy receptors that block the attachment of viral, bacterial or protozoan parasite pathogens to epithelial cell surface sugars, which may help prevent infectious diseases in the gut and also the respiratory and urinary tracts. HMOs are also antimicrobials that act as bacteriostatic or bacteriocidal agents. In addition, HMOs alter host epithelial and immune cell responses with potential benefits for the neonate. The article reviews current knowledge as well as future challenges and opportunities related to the functional biology of HMOs. PMID- 26375355 TI - Human breast milk: A review on its composition and bioactivity. AB - Breast milk is the perfect nutrition for infants, a result of millions of years of evolution, finely attuning it to the requirements of the infant. Breast milk contains many complex proteins, lipids and carbohydrates, the concentrations of which alter dramatically over a single feed, as well as over lactation, to reflect the infant's needs. In addition to providing a source of nutrition for infants, breast milk contains a myriad of biologically active components. These molecules possess diverse roles, both guiding the development of the infants immune system and intestinal microbiota. Orchestrating the development of the microbiota are the human milk oligosaccharides, the synthesis of which are determined by the maternal genotype. In this review, we discuss the composition of breast milk and the factors that affect it during the course of breast feeding. Understanding the components of breast milk and their functions will allow for the improvement of clinical practices, infant feeding and our understanding of immune responses to infection and vaccination in infants. PMID- 26375356 TI - Structure of a randomly grown 2-d network. AB - We introduce a growing random network on a plane as a model of a growing neuronal network. The properties of the structure of the induced graph are derived. We compare our results with available data. In particular, it is shown that depending on the parameters of the model the system undergoes in time different phases of the structure. We conclude with a possible explanation of some empirical data on the connections between neurons. PMID- 26375357 TI - Bias modification training can alter approach bias and chocolate consumption. AB - Recent evidence has demonstrated that bias modification training has potential to reduce cognitive biases for attractive targets and affect health behaviours. The present study investigated whether cognitive bias modification training could be applied to reduce approach bias for chocolate and affect subsequent chocolate consumption. A sample of 120 women (18-27 years) were randomly assigned to an approach-chocolate condition or avoid-chocolate condition, in which they were trained to approach or avoid pictorial chocolate stimuli, respectively. Training had the predicted effect on approach bias, such that participants trained to approach chocolate demonstrated an increased approach bias to chocolate stimuli whereas participants trained to avoid such stimuli showed a reduced bias. Further, participants trained to avoid chocolate ate significantly less of a chocolate muffin in a subsequent taste test than participants trained to approach chocolate. Theoretically, results provide support for the dual process model's conceptualisation of consumption as being driven by implicit processes such as approach bias. In practice, approach bias modification may be a useful component of interventions designed to curb the consumption of unhealthy foods. PMID- 26375358 TI - Derailing the streetcar named desire. Cognitive distractions reduce individual differences in cravings and unhealthy snacking in response to palatable food. AB - People who are sensitive to food temptations are prone to weight gain and obesity in food-rich environments. Understanding the factors that drive their desire to eat is key to limiting their reactions to available food. This study tested whether individual differences in sensitivity to hedonic food cues are cognitively based and, accordingly, can be regulated by blocking cognitive resources. To this end, one lab study (Study 1; N = 91) and one field study (Study 2; N = 63) measured sensitivity to hedonic food cues using the Power of Food Scale (PFS; Lowe et al., 2009) and assessed participants' appetitive responses to high-calorie food options. To test the role of cognitive elaboration of food cues, participants completed a menu-selection task to induce food cravings and then were free to elaborate those cravings (control group) or were blocked from doing so by cognitive distraction (playing Tetris, solving puzzles; experimental group). Compared to non-sensitive participants, sensitive participants displayed a greater attentional bias to high-calorie food (Study 1), reported stronger cravings (Study 2), and more often chose an unhealthy snack (Studies 1 & 2), but only when they had not been distracted. When distracted, all participants were similarly unresponsive to high-calorie food. This finding suggests that temptation can be effectively controlled by blocking people's cognitive resources, even for people highly sensitive to hedonic food cues. PMID- 26375359 TI - A longitudinal study on emotional dysregulation and obesity risk: From pregnancy to 3 years of age of the baby. AB - Some recent findings indicate that maternal sensitivity and emotional regulation may play a key role in predicting the risk for obesity of the child in early ages. The current article describes a longitudinal study encompassing more than 50 women, across a time-span that currently goes from pregnancy (n = 65) to three years of age of the baby (n = 53). In a previous report on our ongoing research project, we showed that emotional regulation during pregnancy and pre-pregnancy BMI significantly predicted the quality of the early, dyadic feeding interactions, at 7 months of age of the baby. The current study confirmed and extended those findings, by showing that maternal emotional dysregulation (r = .355, p = .009) and pre-pregnancy BMI (r = .389, p = .004) predicted the BMI of the child at three years of age too, with a medium to large effect size. However, neither maternal emotional regulation nor pre-pregnancy BMI significantly predicted infant attachment at one year of age. PMID- 26375360 TI - Copeptin improves the sensitivity of cardiac troponin in patients 70 years or older, but not enough to rule out myocardial infarction at emergency department presentation. AB - OBJECTIVES: We aimed to evaluate the diagnostic performance of the combination of cardiac troponin (cTn) and copeptin in a population older than 70 years of age to rule out non-ST-elevation myocardial infarction (NSTEMI) at emergency department (ED) presentation. METHODS: Among 885 analyzed patients with acute chest pain presenting to the ED, 218 (25%) were aged at least 70 years. RESULTS: Patients with elevated copeptin values at presentation were more often aged at least 70 years and had higher blood pressure. Patients at least 70 years without NSTEMI more frequently had elevated copeptin values than younger counterparts (42 vs. 25%, P<0.0001). Bootstrap analysis for the diagnosis of NSTEMI indicated an optimal copeptin threshold value at 8.1 pmol/l in patients less than 70 years and at 10.7 pmol/l in patients at least 70 years. In patients at least 70 years, the combination of copeptin with cTnI significantly improved the sensitivity for the diagnosis of NSTEMI, at all copeptin thresholds tested, but the negative predictive value remained below 95%. CONCLUSION: The combination of copeptin with conventional cTnI significantly improved sensitivity for the diagnosis of NSTEMI in patients at least 70 years. However, this improvement was not enough to rule out NSTEMI with a single draw strategy at ED presentation. PMID- 26375361 TI - The diagnostic accuracy of the HITSNS prehospital triage rule for identifying patients with significant traumatic brain injury: a cohort study. AB - Diversion of suspected traumatic brain injury (TBI) patients to trauma centres may improve outcomes by expediting access to specialist neurosurgical care. This study aimed to determine the accuracy of the Head Injury Straight to Neurosurgery (HITSNS) triage rule for identifying patients with significant TBI. A diagnostic cohort study was performed using data from the HITSNS trial, the Trauma Audit and Research Network registry and the North East Ambulance service database. Sensitivity and specificity of the HITSNS triage rule were calculated against a reference standard of significant TBI, defined by a cranial Abbreviated Injury Scale score of at least 3 or by the performance of a neurosurgical procedure. A total of 3628 patients were included in the complete case analyses. The HITSNS triage tool demonstrated a sensitivity of 28.3% (95% confidence interval 21.8 35.4) and a specificity of 94.4% (95% confidence interval 93.6-95.2). The low sensitivity of the HITSNS triage rule suggests that a considerable proportion of patients with significant TBI may not be triaged directly to trauma centres, and further research is needed to improve the accuracy of bypass protocols. PMID- 26375362 TI - A discussion concerning direct bone regeneration on and around inserted dental implants in maxillary sinus lifting procedures without any placement of bony substitutes. PMID- 26375363 TI - Dental implant placement after maxillary sinus lift without a graft: a feasible option. PMID- 26375365 TI - Rapid and simple detection of gero-suppressive agents. PMID- 26375364 TI - Expression of Inflammatory and Regenerative Genes in a Model of Liver Ischemia/Reperfusion and Partial Hepatectomy. AB - PURPOSE/AIM: Hepatic ischemia/reperfusion (I/R) describes the paradox of additional tissue injury caused by reperfusion. The aim of this survey was to investigate the mRNA expression of genes exerting their inflammatory and regenerative reaction in a porcine model of I/R and extended hepatectomy. MATERIAL AND METHODS: Twelve pigs were used, weighing 30-35 kg in average, which were allocated in two groups: the I/R group with eight pigs and the sham-operated (control) one with four pigs. The I/R group underwent portacaval anastomosis and Pringle maneuver followed by extended hepatectomy. The hepatoduodenal ligament was occluded for 150 min and the liver remnant was reperfused for 24 hours. Blood samples were steadily received throughout the surgical procedure, where hepatic biopsies were taken for pathological evaluation. Animals were sacrificed in 24 hours after the onset of reperfusion. RESULTS: Between the two groups, statistically significant differences were noticed in serum values of AST, ALT, ALP, and total bilirubin in the early and late phase of reperfusion. The mRNA expression of iNOS, IL-1b, and TGF-a did not increase significantly in the I/R group. Conversely, the mRNA modification of IL-6, STAT-3, and E-selectin demonstrated significantly increased expression in I/R animals. CONCLUSIONS: In the present survey, a new I/R swine model was proposed and specific parameters were analyzed, revealing differences between the study groups. PMID- 26375366 TI - Dual mTORC1/C2 inhibitors: gerosuppressors with potential anti-aging effect. AB - Over the past decade, our understanding of the molecular and cellular mechanisms presiding over cellular and tissue decline with aging has greatly advanced. Classical hallmarks of aging cell include increasing levels of reactive oxygen species, DNA damage and senescence entry, which disrupt tissue architecture and function. Tissue dysfunction with aging has been shown to correlate with a cellular switch from a G0 reversible quiescence state into a G0 irreversible senescence state (geroconversion), causing a permanent proliferative block. The TOR (target of rapamycin) kinase has been shown to promote geroconversion. Rapamycin and other rapalogs specifically suppress activity of the mammalian TOR (mTOR) complex 1 (mTORC1) -but not mTOR complex 2 (mTORC2)- and decrease senescence entry, thus preserving proliferative potential. In this perspective, we briefly comment recent progress of Leontieva and colleagues showing a new class of non-rapalog drugs that target simultaneously mTORC1 and mTORC2 and prevent geroconversion in a more efficient way than rapamycin. Its potential future use as rejuvenating, anti-aging therapeutics is therefore proposed. PMID- 26375367 TI - A Prediction Rule for Risk Stratification of Incidentally Discovered Gallstones: Results From a Large Cohort Study. AB - BACKGROUND & AIMS: No one knows exactly what proportion of gallstones cause clinical events among subjects unaware of their gallstone status. We investigated the long-term occurrence of clinical events of gallstones and associations between ultrasound observations and clinical events. METHODS: We analyzed data from 3 randomly selected groups in the general population of urban Copenhagen (age, 30-70 y) participating in an international study of cardiovascular risk factors (the Multinational mONItoring of trends and determinants in CArdiovascular disease study). In this study, participants (n = 6037) were examined from 1982 through 1994, and underwent abdominal ultrasound examinations to detect gallstones. Our study population comprised 664 subjects with gallstones; subjects were not informed of their gallstone status. Participants were followed up for clinical events through central registers until December 31, 2011. Independent variables included ultrasound characteristics, age, sex, comorbidity, and female-associated factors, which were analyzed using Cox regression. RESULTS: Study participants were followed up for a median of 17.4 years (range, 0.1-29.1 y); 99.7% of participants completed the study. A total of 19.6% participants developed events (8.0% complicated and 11.6% uncomplicated). Ten percent had awareness of their gallstones; awareness was associated with uncomplicated and complicated events. Stones larger than 10 mm were associated with all events (hazard ratio [HR], 2.31; 95% confidence interval [CI], 1.45 3.69), acute cholecystitis (HR, 9.49; 95% CI, 2.05-43.92), and uncomplicated events (HR, 2.55; 95% CI, 1.38-4.71), including cholecystectomy (HR, 2.69; 95% CI, 1.29-5.60). Multiple stones were associated with all events (HR, 1.68; 95% CI, 1.00-2.81), complicated events (HR, 2.52; 95% CI, 1.05-6.04), and common bile duct stones (HR, 11.83; 95% CI, 1.54-91). There was an association between gallstones more than 5 years old and acute cholecystitis. Female sex was associated with all and uncomplicated events. We found a negative association between participant age and all events, uncomplicated events, and acute cholecystitis. Comorbidities and female-associated factors (intake of birth control pills or estrogens and number of births) were not associated with events. Compared with men with a single stone of 10 mm or smaller (reference), women with multiple stones greater than 10 mm had the highest risk for events (HR, 11.05; 95% CI, 3.76-32.44; unadjusted absolute risk, 0.0235 events/person-years). CONCLUSIONS: Fewer than 20% of subjects with gallstones develop clinical events. Larger, multiple, and older gallstones are associated with events. Further studies are needed to confirm the prediction rules. PMID- 26375368 TI - "Tent-Pole" for Reconstruction of Large Alveolar Defects: A Case Report. AB - Severe tridimensional alveolar ridge defects complicate the placement of dental implants, and surgical removal of some oral tumors might not leave adequate bone for dental implant placement. Regenerating an adequate amount of bone vertically and horizontally to achieve a satisfying outcome for well-osseointegrated implants and thus ensure long-term success of implant restoration is challenging. This report describes the clinical feasibility of a simple approach using a screw tent-pole combined with guided bone regeneration to augment complicated tridimensional alveolar ridge defects in a case of extensive bone loss due to maxillary tumor surgery. Titanium screws were arranged in "tented" fashion to provide stable room for bone regeneration. Regenerated bone was achieved and 2 more implants were placed in the regenerated ridge 10 months later, leading to a successful maxillary prosthesis. PMID- 26375369 TI - Inferring pathological states in cortical neuron microcircuits. AB - The brain activity is to a large extent determined by states of neural cortex microcircuits. Unfortunately, accuracy of results from neural circuits' mathematical models is often biased by the presence of uncertainties in underlying experimental data. Moreover, due to problems with uncertainties identification in a multidimensional parameters space, it is almost impossible to classify states of the neural cortex, which correspond to a particular set of the parameters. Here, we develop a complete methodology for determining uncertainties and the novel protocol for classifying all states in any neuroinformatic model. Further, we test this protocol on the mathematical, nonlinear model of such a microcircuit developed by Giugliano et al. (2008) and applied in the experimental data analysis of Huntington's disease. Up to now, the link between parameter domains in the mathematical model of Huntington's disease and the pathological states in cortical microcircuits has remained unclear. In this paper we precisely identify all the uncertainties, the most crucial input parameters and domains that drive the system into an unhealthy state. The scheme proposed here is general and can be easily applied to other mathematical models of biological phenomena. PMID- 26375370 TI - Dissecting the dynamics of epigenetic changes in phenotype-structured populations exposed to fluctuating environments. AB - An enduring puzzle in evolutionary biology is to understand how individuals and populations adapt to fluctuating environments. Here we present an integro differential model of adaptive dynamics in a phenotype-structured population whose fitness landscape evolves in time due to periodic environmental oscillations. The analytical tractability of our model allows for a systematic investigation of the relative contributions of heritable variations in gene expression, environmental changes and natural selection as drivers of phenotypic adaptation. We show that environmental fluctuations can induce the population to enter an unstable and fluctuation-driven epigenetic state. We demonstrate that this can trigger the emergence of oscillations in the size of the population, and we establish a full characterisation of such oscillations. Moreover, the results of our analyses provide a formal basis for the claim that higher rates of epimutations can bring about higher levels of intrapopulation heterogeneity, whilst intense selection pressures can deplete variation in the phenotypic pool of asexual populations. Finally, our work illustrates how the dynamics of the population size is led by a strong synergism between the rate of phenotypic variation and the frequency of environmental oscillations, and identifies possible ecological conditions that promote the maximisation of the population size in fluctuating environments. PMID- 26375371 TI - The tradeoff between signal detection and recognition rules auditory sensitivity under variable background noise conditions. AB - Animal acoustic communication commonly takes place under masked conditions. For instance, sound signals relevant for mating and survival are very often masked by background noise, which makes their detection and recognition by organisms difficult. Ambient noise (AN) varies in level and shape among different habitats, but also remarkable variations in time and space occurs within the same habitat. Variable AN conditions mask hearing thresholds of the receiver in complex and unpredictable ways, thereby causing distortions in sound perception. When communication takes place in a noisy environment, a highly sensitive system might confer no advantage to the receiver compared to a less sensitive one. The effects of noise masking on auditory thresholds and hearing-related functions are well known, and the potential role of AN in the evolution of the species' auditory sensitivity has been recognized by few authors. The mechanism of the underlying selection process has never been explored, however. Here I present a simple fitness model that seeks for the best sensitivity of a hearing system performing the detection and recognition of the sound under variable AN conditions. The model predicts higher sensitivity (i.e. lower hearing thresholds) as best strategy for species living in quiet habitats and lower sensitivity (i.e. higher hearing thresholds) as best strategy for those living in noisy habitats provided the cost of incorrect recognition is not low. The tradeoff between detection and recognition of acoustic signals appears to be a key factor determining the best level of hearing sensitivity of a species when acoustic communication is corrupted by noise. PMID- 26375372 TI - The independent impact of newborn hepatitis B vaccination on reducing HBV prevalence in China, 1992-2006: A mathematical model analysis. AB - OBJECTIVE: To evaluate the independent impact of newborn hepatitis B vaccination on reducing HBV prevalence in China, from its introduction in 1992 to 2006. METHODS: An age- and time-dependent discrete dynamic model was developed to simulate HBV transmission in China under the assumptions of no any change in interventions and only with newborn vaccination introduction, respectively. The initial conditions of the model were determined according to the national serosurvey in 1992. The simulated results were compared with the observed results of the national serosurvey in 2006, and the contribution rate of newborn vaccination on reducing HBV prevalence was calculated overall and by birth cohort. RESULTS: The total HBV prevalence would remain stable through the 14-year period if no any change in interventions, but decrease year by year if only with newborn vaccination introduction. Newborn vaccination could account for more than 50% of the reduction of the total HBV prevalence, although the full 3-dose and timely birth dose vaccination coverage rates were low in the early years. The results by birth cohort showed that the higher the two coverage rates, the higher contribution rate on reducing HBV prevalence. For the 2005 birth cohort which had high levels in the two coverage rates, the contribution rate could reach more than 95%. CONCLUSION: Newborn hepatitis B vaccination from 1992 to 2006 in China had played the most important role in reducing HBV prevalence. Newborn vaccination with high full 3-dose and timely birth dose coverage rates is the decisive factor in controlling hepatitis B in China. PMID- 26375373 TI - Contraversive Ocular Tilt Reaction in Pontomedullary Infarction. PMID- 26375374 TI - Varicella Zoster Virus Cerebellitis Without a Rash in an Immunocompetent 85-Year Old Patient. AB - BACKGROUND: Reactivation of the varicella zoster virus (VZV) in adults rarely presents with neurological symptoms without a rash. To our knowledge, so far, only 3 additional cases of VZV cerebellitis, which presented without a rash and were proven by cerebrospinal fluid analysis, have been reported in the literature. CASE REPORT: An immunocompetent 85-year-old patient presented with a new-onset tremor. He had no rash, had a normal brain computed tomography and magnetic resonance imaging, and had minimal cerebrospinal fluid findings. Eventually, he was diagnosed as having varicella zoster virus cerebellitis only on the basis of a virological examination. CONCLUSIONS: The manifestation of a new-onset tremor and gait ataxia should raise a suspicion of cerebellitis caused by VZV, even in the absence of cutaneous manifestations or typical imaging findings. PMID- 26375375 TI - A Myocardial Infarction During Intravenous Recombinant Tissue Plasminogen Activator Infusion for Evolving Ischemic Stroke. AB - INTRODUCTION: There are reports of an ischemic stroke during intravenous recombinant tissue-type plasminogen activator (rtPA) for evolving myocardial infarction (MI), and the risk of stroke shortly after an acute MI seems to be higher than in the control population, attributed to intracardiac thrombus formation. CASE REPORT: We report a case of fatal MI developing immediately after the start of rtPA infusion for middle cerebral artery stroke in an 88-year-old woman. We assume that the systemic thrombolysis with rtPA led to the fragmentation of an underlying cardiac thrombus, which embolized and occluded the coronary artery and caused MI. This hypothesis is discussed with respect to a short review of the related literature. CONCLUSIONS: An embolic MI seems to be a rare but serious complication in thrombolysis therapy with rtPA. PMID- 26375376 TI - Successful Systemic Thrombolysis in an Adolescent With Acute Ischemic Stroke. AB - INTRODUCTION: Current treatment guidelines for acute ischemic stroke do not recommend thrombolytic therapy in children and adolescents as data are still very scarce. CASE REPORT: We report the case of a 15-year-old boy who suddenly developed severe left-sided weakness and speech difficulty while stooling. Upon arrival at our Emergency Department, the National Institute of Health Stroke Scale (NIHSS) score was 18. Urgent neurovascular ultrasound showed a distal occlusion of the right internal carotid artery and occlusion at the origin of the middle cerebral artery (MCA) and the anterior cerebral artery. He was treated 2 hours after symptom onset with intravenous recombinant tissue plasminogen activator without any complication. At the end of thrombolysis, a complete recanalization was shown by transcranial Doppler sonography, although a brain magnetic resonance imaging disclosed an acute right middle cerebral artery stroke. At discharge, the boy had mild weakness on his left leg and slight left facial palsy: the NIHSS score was 2. To our knowledge, this is the first intravenous thrombolytic treatment ever reported in an adolescent in Italy. CONCLUSIONS: Despite the lack of evidence regarding the safety and the efficacy of recombinant tissue plasminogen activator in pediatric stroke, this treatment option should be considered, especially in adolescents presenting within 3 hours from symptom onset in centers with consolidated experience in adult thrombolysis. PMID- 26375377 TI - Friedreich Ataxia: From the Eye of a Molecular Biologist. AB - Friedreich ataxia (FRDA) is caused by the expansion of a GAA triplet repeat in the first intron of the FXN gene. This disease was named after Nicholaus Friedreich, Germany, who depicted the essential finding. Among ataxias, FRDA is the most common hereditary ataxia. It has the autosomal recessive pattern of inheritance. The expansion of the GAA triplet repeat hinders the transcription, thereby reducing the level of the FXN transcript and consequently reducing the level of frataxin, a 210-amino acid protein. The disease pathogenesis is fundamentally due to a lack of frataxin, which is claimed to play a role in iron sulfur cluster synthesis. Oxidative stress builds up as a result of Fe accumulation in the mitochondria, causing degeneration of the cells, which primarily occurs in the neurons and later in the cardiac tissues, and to some extent in the pancreas. The therapeutic interventions are at infancy; however, current treatments are targeted toward the reduction of iron overload and its effects. PMID- 26375378 TI - Palladium-Catalyzed Double-Decarboxylative Addition to Pyrones: Synthesis of Conjugated Dienoic Esters. AB - An interceptive decarboxylative allylation protocol has been developed utilizing pyrone as a C4 synthon. This palladium-catalyzed transformation difunctionalizes the pyrone moiety by in situ generation and activation of both the electrophile and nucleophile via a double decarboxylation pathway. Ultimately, allyl carbonates react smoothly with 2-carboxypyrone under mild reaction conditions to generate synthetically useful acyclic dienoic esters, forming carbon dioxide as the sole byproduct. PMID- 26375379 TI - Variation in Physician Office Visit Rates by Patient Characteristics and State, 2012. AB - In 2012, 74% of children and adults with a usual place to visit listed a doctor's office as their usual place for care (1,2). This report examines the rate of physician office visits by patient age, sex, and state. Visits by adults with private insurance as their expected source of payment were also examined. Estimates are based on the 2012 National Ambulatory Medical Care Survey (NAMCS), a nationally representative survey of physician office visits. State estimates for the 34 most populous states are available for the first time. State refers to the location of the physician office visit. PMID- 26375380 TI - Abnormal frontal theta oscillations underlie the cognitive flexibility deficits in children with high-functioning autism spectrum disorders. AB - OBJECTIVE: Deficits in cognitive flexibility have been suggested to underlie the repetitive and stereotyped behavior in individuals with autism spectrum disorders (ASD). Because cognitive flexibility is primarily mediated by the frontal lobe, where structural and functional abnormalities have been extensively found in these individuals, it is conceivable that their deficits in cognitive flexibility are related to abnormal activations of the frontal lobe. The present study investigates cognitive flexibility and its underlying neurophysiological activities as indicated by theta oscillations in children with ASD. METHOD: Twenty-five children with high-functioning ASD and 25 IQ- and age-matched typically developing (TD) children were subjected to neuropsychological assessments on cognitive flexibility and electroencephalography recordings. RESULTS: The children with ASD performed significantly worse than the TD children across the tasks of cognitive flexibility, including the modified Wisconsin Card Sorting Test (WCST). These children also demonstrated a reduced increase of the theta power localized in multiple brain regions, including various sectors of the frontal lobe at the late stage (i.e., 600 ms-900 ms poststimulus interval) but not the early stage (i.e., 250 ms-550 ms poststimulus interval) of the performance of the modified WCST. The suppressed late frontal theta activities were further shown to be significantly correlated with a poorer performance on the cognitive flexibility measures. CONCLUSION: Our findings suggest that abnormal activations of multiple cortical regions, especially the frontal lobe, form the neural basis of the cognitive flexibility deficits in children with ASD. In addition, we found an EEG marker of cognitive flexibility which could be used to monitor treatment outcomes objectively. PMID- 26375381 TI - Solvent-free synthesis of crystalline metal phosphate oxalates with a (4,6) connected fsh topology. AB - Two new organically templated manganese phosphate oxalates were synthesized under solvent-free conditions. They have different three-dimensional structures with a (4,6)-connected fsh topology. It is interesting that the amine molecules can reverse the structure-building roles of the metal phosphate skeleton and metal oxalate substructure for formation of their fsh-type frameworks. PMID- 26375382 TI - Reaction of Human Cd7metallothionein and N-Ethylmaleimide: Kinetic and Structural Insights from Electrospray Ionization Mass Spectrometry. AB - The reaction of cadmium-binding human metallothionein-2A (Cd7MT) and N ethylmaleimide (NEM) is investigated by electrospray ionization-ion mobility-mass spectrometry (ESI IM-MS). MS provides a direct measure of the distribution of the kinetic intermediates as the reaction proceeds and provides new insights into the relative kinetic stability of the individual metal-thiolate bonds in Cd7MT. The rate constants for the various metal-retaining intermediates (Cd(i), intermediate with i Cd2+ ions attached) differ by >3 orders of magnitude: Cd4< Cd3< Cd2< Cd1~ Cd6 < Cd7 < Cd5. The reaction is viewed as a two-component cooperative process, rapid loss of three Cd2+ ions followed by slow loss of the remaining four Cd2+ ions, and Cd4NEM10MT was observed as the least reactive intermediate during the entire displacement process. "MS-CID-IM-MS", a top-down approach that provides two-dimensional dispersion (size to charge by IM; mass to charge by MS) of the CID fragment ions, was used for direct analysis of the kinetic intermediate [Cd4NEM10MT]5+ ion. The results provide direct evidence that the four Cd2+ ions located in the alpha-domain are retained, indicative of the greater kinetic stability for the alpha-domain. Further, the mapping of the alkylation sites in the [Cd4NEM10MT]5+ ion reveals that not only the nine cysteines in the beta domain but Cys33 in the alpha-domain is selectively labeled. The kinetic lability of the Cd-Cys33 bond is unexpected. The structural and functional implications of these findings are discussed. PMID- 26375384 TI - Supramolecular Organization and siRNA Binding of Hyaluronic Acid-Coated Lipoplexes for Targeted Delivery to the CD44 Receptor. AB - The dynamics of the formation of siRNA-lipoplexes coated with hyaluronic acid (HA) and the parameters influencing their supramolecular organization were studied. The insertion of a HA-dioleylphosphatidylethanolamine (DOPE) conjugate in the liposome structure as well as subsequent complexation with siRNA increased the liposome size. Lipoplexes were around 110 nm at high +/- charge ratios with a zeta potential around +50 mV and around 230 nm at low +/- ratios, with a zeta potential that decreased to negative values, reaching -45 mV. The addition of the conjugate did not compromise siRNA binding to liposomes, although these nucleic acids induced a displacement of part of the HA-DOPE conjugate upon lipoplex formation, as confirmed by capillary electrophoresis. Isothermal titration calorimetry, X-ray diffraction studies, and cryo-TEM microscopy demonstrated that in addition to electrostatic interactions with siRNA a rearrangement of the lipid bilayers takes place, resulting in condensed oligolamellar vesicles. This phenomenon is dependent on the number of siRNA molecules and the degree of modification with HA. Finally, the suitable positioning of HA on the lipoplex surface and its ability to bind specifically to the CD44 receptors in a concentration-dependent manner was demonstrated by surface plasmon resonance analysis. PMID- 26375385 TI - Longevity and Education: A Demographic Perspective. AB - In the second half of the 20th century, the advances in human longevity observed have been accompanied by an increase in the disparities between countries and regions. Education is one of the strongest predictors of life expectancy. Studies have shown that both relative and absolute mortality differences by education within countries have been increasing, even in the most developed and egalitarian countries. It is possible to assume that groups of highly educated people who systematically display life expectancy levels which are higher than the observed best practice (record) life expectancy at the national level are vanguards who are leading the way toward a lengthening of life for the remaining population groups. This evidence based on population-level statistics and exploring an important single factor could inspire further discussion about the possibilities for extending human length of life at the national level. However, more comprehensive and reliable data covering a larger number of countries and more covariates are needed for understanding health effects of education and prospects of human longevity. PMID- 26375386 TI - Improved Icephobic Properties on Surfaces with a Hydrophilic Lubricating Liquid. AB - Slippery liquid-infused porous surfaces were developed recently for icephobic surface applications. Perfluorinated liquids, silicone oil, hydrocarbon, and water were used as lubricating liquids to form a continuous layer on a suitable substrate to prevent icing. However, ice accretion performances of these surfaces have not been reported previously depending on the type of the lubricant. In this work, fluorinated aliphatics, polyalphaolefin, silicone oil, and decamethylcyclopenta siloxane were used as hydrophobic lubricants; water, ethylene glycol, formamide, and water-glycerine mixture were used as hydrophilic lubricants to be impregnated by hydrophobic polypropylene and hydrophilic cellulose-based filter paper surfaces; ice accretion, drop freezing delay time, and ice adhesion strength properties of these surfaces were examined; and the results were compared to those of the reference surfaces such as aluminum, copper, polypropylene, and polytetrafluoroethylene. An ice accretion test method was also developed to investigate the increase of the mass of formed ice gravimetrically by spraying supercooled water onto these surfaces at different subzero temperatures ranging between -1 and -5 degrees C. It was determined that hydrophilic solvents (especially a water-glycerine mixture) that impregnated hydrophilic porous surfaces would be a promising candidate for anti-icing applications at -2 degrees C and 56-83% relative humidity because ice accretion and ice adhesion strength properties of these surface decreased simultaneously in these conditions. PMID- 26375387 TI - A Systematic Review of Dropout From Psychotherapy for Posttraumatic Stress Disorder Among Iraq and Afghanistan Combat Veterans. AB - A significant number of veterans of the conflicts in Iraq and Afghanistan have posttraumatic stress disorder (PTSD), yet underutilization of mental health treatment remains a significant problem. The purpose of this review was to summarize rates of dropout from outpatient, psychosocial PTSD interventions provided to U.S. Operation Iraqi Freedom (OIF), Operation Enduring Freedom (OEF), and Operation New Dawn (OND) veterans with combat-related PTSD. There were 788 articles that were identified which yielded 20 studies involving 1,191 individuals eligible for the review. The dropout rates in individual studies ranged from 5.0% to 78.2%, and the overall pooled dropout rate was 36%, 95% CI [26.20, 43.90]. The dropout rate differed marginally by study type (routine clinical care settings had higher dropout rates than clinical trials) and treatment format (group treatment had higher dropout rates than individual treatment), but not by whether comorbid substance dependence was excluded, by treatment modality (telemedicine vs. in-person treatment), or treatment type (exposure therapy vs. nonexposure therapy). Dropout is a critical aspect of the problem of underutilization of care among OEF/OIF/OND veterans with combat related PTSD. Innovative strategies to enhance treatment retention are needed. PMID- 26375388 TI - Biochemical Characterization and Validation of a Catalytic Site of a Highly Thermostable Ts2631 Endolysin from the Thermus scotoductus Phage vB_Tsc2631. AB - Phage vB_Tsc2631 infects the extremophilic bacterium Thermus scotoductus MAT2631 and uses the Ts2631 endolysin for the release of its progeny. The Ts2631 endolysin is the first endolysin from thermophilic bacteriophage with an experimentally validated catalytic site. In silico analysis and computational modelling of the Ts2631 endolysin structure revealed a conserved Zn2+ binding site (His30, Tyr58, His131 and Cys139) similar to Zn2+ binding site of eukaryotic peptidoglycan recognition proteins (PGRPs). We have shown that the Ts2631 endolysin lytic activity is dependent on divalent metal ions (Zn2+ and Ca2+). The Ts2631 endolysin substitution variants H30N, Y58F, H131N and C139S dramatically lost their antimicrobial activity, providing evidence for the role of the aforementioned residues in the lytic activity of the enzyme. The enzyme has proven to be not only thermoresistant, retaining 64.8% of its initial activity after 2 h at 95 degrees C, but also highly thermodynamically stable (Tm = 99.82 degrees C, DeltaHcal = 4.58 * 10(4) cal mol(-1)). Substitutions of histidine residues (H30N and H131N) and a cysteine residue (C139S) resulted in variants aggregating at temperatures >=75 degrees C, indicating a significant role of these residues in enzyme thermostability. The substrate spectrum of the Ts2631 endolysin included extremophiles of the genus Thermus but also Gram-negative mesophiles, such as Escherichia coli, Salmonella panama, Pseudomonas fluorescens and Serratia marcescens. The broad substrate spectrum and high thermostability of this endolysin makes it a good candidate for use as an antimicrobial agent to combat Gram-negative pathogens. PMID- 26375389 TI - Metastatic Cutaneous Apocrine Adenocarcinoma Treated With a Combination of Pertuzumab-Based Targeted Therapy and Taxane Chemotherapy: A Case Report. PMID- 26375391 TI - Farmers' Intentions to Implement Foot and Mouth Disease Control Measures in Ethiopia. AB - The objectives of this study were to explore farmers' intentions to implement foot and mouth disease (FMD) control in Ethiopia, and to identify perceptions about the disease and its control measures that influence these intentions using the Health Belief Model (HBM) framework. Data were collected using questionnaires from 293 farmers in three different production systems. The influence of perceptions on the intentions to implement control measures were analyzed using binary logistic regression. The effect of socio-demographic and husbandry variables on perceptions that were found to significantly influence the intentions were analyzed using ordinal logistic regression. Almost all farmers (99%) intended to implement FMD vaccination free of charge. The majority of farmers in the pastoral (94%) and market oriented (92%) systems also had the intention to implement vaccination with charge but only 42% of the crop-livestock mixed farmers had the intention to do so. Only 2% of pastoral and 18% of crop livestock mixed farmers had the intention to implement herd isolation and animal movement restriction continuously. These proportions increased to 11% for pastoral and 50% for crop-livestock mixed farmers when the measure is applied only during an outbreak. The majority of farmers in the market oriented system (>80%) had the intention to implement herd isolation and animal movement restriction measure, both continuously and during an outbreak. Among the HBM perception constructs, perceived barrier was found to be the only significant predictor of the intention to implement vaccination. Perceived susceptibility, perceived benefit and perceived barrier were the significant predictors of the intention for herd isolation and animal movement restriction measure. In turn, the predicting perceived barrier on vaccination control varied significantly with the production system and the age of farmers. The significant HBM perception predictors on herd isolation and animal movement restriction control were significantly influenced only by the type of production system. The results of this study indicate that farmers' intentions to apply FMD control measures are variable among production systems, an insight which is relevant in the development of future control programs. Promotion programs aimed at increasing farmers' motivation to participate in FMD control by charged vaccination or animal movement restriction should give attention to the perceived barriers influencing the intentions to apply these measures. PMID- 26375392 TI - Correction: Lower Vocal Tract Morphologic Adjustments Are Relevant for Voice Timbre in Singing. PMID- 26375390 TI - DNA Damage Response Checkpoint Activation Drives KP1019 Dependent Pre-Anaphase Cell Cycle Delay in S. cerevisiae. AB - Careful regulation of the cell cycle is required for proper replication, cell division, and DNA repair. DNA damage--including that induced by many anticancer drugs--results in cell cycle delay or arrest, which can allow time for repair of DNA lesions. Although its molecular mechanism of action remains a matter of debate, the anticancer ruthenium complex KP1019 has been shown to bind DNA in biophysical assays and to damage DNA of colorectal and ovarian cancer cells in vitro. KP1019 has also been shown to induce mutations and induce cell cycle arrest in Saccharomyces cerevisiae, suggesting that budding yeast can serve as an appropriate model for characterizing the cellular response to the drug. Here we use a transcriptomic approach to verify that KP1019 induces the DNA damage response (DDR) and find that KP1019 dependent expression of HUG1 requires the Dun1 checkpoint; both consistent with KP1019 DDR in budding yeast. We observe a robust KP1019 dependent delay in cell cycle progression as measured by increase in large budded cells, 2C DNA content, and accumulation of Pds1 which functions to inhibit anaphase. Importantly, we also find that deletion of RAD9, a gene required for the DDR, blocks drug-dependent changes in cell cycle progression, thereby establishing a causal link between the DDR and phenotypes induced by KP1019. Interestingly, yeast treated with KP1019 not only delay in G2/M, but also exhibit abnormal nuclear position, wherein the nucleus spans the bud neck. This morphology correlates with short, misaligned spindles and is dependent on the dynein heavy chain gene DYN1. We find that KP1019 creates an environment where cells respond to DNA damage through nuclear (transcriptional changes) and cytoplasmic (motor protein activity) events. PMID- 26375393 TI - Interactions between Financial and Environmental Networks in OECD Countries. AB - We analysed a multiplex of financial and environmental networks between OECD countries from 2002 to 2010. Foreign direct investments and portfolio investment showing the flows in equity securities, short-term, long-term and total debt, these securities represent the financial layers; emissions of NOx, PM10, SO2, CO2 equivalent and the water footprint associated with international trade represent the environmental layers. We present a new measure of cross-layer correlations between flows in different layers based on reciprocity. For the assessment of results, we implement a null model for this measure based on the exponential random graph theory. We find that short-term financial flows are more correlated with environmental flows than long-term investments. Moreover, the correlations between reverse financial and environmental flows (i.e. the flows of different layers going in opposite directions) are generally stronger than correlations between synergic flows (flows going in the same direction). This suggests a trade off between financial and environmental layers, where, more financialised countries display higher correlations between outgoing financial flows and incoming environmental flows than from lower financialised countries. Five countries are identified as hubs in this finance-environment multiplex: The United States, France, Germany, Belgium-Luxembourg and United Kingdom. PMID- 26375395 TI - Regarding "Emergency Physician Perceptions of Medically Unnecessary Advanced Diagnostic Imaging". PMID- 26375394 TI - Two of Them Do It Better: Novel Serum Biomarkers Improve Autoimmune Hepatitis Diagnosis. AB - BACKGROUND: Autoimmune hepatitis (AIH) is a chronic liver disease of unknown aetiology and characterized by continuing hepatocellular inflammation and necrosis. Autoantibodies represent accessible markers to measure the adaptive immune responses in the clinical investigation. Protein microarrays have become an important tool to discriminate the disease state from control groups, even though there is no agreed-upon standard to analyze the results. RESULTS: In the present study 15 sera of patients with AIH and 78 healthy donors (HD) have been tested against 1626 proteins by an in house-developed array. Using a Partial Least Squares Discriminant Analysis (PLS-DA) the resulting data interpretation led to the identification of both new and previously identified proteins. Two new proteins AHPA9419 and Chondroadherin precursor (UNQ9419 and CHAD, respectively), and previously identified candidates as well, have been confirmed in a validation phase by DELFIA assay using a new cohort of AIH patients. A receiver operating characteristic analysis was used for the evaluation of biomarker candidates. The sensitivity of each autoantigen in AIH ranged from 65 to 88%; moreover, when the combination of the two new autoantigens was analyzed, the sensitivity increased to 95%. CONCLUSIONS: Our findings demonstrate that the detection of autoantibodies against the two autoantigens could improve the performance in discriminating AIH patients from control classes and in combination with previously identified autoantigens and they could be used in diagnostic/prognostic markers. PMID- 26375396 TI - Identification of Gene-Expression Signatures and Protein Markers for Breast Cancer Grading and Staging. AB - The grade of a cancer is a measure of the cancer's malignancy level, and the stage of a cancer refers to the size and the extent that the cancer has spread. Here we present a computational method for prediction of gene signatures and blood/urine protein markers for breast cancer grades and stages based on RNA-seq data, which are retrieved from the TCGA breast cancer dataset and cover 111 pairs of disease and matching adjacent noncancerous tissues with pathologists-assigned stages and grades. By applying a differential expression and an SVM-based classification approach, we found that 324 and 227 genes in cancer have their expression levels consistently up-regulated vs. their matching controls in a grade- and stage-dependent manner, respectively. By using these genes, we predicted a 9-gene panel as a gene signature for distinguishing poorly differentiated from moderately and well differentiated breast cancers, and a 19 gene panel as a gene signature for discriminating between the moderately and well differentiated breast cancers. Similarly, a 30-gene panel and a 21-gene panel are predicted as gene signatures for distinguishing advanced stage (stages III-IV) from early stage (stages I-II) cancer samples and for distinguishing stage II from stage I samples, respectively. We expect these gene panels can be used as gene-expression signatures for cancer grade and stage classification. In addition, of the 324 grade-dependent genes, 188 and 66 encode proteins that are predicted to be blood-secretory and urine-excretory, respectively; and of the 227 stage-dependent genes, 123 and 51 encode proteins predicted to be blood-secretory and urine-excretory, respectively. We anticipate that some combinations of these blood and urine proteins could serve as markers for monitoring breast cancer at specific grades and stages through blood and urine tests. PMID- 26375397 TI - Basic Fibroblast Growth Factor Stimulates the Proliferation of Bone Marrow Mesenchymal Stem Cells in Giant Panda (Ailuropoda melanoleuca). AB - It has been widely known that the giant panda (Ailuropoda melanoleuca) is one of the most endangered species in the world. An optimized platform for maintaining the proliferation of giant panda mesenchymal stem cells (MSCs) is very necessary for current giant panda protection strategies. Basic fibroblast growth factor (bFGF), a member of the FGF family, is widely considered as a growth factor and differentiation inducer within the stem cell research field. However, the role of bFGF on promoting the proliferation of MSCs derived from giant panda bone marrow (BM) has not been reported. In this study, we aimed to investigate the role of bFGF on the proliferation of BM-MSCs derived from giant panda. MSCs were cultured for cell proliferation analysis at 24, 48 and 72 hrs following the addition of bFGF. With increasing concentrations of bFGF, cell numbers gradually increased. This was further demonstrated by performing 3-(4,5-dimethyl-2-thiazolyl)-2,5 diphenyl-2-H-tetrazolium bromide (MTT) cell proliferation assay, 5-Bromo-2 deoxyUridine (BrdU) labeling and cell cycle testing. Furthermore, the percentage of MSCs that were OCT4 positive increased slightly following treatment with 5 ng/ml bFGF. Moreover, we demonstrated that the extracellular signal-regulated kinase (ERK) signaling pathway may play an important role in the proliferation of panda MSCs stimulated by bFGF. In conclusion, this study suggests that giant panda BM-MSCs have a high proliferative capacity with the addition of 5 ng/ml bFGF in vitro. PMID- 26375399 TI - Glycosylations of Glycals using N-Iodosuccinimide (NIS) and Phosphorus Compounds for Syntheses of 2-Iodo- and 2-Deoxyglycosides. AB - The glycosylations of glycals and alcohols using N-iodosuccinimide (NIS) and a catalytic amount of PPh3 effectively proceeded under mild conditions to provide the corresponding 2-deoxy-2-iodoglycosides in high yields. The reactivity of the iodoglycosylations with PPh3 significantly increased in comparison to that using NIS alone as an activator. In addition, the glycosylations of glycals and alcohols using catalytic amounts of NIS and P(OPh)3 were effectively realized to give the corresponding 2-deoxyglycosides in high yields. PMID- 26375398 TI - Laryngeal High-Speed Videoendoscopy: Rationale and Recommendation for Accurate and Consistent Terminology. AB - PURPOSE: The authors discuss the rationale behind the term laryngeal high-speed videoendoscopy to describe the application of high-speed endoscopic imaging techniques to the visualization of vocal fold vibration. METHOD: Commentary on the advantages of using accurate and consistent terminology in the field of voice research is provided. Specific justification is described for each component of the term high-speed videoendoscopy, which is compared and contrasted with alternative terminologies in the literature. RESULTS: In addition to the ubiquitous high-speed descriptor, the term endoscopy is necessary to specify the appropriate imaging technology and distinguish among modalities such as ultrasound, magnetic resonance imaging, and nonendoscopic optical imaging. Furthermore, the term video critically indicates the electronic recording of a sequence of optical still images representing scenes in motion, in contrast to strobed images using high-speed photography and non-optical high-speed magnetic resonance imaging. High-speed videoendoscopy thus concisely describes the technology and can be appended by the desired anatomical nomenclature such as laryngeal. CONCLUSIONS: Laryngeal high-speed videoendoscopy strikes a balance between conciseness and specificity when referring to the typical high-speed imaging method performed on human participants. Guidance for the creation of future terminology provides clarity and context for current and future experiments and the dissemination of results among researchers. PMID- 26375400 TI - Exercise-Induced Brugada Phenocopy. PMID- 26375401 TI - Epstein-Barr Virus MicroRNA Expression Increases Aggressiveness of Solid Malignancies. AB - The Cancer Genome Atlas (TCGA) microRNA (miRNA) initiative has revealed a pivotal role for miRNAs in cancer. Utilizing the TCGA raw data, we performed the first mapping of viral miRNA sequences within cancer and adjacent normal tissues. Results were integrated with TCGA RNA-seq to link the expression of viral miRNAs to the phenotype. Using clinical data and viral miRNA mapping results we also performed outcome analysis. Three lines of evidence lend credence to an active role of viral miRNAs in solid malignancies. First, expression of viral miRNA is consistently higher in cancerous compared to adjacent noncancerous tissues. Second, viral miRNA expression is associated with significantly worse clinical outcome among patients with early stage malignancy. These patients are also featured by increased expression of PD1/PD-L1, a pathway implicated in tumors escaping immune destruction. Finally, a particular cluster of EBV-miRNA (miR BART2, miR-BART4, miR-BART5, miR-BART18, and miR-BART22) is associated with expression of cytokines known to inhibit host response to cancer. Quantification of specific viral miRNAs may help identify patients who are at risk of poor outcome. These patients may be candidates for novel therapeutic strategies incorporating antiviral agents and/or inhibitors of the PD-1/PD-L1 pathway. PMID- 26375404 TI - Proteolysis and Flavor Characteristics of Serrano Ham Processed under Different Ripening Temperature Conditions. AB - Physicochemical, proteolysis and sensory characteristics of Serrano hams processed under low, medium and high ripening temperature conditions (RTC), with respective average temperatures of 9.3, 14.3, and 19.1 degrees C, were determined throughout a 15-mo period. In addition, quantitative relationships among variables were calculated. Medium and high RTC hams showed lower moisture contents and lower levels of low- and high-ionic-strength soluble proteins than low RTC hams. At 15 mo, aldolase was the most abundant low-ionic-strength soluble protein and actin the most abundant high-ionic-strength soluble protein in all hams while creatine kinase was no longer detected and H-meromyosin was detected only in low and medium RTC hams. Levels of all the molecular-weight peptide fractions increased during ripening, with higher factors of increase for the fractions of lower molecular weight. Total free amino acids were at significantly higher concentrations in medium and high RTC hams than in low RTC hams from month 7 onwards. The correlations of flavor preference and flavor intensity with ripening time, thermal integral, total free amino acids and most individual free amino acids were highly significant, while raw-meat taste was negatively correlated with all those variables. From month 5 to month 9 of ripening, development of a high quality flavor evolved more rapidly in medium RTC hams, flavor intensity increased at a faster rate in high RTC hams and raw-meat taste declined more rapidly in medium and high RTC hams. Medium and high RTC may be applied to accelerate the ripening process of Serrano ham without impairing flavor preference. PRACTICAL APPLICATION: Medium and high ripening temperature conditions (RTC) may be applied to Serrano ham in order to enhance the phenomena associated with ripening, without loss of product quality. Moisture loss, degradation of proteins and formation of free amino acids were accelerated in medium and high RTC hams. From month 5 to month 9 of ripening, development of a high quality flavor evolved more rapidly in medium RTC hams, flavor intensity increased at a faster rate in high RTC hams, and raw-meat taste declined more rapidly in medium and high RTC hams. PMID- 26375402 TI - Leucine-rich repeat kinase 2 interacts with p21-activated kinase 6 to control neurite complexity in mammalian brain. AB - Leucine-rich repeat kinase 2 (LRRK2) is a causative gene for Parkinson's disease, but the physiological function and the mechanism(s) by which the cellular activity of LRRK2 is regulated are poorly understood. Here, we identified p21 activated kinase 6 (PAK6) as a novel interactor of the GTPase/ROC domain of LRRK2. p21-activated kinases are serine-threonine kinases that serve as targets for the small GTP binding proteins Cdc42 and Rac1 and have been implicated in different morphogenetic processes through remodeling of the actin cytoskeleton such as synapse formation and neuritogenesis. Using an in vivo neuromorphology assay, we show that PAK6 is a positive regulator of neurite outgrowth and that LRRK2 is required for this function. Analyses of post-mortem brain tissue from idiopathic and LRRK2 G2019S carriers reveal an increase in PAK6 activation state, whereas knock-out LRRK2 mice display reduced PAK6 activation and phosphorylation of PAK6 substrates. Taken together, these results support a critical role of LRRK2 GTPase domain in cytoskeletal dynamics in vivo through the novel interactor PAK6, and provide a valuable platform to unravel the mechanism underlying LRRK2 mediated pathophysiology. We propose p21-activated kinase 6 (PAK6) as a novel interactor of leucine-rich repeat kinase 2 (LRRK2), a kinase involved in Parkinson's disease (PD). In health, PAK6 regulates neurite complexity in the brain and LRRK2 is required for its function, (a) whereas PAK6 is aberrantly activated in LRRK2-linked PD brain (b) suggesting that LRRK2 toxicity is mediated by PAK6. PMID- 26375403 TI - C-Mpl Is Expressed on Osteoblasts and Osteoclasts and Is Important in Regulating Skeletal Homeostasis. AB - C-Mpl is the receptor for thrombopoietin (TPO), the main megakaryocyte (MK) growth factor, and c-Mpl is believed to be expressed on cells of the hematopoietic lineage. As MKs have been shown to enhance bone formation, it may be expected that mice in which c-Mpl was globally knocked out (c-Mpl(-/-) mice) would have decreased bone mass because they have fewer MKs. Instead, c-Mpl(-/-) mice have a higher bone mass than WT controls. Using c-Mpl(-/-) mice we investigated the basis for this discrepancy and discovered that c-Mpl is expressed on both osteoblasts (OBs) and osteoclasts (OCs), an unexpected finding that prompted us to examine further how c-Mpl regulates bone. Static and dynamic bone histomorphometry parameters suggest that c-Mpl deficiency results in a net gain in bone volume with increases in OBs and OCs. In vitro, a higher percentage of c-Mpl(-/-) OBs were in active phases of the cell cycle, leading to an increased number of OBs. No difference in OB differentiation was observed in vitro as examined by real-time PCR and functional assays. In co-culture systems, which allow for the interaction between OBs and OC progenitors, c-Mpl(-/-) OBs enhanced osteoclastogenesis. Two of the major signaling pathways by which OBs regulate osteoclastogenesis, MCSF/OPG/RANKL and EphrinB2-EphB2/B4, were unaffected in c-Mpl(-/-) OBs. These data provide new findings for the role of MKs and c-Mpl expression in bone and may provide insight into the homeostatic regulation of bone mass as well as bone loss diseases such as osteoporosis. PMID- 26375405 TI - Ultrastructural investigation on fibroblast interaction with collagen scaffold. AB - Collagen-based scaffolds are used as temporary or permanent coverings to help wound healing. Under natural conditions, wound healing is affected by such factors as cell types, growth factors and several components of the extracellular matrix. Due to the complexity of the cell-to-matrix interaction, many cell based mechanisms regulating wound healing in vivo are not yet properly understood. However, the whole process can be partially simulated in vitro to determine how cells interact with the collagen scaffold in relation to such features as physico chemical properties, matrix architecture and fiber stability. Under these conditions, cell migration into the collagen matrix can be easily assessed and causally correlated with these features. In this study, we aimed at providing a structural analysis of how NIH3T3 fibroblasts migrate and proliferate in vitro when seeded on a native type-I collagen scaffold. To this end, samples were collected at regular time intervals and analyzed by light microscopy (LM), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Through this experimental approach we demonstrate that collagen is gradually frayed into progressively thinner fibrils as fibroblasts migrate into the matrix, embrace the collagen fibers with long filopodia and form large intracellular vacuoles. A key role in this process is also played by microvesicles shed from the fibroblast plasma membrane and spread over long distances inside the collagen matrix. These observations indicate that a native type-I equine collagen provides favorable conditions for simulating collagen processing in vitro and eventually for unraveling the mechanisms controlling cell uptake and intracellular degradation. PMID- 26375406 TI - Optimization of Cadmium (CD(2+)) removal from aqueous solutions by novel biosorbent. AB - In this research, dead leaves of a common ornamental plant, Dracaena draca known also as dragon tree was used as a biosorbent for the removal of Cadmium (Cd(2+)) from aqueous solutions using a full 2(3) factorial experimental design. Three factors were investigated at two different levels, metal ion concentration (X = 10 and 100 ppm), hydrogen ion concentration (Ph = 2 and 7) and biomass dose (BD = 0.1 and 0.5g). Experiments were carried out in duplicates with 50 ml of Cd(2+) solutions at room temperature. When comparing observed values (experimental) with calculated values (model), they were set closely together that allowed suggesting a normal distribution where (R(2) = 0.9938). A characterization of the biosorbent was done by pHzpc and SEM-EDAX. Results also showed that the most significant effect for Cd(2+) biosorption was ascribed to (X). The interaction effects of (pH BD) and (X pH) were found to have significant influence on Cd(2+) removal efficiency. The highest Cd(2+) removal percentage attained by 79.60% at X = 10 ppm, pH = 7 and BD = 0.5g. The reusability of the biosorbent was tested in three desorption cycles and the regeneration efficiency was above 99.7%. PMID- 26375407 TI - Key strategic factors for stakeholders in the current global biosimilar market. AB - What are the strategies of success in the global biosimilar market? In general, originators have short-term options available, such as patent litigation, but should focus on sustainable long-term strategies such as development of biobetters or incorporating biosimilars as complements to existing products. For new entrants to the market, the learning curve will be steep and only biosimilars developed to compete with the best-selling biologics will be successful over the next decade. The attitudes of physicians, patients and payers will be crucial to the reception future biosimilars will receive and it will be essential that other players contribute to this debate. PMID- 26375409 TI - Clinical Research Abstracts of the British Equine Veterinary Association Congress 2015. AB - REASONS FOR PERFORMING STUDY: The morphology of the dorsal (DCB) and ventral (VCB) nasal conchal bullae, including their cellulae, drainage and histology, are poorly described. The recent recognition that these bullae can become infected, causing chronic unilateral nasal discharge has stimulated interest in these structures. A more complete understanding of their anatomy would be useful in the diagnosis and treatment of their disorders. OBJECTIVES: To document the structure, drainage and histology of the equine DCB and VCB. STUDY DESIGN: Descriptive. METHODS: Fourteen fresh cadaveric horse heads, were transected sagittally midline and dissected to expose the nasal conchal bullae. The dimensions of each bulla, the number of drainage apertures, the number of cellulae and orientation of the septae were recorded. Representative samples were collected for histopathology. RESULTS: The mean lengths of the DCB and VCB were 77.7 mm (range 48-105 mm) and 57.1 mm (range 34-86 mm) respectively; equivalent to 13.8% and 10.2% of skull length, respectively. The mean widths of the DCB and VCB were 28.5 mm (range 21-35 mm) and 28.2 mm (range 13-41 mm) respectively; equivalent to 5.1% and 5% of skull length respectively. The median number of drainage apertures from the DCB and VCB were 2 and 1 respectively. The median number of cellulae within the DCB and VCB were 3 and 2, respectively. No communications were identified between the DCB and VCB and the adjacent paranasal sinuses. Histology revealed that the bullae consisted of ciliated, pseudostratified, columnar epithelium supported by a glandular submucosa often overlying turbinate bone and, variably, hyaline cartilage. CONCLUSIONS: The morphology of the equine nasal conchal bullae is quite variable. The DCB is generally a more complex structure than the VCB, containing more septae, cellulae and drainage apertures. This more detailed description of DCB and VCB anatomy will hopefully facilitate successful treatment of their disorders. Ethical animal research: Research ethics committee oversight not currently required by this conference: the study was performed on material obtained from an abattoir. SOURCE OF FUNDING: None. Competing interests: None declared. PMID- 26375408 TI - Identification of the putative binding pocket of valerenic acid on GABAA receptors using docking studies and site-directed mutagenesis. AB - BACKGROUND AND PURPOSE: beta2/3-subunit-selective modulation of GABAA receptors by valerenic acid (VA) is determined by the presence of transmembrane residue beta2/3N265. Currently, it is not known whether beta2/3N265 is part of VA's binding pocket or is involved in the transduction pathway of VA's action. The aim of this study was to clarify the localization of VA's binding pocket on GABAA receptors. EXPERIMENTAL APPROACH: Docking and a structure-based three-dimensional pharmacophore were employed to identify candidate amino acid residues that are likely to interact with VA. Selected amino acid residues were mutated, and VA induced modulation of the resulting GABAA receptors expressed in Xenopus oocytes was analysed. KEY RESULTS: A binding pocket for VA at the beta(+) /alpha(-) interface encompassing amino acid beta3N265 was predicted. Mutational analysis of suggested amino acid residues revealed a complete loss of VA's activity on beta3M286W channels as well as significantly decreased efficacy and potency of VA on beta3N265S and beta3F289S receptors. In addition, reduced efficacy of VA induced IGABA enhancement was also observed for alpha1M235W, beta3R269A and beta3M286A constructs. CONCLUSIONS AND IMPLICATIONS: Our data suggest that amino acid residues beta3N265, beta3F289, beta3M286, beta3R269 in the beta3 subunit, at or near the etomidate/propofol binding site(s), form part of a VA binding pocket. The identification of the binding pocket for VA is essential for elucidating its pharmacological effects and might also help to develop new selective GABAA receptor ligands. PMID- 26375410 TI - Lifestyle Intervention for Sleep Disturbances Among Overweight or Obese Individuals. AB - Little is known about the effect of different lifestyle interventions on sleep disturbances among sedentary obese or overweight persons. We randomized men and women aged 35-65 to 6 months of a weight loss diet (D); or D combined with supervised exercise training D + E. Measurements were self-reported sleep disturbances, the Profile of Mood States questionnaire, BMI, total abdominal subcutaneous and visceral fat by magnetic resonance imaging, and aerobic fitness expressed as VO2peak. The groups did not differ in changes for body weight, abdominal total fat, VO2peak, and sleep disturbances. The novel finding herein is that reduced abdominal subcutaneous fat and depressive symptoms, with either D or D + E were associated with less sleep disturbances. PMID- 26375411 TI - Staff Views of Acceptability and Appropriateness of a Computer-Delivered Brief Intervention for Moderate Drug and Alcohol Use. AB - The use of computers for identifying and intervening with stigmatized behaviors, such as drug use, offers promise for underserved, rural areas; however, the acceptability and appropriateness of using computerized brief intervention (CBIs) must be taken into consideration. In the present study, 12 staff members representing a range of clinic roles in two rural, federally qualified health centers completed semi-structured interviews in a qualitative investigation of CBI vs. counselor-delivered individual brief intervention (IBI). Thematic content analysis was conducted using a constant comparative method, examining the range of responses within each interview as well as data across interview respondents. Overall, staff found the idea of providing CBIs both acceptable and appropriate for their patient population. Acceptability by clinic staff centered on the ready availability of the CBI. Staff also believed that patients might be more forthcoming in response to a computer program than a personal interview. However, some staff voiced reservations concerning the appropriateness of CBIs for subsets of patients, including older patients, illiterate individuals, or those unfamiliar with computers. Findings support the potential suitability and potential benefits of providing CBIs to patients in rural health centers. PMID- 26375412 TI - CD4+CD28null T cells in acute coronary syndrome: lower with ST-elevation myocardial infarction. AB - OBJECTIVES: We explored any possible difference in the percentage of CD4 + CD28null T cells between patients with ST-segment-elevation myocardial infarction (STEMI) and those with non-ST-segment-elevation acute coronary syndrome. DESIGN: We enrolled 55 consecutive patients admitted with acute coronary syndrome, and 16 healthy control subjects. CD4 + CD28null T cell percentage was assayed by flow cytometry from blood samples withdrawn at the time of enrollment. RESULTS: Mean age was 55.2 +/- 10.8 years (69.1% males). Mean CD4 + CD28null T cell percentage was 5.9 +/- 3.8% in the study cohort versus 0.8 +/- 0.7% in controls (p < 0.001). Mean CD4 + CD28null T cell percentage was higher in patients presenting with non ST-segment-elevation acute coronary syndrome versus those presenting with STEMI: 7.3 +/- 4.1% versus 4.6 +/- 3.1%, respectively (p = 0.008). Multivariable regression analysis identified the category of acute coronary syndrome as the only variable independently associated with CD4 + CD28null T cell percentage (p = 0.007). CONCLUSIONS: In patients presenting with acute coronary syndrome, the CD4 + CD28null T cell percentage was higher in patients with non-ST-segment-elevation acute coronary syndrome versus those with STEMI. The category of acute coronary syndrome was the only variable independently associated with the CD4 + CD28null T cell percentage in multivariable regression analysis. PMID- 26375413 TI - The Role of Stem Cells in the Etiology and Pathophysiology of Endometriosis. AB - Human endometrium is a dynamic organ that normally undergoes repetitive cyclic regeneration. To enable this rapid regeneration, it is not surprising that the endometrium contains a reservoir of progenitor stem cells. However, this pool of cells that allows the growth of the endometrium also allows for unrestrained growth that can reach beyond the endometrium. In this review, we will address the role of stem cells in endometriosis. Recent characterization of stem cell populations within human endometrium has opened the possibility of understanding their physiologic as well as their pathologic roles. While stem cells are critical to the cyclic regeneration of a healthy endometrium, we have shown that both endometrium-derived and bone marrow-derived stem cells can migrate to ectopic sites and contribute to the development of endometriosis. Furthermore, endometriosis interferes with the normal stem cell trafficking to the uterus that is necessary for endometrial growth and repair. Altered stem cell mobility and engraftment characterize this disease. PMID- 26375414 TI - Neonatal vaccination with bacille Calmette-Guerin promotes the dendritic development of hippocampal neurons. AB - Dendritic structure is sensitive to changes in the environment during brain development. Accumulating evidence has demonstrated that early immune activation can significantly affect neuronal development. Our study concentrated on the morphological study of neural dendrites and spines in the hippocampal CA1 area using Diolistic labeling with Sholl analysis and fractal analysis. The results revealed that Bacille Calmette-Guerin (BCG) vaccination enhanced dendritic complexity, as reflected by the increased number of intersections, number of branch points and fractal dimension, and promoted neurite outgrowth. In addition, BCG increased the density and promoted the maturation of dendritic spines. The alterations in dendritic structure and spine morphology were observed at 2 and 4 w, but the differences were more apparent at 4 w than at 2 w. However, no significant difference was observed at 8 w. Furthermore, we observed that BCG increased the expression of hippocampal brain derived neurotrophic factor (BDNF) and insulin-like growth factor 1 (IGF-1). Hippocampal BDNF/IGF-1 was positively correlated with apical dendritic length, fractal dimension, and spine density. Taken together, we show in this study that neonatal BCG vaccination promotes dendritic development in developing hippocampal CA1 neurons, most likely by increasing the expression of BDNF and IGF-1 in the hippocampus. PMID- 26375415 TI - EUS and EUS-FNA diagnosis of suspected pancreatic cystic neoplasms: Is the sum of the parts greater than the CEA? AB - BACKGROUND: Carcinoembryonic antigen (CEA) is suggested as the single most useful EUS/EUS-FNA derived test for the diagnosis of mucinous pancreatic cysts. STUDY AIMS: To investigate the yield and diagnostic performance of EUS/EUS-FNA on an intention to diagnose basis and to determine the utility of the recommended CEA and amylase cut-off values. PATIENTS AND METHODS: A retrospective study of a prospectively maintained database of 433 procedures performed in a 10 year period. Diagnostic performance of EUS-FNA was determined in 133 procedures with a definite diagnosis. RESULTS: CEA value was determined in significantly fewer procedures (58.6%) than EUS diagnosis was stated (83.4%; p < 0.0001), cyst fluid appearance recorded (89.4%) or adequate sample for cytology obtained (76.7%; p < 0.005). Median CEA was significantly higher in mucinous cysts than non-mucinous (175 ng/ml vs 3 ng/ml, p < 0.0001) and in malignant cysts compared to benign (8945 ng/ml vs 93 ng/ml, p < 0.001). On an intention-to-diagnose analysis, a CEA cut-off of 110 ng/ml was significantly less accurate (42.8%) than EUS diagnosis (67.7%), cytology (58.6%) or aspirate appearance (66.9%; p < 0.05 for all comparisons). However, the combination of EUS diagnosis, cytology and CEA provided higher sensitivity (91%), specificity (75%) and accuracy (85.7%) than each component test alone (p < 0.05 for all comparisons). Median amylase was significantly higher in benign compared to high-risk mucinous cysts ((11,429IU/L vs. 113IU/L; p < 0.05. CONCLUSION: The combination of EUS, cytology and CEA performed well. Malignant cysts had a higher CEA value than benign cysts. On an intention to diagnose basis a CEA cut-off of 110 ng/ml performed poorly. PMID- 26375416 TI - Probing the gel to liquid-crystalline phase transition and relevant conformation changes in liposomes by (13)C magic-angle spinning NMR spectroscopy. AB - A straightforward way to visualize gel to liquid-crystalline phase transition in phospholipid membranes is presented by using 13C magic-angle spinning NMR. The changes in the 13C isotropic chemical shifts with increasing temperature are shown to be a sensitive probe of the main thermotropic phase transition related to lipid hydrocarbon chain dynamics and relevant conformational changes. The average value of the energy difference between trans and gauche states in the central C4-11 fragment of the DMPC acyl chain was estimated to be 4.02 +/- 0.2 kJ mol-1 in the liquid crystalline phase. The reported spectral features will be useful in 13C solid state NMR studies for direct monitoring of the effective lipid chain melting allowing rapid uniaxial rotation of membrane proteins in the biologically relevant liquid-crystalline phase. PMID- 26375419 TI - Report of the 48th Annual Meeting of the Pacific Association of Pediatric Surgeons, Jeju, South Korea, May 17th-21st, 2015. AB - This is the report of the 48th Annual Meeting of the Pacific Association of Pediatric Surgeons held at the Shilla Hotel, Jeju Island, South Korea, May 17th 21st, 2015. PMID- 26375420 TI - Fluorescent metal ion chemosensors via cation exchange reactions of complexes, quantum dots, and metal-organic frameworks. AB - Due to their wide range of applications and biological significance, fluorescent sensors have been an active research area in the past few years. In the present review, recent research developments on fluorescent chemosensors that detect metal ions via cation exchange reactions (transmetalation, metal displacement, or metal exchange reactions) of complexes, quantum dots, and metal-organic frameworks are described. These complex-based chemosensors might have a much better selectivity than the corresponding free ligands/receptors because of the shielding function of the filled-in metal ions. Moreover, not only the chemical structure of the ligands/receptors but also the identity of the central metal ions have a tremendous impact on the sensing performances. Therefore, sensing via cation exchange reactions potentially provides a new, simple, and powerful way to design fluorescent chemosensors. PMID- 26375417 TI - Assembling the puzzle: Oligomerization of alpha-pore forming proteins in membranes. AB - Pore forming proteins (PFPs) share the ability of creating pores that allow the passage of ions, proteins or other constituents through a wide variety of target membranes, ranging from bacteria to humans. They often cause cell death, as pore formation disrupts the membrane permeability barrier required for maintaining cell homeostasis. The organization into supramolecular complexes or oligomers that pierce the membrane is a common feature of PFPs. However, the molecular pathway of self-assembly and pore opening remains unclear. Here, we review the most recent discoveries in the mechanism of membrane oligomerization and pore formation of a subset of PFPs, the alpha-PFPs, whose pore-forming domains are formed by helical segments. Only now we are starting to grasp the molecular details of their function, mainly thanks to the introduction of single molecule microscopy and nanoscopy techniques. This article is part of a Special Issue entitled: Pore-forming toxins edited by Mauro Dalla Serra and Franco Gambale. PMID- 26375421 TI - Impact of Early Postnatal NSAID Treatment on Nephrogenesis in Wistar Rats. AB - BACKGROUND: Prematurely born children with patent ductus arteriosus are treated with ibuprofen or indomethacin, which may inhibit kidney development. We determined whether clinical doses affected kidney development and function, with or without extrauterine growth retardation. METHODS: Wistar rats were cross fostered in normal food (NF) or food restricted (FR) litters at postnatal day (PND) 2. On PND 3 to 4, three doses of 0.9% NaCl, 0.1 mg/kg indomethacin, or 10 mg/kg ibuprofen were administered via intraperitoneal injection with 12-hr intervals. Kidneys were evaluated for apoptosis, proliferation, and gene expression at PND 8; stereological assessment of nephron number at PND 35; and clinical pathology and neutrophil gelatinase-associated lipocalin at 4 and 9 months. Blood pressure was measured at the ages of 4, 6, and 9 months. RESULTS: NF and FR bodyweight differed from PND 3 onwards, ranging from 16.5 g at weaning (p < 0.001) to 39 g at necropsy (p = 0.019). Kidney proliferation/apoptosis ratios were 7:1 and 3:1 (p = 0.001), respectively and different expression of Wnt4 (0.7x), Oat1 (1.3x), Nphs1 (1.7x), and Aqp4 (1.3x) was noted (but its biological relevance doubted). Nephron numbers were decreased by 12% (p = 0.109) in the ibuprofen-NF group and 7.5% (p = 0.237) in FR groups. This coincided with a tendency to increased neutrophil gelatinase-associated lipocalin at 9 months. No differences were noted in electrolytes, creatinine, or urea clearance. No valid blood pressure results could be obtained. CONCLUSION: A clinical Ibuprofen dose showed potential to inhibit kidney development in neonatal rats. FR did not modulate these effects. PMID- 26375423 TI - Fibromyalgia beyond reductionism. Heart rhythm fractal analysis to assess autonomic nervous system resilience. AB - OBJECTIVES: The prevailing linear reductionist medical model seems unable to explain complex multisymptomatic illnesses such as fibromyalgia (FM) and similar maladies. Paradigms derived from the complexity theory may provide a coherent framework for these elusive illnesses. Along these lines is the proposal that FM represents a degradation of our main complex adaptive system (the autonomic nervous system, ANS), in a failed effort to adjust to a hostile environment. Healthy complex systems have fractal structures. Heart rate fractal-like variability reflects resilient ANS performance. Our aim was to measure the heart rate variability (HRV) fractal scaling index in FM patients and to correlate this index with clinical symptoms. METHOD: We studied 30 women with FM and 30 controls. All participants filled out questionnaires assessing the severity of FM. The HRV fractal scaling index was estimated during 24 h using detrended fluctuation analysis (DFA). RESULTS: The fractal scaling index alpha-1 was higher in FM patients than in controls (mean +/- sd: 1.22 +/- 0.10 vs. 1.16 +/- 0.09; p = 0.031). There was a positive correlation between the fractal scaling index alpha-1 and the visual analogue scale (VAS) for depression (Spearman's rho = 0.36, p = 0.04). CONCLUSIONS: The heart rate fractal exponent alpha-1 is altered in FM patients, suggesting a rigid ANS performance. This tangible non-linear finding supports the notion that FM may represent a degradation of our main complex adaptive system, namely the ANS. PMID- 26375422 TI - Component Separation vs. Bridged Repair for Large Ventral Hernias: A Multi Institutional Risk-Adjusted Comparison, Systematic Review, and Meta-Analysis. AB - BACKGROUND: Repair of large ventral hernia defects is associated with high rates of surgical site occurrences (SSO), including surgical site infection (SSI), site dehiscence, seroma, hematoma, and site necrosis. Two common operative strategies exist: Component separation (CS) with primary fascial closure and mesh reinforcement (PFC-CS) and bridged repair (mesh spanning the hernia defect). We hypothesized that: (1) ventral hernia repair (VHR) of large defects with bridged repair is associated with more SSOs than is PFC, and (2) anterior CS is associated with more SSOs than is endoscopic, perforator-sparing, or posterior CS. METHODS: Part I of this study was a review of a multi-center database of patients who underwent VHR of a defect >=8 cm from 2010-2011 with at least one month of follow-up. The primary outcome was SSO. The secondary outcome was recurrence. Part II of this study was a systematic review and meta-analysis of studies comparing bridged repair with PFC and studies comparing different kinds of CS. RESULTS: A total of 108 patients were followed for a median of 16 months (range 1-50 months), of whom 84 underwent PFC-CS and 24 had bridged repairs. Unadjusted results demonstrated no differences between the groups in SSO or recurrence; however, the study was underpowered for this purpose. On meta analysis, PFC was associated with a lower risk of SSO (odds ratio [OR] = 0.569; 95% confidence interval [CI] = 0.34-0.94) and recurrence (OR = 0.138; 95% CI = 0.08-0.23) compared with bridged repair. On multiple-treatments meta-analysis, both endoscopic and perforator-sparing CS were most likely to be the treatments with the lowest risk of SSO and recurrence. CONCLUSIONS: Bridged repair was associated with more SSOs than was PFC, and PFC should be used whenever feasible. Endoscopic and perforator-sparing CS were associated with the fewest complications; however, these conclusions are limited by heterogeneity between studies and poor methodological quality. These results should be used to guide future trials, which should compare the risks and benefits of each CS method to determine in which setting each technique will give the best results. PMID- 26375424 TI - Novel application of luciferase assay for the in vitro functional assessment of KAL1 variants in three females with septo-optic dysplasia (SOD). AB - KAL1 is implicated in 5% of Kallmann syndrome cases, a disorder which genotypically overlaps with septo-optic dysplasia (SOD). To date, a reporter based assay to assess the functional consequences of KAL1 mutations is lacking. We aimed to develop a luciferase assay for novel application to functional assessment of rare KAL1 mutations detected in a screen of 422 patients with SOD. Quantitative analysis was performed using L6-myoblasts stably expressing FGFR1, transfected with a luciferase-reporter vector containing elements of the FGF responsive osteocalcin promoter. The two variants assayed [p.K185N, p.P291T], were detected in three females with SOD (presenting with optic nerve hypoplasia, midline and pituitary defects). Our novel assay revealed significant decreases in transcriptional activity [p.K185N: 21% (p < 0.01); p.P291T: 40% (p < 0.001)]. Our luciferase-reporter assay, developed for assessment of KAL1 mutations, determined that two variants in females with hypopituitarism/SOD are loss-of-function; demonstrating that this assay is suitable for quantitative assessment of mutations in this gene. PMID- 26375426 TI - Pathological calcification and the mystery of Lot's wife. PMID- 26375425 TI - The ERalpha-PI3K Cascade in Proopiomelanocortin Progenitor Neurons Regulates Feeding and Glucose Balance in Female Mice. AB - Estrogens act upon estrogen receptor (ER)alpha to inhibit feeding and improve glucose homeostasis in female animals. However, the intracellular signals that mediate these estrogenic actions remain unknown. Here, we report that anorexigenic effects of estrogens are blunted in female mice that lack ERalpha specifically in proopiomelanocortin (POMC) progenitor neurons. These mutant mice also develop insulin resistance and are insensitive to the glucose-regulatory effects of estrogens. Moreover, we showed that propyl pyrazole triol (an ERalpha agonist) stimulates the phosphatidyl inositol 3-kinase (PI3K) pathway specifically in POMC progenitor neurons, and that blockade of PI3K attenuates propyl pyrazole triol-induced activation of POMC neurons. Finally, we show that effects of estrogens to inhibit food intake and to improve insulin sensitivity are significantly attenuated in female mice with PI3K genetically inhibited in POMC progenitor neurons. Together, our results indicate that an ERalpha-PI3K cascade in POMC progenitor neurons mediates estrogenic actions to suppress food intake and improve insulin sensitivity. PMID- 26375427 TI - Application of statistical shape analysis for the estimation of bone and forensic age using the shapes of the 2nd, 3rd, and 4th cervical vertebrae in a young Japanese population. AB - OBJECTIVE: From computed tomographic images, the dentocentral synchondrosis can be identified in the second cervical vertebra. This can demarcate the border between the odontoid process and the body of the 2nd cervical vertebra and serve as a good model for the prediction of bone and forensic age. Nevertheless, until now, there has been no application of the 2nd cervical vertebra based on the dentocentral synchondrosis. METHODS: In this study, statistical shape analysis was used to build bone and forensic age estimation regression models. Following the principles of statistical shape analysis and principal components analysis, we used cone-beam computed tomography (CBCT) to evaluate a Japanese population (35 males and 45 females, from 5 to 19 years old). RESULTS: The narrowest prediction intervals among the multivariate regression models were 19.63 for bone age and 2.99 for forensic age. There was no significant difference between form space and shape space in the bone and forensic age estimation models. However, for gender comparison, the bone and forensic age estimation models for males had the higher explanatory power. CONCLUSION: This study derived an improved objective and quantitative method for bone and forensic age estimation based on only the 2nd, 3rd and 4th cervical vertebral shapes. PMID- 26375428 TI - Assessment of identity during adolescence using daily diary methods: Measurement invariance across time and sex. AB - The aim of this study was to assess measurement invariance of adolescents' daily reports on identity across time and sex. Adolescents (N = 497; mean age = 13.32 years at Time 1, 56.7% boys) from the general population reported on their identity commitments, exploration in depth and reconsideration on a daily basis for 3 weeks within 1 year across 5 years. We used the single-item version of the Utrecht Management of Identity Commitments Scale (UMICS; Klimstra et al., 2010), a broad measure of identity-formation processes covering both interpersonal and educational identity domains. This study tested configural, metric, scalar, and strict measurement invariance across days within weeks, across sex, across weeks within years, and across years. Results indicated that daily diary reports show strict measurement invariance across days, across weeks within years, across years, and across boys and girls. These results support the use of daily diary methods to assess identity at various time intervals ranging from days to years and across sex. Results are discussed with regard to future implications to study identity processes, both on smaller and larger time intervals. (PsycINFO Database Record PMID- 26375429 TI - Psychometric properties of a brief version of the Penn State Worry Questionnaire in African Americans and European Americans. AB - The reliable and valid assessment of chronic worry in African Americans is vital when attempting to draw cross-cultural comparisons between African Americans and other ethnic groups. As such, the current study examined the psychometric properties of a brief version of a gold standard assessment of chronic worry, specifically the Penn State Worry Questionnaire-Abbreviated (PSWQ-A; Hopko et al., 2003) in a college sample of African Americans (n = 100) and European Americans (n = 121). Results indicated that the PSWQ-A total score has good internal consistency and convergent validity with another measure of anxiety, but less than favorable discriminant validity with a measure of depression in African American and European American students. Also, the 1-factor solution for the 8 item PSWQ-A had excellent model fit in our full sample and was partially invariant between ethnic groups. Collectively, the present study provides evidence that the PSWQ-A is a psychometrically sound option for assessing chronic worry and suggests that this brief measure may enhance the time efficiency and clinical utility of research and clinical assessments in ethnically diverse samples. (PsycINFO Database Record PMID- 26375430 TI - Reliability and validity of the Danish version of the Schema Mode Inventory (SMI). AB - Schema modes are conceptualized as different parts of oneself, related to specific emotions, cognitions, and behaviors. They are a central concept in schema therapy for personality pathology and other chronic psychiatric disorders. Prior research confirms the factorial validity of the Schema Mode Inventory (SMI), an instrument to assess schema modes. This study presents an evaluation of the Danish version of the SMI, including reliability and validity analyses. Psychometric properties, such as factor structure, internal reliability, as well as intercorrelations between subscales were assessed. This was done on the basis of a mixed Danish sample (N = 657; M age = 29.32 years; range = 18-66 years; 78.5% females) composed of 266 clinical and 391 nonclinical adult participants. Results indicated model fit for the 14-factor structure of the SMI and adequate to excellent internal reliabilities of the 14 subscales (Cronbach's alpha =.74 .96). Furthermore, the SMI scales differentiated between clinical and nonclinical participants as theoretically predicted. These findings imply that the SMI is a sound instrument to measure the schema mode model in a Danish setting, both for clinical and research purposes, and in particular for assessment prior to schema therapy. PMID- 26375431 TI - Amanita phalloides poisoning: Mechanisms of toxicity and treatment. AB - Amanita phalloides, also known as 'death cap', is one of the most poisonous mushrooms, being involved in the majority of human fatal cases of mushroom poisoning worldwide. This species contains three main groups of toxins: amatoxins, phallotoxins, and virotoxins. From these, amatoxins, especially alpha amanitin, are the main responsible for the toxic effects in humans. It is recognized that alpha-amanitin inhibits RNA polymerase II, causing protein deficit and ultimately cell death, although other mechanisms are thought to be involved. The liver is the main target organ of toxicity, but other organs are also affected, especially the kidneys. Intoxication symptoms usually appear after a latent period and may include gastrointestinal disorders followed by jaundice, seizures, and coma, culminating in death. Therapy consists in supportive measures, gastric decontamination, drug therapy and, ultimately, liver transplantation if clinical condition worsens. The discovery of an effective antidote is still a major unsolved issue. The present paper examines the clinical toxicology of A. phalloides, providing the currently available information on the mechanisms of toxicityinvolved and on the current knowledge on the treatment prescribed against this type of mushrooms. Antidotal perspectives will be raised as to set the pace to new and improved therapy against these mushrooms. PMID- 26375432 TI - Gender differences in the prognostic role of uric acid and confounding factors. PMID- 26375433 TI - Abnormal distribution of AQP5 in labial salivary glands is associated with poor saliva secretion in patients with Sjogren's syndrome including neuromyelitis optica complicated patients. AB - OBJECTIVE: To investigate whether aquaporins (AQPs) are involved in salivary gland dysfunction in patients with neuromyelitis optica (NMO) complicated with Sjogren's syndrome (SS). METHODS: Eight primary SS (pSS) patients, four NMO spectrum disorder (NMOsd) patients complicated with SS (NMOsd-SS), and three control subjects were enrolled. Immunohistochemistry of labial salivary glands (LSGs) was performed to determine the expressions of AQP4, AQP5, and tumor necrosis factor-alpha (TNF-alpha). In vitro expression of AQP5 was examined by Western blotting in cultured primary salivary gland epithelial cells (SGECs). RESULTS: No expression of AQP4 was shown in all LSGs. AQP5 was clearly expressed in the all acini, but the predominant localization of AQP5 in the apical side was diminished in the patients with pSS or NMOsd-SS compared with the controls and tended to be even lower in NMOsd-SS than pSS. The abnormal localization of AQP5 was associated with poor saliva secretion. No difference was found in TNF-alpha expression in the LSGs between patients with pSS and NMOsd-SS. AQP5 expression of SGECs in vitro was not changed by TNF-alpha or interleukin-10. CONCLUSIONS: Our results suggest that AQP5 but not AQP4 contributes to salivary secretion in patients with SS including those with NMO complicated with SS. PMID- 26375434 TI - Flibanserin (Addyi) for hypoactive sexual desire disorder. PMID- 26375435 TI - "Hit the primary": A paradigm shift in the treatment of metastatic prostate cancer? AB - Patients with metastatic prostate cancer (PC) represent a heterogeneous group with survival rates varying between 13 and 75 months. The current standard treatment in this setting is hormonal therapy, with or without docetaxel-based chemotherapy. In the era of individualized medicine, however, maximizing treatment options, especially in long-term surviving patients with limited disease burden, is of capital importance. Emerging data, mainly from retrospective surgical series, show survival benefits in men diagnosed with metastatic PC following definitive therapy for the prostate. Whether the irradiation of primary tumor in a metastatic disease might improve the therapeutic ratio in association with systemic treatments remains investigational. In this scenario, modern radiation therapy (RT) can play a significant role owing to its intrinsic capability to act as a more general immune response modifier, as well as to the potentially better toxicity profile compared to surgery. Preclinical data, clinical experience, and challenges in local treatment in de novo metastatic PC are reviewed and discussed. PMID- 26375436 TI - Career prospects and professional landscape after advanced endoscopy fellowship training: a survey assessing graduates from 2009 to 2013. AB - BACKGROUND AND AIMS: The advanced endoscopy (AE) fellowship is a popular career track for graduating gastroenterology fellows. The number of fellows completing AE fellowships and the number of programs offering this training have increased in the past 5 years. Despite this, we suspect that the number of AE attending (staff physician) positions have decreased (relative to the number of fellows graduating), raising concerns regarding AE job market saturation. Our aim was to survey practicing gastroenterology physicians who completed an AE fellowship within the past 5 years regarding their current professional status. METHODS: A 16-question survey was distributed using Research Electronic Data Capture by e mail to practicing gastroenterologists who completed an AE fellowship between 2009 and 2013. The survey questions elicited information regarding demographics, professional status, and additional information. RESULTS: A total of 96 invitations were distributed via e-mail. Forty-one of 96 respondents (43%) replied to the survey. Approximately half of the respondents were employed in an academic practice, with the remainder in private practice (56% and 44%, respectively). Nearly half (46%) of the respondents found it "difficult" to find an AE position after training. Thirty-nine percent of private-practice endoscopists were performing > 200 ERCPs/year, whereas 65% were doing so in academic settings (P = .09). Fifty-six percent of respondents were in small practices (0 to 1 partner), with a significantly smaller group size in private versus academic practice (72% versus 43%, P = .021). Seventy-eight percent of respondents believed the AE job market was saturated; most responded that the AE job market was saturated in both academic and private practice (44%), whereas 34% believed the job market was saturated in academics only. Most respondents (73%) who were training AE fellows found it difficult to place them in AE attending positions. Respondents from academic practice found it significantly more difficult to balance work and personal life compared with those in private practice (87% versus 33%, respectively; P = .0004). CONCLUSION: This index survey highlights the trends related to the current state of the post-AE fellowship professional landscape. Further evaluation and discussion are needed to address these evolving issues in professional practice in the field of gastroenterology. PMID- 26375437 TI - Underwater EMR of adenomas of the appendiceal orifice (with video). AB - BACKGROUND AND AIMS: EMR of adenomas involving the appendiceal orifice (AO) is controversial because of a high risk of perforation and incomplete resection. We evaluated the feasibility, safety, and outcomes of underwater EMR (UEMR) without submucosal injection for the treatment of adenomas involving the AO. METHODS: This was a prospective, observational study of a standardized UEMR technique without submucosal injection for adenomas involving the AO in 27 consecutive patients meeting inclusion and exclusion criteria. Surveillance colonoscopy included biopsy sampling of the EMR site and base of the AO. Main outcome measurements include technical success, histology, resection time, adverse events, and follow-up data. RESULTS: Over 42 months, UEMR of adenomas involving the AO (rim, 5 patients; inside, 22 patients) was attempted in 27 consecutive patients. Median adenoma size was 15 mm (range, 8 to 50). UEMR was successful in 24 patients (89%). Four patients were referred to surgery, 3 with UEMR failure because of an inability to exclude the adenoma extending into the appendix at the index procedure and 1 with invasive adenocarcinoma in the UEMR specimen. The median resection time was 3 minutes (range, 1 to 75). Adverse events consisted of postpolypectomy syndrome in 2 patients (7%). There was no perforation, bleeding requiring transfusion, or appendicitis. Final histology was tubular adenoma (7), tubulovillous adenoma (4), sessile serrated adenoma (15), and invasive adenocarcinoma (1). Twenty-one of 23 patients (91%), not referred to surgery, had follow-up colonoscopy with biopsy sampling of the resection site after a median of 29 weeks (range, 12 to 139) after resection. Residual adenoma was found in 2 of 21 patients (10%). CONCLUSION: On an intention-to-treat basis, UEMR without submucosal injection enabled safe and complete endoscopic resection of AO lesions. Close surveillance for residual or recurrence is warranted. ( CLINICAL TRIALS REGISTRATION NUMBER: NCT01750619.). PMID- 26375438 TI - Prognostic value of early response assessment using 18F-FDG PET/CT in chemotherapy-treated patients with non-small-cell lung cancer. AB - OBJECTIVE: We aimed to evaluate the prognostic value of early response assessment using a volumetric fluorine-18-fluorodeoxyglucose (F-FDG) PET analysis in chemotherapy-treated patients with non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: We retrospectively reviewed 33 patients with NSCLC who received first-line chemotherapy and performed F-FDG PET/computed tomography before (baseline PET) and after two cycles of chemotherapy (interim PET). The maximum standardized uptake value (SUVmax) and metabolic tumor volume (MTV) of the total malignant lesion were measured in baseline (SUV1 and MTV1) and interim (SUV2 and MTV2) PET images, and percentage changes in SUVmax (DeltaSUV) and MTV (DeltaMTV) were calculated between the two images. We compared PET parameters and clinicopathologic variables in terms of the 2-year overall survival (OS). RESULTS: The median follow-up period was 14.3 months and the 2-year OS was 31%. In PET images, the mean SUV1, MTV1, SUV2, MTV2, DeltaSUV, and DeltaMTV were 13.1+/-4.5, 307.9+/-340.0 cm, 9.5+/-5.1, 180.4+/-29.6 cm, 27+/-28%, and 42+/-65%, respectively. In univariable analysis, M stage, TNM stage, and all six PET parameters associated significantly with OS. Both the MTV1 and the DeltaMTV were tested against OS controlling for M stage, one at time, and the effect remained significant in multivariable analyses. CONCLUSION: A smaller baseline MTV and greater decrease in MTV between baseline and interim PET images are associated with a significantly prolonged OS. A volume-based F-FDG PET analysis would facilitate prediction of clinical outcome and identification of treatment resistant patients early during chemotherapy and could thus be used in personalized treatment approaches for patients with NSCLC. PMID- 26375439 TI - Gastrointestinal malignancies harbor actionable MET exon 14 deletions. AB - Recently, MET exon 14 deletion (METex14del) has been postulated to be one potential mechanism for MET protein overexpression. We screened for the presence of METex14del transcript by multiplexed fusion transcript analysis using nCounter assay followed by confirmation with quantitative reverse transcription PCR with correlation to MET protein expression by immunohistochemistry (IHC) and MET amplification by fluorescence in situ hybridization (FISH). We extracted RNAs from 230 patients enrolled onto the prospective molecular profiling clinical trial (NEXT-1) (NCT02141152) between November 2013 and August 2014. Thirteen METex14del cases were identified including 3 gastric cancer, 4 colon cancer, 5 non-small cell lung cancer, and one adenocarcinoma of unknown primary. Of these 13 METex14del cases, 11 were MET IHC 3+ and 2 were 2+. Only one out of the 13 METex14del cases was MET amplified (MET/CEP ratio > 2.0). Growths of two (gastric, colon) METex14del+ patient tumor derived cell lines were profoundly inhibited by both MET tyrosine kinase inhibitors and a monoclonal antibody targeting MET. In conclusion, METex14del is a unique molecular aberration present in gastrointestinal (GI) malignancies corresponding with overexpression of MET protein but rarely with MET amplification. Substantial growth inhibition of METex14del+ patient tumor derived cell lines by several MET targeting drugs strongly suggests METex14del is a potential actionable driver mutation in GI malignancies. PMID- 26375440 TI - miR-449a promotes liver cancer cell apoptosis by downregulation of Calpain 6 and POU2F1. AB - Our previous study shows that Calpain 6 (CAPN6) expression is regulated by PI3K Akt in liver cancer through POU2F1 and CAPN6 which promote cell proliferation and inhibit apoptosis of liver cancer cells. microRNAs (miRNAs) plays important roles in regulation of gene expression. However, whether miRNAs regulates CAPN6 expression and its cellular function is still unknown. This study aims to investigate how miRNAs regulate liver cancer apoptosis through POU2F1-CAPN6. It was verified that POU2F1 could promote cell proliferation and inhibit apoptosis through CAPN6. Using methods of bioinformatics, miR-449a was predicted as a potential regulator of both CAPN6 and POU2F1. It was verified that CAPN6 and POU2F1 were the target genes of miR-449a by luciferase assay. CAPN6 and POU2F1 protein and mRNA levels decreased in liver cancer cells with miR-449a overexpression using western blot and real time RT-PCR assays. miR-449a expression was lower in liver cancer tissues compared with their normal ones, so did the cells. Overexpression of miR-449a inhibited cell proliferation, induced G1 phase arrest and cell apoptosis in liver cancer. Further research demonstrated that miR-449a inhibited cancer cell proliferation and induced apoptosis via suppressing both POU2F1 and CAPN6. The study indicated that miR-449a functions as a tumor inhibitor in liver cancer by decreasing POU2F1 and CAPN6 expression in liver cancer. PMID- 26375441 TI - GOLPH3 is a potential therapeutic target and a prognostic indicator of poor survival in bladder cancer treated by cystectomy. AB - Golgi phosphoprotein 3 (GOLPH3) has been reported to be involved in the development of several human cancers. However, its clinical significance and biological role in bladder cancer remains unclear. In this study, we sought to analyze the GOLPH3 expression in bladder cancer samples and cells, and explore its clinical significance and biological role. We found that GOLPH3 was significantly increased in bladder cancer tissues and cells. Overexpression of GOLPH3 had significant correlation with poorer survival for bladder cancer patients treated by cystectomy. Knockdown of GOLPH3 inhibited the proliferation, migration and invasion of cancer cells, and tumor growth in a xenograft mouse model. GOLPH3 silencing inhibited AKT/m-TOR signaling, increased the cyclin dependent kinase (CDK) inhibitor p27 and decreased the CDK regulator cyclin D1 and matrix metallopeptidase 9 (MMP9). Thus, GOLPH3 is likely to play important roles in bladder cancer progression via modulating AKT/mTOR signaling, and it is a novel prognostic biomarker and promising therapeutic target for bladder cancer. PMID- 26375442 TI - Targeting of RUNX3 by miR-130a and miR-495 cooperatively increases cell proliferation and tumor angiogenesis in gastric cancer cells. AB - Mature microRNAs (miRNAs) are 21 to 23 nucleotide noncoding RNA molecules that can downregulate multiple gene expression by mRNA degradation or translational repression. miRNAs are considered to play important roles in cell proliferation, apoptosis, and differentiation during mammalian development. The Runt-related transcription factor 3 (RUNX3) expression and activity are frequently downregulated by various mechanisms in gastric cancer. We have reported that RUNX3 inactivation is crucial for early tumorigenesis. In this study, we investigated the role of miRNAs targeting RUNX3 in early tumorigenesis. miR-130a and miR-495 upregulated under hypoxic conditions that bind to the RUNX3 3' untranslated region (3'-UTR) were identified in gastric cancer cells by using microarray analysis and bioinformatics programs. Combination of miR-130a and miR 495 inhibited RUNX3 expression at the protein level, but not at the mRNA level. miR-130a and miR-495 significantly inhibited the RUNX3-3'UTR-luciferase activity. Combination of miR-130a and miR-495 significantly decreased apoptosis determined by Annexin V-FITC/propidium iodide staining and flow cytometric analysis, and the expression of Bim in SNU484 gastric cancer cells. In addition, p21 and Bim, RUNX3 target genes, were completely downregulated by the combination of miR-130a and miR-495. Using matrigel plug assay, we found that antagomiRs specific for miR 130a and miR-495 significantly reduced angiogenesis in vivo. In conclusion, targeting miR-130a and miR-495 could be a potential therapeutics to recover RUNX3 expression under hypoxic conditions and in early tumorigenic progression. PMID- 26375443 TI - Automated tracking of tumor-stroma morphology in microtissues identifies functional targets within the tumor microenvironment for therapeutic intervention. AB - Cancer-associated fibroblasts (CAFs) constitute an important part of the tumor microenvironment and promote invasion via paracrine functions and physical impact on the tumor. Although the importance of including CAFs into three-dimensional (3D) cell cultures has been acknowledged, computational support for quantitative live-cell measurements of complex cell cultures has been lacking. Here, we have developed a novel automated pipeline to model tumor-stroma interplay, track motility and quantify morphological changes of 3D co-cultures, in real-time live cell settings. The platform consists of microtissues from prostate cancer cells, combined with CAFs in extracellular matrix that allows biochemical perturbation. Tracking of fibroblast dynamics revealed that CAFs guided the way for tumor cells to invade and increased the growth and invasiveness of tumor organoids. We utilized the platform to determine the efficacy of inhibitors in prostate cancer and the associated tumor microenvironment as a functional unit. Interestingly, certain inhibitors selectively disrupted tumor-CAF interactions, e.g. focal adhesion kinase (FAK) inhibitors specifically blocked tumor growth and invasion concurrently with fibroblast spreading and motility. This complex phenotype was not detected in other standard in vitro models. These results highlight the advantage of our approach, which recapitulates tumor histology and can significantly improve cancer target validation in vitro. PMID- 26375444 TI - Integrated gene and miRNA expression analysis of prostate cancer associated fibroblasts supports a prominent role for interleukin-6 in fibroblast activation. AB - Tumor microenvironment coevolves with and simultaneously sustains cancer progression. In prostate carcinoma (PCa), cancer associated fibroblasts (CAF) have been shown to fuel tumor development and metastasis by mutually interacting with tumor cells. Molecular mechanisms leading to activation of CAFs from tissue resident fibroblasts, circulating bone marrow-derived fibroblast progenitors or mesenchymal stem cells are largely unknown. Through integrated gene and microRNA expression profiling, we showed that PCa-derived CAF transcriptome strictly resembles that of normal fibroblasts stimulated in vitro with interleukin-6 (IL6), thus proving evidence, for the first time, that the cytokine is able per se to induce most of the transcriptional changes characteristic of patient derived CAFs. Comparison with publicly available datasets, however, suggested that prostate CAFs may be alternatively characterized by IL6 and TGFbeta-related signatures, indicating that either signal, depending on the context, may concur to fibroblast activation. Our analyses also highlighted novel pathways potentially relevant for induction of a reactive stroma. In addition, we revealed a role for muscle-specific miR-133b as a soluble factor secreted by activated fibroblasts to support paracrine activation of non-activated fibroblasts or promote tumor progression.Overall, we provided insights into the molecular mechanisms driving fibroblast activation in PCa, thus contributing to identify novel hits for the development of therapeutic strategies targeting the crucial interplay between tumor cells and their microenvironment. PMID- 26375445 TI - MFG-E8, a clearance glycoprotein of apoptotic cells, as a new marker of disease severity in chronic obstructive pulmonary disease. AB - Milk fat globule epidermal growth factor 8 (MFG-E8) is an opsonin involved in the phagocytosis of apoptotic cells. In patients with chronic obstructive pulmonary disease (COPD), apoptotic cell clearance is defective. However, whether aberrant MFG-E8 expression is involved in this defect is unknown. In this study, we examined the expression of MFG-E8 in COPD patients. MFG-E8, interleukin (IL) 1beta and transforming growth factor (TGF)-beta levels were measured in the plasma of 96 COPD patients (93 males, 3 females; age range: 62.12+/-10.39) and 87 age-matched healthy controls (85 males, 2 females; age range: 64.81+/-10.11 years) using an enzyme-linked immunosorbent assay. Compared with controls, COPD patients had a significantly lower plasma MFG-E8 levels (P<0.01) and significantly higher plasma TGF-beta levels (P=0.002), whereas there was no difference in plasma IL-1beta levels between the two groups. Moreover, plasma MFG E8 levels decreased progressively between Global Initiative for Chronic Obstructive Lung Disease (GOLD) I and GOLD IV stage COPD. Multiple regression analysis showed that the forced expiratory volume in 1 s (FEV1 % predicted) and smoking habit were powerful predictors of MFG-E8 in COPD (P<0.01 and P=0.026, respectively). MFG-E8 was positively associated with the FEV1 % predicted and negatively associated with smoking habit. The area under the receiver operating characteristic curve was 0.874 (95% confidence interval: 0.798-0.95; P<0.01). Our findings demonstrated the utility of MFG-E8 as a marker of disease severity in COPD and that cigarette smoke impaired MFG-E8 expression in these patients. PMID- 26375446 TI - Specific alterations in plasma proteins during depressed, manic, and euthymic states of bipolar disorder. AB - Bipolar disorder (BD) is a common psychiatric mood disorder affecting more than 1 2% of the general population of different European countries. Unfortunately, there is no objective laboratory-based test to aid BD diagnosis or monitor its progression, and little is known about the molecular basis of BD. Here, we performed a comparative proteomic study to identify differentially expressed plasma proteins in various BD mood states (depressed BD, manic BD, and euthymic BD) relative to healthy controls. A total of 10 euthymic BD, 20 depressed BD, 15 manic BD, and 20 demographically matched healthy control subjects were recruited. Seven high-abundance proteins were immunodepleted in plasma samples from the 4 experimental groups, which were then subjected to proteome-wide expression profiling by two-dimensional electrophoresis and matrix-assisted laser desorption/ionization-time-of-flight/time-of-flight tandem mass spectrometry. Proteomic results were validated by immunoblotting and bioinformatically analyzed using MetaCore. From a total of 32 proteins identified with 1.5-fold changes in expression compared with healthy controls, 16 proteins were perturbed in BD independent of mood state, while 16 proteins were specifically associated with particular BD mood states. Two mood-independent differential proteins, apolipoprotein (Apo) A1 and Apo L1, suggest that BD pathophysiology may be associated with early perturbations in lipid metabolism. Moreover, down regulation of one mood-dependent protein, carbonic anhydrase 1 (CA-1), suggests it may be involved in the pathophysiology of depressive episodes in BD. Thus, BD pathophysiology may be associated with early perturbations in lipid metabolism that are independent of mood state, while CA-1 may be involved in the pathophysiology of depressive episodes. PMID- 26375447 TI - Overexpression of Salmonella enterica serovar Typhi recA gene confers fluoroquinolone resistance in Escherichia coli DH5alpha. AB - A spontaneous fluoroquinolone-resistant mutant (STM1) was isolated from its parent Salmonella enterica serovar Typhi (S. Typhi) clinical isolate. Unlike its parent isolate, this mutant has selective resistance to fluoroquinolones without any change in its sensitivity to various other antibiotics. DNA gyrase assays revealed that the fluoroquinolone resistance phenotype of the STM1 mutant did not result from alteration of the fluoroquinolone sensitivity of the DNA gyrase isolated from it. To study the mechanism of fluoroquinolone resistance, a genomic library from the STM1 mutant was constructed in Escherichia coli DH5alpha and two recombinant plasmids were obtained. Only one of these plasmids (STM1-A) conferred the selective fluoroquinolone resistance phenotype to E. coli DH5alpha. The chromosomal insert from STM1-A, digested with EcoRI and HindIII restriction endonucleases, produced two DNA fragments and these were cloned separately into pUC19 thereby generating two new plasmids, STM1-A1 and STM1-A2. Only STM1-A1 conferred the selective fluoroquinolone resistance phenotype to E. coli DH5alpha. Sequence and subcloning analyses of STM1-A1 showed the presence of an intact RecA open reading frame. Unlike that of the wild-type E. coli DH5alpha, protein analysis of a crude STM1-A1 extract showed overexpression of a 40 kDa protein. Western blotting confirmed the 40 kDa protein band to be RecA. When a RecA PCR product was cloned into pGEM-T and introduced into E. coli DH5alpha, the STM1-A11 subclone retained fluoroquinolone resistance. These results suggest that overexpression of RecA causes selective fluoroquinolone resistance in E. coli DH5alpha. PMID- 26375449 TI - The use of action phrases in individuals with Autism Spectrum Disorder. AB - Previous research has shown that individuals with Autism Spectrum Disorder (ASD) may be able to perceive the intentions of another individual through tool use (e.g., Aldridge et al., 2000; Gonzalez et al., 2013). However, it is not well understood how individuals with ASD respond to an indirect connection between an extrapolated action and the required object. To address this question, we employed action phrases that indirectly provided the contextual information about which object to use. Individuals with ASD, and sex and age matched typically developing peers, were asked to pick which object would be needed to complete the task described in a sentence displayed on a computer screen. Although individuals with ASD exhibited slower response times overall, their accuracy scores were comparable to typically developing individuals. The longer response times support the notion that individuals with ASD may have a harder time disengaging their initial perceived use for the object before considering other inherent action possibilities afforded by the object. PMID- 26375451 TI - Use of Long-Acting Somatostatin Analogue (Lanreotide) in an Adolescent with Diazoxide-Responsive Congenital Hyperinsulinism and Its Psychological Impact. AB - Congenital hyperinsulinism (CHI) is a common cause of hypoglycaemia due to unregulated insulin secretion from pancreatic beta cells. Medical management includes use of oral diazoxide (a KATP channel agonist) and daily injectable octreotide (somatostatin analogue) therapy. However, diazoxide is associated with severe sideeffects such as coarse facies, hypertrichosis and psychosocial/compliance issues in adolescents. Lanreotide (a long-acting somatostatin analogue) is used in adults with neuroendocrine tumours; however, its role in patients with CHI has not been well described. A 15-year-old girl with diazoxide-responsive CHI had severe hypertrichosis secondary to diazoxide and subsequent compliance/psychosocial issues. She was commenced on 30 mg of lanreotide every 4 weeks as a deep subcutaneous injection, in an attempt to address these issues. She was able to come off diazoxide treatment 2 months after starting lanreotide. Presently, after 2.5 years of lanreotide treatment, her blood glucose control is stable with complete resolution of hypertrichosis. Clinically significant improvements in the self-reported Paediatric Quality of Life (PedsQL) questionnaire and Strengths and Difficulties Questionnaire (SDQ) were reported after 1 year on lanreotide. No side effects were found, and her liver/thyroid function and abdominal ultrasound have been normal. We report the first case on the use of lanreotide in an adolescent girl with diazoxide responsive CHI with significant improvement of quality of life. PMID- 26375450 TI - Increasing the role of belief information in moral judgments by stimulating the right temporoparietal junction. AB - Morality plays a vital role in our social life. A vast body of research has suggested that moral judgments rely on cognitive processes mediated by the right temporoparietal junction (rTPJ), an area thought to be involved in belief attribution. Here we assessed the role of the rTPJ in moral judgments directly by means of transcranial direct current stimulation (tDCS)--a non-invasive brain stimulation technique that, by applying a weak current to the scalp, allows modulating cortical excitability of the area being stimulated. Participants were randomly and equally assigned to receive anodal stimulation (to increase cortical excitability), cathodal stimulation (to decrease cortical excitability), or sham (placebo) stimulation over the rTPJ before completing a moral judgment task. Participants read stories in which protagonists produced either a negative or a neutral outcome based on either a negative or a neutral belief that they were causing harm or no harm, respectively. Results revealed a selective group difference when judging the moral permissibility of accidental harms (belief neutral, outcome negative), but not intentional harms (belief negative, outcome negative), attempted harms (belief negative, outcome neutral), or neutral acts (belief neutral, outcome neutral). Specifically, participants who received anodal stimulation assigned less blame to accidental harms compared to participants who received cathodal or sham stimulation. These results are consistent with previous findings showing that the degree of rTPJ activation reflects reliance on the agent's innocent intention. Crucially, our findings provide direct evidence supporting the critical role of the rTPJ in mediating belief attribution for moral judgment. PMID- 26375452 TI - The legal status of suicide: A global review. AB - Copies were obtained of the criminal codes from 192 countries and states; in 25 suicide is currently illegal, and an additional 20 countries follow Islamic or Sharia law where suicide attempters may be punished with jail sentences. The vast majority of countries have laws making it illegal to abet, aid or encourage suicide, but the nature and punishment of the actions that are illegal varies. Laws in places with Civil, Common Law, Islamic Law and Traditional Law systems are compared. Great variances in application were noted, sometimes within countries. It is impossible to estimate the number of persons currently in jail for having attempted suicide, but jail sentences are still given to suicide attempters. Some countries do not prosecute suicide attempters despite the laws, while others consistently jail suicide attempters. In countries where suicide attempts have been decriminalized, attempters may still face prosecution when another person is injured or dies as a result of their suicide attempt or where the attempter is a member of the military. We discuss the roots of laws making suicide, aiding, and encouraging suicide illegal and examine prospects for future changes. The recent Supreme Court Decision in Canada, invalidating the law making it illegal to assist in the suicide of physically ill people who are suffering (abeit with restrictive conditions) illustrates current trends towards "liberalization" of assisted suicide. PMID- 26375453 TI - Exploring High Refractive Index Silicon-Rich Nitride Films by Low-Temperature Inductively Coupled Plasma Chemical Vapor Deposition and Applications for Integrated Waveguides. AB - Silicon-rich nitride films are developed and explored using an inductively coupled plasma chemical vapor deposition system at low temperature of 250 degrees C with an ammonia-free gas chemistry. The refractive index of the developed silicon-rich nitride films can increase from 2.2 to 3.08 at 1550 nm wavelength while retaining a near-zero extinction coefficient when the amount of silane increases. Energy dispersive spectrum analysis gives the silicon to nitrogen ratio in the films. Atomic force microscopy shows a very smooth surface, with a surface roughness root-mean-square of 0.27 nm over a 3 MUm * 3 MUm area of the 300 nm thick film with a refractive index of 3.08. As an application example, the 300 nm thick silicon-rich nitride film is then patterned by electron beam lithography and etched using inductively coupled plasma system to form thin-film micro/nano waveguides, and the waveguide loss is characterized. PMID- 26375454 TI - Single Amino Acid Polymorphisms of Pertussis Toxin Subunit S2 (PtxB) Affect Protein Function. AB - Whooping cough due to Bordetella pertussis is increasing in incidence, in part due to accumulation of mutations which increase bacterial fitness in highly vaccinated populations. Polymorphisms in the pertussis toxin, ptxA and ptxB genes, and the pertactin, prn genes of clinical isolates of Bordetella pertussis collected in Cincinnati from 1989 through 2005 were examined. While the ptxA and prn genotypes were variable, all 48 strains had the ptxB2 genotype; ptxB1 encodes glycine at amino acid 18 of the S2 subunit of pertussis toxin, while ptxB2 encodes serine. We investigated antigenic and functional differences of PtxB1 and PtxB2. The S2 protein was not very immunogenic. Only a few vaccinated or individuals infected with B. pertussis developed antibody responses to the S2 subunit, and these sera recognized both polymorphic forms equally well. Amino acid 18 of S2 is in a glycan binding domain, and the PtxB forms displayed differences in receptor recognition and toxicity. PtxB1 bound better to the glycoprotein, fetuin, and Jurkat T cells in vitro, but the two forms were equally effective at promoting CHO cell clustering. To investigate in vivo activity of Ptx, one MUg of Ptx was administered to DDY mice and blood was collected on 4 days after injection. PtxB2 was more effective at promoting lymphocytosis in mice. PMID- 26375456 TI - Histological Analysis of Intra-Abdominal Adhesions Treated with Sodium Hyaluronate and Carboxymethylcellulose Gel. AB - PURPOSE: To evaluate macro and microscopically the adhesions developed after using the anti-adherence compound sodium hyaluronate and carboxymethylcellulose (SH-CBMC) gel and to determine the volume of the adhesions using a stereological estimation. METHODS: The study was experimental, random, comparative, and prospective. The subjects of the study were male Wistar rats divided in three groups (n = 10). Group I (control) included rats with no peritoneal injury. Group II rats had a 2 cm diameter injury created bilaterally in the parietal peritoneum at 3 cm from the abdominal midline with electrocautery coated with physiological solution. Group III rats were given the same injuries and coated with SH-CBMC gel. All groups were followed up postoperatively for 30 days, after which a laparotomy was performed to macroscopically determine the presence and type of adhesions. Experimental models were euthanized with anesthetic overdose and biopsies were taken for histopathological examination and stereological estimate of the volume of adhesions. RESULTS: Macroscopic adhesions were 20% less prevalent in Group III compared to Group II, which presented 40% more multiple and firm adhesions, unlike in Group III, in which they were unique and lax. There was a statistically significant decrease in the presence and number of adhesions in rats treated with SH-CBMC gel. Inflammatory infiltrate was significantly lower in rats treated with SH-CBMC gel, but there were no differences in connective tissue, fibrosis, and angiogenesis among groups. There was no statistical difference in the overall volume of adhesions among the treatment groups. CONCLUSIONS: SH-CBMC gel reduces macroscopic presence and number of adhesions and the severity of the inflammatory infiltrate. PMID- 26375455 TI - Effectiveness and Safety of Oral Propranolol versus Other Treatments for Infantile Hemangiomas: A Meta-Analysis. AB - BACKGROUND: Epidemiological studies evaluating treatments for infantile hemangiomas have produced inconsistent results. A meta-analysis of published data was conducted to investigate the effectiveness and safety of oral propranolol versus other treatments for infantile hemangiomas. METHODS: A meta-analysis was conducted based on literature (published from 1960 to December 1, 2014) found on the PubMed, EMBASE, and OVID search engines. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for the outcome measures. Heterogeneity, publication bias and subgroup analysis were performed. RESULTS: A total of 61 studies involving 5,130 participants met the inclusion criteria. Propranolol was found to be a more effective modality in treating IHs (ORs = 0.92; 95%CI, 0.89-0.95) and had fewer complications compared to the other treatments including systemic steroids (ORs = 0.68; 95% CI, 0.59-0.76); laser ablation (ORs = 0.55; 95% CI, 0.43-0.67); other beta-adrenergic blockers (ORs = 0.56; 95% CI, 0.50-0.61) and surgery (ORs = 0.55; 95% CI, 0.28-0.81). A subgroup analysis of propranolol showed that a dose of 2 mg/kg/day or more yielded better outcomes (ORs = 0.92; 95% CI, 0.88-0.95; ORs = 0.95; 95% CI, 0.89-1.00), and IHs that had not been previously treated had better responses to propranolol treatment (ORs = 0.95; 95% CI, 0.91-0.98). CONCLUSIONS: The meta-analysis demonstrated that propranolol was more effective and safer than other therapies in treating IHs. It provides strong evidence for supporting the use of propranolol as a first-line therapy for IHs. PMID- 26375457 TI - Caloric Intake From Fast Food Among Children and Adolescents in the United States, 2011-2012. AB - Consumption of fast food has been linked to weight gain in adults (1). Fast food has also been associated with higher caloric intake and poorer diet quality in children and adolescents (2). From 1994 through 2006, caloric intake from fast food increased from 10% to 13% among children aged 2-18 years (3). This report presents the most recent data on the percentage of calories consumed from fast food among U.S. children by sex, age group, race and Hispanic origin, poverty status, and weight status. PMID- 26375459 TI - The effects of radiation therapy on perfusion of free versus pedicle transverse rectus abdominis myocutaneous (TRAM) flaps in vivo. PMID- 26375458 TI - Solute Carrier Family 26 Member a2 (slc26a2) Regulates Otic Development and Hair Cell Survival in Zebrafish. AB - Hearing loss is one of the most prevalent human birth defects. Genetic factors contribute to the pathogenesis of deafness. It is estimated that one-third of deafness genes have already been identified. The current work is an attempt to find novel genes relevant to hearing loss using guilt-by-profiling and guilt-by association bioinformatics analyses of approximately 80 known non-syndromic hereditary hearing loss (NSHL) genes. Among the 300 newly identified candidate deafness genes, slc26a2 were selected for functional studies in zebrafish. The slc26a2 gene was knocked down using an antisense morpholino (MO), and significant defects were observed in otolith patterns, semicircular canal morphology, and lateral neuromast distributions in morphants. Loss-of-function defects are caused primarily by apoptosis, and morphants are insensitive to sound stimulation and imbalanced swimming behaviours. Morphant defects were found to be partially rescued by co-injection of human SLC26A2 mRNA. All the results suggest that bioinformatics is capable of predicting new deafness genes and this showed slc26a2 is to be a critical otic gene whose dysfunction may induce hearing impairment. PMID- 26375460 TI - Peri-stomal abdominal wall augmentation: Novel use of a pedicled antero-lateral thigh flap. PMID- 26375461 TI - Predicting venous insufficiency in flaps raised on the deep inferior epigastric system using computed tomography (CT) angiography. AB - Computed Tomography Angiogram (CTA) has become a routine part of pre-operative assessment of vascular anatomy and design in perforator flaps. We conducted a retrospective cohort study of flap raised on the deep inferior epigastric system (DIES) at our institution in order to identify CTA signs that might predict venous congestion in these flaps. 98 consecutive patients who had 124 DIES flaps raised from 2008 to 2012 were studied. Of these 124 flaps, four (3.2%) developed venous congestion. Our results showed that a Superficial Inferior Epigastric Vein (SIEV) that is larger than the DIEV at origin is highly predictive of congestion (5.2 vs 3.5 mm, p = 0.007). The findings of an axial non-arborising superficial system (96.7% vs 0, p < 0.001), without connection to deep system perforators (38.1 vs 88.8%, p < 0.001) and a type I pedicle were also predictive (75 vs 64.2%, p = 0.22). These results show the importance of CTAs as a pre-operative study for the identification of risk factors for venous compromise, and their use should prompt a robust discussion of the risk of flap failure with patients, and contingency planning to augment venous drainage with the superficial system if required. PMID- 26375462 TI - Role of Sodium Bicarbonate Cotransporters in Intracellular pH Regulation and Their Regulatory Mechanisms in Human Submandibular Glands. AB - Sodium bicarbonate cotransporters (NBCs) are involved in the pH regulation of salivary glands. However, the roles and regulatory mechanisms among different NBC isotypes have not been rigorously evaluated. We investigated the roles of two different types of NBCs, electroneutral (NBCn1) and electrogenic NBC (NBCe1), with respect to pH regulation and regulatory mechanisms using human submandibular glands (hSMGs) and HSG cells. Intracellular pH (pHi) was measured and the pHi recovery rate from cell acidification induced by an NH4Cl pulse was recorded. Subcellular localization and protein phosphorylation were determined using immunohistochemistry and co-immunoprecipitation techniques. We determined that NBCn1 is expressed on the basolateral side of acinar cells and the apical side of duct cells, while NBCe1 is exclusively expressed on the apical membrane of duct cells. The pHi recovery rate in hSMG acinar cells, which only express NBCn1, was not affected by pre-incubation with 5 MUM PP2, an Src tyrosine kinase inhibitor. However, in HSG cells, which express both NBCe1 and NBCn1, the pHi recovery rate was inhibited by PP2. The apparent difference in regulatory mechanisms for NBCn1 and NBCe1 was evaluated by artificial overexpression of NBCn1 or NBCe1 in HSG cells, which revealed that the pHi recovery rate was only inhibited by PP2 in cells overexpressing NBCe1. Furthermore, only NBCe1 was significantly phosphorylated and translocated by NH4Cl, which was inhibited by PP2. Our results suggest that both NBCn1 and NBCe1 play a role in pHi regulation in hSMG acinar cells, and also that Src kinase does not regulate the activity of NBCn1. PMID- 26375463 TI - Lipidomic Analysis of Chlamydomonas reinhardtii under Nitrogen and Sulfur Deprivation. AB - Chlamydomonas reinhardtii accumulates lipids under complete nutrient starvation conditions while overall growth in biomass stops. In order to better understand biochemical changes under nutrient deprivation that maintain production of algal biomass, we used a lipidomic assay for analyzing the temporal regulation of the composition of complex lipids in C. reinhardtii in response to nitrogen and sulfur deprivation. Using a chip-based nanoelectrospray direct infusion into an ion trap mass spectrometer, we measured a diversity of lipid species reported for C. reinhardtii, including PG phosphatidylglycerols, PI Phosphatidylinositols, MGDG monogalactosyldiacylglycerols, DGDG digalactosyldiacylglycerols, SQDG sulfoquinovosyldiacylglycerols, DGTS homoserine ether lipids and TAG triacylglycerols. Individual lipid species were annotated by matching mass precursors and MS/MS fragmentations to the in-house LipidBlast mass spectral database and MS2Analyzer. Multivariate statistics showed a clear impact on overall lipidomic phenotypes on both the temporal and the nutrition stress level. Homoserine-lipids were found up-regulated at late growth time points and higher cell density, while triacyclglycerols showed opposite regulation of unsaturated and saturated fatty acyl chains under nutritional deprivation. PMID- 26375464 TI - The Effect of Therapeutic HIV Vaccination With ALVAC-HIV With or Without Remune on the Size of the Viral Reservoir (A CTN 173 Substudy). AB - OBJECTIVES: To assess whether therapeutic vaccination with ALVAC-HIV +/- Remune affects viral reservoir size in antiretroviral therapy-treated individuals. METHODS: Participants in CTN 173, a multicentre, randomized, 3-arm, placebo controlled, double-blind study, were vaccinated with ALVAC-HIV +/- Remune (groups 1 and 2, respectively) or with placebos (group 3) over 20 weeks and assessed for changes in the size of their viral reservoirs from weeks 0 to 24. RESULTS: Sixteen participants completed the viral reservoir substudy. The median sizes (interquartile range) of the viral reservoir at baseline (week 0) were 0.07 (0.03 0.37), 0.04 (0.02-0.33), and 0.13 (0.06-0.99) infectious units per million peripheral blood mononuclear cells for groups 1, 2, and 3, respectively; these baseline viral reservoir sizes were not significantly different (P = 0.37). By week 24, the median sizes of the viral reservoirs were 0.04 (0.01-2.16), 0.04 (0.01-0.34), and 0.12 (0.01-0.44) infectious units per million peripheral blood mononuclear cells for groups 1, 2, and 3 respectively; these week 24 viral reservoir sizes were not significantly different (P = 0.91). Furthermore, there were no statistically significant differences between baseline and week 24 reservoir sizes for any of the 3 groups (P = 0.88, P = 1.00, and P = 0.44, respectively). CONCLUSIONS: Despite evidence that ALVAC-HIV +/- Remune was associated with a trend toward a delay in viral rebound and a smaller decrease in CD4 T-cell counts following antiretroviral therapy interruption, ALVAC-HIV +/- Remune did not influence the size of the viral reservoir. PMID- 26375465 TI - Determinants of Weight Evolution Among HIV-Positive Patients Initiating Antiretroviral Treatment in Low-Resource Settings. AB - BACKGROUND: In resource-limited settings, clinical parameters, including body weight changes, are used to monitor clinical response. Therefore, we studied body weight changes in patients on antiretroviral treatment (ART) in different regions of the world. METHODS: Data were extracted from the "International Epidemiologic Databases to Evaluate AIDS," a network of ART programmes that prospectively collects routine clinical data. Adults on ART from the Southern, East, West, and Central African and the Asia-Pacific regions were selected from the database if baseline data on body weight, gender, ART regimen, and CD4 count were available. Body weight change over the first 2 years and the probability of body weight loss in the second year were modeled using linear mixed models and logistic regression, respectively. RESULTS: Data from 205,571 patients were analyzed. Mean adjusted body weight change in the first 12 months was higher in patients started on tenofovir and/or efavirenz; in patients from Central, West, and East Africa, in men, and in patients with a poorer clinical status. In the second year of ART, it was greater in patients initiated on tenofovir and/or nevirapine, and for patients not on stavudine, in women, in Southern Africa and in patients with a better clinical status at initiation. Stavudine in the initial regimen was associated with a lower mean adjusted body weight change and with weight loss in the second treatment year. CONCLUSIONS: Different ART regimens have different effects on body weight change. Body weight loss after 1 year of treatment in patients on stavudine might be associated with lipoatrophy. PMID- 26375466 TI - Use of a Comprehensive HIV Care Cascade for Evaluating HIV Program Performance: Findings From 4 Sub-Saharan African Countries. AB - BACKGROUND: The traditional HIV treatment cascade has been noted to have limitations. A proposed comprehensive HIV care cascade that uses cohort methodology offers additional information as it accounts for all patients. Using data from 4 countries, we compare patient outcomes using both approaches. METHODS: Data from 390,603 HIV-infected adults (>15 years) enrolled at 217 facilities in Kenya, Mozambique, Rwanda, and Tanzania from 2005 to 2011 were included. Outcomes of all patients at 3, 6, and 12 months after enrollment were categorized as optimal, suboptimal, or poor. Optimal outcomes included retention in care, antiretroviral therapy (ART) initiation, and documented transfer. Suboptimal outcomes included retention in care without ART initiation among eligible patients or those without eligibility data. Poor outcomes included loss to follow-up and death. RESULTS: The comprehensive HIV care cascade demonstrated that at 3, 6 and 12 months, 58%, 51%, and 49% of patients had optimal outcomes; 22%, 12%, and 7% had suboptimal outcomes, and 20%, 37% and 44% had poor outcomes. Of all patients enrolled in care, 56% were retained in care at 12 months after enrollment. In comparison, the traditional HIV treatment cascade found 89% of patients enrolled in HIV care were assessed for ART eligibility, of whom 48% were determined to be ART-eligible with 70% initiating ART, and 78% of those initiated on ART retained at 12 months. CONCLUSIONS: The comprehensive HIV care cascade follows outcomes of all patients, including pre-ART patients, who enroll in HIV care over time and uses quality of care parameters for categorizing outcomes. The comprehensive HIV care cascade provides complementary information to that of the traditional HIV treatment cascade and is a valuable tool for monitoring HIV program performance. PMID- 26375467 TI - Cyclosporine A Treatment Inhibits Abcc6-Dependent Cardiac Necrosis and Calcification following Coxsackievirus B3 Infection in Mice. AB - Coxsackievirus type B3 (CVB3) is a cardiotropic enterovirus. Infection causes cardiomyocyte necrosis and myocardial inflammation. The damaged tissue that results is replaced with fibrotic or calcified tissue, which can lead to permanently altered cardiac function. The extent of pathogenesis among individuals exposed to CVB3 is dictated by a combination of host genetics, viral virulence, and the environment. Here, we aimed to identify genes that modulate cardiopathology following CVB3 infection. 129S1 mice infected with CVB3 developed increased cardiac pathology compared to 129X1 substrain mice despite no difference in viral burden. Linkage analysis identified a major locus on chromosome 7 (LOD: 8.307, P<0.0001) that controlled the severity of cardiac calcification and necrosis following infection. Sub-phenotyping and genetic complementation assays identified Abcc6 as the underlying gene. Microarray expression profiling identified genotype-dependent regulation of genes associated with mitochondria. Electron microscopy examination showed elevated deposition of hydroxyapatite-like material in the mitochondrial matrices of infected Abcc6 knockout (Abcc6-/-) mice but not in wildtype littermates. Cyclosporine A (CsA) inhibits mitochondrial permeability transition pore opening by inhibiting cyclophilin D (CypD). Treatment of Abcc6 -/- mice with CsA reduced cardiac necrosis and calcification by more than half. Furthermore, CsA had no effect on the CVB3-induced phenotype of doubly deficient CypD-/-Abcc6-/- mice. Altogether, our work demonstrates that mutations in Abcc6 render mice more susceptible to cardiac calcification following CVB3 infection. Moreover, we implicate CypD in the control of cardiac necrosis and calcification in Abcc6-deficient mice, whereby CypD inhibition is required for cardioprotection. PMID- 26375468 TI - Short-term Efficacy of a Brief Intervention to Reduce Drug Misuse and Increase Drug Treatment Utilization Among Adult Emergency Department Patients. AB - OBJECTIVES: Although brief interventions (BIs) have shown some success for smoking cessation and alcohol misuse, it is not known if they can be applied in the emergency department (ED) to drug use and misuse. The objectives of this investigation were to assess the 3-month efficacy of a BI to reduce drug use and misuse, increase drug treatment services utilization among adult ED patients, and identify subgroups more likely to benefit from the BI. METHODS: This randomized, controlled trial enrolled 18- to 64-year-old English- or Spanish-speaking patients from two urban, academic EDs whose responses to the Alcohol, Smoking, and Substance Involvement Screening Test indicated a need for a brief or intensive intervention. Treatment participants received a tailored BI, while control participants only completed the study questionnaires. At the 3-month follow-up, each participant's past 3-month drug use and misuse and treatment utilization were compared to his or her baseline enrollment data. Regression modeling was used to identify subgroups of patients (per demographic and clinical factors) more likely to stop or reduce their drug use or misuse or engage in drug treatment by the 3-month follow-up assessment. RESULTS: Of the 1,030 participants, the median age was 30 years (interquartile range = 24 to 42 years), and 46% were female; 57% were white/non-Hispanic, 24.9% were black/non-Hispanic, and 15% were Hispanic. The most commonly misused drugs were marijuana, prescription opioids, cocaine/crack, and benzodiazepines. Although at follow-up the proportions of participants reporting any past 3-month drug misuse had decreased in both study arms (control 84% vs. treatment 78%), the decreases were similar between the two study arms (Delta-6.3%; 95% confidence interval [CI] = 13.0% to 0.0). In addition, at follow-up there were no differences between study arms in those who were currently receiving drug treatment (Delta1.8; 95% CI = 3.5 to 6.8), who had received treatment during the past 3 months (Delta-2.0; 95% CI = -6.5 to 2.4), or who at least contacted a treatment program (Delta 1.7; 95% CI = -2.4 to 6.1). Those whose baseline screening indicated the need for a brief instead of a more intensive intervention, and those currently engaged in drug treatment at the 3-month follow-up, were generally more likely to stop or decrease their drug use/misuse. CONCLUSIONS: The BI employed in this study did not reduce drug use and misuse or increase treatment utilization more than the control condition over a 3-month period. Future research should help determine what role, if any, BIs should play in affecting drug use and misuse among ED patients. PMID- 26375469 TI - Chloramphenicol Selection of IS10 Transposition in the cat Promoter Region of Widely Used Cloning Vectors. AB - The widely used pSU8 family of cloning vectors is based on a p15A replicon and a chloramphenicol acetyltransferase (cat) gene conferring chloramphenicol resistance. We frequently observed an increase in the size of plasmids derived from these vectors. Analysis of the bigger molecular species shows that they have an IS10 copy inserted at a specific site between the promoter and the cat open reading frame. Promoter activity from both ends of IS10 has been reported, suggesting that the insertion events could lead to higher CAT production. Insertions were observed in certain constructions containing inserts that could lead to plasmid instability. To test the possibility that IS10 insertions were selected as a response to chloramphenicol selection, we have grown these constructs in the presence of different amounts of antibiotic and we observed that insertions arise promptly under higher chloramphenicol selective pressure. IS10 is present in many E. coli laboratory strains, so the possibility of insertion in constructions involving cat-containing vectors should be taken into account. Using lower chloramphenicol concentrations could solve this problem. PMID- 26375470 TI - Extended Perineal Dermatobia hominis Myiasis in a Traveler Returning From South America. PMID- 26375471 TI - A 12-Week Exercise Program for Pregnant Women with Obesity to Improve Physical Activity Levels: An Open Randomised Preliminary Study. AB - OBJECTIVE: To evaluate whether a 12-week supervised exercise program promotes an active lifestyle throughout pregnancy in pregnant women with obesity. METHODS: In this preliminary randomised trial, pregnant women (body mass index >= 30 kg/m2) were allocated to either standard care or supervised training, from 15 to 27 weeks of gestation. Physical activity was measured by accelerometry at 14, 28 and 36 weeks, while fitness (oxygen consumption (VO2) at the anaerobic threshold), nutrition (caloric intake and macronutrients percentage) and anthropometry were assessed at 14 and 28 weeks of gestation. Analyses were performed using repeated measures ANOVA. RESULTS: A total of fifty (50) women were randomised, 25 in each group. There was no time-group interaction for time spent at moderate and vigorous activity (pinteraction = 0.064), but the exercise group's levels were higher than controls' at all times (pgroup effect = 0.014). A significant time group interaction was found for daily physical activity (p = 0.023); similar at baseline ((22.0 +/- 6.7 vs 21.8 +/- 7.3) x 10(4) counts/day) the exercise group had higher levels than the control group following the intervention ((22.8 +/- 8.3 vs 19.2 +/- 4.5) x 10(4) counts/day, p = 0.020) and at 36 weeks of gestation ((19.2 +/- 1.5 vs 14.9 +/- 1.5) x 10(4) counts/day, p = 0.034). Exercisers also gained less weight than controls during the intervention period despite similar nutritional intakes (difference in weight change = -0.1 kg/week, 95% CI -0.2; 0.02, p = 0.016) and improved cardiorespiratory fitness (difference in fitness change = 8.1%, 95% CI 0.7; 9.5, p = 0.041). CONCLUSIONS: Compared with standard care, a supervised exercise program allows pregnant women with obesity to maintain fitness, limit weight gain and attenuate the decrease in physical activity levels observed in late pregnancy. TRIAL REGISTRATION: ClinicalTrials.gov NCT01610323. PMID- 26375472 TI - The effects of maternal stress and illness during pregnancy on infant temperament: Project Ice Storm. AB - BACKGROUND: To determine whether disaster-related prenatal maternal stress and maternal illness during pregnancy predict maternal-rated temperament status in 6 mo-old infants. METHOD: The temperamental status of 121 infants (60 boys and 61 girls) exposed in utero to varying degrees of maternal stress and/or illness during either first (n = 40), second (n = 43), or third (n = 38) trimester of pregnancy was assessed using the Infant Characteristics Questionnaire. RESULTS: Higher levels of maternal subjective distress and illness were primarily independently associated with poorer temperamental status in the infants. Maternal subjective distress explained 3.4, 3.1, and 9.8% and early pregnancy illness explained 4.3, 5.8, and 2.9% of the variance of the infants' fussy/difficult, dullness, and needs attention temperament dimensions, respectively. CONCLUSION: This is the first study to assess whether temperament status is influenced by disaster-related prenatal maternal stress. Moreover, this is the first study to assess whether maternal stress and illness during pregnancy interact to determine infant temperament status. The findings suggest that while both factors predict temperament status at 6 mo, they do so primarily in an independent manner. These results suggest that pathways through which maternal stress and illness during pregnancy influence temperament status differ. PMID- 26375473 TI - A novel surfactant protein C L55F mutation associated with interstitial lung disease alters subcellular localization of proSP-C in A549 cells. AB - BACKGROUND: Heterozygous mutations of SFTPC, the gene-encoding surfactant protein C (SP-C), result in interstitial lung disease (ILD). However, characterization of mutations located in the mature domain of precursor SP-C (proSP-C) is limited. This study examined the molecular pathogenesis of such a mutation of ILD. METHODS: We employed sequencing of SFTPC and established A549 cells stably expressing several proSP-C mutants. Histopathology and transmission electron microscopy (TEM) of lung tissue from a pediatric patient with ILD were assessed. Effects of mutant proSP-C were evaluated by western blotting, immunofluorescence, and TEM. RESULTS: Sequencing of SFTPC revealed a novel heterozygous mutation, c.163C>T (L55F). In lung tissue, abnormal localization of proSP-C was observed by immunohistochemistry, and small and dense lamellar bodies (LBs) in type II alveolar epithelial cells (AECs) were detected by TEM. TEM of A549 cells stably expressing proSP-C(L55F) displayed abnormal cytoplasmic organelles. ProSP-C(L55F) exhibited a band pattern similar to that of proSP-C(WT) for processed intermediates. Immunofluorescence studies demonstrated that proSP-C(L55F) partially colocalized in CD63-positive cytoplasmic vesicles of A549 cells, which was in contrast to proSP-C(WT). CONCLUSION: We detected a novel c.163C>T mutation located in the mature domain of SFTPC associated with ILD that altered the subcellular localization of proSP-C in A549 cells. PMID- 26375476 TI - Insights into the effect of iron and cobalt doping on the structure of nanosized ZnO. AB - Here we report an in-depth structural characterization of transition metal-doped zinc oxide nanoparticles that have recently been used as anode materials for Li ion batteries. Structural refinement of powder X-ray diffraction (XRD) data allowed the determination of small though reproducible changes in the unit cell dimensions of four ZnO samples (wurtzite structure) prepared with different dopants or different synthesis conditions. Moreover, large variations of the full width at half-maximum of the XRD reflections indicate that the crystallinity of the samples decreases in the order ZnO, Zn0.9Co0.1O, Zn0.9Fe0.1O/C, and Zn0.9Fe0.1O (the crystallite sizes as determined by Williamson-Hall plots are 42, 29, 15, and 13 nm, respectively). X-ray absorption spectroscopy data indicate that Co is divalent, whereas Fe is purely trivalent in Zn0.9Fe0.1O and 95% trivalent (Fe(3+)/(Fe(3+) + Fe(2+)) ratio = 0.95) in Zn0.9Fe0.1O/C. The aliovalent substitution of Fe(3+) for Zn(2+) implies the formation of local defects around Fe(3+) such as cationic vacancies or interstitial oxygen for charge balance. The EXAFS (extended X-ray absorption fine structure) data, besides providing local Fe-O and Co-O bond distances, are consistent with a large amount of charge-compensating defects. The Co-doped sample displays similar EXAFS features to those of pure ZnO, suggesting the absence of a large concentration of defects as found in the Fe-doped samples. These results are of substantial importance for understanding and elucidating the modified electrochemical lithiation mechanism by introducing transition metal dopants into the ZnO structure for the application as lithium-ion anode material. PMID- 26375477 TI - Size-selective recognition by a tubular assembly of phenylene-pyrimidinylene alternated macrocycle through hydrogen-bonding interactions. AB - Study of artificial tubular assemblies as a useful host scaffold for size selective recognition and release of guest molecules is an important subject in host-guest chemistry. We describe well-defined self-assembled nanotubes (NT6mer) formed from pi-conjugated m-phenylene-pyrimidinylene alternated macrocycle 16mer that exhibit size-selective recognition toward a specific aromatic acid. In a series of guest molecules, a size-matched trimesic acid (G3) gives inclusion complexes (NT6mer?G3) in dichloromethane resulting in an enhanced and red-shifted fluorescence. (1)H nuclear magnetic resonance (NMR) titration experiments indicated that the complex was formed in a 1:1 molar ratio. Density functional theory (DFT) calculations and the binding constant value (K = 1.499 * 10(5) M( 1)) of NT6mer with G3 suggested that the complex involved triple hydrogen-bonding interactions. The encapsulated guest G3 molecules can be readily released from the tubular channel through the dissociation of hydrogen bonding by the addition of a polar solvent such as dimethylsulfoxide (DMSO). In contrast, 16mer could not form self-assembled nanotubes in CHCl3 or tetrahydrofuran (THF) solution, leading to weak or no size-selective recognizability, respectively. PMID- 26375474 TI - The role of systemic inflammation linking maternal BMI to neurodevelopment in children. AB - Children of obese mothers are at increased risk of developmental adversities. Maternal obesity is linked to an inflammatory in utero environment, which, in turn, is associated with neurodevelopmental impairments in the offspring. This is an integrated mechanism review of animal and human literature related to the hypothesis that maternal obesity causes maternal and fetal inflammation, and that this inflammation adversely affects the neurodevelopment of children. We propose integrative models in which several aspects of inflammation are considered along the causative pathway linking maternal obesity with neurodevelopmental limitations. PMID- 26375475 TI - Surfactant proteins in pediatric interstitial lung disease. AB - BACKGROUND: Children's interstitial lung diseases (chILD) comprise a broad spectrum of diseases. Besides the genetically defined surfactant dysfunction disorders, most entities pathologically involve the alveolar surfactant region, possibly affecting the surfactant proteins SP-B and SP-C. Therefore, our objective was to determine the value of quantitation of SP-B and SP-C levels in bronchoalveolar lavage fluid (BALF) for the diagnosis of chILD. METHODS: Levels of SP-B and SP-C in BALF from 302 children with chILD and in controls were quantified using western blotting. In a subset, single-nucleotide polymorphisms (SNPs) in the SFTPC promoter were genotyped by direct sequencing. RESULTS: While a lack of dimeric SP-B was found only in the sole subject with hereditary SP-B deficiency, low or absent SP-C was observed not only in surfactant dysfunction disorders but also in patients with other diffuse parenchymal lung diseases pathogenetically related to the alveolar surfactant region. Genetic analysis of the SFTPC promoter showed association of a single SNP with SP-C level. CONCLUSION: SP-B levels may be used for screening for SP-B deficiency, while low SP-C levels may point out diseases caused by mutations in TTF1, SFTPC, ABCA3, and likely in other genes involved in surfactant metabolism that remain to be identified. We conclude that measurement of levels of SP-B and SP-C was useful for the differential diagnosis of chILD, and for the precise molecular diagnosis, sequencing of the genes is necessary. PMID- 26375478 TI - Formaldehyde exposure and its effects during pregnancy: Recommendations for laboratory attendance based on available data. AB - Formalin is commonly used in fixation of cadaveric specimens. Exposure to formaldehyde, a component of formalin and a known carcinogen, during gross anatomy laboratory dissection is a continuing concern for pregnant students and instructors. Since there is little literature on this specific topic, the current review was compiled in the hope of offering recommendations to pregnant students and instructors who are engaged in human anatomical dissection where formalin is used. Relevant articles were obtained through searches of PubMed and Google Scholar for the terms "formaldehyde," "pregnant," "formalin," and "exposure." A literature search was conducted for chemical information and articles about exposure as issued by government regulatory agencies and chemical companies that produce formaldehyde. This led to the compilation of 29 articles each of which included references to previous, relevant, human research. The reviewed literature contains data strongly suggesting that pregnancy can be affected by formaldehyde exposure. Therefore, on the basis our analysis, female students who might be pregnant should avoid formaldehyde exposure, including that in a gross anatomy laboratory. Instructors should find other means of ensuring anatomical competence for these students. PMID- 26375479 TI - From frugivore to folivore: Altitudinal variations in the diet and feeding ecology of the Bioko Island drill (Mandrillus leucophaeus poensis). AB - Variation in the quality and availability of food resources can greatly influence the ecology, behavior, and conservation of wild primates. We studied the influence of altitudinal differences in resource availability on diet in wild drill monkeys (Mandrillus leucophaeus poensis) on Bioko Island, Equatorial Guinea. We compared fecal samples (n = 234) collected across three consecutive dry seasons for drills living in lowland (0-300 m asl) forest with nearby (18 km distance) drills living in montane forest (500-1000 m asl) in the Gran Caldera Southern Highlands Scientific Reserve. Lowland forest drills had a frugivorous diet very similar to that reported from studies on nearby mainland drills (M. l. leucophaeus) and mandrills (M. sphinx), with fruits comprising 90% of their dried fecal samples. However drills living in montane forest had a more folivorous diet, with herbaceous pith, leaves and fungi comprising 74% of their dried fecal samples and fruit becoming a minor component (24%). Furthermore, a dietary preference index indicated that the differences in the proportion of fruit and fibrous vegetation in the diets of lowland compared to montane drills was not simply a result of relative availability. Montane drills were actively consuming a higher mass of the available fruits and fibrous vegetation, a condition reflected in the greater mass of their fresh feces. Our results demonstrate the unexpected flexibility and complexity of dietary choices of this endangered species in two adjacent habitat types, a comparison of considerable importance for many other limited-range species faced with habitat loss and climate change. PMID- 26375481 TI - Reflectance near-infrared measurements for determining changes in skin barrier function and scattering in relation to moisturizer application. AB - Skin moisture relates to the state of multiple skin constituents and aspects, but unfortunately, a device which could provide comprehensive and in vivo analysis is not available. Nevertheless, several reports have demonstrated accurate estimations of dermal water content using near-infrared spectroscopy (NIRS), and the potential of employing this technique in skin analysis. We aim to investigate whether NIRS could detect changes in skin barrier function through evaluation of skin water uptake in relation to moisturizer application. NIR and capacitance data were collected from 20 volunteers at both forearms, prior to and after seven days of regular moisturizer use. Results indicated lower peak intensities at the 1940-nm minima and higher intensities at the 1450-nm equivalent minima with moisturizer abstinence, while the opposite was true with regular moisturizer application. As the light beam would have traveled deeper into the skin at 1450 nm, it has been concluded that long-term, frequent moisturizer use had limited the penetration of extrinsic water. Partial least squares analysis showed that separation of sample's scores increased with abstinence of moisturizer use. Thus, NIRS can provide valuable information not only on dermal water contents but also on additional parameters such as skin barrier function. PMID- 26375482 TI - Synthetic and Immunological Studies of Mycobacterial Lipoarabinomannan Oligosaccharides and Their Protein Conjugates. AB - Lipoarabinomannan (LAM) is one of the major constituents of the Mycobacterium tuberculosis cell wall and an attractive molecular scaffold for antituberculosis drug and vaccine development. In this paper, a convergent strategy was developed for the synthesis of LAM oligosaccharides with an alpha-1,2-linked dimannopyranose cap at the nonreducing end. The strategy was highlighted by efficient coupling of separately prepared nonreducing end and reducing end oligosaccharides. Glycosylations were mainly achieved with thioglycoside donors, which gave excellent yields and stereoselectivity even for reactions between complex oligosaccharides. The strategy was utilized to successfully synthesize tetra-, hepta-, and undecasaccharides of LAM from d-arabinose in 10, 15, and 14 longest linear steps and 7.84, 7.50, and 2.59% overall yields, respectively. The resultant oligosaccharides with a free amino group at their reducing end were effectively conjugated with carrier proteins, including bovine serum albumin and keyhole limpet hemocyanin (KLH), via a bifunctional linker. Preliminary immunological studies on the KLH conjugates revealed that they could elicit robust antibody responses in mice and that the antigen structure had some influence on their immunological property, thus verifying the potential of the oligosaccharides for vaccine development and other immunological studies. PMID- 26375483 TI - Universal Principles in the Repair of Communication Problems. AB - There would be little adaptive value in a complex communication system like human language if there were no ways to detect and correct problems. A systematic comparison of conversation in a broad sample of the world's languages reveals a universal system for the real-time resolution of frequent breakdowns in communication. In a sample of 12 languages of 8 language families of varied typological profiles we find a system of 'other-initiated repair', where the recipient of an unclear message can signal trouble and the sender can repair the original message. We find that this system is frequently used (on average about once per 1.4 minutes in any language), and that it has detailed common properties, contrary to assumptions of radical cultural variation. Unrelated languages share the same three functionally distinct types of repair initiator for signalling problems and use them in the same kinds of contexts. People prefer to choose the type that is the most specific possible, a principle that minimizes cost both for the sender being asked to fix the problem and for the dyad as a social unit. Disruption to the conversation is kept to a minimum, with the two utterance repair sequence being on average no longer that the single utterance which is being fixed. The findings, controlled for historical relationships, situation types and other dependencies, reveal the fundamentally cooperative nature of human communication and offer support for the pragmatic universals hypothesis: while languages may vary in the organization of grammar and meaning, key systems of language use may be largely similar across cultural groups. They also provide a fresh perspective on controversies about the core properties of language, by revealing a common infrastructure for social interaction which may be the universal bedrock upon which linguistic diversity rests. PMID- 26375485 TI - Clinical Research Abstracts of the British Equine Veterinary Association Congress 2015. AB - REASONS FOR PERFORMING STUDY: Rasping of sharp enamel points (SEPs) is the most common procedure performed at routine dental examinations; however, there is little evidence to prove the true clinical significance of SEPs [1]. Maxillary SEPs are thought to cause buccal ulceration and pain on external palpation of the cheeks. Mandibular SEPs are thought to cause lingual ulceration. OBJECTIVES: To examine associations between the presence of SEPs on the cheek teeth rows and the presence of pain on palpation of the cheeks and buccal and/or lingual ulceration. STUDY DESIGN: Retrospective clinical case series. METHODS: Clinical records of routine dental examination performed by 8 veterinary surgeons in a single first opinion practice were examined. Presence of SEPs, buccal and/or lingual ulceration and pain on palpation of the cheeks (externally) were recorded. Chi squared tests were used to examine whether horses exhibiting pain on palpation or oral ulceration were significantly more likely to have SEPs present. RESULTS: Prevalence of buccal SEPs was 84.8% and prevalence of lingual SEPs was 84.3%. Five hundred and forty-eight horses (6.0%) had signs of pain on palpation. Prevalence of buccal ulceration was 5.9%. In contrast, only 0.2% of horses had visible lingual ulceration. Buccal ulceration and pain on palpation were significantly associated with presence of buccal SEPs (P<0.001 for both). Lingual ulceration was not significantly associated with lingual SEPs (P<0.0001). CONCLUSIONS: Buccal SEPs are common and often result in pain and buccal ulceration. Routine rasping would appear to be justified. Lingual SEPs are common but rarely cause lingual ulceration. The value of routine rasping of lingual SEPs is therefore questionable. Ethical animal research: Research ethics committee oversight not currently required by this conference: retrospective study of clinical records. Explicit owner informed consent for inclusion of animals in this study was not stated. SOURCE OF FUNDING: None. Competing interests: None declared. PMID- 26375484 TI - The Role of Protein Excipient in Driving Antibody Responses to Erythropoietin. AB - Human serum albumin (HSA) is an excipient present in formulations of several recombinant protein products that are approved for clinical use. We investigated the relative contributions of HSA and HSA particles to the generation of antibody responses against recombinant human erythropoietin (rhEPO) and the excipient HSA itself. Protein samples were characterized before injection for quantities of monomeric proteins, soluble protein aggregates, and nano- and micron-sized particles. rhEPO, containing various concentrations of HSA particles, were injected three times a week for 8 weeks into mice. Hematocrits and the production of anti-rhEPO and anti-HSA antibodies were determined at various time points. Levels of antibodies against rhEPO in mice injected with HSA-containing rhEPO were higher than those in mice treated with HSA-free rhEPO. Mice injected with formulations that contained particles of HSA produced strong anti-HSA antibody responses; whereas these responses were greatly reduced when particle-free formulations were administered. In contrast, anti-rhEPO antibody responses were not affected by the presence of particles. PMID- 26375486 TI - Functional Characterization of Sirtuin-like Protein in Mycobacterium smegmatis. AB - Nicotinamide adenine dinucleotide (NAD)-dependent deacetylases (sirtuins) are well conserved from prokaryotes to eukaryotes. Functions and regulations of mammalian sirtuins have been extensively studied and indicate that sirtuins play an important role in regulation of biological processes, whereas functions of mycobacterial sirtuins were less explored. To examine functions of the sirtuin like protein in mycobacteria, a Mycobacterium smegmatis sirtuin, MSMEG_5175, was overexpressed in a M. smegmatis strain mc(2)155 to generate an MSMEG_5175 overexpression strain (mc(2)155-MS5175) in the present study. The physiological aspects of mc(2)155-MS5175 strain were characterized showing that they had a lower intracellular NAD level and a higher resistance to isoniazid (INH) as compared to mc(2)155 containing empty pMV261 plasmid (mc(2)155-pMV261). Quantitative proteomic analysis was carried out to determine differentially expressed proteins between mc(2)155-pMV261 and mc(2)155-MS5175. Among 3032 identified proteins, overexpression of MSMEG_5175 results in up-regulation of 34 proteins and down-regulation of 72 proteins, which involve in diverse cellular processes including metabolic activation, transcription and translation, antioxidant, and DNA repair. Down-regulation of catalase peroxidase (KatG) expression in both mRNA and protein levels were observed in mc(2)155-MS5175 strain, suggesting that a decrease in cellular NAD content and down-regulation of KatG expression contribute to the higher resistance to INH in mc(2)155-MS5175. Using a combination of immunoprecipitation and proteomic analysis, we found that acetylation in 27 proteins was decreased in mc(2)155-MS5175 as compared to those in mc(2)155-pMV261, suggesting that these proteins including the beta prime subunit of RNA polymerase (rpoC), ribosomal proteins, and metabolic enzymes were substrates of MSMEG_5175. Acetylation changes in rpoC may affect its function and cause changes in global gene transcription. Taken together, these results suggest that MSMEG_5175 regulates diverse cellular processes resulting in an increase in INH resistance in mycobacteria, and provide a useful resource to further biological exploration into functions of protein acetylation in mycobacteria. PMID- 26375487 TI - Clinical Research Abstracts of the British Equine Veterinary Association Congress 2015. AB - REASONS FOR PERFORMING STUDY: Decreased efficacy of veterinary antimicrobials and increased prevalence of multi-drug resistance (MDR) is of concern, but little is known of antimicrobial resistance encompassing the New Zealand (NZ) equine population. Recent concerns have arisen over the emergence of multi-resistant bacteria [1], especially on NZ stud farms where antibiotics are frequently used for respiratory disease without veterinary input [2]. OBJECTIVES: To describe bacterial culture and antimicrobial sensitivity results from respiratory samples submitted of young horses (4 weeks to 3 years old). STUDY DESIGN: Retrospective study of clinical pathology records. METHODS: A database search for isolates and sensitivity of respiratory samples from young horses (April 2004-July 2014) was conducted. The results of in vitro sensitivity testing by Kirby-Bauer disk diffusion were tabulated for major bacterial species isolated. Multiple correspondence analysis was used to describe clustering of multi-drug resistance (MDR) and selected demographic variables. RESULTS: 237/289 eligible respiratory samples had at least one aerobic bacterial isolate. Most of the 774 bacterial isolates were Gram-positive (68%). Streptococcus species were the most common genus isolated (40% of isolates). Sensitivity of Streptococcus spp. to penicillin, gentamicin and ceftiofur was >85%, but only 53% to trimethoprim sulfamethoxone. Gram-negative sensitivity to ceftiofur, tetracycline, and trimethoprim-sulfamethoxone was <75%. MDR was found for 16% of isolates and in 39% of horses. CONCLUSIONS: Penicillin is an appropriate first-line antimicrobial for use in most NZ young horses with suspected bacterial respiratory infection. However, based on findings of MDR, submission of samples for culture and monitoring of sensitivity should be used to inform antimicrobial selection. Ethical animal research: Not applicable. Sources of funding: Massey University McGeorge Fund; New Zealand Equine Research Foundation. Competing interests: None declared. PMID- 26375489 TI - Clinical Research Abstracts of the British Equine Veterinary Association Congress 2015. AB - REASONS FOR PERFORMING STUDY: Diffusion of local anaesthetic solution after a mid pastern ring block has not been investigated. OBJECTIVES: To demonstrate potential distribution of local anaesthetic solution following injection of radiodense contrast medium as performed for a mid-pastern ring block. STUDY DESIGN: Experimental. METHODS: Twelve mature horses were used. One and a half ml radiodense contrast medium was injected over the medial or lateral palmar digital nerve at the level of the proximal aspect of the ungular cartilages. A dorsal ring block was performed on the ipsilateral side, 1.5 cm proximal to the palpable palmar aspect of the proximal eminence of the middle phalanx, using 2 or 5 ml contrast medium. Both forelimbs were injected on 2 days (48 injections). Four standard radiographic views of the pastern were obtained immediately, 10 and 20 min after injections. Images were analysed subjectively and objectively. RESULTS: After dorsal injections the contrast medium was distributed in a diffuse patch over the ipsilateral half of the proximal phalanx (PP), extending proximally over the half of the length of PP in all limbs (greatest proximal extension: 89.0% of the length of PP [from distal] after 2 ml, 94.2% after 5 ml). There was significant proximal diffusion in the first 10 min after injection and significant dorsal diffusion between all time points (P<0.01). There was significant positive association between injected volume and the proximal extension of the dorsal contrast patch (P = 0.01). The median dorsal diffusion was to the dorsal midline of PP; 5 ml contrast medium resulted in significantly greater dorsal diffusion than 2 ml (P<0.01). The dorsal and the palmar contrast patches did not merge. CONCLUSIONS: Diffusion to the proximal aspect of P1 occurred even after injection of only 2 ml contrast medium. Fetlock region pain may be influenced by a mid-pastern ring block. Ethical animal research: Written consent had been obtained from a representative of the horses' owner prior to starting the study. SOURCE OF FUNDING: None. Competing interests: None declared. PMID- 26375488 TI - Golgi Associated HIF1a Serves as a Reserve in Melanoma Cells. AB - Hypoxia-inducible factor-1alpha (HIF1a) is a key transcriptional regulator that enables cellular metabolic adaptation to low levels of oxygen. Multiple mechanisms, including lysosomal degradation, control the levels of HIF1a protein. Here we show that HIF1a protein degradation is resistant to lysosomal inhibition and that HIF1a is associated with the Golgi compartment in melanoma cells. Although pharmacological inhibitors of prolyl hydroxylation, neddylation and the proteasome inhibited degradation of HIF1a, attenuation of lysosomal activity with chloroquine did not alter the levels of HIF1a or its association with Golgi. Pharmacological disruption of Golgi resulted in nuclear accumulation of HIF1a. However, blockade of ER-Golgi protein transport in hypoxia reduced the transcript levels of HIF1a target genes. These findings suggest a possible role for the oxygen-dependent protein folding process from the ER-Golgi compartment in fine tuning HIF1a transcriptional output. PMID- 26375490 TI - Effect of Processed Onions on the Plasma Concentration of Quercetin in Rats and Humans. AB - Onion is a major dietary source of the bioactive flavonoid, quercetin. Quercetin aglycone (QA) is exclusively distributed in the onion peel, although quercetin-4' beta-O-glucoside (Q4'G) is present in both the peel and the bulb, and quercetin 3,4'-beta-O-diglucoside (Q3,4'diG) is present only the bulb. The bioavailability of flavonoids from fruits and vegetables is frequently affected by the manufacturing process and related conditions. The present study aimed to estimate the effect of food processing on the bioavailability of onion QA and its glucosides, Q4'G and Q3,4'diG, provided through the consumption of onion products. Rats were fed onion peel and onion bulb products-mixed meal or pure QA/Q4'G+Q3,4'diG-mixed meal at 5 mg QA equivalent/kg body weight. A comparison of the blood plasma concentrations strongly suggested that quercetin glucosides (Q4'G and Q3,4'diG) are superior or at least equal to QA in their bioavailability, when each purified compound is mixed with the meal. The intake of a peel powder-containing meal provided a significantly higher increase of plasma quercetin concentration than the peel extract, bulb powder, bulb extract, and bulb saute containing meals at each period tested. A human ingestion study confirmed the superiority of onion peel powder to onion peel extract. The difference of log P for QA between peel powder and peel extract indicated that a food matrix improves the bioavailability of QA in onion peel products. These results demonstrated that the bioavailability of quercetin provided by not the onion bulb but the onion peel is significantly affected by food processing. PRACTICAL APPLICATION: Onion is a popular source of antioxidative flavonoid quercetin and its vascular function attracts considerable attention in relation to anti-atherosclerotic effect. The present study estimated the effect of food processing on the bioavailability of onion quercetin aglycone and its glucosides provided through the consumption of onion products. The intake of a peel powder containing meal showed a significantly higher bioavailability than the peel extract, bulb powder, bulb extract, and bulb saute containing meals. Hence, food processing of onion peel may enhance the health impact of onion quercetin by elevating its bioavailability. PMID- 26375491 TI - Choosing Wisely((r)): Things we do for no reason. PMID- 26375492 TI - A hybrid model for automatic identification of risk factors for heart disease. AB - Coronary artery disease (CAD) is the leading cause of death in both the UK and worldwide. The detection of related risk factors and tracking their progress over time is of great importance for early prevention and treatment of CAD. This paper describes an information extraction system that was developed to automatically identify risk factors for heart disease in medical records while the authors participated in the 2014 i2b2/UTHealth NLP Challenge. Our approaches rely on several nature language processing (NLP) techniques such as machine learning, rule-based methods, and dictionary-based keyword spotting to cope with complicated clinical contexts inherent in a wide variety of risk factors. Our system achieved encouraging performance on the challenge test data with an overall micro-averaged F-measure of 0.915, which was competitive to the best system (F-measure of 0.927) of this challenge task. PMID- 26375493 TI - Comparison of UMLS terminologies to identify risk of heart disease using clinical notes. AB - The second track of the 2014 i2b2 challenge asked participants to automatically identify risk factors for heart disease among diabetic patients using natural language processing techniques for clinical notes. This paper describes a rule based system developed using a combination of regular expressions, concepts from the Unified Medical Language System (UMLS), and freely-available resources from the community. With a performance (F1=90.7) that is significantly higher than the median (F1=87.20) and close to the top performing system (F1=92.8), it was the best rule-based system of all the submissions in the challenge. We also used this system to evaluate the utility of different terminologies in the UMLS towards the challenge task. Of the 155 terminologies in the UMLS, 129 (76.78%) have no representation in the corpus. The Consumer Health Vocabulary had very good coverage of relevant concepts and was the most useful terminology for the challenge task. While segmenting notes into sections and lists has a significant impact on the performance, identifying negations and experiencer of the medical event results in negligible gain. PMID- 26375495 TI - Discrete dynamics of contagious social diseases: Example of obesity. AB - Modeling contagious diseases needs to incorporate information about social networks through which the disease spreads as well as data about demographic and genetic changes in the susceptible population. In this paper, we propose a theoretical framework (conceptualization and formalization) which seeks to model obesity as a process of transformation of one's own body determined by individual (physical and psychological), inter-individual (relational, i.e., relative to the relationship between the individual and others) and socio-cultural (environmental, i.e., relative to the relationship between the individual and his milieu) factors. Individual and inter-individual factors are tied to each other in a socio-cultural context whose impact is notably related to the visibility of anybody being exposed on the public stage in a non-contingent way. The question we are dealing with in this article is whether such kind of social diseases, i.e., depending upon socio-environmental exposure, can be considered as "contagious". In other words, can obesity be propagated from individual to individual or from environmental sources throughout an entire population? PMID- 26375494 TI - Ceftriaxone attenuates acute cocaine-evoked dopaminergic neurotransmission in the nucleus accumbens of the rat. AB - BACKGROUND AND PURPOSE: Ceftriaxone is a beta-lactam antibiotic and glutamate transporter activator that reduces the reinforcing effects of psychostimulants. Ceftriaxone also reduces locomotor activation following acute psychostimulant exposure, suggesting that alterations in dopamine transmission in the nucleus accumbens contribute to its mechanism of action. In the present studies we tested the hypothesis that pretreatment with ceftriaxone disrupts acute cocaine-evoked dopaminergic neurotransmission in the nucleus accumbens. EXPERIMENTAL APPROACH: Adult male Sprague-Dawley rats were pretreated with saline or ceftriaxone (200 mg kg(-1) , i.p. * 10 days) and then challenged with cocaine (15 mg kg(-1) , i.p.). Motor activity, dopamine efflux (via in vivo microdialysis) and protein levels of tyrosine hydroxylase (TH), the dopamine transporter and organic cation transporter as well as alpha-synuclein, Akt and GSK3beta were analysed in the nucleus accumbens. KEY RESULTS: Ceftriaxone-pretreated rats challenged with cocaine displayed reduced locomotor activity and accumbal dopamine efflux compared with saline-pretreated controls challenged with cocaine. The reduction in cocaine-evoked dopamine levels was not counteracted by excitatory amino acid transporter 2 blockade in the nucleus accumbens. Pretreatment with ceftriaxone increased Akt/GSK3beta signalling in the nucleus accumbens and reduced levels of dopamine transporter, TH and phosphorylated alpha-synuclein, indicating that ceftriaxone affects numerous proteins involved in dopaminergic transmission. CONCLUSIONS AND IMPLICATIONS: These results are the first evidence that ceftriaxone affects cocaine-evoked dopaminergic transmission, in addition to its well-described effects on glutamate, and suggest that its ability to attenuate cocaine-induced behaviours, such as psychomotor activity, is due in part to reduced dopaminergic neurotransmission in the nucleus accumbens. PMID- 26375496 TI - Bioaerosol exposure to personnel in a clinical environment absent patients. AB - Nosocomial infections pose a significant and escalating threat to both patients and healthcare workers (HCWs). By their nature, hospitals induce antibiotic resistance in virulent and commensal strains, leading to increasingly severe hospital-acquired infections. This study measured environmental exposure experienced by domestic staff cleaning vacated patient rooms of a community hospital to bacteria in ambient bioaerosols. While they cleaned the room, participants wore an N95 filtering facepiece respirator (FFR), from which coupons were cut and bacteria were extracted, cultured and enumerated. Extrapolation to the full area of the respirator yielded measured exposures of 0.2-1.4 * 10(4) colony-forming units/hour, of which ~97% collected on the front layer of the N95, suggesting a possible role for minimal respiratory protection in nonpatient environments. Random resistance testing of 1.6% of the isolates showed that ~70% of both Gram-positive and Gram-negative organisms exhibited resistance to oxacillin and ~9% of the Gram-positives displayed resistance to vancomycin. These data provide an estimate for mask bioaerosol loading that can be used in risk modeling and to refine strategies for reuse of FFRs during critical shortages. PMID- 26375497 TI - Inflammation, Endothelial Dysfunction, and Thromboembolism. PMID- 26375498 TI - Endometrial Stromal Sarcoma with Intravenous and Cardiac Extension. PMID- 26375499 TI - High Intensity Interval versus Moderate Intensity Continuous Training in Patients with Coronary Artery Disease: A Meta-analysis of Physiological and Clinical Parameters. AB - INTRODUCTION: Exercise-based cardiac rehabilitation for patients with coronary artery disease (CAD) significantly improves their outcome, although the optimal mode of exercise training remains undetermined. Previous analyses have been constrained by small sample sizes and a limited focus on clinical parameters. Further, results from previous studies have been contradicted by a recently published large RCT. METHOD: We performed a meta-analysis of published randomised controlled trials to compare high intensity interval training (HIIT) and moderate intensity continuous training (MCT) in their ability to improve patients' aerobic exercise capacity (VO2peak) and various cardiovascular risk factors. We included patients with established coronary artery disease without or without impaired ejection fraction. RESULTS: Ten studies with 472 patients were included for analyses (218 HIIT, 254 MCT). Overall, HIIT was associated with a more pronounced incremental gain in participants' mean VO2peak when compared with MCT (+1.78mL/kg/min, 95% CI: 0.45-3.11). Moderate intensity continuous training however was associated with a more marked decline in patients' mean resting heart rate (-1.8/min, 95% CI: 0.71-2.89) and body weight (-0.48kg, 95% CI: 0.15-0.81). No significant differences were noted in the level of glucose, triglyceride and HDL at the end of exercise program between the two groups. CONCLUSION: High intensity interval training improves the mean VO2peak in patients with CAD more than MCT, although MCT was associated with a more pronounced numerical decline in patients' resting heart rate and body weight. The underlying mechanisms and clinical relevance of these results are uncertain, and remain a potential focus for future studies. PMID- 26375500 TI - When is 'Urgent' Really Urgent and Does it Matter? Misclassification of Procedural Status and Implications for Risk Assessment in Cardiac Surgery. AB - BACKGROUND: Many patients classified as "urgent" in Australia New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) registry contradict the prescribed definition (surgery within 72hours of angiogram or unplanned admission). The aim was to examine the impacts of this misclassification on the prediction of 30-day mortality following cardiac surgery. METHODS: The 'reported clinical status' was compared with a 'corrected clinical status' following reclassification based on the standard definition calculated from raw data. Observed-to-predicted risk ratios (OPRs) of 30-day mortality were calculated for the model using reported status and corrected status and compared. A Bland-Altman plot was generated to examine the level of agreement between the two OPRs. RESULTS: Of 18496 cases reported as urgent, 49.9% were operated after 72hours, leading to misclassification of 14.6% in the registry. Misclassified patients had significantly higher mortality (3.5%) than true urgent patients (2.9%). Underweight (OR:1.6,CI:1.2-2.1), dialysis (OR:1.4,CI:1.1-1.7), endocarditis (OR:2.1,CI:1.7-2.5), shock (OR:1.6,CI:1.3-2.0) and poor ejection fraction (OR:1.2,CI:1.1-1.4) were significant predictors of misclassification. Bland- Altman plot demonstrates significant disagreement between two risk estimates (P<0.001). Misclassification results in overestimation of risk by 9.1%. Observed to-predicted risk increased with corrected definition (0.8975 vs 0.9875), suggesting poorer calibration with reported status. CONCLUSIONS: In the ANZSCTS database, misclassification prevalence is 14.6%. Misclassification compromises the discrimination capacity and calibration of the model and results in overestimation of mortality risk. PMID- 26375502 TI - Clinical Research Abstracts of the British Equine Veterinary Association Congress 2015. PMID- 26375501 TI - Non-adherent culture induces paclitaxel resistance in H460 lung cancer cells via ERK-mediated up-regulation of betaIVa-tubulin. AB - Circulating tumor cells (CTCs) are metastasizing epithelial cancer cells that adapt to survive when floating in bloodstream during metastasis. This condition can be mimicked in vitro by using non-adherent cell culture. The chemosensitivity of CTCs appears to correlate with the response of metastatic cancer patients to therapy, but chemoresistance is also frequently observed in advanced stage cancer patients, who have never previously received chemotherapy. We hypothesize that adaptation of epithelial cancer cells to become floating CTCs could lead to development of chemoresistance. Here, we explore whether chemoresistance is induced in epithelial cancer cells when cultured under non-adherent conditions. Increased paclitaxel-specific resistance was observed in floating cells compared to attached cells in H460, MCF-7, and HepG2 human cancer cell lines, by 15.6-, 3.9-, and 2.6-fold increases in IC50 values, respectively. qRT-PCR analysis showed that a paclitaxel-resistant beta-tubulin isotype, betaIVa-tubulin, was the most up-regulated gene compared with other beta-tubulin isotypes in H460 floating cells, concomitant with elevated ERK activation. ERK inhibitor treatment could attenuate the up-regulation of betaIVa-tubulin, and decreased the paclitaxel resistance of H460 floating cells, even though other beta-tubulin isotypes were up-regulated when the ERK activation was blocked. In conclusion, we show induction of paclitaxel resistance in epithelial cancer cells, when floating in non-adherent culture, and this might occur with CTCs of cancer patients. PMID- 26375503 TI - A simplified cuff technique for abdominal aortic transplantation in mice. AB - BACKGROUND: Allograft arteriopathy is still a leading cause of late organ failure. The aortic allograft model in mice has been used to study chronic rejection and has given useful information in the development of graft arteriosclerosis. However, the technical difficulties of small vessel anastomoses still continue to limit its widespread use. We introduce a new simple method for aortic transplantation in mice. METHODS: The descending aorta or infrarenal aorta from the donor mouse was anastomosed to the infrarenal aorta using a cuff technique. Aortic transplantation was performed in 30 mice, 10 isografts and 20 allografts. No immunosuppression was administered, and the recipients were sacrificed at day 28. The grafts were histologically analyzed. RESULTS: Implantation of grafts could be completed in an average of 23 min. There was no technical failure in all 60 anastomoses. The overall survival rate was 93.3%. Histology of aortas revealed typical aspects of chronic rejection in the allografts at day 28. No significant lesion was observed in isografts. CONCLUSIONS: We have developed an innovative, stable, and simple aortic transplantation model in mice, which is useful for vascular research in transplantation and beyond. PMID- 26375504 TI - The fate of human platelets exposed to porcine renal endothelium: a single-pass model of platelet uptake in domestic and genetically modified porcine organs. AB - BACKGROUND: Thrombocytopenia may represent a significant challenge to the clinical application of solid-organ xenotransplantation. When studied in a pig-to primate model, consumptive coagulopathy has challenged renal xenografts. New strategies of genetic manipulation have altered porcine carbohydrate profiles to significantly reduce human antibody binding to pig cells. As this process continues to eliminate immunologic barriers to clinical xenotransplantation, the relationship between human platelets and pig organs must be considered. METHODS: Genetically modified pigs that were created by the CRISPR/Cas9 system with alpha 1,3-galactosyltransferase (GGTA1)(-/-) or GGTA1(-/-) cytidine monophosphate-N acetylneuraminic acid hydroxylase(-/-) phenotype, as well as domestic pigs, were used in this study. Autologous porcine platelets were isolated from donor animal blood collection, and human platelets were obtained from a blood bank. Platelets were fluorescently labeled and in a single-pass model, human, or autologous platelets were perfused through porcine organs at a constant concentration and controlled temperature. Platelet uptake was measured by sampling venous output and measuring sample florescence against input florescence. In vitro study of the interaction between human platelets and porcine endothelial cells was accomplished by immunohistochemical stain and confocal microscopy. RESULTS: Differences between human and autologous platelet loss through the porcine kidney were not significant in any genetic background tested (WT P = 0.15, GGTA1(-/-)P = 0.12, GGTA1(-/-) cytidine monophosphate-N-acetylneuraminic acid hydroxylase(-/-)P = 0.25). The unmodified porcine liver consumed human platelets in a single-pass model of platelet perfusion in fewer than 10 min. WT suprahepatic inferior vena cava fluoresce reached a maximum of 76% of input fluoresce within the human platelet cohort and was significantly lower than the autologous platelet control cohort (P = 0.001). Confocal microscopic analysis did not demonstrate a significant association between human platelets and porcine renal endothelial cells compared with porcine liver endothelial positive controls. CONCLUSIONS: Our results suggest that in the absence of immunologic injury, human platelets respond in a variable fashion to organ-specific porcine endothelial surfaces. Human platelets are not removed from circulation by exposure to porcine renal endothelium but are removed by unmodified porcine hepatic endothelium. Kidneys possessing genetic modifications currently relevant to clinical xenotransplantation failed to consume human platelets in an isolated single-pass model. Human platelets did not exhibit significant binding to renal endothelial cells by in vitro assay. PMID- 26375505 TI - Astragaloside IV protects against polymicrobial sepsis through inhibiting inflammatory response and apoptosis of lymphocytes. AB - BACKGROUND: Sepsis is a major clinical challenge in modern medicine, representing one of the leading causes of death in developed countries. The syndrome is a consequence of a dysregulated immune response, including early uncontrolled systemic inflammation and prolonged immunosuppression in the late phase. The present study was conducted to investigate the therapeutic effects of astragaloside IV (ASI-IV) on the cecal ligation and puncture (CLP)-induced sepsis in mice. MATERIALS AND METHODS: C57BL/6 mice were randomly divided into sham control + vehicle, CLP + vehicle, and CLP + ASI-IV groups. ASI-IV (3 mg/kg) was intravenously injected 1 h after CLP surgery. Survival rate, bacterial clearance, inflammatory mediators, phagocytes emigration, histopathology, and lymphocyte apoptosis were examined. The effects of ASI-IV on peritoneal macrophage activation and its underlying mechanisms were also evaluated. RESULTS: We reported that treatment with ASI-IV significantly improved survival in septic mice. In agreement with this protective effect, the pathologic damage that was typically seen in lung and spleen was ameliorated; the level of bacterial burden was lessened; inflammatory cytokines and chemokines in circulation were profoundly reduced; lymphocyte apoptosis was inhibited. ASI-IV suppressed LPS induced macrophage activation through inhibiting NF-kappaB and ERK1/2 signaling pathways. CONCLUSIONS: ASI-IV protected mice against polymicrobial sepsis by inhibiting inflammatory response and lymphocyte apoptosis. Therefore, ASI-IV might provide a novel therapeutic approach for septic patients. PMID- 26375506 TI - Hepatitis B Virus Seroprevalence Among Children With Cancer in Sudan. AB - BACKGROUND: The seroprevalence of hepatitis B among children with cancer in Sudan is unknown. The aim of this study was to detect the seroprevalence of hepatitis B virus (HBV) infection in children with malignancy and its correlation with different risk factors. PROCEDURE: This study included 178 children with malignancy presenting to the Radioisotope Center in Khartoum during the period of May-July 2011. Sixty-four healthy children served as controls. Sera from patients and controls were investigated for HBV total anti-core antibody, HBV surface antigen (HBsAg), and HBV e antigen (HBeAg). RESULTS: HBV total anti-core antibody was positive in 71/178 (39.9%), HBsAg was positive in 38 (21.3%), and HBeAg was positive in 19 (10.7%). Blood product transfusion, surgical exposure, chemotherapy, malignancy type, and sex did not affect the seroprevalence of HBV in this study. Vaccinated children had reduced rates of exposure compared to non vaccinated patients. CONCLUSION: There is a high seroprevalence of HBV in children with malignancies in Sudan. Vaccination appears to play a major protective role. PMID- 26375507 TI - Molecular dynamics simulation of doxorubicin adsorption on a bundle of functionalized CNT. AB - In this study, molecular dynamics simulation is used to investigate the adsorption of an anticancer drug, doxorubicin, on bundles of functionalized single-walled carbon nanotubes (SWNTs) in an aqueous solution. Carboxylic group has been selected as the functional group. Molecular dynamics (MD) simulations are performed for both separated systems containing a SWNT bundle and a functionalized carbon nanotube bundle, and results are compared with existing experimental data. MD results show that doxorubicin can be adsorbed on CNTs using different methods such as entrapment within CNT bundle, attachment to the side wall of the CNT, and adsorption on the CNT inner cavity. For functionalized CNT, the adsorption of drugs on the functional groups is essential for predicting the enhancement of drug loading on the functionalized nanotubes. Furthermore, the adsorption behavior of doxorubicin on CNTs is fitted with Langmuir and Freundlich isotherm models. The results show that Langmuir model can predict the adsorption behavior of doxorubicin on CNTs more accurately than Freundlich model does. As predicted by this isotherm model, the adsorption process of doxorubicin on CNTs is relatively difficult, but it can be improved by increasing the functional groups on the CNTs surface. PMID- 26375508 TI - The use of intravesical hyaluronic acid for recurrent urinary tract infections in children: a case-series study. AB - BACKGROUND: This is the first study performed to evaluate the effects of intravesical hyaluronic acid (IHA) instillation on diminishing the frequency of recurrent urinary tract infections (UTIs) in children. METHODS: Fifteen children (10 girls, 5 boys) with recurrent UTIs were divided into two groups as either complicated (group 1) (with accompanying disorders including vesicoureteral reflux or neurogenic bladder) or uncomplicated patients (group 2). After administration of weekly four sessions of IHA therapy the patients were followed up monthly for 2 years and classified as responsive (complete/partial) or unresponsive to treatment. RESULTS: 53.3% of the patients with recurrent UTIs were complicated. In group 1 (n = 8), complete and partial response rates were 62.5% (n = 5) and 25% (n = 2), respectively. There was no response in 12.5% (n = 1) of the cases in group 1. In group 2 (n = 7), complete and partial response rates were 71.4% (n = 5) and 14.3% (n = 1), respectively. In this group, 14.3% (n = 1) of the patients were found to be unresponsive to IHA treatment. No side effects were observed in any of the patients. CONCLUSIONS: IHA administration is considered as an effective treatment modality which significantly reduces the prevalence of or even provides complete recovery from recurrent UTIs in childhood. Therefore, it is believed that this approach can be used as a promising alternative to widespread use of antibiotics in this patient group. PMID- 26375509 TI - Evidence accumulation as a model for lexical selection. AB - We propose and demonstrate evidence accumulation as a plausible theoretical and/or empirical model for the lexical selection process of lexical retrieval. A number of current psycholinguistic theories consider lexical selection as a process related to selecting a lexical target from a number of alternatives, which each have varying activations (or signal supports), that are largely resultant of an initial stimulus recognition. We thoroughly present a case for how such a process may be theoretically explained by the evidence accumulation paradigm, and we demonstrate how this paradigm can be directly related or combined with conventional psycholinguistic theory and their simulatory instantiations (generally, neural network models). Then with a demonstrative application on a large new real data set, we establish how the empirical evidence accumulation approach is able to provide parameter results that are informative to leading psycholinguistic theory, and that motivate future theoretical development. PMID- 26375510 TI - Comparative transcriptome analysis of atrial septal defect identifies dysregulated genes during heart septum morphogenesis. AB - Congenital heart disease (CHD) is one of most common birth defects, causing fetal loss and death in newborn all over the world. Atrial and ventricular septal defects were the most common CHD subtypes in most districts. During the past decades, several genes were identified to control atrial septum formation, and mutations of these genes can cause cardiac septation defects. However, the pathogenic mechanism of ASD on transcriptional levels has not been well elucidated yet. Herein, we performed comparative transcriptome analysis between normal and atrial septal defect (ASD) patients by Illumina RNA sequencing (RNA seq). Advanced bioinformatic analyses were employed to identify dysregulated genes in ASD. The results indicated that cardiac specific transcriptional factors (GATA4 and NKX2-5), extracellular signal molecules (VEGFA and BMP10) and cardiac sarcomeric proteins (MYL2, MYL3, MYH7, TNNT1 and TNNT3) were downregulated in ASD which may affect heart atrial septum formation, cardiomyocyte proliferation and cardiac muscle development. Importantly, cell cycle was dominant pathway among downregulated genes, and decreased expression of the proteins included in cell cycle may disturb cardiomyocyte growth and differentiation during atrial septum formation. Our study provided evidences of understanding pathogenic mechanism of ASD and resource for validation of CHD genomic studies. PMID- 26375511 TI - Microtubule dynamics and tumor invasion involving MCAK. PMID- 26375512 TI - Rituximab treatment for relapsed opsoclonus-myoclonus syndrome. AB - INTRODUCTION: Opsoclonus-myoclonus syndrome (OMS) is a rare neurological disorder that is associated with paraneoplastic diseases. Because OMS can frequently relapse, patients may be inflicted with neurological problems for a long time. Recently, rituximab (RTX) was introduced as a drug to treat OMS. To assess RTX treatment, we studied a patient who experienced recurrence of OMS. CASE REPORT: A 2-year-old Japanese boy, who had left adrenal neuroblastoma, suddenly showed OMS symptoms, including ataxia and opsoclonus. Surgical resection of the tumor and subsequent steroid therapy ameliorated his symptoms. When OMS relapsed during the time when prednisolone was reduced, he was treated with full-dose RTX therapy (375 mg/m2/week) for 4 consecutive weeks. However, 1year later, he presented again with OMS symptoms. This time, we only administered an additional single dose of RTX treatment (375 mg/m2), allowing remission of OMS symptoms. During 2 years after the additional RTX treatment, OMS symptoms did not appear, even when prednisolone was reduced. He had no adverse events associated with RTX during the whole treatment period. CONCLUSIONS: An additional single-dose RTX therapy might be effective for relapsed OMS patients who were previously treated with full-dose RTX therapy. PMID- 26375513 TI - Alcohol craving and demand mediate the relation between posttraumatic stress symptoms and alcohol-related consequences. AB - Posttraumatic stress (PTS) symptoms are associated with alcohol-related consequences, but there is a need to understand mediators that may help explain the reasons for this relationship. Individuals with PTS may experience elevated craving and alcohol reward value (demand), which may contribute to risk for alcohol-related consequences. We examined relationships between PTS status, craving, alcohol demand, and alcohol-related consequences in PTS-positive (n = 64) and PTS-negative (n = 200) college students (M age = 21.7; 77% women; 54% Caucasian; 34% African American) who endorsed past-month alcohol use. We tested craving and alcohol demand as mediators of the relation between PTS status and alcohol-related consequences. Craving (B = .04, SE = .02, 95% CI [.01, .10]), demand intensity (B = .02, SE = .02, 95% CI [.001, .07]), and demand elasticity (B = .05, SE = .03, 95% CI [.006, .12]) significantly mediated the association between PTS symptoms and alcohol-related consequences. Craving remained a significant mediator in a multiple mediators model (B = .08, SE = .04, 95% CI [.03, .19]). Craving and alcohol demand may partially explain the relation between PTS status and alcohol-related consequences. Craving may be especially salient for individuals with PTS symptoms, as it may lead to more severe alcohol related consequences even in the absence of elevated alcohol consumption. PMID- 26375514 TI - Interaction effect of contingency management and sex on delay-discounting changes among treatment-seeking smokers. AB - Despite the potential influence of sex on delay-discounting rates, there is no previous evidence with regard to the effect of this variable on the clinical interventions aimed at modifying delay-discounting rates. This study assessed the effect of sex on the association between the type of treatment received (either cognitive-behavioral treatment [CBT] alone or combined with contingency management [CM + CBT]) and delay-discounting changes at end of treatment and 6 month follow-up. This aim was addressed after controlling for the influence of baseline delay discounting. Treatment-seeking smokers (N = 116) were randomly assigned to either CM + CBT (n = 69) or CBT alone (n = 47). Participants completed delay-discounting assessments at intake, at end of treatment, and at 6 month follow-up. Results showed that there was a significant interaction effect of treatment type and sex, such that women who received CM decreased their discounting more than women who did not. However, this effect was not found among men. Participants who discounted most at intake showed the greatest delay discounting decreases. Lastly, smoking abstinence did not affect changes in delay discounting. The current results suggest that CM intervention may have a differential effect on delay-discounting changes as a function of sex. This finding supports the relevance of considering the effect of individual variables when assessing changes in delay discounting due to clinical interventions. PMID- 26375516 TI - Cat ownership and schizophrenia. PMID- 26375515 TI - Effects of repeated morphine on intracranial self-stimulation in male rats in the absence or presence of a noxious pain stimulus. AB - Research on opioid analgesics such as morphine suggests that expression of abuse related effects increases with repeated exposure. Repeated exposure to opioids often occurs clinically in the context of pain management, and a major concern for clinicians is the risk of iatrogenic addiction and dependence in patients receiving opioids for treatment of pain. This study compared abuse-related morphine effects in male rats in an intracranial self-stimulation (ICSS) procedure after repeated treatment either with morphine alone or with morphine in combination with a repeated noxious stimulus (intraperitoneal administration of dilute acid). The study also permitted comparison of morphine potency and effectiveness to block acid-induced depression of ICSS (antinociception) and to produce enhanced facilitation of ICSS (abuse-related effect). There were 3 main findings. First, initial morphine exposure to drug naive rats did not produce abuse-related ICSS facilitation. Second, repeated daily treatment with 3.2 mg/kg/day morphine for 6 days increased expression of ICSS facilitation. This occurred whether morphine was administered in the absence or presence of the noxious stimulus. Finally, a lower dose of 1.0 mg/kg/day morphine was sufficient to produce antinociception during repeated acid treatment, but this lower dose did not reliably increase abuse-related morphine effects. Taken together, these results suggest that prior morphine exposure can increase abuse liability of subsequent morphine treatments even when that morphine exposure occurs in the context of a pain state. However, it may be possible to relieve pain with relatively low morphine doses that do not produce increases in abuse-related morphine effects. PMID- 26375519 TI - An abridged version of the Cochrane review of exercise therapy for chronic fatigue syndrome. AB - BACKGROUND: Chronic fatigue syndrome (CFS), also known as myalgic encephalomyelitis (ME) is estimated to affect between 2 in 1000 and 2 in 100 adults depending on how diagnostic criteria are applied. Patients with CFS have long-lasting fatigue in addition to symptoms including muscle pain, concentration and sleep problems. These symptoms cause significant disability and distress to the people affected. This review is an update of a previous Cochrane review (2004) that showed that exercise therapy was a promising treatment for adults with CFS. AIM: The aim of this systematic review was to determine the effects of exercise therapy for patients with CFS. DESIGN: Systematic review. SETTING: Health care settings. POPULATION: Participants over 18 years with a primary diagnosis of CFS, able to attend an outpatient clinic for exercise therapy, were included. METHODS: We searched electronic databases, including SPORTDiscus, up to May 2014 using a comprehensive list of free-text terms for CFS and exercise. Randomized clinical trials from all health care settings with participants over 18 years with a primary diagnosis of CFS, able to attend an outpatient clinic for exercise therapy, were included. We have included 8 randomized clinical studies that reported data from 1518 participants. Seven studies used aerobic exercise such as walking, swimming, or cycling and one study used non-aerobic exercise. The exercise therapies lasted between 12 and 26 weeks. Meta-analysis was done when appropriate. RESULTS: Exercise therapy was more effective at reducing fatigue than "passive" treatments or no treatment at end of treatment. Exercise therapy also had a positive effect on people's daily physical functioning, sleep quality and self-rated overall health. Nearly twice as many patients reported improvement self-rated overall health after exercise therapy (40 per 100) compared to standard treatment (22 per 100). The evidence was too sparse and/or of too low quality to conclude if exercise therapy has an effect on pain, quality of life, anxiety or depression. Exercise therapy was not found to worsen symptoms for people with CFS, while serious side effects were rare in all exercise and comparison groups. CONCLUSIONS: Patiens with CFS may generally benefit from and feel less fatigued following exercise therapy, and no evidence suggests that exercise therapy may worsen outcomes. CLINICAL REHABILITATION IMPACT: Exercise therapy should be considered. PMID- 26375518 TI - Alterations in DNA methylation corresponding with lung inflammation and as a biomarker for disease development after MWCNT exposure. AB - Use of multi-walled carbon nanotubes (MWCNT) is growing which increases occupational exposures to these materials. Their toxic potential makes it important to have an in-depth understanding of the inflammation and disease that develops due to exposure. Epigenetics is one area of interest that has been quickly developing to assess disease processes due to its ability to change gene expression and thus the lung environment after exposure. In this study, promoter methylation of inflammatory genes (IFN-gamma and TNF-alpha) was measured after MWCNT exposure using the pyrosequencing assay and found to correlate with initial cytokine production. In addition, methylation of a gene involved in tissue fibrosis (Thy-1) was also altered in a way that matched collagen deposition. In addition to using epigenetics to better understand disease processes, it has also been used as a biomarker of exposure and disease. In this study, global methylation was determined in the lung to ascertain whether MWCNT alter global methylation at the site of exposure and if those alterations coincide with disease development. Then, global methylation levels were determined in the blood to ascertain whether global methylation could be used as a biomarker of exposure in a more easily accessible tissue. Using the LuUminometric Methylation Assay (LUMA) and 5-Methylcytosine (5-mC) Quantification assay, we found that MWCNT lead to DNA hypomethylation in the lung and blood, which coincided with disease development. This study provides initial data showing that alterations in gene specific methylation correspond with an inflammatory response to MWCNT exposure. In addition, global DNA methylation in the lung and blood coincides with MWCNT induced disease development, suggesting its potential as a biomarker of both exposure and disease development. PMID- 26375520 TI - Dimethylarginine dimethylaminohydrolase-1 mediates inhibitory effect of interleukin-10 on angiotensin II-induced hypertensive effects in vascular smooth muscle cells of spontaneously hypertensive rats. AB - In hypertension studies, anti-inflammatory cytokine interleukin-10 (IL-10) has been shown to prevent angiotensin II (Ang II)-induced vasoconstriction and regulate vascular function by down-regulating pro-inflammatory cytokine and superoxide production in vascular cells. However, little is known about the mechanism behind the down-regulatory effect of IL-10 on Ang II-induced hypertensive mediators. In this study, we demonstrated the effects of IL-10 on expression of dimethylarginine dimethylaminohydrolase (DDAH)-1, a regulator of NO bioavailability, as well as the down-regulatory mechanism of action of IL-10 in relation to Ang II-induced hypertensive mediator expression and cell proliferation in vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rats (SHR). IL-10 increased DDAH-1 but not DDAH-2 expression and increased DDAH activity. Additionally, IL-10 attenuated Ang II-induced DDAH-1 inhibition in SHR VSMCs. Increased DDAH activity due to IL-10 was mediated mainly through Ang II subtype II receptor (AT2 R) and AMP-activated protein kinase (AMPK) activation. DDAH-1 induced by IL-10 partially mediated the inhibitory action of IL-10 on Ang II-induced 12-lipoxygenase (LO) and endothelin (ET)-1 expression in SHR VSMCs. In addition, the inhibitory effect of IL-10 on proliferation of Ang II-induced VSMCs was mediated partially via DDAH-1 activity. These results suggest that DDAH-1 plays a potentially important role in the anti hypertensive activity of IL-10 during Ang II-induced hypertension. PMID- 26375517 TI - Pathomimetic cancer avatars for live-cell imaging of protease activity. AB - Proteases are essential for normal physiology as well as multiple diseases, e.g., playing a causative role in cancer progression, including in tumor angiogenesis, invasion, and metastasis. Identification of dynamic alterations in protease activity may allow us to detect early stage cancers and to assess the efficacy of anti-cancer therapies. Despite the clinical importance of proteases in cancer progression, their functional roles individually and within the context of complex protease networks have not yet been well defined. These gaps in our understanding might be addressed with: 1) accurate and sensitive tools and methods to directly identify changes in protease activities in live cells, and 2) pathomimetic avatars for cancer that recapitulate in vitro the tumor in the context of its cellular and non-cellular microenvironment. Such avatars should be designed to facilitate mechanistic studies that can be translated to animal models and ultimately the clinic. Here, we will describe basic principles and recent applications of live-cell imaging for identification of active proteases. The avatars optimized by our laboratory are three-dimensional (3D) human breast cancer models in a matrix of reconstituted basement membrane (rBM). They are designated mammary architecture and microenvironment engineering (MAME) models as they have been designed to mimic the structural and functional interactions among cell types in the normal and cancerous human breast. We have demonstrated the usefulness of these pathomimetic avatars for following dynamic and temporal changes in cell:cell interactions and quantifying changes in protease activity associated with these interactions in real-time (4D). We also briefly describe adaptation of the avatars to custom-designed and fabricated tissue architecture and microenvironment engineering (TAME) chambers that enhance our ability to analyze concomitant changes in the malignant phenotype and the associated tumor microenvironment. PMID- 26375521 TI - Cepharanthine mitigates pro-inflammatory cytokine response in lung injury induced by hemorrhagic shock/resuscitation in rats. AB - BACKGROUND: Cepharanthine possesses strong anti-inflammation capacity. We sought to clarify whether cepharanthine could mitigate pro-inflammatory cytokine production in acute lung injury induced by hemorrhagic shock/resuscitation (HS/RES). The involvement of heme oxygenase-1 (HO-1) was also investigated. METHODS: Male Sprague Dawley rats were allocated to receive HS/RES, HS/RES plus iv cepharanthine or HS/RES plus cepharanthine plus the HO-1 activity inhibitor tin protoporphyrin (SnPP) and denoted as the HS/RES, HS/RES+CEP, and HS/RES+CEP+SnPP group, respectively. HS/RES was achieved by blood drawing to lower mean arterial pressure (40-45 mmHg for 60 min) followed by shed blood/saline mixtures re-infusion. The rats were monitored for another 5h before sacrifice. RESULTS: Arterial blood gas, lung permeability and histologic assays (including histopathology, neutrophil infiltration, and lung water content) confirmed that HS/RES induced significant lung injury. Significant increases in pulmonary levels of tumor necrosis factor-alpha, interleukin-1beta, interleukin 6, prostaglandin E2 and cyclooxygenase-2 confirmed that HS/RES induced a significant inflammatory response in the lungs. Cepharanthine significantly attenuated the pulmonary pro-inflammatory cytokine production and lung injury induced by HS/RES. However, the protective effects of cepharanthine were blocked by SnPP, the potent HO-1 activity inhibitor. CONCLUSION: Cepharanthine significantly mitigates pro-inflammatory cytokine response in acute lung injury induced by HS/RES in rats. The mechanism may involve the HO-1 pathway. PMID- 26375522 TI - Association between polymorphisms of interleukin 12 and rheumatoid arthritis associated biomarkers in a Chinese population. AB - INTRODUCTION: The aim of the present study was to examine the association between polymorphisms of interleukin 12 (IL-12) and rheumatoid arthritis (RA) associated biomarkers in a Chinese population. MATERIALS AND METHODS: We studied IL-12A rs2243115 T/G and IL-12B rs3212227 A/C polymorphisms in 615 RA patients and 839 controls in a Chinese population. Genotyping was done by a custom-by-design 48 Plex SNPscanTM Kit. The plasma level of IL-12 was measured by an enzyme-linked immune-sorbent assay in 90 RA patients and 90 controls. Clinical data with other potential diagnostic value were provided by the physicians. RESULTS: A significantly increased risk for RA associated with the IL-12A rs2243115 GG (GG versus TT: OR=4.81, 95% CI 1.33-17.36, P=0.017; and GG versus TG+TT: OR=4.55, 95% CI 1.27-16.36, P=0.020) genotype was evident among rheumatoid factor (RF) negative patients, and with the IL-12B rs3212227 AC (AC versus AA) and AC+CC (AC+CC versus AA) genotypes were evident among older patients (OR=1.48, 95% CI 1.06-2.06, P=0.020), RF positive patients (OR=1.35, 95% CI 1.04-1.75, P=0.026) and anti-cyclic citrullinated peptide antibodies (ACPA) negative patients (OR=1.53, 95% CI 1.11-2.10, P=0.009). The plasma level of IL-12 was significantly higher in RA patients (P<0.001). IL-12 plasma level of IL-12A rs2243115 TT (P<0.001) and IL-12B rs3212227 C allele (P<0.001) were significantly higher in RA patients than controls respectively. The plasma level of IL-12 of RF positive RA patients was significantly higher than RF negative patients (P=0.008), especially in rs3212227 AC patients (P=0.01). CONCLUSIONS: These findings suggested that the functional single nucleotide polymorphism (SNP) IL-12A rs2243115 GG genotype may increase the risk of RA in RF negative patients, and the IL-12B rs3212227 AC and AC+CC genotypes are associated with RA risk in older patients, RF positive patients and ACPA negative patients. The IL-12A rs2243115 T/G and IL-12B rs3212227 A/C allele might also impact the inflammatory reaction of IL-12 in patients with RA. PMID- 26375523 TI - Fat Necrosis Presenting as a Soft Tissue Mass. PMID- 26375524 TI - Cost-effectiveness of MRI to Assess for Posttraumatic Ligamentous Cervical Spine Injury. PMID- 26375525 TI - Barriers to Women Entering the Field of Orthopedic Surgery. PMID- 26375526 TI - Second-Generation Versus First-Generation Cementless Tapered Wedge Femoral Stems. AB - Clinical outcomes of a new second-generation proximally coated, tapered wedge cementless stem were compared with those of its predecessor regarding (1) all cause implant survivorship; (2) objective and subjective outcomes; (3) complications; and (4) radiographic features. Patients who underwent a primary total hip arthroplasty with the second-generation stem (68 hips) were compared with those who received the first-generation stem (136 hips) at a mean follow-up of 3.5 years. Although the first-generation stem was designed in the traditional manner, the second-generation stem was shortened to accommodate all surgical approaches and designed using a computed tomography scan-based database to enhance fit. The second-generation stem had survivorship, functional, and subjective outcomes similar to those of the first-generation stem. PMID- 26375527 TI - Conventional Versus Cross-Linked Polyethylene for Total Hip Arthroplasty. AB - The clinical and radiographic outcomes of 88 patients who underwent primary total hip arthroplasty with either conventional polyethylene or cross-linked polyethylene (XLPE) from the same manufacturer were compared. There were no significant differences between the 2 subpopulations regarding average age, gender, side affected, or prosthetic stem and cup size. The average follow-up was 104 months (range, 55 to 131 months). To the authors' knowledge, this is the longest follow-up for this particular insert. Clinical and radiographic evaluations were performed at 1, 3, 6, and 12 months and then annually. Results showed that XLPE has a significantly greater wear reduction than that of standard polyethylene in primary total hip arthroplasty. At the longest available follow up for these specific inserts, XLPE proved to be effective in reducing wear. PMID- 26375528 TI - Current Arthroscopic Concepts in Repairing Posterior Cruciate Ligament Tibial Sided Avulsions. AB - Posterior cruciate ligament (PCL) injuries are extremely rare and most commonly occur in the trauma setting. They can lead to instability, pain, diminished function, and eventual arthrosis. Several techniques of arthroscopic PCL repair for tibial-sided bony avulsions have been described in the literature; however, no single technique has emerged as the gold standard to predictably restore posterior knee stability, PCL function, and knee biomechanics. The authors believe that the best results will come from procedures that re-create the normal human anatomy and knee kinematics. In this article, 3 arthroscopic methods of PCL avulsion repairs performed at 2 academic institutions are analyzed. The techniques described here provide good options for the treatment of these injuries. PMID- 26375529 TI - Operative Management Options for Traumatic Anterior Shoulder Instability in Patients Younger Than 30 Years. AB - Anterior instability of the glenohumeral joint is a relatively common problem in the young population. Identification and treatment is essential to reduce the risk of recurrent instability, whether that is re-dislocation or subluxation events. Non-operative treatment for first-time dislocations was the classic option; however, a relatively high rate of recurrent dislocations has led to earlier operative management in some cases. Surgical treatment through either an open or arthroscopic approach has continued to be an area of research and debate. The decision depends partly on the exact etiology of the instability and the extent of soft tissue or bony deficiency. As arthroscopic techniques and experience improve, surgical procedures for arthroscopic anterior shoulder instability continue to evolve. This review serves as an in-depth overview of the treatment options for traumatic anterior shoulder instability in the patient younger than 30 years, generally focusing on non-rotator cuff-associated etiologies for recurrent instability. PMID- 26375530 TI - Suture Technique Influences the Biomechanical Integrity of Pectoralis Major Repairs. AB - Pectoralis major ruptures occur in large, muscular individuals, and repair constructs may experience significant tension. Four different suture techniques were evaluated biomechanically to determine the effect of suture technique on optimizing fixation strength. Forty fresh-frozen cadaveric shoulders were repaired using endosteal buttons. The control group was repaired with #2 polyblend suture in a modified Mason-Allen stitch configuration. The triple group was repaired using the same suture and configuration, but with the addition of triple-loaded buttons. The configuration group was repaired using the same suture in a Krackow/Bunnell configuration. The tape group was repaired using 2-mm polyethylene tape and #5 polyblend suture in the Krackow/Bunnell configuration. Under cyclic loading, there was no significant difference between groups. Under load-to-failure testing, the tape group withstood a significantly greater maximum load (726.0+/-90.0 N) than the control and triple groups (330.2+/-20.2 and 400.2+/-35.2 N, respectively; P<.005), and similar load to the configuration group (509.9+/-68.6 N; P=.16). The configuration group failed via suture breakage (9/10); the other groups failed via suture pullout, in which suture pulled through tendon (26/30). Pectoralis major repair in a running, locked configuration appears to improve biomechanical performance by preventing suture pullout. Use of a polyethylene tape construct demonstrates the potential for improved failure loads, but its role remains undefined. PMID- 26375531 TI - Biopsies in the Community Lead to Postoperative Complications in Soft Tissue Sarcomas. AB - Percutaneous biopsies allow for precise diagnosis in soft tissue sarcomas and have a low rate of complications. However, it is unknown whether biopsies performed in a community setting lead to higher rates of wound complications at the time of resection. The goal of this study was to determine whether percutaneous biopsies performed at a sarcoma center have lower rates of wound complications compared with those performed in the community setting. A total of 125 patients with soft tissue sarcomas were treated with neoadjuvant radiation followed by limb-sparing resection. Of these, 92 underwent percutaneous biopsy. Patient, demographic, and treatment variables and postoperative wound complications were reviewed. Predictors of wound complications were evaluated with Fisher's exact test for univariate analysis and with logistic regression for multivariate analysis. The wound complication rate was 27% for open or percutaneous biopsies. When only percutaneous biopsies were assessed, the wound complication rate was 25%. The wound complication rate for percutaneous biopsies was 18% when the biopsy was performed at the authors' sarcoma center and 46% when the biopsy was performed in the community setting (P=.01). The Common Terminology Criteria for Adverse Events grade 4 wound complication rate was 73% in patients who underwent percutaneous biopsy at a community hospital vs 14% in those who underwent percutaneous biopsy at the authors' sarcoma center (P=.005). Multivariate analysis showed that lower-extremity soft tissue sarcomas (P=.03) and biopsies performed in the community setting (P=.01) had an increased rate of postoperative wound complications. Percutaneous biopsies performed at community hospitals had an increased incidence of grade 4 postoperative wound toxicity compared with biopsies done at tertiary centers. These wound results confirmed previous recommendations that biopsy of soft tissue sarcomas should be performed at an experienced sarcoma center. PMID- 26375532 TI - Anterolateral Versus Medial Plating of Distal Extra-articular Tibia Fractures: A Biomechanical Model. AB - Both medial and anterolateral plate applications have been described for the treatment of distal tibia fractures, each with distinct advantages and disadvantages. The objective of this study was to compare the biomechanical properties of medial and anterolateral plating constructs used to stabilize simulated varus and valgus fracture patterns of the distal tibia. In 16 synthetic tibia models, a 45 degrees oblique cut was made to model an Orthopedic Trauma Association type 43-A1.2 distal tibia fracture in either a varus or valgus injury pattern. Each fracture was then reduced and plated with a precontoured medial or anterolateral distal tibia plate. The specimens were biomechanically tested in axial and torsional loading, cyclic axial loading, and load to failure. For the varus fracture pattern, medial plating showed less fracture site displacement and rotation and was stiffer in both axial and torsional loading (P<.05). For the valgus fracture pattern, there was no statistically significant difference between medial and anterolateral plating. There were no significant differences between the 2 constructs for either fracture pattern with respect to ultimate load, displacement, or energy absorption in load to failure testing. When used to stabilize varus fracture patterns, medial plates showed superior biomechanical performance compared with anterolateral plates. In this application, the medial plates functioned in anti-glide mode. For valgus fracture patterns, no biomechanical differences between anterolateral and medial plating were observed. In clinical practice, surgeons should take this biomechanical evidence into account when devising a treatment strategy for fixation of distal tibia fractures. PMID- 26375533 TI - Modified Murray Technique for Carpal Navicular Nonunion. AB - The authors report the results of long-term follow-up in 29 patients treated for non-union of the carpal navicular with a modified Murray technique performed through a lateral approach. Mean patient age at surgery was 22.5 years. Average time from injury to surgery for nonunion was 18 months. In 5 cases, mild signs of osteoarthritis of the radioscaphoid joint (scaphoid nonunion advanced collapse [SNAC] stage I) were present before surgery, and in 2 cases, radiographic signs of avascular necrosis of the proximal nonunion fragment were evident. In all cases, a corticocancellous nonvascularized bone graft taken from the distal part of the ipsilateral radius was used. Mean follow-up was 11.2 years. Nonunion had healed in 93.1% of cases. At follow-up, the 2 patients in whom nonunion had not healed had severe painful osteoarthritis of the wrist (SNAC stage IV). Twenty patients were asymptomatic, and 5 had occasional pain in the wrist. Wrist range of motion was restricted in all patients compared with the contralateral side. Mild osteoarthritis was observed in 6 patients (SNAC stage I). The average Disabilities of the Arm, Shoulder and Hand score was 8.7 of 100. The modified Murray technique is reliable for treating nonunion of the carpal navicular. The union rate is high, and the incidence of wrist osteoarthritis is low compared with other studies. Early diagnosis and treatment of nonunion (a short interval between fracture and surgery) can minimize the risk of degenerative joint disease. Avascular necrosis of the proximal fragment is not an absolute contraindication to surgery. PMID- 26375534 TI - Conversion to Reverse Shoulder Arthroplasty: Humeral Stem Retention Versus Revision. AB - As the volume of shoulder arthroplasty procedures performed in the United States continues to increase, the predicted number of revision shoulder arthroplasties grows even higher. Conversion of failed shoulder arthroplasty to reverse total shoulder arthroplasty has become common. Many commercially available shoulder arthroplasty systems now offer a platform humeral stem that is used for both anatomic shoulder arthroplasty and reverse total shoulder arthroplasty. This study investigated whether retaining the humeral stem offers advantages over revising the humeral stem in conversion of failed shoulder arthroplasty to reverse total shoulder arthroplasty. The study included 26 patients (mean age, 68.46 years) with failed shoulder arthroplasty who underwent conversion to reverse total shoulder arthroplasty with a minimum 2-year follow-up (mean, 34.38 months). Patients who had retention of the humeral stem were compared with those who had stem revision. Humeral stem retention was associated with a significantly shorter operative time (178.92 vs 237 minutes, P=.02). Decreases in blood loss, complications, and length of hospitalization were observed, but the differences were not statistically significant. Minimal differences were observed for patient reported outcomes. Of patients undergoing humeral stem removal, 21.4% had an intraoperative humeral shaft or tuberosity fracture compared with none in the stem retention group. Humeral stem retention was associated with decreased operative time compared with humeral stem revision in the conversion of failed shoulder arthroplasty to reverse total shoulder arthroplasty. The use of a platform shoulder arthroplasty system may benefit patients with failed shoulder arthroplasty undergoing conversion to reverse total shoulder arthroplasty by avoiding humeral stem revision. PMID- 26375535 TI - Population-Based Epidemiology of Tibial Plateau Fractures. AB - Although epidemiologic studies of tibial plateau fractures have been conducted, none have included geographically defined populations or a validated fracture classification based on computed tomography (CT). The goals of this study were to provide up-to-date information on the incidence and basic epidemiology of tibial plateau fractures in a large unselected patient population and to report the mechanisms of injury involved and the distribution of fractures according to a validated CT-based fracture classification. The authors conducted a population based epidemiologic study of all patients treated for tibial plateau fracture over a 6-year period from 2005 to 2010. The study was based on an average background population of 576,364 citizens. A retrospective review of hospital records was performed. During this time, a total of 355 patients were treated for tibial plateau fracture. This group included 166 men and 189 women, and mean age was 52.6 years (SD, 18.3). The most common fracture type was AO type 41-B3, representing 35% of all tibial plateau fractures. The second most common fracture type was AO type 41-C3, representing 17% of all tibial plateau fractures. The incidence of tibial plateau fractures was 10.3 per 100,000 annually. Compared with women, men younger than 50 years had a higher incidence of fractures. The incidence of fractures increased markedly in women older than 50 years but decreased in men older than 50 years. In both sexes, the highest frequency was between the ages of 40 and 60 years. PMID- 26375536 TI - Septic Arthritis in Infants Younger Than 3 Months: A Retrospective Review. AB - Septic arthritis in infants is rare and can be difficult to diagnose. This study reviewed a series of patients younger than 3 months to identify factors that may assist in early diagnosis and treatment. A query of records at a large Midwestern pediatric hospital (1994-2010) was performed to identify all patients younger than 3 months at the time of diagnosis. Analysis included birth history, joint involvement, physical examination findings, laboratory results, imaging results, method of treatment, and outcome. In 14 cases (11 boys, 3 girls; mean age at diagnosis, 42.2 days), complete records were available for review. Involved joints included the knee, hip, and shoulder. The most common findings on physical examination were decreased range of motion (100%), tenderness (100%), and swelling (71.4%). Mean temperature was 38.5 degrees C. Mean white blood cell count was 18.5 K/uL, mean erythrocyte sedimentation rate was 48.9 mm/h, and mean C-reactive protein level was 6.1 mg/dL. More than half (57.1%) of joint aspirates grew positive cultures, and 41.7% of blood cultures had positive results. Causative organisms were group B streptococcus, methicillin-sensitive Staphylococcus aureus, Haemophilus influenzae, Streptococcus pneumoniae, Salmonella enterica, and Candida albicans. The most common physical examination findings in infants younger than 3 months with septic arthritis include tenderness, decreased range of motion, and swelling. White blood cell count, C reactive protein level, and erythrocyte sedimentation rate are likely to be elevated, but these findings should be used in combination with findings on physical examination and radiographic studies to aid in diagnosis. PMID- 26375537 TI - Surgical Treatment for Central Calcified Thoracic Disk Herniation: A Novel L Shaped Osteotome. AB - Few reports are available on the posterior transfacet approach for the treatment of central calcified thoracic disk herniation (TDH). The objective of this study was to assess outcomes and complications in a consecutive series of patients with TDH who underwent posterior transfacet decompression and diskectomy with segmental instrumentation and fusion. The data for 27 patients (16 males and 11 females) were retrospectively reviewed and analyzed, including clinical presentation, blood loss, operative time, pre- and postoperative complications, visual analog scale, Japanese Orthopedic Association (JOA) score, and Frankel grade. All patients underwent trans-facet decompression and segmental instrumentation with interbody fusion. Mean patient age at surgery was 55.2 years (range, 21-81 years). Average follow-up was 30+/-19 months (range, 12-50 months). All patients were successfully treated with posterior decompression and segmental instrumentation with interbody fusion. Average operative time was 124+/-58 minutes (range, 87-180 minutes). Mean blood loss was 439+/-225 mL (range, 300 1500 mL). Average pre- and postoperative JOA scores were 4.12+/-0.87 and 8.01+/ 0.97 points, respectively. Overall JOA scores showed a significant postoperative improvement. Overall recovery rates were excellent in 12 patients, good in 6, fair in 5, and unchanged in 1. No patient was classified as worse. The results suggest that the posterior approach using a special L-shaped osteotome is feasible. No major complications occurred while achieving adequate decompression for central calcified TDH. PMID- 26375538 TI - Complication Risk After Treatment of Intertrochanteric Hip Fractures in the Medicare Population. AB - The study evaluated the incidence of and complications associated with the use of an intramedullary nail vs open reduction and internal fixation (ORIF) with a sliding compression hip screw and plate in treating intertrochanteric fractures. The authors hypothesized that the biomechanically stronger and less invasive intramedullary nail would have superior results and fewer complications compared with ORIF. Patients followed for up to 1 year postoperatively were identified from the 5% nationwide sample of Medicare administrative claims data (1998-2007) using the corresponding International Classification of Diseases, 9th revision, Clinical Modification, codes 820.21 and 820.31. There were 9157 patients treated with intramedullary nails and 27,687 treated with compression screw and plate fixation. Intertrochanteric hip fractures treated with an intramedullary nail during this period increased from 3.3% to 63.1% compared with ORIF. Patients treated with an intramedullary nail had a higher adjusted risk of pulmonary embolism at 90 days (P=.003) and a higher risk of mortality at 1 year (P<.001) compared with those treated with ORIF. Patients who underwent intramedullary nailing during 2006 to 2007 had a lower adjusted risk of conversion to total hip replacement at 1 year (P=.037) compared with those who had ORIF. Over the decade of the study, intramedullary nail usage increased 59.8% compared with ORIF. Increased use of intramedullary nails compared with ORIF has not shown improved outcomes or decreased complications in patients with intertrochanteric hip fractures. The increased use of intramedullary nails for intertrochanteric hip fractures appears to be multifactorial, including the less invasive nature of the surgery and increased experience with the closed surgical technique. PMID- 26375539 TI - Physician-Hospital Alignment in Orthopedic Surgery. AB - The concept of "alignment" between physicians and hospitals is a popular buzzword in the age of health care reform. Despite their often tumultuous histories, physicians and hospitals find themselves under increasing pressures to work together toward common goals. However, effective alignment is more than just simple cooperation between parties. The process of achieving alignment does not have simple, universal steps. Alignment will differ based on individual situational factors and the type of specialty involved. Ultimately, however, there are principles that underlie the concept of alignment and should be a part of any physician-hospital alignment efforts. In orthopedic surgery, alignment involves the clinical, administrative, financial, and even personal aspects of a surgeon's practice. It must be based on the principles of financial interest, clinical authority, administrative participation, transparency, focus on the patient, and mutual necessity. Alignment can take on various forms as well, with popular models consisting of shared governance and comanagement, gainsharing, bundled payments, accountable care organizations, and other methods. As regulatory and financial pressures continue to motivate physicians and hospitals to develop alignment relationships, new and innovative methods of alignment will also appear. Existing models will mature and evolve, with individual variability based on local factors. However, certain trends seem to be appearing as time progresses and alignment relationships deepen, including regional and national collaboration, population management, and changes in the legal system. This article explores the history, principles, and specific methods of physician hospital alignment and its critical importance for the future of health care delivery. PMID- 26375540 TI - Epidemiology of Aquatic and Recreational Water Sport Injuries: A Case-Control Analysis. AB - The purposes of the current investigation are to evaluate the epidemiology of water sport injuries at a coastal tertiary trauma center and to determine the association of these activities with spinal column injury and to determine whether aquatic trauma injuries differ significantly from those that occur terrestrially. A retrospective review of a consecutive series of 105 patients with aquatic-based mechanisms of injury admitted to a Level II trauma center over a 3-year period, as well as a matched control cohort with terrestrial-based mechanisms of injury, was conducted. Patients were treated at a Level II trauma center from January 1, 2008, to December 31, 2010. All patients received a full trauma work-up on arrival. Patients were identified retrospectively from a prospectively collected database (N=5298). Eligible patients were identified from billing/coding data as having mechanisms of injury related to an aquatic setting. Patients were evaluated using standard trauma protocols. Spinal column and cord injury occurrence and differences between groups were reviewed. Personal watercrafts accounted for the majority of injuries (n=39). Cervical (33.3%), closed-head (25.7%), and thoracolumbar (21.9%) injuries accounted for the majority of injury types. The cervical spinal column and the spinal cord were at an increased risk of injury in the aquatic injury cohort (P<.0001). The current data show the high incidence of spinal column and cord injuries in this patient population relative to controls. Practitioners who care for trauma patients near an aquatic environment should be aware of the high prevalence of these injuries, with proper spinal cord preservation protocols in place to optimize outcome. PMID- 26375541 TI - Patient-Controlled Transdermal Fentanyl Versus Intravenous Morphine Pump After Spine Surgery. AB - Patient-controlled analgesia (PCA) is regularly used to manage pain following major surgery. The fentanyl hydrochloride iontophoretic transdermal system (ITS) was developed to overcome some of the limitations of intravenous (IV) PCA. The small, self-adhesive, needle-free disposable system is applied to the skin on the upper arm or chest and is controlled by patients clicking a button on the device. The authors identified patients who were underwent spinal surgery from 2 prior multicenter, randomized studies and analyzed their data. Of the 1296 patients in the original trials, 170 underwent spine surgery procedures: 90 were randomized to the fentanyl ITS (40 mcg/activation) and 80 to IV PCA morphine (1 mg/dose). More patients treated with the fentanyl ITS rated their method of pain control as "excellent" across all time points, but differences did not reach statistical significance. However, investigators' ratings of "excellent" satisfaction with study treatment were significantly higher for the fentanyl ITS. Discontinuation rates and overall adverse event rates were similar between groups. The only significant difference was that patients treated with the fentanyl ITS had a higher rate of application site reactions than infusion site reactions in the IV PCA morphine group; the reactions were typically mild-to-moderate erythema that resolved shortly after removal of the fentanyl ITS device and did not require further treatment. Ratings of satisfaction with pain control method were consistently higher for the fentanyl ITS than the IV PCA morphine. The 2 groups had a similar safety profile. These results suggest that the fentanyl ITS appears to be a safe, efficacious alternative to IV PCA in spine surgery patients. PMID- 26375542 TI - Management of Humeral Shaft Fractures With Intramedullary Interlocking Nail Versus Locking Compression Plate. AB - Surgical fixation of humeral shaft fractures generally involves plating or nailing. It is unclear whether one method is more effective than the other. The aim of this study was to compare the results of the intramedullary nail and locking compression plate for the treatment of humeral shaft fractures. A total of 60 patients with humeral shaft fractures were randomized to undergo surgery with an intramedullary interlocking nail (n=30) or locking compression plate (n=30). The outcome was assessed in terms of intraoperative blood loss, operative time, hospital stay, union time, union rate, functional outcome, and incidence of complications. Functional outcome was assessed using the Constant score and the American Shoulder and Elbow Surgeons (ASES) score. Intraoperative blood loss, operative time, and hospital stay in group A (intramedullary interlocking nail) were significantly lower than those in group B (locking compression plate). No statistically significant difference was found regarding the union rate, mean Constant score, and mean ASES score between the groups. The average union time was found to be significantly lower for the intramedullary interlocking nail compared with the locking compression plate. The incidence of complications such as radial nerve palsy was found to be higher with the locking compression plate compared with the intramedullary interlocking nail. The intramedullary interlocking nail can be considered a better surgical option for the management of humeral shaft fractures because it offers decreased intraoperative blood loss; shorter operative times, hospital stays, and union times; and a lower incidence of serious complications such as radial nerve palsy. PMID- 26375543 TI - Predicting Postoperative C5 Palsy Using Preoperative Spinal Cord Rotation. AB - The development of C5 nerve palsy after cervical decompression surgery has been well documented. The goal of this study was to determine whether preoperative spinal cord rotation could be used as a predictor of C5 palsy in patients who underwent posterior cervical decompression at C4-C6. The authors reviewed the records of 72 patients who had posterior decompression and 77 patients who had anterior decompression. With the patients undergoing anterior decompression used as a control group, magnetic resonance imaging scans were analyzed for area of the spinal cord, anterior-posterior diameter, and cord rotation relative to the vertebral body. The rate of C5 palsy was 7.3%. Average degrees of rotation were 3.83 degrees +/-2.47 degrees and 3.45 degrees +/-2.23 degrees in the anterior and posterior groups, respectively. A statistically significant association was detected between degree of rotation and C5 palsy. Point-biserial correlations were 0.58 (P<.001) and 0.60 (P<.001) in the anterior and posterior groups, respectively. With a diagnostic cutoff of 6 degrees , the sensitivity and specificity of identifying patients with C5 palsy in the posterior group were 0.67 (95% confidence interval, 0.24-0.94) and 0.95 (95% confidence interval, 0.86 0.98), respectively. The results suggested that preoperative spinal cord rotation may be a valid predictor of C5 nerve palsy after posterior cervical decompression. With mild rotation defined as less than 6 degrees , moderate rotation as 6 degrees to 10 degrees , and severe rotation as greater than 10 degrees , the prevalence of C5 palsy in the posterior group was 2 of 65 for mild rotation, 3 of 6 for moderate rotation, and 1 of 1 for severe rotation. PMID- 26375544 TI - Imaging of the Rotator Cuff With Optical Coherence Tomography. AB - This study evaluated the utility of optical coherence tomography (OCT) in imaging porcine and human rotator cuff (RTC) tissue, analyzed its effectiveness in identifying clinical pathology, and correlated these findings with histologic examination. Twelve human cadaveric and 6 porcine shoulders were evaluated. Six millimeter-wide bone sections were harvested from the proximal humerus of each specimen, with each containing the entire enthesis of the respective RTC tendon, as well as 2 cm of tendon medial to the enthesis. Only the supraspinatus tendon was evaluated in the human specimens, whereas the enthesis of multiple RTC tendons were evaluated in the porcine model. All specimens were imaged using OCT and correlated with histologic evaluation. Optical coherence tomography evaluation of macroscopically healthy tissue consistently showed an easily identifiable banding pattern (birefringence) in contrast to a disorganized, homogeneous appearance in grossly diseased tissue. Optical coherence tomography was more effective for qualitative evaluation of RTC tissue, identification of bursal-sided RTC tears, and localization of calcific deposits, whereas intrasubstance tendon delaminations and partial articular-sided tendon avulsion lesions were relatively more difficult to identify. Optical coherence tomography correlated well with histologic evaluation in all specimens. Optical coherence tomography provides high-resolution, subsurface imaging of rotator cuff tissue in real-time to a depth of up to 4 mm with excellent correlation to histology in a cadaveric model. Optical coherence tomography could be an effective adjunctive tool for the identification and localization of rotator cuff pathology. The use of OCT in arthroscopic shoulder surgery potentially provides a minimally invasive modality for qualitative assessment of rotator cuff pathology. This may allow for a decrease in soft tissue dissection, improved qualitative assessment of cuff tissue, and improved patient outcomes. PMID- 26375545 TI - Repair of Acute-on-Chronic Subscapularis Insufficiency in an Adolescent Athlete. AB - A 13-year-old right-hand-dominant skeletally immature boy presented to the authors' clinic after being blocked during an overhead dodgeball throw and hearing an abrupt "pop" in the shoulder. He had pain in the subdeltoid region that was most prominent during sports-related activity, particularly throwing. The patient had nonoperative management of a lesser tuberosity avulsion fracture 1 year earlier after a similar injury that occurred during a basketball game. He had returned to normal sporting activity 2 months before the most recent injury. Repeat advanced imaging showed an avulsion fracture of the subscapularis tendon, with a significantly retracted 2-cm component as well as a less retracted component, suggesting acute-on-chronic injury. Given this retraction and the symptoms during throwing, the patient was counseled that surgical management would best facilitate an asymptomatic return to sports-related activity. This case showed acute-on-chronic subscapularis tendon insufficiency with avulsion of the lesser tuberosity and significant retraction of the subscapularis tendon without tearing, a rare injury pattern in adolescents. For fixation of the avulsed lesser tuberosity fracture, an open approach technique was used in which SpeedBridge (Arthrex, Naples, Florida) sutures were passed behind the bone fragment. Four anchors were placed medial and lateral to the subscapularis insertion points to create a knotless double-row footprint. Compared with the published literature, this method of subscapularis fixation offered secure anatomic repair in a time-efficient, user-friendly manner. PMID- 26375546 TI - Spontaneous Compartment Syndrome of the Hand in Systemic Sclerosis. AB - Compartment syndrome refers to a condition of compromised circulation within a limited space due to increased pressure within that space. The reduced tissue perfusion results in reduced venous drainage, leading to increased interstitial tissue pressure and subsequent compromised arterial flow. Although not as common as compartment syndrome of the leg and forearm, compartment syndrome of the hand is not rare and can lead to devastating sequelae as a result of tissue necrosis. Compartment syndrome of the hand has several etiologies, including trauma, arterial injury, thermal injury, and constrictive bandaging. The cardinal clinical sign is pain that is aggravated by passive stretching of the muscles within the involved compartments. Extremity function is usually restored with expeditious fasciotomy of the involved myofascial compartments, and complications, such as intrinsic muscular dysfunction and Volkmann's ischemic contracture, can usually be prevented. There are no reported cases of compartment syndrome of the hand in patients with systemic sclerosis or Raynaud's phenomenon. Systemic sclerosis is a form of scleroderma that affects the skin and internal organs. The limited cutaneous subset affects the skin of the extremities but is associated with a set of characteristic features that includes calcinosis, Raynaud's phenomenon, esophageal involvement, sclerodactyly, and telangiectasia. This report describes an unusual case of a patient who had spontaneous compartment syndrome of the hand. The patient's concomitant limited cutaneous systemic sclerosis may have played a role in this unusual occurrence. The diagnosis was based on the clinical picture, and the symptoms resolved after surgical decompression. PMID- 26375547 TI - Transfusion-Transmitted Babesiosis During Total Hip Arthroplasty. AB - Babesiosis is a potentially life-threatening zoonotic disease that is endemic to the northeastern United States and increasing in prevalence worldwide. Transmitted by the same Ixodes tick responsible for Lyme disease, the intraerythrocytic parasite Babesia causes a wide range of clinical presentations- from asymptomatic carriage to a fulminant course with rapid deterioration. Symptoms typically present 1 to 6 weeks after inoculation, with the gradual onset of fatigue, malaise, weakness, and intermittent or sustained fever as high as 40.9 degrees C. Severe cases are associated with parasitemia greater than 4%, alkaline phosphatase greater than 125 U/L, and white blood cell counts greater than 5*10(9)/L. Definitive diagnosis is made by microscopic examination of thin blood smears, polymerase chain reaction, and indirect immunofluorescent antibody testing. The increasing frequency of babesiosis paired with a lack of blood-donor screening assays poses a serious threat to the safety of the US blood supply. Although babesiosis is responsible for 3.6% of transfusion-related deaths, the Food and Drug Administration has yet to approve mandatory screening for the parasite in donated blood. Historically, transfusion-transmitted babesiosis has been thought to be isolated to the immunocompromised patient population. However, a recent case of transfusion-transmitted babesiosis in an immunocompetent patient following total hip arthroplasty is the first reported in the literature and may represent a growing risk to a far greater segment of the population than previously thought. This article summarizes the current state of transfusion transmitted babesiosis and the detrimental impact of this infection on blood transfusion safety. PMID- 26375548 TI - An elaboration of theory about preventing outbreaks in homogeneous populations to include heterogeneity or preferential mixing. AB - The goal of many vaccination programs is to attain the population immunity above which pathogens introduced by infectious people (e.g., travelers from endemic areas) will not cause outbreaks. Using a simple meta-population model, we demonstrate that, if sub-populations either differ in characteristics affecting their basic reproduction numbers or if their members mix preferentially, weighted average sub-population immunities cannot be compared with the proportionally mixing homogeneous population-immunity threshold, as public health practitioners are wont to do. Then we review the effect of heterogeneity in average per capita contact rates on the basic meta-population reproduction number. To the extent that population density affects contacts, for example, rates might differ in urban and rural sub-populations. Other differences among sub-populations in characteristics affecting their basic reproduction numbers would contribute similarly. In agreement with more recent results, we show that heterogeneous preferential mixing among sub-populations increases the basic meta-population reproduction number more than homogeneous preferential mixing does. Next we refine earlier results on the effects of heterogeneity in sub-population immunities and preferential mixing on the effective meta-population reproduction number. Finally, we propose the vector of partial derivatives of this reproduction number with respect to the sub-population immunities as a fundamentally new tool for targeting vaccination efforts. PMID- 26375549 TI - Vaccinia-related kinase 1 promotes hepatocellular carcinoma by controlling the levels of cell cycle regulators associated with G1/S transition. AB - We identified the specific role of vaccinia-related kinase 1 (VRK1) in the progression of hepatocellular carcinoma (HCC) and evaluated its therapeutic and prognostic potential. VRK1 levels were significantly higher in HCC cell lines than a normal hepatic cell line, and were higher in HCC than non-tumor tissue. VRK1 knockdown inhibited the proliferation of SK-Hep1, SH-J1 and Hep3B cells; moreover, depletion of VRK1 suppressed HCC tumor growth in vivo. We also showed that VRK1 knockdown increased the number of G1 arrested cells by decreasing cyclin D1 and p-Rb while upregulating p21 and p27, and that VRK1 depletion downregulated phosphorylation of CREB, a transcription factor regulating CCND1. Additionally, we found that luteolin, a VRK1 inhibitor, suppressed HCC growth in vitro and in vivo, and that the aberrant VRK1 expression correlated with poor prognostic features of HCC. High levels of VRK1 were associated with shorter overall and disease-free survival and higher recurrence rates. Taken together, our findings suggest VRK1 may act as a tumor promoter by controlling the level of cell cycle regulators associated with G1/S transition and could potentially serve as a therapeutic target and/or prognostic biomarker for HCC. PMID- 26375550 TI - Tumor driven by gain-of-function HER2 H878Y mutant is highly sensitive to HER2 inhibitor. AB - HER2, a well established oncogenic member of EGFR family, is among the most intensely investigated kinase drug targets. In contrast to hotspot mutations of EGFR, few mutations of HER2 locate in activation loop within kinase domain. We previously reported the molecular mechanism underlying hyper kinase activity of HER2H878Y, a mutation located in activation loop. However, its tumorigenicity in vivo and relevant therapeutics remain to be determined. Here, we report for the first time that HER2H878Y was tumorigenic in vivo in lung adenocarcinoma transgenic mouse model. Induced expression of HER2H878Y in lung epithelial compartments resulted in formation of poorly differentiated lung adenocarcinoma with bronchioloalveolar carcinoma (BAC) features. Strikingly, we found that these tumors depended on continuous expression of HER2H878Y for maintenance. Typical HER2 downstream signaling mediators, including PLCgamma1, STAT5 and AKT, were hyperactivated in HER2H878Y driven lung tumors. More importantly, administration of HKI-272, a tyrosine kinase inhibitor (TKI), efficiently shrank HER2H878Y driven tumors in transgenic mouse model. Moreover, we found that combinational treatment with HKI272 and mTOR inhibitor, Rapamycin, showed a superior cytotoxicity to H878Y mutant transformed cells and enhanced activity to elicit apoptosis and inhibit growth in situ in tumorous area. Our work therefore showed that HER2H878Y mutant was a reasonable drug target. Hence, our work supported the assessment of HKI-272/rapamycin treatment in clinical trials. PMID- 26375551 TI - Comparison of survival and clinicopathologic features in colorectal cancer among African American, Caucasian, and Chinese patients treated in the United States: Results from the surveillance epidemiology and end results (SEER) database. AB - African American patients of colorectal cancer (CRC) were found to have a worse prognosis than Caucasians, but it has not been fully understood about the survival difference among Chinese and these two races above. In this study, we used the Surveillance, Epidemiology and End Results database to analyze the survival difference among these three race/ethnicities in the United States. Adenocarcinoma patients of colorectal cancer with a race/ethnicity of Caucasian, Chinese and African American were enrolled for study. Patients were excluded if they had more than one primary cancer but the CRC was not the first one, had unknown cause of death or unknown survival months. The 5-year cause specific survival (CSS) was our primary endpoint. Totally, there were 585,670 eligible patients for analysis. Chinese patients had the best and African American patients had the worst 5-year CSS (66.7% vs 55.9%), P < 0.001. The 5-year CSS for Caucasian patients was 62.9%. Race/ethnicity was an independent prognostic factor in the multivariate analysis, P < 0.001. The comparison of clinicopathologic factors among these three race/ethnicities showed that the insurance coverage rate, income, percentage that completing high school and percentage of urban residence was lowest in the African American patients. Chinese patients had the highest percentage of married, while African American patients ranked lowest. More African American patients were diagnosed as stage IV and had high percentage of signet ring cell and mucinous adenocarcinoma. It is likely that biological differences as well as socioeconomic status both contribute to the survival disparity among the different race/ethnicities. PMID- 26375552 TI - Cx25 contributes to leukemia cell communication and chemosensitivity. AB - Leukemia encompasses several hematological malignancies with shared phenotypes that include rapid proliferation, abnormal leukocyte self-renewal, and subsequent disruption of normal hematopoiesis. While communication between leukemia cells and the surrounding stroma supports tumor survival and expansion, the mechanisms underlying direct leukemia cell-cell communication and its contribution to tumor growth are undefined. Gap junctions are specialized intercellular connections composed of connexin proteins that allow free diffusion of small molecules and ions directly between the cytoplasm of adjacent cells. To characterize homotypic leukemia cell communication, we employed in vitro models for both acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) and measured gap junction function through dye transfer assays. Additionally, clinically relevant gap junction inhibitors, carbenoxolone (CBX) and 1-octanol, were utilized to uncouple the communicative capability of leukemia cells. Furthermore, a qRT-PCR screen revealed several connexins with higher expression in leukemia cells compared with normal hematopoietic stem cells. Cx25 was identified as a promising adjuvant therapeutic target, and Cx25 but not Cx43 reduction via RNA interference reduced intercellular communication and sensitized cells to chemotherapy. Taken together, our data demonstrate the presence of homotypic communication in leukemia through a Cx25-dependent gap junction mechanism that can be exploited for the development of anti-leukemia therapies. PMID- 26375554 TI - Effectiveness of Labor Cervical Examination Simulation in Medical Student Education. AB - OBJECTIVE: To estimate whether simulation training improves medical students' cervical examination accuracy. BACKGROUND: The training paradigm for the labor cervical examination exposes patients to additional examinations, lacks a gold standard, and does not objectively assess trainee competence. To address these issues and optimize training, we assessed the effectiveness of cervical examination simulation in third-year medical students. METHODS: During the obstetrics and gynecology clerkship, a cohort study was performed in which third year students were assigned to receive cervical examination simulation (n=50) or vaginal delivery simulation (n=48), with each group serving as a simulation-naive control for the other skill. As a final assessment, students performed 10 cervical examinations using task trainers. Exact accuracy and accuracy within 1 cm were compared between groups. Cumulative summation analyses were performed on the cervical examination group to assess competence and the average number of repetitions needed to achieve it. RESULTS: Cervical examination students were significantly more accurate (Mann-Whitney, P<.001) in assessing dilation (73% exact, 98% within 1 cm) and effacement (83% and 100%) than vaginal delivery students (dilation 52% and 82%, effacement 51% and 96%). In the cumulative summation analyses, 65-100% of students attained competence during the clerkship depending on the level of accuracy and cervical parameter assessed. On average, competence was achieved with 27-44 repetitions. CONCLUSION: Simulation training dramatically improved student accuracy in labor cervical examinations. Because not all students achieved competence, the cumulative summation analyses suggest that more than 100 repetitions would be needed if the goal was for the entire class of students to achieve competence. LEVEL OF EVIDENCE: II. PMID- 26375555 TI - Structured Teaching of Early Pregnancy Loss Counseling. AB - OBJECTIVE: To estimate whether a novel structured curriculum could significantly improve medical student performance in early pregnancy loss counseling. BACKGROUND: Medical students receive limited exposure to early pregnancy loss counseling through real-life observation of this important skill. METHODS: A pre post control group design was used to examine early pregnancy loss counseling performance among medical students from two medical schools doing their obstetrics and gynecology rotations at the same community hospital. The study outcomes were: (1) pre-post differences in Standardized Patient Objective Structured Clinical Examination scores; (2) pre-post differences in student confidence levels; and (3) postdifferences in standardized patient empathy ratings. Both groups had similar demographics, academic parameters, and longitudinal curricula. The study group (N=39) received a curriculum of demonstration and role-playing for delivering bad news and a shared decision making model for early pregnancy loss management. The control group (N=38) received traditional instruction. RESULTS: Standardized Patient Objective Structured Clinical Examination posttest scores were significantly higher for the study group compared with the control group (94.2% compared with 69.7%, P<.001) after starting with similar pretest scores (64.0% compared with 61.6%, P=.53). Posttest confidence levels (1=high, 5=low) were significantly higher for the study compared with the control group (1.57 compared with 3.62, P<.001) after starting at similar levels (4.27 compared with 4.23, P=.79). Standardized patient empathy ratings (1=high, 5=low) were significantly higher for the study compared with the control group (1.84 compared with 2.62, P=.002). CONCLUSION: A structured curriculum for teaching early pregnancy loss counseling improved student performance on standardized Objective Structured Clinical Examinations compared with traditional instruction. Providing these counseling tools improved their confidence and empathy ratings in caring for patients with early pregnancy loss. PMID- 26375553 TI - Ovarian clear cell carcinoma meets metabolism; HNF-1beta confers survival benefits through the Warburg effect and ROS reduction. AB - Ovarian clear cell carcinoma (OCCC) constitutes one of the subtypes of ovarian cancers, but it has unique clinical, histological and biological characteristics, one of which is chemo-resistance. It is also known to develop from endometriotic cyst, a benign ovarian tumor, at relatively high frequency. Recently, it is becoming well known that most of OCCCs express HNF1beta, a transcription factor, which is closely associated with the development of liver, pancreas and kidney, as well as occurrence of familial forms of type 2 diabetes. Expression of HNF1beta is now regarded as a hallmark of this tumor. Nevertheless, exact biological function of this gene in OCCC has not been clarified. We have shown in previous studies that microenvironment in endometriotic cysts contains severe oxidative stress and OCCC develops under such stressful environment as stress resistant tumor, which may lead to chemo-resistance. We also showed that increased expression of HNF1beta facilitates glucose uptake and glycolysis, which is known as Warburg effect. In the previous issue of this journal, by using comprehensive metabolome analysis, we report that HNF1beta actually reduces and protects themselves from internal oxidative stress by dramatically changing cellular metabolism. In this article, we review the relevance and significance of cancer-specific metabolism and how they are associated with biological characteristics of OCCC via expression of HNF1beta, along with future clinical implications of targeting cancer-specific metabolism. PMID- 26375556 TI - Effect of Resident Participation on Outcomes in High-Order Cesarean Deliveries. AB - OBJECTIVE: To estimate the effect of resident participation on outcomes in women undergoing high-order cesarean deliveries. METHODS: We performed a retrospective cohort study of patients in one obstetric practice undergoing a third- or greater order cesarean delivery from 2005 to 2014. Patients with placenta previa, accreta, or failed vaginal birth after cesarean delivery were excluded. We compared outcomes between patients whose operations were performed by two attendings with patients whose operations were performed by one attending and one resident. Regression analysis was performed to control for differences at baseline. RESULTS: Three hundred seventy patients were included, 189 (51%) of whom had two attendings and 181 (49%) of whom had one attending and one resident. The mean operative time was slightly but significantly less in the two=attending group (60.9+/-17.3 compared with 62.5+/-18.3 minutes, adjusted P=.038). Otherwise, there were no significant differences in measured outcomes between the groups, including wound complications, blood loss (estimated and drop in hemoglobin), blood transfusion, major maternal morbidity (hysterectomy, cystotomy, bowel injury, intensive care unit admission, thrombosis, reoperation, death), postoperative endometritis, and postoperative days in the hospital. Among patients in the resident group, there was no difference in outcomes between cases performed by a junior (first or second year) resident compared with a senior (third or fourth year) resident. CONCLUSION: Resident participation does not negatively affect outcomes in patients undergoing high-order cesarean deliveries. Residents should be included in these complicated cases because they can obtain a significant learning experience without compromising patient safety. PMID- 26375557 TI - Development and Validation of a Laparoscopic Simulation Model for Suturing the Vaginal Cuff. AB - OBJECTIVE: To create a novel surgical simulation model for training laparoscopic suturing of the vaginal cuff and to present evidence regarding its validity as a training and assessment tool. METHODS: The three phases of this study included model construction, validity and reliability testing, and evaluation of the model as an assessment tool. The model was created using corduroy, quilt batting, and neoprene. Construct validity was determined by comparing the scores on the Global Operative Assessment of Laparoscopic Skills scale (25 points) between "expert" and "novice" groups. Experts included gynecologic surgeons (n=5) experienced in total laparoscopic hysterectomies, and novices (n=20) included gynecology trainees (postgraduate year [PGY]-2 to PGY-7). Three additional novel metrics were added to the Global Operative Laparoscopic Assessment of Laparoscopic Skills scale for a total of 40 points. The contrasting groups method was used to determine the minimum passing score. RESULTS: More than 90% of the participants "agreed" that the model resembled live surgery. Advanced novices (PGY-5 to PGY-7) performed similarly to the experts with similar median times (experts 7.3 minutes compared with advanced novices 6.3 minutes, P=.40) and total score (experts 36.5 compared with advanced novices 35.5, P=.34). In contrast, early novices (PGY-2 to PGY-4) tended to take significantly longer than experts (11.8 compared with 7.3 minutes, P<.01) and had a significantly lower total score (27 compared with 36.5, P<.01). Prior surgical experience was strongly correlated with total scores (rho=0.68). The passing total score was 32 out of 40. CONCLUSION: This novel laparoscopic surgical simulation model allows novice surgeons to practice techniques of laparoscopic suturing to achieve competence before entering the operating room. PMID- 26375558 TI - Gender Bias in Nurse Evaluations of Residents in Obstetrics and Gynecology. AB - PURPOSE: We examined the evaluations given by nurses to obstetrics and gynecology residents to estimate whether gender bias was evident. BACKGROUND: Women receive more negative feedback and evaluations than men-from both sexes. Some suggest that, to be successful in traditionally male roles such as surgeon, women must manifest a warmth-related (communal) rather than competence-related (agentic) demeanor. Compared with male residents, female residents experience more interpersonal difficulties and less help from female nurses. We examined feedback provided to residents by female nurses. METHODS: We examined Professional Associate Questionnaires (2006-2014) using a mixed-methods design. We compared scores per training year by gender using Mann-Whitney and linear regression adjusting for resident and nurse cohorts. Using grounded theory analysis, we developed a coding system for blinded comments based on principles of effective feedback, medical learners' evaluation, and impression management. chi examined the proportions of negative and positive and communal and agentic comments between genders. RESULTS: We examined 2,202 evaluations: 397 (18%) for 10 men and 1,805 (82%) for 34 women. Twenty-three compliments (eg, "Great resident!") were excluded. Evaluations per training year varied: men n=77-134; women n=384-482. Postgraduate year (PGY)-1, PGY-2, and PGY-4 women had lower mean ratings (P<.035); when adjusted, the difference remained significant in PGY-2 (MWomen=1.5+/-0.6 compared with MMen=1.7+/-0.5; P=.001). Postgraduate year-1 women received disproportionately fewer positive and more negative agentic comments than PGY-1 men (positive=17.3% compared with 40%, negative=17.3% compared with 3.3%, respectively; P=.041). CONCLUSION: Evidence of gender bias in evaluations emerged; albeit subtle, women received harsher feedback as lower level residents than men. Training in effective evaluation and gender bias management is warranted. PMID- 26375559 TI - Foreword. PMID- 26375560 TI - Comparison of risk factors for cardiovascular disease in hemodialysis and peritoneal dialysis patients. AB - OBJECTIVE: In this study, we aimed to compare the cardiovascular risk factors that might be associated with inflammation, atherosclerosis and metabolic syndrome between hemodialysis and peritoneal dialysis patients. METHODS: Fifty hemodialysis and 50 peritoneal dialysis patients who had been receiving dialysis therapy for at least one year were included in the study. Venous blood samples were taken after 12 hours of fasting, and serum glucose, triglyceride, low density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL) cholesterol, C-reactive protein, fibrinogen and homocysteine levels were measured. The presence of atherosclerotic plaques in the carotid artery was evaluated by carotid Doppler ultrasound. These data were analyzed by Student's t test, the chi-square test and the Mann-Whitney U test, as appropriate. RESULTS: No difference was found between the hemodialysis (n=50) and peritoneal dialysis (n=50) patient groups regarding mean age, gender distribution, body mass index or dialysis duration (p=0.269, 0.683, 0.426, and 0.052, respectively). LDL cholesterol, fibrinogen and homocysteine levels were significantly higher in peritoneal dialysis patients (p=0.006, 0.001, and 0.002, respectively). In patients with diabetes mellitus (n=17) who were undergoing renal replacement therapy, LDL-cholesterol and fibrinogen levels were significantly higher than in patients without diabetes mellitus who were undergoing renal replacement therapy (p=0.001 and 0.004, respectively). CONCLUSION: In our study, cardiovascular risk factors (especially LDL-cholesterol) were more frequent in peritoneal dialysis patients than in hemodialysis patients. PMID- 26375561 TI - Temporal resolution in individuals with neurological disorders. AB - OBJECTIVE: Temporal processing refers to the ability of the central auditory nervous system to encode and detect subtle changes in acoustic signals. This study aims to investigate the temporal resolution ability of individuals with mesial temporal sclerosis and to determine the sensitivity and specificity of the gaps-in-noise test in identifying this type of lesion. METHOD: This prospective study investigated differences in temporal resolution between 30 individuals with normal hearing and without neurological lesions (G1) and 16 individuals with both normal hearing and mesial temporal sclerosis (G2). Test performances were compared, and the sensitivity and specificity were calculated. RESULTS: There was no difference in gap detection thresholds between the two groups, although G1 revealed better average thresholds than G2 did. The sensitivity and specificity of the gaps-in-noise test for neurological lesions were 68% and 98%, respectively. CONCLUSIONS: Temporal resolution ability is compromised in individuals with neurological lesions caused by mesial temporal sclerosis. The gaps-in-noise test was shown to be a sensitive and specific measure of central auditory dysfunction in these patients. PMID- 26375562 TI - The impact of tracheotomy on levels of procalcitonin in patients without sepsis: a prospective study. AB - OBJECTIVE: Procalcitonin is a reliable biomarker of infection and sepsis. We aimed to determine whether tracheotomy influences the procalcitonin concentrations in patients without sepsis and assess whether operative duration and procedure affect the peak procalcitonin level. METHODS: A total of 38 non septic patients who required a tracheotomy underwent either a percutaneous dilatational tracheotomy (n=19) or a surgical tracheotomy (n=19). Procalcitonin levels were measured at the beginning of the tracheotomy and at 2 h, 4 h, 8 h, 24 h, 48 h and 72 h after the procedure. RESULTS: The baseline procalcitonin concentration before the tracheotomy was 0.24 +/- 0.13 ng/mL. The postoperative levels increased rapidly, with a 4-fold elevation after 2 h, reaching a peak 4 h later with a 5-fold increase over baseline. Thereafter, the levels gradually returned to 2-fold greater than the baseline level within 72 h. The peak levels of procalcitonin showed a significant positive correlation with operative durations (r=0.710, p<0.001) and procedures (rho=0.670, p<0.001). CONCLUSION: In patients without sepsis, tracheotomy induces a rapid release of serum procalcitonin, and the operative duration and procedure have significant impacts on the peak procalcitonin levels. Thus, the nonspecific increase in procalcitonin levels following tracheotomy needs to be considered when this measure is used to evaluate infection. PMID- 26375563 TI - Differences between the real and the desired worlds in the results of clinical trials. AB - OBJECTIVE: We refer to the effectiveness (known as pragmatic or real world) and efficacy (known as explanatory or desired or ideal world) of interventions. However, these terms seem to be randomly chosen by investigators who design clinical trials and do not always reflect the true purpose of the study. A pragmatic-explanatory continuum indicator summary tool was thus developed with the aim of identifying the characteristics of clinical trials that distinguish between effectiveness and efficacy issues. We verified whether clinical trials used the criteria proposed by the indicator summary tool, and we categorized these clinical trials according to a new classification. METHOD: A systematic survey of randomized clinical trials was performed. We added a score ranging from 0 (more efficacious) to 10 (more effective) to each domain of the indicator summary tool and proposed the following classifications: high efficacy (<25), moderate efficacy (25-50), moderate effectiveness (51-75), and high effectiveness (<75). RESULTS: A total of 844 randomized trials were analyzed. No analyzed trials used the criteria proposed by the indicator summary tool. Approximately 44% of the trials were classified as having moderate effectiveness, and 43.82% were classified as having moderate efficacy. CONCLUSIONS: Most clinical trials used the term "efficacy" to illustrate the application of results in clinical practice, but the majority of those were classified as having moderate effectiveness according to our proposed score. The classification based on the 0 100 score is still highly subjective and can be easily misunderstood in all domains based on each investigator's own experiences and knowledge. PMID- 26375564 TI - The impact of a discrepancy between actual and preferred living arrangements on life satisfaction among the elderly in China. AB - OBJECTIVES: To explore the effects of a discrepancy between actual and preferred living arrangements on the relationship between living arrangements and life satisfaction among the elderly in China. METHODS: Secondary analysis of the 2005 dataset of the Chinese Longitudinal Healthy Longevity Survey was performed. A binary logistic regression model was used to analyze the relationship between life satisfaction and living arrangements. RESULTS: Among those with concordant actual and preferred living arrangements, living in a nursing home increased the likelihood of life satisfaction, whereas living alone and living with a spouse decreased the likelihood of life satisfaction compared to living with the next generation and a spouse. Among those with discordant living arrangements, there were no differences in life satisfaction between the various living arrangements, except that living with a spouse increased life satisfaction compared to living with the next generation and a spouse. CONCLUSIONS: A discrepancy between actual and preferred living arrangements modifies the relationship between life satisfaction and actual living arrangement. Living in a nursing home is a good option for Chinese elder care only if the older individual emotionally accepts it. Living alone or with a spouse is not a good arrangement for elder care, even though it is often preferred by the elderly. Those with discordant living arrangements are more satisfied living with their spouses. PMID- 26375565 TI - Serum bilirubin value predicts hospital admission in carbon monoxide-poisoned patients. Active player or simple bystander? AB - OBJECTIVES: Although carbon monoxide poisoning is a major medical emergency, the armamentarium of recognized prognostic biomarkers displays unsatisfactory diagnostic performance for predicting cumulative endpoints. METHODS: We performed a retrospective and observational study to identify all patients admitted for carbon monoxide poisoning during a 2-year period. Complete demographical and clinical information, along with the laboratory data regarding arterial carboxyhemoglobin, hemoglobin, blood lactate and total serum bilirubin, was retrieved. RESULTS: The study population consisted of 38 poisoned patients (23 females and 15 males; mean age 39 +/- 21 years). Compared with discharged subjects, hospitalized patients displayed significantly higher values for blood lactate and total serum bilirubin, whereas arterial carboxyhemoglobin and hemoglobin did not differ. In a univariate analysis, hospitalization was significantly associated with blood lactate and total serum bilirubin, but not with age, sex, hemoglobin or carboxyhemoglobin. The diagnostic performance obtained after combining the blood lactate and total serum bilirubin results (area under the curve, 0.90; 95% CI, 0.81-0.99; p<0.001) was better than that obtained for either parameter alone. CONCLUSION: Although it remains unclear whether total serum bilirubin acts as an active player or a bystander, we conclude that the systematic assessment of bilirubin may, alongside lactate levels, provide useful information for clinical decision making regarding carbon monoxide poisoning. PMID- 26375566 TI - Influence of hyperprolactinemia on collagen fibers in the lacrimal gland of female mice. AB - OBJECTIVE: To quantify the collagen fibers in the lacrimal gland of female mice with hyperprolactinemia. METHODS: Forty adult female mice were randomly divided into two groups with 20 animals each: nonpregnant control (CTR1, control group, 0.2 mL of saline solution) and nonpregnant experimental (HPRL1, experimental group, 200 ug/day metoclopramide). Treatments lasted for 50 consecutive days. On day 50, 10 females from each group (control and experimental) were euthanized in the proestrus phase; then, the blood was collected and the lacrimal glands were removed. Thereafter, the remaining females were placed with the mates and continued to receive treatment with saline solution or metoclopramide. On the 6th post-coital day, 10 pregnant females from the control group (CTR2) and 10 pregnant females from the experimental group (HPRL2) were euthanized, after which blood was collected and the lacrimal glands removed. The lacrimal glands were processed for morphological analyses and collagen quantification, and prolactin and sex steroid levels were measured in the blood samples. Data were statistically analyzed using an unpaired Student t test (p<0.05). RESULTS: Morphological analysis revealed greater structural tissue disorganization of the lacrimal glands in the metoclopramide-treated groups. The total collagen content was significantly higher in the HPRL1 group than in the CTR1 group (p<0.05), whereas the difference between the CTR2 and HPRL2 groups was not significant. CONCLUSION: Our data suggest an impairment in the functioning of the lacrimal gland as a consequence of increased prolactin levels and decreased serum levels of estrogen and progesterone. PMID- 26375567 TI - Driving evaluation methods for able-bodied persons and individuals with lower extremity disabilities: a review of assessment modalities. AB - Assessing the driving abilities of individuals with disabilities is often a very challenging task because each medical condition is accompanied by physical impairments and because relative individual functional performance may vary depending on personal characteristics.We identified existing driving evaluation modalities for able-bodied and lower extremity-impaired subjects (spinal cord injury patients and amputees) and evaluated the potential relationships between driving performance and the motor component of driving.An extensive scoping review of the literature was conducted to identify driving assessment tools that are currently used for able-bodied individuals and for those with spinal cord injury or lower extremity amputation. The literature search focused on the assessment of the motor component of driving. References were electronically obtained via Medline from the PubMed, Ovid, Web of Science and Google Scholar databases.This article compares the current assessments of driving performance for those with lower extremity impairments with the assessments used for able bodied persons. Very few articles were found concerning "Lower Extremity Disabilities," thus confirming the need for further studies that can provide evidence and guidance for such assessments in the future. Little is known about the motor component of driving and its association with the other driving domains, such as vision and cognition. The available research demonstrates the need for a more evidenced-based understanding of how to best evaluate persons with lower extremity impairment. PMID- 26375568 TI - Analgesia for total knee arthroplasty: a meta-analysis comparing local infiltration and femoral nerve block. AB - Patients frequently experience postoperative pain after a total knee arthroplasty; such pain is always challenging to treat and may delay the patient's recovery. It is unclear whether local infiltration or a femoral nerve block offers a better analgesic effect after total knee arthroplasty.We performed a systematic review and meta-analysis of randomized controlled trials to compare local infiltration with a femoral nerve block in patients who underwent a primary unilateral total knee arthroplasty. We searched Pubmed, EMBASE, and the Cochrane Library through December 2014. Two reviewers scanned abstracts and extracted data. The data collected included numeric rating scale values for pain at rest and pain upon movement and opioid consumption in the first 24 hours. Mean differences with 95% confidence intervals were calculated for each end point. A sensitivity analysis was conducted to evaluate potential sources of heterogeneity.While the numeric rating scale values for pain upon movement (MD 0.62; 95%CI: -1.13 to -0.12; p=0.02) in the first 24 hours differed significantly between the patients who received local infiltration and those who received a femoral nerve block, there were no differences in the numeric rating scale results for pain at rest (MD-0.42; 95%CI:-1.32 to 0.47; p=0.35) or opioid consumption (MD 2.92; 95%CI:-1.32 to 7.16; p=0.18) in the first 24 hours.Local infiltration and femoral nerve block showed no significant differences in pain intensity at rest or opioid consumption after total knee arthroplasty, but the femoral nerve block was associated with reduced pain upon movement. PMID- 26375569 TI - Partial epilepsy: A pictorial review of 3 TESLA magnetic resonance imaging features. AB - Epilepsy is a disease with serious consequences for patients and society. In many cases seizures are sufficiently disabling to justify surgical evaluation. In this context, Magnetic Resonance Imaging (MRI) is one of the most valuable tools for the preoperative localization of epileptogenic foci. Because these lesions show a large variety of presentations (including subtle imaging characteristics), their analysis requires careful and systematic interpretation of MRI data. Several studies have shown that 3 Tesla (T) MRI provides a better image quality than 1.5 T MRI regarding the detection and characterization of structural lesions, indicating that high-field-strength imaging should be considered for patients with intractable epilepsy who might benefit from surgery. Likewise, advanced MRI postprocessing and quantitative analysis techniques such as thickness and volume measurements of cortical gray matter have emerged and in the near future, these techniques will routinely enable more precise evaluations of such patients. Finally, the familiarity with radiologic findings of the potential epileptogenic substrates in association with combined use of higher field strengths (3 T, 7 T, and greater) and new quantitative analytical post-processing techniques will lead to improvements regarding the clinical imaging of these patients. We present a pictorial review of the major pathologies related to partial epilepsy, highlighting the key findings of 3 T MRI. PMID- 26375570 TI - Pedagogical strategies to teach bachelor students evidence-based practice: A systematic review. AB - AIM: The aim of this study is to review international scientific articles about pedagogical strategies to teach nursing students at bachelor degree evidence based practice (EBP). METHOD: A literature review including peer reviewed, original, empirical articles describing pedagogical interventions aimed at teaching bachelor's degree nursing students EBP in the period 2004-2014. Theories of discretion, knowledge transfer and cognitive maturity development are used as analytical perspectives. RESULTS: The main challenge teaching evidence based practice is that the students fail to see how research findings contribute to nursing practice. The pedagogical strategies described are student active learning methods to teach the students information literacy and research topics. Information literacy is mainly taught according to the stages of EBP. These stages focus on how to elaborate evidence from research findings for implementation into nursing practice. The articles reviewed mainly use qualitative, descriptive designs and formative evaluations of the pedagogical interventions. CONCLUSION: Although a considerable effort in teaching information literacy and research topics, nursing students still struggle to see the relevance evidence for nursing practice. Before being introduced to information literacy and research topics, students need insight into knowledge transfer and their own epistemic assumptions. Knowledge transfer related to clinical problems should be the learning situations prioritized when teaching EBP at bachelor level. Theoretical perspectives of cognitive maturity development, knowledge transfer and discretion in professional practice give alternative ways of designing pedagogical strategies for EBP. More research is needed to develop and test pedagogical strategies for EBP in light of these theories. PMID- 26375571 TI - Homemade Firearm Suicide With Dumbbell Pipe Triggering by an Air-Compressed Gun: Case Report and Review of Literature. AB - Firearm suicides are frequent and well described in the forensic literature, particularly in Europe and the United States. However, the use of homemade and improvised firearms is less well described. The present case reports a suicide with an original improvised gun created using an air-compressed pellet gun and a dumbbell pipe. The aims of this study were to describe the scene, the external examination of the corpse, the body scan, and the autopsy; to understand the mechanism of death; and to compare the results with a review of the forensic literature to highlight the epidemiology of homemade firearm use, the tools used for homemade and improvised firearms in suicides versus homicides, and the manners in which homemade firearms are used (homicide or suicide, particularly in complex suicide cases). PMID- 26375573 TI - Puffed and bothered: Personality, performance, and the effects of stress on checkered pufferfish. AB - Although consistent individual-level differences in behaviour are widespread and potentially important in evolutionary and ecological processes, relatively few studies focus on the physiological mechanisms that might underlie and regulate these individual-level differences in wild populations. We conducted experiments to determine whether checkered pufferfish (Sphoeroides testudineus), which were collected from a dynamic (in terms of depth and water temperature) tidal mangrove creek environment in The Bahamas, have consistent individual-level differences in locomotor activity and the response to a simulated predator threat, as well as swimming performance and puffing in response to stressors. The relationships between personality and performance traits were evaluated to determine whether they represented stress-coping styles or syndromes. Subsequently, a displacement study was conducted to determine how personality and performance in the laboratory compared to movements in the field. In addition, we tested whether a physiological dose of the stress hormone cortisol would alter individual consistency in behavioural and performance traits. We found that pufferfish exhibited consistent individual differences in personality traits over time (e.g., activity and the duration of a response to a threat) and that performance was consistent between the lab and the natural enclosure. Locomotor activity and the duration of startled behaviour were not associated with swimming and puffing performance. Locomotor activity, puffing performance, and swimming performance were not related to whether fish returned to the tidal creek of capture after displacement. Similarly, a cortisol treatment did not modify behaviour or performance in the laboratory. The results reveal that consistent individual level differences in behaviour and performance were present in a population from a fluctuating and physiologically challenging environment but that such traits are not necessarily correlated. We also determined that certain individual performance traits were repeatable between the lab and a natural enclosure. However, we found no evidence of a relationship between exogenous cortisol levels and behavioural traits or performance in these fish, which suggests that other internal and external mechanisms may underlie the behaviours and performance tested. PMID- 26375575 TI - An Alternative Approach to Evaluate the Wettability of Carbon Fiber Substrates. AB - The wettability of carbon fiber substrate plays an important role in a vast number of electrochemical energy production and storage technologies. Here, we report an alternative approach to evaluate the relative wettability for three substrates with the solid-liquid (S-L) interfacial area as the wettability parameter. We applied electrochemical techniques to quantify the S-L interfacial area and obtained the relative wettability on for three substrates with varying fiber morphology. This work proposes and validates a methodology to experimentally measure the substrate wettability and elucidates important aspects of the relevant wetting phenomena. Our results indicate that the wettability of carbon fiber substrate is affected by the liquid intrusion resulting from the instability of the Cassie-Baxter wetting state and that the contact angle is not dependent on the S-L interfacial area under the droplet. The present technique can be used to characterize the surface wettability of a wide range of conductive surfaces with irregular and multiscale surface roughness features. PMID- 26375574 TI - Prevailing Sydney like Norovirus GII.4 VLPs induce systemic and mucosal immune responses in mice. AB - The newly emerged Norovirus (NoV) Sydney 2012 strain has been sweeping all over the world, causing acute non-bacterial gastroenteritis in adults and children. Due to a lack of cell culture system, virus like particles (VLPs) has been assembled and used as vaccine candidates in preclinical and clinical studies. Expression of the major capsid protein of NoVs using recombinant baculovirus expression system in Sf9 cells leads to formation of VLPs that are morphologically and antigenically similar to true virions. In this study, VLPs were successfully produced using the VP1 of Sydney-2012-like strain and its immunogenicity was evaluated by different routes and its capability in inducing mucosal immune responses in the presence and absence of adjuvants in BALB/c mice. Administration of NoV VLPs in the presence of Al(OH)3 or monophosphoryl lipid A (MPL-A) led to high titers of VLP-specific IgG antibodies. Administration of VLPs orally in the presence of cholera toxin subunit B (CTB) didn't enhance mucosal immune response as less fecal IgA positive mice were observed when compared with those given VLPs only. Our study represents the first immunogenicity study of VLPs derived from current pandemic Sydney 2012 strain and which might have implications in the development of NoVs vaccine in china. PMID- 26375576 TI - Surface Emitting, High Efficiency Near-Vacuum Ultraviolet Light Source with Aluminum Nitride Nanowires Monolithically Grown on Silicon. AB - To date, it has remained challenging to realize electrically injected light sources in the vacuum ultraviolet wavelength range (~200 nm or shorter), which are important for a broad range of applications, including sensing, surface treatment, and photochemical analysis. In this Letter, we have demonstrated such a light source with molecular beam epitaxially grown aluminum nitride (AlN) nanowires on low cost, large area Si substrate. Detailed angle dependent electroluminescence studies suggest that, albeit the light is TM polarized, the dominant light emission direction is from the nanowire top surface, that is, along the c axis, due to the strong light scattering effect. Such an efficient surface emitting device was not previously possible using conventional c-plane AlN planar structures. The AlN nanowire LEDs exhibit an extremely large electrical efficiency (>85%), which is nearly ten times higher than the previously reported AlN planar devices. Our detailed studies further suggest that the performance of AlN nanowire LEDs is predominantly limited by electron overflow. This study provides important insight on the fundamental emission characteristics of AlN nanowire LEDs and also offers a viable path to realize an efficient surface emitting near-vacuum ultraviolet light source through direct electrical injection. PMID- 26375578 TI - Diagnostic Experiences of Children With Attention-Deficit/Hyperactivity Disorder. AB - OBJECTIVES: This report describes the diagnostic experiences of a sample of children in the United States diagnosed with attention-deficit/hyperactivity disorder (ADHD) as of 2011-2012. DATA SOURCES: Data were drawn from the 2014 National Survey of the Diagnosis and Treatment of Attention-Deficit/Hyperactivity Disorder and Tourette Syndrome, a follow-up to the 2011-2012 National Survey of Children's Health. RESULTS: The median age at which children with ADHD were first diagnosed with the disorder was 7 years; one-third were diagnosed before age 6. Children with ADHD were diagnosed by a wide variety of health care providers, including primary care physicians and specialists. Regardless of age at diagnosis, the majority of children (53.1%) were first diagnosed by primary care physicians. Notable differences were found by age at diagnosis for two types of specialists. Children diagnosed before age 6 were more likely to have been diagnosed by a psychiatrist, and those diagnosed at ages 6 and over were more likely to have been diagnosed by a psychologist. Among children diagnosed with ADHD, the initial concern about a child's behavior was most commonly expressed by a family member (64.7%), but someone from school or daycare first expressed concern for about one-third of children later diagnosed with ADHD (30.1%). For approximately one out of five children (18.1%), only family members provided information to the child's doctor during the ADHD assessment. PMID- 26375577 TI - Significance of the Extent of Intestinal Resection on the Outcome of a Short bowel Syndrome in a Porcine Model. AB - AIM OF THE STUDY: Insufficient data are available to determine the most suitable extent of intestinal resection required to induce short-bowel syndrome (SBS) in pigs. This study aimed to compare the three main SBS-models published. METHODS: A 75%, 90%, or 100% mid-intestinal resection was performed in groups of n = 5 pigs each. Clinical (body weight, stool consistency) and biochemical (serum eletrolytes, citrulline, albumin, prealbumin, and transferrin) parameters were determined daily, functional (D-xylose resorption) and histological (intestinal villus length) parameters were determined after 2 weeks. A t-test and ANOVA were used for statistical analysis. RESULTS: Only in the 100% group, we observed a persistent weight loss (13.6 +/- 3.8%) and diarrhea, as well as a decrease in prealbumin-levels (41%) and transferrin levels (33%). Serum electrolytes remained stable in all groups during the observation period. Citrulline stabilized at different levels (100% group 13.9 +/- 1.0 MUmol/L; 90% group 18.8 +/- 1.0 MUmol/L; 75% group 26.3 +/- 1.4 MUmol/L; all p < .05). D-xylose resorption was lowest in the 100%, followed by 90% and 75% group (100% group 32.8 +/- 4.9 mg/L; 90% group 50.0 +/- 19.6 mg/L; 75% group 57.8 +/- 8.8 mg/L; p = .393). Intestinal villus length decreased in all groups (100% group 11.0%; 90% group 14.0%; 75% group 19.1%). CONCLUSIONS: 75% intestinal resection is less suitable as an SBS model, as animals tend to recover remarkably. The 90% model is suitable for longer-term studies, as animals might survive longer due to partial compensation. Due to severe nutritional, biochemical, and physiological derangements, the 100% model can only be used for acute experiments and those immediately followed by small bowel transplantation. PMID- 26375579 TI - Nonviral Plasmid DNA Carriers Based on N,N'-Dimethylaminoethyl Methacrylate and Di(ethylene glycol) Methyl Ether Methacrylate Star Copolymers. AB - Star polymers with random and block copolymer arms made of cationic N,N' dimethylaminoethyl methacrylate (DMAEMA) and nonionic di(ethylene glycol) methyl ether methacrylate (DEGMA) were synthesized via atom transfer radical polymerization (ATRP) and used for the delivery of plasmid DNA in gene therapy. All stars were able to form polyplexes with plasmid DNA. The structure and size of the polyplexes were precisely determined using light scattering and cryo-TEM microscopy. The hydrodynamic radius of a complex of DNA with star was dependent on the architecture of the star arms, the DEGMA content and the number of amino groups in the star compared to the number of phosphate groups of the nucleic acid (N/P ratio). The smallest polyplexes (Rh90 degrees ~50 nm) with positive zeta potentials (~15 mV) were formed of stars with N/P=6. The introduction of DEGMA into the star structure caused a decrease of polyplex cytotoxicity in comparison to DMAEMA homopolymer stars. The overall transfection efficiency using HT-1080 cells showed that the studied systems are prospective gene delivery agents. The most promising results were obtained for stars with random copolymer arms of high DEGMA content. PMID- 26375580 TI - Assessment of biomarkers in type 2 diabetic subjects without any complications. AB - BACKGROUND: Type 2-diabetes (T2D), is a public health problem which has reached epidemic proportions due to the rapidly increasing rates of this disease worldwide. It is known that adipose tissue can synthesize and release pro inflammatory cytokines, tumor necrosis factor-alpha, interleukin-1, adiponectin and leptin that are associated with body fat mass. Hence comparing the biomarkers with individuals without hyperglycemia would help us to understand the level of increase in their values though the vascular complications have not begun. MATERIALS AND METHODS: This was a cross sectional study comprising 229 diabetic persons and 205 healthy individuals. High sensitivity reactive protein (hs-CRP) was estimated using nephelometry technique. Inflammatory markers and adiponectin were measured using ELISA instrument. RESULTS: Tumor necrosis factor alpha (TNF alpha) (40.56%) and Leptin (45.43%) were significantly increased in the diabetic group when compared with normal study population. Adiponectin was significantly decreased in diabetic study population (11.94%). This was supported by a significant correlation between the glycemic index HbA1c and TNF-alpha (r=0.376, p=0.01), adiponectin (r=-0.381, p=0.01) and leptin (r=0.269, p=0.01) in diabetic population, but the significance was lost among the normal healthy individuals. CONCLUSIONS: The most promising biomarkers of diabetes such as TNF-alpha, adiponectin, leptin has shown a marked difference in this diabetic population. This study proves the assessment of these biomarkers as future predictors of type 2 diabetes. PMID- 26375581 TI - Twitter Language Use Reflects Psychological Differences between Democrats and Republicans. AB - Previous research has shown that political leanings correlate with various psychological factors. While surveys and experiments provide a rich source of information for political psychology, data from social networks can offer more naturalistic and robust material for analysis. This research investigates psychological differences between individuals of different political orientations on a social networking platform, Twitter. Based on previous findings, we hypothesized that the language used by liberals emphasizes their perception of uniqueness, contains more swear words, more anxiety-related words and more feeling-related words than conservatives' language. Conversely, we predicted that the language of conservatives emphasizes group membership and contains more references to achievement and religion than liberals' language. We analysed Twitter timelines of 5,373 followers of three Twitter accounts of the American Democratic and 5,386 followers of three accounts of the Republican parties' Congressional Organizations. The results support most of the predictions and previous findings, confirming that Twitter behaviour offers valid insights to offline behaviour. PMID- 26375582 TI - Chorioamnionitis and Patent Ductus Arteriosus: A Systematic Review and Meta Analysis. AB - BACKGROUND: Chorioamnionitis has recently been reported as a risk factor for various neonatal diseases, including cerebral palsy, bronchopulmonary dysplasia, and necrotizing enterocolitis, but its effect on patent ductus arteriosus (PDA) is unclear. We performed a systematic review and meta-analysis to evaluate the effect of chorioamnionitis on PDA. METHODS: We searched PubMed, EMBASE, Cochrane Library, and KoreaMed databases using the terms: "intrauterine infection" or "maternal infection" or "antenatal infection" or "chorioamnionitis" or "placenta inflammation" or "placenta pathology" or "neonatal outcome" or "neonatal morbidity" or "PDA or patent ductus arteriosus" or "ductus arteriosus," and "prematurity" or "very low birth weight infant." Studies were included if they were randomized controlled trials, case-control studies, or cohort studies that included information relating to chorioamnionitis and PDA. RESULTS: Among 1,571 studies, a total of 23 studies (17,708 cases) were included in the meta-analysis to analyze the relationship between chorioamnionitis and PDA, except one study that only included PDA requiring surgical ligation. The association between chorioamnionitis and PDA was statistically significant (odds ratio [OR] 1.43; 95% confidence interval [CI] 1.19, 1.72; P < 0.0001). In subgroup analysis, clinical chorioamnionitis was not associated with PDA (OR 1.28; 95% CI 1.00, 1.64, 1.790; P = 0.05), whereas histologic chorioamnionitis (OR 1.54; 95% CI 1.10, 2.15; P = 0.01) and chorioamnionitis diagnosed from both clinical and histologic findings (OR 1.75; 95% CI 1.07, 2.86; P = 0.03) showed significant associations with PDA. Chorioamnionitis did not increase the risk of PDA requiring surgical ligation (OR 1.23; 95% CI 0.69, 2.17; P = 0.48), and antenatal steroid use reduced the risk of PDA (OR 0.62; 95% CI 0.42, 0.90; P = 0.01) after chorioamnionitis. CONCLUSIONS: The results from this meta-analysis support an association between maternal chorioamnionitis and PDA in offspring. PMID- 26375583 TI - Asymmetric Multicomponent Sulfa-Michael/Mannich Cascade Reaction: Synthetic Access to 1,2-Diamino-3-Organosulfur Compounds and 2-Nitro Allylic Amines. AB - A novel catalytic asymmetric three-component intermolecular sulfa-Michael/Mannich cascade reaction has been developed using a chiral multifunctional catalyst. This reaction provides facile access to 1-amino-2-nitro-3-organosulfur compounds bearing three consecutive stereocenters in high yields (up to 96%) with good diastereo- (up to 91:4:4:1 dr) and excellent enantioselectivities (93-99% ee). Furthermore, the products of this reaction could be facilely transformed into potentially bioactive 1, 2-diamino-3-organosulfur compounds and 2-nitro allylic amines. PMID- 26375584 TI - Discovery of the First Selective, Nonpeptidic Orexin 2 Receptor Agonists. AB - In this issue, Nagase and colleagues report the discovery of the first selective nonpeptidic orexin 2 receptor (OX2R) agonists. The discovery of these OX2R selective agonists opens up new avenues for therapies related to the activation of the orexin system, especially with respect to the treatment of sleep disorders such as narcolepsy. PMID- 26375585 TI - The Role of Necroptosis in Burn Injury Progression in a Rat Comb Burn Model. AB - OBJECTIVES: Progression of cell death after burn injury may occur by one of three mechanisms: passive necrosis, apoptosis, and programmed necroptosis that requires the receptor-interacting protein kinase-3 (RIP-3). The hypothesis was that RIP-3 is present in normal and burned skin; that necroptosis plays a role in burn injury progression; and that treatment with necrostatin-1, an inhibitor of necroptosis, would reduce burn progression. METHODS: Skin specimens from rats were examined for the presence of RIP-3. Using a 150-g brass comb preheated to 100 degrees C, we created two comb burns (one on each side) consisting of four rectangular burns, separated by three unburned interspaces, on both sides of the backs of anesthetized male Sprague-Dawley rats (240 to 300 g). The interspaces represent the ischemic zones surrounding the central necrotic core. Left untreated, these areas undergo necrosis. In the first experiment, 10 rats each were randomized to 1.65 mg/kg necrostatin-1 or control given by intraperitoneal injection 1 hour after injury. In the second experiment, 10 rats each were randomized to two intravenous injections of 1.65 mg/kg necrostatin-1 or its vehicle at 1 and 4 hours after injury. The primary outcome was the percentage of interspaces undergoing necrosis within 7 days of injury. Binary data were compared with chi-square or Fishers' exact tests. RESULTS: All normal and burned skin specimens from rats stained positive for RIP-3. In the first experiment, nearly all unburned interspaces in both the experimental and the control rats underwent necrosis (47 of 48, 97.9% vs. 48 of 48, 100%; p = not significant [NS]). Similarly, in the second experiment, there was no difference in the percentage of unburned interspaces undergoing necrosis within 7 days of injury in rats treated with two doses of necrostatin-1 or the control vehicle (46 of 48, 95.8% vs. 48 of 48, 100%; p = NS). There were no wound infections noted in rats injected with necrostatin-1. CONCLUSIONS: The skin of rats contains RIP-3 necessary for necroptosis. Injection of rats with either a single intraperitoneal dose or two intravenous doses of necrostatin-1 failed to reduce burn injury progression in a rat comb burn model. This may be due to inactivity of necrostatin-1 or the lack of a role of necroptosis in burn injury progression in the rat comb burn model. PMID- 26375586 TI - Ghrelin Gene Variants Influence on Metabolic Syndrome Components in Aged Spanish Population. AB - BACKGROUND: The role of genetic variations within the ghrelin gene on cardiometabolic profile and nutritional status is still not clear in humans, particularly in elderly people. OBJECTIVES: We investigated six SNPs of the ghrelin gene and their relationship with metabolic syndrome (MS) components. SUBJECTS AND METHODS: 824 subjects (413 men/411 women, age 77.31+/-5.04) participating in the Mataro aging study (n = 310) and the Hortega study (n = 514) were analyzed. Anthropometric variables, ghrelin, lipids, glucose and blood pressure levels were measured, and distribution of SNPs -994CT (rs26312), -604GA (rs27647), -501AC (rs26802), R51Q (rs34911341), M72L (rs696217) and L90G (rs4684677) of the ghrelin gene evaluated. Genotypes were determined by multiplex PCR and SNaPshot minisequencing. MS (IDF criteria) was found in 54.9%. RESULTS: No association between any of the SNPs and levels of total fasting circulating ghrelin levels was found. C/A-A/A genotype of M72L was associated with increased risk of central obesity according to IDF criteria, while G/A-G/G genotypes of 604GA with reduced risk. A/A genotype of -501AC polymorphism was associated to decreased BMI. In relation to lipid profile, the same genotypes of -604GA were associated with increased total cholesterol and LDL-cholesterol and -501AC with reduced triglycerides. There were no associations with systolic or diastolic blood pressure levels or with hypertension, glucose levels or diabetes and ghrelin polymorphisms. However, G/G genotype of -604GA was associated with glucose >100 mg/dL. Haplotype analysis showed that only one haplotype is associated with increased risk of waist circumference and central obesity. The analysis of subjects by gender showed an important and different association of these polymorphisms regarding MS parameters. CONCLUSION: Ghrelin gene variants 604GA, -501AC and M72L are associated with certain components of MS, in particular to BMI and lipid profile in elderly Spanish subjects. PMID- 26375587 TI - Mitochondrial Profiling of Acute Myeloid Leukemia in the Assessment of Response to Apoptosis Modulating Drugs. AB - BH3 profiling measures the propensity of transformed cells to undergo intrinsic apoptosis and is determined by exposing cells to BH3-mimicking peptides. We hypothesized that basal levels of prosurvival BCL-2 family proteins may modulate the predictive power of BH3 profiling and termed it mitochondrial profiling. We investigated the correlation between cell sensitivity to apoptogenic agents and mitochondrial profiling, using a panel of acute myeloid leukemias induced to undergo apoptosis by exposure to cytarabine, the BH3 mimetic ABT-199, the MDM2 inhibitor Nutlin-3a, or the CRM1 inhibitor KPT-330. We found that the apoptogenic efficacies of ABT-199 and cytarabine correlated well with BH3 profiling reflecting BCL2, but not BCL-XL or MCL-1 dependence. Baseline BCL-2 protein expression analysis increased the ability of BH3 profiling to predict resistance mediated by MCL-1. By utilizing engineered cells with overexpression or knockdown of BCL-2 family proteins, Ara-C was found to be independent, while ABT-199 was dependent on BCL-XL. BCL-2 and BCL-XL overexpression mediated resistance to KPT 330 which was not reflected in the BH3 profiling assay, or in baseline BCL-2 protein levels. In conclusion, mitochondrial profiling, the combination of BH3 profiling and prosurvival BCL-2 family protein analysis, represents an improved approach to predict efficacy of diverse agents in AML and may have utility in the design of more effective drug combinations. PMID- 26375589 TI - Cost and Utility Analysis of a Store-and-Forward Teledermatology Referral System: A Randomized Clinical Trial. AB - Importance: The costs and utility of teledermatology are important features of implementation. Such an analysis requires a description of the perspective of the entity that will bear the cost. Objective: To assess the costs and utility of a store-and-forward teledermatology referral process compared with a conventional referral process from the perspectives of the Department of Veterans Affairs (VA) and society. Design, Setting, and Participants: Three hundred ninety-one randomized participants were referred from remote sites of primary care to the dermatology services of 2 VA medical facilities for ambulatory skin conditions from December 2008 through June 2010, and follow-up was completed in March 2011. The time trade-off utility measures and costs were collected during a 9-month period among participants in a 2-site parallel group randomized clinical trial. The perspectives of the VA and society were evaluated. The multiple imputation procedure or weighted means were used for missing data elements. Data were analyzed from January to July 2014. Interventions: Referrals were managed using store-and-forward teledermatology or a conventional text-based referral process. Main Outcomes and Measures: Total costs from the perspectives of the VA and society incurred during the 9-month follow-up were used to derive per-participant costs. Utility, using the time trade-off method, was the measure of effectiveness. Results: From the VA perspective, the total cost for conventional referrals was $66 145 (minimum, $58 697; maximum, $71 635), or $338 (SD, $291) per participant (196 participants); the total cost for teledermatology referrals was $59 917 (mimimum, $51 794; maximum, $70 398), or $308 (SD, $298) per participant (195 participants). The $30 difference in per-participant cost was not statistically significant (95% CI, -$79 to $20). From the societal perspective, the total cost for conventional referrals was $106 194 (minimum, $98 746; maximum, $111 684), or $542 (SD, $403) per participant (196 participants); the total cost for teledermatology referrals was $89 523 (minimum, $81 400; maximum, $100 400) or $460 (SD, $428) per participant. This $82 difference in per participant cost was statistically significant (95% CI, -$12 to -$152). From baseline to the 9-month follow-up, the time trade-off utility value improved by 0.02 in the conventional referral group and 0.03 in the teledermatology group. This difference was not statistically significant (P = .50). Conclusions and Relevance: Compared with conventional referrals, store-and-forward teledermatology referrals were performed at a comparable cost (VA perspective) or at a lower cost (societal perspective) with no evidence of a difference in utility as measured by the time trade-off method. Trial Registration: clinicaltrials.gov Identifier: NCT00488293. PMID- 26375588 TI - Disruption of Type I Interferon Induction by HIV Infection of T Cells. AB - Our main objective of this study was to determine how Human Immunodeficiency Virus (HIV) avoids induction of the antiviral Type I Interferon (IFN) system. To limit viral infection, the innate immune system produces important antiviral cytokines such as the IFN. IFN set up a critical roadblock to virus infection by limiting further replication of a virus. Usually, IFN production is induced by the recognition of viral nucleic acids by innate immune receptors and subsequent downstream signaling. However, the importance of IFN in the defense against viruses has lead most pathogenic viruses to evolve strategies to inhibit host IFN induction or responses allowing for increased pathogenicity and persistence of the virus. While the adaptive immune responses to HIV infection have been extensively studied, less is known about the balance between induction and inhibition of innate immune defenses, including the antiviral IFN response, by HIV infection. Here we show that HIV infection of T cells does not induce significant IFN production even IFN I Interferon production. To explain this paradox, we screened HIV proteins and found that two HIV encoded proteins, Vpu and Nef, strongly antagonize IFN induction, with expression of these proteins leading to loss of expression of the innate immune viral RNA sensing adaptor protein, IPS-1 (IFN-beta promoter stimulator-1). We hypothesize that with lower levels of IPS-1 present, infected cells are defective in mounting antiviral responses allowing HIV to replicate without the normal antiviral actions of the host IFN response. Using cell lines as well as primary human derived cells, we show that HIV targeting of IPS-1 is key to limiting IFN induction. These findings describe how HIV infection modulates IFN induction providing insight into the mechanisms by which HIV establishes infection and persistence in a host. PMID- 26375590 TI - Second-Line Treatment of Her2-Positive Metastatic Breast Cancer: Trastuzumab beyond Progression or Lapatinib? A Population Based Cohort Study. AB - BACKGROUND: The relative efficacy of lapatinib vs. continuing trastuzumab beyond progression (TBP) in HER2-positive metastatic breast cancer (MBC) patients, who progressed on first-line trastuzumab, is still unclear. The objective of this population based cohort study was to compare outcomes of lapatinib vs. TBP in daily practice. METHODS: All HER2-positive MBC patients who began second-line anti HER2 therapy between 1st January 2010 and 30th August 2013 were selected from Clalit Health Services' (CHS) electronic database. Available data on patient and disease characteristics and treatments were analyzed. The primary endpoint was overall survival (OS). Outcomes were compared using the Kaplan-Meier (log rank) method and Cox proportional hazards model. RESULTS: 64 patients received second-line lapatinib and 93 TBP. The two treatment groups were similar in age and co-morbidity rates, but differed in proportion of prior adjuvant trastuzumab (lapatinib: 29.7%, TBP: 16.1%, P = 0.043) and rates of prior brain metastases (lapatinib: 32.8%, TBP: 10.8%, P = 0.01). Lapatinib median OS was 13.0 months (95% CI: 9.5-16.5) vs. 31.0 for TBP (95% CI: 20.6-41.4), P<0.001. On multivariate analysis, longer OS was preserved for TBP, after controlling for differences in age, adjuvant trastuzumab, duration of first-line trastuzumab therapy, brain metastases, visceral metastases and hormonal treatment [Hazard Ratio (HR) = 0.63, 95% CI: 0.40-0.99, P = 0.045]. CONCLUSION: In this comparative cohort study, OS of HER2-positive MBC patients treated with TBP was significantly longer than with lapatinib. These results might be especially relevant in settings where ado trastuzumab-emtansine (TDM-1), the current preferred agent in this setting, is not available yet for patients. PMID- 26375591 TI - Evidence that the Malaria Parasite Plasmodium falciparum Putative Rhoptry Protein 2 Localizes to the Golgi Apparatus throughout the Erythrocytic Cycle. AB - Invasion of a red blood cell by Plasmodium falciparum merozoites is an essential step in the malaria lifecycle. Several of the proteins involved in this process are stored in the apical complex of the merozoite, a structure containing secretory organelles that are released at specific times during invasion. The molecular players involved in erythrocyte invasion thus represent potential key targets for both therapeutic and vaccine-based strategies to block parasite development. In our quest to identify and characterize new effectors of invasion, we investigated the P. falciparum homologue of a P. berghei protein putatively localized to the rhoptries, the Putative rhoptry protein 2 (PbPRP2). We show that in P. falciparum, the protein colocalizes extensively with the Golgi apparatus across the asexual erythrocytic cycle. Furthermore, imaging of merozoites caught at different times during invasion show that PfPRP2 is not secreted during the process instead staying associated with the Golgi apparatus. Our evidence therefore suggests that PfPRP2 is a Golgi protein and that it is likely not a direct effector in the process of merozoite invasion. PMID- 26375592 TI - Toward hypoxia-selective rhenium and technetium tricarbonyl complexes. AB - With the aim of preparing hypoxia-selective imaging and therapeutic agents, technetium(I) and rhenium(I) tricarbonyl complexes with pyridylhydrazone, dipyridylamine, and pyridylaminocarboxylate ligands containing nitrobenzyl or nitroimidazole functional groups have been prepared. The rhenium tricarbonyl complexes were synthesized with short reaction times using microwave irradiation. Rhenium tricarbonyl complexes with deprotonated p-nitrophenyl pyridylhydrazone ligands are luminescent, and this has been used to track their uptake in HeLa cells using confocal fluorescent microscopy. Selected rhenium tricarbonyl complexes displayed higher uptake in hypoxic cells when compared to normoxic cells. A (99m)Tc tricarbonyl complex with a dipyridylamine ligand bearing a nitroimidazole functional group is stable in human serum and was shown to localize in a human renal cell carcinoma (RCC; SK-RC-52) tumor in a mouse. PMID- 26375593 TI - Correction: New fluorinated fructose analogs as selective probes of the hexose transporter protein GLUT5. AB - Correction for 'New fluorinated fructose analogs as selective probes of the hexose transporter protein GLUT5' by Olivier-Mohamad Soueidan, et al., Org. Biomol. Chem., 2015, 13, 6511-6521. PMID- 26375594 TI - Antigen-Specific Mammary Inflammation Depends on the Production of IL-17A and IFN gamma by Bovine CD4+ T Lymphocytes. AB - Intramammary infusion of the antigen used to sensitize cows by the systemic route induces a local inflammation associated with neutrophil recruitment. We hypothesize that this form of delayed type hypersensitivity, which may occur naturally during infections or could be induced intentionally by vaccination, can impact the outcome of mammary gland infections. We immunized cows with ovalbumin to identify immunological correlates of antigen-specific mammary inflammation. Intraluminal injection of ovalbumin induced a mastitis characterized by a prompt tissue reaction (increase in teat wall thickness) and an intense influx of leukocytes into milk of 10 responder cows out of 14 immunized animals. The magnitude of the local inflammatory reaction, assessed through milk leukocytosis, correlated with antibody titers, skin thickness test, and production of IL-17A and IFN-gamma in a whole-blood antigen stimulation assay (WBA). The production of these two cytokines significantly correlated with the magnitude of the milk leukocytosis following the ovalbumin intramammary challenge. The IL-17A and IFN gamma production in the WBA was dependent on the presence of CD4+ cells in blood samples. In vitro stimulation of peripheral blood lymphocytes with ovalbumin followed by stimulation with PMA/ionomycin allowed the identification by flow cytometry of CD4+ T cells producing either IL-17A, IFN-gamma, or both cytokines. The results indicate that the antigen-specific WBA, and specifically IL-17A and IFN-gamma production by circulating CD4+ cells, can be used as a predictor of mammary hypersensitivity to protein antigens. This prompts further studies aiming at determining how Th17 and/or Th1 lymphocytes modulate the immune response of the mammary gland to infection. PMID- 26375595 TI - Preparation of stimuli-responsive functionalized latex nanoparticles: the effect of spiropyran concentration on size and photochromic properties. AB - Incorporation of photochromic compounds to polymer matrix through chemical bonding results in an enhancement of photoactivity and stabilization of optical properties. Here, spiropyran ethyl acrylate monomer (SPEA) was synthesized, and then photochromic particles bearing epoxy functional groups were prepared through semicontinuous emulsion copolymerization. Dynamic light scattering (DLS) and scanning electron microscopy (SEM) results depicted an increase in particle size and particle size distribution with the increase in SPEA monomer-surfactants ratio. Studies on photochromic properties by UV-vis analysis demonstrated a decrease in the absorption intensity despite the increase in SPEA content due to the enhancement in particle size. The prepared acrylic copolymer particles showed reasonable photostability, photoreversibility, and fast photoresponsivness according to the convenient test methods under UV/vis irradiation. DSC and DMTA analyses indicate an increase in Tg of the obtained copolymers with the increase in SPEA content. Finally, stimuli-responsive cellulosic papers were prepared by impregnation, and their photochromic behavior was investigated in dry and wet forms in various media under UV radiation. Morphology studies, due to stabilization of the photochromic copolymer on cellulose fibers, were conducted by SEM micrographs and showed good adhesion and compatibility between the two phases. PMID- 26375596 TI - Near-peer driven dissection selective: A primer to the medical school anatomy course. AB - In the anatomy laboratory, skill remains a critical component to unlocking the true value of learning from cadaveric dissection. However, there is little if any room for provision of instruction in proper dissection technique. We describe how near-peer instructors designed a supplemental learning activity to enhance the dissection experience for first-year medical students. This study aimed to evaluate the efficacy of this curriculum in improving participants' understanding of dissection technique and its impact on perceived challenges associated with the anatomy course. Curriculum was designed under faculty guidance and included didactic sessions, low-fidelity models, dissection, student presentations, and clinical correlations. Participants' (n = 13) knowledge of basic dissection techniques and concepts were assessed before the selective, and both participants' and nonparticipants' (n = 39) knowledge was assessed at the end of week one and week seven of the anatomy course. Scores were compared using repeated measures ANOVA followed by post hoc t-tests. Thirteen deidentified reflective essays were reviewed by four independent reviewers for themes that aligned with learning objectives. Participants in the selective course scored higher on assessment of dissection techniques and concepts one week after the selective compared to both nonparticipants and their own baseline scores before the selective. Analysis of student reflections resulted in four themes: confidence with dissection skill, sharing resources and transfer of knowledge, learning environment, and psychological impact of perceived challenges of the anatomy course. Near-peer driven supplemental exercises are effective in facilitating dissection skills. This dissection primer increases student confidence and alleviates apprehension associated with anatomy courses. PMID- 26375598 TI - Factors influencing reproduction in captive-bred cynomolgus monkeys (Macaca fascicularis) from Mauritius. AB - The cynomolgus monkey is widely used in reproductive research. However, the effects on their reproductive parameters of infant and maternal factors such as birth order, sex of infants, twin births, maternal age and lactation status have not been fully examined. The aim of this retrospective study was to determine how such infant and maternal factors impact on infant birth weight, birth viability, neonatal loss and retained placenta in cynomolgus monkeys. The study was based on birth data from a cohort of 789 females over an eight-year period. Consistent with reports made in other macaque species, female offspring had lower birth weight compared with males. Birth weights of firstborn infants were lower compared with birth weights of higher birth order infants. Results from the logistic regression analysis showed that the risk of non-viable births was increased by advancing maternal age and retained placenta. As in other non-human primates, maternal age had predictive value for non-viable births in cynomolgus monkeys. The risk of neonatal loss decreased with advancing maternal age but was not affected by birth order. Firstborn offspring did not have an increased risk for neonatal loss, possibly from the practice of retaining mothers in their natal groups, which improved maternal skills in primiparous females. However, infant low birth weight and non-lactating females increased the risk of neonatal loss, and the delivery of low birth weight infants was associated with retained placenta. The results from this study can be useful for scientists conducting reproductive studies and for colony managers in maximizing fertility and infant survival of cynomolgus monkeys. PMID- 26375597 TI - Extremely High Mutation Rate of HIV-1 In Vivo. AB - Rates of spontaneous mutation critically determine the genetic diversity and evolution of RNA viruses. Although these rates have been characterized in vitro and in cell culture models, they have seldom been determined in vivo for human viruses. Here, we use the intrapatient frequency of premature stop codons to quantify the HIV-1 genome-wide rate of spontaneous mutation in DNA sequences from peripheral blood mononuclear cells. This reveals an extremely high mutation rate of (4.1 +/- 1.7) * 10-3 per base per cell, the highest reported for any biological entity. Sequencing of plasma-derived sequences yielded a mutation frequency 44 times lower, indicating that a large fraction of viral genomes are lethally mutated and fail to reach plasma. We show that the HIV-1 reverse transcriptase contributes only 2% of mutations, whereas 98% result from editing by host cytidine deaminases of the A3 family. Hypermutated viral sequences are less abundant in patients showing rapid disease progression compared to normal progressors, highlighting the antiviral role of A3 proteins. However, the amount of A3-mediated editing varies broadly, and we find that low-edited sequences are more abundant among rapid progressors, suggesting that suboptimal A3 activity might enhance HIV-1 genetic diversity and pathogenesis. PMID- 26375599 TI - Methylene Blue-Mediated Photodynamic Inactivation Followed by Low-Laser Therapy versus Miconazole Gel in the Treatment of Denture Stomatitis. AB - PURPOSE: Photodynamic therapy (PDT) appears to be an effective method for the in vitro and in vivo inactivation of Candida spp., but no clinical trials in this context have yet been conducted. The aim of this study was to compare the effect of oral miconazole gel to PDT combined with low-power laser (LPL) therapy in the treatment of denture stomatitis. MATERIALS AND METHODS: Forty participants with clinical and microbiological diagnoses of type II denture stomatitis were randomly allocated to two treatment groups (PDT and miconazole gel), each with 20 individuals. The PDT group was submitted to one session of methylene blue mediated PDT plus two sessions of low-laser therapy twice a week for 15 days. The miconazole group was submitted to the drug four times a day for 15 days. RESULTS: Forty percent of the patients achieved clinical and microbiological resolution of denture stomatitis after methylene blue-mediated photodynamic inactivation followed by low-laser therapy. The cure rate associated with miconazole was 80% (p < 0.05). Fifteen days after the end of treatment, the recurrence rate was 25% in patients treated with PDT combined with LPL therapy and 12.5% in patients treated with miconazole. CONCLUSION: Miconazole gel provides better results than a protocol combining methylene blue-mediated PDT and LPL therapy in the treatment of type II denture stomatitis. PMID- 26375602 TI - Error in Author Name. PMID- 26375603 TI - Total Syntheses of Aporphine Alkaloids via Benzyne Chemistry: An Approach to the Formation of Aporphine Cores. AB - Total syntheses of lysicamine, (+/-)-nuciferine, (+/-)-nornuciferine, (+/-) zanthoxyphylline iodide, (+/-)-O-methylisothebaine, and (+/-) trimethoxynoraporphine were accomplished by an approach that involves the formation of aporphine cores through reactions between an isoquinoline derivative and silylaryl triflates promoted by CsF. Unprecedented formations of aporphine cores proceeded in good yields presumably through [4 + 2] cycloaddition reactions followed by hydrogen migrations. PMID- 26375604 TI - Effect of Common Excipients on the Oral Drug Absorption of Biopharmaceutics Classification System Class 3 Drugs Cimetidine and Acyclovir. AB - The objective was to assess the impact of larger than conventional amounts of 14 commonly used excipients on Biopharmaceutics Classification System (BCS) class 3 drug absorption in humans. Cimetidine and acyclovir were used as model class 3 drugs across three separate four-way crossover bioequivalence (BE) studies (n = 24 each) in healthy human volunteers, denoted as study 1A, 1B, and 2. In study 1A and 1B, three capsule formulations of each drug were manufactured, collectively involving 14 common excipients. Capsule formulations that incorporated hydroxypropyl methylcellulose (HPMC) or magnesium stearate exhibited lower absorption. The cimetidine commercial solution contained sorbitol and also resulted in lower absorption. Hence, in study 2, two capsule formulations with lower amounts of HPMC and magnesium stearate, the sorbitol-containing commercial solution, and a sorbitol-free solution were assessed for BE. Overall, 12 common excipients were found in large amounts to not impact BCS class 3 drug absorption in humans, such that these excipients need not be qualitatively the same nor quantitatively very similar to reference, but rather simply be not more than the quantities studied here. Meanwhile, for each HPMC and microcrystalline cellulose, BCS class 3 biowaivers require these two excipients to be qualitatively the same and quantitatively very similar to the reference. PMID- 26375605 TI - Sperm competition and the evolution of precopulatory weapons: Increasing male density promotes sperm competition and reduces selection on arm strength in a chorusing frog. AB - Sperm competition theory assumes a trade-off between precopulatory traits that increase mating success and postcopulatory traits that increase fertilization success. Predictions for how sperm competition might affect male expenditure on these traits depend on the number of competing males, the advantage gained from expenditure on weapons, and the level of sperm competition. However, empirical tests of sperm competition theory rarely examine precopulatory male expenditure. We investigated how variation in male density affects precopulatory sexual selection on male weaponry and the level of sperm competition in the chorusing frog Crinia georgiana, where males use their arms as weapons in male-male combat. We measured body size and arm girth of 439 males, and recorded their mating success in the field. We found density-dependent selection acting on arm girth. Arm girth was positively associated with mating success, but only at low population densities. Increased male density was associated with higher risk and intensity of sperm competition arising from multimale amplexus, and a reversal in the direction of selection on arm girth. Opposing patterns of pre- and postcopulatory selection may account for the negative covariation between arm girth and testes across populations of this species. PMID- 26375606 TI - RESOLFT Nanoscopy of Fixed Cells Using a Z-Domain Based Fusion Protein for Labelling. AB - RESOLFT super-resolution microscopy allows subdiffraction resolution imaging of living cells using low intensities of light. It relies on the light-driven switching of reversible switchable fluorescent proteins (RSFPs). So far, RESOLFT imaging was restricted to living cells, because chemical fixation typically affects the switching characteristics of RSFPs. In this study we created a fusion construct (FLASR) consisting of the RSFP rsEGFP2 and the divalent form of the antibody binding Z domain from protein A. FLASR can be used analogous to secondary antibodies in conventional immunochemistry, facilitating simple and robust sample preparation. We demonstrate RESOLFT super-resolution microscopy on chemically fixed mammalian cells. The approach may be extended to other super resolution approaches requiring fluorescent proteins in an aqueous environment. PMID- 26375607 TI - Label-free and non-invasive discrimination of HaCaT and melanoma cells in a co culture model by hyperspectral confocal reflectance microscopy. AB - A novel hyperspectral confocal microscopy method to separate different cell populations in a co-culture model is presented here. The described methodological and instrumental approach allows discrimination of different cell types using a non-invasive, label free method with good accuracy with a single cell resolution. In particular, melanoma cells are discriminated from HaCaT cells by hyperspectral confocal imaging, principal component analysis and optical frequencies signing, as confirmed by fluorescence labelling cross check. The identification seems to be quite robust to be insensitive to the cellular shape within the studied samples, enabling to separate cells according to their cytotype down to a single cell sensitivity. Set of hyperspectral images of melanoma-keratinocytes co culture model (left), score plot of principal component analysis and spectral analysis of principal components coefficients (center), label-free spectral identification of cell populations (right). PMID- 26375608 TI - Biological reaction to polyethylene particles in a murine calvarial model is highly influenced by age. AB - Particle-induced osteolysis is driven by multiple factors including bone metabolism, inflammation, and age. The objective of this study was to determine the influence of age on polyethylene (PE) particle-induced osteolysis in a murine calvarial model comparing 2-month-old (young) versus 24-month-old (old) mice. After PE particle implantation, calvaria were assessed at days (D) 3, D7, D14, and D21 via chemoluminescent imaging for inflammation (L-012 probe). In addition micro-computed tomography (micro-CT) and histomorphometry end points addressed the bone reaction. Inflammation peaked at D7 in young mice and D14 in old mice. Using micro-CT, a nadir of mature bone was recorded at D7 for young mice, versus D21 for old mice. Besides, regenerating bone peaked at distinct timepoints: D7 for young mice versus D21 for old mice. In the young mice group, the histomorphometric findings correlated with micro-CT regenerating bone findings at D7, associated with ample osteoid deposition. No osteoid could be histologically quantified in the old mice group at D7. This study demonstrated that the biological reaction to polyethylene particles is highly influenced by age. PMID- 26375609 TI - Serum Calcification Propensity Is a Strong and Independent Determinant of Cardiac and All-Cause Mortality in Kidney Transplant Recipients. AB - Calcification of the vasculature is associated with cardiovascular disease and death in kidney transplant recipients. A novel functional blood test measures calcification propensity by quantifying the transformation time (T50 ) from primary to secondary calciprotein particles. Accelerated T50 indicates a diminished ability of serum to resist calcification. We measured T50 in 1435 patients 10 weeks after kidney transplantation during 2000-2003 (first era) and 2009-2012 (second era). Aortic pulse wave velocity (APWV) was measured at week 10 and after 1 year in 589 patients from the second era. Accelerated T50 was associated with diabetes, deceased donor, first transplant, rejection, stronger immunosuppression, first era, higher serum phosphate and lower albumin. T50 was not associated with progression of APWV. During a median follow-up of 5.1 years, 283 patients died, 70 from myocardial infarction, cardiac failure or sudden death. In Cox regression models, accelerated T50 was strongly and independently associated with both all-cause and cardiac mortality, low versus high T50 quartile: hazard ratio 1.60 (95% confidence interval [CI] 1.00-2.57), ptrend = 0.03, and 3.60 (95% CI 1.10-11.83), ptrend = 0.02, respectively. In conclusion, calcification propensity (T50 ) was strongly associated with all-cause and cardiac mortality of kidney transplant recipients, potentially via a cardiac nonAPWV-related pathway. Whether therapeutic improvement of T50 improves outcome awaits clarification in a randomized trial. PMID- 26375610 TI - Effectiveness of Coupled Application of AmpFlSTR Yfiler Kit and Reduced Size Y chromosomal Short Tandem Repeat Analysis for Archeological Human Bones. AB - The AmpFlSTR Yfiler PCR Amplification (Yfiler) kit continues to be improved for a better analytical efficiency in cases of highly degraded DNA. The authors endeavored to determine whether coupling of the Yfiler kit with supplemental multiplex amplification of some Y-STR loci is a more efficient analytical mode for poorly preserved human femurs (n = 15) discovered at Korean archeological sites. To reveal locus profiles not easily obtained by Yfiler analysis, custom designed primers were adopted for the DYS390, DYS391, DYS392, DYS438, DYS439, and DYS635 loci. The success rate for 16 Y-STR locus profiles obtained from the 15 femurs was improved from 18.33% (in the use of Yfiler kit only) to 49.17% (the coupled use of Yfiler and custom-designed primers). In this study, the authors established that the custom-designed primers offer a markedly improved success rate for obtainment of Y-STR profiles from degraded aDNA not easily identified by sole use of the Yfiler assay. PMID- 26375611 TI - Some Clarifications About Water-Aided Colonoscopy. PMID- 26375612 TI - What Role Do Immunomodulators Have in Assessing Response to Curcumin as an Add-on Therapy for Patients With Ulcerative Colitis? PMID- 26375613 TI - Low Risk of Birth Defects for Infants Whose Mothers Are Treated With Anti-Tumor Necrosis Factor Agents During Pregnancy. AB - BACKGROUND & AIMS: Safety data on anti-tumor necrosis factor (anti-TNF) treatment during pregnancy are limited. We studied the risk of birth defects after anti-TNF treatment in early pregnancy. METHODS: We collected data on 1,272,424 live-born infants identified from the Danish (2004-2012) and Swedish (2006-2012) population based health registers. We determined the prevalence of birth defects among infants born to women with chronic inflammatory disease (inflammatory bowel disease, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, or psoriasis), with (n = 683) and without (n = 21,549) anti-TNF treatment during early pregnancy, and in the general population. We compared the risk of any major birth defect and birth defect by organ system for infants born to women with chronic inflammatory disease, with and without anti-TNF treatment. Risks were presented as odds ratios (ORs) with 95% confidence intervals (CIs). We adjusted for maternal age, parity, smoking, body mass index, multiple gestation, country, and chronic inflammatory diagnosis. RESULTS: Birth defects were more prevalent among infants born to women with chronic inflammatory disease, regardless of anti TNF treatment status, than in the general population (4.8% vs 4.2%). Birth defects occurred in 43 of the infants born to the 683 women who received anti-TNF treatment (6.3%), and 1019 of the infants born to women with chronic inflammatory disease (4.7%). The OR for any defect in women receiving anti-TNF therapy was 1.32 (95% CI, 0.93-1.82); the OR for a cardiovascular defect was 1.60 (95% CI, 0.93-2.58), and the OR for a urinary defect was 2.22 (95% CI, 0.86-4.71). CONCLUSIONS: Based on an analysis of data from the health registries in Denmark and Sweden, women who received anti-TNF agents during pregnancy had a slightly (but not significantly) higher risk of having children with birth defects. Although larger studies are needed, the heterogeneity of the observed birth defects did not indicate a common etiology. PMID- 26375614 TI - Replacement of filters for respirable quartz measurement in coal mine dust by infrared spectroscopy. AB - The objective of this article is to compare and characterize nylon, polypropylene (PP), and polyvinyl chloride (PVC) membrane filters that might be used to replace the vinyl/acrylic co-polymer (DM-450) filter currently used in the Mine Safety and Health Administration (MSHA) P-7 method (Quartz Analytical Method) and the National Institute for Occupational Safety and Health (NIOSH) Manual of Analytical Methods 7603 method (QUARTZ in coal mine dust, by IR re-deposition). This effort is necessary because the DM-450 filters are no longer commercially available. There is an impending shortage of DM-450 filters. For example, the MSHA Pittsburgh laboratory alone analyzes annually approximately 15,000 samples according to the MSHA P-7 method that requires DM-450 filters. Membrane filters suitable for on-filter analysis should have high infrared (IR) transmittance in the spectral region 600-1000 cm(-1). Nylon (47 mm, 0.45 um pore size), PP (47 mm, 0.45 um pore size), and PVC (47 mm, 5 um pore size) filters meet this specification. Limits of detection and limits of quantification were determined from Fourier transform infrared spectroscopy (FTIR) measurements of blank filters. The average measured quartz mass and coefficient of variation were determined from test filters spiked with respirable alpha-quartz following MSHA P 7 and NIOSH 7603 methods. Quartz was also quantified in samples of respirable coal dust on each test filter type using the MSHA and NIOSH analysis methods. The results indicate that PP and PVC filters may replace the DM-450 filters for quartz measurement in coal dust by FTIR. PVC filters of 5 um pore size seemed to be suitable replacement although their ability to retain small particulates should be checked by further experiment. PMID- 26375615 TI - Surviving Overwhelming Challenges: Family Caregivers' Lived Experience of Caring for a Child Diagnosed with HIV and Enrolled in Antiretroviral Treatment in Ethiopia. AB - Family caregivers play a critical role in caring for children living with HIV, however, there is little knowledge about their experiences. The aim of this study was to illuminate the family caregivers' lived experiences of caring for a child when he or she has been diagnosed with HIV and enrolled to antiretroviral treatment. Qualitative interviews with 21 family caregivers of 21 children diagnosed with HIV were analyzed using an inductive design with a hermeneutic phenomenological approach. The caregivers' experience were articulated in 5 subthemes under the main theme of "Surviving overwhelming challenges": "Committed care-giving," "Breaking the family life," "Caring burdens," "Confronting conflicts," and "Living with worry." Despite the difficult situation the family caregivers experienced with extensive worry, caring burdens, and disrupted family and social networks, they were committed caregivers. They were empowered by their belief in God but also by their strong belief in the child's treatment and support from healthcare workers. The healthcare system needs to consider possible ways to support the family caregivers during child's HIV diagnosis and treatment initiation as part of a continuum of care. PMID- 26375616 TI - Clinical Research Abstracts of the British Equine Veterinary Association Congress 2015. AB - REASONS FOR PERFORMING STUDY: New therapeutic strategies to modulate immune responses in human and equine allergic airway diseases are under extensive investigation. Stimulation of Treg cells with immune modulating agents is a novel therapeutic option. OBJECTIVES: The aim of this field study was to compare the effects of a nebulised nanoparticulate CpG immunotherapy (CpG-GNP) with and without specific allergens. STUDY DESIGN: Longitudinal clinical study comparing 2 therapeutic options. METHODS: Twenty RAO-affected horses were divided into 2 treatment groups (CpG alone and CpG with allergens). Two specific allergens were selected for each horse according to anamnesis and a functional in vitro test. Treatments were given by nebulisation 7 times and the horses were examined 3 times: baseline (I), after the treatment course (II), and after 6 weeks later (III). Clinical parameters, indirect intrapleural measurement, arterial blood gas, amount of tracheal mucus and neutrophil percentage were evaluated. RESULTS: CpG alone resulted in a significant improvement in clinical parameters and a significant reduction of tracheal mucus after treatment and at 6 weeks post treatment. After CpG plus specific allergens, there was significant improvement of 70% of examined parameters. However, there were no significant differences in the results compared with CpG-GNP treatment alone. CONCLUSIONS: There were no significant differences between treatment groups. CpG-GNP immunotherapy alone produced a potent and persistent effect on allergic and inflammatory parameters and may have potential as for treatment of equine and human allergic inflammatory airway diseases. Ethical animal research: The study was approved by the regional legal agency for animal experiments of the Government of Bavaria, Germany (No. 55.2-1-54-2531-31-10). Owners gave informed consent for their horses' inclusion in the study. Sources of funding: Partly supported by the Deutsche Forschungsgemeinschaft (DFG) (Germany) (GE'2044/4-1). The AeroNeb GoTM vibrating mesh nebuliser (Aerogen, Galway, Ireland) was sponsored by Inspiration Medical (Bochum, Germany). Competing interests: None declared. PMID- 26375617 TI - Systematic review of sarcopenia in patients operated on for gastrointestinal and hepatopancreatobiliary malignancies. AB - BACKGROUND: Preoperative risk assessment in cancer surgery is of importance to improve treatment and outcome. The aim of this study was to assess the impact of CT-assessed sarcopenia on short- and long-term outcomes in patients undergoing surgical resection of gastrointestinal and hepatopancreatobiliary malignancies. METHODS: A systematic search of Embase, PubMed and Web of Science was performed to identify relevant studies published before 30 September 2014. PRISMA guidelines for systematic reviews were followed. Screening for inclusion, checking the validity of included studies and data extraction were carried out independently by two investigators. RESULTS: After screening 692 records, 13 observational studies with a total of 2884 patients were included in the analysis. There was wide variation in the reported prevalence of sarcopenia (17.0 79 per cent). Sarcopenia was independently associated with reduced overall survival in seven of ten studies, irrespective of tumour site. Hazard ratios (HRs) of up to 3.19 (hepatic cancer), 1.63 (pancreatic cancer), 1.85 (colorectal cancer) and 2.69 (colorectal liver metastases, CLM) were reported. For oesophageal cancer, the HR was 0.31 for increasing muscle mass. In patients with colorectal cancer and CLM, sarcopenia was independently associated with postoperative mortality (colorectal cancer: odds ratio (OR) 43.3), complications (colorectal cancer: OR 0.96 for increasing muscle mass; CLM: OR 2.22) and severe complications (CLM: OR 3.12). CONCLUSION: Sarcopenia identified before surgery by single-slice CT is associated with impaired overall survival in gastrointestinal and hepatopancreatobiliary malignancies, and increased postoperative morbidity in patients with colorectal cancer with or without hepatic metastases. PMID- 26375618 TI - The role of smokeless tobacco use in smoking persistence among male college students. AB - BACKGROUND: Significant changes in the tobacco industry have led to heightened concern about co-use of cigarettes and smokeless tobacco (SLT) products. OBJECTIVES: The aim of this study was to assess whether male cigarette smokers who also used SLT products, in the first semester of their first year of college, were more or less likely than male cigarette smokers who did not use SLT products to still be smoking by the first semester of their senior year. METHODS: Using a longitudinal, observational study, we followed a cohort of undergraduate students from 11 four-year universities in North Carolina and Virginia through their college career. Mixed-effects logistic regression analysis was conducted to estimate the likelihood of being a current smoker fall of senior year for male students who used both cigarettes and SLT at baseline, compared to those who only smoked cigarettes, after adjustment for potential confounders (n = 274). RESULTS: At baseline, 67.2% of participants were smoking cigarettes only (no SLT use) and 32.8% were dual users (cigarettes and SLT). A total of 62% were still smoking at senior year. Dual users were 30% more likely to be current smokers senior year compared to cigarette only users, although this difference was not statistically significant. Having at least one friend who smoked cigarettes and heavier cigarette smoking at baseline were significantly related to senior year smoking. CONCLUSIONS: Our findings do not support the argument that SLT use may help male college smokers discontinue their smoking habit. In fact, it may contribute to smoking persistence. PMID- 26375619 TI - Helicobacter pylori neutrophil-activating protein induces release of histamine and interleukin-6 through G protein-mediated MAPKs and PI3K/Akt pathways in HMC-1 cells. AB - Helicobacter pylori neutrophil-activating protein (HP-NAP) activates several innate leukocytes including neutrophils, monocytes, and mast cells. It has been reported that HP-NAP induces degranulation and interleukin-6 (IL-6) secretion of rat peritoneal mast cells. However, the molecular mechanism is not very clear. Here, we show that HP-NAP activates human mast cell line-1 (HMC-1) cells to secrete histamine and IL-6. The secretion depends on pertussis toxin (PTX) sensitive heterotrimeric G proteins but not on Toll-like receptor 2. Moreover, HP NAP induces PTX-sensitive G protein-mediated activation of extracellular signal regulated kinase 1/2 (ERK1/2), p38-mitogen-activated protein kinase (p38 MAPK), and Akt in HMC-1 cells. Inhibition of ERK1/2, p38 MAPK, or phosphatidylinositol 3 kinase (PI3K) suppresses HP-NAP-induced release of histamine and IL-6 from HMC-1 cells. Thus, the activation of HMC-1 cells by HP-NAP is through Gi-linked G protein-coupled receptor-mediated MAPKs and PI3K/Akt pathways. PMID- 26375621 TI - Bearing Surfaces in Total Knee Replacement. PMID- 26375620 TI - Chronic estrogen exposure affects gene expression in the rostral ventrolateral medulla of young and aging rats: Possible role in hypertension. AB - BACKGROUND: Chronic exposure to estradiol-17beta (E2) in adult female rats increases mean arterial pressure by stimulating superoxide production in the rostral ventrolateral medulla (RVLM). However the mechanisms behind this phenomenon are unknown. We hypothesized that E2 exposure induces the gene expression of cytokines, chemokines and NADPH oxidase (Nox) in the RVLM that promotes superoxide production and aging would exacerbate this effect. METHODS: Young adult (3-4 month old) and middle-aged (6-8 month old) female Sprague Dawley rats were sham-implanted (YS and MS respectively) or implanted s.c. with slow release E2 pellets (20 ng of E2/day for 90 days; YE and ME respectively). Blood pressure (BP) was measured during the last 3 weeks of exposure in a separate set of rats. At the end of treatment, the animals were sacrificed and RVLM was isolated from the brainstem. PCR array and Quantitative RT-PCR were performed with the tissue to quantify genes associated with hypertension and superoxide production. Superoxide dismutase (SOD) activity was also measured in the RVLM from a different set of animals. RESULTS: E2 exposure increased mean arterial pressure in both YE and ME animals. Inflammatory genes such as interleukin-1beta, interleukin-6 and monocyte chemoattractant protein-1 were significantly up regulated in the RVLM of ME treated female rats compared to YS rats, but not in YE rats. Endothelin-1 (ET-1) gene was up-regulated in the RVLM of both YE and ME rats that were exposed to E2. Furthermore, chronic E2 treatment increased the mRNA levels of Nox1 and Nox2 genes in the RVLM of YE but not ME animals. SOD activity was reduced in MA animals, compared to young animals. E2 treatment had no significant effect on SOD activity. CONCLUSION: Chronic E2 exposure stimulates the expression of inflammatory genes in older animals and increases the expression of Nox subunits in the RVLM of younger animals. SOD activity was reduced in older animals. This suggests increased superoxide production in younger animals, but reduced superoxide elimination in older animals. On the other hand, E2 exposure stimulates ET-1 expression in both young and aging animals. These findings suggest that hypertension caused by chronic E2 exposure may involve different molecular mediators in young and aging animals, however ET 1 and superoxide could be common mediators for both age groups. PMID- 26375622 TI - A review of ethylphenidate in deaths in east and west Scotland. AB - Ethylphenidate is a psychostimulant and analogue of methylphenidate. Interestingly it is also produced as a metabolite from the co-ingestion of methylphenidate and alcohol (ethanol). In the UK, between April and June 2015, ethylphenidate and 6 other methylphenidate based novel psychoactive substances (NPS) were subjected to a temporary class drug order under the Misuse of Drugs Act 1971. Ethylphenidate is being abused by both novel and habitual drug users, more prominently in the East of Scotland. What is unknown in the literature is the contribution of ethylphenidate in deaths. A search was conducted for an 18 month period (July 2013 to December 2014) to identify cases where ethylphenidate was detected during post-mortem toxicological analysis. Nineteen cases were identified and these cases were examined with regards to case circumstances, pathology findings, toxicology results and adverse effects. The individuals ranged in age from 20 to 54 (median 37) and the majority were male (n=14) and from the East of Scotland (n=16), more specifically Edinburgh and surrounding area. Current or previous heroin abuse was a common theme in these cases (n=16) and injection was a common route of administration of "legal highs" or "burst". The concentration of ethylphenidate in the cases ranged from 0.008 mg/L to over 2 mg/L in post-mortem femoral blood (median 0.25 mg/L, average 0.39 mg/L). Other drugs commonly detected were benzodiazepines (n=15), followed by opiates (n=11, 4 of which were positive for 6-monoacetylmorphine) and then methadone (n=8). All 19 cases received a full post-mortem examination and there were 10 cases where drug toxicity was the sole or potentially contributory factor to the cause of death. Ethylphenidate was specifically mentioned in the cause of death for 5 cases, chronic intravenous (IV) drug use was named as part of the cause of death for 2 cases and in 6 cases there was evidence of complications and infections through IV drug use. As far as it is known to the authors, this is the first review of post-mortem cases involving the use of ethylphenidate in East and West Scotland. This study can be used as a guide for toxicologists and pathologists when interpreting cases which are positive for ethylphenidate. PMID- 26375625 TI - Recurrent ischemic stroke can happen in stroke patients very early after intravenous thrombolysis. PMID- 26375624 TI - Identification of a new target muscle for treatment in patients with Parkinson's disease who have lateral trunk flexion? AB - Parkinson's disease (PD) can present with lateral trunk flexion (LTF). Abnormal posture associated with PD has been treated, but the effectiveness of these treatments is limited, resulting in unsatisfactory outcomes. Unilateral hypertrophy and unilateral hyperactivity may be useful for deciding targets for injection of botulinum toxin or physical rehabilitation. However, such findings may be limited such as the obliquus abdominis muscle or thoracic paraspinal muscles, and several other muscles may have a causative role in LTF. We investigated 8 patients whether other muscles show unilateral hypertrophy by analyzing computed tomographic scans. Cobb's angle was 11 degrees to 34 degrees . The area of the paravertebral muscles was large contralateral to the bending side and this trend intensified from L4 to Th10. The lumbar quadrate muscle and psoas major muscle showed unilateral enlargement. These larger muscles were prominent contralateral to the bending side in five patients and ipsilateral to the bending side in two patients. This unilateral muscle change was mildly seen in the internal and external abdominal oblique muscles. The lumbar quadrate muscle or psoas major muscle showed two hypertrophic patterns, and these muscles might be new therapeutic targets for treatments such as botulinum toxin. PMID- 26375623 TI - Itemized NIHSS subsets predict positive MRI strokes in patients with mild deficits. AB - BACKGROUND: While imaging is useful in confirming the diagnosis of ischemic stroke, negative diffusion weighted imaging (DWI) is reported in up to 25% of patients. Our aim was to identify predictors of MRI-positive stroke from the itemized NIHSS. METHODS: Data were derived from the Stroke Warning Information and Faster Treatment study from February 2006 to February 2010 among patients with mild deficits (NIHSS 0-5) and a final diagnosis of stroke by a vascular neurologist. All MRI sequences were reviewed for the presence or absence of an acute infarct on DWI. Multivariate logistic regression assessed factors predicting DWI-positive strokes; p<0.05 was considered significant. RESULTS: 894 patients had a discharge diagnosis of stroke; 709 underwent MRI and 28.0% were DWI negative. All patients with visual field deficits or neglect were DWI positive. On multivariate analysis including total NIHSS (0-2 vs. 3-5) and itemized NIHSS score subsets, predictors of a positive DWI were NIHSS score of 3 5 (OR=3.3, 95% CI: 1.8-6.1), motor deficits (OR=1.7, 95% CI: 1.1-2.8), ataxia (OR=1.9, 95% CI: 1.0-3.5), and absence of sensory deficits (OR=1.7, 95% CI: 1.0 2.7). We developed the NIHSS-m score that predicts DWI positivity in patients with mild deficits in the absence of neglect or visual field deficits. CONCLUSION: NIHSS score subsets predict DWI positivity in mild strokes. The presence of neglect or visual field deficits on the NIHSS subsets is most likely to have an MRI correlate even in patients with low NIHSS. PMID- 26375626 TI - Access to Cytotoxic Medicines by Children With Cancer: A Focus on Low and Middle Income Countries. AB - BACKGROUND: The Essential Medicines Working Group of the International Society of Pediatric Oncology (SIOP) has proposed a list of antineoplastic drugs that should be available in low and middle income countries. PROCEDURE: Data were extracted on the listing of 18 essential and 8 ancillary antineoplastic medicines in the national essential medicines lists (NEMLs) or national reimbursable medicines lists (NRMLs) of 135 countries with gross national income (GNI) per capita of less than US $25,000. Correlations between numbers of medicines listed and GNI per capita, annual government health expenditure (AGHE) per capita, and the number of physicians per million people were examined. RESULTS: Listing of the 18 essential antineoplastic drugs ranged from 27% (thioguanine) to 95% (methotrexate). The median number of medicines listed was 7 (0-18) in low income countries (n = 26) and 14 in lower-middle (n = 42), upper-middle (n = 44), and high income countries (n = 20). For the ancillary eight medicines, the median was one (0-8) across the 135 countries. Correlations with GNI per capita (r = 0.17, P = 0.0266) and physician density (r = 0.25, P = 0.0017) were statistically significant; not so for AGHE per capita (r = 0.00, P = 0.5000). CONCLUSIONS: There was large variability within income groups in numbers of antineoplastic agents identified as essential in NEMLs and NRMLs. While not a direct measure of availability, listing is an important step, guiding procurement for the public sector. These results focus attention on deficits in NEMLs and NMRLs as a step to improving access to effective antineoplastic medicines for cancers in children in low and middle income countries. PMID- 26375627 TI - Structural and energetic requirements for a second binding site at the dimeric beta-lactoglobulin interface. AB - Through experimental and theoretical approaches, it has been shown that bovine beta-lactoglobulin (betalg) uses its hydrophobic cavity or calyx as the primary binding site for hydrophobic molecules, whereas the existence of a second ligand binding site at the dimeric interface has only been structurally identified for vitamin D3 (VD3). This binding exists even in the thermally denatured state, suggesting the prevalence of this secondary site. Although crystallographic experiments have suggested that VD3 can bind to both monomeric and dimeric states without significant structural differences, theoretical and experimental reports have proposed some structural requirements. Thus, in this study, based on known experimental data, the dynamic interaction of VD3 with the monomeric or dimeric forms of betalg was investigated through a protocol combining blind docking and 2 microsecond molecular dynamics simulations coupled with binding free energy and per-residue binding free energy decomposition analyses using the Molecular Mechanics Generalized Born Surface Area approach. Binding free energy calculations allowed us to estimate the energetic differences of coupling VD3 at the calyx and the dimeric interface for the monomeric or dimeric state, revealing that the dimeric structure is required to form a stable complex with VD3 at the dimeric interface. This also has an important impact on the dimerization process, whereas although the monomeric state also forms a stable complex with VD3 at the dimeric interface, the incorporation of the entropy component contributed to producing a marginally favorable binding free energy. Finally, the per-residue decomposition analysis provided energetic information about the most relevant residues in stabilizing the different systems. PMID- 26375628 TI - Otoacoustic emissions in young adults: Effects of blood group. AB - Previous research findings have suggested that individuals with different blood groups demonstrate varied haematological risk factors for a wide range of disorders, including noise-induced hearing loss. The present study investigated the effects of blood group on several features of otoacoustic emissions (OAEs) including magnitude, as OAE status is indicative of cochlear function. A total of 60 normal hearing females aged between 18 and 26 years were included in the study. Measurements of spontaneous otoacoustic emissions (SOAEs), transient evoked emissions (TEOAEs) and distortion-product otoacoustic emissions (DPOAEs) were obtained from both ears for all participants, who included equal numbers of A, B, O and AB positive blood groups. Participants with blood group O had significantly fewer occurrences of SOAEs and lower DPOAE amplitudes at some frequencies compared to participants with blood group B. There was a general trend for blood group O individuals to show reduced OAE amplitudes compared to participants from A, B, and AB groups. These findings are consistent with the hypothesis that individuals with different blood groups may have different OAE amplitude values. The results support the need for further investigation on the effects of blood group on OAE status. PMID- 26375629 TI - Simulator study of young driver's instinctive response of lower extremity to a collision. AB - OBJECTIVE: A driver's instinctive response of the lower extremity in braking movement consists of two parts, including reaction time and braking reaction behavior. It is critical to consider these two components when conducting studies concerning driver's brake movement intention and injury analysis. The purposes of this study were to investigate the driver reaction time to an oncoming collision and muscle activation of lower extremity muscles at the collision moment. The ultimate goal is to provide data that aid in both the optimization of intervention time of an active safety system and the improvement of precise protection performance of a passive safety system. METHOD: A simulated collision scene was constructed in a driving simulator, and 40 young volunteers (20 male and 20 female) were recruited for tests. Vehicle control parameters and electromyography characteristics of eight muscles of the lower extremity were recorded. The driver reaction time was divided into pre-motor time (PMT) and muscle activation time (MAT). Muscle activation level (ACOL) at the collision moment was calculated and analysed. RESULTS: PMT was shortest for the tibialis anterior (TA) muscle (243~317 ms for male and 278~438 ms for female). Average MAT of the TA ranged from 28-55 ms. ACOL was large (5~31% for male and 5~23% for female) at 50 km/h, but small (<12%) at 100 km/h. ACOL of the gluteus maximus was smallest (<3%) in the 25 and 100 km/h tests. ACOL of RF of men was significantly smaller than that of women at different speeds. CONCLUSIONS: Ankle dorsiflexion is firstly activated at the beginning of the emergency brake motion. Males showed stronger reaction ability than females, as suggested by male's shorter PMT. The detection of driver's brake intention is upwards of 55ms sooner after introducing the electromyography. Muscle activation of the lower extremity is an important factor for 50 km/h collision injury analysis. For higher speed collisions, this might not be a major factor. The activations of certain muscles may be ignored for crash injury analysis at certain speeds, such as gluteus maximus at 25 or 100 km/h. Furthermore, the activation of certain muscles should be differentiated between males and females during injury analysis. PMID- 26375630 TI - Syndrome of rapid onset ESRD accounted for high hemodialysis catheter use- results of a 13-year Mayo Clinic incident hemodialysis study. AB - BACKGROUND: The syndrome of rapid onset end-stage renal disease (SORO-ESRD) was first described in the journal Renal Failure in 2010. This is an acute precipitate unpredictable yet irreversible ESRD following acute kidney injury (AKI), as distinct from "classic" ESRD where chronic kidney disease (CKD)-ESRD progression was linear, time-dependent, and predictable. The overall impact of SORO-ESRD on ESRD outcomes in the adult US ESRD population remains speculative and called for larger studies. METHODS: A retrospective investigation of an incident adult ESRD population, Mayo Clinic, Rochester, 2001-2013. RESULTS: One hundred and forty-nine of 1461 (10%) incident patients with ESRD had SORO-ESRD - M:F = 76:73, age 62 (19-95) years, 139 (93%) native kidneys, and 10 (7%) renal transplant recipients (RTRs). The modal age group was 71-80 years. A total of 147 (99%) SORO-ESRD patients started first hemodialysis treatment via a dialysis catheter. Kidney biopsy in 10 RTRs and 34 native kidneys revealed acute tubular necrosis (ATN) as the commonest pathology. Cardiac arrest remained the leading cause of death among SORO-ESRD patients. CONCLUSIONS: SORO-ESRD accounted for 149 (10%) of 1461 incident ESRD patients. There was no gender disparity. The older population was more susceptible. Ninety-nine percent (99%) of SORO-ESRD patients started their first hemodialysis treatment via a dialysis catheter, a major negative impact on AV fistula first programs. ATN was the leading pathologic diagnosis. We conclude that SORO-ESRD contributes significantly to incident ESRD here in the USA including renal allograft loss. Efforts to reduce AKI incidence or renoprevention demand more attention and priority. PMID- 26375631 TI - Evidence for high-level feature encoding and persistent memory during auditory stream segregation. AB - A test sequence of alternating low-frequency (A) and high-frequency (B) tones in a repeating ". . . ABAB . . ." pattern is more likely to be heard as 2 segregated streams of tones when it is preceded by an isofrequency inducer sequence whose frequency matches either the A- or B-tone frequency (e.g., ". . . BBBB . . .") of the test, a phenomenon referred to as stream biasing. Low-level processes such as stimulus-selective adaptation of frequency-tuned neurons within early auditory processing stages have been thought by some to mediate stream biasing; however, the current study tested for the involvement of higher level processes. Inducers whose frequency matched neither the A- nor B-tone frequency (e.g., ". . . CCCC . . .") sometimes facilitated stream biasing. Stream biasing was also sensitive to complex features of the inducer sequence, namely whether the rhythmic pattern of the inducer matched the rhythm of the ABAB test. Stream biasing occurred even when an 8-s silent interval separated the inducer and test sequences, a time span longer than previously recognized (Beauvois & Meddis, 1997). These results suggest the involvement of persistent activation of high-level representations that affect perception. PMID- 26375632 TI - On the costs of parallel processing in dual-task performance: The case of lexical processing in word production. AB - Previous dual-task picture-naming studies suggest that lexical processes require capacity-limited processes and prevent other tasks to be carried out in parallel. However, studies involving the processing of multiple pictures suggest that parallel lexical processing is possible. The present study investigated the specific costs that may arise when such parallel processing occurs. We used a novel dual-task paradigm by presenting 2 visual objects associated with different tasks and manipulating between-task similarity. With high similarity, a picture naming task (T1) was combined with a phoneme-decision task (T2), so that lexical processes were shared across tasks. With low similarity, picture-naming was combined with a size-decision T2 (nonshared lexical processes). In Experiment 1, we found that a manipulation of lexical processes (lexical frequency of T1 object name) showed an additive propagation with low between-task similarity and an overadditive propagation with high between-task similarity. Experiment 2 replicated this differential forward propagation of the lexical effect and showed that it disappeared with longer stimulus onset asynchronies. Moreover, both experiments showed backward crosstalk, indexed as worse T1 performance with high between-task similarity compared with low similarity. Together, these findings suggest that conditions of high between-task similarity can lead to parallel lexical processing in both tasks, which, however, does not result in benefits but rather in extra performance costs. These costs can be attributed to crosstalk based on the dual-task binding problem arising from parallel processing. Hence, the present study reveals that capacity-limited lexical processing can run in parallel across dual tasks but only at the expense of extraordinary high costs. PMID- 26375633 TI - LRRK1 regulates spindle orientation by phosphorylating CDK5RAP2. PMID- 26375634 TI - Reproductive and developmental toxicity of carbon-based nanomaterials: A literature review. AB - We summarized the findings of reproductive and developmental toxicity studies on carbon-based nanomaterials (CNMs). Placental transfer of fullerenes in rats and single-walled (SW) and multi-walled (MW) CNTs in mice was shown after intravenous injection. SWCNTs appeared to be embryolethal and teratogenic in mice when given by intravenous injection and induced death and growth retardation in chicken embryos. In mice-administered MWCNTs, fetal malformations after intravenous and intraperitoneal injections and intratracheal instillation, fetal loss after intravenous injection, behavioral changes in offspring after intraperitoneal injection, and a delay in the delivery of the first litter after intratracheal instillation were reported. Oral gavage of MWCNTs had no developmental toxicity in mice and rats. MWCNTs produced morphological defects, developmental arrest, and death in zebrafish embryos. Intratracheal instillation of carbon black (CB) induced testicular toxicity in adult mice. Maternal airway exposure to CB in gestation had testicular toxicity and altered postnatal behavior, renal development, immune and genotoxic responses, and brain morphology in mouse offspring. Nanodiamonds and graphite nanoparticles inhibited vasculogenesis and/or angiogenesis in chicken embryos. Graphene oxide (GO) induced malformations in zebrafish embryos. Intravenous injection of reduced GO during late gestation caused maternal death and abortion in mice. Oral administration of GO during lactation caused growth retardation of offspring. Overall, the available data provide initial information on the potential reproductive and developmental toxicity of CNMs. However, confirmatory studies using well-characterized CNMs, state-of-the-art study protocol and appropriate route of exposure, are required to clarify the findings and provide information suitable for risk assessment. PMID- 26375635 TI - Clinical experience of individual surgical therapy in hypertensive basal ganglia hemorrhage. AB - BACKGROUND: The aim of this article is to summarize the clinical experience stemming from the administration of different surgical therapies in hypertensive basal ganglia hemorrhage (HBGH) patients. METHODS: A series of 87 patients with HBGH who had received surgical therapy individually were enrolled in this study. The surgical therapies were stereotactic aspiration (SA), stereotactic aspiration plus fibrinolytic therapy (SA+F) and microsurgery with small bone window (MS), respectively. The outcomes of the patients were evaluated by evolution of hematoma evacuation, activities of daily living (ADL) scale, mortality and complications. RESULTS: We found that there was no significant difference in the 24-hour evacuation rate, mortality and complication rate among treated groups (P>0.05). Though patients in level III and level IV of ADL scores were significantly different among the three groups, the overall ADL scale result demonstrated a similar ADL result. CONCLUSIONS: HBGH patients should be treated with an individualized surgical approach based on their condition and on the CT morphology of the hematoma. PMID- 26375636 TI - Treatment options and neurocognitive outcome in patients with diffuse low-grade glioma. AB - In the management of patients with low-grade glioma (LGG) there still is controversy on how surgical intervention, radiotherapy, and chemotherapy contribute to an ameliorated progression-free survival, overall survival, and treatment-related neurotoxicity. With the ongoing changes in treatment options for these patients, neurocognitive functioning is an increasingly important outcome measure, because neurocognitive impairments can have a large impact on self-care, social and professional functioning, and consequently on health related quality of life. Many factors contribute to neurocognitive outcome, such as direct and indirect tumor effects, seizures, medication, and oncological treatment. Although the role of radiotherapy has been studied extensively, the adverse effects on neurocognitive function of other treatment-related factors remain elusive. This not only holds for resective surgery, where the use of intraoperative stimulation mapping has a high potential benefit concerning survival and patient functioning, but also for the use of chemotherapy that might have some interesting new applications, like the facilitation of total resection for initially primary or recurrent diffuse LGG tumors. This paper will discuss these treatment options in LGG patients and their potential effects on neurocognitive functioning. PMID- 26375637 TI - Brazilian Collective Health in Abrascao 2015: Goiania, Capital of the Cerrado. PMID- 26375638 TI - The bill submitted to the Brazilian Senate for ethical regulation of clinical research is contrary to the interests of research subjects. PMID- 26375639 TI - [The profile of patients undergoing bariatric surgery in the Brazilian Unified National Health System: a systematic review]. AB - Nearly one million Brazilians were morbidly obese in 2013. Bariatric surgery is an option for sustained weight loss, and the Brazilian Unified National Health System (SUS) had provided 50,000 such procedures as of 2014. The SUS database does not provide anthropometric and comorbidity data on these patients, so the aim of the current study was to perform a systematic review to assess the profile of SUS patients that underwent bariatric surgery from 1998 to 2014. The MEDLINE, LILACS, SciELO, and Scopus databases were searched, and the methodological quality of the included articles was assessed. Of the 1,591 identified studies, 39 were selected, 95% of which were observational. Patients had a mean age of 41.4 years and mean body mass index of 48.6kg/m2; 21% were males, 61% hypertensive, 22% diabetics, and 31% presented sleep apnea. When compared to international study samples, SUS patients showed similar a anthropometric profile and comorbidities but higher prevalence of hypertension. The studies' low methodological quality suggests caution in interpreting the results. PMID- 26375640 TI - [Factors associated with the demand for health services by Brazilian adolescents: the National School Health Survey (PeNSE), 2012]. AB - The objectives of this study were to describe the demand for health services by adolescents and to identify associated factors. The study analyzed data from the National School Health Survey 2012 and calculated prevalence rates and 95% confidence intervals (95%CI). Data analysis used age-adjusted logistic regression. Half of all students required health services and the proportion was higher in girls. Factors associated with demand for health services were white skin color, enrollment in private school, maternal schooling >= 12 years, sexual activity, injuries, toothache, attempts to maintain, lose, or gain weight, wheezing, appropriate hygiene, and parents knowing what their children did in their free time. The highest demand for health services was mainly by girls, and demand was associated with socio-demographic characteristics, symptoms, and health risk/protective behaviors. PMID- 26375641 TI - HIV-testing among female sex workers on the border between Brazil and French Guiana: the need for targeted interventions. AB - The border between Brazil and French Guiana is a place of economic, cultural, social and sexual exchange. Female sex workers represent a high risk population for HIV in this area where sexual tourism is particularly developed. HIV testing seems to be an important element in the fight against the epidemic. Indeed, early HIV testing gives access to treatments and prevention. An HIV/AIDS knowledge, attitudes, behaviors and practices survey was conducted in 2011 among sex workers along the border between Brazil and French Guiana. A total of 213 female sex workers were interviewed. One third (31.5%) of the interviewed had never tested for HIV. Factors associated with non HIV-testing were the lack of knowledge of places where to do an HIV test, to be 30 or older, feeling at risk of HIV, not evaluating one's own risk towards HIV, and living in Oiapoque. These results clearly suggest that targeted interventions are needed to encourage and assist female sex workers to get tested regularly. PMID- 26375642 TI - Advanced activities of daily living and incidence of cognitive decline in the elderly: the SABE Study. AB - The objective of this study was to evaluate the association between advanced activities of daily living (AADL) and incidence of cognitive decline. The sample consisted of non-institutionalized older adults who participated in the second (2006) and third (2010) waves of the Health, Wellbeing, and Aging (SABE) cohort study in Sao Paulo, Brazil. Cognitive decline was measured using a modified Mini Mental State Examination. Advanced activities of daily living covered 12 social, productive, physical, and leisure-time activities that involve higher cognitive functions. Other covariates included socio-demographic conditions, overall health, lifestyle, and functional disability. The association between the independent variables and incidence of cognitive decline was assessed by multiple Poisson regression. Incidence of cognitive decline was 7.9%. Mean number of AADL in 2006 was significantly higher among elders who had not developed cognitive decline. Multivariate analysis showed that the number of AADL performed was a significant inverse predictor of cognitive decline. PMID- 26375643 TI - Relationship between social capital indicators and lifestyle in Brazilian adults. AB - The present study examined the relationship between indicators of social capital and health-related behaviors. A cross-sectional study was conducted on a sample of 1,062 participants representative of the population aged 40 years or older from a city in Southern Brazil. The following indicators of social capital were examined: number of friends, number of people they could borrow money from when in need; extent of trust in community members; number of times members of the community help each other; community safety; and extent of membership in community activities. Also, an overall score of social capital including all indicators was calculated. A poor social capital was associated with insufficient leisure-time physical activity (OR = 1.70; 95%CI: 1.07-2.70), low consumption of fruits and vegetables (OR = 1.53; 95%CI: 1.05-2.24), and smoking (OR = 1.97; 95%CI: 1.21-3.21). No clear association was found between capital social and binge drinking. A score of social capital showed an inverse relationship with the number of prevalent risk behaviors (p < 0.001). These results reinforce that policies to promote health should consider social capital. PMID- 26375644 TI - [The list of drugs in the Popular Pharmacy Program and the Brazilian National Pharmaceutical Care Policy]. AB - This study aimed to analyze the list of drugs in the Popular Pharmacy Program in Brazil (PFPB) in relation to the country's pharmaceutical care policy. The list of drugs in the PFPB was compared to the Brazilian and international reference lists of essential medicines, the components of pharmaceutical care in Brazilian Unified National Health System (SUS), and drug production by the country's government pharmaceutical laboratories. The PFPB list includes 119 drugs, of which 19.3% and 47.1% were not selected on the Brazilian and international reference lists, respectively; 16.8% are not used in primary care, and 40.3% are not produced by the country's government laboratories. A revision of the PFPB list based on the essential medicines concept (World Health Organization), alignment of pharmaceutical care policies, and production by government laboratories are essential to improve quality of health care, management, training of prescribers, and information for the population. PMID- 26375645 TI - Dental caries in Uruguayan adults and elders: findings from the first Uruguayan National Oral Health Survey. AB - This study aimed to assess dental caries status and associated factors in Uruguayan adults and elders using data from the first Uruguayan National Oral Health Survey. Data were representative of the country as a whole. Socio demographic information was collected with a closed questionnaire. Dental caries was assessed by clinical examination using the DMFT index. The final sample consisted of 769 participants. Mean DMFT was 15.20 and 24.12 for the 35-44 and 65 74-year age groups, respectively. Mean number of decayed teeth was 1.70 in adults and 0.66 in elders. Multivariate analyses showed higher prevalence of dental caries associated with age 65-74 years, low socioeconomic status, use of public dental services, presence of gingivitis; for decayed teeth, age 35-44 years, low socioeconomic status, use of public dental services, infrequent tooth brushing, need for oral health care, and presence of root caries showed higher severity. Uruguayan adults and elders from disadvantaged backgrounds concentrated a heavier burden of dental caries. PMID- 26375646 TI - Breast cancer survival and health iniquities. AB - Breast cancer is the most frequent neoplasm in women, and some studies have shown social inequalities in incidence and survival, which are poorly investigated in Brazil. To assess iniquity in prognosis, a hospital-based cohort study was carried out. Follow-up was made by active search in medical records and in the Mortality Information System, phone calls, and consultation on Individual Tax Collection Record status. Survival functions were estimated by the Kaplan-Meier method, and the Cox proportional hazards model was employed for prognostic assessment. Disease-specific survival was estimated at 76.3% (95%CI: 71.9-81.0) in 5 years. Women seen at public facilities had worse prognosis (HR = 1.79; 95%CI: 1.09-2.94), which was particularly due to the disease being diagnosed at a more advanced stage. These findings point to inequalities of access to screening actions, as women of lower social conditions with later diagnostic and therefore with worse prognostic. PMID- 26375647 TI - [Obesity and overweight in adult Xukuru of Ororuba Indians, Pernambuco State, Brazil: magnitude and associated socioeconomic and demographic factors]. AB - This cross-sectional study focused on the epidemiology of overweight and obesity and the association with demographic and socioeconomic variables in a sample of 794 Xukuru of Ororuba adults 19-59 years of age, from an indigenous reserve in Pesqueira County, Pernambuco State, Brazil. Descriptive analyses and multivariate logistic regression were carried out, using cut-off points of BMI > 24.99kg/m2 for overweight and > 29.99kg/m2 for obesity. Prevalence rates of overweight and obesity were higher in women (52.2% and 21%, respectively) than in men (44.1% and 7.5%, respectively). Female sex and age (> 30 years) were associated with both outcomes in the multivariate regression. For obesity, the following variable showed statistically significant associations: socioeconomic status and the interaction between male gender and per capita income. As in other indigenous populations in Brazil, the study's findings suggest that the Xukuru are experiencing a rapid nutritional transition. PMID- 26375648 TI - [Rural workers' health in Brazil]. AB - Workers' health is a central theme in public health surveys, but the specificity of work activities should be considered. This study aimed to analyze the health of rural workers in Brazil that perform both agricultural and non-agricultural work, based on self-rated health and self-reported diseases. The Brazilian National Household Sample Survey (PNAD 2008) was used, incorporating information from the complex sampling plan. Agricultural workers 18 years or older were selected, stratified according to those with and without non-agricultural work. Logistic regression was performed for self-rated health, and odds ratios were calculated for self-reported diseases. Exclusive agricultural work decreased the odds of reporting good health and increased the odds of reporting back pain, high blood pressure, and arthritis/rheumatism. Exclusive agricultural workers reported more diseases and worse living conditions. Self-rated health was generally better in workers with non-agricultural occupations. PMID- 26375649 TI - [Proposal of an index for government measures to deal with domestic violence against children and adolescents]. AB - The article discusses the development of the Index for Dealing with Family Violence to assess municipal strategies related to this violation of children's and adolescents' rights. Development of the index involved a preliminary analysis of indicators from previous studies and a technical expert group. Four indicators were selected: the existence of a municipal plan for dealing with violence against children and adolescents; the existence of an inter-sector flow for treating and following up on children and adolescents in situations of family violence; number of guardianship councils in relation to the municipality's population; and the existence of standardized instruments in municipal school, social work, and health systems for reporting situations of violence against children and adolescents. The databank from a previous study was used in an exercise to apply the indicator in four Brazilian state capitals. The indicator can serve as a tool for monitoring and mobilizing efforts to implement measures for dealing with family violence. PMID- 26375650 TI - Spatial dynamics of AIDS incidence in the elderly in Rio de Janeiro, Brazil, 1997 2011. AB - The dynamics of the spread of the AIDS epidemic ranges according to the characteristics of each geographical region in different population groups. The aim of this study was to evaluate spatial and temporal trends of the AIDS epidemic among the elderly in the State of Rio de Janeiro, Brazil. A retrospective study using spatial analysis techniques was conducted among AIDS cases (>= 60 years) diagnosed from 1997-2011. The Poisson regression model was used to assess the relationship between year of diagnosis and incidence of AIDS, adjusted by sex. The AIDS epidemic began in the south coast of the state and gradually reached neighboring cities. The highest rates were found in regions around Rio de Janeiro and Niteroi cities. The highest smoothed rates of the period were observed in Niteroi in 2002-2006: 11.87/100,000 (men) and 8,5/100,000 (women). AIDS incidence rates among the elderly have stabilized in recent decades. To prevent HIV from spreading further among the general population, greater attention should be given to the older population. PMID- 26375651 TI - Association between age and survival in a cohort of Brazilian patients with operable breast cancer. AB - Whether age is an independent prognostic factor in breast cancer is a matter of debate. This is a retrospective cohort study of 767 breast cancer patients, stages I-III, treated at the Hospital das Clinicas, Minas Gerais Federal University, Belo Horizonte, Minas Gerais State, Brazil, from 2001 to 2008, aiming to study the relationship between age and survival. We included variables related to patients, tumors, and types of treatment. Different sets of Cox models were used for survival analysis. Hazard ratios (HR) and 95%CI were calculated. The relationship between age and breast cancer survival did not change substantially in any of them. In the model that accounted for all variables, women aged 70 and older (HR = 1.51, 95%CI: 1.04-2.18), and 35 or younger (HR = 1.78, 95%CI: 1.05 3.01) had shorter cancer specific survival than patients aged between 36 and 69. In addition, older age, having at least one comorbidity, and being white were associated with a higher risk of dying from other causes. In conclusion, shorter breast cancer survival is expected among the youngest and oldest patients. PMID- 26375652 TI - [Domains of physical activity and education in Sao Paulo, Brazil: a serial cross sectional study in 2003 and 2008]. AB - This study aimed to estimate the prevalence of physical activity in different domains and the association with schooling, using a serial cross-sectional population-based design comparing data from two editions of a health survey in the city of Sao Paulo, Brazil. Participation included 1,667 adults in 2003 and 2,086 in 2008. Probabilistic sampling was performed by two-stage clusters. The long version of International Physical Activity Questionnaire (IPAQ) allowed evaluating multiple domains of physical activity. Poisson regression was used. Men were more active in their leisure time and at work and women in the home. Schooling was associated directly with leisure-time activity (2003 and 2008) and inversely with work-related physical activity (2003) for men and for women in housework. The studies showed that Brazilians with less schooling are becoming less active, so that intervention strategies should consider different educational levels. Interventions in the urban space and transportation can increase the opportunities for physical activity and broaden access by the population. PMID- 26375653 TI - Budget impact analysis of the percutaneous septal occluder for treatment of ostium secundum atrial septal defects in the Brazilian Unified National Health System. AB - The aim of this study was to perform a budget impact analysis on the adoption of percutaneous occlusion of ostium secundum atrial septal defects in the Brazilian Unified National Health System. Costs were collected using micro-costing technique from medical records for each treatment technique (conventional surgery versus percutaneous septal occluder) at a public federal hospital specialized in high-complexity cardiology. The analysis showed that expenditures associated with percutaneous occlusion were lower than with conventional surgery, and sensitivity analysis confirmed the cost reduction in several scenarios, showing a significant budget impact with a 30% adoption rate for the percutaneous occluder (savings of approximately 1.5 million dollars per year). The study indicates that the adoption of the percutaneous septal occluder would mean cost savings of approximately 3.5 million dollars for the Brazilian public health system. PMID- 26375654 TI - [Validity and utility of self-perceived need for dental treatment by adults and elderly]. AB - This study aimed to determine the validity of self-rated measures as an indicator of dental treatment needs in adults and the elderly. The sample consisted of individuals that participated in the National Oral Health Survey and the Survey on Oral Health Conditions in Minas Gerais State. Self-rated needs for dental treatment and total prostheses were compared to need based on dental examination, defined as the gold standard. The quality of measures was assessed by sensitivity, specificity, and predictive values. Sensitivity varied from 51% to 90%, and specificity from 56% to 90%. Positive predictive values were 11% to 95% and negative predictive values were 23% to 99%. Self-rated need for dental treatment in adults and for total prostheses in the elderly showed acceptable validity. Meanwhile, self-rated need for dental treatment in the elderly and for total prostheses in adults were not considered useful, due to their low performance. PMID- 26375655 TI - [Socio-demographic and health conditions associated with paid work in adults (50 69 years) in Greater Metropolitan Belo Horizonte, Minas Gerais State, Brazil]. AB - Factors associated with paid work were examined in a probabilistic sample of 3,320 adults (50-69 years) in Greater Metropolitan Belo Horizonte, Minas Gerais State, Brazil. Prevalence of paid work was 62.8% in men and 35.8% in women. For both men and women, paid work was positively associated with schooling and negatively associated with self-rated health. The probability of having paid work was higher for single women and those who knew someone that had suffered discrimination at the workplace. For men, prevalence of paid work varied from 67.2% in those with >= 8 years of schooling and better self-rated health, as compared to 37.8% in those with less schooling and poor self-rated health (PR = 0.56; 95%CI: 0.37-0.87). In women, the corresponding prevalence rates were 42.1% and 3.6% (PR = 0.09; 95%CI: 0.03-0.26). For women with little schooling and poor self-rated health, the likelihood of having paid work was ten times lower than for their male counterparts. PMID- 26375656 TI - The evolution of the socioeconomic gap in fertility among adolescents in Chile, 1990-2011. AB - For research and policy issues, it is very important to measure the evolution of socioeconomic differences in the adolescent fertility rate over time (AFER) in order to be able to provide a quantitative description of such an evolution. By combining well reputed Chilean data, this study computes a ratio of AFER (15-17 years-old) between the 30% of the population living in economically worst off areas (the numerator) against the corresponding 30% better off segment of the population (the denominator). This ratio of AFER by relative socioeconomic status shows a stable evolution from 1.45 in the year 1990 to 1.10 in 2011. Sexual initiation, whose association with AFER is well established, also shows a dropping ratio, from 1.24 in 1997 to 1.01 in 2012. The size of some dimensions of socioeconomic inequalities in adolescent fertility and sexual initiation has being decreasing between 1990 and 2011. This exercise shows that even in Chile, the most unequal country among the Organisation for Economic Co-operation and Development, there are some improvements in health inequality. PMID- 26375662 TI - Hemorrhagic shock caused by intramuscular hematoma of the pectoralis major after CPR. PMID- 26375660 TI - Creutzfeldt-Jakob Disease-Like Periodic Sharp Wave Complexes in Voltage-Gated Potassium Channel-Complex Antibodies Encephalitis: A Case Report. AB - INTRODUCTION: Voltage-gated potassium channel-complex antibodies (VGKC-cAbs) encephalitis, a treatable autoantibody encephalopathy, has been previously reported to clinically mimic sporadic Creutzfeldt-Jakob disease. Among available clinical clues to distinguish them, periodic sharp wave complexes, a typical finding in sporadic Creutzfeldt-Jakob disease, have never been reported in association with VGKC-cAbs encephalitis. CASE PRESENTATION: A 76-year-old man was transferred to a tertiary neurology center with a clinical history of 6-month weight loss, cognitive disturbance, and nonspecific generalized weakness. He had two seizures the month before transfer and then evolved to severe encephalopathy, requiring mechanical ventilation. Periodic sharp wave complexes every 1 to 2 seconds over slowed background were found on EEG, and MRI showed cerebellar and bifrontal cortical T2/FLAIR/DWI hypersignal without restricted diffusion on ADC mapping. Pancorporal positron emission tomography scan was negative. An immunotherapy trial did not improve the patient condition. Therefore, he died after life support withdrawal. Brain autopsy revealed mononuclear neocortex infiltrate without significant spongiosis, and the anti-VGKC test showed a seropositivity of 336 pmol/L (normal, 0-31), 3 month after the patient deceased. CONCLUSIONS: This is the first reported case of VGKC-cAbs encephalitis associated with periodic sharp wave complexes on EEG, which further confuse the differential diagnosis with sporadic Creutzfeldt-Jakob disease. However, the cortical DWI hypersignal without restriction seems to remain a way to discriminate these two entities appropriately, when present. These clues are of paramount importance because VGKC-cAbs encephalitis is a treatable disease. PMID- 26375661 TI - The impact of a pre-hospital critical care team on survival from out-of-hospital cardiac arrest. AB - AIM: To assess the impact of a pre-hospital critical care team (CCT) on survival from out-of-hospital cardiac arrest (OHCA). METHODS: We undertook a retrospective observational study, comparing OHCA patients attended by advanced life support (ALS) paramedics with OHCA patients attended by ALS paramedics and a CCT between April 2011 and April 2013 in a single ambulance service in Southwest England. We used multiple logistic regression to control for an anticipated imbalance of prognostic factors between the groups. The primary outcome was survival to hospital discharge. All data were collected independently of the research. RESULTS: 1851 cases of OHCA were included in the analysis, of which 1686 received ALS paramedic treatment and 165 were attended by both ALS paramedics and a CCT. Unadjusted rates of survival to hospital discharge were significantly higher in the CCT group, compared to the ALS paramedic group (15.8% and 6.5%, respectively, p<0.001). After adjustment using multiple logistic regression, the effect of CCT treatment was no longer statistically significant (OR 1.54, 95% CI 0.89-2.67, p=0.13). Subgroup analysis of OHCA with first monitored rhythm of ventricular fibrillation or pulseless ventricular tachycardia showed similar results. CONCLUSION: Pre-hospital critical care for OHCA was not associated with significantly improved rates of survival to hospital discharge. These results are in keeping with previously published studies. Further research with a larger sample size is required to determine whether CCTs can improve outcome in OHCA. PMID- 26375663 TI - Posttraumatic pulmonary hernia in child. PMID- 26375664 TI - Acute bilateral lower extremity arterial occlusion without risk factors or embolic source. AB - Acute arterial occlusion is an emergency condition that, if untreated, can lead to serious complications and potential limb amputation. Risk factors for acute arterial occlusion include aortic atherosclerosis, arterial trauma, recent myocardial infarction, and atrial fibrillation. We present a patient with no history of peripheral vascular disease who presented to the emergency department with severe bilateral leg pain. Computed tomography angiography was performed showing bilateral acute arterial occlusions. Emergent vascular surgery was performed to remove the thrombus and establish perfusion in order to prevent bilateral lower leg amputation. PMID- 26375665 TI - Immunohistochemical Study of Expression of Sohlh1 and Sohlh2 in Normal Adult Human Tissues. AB - The expression pattern of Sohlh1 (spermatogenesis and oogenesis specific basic helix-loop-helix 1) and Sohlh2 in mice has been reported in previous studies. Sohlh1 and Sohlh2 are specifically expressed in spermatogonia, prespermatogonia in male mice and oocytes of primordial and primary follicles in female mice. In this report, we studied the expression pattern of Sohlh1 and Sohlh2 in human adult tissues. Immunohistochemical staining of Sohlh1 and Sohlh2 was performed in 5 samples of normal ovaries and testes, respectively. The results revealed that Sohlh genes are not only expressed in oocytes and spermatogonia, but also in granular cells, theca cells, Sertoli cells and Leydig cells, and in smooth muscles of blood vessel walls. To further investigate the expression of Sohlh genes in other adult human tissues, we collected representative normal adult tissues developed from three embryonic germ layers. Compared with the expression in mice, Sohlhs exhibited a much more extensive expression pattern in human tissues. Sohlhs were detected in testis, ovary and epithelia developed from embryonic endoderm, ectoderm and tissues developed from embryonic mesoderm. Sohlh signals were found in spermatogonia, Sertoli cells and also Leydig cells in testis, while in ovary, the expression was mainly in oocytes of primordial and primary follicles, granular cells and theca cells of secondary follicles. Compared with Sohlh2, the expression of Sohlh1 was stronger and more extensive. Our study explored the expression of Sohlh genes in human tissues and might provide insights for functional studies of Sohlh genes. PMID- 26375666 TI - Evaluation of Multiband EPI Acquisitions for Resting State fMRI. AB - Functional magnetic resonance imaging (fMRI) and particularly resting state fMRI (rs-fMRI) is widely used to investigate resting state brain networks (RSNs) on the systems level. Echo planar imaging (EPI) is the state-of-the-art imaging technique for most fMRI studies. Therefore, improvements of EPI might lead to increased sensitivity for a large amount of studies performed every day. A number of developments to shorten acquisition time have been recently proposed and the multiband technique, allowing the simultaneous acquisition of multiple slices yielding an equivalent reduction of measurement time, is the most promising among them. While the prospect to significantly reduce acquisition time by means of high multiband acceleration factors (M) appears tempting, signal quality parameters and the sensitivity to detect common RSNs with increasing M-factor have only been partially investigated up to now. In this study, we therefore acquired rs-fMRI data from 20 healthy volunteers to systematically investigate signal characteristics and sensitivity for brain network activity in datasets with increasing M-factor, M = 2 - 4. Combined with an inplane, sensitivity encoding (SENSE), acceleration factor, S = 2, we applied a maximal acceleration factor of 8 (S2*M4). Our results suggest that an M-factor of 2 (total acceleration of 4) only causes negligible SNR decrease but reveals common RSN with increased sensitivity and stability. Further M-factor increase produced random artifacts as revealed by signal quality measures that may affect interpretation of RSNs under common scanning conditions. Given appropriate hardware, a mb-EPI sequence with a total acceleration of 4 significantly reduces overall scanning time and clearly increases sensitivity to detect common RSNs. Together, our results suggest mb-EPI at moderate acceleration factors as a novel standard for fMRI that might increase our understanding of network dynamics in healthy and diseased brains. PMID- 26375668 TI - Microbial diversity in deep-sea sediments from the Menez Gwen hydrothermal vent system of the Mid-Atlantic Ridge. AB - Deep-sea hydrothermal sediments are known to support remarkably diverse microbial consortia. Cultureindependent sequence-based technologies have extensively been used to disclose the associated microbial diversity as most of the microorganisms inhabiting these ecosystems remain uncultured. Here we provide the first description of the microbial community diversity found on sediments from Menez Gwen vent system. We compared hydrothermally influenced sediments, retrieved from an active vent chimney at 812 m depth, with non-hydrothermally influenced sediments, from a 1400 m depth bathyal plain. Considering the enriched methane and sulfur composition of Menez Gwen vent fluids, and the sediment physicochemical properties in each sampled area, we hypothesized that the site associated microbes would be different. To address this question, taxonomic profiles of bacterial, archaeal and micro-eukaryotic representatives were studied by rRNA gene tag pyrosequencing. Communities were shown to be significantly different and segregated by sediment geographical area. Specific mesophilic, thermophilic and hyperthermophilic archaeal (e.g., Archaeoglobus, ANME-1) and bacterial (e.g., Caldithrix, Thermodesulfobacteria) taxa were highly abundant near the vent chimney. In contrast, bathyal-associated members affiliated to more ubiquitous phylogroups from deep-ocean sediments (e.g., Thaumarchaeota MGI, Gamma and Alphaproteobacteria). This study provides a broader picture of the biological diversity and microbial biogeography, and represents a preliminary approach to the microbial ecology associated with the deep-sea sediments from the Menez Gwen hydrothermal vent field. PMID- 26375667 TI - Quantitative Genetics of Food Intake in Drosophila melanogaster. AB - Food intake is an essential animal activity, regulated by neural circuits that motivate food localization, evaluate nutritional content and acceptance or rejection responses through the gustatory system, and regulate neuroendocrine feedback loops that maintain energy homeostasis. Excess food consumption in people is associated with obesity and metabolic and cardiovascular disorders. However, little is known about the genetic basis of natural variation in food consumption. To gain insights in evolutionarily conserved genetic principles that regulate food intake, we took advantage of a model system, Drosophila melanogaster, in which food intake, environmental conditions and genetic background can be controlled precisely. We quantified variation in food intake among 182 inbred, sequenced lines of the Drosophila melanogaster Genetic Reference Panel (DGRP). We found significant genetic variation in the mean and within-line environmental variance of food consumption and observed sexual dimorphism and genetic variation in sexual dimorphism for both food intake traits (mean and variance). We performed genome wide association (GWA) analyses for mean food intake and environmental variance of food intake (using the coefficient of environmental variation, CVE, as the metric for environmental variance) and identified molecular polymorphisms associated with both traits. Validation experiments using RNAi-knockdown confirmed 24 of 31 (77%) candidate genes affecting food intake and/or variance of food intake, and a test cross between selected DGRP lines confirmed a SNP affecting mean food intake identified in the GWA analysis. The majority of the validated candidate genes were novel with respect to feeding behavior, and many had mammalian orthologs implicated in metabolic diseases. PMID- 26375669 TI - Elevated expression of Cripto-1 correlates with poor prognosis in hepatocellular carcinoma. AB - Cripto-1 could promote tumorigenesis in a wide range of carcinomas, yet little is known in hepatocellular carcinoma (HCC). The expression of Cripto-1 and MMP-9 were assessed by immunohistochemistry in 205 HCC specimens. The correlation between Cripto-1 and MMP-9, clinicopathological/prognostic value in HCC was examined. Cripto-1 overexpression was correlated with larger tumor, TNM stage, BCLC stage and tumor recurrence. In multivariate analyses, Cripto-1 was an independent predictor for overall survival (OS) and time to recurrence (TTR). Cripto-1 expression was increased in TNM and BCLC stage-dependent manner. Cripto 1 overexpression was associated with poor prognosis in patients subgroups stratified by tumor size, tumor differentiation, TNM and BCLC stage. In addition, Cripto-1 was positively correlated with MMP-9 among 205 HCC samples. Patients with Cripto-1 upregulation had poor OS and shorter TTR in low and high aggressiveness groups. Furthermore, Cripto-1 had predictive validity for early and late recurrence in HCC patients. Combination of Cripto-1 and serum AFP was correlated with OS and TTR. In conclusion, Cripto-1 overexpression contributes to aggressiveness and poor prognosis of HCC. Cripto-1/AFP expression could be a potential prognostic biomarker for survival in HCC patients. PMID- 26375670 TI - Double autophagy modulators reduce 2-deoxyglucose uptake in sarcoma patients. AB - RATIONALE: According to the metabolic symbiosis model, cancer stromal fibroblasts could be hijacked by surrounding cancer cells into a state of autophagy with aerobic glycolysis to help provide recycled nutrients. The purpose of this study was to investigate whether combined treatment with the autophagy inhibitor: hydroxychloroquine (HCQ) and the autophagy inducer: sirolimus (rapamycin, Rapa) would reduce glucose utilization in sarcoma patients. METHODS: Ten sarcoma patients who failed first-line treatment were enrolled in this study. They were treated with 1 mg of Rapa and 200 mg of HCQ twice daily for two weeks. The standardized uptake values (SUV) from pretreatment and posttreatment [18F] fluorodeoxyglucose positron emission tomography (FDG PET) scans were reviewed, and changes from the baseline SUVmax were evaluated. RESULTS: Based on FDG PET response criteria, six patients had a partial response; three had stable disease, and one had progressive disease. Nevertheless, none of them showed a reduction in tumor volume. The mean SUVmax reduction in the 34 lesions evaluated was - 19.6% (95% CI = -30.1% to -9.1%), while the mean volume change was +16.4% (95% CI = +5.8% to + 27%). Only grade 1 toxicities were observed. Elevated serum levels of lactate dehydrogenase were detected after treatment in most metabolic responders. CONCLUSIONS: The results of reduced SUVmax without tumor volume reduction after two weeks of Rapa and HCQ treatment may indicate that non-proliferative glycolysis occurred mainly in the cancer associated fibroblast compartment, and decreased glycolytic activity was evident from Rapa + HCQ double autophagy modulator treatment. PMID- 26375671 TI - Contrasting breast cancer molecular subtypes across serial tumor progression stages: biological and prognostic implications. AB - The relevance of the intrinsic subtypes for clinical management of metastatic breast cancer is not comprehensively established. We aimed to evaluate the prevalence and prognostic significance of drifts in tumor molecular subtypes during breast cancer progression. A well-annotated cohort of 304 women with advanced breast cancer was studied. Tissue microarrays of primary tumors and synchronous lymph node metastases were constructed. Conventional biomarkers were centrally assessed and molecular subtypes were assigned following the 2013 St Gallen guidelines. Fine-needle aspirates of asynchronous metastases were transcriptionally profiled and subtyped using PAM50. Discordant expression of individual biomarkers and molecular subtypes was observed during tumor progression. Primary luminal-like tumors were relatively unstable, frequently adopting a more aggressive subtype in the metastases. Notably, loss of ER expression and a luminal to non-luminal subtype conversion was associated with an inferior post-recurrence survival. In addition, ER and molecular subtype assessed at all tumor progression stages were independent prognostic factors for post recurrence breast cancer mortality in multivariable analyses. Our results demonstrate that drifts in tumor molecular subtypes may occur during tumor progression, conferring adverse consequences on outcome following breast cancer relapse. PMID- 26375672 TI - p73 regulates basal and starvation-induced liver metabolism in vivo. AB - As a member of the p53 gene family, p73 regulates cell cycle arrest, apoptosis, neurogenesis, immunity and inflammation. Recently, p73 has been shown to transcriptionally regulate selective metabolic enzymes, such as cytochrome c oxidase subunit IV isoform 1, glucose 6-phosphate dehydrogenase and glutaminase 2, resulting in significant effects on metabolism, including hepatocellular lipid metabolism, glutathione homeostasis and the pentose phosphate pathway. In order to further investigate the metabolic effect of p73, here, we compared the global metabolic profile of livers from p73 knockout and wild-type mice under both control and starvation conditions. Our results show that the depletion of all p73 isoforms cause altered lysine metabolism and glycolysis, distinct patterns for glutathione synthesis and Krebs cycle, as well as an elevated pentose phosphate pathway and abnormal lipid accumulation. These results indicate that p73 regulates basal and starvation-induced fuel metabolism in the liver, a finding that is likely to be highly relevant for metabolism-associated disorders, such as diabetes and cancer. PMID- 26375673 TI - Pre-clinical evidence of PIM kinase inhibitor activity in BCR-ABL1 unmutated and mutated Philadelphia chromosome-positive (Ph+) leukemias. AB - We investigated the efficacy of targeting the PIM kinase pathway in Philadelphia chromosome-positive (Ph+) leukemias. We provide evidence that inhibition of PIM, with the pan-PIM inhibitor SGI-1776, results in suppression of classic PIM effectors and also elements of the mTOR pathway, suggesting interplay between PIM and mTOR signals. Our data demonstrate that PIM inhibition enhances the effects of imatinib mesylate on Ph+ leukemia cells. We also found that PIM inhibition results in suppression of leukemic cell proliferation and induction of apoptosis of Ph+ leukemia cells, including those resistant to imatinib mesylate. Importantly, inhibition of PIM results in enhanced suppression of primary leukemic progenitors from patients with CML. Altogether these findings suggest that pharmacological PIM targeting may provide a unique therapeutic approach for the treatment of Ph+ leukemias. PMID- 26375674 TI - Pretreatment with VEGF(R)-inhibitors reduces interstitial fluid pressure, increases intraperitoneal chemotherapy drug penetration, and impedes tumor growth in a mouse colorectal carcinomatosis model. AB - Cytoreductive surgery combined with intraperitoneal chemotherapy (IPC) is currently the standard treatment for selected patients with peritoneal carcinomatosis of colorectal cancer. However, especially after incomplete cytoreduction, disease progression is common and this is likely due to limited tissue penetration and efficacy of intraperitoneal cytotoxic drugs. Tumor microenvironment-targeting drugs, such as VEGF(R) and PDGFR inhibitors, can lower the heightened interstitial fluid pressure in tumors, a barrier to drug delivery. Here, we investigated whether tumor microenvironment-targeting drugs enhance the effectiveness of intraperitoneal chemotherapy. A mouse xenograft model with two large peritoneal implants of colorectal cancer cells was developed to study drug distribution and tumor physiology during intraperitoneal Oxaliplatin perfusion. Mice were treated for six days with either Placebo, Imatinib (anti-PDGFR, daily), Bevacizumab (anti-VEGF, twice) or Pazopanib (anti-PDGFR, -VEGFR; daily) followed by intraperitoneal oxaliplatin chemotherapy. Bevacizumab and Pazopanib significantly lowered interstitial fluid pressure, increased Oxaliplatin penetration (assessed by laser ablation inductively coupled plasma mass spectrometry) and delayed tumor growth of peritoneal implants (assessed by MRI). Our findings suggest that VEGF(R)-inhibition may improve the efficacy of IPC, particularly for patients for whom a complete cytoreduction might not be feasible. PMID- 26375675 TI - Correction: Selective photoregulation of the activity of glycogen synthase and glycogen phosphorylase, two key enzymes in glycogen metabolism. AB - Correction for 'Selective photoregulation of the activity of glycogen synthase and glycogen phosphorylase, two key enzymes in glycogen metabolism' by Mireia Diaz-Lobo, et al., Org. Biomol. Chem., 2015, 13, 7282-7288. PMID- 26375676 TI - Inhibition of Excessive Cell Proliferation by Calcilytics in Idiopathic Pulmonary Arterial Hypertension. AB - Idiopathic pulmonary arterial hypertension (IPAH) is a rare and progressive disease of unknown pathogenesis. Vascular remodeling due to excessive proliferation of pulmonary arterial smooth muscle cells (PASMCs) is a critical pathogenic event that leads to early morbidity and mortality. The excessive cell proliferation is closely linked to the augmented Ca2+ signaling in PASMCs. More recently, we have shown by an siRNA knockdown method that the Ca2+-sensing receptor (CaSR) is upregulated in PASMCs from IPAH patients, involved in the enhanced Ca2+ response and subsequent excessive cell proliferation. In this study, we examined whether pharmacological blockade of CaSR attenuated the excessive proliferation of PASMCs from IPAH patients by MTT assay. The proliferation rate of PASMCs from IPAH patients was much higher (~1.5-fold) than that of PASMCs from normal subjects and patients with chronic thromboembolic pulmonary hypertension (CTEPH). Treatment with NPS2143, an antagonist of CaSR or calcilytic, clearly suppressed the cell proliferation in a concentration dependent manner (IC50 = 2.64 MUM) in IPAH-PASMCs, but not in normal and CTEPH PASMCs. Another calcilytic, Calhex 231, which is structurally unrelated to NPS2143, also concentration-dependently inhibited the excessive proliferation of IPAH-PASMCs (IC50 = 1.89 MUM). In contrast, R568, an activator of CaSR or calcimimetic, significantly facilitated the proliferation of IPAH-PASMCs (EC50 = 0.33 MUM). Similar results were obtained by BrdU incorporation assay. These results reveal that the excessive PASMC proliferation was modulated by pharmacological tools of CaSR, showing us that calcilytics are useful for a novel therapeutic approach for pulmonary arterial hypertension. PMID- 26375677 TI - An Experimental Study on the Use of Calcium Alginate to Heal Colonic Anastomoses. AB - BACKGROUND: Anastomotic leak is considered the major complication following abdominal surgery. In recent years, the use of a variety of sealing materials for the prevention of leaks has been analyzed. Different biomaterials have been employed as scaffolds to favour tissue repair and regeneration. Among these materials we must mention alginate, a natural polymer with different applications as temporary supporting matrix. The aim of the present study is to evaluate the behavior of both alginate-impregnated sutures and lyophilized alginate sponges in the healing process of colonic anastomes using an experimental animal model. MATERIAL AND METHODS: A preliminary study was undertaken to select the adequate scaffold. Animals (n = 45) were distributed into three groups: control (colonic anastomosis using non-continuous 5-0 Polyglactin 910 suture), suture (colonic anastomosis using suture impregnated with alginate gel at 4%) and sponge (colonic anastomosis using suture reinforced with lyophilized alginate sponge). The macroscopic and histological variables were assessed at 4, 8 and 12 days after surgical intervention. RESULTS: No statistically significant differences have been observed between the groups during the analysis of macroscopic variables. Animals with sponge implantation showed a greater degree of epithelial reepithalization, less acute and chronic inflammation and greater collagen deposit. CONCLUSIONS: The use of lyophilized alginate sponges to reinforce colonic anastomoses in an animal model reduces inflammation and promotes the earlier formation of greater collagen deposits without increasing the number of adhesions or the incidence of stenosis. PMID- 26375678 TI - Author Credit for Transdisciplinary Collaboration. AB - Transdisciplinary collaboration is the key for innovation. An evaluation mechanism is necessary to ensure that academic credit for this costly process can be allocated fairly among coauthors. This paper proposes a set of quantitative measures (e.g., t_credit and t_index) to reflect authors' transdisciplinary contributions to publications. These measures are based on paper-topic probability distributions and author-topic probability distributions. We conduct an empirical analysis of the information retrieval domain which demonstrates that these measures effectively improve the results of harmonic_credit and h_index measures by taking into account the transdisciplinary contributions of authors. The definitions of t_credit and t_index provide a fair and effective way for research organizations to assign credit to authors of transdisciplinary publications. PMID- 26375679 TI - Identification of a Novel Human Papillomavirus, Type HPV199, Isolated from a Nasopharynx and Anal Canal, and Complete Genomic Characterization of Papillomavirus Species Gamma-12. AB - The novel human papillomavirus type 199 (HPV199) was initially identified in a nasopharyngeal swab sample obtained from a 25 year-old immunocompetent male. The complete genome of HPV199 is 7,184 bp in length with a GC content of 36.5%. Comparative genomic characterization of HPV199 and its closest relatives showed the classical genomic organization of Gammapapillomaviruses (Gamma-PVs). HPV199 has seven major open reading frames (ORFs), encoding five early (E1, E2, E4, E6, and E7) and two late (L1 and L2) proteins, while lacking the E5 ORF. The long control region (LCR) of 513 bp is located between the L1 and E6 ORFs. Phylogenetic analysis additionally confirmed that HPV-199 clusters into the Gamma PV genus, species Gamma-12, additionally containing HPV127, HV132, HPV148, HPV165, and three putative HPV types: KC5, CG2 and CG3. HPV199 is most closely related to HPV127 (nucleotide identity 77%). The complete viral genome sequence of additional HPV199 isolate was determined from anal canal swab sample. Two HPV199 complete viral sequences exhibit 99.4% nucleotide identity. To the best of our knowledge, this is the first member of Gamma-PV with complete nucleotide sequences determined from two independent clinical samples. To evaluate the tissue tropism of the novel HPV type, 916 clinical samples were tested using HPV199 type-specific real-time PCR: HPV199 was detected in 2/76 tissue samples of histologically confirmed common warts, 2/108 samples of eyebrow hair follicles, 2/137 anal canal swabs obtained from individuals with clinically evident anal pathology, 4/184 nasopharyngeal swabs and 3/411 cervical swabs obtained from women with normal cervical cytology. Although HPV199 was found in 1.4% of cutaneous and mucosal samples only, it exhibits dual tissue tropism. According to the results of our study and literature data, dual tropism of all Gamma-12 members is highly possible. PMID- 26375681 TI - Reported Child Health Status, Hispanic Ethnicity, and Language of Interview: United States, 2011-2012. AB - OBJECTIVES: This report has three objectives: a) to describe the reported health status of four subgroups of school-age children: Hispanic children with a Spanish interview (Hispanic-Spanish interview), Hispanic children with an English interview (Hispanic-English interview), non-Hispanic black children, and non Hispanic white children; b) to describe selected characteristics of children in the four subgroups; and c) to consider whether the characteristics of children account for subgroup variations in reported health status. DATA SOURCE AND METHODS: Data from the 2011-2012 National Survey of Children's Health were used to describe the health status of children aged 5-17 years using three categories: a) poor or fair, b) good, and c) very good or excellent health. The reported health status of children in the four subgroups was examined using multinomial logistic regression, controlling for the effects of demographic and socioeconomic characteristics and a measure of acculturation. RESULTS: Compared with children in the other subgroups, Hispanic-Spanish interview children were more likely to have reports of poor or fair health (10.6% compared with 1.8%-4.4%) and good health (39.7% compared with 7.7%- 14.4%). Controlling for demographic and socioeconomic characteristics and a measure of acculturation eliminated the subgroup differences in poor or fair health, but not good health. Even after adjustment for confounders, Hispanic-Spanish interview children more often were reported to have good health rather than very good or excellent health compared with children in the other subgroups. CONCLUSIONS: Worse reported health status of Hispanic-Spanish interview children, compared with children in other subgroups, could not be explained completely by the confounders in the analysis. Additional research is needed to determine whether the worse reported health status of Hispanic children with Spanish interviews reflects the actual health conditions of these children or difficulties in translating the health status question. PMID- 26375680 TI - Complex Population Structure and Virulence Differences among Serotype 2 Streptococcus suis Strains Belonging to Sequence Type 28. AB - Streptococcus suis is a major swine pathogen and a zoonotic agent. Serotype 2 strains are the most frequently associated with disease. However, not all serotype 2 lineages are considered virulent. Indeed, sequence type (ST) 28 serotype 2 S. suis strains have been described as a homogeneous group of low virulence. However, ST28 strains are often isolated from diseased swine in some countries, and at least four human ST28 cases have been reported. Here, we used whole-genome sequencing and animal infection models to test the hypothesis that the ST28 lineage comprises strains of different genetic backgrounds and different virulence. We used 50 S. suis ST28 strains isolated in Canada, the United States and Japan from diseased pigs, and one ST28 strain from a human case isolated in Thailand. We report a complex population structure among the 51 ST28 strains. Diversity resulted from variable gene content, recombination events and numerous genome-wide polymorphisms not attributable to recombination. Phylogenetic analysis using core genome single-nucleotide polymorphisms revealed four discrete clades with strong geographic structure, and a fifth clade formed by US, Thai and Japanese strains. When tested in experimental animal models, strains from this latter clade were significantly more virulent than a Canadian ST28 reference strain, and a closely related Canadian strain. Our results highlight the limitations of MLST for both phylogenetic analysis and virulence prediction and raise concerns about the possible emergence of ST28 strains in human clinical cases. PMID- 26375682 TI - Cellular Defense Enzyme Drives Exceptionally High Rate of Mutation in HIV. AB - HIV-1 is already known to have an extremely fast mutation rate, but a new study shows it to be more than two orders of magnitude higher than previously believed, and that this is largely due to host cytidine deaminases. Read the Research Article. PMID- 26375685 TI - [Takotsubo cardiomyopathy - what has changed - editorial]. PMID- 26375684 TI - Pharmacokinetic study and clinical evaluation of a slow-release 5-fluorouracil implant in pancreatic cancer patients. AB - The aim of this research was to study the pharmacokinetic characteristics of a slow-release 5-fluorouracil implant as well as to evaluate the clinical drug activity of this preparation in pancreatic cancer patients. Pharmacokinetic characteristics of the slow-release 5-fluorouracil implant were evaluated by examining the half-life time (T1/2) and apparent volume of distribution (Vd) in pancreatic cancer patients; the slow-release 5-fluorouracil implant was administered through interstitial chemotherapy (tumor interstitium implantation). In the drug activity study, 36 locally advanced unresectable pancreatic cancer patients were divided randomly into an experimental treatment group (n=18) and a standard treatment group (n=18). The experimental treatment group was treated with interstitial chemotherapy of a slow-release 5-fluorouracil implant combined with systemic chemotherapy of gemcitabine; the standard treatment group was treated with systemic chemotherapy of gemcitabine. An internal drainage procedure was used when biliary and/or gastrointestinal tract obstruction occurred in the two groups. Clinical benefit response, including pain (visual analogue scale), analgesic drug use, general conditions (Karnofsky performance score), weight changes, and survival status, was observed. T1/2 of the slow-release 5 fluorouracil implant was 5475.8+/-136.4 min, whereas Vd was 45275.0+/-1028.6 l. Clinical benefit response in the experimental treatment group was better than that in the standard treatment group. The experimental treatment group had longer median survival time compared with the standard treatment group. The slow-release 5-fluorouracil implant could deliver drugs mainly in the regional area of the tumor and prolong the drug action time; interstitial chemotherapy of a 5 fluorouracil implant combined with systemic chemotherapy of gemcitabine could improve the quality of life and survival status of pancreatic cancer patients. The method was promising and worthy of in-depth investigations. PMID- 26375683 TI - Selectivity in acquired prosopagnosia: The segregation of divergent and convergent operations. AB - Face recognition can be viewed as part of a divergent set of operations in object recognition, in which information from common low-level visual mechanisms feeds forward into increasingly specialized processes for different object types. This divergence may also involve hemispheric specialization, notably for faces in the right and words in the left hemisphere. However, in person recognition, face processing is one of a set of sensory inputs that converge upon access to stored information about people. We review the literature and evidence from a cohort of acquired prosopagnosic subjects, on three issues concerning selectivity. First, we review the data on object recognition in prosopagnosia, and recent evidence that, after adjusting for pre-morbid car expertise, impairments of car identification are common in our cohort, particularly among car experts. Second, we review the data on word processing in prosopagnosia. In our cohort we show that the word-length effect in single word reading is normal after right-sided lesions, but the discrimination of font and handwriting is impaired in most of our subjects, regardless of lesion location. Third, we discuss the status of voice recognition in prosopagnosia, and show that in our cohort, right anterior temporal lesions do not impair this function, but bilateral ones do. Together, these findings suggest that the processes for faces, cars and visual text involve either the same neural resources or parallel processes in close proximity. Voice and face processing remain distinct in our subjects, and confirm that right anterior temporal lesions cause an associative prosopagnosia rather than a multi modal person recognition syndrome. PMID- 26375686 TI - [Risk factors of thyroid carcinoma - editorial]. PMID- 26375687 TI - [Takotsubo cardiomyopathy, clinical experience with the disease and one-year prognosis of patients]. AB - INTRODUCTION: Takotsubo cardiomyopathy (TCM) is a rare cardiac disease. In the acute phase it may imitate acute myocardial infarction of the anterior wall with ST elevations. This can be complicated by ventricular fibrilation or heart failure. The aim of this study is to show the characteristics of patients with takotsubo cardiomyopathy, the one year outcome and the application of magnetic resonance imaging of the heart in the diagnosis of this disease. METHODS: Forty seven patients with takotsubo cardiomyopathy were enrolled in this study. Severe stenosis of coronary arteries was excluded by selective coronarography. In twelve patients the magnetic resonance imaging of the myocardium was performed. The patients were observed for at least 12 months. RESULTS: 89.4 % of takotsubo patients were women. Average of age was 62.3 +/- 11.1 years. We found obvious stress factors in 18 patients (38.3 %). Many patients suffered from thyroid disorders, psychiatric, lung or allergic diseases. Thirty nine patients (83.0 %) had the apical and eight the midventricular type of takotsubo cardiomyopathy. In 42 patients (89.4 %) developed systolic left ventricular dysfunction and four patients (8.5 %) were in cardiogenic shock. Four patients (8.5 %) manifested ventricle fibrilation. One patient (2.1 %) had recurring takotsubo cardiomyopathy. CONCLUSION: Left ventricle function is mostly recovered in patients with takotsubo cardiomyopathy, but the acute phase can be complicated by cardiogenic shock or ventricular fibrilation. Magnetic resonance imaging of the heart is indicated in some patients to differentiate this cardiomyopathy from ischemic or inflammatory etiology. PMID- 26375688 TI - [Rituximab infusion-related toxicity in patients with chronic lymphocytic leukemia]. AB - BACKGROUND AND AIMS: Rituximab in combination with chemotherapy is an effective treatment of patients (pts) with chronic lymphocytic leukemia (CLL). The most frequent adverse event of rituximab is infusion-related toxicity, e.g. cytokine release syndrome that occurs usually during the first infusion. However, there is scarce data on feasibility and tolerability of rituximab infusions in CLL outside clinical trials. Therefore, we performed a single-center retrospective analysis of the frequency of rituximab infusion-related adverse events during the first- and the second line CLL treatment administered in the routine practice. We also analyzed its relation to parameters of tumor load and possible association with treatment efficacy. The safety of rapid infusion of rituximab in CLL pts was also evaluated. PATIENTS AND METHODS: We analyzed 108 pts with CLL treated with rituximab-containing regimens between March 2005 and May 2011 at our institution. The most common first-line regimens (n = 66, 47 males, median age 63 years) were FCR (43 pts) and low-dose FCR (13 pts); 10 pts were treated by other protocols. Forty-two pts (32 males, median age, 65 years) underwent second line treatment: 18 pts rituximab-dexamethasone, 7 pts FCR, 7 pts low-dose FCR and 10 pts other regimens. Intravenous hydration (2000 ml daily on days 0 and 1 of cycle), allopurinol 300-600 mg p. o. daily and premedication with methylprednisolone 80 mg i. v., acetaminophen 1000 mg p. o. and bluepine 1 mg i. v. were administered before rituximab infusion. Rituximab was given by fractionated infusion (100 mg for 2 hours, then if tolerated well, the rest of the dose with infusion rate escalation from 100 mg/hour up to 400 mg/hour) at the dose of 375 mg/m2 in the first cycle. Subsequent doses (500 mg/m2) were administered by rapid-infusion protocol. RESULTS: Rituximab infusion-related toxicity occurred in 32 % pts (n = 21) during the first line treatment and 19% pts (n = 8) during the second line treatment. Adverse events were predominantly mild and NCI CTCAE grade III/IV occurred rarely (3% in the first line, 2% in the second line). Infusion toxicity manifested predominantly as rigors, chills, fever and hypotension. All patients with adverse events could finish rituximab infusion as initially planned on the same day. Treatment response analysis did not demonstrate statistically significant differences between patients with and without rituximab infusion toxicity. Patients who developed rituximab infusion toxicity had higher absolute lymphocyte count (first line, 87 vs 56 * 109/l, p = 0.21; second line, 101 vs 14 * 109/l, p = 0.043). At the median follow-up of 36 months, there were no statistically significant differences in PFS or OS in both cohorts. CONCLUSIONS: Rituximab infusion-related toxicity in pts with CLL is relatively frequent (32%). However, occurrence of infusion-related symptoms can be reduced by proper premedication and severe adverse events are uncommon. In our experience, all patients were able to receive the planned dose of rituximab. Subsequent doses of rituximab could be safely administered by rapid-infusion protocol. We did not find statistically significant association between rituximab infusion toxicity and effectiveness of treatment. PMID- 26375689 TI - [Cardiovascular effects of GLP-1 receptor agonist treatment: focus on liraglutide]. AB - Cardiovascular risk reduction is the major aim of type 2 diabetes mellitus treatment. The effects of various antidiabetics on the cardiovascular complications are currently under careful scrutiny. Incretin-based therapy that utilizes the effects of glucagon-like peptide 1 (GLP-1) or stimulation of its receptor by GLP-1 receptor agonists represents one of the most promising approaches from the potential cardiovascular risk reduction point of view. Experimental studies have shown that the GLP-1 and GLP-1 agonists treatment improves endothelial function, decrease blood pressure and protects myocardium during experimentally-induced ischemia. Clinical studies with GLP-1 receptor agonists consistently show that, in addition to good antidiabetic efficacy, its long-term administration decreases blood pressure, body weight and improves circulating lipid levels while slightly increasing heart rate. In this paper, we focus on the cardiovascular effects of GLP-1 receptor agonist liraglutide. Preliminary analyses of cardiovascular complications in phase III trials with liraglutide indicate its good cardiovascular safety. A possibility of cardioprotective effects of liraglutide remains still open and is currently studied within a prospective cardiovascular trial LEADER. PMID- 26375690 TI - [Transcatheter aortic valve implantation - diagnostic, procedure and outcomes]. AB - Transcatheter aortic valve implantation (TAVI) is an interventional method for the treatment of severe aortic stenosis. TAVI is indicated in patients who have been identified by the heart team as surgically inoperable or operable at very high risk. The advantage is minimal invasive approach with the absence of sternotomy and extracorporeal blood circulation. Interventional procedure does not allow direct visualization of the anatomical relations at the site of the final valve position (aortic anulus). For this reason it is essential to ensure appropriate view by high quality imaging methods. A standard method for the evaluation of the anatomical relations before TAVI is multidetector computed tomography (MDCT) with 3D reconstruction. In the future, the MDCT would be replaced by three-dimensional transesophageal echocardiography (3D TEE), which does not require ionizing radiation, there is no postcontrast nephropathy and hypersensitive reaction to iodine compared to MDCT. Furthermore, it provides direct measurements during the procedure and ensures easier and cheaper dispensarisation of the patients. A multicenter randomized PARTNER trial clearly demonstrated significant benefits of inoperable patients with severe aortic stenosis treated by TAVI. Recently published CoreValve US Pivotal randomized trial demonstrated higher efficiency and safety of TAVI in direct comparison with surgical treatment. The aim of this review is to provide current knowledge of TAVI, preparation of the patients before the intervention, the process of intervention, dispensarisation, as well as affecting the quality of patients life. PMID- 26375691 TI - [Hepatorenal syndrome - pathophysiology, diagnosis and treatment]. AB - Hepatorenal syndrome (HRS) is a life-treating complication of liver diseases. This functional kidney impairment is classified into acute (type I) and chronic (type II) types and is connected with high mortality. Treatment options are limited, but administration of vasoconstrictors (terlipressin), albumin and portosystemic shunt may improve their prognosis. Liver transplantation is the most effective method for these patients. Authors want to present recent data relating to HRS, including therapeutic recommendations. PMID- 26375692 TI - [Risk factors of thyroid carcinoma]. AB - Thyroid cancer is one of the worlds fastest growing tumor incidences. The number of new cases has particularly increased in differentiated papillary thyroid carcinoma. In the Czech Republic it is documented that the incidence of thyroid cancer continues to grow, since 1980 has increased four times. The Czech Republic has a higher incidence than most other European countries and at the same time is a country with average and declining mortality from this disease. This review summarizes the known risk factors that may contribute to the formation and rise of thyroid carcinomas. PMID- 26375694 TI - [Not Available]. PMID- 26375693 TI - [Erectile dysfunction as the first sign of systemic vascular diseases and of organovascular arterial ischemic diseases. Guidelines and Challenge of the Angiology section of Slovak Medical Chamber (AS SMC, 2015)]. AB - Erectile dysfunction is a highly prevalent and progressive condition affecting the quality of life of man and his sexual partner. Evidence is accumulating in favour of erectile dysfunction as a sign of a genitovascular disease (GVD) in the majority of patients. Erectile dysfunction may be considered as the clinical manifestation of a organovascular disease affecting penis (male genitovascular disease - MGVD) as well as angina pectoris is the typical manifestation of a vascular disease affecting coronary arteries of a heart (cardiovascular disease - CVD). Several studies confirm the assumption that erectile dysfunction symptoms were found to come prior to cardiovascular disease symptoms in 60-95 % of CVD patients with mean interval of 2-3 years and likewise of all organovascular diseases (OVD). Four potent selective PDE5Is have been approved by the EMA for the treatment of erectile dysfunction. Physicians should systematically look for erectile dysfunction in any male with vascular risk factors. PMID- 26375695 TI - [Cannabis - therapy for the future?]. AB - Despite all the progress achieved in the treatment of chronic gastrointestinal diseases, in some patients the treatment does not reach long-term optimum effectiveness. Therefore a number of patients have turned to complementary and alternative medicine (CAM). Of the different types of CAM patients with GIT diseases tend to prefer in particular homeopathy, acupuncture and not least phytotherapy, where therapeutic use of cannabis may also be included. The pathophysiological basis of therapeutic effect of curative cannabis has not been fully clarified so far. Many scientists in many fields of medicine and pharmacology have been engaged in the study of effects of cannabinoids on the body since the beginning of the 20th century with the interest significantly increasing in the 1980s. The discovery of CB receptors (1988) and endogenous molecules which activate these receptors (1992) led to the discovery of the endocannabinoid system. Pharmacological modulation of the endogenous cannabinoid system offers new therapeutic possibilities of treatment of many illnesses and symptoms including the GIT disorders, including of nausea, vomiting, cachexia, IBS, Crohns disease and some other disorders. Cannabinoids are attractive due to their therapeutic potential - they affect a lot of symptoms with minimum side effects. Experience of patients with GIT disorders show that the use of cannabis is effective and helps in cases where the standard therapy fails. PMID- 26375696 TI - [New trends in treatment of non-variceal bleeding in the upper gastrointestinal tract]. AB - Acute upper gastrointestinal tract bleeding is a life-threatening incident in which a right diagnostic and therapeutic approach is necessary. Beside the standards in endoscopic hemostasis (adrenalin injection, hemostatic clips) there are some new technologies in endoscopic hemostasis. PMID- 26375697 TI - [Home nutrition care in the Czech Republic]. AB - Home artificial nutrition includes application of enteral and parenteral nutrition in home environment, in cases of natural nutrition access failure. Home enteral nutrition uses various modality and ways, when persist the functional bowel. Chronic intestinal failure indicates dependence of home parenteral nutrition and is aplicated with central venous accesses. Home artificial nutrition improves patient's quality of life and is more economical compared with hospital care. PMID- 26375698 TI - [Vitamin D - old substance in new perspectives]. AB - Receptors for vitamin D are present almost in all body tissues. Vitamin D does not only act as a regulator of calcium and phosphorus metabolism, but also a substance which modulates the immunity system function, regulates cell proliferation. Genetic, epidemiological and experimental data indicate a possible role of vitamin D deficiency in the development of some diseases, mainly of autoimmune diseases and tumours. The benefit of curative intake of vitamin D has so far not been proven. There is no reason why the deficiency of vitamin D should not be covered. The substitution should start with the replenishment of the lacking amount of vitamin D (which may even be several hundred thousand units) and involve ongoing intake of the recommended substitution dose of 800-1000 vitamin D units per day. PMID- 26375699 TI - [Possible endoscopic solutions of polypoid and non-polypoid lesions in the colon]. AB - Colorectal cancer (CRC) is one of the most frequent malignant diseases in the Czech Republic. Almost 70 % of CRC develop based on adenomatous polyps, 30 % arise de novo. The pathogenesis of development of colorectal cancer confirms an adenoma to carcinoma sequence, based on the gradually developing mutations of oncogenes and suppressor genes. By removing the adenomatous mucosal neoplasia the pathway of CRC development is cut off, which is the practical goal of the screening programme. To meet the goals of the preventive programme the gastroenterologists performing endoscopy must be appropriately trained and experienced in the detection of and procedures of removing mucosal neoplasias. Surface mucosal neoplasias are morphologically divided based on the Paris and Japanese classification into 2 basic types: protruding type I, whose height is greater than 2.5 mm above the level of the surrounding mucous membrane, and flat type II, whose height is smaller than 2.5mm. We have the following procedures available for endoscopic removing of surface mucosal lesions: loop polypectomy, endoscopic mucosal resection and endoscopic submucosal dissection. The choice of method depends on the lesion morphology. Benign mucosal lesions (adenoma, hyperplastic polyp) can only be treated endoscopically. Non-invasive malignant mucosal lesions limited to mucosa can also be treated endoscopically, invasive cancers penetrating into submucosa (malignant polyp, T1N0M0) are treated based on the definitive histological finding, and on meeting Morsons criteria the endoscopic removal can be seen as curative. The problem of flat malignant mucosal lesions is more complex and in most cases, when cancerous cells penetrate into submucosa, endoscopic resection cannot be performed and surgical solution follows. PMID- 26375700 TI - [Ordinary disease - appendicitis]. AB - Appendicitis is the most common abdominal emergency. While the clinical diagnosis may be easy in patients who present with classic signs and symptoms. Atypical presentations may result in diagnostic embarrassment and delay in treatment. Typical sign is abdominal pain. Furthermore, it can be nausea, vomiting and anorexia. Abdominal examination reveals localised tenderness and muscular rigidity in the right lower abdominal quadrant. Laboratory data usually reveal an elevated leukocytosis with a left shift and elevated C-reactive protein. To establish the diagnosis greatly help native abdominal X-ray, ultrasound or CT. In 1889, an appendectomy was accepted as the standard treatment, because they save lives and since then dictum: removal of the inflamed appendix changed, it is necessary! PMID- 26375701 TI - [Does "LDL hypothesis" also apply to patients with diabetes?]. AB - The basic symptom of diabetes mellitus is hyperglycemia. However the increased cardiovascular risk in patients with both type 1 and type 2 diabetes mellitus has a multifactorial etiology. Concurrent negative effects of hyperglycemia, hypertension and hyperlipidemia on the vascular system reinforce one another. Consistent prevention of cardiovascular risk parameters in patients with type 2 diabetes mellitus (DM2T) has brought significant decline in mortality and morbidity due to cardiovascular diseases. Still there is "residual risk" remaining. The full use of the potential of statins and their combination with ezetimibe may lower the CV risk even more and extend the life of patients with DM2. The importance of an intervention by means of PCSK9 inhibitors for the cardiovascular risk reduction in patients with diabetes mellitus is the subject of study. PMID- 26375702 TI - [Lowering of blood pressure - by treatment of other risk factors]. AB - Reaching the target value of blood pressure is still a big problem. A mere 30 % of treated hypertensives reach blood pressure values < 140/90 mm Hg. Hypertensive patients often exhibit further risk factors - diabetes mellitus, dyslipoproteinemia, excess weight and obesity, all of which are included in the definition of metabolic syndrome. The cardiovascular risks associated with the individual risk factors are not summed, they are multiplied. Unfortunately, the individual risk factors have been treated separately until now. However, there is an effort aimed at treating individual risk factors in the way that may positively affect others. The study focuses on the treatment of type 2 diabetes mellitus, dyslipidemia, excess weight and obesity taking account of possible influencing of blood pressure values. PMID- 26375703 TI - [How to treat dyslipidemia in patients with metabolic syndrome]. AB - Typical feature of dyslipidemia in patients with metabolic syndrome is increase triglycerides, decrease HDL-cholesterol and presence of small atherogenic LDL particle; nevertheless majority of patients do not reach target level of LDL cholesterol for their risk category as well. An essential part of treatment should be non-pharmacological approach - lifestyle changes (weight loss, change in eating habits, increased physical activity). In patients in primary prevention without diabetes decision about pharmacotherapy depend on their risk of fatal cardiovascular events in the perspective of 10 years (table SCORE). In diabetic patients and in patients in secondary prevention is pharmacotherapy indicated, unless their LDL-cholesterol does not reach its target values. The primary goal of treatment is LDL-cholesterol, so pharmacotherapy should be started with statins. If the target of LDL-cholesterol is reached and hypertriglyceridemia and/or low HDL-cholesterol persist, it is recommended to add fenofibrate to statin. PMID- 26375704 TI - [AB0 incompatible kidney transplantation - first experiences]. AB - Living donor AB0 incompatible kidney transplantation represents a new tool how to improve the access to transplantation. Majority of European protocols are based on desensitization with rituximab, triple drug immunosuppression, intravenous immunoglobulins and specific immunoads option (IA) which eliminates isohaemaglutinins. AB0i kidney transplant program was initiated in our centre in 2011 and 21 patients have received grafts from incompatible donors until recently. Highest accepted isohaemaglutinins titers before rituximab were 1 : 64 and corresponding pretransplant immunoadsorption procedures varied from 2 to 9. In 5 patients 1-2 IA procedures were performed also after transplantation. With the advent of paired exchange program the AB0i transplantation is offered to patients with unsuccessful matching run or with aim to improve HLA match between donor and recipient. The main complications were postoperative bleeding and urinary tract infections in patients at risk. Majority of protocol biopsies exhibited positivity of C4d staining. Neither graft loss nor patient death were noticed. PMID- 26375705 TI - [Pancreas transplantation: State of the art and future prospects]. AB - During the past 30 years pancreas transplantation evolved into a routine procedure especially suitable for type 1 diabetic recipients undergoing simultaneously kidney transplantation significantly improving quality of life and life expectancy as compared with kidney only recipients. It provides insulin independence with near-normal glucose control without special dietary restriction, freedom from hypoglycemia and chance for halting or regression of microangiopathic diabetes complications. As a separate procedure, pancreas transplantation is carried out mainly in selected subjects suffering from severe hypoglycemic episodes and impaired hypoglycemia awareness or as a subsequent procedure in type 1 diabetic kidney recipients from both cadaveric or living donors. Five-year insulin independence rate following combined pancreas and kidney, pancreas only and pancreas after kidney procedures currently exceed 75, 50 and 62 %, respectively. Though the outcomes still continue to improve, the rate of pancreas transplants has reached a plateau in several European countries or even declines in the United States. Main reasons for that include fewer referrals from diabetes specialist, decreased donor quality, introduction of islet transplantation as a less invasive procedure but probably most of all probably insufficient information on the latest progress and trends achieved in this area. In the area of transplant therapy of diabetes Czech Republic traditionally ranks to the most active countries providing different transplant options according to individual clinical needs including islet transplantation. PMID- 26375706 TI - [Tumours and liver transplants]. AB - Liver transplantation as a curative treatment method can be used for selected primary liver tumours, in particular for hepatocellular carcinoma and rather rare semi-malignant tumours such as epithelioid hemangioendothelioma, further for infiltration of liver by metastatic neuroendocrine tumours (provided that metastases are only located in the liver and the primary tumour was removed) and for benign tumours (hemangiomas and adenomas) with oppression symptoms and size progression. Cholangiocarcinoma is not indicated for liver transplantation at the CKTCH Brno. In recent years liver transplants for hepatocellular carcinoma have increased and hepatocellular carcinoma has also been more frequently found ex post, in the explanted livers. Liver transplantation is indicated in selected patients with a good chance of long-term survival after liver transplantation (a generally accepted limit is 5 year survival of 50 % after transplantation). By 20 March 2015 there were liver transplants carried out on 38 patients - in 25 of them was hepatocellular carcinoma diagnosed before transplantation and in 13 it was found in the liver explants. 5 year survival following transplantation is reached by 53 % of this cohort. 32 % patients suffered from chronic hepatitis C. The longest surviving (32 years) patient at CKTCH Brno had liver transplanted for a big fibrolamellar hepatocellular carcinoma, which points to the prognostic significance of tumour histology: the criterion only considered in some indication schemes for practical reasons. Benign liver tumours (adenomatosis, cystadenoma, hemangioma with oppression symptoms) are rather rare indications and the transplantation results are favourable. 4 patients underwent transplantation for infiltration of liver by carcinoid, tumour recurrence occurred in one. PMID- 26375707 TI - [Solid organ transplantation in the Czech Republic]. AB - Solid organ transplantation (heart, lung, liver, kidney, pancreas, small interesting and their combinations) are standard therapy of terminal organ failure. Czech Republic belongs to the states with developed transplantation program. The results correspond with current knowledge and results of leading centers in the world, as demostrated in this article. Organ donor shortage is major factor limiting development of organ transplantations as elsewhere in the Europe or in the world. PMID- 26375709 TI - Changes in Microbial Plankton Assemblages Induced by Mesoscale Oceanographic Features in the Northern Gulf of Mexico. AB - Mesoscale circulation generated by the Loop Current in the Northern Gulf of Mexico (NGOM) delivers growth-limiting nutrients to the microbial plankton of the euphotic zone. Consequences of physicochemically driven community shifts on higher order consumers and subsequent impacts on the biological carbon pump remain poorly understood. This study evaluates microbial plankton <10 MUm abundance and community structure across both cyclonic and anti-cyclonic circulation features in the NGOM using flow cytometry (SYBR Green I and autofluorescence parameters). Non-parametric multivariate hierarchical cluster analyses indicated that significant spatial variability in community structure exists such that stations that clustered together were defined as having a specific 'microbial signature' (i.e. statistically homogeneous community structure profiles based on relative abundance of microbial groups). Salinity and a combination of sea surface height anomaly and sea surface temperature were determined by distance based linear modeling to be abiotic predictor variables significantly correlated to changes in microbial signatures. Correlations between increased microbial abundance and availability of nitrogen suggest nitrogen limitation of microbial plankton in this open ocean area. Regions of combined coastal water entrainment and mesoscale convergence corresponded to increased heterotrophic prokaryote abundance relative to autotrophic plankton. The results provide an initial assessment of how mesoscale circulation potentially influences microbial plankton abundance and community structure in the NGOM. PMID- 26375708 TI - Laboratory simulations of mate-guarding as a component of the pair-bond in male titi monkeys, Callicebus cupreus. AB - Mate-guarding and territorial aggression (both intra- and inter-sexual) are behavioral components of social monogamy seen in male coppery titi monkeys (Callicebus cupreus) both in the field and in the laboratory. Methodology for studying these behaviors in captivity facilitates the translation of questions between field and laboratory. In this study, we tested whether exposure to a mirror would stimulate mate-guarding behavior in male titi monkeys, and whether this exposure was accompanied by hormonal changes. Eight males were exposed to a mirror condition (treatment) or the back of the mirror (control) for five sessions, and behavioral responses were filmed. Blood samples were taken to measure levels of cortisol, oxytocin, and vasopressin. Lipsmacks (P < 0.0001), arching (P < 0.0001), tail-lashing (P = 0.009), restraining (P = 0.015), and approaches to the female (P = 0.0002) were all higher during the mirror condition, while tail-twining tended to decline during the mirror condition (P = 0.076). Hormones did not vary by experimental treatment, but were correlated with certain behaviors during the presentation of the mirror. While social behaviors changed with mirror exposure, self-directed and mirror-guided behaviors did not, indicating a lack of self-recognition. Use of a mirror was a safe and effective means of investigating mate-guarding behavior in response to a simulated intrusion, with the added benefit of not needing another animal to serve as an intruder; and thus may be of use in providing a laboratory model for natural behavior. Especially, as it eliminates the need for a stimulus animal, it would also be of possible use in investigating responses to a simulated intruder in wild populations of titis and other pithecines. PMID- 26375710 TI - Nanooptics of Plasmonic Nanomatryoshkas: Shrinking the Size of a Core-Shell Junction to Subnanometer. AB - Quantum effects in plasmonic systems play an important role in defining the optical response of structures with subnanometer gaps. Electron tunneling across the gaps can occur, altering both the far-field optical response and the near field confinement and enhancement. In this study, we experimentally and theoretically investigate plasmon coupling in gold "nanomatryoshka" (NM) nanoparticles with different core-shell separations. Plasmon coupling effects between the core and the shell become significant when their separation decreases to 15 nm. When their separation decreases to below 1 nm, the near- and far-field properties can no longer be described by classical approaches but require the inclusion of quantum mechanical effects such as electron transport through the self-assembled monolayer of molecular junction. In addition, surface-enhanced Raman scattering measurements indicate strong electron-transport induced charge transfer across the molecular junction. Our quantum modeling provides an estimate for the AC conductances of molecules in the junction. The insights acquired from this work pave the way for the development of novel quantum plasmonic devices and substrates for surface-enhanced Raman scattering. PMID- 26375711 TI - Population Genetic Diversity in the Australian 'Seascape': A Bioregion Approach. AB - Genetic diversity within species may promote resilience to environmental change, yet little is known about how such variation is distributed at broad geographic scales. Here we develop a novel Bayesian methodology to analyse multi-species genetic diversity data in order to identify regions of high or low genetic diversity. We apply this method to co-distributed taxa from Australian marine waters. We extracted published summary statistics of population genetic diversity from 118 studies of 101 species and > 1000 populations from the Australian marine economic zone. We analysed these data using two approaches: a linear mixed model for standardised data, and a mixed beta-regression for unstandardised data, within a Bayesian framework. Our beta-regression approach performed better than models using standardised data, based on posterior predictive tests. The best model included region (Integrated Marine and Coastal Regionalisation of Australia (IMCRA) bioregions), latitude and latitude squared. Removing region as an explanatory variable greatly reduced model performance (delta DIC 23.4). Several bioregions were identified as possessing notably high genetic diversity. Genetic diversity increased towards the equator with a 'hump' in diversity across the range studied (-9.4 to -43.7 degrees S). Our results suggest that factors correlated with both region and latitude play a role in shaping intra-specific genetic diversity, and that bioregion can be a useful management unit for intra specific as well as species biodiversity. Our novel statistical model should prove useful for future analyses of within species genetic diversity at broad taxonomic and geographic scales. PMID- 26375712 TI - Legionella Infection in Pregnancy: The Forgotten Pathogen in Septic Shock. AB - BACKGROUND: Of eight cases of Legionella infection in pregnancy reported over 35 years, there was one case of maternal septic shock with poor outcome, one recovery with good outcome, and six with poor outcome. CASE: A 30-year-old woman, gravida 2 para 1, at 28 weeks of gestation presented with a high fever, cough, nausea, and vomiting. She deteriorated despite treatment for presumed urosepsis, was transferred to the intensive care unit, and remained intubated for 10 days receiving cardiovascular support, antivirals, antifungals, and multiple wide spectrum antibiotics. Legionella infection antigen testing was performed on hospital day 1 and returned as positive. Azithromycin, started before the testing results became available, was continued for 14 days. The patient recovered, and the pregnancy progressed uneventfully to term. CONCLUSION: Legionella infection should be considered with maternal deterioration despite broad-spectrum antibiotic coverage. A favorable outcome is possible with early diagnosis and treatment. PMID- 26375713 TI - Use of an Obstetric Balloon for Postabortion Hemorrhage With Disseminated Intravascular Coagulation. AB - BACKGROUND: Postabortion hemorrhage occurs in up to 2% of second-trimester pregnancy terminations. Postabortion hemorrhage is the leading cause of postabortion maternal mortality. We report the successful use of an obstetric balloon for second-trimester postabortion hemorrhage complicated by disseminated intravascular coagulation. CASE: A 38-year-old multigravid woman presented with hypovolemic shock from disseminated intravascular coagulation after second trimester termination of an anomalous fetus. An intrauterine Foley catheter filled with 60 mL of fluid failed to tamponade bleeding. An obstetric balloon filled with 330 mL of fluid temporized bleeding until the patient's coagulopathy was corrected. CONCLUSION: An obstetric balloon should be considered in the management of second-trimester postabortion hemorrhage complicated by disseminated intravascular coagulation while coagulopathy is corrected. PMID- 26375714 TI - Postmenopausal Invasive Endometriosis Requiring Supralevator Pelvic Exenteration. AB - BACKGROUND: Endometriosis is rare in postmenopausal women. We report a case of invasive pelvic endometriosis in a postmenopausal woman requiring a supralevator pelvic exenteration for palliation of symptoms and for tissue diagnosis. CASE: A 65-year-old woman with a history of total abdominal hysterectomy and bilateral salpingo-oophorectomy for endometriosis at age 43 years presented with acute vaginal bleeding, hematuria, and a recently diagnosed pelvic mass. Biopsies revealed endometriosis, and she underwent supralevator pelvic exenteration with vaginectomy, end colostomy, ileal conduit, and coagulation of endometriotic implants. Pathologic examination showed invasive endometriosis and no evidence of malignancy. CONCLUSION: Endometriosis should remain on the differential diagnosis for pelvic mass in a postmenopausal woman, although suspicion for malignancy should remain high. PMID- 26375715 TI - A Pregnant Patient With Ebola Virus Disease. AB - BACKGROUND: Limited data suggest Ebola virus disease during pregnancy is associated with high maternal and fetal mortality. CASE: A 34-year-old woman, gravida 4 para 3, at 36 weeks of gestation was admitted to an Ebola treatment unit in Sierra Leone with Ebola virus disease confirmed by laboratory testing of maternal blood for Ebola RNA. She complained of headache, cough, and arthralgia for 7 days but was afebrile. Eleven days later, intrauterine fetal death was diagnosed; the following day, maternal blood was negative for Ebola viral RNA. Labor was induced and resulted in the vaginal delivery of a stillborn fetus. The mother recovered. Her vaginal secretions (on the day of induction), a placenta fragment, umbilical cord, and neonatal buccal swabs were positive for Ebola RNA. No exposed health care workers were infected. CONCLUSION: This case illustrates that pregnant women can survive infection with Ebola virus disease and be cared for and delivered without infection of their health care workers. PMID- 26375716 TI - Fetal-Maternal Hemorrhage Detected by Sudden Disappearance of Rh Immune Globulin Related Anti-D. AB - BACKGROUND: Fetal-maternal hemorrhage is usually spontaneous and goes undetected but can be associated with adverse perinatal outcomes. CASE: We describe the detection of a fetal-maternal hemorrhage by abrupt disappearance of prophylactic anti-D on antibody screen in an Rh-negative mother with dichorionic twins admitted for atrial flutter of one twin. Both rosette and Kleihauer-Betke tests were positive. The diagnosis was confirmed by anemia in one twin at birth. CONCLUSION: Fetal-maternal hemorrhage requires a high index of suspicion for diagnosis. An unexpected sudden decline in Rh immune globulin-related anti-D may be an indication of fetal-maternal hemorrhage. PMID- 26375717 TI - Alcoholic Pancreatitis Masquerading as Preeclampsia. AB - BACKGROUND: Coexisting medical complications in pregnancy can present in a fashion similar to preeclampsia and can be challenging to differentiate. CASE: We present a patient who, at 27 3/7 weeks of gestation, fulfilled diagnostic criteria for severe preeclampsia, including hypertension, proteinuria, headache, abnormal serum creatinine levels, thrombocytopenia, and liver function abnormalities, but who nevertheless did not have preeclampsia. Instead, she was diagnosed with alcoholic pancreatitis based on a history of heavy alcohol use and elevated amylase and lipase. Abnormal laboratory values resolved with supportive therapy, and she continued to term without subsequent recurrence of proteinuria or hypertension. CONCLUSION: Alcoholic pancreatitis can be mistaken for preeclampsia. PMID- 26375718 TI - From Multisite Polymerization Catalysis to Sustainable Materials and All Polyolefin Composites. PMID- 26375719 TI - Dimethadione embryotoxicity in the rat is neither correlated with maternal systemic drug concentrations nor embryonic tissue levels. AB - Pregnant rats treated with dimethadione (DMO), the N-demethylated metabolite of the anticonvulsant trimethadione, produce offspring having a 74% incidence of congenital heart defects (CHD); however, the incidence of CHD has high inter litter variability (40-100%) that presents a challenge when studying the initiating events prior to the presentation of an abnormal phenotype. We hypothesized that the variability in CHD incidence was the result of differences in maternal systemic concentrations or embryonic tissue concentrations of DMO. To test this hypothesis, dams were administered 300 mg/kg DMO every 12h from the evening of gestational day (GD) 8 until the morning of GD 11 (six total doses). Maternal serum levels of DMO were assessed on GD 11, 12, 13, 14, 15, 18 and 21. Embryonic tissue concentrations of DMO were assessed on GD 11, 12, 13 and 14. In a separate cohort of GD 12 embryos, DMO concentrations and parameters of growth and development were assessed to determine if tissue levels of DMO were correlated with these endpoints. Embryos were exposed directly to different concentrations of DMO with whole embryo culture (WEC) and their growth and development assessed. Key findings were that neither maternal systemic concentrations nor tissue concentrations of DMO identified embryos that were sensitive or resistant to DMO in vivo. Direct exposure of embryos to DMO via WEC also failed to show correlations between embryonic concentrations of DMO with developmental outcomes in vitro. We conclude that neither maternal serum nor embryonic tissue concentrations of DMO predict embryonic outcome. PMID- 26375720 TI - Spatio-Temporal Variations in Stream-Aquifer Interactions Following Construction of Weirs in Korea. AB - The "Four Major Rivers Restoration Project" was conducted to secure sufficient water resources, introduce comprehensive flood control measures, improve water quality, and restore river ecosystems in Korea. As a part of the project, 16 sites were dredged and weirs were installed in the Han, Geum, Yeongsan, and Nakdong Rivers from late 2010 to early 2012. Groundwater data were obtained from 213 groundwater monitoring wells near the four major rivers to analyze the impacts of weir construction on the nearby groundwater flow system. The groundwater level and chemical characteristics were analyzed to investigate how the groundwater flow system and water quality changed following weir construction. Our results show that the groundwater level immediately increased with increased river levels following weir construction. In addition, the hydrologic condition of some rivers upstream of the weirs was changed from gaining to losing streams. Consequently, the direction of groundwater flow changed from perpendicular to parallel to the river, and groundwater downstream of the weir became recharged from the area upstream of the weir. This should affect groundwater quality, which should become similar to the river water; however, this change has not yet been observed. Therefore, both further monitoring of the groundwater quality and further hydrogeochemical analysis are required for quantitative evaluation of the effects of weir construction in the study area. PMID- 26375721 TI - Correction to Photodegradation of Imidacloprid in Aqueous Solution by the Metal Free Catalyst Graphitic Carbon Nitride using an Energy-Saving Lamp. PMID- 26375722 TI - Clinical Research Abstracts of the British Equine Veterinary Association Congress 2015. AB - REASONS FOR PERFORMING STUDY: Training and rehabilitation techniques which improve core muscle strength are beneficial for improvement of dynamic stability of the equine vertebral column. The EquibandTM system, consisting of resistance bands attached to a customised saddle pad, is suggested to provide constant proprioceptive feedback during motion to encourage recruitment of abdominal and hindquarter musculature. OBJECTIVES: To quantify the effect of the EquibandTM system on back kinematics and movement symmetry. STUDY DESIGN: Longitudinal intervention study. METHODS: Quantitative analysis of back movement and gait symmetry before/after a 4-week exercise programme. Inertial sensor data was collected from 7 horses at Weeks 0 and 4 of a fixed exercise protocol. Analysis with and without the EquibandTM system was completed at trot in hand on a hard surface, and for both reins on the lunge on a soft surface. Six back kinematic and 3 movement symmetry parameters were calculated according to published methods. Movement symmetry values were side-corrected to allow comparison between reins on the lunge. A mixed model (P<0.05) evaluated the effects of the EquibandTM system over time, and trotting direction on back kinematic and movement symmetry parameters. RESULTS: The EquibandTM system significantly reduced (all P<0.02) roll, pitch and mediolateral displacement in the cranial-mid thoracic region. Across all horses, back displacement and range of motion values were significantly greater (P<0.01) on the lunge than in a straight line, movement symmetry was consistent with having corrected all horses to be left sided. CONCLUSION: Preliminary results suggest the EquibandTM system may aid dynamic stabilisation of the vertebral column. Ethical animal research: This study was authorised by the Ethics and Welfare Committee of the Royal Veterinary College, London (URN Approval Number 1238). Written consent was obtained from the owner/keeper of each animal. SOURCE OF FUNDING: Royal Veterinary College. Competing interests: N.C. Stubbs and N. Rombach developed the EquibandTM system. The remaining authors have no competing interests. PMID- 26375723 TI - Assessment of Botulinum Toxin Aesthetic Outcomes: Clinical Study vs Real-World Practice. PMID- 26375724 TI - A Prospective, Observational Pilot Study of the Use of Urinary Antimicrobial Peptides in Diagnosing Emergency Department Patients With Positive Urine Cultures. AB - OBJECTIVES: Urinary tract infection (UTI) often represents a diagnostic challenge in the emergency department (ED) where urine culture results are generally not available and other tests demonstrate limited sensitivity and specificity. Antimicrobial peptides (AMPs) are components of the innate immune system that have demonstrated increased urinary levels in response to infection both in children and in adults with chronic UTI. The objective of this study was to determine the relationship between urinary AMP levels and positive urine cultures in adult ED patients with suspected UTI. METHODS: This was a prospective, observational study of adult ED patients with suspected UTI. Enzyme-linked immunosorbent assays were performed to measure urine levels of AMPs: human neutrophil peptides 1-3 (HNP1-3), human alpha-defensin 5 (HD5), human beta defensin 2 (hBD-2), and cathelicidin (LL-37). Comparisons between positive and negative cultures were performed using Wilcoxon rank sum tests and receiver operating characteristic curves, with calculation of area under the curve (AUC). Data were also analyzed for the older adult subgroup. RESULTS: Of 40 patients enrolled, 23 (58%) were >= 65 years, 25 were female (64%), and seven (17%) were nonwhite. Cultures were positive in 13 (32%), including seven in those >= 65 years old. HNP1-3, HD5, and hBD-2 levels were significantly higher in those with positive than negative urine cultures. Median HNP1-3 was 5.39 ng/mg (interquartile range [IQR] = 2.74 to 11.09) in positive vs. 0.81 ng/mg (IQR = 0.06 to 3.87) in negative cultures. Median HD5 was 4.75 pg/mg (IQR = 1.6 to 22.7) in positive versus 0.00 pg/mg (IQR = 0 to 2.60) in negative cultures, and median hBD-2 was 0.13 pg/mg (IQR = 0.08 to 0.17) in positive versus 0.02 pg/mg (IQR = 0 to 0.04) in negative cultures (p < 0.05 for all). Findings were similar for adults >= 65 years. The AUC was >= 0.75 for all three AMPs, both overall and in the older adult subgroup. LL-37 was not significantly higher in patients with positive urine culture. However, LL-37 expression is vitamin D dependent, and inadequate serum levels (< 30 ng/mL) were present in 72% of those tested. CONCLUSIONS: Urinary levels of HNP1-3, HD5, and hBD-2 are significantly greater in the presence of positive urine cultures in ED patients with suspected UTI. These findings are maintained in the high-risk subgroup of older adults. PMID- 26375725 TI - Quaternary Indolizidine and Indolizidone Iminosugars as Potential Immunostimulating and Glycosidase Inhibitory Agents: Synthesis, Conformational Analysis, Biological Activity, and Molecular Docking Study. AB - New quaternary indolizidine iminosugars, with hydroxymethyl group at the ring junction, namely, C-8a-hydroxymethyl-1-deoxycastanospermine congeners 1a, 2a, 3a and their 3-oxo analogs 1b, 2b, and 3b were synthesized by using intramolecular reductive aminocyclization/lactamization of d-mannose/D-glucose derived C5-gamma azido esters as a key step wherein both the rings of the indolizidine skeleton were built up in one pot following the cascade reaction pathway. The conformations ((5)C8 or (8)C5) of 1-3 were assigned on the basis of the (1)H NMR studies. All compounds were found to be potent inhibitors of various glycosidase enzymes with Ki and IC50 values in the micromolar/nanomolar concentration range and further substantiated by molecular docking studies. The effect of synthesized iminosugars 1-3 on the cytokine secretion of IL-4, IL-6, and IFN-gamma was evaluated. All compounds were found to be TH1 bias increasing the TH1/TH2 cytokines ratio (IL-6 and IL-4) indicating their potency as immunostimulating agents. Our study suggests that immunomodulatory activity of indolizidine iminosugars can be tuned by minor structural/stereochemical alterations. PMID- 26375726 TI - Virtual Touch quantification using acoustic radiation force impulse (ARFI) technology for the evaluation of focal solid renal lesions: preliminary findings. AB - AIM: To evaluate potential value of Virtual Touch quantification (VTQ) of acoustic radiation force impulse (ARFI) imaging for characterising focal solid renal lesions. MATERIALS AND METHODS: Two independent operators performed 10 and five measurements of each lesion and adjacent renal cortex, respectively. Mean shear wave velocity (SWV) and shear wave velocity ratio (SWR) of histotypes were compared. RESULTS: One hundred and ninety-seven renal lesions were evaluated, including 155 renal cell carcinomas (RCCs; 129 clear-cell RCCs [ccRCCs], 14 papillary RCCs [pRCCs], and 12 chromophobe RCCs [cRCCs]) and 42 angiomyolipomas (AMLs). The interoperator reproducibility of SWV of renal tumours and renal cortex were good (ICC=0.852, and 0.903, respectively). SWV of the renal cortex at a depth of <4 cm was significant higher than that at a depth of >4 cm. Regardless of the subtypes of RCC, SWV and SWR of RCCs differed significantly from those of AMLs (2.28+/-0.85 versus 1.98+/-0.85; 1.09+/-0.56 versus 0.78+/-0.34; p=0.045 and p<0.001, respectively). At cut-off points of SWV >1.87 m/s or SWR >0.84 to differentiate RCCs from AMLs, the sensitivity and specificity were 47.5%, 33.2% or 47.5%, 30.2%, respectively. When the subtypes of RCCs were taken into account, SWV and SWR of ccRCCs were significantly higher than those of pRCCs, cRCCs, and AMLs, while there was no significant difference among the latter. With SWV >1.98 m/s or SWR >0.80 as the cut-off point to differentiate ccRCCs from other renal tumours, the sensitivity and specificity were 69.8%, 65% or 76.8%, 73.4%, respectively. CONCLUSION: The ARFI technique offers additional information regarding renal tumour elasticity with good reproducibility. SWV and SWR are potential biomarkers in this setting, helping to differentiate ccRCC from other renal tumour histotypes. PMID- 26375727 TI - A case of an epithelioid glioblastoma with the BRAF V600E mutation colocalized with BRAF intact low-grade diffuse astrocytoma. AB - Epithelioid glioblastomas are one of the rarest histological variants of glioblastomas, which are not formally recognized by the World Health Organization (WHO) classification. Epithelioid glioblastomas usually occur as primary lesions, but there have been several reports of secondary epithelioid glioblastomas or epithelioid glioblastomas with pre- or co-existing lesions to date. The serine/threonine-protein kinase B-Raf (BRAF) V600E mutation has been found at a high frequency of 54% in epithelioid glioblastomas. We present a case of a 26 year-old female patient with an epithelioid glioblastoma with the BRAF V600E mutation in her right frontal lobe. In the present case, a low-grade diffuse astrocytoma component had colocalized with the epithelioid glioblastoma. The component presented prominent calcification on neuroimages as well as by histology, and low-grade diffuse astrocytoma was considered to be a precursor lesion of an epithelioid glioblastoma. However, the BRAF V600E mutation was detected only in epithelioid glioblastoma but not in low-grade diffuse astrocytoma. To the best of our knowledge, this is the first report demonstrating a discrepancy in the BRAF V600E mutation states between epithelioid glioblastoma and colocalized low-grade astrocytoma. PMID- 26375728 TI - The value of histopathological examination of salivary gland biopsies in diagnosis, prognosis and treatment of Sjogren's Syndrome. AB - Primary Sjogren's syndrome (pSS) is a complex autoimmune disease characterised by local exocrine glandular involvement and systemic multiorgan manifestations. In this review we will discuss the value of the histological examination of the salivary glands in the classification criteria, and more recently as prognostic tool for patient stratification and monitoring. The limitations of the current tools used to assess salivary gland pathology in pSS will also be reviewed in relation to using salivary gland biopsy analysis as an outcome measure in clinical trials. PMID- 26375729 TI - Clinical Research Abstracts of the British Equine Veterinary Association Congress 2015. AB - REASONS FOR PERFORMING STUDY: Although fasciolosis is an important livestock disease worldwide, the public health importance of human fasciolosis has increased in recent years and it is recognised as an important re-emerging zoonotic disease, its epidemiology and pathogenicity in donkeys, and the epidemiological role they may play have not been determined. OBJECTIVES: To investigate the epidemiology and pathogenicity of fasciolosis in donkeys. STUDY DESIGN: Cross-sectional coprological and retrospective post-mortem study. METHODS: Faecal samples collected from 803 randomly selected working donkeys from the central region of Ethiopia were analysed by a sedimentation-centrifugation flotation technique. Further data on liver-flukes and associated pathologies were obtained by routine post mortem examinations of 112 donkeys, subjected to euthanasia on welfare grounds or died. Data were analysed using a generalised linear model and multivariate binary logistic regression in R statistical package with significance level of statistical tests set at P<0.05. RESULTS: Infection prevalences of 44.4% and 41.9% were obtained in coprologically and post mortem examined donkeys, respectively, irrespective of their age. Both Fasciola hepatica and Fasciola gigantica were identified with the mean infection intensity of 30 flukes. Older donkeys (>=8 years) were found harbouring a significantly higher worm burden (P<0.0001). Gross and histopathologies of hyperplasia and thickening of the bile ducts, fibrosis of large portal areas and irregular bile duct proliferation and hypertrophy were noted. CONCLUSIONS: The high infection prevalence of fasciolosis and the associated hepatic pathologies in working donkeys shows not only the susceptibility of donkeys and the impact it has on their health, but also indicates the important role they can play in the epidemiology of both livestock and human fasciolosis. These further demonstrate the need for these animals to be considered in the overall epidemiological studies and for sound control strategies and prevention of fasciolosis. Ethical animal research: The research underwent ethical review and the use of animals was approved by the Directors of The Donkey Sanctuary. Consent of the owners was obtained to use their animals. SOURCE OF FUNDING: The Donkey Sanctuary. Competing interests: None declared. PMID- 26375730 TI - Evolutionary characterization of the emerging porcine epidemic diarrhea virus worldwide and 2014 epidemic in Taiwan. AB - Since 2010, a new variant of PEDV belonging to Genogroup 2 has been transmitting in China and further spreading to the Unites States and other Asian countries including Taiwan. In order to characterize in detail the temporal and geographic relationships among PEDV strains, the present study systematically evaluated the evolutionary patterns and phylogenetic resolution in each gene of the whole PEDV genome in order to determine which regions provided the maximal interpretative power. The result was further applied to identify the origin of PEDV that caused the 2014 epidemic in Taiwan. Thirty-four full genome sequences were downloaded from GenBank and divided into three non-mutually exclusive groups, namely, worldwide, Genogroup 2 and China, to cover different ranges of secular and spatial trends. Each dataset was then divided into different alignments by different genes for likelihood mapping and phylogenetic analysis. Our study suggested that both nsp3 and S genes contained the highest phylogenetic signal with substitution rate and phylogenetic topology similar to those obtained from the complete genome. Furthermore, the proportion of nodes with high posterior support (posterior probability >0.8) was similar between nsp3 and S genes. The nsp3 gene sequences from three clinical samples of swine with PEDV infections were aligned with other strains available from GenBank and the results suggested that the virus responsible for the 2014 PEDV outbreak in Taiwan clustered together with Clade I from the US within Genogroup 2. In conclusion, the current study identified the nsp3 gene as an alternative marker for a rapid and unequivocal classification of the circulating PEDV strains which provides complementary information to the S gene in identifying the emergence of epidemic strain resulting from recombination. PMID- 26375731 TI - Genome characterisation of two Ljungan virus isolates from wild bank voles (Myodes glareolus) in Sweden. AB - Ljungan virus (LV) (family Picornaviridae, genus Parechovirus) is a suspected zoonotic pathogen with associations to human disease in Sweden. LV is a single stranded RNA virus with a positive sense genome. There are five published Ljungan virus strains, three isolated from Sweden and two from America, and are classified into four genotypes. A further two strains described here were isolated from wild bank voles (Myodes glareolus) caught in Vastmanlands county, Sweden in 1994. These strains were sequenced using next generation pyrosequencing technology on the GS454flx platform. Genetic and phylogenetic analysis of the obtained genomes confirms isolates LV340 and LV342 as two new putative members of genotype 2 along with LV145SL, with 92% and 99% nucleotide identities respectively. Only two codon sites throughout the entire genome were identified as undergoing positive selection, both situated within the VP3 structural region, in or near to major antigenic sites. Whilst these two strains do not constitute new genotypes they provide evidence, though weakly supported, which suggests the evolution of Ljungan viruses to be relatively slow, a characteristic unlike other picornaviruses. Additional genomic sequences are urgently required for Ljungan virus strains, particularly from different locations or hosts, to fully understand the evolutionary and epidemiological properties of this potentially zoonotic virus. PMID- 26375732 TI - Tensile Bond Strength between Soft Liners and Two Chemically Different Denture Base Materials: Effect of Thermocycling. AB - PURPOSE: The bond strength of soft denture liner to a recently introduced denture base resin after thermocycling has not been compared to traditional denture base materials. The objective of this study was to investigate the effects of thermocycling on the tensile bond strength of soft denture liners to two chemically different denture base resins, polymethyl methacrylate (PMMA) and urethane dimethacrylate (UDMA). MATERIALS AND METHODS: A total of 48 PMMA and UDMA tensile test specimens were fabricated by attaching two different soft denture liners (Molloplast-B, Permaflex) according to the manufacturers' instructions and assigned to two groups. Half of the specimens for each group were stored in water for 1 week, and the other half were thermocycled (5000 cycles) between baths of 5 degrees C and 55 degrees C. Specimens were mounted on a universal testing machine with a 5 mm/min crosshead speed. The data were analyzed with three-way ANOVA and post hoc Tukey-Kramer multiple comparisons tests (alpha = 0.05). RESULTS: The highest bond strength was measured in the specimens from the UDMA/Molloplast groups, and the lowest was seen in the PMMA/Permaflex group. No significant difference in bond strength was detected in PMMA/Permaflex groups after thermocycling (p = 0.082), whereas other groups exhibited significant differences after thermocycling (p < 0.05). CONCLUSIONS: Thermocycling decreased the bond strength values in both the PMMA and UDMA groups. Regardless of types of soft liners, PMMA specimens presented lower bond strength values than UDMA specimens, both before and after thermocycling. PMID- 26375733 TI - Charging Dynamics of Aerosol OT Inverse Micelles. AB - Aerosol OT (AOT) is a commonly used surfactant and charging agent in nonpolar liquids. Properties such as the conductivity of AOT suspensions in nonpolar liquids and the behavior of charged AOT inverse micelles at interfaces have been studied recently, but still little is known about the generation dynamics of charged AOT inverse micelles. In this article, the generation dynamics of charged AOT inverse micelles in dodecane are investigated with transient current measurements. At low applied voltages, the generation rate is sufficiently fast to maintain the equilibrium concentration of charged inverse micelles, such that the current scales proportionally with the applied voltage. However, above a threshold voltage the current becomes limited by the generation of charged inverse micelles. Al2O3-coated electrodes are used to achieve these high-voltage current measurements while reducing surface generation currents. The dependency of the resulting generation-limited currents with the micelle concentration and the liquid volume is compatible with a bulk disproportionation mechanism. The measured currents are analyzed using a model based on drift, generation, and recombination of charged inverse micelles and the corresponding generation and recombination rates of charged AOT inverse micelles have been determined. PMID- 26375734 TI - Gastrointestinal Behavior of Weakly Acidic BCS Class II Drugs in Man--Case Study of Diclofenac Potassium. AB - This study aimed to investigate the gastrointestinal supersaturation and precipitation behavior of a weakly acidic Biopharmaceutics Classification System (BCS) Class II drug in healthy volunteers. For this purpose, a tablet containing 50 mg diclofenac potassium (Cataflam((r))) was predissolved in 240 mL of water and this solution was subsequently orally administered to five healthy volunteers under fasted and fed state conditions with or without concomitant use of a proton pump inhibitor (PPI) (40 mg esomeprazole, Nexiam((r))). Subsequently, total diclofenac content and dissolved intraluminal drug concentrations as well as drug thermodynamic solubility were determined in gastrointestinal aspirates. In all volunteers, gastric supersaturation resulted in precipitation of diclofenac in the stomach. The extent of precipitation correlated well with gastric pH (r = - 0.78). pH dependency of precipitation was corroborated by the absence of precipitate in the stomach after coadministration of a meal and/or a PPI. Diclofenac was found to be fully dissolved in the duodenum in all test conditions. It can be concluded that substantial pH-dependent gastric precipitation of a weakly acidic BCS Class II drug administered as a solution occurs in humans. With regard to its implications for intestinal absorption, results suggest the instantaneous redissolution of gastric drug precipitate upon transfer to the duodenum. PMID- 26375735 TI - [Diagnosis and management of cow's protein milk allergy in infant]. AB - BACKGROUND: Cow's milk protein allergy (CMPA) can be responsible of a variety of symptoms and can be caused by IgE or non-IgEmediated reactions. The remaining questions concern the diagnosis (what are the most suggestive clinical manifestations, the laboratory evaluations which play a supporting role, and the management of CMPA in breast fed infants and formula-fed infants. METHODS: Review of the pub med, science direct, Cochrane library, using the key words cow's milk protein allergy, guideline, and child. Evidence was levelled A, B, C. RESULTS: No symptom is pathognomonic. A thorough history and careful clinical examination are necessary to suspect the disease. Skin prick tests, and serum specific IgE are only indicative of sensitivation to CMP. A double-blind placebo-controlled challenge is considered the gold standard in diagnosis, but in practice only an open challenge is performed. The patient with suspected pathology will follow a cow's milk free diet for 2-4 weeks. Formula-fed infants get an extensively hydrolyzed formula .If the allergy is present, clinical manifestations will disappear. If symptoms do not improve, an amino acid based formula should be considered. In severe Cow's milk protein allergy with life-threatening symptoms, an amino-acid formula is recommended. The infant should be maintained on an elimination diet until the infant is between 9-12 months or at least for 6 months. The overall natural evolution of the disease is favorable with most patients achieving tolerance to milk by the age of five years. CONCLUSION: The importance of defined diagnostic criteria needs to be emphasized. It precludes infants from an unnecessary diet and avoids delay in diagnosis, which can lead to malnutrition. PMID- 26375736 TI - [Efficacy of misoprostol for medical termination of pregnancy in second trimester : Prospective study]. AB - AIM: To investigate the efficacy of misoprostol used alone, and the time of fetal expulsion for medical termination of pregnancy in the second trimester. PATIENTS AND METHODS: 50 patients were enrolled in a prospective study over two years and in whom termination of pregnancy was indicated between 14 and 28 weeks of amenorrhea. Misoprostol was reported in a well-defined protocol: group 1: 2 tablets every 3 hours as intra vaginal, group 2: half dose for women bull 4th or more or carrying a scarred uterus for terms greater than or equal to 22 weeks of amenorrhea. RESULTS: 48 patients expelled misoprostol alone and we have used an aspiration in two cases. The period of expulsion for 24 hours was 97% for the first group and 90% for the second. CONCLUSION: using misoprostol within this protocol is effective and reduce the time required for the fetal expulsion of the second trimester pregnancy. PMID- 26375737 TI - [Chemotherapy-induced febrile neutropenia: About 186 episodes. Clinical, microbiological and therapeutic characteristics]. AB - BACKGROUND: One of the major side effects of anti-proliferative treatment is their medullar toxicity. This toxicity is particularly important in neutrophils and leads to a neutropenia. Fever during these episodes of neutropenia is a frequent complication but remains of indeterminate origin in 60% of cases. It's a medical emergency because of rapid evolution and a significant increase in mortality up to 10%. Thus, these episodes should be prevented and treated in priority with un empiric and large spectrum antibiotherapy, taking into account the bacterial ecology of each hospital. AIM: The aim of this study was to determinate the clinical, therapeutic and evolutive characteristics of febrile neutropenia (FN). METHODS: This retrospective study concerned 186 episodes of FN in 136 patients treated for solid tumors and lymphoma in the department of medical oncology of Sfax from january 2006 to December 2010. RESULTS: Mean age was 40 years (1 to 81) and sex ratio at 0.97. They were trated mainly solid tumors in 86.02%. Median time to onset of FN was 11 days and the mean duration of neutropenia was 5 days. 24.2% had a neutrophil count (ANC) <100 / mm3. Fever was clinically documented in 33.87%. Patients have mainly ORL clinical manifestations (38.46%) and specially mucositis (50%). Only 17.2% of cases were microbiologically documented and a bacteria was isolated in 76.46% of them in blood cultures, Gram-negative bacilli (GNB) accounted for the majority of organisms isolated in different samples in 66.66% of cases. Enterobacteriaceae were the most frequent dominated by Klebsiella spp, followed by Escherichia coli. Pseudomonas aeruginosa ranked second after the Enterobacteriaceae (21.21%). The Gram-positive cocci (GPC) were found in 24.24% mainly Staphylococcus aureus. The first line of empirical antibiotic therapy was associated in 88.7% of ceftazidime and amikacin or a fluoroquinolone that has to have an efficiency of 72.12%. The rate of death due to infection in our series was 9.14%. CONCLUSION: Our results are consistent with data in the literature concerning the short duration of neutropenia, causing fever and mortality, but our bacterial epidemiology is different from the current literature, where there is a predominance of CGP unlike our predominantly the BGN. And prescribing empiric antibiotic therapy must take into account the epidemiological and ecological particularities of each country, each hospital or each department. PMID- 26375738 TI - [Nocturnal gastroesophageal reflux. About a pH metric series]. AB - BACKGROUND: Nocturnal gastroesophageal reflux has been shown to be associated with the more severe forms of gastroesophageal reflux disease (GERD), particularly with extraesophageal manifestations as well as complications of mucosal damage. AIM: To determine the frequency of nocturnal gastro esophageal reflux disease on 24-hour esophageal pH monitoring in patients with digestives or extra-digestives symptoms and to evaluate the clinical and pHmetric characteristics of nocturnal reflux in these patients. METHODS: We conducted a retrospective study based on results of 24- hour esophageal pH monitoring during a 11-year period in patients with or without digestive symptoms of gastroesophageal reflux disease. The nocturnal gastroesophgeal reflux was defined. RESULTS: We studied 696 patients (299 men, 397 women; mean age: 34.05 years). Gastroesophageal reflux was found in 350 patients (50%). Nocturnal reflux was observed in 240 patients (34.3%), mostly in association with pathological reflux in the total period (223 cases). Compared to the diurnal period, the nocturnal period was characterized by fewer number of reflux episodes (21.9+/ 27.4 vs 67.4+/-5.,1 ; p<0.0001), more longer duration of reflux episodes (24.4+/ 37.9 minutes vs 13.9+/- 17.5 minutes ; p<0.001), and a lower symptomatic correlation (26% vs 45% ; p=0.0005). CONCLUSION: Nocturnal reflux is associated with overall reflux on the 24 hour examination. Nocturnal period is characterized by longer reflux episodes, less number of reflux episodes and less symptomatic correlation. PMID- 26375739 TI - Perioperative chemotherapy in locally advanced gastric cancer. A retrospective study about 25 cases. AB - BACKGROUND: Perioperative chemotherapy containing 5FU, Cisplatin +/- Docetaxel is one of the most active regimens in advanced gastric cancer. OBJECTIVE: To report epidemiological and clinical profile and therapeutic results of perioperative chemotherapy in locally advanced gastric cancer in Tunisia. METHODS: Our retrospective study concerned patients with histologically confirmed advanced gastric cancer treated at the institute Salah Azaiez of Tunis. They received 2-3 cycles / 3 weeks of neoadjuvant chemotherapy based on FP (5FU and Cisplatin) or TPF (Docetaxel-Cisplatin-5FU). RESULTS: From 2010 to 2012, 25 patients with a median age of 60 years and 7.3 sex-ratio received neoadjuvant chemotherapy. Protocols used were TFP in 20 and FP in 5 patients, 17 patients receiving more than 2 cycles. Side effects were represented by mucositis grade 3 in 2 patients, neutropenia grade 3/4 in 3 patients and renal failure in 5 patients. After neoadjuvant chemotherapy, we observed 40% of partial response and 20% of stable disease. Six patients (24%) underwent surgery, curative in 4 (R0 in 3 cases) by total gastrectomy and D2 lymphadenectomy and palliative in 2 cases due to peritoneal carcinomatosis. With a median follow up of 16 months, median overall survival was 16 months (2-21 months). CONCLUSION: Probably due to the very bulky and advanced stages of our gastric cancer cases, neoadjuvant chemotherapy using FP+/-T showed no benefit in the treatment of locally advanced gastric cancer in Tunisian patients. PMID- 26375740 TI - [Nicotine dependance and carbon monoxide intoxication among adult smokers]. AB - BACKGROUND: The high nicotine dependence is one of the contributing factors to failure of attempts to quit. Moreover, the carbon monoxide (CO) intoxication, proportional to the intensity of smoking, is the basis of cardiovascular complications. OBJECTIVES: To describe tobacco consumption and the degree of CO intoxication, as well as to assess nicotine dependence and identify its determinants in a population of adult smokers. METHODS: This is a descriptive cross-sectional study, based on a selfadministered questionnaire and a dosage of CO in expired air among smokers who participated in awareness sessions conducted in public places and academic institutions in the city of Monastir. Multivariate analysis was based on a binary logistic regression. RESULTS: A total of 914 smokers participated in our survey whose mean age was 29.5 +/- 12.4 years. More than 2/3 of cases (68.7 %) were strongly addicted to nicotine. Heavy smokers (consumption > 20 cigarettes / day) accounted for 28 % of subjects aged under 30 and 59% of older adults (p < 10-4). Determinants of strong tobacco dependence were age of first cigarette ( OR = 0.912 ) , duration of tobacco consumption (OR = 1.059 ) , alcohol consumption (OR = 1.764 ) , sedentarity (OR = 2.024 ) and the rate expired CO (OR = 1.059 ) . The mean rate of exhaled CO was 13.1 +/- 11.1 ppm. It was positively correlated with Fagerstrom score (r = 0.5, p < 10-4) and the number of cigarettes smoked before dosing CO (r = 0.6, p < 10-4). In the contrary, it was negatively correlated to the time elapsed between the last cigarette and the test (r = - 0.2, p = 0.001). CONCLUSION: The results of this study focused on smoking addiction and its determinants. They encourage us to strengthen efforts for effective implementation of the WHO Framework Convention of Tobacco control in Tunisia. PMID- 26375741 TI - Gilbert syndrome acts as a risk factor of developing gallstone among beta hemoglobinopathy Tunisian patients. AB - BACKGROUND: As a result of chronic hemolysis, hyperbilirubinemia is often observed, leading to the formation of pigment cholelithiasis which could be busted by the presence of uridine diphosphoglucuronosyltransferase 1A1 defects. AIM: Herein, we investigated the effect of glibert mutation on the occurrence of pigment cholelithiasis in Tunisian patients with beta (beta) hemoglobinopathy including sickle cell anemia and beta thalassemia (minor). SUBJECTS AND METHODS: Our study included 151 subjects divided in 75 SCA patients and 76 beta thalassemia patients. Both groups of patients were divided into two sub-groups according to the presence or absence of cholelithiasis. The relationship between A(TA)nTAA variation of UGT1A1 gene, the serum bilirubin level and the occurrence of cholilithiasis was investigated. RESULTS: Our results show a significant association between genotypes carrying variant (TA)7 and hyperbilirubinemia (p<0.05). Furthermore, we demonstrated a significant association between (TA)6/(TA)7 and (TA)7/(TA)7 genotypes with cholelithiasis among sickle cell anemia and thalassemia patients (p<0.05). CONCLUSION: Altogether, our data provide evidence that genotypes (TA)6/(TA)7 and (TA)7/(TA)7 and (TA)7 variant present a risk factor of developing gallstone among beta hemoglobinopathy Tunisian patients. PMID- 26375742 TI - [Adjuvant chemotherapy in colon cancer. About 119 cases]. AB - BACKGROUND: colon cancer is a public health problem worldwide and in Tunisia. The prognosis of patients with unresectable colorectal cancer varies according to the stage. The indication for adjuvant chemotherapy is well established in the colon cancer stage III, while it remains a matter of controversy for stage II. The aim of this work is to identify the epidemiological and anatomoclinical assess therapeutic outcomes in terms of overall survival of patients with high-risk stage II and stage III colon cancer treated with surgery and adjuvant chemotherapy. METHODS: DS: It's a retrospective study based on 119 patients with colon adenocarcinoma from 1996 to 2010. This patients suffering from colon cancer classified stage II and III having them all radical surgery and adjuvant chemotherapy. RESULTS: The average age of our patients was 53 years. The surgery was performed in an emergency situation in 53 patients (44%). Stages II and III, respectively, were observed in 47% and 53% of cases. Three regimens of chemotherapy were used: protocol FUFOL (50%), followed by FOLFOX (34%) and the protocol LV5FU2 (16%). Overall survival of patients all stages combined was 73.4% at 5 years. Stage III of the TNM classification (p = 0.03) and the number of cycles of chemotherapy <6 (p=0.02) were a negative prognostic factors influencing overall survival. Patients stage III treated with FOLFOX chemotherapy type had a better survival than those treated with chemotherapy type LV5FU2 or FUFOL with a significant difference (p= 0.05). CONCLUSION: Our results are consistent with those in the literature. The prognosis of colon cancer is improving thanks to recent advances that have enabled the integration of new cytogenetic factors in the therapeutic decision. PMID- 26375743 TI - [Diagnostic accuracy, limits and practical implications of Multidetector Computed Tomography Coronarography. About 105 cases]. AB - BACKGROUND: Non-invasive examination of coronary artery disease is an attractive and rapidly evolving possibility. In certain clinical situations ,multi-detector computed tomography coronarography (MDCT) is currently considered as a promising technique alternative to conventional coronary angiography (CCA). PURPOSE: We suggest from our personal study and from a review of the literature, to analyze diagnostic accuracy of MDCT , its limits and to deduct, its practical implications and its indications. METHODS: 105 patients underwent 64-slice MDCT . Coronary angiography was performed every time when the MDCT was pathologic. In two cases the MDCT was realized in complement of inconclusive coronary angiography .Study of coronary arteries was based on "per -segment" and "per- patients" analyse Results : The mean age was 63,3 years., sex ratio was 0 ,7. Hypertension was noted in 63% of cases 29 ,9 % of patients had mellitus diabetes.The initial clinical presentation was unusual chest pain in 46 patients, exercise chest pain in 40 cases. the MDCT was done for the detection of silent ischemia In 5 cases, for screening of CAD in patients with dilated cardiomyopathy in 5 cases , before cardiac surgery in 3 case and before non cardiac surgery in 2 cases. MDCT was normal in 30 patients ( 28% ) so coronary angiography was avoided in 60% of patients with unusual chest pain, and in 50% of patients with dilated cardiomyopathy and in also in 50% of patients selected for cardiac or non cardiac surgery. In per-segment study the sensitivity, specificity, positive and negative predictive value of the MDCT in detecting coronary stenosis were respectively 89 %,98% , 91% and 97% versus, 98%,89%,94%, 95% the per-patient evaluation .The MDCT was inclusive in10 patients because .of calcifications in 8 cases and because uncontrolled unchecked heart rate in 40 cases Conclusion : our results for negative predictive value of MDCT are similar to reports from the literature. This suggests that in this clinical setting , MDCT may replace coronary in patients with low probability of coronary artery diseases, its is also useful for assessment of cardiomyopathy and before cardiac or non cardiac surgery. PMID- 26375744 TI - [Primary manifestation of small Lymphocytic Lymphoma in the Prostate: A case report]. AB - We report a case of Lymphocytic Lymphoma presenting with primary manifestation in the prostate. A 82 year-old man presented to emergency department with acute urinary retention. Digital rectal examination revealed a voluminous and firm prostate. Histology confirmed involvement of the prostate by small B Lymphocytic Lymphoma. The patient was treated with chlorambucil. Lymphocytic infiltration of prostate is a rare manifestation. However this may also be the first sign of an undiagnosed lymphoma. This observation shows that the prostatic lymphoma must be considered among the causes of low urinary retention. PMID- 26375745 TI - [Fatal pulmonary mycosis in a diabetic and cirrhotic patient]. AB - Pulmonary mucormycosis is a rare, devastating, opportunistic fungal infection, caused by the ubiquitous filamentous fungi of the Mucorales order of the class of Zygomycetes. This infection occurs principally in some particular conditions, specially in diabetic patients and immunocompromised host, and rarely in cirrhotic patients. The diagnosis of mucormycosis can only be confirmed by pathological and mycological examination of biopsy specimens. We report a case of pulmonary mucormycosis in a 68-year-old woman with underlying liver cirrhosis and diabetes mellitus. Endoscopic and radiologic findings supported the diagnosis of hydatid cyst of the lung. The patient underwent surgical resection and was started on amphotericin B, after pathological examination. Unfortunately, she succumbed to the infection within one month of surgery. PMID- 26375747 TI - Pediatric Primary splenic angiosarcoma: A very rare disease. AB - The primary splenic angiosarcoma is a rare and aggressive tumor. Diagnose primarily in adults over 40 years. There were less than ten pediatric cases reported. A 13-year-old presented to the emergency with left upper quadrant pain. Laboratory results revealed anemia (11.3 g / dL) with normal platelets (166. 109 / L). A heterogeneous formation with a major axis of 5 cm has been identified on the scan of the abdomen. Splenectomy by a laparotomy was performed, and angiosarcoma Primary splenic was discovered. Seven months later, a scanner control showed no progressive disease, in particular, no liver metastases. She is currently alive without signs of progression. The primary splenic angiosarcoma is almost universally fatal, despite treatment. The best chance of survival is early diagnosis and splenectomy before the breaking of the spleen. PMID- 26375746 TI - [FT4 immunoassay interference : A case report]. AB - Measurement of thyrotropin and free thyroxin made using immunoassays are usually needed in clinical endocrinology. Here, we report a case of a patient with type 2 diabetes who presented a weight loss. To eliminate hyperthyroidism, thyroid function tests were performed. Free thyroxin (FT4) was decreased using two automated immunoassays TOSOH AIA 1800 and Roche ELECSYS 2010, with a normal thyrotropin value. Thyroid function tests repeated a month later were normal. The patient's history revealed contact with sheep, which may partly explain the interference. Investigations into the patient's serum were carried out using both the PEG test and dilution test. Interference factors were probably antibodies. Despite progress in immunoassays, we should be aware of interference occurrence since it can lead to false results, unnecessary investigations and incorrect treatment. Thus, simple tests must be carried out as if interference in immunoassays were suspected. Dilutions and PEG tests are generally performed as first line investigations. PMID- 26375748 TI - [Hibernoma of the thigh. A case report]. PMID- 26375749 TI - Bilateral exudative retinal detachment secondary to bilateral choroidal metastasis of breast cancer. PMID- 26375750 TI - Atypical forms of pulmonary sarcoidosis: A diagnostic not to ignore. PMID- 26375751 TI - [Intestinal obstruction caused by migration of intragastric balloon. A case report]. PMID- 26375752 TI - [Frantz tumor in a child]. PMID- 26375753 TI - Diagnosis of pulmonary sequestration: Contribution of the CT scan. PMID- 26375754 TI - [Paraneoplastic dermatomyositis: About an exceptional location]. PMID- 26375755 TI - [Tolerance induction protocol in hypersensitivity reaction to antituberculosis drugs]. PMID- 26375756 TI - Calcium and Phosphorus Detection Using Benchtop Versus Handheld X-ray Fluorescence Spectrometers. AB - Elemental analysis of calcium (Ca) and phosphorus (P) has been shown to be useful in differentiating skeletal and nonskeletal material. X-ray fluorescence spectrometry (XRF) is an attractive, nondestructive technique for forensic anthropologists, and the development of portable XRF instrumentation is promising for field applications. This study examines the performance of handheld XRF instrumentation operated in air compared to a traditional benchtop XRF device that has the ability to control the analysis atmosphere. Both instruments can be used to effectively distinguish skeletal from nonskeletal remains. However, as the measurement atmosphere affects detection levels for calcium and phosphorus, Ca/P ratios obtained from the instruments and analysis conditions were found to differ significantly, with analyses conducted in air showing significantly lower phosphorus detection. Consequently, comparison of Ca/P ratios to conclude skeletal versus nonskeletal origin must be based on data collected under similar analysis conditions. PMID- 26375757 TI - Curcumin inhibits lymphangiogenesis in vitro and in vivo. AB - SCOPE: Curcumin, a dietary compound from turmeric, has potent antimetastatic effects; however, the underlying mechanisms are not well understood. The aim of this study is to investigate the effects and mechanisms of curcumin on lymphangiogenesis (formation of new lymphatic vessels), which plays a critical role in tumor metastasis. METHODS AND RESULTS: Curcumin inhibited vascular endothelial growth factor-C (VEGF-C) induced lymphangiogenesis in a Matrigel plug assay in mice, and VEGF-C induced tube formation in human dermal lymphatic endothelial cells, demonstrating its antilymphangiogenic action in vivo and in vitro. Curcumin inhibited lymphangiogenesis, in part through suppression of proliferation, cell-cycle progression and migration of lymphatic endothelial cells, while it had little effect on matrix metalloproteinase activities. Curcumin inhibited expressions of VEGF receptors (VEGFR2 and VEGFR3), as well as downstream signaling such as phosphorylation of ERK and FAK. Finally, curcumin sulfate and curcumin glucuronide, which are two major metabolites of curcumin in vivo, had little inhibitory effect on proliferation of human dermal lymphatic endothelial cells. CONCLUSION: Our results demonstrate that curcumin inhibits lymphangiogenesis in vitro and in vivo, which could contribute to the antimetastatic effects of curcumin. PMID- 26375759 TI - Associations among time-average mineral values, mortality and cardiovascular events in hemodialysis patients. AB - Mineral and bone disease (CKD-MBD), disorders of mineral metabolism, is associated with mortality and cardiovascular disease in dialysis patients. However, the associations among time average mineral values (P, Ca and PTH) and clinical outcomes are not well investigated. OBJECTIVES: This study examines the associations among mineral values and clinical outcomes from a single medical center. METHODS: Adult patients who initiate hemodialysis in Taoyuan General Hospital from 2008 to 2013 were enrolled. We examined these associations using baseline and time-average model. The clinical outcomes included mortality, major adverse cardiovascular events (MACE) and cardiovascular events. We also examined the association between achieve K/DOQI guidelines' targets and clinical outcomes. RESULTS: From a total of 284 hemodialysis patients, none of the baseline mineral values is associated with mortality and cardiovascular event, except hyperphosphatemia. Compared to patients achieved K/DOQI guidelines' targets, time average hyperphosphatemia is associated with MACE and first cardiovascular event [the adjusted hazard ratios (AHRs) are 6.343 and 3.278); whereas time average hypercalcemia is associated with MACE marginally (the AHR is 5.964). None of above clinical outcomes is related to hyperparathyroidism. The AHRs for mortality in those who only met PTH targets and none of the mineral value targets are 1.73 and 1.74, whereas the AHRs for cardiovascular events in those who met only Ca, only PTH, and none of the targets are 1.73, 1.81 and 2.54 (all ps < 0.05). CONCLUSION: Time-average phosphate is associated with cardiovascular events after initiation of dialysis. Among mineral values, serum phosphate is still the strongest predictor for mortality and cardiovascular events. PMID- 26375758 TI - Nanovesicles of nitrendipine with lipid complex for transdermal delivery: pharmacokinetic and pharmacodynamic studies. AB - CONTEXT: Vesicular transdermal delivery can enhance the bioavailability of a drug especially affected by first-pass metabolism, e.g. nitrendipine. However effective transdermal delivery employs permeation enhancer, e.g oleic acid (OA) with ceramide 2, stearic acid, behenic acid, and cholesteryl sulfate lipid complex. OBJECTIVE: This study investigated the preparation, characterization of physicochemical properties, ex vivo permeation using human skin, pharmacokinetic parameters and antihypertensive potential in rats, of nitrendipine-loaded nanovesicles of ceramide 2, stearic acid, behenic acid and cholesteryl sulfate containing oleic acid gel (NOVG). MATERIALS AND METHODS: The nanovesicles were made using film hydration method and characterized for physicochemical properties, ex vivo permeation using human skin, pharmacokinetic parameters and antihypertensive potential. RESULTS: Nitrendipine-loaded nanovesicles of ceramide 2 containing oleic acid (NOV-5) have shown fluxes in the range of 4.88-24.72 MUg/cm(2)/h nitrendipine oral suspension (NOS) at equal dose. NOVG-5 has shown almost 33% reduction in blood pressure in the first hour and a further decrease of 25% in the second hour to restore the normal pressure. DISCUSSION: The permeation increases with increase in OA content. OA gets integrated in vesicle wall and enhances its permeability, whereas ceramide content makes sure that skin does not become damaged even after permeation. CONCLUSION: NOVG-5 has shown the most favorable physicochemical properties and good permeation through skin providing good management of hypertension during crucial initial hours. PMID- 26375760 TI - Scattering based hyperspectral imaging of plasmonic nanoplate clusters towards biomedical applications. AB - A new optical scattering contrast-agent based on polymer-nanoparticle encapsulated silver nanoplates (PESNs) is presented. Silver nanoplates were chosen due to the flexibility of tuning their plasmon frequencies. The polymer coating preserves their physical and optical properties and confers other advantages such as controlled contrast agent delivery. Finite difference time domain (FDTD) simulations model the interaction of light with the nanoplates in different orientations in the cluster. Hyperspectral dark field microscopy (HYDFM) observes the scattering spectra of the PESNs. An unsupervised sequential maximum angle convex cone (SMACC) image analysis resolves spectral endmembers corresponding to different stacking orientations of the nanoplates. The orientation-dependent endmembers qualitatively agree with the FDTD results. For contrast enhancement, the uptake and spatial distribution of PESNs are demonstrated by an HYDFM study of single melanoma cells to result in an enhanced contrast of up to 400%. A supervised spatial mapping of the endmembers obtained by the unsupervised SMACC algorithm reveals spatial distributions of PESNs with various clustering orientations of encapsulated nanoplates. Our study demonstrates tunability in plasmonics properties in clustered metal nanoparticles and its utility for the development of scatter-based imaging contrast agents for a broad range of applications, including studies of single cells and other biomedical systems. PMID- 26375761 TI - Mammalian phospholipid homeostasis: homeoviscous adaptation deconstructed by lipidomic data driven modelling. AB - One of the mostly widely cited theories of phospholipid homeostasis is the theory of homeoviscous adaptation (HVA). HVA states that cells maintain membrane order (frequently discussed in terms of membrane fluidity or viscosity) within tight conditions in response to environmental induced changes in membrane lipid composition. In this article we use data driven modelling to investigate membrane order, using methodology we previously developed to investigate another theory of phospholipid homeostasis, the intrinsic curvature hypothesis. A set of coarse grain parameters emerge from our model which can be used to deconstruct the relative contribution of each component membrane phospholipid to net membrane order. Our results suggest, for the membranes in the mammalian cells we have studied, that a ratio control function can be used to model membrane order. Using asynchronous cell lines we quantify the relative contribution of around 130 lipid species to net membrane order, finding that around 16 of these phospholipid species have the greatest effect in vivo. Then using lipidomic data obtained from partially synchronised cultures of HeLa cells we are able to demonstrate that these same 16 lipid species drive the changes in membrane order observed around the cell cycle. Our findings in this study suggest, when compared with our previous work, that cells maintain both membrane order and membrane intrinsic curvature within tight conditions. PMID- 26375762 TI - MR-based conductivity imaging using multiple receiver coils. AB - PURPOSE: To propose a signal combination method for MR-based tissue conductivity mapping using a standard clinical scanner with multiple receiver coils. METHODS: The theory of the proposed method is presented with two practical approaches, a coil-specific approach and a subject-specific approach. Conductivity maps were reconstructed using the transceive phase of the combined signal. The sensitivities of the coefficients used for signal combination were analyzed and the method was compared with other signal combination methods. For validation, multiple receiver brain coils and multiple receiver breast coils were used in phantom, in vivo brain, and in vivo breast studies. RESULTS: The variation among the conductivity estimates was <15% as determined by the coefficient sensitivity tests. Compared with other signal combination methods, the proposed method yielded fewer artifacts in the conductivity estimates. CONCLUSION: MR-based tissue conductivity mapping is feasible when using a standard clinical MR scanner with multiple receiver coils. The proposed method reduces systematic errors in phase-based conductivity mapping that can occur due to the inhomogeneous magnitude of the combined receive profile. Magn Reson Med 76:530-539, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26375763 TI - Associating portal embolization and artery ligation to induce rapid liver regeneration in staged hepatectomy. AB - BACKGROUND: Insufficient volume of the future liver remnant (FLR) is a major cause of unresectability in patients with bilobar colorectal liver metastases (CLM). The objective of this study was to evaluate the safety and efficacy of the novel associating portal embolization and artery ligation (APEAL) technique before extended right hepatectomy during a two-stage procedure for CLM. METHODS: All patients who had undergone extended right hepatectomy during two-stage surgery for CLM between 2012 and 2014 were identified retrospectively from a prospectively maintained database. In the first stage, right portal vein embolization, partial right hepatic artery ligation and devascularization of segment IVb along the round ligament without parenchymal transection were associated with clearance of the FLR and/or primary tumour resection. Liver volumetry was performed using OsiriX software on postoperative day (POD) 7 and 30. RESULTS: Ten patients underwent the APEAL procedure. During the first stage, APEAL was combined with colorectal resection in seven patients. The median (range) interval between the two stages was 45 (31-71) days. The FLR volume increased from 327 (214-537) cm(3) before surgery to 590 (508-1072) cm(3) on POD 7 and 701 (512-1018) cm(3) on POD 30. This corresponded to a FLR regeneration rate of 104 (42-185) and 134 (53-171) per cent respectively. There were no deaths. The overall morbidity rate was 60 per cent (6 of 10) after each procedure, with severe morbidity occurring in two and three of ten patients after the first and second procedures respectively. CONCLUSION: APEAL induces fast, safe, reproducible and effective FLR growth when an extended right hepatectomy is scheduled in patients with multiple bilobar CLM. PMID- 26375764 TI - Oncologic Phenotype of Peripheral Neuroblastic Tumors Associated With PHOX2B Non Polyalanine Repeat Expansion Mutations. AB - BACKGROUND: Germline non-polyalanine repeat expansion mutations in PHOX2B (PHOX2B NPARM) predispose to peripheral neuroblastic tumors (PNT), frequently in association with other neurocristopathies: Hirschsprung disease (HSCR) or congenital central hypoventilation syndrome (CCHS). Although PHOX2B polyalanine repeat expansions predispose to a low incidence of benign PNTs, the oncologic phenotype associated with PHOX2B NPARM is still not known in detail. METHODS: We analyzed prognostic factors, treatment toxicity, and outcome of patients with PNT and PHOX2B NPARM. RESULTS: Thirteen patients were identified, six of whom also had CCHS and/or HSCR, one also had late-onset hypoventilation with hypothalamic dysfunction (LO-CHS/HD), and six had no other neurocristopathy. Four tumours were "poorly differentiated," and nine were differentiated, including five ganglioneuromas, three ganglioneuroblastomas, and one differentiating neuroblastoma, hence illustrating that PHOX2B NPARM are predominantly associated with differentiating tumors. Nevertheless, three patients had stage 4 and one patient had stage 3 disease. Segmental chromosomal alterations, correlating with poor prognosis, were found in all the six tumors analyzed by array-comparative genomic hybridization. One patient died of tumor progression, one is on palliative care, one died of hypoventilation, and 10 patients are still alive, with median follow-up of 5 years. CONCLUSIONS: Based on histological phenotype, our series suggests that heterozygous PHOX2B NPARM do not fully preclude ganglion cell differentiation in tumors. However, this tumor predisposition syndrome may also be associated with poorly differentiated tumors with unfavorable genomic profiles and clinically aggressive behaviors. The intrafamilial variability and the unpredictable tumor prognosis should be considered in genetic counseling. PMID- 26375766 TI - From the Editor-in-Chief's Desk. PMID- 26375765 TI - Hemoglobin switching's surprise: the versatile transcription factor BCL11A is a master repressor of fetal hemoglobin. AB - The major disorders of beta-globin, sickle cell disease and beta-thalassemia, may be ameliorated by expression of the fetal gene paralog gamma-globin. Uncertainty regarding the mechanisms repressing fetal hemoglobin in the adult stage has served as a puzzle of developmental gene regulation as well as a barrier to rational therapeutic design. Recent genome-wide association studies implicated the zinc-finger transcriptional repressor BCL11A in fetal hemoglobin regulation. Extensive genetic analyses have validated BCL11A as a potent repressor of fetal hemoglobin level. Studies of BCL11A exemplify how contextual gene regulation may often be the substrate for trait-associated common genetic variation. These discoveries have suggested novel rational approaches for the beta-hemoglobin disorders including therapeutic genome editing. PMID- 26375768 TI - A Promising Preliminary Study of Aripiprazole for Treatment-Resistant Childhood Obsessive-Compulsive Disorder. AB - BACKGROUND: Obsessive-compulsive disorder (OCD) is a relatively frequent disease in childhood, which is generally treated with selective serotonin reuptake inhibitors (SSRIs) and/or clomipramine and cognitive behavioral therapy (CBT). However, nearly half of the cases are treatment resistant. Aripiprazole was shown to be beneficial in augmentation therapy in treatment-refractory OCD. This study evaluated its effectiveness as a single agent in these cases. METHODS: Sixteen children (nine girls, seven boys), who were nonresponders to treatment with at least two types of SSRIs and CBT, were administered 12 weeks of aripiprazole treatment with a mean dose of 4.75 mg/day (range: 2-7.5 mg/day). Treatment outcomes were evaluated by the Childhood Yale-Brown Obsessive Compulsive Scale (CY-BOCS), and the Clinical Global Impressions-Severity and Improvement (CGI-S and CGI-I) scales. RESULTS: Children with a mean age of 10.9+/-2.9 years had severe obsessive compulsive symptoms at baseline, and >80% of them had another comorbid psychiatric disease. Significant improvements in symptoms were achieved after 12 weeks of aripiprazole treatment, which were evaluated by significant decreases in symptom scores in the CY-BOCS, and improvements in CGI-I scores. CONCLUSIONS: This very small study of aripiprazole, given to children with OCD resistant to at least 12 weeks treatment with at least two SSRIs and CBT, demonstrated striking improvement in CGI scores (all subsets, p<=0.002) for 13 of 16 children, and halved all CY-BOCS subscores after ~12 weeks of treatment. PMID- 26375767 TI - Outcome of Youth with Early-Phase Schizophrenia-Spectrum Disorders and Psychosis Not Otherwise Specified Treated with Second-Generation Antipsychotics: 12 Week Results from a Prospective, Naturalistic Cohort Study. AB - OBJECTIVES: The purpose of this study was to assess differences in the outcomes of youth with schizophrenia-spectrum disorders (SCZ-S) and psychotic disorder not otherwise specified (PsyNOS) during early antipsychotic treatment. METHODS: The study was a prospective, naturalistic, inception cohort study of youth <=19 years old with SCZ-S (schizophrenia, schizoaffective disorder, schizophreniform disorder) or PsyNOS (PsyNOS, brief psychotic disorder) and <=24 months of lifetime antipsychotic treatment receiving clinician's choice antipsychotic treatment. Baseline demographic, illness and treatment variables, and effectiveness outcomes were compared at 12 weeks last-observation-carried-forward across SCZ-S and PsyNOS patients, adjusting for significantly different baseline variables. RESULTS: Altogether, 130 youth with SCZ-S (n=42) or PsyNOS (n=88), mostly antipsychotic naive (76.9%), were prescribed risperidone (47.7%), olanzapine (19.2%), aripiprazole (14.6%), quetiapine (11.5%), or ziprasidone (6.9%). Compared with those with PsyNOS, SCZ-S youth were older (16.4+/-2.1 vs. 14.8+/-3.2, p=0.0040), and less likely to be Caucasian (19.1% vs. 42.5%, p=0.009). At baseline, SCZ-S patients had significantly higher Clinical Global Impressions-Severity (CGI-S) scores (6.0+/-0.9 vs. 5.5+/-0.8, p=0.0018) and lower Children's Global Assessment Scale (CGAS) scores (29.6+/-9.2 vs. 36.1+/-8.9, p=0.0002) and were more likely to be in the severely ill CGAS group (i.e., CGAS<=40). SCZ-S and PsyNOS patients did not differ regarding all-cause discontinuation (40.5 vs. 40.3%. p=0.49), discontinuation because of adverse effects (12.2% vs. 12.4%, p=0.97), or nonadherence (29.3% vs. 30.9%, p=0.88), but somewhat more SCZ-S patients discontinued treatment for inefficacy (19.5% vs. 7.4%, p=0.063). CGI-S and CGAS scores improved significantly in both diagnostic groups (p=0.0001, each). Adjusting for baseline differences, PsyNOS patients experienced significantly better CGI-I improvement (CGI-I) scores (p=0.012) and more frequently reached higher categorical CGAS group status (p=0.021) than SCZ-S patients. CONCLUSIONS: Both youth with SCZ-S and those with PsyNOS experienced significant improvements with clinician's choice antipsychotic treatment. However, treatment discontinuation was common within 12 weeks, with greater inefficacy-related discontinuation in the SCZ-S group, whereas CGI-I and CGAS score-based improvements were greater in the PsyNOS group. PMID- 26375770 TI - 25th Anniversary State-of-the-Art Expert Discussion With Tom R. DeMeester, MD, on GERD. PMID- 26375769 TI - Metformin in an Adolescent with Significant Weight Gain. PMID- 26375771 TI - Getting Started with Minimally Invasive Pancreaticoduodenectomy: Is It Worth It? AB - BACKGROUND: This study evaluates the safety and cost of introducing minimally invasive pancreaticoduodenectomy (MIPD) to a surgeon's practice. SUBJECTS AND METHODS: All MIPDs performed between December 2011 and July 2013 were compared with open pancreaticoduodenectomy (OPD) cases by the same surgeon. The primary outcomes were mortality, major morbidity, and re-operation. Secondary outcomes were perioperative and oncologic outcomes and cost. MIPD include total laparoscopic pancreaticoduodenectomy (TLPD) and laparoscopic-assisted pancreaticoduodenectomy (LAPD), where a small incision is used for reconstruction. Bivariate comparisons of outcomes were performed using nonparametric tests. RESULTS: In total, 44 pancreaticoduodenectomies were performed: 15 MIPDs (2 TLPDs and 13 LAPDs) and 29 OPDs. One death occurred in each group. Major complication rates were not significantly different (33% for MIPD versus 17% for OPD); however, there was a trend toward more re-operation after MIPD compared with OPD (20% versus 3%; P = .07). The incidence of pancreatic leak (20% for MIPD versus 14% for OPD), biliary leak (0% versus 7%, respectively), abscess formation (27% versus 14%, respectively), and intraabdominal hemorrhage (13% versus 3%, respectively) were not significantly different. MIPD achieved equivalent oncologic outcomes as OPD with 100% R0 margin and adequate lymph node retrieval. There was no statistical difference in median operative time (342 minutes for MIPD versus 358 minutes for OPD), length of stay (8 versus 9 days, respectively), operating room expenses (Canadian) ($7246.0 versus $6912.0, respectively), or total cost (Canadian) per case ($15,034.0 versus $18,926.0, respectively). CONCLUSIONS: MIPD and OPD had similar safety and cost in this introductory series. However, a trend toward a higher rate of re operation for pancreatic leak suggests the need for caution in introducing this novel technique. PMID- 26375772 TI - Systematic Video Documentation in Laparoscopic Colon Surgery Using a Checklist: A Feasibility and Compliance Pilot Study. AB - BACKGROUND: High-quality images can be readily captured during laparoscopic colon surgery, but there are no guidelines for documentation of these video data or how to best measure surgical quality from an operative video. This study evaluates the feasibility and compliance in documenting key steps during laparoscopic right hemicolectomy and sigmoid colectomy. MATERIALS AND METHODS: A retrospective review of previously recorded videos of patients undergoing laparoscopic right hemicolectomy or sigmoid colectomy from September to December 2011 in a single institution was performed. Patients' demographics, intraoperative features, postoperative complications, and variables for video recording and editing were collected. Compliance of key surgical steps was assessed using a checklist by two independent surgeons. RESULTS: Sixteen laparoscopic operations (seven right hemicolectomies and nine sigmoid colectomies) were recorded. Twelve (75%) were laparoscopic-assisted, and four (25%) were hand-assisted laparoscopic operations. Compliance with key surgical steps in laparoscopic right hemicolectomy and sigmoid colectomy was demonstrated in the majority of patients, with steps ranging in compliance from 42.9% to 100% and from 77.8% to 100%, respectively. The edited video had a median duration of 3 minutes 47 seconds (range, 1 minute 44 seconds-5 minutes 38 seconds) with a production time of nearly 1 hour and a resolution of 1440 * 1080 pixels. CONCLUSIONS: Key surgical steps during laparoscopic right hemicolectomy and sigmoid colectomy can be documented and edited into a short representative video. Standardization of this process should allow video documentation to improve quality in laparoscopic colon surgery. PMID- 26375773 TI - An Endoscopic Surgical Skill Validation System for Pediatric Surgeons Using a Model of Congenital Diaphragmatic Hernia Repair. AB - PURPOSE: We developed a system to objectively verify the endoscopic surgical skills of pediatric surgeons. MATERIALS AND METHODS: We developed a thoracoscopic model of congenital diaphragmatic hernia mimicking a newborn's size. The examinees were divided into Experts (n = 10) and Trainees (n = 19), and each group performed two tasks (Task 1, reduction of a herniated intestine from the thoracic space to the abdomen; Task 2, perform three suture ligatures of a diaphragm defect using intracorporeal knot-tying). The end points were the time required to complete Task 1, time score calculated using the residual time from the time limit for Task 2, number of complete full-thickness sutures, maximum air pressure tolerance, degree of diaphragm deformation, and the residual defect areas after suturing. We also evaluated the total path length and velocity of the forceps tips using a three-dimensional position measurement instrument. RESULTS: The Experts had significantly superior results for the time for Task 1, time score, number of complete full-thickness sutures, maximum air-pressure tolerance, and degree of diaphragm deformation in Task 2 (all P < .05). We found that the total path length and average velocities for the left forceps were inferior to those of the right forceps in both tasks in the Trainees (both P < .05, respectively), whereas the Expert group showed no significant laterality in these tasks. CONCLUSIONS: Our model could validate the quality of endoscopic surgical skills and could differentiate between Expert and Trainee pediatric surgeons. The Experts could use their forceps equally well to perform tasks even in a small working space. PMID- 26375774 TI - An ethnobotanical survey of traditionally used plants on Suva planina mountain (south-eastern Serbia). AB - ETHNOPHARMACOLOGICAL RELEVANCE: This study documents the ethnobotanical and ethnomedicinal importance of plants in the Suva planina mountain region (south eastern Serbia). It is reflected in their high diversity and their wide range of uses in the treatment of the local population. The aim of this study was a comparative analysis of data collected in the Suva planina region with relevant data from the Western Balkans, which included identifying the 'most popular' plants, as well as those species which are used specifically for treatment solely in the research area. MATERIALS AND METHODS: Ethnobotanical research was carried out between 2012 and 2014 and data was collected through both open and semi structured interviews with locals. A total of 66 people were interviewed (37 women and 29 men), aged between 49 and 90 (with a mean age of 71). RESULTS: This study identified 128 plants and 2 fungi which are used in ethnomedicine, 5 plant species used in ethnoveterinary medicine, and 16 plants used for 'other' purposes. Lamiaceae (20), Asteraceae (17), Rosaceae (16), Brassicaceae (5), Alliaceae (4) and Apiaceae (4) have the greatest diversity of species. Results showed that Achillea mellefolium, Allium cepa, Allium sativum, Arctostaphyllos uva-ursi, Gentiana lutea, Hypericum perforatum, Juglans regia, Matricaria chamomilla, Mentha piperita, Plantago lanceolata, Plantago major, Salvia officinalis, Sempervivum tectorum, Tilia cordata and Thymus sepyllum are the 'most popular' medicinal plants (UV=1). Those plants with the most phytotherapeutic uses are Gentiana cruciata (14), H. perforatum (11) and A. sativum (10), while the most common conditions treated with medicinal plants are respiratory (79), urogenital (53), gastrointestinal (51), skin (43) and those relating to the circulatory system (35). A comparative analysis of the data collected in the research area and that from other parts of the Western Balkans showed that there are great similarities within Serbia between Suva planina and the Zlatibor region (37.2%) and Kopaonik Mt. (32.3%), while further afield it is most similar to Bosnia and Herzegovina (40.9%) and Bulgaria (40.6%). Moreover, it was established that 14 plant species and 2 fungi are used only in the Suva planina region, which points to the specificity of the diversity and the sound knowledge of medicinal plants in this region. CONCLUSIONS: Our results confirm that medicinal plants are an invaluable resource of the research area and need to be protected as they contribute to an improvement in living standards and the survival of people threatened by unfavourable demographic trends. However, due to over-exploitation, some plants have become exceptionally rare and are under threat, leading to the need for their rational use and protection so as to ensure they are still around for future generations. PMID- 26375775 TI - Melkersson-Rosenthal syndrome. PMID- 26375776 TI - Blood examination is necessary for oral mucosal disease patients. PMID- 26375777 TI - Long-term follow up and predictive factors for successful outcome of transurethral incision of the bladder neck in women with detrusor underactivity. AB - BACKGROUND/PURPOSE: Detrusor underactivity (DU) is a common urologic problem. Our previous study revealed the transurethral incision of the bladder neck (TUI-BN) improves short-term voiding efficiency (VE) in female patients with DU. This study focused on the long-term outcomes of TUI-BN and identified the predictive factors of satisfactory outcomes. METHODS: A total 50 women with DU for whom medical treatment failed underwent TUI-BN. The urodynamic parameters at baseline and follow-up visits were analyzed. Patients with VEs >50% were considered to have satisfactory outcomes. Baseline urodynamic parameters were analyzed as factors predictive of outcomes. RESULTS: After a mean follow up of 61.8 months, 26 of 50 patients had satisfactory outcomes. The mean VE, maximum flow rate, voided volume, detrusor pressure, and postvoid residual volume significantly improved after TUI-BN. A higher intravesical pressure [Pves, odds ratio (OR) = 1.023, p = 0.013] and smaller first sensation of bladder filling (OR = 0.990, p = 0.020) at baseline were predictive factors for satisfactory outcomes. The multivariate analysis revealed that only baseline Pves was a significant predictor of satisfactory outcomes (OR = 1.024, p = 0.038). The receiver operating characteristic curve analysis of baseline Pves showed that the area under the curve was 0.767 (95% confidence interval = 0.624-0.876). The optimal cutoff value of Pves for a satisfactory outcome was 45 cmH2O, which had a specificity of 78.26% and acceptable sensitivity of 73.08%. CONCLUSION: TUI-BN improved VE in women with DU over the long term. A higher Pves compared to a lower Pves was predictive of satisfactory surgical outcomes. PMID- 26375778 TI - Epidemiology of sexually transmitted viral hepatitis in human immunodeficiency virus-positive men who have sex with men in Asia. AB - Both human immunodeficiency virus (HIV) and viral hepatitis constitute major disease burden globally. As with other parts of the world, the HIV epidemic in Asia impacts mainly on men who have sex with men, one of the at-risk populations for sexually transmitted viral hepatitis. With the increasing availability of effective antiretroviral therapy, HIV-related mortality of people living with HIV has markedly reduced. Liver disease has become an important cause of mortality and morbidity in the HIV-infected population. With the improvement of socioeconomic conditions and availability of healthcare in Asian countries in recent years, the epidemiology of sexually transmitted viral hepatitis among HIV positive men who have sex with men has also evolved. This review updates the epidemiology of different types of sexually transmitted viral hepatitis in this defined population in Asia. PMID- 26375779 TI - Presence of aliphatic and polycyclic aromatic hydrocarbons in near-surface sediments of an oil spill area in Bohai Sea. AB - In order to determine the source of organic matter and the fingerprint of the oil components, 50 samples collected from the near-surface sediments of the oil spill area in Bohai Sea, China, were analyzed for grain size, total organic carbon, aliphatic hydrocarbons (AHs), and polycyclic aromatic hydrocarbons (PAHs). The concentrations of C15-35 n-alkanes and 16 United States Environmental Protection Agency (US EPA) priority pollutant PAHs were found in the ranges of 0.88-3.48MUg g(-1) and 9.97-490.13ng/g, respectively. The terrestrial organic matters characterized by C27-C35 n-alkanes and PAHs, resulting from the combustion of higher plants, are dominantly contributed from the transportation of these plants by rivers. Marine organic matters produced from plankton and aquatic plants were represented by C17-C26 n-alkanes in AHs. Crude oil, characterized by C17-C21 n alkanes, unresolved complex mixture (UCM) with a mean response factor of C19 n alkanes, low levels of perylene, and a high InP/(InP+BghiP) ratio, seeped into the oceans from deep hydrocarbon reservoirs, as a result of geological faults. PMID- 26375781 TI - Adaptive memory: Animacy enhances free recall but impairs cued recall. AB - Recent research suggests that human memory systems evolved to remember animate things better than inanimate things. In the present experiments, we examined whether these effects occur for both free recall and cued recall. In Experiment 1, we directly compared the effect of animacy on free recall and cued recall. Participants studied lists of objects and lists of animals for free-recall tests, and studied sets of animal-animal pairs and object-object pairs for cued-recall tests. In Experiment 2, we compared participants' cued recall for English English, Swahili-English, and English-Swahili word pairs involving either animal or object English words. In Experiment 3, we compared participants' cued recall for animal-animal, object-object, animal-object, and object-animal pairs. Although we were able to replicate past effects of animacy aiding free recall, animacy typically impaired cued recall in the present experiments. More importantly, given the interactions found in the present experiments, we conclude that some factor associated with animacy (e.g., attention capture or mental arousal) is responsible for the present patterns of results. This factor seems to moderate the relationship between animacy and memory, producing a memory advantage for animate stimuli in scenarios where the moderator leads to enhanced target retrievability but a memory disadvantage for animate stimuli in scenarios where the moderator leads to impaired association memory. PMID- 26375780 TI - Identification of protein-protein binding sites by incorporating the physicochemical properties and stationary wavelet transforms into pseudo amino acid composition. AB - With the explosive growth of protein sequences entering into protein data banks in the post-genomic era, it is highly demanded to develop automated methods for rapidly and effectively identifying the protein-protein binding sites (PPBSs) based on the sequence information alone. To address this problem, we proposed a predictor called iPPBS-PseAAC, in which each amino acid residue site of the proteins concerned was treated as a 15-tuple peptide segment generated by sliding a window along the protein chains with its center aligned with the target residue. The working peptide segment is further formulated by a general form of pseudo amino acid composition via the following procedures: (1) it is converted into a numerical series via the physicochemical properties of amino acids; (2) the numerical series is subsequently converted into a 20-D feature vector by means of the stationary wavelet transform technique. Formed by many individual "Random Forest" classifiers, the operation engine to run prediction is a two layer ensemble classifier, with the 1st-layer voting out the best training data set from many bootstrap systems and the 2nd-layer voting out the most relevant one from seven physicochemical properties. Cross-validation tests indicate that the new predictor is very promising, meaning that many important key features, which are deeply hidden in complicated protein sequences, can be extracted via the wavelets transform approach, quite consistent with the facts that many important biological functions of proteins can be elucidated with their low frequency internal motions. The web server of iPPBS-PseAAC is accessible at http://www.jci-bioinfo.cn/iPPBS-PseAAC , by which users can easily acquire their desired results without the need to follow the complicated mathematical equations involved. PMID- 26375782 TI - The spatial scaffold: The effects of spatial context on memory for events. AB - Events always unfold in a spatial context, leading to the claim that it serves as a scaffold for encoding and retrieving episodic memories. The ubiquitous co occurrence of spatial context with events may induce participants to generate a spatial context when hearing scenarios of events in which it is absent. Spatial context should also serve as an excellent cue for memory retrieval. To test these predictions, participants read event scenarios involving a highly familiar or less familiar spatial context, or person, which they were asked to imagine and remember. At recall, locations were more effective memory cues than people, and both were better when they were highly familiar. Most importantly, when no locations were specified at study, participants exhibited a spontaneous tendency to generate a spatial context for the scenarios, while rarely generating a person. Events with spatial context were remembered more vividly and described in more detail than those without. Together, the results favor the view that spatial context plays a leading role in remembering events. PMID- 26375783 TI - Detection of the number of changes in a display in working memory. AB - Here we examine a new task to assess working memory for visual arrays in which the participant must judge how many items changed from a studied array to a test array. As a clue to processing, on some trials in the first 2 experiments, participants carried out a metamemory judgment in which they were to decide how many items were in working memory. Trial-to-trial fluctuations in these working memory storage judgments correlated with performance fluctuations within an individual, indicating a need to include trial-to-trial variation within capacity models (through either capacity fluctuation or some other attention parameter). Mathematical modeling of the results achieved a good fit to a complex pattern of results, suggesting that working memory capacity limits can apply even to judgments that involve an entire array rather than just a single item that may have changed, thus providing the expected conscious access to at least some of the contents of working memory. PMID- 26375784 TI - Quantification, prediction, and the online impact of sentence truth-value: Evidence from event-related potentials. AB - Do negative quantifiers like "few" reduce people's ability to rapidly evaluate incoming language with respect to world knowledge? Previous research has addressed this question by examining whether online measures of quantifier comprehension match the "final" interpretation reflected in verification judgments. However, these studies confounded quantifier valence with its impact on the unfolding expectations for upcoming words, yielding mixed results. In the current event-related potentials study, participants read negative and positive quantifier sentences matched on cloze probability and on truth-value (e.g., "Most/Few gardeners plant their flowers during the spring/winter for best results"). Regardless of whether participants explicitly verified the sentences or not, true-positive quantifier sentences elicited reduced N400s compared with false-positive quantifier sentences, reflecting the facilitated semantic retrieval of words that render a sentence true. No such facilitation was seen in negative quantifier sentences. However, mixed-effects model analyses (with cloze value and truth-value as continuous predictors) revealed that decreasing cloze values were associated with an interaction pattern between truth-value and quantifier, whereas increasing cloze values were associated with more similar truth-value effects regardless of quantifier. Quantifier sentences are thus understood neither always in 2 sequential stages, nor always in a partial incremental fashion, nor always in a maximally incremental fashion. Instead, and in accordance with prediction-based views of sentence comprehension, quantifier sentence comprehension depends on incorporation of quantifier meaning into an online, knowledge-based prediction for upcoming words. Fully incremental quantifier interpretation occurs when quantifiers are incorporated into sufficiently strong online predictions for upcoming words. PMID- 26375785 TI - Toolbox or adjustable spanner? A critical comparison of two metaphors for adaptive decision making. AB - For multiattribute decision tasks, different metaphors exist that describe the process of decision making and its adaptation to diverse problems and situations. Multiple strategy models (MSMs) assume that decision makers choose adaptively from a set of different strategies (toolbox metaphor), whereas evidence accumulation models (EAMs) hold that a uniform mechanism is employed but is adapted to the environmental change (adjustable spanner metaphor). Despite recent claims that the frameworks are hard to disentangle empirically, both metaphors make distinct predictions concerning the information acquisition behavior, namely, that search is terminated according to the selected strategy (MSMs) or that information is acquired until an evidence threshold is passed (EAMs). In 3 experiments, we contrasted these predictions by providing participants with different degrees of evidence in a half-open/half-closed information board. For the majority of participants, we find that their stopping behavior is well captured by the notion of an evidence threshold that is either undercut or passed by the given evidence. PMID- 26375786 TI - Context-Dependent Learning in People With Parkinson's Disease. AB - Context-dependent learning is a phenomenon in which people demonstrate superior performance in the context in which they originally learned a skill but perform less well in a novel context. This study investigated context-dependent learning in people with Parkinson's disease (PD) and age-matched nondisabled adults. All participants practiced 3 finger sequences, each embedded within a unique context (colors and locations on a computer screen). One day after practice, the participants were tested either under the sequence-context associations remained the same as during practice, or the sequence-context associations were changed (SWITCH). Compared with nondisabled adults, people with PD demonstrated significantly greater decrement in performance (especially movement time) under the SWITCH condition, suggesting that individuals with PD are more context dependent than nondisabled adults. PMID- 26375788 TI - Macrolides and respiratory infection in critically ill patients: what is the next step? AB - Several observational studies as well as experimental data suggest that the use of macrolides is associated with better outcomes in patients with severe pneumonia. In severe community acquired pneumonia (SCAP), data demonstrate a benefit of combination therapy, including a beta-lactam plus a macrolide or floroquinolone, at least in the subgroup of patients with critical disease. Such combination seems to have a more significant impact in those with increased disease severity, particularly in those presenting with shock. In addition, data suggest that not all combinations are the same, and SCAP patients receiving combination therapy with macrolides have lower mortality than patients receiving combination with fluoroquinolones. Better results could be associated with a potential immunomodulatory effect of macrolides as well as inhibition to bacterial growth and virulence factors expression (e.g. Streptococcus pneumoniae pneumolysin). Additionally, recent studies try to incorporate these drugs to our therapeutic options in patients with other sepsis causes (e.g. nosocomial pneumonia) and pathogens (e.g. Pseudomonas aeruginosa). In this review, we will assess these issues, discussing the available evidence on macrolides use and highlighting potential research questions to be assessed on this field. PMID- 26375789 TI - Diagnostic accuracy of hemoconcentration for pulmonary edema as the cause of weaning failure. AB - BACKGROUND: Our objective was to assess the diagnostic accuracy of hemoconcentration for cardiogenic pulmonary edema (PE) as the cause of weaning failure, using left ventricular filling pressure elevation assessed by transthoracic echocardiography as the reference standard. METHODS: This prospective observational study included 41 patients who failed their first spontaneous breathing trial of weaning from mechanical ventilation. They were divided into two groups, with and without PE by echocardiographic criteria. Hemoconcentration and other hemodynamic parameters were compared between the groups. RESULTS: The group (N.=21) with PE by echocardiographic criteria had a higher frequency of failure of the second spontaneous breathing trial (P=0.03) and a longer total weaning time (P=0.02) compared to the other group. The receiver-operating characteristics curve indicated that changes in plasma protein or hemoglobin concentration from initiation to completion of the second spontaneous breathing trial did not predict PE as the cause of failure (areas under the receiver-operating characteristics curve, 0.47+/-0.09 and 0.51+/-0.09, respectively). The only factor predicting failure due to PE was a positive fluid balance from intensive care unit admission to study inclusion (P=0.01). The increase in mean arterial blood pressure seemed suggestive of weaning failure due to cardiac causes. CONCLUSIONS: Compared to echocardiographic criteria for left ventricular filling pressure elevation, hemoconcentration assessed based on plasma protein and hemoglobin levels did not help to diagnose cardiogenic PE as the cause of weaning failure. PMID- 26375790 TI - Neurally-adjusted ventilatory assist (NAVA) in children: a systematic review. AB - INTRODUCTION: Application of mechanical ventilation in spontaneously breathing children remains a challenge for several reasons: mainly, small tidal volumes and high respiratory rates, especially in the presence of leaks, interfere with patient-ventilator synchrony. Leaks also cause unreliable monitoring of respiratory drive and respiratory rate. Furthermore, ventilator adjustment must take into account that infants have strong vagal reflexes, demonstrate central apnea and periodic breathing, with a high variability in breathing pattern. Neurally-adjusted ventilatory assist (NAVA) is a mode of ventilation whereby the timing and amount of ventilatory assist is controlled by the patient's neural respiratory drive. Since NAVA uses the diaphragm electrical activity (Edi) as the controller signal, it is possible to deliver synchronized assist, both invasively and non-invasively (NIV-NAVA), to follow the variability in breathing pattern, and to monitor patient respiratory drive, independent of leaks. EVIDENCE ACQUISITION: This article provides a review of the scientific literature pertaining to the use of NAVA in children (neonatal and pediatric age groups). Both the invasive and non-invasive NAVA publications are summarized, as well as the use of Edi monitoring. EVIDENCE SYNTHESIS: Overall, the use of NAVA and Edi monitoring is feasible and safe. Compared to conventional ventilation, NAVA improves patient-ventilator interaction, and provides lower peak inspiratory pressure. CONCLUSIONS: Evidence from a few trials suggests improved comfort, less sedation, and reduced length of stay. PMID- 26375791 TI - Is there a need for a support in the surgical decision-making process? PMID- 26375792 TI - Let's spread the METhod. PMID- 26375793 TI - Hydroxyzine and QTc interval: drugs without sin cast the first stone! PMID- 26375794 TI - Etiologic Subtypes of Watershed Infarcts. AB - BACKGROUND: Two types of watershed infarcts (WI) are recognized. Internal WI are usually attributed to either severe stenosis in large arteries or acute hypotensive events, whereas external WI are thought to be caused by embolism. The aim of this study was to determine the etiologic background and prognosis of external and internal WI in our patients. METHODS: We reviewed the medical records and diffusion-weighted images of the patients who were admitted to our stroke unit with acute ischemic stroke between January 2012 and November 2014. The demographics, clinical features, radiologic investigations, and other etiologic tests of the patients with internal or external WI were recorded. We determined etiologic stroke subtypes according to the automated Causative Classification System. RESULTS: Fifty-three patients with WI were detected in our registry. Twenty-two (41.5%) of them were women. The mean age was 69 +/- 12.8 (33 98) years. Twenty-one (39.6%) patients had external WI: 7 (33.3%) of them had large-artery atherosclerosis (LAA), 8 (38.1%) patients had cardioembolism, 3 (14.3%) patients had stroke due to other causes (vasculitis; n = 3), and etiologic subtype was undetermined in 3 patients (14.3%). Thirty-two (60.4%) patients had internal WI: 21 (65.6.%) of them had LAA, 5 (15.6%) patients had cardioembolism, 3 (9.4%) patients had stroke due to other causes (aneurysm; n = 1, hypercoagulability due to chronic myeloid leukemia; n = 1, vasculitis; n = 1), and etiologic subtype of 3 (9.4%) patients remained cryptogenic. LAA was significantly associated with internal WI (P = .024). Hypertension was more common in patients with internal WI (P = .035). CONCLUSIONS: In this series, cardioembolism was the most common etiologic subtype in the patients with external WI, whereas internal WI were significantly associated with LAA. Uncommon causes should also be investigated in cryptogenic patients. PMID- 26375795 TI - Spontaneous Subarachnoid Hemorrhage with Negative Angiography Managed in a Stroke Unit: Clinical and Prognostic Characteristics. AB - BACKGROUND: Perimesencephalic subarachnoid hemorrhage (p-SAH) is linked to a benign prognosis compared with aneurysmal SAH. However, the outcome in nonperimesencephalic angiographically negative SAH (np-SAH) is not well established. We reviewed our experience and evaluated the clinical and prognostic differences between patients with p-SAH and np-SAH. METHODS: Retrospective observational study based on data collected prospectively from all patients admitted to our hospital with SAH during the past 11 years. After selecting patients with normal angiography, we categorized them as either p-SAH or np-SAH according to the Rinkel criteria. Demographic, clinical, radiologic, and prognostic features were recorded. RESULTS: We collected a total of 41 (12.53%) angiographically negative SAH: 17 p-SAH (41.46%) and 24 np-SAH (58%-53%). The np SAH group included the 6 patients with Glasgow Coma Scale (GCS) less than 15 (P = .083), and all 5 patients with Hunt & Hess (H&H) scores more than II (P = .045), being the GCS = 15 and H&H less than II in the rest of np-SAH and in all of the p SAH patients. The average hospital stay in days was longer in the np-SAH group (24 +/- 7.08) than in the p-SAH group (17 +/- 5.11; P = .55). Hydrocephalus requiring external ventricular drainage (EVD) was only recorded in the np-SAH group (29.16%, P = .029). On discharge, all patients had H&H grade less than II and modified Rankin Scale measured 3 months later was less than 2 in both groups. CONCLUSIONS: Our results agree with other studies showing a low complication rate for SAH patients with a normal angiography, especially in the p-SAH group. The prognosis appears to be less favorable in terms of a more frequent need for EVD, so a more cautious approach is recommended in this subgroup. PMID- 26375796 TI - Limited versus Whole-Brain Perfusion for the Indication of Thrombolysis in the Extended Time Window of Acute Cerebral Ischemia. AB - BACKGROUND: Perfusion computed tomography (PCT) has emerged as alternative to magnetic resonance imaging (MRI) for assessment of patients clinically qualifying for off-label thrombolysis within 4.5 to 9 hours after onset of ischemic stroke. However, disadvantage of PCT is its often limited anatomic coverage with only 2 or 3 slices when using a 4- to 64-section scanner. Our purpose was therefore to evaluate the value of 2- and 3-slice perfusion compared to whole-brain perfusion. METHODS: One hundred twenty-five patients undergoing MRI beyond 4.5 hours after symptom onset with supratentorial perfusion deficit were selected retrospectively. Accordingly to PCT slice positioning, 2 or 3 slices of the whole brain perfusion weighted imaging data set were depicted. Volumes of infarct (using cerebral blood volume) and penumbra (using time-to-peak and cerebral blood volume) were calculated, and results were compared with 2- and 3-slice-derived volumes, respectively. RESULTS: Whole-brain imaging revealed a mismatch of more than 20% in 68.8% of patients (defined as 100%). Two-slice imaging detected a perfusion deficit in 72% and a mismatch in 48.8% (sensitivity = 70.9%). Three slice imaging detected a perfusion deficit in 76% and a mismatch in 50.4% (sensitivity = 73.3%). Although there was no significant difference between 2- and 3-slice imaging (P > .23), both techniques revealed significantly less patients with mismatch compared to whole-brain coverage (P < .01). CONCLUSIONS: Two- and 3-slice imaging like obtained with PCT on most installed CT systems to assess perfusion deficits with subsequent mismatch calculation in acute stroke outside the 4.5-hour time window is significantly inferior to whole-brain coverage and, hence, has to be considered as a less-than-ideal solution. PMID- 26375797 TI - Key aspects of successful rehabilitation after repeated or serious driving offenses. AB - OBJECTIVE: In Germany, license restoration after serious or repeated offenses requires a positive medical psychological assessment (MPA), a test to determine the driver's aptitude. Fulfilling the conditions necessary for a positive MPA often takes longer than the period of license revocation, which is perhaps due to the involvement of different personal, organizational, and environmental factors. To optimize the rehabilitation process, the present study analyzed the key aspects of successful rehabilitation after repeated or serious driving offenses. METHODS: After participating in the MPA, 1,631 subjects completed a questionnaire about rehabilitation efforts. The selection of items for this questionnaire was made according to our own prior research, interviews with problem drivers, and the diagnostic criteria for the MPA. Participants were asked when and from whom they obtained certain information and how relevant this information was for their success. In contrast to other studies, which used reoffense rates as a criterion for successful rehabilitation, we used a positive MPA result (positive, negative, or training) as the criterion for success. RESULTS: Just over half (52%) of the participants considered themselves optimally informed about the rehabilitation process. The others (47.4% of participants) judged the adequacy of information received as less than satisfactory. Offenders who did not partake in counseling before the MPA achieved a successful result only about half as often (37.1%) as those who did (70%) and were around 3 times as likely to have additional courses imposed upon them (21 vs. 7.6%). Of the offenders who received crucial and helpful information at an early stage, 62.4% attained a positive MPA at the first attempt (regardless of having attended any training courses). The success rate for the first attempt rose to 81% for offenders who were well informed at an early stage and participated in counseling before their first MPA. CONCLUSION: The results clearly indicate that the provision of relevant information at an early stage combined with counseling has a beneficial influence on success rates for the rehabilitation process (an increase from 37.1 to 81%). As such, we recommend the introduction of obligatory license consultations, offered by MPA experts, involving a status assessment to customize offenders' rehabilitation and thereby provide more or less intensive guidance or coaching depending on offenders' characteristics throughout their progression through the MPA system. PMID- 26375798 TI - Gardening is beneficial for adult mental health: Scottish Health Survey, 2012 2013. AB - BACKGROUND: Gardening has been reported as being beneficial for mental well-being for vulnerable populations since 2000. However, little is known concerning its role in the general population. Therefore, the aim of the present study was to investigate the relationship of gardening and mental health in adults in a countrywide and population-based setting. METHODS: Data was retrieved from and analysed in the Scottish Health Survey, 2012-2013. Information on demographics, lifestyle factors, gardening engagement, and adult mental health by General Health Questionnaire was obtained by household interview. Statistical analyses including chi-square test, t-test and survey-weighted logistic and multi-nominal regression modelling were performed. RESULTS: Of 9709 Scottish adults aged 16-99, 5 531 (57.0%) people did not do any gardening or building work in the last four weeks. A total of 888 (9.2%) people reported poor self-rated health. Gardening was associated with adult mental health in people both with or without heart conditions including ability to concentrate, feeling playing a useful part in things, feeling capable of making decisions, thinking of self as worthless, feeling reasonably happy, etc. CONCLUSION: General adults with or without heart conditions could benefit from engaging with gardening or building work. Future public health programmes promoting such activity should be encouraged in order to optimise adult mental health. PMID- 26375800 TI - A Method of Three-Dimensional Recording of Mandibular Movement Based on Two Dimensional Image Feature Extraction. AB - BACKGROUND AND OBJECTIVE: To develop a real-time recording system based on computer binocular vision and two-dimensional image feature extraction to accurately record mandibular movement in three dimensions. METHODS: A computer based binocular vision device with two digital cameras was used in conjunction with a fixed head retention bracket to track occlusal movement. Software was developed for extracting target spatial coordinates in real time based on two dimensional image feature recognition. A plaster model of a subject's upper and lower dentition were made using conventional methods. A mandibular occlusal splint was made on the plaster model, and then the occlusal surface was removed. Temporal denture base resin was used to make a 3-cm handle extending outside the mouth connecting the anterior labial surface of the occlusal splint with a detection target with intersecting lines designed for spatial coordinate extraction. The subject's head was firmly fixed in place, and the occlusal splint was fully seated on the mandibular dentition. The subject was then asked to make various mouth movements while the mandibular movement target locus point set was recorded. Comparisons between the coordinate values and the actual values of the 30 intersections on the detection target were then analyzed using paired t-tests. RESULTS: The three-dimensional trajectory curve shapes of the mandibular movements were consistent with the respective subject movements. Mean XYZ coordinate values and paired t-test results were as follows: X axis: -0.0037 +/- 0.02953, P = 0.502; Y axis: 0.0037 +/- 0.05242, P = 0.704; and Z axis: 0.0007 +/- 0.06040, P = 0.952. The t-test result showed that the coordinate values of the 30 cross points were considered statistically no significant. (P<0.05). CONCLUSIONS: Use of a real-time recording system of three-dimensional mandibular movement based on computer binocular vision and two-dimensional image feature recognition technology produced a recording accuracy of approximately +/- 0.1 mm, and is therefore suitable for clinical application. Certainly, further research is necessary to confirm the clinical applications of the method. PMID- 26375799 TI - Glutamine contributes to maintenance of mouse embryonic stem cell self-renewal through PKC-dependent downregulation of HDAC1 and DNMT1/3a. AB - Although glutamine (Gln) is not an essential amino acid, it is considered a critical substrate in many key metabolic processes that control a variety of physiological functions and are involved in regulating early embryonic development. Thus, we investigated the effect of Gln on regulation of mouse embryonic stem cell (mESC) self-renewal and related signaling pathways. Gln deprivation decreased Oct4 expression as well as expression of cell cycle regulatory proteins. However, Gln treatment retained the expression of cell cycle regulatory proteins and the Oct4 in mESCs, which were blocked by compound 968 (a glutaminase inhibitor). In addition, Gln stimulated PI3K/Akt pathway, which subsequently elicited PKCepsilon translocation to membrane without an influx of intracellular Ca(2+). Inhibition of Akt and PKC blocked Gln-induced Oct4 expression and proliferation. Gln also stimulated mTOR phosphorylation in a time dependent manner, which abolished by PKC inhibition. Furthermore, Gln increased the cellular population of both Oct4 and bromodeoxyuridine positive cells, suggesting that Gln regulates self-renewal ability of mESCs. Gln induced a decrease in HDAC1, but not in HDAC2, which were blocked by PKC inhibitors. Gln treatment resulted in an increase in global histone acetylation and methylation. In addition, Gln significantly reduced methylation of the Oct4 promoter region through decrease in DNMT1 and DNMT3a expression, which were blocked by PKC and HDAC inhibitors. In conclusion, Gln stimulates mESC proliferation and maintains mESC undifferentiation status through transcription regulation via the Akt, PKCepsilon, and mTOR signaling pathways. PMID- 26375801 TI - Early Child Social-Emotional Problems and Child Obesity: Exploring the Protective Role of a Primary Care-Based General Parenting Intervention. AB - OBJECTIVE: To determine whether early social-emotional problems are associated with child feeding practices, maternal-child feeding styles, and child obesity at age 5 years, in the context of a primary care-based brief general parenting intervention led by an integrated behavioral health specialist to offer developmental monitoring, on-site intervention, and/or referrals. METHODS: A retrospective cohort study was conducted of mothers with 5-year-old children previously screened using the Ages and Stages Questionnaires: Social-Emotional (ASQ:SE) during the first 3 years of life. ASQ:SE scores were dichotomized "not at risk" versus "at risk." "At risk" subjects were further classified as participating or not participating in the intervention. Regression analyses were performed to determine relationships between social-emotional problems and feeding practices, feeding styles, and weight status at age 5 years based on participation, controlling for potential confounders and using "not at risk" as a reference group. RESULTS: Compared with children "not at risk," children "at risk no participation" were more likely to be obese at age 5 years (adjusted odds ratio, 3.12; 95% confidence interval, 1.03 to 9.45). Their mothers were less likely to exhibit restriction and limit setting and more likely to pressure to eat than mothers in the "not at risk" group. Children "at risk-participation" did not demonstrate differences in weight status compared with children "not at risk." CONCLUSION: Early social-emotional problems, unmitigated by intervention, were related to several feeding styles and to obesity at age 5 years. Further study is needed to understand how a general parenting intervention may be protective against obesity. PMID- 26375803 TI - Sexuality and Intellectual Disability. AB - CASE: Amad is a wonderful 16-year-old young man from Syria who has recently relocated to the United States from his war-torn native country. In his last few years in Syria, he was primarily at home with his mother, and they sought refuge with a maternal aunt in the United States seeking asylum and treatment of Amad's disability. At 8 years of age, he had intelligence testing in the United Arab Emirates, which showed a verbal intelligence score on the Wechsler intelligence scale for children (WISC) of 68 and a performance of 64. His working memory was 67 and his processing speed was 65. On arrival in the United States, his achievement was roughly at a third-grade level in Arabic. In the year and a half that he has been in the United States, he quickly improved his English skills, which he learned as a toddler. His father remains in Syria unable to safely immigrate and his mother is raising him alone in the United States with the help of her sister. They come to you for an urgent care visit because Amad recently was accused of sexual harassment by two girls at his high school. He is in a substantially separate program but is included for lunch and technology. While in the computer laboratory, he repeatedly approached the girls and asks them to "date" him, and on 1 occasion sat behind 1 girl and repeatedly reached out to stroke her long blonde hair. His mother is distraught because she recently found out that Amad also has a Facebook page and had been attempting to contact the same two girls on social media. The girls' parents recently threatened to file criminal harassment charges and Amad's mother comes to you asking for help with making Amad stop this activity. What would you do next? PMID- 26375804 TI - Primary Care Parenting Intervention and Its Effects on the Use of Physical Punishment Among Low-Income Parents of Toddlers. AB - OBJECTIVES: As part of a large randomized controlled trial, the authors assessed the impact of 2 early primary care parenting interventions-the Video Interaction Project (VIP) and Building Blocks (BB)-on the use of physical punishment among low-income parents of toddlers. They also determined whether the impact was mediated through increases in responsive parenting and decreases in maternal psychosocial risk. METHODS: Four hundred thirty-eight mother-child dyads (161 VIP, 113 BB, 164 Control) were assessed when the children were 14 and/or 24 months old. Mothers were asked about their use of physical punishment and their responsive parenting behaviors, depressive symptoms, and parenting stress. RESULTS: The VIP was associated with lower physical punishment scores at 24 months, as compared to BB and controls. In addition, fewer VIP parents reported ever using physical punishment as a disciplinary strategy. Significant indirect effects were found for both responsive parenting and maternal psychosocial risk, indicating that the VIP affects these behaviors and risk factors, and that this is an important pathway through which the VIP affects the parents' use of physical punishment. CONCLUSION: The results support the efficacy of the VIP and the role of pediatric primary care, in reducing the use of physical punishment among low-income families by enhancing parent-child relationships. In this way, the findings support the potential of the VIP to improve developmental outcomes for at-risk children. PMID- 26375805 TI - Influence of Ambient Stressors and Time Constraints on Diagnostic Accuracy of Borderline Pigmented Skin Lesions. AB - BACKGROUND: Health professionals are required to make complex decisions in dynamic contexts involving many variables and factors. Decisions are more difficult in the presence of uncertainty, urgency and high risk. OBJECTIVE: To evaluate the effect of ambient stressors and time constraints on decision making by expert dermatologists faced with borderline pigmented skin lesions (PSL) (early melanoma vs. atypical nevi). METHODS: We performed a retrospective chart review of PSL from the image databases of our department. A total of 321 PSL (219 nevi and 102 melanomas) were randomly assigned to three groups: control group, ambient stress group and time stress group. The diagnostic accuracy of each group was evaluated as sensitivity and specificity. RESULTS: Mean sensitivity and specificity of diagnosis were 69.2 and 90.5% in the control group, 62 and 81.2% in the ambient stress group and 59.6 and 82.5% in the time stress group, respectively. CONCLUSION: Time constraints and stressors negatively influenced the performance of dermatologists in the diagnosis of atypical PSL. PMID- 26375806 TI - Cancer and HIV infection in referral hospitals from four West African countries. AB - The consequences of the HIV epidemic on cancer epidemiology are sparsely documented in Africa. We aimed to estimate the association between HIV infection and selected types of cancers among patients hospitalized for cancer in four West African countries. A case-referent study was conducted in referral hospitals of Benin, Cote d'Ivoire, Nigeria and Togo. Each participating clinical ward included all adult patients seeking care with a confirmed diagnosis of cancer. All patients were systematically screened for HIV infection. HIV prevalence of AIDS defining and some non-AIDS defining cancers (Hodgkin lymphoma, leukemia, liver, lung, skin, pharynx, larynx, oral cavity and anogenital cancers) were compared to a referent group of cancers reported in the literature as not associated with HIV. Odds ratios adjusted on age, gender and lifetime number of sexual partners (aOR) and their 95% confidence intervals (CI) were estimated. Among the 1644 cancer patients enrolled, 184 (11.2%) were identified as HIV-infected. The HIV prevalence in the referent group (n=792) was 4.4% [CI 3.0-5.8]. HIV infection was associated with Kaposi sarcoma (aOR 34.6 [CI: 17.3-69.0]), non-Hodgkin lymphoma (aOR 3.6 [CI 1.9-6.8]), cervical cancer (aOR 4.3 [CI 2.2-8.3]), anogenital cancer (aOR 17.7 [CI 6.9-45.2]) and squamous cell skin carcinoma (aOR 5.2 [CI 2.0 14.4]). A strong association is now reported between HIV infection and Human Papillomavirus (HPV)-related cancers including cervical cancer and anogenital cancer. As these cancers are amenable to prevention strategies, screening of HPV related cancers among HIV-infected persons is of paramount importance in this African context. PMID- 26375807 TI - Trichotillomania and personality traits from the five-factor model. AB - OBJECTIVE: To examine whether personality traits have predictive validity for trichotillomania (TTM) diagnosis, pulling severity and control, and hair pulling style. METHODS: In study 1, logistic regression was used with TTM cases (n=54) and controls (n=25) to determine if NEO Five-Factor Inventory (NEO-FFI) personality domains predicted TTM case vs. control classification. In study 2, hierarchical multiple regression was used with TTM cases (n=164) to determine whether NEO-FFI personality domains predicted hair pulling severity and control as well as focused and automatic pulling styles. RESULTS: TTM case vs. control status was predicted by NEO-FFI neuroticism. Every 1-point increase in neuroticism scores resulted in a 10% greater chance of TTM diagnosis. Higher neuroticism, higher openness, and lower agreeableness were associated with greater pulling severity. Higher neuroticism was also associated with less control over hair pulling. Higher neuroticism and lower openness were associated with greater focused pulling. None of the personality domains predicted automatic hair pulling. CONCLUSIONS: Personality traits, especially neuroticism, can predict TTM diagnosis, hair pulling severity and control, and the focused style of pulling. None of the personality traits predicted automatic pulling. Longitudinal studies are needed to determine whether personality variables predispose to TTM onset, impact disorder course, and/or result from hair pulling behavior. PMID- 26375808 TI - Cost-utility analysis of methylphenidate treatment for children and adolescents with ADHD in Brazil. AB - OBJECTIVE: To perform a cost-utility analysis on the treatment of attention deficit hyperactivity disorder (ADHD) with methylphenidate immediate-release (MPH IR) in children and adolescents from Brazil. METHOD: A Markov model was constructed to compare MPH-IR vs. no treatment. A 24-week naturalistic study was conducted to collect transition probabilities and utility data. Effectiveness was expressed as quality-adjusted life-years (QALY), and costs reported in 2014 international dollars (I$). The perspective was the Brazilian Unified Health System as payer, and the time horizon was 6 years. RESULTS: Of 171 patients, 73 provided information at baseline, and 56 at week 24. Considering the MPH-IR monthly cost of I$ 38, the incremental cost-effectiveness ratio (ICER) of treatment was I$ 9,103/QALY for children and I$ 11,883/QALY for adolescents. In two-way sensitivity analysis, considering one Gross National Product per capita (I$ 11,530) as willingness-to-pay, a cost of no-treatment lower than I$ 45/month would render MPH-IR a cost-saving strategy. DISCUSSION: MPH-IR treatment of children and adolescents is cost-effective for ADHD patients from the Brazilian public health system perspective. Both patients and the healthcare system might benefit from such a strategy. TRIAL REGISTRATION NUMBER: NCT01705613. PMID- 26375809 TI - The American Board of Emergency Medicine Maintenance of Certification Summit. AB - BACKGROUND: The American Board of Emergency Medicine (ABEM) convened a summit of stakeholders in Emergency Medicine (EM) to critically review the ABEM Maintenance of Certification (MOC) Program. OBJECTIVE: The newly introduced American Board of Medical Specialties (ABMS) 2015 MOC Standards require that the ABMS Member Boards, including ABEM, "engage in continual quality monitoring and improvement of its Program for MOC ..." ABEM sought to have the EM community participate in the quality improvement process. DISCUSSION: A review of the ABMS philosophy of MOC and requirements for MOC were presented, followed by an exposition of the ABEM MOC Program. Roundtable discussions included strengths of the program and opportunities for improvement; defining, teaching, and assessing professionalism; identifying and filling competency gaps; and enhancing relevancy and adding value to the ABEM MOC Program. CONCLUSIONS: Several suggestions to improve the ABEM MOC Program were discussed. ABEM will consider these recommendations when developing its next revision of the ABEM MOC Program. PMID- 26375810 TI - First Rib Fracture Resulting in Horner's Syndrome. AB - BACKGROUND: First rib fractures and traumatic Horner's syndrome are both quite rare, which can make it difficult to properly diagnose the combination of these 2 conditions in the emergency department. These conditions may be associated with severe medical emergencies, such as ongoing carotid dissection. CASE REPORT: We present the case of a 33-year-old man who sustained fractures to his right second, third, and fourth ribs and a delay in the diagnosis of left Horner's syndrome after he was involved in a traffic accident. Left Horner's syndrome was caused by a left transverse fracture of the first rib. This fracture was not detected on chest radiographs and required a 3-dimensional reconstructed neck computed tomography scan for detection. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: In the diagnosis of carotid artery dissection, conventional angiography is the criterion standard but is considered invasive. CTA is less invasive, time-saving, and can show more anatomic structures in the neck in addition to the carotid arteries. It is a good screening diagnostic modality in the traumatology department. Although the treatments for Horner's syndrome and first rib fracture are conservative, the early diagnosis of both conditions can resolve the anxiety and uncertainty experienced by both doctors and patients. PMID- 26375811 TI - RKIP regulates CCL5 expression to inhibit breast cancer invasion and metastasis by controlling macrophage infiltration. AB - Accumulating evidence suggests that presence of macrophages in the tumor microenvironment add to the invasive and tumor-promoting hallmarks of cancer cells by secreting angiogenic and growth factors. RKIP is a known metastasis suppressor and interferes with several steps of metastasis. However, the mechanistic underpinnings of its function as a broad metastasis suppressor remain poorly understood. Here, we establish a novel pathway for RKIP regulation of metastasis inhibition through the negative regulation of RANTES/CCL5 thereby limiting tumor macrophage infiltration and inhibition of angiogenesis. Using a combination of loss- and gain-of- function approaches, we show that RKIP hinders breast cancer cell invasion by inhibiting expression of the CC chemokine CCL5 in vitro. We also show that the expression levels of RKIP and CCL5 are inversely correlated among clinical human breast cancer samples. Using a mouse allograft breast cancer transplantation model, we highlight that ectopic expression of RKIP significantly decreases tumor vasculature, macrophage infiltration and lung metastases. Mechanistically, we demonstrate that the inhibition of the CCL5 expression is the cause of the observed effects resulting from RKIP expression. Taken together, our results underscore the significance of RKIP as important negative regulator of tumor microenvironment. PMID- 26375812 TI - Potassium channels related to primary aldosteronism: Expression similarities and differences between human and rat adrenals. AB - Three potassium channels have been associated with primary aldosteronism (PA) in rodents and humans: KCNK3 (TASK-1), KCNK9 (TASK-3), and KCNJ5 (Kir3.4). Mice with deficiency in Kcnk3 and Kcnk9 have elevated aldosterone production and blood pressure. In humans, adrenal tumors with somatic mutations in KCNJ5 cause PA. However, there are very few reports on the expression patterns of these genes in humans versus rodents. Herein, we compared human and rat mRNA expression (by quantitative real-time polymerase chain reaction (qPCR) and protein levels (by immunohistochemistry) across three tissues (adrenal, brain, heart) and two laser captured adrenal zones (zona glomerulosa, zona fasciculata). Our findings show that expression patterns of KCNK3, KCNK9, and KCNJ5 are inconsistent between rats and humans across both tissues and adrenal zones. Thus, species variation in the expression of PA-related potassium channels indicates an evolutionary divergence in their role in regulating adrenal aldosterone production. PMID- 26375813 TI - Screening putative antigens as stimulators in the Mycobacterium bovis interferon gamma release assay for cattle. AB - Bovine tuberculosis (BTB) represents not only a significant economic concern, but also an important public health problem. Currently, interferon-gamma (IFN-gamma) release assays (IGRAs) are widely used as an adjunct to the tuberculin test (TST) for the diagnosis of BTB. A great number of international studies have demonstrated that the sensitivity of the IFN-gamma assay, which uses purified protein derivatives (PPDs) as diagnostic reagents, is superior to that of the TST. However, there are concerns about its specificity, largely because of the cross reactivity of common antigens shared by pathogenic and non-pathogenic mycobacterial species. The use of pathogen-specific antigens theoretically offers the most effective way to improve the specificity of IGRAs. In this study, we evaluated the potential utility of 13 purified recombinant putative antigens, which are highly specific to the Mycobacterium tuberculosis complex, as diagnostic reagents in IGRAs. A CFP-10-ESAT-6 fusion protein (abbreviated CE) displayed the greatest potential, whereas four region of difference 2 (RD2) antigens, especially Rv1985c were identified as potential candidate antigens, and can be included in an IGRA cocktail, together with CE as stimulators in the IFN gamma release assay for the diagnosis of BTB. PMID- 26375814 TI - Endothelial- and Platelet-Derived Microparticles Are Generated During Liver Resection in Humans. AB - BACKGROUND: Cell-derived plasma microparticles (<1.5 MUm) originating from various cell types have the potential to regulate thrombogenesis and inflammatory responses. The aim of this study was to test the hypothesis that microparticles generated during hepatic surgery co-regulate postoperative procoagulant and proinflammatory events. METHODS: In 30 patients undergoing liver resection, plasma microparticles were isolated, quantitated, and characterized as endothelial (CD31+, CD41-), platelet (CD41+), or leukocyte (CD11b+) origin by flow cytometry and their procoagulant and proinflammatory activity was measured by immunoassays. RESULTS: During liver resection, the total numbers of microparticles increased with significantly more Annexin V-positive, endothelial and platelet-derived microparticles following extended hepatectomy compared to standard and minor liver resections. After liver resection, microparticle tissue factor and procoagulant activity increased along with overall coagulation as assessed by thrombelastography. Levels of leukocyte-derived microparticles specifically increased in patients with systemic inflammation as assessed by C reactive protein but are independent of the extent of liver resection. CONCLUSIONS: Endothelial and platelet-derived microparticles are specifically elevated during liver resection, accompanied by increased procoagulant activity. Leukocyte-derived microparticles are a potential marker for systemic inflammation. Plasma microparticles may represent a specific response to surgical stress and may be an important mediator of postoperative coagulation and inflammation. PMID- 26375815 TI - Dynamic Patterns of Forces and Loading Rate in Runners with Unilateral Plantar Fasciitis: A Cross-Sectional Study. AB - AIM/HYPOTHESIS: The etiology of plantar fasciitis (PF) has been related to several risk factors, but the magnitude of the plantar load is the most commonly described factor. Although PF is the third most-common injury in runners, only two studies have investigated this factor in runners, and their results are still inconclusive regarding the injury stage. OBJECTIVE: Analyze and compare the plantar loads and vertical loading rate during running of runners in the acute stage of PF to those in the chronic stage of the injury in relation to healthy runners. METHODS: Forty-five runners with unilateral PF (30 acute and 15 chronic) and 30 healthy control runners were evaluated while running at 12 km/h for 40 meters wearing standardized running shoes and Pedar-X insoles. The contact area and time, maximum force, and force-time integral over the rearfoot, midfoot, and forefoot were recorded and the loading rate (20-80% of the first vertical peak) was calculated. Groups were compared by ANOVAs (p<0.05). RESULTS: Maximum force and force-time integral over the rearfoot and the loading rate was higher in runners with PF (acute and chronic) compared with controls (p<0.01). Runners with PF in the acute stage showed lower loading rate and maximum force over the rearfoot compared to runners in the chronic stage (p<0.01). CONCLUSION: Runners with PF showed different dynamic patterns of plantar loads during running over the rearfoot area depending on the injury stage (acute or chronic). In the acute stage of PF, runners presented lower loading rate and forces over the rearfoot, possibly due to dynamic mechanisms related to pain protection of the calcaneal area. PMID- 26375817 TI - Linkage of NCHS Population Health Surveys to Administrative Records From Social Security Administration and Centers for Medicare Medicaid Services. AB - Federally sponsored health surveys are a critical source of information on public health in the United States. The National Center for Health Statistics (NCHS) is the nation's principal health statistics agency and is responsible for collecting accurate, relevant, and timely data. NCHS conducts several population-based national surveys as well as collecting vital statistics data, which are used by a broad range of users (researchers and policy makers, among others) to evaluate and profile the health of the American people. These national health surveys provide rich cross-sectional information on risk factors such as smoking, height and weight, health status, and socioeconomic circumstances, but information on longitudinal outcomes is often missing. Demand is increasing to incorporate information from additional sources in order to enhance the availability and quality of information on exposures and outcomes. PMID- 26375816 TI - High Prevalence and Clinical Relevance of Genes Affected by Chromosomal Breaks in Colorectal Cancer. AB - BACKGROUND: Cancer is caused by somatic DNA alterations such as gene point mutations, DNA copy number aberrations (CNA) and structural variants (SVs). Genome-wide analyses of SVs in large sample series with well-documented clinical information are still scarce. Consequently, the impact of SVs on carcinogenesis and patient outcome remains poorly understood. This study aimed to perform a systematic analysis of genes that are affected by CNA-associated chromosomal breaks in colorectal cancer (CRC) and to determine the clinical relevance of recurrent breakpoint genes. METHODS: Primary CRC samples of patients with metastatic disease from CAIRO and CAIRO2 clinical trials were previously characterized by array-comparative genomic hybridization. These data were now used to determine the prevalence of CNA-associated chromosomal breaks within genes across 352 CRC samples. In addition, mutation status of the commonly affected APC, TP53, KRAS, PIK3CA, FBXW7, SMAD4, BRAF and NRAS genes was determined for 204 CRC samples by targeted massive parallel sequencing. Clinical relevance was assessed upon stratification of patients based on gene mutations and gene breakpoints that were observed in >3% of CRC cases. RESULTS: In total, 748 genes were identified that were recurrently affected by chromosomal breaks (FDR <0.1). MACROD2 was affected in 41% of CRC samples and another 169 genes showed breakpoints in >3% of cases, indicating that prevalence of gene breakpoints is comparable to the prevalence of well-known gene point mutations. Patient stratification based on gene breakpoints and point mutations revealed one CRC subtype with very poor prognosis. CONCLUSIONS: We conclude that CNA associated chromosomal breaks within genes represent a highly prevalent and clinically relevant subset of SVs in CRC. PMID- 26375819 TI - Multiple Manifold Clustering Using Curvature Constrained Path. AB - The problem of multiple surface clustering is a challenging task, particularly when the surfaces intersect. Available methods such as Isomap fail to capture the true shape of the surface near by the intersection and result in incorrect clustering. The Isomap algorithm uses shortest path between points. The main draw back of the shortest path algorithm is due to the lack of curvature constrained where causes to have a path between points on different surfaces. In this paper we tackle this problem by imposing a curvature constraint to the shortest path algorithm used in Isomap. The algorithm chooses several landmark nodes at random and then checks whether there is a curvature constrained path between each landmark node and every other node in the neighborhood graph. We build a binary feature vector for each point where each entry represents the connectivity of that point to a particular landmark. Then the binary feature vectors could be used as a input of conventional clustering algorithm such as hierarchical clustering. We apply our method to simulated and some real datasets and show, it performs comparably to the best methods such as K-manifold and spectral multi manifold clustering. PMID- 26375818 TI - Administration of a CXCL12 Analog in Endotoxemia Is Associated with Anti Inflammatory, Anti-Oxidative and Cytoprotective Effects In Vivo. AB - BACKGROUND: The chemokine receptor CXCR4 is a multifunctional receptor which is activated by its natural ligand C-X-C motif chemokine 12 (CXCL12). As CXCR4 is part of the lipopolysaccharide sensing complex and CXCL12 analogs are not well characterized in inflammation, we aimed to uncover the systemic effects of a CXCL12 analog in severe systemic inflammation and to evaluate its impact on endotoxin induced organ damages by using a sublethal LPS dose. METHODS: The plasma stable CXCL12 analog CTCE-0214D was synthesized and administered subcutaneously shortly before LPS treatment. After 24 hours, mice were sacrificed and blood was obtained for TNF alpha, IFN gamma and blood glucose evaluation. Oxidative stress in the liver and spleen was assessed and liver biotransformation capacity was determined. Finally, CXCR4, CXCL12 and TLR4 expression patterns in liver, spleen and thymus tissue as well as the presence of different markers for apoptosis and oxidative stress were determined by means of immunohistochemistry. RESULTS: CTCE-0214D distinctly reduced the LPS mediated effects on TNF alpha, IFN gamma, ALAT and blood glucose levels. It attenuated oxidative stress in the liver and spleen tissue and enhanced liver biotransformation capacity unambiguously. Furthermore, in all three organs investigated, CTCE-0214D diminished the LPS induced expression of CXCR4, CXCL12, TLR4, NF-kappaB, cleaved caspase-3 and gp91 phox, whereas heme oxygenase 1 expression and activity was induced above average. Additionally, TUNEL staining revealed anti-apoptotic effects of CTCE-0214D. CONCLUSIONS: In summary, CTCE-0214D displayed anti-inflammatory, anti-oxidative and cytoprotective features. It attenuated reactive oxygen species, induced heme oxygenase 1 activity and mitigated apoptosis. Thus, the CXCR4/CXCL12 axis seems to be a promising target in the treatment of acute systemic inflammation, especially when accompanied by a hepatic dysfunction and an excessive production of free radicals. PMID- 26375820 TI - Correction: Trophic Ecology of Atlantic Bluefin Tuna (Thunnusthynnus) Larvae from the Gulf of Mexico and NW Mediterranean Spawning Grounds: A Comparative Stable Isotope Study. PMID- 26375821 TI - Development of bingeing in rats altered by a small operant requirement. AB - Previous studies have shown that providing an optional food for a brief period of time to non-food deprived rats on an intermittent basis in the home cage engenders significantly more intake (binge-type behavior) than when the optional food is provided for a brief period on a daily basis. Experiment 1 examined the effects of placing a small operant response requirement on access to an optional food (vegetable shortening) on the establishment of binge-type behavior. Experiment 2 examined the effects of different schedules of reinforcement, a period of abstinence from shortening, and 24h of food deprivation on established binge-type behavior. In Experiment 1 the group of rats with 30-min access to shortening on an intermittent basis in their home cages (IC) consumed significantly more shortening than the group with 30-min daily access in the home cage (DC). The group with 30-min intermittent access in an operant chamber (IO group) earned significantly more reinforcers than the group with 30-min daily access in an operant chamber (DO). In Experiment 2, the IO group earned significantly more reinforcers than the DO group regardless of the response cost, the period of shortening abstinence, and overnight food deprivation. These results demonstrate that while intermittent access generates binge-type eating, the size of the binge (intake) can be altered by different contingency arrangements. PMID- 26375822 TI - Low-Frequency IL23R Coding Variant Associated with Crohn's Disease Susceptibility in Japanese Subjects Identified by Personal Genomics Analysis. AB - BACKGROUND: The common disease-common variant hypothesis is insufficient to explain the complexities of Crohn's disease (CD) genetics; therefore, rare variants are expected to be important in the disease. We explored rare variants associated with susceptibility to CD in Japanese individuals by personal genomic analysis. METHODS: Two-step analyses were performed. The first step was a trio analysis with whole-exome sequence (WES) analysis and the second was a follow-up case-control association study. The WES analysis pipeline comprised Burrows Wheeler Aligner, Picard, Genome Analysis Toolkit, and SAMTOOLS. Single nucleotide variants (SNVs)/indels were annotated and filtered by using programs implemented in ANNOVAR in combination with identity-by-descent (IBD), subsequently were subjected to the linkage based, and de novo based strategies. Finally, we conducted an association study that included 176 unrelated subjects with CD and 358 healthy control subjects. RESULTS: In family members, 234,067-297,523 SNVs/indels were detected and they were educed to 106-146 by annotation based filtering. Fifty-four CD variants common to both individuals of the affected sib pair were identified. The linkage based strategy detected five candidate variants whereas the de novo based strategy identified no variants. Consequently, five candidates were analyzed in the case-control association study. CD showed a significant association with one variant in exon 4 of IL23R, G149R [rs76418789, P = 3.9E-5, odds ratio (OR) 0.21, 95% confidence interval (CI) 0.09-0.47 for the dominant model (AA + AG versus GG), and P = 7.3E-5, OR 0.21, 95% CI 0.10-0.48 for AG versus GG, and P = 7.2E-5, OR 0.23, 95% CI 0.10-0.50 for the allele model]. CONCLUSIONS: The present study, using personal genomics analysis of a small CD pedigree, is the first to show that the low-frequency non-synonymous variant of IL23R, rs76418789, protects against CD development in Japanese subjects. PMID- 26375823 TI - Blastocystis sp. in Irritable Bowel Syndrome (IBS)--Detection in Stool Aspirates during Colonoscopy. AB - Blastocystis is one of the most common gut parasites found in the intestinal tract of humans and animals. Its' association with IBS is controversial, possibly as a result of irregular shedding of parasites in stool and variation in stool detection. We aimed to screen for Blastocystis in colonic stool aspirate samples in adult patients with and without IBS undergoing colonoscopy for various indications and measure the interleukin levels (IL-8, IL-3 and IL-5). In addition to standard stool culture techniques, polymerase chain reaction (PCR) techniques were employed to detect and subtype Blastocystis. All the serum samples collected were subjected for ELISA studies to measure the interleukin levels (IL-8, IL-3 and IL-5). Among 109 (IBS n = 35 and non-IBS n = 74) adults, direct stool examination and culture of colonic aspirates were initially negative for Blastocystis. However, PCR analysis detected Blastocystis in 6 (17%) IBS and 4 (5.5%) non-IBS patients. In the six positive IBS patients by PCR method, subtype 3 was shown to be the most predominant (3/6: 50%) followed by subtype 4 (2/6; 33.3%) and subtype 5 (1/6; 16.6%). IL-8 levels were significantly elevated in the IBS Blasto group and IBS group (p<0.05) compared to non-IBS and non-IBS Blasto group. The level of IL-3 in were seen to be significantly higher in than IBS Blasto group and IBS group (p<0.05) compared to non-IBS. Meanwhile, the IL-5 levels were significantly higher in IBS Blasto group (p<0.05) compared to non-IBS and non-IBS Blasto group. This study implicates that detecting Blastosystis by PCR method using colonic aspirate samples during colonoscopy, suggests that this may be a better method for sample collection due to the parasite's irregular shedding in Blastocystis-infected stools. Patients with IBS infected with parasite showed an increase in the interleukin levels demonstrate that Blastocystis does have an effect in the immune system. PMID- 26375826 TI - Correction to Anestis et al. (2014). PMID- 26375824 TI - Psychiatric Comorbidity Is Associated Prospectively with Diminished Opioid Analgesia and Increased Opioid Misuse in Patients with Chronic Low Back Pain. AB - BACKGROUND: Opioids are frequently prescribed for chronic low back pain (CLBP), but there are little prospective data on which patient subgroups may benefit. Psychiatric comorbidity, such as high levels of depression and anxiety symptoms (termed comorbid negative affect [NA]), is a common presentation and may predict diminished opioid analgesia and/or increased opioid misuse. METHODS: The authors conducted a 61/2-month prospective cohort study of oral opioid therapy, with an active drug/placebo run-in period, in 81 CLBP patients with low, moderate, and high levels of NA. Treatment included an opioid titration phase with a prescribing physician blinded to NA group assignment and a 4-month continuation phase, during which subjects recorded daily pain levels using an electronic diary. The primary outcome was the percent improvement in average daily pain, summarized weekly. RESULTS: There was an overall 25% dropout rate. Despite the high NA group being prescribed a higher average daily dose of morphine equivalents, linear mixed model analysis revealed that the 24 study completers in each of the high NA and low NA groups had an average 21 versus 39% improvement in pain, respectively (P < 0.01). The high NA group also had a significantly greater rate of opioid misuse (39 vs. 8%, P < 0.05) and significantly more and intense opioid side effects (P < 0.01). CONCLUSIONS: These results indicate that the benefit and risk considerations in CLBP patients with high NA versus low NA are distinctly different. Thus, NA is an important phenotypic variable to characterize at baseline, before deciding whether to prescribe opioids for CLBP. PMID- 26375825 TI - A Noninvasive Method for Nanoscale Electrostatic Gating of Pristine Materials. AB - Electrostatic gating is essential for defining and control of semiconducting devices. However, nanofabrication processes required for depositing gates inevitably degrade the pristine quality of the material of interest. Examples of materials that suffer from such degradation include ultrahigh mobility GaAs/AlGaAs two-dimensional electron gases (2DEGs), graphene, topological insulators, and nanowires. To preserve the pristine material properties, we have developed a flip-chip setup where gates are separated from the material by a vacuum, which allows nanoscale electrostatic gating of the material without exposing it to invasive nanoprocessing. An additional benefit is the vacuum between gates and material, which, unlike gate dielectrics, is free from charge traps. We demonstrate the operation and feasibility of the flip-chip setup by achieving quantum interference at integer quantum Hall states in a Fabry-Perot interferometer based on a GaAs/AlGaAs 2DEG. Our results pave the way for the study of exotic phenomena including fragile fractional quantum Hall states by preserving the high quality of the material. PMID- 26375827 TI - The impact of autism spectrum disorder and alexithymia on judgments of moral acceptability. AB - One's own emotional response toward a hypothetical action can influence judgments of its moral acceptability. Some individuals with autism spectrum disorder (ASD) exhibit atypical emotional processing, and moral judgments. Research suggests, however, that emotional deficits in ASD are due to co-occurring alexithymia, meaning atypical moral judgments in ASD may be due to alexithymia also. Individuals with and without ASD (matched for alexithymia) judged the moral acceptability of emotion-evoking statements and identified the emotion evoked. Moral acceptability judgments were predicted by alexithymia. Crucially, however, this relationship held only for individuals without ASD. While ASD diagnostic status did not directly predict either judgment, those with ASD did not base their moral acceptability judgments on emotional information. Findings are consistent with evidence demonstrating that decision-making is less subject to emotional biases in those with ASD. PMID- 26375831 TI - Pain, Pain, Go Away! Evidence-Based Review of Developmentally Appropriate Pain Assessment for Children in a Postoperative Setting. AB - Assessment and management of pain in children with orthopaedic injuries can be difficult, especially in the postoperative period. Factors such as developmental stage of the child, medications used intraoperatively and postoperatively, patient anxiety, and perceptions of family members and nurses caring for the patient can affect the accuracy of pain assessment in this population. The purposes of this article were to provide an overview of developmentally appropriate pain assessment tools, to describe factors that can affect the perception of pain, and to perform a pain assessment postoperatively in the pediatric orthopaedic patient. PMID- 26375828 TI - Codevelopment of psychopathic features and alcohol use during emerging adulthood: Disaggregating between- and within-person change. AB - The current study examined whether there is a bidirectional association between changes in alcohol use and psychopathic features during the transition into emerging adulthood. The nature of this association was investigated among a large sample of serious male adolescent offenders (N = 1,170) across 7 annual assessments (ages ~17-23), with a focus on disaggregating between- and within person change. Findings indicated that there was significant variability between participants in their rate of change of psychopathic features and alcohol use throughout this period of development. Both, between- and within-person increases in alcohol use tended to parallel increases in psychopathic features during the transition into emerging adulthood. In addition, evidence indicated that during years when adolescents consumed more alcohol than normal, they experienced higher than usual levels of self-reported psychopathic features at the subsequent assessment. The relevance of these findings for public policy and their potential to inform treatments and interventions are discussed. PMID- 26375833 TI - A 52-Year-Old Man With a Tuft Fracture and Hand Cellulitis. AB - A 52-year-old man presented to the emergency department (ED) 1 week after getting his right index finger shut in a car door. The patient complained of right index finger pain. His entire hand was edematous and reddened. After evaluation in the ED and x-ray, the patient was diagnosed with a tuft fracture, right index finger/hand cellulitis, and possible osteomyelitis. The patient received tetanus diphtheria i.m., vancomycin 1 g i.v., and ceftriaxone (Rocephin) 2 g i.v. while in the ED and was admitted with referral to a hand specialist. The patient was discharged after 10 days of parental antibiotics. He has a history of sarcoidosis, hypertension, diabetes mellitus, and scleroderma. He is currently not taking any medications and denies allergies to medications and latex. The patient had no significant somatic findings. He was afebrile. PMID- 26375835 TI - Assessment of the Patient-Centered and Family-Centered Care Experience of Total Joint Replacement Patients Using a Shadowing Technique. AB - In 2030, when baby boomers reach 65 years of age and represent 18% of the population, it is anticipated that 67 million adults will have a diagnosis of arthritis increasing the demand for total hip and knee arthroplasty. With the growing emphasis on patient- and family-centered care, the aim of this project was to assess the patient experience of patients and families throughout the entire spectrum of the total joint replacement service line care at a university regional trauma hospital. A shadowing methodology as defined by the Institute for Health Improvement was utilized. Eight patient/family groups undergoing total joint replacements were shadowed. The mapped care experience included time, caregiver, activity, shadower observations, and impressions. Findings revealed inconsistencies in the delivery of patient- and family-centered care. Communication and interactions were predominantly provider-centric, with a focus on care routines versus the patient and family, and anticipation that care would be medically directed. PMID- 26375837 TI - The Problems Experienced by Parents Providing Postoperative Home Care Following Their Child's Surgery for Developmental Dysplasia of the Hip. AB - BACKGROUND: Families, especially mothers, experience problems providing home care after their child's surgery for developmental dysplasia of the hip (DDH). PURPOSE: To assess the problems experienced by parents providing postoperative home care to their child after DDH surgery. METHODS: This was a descriptive cross sectional study. The sample consisted of 33 parents. Data were collected through a survey conducted at the hospital following the child's surgery and by telephone 4-6 weeks after surgery. Frequencies, means, percentages, and chi-square tests were used to analyze the data. RESULTS: The parents (93.9% women) provided postoperative care for approximately 3 months. Nearly all of the parents (97%) had physical (96.9%), psychological (65.6%), and social (75.0%) problems in addition to child care problems. CONCLUSIONS: We recommend preparing a comprehensive discharge-training package for parents after their child's DDH surgery, supplementing home care instructions with visual training materials, and providing telephone counseling to parents after discharge. PMID- 26375839 TI - A Pilot Study to Identify Modifiable and Nonmodifiable Variables Associated With Osteopenia and Osteoporosis in Men. AB - Osteoporosis is typically associated with women, but men can also be affected. Less is known about the factors influencing the development of osteoporosis in the male population. This pilot study attempted to identify variables associated with osteopenia or osteoporosis in men. The 101 male participants completed a questionnaire that examined modifiable and nonmodifiable variables: alcohol consumption, smoking, exercise history, fracture history as an adult, and family history of osteoporosis. Objective variables collected included age, height, and weight to calculate body mass index. Bone mineral density was calculated using dual-energy x-ray absorptiometry. Osteopenia or osteoporosis was identified in 62 of the male participants. Consumption of alcohol and cigarettes with higher body mass index was correlated with greater likelihood of osteopenia and osteoporosis. PMID- 26375841 TI - The Effect of Multifactorial Intervention Programs on Health Behavior and Symptom Control Among Community-Dwelling Overweight Older Adults With Knee Osteoarthritis. AB - BACKGROUND: Osteoarthritis of the knee (OA knee), especially in older adults, is the most common chronic illness and a major public health problem. Overweight older adults are at a high risk of developing OA knee and suffering from OA knee symptoms, which cause older adults to become disabled and have functional limitations. The reduction of knee pain and the maintenance of physical functions of overweight older adults with OA knee are critical. PURPOSE: To examine the effect of multifactorial intervention programs (MUFIPs) on health behavior and symptoms control in overweight older Thais with knee osteoarthritis. METHODS: Eighty overweight older Thais with knee osteoarthritis living in communities were randomly assigned into experimental and control groups. The experimental group received MUFIPs, including health education, a weight-reduction/control program, a quadriceps exercise training class followed by a home-based exercise program, and a home visit program. The control group did not receive the MUFIPs. Changes in the study variables were assessed at baseline and 8- week follow-ups. Data were analyzed by using descriptive and independent t test analyses. RESULTS: The experimental group had significant improvement in osteoarthritis knowledge, illness representation, health behavior, movement ability, and joint range of motion, and had reduction in knee pain and body weight. All these variables were observed to have significant differences between experimental and control groups. CONCLUSION: The MUFIPs can break down the progression of the disease among overweight older Thais with knee osteoarthritis. PMID- 26375843 TI - The Advantages of Competencies. PMID- 26375846 TI - A Trade-off Between Invasiveness and Efficacy: Ureteroscopy vs Shock Wave Lithotripsy: Commentary on: Comparative effectiveness of shock wave lithotripsy and ureteroscopy for treating patients with kidney stones. PMID- 26375845 TI - Phase II Trial of Carboplatin, Everolimus, and Prednisone in Metastatic Castration-resistant Prostate Cancer Pretreated With Docetaxel Chemotherapy: A Prostate Cancer Clinical Trial Consortium Study. AB - OBJECTIVE: To conduct a phase II trial of the combination of carboplatin, prednisone, and everolimus in metastatic castrate-resistant prostate cancer (mCRPC) as mTOR inhibition can overcome resistance to chemotherapy in prostate cancer. METHODS: Patients with progressive mCRPC pretreated with docetaxel-based regimen were eligible. Performance status of 0-1 and adequate bone marrow, renal, and liver function were required. Primary end point was time to progression. Treatment consisted of carboplatin (starting dose equal to area under the curve (AUC of 5) intravenously every 21 days along with oral everolimus 5 mg once daily and prednisone 5 mg twice daily. RESULTS: Twenty-six patients were enrolled with median age of 69 years with 8 patients of African American origin. Grade 3 or 4 thrombocytopenia or neutropenia in 4 of 6 initial patients required dose adjustment of carboplatin to AUC of 4 for subsequent patients. There were no pharmacokinetic interactions between carboplatin and everolimus. The median time to progression was 2.5 months (90% confidence interval [CI], 1.8-4.3 months), and median overall survival was 12.5 months (90% CI, 7.7-18.7 months). Of 10 patients, 8 that demonstrated positive nuclear phosphorylated AKT (pAKT) staining on immunohistochemistry progressed within 9 weeks, whereas 2 patients with negative staining continued without progression for prolonged durations of 30 and 48 weeks. TSC1 gene mutations did not correlate with clinical outcome. CONCLUSION: The addition of the mTOR inhibitor everolimus to carboplatin demonstrated minimal clinical efficacy in metastatic prostate cancer. pAKT testing warrants further evaluation as a predictive marker of response to everolimus therapy. PMID- 26375847 TI - Changes in Prolapse and Urinary Symptoms After Successful Fitting of a Ring Pessary With Support in Women With Advanced Pelvic Organ Prolapse: A Prospective Study. AB - OBJECTIVE: To estimate the percentage of improvement in prolapse and urinary symptoms and adverse effects in women with advanced pelvic organ prolapse (POP) after 3 months of use of a ring pessary with support. MATERIALS AND METHODS: In this prospective study, 109 consecutive women with advanced POP were fitted with a ring pessary with support; 73 (73/109, 67.0%) of the women had a successful 3 month pessary fitting trial. Prolapse symptoms, urinary symptoms, and urinary flow parameters were assessed at baseline and at 3 months. Adverse effects were assessed within 3 months. McNemar's test and paired-sample t tests were performed. RESULTS: Prolapse and urinary symptoms improved from baseline to 3 months, including bulging (90.4% to 23.3%; P <.001) and pressure (64.4% to 13.7%; P <.001). Voiding difficulty improved in 97.8% of the women (45/46; P <.001), splinting improved in 100% (19/19; P <.001), urge urinary incontinence improved in 76.9% (30/39; P <.001), and stress urinary incontinence improved in 58.1% (18/31; P = .025) after 3 months. After pessary treatment, the differences in maximum flow rate, mean flow rate, void volume, and postvoid residual at baseline and 3 months were statistically significant (P <.05). Vaginal discharge (32/73, 43.8%) was the most common adverse event. Vaginal ulcers developed in 7 (7/73, 9.6%) of the women. CONCLUSION: The ring pessary with support was successfully fitted in patients with advanced POP with a high success rate and few complications. The pessary could resolve more than half of the prolapse and urinary symptoms. Therefore, initial conservative treatment with a ring pessary with support in advanced POP is worthwhile. PMID- 26375848 TI - Use of Medical Therapy and Success of Laser Surgery and Transurethral Resection of the Prostate for Benign Prostatic Hyperplasia. AB - OBJECTIVE: To assess the impact of surgery for benign prostatic hyperplasia (BPH) on use of medication (5-alpha reductase inhibitors, alpha blockers, antispasmodics), we assessed preoperative and postoperative medication utilization among surgically treated men. PATIENTS AND METHODS: Using the Truven Health Analytics MarketScan Commercial Claims Database, we defined a cohort of men aged <65 years who had surgical therapy for BPH with either transurethral resection of the prostate (TURP) or laser procedures from 2007 through 2009. Primary outcomes included freedom from medical or surgical intervention by 4 months after surgery (chi-square and multivariable logistic regression) and subsequent use of medical or surgical intervention in initial responders (Kaplan Meier and multivariable Cox regression). RESULTS: We identified 6430 patients treated with either TURP (3096) or laser procedure (3334) for BPH. Presurgical antispasmodic use was associated with the highest risk of medication use at 4 months after surgery (odds ratio, 5.19; 95% confidence interval (CI), 3.16-8.53 vs no medication use before surgery). At 3 years after surgery, 6% (95% CI, 4% 8%) of laser-treated and 4% (95% CI, 2%-5%) of TURP-treated patients had repeat surgical intervention, and both laser- and TURP-treated patients had an estimated new use of medication rate of 22% (95% CI, 18%-25% laser and 20%-25% TURP). The strongest predictor of intervention after surgery was preoperative antispasmodic use (hazard ratio, 2.49; 95% CI, 1.41-4.43). CONCLUSION: Our results show a need for effective patient counseling about continued or new use of medical therapy after laser and TURP procedures. However, most patients experience durable improvement after surgical intervention for BPH. PMID- 26375849 TI - Cloacal Exstrophy: A History of Gender Reassignment. PMID- 26375850 TI - The Use of DNA Barcoding in Identification and Conservation of Rosewood (Dalbergia spp.). AB - The genus Dalbergia contains many valuable timber species threatened by illegal logging and deforestation, but knowledge on distributions and threats is often limited and accurate species identification difficult. The aim of this study was to apply DNA barcoding methods to support conservation efforts of Dalbergia species in Indochina. We used the recommended rbcL, matK and ITS barcoding markers on 95 samples covering 31 species of Dalbergia, and tested their discrimination ability with both traditional distance-based as well as different model-based machine learning methods. We specifically tested whether the markers could be used to solve taxonomic confusion concerning the timber species Dalbergia oliveri, and to identify the CITES-listed Dalbergia cochinchinensis. We also applied the barcoding markers to 14 samples of unknown identity. In general, we found that the barcoding markers discriminated among Dalbergia species with high accuracy. We found that ITS yielded the single highest discrimination rate (100%), but due to difficulties in obtaining high-quality sequences from degraded material, the better overall choice for Dalbergia seems to be the standard rbcL+matK barcode, as this yielded discrimination rates close to 90% and amplified well. The distance-based method TaxonDNA showed the highest identification rates overall, although a more complete specimen sampling is needed to conclude on the best analytic method. We found strong support for a monophyletic Dalbergia oliveri and encourage that this name is used consistently in Indochina. The CITES-listed Dalbergia cochinchinensis was successfully identified, and a species-specific assay can be developed from the data generated in this study for the identification of illegally traded timber. We suggest that the use of DNA barcoding is integrated into the work flow during floristic studies and at national herbaria in the region, as this could significantly increase the number of identified specimens and improve knowledge about species distributions. PMID- 26375852 TI - Rubemamine and Rubescenamine, Two Naturally Occurring N-Cinnamoyl Phenethylamines with Umami-Taste-Modulating Properties. AB - Sensory screening of a series of naturally occurring N-cinnamoyl derivatives of substituted phenethylamines revealed that rubemamine (9, from Chenopodium album) and rubescenamine (10, from Zanthoxylum rubsecens) elicit strong intrinsic umami taste in water at 50 and 10 ppm, respectively. Sensory tests in glutamate- and nucleotide-containing bases showed that the compounds influence the whole flavor profile of savory formulations. Both rubemamine (9) and rubescenamine (10) at 10 100 ppm dose-dependently positively modulated the umami taste of MSG (0.17-0.22%) up to threefold. Among the investigated amides, only rubemamine (9) and rubescenamine (10) are able to directly activate the TAS1R1-TAS1R3 umami taste receptor. Moreover, both compounds also synergistically modulated the activation of TAS1R1-TAS1R3 by MSG. Most remarkably, rubemamine (9) was able to further positively modulate the IMP-enhanced TAS1R1-TAS1R3 response to MSG ~ 1.8-fold. Finally, armatamide (11), zanthosinamide (13), and dioxamine (14), which lack intrinsic umami taste in vivo and direct receptor response in vitro, also positively modulated receptor activation by MSG about twofold and the IMP enhanced MSG-induced TAS1R1-TAS1R3 responses approximately by 50%. In sensory experiments, dioxamine (14) at 25 ppm in combination with 0.17% MSG exhibited a sensory equivalent to 0.37% MSG. PMID- 26375853 TI - Bundling Our Health Care Future. PMID- 26375851 TI - Comprehensive Analysis of the Naturally Processed Peptide Repertoire: Differences between HLA-A and B in the Immunopeptidome. AB - The cytotoxic T cell (CTL) response is determined by the peptide repertoire presented by the HLA class I molecules of an individual. We performed an in-depth analysis of the peptide repertoire presented by a broad panel of common HLA class I molecules on four B lymphoblastoid cell-lines (BLCL). Peptide elution and mass spectrometry analysis were utilised to investigate the number and abundance of self-peptides. Altogether, 7897 unique self-peptides, derived of 4344 proteins, were eluted. After viral infection, the number of unique self-peptides eluted significantly decreased compared to uninfected cells, paralleled by a decrease in the number of source proteins. In the overall dataset, the total number of unique self-peptides eluted from HLA-B molecules was larger than from HLA-A molecules, and they were derived from a larger number of source proteins. These results in B cells suggest that HLA-B molecules possibly present a more diverse repertoire compared to their HLA-A counterparts, which may contribute to their immunodominance. This study provides a unique data set giving new insights into the complex system of antigen presentation for a broad panel of HLA molecules, many of which were never studied this extensively before. PMID- 26375855 TI - Evaluation of a Rural-Based Community Aged Intensive Recovery Program for Older Adults With Severe Mental Illness. AB - Community Aged Intensive Recovery (CAIR) programs are an integral part of Aged Persons Mental Health Services (APMHS); however, no study has investigated whether a rural-based intensive program benefits older clients with severe mental illness. The current sample comprised 119 older adults who were being managed by a CAIR program from July 2011 to June 2013. Three key results were found: (a) approximately three quarters of clients admitted to the CAIR program remained treated in the community; (b) the program assisted in significantly reducing the level of psychiatric symptom severity from CAIR entry to CAIR exit; and (c) the APMHS team with the CAIR program had a lower psychiatric inpatient rate compared to the APMHS team without the program. The current study highlights the importance of delivering effective rural-based CAIR programs to older adults experiencing severe mental illness. PMID- 26375854 TI - Saxagliptin reduces renal tubulointerstitial inflammation, hypertrophy and fibrosis in diabetes. AB - AIM: In addition to lowering blood glucose in patients with type 2 diabetes mellitus, dipeptidyl peptidase 4 (DPP4) inhibitors have been shown to be antifibrotic and anti-inflammatory. We have previously shown that DPP4 inhibition in human kidney proximal tubular cells exposed to high glucose reduced fibrotic and inflammatory markers. Hence, we wanted to demonstrate renoprotection in an in vivo model. METHODS: We used a type 1 diabetic animal model to explore the renoprotective potential of saxagliptin independent of glucose lowering. We induced diabetes in enos -/- mice using streptozotocin and matched glucose levels using insulin. Diabetic mice were treated with saxagliptin and outcomes compared with untreated diabetic mice. RESULTS: We provide novel data that saxagliptin limits renal hypertrophy, transforming growth factor beta-related fibrosis and NF kappaBp65-mediated macrophage infiltration. Overall, there was a reduction in histological markers of tubulointerstitial fibrosis. There was no reduction in albuminuria or glomerulosclerosis. CONCLUSION: Our findings highlight the potential of DPP4 inhibition as additional therapy in addressing the multiple pathways to achieve renoprotection in diabetic nephropathy. PMID- 26375856 TI - Millennial Students' Preferred Methods for Learning Concepts in Psychiatric Nursing. AB - The current longitudinal, descriptive, and correlational study explored which traditional teaching strategies can engage Millennial students and adequately prepare them for the ultimate test of nursing competence: the National Council Licensure Examination. The study comprised a convenience sample of 40 baccalaureate nursing students enrolled in a psychiatric nursing course. The students were exposed to a variety of traditional (e.g., PowerPoint((r))-guided lectures) and nontraditional (e.g., concept maps, group activities) teaching and learning strategies, and rated their effectiveness. The students' scores on the final examination demonstrated that student learning outcomes met or exceeded national benchmarks. PMID- 26375857 TI - Clinical Research Abstracts of the British Equine Veterinary Association Congress 2015. AB - REASONS FOR PERFORMING STUDY: Bronchopneumonia caused by Rhodococcus equi is an important disease of young horses throughout the world. Although early diagnosis and treatment improves the prognosis, this also increases the amount of antimicrobial usage and therefore increases the likelihood of resistance developing. OBJECTIVES: The aim of this study was to determine the level of resistance to commonly prescribed antimicrobial agents of 97 virulent Rhodococcus equi isolates. STUDY DESIGN: Analysis of archived samples. METHODS: Virulent Rhodococcus equi isolates were collected between 1991 and 2014 from clinically affected horses and from air samples collected in the breathing zone of foals. Antimicrobial susceptibility of these isolates was assessed using a disc diffusion assay with a panel of agents. The minimum inhibitory concentration (MIC) was determined for rifampicin, erythromycin, tetracycline, and neomycin using a novel resazurin-based microtitre assay. RESULTS: Resistance to rifampicin was detected in 3 of the isolates (2 collected in 2013 and one in 2014) by both methods. The MIC for these isolates was 64 MUg/ml (n = 2) and 16 MUg/ml (n = 1). All isolates collected prior to 2013 had MICs<0.125 MUg/ml, which was the limit of detection in this assay. Although no isolates were resistant to tetracycline, there was a general increase in MIC in isolates collected in recent years. No isolates were resistant to either neomycin or erythromycin, with MIC values ranging between 0.25 and 2 MUg/ml for neomycin and 0.125-1 MUg/ml for erythromycin. CONCLUSIONS: The success of the macrolide-rifampicin combination relies on the synergistic action of these 2 agents. Resistance to rifampicin will reduce the therapeutic efficacy of this treatment. It is of serious concern that the resistant isolates were all recently collected. Hopefully, recent research will lead to fewer asymptomatic foals receiving antimicrobials which will in turn reduce the likelihood of ongoing development of resistance. Ethical animal research: All organisms in this study were received by the laboratory from diagnostic accessions. Sources of funding: Funding for the study was provided by Rural Industries Research and Development Corporation and the University of Melbourne. G. Herbert was the recipient of a RN McCarthy scholarship from the Faculty of Veterinary Science. Competing interests: None declared. PMID- 26375859 TI - Electronic Tuning of 2D MoS2 through Surface Functionalization. AB - The electronic properties of thiol-functionalized 2D MoS2 nanosheets are investigated. Shifts in the valence and conduction bands and Fermi levels are observed while bandgaps remain unaffected. These findings allow the tuning of energy barriers between 2D MoS2 and other materials, which can lead to improved control over 2D MoS2 -based electronic and optical devices and catalysts. PMID- 26375858 TI - Impact of risk factors on cardiovascular risk: a perspective on risk estimation in a Swiss population. AB - INTRODUCTION: In models and scores for estimating cardiovascular risk (CVR), the relative weightings given to blood pressure measurements (BPMs), and biometric and laboratory variables are such that even large differences in blood pressure lead to rather low differences in the resulting total risk when compared with other concurrent risk factors. We evaluated this phenomenon based on the PROCAM score, using BPMs made by volunteer subjects at home (HBPMs) and automated ambulatory BPMs (ABPMs) carried out in the same subjects. METHODS: A total of 153 volunteers provided the data needed to estimate their CVR by means of the PROCAM formula. Differences (deltaCVR) between the risk estimated by entering the ABPM and that estimated with the HBPM were compared with the differences (deltaBPM) between the ABPM and the corresponding HBPM. In addition to the median values (= second quartile), the first and third quartiles of blood pressure profiles were also considered. PROCAM risk values were converted to European Society of Cardiology (ESC) risk values and all participants were assigned to the risk groups low, medium and high. RESULTS: Based on the PROCAM score, 132 participants had a low risk for suffering myocardial infarction, 16 a medium risk and 5 a high risk. The calculated ESC scores classified 125 participants into the low-risk group, 26 into the medium- and 2 into the high-risk group for death from a cardiovascular event. Mean ABPM tended to be higher than mean HBPM. Use of mean systolic ABPM or HBPM in the PROCAM formula had no major impact on the risk level. CONCLUSIONS: Our observations are in agreement with the rather low weighting of blood pressure as risk determinant in the PROCAM score. BPMs assessed with different methods had relatively little impact on estimation of cardiovascular risk in the given context of other important determinants. The risk calculations in our unselected population reflect the given classification of Switzerland as a so-called cardiovascular "low risk country". PMID- 26375860 TI - Clinical Research Abstracts of the British Equine Veterinary Association Congress 2015. AB - REASONS FOR PERFORMING STUDY: Colic remains a life-threatening condition in the horse. Ischaemia and reperfusion following correction of small intestinal strangulation may produce oxidative stress. The ability to withstand oxidative stress depends on antioxidant levels and may be linked to horse survival. OBJECTIVES: To measure peripheral antioxidant levels in horses undergoing exploratory laparotomy with small intestinal strangulation. STUDY DESIGN: Case control study. METHODS: Blood and plasma were collected from horses undergoing exploratory laparotomy for small intestinal strangulation and stored at -80 degrees C. Controls involved non-colic horses. Total plasma glutathione was measured spectrophotometrically at 412 nm using the 5,5'-dithiobis-(2 nitrobenzoic acid) (DTNB, Ellman's reagent) reaction. Samples containing scavenger (to remove reduced glutathione, GSH) were used to measure oxidised glutathione (GSSG). Glutathione reductase (GR) activity (u/l) was measured as the rate of GSH production at 412 nm. Glutathione peroxidise (GPx) activity (u/l) was measured as the change in optical density (340 nm) following the consumption of NADPH after GSSG production. All assays were purchased from BioAssay Systems (Hayward, California). Clinical data including arterial blood gas analysis were collected on admission. RESULTS: Glutathione reductase activity in horses with strangulating small intestinal lesions was significantly reduced compared to control horses (12.2 +/- 1.1 u/l vs. 15.9 +/- 0.8 u/l, P = 0.03, n = 6) whereas GPx activity did not significantly differ between colic and control horses (155.7 +/- 48.7 u/l vs. 167.3 +/- 30.1 u/l, P = 0.84, n = 6). Total glutathione, reduced or oxidised glutathione did not differ significantly between control and colic horses. A positive correlation existed between GR activity and Ca(2+) (r = 0.93) and K(+) (r = 0.75) whereas a strong negative correlation was present between GR activity and HCO3 (-) (r = -0.92) and PaCO2 (r = -0.96). CONCLUSIONS: Reduced plasma glutathione reductase activity with small intestinal strangulation indicates oxidative stress and may be related to systemic electrolyte/bicarbonate abnormalities. Ethical animal research: Study approval No. VREC219a. Explicit owner informed consent for inclusion of animals in this study was not stated. SOURCE OF FUNDING: Supported by the School of Veterinary Sciences, University of Liverpool. Competing interests: None declared. PMID- 26375861 TI - Why therapies for Alzheimer's disease do not work: Do we have consensus over the path to follow? AB - Alzheimer's disease (AD) represents a personal tragedy of enormous magnitude, which imposes a daunting worldwide challenge for health-care providers and society as well. In last five decades, global research in clinics and laboratories has illuminated many features of this sinister and eventually fatal disease. Notwithstanding this development, the Alzheimer's research apparently has come across a phase of disappointment and a little reservation about the direction to follow. Persistently distressing controversies and a significant number of missing facts shed further uncertainty about the path forward. A detailed description of some of the main controversies in AD research may assist the field towards finding a resolution. Here I reviewed some alarming concerns or controversies related to these primary issues and emphasized on a possible mechanism to settle them. PMID- 26375862 TI - Mitochondrial dynamics regulating chemoresistance in gynecological cancers. AB - Chemoresistance enables cancer cells to evade apoptotic stimuli and leads to poor clinical prognosis. It arises from dysregulation of signaling factors responsible for inducing cell proliferation and death and for modulating the microenvironment. In gynecologic cancers, p53 is a pivotal determinant of cisplatin sensitivity, while BCL-2 family members are associated with taxane sensitivity. Mitochondria fusion and fission dynamics are required for many mitochondrial functions and are also involved in mitochondria-mediated apoptosis, which is closely associated with chemosensitivity. Mitochondrial dynamics are controlled by a number of intracellular proteins, including fusion (Opa1 and mitofusion 1 and 2) and fission proteins (Drp1 and Fis1), which can be proapoptotic or antiapoptotic, depending on the cell types, status, and stimuli from the microenvironment. This paper describes the role of mitochondrial dynamics in the mechanism of chemoresistance and the evidence supporting a significant contribution of a hyperfusion state to chemoresistance in gynecological cancers. Moreover, we discuss our findings showing that enforced fission induces apoptosis of cancer cells and sensitizes them to chemotherapeutic agents. Understanding the regulation of mitochondrial dynamics in chemoresistance may provide insight into new biomarkers that better predict cancer chemosensitivity and may aid the development of effective therapeutic strategies for clinical management of gynecologic cancers. PMID- 26375863 TI - Physiological roles of mitochondrial fission in cultured cells and mouse development. AB - Mitochondria, which are double-membrane organelles thought to have originated through endosymbiosis of bacteria, play important roles in not only energy production, but also cellular signaling, differentiation, and development. The morphology of mitochondria is highly diverse among different tissues, and dynamic changes in mitochondrial morphology have been observed in response to various intracellular signals and stresses. These changes in mitochondrial morphology occur by repeated membrane fusion and fission events, which are regulated by three types of GTPase proteins: OPA1, Mfn1/2, Drp1 in mammalian cells. In recent years, the function and molecular mechanisms of mitochondrial dynamics have been demonstrated in cultured cells; however, the role of mitochondrial fission in maintaining tissue homeostasis remains poorly understood. Here, we review recent advances in research on the physiological role of mitochondrial fission in various differentiated tissue types in mammals. PMID- 26375865 TI - Corrigendum for Ann. N.Y. Acad. Sci. 2015. 1336: 18-35. PMID- 26375866 TI - Corrigendum for Ann. N.Y. Acad. Sci. 2015. 1336: 89-106. PMID- 26375867 TI - Corrigendum for Ann. N.Y. Acad. Sci. 2015. 1336: 109-115. PMID- 26375864 TI - Calcium signaling as a mediator of cell energy demand and a trigger to cell death. AB - Calcium signaling is pivotal to a host of physiological pathways. A rise in calcium concentration almost invariably signals an increased cellular energy demand. Consistent with this, calcium signals mediate a number of pathways that together serve to balance energy supply and demand. In pathological states, calcium signals can precipitate mitochondrial injury and cell death, especially when coupled to energy depletion and oxidative or nitrosative stress. This review explores the mechanisms that couple cell signaling pathways to metabolic regulation or to cell death. The significance of these pathways is exemplified by pathological case studies, such as those showing loss of mitochondrial calcium uptake 1 in patients and ischemia/reperfusion injury. PMID- 26375868 TI - The Effect of Reading Aloud Exercises for Complete Denture Patients during the Functional Rehabilitation Period. AB - PURPOSE: The focus of this study was to evaluate the effect of reading aloud on masticatory performance and patient satisfaction of patients rehabilitated with conventional complete dentures for the first time. MATERIALS AND METHODS: Sixty two edentulous patients who received conventional complete denture treatment for the first time were randomly divided into two equal groups. After insertion of the dentures, patients in group I were asked to read a news report three times per day for 4 weeks, while those in group II did not read. The reading duration increased by 5 minutes per week, from 5 minutes in the first week to 20 minutes in the fourth week. The patients' mouth opening during reading aloud was advised to gradually increase throughout the training project. Two and four weeks after insertion of the dentures, masticatory performance was assessed using the sieving method, and patient satisfaction was measured using a visual analogue scale, which combined the patient's perceptions in relation to comfort, esthetics, stability, ability to talk, and ability to chew. RESULTS: There were significant improvements in masticatory performance with reading aloud exercises after the insertion of complete dentures (p < 0.001) at the 2- and 4-week follow-up visits. Masticatory performance also showed significant improvement within each group in the follow-up periods (p < 0.001). No significant differences were found between the two groups in patient satisfaction (p > 0.05) at 2 weeks, but at 4 weeks, patient satisfaction regarding stability, ability to talk, and ability to chew was significantly higher for group I (p < 0.001). CONCLUSIONS: The results of this study suggest that reading aloud exercises significantly improved early masticatory performance and patient satisfaction for denture wearers who were treated with conventional complete dentures for the first time, and may be a useful clinical application for more effective denture treatment. PMID- 26375869 TI - Cyclic and Linear Monoterpenes in Phospholipid Membranes: Phase Behavior, Bilayer Structure, and Molecular Dynamics. AB - Monoterpenes are abundant in essential oils extracted from plants. These relatively small and hydrophobic molecules have shown important biological functions, including antimicrobial activity and membrane penetration enhancement. The interaction between the monoterpenes and lipid bilayers is considered important to the understanding of the biological functions of monoterpenes. In this study, we investigated the effect of cyclic and linear monoterpenes on the structure and dynamics of lipids in model membranes. We have studied the ternary system 1,2-dimyristoyl-sn-glycero-3-phosphocholine-monoterpene-water as a model with a focus on dehydrated conditions. By combining complementary techniques, including differential scanning calorimetry, solid-state nuclear magnetic resonance, and small- and wide-angle X-ray scattering, bilayer structure, phase transitions, and lipid molecular dynamics were investigated at different water contents. Monoterpenes cause pronounced melting point depression and phase segregation in lipid bilayers, and the extent of these effects depends on the hydration conditions. The addition of a small amount of thymol to the fluid bilayer (volume fraction of 0.03 in the bilayer) leads to an increased order in the acyl chain close to the bilayer interface. The findings are discussed in relation to biological systems and lipid formulations. PMID- 26375870 TI - Dynamics of p53 and Wnt cross talk. AB - We present the mechanism of interaction of Wnt network module, which is responsible for periodic somitogenesis, with p53 regulatory network, which is one of the main regulators of various cellular functions, and switching of various oscillating states by investigating p53-Wnt model. The variation in Nutlin concentration in p53 regulating network drives the Wnt network module to different states, stabilized, damped and sustain oscillation states, and even to cycle arrest. Similarly, the change in Axin2 concentration in Wnt could able to modulate the p53 dynamics at these states. We then solve the set of coupled ordinary differential equations of the model using quasi steady state approximation. We, further, demonstrate the change of p53 and GSK3 interaction rate, due to hypothetical catalytic reaction or external stimuli, can able to regulate the dynamics of the two network modules, and even can control their dynamics to protect the system from cycle arrest (apoptosis). PMID- 26375871 TI - Rare and Severe Maxillofacial Injury Due to Tear Gas Capsules: Report of Three Cases. AB - Tear gases are used by police or armed forces for control of riots or social events or by the general population for private self-defense. These agents are used widely throughout the world, but some harmful effects have reported. In addition, despite well-defined chemical side effects documented in the literature, data are insufficient regarding mechanical injury due to tear gas capsules. We report three cases of severe maxillofacial injury in patients who had these capsules fired from tear gas guns directly to their faces. The capsules penetrated the patients' faces, causing potentially fatal injuries. To our knowledge, reports of this kind of injury related to tear gas capsules are very rare in the literature. In conclusion, tear gas guns may be very dangerous in terms of human health and they may cause severe injuries, especially when they are not used according to strict guidelines. PMID- 26375872 TI - Cellular compatibility of magnetic nanocomposites. AB - OBJECTIVE: To study the cellular compatibility of the magnetic nanocomposite (n HA/PLLA/Fe2O3) and to discuss the biological behaviors of cells including surface adhesion, proliferation, and expression. The present work provides an experimental basis for medical application. METHOD: Rat osteoblasts (OB) were co cultured with the magnetic nanocomposite. Cell proliferation, cell adhesion, and the expression of type I collagen (Col-I) and osteocalcin (OCN) gene were characterized by the cell counting kit-8 (CCK-8) method, scanning electronic microscopy (SEM), and reverse transcription polymerase chain reaction (RT-PCR), respectively. RESULTS: CCK-8 detection showed that there was no difference in cell proliferation on the magnetic nanocomposite between the experimental group and control group (P > 0.05). SEM indicated that a large amount of cells adhered to the surface and in the pores of the magnetic nanocomposite. As the co-culture time increased, the cells adhering to the magnetic nanocomposite showed an obvious increase. RT-PCR detection showed that as the co-culture time increased, the expression of the Col-I gene was enhanced (P 0.05). There was no obvious difference in the expression of the OCN gene (P > 0.05). CONCLUSION: The magnetic nanocomposite is suitable for cell adhesion, growth, and differentiation with a high cellular compatibility. PMID- 26375873 TI - Resveratrol selectively induces apoptosis in malignant cells with the JAK2V617F mutation by inhibiting the JAK2 pathway. AB - SCOPE: Resveratrol is a natural occurring polyphenol with several health promoting activities, including anticancer potential. Here, we analyzed the cytotoxic effects of resveratrol against malignant cells characterized by aberrant activation of the Janus kinase 2 (JAK2). METHODS AND RESULTS: Cell-cycle analysis, proliferation, apoptosis, and Western blotting assays were performed to study the effect of resveratrol on malignant cells exhibiting an excessive activation of the JAK2 pathway secondary to the JAK2(V617F) mutation. Resveratrol inhibited proliferation and induced apoptosis in JAK2(V617F) mutant tumor cells and its selectivity was 1.5-6.9 times greater than that observed in other tumor cells without the JAK2(V617F) mutation. In addition, resveratrol inhibited the phosphorylation of JAK1, JAK2, and Tyk2 and their downstream mediators, including STAT3 and STAT5. In primary cultures, resveratrol treatment inhibited erythroid progenitor colony formation in blood samples obtained from JAK2(V617F) polycythemia vera patients. Moreover, resveratrol synergized with the selective JAK2 inhibitor ruxolitinib, eliminating tumor cells with the JAK2 mutation. CONCLUSION: Resveratrol may have therapeutic potential against myeloproliferative neoplasms associated with the aberrant activation of the JAK2 pathway. PMID- 26375874 TI - Analysis of relationships between the concentrations of total testosterone and dehydroepiandrosterone sulfate and the occurrence of selected metabolic disorders in aging men. AB - OBJECTIVE: The evaluation of relationships between the concentrations of dehydroepiandrosterone sulfate (DHEAS) and total testosterone (TT) and the occurrence of metabolic disorders, including metabolic syndrome (MetS). METHOD: The participants were subjected to anthropometric measurements and were tested for DHEAS, TT, lipid parameters and carbohydrate parameters. RESULT: We observed a lower concentration of DHEAS in the men with hypertension (HT) compared to those without HT. In the men with MetS, HT, overweight and obesity, the concentration of TT was lower than in the men without these problems. We found statistically significant positive correlations (DHEAS- total cholesterol [TCh], DHEAS- low-density lipoprotein [LDL], TT- high-density lipoprotein [HDL], TT waist-to-hip ratio [WHR]) and negative correlations (DHEAS-age, TT-body weight, TT- body mass index [BMI], TT-abdominal circumference [AC], TT-hip circumference [HC], TT- triglyceride [TG], TT- fasting plasma glucose [FPG], TT- serum insulin levels [I], TT- Homeostasis Model Assessment-Insulin Resistance [HOMA-IR]). Using logistic regression it was ascertained that lower TT levels increase the risk of HT, and were also associated with obesity. CONCLUSION: Our research indicates relationships between TT and the occurrence of MetS and its individual components. Excess body weight in men is a factor associated with lower TT levels. It seems necessary to determine TT in men with MetS and overweight or obesity. DHEAS did not show any significant relations with MetS and its parameters. Age was the most crucial factor responsible for the decrease in DHEAS. PMID- 26375875 TI - Influence of water compartmentation and heterogeneous relaxation on quantitative magnetization transfer imaging in rodent brain tumors. AB - PURPOSE: The goal of this study was to investigate the influence of water compartmentation and heterogeneous relaxation properties on quantitative magnetization transfer (qMT) imaging in tissues, and in particular whether a two pool model is sufficient to describe qMT data in brain tumors. METHODS: Computer simulations and in vivo experiments with a series of qMT measurements before and after injection of Gd-DTPA were performed. Both off-resonance pulsed saturation (pulsed) and on-resonance selective inversion recovery (SIR) qMT methods were used, and all data were fit with a two-pool model only. RESULTS: Simulations indicated that a two-pool fitting of four-pool data yielded accurate measures of pool size ratio (PSR) of macromolecular versus free water protons when there were fast transcytolemmal exchange and slow R1 recovery. The fitted in vivo PSR of both pulsed and SIR qMT methods showed no dependence on R1 variations caused by different concentrations of Gd-DTPA during wash-out, whereas the fitted kex (magnetization transfer exchange rate) changed significantly with R1 . CONCLUSION: A two-pool model provides reproducible estimates of PSR in brain tumors independent of relaxation properties in the presence of relatively fast transcytolemmal exchange, whereas estimates of kex are biased by relaxation variations. In addition, estimates of PSR in brain tumors using the pulsed and SIR qMT methods agree well with one another. Magn Reson Med 76:635-644, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26375876 TI - Macronutrient intakes in obese subjects with or without small intestinal bacterial overgrowth: an alimentary survey. AB - OBJECTIVE: Obesity is a multifactorial disorder with a possible microbiota derangement in its pathogenesis. Moreover, in obese patients the likelihood of small intestinal bacterial overgrowth (SIBO) is greater than in controls, although few studies are currently available. This study investigates the prevalence of SIBO and the possible role of dietary macronutrients in obesity. MATERIALS AND METHODS: Sixty obese patients and normal lean controls were enrolled for SIBO detection. Diagnosis of SIBO was performed by a glucose breath test. A 24-hour recall questionnaire was administered to investigate macronutrient daily intake between the two obese patient subgroups (with/without SIBO). RESULTS: The presence of SIBO in obese and controls was respectively 23.3% and 6.6% (p = 0.02, OR = 4.26, 95% Confidence interval = 1.31-13.84). Obese patients with SIBO ingested more carbohydrates (252.75 +/- 30.53 vs 201 +/- 70.76 g/day, p = 0.01), more refined sugars (104.15 +/- 28.69 vs 73.32 +/- 44.93 g/day, p = 0.02) and less total and insoluble fibers (9.6 +/- 1.97 vs 14.65 +/- 8.80 g/day, p = 0.04 and 4.7 +/- 1.11 vs 8.82 +/- 5.80 g/day, p = 0.01, respectively). There were no significant differences in lipid and protein intake between the two groups. CONCLUSIONS: SIBO is widespread in obese subjects. Carbohydrates might promote the development of SIBO in obesity and fibers provide a protective function. Our results suggest a close relationship between diet and SIBO in obesity, thus supporting a possible role for intestinal microbiota. PMID- 26375878 TI - Clinical Research Abstracts of the British Equine Veterinary Association Congress 2015. AB - REASONS FOR PERFORMING STUDY: In cases of laminitis, an increased muscle force or contracture of the deep digital flexor muscle (DDFM) is suggested, but evidence based research is lacking. OBJECTIVES: To test if the DDFM of laminitic equines shows an increased muscle force detectable by needle-EMG including Interference Pattern Analysis (IPA). STUDY DESIGN: Cross-sectional study. METHODS: Three groups consisted of Group 0 (control): 6 Royal Dutch Sport horses, 3 Shetland ponies and one Welsh pony (healthy, sound adults, mean +/- s.d. weight 411 +/- 217 kg). Group 1: 3 Royal Dutch Sport horses, one Friesian, one Haflinger, one Icelandic horse, 2 Welsh ponies, one miniature Appaloosa and 6 Shetland ponies (adults, mean +/- s.d. weight 310 +/- 172 kg) suffering from acute or chronic laminitis. EMG measurements including firing frequency (F) and IPA parameters Turns/Second (T), Amplitude/Turn (M) and Ratio M/T (R) were performed. ANOVA was used to analyse data. P values of P<0.05 were considered significant. RESULTS: Mean +/- s.d. F of Group 0 and Group 1 was 53 +/- 11 and 72 +/- 21 Hz, mean +/- s.d. T was 112 +/- 57 and 106 +/- 42, mean +/- s.d. M was 284 +/- 51 and 254 +/- 38 MUV and mean +/- s.d. R was 0.39 +/- 0.17 and 0.42 +/- 0.16%, respectively. The firing frequency of Group 1 was significantly higher compared to Group 0 (P = 0.02), whereas other differences were not significant. CONCLUSIONS: In human medicine, an increased firing frequency is a characteristic of increased muscle force [1,2]. Thus, the increased firing frequency of the DDFM in case of laminitis suggests an elevated muscle force. As all parameters show a high variance, a repeated study including a larger test group is advised. Ethical animal research: Data collection from controls was approved by the Animal Welfare Committee of Utrecht University, approval number 2008.III.07.061 and 2013.III.01.012. Clinical cases were privately owned and written owner consent was obtained. SOURCE OF FUNDING: None. Competing interests: None declared. PMID- 26375877 TI - Cancer statistics for Hispanics/Latinos, 2015. AB - Cancer is the leading cause of death among Hispanics/Latinos, who represent the largest racial/ethnic minority group in the United States, accounting for 17.4% (55.4 million/318 million) of the total US population in 2014. Every 3 years, the American Cancer Society reports on cancer statistics for Hispanics based on incidence data from the National Cancer Institute, the Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries and mortality data from the National Center for Health Statistics. Among Hispanics in 2015, there will be an estimated 125,900 new cancer cases diagnosed and 37,800 cancer deaths. For all cancers combined, Hispanics have 20% lower incidence rates and 30% lower death rates compared with non-Hispanic whites (NHWs); however, death rates are slightly higher among Hispanics during adolescence (aged 15-19 years). Hispanic cancer rates vary by country of origin and are generally lowest in Mexicans, with the exception of infection-associated cancers. Liver cancer incidence rates in Hispanic men, which are twice those in NHW men, doubled from 1992 to 2012; however, rates in men aged younger than 50 years declined by 43% since 2003, perhaps a bellwether of future trends for this highly fatal cancer. Variations in cancer risk between Hispanics and NHWs, as well as between subpopulations, are driven by differences in exposure to cancer causing infectious agents, rates of screening, and lifestyle patterns. Strategies for reducing cancer risk in Hispanic populations include increasing the uptake of preventive services (e.g., screening and vaccination) and targeted interventions to reduce obesity, tobacco use, and alcohol consumption. PMID- 26375879 TI - Preoperative Treatment With Pazopanib in a Case of Chemotherapy-Resistant Infantile Fibrosarcoma. AB - Clinical and radiological diagnosis of infantile fibrosarcoma (IFS) is challenging because of its similarity to vascular origin tumors. Treatment involves complete resection. Although chemotherapy may allow more conservative resection, treatment guidelines are not strictly defined. One IFS patient with an unresectable tumor had disease progression during chemotherapy. A primary tumor sample showed high VEGFR-1/2/3 and PDGFR-alpha/beta expression. After pazopanib therapy, most tumor showed necrosis within 29 days and could be removed completely, with no relapse in 8 months post-resection. When IFS features hypervascularity, VEGFR and PDGFR expression may be high, thus allowing consideration of VEGFR inhibitors such as pazopanib. PMID- 26375880 TI - Sprouty gain of function disrupts lens cellular processes and growth by restricting RTK signaling. AB - Sprouty proteins function as negative regulators of the receptor tyrosine kinase (RTK)-mediated Ras/Raf/MAPK pathway in many varied physiological and developmental processes, inhibiting growth factor-induced cellular proliferation, migration and differentiation. Like other negative regulators, Sprouty proteins are expressed in various organs during development, including the eye; ubiquitously expressed in the optic vesicle, lens pit, optic cup and lens vesicle. Given the synexpression of different antagonists (e.g, Sprouty, Sef, Spred) in the developing lens, to gain a better understanding of their specific role, in particular, their ability to regulate ocular growth factor signaling in lens cells, we characterized transgenic mice overexpressing Sprouty1 or Sprouty2 in the eye. Overexpression of Sprouty in the lens resulted in reduced lens and eye size during ocular morphogenesis, influenced by changes to the lens epithelium, aberrant fiber cell differentiation and compromised de novo maintenance of the lens capsule. Here we demonstrate an important inhibitory role for Sprouty in the regulation of lens cell proliferation and fiber differentiation in situ, potentially through its ability to modulate FGF- (and even EGF-) mediated MAPK/ERK1/2 signaling in lens cells. Whilst growth factor regulation of lens cell proliferation and fiber differentiation are required for orchestrating lens morphogenesis and growth, in turn, antagonists such as Sprouty are just as important for regulating the intracellular signaling pathways driving lens cellular processes. PMID- 26375881 TI - Assessing the aftermath of an alcohol-fueled weekend: Alcohol-induced DNA damage and faulty repairs may raise the risk of certain cancers, but resveratrol could provide some relief. PMID- 26375882 TI - 2015 Cancer Cytopathology Young Investigator Challenge. PMID- 26375883 TI - Young investigator challenge: The accuracy of the nuclear-to-cytoplasmic ratio estimation among trained morphologists. AB - BACKGROUND: The estimation of the nuclear-to-cytoplasmic ratio (N:C ratio) is an important factor in diagnosing atypia and malignancy in pathological specimens, particularly in cytology. Many algorithms for determining malignant potential make reference to specific, decimal N:C ratios without specifying how the ratio should be measured, with the implication that the observer is intended to estimate this ratio by eye. The authors wanted to determine how accurate trained morphologists (including attending pathologists, pathology residents, and cytotechnologists) are at estimating the N:C ratio without a measuring device. METHODS: Two surveys were prepared containing ideal and real cell images of various N:C ratios. Participants were instructed to select their best estimate from a list of decimal ratios. The data were tabulated and analyzed to determine how accurate the estimates were and whether there was any performance difference between ideal and real images. RESULTS: The absolute and percentage deviation from the actual N:C ratio decreased steadily with increasing N:C ratio. Aggregate performance was found to be closely correlated between real and ideal images, although interobserver variation was not significantly different among participants in the real images quiz, but was significantly different on the ideal images quiz. CONCLUSIONS: Trained morphologists make relatively accurate estimations of the N:C ratio and become increasingly more accurate as the depicted N:C ratio increases. This suggests that including N:C ratio decimals as a criteria for the diagnosis of atypia is valid for high N:C ratios. PMID- 26375885 TI - On local anomaly detection and analysis for clinical pathways. AB - OBJECTIVE: Anomaly detection, as an imperative task for clinical pathway (CP) analysis and improvement, can provide useful and actionable knowledge of interest to clinical experts to be potentially exploited. Existing studies mainly focused on the detection of global anomalous inpatient traces of CPs using the similarity measures in a structured manner, which brings order in the chaos of CPs, may decline the accuracy of similarity measure between inpatient traces, and may distort the efficiency of anomaly detection. In addition, local anomalies that exist in some subsegments of events or behaviors in inpatient traces are easily overlooked by existing approaches since they are designed for detecting global or large anomalies. METHOD: In this study, we employ a probabilistic topic model to discover underlying treatment patterns, and assume any significant unexplainable deviations from the normal behaviors surmised by the derived patterns are strongly correlated with anomalous behaviours. In this way, we can figure out the detailed local abnormal behaviors and the associations between these anomalies such that diagnostic information on local anomalies can be provided. RESULTS: The proposed approach is evaluated via a clinical data-set, including 2954 unstable angina patient traces and 483,349 clinical events, extracted from a Chinese hospital. Using the proposed method, local anomalies are detected from the log. In addition, the identified associations between the detected local anomalies are derived from the log, which lead to clinical concern on the reason resulting in these anomalies in CPs. The correctness of the proposed approach has been evaluated by three experience cardiologists of the hospital. For four types of local anomalies (i.e., unexpected events, early events, delay events, and absent events), the proposed approach achieves 94%, 71% 77%, and 93.2% in terms of recall. This is quite remarkable as we do not use a prior knowledge. CONCLUSION: Substantial experimental results show that the proposed approach can effectively detect local anomalies in CPs, and also provide diagnostic information on the detected anomalies in an informative manner. PMID- 26375886 TI - Peer review and the Three Rs: A challenge to integrity? PMID- 26375887 TI - Summary and analysis of the currently existing literature data on metal-based nanoparticles published for selected aquatic organisms: Applicability for toxicity prediction by (Q)SARs. AB - This review establishes an inventory of existing toxicity data on nanoparticles (NPs) with the purpose of developing (Quantitative) Structure-Activity Relationships for NPs (nano-[Q]SARs), and also of maximising the use of scientific sources for NP risk assessment. From a data search carried out on 27 February 2014, a total of 910 publications were retrieved from the Web of ScienceTM Core Collection, and a database comprising 886 records of toxicity endpoints, based on these publications, was built. The test organisms mainly comprised bacteria, algae, yeast, protozoa, nematoda, crustacea and fish. The NPs consisted mostly of metals, metal oxides, nanocomposites and quantum dots. The data were analysed further, in order to: a) categorise each toxicity endpoint and the biological effects triggered by the NPs; b) survey the characterisation of the NPs used; and c) assess whether the data were suitable for nano-(Q)SAR development. Despite the efforts of numerous scientific programmes on nanomaterial safety and design, our study concluded that lack of data consistency prevents the use of experimental data in developing and validating nano-(Q)SARs. Finally, an outlook on the future of nano-(Q)SAR development is provided. PMID- 26375888 TI - More noise does not mean more precision: A review of Aldenberg and Rorije (2013). AB - This paper provides a critical review of recently published work that suggests that the precision of hazardous concentration estimates from Species Sensitivity Distributions (SSDs) is improved when the uncertainty in the input data is taken into account. Our review confirms that this counter-intuitive result is indeed incorrect. PMID- 26375889 TI - A critical assessment of the scientific basis, and implementation, of regulations for the safety assessment and marketing of innovative tobacco-related products. AB - Our scientific, logistical, ethical and animal welfare-related concerns about the latest US Food and Drug Administration (FDA) regulations for existing and so called 'new' tobacco products, aimed at reducing harmful exposures, are explained. Such claims for sales in the USA now have to be based on a wide range of information, a key part of which will increasingly be data on safety and risk. One of the pathways to achieve marketing authorisation is to demonstrate substantial equivalence (SE) with benchmark products, called predicates. However, the regulations are insufficiently transparent with regard to: a) a rationale for the cut-off date for 'old' and 'new' products, and for exempting the former from regulation; b) the scientific validity and operation of SE; c) options for product labelling to circumvent SE; d) the experimental data required to support, and criteria to judge, a claim; and e) a strategy for risk assessment/management. Scientific problems related to the traditional animal methods used in respiratory disease and inhalation toxicology, and the use of quantitative comparators of toxicity, such as the No Observed Adverse Effect Level, are discussed. We review the advantages of relevant in vitro, mechanism-based, target tissue-oriented technologies, which an advisory report of the Institute of Medicine of the US National Academy of Sciences largely overlooked. These benefits include: a) the availability, for every major site in the respiratory tract, of organotypic human cell-based tissue culture systems, many of which are already being used by the industry; b) the accurate determination of concentrations of test materials received by target cells; c) methods for exposure to particulate and vapour phases of smoke, separately or combined; d) the ability to study tissue-specific biotransformation; and e) the use of modern, human-focused methodologies, unaffected by species differences. How data extrapolation, for risk assessment, from tissue culture to the whole animal, could be addressed, is also discussed. A cost (to animal welfare)-benefit (to society, including industry and consumers) analysis was conducted, taking into account the above information; the potential for animal suffering; the extensive data already available; the existence of other, less hazardous forms of nicotine delivery; the fact that much data will be generated solely for benchmarking; and that many smokers (especially nicotine dependents) ignore health warnings. It is concluded that, in common with policies of several tobacco companies and countries, the use of laboratory animals for tobacco testing is very difficult, if not impossible, to justify. Instead, we propose and argue for an integrated testing scheme, starting with extensive chemical analysis of the ingredients and by-products associated with the use of tobacco products and their toxicity, followed by use of in vitro systems and early clinical studies (involving specific biomarkers) with weight-of-evidence assessments at each stage. Appropriate adjustment factors could be developed to enable concentration-response data obtained in vitro, with the other information generated by the strategy, to enable the FDA to meet its objectives. It is hoped that our intentionally provocative ideas will stimulate further debate on this contentious area of regulatory testing and public safety. PMID- 26375890 TI - The use of 3-D models as alternatives to animal testing. PMID- 26375891 TI - Development and validation of a low-fidelity simulator to suture a laparotomy in rabbits. PMID- 26375892 TI - 18. Rationalisation and intellectualisation. PMID- 26375894 TI - Structural disorder: a tool for housekeeping proteins performing tissue-specific interactions. AB - An interaction between a pair of proteins unique for a particular tissue is denoted as a tissue-specific interaction (TSI). Tissue-specific (TS) proteins always perform TSIs with a limited number of interacting partners. However, it has been claimed that housekeeping (HK) proteins frequently take part in TSIs. This is actually an unusual phenomenon. How a single HK protein mediates TSIs - remains an interesting yet an unsolved question. We have hypothesized that HK proteins have attained a high degree of structural flexibility to modulate TSIs efficiently. We have observed that HK proteins are selected to be intrinsically disordered compared to TS proteins. Therefore, the purposeful adaptation of structural disorder brings out special advantages for HK proteins compared to TS proteins. We have demonstrated that TSIs may play vital roles in shaping the molecular adaptation of disordered regions within HK proteins. We also have noticed that HK proteins, mediating a huge number of TSIs, have a greater portion of their interacting interfaces overlapped with the adjacent disordered segment. Moreover, these HK proteins, mediating TSIs, preferably adapt single domain (SD). We have concluded that HK proteins adapt a high degree of structural flexibility to mediate TSIs. Besides, having a SD along with structural flexibility is more economic than maintaining multiple domains with a rigid structure. This assists them in attaining various structural conformations upon binding to their partners, thereby designing an economically optimum molecular system. PMID- 26375893 TI - Role of bacteria in leukocyte adhesion deficiency-associated periodontitis. AB - Leukocyte adhesion deficiency Type I (LAD-I)-associated periodontitis is an aggressive form of inflammatory bone loss that has been historically attributed to lack of neutrophil surveillance of the periodontal infection. However, this form of periodontitis has proven unresponsive to antibiotics and/or mechanical removal of the tooth-associated biofilm. Recent studies in LAD-I patients and relevant animal models have shown that the fundamental cause of LAD-I periodontitis involves dysregulation of a granulopoietic cytokine cascade. This cascade includes interleukin IL-23 (IL-23) and IL-17 that drive inflammatory bone loss in LAD-I patients and animal models and, moreover, foster a nutritionally favorable environment for bacterial growth and development of a compositionally unique microbiome. Although the lack of neutrophil surveillance in the periodontal pockets might be expected to lead to uncontrolled bacterial invasion of the underlying connective tissue, microbiological analyses of gingival biopsies from LAD-I patients did not reveal tissue-invasive infection. However, bacterial lipopolysaccharide was shown to translocate into the lesions of LAD-I periodontitis. It is concluded that the bacteria serve as initial triggers for local immunopathology through translocation of bacterial products into the underlying tissues where they unleash the dysregulated IL-23-IL-17 axis. Subsequently, the IL-23/IL-17 inflammatory response sustains and shapes a unique local microbiome which, in turn, can further exacerbate inflammation and bone loss in the susceptible host. PMID- 26375896 TI - New Records of Species of Macrovalvitrematidae Yamaguti, 1963 (Monogenea) from Puerto Rico Including One New Genus and Two New Species. AB - New records of Macrovalvitrematidae Yamaguti, 1963 are reported from Puerto Rico including Buccamagna archosarga n. gen., n. sp. from the western Atlantic sea bream Archosargus rhomboidalis, Pseudotagia pomadasys n. sp. from the roughneck grunt Pomadasys corvinaeformis, and new locality records for the species Neopterinotrematoides avaginata Suriano, 1975 and Macrovalvitrema argentinensis (Suriano, 1975) n. comb. from the whitemouth croaker Micropogonias furnieri . Buccamagna n. gen. is based on the anterior end and the oral disc being much larger and wider than width of the body proper, by having a pair of rectangular and sclerotized oral suckers, by lacking a pharynx, by having an excessive narrowness in the proximal area of both valves, and by having both valves of the 3 pairs of large clamps armed with several accessory sclerites. Pseudotagia pomadasys n. sp. is distinguished by the absence of serration of lateral sclerites and the relative size of the clamps, having the 2 larger pairs positioned centrally in the haptor and the 2 smaller pairs in the outer positions. Macrovalvitrematoides and Neomacrovalvitrema are synonymized with Macrovalvitrema, which is amended to include Macrovalvitrema micropogoni (Pearse, 1949) n. comb. and Macrovalvitrema argentinensis (Suriano, 1975) n. comb. based on recognition of identical clamp morphologies. In this study the clamp is emphasized as the key taxonomic character for macrovalvitrematid genera. Except for Pseudotagia, the Macrovalvitrematidae have distinctively longer than wide clamps (at least twice as long as wide); with the dorsal valve larger and with a more-complex skeletal structure (g1, g2, i, k, and f sclerites) than ventral valve (c and d sclerites); and 2 clamp morphologies. Characteristics not previously described but present in all macrovalvitrematid monogeneans except Pseudotagia included: (1) asymmetrical plate (plate b) along the ventral valve with a thin fissure on one side, and (2) mirror image arrangement of the pairs of clamps. PMID- 26375897 TI - Evaluation of a novel repetitive gas-enhanced permeation test for restoration leakage determination after thermo-mechanical loading. AB - OBJECTIVES: To assess leakage of class-I restorations using a gas-enhanced permeation test (GEPT) as compared with conventional SEM or dye analysis. MATERIALS AND METHODS: Pressure differences over time and penetrating water volumes were measured simultaneously in a two-chamber system (GEPT) before and after class I cavity preparation in 30 molars. Ten teeth were restored with a composite restoration without bonding (A1), a composite restoration with bonding (A2) or a ceramic indirect restoration (B). Five intact teeth served as controls (C). Another GEPT measurement was performed and impressions were taken. Teeth were subjected to thermodynamic loading (1 200 000 cycles) and final GEPT measurements and impressions were made. SEM evaluation of the marginal continuity was performed and teeth were subjected to a Fuchsin dye penetration test. Spearman's rank test was used to compare results from different tests. RESULTS: The GEPT and SEM values did not correlate before loading (0.359, p = 0.051), but significantly correlated afterwards (0.662, p < 0.0001). The correlations between the Fuchsin dye penetration test and GEPT and SEM surface marginal analysis were significant (0.777 and 0.534, p-values < 0.0001 and 0.002, respectively). CONCLUSIONS: SEM marginal analysis was mainly limited in reflecting the surface restoration integrity. GEPT evaluation may, therefore, serve as a tool to non destructively assess restoration sub-surface integrity over time. CLINICAL RELEVANCE: The current study provided proof that restoration margin quality does not necessarily reflect its leakage behaviour. PMID- 26375898 TI - Controversies in laparoscopic ventral hernia repair. AB - BACKGROUND: The introduction of laparoscopy as a surgical technique provided a method preventing major abdominal wall incisions and improving recovery of the patient after surgery. In abdominal wall surgery laparoscopic ventral hernia repair has proven to be at least as save as open repair. However, the technique of laparoscopic ventral hernia repair has not been standardized. Despite all the research that has been conducted and all the articles that were published, there still seems to be absence of consensus about the best method to repair a ventral hernia. AIM: To review knowledge on incisional hernias and discuss several controversies regarding the laparoscopic management of ventral hernias. METHODS: A review of the literature was undertaken. RESULTS: A search identified twenty records: six RCTs on incisional hernias, five RCTs on ventral hernias and nine reviews or meta-analyses. Interpretation of the scientific data is difficult because the outcomes in literature are often based on pooled data of primary ventral hernias and incisional ventral hernias. Controversy remains regarding the optimal laparoscopic management of ventral hernias in terms of selection of patients for laparoscopic repair, optimal technique, outcomes and cost-efficacy. CONCLUSION: Lack of evidence allows persisting controversies in laparoscopic ventral hernia repair. RCTs and registries are necessary to document efficacy, morbidity, quality of life and costs during a sufficient period of time to provide clinicians with the evidence required to make the right choice for the best surgical technique. PMID- 26375899 TI - Controversies in the management of early rectal cancer. AB - Proctectomy with total mesorectal excision (TME) is the gold standard for rectal cancer surgical management, as it offers optimal oncologic results. However, this radical procedure is impaired by significant drawbacks, including temporary diverting stoma, risk of permanent stoma, high risk of postoperative morbidity, and long-term risk of postoperative bowel, urinary, and sexual disorders. These results led some authors to define "early rectal cancer" in an attempt to propose alternative strategies such as local excision in order to avoid radical surgery. Indeed, local surgery does not involve diverting stoma, has the advantage of sphincter-preservation even for very low rectal tumors, is associated with very good short-term results and accounts for a nearly nil long-term risk of bowel dysfunction or urogenital disorders. However, local excision, as opposed to TME, does not allow lymph node resection and staging. Its indication has therefore been the subject of debate. Finally, the recent description of organ preservation strategies, which concept lies in the avoidance of radical surgery, has recently been the subject of a high number of publications, including some poor-prognosis early rectal cancer. Recently, early rectal cancer has therefore become an intense field of research. In this review, we will assess described strategies and controversies regarding early rectal cancer management. PMID- 26375901 TI - 2015 AMCA Presidential Address. PMID- 26375900 TI - Force-Time Entropy of Isometric Impulse. AB - The relation between force and temporal variability in discrete impulse production has been viewed as independent (R. A. Schmidt, H. Zelaznik, B. Hawkins, J. S. Frank, & J. T. Quinn, 1979 ) or dependent on the rate of force (L. G. Carlton & K. M. Newell, 1993 ). Two experiments in an isometric single finger force task investigated the joint force-time entropy with (a) fixed time to peak force and different percentages of force level and (b) fixed percentage of force level and different times to peak force. The results showed that the peak force variability increased either with the increment of force level or through a shorter time to peak force that also reduced timing error variability. The peak force entropy and entropy of time to peak force increased on the respective dimension as the parameter conditions approached either maximum force or a minimum rate of force production. The findings show that force error and timing error are dependent but complementary when considered in the same framework with the joint force-time entropy at a minimum in the middle parameter range of discrete impulse. PMID- 26375902 TI - Schools as Potential Risk Sites for Vector-Borne Disease Transmission: Mosquito Vectors in Rural Schools in Two Municipalities in Colombia. AB - Dengue and other vector-borne diseases are of great public health importance in Colombia. Vector surveillance and control activities are often focused at the household level. Little is known about the importance of nonhousehold sites, including schools, in maintaining vector-borne disease transmission. The objectives of this paper were to determine the mosquito species composition in rural schools in 2 municipalities in Colombia and to assess the potential risk of vector-borne disease transmission in school settings. Entomological surveys were carried out in rural schools during the dry and rainy seasons of 2011. A total of 12 mosquito species were found: Aedes aegypti, Anopheles pseudopunctipennis, Culex coronator, Cx. quinquefasciatus, and Limatus durhamii in both immature and adult forms; Ae. fluviatilis, Cx. nigripalpus, Cx. corniger, and Psorophora ferox in immature forms only; and Ae. angustivittatus, Haemagogus equinus, and Trichoprosopon lampropus in adult forms only. The most common mosquito species was Cx. quinquefasciatus. Classrooms contained the greatest abundance of adult female Ae. aegypti and Cx. quinquefasciatus. The most common Ae. aegypti breeding sites were containers classified as "others" (e.g., cans), followed by containers used for water storage. A high level of Ae. aegypti infestation was found during the wet season. Our results suggest that rural schools are potentially important foci for the transmission of dengue and other mosquito-borne diseases. We propose that public health programs should be implemented in rural schools to prevent vector-borne diseases. PMID- 26375903 TI - Modification of the Suna Trap for Improved Survival and Quality of Mosquitoes in Support of Epidemiological Studies. AB - Monitoring adult mosquito populations provides information that is critical for assessing risk of vector-borne disease transmission. The recently developed Suna trap was found to be a very effective trap when baited with an attractive odor blend. A modification of this trap was tested to improve its function as a tool for monitoring mosquito populations, including Anopheles coluzzii (An. gambiae sensu stricto molecular form M), Aedes aegypti, and Culex pipiens. The modified Suna trap (Suna-M) was altered by changing the position of the catch bag and the inclusion of a holding chamber in attempts to increase trapping efficacy and enhance the survival of mosquitoes. Each adaptation was tested in a dual-choice setup in a climate-controlled room against the original Suna trap and against 4 standard monitoring methods: the BG-sentinel (BGS), Centers for Disease Control and Prevention (CDC) light trap, Mosquito Magnet X (MM-X) trap, and human landing catch (HLC). No differences in trapping efficacy were observed between the original Suna trap and modified version; however, a version in which the funnel was extended with a box and supplemented with moistened cotton wool increased mosquito survival from 6.5% to 78.0% over 24 h. The HLC and BGS trap outperformed the Suna-M trap, whereas the MM-X and commonly used CDC light trap performed significantly less well than the Suna-M trap in the dual-choice setup. The performance of the Suna-M trap equaled the performance of the original Suna trap and could therefore be used for monitoring purposes. Although the HLC and BGS trap achieved higher catch sizes, the Suna trap has the advantage that it is standardized, does not place humans at risk, and is weather resistant. Field studies should be conducted to confirm that the Suna-M trap, baited with the odor blend, is an efficient and standardized tool to measure both indoor and outdoor disease transmission risk for a range of vector-borne diseases. PMID- 26375904 TI - La Crosse Encephalitis Virus Infection in Field-Collected Aedes albopictus, Aedes japonicus, and Aedes triseriatus in Tennessee. AB - La Crosse virus (LACV) is a mosquito-borne virus and a major cause of pediatric encephalitis in the USA. La Crosse virus emerged in Tennessee and other states in the Appalachian region in 1997. We investigated LACV infection rates and seasonal abundances of the native mosquito vector, Aedes triseriatus, and 2 recently introduced mosquito species, Ae. albopictus and Ae. japonicus, in an emerging disease focus in Tennessee. Mosquitoes were collected using multiple trapping methods specific for Aedes mosquitoes at recent human case sites. Mosquito pools were tested via reverse transcriptase-polymerase chain reaction (RT-PCR) of the S segment to detect multiple Bunyamwera and California serogroup viruses, including LACV, as well as real-time RT-PCR of the M segment. A total of 54 mosquito pools were positive, including wild-caught adult females and laboratory-reared adults, demonstrating transovarial transmission in all 3 species. Maximum likelihood estimates (per 1,000 mosquitoes) were 2.72 for Ae. triseriatus, 3.01 for Ae. albopictus, and 0.63 for Ae. japonicus. We conclude that Ae. triseriatus and Ae. albopictus are important LACV vectors and that Ae. japonicus also may be involved in virus maintenance and transmission. PMID- 26375905 TI - Assessing Carbon Dioxide and Synthetic Lure-Baited Traps for Dengue and Chikungunya Vector Surveillance (3). AB - The Aedes mosquito vectors of dengue virus (DENV) and chikungunya virus (CHIKV) are attracted to specific host cues that are not generated by traditional light traps. For this reason multiple companies have designed traps to specifically target those species. Recently the standard trap for DENV and CHIKV vectors, the BG-Sentinel (BGS) trap, has been remodeled to be more durable and better suited for use in harsh field conditions, common during military operations, and relabeled the BG-Sentinel 2 (BGS2). This new trap was evaluated against the standard Centers for Disease Control and Prevention (CDC) light trap, Zumba Trap, and BG-Mosquitito Trap to determine relative effectiveness in collecting adult Aedes aegypti and Ae. albopictus. Evaluations were conducted under semifield and field conditions in suburban areas in northeastern Florida from May to August 2014. The BGS2 trap collected more DENV and CHIKV vectors than the standard CDC light trap, Zumba Trap, and BG-Mosquitito Trap, but attracted fewer species, while the BG-Mosquitito Trap attracted the greatest number of mosquito species. PMID- 26375906 TI - A Comparison of Carbon Dioxide Sources for Mosquito Capture in Centers for Disease Control and Prevention Light Traps on the Florida Gulf Coast (1). AB - Traditional sources of carbon dioxide (CO2), dry ice, and compressed gas, were tested against 3 combinations of food-grade reagents known to generate CO2using a compact, lightweight generator delivery system with Centers for Disease Control and Prevention light traps. Three 6 * 6 Latin square trials were completed near the Florida Gulf Coast in the Lower Suwannee Wildlife Refuge during the summer of 2013, collecting a total of 31,632 female mosquitoes. Treatments included dry ice, compressed CO2gas, a control trap (no CO2), citric acid + sodium bicarbonate, vinegar + sodium bicarbonate, and yeast + sugar. Decreasing order of trap collections (treatment mean number of mosquitoes per trap night +/- standard error) were dry ice 773.5 (+/- 110.1) > compressed gas 440.7 (+/- 42.3) > citric acid + sodium bicarbonate 197.6 (+/- 30.4), yeast + sugar 153.6 (+/- 27.4) > vinegar + sodium bicarbonate 109.6 (+/- 16.2) > control 82.4 (+/- 14.0). A 2-way Kruskal-Wallis analysis by treatment, site, and treatment * site interaction identified significant differences between all treatments. Although dry ice and compressed CO2gas collected significantly more mosquitoes than other combinations (P < 0.05), use of citric acid and sodium bicarbonate or yeast and sugar greatly outperformed unbaited traps and offer a good alternative to dry ice and compressed gas in areas where these agents are not readily available or are difficult to obtain due to logistical constraints. An inexpensive, portable CO2generator for use with food-grade reagents is described. PMID- 26375907 TI - Evaluation of Bacillus thuringiensis israelensis as a Control Agent for Adult Anopheles gambiae. AB - Unlike the application of Bacillus thuringiensis israelensis (Bti) for the control of larval mosquitoes, studies of its effects on adults, for its possible use in attractive toxic sugar baits, have resulted in conflicting results. Five species have shown a decrease in adult survival due to Bti ingestion, whereas adults of Anopheles arabiensis have not. We sought to determine if ingestion of Bti by adults of Anopheles gambiae, a sibling species of An. arabiensis, increases their mortality. Laboratory-reared adults were provided continuously from emergence with water only, a sucrose solution, or a Bti suspension in sucrose solution. After 3 days, the Bti suspension was replaced with untainted sucrose solution. The mosquitoes with only water were all dead by day 3. The survivorships of those in the sucrose and sucrose-Bti treatments were insignificantly different, both with an LT50 (Lethal Time, time until 50% of individuals died) of 25 days. The results support the conclusion that adult survivorship of An. gambiae-complex members is unaffected by the ingestion of Bti in sugar meals. PMID- 26375908 TI - A Technical Review of MULV-Disp, a Recent Mosquito Ultra-Low Volume Pesticide Spray Dispersion Model. AB - The authors of a recently published paper summarized the development of a regression model for ground-based ultra-low volume applications, suggesting that their model was sufficiently verified that it could be used extensively for mosquito control. These authors claimed that their statistical model was superior in its predictive capability to the extensively developed and Environmental Protection Agency-validated AGDISP mechanistic model. In this technical review, the assumptions, reduction and interpretation of data, and conclusions reached with regard to their model are discussed, and explicit misstatements and incorrect mathematical relationships are pointed out. Two published versions of the model regression equation give substantially different results without explanation. Petri dish collection was used for very small droplets, with no mention of collection efficiency. Meteorological data were misused based on manufacturer's specification of instrument accuracy. We strongly disagree with many of the model results and show that the model misrepresents the actual behavior of aerosol sprays applied in the manner tested. PMID- 26375909 TI - First Record and Larval Habitat Description of Culex (Melanoconion) pilosus from Buenos Aires Province, Argentina. AB - Larvae of Culex (Melanoconion) pilosus were collected during February-April 2014 in temporary pools in "Bosques de Ezeiza," a large forested park, near Buenos Aires city, Argentina. This is the first record in Buenos Aires Province, extending the distribution of this species 380 km to the south. Regarding habitat use, Cx. (Mel.) pilosus is a generalist, although a slight association of larval abundances with pools of lower pH and higher vegetation cover was observed. The comparison of larval instars of Cx. (Mel.) pilosus with those of other genera suggests a life-history strategy similar to that of floodwater mosquitoes. PMID- 26375910 TI - Arbovirus Surveillance and First Report of Chikungunya Virus in Wild Populations of Aedes aegypti from Guerrero, Mexico. AB - We carried out dengue (DENV) and chikungunya virus (CHIKV) surveillance in wild populations of Aedes aegypti from Guerrero, Mexico, from 2012 to 2014 following a standard national protocol of the Mexican Dengue Control Program. A total of 284 pools (15-30 specimens/pool) of female mosquitoes were tested with real-time reverse transcriptase-polymerase chain reaction to detect DENV and CHIKV. We report for the 1st time the detection of CHIKV from field-collected mosquitoes at Acapulco and Juchitan in 2014. Results from DENV are also reported. PMID- 26375911 TI - Passive Baited Sequential Filth Fly Trap. AB - Filth fly control measures may be optimized with a better understanding of fly population dynamics measured throughout the day. We describe the modification of a commercial motorized sequential mosquito trap to accept liquid odorous bait and leverage a classic inverted-cone design to passively confine flies in 8 modified collection bottles corresponding to 8 intervals. Efficacy trials in a hot-arid desert environment indicate no significant difference (P = 0.896) between the modified sequential trap and a Rid-Max(r) fly trap. PMID- 26375912 TI - Assessment of Reactive Catch Basin Larvicide Treatments Toward Improved Water Quality Using FourStar((r)) Briquets and CocoBearTM Larvicide Oil. AB - Because it is often logistically impossible to monitor all catch basins within an operational area, local mosquito control programs will preemptively treat catch basins with larvicides each season. However, these larvicides can, ostensibly, be considered water quality pollutants. To experimentally reduce the use of larvicides toward improving water quality, 30 basins within a small 0.7-km(2) residential area were monitored weekly for the presence of larvae and pupae for 14 wk in the summer of 2013. Once a basin was found to reach a threshold of 12 mosquitoes per dip sample, it received a FourStar(r) Briquet (a 180-day briquet formulation of 6% Bacillus sphaericus and 1% B. thuringiensis israelensis). Each week a FourStar-treated basin surpassed this threshold, it was treated with an application of CocoBearTM oil (10% mineral oil). By the end of trials, all but one basin received a briquet and 13 required at least 4 treatments of CocoBear, suggesting that preemptive treatment is appropriate for the study area. PMID- 26375913 TI - Mosquito Vector Biology and Control in Latin America-A 25TH Symposium. AB - The 25th Annual Latin American Symposium presented by the American Mosquito Control Association (AMCA) was held as part of the 81st Annual Meeting in New Orleans, LA, in March 2015. The principal objective, as for the previous 24 symposia, was to promote participation in the AMCA by vector control specialists, public health workers, and academicians from Latin America. This publication includes summaries of 24 presentations that were given orally in Spanish by participants from Colombia, Mexico, and the USA. Topics addressed in the symposium included: surveillance, operations, ecology, chemical control, studies of dengue viruses, and insecticide resistance. Insect vectors included Aedes, Culex, and Anopheles mosquitoes in addition to phlebotomine sand flies and triatomine bugs. PMID- 26375916 TI - Analysis of car-to-bicycle approach patterns for developing active safety devices. AB - OBJECTIVE: To reduce the severity of injuries and the number of cyclist deaths in traffic accidents, active safety devices providing cyclist detection are considered to be effective countermeasures. The features of car-to-bicycle collisions need to be known in detail to develop such safety devices. METHODS: The study investigated near-miss situations captured by drive recorders installed in passenger cars. Because similarities in the approach patterns between near miss incidents and real-world fatal cyclist accidents in Japan were confirmed, we analyzed the 229 near-miss incident data via video capturing bicycles crossing the road in front of forward-moving cars. Using a video frame captured by a drive recorder, the time to collision (TTC) was calculated from the car's velocity and the distance between the car and bicycle at the moment when the bicycle initially appeared. RESULTS: The average TTC in the cases where bicycles emerged from behind obstructions was shorter than that in the cases where drivers had unobstructed views of the bicycles. In comparing the TTC of car-to-bicycle near miss incidents to the previously obtained results of car-to-pedestrian near-miss incidents, it was determined that the average TTC in car-to-bicycle near-miss incidents was significantly longer than that in car-to-pedestrian near-miss incidents. CONCLUSIONS: When considering the TTC in the test protocol of evaluation for safety performance of active safety devices, we propose individual TTCs for evaluation of cyclist and pedestrian detections, respectively. In the test protocols, the following 2 scenarios should be employed: bicycle emerging from behind an unobstructed view and bicycle emerging from behind obstructions. PMID- 26375917 TI - Prevalence of behavior problems and associated factors in preschool children from the city of Salvador, state of Bahia, Brazil. AB - OBJECTIVE: To identify the prevalence of internalizing and externalizing behavior problems among preschoolers from the city of Salvador, state of Bahia, Brazil, and their associations with maternal mental health and family characteristics. METHODS: This was a cross-sectional study of 349 children aged 49 to 72 months, randomly selected from 20,000 households representing the range of socioeconomic and environmental conditions in Salvador. In 1999, we assessed sociodemographic variables and family environment characteristics. In 2001, we used the Child Behavior Checklist to measure and describe the frequencies of behavior problems. We conducted bivariate and multivariate analysis to estimate associations between family and maternal factors and prevalence of behavior problems. RESULTS: The overall prevalence of behavior problems was 23.5%. The prevalence of internalizing problems was 9.7%, and that of externalizing problems, 25.2%. Behavior problems were associated with several maternal mental health variables, namely: presence of at least one psychiatric diagnosis (odds radio [OR] 3.01, 95%CI 1.75-5.18), anxiety disorder (OR 2.06, 95%CI 1.20-3.46), affective disorder (OR 2.10, 95%CI 1.21-3.65), and mental health disorders due to use of psychoactive substances (OR 2.31, 95%CI 1.18-4.55). CONCLUSION: The observed prevalence of child behavior problems fell within the range reported in previous studies. Maternal mental health is an important risk factor for behavior problems in preschool-aged children. PMID- 26375918 TI - Effects of REM sleep restriction during pregnancy on rodent maternal behavior. AB - OBJECTIVE: To evaluate the effects of sleep restriction during pregnancy on maternal care and maternal aggression in a rodent model. METHODS: Twenty-three female Wistar rats were assigned to one of two groups: control (n=12) or sleep restriction (n=11) during the entire pregnancy. At the fifth postpartum day, the animals were subjected to the resident-intruder paradigm and to the pup retrieval test. RESULTS: Sleep restriction during pregnancy had no direct effects on maternal care. Regarding aggressive behavior, defensive aggression was increased by sleep loss, with a lower responsiveness threshold to hostile environmental stimuli. Sleep deprivation during gestation also reduced self-grooming behavior. CONCLUSION: Taking increased self-grooming as a behavioral correlate of anxiety in rodents, this study provides evidence that lactating dams were in a condition of reduced anxiety. From an adaptive perspective, this pattern of stress response may function to ensure proper maternal behavior, thereby guaranteeing the survival and viability of the litter. Under a translational perspective, the present article confronts the importance of biological and adaptive features to rodent maternal behavior with the relevance of sociocultural factors to the human mother-infant relationship and to the onset of postpartum depression. PMID- 26375919 TI - A 20-week program of resistance or concurrent exercise improves symptoms of schizophrenia: results of a blind, randomized controlled trial. AB - OBJECTIVE: To evaluate the effects of 20 weeks of resistance and concurrent training on psychotic and depressive symptoms, quality of life outcomes, and serum IGF-1, IGFBP-3, and brain-derived neurotrophic factor (BDNF) concentrations in patients with schizophrenia. METHODS: In this blind, randomized controlled clinical trial, 34 patients with schizophrenia were assigned to one of three groups: control (CTRL, n=13), resistance exercise (RESEX, n=12), or concurrent exercise (CONCEX, n=9). Symptoms, quality of life, strength, and other variables were assessed. RESULTS: A significant time-by-group interaction was found for the RESEX and CONCEX groups on the Positive and Negative Syndrome Scale (PANSS) total score for disease symptoms (p = 0.007), positive symptoms (p = 0.003), and on the arm extension one-repetition maximum (1RM) test (p = 0.016). In addition, significant improvements on negative symptoms (p = 0.027), on the role-physical domain of the Short Form-36 Health Survey (p = 0.019), and on the chest press 1RM test (p = 0.040) were observed in the RESEX group. No changes were observed for the other variables investigated. CONCLUSIONS: In this sample of patients with schizophrenia, 20 weeks of resistance or concurrent exercise program improved disease symptoms, strength, and quality of life. ClinicalTrials.gov: NCT01674543. PMID- 26375920 TI - Common Variants in Promoter of ADTRP Associate with Early-Onset Coronary Artery Disease in a Southern Han Chinese Population. AB - The first genome-wide association study for coronary artery disease (CAD) in the Han Chinese population, we reported recently, had identified rs6903956 in gene ADTRP on chromosome 6p24.1 as a novel susceptibility locus for CAD. The risk allele of rs6903956 was associated with decreased mRNA expression of ADTRP. To further study the correlation of ADTRP expression and CAD, in this study we evaluated the associations of eight common variants in the expression-regulating regions of ADTRP with CAD in the Southern Han Chinese population. Rs169790 in 3'UTR, rs2076189 in 5'UTR, four SNPs (rs2076188, rs7753407, rs11966356 and rs1018383) in promoter, and two SNPs (rs3734273, rs80355771) in the last intron of ADTRP were genotyped in 1716 CAD patients and 1572 controls. The correlations between these loci and total or early-onset CAD were investigated. None of these loci was discovered to associate with total CAD (P > 0.05). However, with early onset CAD, significant both allelic and genotypic associations of rs7753407, rs11966356 and rs1018383 were identified, after adjustment for risk factors of age, gender, hypertension, diabetes, lipid profiles and smoking (adjusted P < 0.05). A haplotype AGCG (constructed by rs2076188, rs7753407, rs11966356 and rs1018383) was identified to protect subjects from early-onset CAD (OR = 0.332, 95% CI = 0.105-0.879, adjusted P = 0.010). Real-time quantitative reverse transcription polymerase chain reaction assay showed that the risk alleles of the associated loci were significantly associated with decreased expression of ADTRP mRNA. Moreover, the average level of ADTRP mRNA expression in early-onset CAD cases was significantly lower than that in controls. Our results provide new evidence supporting the association of ADTRP with the pathogenesis of early-onset CAD. PMID- 26375921 TI - Parkinson's Disease Case Ascertainment in the EPIC Cohort: The NeuroEPIC4PD Study. AB - BACKGROUND/AIMS: Large epidemiological prospective studies represent an important opportunity for investigating risk factors for rare diseases such as Parkinson's disease (PD). Here we describe the procedures we used for ascertaining PD cases in the EPIC (European Prospective Investigation into Cancer and Nutrition) study. METHODS: The following three-phase procedure was used: (1) elaboration of a NeuroEPIC4PD template for clinical data collection, (2) identification of all potential PD cases via record linkage and (3) validation of the diagnosis through clinical record revision, in a population of 220,494 subjects recruited in 7 European countries. All cases were labelled with the NeuroEPIC4PD diagnoses of 'definite', 'very likely', 'probable', or 'possible' PD. RESULTS: A total of 881 PD cases were identified, with over 2,741,780 person-years of follow-up (199 definite, 275 very likely, 146 probable, and 261 possible). Of these, 734 were incident cases. The mean age at diagnosis was 67.9 years (SD 9.2) and 458 patients (52.0%) were men. Bradykinesia was the most frequent presenting motor sign (76.5%). Tremor-dominant and akinetic rigid forms of PD were the most common types of PD. A total of 289 patients (32.8%) were dead at the time of the last follow-up. CONCLUSIONS: This exercise proved that it is feasible to ascertain PD in large population-based cohort studies and offers a potential framework to be replicated in similar studies. PMID- 26375922 TI - Effects of MTHFR c.677C>T, F2 c.20210G>A and F5 Leiden Polymorphisms in Gastroschisis. AB - BACKGROUND: Gastroschisis is a developmental disorder involving the extrusion of fetal intestines through a defect in the abdominal wall. The mechanism is presumed to be a dual vascular/thrombotic pathogenesis, where normal right umbilical vein involution forms a possible site for thrombosis adjacent to the umbilical ring. PURPOSE: The aim of this study was to demonstrate that the 3 common prothrombotic polymorphisms, MTHFR c.677C>T, F2 c.20210G>A, and F5 Leiden, were elevated in frequency in Indonesian gastroschisis patients. MATERIAL AND METHODS: Three genetic markers were investigated in 46 patients with gastroschisis and 89 ethnicity-matched controls for association studies using polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) or TaqMan Genotyping Assays on genomic DNA. RESULTS: MTHFR c.677C>T showed a significant association with gastroschisis (OR = 2.1, 95% CI = 1.13-3.86; p = .018) but no affected infants had risk alleles for either F2 c.20210G>A or F5 Leiden. Further, the frequency of MTHFR risk allele (T) in patients with maternal age <25 years is marginally significant higher than those in cases with maternal age >=25 years (p = .069) with an OR of 2.7 (95% CI = 0.90-8.07). CONCLUSIONS: MTHFR is a common susceptibility factor for gastroschisis in Indonesia. The increased gastroschisis risk in offspring of younger maternal age suggests the thrombotic pathogenesis model. A founder effect is the most likely explanation for the rarity of the F2 and F5 Leiden polymorphisms in Indonesian population. PMID- 26375924 TI - It's a matter of time: Reframing the development of cognitive control as a modification of the brain's temporal dynamics. AB - Cognitive control is a process that unfolds over time and regulates thought and action in the service of achieving goals and managing unanticipated challenges. Prevailing accounts attribute the protracted development of this mental process to incremental changes in the functional organization of a cognitive control network. Here, we challenge the notion that cognitive control is linked to a topologically static network, and argue that the capacity to manage unanticipated challenges and its development should instead be characterized in terms of inter regional functional coupling dynamics. Ongoing changes in temporal coupling have long represented a fundamental pillar in both empirical and theoretical-based accounts of brain function, but have been largely ignored by traditional neuroimaging methods that assume a fixed functional architecture. There is, however, a growing recognition of the importance of temporal coupling dynamics for brain function, and this has led to rapid innovations in analytic methods. Results in this new frontier of neuroimaging suggest that time-varying changes in connectivity strength and direction exist at the large scale and further, that network patterns, like cognitive control process themselves, are transient and dynamic. PMID- 26375925 TI - Vitamin D Levels in Patients With Type 2 Diabetes Mellitus. AB - BACKGROUND: Vitamin D may influence many diseases, including type 2 diabetes mellitus. PATIENTS AND METHODS: We studied serum levels of 25-hydroxyvitamin D (25(OH)D) and associated characteristics in type 2 diabetic outpatients with pharmacologic treatment attended in internal medicine offices in a first-level hospital from Extremadura (Southern Spain). RESULTS: We included a total of 103 patients. Seventy-two patients (69.9%) had serum levels of 25(OH)D lower than 20 ng/mL. There was inverse correlation between serum levels of 25(OH)D and glycosylated hemoglobin (r = -0.74, P = 0.01). In 78 patients without insulin therapy, we found inverse correlation between serum levels of 25(OH)D and fasting serum insulin (r = -0.82, P = 0.001) and Homeostasis Model Assessment-Insulin Resistance (r = -0.51, P < 0.001). CONCLUSIONS: Vitamin D deficiency is common in type 2 diabetic patients. There are inverse correlations between vitamin D and metabolic control and insulin resistance. PMID- 26375923 TI - Cytoreduction and hyperthermic intraperitoneal chemotherapy: The learning curve reassessed. AB - BACKGROUND: CytoReductive Surgery and Hyperthermic IntraPEritoneal Chemotherapy (CRS-HIPEC) is now the preferred treatment of many peritoneal surface malignancies. In this retrospective study we aimed to analyze how several performance indicators changed during the first 100 CRS-HIPEC procedures in hospitals which recently introduced this treatment, and compare those with an experienced institution. METHODS: The first consecutive 100 CRS-HIPEC procedures of three institutions were compared to those of the pioneer hospital. The training provided by the pioneer hospital consisted of hands-on training during the first ten procedures; hereafter guidance was available on consult basis. Operation characteristics, morbidity and completeness of cytoreduction were evaluated by case sequence. Locally-estimated-scatter-plot smoothing was used to evaluate the learning curve. RESULTS: From four institutions 372 cases were included. A macroscopic complete cytoreduction was reached in 66% of the cases in the pioneer hospital and in 86% in the new hospitals (p < 0.001). Complete cytoreduction rates were higher at start off in the new institutions compared with the experienced institution and increased significantly in the first 100 procedures. The new hospitals started with lower morbidity than the experienced hospital, which did not significantly decrease during the study period. CONCLUSION: New institutions that were trained and mentored by an experienced CRS HIPEC hospital performed better from the beginning with regard to complete cytoreduction and morbidity rate with than the experienced center. An improvement in complete cytoreduction rate during the first 100 procedures was observed in the new institutions. PMID- 26375926 TI - Activation of serotonin 5-HT(2C) receptor suppresses behavioral sensitization and naloxone-precipitated withdrawal symptoms in heroin-treated mice. AB - Abuse and dependence to heroin has evolved into a global epidemic as a significant clinical and societal problem with devastating consequences. Repeated exposure to heroin can induce long-lasting behavioral sensitization and withdrawal. Pharmacological activation of 5-HT2C receptors (5-HT2CRs) suppresses psychostimulant-induced drug-seeking and behavioral sensitization. The present study examined the effect of a selective 5-HT2CR agonist lorcaserin on behavioral sensitization and naloxone-precipitated withdrawal symptoms in heroin-treated mice. Male mice received heroin (1.0 mg/kg, s.c.) twice a day for 3 days and then drug treatment was suspended for 5 days. On day 9, a challenge dose of heroin (1.0 mg/kg) was administered to examine the expression of behavioral sensitization. Lorcaserin administered during the development, withdrawal or expression stage suppressed heroin-induced behavioral sensitization on day 9. Another cohort of mice received increasing doses of heroin over a 4.5-day period. Lorcaserin, or the positive control clonidine (an alpha2-adrenoceptor agonist) suppressed naloxone-precipitated withdrawal symptoms in heroin-treated mice. These findings suggest that activation of 5-HT2CRs suppresses behavioral sensitization and withdrawal in heroin-treated mice. Thus, pharmacological activation of 5-HT2CRs may represent a new avenue for the treatment of heroin addiction. PMID- 26375928 TI - The effects of intranasal oxytocin on contagious yawning. AB - Contagious yawning is thought to represent a basic form of empathy involved in state matching. Despite recent evidence in support of this connection, the neurochemical basis of contagious yawning remains largely unknown. Here, we investigate whether intranasal oxytocin, a hormone and neuropeptide involved in empathic processing, bonding and social affiliation, influences contagious yawning among human participants in a laboratory setting. Using a double blind procedure, 60 male college students received 30 IU of intranasal oxytocin or placebo and were then recorded during exposure to a contagious yawning video stimulus. Contrary to the empathic modeling hypothesis, oxytocin did not increase contagious yawning but rather appeared to modulate its expression in ways indicative of an enhanced awareness of the social stigma associated with this behavior. In particular, individuals in the oxytocin condition were more likely to conceal their yawns and less likely to display overt cues associated with the behavior. Follow-up research could explore how social context and affiliation with the target stimulus alter this response. PMID- 26375927 TI - Parallel sparse and dense information coding streams in the electrosensory midbrain. AB - Efficient processing of incoming sensory information is critical for an organism's survival. It has been widely observed across systems and species that the representation of sensory information changes across successive brain areas. Indeed, peripheral sensory neurons tend to respond densely to a broad range of sensory stimuli while more central neurons tend to instead respond sparsely to a narrow range of stimuli. Such a transition might be advantageous as sparse neural codes are thought to be metabolically efficient and optimize coding efficiency. Here we investigated whether the neural code transitions from dense to sparse within the midbrain Torus semicircularis (TS) of weakly electric fish. Confirming previous results, we found both dense and sparse coding neurons. However, subsequent histological classification revealed that most dense neurons projected to higher brain areas. Our results thus provide strong evidence against the hypothesis that the neural code transitions from dense to sparse in the electrosensory system. Rather, they support the alternative hypothesis that higher brain areas receive parallel streams of dense and sparse coded information from the electrosensory midbrain. We discuss the implications and possible advantages of such a coding strategy and argue that it is a general feature of sensory processing. PMID- 26375929 TI - Abnormally increased surface expression of AMPA receptors in the cerebellum, cortex and striatum of Cln3(-/-) mice. AB - Mutations in the CLN3 gene cause a fatal neurodegenerative disorder, juvenile CLN3 disease. Exploring the cause of the motor coordination deficit in the Cln3( /-) mouse model of the disease we have previously found that attenuation of AMPA receptor activity in 1-month-old Cln3(-/-) mice significantly improves their motor coordination [20]. To elucidate the mechanism of the abnormally increased AMPA receptor function in Cln3(-/-) mice, we examined the surface expression of AMPA receptors using surface cross-linking in brain slices from 1-month-old wild type (WT) and Cln3(-/-) mice. In surface cross-linked brain samples, Western blotting for AMPA receptor subunits revealed significantly increased surface levels of GluA1 and GluA2 in the cerebellum, and of GluA2 in the cortex and striatum of Cln3(-/-) mice as compared to WT mice. Expression levels of the GluA4 subunit were similar in the cerebellum of WT and Cln3(-/-) mice. While intracellular GluA1 levels in the WT and Cln3(-/-) cerebellum or cortex were similar, the intracellular expression of GluA1 in the Cln3(-/-) striatum was decreased to 56% of the WT level. Our results show a prominent increase in AMPA receptor surface expression in the brain of Cln3(-/-) mice and suggest that CLN3 is involved in the regulation of AMPA receptor surface expression. PMID- 26375930 TI - Otolaryngologic surgery in children with trisomy 18 and 13. AB - OBJECTIVES: Trisomy 18 and 13 are the most common autosomal trisomy disorders after Down syndrome. Given the high mortality rate (5-10% one-year survival), trisomy 18 and 13 were historically characterized as uniformly lethal and palliation was the predominant management approach. Management strategy has shifted with recognition that through medical and surgical intervention, children with trisomy 18 and 13 can achieve developmental milestones, live meaningful lives, and exhibit long-term survival. Otolaryngologic surgery in children with trisomy 18 and 13 has not been described. The objective of this article is to describe the role of the otolaryngologist in the management of children with trisomy 18 and 13. METHODS AND MATERIALS: Retrospective cohort analysis of the surgery registry for the Support Organization for Trisomy 18, 13 and Related Disorders for otolaryngologic surgeries reported from 1988 through June 1, 2014. RESULTS: In the database of approximately 1349 children, 1380 procedures were reported, 231 (17%) of which were otolaryngologic. The most common otolaryngologic procedures were tympanostomy tube placement (57/231, 25%), cleft lip repair (40/231, 17%), tracheostomy (38/231, 16.5%), tonsillectomy and/or adenoidectomy (37/231, 16%), and cleft palate repair (30/231, 13%). Of the ten most common procedures reported, four were otolaryngologic. CONCLUSIONS: Seventeen percent of procedures performed in children with trisomy 18 and 13 were otolaryngologic, highlighting the significant role of the otolaryngologist in the treatment of these patients. Surgical intervention may be considered as part of a balanced approach to patient care. PMID- 26375931 TI - Teaching the pharyngeal flap and sphincter pharyngoplasty: The sticky note method. AB - OBJECTIVE: To demonstrate a cost-effective, quick, and easily reproducible three dimensional sticky note model to enhance the understanding and conceptualization of the geometry and steps of the pharyngeal flap and sphincter pharyngoplasty. METHODS: The method involves making specified incisions and rearrangements of readily available components, including disposable clear plastic cups, yellow and pink sticky notes, and white paper. Once assembly is complete, further incisions and remodeling are performed to simulate a pharyngeal flap or sphincter pharyngoplasty. RESULTS: The cost of the materials to make one model was $0.94. Average construction time was less than 10 min. CONCLUSION: This three dimensional model is an efficient, interactive, and simple visual aid to teach surgical trainees the geometry and steps of the pharyngeal flap and sphincter pharyngoplasty. PMID- 26375933 TI - Dimension and Complexity in Human Movement and Posture. AB - There has been considerable effort over the last 25 years to understand the emergence of complexity in motor output and how this relates to properties of the individual (e.g., age, disease state, etc.), environment (e.g., information) and task (e.g., movement, posture, isometric force). This paper addresses the behavioral dimension of motor complexity in movement and posture from a degrees of freedom (DF) perspective together with the change of complexity through aging, disease and fatigue. The dimension of behavior for a given perceptual-motor output is shown to be relatively low, dependent on the interaction between the individual, environmental, and task constraints and varies within a limited adaptive range for a given motor task. The determination of dimension in movement and posture has taken us beyond the traditional motor performance scores of behavior but it is not a sufficient characterization of the adaptive and emergent processes of complexity. PMID- 26375934 TI - What Can Biosignal Entropy Tell Us About Health and Disease? Applications in Some Clinical Fields. AB - Many physiological systems are paradigmatic examples of complex networks, displaying behaviors best studied by means of tools derived from nonlinear dynamics and fractal geometry. Furthermore, while conventional wisdom considers health as an 'orderly' situation (and diseases are often called 'disorders'), truth is that health is characterized by a remarkable (pseudo)-randomness, and the loss of this pseudo-randomness (i.e., the 'decomplex-ification' of the system's output) is one of the earliest signs of the system's dysfunction. The potential clinical uses of this information are evident. However, the instruments used to assess complexity are still under debate, and these tools are just beginning to find their place at the bedside. We present a brief overview of the potential uses of complexity analysis in several areas of clinical medicine. We comment on the metrics most frequently used, and we review specifically their application on certain neurologic diseases, aging, diabetes, febrile diseases and the critically ill patient. PMID- 26375935 TI - Differential Diagnosis: Shape and Function, Fractal Tools in the Pathology Lab. AB - Fractal analysis is a useful objective tool in describing complexity of shapes and signals providing information for understanding pathological changes. We present fractal approaches and software used in our pathology laboratory to analyze shapes of tumors in tissues and cells, to evaluate the microvessel network complexity in hereditary diseases or the complexity of the surface of blood cells in atherosclerosis-linked condition, as well to analyze function in vasculopathic subjects by chaotic analysis of electrocardiographic signals, in order to perform differential diagnosis. The fractal parameters appear to converge towards distinct values in pathological conditions compared to healthy, approaching the characteristics values of a percolation process or the diffusion limited aggregation process, respectively: a bifurcation that allows to support the diagnostic process of the pathologist in his daily work. These methods, presented here as a kind of a cookbook ready for the pathologist, are low cost and not time consuming. PMID- 26375936 TI - Different Faces of Variability in the Adaptive Process of Motor Skill Learning. AB - This study investigated the variability by considering an action programme as hierarchically organized, which reconciles invariant and variant features of motor skills at the macro- and microstructural level of analysis. It was assumed that invariant aspects of skilled actions express the macrostructure and therefore measures of sequencing, relative size, relative timing, relative force and relative pause time. The microstructure was related to the variant aspects so that total size, total movement time, total force, and total pause time were selected as its measures. These propositions were tested in an experimental design comprised by three learning phases: a stabilisation phase that entailed a given number of trials to achieve the functional stabilization on a graphic task, followed by transfer and retention phases. In the transfer phase, the graphic task was modified to yield different demands upon skill reorganization. Two such modifications demanded parametric changes (i.e. microstructure changes), in which graphic size and drawing speed were altered. Another modification demanded structural alterations (i.e. macrostructure change), in which drawing was changed. Overall, results supported the main predictions by showing that parametric changes in the task affected the microstructure, but did not affect the macrostructure consistently. Furthermore, a structural change affected both macro- and microstructure. PMID- 26375932 TI - Complex Adaptive Behavior and Dexterous Action. AB - Dexterous action, as conceptualized by Bernstein in his influential ecological analysis of human behavior, is revealed in the ability to flexibly generate behaviors that are adaptively tailored to the demands of the context in which they are embedded. Conceived as complex adaptive behavior, dexterity depends upon the qualities of robustness and degeneracy, and is supported by the functional complexity of the agent-environment system. Using Bernstein's and Gibson's ecological analyses of behavior situated in natural environments as conceptual touchstones, we consider the hypothesis that complex adaptive behavior capitalizes upon general principles of self-organization. Here, we outline a perspective in which the complex interactivity of nervous-system, body, and environment is revealed as an essential resource for adaptive behavior. From this perspective, we consider the implications for interpreting the functionality and dysfunctionality of human behavior. This paper demonstrates that, optimal variability, the topic of this special issue, is a logical consequence of interpreting the functionality of human behavior as complex adaptive behavior. PMID- 26375937 TI - Training the Antifragile Athlete: A Preliminary Analysis of Neuromuscular Training Effects on Muscle Activation Dynamics. AB - Athletic injuries typically occur when the stable, emergent coordination between behavioral processes breaks down due to external noise, or variability. A physiological system that operates at an optimal point on a spectrum of rigidity and flexibility may be better prepared to handle extreme external variability, and the purpose of the current experiment was to examine whether targeted neuromuscular training resulted in changes to the rigidity and flexibility of the gluteal muscle tonus signal as measured with electromyography prior to the landing phase of a drop vertical jump task. 10 adolescent female athletes who participated in a targeted 10-week neuromuscular training program and 6 controls participated, and their tonus dynamics were examined with recurrence quantification analysis prior to training and after the 10-week program. The dependent measures, percent laminarity (%LAM) and percent determinism (%DET) were hypothesized to decrease following training, and were submitted to a one tailed mixed-model ANOVA. The training group exhibited a decrease in %LAM and %DET after training compared to pre-training and controls. The present findings indicate increased metaflexibility (i.e., greater intermittency and an increase in internal randomness) in tonus dynamics following neuromuscular training, and have important implications for the prevention of musculoskeletal injury in sport, specifically within the context of external noise and antifragility. PMID- 26375938 TI - The Complexity of the Psychological Self and the Principle of Optimum Variability. AB - Linville's theory of self-complexity relies of concepts of information measurement to produce its core measurement of complexity, which is in turn thought to be positively correlated with indicators of psychological well-being. Empirical research, however, has not supported this assertion as it was initially intended. Research with complex adaptive systems, however, shows that self organized systems generally display mid-range values, whereas low-range values denote stereotypic, rigid, and possibly maladaptive behavior. High-range values, furthermore, tend to reflect disordered systems that could be maladaptive for other reasons. As a result, the linear correlations between metrics of complexity of the self and psychological well-being that were widely assumed in the empirical research are not appropriate. The substantive theory of self complexity, however, is not inconsistent with expectations from complex adaptive systems. Recommendations are given here to improve the data analysis and interpretation of empirical results currently on record concerning the complexity of the self and mental health outcomes. PMID- 26375939 TI - Healthy Variability in Organizational Behavior: Empirical Evidence and New Steps for Future Research. AB - The healthy variability thesis suggests that healthy systems function in a complex manner over time. This thesis is well-established in fields like physiology. In the field of organizational behavior, however, this relation is only starting to be explored. The objective of this article is threefold: First, we aim to provide a comprehensive review of the healthy variability thesis including some of the most important findings across different fields, with a focus on evidences from organizational research in work motivation and performance. Second, we discuss an opposite pattern, unhealthy stability, i.e., the relationship between unhealthy behaviors and lower variability. Again, we provide evidence from diverse areas, from affective processes to disruptive organizational comportments like mobbing. Third, we provide a critical evaluation of current methodological trends and highlight what we believe to be the main factors that are stopping organizational research from advancing in the field. Theoretical, methodological and epistemological implications are discussed. To conclude, we draw a compilation of the lessons learned, which hopefully provide insights for prolific research avenues. Our main purpose is to raise awareness of the healthy variability thesis and to enthuse organizational researchers to consider it in order to advance existing knowledge, revisit old theories and create new ones. PMID- 26375940 TI - What is Optimum Variability? AB - Guastello (2015a) opened the call for articles for this issue with Goldberger (1991) and colleagues' findings of chaotic variability in healthy heart rate, noting, 'the principle of healthy variability has extended to other biomedical and psychological phenomena.' He suggests a dialectical underpinning for optimal variability involving 'a combination of the minimum entropy or free energy principle that pushes in a downward direction, and Ashby's Law of Requisite Variety that pushes in an upward direction.' Each of the papers in this issue addresses optimal variability across a variety of health-related areas. The present article surveys these seven papers in relation to five conceptual questions about optimal variability: (a) Is variability a positive or a negative, and how are positive things related to health? (b) How shall we define and measure variability? (c) What constitutes an optimum, and how do we locate one? (d) What is the relationship between optimum variability and health? Finally, it touches on (e) What are underlying principles and phenomena behind healthy variability, and can they inform our vocabulary for health? The paper concludes by discussing practical approaches to dealing with optimization. PMID- 26375942 TI - Pharmacokinetic drug-drug interaction study between raltegravir and citalopram. AB - BACKGROUND: Depression is the most common mental health disorder among HIV infected patients. When treating HIV-infected patients with a selective serotonin reuptake inhibitor (SSRI), potential drug-drug interactions with antiretroviral agents have to be taken into account. We investigated the two-way pharmacokinetic drug-drug interaction and tolerability of concomitant administration of the SSRI citalopram and the HIV-1 integrase inhibitor raltegravir in healthy volunteers. METHODS: An open-label, crossover, two-period trial was conducted in 24 healthy volunteers. Subjects received the following treatments: citalopram 20 mg once daily for 2 weeks followed by the combination with raltegravir 400 mg twice daily for 5 days and after a washout period raltegravir 400 mg twice daily for 5 days. Intensive steady-state pharmacokinetic blood sampling was performed. Geometric mean ratios (GMRs) of the combination versus the reference treatment and 90% CIs were calculated for the area under the plasma concentration-time curve (AUC). CYP2C19 genotyping was performed because it influences N-demethylation of citalopram to desmethylcitalopram. RESULTS: A total of 22 healthy volunteers completed the trial. GMRs (90% CI) were 1.00 (0.98, 1.03) for citalopram AUC0-24 h, 0.99 (0.88, 1.12) for desmethylcitalopram AUC0-24 h and 0.77 (0.50, 1.19) for raltegravir AUC0-12 h. Raltegravir plasma concentration 12 h after intake (C12 h) did not change with concomitant use of citalopram. Within each CYP2C19 phenotype subgroup the citalopram metabolite-to-parent ratio, which is a measure for metabolic enzyme activity, was not influenced by concomitant raltegravir use. CONCLUSIONS: Raltegravir does not influence the pharmacokinetics of citalopram and desmethylcitalopram. Citalopram did not change the pharmacokinetics of raltegravir in a clinically meaningful way. The combination was well tolerated and can be administered without dose adjustments. ClinicalTrials.gov NCT01978782. PMID- 26375944 TI - Reclassification of Saccharomycodes sinensis, Proposal of Yueomyces sinensis gen. nov., comb. nov. within Saccharomycetaceae (Saccharomycetales, Saccharomycotina). AB - The phylogenetic position of Saccharomycodes sinensis has been debated by yeast taxonomists. In this study, a multigene phylogenetic analysis based on four regions, namely the 18S ribosomal DNA (rDNA), the D1/D2 domains of the 26S rDNA, the second largest subunit of RNA polymerase II gene (RPB2) and translation elongation factor 1-alpha gene (EF1-alpha), were performed to address the phylogenetic placement of S. sinensis. Our result indicated that S. sinensis belongs to Saccharomycetaceae instead of Saccharomycodaceae, and forms a single species lineage divergent from the other genera within Saccharomycetaceae. Yueomyces gen. nov. (MycoBank No. MB 811648) is proposed in the Saccharomycetaceae with Y. sinensis comb. nov. (MycoBank No. MB 811649, type strain CGMCC 2.01395T = IFO 10111T = CBS 7075T) as the type species. PMID- 26375945 TI - Patient-Oriented Research and Care. PMID- 26375946 TI - CareMore "Field Trip" Report. PMID- 26375943 TI - Uterine microvascular sensitivity to nanomaterial inhalation: An in vivo assessment. AB - With the tremendous number and diverse applications of engineered nanomaterials incorporated in daily human activity, exposure can no longer be solely confined to occupational exposures of healthy male models. Cardiovascular and endothelial cell dysfunction have been established using in vitro and in situ preparations, but the translation to intact in vivo models is limited. Intravital microscopy has been used extensively to understand microvascular physiology while maintaining in vivo neurogenic, humoral, and myogenic control. However, a tissue specific model to assess the influences of nanomaterial exposure on female reproductive health has not been fully elucidated. Female Sprague Dawley (SD) rats were exposed to nano-TiO2 aerosols (171 +/- 6 nm, 10.1 +/- 0.39 mg/m(3), 5h) 24-hours prior to experimentation, leading to a calculated deposition of 42.0 +/- 1.65 MUg. After verifying estrus status, vital signs were monitored and the right horn of the uterus was exteriorized, gently secured over an optical pedestal, and enclosed in a warmed tissue bath using intravital microscopy techniques. After equilibration, significantly higher leukocyte-endothelium interactions were recorded in the exposed group. Arteriolar responsiveness was assessed using ionophoretically applied agents: muscarinic agonist acetylcholine (0.025 M; ACh; 20, 40, 100, and 200 nA), and nitric oxide donor sodium nitroprusside (0.05 M; SNP; 20, 40, and 100 nA), or adrenergic agonist phenylephrine (0.05 M; PE; 20, 40, and 100 nA) using glass micropipettes. Passive diameter was established by tissue superfusion with 10(-4)M adenosine. Similar to male counterparts, female SD rats present systemic microvascular dysfunction; however the ramifications associated with female health and reproduction have yet to be elucidated. PMID- 26375947 TI - The Relationship Between Length of Surgery and the Incidence of Pressure Ulcers in Cardiovascular Surgical Patients: A Retrospective Study. AB - OBJECTIVE: The aim of this study was to investigate the relationship between the length of surgery and the incidence of pressure ulcers (PrUs) in cardiovascular surgical patients. METHODS: A retrospective analysis was performed among consecutive patients with cardiac surgery in 2012. Propensity score matching was used to control differences in the baseline characteristics between with and without surgery-related pressure ulcer (SRPU) groups. RESULTS: A total of 286 patients with cardiac surgery were included in the study: 47 patients developed 57 SRPUs, with incidence of 16.4% (95% confidence interval, 12.3%-21.2%); 97.9% of SRPUs were Stage I, and the other 2.1% were Stage II. After propensity score matching, statistically significant difference of the length of surgery between the 2 groups was found (195 minutes [30-330 minutes] vs 240 minutes [125-675 minutes], P = .003). However, the length of cardiopulmonary bypass was found to be not statistically significantly different between the 2 groups (37 minutes [15 144 minutes] vs 44 minutes [16-107 minutes], P = .830). The curve fitting showed the SRPU incidence increased gradually with the extension of length of surgery. CONCLUSIONS: The authors' retrospective analysis showed the length of surgery was an important risk factor for PrUs in cardiovascular surgical patients, but not the length of cardiopulmonary bypass. The incidence of SRPUs increased gradually with the extension of length of surgery. PMID- 26375948 TI - Being an Informal Caregiver of a Person with a Pressure Ulcer in the Azores Islands. AB - OBJECTIVE: This study aimed at both understanding the experience of informal caregivers of people with pressure ulcers (PrUs), as well as perceiving the relevant aspects of the narratives emerging from the experience of those caregivers. DESIGN: A qualitative, exploratory, grounded-based theory data analysis was implemented. The authors used NVivo 9 software (QSR International Inc, Burlington, Massachusetts) on semistructured interviews. PARTICIPANTS: The study participants were 9 informal caregivers of people with PrUs. RESULTS AND DISCUSSION: An individual's personal characteristics, the person he or she is caring for, and social pressure are typically the primary reasons to be a caregiver. In fact, PrUs require specific care associated with an impact on caregivers at different levels, including changes in everyday life, needs and feelings emerging from the care they provide, quality of life conditioned by their professional status, and burdens induced by physical and emotional demands. Oftentimes, family members and external entities--with emphasis on the nursing team--provide support to the caregiver. Caregivers show both satisfaction and dissatisfaction with the care provided, with the evolution of the PrU and with the support of external agents. CONCLUSION: The experience of informal caregivers of people with PrUs is based on 5 dimensions: (1) reasons to be caregivers, (2) care provided to the PrU, (3) impacts on the caregiver, (4) support to the caregiver, and (5) satisfaction or dissatisfaction of the caregiver. PMID- 26375949 TI - Pressure Ulcers in Older Adults: A Prevalence Study. AB - OBJECTIVE: The purpose of this study was to measure the prevalence of pressure ulcers (PrUs) in an older adult population. DESIGN: A cross-sectional study. SETTING: The study included all the individuals being cared for in the units of medicine, surgery, intensive care, and medical-surgical specialties of 47 hospitals, 57 public nursing homes, and 37 home care services. PARTICIPANTS: The authors' observational study included 11,957 patients older than 70 years. MAIN OUTCOME MEASURES: Of the population, 50.75% (6067) were assessed to be at risk of developing PrUs according to the Braden Scale, and 24.66% (2949) had already developed PrUs. In addition, a significant association was found between increased risk (Braden <16) and the presence of PrUs with an odds ratio (OR) of 8.71 (confidence interval [CI], 7.52-10.10) in high-risk subjects (Braden <= 12) and an OR of 3.86 (CI, 3.36-4.44) in very high-risk patients (Braden 13-16). In the survey, 84.6% of the subjects with PrUs were incontinent, and incontinence increased the risk of developing PrUs in the authors' sample (OR, 1.54; CI, 1.34 1.77). CONCLUSIONS: The authors' data reported in the literature show that the prevalence of PrUs increases as an individual ages. The authors gathered data that showed a large area of intervention in managing the prevention of PrUs, such as an adequate use of protective aids, correcting malnutrition, and controlling incontinence. These results suggest that clinicians should focus more on the prevention of PrUs in older adults. PMID- 26375950 TI - Optimizing the Moisture Management Tightrope with Wound Bed Preparation 2015(c). AB - PURPOSE: To provide an overview of moisture management and its importance in wound care. TARGET AUDIENCE: This continuing education activity is intended for physicians and nurses with an interest in skin and wound care. OBJECTIVES: After participating in this educational activity, the participant should be better able to:1. Summarize causes and treatments for moisture balance issues of chronic wounds.2. Recognize the properties of dressings used for treatment for moisture management of chronic wounds and antiseptic agent cytotoxicity.3. Explain study findings of the effectiveness of dressing choices for treatment of chronic wounds. OBJECTIVE: To provide an overview of moisture management and its importance in wound care. The authors evaluate the impact of moisture management for optimal wound care and assess current wound management strategies relating to antisepsis and moist wound healing utilizing the wound bed preparation paradigm 2015 update. The discussion distinguishes the form and function of wound care dressing classes available for optimal moisture management. CONCLUSION: Moisture management for chronic wounds is best achieved with modern moist interactive dressings if the wound has the ability to heal. PMID- 26375952 TI - The Strategic View of Meaningful Use: Part 1. PMID- 26375953 TI - The Diagnostic Value of Capillary Refill Time for Detecting Serious Illness in Children: A Systematic Review and Meta-Analysis. AB - IMPORTANCE: Capillary refill time (CRT) is widely recommended as part of the routine assessment of unwell children. OBJECTIVE: To determine the diagnostic value of capillary refill time for a range of serious outcomes in children. METHODS: We searched Medline, Embase and CINAHL from inception to June 2014. We included studies that measured both capillary refill time and a relevant clinical outcome such as mortality, dehydration, meningitis, or other serious illnesses in children aged up to 18 years of age. We screened 1,265 references, of which 24 papers were included in this review. Where sufficient studies were available, we conducted meta-analysis and constructed hierarchical summary ROC curves. RESULTS: Meta-analysis on the relationship between capillary refill time and mortality resulted in sensitivity of 34.6% (95% CI 23.9 to 47.1%), specificity 92.3% (88.6 to 94.8%), positive likelihood ratio 4.49 (3.06 to 6.57), and negative likelihood ratio 0.71 (0.60 to 0.84). Studies of children attending Emergency Departments with vomiting and diarrhea showed that capillary refill time had specificity of 89 to 94% for identifying 5% dehydration, but sensitivity ranged from 0 to 94%. This level of heterogeneity precluded formal meta-analysis of this outcome. Meta analysis was not possible for other outcomes due to insufficient data, but we found consistently high specificity for a range of outcomes including meningitis, sepsis, admission to hospital, hypoxia, severity of illness and dengue. CONCLUSIONS: Our results show that capillary refill time is a specific sign, indicating that it can be used as a "red-flag": children with prolonged capillary refill time have a four-fold risk of dying compared to children with normal capillary refill time. The low sensitivity means that a normal capillary refill time should not reassure clinicians. PMID- 26375955 TI - Intralymphatic Histiocytosis: A case report and review of literature. PMID- 26375954 TI - Transforming Growth Factor Beta (TGF-beta) Is a Muscle Biomarker of Disease Progression in ALS and Correlates with Smad Expression. AB - We recently identified Smads1, 5 and 8 as muscle biomarkers in human ALS. In the ALS mouse, these markers are elevated and track disease progression. Smads are signal transducers and become activated upon receptor engagement of ligands from the TGF-beta superfamily. Here, we sought to characterize ligands linked to activation of Smads in ALS muscle and their role as biomarkers of disease progression. RNA sequencing data of ALS muscle samples were mined for TGF-beta superfamily ligands. Candidate targets were validated by qRT-PCR in a large cohort of human ALS muscle biopsy samples and in the G93A SOD1 mouse. Protein expression was evaluated by Western blot, ELISA and immunohistochemistry. C2C12 muscle cells were used to assess Smad activation and induction. TGF-beta1, 2 and 3 mRNAs were increased in ALS muscle samples compared to controls and correlated with muscle strength and Smads1, 2, 5 and 8. In the G93A SOD1 mouse, the temporal pattern of TGF-beta expression paralleled the Smads and increased with disease progression. TGF-beta1 immunoreactivity was detected in mononuclear cells surrounding muscle fibers in ALS samples. In muscle cells, TGF-beta ligands were capable of activating Smads. In conclusion, TGF-beta1, 2 and 3 are novel biomarkers of ALS in skeletal muscle. Their correlation with weakness in human ALS and their progressive increase with advancing disease in the ALS mouse suggest that they, as with the Smads, can track disease progression. These ligands are capable of upregulating and activating Smads and thus may contribute to the Smad signaling pathway in ALS muscle. PMID- 26375958 TI - Correction: An Analysis of Overstory Tree Canopy Cover in Sites Occupied by Native and Introduced Cottontails in the Northeastern United States with Recommendations for Habitat Management for New England Cottontail. PMID- 26375957 TI - Human Cardiac Progenitor Spheroids Exhibit Enhanced Engraftment Potential. AB - A major obstacle to an effective myocardium stem cell therapy has always been the delivery and survival of implanted stem cells in the heart. Better engraftment can be achieved if cells are administered as cell aggregates, which maintain their extra-cellular matrix (ECM). We have generated spheroid aggregates in less than 24 h by seeding human cardiac progenitor cells (hCPCs) onto methylcellulose hydrogel-coated microwells. Cells within spheroids maintained the expression of stemness/mesenchymal and ECM markers, growth factors and their cognate receptors, cardiac commitment factors, and metalloproteases, as detected by immunofluorescence, q-RT-PCR and immunoarray, and expressed a higher, but regulated, telomerase activity. Compared to cells in monolayers, 3D spheroids secreted also bFGF and showed MMP2 activity. When spheroids were seeded on culture plates, the cells quickly migrated, displaying an increased wound healing ability with or without pharmacological modulation, and reached confluence at a higher rate than cells from conventional monolayers. When spheroids were injected in the heart wall of healthy mice, some cells migrated from the spheroids, engrafted, and remained detectable for at least 1 week after transplantation, while, when the same amount of cells was injected as suspension, no cells were detectable three days after injection. Cells from spheroids displayed the same engraftment capability when they were injected in cardiotoxin-injured myocardium. Our study shows that spherical in vivo ready-to-implant scaffold-less aggregates of hCPCs able to engraft also in the hostile environment of an injured myocardium can be produced with an economic, easy and fast protocol. PMID- 26375959 TI - Nanoscale Imaging of Local Few-Femtosecond Near-Field Dynamics within a Single Plasmonic Nanoantenna. AB - The local enhancement of few-cycle laser pulses by plasmonic nanostructures opens up for spatiotemporal control of optical interactions on a nanometer and few femtosecond scale. However, spatially resolved characterization of few-cycle plasmon dynamics poses a major challenge due to the extreme length and time scales involved. In this Letter, we experimentally demonstrate local variations in the dynamics during the few strongest cycles of plasmon-enhanced fields within individual rice-shaped silver nanoparticles. This was done using 5.5 fs laser pulses in an interferometric time-resolved photoemission electron microscopy setup. The experiments are supported by finite-difference time-domain simulations of similar silver structures. The observed differences in the field dynamics across a single particle do not reflect differences in plasmon resonance frequency or dephasing time. They instead arise from a combination of retardation effects and the coherent superposition between multiple plasmon modes of the particle, inherent to a few-cycle pulse excitation. The ability to detect and predict local variations in the few-femtosecond time evolution of multimode coherent plasmon excitations in rationally synthesized nanoparticles can be used in the tailoring of nanostructures for ultrafast and nonlinear plasmonics. PMID- 26375961 TI - Give me a better break: Choosing workday break activities to maximize resource recovery. AB - Surprisingly little research investigates employee breaks at work, and even less research provides prescriptive suggestions for better workday breaks in terms of when, where, and how break activities are most beneficial. Based on the effort recovery model and using experience sampling methodology, we examined the characteristics of employee workday breaks with 95 employees across 5 workdays. In addition, we examined resources as a mediator between break characteristics and well-being. Multilevel analysis results indicated that activities that were preferred and earlier in the work shift related to more resource recovery following the break. We also found that resources mediated the influence of preferred break activities and time of break on health symptoms and that resource recovery benefited person-level outcomes of emotional exhaustion, job satisfaction, and organizational citizenship behavior. Finally, break length interacted with the number of breaks per day such that longer breaks and frequent short breaks were associated with more resources than infrequent short breaks. PMID- 26375962 TI - Are anxious workers less productive workers? It depends on the quality of social exchange. AB - In this article, we draw from Conservation of Resources Theory to advance and test a framework which predicts that emotional exhaustion plays an explanatory role underlying the relation between workplace anxiety and job performance. Further, we draw from social exchange theories to predict that leader-member exchange and coworker exchange will mitigate the harmful effects of anxiety on job performance. Findings across a 3-wave study of police officers supported our model. Emotional exhaustion mediated the link between workplace anxiety and job performance, over and above the effect of cognitive interference. Further, coworker exchange mitigated the positive relation between anxiety and emotional exhaustion, while leader-member exchange mitigated the negative relation between emotional exhaustion and job performance. This study elucidates the effects of workplace anxiety on resource depletion via emotional exhaustion and highlights the value of drawing on social resources to offset the potentially harmful effects of workplace anxiety on job performance. PMID- 26375960 TI - A Single Oral Administration of Theaflavins Increases Energy Expenditure and the Expression of Metabolic Genes. AB - Theaflavins are polyphenols found in black tea, whose physiological activities are not well understood. This study on mice evaluated the influence of a single oral administration of theaflavins on energy metabolism by monitoring the initial metabolic changess in skeletal muscle and brown adipose tissue (BAT). Oxygen consumption (VO2) and energy expenditure (EE) were increased significantly in mice treated with theaflavin rich fraction (TF) compared with the group administered vehicle alone. There was no difference in locomotor activity. Fasting mice were euthanized under anesthesia before and 2 and 5, 20-hr after treatment with TF or vehicle. The mRNA levels of uncoupling protein-1 (UCP-1) and peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) in BAT were increased significantly 2-hr after administration ofTF. The levels of UCP-3 and PGC-1alpha in the gastrocnemius muscle were increased significantly 2 and 5-hr after administration of TF. The concentration of phosphorylated AMP activated protein kinase (AMPK) 1alpha was also increased significantly in the gastrocnemius 2 and 5-hr after treatment with TF. These results indicate that TF significantly enhances systemic energy expenditure, as evidenced by an increase in expression of metabolic genes. PMID- 26375963 TI - Development of an in Silico Profiler for Mitochondrial Toxicity. AB - This study outlines the analysis of mitochondrial toxicity for a variety of pharmaceutical drugs extracted from Zhang et al. ((2009) Toxicol. In Vitro, 23, 134-140). These chemicals were grouped into categories based upon structural similarity. Subsequently, mechanistic analysis was undertaken for each category to identify the molecular initiating event driving mitochondrial toxicity. The mechanistic information elucidated during the analysis enabled mechanism-based structural alerts to be developed and combined together to form an in silico profiler. This profiler is envisaged to be used to develop chemical categories based upon similar mechanisms as part of the adverse outcome pathway paradigm. Additionally, the profiler could be utilized in screening large data sets in order to identify chemicals with the potential to induce mitochondrial toxicity. PMID- 26375964 TI - Early detection of parenting and developmental problems in toddlers: A randomized trial of home visits versus well-baby clinic visits in the Netherlands. AB - OBJECTIVE: The early detection of parenting and developmental problems by preventive child health care (CHC) services in the Netherlands takes place almost exclusively at the well-baby clinic. This study assesses whether, compared to a visit to the well-baby clinic, a home visit improves early detection. METHODS: 4481 eligible 18-month-old children and their parents were randomized to either a visit to the well-baby clinic or a home visit in the period from December 2006 to January 2008. A CHC nurse held structured interviews using the validated Structured Problem Analysis of Raising Kids (SPARK). Differences in the percentage of children with high or increased risks of parenting and developmental problems as assessed by the SPARK were analyzed with ordinal regression. Secondary outcomes included the percentage of parents attending, parents' concerns, needs assessment by parents and CHC professionals and user experience. RESULTS: Response rates were 94.0% for the home visit group and 93.2% for the well-baby clinic group. Using the SPARK at home identified significantly more high-risk children compared to clinic visits (3.7 vs. 2.6%) and fewer children with increased risk (19.1 vs. 20.7%; overall p=0.028). Home visits more often involved both parents and other children. At home, parents reported more concerns. Both parents and CHC nurses more often expressed the need for support and reported significantly better experiences at home. CONCLUSIONS: Aided by a validated structured interview, CHC professionals detect more children with high risks of parenting and child-developmental problems during home visits than during clinic visits. CLINICAL TRIAL REGISTRATION: www.trialregister.nl Identifier: NTR1413. PMID- 26375965 TI - A systematic review of SNAPO (Smoking, Nutrition, Alcohol, Physical activity and Obesity) randomized controlled trials in young adult men. AB - OBJECTIVES: To investigate the effectiveness of Smoking, Nutrition, Alcohol, Physical activity and Obesity (SNAPO) interventions in young men exclusively. The secondary aim was to evaluate the recruitment, retention and engagement strategies. METHODS: A search with no date restrictions was conducted across seven databases. Randomized controlled trials recruiting young men only (aged 18 35 years) into interventions targeting any SNAPO risk factors were included. RESULTS: Ten studies were included (two nutrition, six alcohol use, two targeting multiple SNAPO risk factors). Six studies (two nutrition, three alcohol use and one targeting multiple SNAPO risk factors) demonstrated significant positive short-term intervention effects, but impact was either not assessed beyond the intervention (n=3), had short-term follow-up (<=6 months) (n=2) or not sustained beyond six months (n=1). Overall, a high risk of bias was identified across studies. Only one study undertook a power calculation and recruited the required sample size. Adequate retention was achieved in three studies. Effectiveness of engagement strategies was not reported in any studies. CONCLUSIONS: Despite preliminary evidence of short-term effectiveness of SNAPO interventions in young men, few studies characterized by a high risk of bias were identified. High quality SNAPO interventions for young men are warranted. PMID- 26375966 TI - Co-occurrence of chronic disease lifestyle risk factors in middle-aged and older immigrants: A cross-sectional analysis of 264,102 Australians. AB - BACKGROUND: The way in which lifestyle risk factors for chronic disease co-occur among people with different cultural backgrounds is largely unknown. METHODS: This study investigated chronic disease risk among immigrants aged >=45 years in Australia by combining common lifestyle risk factors into a weighted chronic disease risk index (CDRI). Among 64,194 immigrants and 199,908 Australian-born participants in the 45 and Up Study (2006-2009), Poisson regression was used to derive relative risks (RR) and 95% confidence intervals (CI) for five risk factors (smoking, alcohol use, overweight/obesity, physical activity, diet) by place of birth adjusting for socio-demographic characteristics. Multiple linear regression was used to determine adjusted mean differences (AMDs) in CDRI score by place of birth and years lived in Australia. RESULTS: Immigrants had higher RRs of smoking than Australian-born participants, lower RRs of excessive alcohol consumption and overweight/obesity, and no difference in RR for physical inactivity and insufficient fruit/vegetable intake. Participants born in the Middle East/North Africa (AMD 3.5, 95% CI 2.7, 4.3), Eastern/Central Europe (1.3, 0.8, 1.9), and Western Europe (0.5, 0.1, 0.8) had higher mean CDRI scores than Australian-born participants, while participants born in East Asia (-7.2, -7.8, 6.6), Southeast Asia (-6.6, -7.2, -6.1), Central/South Asia (-3.1, -4.0, -2.1), Sub-Saharan Africa (-1.9, -2.6, -1.2) and the United Kingdom/Ireland (-0.2, -0.5, 0.0) had lower scores. CDRI score among immigrants generally approximated that of Australian-born participants with greater years lived in Australia. CONCLUSIONS: This study reveals differences in potential risk of chronic disease among different immigrant groups in Australia. PMID- 26375967 TI - Sound Source Localization and Speech Understanding in Complex Listening Environments by Single-sided Deaf Listeners After Cochlear Implantation. AB - OBJECTIVE: To assess improvements in sound source localization and speech understanding in complex listening environments after unilateral cochlear implantation for single-sided deafness (SSD). STUDY DESIGN: Nonrandomized, open, prospective case series. SETTING: Tertiary referral center. PATIENTS: Nine subjects with a unilateral cochlear implant (CI) for SSD (SSD-CI) were tested. Reference groups for the task of sound source localization included young (n = 45) and older (n = 12) normal-hearing (NH) subjects and 27 bilateral CI (BCI) subjects. INTERVENTION: Unilateral cochlear implantation. MAIN OUTCOME MEASURES: Sound source localization was tested with 13 loudspeakers in a 180 arc in front of the subject. Speech understanding was tested with the subject seated in an 8 loudspeaker sound system arrayed in a 360-degree pattern. Directionally appropriate noise, originally recorded in a restaurant, was played from each loudspeaker. Speech understanding in noise was tested using the Azbio sentence test and sound source localization quantified using root mean square error. RESULTS: All CI subjects showed poorer-than-normal sound source localization. SSD CI subjects showed a bimodal distribution of scores: six subjects had scores near the mean of those obtained by BCI subjects, whereas three had scores just outside the 95th percentile of NH listeners. Speech understanding improved significantly in the restaurant environment when the signal was presented to the side of the CI. CONCLUSION: Cochlear implantation for SSD can offer improved speech understanding in complex listening environments and improved sound source localization in both children and adults. On tasks of sound source localization, SSD-CI patients typically perform as well as BCI patients and, in some cases, achieve scores at the upper boundary of normal performance. PMID- 26375968 TI - Pitch Discrimination: An Independent Factor in Cochlear Implant Performance Outcomes. AB - OBJECTIVE: To assess differences in pitch-ranking ability across a range of speech understanding performance levels and as a function of electrode position. STUDY DESIGN: An observational study of a cross-section of cochlear implantees. SETTING: Tertiary referral center for cochlear implantation. PATIENTS: A total of 22 patients were recruited. All three manufacturers' devices were included (MED EL, Innsbruck, Austria, n = 10; Advanced Bionics, California, USA, n = 8; and Cochlear, Sydney, Australia, n = 4) and all patients were long-term users (more than 18 months). Twelve of these were poor performers (scores on BKB sentence lists <60%) and 10 were excellent performers (BKB >90%). INTERVENTION: After measurement of threshold and comfort levels, and loudness balancing across the array, all patients underwent thorough pitch-ranking assessments at 80% of comfort levels. MAIN OUTCOME MEASURE: Ability to discriminate pitch across the electrode array, measured by consistency in discrimination of adjacent pairs of electrodes, as well as an assessment of the pitch order across the array using the midpoint comparison task. RESULTS: Within the poor performing group there was wide variability in ability to pitch rank, from no errors, to a complete inability to reliably and consistently differentiate pitch change across the electrode array. Good performers were overall significantly more accurate at pitch ranking (p = 0.026). Consistent pitch ranking was found to be a significant independent predictor of BKB score, even after adjusting for age. Users of the MED-EL implant experienced significantly more pitch confusions at the apex than at more basal parts of the electrode array. CONCLUSIONS: Many cochlear implant users struggle to discriminate pitch effectively. Accurate pitch ranking appears to be an independent predictor of overall outcome. Future work will concentrate on manipulating maps based upon pitch discrimination findings in an attempt to improve speech understanding. PMID- 26375969 TI - Impact of Perioperative Oral Steroid Use on Low-frequency Hearing Preservation After Cochlear Implantation. AB - OBJECTIVE: To investigate the efficacy of a perioperative oral steroid taper on low-frequency hearing preservation after cochlear implantation. STUDY DESIGN: Retrospective case series. SETTING: Tertiary referral center. PATIENTS: Consecutive cochlear implant recipients between January 2012 and December 2014 who were candidates for a hearing preservation approach based on preoperative pure tone thresholds were identified. INTERVENTIONS: A subgroup of patients received a 2-week oral corticosteroid taper beginning 3 days before surgery. All patients were implanted using standard length electrodes. MAIN OUTCOME MEASURES: The preservation of low-frequency pure tone thresholds on the first postoperative audiogram was assessed. Secondary outcome measures included the respective impacts of age, diabetes, and electrode array type on hearing preservation, the durability of hearing preservation over time, and the development of medical complications related to steroid use. RESULTS: Twenty-seven ears met inclusion criterion, and the mean age at implantation was 49.8 years (median 62 yr, range 2 81 yr). Twenty patients (74.1%, mean age 48.7 yr) received an oral corticosteroid taper, whereas 7 (25.9%, mean age 53.1 yr) did not. The rate (p < 0.01) and degree (p < 0.01) of hearing preservation as measured at implant activation was greater for patients who received an oral steroid taper than those who did not. There were no medical complications related to steroid use. CONCLUSION: A 2-week oral prednisone taper beginning before surgery may positively affect the incidence and degree of low-frequency hearing preservation after cochlear implantation. PMID- 26375970 TI - Measurement of Cochlear Implant Electrode Position From Intraoperative Post insertion Skull Radiographs: A Validation Study. AB - OBJECTIVE: To validate a method of measuring angular depth of insertion (aDOI) as well as positional depth of each electrode contact in a cochlear implant by using intraoperative postinsertion skull radiographs. STUDY DESIGN: Retrospective review. SETTING: Tertiary referral center. PATIENTS: Intraoperative postinsertion radiographs obtained from 18 cochlear implant recipients were chosen for analysis. One high-resolution computer tomography scan of the head with the electrode in place was also analyzed. One cadaveric temporal bone with an inserted electrode provided additional data for analysis. INTERVENTION: aDOI and position of each electrode contact were measured from the radiographs using readily available software. High-resolution computer tomography imaging of the cochlea and electrode were reconstructed in three dimensions and used to simulate head rotation during intraoperative radiographs. The cadaveric temporal bone was imaged by x-ray at various acquisition angles. MAIN OUTCOME MEASURES: We evaluated the error introduced in measuring aDOI by assessing intra- and inter rater variability. We also evaluated the error introduced by x-ray acquisition at nonstandardized angles by analyzing the three-dimensional construct and the cadaveric temporal bone. RESULTS: The concordance correlation coefficients for intrarater (0.991) and inter-rater (0.996) variability in aDOI measurement were excellent. The error introduced by nonstandardized x-ray acquisition angles was only -12.5 degrees to +15.8 degrees even at the limits of clinically relevant head rotation. CONCLUSIONS: The intraoperative postinsertion radiograph is sufficient for estimating positional depth of electrode contacts and the aDOI. This measure is robust in the face of nonstandardized x-ray acquisition angles, and shows good intra- and inter-rater variability. PMID- 26375971 TI - Malignant Otitis Externa: A Novel Stratification Protocol for Predicting Treatment Outcomes. AB - OBJECTIVES: 1) Stratify malignant otitis externa into severe and nonsevere disease categories. 2) Predict treatment courses and outcomes based on this stratification. SETTING: Tertiary center. PATIENTS: Retrospective review 2004 to 2014; 28 patients. Inclusion criteria are a diagnosis by senior authors, radiographic evidence of disease, admission for intravenous antibiotics/debridement, minimum 1 year of follow-up. INTERVENTIONS: Severe group stratification if two or more of the following: cranial nerve VII palsy, fungal positive culture, relapse, surgery performed, major radiographic findings. All other patients stratified to nonsevere group. MAIN OUTCOME MEASURES: Cure, alive/refractory disease, death by disease, death by other cause. Secondary measures are antibiotic duration and number of disease-related admissions. RESULTS: Forty-three percent (12 of 28) and 57% (16 of 28) of patients stratified into the severe and nonsevere groups. The severe group had significantly more adverse disease-specific outcomes than the nonsevere group (7 of 12 versus 0 of 16; p = 0.002). Disease-specific mortality was 42% and 0% in the severe and nonsevere groups, respectively. The severe group had longer antibiotic courses (12.8 versus 6.9 wk; p = 0.01) and more disease-related admissions/relapses (1.6 versus 1, p < 0.001). Only four of 12 severe group patients achieved cure. All but two nonsevere patients achieved cure, with those two dying of other causes. CONCLUSION: A subgroup of malignant otitis externa may exist that is not as susceptible to parenteral antibiotics and local debridement. A combination of clinical and radiographic findings may be useful for stratifying patients into severe/nonsevere categories. Patients with severe disease may be more likely to die of their disease and have worse treatment courses such that additional surgical intervention may be indicated. PMID- 26375972 TI - Does Checking the Placement of Ossicular Prostheses via the Posterior Tympanotomy Improve Hearing Results After Cholesteatoma Surgery? AB - INTRODUCTION: Posterior tympanotomy (PT) is often performed during the surgical management of middle ear cholesteatoma with extension in the retrotympanum area. This PT can also be used to control the right position of the ossicular prosthesis masked by the tympanic membrane reconstruction. OBJECTIVE: To compare audiologic results after ossiculoplasty performed via the outer ear canal and via the PT for patients with cholesteatoma. MATERIALS AND METHODS: Retrospective chart reviews were performed for 68 patients (68 ears) with cholesteatoma who underwent titanium ossicular prosthesis surgery between January 2007 and January 2011. We compared audiologic results between two groups: the WPT group (the group without checking the prosthesis via the PT) and the PT group (the group with placing and/or checking the prosthesis via the PT). A postoperative pure-tone average air-bone gap of 20 dB or less was considered a successful hearing result. RESULTS: Of the patients who underwent canal wall-up mastoidectomy for cholesteatoma with ossicular chain reconstruction by titanium prosthesis, 36 patients (20 total ossicular replacement prosthesis [TORP], 16 partial ossicular replacement prosthesis [PORP]) were in the PT group and 32 patients (16 TORP, 16 PORP) were in the WPT group. The global success rate (defined as a mean residual air-bone gap < 20 dB) was 50% in the WPT group (56% in the subgroup PORP, 44% in the subgroup TORP) and 42% in the PT group (62% in PORP, 25% in TORP). There was no case with extrusion of the prosthesis in either group. No facial palsy occurred during the postoperative period for either group. CONCLUSION: Control of ossicular prosthesis positioning via the PT does not improve hearing results after ossicular chain reconstruction in cholesteatoma surgery. However, this approach can be used during a second-stage procedure that avoids incisions within the external ear canal. PMID- 26375973 TI - The Bony Obliteration Tympanoplasty in Pediatric Cholesteatoma: Long-term Safety and Hygienic Results. AB - OBJECTIVE: To present the safety and hygienic results of a 5-year longitudinal study in a pediatric population undergoing surgery for extensive cholesteatoma using a canal wall up approach with bony obliteration of the mastoid and epitympanic space. STUDY DESIGN: Retrospective consecutive study. PATIENTS: Thirty-three children (<=18 yr) undergoing surgery for cholesteatoma (34 ears) between 1997 and 2009. INTERVENTIONS: Therapeutic. SETTING: Tertiary referral center. MAIN OUTCOME MEASURES: 1) Residual and recurrent cholesteatoma rates at 5 year postsurgery, 2) postoperative waterproofing and hygienic status of the ear, and 3) required operation rate to achieve the safety and hygienic goals. RESULTS: At 5 years no patients were lost in follow-up. This consecutive series design is rare in chronical otitis media treatment reporting. The standard residual rate at 5 years was 5.8%, representing two residual cholesteatomas in the middle ear. The standard recurrence rate at 5 years was 2.9%, representing one recurrent cholesteatoma. At 5-year follow-up all ears were free of otorrhea and waterproof and all external ear canals were patent and self-cleaning. The operation rate to reach this safety and hygienic status was 1.5 operations per ear at 5-year follow up. CONCLUSION: The use of a canal wall up approach with obliteration of the mastoid cavity and epitympanic space to surgically treat cholesteatoma in children results in low residual and recurrence rates and a high rate of trouble free ears in the long term. PMID- 26375975 TI - Application and Interpretation of Resonance Frequency Analysis in Auditory Osseointegrated Implants: A Review of Literature and Establishment of Practical Recommendations. AB - OBJECTIVE: To establish standardization of implant stability measurements in auditory osseointegrated implants by means of resonance frequency analysis (RFA) through reviewing the currently published literature. METHODS: Studies reporting on RFA in auditory osseointegrated implants were identified, and the outcomes and the way these were reported were evaluated. RESULTS: Thirteen clinical studies reporting RFA outcomes of auditory osseointegrated implants were identified and analyzed, which demonstrated variations in methodology and reporting of data. The different reporting standards made a meta-analysis impossible. Heterogeneity and limitations were found in reporting of the types of implants, abutments, and SmartPegs used; study population sizes; follow-up duration; and, reporting of the implant stability quotient (ISQ). CONCLUSION: RFA is an interesting outcome of clinical studies on auditory osseointegrated implant research and might have potential as a clinically relevant tool for assessing implant stability. Because of the heterogeneous data that have been reported to date, the following guidelines for standardization of application and reporting were established. The implant and abutment type and length, and the type of SmartPeg should always be stated. Absolute stand-alone ISQ values should not be interpreted individually. ISQ values are at this moment most meaningful as a trend in the individual patient or in a population over time. No conclusions should be based on individual ISQ values. Standardized time points for RFA in research should be determined prospectively, with surgery as a baseline. After abutment replacement, individual ISQ trends from baseline cannot be interpreted anymore if the abutments differ in length. PMID- 26375974 TI - The Role of Obliteration in the Achievement of a Dry Mastoid Bowl. AB - OBJECTIVE: To evaluate the impact of mastoid obliteration on the achievement of a dry mastoid bowl and frequency of maintenance care. STUDY DESIGN: Retrospective chart review. SETTING: Academic medical center. PATIENTS: There were 63 canal wall-down mastoidectomies for chronic otitis media with or without cholesteatoma between 2007 and 2014 with follow-up of at least 6 months. Eighteen mastoids were nonobliterated and 45 were obliterated. Thirteen underwent secondary obliteration of existing mastoid bowls with chronic drainage, whereas 32 underwent primary obliteration at the original canal-wall-down procedure. INTERVENTION: Mastoid obliteration. MAIN OUTCOME MEASURES: Achievement of a dry healed mastoid cavity and frequency of outpatient visits. RESULTS: In more than 80% of the cases, a dry ear was achieved, with no significant difference between the obliterated and nonobliterated cases (p = 0.786). Eleven of the 13 secondary cases experienced cessation of otorrhea, achieving dry ears at rates similar to that of the primary and nonobliterated cases. The secondary obliteration population was also significantly younger than the primary group (22.1 versus 43.5 years, p = 0.002). Multivariable-mixed effects analysis demonstrated a reduction in 0.1 visits per 6 month period following surgery overtime (p < 0.001). CONCLUSIONS: Mastoid obliteration may be valuable in the management of the well-developed and chronically wet mastoid cavity, particularly when the drainage emanates from mucosal disease or cell tracts in a deep sinodural angle. Younger patients may require secondary obliteration because of continued craniofacial maturation several years following canal-wall-down surgery. PMID- 26375976 TI - A Comparative Study of Audiologic Outcomes for Two Transcutaneous Bone-Anchored Hearing Devices. AB - OBJECTIVE: In 1977, Tjellstrom et al. used the concept of osseointegration and implanted patients with a titanium screw as part of the first bone-anchored hearing solution. Despite good hearing outcomes with the percutaneous device, there has been a drive for the development of transcutaneous bone conduction systems because of soft tissue complications, aesthetics, and loss or failure of the abutment. This study compares audiologic and quality of life questionnaire outcomes (author-designed questionnaire) for two transcutaneous bone conduction implants. STUDY DESIGN: Cross-sectional cohort study. SETTING: Tertiary referral hospital and national audiology service. PATIENTS: Twelve patients, 10 children and two adults. Six recipients of each device. MAIN OUTCOME MEASURES: Pure-tone audiometry, aided thresholds, speech discrimination scores, and quality of life questionnaire results. RESULTS: The unaided four-frequency average air conduction for affected ears was 60.8 dB HL for the Attract group and 57.8 dBHL for the Sophono group; these improved to mean aided thresholds of 30.6 dB HL and 29.8 dB HL, respectively. Therewas no statistical difference between the speech discrimination scores for the two devices in quiet at 55 dB SPL (p = 0.33) orin noise (p = 0.87). CONCLUSION: Both systems provide audiologic benefit compared with the unaided situation. Comparing small numbers of patients, there was no significant difference in aided thresholds or speech discrimination scores between these two transcutaneous bone-anchored implants. All Attract and Sophono users reported improvement in quality of life and would recommend their device to others in a similar situation. PMID- 26375977 TI - Preliminary Report on the Investigation of the Association Between BPPV and Osteoporosis Using Biomarkers. AB - OBJECTIVE: To test the hypothesis that levels of a BPPV biomarker, otolin-1, correlate with those of osteoporosis markers, aminoterminal propeptide of protocollagen type I (P1NP), and aminoterminal telopeptides of collagen (NTX), thus further supporting a link between the two diseases. STUDY DESIGN: Prospective pilot clinical trial (Level of Evidence: 2b). PATIENTS: Postmenopausal women with BPPV. INTERVENTIONS: Diagnostic. MAIN OUTCOME MEASURES: Serum levels of otolin-1, P1NP, NTX, vitamin D, and calcium were examined in relation to each other, age, and DEXA scan T-scores. RESULTS: There was a strong, negative correlation between T-scores and otolin-1 levels. Although P1NP and NTX levels were strongly correlated, neither had statistical correlations with otolin 1. CONCLUSIONS: Despite a strong correlation between DEXA scan results and otolin 1 levels, there were no significant correlations between otolin-1 and P1NP or NTX. This suggests that the association between osteoporosis and BPPV is complex, but not likely to be causal. Although more work is needed to elucidate these relationships, this preliminary finding has important practical implications for BPPV in that proactive management of osteoporosis, per se, would not be expected to have benefits in management of BPPV. PMID- 26375978 TI - Peripheral Vestibular System Disease in Vestibular Schwannomas: A Human Temporal Bone Study. AB - INTRODUCTION: Dizziness is a common symptom in patients with vestibulo-cochlear schwannoma (VS), and several recent studies have identified this symptom as the single most important concerning the quality of life. Clinical and histological observations regarding hearing loss have suggested that this may be caused by both cochlear and retrocochlear mechanisms. Multiple mechanisms may also be at play in the case of dizziness, which may broaden perspectives of therapeutic approach. This study presents a systematic and detailed assessment of vestibular histopathology in temporal bones from patients with VS. METHODS: Retrospective analysis of vestibular system histopathology in temporal bones from 17 patients with unilateral VS. The material was obtained from The Copenhagen Temporal Bone Collection. RESULTS: Vestibular schwannomas were associated with atrophy of the vestibular ganglion, loss of fiber density of the peripheral vestibular nerve branches, and atrophy of the neuroepithelium of the vestibular end organs. In cases with small tumors, peripheral disease occurred only in the tissue structures innervated by the specific nerve from which the tumor originated. CONCLUSION: Vestibular schwannomas are associated with distinctive disease of the peripheral vestibular tissue structures, suggesting anterograde degeneration and that dizziness in these patients may be caused by deficient peripheral vestibular nerve fibers, neurons, and end organs. In smaller tumors, a highly localized disease occurs, which opens perspectives of differentiated clinical assessment and subsequent, targeted therapy. PMID- 26375979 TI - A Novel Temporal Bone Simulation Model Using 3D Printing Techniques. AB - HYPOTHESIS: An inexpensive temporal bone model for use in a temporal bone dissection laboratory setting can be made using a commercially available, consumer-grade 3D printer. BACKGROUND: Several models for a simulated temporal bone have been described but use commercial-grade printers and materials to produce these models. The goal of this project was to produce a plastic simulated temporal bone on an inexpensive 3D printer that recreates the visual and haptic experience associated with drilling a human temporal bone. METHODS: Images from a high-resolution CT of a normal temporal bone were converted into stereolithography files via commercially available software, with image conversion and print settings adjusted to achieve optimal print quality. The temporal bone model was printed using acrylonitrile butadiene styrene (ABS) plastic filament on a MakerBot 2x 3D printer. Simulated temporal bones were drilled by seven expert temporal bone surgeons, assessing the fidelity of the model as compared with a human cadaveric temporal bone. Using a four-point scale, the simulated bones were assessed for haptic experience and recreation of the temporal bone anatomy. RESULTS: The created model was felt to be an accurate representation of a human temporal bone. All raters felt strongly this would be a good training model for junior residents or to simulate difficult surgical anatomy. Material cost for each model was $1.92. CONCLUSIONS: A realistic, inexpensive, and easily reproducible temporal bone model can be created on a consumer-grade desktop 3D printer. PMID- 26375980 TI - Dexamethasone Protects Against Apoptotic Cell Death of Cisplatin-exposed Auditory Hair Cells In Vitro. AB - HYPOTHESIS: Dexamethasone (DXM) protects against cisplatin-induced auditory hair cell (HC) loss in rat organ of Corti (OC) explants in vitro by reducing levels of oxidative stress and NADPH-Oxidase-3 (NOX-3). BACKGROUND: Intratympanic DXM has demonstrated protective effects against cisplatin-induced hearing loss in a few animal studies and one clinical trial. However, levels of protection with intratympanic DXM vary significantly between studies, which may not be a result of the intrinsic properties of DXM but rather reflect the diffusion of DXM into the cochlea. The molecular mechanisms and degree of DXM protection against cisplatin ototoxicity are currently unknown. METHODS: OC explants from 3-day-old rats were cultured with no treatment or various concentrations of cisplatin (2, 5, or 10 MUM) and DXM (75, 150, or 300 MUg/mL) in vitro. HC viability and TUNEL assay were performed after 72 hours in vitro and levels of oxidative stress and NOX-3 were evaluated with confocal microscopy after 48 hours in vitro. Analysis of variance with Tukey's post hoc testing was performed. RESULTS: Cisplatin initiated dose-dependent losses of outer HCs (OHCs) in the basal turns of exposed explants (p < 0.001). DXM protected against cisplatin (2 MUM)-induced OHC loss in a dose-dependent manner with complete protection at 300 MUg/mL of DXM (p < 0.001). DXM (150 MUg/mL) significantly reduced levels of oxidative stress, NOX-3, and apoptosis in the basal turn of explants exposed to cisplatin (2 MUM). CONCLUSIONS: DXM protects against cisplatin-induced loss of OHCs in the basal turn of rat OC explants as demonstrated by reductions in oxidative stress and NOX 3 production and decreased levels of apoptotic cell death. PMID- 26375981 TI - Trans-Oval-Window Implants, A New Approach for Drug Delivery to the Inner Ear: Extended Dexamethasone Release From Silicone-based Implants. AB - HYPOTHESIS: The purpose of this study was to develop a new strategy to deliver drugs to the inner ear from dexamethasone (DXM)-loaded silicone implants and to evaluate the distribution of the drug in the cochlea with confocal microscopy. BACKGROUND: Systemic drug administration for the treatment of inner ear disorders is tricky because of the blood-cochlear barrier, a difficult anatomical access, the small size of the cochlea, and can cause significant adverse effects. An effective way to overcome these obstacles is to administer drugs locally. METHODS: In vitro, the drug release from DXM-loaded silicone-based thin films and tiny implants into artificial perilymph was thoroughly analyzed by high performance liquid chromatography. In vivo, a silicone implant loaded with 10% DXM and 5% polyethylene glycol 400 was implanted next to the stapes's footplate of gerbils. Delivery of DXM into the inner ear was proved by confocal microscopy imaging of the whole cochlea and the organ of Corti. RESULTS: The study showed a continuous and prolonged release during 90 days in vitro. This was confirmed by confocal microscopy that allowed detection of DXM by fluorescence labeling in the cell body of the hair cells for at least 30 days. Interestingly, fluorescence was already observed after 20 minutes of implantation, reached a climax at day 7, and could still be detected 30 days after implantation. CONCLUSIONS: Thus, we developed a new device for local corticosteroids delivery into the oval window with an extended drug release of DXM to the inner ear. PMID- 26375982 TI - Intratympanic Steroid Injection for Bell's Palsy: Some Issues Highlighted. PMID- 26375983 TI - Reply to the Letter to the Editor: Intratympanic Steroid Injection for Bell's Palsy: Some Issues Highlighted. PMID- 26375984 TI - Prognostic Relevance of Cytokine Receptor Expression in Acute Myeloid Leukemia: Interleukin-2 Receptor alpha-Chain (CD25) Expression Predicts a Poor Prognosis. AB - A variety of cytokine/cytokine receptor systems affect the biological behavior of acute leukemia cells. However, little is known about the clinical relevance of cytokine receptor expression in acute myeloid leukemia (AML). We quantitatively examined the expression of interleukin-2 receptor alpha-chain (IL-2Ralpha, also known as CD25), IL-2Rbeta, IL-3Ralpha, IL-4Ralpha, IL-5Ralpha, IL-6Ralpha, IL 7Ralpha, the common beta-chain (betac), gammac, granulocyte-macrophage colony stimulating factor (GM-CSF)Ralpha, G-CSFR, c-fms, c-mpl, c-kit, FLT3, and GP130 in leukemia cells from 767 adult patients with AML by flow cytometry and determined their prevalence and clinical significance. All cytokine receptors examined were expressed at varying levels, whereas the levels of IL-3Ralpha, GM CSFRalpha, IL-2Ralpha, gammac, c-kit, and G-CSFR exhibited a wide spectrum of >=10,000 sites/cell. In terms of their French-American-British classification types, GM-CSFRalpha and c-fms were preferentially expressed in M4/M5 patients, G CSF in M3 patients, and IL-2Ralpha in non-M3 patients. Elevated levels of IL 3Ralpha, GM-CSFRalpha, and IL-2Ralpha correlated with leukocytosis. In patients <=60 years old, higher levels of these 3 receptors correlated with poor responses to conventional chemotherapy, but only IL-2Ralpha was associated with a shorter overall survival. By incorporating IL-2Ralpha status into cytogenetic risk stratification, we could sort out a significantly adverse-risk cohort from the cytogenetically intermediate-risk group. Analyses with various phenotypical risk markers revealed the expression of IL-2Ralpha as an independent prognostic indicator in patients with intermediate-risk cytogenetics. These findings were not observed in patients >60 years old. Our results indicate that several cytokine receptors were associated with certain cellular and clinical features, but IL-2Ralpha alone had prognostic value that provides an additional marker to improve current risk evaluation in AML patients <=60 years old. PMID- 26375985 TI - A phosphomimetic mutant of RelA/p65 at Ser536 induces apoptosis and senescence: An implication for tumor-suppressive role of Ser536 phosphorylation. AB - Hundreds of NF-kappaB inhibitors have been developed for cancer therapy, but their clinical efficacy is unsatisfactory. Here we show that the phosphorylation activation at Ser536 of RelA/p65 protein, a main subunit in the NF-kappaB family, may play a tumor-suppressive role. In normal colon mucosa, RelA/p65 phosphorylation at Ser536 was increasingly increased with the maturation and apoptotic shedding of epithelial cells, but the phosphorylation at Ser536 was decreased in colon cancer. In colon (HCT116 p53 wt and p53 -/-), breast (MCF7), and prostate (LNCaP and DU145) cancer cells, a phosphomimetic mutation of RelA/p65 at Ser536 (named p65/S536D) triggered dramatic apoptosis through affecting expression of a wide range of cell death/survival genes, such as Bim, Puma, Noxa, Bcl-2 and survivin. In HCT116 cells, p65/S536D mutant upregulated Fas, insulted mitochondrial membrane potential, and triggered cleavage and activation of caspase-3, 7, 8 and 9. A FasL neutralizing antibody (NOK1) prevented cell death induced by the p65/S536D. A pan inhibitor of caspases, Z-VAD FMK (20 MUM), blocked caspase-mediated mitochondrial membrane depolarization. This p65/S536D also triggered senescence in HCT116 cells through a p16-dependent pathway, but not in MFC7 due to lack of p16. Intratumoral delivery of the p65/S536D effectively suppressed tumor growth in nude mice. Together our data suggest that the phosphorylation of RelA/p65 at Ser536 may confer it a tumor suppressive role by inducing apoptosis and senescence, highlighting the importance of discriminating the function and active status of individual active sites in RelA/p65 when NF-kappaB inhibitors are considered for targeted therapy of cancer. PMID- 26375986 TI - Quillajasides A and B: New Phenylpropanoid Sucrose Esters from the Inner Bark of Quillaja saponaria Molina. AB - The phenolic composition of freshly prepared aqueous extracts of the inner bark of Quillaja saponaria Molina was compared to that of commercially available Quillaja extracts, which are currently used as emulsifiers in foods and cosmetics. Major phenolics in both extracts were (+)-piscidic acid and several p coumaroyl sucrose esters. Among the latter, two new compounds were isolated and characterized: alpha-l-rhap-(1->4)-alpha-l-rhap-(1->3)-(4-O-(E)-p-coumaroyl) alpha-d-glup-(1->2)-(3-O-(E)-p-coumaroyl)-beta-d-fruf (quillajaside A) and beta-d apif-(1->4)-alpha-l-rhap-(1->4)-alpha-l-rhap-(1->3)-(4-O-(E)-p-coumaroyl)-alpha-d glup-(1->2)-(3-O-(E)-p-coumaroyl)-beta-d-fruf (quillajaside B). In addition, a putative biosynthetic pathway of at least 20 structurally related p-coumaroyl sucrose esters was tentatively identified. Besides their antioxidant activity and their potential function as substrate for enzymatic browning reactions, the new compounds are highly characteristic for both the inner bark of Q. saponaria and commercial extracts derived therefrom. Consequently, they might serve as authenticity markers for the detection of Quillaja extracts in food and cosmetic formulations. PMID- 26375987 TI - Is Metabolic and Bariatric Surgery a Population Solution for Obesity and Type 2 Diabetes? PMID- 26375989 TI - Body Posture After Mastectomy: Comparison Between Immediate Breast Reconstruction Versus Mastectomy Alone. AB - BACKGROUND: Immediate breast reconstruction has been increasingly incorporated as part of breast cancer treatment, especially for the psychological benefits. Currently, there are many options for breast reconstruction surgery, but the impact of the different techniques on body posture has not been widely studied. One study demonstrated that immediate breast reconstruction with a Beker-25 prosthesis could help to preserve body posture after mastectomy; however, there is no evidence regarding the effect of surgery on the body posture of women after breast reconstruction when using autologous tissue. PURPOSE: The purpose of this paper is to compare the body postures of women who underwent immediate breast reconstruction using an abdominal flap with those of women who underwent mastectomy alone. DESIGN: This is a cross-sectional study. SUBJECTS: Seventy-six women diagnosed with breast cancer underwent mastectomy, between 1 and 5 years after the diagnosis, are the participants of the study. Two groups were defined: women who underwent mastectomy and immediate breast reconstruction (n = 38) and women who underwent mastectomy alone (n = 38). PROCEDURE: To assess body posture, specific anatomical points for obtaining photographs were located and marked in anterior, posterior and right-side and left-side views. The photographs were analysed using Postural Analysis Software/Software de Analise Postural (PAS/SAPO). RESULTS: In the left lateral view, there was a significant difference in the vertical alignment of the trunk (4.2 vs 3.1; p = 0.05). There were no significant differences between the two groups for the variables in the anterior, posterior or right-side views. CONCLUSION: Women who underwent mastectomy alone, compared with women who underwent immediate breast reconstruction with abdominal flaps, showed differences in the vertical alignment of the trunk, with greater asymmetry between the acromion and greater trochanter, which can mean trunk rotation. No significant differences were found between the two groups in the alignment of the head, shoulders, scapula, or pelvis. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26375988 TI - Methylseleninic acid promotes antitumour effects via nuclear FOXO3a translocation through Akt inhibition. AB - Selenium supplement has been shown in clinical trials to reduce the risk of different cancers including lung carcinoma. Previous studies reported that the antiproliferative and pro-apoptotic activities of methylseleninic acid (MSA) in cancer cells could be mediated by inhibition of the PI3K pathway. A better understanding of the downstream cellular targets of MSA will provide information on its mechanism of action and will help to optimize its use in combination therapies with PI3K inhibitors. For this study, the effects of MSA on viability, cell cycle, metabolism, apoptosis, protein and mRNA expression, and reactive oxygen species production were analysed in A549 cells. FOXO3a subcellular localization was examined in A549 cells and in stably transfected human osteosarcoma U2foxRELOC cells. Our results demonstrate that MSA induces FOXO3a nuclear translocation in A549 cells and in U2OS cells that stably express GFP FOXO3a. Interestingly, sodium selenite, another selenium compound, did not induce any significant effects on FOXO3a translocation despite inducing apoptosis. Single strand break of DNA, disruption of tumour cell metabolic adaptations, decrease in ROS production, and cell cycle arrest in G1 accompanied by induction of apoptosis are late events occurring after 24h of MSA treatment in A549 cells. Our findings suggest that FOXO3a is a relevant mediator of the antiproliferative effects of MSA. This new evidence on the mechanistic action of MSA can open new avenues in exploiting its antitumour properties and in the optimal design of novel combination therapies. We present MSA as a promising chemotherapeutic agent with synergistic antiproliferative effects with cisplatin. PMID- 26375990 TI - Frequencies, Laboratory Features, and Granulocyte Activation in Chinese Patients with CALR-Mutated Myeloproliferative Neoplasms. AB - Somatic mutations in the CALR gene have been recently identified as acquired alterations in myeloproliferative neoplasms (MPNs). In this study, we evaluated mutation frequencies, laboratory features, and granulocyte activation in Chinese patients with MPNs. A combination of qualitative allele-specific polymerase chain reaction and Sanger sequencing was used to detect three driver mutations (i.e., CALR, JAK2V617F, and MPL). CALR mutations were identified in 8.4% of cases with essential thrombocythemia (ET) and 5.3% of cases with primary myelofibrosis (PMF). Moreover, 25% of polycythemia vera, 29.5% of ET, and 48.1% of PMF were negative for all three mutations (JAK2V617F, MPL, and CALR). Compared with those patients with JAK2V617F mutation, CALR-mutated ET patients displayed unique hematological phenotypes, including higher platelet counts, and lower leukocyte counts and hemoglobin levels. Significant differences were not found between Chinese PMF patients with mutants CALR and JAK2V617F in terms of laboratory features. Interestingly, patients with CALR mutations showed markedly decreased levels of leukocyte alkaline phosphatase (LAP) expression, whereas those with JAK2V617F mutation presented with elevated levels. Overall, a lower mutant rate of CALR gene and a higher triple-negative rate were identified in the cohort of Chinese patients with MPNs. This result indicates that an undiscovered mutant gene may have a significant role in these patients. Moreover, these pathological features further imply that the disease biology varies considerably between mutants CALR and JAK2V617F. PMID- 26375991 TI - Hunting, Exotic Carnivores, and Habitat Loss: Anthropogenic Effects on a Native Carnivore Community, Madagascar. AB - The wide-ranging, cumulative, negative effects of anthropogenic disturbance, including habitat degradation, exotic species, and hunting, on native wildlife has been well documented across a range of habitats worldwide with carnivores potentially being the most vulnerable due to their more extinction prone characteristics. Investigating the effects of anthropogenic pressures on sympatric carnivores is needed to improve our ability to develop targeted, effective management plans for carnivore conservation worldwide. Utilizing photographic, line-transect, and habitat sampling, as well as landscape analyses and village-based bushmeat hunting surveys, we provide the first investigation of how multiple forms of habitat degradation (fragmentation, exotic carnivores, human encroachment, and hunting) affect carnivore occupancy across Madagascar's largest protected area: the Masoala-Makira landscape. We found that as degradation increased, native carnivore occupancy and encounter rates decreased while exotic carnivore occupancy and encounter rates increased. Feral cats (Felis species) and domestic dogs (Canis familiaris) had higher occupancy than half of the native carnivore species across Madagascar's largest protected landscape. Bird and small mammal encounter rates were negatively associated with exotic carnivore occupancy, but positively associated with the occupancy of four native carnivore species. Spotted fanaloka (Fossa fossana) occupancy was constrained by the presence of exotic feral cats and exotic small Indian civet (Viverricula indica). Hunting was intense across the four study sites where hunting was studied, with the highest rates for the small Indian civet (mean=90 individuals consumed/year), the ring-tailed vontsira (Galidia elegans) (mean=58 consumed/year), and the fosa (Cryptoprocta ferox) (mean=31 consumed/year). Our modeling results suggest hunters target intact forest where carnivore occupancy, abundance, and species richness, are highest. These various anthropogenic pressures and their effects on carnivore populations, especially increases in exotic carnivores and hunting, have wide-ranging, global implications and demand effective management plans to target the influx of exotic carnivores and unsustainable hunting that is affecting carnivore populations across Madagascar and worldwide. PMID- 26375992 TI - Adverse Effects of Common Drugs: Foreword. PMID- 26375993 TI - Adverse Effects of Common Drugs: General Concepts. AB - Adverse drug reactions (ADRs) contribute to substantial morbidity and mortality and add to rising health care costs. Many ADRs are preventable with appropriate prescribing and monitoring because they often occur as an extension of a drug's mechanism of action or known drug interactions. Patients at higher risk of ADRs include those at the extremes of age, those with multiple comorbidities, those taking multiple drugs, and patients admitted to intensive care units or experiencing transitions of care. Because the risk of ADRs becomes greater as the number of drugs and dietary supplements taken increases, it is imperative that prescribers be vigilant about the prescribing cascade and take steps to discontinue drugs that are likely to be more harmful than helpful. Pharmacists serve as important partners in clinical care environments by conducting comprehensive drug reviews, aiding in drug/dosage selection, and developing therapeutic monitoring plans. Although the potential exists for clinicians to use electronic health record systems to aid in clinical decision making through drug safety decision support tools, computer systems should never replace clinical judgment. Clinicians also are encouraged to report ADRs to the Food and Drug Administration Adverse Event Reporting System. PMID- 26375995 TI - Adverse Effects of Common Drugs: Adults. AB - Although drugs can be an essential and lifesaving component of the care of adult patients, their use frequently is accompanied by adverse effects and life threatening adverse drug reactions that can result in significant disability and mortality. The potential for drug-related severe morbidity and mortality is compounded during periods of hospitalization, when high-risk drugs such as anticoagulants or insulin are used, and when care in an intensive care unit is required. Patient factors in adults that can increase the risk of drug harms include immunosuppression, cognitive impairment, depression, alcoholism and other substance abuse disorders, chronic kidney disease, hepatic dysfunction, coagulopathies, limited English proficiency, institutional/nursing home care, and underinsurance or lack of insurance. Physician factors that can increase the risk of drug harms include inappropriate prescribing of drugs (including to pregnant and breastfeeding women), failure to appropriately discontinue/deprescribe drugs, insufficient drug reconciliation, failure to coordinate care among multiple prescribing clinicians, and failure to elicit and incorporate into health histories and clinical decision-making the widespread use of nonprescription drugs, herbal products, and dietary supplements. PMID- 26375994 TI - Adverse Effects of Common Drugs: Children and Adolescents. AB - Drug use and harms are increasingly common among newborns, infants, children, and adolescents during ambulatory practice, emergency department, and in-hospital treatment, including treatment in pediatric intensive care units. The pharmacokinetic and pharmacodynamic parameters of drugs often are different for children compared with adults and must be considered before prescribing. Drug exposure and the potential for harms also should be considered for fetuses and breastfeeding infants. As with adult patients, a thorough drug and allergy history (including nonprescription drugs and herbal and dietary supplements) should be obtained and reviewed at each medical visit. Children and adolescents are increasingly at risk of drug harm/overdose through accidental or intentional ingestion of nonprescription and prescription drugs (eg, cough and cold preparations, candy-appearing vitamins, stimulants, narcotics). Parents and caregivers should receive training in the proper use, storage, and administration of all drugs. Prescribing clinicians should be vigilant in withholding unnecessary drugs, such as antibiotics for viral infections. When prescribing, clinicians should be aware of common drugs frequently associated with adverse reactions, including stimulants, antipsychotics, analgesics, asthma therapies, acne therapies, and tumor necrosis factor inhibitors. Scientifically based prescribing practices should be used and consultation with evidence-based resources and pharmacists sought as needed. PMID- 26375996 TI - Adverse Effects of Common Drugs: Dietary Supplements. AB - Dietary supplement-induced adverse effects often resolve quickly after discontinuation of the offending product, especially in younger patients. The potential for unwanted outcomes can be amplified in elderly patients or those taking multiple prescription drugs, especially where interactions exist with drugs metabolized by cytochrome P450 enzymes. Attributing injury or illness to a specific supplement can be challenging, especially in light of multi-ingredient products, product variability, and variability in reporting, as well as the vast underreporting of adverse drug reactions. Clinicians prescribing a new drug or evaluating a patient with a new symptom complex should inquire about use of herbal and dietary supplements as part of a comprehensive evaluation. Clinicians should report suspected supplement-related adverse effects to the local or state health department, as well as the Food and Drug Administration's MedWatch program (available at https://www.safetyreporting.hhs.gov). Clinicians should consider discussing suspected adverse effects involving drugs, herbal products, or dietary supplements with their community- and hospital-based pharmacists, and explore patient management options with medical or clinical toxicology subspecialists. PMID- 26375997 TI - Theoretical Analysis of the Fragmentation of (CO)5: A Symmetry-Allowed Highly Exothermic Reaction that Follows a Stepwise Pathway. AB - B3LYP and CCSD(T) calculations, using an aug-cc-pVTZ basis set, have been carried out on the fragmentation of 1,2,3,4,5-cyclopentanepentone, (CO)(5), to five molecules of CO. Although this reaction is calculated to be highly exothermic and is allowed to be concerted by the Woodward-Hoffmann rules, our calculations find that the D(5h) energy maximum is a multidimensional hilltop on the potential energy surface. This D(5h) hilltop is 16-20 kcal/mol higher in energy than a C(2) transition structure for the endothermic cleavage of (CO)(5) to (CO)(4) + CO and 11-15 kcal/mol higher than a C(s) transition structure for the loss of two CO molecules. The reasons for the very high energy of the D(5h) hilltop are discussed, and the geometries of the two lower energy transition structures are rationalized on the basis of mixing of the e(2)' HOMO and the a(2)" LUMO of the hilltop. PMID- 26375998 TI - Clinical Research Abstracts of the British Equine Veterinary Association Congress 2015. AB - REASONS FOR PERFORMING STUDY: Hypoglycin A (HG) appears to cause atypical myopathy (AM), but to our knowledge, detection of HG in affected and unaffected horses and concurrently in plants that they were exposed to has not previously been reported. OBJECTIVES: To investigate HG in samples from horses exposed to Acer pseudoplatanus (European sycamore maple) and in such plant material, at the time of clinical cases of AM in the herd. STUDY DESIGN: Cross-sectional study. METHODS: Blood was collected from 2 horses with AM and 22 clinically healthy co grazing horses in 2 Swedish farms within one week of onset of signs (May 2014) and one month later, after horses were moved to other pastures. Ten healthy control horses from unaffected farms were sampled once. Samaras, seedlings, flowers and leaves from Acer pseudoplatanus and from Acer platanoides L (Norway maple) were collected from affected pastures. Hypoglycin A was analysed using chemical derivatisation with dansyl chloride (DNS) and ultra high performance liquid chromatography-tandem mass spectrometry. Hypoglycin A was detected as derivatised compound HG-DNS [M+H]+ with selected reaction monitoring. RESULTS: Hypoglycin A was detected in the horses affected with AM, and also in 20 out of 22 co-grazing horses. One month later, a surviving case horse and 9/20 co-grazing horses were still positive for HG. Controls from other farms were negative for HG. Hypoglycin A was detected in plant material from Acer pseudoplatanus, but not from Acer platanoides L. CONCLUSIONS: Horses grazing in pastures with HG containing Acer pseudoplatanus were positive for HG in blood, and some showed severe signs of myopathy. Ethical animal research: Ethical consent for blood sampling was granted (C113/11) and horse owners gave their informed consent to inclusion of horses in the study. SOURCE OF FUNDING: National Veterinary Institute, Sweden. Competing interests: None declared. PMID- 26375999 TI - Data mining The Cancer Genome Atlas in the era of precision cancer medicine. AB - The Cancer Genome Atlas (TCGA) has given researchers and clinicians unprecedented access to many different cancers through multiple platforms that include exome sequencing, comparative genomic hybridisation (CGH) arrays, DNA methylation arrays, RNA sequencing, reverse protein phase arrays (RPPA), and clinical features. Most data are available to the public in their raw and processed forms; however, analysis and interpretation of these data require specialised training and software. To address this problem, online tools such as cBioportal, canEvolve, GDAC firehose, PROGgeneV2, and UCSC Cancer browser have been developed by various groups to explore and perform analyses on the datasets that are easily understandable by basic researchers and clinicians. In this mini-review, we give an overview of the datasets available from TCGA and the public tools available for integrative analysis of survival with the genomic and transcriptomic datasets, and introduce a tool being developed by our group to analyse the datasets within TCGA. PMID- 26376000 TI - Thickness-Gradient Films for High Gauge Factor Stretchable Strain Sensors. AB - High-gauge-factor stretchable strain sensors are developed by utilizing a new strategy of thickness-gradient films with high durability, and high uniaxial/isotropic stretchability based on the self-pinning effect of SWCNTs. The monitoring of detailed damping vibration modes driven by weak sound based on such sensors is demonstrated, making a solid step toward real applications. PMID- 26376001 TI - Friction and morphology of pleural mesothelia. AB - To verify the hypothesis that by enmeshing lubricants, microvilli reduce the coefficient of kinetic friction (MU) of pleural mesothelium, MU was measured during reciprocating sliding of rabbit's visceral against parietal pleura before and after addition of hyaluronan, and related to the morphological features of the microvillar network. Because no relation was found between MU or MU changes after hyaluronan and microvillar characteristics, the latter are not determinants of the frictional forces which oppose sliding of normal mesothelial surfaces under physiological conditions, nor of the effects of hyaluronan. Addition of hyaluronan increased MU slightly but significantly in normal specimens, probably by altering the physiological mix of lubricants, but decreased MU of damaged mesothelia, suggesting protective, anti-abrasion properties. Indeed, while sliding of an injured against a normal pleura heavily damaged the latter and increased MU when Ringer was interposed between the surfaces, both effects were limited or prevented when hyaluronan was interposed between the injured and normal pleura before onset of sliding. PMID- 26376002 TI - Airway compliance and dynamics explain the apparent discrepancy in length adaptation between intact airways and smooth muscle strips. AB - Length adaptation is a phenomenon observed in airway smooth muscle (ASM) wherein over time there is a shift in the length-tension curve. There is potential for length adaptation to play an important role in airway constriction and airway hyper-responsiveness in asthma. Recent results by Ansell et al., 2015 (JAP 2014 10.1152/japplphysiol.00724.2014) have cast doubt on this role by testing for length adaptation using an intact airway preparation, rather than strips of ASM. Using this technique they found no evidence for length adaptation in intact airways. Here we attempt to resolve this apparent discrepancy by constructing a minimal mathematical model of the intact airway, including ASM which follows the classic length-tension curve and undergoes length adaptation. This allows us to show that (1) no evidence of length adaptation should be expected in large, cartilaginous, intact airways; (2) even in highly compliant peripheral airways, or at more compliant regions of the pressure-volume curve of large airways, the effect of length adaptation would be modest and at best marginally detectable in intact airways; (3) the key parameters which control the appearance of length adaptation in intact airways are airway compliance and the relaxation timescale. The results of this mathematical simulation suggest that length adaptation observed at the level of the isolated ASM may not clearly manifest in the normal intact airway. PMID- 26376003 TI - Impact of Types of Moisturizer and Humidity on the Residual Weight and Viscosity of Liquid and Gel Oral Moisturizers. AB - PURPOSE: Oral moisturizers need to be selected based on their material properties. The purpose of this study was to investigate the effects of moisturizer type and humidity on the residual weight and viscosity of oral moisturizers. MATERIALS AND METHODS: The weight and viscosity of 17 oral moisturizers (7 liquid and 10 gel) at baseline and after 8 hours were measured using an incubator maintained at 37 degrees C at either 85% or 40% relative humidity (RH). The rate of change in weight (RCW) and the rate of change in viscosity (RCV) were calculated. Data were analyzed with two-way analysis of variance (ANOVA) and Scheffe's test to evaluate the effect of the type of moisturizer (liquid or gel) and humidity (85% or 40% RH) on RCW and RCV. Pearson's correlation coefficient was used to evaluate the relationship between RCW and RCV. RESULTS: Two-way ANOVA results indicated that the type of moisturizer and RH had a significant effect on RCW and RCV (p < 0.05); however, the interaction between them was not significant. The results of multiple comparisons showed that gel moisturizers had a significantly lower RCW and higher RCV than liquid moisturizers (p < 0.05). The RCW and RCV at 40% RH were significantly higher than those at 85% RH (p < 0.05). There was no correlation between RCW and RCV in the liquid moisturizer group, but a significant negative correlation was found in the gel moisturizer group (pp = 0.01). CONCLUSION: Because viscosity of gel moisturizers increases as weight decreases, selecting gel moisturizers with a minimal change in weight and viscosity would be preferable in the case of a long-time application and severe dry mouth. PMID- 26376004 TI - Surviving metabolic arrest: photosynthesis during desiccation and rehydration in resurrection plants. AB - Photosynthesis is the key process that is affected by dehydration in plants. Desiccation-tolerant resurrection plants can survive conditions of very low relative water content. During desiccation, photosynthesis is not operational, but is recovered within a short period after rehydration. While homoiochlorophyllous resurrection plants retain their photosynthetic apparatus during desiccation, poikilochlorophyllous resurrection species dismantle chloroplasts and degrade chlorophyll but resynthesize them again during rehydration. Dismantling the chloroplasts avoids the photooxidative stress in poikilochlorophyllous resurrection plants, whereas it is minimized in homoiochlorophyllous plants through the synthesis of antioxidant enzymes and protective proteins or metabolites. Although the cellular protection mechanisms in both of these species vary, these mechanisms protect cells from desiccation induced damage and restore photosynthesis upon rehydration. Several of the proteins synthesized during dehydration are localized in chloroplasts and are believed to play major roles in the protection of photosynthetic structures and in recovery in resurrection species. This review focuses on the strategies of resurrection plants in terms of how they protect their photosynthetic apparatus from oxidative stress during desiccation without membrane damage and with full recovery during rehydration. We review the role of the dehydration-induced protection mechanisms in chloroplasts and how photosynthesis is restored during rehydration. PMID- 26376005 TI - Letter from Nepal, August 12, 2015--Cholera in post-earthquake Kathmandu. PMID- 26376006 TI - Silanized aryl layers through thiol-yne photo-click reaction. AB - Nanometer-scale multilayered coatings were prepared by sequential surface reactions on gold plates. First 4-ethynylphenyl organic layer was electrografted from the parent diazonium tetrafluoroborate salt providing reactive alkynylated gold plate (Au-Y). The latter served for clicking mercaptosilane via a thiol-yne photo-triggered reaction to obtain alkoxysilane-functionalized surface. The trialkoxysilane top groups in turn served as anchor sites for the final sol-gel coating resulting from the surface reaction between aminopropylsilane and tetraethoxysilane (TEOS). It is demonstrated that two coupling agents, namely, aryl diazonium salt and silane, can be coupled using photo-triggered thiol-yne click reaction, resulting in robust multilayered coatings. In addition, the process is versatile in that it offers the possibility to design patterned surfaces. The top sol-gel layer can in turn be reacted with aminosilane, therefore providing a reactive and functional surface that can be used for different applications given the reactivity of amine groups. This approach opens new avenues for photo-triggered click reactions of aryl layers from diazonium salts. It shows that the new class of surface modifiers and coupling agents has much to offer and continues to be renewed for achieving tightly bound, reactive top coatings. PMID- 26376007 TI - Introducing Computed Tomography Standards for Age Estimation of Modern Australian Subadults Using Postnatal Ossification Timings of Select Cranial and Cervical Sites(.). AB - Contemporary, population-specific ossification timings of the cranium are lacking in current literature due to challenges in obtaining large repositories of documented subadult material, forcing Australian practitioners to rely on North American, arguably antiquated reference standards for age estimation. This study assessed the temporal pattern of ossification of the cranium and provides recalibrated probabilistic information for age estimation of modern Australian children. Fusion status of the occipital and frontal bones, atlas, and axis was scored using a modified two- to four-tier system from cranial/cervical DICOM datasets of 585 children aged birth to 10 years. Transition analysis was applied to elucidate maximum-likelihood estimates between consecutive fusion stages, in conjunction with Bayesian statistics to calculate credible intervals for age estimation. Results demonstrate significant sex differences in skeletal maturation (p < 0.05) and earlier timings in comparison with major literary sources, underscoring the requisite of updated standards for age estimation of modern individuals. PMID- 26376008 TI - Rapid Cell Patterning Induced by Differential Topography on Silica Nanofractal Substrates. AB - Predesigned silica nanofractal substrates are utilized for rapid cell patterning, based on differential cell adhesion originating from surface topographic interactions. Cell patterns with various shapes are successfully formed, from simple geometrical shapes to a complex "CELL" symbol. This study assists understanding of cell-substrate interactions and facilitates biological applications. PMID- 26376009 TI - MicroRNA-1 effectively induces differentiation of myocardial cells from mouse bone marrow mesenchymal stem cells. AB - In this research, bone marrow mesenchymal stem cells (BMSCs) were isolated from mouse, and induced differentiation into myocardial cells in vitro after overexpression of miR-1a. The results showed that the BMSCs could induce differentiation into myocardial cells under the special condition medium, but when the miR-1a was over-expressed in BMSCs, the differentiation efficiency and induction time of myocardial cells from BMSCs could be promoted. This reason was demonstrated that Delta-like 1 (Dll-1) was a transcriptional repressor of myocardium gene expression during myocardium differentiation, miR-1a reduced Dll 1 levels, leading to the accumulation of myocardium gene mRNA and a dramatic increase in myocardium gene protein. PMID- 26376010 TI - Association between long-term erectile dysfunction and biochemical recurrence after permanent seed I(125) implant brachytherapy for prostate cancer. A longitudinal study of a single-institution. AB - We aimed to investigate the predictive factor of erectile dysfunction (ED) in prostate cancer (PCa) patients who underwent low-dose permanent I(125) seed implant brachytherapy and to investigate if ED could represent a patient's reported outcome measures (PROMs) of efficacy of BT and indirectly associated with biochemical recurrence free survival (BRFS). From 2000 to 2012, 176 consecutive patients with low-risk PCa underwent BT. ED was evaluated with the International Index of Erectile Function (IIEF-5). Cox regression analysis was performed to assess significant predictors of mild-to-severe ED and BRFS after BT, including covariates. The 10-year actuarial rate of ED was 66%. Subjects with severe ED had higher values of D90 (183.0 versus 177.0; p < 0.05) and V100% (40.1 versus 31.4; p < 0.05) compared with normal. At the multivariate logistic regression analysis, D90 (OR: 1.10; p < 0.05) was an independent predictor of ED. Multivariate Cox-regression analysis did not demonstrate significant association between erectile preservation and biochemical recurrence (BCR) after 10 years of follow up (HR: 2.15; p = 0.20), while D90 <= 180 Gy independently predicted BCR (HR: 4.65; [95%CI: 1.25-17.34]; p < 0.05). Erectile preservation should be addressed as valuable PROMs after permanent seed I(125) implant, but it is not associated with better BRFS. PMID- 26376011 TI - Fitting the two-compartment model in DCE-MRI by linear inversion. AB - PURPOSE: Model fitting of dynamic contrast-enhanced-magnetic resonance imaging MRI data with nonlinear least squares (NLLS) methods is slow and may be biased by the choice of initial values. The aim of this study was to develop and evaluate a linear least squares (LLS) method to fit the two-compartment exchange and filtration models. METHODS: A second-order linear differential equation for the measured concentrations was derived where model parameters act as coefficients. Simulations of normal and pathological data were performed to determine calculation time, accuracy and precision under different noise levels and temporal resolutions. Performance of the LLS was evaluated by comparison against the NLLS. RESULTS: The LLS method is about 200 times faster, which reduces the calculation times for a 256 * 256 MR slice from 9 min to 3 s. For ideal data with low noise and high temporal resolution the LLS and NLLS were equally accurate and precise. The LLS was more accurate and precise than the NLLS at low temporal resolution, but less accurate at high noise levels. CONCLUSION: The data show that the LLS leads to a significant reduction in calculation times, and more reliable results at low noise levels. At higher noise levels the LLS becomes exceedingly inaccurate compared to the NLLS, but this may be improved using a suitable weighting strategy. Magn Reson Med 76:998-1006, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26376012 TI - Letter from the Editor. PMID- 26376013 TI - Human Vaccines & Immunotherapeutics: News. PMID- 26376014 TI - Comparison of HPV prevalence between HPV-vaccinated and non-vaccinated young adult women (20-26 years). AB - There is some concern about the effectiveness of the HPV vaccine among young adult women due to the risk of prior HPV infection. This study used National Health and Nutrition Examination Survey (NHANES) 2007-2012 data to evaluate the effectiveness of HPV vaccination among women 20-26 years of age who were vaccinated after 12 years of age. This cross-sectional study examined 878 young adult women (20-26 years) with complete information on HPV prevalence and HPV vaccination status from NHANES 2007-2012. Vaginal swab specimens were analyzed for HPV DNA by L1 consensus polymerase chain reaction followed by type-specific hybridization. Multivariate logistic regression models controlling for sociodemographic characteristics and sexual behaviors were used to compare type specific HPV prevalence between vaccinated and unvaccinated women. A total of 21.4% of young adult women surveyed through NHANES between 2007 and 2012 received the HPV vaccine. Vaccinated women had a lower prevalence of vaccine types than unvaccinated women (7.4% vs 17.1%, prevalence ratio 0.43, 95% CI 0.21-0.88). The prevalence of high-risk nonvaccine types was higher among vaccinated women than unvaccinated women (52.1% vs 40.4%, prevalence ratio 1.29, 95% CI 1.06-1.57), but this difference was attenuated after adjusting for sexual behavior variables (adjusted prevalence ratio 1.19, 95% CI 0.99-1.43). HPV vaccination was effective against all 4 vaccine types in young women vaccinated after age 12. However, vaccinated women had a higher prevalence of high-risk nonvaccine types, suggesting that they may benefit from newer vaccines covering additional types. PMID- 26376015 TI - Factors influencing preclinical in vivo evaluation of mumps vaccine strain immunogenicity. AB - Immunogenicity testing in animals is a necessary preclinical assay for demonstration of vaccine efficacy the results of which are often the basis for the decision whether to proceed or withdraw the further development of the novel vaccine candidate. However, in vivo assays are rarely, if at all, optimized and validated. Here we clearly demonstrate the importance of in vivo assay (mumps virus immunogenicity testing in guinea pigs) optimization for gaining reliable results and the suitability of Fractional factorial design of experiments (DoE) for such a purpose. By the use of DoE with resolution IV (2IV((4-1))) we clearly revealed that the parameters significantly increasing assay sensitivity were interval between animal immunizations followed by the body weight of experimental animals. The quantity (0 versus 2%) of the stabilizer (fetal bovine serum, FBS) in the sample was shown as non-influencing parameter in DoE setup. However, the separate experiment investigating only the FBS influence, and performed under other parameters optimally set, showed that FBS also influences the results of immunogenicity assay. Such finding indicated that (a) factors with strong influence on the measured outcome can hide the effects of parameters with modest/low influence and (b) the matrix of mumps virus samples to be compared for immunogenicity must be identical for reliable virus immunogenicity comparison. Finally the 3 mumps vaccine strains widely used for decades in the licensed vaccines were for the first time compared in an animal model, and results obtained were in line with their reported immunogenicity in human population supporting the predictive power of the optimized in vivo assay. PMID- 26376016 TI - Corrigendum. PMID- 26376017 TI - Corrigendum. PMID- 26376018 TI - Erratum. PMID- 26376019 TI - Usability test of a hand exoskeleton for activities of daily living: an example of user-centered design. AB - PURPOSE: (1) To assess a robotic device (Handexos) during the design process with regard to usability, end user satisfaction and safety, (2) to determine whether Handexos can improve the activities of daily living (ADLs) of spinal cord injury (SCI) patients and stroke patients with upper-limb dysfunction. METHODS: During a 2-year development stage of the device, a total of 37 participants (aged 22-68), 28 clinicians (experts) and nine patients with SCI or stroke (end users) were included in a user-centered design process featuring usability tests. They performed five grasps wearing the device. The assessments were obtained at the end of the session by filling out a questionnaire and making suggestions. RESULTS: The experts' opinion was that the modified device was an improvement over the preliminary version, although this was not reflected in the scores. Whereas end user scores for comfort, grasp, performance and safety were above the sufficiency threshold, the scores for year 2 were lower than those for year 1. CONCLUSIONS: The findings demonstrate that although Handexos meets the initial functional requirements and underlines the potential for assisting SCI and post stroke subjects in ADLs, several aspects such as mechanical complexity and low adaptability to different hand sizes need to be further addressed. Implications for Rehabilitation Wearable robotics devices could improve the activities of daily living in patients with spinal cord injury or stroke. They could be a tool for rehabilitation of the upper limb. Further usability tests to improve this type of tools are recommended. PMID- 26376020 TI - Bullying Victimization and Perpetration Among Adolescent Sport Teammates. AB - PURPOSE: Bullying is a specific pattern of repeated victimization explored with great frequency in school-based literature, but receiving little attention within sport. The current study explored the prevalence of bullying in sport, and examined whether bullying experiences were associated with perceptions about relationships with peers and coaches. METHOD: Adolescent sport team members (n = 359, 64% female) with an average age of 14.47 years (SD = 1.34) completed a pen and-paper or online questionnaire assessing how frequently they perpetrated or were victimized by bullying during school and sport generally, as well as recent experiences with 16 bullying behaviors on their sport team. Participants also reported on relationships with their coach and teammates. RESULTS: Bullying was less prevalent in sport compared with school, and occurred at a relatively low frequency overall. However, by identifying participants who reported experiencing one or more act of bullying on their team recently, results revealed that those victimized through bullying reported weaker connections with peers, whereas those perpetrating bullying only reported weaker coach relationships. CONCLUSION: With the underlying message that bullying may occur in adolescent sport through negative teammate interactions, sport researchers should build upon these findings to develop approaches to mitigate peer victimization in sport. PMID- 26376021 TI - The effect of Paget disease on axillary lymph node metastases and survival in invasive ductal carcinoma. AB - BACKGROUND: The objective of this study was to examine the effect of Paget disease (PD) on axillary lymph node metastases and survival in patients who had concomitant invasive ductal carcinoma (PD-IDC). METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify women who were diagnosed with PD-IDC from 2000 to 2011, comparing baseline demographic and tumor characteristics with those who were diagnosed with IDC alone during the same period. Multivariable logistic regression was used to examine the association of PD-IDC with axillary lymph node metastasis, and breast cancer-specific survival and overall survival were compared between the PD-IDC and IDC groups using the Kaplan-Meier method and Cox proportional hazards regression. RESULTS: The study cohort included 1102 patients with PD-IDC and 302,242 controls with IDC alone. PD IDC tumors were more likely to be centrally located (26.9% vs 5.5%; P < .001), high grade (63.5% vs 40.3%; P < .001), >2 cm in greatest dimension (47.1% vs 35.7%; P < .001), and estrogen/progesterone receptor-negative (45.2% vs 22.1%; P < .001). In adjusted analyses, patients with PD-IDC had higher odds of axillary lymph node metastasis (odds ratio, 1.83; P < .001). The unadjusted 10-year breast cancer-specific and overall survival rates were lower for the PD-IDC group compared with the IDC-alone group, although, after adjusting for disease stage, tumor characteristics, and local therapy, no significant differences in mortality risk were observed between the 2 groups (hazard ratio, 0.91; P = .24). CONCLUSIONS: PD-IDC is associated with an increased risk of axillary lymph node metastasis, but not with inferior survival, compared with IDC alone after adjustment for other disease factors. PMID- 26376022 TI - Analysis of polyethylene microplastics in environmental samples, using a thermal decomposition method. AB - Small polymer particles with a diameter of less than 5 mm called microplastics find their way into the environment from polymer debris and industrial production. Therefore a method is needed to identify and quantify microplastics in various environmental samples to generate reliable concentration values. Such concentration values, i.e. quantitative results, are necessary for an assessment of microplastic in environmental media. This was achieved by thermal extraction in thermogravimetric analysis (TGA), connected to a solid-phase adsorber. These adsorbers were subsequently analysed by thermal desorption gas chromatography mass spectrometry (TDS-GC-MS). In comparison to other chromatographic methods, like pyrolyse gas chromatography mass spectrometry (Py-GC-MS), the relatively high sample masses in TGA (about 200 times higher than used in Py-GC-MS) analysed here enable the measurement of complex matrices that are not homogenous on a small scale. Through the characteristic decomposition products known for every kind of polymer it is possible to identify and even to quantify polymer particles in various matrices. Polyethylene (PE), one of the most important representatives for microplastics, was chosen as an example for identification and quantification. PMID- 26376023 TI - Does Routine Imaging of Patients for Progression or Relapse Improve Survival in Rhabdomyosarcoma? AB - BACKGROUND: Patients with rhabdomyosarcoma (RMS) who complete therapy typically undergo 4 years of surveillance imaging despite lack of evidence that this improves outcomes. We compared overall survival (OS) between patients in whom progression or relapse was detected by routine clinical evaluation or by imaging. PROCEDURE: Children with progressive or relapsed RMS treated at Texas Children's Hospital between 1992 and 2012 were identified and their records were reviewed. Survival time after progression or relapse was compared between two groups: (1) patients in whom progression or relapse was suspected on the basis of clinical history, symptoms, laboratory evaluation, or physical exam; and (2) patients whose progression or relapse was initially detected by imaging. RESULTS: Of the 43 children with progressive or relapsed RMS, 26 (60%) had metastatic disease at diagnosis and 19 (44%) had alveolar histology. With a median follow up time of 5 years in six survivors, there was no difference in OS between patients in whom progression or relapse was diagnosed based on imaging (n = 15) or by clinical evaluation (n = 28) (3-year OS 20% vs. 11%, respectively, P = 0.38). Disease extent, primary site, and risk group at diagnosis were associated with survival after progression or relapse. CONCLUSIONS: Routine surveillance imaging practice should be critically reviewed for children with RMS. Although our findings must be validated by larger studies, they do have substantive implications. Reduced imaging tailored to the risk and pattern of recurrence, associated risks and cost could improve patient quality of life and decrease health-care expenditure without compromising outcome. PMID- 26376024 TI - Effect of shape, size, and aspect ratio on nanoparticle penetration and distribution inside solid tissues using 3D spheroid models. AB - Efficient penetration and uniform distribution of nanoparticles (NPs) inside solid tissues and tumors is paramount to their therapeutic and diagnostic success. While many studies have reported the effect of NP size and charge on intratissue distribution, role of shape, and aspect ratio on NP transport inside solid tissues remain unclear. Here experimental and theoretical studies are reported on how nanoscale geometry of Jet and Flash Imprint Lithography fabricated, polyethylene-glycol-based anionic nanohydrogels affect their penetration and distribution inside 3D spheroids, a model representing the intervascular region of solid, tumor-like tissues. Unexpectedly, low aspect ratio cylindrical NPs (H/D ~0.3; disk-like particles, 100 nm height, and 325 nm diameter) show maximal intratissue delivery (>50% increase in total cargo delivered) and more uniform penetration compared to nanorods or smaller NPs of the same shape. This is in contrast to spherical NPs where smaller NP size resulted in deeper, more uniform penetration. Our results provide fundamental new knowledge on NP transport inside solid tissues and further establish shape and aspect ratio as important design parameters in developing more efficient, better penetrating, nanocarriers for drug, or contrast-agent delivery. PMID- 26376025 TI - Subcutaneous L-tyrosine elicits cutaneous analgesia in response to local skin pinprick in rats. AB - The purpose of the study was to estimate the ability of L-tyrosine to induce cutaneous analgesia and to investigate the interaction between L-tyrosine and the local anesthetic lidocaine. After subcutaneously injecting the rats with L tyrosine and lidocaine in a dose-dependent manner, cutaneous analgesia (by blocking the cutaneous trunci muscle reflex-CTMR) was evaluated in response to the local pinprick. The drug-drug interaction was analyzed by using an isobolographic method. We showed that both L-tyrosine and lidocaine produced dose dependent cutaneous analgesia. On the 50% effective dose (ED50) basis, the rank of drug potency was lidocaine (5.09 [4.88-5.38] MUmol)>L-tyrosine (39.1 [36.5 41.8] MUmol) (P<0.05). At the equipotent doses (ED25, ED50, and ED75), the duration of cutaneous analgesia caused by L-tyrosine lasted longer than that caused by lidocaine (P<0.01). Lidocaine co-administered with L-tyrosine exhibited an additive effect on infiltrative cutaneous analgesia. Our pre-clinical study demonstrated that L-tyrosine elicits the local/cutaneous analgesia, and the interaction between L-tyrosine and lidocaine is additive. L-tyrosine has a lower potency but much greater duration of cutaneous analgesia than lidocaine. Adding L tyrosine to lidocaine preparations showed greater duration of cutaneous analgesia compared with lidocaine alone. PMID- 26376026 TI - The hypotensive effect of the nitric monoxide donor Oxacom at different routs of its administration to experimental animals. AB - Earlier it has been found that the hypotensive drug Oxacom containing binuclear dinitrosyl iron complexes (B-DNIC) with glutathione can effectively decrease, as a nitric monooxide (NO) donor, the mean arterial pressure (MAR) in rats upon intravenous bolus injection in the form of an aqueous solution (Chazov et al., 2012). The aim of this study was to investigate the hypotensive effects of Oxacom administered to experimental rats by intravenous, intramuscular, subcutaneous, intraperitoneal, intragastric, rectal routes.MAP and heart rate (HR) were measured with the help of arterial catheters equipped with tensometric sensors. Oxacom was administered to rats at the dose of 2.0 MUmole of B-DNIC/kg. The concentration of paramagnetic mononuclear protein-bound DNIC (M-DNIC) formed in the blood and tissues of various internal organs of the rat was determined by the EPR method. Upon subcutaneous, intramuscular or intraperitoneal administration of Oxacom, the maximum amplitude of the MAR decrease varies from 30% to 70%, respectively, in comparison with the corresponding parameter for the intravenously injected Oxacom. Another difference is the lack of the fast phase in the initial stage of the MAR decrease and the longer persistence of protein bound M-DNIC formed in the circulating blood after intramuscular, subcutaneous or intraperitoneal administration of Oxacom. Thus, the NO donor Oxacom exerts pronounced hypotensive effects on rats not only upon intravenous, but also upon intramuscular, subcutaneous or intraperitoneal administration. PMID- 26376027 TI - The gut microbial community in metabolic syndrome patients is modified by diet. AB - Intestinal microbiota changes may be involved in the development of metabolic syndrome (MetS), which is a multicomponent disorder frequently associated with obesity. The aim of this study was to test the effect of consuming two healthy diets: a Mediterranean diet and a low-fat high-carbohydrate diet, for 2years in the gut microbiota of MetS patients and those in the control group. We analyzed the differences in the bacterial community structure between the groups after 2years of dietary intervention (Mediterranean or low-fat diet) through quantitative polymerase chain reaction using primers, targeting specific bacterial taxa. We observed, at basal time, that the abundance of Bacteroides, Eubacterium and Lactobacillus genera is lower in the control group than in MetS patients, while Bacteroides fragilis group, Parabacteroides distasonis, Bacteroides thetaiotaomicron, Faecalibacterium prausnitzii, Fusobacterium nucleatum, Bifidobacterium longum, Bifidobacterium adolescentis, Ruminococcus flavefaciens subgroup and Eubacterium rectale are depleted in MetS patients (all P values <.05). Additionally, we found that long-term consumption of Mediterranean diet partially restores the population of P. distasonis, B. thetaiotaomicron, F. prausnitzii, B. adolescentis and B. longum in MetS patients (all P values <.05). Our results suggest that the Mediterranean diet could be a useful tool to restore potentially beneficial members of the gut microbiota, although the stability of these changes over time still remains to be assessed. PMID- 26376028 TI - Interviewing a Silent (Radioactive) Witness through Nuclear Forensic Analysis. AB - Nuclear forensics is a relatively young discipline in science which aims at providing information on nuclear material of unknown origin. The determination of characteristic parameters through tailored analytical techniques enables establishing linkages to the material's processing history and hence provides hints on its place and date of production and on the intended use. PMID- 26376029 TI - "Just Because It's Out There, People Aren't Going to Use It." HIV Self-Testing Among Young, Black MSM, and Transgender Women. AB - HIV disproportionately affects young black MSM and transgender women in the US. Increasing HIV testing rates among these populations is a critical public health goal. Although HIV self-tests are commercially available, there is a need to better understand access to and uptake of HIV self-testing among this population. Here, we report results of a qualitative study of 30 young black MSM and transgender women residing in the New York City area to understand facilitators of and barriers to a range of HIV testing approaches, including self-testing. Mean age was 23.7 years (SD = 3.4). Over half (54%) had some college or an associate's degree, yet 37% had an annual personal income of less than $10,000 per year. Most (64%) participants had tested in the past 6 months; venues included community health/free clinics, medical offices, mobile testing units, hospitals, emergency departments, and research sites. Just one participant reported ever using a commercially available HIV self-test. Facilitators of self testing included convenience, control, and privacy, particularly as compared to venue-based testing. Barriers to self-testing included the cost of the test, anxiety regarding accessing the test, concerns around correct test operation, and lack of support if a test result is positive. Participants indicated that instruction in correct test operation and social support in the event of a positive test result may increase the likelihood that they would use the self test. Alongside developing new approaches to HIV prevention, developing ways to increase HIV self-testing is a public health priority for young, black MSM, and transgender women. PMID- 26376036 TI - Typical Brake Reaction Times Across the Life Span. AB - This paper provides average brake reaction times for healthy community living adults from 16 to 90+ years of age, divided by gender. Using consistent directions and context, the RT-2S Simple Brake Reaction shows that average brake reactions for males is 0.50 seconds (median = 0.48, minimum = 0.25 maximum = 0.92) and for females is 0.53 seconds (median = 0.51 minimum = 0.30 maximum = 1.36). The use of a brake reaction timer to assess fitness to drive may be useful for clients recovering from orthopedic surgery, while use as a driving determinate of older adults should be done in conjunction with other tools. PMID- 26376030 TI - Remote Sonography in Routine Clinical Practice Between Two Isolated Medical Centers and the University Hospital Using a Robotic Arm: A 1-Year Study. AB - BACKGROUND: A robotic arm was developed by our laboratory for tele-operated echography on patients in locations isolated from a trained sonographer. The objective of the study was to evaluate, over a 1-year period, the use of the robotic arm for telesonography performed by a sonographer located at the University Hospital (Tours, France) on patients in two isolated medical centers 50 km away linked via the Internet. MATERIALS AND METHODS: A nonsonographer operator (physician or paramedic) located the ultrasound probe attached to the robotic arm over the appropriate acoustic window for the organ of interest by rolling the whole robotic arm and mechanical support across the floor. The expert sonographer then telemanipulated the robotic arm via an Internet connection and adjusted the orientation of the probe until the most appropriate organ view for delivering a diagnosis was obtained. RESULTS: Three hundred telesonography examinations were performed within 1 year: 68 (22.7%) on abdominal organs, 20 (6.7%) on pelvic organs, 138 (46%) on supraaortic vessels (carotid artery), 33 (11%) on the thyroid, 30 (10%) on leg veins, and 11 (3.7%) on the kidney and urinary tract. Telesonography could not be achieved in 10 of the 300 cases due to poor image quality on obese patients or those presenting poor echogenicity. These cases were re-examined at the university hospital by a sonographer. The rate of telesonography exams over the 1-year period was 1.5 per day for the "general population" medical site and 1 per week for the "elderly patient" medical site. CONCLUSIONS: This study demonstrated that telesonography using a robotic arm can be routinely used for providing echographic diagnoses on patients isolated from imaging centers. PMID- 26376037 TI - Clinical utility of automated chemiluminescent antiphospholipid antibody assay. AB - BACKGROUND: The threshold for clinically relevant levels of antiphospholipid (aPL) antibodies for the diagnosis of antiphospholipid syndrome (APS) remains a matter of debate. As new technologies for antibody detection are introduced, their performance characteristics must be clearly understood and compared to traditional assays. OBJECTIVES: To assess the analytical performance and clinical utility of fully automated anticardiolipin (aCL) and anti-beta2 glycoprotein I (abeta2GPI) chemiluminescent immunoassays (CIA) in comparison to the traditional ELISA tests. PATIENTS/METHODS: Samples from 220 autoimmune patients were studied (primary APS - 74; secondary APS - 47, systemic lupus erythematosus (SLE) without APS - 99). All samples were tested for IgG and IgM aCL and beta2GPI antibodies using both CIA and ELISA, and for lupus anticoagulant (LAC). RESULTS: Good qualitative agreement and quantitative correlation were found between methods in regard to individual antibodies and their categories (profiles). All assays showed good clinical performance in APS, and strong correlation with APS-related clinical symptoms. Importance of determining individual laboratory 99 percentile values for a healthy population as normal cut-off values was shown. Additionally, based on a clinical approach, this study has established the low/medium threshold for QUANTA Flash aCL IgG and IgM assays. CONCLUSIONS: This study showed good clinical performance and strong correlation of the new automated CIA aPL assays with APS clinical symptoms. It also enabled us to determine the corresponding low/medium antibody threshold for the aCL antibody methods with different unit types. PMID- 26376038 TI - History of deep vein thrombosis is a discriminator for concomitant atrial fibrillation in pulmonary embolism. AB - BACKGROUND: Pulmonary embolism (PE) is the consequence of deep vein thrombosis (DVT) in 70% of all cases. Although, PE and DVT are commonly related to risk factors of Virchow's triad, both entities are linked to cardiovascular risk factors, but risk factors seem differently important in both entities. OBJECTIVES: We aimed to investigate clinical profile and outcome of patients with PE history stratified by concomitant DVT. PATIENTS/METHODS: Data from the observational multi-center thrombEVAL-study were analyzed. RESULTS: The sample (N=2,318) comprised 295 PE patients, of whom 69.2% (N=204) had DVT. Individuals without DVT were older and had higher prevalence of concomitant atrial fibrillation (AF), chronic lung diseases, coronary artery disease, heart failure and hypertension. Multivariable regression revealed an independent association of AF (Odds Ratio (OR) 3.17, 95% CI 1.63-6.18, P<0.001) and coronary artery disease (OR 2.31, 95% CI 1.15-4.66, P=0.019) with PE without DVT. There was higher frequency of permanent AF in individuals without DVT, whereas paroxysmal AF was more prevalent in individuals with DVT. All AF subtypes were independently associated with PE without DVT with increasing ORs from paroxysmal to permanent AF. PE patients with and without DVT did not differ in survival (P=0.32) and cost relevant clinical outcome (P=0.26) during follow-up. AF in PE patients was associated with cost-relevant clinical outcome (Hazard Ratio (HR) 1.78, 95% CI 1.03-3.09, P=0.040), but no significant difference in survival (HR 0.93, 95% CI 0.35-2.50, P=0.88) was observed. CONCLUSIONS: History of DVT is a significant discriminator for clinical profile of PE patients. Individuals without DVT had more often cardiac and pulmonary disease with strongest association with AF. Data advocate a potential link between AF and PE. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov, Unique identifier NCT01809015. PMID- 26376040 TI - Long faun tail: a rare cutaneous marker of spinal dysraphism. PMID- 26376039 TI - A current and historical perspective on disparities in US childhood pneumococcal conjugate vaccine adherence and in rates of invasive pneumococcal disease: Considerations for the routinely-recommended, pediatric PCV dosing schedule in the United States. AB - Previous research has suggested that reducing the US 4-dose PCV13 schedule to a 3 dose schedule may provide cost savings, despite more childhood pneumococcal disease. The study also stressed that dose reduction should be coupled with improved PCV adherence, however, US PCV uptake has leveled-off since 2008. An estimated 24-36% of US children aged 5-19 months are already receiving a reduced PCV schedule (i.e., missing >=1 dose). This raises a practical concern that, under a reduced, 3-dose schedule, a similar proportion of children may receive <=2 doses. It is also unknown if a reduced, 3-dose PCV schedule in the United States will afford the same disease protection as 3-dose schedules used elsewhere, given lower US PCV adherence. Finally, more assurance is needed that, under a reduced schedule, racial, socioeconomic, and geographic disparities in PCV adherence will not correspond with disproportionately higher rates of pneumococcal disease among poor or minority children. PMID- 26376041 TI - Cardiac involvement in cutaneous sarcoidosis: case reports and review of the literature. AB - AIM: Sarcoidosis is a chronic multisystem disease that usually has a good prognosis but in some cases, especially when cardiac involvement occurs, the outcome is fatal. Cardiac sarcoidosis is insidious to diagnose because it is usually asymptomatic and when clinically apparent, it may have a wide variety of manifestations. The aim of this study was to investigate the possible cardiac involvement in cutaneous sarcoidosis patients. METHODS: Diagnosis of cutaneous sarcoidosis was confirmed by skin biopsy, laboratory tests and radiological findings in 13 Caucasian Patients. To evaluate cardiac damage, Electrocardiogram, echocardiography and contrast-enhanced cardiac magnetic resonance were performed. RESULTS: Magnetic resonance identified cardiac sarcoidosis only in one of the cutaneous sarcoidosis patients. CONCLUSIONS: We suggest to investigate cardiac involvement in patients with cutaneous sarcoidosis, even if asymptomatic, since cardiac lesions are frequently associated with a poorer prognosis. PMID- 26376042 TI - Electrochemotherapy in non-melanoma head and neck skin cancers: a three-center experience and review of the literature. AB - BACKGROUND: The main purposes of this study were to evaluate the efficacy of electrochemotherapy in head and neck tumors, to assess local tumor control, its safety profile and its impact on the patients' quality of life. METHODS: This is a multicenter prospective, non-randomized phase II trial. This trial was carried out at the Dermatology Clinic of the "Sapienza" University of Rome, at the Dermatology Clinic of the University of Chieti and at the Dermatology Clinic of the University of Turin. Fifty-five patients with head and neck cancer were recruited. Electrochemotherapy was carried out according to the ESOPE guidelines. Statistical analyses were performed using Stata/SE v.12.0 Statistical Software. RESULTS: A significant clinical response was achieved in 50/55 patients with 91% of objective response rate (OR). Thirty-three out of 55 patients showed a complete response (CR) (60%); 17 treated patients had a partial response (PR) (31%). A significantly higher CR rate was obtained in patients not previously treated by surgery (15/19; 79%), with respect to those with a previous excision of the tumor (14/30; 47%) (P=0.025). An additional parameter influencing response is represented by anesthesia: patients treated by ECT with general anesthesia were characterized by significantly higher CR rate (68%) than those treated with local anesthesia (27%) (P=0.014). CONCLUSIONS: Our experience confirmed high efficiency in local tumor control, excellent toxicity profile, tissue preservation with good cosmetic and functional results, even with repeated applications. ECT can represent a first-line treatment in the local management of head and neck cancers. PMID- 26376044 TI - Politics and Universal Health Coverage--The Post-2015 Global Health Agenda. AB - What political, social, and economic factors allow a movement toward universal health coverage to take hold in some low- and middle-income countries? Can we use that knowledge to help other such countries achieve health care for all? PMID- 26376045 TI - Shifting to Sustainable Development Goals--Implications for Global Health. PMID- 26376046 TI - Experimental investigation of the effect of occupant characteristics on contemporary seat belt payout behavior in frontal impacts. AB - OBJECTIVE: The goal of this study was to investigate the influence of the occupant characteristics on seat belt force vs. payout behavior based on experiment data from different configurations in frontal impacts. METHODS: The data set reviewed consists of 58 frontal sled tests using several anthropomorphic test devices (ATDs) and postmortem human subjects (PMHS), restrained by different belt systems (standard belt, SB; force-limiting belt, FLB) at 2 impact severities (48 and 29 km/h). The seat belt behavior was characterized in terms of the shoulder belt force vs. belt payout behavior. A univariate linear regression was used to assess the factor significance of the occupant body mass or stature on the peak tension force and gross belt payout. RESULTS: With the SB, the seat belt behavior obtained by the ATDs exhibited similar force slopes regardless of the occupant size and impact severities, whereas those obtained by the PMHS were varied. Under the 48 km/h impact, the peak tension force and gross belt payout obtained by ATDs was highly correlated to the occupant stature (P =.03, P =.02) and body mass (P =.05, P =.04), though no statistical difference with the stature or body mass were noticed for the PMHS (peak force: P =.09, P =.42; gross payout: P =.40, P =.48). With the FLB under the 48 km/h impact, highly linear relationships were noticed between the occupant body mass and the peak tension force (R(2) = 0.9782) and between the gross payout and stature (R(2) = 0.9232) regardless of the occupant types. CONCLUSIONS: The analysis indicated that the PMHS characteristics showed a significant influence on the belt response, whereas the belt response obtained with the ATDs was more reproducible. The potential cause included the occupant anthropometry, body mass distribution, and relative motion among body segments specific to the population variance. This study provided a primary data source to understand the biomechanical interaction of the occupant with the restraint system. Further research is necessary to consider these effects in the computational studies and optimized design of the restraint system in a more realistic manner. PMID- 26376047 TI - Comparing Current Practice to Recommendations for the Child and Adult Care Food Program. AB - BACKGROUND: The federal Child and Adult Care Food Program (CACFP) assists child care centers serving low-income preschoolers and regulates the quality and quantity of food served. The aim of this study was to assess the nutritional quality of lunches served at 38 child care centers and examine how current practices compare to proposed meal pattern recommendations. METHODS: Preschool aged children (n = 204) were observed eating lunch in 38 CACFP-participating preschools. All foods served and consumed were measured and compared to the 2011 Institute of Medicine (IOM) recommendations to improve CACFP and the 2015 Proposed Rule issued by the USDA. RESULTS: All centers provided access to all required lunch components, but not all components were served (i.e., placed on the child's plate). Vegetables were significantly less likely to be served than meat or grains. Compared with CACFP recommended portion sizes, servings of meat and grain were high, whereas milk was low. Compared with IOM recommendations, average calorie consumption was appropriate, but saturated fat, protein, and sodium intake were high and dietary fiber was low. Meals that offered children both a fruit and a vegetable led to significantly higher produce consumption than meals that offered only one fruit or one vegetable. CONCLUSIONS: Child care centers generally comply with current CACFP regulations, but do not provide lunches consistent with the 2011 IOM recommendations for saturated fat, protein, fiber, and sodium. Decreased use of beef and cheese and increased provision of whole grains, fruits, and vegetables are recommended. PMID- 26376048 TI - The feasibility and acceptability of questionnaires and accelerometry for measuring physical activity and sedentary behaviour in adults with mental illness. AB - BACKGROUND: Adults with mental illness may have difficulties with data collection methods such as questionnaires and accelerometry. AIMS: To assess the utility of questionnaires and accelerometry for assessing physical activity (PA) and sedentary behaviour (SB) in non-institutionalised adults with mental illness. METHODS: Participants were recruited from outpatient clinics and community organisations. Participants completed PA and SB questionnaires, wore accelerometers for 7 d, and rated the ease/difficulty of completing study components. Recruitment numbers, adherence, and ease/difficulty ratings were examined. Ease/difficulty ratings were compared between study components, and between participants by distress level. RESULTS: One hundred forty-two participants completed the questionnaires; they found it easier to report PA than reclining time (p = 0.017), and reclining time than sitting time (p < 0.001). Participants with high distress found it more difficult to report sitting time and PA than participants with low distress (p < 0.017). Ninety-nine participants (70%) completed the accelerometry; the majority (88%) met the minimum wear-time criteria. They found it easier to wear the monitor during the day than while sleeping (p < 0.001), and easier to complete accelerometry than questionnaires (p < 0.001). CONCLUSIONS: Accelerometry was more feasible for assessing SB than questionnaires. Questionnaires were feasible for assessing PA, but less acceptable for people experiencing high distress. PMID- 26376049 TI - Neuroimmune Control of Acute Kidney Injury and Inflammation. AB - Despite major advances in identifying pathophysiological mechanisms of acute kidney injury (AKI), no definitive therapeutic or preventive modalities have been developed with the exception of dialysis. One possible approach is the control of inflammation and AKI through activation of the neuroimmune axis. The cholinergic anti-inflammatory pathway is thought to contribute to the homeostatic response in inflammation-related disorders and forms the basis for recent approaches toward therapeutic intervention. The concept is based on the emerging understanding of the interface between the nervous and immune systems. In the cholinergic anti inflammatory pathway, the efferent vagus nerve indirectly stimulates the CD4+ T cells in the spleen. The CD4+ T-cells produce acetylcholine, which stimulates alpha 7 nicotinic receptors (alpha7nAChRs) on macrophages. Activation of the alpha7nAChRs on macrophages in turn activates NF-x03BA;beta and elicits an anti inflammatory response. Recently, we demonstrated the effect of a non pharmacologic, noninvasive, ultrasound-based method to prevent renal ischemia reperfusion injury and sepsis-induced AKI in mice. Our data suggest that ultrasound-induced tissue protection is mediated through the activation of the cholinergic anti-inflammatory pathway. In addition, nicotinic receptor agonists and ghrelin, a neuropeptide, were reported to prevent AKI possibly through a mechanism closely linked with the stimulation of the vagus nerve. Based on the studies focusing on inflammation and the observations regarding kidney injury, we believe that activating the cholinergic anti-inflammatory pathway will be a new modality for the prevention and treatment of AKI. PMID- 26376050 TI - Shift Work and Obesity among Canadian Women: A Cross-Sectional Study Using a Novel Exposure Assessment Tool. AB - BACKGROUND/OBJECTIVES: It has been suggested that the association between shift work and chronic disease is mediated by an increase in obesity. However, investigations of the relationship between shift work and obesity reveal mixed findings. Using a recently developed exposure assessment tool, this study examined the association between shift work and obesity among Canadian women from two studies: a cohort of university alumni, and a population-based study. METHODS: Self-administered questionnaire data were used from healthy, currently employed females in a population-based study, the Ontario Women's Diet and Health case-control study (n = 1611 controls), and from a subset of a of university alumni from the Canadian Study of Diet, Lifestyle, and Health (n = 1097) cohort study. Overweight was defined as BMI>=25 to <30, and obesity as BMI>=30. Reported occupation was converted to occupational codes and linked to a probability of shift work value derived from Survey of Labour and Income Dynamics data. Regular evenings, nights, or rotating work comprised shift work. Polytomous logistic regression estimated the association between probability of shift work, categorized as near nil, low, medium, and high probability of shift work, on overweight and obesity, controlling for detected confounders. RESULTS: In the population-based sample, high probability of shift work was associated with obesity (reference = near nil probability of shift work, OR: 1.88, 95% CI: 1.01 3.51, p = 0.047). In the alumni cohort, no significant association was detected between shift work and overweight or obesity. CONCLUSIONS: As these analyses found a positive association between high probability of shift work exposure and obesity in a population-based sample, but not in an alumni cohort, it is suggested that the relationship between shift work and obesity is complex, and may be particularly susceptible to occupational and education-related factors within a given population. PMID- 26376051 TI - Association of serum brain-derived neurotrophic factor (BDNF) and tumor necrosis factor-alpha (TNF-alpha) with diagnosis of delirium in oncology inpatients. AB - OBJECTIVE: To evaluate brain-derived neurotrophic factor (BDNF) and tumor necrosis factor-alpha (TNF-alpha) blood levels as disease biomarkers of delirium in oncology inpatients. METHODS: Seventeen oncology inpatients with delirium, 28 oncology inpatients without delirium, and 25 non-oncology controls (caregivers) were consecutively recruited from a Brazilian cancer center. This sample was matched by age, sex, and education level. The Confusion Assessment Method, the Mini-Mental State Examination, and the Digit Span Test were administered to ascertain delirium diagnosis. BDNF and TNF-alpha levels were measured by the Sandwich-ELISA method and flow cytometry, respectively. Blood samples were collected immediately after clinical evaluation. RESULTS: Oncology inpatients (with and without delirium) showed significantly lower BDNF levels compared with non-oncology controls (F = 13.830; p = 0.001). TNF-alpha levels did not differ between the three groups. CONCLUSION: A cross-sectional relationship of BDNF and TNF-alpha blood levels with delirium in oncology inpatients was not demonstrated. The association between cancer and reduced serum BDNF levels may be mediated by confounding factors. PMID- 26376052 TI - Religious coping and its influence on psychological distress, medication adherence, and quality of life in inflammatory bowel disease. AB - OBJECTIVE: Inflammatory bowel disease (IBD) is associated with elevated levels of anxiety and depression and a reduction in health-related quality of life (HRQoL). Nonadherence to treatment is also frequent in IBD and compromises outcomes. Religious coping plays a role in the adaptation to several chronic diseases. However, the influence of religious coping on IBD-related psychological distress, HRQoL, and treatment adherence remains unknown. METHOD: This cross-sectional study recruited 147 consecutive patients with either Crohn's disease or ulcerative colitis. Sociodemographic data, disease-related variables, psychological distress (Hospital Anxiety and Depression Scale), religious coping (Brief RCOPE Scale), HRQoL (WHOQOL-Bref), and adherence (8-item Morisky Medication Adherence Scale) were assessed. Hierarchical multiple regression models were used to evaluate the effects of religious coping on IBD-related psychological distress, treatment adherence, and HRQoL. RESULTS: Positive RCOPE was negatively associated with anxiety (b = 0.256; p = 0.007) as well as with overall, physical, and mental health HRQoL. Religious struggle was significantly associated with depression (b = 0.307; p < 0.001) and self-reported adherence (b = 0.258; p = 0.009). Finally, anxiety symptoms fully mediated the effect of positive religious coping on overall HRQoL. CONCLUSION: Religious coping is significantly associated with psychological distress, HRQoL, and adherence in IBD. PMID- 26376053 TI - Motor development of children with attention deficit hyperactivity disorder. AB - OBJECTIVE: To compare both global and specific domains of motor development of children with attention deficit hyperactivity disorder (ADHD) with that of typically developing children. METHODS: Two hundred children (50 children with clinical diagnoses of ADHD, according to the DSM-IV-TR and 150 typically developing controls), aged 5 to 10 years, participated in this cross-sectional study. The Motor Development Scale was used to assess fine and global motricity, balance, body schema, and spatial and temporal organization. RESULTS: Between group testing revealed statistically significant differences between the ADHD and control groups for all domains. The results also revealed a deficit of nearly two years in the motor development of children with ADHD compared with the normative sample. CONCLUSION: The current study shows that ADHD is associated with a delay in motor development when compared to typically developing children. The results also suggested difficulties in certain motor areas for those with ADHD. These results may point to plausible mechanisms underlying the relationship between ADHD and motor difficulties. PMID- 26376054 TI - Epistasis between COMT Val158Met and DRD3 Ser9Gly polymorphisms and cognitive function in schizophrenia: genetic influence on dopamine transmission. AB - OBJECTIVE: To assess the relationship between cognitive function, a proposed schizophrenia endophenotype, and two genetic polymorphisms related to dopamine function, catechol-O-methyl transferase (COMT) Val158Met and dopamine receptor 3 (DRD3) Ser9Gly. METHODS: Fifty-eight outpatients with schizophrenia/schizoaffective disorder and 88 healthy controls underwent neurocognitive testing and genotyping. Analyses of covariance (ANCOVAs) using age, sex, and years of education as covariates compared cognitive performance for the proposed genotypes in patients and controls. ANCOVAs also tested for the epistatic effect of COMT and DRD3 genotype combinations on cognitive performance. RESULTS: For executive functioning, COMT Val/Val patients performed in a similar range as controls (30.70-33.26 vs. 35.53-35.67), but as COMT Met allele frequency increased, executive functioning worsened. COMT Met/Met patients carrying the DRD3 Ser/Ser genotype performed poorest (16.184 vs. 27.388-31.824). Scores of carriers of this COMT/DRD3 combination significantly differed from all DRD3 Gly/Gly combinations (p < 0.05), from COMT Val/Met DRD3 Ser/Gly (p = 0.02), and from COMT Val/Val DRD3 Ser/Ser (p = 0.01) in patients. It also differed significantly from all control scores (p < 0.001). CONCLUSION: Combined genetic polymorphisms related to dopamine neurotransmission might influence executive function in schizophrenia. Looking at the effects of multiple genes on a single disease trait (epistasis) provides a comprehensive and more reliable way to determine genetic effects on endophenotypes. PMID- 26376055 TI - Impulsivity and compulsive buying are associated in a non-clinical sample: an evidence for the compulsivity-impulsivity continuum? AB - OBJECTIVE: Compulsive buying is controversial in clinical psychiatry. Although it is defined as an obsessive-compulsive disorder, other personality aspects besides compulsivity are related to compulsive buying. Recent studies suggest that compulsivity and impulsivity might represent a continuum, with several psychiatric disorders lying between these two extremes. In this sense, and following the perspective of dimensional psychiatry, symptoms of impulsivity and compulsivity should correlate even in a non-clinical sample. The present study aims to investigate whether these two traits are associated in a healthy adult sample. METHODS: We evaluated 100 adults, with no self-reported psychiatric disorders, using the Barratt Impulsiveness Scale-11 and two scales of compulsive buying. RESULTS: Using multiple linear regressions, we found that impulsivity accounted for about 15% of variance in the compulsive-buying measure. CONCLUSIONS: Our results suggest that an association between impulsivity and compulsive buying occurs even in non-clinical samples, evidence that compulsivity and impulsivity might form a continuum and that compulsive buying might be an intermediate condition between these two personality traits. PMID- 26376056 TI - Normative data of the Barratt Impulsiveness Scale 11 (BIS-11) for Brazilian adults. AB - OBJECTIVE: The Barratt Impulsiveness Scale (BIS-11) is a valid and reliable instrument, and one of the most often used tools to assess impulsivity. This study assesses the performance of a large sample of adults by using a version of BIS-11 adapted to Brazilian Portuguese. METHODS: We assessed 3,053 adults from eight Brazilian states. Internal consistencies and performance data were presented for two correction criteria of BIS-11: original and the two-factor score. RESULTS: The associations between age, sex, region, and education and the BIS-11 scores present very small effect sizes. Therefore, we provided a percentile rank parameter for the different BIS-11 subscores considering the whole sample. Given the internal consistency of the two correction systems, we found that only the two-factor system fulfills the psychometric criteria of Cronbach's alpha (cutoff value of at least 0.6). CONCLUSION: Our results support the use of the Brazilian adaptation of BIS-11 in different regions of the country as a measure of impulsivity. Since high impulsiveness is a characteristic of several dysfunctional behaviors, the establishment of normative parameters is of utmost relevance and should be extended to other age ranges and populations in future studies. PMID- 26376057 TI - Functional capacity: a new framework for the assessment of everyday functioning in schizophrenia. AB - Historically, measures of everyday functioning have focused exclusively on real world performance. Despite the unquestionable value of "real-world functioning", it has become clear that instruments for its assessment might not be as accurate as desirable. Functional capacity is a domain of everyday functioning that can be assessed through performance-based measures. In the last decade, functional capacity has become a cornerstone for the assessment of everyday functioning, since, alongside measures of real-world functioning, it provides a much more comprehensive picture of functional outcomes than any measurement alone. Functional capacity is more stable and less vulnerable to influence from environmental factors than other domains, and its correlation with cognitive functions has encouraged the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) project to suggest that a performance-based measure of functional capacity be included as a co-primary assessment of cognition in clinical trials. Functional capacity assessment instruments may be also useful in the evaluation of remission in schizophrenia. Validation of these instruments in different countries is desirable, and should always include cross cultural adaptation; within large countries, adjustment for regional variations should be considered. PMID- 26376058 TI - Weighing the evidence for suicide prevention. PMID- 26376059 TI - Crack-cocaine addiction in an indigenous Brazilian: a case report. PMID- 26376061 TI - Medical and societal aspects of alcohol consumption in Russia. PMID- 26376060 TI - Prevalence of self-injurious behavior in people with intellectual development disorder. PMID- 26376062 TI - Intensive care unit capacity strain and adherence to prophylaxis guidelines. AB - PURPOSE: The purpose of the study is to examine the relationship between different measures of capacity strain and adherence to prophylaxis guidelines in the intensive care unit (ICU). MATERIALS AND METHODS: We conducted a retrospective cohort study within the Project IMPACT database. We used multivariable logistic regression to examine relationships between ICU capacity strain and appropriate usage of venous thromboembolism prophylaxis (VTEP) and stress ulcer prophylaxis (SUP). RESULTS: Of 776,905 patient-days eligible for VTEP, appropriate therapy was provided on 68%. Strain as measured by proportion of new admissions (odds ratio [OR], 0.91; 95% confidence interval [CI], 0.90 0.91) and census (OR, 0.97; 95% CI, 0.97-0.98) was associated with decreased odds of receiving VTEP. With increasing strain as measured by new admissions, the degradation of VTEP utilization was more severe in ICUs with closed (OR, 0.85; 95% CI, 0.83-0.88) than open (OR, 0.91; 95% CI, 0.91-0.92) staffing models (interaction P<.001). Of 185425 patient-days eligible for SUP, 48% received appropriate therapy. Administration of SUP was not significantly influenced by any measure of strain. CONCLUSIONS: Rising capacity strain in the ICU reduces the odds that patients will receive appropriate VTEP but not SUP. The variability among different types of ICUs in the extent to which strain degraded VTEP use suggests opportunities for systems improvement. PMID- 26376065 TI - Effects of the Advanced Innovative Internet-Based Communication Education Program on Promoting Communication Between Nurses and Patients With Dementia. AB - BACKGROUND: Effective communication between nurses and patients with dementia promotes the quality of patient care by improving the identification of patient needs and by reducing the miscommunication-related frustration of patients and nurses. PURPOSE: This study evaluates the effects of an advanced innovative Internet-based communication education (AIICE) program on nurses' communication knowledge, attitudes, frequency of assessing patient communication capacity, and communication performance in the context of care for patients with dementia. In addition, this study attempts to evaluate the indirect effects of this program on outcomes for patients with dementia, including memory and behavior-related problems and depressive symptoms. METHODS: A quasi-experimental research design with a one-group repeated measure was conducted. Convenience sampling was used to recruit nurses from long-term care facilities in southern Taiwan. Data were analyzed using general estimating equations to compare changes over time across three points: baseline, fourth-week posttest, and 16th-week posttest. One hundred five nurses completed the AIICE program and the posttest surveys. RESULTS: The findings indicate that nurses' communication knowledge, frequency in assessing patients' communication capacity, and communication performance had improved significantly over the baseline by either the 4th- or 16th-week posttest (p < .01). However, communication attitude showed no significant improvement in the posttest survey (p = .40). Furthermore, the findings indicate that the memory and behavior-related problems and the depressive symptoms of patients had decreased significantly by the 16th-week posttest (p = .05). CONCLUSIONS/IMPLICATIONS FOR PRACTICE: This study showed that the AIICE program improves nurses' communication knowledge, frequency to assess patients' communication capacity, and communication performance and alleviates the memory and behavior-related problems and depressive symptoms of patients. The continuous communication training of nurses using the AIICE program is thus recommended. PMID- 26376064 TI - Professional Practice Environment Scale-Chinese Version: Development and Psychometric Testing. AB - BACKGROUND: The Professional Practice Environment (PPE) scale is widely used to assess the quality of the healthcare environment around the world. No validated Chinese-language scale that is designed to address this issue currently exists. PURPOSE: The present study evaluates the construct validity of the Chinese version PPE on a sample of 290 healthcare workers in Taiwan. METHODS: Forward and backward translations of the PPE scale of Halcomb et al. were used to ensure semantic equivalence. Further, multiple psychometric properties were examined. RESULTS: The developed scale showed sufficient equivalence. The results of a survey of 290 healthcare providers demonstrated that the developed Chinese version PPE scale had high reliability (Cronbach's alpha = .88) and validity. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The findings of the present study support the effectiveness and efficiency of the Chinese-version 30-item Halcomb's PPE in assessing the professional practice environment in Taiwan. PMID- 26376066 TI - Coxiella burnetii seropositivity and associated risk factors in sheep in Ontario, Canada. AB - Coxiella burnetii is a zoonotic bacterium that can cause abortion in sheep in late gestation, as well as the delivery of stillborn, and non-viable lambs (Rodolakis, 2006). A cross-sectional study was conducted in Ontario, Canada, to investigate C. burnetii exposure in sheep. Between August 2010 and January 2012, sera from 2363 reproductively active ewes from 72 farms were tested for C. burnetii specific antibodies using the CHEKIT Q fever ELISA Test kit (IDEXX Laboratories). Overall, exposure was common; sheep-level seroprevalence was 14.7% (347/2363, 95% CI: 13.3-16.2), and was higher in dairy sheep (24.3%, 181/744) than meat sheep (10.2%, 166/1619) (p<0.0001). At the farm-level, 48.6% (35/72, 95% CI: 37.2-60.1) of farms had at least one seropositive sheep. A mixed multivariable logistic model that controlled for farm-level clustering, identified risk factors associated (p<0.05) with sheep seropositivity. Increasing female flock size (logarithmic scale) was associated with increased odds of seropositivity. By way of illustration, increasing the female flock size from 100 to 200 increased the odds of seropositivity by 2.26 times (95% CI: 1.5-3.5). Sheep that lambed in an airspace separate from the flock had 11.3 times (95% CI: 2.9-43.6) the odds of seropositivity relative to other sheep. The practice of loaning sheep that returned to the farm increased odds of seropositivity by 8.1 times (95% CI: 1.8-33.6). Lambing pen hygiene practices also influenced odds of seropositivity. Relative to sheep from farms where all lambing pen hygiene measures were practiced after lambing (i.e., adding bedding, removing birth materials and disinfection), sheep from farms that only added bedding, or those that just added bedding and removed birthing materials had 5.9 times (95% CI: 1.1 32.1) and 9.0 times (95% CI: 2.2-36.9) the odds of seropositivity, respectively. These results can be used to inform prevention and control strategies with the aim of reducing C. burnetii exposure in sheep. PMID- 26376067 TI - A novel mutation of GATA4 (K300T) associated with familial atrial septal defect. AB - The GATA-binding protein 4 gene (GATA4) encodes a zinc-finger transcription factor that plays a key role in embryogenesis and cardiac development. Variants in the GATA4 gene have been implicated in several congenital heart diseases (CHD), such as the tetralogy of Fallot (ToF), atrial septal defect (ASD), ventricular septal defect (VSD), atrioventricular septal defect (AVSD), and dilated cardiomyopathy (DCM). We studied a four-generation Chinese ASD family and identified a novel GATA4 mutation (c.A899C, p.K300T) in all surviving affected members and two carriers with incomplete penetrance. Bioinformatics programs (PolyPhen-2, SIFT, and MutationTaster) predicted the mutation to be deleterious. The lysine at the mutation position was highly conserved from Drosophila to humans and was recognized as a methylation location in the GATA4 protein. The involvement of the lysine methylation in cardiogenesis by attenuating the transcriptional activity of GATA4 in mice has been previously examined. Our study broadens the mutation spectrum of the GATA4 gene and reveals for the first time a mutation at the methylation position of GATA4 associated with ASD. PMID- 26376068 TI - Genetic diversity analysis of buffalo fatty acid synthase (FASN) gene and its differential expression among bovines. AB - Fatty Acid Synthase (FASN) gene seems to be structurally and functionally different in bovines in view of their distinctive fatty acid synthesis process. Structural variation and differential expression of FASN gene is reported in buffalo (Bubalus bubalis), a bovine species close to cattle, in this study. Amino acid sequence and phylogenetic analysis of functionally important thioesterase (TE) domain of FASN revealed its conserved nature across mammals. Amino acid residues at TE domain, responsible for substrate binding and processing, were found to be invariant in all the mammalian species. A total of seven polymorphic nucleotide sites, including two in coding region of TE domain were identified across the 10 buffalo populations of riverine and swamp types. G and C alleles were found almost fixed at g18996 and g19056 loci, respectively in riverine buffaloes. Principal component analysis of three SNPs (g18433, g18996 and g19056) revealed distinct classification of riverine and swamp buffalo populations. Reverse Transcription-PCR amplification of mRNA corresponding to exon 8-10 region of buffalo FASN helped in identification of two transcript variants; one transcript of 565 nucleotides and another alternate transcript of 207 nucleotides, seems to have arisen through alternative splicing. Both the transcripts were found to be expressed in most of the vital tissues of buffalo with the highest expression in mammary gland. Semi-quantitative and real-time expression analysis across 13 different buffalo tissues revealed its highest expression in lactating mammary gland. When compared, expression of FASN was also found to be higher in liver, adipose and skeletal muscle of buffalo tissues, than cattle. However, the FASN expression was highest in adipose among the three tissues in both the species. Results indicate structural and functional distinctiveness of bovine FASN. Presence of alternate splicing in buffalo FASN also seems to be a unique phenomenon to the bovines, probably associated with mRNA based regulation of the biological functions of FASN in these species. PMID- 26376070 TI - Martin Black award for the best paper published in 2014. PMID- 26376071 TI - An efficient transcriptome analysis pipeline to accelerate venom peptide discovery and characterisation. AB - Transcriptome sequencing is now widely adopted as an efficient means to study the chemical diversity of venoms. To improve the efficiency of analysis of these large datasets, we have optimised an analysis pipeline for cone snail venom gland transcriptomes. The pipeline combines ConoSorter with sequence architecture-based elimination and similarity searching using BLAST to improve the accuracy of sequence identification and classification, while reducing requirements for manual intervention. As a proof-of-concept, we used this approach reanalysed three previously published cone snail transcriptomes from diverse dietary groups. Our pipeline method generated similar results to the published studies with significantly less manual intervention. We additionally found undiscovered sequences in the piscovorous Conus geographus and vermivorous Conus miles and identified sequences in incorrect superfamilies in the molluscivorus Conus marmoreus and C. geographus transcriptomes. Our results indicate that this method can improve toxin detection without extending analysis time. While this method was evaluated on cone snail transcriptomes it can be easily optimised to retrieve toxins from other venomous animals. PMID- 26376072 TI - Rare Mullerian Anomaly: Complete Septate Uterus with Simultaneous Longitudinal and Transverse Vaginal Septa. AB - BACKGROUND: We present a patient with primary amenorrhea and a rare combination of anomalies. She was found to have a septate uterus, double cervix, and a longitudinal and a low transverse vaginal septum. CASE: An 18-year-old girl with primary amenorrhea presented with severe monthly pelvic pain. Examination and imaging revealed a thin transverse vaginal septum, complete septate uterus, double cervix, and a longitudinal vaginal septum. The transverse and longitudinal vaginal septa were excised and repaired. SUMMARY AND CONCLUSION: Although repetitive pregnancy loss and preterm birth are associated with various Mullerian duct anomalies, clinicians should also be suspicious of the presented anomaly in cases of primary amenorrhea and cyclic pelvic pain. To our knowledge, this is the only case of simultaneous septate uterus with longitudinal and transverse vaginal septum and the second case of combined longitudinal and transverse septum, which caused primary amenorrhea. This rare anomaly further supports the bidirectional regression theory of Mullerian development. PMID- 26376073 TI - Perinatal exposure to benzyl butyl phthalate induces alterations in neuronal development/maturation protein expression, estrogen responses, and fear conditioning in rodents. AB - Phthalate exposure has recently been associated with behavioral actions that are linked to its endocrine-disrupting properties. The purpose of this study was to investigate the molecular, anatomical, and behavioral effects of indirect perinatal benzyl butyl phthalate (BBP) exposure in offspring of BBP-treated pregnant dams. In two separate experiments, we administered BBP (10.0 MUg/ml) on food pellets to pregnant dams and examined the offspring. The first experiment revealed reproductive anatomical abnormalities linked to BBP's endocrine disrupting properties, whereas histological analysis revealed preserved hippocampal neuronal migration. The second experiment demonstrated learning and memory impairments accompanied by molecular abnormalities in multiple brain regions. Offspring from BBP-treated dams had altered levels of several proteins important for neuronal circuitry formation, tissue development, and maturation. We suggest that BBP administration disrupts normal learning and that these effects could be related to alterations in brain development and result in a phenotype similar to that observed in neurodevelopmental disorders. PMID- 26376074 TI - Neurodevelopmental Outcomes of Extremely Preterm Infants Randomized to Stress Dose Hydrocortisone. AB - OBJECTIVE: To compare the effects of stress dose hydrocortisone therapy with placebo on survival without neurodevelopmental impairments in high-risk preterm infants. STUDY DESIGN: We recruited 64 extremely low birth weight (birth weight <=1000 g) infants between the ages of 10 and 21 postnatal days who were ventilator-dependent and at high-risk for bronchopulmonary dysplasia. Infants were randomized to a tapering 7-day course of stress dose hydrocortisone or saline placebo. The primary outcome at follow-up was a composite of death, cognitive or language delay, cerebral palsy, severe hearing loss, or bilateral blindness at a corrected age of 18-22 months. Secondary outcomes included continued use of respiratory therapies and somatic growth. RESULTS: Fifty-seven infants had adequate data for the primary outcome. Of the 28 infants randomized to hydrocortisone, 19 (68%) died or survived with impairment compared with 22 of the 29 infants (76%) assigned to placebo (relative risk: 0.83; 95% CI, 0.61 to 1.14). The rates of death for those in the hydrocortisone and placebo groups were 31% and 41%, respectively (P = 0.42). Randomization to hydrocortisone also did not significantly affect the frequency of supplemental oxygen use, positive airway pressure support, or need for respiratory medications. CONCLUSIONS: In high-risk extremely low birth weight infants, stress dose hydrocortisone therapy after 10 days of age had no statistically significant effect on the incidence of death or neurodevelopmental impairment at 18-22 months. These results may inform the design and conduct of future clinical trials. TRIAL REGISTRATION: ClinicalTrials.gov NCT00167544. PMID- 26376076 TI - Improved Carbohydrate Recognition in Water with an Electrostatically Enhanced beta-Peptide Bundle. AB - The selective recruitment of oligosaccharides, or even simple sugars, in water solvent is an unsolved molecular recognition problem. Structure-guided, electrostatic redesign led to a significant increase in the affinity of a beta peptide "borono-bundle" for simple sugars in neutral aqueous solution. The affinity for fructose (663 M(-1)) in water should allow its recruitment to the bundle surface for selective catalysis, and future work will focus in this direction. PMID- 26376075 TI - Serum Gamma-Glutamyltransferase Levels Predict Clinical Outcomes in Hemodialysis Patients. AB - BACKGROUND: Gamma-glutamyltransferase (GGT) is a biomarker of liver injury. GGT has also been reported to be a marker of oxidative stress and a predictor of mortality in the general population. Hemodialysis (HD) patients suffer from oxidative stress. The aim of our study was to investigate the relationship between serum GGT levels and clinical outcomes in HD patients. METHODS: A total of 1,634 HD patients were enrolled from the Clinical Research Center registry for end-stage renal disease, a prospective cohort in Korea. Patients were categorized into three groups by tertiles of serum GGT levels. The primary outcome was all cause, cardiovascular, or infection-related mortality and hospitalization. RESULTS: During the median follow-up period of 30 months, the highest tertile of serum GGT levels had a significantly higher risk for all-cause mortality (hazard ratio (HR) 2.39, 95% confidence interval (CI), 1.55-3.69, P<0.001), cardiovascular mortality (HR 2.14, 95% CI, 1.07-4.26, P = 0.031) and infection related mortality (HR 3.07, 95% CI, 1.30-7.25, P = 0.011) using tertile 1 as the reference group after adjusting for clinical variables including liver diseases. The highest tertile also had a significantly higher risk for first hospitalization (HR 1.22, 95% CI, 1.00-1.48, P = 0.048) and cardiovascular hospitalization (HR 1.42, 95% CI, 1.06-1.92, P = 0.028). CONCLUSIONS: Our data demonstrate that high serum GGT levels were an independent risk factor for all cause, cardiovascular, and infection-related mortality, as well as cardiovascular hospitalization in HD patients. These findings suggest that serum GGT levels might be a useful biomarker to predict clinical outcomes in HD patients. PMID- 26376077 TI - Prospective Cohort Study of Central Adiposity and Risk of Death in Middle Aged and Elderly Chinese. AB - Asians have high prevalence of central obesity despite the low prevalence of general obesity. We evaluated associations between the central obesity measure, waist-hip ratio (WHR) with total and cause-specific mortality in middle-aged and elderly Chinese participants. Data arise from two prospective population-based cohort studies: the Shanghai Men's Health Study involves 53,425 men (participation rate = 74.0%), age 40-74 at baseline, and the Shanghai Women's Health Study involves 63,017 women (participation rate = 92.7%), age 40-70 at baseline. Information on lifestyle factors and anthropometric measurements were taken at baseline interview. Vital status and causes of death were obtained via surveys and annual linkages to relevant Shanghai registries through December 31, 2011. After median follow-up time of 7.5 years for the Shanghai Men's Health Study and 13.2 years for the Shanghai Women's Health Study, there were 2,058 and 3,167 deaths, respectively. In models adjusted for BMI and other potential confounders, WHR was associated with all-cause mortality; hazard ratios (HRs) (95% confidence intervals) across the first to fifth quintile increased from 1 (Reference), 1.10 (0.95,1.27), 1.21 (1.04,1.41), 1.11 (0.96,1.30), to 1.42 (1.22,1.65) in men and from 1 (Reference), 1.10 (0.96,1.27), 1.11 (0.97,1.27), 1.20 (1.05,1.37), to 1.48 (1.30,1.69) in women. WHR had a stronger association with cardiovascular disease, with multivariate-adjusted HRs of 1.5 to 1.7 observed for the highest versus lowest quintile of WHR. Dose-response associations were also seen for cancer and other-cause deaths. Stratified analyses suggested a stronger association with mortality among normal weight (BMI <25) than over-weight (BMI >=25) individuals. Positive associations with mortality were observed in subgroups defined by follow-up duration, comorbidity, age, smoking, and physical activity. Greater central adiposity is associated with increased mortality in Chinese adults, even among individuals with low BMI. Physicians and the public should be aware of central adiposity's independent effects on health. PMID- 26376079 TI - Correction: Cancer Incidence following Expansion of HIV Treatment in Botswana. PMID- 26376078 TI - Attention Deficit Hyperactivity Disorder Symptoms, Sleepiness and Accidental Risk in 36140 Regularly Registered Highway Drivers. AB - BACKGROUND: Attention Deficit Hyperactivity Disorder (ADHD) is a frequent neurodevelopmental disorder that increases accidental risk. Recent studies show that some patients with ADHD can also suffer from excessive daytime sleepiness but there are no data assessing the role of sleepiness in road safety in patients with ADHD. We conducted an epidemiological study to explore sleep complaints, inattention and driving risks among automobile drivers. METHODS AND FINDINGS: From August to September 2014, 491186 regular highway users were invited to participate in an Internet survey on driving habits. 36140 drivers answered a questionnaire exploring driving risks, sleep complaints, sleepiness at the wheel, ADHD symptoms (Adult ADHD Self-Report Scale) and distraction at the wheel. 1.7% of all drivers reported inattention-related driving accidents and 0.3% sleep related driving accidents in the previous year. 1543 drivers (4.3%) reported ADHD symptoms and were more likely to report accidents than drivers without ADHD symptoms (adjusted OR = 1.24, [1.03-1.51], p < .021). 14.2% of drivers with ADHD symptoms reported severe excessive daytime sleepiness (Epworth Sleepiness Scale >15) versus 3.2% of drivers without ADHD symptoms and 20.5% reported severe sleepiness at the wheel versus 7.3%. Drivers with ADHD symptoms reported significantly more sleep-related (adjusted OR = 1.4, [1.21-1.60], p < .0001) and inattention-related (adjusted OR = 1.9, [1.71-2.14], p<0001) near misses than drivers without ADHD symptoms. The fraction of near-misses attributable to severe sleepiness at the wheel was 4.24% for drivers without ADHD symptoms versus 10,35% for drivers with ADHD symptoms. CONCLUSION: Our study shows that drivers with ADHD symptoms have more accidents and a higher level of sleepiness at the wheel than drivers without ADHD symptoms. Drivers with ADHD symptoms report more sleep related and inattention-related near misses, thus confirming the clinical importance of exploring both attentional deficits and sleepiness at the wheel in these drivers. Road safety campaigns should be improved to better inform drivers of these accidental risks. PMID- 26376080 TI - Role of pharmacotherapy in cardiac ion channelopathies. AB - In the last decade, there have been considerable advances in the understanding of the pathophysiology of malignant ventricular tachyarrhythmias (VT) and sudden cardiac death (SCD). Over 80% of SCD occurs in patients with organic heart disease. However, approximately 10%-15% of SCD occurs in the presence of structurally normal heart, and the majority of these patients are young. In this group of patients, changes in genes encoding cardiac ion channels produce modifications of the function of the channel resulting in an electrophysiological substrate of VT and SCD. Collectively, these disorders are referred to as cardiac ion channelopathies. The four major syndromes in this group are: the long QT syndrome (LQTS), the Brugada syndrome (BrS), the short QT syndrome (SQTS), and the catecholaminergic polymorphic ventricular tachycardia (CPVT). Each of these syndromes includes multiple subtypes with different and sometimes complex cardiac ion channel genetic abnormalities. Many are associated with other somatic and neurological abnormalities besides the risk of VT and SCD. The current management of cardiac ion channelopathies can be summarized as follows: (1) in symptomatic patients, the implantable cardioverter defibrillator (ICD) is the only viable option; (2) in asymptomatic patients, risk stratification is necessary, followed by either the ICD, pharmacotherapy, or a combination of both. A genotype-specific approach to pharmacotherapy requires a thorough understanding of the molecular cellular basis of arrhythmogenesis in cardiac ion channelopathies as well as the specific drug profile. PMID- 26376081 TI - Sleep deprivation and anxiety in humans and rodents--translational considerations and hypotheses. AB - The effects of acute sleep deprivation on anxiety are the focus of controversy in the literature. While clinical research studies on the effects of sleep deprivation seem to show a consistent increase in acute anxiety, rodent studies have produced inconsistent results, with some experiments pointing to anxiogenesis and others to anxiolysis. Such observations impair the translational applicability of rodent models on the paradigm between sleep deprivation and anxiety. Current studies fail in the very basic principle of biomedical translational research: to provide relevant and reliable knowledge from basic experimental science that can be applied in clinical environments. Possible explanations for the disparity between human and animal studies include the accuracy of both human and rodent research, the ability of current behavioral protocols to truly reflect the anxiety response of rodents to sleep deprivation, and the nature of sleep deprivation-induced anxiety in rodents. Based on these hypotheses, we performed a brief overview of the literature on the relationship between sleep deprivation and anxiety and propose a research agenda that could lead to a better understanding of the reasons for the discrepancies found in the literature and provide more reliable data on the translational relationship between sleep deprivation and anxiety. PMID- 26376082 TI - Reduced Inhibition of Return to Food Images in Obese Individuals. AB - Previous research has shown that obese individuals may be biased towards attending to food over non-food information, and this bias may contribute to the development and/or maintenance of obesity. The present study sought to extend our understanding of maladaptive attentional processing in this population by investigating whether obese individuals have difficulty in disengaging attention from food compared with non-food images, relative to normal-weight controls. To address this question, we measured inhibition of return (IOR) in an attentional cueing task. The participants were 29 obese and 35 normal-weight satiated females without eating disorders. The obese group displayed less IOR to food images than the normal-weight group, while there was no difference in IOR between the groups for non-food images. This suggests that obese females have greater difficulty disengaging attention from food than normal-weight females. Our findings provide a new focus for studies investigating maintenance factors in obesity and are discussed in relation to a theory of incentive-sensitisation. PMID- 26376084 TI - Safety and Short-term Outcomes of a Single-Port Laparoscopic Approach to Colorectal Surgery. PMID- 26376083 TI - Acrylamide and glycidamide hemoglobin adduct levels and endometrial cancer risk: A nested case-control study in nonsmoking postmenopausal women from the EPIC cohort. AB - Acrylamide, classified in 1994 by IARC as "probably carcinogenic to humans," was discovered in 2002 in some heat-treated, carbohydrate-rich foods. Four prospective studies have evaluated the association between dietary acrylamide intake and endometrial cancer (EC) risk with inconsistent results. The purpose of this nested case-control study, based on the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, was to evaluate, for the first time, the association between hemoglobin adducts of acrylamide (HbAA) and glycidamide (HbGA) and the risk of developing EC in non-smoking postmenopausal women. Hemoglobin adducts were measured in red blood cells by HPLC/MS/MS. Four exposure variables were evaluated: HbAA, HbGA, their sum (HbAA+HbGA), and their ratio (HbGA/HbAA). The association between hemoglobin adducts and EC was evaluated using unconditional multivariable logistic regression models, and included 383 EC cases (171 were type-I EC), and 385 controls. Exposure variables were analyzed in quintiles based on control distributions. None of the biomarker variables had an effect on overall EC (HRHbAA;Q5vsQ1 : 0.84, 95%CI: 0.49-1.48; HRHbGA;Q5vsQ1 : 0.94, 95%CI: 0.54-1.63) or type-I EC risk. Additionally, none of the subgroups investigated (BMI < 25 vs. >=25 kg m(-2) , alcohol drinkers vs. never drinkers, oral contraceptive users vs. non-users) demonstrated effect measure modification. Hemoglobin adducts of acrylamide or glycidamide were not associated with EC or type-I EC risk in 768 nonsmoking postmenopausal women from the EPIC cohort. PMID- 26376085 TI - Tuberculosis and latent tuberculosis infection among healthcare workers in Kisumu, Kenya. AB - OBJECTIVE: To assess prevalence and occupational risk factors of latent TB infection and history of TB disease ascribed to work in a healthcare setting in western Kenya. METHODS: We conducted a cross-sectional survey among healthcare workers in western Kenya in 2013. They were recruited from dispensaries, health centres and hospitals that offer both TB and HIV services. School workers from the health facilities' catchment communities were randomly selected to serve as the community comparison group. Latent TB infection was diagnosed by tuberculin skin testing. HIV status of participants was assessed. Using a logistic regression model, we determined the adjusted odds of latent TB infection among healthcare workers compared to school workers; and among healthcare workers only, we assessed work-related risk factors for latent TB infection. RESULTS: We enrolled 1005 healthcare workers and 411 school workers. Approximately 60% of both groups were female. A total of 22% of 958 healthcare workers and 12% of 392 school workers tested HIV positive. Prevalence of self-reported history of TB disease was 7.4% among healthcare workers and 3.6% among school workers. Prevalence of latent TB infection was 60% among healthcare workers and 48% among school workers. Adjusted odds of latent TB infection were 1.5 times higher among healthcare workers than school workers (95% confidence interval 1.2-2.0). Healthcare workers at all three facility types had similar prevalence of latent TB infection (P = 0.72), but increasing years of employment was associated with increased odds of LTBI (P < 0.01). CONCLUSION: Healthcare workers at facilities in western Kenya which offer TB and HIV services are at increased risk of latent TB infection, and the risk is similar across facility types. Implementation of WHO-recommended TB infection control measures are urgently needed in health facilities to protect healthcare workers. PMID- 26376086 TI - Clinical Research Abstracts of the British Equine Veterinary Association Congress 2015. AB - REASONS FOR PERFORMING STUDY: Injury to the superficial digital flexor tendon (SDFT) is common in equids, with a high risk of re-injury associated with changes in tendon stiffness. In vivo measurement of limb stiffness has been shown to correlate with tendon stiffness after injury [1] but requires kinematic analysis which is impractical in a clinical setting. We have developed a simple system for measuring limb stiffness statically, which could be used as a tool for monitoring SDFT healing. OBJECTIVES: To validate a goniometric measurement of limb stiffness. STUDY DESIGN: Cross sectional study. METHODS: Initially, forelimb stiffness indices were determined at the walk for 6 equids using a validated kinematic analysis [1]. Limb stiffness indices were then calculated using portable floor scales to record ground reaction force (GRF), and an electrogoniometer to record metacarpophalangeal joint angle. Goniometric limb stiffness indices were subsequently measured in 11 horses ranging from 2 to 20 years of age, with no clinical evidence of SDFT injury. Strength and significance of correlation and agreement between the measurement methods was assessed and association between limb stiffness, limb (left vs. right), weight and age of horse and were calculated. RESULTS: There were strong positive correlations between GRF and joint angle (R(2) = 0.98) and between the static and kinematic methods (R = 0.78, P<0.01). There was a positive correlation between limb stiffness and weight (R(2) = 0.85, P<0.01), but no association with age or limb. CONCLUSIONS: This study validated the measurement of limb stiffness in a clinical setting. The positive correlation of limb stiffness and weight supports the theory of an optimised limb spring [2] for energy-efficient cursorial locomotion which may, in turn, provide a clinically-relevant measure of running efficiency and therefore the quality of tendon healing post injury. Ethical animal research: Owner consent was obtained. SOURCE OF FUNDING: None. Competing interests: None declared. PMID- 26376087 TI - High Performance Ultrathin GaAs Solar Cells Enabled with Heterogeneously Integrated Dielectric Periodic Nanostructures. AB - Due to their favorable materials properties including direct bandgap and high electron mobilities, epitaxially grown III-V compound semiconductors such as gallium arsenide (GaAs) provide unmatched performance over silicon in solar energy harvesting. Nonetheless, their large-scale deployment in terrestrial photovoltaics remains challenging mainly due to the high cost of growing device quality epitaxial materials. In this regard, reducing the thickness of constituent active materials under appropriate light management schemes is a conceptually viable option to lower the cost of GaAs solar cells. Here, we present a type of high efficiency, ultrathin GaAs solar cell that incorporates bifacial photon management enabled by techniques of transfer printing to maximize the absorption and photovoltaic performance without compromising the optimized electronic configuration of planar devices. Nanoimprint lithography and dry etching of titanium dioxide (TiO2) deposited directly on the window layer of GaAs solar cells formed hexagonal arrays of nanoscale posts that serve as lossless photonic nanostructures for antireflection, diffraction, and light trapping in conjunction with a co-integrated rear-surface reflector. Systematic studies on optical and electrical properties and photovoltaic performance in experiments, as well as numerical modeling, quantitatively describe the optimal design rules for ultrathin, nanostructured GaAs solar cells and their integrated modules. PMID- 26376088 TI - Multi-Target Analysis and Design of Mitochondrial Metabolism. AB - Analyzing and optimizing biological models is often identified as a research priority in biomedical engineering. An important feature of a model should be the ability to find the best condition in which an organism has to be grown in order to reach specific optimal output values chosen by the researcher. In this work, we take into account a mitochondrial model analyzed with flux-balance analysis. The optimal design and assessment of these models is achieved through single- and/or multi-objective optimization techniques driven by epsilon-dominance and identifiability analysis. Our optimization algorithm searches for the values of the flux rates that optimize multiple cellular functions simultaneously. The optimization of the fluxes of the metabolic network includes not only input fluxes, but also internal fluxes. A faster convergence process with robust candidate solutions is permitted by a relaxed Pareto dominance, regulating the granularity of the approximation of the desired Pareto front. We find that the maximum ATP production is linked to a total consumption of NADH, and reaching the maximum amount of NADH leads to an increasing request of NADH from the external environment. Furthermore, the identifiability analysis characterizes the type and the stage of three monogenic diseases. Finally, we propose a new methodology to extend any constraint-based model using protein abundances. PMID- 26376090 TI - Clinical Research Abstracts of the British Equine Veterinary Association Congress 2015. AB - REASONS FOR PERFORMING STUDY: Pleural effusion (PE) is reported to occur most commonly secondary to bacterial pneumonia or lung abscesses, with neoplastic effusions contributing the minority of cases. The majority of these reports originate from America and Australia, where long distance transport of horses, a recognised risk factor, appears to occur more frequently. Anecdotally, neoplastic PE is more commonly diagnosed in the UK. OBJECTIVES: To describe the causes of PE in horses resident in the UK, and to identify potential markers that can help differentiate between infectious and neoplastic causes of PE. STUDY DESIGN: Retrospective clinical study. METHODS: Medical records from 4 referral hospitals in southern England were searched for horses diagnosed with PE. Information gathered from medical records included signalment, diagnosis (infectious vs. neoplastic), admission physical examination and biochemical findings, and characteristics of the effusion (volume, cell count, total protein [TP] concentration). Statistical comparisons were made between the neoplastic and infectious group using appropriate testing. RESULTS: Seventy horses were identified, of which 28 (40%) were neoplastic and 42 were infectious. Horses with infectious effusions were significantly younger (median 7 vs. 13 years; P = 0.002) and had significantly smaller volumes of pleural fluid drained at admission (9.8 vs. 32.3 l; P<0.001). Horses with infectious PE had a significantly higher rectal temperature (38.6 vs. 38.2 degrees C; P = 0.03), fibrinogen concentration (7.8 vs. 5.7 g/l; P = 0.02) and serum amyloid A concentration (223 vs. 104 mg/l; P = 0.02). Pleural fluid characteristics identified a significantly greater cell count and TP concentration in horses with infectious PE (47 x 10(9)/l vs. 3.4 x 10(9)/l; P<0.001; 54 vs. 31 g/l; P = 0.001). CONCLUSIONS: These results suggest that in the UK neoplastic effusions account for a greater proportion of PE than previously reported. A large volume of PE in an older horse with a low cell count and TP concentration should increase the index of suspicion of neoplasia. Ethical animal research: This was a retrospective study of clinical cases. Explicit owner informed consent for inclusion of animals in this study was not stated. SOURCE OF FUNDING: None. Competing interests: None declared. PMID- 26376089 TI - Generalization of Dexterous Manipulation Is Sensitive to the Frame of Reference in Which It Is Learned. AB - Studies have shown that internal representations of manipulations of objects with asymmetric mass distributions that are generated within a specific orientation are not generalizable to novel orientations, i.e., subjects fail to prevent object roll on their first grasp-lift attempt of the object following 180 degrees object rotation. This suggests that representations of these manipulations are specific to the reference frame in which they are formed. However, it is unknown whether that reference frame is specific to the hand, the body, or both, because rotating the object 180 degrees modifies the relation between object and body as well as object and hand. An alternative, untested explanation for the above failure to generalize learned manipulations is that any rotation will disrupt grasp performance, regardless if the reference frame in which the manipulation was learned is maintained or modified. We examined the effect of rotations that (1) maintain and (2) modify relations between object and body, and object and hand, on the generalizability of learned two-digit manipulation of an object with an asymmetric mass distribution. Following rotations that maintained the relation between object and body and object and hand (e.g., rotating the object and subject 180 degrees ), subjects continued to use appropriate digit placement and load force distributions, thus generating sufficient compensatory moments to minimize object roll. In contrast, following rotations that modified the relation between (1) object and hand (e.g. rotating the hand around to the opposite object side), (2) object and body (e.g. rotating subject and hand 180 degrees ), or (3) both (e.g. rotating the subject 180 degrees ), subjects used the same, yet inappropriate digit placement and load force distribution, as those used prior to the rotation. Consequently, the compensatory moments were insufficient to prevent large object rolls. These findings suggest that representations of learned manipulation of objects with asymmetric mass distributions are specific to the body- and hand-reference frames in which they were learned. PMID- 26376091 TI - Construction of Oxadiazepines via Lewis Acid-Catalyzed Tandem 1,5-Hydride Shift/Cyclization. AB - Expeditious access to oxadiazepines via 1,5-hydride shift/cyclization of pyrrolidine- or tetrahydroisoquinoline-containing nitrones has been developed. With 1,3-dipole nitrones serving as the hydride acceptors, this transformation was promoted by a Lewis acid, providing access to structurally diverse oxadiazepines in good yields. A one-pot process for in situ nitrone formation, a 1,5-hydride shift, and ring cyclization was also realized. PMID- 26376092 TI - Moraxella osloensis, an emerging pathogen of endocarditis in immunocompromised patients? AB - We report two cases of endocarditis due to Moraxella osloensis. Only one previous case of such infection has been described. These infections occurred in immunocompromised patients (B-cell chronic lymphocytic leukaemia and kidney graft associated with Hodgkin's disease) and both patients had a favourable outcome with a complete cure of their infectious endocarditis. This bacterium could be an emerging pathogen revealed by MALDI-TOF. Indeed, its characterisation within the Moraxella group by use of biochemistry-based methods is difficult. Moreover, this strain could be particularly involved in immunocompromised patients. PMID- 26376094 TI - Mask-Free Patterning of High-Conductivity Metal Nanowires in Open Air by Spatially Modulated Femtosecond Laser Pulses. AB - A novel high-resolution nanowire fabrication method is developed by thin-film patterning using a spatially modulated femtosecond laser pulse. Deep subwavelength (~1/13 of the laser wavelength) and high conductivity (~1/4 of the bulk gold) nanowires are fabricated in the open air without using masks, which offers a single-step arbitrary direct patterning approach for electronics, plasmonics, and optoelectronics nanodevices. PMID- 26376093 TI - Multilevel Approach of a 1-Year Program of Dietary and Exercise Interventions on Bone Mineral Content and Density in Metabolic Syndrome--the RESOLVE Randomized Controlled Trial. AB - BACKGROUND: Weight loss is a public health concern in obesity-related diseases such as metabolic syndrome (MetS). However, restrictive diets might induce bone loss. The nature of exercise and whether exercise with weight loss programs can protect against potential bone mass deficits remains unclear. Moreover, compliance is essential in intervention programs. Thus, we aimed to investigate the effects that modality and exercise compliance have on bone mineral content (BMC) and density (BMD). METHODS: We investigated 90 individuals with MetS who were recruited for the 1-year RESOLVE trial. Community-dwelling seniors with MetS were randomly assigned into three different modalities of exercise (intensive resistance, intensive endurance, moderate mixed) combined with a restrictive diet. They were compared to 44 healthy controls who did not undergo the intervention. RESULTS: This intensive lifestyle intervention (15-20 hours of training/week + restrictive diet) resulted in weight loss, body composition changes and health improvements. Baseline BMC and BMD for total body, lumbar spine and femoral neck did not differ between MetS groups and between MetS and controls. Despite changes over time, BMC or BMD did not differ between the three modalities of exercise and when compared with the controls. However, independent of exercise modality, compliant participants increased their BMC and BMD compared with their less compliant peers. Decreases in total body lean mass and negative energy balance significantly and independently contributed to decreases in lumbar spine BMC. CONCLUSION: After the one year intervention, differences relating to exercise modalities were not evident. However, compliance with an intensive exercise program resulted in a significantly higher bone mass during energy restriction than non-compliance. Exercise is therefore beneficial to bone in the context of a weight loss program. TRIAL REGISTRATION: ClinicalTrials.gov NCT00917917. PMID- 26376095 TI - Clinical Research Abstracts of the British Equine Veterinary Association Congress 2015. AB - REASONS FOR PERFORMING STUDY: Selective 5-HT4 receptor agonists such as prucalopride are used as human prokinetics, since activation of 5-HT4 receptors on intestinal cholinergic neurons facilitates acetylcholine release. 5-HT4 receptors, linked to adenylyl cyclase, act via generation of cAMP. None of the 4 in vitro studies on 5-HT in horses provided evidence for neuronal 5-HT4 receptors, but none used the protocol as described in human studies [1-4]. OBJECTIVES: To investigate whether functional 5-HT4 receptors are present in the equine small intestine. STUDY DESIGN AND METHODS: In vitro organ bath set up, applying electrical field stimulation (EFS) in longitudinal and circular smooth muscle strips. RESULTS: Results were similar in both muscle layers. In the presence of 0.3 mmol/l NG-Nitro-L-arginine methyl ester and 0.3 MUmol/l apamine, excluding effects of the inhibitory transmitters NO and ATP, EFS induced voltage dependent on-contractions; these were neurogenic as they were abolished by 3 MUmol/l tetrodotoxin. At a voltage inducing 50% of the maximal amplitude, the submaximal EFS-induced contractions were cholinergic as atropine (1 MUmol/l) abolished them. Prucalopride (0.3 MUmol/l) did not increase the amplitude of these submaximal EFS-induced contractions. Even in the presence of the nonselective phosphodiesterase inhibitor IBMX, previously shown to enhance the effect of neuronal 5-HT4 receptors by inhibiting breakdown of their 2nd messenger cAMP [5], prucalopride (3 MUmol/l) had no influence. Also 5-HT (10 MUmol/l), a full agonist at 5-HT4 receptors, tested in the presence of methysergide and granisetron to exclude interaction with other 5-HT receptor subtypes, did not enhance EFS-induced submaximal contractions. CONCLUSIONS: There is no evidence for presence of 5-HT4 receptors on the cholinergic neurons of the equine small intestine. These results question the application of 5-HT4 prokinetic drugs in horses. Ethical animal research: Research ethics committee oversight not currently required by this conference: the study was performed on material collected at an abattoir. Sources of funding: None. Competing interests: None declared. PMID- 26376096 TI - Differential proteomics reveals age-dependent liver oxidative costs of innate immune activation in mice. AB - Individual response to an immune challenge results from the optimization of a trade-off between benefits and costs of immune cell activation. Age-related immune disorders may have several mechanistic bases, from immune cell defects to chronic pro-inflammatory status and oxidative imbalance, but we are still lacking experimental data showing the relative importance of each of these mechanisms. Using a proteomic approach and subsequent biochemical validations of proteomics derived hypotheses, we found age-dependent regulations in the liver of 3-months and 1-year old-mice in response to an acute innate immune activation. Old mice presented a chronic up-regulation of several proteins involved in pathways related to oxidative stress control. Interestingly, these pathways were weakly affected by the innate immune activation in old compared to young individuals. In addition, old mice suffered from lower glutathione-S-transferase activity and from higher oxidative damage at the end of the experiment, thus suggesting that they paid a higher immune-related cost than young individuals. On the whole, our data showed that a substantial fraction of the liver costs elicited by an activation of the innate immune response is effectively related to oxidative stress, and that ageing impairs the capacity of old individuals to control it. SIGNIFICANCE: Our paper tackles the open question of the cost of mounting an innate immune response. Evolutionary biologists are familiar since a long time with the concept of trade-offs among key traits of an organism, trade-offs that shape life history trajectories of species and individuals, ultimately in terms of reproduction and survival. On the other hand, medicine and molecular biologists study the intimate mechanisms of immune senescence and underline that oxidative imbalance is probably playing a key role in the progressive loss of immune function with age. This paper merges the two fields by exploring the nature of the cellular pathways that are mainly affected by age when the innate immunity is triggered. To this purpose, a proteomic approach was used to explore liver protein profiles and provide for the first time convincing data supporting the idea that oxidative stress constitutes a cost of innate immune response in old mice, possibly contributing to senescence. Proteomics-derived hypotheses were furthermore validated using biochemical assays. This paper therefore illustrates the added value of using proteomics to answer evolutionary biology questions, and opens a promising way to study the inter-specific variability in the rates of immune-senescence. PMID- 26376097 TI - Proteomic and bioinformatic analysis of a nuclear intrinsically disordered proteome. AB - Intrinsically disordered proteins (IDPs) are biologically active and crucial for cell function although they do not possess defined three-dimensional architecture. IDPs are especially prevalent in eukaryotic proteomes, and large scale experiments have shown that many IDPs are nuclear proteins. Bioinformatic analyses have also demonstrated that the vast majority of transcription factors contain extended regions of intrinsic disorder. In the current study, we isolated and functionally analyzed IDPs expressed in the nuclei of HEK293 human cells. According to the results of MS analysis followed by subsequent analysis with the bioinformatic tools IUPred and RAPID (regression-based accurate predictor of intrinsic disorder), a heat-treatment method was able to enrich the nuclear lysate in IDPs. For approximately 85% of the proteins obtained, IUPred predicted a sequence of 30 or more consecutive disordered residues (DRs), and for approximately 83% of the proteins RAPID reported a content of at least 25% DRs (compared to ~66% and 49%, respectively, for the nuclear lysate). Gene Ontology analysis in terms of molecular function revealed that the obtained fraction was generally enriched in proteins involved in the process of transcription and especially in transcription factors. We also showed experimentally that IDPs are overrepresented in the cell nucleus. SIGNIFICANCE: Intrinsically disordered proteins (IDPs) are crucial cellular molecules and are especially numerous in eukaryotes. In particular, IDPs act as signaling and regulatory proteins, and impairment in their functioning may lead to serious diseases. Large-scale bioinformatic studies of IDPs have provided essential knowledge about this group of proteins. However, experimental data reflect the actual situation in living cells. Our study is the first large-scale proteomic analysis of nuclear IDPs. We showed experimentally that IDPs are overrepresented in the nucleus in comparison to the whole cell. Analysis of molecular function indicated that the nuclear intrinsically disordered proteome (IDP-ome) is enriched in proteins involved in transcription regulation and especially in transcription factors. The IDP isolation method from human cell nuclei presented in this article could be further applied in differential proteomic studies. PMID- 26376098 TI - Secreted protein eco-corona mediates uptake and impacts of polystyrene nanoparticles on Daphnia magna. AB - Nanoparticles (NPs) are defined as having at least one external dimension between 1 and 100 nm. Due to their small size, NPs have a large surface area to volume ratio giving them unique characteristics that differ from bulk material of the same chemical composition. As a result these novel materials have found numerous applications in medical and industrial fields with the result that environmental exposure to NPs is increasingly likely. Similarly, increased reliance on plastic, which degrades extremely slowly in the environment, is resulting in increased accumulation of micro-/nano-plastics in fresh and marine waters, whose ecotoxicological impacts are as yet poorly understood. Although NPs are well known to adsorb macromolecules from their environment, forming a biomolecule corona which changes the NP identity and how it interacts with organisms, significantly less research has been performed on the ecological corona (eco corona). Secretion of biomolecules is a well established predator-prey response in aquatic food chains, raising the question of whether NPs interact with secreted proteins, and the impact of such interaction on NP uptake and ecotoxicity. We report here initial studies, including optimisation of protocols using carboxylic-acid and amino modified spherical polystyrene NPs, to assess interaction of NPs with biomolecules secreted by Daphnia magna and the impact of these interactions on NP uptake, retention and toxicity towards Daphnia magna. BIOLOGICAL SIGNIFICANCE: Daphnia magna are an important environmental indicator species who may be especially sensitive to nanoparticles (NPs) as a result of being filter-feeders. This paper demonstrates for the first time that proteins released by Daphnia magna create an eco-corona around polystyrene NPs which causes heightened uptake of the NPs and consequently increases toxicity. The secreted protein eco-corona also causes the NPs to be less efficiently removed from the gut of D. magna and NPs remaining in the gut of D. magna affected the rate of subsequent feeding. Thus, fate of NPs in the environment should be evaluated and monitored under more realistic exposure scenarios. PMID- 26376099 TI - Gel-free/label-free proteomic analysis of root tip of soybean over time under flooding and drought stresses. AB - Growth in the early stage of soybean is markedly inhibited under flooding and drought stresses. To explore the responsive mechanisms of soybean, temporal protein profiles of root tip under flooding and drought stresses were analyzed using gel-free/label-free proteomic technique. Root tip was analyzed because it was the most sensitive organ against flooding, and it was beneficial to root penetration under drought. UDP glucose: glycoprotein glucosyltransferase was decreased and increased in soybean root under flooding and drought, respectively. Temporal protein profiles indicated that fermentation and protein synthesis/degradation were essential in root tip under flooding and drought, respectively. In silico protein-protein interaction analysis revealed that the inductive and suppressive interactions between S-adenosylmethionine synthetase family protein and B-S glucosidase 44 under flooding and drought, respectively, which are related to carbohydrate metabolism. Furthermore, biotin/lipoyl attachment domain containing protein and Class II aminoacyl tRNA/biotin synthetases superfamily protein were repressed in the root tip during time-course stresses. These results suggest that biotin and biotinylation might be involved in energy management to cope with flooding and drought in early stage of soybean root tip. PMID- 26376100 TI - Clinical Evaluation and Patient Satisfaction of Single Zirconia-Based and High Noble Alloy Porcelain-Fused-to-Metal Crowns in the Esthetic Area: A Retrospective Cohort Study. AB - PURPOSE: The aim of this study was to assess clinical survival, complications, and patient satisfaction with single zirconia-based crowns (ZC) or high-noble alloy PFM crowns (HC) in esthetic areas. MATERIALS AND METHODS: The study was a retrospective cohort study with up to 3.8 years follow-up (mean 2.5 years). Patients who met the inclusion criteria were reviewed. Survival rates, complications, satisfaction rates (color and form), and overall satisfaction (visual analogue scale, VAS) were evaluated by follow-up examination. Chi-square test (survival, complication, and satisfaction rate) and unpaired t-test (overall satisfaction: VAS) were used to test the difference between the ZC and HC groups. Survival rates and complications were assessed both at subject-level (patient as statistical unit) and at tooth-level (tooth as statistical unit). RESULTS: One hundred and thirteen patients met the inclusion criteria; 95 patients (ZC: 45, HC: 50) with 132 crowns (ZC: 61, HC: 71) were enrolled in the study. The overall survival rate was 93.3% for ZC crowns and 96.0% for HC crowns at subject-level and 93.4% for ZC crowns and 97.2% for HC crowns at tooth-level (p = 0.56 and 0.30, respectively). Veneer chipping was the most frequently seen complication. One HC crown lost retention because of poor cementation. One patient in the ZC group showed progression of periodontal disease. No significant difference of complications was found between the two groups at subject-level and tooth-level (p = 0.37 and 0.34, respectively). The overall satisfaction (VAS) was 8.18 for ZC crowns and 8.46 for HC crowns (p = 0.34). CONCLUSIONS: The results of the study showed that a high survival rate could be achieved in both ZC and HC groups. Chipping of the veneering porcelain was the most frequently seen event that led to short-term (less than 3 years) failure and complications. The patients' rating of ZC crowns was not superior to HC crowns. Well-designed studies with high evidence level and large sample size are still needed to further explore the clinical success of ZC and HC crowns. PMID- 26376101 TI - The development of SERI(r) Surgical Scaffold, an engineered biological scaffold. AB - The primary goal of reconstructive and revision surgery is to restore, repair, rebuild, and support damaged, weakened, or absent tissue. There are numerous approaches for soft tissue support and repair, including the use of autologous tissue, human- or animal-derived acellular dermal matrices, absorbable or permanent synthetic mesh, and, now, a new class of bioresorbable protein scaffold. Although many factors influence the choice of surgical approach and the specific product used for soft tissue support and repair, the goal is to improve long-term outcomes while minimizing complications and recurrences requiring further revisional surgery. In this review, the basic science, clinical characteristics, and clinical applications of SERI((r)) Surgical Scaffold, a novel, engineered, highly purified silk product for soft tissue support and repair will be presented. PMID- 26376102 TI - Endogenous recovery after brain damage: molecular mechanisms that balance neuronal life/death fate. AB - Neuronal survival depends on multiple factors that comprise a well-fueled energy metabolism, trophic input, clearance of toxic substances, appropriate redox environment, integrity of blood-brain barrier, suppression of programmed cell death pathways and cell cycle arrest. Disturbances of brain homeostasis lead to acute or chronic alterations that might ultimately cause neuronal death with consequent impairment of neurological function. Although we understand most of these processes well when they occur independently from one another, we still lack a clear grasp of the concerted cellular and molecular mechanisms activated upon neuronal damage that intervene in protecting damaged neurons from death. In this review, we summarize a handful of endogenously activated mechanisms that balance molecular cues so as to determine whether neurons recover from injury or die. We center our discussion on mechanisms that have been identified to participate in stroke, although we consider different scenarios of chronic neurodegeneration as well. We discuss two central processes that are involved in endogenous repair and that, when not regulated, could lead to tissue damage, namely, trophic support and neuroinflammation. We emphasize the need to construct integrated models of neuronal degeneration and survival that, in the end, converge in neuronal fate after injury. Under neurodegenerative conditions, endogenously activated mechanisms balance out molecular cues that determine whether neurons contend toxicity or die. Many processes involved in endogenous repair may as well lead to tissue damage depending on the strength of stimuli. Signaling mediated by trophic factors and neuroinflammation are examples of these processes as they regulate different mechanisms that mediate neuronal demise including necrosis, apoptosis, necroptosis, pyroptosis and autophagy. In this review, we discuss recent findings on balanced regulation and their involvement in neuronal death. PMID- 26376103 TI - Membrane protein isolation and identification by covalent binding for proteome research. AB - A novel method to achieve highly efficient identification of membrane proteins (MPs) has been developed based on a covalent binding (CB) strategy. For this purpose, magnetic nanoparticles coated with a PEG layer were synthesized. The PEG chain end was functionalized to form the PEG-tresyl group, which is an octopus like long arm to capture the free amino groups of MPs. The long arm could be used to bind proteins in a high concentration of the SDS medium. Then, the SDS and interfering substances were completely depleted by washing. The CB proteins could form a molecular monolayer on the surface of the nanoparticles in the denatured state, which was significantly favorable for the proteolysis of MPs. Therefore, isolation with CB and highly efficient digestion resulted in a larger scale of MPs. The method has been verified by a proteome identification of mouse liver samples. A total of 2946 MPs were identified in an MP fraction. A total of 1505 proteins were characterized as integral MPs, and 735 MPs were identified beyond the largest database summarized by PeptideAtlas. This approach has great potential for membrane proteome research. PMID- 26376104 TI - Protective role of extracts of grape skin and grape flesh on ethanol-induced oxidative stress, inflammation and histological alterations in rat brain. AB - Ethanol consumption has deleterious effects on all organs and especially on brain. In our study, the radical scavenging properties of grape skin and grape flesh (contains natural antioxidants like polyphenols) was determined in vitro and for in vivo studies, male Wistar rats (16-18 week-old) and 100-120 gm weight were divided in five groups of six animals each. One group were fed with ethanol (1.6 gm/kg body weight), while second group were fed with ethanol (1.6 g/kg body weight) and grape skin extract (2.5 g/kg body weight), the third group were fed with ethanol (1.6 g/kg body weight) and grape flesh extract, daily once for 12 weeks, while the fourth group were fed with ethanol (1.6 g/kg body weight) and tocopheryl acetate (80 mg/kg/day) daily once for 12 weeks. Results of in vitro studies indicate that grape skin extracts showed significant radical scavenging properties (ROS). There was also significantly alteration of serum cytokines in our study. PMID- 26376105 TI - Effect of bisphenol A on blood glucose, lipid profile and oxidative stress indices in adult male mice. AB - Bisphenol A (BPA), an endocrine-disrupting chemical, has been considered as a possible risk factor for diabetes and its complications. However, the underlying mechanisms of BPA-induced diabetes are not clear. The present study was performed to evaluate the effects of BPA on the hyperglycemia, lipid abnormalities and oxidative stress. In this study, the mice were divided into three groups of six animals each: One group as a control (C) and two other groups which exposed to 0.5 and 2 mg/kg concentrations of BPA. BPA powder was dissolved in sterile extra virgin olive oil and injected intraperitoneally to the tested groups, while the control group only received pure olive oil for 4 weeks. After 4 weeks, the changes of glucose, lipid profile reduced, total protein, glutathione (GSH), malondialdehyde (MDA), total antioxidant status (TAS), catalase (CAT) and super oxide dismutase (SOD) were determined in serum and pancreas. The results indicated that BPA dose-dependently increased the levels of blood glucose, lipid profile and MDA in the tested groups compared with the control group (p < 0.001). BPA reduced significantly the levels of HDL-C and GSH in dose-dependent manner (p < 0.001). BPA injection increased the levels of MDA and decreased the levels of GSH and TAS, and also the activities of SOD and CAT in the pancreas of exposed mice compared with the control group (p < 0.05). In addition, body weight increased in the mice exposed to BPA compare to control animals. These results suggest that BPA exposure might induce hyperglycemia and its complications in adult male mice by induction of oxidative stress. PMID- 26376106 TI - Acute angle closure glaucoma precipitated by olanzapine. PMID- 26376107 TI - Mini-Addenbrooke's cognitive examination diagnostic accuracy for dementia: reproducibility study. PMID- 26376108 TI - Lunisolar tidal force and its relationship to chlorophyll fluorescence in Arabidopsis thaliana. AB - The yield of chlorophyll fluorescence Ft was measured in leaves of Arabidopsis thaliana over periods of several days under conditions of continuous illumination (LL) without the application of saturating light pulses. After linearization of the time series of the chlorophyll fluorescence yield (DeltaFt), oscillations became apparent with periodicities in the circatidal range. Alignments of these linearized time series DeltaFt with the lunisolar tidal acceleration revealed high degrees of synchrony and phase congruence. Similar congruence with the lunisolar tide was obtained with the linearized quantum yield of PSII (DeltaFII), recorded after application of saturating light pulses. These findings strongly suggest that there is an exogenous timekeeper which is a stimulus for the oscillations detected in both the linearized yield of chlorophyll fluorescence (DeltaFt) and the linearized quantum yield of PSII (DeltaFII). PMID- 26376109 TI - Protective effect of astragaloside IV on lipopolysaccharide-induced cardiac dysfunction via downregulation of inflammatory signaling in mice. AB - CONTEXT: Astragaloside IV (ASI) is a major and active saponin derivative of Astragalus membranaceus (Fisch) Bge. The anti-inflammatory properties of ASI are important for its cardioprotective effects. However, the molecular mechanisms of the protective effect of ASI on lipopolysaccharide (LPS)-induced cardiac dysfunction is yet to be elucidated. OBJECTIVE: This study was designed to investigate the therapeutic effects and possible mechanisms of ASI against LPS induced septic cardiac dysfunction and inflammation in mice. MATERIALS AND METHODS: Mice were intraperitoneally injected with ASI (20 mg/kg) for 1 week before LPS challenge (10 mg/kg, i.p.). Left ventricular performance and morphology were analyzed using echocardiography 6 h after LPS induction. Activities of lactate dehydrogenase (LDH) in serum were measured and serum levels of cardiac troponin I (cTnI) were quantified by ELISA. Serum levels of tumor necrosis factor-alpha (TNF-alpha), monocyte chemotactic protein 1 (MCP-1), interleukin-6 (IL-6) and IL-1beta were also quantified by ELISA. The protein expressions of NF-kB p65 and p-AKT in heart tissues were detected using Western blot analysis. RESULTS: LPS administration deteriorated cardiac function and was attenuated by ASI pretreatment. ASI attenuated LPS-induced the increase of LDH and cTnI activities in mice. ASI also prevented NF-kB activation and subsequent myocardial inflammatory responses in endotoxemic mice. The effects of ASI were closely associated with the phosphatidylinositol-3-kinase (PI3K/AKT) signaling pathway, as characterized by ASI-induced activation in phospho-Akt. ASI also extended the lifespan of toxemic mice. CONCLUSION: ASI significantly attenuated LPS-induced cardiac dysfunction and inflammatory mediator production by inhibiting NF-kB and activating PI3K/AKT signaling pathway. PMID- 26376110 TI - Dietary interventions for mineral and bone disorder in people with chronic kidney disease. AB - BACKGROUND: Chronic kidney disease-mineral and bone disorder (CKD-MBD) is a systemic dysfunction of mineral and bone metabolism in people with CKD. Recent research shows that phosphate retention plays a significant role in the development of CKD-MBD. Compared with drug therapies, dietary interventions may be simple, inexpensive and feasible for phosphate retention. However, there is little evidence to support these interventions. OBJECTIVES: Our objective was to assess the benefits and harms of any dietary intervention for preventing and treating CKD-MBD. SEARCH METHODS: We searched Cochrane Kidney and Transplant's Specialised Register to 27 August 2015 through contact with the Trials' Search Co ordinator using search terms relevant to this review. We also searched the Chinese Biomedicine Database (CBM) (1976 to August 2015), China Knowledge Resource Integrated Database (CNKI) (1979 to August 2015), and VIP (1989 to August 2015). SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi RCTs looking at dietary interventions for prevention or treatment of CKD-MBD were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two authors independently assessed the eligibility, methodological quality, and extracted data. Continuous outcomes (serum calcium level, serum phosphorus level, calcium * phosphate product, parathyroid hormone (PTH), fibroblast growth factor 23 (FGF-23) and alkaline phosphatase) were expressed as mean difference (MD) with 95% confidence interval (CI). Dichotomous outcomes (mortality) were expressed as risk ratio (RR) with 95% CI. We used a random-effects model to meta-analyse studies. MAIN RESULTS: Nine studies were included in this review which analysed 634 participants. Study duration ranged from 4 to 24 weeks. The interventions included calcium-enriched bread, low phosphorus intake, low protein intake, very low protein intake, post haemodialysis supplements and hypolipaemic diet. Only one study reported death; none of the included studies reported cardiovascular events or fractures. There was insufficient reporting of design and methodological aspects among the included studies to enable robust assessment of risk of bias.There was limited and low-quality evidence to indicate that calcium enriched bread increased serum calcium (1 study, 53 participants: MD -0.16 mmol/L, 95% CI -0.51 to -0.31), decreased serum phosphorus (53 participants: MD 0.41 mmol/L, 95% CI -0.51 to -0.31) and decreased the calcium * phosphate product (53 participants: MD -0.62 mmol2/L2, 95% CI -0.77 to -0.47).Very low protein intake was not superior to conventional low protein intake in terms of effect on serum phosphorus (2 studies, 41 participants: MD -0.12 mmol/L, 95% CI -0.50 to 0.25), serum calcium (MD 0.00 mmol/L, 95% CI -0.17 to 0.17), or alkaline phosphatase (MD -22.00 U/L, 95% CI -78.25 to 34.25). PTH was significantly lower in the very low protein intake group (2 studies, 41 participants: MD -69.64 pmol/L, 95% CI -139.83 to 0.54).One study reported no significant difference in the number of deaths between low phosphorus intake and normal diet (279 participants: RR 0.18, 95% CI 0.01 to 3.82). Low phosphorus intake decreased serum phosphorus (2 studies, 359 participants: MD -0.18 mmol/L, 95% CI -0.29 to 0.07; I(2) = 0%).One study reported post-haemodialysis supplements did not increase serum phosphorus compared to normal diet (40 participants: MD 0.12 mmol/L, 95% CI -0.24 to 0.49).One study reported low phosphorus intake plus lanthanum carbonate significantly decreased FGF-23 (19 participants: MD -333.80 RU/mL, 95% CI -526.60 to -141.00), but did not decrease serum phosphorus (19 participants: MD -0.10 mg/dL, 95% CI -0.38 to 0.58) or PTH (19 participants: MD 31.60 pg/mL, 95% CI -29.82 to 93.02). AUTHORS' CONCLUSIONS: There was limited low quality evidence to indicate that dietary interventions (calcium-enriched bread or low phosphorus/protein intake) may positively affect CKD-MBD by increasing serum calcium, decreasing serum phosphorus, the calcium * phosphate product and FGF-23. Large and well-designed RCTs are needed to evaluate the effects of various interventions for people with CKD-MBD. PMID- 26376112 TI - The Effect of Postexercise Milk Protein Intake on Rehydration of Children. AB - PURPOSE: In adults, rehydration after exercise in the heat can be enhanced with a protein-containing beverage; however, whether this applies to children remains unknown. This study examined the effect of milk protein intake on postexercise rehydration in children. METHOD: Fifteen children (10-12 years) performed three exercise trials in the heat (34.4 +/- 0.2 degrees C, 47.9 +/- 1.1% relative humidity). In a randomized, counterbalanced crossover design, participants consumed iso-caloric and electrolyte-matched beverages containing 0 g (CONT), 0.76 g (Lo-PRO) or 1.5 g (Hi-PRO) of milk protein/100 mL in a volume equal to 150% of their body mass (BM) loss during exercise. BM was then assessed over 4 h of recovery. RESULTS: Fluid balance demonstrated a significant condition * time interaction (p = .012) throughout recovery; Hi-PRO was less negative than CONT at 2 hr (p = .01) and tended to be less negative at 3 h (p = .07). Compared with CONT, beverage retention was enhanced by Hi-PRO at 2 h (p < .05). CONCLUSION: A postexercise beverage containing milk protein can favorably affect fluid retention in children. Further research is needed to determine the optimal volume and composition of a rehydration beverage for complete restoration of fluid balance. PMID- 26376113 TI - Clinical Research Abstracts of the British Equine Veterinary Association Congress 2015. AB - REASONS FOR PERFORMING STUDY: Blackthorn (Prunus spinosus) is recognised as causing infections and tissue reactions. OBJECTIVES: To describe the presentation, diagnosis, treatment and outcome of blackthorn plant thorn synovitis in the horse. STUDY DESIGN: Case series. METHODS: All cases in this prospective study presented with acute onset synovitis within 24 h of thorn penetration, had a standardised clinical assessment, surgical treatment and aftercare. Surgical treatment was performed within 24 h of presentation under general anaesthesia, using a 2-stage procedure: Stage 1: perisynovial technique. Ultrasound guided placement of a 20 gauge 35 mm needle marker that is used as a guide for electrosurgical dissection onto perisynovial thorn fragments. Stage 2: endoscopic technique. Using standard and novel portals to locate and remove thorn fragments and debris from synovial structures. RESULTS: Thirty-five cases met the study inclusion criteria over a 24 month period. Mean lameness score on presentation was 4/5 (range 1-5). The most commonly affected structures were fetlock joints (11/35) and tendon sheaths (10/35). Mean synovial fluid total protein was 50.5 g/l (range 18-116), and TNCC was 158 x 10(9) (range 21-412) on presentation and 12 x 10(9) (range 1-46) at 48 h post operatively. All synovial fluid cultures were negative. All horses were sound (grade 0) at 5 days post operatively and all returned to full work. CONCLUSIONS: There are a limited number of case series of blackthorn injury in humans; however, the consensus is that surgical treatment is required for a successful outcome. The 2-stage surgical procedure described, achieved accurate identification and removal of thorn material in all cases. In contrast to previous studies on synovial sepsis, these cases had a positive outcome despite high pre- and post operative synovial fluid total protein and TNCC. These findings suggest that thorn synovitis cases have a different aetiology from synovitis originating from sepsis or contamination. Ethical animal research: The study was reviewed and approved by the Ethics Committee, School of Veterinary Medicine and Science, University of Nottingham. Owners gave informed consent for their horses' inclusion in the study. SOURCE OF FUNDING: None. Competing interests: None declared. PMID- 26376111 TI - Monoclonal antibody against macrophage colony-stimulating factor suppresses circulating monocytes and tissue macrophage function but does not alter cell infiltration/activation in cutaneous lesions or clinical outcomes in patients with cutaneous lupus erythematosus. AB - This study's objective was to assess the effects of PD-0360324, a fully human immunoglobulin G2 monoclonal antibody against macrophage colony-stimulating factor in cutaneous lupus erythematosus (CLE). Patients with active subacute CLE or discoid lupus erythematosus were randomized to receive 100 or 150 mg PD 0360324 or placebo via intravenous infusion every 2 weeks for 3 months. Blood and urine samples were obtained pre- and post-treatment to analyse pharmacokinetics and pharmacodynamic changes in CD14(+) CD16(+) monocytes, urinary N-terminal telopeptide (uNTX), alanine/aspartate aminotransferases (ALT/AST) and creatine kinase (CK); tissue biopsy samples were taken to evaluate macrophage populations and T cells using immunohistochemistry. Clinical efficacy assessments included the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI). Among 28 randomized/analysed patients, peak/trough plasma concentrations increased in a greater-than-dose-proportional manner with dose increases from 100 to 150 mg. Statistically significant differences were observed between active treatment and placebo groups in changes from baseline in CD14(+) CD16(+) cells, uNTX, ALT, AST and CK levels at most time-points. The numbers, density and activation states of tissue macrophages and T cells did not change from baseline to treatment end. No between-group differences were seen in CLASI. Patients receiving PD-0360324 reported significantly more adverse events than those receiving placebo, but no serious adverse events. In patients with CLE, 100 and 150 mg PD-0360324 every 2 weeks for 3 months suppressed a subset of circulating monocytes and altered activity of some tissue macrophages without affecting cell populations in CLE skin lesions or improving clinical end-points. PMID- 26376114 TI - Zerovalent iron and iron(VI): Effective means for the removal of psychoactive pharmaceuticals and illicit drugs from wastewaters. AB - Herein we report the analysis of 27 selected psychoactive compounds found in the wastewater of the largest suburb in the eastern part of Central Europe Bratislava Petrzalka, Slovakia. Thirteen of them (MDMA, methamphetamine, amphetamine, THC COOH, benzoylecgonine, codeine, tramadol, venlafaxine, oxazepam, citalopram, methadone, EDDP, cocaine) were found in concentrations above 30 ng/L. These compoundswere selected for further monitoring. The possibility of complete degradation of these 13 substances by zerovalent iron and iron(VI) was studied in thewastewater from the Petrzalka treatment plant. During the week the concentration of themajority of the studied compounds inwastewaterwas stable. Concentrations of MDMA, cocaine, tramadol, and oxazepam reached significantly higher levels during the weekend.Only about 10% removal efficiency for tramadol, venlafaxine, oxazepam, MDMA, citalopram, methadone, and EDDP was observed at the treatment plant. In contrast, methamphetamine, amphetamine, and codeine were removed with 68%, 83%, and 53% efficiency, respectively. The degradation of synthetic drugs (methamphetamine, cocaine, MDMA) in wastewater is limited, while cannabis (of natural biological origin) is degradedwith efficiency greater than 90%. After utilization of the Fenton reaction, its modification, and use of ferrate(VI), a high efficiency of eliminating all of these substances to values below the limit of detection was achieved. PMID- 26376115 TI - A Phase I Study of Clofarabine With Multiagent Chemotherapy in Childhood High Risk Relapse of Acute Lymphoblastic Leukemia (VANDEVOL Study of the French SFCE Acute Leukemia Committee). AB - BACKGROUND: Current outcome of very early relapse of acute lymphoblastic leukemia (ALL) in children remains poor. As a single agent, clofarabine provided a response rate of 26% in childhood ALL second relapse and, in combination with cyclophosphamide and etoposide, a 44% complete remission and complete remission without platelet recovery (CR+CRp) rate. Further multi-drug combinations need to be investigated. We used the VANDA regimen as a template, cytarabine being replaced by clofarabine. PATIENTS AND METHODS: A phase I study combining escalating doses of clofarabine (25% increments from 20 to 40 mg/m(2)/d) with fixed doses of mitoxantrone, etoposide, asparaginase, and dexamethasone was undertaken in children presenting with very early or second or post-transplant ALL relapse. RESULTS: Twenty patients were enrolled, 19 were evaluable. Four patients had previously been allografted. Dose-limiting toxicity (DLT) appeared at dose level 3 (32 mg/m(2)), one out of six patients experienced a liver DLT. At dose level 4 (40 mg/m(2)), four DLT occurred (two fungal infection and two liver DLT). The maximum tolerated dose (MTD) of clofarabine was thus determined to be 32 mg/m(2). There was no toxic death. Eleven (57.9%) patients achieved a CR. Six patients proceeded to allogeneic stem cell transplantation. CONCLUSION: Clofarabine MTD was 32 mg/m(2)/d in this combination which appeared feasible and effective in this population. PMID- 26376116 TI - Facile fabrication of egg white macroporous sponges for tissue regeneration. AB - The availability of 3D sponges combining proper biochemical, biophysical, and biomechanical properties with enhanced capacity of in vivo engraftment and vascularization is crucial in regenerative medicine. A simple process is developed to generate macroporous scaffolds with a well-defined architecture of interconnected pores from chicken egg white (EW), a material with protein- and growth factor-binding features which has not yet been employed in regenerative medicine. The physicomechanical properties and degradation rates of the scaffold are finely tuned by using varying concentrations of the cross-linker, 1-ethyl-3 (3-dimethylaminopropyl) carbodiimide hydrochloride, without alteration of the biochemical traits. In vitro, EW scaffolds supported active metabolism, proliferation, and migration of human dermal fibroblasts, thereby generating uniform cellular constructs. In vivo, subcutaneous implantation in mice reveals negligible immune reaction and efficient cell and tissue ingrowth. Angiogenesis into EW scaffolds is enhanced as compared to standard collagen type I sponges used as reference material, likely due to significantly higher adsorption of the proangiogenic factor vascular endothelial growth factor. In summary, a material is presented derived by facile processing of a highly abundant natural product. Due to the efficient subcutaneous engraftment capacity, the sponges can find utilization for soft tissue regeneration. PMID- 26376117 TI - Connexin43-containing gap junctions potentiate extracellular Ca2+-induced odontoblastic differentiation of human dental pulp stem cells via Erk1/2. AB - Extracellular Ca(2+) can promote dentin sialophosphoprotein (DSPP) expression and odontoblastic differentiation of dental pulp stem cells (DPSCs). Gap junctions mediated by connexin43 (Cx43) allow diffusion of small molecules (such as Ca(2+)) among cells to regulate cell-to-cell communications. However, it is unclear whether Cx43 is required for the Ca(2+)-induced cell differentiation. Here, we found that the influx of extracellular Ca(2+) through L-type Ca(2+) channels increases intracellular free Ca(2+) levels to promote DSPP expression. Cx43 overexpression potentiated the extracellular Ca(2+)-induced DSPP expression via Erk1/2. Flow cytometry analyses showed that Cx43 increased the percentage of p Erk1/2 positive cells in response to Ca(2+), indicating that Cx43 in DPSCs possibly acts as a traditional gap junction channel, which permits the sharing of signals among coupled cells to make more DPSCs respond to Ca(2+). Furthermore, inhibition of Cx43 function and gap junction communication decreased Ca(2+) induced the expression of DSPP, suggesting that cell-to-cell contacts are required for Cx43 to promote the Ca(2+)-induced cell differentiation. Similarly, the study performed on DPSCs cultured at low-density and high-density revealed that intercellular contacts are required to potentiate Erk1/2 activity and DSPP expression. In total, this study indicates that Cx43 increases Ca(2+)-induced DSPP expression and odontoblastic differentiation of DPSCs via Erk1/2 through gap junction-mediated cell-to-cell contacts. PMID- 26376118 TI - Enhanced expression of CD31/platelet endothelial cell adhesion molecule 1 (PECAM1) correlates with hypoxia inducible factor-1 alpha (HIF-1alpha) in human glioblastoma multiforme. AB - Glioblastoma multiforme (GBM) is characterized by numerous abnormal blood vessels, which rapidly proliferate and invade brain tissue and express different angiogenic factors. In this study we have investigated whether the expression levels of CD31/ PECAM1 are deregulated in human GBM tissue specimens and we have also correlated the expression levels of CD31/PECAM1 with those of HIF-1alpha. Finally, we have established a correlation between the expression levels of CD31/PECAM1 and HIF-1alpha, and those of two other biomarkers, namely N-cadherin and ADAM-10, of aggressiveness in the same tumors. Results have shown an increased expression of CD31/PECAM1 correlated to HIF-1alpha expression, confirming evidence demonstrating that different types of tumor are able to trigger aberrant angiogenesis through HIF-1alpha. Moreover, we also established a further correlation among CD31/PECAM1 and HIF-1alpha and N-cadherin and ADAM-10, two other markers of aggressiveness in the same tumors. PMID- 26376120 TI - Preparation and testing of a solid secondary plasticizer for PVC produced by chemical degradation of post-consumer PET. AB - Post-consumer poly(ethylene therephthalate) (PET) obtained from milled water bottles was chemically degraded by glycolysis, using suitable amounts of diethylene glycol (DEG) and Ca/Zn stearate as catalyst system. The process was carried out by employing a melt mixer as the chemical reactor, which is the facility generally used for plastic compounding. The degraded PET products were first characterized from structural and thermal point of view by Fourier transform infrared spectroscopy (FTIR), Proton nuclear magnetic resonance ((1)H NMR), Size exclusion chromatography (SEC) Differential scanning calorimetry (DSC) and Thermogravimetric analysis (TGA), and thereafter used alone or together with di(2-ethylhexyl) phthalate (DEHP) in poly(vinyl chloride) PVC formulations. The plasticization was, in fact, accomplished by using a binary system consisting of DEHP as primary plasticizer and a degraded PET product as secondary plasticizer (SP). The obtained materials were characterized through the main methods used to assess flexible PVC compounds: hardness in Shore A scale, thermal properties and quantitative migration of the plasticizer. The solid secondary plasticizer obtained from post-consumer PET improves both the processing characteristics and the thermal stability of the final flexible PVC compounds while maintaining their hardness within the top values of the Shore A scale. In addition, a considerable reduction of the plasticizers migration (23%) was obtained by optimizing the formulation. PMID- 26376121 TI - Out with the old, out with the new--The effect of transitions in TVs and monitors technology on consumption and WEEE generation in Sweden 1996-2014. AB - The recycling of Waste Electrical and Electronic Equipment (WEEE) is important due to its content of valuable and hazardous compounds. This study investigates the case of the recent technology change within television sets (TVs) and monitors, its impact on the generation of WEEE, and the implications for the recycling industry. In particular, material flow analysis for the time series of 1996-2014 for TVs and monitors by type of technology (CRT, Plasma and LCD) in physical units is combined with empirical data on product lifespans. The number of consumed TVs and monitors has grown exponentially. As a result, despite a 3 fold reduction in the weight of the products, the weight of the corresponding WEEE is also growing exponentially. Out with the old, out with the new - a peak in WEEE from both CRT and flat-screen displays is expected during 2014-2020, due to the simultaneous obsolesce of the last wave of CRT products and the short lived flat-screen products that substituted the CRTs. The lifespans of LCD and LED TVs were found to be three times shorter than of the CRT TVs, with many TVs discarded while still functional. This is the consequence of two events - replacement of the CRT TVs in combination with lifestyle purchases of TVs, i.e. the premature replacement of flat-screen displays with new sets with extra-large screens and/or new features. The throughput of TVs and monitors consumed has been estimated annually from 2014 until 2040, by quantity and type of device, as well as by component and material type. The annual economic value of the corresponding secondary materials, by material type, has also been estimated. The point in time when the final disposal of CRT products is likely to take place has been identified and should be noted by the recycling industry. Among the important contributions of this study to the accounting and predicting of amounts and types of WEEE are the lifespan distributions, size and weight distributions, and material composition for TVs and monitors of different technology. Directions for method application in other countries are given. PMID- 26376122 TI - Substitution potentials of recycled HDPE and wood particles from post-consumer packaging waste in Wood-Plastic Composites. AB - The market share of Wood-Plastic Composites (WPC) is small but expected to grow sharply in Europe. This raises some concerns about suitable wood particles needed in the wood-based panels industry in Europe. Concerns are stimulated by the competition between the promotion of wooden products through the European Bioeconomy Strategy and wood as an energy carrier through the Renewable Energy Directive. Cascade use of resources and valorisation of waste are potential strategies to overcome resource scarcity. Under experimental design conditions, WPC made from post-consumer recycled wood and plastic (HDPE) were compared to WPC made from virgin resources. Wood content in the polymer matrix was raised in two steps from 0% to 30% and 60%. Mechanical and physical properties and colour differences were characterized. The feasibility of using cascaded resources for WPC is discussed. Results indicate the technical and economic feasibility of using recycled HDPE from packaging waste for WPC. Based on technical properties, 30% recycled wood content for WPC is feasible, but economic and political barriers of efficient cascading of biomass need to be overcome. PMID- 26376123 TI - Targeted Proteomics of Human Metapneumovirus in Clinical Samples and Viral Cultures. AB - The rapid, sensitive, and specific identification of infectious pathogens from clinical isolates is a critical need in the hospital setting. Mass spectrometry (MS) has been widely adopted for identification of bacterial pathogens, although polymerase chain reaction remains the mainstay for the identification of viral pathogens. Here, we explored the capability of MS for the detection of human metapneumovirus (HMPV), a common cause of respiratory tract infections in children. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) sequencing of a single HMPV reference strain (CAN97-83) was used to develop a multiple reaction monitoring (MRM) assay that employed stable isotope-labeled peptide internal standards for quantitation of HMPV. Using this assay, we confirmed the presence of HMPV in viral cultures from 10 infected patients and further assigned genetic lineage based on the presence/absence of variant peptides belonging to the viral matrix and nucleoproteins. Similar results were achieved for primary clinical samples (nasopharyngeal aspirates) from the same individuals. As validation, virus lineages, and variant coding sequences, were confirmed by next-generation sequencing of viral RNA obtained from the culture samples. Finally, separate dilution series of HMPV A and B lineages were used to further refine and assess the robustness of the assay and to determine limits of detection in nasopharyngeal aspirates. Our results demonstrate the applicability of MRM for identification of HMPV, and assignment of genetic lineage, from both viral cultures and clinical samples. More generally, this approach should prove tractable as an alternative to nucleic-acid based sequencing for the multiplexed identification of respiratory virus infections. PMID- 26376124 TI - Sleep Apnea Symptoms as a Predictor of Fatigue in an Urban HIV Clinic. AB - Fatigue is common among persons living with HIV (PLWH), and risk factors for obstructive sleep apnea (OSA) such as older age and obesity are increasingly prevalent. Studies of OSA among PLWH are lacking, so we aimed to characterize OSA symptoms and associated clinical consequences (e.g., fatigue) among a contemporary population of PLWH. Self-administered surveys containing 23 items that included self-reported snoring, witnessed apneas, estimated sleep duration, the Epworth Sleepiness Score (ESS), and the FACIT-Fatigue score were mailed to PLWH receiving care at an urban HIV clinic. Clinical/demographic data were collected from the medical record. Multivariable linear regression models were created to study relationships between fatigue, clinical variables, and OSA symptoms. Of 535 surveys, 203 (38%) responded. Eight patients (3.9%) had known OSA. Among those without known OSA, mean respondent characteristics included: age 47 years; 80% male, 41% African American, 48% Caucasian, BMI 26.4 kg/m(2), duration of HIV diagnosis 12 years, 93% on antiretroviral therapy, and 81% with <50 HIV RNA copies/mL. 27% reported snoring, 24% reported witnessed apneas, and 38% had excessive daytime sleepiness. Witnessed apnea was the strongest independent predictor of fatigue (lower FACIT-Fatigue score; beta = -6.49; p < 0.001); this difference of 6.49 points exceeds the accepted minimal clinically important difference of 3.0 points. Other predictors included opioid use (beta = 5.53; p < 0.001), depression (beta = -4.18; p = 0.02), antidepressant use (beta = -4.25; p = 0.02), and sleep duration < 6 h (beta = -3.42; p = 0.02). Our data strongly support the need for increased efforts directed at OSA screening and treatment in PLWH. PMID- 26376125 TI - Subchondral plate porosity colocalizes with the point of mechanical load during ambulation in a rat knee model of post-traumatic osteoarthritis. AB - OBJECTIVE: This study investigated the association between spatiotemporal cartilage-subchondral bone plate alterations and mechanical load during ambulation in an experimental rat model of destabilized medial meniscus (DMM). DESIGN: Twelve-week-old Wistar rats (n = 38) underwent DMM surgery on the right knee and sham surgery on the left knee. At 2 and 4 weeks after surgery, subchondral bone changes were evaluated via micro-computed tomography with various knee flexion angles to simulate weight-bearing during rat ambulation under a 3-dimensional motion capture apparatus. Additionally, the biomechanical properties, histology, and ultrastructure of the medial tibia and femoral condyle were evaluated. RESULTS: Focal subchondral bone plate perforations were confirmed in the medial tibia within 2 weeks after surgery and were aggravated rapidly 2 weeks later. This subchondral plate porosity colocalized with articular cartilage lesions as confirmed by histology and scanning electron microscopy, and coincided with the likely point of contact between the posterior femoral condyle and tibial plateau during ambulation. Biomechanical properties were confirmed at the medial tibia, at which stiffness was reduced to approximately half that of the sham operated knee at 4 weeks after surgery. CONCLUSIONS: Cartilage-subchondral bone plate alterations localized in the region of the point of mechanical load during ambulation in DMM-operated knees, at which the mechanical integrity of cartilage was impaired. These results indicate that DMM-induced increases in mechanical load play an important role in the pathogenesis of early post-traumatic osteoarthritis (OA), and it might accelerate the development of the disease via cartilage-subchondral bone plate crosstalk through increased subchondral plate perforations. PMID- 26376126 TI - Validation of a questionnaire about the perception of occupational biohazard in Spanish companies. AB - OBJECTIVES: The aim of this work was to develop, validate and test a new questionnaire to assess the biological risk in workers with intentional or unintentional exposure to biological agents. METHODS: A questionnaire including 34 questions was developed to study the perception of workers against occupational biohazard. Content Validity Index (CVI) and Content Validity Ratio (CVR) were calculated for the analysis of content validity. A pilot study was carried out with 60 workers from 17 companies performing analysis of Cronbach's alpha to assess the internal consistency or reliability. RESULTS: A total of 518 workers from 51 Spanish companies in which there is exposure to biological agents participated in the study yielding a response rate of 90%. The final questionnaire obtained a Cronbach's alpha > 0.759 with a stable test-retest result. The questionnaire validation demonstrates that it could be used to evaluate the biological risks and help the prevention of occupational accidents and diseases. DISCUSSION: This study has validated the need to evaluate worker's perception against occupational risks, as well as the application of prevention methods and protective equipment. It is a first step towards developing an occupational biohazards assessment method including all the requirements set by the European Health and Safety Strategy 2013-2020. PMID- 26376127 TI - Treatment of Dural Carotid-Cavernous Fistulas via the Medial Ophthalmic Vein. AB - AIM: To present a novel approach to treatment of dural carotid-cavernous fistulas via the medial ophthalmic vein. DESIGN: Retrospective case series. MATERIAL AND METHODS: In this retrospective case series, we present 2 patients (3 eyes) with Type C dural CCFs, who had failed cannulation via the conventional transfemoral route and the transorbital superior ophthalmic vein approach. They subsequently underwent CCF occlusion via an anterior orbital approach through the medial ophthalmic veins, at the Department of Ophthalmology, National University Hospital Singapore. CCF occlusion was confirmed intraoperatively using angiography. Both patients were evaluated postoperatively for best-corrected visual acuity and resolution of clinical signs and symptoms. RESULTS: Successful occlusion of CCFs via the medial ophthalmic veins were achieved in all three orbits, with excellent visual and cosmetic outcomes postoperatively. CONCLUSION: Dural CCFs may potentially lead to severe visual dysfunction and should be diagnosed and treated promptly. When all venous routes have been exhausted, the transorbital approach via the medial ophthalmic vein remains an excellent and viable alternative to access the fistula. Close cooperation between the orbital, anesthetic and radiological teams is essential in ensuring success of the operation. PMID- 26376128 TI - A comparison of opioid-related adverse events with fentanyl iontophoretic transdermal system versus morphine intravenous patient-controlled analgesia in acute postoperative pain. AB - OBJECTIVE: This analysis compared opioid-related adverse events (ORADEs) observed with fentanyl iontophoretic transdermal system (ITS) versus morphine intravenous (iv.) patient-controlled analgesia (PCA) in the management of postoperative pain. METHODS: Safety data from four Phase IIIB randomized, active-comparator trials were pooled for this analysis (n = 1288 fentanyl ITS and 1313 morphine iv. PCA patients). Treatment-emergent adverse events were collected via spontaneous report. In this post hoc analysis, ORADEs were defined as apnea, confusion, constipation, dyspnea, hypotension, hypoventilation, hypoxia, ileus, nausea, pruritus, somnolence, tachycardia, urinary retention and vomiting. Odds ratios (OR) and 95% CI were calculated for all ORADEs and p-values were based on logistic regression with treatment as effect. RESULTS: There were fewer patients in the fentanyl ITS group compared with the morphine iv. PCA group who experienced at least one ORADE (52.7 vs 59.1%, respectively; OR: 0.772: 95% CI: 0.661-0.901; p = 0.0011). The ORADEs that occurred less frequently in the fentanyl ITS group than in the morphine iv. PCA group included hypotension (3.7 vs 5.5%, respectively; OR: 0.667; 95% CI: 0.459-0.969; p = 0.0338), hypoventilation (0.9 vs 1.9%, respectively; OR: 0.444; 95% CI: 0.217-0.906; p = 0.0256), nausea (40.3 vs 44.5%, respectively; OR: 0.842; 95% CI: 0.721-0.984; p = 0.0310), pruritus (5.5 vs 9.4%, respectively; OR: 0.559; 95% CI: 0.413-0.757; p = 0.0002) and tachycardia (1.6 vs 2.8%, respectively; OR: 0.489; 95% CI: 0.277 0.863; p = 0.0136). No ORADEs occurred more frequently in the fentanyl ITS group compared with the morphine iv. PCA group. CONCLUSION: Fentanyl ITS, in the management of acute postoperative pain, offered safety advantages in terms of ORADEs compared with morphine iv. PCA. PMID- 26376129 TI - The phenotypes of podocytes and parietal epithelial cells may overlap in diabetic nephropathy. AB - Reversal of diabetic nephropathy (DN) has been achieved in humans and mice, but only rarely and under special circumstances. As progression of DN is related to podocyte loss, reversal of DN requires restoration of podocytes. Here, we identified and quantified potential glomerular progenitor cells that could be a source for restored podocytes. DN was identified in 31 human renal biopsy cases and separated into morphologically early or advanced lesions. Markers of podocytes (WT-1, p57), parietal epithelial cells (PECs) (claudin-1), and cell proliferation (Ki-67) were identified by immunohistochemistry. Podocyte density was progressively reduced with DN. Cells marking as podocytes (p57) were present infrequently on Bowman's capsule in controls, but significantly increased in histologically early DN. Ki-67-expressing cells were identified on the glomerular tuft and Bowman's capsule in DN, but rarely in controls. Cells marking as PECs were present on the glomerular tuft, particularly in morphologically advanced DN. These findings show evidence of phenotypic plasticity in podocyte and PEC populations and are consistent with studies in the BTBR ob/ob murine model in which reversibility of DN occurs with podocytes potentially regenerating from PEC precursors. Thus, our findings support, but do not prove, that podocytes may regenerate from PEC progenitors in human DN. If so, progression of DN may represent a modifiable net balance between podocyte loss and regeneration. PMID- 26376130 TI - Patiromer induces rapid and sustained potassium lowering in patients with chronic kidney disease and hyperkalemia. AB - Patients with chronic kidney disease (CKD) have a high risk of hyperkalemia, which increases mortality and can lead to renin-angiotensin-aldosterone system inhibitor (RAASi) dose reduction or discontinuation. Patiromer, a nonabsorbed potassium binder, has been shown to normalize serum potassium in patients with CKD and hyperkalemia on RAASi. Here, patiromer's onset of action was determined in patients with CKD and hyperkalemia taking at least one RAASi. After a 3-day potassium- and sodium-restricted diet in an inpatient research unit, those with sustained hyperkalemia (serum potassium 5.5 - under 6.5 mEq/l) received patiromer 8.4 g/dose with morning and evening meals for a total of four doses. Serum potassium was assessed at baseline (0 h), 4 h postdose, then every 2-4 h to 48 h, at 58 h, and during outpatient follow-up. Mean baseline serum potassium was 5.93 mEq/l and was significantly reduced by 7 h after the first dose and at all subsequent times through 48 h. Significantly, mean serum potassium under 5.5 mEq/l was achieved within 20 h. At 48 h (14 h after last dose), there was a significant mean reduction of 0.75 mEq/l. Serum potassium did not increase before the next dose or for 24 h after the last dose. Patiromer was well tolerated, without serious adverse events and no withdrawals. The most common gastrointestinal adverse event was mild constipation in two patients. No hypokalemia (serum potassium under 3.5 mEq/l) was observed. Thus, patiromer induced an early and sustained reduction in serum potassium and was well tolerated in patients with CKD and sustained hyperkalemia on RAASis. PMID- 26376132 TI - The emerging role of complement inhibitors in transplantation. AB - The role of complement in the biology of kidney transplantation is becoming more and more significant, especially but not only because we now have access to drugs inhibiting complement. After describing the main characteristics of complement biology, both activation of the complement cascade and the many regulatory factors, we will review the precise role of complement in kidney transplant biology. Complement activation has been involved in ischemia-reperfusion injury, in the recurrence of several diseases such as atypical hemolytic uremic syndrome, C3 glomerulopathies, and antiphospholipid syndrome, as well as the process of antibody-mediated rejection, either acute or chronic. There are many potentially interesting drugs interfering with complement inhibition that have been or may be studied in kidney transplantation. Currently, the bulk of data concerns eculizumab, a monoclonal antibody blocking the complement cascade at the C5. Its efficacy has been demonstrated in the treatment and prevention of recurrence of atypical hemolytic uremic syndrome with an overall good safety profile. Although it has been reported to be efficacious to prevent antibody-mediated rejection, properly designed trials are currently being performed to state this efficacy. In addition, randomized trials are, in the process, regarding the prevention of ischemia-reperfusion injury after kidney transplantation. PMID- 26376131 TI - Probiotics and chronic kidney disease. AB - Probiotics are the focus of a thorough investigation as a natural biotreatment due to their various health-promoting effects and inherent ability to fight specific diseases including chronic kidney disease (CKD). Indeed, intestinal microbiota has recently emerged as an important player in the progression and complications of CKD. Because many of the multifactorial physiological functions of probiotics are highly strain specific, preselection of appropriate probiotic strains based on their expression of functional biomarkers is critical. The interest in developing new research initiatives on probiotics in CKD have increased over the last decade with the goal of fully exploring their therapeutic potentials. The efficacy of probiotics to decrease uremic toxin production and to improve renal function has been investigated in in vitro models and in various animal and human CKD studies. However to date, the quality of intervention trials investigating this novel CKD therapy is still lacking. This review outlines potential mechanisms of action and efficacy of probiotics as a new CKD management tool, with a particular emphasis on uremic toxin production and inflammation. PMID- 26376133 TI - Do kidney stone formers have a kidney disease? AB - Nephrolithiasis is a highly prevalent disorder affecting approximately one in eleven people and is associated with multiple complications including hypertension, cardiovascular disease, and chronic kidney disease. Significant epidemiologic associations with chronic kidney disease and ESRD have been noted and are reviewed herein, but debate persists in the literature as to whether kidney stone formation is a pathogenic process contributing to kidney disease. Corroborating evidence supporting the presence of kidney disease in stone formers includes the variability of renal function by stone type, the positive association of stone size with renal dysfunction, the presence of markers of renal injury in the urine of even asymptomatic stone formers, and direct evidence of renal tissue injury on histopathology. Proposed pathogenic mechanisms include recurrent obstruction and comorbid conditions such as recurrent urinary tract infections and structural abnormalities. Recent work evaluating the renal histopathology of different groups of stone formers adds further granularity, suggesting variability in mechanisms of renal injury by stone type and confirming the pathogenic effects of crystal formation. Genetic abnormalities leading to stone formation including cystinuria and primary hyperoxaluria, among others, contribute to the burden of disease in the stone-forming population. PMID- 26376136 TI - A Randomized Trial of Phototherapy with Filtered Sunlight in African Neonates. AB - BACKGROUND: Sequelae of severe neonatal hyperbilirubinemia constitute a substantial disease burden in areas where effective conventional phototherapy is unavailable. We previously found that the use of filtered sunlight for the purpose of phototherapy is a safe and efficacious method for reducing total bilirubin. However, its relative safety and efficacy as compared with conventional phototherapy are unknown. METHODS: We conducted a randomized, controlled noninferiority trial in which filtered sunlight was compared with conventional phototherapy for the treatment of hyperbilirubinemia in term and late-preterm neonates in a large, urban Nigerian maternity hospital. The primary end point was efficacy, which was defined as a rate of increase in total serum bilirubin of less than 0.2 mg per deciliter per hour for infants up to 72 hours of age or a decrease in total serum bilirubin for infants older than 72 hours of age who received at least 5 hours of phototherapy; we prespecified a noninferiority margin of 10% for the difference in efficacy rates between groups. The need for an exchange transfusion was a secondary end point. We also assessed safety, which was defined as the absence of the need to withdraw therapy because of hyperthermia, hypothermia, dehydration, or sunburn. RESULTS: We enrolled 447 infants and randomly assigned 224 to filtered sunlight and 223 to conventional phototherapy. Filtered sunlight was efficacious on 93% of treatment days that could be evaluated, as compared with 90% for conventional phototherapy, and had a higher mean level of irradiance (40 vs. 17 MUW per square centimeter per nanometer, P<0.001). Temperatures higher than 38.0 degrees C occurred in 5% of the infants receiving filtered sunlight and in 1% of those receiving conventional phototherapy (P<0.001), but no infant met the criteria for withdrawal from the study for reasons of safety or required an exchange transfusion. CONCLUSIONS: Filtered sunlight was noninferior to conventional phototherapy for the treatment of neonatal hyperbilirubinemia and did not result in any study withdrawals for reasons of safety. (Funded by the Thrasher Research Fund, Salt Lake City, and the National Center for Advancing Translational Sciences of the National Institutes of Health; Clinical Trials.gov number, NCT01434810.). PMID- 26376137 TI - Acute Myeloid Leukemia. PMID- 26376138 TI - IMAGES IN CLINICAL MEDICINE. Ptosis after Swimming in the Red Sea. PMID- 26376139 TI - CASE RECORDS of the MASSACHUSETTS GENERAL HOSPITAL. Case 29-2015. A 38-Year-Old Pregnant Woman with Headache and Visual Symptoms. PMID- 26376140 TI - Out, Out--Making Amyloid's Candle Briefer. PMID- 26376134 TI - New developments in the genetics, pathogenesis, and therapy of IgA nephropathy. AB - Recent years have brought notable progress in the field of IgA nephropathy. Here, we highlight important new directions and latest developments, including successful discovery of several genetic susceptibility loci, formulation of the multihit pathogenesis model, introduction of the Oxford pathology scoring system, and formalization of the Kidney Disease Improving Global Outcomes (KDIGO) consensus treatment guidelines. We focus on the latest genetic findings that confirm a strong contribution of inherited factors and explain some of the geoethnic disparities in disease susceptibility. Most IgA nephropathy susceptibility loci discovered to date encode genes involved in the maintenance of the intestinal epithelial barrier and response to mucosal pathogens. The concerted pattern of interpopulation allelic differentiation across all genetic loci parallels the disease prevalence and correlates with variation in local pathogens, suggesting that multilocus adaptation might have shaped the present day landscape of IgA nephropathy. Importantly, the 'Intestinal Immune Network for IgA Production' emerged as one of the new targets for potential therapeutic intervention. We place these findings in the context of the multihit pathogenesis model and existing knowledge of IgA immunobiology. Lastly, we provide our perspective on the existing treatment options, discuss areas of clinical uncertainty, and outline ongoing clinical trials and translational studies. PMID- 26376141 TI - On Synaptic Circuits, Memory, and Kumquats. PMID- 26376142 TI - Permissive Underfeeding or Standard Enteral Feeding in Critical Illness. PMID- 26376143 TI - Permissive Underfeeding or Standard Enteral Feeding in Critical Illness. PMID- 26376144 TI - Permissive Underfeeding or Standard Enteral Feeding in Critical Illness. PMID- 26376145 TI - Permissive Underfeeding or Standard Enteral Feeding in Critical Illness. PMID- 26376146 TI - Permissive Underfeeding or Standard Enteral Feeding in Critical Illness. PMID- 26376147 TI - Allergen Responses Modified by a GATA3 DNAzyme. PMID- 26376148 TI - Allergen Responses Modified by a GATA3 DNAzyme. PMID- 26376149 TI - Latent Mycobacterium tuberculosis Infection. PMID- 26376150 TI - Latent Mycobacterium tuberculosis Infection. PMID- 26376151 TI - Latent Mycobacterium tuberculosis Infection. PMID- 26376152 TI - Latent Mycobacterium tuberculosis Infection. PMID- 26376153 TI - Latent Mycobacterium tuberculosis Infection. PMID- 26376154 TI - Dactinomycin in NPM1-Mutated Acute Myeloid Leukemia. PMID- 26376155 TI - IMAGES IN CLINICAL MEDICINE. Cutaneous Collagenous Vasculopathy. PMID- 26376156 TI - Effect of posture on forces and moments measured in a Hybrid III ATD lower leg. AB - OBJECTIVE: Anthropomorphic test devices (ATDs) are used to assess real injury risk to occupants of vehicles during injurious events. In the lower leg, values from load cells are compared to injury criteria developed in cadaveric studies. These criteria are typically developed with the leg in a neutral posture, whereas the ATD may assume a wide range of postures during safety evaluation tests. The degree to which the initial posture of an ATD has an effect on the measured forces and moments in the lower leg is unknown. METHODS: A Hybrid III ATD lower leg was impacted in a range of postures under conditions representing a crash test, and peak axial force and adjusted tibia index injury measures were evaluated. Ankle posture was varied in 5 degrees increments using a custom-made footplate, and dorsi/plantarflexion (20 degrees DF to 20 degrees PF) and in/eversion (20 degrees IV to 5 degrees EV) were evaluated. Tibia angle was also varied (representing knee flexion/extension) by +/-10 degrees from neutral. RESULTS: Peak axial force was not affected by ankle flexion or tibia angulation. Adjusted tibia index was lowest for plantarflexion, as well as for tibia angles representative of knee extension. Both peak axial force and adjusted tibia index were lowest for postures of great inversion and were highest in neutral or near neutral postures. CONCLUSIONS: The range of postures tested herein spanned published injury criteria and thus would have made the difference between pass and fail in a safety evaluation. In/eversion had the largest influence on injury metrics, likely due to the change in axial stiffness and altered impact durations in these postures. Results suggest increased injury risk at neutral or near neutral postures, whereas previous cadaveric studies have suggested that in/eversion does not influence injury risk. It is unclear whether the ATD appropriately represents the natural lower leg for impacts in out-of-position testing. Great care must be taken when initially positioning ATDs for safety evaluations, because small perturbations in posture were shown herein to have large effects on the measured injury risk using this tool. PMID- 26376157 TI - Ultraviolet germicidal irradiation susceptibility of methicillin-resistant Staphylococcus aureus compared with methicillin-susceptible S. aureus. AB - Antibiotic misuse and overuse in both the healthcare and agricultural fields have dramatically increased the prevalence of antibiotic resistance in human pathogens. Two strains of methicillin-resistant Staphylococcus aureus (MRSA) (ATCC 43330 and a wild-type) and 1 strain of methicillin-susceptible S. aureus (ATCC 25923) were challenged (9 runs in triplicate) in a preliminary study with ultraviolet germicidal irradiation (UVGI) doses ranging from 0.25 to 3.00 mJ/cm(2). The mean percent kill was calculated for each strain when compared with the control plates (no exposure to UVGI). Then, each strain was challenged (22 runs in triplicate) with UVGI doses of 2.00, 2.50, and 3.00 mJ/cm(2). The results suggest a difference between the doses required to disinfect surfaces with each strain. Assuming a standard error rate of alpha = 0.05, there was a significant difference in variance between the MRSA (ATCC 43330 and wild type) strains and the S. aureus (ATCC 25923) methicillin-susceptible strain. PMID- 26376158 TI - Poly-victimization and mental health of street children in Lahore city. AB - BACKGROUND: Street children are vulnerable to a number of problems throughout their lives. Poly-victimization covers the different domains of the difficulties they face on streets, it is also notable to find out the impact of poly victimization on the mental health of street children. AIMS: The purpose of the study was to examine the relationship between poly-victimization and mental health in street children of Lahore city. It was hypothesized that there is likely to be a predictive relationship between poly-victimization and mental health of street children. METHODS: Through purposive sampling a sample of 77 street boys was collected from Lahore city, with the help of three government and private organizations working with street children. Sample included only boys within the age range of 9-13 years (M = 10.66, SD = 1.26) who have been residing on streets for more than one month. Juvenile Victimization Questionnaire and Mental Health Inventory were used for assessment of poly-victimization and mental health respectively. RESULTS: The results indicated that poly victimization positively predicted the psychological distress and negatively predicted psychological wellbeing in street children. CONCLUSION: The most common type of victimization was conventional crime which negatively predicts mental health of street children. The results have important implications for the policy makers to develop improved services for this vulnerable group. PMID- 26376159 TI - Gastric Burkitt Lymphoma in a Teenager. PMID- 26376160 TI - Handcrafted cuff manometers do not accurately measure endotracheal tube cuff pressure. AB - OBJECTIVE: To test the agreement between two handcrafted devices and a cuff specific manometer. METHODS: The agreement between two handcrafted devices adapted to measure tracheal tube cuff pressure and a cuff-specific manometer was tested on 79 subjects. The cuff pressure was measured with a commercial manometer and with two handcrafted devices (HD) assembled with aneroid sphygmomanometers (HD1 and HD2). The data were compared using Wilcoxon and Spearman tests, the intraclass correlation coefficient (ICC) and limit-of-agreement analysis. RESULTS: Cuff pressures assessed with handcrafted devices were significantly different from commercial device measurements (pressures were higher when measured with HD1 and lower with HD2). The ICCs between the commercial device and HD1 and HD2 were excellent (ICC = 0.8 p < 0.001) and good (ICC = 0.66, p < 0.001), respectively. However, the Bland- Altman plots showed wide limits of agreement between HD1 and HD2 and the commercial device. CONCLUSION: The handcrafted manometers do not provide accurate cuff pressure measurements when compared to a cuff-specific device and should not be used to replace the commercial cuff manometers in mechanically ventilated patients. PMID- 26376161 TI - A guided approach to diagnose severe muscle weakness in the intensive care unit. PMID- 26376162 TI - PIRO and sepsis stratification: reality or a mirage? PMID- 26376163 TI - Specificity of vascular endothelial growth factor treatment for radiation necrosis. AB - Recently, radiation induced necrosis in the brain has been treated using bevacizumab, an anti-VEGF antibody. We validated the VEGF specificity by comparing the therapeutic efficacy of anti-VEGF with non-specific isotype control antibody. Additionally, we found that VEGF over-expression and RN developed simultaneously, which precludes preventative anti-VEGF treatment. PMID- 26376164 TI - A Bayesian Model to Describe Factors Influencing Trough Levels of Vancomycin in Hemodialysis Patients. AB - BACKGROUND/AIMS: In hemodialysis patients, there is a marked inter-individual variability in the pharmacokinetics of vancomycin. This retrospective study was carried out to design a model describing the parameters that may influence the trough concentrations of vancomycin (TCV) in hemodialysis patients. METHODS: A Bayesian model was constructed from data obtained during 314 hemodialysis sessions performed in 31 hemodialysis patients receiving vancomycin. The model's validity was assessed by goodness of fit. A bootstrap resampling method was used to calculate bias and accuracy for 80 predicted and observed TCV. RESULTS: A total of 31 patients underwent dialysis 3 times a week for a mean duration of 4 h. Their mean age was 69 +/- 12 years. The vancomycin infusion was started 30 min before the scheduled end of the dialysis session at a flow rate of 1,000 mg/h. The mean TCV of the study population was 16.1 +/- 3.2 mg/l. The area under receiver operating characteristic curve of the constructed model was 95.2%. In the validation sample (80 randomly selected TCV), the observed mean TCV was 15.8 +/- 3.6 mg/l, whereas the mean TCV predicted by the model was 15.7 +/- 3.0 mg/l. If the mean bias was low between the predicted and observed TCV (-0.1 mg/l), SD was high (3.43 mg/l). The variables most closely linked to TCV were in descending order: weight after dialysis, weight before dialysis, the dose of vancomycin administered during the previous dialysis session and creatinine concentration before dialysis. CONCLUSION: This simple model describes patient-related and dialysis-related parameters that mainly influence TCV. Before its use in clinical practice, this model should be validated prospectively. PMID- 26376165 TI - Bone marrow spontaneous lesions in rodents from nonclinical 104-week carcinogenicity studies. AB - The authors performed a retrospective study to determine the incidences and range of spontaneous lesions in the bone marrow (sternum and femur) of control mice and rats. Data was collected from 2186 mice (Crl:CD-1(ICR)BR), and 2347 rats (Han Wistar and CD(SD) rats) from the control dose groups of 104-week carcinogenicity studies carried out between 2005 and 2014. The incidence of spontaneous lesions in the bone marrow was higher in mice than in rats, and in both species non neoplastic lesions were more common than neoplastic lesions. In mice, the most common non-neoplastic lesions in the bone marrow were increased cellularity, pigmented macrophages, and decreased cellularity, and the most common neoplastic lesions were malignant lymphoma, granulocytic leukemia and histiocytic sarcoma. There were occasional sex and site differences (sternum marrow vs femur marrow) in the incidence of a few bone marrow lesions in mice. In rats, the most common non-neoplastic lesions were increased cellularity and stromal fibrosis, and the most common neoplastic lesion was malignant lymphoma. In rats, no sex predilection in the incidence of bone marrow lesions was apparent, and there were no significant site differences in the incidence of lesions. To the best knowledge of the authors, there are no recent reports on spontaneous pathological findings in bone marrow of rodents, and we believe that these results will facilitate the interpretation of background findings and/or their increased incidence in carcinogenicity studies. PMID- 26376166 TI - Education and Mortality in the Rome Longitudinal Study. AB - BACKGROUND: A large body of evidence supports an inverse association between socioeconomic status and mortality. We analysed data from a large cohort of residents in Rome followed-up between 2001 and 2012 to assess the relationship between individual education and mortality. We distinguished five causes of death and investigated the role of age, gender, and birthplace. METHODS: From the Municipal Register we enrolled residents of Rome on October 21st 2001 and collected information on educational level attained from the 2001 Census. We selected Italian citizens aged 30-74 years and followed-up their vital status until 2012 (n = 1,283,767), identifying the cause of death from the Regional Mortality Registry. We calculated hazard ratios (HRs) for overall and cause specific mortality in relation to education. We used age, gender, and birthplace for adjusted or stratified analyses. We used the inverse probability weighting approach to account for right censoring due to emigration. RESULTS: We observed an inverse association between education (none vs. post-secondary+ level) and overall mortality (HRs(95%CIs): 2.1(1.98-2.17), males; 1.5(1.46-1.59), females) varying according to demographic characteristics. Cause-specific analysis also indicated an inverse association with education, in particular for respiratory, digestive or circulatory system related-mortality, and the youngest people seemed to be more vulnerable to low education. CONCLUSION: Our results confirm the inverse association between education and overall or cause-specific mortality and show differentials particularly marked among young people compared to the elderly. The findings provide further evidence from the Mediterranean area, and may contribute to national and cross-country comparisons in Europe to understand the mechanisms generating socioeconomic differentials especially during the current recession period. PMID- 26376167 TI - Localisation of RNAs and proteins in nucleolar precursor bodies of early mouse embryos. AB - Early embryos of all mammalian species contain morphologically distinct but transcriptionally silent nucleoli called the nucleolar precursor bodies (NPBs), which, unlike normal nucleoli, have been poorly studied at the biochemical level. To bridge this gap, here we examined the occurrence of RNA and proteins in early mouse embryos with two fluorochromes - an RNA-binding dye pyronin Y (PY) and the protein-binding dye fluorescein-5'-isothiocyanate (FITC). The staining patterns of zygotic NPBs were then compared with those of nucleolus-like bodies (NLBs) in fully grown surrounded nucleolus (SN)-type oocytes, which are morphologically similar to NPBs. We show that both entities contain proteins, but unlike NLBs, NPBs are significantly impoverished for RNA. Detectable amounts of RNA appear on the NPB surface only after resumption of rDNA transcription and includes pre rRNAs and 28S rRNA as evidenced by fluorescence in situ hybridisation with specific oligonucleotide probes. Immunocytochemical assays demonstrate that zygotic NPBs contain rRNA processing factors fibrillarin, nucleophosmin and nucleolin, while UBF (the RNA polymerase I transcription factor) and ribosomal proteins RPL26 and RPS10 are not detectable. Based on the results obtained and data in the contemporary literature, we suggest a scheme of NPB assembly and maturation to normal nucleoli that assumes utilisation of maternally derived nucleolar proteins but of nascent rRNAs. PMID- 26376168 TI - Rapid next-generation sequencing of dengue, EV-A71 and RSV-A viruses. AB - Accurate characterisation of viral strains constitutes a crucial objective for the management of modern virus collections. Next-generation sequencing (NGS) provides technical solution for fast and cost-effective full genome sequencing. Here, we report protocols for rapid full-genome characterisation of RNA viruses of medical importance: dengue virus, enterovirus A71 and respiratory syncytial virus A, based on a specific amplification step followed by NGS-sequencing. A subset of full-length genome sequences representing the genetic diversity of each virus type was selected in GenBank and used to design primer sets allowing the amplification of the complete genome in 3-8 overlapping PCR fragments. The technique was used for characterising 53 strains (33 DENV, 8 EV-A71, 12 RSV-A) from various genotypes and origins. In a single assay, and in just 4 days, it provided for all strains an excellent genomic coverage (~ 99% including complete ORF for all strains) and accurate sequences with high number of reads per position (250-3500 on average). The elaboration of specific PCR-based full-genome sequencing protocols for diverse virus groups is likely to revolutionise the characterisation of viral isolates in modern collection, but also to contribute in the next future to the study of RNA viruses directly from biological samples. PMID- 26376169 TI - Congenital factor V and VIII deficiency in women: a systematic review of literature and report of two new cases. AB - Factor V and factor VIII deficiency (F5F8D) is a rare congenital bleeding disorder. There is a paucity of data in the literature about obstetric and gynaecological problems in women affected by F5F8D. The aim of this review was to examine obstetric complications and gynaecological problems in women with congenital F5F8D and present two new cases. An electronic search was performed to identify the published literature on PUBMED, MEDLINE and EMBASE databases using the following keywords 'congenital factor V and factor VIII deficiency' and 'women or pregnancy'. A total of 23 relevant articles were found and included in this systematic review: 15 case reports and 10 case series dating from 1976 to 2015. A total number of 86 women were identified. Heavy menstrual bleeding was the most common bleeding symptom in women (49%). Recurrent ovulation bleeding and haemorrhagic ovarian cyst were reported in three women. Nineteen pregnancies were reported (including our two case reports). There were no miscarriages. Postpartum bleeding occurred in six (32%) deliveries. In conclusion, data are very limited on gynaecological and obstetric problems in women with F5F8D. Heavy menstrual bleeding is a common problem. There is also an increased risk of postpartum haemorrhage. Close collaboration between haemophilia, obstetric and gynaecological teams is important to prevent and manage obstetric and gynaecological bleeding complications. PMID- 26376170 TI - Computed Tomography and Magnetic Resonance Imaging in the Differentiation of Osteoporotic Fractures From Neoplastic Metastatic Fractures. AB - Determining whether a low-intensity vertebral fracture in an older person, particularly one with a history of cancer, is due to osteoporosis (OP) or is the result of a metastasis, is a not infrequent clinical problem that has important prognostic and therapeutic implications. The 2 types of fracture are usually indistinguishable on plain radiographs and require higher order imaging for diagnosis. Magnetic resonance imaging is the modality of choice because of its unique ability to depict the bone marrow, which becomes transiently edematous in an acute OP fracture. Preservation of at least part of the normal marrow signal, the visualization of a fracture line parallel to the end plates, the presence of an intravertebral cleft, lack of pedicle involvement, and no extra-osseous mass all favor a benign OP fracture. Absence of the preceding signs, particularly if there is complete replacement of the normal bone marrow and a convex posterior contour of the vertebral body, favors a fracture of malignant origin. Non-routine magnetic resonance sequences using diffusion-weighted imaging and/or chemical shift imaging may be helpful in difficult cases. PMID- 26376171 TI - Osteoporotic Vertebral Fractures as Part of Systemic Disease. AB - Our understanding of the genetic control of skeletogenesis and bone remodeling is expanding, and normally, bone resorption and bone formation are well balanced through regulation by hormones, growth factors, and cytokines. Osteoporosis is considered a systemic disease characterized by low bone mass and microarchitectural deterioration of bone tissue. Consequent increased bone fragility results in higher fracture risk. The most common osteoporotic fractures are located in the spine, and they form a significant health issue. A large variety of systemic diseases are associated with risk of osteoporotic vertebral fractures, illustrating its multifactorial etiology. Prevalences of these conditions vary from common to extremely rare, and incidence peaks differ according to etiology. This review appreciates different aspects of osteoporotic vertebral fractures as part of systemic disease, including genetic, immunologic, inflammatory, metabolic, and endocrine pathways. It seems impossible to be all comprehensive on this topic; nevertheless, we hope to provide a reasonably thorough overview. Plenty remains to be elucidated in this field, identifying even more associated diseases and further exposing pathophysiological mechanisms underlying osteoporotic vertebral fractures. PMID- 26376172 TI - Genetics of Osteoporotic Vertebral Fractures. AB - Our understanding of the genetic control of skeletogenesis and bone remodeling is increasing, and in addition to various nongenetic risk factors, a positive family history confers an increased risk of fracture. Vertebral fractures are the most common osteoporotic fractures and they are often a first manifestation of osteoporosis. This review presents the current state of knowledge on the genetic basis of osteoporotic vertebral fractures and, additionally, of structural vertebral deformities resembling osteoporotic vertebral fractures but which may have their own genetic basis. We conclude that, apart from tentative screening for rare monogenic forms of osteoporosis in very unusual case presentations, not enough is currently known to encourage routine genetic screening in regular osteoporotic vertebral fracture cases. PMID- 26376173 TI - An Aryne-Based Route to Substituted Benzoisothiazoles. AB - The combination of arynes, generated using fluoride from the corresponding 2 (trimethylsilyl)aryl triflates, and 3-hydroxy-4-aminothiadiazoles leads to the selective formation of 3-amino-substituted benzo[d]isothiazoles. Variation of the substitution pattern of the aryne precursor, and of the thiadiazole, is possible, with the target heterocycles being obtained in good to excellent yields. In all cases, use of 3-hydroxy-4-aminothiadiazoles leads to incorporation of the amino substituent in the product heterocycle. PMID- 26376174 TI - Is Having Clonal Cytogenetic Abnormalities the Same as Having Leukaemia. AB - A finding of cytogenetic abnormalities, even when these are clonal and even when the abnormalities are typically associated with leukaemia, is not the same as a person having leukaemia. We describe a person who had acute myeloid leukaemia (AML) and achieved a complete haematological remission and who then had persistent and transient clonal cytogenetic abnormalities for 22 years but no recurrence of leukaemia. These data suggest that clones of myeloid cells with mutations and capable of expanding to levels detectable by routine cytogenetic analyses do not all eventuate in leukaemia, even after a prolonged observation interval. The possibility of incorrectly diagnosing a person as having leukaemia becomes even greater when employing more sensitive techniques to detect mutations such as by polymerase chain reaction and whole-exome or whole-genome sequencing. Caution is needed when interpreting clonal abnormalities in AML patients with normal blood and bone marrow parameters. PMID- 26376175 TI - Opportunities for improving animal welfare in rodent models of epilepsy and seizures. AB - Animal models of epilepsy and seizures, mostly involving mice and rats, are used to understand the pathophysiology of the different forms of epilepsy and their comorbidities, to identify biomarkers, and to discover new antiepileptic drugs and treatments for comorbidities. Such models represent an important area for application of the 3Rs (replacement, reduction and refinement of animal use). This report provides background information and recommendations aimed at minimising pain, suffering and distress in rodent models of epilepsy and seizures in order to improve animal welfare and optimise the quality of studies in this area. The report includes practical guidance on principles of choosing a model, induction procedures, in vivo recordings, perioperative care, welfare assessment, humane endpoints, social housing, environmental enrichment, reporting of studies and data sharing. In addition, some model-specific welfare considerations are discussed, and data gaps and areas for further research are identified. The guidance is based upon a systematic review of the scientific literature, survey of the international epilepsy research community, consultation with veterinarians and animal care and welfare officers, and the expert opinion and practical experience of the members of a Working Group convened by the United Kingdom's National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs). PMID- 26376176 TI - One size does not fit all: Examining heterogeneity and identifying moderators of the alliance-outcome association. AB - Although the alliance-outcome association is one of the most consistent findings in psychotherapy research, it is also highly heterogeneous. Little is known about the factors explaining this variability, and consequently there is a lack of adequate knowledge about how to utilize this association to improve treatment. The present study had the following objectives: (a) to examine the associations between within- and between-individual variability in alliance and outcome, controlling for previous symptomatic levels; (b) to examine the duration of the alliance-outcome association; and (c) to examine potential moderators of the alliance-outcome association. A total of 547 patients treated in a primary care psychotherapy setting in Chile were randomly assigned to 5 feedback conditions. The alliance-outcome association was analyzed using multilevel models, disentangling changes in alliance within-individuals from alliance between individuals. Patient and therapist characteristics were examined as potential moderators. Findings suggest that patients who reported a better early alliance also reported a better outcome. Furthermore, patients reporting time-specific improvement in alliance also reported a greater reduction in symptoms. The unique effect of alliance on outcome at one point in time is maintained for a period of 2 weeks. Patients with more severe symptoms and longer treatments benefited more from a good alliance. Therapists identifying themselves as more integrative in their treatment orientation were able to better utilize good alliances for treatment success. Finally, the size of the alliance-outcome association can be manipulated by feedback to therapists. PMID- 26376177 TI - Bullying prevention in schools by targeting cognitions, emotions, and behavior: Evaluating the effectiveness of the REBE-ViSC program. AB - The effectiveness of a class-based antibullying prevention program on cognitions, emotions, and behaviors was investigated. The program consists of a cognitive behavioral (Rational Emotive Behavioral Education; REBE) and a behavioral (Viennese Social Competence; ViSC) component. The REBE program is based on rational emotive behavioral theory and contains 9 student lessons. The ViSC program is based on social learning theory and comprises 10 student lessons. The order of the programs was experimentally manipulated. The REBE-ViSC program was implemented in 5 schools (14 classes), the ViSC-REBE program was implemented in 3 schools (9 classes), and 3 schools (11 classes) served as an untreated control group. Data were collected during 1 school year at pretest, midpoint, and posttest. Emotions (overt and internalizing anger), cognitions (learning and entitlement), and behaviors (bullying perpetration and bullying victimization) were measured with self-assessments. To examine the effectiveness of the REBE ViSC/ViSC-REBE program, multilevel growth models were applied (time points at Level 1, individuals at Level 2, and classes at Level 3). The analyses revealed that the program effects differed depending on the order of the programs. The REBE-ViSC condition was more effective in changing negative emotions than the ViSC-REBE condition; both experimental conditions were effective in reducing dysfunctional cognitions, whereas no behavioral change was found in the 2 experimental groups when compared with the control group. To improve program effectiveness regarding behavioral changes, a multilevel whole-school approach including a teacher component is recommended. PMID- 26376178 TI - Linkages between mental health need and help-seeking behavior among adolescents: Moderating role of ethnicity and cultural values. AB - Risk of developing emotional and behavioral mental health problems increases markedly during adolescence. Despite this increasing need, most adolescents, particularly ethnic minority youth, do not seek professional help. Informed by conceptual models of health behavior, the current study examined how cultural values are related to help seeking among adolescents from 2 distinct racial/ethnic groups. Using a prospective survey design, 169 Vietnamese American and European American youth in 10th and 11th grade reported on their mental health need, as measured by emotional/behavioral mental health symptoms and stressful life events, with participants reporting on their help-seeking behavior at 6-month follow-up assessments. Multinomial logistic regression analyses indicated that mental health need interacted with cultural values and ethnicity to predict help-seeking behavior. Specifically, associations between symptoms and stressful life events, and help-seeking behavior were smaller among Vietnamese American adolescents, and among adolescents with strong family obligation values. These results underscore the complex sociocultural factors influencing adolescents' help-seeking behavior, which have important implications for engaging youth in needed mental health care. PMID- 26376179 TI - Improved Framework for Tractography Reconstruction of the Optic Radiation. AB - The optic radiation (OR) is one of the major components of the visual system and a key structure at risk in white matter diseases such as multiple sclerosis (MS). However, it is challenging to perform track reconstruction of the OR using diffusion MRI due to a sharp change of direction in the Meyer's loop and the presence of kissing and crossing fibers along the pathway. As such, we aimed to provide a highly precise and reproducible framework for tracking the OR from thalamic and visual cortex masks. The framework combined the generation of probabilistic streamlines by high order fiber orientation distributions estimated with constrained spherical deconvolution and an automatic post-processing based on anatomical exclusion criteria (AEC) to compensate for the presence of anatomically implausible streamlines. Specifically, those ending in the contralateral hemisphere, cerebrospinal fluid or grey matter outside the visual cortex were automatically excluded. We applied the framework to two distinct high angular resolution diffusion-weighted imaging (HARDI) acquisition protocols on one cohort, comprised of ten healthy volunteers and five MS patients. The OR was successfully delineated in both HARDI acquisitions in the healthy volunteers and MS patients. Quantitative evaluation of the OR position was done by comparing the results with histological reference data. Compared with histological mask, the OR reconstruction into a template (OR-TCT) was highly precise (percentage of voxels within the OR-TCT correctly defined as OR), ranging from 0.71 to 0.83. The sensitivity (percentage of voxels in histological reference mask correctly defined as OR in OR-TCT) ranged from 0.65 to 0.81 and the accuracy (measured by F1 score) was 0.73 to 0.77 in healthy volunteers. When AEC was not applied the precision and accuracy decreased. The absolute agreement between both HARDI datasets measured by the intraclass correlation coefficient was 0.73. This improved framework allowed us to reconstruct the OR with high reliability and accuracy independently of the acquisition parameters. Moreover, the reconstruction was possible even in the presence of tissue damage due to MS. This framework could also be applied to other tracts with complex configuration. PMID- 26376180 TI - Altered Functional Connectivity in Patients with Subcortical Vascular Cognitive Impairment--A Resting-State Functional Magnetic Resonance Imaging Study. AB - Recent neuroimaging studies have shown that people with subcortical vascular cognitive impairment (sVCI) have structural and functional abnormalities in the frontal lobe and subcortical brain sites. In this study, we used seed-based resting-state functional connectivity (rsFC) analysis and voxel-mirrored homotopic connectivity (VMHC) techniques to investigate the alteration of rsFC in patients with sVCI. rsFC and structural magnetic resonance images were acquired for 51 patients with subcortical cerebrovascular disease. All patients were subdivided based on cognitive status into 29 with sVCI and 22 controls; patient characteristics were matched. rsFC of the posterior cingulate cortex (PCC) and VMHC were calculated separately, and rsFC of the PCC and VMHC between the two groups were compared. The regions showing abnormal rsFC of the PCC or VMHC in sVCI patients were adopted as regions of interest for correlation analyses. Our results are as follows: The patients with sVCI exhibited increases in rsFC in the left middle temporal lobe, right inferior temporal lobe and left superior frontal gyrus, and significant decreases in rsFC of the left thalamus with the PCC. sVCI patients showed a significant deficit in VMHC between the bilateral lingual gyrus, putamen, and precentral gyrus. Additionally, the z-memory score was significantly positively associated with connectivity between the left thalamus and the PCC (r = 0.41, p = 0.03, uncorrected) in the sVCI group. Our findings suggest that the frontal lobe and subcortical brain sites play an important role in the pathogenesis of sVCI. Furthermore, rsFC between the left thalamus and the PCC might indicate the severity of sVCI. PMID- 26376181 TI - Patient-individualized CD8+ cytolytic T-cell therapy effectively combats minimal residual leukemia in immunodeficient mice. AB - Adoptive transfer of donor-derived cytolytic T-lymphocytes (CTL) has evolved as a promising strategy to improve graft-versus-leukemia (GvL) effects in allogeneic hematopoietic stem-cell transplantation. However, durable clinical responses are often hampered by limited capability of transferred T cells to establish effective and sustained antitumor immunity in vivo. We therefore analyzed GvL responses of acute myeloid leukemia (AML)-reactive CD8(+) CTL with central and effector memory phenotype in a new allogeneic donor-patient specific humanized mouse model. CTL lines and clones obtained upon stimulation of naive CD45RA(+) donor CD8(+) T cells with either single HLA antigen-mismatched or HLA-matched primary AML blasts, respectively, elicited strong leukemia reactivity during cytokine-optimized short to intermediate (i.e., 2-8 weeks) culture periods. Single doses of CTL were intravenously infused into NOD/scidIL2Rcg(null) mice when engraftment with patient AML reached bone marrow infiltration of 1-5%, clinically defining minimal residual disease status. This treatment resulted in complete regression of HLA-mismatched and strong reduction of HLA-matched AML infiltration, respectively. Most importantly, mice receiving AML-reactive CTL showed significantly prolonged survival. Transferred CTL were detectable in murine bone marrow and spleen and demonstrated sustained AML-reactivity ex vivo. Moreover, injections with human IL-15 clearly promoted CTL persistence. In summary, we show that naive donor-derived CD8(+) CTL effectively combat patient AML blasts in immunodeficient mice. The donor-patient specific humanized mouse model appears suitable to evaluate therapeutic efficacy of AML-reactive CTL before adoptive transfer into patients. It may further help to identify powerful leukemia rejection antigens and T-cell receptors for redirecting immunity to leukemias even in a patient-individualized manner. PMID- 26376183 TI - Readability and Content Assessment of Informed Consent Forms for Medical Procedures in Croatia. AB - BACKGROUND: High quality of informed consent form is essential for adequate information transfer between physicians and patients. Current status of medical procedure consent forms in clinical practice in Croatia specifically in terms of the readability and the content is unknown. The aim of this study was to assess the readability and the content of informed consent forms for diagnostic and therapeutic procedures used with patients in Croatia. METHODS: 52 informed consent forms from six Croatian hospitals on the secondary and tertiary health care level were tested for reading difficulty using Simple Measure of Gobbledygook (SMOG) formula adjusted for Croatian language and for qualitative analysis of the content. RESULTS: The averaged SMOG grade of analyzed informed consent forms was 13.25 (SD 1.59, range 10-19). Content analysis revealed that informed consent forms included description of risks in 96% of the cases, benefits in 81%, description of procedures in 78%, alternatives in 52%, risks and benefits of alternatives in 17% and risks and benefits of not receiving treatment or undergoing procedures in 13%. CONCLUSIONS: Readability of evaluated informed consent forms is not appropriate for the general population in Croatia. The content of the forms failed to include in high proportion of the cases description of alternatives, risks and benefits of alternatives, as well as risks and benefits of not receiving treatments or undergoing procedures. Data obtained from this research could help in development and improvement of informed consent forms in Croatia especially now when Croatian hospitals are undergoing the process of accreditation. PMID- 26376184 TI - Correction: Gene Expression Profiling of Development and Anthocyanin Accumulation in Kiwifruit (Actinidia chinensis) Based on Transcriptome Sequencing. PMID- 26376182 TI - Detection and Validation of QTL Affecting Bacterial Cold Water Disease Resistance in Rainbow Trout Using Restriction-Site Associated DNA Sequencing. AB - Bacterial cold water disease (BCWD) causes significant economic loss in salmonid aquaculture. Using microsatellite markers in a genome scan, we previously detected significant and suggestive QTL affecting phenotypic variation in survival following challenge with Flavobacterium psychrophilum, the causative agent of BCWD in rainbow trout. In this study, we performed selective genotyping of SNPs from restriction-site associated DNA (RAD) sequence data from two pedigreed families (2009070 and 2009196) to validate the major QTL from the previous work and to detect new QTL. The use of RAD SNPs in the genome scans increased the number of mapped markers from ~300 to ~5,000 per family. The significant QTL detected in the microsatellites scan on chromosome Omy8 in family 2009070 was validated explaining up to 58% of the phenotypic variance in that family, and in addition, a second QTL was also detected on Omy8. Two novel QTL on Omy11 and 14 were also detected, and the previously suggestive QTL on Omy1, 7 and 25 were also validated in family 2009070. In family 2009196, the microsatellite significant QTL on Omy6 and 12 were validated and a new QTL on Omy8 was detected, but none of the previously detected suggestive QTL were validated. The two Omy8 QTL from family 2009070 and the Omy12 QTL from family 2009196 were found to be co localized with handling and confinement stress response QTL that our group has previously identified in a separate pedigreed family. With the currently available data we cannot determine if the co-localized QTL are the result of genes with pleiotropic effects or a mere physical proximity on the same chromosome segment. The genetic markers linked to BCWD resistance QTL were used to query the scaffolds of the rainbow trout reference genome assembly and the QTL positive scaffold sequences were found to include 100 positional candidate genes. Several of the candidate genes located on or near the two Omy8 QTL detected in family 2009070 suggest potential linkages between stress response and the regulation of immune response in rainbow trout. PMID- 26376186 TI - Genuflecting to Hospital Variation in Home Discharge. PMID- 26376185 TI - In Situ Characterization of Splenic Brucella melitensis Reservoir Cells during the Chronic Phase of Infection in Susceptible Mice. AB - Brucella are facultative intracellular Gram-negative coccobacilli that chronically infect humans as well as domestic and wild-type mammals, and cause brucellosis. Alternatively activated macrophages (M2a) induced by IL-4/IL-13 via STAT6 signaling pathways have been frequently described as a favorable niche for long-term persistence of intracellular pathogens. Based on the observation that M2a-like macrophages are induced in the spleen during the chronic phase of B. abortus infection in mice and are strongly infected in vitro, it has been suggested that M2a macrophages could be a potential in vivo niche for Brucella. In order to test this hypothesis, we used a model in which infected cells can be observed directly in situ and where the differentiation of M2a macrophages is favored by the absence of an IL-12-dependent Th1 response. We performed an in situ analysis by fluorescent microscopy of the phenotype of B. melitensis infected spleen cells from intranasally infected IL-12p40-/- BALB/c mice and the impact of STAT6 deficiency on this phenotype. Most of the infected spleen cells contained high levels of lipids and expressed CD11c and CD205 dendritic cell markers and Arginase1, but were negative for the M2a markers Fizz1 or CD301. Furthermore, STAT6 deficiency had no effect on bacterial growth or the reservoir cell phenotype in vivo, leading us to conclude that, in our model, the infected cells were not Th2-induced M2a macrophages. This characterization of B. melitensis reservoir cells could provide a better understanding of Brucella persistence in the host and lead to the design of more efficient therapeutic strategies. PMID- 26376187 TI - Use of antibiotics by urban and rural residents in Heilongjiang Province, China: cross-sectional study. AB - OBJECTIVE: To identify and compare the factors affecting the knowledge of, attitude towards and use of antibiotics between urban and rural residents in China. METHODS: A total of 3631 urban and rural residents in Heilongjiang Province, China, were selected using random sampling. Questionnaires recorded demographic characteristics and participant knowledge of, attitude towards and use of antibiotics. The responses of rural and urban residents were compared, and logistic regression analysis was applied to identify the factors that may contribute to the knowledge of, attitude towards and use of antibiotics. RESULTS: The majority of the participants (>60%) were aware that antibiotics could be used to treat bacterial infections and that bacteria could be resistant to antibiotics. However, only roughly half (40-60%) of the participants were aware that bacterial resistance to antibiotics had become a problem in China. Urban participants reported a more adequate knowledge of, attitude towards and use of antibiotics than rural participants. Logistic regression analysis indicated that urban residency, female gender and level of education were associated with knowledge of, attitude towards and use of antibiotics. CONCLUSIONS: Within our sample in Heilongjiang Province, the knowledge of, attitude towards and use of antibiotics were suboptimal in roughly half of all urban and rural residents, but better in urban than in rural residents. Targeted interventions to educate rural residents in particular may reduce the misuse of antibiotics. PMID- 26376188 TI - A Patient with Kawasaki Disease Following Influenza Vaccinations. PMID- 26376189 TI - Features of Septic Shock and Hepatitis in Parechovirus Myocarditis. PMID- 26376190 TI - In Reply: Features of Septic Shock and Hepatitis in Parechovirus Myocarditis. PMID- 26376191 TI - Resistance of Bacterial Isolates from Neonates with Suspected Sepsis to Recommended First-Line Antibiotics in Fiji. PMID- 26376194 TI - (1,2-Diaminoethane-1,2-diyl)bis(N-methylpyridinium) Salts as a Prospective Platform for Designing Recyclable Prolinamide-Based Organocatalysts. AB - A new efficient and highly recyclable organocatalyst has been developed for asymmetric cross-aldol reactions under neat conditions in ketone-ketone, ketone aldehyde, and aldehyde-aldehyde systems. The catalyst features two prolinamide fragments and a C2-symmetrical (1,2-diaminoethane-1,2-diyl)bis(N methylpyridinium) group. The catalyst retained high activity and excellent stereoselection over the operating period of more than 830 h (25 cycles). An ab initio theoretical investigation explained the absolute configuration of the products and different stereoinduction levels for designed diastereomeric organocatalysts. PMID- 26376193 TI - Energy Expenditure and Metabolic Changes of Free-Flying Migrating Northern Bald Ibis. AB - Many migrating birds undertake extraordinary long flights. How birds are able to perform such endurance flights of over 100-hour durations is still poorly understood. We examined energy expenditure and physiological changes in Northern Bald Ibis Geronticus eremite during natural flights using birds trained to follow an ultra-light aircraft. Because these birds were tame, with foster parents, we were able to bleed them immediately prior to and after each flight. Flight duration was experimentally designed ranging between one and almost four hours continuous flights. Energy expenditure during flight was estimated using doubly labelled-water while physiological properties were assessed through blood chemistry including plasma metabolites, enzymes, electrolytes, blood gases, and reactive oxygen compounds. Instantaneous energy expenditure decreased with flight duration, and the birds appeared to balance aerobic and anaerobic metabolism, using fat, carbohydrate and protein as fuel. This made flight both economic and tolerable. The observed effects resemble classical exercise adaptations that can limit duration of exercise while reducing energetic output. There were also in flight benefits that enable power output variation from cruising to manoeuvring. These adaptations share characteristics with physiological processes that have facilitated other athletic feats in nature and might enable the extraordinary long flights of migratory birds as well. PMID- 26376195 TI - Modeling the CH Stretch Vibrational Spectroscopy of M(+)[Cyclohexane] (M = Li, Na, and K) Ions. AB - The CH stretch vibrations of M(+)[cyclohexane][Ar] (M = Li, Na, and K) cluster ions were theoretically modeled. Results were compared to the corresponding infrared photodissociation spectra of Patwari and Lisy [ J. Chem. Phys A 2007 , 111 , 7585 ]. The experimental spectra feature a substantial spread in CH stretch vibration frequencies due to the alkali metal cation binding to select hydrogens of cyclohexane. This spread was observed to increase with decreasing metal ion size. Exploring the potential energy landscape revealed the presence of three conformers whose energy minima lie within ~1 kcal of each other. It was determined that in all conformers the metal ion interacts with three hydrogen atoms; these hydrogen atoms can be either equatorial or axial. The corresponding spectra for these conformers were obtained with a theoretical model Hamiltonian [ J. Chem. Phys. 2013 , 138 , 064308 ] that consists of local mode CH stretches bilinearly coupled to each other and Fermi coupled to lower frequency modes. Frequencies and coupling parameters were obtained from electronic structure calculations that were subsequently scaled on the basis of previous studies. Theoretical spectra of a single low energy conformer were found to match well with the experimental spectra. The relative frequency shifts with changing metal ion size were accurately modeled with parameters generated by using omegaB97X-D/6 311++(2d,p) calculations. PMID- 26376196 TI - E-cigarettes: promise or peril? PMID- 26376197 TI - The Usefulness and Feasibility of Mobile Interface in Tuberculosis Notification (MITUN) Voice Based System for Notification of Tuberculosis by Private Medical Practitioners--A Pilot Project. AB - INTRODUCTION: Tuberculosis (TB) is a notifiable disease and health care providers are required to notify every TB case to local authorities. We conducted a pilot study to determine the usefulness and feasibility of mobile interface in TB notification (MITUN) voice based system for notification of TB cases by private medical practitioners. METHODOLOGY: The study was conducted during September 2013 to October 2014 in three zones of Chennai, an urban setting in South India. Private clinics wherein services are provided by single private medical practitioners were approached. The steps involved in MITUN included: Registration of the practitioners and notification of TB cases by them through voice interactions. Pre and post-intervention questionnaires were administered to collect information on TB notification practices and feasibility of MITUN after an implementation period of 6 months. RESULTS: A total of 266 private medical practitioners were approached for the study. Of them, 184 (69%) participated in the study; of whom 11 (6%) practitioners used MITUN for TB notification. Reasons for not using MITUN include lack of time, referral of patients to government facility, issues related to patient confidentiality and technical problems. Suggestions for making mobile phone based TB notification process user-friendly included reducing call duration, including only crucial questions and using missed call or SMS options. CONCLUSION: The performance (feasibility and usefulness) of MITUN voice based system for TB notification in the present format was sub-optimal. Perceived problems, logistical and practical issues preclude scale-up of notification of TB by private practitioners. PMID- 26376199 TI - Two Years Since the BRAIN Initiative: Update on Current Scientific and Technological Neuroscience Advancements. PMID- 26376198 TI - Ultrasensitive and Broadband MoS2 Photodetector Driven by Ferroelectrics. AB - A few-layer MoS2 photodetector driven by poly(vinylidene fluoride trifluoroethylene) ferroelectrics is achieved. The detectivity and responsitivity are up to 2.2 * 10(12) Jones and 2570 A W(-1), respectively, at 635 nm with ZERO gate bias. E(g) of MoS2 is tuned by the ultrahigh electrostatic field from the ferroelectric polarization. The photoresponse wavelengths of the photodetector are extended into the near-infrared (0.85-1.55 MUm). PMID- 26376200 TI - Activating Spinal Interneurons for Neural Repair After Spinal Cord Injury. PMID- 26376201 TI - We Will Use Antiplatelets As Our First Choice for Prevention of Stroke Recurrence in Cervical Arterial Dissection After Reading CADISS--Will You? PMID- 26376202 TI - Conformational Switching by Vibrational Excitation of a Remote NH Bond. AB - Here we describe an unprecedented reversible interconversion between two conformational states, accomplished by selective vibrational excitation of a bond remotely located in relation to the isomerizing fragment. In contrast to previous studies reporting conformational changes via vibrational excitation of a nearby OH group, in this study the transformations were successfully achieved by excitation of a distant NH stretching coordinate. The syn and anti forms of monomeric 6-methoxyindole, which differ in the orientation of the methoxy group, were trapped in low-temperature inert matrixes and characterized spectroscopically. These forms could be selectively shifted in both directions by using near-IR excitations tuned at the frequency of the first NH stretching overtone. The observed isomerization proves the possibility of efficient vibrational relaxation to carry the energy deposited at the NH stretching coordinate into the reactive C-O torsional mode localized on the methoxy group four bonds away from the excited NH moiety. PMID- 26376203 TI - Restoration of the Occlusal Vertical Dimension with an Overlay Removable Partial Denture: A Clinical Report. AB - The process of tooth loss throughout life associated with severe occlusal wear may pose a challenge in the rehabilitation of partially edentulous arches. In these cases, many therapeutic procedures are necessary because each tooth must be restored to obtain the correct anatomical contour and recover the occlusal vertical dimension (OVD). A removable partial denture (RPD) with occlusal/incisal coverage, also known as an overlay RPD, is an alternative treatment option with fewer interventions, and, consequently, lower cost. This clinical report reviews the principles involved in the clinical indication for an overlay RPD, as well as the necessary planning and execution, to discuss the feasibility and clinical effectiveness of this treatment, identifying the indications, advantages, and disadvantages of this procedure through the presentation of a clinical case. The overlay RPD can be an alternative treatment for special situations involving partially edentulous arches in patients who need reestablishment of the OVD and/or realignment of the occlusal plane, and it can be used as a temporary or definitive treatment. The main advantages of this type of treatment are its simplicity, reversibility, and relatively low cost; however, further studies are needed to ensure the efficacy of this treatment option. PMID- 26376204 TI - Diversification of Nitrogen Sources in Various Tundra Vegetation Types in the High Arctic. AB - Low nitrogen availability in the high Arctic represents a major constraint for plant growth, which limits the tundra capacity for carbon retention and determines tundra vegetation types. The limited terrestrial nitrogen (N) pool in the tundra is augmented significantly by nesting seabirds, such as the planktivorous Little Auk (Alle alle). Therefore, N delivered by these birds may significantly influence the N cycling in the tundra locally and the carbon budget more globally. Moreover, should these birds experience substantial negative environmental pressure associated with climate change, this will adversely influence the tundra N-budget. Hence, assessment of bird-originated N-input to the tundra is important for understanding biological cycles in polar regions. This study analyzed the stable nitrogen composition of the three main N-sources in the High Arctic and in numerous plants that access different N-pools in ten tundra vegetation types in an experimental catchment in Hornsund (Svalbard). The percentage of the total tundra N-pool provided by birds, ranged from 0-21% in Patterned-ground tundra to 100% in Ornithocoprophilous tundra. The total N-pool utilized by tundra plants in the studied catchment was built in 36% by birds, 38% by atmospheric deposition, and 26% by atmospheric N2-fixation. The stable nitrogen isotope mixing mass balance, in contrast to direct methods that measure actual deposition, indicates the ratio between the actual N-loads acquired by plants from different N-sources. Our results enhance our understanding of the importance of different N-sources in the Arctic tundra and the used methodological approach can be applied elsewhere. PMID- 26376205 TI - Effects of lipopolysaccharide on the expression of plasma membrane monoamine transporter (PMAT) at the blood-brain barrier and its implications to the transport of neurotoxins. AB - Plasma membrane monoamine transporter (PMAT) is a polyspecific organic cation transporter that is highly expressed in the central nervous system. This study aimed to investigate the effect of lipopolysaccharide on PMAT expression at the blood-brain barrier and the interaction between PMAT and neurotoxins. As a result, PMAT mRNA was identified in brain microvessels (BMVs), brain microvascular endothelial cells (BMECs), astrocytes, and pericytes isolated from C57BL/6 mice and/or Wistar rats using RT-qPCR. The immunofluorescence staining confirmed the expression of PMAT protein in BMVs and striatum of C57BL/6 mice. Western blotting demonstrated its localization at the luminal and abluminal sides of BMECs. In C57BL/6 mice, PMAT protein was significantly increased in BMVs 24 h after an intraperitoneal injection of 3 mg/kg lipopolysaccharide. Lipopolysaccharide treatment also significantly increased PMAT expression in cerebral cortex and the striatum in a time-dependent manner, as well as the brain to-plasma ratio of 1-benzyl-1,2,3,4-tetrahydroisoquinoline (1-benzyl-TIQ). In isolated cells, lipopolysaccharide treatment significantly increased PMAT mRNA in brain astrocytes and the BMECs co-cultured with astrocytes. In addition to 1 methyl-4-phenylpyridinium, the kinetic study indicated that both 1-methyl-4 phenyl-1,2,3,6-tetrahydropyridine and 1-benzyl-TIQ are substrates of human PMAT. These findings suggest that inflammation can change PMAT expression at the blood brain barrier, which may affect PMAT-mediated transport of neurotoxins. We demonstrated the expression of plasma membrane monoamine transporter (PMAT; mRNA or protein) at several subunits of the blood-brain barrier. Lipopolysaccharide treatment can significantly increase the expression of PMAT in vivo (in brain microvessels, cerebral cortex, and the striatum of C57BL/6 mice) and in vitro (in brain astrocytes and brain microvascular endothelial cells co-cultured with astrocytes). Lipopolysaccharide treatment also increased the brain-to-plasma ratio of 1-benzyl-1,2,3,4-tetrahydroisoquinoline (1-benzyl-TIQ) in mice, where 1 benzyl-TIQ competitively inhibited 1-methyl-4-phenylpyridinium (MPP(+)) uptake in MDCK-human PMAT (hPMAT) cells and its uptake in MDCK-hPMAT is concentration dependent. PMID- 26376206 TI - Development of in Silico Models for Predicting P-Glycoprotein Inhibitors Based on a Two-Step Approach for Feature Selection and Its Application to Chinese Herbal Medicine Screening. AB - P-glycoprotein (P-gp) is regarded as an important factor in determining the ADMET (absorption, distribution, metabolism, elimination, and toxicity) characteristics of drugs and drug candidates. Successful prediction of P-gp inhibitors can thus lead to an improved understanding of the underlying mechanisms of both changes in the pharmacokinetics of drugs and drug-drug interactions. Therefore, there has been considerable interest in the development of in silico modeling of P-gp inhibitors in recent years. Considering that a large number of molecular descriptors are used to characterize diverse structural moleculars, efficient feature selection methods are required to extract the most informative predictors. In this work, we constructed an extensive available data set of 2428 molecules that includes 1518 P-gp inhibitors and 910 P-gp noninhibitors from multiple resources. Importantly, a two-step feature selection approach based on a genetic algorithm and a greedy forward-searching algorithm was employed to select the minimum set of the most informative descriptors that contribute to the prediction of P-gp inhibitors. To determine the best machine learning algorithm, 18 classifiers coupled with the feature selection method were compared. The top three best-performing models (flexible discriminant analysis, support vector machine, and random forest) and their ensemble model using respectively only 3, 9, 7, and 14 descriptors achieve an overall accuracy of 83.2%-86.7% for the training set containing 1040 compounds, an overall accuracy of 82.3%-85.5% for the test set containing 1039 compounds, and a prediction accuracy of 77.4%-79.9% for the external validation set containing 349 compounds. The models were further extensively validated by DrugBank database (1890 compounds). The proposed models are competitive with and in some cases better than other published models in terms of prediction accuracy and minimum number of descriptors. Applicability domain then was addressed by developing an ensemble classification model to obtain more reliable predictions. Finally, we employed these models as a virtual screening tool for identifying potential P-gp inhibitors in Traditional Chinese Medicine Systems Pharmacology (TCMSP) database containing a total of 13 051 unique compounds from 498 herbs, resulting in 875 potential P-gp inhibitors and 15 inhibitor-rich herbs. These predictions were partly supported by a literature search and are valuable not only to develop novel P-gp inhibitors from TCM in the early stages of drug development, but also to optimize the use of herbal remedies. PMID- 26376207 TI - Skin mucus proteome map of European sea bass (Dicentrarchus labrax). AB - Skin mucus is the first barrier of fish defence. Proteins from skin mucus of European sea bass (Dicentrarchus labrax) were identified by 2DE followed by LC MS/MS. From all the identified proteins in the proteome map, we focus on the proteins associated with several immune pathways in fish. Furthermore, the real time PCR transcript levels in skin are shown. Proteins found include apolipoprotein A1, calmodulin, complement C3, fucose-binding lectin, lysozyme and several caspases. To our knowledge, this is the first skin mucus proteome study and further transcriptional profiling of the identified proteins done on this bony fish species. This not only contributes knowledge on the routes involved in mucosal innate immunity, but also establishes a non-invasive technique based on locating immune markers with a potential use for prevention and/or diagnosis of fish diseases. PMID- 26376208 TI - The circadian clock controls fluctuations of colonic cell proliferation during the light/dark cycle via feeding behavior in mice. AB - The mammalian circadian system is controlled not only by the suprachiasmatic nucleus (SCN), but also by the peripheral clocks located in tissues such as liver, kidney, small intestine, and colon, mediated through signals such as hormones. Peripheral clocks, but not the SCN, can be entrained by food intake schedules. While it is known that cell proliferation exhibits a circadian rhythm in the colon epithelium, it is unclear how this rhythm is influenced by food intake schedules. Here, we aimed to determine the relationships between feeding schedules and cell proliferation in the colon epithelium by means of immunochemical analysis, using 5-bromo-2'-deoxyuridine (BrdU), as well as to elucidate how feeding schedules influence the colonic expression of clock and cell cycle genes, using real-time reverse-transcription PCR (qRT-PCR). Cell proliferation in the colonic epithelium of normal mice exhibited a daily fluctuation, which was abrogated in Clock mutant mice. The day/night pattern of cellular proliferation and clock gene expression under daytime and nighttime restricted feeding (RF) schedules showed opposite tendencies. While daytime RF for every 4 h attenuated the day/night pattern of cell proliferation, this was restored to normal in the Clock mutant mice under the nighttime RF schedule. These results suggest that feeding schedules contribute to the establishment of a daily fluctuation of cell proliferation and RF can recover it in Clock mutant mice. Thus, this study demonstrates that the daily fluctuation of cell proliferation in the murine colon is controlled by a circadian feeding rhythm, suggesting that feeding schedules are important for rhythmicity in the proliferation of colon cells. PMID- 26376209 TI - The miR-30a Negatively Regulates IL-17-Mediated Signal Transduction by Targeting Traf3ip2. AB - Interleukin-17 (IL-17) has been proved to be involved in the pathogenesis of several autoimmune diseases, including lupus, rheumatoid arthritis, multiple sclerosis, and inflammatory bowel disease. The regulation of IL-17 signal transduction is less studied. miR-30a has been identified to be downregulated in these human autoimmune diseases and their related animal models. However, how it functions in IL-17-mediated inflammation and the pathogenesis of these diseases remain unknown. In this study, we showed that miR-30a inhibits IL-17-mediated NF kappaB and MAPK activation, leading to the reduced production of inflammatory cytokines and chemokines. miR-30a also reduced mRNA stability triggered by IL-17 stimulation. These suppressive effects of miR-30a were mediated by directly targeting Traf3ip2 mRNA (coding for Act1). Thus, we concluded that the downregulation of miR-30a in autoimmune diseases may exacerbate IL-17-mediated inflammation, which may serve as a potential target for the therapy of these diseases. PMID- 26376210 TI - Variation in Primary Care Service Patterns by Rural-Urban Location. AB - BACKGROUND: Rural communities have disproportionately faced primary care shortages for decades in spite of policy efforts to prepare and attract primary care health professionals to practice in rural locales. Insight into how primary care physicians' service patterns in rural areas differ from those in less rural places is important to better inform recruitment strategies that target primary care providers and rural communities. OBJECTIVES: The purpose of this research is to describe how primary care physician service patterns vary by rural-urban location for a large, privately insured population. We discuss implications of service pattern variation on policy efforts to attract primary care providers to underserved rural areas. METHODS: Claims data from fully insured commercial health insurance beneficiaries were used to develop service pattern profiles for primary care providers located in 1 of 4 types of rural-urban areas in Iowa in 2009. The 4 area types are metropolitan, micropolitan, noncore area adjacent to a metro area, and noncore/nonadjacent rural area. RESULTS: There were differences in primary care physicians' service patterns by rural-urban area type. Physicians in nonmetropolitan areas provided relatively more care on a per physician basis than those in the metropolitan area type, as well as more surgery, maternity, emergency, and nursing facility services than metropolitan physicians. CONCLUSION: Primary care physicians who value practicing a relatively diverse range of services may find locating in rural areas an appealing choice. Health systems and policy makers seeking to attract primary care physicians to rural areas can incorporate this reality into a recruitment strategy. PMID- 26376211 TI - Etiology of Appendicitis in Children: The Role of Bacterial and Viral Pathogens. AB - BACKGROUND: Although acute appendicitis is the most common cause for abdominal surgery in children, its etiology is still largely unknown. The aim of this study was to evaluate the role of bacterial and viral pathogens for the etiology of appendicitis in children. METHODS: Between 2000 and 2010, 277 children underwent appendectomy in our institution. On this collective, a retrospective study was performed on to identify the presence of bacterial or viral pathogens. RESULTS: Intraoperatively, 39% of cases showed acute, 9% of cases chronic, and 41% of cases ulcerous inflammation. Bowel perforation was found in 7% of cases and four percent of the children had no inflammation of the appendix at all. Escherichia coli was the predominant bacterium with an incidence of 27.4%, followed by streptococci (9.8%). Concerning viral pathogens, adenovirus was the most common with an incidence of 5.4% followed by rotavirus (4.7%). Significant correlations between histopathological findings and present pathogens were found: in cases of bowel perforation there were significantly more infections with E. coli bacteria (32.2%, p < .001), streptococci (12.2%, p < 0.001), and Pseudomonas aeruginosa (6.7%, p < .001) whereas chronic inflammations were accompanied with a significantly elevated rate of yersinia infections (2.5%, p = .016). Acute inflammations were significantly more often associated with campylobacter (1.7%, p = .011) and oxyures infections (6.1%, p < .001). In relation to the patients' age, a significant accumulation of different pathogens was observed. CRP- and leukocyte counts showed differences between viral and bacterial inflammations. CONCLUSIONS: Our data indicates that appendicitis in children might be triggered by bacterial and viral pathogens and that the type of pathogen directly correlates with patient age, type of inflammation, and level of inflammation values. To confirm and further evaluate these findings, additional studies need to be conducted. PMID- 26376212 TI - Rutosides for treatment of post-thrombotic syndrome. AB - BACKGROUND: Post-thrombotic syndrome (PTS) is a long-term complication of deep venous thrombosis (DVT) that is characterised by pain, swelling, and skin changes in the affected limb. One in three patients with DVT will develop post-thrombotic sequelae within five years. Rutosides are a group of compounds derived from horse chestnut (Aesculus hippocastanum), a traditional herbal remedy for treating oedema formation in chronic venous insufficiency (CVI). However, it is not known whether rutosides are effective and safe in the treatment of PTS. This is an update of the review first published in 2013. OBJECTIVES: To determine the effectiveness (improvement or deterioration in symptoms) and safety of rutosides for treatment of post-thrombotic syndrome (PTS) in patients with DVT compared to placebo, no intervention, elastic compression stockings (ECS) or any other treatment. SEARCH METHODS: For this update the Cochrane Vascular Group Trials Search Co-ordinator searched the Specialised Register (last searched September 2015) and the Cochrane Register of Studies (CRS) (CENTRAL (2015, Issue 8)). Clinical trials databases were searched for details of ongoing and unpublished studies. SELECTION CRITERIA: Two review authors (JM and DNK) independently assessed studies for inclusion. Studies were included to allow the comparison of rutosides versus placebo or no treatment, rutosides versus ECS, and rutosides versus any other treatment. Two review authors (JM and SEY) extracted information from the trials. Disagreements were resolved by discussion. DATA COLLECTION AND ANALYSIS: Data were extracted using designated data extraction forms. The Cochrane risk of bias tool was used for all included studies to assist in the assessment of quality. Primary outcome measures were the occurrence of leg ulceration over time (yes or no) and any improvement or deterioration of post thrombotic syndrome (yes or no). Secondary outcomes included reduction of oedema, pain, recurrence of deep venous thrombosis or pulmonary embolism, compliance with therapy, and adverse effects. All of the outcome measures were analysed using Mantel-Haenzel fixed-effect model odds ratios. The unit of analysis was the number of patients. MAIN RESULTS: Ten reports of nine studies were identified following searching and three studies with a total of 233 participants met the inclusion criteria. Overall quality of the evidence using the GRADE approach was low or very low, predominantly due to the lack of both participant and researcher blinding in the included studies. The quality of the evidence was further limited as only three small studies contributed to the review findings. A subjective scoring system was used to obtain the symptoms of PTS so it was important that the assessors were blinded to the intervention. One study compared rutoside with placebo, one study compared rutosides with ECS and rutosides plus ECS versus ECS alone, and one study compared rutosides with an alternative venoactive remedy. Occurrence of leg ulceration was not reported in any of the included studies. There was a 29% odds of an improvement in PTS in the rutoside treated group versus placebo or no treatment, and lower rates of improvement in PTS in the rutoside treated group when compared with ECS, however these were statistically non-significant. Lower rates of improvement in PTS were shown in the rutoside treated group when compared with an alternative venoactive remedy. More PTS deterioration was shown in the placebo or no treatment group when compared with rutosides but this was not statistically significant. Compared with ECS, rutosides showed higher odds of PTS deterioration but this was also not statistically significant. One study reported on adverse effects showing higher odds of mild adverse effects in the rutoside treated group compared to placebo but this was not statistically significant. AUTHORS' CONCLUSIONS: There was no evidence that rutosides were superior to the use of placebo or ECS. Overall, there is currently limited and low or very low quality evidence that 'venoactive' or 'phlebotonic' remedies such as rutosides reduce symptoms of PTS. Mild side effects were noted in one study. The three studies included in this review provide no evidence for the use of rutosides in the treatment of PTS. PMID- 26376213 TI - Mothers' physical interventions in toddler play in a low-income, African American sample. AB - This mixed method study examined 28 low-income African American mothers' physical interventions in their 14-month-old toddlers' play. Inductive methods were used to identify six physical intervention behaviors, the affect accompanying physical interventions, and apparent reasons for intervening. Nonparametric statistical analyses determined that toddlers experienced physical intervention largely in the context of positive maternal affect. Mothers of boys expressed highly positive affect while physically intervening more than mothers of girls. Most physically intervening acts seemed to be motivated by maternal intent to show or tell children how to play or to correct play deemed incorrect. Neutral affect was the most common toddler affect type following physical intervention, but boys were more likely than girls to be upset immediately after physical interventions. Physical interventions intended to protect health and safety seemed the least likely to elicit toddler upset. PMID- 26376214 TI - Advances in Pediatric Intravenous Iron Therapy. AB - Iron deficiency anemia (IDA) continues to be very common worldwide. Intravenous (IV) iron is an infrequently used therapeutic option in children with IDA despite numerous studies in adults and several small but notable pediatric studies showing efficacy and safety. Presently, the availability of newer IV iron products allows for replacement of the total iron deficit at a single setting. These products appear safer compared to the high molecular weight iron dextrans of the past. Herein, we review the medical literature and suggest that front line use of IV iron should be strongly considered in diseases associated with IDA in children. PMID- 26376215 TI - Phosphorylation of TRPV1 by cyclin-dependent kinase 5 promotes TRPV1 surface localization, leading to inflammatory thermal hyperalgesia. AB - Cyclin-dependent kinase 5 (Cdk5) is an important serine/threonine kinase that plays critical roles in many physiological processes. Recently, Cdk5 has been reported to phosphorylate TRPV1 at threonine 407 (Thr-407) in humans (Thr-406 in rats), which enhances the function of TRPV1 channel and promotes thermal hyperalgesia in the complete Freund's adjuvant (CFA)-induced inflammatory pain rats. However, the underlying mechanisms are still unknown. Here, we demonstrate that Cdk5 phosphorylates TRPV1 at Threonine 406 and promotes the surface localization of TRPV1, leading to inflammatory thermal hyperalgesia. The mutation of Thr-406 of TRPV1 to alanine reduced the interaction of TRPV1 with the cytoskeletal elements and decreased the binding of TRPV1 with the motor protein KIF13B, which led to reduced surface distribution of TRPV1. Disrupting the phosphorylation of TRPV1 at Thr-406 dramatically reduced the surface level of TRPV1 in HEK 293 cells after transient expression and the channel function in cultured dorsal root ganglion (DRG) neurons. Notably, intrathecal administration of the interfering peptide against the phosphorylation of Thr-406 alleviated heat hyperalgesia and reduced the surface level of TRPV1 in inflammatory pain rats. Together, these results demonstrate that Cdk5-mediated phosphorylation of TRPV1 at Thr-406 increases the surface level and the function of TRPV1, while the TAT T406 peptide can effectively attenuate thermal hyperalgesia. Our studies provide a potential therapy for inflammatory pain. PMID- 26376216 TI - Bulleyaconitine A depresses neuropathic pain and potentiation at C-fiber synapses in spinal dorsal horn induced by paclitaxel in rats. AB - Paclitaxel, a widely used chemotherapeutic agent, often induces painful peripheral neuropathy and at present no effective drug is available for treatment of the serious side effect. Here, we tested if intragastrical application of bulleyaconitine A (BLA), which has been approved for clinical treatment of chronic pain in China since 1985, could relieve the paclitaxel-induced neuropathic pain. A single dose of BLA attenuated the mechanical allodynia, thermal hyperalgesia induced by paclitaxel dose-dependently. Repetitive administration of the drug (0.4 and 0.8 mg/kg, t.i.d. for 7 d) during or after paclitaxel treatment produced a long-lasting inhibitory effect on thermal hyperalgesia, but not on mechanical allodynia. In consistency with the behavioral results, in vivo electrophysiological experiments revealed that spinal synaptic transmission mediated by C-fiber but not A fiber was potentiated, and the magnitude of long-term potentiation (LTP) at C-fiber synapses induced by the same high frequency stimulation was ~50% higher in paclitaxel-treated rats, compared to the naive rats. Spinal or intravenous application of BLA depressed the spinal LTP, dose-dependently. Furthermore, patch clamp recordings in spinal cord slices revealed that the frequency but not amplitude of both spontaneous excitatory postsynaptic current (sEPSCs) and miniature excitatory postsynaptic currents (mEPSCs) in lamina II neurons was increased in paclitaxel-treated rats, and the superfusion of BLA reduced the frequency of sEPSCs and mEPSCs in paclitaxel treated rats but not in naive ones. Taken together, we provide novel evidence that BLA attenuates paclitaxel-induced neuropathic pain and that depression of spinal LTP at C-fiber synapses via inhibiting presynaptic transmitter release may contribute to the effect. PMID- 26376219 TI - 3D/4D sonography - any safety problem. AB - Gray-scale image data are processed in 3D ultrasound by repeated scans of multiple planes within a few seconds to achieve one surface rendering image and three perpendicular plane images. The 4D image is achieved by repeating 3D images in short intervals, i.e. 3D and 4D ultrasound are based on simple B-mode images. During 3D/4D acquisition, a fetus in utero is exposed by ultrasound beam for only a few seconds, and it is as short as real-time B-mode scanning. Therefore, simple 3D imaging is as safe as a simple B-mode scan. The 4D ultrasound is also as safe as a simple B-mode scan, but the ultrasound exposure should be shorter than 30 min. The thermal index (TI) and mechanical index (MI) should both be lower than 1.0, and the ultrasound study is regulated by the Doppler ultrasound if it is combined with simple 3D or 4D ultrasound. Recently, some articles have reported the functional changes of animal fetal brain neuronal cells and liver cell apoptosis with Doppler ultrasound. We discuss cell apoptosis by ultrasound in this report. Diagnostic ultrasound safety is achieved by controlling the output pulse and continuous ultrasound waves using thermal and mechanical indices, which should be <1.0 in abdominal and transvaginal scan, pulsed Doppler, as well as 3D and 4D ultrasound. The lowest spatial peak temporal average (SPTA) intensity of the ultrasound to suppress cultured cell growth is 240 mW/cm2, below which no ultrasound effect has been reported. An ultrasound user must be trained to recognize the ultrasound bioeffects; thermal and mechanical indices, and how to reduce these when they are higher than 1.0 on the monitor display; and guide the proper use of the ultrasound under the ALARA principle, because the user is responsible for ensuring ultrasound safety. PMID- 26376217 TI - Sex differences in cell genesis, hippocampal volume and behavioral outcomes in a rat model of neonatal HI. AB - Hypoxia-ischemia (HI) of the brain in near-term and term infants is a leading cause of infant mortality and lifelong disability but current therapeutic approaches remain limited. Males consistently display greater vulnerability to the deleterious consequences of HI in both humans and animal models. Neurogenesis increases after neonatal HI and offers a potential therapeutic target for recovery. The steroid hormone estradiol has been extensively explored as a neuroprotectant in adult models of stroke but with mixed results. Less consideration has been afforded to this naturally occurring agent in the developing brain, which has unique challenges from the adult. Using a model of term HI in the rat we have explored the impact of this insult on cell genesis in the hippocampus of males and females and the ability of estradiol treatment immediately after insult to restore function. Both short-term (3 days) and long term (7 days) post-injury were assessed and revealed that only females had markedly increased cell genesis on the short-term but both sexes were increased long-term. A battery of behavioral tests revealed motor impairment in males and compromised episodic memory while both sexes were modestly impaired in spatial memory. Juvenile social play was also depressed in both sexes after HI. Estradiol therapy improved behavioral performance in both sexes but did not reverse a deficit in hippocampal volume ipsilateral to the insult. Thus the effects of estradiol do not appear to be via cell death or proliferation but rather involve other components of neural functioning. PMID- 26376220 TI - Different patterns of 5-HT receptor and transporter dysfunction in neuropsychiatric disorders--a comparative analysis of in vivo imaging findings. AB - Impairment of serotonin receptor and transporter function is increasingly recognized to play a major role in the pathophysiology of neuropsychiatric diseases including anxiety disorder (AD), major depressive disorder (MDD), bipolar disorder (BD) and schizophrenia (SZ). We conducted a PubMed search, which provided a total of 136 in vivo studies with PET and SPECT, in which 5-HT synthesis, 5-HT transporter binding, 5-HT1 receptor binding or 5-HT2 receptor binding in patients with the primary diagnosis of acute AD, MDD, BD or SZ was compared to healthy individuals. A retrospective analysis revealed that AD, MDD, BD and SZ differed as to affected brain region(s), affected synaptic constituent(s) and extent as well as direction of dysfunction in terms of either sensitization or desensitization of transporter and receptor binding sites. PMID- 26376221 TI - Absolute Quantitation of Intact Recombinant Antibody Product Variants Using Mass Spectrometry. AB - Accurate and precise quantitative measurement of product-related variants of a therapeutic antibody is essential for product development and testing. Bispecific antibodies (bsAbs) are Abs composed of two different half antibody arms, each of which recognizes a distinct target, and recently they have attracted substantial therapeutic interest. Because of the increased complexity of its structure and its production process, as compared to a conventional monoclonal antibody, additional product-related variants, including covalent and noncovalent homodimers of half antibodies (hAbs), may be present in the bsAb product. Sufficient separation and reliable quantitation of these bsAb homodimers using liquid chromatography (LC) or capillary electrophoresis-based methods is challenging because these homodimer species and the bsAb often have similar physicochemical properties. Formation of noncovalent homodimers and heterodimers can also occur. In addition, since homodimers share common sequences with their corresponding halves and bsAb, it is not suitable to use peptides as surrogates for their quantitation. To tackle these analytical challenges, we developed a mass spectrometry-based quantitation method. Chip-based nanoflow LC-time-of flight mass spectrometry coupled with a standard addition approach provided unbiased absolute quantitation of these drug-product-related variants. Two methods for the addition of known levels of standard (multi- or single-addition) were evaluated. Both methods demonstrated accurate and reproducible quantitation of homodimers at the 0.2% (w/w) level, with the single-addition method having the promise of higher analytical throughput. PMID- 26376222 TI - Upper gastrointestinal Kaposi's sarcoma in HIV-infected patients: ten years of endoscopy observation at a single Brazilian center. AB - BACKGROUND: Kaposi's sarcoma (KS) is the most common neoplasm among HIV-infected individuals. The frequency of involvement of KS in the gastrointestinal (GI) tract and the associated epidemiological, immune, endoscopic, and histopathological features in HIV-infected patients, were evaluated in this study. METHODS: A review of the medical and endoscopy reports of 1428 HIV infected patients, who had undergone upper GI endoscopy at the Endoscopy Service, Clinical Hospital, Faculty of Medicine of Ribeirao Preto between January 1999 and June 2009, was performed. Clinical, epidemiological, immunological, endoscopic, and histological data were collected. RESULTS: Twenty-seven (1.9%) patients were diagnosed with GI KS. Patients were predominantly male (81.5%). Sexual activity was the main route of HIV transmission (81.5%). Cutaneous involvement was noted in 21 patients (78%). Fifteen patients (55%) received highly active antiretroviral therapy for a mean duration of 12.6 weeks (range 2-52 weeks) before endoscopy. GI lesions were mainly found in the stomach (55%). Analysis of the immunohistochemical methods HHV8 LNA-1, CD31, and CD34 for the diagnosis of gastric KS indicated high agreement (kappa=0.63, 95% confidence interval 0.32 0.94). There was no relationship between CD4 levels (p=0.34) or HIV viral load (p=0.99) and HHV8 LNA-1 positivity in gastric KS. CONCLUSIONS: GI KS is an infrequent finding in patients with HIV infection. Among those with GI KS, 80% had concomitant skin lesions. Immunohistochemical methods for CD31, CD34, and LNA 1 were important tools in the diagnostic assessment of lesions suggestive of KS in the GI tract. Further studies are required to confirm these data, and the need for routine endoscopic investigation of the GI tract in HIV-infected patients with cutaneous KS should be assessed. PMID- 26376223 TI - Retrospective study of risk factors for mortality in human avian influenza A(H7N9) cases in Zhejiang Province, China, March 2013 to June 2014. AB - BACKGROUND: The influenza A(H7N9) virus causes a serious disease that threatens human health. Fatalities associated with human infections caused by this virus are of great public health concern; however, the possible risk factors are not yet fully known. METHODS: A stratified sampling method, incorporating household income levels and a random number table method, was used to select laboratory confirmed A(H7N9) cases for this study. Eighty-five patients were selected randomly from 139 laboratory-confirmed A(H7N9) cases occurring in Zhejiang Province between March 1, 2013 and June 30, 2014. Data were collected using a standard method. To test the statistical significance among discrete variables, univariate analyses were used to compare two groups. The Kaplan-Meier product limit method was used to analyze the patient survival fraction. The Cox proportional hazards regression model was used to analyze all variables with p <= 0.05 in the univariate analysis. Lastly, a stepwise procedure was used to construct a final model with a significance level of p > 0.10 for removal and p<0.05 for re-entry. RESULTS: A total of 85 patients with H7N9 virus infection were identified. Among these, 30 (35.29%) died. In the univariate analysis, the following factors were associated with a high risk of influenza A(H7N9) case fatality: age >= 60 years (p=0.008), low education level (p=0.030), chronic diseases (p=0.029), poor hand hygiene (p=0.010), time from illness onset to the first medical visit (p=0.029) and to intensive care unit admission (p=0.008), an incubation period of <= 5 days (p=0.039), a peak C-reactive protein >= 120 mg/l (p=0.012), increased initial neutrophil count (p=0.020), decreased initial lymphocyte count (p=0.021), and initial infection of both lungs (p=0.003). Multivariate analysis confirmed that the independent predictors of H7N9 virus infection mortality in Zhejiang, China were hand hygiene (hazard ratio (HR) 5.163, 95% confidence interval (CI) 1.164-22.661), age (HR 1.042, 95% CI 1.007 1.076), and peak CRP (HR 1.009, 95% CI 1.002-1.016). CONCLUSIONS: Improvements in immunity, early case identification and treatment, and personal protection measures are key to addressing the high human avian influenza A(H7N9) case fatality rate. PMID- 26376224 TI - Molecular evidence that the opportunistic fungal pathogen Trichosporon asahii is part of the normal fungal microbiota of the human gut based on rRNA genotyping. AB - The fungus Trichosporon asahii is distributed widely in the environment and is frequently isolated from clinical specimens. It can cause life-threatening disseminated infections, including breakthrough infection after the administration of candin antifungal drugs. However, the definitive infection route is still unclear. In this study, 43 T. asahii genotypes were detected in 72 fecal samples from healthy subjects. The rRNA genotypes of the species were determined using a culture-independent method. The genotypes of T. asahii were almost identical to those of reported clinical isolates. Therefore, T. asahii colonizing the gastrointestinal tract might be associated with the development of trichosporonosis, and not environmental isolates. PMID- 26376225 TI - Patient-focused and feedback research in psychotherapy: Where are we and where do we want to go? AB - In the last 15 years feedback interventions have had a significant impact on the field of psychotherapy research and have demonstrated their potential to enhance treatment outcomes, especially for patients with an increased risk of treatment failure. This article serves as an introduction to the special issue on "Patient focused and feedback research in psychotherapy: Where are we and where do we want to go?" Current investigations on feedback research are concerned with potential moderators and mediators of these effects, as well as the design and the implementation of feedback into routine care. This introduction summarizes the current state of feedback research and provides an overview of the three main research topics in this issue: (1) How to implement feedback systems into routine practice and how do therapist and patient attitudes influence its effects?, (2) How to design feedback reports and decision support tools?, and (3) What are the reasons for patients to become at risk of treatment failure and how should therapists intervene with these patients? We believe that the studies included in this special issue reflect the current state of feedback research and provide promising pathways for future endeavors that will enhance our understanding of feedback effects. PMID- 26376226 TI - Semen characteristics and refrigeration in free-ranging giant anteaters (Myrmecophaga tridactyla). AB - The giant anteater (Myrmecophaga tridactyla) is considered vulnerable to extinction. Scientific data on the reproductive parameters of this species are scarce. Semen from eight free-ranging giant anteaters was collected to establish its characteristics and the effects of cooling and storage at 5 degrees C after dilution with the BotuCrio extender without cryoprotectant. The ejaculate presented two distinct sequential fractions, including a whitish fraction, which was milky and rich in sperm cells, and a gel fraction, which was colorless, viscous, and azoospermic. The mean +/- standard error of the mean values of the seminal characteristics were as follows: volume of the first fraction, 0.75 +/- 0.1 mL; motility, 75 +/- 2.9%; vigor, 3.2 +/- 0.3; sperm motility index, 68.8 +/- 4.3; concentration, 108.5 +/- 13.4 * 10(6)/mL; plasma membrane integrity index, 71 +/- 4.0%; spermatic defects detected using modified Karras staining, 35.5 +/- 3.3%; and spermatic alterations identified by differential interference contrast microscopy, 48.3 +/- 6.8%. During refrigeration, the semen presented decreasing motility from 0 to 18 hours, sperm motility index decreased from 0 to 24 hours, and vigor did not change in the first 6 hours and then decreased to 18 hours. PMID- 26376227 TI - Perinatal Diagnostic Approach to Fetal Skeletal Dysplasias: Six Years Experience of a Tertiary Center. AB - Skeletal dysplasias (SDs) constitute a group of heterogeneous disorders affecting growth morphology of the chondro-osseous tissues. Prenatal diagnosis of SD is a considerable clinical challenge due to phenotypic variability. We performed a retrospective analysis of the fetal autopsies series conducted between January 2006 and December 2012 at our center. SD was detected in 54 (10%) out of 542 fetal autopsy cases which included; 11.1% thanatophoric dysplasia (n = 6), 7.4% achondroplasia (n = 4), 3.7% osteogenesis imperfect (n = 2), 1.9% Jarcho-Levin Syndrome (n = 1), 1.9% arthrogryposis (n = 1), 1.9% Dyggve-Melchior-Clausen syndrome (n = 1), 72.1% of dysostosis cases (n = 39). All SD cases were diagnosed by ultrasonography. In 20 of the cases, amniocentesis was performed, 4 cases underwent molecular genetic analyses. Antenatal identification of dysplasia is important in the management of pregnancy and in genetic counseling. Our data analysis showed that SD is usually detected clinically after the 20th gestational week. Genetic analyses for SD may provide early diagnosis and management. PMID- 26376229 TI - Perceived Challenges to the Sustainability of Community-Based Aging Initiatives: Findings from a National Study of Villages. AB - Concerns have been raised regarding the sustainability of Villages, a rapidly expanding set of organizations that typically use a participant-directed approach to improve older adults' quality of life and ability to age in place. Using online survey and telephone-interview data from a 2013 follow-up study of Villages across the United States, this study examined organizational leaders' perceptions of the major challenges to sustainability. Major challenges identified included: (a) funding, (b) membership recruitment, (c) leadership development, (d) meeting members' service needs, and (e) limitations of the Village model itself. Findings point to a number of important considerations for the development, implementation, and sustainability of the Village model, including the role of social workers in addressing these challenges. PMID- 26376228 TI - Prognostic significance of NPM1 mutation-modulated microRNA-mRNA regulation in acute myeloid leukemia. AB - Distinct microRNA (miRNA) and mRNA signatures were reported in nucleophosmin (NPM1)-mutated acute myeloid leukemia (AML). However, it remains unknown whether the mutation participates in the dynamic interaction between miRNA and mRNA. In this study, we aimed to investigate the role of NPM1 mutation in modulating miRNA mRNA regulation (MMR). From the sample-paired miRNA/mRNA microarrays of 181 de novo AML patients, we found that MMR was dynamic and could be affected by NPM1 mutation. By a systematic framework, we identified 493 NPM1 mutation-modulated MMR pairs, where the strength of MMR was significantly attenuated in patients carrying NPM1 mutations, compared to those with wild-type NPM1. These miRNAs/mRNAs were associated with pathways implicated in cancer and known functions of NPM1 mutation. Such modulation of MMR was validated in two independent cohorts as well as in cells with different NPM1 mutant burdens. Furthermore, we showed that the regulatory strength of nine MMR pairs could predict patients' outcomes. Combining these pairs, a scoring system was proposed and shown to predict survival in discovery and validation data sets, independent of other known prognostic factors. Our study provides novel biological insights into the role of NPM1 mutation as a modulator of MMR, based on which a novel prognostic marker is proposed in AML. PMID- 26376230 TI - Validation of quasi-induced exposure representativeness assumption among young drivers. AB - OBJECTIVE: Young driver studies have applied quasi-induced exposure (QIE) methods to assess relationships between demographic and behavioral factors and at-fault crash involvement, but QIE's primary assumption of representativeness has not yet been validated among young drivers. Determining whether nonresponsible young drivers in clean (i.e., only one driver is responsible) 2-vehicle crashes are reasonably representative of the general young driving population is an important step toward ensuring valid QIE use in young driver studies. We applied previously established validation methods to conduct the first study, to our knowledge, focused on validating the QIE representativeness assumption in a young driver population. METHODS: We utilized New Jersey's state crash and licensing databases (2008-2012) to examine the representativeness assumption among 17- to 20-year-old nonresponsible drivers involved in clean multivehicle crashes. It has been hypothesized that if not-at-fault drivers in clean 2-vehicle crashes are a true representation of the driving population, it would be expected that nonresponsible drivers in clean 3-or-more-vehicle crashes also represent this same driving population (Jiang and Lyles 2010 ). Thus, we compared distributions of age, gender, and vehicle type among (1) nonresponsible young drivers in clean 2-vehicle crashes and (2) the first nonresponsible young driver in clean crashes involving 3 or more vehicles to (3) all other nonresponsible young drivers in clean crashes involving 3 or more vehicles. Distributions were compared using chi square tests and conditional logistic regression; analyses were conducted for all young drivers and stratified by license status (intermediate vs. fully licensed drivers), crash location, and time of day of the crash. RESULTS: There were 41,323 nonresponsible drivers in clean 2-vehicle crashes and 6,464 nonresponsible drivers in clean 3-or-more-vehicle crashes. Overall, we found that the distributions of age, gender, and vehicle type were not statistically significantly different between the 3 groups; in each group, approximately one fourth of drivers were represented in each age from age 17 through 20, half were males, and approximately 80% were driving a car/station wagon/minivan. In general, conclusions held when we evaluated the assumption within intermediate and fully licensed young drivers separately and by crash location and time. CONCLUSIONS: It appears that the representativeness assumption holds among the population of young NJ drivers. We encourage young driver studies utilizing QIE methods to conduct internal validation studies to ensure appropriate application of these methods and we propose utilization of QIE methods to address broader foundational and applied questions in young driver safety. PMID- 26376231 TI - The Game Transfer Phenomena Scale: An Instrument for Investigating the Nonvolitional Effects of Video Game Playing. AB - A variety of instruments have been developed to assess different dimensions of playing video games and its effects on cognitions, affect, and behaviors. The present study examined the psychometric properties of the Game Transfer Phenomena Scale (GTPS) that assesses nonvolitional phenomena experienced after playing video games (i.e., altered perceptions, automatic mental processes, and involuntary behaviors). A total of 1,736 gamers participated in an online survey used as the basis for the analysis. Confirmatory factor analysis (CFA) was performed to confirm the factorial structure of the GTPS. The five-factor structure using the 20 indicators based on the analysis of gamers' self-reports fitted the data well. Population cross-validity was also achieved, and the positive associations between the session length and overall scores indicate the GTPS warranted criterion-related validity. Although the understanding of Game Transfer Phenomena is still in its infancy, the GTPS appears to be a valid and reliable instrument for assessing nonvolitional gaming-related phenomena. The GTPS can be used for understanding the phenomenology of post-effects of playing video games. PMID- 26376233 TI - Fever at Diagnosis of Pediatric Acute Lymphoblastic Leukemia: Are Antibiotics Really Necessary? AB - INTRODUCTION: With new multidrug-resistant microbes and the paucity of new antibacterial agents, we must identify opportunities to safely minimize antibiotics. Current guidelines encourage empiric antibiotics in febrile patients with chemotherapy-induced neutropenia to reduce infection-related mortalities. No guidelines exist for children with isolated fever at presentation/diagnosis of acute lymphoblastic leukemia (ALL) and before starting chemotherapy. This study evaluates the incidence of bacteremia in this subpopulation. MATERIALS AND METHODS: We retrospectively analyzed medical records of 230 consecutive patients under 21 years of age diagnosed with ALL at Children's Hospital & Research Center Oakland (CHRCO) from January 2003 through October 2013. We focused on blood cultures obtained within 24 hours of presentation to CHRCO, which was before general anesthesia for a procedure or systemic chemotherapy. RESULTS: Among 221 patients who met the inclusion criteria, 126 (57%) were febrile and had blood cultures obtained. Two patients (1.6%) had positive blood cultures consistent with bacteremia; 1 had group A beta-hemolytic streptococcus and the other had Escherichia coli. DISCUSSION: Given the rarity of bacteremia in this subpopulation at our institution, we recommend more judicious use of antibiotics in children with isolated fever at time of ALL diagnosis. We encourage other institutions to conduct similar investigations. PMID- 26376234 TI - Platelet Mass Predicts Intracranial Hemorrhage in Neonates With Gram-negative Sepsis. AB - Neonatal sepsis due to gram-negative bacteria is associated with severe hemorrhagic conditions, such as intracranial hemorrhage (ICH). The aim of the study was to investigate the significance of platelet (PLT) count and platelet mass (PM) in predicting promptly neonatal ICH. Demographics, species, PLT, PM, ICH, and outcome for neonates with gram-negative sepsis for the period 2005 to 2012 were retrospectively recorded. Eighty-four infants were enrolled with median gestational age 30 weeks, median birthweight 1481.5 g, and median age at sepsis diagnosis 23 days. The most frequently isolated bacteria were Enterobacter spp. (38.1%). ICH occurred in 16 neonates (19%), whereas the mortality rate was 25% (21 neonates). The median PLT count and PM at days 1, 2, and 3 after diagnosis of gram-negative sepsis was significantly associated with the presence of ICH. Regression analysis revealed the cutoff predictive value of 355 fL/nL for the PM at day 3 (area under the curve: 75, sensitivity 90%, P=0.002). PM levels could play an important role in predicting the occurrence of ICH in high-risk neonates. PMID- 26376235 TI - Chronic Myelogenous Leukemia After Therapy for Langerhans Cell Histiocytosis in an Adolescent. PMID- 26376236 TI - The Heart, the Brain, and the Regulation of Emotion. PMID- 26376237 TI - Synergistic effects of rhubarb-gardenia herb pair in cholestatic rats at pharmacodynamic and pharmacokinetic levels. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Herb pair serves as the basic building block of a traditional Chinese medicine (TCM) formula. The rhubarb-gardenia herb pair (RGHP), composed of rhubarb and gardenia, has meaningful clinical effects to cure cholestasis diseases. This study was designed to confirm the expected synergistic effects of RGHP at pharmacodynamic and pharmacokinetic levels. MATERIALS AND METHODS: Thirty male Sprague-Dawley rats were divided into control, model and drug-treated groups. After intragastrically administrated with alpha naphthylisothiocyanate (ANIT) to induce cholestasis, rats were treated with rhubarb, gardenia or RGHP. For pharmacodynamic study, biochemical and histopathological tests were performed to assess the hepatoprotective effects. While for pharmacokinetic study, a LC-MS method was developed for determination of five main chemical markers, namely genipin, rhein, aloe emodin, emodin and chrysophanol in rat plasma. RESULTS: The biochemical and histopathological tests suggested that RGHP exerted enhanced hepatoprotective effects against the ANIT induced cholestasis compared with single herbs. The pharmacokinetic study indicated RGHP could significantly elevate systemic exposure level and prolong retention time of five markers in comparison with rhubarb or gardenia alone. CONCLUSIONS: The present study demonstrated the synergistic effects of RGHP in ANIT-induced cholestatic rats at pharmacodynamic and pharmacokinetic levels, and has significant enlightenments for the rational use of the related TCM formulas containing RGHP. PMID- 26376238 TI - [Malignant lymphoma complicated with posterior reversible encephalopathy]. AB - We present a 56-year-old woman who received chemotherapy for relapsed diffuse large B-cell lymphoma and developed posterior reversible encephalopathy syndrome (PRES) with generalized seizures 27 days after treatment with rituximab, ifosfamide, carboplatin and etoposide (R-ICE). The patient had moderate renal impairment (eGFR > 30 ml/min.) and a normal blood pressure. PRES was confirmed by MRI, which showed oedema of the occipital, parietal and frontal lobes. A control MRI after four weeks showed full remission. To our knowledge this is the first published case of R-ICE causing PRES. PMID- 26376239 TI - [Early diagnosis and treatment of Boerhaave's syndrome is pivotal for the prognosis]. AB - Hydropneumothorax following oesophageal rupture is very rare and often lethal. We report case of a 78-year-old man with known Barret's oesophagus with increasing shortness of breath and right chest pain followed by increasing emesis. Further investigations showed a right side hydropneumothorax and pleural effusion. Thorax and abdominal CT showed middle oesophageal perforation and pneumomediastinum. Oesophageal perforation can lead to pneumothorax and pleural fluid. Early diagnosis is pivotal to reduce mortality. PMID- 26376240 TI - [Fatal course following poisoning with an illegal weight-reducing agent]. AB - DNP is a weight-reducing agent, which has been revived through sale over the Internet. DNP uncouples the oxidative phosphorylation in cells, leading to an excessive production of heat. A 39-year-old male ingested four grams of DNP and developed severe muscular stiffness and eventually cardiac arrest. Intubation was unsuccessful, and tracheotomy was performed on scene. Ventilation proved impossible, and the patient was declared dead in the pre-hospital setting. Doctors need to recognize potential lethal intoxications. Symptomatic treatment is warranted. PMID- 26376241 TI - [Indicator-based HIV testing]. AB - The mortality of HIV-infected patients in Denmark approaches that of the background population. Still, half of the HIV-infected patients are diagnosed late, resulting in poorer response to therapy, larger cost and greater transmission rate. A pan-European initiative, "HIV in Europe" has published a guideline on indicator-based HIV testing in order to improve early HIV diagnosis. The Danish Society of Infectious Diseases wishes to highlight the importance of indicator-based HIV testing, in order to improve the possibility of early diagnosis and therapy of HIV-infection. PMID- 26376242 TI - [Wake therapy for major depression]. AB - Patients admitted with depression are highly tormented and many are suicidal. Standard treatment does not offer full effect until after several weeks. Wake therapy is a method that may reduce depressive symptoms within days. In this paper, the literature regarding wake therapy is reviewed. The response rates in wake therapy are high, but the effect is often transitory. However, recent studies indicate that wake therapy in combination with other chronotherapeutic interventions, e.g. light therapy, can produce a rapid and sustained antidepressant effect. PMID- 26376243 TI - [Splenomegaly and failure to thrive as a result of Gaucher disease]. AB - Gaucher disease (GD) is the most common lysosomal storage disease with a prevalence of 1:75,000. The disease is caused by a defiency of the lysosomal enzyme glucocerebrosidase which leads to an accumulation of the substrate glycosylceramide within macrophages. GD presents with a wide spectrum of symptoms but involvement of the bones, bone marrow and spleen or liver is seen in the majority of patients. We present the case of a ten-year-old girl with massive splenomegaly, cytopenia, poor growth, learning difficulties and extreme fatigue for several years. PMID- 26376244 TI - Object recognition memory in zebrafish. AB - The novel object recognition, or novel-object preference (NOP) test is employed to assess recognition memory in a variety of organisms. The subject is exposed to two identical objects, then after a delay, it is placed back in the original environment containing one of the original objects and a novel object. If the subject spends more time exploring one object, this can be interpreted as memory retention. To date, this test has not been fully explored in zebrafish (Danio rerio). Zebrafish possess recognition memory for simple 2- and 3-dimensional geometrical shapes, yet it is unknown if this translates to complex 3-dimensional objects. In this study we evaluated recognition memory in zebrafish using complex objects of different sizes. Contrary to rodents, zebrafish preferentially explored familiar over novel objects. Familiarity preference disappeared after delays of 5 mins. Leopard danios, another strain of D. rerio, also preferred the familiar object after a 1 min delay. Object preference could be re-established in zebra danios by administration of nicotine tartrate salt (50mg/L) prior to stimuli presentation, suggesting a memory-enhancing effect of nicotine. Additionally, exploration biases were present only when the objects were of intermediate size (2 * 5 cm). Our results demonstrate zebra and leopard danios have recognition memory, and that low nicotine doses can improve this memory type in zebra danios. However, exploration biases, from which memory is inferred, depend on object size. These findings suggest zebrafish ecology might influence object preference, as zebrafish neophobia could reflect natural anti-predatory behaviour. PMID- 26376245 TI - Purinergic mechanisms and prostaglandin E receptors involved in ATP-induced relaxation of porcine retinal arterioles in vitro. AB - PURPOSE: Adenosine triphosphate (ATP) is involved in the tone regulation of retinal arterioles, and the effect may be direct, through ATP degradation or mediated by cyclo-oxygenase products. However, the relative contribution of these mechanisms and the extent to which the mechanisms are active in the retinal vascular wall or depend on the perivascular retinal tissue are unknown. METHODS: Porcine retinal arterioles with perivascular retinal tissue were mounted in a wire myograph for isometric tone recordings. The relaxing effects of ATP and the non-degradable analogue ATP-x03B3;S were studied in the presence of antagonists to ATP, adenosine and prostaglandin E (EP) receptors. The experiments were repeated after removal of the perivascular retinal tissue. RESULTS: ATP induced a significant concentration-dependent relaxation of retinal arterioles (p < 0.05) which was reduced after removal of perivascular retinal tissue. The effect was due to non-degraded ATP and a degradation product of ATP acting via adenosine receptors. Relaxation was reduced by ibuprofen and blocking of EP1 receptors. CONCLUSION: ATP-induced relaxation of retinal arterioles is mediated by ATP, ATP degradation products and by stimulation of EP1 receptors, involving both the perivascular retina and the vascular wall. The findings emphasize the complexity of purinergic effects in the regulation of retinal vascular tone. PMID- 26376246 TI - Integrated Critical Care Organizations: A Personal View. PMID- 26376247 TI - (Sugar-) Sweet Biomarkers? Clinical Proteomics Enters Sepsis Research. PMID- 26376248 TI - Timing Is Everything: Do We Need to Redesign the Afferent Limb in Rapid Response? PMID- 26376249 TI - Caring for Critically Ill Ebola Virus Disease Patients With One Hand Tied Behind Your Back. PMID- 26376250 TI - Sepsis Redux: Bigger and Badder Than Ever. PMID- 26376251 TI - The Future Is Back; Back to the Future! PMID- 26376252 TI - Atrial Fibrillation in Critical Illness: Innocent Bystander or Guilty Party? PMID- 26376253 TI - Stemming Anginal Pain, Waiting for the Magic Cells. PMID- 26376254 TI - Appropriate Antibiotic Treatment in Severe Sepsis and Septic Shock: Timing Is Everything. PMID- 26376255 TI - Evidence to Practice Gap: The Case of Dopamine. PMID- 26376256 TI - Understanding Conflict Between Intensivists and Surgeons. PMID- 26376257 TI - A Few Milliliters of Prevention: Lung-Protective Ventilation Decreases Pulmonary Complications. PMID- 26376258 TI - Searching for the Brain's Canary in the Coal Mine. PMID- 26376259 TI - Mannitol: It is Not Just for Intracranial Pressure Any More! Maybe.... PMID- 26376260 TI - Taking a New Position on Mechanical Ventilation. PMID- 26376261 TI - Molecular Biology Ying Yang in Alveolar Fluid Clearance. PMID- 26376262 TI - Using the Body's Radiator Following Cardiac Arrest: How Cool Is That ...? PMID- 26376263 TI - Risk Factors of Readmissions Among Severe Sepsis Survivors. PMID- 26376264 TI - The authors reply. PMID- 26376265 TI - Pain and Tissue Oxygenation. PMID- 26376266 TI - The authors reply. PMID- 26376267 TI - Association Between Hyperoxia and Mortality After Cardiac Arrest. PMID- 26376268 TI - The authors reply. PMID- 26376269 TI - Early Intervention on Long-Term Outcomes in Critically Ill Cancer: Is There a Disparity of Care? PMID- 26376270 TI - The authors reply. PMID- 26376271 TI - Vasospasm After Pediatric Traumatic Brain Injury: A Difficult Diagnosis. PMID- 26376272 TI - Next Generation of Method-Comparison Studies: Standardization of Data Presentation and Clinical Application Are a Goal to Reach. PMID- 26376273 TI - The authors reply. PMID- 26376274 TI - "Excess Mortality" and Colistin-Tigecycline for Extensively Drug-Resistant Acinetobacter baumannii Bacteremia. PMID- 26376275 TI - Predicting Mortality in Critically Ill Patients. PMID- 26376276 TI - The authors reply. PMID- 26376277 TI - Long-Axis View for Central Venous Access. PMID- 26376278 TI - The authors reply. PMID- 26376279 TI - Ultrasound-Guided Subclavian Vein Catheterization: A Systematic Review and Meta Analysis: Several Facts Need To Be Noticed. PMID- 26376280 TI - The authors reply. PMID- 26376281 TI - Comparison of Clinical Characteristics and Treatment Outcomes of Children Selected for Treatment of Severe Acute Malnutrition Using Mid Upper Arm Circumference and/or Weight-for-Height Z-Score. AB - OBJECTIVES: Debate for a greater role of mid-upper arm circumference (MUAC) measures in nutritional programming continues, but a shift from therapeutic feeding programs admitting children using MUAC and/or weight-for-height Z (WHZ) to a new model admitting children using MUAC only remains complicated by limited information regarding the clinical profile and response to treatment of children selected by MUAC vs. WHZ. To broaden our understanding of how children identified for therapeutic feeding by MUAC and/or WHZ may differ, we aimed to investigate differences between children identified for therapeutic feeding by MUAC and/or WHZ in terms of demographic, anthropometric, clinical, and laboratory and treatment response characteristics. METHODS: Using secondary data from a randomized trial in rural Niger among children with uncomplicated severe acute malnutrition, we compared children that would be admitted to a therapeutic feeding program that used a single anthropometric criterion of MUAC< 115 mm vs. children that are admitted under current admission criteria (WHZ< -3 and/or MUAC< 115 mm) but would be excluded from a program that used a single MUAC< 115 mm admission criterion. We assessed differences between groups using multivariate regression, employing linear regression for continuous outcomes and log-binomial regression for dichotomous outcomes. RESULTS: We found no difference in terms of clinical and laboratory characteristics and discharge outcomes evaluated between children that would be included in a MUAC< 115 mm therapeutic feeding program vs. children that are currently eligible for therapeutic feeding but would be excluded from a MUAC-only program. CONCLUSIONS: A single anthropometric admission criterion of MUAC < 115 mm did not differentiate well between children in terms of clinical or laboratory measures or program outcomes in this context. If nutritional programming is to use a single MUAC-based criterion for admission to treatment, further research and program experience can help to identify the most appropriate criterion in a broad range of contexts to target children in most urgent need of treatment. PMID- 26376282 TI - Synthesis of the Common Core Structure of the Stemofoline Alkaloids. AB - A novel synthetic route to the common core structural motif of the stemofoline alkaloids has been developed. The key transformations include (1) an intramolecular 1,3-dipolar cycloaddition reaction of a highly functionalized nitrone, (2) the subsequent formation of a caged structure via lithiated allylic sulfoxide, and (3) the concomitant sila-Pummerer reaction of alpha-silylalkenyl sulfoxide to prepare a thioester precursor. A series of stereochemistries on the highly caged core structure characteristic of the stemofoline alkaloids was successfully assembled. PMID- 26376283 TI - Urinary PCA3 to predict prostate cancer in a cohort of 1015 patients. AB - AIM: To evaluate the performance of urinary PCA3 test to predict prostate biopsy outcome in a large French cohort. PATIENTS AND METHODS: A urine sample was prospectively obtained in 1015 patients undergoing prostate biopsies to determine the PCA3 score. The predictive value of PCA3 was explored using receiver operating characteristic curve analysis (ROC), multivariable logistic regression analysis and decision curve analysis. RESULTS: The median PCA3 score was significantly higher in patients with positive biopsies. The PCA3 score AUC was 0.76 (0.73-0.79), significantly higher than that of PSA (0.55; 0.51-0.58). At the cut-off of 35, sensitivity was 68 %, specificity 71 %, positive and negative predictive values 67 % and 71 %, and accuracy 69 %. Using multivariate analysis, PCA3 score appeared as an independent predictor of biopsy outcome and its addition to a base model including usual clinico-biological parameters resulted in a significant increase in predictive accuracy. At the cut-off of 20, about 1/2 of the eventual useless biopsies would have been avoided while ignoring 7 % of cancers with Gleason score >= 7. PCA3 score did not correlate to Gleason score but correlated to tumor volume (proportion of invaded cores). CONCLUSION: Urinary PCA3 is a useful test with high diagnostic performance for early prostate cancer diagnosis. Its correlation with cancer aggressiveness seems rather represented by a link to prostate volume than Gleason score. PMID- 26376284 TI - Dexmedetomidine induces conditioned place preference in rats: Involvement of opioid receptors. AB - Dexmedetomidine (DEX) is an alpha-2 adrenergic agonist drug recently introduced to anesthesia practice. Certain agents used in anesthesia practice have been associated with abuse and addiction problems; however, few studies have investigated the role of DEX on addictive processes. Here, the effects and possible mechanisms of action of DEX on conditioned place preference (CPP), a model used for measuring the rewarding effects of drug abuse in rats, was investigated. The CPP apparatus was considered "biased" as the animals preferred the grid side to the mesh side. Male Wistar albino rats weighing 250-300 g were divided into several groups, including control (saline), morphine (10mg/kg), DEX (2.5-20 MUg/kg), naloxone alone (0.5mg/kg) and a combination (0.5mg/kg naloxone plus 20 MUg/kg DEX) (n=7-8 for each group). The CPP effects of morphine, DEX, saline and the combination were evaluated. All the drug and saline administrations except naloxone were performed by intraperitoneal (ip) injections. Naloxone was injected subcutaneously (sc) when given alone or in combination with DEX. Morphine (10mg/kg) and DEX (5-20 MUg/kg) produced CPP that were statistically significant relative to saline-injected rats. DEX-induced CPP was significantly reversed by pretreatment with naloxone, an opioid antagonist. Naloxone alone treatment did not cause any significant effect on CPP. Our results suggest that DEX produces CPP effects similar to morphine in rats and that opioidergic mechanism may be responsible for DEX-induced CPP. Thus, DEX might have the potential to be addictive, and this possibility should be considered during clinical application of this drug. PMID- 26376285 TI - Emotional contrast or compensation? How support reminders influence the pain of acute peer disapproval in preadolescents. AB - When children experience habitual peer difficulties, adults often remind them that many people care about them. How do such reminders of support impact children's emotional responses to acute experiences of peer disapproval? Intuitively, support reminders would exert compensatory effects attenuating the emotional impact of acute disapproval. Theory suggests, however, that support reminders might also lead to contrast effects magnifying the emotional impact of acute disapproval, especially among socially vulnerable children. These opposing perspectives were pitted against each other. In 2 experiments, children (aged 9 13, M(age) = 11.5) were randomly assigned to reflect on their relationships with either supportive others (support condition) or mere acquaintances (control condition). Children experienced acute peer disapproval immediately after (Experiment 1) or before (Experiment 2) the manipulated support reminder. Among children who experienced higher levels of peer difficulties in their daily life, the support reminder increased externalized emotional reactivity and decreased internalized emotional recovery following disapproval. Thus, consistent with emotional contrast theory, support reminders magnified the disapproval-based emotional responses of socially vulnerable children. PMID- 26376286 TI - Change and predictors of change in parental self-efficacy from early to middle adolescence. AB - Parental self-efficacy (PSE) describes parents' beliefs about being able to handle developmentally specific issues and being able to influence their child in a way that fosters the child's positive development and adjustment (Bandura, 1997). Parents of adolescents have been shown to feel less efficacious than parents of preadolescent children (Ballenski & Cook, 1982), but little is known about the factors behind low levels of PSE among parents of adolescents. This study examined mean-level changes in PSE and predictors of change among parents of adolescents. The sample was derived from a 3-wave longitudinal data set of 398 parents of children starting spanning early (11 or 12 years) to middle (14 or 15 years) adolescence (47% boys). Latent growth curve analysis was performed, and it was hypothesized that theoretically driven predictors reflecting the developing child, as well as the ecological context, would predict the level of PSE. Despite generally high levels of PSE across all time points, parents decreased in PSE during the developmental period. Some predictors were of particular importance for the level and amount of change in PSE, such as physical changes in the child, parents' target-based expectations for risk taking during adolescence, the quality of parent-adolescent communication, and ethnicity. This study adds insight into the development of PSE during the critical transitional period of early and middle adolescence. The findings advance theory of PSE, as it illuminates why some parents' decrease in PSE more than do other parents. PMID- 26376287 TI - Adolescents' use of sexually explicit Internet material and their sexual attitudes and behavior: Parallel development and directional effects. AB - Although research has repeatedly demonstrated that adolescents' use of sexually explicit Internet material (SEIM) is related to their endorsement of permissive sexual attitudes and their experience with sexual behavior, it is not clear how linkages between these constructs unfold over time. This study combined 2 types of longitudinal modeling, mean-level development and cross-lagged panel modeling, to examine (a) developmental patterns in adolescents' SEIM use, permissive sexual attitudes, and experience with sexual behavior, as well as whether these developments are related; and (b) longitudinal directionality of associations between SEIM use on the 1 hand and permissive sexual attitudes and sexual behavior on the other hand. We used 4-wave longitudinal data from 1,132 7th through 10th grade Dutch adolescents (M(age) T1 = 13.95; 52.7% boys) and estimated multigroup models to test for moderation by gender. Mean-level developmental trajectories showed that boys occasionally and increasingly used SEIM over the 18-month study period, which co-occurred with increases in their permissive attitudes and their experience with sexual behavior. Cross-lagged panel models revealed unidirectional effects from boys' SEIM use on their subsequent endorsement of permissive attitudes, but no consistent directional effects between their SEIM use and sexual behavior. Girls showed a similar pattern of increases in experience with sexual behavior, but their SEIM use was consistently low and their endorsement of permissive sexual attitudes decreased over the 18-month study period. In contrast to boys, girls' SEIM use was not longitudinally related to their sexual attitudes and behavior. Theoretical and practical implications of these gender-specific findings are discussed. (PsycINFO Database Record PMID- 26376288 TI - Context-inappropriate anger, emotion knowledge deficits, and negative social experiences in preschool. AB - This study examined contextually inappropriate (CI) anger in relation to emotion recognition and situation knowledge, negative social experiences, and externalizing behavior among low-income 4-year-olds attending Head Start (n = 134). Approximately 23% showed anger when presented with positive/neutral slides and videos (valence-incongruent CI anger), whereas 40% of children showed anger when presented with negative slides and videos (valence-congruent CI anger). Valence-incongruent CI anger was associated with lower emotion situation knowledge (for boys only), more self-reported peer rejection and loneliness, and greater negative nominations by teachers and peers. Both valence-incongruent and (for boys only) valence-congruent CI anger were positively associated with externalizing behavior. Overall, valence-incongruent CI anger was more strongly associated with negative child outcomes than valence-congruent CI anger. PMID- 26376289 TI - Children's attentional exploration of threatening information as related to trust in maternal support. AB - There is increasing interest in attachment-related social information processing, including children's attentional processing of information regarding the attachment figure. Previous research in middle childhood revealed evidence for a stronger attentional focus toward mother in children with less secure attachment expectations. However, the implication of this attentional focus for children's exploration has not been explored. This study tested the hypothesis that this attentional focus toward mother occurs at the expense of attentional exploration of the environment. Ninety children, aged 8-12, completed questionnaires assessing trust in maternal support, watched a video that induced mild fear of dogs, and completed a dot probe computer task assessing attentional processing of simultaneously presented pictures of mother and pictures of the threatening stimulus (i.e., dogs). Less trust in maternal support was linked to a stronger attentional focus toward the mother pictures versus the dog pictures. These results suggest that, in the presence of mother, children with more secure attachment expectations are better able to freely explore a mildly threatening environment. PMID- 26376290 TI - Self-assembly of 33-mer gliadin peptide oligomers. AB - The 33-mer gliadin peptide, LQLQPF(PQPQLPY)3PQPQPF, is a highly immunogenic peptide involved in celiac disease and probably in other immunopathologies associated with gliadin. Herein, dynamic light scattering measurements showed that 33-mer, in the micromolar concentration range, forms polydisperse nano- and micrometer range particles in aqueous media. This behaviour is reminiscent of classical association of colloids and we hypothesized that the 33-mer peptide self-assembles into micelles that could be the precursors of 33-mer oligomers in water. Deposition of 33-mer peptide aqueous solution on bare mica generated nano- and microstructures with different morphologies as revealed by atomic force microscopy. At 6 MUM, the 33-mer is organised in isolated and clusters of spherical nanostructures. In the 60 to 250 MUM concentration range, the spherical oligomers associated mainly in linear and annular arrangements and structures adopting a "sheet" type morphology appeared. At higher concentrations (610 MUM), mainly filaments and plaques immersed in a background of nanospherical structures were detected. The occurrence of different morphologies of oligomers and finally the filaments suggests that the unique specific geometry of the 33-mer oligomers has a crucial role in the subsequent condensation and organization of their fractal structures into the final filaments. The self-assembly process on mica is described qualitatively and quantitatively by a fractal diffusion limited aggregation (DLA) behaviour with the fractal dimension in the range of 1.62 +/- 0.02 to 1.73 +/- 0.03. Secondary structure evaluation of the oligomers by Attenuated Total Reflection FTIR spectroscopy (ATR-FTIR) revealed the existence of a conformational equilibrium of self-assembled structures, from an extended conformation to a more folded parallel beta elongated structures. Altogether, these findings provide structural and morphological information about supramolecular organization of the 33-mer peptide, which might offer new perspectives for the understanding and treatment of gliadin intolerance disorders. PMID- 26376291 TI - Hemodialysis Using High Cut Off Filters in Light Chain Cast Nephropathy. AB - BACKGROUND/AIM: Hemodialysis using high cutoff (HCO) filters possibly improves renal function in diseases with light chain (LC) overproduction and acute kidney injury. We established the effect of HCO dialysis on renal outcome in consecutive patients with malignant monoclonal gammopathies and LC cast nephropathy. METHODS: LC concentration was measured before and after each dialysis session in 10 patients receiving HCO dialysis and bortezomib-based chemotherapy, and their renal function was monitored by plasma creatinine. RESULTS: The number of HCO sessions ranged from 4 to 34 (mean 13). Six patients recovered kidney function, 3 regained partial function while 1 patient continued chronic dialysis. Patients with the largest reductions in LC during HCO treatments had the lowest creatinine at 6 and 9 months of follow-up. For comparison, only 2 out of 10 patients in a historic control group recovered kidney function. CONCLUSION: HCO dialysis combined with bortezomib results in good renal recovery with kidney function being dependent on the degree of LC lowering. PMID- 26376292 TI - Prognostic value of BRAF and KRAS mutation status in stage II and III microsatellite instable colon cancers. AB - Microsatellite instability (MSI) has been associated with favourable survival in early stage colorectal cancer (CRC) compared to microsatellite stable (MSS) CRC. The BRAF V600E mutation has been associated with worse survival in MSS CRC. This mutation occurs in 40% of MSI CRC and it is unclear whether it confers worse survival in this setting. The prognostic value of KRAS mutations in both MSS and MSI CRC remains unclear. We examined the effect of BRAF and KRAS mutations on survival in stage II and III MSI colon cancer patients. BRAF exon 15 and KRAS exon 2-3 mutation status was assessed in 143 stage II (n = 85) and III (n = 58) MSI colon cancers by high resolution melting analysis and sequencing. The relation between mutation status and cancer-specific (CSS) and overall survival (OS) was analyzed using Kaplan-Meier and Cox regression analysis. BRAF V600E mutations were observed in 51% (n = 73) and KRAS mutations in 16% of cases (n = 23). Patients with double wild-type cancers (dWT; i.e., BRAF and KRAS wild-type) had a highly favourable survival with 5-year CSS of 93% (95% CI 84-100%), while patients with cancers harbouring mutations in either BRAF or KRAS, had 5-year CSS of 76% (95% CI 67-85%). In the subgroup of stage II patients with dWT cancers no cancer-specific deaths were observed. On multivariate analysis, mutation in either BRAF or KRAS vs. dWT remained significantly prognostic. Mutations in BRAF as well as KRAS should be analyzed when considering these genes as prognostic markers in MSI colon cancers. PMID- 26376293 TI - Angiotensin II Moderately Decreases Plasmodium Infection and Experimental Cerebral Malaria in Mice. AB - Angiotensin II, a peptide hormone that regulates blood pressure, has been proposed as a protective factor against cerebral malaria based on a genetic analysis. In vitro studies have documented an inhibitory effect of angiotensin II on Plasmodium growth, while studies using chemical inhibitors of angiotensin II in mice showed protection against experimental cerebral malaria but not major effects on parasite growth. To determine whether the level of angiotensin II affects Plasmodium growth and/or disease outcome in malaria, elevated levels of angiotensin II were induced in mice by intradermal implantation of osmotic mini pumps providing constant release of this hormone. Mice were then infected with P. berghei and monitored for parasitemia and incidence of cerebral malaria. Mice infused with angiotensin II showed decreased parasitemia seven days after infection. The development of experimental cerebral malaria was delayed and a moderate increase in survival was observed in mice with elevated angiotensin II, as confirmed by decreased number of cerebral hemorrhages compared to controls. The results presented here show for the first time the effect of elevated levels of angiotensin II in an in vivo model of malaria. The decreased pathogenesis observed in mice complements a previous human genetic study, reinforcing the hypothesis of a beneficial effect of angiotensin II in malaria. PMID- 26376294 TI - Limpet Shells from the Aterian Level 8 of El Harhoura 2 Cave (Temara, Morocco): Preservation State of Crossed-Foliated Layers. AB - The exploitation of mollusks by the first anatomically modern humans is a central question for archaeologists. This paper focuses on level 8 (dated around ~ 100 ka BP) of El Harhoura 2 Cave, located along the coastline in the Rabat-Temara region (Morocco). The large quantity of Patella sp. shells found in this level highlights questions regarding their origin and preservation. This study presents an estimation of the preservation status of these shells. We focus here on the diagenetic evolution of both the microstructural patterns and organic components of crossed-foliated shell layers, in order to assess the viability of further investigations based on shell layer minor elements, isotopic or biochemical compositions. The results show that the shells seem to be well conserved, with microstructural patterns preserved down to sub-micrometric scales, and that some organic components are still present in situ. But faint taphonomic degradations affecting both mineral and organic components are nonetheless evidenced, such as the disappearance of organic envelopes surrounding crossed-foliated lamellae, combined with a partial recrystallization of the lamellae. Our results provide a solid case-study of the early stages of the diagenetic evolution of crossed foliated shell layers. Moreover, they highlight the fact that extreme caution must be taken before using fossil shells for palaeoenvironmental or geochronological reconstructions. Without thorough investigation, the alteration patterns illustrated here would easily have gone unnoticed. However, these degradations are liable to bias any proxy based on the elemental, isotopic or biochemical composition of the shells. This study also provides significant data concerning human subsistence behavior: the presence of notches and the good preservation state of limpet shells (no dissolution/recrystallization, no bioerosion and no abrasion/fragmentation aspects) would attest that limpets were gathered alive with tools by Middle Palaeolithic (Aterian) populations in North Africa for consumption. PMID- 26376295 TI - Insights from Fragment Hit Binding Assays by Molecular Simulations. AB - Novel bioactive molecules can be rationally designed by growing and linking small fragments. Because fragments are fast and promiscuous, it is common to have contradictory hit results between different experimental screening techniques. Here, we simultaneously determine fragment binding poses, affinities, and kinetics on a focused library of 42 fragments against the serine protease factor Xa using multimillisecond molecular dynamics simulations. We predict experimental poses of 12 over 15 S1 crystal structures, and affinities are recovered for 4 out of 6. A kinetic map of protein cavities is computed in terms of on- and off-rates as well as insights into secondary ligand poses. The results suggest that the approach can be useful to recapitulate discordant fragment screening data. PMID- 26376296 TI - Genuflecting to Hospital Variation in Home Discharge-Reply. PMID- 26376302 TI - Human Acid beta-Glucosidase Inhibition by Carbohydrate Derived Iminosugars: Towards New Pharmacological Chaperones for Gaucher Disease. AB - A collection of carbohydrate-derived iminosugars belonging to three structurally diversified sub-classes (polyhydroxylated pyrrolidines, piperidines, and pyrrolizidines) was evaluated for inhibition of human acid beta-glucosidase (glucocerebrosidase, GCase), the deficient enzyme in Gaucher disease. The synthesis of several new pyrrolidine analogues substituted at the nitrogen or alpha-carbon atom with alkyl chains of different lengths suggested an interpretation of the inhibition data and led to the discovery of two new GCase inhibitors at sub-micromolar concentration. In the piperidine iminosugar series, two N-alkylated derivatives were found to rescue the residual GCase activity in N370S/RecNcil mutated human fibroblasts (among which one up to 1.5-fold). This study provides the starting point for the identification of new compounds in the treatment of Gaucher disease. PMID- 26376303 TI - Protein Synthesis in Sub-Micrometer Water-in-Oil Droplets. AB - Water-in-oil (w/o) emulsions are used as a cellular model because of their unique cell-like architecture. Previous works showed the capability of eukaryotic-cell sized w/o droplets (5-50 MUm) to support protein synthesis efficiently; however data about smaller w/o compartments (<1 MUm) are lacking. This work focuses on the biosynthesis of the enhanced green fluorescent protein (EGFP) inside sub micrometric lecithin-based w/o droplets (0.8-1 MUm) and on its dependence on the compartments' dynamic properties in terms of solute exchange mechanisms. We demonstrated that protein synthesis is strongly affected by the nature of the lipid interface. These findings could be of value and interest for both basic and applied research. PMID- 26376297 TI - Biochemical Characterization of Putative Adenylate Dimethylallyltransferase and Cytokinin Dehydrogenase from Nostoc sp. PCC 7120. AB - Cytokinins, a class of phytohormones, are adenine derivatives common to many different organisms. In plants, these play a crucial role as regulators of plant development and the reaction to abiotic and biotic stress. Key enzymes in the cytokinin synthesis and degradation in modern land plants are the isopentyl transferases and the cytokinin dehydrogenases, respectively. Their encoding genes have been probably introduced into the plant lineage during the primary endosymbiosis. To shed light on the evolution of these proteins, the genes homologous to plant adenylate isopentenyl transferase and cytokinin dehydrogenase were amplified from the genomic DNA of cyanobacterium Nostoc sp. PCC 7120 and expressed in Escherichia coli. The putative isopentenyl transferase was shown to be functional in a biochemical assay. In contrast, no enzymatic activity was detected for the putative cytokinin dehydrogenase, even though the principal domains necessary for its function are present. Several mutant variants, in which conserved amino acids in land plant cytokinin dehydrogenases had been restored, were inactive. A combination of experimental data with phylogenetic analysis indicates that adenylate-type isopentenyl transferases might have evolved several times independently. While the Nostoc genome contains a gene coding for protein with characteristics of cytokinin dehydrogenase, the organism is not able to break down cytokinins in the way shown for land plants. PMID- 26376305 TI - Correction: Group Size Effect on Cooperation in One-Shot Social Dilemmas II: Curvilinear Effect. PMID- 26376304 TI - Effects of Granulocyte-Macrophage Colony-Stimulating (GM-CSF) Factor on Corneal Epithelial Cells in Corneal Wound Healing Model. AB - Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pleiotropic cytokine that activates granulocyte and macrophage cell lineages. It is also known to have an important function in wound healing. This study investigated the effect of GM-CSF in wound healing of human corneal epithelial cells (HCECs). We used human GM-CSF derived from rice cells (rice cell-derived recombinant human GM CSF; rhGM-CSF). An in vitro migration assay was performed to investigate the migration rate of HCECs treated with various concentrations of rhGM-CSF (0.1, 1.0, and 10.0 MUg/ml). MTT assay and flow cytometric analysis were used to evaluate the proliferative effect of rhGM-CSF. The protein level of p38MAPK was analyzed by western blotting. For in vivo analysis, 100 golden Syrian hamsters were divided into four groups, and their corneas were de-epithelialized with alcohol and a blade. The experimental groups were treated with 10, 20, or 50 MUg/ml rhGM-CSF four times daily, and the control group was treated with phosphate-buffered saline. The corneal wound-healing rate was evaluated by fluorescein staining at the initial wounding and 12, 24, 36, and 48 hours after epithelial debridement. rhGM-CSF accelerated corneal epithelial wound healing both in vitro and in vivo. MTT assay and flow cytometric analysis revealed that rhGM-CSF treatment had no effects on HCEC proliferation. Western blot analysis demonstrated that the expression level of phosphorylated p38MAPK increased with rhGM-CSF treatment. These findings indicate that rhGM-CSF enhances corneal wound healing by accelerating cell migration. PMID- 26376306 TI - The Gene Polymorphism of IL-17 G-152A is Associated with Increased Colonization of Streptococcus pneumoniae in Young Finnish Children. AB - BACKGROUND: Streptococcus pneumoniae is a common respiratory pathogen, and up to 50% of children acquire S. pneumoniae in their nasopharynx during the first 12 months of life. The cytokine interleukin-17A (IL-17A) plays an important role in host defense against extracellular bacterial pathogens. We investigated the effect of IL-17 G-152A polymorphism on pneumococcal colonization in children. METHODS: Nasopharyngeal swabs and blood samples were collected from healthy Finnish children at 2.6 (N = 405), 13 (N = 198) and 24 (N = 176) months of age. Of them, 160 had both nasopharyngeal swabs and blood samples at each time point. The semiquantitative culture method was used for bacterial culture, Sequenom iPlex Gold System for IL-17A genotyping and Luminex 200 for serum IL-17A determination. RESULTS: The frequency of IL-17 G-152A genotypes G/G, G/A and A/A was 36%, 45% and 19% in 405 studied subjects, respectively. The colonization rates of S. pneumoniae increased from 10% at 2.6 months to 33% at 24 months of age. Significantly higher pneumococcal colonization was found in subjects with A/A genotype at 13 and 24 months of age compared with those of G/G (RR, 2.30; P = 0.02; RR, 1.91, P = 0.03). This genotype was associated with lower levels of serum IL-17A, and only 6% of subjects with A/A had detectable serum IL-17A compared with 75% and 33% of subjects with G/G and G/A (P < 0.001 and P < 0.01), respectively. CONCLUSIONS: Our results indicate that IL-17 G-152A is associated with increased colonization rate of S. pneumoniae in young children, suggesting that IL-17A plays an important role in protection against pneumococcal colonization. PMID- 26376307 TI - Clinical and Microbiology Profile and Outcome of Diarrhea by Coccidian Parasites in Immunocompetent Children. AB - BACKGROUND: Several studies have reported prevalence of pediatric coccidian parasitic diarrhea, but there is little information about their clinical profile, management and outcome. This study reviews the clinical profile and treatment outcome of coccidian parasitic diarrhea in immunocompetent children. METHODS: Five thousand one hundred and twenty-three immunocompetent children younger than 15 years of age presenting with acute diarrhea to a tertiary care pediatric hospital during a period of 4 years (2009-2012) were included in the study. Their demographic details and clinical course were recorded, and feces specimens received in the microbiology laboratory were subject to microbiology culture, wet mount microscopy, modified Ziehl-Neelsen staining to detect intestinal coccidian parasites and rotavirus sandwich enzyme-linked immunosorbent assay test (if age less than 2 years). RESULTS: The prevalence of coccidian parasitic diarrhea in immunocompetent children was 1.13% (58 cases) with Cryptosporidium spp. accounting for 1.09% (56 cases). Most Cryptosporidium infections were in children younger than 2 years [38 (67.85%)] and during the monsoon season [32 (57.14%)] with common clinical features being watery or liquid feces [44 (78.57%)], vomiting [40 (71.43%)] and fever [35 (62.5%)]. Thirteen (81.25%) of the 16 cases of cryptosporidiosis with dehydration were less than 2 years of age. Fifty-one (87.93%) of the 58 children were hospitalized. Thirty-eight (67.85%) children with cryptosporidiosis received empiric antimicrobial agents for suspected enteric bacterial and protozoan parasitic infection, which were discontinued after coccidian parasites were detected. Median duration of hospitalization was 2 days with no mortality reported. CONCLUSIONS: Coccidian parasitic diarrhea affects immunocompetent children of all age groups. Unnecessary administration of antimicrobial agents to these children can be avoided by routinely screening pediatric diarrheal fecal specimens for coccidian parasites by a cost-effective method such as modified Ziehl-Neelsen staining. PMID- 26376308 TI - Cefepime and Ceftazidime Safety in Hospitalized Infants. AB - BACKGROUND: Cefepime and ceftazidime are cephalosporins used for the treatment of serious Gram-negative infections. These cephalosporins are used off-label in the setting of minimal safety data for young infants. METHODS: We identified all infants discharged from 348 neonatal intensive care units managed by the Pediatrix Medical Group between 1997 and 2012 who were exposed to either cefepime or ceftazidime in the first 120 days of life. We reported clinical and laboratory adverse events occurring in infants exposed to cefepime or ceftazidime and used multivariable logistic regression to compare the odds of seizures and death between the 2 groups. RESULTS: A total of 1761 infants received 13,293 days of ceftazidime, and 594 infants received 4628 days of cefepime. Laboratory adverse events occurred more frequently on days of therapy with ceftazidime than with cefepime (373 vs. 341 per 1000 infant days, P < 0.001). Seizure was the most commonly observed clinical adverse event, occurring in 3% of ceftazidime-treated infants and 4% of cefepime-treated infants (P = 0.52). Mortality was similar between the ceftazidime and cefepime groups (5% vs. 3%, P = 0.07). There was no difference in the adjusted odds of seizure [odds ratio (OR) = 0.96 (95% confidence interval: 0.89-1.03)] or the combined outcome of mortality or seizures [OR = 1.00 (0.96-1.04)] in infants exposed to ceftazidime versus those exposed to cefepime. CONCLUSIONS: In this cohort of infants, cefepime was associated with fewer laboratory adverse events than ceftazidime, although this may have been due to a significant difference in clinical exposures and severity of illness between the 2 groups. There was no difference in seizure risk or mortality between the 2 drugs. PMID- 26376310 TI - Pericardial Effusion and Adenosine Deaminase False Positivity Due to Parvovirus B19. AB - This case is presented to highlight that one of the causes for massive exudative pericardial effusion in a child may be parvovirus B19, and adenosine deaminase can be falsely positive in such patients. PMID- 26376309 TI - Executive Functioning in Children and Adolescents With Perinatal HIV Infection. AB - BACKGROUND: Perinatal HIV (PHIV) infection may place youth at risk for impairments in executive functioning (EF). We examined associations of EF with HIV infection, disease severity and other factors among youth with PHIV and perinatally HIV-exposed, uninfected youth (PHEU). METHODS: Within the US-based Pediatric HIV/AIDS Cohort Study, 354 PHIV and 200 PHEU youth completed a standardized EF measure (Children's Color Trails Test, CCTT) and youth and/or caregivers completed a questionnaire measuring everyday EF (Behavior Rating Inventory of Executive Function, BRIEF). Covariates included HIV status, current and historical disease severity, demographic and caregiver variables and other cognitive measures. Analyses used linear and logistic regression and proportional odds models. RESULTS: No significant HIV status group differences were found on CCTT scores. Caregiver BRIEF ratings indicated significantly fewer problems for PHIV than PHEU youth. However, PHIV youth with past encephalopathy self-endorsed significantly greater metacognitive (ie, cognitive regulation) problems on the BRIEF and performed more slowly on the CCTT than PHEU youth. CCTT and caregiver BRIEF scores had significant associations with indicators of past and present disease severity. Both PHIV and PHEU had significantly worse scores than population means on CCTT and BRIEF; scores had significant associations with demographic covariates. CONCLUSIONS: Youth with PHIV show EF problems likely associated with risk factors other than HIV. However, cognitive slowing and self reported metacognitive problems were evident in PHIV youth with a history of encephalopathy. Assessment and treatment of EF impairment may be important to identifying PHIV youth at particular risk for poor health and behavioral outcomes. PMID- 26376311 TI - Late-onset Group B Streptococcal Meningitis, Potential Effectiveness of a Vaccine by Maternal Immunization? PMID- 26376312 TI - Chronic Infection with Rotavirus Vaccine Strains in UK Children with Severe Combined Immunodeficiency. PMID- 26376313 TI - Advantages of Polymerase Chain Reaction Assay Performed on Gastric Aspirates for Rapid Diagnosis of Pulmonary Tuberculosis in Children in a Low Prevalence Country. PMID- 26376314 TI - Nosocomial Neonatal Listeria monocytogenes Transmission by Stethoscope. PMID- 26376315 TI - Clinical Predictors of Culture-confirmed Pulmonary Tuberculosis in Children in a High Tuberculosis and HIV Prevalence Area. AB - BACKGROUND: The burden of childhood tuberculosis (TB) remains significant especially in areas of high HIV prevalence. Clinical diagnosis predominates, despite advances in molecular and microbiological diagnostics. The aim of this study is to identify clinical features associated with culture-confirmed pulmonary TB (PTB) in children. METHODS: Children admitted to hospital were enrolled in a study of novel diagnostics for PTB in South Africa. Standardized clinical, radiological and microbiological data were collected. Definite TB was defined by culture of Mycobacterium tuberculosis from a respiratory specimen. Adjusted odds ratios for definite TB were calculated using a multivariate logistic regression model. RESULTS: Adjusted odds ratio (AOR) for definite TB increased with a history of fever for more than 1 week [AOR: 8.54, 95% confidence interval (CI): 2.37-30.74], with a chest radiograph (CXR) suggestive of PTB (AOR: 10.0, 95% CI: 3.22-31.2) and with a positive tuberculin skin test (TST; AOR: 64.4, 95% CI: 14.3-290.5). The likelihood ratio of having definite TB if 2 of these factors (CXR and TST) were present compared with having none of them was 17.7. Cough, household contact with TB, HIV status and wheezing were not significantly associated with definite TB. CONCLUSIONS: Prolonged fever, CXR suggestive of TB or a positive TST were predictive of definite TB and should be considered in composite scoring systems for TB diagnosis in high HIV prevalence settings. Other commonly associated symptoms were not associated with definite TB. PMID- 26376316 TI - Pertussis Across the Globe: Recent Epidemiologic Trends From 2000 to 2013. AB - Pertussis has reemerged as a problem across the world. To better understand the nature of the resurgence, we reviewed recent epidemiologic data and we report disease trends from across the world. Published epidemiologic data from January 2000 to July 2013 were obtained via PubMed searches and open-access websites. Data on vaccine coverage and reported pertussis cases from 2000 through 2012 from the 6 World Health Organization regions were also reviewed. Findings are confounded not only by the lack of systematic and comparable observations in many areas of the world but also by the cyclic nature of pertussis with peaks occurring every 3-5 years. It appears that pertussis incidence has increased in school-age children in North America and western Europe, where acellular pertussis vaccines are used, but an increase has also occurred in some countries that use whole-cell vaccines. Worldwide, pertussis remains a serious health concern, especially for infants, who bear the greatest disease burden. Factors that may contribute to the resurgence include lack of booster immunizations, low vaccine coverage, improved diagnostic methods, and genetic changes in the organism. To better understand the epidemiology of pertussis and optimize disease control, it is important to improve surveillance worldwide, irrespective of pertussis vaccine types and schedules used in each country. PMID- 26376318 TI - Clinical Research Abstracts of the British Equine Veterinary Association Congress 2015. AB - REASONS FOR PERFORMING STUDY: Atrial fibrillation is a common equine arrhythmia. Quinidine alone, or with digoxin are common treatments. Studies on outcome in Warmblood populations in which duration of the AF is often unknown are limited. OBJECTIVES: To identify the factors that are associated with the success of full treatment cardioversion with oral medication, and establish whether there are differences in these factors between institutions. STUDY DESIGN: Retrospective case series using patient records of Equine University Clinic of Utrecht University and Rossdales Equine Hospital, Newmarket. METHODS: Forty-nine horses treated with quinidine were identified (29 Warmbloods, 20 Thorougbreds, 1 Anglo Arabian). Details of signalment, history, duration physical examination and echocardiography including left atrial size and presence of mitral regurgitation were retrieved. Clinical details including mean weight, age and left atrial size were compared between clinics using independent samples t test. Association between variables and cardioconversion were evaluated in a backwards logistic regression using Akaike's information criterium (AIC) and odds ratios were calculated. Factors were sex, clinic, breed, mitral regurgitation, duration and poor performance. Covariates were age, weight and the size of the left atrium. Significance was set at 0.05. RESULTS: Fifty-one horses (mean age 8.8 s.d. 4.5 years) were treated with quinidine sulfate, 18 also received digoxin. Eighty per cent converted to sinus rhythm. In 8 horses the known duration was less than 3 months. The only factor associated with successful treatment was the use of digoxin in combination with quinidine sulfate (odds ratio 12.4; 95% CI 2.61 and 91.85 according to AIC analysis). CONCLUSIONS: In this retrospective case series, there is much potential for bias in the data; however, the use of digoxin in addition to quinidine was associated with improved conversion rates regardless of breed even though AF duration was unknown in most horses. Ethical animal research: Research ethics committee oversight not currently required by this conference: retrospective study of clinical records. Explicit owner informed consent for inclusion of animals in this study was not stated. SOURCE OF FUNDING: None. Competing interests: None declared. PMID- 26376317 TI - A Foodborne Outbreak of Gastroenteritis Caused by Vibrio parahaemolyticus and Norovirus through Non-Seafood Vehicle. AB - Foodborne outbreaks caused by a mixed infection of Vibrio parahaemolyticus and norovirus have rarely been described. We reported a mixed outbreak of Vibrio parahaemolyticus and norovirus causing acute gastroenteritis in 99 staff members of a company in Guangdong, China, in May 2013, following consumption of roasted duck, an uncommon non-seafood vehicle for such mixed infection, in one meal served in the company's catering service. Epidemiological and laboratory findings indicated that a single asymptomatic food handler was the source of both pathogens, and the high rate of infection of both pathogens was exacerbated by the setting's suboptimal food hygiene practice. PMID- 26376319 TI - Synthesis of Novel Nucleoside Analogues Built on a Bicyclo[4.1.0]heptane Scaffold. AB - A new class of carbocyclic nucleoside analogues built on a bicyclo[4.1.0]heptane scaffold, a perspective novel pseudosugar pattern, have been conceived as anti HSV agents on the basis of initial protein-ligand docking studies. The asymmetric synthesis of a series of these compounds incorporating different nucleobases has been efficiently completed starting from 1,4-cyclohexanedione. PMID- 26376320 TI - A Comprehensive Analysis in Terms of Molecule-Intrinsic, Quasi-Atomic Orbitals. II. Strongly Correlated MCSCF Wave Functions. AB - A methodology is developed for the quantitative identification of the quasi atomic orbitals that are embedded in a strongly correlated molecular wave function. The wave function is presumed to be generated from configurations in an internal orbital space whose dimension is equal to (or slightly larger) than that of the molecular minimal basis set. The quasi-atomic orbitals are found to have large overlaps with corresponding orbitals on the free atoms. They separate into bonding and nonbonding orbitals. From the bonding quasi-atomic orbitals, localized bonding and antibonding molecular orbitals are formed. The resolution of molecular density matrices in terms of these orbitals furnishes a basis for analyzing the interatomic bonding patterns in molecules and the changes in these bonding patterns along reaction paths. A new bond strength measure, the kinetic bond order, is introduced. PMID- 26376321 TI - Insights into the Social Structure of the PPNB Site of Kfar HaHoresh, Israel, Based on Dental Remains. AB - One of the central questions of the transition from mobile hunter-gatherers to sedentary farming communities concerns the establishment of new social structures and group identities. Along with other important factors, such as territory, ideology or economy, biological relationships might have played a decisive role in defining social groups. We therefore systematically analyzed teeth and jaw remains from nine sites in the Near East dating from the Natufian to the Late PPNB as primary proxy data for the reconstruction of familial relationships. This paper presents the results of morphological analyses on the teeth of the individuals from Kfar HaHoresh, one of the investigated Pre-Pottery Neolithic B sites. Kfar HaHoresh is located in the Nazareth hills of Galilee (32 degrees 42'20'' N 35 degrees 16'28'' E), Israel. Different statistical methods were applied to our data of epigenetic traits with the aim of determining biological relationships within the community, whereby the data of the eight other sites were used as cross-references. Our comparison of the traits of all individuals from Kfar HaHoresh indicates a rather heterogeneous community, but clearly shows one cluster belonging to a quite homogenous group, suggesting close biological relations between females and sub-adults. Interestingly, none of the male individuals belongs to this cluster, although their number outweighs that of the female individuals. This might suggest matrilocal residence patterns. However, due to the incomplete preservation of the teeth along with several other uncertainties, our conclusion must be seen as preliminary. A cross-examination of the results on skeletons excavated after our investigation should also be taken into consideration. PMID- 26376322 TI - Future development of gastrointestinal cancer incidence and mortality rates in Switzerland: a tumour registry- and population-based projection up to 2030. AB - QUESTIONS UNDER STUDY: Since tumour burden consumes substantial healthcare resources, precise cancer incidence estimations are pivotal to define future needs of national healthcare. This study aimed to estimate incidence and mortality rates of oesophageal, gastric, pancreatic, hepatic and colorectal cancers up to 2030 in Switzerland. METHODS: Swiss Statistics provides national incidences and mortality rates of various cancers, and models of future developments of the Swiss population. Cancer incidences and mortality rates from 1985 to 2009 were analysed to estimate trends and to predict incidence and mortality rates up to 2029. Linear regressions and Joinpoint analyses were performed to estimate the future trends of incidences and mortality rates. RESULTS: Crude incidences of oesophageal, pancreas, liver and colorectal cancers have steadily increased since 1985, and will continue to increase. Gastric cancer incidence and mortality rates reveal an ongoing decrease. Pancreatic and liver cancer crude mortality rates will keep increasing, whereas colorectal cancer mortality on the contrary will fall. Mortality from oesophageal cancer will plateau or minimally increase. If we consider European population-standardised incidence rates, oesophageal, pancreatic and colorectal cancer incidences are steady. Gastric cancers are diminishing and liver cancers will follow an increasing trend. Standardised mortality rates show a diminution for all but liver cancer. CONCLUSIONS: The oncological burden of gastrointestinal cancer will significantly increase in Switzerland during the next two decades. The crude mortality rates globally show an ongoing increase except for gastric and colorectal cancers. Enlarged healthcare resources to take care of these complex patient groups properly will be needed. PMID- 26376323 TI - Clinical Research Abstracts of the British Equine Veterinary Association Congress 2015. AB - REASONS FOR PERFORMING STUDY: Infiltrative disease of the intestine is an important cause of weight loss in the horse. Infiltration of inflammatory or neoplastic cells into the intestinal wall and intestinal fibrosis cause changes in the integrity of the intestinal wall. This may lead to altered intestinal permeability which can be measured using the contrast medium iohexol. OBJECTIVES: To determine if iohexol intestinal permeability, as evaluated by serum iohexol concentration, could be used to differentiate between healthy horses and horses with infiltrative disease of the large colon. STUDY DESIGN: Prospective non randomised controlled clinical trial. METHODS: Six healthy adult horses and 4 horses with chronic infiltrative disease of the large colon were used in the study. Infiltrative disease was confirmed on post mortem in all cases, and included alimentary lymphoma and mycobacterial granulomatous enterocolitis. Following a 16-h fast, each horse was dosed with 1.0 ml/kg bwt of iohexol as a 10% solution via nasogastric intubation. Blood samples were collected at 0, 30, 60, 120, 180, 240, 300, 360, 420 and 480 min after dosing. Iohexol concentration was determined using HPLC-UV and the differences between the groups were analysed with a repeated measures ANOVA. RESULTS: There was a statistically significant difference in iohexol serum concentration between the diseased and nondiseased horses (P = 0.001). The overall difference in the mean iohexol concentration between the 2 groups was 6.07 (95% CI 3.19-8.96) MUg/ml, however there appeared to be a trend towards increasing difference at later time points (240, 300, 360 min). CONCLUSIONS: The iohexol permeability test has potential as a diagnostic tool for estimation of intestinal permeability in horses with infiltrative intestinal disease. Further studies are warranted to determine whether the test can be used to determine the site of intestinal pathology, predict the prognosis and potentially evaluate the response to treatment. ACKNOWLEDGEMENTS: The authors thank Professor Riitta-Mari Tulamo and Professor Thomas Spillmann and the staff of Equine College Ypaja and the University of Helsinki Equine Teaching Hospital. The cooperation of horse owners is gratefully acknowledged. Ethical animal research: The study protocol was approved by the National Animal Experiment Board of Finland (Elainkoelautakunta ELLA, Request for Animal Experiments, ref. no. ESAVI-2010-06567/Ym-23). For client-owned animals, owner informed consent was obtained. SOURCE OF FUNDING: This study was funded by the Faculty of Veterinary Medicine, University of Helsinki, Finland. Competing interests: None declared. PMID- 26376326 TI - Deciphering Photoluminescence Dynamics and Reactivity of the Luminescent Metal Metal-Bonded Excited State of a Binuclear Gold(I) Phosphine Complex Containing Open Coordination Sites. AB - Luminescent metal complexes having open coordination sites hold promise in the design of sensory materials and photocatalysts. As a prototype example, [Au2 (dcpm)2)](2+) (dcpm = bis(dicyclohexylphosphanyl) is known for its intriguing environmental sensitive photoluminescence. By integrating a range of complementary ultrafast time-resolved spectroscopy to interrogate the excited state dynamics, this study uncovers that the events occurring in extremely rapid timescales and which are modulated strongly by environmental conditions play a pivotal role in the luminescence behavior and photochemical outcomes. Formed independent of the phase and solvent property within ~0.15 ps, the metal-metal bonded (3)5dsigma*6psigma state is highly reactive possessing strong propensity toward increasing coordination number at Au(I) center, and with ~510 ps lifetime in dichloromethane is able to mediate light induced C-X bond cleavage. PMID- 26376327 TI - Intramolecular Acylal Cyclisation (IAC) as an Efficient Synthetic Strategy towards the Total Synthesis of Erythrina Alkaloid Derivatives. AB - Compounds that comprise the erythrina alkaloid class of natural products are based on a tetracyclic spiroamine framework and exhibit a range of biological activities on the central nervous system. Herein, we report a new and efficient total synthesis of this multiple-ring system based on an intramolecular acylal cyclisation (IAC) approach. Using this methodology, the tetracyclic core was rapidly assembled over a two-step domino process catalysed by a Lewis acid. The effect of heteroatoms, substituents and ring size on the IAC has also been investigated, and the broad application of this procedure is demonstrated by the synthesis of a library of derivatives in good yields with excellent regioselectivity. PMID- 26376328 TI - Organosulfide-Catalyzed Diboration of Terminal Alkynes under Light. AB - An efficient metal-free diboration of terminal alkynes is reported. In the presence of a catalytic amount of organosulfides under light, the addition of bis(pinacolato)diboron (B2pin2) to terminal alkynes takes place efficiently to produce the corresponding double borylation products in good yields. Mechanistic studies indicate that this metal-free sulfide-catalyzed diboration of alkynes likely occurs by generation of a boryl-centered radical with the aid of light and a sulfide, since such a radical was detected in the reaction mixture by electron spin resonance (ESR) spectroscopy. The present form of catalysis (sulfide/light) is thought to be unprecedented and provides a new means of preparation for organoboranes without heavy metal contamination in the products, which is highly desired in the preparation of drugs and electronic materials. PMID- 26376329 TI - Gd-DTPA-Dopamine-Bisphytanyl Amphiphile: Synthesis, Characterisation and Relaxation Parameters of the Nanoassemblies and Their Potential as MRI Contrast Agents. AB - Here, a new amphiphilic magnetic resonance imaging (MRI) contrast agent, a Gd(III)-chelated diethylenetriaminepentaacetic acid conjugated to two branched alkyl chains via a dopamine spacer, Gd-DTPA-dopamine-bisphytanyl (Gd-DTPA-Dop Phy), which is readily capable of self-assembling into liposomal nanoassemblies upon dispersion in an aqueous solution, is reported. In vitro relaxivities of the dispersions were found to be much higher than Magnevist, a commercially available contrast agent, at 0.47 T but comparable at 9.40 T. Analysis of variable temperature (17)O NMR transverse relaxation measurements revealed the water exchange of the nanoassemblies to be faster than that previously reported for paramagnetic liposomes. Molecular reorientation dynamics were probed by (1)H NMRD profiles using a classical inner and outer sphere relaxation model and a Lipari Szabo "model-free" approach. High payloads of Gd(III) ions in the liposomal nanoassemblies made solely from the Gd-DTPA-Dop-Phy amphiphiles, in combination with slow molecular reorientation and fast water exchange makes this novel amphiphile a suitable candidate to be investigated as an advanced MRI contrast agent. PMID- 26376330 TI - Bamboo-Like Nitrogen-Doped Carbon Nanotubes with Co Nanoparticles Encapsulated at the Tips: Uniform and Large-Scale Synthesis and High-Performance Electrocatalysts for Oxygen Reduction. AB - In recent years, various non-precious metal electrocatalysts for the oxygen reduction reaction (ORR) have been extensively investigated. The development of an efficient and simple method to synthesize non-precious metal catalysts with ORR activity superior to that of Pt is extremely significant for large-scale applications of fuel cells. Here, we develop a facile, low-cost, and large-scale synthesis method for uniform nitrogen-doped (N-doped) bamboo-like CNTs (NBCNT) with Co nanoparticles encapsulated at the tips by annealing a mixture of cobalt acetate and melamine. The uniform NBCNT shows better ORR catalytic activity and higher stability in alkaline solutions as compared with commercial Pt/C and comparable catalytic activity to Pt/C in acidic media. NBCNTs exhibit outstanding ORR catalytic activity due to high defect density, uniform bamboo-like structure, and the synergistic effect between the Co nanoparticles and protective graphitic layers. This facile method to synthesize catalysts, which is amenable to the large-scale commercialization of fuel cells, will open a new avenue for the development of low-cost and high-performance ORR catalysts to replace Pt-based catalysts for applications in energy conversion. PMID- 26376331 TI - Short Access to Belt Compounds with Spatially Close C=C Bonds and Their Transannular Reactions. AB - Two domino Diels-Alder adducts were obtained from 3,7-bis(cyclopenta-2,4-dien-1 ylidene)-cis-bicyclo[3.3.0]octane and dimethyl acetylenedicarboxylate or N methylmaleimide under microwave irradiation. From the first adduct, a C20H24 diene with C2v symmetry was obtained by Zn/AcOH reduction, hydrolysis, oxidative decarboxylation, and selective hydrogenation. Photochemical [2+2] cycloaddition of this diene gave a thermally unstable cyclobutane derivative, which reverts to the diene. However, both the diene and the cyclobutane derivatives could be identified by X-ray diffraction analysis upon irradiation of the diene crystal. New six-membered rings are formed upon the transannular addition of bromine or iodine to the diene. The N-type selectivity of the addition was examined by theoretical calculations, which revealed the distinct susceptibility of the doubly bonded carbon atoms to the bromine attack. PMID- 26376332 TI - Initiation Chemistries in Hydrocarbon (Aut)Oxidation. AB - For the (aut)oxidation of toluene to benzyl hydroperoxide, benzyl alcohol, benzaldehyde, and benzoic acid, the thermochemical profiles for various radical generating reactions have been compared. A key intermediate in all of these reactions is benzyl hydroperoxide, the heat of formation of which has been estimated by using results from CBS-QB3, G4, and G3B3 calculations. Homolytic O-O bond cleavage in this hydroperoxide is strongly endothermic and thus unlikely to contribute significantly to initiation processes. In terms of reaction enthalpies the most favorable initiation process involves bimolecular reaction of benzyl hydroperoxide to yield hydroxy and benzyloxy radicals along with water and benzaldehyde. The reaction enthalpy and free energy of this process is significantly more favorable than those for the unimolecular dissociation of known radical initiators, such as dibenzoylperoxide or dibenzylhyponitrite. PMID- 26376333 TI - Palladium-Catalyzed Oxidative Cross-Coupling of alpha-Cyanoketene Dithioacetals with Olefins. AB - Efficient palladium-catalyzed cross-coupling reactions of the internal olefins alpha-cyanoketene dithioacetals with a variety of olefins were achieved in dioxane/HOAc/DMSO (9:3:1 v/v/v) under air atmosphere or by means of AgOAc as the terminal oxidant. Electron-deficient terminal olefins reacted to form the linear diene derivatives with air as the oxidant. Styrenes underwent the cross-coupling to give both the linear and branched dienes when using AgOAc as the oxidant. Unactivated cyclic and linear internal olefin substrates both reacted in the presence of a catalytic amount of benzoquinone in air to produce skipped dienes. The typical products were structurally confirmed by X-ray crystallography. PMID- 26376337 TI - SSZ-13 Crystallization by Particle Attachment and Deterministic Pathways to Crystal Size Control. AB - Many synthetic and natural crystalline materials are either known or postulated to grow via nonclassical pathways involving the initial self-assembly of precursors that serve as putative growth units for crystallization. Elucidating the pathway(s) by which precursors attach to crystal surfaces and structurally rearrange (postattachment) to incorporate into the underlying crystalline lattice is an active and expanding area of research comprising many unanswered fundamental questions. Here, we examine the crystallization of SSZ-13, which is an aluminosilicate zeolite that possesses exceptional physicochemical properties for applications in separations and catalysis (e.g., methanol upgrading to chemicals and the environmental remediation of NO(x)). We show that SSZ-13 grows by two concerted mechanisms: nonclassical growth involving the attachment of amorphous aluminosilicate particles to crystal surfaces and classical layer-by layer growth via the incorporation of molecules to advancing steps on the crystal surface. A facile, commercially viable method of tailoring SSZ-13 crystal size and morphology is introduced wherein growth modifiers are used to mediate precursor aggregation and attachment to crystal surfaces. We demonstrate that small quantities of polymers can be used to tune crystal size over 3 orders of magnitude (0.1-20 MUm), alter crystal shape, and introduce mesoporosity. Given the ubiquitous presence of amorphous precursors in a wide variety of microporous crystals, insight of the SSZ-13 growth mechanism may prove to be broadly applicable to other materials. Moreover, the ability to selectively tailor the physical properties of SSZ-13 crystals through molecular design offers new routes to optimize their performance in a wide range of commercial applications. PMID- 26376336 TI - Older Age as a Prognostic Factor of Attenuated Pain Recovery After Shoulder Arthroscopy. AB - BACKGROUND: Shoulder pain and surgery are common among older adults. However, the extent to which older age affects recovery after shoulder surgery is not well understood. OBJECTIVE: To assess influence of older age on postoperative recovery factors 3 and 6 months after shoulder arthroscopy. DESIGN: Prospective cohort study. SETTING: University-affiliated outpatient orthopedic surgical center. PATIENTS: A convenience sample of 139 persons between 20 and 79 years of age who experienced shoulder pain, had musculoskeletal dysfunction based on imaging and physician assessment, and were scheduled for an arthroscopic shoulder procedure. MAIN OUTCOME MEASURES: Postoperative outcomes were compared among younger, middle aged, and older adults before surgery and at 3 and 6 months after surgery using analysis of variance modeling. Movement-evoked pain and an experimental laboratory correlate of pain processing were assessed at each time point. The influence of older age on 3- and 6-month pain outcomes were determined via multivariate regression analyses after accounting for preoperative, intraoperative, and postoperative prognostic factors. RESULTS: Older adults had higher movement-evoked pain intensity (F2,108 = 5.18, P = .007) and experimental pain response (F2,111 = 7.24, P = .001) at 3 months compared with young and middle-aged adults. After controlling for key prognostic factors, older age remained a positive predictor of 3-month movement-evoked pain (R(2) = 0.05; standardized [St.] beta = 0.263, P = .031) and experimental pain response (R(2) = 0.07; St. beta = 0.295, P = .014). Further, older age remained a positive predictor of movement-evoked pain at 6 months (R(2) = 0.04; St. beta = 0.231, P = .004), despite no age group differences in outcome. Older age was found to be the strongest predictor of 3- and 6-month movement-evoked pain. CONCLUSION: Older adults may experience more pain related to movement, as well as endogenous pain excitation, in the first few months after shoulder arthroscopy. Future age related research should consider use of movement-evoked pain intensity and experimental pain response as pain outcomes, as well as the utility of such measures in clinical care. PMID- 26376338 TI - Mandibular Denture Base Deformation with Locator and Ball Attachments of Implant Retained Overdentures. AB - PURPOSE: The aim of this in vitro study was to evaluate and compare mandibular denture base deformation between ball and Locator attachments of implant-retained overdentures. MATERIALS AND METHODS: An experimental acrylic model covered with resilient silicone mucosal simulation was constructed. Two laboratory implants were placed in the canine areas of the model. Two duplicate experimental overdentures were constructed and connected to the implants with either ball (GI) or Locator (GII) attachments. To measure overdenture strain around the attachments, 3 strain gauges were attached to the lingual polished surface of the overdentures opposite to the right implant (loading side) 2 mm above the attachment level (Ch1), at the attachment level (Ch2), and 2 mm below the attachment level (Ch3). Another 3 gauges were bonded opposite to the left implant (non-loading side) in the same manner (Ch6, Ch7, and Ch8). To measure strain at the midline of the overdentures, two strain gauges were attached in the midline at 5 mm intervals (Ch4 and Ch5). A universal testing device was used to deliver vertical static load of 50 N unilaterally and bilaterally to the first molar area to measure strain using a multi-channel digital strain meter. RESULTS: During bilateral load application, GII recorded higher compressive strains than GI at the majority of channels. During unilateral load application, GI recorded higher tensile strains at Ch1, Ch2, and Ch3, and GII recorded higher strains than GI at Ch6, Ch7, and Ch8. During bilateral loading the highest strain was concentrated at Ch5 for both groups. During unilateral loading, the highest strain was concentrated at Ch2 for GI, and at Ch5 for GII. CONCLUSION: Ball attachments for implant-retained overdentures were associated with significant mandibular denture base deformation over the implants compared to Locator attachments. Therefore, denture base reinforcement may be recommended with ball attachmentz to increase fracture resistance of the base. PMID- 26376339 TI - Ultrastructural evaluation of enamel surface morphology after tooth bleaching followed by the application of protective pastes. AB - The aim of the present in vitro study was to evaluate the morphology of bleached enamel surface followed by the application of different protective pastes. Specimens were prepared from 50 human incisors free of caries and defects. The bleaching procedure was performed with 35% hydrogen peroxide (Perfect Bleach Office+). For the remineralization treatment, different protective pastes (Tooth Mousse, MI Paste Plus, Remin Pro, and Profluorid Varnish) were evaluated. Specimens were randomly assigned to 10 groups of 5 specimens each. The specimens were analyzed under scanning electron microscopy. The superficial morphology of enamel was examined and scored as follows: 0, enamel with smooth surface morphology; 1, enamel with slight irregularities; 2, enamel with moderate irregularities; 3, enamel with accentuated irregularities. The photomicrographs were evaluated in a double-blind manner by three examiners, previously calibrated. Results were analyzed by a Kruskal-Wallis nonparametric test, at the significance level of 0.05. Dunn method posttest was applied for multiple comparisons. A different superficial morphology was observed among control group specimens and specimens treated with bleaching agent and protective pastes (p < 0.05). Enamel bleached showed pronounced surface changes and irregularities, significantly different from other groups except for groups 8 (enamel + Perfect Bleach Office+ + Remin Pro) and 10 (enamel + Perfect Bleach Office+ + Profluorid Varnish) (p > 0.05). The application of the tested pastes after bleaching is effective on repairing enamel surface morphology, demonstrating a higher efficacy for the CPP-ACP products compared to fluoridated ones. SCANNING 38:221-226, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26376340 TI - A Glaucoma-Associated Variant of Optineurin, M98K, Activates Tbk1 to Enhance Autophagosome Formation and Retinal Cell Death Dependent on Ser177 Phosphorylation of Optineurin. AB - Certain missense mutations in optineurin/OPTN and amplification of TBK1 are associated with normal tension glaucoma. A glaucoma-associated variant of OPTN, M98K, induces autophagic degradation of transferrin receptor (TFRC) and death in retinal cells. Here, we have explored the role of Tbk1 in M98K-OPTN-induced autophagy and cell death, and the effect of Tbk1 overexpression in retinal cells. Cell death induced by M98K-OPTN was dependent on Tbk1 as seen by the effect of Tbk1 knockdown and blocking of Tbk1 activity by a chemical inhibitor. Inhibition of Tbk1 also restores M98K-OPTN-induced transferrin receptor degradation. M98K OPTN-induced autophagosome formation, autophagy and cell death were dependent on its phosphorylation at S177 by Tbk1. Knockdown of OPTN reduced starvation-induced autophagosome formation. M98K-OPTN expressing cells showed higher levels of Tbk1 activation and enhanced phosphorylation at Ser177 compared to WT-OPTN expressing cells. M98K-OPTN-induced activation of Tbk1 and its ability to be phosphorylated better by Tbk1 was dependent on ubiquitin binding. Phosphorylated M98K-OPTN localized specifically to autophagosomes and endogenous Tbk1 showed increased localization to autophagosomes in M98K-OPTN expressing cells. Overexpression of Tbk1 induced cell death and caspase-3 activation that were dependent on its catalytic activity. Tbk1-induced cell death possibly involves autophagy, as shown by the effect of Atg5 knockdown, and requirement of autophagic function of OPTN. Our results show that phosphorylation of Ser177 plays a crucial role in M98K-OPTN induced autophagosome formation, autophagy flux and retinal cell death. In addition, we provide evidence for cross talk between two glaucoma associated proteins and their inter-dependence to mediate autophagy-dependent cell death. PMID- 26376341 TI - A Real-Time Atrial Fibrillation Detection Algorithm Based on the Instantaneous State of Heart Rate. AB - Atrial fibrillation (AF), the most frequent cause of cardioembolic stroke, is increasing in prevalence as the population ages, and presents with a broad spectrum of symptoms and severity. The early identification of AF is an essential part for preventing the possibility of blood clotting and stroke. In this work, a real-time algorithm is proposed for accurately screening AF episodes in electrocardiograms. This method adopts heart rate sequence, and it involves the application of symbolic dynamics and Shannon entropy. Using novel recursive algorithms, a low-computational complexity can be obtained. Four publicly accessible sets of clinical data (Long-Term AF, MIT-BIH AF, MIT-BIH Arrhythmia, and MIT-BIH Normal Sinus Rhythm Databases) were used for assessment. The first database was selected as a training set; the receiver operating characteristic (ROC) curve was performed, and the best performance was achieved at the threshold of 0.639: the sensitivity (Se), specificity (Sp), positive predictive value (PPV) and overall accuracy (ACC) were 96.14%, 95.73%, 97.03% and 95.97%, respectively. The other three databases were used for independent testing. Using the obtained decision-making threshold (i.e., 0.639), for the second set, the obtained parameters were 97.37%, 98.44%, 97.89% and 97.99%, respectively; for the third database, these parameters were 97.83%, 87.41%, 47.67% and 88.51%, respectively; the Sp was 99.68% for the fourth set. The latest methods were also employed for comparison. Collectively, results presented in this study indicate that the combination of symbolic dynamics and Shannon entropy yields a potent AF detector, and suggest this method could be of practical use in both clinical and out-of clinical settings. PMID- 26376342 TI - Synthesis of Amphiphilic Hyperbranched AIE-active Fluorescent Organic Nanoparticles and Their Application in Biological Application. AB - Aggregation-induced emission (AIE) dyes have recently attracted much attention for biomedical applications for their remarkable AIE properties. However, the hydrophobic nature of AIE dyes made them difficult to be dispersed in physiological solution and problematic for biomedical application directly. Great efforts have been made to overcome this problem, and different strategies for preparation of water dispersible AIE based nanoprobes had been explored previously. However, a facile and effective strategy is still highly desirable and of great importance for the biomedical applications of AIE dye based on nanoprobes. In this work, the fabrication of amphiphilic hyperbranched fluorescent organic nanoparticles with a core-shell structure based on an AIE dye [tetraphenylethene acrylate (TPE-O-E)] and a hyperbranched polyamino compound [polyethylene imine (PEI)] through Michael addition reaction is described for the first time. The AIE dye as well as the final product PEI-TPE-O-E was characterized in detail by a number of techniques. To test their biomedical application potential, the cell viability as well as cell imaging properties of the PEI-TPE-O-E was also examined. The results showed that the PEI-TPE-O-E organic nanoparticles presented high water dispersiblity, ultrabright fluroerescence, low cytotoxicity and excellent biocompatibility, making them promising for biological imaging and gene delivery applications. PMID- 26376343 TI - Exogenous DNA Loading into Extracellular Vesicles via Electroporation is Size Dependent and Enables Limited Gene Delivery. AB - Extracellular vesicles (EVs) hold immense promise for utilization as biotherapeutics and drug delivery vehicles due to their nature as biological nanoparticles that facilitate intercellular molecular transport. Specifically, EVs have been identified as natural carriers of nucleic acids, sparking interest in their use for gene therapy and RNA interference applications. So far, small RNAs (siRNA and miRNA) have been successfully loaded into EVs for a variety of delivery applications, but the potential use of EVs for DNA delivery has scarcely been explored. Here, we report that exogenous linear DNA can be associated with EVs via electroporation in quantities sufficient to yield an average of hundreds of DNA molecules per vesicle. We determined that loading efficiency and capacity of DNA in EVs is dependent on DNA size, with linear DNA molecules less than 1000 bp in length being more efficiently associated with EVs compared to larger linear DNAs and plasmid DNAs using this approach. We further showed that EV size is also determinant with regard to DNA loading, as larger microvesicles encapsulated more linear and plasmid DNA than smaller, exosome-like EVs. Additionally, we confirmed the ability of EVs to transfer foreign DNA loaded via electroporation into recipient cells, although functional gene delivery was not observed. These results establish critical parameters that inform the potential use of EVs for gene therapy and, in agreement with other recent results, suggest that substantial barriers must be overcome to establish EVs as broadly applicable DNA delivery vehicles. PMID- 26376344 TI - Peginterferon Lambda-1a Is Associated with a Low Incidence of Autoimmune Thyroid Disease in Chronic Hepatitis C. AB - Peginterferon alfa (alfa) increases the risk of autoimmune disease. Peginterferon lambda-1a (Lambda) acts through a receptor with a more liver-specific distribution compared to the alfa receptor. In a phase-2b study, 525 treatment naive patients with chronic hepatitis C virus (HCV) infection received ribavirin and Lambda interferon (120, 180, or 240 MUg) or alfa interferon (180 MUg) for 24 (genotypes 2 and 3) or 48 (genotypes 1 and 4) weeks. Retrospective analysis found that adverse events of MedDRA-coded thyroid dysfunction and abnormal levels of thyroid-stimulating hormone (TSH) were significantly more frequent with alfa versus Lambda (12% versus 2.6% and 15.2% versus 3.4%, respectively, both P<0.0001). Most Lambda recipients with abnormal TSH had levels below the lower limit of normal; the frequency of low and high TSH was similar in alfa recipients with abnormal TSH. Blinded review by an endocrinologist found that new-onset primary hypothyroidism or painless thyroiditis was less frequent with Lambda versus alfa (0.5% and 1.8% versus 5.3% and 7.5%, respectively, P<0.0001). Most TSH elevations reflected new-onset hypothyroidism requiring treatment, while most markedly suppressed TSH values reflected probable painless thyroiditis and resolved without sequelae. In conclusion, HCV-infected patients treated with Lambda/ribavirin experienced fewer adverse events of thyroid dysfunction compared with patients treated with alfa/ribavirin. PMID- 26376345 TI - Circadian rhythm in Alzheimer disease after trazodone use. AB - A circadian rhythm is a cycle of approximately 24 h, responsible for many physiological adjustments, and ageing of the circadian clock contributes to cognitive decline. Rhythmicity is severely impaired in Alzheimer disease (AD) and few therapeutic attempts succeeded in improving sleep disorders in such context. This study evaluated sleep parameters by actigraphy in 30 AD patients before and after trazodone use for 2 weeks, and we show a significant improvement in relative rhythm amplitude (RRA), compatible with a more stable daytime behavioral pattern. So, trazodone appears to produce a stabilization of the circadian rhythms in individuals with AD. PMID- 26376346 TI - Effects of Tempol on Experimental Acute Necrotizing Pancreatitis Model in Rats. AB - AIM: We aimed to investigate the effects of Tempol on local organ damage in an experimental acute pancreatitis model. METHODS: This experimental study was conducted on 40 male Wistar- albino rats. The animals were randomly allocated into four groups: (i) Sham-operated group, laparotomies and cannulations of the pancreatic duct without acute necrotizing pancreatitis (ANP) (n=10); (ii) Sham + Tempol group, identical to group 1 except for intravenous tempol treatment for 4 hours (n = 10); (iii) ANP group, glycodeoxycholic acid was infused into the pancreatic duct and cerulein was infused intravenously for 6 hours for development of ANP (n=10); and (iv) ANP + Tempol treated group, in addition to the procedure in group 3, rats were administered tempol intravenously for 4 hours (n = 10). Injury of the pancreas was evaluated histopathologically. Malondialdehyde and myeloperoxidase levels of the pancreatic tissue, blood gas analysis, leukocyte and hematocrit levels were measured. Wet/dry weight of pancreatic tissue was also measured. RESULTS: Serum amylase levels, pancreatic tissue malondialdehyde and myeloperoxidase levels, wet/dry weight ratio, pancreatic edema, acinar necrosis, fat necrosis and hemorrhage, inflammation and perivascular infiltration were significantly lower in the ANP + Tempol group compared with the ANP group. CONCLUSION: Tempol infusion reduced local organ damage due to acute necrotizing pancreatitis in this experimental study. These findings demonstrate that tempol has protective effects on local organ damage due to acute necrotizing pancreatitis in rats. PMID- 26376347 TI - microRNA-26a modulates inflammatory response induced by toll-like receptor 4 stimulation in microglia. AB - MiRNAs, a family of small non-coding RNAs, have emerged as novel post transcriptional regulators of numerous cellular responses. Although the involvement of miRNAs in the regulation of neuroinflammation in various neurological diseases has been previously studied, their role in the production of inflammatory mediators during microglia activation is poorly understood. In this study, the role of miR-26a has been investigated in the modulation of inflammatory response in cultured microglia. Using real-time PCR, the expression of miR-26a was studied in toll-like receptors 4 stimulated primary mouse microglia. miR-26a expression was found to be rapidly reduced after the stimulation of toll-like receptors 4 in microglia. Over-expression of miR-26a significantly decreased the production of inflammatory cytokines such as tumor necrosis factor alpha and IL-6, whereas knockdown of miR-26a increased the expression of these mediators. Furthermore, using in silico analysis, we identified that the activating transcription factor (ATF) 2 is directly targeted by miR-26a. This finding was confirmed by loss and gain of function studies. Similar to the effect of miR-26a over-expression, knockdown of activating transcription factor 2 inhibited the production of proinflammatory cytokines, particularly IL-6. Taken together, our results suggest the involvement of miR-26a in the regulation of the production of proinflammatory cytokines in microglia. We proposed that in microglia, activation of toll-like receptor 4 (TLR4) by lipopolysaccharide (LPS) down-regulates miR-26a. The down-regulation of this miR increases expression of activating transcription factor 2 (ATF2). This event, in addition to the activation of ATF2 by c-Jun N-terminal kinase (JNK), increases interleukin-6 (IL-6) production. On the other hand, miR-26a also increases the production of tumor necrosis factor alpha (TNFalpha) by a mechanism independent of ATF2. PMID- 26376348 TI - Physiological Mechanisms of Weight Gain-Induced Steatosis in People With Obesity. AB - Weight gain is associated with an increase in intrahepatic triglycerides (IHTGs), and is the primary cause of nonalcoholic fatty liver disease in obese individuals. We combined imaging and stable isotope tracer techniques to evaluate the physiologic mechanisms of weight gain-induced steatosis in 27 obese people. Weight gain appeared to increase IHTG content by generating an imbalance between hepatic fatty acid availability and disposal, and resulted in increased hepatic de novo lipogenesis, decreased intrahepatic fatty acid oxidation, and inadequate increases in IHTG export via very low-density lipoprotein secretion. ClinicalTrials.gov ID NCT01184170. PMID- 26376349 TI - Recent Advances From Basic and Clinical Studies of Esophageal Squamous Cell Carcinoma. AB - Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive squamous cell carcinomas and is highly prevalent in Asia. Alcohol and its metabolite, acetaldehyde, are considered definite carcinogens for the esophagus. Polymorphisms in the aldehyde dehydrogenase 2 gene, which encodes an enzyme that eliminates acetaldehyde, have been associated with esophageal carcinogenesis. Studies of the mutagenic and carcinogenic effects of acetaldehyde support this observation. Several recent large-scale comprehensive analyses of the genomic alterations in ESCC have shown a high frequency of mutations in genes such as TP53 and others that regulate the cell cycle or cell differentiation. Moreover, whole genome and whole exome sequencing studies have frequently detected somatic mutations, such as G:C->A:T transitions or G:C->C:G transversions, in ESCC tissues. Genomic instability, caused by abnormalities in the Fanconi anemia DNA repair pathway, is also considered a pathogenic mechanism of ESCC. Advances in diagnostic techniques such as magnifying endoscopy with narrow band imaging or positron emission tomography have increased the accuracy of diagnosis of ESCC. Updated guidelines from the National Comprehensive Cancer Network standardize the practice for the diagnosis and treatment of esophageal cancer. Patients with ESCC are treated endoscopically or with surgery, chemotherapy, or radiotherapy, based on tumor stage. Minimally invasive treatments help improve the quality of life of patients who undergo such treatments. We review recent developments in the diagnosis and treatment of ESCC and advances gained from basic and clinical research. PMID- 26376350 TI - Correlation Between Concentrations of Fecal Calprotectin and Outcomes of Patients With Ulcerative Colitis in a Phase 2 Trial. AB - BACKGROUND & AIMS: Accurate biomarkers of disease activity and therapeutic response can be valuable for clinical trials. We performed a post hoc analysis of data from a phase 2 trial to assess the relationship between the concentration of fecal calprotectin (FCP) and clinical and endoscopic outcomes of patients with moderate to severe ulcerative colitis receiving tofacitinib. METHODS: In a double blind, placebo-controlled, phase 2 trial, 194 patients were assigned randomly to groups given tofacitinib (0.5, 3, 10, or 15 mg twice daily) or placebo. Clinical and endoscopic outcomes were assessed at week 8 using the Mayo scoring system. Receiver operating characteristics were used to evaluate the relationships between FCP concentration and clinical and endoscopic outcomes, and to determine the FCP cut-off concentration that correlated with patient outcome. RESULTS: Week 8 median concentrations of FCP were significantly lower in responders than in nonresponders (P < .001): clinical response, 156 vs 725 mg/kg; clinical remission, 64 vs 617 mg/kg; endoscopic remission, 44 vs 489 mg/kg; and mucosal healing, 127 vs 753 mg/kg. Area-under-the-curve values for FCP receiver operating characteristic models were 0.80 for clinical remission, 0.81 for endoscopic remission, and 0.78 for mucosal healing. An FCP cut-off value of 150 mg/kg achieved the highest summation of sensitivity and specificity for clinical remission (0.68 and 0.79, respectively; kappa coefficient, 0.44) and endoscopic remission (0.79 and 0.75, respectively; kappa coefficient, 0.38). CONCLUSIONS: Concentrations of FCP correlate with clinical and endoscopic outcomes of patients with moderate to severe ulcerative colitis receiving tofacitinib, although at an individual level the agreement was moderate. FCP concentration with a cut-off value of 150 mg/kg had only fair to good accuracy in classifying clinical and endoscopic outcomes in a clinical trial. ClinicalTrials.gov no: NCT00787202. PMID- 26376351 TI - Rapid Protocol Enrollment in Osteosarcoma: A Report From the Children's Oncology Group. PMID- 26376352 TI - Changes in the Supply of US Rural Health Centers, 2000-2011: Implications for Rural Minority Communities. AB - PURPOSE: Rural Health Clinics (RHCs) and Federally Qualified Health Centers (FQHCs) provide primary care in rural areas with a shortage of providers. This paper examines whether racial and ethnic minority composition was related to changes in the supply of RHCs and FQHCs in rural counties from 2000 to 2011. METHODS: We conducted a retrospective cohort study of rural counties using the Area Health Resource File 2012-2013. We examined rural counties defined as non Core-Based Statistical Areas, with complete data on county characteristics for the study period (N = 1,349). Logistic regression analyses estimated associations between percentage of minority residents, and net gains and losses of RHCs and FQHCs, adjusting for total population, percentage of elderly residents, infant mortality rate, poverty rate, and physician, hospital, and clinic supply. Model estimates were used to calculate the predicted probability of outcomes across a range of minority percentage, from the 10th (<=1.6%) to 90th (>=46%) percentile of rural counties. FINDINGS: In high-minority counties, the predicted probability of a net gain in any type of clinic was 28.6% (95% CI: 21.3-35.8), versus 46.4% (95% CI: 40.0-52.8) for low-minority counties. High-minority counties were also more likely to experience a net decline in RHCs. CONCLUSIONS: During a period of substantial growth in both programs, the percentage of minority residents was negatively associated with gaining new clinics of either type. Policy makers may need to consider targeting rural minority communities for additional primary care workforce support. PMID- 26376354 TI - Statistical method for determining and comparing limits of detection of bioassays. AB - The current bioassay development literature lacks the use of statistically robust methods for calculating the limit of detection of a given assay. Instead, researchers often employ simple methods that provide a rough estimate of the limit of detection, often without a measure of the confidence in the estimate. This scarcity of robust methods is likely due to a realistic preference for simple and accessible methods and to a lack of such methods that have reduced the concepts of limit of detection theory to practice for the specific application of bioassays. Here, we have developed a method for determining limits of detection for bioassays that is statistically robust and reduced to practice in a clear and accessible manner geared at researchers, not statisticians. This method utilizes a four-parameter logistic curve fit to translate signal intensity to analyte concentration, which is a curve that is commonly employed in quantitative bioassays. This method generates a 95% confidence interval of the limit of detection estimate to provide a measure of uncertainty and a means by which to compare the analytical sensitivities of different assays statistically. We have demonstrated this method using real data from the development of a paper-based influenza assay in our laboratory to illustrate the steps and features of the method. Using this method, assay developers can calculate statistically valid limits of detection and compare these values for different assays to determine when a change to the assay design results in a statistically significant improvement in analytical sensitivity. PMID- 26376355 TI - Investigation on the ZBG-functionality of phenyl-4-yl-acrylohydroxamic acid derivatives as histone deacetylase inhibitors. AB - A series of alternative Zn-binding groups were explored in the design of phenyl-4 yl-acrylohydroxamic acid derivatives as histone deacetylase (HDAC) inhibitors. Most of the synthesized compounds were less effective than the parent hydroxamic acid. However, the profile of activity shown by the analog bearing a hydroxyurea head group, makes this derivative promising for further investigation. PMID- 26376356 TI - Why and how have drug discovery strategies in pharma changed? What are the new mindsets? AB - In the pharmaceutical industry the long-term challenge of drug innovation is the key phrase throughout R&D that refers to increasing the output of original drug candidate molecules. To increase R&D productivity, implementation of new and strategic R&D orientations to develop new approaches or systems to identify hits and leads efficiently has taken place and enabled all scientists working in the drug discovery domain to develop innovative medicines for the 21st century. PMID- 26376357 TI - Research highlights: elucidation of biogeochemical factors influencing methylmercury production. AB - Coal combustion and other human activities release inorganic mercury into the atmosphere at levels far greater than emissions from natural sources, significantly perturbing the global mercury cycle. Subsequent biogeochemical transformation of inorganic mercury to highly toxic methylmercury allows this heavy metal pollutant to enter the food web, where it bioaccumulates and can have severe impacts on animal and human populations. This Highlight features recent articles that examine in detail the effects of nutrient availability on the methylation-demethylation activity of microorganisms living in sediment with mercury contamination. By investigating differences in levels of sulfate, iron, organic matter, and other environmental factors, this research provides insight into the conditions that may favor methylmercury formation and thereby better inform remediation efforts in the future. PMID- 26376358 TI - Talking About Antismoking Campaigns: What Do Smokers Talk About, and How Does Talk Influence Campaign Effectiveness? AB - Campaign-stimulated conversations have been shown to increase the effectiveness of antismoking campaigns. In order to explore why such effects occur, in the current study we coded the content of naturally occurring conversations. We also examined whether the short-term effects of talking, and of different types of talk, on quitting intentions were mediated through intrapersonal message responses. Using the Natural Exposure(SM) methodology, we exposed 411 smokers to 1 of 6 antismoking advertisements while they were watching television at home. Responses to the advertisement-conversation participation and content, emotional responses, personalized perceived effectiveness, and changes in intentions to quit-were measured within 3 days of exposure. Conversations were coded for appraisal of the advertisement (favorable, neutral, or unfavorable) and the presence of quitting talk and emotion talk. Mediation analyses indicated that the positive effects of talking on intention change were mediated through personalized perceived effectiveness and that the positive effects were driven by conversations that contained a favorable appraisal and/or quitting talk. Conversely, conversations that contained an unfavorable appraisal of the advertisement were negatively associated with campaign effectiveness. These findings highlight the importance of measuring interpersonal communication when evaluating campaigns and the need for further research to identify the message characteristics that predict when smokers talk and when they talk only in desirable ways. PMID- 26376360 TI - Preparation and characterization of a powder containing an oily liquid drug with Eudragit EPO or L100 copolymer. AB - Oily liquid drugs are not convenient for oral administration. We developed a powder containing clofibrate (CF), a model of an oily drug, using aminoalkyl methacrylate copolymer (EPO) or methacrylic acid copolymer (L100). CF or a mixture of CF and soybean oil was emulsified with EPO or L100 aqueous solution. Using a high-pressure homogenizer, a stable emulsion was obtained, and a powder was then obtained by lyophilization of the emulsion. The content of CF in the powder depended on the formulation, with the highest contents being 24.6% and 27.1% for EPO and L100, respectively. The incorporation ratio of CF was higher for L100 than for EPO. The powder using EPO was sticky because of leaked CF and the low glass transition temperature of EPO. The powder using L100 was a typical powder obtained by lyophilization. The leakage of CF from the powder was <2%, lower than for EPO powder. The dissolution of CF from powder using EPO was fast, regardless of the pH of the medium, but the powder using L100 showed enteric soluble characteristics, indicating that CF is well incorporated in L100. PMID- 26376359 TI - [Safety of human papillomavirus 6, 11, 16 and 18 (recombinant): systematic review and meta-analysis]. AB - OBJECTIVE: To identify and quantify the adverse effects associated with the recombinant human papillomavirus (types 6, 11, 16 and 18) vaccine in adolescents. DATA SOURCE: Systematic review of randomized clinical trials from PubMed, SciELO and Lilacs databases. Articles investigating the safety of the vaccine in subjects under 18 years and comparing the recombinant human papillomavirus types 6, 11, 16 and 18 vaccine with a control group were included. Meta-analyses were performed for the outcomes of pain, erythema, swelling and fever, using clinical trials with maximum Jadad score. DATA SYNTHESIS: Fourteen studies were included. The most commons adverse effects related to the human papillomavirus vaccine were effects with no severity (pain, erythema, edema, and fever). Five studies were used for the meta-analyses: Pain-Risk Difference (RD)=11% (p<0.001); edema-RD=8% (p<0.001); erythema-RD=5% (p<0.001); fever-RD=2% (p<0.003). CONCLUSIONS: The recombinant human papillomavirus types 6, 11, 16 and 18 vaccine was safe and well tolerated. The main adverse effects related to vaccination were pain, erythema, edema and fever. The low frequency of severe adverse effects encourages the administration of the vaccine in the population at risk. PMID- 26376361 TI - Expansion of the Journal of Gerontological Social Work Review Section. PMID- 26376362 TI - Bone marrow transplantation alters lung antigen-presenting cells to promote TH17 response and the development of pneumonitis and fibrosis following gammaherpesvirus infection. AB - Hematopoietic stem cell transplantation (HSCT) efficacy is limited by numerous pulmonary complications. We developed a model of syngeneic bone marrow transplantion (BMT) followed by infection with murine gamma herpesvirus-68 that results in pneumonitis and fibrosis and mimics human "noninfectious" HSCT complications. BMT mice experience increased early lytic replication, but establish viral latency by 21 days post infection. CD4 T cells in BMT mice are skewed toward interleukin (IL)-17A rather than interferon (IFN)-gamma production. Transplantation of bone marrow from Il-17a(-/-) donors or treatment with anti-IL 17A neutralization antibodies at late stages attenuates pneumonitis and fibrosis in infected BMT mice, suggesting that hematopoietic-derived IL-17A is essential for development of pathology. IL-17A directly influences activation and extracellular matrix production by lung mesenchymal cells. Lung CD11c+ cells of BMT mice secrete more transforming growth factor beta-beta1, and pro-TH17 mRNAs for IL-23 and IL-6, and less TH1-promoting cytokine mRNA for IFN-gamma but slightly more IL-12 mRNA in response to viral infection. Adoptive transfer of non BMT lung CD11c-enriched cells restores robust TH1 response and suppresses aberrant TH17 response in BMT mice to improve lung pathology. Our data suggest that "noninfectious" HSCT lung complications may reflect preceding viral infections and demonstrate that IL-17A neutralization may offer therapeutic advantage even after disease onset. PMID- 26376363 TI - Double-negative T resident memory cells of the lung react to influenza virus infection via CD11c(hi) dendritic cells. AB - Immunity to Influenza A virus (IAV) is controlled by conventional TCRalphabeta(+) CD4(+) and CD8(+) T lymphocytes, which mediate protection or cause immunopathology. Here, we addressed the kinetics, differentiation, and antigen specificity of CD4(-)CD8(-) double-negative (DN) T cells. DNT cells expressed intermediate levels of TCR/CD3 and could be further divided in gammadelta T cells, CD1d-reactive type I NKT cells, NK1.1(+) NKT-like cells, and NK1.1(-) DNT cells. NK1.1(-) DNT cells had a separate antigen-specific repertoire in the steady-state lung, and expanded rapidly in response to IAV infection, irrespectively of the severity of infection. Up to 10% of DNT cells reacted to viral nucleoprotein. Reinfection experiments with heterosubtypic IAV revealed that viral replication was a major trigger for recruitment. Unlike conventional T cells, the NK1.1(-) DNT cells were in a preactivated state, expressing memory markers CD44, CD11a, CD103, and the cytotoxic effector molecule FasL. DNT cells resided in the lung parenchyma, protected from intravascular labeling with CD45 antibody. The recruitment and maintenance of CCR2(+) CCR5(+) CXCR3(+) NK1.1(-) DNT cells depended on CD11c(hi) dendritic cells (DCs). Functionally, DNT cells controlled the lung DC subset balance, suggesting they might act as immunoregulatory cells. In conclusion, we identify activation of resident memory NK1.1(-) DNT cells as an integral component of the mucosal immune response to IAV infection. PMID- 26376364 TI - A CCL24-dependent pathway augments eosinophilic airway inflammation in house dust mite-challenged Cd163(-/-) mice. AB - CD163 is a macrophage scavenger receptor with anti-inflammatory and pro inflammatory functions. Here, we report that alveolar macrophages (AMPhis) from asthmatic subjects had reduced cell-surface expression of CD163, which suggested that CD163 might modulate the pathogenesis of asthma. Consistent with this, house dust mite (HDM)-challenged Cd163(-/-) mice displayed increases in airway eosinophils and mucous cell metaplasia (MCM). The increased airway eosinophils and MCM in HDM-challenged Cd163(-/-) mice were mediated by augmented CCL24 production and could be reversed by administration of a neutralizing anti-CCL24 antibody. A proteomic analysis identified the calcium-dependent binding of CD163 to Dermatophagoides pteronyssinus peptidase 1 (Der p1). Der p1-challenged Cd163( /-) mice had the same phenotype as HDM-challenged Cd163(-/-) mice with increases in airway eosinophils, MCM and CCL24 production, while Der p1 induced CCL24 secretion by bone marrow-derived macrophages (BMMPhis) from Cd163(-/-) mice, but not BMMPhis from wild-type (WT) mice. Finally, airway eosinophils and bronchoalveolar lavage fluid CCL24 levels were increased in Der p1-challenged WT mice that received adoptively transferred AMPhi's from Cd163(-/-) mice. Thus, we have identified CD163 as a macrophage receptor that binds Der p1. Furthermore, we have shown that HDM-challenged Cd163(-/-) mice have increased eosinophilic airway inflammation and MCM that are mediated by a CCL24-dependent mechanism. PMID- 26376365 TI - A secretory leukocyte protease inhibitor variant with improved activity against lung infection. AB - Secretory leukocyte protease inhibitor (SLPI) is an important respiratory tract host defense protein, which is proteolytically inactivated by excessive neutrophil elastase (NE) during chronic Pseudomonas infection in the cystic fibrosis (CF) lung. We generated two putative NE-resistant variants of SLPI by site-directed mutagenesis, SLPI-A16G and SLPI-S15G-A16G, with a view to improving SLPI's proteolytic stability. Both variants showed enhanced resistance to degradation in the presence of excess NE as well as CF patient sputum compared with SLPI-wild type (SLPI-WT). The ability of both variants to bind bacterial lipopolysaccharides and interact with nuclear factor-kappaB DNA binding sites was also preserved. Finally, we demonstrate increased anti-inflammatory activity of the SLPI-A16G protein compared with SLPI-WT in a murine model of pulmonary Pseudomonas infection. This study demonstrates the increased stability of these SLPI variants compared with SLPI-WT and their therapeutic potential as a putative anti-inflammatory treatment for CF lung disease. PMID- 26376366 TI - CD4 T cells are required for both development and maintenance of disease in a new mouse model of reversible colitis. AB - Current therapies to treat inflammatory bowel diseases have limited efficacy, significant side effects, and often wane over time. Little is known about the cellular and molecular mechanisms operative in the process of mucosal healing from colitis. To study such events, we developed a new model of reversible colitis in which adoptive transfer of CD4(+)CD45RB(hi) T cells into Helicobacter typhlonius-colonized lymphopenic mice resulted in a rapid onset of colonic inflammation that was reversible through depletion of colitogenic T cells. Remission was associated with an improved clinical and histopathological score, reduced immune cell infiltration to the intestinal mucosa, altered intestinal gene expression profiles, regeneration of the colonic mucus layer, and the restoration of epithelial barrier integrity. Notably, colitogenic T cells were not only critical for induction of colitis but also for maintenance of disease. Depletion of colitogenic T cells resulted in a rapid drop in tumor necrosis factor alpha (TNFalpha) levels associated with reduced infiltration of inflammatory immune cells to sites of inflammation. Although neutralization of TNFalpha prevented the onset of colitis, anti-TNFalpha treatment of mice with established disease failed to resolve colonic inflammation. Collectively, this new model of reversible colitis provides an important research tool to study the dynamics of mucosal healing in chronic intestinal remitting-relapsing disorders. PMID- 26376367 TI - Assessing DNA methylation in the developing human intestinal epithelium: potential link to inflammatory bowel disease. AB - DNA methylation is one of the major epigenetic mechanisms implicated in regulating cellular development and cell-type-specific gene expression. Here we performed simultaneous genome-wide DNA methylation and gene expression analysis on purified intestinal epithelial cells derived from human fetal gut, healthy pediatric biopsies, and children newly diagnosed with inflammatory bowel disease (IBD). Results were validated using pyrosequencing, real-time PCR, and immunostaining. The functional impact of DNA methylation changes on gene expression was assessed by employing in-vitro assays in intestinal cell lines. DNA methylation analyses allowed identification of 214 genes for which expression is regulated via DNA methylation, i.e. regulatory differentially methylated regions (rDMRs). Pathway and functional analysis of rDMRs suggested a critical role for DNA methylation in regulating gene expression and functional development of the human intestinal epithelium. Moreover, analysis performed on intestinal epithelium of children newly diagnosed with IBD revealed alterations in DNA methylation within genomic loci, which were found to overlap significantly with those undergoing methylation changes during intestinal development. Our study provides novel insights into the physiological role of DNA methylation in regulating functional maturation of the human intestinal epithelium. Moreover, we provide data linking developmentally acquired alterations in the DNA methylation profile to changes seen in pediatric IBD. PMID- 26376369 TI - Exploring the association between working memory and driving performance in Parkinson's disease. AB - OBJECTIVE: The aim of this study was to explore whether varying levels of operational and tactical driving task demand differentially affect drivers with Parkinson's disease (PD) and control drivers in their sign recall. METHODS: Study participants aged between 50 and 70 years included a group of drivers with PD (n = 10) and a group of age- and sex-matched control drivers (n = 10). Their performance in a sign recall task was measured using a driving simulator. RESULTS: Drivers in the control group performed better than drivers with PD in a sign recall task, but this trend was not statistically significant (P =.43). In addition, regardless of group membership, subjects' performance differed according to varying levels of task demand. Performance in the sign recall task was more likely to drop with increasing task demand (P =.03). This difference was significant when the variation in task demand was associated with a cognitive task; that is, when drivers were required to apply the instructions from working memory. CONCLUSIONS: Although the conclusions drawn from this study are tentative, the evidence presented here is encouraging with regard to the use of a driving simulator to examine isolated cognitive functions underlying driving performance in PD. With an understanding of its limitations, such driving simulation in combination with functional assessment batteries measuring physical, visual, and cognitive abilities could comprise one component of a multitiered system to evaluate medical fitness to drive. PMID- 26376368 TI - Gut immune dysfunction through impaired innate pattern recognition receptor expression and gut microbiota dysbiosis in chronic SIV infection. AB - HIV targets the gut mucosa early in infection, causing immune and epithelial barrier dysfunction and disease progression. However, gut mucosal sensing and innate immune signaling through mucosal pattern recognition receptors (PRRs) during HIV infection and disease progression are not well defined. Using the simian immunodeficiency virus (SIV)-infected rhesus macaque model of AIDS, we found a robust increase in PRRs and inflammatory cytokine gene expression during the acute SIV infection in both peripheral blood and gut mucosa, coinciding with viral replication. PRR expression remained elevated in peripheral blood following the transition to chronic SIV infection. In contrast, massive dampening of PRR expression was detected in the gut mucosa, despite the presence of detectable viral loads. Exceptionally, expression of Toll-like receptor 4 (TLR4) and TLR8 was downmodulated and diverged from expression patterns for most other TLRs in the gut. Decreased mucosal PRR expression was associated with increased abundance of several pathogenic bacterial taxa, including Pasteurellaceae members, Aggregatibacter and Actinobacillus, and Mycoplasmataceae family. Early antiretroviral therapy led to viral suppression but only partial maintenance of gut PRRs and cytokine gene expression. In summary, SIV infection dampens mucosal innate immunity through PRR dysregulation and may promote immune activation, gut microbiota changes, and ineffective viral clearance. PMID- 26376370 TI - How Peer Communication and Engagement Motivations Influence Social Media Shopping Behavior: Evidence from China and the United States. AB - Based on consumer socialization theory, this study proposes and tests a conceptual model of social media shopping behavior, which links the antecedents of user motivations of engagement and peer communication about products to shopping behavior through social media. A cross-cultural survey was conducted with social media users in two culturally distinct markets with the largest Internet population: China (n=304) and the United States (n=328). Findings showed that social interaction, information, and remuneration were positive antecedents of peer communication for users from both countries. Peer communication positively impacted social media shopping behavior, and cultural differences were observed, with social interaction being important to Chinese users' shopping behavior, while remuneration was more important to American users. Implications are discussed. PMID- 26376372 TI - High Sodium Intake Is Associated With Self-Reported Rheumatoid Arthritis: A Cross Sectional and Case Control Analysis Within the SUN Cohort. AB - Sodium intake is a potential environmental factor for immune-mediated inflammatory diseases. The aim of this study is to investigate the association of sodium intake with rheumatoid arthritis. We performed a cross-sectional study nested in a highly educated cohort investigating dietary habits as determinants of disease. Daily sodium intake in grams per day was estimated from a validated food frequency questionnaire. We identified prevalent self-reported cases of rheumatoid arthritis. Logistic regression models were used to estimate the odds ratio for rheumatoid arthritis by sodium intake adjusting for confounders. Linear trend tests and interactions between variables were explored. Sensitivity analyses included age- and sex-matched case-control study, logistic multivariate model adjusted by residuals, and analysis excluding individuals with prevalent diabetes or cardiovascular disease. The effective sample size was 18,555 individuals (mean age 38-years old, 60% women) including 392 self-reported rheumatoid arthritis. Median daily sodium intake (estimated from foods plus added salt) was 3.47 (P25-75: 2.63-4.55) grams. Total sodium intake in the fourth quartile showed a significant association with rheumatoid arthritis (fully adjusted odds ratio 1.5; 95% CI 1.1-2.1, P for trend = 0.02). Never smokers with high sodium intake had higher association than ever smokers with high sodium intake (P for interaction = 0.007). Dose-dependent association was replicated in the case-control study. High sodium intake may be associated with a diagnosis of rheumatoid arthritis. This confirms previous clinical and experimental research. PMID- 26376373 TI - Genetic Association Between Angiotensinogen Polymorphisms and Lung Cancer Risk. AB - Earlier published studies investigating the association between polymorphisms in the angiotensinogen gene and lung cancer risk showed no consistent results. In this study, we have summarized all currently available data to examine the correlation by meta-analysis. Case-control studies addressing the association being examined were identified through Embase, the Cochrane Library, ISI Web of Science (Web of Knowledge), Google Scholar, PubMed, and CNKI databases. Risk of lung cancer (odds ratio [OR] and 95% confidence interval [CI]) was estimated with the fixed or the random effects model assuming homozygous, allele, heterozygous, dominant, and recessive models for all angiotensinogen polymorphisms. We identified a total of 10 articles in this meta-analysis, including 7 for Leu84Phe, 4 for Ile143Val, and 3 for Leu53Leu. In the meta-analysis of Leu84Phe polymorphism, the homozygous model provided an OR of 1.44 (Phe/Phe vs Ile/Ile: OR = 1.44, 95% CI = 1.04-1.99, P values for heterogeneity test (Q-test) [P(Het)] = 0.382). The significantly increased risk was similarly indicated in the recessive model (Phe/Phe vs Phe/Ile + Ile/Ile: OR = 1.41, 95% CI = 1.02-1.95, P(Het) = 0.381). We also observed a positive association in the Caucasian subgroup. The heterozygous model and the dominant model tested for the Ile143Val polymorphism showed a marginally increased risk (Ile/Val vs Ile/Ile: OR = 1.16, 95% CI = 1.00 1.36, P(Het) = 0.323; Val/Val + Ile/Val vs Ile/Ile: OR = 1.15, 95% CI = 0.99 1.34, P(Het) = 0.253). These data suggest that Leu84Phe and Ile143Val polymorphisms in the angiotensinogen gene may be useful biomarkers for lung cancer in some specific populations. PMID- 26376374 TI - Association Between SLCO1B1 Gene T521C Polymorphism and Statin-Related Myopathy Risk: A Meta-Analysis of Case-Control Studies. AB - Statin-related myopathy is an important adverse effect of statin which is classically unpredictable. The evidence of association between solute carrier organic anion transporter 1B1 (SLCO1B1) gene T521C polymorphism and statin related myopathy risk remained controversial. This study aimed to investigate this genetic association. Databases of PubMed, EMBASE, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database, and Wanfang Data were searched till June 17, 2015. Case-control studies investigating the association between SLCO1B1 gene T521C polymorphism and statin-related myopathy risk were included. The Newcastle Ottawa Scale (NOS) was used for assessing the quality of included studies. Data were pooled by odds ratios (ORs) and their 95% confidence intervals (CIs). Nine studies with 1360 cases and 3082 controls were included. Cases of statin-related myopathy were found to be significantly associated with the variant C allele (TC + CC vs TT: OR = 2.09, 95% CI = 1.27-3.43, P = 0.003; C vs T: OR = 2.10, 95% CI = 1.43-3.09, P < 0.001), especially when statin-related myopathy was defined as an elevation of creatine kinase (CK) >10 times the upper limit of normal (ULN) or rhabdomyolysis (TC + CC vs TT: OR = 3.83, 95% CI = 1.41-10.39, P = 0.008; C vs T: OR = 2.94, 95% CI = 1.47-5.89, P = 0.002). When stratified by statin type, the association was significant in individuals receiving simvastatin (TC + CC vs TT: OR = 3.09, 95% CI = 1.64-5.85, P = 0.001; C vs T: OR = 3.00, 95% CI = 1.38-6.49, P = 0.005), but not in those receiving atorvastatin (TC + CC vs TT: OR = 1.31, 95% CI = 0.74-2.30, P = 0.35; C vs T: OR = 1.33, 95% CI = 0.57-3.12, P = 0.52). The available evidence suggests that SLCO1B1 gene T521C polymorphism is associated with an increased risk of statin-related myopathy, especially in individuals receiving simvastatin. Thus, a genetic test before initiation of statins may be meaningful for personalizing the treatment. PMID- 26376375 TI - Diagnostic Value of MicroRNAs for Urologic Cancers: A Systematic Review and Meta Analysis. AB - MicroRNAs (miRNAs), particularly those extracted from the blood or tissues, have become the focus of urologic cancers research. However, the literature reviews on the accuracy of miRNA detection in urologic cancers have been inconsistent, leading us to perform this meta-analysis. Eligible studies were searched in PubMed and other databases. To calculate the pooled detection accuracy estimates, we used a bivariate random-effects meta-analysis model. According to the exclusion and inclusion criteria, 41 studies were included. Overall, the results showed sensitivity of 0.77 (95% CI: 0.74-0.80) and specificity of 0.76 (95% CI: 0.72-0.79), with an area under the SROC curve (AUC) of 0.83 (95% CI: 0.80-0.86). In addition, further subgroup analyses were also conducted. Firstly, the multiple miRNAs subgroup has significantly better diagnostic specificity than single miRNA subgroup among all these cancer types, while only bladder cancer (BC) and prostate cancer (PC) group with significantly greater diagnostic sensitivity with their multiple miRNA detection. Secondly, none of these cancer types showed significant differences on diagnostic sensitivity and specificity in their specimen and sample size subgroups. Thirdly, the diagnostic sensitivity between Asian (0.791, 95% CI: 0.748-0.827) and Caucasian (0.713, 95% CI: 0.666-0.756) in BC type was shown significant different with the P-value of 0.011. The results of our study suggested that miRNAs, particularly the multiple miRNAs, may play an important role in diagnosis and monitoring of the urologic cancers as superior biomarkers. PMID- 26376377 TI - Clinical Diagnostic Implications of Body Fluid MiRNA in Oral Squamous Cell Carcinoma: A Meta-Analysis. AB - Oral cancer, predominantly oral squamous cell carcinoma (OSCC), is one of the most leading causes of cancers worldwide. Due to a low 5-year survival rate, highly effective methods for the early detection of OSCC are totally needed. MicroRNAs (miRNAs), as promising biomarkers, can bring insights into tumorigenesis of oral cancers. However, studies on the accuracy of miRNAs detection in OSCC have inconsistent conclusions, leading us to conduct this meta analysis. The aim of this study was to systematically review the articles investigating the diagnostic value of miRNAs in OSCC. The PubMed, Embase, Chinese National Knowledge Infrastructure (CNKI), Web of Science were searched (updated to June 11th, 2015) to identify all articles evaluating the diagnostic yield of miRNAs for OSCC. The pooled sensitivity, specificity, and other diagnostic parameters were used to assess the performance of miRNAs assays on OSCC detection. Statistical analysis was conducted by employing the R software. The present meta-analysis comprised 23 studies from 10 articles, including 598 OSCC patients and 320 healthy individuals, available for analysis. The summary receiver operator characteristic (SROC) curve was plotted. Meanwhile, the pooled diagnostic parameters and the area under curve (AUC) were calculated based on all included studies. The pooled diagnostic parameters calculated from all 23 studies were as follows: pooled sensitivity of 0.759 (95% CI: 0.701-0.809), pooled specificity of 0.773 (95% CI: 0.713-0.823) and AUC of 0.832, which indicates a relatively high diagnostic accuracy of miRNAs in differentiating OSCC patients from healthy controls. Meanwhile, In addition, subgroup analyses were conducted to access the heterogeneity between studies, which is based on specimen (serum/plasma/blood/saliva/ tissue) and ethnicity (Asian/Caucasian). In summary, our meta-analysis suggests that miRNAs might be used in noninvasive screening tests for OSCC, which needs further large-scale studies to be validated. PMID- 26376376 TI - Association of Extrarenal Adverse Effects of Posttransplant Immunosuppression With Sex and ABCB1 Haplotypes. AB - Extrarenal adverse effects (AEs) associated with calcineurin inhibitor (CNI) and mycophenolic acid (MPA) occur frequently but are unpredictable posttransplant complications. AEs may result from intracellular CNI accumulation and low activity of P-glycoprotein, encoded by the ABCB1 gene. Since ABCB1 single nucleotide polymorphisms (SNPs) and sex influence P-glycoprotein, we investigated haplotypes and extrarenal AEs. A prospective, cross-sectional study evaluated 149 patients receiving tacrolimus and enteric coated mycophenolate sodium or cyclosporine and mycophenolate mofetil. Immunosuppressive AE assessment determined individual and composite gastrointestinal, neurologic, aesthetic, and cumulative AEs. Lipids were quantitated after 12-hour fast. ABCB1 SNPs: c.1236C>T (rs1128503), c.2677G>T/A (rs2032582), and c.3435C>T (rs1045642) were determined with haplotype associations computed using the THESIAS program, and evaluated by immunosuppression, sex and race using multivariate general linear models. Tacrolimus patients exhibited more frequent and higher gastrointestinal AE scores compared with cyclosporine with association to CTT (P = 0.018) and sex (P = 0.01). Aesthetic AE score was 3 times greater for cyclosporine with TTC haplotype (P = 0.005). Females had higher gastrointestinal (P = 0.022), aesthetic (P < 0.001), neurologic (P = 0.022), and cumulative AE ratios (P < 0.001). Total cholesterol (TCHOL), low-density lipoproteins (LDL), and triglycerides were higher with cyclosporine. The TTC haplotype had higher TCHOL (P < 0.001) and LDL (P = 0.005). Higher triglyceride (P = 0.034) and lower high-density lipoproteins (P = 0.057) were associated with TTT with sex-adjusted analysis. ABCB1 haplotypes and sex were associated with extrarenal AEs. Using haplotypes, certain female patients manifested more AEs regardless of CNI. Haplotype testing may identify patients with greater susceptibility to AEs and facilitate CNI individualization. PMID- 26376378 TI - Risk of Ischemic Stroke in Patients With Gastric Cancer: A Nationwide Population Based Cohort Study. AB - Improvements in therapeutic modalities have prolonged the survival of gastric cancer patients. Comorbidities such as thromboembolic events that emerge as a result of disease complexities and/or treatments received have not been considered. The objectives of this study are to examine the relationship between gastric cancer and ischemic stroke, and to determine predictive risk factors. A nationwide population-based cohort study was conducted using data from the Taiwan National Health Insurance database. A total of 45,060 gastric cancer patients and non-cancer counterparts without antecedent stroke were recruited. Hazard ratios (HRs) and the cumulative incidence of ischemic stroke were calculated, and risk factors for ischemic stroke were assessed. Gastric cancer patients were associated with higher risk of ischemic stroke (HR 1.11, 95% confidence interval [CI] 1.03-1.19, P = 0.007), especially in participants younger than 65 years (HR 1.61, 95% CI 1.39-1.86, P < 0.001) and in female participants (HR 1.30, 95% CI 1.14-1.49; P < 0.001) when compared with the matched cohort. Independent risk factors of ischemic stroke in gastric cancer patients included age, hypertension, atrial fibrillation, dyslipidemia, and having received major surgery for gastric cancer. Our findings suggest the importance of stroke surveillance and prevention strategies in high-risk patients. Having received major surgery for gastric cancer is a significant risk factor in these patients. PMID- 26376379 TI - Prevalence, Patterns, and Clinical Predictors of Left Ventricular Late Gadolinium Enhancement in Patients Undergoing Cardiac Magnetic Resonance Prior to Pulmonary Vein Antral Isolation for Atrial Fibrillation: A Cross-Sectional Observational Study. AB - Cardiac magnetic resonance (CMR) imaging is increasingly used to evaluate patients with atrial fibrillation (AF) before pulmonary vein antral isolation (PVAI). The purpose of this study was to assess the incidence and pattern of left ventricular (LV) late gadolinium enhancement (LGE) in patients undergoing CMR before PVAI and compare the clinical and demographic differences of patients with and without LV LGE. Clinical and demographic data on 62 patients (mean age 61 +/- 7.9, 69% male) undergoing CMR before PVAI for AF were collected. Two observers, masked to clinical histories, independently recorded the prevalence, extent (number of myocardial segments), and pattern (subendocardial, midmyocardial, or subepicardial) of LV LGE in each patient. Clinical and demographic predictors of LV LGE were determined using logistic regression. Twenty-three patients (37%) demonstrated LV LGE affecting a mean of 3.0 +/- 2.1 myocardial segments. There was no difference in LV ejection fraction between patients with and without LGE, and most (65%) patients with LGE had normal wall motion. Only age (P = 0.04) and a history of congestive heart failure (P = .03) were statistically significant independent predictors of LGE. The most common LGE pattern was midmyocardial, seen in 17 of 23 (74%) patients. Only 4 of 23 (17%) patients had LGE in an "expected" pattern based on clinical history. Of the remaining 19 patients, 4 had known congestive heart failure, 5 nonischemic cardiomyopathy, 4 known coronary artery disease, and 2 prior aortic valve replacement. Six of 23 (26%) patients had no known coronary artery, valvular, or myocardial disease. There is a high prevalence of unexpected LV scar in patients undergoing CMR before PVAI for AF, with most patients demonstrating a nonischemic pattern of LV LGE and no wall motion abnormalities (ie, subclinical disease). The high prevalence of unexpected LGE in these patients may argue for CMR as the modality of choice for imaging integration before PVAI, especially given the demonstrated prognostic value of LGE in this and other patient populations. PMID- 26376380 TI - Folic Acid Intake and Neural Tube Defects: Two Egyptian Centers Experience. AB - Neural tube defects (NTDs) are a group of congenital malformations with worldwide distribution and complex etiopathogenesis. Folic acid plays a pivotal role in their prevention. We aimed to identify the protective effect of folic acid intake against NTDs and its dependence on different socioeconomic and environmental factors in a cohort of mothers in Egypt. A cross-sectional study was carried over a period of 12 months on mothers who gave birth to babies with NTDs (group 1) and a control group with healthy offsprings (group 2). Both groups completed 2 questionnaires: food frequency questionnaire targeting the daily folate intake, and socioeconomic status and medical history questionnaire. Both groups of mothers received folate <800 MUg/day, recommended for pregnant women. A strong association was detected between NTDs and urban residency with medium educated mothers, with negative consanguinity, who had folate intake < 400 MUg daily, and who had their food long cooked. Each of these factors separately had a limited impact to cause NTDs, but when present together they did augment each other. Interestingly enough is the role of fava bean, cauliflower, spinach, and mango in predisposing of NTDs in the presence of the above-mentioned factors. The protective effect of folic acid intake against NTDs may depend on the synergism of different socioeconomic and environmental factors (which differ from country to another). In Egypt, females especially the medium-educated who live in urban areas should be well-informed with the value of folate intake in the periconceptional period. PMID- 26376381 TI - Default Mode Connectivity in Youth With Perinatally Acquired HIV. AB - Youth with perinatally acquired human immunodeficiency virus (PHIV+) survive longer with combination antiretroviral therapy, but remain at risk for poor cognitive outcomes. We evaluated whether markers of HIV disease severity relate to default mode resting-state functional connectivity in PHIV+ youth. We conducted resting-state functional neuroimaging and cognitive testing in a subset of 40 PHIV+ youth recruited from a single study site of the Adolescent Master Protocol study conducted by the Pediatric HIV/AIDS Cohort Study (PHACS) network. Current and past HIV disease severity measures (nadir CD4 lymphocyte percentages and peak HIV RNA plasma levels) were obtained from medical charts. We evaluated associations of both HIV disease severity measures and cognitive functioning with between- and within- default mode network (DMN) connectivity using Analysis of Functional NeuroImaging multiple regression analyses, controlling for multiple comparisons. Of the 40 youth, 31 (mean age = 16.5 years) with minimal motion during scans were included. We observed global alterations in DMN within- and between-network connectivity, with significant associations between disease severity and DMN BOLD correlations. Furthermore, patterns of connectivity with the posterior cingulate cortex (PCC) and medial prefrontal cortex (mPFC) that varied as a function of peak HIV RNA were found to predict processing speed ability. Alterations in within- and between-network DMN connectivity in PHIV+ youth may reflect global reorganization of the DMN; this could lead to compensatory alterations in both the within- and between-connectivity of large scale networks, which may ultimately relate to known cognitive processing difficulties in PHIV+ youth. PMID- 26376382 TI - The Prognostic Value of Platelet Count in Patients With Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis. AB - Thrombocytopenia has been acknowledged to be a crucial risk factor for cirrhosis formation and hepatocarcinogenesis in chronic liver diseases. However, to date, the association between platelet count (PLT) and the prognosis of hepatocellular carcinoma (HCC) remains inconsistent and controversial. The aim of the present study was to determine whether PLT could be used as a useful predictor of survival in patients with HCC. We performed systematic review in online databases, including PubMed, EmBase, and Web of Science, from inception until 2014. Studies were included if a statistical relationship was investigated between PLT and survival for HCC, and hazard ratio (HR) and 95% confidence intervals (CIs) for overall survival (OS) or recurrence-free survival (RFS) were provided. The quality of each included study was assessed by Newcastle-Ottawa scale score. To synthesize these studies, a random-effects model or a fixed effects model was applied as appropriate. Then, we calculated heterogeneity, performed sensitivity analysis, tested publication bias, and did subgrouped and meta-regression analysis. Finally, we identified 33 eligible articles (published from 1998 to 2014) involved 5545 patients by retrieval. A low level of preoperative PLT was found to be significantly associated with a poor survival of HCC. Irrespective of the therapy used, the pooled HRs for OS and RFS were 1.41 (95% CI, 1.14-1.75) and 1.44 (95% CI, 1.13-1.83), respectively. Specifically, in patients who underwent liver resection, the pooled HRs for OS and RFS were 1.67 (95% CI, 1.22-2.27) and 1.44 (95% CI, 1.04-1.99), respectively. Furthermore, patients with preoperative thrombocytopenia (PLT < 100 * 109/L) had a worse OS (HR: 1.73, 95% CI, 1.29-2.32) and RFS (HR: 1.57, 95% CI, 1.31-1.87) in comparison with patients without thrombocytopenia. All our findings showed no significant changes due to the removal of any study or the use of an opposite-effects model, and there was no significant publication bias. The limitations of this meat analysis were nonuniform cut-off values of PLT, high between-study heterogeneities, potential confounders, and a bias of publication year. A low preoperative PLT level results in an unfavorable outcome in HCC. PLT is a simple, inexpensive, and useful predictor of survival in patients with HCC. PMID- 26376383 TI - Measuring the Potential Impact of Combination HIV Prevention in Sub-Saharan Africa. AB - A public health approach to combination HIV prevention is advocated to contain the epidemic in sub-Saharan Africa. We explore the implications of universal access to treatment along with HIV education scale-up in the region. We develop an HIV transmission model to investigate the impacts of universal access to treatment, as well as an analytical framework to estimate the effects of HIV education scale-up on the epidemic. We calibrate the model with data from South Africa and simulate the impacts of universal access to treatment along with HIV education scale-up on prevalence, incidence, and HIV-related deaths over a course of 15 years. Our results show that the impact of combined interventions is significantly larger than the summation of individual intervention impacts (super additive property). The combined strategy of universal access to treatment and HIV education scale-up decreases the incidence rate by 74% over the course of 15 years, whereas universal access to treatment and HIV education scale up will separately decrease that by 43% and 8%, respectively. Combination HIV prevention could be notably effective in transforming HIV epidemic to a low-level endemicity. Our results suggest that in designing effective combination prevention in sub-Saharan Africa, priorities should be given to achieving universal access to treatment as quickly as possible and improving compliance to condom use. PMID- 26376384 TI - Renal Presentation in Pediatric Acute Leukemia: Report of 2 Cases. AB - Renal enlargement at time of diagnosis of acute leukemia is very unusual. We here in report 2 pediatric cases of acute leukemia who had their renal affection as the first presenting symptom with no evidences of blast cells in blood smear and none of classical presentation of acute leukemia. The first case is a 4-year-old girl who presented with pallor and abdominal enlargement. Magnetic resonance imaging showed bilateral symmetrical homogenous enlarged kidneys suggestive of infiltration. Complete blood picture (CBC) revealed white blood count 11 * 109/L, hemoglobin 8.7 g/dL and platelet count 197 * 109/L. Bone marrow aspiration was performed, and diagnosed precursor B-cell ALL was made. The child had an excellent response to modified CCG 1991 standard risk protocol of chemotherapy with sustained remission, but unfortunately relapsed 11 month after the end of therapy. The second child was 13-month old, presented with pallor, vomiting, abdominal enlargement, and oliguria 2 days before admission. Initial CBC showed bicytopenia, elevated blood urea, creatinine, and serum uric acid, while abdominal ultrasonography revealed bilateral renal enlargement. Bone marrow examination was done and showed 92% blast of biphenotypic nature. So, biphynotypic leukemia with bilateral renal enlargement and acute renal failure was subsequently diagnosed. The patients admitted to ICU and received supportive care and prednisolone. Renal function normalized and chemotherapy was started. The child achieved complete remission with marked reduction of kidney size but, unfortunately she died from sepsis in consolidation phase of therapy. This case demonstrates an unusual early renal enlargement in childhood acute leukemia. Renal involvement of acute leukemia should be considered in child presenting with unexplained bilateral renal enlargement with or without renal function abnormalities and bone marrow examination should be included in the workup. PMID- 26376385 TI - Functional Outcome Changes in Surgery for Pituitary Adenomas After Intraoperative Occurrence of the Trigeminocardiac Reflex: First Description in a Retrospective Observational Study. AB - Trigeminocardiac reflex (TCR) represents now a nearly ubiquitary phenomenon in skull base surgery. Functional relevance of the intrainterventional TCR occurrence is hitherto only proven for vestibular schwannoma. In a retrospective observational study, 19 out of 338 (8%) enrolled adult patients demonstrated a TCR during transsphenoidal/transcranial surgery for pituitary adenomas. The 2 subgroups (TCR vs non-TCR) had similar patient's characteristics, risk factors, and histology. Preoperatively, there was a similar distribution of normal pituitary function in the TCR and non-TCR subgroups. In this TCR subgroup, there was a significant decrease of that normal pituitary function after operation (37%) compared to the non-TCR group (60%) (P < 0.03). The TCR subgroup therefore demonstrated a 3.15 times (95%CI 1.15-8.68) higher risk for non-normalizing of postoperative pituitary function compared with the non-TCR subgroup (P < 0.03). It is presented, for the first time, an impact of TCR on the functional hormonal outcome after pituitary surgery and strongly underline again the importance of the TCR in clinical daily practice. As a consequence, TCR should be considered as a negative prognostic factor of hormonal normalization after surgery for pituitary adenomas that should be included into routine practice. PMID- 26376386 TI - Preexisting Diabetes and Risks of Morbidity and Mortality After Gastrectomy for Gastric Cancer: A Nationwide Database Study. AB - The purpose of this study was to determine the risk of surgical mortality and morbidity in patients with diabetes mellitus (DM) undergoing a gastrectomy for gastric cancer (GC). Using the Taiwan National Health Insurance Research Database, we identified 6284 patients who underwent gastrectomy for GC from 1999 to 2010. In addition, we created a non-DM control cohort consisting of 6268 patients who received gastrectomy during the same period. Compared with the non DM cohort, the DM cohort exhibited a higher prevalence of preoperative coexisting medical conditions, namely hypertension, hyperlipidemia, coronary artery disease, chronic kidney disease, chronic pulmonary disease, stroke, and cirrhosis. The odds ratio (OR) of 30-day postoperative mortality after gastrectomy in the DM cohort was 1.04 (95% confidence interval 0.78-1.40) after we adjusted for covariates. The DM cohort did not exhibit a significantly higher risk of 30-day postoperative morbidities. Further analysis revealed that only patients with a history of a DM-related coma exhibited a higher risk of 30-day postoperative mortality (adjusted OR 2.46, 95% confidence interval 1.10 - 5.54). Moreover, the risk of 90-day postoperative mortality was significantly higher in patients with DM-related eye involvement, coma, peripheral circulatory disease, and renal manifestations, in comparison with the non-DM cohort. The risk of 90-day mortality after gastrectomy for GC is higher in patients with DM-related manifestations than those without DM. PMID- 26376387 TI - Clinical and Immunologic Characteristics of Patients With ANCA-Associated Glomerulonephritis Combined With Membranous Nephropathy: A Retrospective Cohort Study in a Single Chinese Center. AB - The concurrent antineutrophil cytoplasmic antibody-associated glomerulonephritis (ANCA-GN) and membranous nephropathy (MN) have been increasingly documented, mainly in case studies and case series; however, the differences of clinical and pathologic characteristics as well as outcomes between ANCA-GN patients with and without MN remain unclear. The current study investigated the clinical and immunologic features of patients with combined ANCA-GN and MN in a large cohort. Twenty-seven of 223 patients had combined ANCA-GN and MN; they had significantly higher levels of initial serum creatinine, higher Birmingham Vasculitis Activity Score and poorer renal outcome than ANCA-GN patients without MN (P < 0.05). ANCA GN patients with MN could recognize the light chain of myeloperoxidase more frequently than those without MN (P < 0.05). The prevalence of circulating anti PLA2R antibodies and glomerular PLA2R deposits was significantly lower in patients with combined ANCA-GN and MN than that in patients with idiopathic MN (P < 0.05). Compared with the idiopathic MN patients, the patients with combined ANCA-GN and MN had significantly higher recognition frequency of immunoglobulin (Ig) G2 and IgG3, and significantly lower recognition frequency of IgG4 (P < 0.05). Patients with combined ANCA-GN and MN had distinct clinical features and a different pathogenesis of MN. PMID- 26376388 TI - Quality Control and Validation of Oscillometric Blood Pressure Measurements Taken During an Epidemiological Investigation. AB - This study aims to validate blood pressure (BP) values measured by an oscillometric BP monitor and seek possible calibration methods if discrepancies exist. Noninvasive BP measurement outcomes were determined using an oscillometric BP monitor (Omron HBP-1300) versus a mercury sphygmomanometer (standard device). Two percent of subjects enrolled in an epidemiological investigation were systematically sampled in this study. Intraclass correlation coefficient (ICC) was used to evaluate measurement reliability, paired t-test was used to evaluate trueness, and linear regression was used for calibration. The Association for the Advancement of Medical Instrumentation (AAMI) standards and British Hypertension Society (BHS) protocols were used for validation quality assessment. Both mercury sphygmomanometer (standard device) and oscillometric BP monitor (test device) displayed high reliability. A significant difference in systolic blood pressure (SBP) was observed between devices. SBP calibration was achieved by using an effective linear regression model (B = 0.803 and constant = 19.592, P < 0.001). The calibrated model was corroborated by verification samples (P = 0.120) and was found to pass AAMI standards and BHS protocol requirements. Calibrated SBP measurements from the Omron HBP-1300 device were valid. Use of a combination of statistical methods, such as ICC for reliability assessment as well as paired t test for trueness evaluation can be used to validate data from the oscillometric BP monitors. PMID- 26376389 TI - Modified Ilioinguinal Approach to Treat Pelvic or Acetabular Fractures: A Retrospective Study. AB - The aim of this study was to evaluate the potential advantages and clinical results of a modified minimally invasive ilioinguinal approach for the treatment of acetabular or pelvic fractures to the results obtained using a standard ilioinguinal approach. Forty-six patients who were diagnosed as having anterior column acetabular fractures or anterior pelvic ring fractures underwent open reduction and internal fixation through 2 different surgical approaches between June 2008 to June 2012 in our trauma center was studied. The modified ilioinguinal group included 20 patients and the other 26 patients were in the standard ilioinguinal approach group. The clinical and radiographic results were recorded and compared between the 2 groups. There were no significant differences between 2 groups in the mean age, sex, fractures type, and causes of acetabular or pelvic fractures. The mean blood loss in the modified group was 560.0 +/- 57.3 mL versus 850.0 +/- 59.0 mL in the standard ilioinguinal group. The operative time was significantly reduced with modified ilioinguinal approach (86.0 +/- 4.56 min vs. 101.9 +/- 5.38 min). The mean hospital stay was 16.8 +/- 0.58 days and 18.7 +/- 0.52 days in the modified and standard ilioinguinal groups, respectively. According to the Matta score, the quality of reduction between the 2 groups was not significantly different. The complication rate was low in the modified group but not significantly different between the 2 groups. Forty-two patients were followed up with clinical examination and radiographs at a mean of 15.2 months. Solid union was observed in 42 cases at a mean time of 14.8 weeks. The mean Harris Hip Score and the Majeed scores at the time of evaluation were not significantly different between the 2 groups. On comparing the 2 surgical ilioinguinal approaches, it was found that using modified ilioinguinal approach decreased operative time and blood loss, and did not affect the quality of fracture reduction and fracture healing. This study demonstrates that the modified ilioinguinal approach is a simple and minimally invasive approach for anterior column acetabular fractures and pubic rami fractures comparing with the standard ilioinguinal approach. PMID- 26376390 TI - Feasibility of C2 Vertebra Screws Placement in Patient With Occipitalization of Atlas: A Tomographic Study. AB - Occipitalization of atlas (OA) is a congenital disease with the possibility of anomalous bony anatomies and the C2 pedicle screw insertion is technically challenging. However, there are no existing literatures clarified the dimensions and angulations of the C2 pedicles, lamina and lateral masses for screw insertion in patients with OA. Therefore, the aim of this study was to assess the morphometric features of C2 for screw placement in OA to guide the use of surgical screws. Measurements of the OA patients on the computer tomography (CT) images including lamina angle, length and thickness, pedicle angle, length and thickness, and lateral mass thickness and length of the axis vertebra. The OA patients data were compared with age and gender matched cohort of randomly selected patients in a control group without OA. The picture archiving and communication system was used for all patients who had received cervical CT scanning between January 2001 and January 2015. Measurements were performed independently by 2 experienced observers who reviewed the CT scans and recorded the patients with OA. Statistical analysis was performed at a level of significance P < 0.05. A total of 73 patients (29 males and 44 females) were eligible to be included in the OA group. In most of the measurements the pathological cohort had significantly smaller values compared to the control group (P < 0.05). In the OA group, only 45% of the pedicles and 88% of the lamina had thicknesses bigger than 3.5 mm. Both groups had all pedicle and lamina lengths bigger than 12 mm. Regarding the length of the lateral mass, no value was bigger than 12 mm in the OA group, whereas 40% of the values in the control group were bigger than 12 mm. The average pedicle and laminar angles were 37 degrees and 49 degrees in the patients with OA, respectively. The variable anatomy in patients with OA needs to be taken into account when performing spinal stabilization as the C2 bony architectures are significantly smaller than normal. Anatomically, translaminar screw is a more viable option in comparison with pedicle screw for C2 fixation in OA. Nevertheless, the suitability should be fully assessed prior to surgery. PMID- 26376391 TI - Plasma Metanephrines Are Associated With Glucose Metabolism in Patients With Essential Hypertension. AB - There is a high incidence of glucose intolerance in essential hypertension. Overactivation of the sympathetic system is one of important causes of essential hypertension. Whether sympathetic system affects glucose metabolism in patients with essential hypertension has never been reported previously. The aim of this study was to explore the association between the sympathetic system activity and glucose metabolism in patients with essential hypertension. A total of 202 essential hypertension inpatients without diabetes were recruited from Shanghai Ruijin Hospital between February 2006 and August 2013. Activity of sympathetic system was quantified by plasma metanephrines (MNs) levels. All subjects received an oral glucose tolerance test. Fasting plasma glucose and 2-hour plasma glucose increased significantly across the quartiles of plasma MNs. The multiple linear regression analysis revealed that plasma MNs were significantly associated with fasting plasma glucose and 2-hour plasma glucose. The area under curve of plasma glucose increased significantly from the lowest plasma MNs quartile across to the highest quartile. The multiple logistic regression analysis revealed that odds ratios (95% confidence interval) for prediabetes in the highest quartile compared with the lowest quartile of plasma MNs was 4.00 (95% confidence interval, 1.16 13.86). Plasma MNs levels are positively associated with plasma glucose in patients with essential hypertension. Patients with high plasma MNs levels had an increased risk of prediabetes. PMID- 26376392 TI - Analyzing the Relationship Between Bus Pollution Policies and Morbidity Using a Quasi-Experiment. AB - Transit buses are used by millions of commuters every day, but they emit toxic diesel fumes. In 1988, the U.S. Environmental Protection Agency implemented emission standards for transit buses, which have been continually updated. Yet there is no quantitative evidence of the health benefits from these bus pollution policies due to data constraints and confounding variables. In this study, a quasi-experiment is used to exploit the geographic and temporal variation in emission standards by using bus vintage as a proxy for bus emissions. This is accomplished using a unique, rich panel data set, which includes daily information on bus vintage and route for the New York City Transit bus fleet between 2006 and 2009. This information is merged with daily data on emergency department (ED) visits for respiratory illnesses, which include patients' residences at the census block level and exact admission date. Economic benefits resulting from these bus pollution policies are then estimated. Results show that stricter transit bus emission standards by the U.S. Environmental Protection Agency for particulate matter are associated with reduced ED visits for respiratory diseases for patients living within a few hundred feet of a bus route. These findings demonstrate that bus pollution policies have made critical improvements to public health. PMID- 26376393 TI - A Bamboo Joint-Like Appearance is a Characteristic Finding in the Upper Gastrointestinal Tract of Crohn's Disease Patients: A Case-Control Study. AB - The clinical importance of Crohn's disease (CD)-specific lesions in the upper gastrointestinal tract (upper GIT) has not been sufficiently established. The aim of this case-control study is to investigate the characteristic findings of CD in the upper GIT. In 2740 patients who underwent gastroduodenoscopy at Asahikawa Medical University between April 2011 and December 2012, 81 CD patients, 81 gender- and age-matched non-IBD patients, and 66 ulcerative colitis (UC) patients were investigated in the present study. (1) The diagnostic ability and odds ratio of each endoscopic finding (a bamboo joint-like appearance in the cardia, erosions, and/or ulcers in the antrum, notched signs, and erosions and/or ulcers in the duodenum) were compared between the CD and non-IBD patients or UC patients. (2) The interobserver agreement of the diagnosis based on the endoscopic findings was evaluated by 3 experienced and 3 less-experienced endoscopists. The incidence of detecting a bamboo joint-like appearance, notched signs, and erosions and/or ulcers in the duodenum was significantly higher in the CD patients than in the non-IBD and UC patients. In addition, the diagnostic ability and odds ratio of a bamboo joint-like appearance for CD were higher than those for the other findings. Kendall's coefficients of concordance in the group of experienced and less-experienced endoscopists were relatively high for a bamboo joint-like appearance (0.748 and 0.692, respectively). A cardiac bamboo joint-like appearance is a useful finding for identifying high-risk groups of CD patients using only gastroduodenoscopy. PMID- 26376394 TI - Pretreatment Serum Lactate Dehydrogenase and N Classification Predict Long-Term Survival and Distant Metastasis in Patients With Nasopharyngeal Carcinoma Who Have A Positive Family History of Cancer. AB - The purpose of the present study was to evaluate prognostic factors in patients with nasopharyngeal carcinoma (NPC) from the endemic area of southern China who have a positive family history (FH) of cancer. Retrospective analysis of 600 patients with nondisseminated NPC and a positive FH was conducted. The prognostic value of different factors for overall survival (OS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and local relapse-free survival (LRFS) were assessed using Cox regression models. The 3-year OS, DMFS, DFS, and LRFS rates were 93.8%, 91.3%, 86.3%, and 93.8%, respectively. The FH tumor type was NPC for 226/600 (37.7%) patients and other cancers for 374/600 (62.3%) patients. The 3-year OS and DMFS rates for patients with an FH of NPC were 91.2% and 89.8%, respectively. Thirty of 600 (5.0%) patients had elevated pretreatment serum lactate dehydrogenase (LDH >245.0 IU/L). In multivariate analysis, N classification (HR 4.56, 95% CI 2.13-9.74, P < 0.0001) and elevated pretreatment serum LDH (HR 2.87, 95% CI 1.08-7.62, P = 0.034) were independent prognosticators for OS. Female patients (HR 0.42, 95% CI 0.19-0.95, P = 0.037) and patients with normal pretreatment serum LDH (HR 2.42, 95% CI 1.02-5.78, P = 0.046) had better DMFS. Elevated pretreatment serum LDH and N classification are independent prognostic factors for poorer survival in patients with NPC who have a positive FH of cancer. PMID- 26376395 TI - Hereditary Pancreatitis Associated With the N29T Mutation of the PRSS1 Gene in a Brazilian Family: A Case-Control Study. AB - Hereditary pancreatitis (HP) is an autosomal-dominant disease with incomplete penetrance manifesting as early-onset chronic relapsing pancreatitis. A mutation in the PRSS1 gene is present in greater than 70% of HP kindreds and leads to a gain-of-function characterized by the increased autocatalytic conversion of trypsinogen to active trypsin, promoting autodigestion and damage to acinar cells. Other genetic defects observed in the pathogenic mechanism of pancreatitis include mutations in the genes encoding SPINK1, CTRC, and CPA1. There are few reports of HP in Latin America, and no families have been investigated in Brazil. A case-control observational study was conducted at Clementino Fraga Filho University Hospital in Brazil. Patients with suspected HP and healthy controls were enrolled in this study, and a detailed questionnaire was administered to patients with HP. PRSS1 and SPINK1 genes were analyzed by DNA sequencing, and a family that fit the HP diagnostic criteria was identified. The neutral polymorphism c.88-352A > G in the SPINK1 gene was found to be prevalent in the individuals studied, but no important alterations were found in this gene. Ten out of 16 individuals in this family carried the N29T mutation in the PRSS1 gene, with 2 clinically unaffected mutation carriers. The median age of HP onset was 6 years. Pancreatic exocrine failure occurred in 6 patients, 5 of whom also had diabetes mellitus. Surgical procedures were performed on 3 affected members, and no cases of pancreatic cancer have been reported thus far. This study identified the first PRSS1 gene mutation in a Brazilian family with HP. PMID- 26376396 TI - Apex-to-Cupola Distance Following VATS Predicts Recurrence in Patients With Primary Spontaneous Pneumothorax. AB - Our study sought to determine whether the size of the residual apical pleural space in young patients with primary spontaneous pneumothorax (PSP) following video-assisted thoracoscopic surgery is associated with the risk of recurrence. We retrospectively reviewed patients (<=30 years' old) with primary spontaneous pneumothorax following thoracoscopic surgery (2002-2010) in a university affiliated hospital. The size of residual apical pleural space was estimated by measuring the apex-to-cupola distance on a postoperative chest radiograph at 2 time windows: first between postoperative day (POD) 0 and 3, and second between POD 4 and 14. A total of 149 patients were enrolled with a median follow-up of 11.2 months (interquartile range, 0.95-29.5 months), of whom 141 (94.6%) were male with a mean age of 20 years. The postoperative recurrence rate was 11.4%. Comparing the characteristics between the patients with and without recurrent pneumothorax, the patients with recurrence were younger (18.2 + 2.4 vs 20.7 + 3.7 years, P = 0.008), with a lower rate of pleurodesis (35% vs1 69%, P = 0.037), longer apex-to-cupola distance at POD 0 to 3 (22.41 +/- 19.56 vs 10.07 +/- 10.83 mm, P < 0.001) and POD 4 to 14 (11.82 +/- 9.75 vs 5.54 +/- 8.38 mm, P = 0.005) than the patients without recurrence. In a multivariate logistic regression model for recurrent pneumothorax, age <18 years (P = 0.026, odds ratio [OR]: 4.694), apex-to-cupola distance at POD 0 to 3 >10 mm (P = 0.027, OR: 5.319), and no pleurodesis during VATS (P = 0.022, OR: 5.042) were independent risk factors for recurrent pneumothorax. The recurrence rate was not low (11.4%) in young patients with PSP following VATS. Residual apical pleural space with apex-to-cupola distance of 10 mm or greater at POD 0 to 3, younger age, and no pleurodesis would increase postoperative recurrence of primary spontaneous pneumothorax. PMID- 26376397 TI - Intraoperative Dexmedetomidine Promotes Postoperative Analgesia in Patients After Abdominal Colectomy: A Consort-Prospective, Randomized, Controlled Clinical Trial. AB - Surgery-induced acute postoperative pain may lead to prolonged convalescence. The present study was designed to investigate the effects of intraoperative dexmedetomidine on postoperative analgesia following abdominal colectomy surgeries. Eighty patients scheduled for abdominal colectomy surgery under general anesthesia were divided into 2 groups, which were maintained using propofol/remifentanil/dexmedetomidine (PRD) or propofol/remifentanil/saline (PRS). During surgery, patients in the PRD group had a lower bispectral index (BIS) value, which indicated a deeper anesthetic state, and a higher sedation score right after extubation than patients in the PRS group. During the first 24 hours post surgery, PRD patients consumed less morphine in patient-controlled analgesia (PCA) and had a lower score in the visual analog scale (VAS) testing than their controls from the PRS group. Intraoperative administration of dexmedetomidine appears to promote the analgesic property of morphine-based PCA in patients after abdominal colectomy. PMID- 26376398 TI - Multidetector Computed Tomography Features in Differentiating Exophytic Renal Angiomyolipoma from Retroperitoneal Liposarcoma: A Strobe-Compliant Observational Study. AB - This study aims to evaluate the multidetector computed tomography (CT) imaging features in differentiating exophytic renal angiomyolipoma (AML) from retroperitoneal liposarcoma. We retrospectively enrolled 42 patients with confirmed exophytic renal AML (31 patients) or retroperitoneal liposarcoma (11 patients) during 8 years period to assess: renal parenchymal defect at site of tumor contact, supply from branches of renal artery, tumoral vessel extending through the renal parenchyma, dilated intratumoral vessels, hemorrhage, non-fat containing intratumoral nodules with postcontrast enhancement, calcification, renal sinus enlargement, anterior displacement of kidneys, and other associated AML. Renal parenchymal defect, renal arterial blood supply, tumoral vessel through the renal parenchyma, dilated intratumoral vessels, intratumoral/perirenal hemorrhage, renal sinus enlargement, and associated AML were seen only or mainly in exophytic renal AML (all P value < 0.05); however, non-fat-attenuating enhancing intratumoral nodules, intratumoral calcification, and anterior displacement of the kidney were more common in liposarcoma (all P value < 0.05). AMLs reveal renal parenchymal defect at the site of tumor contact, supply from renal artery, tumoral vessel extending through the renal parenchyma, dilated intratumoral vessels, intratumoral and/or perirenal hemorrhage, renal sinus enlargement, and associated AML. Non-fat-attenuating enhancing intratumoral nodules, intratumoral calcifications, and anterior displacement of kidney were more commonly seen in liposarcoma. PMID- 26376399 TI - Reproducibility of Dynamic Contrast-Enhanced MRI in Renal Cell Carcinoma: A Prospective Analysis on Intra- and Interobserver and Scan-Rescan Performance of Pharmacokinetic Parameters. AB - The objective of this study was to investigate the intra- and interobserver as well as scan-rescan reproducibility of quantitative parameters of renal cell carcinomas (RCCs) with dynamic contrast-enhanced magnetic resonance imaging (DCE MRI). A total of 21 patients with clear cell RCCs (17 men, 4 woman; age 37-69 years, mean age 54.6 years, mean size, 5.0 +/- 2.2 cm) were prospectively recruited from September 2012 to November 2012. Patients underwent paired DCE-MRI studies on a 3.0 T MR system with an interval of 48 to 72 hours. The extended Tofts model and population-based arterial input function were used to calculate kinetic parameters. Three observers defined the 2-dimensional whole-tumor region of interest at the slice with the maximum diameter of the RCC. Intraobserver and scan-rescan differences were assessed using paired t tests, whereas interobserver differences using two-way analysis of variance. Intra- and interobserver reproducibility and scan-rescan reproducibility were evaluated using within subject coefficient of variation (wCoV) and intraclass correlation coefficient (ICC). There were no significant intra-, interobserver, or scan-rescan differences in parameters (all P > 0.05). All ICCs for intra- and interobserver agreements were >0.75 (P < 0.05), whereas the scan-rescan agreement was moderate to good; V(e) (0.764, 95% confidence interval [CI]: 0.378-0.925) and K(ep) (0.906, 95% CI: 0.710-0.972) had higher ICC than K(trans) (0.686; 95% CI: 0.212 0.898) and V(p) (0.657; 95% CI: 0.164-0.888). In intra- and interobserver variability analyses, all parameters except V(p) had low wCoV values. K(trans) and V(e) had slightly lower intraobserver wCoV (1.2% and 0.9%) compared with K(ep) (3.7%), whereas all 3 of these parameters had similar interobserver wCoV values (2.5%, 3.1%, and 2.9%, respectively). Regarding scan-rescan variability, K(trans) and K(ep) showed slightly higher variation (15.6% and 15.4%) than V(e) (10.1%). V(p) had the largest wCoV in all variability analyses (all >30%). DCE MRI demonstrated good intra- and interobserver reproducibility and moderate to good scan-rescan performance in the assessment of RCC using K(trans), K(ep), and V(e) as parameters under noncontinuous scanning mode. V(p) showed poor reproducibility, and thus may not be suitable for this scanning protocol. PMID- 26376400 TI - Successful Pregnancy Following Assisted Reproduction in Woman With Systemic Lupus Erythematosus and Hypertension: A Case Report. AB - Patients with systemic lupus erythematosus have a poor prognosis of pregnancy, since it is associated with significant maternal and fetal morbidity, including spontaneous miscarriage, pre-eclampsia, intrauterine growth restriction, fetal death and pre-term delivery. We report a case with successful pregnancy in a patient with systemic lupus erythematosus and hypertension. A 39-year-old nulliparous woman presented with systemic lupus erythematosus with antinuclear and antiphospholipid antibodies, hypertension and recurrent pregnancy loss presented for assisted reproduction. The patient responded well to enoxaparin and prednisone during both assisted reproduction and prenatal treatment. This case report indicates that prescription of immunosuppressant and blood thinners can be safely recommended throughout the whole prenatal period in patients with systemic lupus erythematosus. Enoxaparin and prednisone may be prescribed concurrently during pregnancy. PMID- 26376401 TI - The Incidence of New Vertebral Fractures Following Vertebral Augmentation: A Meta Analysis of Randomized Controlled Trials. AB - A meta-analysis of randomized controlled trials was performed that compares the relationship between percutaneous vertebral augmentation (PVA) and conservative treatments with the incidence of new vertebral fractures. Using meta-analytic techniques, this study compares PVA and conservative treatment for incidence of new vertebral fractures, particularly incidence of adjacent fractures that occur following treatment.A focus of clinicians has been on whether PVA increases the risk of new vertebral fractures. Pubmed, EMBASE, and the Cochrane Central Register of Controlled Trials were searched to retrieve literature published from the establishment of the databases until April 28, 2015. Literature of related areas was searched manually. The main outcome indicator was the incidence of new vertebral fractures at final follow-up appointment. In addition, we evaluated the incidence of new vertebral fractures in different follow-up periods and the incidence of adjacent fractures. The RevMan 5.3 software program of the Cochrane Collaboration was used to analyze the data. For dichotomous variables, the risk ratio (RR) and a confidence interval (CI) of 95% were used to express the heterogeneity of the effect size. Seven randomized controlled trial studies were selected from the literature. The studies include 871 patients, 436 of whom received PVA treatment and the rest received conservative treatment. Combined analysis of the 7 studies showed that the numbers of new vertebral fractures in the 2 groups are not significantly different. Six studies reported the numbers of new adjacent fractures. Considering the heterogeneity among the studies, 2 subgroups were formed. The 5 studies in the European group showed that the incidence of new adjacent fractures in the PVA-treated group is higher than that in the conservatively treated group, and the difference is statistically significant. The one study in the Asian group showed no significant difference between the incidences of adjacent fractures in the 2 groups. PVA treatment does not increase the incidence of new vertebral fractures. Most studies reported that PVA increases the incidence of adjacent fractures, yet it is rarely stated that both PVA and conservative treatment lead to the same incidence of adjacent fractures. PMID- 26376403 TI - Heart Failure and Main Pulmonary Artery Obstruction Caused by Right Ventricular Metastatic Adult Hepatoblastoma: A Case Report. AB - We report a case of a 18-year-old boy who presented with dyspnea and right upper quadrant abdominal dull pain. According to urgent echocardiography, a dense sessile mass occupied the right ventricule. Tumor resection was performed, followed by further adjuvant therapy. The specimen was histopathologically investigated and eventually diagnosed as metastatic adult hepatoblastoma. We discuss its clinical features and treatment in the light of the current knowledge. It is important for us to be aware that adjuvant chemotherapy might be an effective alternative in the treatment of hepatoblastoma combined with ventricle invasion. Early cardiac surgery may be advised in patients with cardiac function impairment. PMID- 26376402 TI - Discriminatory Indices of Typing Methods for Epidemiologic Analysis of Contemporary Staphylococcus aureus Strains. AB - Historically, a number of typing methods have been evaluated for Staphylococcus aureus strain characterization. The emergence of contemporary strains of community-associated S. aureus, and the ensuing epidemic with a predominant strain type (USA300), necessitates re-evaluation of the discriminatory power of these typing methods for discerning molecular epidemiology and transmission dynamics, essential to investigations of hospital and community outbreaks. We compared the discriminatory index of 5 typing methods for contemporary S. aureus strain characterization. Children presenting to St. Louis Children's Hospital and community pediatric practices in St. Louis, Missouri (MO), with community associated S. aureus infections were enrolled. Repetitive sequence-based PCR (repPCR), pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), staphylococcal protein A (spa), and staphylococcal cassette chromosome (SCC) mec typing were performed on 200 S. aureus isolates. The discriminatory index of each method was calculated using the standard formula for this metric, where a value of 1 is highly discriminatory and a value of 0 is not discriminatory. Overall, we identified 26 distinct strain types by repPCR, 17 strain types by PFGE, 30 strain types by MLST, 68 strain types by spa typing, and 5 strain types by SCCmec typing. RepPCR had the highest discriminatory index (D) of all methods (D = 0.88), followed by spa typing (D = 0.87), MLST (D = 0.84), PFGE (D = 0.76), and SCCmec typing (D = 0.60). The method with the highest D among MRSA isolates was repPCR (D = 0.64) followed by spa typing (D = 0.45) and MLST (D = 0.44). The method with the highest D among MSSA isolates was spa typing (D = 0.98), followed by MLST (D = 0.93), repPCR (D = 0.92), and PFGE (D = 0.89). Among isolates designated USA300 by PFGE, repPCR was most discriminatory, with 10 distinct strain types identified (D = 0.63). We identified 45 MRSA isolates which were classified as identical by PFGE, MLST, spa typing, and SCCmec typing (USA300, ST8, t008, SCCmec IV, respectively); within this collection, there were 5 distinct strain types identified by repPCR. The typing methods yielded comparable discriminatory power for S. aureus characterization overall; when discriminating among USA300 isolates, repPCR retained the highest discriminatory power. This property is advantageous for investigations conducted in the era of contemporary S. aureus infections. PMID- 26376405 TI - First Case Report of a Sporadic Adrenocortical Carcinoma With Gastric Metastasis and a Synchronous Gastrointestinal Stromal Tumor of the Stomach. AB - Adrenocortical carcinoma is a rare tumor with high aggresivity that can associate systemic metastases. A 71-year-old man was hospitalized for gastric cancer. The abdominal computed tomography also revealed a tumor above the right kidney. Total gastrectomy and right adrenalectomy were performed. The encapsulated tumor of the adrenal gland weighed 560 grams and presented diffuse tumor architecture under microscope, with capsular, sinusoidal, and vascular invasion. The large tumor cells had a polygonal shape, with slight basophilic, eosinophilic, or vacuolated cytoplasm, pleomorphic nuclei, and a high mitotic rate. In the stomach, the protruded tumor was covered by normal mucosa; under microscope, the tumor cells were observed only in the submucosal layer. In primary adrenal tumor and gastric metastasis the tumor cells were marked by vimentin, inhibin, synaptophysin, neuron-specific enolase, and calretinin. Based on these criteria, the diagnosis of adrenocortical carcinoma (ACC) with gastric metastasis and no lymph node metastases was established. A synchronous 10 * 10-mm-sized gastrointestinal stromal tumor (GIST) of the stomach, without mitoses, was also identified. So far, as we know, this is the 15th case of ever reported synchronous/metachronous sporadic ACCs; the ACC-related gastric metastases either synchronous ACC and GIST, has not been reported in the literature previously. PMID- 26376404 TI - Different Scoring Methods of FDG PET/CT in Giant Cell Arteritis: Need for Standardization. AB - Giant cell arteritis (GCA) is the most frequent form of vasculitis in persons older than 50 years. Cranial and systemic large vessels can be involved. [18F] fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) is increasingly used to diagnose inflammation of the large arteries in GCA. Unfortunately, no consensus exists on the preferred scoring method. In the present study, we aim to define the optimal FDG PET/CT scoring method for GCA diagnosis using temporal artery biopsy and clinical diagnosis as the reference method. FDG PET/CT scans of GCA patients (12 glucocorticoid-naive, 6 on glucocorticoid treatment) and 3 control groups (inflammatory, atherosclerotic, and normal controls) were evaluated. We compared 2 qualitative visual methods (i.e. (1a) first impression and (1b) vascular uptake versus liver uptake) and 4 semiquantitative methods ((2a) SUVmax aorta, (2b) SUVmax aorta-to-liver ratio, (2c) SUVmax aorta-to-superior-caval-vein ratio, and (2d) SUVmax aorta-to-inferior caval-vein ratio). FDG uptake pattern (diffuse or focal) and presence of arterial calcifications were also scored. Diagnostic accuracy of the visual method vascular versus liver uptake (1b) was highest when the cut-off point "vascular uptake higher than liver uptake" (sensitivity 83%, specificity 91%) was used. Sensitivity increased to 92% when patients on glucocorticoids were excluded from the analysis. Regarding the semiquantitative methods, the aorta-to-liver ratio (2b) with a cutoff of 1.03 had the highest diagnostic accuracy, with a sensitivity and specificity of 69% and 92%, respectively. Sensitivity increased to 90% when patients on glucocorticoids were excluded. The number of vascular segments with diffuse FDG uptake pattern was significantly higher in GCA patients without glucocorticoid use compared with all control patient groups. CRP was not significantly different between positive and negative FDG PET scans in the GCA group. Visual vascular uptake higher than liver uptake resulted in the highest diagnostic accuracy for the detection of GCA, especially in combination with a diffuse FDG uptake pattern. Of the semiquantitative methods, the aorta-to-liver SUVmax ratio (cutoff point = 1.03) had the highest diagnostic accuracy. The diagnostic accuracy increased when patients using glucocorticoids were excluded from the analyses. PMID- 26376406 TI - Interhemispheric Connectivity in Drug-Naive Benign Childhood Epilepsy With Centrotemporal Spikes: Combining Function and Diffusion MRI. AB - Decreased intelligence quotients (IQ) have been consistently reported in drug naive benign childhood epilepsy with centrotemporal spikes (BECTS). We aimed to identify the neurophysiological basis of IQ deficits by studying interhemispheric and anatomical functional connectivity in BECTS patients. Resting-state functional and structural magnetic resonance images were acquired in 32 children with BECTS and 25 healthy controls. The IQ was estimated using Wechsler Intelligence Scale for Children China-Revised. The functional connectivity between bilateral homotopic voxels was calculated and compared between groups. Homotopic regions showing abnormal functional connectivity in patients were adopted as regions of interest for analysis by diffusion-tensor imaging tractography. The fractional anisotropy, fiber length, and fiber number were compared between groups. Abnormal homotopic connectivities were correlated with IQ in BECTS patients. Compared with control subjects, patients showed decreased IQ, and decreased voxel-mirrored homotopic connectivity (VMHC) in the bilateral frontal lobule and cerebellum. The performance and full scale IQ significantly increased with the VMHC strength of the middle frontal gyrus (MFG) in controls but not in BECTS patients. A significant negative correlation was observed between VMHC in the premotor cortex and disease duration. Microstructural features within white matter tracts connecting functionally abnormal regions did not reveal any differences between groups. This study provides preliminary evidence for the disrupted functional cooperation between hemispheres in children with BECTS. The findings suggest that the hyposynchrony between the bilateral MFG may be involved in the decreased IQ of BECTS patients. PMID- 26376407 TI - Association of Lifestyle-Related Comorbidities With Periodontitis: A Nationwide Cohort Study in Korea. AB - The aim of this study was to determine the association of periodontitis with lifestyle-related comorbidities (LCs) using data in the Korean National Health Insurance Cohort Database from 2002 to 2013. This was a retrospective study involving a large national cohort with patient samples (representing 2% of the total Korean population) stratified on the basis of sociodemographic information. Using this precisely extracted database, the correlations between LCs (cerebral infarction, angina pectoris, myocardial infarction, hypertension, diabetes mellitus, rheumatoid arthritis, erectile dysfunction, osteoporosis, and obesity) and periodontitis were investigated while adjusting for confounding bias. Univariate and multiple logistic regression analyses were used to evaluate differences in variable factors. Among a total of 1,025,340 samples, 321,103 (31.3%) cases were diagnosed with periodontitis. Statistically significant associations were found between all LCs except myocardial infarction and periodontitis (P < 0.005). Periodontitis is significantly and positively correlated with LCs (except for myocardial infarction) after adjusting for confounding bias. In particular, lifestyle-related diseases, erectile dysfunction, and osteoporosis seem to be intimately related to periodontitis. PMID- 26376408 TI - Association Between Benzodiazepine Use and Epilepsy Occurrence: A Nationwide Population-Based Case-Control Study. AB - We conducted a retrospective case-control study to evaluate the association between the risk of benzodiazepine (BZD) use and epilepsy occurrence by using data from the Taiwan National Health Insurance Research Database. We recruited 1065 participants who ages 20 years or older and newly diagnosed with epilepsy (International Classification of Diseases, Ninth Revision, Clinical Modification 345) between 2004 and 2011 and assigned them to the epilepsy group. We subsequently frequency-matched them with participants in a control group (n = 4260) according to sex, age, and index year at a 1:4 ratio. A logistic regression model was employed to calculate the odds ratio (OR) for association of epilepsy with BZD exposure. Multivariate logistic regression was conducted to estimate the dose-response relationship between BZD levels and epilepsy risk. The adjusted OR (aOR) for the association of epilepsy with BZD exposure was 2.02 (95% confidence interval [CI] = 1.68-2.42). The aOR for an average BZD dose increased to 1.26 for the participants on <0.01 defined daily dose (DDD), and increased to 4.32 for those on >=1.50 DDD. On average, when the DDD of BZD exposure increased by 100 units, the epilepsy risk increase by 1.03-fold (95% CI = 1.01-1.04, P = 0.003). The annual BZD exposure day ranges were significantly associated with epilepsy (2 7 days: aOR = 1.67; 8-35 days: aOR = 3.16; and >=35 days: aOR = 5.60). Whenever the annual BZD exposure increased by 30 days, the risk of epilepsy notably increased by 1.03-fold (95% CI = 1.01-1.04, P < 0.001). In addition, users who quit BZD for more than 6 months still exhibited a higher risk of epilepsy than did the non-BZD users. A considerable increase in epilepsy occurrence was observed in ones with BZD use, particularly in those with prolonged use, multiple exposure, and high-dose consumption. PMID- 26376409 TI - Cortical Representation of Afferent Bodily Signals in Borderline Personality Disorder: Neural Correlates and Relationship to Emotional Dysregulation. AB - IMPORTANCE: The ability to perceive and regulate one's own emotions has been tightly linked to the processing of afferent bodily signals (interoception). Thus, disturbed interoception might contribute to the core feature of emotional dysregulation in borderline personality disorder (BPD), as increased levels of depersonalization, body image disturbances, and reduced sensitivity to physical pain suggest poor body awareness in BPD. OBJECTIVE: To determine neural correlates of disturbed body awareness in BPD and its associations with emotional dysregulation and to explore improvements in body awareness with BPD symptom remission. DESIGN, SETTING, AND PARTICIPANTS: Case-control study performed at Heidelberg University Hospital, Heidelberg, Germany. Heartbeat evoked potentials (HEPs), an indicator of the cortical representation of afferent signals from the cardiovascular system, were investigated in 34 medication-free patients with BPD, 31 healthy volunteers, and 17 medication-free patients with BPD in remission. The HEPs were assessed using 5-minute resting-state electroencephalograms and parallel electrocardiograms. Core BPD symptoms, history of childhood traumatization, and psychiatric disorders were assessed by means of self-reports and structured interviews. To measure neural correlates of disturbed body awareness, high-resolution T1-weighted structural magnetic resonance imaging scans were collected and analyzed using voxel-based morphometry and region-of interest-based approaches. The study was performed between 2012 and 2014, and data analysis was performed in 2014. MAIN OUTCOMES AND MEASURES: Mean HEP amplitudes in resting-state electroencephalograms and their correlation with self reported emotional dysregulation, as well as with gray matter volume. RESULTS: Patients with BPD had significantly reduced mean HEP amplitudes compared with healthy volunteers (F1,61 = 11.32, P = .001), whereas the mean HEP amplitudes of patients with BDP in remission lie somewhere in between these 2 groups of participants (P > .05). The HEP amplitudes were negatively correlated with emotional dysregulation (R = -0.30, P = .01) and positively associated with gray matter volume in the left anterior insula (R = 0.53, P < .05) and the bilateral dorsal anterior cingulate cortex (R = 0.47, P < .05), 2 structures that have been identified as core regions for interoception. CONCLUSIONS AND RELEVANCE: The results indicate state-dependent deficits in the cortical processing of bodily signals in patients with BPD, which appear to be associated with core features of BPD. The analysis of patients with BPD in remission suggests an improvement in cortical representation of bodily signals with symptom remission. Results recommend the integration of techniques to strengthen bodily awareness in psychotherapeutic interventions of BPD. PMID- 26376410 TI - Genome wide microarray based expression profiles associated with BmNPV resistance and susceptibility in Indian silkworm races of Bombyx mori. AB - The molecular mechanism involved in BmNPV resistance was investigated using a genome wide microarray in midgut tissue of Indian silkworm Bombyx mori. In resistant race (Sarupat), 735 genes up-regulated and 589 genes down-regulated at 12 h post BmNPV infection. Similarly, in case of susceptible race (CSR-2), 2183 genes up-regulated and 2115 genes down-regulated. Among these, nine up-regulated and eight down-regulated genes were validated using real-time qPCR analysis. In Sarupat, vacuolar protein sorting associated, Xfin-like protein and carboxypeptidase E-like protein genes significantly up-regulated in infected midgut; prominently down-regulated genes were glutamate receptor ionotropic kainite 2-like, BTB/POZ domain and transferrin. Considerably up-regulated genes in the CSR-2 were peptidoglycan recognition protein S6 precursor and rapamycin while the conspicuous down-regulated genes were facilitated trehalose transporter and zinc transporter ZIP1-like gene. The up-regulation of genes in resistant race after BmNPV infection indicates their possible role in antiviral immune response. PMID- 26376411 TI - Exposed tibial bone after burns: Flap reconstruction versus dermal substitute. AB - A 44 years old male patient had suffered extensive 3rd degree burns on both legs, undergoing thorough surgical debridement, resulting in both tibias being exposed. Approximately 5 months after the incident he was referred to the Department of Plastic and Reconstructive Surgery of the University Hospital Gent, Belgium, to undergo flap reconstruction. Free flap surgery was performed twice on both lower legs but failed on all four occasions. In between flap surgery, a dermal substitute (Integra((r))) was applied, attempting to cover the exposed tibias with a layer of soft tissue, but also without success. In order to promote the development of granulation tissue over the exposed bone, small holes were drilled in both tibias with removal of the outer layer of the anterior cortex causing the bone to bleed and subsequently negative pressure wound therapy (NPWT) was applied. The limited granulation tissue resulting from this procedure was then covered with a dermal substitute (Glyaderm((r))), consisting of acellular human dermis with an average thickness of 0.25mm. This dermal substitute was combined with a NPWT-dressing, and then served as an extracellular matrix (ECM), guiding the distribution of granulation tissue over the remaining areas of exposed tibial bone. Four days after initial application of Glyaderm((r)) combined with NPWT both tibias were almost completely covered with a thin coating of soft tissue. In order to increase the thickness of this soft tissue cover two additional layers of Glyaderm((r)) were applied at intervals of approximately 1 week. One week after the last Glyaderm((r)) application both wounds were autografted. The combination of an acellular dermal substitute (Glyaderm((r))) with negative pressure wound therapy and skin grafting proved to be an efficient technique to cover a wider area of exposed tibial bone in a patient who was not a candidate for free flap surgery. An overview is also provided of newer and simpler techniques for coverage of exposed bone that could question the universal plastic surgery paradigm that flap surgery is the only way to cover these defects. PMID- 26376412 TI - Regulation of insulin signaling in skeletal muscle by PIP3 phosphatase, SKIP, and endoplasmic reticulum molecular chaperone glucose-regulated protein 78. AB - Insulin resistance is characterized as a pathogenic factor in type 2 diabetes. Despite skeletal muscle being primarily responsible for systemic glucose disposal, the mechanisms underlying the induction of insulin resistance in skeletal muscle have not been fully elucidated. A number of studies have shown that it is characterized by the inhibition of the phosphatidylinositol (PI) 3 kinase signaling pathway. Here, we show that skeletal muscle- and kidney-enriched inositol polyphosphate phosphatase (SKIP), a phosphatidylinositol-3,4,5 trisphosphate (PIP3) phosphatase, and glucose-regulated protein 78 (GRP78) are implicated in the inhibition of insulin-dependent PI 3-kinase signaling in skeletal muscle. Mechanistically, under resting conditions, SKIP forms a complex with GRP78 at the endoplasmic reticulum (ER). Insulin stimulation facilitates the dissociation of SKIP from GRP78 and its binding to the activated form of Pak1. GRP78 is necessary for membrane localization and Pak1-binding of SKIP, which facilitates inactivation of the insulin signaling pathway. These findings underscore the specific and prominent role of SKIP and GRP78 in the regulation of insulin-dependent PI 3-kinase signaling in skeletal muscle. PMID- 26376413 TI - [In Process Citation]. PMID- 26376414 TI - [In Process Citation]. PMID- 26376415 TI - [In Process Citation]. PMID- 26376416 TI - [Diagnosis and treatment of symptomatic hydronephrosis in pregnancy]. AB - Hydronephrosis in pregnancy is common in the second and third trimester. Only a few cases are symptomatic, caused by a ureteric stone or by the pregnancy itself. The clinical dilemma is when to treat and when not to treat. We propose a multidisciplinary management based on renal ultrasonography to verify hydronephrosis and renography to diagnose obstructive hydronephrosis. Obstruction with a high intra-renal pressure must be treated to avoid kidney dysfunction. Patients with pyonephrosis need immediate treatment. PMID- 26376417 TI - [Squamous cell carcinoma developing in necrobiosis lipoidica in a diabetic patient]. AB - The development of squamous cell carcinoma in chronic and/or non-healing ulcers associated with necrobiosis lipoidica (NL) is rare, but should be considered in diabetic patients. NL is a non-infectious granulomatous degenerative skin disease. The prevalence of NL in diabetic patients is estimated to 0,3-1,2%. Awareness of malignant transformation potential within a plaque of NL is crucial for early diagnosis and easy radical treatment. A case from our outpatient diabetes clinic is presented. PMID- 26376418 TI - [A strategic TeleMatch-model can be useful in choosing the right telemedical solution]. AB - This article presents the results of a qualitative, comparative study of three hospital-based telemedical solutions for patients with COPD. Based on an analysis of technological and patient perspectives the paper identifies three parameters that influence the role of the patient and the collaboration between patient and clinician. The article develops a stra-tegic TeleMatch-model that conceptualizes how the planning of patient care paths can be supported by various technologies matching the specific needs of the patient, supporting self-monitoring for those who are able and offering video consultations to vulnerable patients. PMID- 26376419 TI - [Patients with chronic obstructive pulmonary disease and heart disease can benefit from beta-blocker treatment]. AB - Chronic obstructive pulmonary disease (COPD) and coronary heart disease share smoking as the most important common risk factor and there is a high prevalence of cardiovascular disease among COPD patients. Although cardioselective beta blockers are safe in treatment of COPD, they are often withheld in these patients. In observational studies, beta-blocker treatment is associated with significantly reduced mortality and reduced risk of exacerbations of COPD. This effect may be caused by the beneficial effect of beta-blockers on heart failure, tachycardia and upregulation of beta-receptors in the airways. PMID- 26376420 TI - [Congenital central hypoventilation syndrome diagnosed in a two-year-old girl]. AB - Congenital central hypoventilation syndrome (CCHS) is a rare genetic disorder characterized by inadequate response to hypoxia and hypercapnia and life threatening alveolar hypoventilation most pronounced during sleep. It is associated with other disorders of neural crest origin and of autonomic dysfunction. Usually the diagnosis is made in the neonatal period. We describe a case where a two-year-old girl had respiratory failure during the first week of her life and CCHS was suspected, but followed by spontaneous recovery and a two year period without symptoms. PMID- 26376421 TI - [Molecular genetic diagnostics of the cause of ventricular arrhythmias in children]. AB - Andersen-Tawil syndrome (ATS) is a rare hereditary multi--system disorder consisting of a triad of symptoms, ventricular arrhythmias, periodic paralysis and dysmorphic features. The syndrome is associated with a loss of function mutation in the gene KCNJ2, which encodes the Kir2.1 inward rectifier potassium channel. We represent a case story of a 15-year-old girl who had unexplained arrhythmias for six years. Molecular genetic screening with a 75-heart-panel revealed a pathogenic KCNJ2 missense mutation. The patient was diagnosed with ATS. PMID- 26376422 TI - Fluorescent Photochromic Diarylethene That Turns on with Visible Light. AB - A new fluorescent photochromic diarylethene that can be activated by irradiation with 405 nm light was synthesized. The turn-on mode switching of fluorescence with visible light is favorable for application to biological systems. The fluorescence quantum yield of the photogenerated closed-ring isomer was as high as 0.8 in less or medium polar solvents, and even in polar acetonitrile the yield was higher than 0.6. PMID- 26376423 TI - Nucleic acid import into mitochondria: New insights into the translocation pathways. AB - Mitochondria have retained indispensable but limited genetic information and they import both proteins and nucleic acids from the cytosol. RNA import is essential for gene expression and regulation, whereas competence for DNA uptake is likely to contribute to organellar genome dynamics and evolution. Contrary to protein import mechanisms, the way nucleic acids cross the mitochondrial membranes remains poorly understood. Using proteomic, genetic and biochemical approaches with both plant and yeast organelles, we develop here a model for DNA uptake into mitochondria. The first step includes the voltage-dependent anion channel and an outer membrane-located precursor fraction of a protein normally located in the inner membrane. To proceed, the DNA is then potentially recruited in the intermembrane space by an accessible subunit of one of the respiratory chain complexes. Final translocation through the inner membrane remains the most versatile but points to the components considered to make the mitochondrial permeability transition pore. Depending on the size, DNA and RNA cooperate or compete for mitochondrial uptake, which shows that they share import mechanisms. On the other hand, our results imply the existence of more than one route for nucleic acid translocation into mitochondria. PMID- 26376424 TI - Stress, relationship satisfaction, and health among African American women: Genetic moderation of effects. AB - We examined whether romantic relationship satisfaction would serve as a link between early and later stressors which in turn would influence the thyroid function index (TFI), an indicator of physiological stress response. Using the framework of genetic susceptibility theory combined with hypotheses derived from the vulnerability-stress-adaptation and stress-generation models, we tested whether the hypothesized mediational model would be conditioned by 5-HTTLPR genotype, with greater effects and stronger evidence of mediation among carriers of the "s" allele. In a sample of African American women in romantic relationships (n = 270), we found that 5-HTTLPR moderated each stage of the hypothesized mediational model in a "for better or for worse" manner. That is genetic polymorphisms function to exacerbate not only the detrimental impact of negative environments (i.e., "for worse effects") but also the beneficial impact of positive environments (i.e., "for better effects"). The effect of early stress on relationship satisfaction was greater among carriers of the "short" allele than among those who did not carry the short allele, and was significantly different in both the "for better" and "for worse" direction. Likewise, the effect of relationship satisfaction on later stressors was moderated in a "for better "or "for worse" manner. Finally, impact on physiological stress, indexed using TFI level, indicated that the impact of later stressors on TFI level was greater in the presence of the short allele, and also followed a "for better" or "for worse" pattern. As expected, the proposed mediational model provided a better fit for "s" allele carriers. PMID- 26376425 TI - The interplay of couple's shared time, women's intimacy, and intradyadic stress. AB - Theoretically, spending time together should be central for couples to build intimacy and should be associated with less relationship stress; however, few empirical studies have examined these links. The present study used 14 days of diary data from 92 women to investigate the interplay between the amount of time they spent with their partner (shared time), intimacy, and daily stress originating inside the relationship (intradyadic stress) on a within- and between personal level. Multilevel analyses revealed moderation patterns: For example, when women spent more time with their partners than usual on a weekday with low levels of intradyadic stress, they reported higher intimacy. These associations varied substantially between women and were weaker on the weekend or on days with high levels of intradyadic stress. At the between-person level, higher average shared time appeared to buffer the negative association between intradyadic stress and intimacy. Our results suggest that daily fluctuations in intradyadic stress, intimacy, and shared time may have different implications compared with aggregated amounts of those variables. Spending more time together on a weekday with low intimacy might be linked to more intradyadic stress, but aggregated over the long run, spending more time together may provide opportunities for stress resolution and help couples to maintain their intimacy. PMID- 26376426 TI - Examining reciprocal influences among family climate, school attachment, and academic self-regulation: Implications for school success. AB - Guided by family systems and ecological theories, this study examined the multicontextual implications of family, school, and individual domains for adolescents' school success. The first goal of this study was to examine reciprocal influences among family climate, school attachment, and academic self regulation (ASR) during the middle school years. The second goal was to test the relative impact of each of these domains on adolescents' school adjustment and academic achievement after the transition to high school. We applied a cross-lag structural equation modeling approach to longitudinal data from 979 students in the 6th grade and their families, followed over 5 measurement occasions, from 6th through 9th grade. Controlling for family income, parent education, and adolescent gender, the results revealed reciprocal relationships between the family climate and school attachment over time; both of these factors were related to increases in ASR over time. In turn, ASR was a robust predictor of academic success, with unique associations with school adjustment and academic achievement. Family climate and school adjustment had modest to marginal associations with school adjustment, and no association with academic achievement. Applications of these findings for family school interventions are discussed. (PsycINFO Database Record PMID- 26376427 TI - Perceived parental security profiles in African American adolescents involved in the juvenile justice system. AB - Many researchers have shown the importance of parent attachment in childhood and adolescence. The present study extends the attachment literature to African Americans involved in the juvenile justice system (N = 213), and provides an initial inquiry using person-oriented methods. The average age was 16.17 years (SD = 1.44), and the sample was predominantly male (71%). Results of a confirmatory factor analysis of Inventory of Parent and Peer Attachment-Short Form (IPPA-S) scores supported a 3-factor model: (a) Communication, (b) Trust, and (c) Alienation. Model-based clustering was applied to IPPA-S scores, and results pointed to 4 perceived parental security profiles: high security, moderately high security, moderately low security, and low security. In keeping with our hypotheses, IPPA-S profiles were associated with prosocial behaviors, depression, anxiety, and oppositional defiance. Contrary to hypotheses, IPPA-S profiles were not associated with perspective taking, emotional concern, or behaviors characteristic of a conduct disorder. Results also showed that gender, age, family member with whom the participant resides, charge severity, and offense history did not have an effect on IPPA-S clustering. Implications for therapeutic jurisprudence in African Americans involved with the juvenile justice system are provided. PMID- 26376428 TI - Treatment response in couple therapy: Relationship adjustment and individual functioning change processes. AB - This study, a naturalistic investigation of the process of change in relationship adjustment and individual functioning during conjoint therapy, examined the first 8 sessions of a multisystemic model of couple therapy, integrative problem centered metaframeworks (Breunlin, Pinsof, Russell, & Lebow, 2011; Pinsof, Breunlin, Russell, & Lebow, 2011). The sample consisted of 125 heterosexual couples who reported on their relationship adjustment and individual functioning before every session using the Systemic Therapy Inventory of Change (Pinsof et al., 2009; Pinsof, Zinbarg, et al., in press). Data were analyzed using dyadic latent growth curve and cross-lagged models. For both men and women, relationship adjustment and individual functioning showed nonlinear change, increasing during Sessions 1-4 and stabilizing during Sessions 5-8. At pretreatment, women reported lower levels of relationship adjustment than men; no gender differences existed in initial levels of individual functioning or in the change trajectories of relationship adjustment or individual functioning. Higher relationship adjustment predicted positive change in individual functioning for men (but not for women). In contrast, there were no cross-lagged effects of individual functioning on relationship adjustment for men or women. The results demonstrate the importance of examining the processes by which relational and individual pathology respond to couple-based interventions. PMID- 26376429 TI - Parental emotional competence and parenting in low-income families with adolescents. AB - Ample research has demonstrated that alexithymia, which is characterized by difficulty processing emotions, is associated with disruptions in parenting infants and toddlers. Individuals suffering from alexithymia have among other negative outcomes difficulty building and maintaining interpersonal relationships. Research on emotional expression and recognition has documented the importance of these competencies for the quality of the parent-child relationship and for skills critical for parents of adolescents, such as effective monitoring. However, literature linking parental alexithymia to parenting behaviors and related constructs during adolescents is lacking. The present study closes this gap by examining how mothers' (M age = 39.42 years, SD = 7.62; Range = 23-67) alexithymia affects parent-reported behaviors of solicitation and control, as well as youths' (53.6% female; M age = 12.13 years, SD = 1.62; Range = 9-16) reported disclosure and felt acceptance by their mothers among a sample of 358 primarily urban, African American families. Structural equation models (SEM) revealed that mothers' alexithymia was prospectively related to less parental solicitation 2 years later for both males and females, and to lower levels of felt acceptance for males. Multiple group analyses revealed that these models fits equally well for younger and older youth. Contrary to hypotheses, alexithymia was not related to control or to disclosure. Taken together, these findings indicate that parents' difficulty in processing emotions contributes to parenting beyond early childhood. PMID- 26376430 TI - Idiopathic Chronic Parotitis: Imaging Findings and Sialendoscopic Response. AB - BACKGROUND/AIMS: The purpose of this study was to correlate imaging and sialendoscopic findings to therapeutic response in patients with idiopathic chronic parotitis. METHODS: We retrospectively reviewed 122 consecutive sialendoscopies performed in an academic medical center by two surgeons between 2008 and 2013. Forty-one (34%) and 54 (44%) patients were excluded on the basis of having parotid or submandibular sialolith, respectively. Nineteen cases were included in the study with idiopathic chronic parotitis. There was a median follow-up of 5 months. RESULTS: Computed tomography (CT) imaging had a sensitivity and specificity of 80.0 and 71.4%, respectively, for predicting abnormal findings on sialendoscopy, while magnetic resonance imaging (MRI) had 100% accuracy in a small set of cases. In glands with noticeable pathology present on preoperative imaging or sialendoscopy, 11 out of 12 glands (92%) treated experienced symptomatic improvement, while 3 out of 7 glands (43%) without pathology on imaging or endoscopy experienced symptomatic improvement (p = 0.038). CONCLUSIONS: Sialendoscopy for the treatment of idiopathic chronic parotid disease can improve pain and swelling with a higher frequency of success in patients with abnormalities noted on endoscopy. CT and MRI have a moderate degree of accuracy in predicting which patients will benefit from therapeutic sialendoscopy. PMID- 26376431 TI - Encountering extreme weather during migration: individual strategies and their consequences. AB - The way that animal populations respond to changing weather conditions is a major focus of current research, fuelled by the need to predict the future consequences of climatic changes. Severe weather events can provide valuable opportunities to uncover the mechanisms through which the weather influences population demography but opportunities to track individual responses to such events are rare. Senner et al. (2015) report on an exceptional opportunity to address this issue, when their detailed studies of a migratory shorebird population were interrupted by an extreme weather event that coincided with spring migration, a key period in the annual cycle of migratory species. Through tracking of individuals across the migratory range, Senner et al. (2015) show that, while individual schedules were severely disrupted by the harsh weather, with many individuals undertaking reverse migrations and experiencing delayed breeding, breeding success was unaffected. This study highlights the complexities involved in predicting the ecological consequences of extreme weather events and the key role of behavioural flexibility in mitigating the costs to individuals. PMID- 26376432 TI - A Sweetpotato Geranylgeranyl Pyrophosphate Synthase Gene, IbGGPS, Increases Carotenoid Content and Enhances Osmotic Stress Tolerance in Arabidopsis thaliana. AB - Sweetpotato highly produces carotenoids in storage roots. In this study, a cDNA encoding geranylgeranyl phyrophosphate synthase (GGPS), named IbGGPS, was isolated from sweetpotato storage roots. Green fluorescent protein (GFP) was fused to the C-terminus of IbGGPS to obtain an IbGGPS-GFP fusion protein that was transiently expressed in both epidermal cells of onion and leaves of tobacco. Confocal microscopic analysis determined that the IbGGPS-GFP protein was localized to specific areas of the plasma membrane of onion and chloroplasts in tobacco leaves. The coding region of IbGGPS was cloned into a binary vector under the control of 35S promoter and then transformed into Arabidopsis thaliana to obtain transgenic plants. High performance liquid chromatography (HPLC) analysis showed a significant increase of total carotenoids in transgenic plants. The seeds of transgenic and wild-type plants were germinated on an agar medium supplemented with polyethylene glycol (PEG). Transgenic seedlings grew significantly longer roots than wild-type ones did. Further enzymatic analysis showed an increased activity of superoxide dismutase (SOD) in transgenic seedlings. In addition, the level of malondialdehyde (MDA) was reduced in transgenics. qRT-PCR analysis showed altered expressions of several genes involved in the carotenoid biosynthesis in transgenic plants. These data results indicate that IbGGPS is involved in the biosynthesis of carotenoids in sweetpotato storage roots and likely associated with tolerance to osmotic stress. PMID- 26376433 TI - Variation in Hospital Episode Costs With Bariatric Surgery. AB - IMPORTANCE: Under bundled payment programs, hospitals receive a single payment for all services provided surrounding an episode of care. Because health care providers, such as hospitals and physicians, accept more financial risk under these programs, they will need a better understanding of episode costs to identify areas to target improvements in quality and cost-efficiency. OBJECTIVE: To examine hospital variation in episode costs for a common high-risk procedure that is a prime candidate for bundled payment programs (ie, bariatric surgery). DESIGN, SETTING, AND PARTICIPANTS: In this retrospective cohort study, we used national Medicare claims data and identified patients undergoing bariatric procedures in 2011-2012 (N = 24 647 patients; 463 hospitals). We calculated risk adjusted Medicare payments from the date of admission for the index procedure to 30 days following discharge. We then divided hospitals into equally sized quartiles and examined variation in payments for services around episodes of care. Medicare payments were examined by service payment type (ie, payments to hospitals, payments to physicians, and payments for postacute care services) across hospital quartiles. MAIN OUTCOMES AND MEASURES: Hospital variation in episode costs for services around an episode of bariatric surgery. RESULTS: Mean total payments for bariatric procedures varied from $11 086 to $13 073 per episode of care, resulting in a mean difference of $1987 (16.5% difference) per episode of care between the lowest and highest hospital quartiles. The index hospitalization was responsible for the largest portion of total payments (75%), followed by physician services (21%) and postacute care services (2.8%). Payments for index hospitalization accounted for the greatest variation in payments. CONCLUSIONS AND RELEVANCE: There are variations in hospital episode payments among Medicare patients undergoing bariatric surgery procedures. As hospitals enter bundled payment programs, they will need to target areas with the largest variation in costs for quality- and efficiency-improvement activities. PMID- 26376434 TI - Risk Factors for Polyautoimmunity among Patients with Celiac Disease: A Cross Sectional Survey. AB - AIM: To define the prevalence of polyautoimmunity (PAI) among celiac disease (CD) patients and to compare clinical and laboratory features of CD patients with or without PAI in order to determine the risk factors for PAI in CD. MATERIAL AND METHOD: Patients diagnosed with CD in our clinic between 2007 and 2014 with at least 1 year of follow-up were retrospectively evaluated. Totally 145 patients were included in the study. Information on patient demographics and laboratory data were obtained from patient records. The study participants were divided into 2 groups. Group 1 was the CD-alone group consisting of patients without any other autoimmune diseases (AIDs), while group 2 was the PAI group consisting of patients with accompanying one or more AIDs. RESULTS: The mean age of 145 CD patients (106 female and 39 male) included in the study was 37.2 +/- 12.3 years. Of the 145 patients included, 48 (33.1%) were in the PAI group. When two groups were compared with each other in terms of the demographic features and laboratory data, the following were identified as risk factors for PAI: female gender, family history for AIDs, antigliadin IgG positivity, vitamin D deficiency, antinuclear antibody positivity >=1/80 titer and having any musculoskeletal disease. CONCLUSION: To the best of our knowledge, this is one of the largest studies in the literature on CD patients for the PAI prevalence and related risk factors. Identification of the risk factors in early stages is important to explore PAI among CD patients. Larger, prospective studies are warranted about the risk factors and autoimmune characteristics of CD. PMID- 26376435 TI - Targeting Mortalin by Embelin Causes Activation of Tumor Suppressor p53 and Deactivation of Metastatic Signaling in Human Breast Cancer Cells. AB - Embelin, a natural quinone found in the fruits of Embelia ribes, is commonly used in Ayurvedic home medicine for a variety of therapeutic potentials including anti inflammation, anti-fever, anti-bacteria and anti-cancer. Molecular mechanisms of these activities and cellular targets have not been clarified to-date. We demonstrate that the embelin inhibits mortalin-p53 interactions, and activates p53 protein in tumor cells. We provide bioinformatics, molecular docking and experimental evidence to the binding affinity of embelin with mortalin and p53. Binding of embelin with mortalin/p53 abrogates their complex resulted in nuclear translocation and transcriptional activation function of p53 causing growth arrest in cancer cells. Furthermore, analyses of growth factors and metastatic signaling using antibody membrane array revealed their downregulation in embelin treated cells. We also found that the embelin causes transcriptional attenuation of mortalin and several other proteins involved in metastatic signaling in cancer cells. Based on these molecular dynamics and experimental data, it is concluded that the anticancer activity of embelin involves targeting of mortalin, activation of p53 and inactivation of metastatic signaling. PMID- 26376436 TI - Probiotics Reduce Inflammation in Antiretroviral Treated, HIV-Infected Individuals: Results of the "Probio-HIV" Clinical Trial. AB - BACKGROUND: HIV infection results in damage to the gastrointestinal (GI) tract, microbial translocation and immune activation. These are not completely normalized with combined antiretroviral therapy (cART). Moreover, increate morbidity and mortality of cART-treated HIV-infected individuals is associated with inflammation. METHODS: In order to enhance GI tract immunity, we recruited and treated 20 HIV-infected humans with cART supplemented with probiotics and followed inflammation and immunological parameters (clinical trial number NCT02164344). 11 HIV seronegative subjects were included as control group. The enumeration of CD4+, CD8+, CD38+ and HLA-DR+ lymphocytes were evaluated on peripheral blood; HIV-RNA levels, sCD14, d-dimer, C-reactive protein (CRP) high sensitivity C-reactive protein (hsCRP), IL-6 and Lipopolysaccharide Binding Protein (LBP) were assayed on plasma. RESULTS: We observe that cART does not normalize the levels of immune activation in HIV positive patients anyway inflammation and markers of microbial translocation were significantly reduced with probiotic supplementation. Patients show a clear and statistically significant reduction in the levels of immune activation on CD4 T-lymphocytes, for both markers CD38 and HLA-DR and their simultaneous expression, LBP and hsCRP plasma levels after probiotic diet supplementation settling to values comparable to controls. CONCLUSIONS: Supplementing cART with probiotics in HIV-infected individuals may improve GI tract immunity and there by mitigate inflammatory sequelae, ultimately improving prognosis. TRIAL REGISTRATION: ClinicalTrials.gov NCT02164344. PMID- 26376437 TI - Inconsistency of allometric scaling for dissociative anesthesia of wild felids. AB - OBJECTIVE: To evaluate allometric scaling for ketamine-xylazine (KX) anesthesia in wild felids using domestic cats for reference. STUDY DESIGN: Prospective single-phase non-blinded study. ANIMALS: Six domestic cats and 13 wild felids (five Leopardus pardalis, five Puma concolor, one Panthera onca and two Panthera leo). METHODS: Six domestic cats (4.1 +/- 0.8 kg, REF1) were anesthetized by intramuscular administration of ketamine (15 mg kg(-1) ) and xylazine (1 mg kg( 1) ). Wild cats were divided into three groups based on body weight: 12.9 +/- 2.4 kg (G1; n = 7), 43.0 +/- 15.7 kg (G2; n = 4) and 126.0 +/- 7.8 kg (G3; n = 2). Ketamine and xylazine doses were calculated based on allometric scaling of the basal metabolic rate (BMR = 70 * body mass(0.75) ). Afterwards, the six domestic cats were administered mean KX doses calculated for G1 and G2 (REF2). The heart rate, systolic arterial pressure, respiratory frequency, pH, the venous partial pressure of carbon dioxide, bicarbonate and lactate concentrations were recorded for up to 60 minutes. RESULTS: Additional doses were required in 12 out of the 13 wild cats. Anesthesia was not achieved in G3. Latency periods in wild felids were longer than REF1 and REF2. Anesthesia duration in REF1 was longer than that in the other groups. Recovery from anesthesia in REF1 and REF2 was longer than G1 and G2. Physiological variables remained within the range limits for the species. G1 baseline lactate concentration was higher than in the other groups. CONCLUSION AND CLINICAL RELEVANCE: KX anesthesia established by allometric scaling of BMR from doses administered to domestic cats did not predict reliable anesthetic doses for wild cats. Dose rates calculated with this method must not be applied to these species. PMID- 26376438 TI - Tuberculosis Laboratory Diagnosis Quality Assurance among Public Health Facilities in West Amhara Region, Ethiopia. AB - INTRODUCTION: Reliable smear microscopy is an important component of Directly Observed Treatment Scheme (DOTS) strategy for TB control program in countries with limited resources. Despite external quality assessment is established in Ethiopia, there is lower TB detection rate (48%) in Amhara region compared to the World Health Organization (WHO) estimate (70%). This highlights the quality of smear microscopy needs to be evaluated. Therefore, the aim of this study was to assess the quality of sputum smear microscopy performance among health center laboratories in West Amhara region, Ethiopia. MATERIALS AND METHODS: A cross sectional study was conducted from July 08, 2013 to July 07, 2014. Data were collected from 201 public health center laboratories using a structured questionnaire. Slides were collected based on Lot Quality Assurance Sampling (LQAS) method and rechecked blindly by trained laboratory technologists. The data were entered into EPI info V.7 and smear quality indicators and AFB results were analyzed by SPSS version 20. RESULTS: Among 201 laboratories enrolled in this study, 47 (23.4%) laboratories had major errors. Forty one (20.4%) laboratories had a total of 67 false negative and 29 (14.4%) laboratories had a total of 68 false positive results. Specimen quality, smear thickness and evenness were found poor in 134 (66.7%), 133 (66.2%) and 126 (62.7%) laboratories, respectively. Unavailability of microscope lens cleaning solution (AOR: 2.90; 95% CI: 1.25 6.75; P: 0.013) and dirty smears (AOR: 2.65; 95% CI: 1.14-6.18; P: 0.024) were correlated with false negative results whereas no previous EQA participation (AOR: 3.43; 95% CI: 1. 39-8.45; P: 0.007) was associated with false positive results. CONCLUSION: The performance of health facilities for sputum smear microscopy was relatively poor in West Amhara region. Hence, strengthening the EQA program and technical support on sputum smear microscopy are recommended to ensure quality tuberculosis diagnostic service. PMID- 26376439 TI - The Huge Reduction in Adult Male Mortality in Belarus and Russia: Is It Attributable to Anti-Alcohol Measures? AB - BACKGROUND AND AIM: Harmful alcohol consumption has long been recognized as being the major determinant of male premature mortality in the European countries of the former USSR. Our focus here is on Belarus and Russia, two Slavic countries which continue to suffer enormously from the burden of the harmful consumption of alcohol. However, after a long period of deterioration, mortality trends in these countries have been improving over the past decade. We aim to investigate to what extent the recent declines in adult mortality in Belarus and Russia are attributable to the anti-alcohol measures introduced in these two countries in the 2000s. DATA AND METHODS: We rely on the detailed cause-specific mortality series for the period 1980-2013. Our analysis focuses on the male population, and considers only a limited number of causes of death which we label as being alcohol-related: accidental poisoning by alcohol, liver cirrhosis, ischemic heart diseases, stroke, transportation accidents, and other external causes. For each of these causes we computed age-standardized death rates. The life table decomposition method was used to determine the age groups and the causes of death responsible for changes in life expectancy over time. CONCLUSION: Our results do not lead us to conclude that the schedule of anti-alcohol measures corresponds to the schedule of mortality changes. The continuous reduction in adult male mortality seen in Belarus and Russia cannot be fully explained by the anti alcohol policies implemented in these countries, although these policies likely contributed to the large mortality reductions observed in Belarus and Russia in 2005-2006 and in Belarus in 2012. Thus, the effects of these policies appear to have been modest. We argue that the anti-alcohol measures implemented in Belarus and Russia simply coincided with fluctuations in alcohol-related mortality which originated in the past. If these trends had not been underway already, these huge mortality effects would not have occurred. PMID- 26376440 TI - Correction: OTG-snpcaller: An Optimized Pipeline Based on TMAP and GATK for SNP Calling from Ion Torrent Data. PMID- 26376441 TI - Tuberculous Lymphadenitis in Ethiopia Predominantly Caused by Strains Belonging to the Delhi/CAS Lineage and Newly Identified Ethiopian Clades of the Mycobacterium tuberculosis Complex. AB - BACKGROUND: Recently, newly defined clades of Mycobacterium tuberculosis complex (MTBC) strains, namely Ethiopia 1-3 and Ethiopia H37Rv-like strains, and other clades associated with pulmonary TB (PTB) were identified in Ethiopia. In this study, we investigated whether these new strain types exhibit an increased ability to cause TB lymphadenitis (TBLN) and raised the question, if particular MTBC strains derived from TBLN patients in northern Ethiopia are genetically adapted to their local hosts and/or to the TBLN. METHODS: Genotyping of 196 MTBC strains isolated from TBLN patients was performed by spoligotyping and 24-loci mycobacterial interspersed repetitive unit-variable number of tandem repeats (MIRU-VNTR) typing. A statistical analysis was carried out to see possible associations between patient characteristics and phylogenetic MTBC strain classification. RESULTS: Among 196 isolates, the majority of strains belonged to the Delhi/CAS (38.8%) lineage, followed by Ethiopia 1 (9.7%), Ethiopia 3 (8.7%), Ethiopia H37RV-like (8.2%), Ethiopia 2 and Haarlem (7.7% each), URAL (3.6%), Uganda l and LAM (2% each), S-type (1.5%), X-type (1%), and 0.5% isolates of TUR, EAI, and Beijing genotype, respectively. Overall, 15 strains (7.7%) could not be allocated to a previously described phylogenetic lineage. The distribution of MTBC lineages is similar to that found in studies of PTB samples. The cluster rate (35%) in this study is significantly lower (P = 0.035) compared to 45% in the study of PTB in northwestern Ethiopia. CONCLUSION: In the studied area, lymph node samples are dominated by Dehli/CAS genotype strains and strains of largely not yet defined clades based on MIRU-VNTR 24-loci nomenclature. We found no indication that strains of particular genotypes are specifically associated with TBLN. However, a detailed analysis of specific genetic variants of the locally contained Ethiopian clades by whole genome sequencing may reveal new insights into the host-pathogen co-evolution and specific features that are related to the local host immune system. PMID- 26376442 TI - New and emerging roles of small RNAs in neurodegeneration, muscle, cardiovascular and inflammatory diseases. AB - Small noncoding RNAs (snRNAs) were discovered more than two decades ago, yet it was not until relatively recently that their important role in genome regulation was recognised. With such a substantial role in genome regulation, it is not surprising that snRNAs are crucial contributors to an ever-increasing number of diseases, as evidenced by the long list of published studies. Currently, microRNAs (miRNAs) represent the most intensively studied snRNAs. Dysregulation of miRNAs has been confirmed in numerous diseases, and changes in their levels could play an essential role in disease onset and progression and could be used for prognosis and potential therapy. Indeed, disease-altered miRNAs may either signify a direct trigger or a consequence of the disease. Therefore, miRNAs represent unique targets for disease intervention through their down- or up regulation. Importantly, miRNAs may facilitate disease monitoring by detection of disease-altered miRNAs in easily accessible bodily fluids, such as blood or cerebrospinal fluid. Therefore, study of these events is of utmost importance for understanding the molecular mechanisms that drive disease, as well as for diagnosis and therapy. Here we attempted to synthesise a large number of studies to highlight the crucial role of miRNAs in the pathogenesis of neurodegenerative, muscle, cardiovascular and inflammatory diseases. PMID- 26376443 TI - Citizen Science as a New Tool in Dog Cognition Research. AB - Family dogs and dog owners offer a potentially powerful way to conduct citizen science to answer questions about animal behavior that are difficult to answer with more conventional approaches. Here we evaluate the quality of the first data on dog cognition collected by citizen scientists using the Dognition.com website. We conducted analyses to understand if data generated by over 500 citizen scientists replicates internally and in comparison to previously published findings. Half of participants participated for free while the other half paid for access. The website provided each participant a temperament questionnaire and instructions on how to conduct a series of ten cognitive tests. Participation required internet access, a dog and some common household items. Participants could record their responses on any PC, tablet or smartphone from anywhere in the world and data were retained on servers. Results from citizen scientists and their dogs replicated a number of previously described phenomena from conventional lab-based research. There was little evidence that citizen scientists manipulated their results. To illustrate the potential uses of relatively large samples of citizen science data, we then used factor analysis to examine individual differences across the cognitive tasks. The data were best explained by multiple factors in support of the hypothesis that nonhumans, including dogs, can evolve multiple cognitive domains that vary independently. This analysis suggests that in the future, citizen scientists will generate useful datasets that test hypotheses and answer questions as a complement to conventional laboratory techniques used to study dog psychology. PMID- 26376444 TI - Prenatal diagnosis of left ventricular diverticulum and coarctation of the aorta. AB - Congenital left ventricular diverticulum (LVD) is a rare abnormality of the myocardium which has been detected previously in the fetus. Lesions have been reported from as early as 12 weeks' gestation but are more commonly detected in the mid-second trimester. Fetal presentation of LVD ranges from an abnormal four chamber view of the heart, arrhythmia or isolated pericardial effusion to fetal hydrops with associated heart failure. Here, we describe the prenatal diagnosis of an infant with LVD originating from the left ventricular outflow tract associated with coarctation of the aorta. The diagnosis was confirmed postnatally by two-dimensional echocardiography and cardiac magnetic resonance imaging. We hypothesize that the lesion compromised antegrade flow into the transverse aortic arch, which may have contributed to underdevelopment of the aortic arch and subsequently the development of coarctation of the aorta. This is a unique case of LVD and coarctation of the aorta. PMID- 26376445 TI - Development and evaluation of a non-peptidic ligand for the molecular imaging of inflammatory processes using S100A9 (MRP14) as a novel target. AB - The establishment of novel molecular imaging tools to monitor the local activity of inflammation remains an interdisciplinary challenge. Our target, the alarmin S100A9, one subunit of the heterodimer S100A8/S100A9 (calprotectin), is locally secreted in high concentrations from immigrated and activated phagocytes at local sites of inflammation. Calprotectin is already a well established serum biomarker for many inflammatory disorders. Here we show the development and first evaluation of the novel S100A9 specific molecular imaging probe for optical imaging of local inflammatory activity in vivo. PMID- 26376446 TI - Association of Shoulder Problems in Persons With Spinal Cord Injury at Discharge From Inpatient Rehabilitation With Activities and Participation 5 Years Later. AB - OBJECTIVE: To examine whether musculoskeletal shoulder pain and limitations in shoulder range of motion (ROM) at discharge from first rehabilitation are associated with activities and participation restrictions 5 years later in persons with spinal cord injury (SCI). DESIGN: Prospective cohort study. SETTING: Eight specialized SCI rehabilitation centers. PARTICIPANTS: Subjects (N=138) with an SCI admitted for first rehabilitation. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Peak power output (POpeak), Wheelchair Skills Test (WST), FIM motor score, ability to transfer, Physical Activity Scale for Individuals with Physical Disabilities (PASIPD), mobility range and social behavior subscales of the Sickness Impact Profile 68 (SIPSOC), and employment status. RESULTS: Mean age of the subjects at discharge was 39 years, 72% were men, 32% had tetraplegia, and in 65% the SCI was motor complete. At discharge, 39% reported shoulder pain and 32% had a limited shoulder ROM. In the analyses of variance, shoulder ROM limitation, but not shoulder pain, was associated with all but 1 outcome at 5 years. In the regression analyses, ROM limitations of the shoulder were negatively associated with the ability to transfer (P=.004), FIM motor scores (P<.001), and return to work (P= .027) 5 years after discharge. No significant associations were found with POpeak, WST performance time, SIPSOC, and PASIPD. CONCLUSIONS: The presence of limitations in shoulder ROM, but not shoulder pain, at discharge is associated with limitations in activities and employment status 5 years later. PMID- 26376447 TI - Increased Lower Limb Spasticity but Not Strength or Function Following a Single Dose Serotonin Reuptake Inhibitor in Chronic Stroke. AB - OBJECTIVE: To investigate the effects of single doses of a selective serotonin reuptake inhibitor (SSRI) on lower limb voluntary and reflex function in individuals with chronic stroke. DESIGN: Double-blind, randomized, placebo controlled crossover trial. SETTING: Outpatient research setting. PARTICIPANTS: Individuals (N=10; 7 men; mean age +/- SD, 57+/-10y) with poststroke hemiplegia of >1 year duration who completed all assessments. INTERVENTIONS: Patients were assessed before and 5 hours after single-dose, overencapsulated 10-mg doses of escitalopram (SSRI) or placebo, with 1 week between conditions. MAIN OUTCOME MEASURES: Primary assessments included maximal ankle and knee isometric strength, and velocity-dependent (30 degrees /s-120 degrees /s) plantarflexor stretch reflexes under passive conditions, and separately during and after 3 superimposed maximal volitional drive to simulate conditions of increased serotonin release. Secondary measures included clinical measures of lower limb coordination and locomotion. RESULTS: SSRI administration significantly increased stretch reflex torques at higher stretch velocities (eg, 90 degrees /s; P=.03), with reflexes at lower velocities enhanced by superimposed voluntary drive (P=.02). No significant improvements were seen in volitional peak torques or in clinical measures of lower limb function (lowest P=.10). CONCLUSIONS: Increases in spasticity but not strength or lower limb function were observed with single-dose SSRI administration in individuals with chronic stroke. Further studies should evaluate whether repeated dosing of SSRIs, or as combined with specific interventions, is required to elicit significant benefit of these agents on lower limb function poststroke. PMID- 26376448 TI - Barrierless Photoisomerization of 11-cis Retinal Protonated Schiff Base in Solution. AB - A hallmark of the primary visual event is the barrierless, ultrafast, and efficient 11-cis to all-trans photoisomerization of the retinal protonated Schiff base (RPSB) chromophore. The remarkable reactivity of RPSB in the visual pigment rhodopsin has been attributed to potential energy surface modifications enabled by evolution-optimized chromophore-protein interactions. Here, we use a combined synthetic and ultrafast spectroscopic approach to show that barrierless photoisomerization is an intrinsic property of 11-cis RPSB, suggesting that the protein may merely adjust the ratio between fast reactive and slow unreactive decay channels. These results call for a re-evaluation of our understanding and theoretical description of RPSB photochemistry. PMID- 26376449 TI - How bilingualism shapes the functional architecture of the brain: A study on executive control in early bilinguals and monolinguals. AB - The existence of a behavioral advantage of bilinguals over monolinguals during executive tasks is controversial. A new approach to this issue is to investigate the effect of bilingualism on neural control when performing these tasks as a window to understand when behavioral differences are produced. Here, we tested if early bilinguals use more language-related networks than monolinguals while performing a go/no-go task that includes infrequent no-go and go trials. The RTs and accuracy in both groups did not differ. An independent component analyses (ICA) revealed, however, that bilinguals used the left fronto-parietal network and the salience network more than monolinguals while processing go infrequent cues and no-go cues, respectively. It was noteworthy that the modulation of these networks had opposite correlates with performance in bilinguals and monolinguals, which suggests that between-group differences were more qualitative than quantitative. Our results suggest that bilinguals may differently develop the involvement of the executive control networks that comprise the left inferior frontal gyrus during cognitive control tasks than monolinguals. PMID- 26376450 TI - Missing value imputation strategies for metabolomics data. AB - The origin of missing values can be caused by different reasons and depending on these origins missing values should be considered differently and dealt with in different ways. In this research, four methods of imputation have been compared with respect to revealing their effects on the normality and variance of data, on statistical significance and on the approximation of a suitable threshold to accept missing data as truly missing. Additionally, the effects of different strategies for controlling familywise error rate or false discovery and how they work with the different strategies for missing value imputation have been evaluated. Missing values were found to affect normality and variance of data and k-means nearest neighbour imputation was the best method tested for restoring this. Bonferroni correction was the best method for maximizing true positives and minimizing false positives and it was observed that as low as 40% missing data could be truly missing. The range between 40 and 70% missing values was defined as a "gray area" and therefore a strategy has been proposed that provides a balance between the optimal imputation strategy that was k-means nearest neighbor and the best approximation of positioning real zeros. PMID- 26376451 TI - Airborne aldehydes in cabin-air of commercial aircraft: Measurement by HPLC with UV absorbance detection of 2,4-dinitrophenylhydrazones. AB - This paper presents the strategy and results of in-flight measurements of airborne aldehydes during normal operation and reported "smell events" on commercial aircraft. The aldehyde-measurement is a part of a large-scale study on cabin-air quality. The aims of this study were to describe cabin-air quality in general and to detect chemical abnormalities during the so-called "smell-events". Adsorption and derivatization of airborne aldehydes on 2,4-dinitrophenylhydrazine coated silica gel (DNPH-cartridge) was applied using tailor-made sampling kits. Samples were collected with battery supplied personal air sampling pumps during different flight phases. Furthermore, the influence of ozone was investigated by simultaneous sampling with and without ozone absorption unit (ozone converter) assembled to the DNPH-cartridges and found to be negligible. The method was validated for 14 aldehydes and found to be precise (RSD, 5.5-10.6%) and accurate (recovery, 98-103 %), with LOD levels being 0.3-0.6 MUg/m(3). According to occupational exposure limits (OEL) or indoor air guidelines no unusual or noticeable aldehyde pollution was observed. In total, 353 aldehyde samples were taken from two types of aircraft. Formaldehyde (overall average 5.7 MUg/m(3), overall median 4.9 MUg/m(3), range 0.4-44 MUg/m(3)), acetaldehyde (overall average 6.5 MUg/m(3), overall median 4.6, range 0.3-90 MUg/m(3)) and mostly very low concentrations of other aldehydes were measured on 108 flights. Simultaneous adsorption and derivatization of airborne aldehydes on DNPH-cartridges to the Schiff bases and their HPLC analysis with UV absorbance detection is a useful method to measure aldehydes in cabin-air of commercial aircraft. PMID- 26376453 TI - Rhinos in the Parks: An Island-Wide Survey of the Last Wild Population of the Sumatran Rhinoceros. AB - In the 200 years since the Sumatran rhinoceros was first scientifically described (Fisher 1814), the range of the species has contracted from a broad region in Southeast Asia to three areas on the island of Sumatra and one in Kalimantan, Indonesia. Assessing population and spatial distribution of this very rare species is challenging because of their elusiveness and very low population number. Using an occupancy model with spatial dependency, we assessed the fraction of the total landscape occupied by Sumatran rhinos over a 30,345-km2 survey area and the effects of covariates in the areas where they are known to occur. In the Leuser Landscape (surveyed in 2007), the model averaging result of conditional occupancy estimate was psi(SE[psi]) = 0.151(0.109) or 2,371.47 km2, and the model averaging result of replicated level detection probability p(SE[p]) = 0.252(0.267); in Way Kambas National Park--2008: psi(SE[psi]) = 0.468(0.165) or 634.18 km2, and p(SE[p]) = 0.138(0.571); and in Bukit Barisan Selatan National Park--2010: psi(SE[psi]) = 0.322(0.049) or 819.67 km2, and p(SE[p]) = 0.365(0.42). In the Leuser Landscape, rhino occurrence was positively associated with primary dry land forest and rivers, and negatively associated with the presence of a road. In Way Kambas, occurrence was negatively associated with the presence of a road. In Bukit Barisan Selatan, occurrence was negatively associated with presence of primary dryland forest and rivers. Using the probabilities of site occupancy, we developed spatially explicit maps that can be used to outline intensive protection zones for in-situ conservation efforts, and provide a detailed assessment of conserving Sumatran rhinos in the wild. We summarize our core recommendation in four points: consolidate small population, strong protection, determine the percentage of breeding females, and recognize the cost of doing nothing. To reduce the probability of poaching, here we present only the randomized location of site level occupancy in our result while retaining the overall estimation of occupancy for a given area. psi PMID- 26376454 TI - Physiological and molecular mechanisms associated with cross tolerance between hypoxia and low temperature in Thaumatotibia leucotreta. AB - Biochemical adaptations allow insects to withstand exposures to hypoxia and/or hypothermia. Exposure to hypoxia may interact either synergistically or antagonistically with standard low temperature stress responses yet this has not been systematically researched and no clear mechanism has been identified to date. Using larvae of false codling moth Thaumatotibia leucotreta, a pest of southern Africa, we investigated the physiological and molecular responses to hypoxia or temperature stress pre-treatments, followed by a standard low temperature exposure. Survival rates were significantly influenced by pre treatment conditions, although T. leucotreta shows relatively high basal resistance to various stressors (4% variation in larval survival across all pre treatments). Results showed that mild pre-treatments with chilling and hypoxia increased resistance to low temperatures and that these responses were correlated with increased membrane fluidity (increased UFA:SFA) and/or alterations in heat shock protein 70 (HSP70); while general mechanical stress (shaking) and heat (2h at 35 degrees C) do not elicit cross tolerance (no change in survival or molecular responses). We therefore found support for some limited cold hardening and cross tolerance responses. Given that combined exposure to hypoxia and low temperature is used to sterilize commodities in post-harvest pest management programs, researchers can now exploit these mechanisms involved in cross tolerance to develop more targeted control methods. PMID- 26376452 TI - Micronutrients Involved in One-Carbon Metabolism and Risk of Breast Cancer Subtypes. AB - BACKGROUND: Vitamins involved in one-carbon metabolism are hypothesized to influence breast cancer (BC) risk. However, epidemiologic studies that examined associations between B vitamin intake and BC risk have provided inconsistent results. We prospectively examined, in the Italian ORDET cohort, whether B vitamin consumption was associated with risk of BC and BC subtypes. METHODS: After a mean follow-up of 16.5 years, 391 BCs were diagnosed among 10,786 cohort women. B vitamin intakes were estimated from food frequency questionnaires. Cox proportional hazard models adjusted for energy intake and confounders, estimated hazard ratios (HR) with 95% confidence intervals (CIs) for BC according to intake. RESULTS: RRs were 0.61 (95% CI 0.38-0.97 highest vs. lowest quartile; P trend 0.025) for thiamine; 0.48 (95% CI 0.32-0.71; P trend <0.001) for riboflavin; 0.59 (95% CI 0.39-0.90; P trend 0.008) for vitamin B6, and 0.65 (95% CI 0.44-0.95; P trend 0.021) for folate. As regards risk of BC subtypes, high riboflavin and folate were significantly associated with lower risk of estrogen receptor positive (ER+) and progesterone receptor positive (PR+) cancers, and high thiamine was associated with lower risk of ER-PR- cancers. High riboflavin was associated with lower risk of both HER2+ and HER2- cancers, high folate with lower risk of HER2- disease, and high thiamine with HER2+ disease. CONCLUSIONS: These findings support protective effects of thiamine and one-carbon metabolism vitamins (folate, riboflavin, and vitamin B6) against BC in general; while folate may also protect against ER+PR+ and HER2- disease; and thiamine against ER-PR-, and HER2+ disease. PMID- 26376455 TI - Cdk5 at crossroads of protein oligomerization in neurodegenerative diseases: facts and hypotheses. AB - Cyclin-dependent kinase 5 (Cdk5) is involved in proper neurodevelopment and brain function and serves as a switch between neuronal survival and death. Overactivation of Cdk5 is associated with many neurodegenerative disorders such as Alzheimer's or Parkinson's diseases. It is believed that in those diseases Cdk5 may be an important link between disease-initiating factors and cell death effectors. A common hallmark of neurodegenerative disorders is incorrect folding of specific proteins, thus leading to their intra- and extracellular accumulation in the nervous system. Abnormal Cdk5 signaling contributes to dysfunction of individual proteins and has a substantial role in either direct or indirect interactions of proteins common to, and critical in, different neurodegenerative diseases. While the roles of Cdk5 in alpha-synuclein (ASN) - tau or beta-amyloid peptide (Abeta) - tau interactions are well documented, its contribution to many other pertinent interactions, such as that of ASN with Abeta, or interactions of the Abeta - ASN - tau triad with prion proteins, did not get beyond plausible hypotheses and remains to be proven. Understanding of the exact position of Cdk5 in the deleterious feed-forward loop critical for development and progression of neurodegenerative diseases may help designing successful therapeutic strategies of several fatal neurodegenerative diseases. Cyclin-dependent kinase 5 (Cdk5) is associated with many neurodegenerative disorders such as Alzheimer's or Parkinson's diseases. It is believed that in those diseases Cdk5 may be an important factor involved in protein misfolding, toxicity and interaction. We suggest that Cdk5 may contribute to the vicious circle of neurotoxic events involved in the pathogenesis of different neurodegenerative diseases. PMID- 26376457 TI - Can Walmart make us healthier? Prescription drug prices and health care utilization. AB - This paper analyzes how prices in the retail pharmaceutical market affect health care utilization. Specifically, I study the impact of Walmart's $4 Prescription Drug Program on utilization of antihypertensive drugs and on hospitalizations for conditions amenable to drug therapy. Identification relies on the change in the availability of cheap drugs introduced by Walmart's program, exploiting variation in the distance to the nearest Walmart across ZIP codes in a difference-in differences framework. I find that living close to a source of cheap drugs increases utilization of antihypertensive medications by 7 percent and decreases the probability of an avoidable hospitalization by 6.2 percent. PMID- 26376458 TI - Electroencephalogram of Healthy Horses During Inhaled Anesthesia. AB - BACKGROUND: Previous study of the diagnostic validity of electroencephalography (EEG) to detect abnormalities in equine cerebral cortical function relied on the administration of various drugs for sedation, induction, and maintenance of general anesthesia but used identical criteria to interpret recordings. OBJECTIVES: To determine the effects of 2 inhalation anesthetics on the EEG of healthy horses. ANIMALS: Six healthy horses. METHODS: Prospective study. After the sole administration of one of either isoflurane or halothane at 1.2, 1.4, and 1.6 times the minimum alveolar concentration, EEG was recorded during controlled ventilation, spontaneous ventilation, and nerve stimulation. RESULTS: Burst suppression was observed with isoflurane, along with EEG events that resembled epileptiform discharges. Halothane results were variable between horses, with epileptiform-like discharges and bursts of theta, alpha, and beta recorded intermittently. One horse died and 2 were euthanized as the result of anesthesia related complications. CONCLUSIONS AND CLINICAL IMPORTANCE: The results of this study indicate that the effects of halothane and isoflurane on EEG activity in the normal horse can be quite variable, even when used in the absence of other drugs. It is recommended that equine EEG be performed without the use of these inhalation anesthetics and that general anesthesia be induced and maintained by other contemporary means. PMID- 26376460 TI - How different terminology for ductal carcinoma in situ (DCIS) impacts women's concern and management preferences: A qualitative study. AB - OBJECTIVE: There are increasing rates of mastectomy and bi-lateral mastectomy in women diagnosed with ductal carcinoma in situ (DCIS). To help women avoid decisions that lead to unnecessary aggressive treatments, there have been recent calls to remove the cancer terminology from descriptions of DCIS. We investigated how different proposed terminologies for DCIS affect women's perceived concern and management preferences. MATERIALS AND METHODS: Qualitative study using semi structured interviews with a community sample of 26 Australian women varying by education and cancer screening experience. Women responded to a hypothetical scenario using terminology with and without the cancer term to describe DCIS. RESULTS: Among a sample of women with no experience of a DCIS diagnosis, a hypothetical scenario involving a diagnosis of DCIS elicited high concern regardless of the terminology used to describe it. Women generally exhibited stronger negative reactions when a cancer term was used to describe DCIS compared to a non-cancer term, and most preferred the diagnosis be given as a description of abnormal cells. Overall women expressed interest in watchful waiting for DCIS but displayed preferences for very frequent monitoring with this management approach. CONCLUSION: Communicating a diagnosis of DCIS using terminology that does not include the cancer term was preferred by many women and may enable discussions about more conservative management options. However, women's preference for frequent monitoring during watchful waiting suggests women need more education and reassurance about this management approach. PMID- 26376461 TI - Meta-analysis of randomized controlled trials for the incidence and risk of treatment-related mortality in patients with breast cancer treated with HER2 blockade. AB - PURPOSE: The association between human epidermal growth factor receptor-2 (HER2) blockades and risk of fatal adverse events (FAEs) has not been well described. We carried out a meta-analysis regarding this issue. METHODS: An electronic search of Medline, Embase and The Cochrane Central Register of Controlled Trials was conducted to investigate the effects of anti-HER2 therapies on cancer patients. Only randomized controlled trials were included. Random or fixed-effect meta analytical models were used to evaluate the risk ratio (RR) of FAEs due to the use of HER2 blockades. RESULTS: Twenty two trials were included. The incidence of FAEs related to HER2 blockades was 0.34%, and there was no statistically significant increase in the risk of FAEs for HER2 blockades versus control in overall population (RR = 1.16, 95%CI: 0.78-1.73). Furthermore, when we performed several subgroup analyses according to drug type (trastuzumab, lapatinib, and pertuzumab), treatment strategy (dual HER2 blockade vs. mono HER2 therapy), and study setting (adjuvant trials vs. metastatic trials), we did not observe any significant differences among the groups. No evidence of publication bias was observed. CONCLUSION: Compared with control, the addition of HER2 blockades may not increase the risk of FAEs among patients with breast cancer. PMID- 26376459 TI - Activity and Toxicity of Intravenous Erwinia Asparaginase Following Allergy to E. coli-Derived Asparaginase in Children and Adolescents With Acute Lymphoblastic Leukemia. AB - BACKGROUND: Erwinia asparaginase is antigenically distinct from E.coli-derived asparaginase and may be used after E.coli-derived asparaginase hypersensitivity. In a single-arm, multicenter study, we evaluated nadir serum asparaginase activity (NSAA) and toxicity with intravenously administered asparaginase Erwinia chrysanthemi (IV-Erwinia) in children and adolescents with acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma with hypersensitivity to E.coli-derived asparaginase. PATIENTS AND METHODS: Between 2012 and 2013, 30 patients (age 1-17 years) enrolled from 10 centers. Patients received IV-Erwinia, 25,000 IU/m(2)/dose on Monday/Wednesday/Friday, for 2 consecutive-weeks (6 doses = 1 cycle) for each dose of pegaspargase remaining in the original treatment plan. The primary objective was to determine the proportion of patients achieving NSAA >= 0.1 IU/ml 48 hr after dose 5 in Cycle 1. Secondary objectives included determining the proportion achieving NSAA >= 0.1 IU/ml 72 hr after Cycle 1 dose 6, and the frequency of asparaginase-related toxicities. RESULTS: Twenty-six patients completed Cycle 1; 24 were evaluable for NSAA assessment. In Cycle 1, NSAA >= 0.10 IU/ml was detected in 83% of patients (95% confidence interval [CI], 63-95%) 48 hr post-dose 5 (mean +/- SD; 0.32 IU/ml +/- 0.23), and in 43% (95% CI, 22-66%) 72 hr post-dose 6 (mean +/- SD; 0.089 IU/ml +/- 0.072). For all 30 patients over all cycles, hypersensitivity/infusional reactions with IV-Erwinia occurred in 37%, pancreatitis 7%, and thrombosis 3%. CONCLUSIONS: IV-Erwinia administration in children/adolescents appeared feasible and tolerable. A therapeutically-effective NSAA (>= 0.10 IU/ml) was achieved in most patients at 48 hr, but in fewer than half 72 hr post-dosing, suggesting that monitoring NSAA levels and/or every 48 hr dosing may be indicated. PMID- 26376462 TI - Textual inference for eligibility criteria resolution in clinical trials. AB - Clinical trials are essential for determining whether new interventions are effective. In order to determine the eligibility of patients to enroll into these trials, clinical trial coordinators often perform a manual review of clinical notes in the electronic health record of patients. This is a very time-consuming and exhausting task. Efforts in this process can be expedited if these coordinators are directed toward specific parts of the text that are relevant for eligibility determination. In this study, we describe the creation of a dataset that can be used to evaluate automated methods capable of identifying sentences in a note that are relevant for screening a patient's eligibility in clinical trials. Using this dataset, we also present results for four simple methods in natural language processing that can be used to automate this task. We found that this is a challenging task (maximum F-score=26.25), but it is a promising direction for further research. PMID- 26376463 TI - High-school seniors' college enrollment goals: Costs and benefits of ambitious expectations. AB - High school students with high long-term educational expectations attain higher levels of education than those with lower expectations. Less studied is the role of students' short-term college enrollment expectations for the year after high school graduation. The purpose of the current study was to examine the costs and benefits of ambitious short-term expectations and the impact of falling short of these expectations on mental health, motivation, and educational outcomes. Over 1000 youth with expectations to attend college were surveyed during their senior year of high school, one year later, and four years later. Participants who did not achieve their short-term expectations had lower educational attainment four years later but were not less satisfied with their educational progress. The negative consequences of falling short of one's expectations were restricted to individuals with less ambitious short-term expectations. Thus, the benefits of ambitious short-term expectations for youth may outweigh the costs. PMID- 26376464 TI - Liraglutide treatment causes upregulation of adiponectin and downregulation of resistin in Chinese type 2 diabetes. AB - AIMS: To assess the effect of 16 weeks of liraglutide administration on the plasma levels of adiponectin and resistin in Chinese patients diagnosed with type 2 diabetes mellitus (T2DM). METHODS: Forty-four subjects were recruited and randomly assigned to once-a-day dosage of either liraglutide, or glimepiride (4 mg) in a double-blinded double-dummy active-controlled study. All treatments were administered in combination with metformin (1 g, twice daily). The efficacy of liraglutide was estimated by measuring and comparing the levels of HbA1c, adiponectin and resistin in the plasma before and after the 16-week treatment. RESULTS: The plasma level of adiponectin was significantly increased (0.74+/-0.19 ng/ml, p<0.05) and resistin was significantly lowered (-1.34+/-0.34 pg/ml, p<0.05) in a dose-dependent manner in the liraglutide group when compared with the glimepiride group (-0.44+/-0.09 ng/ml of adiponectin and 0.14+/-0.41 pg/ml of resistin). In contrast, we found no differences in the decrease in HbA1c between the two groups (8.3+/-1.2% to 7.2+/-1.1% in NGSP units vs. 8.3+/-1.0% to 7.3+/ 1.2% in NGSP units; 67+/-13 mmol/mol to 55+/-12 mmol/mol vs. 67+/-11 mmol/mol to 56+/-13 mmol/mol in IFCC units). CONCLUSIONS: In Chinese T2DM patients, liraglutide treatment led to increased adiponectin and decreased resistin levels compared to glimepiride-treated subjects, while inducing similar glycemic changes. PMID- 26376465 TI - Volumetric tracking of migratory melanophores during zebrafish development by optoacoustic microscopy. AB - Unveiling mechanisms driving specification, recruitment and regeneration of melanophores is key in understanding melanin-related disorders. This study reports on the applicability of a hybrid focus optoacoustic microscope (HFOAM) for volumetric tracking of migratory melanophores in developing zebrafish. The excellent contrast from highly-absorbing melanin provided by the method is shown to be ideal for label-free dynamic visualization of melanophores in their unperturbed environment. We established safe laser energy levels that enable high contrast longitudinal tracking of the cells over an extended period of developmental time without causing cell toxicity or pigment bleaching. Owing to its hybrid optical and acoustic resolution, the new imaging technique can be seamlessly applied for noninvasive studies of both optically-transparent larval as well as adult stages of the zebrafish model organism, which is not possible using other optical microscopy methods. PMID- 26376466 TI - Epithelioid pleural mesothelioma concurrently associated with miliary pulmonary metastases and minimal change nephrotic syndrome - A hitherto undescribed case. AB - Malignant pleural mesothelioma (MPM) is the aggressive disease typically spreading along the pleural surface and encasing the lung, leading to respiratory failure or cachexia. Rare cases with atypical clinical manifestation or presentation have been reported in MPM. We experienced a unique case of MPM concurrently associated with miliary pulmonary metastases and nephrotic syndrome. A 73-year-old Japanese man with past history of asbestos exposure was referred to our hospital for the investigation of the left pleural effusion. Chest computed tomography showed thickening of the left parietal pleura. Biopsy specimen of the pleura showed proliferating epithelioid tumor cells, leading to the pathological diagnosis of epithelioid MPM with the aid of immunohistochemistry. After the diagnosis of MPM, chemotherapy was performed without effect. Soon after the clinical diagnosis of progressive disease with skull metastasis, edema and weight gain appeared. Laboratory data met the criteria of nephrotic syndrome, and renal biopsy with electron microscopic examination revealed the minimal change disease. Steroid therapy was started but showed no effect. Around the same time of onset of nephrotic syndrome, multiple miliary lung nodules appeared on chest CT. Transbronchial biopsy specimen of the nodules showed the metastatic MPM in the lung. The patient died because of the worsening of the general condition. To our knowledge, this is the first case of MPM concurrently associated with multiple miliary pulmonary metastases and nephrotic syndrome. PMID- 26376467 TI - Expression of proinflammatory cytokine interleukin-6 in tissue samples of human prostate obtained by needle biopsy. AB - Interleukin-6 (IL-6) has been associated with the development of prostate cancer. The aim of the study was to clarify whether IL-6 expression in prostate tissue could be a useful marker in differentiation of prostate diseases in small foci by pathologist visual scoring. Archival paraffin-embedded specimens of benign prostate hyperplasia (BPH), high-grade prostatic intraepithelial neoplasia (PIN), prostatitis and prostate adenocarcinoma were studied by immunohistochemistry with a mouse monoclonal antibody IL-6 using the streptavidin-biotin method. Significantly, lower IL-6 immunoreactivity was observed in normal epithelial cells (p=0.000) and basal cells (p=0.000) in the samples of prostate adenocarcinoma in comparison to the samples with BPH, PIN and prostatitis. There was no significant difference in IL-6 expression in malignant and premalignant cells (p=0.814) as well as in stromal cells among the four diagnoses (p=0.22). IL 6 was expressed in normal epithelial cells, premalignant epithelial cells and malignant epithelial cells as well as in stromal cells. However, in our research IL-6 was of limited utility as a single marker for differential diagnosis of the prostate diseases in small foci needle biopsy by pathologist visual scoring. The standardization of immunohistochemical (IHC) staining protocol for IL-6 is required to determine IL-6 expression in order to avoid possible misinterpretation of the IHC results. PMID- 26376468 TI - The complete genome sequence of a high pristinamycin-producing strain Streptomyces pristinaespiralis HCCB10218. AB - Streptomyces pristinaespiralis produces the streptogramin-like antibiotic pristinamycin, which is a mixture of two structurally different components: pristinamycin I (PI) and pristinamycin II (PII). Herein, we report the complete genome sequence of a high pristinamycin-producing strain HCCB10218 (8.5 Mb) obtained by using PacBio RSII combined with Illumina HiSeq 2500 sequencing system. The genome sequence presented here provides clues for the mechanism underlying the higher pristinamycin production of HCCB10218. PMID- 26376469 TI - Sporosarcina pasteurii use in extreme alkaline conditions for recycling solid industrial wastes. AB - The ureolytic bacteria are one of the most efficient organisms able to produce high amounts of carbonate that easily react with the free calcium ions from the environment. Sporosarcina pasteurii, a robust microbe in alkaline environments, was tested in this work for its potential use in an eco-cementation process that involves the biomediated calcite precipitation (BCP). Bacterial behavior in extreme alkaline environment (pH values of 9-13) was tested in controlled laboratory conditions and in the presence of solid industry wastes, such as Cement Kiln Dust (CKD) and Lime Kiln Dust (LKD), by evaluating the enzymatic activity and the calcite precipitation capacity. Grain consolidation potential of S. pasteurii was tested for one type of CKD mixed with ground granulated blast furnace slag (GGBS), with possible bioclogging and biocementation applications. The results revealed the formation of stable biocalcite in the presence of CKD, with a performance depending on the pH-value and free calcium ion content. The BCP induced by S. pasteurii and the recycling of solid wastes, such as CKD with high lime content, is a promising way for different bioclogging and biocementation applications, with benefits in construction costs and reduction of environmental pollution. PMID- 26376470 TI - Complete genome sequence of Streptomyces sp. strain CFMR 7, a natural rubber degrading actinomycete isolated from Penang, Malaysia. AB - Streptomyces sp. strain CFMR 7, which naturally degrades rubber, was isolated from a rubber plantation. Whole genome sequencing and assembly resulted in 2 contigs with total genome size of 8.248 Mb. Two latex clearing protein (lcp) genes which are responsible for rubber degrading activities were identified. PMID- 26376471 TI - Complete genome sequence of Serratia fonticola DSM 4576 T, a potential plant growth promoting bacterium. AB - Here, we present the first complete genome sequence of Serratia fonticola DSM 4576(T), a potential plant growth promoting (PGP) bacterium which confers solubilization of inorganic phosphate, indole-3-acetic acid production, hydrogen cyanideproduction, siderophore production and assimilation of ammonia through the glutamate synthase (GS/GOGAT) pathway. This genome sequence is valuable for functional genomics and ecological studies which are related to PGP and biocontrol activities. PMID- 26376472 TI - Complete genome sequence of Lactobacillus acetotolerans RIB 9124 (NBRC 13120) isolated from putrefied (hiochi) Japanese sake. AB - Lactobacillus acetotolerans RIB 9124 (NBRC 13120) was isolated from putrefied (hiochi) Japanese sake. Here we report the complete genome sequence of this organism. This paper is the first report demonstrating the fully sequenced and completely annotated genome of a L. acetotolerans strain. PMID- 26376473 TI - GIPSy: Genomic island prediction software. AB - Bacteria are highly diverse organisms that are able to adapt to a broad range of environments and hosts due to their high genomic plasticity. Horizontal gene transfer plays a pivotal role in this genome plasticity and in evolution by leaps through the incorporation of large blocks of genome sequences, ordinarily known as genomic islands (GEIs). GEIs may harbor genes encoding virulence, metabolism, antibiotic resistance and symbiosis-related functions, namely pathogenicity islands (PAIs), metabolic islands (MIs), resistance islands (RIs) and symbiotic islands (SIs). Although many software for the prediction of GEIs exist, they only focus on PAI prediction and present other limitations, such as complicated installation and inconvenient user interfaces. Here, we present GIPSy, the genomic island prediction software, a standalone and user-friendly software for the prediction of GEIs, built on our previously developed pathogenicity island prediction software (PIPS). We also present four application cases in which we crosslink data from literature to PAIs, MIs, RIs and SIs predicted by GIPSy. Briefly, GIPSy correctly predicted the following previously described GEIs: 13 PAIs larger than 30kb in Escherichia coli CFT073; 1 MI for Burkholderia pseudomallei K96243, which seems to be a miscellaneous island; 1 RI of Acinetobacter baumannii AYE, named AbaR1; and, 1 SI of Mesorhizobium loti MAFF303099 presenting a mosaic structure. GIPSy is the first life-style-specific genomic island prediction software to perform analyses of PAIs, MIs, RIs and SIs, opening a door for a better understanding of bacterial genome plasticity and the adaptation to new traits. PMID- 26376474 TI - Rolling resistance and propulsion efficiency of manual and power-assisted wheelchairs. AB - Rolling resistance is one of the main forces resisting wheelchair propulsion and thus affecting stress exerted on the upper limbs. The present study investigates the differences in rolling resistance, propulsion efficiency and energy expenditure required by the user during power-assisted and manual propulsion. Different tire pressures (50%, 75%, 100%) and two different levels of motor assistance were tested. Drag force, energy expenditure and propulsion efficiency were measured in 10 able-bodied individuals under different experimental settings on a treadmill. Results showed that drag force levels were significantly higher in the 50%, compared to the 75% and 100% inflation conditions. In terms of wheelchair type, the manual wheelchair displayed significantly lower drag force values than the power-assisted one. The use of extra-power-assisted wheelchair appeared to be significantly superior to conventional power-assisted and manual wheelchairs concerning both propulsion efficiency and energy expenditure required by the user. Overall, the results of the study suggest that the use of power assisted wheelchair was more efficient and required less energy input by the user, depending on the motor assistance provided. PMID- 26376475 TI - Portal hypertensive gastropathy and gastric antral vascular ectasia. AB - PURPOSE OF REVIEW: Portal hypertensive gastropathy (PHG) and gastric antral vascular ectasia (GAVE) are two types of upper gastrointestinal bleeding that may present similarly, but are managed very differently. This article reviews the pathogenesis and guidelines in management of both of these conditions with emphasis on recent advances in the field. RECENT FINDINGS: Off-label use of Hemospray has been shown in several case series to be useful in managing acute bleeding from PHG. Balloon-occluded retrograde transvenous obliteration presents an alternative approach for this condition. Radiofrequency ablation may be an alternative therapy to argon plasma coagulation in the endoscopic treatment of GAVE, as it consists of fewer sessions and has been shown to decrease gastrointestinal blood loss. SUMMARY: The treatment options for PHG and GAVE are constantly evolving and expanding. In this review, we present the latest approaches in the gastroenterologist's arsenal to deal with these conditions. PMID- 26376477 TI - Functional anatomy and physiology of gastric secretion. AB - PURPOSE OF REVIEW: This review summarizes the past year's literature regarding the neuroendocrine and intracellular regulation of gastric acid secretion, discussing both basic and clinical aspects. RECENT FINDINGS: Gastric acid facilitates the digestion of protein as well as the absorption of iron, calcium, vitamin B12, and certain medications. High acidity kills ingested microorganisms and limits bacterial overgrowth, enteric infection, and possibly spontaneous bacterial peritonitis. The main stimulants of acid secretion are gastrin, released from antral gastrin cells; histamine, released from oxyntic enterochromaffin-like cells; and acetylcholine, released from antral and oxyntic intramural neurons. Ghrelin and coffee also stimulate acid secretion whereas somatostatin, cholecystokinin, glucagon-like peptide-1, and atrial natriuretic peptide inhibit acid secretion. Although 95% of parietal cells are contained within the oxyntic mucosa (fundus and body), 50% of human antral glands contain parietal cells. Proton pump inhibitors are considered well tolerated drugs, but concerns have been raised regarding dysbiosis, atrophic gastritis, hypergastrinemia, hypomagnesemia, and enteritis/colitis. SUMMARY: Our understanding of the functional anatomy and physiology of gastric secretion continues to advance. Such knowledge is crucial for improved management of acid peptic disorders, prevention and management of neoplasia, and the development of novel medications. PMID- 26376476 TI - Gastroduodenal mucosal defense mechanisms. AB - PURPOSE OF REVIEW: To highlight recent developments in the field of gastroduodenal mucosal defense with emphasis on lumen-gut interactions. RECENT FINDINGS: There has been a growing interest in the physiological functions of luminal chemosensors present from tongue to colon that detect organic molecules in the luminal content associated with nutrient ingestion, usually associated with specialized cells, in particular the enteroendocrine cells. These receptors transduce the release of peptide hormones, in particular proglucagon-derived products such as the glucagon-like peptides (GLPs), which have profound effects on gut function and on metabolism. Luminal chemosensors transduce GLP release in response to changes in the cellular environment, as part of the mechanism of nutrient chemosensing. GLP-2 has important trophic effects on the intestinal mucosa, including increasing the proliferation rate of stem cells and reducing transmucosal permeability to ions and small molecules, in addition to increasing the rate of duodenal bicarbonate secretion. GLP-1, although traditionally considered an incretin that enhances the effect of insulin on peripheral tissues, also has trophic effects on the intestinal epithelium. SUMMARY: A better understanding of the mechanisms that mediate GLP release can further illuminate the importance of nutrient chemosensing as an important component of the mechanism that mediates the trophic effects of luminal nutrients. GLP-1 and GLP-2 are already in clinical use for the treatment of diabetes and intestinal failure. Improved understanding of the control of their release and their end-organ effects will identify new clinical indications and interventions that enhance their release. PMID- 26376478 TI - Role of type 2 immunity in intestinal inflammation. AB - PURPOSE OF REVIEW: Type 2 (Th2) immune responses play important roles in intestinal immunity by contributing to the maintenance of mucosal homeostasis, not only conferring protection against helminthic infection but also participating in pro-inflammatory pathways in chronic intestinal inflammatory disorders, including inflammatory bowel disease. The current review focuses on recent developments regarding the role of Th2 responses in intestinal inflammation. RECENT FINDINGS: Th2 gut mucosal responses are promoted by mediators that are released following injury to the epithelium, and act as alarmin-type danger signals. Interleukin (IL)-33 is prominent among such factors and demonstrates a dichotomous function, exerting either protective or pro inflammatory effects, depending on its cellular compartmentalization. The pool of type 2 effector cells has been enriched recently to include not only classical CD4+ Th2 lymphocytes but also a subset of innate lymphocytes (ILC2s) that express the transcriptional factor GATA binding protein 3 and secrete IL-4, IL-5, and IL 13. ILC2s play important roles during infection with helminths and bi directionally interact with Th2 CD4+ lymphocytes, thus establishing a transition from innate to adaptive immunological pathways. Th2 responses are also involved in pro-inflammatory pathways at the intestinal mucosa, and neutralization of the pivotal cytokines IL-4 and IL-13 has been shown to regulate experimental intestinal inflammation. In striking contrast, however, neutralization of human IL-13 had no therapeutic effect in patients with ulcerative colitis. SUMMARY: Further studies will be required to delineate the specific mechanisms of type 2 mucosal immunity in inflammatory bowel disease and examine the applicability of Th2-targeted therapies for intestinal inflammation. PMID- 26376479 TI - RbAp48 Is Critical for the Proliferation of Hypopharyngeal Carcinoma. AB - BACKGROUND: Emerging evidence has indicated the significance of RbAp48 in tumorigenesis. Although many genetic and epigenetic factors have been found to be involved in the pathogenesis of hypopharyngeal carcinoma, the effect of RbAp48 in hypopharyngeal carcinoma is still unclear. METHODS: A stable cell line overexpressing RbAp48 was generated in FaDu cells. Cell proliferation and colony formation were detected using FaDu-RbAp48 cells. Next we utilized nude mouse xenografts to determine the role of RbAp48. Flow cytometry was employed to investigate the effect of RbAp48 in cell cycle distribution and apoptosis. Real time PCR was used to detect the expression of tumor suppressors and apoptosis related factors. RESULTS: The overexpression of RbAp48 inhibited cell proliferation, colony formation, and tumor formation in nude mice. The overexpression of RbAp48 affected cell cycle distribution and induced apoptosis. The expression of p53, Rb, Bax, caspase 3, caspase 8, and caspase 9 was upregulated, whereas the expression of Bcl-2 was downregulated resulting from the overexpression of RbAp48. CONCLUSION: RbAp48 was identified as critical in the proliferation of hypopharyngeal carcinoma in both in vitro and in vivo experiments. It is conceivable that the regulation of tumor suppressors (Bcl-2 family and caspase enzymes) by RbAp48 contributes, at least in part, to the RbAp48-mediated proliferation in hypopharyngeal carcinoma. PMID- 26376480 TI - The Potential Regulatory Mechanisms of miR-196a in Huntington's Disease through Bioinformatic Analyses. AB - High throughput screening is a powerful tool to identify the potential candidate molecules involved during disease progression. However, analysis of complicated data is one of the most challenging steps on the way to obtaining useful results from this approach. Previously, we showed that a specific miRNA, miR-196a, could ameliorate the pathological phenotypes of Huntington's disease (HD) in different models, and performed high throughput screening by using the striatum of transgenic mice. In this study, we further tried to identify the potential regulatory mechanisms using different bioinformatic tools, including Database for Annotation, Visualization and Integrated Discovery (DAVID), Molecular Signatures Database (MSigDB), TargetScan and MetaCore. The results showed that miR-196a dominantly altered "ABC transporters", "RIG-I-like receptor signaling pathway", immune system", "adaptive immune system","tissue remodeling and wound repair" and "cytoskeleton remodeling". In addition, miR-196a also changed the expression of several well-defined pathways of HD, such as apoptosis and cell adhesion. Since these analyses showed the regulatory pathways are highly related to the modification of the cytoskeleton, we further confirmed that miR-196a could enhance the neurite outgrowth in neuroblastoma cells, suggesting miR-196a might provide beneficial functions through the alteration of cytoskeleton structures. Since impairment of the cytoskeleton has been reported in several neuronal diseases, this study will provide not only the potential working mechanisms of miR-196a but also insights for therapeutic strategies for use with different neuronal diseases. PMID- 26376482 TI - Police investigations: discretion denied yet undeniably exercised. AB - Police investigations involve determining whether a crime has been committed, and if so what type of crime, who has committed it and whether there is the evidence to charge the perpetrators. Drawing on fieldwork in Delhi and Mumbai, this paper explores how police investigations unfolded in the specific context of women's deaths by burning in India. In particular, it focuses on the use of discretion despite its denial by those exercising it. In India, there are distinctive statutes relating to women's suspicious deaths, reflecting the widespread expectation that the bride's family will pay a dowry to the groom's family and the tensions to which this may on occasion give rise in the early years of a marriage. Often, there are conflicting claims influencing how the woman's death is classified. These in turn affect police investigation. The nature and direction of police discretion in investigating women's deaths by burning reflect in part the unique nature of the legislation and the particular sensitivities in relation to these types of death. They also highlight processes that are liable to be at work in any crime investigation. It was found that police officers exercised unacknowledged discretion at seven specific points in the investigative process, with potentially significant consequences for the achievement of just outcomes: first response, recording the victim's 'dying declaration', inquest, registering of the 'First Information Report', collecting evidence, arrest and framing of the charges. PMID- 26376481 TI - Ketocarotenoid Production in Soybean Seeds through Metabolic Engineering. AB - The pink or red ketocarotenoids, canthaxanthin and astaxanthin, are used as feed additives in the poultry and aquaculture industries as a source of egg yolk and flesh pigmentation, as farmed animals do not have access to the carotenoid sources of their wild counterparts. Because soybean is already an important component in animal feed, production of these carotenoids in soybean could be a cost-effective means of delivery. In order to characterize the ability of soybean seed to produce carotenoids, soybean cv. Jack was transformed with the crtB gene from Pantoea ananatis, which codes for phytoene synthase, an enzyme which catalyzes the first committed step in the carotenoid pathway. The crtB gene was engineered together in combinations with ketolase genes (crtW from Brevundimonas sp. strain SD212 and bkt1 from Haematococcus pluvialis) to produce ketocarotenoids; all genes were placed under the control of seed-specific promoters. HPLC results showed that canthaxanthin is present in the transgenic seeds at levels up to 52 MUg/g dry weight. Transgenic seeds also accumulated other compounds in the carotenoid pathway, such as astaxanthin, lutein, beta carotene, phytoene, alpha-carotene, lycopene, and beta-cryptoxanthin, whereas lutein was the only one of these detected in non-transgenic seeds. The accumulation of astaxanthin, which requires a beta-carotene hydroxylase in addition to a beta-carotene ketolase, in the transgenic seeds suggests that an endogenous soybean enzyme is able to work in combination with the ketolase transgene. Soybean seeds that accumulate ketocarotenoids could potentially be used in animal feed to reduce or eliminate the need for the costly addition of these compounds. PMID- 26376483 TI - Use of an Inverse Method for Time Series to Estimate the Dynamics of and Management Strategies for the Box Jellyfish Carybdea marsupialis. AB - Frequently, population ecology of marine organisms uses a descriptive approach in which their sizes and densities are plotted over time. This approach has limited usefulness for design strategies in management or modelling different scenarios. Population projection matrix models are among the most widely used tools in ecology. Unfortunately, for the majority of pelagic marine organisms, it is difficult to mark individuals and follow them over time to determine their vital rates and built a population projection matrix model. Nevertheless, it is possible to get time-series data to calculate size structure and densities of each size, in order to determine the matrix parameters. This approach is known as a "demographic inverse problem" and it is based on quadratic programming methods, but it has rarely been used on aquatic organisms. We used unpublished field data of a population of cubomedusae Carybdea marsupialis to construct a population projection matrix model and compare two different management strategies to lower population to values before year 2008 when there was no significant interaction with bathers. Those strategies were by direct removal of medusae and by reducing prey. Our results showed that removal of jellyfish from all size classes was more effective than removing only juveniles or adults. When reducing prey, the highest efficiency to lower the C. marsupialis population occurred when prey depletion affected prey of all medusae sizes. Our model fit well with the field data and may serve to design an efficient management strategy or build hypothetical scenarios such as removal of individuals or reducing prey. TThis This sdfsdshis method is applicable to other marine or terrestrial species, for which density and population structure over time are available. PMID- 26376484 TI - Control of Precision Grip Force in Lifting and Holding of Low-Mass Objects. AB - Few studies have investigated the control of grip force when manipulating an object with an extremely small mass using a precision grip, although some related information has been provided by studies conducted in an unusual microgravity environment. Grip-load force coordination was examined while healthy adults (N = 17) held a moveable instrumented apparatus with its mass changed between 6 g and 200 g in 14 steps, with its grip surface set as either sandpaper or rayon. Additional measurements of grip-force-dependent finger-surface contact area and finger skin indentation, as well as a test of weight discrimination, were also performed. For each surface condition, the static grip force was modulated in parallel with load force while holding the object of a mass above 30 g. For objects with mass smaller than 30 g, on the other hand, the parallel relationship was changed, resulting in a progressive increase in grip-to-load force (GF/LF) ratio. The rayon had a higher GF/LF force ratio across all mass levels. The proportion of safety margin in the static grip force and normalized moment-to moment variability of the static grip force were also elevated towards the lower end of the object mass for both surfaces. These findings indicate that the strategy of grip force control for holding objects with an extremely small mass differs from that with a mass above 30 g. The data for the contact area, skin indentation, and weight discrimination suggest that a decreased level of cutaneous feedback signals from the finger pads could have played some role in a cost function in efficient grip force control with low-mass objects. The elevated grip force variability associated with signal-dependent and internal noises, and anticipated inertial force on the held object due to acceleration of the arm and hand, could also have contributed to the cost function. PMID- 26376486 TI - A Multiscale Vibrational Spectroscopic Approach for Identification and Biochemical Characterization of Pollen. AB - BACKGROUND: Analysis of pollen grains reveals valuable information on biology, ecology, forensics, climate change, insect migration, food sources and aeroallergens. Vibrational (infrared and Raman) spectroscopies offer chemical characterization of pollen via identifiable spectral features without any sample pretreatment. We have compared the level of chemical information that can be obtained by different multiscale vibrational spectroscopic techniques. METHODOLOGY: Pollen from 15 different species of Pinales (conifers) were measured by seven infrared and Raman methodologies. In order to obtain infrared spectra, both reflectance and transmission measurements were performed on ground and intact pollen grains (bulk measurements), in addition, infrared spectra were obtained by microspectroscopy of multigrain and single pollen grain measurements. For Raman microspectroscopy measurements, spectra were obtained from the same pollen grains by focusing two different substructures of pollen grain. The spectral data from the seven methodologies were integrated into one data model by the Consensus Principal Component Analysis, in order to obtain the relations between the molecular signatures traced by different techniques. RESULTS: The vibrational spectroscopy enabled biochemical characterization of pollen and detection of phylogenetic variation. The spectral differences were clearly connected to specific chemical constituents, such as lipids, carbohydrates, carotenoids and sporopollenins. The extensive differences between pollen of Cedrus and the rest of Pinaceae family were unambiguously connected with molecular composition of sporopollenins in pollen grain wall, while pollen of Picea has apparently higher concentration of carotenoids than the rest of the family. It is shown that vibrational methodologies have great potential for systematic collection of data on ecosystems and that the obtained phylogenetic variation can be well explained by the biochemical composition of pollen. Out of the seven tested methodologies, the best taxonomical differentiation of pollen was obtained by infrared measurements on bulk samples, as well as by Raman microspectroscopy measurements of the corpus region of the pollen grain. Raman microspectroscopy measurements indicate that measurement area, as well as the depth of focus, can have crucial influence on the obtained data. PMID- 26376485 TI - Characteristics of Human Turbinate-Derived Mesenchymal Stem Cells Are Not Affected by Allergic Condition of Donor. AB - The characteristics of mesenchymal stem cells (MSCs) derived from human turbinates (hTMSCs) have not been investigated in allergic rhinitis. We evaluated the influence of allergic state of the donor on the characteristics, proliferation, and differentiation potential of hTMSCs, compared with hTMSCs derived from non-allergic patients. hTMSCs were isolated from five non-allergic and five allergic patients. The expression of toll-like receptors (TLRs) in hTMSCs was measured by FACS, and cell proliferation was measured using a cell counting kit. Cytokine secretion was analyzed using multiplex immunoassays. The osteogenic, chondrogenic, and adipogenic differentiation potentials of hTMSCs were evaluated by histology and gene expression analysis. In allergic patients, FACS analysis showed that TLR3 and TLR4 were more highly expressed on the surface of hTMSCs than TLR2 and TLR5. The proliferation of hTMSCs was not influenced by the presence of TLR priming. The expression of IL-6, IL-8, IL-12, IP-10, and RANTES was upregulated after the TLR4 priming. The differentiation potential of hTMSCs was not influenced by TLR priming. These characteristics of hTMSCs were similar to those of hTMSCs from non-allergic patients. We conclude that the allergic condition of the donor does not influence TLR expression, proliferation, or immunomodulatory potential of hTMSCs. PMID- 26376487 TI - The Novel Application of Non-Lethal Citizen Science Tissue Sampling in Recreational Fisheries. AB - Increasing fishing pressure and uncertainty surrounding recreational fishing catch and effort data promoted the development of alternative methods for conducting fisheries research. A pilot investigation was undertaken to engage the Australian game fishing community and promote the non-lethal collection of tissue samples from the black marlin Istiompax indica, a valuable recreational-only species in Australian waters, for the purpose of future genetic research. Recruitment of recreational anglers was achieved by publicizing the project in magazines, local newspapers, social media, blogs, websites and direct communication workshops at game fishing tournaments. The Game Fishing Association of Australia and the Queensland Game Fishing Association were also engaged to advertise the project and recruit participants with a focus on those anglers already involved in the tag-and-release of marlin. Participants of the program took small tissue samples using non-lethal methods which were stored for future genetic analysis. The program resulted in 165 samples from 49 participants across the known distribution of I. indica within Australian waters which was a sufficient number to facilitate a downstream population genetic analysis. The project demonstrated the potential for the development of citizen science sampling programs to collect tissue samples using non-lethal methods in order to achieve targeted research objects in recreationally caught species. PMID- 26376488 TI - Molecular Cloning and Functional Expression of the Equine K+ Channel KV11.1 (Ether a Go-Go-Related/KCNH2 Gene) and the Regulatory Subunit KCNE2 from Equine Myocardium. AB - The KCNH2 and KCNE2 genes encode the cardiac voltage-gated K+ channel KV11.1 and its auxiliary beta subunit KCNE2. KV11.1 is critical for repolarization of the cardiac action potential. In humans, mutations or drug therapy affecting the KV11.1 channel are associated with prolongation of the QT intervals on the ECG and increased risk of ventricular tachyarrhythmia and sudden cardiac death- conditions known as congenital or acquired Long QT syndrome (LQTS), respectively. In horses, sudden, unexplained deaths are a well-known problem. We sequenced the cDNA of the KCNH2 and KCNE2 genes using RACE and conventional PCR on mRNA purified from equine myocardial tissue. Equine KV11.1 and KCNE2 cDNA had a high homology to human genes (93 and 88%, respectively). Equine and human KV11.1 and KV11.1/KCNE2 were expressed in Xenopus laevis oocytes and investigated by two electrode voltage-clamp. Equine KV11.1 currents were larger compared to human KV11.1, and the voltage dependence of activation was shifted to more negative values with V1/2 = -14.2+/-1.1 mV and -17.3+/-0.7, respectively. The onset of inactivation was slower for equine KV11.1 compared to the human homolog. These differences in kinetics may account for the larger amplitude of the equine current. Furthermore, the equine KV11.1 channel was susceptible to pharmacological block with terfenadine. The physiological importance of KV11.1 was investigated in equine right ventricular wedge preparations. Terfenadine prolonged action potential duration and the effect was most pronounced at slow pacing. In conclusion, these findings indicate that horses could be disposed to both congenital and acquired LQTS. PMID- 26376489 TI - Evidence for Multiple Rhythmic Skills. AB - Rhythms, or patterns in time, play a vital role in both speech and music. Proficiency in a number of rhythm skills has been linked to language ability, suggesting that certain rhythmic processes in music and language rely on overlapping resources. However, a lack of understanding about how rhythm skills relate to each other has impeded progress in understanding how language relies on rhythm processing. In particular, it is unknown whether all rhythm skills are linked together, forming a single broad rhythmic competence, or whether there are multiple dissociable rhythm skills. We hypothesized that beat tapping and rhythm memory/sequencing form two separate clusters of rhythm skills. This hypothesis was tested with a battery of two beat tapping and two rhythm memory tests. Here we show that tapping to a metronome and the ability to adjust to a changing tempo while tapping to a metronome are related skills. The ability to remember rhythms and to drum along to repeating rhythmic sequences are also related. However, we found no relationship between beat tapping skills and rhythm memory skills. Thus, beat tapping and rhythm memory are dissociable rhythmic aptitudes. This discovery may inform future research disambiguating how distinct rhythm competencies track with specific language functions. PMID- 26376490 TI - Surface-Tuned Co3O4 Nanoparticles Dispersed on Nitrogen-Doped Graphene as an Efficient Cathode Electrocatalyst for Mechanical Rechargeable Zinc-Air Battery Application. AB - The most vital component of the fuel cells and metal-air batteries is the electrocatalyst, which can facilitate the oxygen reduction reaction (ORR) at a significantly reduced overpotential. The present work deals with the development of surface-tuned cobalt oxide (Co3O4) nanoparticles dispersed on nitrogen-doped graphene as a potential ORR electrocatalyst possessing some unique advantages. The thermally reduced nitrogen-doped graphene (NGr) was decorated with three different morphologies of Co3O4 nanoparticles, viz., cubic, blunt edged cubic, and spherical, by using a simple hydrothermal method. We found that the spherical Co3O4 nanoparticle supported NGr catalyst (Co3O4-SP/NGr-24h) has acquired a significant activity makeover to display the ORR activity closely matching with the state-of-the-art Pt supported carbon (PtC) catalyst in alkaline medium. Subsequently, the Co3O4-SP/NGr-24h catalyst has been utilized as the air electrode in a Zn-air battery, which was found to show comparable performance to the system derived from PtC. Co3O4-SP/NGr-24h catalyst has shown several hours of flat discharge profile at the discharge rates of 10, 20, and 50 mA/cm(2) with a specific capacity and energy density of ~590 mAh/g-Zn and ~840 Wh/kg-Zn, respectively, in the primary Zn-air battery system. In conjunction, Co3O4-SP/NGr 24h has outperformed as an air electrode in mechanical rechargeable Zn-air battery as well, which has shown consistent flat discharge profile with minimal voltage loss at a discharge rate of 50 mA/cm(2). The present results, thus demonstrate that the proper combination of the tuned morphology of Co3O4 with NGr will be a promising and inexpensive material for efficient and ecofriendly cathodes for Zn-air batteries. PMID- 26376491 TI - Physical Examination. PMID- 26376492 TI - ENDOSCOPIC SELF-EXPANDING METAL STENTS FOR MALIGNANT COLONIC BOWEL OBSTRUCTION. PMID- 26376493 TI - A SEVERE CASE OF ADULT ONSET STILLS DISEASE WITH MYOPERICARDITIS, RESISTANT TO TREATMENT WITH TOCILIZUMAB BUT RESPONSIVE TO ANAKINRA. PMID- 26376494 TI - A MULTIVARIATE ANALYSIS OF FACTORS AFFECTING DID NOT ATTEND (DNA) RATES IN A PAEDIATRIC EYE CLINIC: DO WEATHER AND SCHOOL HOLIDAYS AFFECT ATTENDANCE AT PAEDIATRIC EYE CLINIC? PMID- 26376496 TI - YKL-40 and non-small cell lung cancer. Response. PMID- 26376495 TI - NO PAIN NO GAIN? TWO CASES OF SPIN CLASS INDUCED RHABDOMYOLYSIS. PMID- 26376497 TI - RE: Primary Tumor Location as a Prognostic Factor in Metastatic Colorectal Cancer. PMID- 26376498 TI - Authors' response. PMID- 26376499 TI - Authors' response. PMID- 26376500 TI - Case Mix Methodologies. PMID- 26376501 TI - The Hidden Poor: Over Three-Quarters of a Million Older Californians Overlooked by Official Poverty Line. AB - More than three-quarters of a million (772,000) older Californians are among the "hidden poor"--older adults with incomes above the federal poverty line (FPL) but below a minimally decent standard of living as determined by the Elder Economic Security StandardTM Index (Elder Index) in 2011. This policy brief uses the most recent Elder Index calculations to document the wide discrepancy that exists between the FPL and the Elder Index. This study finds that the FPL significantly underestimates the number of economically insecure older adults who are unable to make ends meet. Yet, because many public assistance programs are aligned with the FPL, potentially hundreds of thousands of economically insecure older Californians are denied aid. The highest rates of the hidden poor among older adults are found among renters, Latinos, women, those who are raising grandchildren, and people in the oldest age groups. Raising the income and asset eligibility requirement thresholds for social support programs such as Supplemental Security Income (SSI), housing, health care, and food assistance would help California's older hidden poor make ends meet. PMID- 26376502 TI - Methods in Cell Biology. Centrosome & Centriole. Preface. PMID- 26376504 TI - 2016 exchange rate hikes: how big will they be? PMID- 26376503 TI - Special Report: Chromosomal Microarray for the Genetic Evaluation of Patients With Global Developmental Delay, Intellectual Disability, and Autism Spectrum Disorder. PMID- 26376505 TI - Value-Based Payment Readiness. PMID- 26376506 TI - 5 ways to empower patients during the payment process. PMID- 26376507 TI - From the front line to the bottom line: building revenue integrity. AB - To improve trends in accounts receivable and a hospital's bottom line without fear of penalty or repayment, organizations should expand the definition of the revenue cycle team by: Engaging front-line clinical and business personnel. Training personnel to understand the roles they play in revenue integrity. Creating scorecards with measurable goals to promote accountability. Monitoring the outcomes and defining real-time, actionable responses to negative variances. PMID- 26376508 TI - Implementing value-based physician compensation: advice from early adopters. AB - Provider organizations that have experience in implementing value-based physician compensation can recommend the following best practices, among others: Clearly link changes in physician compensation to the broader strategic and financial objectives of the organization. Focus financial incentives on evidence-based measures that physicians find credible and achievable. Make sure everyone understands the incentive measures and compensation formulas before implementing changes. Provide complete data transparency for all aspects of performance. PMID- 26376509 TI - Successful medical group integration: it's about more than the numbers. AB - Key aspects of integrating a medical group into a health system include: Performing due diligence. Developing a culture of trust. Onboarding new physicians and groups. Dealing with underperforming physicians. PMID- 26376510 TI - Building the right physician platform. AB - The challenges health systems often face in aligning physicians with organizational cost and quality goals related to the delivery of value-based care differ between employed and independent physicians. With employed physicians, the focus should be on right-sizing the service delivery network and employed medical group, building a sustainable compensation program, enhancing the revenue cycle, increasing use of midlevel providers, and implementing a common technology platform. With independent physicians, the focus should be on understanding available contracting models, participating in shared-savings arrangements, considering alternative payment distribution models, choosing the right metrics, and exploring shared branding options. PMID- 26376511 TI - Survive or thrive? Becoming a successful value-based enterprise. AB - Health systems should examine their current value competencies, assess their potential viability in a value-based environment, and prepare to redesign care delivery as needed. To flourish, value-based enterprises should be optimally integrated, scaled, rationalized, informed, and responsive. The process of becoming a value-based enterprise begins with assessing organizational readiness across five domains. PMID- 26376512 TI - Strategies for reconfiguring cost structure: highlights from HFMA's Value Project research. PMID- 26376513 TI - Developing the organizational competencies needed in value-based payment systems. PMID- 26376514 TI - Interrelated metrics provide perspectives on hospital readmission rates. PMID- 26376515 TI - Smilematters. PATIENT FACT SHEET. Diabetes and Oral Health: A Two-Way Street. PMID- 26376517 TI - June Meeting Focuses on MDA Subsidiaries, Member Engagement. PMID- 26376516 TI - Oral Health Care During Pregnancy. PMID- 26376518 TI - When a Parent Is Under the Influence of Drugs. PMID- 26376519 TI - Trust But Verify: The Value of Reference Checks. PMID- 26376520 TI - Thank you contributors. The Keys to MDA Legislative Success. PMID- 26376521 TI - A Mixed Density Lesion in the Anterior Mandible. Adenomatoid odontogenic tumor. PMID- 26376523 TI - Protect Your Family with a Letter of Last Instruction. PMID- 26376522 TI - For the Record. PMID- 26376525 TI - Urinary excretion of brush-border enzymes of the proximal renal tubules in pregnant women with hypertensive disorders. AB - OBJECTIVES: The aim of our study was to evaluate urinary excretion of three brush border enzymes: gamma-glutamyl transferase, alanine aminopeptidase, and leucyl aminopeptidase in pregnant women with various types of hypertensive disorders. MATERIAL AND METHODS: The study included 120 pregnant women, further subdivided into four groups: 41 women at >= 20 weeks gestation with gestational hypertension, 28 women > 20 weeks of pregnancy with preeclampsia, 21 women with chronic hypertension identified > 20 weeks of pregnancy and 30 healthy pregnant controls. RESULTS: No significant differences in urinary levels of all three of the brush border enzymes were found between the groups. Also, there was no correlation between enzyme concentration in the urine and blood pressure values in any of the analyzed groups of pregnant women. CONCLUSIONS: The obtained results suggest no damage to the brush border of the proximal kidney tubules in the early stages of disorders associated with increased blood pressure during pregnancy. PMID- 26376524 TI - [Standardization of the quantitative flow cytometric test with anti-D antibodies for fetomaternal hemorrhage in RhD negative women]. AB - BACKGROUND: In order to determine the appropriate dose of anti-D immunoglobulin to be administered as a preventive measure against hemolytic disease of the fetus/newborn in the subsequent pregnancy it is necessary to assess the number of fetal red blood cells that infiltrate/penetrate into the maternal circulation as a result of fetomaternal hemorrhage (FMH). One of the quantitative methods of FMH analysis is based on flow cytometry (FACS) which makes use of monoclonal antibodies to RhD antigen (anti-D test). The aim of the study was to further develop the method, evaluate its sensitivity and reproducibility and to compare it with the test based on the detection of fetal hemoglobin (HbF). MATERIAL AND METHODS: The FACS study involved 20 RhD negative pregnant women and 80 RhD negative women after delivery. The following monoclonal antibodies were used: BRAD 3 FITC (anti-RhD antigen), CD45 PerCP (anti leukocyte antigen CD45), and anti-HbF PE. RESULTS: The fluorescence intensity of cells incubated with BRAD 3 FITC was demonstrated to depend on the RhD antigen expression, though the anti-D test also detects the weak D variant. The CD45 PerCP antibodies increased the sensitivity of anti-D test since they eliminated the leukocytes which non specifically bind anti-D from the analysis. The presence of anti-D antibodies in maternal plasma does not affect the quantitative assessment of the fetal RhD positive fetal cells with BRAD 3 FITC. In case of FMH, the results of the anti-D test were similar to those with anti-HbF antibodies. CONCLUSIONS: The flow cytometric test with anti-D and anti-CD45 is useful in the assessment of the fetomaternal hemorrhage in RhD negative women. The sensitivity of the test is estimated at 0.05%. PMID- 26376526 TI - Family, anthropometric and biochemical factors affecting birth weight of infants born to GDM women. AB - OBJECTIVES: Gestational diabetes mellitus (GDM) affects up to 25% of all pregnancies worldwide. If untreated, GDM leads to increased complication rates both, in the mother and the fetus. Early diagnosis and adequate management of GDM are essential to avoid macrosomia. Nonetheless, neonates born to GDM mothers often have high birth weight. The aim of the study was to evaluate selected factors which can affect neonatal birth weight. MATERIAL AND METHODS: The study included 152 women with GDM and 58 healthy pregnant controls. Anthropometric data of both parents, maternal biochemical parameters, and neonatal birth weight were collected. RESULTS: The independent factors influencing neonatal birth weight were pregnancy duration, maternal smoking, as well as birth weight and current weight of the father. The risk of delivering a large for gestational age (LGA) infant increases with the diagnosis of GDM, higher maternal pre-pregnancy weight, and higher fasting glycaemia. No correlation between maternal fasting glycaemia, HbA1c, 1,5-AG, lipids and neonatal birth weight was found. CONCLUSIONS: Risk factors for LGA include gestational diabetes, high maternal pre-pregnancy weight, and current body weight of the father. Neither HbA1c nor 1,5-AG were reliable predictors of neonatal birth weight and occurrence of LGA in the studied population. PMID- 26376527 TI - Have we achieved progress in tocolytic treatment?--results of a retrospective cohort study in a tertiary university hospital. AB - OBJECTIVES: Beta-agonists play an important role in tocolytic treatment. In light of recent changes in the Polish medical care system, we decided to assess the effectiveness of oral continuous treatment (in 2012) and compare it with a 3-day intravenous administration of fenoterol (in 2013). The aim of our study was to contrast cost and effectiveness of fenoterol therapy in pregnant women at risk of preterm labor during two consecutive years: 2012 - when fenoterol had been widely used (group A), and 2013 when its extensive use had been withdrawn (group B). MATERIAL AND METHODS: Retrospective cohort study of 129 pregnant women: 76 treated with intravenous fenoterol, followed by continuous oral administration (November 2012; group A), and 53 treated with intravenous fenoterol only for 48 72 hours (November 2013; group B). RESULTS: Perinatal outcomes (based on the Apgar score and neonatal weight) were comparable in both groups. Continuous oral application of fenoterol resulted in earlier gestational age at delivery and lower cost of hospitalization among women from group A as compared to group B. Regardless, the difference was not statistically significant (37 hbd vs. 35 hbd, p = 0.626; 4334,700PLN vs. 5232,470PLN, p = 0.533). CONCLUSIONS: A 3-day intravenous application of fenoterol is as effective as oral continuous therapy and is characterized by reduced risk of negative side effects. PMID- 26376528 TI - Two techniques of pyramidalis muscle dissection in Pfannenstiel incision for cesarean section. AB - OBJECTIVES: The aim of the study was to compare two techniques of pyramidalis muscle dissection during cesarean section. MATERIAL AND METHODS: A total of 108 patients undergoing a cesarean section were randomly allocated to group I (N = 57), with the pyramidalis muscle left attached to the rectus muscles, and group II (N = 51), with preservation of the connection between the pyramidalis muscle and the rectus sheath. RESULTS: There were no statistically significant differences between the groups regarding surgery duration, blood loss and postoperative pain. After three months, patients from group II more frequently reported paresthesia in the scar region (47.1 vs. 28.1%; p = 0.041), but their self-assessment of the abdominal appearance and presence of the bulging below the wound were comparable with group I. CONCLUSIONS: None of the two techniques of pyramidalis muscle dissection appear to be superior to the other. The technique leaving the pyramidalis muscle attached to the fascia gave more frequent paresthesia during a 3-month follow-up. PMID- 26376529 TI - Self-directed learning in high-quality antenatal screening. AB - OBJECTIVES: To compare first-trimester scan results between audited (AS), according to the Fetal Medicine Foundation criteria, and non-audited sonographers (NAS). MATERIAL AND METHODS: Retrospective observational study of N = 629 and N = 1290 NT and CRL measurements done by AS and NAS, respectively. RESULTS: For similar examined populations (similar CRL and maternal age at examination) NT values were significantly lower in NAS with NT of 1.0 mm or less in 26.9% of measurements taken by NAS (vs. 0.3% in AS). NT differed significantly between NAS and AS in all maternal age groups, except for patients below 24 years of age and in all CRL categories. CONCLUSIONS: Training of sonographic skills in fetal medicine needs to be complemented by a regular audit to ensure adequate quality of the measurements. PMID- 26376530 TI - Effects of sildenafil citrate and etanercept treatment on TNF-alpha levels in peripheral blood of women with recurrent miscarriage. AB - OBJECTIVES: The aim of the study was to determine serum concentrations of a proinflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), in patients with recurrent abortions undergoing treatment with sildenafil or etanercept. MATERIAL AND METHODS: Serum TNF-alpha concentrations were determined for 24 patients with recurrent miscarriages (aged 32.7 +/- 4.64 years) deemed eligible for sildenafil therapy and 7 patients treated with etanercept (aged 37.65 +/- 5.45 years). Measurements were performed before and after therapy. The control group included 10 healthy women (aged 33.3 +/- 5.49 years), who gave birth at least once without pregnancy-related complications. The levels of serum TNF-alpha were measured by Elisa. RESULTS: Patients treated with etanercept had significantly elevated levels of TNF-alpha before therapy as compared to the control group (41.4 +/- 28.4 vs. 16.6 +/- 7.2 pg/ml). Moreover we found a tendency for the concentration of TNF-alpha to increase in sera of patients treated with sildenafil after therapy completion (19 +/- 29 vs. 15.4 +/- 26.7 pg/ml). Treatment with etanercept resulted in a significant reduction of serum TNF-alpha levels (41.4 +/- 28.4 vs. 25.4 +/- 3.2 pg/ml). CONCLUSIONS: Therapy of recurrent abortions with anti-TNF-alpha drugs appears to be encouraging. Administration of blockers of phosphodiesterase type 5 or TNF-alpha blockers before conception seems to be a promising future therapy of immune-dependent recurrent miscarriages, limiting the teratogenic influence of the drugs on the fetus. PMID- 26376531 TI - Survivin in ovary tumors. AB - INTRODUCTION: Survivin is a member of the inhibitor of apoptosis protein (IAP) family which are selectively overexpressed in human neoplasms, and its expression has been shown to be connected with cell proliferation. We analyzed survivin expression in ovarian epithelial neoplasms to evaluate its role in the development of ovarian tumors. MATERIAL AND METHODS: Immunohistochemistry assays were conducted in 137 cases (48 ovarian carcinoma, 43 borderline ovarian carcinoma, 46 benign ovarian tumor and 20 samples of normal ovarian tissue of ovarian epithelial neoplasms. Histological types included serous (n = 68) and mucinous (n = 69) tumors. All tumors were reviewed histopathologically and classified according to the WHO criteria. RESULTS: Survivin expression in the group of serous neoplasms was detected in 24.0% (6 of 25) of benign cases, in 60.0% (12 of 20) of borderline tumors, and 91.0% (24 of 47) of ovarian carcinomas. In the group of mucinous tumors, survivin expression was found in 33.5% (7 of 21) of benign cases, 43.5% (10 of 23) of borderline tumors, and 80.0% (20 of 25) of malignant tumors. CONCLUSIONS: Our results demonstrate that survivin overexpression may play a crucial role in the development of epithelial ovarian neoplasms and be an important prognostic factor for the influence of survivin expression on epithelial ovarian cancers. PMID- 26376532 TI - Functional outcomes of polypropylene midurethral sling resection for treatment of mesh exposure/extrusion: Does it lead to a relapse of incontinence? AB - OBJECTIVES: The Burch colposuspension, which was regarded as the gold standard treatment for stress urinary incontinence for several years, has been replaced by minimally invasive sling devices. Although these procedures are simple and minimally invasive, they are associated with complications such as infection, mesh erosion, chronic pain, and de novo detrusor overactivity, which may necessitate surgical resection or tape removal. The aim of the study was to assess urinary function outcomes including continence, after partial resection of suburethral tapes. MATERIAL AND METHODS: Patients were admitted for resection of tape due to extrusion/exposure, between 2011 and 2014. Patients were evaluated with physical examination, transvaginal ultrasound, cough stress test, 24-hour bladder diary, Incontinence Impact Questionnairre-7 form and Urogenital Distress Inventory-6 form. RESULTS: Minimum follow-up time was 2 months after treatment of the tape complication (mean 20, range 2 to 38). Recurrence of incontinence after partial tape resection was observed in 9% (3/32) cases. In two patients due to stress urinary incontinence recurrence repeat anti-incontinence surgery was necessary. Although one patient had suffered from incontinence after resection of tape, she did not desire operation. CONCLUSIONS: The results of this study indicated that preservation of the anti-incontinence effects of slings might not be dependent on the intactness of the sling. Recurrence of incontinence after partial tape resection is uncommon and in the majority of cases this stress incontinence is minimally and does not require repeat operation. PMID- 26376533 TI - Agreement between colposcopy results using the Reid Colposcopic Index and histopathology. AB - OBJECTIVES: The aim of the study was to evaluate the diagnostic efficacy of colposcopy and to determine the strength of correlation between colposcopic impression using the Reid Colposcopic Index (RCI) and histopathology MATERIAL AND METHODS: This was a prospective cross-sectional study carried out at the colposcopy clinic of Bakirkoy Dr Sadi Konuk Education and Research Hospital, Department of Obstetrics and Gynecology, between June 2011 and September 2011. A total of 105 women who met the selection criteria were included in the study. All women underwent colposcopy and the final diagnosis was made using RCI. Colposcopy guided biopsy was obtained from the abnormal areas. In cases when colposcopy did not reveal any lesion, a four-quadrant biopsy from the squamocolumnar junction was taken, which served as the gold standard. RESULTS: According to the Reid scoring system, there were 60% of benign cases, whereas 27.6%, 5.7%, and 6.7% of the women were diagnosed with CIN 1, CIN 2, CIN 3, respectively As far as histologic results were concerned, 62.9% of the subjects were benign, whereas 25.7%, 3.8%, and 7.6% of the patients were diagnosed with CIN 1, CIN 2, CIN 3, respectively. The correlation between the Reid scoring system and histologic results was statistically significant (p > 0.05). CONCLUSIONS: The correlation between colposcopic lesions graded with RCI and histology was strong, particularly in women who had HGSIL on a Pap smear. Good correlation between colposcopic imaging using RCI and histopathology makes it a reproducible technique, easy to implement in colposcopy clinics. PMID- 26376534 TI - [Human papilloma virus genotyping in women with abnormal cytology]. AB - OBJECTIVE: To assess presence of HPV infection and identification of the most common HPV types in patients with abnormal cytology based on the Bethesda system (atypical squamous cells). MATERIAL AND METHOD: 81 women with abnormal cytology based on the Bethesda system (atypical squamous cells) were qualified for the study. Material was taken from the cervical canal, the vaginal portion of the cervix and the vagina onto a liquid medium to detect HPV DNA and genotyping of 19 most common oncogenic types of high and medium risk was performed with the Papillomastrip method and for HPV types 6 and 11 with the PCR method. RESULTS: HPV was detected in 53 out of 81 examined women, which accounted for 66%. The most common HPV types were: 6/11 - 23 cases (43% of women with infection), 16 - 23 cases (43% of women with infection), 18 and 33 with 9 cases each (17% of women with infection). Coexistence of 6/11 with 16 or 18 - 13 concerned 15 patients (28% of women with infection) and presence of HPV 16 or 18 was detected in 28 cases (53% of women with infection). Positive HPV type contained in the quadrivalent vaccine against human papillomavirus 6/11 and 16 or 18 was detected in 38 patients (72% of women with infection). 40% of HPV positive women were infected with only one type of the virus, 26%--with two types and 23% with three types. CONCLUSION: In 81 women with abnormal cytology based on the Bethesda system (atypical squamous cells) within 66% of HPV positive results the most common were type 6/11 (of low oncogenic potential but responsible for anogenital warts) and type 16 of high oncogenic potential. PMID- 26376535 TI - Endometriosis and carcinosarcoma--a hypothetical correlation or a proven pathogenetic pathway? Colon carcinosarcoma with origin in endometriotic foci--a case report. AB - We present the first case of a patient with a synchronic occurrence of three neoplasms: non-small cell lung cancer serous cancer of the ovary and carcinosarcoma of the colon. Moreover, the possible origin of the carcinosarcoma is an endometriotic focus, which is an extremely rare occurrence, especially in women with no history of endometriotic treatment. Immunohistochemical staining of the carcinosarcoma was positive for CD10, estrogen receptors and desmin--typical markers for endometriotic foci. The growth of endometriosis depends on estrogen, which is produced at reduced levels after menopause. However, in some cases endometriosis could be diagnosed de novo in postmenopausal women. On the basis of the reported patient we discuss possible correlations between endometriosis and carcinosarcoma, as well as treatment methods of carcinosarcoma. PMID- 26376537 TI - [Lacerations]. PMID- 26376536 TI - [Polish Gynecological Society--Ultrasound Section Guidelines on ultrasound screening in uncomplicated pregnancy--2015]. PMID- 26376538 TI - [Herbal medicines against urinary tract infections--traditional empiricism or pharmacological evidence?]. AB - Empirically, a variety of plants are used for uncomplicated urinary tract infections. The variety of phytopharmaceuticals with valid results is much smaller. There is a variety of observational studies about Cranberry, bearsgrape leaves, birch leaves and European goldenrod. This also justifies a recommendation in the pharmacy in a complementary medical treatment. Desireably, larger placebo controlled studies, which proove the empirical healing, would provide more evidence. Children, pregnant women, men and patients with fever, severe cramps and blood in the urine should not medicate themselve. The patient should be referred to a doctor. PMID- 26376539 TI - [Wound management for cuts and lacerations]. AB - Skin cuts and lacerations are frequent injuries. A perfect result of the treatment is going without saying for the patient and its relatives. But there are some aspects to note for an adequate wound management. The main aims of wound management are clear: assist in hemostasis, to avoid infection and pain, and to ensure an esthetically pleasing scar. For these we have to treat not only the wound. Taking care for the hole patient and treating the sore pain and preventing painfull manipulations is the goal for the patients satisfaction. The basic aspects of wound healing and wound management will be described. Sutures, tissue adhesives, staples, and skin-closure tapes are options in the outpatient setting. Although suturing is the preferred method for laceration repair, tissue adhesives are similar in patient satisfaction, infection rates, and scarring risk in low skin-tension areas and may be also more cost-effective. Patient education and appropriate procedural coding are important after the repair. Please do not forget in every case to ask for the tetanus immunization and to think about an antibiotic therapy in case of human or animal bites and for wounds in risk areas and with contamination. PMID- 26376540 TI - [Tetanus and Clostridium tetani--a brief review]. AB - Tetanus is an acute, often fatal, disease caused by an exotoxin (tetanospasmin) produced by the anaerobic, gram-positive spore-forming bacterium Clostridium tetani. It is characterized by generalized rigidity and convulsive spasms of skeletal muscles. In most industrialized countries, tetanus is a rare disease. However, in many tropical and subtropical countries with low vaccination coverage and poor medical care, it is still widely distributed. This applies in particular for neonatal tetanus. About 50 000 newborns and infants die each year from consequences from this severe illness. Management of tetanus involves neutralization of free circulating toxin, adequate antibacterial and symptomatic therapy as well as intensive care of the patient. For prophylaxis of the disease, active tetanus toxoid vaccination is the method of choice. PMID- 26376541 TI - [Four numbers and a bit more basic knowledge of mathematics]. AB - In addition to relative risk, relative risk reduction and absolute risk reduction there circulates another effect size for binary endpoints in the scientific medical literature: the odds ratio. Relative risk and odds ratio are alternative ways of reflecting study results. Both, relative risk (RR) and odds ratio (OR), can easily be calculated from the "2 x 2-table". Advantage of OR: odds ratios can be calculated in every type of controlled study design, including retrospective studies. Furthermore, odds ratios--the biostatisticians are swarming--offer beautiful mathematical properties and therefore are often used in meta-analysis as an effect size for calculating a pooled estimate of the results of different studies with the same clinical question. Disadvantage of OR: In clinical studies the presentation of the results as "odds ratios" may result in an overestimation of the intervention effect. This article shows the difference between ""chance" and "risk" and how odds ratio and relative risk are associated. PMID- 26376542 TI - [New active substances expand the treatment options for MS]. PMID- 26376543 TI - [Pregnancy and cancer treatment]. PMID- 26376544 TI - [Gene expression tests can avoid unnecessary chemotherapy]. PMID- 26376545 TI - [Clonal hematopoiesis and blood cancer increases with increasing age]. PMID- 26376546 TI - [Side effects of HMG-CoA Reductase inhibitors in placebo-controlled trials ]. PMID- 26376547 TI - [New therapeutic approaches are in the clinical trial]. PMID- 26376548 TI - [Ranibizumab treatment scheme flexibility]. PMID- 26376549 TI - [New data demonstrate benefits of early adjunctive therapy]. PMID- 26376551 TI - Professionalism Under Strain. PMID- 26376550 TI - New Laws for Healthcare Providers. PMID- 26376552 TI - Job Shadowing for Pre-Med Students. Hendrix College Program a Win-Win for Students and Physicians. PMID- 26376553 TI - "The Scalpel or the Needle for Superior Vena Cava syndrome"? AB - Acute Superior Vena Cava (SVC) syndrome from thrombosis is an increasingly recognized complication of intravascular devices. We present a 31 year old woman with an infusion port placed for chemotherapy who developed acute SVC obstruction. A computerized tomograpy (CT) of chest revealed an occlusive thrombus within the SVC extending into the right atrium. Catheter-guided thrombolysis and surgical thrombectomywere felt to impose prohibitive risks. Worsening symptoms led to the use of systemic thrombolysis with tissue plasminogen activator (t-PA) leading to dramatic improvement in symptoms. A repeat CT revealed a reduction of the right atrial thrombus and SVC occlusion had resolved. PMID- 26376554 TI - Patient Centered Medical Home Quality Assurance--Validation. PMID- 26376556 TI - Squamous Cell Carcinoma of Pancreas: Mystery and Facts. AB - Squamous cell carcinoma of the pancreas is very rare as pancreas does not have any squamous cells. Only a few cases have been reported in the literature so far. We describe such a case where in the patient presented with painless jaundice. CT and EUS confirmed the pancreatic mass biopsy of which showed squamous cell cancer. PMID- 26376555 TI - Stress Ulcer Prophylaxis use in the Intensive care Unit before and after House Staff Education. AB - PURPOSE: We hypothesize that stress ulcer prophylaxis with acid suppressant medications (ASM) is overused and educating house-staff will decrease this. METHODS: Retrospective chart review in two six-month phases. House staff was educated prior to phase II. Rates of SUP were calculated for ICU stay, medicine floor, and at discharge. RESULTS: There were 625 ICU admissions. Analysis was done on 106 and 118 patients in each phase. SUP use decreased from 62% to 37% in patients with no indications (p value < 0.01). CONCLUSION: Education can have a significant impact on the appropriate use of medications. Even after this significant decrease, rates of inappropriate usage could be considered unacceptable. PMID- 26376557 TI - A Rare Presentation of Massive Right Atrial Myxoma Causing Constitutional Symptoms: A 20 Year Follow-Up. PMID- 26376558 TI - [New Myriad of summer-time clinical cases]. PMID- 26376559 TI - [Left ventricular non compaction: A poorly known cardiomyopathy]. AB - Left ventricular non compaction is a rare congenital cardiomyopathy. It is characterised by a thin compacted epicardial layer, prominent trabeculations and deep recesses that communicate with the left ventricular cavity. This condition may lead to chronic heart failure, life threatening ventricular arrhythmias and systemic embolic events. PMID- 26376560 TI - [A case of fetal death resulting from a massive fetomaternal hemorrhage]. AB - We report the case of a late stillbirth which unexpectedly occurred in a patient without any medical history and after a meticulous obstetrical follow up. Stillbirth is unfortunately not unusual and implies a complete etiological work up. In the present observation, the Kleihauer test and anatomoclinical examination concluded that the death was due to an acute cerebral anoxy resulting from a massive fetomaternal hemorrhage (HFM). HFM is rarely considered as the cause of a late stillbirth, but its occurrence is certainly underestimated. Yet, if HFM is identified before fetal death, an .adequate management could considerably improve the fetal prognosis and, sometines, save the child's life. PMID- 26376561 TI - [pericarditis following 5-fluorouracil administration]. AB - We report a case of pericarditis supervening after 5-fluorouracil infusion in a 52-year-old patient suffering from metastatic rectal cancer. Besides its well known side-effects (mucitis, diarrhea, nausea, hematotoxicity), this molecule sometimes induces cardio-toxicity, which can take different clinical forms, pericarditis being one of the most uncommon. Several risk factors have been described and have to be kept in mind when initiating this therapy. Prevention may consist of close monitoring of patients considered at risk. Treatment of 5-FU induced cardiotoxicity basically consists in stopping the use of this drug and replacing it with another chemotherapy agent. PMID- 26376562 TI - [Hemoptysis in an elderly man with RENDU-Osler-Weber disease]. AB - Rendu-Osler-Weber disease, also known as hereditary haemorrhagic telangiectasia, is a genetic disease characterized by an autosomal dominant transmission that causes multiple angiodysplasic lesions, and multiple arteriovenous malformations. Among these, pulmonary arteriovenous malformation is the most common, and is found in approximately 70% of patients that suffer from this syndrome. In a representative population sample, it is recognized that 90% of the patients that have a pulmonary arteriovenous malformation suffer in fact from Rendu-Osler-Weber disease. This article presents the case of an 85 year-old man that, in the course of a pulmonary infection, develops haemoptysis and epistaxis, and in whom a voluminous pulmonary arteriovenous malformation is discovered. PMID- 26376563 TI - [Negative pressure pulmonary oedema and pulmonary haemorrhage following upper airway obstruction]. AB - Although well described in the literature, negative pressure pulmonary oedema is an uncommon and often unrecognized pathology. It dramatically develops in healthy subjects, following a sudden obstruction of the upper airway. The strongly negative intra thoracic pressures developed during the inspiratory efforts is then responsible for the formation of pulmonary oedema secondary to increased pulmonary blood volume and hydrostatic pressure. In rare cases, alveolar hemorrhage is observed due to rupture of the alveolar-capillary barrier. This condition is illustrated by the case of a 6 year old child who presented an obstruction of the upper airway in the aftermath of inhaling an inflatable balloon. The evolution was rapidly favorable. PMID- 26376564 TI - [When diagnostic imaging is misleading: a case of subacute liver failure]. AB - We report the case of a 67 year old woman presenting with a mixed alteration of liver function tests. Despite normal results of tomodensitometry and positon emission tomography, a liver biopsy was performed due to the development of acute liver failure: it showed a diffuse infiltration of liver sinusoids by a breast adenocarcinoma, unfortunately fatal for the patient. The tumour infiltration was responsible for portal hypertension and hepatic perfusion disorders leading to liver failure. PMID- 26376565 TI - [Budd-Chiari syndrome: a case report and review of the literature]. AB - We report the history of a 20-year-old woman admitted for thrombosis of the sus hepatic veins and of the inferior vena cava (IVC) with extension of the thrombus into the right atrium. The etiological research was negative and a diagnosis of idiopathic Budd-Chiari syndrome was retained. In view of the absence of vein repermeabilisation under adequate anticoagulant therapy, a venous thrombectomiy was performed under cardiopulmonary bypass, which improved the hepatic venous drainage. Budd-Chiari syndrome is a very serious disorder. Its treatment implies a step by step procedure. An effective anticoagulation must first be established. The complications of portal hypertension then require attention. For a symptomatic patient, one should assess the possibility of restoring the venous permeability, improving the hepatic drainage and decompressing the liver by radiological interventional or surgical procedures. Finally, an hepatic transplantation should be considered in case of treatment ineffectiveness, of fulminant hepatic failure, or of an evolution towards cirrhosis. PMID- 26376566 TI - [Ulcerated duodenitis revealing Henoch-Schonlein purpura]. AB - Inflammation and duodenal ulcers can meet many etiologies. We report the case of a young adult with an ulcerated duodenitis revealing Henoch-Schonlein purpura. The abdominal symptoms preceded the emergence of the classical cutaneous signs of the disease. PMID- 26376567 TI - [Alpha interferon induced hyperthyroidism: a case report and review of the literature]. AB - Treatment with alpha interferon in hepatitis C triggers a thyroid autoimmunity in a variable percentage of cases (2-8%). This complication raises some questions about its screening, the possibility to continue anti-viral therapy and thyroid treatment. Alpha interferon has an immunomodulatory effect on the thyroid, but also an inhibitory effect on thyroid hormone synthesis. This explains the occurrence of cases of thyroid dysfunction, which often remain undetected because of their latency. Factors predicting thyroid dysfunction with interferon use are: female sex, history of thyroid disease and previous autoimmunity. Several clinical aspects are encountered including hypothyroidism (the most frequent depending on the series) and hyperthyroidism related to Graves' disease. For their detection, a cooperation between general practionners, gastroenterologists and endocrinologists is mandatory thyroid function tests are requested before, during and after treatment,with alpha interferon. Therapeutic aspects of thyroid disorders range from simple monitoring to symptomatic treatment, such as thyroxine prescription in the presence of hypothyroidism. Antithyroid drugs radioactive iodine or thyroid surgery are used in cases of severe or persistent Graves' disease induced by alpha interferon. PMID- 26376568 TI - [Mycobacterium kansasii lung infection]. AB - The incidence of non tuberculosis mycobacterial (NTM) pulmonary diseases is increasing. Patients with NTM disease usually suffer prolonged periods of clinical illness prior to diagnosis. An etiological treatment, initiated by a well informed clinician and based on presumptive evidence, can be successful in a significant proportion of cases. PMID- 26376569 TI - [The anterior tarsal tunnel syndrome: a case report]. AB - The anterior tarsal tunnel syndrome is a rare entrapment neuropathy of the deep peroneal nerve beneath the inferior extensor retinaculum of the ankle. It is frequently unrecognized and may lead to misdiagnosis and delayed treatment. We report the case of a 77 year old patient complaining of symptoms of an anterior tarsal tunnel syndrome with neuropathic pain located at the dorsal part of the foot, without any sensorimotor loss. The ENMG was in favour of a motor impairment of the deep peroneal nerve. MRI exploration of the ankle showed a millimetric bony overgrowth of the upper pole of the navicular bone, irritative to the deep peroneal nerve. Infiltration at overgrowth of the navicular provided a partial and temporary decrease in pain symptoms. Surgical nerve decompression was then considered. PMID- 26376570 TI - Aviation, Attorneys, and Constructive Disequilibrium. PMID- 26376571 TI - Interprofessional Intervention to Support Mature Women: A Case Study. AB - Understanding the impact interprofessional teamwork has on patient outcomes is of great interest to health care providers, educators, and administrators. This article describes one clinical team, Women's Health Specialists, and their implementation of an interprofessional health intervention course: "Mindfulness and Well-being: The Mature Woman" (MW: MW) to support mature women's health needs in midlife (age 40-70 years) and empower patient involvement in self-care. The provider team works to understand how their interprofessional education and collaborative practice (IPECP) interventions focused on supporting midlife women are associated with improved quality and clinical outcomes. This case study describes the work of the Women's Health Specialists clinic in partnership with the National Center for Interprofessional Education and Collaborative Practice to study the impact an interprofessional team has on the health needs of women in midlife. This article summarizes the project structure, processes, outputs, and outcomes. Data collection, analysis, strategy, and next steps for future midlife women's projects are also discussed. PMID- 26376572 TI - Building a Health Care Legal Partnership Learning Collaborative. AB - Many Americans need both health care and legal interventions to maximize their opportunities for health. Medical-legal partnerships (MLPs), also known as health care legal partnerships (HLPs), bring the power of law to health care to reduce barriers and negative social determinants of health. The two terms--HLP and MLP- are used interchangeably in this article. Growing research shows that these partnerships can improve care, improve health, enhance interprofessional collaboration, and improve the financial status of patients and providers. HLPs take many forms, depending on their settings and resources. A health care legal partnership learning collaborative that brings leaders of diverse HLPs together to share experiences and best practices can help expand this effective model and enhance its potential for collective impact in improving population health. PMID- 26376573 TI - Enhancing Nurse-Resident Physician Partnerships. AB - Literature has long suggested that collaboration and interprofessional communication are associated with improved provider satisfaction, patient satisfaction, and the provision of individualized care. More recent literature has documented the favorable influence of a collaborative culture on patient outcomes. In response to the growing need for enhanced nurse-physician partnership and recognition of its impact on the patient experience, nurses are designing unit-based programs to bring the two professions together for opportunities to enhance partnership. This article discusses two approaches to enhancing nurse-resident physician partnership introduced by Benike and Clark (2013) and identifies common elements that were critical to the programs' success. PMID- 26376574 TI - Interprofessional Clinical Assignments: A Project in Nursing Education. AB - Education involving interprofessional activities helps to improve learning and the ability to work in an effective collaborative environment. In this project, 16 baccalaureate nursing students were given the opportunity to work with other members of the health care team to develop an understanding of the roles and responsibilities of each group of professionals and the communication skills needed to provide quality and safe care to patients and to positively impact their motivation to work with members of other health professions. All the students in the group documented the successful completion of these objectives in their journals. PMID- 26376575 TI - Enriching the Student Experience Through a Collaborative Cultural Learning Model. AB - This article provides a knowledge and understanding of an international, collaborative, cultural learning model for students from the United States and Scotland. Internationalizing the student experience has been instrumental for student learning for the past eight years. Both countries have developed programs that have enriched and enhanced the overall student learning experience, mainly through the sharing of evidence-based care in both hospital and community settings. Student learning is at the heart of this international model, and through practice learning, leadership, and reflective practice, student immersion in global health care and practice is immense. Moving forward, we are seeking new opportunities to explore learning partnerships to provide this collaborative cultural learning experience. PMID- 26376576 TI - Cultural Immersion as a Strategy for Empowerment. AB - Cultural immersion experiences offered through study abroad opportunities for nursing students have been increasing in recent years. Examining the impact of these experiences has largely focused on students and not on the faculty leading the experiences. It is important to understand the impact of these experiences on all participants. Exploring the literature on empowerment provides some clarity on the relationship between studying abroad and its impact on participants. Further research linking cultural immersion experiences with empowerment is needed to better understand this relationship and the possibilities of empowering both students and faculty engaged in these exciting opportunities. PMID- 26376577 TI - Knowing Your Preference: The Nexus of Personality and Leadership. AB - Prelicensure nursing students must be prepared to address the new challenges that will confront them in the modern health care environment. Leadership development, the gaining of tools and education about the process of influencing and persuading others, is important when working with groups and teams in the work place. Recognition of one's personality preferences using self-assessment is a critical dimension of leadership development. This study examined the personality preferences of a cohort of prelicensure nursing students (N = 14) enrolled in an 18-month leadership program. Students completed the Myers-Briggs assessment before starting and at the completion of the program. Through active student centered learning and experiential exercises, students became more aware of how they preferred to relate to others and how this might affect their work in groups and leading interprofessional teams. The most prominent personality type for both pre- and postassessment was extroversion, sensing, thinking, and judging. PMID- 26376578 TI - Partnerships With Aviation: Promoting a Culture of Safety in Health Care. AB - According to the Institute of Medicine (IOM, 1999, p. 1), "Medical errors can be defined as the failure of a planned action to be completed as intended or the use of a wrong plan to achieve an aim." The current health care culture is disjointed, as evidenced by a lack of consistent reporting standards for all providers; provider licensing pays little attention to errors, and there are no financial incentives to improve safety (IOM, 1999). Many errors in health care are preventable. "Near misses" and adverse events that do occur can offer insight on how to improve practice and prevent future events. The aim of this article is to better understand underreporting of errors in health care, to present a model of change that increases voluntary error reporting, and to discuss the role nurse executives play in creating a culture of safety. This article explores how high reliability organizations such as aviation improve safety through enhanced error reporting, culture change, and teamwork. PMID- 26376579 TI - Conversations Change People and People Change the World. AB - Nursing salons are casual gatherings where nurses from all walks of life and areas of practice engage in thoughtful conversations about the nursing profession. PMID- 26376580 TI - Introducing Viewpoints in The Journal of Physical Chemistry A/B/C. PMID- 26376581 TI - Semicontinuum Solvation Modeling Improves Predictions of Carbamate Stability in the CO2 + Aqueous Amine Reaction. AB - Quantum chemistry computations with a semicontinuum (cluster + continuum) solvation model have been used to cure long-standing misprediction of aqueous carbamate anion energies in the industrially important CO2 + aqueous amine reaction. Previous errors of over 10 kcal mol(-1) are revealed. Activation energies were also estimated with semicontinuum modeling, and a refined discussion of the competing hypothetical mechanisms for CO2 + monoethanolamine (MEA) is presented. Further results are also presented to demonstrate that the basicity of an amine (aqueous proton affinity) correlates only with CO2 affinity within an amine class: secondary amines have an extra CO2 affinity that primary amines do not have. PMID- 26376582 TI - Corrigendum. PMID- 26376583 TI - Reversible Carbene Formation in the Ionic Liquid 1-Ethyl-3-Methylimidazolium Acetate by Vaporization and Condensation. AB - The role of N-heterocyclic carbenes in the chemistry of ionic liquids based on imidazolium salts has long been discussed. Here, we present experimental evidence that 1-ethyl-3-methylimidazolium-2-ylidene (EMIm) can coexist with its protonated imidazolium cation (EMImH(+) ) at low temperatures. If the vapor of the ionic liquid [EMImH(+) ][AcO(-) ] is trapped in solid argon or nitrogen at 9 K, only acetic acid (AcOH) and the carbene, but no ionic species, are found by IR spectroscopy. This indicates that during the evaporation of [EMImH(+) ][AcO(-) ] proton transfer occurs to form the neutral species. If the vapor of [EMImH(+) ][AcO(-) ] is trapped at 9 K as film in the absence of a host matrix, a solid consisting of EMImH(+) , EMIm, AcO(-) , and AcOH is formed. During warming to room temperature the proton transfer in the solid to form back the IL [EMImH(+) ][AcO(-) ] can be monitored by IR spectroscopy. This clearly demonstrates that evaporation and condensation of the IL [EMImH(+) ][AcO(-) ] results in a double proton transfer, and the carbene EMIm is only metastable even at low temperatures. PMID- 26376584 TI - Emerging therapeutic approaches in renal cell carcinoma. AB - In the past decade, targeted therapy with VEGF and mTOR inhibition has significantly improved the outcome of renal cell carcinoma. However, the management of metastatic renal cell carcinoma still remains challenging as most patients eventually progress on targeted therapy, and long-term survivors are still relatively uncommon. There has recently been a resurgence of interest in cancer immunotherapy with the development of checkpoint inhibitors. Here we discuss the best methods to optimize the current standard of care with targeted therapy, and describe select emerging targeted therapies and immunotherapies with anti programmed death-1 pathway inhibitors in the management of metastatic renal cell carcinoma. PMID- 26376585 TI - Prospective Audit of Blood Donor Selection Process in a Tertiary Care Hospital of a Developing Country. AB - OBJECTIVE: The aim of this study was to emphasize the significance of internal audits of the blood donor selection process and documentation in a resource limited country by assessing compliance with the established protocols, and to identify weak areas in the process. MATERIALS AND METHODS: This audit reviewed the donor selection process at the blood bank of Liaquat National Hospital & Medical College, Karachi, over a 6-month period. Seven variables selected as performance indicators were graded as very good (%90-100%), good (80%-89%), satisfactory (70%-79%), or unacceptable (<70%). Blood bank staff was asked for feedback and suggestions. RESULTS: Documentation of donor demographics was not within the acceptable range (documentation rates of 65.14%), donor status records were satisfactory (77.64%), and donor physical exam records were graded as good (86.34%). Five performance indicators were graded as very good (90%-100%). CONCLUSION: The audit proved productive in identifying major causes of irregularities in documentation and in making valuable suggestions for their rectification. PMID- 26376587 TI - Spontaneous mirror symmetry breaking in a re-entrant isotropic liquid. AB - An achiral double-swallow tailed tetracatenar compound forms a re-entrant isotropic liquid between a bicontinuous cubic phase and a nematic liquid crystalline phase. This isotropic liquid was found to represent a conglomerate of two immiscible chiral liquids. The chirality is retained and eventually becomes uniform at the transition to the cubic I432 phase. PMID- 26376586 TI - Waist circumference, visceral abdominal fat thickness and three components of metabolic syndrome. AB - OBJECTIVE: The relationships between the waist circumference (WC), visceral adipose tissue (VAT) thickness and three components of metabolic syndrome (MetS) were explored to verify which of the obesity indices might be superior. METHODS: A cross-sectional study was conducted of 1256 subjects (840 males and 416 females) aged 26-89 years, who were individuals undergoing intensive health checkup. The three components of MetS examined were high blood pressure, glucose intolerance and dyslipidemia. Receiver-operating characteristic (ROC) curve analysis and multiple logistic regression analysis were used for the analyses. RESULTS: The mean values of the WC and VAT thickness were significantly higher in the subject group positive for each of the metabolic syndrome components than in the subject group that was negative for all the components (p<0.001). ROC curve analysis showed that the WC showed an advantage over the VAT thickness only for predicting high blood pressure in men. Logistic regression analysis revealed increase of the odds ratios of the WC for glucose intolerance (p<0.001), high blood pressure (p<0.001) and dyslipidemia (p<0.01) in men. In contrast, the odds ratio of the VAT thickness was significantly increased only for dyslipidemia (p<0.01) in men. In women, the odds ratios of the WC for glucose intolerance (p<0.01) and dyslipidemia (p<0.001) were significantly increased, and odds ratio of the VAT thickness for high blood pressure (p<0.01) was significantly increased. CONCLUSION: This survey presented an advantage of WC over VAT thickness as an obesity index for identifying all the three components of metabolic syndrome, although sex differences in the study outcomes were found. PMID- 26376588 TI - The Prognostic Significance of Soluble Urokinase Plasminogen Activator Receptor in Acute Myeloid Leukemia. AB - OBJECTIVE: The soluble urokinase plasminogen activator receptor (suPAR) is a soluble form of the urokinase plasminogen activator receptor expressed in various immune and cancer cells. The levels of suPAR have been demonstrated to correlate with prognosis in various cancers. This study was intended to investigate serum suPAR levels and their effect on prognosis in patients with acute myeloid leukemia (AML). MATERIALS AND METHODS: Thirty newly diagnosed patients with AML and 29 healthy individuals were enrolled. Serum suPAR levels were analyzed by enzyme-linked immunosorbent assay. RESULTS: Serum suPAR levels were significantly higher in patients with AML than in healthy individuals (9+/-5.9 ng/mL and 2.4+/ 1.4 ng/mL, respectively; p<0.001). Positive correlation was determined between suPAR levels and white blood cell counts (p<0.01). Serum suPAR levels were lower in patients who achieved complete response than in patients not achieving complete response (5.5+/-2.2 ng/mL and 12+/-6.6 ng/mL, respectively; p<0.001). The median overall survival was longer in patients with serum suPAR levels below 6.71 ng/mL than in those with serum suPAR levels above 6.71 ng/mL (12.6+/-13.2 months and 1.71+/-0.6 months, respectively; p=0.02). Multivariate Cox regression analysis showed that suPAR had independent prognostic value (95% confidence interval: 1.029-6.259; p<0.05) in AML. CONCLUSION: Serum suPAR levels can be used as a prognostic marker in AML. PMID- 26376589 TI - Molecular organization in freely suspended nano-thick 8CB smectic films. An atomistic simulation. AB - We present an atomistic molecular dynamics simulation of freely suspended films of the smectic liquid crystal 8CB formed by nl = 2, 3,...,10, 20 theoretical monolayers, determining their orientational and positional order as a function of the film thickness. We find that films are always composed by bilayers of antiparallel molecules, and that in the case of odd nl, the system prefers to self-assemble in (nl + 1)/2 bilayers, with an increase of surface tension with respect to even nl samples. We also show that external layers have higher positional and orientational order, and that upon heating the disordering of the system proceeds from the inside, with the central layers progressively losing their smectic character, while the external ones are more resistant to temperature changes and keep the film from breaking. PMID- 26376590 TI - Infections in Hospitalised Patients with Multiple Myeloma: Main Characteristics and Risk Factors. AB - OBJECTIVE: Multiple myeloma is a common haematological malignancy and immune dysfunction is the hallmark of the disease. It leads to an increased infection risk, which is still a major cause of mortality. The infection spectrum and characteristics have evolved with the introduction of novel agents. An understanding of risk factors that increase susceptibility to infections is critical in fighting them. This retrospective investigation aimed to establish the incidence and main characteristics of infections in non-transplanted hospitalised myeloma patients in our department over a 3-year period, as well as factors associated with infections. MATERIALS AND METHODS: A total of 240 hospitalised patients with multiple myeloma (120 males and 120 females; average age: 69 years, range: 41-89 years) who were diagnosed or treated in our department from January 2008 to December 2010 were included in this study and their data were retrospectively analysed. RESULTS: Infections were identified in 17.9% of hospitalised patients. The most common pathogen found was Pseudomonas aeruginosa. The frequency of gram-positive and gram-negative pathogens was similar. In 37.2% of cases, the agent was not isolated. The most common sites of infections were the urinary system and the blood (septicemia). The frequency of infection increased with duration of disease and the rate of reinfection was 41.9%. The patients treated with bortezomib had the highest infection occurrence. Fatal outcome occurred in 9.3% of cases. CONCLUSION: The factors associated with infections in this investigation were female sex, 3B clinical stage of disease, increased serum creatinine and ferritin levels, neutropenia, poor general condition, and presence of catheters. Myeloma patients with one or more of these mentioned risk factors should be monitored with particular care in order to decrease the incidence and severity of infective complications. PMID- 26376591 TI - The Impact of Chemotherapy on Hepatitis B Antibody Titer in Patients with Hematological Malignancies. AB - OBJECTIVE: To investigate the influence of chemotherapy (CT) on HBsAb titer in patients receiving CT due to hematological malignancy. MATERIALS AND METHODS: The data of 75 patients who received CT with the diagnosis of various hematological malignancies and who had serum HBsAb levels measured prior to and after the cessation of CT were evaluated retrospectively. RESULTS: The median age of the patients was 52 years (range: 16-78) with 49 (65%) males and 26 (35%) females. Median HBsAb titer decreased significantly after CT compared to the pre-CT median HBsAb titer [68 (range: 0-1000) vs. 100 (range: 6.2-1000)] (p=0.001). In subgroup analysis, median HBsAb titer decreased significantly after CT in acute leukemia patients [110 (range: 6.2-1000) vs. 67.8 (range: 0-1000)] (p=0.003) and in patients receiving intensive CT [97.2 (range: 6.2-1000) vs. 71 (range: 0-1000)] (p=0.036). The decrease in median HBsAb titer was significant in male patients (p<0.001). HBsAb became negative after CT in 9 patients who were HBcAb-negative and had lower pre-CT HBsAb levels. CONCLUSION: HBsAb decreased after CT, especially in acute leukemia and male patients, and in patients receiving intensive CT. PMID- 26376592 TI - Occurrence of Carcinoma of the Pancreas Following Nilotinib Therapy for Chronic Myeloid Leukemia: Report of a Case with Review of the Literature. AB - The patient, a 79-year-old Japanese man, was diagnosed with the chronic phase of chronic myeloid leukemia and begun on nilotinib therapy in April 2011. The therapeutic response was major molecular response in August. About 19 months after the start of nilotinib therapy at 400 mg/day (November 2012), an adenocarcinoma (24 x 20 mm) confined to the head of the pancreas developed. In February 2013, a pancreaticoduodenectomy was performed. The therapy regimen was switched to dasatinib at 100 mg/day, beginning in April. The response was still major molecular response with no recurrence of pancreatic carcinoma in July 2013. There have been 29 reported cases of secondary neoplasms associated with nilotinib therapy. These secondary neoplasms were characterized by relatively frequent occurrence of papilloma (6 cases), gastric cancer (3 cases), fibroma (3 cases), and thyroid neoplasms (2 cases). The present case, however, is the first to be reported as carcinoma of the pancreas. This report describes the case. PMID- 26376593 TI - Portal Vein Thrombosis of a Newborn with Corrected Total Anomalous Pulmonary Venous Return. AB - Total anomalous pulmonary venous return (TAPVR) is a rare and frequently isolated defect identified in 1% to 3% of all congenital heart diseases. To the best of our knowledge, portal vein thrombosis (PVT) associated with TAPVR has not been reported in the literature. We report a successfully managed PVT in a newborn with infracardiac-type TAPVR and review the literature. Anticoagulation therapies were used during the neonatal period to prevent thrombus progression. PVT should be kept in mind in TAPVR patients who have open heart repair with total correction. The treatment in each neonate should be individualized with consideration of the risk/benefit ratio. PMID- 26376594 TI - Leuconostoc sp. Meningitis in a Patient Treated with Rituximab for Mantle Cell Lymphoma. AB - We present a 64-year-old man who was treated with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemoimmunotherapy for mantle cell lymphoma and developed purulent meningitis, probably caused by Leuconostoc sp. The patient had severe hypogammaglobulinemia, which is a possible complication of rituximab therapy. To our knowledge and after reviewing the available medical literature, this is the first described case of purulent meningitis caused by Leuconostoc sp. in a patient with mantle cell lymphoma that appeared after treatment with the R-CHOP protocol. The diagnosis of purulent meningitis was based on clinical, laboratory and cytological cerebrospinal fluid findings, in addition to blood culture results in which we isolated Leuconostoc sp. The patient was treated with meropenem with full recovery. PMID- 26376595 TI - Thrombotic Microangiopathy with Complement Factor H Gene Mutations Unassociated with Atypical Hemolytic Uremic Syndrome. PMID- 26376596 TI - Rapidly Growing Thyroid Mass: An Unusual Case of Acute Lymphoblastic Leukemia. PMID- 26376597 TI - Auer Rods in Chronic Myelomonocytic Leukemia Can Change the Diagnosis. PMID- 26376598 TI - A Case of Acquired Thrombotic Thrombocytopenic Purpura: Three Recurrences in 25 Years. PMID- 26376599 TI - Rate-dependence of 'wet' biological adhesives and the function of the pad secretion in insects. AB - Many insects use soft adhesive footpads for climbing. The surface contact of these organs is mediated by small volumes of a liquid secretion, which forms thin films in the contact zone. Here, we investigate the role of viscous dissipation by this secretion and the 'bulk' pad cuticle by quantifying the rate-dependence of the adhesive force of individual pads. Adhesion increased with retraction speed, but this effect was independent of the amount of pad secretion present in the contact zone, suggesting that the secretion's viscosity did not play a significant role. Instead, the rate-dependence can be explained by relating the strain energy release rate to the speed of crack propagation, using an established empirical power law. The 'wet' pads' behaviour was akin to that of 'dry' elastomers, with an equilibrium energy release rate close to that of dry van-der-Waals contacts. We suggest that the secretion mainly serves as a 'release layer', minimising viscous dissipation and thereby reducing the time- and 'loading-history'-dependence of the adhesive pads. In contrast to many commercial adhesives which derive much of their strength from viscous dissipation, we show that the major modulator of adhesive strength in 'wet' biological adhesive pads is friction, exhibiting a much larger effect than retraction speed. A comparison between 'wet' and 'dry' biological adhesives, using both results from this study and the literature, revealed a striking lack of differences in attachment performance under varying experimental conditions. Together, these results suggest that 'wet' and 'dry' biological adhesives may be more similar than previously thought. PMID- 26376600 TI - Ticagrelor vs. clopidogrel in Japanese, Korean and Taiwanese patients with acute coronary syndrome -- randomized, double-blind, phase III PHILO study. AB - BACKGROUND: Few data on the relative efficacy and safety of new P2Y12inhibitors such as prasugrel and ticagrelor in Japanese, Taiwanese and South Korean patients with acute coronary syndromes (ACS) exist. METHODS AND RESULTS: The multicenter, double-blind, randomized PHILO trial compared the safety and efficacy of ticagrelor vs. clopidogrel in 801 patients with ACS (Japanese, n=721; Taiwanese, n=35; South Korean, n=44; unknown ethnicity, n=1). All were planned to undergo percutaneous coronary intervention and randomized within 24 h of symptom onset. Primary safety and efficacy endpoints were time to first occurrence of any major bleeding event and to any event from the composite of myocardial infarction, stroke or death from vascular causes, respectively.At 12 months, overall major bleeding occurred in 10.3% of ticagrelor-treated patients and in 6.8% of clopidogrel-treated patients (hazard ratio (HR), 1.54; 95% confidence interval (CI): 0.94-2.53); the composite primary efficacy endpoint occurred in 9.0% and in 6.3% of ticagrelor- and clopidogrel-treated patients, respectively (HR, 1.47; 95% CI: 0.88-2.44). For both analyses, the difference between groups was not statistically significant. CONCLUSIONS: In ACS patients from Japan, Taiwan and South Korea, event rates of primary safety and efficacy endpoints were higher, albeit not significantly, in ticagrelor-treated patients compared with clopidogrel-treated patients. This observation could be explained by the small sample size, imbalance in clinical characteristics and low number of events in the PHILO population. PMID- 26376601 TI - Prognostic Value of Plasma B-Type Natriuretic Peptide in the Long-Term Follow-up of Patients With Transposition of the Great Arteries With Morphologic Right Systemic Ventricle After Atrial Switch Operation. AB - BACKGROUND: B-type natriuretic peptide (BNP) is an established marker for heart failure assessment, but the prognostic quality of BNP after atrial switch operation (ASO) has not yet been elucidated. METHODS AND RESULTS: In 89 patients (median age, 24 years; range, 15-35 years) after ASO, BNP was measured. During a 48-months follow-up we focused on critical cardiac events, defined as decompensation, sudden cardiac death or need for heart transplantation. BNP was considerably lower in 81 patients in functional class (FC) I/II (median, 35 pg/ml; range, 3-586 pg/ml) than in 6 patients in FC III/IV (median, 246 pg/ml; range, 14-1,150 pg/ml, P<=0.073). BNP was significantly higher after Mustard than after Senning procedure (P<=0.030). There was no significant difference in BNP between simple or complex transposition of the great arteries (TGA) (P<=0.44). Eleven subjects (13%, 95% CI: 7-22%) had a critical cardiac event within 48 months. On ROC analysis BNP had a high predictive value regarding discrimination of patients with and without critical events (area under the ROC curve, 0.90; 95% CI: 0.76 to >0.99, P<0.001). The cut-off was 85 pg/ml (sensitivity, 88%; specificity, 85%). Additionally, estimated event-free-survival was longer after Senning than after Mustard procedure (P<=0.017). There was no significant difference in outcome between patients with simple or complex TGA with regard to occurrence of critical events. CONCLUSIONS: BNP is a sensitive and specific prognostic marker for critical cardiac events after ASO. PMID- 26376602 TI - Antimony Doping in Solution-processed Cu2 ZnSn(S,Se)4 Solar Cells. AB - Kesterite Cu2 ZnSn(S,Se)4 (CZTSSe) is obtained using a facile precursor-solution method followed by selenization. Power-conversion efficiency of 6.0 % is achieved and further improved to 8.2 % after doping the absorber with 0.5 mol % Sb. XRD and Raman spectroscopy show similar characteristics for the undoped and doped CZTSSe. Increasing the Sb concentration increases the grain size and lowers the series resistance. However, further Sb doping beyond 0.5 mol % degrades device performance due to lower open-circuit voltage (and therefore lower fill factor). The effect of Sb doping and the doping concentration are investigated by power dependent and temperature-dependent photoluminescence studies, revealing that trap density is significant reduced with 0.5 mol % Sb doping. Additional doping beyond 0.5 mol % creates more defects that quench the photoexcited carriers and decrease the open-circuit voltage. PMID- 26376604 TI - Correction to Synergistic Anticancer Activity of Fluorescent Copper Nanoclusters and Cisplatin Delivered through a Hydrogel Nanocarrier. PMID- 26376603 TI - Effect of helicopter transport on neurological outcomes in a mouse model of embolic stroke with reperfusion: AIR-MICE pilot study. AB - BACKGROUND: Patients often suffer a stroke at a significant distance from a center capable of delivering endovascular therapy, thus requiring rapid transport by helicopter emergency medical services while receiving a recombinant tissue plasminogen activator infusion that was initiated locally. But little is known about how a helicopter flight may impact the safety and efficacy of recombinant tissue plasminogen activator-induced reperfusion and patient outcomes. AIM: To establish a new animal method to address with fidelity the safety and overall effect of helicopter emergency medical services during thrombolysis. METHODS: Prospective randomized open blinded end-point study of an actual helicopter flight exposure. Adult C57BL/6 male mice were treated with a 10 mg/kg recombinant tissue plasminogen activator infusion two-hours after an embolic middle cerebral artery occlusion. Mice were randomized in pairs to simultaneously receive the infusion during a local helicopter flight or in a ground hangar. RESULTS: Eighteen mice (nine pairs) were analyzed. The paired t-test analysis showed nonsignificant smaller infarction volumes in the helicopter-assigned animals (mean pair difference 33 mm(3) , P = 0.33). The amount of hemorrhagic transformation between the helicopter and ground groups was 4.08 vs. 4.56 MUl, respectively (paired t-test, P = 0.45). CONCLUSIONS: This study shows that helicopter emergency medical services do not have an inherent adverse effect on outcome in a mouse model of ischemic stroke with reperfusion. These results endorse the safety of the practice of using helicopter emergency medical services in stroke patients. The observed potential synergistic effect of helicopter induced factors, such as vibration and changes in altitude, with reperfusion merits further exploration in animal experimental models and in stroke patients. PMID- 26376605 TI - Tunability of exchange bias in Ni@NiO core-shell nanoparticles obtained by sequential layer deposition. AB - Films of magnetic Ni@NiO core-shell nanoparticles (NPs, core diameter d ? 12 nm, nominal shell thickness variable between 0 and 6.5 nm) obtained with sequential layer deposition were investigated, to gain insight into the relationships between shell thickness/morphology, core-shell interface, and magnetic properties. Different values of NiO shell thickness t(s) could be obtained while keeping the Ni core size fixed, at variance with conventional oxidation procedures where the oxide shell is grown at the expense of the core. Chemical composition, morphology of the as-produced samples and structural features of the Ni/NiO interface were investigated with x-ray photoelectron spectroscopy and microscopy (scanning electron microscopy, transmission electron microscopy) techniques, and related with results from magnetic measurements obtained with a superconducting quantum interference device. The effect of the shell thickness on the magnetic properties could be studied. The exchange bias (EB) field H(bias) is small and almost constant for ts up to 1.6 nm; then it rapidly grows, with no sign of saturation. This behavior is clearly related to the morphology of the top NiO layer, and is mostly due to the thickness dependence of the NiO anisotropy constant. The ability to tune the EB effect by varying the thickness of the last NiO layer represents a step towards the rational design and synthesis of core shell NPs with desired magnetic properties. PMID- 26376606 TI - Update on Peritoneal Dialysis: Core Curriculum 2016. PMID- 26376607 TI - Unhealthy Glasgow: a case for ecological public health? AB - Ecological public health has been proposed as an approach appropriate for addressing the multiple transitions that currently affect human health and sustainability. The paper draws on the author's experience in public health in Glasgow to analyse the health challenges faced by this postindustrial Scottish city. Like other such cities, it not only faces multiple health challenges but also demonstrates a currently unexplained excess mortality that has been dubbed the 'Glasgow Effect'. To explore this troubled mixture, the paper outlines four historical waves of public health challenge and response in Glasgow over the last century, and proposes that a fifth is emerging. The challenge now is how to negotiate environmental sustainability with social, political and economic sustainability to enhance health for all. The paper suggests that gains made by past approaches still need to be protected and can be included within ecological public health, but they lack the wider vision, coherence and capacity required if cities are to address the scale and range of contemporary conditions. A number of lessons are offered for the ecological public health perspective. PMID- 26376608 TI - Ehlers Danlos syndrome and gastrointestinal manifestations: a 20-year experience at Mayo Clinic. AB - BACKGROUND: Gastrointestinal (GI) manifestations are found in Ehlers Danlos syndrome (EDS) hypermobility subtype (HM). We aimed to assess associations between EDS HM and other EDS subtypes with GI manifestations. METHODS: We reviewed medical records of EDS patients evaluated at Mayo Clinic's Medical Genetics Clinic 1994-2013. We extracted information regarding EDS subtypes, GI manifestations, and treatments. KEY RESULTS: We identified 687 patients; 378 (56%) had associated GI manifestations (female 86.8%, diagnosis mean age 29.6 years). Of the patients identified, 58.9% (43/73) had EDS classic, 57.5% (271/471) EDS HM, 47.3% (27/57) EDS vascular subtypes. In addition, 86 patients had EDS that could not be classified in any of those three subtypes. Commonest GI symptoms were: abdominal pain (56.1%), nausea (42.3%), constipation (38.6%), heartburn (37.6%), and irritable bowel syndrome-like symptoms (27.5%). Many GI symptoms were commoner in EDS HM than the other subtypes together. Among 37.8% of the 378 patients who underwent esophagogastroduodenoscopy, the commonest abnormalities were gastritis, hiatal hernia and reflux esophagitis. Abnormal gastric emptying was observed in 22.3% (17/76): 11.8% delayed and 10.5% accelerated. Colonic transit was abnormal in 28.3% (13/46): 19.6% delayed and 8.7% accelerated. Rectal evacuation disorder was confirmed in 18/30 patients who underwent anorectal manometry. Angiography showed aneurysms in abdominal vessels in EDS vascular type. Proton pump inhibitors (38%) and drugs for constipation (23%) were the most commonly used medications. A minority underwent colectomy (2.9%) or small bowel surgery (4%). CONCLUSIONS & INFERENCES: EDS HM and other subtypes should be considered in patients with chronic functional GI symptoms and abdominal vascular lesions. PMID- 26376609 TI - Unprecedented side reactions in Stille coupling: desired ones for Stille polycondensation. AB - Two types of unprecedented side reactions were identified in the Stille coupling reaction, including the direct C-H stannylation of the alpha-hydrogen of thiophene and the stannylation of arylbromides with trialkylstannane bromide. These results reveal the major source of enhancements for Stille polycondensation efficiency. PMID- 26376610 TI - Trap-shyness subsidence is a threshold function of mark-recapture interval in brown mudfish Neochanna apoda populations. AB - The influence of capture interval on trap shyness, and temperature, rainfall and drought on capture probability (p) in 827 brown mudfish Neochanna apoda was quantified using mark-recapture models. In particular, it was hypothesized that the loss of trapping memory in marked N. apoda would lead to a capture-interval threshold required to minimize trap shyness. Neochanna apoda trap shyness approximated a threshold response to capture interval, declining rapidly with increasing capture intervals up to 16.5 days, after which p remained constant. Tests for detecting trap-dependent capture probability in Cormack-Jolly-Seber models failed to detect trap shyness in N. apoda capture histories with capture intervals averaging 16 days. This confirmed the applicability of the 16 day capture-interval threshold for mark-recapture studies. Instead, N. apoda p was positively influenced by water temperature and rainfall during capture. These results imply that a threshold capture interval is required to minimize the trade off between the competing assumptions of population closure and p homogeneity between capture occasions in closed mark-recapture models. Moreover, environmental factors that influence behaviour could potentially confound abundance indices, and consequently abundance trends should be interpreted with caution in the face of long-term climate change, such as with global warming. PMID- 26376611 TI - Ethanol-assisted gel chromatography for single-chirality separation of carbon nanotubes. AB - Surfactants or polymers are usually used for the liquid processing of carbon nanotubes for their structure separation. However, they are difficult to remove after separation, affecting the intrinsic properties and applications of the separated species. Here, we report an ethanol-assisted gel chromatography for the chirality separation of single-walled carbon nanotubes (SWCNTs), in which ethanol is employed to finely tune the density/coverage of sodium dodecyl sulfate (SDS) on nanotubes, and thus the interactions between SWCNTs and an allyl dextran-based gel. Incrementally increasing the ethanol content in a low-concentration SDS eluent leads to successive desorption of the different structure SWCNTs adsorbed on the gel, and to achieve multiple distinct (n, m) single-chirality species. The use of ethanol enables the working concentration of SDS to be reduced dramatically and also avoids the introduction of other surfactants or chemical reagents. More importantly, ethanol can be easily removed after separation. The ability of ethanol to tune the interactions between SWCNTs and the gel also gives a deeper insight into the separation mechanism of SWCNTs using gel chromatography. PMID- 26376612 TI - EPHA4 is overexpressed but not functionally active in Sezary syndrome. AB - EPHA4 belongs to the largest subfamily of receptor tyrosine kinases. In addition to its function during development, overexpression of EPHA4 in tumors has been correlated with increased proliferation, migration and poor survival. Several genome-wide transcription profiling studies have demonstrated high EPHA4 expression in Sezary syndrome (SS), a leukemic variant of cutaneous CD4+ T-cell lymphoma (CTCL) with an aggressive clinical course and poor prognosis. In this study we set out to explore the functional role of EPHA4 in SS. Both high EPHA4 mRNA and protein expression was found in circulating SS-cells of patients compared to healthy CD4+ T-cells. However, using a phosphospecific EPHA4 antibody, phosphorylation of the EPHA4 kinase domain was not detected in either circulating or skin residing SS cells. Moreover, treatment with the phosphatase inhibitor pervanadate did not result in detectable phosphorylation of the EPHA4 kinase domain, in either SS cells or in healthy CD4+ T-cells. Thus, the results from our study confirm high EPHA4 expression in SS cells both on the mRNA and protein levels, making EPHA4 a good diagnostic marker. However, the overexpressed EPHA4 does not appear to be functionally active and its overexpression might be secondary to other oncogenic drivers in SS, like STAT3 and TWIST1. PMID- 26376613 TI - Leptin signalling, obesity and prostate cancer: molecular and clinical perspective on the old dilemma. AB - The prevalence of global obesity is increasing. Obesity is associated with general cancer-related morbidity and mortality and is a known risk factor for development of specific cancers. A recent large systematic review of 24 studies based on meta-analysis of 11,149 patients with prostate cancer showed a significant correlation between obesity and the risk of advanced prostate cancer. Further, a sustained reduction in BMI correlates with a decreased risk of developing aggressive disease. On the other hand, the correlation between consuming different products and prostate cancer occurrence/risk is limited.Here, we review the role of adipose tissue from an endocrine perspective and outline the effect of adipokines on cancer metabolism, with particular focus on leptin. Leptin exerts its physiological and pathological effects through modification of intracellular signalling, most notably activating the Janus kinase (JAK) 2/signal transducer and activator of transcription (STAT) 3 pathway and recently shown sphingolipid pathway. Both high levels of leptin in circulation and leptin receptor mutation are associated with prostate cancer risk in human patients; however, the in vivo mechanistic evidence is less conclusive.Given the complexity of metabolic cancer pathways, it is possible that leptin may have varying effects on prostate cancer at different stages of its development, a point that may be addressed by further epidemiological studies. PMID- 26376614 TI - Functional osteoclastogenesis: the baseline variability in blood donor precursors is not associated with age and gender. AB - Mononuclear osteoclast precursors circulate in the monocyte fraction of peripheral blood and form multinuclear cells with all osteoclastic phenotypic characteristics when cultured in the presence of macrophage colony stimulating factor (M-CSF) and receptor activator of nuclear factor kB ligand (RANKL). The method to obtain osteoclast precursors from peripheral blood is simple but the number of recovered osteoclasts is often largely insufficient for functional analyses. The original aim of this study was to develop a rapid and efficient method that could overcome the donor variability and enrich the osteoclast precursors from a small volume of peripheral blood as a basis for future clinical studies to correlate the differentiation potential of circulating osteoclast precursors with bone lesions in cancer patients. We improved the efficiency of osteoclastogenesis by reducing isolation and purification times and overcame the use of flow cytometry and immunomagnetic purification procedures. In our culture system the osteoclast number was increased several-fold and the precursors were able to reach a full differentiation within seven days of culture. Both age as well as gender differences in osteoclastogenesis efficiency were no longer evident by processing limited volume blood samples with this simple and rapid method. PMID- 26376617 TI - Substrate-Controlled Asymmetric Total Syntheses of Microcladallenes A, B, and C Based on the Proposed Structures. AB - Substrate-controlled asymmetric total syntheses of (+)-microcladallenes A, B, and C have been accomplished based on the proposed structures. The syntheses of microcladallenes A and B confirmed the structures and absolute configurations of both natural products. However, the synthesis of microcladallene C, which includes seven stereogenic centers and an (R)-bromoallene in its compact C15 framework, brought the realization that its proposed structure must be revised. The introduction of C12-bromine into these natural products with retention of configuration relied on TiBr4 -mediated nucleophile-assisting leaving group brominations, the stereochemical outcome of which could be attributed, at least in part, to an oxonium or halonium ion formation-fragmentation sequence through intricate neighboring group participation. In addition, the pivotal beta-oriented vicinal cis-dichloride function in microcladallene C was elaborated through a novel tandem Cl2 -induced electrophilic cyclization/imidate chlorination process. The positive rotations of these natural products with an (R)-bromoallene constitute exceptions to Lowe's rule for reasons yet to be determined. PMID- 26376615 TI - Targeting Batf2 for infectious diseases and cancer. AB - The family members Batf, Batf2 and Batf3 belong to a class of transcription factors containing basic leucine zipper domains that regulate various immunological functions and control the development and differentiation of immune cells. Functional studies by others demonstrated a predominant role for Batf in controlling Th2 cell functions and lineage development of T lymphocytes as well as a critical role of Batf, Batf2 and Batf3 in CD8alpha+dendritic cell development. Moreover, Batf family member expression was measured in a vast collection of mouse and human cell types by cap analysis gene expression (CAGE), a recent developed sequencing technology, showing reasonable expression spectrum in immune cells consistent with previously published expression profiles. Batf and Batf3 were highly expressed in lymphocytes and the earlier moderately expressed in myeloid lineages. Batf2 was predominantly expressed in monocytes/macrophages. Functional studies in mice demonstrated that Batf2 has a central role in macrophage activation by regulating inflammatory responses during lipopolysaccharides stimulation and mycobacterial infection. Hence, Batf2 could be used as a biomarker and a potential host directed drug target in tuberculosis. Moreover, Batf2 act as a tumor suppressor gene and augmenting Batf2 in malignant cells might be an encouraging therapeutic treatment against cancer. PMID- 26376616 TI - Phosphorylation and inactivation of PTEN at residues Ser380/Thr382/383 induced by Helicobacter pylori promotes gastric epithelial cell survival through PI3K/Akt pathway. AB - Phosphorylation of PTEN at residues Ser380/Thr382/383 leads to loss of phosphatase activity and tumor suppressor function. Here, we found that phosphorylation of PTEN at residues Ser380/Thr382/383 was increased with gastric carcinogenesis, and more importantly, Helicobacter pylori was a trigger of this modification in chronic non-atrophic gastritis. H. pylori could phosphorylate and inactivate PTEN in vivo and in vitro, resulting in survival of gastric epithelial cells. Furthermore, stable expression of dominant-negative mutant PTEN or inhibition of Akt prevented the enhanced survival induced by H. pylori. These results indicate that PTEN phosphorylation at residues Ser380/Thr382/383 is a novel mechanism of PTEN inactivation in gastric carcinogenesis, and H. pylori triggers this modification, resulting in activation of the PI3K/Akt pathway and promotion of cell survival. PMID- 26376618 TI - Comparison of responses of salivary antioxidant markers to exhaustive aerobic exercise in smoker and non-smoker young girls. AB - BACKGROUND: Smoking is known as a serious global public health problem, and is also an important risk factor for oral diseases and cause of oxidative stress and cellular damage. Saliva is the first biological medium encountered during inhalation of cigarette smoke. Additionally, previous studies demonstrated that exhaustive aerobic exercise could increase oxidative stress and cellular damage. Therefore, the main aim of this study was to compare the response of salivary antioxidants (peroxides (POX), uric acid (UA), 1-1dipheny l-2-picrylhydrazyl hydrate (DPPH) of exhaustive aerobic exercise between healthy smoker and non smoker young girls. METHODS: Ten smokers and 10 non-smokers were enrolled for this study. Subjects performed a progressive cycle ergometer with an initial load of 50 W that was increased 50Wevery 3 minutes at the speed of 60rpm, until exhaustion. Un-stimulated saliva samples were collected before, immediately and 1 hour after exercise. RESULTS: The results showed that POX activity and UA concentration significantly increased immediately after exercise in both groups when compared to the pre exercise values (P<0.01). The level of salivary POX of non-smokers were greater than smokers immediately after exercise (P<0.01). Aerobic exercise caused a decrease in salivary DPPH activity immediately and 1 h after exercise in both groups (P<0.01). When the DPPH values were compared between smoker and non-smoker subjects, a significant decrease was observed in smokers immediately and 1 h after exercise (P<0.01). CONCLUSIONS: In conclusion, aerobic exercise was induced oxidative stress in both groups but oxidative stress in smoking females was greater. PMID- 26376620 TI - The Fe-V Cofactor of Vanadium Nitrogenase Contains an Interstitial Carbon Atom. AB - The first direct evidence is provided for the presence of an interstitial carbide in the Fe-V cofactor of Azotobacter vinelandii vanadium nitrogenase. As for our identification of the central carbide in the Fe-Mo cofactor, we employed Fe Kbeta valence-to-core X-ray emission spectroscopy and density functional theory calculations, and herein report the highly similar spectra of both variants of the cofactor-containing protein. The identification of an analogous carbide, and thus an atomically homologous active site in vanadium nitrogenase, highlights the importance and influence of both the interstitial carbide and the identity of the heteroatom on the electronic structure and catalytic activity of the enzyme. PMID- 26376619 TI - Sugar consumption, metabolic disease and obesity: The state of the controversy. AB - The impact of sugar consumption on health continues to be a controversial topic. The objective of this review is to discuss the evidence and lack of evidence that allows the controversy to continue, and why resolution of the controversy is important. There are plausible mechanisms and research evidence that supports the suggestion that consumption of excess sugar promotes the development of cardiovascular disease (CVD) and type 2 diabetes (T2DM) both directly and indirectly. The direct pathway involves the unregulated hepatic uptake and metabolism of fructose, leading to liver lipid accumulation, dyslipidemia, decreased insulin sensitivity and increased uric acid levels. The epidemiological data suggest that these direct effects of fructose are pertinent to the consumption of the fructose-containing sugars, sucrose and high fructose corn syrup (HFCS), which are the predominant added sugars. Consumption of added sugar is associated with development and/or prevalence of fatty liver, dyslipidemia, insulin resistance, hyperuricemia, CVD and T2DM, often independent of body weight gain or total energy intake. There are diet intervention studies in which human subjects exhibited increased circulating lipids and decreased insulin sensitivity when consuming high sugar compared with control diets. Most recently, our group has reported that supplementing the ad libitum diets of young adults with beverages containing 0%, 10%, 17.5% or 25% of daily energy requirement (Ereq) as HFCS increased lipid/lipoprotein risk factors for CVD and uric acid in a dose response manner. However, un-confounded studies conducted in healthy humans under a controlled, energy-balanced diet protocol that enables determination of the effects of sugar with diets that do not allow for body weight gain are lacking. Furthermore, recent reports conclude that there are no adverse effects of consuming beverages containing up to 30% Ereq sucrose or HFCS, and the conclusions from several meta-analyses suggest that fructose has no specific adverse effects relative to any other carbohydrate. Consumption of excess sugar may also promote the development of CVD and T2DM indirectly by causing increased body weight and fat gain, but this is also a topic of controversy. Mechanistically, it is plausible that fructose consumption causes increased energy intake and reduced energy expenditure due to its failure to stimulate leptin production. Functional magnetic resonance imaging (fMRI) of the brain demonstrates that the brain responds differently to fructose or fructose containing sugars compared with glucose or aspartame. Some epidemiological studies show that sugar consumption is associated with body weight gain, and there are intervention studies in which consumption of ad libitum high-sugar diets promoted increased body weight gain compared with consumption of ad libitum low- sugar diets. However, there are no studies in which energy intake and weight gain were compared in subjects consuming high or low sugar, blinded, ad libitum diets formulated to ensure both groups consumed a comparable macronutrient distribution and the same amounts of fiber. There is also little data to determine whether the form in which added sugar is consumed, as beverage or as solid food, affects its potential to promote weight gain. It will be very challenging to obtain the funding to conduct the clinical diet studies needed to address these evidence gaps, especially at the levels of added sugar that are commonly consumed. Yet, filling these evidence gaps may be necessary for supporting the policy changes that will help to turn the food environment into one that does not promote the development of obesity and metabolic disease. PMID- 26376623 TI - Medication prescribing errors in the medical intensive care unit of Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia. AB - BACKGROUND: Medication errors (MEs) are important problems in all hospitalized populations, especially in intensive care unit (ICU). Little is known about the prevalence of medication prescribing errors in the ICU of hospitals in Ethiopia. The aim of this study was to assess medication prescribing errors in the ICU of Tikur Anbessa Specialized Hospital using retrospective cross-sectional analysis of patient cards and medication charts. RESULTS: About 220 patient charts were reviewed with a total of 1311 patient-days, and 882 prescription episodes. 359 MEs were detected; with prevalence of 40 per 100 orders. Common prescribing errors were omission errors 154 (42.89%), 101 (28.13%) wrong combination, 48 (13.37%) wrong abbreviation, 30 (8.36%) wrong dose, wrong frequency 18 (5.01%) and wrong indications 8 (2.23%). CONCLUSIONS: The present study shows that medication errors are common in medical ICU of Tikur Anbessa Specialized Hospital. These results suggest future targets of prevention strategies to reduce the rate of medication error. PMID- 26376622 TI - A Quasi-Experimental Study Analyzing the Effectiveness of Portable High Efficiency Particulate Absorption Filters in Preventing Infections in Hematology Patients during Construction. AB - OBJECTIVE: The increased risk of infection for patients caused by construction and renovation near hematology inpatient clinics is a major concern. The use of high-efficiency particulate absorption (HEPA) filters can reduce the risk of infection. However, there is no standard protocol indicating the use of HEPA filters for patients with hematological malignancies, except for those who have undergone allogeneic hematopoietic stem cell transplantation. This quasi experimental study was designed to measure the efficacy of HEPA filters in preventing infections during construction. MATERIALS AND METHODS: Portable HEPA filters were placed in the rooms of patients undergoing treatment for hematological malignancies because of large-scale construction taking place near the hematology clinic. The rates of infection during the 6 months before and after the installation of the portable HEPA filters were compared. A total of 413 patients were treated during this 1-year period. RESULTS: There were no significant differences in the antifungal prophylaxis and treatment regimens between the groups. The rates of infections, clinically documented infections, and invasive fungal infections decreased in all of the patients following the installation of the HEPA filters. When analyzed separately, the rates of invasive fungal infections were similar before and after the installation of HEPA filters in patients who had no neutropenia or long neutropenia duration. HEPA filters were significantly protective against infection when installed in the rooms of patients with acute lymphocytic leukemia, patients who were undergoing consolidation treatment, and patients who were neutropenic for 1-14 days. CONCLUSION: Despite the advent of construction and the summer season, during which environmental Aspergillus contamination is more prevalent, no patient or patient subgroup experienced an increase in fungal infections following the installation of HEPA filters. The protective effect of HEPA filters against infection was more pronounced in patients with acute lymphocytic leukemia, patients undergoing consolidation therapy, and patients with moderate neutropenia. PMID- 26376624 TI - De novo mutations in ARID1B associated with both syndromic and non-syndromic short stature. AB - BACKGROUND: Human height is a complex trait with a strong genetic basis. Recently, a significant association between rare copy number variations (CNVs) and short stature has been identified, and candidate genes in these rare CNVs are being explored. This study aims to evaluate the association between mutations in ARID1B gene and short stature, both the syndromic and non-syndromic form. RESULTS: Based on a case-control study of whole genome chromosome microarray analysis (CMA), three overlapping CNVs were identified in patients with developmental disorders who exhibited short stature. ARID1B, a causal gene for Coffin Siris syndrome, is the only gene encompassed by all three CNVs. A following retrospective genotype-phenotype analysis based on a literature review confirmed that short stature is a frequent feature in those Coffin-Siris syndrome patients with ARID1B mutations. Mutation screening of ARID1B coding regions was further conducted in a cohort of 48 non-syndromic short stature patients,andfour novel missense variants including two de novo mutations were found. CONCLUSION: These results suggest that haploinsufficient mutations of ARID1B are associated with syndromic short stature including Coffin-Siris syndrome and intellectual disability, while rare missense variants in ARID1B are associated with non syndromic short stature. This study supports the notion that mutations in genes related to syndromic short stature may exert milder effect and contribute to short stature in the general population. PMID- 26376625 TI - Functional characterization of DnSIZ1, a SIZ/PIAS-type SUMO E3 ligase from Dendrobium. AB - BACKGROUND: SUMOylation is an important post-translational modification of eukaryotic proteins that involves the reversible conjugation of a small ubiquitin related modifier (SUMO) polypeptide to its specific protein substrates, thereby regulating numerous complex cellular processes. The PIAS (protein inhibitor of activated signal transducers and activators of transcription [STAT]) and SIZ (scaffold attachment factor A/B/acinus/PIAS [SAP] and MIZ) proteins are SUMO E3 ligases that modulate SUMO conjugation. The characteristic features and SUMOylation mechanisms of SIZ1 protein in monocotyledon are poorly understood. Here, we examined the functions of a homolog of Arabidopsis SIZ1, a functional SIZ/PIAS-type SUMO E3 ligase from Dendrobium. RESULTS: In Dendrobium, the predicted DnSIZ1 protein has domains that are highly conserved among SIZ/PIAS type proteins. DnSIZ1 is widely expressed in Dendrobium organs and has a up regulated trend by treatment with cold, high temperature and wounding. The DnSIZ1 protein localizes to the nucleus and shows SUMO E3 ligase activity when expressed in an Escherichia coli reconstitution system. Moreover, ectopic expression of DnSIZ1 in the Arabidopsis siz1-2 mutant partially complements several phenotypes and results in enhanced levels of SUMO conjugates in plants exposed to heat shock conditions. We observed that DnSIZ1 acts as a negative regulator of flowering transition which may be via a vernalization-induced pathway. In addition, ABA hypersensitivity of siz1-2 seed germination can be partially suppressed by DnSIZ1. CONCLUSIONS: Our results suggest that DnSIZ1 is a functional homolog of the Arabidopsis SIZ1 with SUMO E3 ligase activity and may play an important role in the regulation of Dendrobium stress responses, flowering and development. PMID- 26376626 TI - An introduction to implementation science for the non-specialist. AB - BACKGROUND: The movement of evidence-based practices (EBPs) into routine clinical usage is not spontaneous, but requires focused efforts. The field of implementation science has developed to facilitate the spread of EBPs, including both psychosocial and medical interventions for mental and physical health concerns. DISCUSSION: The authors aim to introduce implementation science principles to non-specialist investigators, administrators, and policymakers seeking to become familiar with this emerging field. This introduction is based on published literature and the authors' experience as researchers in the field, as well as extensive service as implementation science grant reviewers. Implementation science is "the scientific study of methods to promote the systematic uptake of research findings and other EBPs into routine practice, and, hence, to improve the quality and effectiveness of health services." Implementation science is distinct from, but shares characteristics with, both quality improvement and dissemination methods. Implementation studies can be either assess naturalistic variability or measure change in response to planned intervention. Implementation studies typically employ mixed quantitative qualitative designs, identifying factors that impact uptake across multiple levels, including patient, provider, clinic, facility, organization, and often the broader community and policy environment. Accordingly, implementation science requires a solid grounding in theory and the involvement of trans-disciplinary research teams. The business case for implementation science is clear: As healthcare systems work under increasingly dynamic and resource-constrained conditions, evidence-based strategies are essential in order to ensure that research investments maximize healthcare value and improve public health. Implementation science plays a critical role in supporting these efforts. PMID- 26376627 TI - Association between gross motor function and postural control in sitting in children with Cerebral Palsy: a correlational study in Spain. AB - BACKGROUND: Cerebral palsy (CP) is one of the causes of physical disability in children. Sitting abilities can be described using the Level of Sitting Scale (LSS) and the Gross Motor Function Classification System (GMFCS). There is growing interest in the sitting posture of children with CP owing to a stable sitting position allows for the development of eye-hand coordination, functions of the upper extremities and functional skills. Besides, in recent years researchers have tried to develop a new terminology to classify the CP as performed by the Surveillance of Cerebral Palsy in Europe (SCPE), in order to improve the monitoring of the frequency of the PC, providing a framework for research and service planning. The aim of this study was to analyse the relationship between GMFCS and LSS. The second purpose was to describe how the SCPE relates to sitting abilities with the GMFCS and LSS. METHODS: The study involved 139 children with CP (range 3-18 years) from 24 educational centres. Age, gender, CP classification according to SCPE, GMFCS and LSS levels were recorded by an experienced physiotherapist. RESULTS: A significant inverse relationship between GMFCS and LSS score levels was found (rs = -0.86, p = 0.00). 45.3% of the children capable of leaning in any direction and of re-erecting the trunk (level VIII on the LSS) could walk without limitation (level I on the GMFCS). There were differences in the distribution of the GMFCS (chi(2)(4):50.78) and LSS (chi(2)(7): 37.15) levels and CP according to the distribution of the spasticity (p < 0.01). CONCLUSIONS: There was a negative correlation between both scales and a relation between sitting ability and the capacity to walk with or without technical devices. GMFCS and the LSS are useful tools for describing the functional abilities and limitations of children with CP, specially sitting and mobility. Classification based on the distribution of spasticity and the gross motor function provides clinical information on the prognosis and development of children with CP. PMID- 26376628 TI - Does the presence and mix of destinations influence walking and physical activity? AB - BACKGROUND: Local destinations have previously been shown to be associated with higher levels of both physical activity and walking, but little is known about how specific destinations are related to activity. This study examined associations between types and mix of destinations and both walking frequency and physical activity. METHOD: The sample consisted of 2349 residents of 50 urban areas in metropolitan Melbourne, Australia. Using geographic information systems, seven types of destinations were examined within three network buffers (400 meters (m), 800 m and 1200 m) of respondents' homes. Multilevel logistic regression was used to estimate effects of each destination type separately, as well as destination mix (variety) on: 1) likelihood of walking for at least 10 min >= 4/week; 2) likelihood of being sufficiently physically active. All models were adjusted for potential confounders. RESULTS: All destination types were positively associated with walking frequency, and physical activity sufficiency at 1200 m. For the 800 m buffer: all destinations except transport stops and sports facilities were significantly associated with physical activity, while all except sports facilities were associated with walking frequency; at 400 m, cafe/takeaway food stores and transport stops were associated with walking frequency and physical activity sufficiency, and sports facilities were also associated with walking frequency. Strongest associations for both outcomes were observed for community resources and small food stores at both 800 m and 1200 m. For all buffer distances: greater mix was associated with greater walking frequency. Inclusion of walking in physical activity models led to attenuation of associations. CONCLUSIONS: The results of this analysis indicate that there is an association between destinations and both walking frequency and physical activity sufficiency, and that this relationship varies by destination type. It is also clear that greater mix of destinations positively predicts walking frequency and physical activity sufficiency. PMID- 26376631 TI - The current status of clinics providing private practice cell therapy in Japan. AB - AIM: To clarify the current state of clinics in Japan that offer unproven cell therapies. METHODS: Google searches were performed to collect and analyze what kind of clinics provide what kind of cell therapies. RESULTS: A total of 74 clinics and 247 cases of cell therapies were identified. Various cell therapies, including allograft, were provided not only to seriously ill patients but also to patients with other therapeutic options and healthy individuals. DISCUSSION: Although the practices revealed by our study seem to deviate from international standard, some of these can be construed as legal under the Japanese new act established in 2014. CONCLUSION: Considering many patients travel to foreign countries to seek therapy, more research from non-English-speaking countries is needed. PMID- 26376630 TI - Exploring causal networks underlying fat deposition and muscularity in pigs through the integration of phenotypic, genotypic and transcriptomic data. AB - BACKGROUND: Joint modeling and analysis of phenotypic, genotypic and transcriptomic data have the potential to uncover the genetic control of gene activity and phenotypic variation, as well as shed light on the manner and extent of connectedness among these variables. Current studies mainly report associations, i.e. undirected connections among variables without causal interpretation. Knowledge regarding causal relationships among genes and phenotypes can be used to predict the behavior of complex systems, as well as to optimize management practices and selection strategies. Here, we performed a multistep procedure for inferring causal networks underlying carcass fat deposition and muscularity in pigs using multi-omics data obtained from an F2 Duroc x Pietrain resource pig population. RESULTS: We initially explored marginal associations between genotypes and phenotypic and expression traits through whole genome scans, and then, in genomic regions with multiple significant hits, we assessed gene-phenotype network reconstruction using causal structural learning algorithms. One genomic region on SSC6 showed significant associations with three relevant phenotypes, off-midline10th-rib backfat thickness, loin muscle weight, and average intramuscular fat percentage, and also with the expression of seven genes, including ZNF24, SSX2IP, and AKR7A2. The inferred network indicated that the genotype affects the three phenotypes mainly through the expression of several genes. Among the phenotypes, fat deposition traits negatively affected loin muscle weight. CONCLUSIONS: Our findings shed light on the antagonist relationship between carcass fat deposition and lean meat content in pigs. In addition, the procedure described in this study has the potential to unravel gene phenotype networks underlying complex phenotypes. PMID- 26376629 TI - NT-020 treatment reduces inflammation and augments Nrf-2 and Wnt signaling in aged rats. AB - BACKGROUND: Aging is associated with a decline in stem cell proliferation that is thought to be a result of dysregulated signaling in the neurogenic niche. This results in a diminished and less efficient pool of progenitors. The Wnt pathway plays a key role in the proliferation and differentiation of progenitor cells. Recent publications suggest that the age-related decline in the function of Wnt is a contributor to age-dependent decline in neural progenitors. Similarly, the aged neurogenic niche is characterized by higher levels of inflammatory cytokines. This increased inflammation contributes to the declining function of neural progenitor cells. NT-020, a proprietary blend of polyphenols, has been shown to increase proliferation of neural progenitors and improve cognitive function in aged rats. PURPOSE AND METHODS: In this study, we examined the neurogenic niche in the subgranular zone of the dentate gyrus (SGZ) and the subventricular zone (SVZ) of young and aged rats to determine if dietary supplementation with NT-020 could regulate inflammation and oxidative stress response pathways in neurons, astrocytes, and microglia. Further, we examined NT 020's ability to modulate Wnt signaling in the aged neurogenic niche. To accomplish this, we utilized gene PCR arrays and immunohistochemistry. RESULTS: We observed an increase in nuclear localization of immunopositive labeling of beta-catenin, HO-1, and Nrf2 in all subsets of cell types in both young and aged rats in the SGZ and SVZ following NT-020 treatment. NeuN-positive cells showed a basal increase in nuclear beta-catenin in the aged rats, which was not observed in doublecortin (DCX)-labeled cells, microglia, or astrocytes. Reverse transcription polymerase chain reaction (RT-PCR) analysis of isolated hippocampal tissue revealed that a significant percent of genes involved with inflammation are affected by treatment with NT-020. In addition, several genes that regulate Wnt activity were affected by supplementation. CONCLUSIONS: The results suggest that NT-020 activates oxidative stress response pathways and supports pro neurogenic gene expression in the hippocampus. This may represent the mechanism by which the NT-020 formula enhances performance in learning and memory tasks in aged mice. PMID- 26376632 TI - Are high cumulative doses of erythropoietin neuroprotective in preterm infants? A two year follow-up report. AB - BACKGROUND: Preterm infants are at risk for neurodevelopmental sequelae even in absence of major cerebral lesions. The hypothesis that Human Recombinant Erythropoietin (rEpo) could improve the neurodevelopmental outcome in risk neonates has raised the highest interest in recent years. METHODS: A group of preterm neonates born at a gestational age <= 30 weeks and free from major cerebral lesions or major visual impairment, were included in the study if they had a complete neurologic evaluation for at least 24 months of postmenstrual age. They were assigned to group I in the case they had been treated with rEpo or group II if untreated. The aim was to evaluate whether rEpo, given at the high cumulative doses utilized for hematologic purposes, is able to improve the neurodevelopmental outcome in preterm infants born at a gestational age <= 30 weeks. A group of 104 preterm neonates were studied: 59 neonates who received rEpo for 6.9 +/- 2.4 weeks at a median cumulative dose of 6300 UI/Kg (6337 +/- 2434 UI/Kg), starting at a median age of 4 days and 45 neonates who were born in the period preceding the routine use of rEpo. The neurodevelopmental quotient at 24 month postmenstrual age was assessed utilizing the Griffiths' Mental Developmental Scales. RESULTS: Our results failed to show any difference in the Developmental Quotient at 24 month. Bronchopulmonary dysplasia, minor intraventricular hemorrhages and blood transfusions were the clinical features significantly related to the Developmental Quotient. CONCLUSIONS: Our results do not support the hypothesis that rEpo, administered with the schedule utilized for hematologic purposes, improve the neurodevelopmental outcome of preterm neonates, at least those preterm infants free from major impairments. PMID- 26376633 TI - Nitrative stress, oxidative stress and plasma endothelin levels after inhalation of particulate matter and ozone. AB - BACKGROUND: While exposure to ambient air contaminants is clearly associated with adverse health outcomes, disentangling mechanisms of pollutant interactions remains a challenge. OBJECTIVES: We aimed at characterizing free radical pathways and the endothelinergic system in rats after inhalation of urban particulate matter, ozone, and a combination of particles plus ozone to gain insight into pollutant-specific toxicity mechanisms and any effect modification due to air pollutant mixtures. METHODS: Fischer 344 rats were exposed for 4 h to a 3 * 3 concentration matrix of ozone (0, 0.4, 0.8 ppm) and EHC-93 particles (0, 5, 50 mg/m(3)). Bronchoalveolar lavage fluid (BALF), BAL cells, blood and plasma were analysed for biomarkers of effects immediately and 24 h post-exposure. RESULTS: Inhalation of ozone increased (p < 0.05) lipid oxidation products in BAL cells immediately post-exposure, and increased (p < 0.05) total protein, neutrophils and mature macrophages in the BALF 24 h post-exposure. Ozone increased (p < 0.05) the formation of reactive oxygen species (ROS), assessed by m-, p-, o-tyrosines in BALF (Ozone main effects, p < 0.05), while formation of reactive nitrogen species (RNS), indicated by 3-nitrotyrosine, correlated with dose of urban particles (EHC-93 main effects or EHC-93 * Ozone interactions, p < 0.05). Carboxyhemoglobin levels in blood exhibited particle exposure-related increase (p < 0.05) 24 h post recovery. Plasma 3-nitrotyrosine and o-tyrosine were increased (p < 0.05) after inhalation of particles; the effect on 3-nitrotyrosine was abrogated after exposure to ozone plus particles (EHC-93 * Ozone, p < 0.05). Big endothelin-1 (BET-1) and ET-1 were increased in plasma after inhalation of particles or ozone alone, but the effects appeared to be attenuated by co exposure to contaminants (EHC-93 * Ozone, p < 0.05). Plasma ET levels were positively correlated (p < 0.05) with BALF m- and o-tyrosine levels. CONCLUSIONS: Pollutant-specific changes can be amplified or abrogated following multi pollutant exposures. Oxidative and nitrative stress in the lung compartment may contribute to secondary extra-pulmonary ROS/RNS formation. Nitrative stress and endothelinergic imbalance emerge as potential key pathways of air pollutant health effects, notably of ambient particulate matter. PMID- 26376635 TI - From Bone Marrow Necrosis to Gaucher Disease; A Long Way to Run. PMID- 26376634 TI - Molecular adaptation and salt stress response of Halobacterium salinarum cells revealed by neutron spectroscopy. AB - Halobacterium salinarum is an extreme halophile archaeon with an absolute requirement for a multimolar salt environment. It accumulates molar concentrations of KCl in the cytosol to counterbalance the external osmotic pressure imposed by the molar NaCl. As a consequence, cytosolic proteins are permanently exposed to low water activity and highly ionic conditions. In non adapted systems, such conditions would promote protein aggregation, precipitation, and denaturation. In contrast, in vitro studies showed that proteins from extreme halophilic cells are themselves obligate halophiles. In this paper, adaptation via dynamics to low-salt stress in H. salinarum cells was measured by neutron scattering experiments coupled with microbiological characterization. The molecular dynamic properties of a proteome represent a good indicator for environmental adaptation and the neutron/microbiology approach has been shown to be well tailored to characterize these modifications. In their natural setting, halophilic organisms often have to face important variations in environmental salt concentration. The results showed deleterious effects already occur in the H. salinarum proteome, even when the external salt concentration is still relatively high, suggesting the onset of survival mechanisms quite early when the environmental salt concentration decreases. PMID- 26376636 TI - Prognostic Significance of Uric Acid Levels in Ischemic Stroke Patients. AB - The importance and function of serum uric acid (UA) levels in patients with cardiovascular disease or stroke are unclear. We sought to evaluate the appropriate UA levels for stroke patients and the association between endogenous UA levels and clinical outcomes in acute ischemic stroke (AIS) patients, particularly regarding the possible interaction between gender and UA levels with respect to AIS prognosis. We examined 303 patients who had an onset of ischemic stroke within 48 h. Of those, 101 patients received thrombolytic treatment. Serum UA (MUmol/L) levels were measured the second morning after admission. Patient prognosis was evaluated 90 days after clinical onset by modified Rankin Scale. Patients were divided into four groups according to serum UA quartiles. A binary multivariate logistic regression model was used to assess clinical relevance in regard to functional outcome and endogenous UA levels. Analysis of subgroups by gender and normal glomerular filtration rate were also been done. Poor functional outcome was associated with older age, history of atrial fibrillation, or higher baseline National Institutes of Health Stroke Scale scores. After adjustment for potential confounders, patients with higher UA levels (>380 MUmol/L) or lower UA levels (<=250 MUmol/L) were 2-3 times more likely to have a poor outcome (OR 2.95, 95% CI 1.14-7.61; OR 2.78, 95% CI 1.02-7.58, respectively) compared to the baseline group (UA level 316-380 MUmol/L). The same results were observed in thrombolyzed patients. Patients with high and low UA levels were 9-18 times more likely to having poor outcomes compared to the baseline group (UA level: 316-380 MUmol/L; OR 18.50, 95% CI: 2.041-167.67; OR 9.66, 95% CI 1.42-65.88, respectively). In men, patients with high UA levels were 6 times more likely to have poor outcomes compared to the baseline group (UA level: 279-334 MUmol/L; OR 6.10, 95% CI 1.62-22.93). However, female patients with UA level 271-337 MUmol/L were seven times more likely to perform badly compared to the baseline group (UA level >337 MUmol/L, OR 7.06, 95% CI 1.00-49.81). Serum UA levels in an appropriate range were associated with better outcome in patients with AIS but may be harmful when too high or too low. The association of UA levels with AIS prognosis differed in male and female patients, which highlights the necessity of stratifying by gender in investigations of cerebrovascular risk factors. PMID- 26376638 TI - Socio-economic and cultural vulnerabilities to cervical cancer and challenges faced by patients attending care at Tikur Anbessa Hospital: a cross sectional and qualitative study. AB - BACKGROUND: Cervical cancer is a leading cause of death among women in Ethiopia, affecting them at a time of their life when they are critical to social and economic stability. This study was mainly focused on assessing different socioeconomic and cultural related factors that make women vulnerable to cervical cancer and challenges women face in the process of diagnosis and treatment. METHODS: To achieve the objective of the study both qualitative and quantitative methods were utilized.198 participants were enrolled in a cross- sectional survey and 10 in-depth interviews were conducted with patients in Tikur Anbessa Hospital. A consecutive sampling method was used to select participants in the survey while purposive sampling was employed to select participants in the qualitative design. RESULTS: For the population covered in the study, poverty along with other socio-cultural practices such as early marriage, high parity and to certain extent polygamy were identified as factors that increased the vulnerability of women to cervical cancer. In addition, the study has uncovered several challenges faced by cervical cancer patients in the diagnosis and treatment process. Three types of challenges that include, health care based, psychological and economic were identified. System and practitioner delay were found as the main hurdles within the variable of health care related challenges. What's more, the psychological challenges identified included, fear of recurrence, negative social attitude and distress associated with the side effects from treatments such as fecal & urinary leakage. Furthermore, inability of bearing costs related to treatment and accommodation were cited as the main economic challenges. CONCLUSION: The study showed various socio-economic and cultural vulnerabilities that expose women to cervical cancer and the challenges encountered by cervical cancer patients after their diagnosis. Addressing this issue largely lies in strengthening primary and secondary preventive mechanisms, providing public education about safer sex practices, family planning and eliminating cultural practices such as early marriage and polygamy in connection to cervical cancer. Furthermore, improving the diagnostic and treatment procedures and facilities is also a crucial component that needs due emphasis in the fight against cervical cancer. PMID- 26376639 TI - Falciparum malaria molecular drug resistance in the Democratic Republic of Congo: a systematic review. AB - BACKGROUND: Malaria cases were estimated to 207 million in 2013. One of the problems of malaria control is the emergence and spread of Plasmodium falciparum strains that become resistant to almost all drugs available. Monitoring drug resistance is essential for early detection and subsequent prevention of the spread of drug resistance by timely changes of treatment policy. This review was performed to gather all data available on P. falciparum molecular resistance in DR Congo, as baseline for future assessments. METHODS: The search for this review was undertaken using the electronic databases PubMed and Google Scholar using the terms "malaria", "Congo", "resistance", "molecular", "antimalarial", "efficacy". Articles were classified based on year of collecting, year of publication, sample size and characteristics, molecular markers analysed and polymorphisms detected. RESULTS: Thirteen articles were included and five genes have been analysed in these studies: pfcrt, pfdhps, pfdhfr, pfmdr1 and K13-propeller. The majority of studies included were not representative of the whole country. CONCLUSION: This systematic review demonstrates the lack of molecular resistance studies in DRC. Only 13 studies were identified in almost 15 years. The MOH must implement a national surveillance system for monitoring malaria drug resistance and this surveillance should be conducted frequently and country-representative. PMID- 26376640 TI - A recyclable biotransformation system for L-2-aminobutyric acid production based on immobilized enzyme technology. AB - OBJECTIVE: To make the previously developed biosynthesis of L-2-aminobutyric acid (L-ABA) more suitable for the industrial-scale production. RESULTS: A recyclable biotransformation system was developed based on immobilized enzyme technology. The conversion yield of L-threonine (at 90 g l(-1)) reached 99.9 % and the theoretical yield of L-ABA reached more than 90 % using the optimized biotransformation system by the individual immobilization of threonine deaminase and the co-immobilization of L leucine dehydrogenase and formate dehydrogenase. 90 g L-threonine l(-1) was converted to 73.9 g L-ABA l(-1) >95 % theoretical yield, within 120-145 min in 30 batch transformation experiments. CONCLUSION: The recyclable biotransformation system is promising to fulfill industrial requirements for L-ABA production. PMID- 26376641 TI - An integrated electromechanical-growth heart model for simulating cardiac therapies. AB - An emerging class of models has been developed in recent years to predict cardiac growth and remodeling (G&R). We recently developed a cardiac G&R constitutive model that predicts remodeling in response to elevated hemodynamics loading, and a subsequent reversal of the remodeling process when the loading is reduced. Here, we describe the integration of this G&R model to an existing strongly coupled electromechanical model of the heart. A separation of timescale between growth deformation and elastic deformation was invoked in this integrated electromechanical-growth heart model. To test our model, we applied the G&R scheme to simulate the effects of myocardial infarction in a realistic left ventricular (LV) geometry using the finite element method. We also simulate the effects of a novel therapy that is based on alteration of the infarct mechanical properties. We show that our proposed model is able to predict key features that are consistent with experiments. Specifically, we show that the presence of a non contractile infarct leads to a dilation of the left ventricle that results in a rightward shift of the pressure volume loop. Our model also predicts that G&R is attenuated by a reduction in LV dilation when the infarct stiffness is increased. PMID- 26376642 TI - A novel strain energy relationship for red blood cell membrane skeleton based on spectrin stiffness and its application to micropipette deformation. AB - Red blood cell (RBC) membrane skeleton is a closed two-dimensional elastic network of spectrin tetramers with nodes formed by short actin filaments. Its three-dimensional shape conforms to the shape of the bilayer, to which it is connected through vertical linkages to integral membrane proteins. Numerous methods have been devised over the years to predict the response of the RBC membrane to applied forces and determine the corresponding increase in the skeleton elastic energy arising either directly from continuum descriptions of its deformation, or seeking to relate the macroscopic behavior of the membrane to its molecular constituents. In the current work, we present a novel continuum formulation rooted in the molecular structure of the membrane and apply it to analyze model deformations similar to those that occur during aspiration of RBCs into micropipettes. The microscopic elastic properties of the skeleton are derived by treating spectrin tetramers as simple linear springs. For a given local deformation of the skeleton, we determine the average bond energy and define the corresponding strain energy function and stress-strain relationships. The lateral redistribution of the skeleton is determined variationally to correspond to the minimum of its total energy. The predicted dependence of the length of the aspirated tongue on the aspiration pressure is shown to describe the experimentally observed system behavior in a quantitative manner by taking into account in addition to the skeleton energy an energy of attraction between RBC membrane and the micropipette surface. PMID- 26376643 TI - Incidentalomas during imaging for primary hyperparathyroidism--incidence and clinical outcomes. AB - BACKGROUND: Imaging for pre-operative localisation of parathyroid glands in primary hyperparathyroidism is now routine. This has led to the detection of incidental lesions (incidentalomas) in other organs, the nature of which is not well characterised. The aim of this study was to determine the incidence, characteristics and outcomes in patients who had incidental findings on parathyroid imaging. METHODS: Records of patients who underwent imaging for primary hyperparathyroidism over 2 years were reviewed to identify incidental lesions detected on parathyroid imaging. Patients with persistent or renal hyperparathyroidism were excluded. Details on the management of detected incidentalomas were obtained from patient records. RESULTS: Incidentalomas were identified in 17 of 170 patients (10%) undergoing parathyroid imaging. Incidentalomas included thyroid (n = 11), breast (n = 3), lateral compartment of the neck (n = 1), lung (n = 1) and clavicle (n = 1). However, no disease of clinical significance needing treatment was detected on further investigation. CONCLUSIONS: Although a significant proportion of patients undergoing parathyroid imaging had incidental lesions detected, these seem to be of little clinical significance. The morbidity and cost of further interventions on these incidentalomas need to be weighed against the benefits of routine imaging in improving outcomes of first-time surgery in patients with primary hyperparathyroidism. PMID- 26376644 TI - RNA-seq analysis of Pichia anomala reveals important mechanisms required for survival at low pH. AB - BACKGROUND: The product yield and titers of biological processes involving the conversion of biomass to desirable chemicals can be limited by environmental stresses encountered by the microbial hosts used for the bioconversion. One of these main stresses is growth inhibition due to exposure to low pH conditions. In order to circumvent this problem, understanding the biological mechanisms involved in acid stress response and tolerance is essential. Characterisation of wild yeasts that have a natural ability to resist such harsh conditions will pave the way to understand the biological basis underlying acid stress resistance. Pichia anomala possesses a unique ability to adapt to and tolerate a number of environmental stresses particularly low pH stress giving it the advantage to outcompete other microorganisms under such conditions. However, the genetic basis of this resistance has not been previously studied. RESULTS: To this end, we isolated an acid resistant strain of P. anomala, performed a gross phenotypic characterisation at low pH and also performed a whole genome and total RNA sequencing. By integrating the RNA-seq data with the genome sequencing data, we found that several genes associated with different biological processes including proton efflux, the electron transfer chain and oxidative phosphorylation were highly expressed in P. anomala cells grown in low pH media. We therefore present data supporting the notion that a high expression of proton pumps in the plasma membrane coupled with an increase in mitochondrial ATP production enables the high level of acid stress tolerance of P. anomala. CONCLUSIONS: Our findings provide insight into the molecular and genetic basis of low pH tolerance in P. anomala which was previously unknown. Ultimately, this is a step towards developing non-conventional yeasts such as P. anomala for the production of industrially relevant chemicals under low pH conditions. PMID- 26376645 TI - Thermodynamics of protein-ligand interactions as a reference for computational analysis: how to assess accuracy, reliability and relevance of experimental data. AB - For a conscientious interpretation of thermodynamic parameters (Gibbs free energy, enthalpy and entropy) obtained by isothermal titration calorimetry (ITC), it is necessary to first evaluate the experimental setup and conditions at which the data were measured. The data quality must be assessed and the precision and accuracy of the measured parameters must be estimated. This information provides the basis at which level discussion of the data is appropriate, and allows insight into the significance of comparisons with other data. The aim of this article is to provide the reader with basic understanding of the ITC technique and the experimental practices commonly applied, in order to foster an appreciation for how much measured thermodynamic parameters can deviate from ideal, error-free values. Particular attention is paid to the shape of the recorded isotherm (c-value), the influence of the applied buffer used for the reaction (protonation reactions, pH), the chosen experimental settings (temperature), impurities of protein and ligand, sources of systematic errors (solution concentration, solution activity, and device calibration) and to the applied analysis software. Furthermore, we comment on enthalpy-entropy compensation, heat capacities and van't Hoff enthalpies. PMID- 26376646 TI - Quality control material for the detection of somatic mutations in fixed clinical specimens by next-generation sequencing. AB - BACKGROUND: Targeted next generation sequencing (NGS) technology to assess the mutational status of multiple genes on formalin-fixed, paraffin embedded (FFPE) tumors is rapidly being adopted in clinical settings, where quality control (QC) practices are required. Establishing reliable FFPE QC materials for NGS can be challenging and/or expensive. Here, we established a reliable and cost-effective FFPE QC material for routine utilization in the Ion AmpliSeqTM Cancer Hotspot Panel v2 (CHP2) assay. METHODS: The performance characteristics of the CHP2 assay were determined by sequencing various cell line mixtures and 55 different FFPE tumors on the Ion Torrent PGM platform. A FFPE QC material was prepared from a mixture of cell lines derived from different cancers, comprising single nucleotide variants and small deletions on actionable genes at different allelic frequencies. RESULTS: The CHP2 assay performed with high precision and sensitivity when custom variant calling pipeline parameters where established. In addition, all expected somatic variants in the QC material were consistently called at variant frequencies ranging from 9.1 % (CV = 11.1 %) to 37.9 % (CV = 2.8 %). CONCLUSIONS: The availability of a reliable and cost-effective QC material is instrumental in assessing the performance of this or any targeted NGS assay that detects somatic variants in fixed solid tumor specimens. PMID- 26376647 TI - Clinical Utility of a Plasma Protein Classifier for Indeterminate Lung Nodules. AB - Evaluation of indeterminate pulmonary nodules is a complex challenge. Most are benign but frequently undergo invasive and costly procedures to rule out malignancy. A plasma protein classifier was developed that identifies likely benign nodules that can be triaged to CT surveillance to avoid unnecessary invasive procedures. The clinical utility of this classifier was assessed in a prospective-retrospective analysis of a study enrolling 475 patients with nodules 8-30 mm in diameter who had an invasive procedure to confirm diagnosis at 12 sites. Using this classifier, 32.0 % (CI 19.5-46.7) of surgeries and 31.8 % (CI 20.9-44.4) of invasive procedures (biopsy and/or surgery) on benign nodules could have been avoided. Patients with malignancy triaged to CT surveillance by the classifier would have been 24.0 % (CI 19.2-29.4). This rate is similar to that described in clinical practices (24.5 % CI 16.2-34.4). This study demonstrates the clinical utility of a non-invasive blood test for pulmonary nodules. PMID- 26376648 TI - Analysis of spread and persistence for stream insects with winged adult stages. AB - Species such as stoneflies have complex life history details, with larval stages in the river flow and adult winged stages on or near the river bank. Winged adults often bias their dispersal in the upstream direction, and this bias provides a possible mechanism for population persistence in the face of unidirectional river flow. We use an impulsive reaction-diffusion equation with non-local impulse to describe the population dynamics of a stream-dwelling organism with a winged adult stage, such as stoneflies. We analyze this model from a variety of perspectives so as to understand the effect of upstream dispersal on population persistence. On the infinite domain we use the perspective of weak versus local persistence, and connect the concept of local persistence to positive up and downstream spreading speeds. These spreading speeds, in turn are connected to minimum travelling wave speeds for the linearized operator in upstream and downstream directions. We show that the conditions for weak and local persistence differ, and describe how weak persistence can give rise to a population whose numbers are growing but is being washed out because it cannot maintain a toe hold at any given location. On finite domains, we employ the concept of a critical domain size and dispersal success approximation to determine the ultimate fate of the populations. A simple, explicit formula for a special case allows us to quantify exactly the difference between weak and local persistence. PMID- 26376649 TI - Treatment against human endogenous retrovirus: a possible personalized medicine approach for multiple sclerosis. AB - Human endogenous retroviruses (HERV) represent about 8 % of the human genome. Some of these genetic elements are expressed in pathological circumstances. A HERV protein, the multiple sclerosis-associated retrovirus (MSRV) envelope protein (MSRV-Env), is expressed in the blood and active brain lesions of multiple sclerosis (MS) patients. It possesses pro-inflammatory and myelinotoxic properties. The patterns of expression and pathogenic properties of MSRV-Env make it a relevant drug target for MS therapeutics-in particular for preventing neurodegeneration, a key component of progressive forms of MS. An immunoglobulin G4 monoclonal antibody (mAb), called GNbAC1, has been developed to neutralize this pathogenic target. After showing neutralizing effects in vitro and in mouse models of MS, GNbAC1 is now in phase II clinical development. MSRV-related biomarkers such as MSRV-Env and MSRV polymerase (MSRV-Pol) gene transcripts are overexpressed in the blood and cerebrospinal fluid of patients with MS. These biomarkers may have prognostic value for long-term MS evolution, and their transcription levels in blood decline during treatments with GNbAC1, which has also been reported in patients administered reference MS drugs such as natalizumab or interferon-beta. GNbAC1 as a new MSRV-Env-antagonist mAb could be a specific and causal treatment for MS, with a particular application for progressive forms of the disease. For possible use in companion diagnostic tests, MSRV-associated biomarkers could open the door to a personalized therapeutic approach for MS. PMID- 26376651 TI - Polymerase zeta Activity Is Linked to Replication Timing in Humans: Evidence from Mutational Signatures. AB - Replication timing is an important determinant of germline mutation patterns, with a higher rate of point mutations in late replicating regions. Mechanisms underlying this association remain elusive. One of the suggested explanations is the activity of error-prone DNA polymerases in late-replicating regions. Polymerase zeta (pol zeta), an essential error-prone polymerase biased toward transversions, also has a tendency to produce dinucleotide mutations (DNMs), complex mutational events that simultaneously affect two adjacent nucleotides. Experimental studies have shown that pol zeta is strongly biased toward GC->AA/TT DNMs. Using primate divergence data, we show that the GC->AA/TT pol zeta mutational signature is the most frequent among DNMs, and its rate exceeds the mean rate of other DNM types by a factor of approximately 10. Unlike the overall rate of DNMs, the pol zeta signature drastically increases with the replication time in the human genome. Finally, the pol zeta signature is enriched in transcribed regions, and there is a strong prevalence of GC->TT over GC->AA DNMs on the nontemplate strand, indicating association with transcription. A recurrently occurring GC->TT DNM in HRAS and SOD1 genes causes the Costello syndrome and amyotrophic lateral sclerosis correspondently; we observe an approximately 1 kb long mutation hotspot enriched by transversions near these DNMs in both cases, suggesting a link between these diseases and pol zeta activity. This study uncovers the genomic preferences of pol zeta, shedding light on a novel cause of mutational heterogeneity along the genome. PMID- 26376650 TI - Stereoselective handling of perhexiline: implications regarding accumulation within the human myocardium. AB - PURPOSE: Perhexiline is a prophylactic anti-ischaemic agent with weak calcium antagonist effect which has been increasingly utilised in the management of refractory angina. The metabolic clearance of perhexiline is modulated by CYP2D6 metaboliser status and stereoselectivity. The current study sought to (1) determine whether the acute accumulation of perhexiline in the myocardium is stereoselective and (2) investigate the relationship between duration of short term therapy and the potential stereoselective effects of perhexiline within myocardium. METHOD: Patients (n = 129) from the active arm of a randomised controlled trial of preoperative perhexiline in cardiac surgery were treated with oral perhexiline for a median of 9 days. Correlates of atrial and ventricular concentrations of enantiomers were sought via univariate followed by multivariate analyses. RESULTS: Myocardial uptake of both (+) and (-) perhexiline was greater in ventricles than in atria, and there was more rapid clearance of (-) than (+) perhexiline. The main determinants of atrial uptake of both (+) and (-) perhexiline were the plasma concentrations [(+) perhexiline: beta = -0.256, p = 0.015; (-) perhexiline: beta = -0.347, p = 0.001] and patients' age [(+) perhexiline: beta = 0.300, p = 0.004; (-) perhexiline: beta = 0.288, p = 0.005]. Atrial uptake of (+) enantiomer also varied directly with duration of therapy (beta = 0.228, p = 0.025), while atrial uptake of (-) perhexiline varied inversely with simultaneous heart rate (beta = -0.240, p = 0.015). CONCLUSION: (1) Uptake of both perhexiline enantiomers into atrium is greater with advanced age and displays evidence of both saturability and minor stereoselectivity. (2) Atrial uptake of (-) perhexiline may selectively modulate heart rate reduction. PMID- 26376652 TI - Female doctors and scientists in US lag in faculty promotions and research funding, studies find. PMID- 26376653 TI - Non-contiguous meningeal metastases of olfactory neuroblastoma. AB - Olfactory neuroblastoma (ONB) is a malignant neoplasm centered along the roof of the nasal cavity near the cribriform plate. Although metastasis of this tumor has been reported, non-contiguous spread to the dura is rare. Here, we report the largest series of intracranial meningeal metastases of ONBs from M.D. Anderson Cancer Center and the University of Toronto. The unique natural history and geographical distribution of these metastatic lesions suggest a common mechanism of tumor spread along the dural vascular arborization. PMID- 26376654 TI - Location of brain tumor intersecting white matter tracts predicts patient prognosis. AB - Brain tumor cells invade adjacent normal brain along white matter (WM) bundles of axons. We therefore hypothesized that the location of tumor intersecting WM tracts would be associated with differing survival. This study introduces a method, voxel-wise survival analysis (VSA), to determine the relationship between the location of brain tumor intersecting WM tracts and patient prognosis. 113 primary glioblastoma (GBM) patients were retrospectively analyzed for this study. Patient specific tumor location, defined by contrast-enhancement, was combined with diffusion tensor imaging derived tractography to determine the location of axons intersecting tumor enhancement (AXITEs). VSA was then used to determine the relationship between the AXITE location and patient survival. Tumors intersecting the right anterior thalamic radiation (ATR), right inferior fronto-occipital fasciculus (IFOF), right and left cortico-spinal tract (CST), and corpus callosum (CC) were associated with decreased overall survival. Tumors intersecting the CST, body of the CC, right ATR, posterior IFOF, and inferior longitudinal fasciculus are associated with decreased progression-free survival (PFS), while tumors intersecting the right genu of the CC and anterior IFOF are associated with increased PFS. Patients with tumors intersecting the ATR, IFOF, CST, or CC had significantly improved survival prognosis if they were additionally treated with bevacizumab. This study demonstrates the usefulness of VSA by locating AXITEs associated with poor prognosis in GBM patients. This information should be included in patient-physician conversations, therapeutic strategy, and clinical trial design. PMID- 26376655 TI - Accuracy of Tokuhashi score system in predicting survival of lung cancer patients with vertebral metastasis. AB - Controversy exists in the accuracy of Tokuhashi score (TS) system in predicting survival of patients with vertebral metastasis, including vertebral metastases from primary lung cancer. To calculate the accuracy of the TS in predicting survival of lung cancer patients with vertebral metastasis and investigate which subgroup's survival is suitable for TS to predict, we conduct this retrospective study. From January 2008 to December 2013, 151 patients with vertebral metastases from primary lung cancer in our institute were included. The data were censored at December 2014. Patients were classified according to TS. The actual and predicted survivals were compared to calculate the accuracy rate. Spearman's correlation analysis was conducted to explore the relation between overall survival and TS. Cox regression was carried out to investigate potential factors affecting prognosis. Only 8.6 % (13 patients) actually followed the survivorship pattern as predicted by the TS. Spearman's correlation analysis demonstrated that actual overall survival correlated significantly with the TS. Cox model indicated that status of visceral metastases (i.e., none, involved with lung, involved with extrapulmonary organ) and response to first-time systemic therapy (effective or not) are associated significantly with overall survival. For patients with visceral metastases and progression to first-time systemic therapy simultaneously, predicted survival by TS and actual survival matched well. TS could only predict survival accurately in those with visceral metastases and disease progression to first-time systemic therapy simultaneously. Thus, it may not be a reliable tool to predict survival in lung cancer patients with vertebral metastasis. Status of visceral metastases and response to first-time systemic therapy should be added into TS system to increase validity and accuracy. PMID- 26376656 TI - Detecting the H3F3A mutant allele found in high-grade pediatric glioma by real time PCR. AB - Diffuse intrinsic pontine glioma (DIPG) is an aggressive pediatric brain tumor with a median survival of 1 year after diagnosis. It has been reported recently that about 80% of DIPG cases and 70% of midline glioblastomas contain a mutation at one allele of the H3F3A gene (encoding histone H3 variant H3.3), replacing the lysine 27 with methionine (K27M). In order to facilitate diagnosis of DIPG patients, a quick and reliable method to identify the H3F3A K27M mutation is needed. Here, we describe a real-time PCR-based procedure involving a mutant specific primer, a blocker oligonucleotide, and a reverse primer that can differentiate samples with H3F3A K27M mutation from those that do not. We first tested four different mutant-specific primers for their ability to selectively amplify H3F3A K27M-mutant allele and found that one primer amplified the mutant allele more efficiently than the rest. We then determined the optimal concentration of blocker oligo that significantly improved amplification of the H3F3A K27M-mutant allele. Using this optimized real-time PCR assay, we analyzed eleven samples, two of which containing H3F3A K27M mutation, and found that these two samples were differentially amplified from the nine others. In addition, we were able to discern the H3F3A K27M mutation in a newly obtained pediatric brainstem glioblastoma sample whose H3.3 status was not known previously, and in three other DIPG samples as well as paraffin embedded samples. These results demonstrate that we have developed a new reliable procedure for detecting the H3F3A K27M mutation in pediatric glioblastoma patient samples. PMID- 26376657 TI - A murine model of targeted infusion for intracranial tumors. AB - Historically, intra-arterial (IA) drug administration for malignant brain tumors including glioblastoma multiforme (GBM) was performed as an attempt to improve drug delivery. With the advent of percutaneous neuorovascular techniques and modern microcatheters, intracranial drug delivery is readily feasible; however, the question remains whether IA administration is safe and more effective compared to other delivery modalities such as intravenous (IV) or oral administrations. Preclinical large animal models allow for comparisons between treatment routes and to test novel agents, but can be expensive and difficult to generate large numbers and rapid results. Accordingly, we developed a murine model of IA drug delivery for GBM that is reproducible with clear readouts of tumor response and neurotoxicities. Herein, we describe a novel mouse model of IA drug delivery accessing the internal carotid artery to treat ipsilateral implanted GBM tumors that is consistent and reproducible with minimal experience. The intent of establishing this unique platform is to efficiently interrogate targeted anti-tumor agents that may be designed to take advantage of a directed, regional therapy approach for brain tumors. PMID- 26376659 TI - What course are we to expect for a child with her first manic episode? PMID- 26376658 TI - Whole-body MRI of patients with polymyalgia rheumatica identifies a distinct subset with complete patient-reported response to glucocorticoids. AB - OBJECTIVES: To determine whether whole-body MRI defines clinically relevant subgroups within polymyalgia rheumatica (PMR) including glucocorticoid responsiveness. METHODS: 22 patients with PMR and 16 with rheumatoid arthritis (RA), untreated and diagnosed by consultant rheumatologists, underwent whole body, multiple-joint MRI, scored by two experts. Patients with PMR reported whether they felt 'back to normal' on glucocorticoid therapy and were followed for a median of 2 years. RESULTS: All patients with PMR were deemed to respond to glucocorticoids clinically. A characteristic pattern of symmetrical, extracapsular inflammation, adjacent to greater trochanter, acetabulum, ischial tuberosity and/or symphysis pubis, was observed in 14/22 of the PMR cases. In PMR, this pattern was associated with complete glucocorticoid response (p=0.01), higher pretreatment C-reactive protein (CRP) and serum interleukin-6 (IL-6), and better post-treatment fatigue and function. Only 1/14 in the extracapsular group could stop glucocorticoids within 1 year, compared with 4/7 of the others. A score derived from the five sites discriminating best between PMR and RA correlated with IL-6 (p<0.002). IL-6 levels >=16.8 pg/mL had 86% sensitivity and 86% specificity for the extracapsular MRI pattern. CONCLUSIONS: A subset of patients with rheumatologist-diagnosed PMR had a characteristic, extracapsular pattern of MRI inflammation, associated with elevated IL-6/CRP and with complete patient-reported glucocorticoid responsiveness. PMID- 26376660 TI - Differential ant exclusion from canopies shows contrasting top-down effects on community structure. AB - Predators have far-reaching effects on communities by triggering top-down trophic cascades that influence ecosystem functioning. Omnivory and intraguild interactions between predators give rise to reticulate food webs and may either strengthen or dampen trophic cascades depending on context. Disentangling the effects of multiple predator species is therefore crucial for predicting the influence of predators on community structure. We focused on ants as dominant generalist predators in arthropod communities and set up a differential ant exclusion from canopies to examine its effects on assemblage species composition and densities of five arthropod groups (psocopterans, aphids, spiders, heteropterans and beetles). We coupled a glue band with tubes allowing only the ant Lasius grandis to reach the canopies to isolate its effect from the rest of crawling predators (ants, earwigs) and compared it against a full exclusion and a control. L. grandis alone had widespread effects on assemblage species composition, with contrasting species-specific responses within groups, where some species affected by L. grandis presence were not further affected by the presence of the whole crawling predator assemblage, and vice versa. Overall, L. grandis caused two- to threefold decreases of generalist predators and a threefold increase of aphids. However, it lacked further top-down effects on primary consumers, which only emerged when all crawling predators were present. This differential exclusion demonstrates the distinctive and widespread intraguild effects on community structure of a single ant species that contrast with the top-down effects exerted by the whole crawling predator assemblage. PMID- 26376661 TI - Conditional fitness benefits of the Rickettsia bacterial symbiont in an insect pest. AB - Inherited bacterial symbionts are common in arthropods and can have strong effects on the biology of their hosts. These effects are often mediated by host ecology. The Rickettsia symbiont can provide strong fitness benefits to its insect host, Bemisia tabaci, under laboratory and field conditions. However, the frequency of the symbiont is heterogeneous among field collection sites across the USA, suggesting that the benefits of the symbiont are contingent on additional factors. In two whitefly genetic lines collected from the same location, we tested the effect of Rickettsia on whitefly survival after heat shock, on whitefly competitiveness at different temperatures, and on whitefly competitiveness at different starting frequencies of Rickettsia. Rickettsia did not provide protection against heat shock nor affect the competitiveness of whiteflies at different temperatures or starting frequencies. However, there was a strong interaction between Rickettsia infection and whitefly genetic line. Performance measures indicated that Rickettsia was associated with significant female bias in both whitefly genetic lines, but in the second whitefly genetic line it conferred no significant fitness benefits nor conferred any competitive advantage to its host over uninfected whiteflies in population cages. These results help to explain other reports of variation in the phenotype of the symbiosis. Furthermore, they demonstrate the complex nature of these close symbiotic associations and the need to consider these interactions in the context of host population structure. PMID- 26376662 TI - Shielding Parenteral Nutrition From Light Improves Survival Rate in Premature Infants. AB - BACKGROUND: Intravenous nutrition preparations that are not photoprotected generate oxidants, which are deleterious for cell survival. The question remains: are these observations of clinical relevance in individuals receiving parenteral nutrition (PN), especially in those who exhibit immature antioxidant defenses such as premature infants? OBJECTIVE: To review clinical trials reporting the effect of light-exposed vs light-protected PN to determine whether photoprotection reduces neonatal mortality in preterm infants. DATA SOURCE: Electronic databases, abstracts in relevant journals, and references in manuscripts between 1980 and 2014. SELECTION CRITERIA: Newborn, premature infants, PN, photoprotection, shielding from light, randomization, mortality, death. METHODS: Consensus for inclusion reached by 2 reviewers; meta-analysis of trials and observational studies reporting mortality at 36 weeks' gestational age or hospital discharge. RESULTS: Four trials meeting selection criteria, which involved a total of 800 newborn premature infants, were included. Across trials, gestational age (mean +/- SD) ranged from 26 +/- 1 to 31 +/- 2 weeks, birth weight from 775 +/- 161 to 1588 +/- 366 g, and mortality from 5%-32%. Mortality in the light-protected group was half of that in the light-exposed group (95% confidence interval, 0.32-0.87) and twice as high in males compared with females (chi2, P = .01). CONCLUSION: Shielding PN from light has vital repercussions that call for action to provide photoprotected delivery systems and infusion sets in premature infants. Further studies should be extended to the increasing number of children and adults receiving long-term home PN to evaluate the effects of light protection on severe complications that impede their quality of life. PMID- 26376663 TI - Evidence for lung epithelial stem cell niches. AB - Recent studies have identified epithelial stem and progenitor cell populations of the lung. We are just beginning to understand the mechanisms that regulate their homeostatic, regenerative and maladaptive behaviors. Here, we discuss evidence of regulatory niches for epithelial stem cells of the lung. PMID- 26376664 TI - Comparison of Myelodysplastic Syndrome Prognostic Scoring Systems. AB - OBJECTIVE: Myelodysplastic syndrome (MDS) is a clonal hematopoietic stem cell disease. Patients are at risk of developing cytopenias or progression to acute myeloid leukemia. Different classifications and prognostic scoring systems have been developed. The aim of this study was to compare the different prognostic scoring systems. MATERIALS AND METHODS: One hundred and one patients who were diagnosed with primary MDS in 2003-2011 in a tertiary care university hospital's hematology department were included in the study. RESULTS: As the International Prognostic Scoring System (IPSS), World Health Organization Classification-Based Prognostic Scoring System (WPSS), MD Anderson Prognostic Scoring System (MPSS), and revised IPSS (IPSS-R) risk categories increased, leukemia-free survival and overall survival decreased (p<0.001). When the IPSS, WPSS, MPSS, and IPSS-R prognostic systems were compared by Cox regression analysis, the WPSS was the best in predicting leukemia-free survival (p<0.001), and the WPSS (p<0.001) and IPSS-R (p=0.037) were better in predicting overall survival. CONCLUSION: All 4 prognostic systems were successful in predicting overall survival and leukemia free survival (p<0.001). The WPSS was found to be the best predictor for leukemia free survival, while the WPSS and IPSS-R were found to be the best predictors for overall survival. PMID- 26376666 TI - Categorizations of migrants and ethnic minorities--are they useful for decisions on public health interventions? PMID- 26376668 TI - Twitter-Based Journal Clubs: Additional Facts and Clarifications. PMID- 26376667 TI - Heme Attenuation Ameliorates Irritant Gas Inhalation-Induced Acute Lung Injury. AB - AIMS: Exposure to irritant gases, such as bromine (Br2), poses an environmental and occupational hazard that results in severe lung and systemic injury. However, the mechanism(s) of Br2 toxicity and the therapeutic responses required to mitigate lung damage are not known. Previously, it was demonstrated that Br2 upregulates the heme degrading enzyme, heme oxygenase-1 (HO-1). Since heme is a major inducer of HO-1, we determined whether an increase in heme and heme dependent oxidative injury underlies the pathogenesis of Br2 toxicity. RESULTS: C57BL/6 mice were exposed to Br2 gas (600 ppm, 30 min) and returned to room air. Thirty minutes postexposure, mice were injected intraperitoneally with a single dose of the heme scavenging protein, hemopexin (Hx) (3 MUg/gm body weight), or saline. Twenty-four hours postexposure, saline-treated mice had elevated total heme in bronchoalveolar lavage fluid (BALF) and plasma and acute lung injury (ALI) culminating in 80% mortality after 10 days. Hx treatment significantly lowered heme, decreased evidence of ALI (lower protein and inflammatory cells in BALF, lower lung wet-to-dry weight ratios, and decreased airway hyperreactivity to methacholine), and reduced mortality. In addition, Br2 caused more severe ALI and mortality in mice with HO-1 gene deletion (HO-1-/-) compared to wild-type controls, while transgenic mice overexpressing the human HO-1 gene (hHO-1) showed significant protection. INNOVATION: This is the first study delineating the role of heme in ALI caused by Br2. CONCLUSION: The data suggest that attenuating heme may prove to be a useful adjuvant therapy to treat patients with ALI. PMID- 26376669 TI - Gene expression analysis in human polymorphonuclear leukocytes stimulated by LPSs from nosocomial opportunistic pathogens. AB - Innate immunity coordinates LPS detection via TLR4 on polymorphonuclear leukocytes (PMNs) to elicit responses to many Gram-negative bacteria. In this study, we describe the effects of five subtypes of LPS [isolated from Escherichia coli B4, Pseudomonas aeruginosa PAO1, multidrug-resistant P. aeruginosa (MDRP), Acinetobacter baumannii and multidrug-resistant A. baumannii (MDRA)] on gene expression in PMNs. LPS isolated from B4, PAO1, and A. baumannii did not significantly alter TLR2 expression. However, LPS from MDRP and MDRA caused a 0.6 fold decrease and 2.7-fold increase, respectively, in TLR2 expression. Similarly, TLR4 expression was not significantly altered by LPS isolated from B4, PAO1 and A. baumannii but was down-regulated by LPS isolated from MDRP and MDRA by 0.1- and 0.6-fold, respectively. All LPS subtypes, excluding PAO1, down-regulated CD14 expression in PMNs. However, all five LPS subtypes up-regulated TNFA, IL1B, IL6, IL10 and TREM1 expression in a concentration-dependent manner, with the most substantial responses observed following exposure to LPS from MDRP and MDRA. These different effects on the gene expression in PMNs may depend on variation in LPS structural modifications related to acquired drug resistance, such as acylation and/or glycosylation. PMID- 26376670 TI - Increased coupling interval variability -- mechanistic, diagnostic and prognostic implication of premature ventricular contractions and underlying heart diseases. PMID- 26376671 TI - Complete left bundle branch block and smaller left atrium are predictors of response to cardiac resynchronization therapy in advanced heart failure. AB - BACKGROUND: We previously reported that cardiac resynchronization therapy with defibrillator (CRT-D) is not an appropriate rescue strategy in patients with advanced heart failure (HF), especially those dependent on inotrope infusion, and instead early ventricular assist device (VAD) implantation should be considered. Predictors of response to CRT in such populations, however, remain uncertain. METHODS AND RESULTS: We studied 67 inpatients aged <65 years old with advanced HF, who received CRT-D between 2007 and 2014. Eleven patients (16%) were responders, in whom LVEF improved >10% at 6-month follow up. On logistic regression analysis, LA volume index (LAVI) <43 ml/m(2)(odds ratio (OR), 36.67; P=0.001) and complete left bundle branch block (CLBBB; OR, 6.663; P=0.032) were significant predictors of response to CRT-D among the baseline variables. Patients with both predictors were associated with improvements in LVEF and plasma B-type natriuretic peptide compared with those with none of these predictors during the 6-month follow up period (P<0.05 for both). VAD-free survival rate was significantly higher in the responders compared with the non responders during the 2-year study period (86% vs. 52%, P=0.044). CONCLUSIONS: CLBBB and smaller LAVI are novel predictors of response in patients with advanced HF receiving CRT-D in real-world practice. Such responders may be better candidates for CRT-D and delay of cardiac replacement therapy. PMID- 26376672 TI - Personal health monitoring - exploiting the power of the personal telephone. AB - Many health issues that we currently face are related to our lifestyle choices. Educating patients can help them to make better informed health decisions. The internet and smartphones, mobile telephones that perform many of the functions of a computer, are becoming more accessible to the majority of the population. Applications on smartphones and professional health websites can signpost patients to trusted information and allow them to co-produce records. Empowering patients, staff and organizations through enabling access to records and understanding, building a partnership trust and the use of social media can enable people to do more and hopefully improve outcomes. In this article, I describe the steps we have taken to facilitate such interactions within our own primary care practice and the response of patients to these initiatives. PMID- 26376673 TI - Missed nursing care is linked to patient satisfaction: a cross-sectional study of US hospitals. AB - BACKGROUND: As nurses are the principal care provider in the hospital setting, the completion or omission of nursing care is likely to have a sizable impact on the patient care experience. However, this relationship has not been explored empirically. AIM: To describe the prevalence and patterns of missed nursing care and explore their relationship to the patient care experience. METHODS: This cross-sectional study used secondary nurse and patient survey data from 409 adult non-federal acute care US hospitals in four states. Descriptive statistics were calculated and linear regression models were conducted at the hospital level. Regression models included controls for hospital structural characteristics. RESULTS: In an average hospital, nurses missed 2.7 of 12 required care activities per shift. Three-fourths (73.4%) of nurses reported missing at least one activity on their last shift. This percentage ranged from 25 to 100 across hospitals. Nurses most commonly reported not being able to comfort or talk with patients (47.6%) and plan care (38.5%). 6 out of 10 patients rated hospitals highly. This proportion ranged from 33% to 90% across hospitals. At hospitals where nurses missed more care (1 SD higher=0.74 items), 2.2% fewer patients rated the hospital highly (p<0.001); a coefficient equivalent to a one-quarter SD change. CONCLUSIONS: Missed nursing care is common in US hospitals and varies widely. Most patients rate their hospital care experience highly, but this also varies widely across hospitals. Patients have poorer care experiences in hospitals where more nurses miss required nursing care. Supporting nurses' ability to complete required care may optimise the patient care experience. As hospitals face changing reimbursement landscapes, ensuring adequate nursing resources should be a top priority. PMID- 26376674 TI - Coproduction of healthcare service. AB - Efforts to ensure effective participation of patients in healthcare are called by many names-patient centredness, patient engagement, patient experience. Improvement initiatives in this domain often resemble the efforts of manufacturers to engage consumers in designing and marketing products. Services, however, are fundamentally different than products; unlike goods, services are always 'coproduced'. Failure to recognise this unique character of a service and its implications may limit our success in partnering with patients to improve health care. We trace a partial history of the coproduction concept, present a model of healthcare service coproduction and explore its application as a design principle in three healthcare service delivery innovations. We use the principle to examine the roles, relationships and aims of this interdependent work. We explore the principle's implications and challenges for health professional development, for service delivery system design and for understanding and measuring benefit in healthcare services. PMID- 26376675 TI - From core/shell to hollow Fe/gamma-Fe2O3 nanoparticles: evolution of the magnetic behavior. AB - High quality Fe/gamma-Fe2O3 core/shell, core/void/shell, and hollow nanoparticles with two different sizes of 8 and 12 nm were synthesized, and the effect of morphology, surface and finite-size effects on their magnetic properties including the exchange bias (EB) effect were systematically investigated. We find a general trend for both systems that as the morphology changes from core/shell to core/void/shell, the magnetization of the system decays and inter-particle interactions become weaker, while the effective anisotropy and the EB effect increase. The changes are more drastic when the nanoparticles become completely hollow. Noticeably, the morphological change from core/shell to hollow increases the mean blocking temperature for the 12 nm particles but decreases for the 8 nm particles. The low-temperature magnetic behavior of the 12 nm particles changes from a collective super-spin-glass system mediated by dipolar interactions for the core/shell nanoparticles to a frustrated cluster glass-like state for the shell nanograins in the hollow morphology. On the other hand for the 8 nm nanoparticles core/shell and hollow particles the magnetic behavior is more similar, and a conventional spin glass-like transition is obtained at low temperatures. In the case of the hollow nanoparticles, the coupling between the inner and outer spin layers in the shell gives rise to an enhanced EB effect, which increases with increasing shell thickness. This indicates that the morphology of the shell plays a crucial role in this kind of exchange-biased systems. PMID- 26376676 TI - A novel anti-cancer agent Icaritin suppresses hepatocellular carcinoma initiation and malignant growth through the IL-6/Jak2/Stat3 pathway. AB - Tumor-initiating cell (TIC) is a subpopulation of cells in tumors that are responsible for tumor initiation and progression. Recent studies indicate that hepatocellular carcinoma-initiating cells (HCICs) confer the high malignancy, recurrence and multi-drug resistance in hepatocellular carcinoma (HCC). In this study, we found that Icaritin, a prenylflavonoid derivative from Epimedium Genus, inhibited malignant growth of HCICs. Icaritin decreased the proportion of EpCAM positive (a HCICs marker) cells, suppressed tumorsphere formation in vitro and tumor formation in vivo. We also found that Icaritin reduced expression of Interleukin-6 Receptors (IL-6Rs), attenuated both constitutive and IL-6-induced phosphorylation of Janus-activated kinases 2 (Jak2) and Signal transducer and activator of transcription 3 (Stat3), and inhibited Stat3 downstream genes, such as Bmi-1 and Oct4. The inhibitory activity of Icaritin in HCICs was augmented by siRNA-mediated silencing of Stat3 but attenuated by constitutive activation of Stat3.Taken together, our results indicate that Icaritin is able to inhibit malignant growth of HCICs and suggest that Icaritin may be developed into a novel therapeutic agent for effective treatment of HCC. PMID- 26376677 TI - miR675 upregulates long noncoding RNA H19 through activating EGR1 in human liver cancer. AB - microRNAs (miRNAs) are short non-coding RNAs that are involved in post transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miR675, embedded in H19's first exon, had been linked to the development of human cancers. Herein, we demonstrate miR675 overexpression promotes and silencing miR675 attenuated liver cancer cell growth in vitro and in vivo. Mechanistically, miR675 inhibits the heterochromatin1 isoform HP1alpha expression in human liver cancer cells which causes a dramatically decrease of the total histone H3 lysine 9 trimethylation (H3K9me3) , histone H3 lysine 27 trimethylation (H3K27me3) and a increase of histone H3 lysine 27 acetylation(H3K27Ac).Notably, a significant reduction of the H3K9me3 and H3K27me3 and the increment of H3K27Ac occupancy on the promoter region of EGR1 triggers EGR1 transcription, translation, sumoylation and activation which upregulates lincRNA H19. Strikingly, H19 may induce and activate tumor-specific pyruvate kinase M2 (PKM2) which is essential for the Warburg effect in its dimer and for gene expression in its teramer during tumorigenesis. Our results imply that miR675 is involved in the epigenetic regulation of H3K9me3, H3k27me3 and H3K27Ac for gene expression and function during hepatocarcinogenesis (e.g.C-myc,Pim1,Ras,CyclinD1,RB1).These findings sheds light on the significance of miR675-HP1alpha-EGR1-H19-PKM2 cascade signaling pathway in liver cancer. PMID- 26376678 TI - Effects of first- and second-generation tyrosine kinase inhibitor therapy on glucose and lipid metabolism in chronic myeloid leukemia patients: a real clinical problem? AB - BACKGROUND: Tyrosine kinase inhibitors (TKIs) have dramatically changed the prognosis of patients with chronic myeloid leukemia (CML). They have a distinct toxicity profile that includes glycometabolic alterations: i.e. diabetes mellitus (DM), impaired fasting glucose (IFG), and the metabolic syndrome (MS). The aim of this study was to evaluate the prevalence of these alterations in a cohort of CML chronic phase patients treated with imatinib, dasatinib or nilotinib. METHODS: The study involved 168 consecutive CML-chronic phase patients with no history of DM/IFG or MS. Anthropometric and metabolic parameters were assessed, and DM/IFG and MS were diagnosed based on the criteria of the American Diabetes Association and the National Cholesterol Education Program-Adult Treatment Panel III, respectively. RESULTS: The nilotinib group had significantly higher levels of fasting plasma glucose, insulin, C-peptide, insulin resistance, and total and LDL cholesterol than the imatinib and dasatinib groups. DM/IFG were identified in 25% of the imatinib- and dasatinib-treated patients, and 33% of those in the nilotinib cohort (p = 0.39 vs imatinib and p = 0.69 vs dasatinib). A diagnosis of MS was made in 42.4% of the imatinib-treated patients, 37.5% of the dasatinib treated patients, and 36.1% of the nilotinib-treated patients (p = 0.46 vs imatinib and p = 0.34 vs dasatinib). CONCLUSIONS: Treatment with nilotinib does not seem to induce DM/IFG or the MS to a significantly higher extent than imatinib or dasatinib, though it causes a worse glycometabolic profile. These findings suggest the need for a close monitoring of glucose and lipid metabolism and a multidisciplinary approach in patients treated with nilotinib. PMID- 26376679 TI - Reducing the probability of radiation-induced hepatic toxicity by changing the treatment modality from helical tomotherapy to fixed-beam intensity-modulated radiotherapy. AB - PURPOSE: To estimate and compare the risk of radiation-induced hepatic toxicity (RIHT) in helical tomotherapy and fixed-beam intensity-modulated radiotherapy (IMRT) for the treatment of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Twenty patients with unresectable HCC treated with tomotherapy were selected. We performed tomotherapy re-planning to reduce the non-target normal liver volume receiving a dose of more than 15 Gy (NTNL-V15Gy), and we created a fixed-beam IMRT plan (FB-P). We compared the dosimetric results as well as the estimated probability of RIHT among the tomotherapy initial plan (T-IP), the tomotherapy re-plan (T-RP), and the FB-P. RESULTS: Comparing the T-RP and FB-P, the homogeneity index was 0.11 better with the T-RP. However, the mean NTNL-V15Gy was 6.3% lower with the FB-P. These differences result in a decline in the probability of RIHT from 0.216 in the T-RP to 0.115 in the FB-P. In patients whose NTNL-V15Gy was higher than 43.2% with the T-RP, the probability of RIHT markedly reduced from 0.533 to 0.274. CONCLUSIONS: By changing the treatment modality from tomotherapy to fixed-beam IMRT, we could reduce the liver dose and the probability of RIHT without scarifying the target coverage, especially in patients whose liver dose is high. PMID- 26376682 TI - Genome-wide inbreeding estimation within Lebanese communities using SNP arrays. PMID- 26376680 TI - Efficiency of CD19 chimeric antigen receptor-modified T cells for treatment of B cell malignancies in phase I clinical trials: a meta-analysis. AB - Chimeric antigen receptor (CAR) modified T cells targeted CD19 showed promising clinical outcomes in treatment of B cell malignances such as chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia (ALL) and other indolent lymphomas. However, the clinical benefit varies tremendously among different trials. This meta-analysis investigated the efficacy (response rates and survival time) of CD19-CAR T cells in refractory B cell malignances in Phase I clinical trials. We searched publications between 1991 and 2014 from PubMed and Web of Science. Pooled response rates were calculated using random-effects models. Heterogeneity was investigated by subgroup analysis and meta-regression. Fourteen clinical trials including 119 patients were eligible for response rate evaluation, 62 patients in 12 clinical trials were eligible for progression-free survival analysis. The overall pooled response rate of CD19-CAR T cells was 73% (95% confidence interval [CI]: 46-94%). Significant heterogeneity across estimates of response rates was observed (p < 0.001, I2=88.3%). ALL patients have higher response rate (93%, 95% CI: 65-100%) than CLL (62%, 95% CI: 27-93%) and lymphoma patients (36%, 95% CI: 1-83%). Meta-regression analysis identified lymphodepletion and no IL-2 administrated T cells as two key factors associated with better clinical response. Lymphodepletion and higher infused CAR T cell number were associated with better prognosis. In conclusion, this meta-analysis showed a high clinical response rate of CD19-CAR T cell-based immunotherapy in treatment of refractory B cell malignancies. Lymphodepletion and increasing number of infused CD19-CAR T cells have positive correlations with the clinical efficiency, on the contrary, IL-2 administration to T cells is not recommended. PMID- 26376683 TI - The phenotype of congenital insensitivity to pain due to the NaV1.9 variant p.L811P. PMID- 26376684 TI - Enhanced MAF Oncogene Expression and Breast Cancer Bone Metastasis. AB - BACKGROUND: There are currently no biomarkers for early breast cancer patient populations at risk of bone metastasis. Identification of mediators of bone metastasis could be of clinical interest. METHODS: A de novo unbiased screening approach based on selection of highly bone metastatic breast cancer cells in vivo was used to determine copy number aberrations (CNAs) associated with bone metastasis. The CNAs associated with bone metastasis were examined in independent primary breast cancer datasets with annotated clinical follow-up. The MAF gene encoded within the CNA associated with bone metastasis was subjected to gain and loss of function validation in breast cancer cells (MCF7, T47D, ZR-75, and 4T1), its downstream mechanism validated, and tested in clinical samples. A multivariable Cox cause-specific hazard model with competing events (death) was used to test the association between 16q23 or MAF and bone metastasis. All statistical tests were two-sided. RESULTS: 16q23 gain CNA encoding the transcription factor MAF mediates breast cancer bone metastasis through the control of PTHrP. 16q23 gain (hazard ratio (HR) for bone metastasis = 14.5, 95% confidence interval (CI) = 6.4 to 32.9, P < .001) as well as MAF overexpression (HR for bone metastasis = 2.5, 95% CI = 1.7 to 3.8, P < .001) in primary breast tumors were specifically associated with risk of metastasis to bone but not to other organs. CONCLUSIONS: These results suggest that MAF is a mediator of breast cancer bone metastasis. 16q23 gain or MAF protein overexpression in tumors may help to select patients at risk of bone relapse. PMID- 26376685 TI - p16/Ki-67 Dual Stain Cytology for Detection of Cervical Precancer in HPV-Positive Women. AB - BACKGROUND: Human papillomavirus (HPV)-based cervical cancer screening requires triage markers to decide who should be referred to colposcopy. p16/Ki-67 dual stain cytology has been proposed as a biomarker for cervical precancers. We evaluated the dual stain in a large population of HPV-positive women. METHODS: One thousand five hundred and nine HPV-positive women screened with HPV/cytology cotesting at Kaiser Permanente California were enrolled into a prospective observational study in 2012. Dual stain cytology was performed on residual Surepath material, and slides were evaluated for dual stain-positive cells. Disease endpoints were ascertained from the clinical database at KPNC. We evaluated the clinical performance of the assay among all HPV-positive women and among HPV-positive, cytology-negative women. We used internal benchmarks for clinical management to evaluate the clinical relevance of the dual stain assay. We evaluated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the dual stain compared with Pap cytology. All statistical tests were two-sided. RESULTS: The dual stain had lower positivity (45.9%) compared with cytology at an ASC-US threshold (53.4%). For detection of CIN2+, the dual stain had similar sensitivity (83.4% vs 76.6%, P = .1), and statistically higher specificity (58.9% vs 49.6%, P < .001), PPV (21.0% vs 16.6%, P < .001), and NPV (96.4% vs 94.2%, P = .01) compared with cytology. Similar patterns were observed for CIN3+. Women with a positive test had high enough risk for referral to colposcopy, while the risk for women with negative tests was below a one-year return threshold based on current US management guidelines. CONCLUSION: Dual stain cytology showed good risk stratification for all HPV positive women and for HPV-positive women with normal cytology. Additional follow up is needed to determine how long dual stain negative women remain at low risk of precancer. PMID- 26376686 TI - Unmetabolized Folic Acid in Prediagnostic Plasma and the Risk of Colorectal Cancer. AB - Higher folate has been associated with a reduced colorectal cancer (CRC) risk, but excessive folate may promote tumor progression. The role of unmetabolized folic acid (UFA) from high folic acid consumption in carcinogenesis is largely unexplored. We evaluated prediagnostic plasma levels of UFA in relation to CRC risk in nested case-control studies (618 CRC case patients and 1207 matched control) with blood samples collected prior to folic acid fortification. UFA was detected in 21.4% of control UFA levels were not associated with CRC risk. Compared with undetectable levels, the multivariable relative risks (RRs) of CRC were 1.03 (95% confidence interval [CI] = 0.73 to 1.46) for less than 0.5 nmol/L and 1.12 (95% CI = 0.81 to 1.55) for 0.5 nmol/L or more (Ptrend = .32). A positive association between UFA levels and CRC risk was observed among men (RR = 1.57, 95% CI = 0.99 to 2.49 for >=0.5 nmol/L vs undetectable, Pinteraction = .04), and a positive association was also observed among those with the methylene tetrahydrofolate reductase (MTHFR) CT/TT genotype (RR = 2.20, 95% CI = 1.22 to 3.94 for >=0.5 nmol/L vs undetectable, Pinteraction=0.02). In conclusion, prediagnostic plasma levels of UFA from the prefortification period were not associated with risk of CRC. PMID- 26376688 TI - Message Formats, Numeracy, Risk Perceptions of Alcohol-Attributable Cancer, and Intentions for Binge Drinking Among College Students. AB - We conducted an experiment to examine whether risk perceptions of alcohol attributable cancer influence college students' binge-drinking intention and to explore how message formats (text, table, and graph) and numeracy influence risk perceptions of alcohol-attributable cancer. We found that a majority of participants (87%) perceive some risks of alcohol-attributable cancer. Risk messages in tabular and graphic formats are more effective in elevating risk perceptions, but there is no significant difference between these two formats. Numeracy and its interaction with message formats, however, do not predict risk perceptions. We recommend risk messages should be delivered using tabular or graphic formats to enhance risk perceptions. We also advocate the less-is-more principle in presenting risk information. PMID- 26376687 TI - Prognostic Value of 25-hydroxyvitamin D3 Levels at Diagnosis and During Follow-up in Melanoma Patients. AB - BACKGROUND: A low 25-hydroxyvitamin D3 (25(OH)D3) serum concentration at melanoma diagnosis might be associated with worse survival. We prospectively studied the prognostic value of 25(OH)D3 at diagnosis and during follow-up. METHODS: MelanCohort is a cohort of invasive melanoma patients. Serum 25(OH)D3 was measured by mass spectrometry and standardized on month of blood drawn, age, sex, and body mass index (BMI). Role of 25(OH)D3 levels and risk of relapse was analyzed in a Cox proportional hazards model adjusting for age, sex, BMI, and American Joint Committee on Cancer (AJCC) stage. All statistical tests were two sided. RESULTS: One thousand one hundred seventy-one patients were included. 25(OH)D3 levels at diagnosis (median = 49.0 nmol/L) were inversely correlated with prognostic factors such as AJCC stage (P < .001 Kruskal-Wallis), Breslow's thickness (P < .001 Spearman correlation), and ulceration (P < .001 Kruskal Wallis), but not with risk of relapse. Changes in 25(OH)D3 levels during follow up were associated with worse prognosis: With a third quartile Q3 of average change per year (-0.30 to 4.60 nmol/L/Y) used as reference, hazard ratios for the first, second, and fourth quarters were 1.94 (95% confidence interval [CI] = 1.36 to 2.76), 1.23 (95% CI = 0.85 to 1.78), and 1.61 (95% CI = 1.14 to 2.28), respectively. In sensitivity analyses, no changes were observed either by AJCC stage, number of 25(OH)D3 measures performed, or by 25(OH)D3 level at baseline. No evidence of reverse causation was identified. Analyses performed on overall survival yielded similar results. CONCLUSIONS: We show that 25(OH)D3 variation during follow-up is an independent melanoma prognostic marker, but not its level at diagnosis. Previously reported associations between low 25(OH)D3 level at diagnosis and poor prognosis seem to be due to insufficient adjustment for prognostic factors. PMID- 26376689 TI - D-index: A New Scoring System in Febrile Neutropenic Patients for Predicting Invasive Fungal Infections. AB - OBJECTIVE: Neutropenia is a critical risk factor for invasive fungal infections (IFIs). We retrospectively performed this study to assess the performance of the D-index, a new test that combines both the duration and the severity of neutropenia, in predicting IFIs among patients with acute myelogenous leukemia. ? MATERIALS AND METHODS: Fifteen patients with IFIs and 28 patients who did not develop IFIs were enrolled in the study. The D-index was defined as the area over the neutrophil curve, whereas the cumulative-D-index (c-D-index) was the area over the neutrophil curve from the start of neutropenia until the first clinical manifestation of IFI.? RESULTS: The D-index and the c-D-index tended to be significantly higher in patients with IFIs, with medians of 10,150 (range: 4000 22,000) and 5300 (range: 2300-22,200), respectively (p=0.037 and p=0.003, respectively). The receiver operating characteristic analyses showed that there was a cutoff point of 3875 for the D-index in predicting IFI; the sensitivity, specificity, and positive and negative predictive values were 100%, 67.9%, 35.4%, and 100%, respectively. There was also a cutoff point of 4225 for the c-D-index in predicting IFI; the sensitivity, specificity, and positive and negative predictive values for the c-D-index were 93.3%, 71.4%, 36.6%, and 98.4%. ? CONCLUSION: The D-index and especially the c-D-index could be useful tools with high negative predictive value to exclude as well as to predict IFIs in the management of neutropenic patients. PMID- 26376690 TI - Determinants of arterial stiffness progression in a Han-Chinese population in Taiwan: a 4-year longitudinal follow-up. AB - BACKGROUND: Arterial stiffness predicts the future risk of macro- and micro vascular diseases. Only a few studies have reported longitudinal changes. The present study aimed to investigate the progression rate of arterial stiffness and the factors influencing stiffness progression in a Han Chinese population residing in Taiwan. METHODS: The pulse wave velocity (PWV), elasticity modulus (Ep) and arterial stiffness index (beta) of the common carotid artery were measured in 577 stroke- and myocardial infarction-free subjects at baseline and after an average interval of 4.2 +/- 0.8 years. Stepwise multivariate linear regression was conducted to elucidate the predictors of stiffness progression. RESULTS: For both baseline and follow-up data, men had significantly higher values of PWV, Ep and beta in comparison to women. The progression rates of PWV, Ep and beta were faster in men, but the difference was not statistically significant (DeltaPWV = 0.20 +/- 0.20 and 0.18 +/- 0.20 m/s/yr; DeltaEp = 8.17 +/ 8.65 and 6.98 +/- 8.26 kPa/yr; Deltabeta = 0.70 +/- 0.64 and 0.67 +/- 0.56 for men and women, respectively). In the multivariate regression analyses, age, baseline stiffness parameters, baseline mean arterial pressure (MAP), baseline body mass index (BMI) and changes in MAP (DeltaMAP) were independent predictors of PWV and Ep progression. There was an inverse correlation between the stiffness parameters at baseline and their progression rate (correlation coefficient (r) = 0.12 to -0.33, p = 0.032-1.6 * 10(-16)). Changes in MAP (DeltaMAP) rather than baseline MAP were more strongly associated with PWV progression (p = 8.5 * 10( 24) and 1.9 * 10(-5) for DeltaMAP and baseline MAP, respectively). Sex-specific analyses disclosed that baseline BMI and changes in BMI (DeltaBMI) were significantly associated with stiffness progression in men (p = 0.010-0.026), but not in women. CONCLUSIONS: Aging and elevated blood pressure at baseline and during follow-up were the major determinants of stiffness progression in the Han Chinese population. For men, increased baseline BMI and changes in BMI were additional risk factors. PMID- 26376691 TI - Linking altered central pain processing and genetic polymorphism to drug efficacy in chronic low back pain. AB - BACKGROUND: Inability to predict the therapeutic effect of a drug in individual pain patients prolongs the process of drug and dose finding until satisfactory pharmacotherapy can be achieved. Many chronic pain conditions are associated with hypersensitivity of the nervous system or impaired endogenous pain modulation. Pharmacotherapy often aims at influencing these disturbed nociceptive processes. Its effect might therefore depend on the extent to which they are altered. Quantitative sensory testing (QST) can evaluate various aspects of pain processing and might therefore be able to predict the analgesic efficacy of a given drug. In the present study three drugs commonly used in the pharmacological management of chronic low back pain are investigated. The primary objective is to examine the ability of QST to predict pain reduction. As a secondary objective, the analgesic effects of these drugs and their effect on QST are evaluated. METHODS/DESIGN: In this randomized, double blinded, placebo controlled cross-over study, patients with chronic low back pain are randomly assigned to imipramine, oxycodone or clobazam versus active placebo. QST is assessed at baseline, 1 and 2 h after drug administration. Pain intensity, side effects and patients' global impression of change are assessed in intervals of 30 min up to two hours after drug intake. Baseline QST is used as explanatory variable to predict drug effect. The change in QST over time is analyzed to describe the pharmacodynamic effects of each drug on experimental pain modalities. Genetic polymorphisms are analyzed as co-variables. DISCUSSION: Pharmacotherapy is a mainstay in chronic pain treatment. Antidepressants, anticonvulsants and opioids are frequently prescribed in a "trial and error" fashion, without knowledge however, which drug suits best which patient. The present study addresses the important need to translate recent advances in pain research to clinical practice. Assessing the predictive value of central hypersensitivity and endogenous pain modulation could allow for the implementation of a mechanism-based treatment strategy in individual patients. TRIAL REGISTRATION: Clinicaltrials.gov, NCT01179828. PMID- 26376693 TI - Anticancer Opportunity Created by Loss of Tumor Suppressor Genes. AB - Deletion of oncosuppressors occurs frequently in the cancer genome. A great deal of effort has been made to therapeutically restore the lost function of oncosuppressors, with little clinically translatable success, however. Reassuringly, besides the disappointing restoration endeavors, oncosuppressor loss can be therapeutically exploited in several other ways, such as the "synthetic lethality" strategies and the "therapeutic vulnerability" created by codeletion of neighboring genes. The study by Liu et al showed that codeletion of p53 and a neighboring essential gene POLR2A rendered colon cancer cells highly sensitive to further inhibition of POLR2A both in vitro and in vivo In recent years, several studies have reported similar phenomenon in a wide range of cancer types. In this focus article, we will introduce several kinds of anticancer opportunities created by the loss of oncosuppressors and discuss their mechanisms. Given the frequency of oncosuppressor loss in cancer, its therapeutic exploitation rather merits further investigation and may open a new window for oncotherapy. PMID- 26376692 TI - A survey of tandem repeat instabilities and associated gene expression changes in 35 colorectal cancers. AB - BACKGROUND: Colorectal cancer is a major contributor to cancer morbidity and mortality. Tandem repeat instability and its effect on cancer phenotypes remain so far poorly studied on a genome-wide scale. RESULTS: Here we analyze the genomes of 35 colorectal tumors and their matched normal (healthy) tissues for two types of tandem repeat instability, de-novo repeat gain or loss and repeat copy number variation. Specifically, we study for the first time genome-wide repeat instability in the promoters and exons of 18,439 genes, and examine the association of repeat instability with genome-scale gene expression levels. We find that tumors with a microsatellite instable (MSI) phenotype are enriched in genes with repeat instability, and that tumor genomes have significantly more genes with repeat instability compared to healthy tissues. Genes in tumor genomes with repeat instability in their promoters are significantly less expressed and show slightly higher levels of methylation. Genes in well-studied cancer associated signaling pathways also contain significantly more unstable repeats in tumor genomes. Genes with such unstable repeats in the tumor-suppressor p53 pathway have lower expression levels, whereas genes with repeat instability in the MAPK and Wnt signaling pathways are expressed at higher levels, consistent with the oncogenic role they play in cancer. CONCLUSIONS: Our results suggest that repeat instability in gene promoters and associated differential gene expression may play an important role in colorectal tumors, which is a first step towards the development of more effective molecular diagnostic approaches centered on repeat instability. PMID- 26376694 TI - Evaluation of Dynamic Optical Projection of Acquired Luminescence for Sentinel Lymph Node Biopsy in Large Animals. AB - Open surgery requiring cytoreduction still remains the primary treatment course for many cancers. The extent of resection is vital for the outcome of surgery, greatly affecting patients' follow-up treatment including need for revision surgery in the case of positive margins, choice of chemotherapy, and overall survival. Existing imaging modalities such as computed tomography, magnetic resonance imaging, and positron emission tomography are useful in the diagnostic stage and long-term monitoring but do not provide the level of temporal or spatial resolution needed for intraoperative surgical guidance. Surgeons must instead rely on visual evaluation and palpation in order to distinguish tumors from surrounding tissues. Fluorescence imaging provides high-resolution, real time mapping with the use of a contrast agent and can greatly enhance intraoperative imaging. Here we demonstrate an intraoperative, real-time fluorescence imaging system for direct highlighting of target tissues for surgical guidance, optical projection of acquired luminescence (OPAL). Image alignment, accuracy, and resolution was determined in vitro prior to demonstration of feasibility for operating room use in large animal models of sentinel lymph node biopsy. Fluorescence identification of regional lymph nodes after intradermal injection of indocyanine green was performed in pigs with surgical guidance from the OPAL system. Acquired fluorescence images were processed and rapidly reprojected to highlight indocyanine green within the true surgical field. OPAL produced enhanced visualization for resection of lymph nodes at each anatomical location. Results show the optical projection of acquired luminescence system can successfully use fluorescence image capture and projection to provide aligned image data that is invisible to the human eye in the operating room setting. PMID- 26376695 TI - Overexpression of MAC30 is Resistant to Platinum-Based Chemotherapy in Patients With Non-Small Cell Lung Cancer. AB - Adjuvant platinum-based chemotherapy has developed its stability as the first line treatment in advanced non-small cell lung cancer (NSCLC). The objective of this study was to investigate the prognostic value of meningioma-associated protein (MAC30) on adjuvant platinum-based chemotherapeutic response and survival in patients with NSCLC. A total of 174 retrospective stage III B to IV Chinese patients with NSCLC were enrolled in the study. Among all cases, 85 patients were given platinum-based chemotherapy and another 89 patients received molecularly targeted therapy. The expression of MAC30 in tumor samples was confirmed via immunohistochemical staining to correlate with the therapeutic response and survival of patients. Patients having NSCLC with MAC30 overexpression showed a poorer response to platinum-based chemotherapy, while there was no prognostic value of MAC30 expression on molecularly targeted therapy. Further, patients receiving platinum-based chemotherapy with enhanced MAC30 expression exhibited shorter survival. A multivariate analysis exhibited that increased MAC30 expression was an independent prognostic factor for overall survival in patients having NSCLC with platinum-based chemotherapy. In conclusion, patients having NSCLC with higher MAC30 expression resisted to platinum-based chemotherapy and exhibited worse survival. PMID- 26376696 TI - Binding Specificity of Radiolabeled Cyclic Peptide 153Sm-DTPA-c(CGRRAGGSC) to MHCC97-H Human Liver Cancer Cells and its Antitumor Effects in vivo. AB - OBJECTIVE: This objective of this study is to investigate the effects of the radiolabeled cyclic peptide 153Sm-DTPA-c(CGRRAGGSC) on MHCC97-H human liver cancer cells in vitro and in vivo. METHODS: The protein expression levels were examined by Western blot analysis. Biological activity of 153Sm-DTPA-c(CGRRAGGSC) was assessed with the radioligand binding assay and competitive inhibition experiment. Subcellular localization of the cyclic peptide was observed by fluorescence microscopy. Animals were implanted with MHCC97-H cells and administered with 153Sm-DTPA-c(CGRRAGGSC). Hematoxylin and eosin staining, electron microscopy, and immunohistochemistry were performed to evaluate the effects of 153Sm-DTPA-c(CGRRAGGSC) on implanted tumors. RESULT: The expression levels of interleukin 11 receptor were significantly elevated, by 2-to 5-fold, in tumor cell lines, especially for MHCC97-H cells. Characterization of 153Sm-DTPA c(CGRRAGGSC) showed that the biological activity of the cyclic peptide was not altered after labeling, and the radiolabeled cyclic peptide exhibited sufficient binding affinity to interleukin 11 receptor . The cyclic peptide of c(CGRRAGGSC) was mainly distributed in the cytoplasm and on the cell membrane of MHCC97-H cells. The in vivo experiments showed that the tumor growth was significantly inhibited by the treatment of 153Sm-DTPA-c(CGRRAGGSC). The inhibitory effect of 153Sm-DTPA-c(CGRRAGGSC) on tumor growth was further confirmed by Hematoxylin and eosin staining, electron microscopy, and immunohistochemistry. Moreover, the expression levels of interleukin 11 receptor in implanted tumors were significantly decreased in the treatment groups. CONCLUSION: 153Sm-DTPA-c (CGRRAGGSC) could specifically bind to interleukin 11 receptor on MHCC97-H liver tumor cells, inhibiting the cell proliferation and inducing cellular apoptosis. These findings provide experimental evidence for the development of individual treatment of liver cancers, as well as recurrence and metastasis. PMID- 26376697 TI - Experimental Validation of Monte Carlo Simulations Based on a Virtual Source Model for TomoTherapy in a RANDO Phantom. AB - A virtual source model for Monte Carlo simulations of helical TomoTherapy has been developed previously by the authors. The purpose of this work is to perform experiments in an anthropomorphic (RANDO) phantom with the same order of complexity as in clinical treatments to validate the virtual source model to be used for quality assurance secondary check on TomoTherapy patient planning dose. Helical TomoTherapy involves complex delivery pattern with irregular beam apertures and couch movement during irradiation. Monte Carlo simulation, as the most accurate dose algorithm, is desirable in radiation dosimetry. Current Monte Carlo simulations for helical TomoTherapy adopt the full Monte Carlo model, which includes detailed modeling of individual machine component, and thus, large phase space files are required at different scoring planes. As an alternative approach, we developed a virtual source model without using the large phase space files for the patient dose calculations previously. In this work, we apply the simulation system to recompute the patient doses, which were generated by the treatment planning system in an anthropomorphic phantom to mimic the real patient treatments. We performed thermoluminescence dosimeter point dose and film measurements to compare with Monte Carlo results. Thermoluminescence dosimeter measurements show that the relative difference in both Monte Carlo and treatment planning system is within 3%, with the largest difference less than 5% for both the test plans. The film measurements demonstrated 85.7% and 98.4% passing rate using the 3 mm/3% acceptance criterion for the head and neck and lung cases, respectively. Over 95% passing rate is achieved if 4 mm/4% criterion is applied. For the dose-volume histograms, very good agreement is obtained between the Monte Carlo and treatment planning system method for both cases. The experimental results demonstrate that the virtual source model Monte Carlo system can be a viable option for the accurate dose calculation of helical TomoTherapy. PMID- 26376698 TI - Low-dose ofatumumab for rituximab-resistant nephrotic syndrome. AB - Drug resistant idiopathic nephrotic syndrome (DRNS) remains a therapeutic dilemma. In this pilot study, the efficacy of the new fully humanised, anti-CD20 monoclonal antibody ofatumumab was tested in 4 children with persistence of proteinuria for at least 12 months in spite of a full drug approach (including rituximab). We used a low-dose 2-infusion ofatumumab model (300+700 mg/1.73 m(2) 2 weeks apart) using specified premedication. Transient normalisation of proteinuria (persisting for 2 months) was achieved in 1 child while another presented stable remission after 12 months; both had normal renal function. The outcome was not modified in the remaining 2 children presenting an impaired renal function. These results demonstrate that low-dose ofatumumab may induce remittance of proteinuria in children with a long story of DRNS and normal renal function. Further studies are needed to test whether higher doses of ofatumumab can also modify proteinuria in patients with impaired renal function. PMID- 26376699 TI - From past sailors' eras to the present day: scurvy as a surprising manifestation of an uncommon gastrointestinal disease. AB - A 45-year-old man presented with follicular exanthema in his lower limbs, alternating bowel habits and significant weight loss. His medical history included seronegative arthritis, bipolar disease and an inconclusive diagnostic laparoscopy. Diagnostic work up revealed microcytic anaemia and multivitamin deficiency. Skin biopsy of the exanthema suggested scurvy. Owing to these signs of malabsorption, upper endoscopy with duodenal biopsies was performed, exhibiting villous atrophy and extensive periodic acid-Schiff-positive material in the lamina propria, therefore diagnosing Whipple's disease (WD). After starting treatment with ceftriaxone and co-trimoxazole, an impressive recovery was noted, as the wide spectrum of malabsorption signs quickly disappeared. After a year of antibiotics, articular and cutaneous manifestations improved, allowing the patient to stop taking corticosteroids and antidepressants. This truly unusual presentation reflects the multisystemic nature of WD, often leading to misdiagnosis of other entities. Scurvy is a rare finding in developed countries, but its presence should raise suspicion for small bowel disease. PMID- 26376700 TI - Acute necrotising ulcerative gingivitis in an immunocompromised young adult. AB - Acute necrotising ulcerative gingivitis is an acute onset disease characterised by ulceration, necrosis, pain and bleeding in gingival surfaces. It is predominantly seen in severely malnourished children and young adults with advanced HIV infection. We present a unique presentation in a young adult with high-grade osteogenic sarcoma. PMID- 26376701 TI - Unique case of pneumomediastinum due to penetrating injury to the mediastinum. AB - Pneumomediastinum is a rare condition, and mostly occurs following traumatic or iatrogenic tracheal and oesophageal perforation, but spontaneous pneumomediastinum has also been described. We report a case of a 17-year-old woman who presented with a penetrating neck wound after a fall down the stairs. She had an extensive pneumomediastinum without signs of tracheal or oesophageal laceration, rib fractures, pneumothorax or haematothorax. The contaminated wound was surgically explored and extensively lavaged. Prophylactic antibiotic treatment was given and the patient recovered without complications. Direct perforating trauma to the mediastinum is a severe entity, but can be treated by lavage and prophylactic antibiotic therapy. PMID- 26376702 TI - Rare presentation of orbital plasmablastic lymphoma with oral cavity involvement in an HIV-negative patient. AB - Plasmablastic lymphoma is described as a subtype of non-Hodgkin's lymphoma under the category of diffuse large B-cell lymphoma. It is classified by WHO as HIV associated lymphoma of the oral cavity. Several cases have been reported in non HIV patients with extra-oral involvement. The characteristic immunohistochemical markers are generally positive for CD138, CD38 and MUM1/IRF4, and negative or weakly positive for pan B-cell markersCD20, CD79a, PAX-5 and BCL-6. We report a rare case of orbital plasmablastic lymphoma with oral and oropharyngeal involvement where the immunohistochemical markers were positive for CD138, CD43, CD45, CD79a and MUM1. A small subset of markers was weakly positive for CD20, CD30 and kappa, and negative for CD10, BCL-6, CD4, CD56 and Epstein-Barr virus encoded small RNA (EBER). Our case reinforces the fact that plasmablastic lymphoma is a different entity of non-Hodgkin's lymphoma that cannot simply be classified under diffuse large B-cell lymphoma. It demands modification of the WHO classification. PMID- 26376703 TI - Nanowires as Building Blocks to Fabricate Flexible Thermoelectric Fabric: The Case of Copper Telluride Nanowires. AB - A general approach to fabricate nanowires based inorganic/organic composite flexible thermoelectric fabric using a simple and efficacious five-step vacuum filtration process is proposed. As an excellent example, the performance of freestanding flexible thermoelectric thin film using copper telluride nanowires/polyvinylidene fluoride (Cu1.75Te NWs/PVDF = 2:1) as building block is demonstrated. By burying the Cu1.75Te NWs into the PVDF polymer agent, the flexible fabric exhibits room-temperature Seebeck coefficient and electric conductivity of 9.6 MUV/K and 2490 S/cm, respectively, resulting in a power factor of 23 MUW/(mK(2)) that is comparable to the bulk counterpart. Furthermore, this NW-based flexible fabric can endure hundreds of cycles of bending tests without significant performance degradation. PMID- 26376704 TI - MicroRNA detection based on analyte triggered nanoparticle localization on a tetrahedral DNA modified electrode followed by hybridization chain reaction dual amplification. AB - We have constructed an ultrasensitive method for microRNA detection based on analyte triggered nanoparticle localization and hybridization chain reaction dual amplification. The limit of detection is 2 aM. Furthermore, the applicability of this method for microRNA assay in real samples is demonstrated by the analysis of cell lysates. PMID- 26376706 TI - adj-Dicarbachlorin, the first free base carbaporphyrinoid system with an internal methylene unit. AB - Base-catalyzed condensation of dicyclopentadienylmethane with a dipyrrylmethane dialdehyde gave a dicarbachlorin with an internal CH2 group. This unusual porphyrinoid retained highly diatropic characteristics and exhibited a porphyrin like UV-vis spectrum. PMID- 26376705 TI - Designing a gel-fiber composite to extract nanoparticles from solution. AB - The extraction of nanoscopic particulates from flowing fluids is a vital step in filtration processes, as well as the fabrication of nanocomposites. Inspired by the ability of carnivorous plants to use hair-like filaments to entrap species, we use computational modeling to design a multi-component system that integrates compliant fibers and thermo-responsive gels to extract particles from the surrounding solution. In particular, hydrophobic fibers are embedded in a gel that exhibits a lower critical solution temperature (LCST). With an increase in temperature, the gel collapses to expose fibers that self-assemble into bundles, which act as nanoscale "grippers" that bind the particles and draw them into the underlying gel. By varying the relative stiffness of the fibers, the fiber particle interaction strength and the shear rate in the solution, we identify optimal parameters where the particles are effectively drawn from the solution and remain firmly bound within the gel layer. Hence, the system can be harnessed in purifying fluids and creating novel hybrid materials that integrate nanoparticles with polymer gels. PMID- 26376707 TI - Glitter in a 2D monolayer. AB - We predict a highly stable and robust atomically thin gold monolayer with a hexagonal close packed lattice stabilized by metallic bonding with contributions from strong relativistic effects and aurophilic interactions. We have shown that the framework of the Au monolayer can survive 10 ps MD annealing simulations up to 1400 K. The framework is also able to survive large motions out of the plane. Due to the smaller number of bonds per atom in the 2D layer compared to the 3D bulk we observe significantly enhanced energy per bond (0.94 vs. 0.52 eV per bond). This is similar to the increase in bond strength going from 3D diamond to 2D graphene. It is a non-magnetic metal, and was found to be the global minima in the 2D space. Phonon dispersion calculations demonstrate high kinetic stability with no negative modes. This 2D gold monolayer corresponds to the top monolayer of the bulk Au(111) face-centered cubic lattice. The close-packed lattice maximizes the aurophilic interactions. We find that the electrons are completely delocalized in the plane and behave as 2D nearly free electron gas. We hope that the present work can inspire the experimental fabrication of novel free standing 2D metal systems. PMID- 26376708 TI - Expansion of the hexagonal phase-forming region of Lu1-xScxFeO3 by containerless processing. AB - Hexagonal Lu1-xScxFeO3 (0 <= x <= 0.8) was directly solidified from an undercooled melt by containerless processing with an aerodynamic levitation furnace. The hexagonal phase-forming region was considerably extended compared to that of the conventional solid-state reaction (x ~ 0.5). Synchrotron X-ray diffraction measurements revealed that the crystal structure of the hexagonal phase was isomorphous to hexagonal ferroelectric RMnO3 (R = a rare earth ion) with a polar space group of P63cm. As x increased, the a-axis lattice constant decreased linearly, strengthening the antiferromagnetic interaction between the Fe(3+) ions on the a-b plane. Accordingly, the weak ferromagnetic transition temperature increased from 150 K for x = 0 to 175 K for x = 0.7. These transition temperatures were much higher than those of hexagonal Lu1-xScxMnO3. The results indicate that hexagonal Lu1-xScxFeO3 is a suitable alternative magnetic dielectric for use at higher temperatures. PMID- 26376709 TI - The complete mitochondrial genome of Pseudanoplocephala crawfordi and a comparison with closely related cestode species. AB - Pseudanoplocephala crawfordi is an important zoonotic cestode of economic significance and public health concern. In spite of its significance as a pathogen, the systematics, genetics, epidemiology and biology of this parasite remain poorly understood. In the present study, we sequenced and characterized the complete mitochondrial (mt) genome of P. crawfordi, which is 14,192 bp long and encodes 36 genes, including 12 protein-coding genes, 22 transfer RNA genes and two ribosomal RNA genes. Phylogenetic analysis of the concatenated amino acid sequences using the Bayesian inference (BI) method showed that P. crawfordi was closely related to the family Hymenolepididae. Considering that the taxonomic status of P. crawfordi has been controversial when based only on morphological features, the mt genome obtained here will provide novel molecular markers to ascertain the phylogenetic position of this parasite accurately. PMID- 26376710 TI - The Feasibility of Magnetic Resonance Imaging for Quantification of Liver, Pancreas, Spleen, Vertebral Bone Marrow, and Renal Cortex R2* and Proton Density Fat Fraction in Transfusion-Related Iron Overload. AB - OBJECTIVE: We aimed to evaluate the feasibility of quantification of liver, pancreas, spleen, vertebral bone marrow, and renal cortex R2* and magnetic resonance imaging-proton density fat fraction (MRI-PDFF) and to evaluate the correlations among them in patients with transfusion-related iron overload. MATERIALS AND METHODS: A total of 9 patients (5 boys, 4 girls) who were referred to our clinic with suspicion of hepatic iron overload were included in this study. All patients underwent T1-independent volumetric multi-echo gradient-echo imaging with T2* correction and spectral fat modeling. MRI examinations were performed on a 1.5 T MRI system. RESULTS: All patients had hepatic iron overload. Severe hepatic iron overload was recorded in 5/9 patients (56%), and when we evaluated the PDFF maps of these patients, we observed an extensive patchy artifact in the liver in 4 of 5 patients (R2* greater than 671 Hz). When we performed MRI-PDFF measurements despite these artifacts, we observed artifactual high MRI-PDFF values. There was a close correlation between average pancreas R2* and average pancreas MRI-PDFF (p=0.003, r=0.860). There was a significant correlation between liver R2* and average pancreas R2* (p=0.021, r=0.747), liver R2* and renal cortex R2* (p=0.020, r=0.750), and average pancreas R2* and renal cortex R2* (p=0.003, r=0.858). There was a significant negative correlation between vertebral bone marrow R2* and age (p=0.018, r=-0.759). CONCLUSION: High iron content of the liver, especially with a T2* value shorter than the first echo time can spoil the efficacy of PDFF calculation. Fat deposition in the pancreas is accompanied by pancreatic iron overload. There is a significant correlation between hepatic siderosis and pancreatic siderosis. Renal cortical and pancreatic siderosis are correlated, too. PMID- 26376711 TI - Understanding the growth and composition evolution of gold-seeded ternary InGaAs nanowires. AB - InGaAs nanowires offer great promise in fundamental studies of ternary compound semiconductors with variable composition and opens up a wide range of applications due to their bandgap tunability and high carrier mobility. Here, we report a study on the growth of Au-seeded InGaAs nanowires by metal-organic vapour phase epitaxy and present a model to explain the mechanisms that govern the growth and composition evolution in ternary III-V nanowires. The model allows us to further understand the limitations on the growth rate and incorporation of the two group III species imposed by the deposition conditions and some intrinsic properties of the material transport and nucleation. Within the model, the evolution of InGaAs nanowire growth rate and composition with particle size, temperature and V/III ratio is described and correlates very well with experimental findings. The understanding gained in this study should be useful for the controlled fabrication of tunable ternary nanowires for various applications. PMID- 26376712 TI - T2 signal intensity and volume abnormalities of hippocampal subregions in patients with amnestic mild cognitive impairment by magnetic resonance imaging. AB - BACKGROUND: The volumetry of the hippocampal subregion may provide additional information in the early investigation of amnestic mild cognitive impairment (aMCI) and the T2 signal intensity (T2-SI) of the hippocampal subregion has not been well studied quantitatively by magnetic resonance imaging (MRI) in aMCI. METHODS: Using combined MRI-based hippocampal volumetry and T2-SI at the levels of the whole hippocampus and hippocampal subregion, 18 patients with aMCI and 18 age-matched controls were investigated. RESULTS: Significantly lower left whole hippocampal and hippocampal head volumes and higher T2-SI in the bilateral whole hippocampus and hippocampal head were shown, whereas atrophy of the right whole hippocampus and hippocampal subregion was not significant in aMCI. Additionally, correlations were found among the hippocampal volume, T2-SI and Mini-Mental State Examination (MMSE) scores for aMCI in the whole hippocampus and some hippocampal subregions and an almost perfect correlation was found between T2-SI of the left hippocampal head and MMSE scores regarding aMCI (r = -0.831, P = 0.000). CONCLUSION: Abnormalities of the hippocampal volume and T2-SI were documented in aMCI, whereas T2-SI was implied to be more susceptible than the volume in the pathohistological progression in aMCI. Additionally, T2-SI in the left hippocampal head may be a potential biomarker to facilitate the early diagnosis of aMCI. PMID- 26376713 TI - Molecular malaria diagnostics: A systematic review and meta-analysis. AB - Accurate diagnosis of malaria is essential for identification and subsequent treatment of the disease. Currently, microscopy and rapid diagnostic tests are the most commonly used diagnostics, next to treatment based on clinical signs only. These tests are easy to deploy, but have a relatively high detection limit. With declining prevalence in many areas, there is an increasing need for more sensitive diagnostics. Molecular tools may be a suitable alternative, although costs and technical requirements currently hamper their implementation in resource limited settings. A range of (near) point-of-care diagnostics is therefore under development, including simplifications in sample preparation, amplification and/or read-out of the test. Accuracy data, in combination with technical characteristics, are essential in determining which molecular test, if any, would be the most promising to be deployed. This review presents a comprehensive overview of the currently available molecular malaria diagnostics, ranging from well-known tests to platforms in early stages of evaluation, and systematically evaluates their published accuracy. No important difference in accuracy was found between the most commonly used PCR-based assays (conventional, nested and real-time PCR), with most of them having high sensitivity and specificity, implying that there are no reasons other than practical ones to choose one technique over the other. Loop-mediated isothermal amplification and other (novel) diagnostics appear to be highly accurate as well, with some offering potential to be used in resource-limited settings. PMID- 26376714 TI - The new impact factor has arrived. Who cares? PMID- 26376717 TI - Acute hemorrhagic leukoencephalitis (Weston-Hurst syndrome) in a patient with relapse-remitting multiple sclerosis. AB - Acute hemorrhagic leukoencephalitis is a fulminant demyelinating disease and commonly considered as a rare and severe variant of acute disseminated encephalomyelitis. Here, we report the clinical, magnetic resonance imaging, and brain biopsy findings of a 35-year-old female with relapsing-remitting multiple sclerosis, who developed acute hemorrhagic leukoencephalitis. Magnetic resonance imaging revealed symmetrical hemorrhagic lesions in the basal ganglia including the thalami. Disease progression was consistent with acute hemorrhagic leukoencephalitis with rapid deterioration of consciousness and seizures. Besides hemorrhage, infiltration of neutrophils was detected in brain biopsy.Acute hemorrhagic leukoencephalitis, also known as Weston-Hurst syndrome, is an excessive immunological response of unknown etiology. So far, an association with multiple sclerosis has not been reported. The present case raises the question, whether acute hemorrhagic leukoencephalitis is a specific hyperacute form of acute disseminated encephalomyelitis, a severe and unspecific form of an immune response in the central nervous system, or belongs to the spectrum of tumefactive multiple sclerosis. PMID- 26376718 TI - Light-enhanced bioaccumulation of molybdenum by nitrogen-deprived recombinant anoxygenic photosynthetic bacterium Rhodopseudomonas palustris. AB - As molybdenum (Mo) is an indispensable metal for plant nitrogen metabolisms, accumulation of dissolved Mo into bacterial cells may connect to the development of bacterial fertilizers that promote plant growth. In order to enhance Mo bioaccumulation, nitrogen removal and light illumination were examined in anoxygenic photosynthetic bacteria (APB) because APB possess Mo nitrogenase whose synthesis is strictly regulated by ammonium ion concentration. In addition, an APB, Rhodopseudomonas palustris, transformed with a gene encoding Mo-responsive transcriptional regulator ModE was constructed. Mo content was most markedly enhanced by the removal of ammonium ion from medium and light illumination while their effects on other metal contents were limited. Increases in contents of trace metals including Mo by the genetic modification were observed. Thus, these results demonstrated an effective way to enrich Mo in the bacterial cells by the culture conditions and genetic modification. PMID- 26376719 TI - Nutrition: a key environmental dietary factor in clinical severity and cardio metabolic risk in psoriatic male patients evaluated by 7-day food-frequency questionnaire. AB - BACKGROUND: Western dietary pattern is included among the environmental dietary factors involved in the pathogenesis of psoriasis. Nutritional data collection methods and gender differences might affect the association between diet and psoriasis. The 7-day food records is considered the "gold standard" of self administered food frequency questionnaires. In this study, we evaluated the differences in the dietary intake, anthropometric measurements and cardio metabolic risk profile in a group of psoriatic patients compared with an age and Body Mass Index (BMI)-matched control group. In addition, in the group of psoriatic patients we investigated the association between the dietary intake and clinical severity of psoriasis. METHODS: Cross-sectional case control observational study. A total of 82 adult males, 41 treatment-naive patients with psoriasis and 41 healthy subjects matched for age and BMI were included in the study. The clinical severity of psoriasis was by assessed by Psoriasis Area and Severity Index (PASI) score. The dietary interview data were collected by a 7-day food records. Anthropometric measures, glucose and lipid profile, liver function tests and C-reactive protein levels were measured. Homeostasis Model Assessment of Insulin Resistance (HoMA-IR), Visceral Adiposity Index (VAI) and the Fatty Liver Index (FLI) were calculated. RESULTS: Psoriatic patients consumed a higher percentage of total and simple carbohydrates, total fat, polyunsaturated fatty acid (PUFA) and n-6/n-3 PUFAs ratio, and cholesterol, while the consumption of protein, complex carbohydrates, monounsaturated fatty acid (MUFA), n-3 PUFA and fiber was lower than in the control group. In addition, psoriatic patients presented altered anthropometric measurements, glucose and lipid profile, liver function tests, and elevated values of HoMA-IR, VAI and FLI. PASI score well correlated with anthropometric measures, glucose and lipid profile, liver function tests, cardio-metabolic indices, and the dietary components, except for protein and total carbohydrates. At logistic regression analysis between PASI score and MUFA, MetS presence was well predicted only by higher PASI score (OR = 1.794; p = 0.002; CI 1.242-2.591). At multiple regression analysis, MUFA was the best predictor of PASI score (r(2) = 0.387, beta = -0.635, t = -5.127, p < 0.001). CONCLUSION: Differences in dietary intake were observed in adult male psoriatic patients compared with the controls. These differences were associated to the severity of the psoriasis and cardio-metabolic risk. FLI represented an early indicator of the cardio-metabolic risk profile in psoriatic patients, and dietary MUFA were major predictor of the clinical severity of psoriasis, while the association between psoriasis and metabolic syndrome appeared to be independent of MUFA intake. The low MUFA consumption might act as a possible adjunctive mechanism in increasing the inflammation milieu of psoriatic patients. PMID- 26376720 TI - Impaired survival of regulatory T cells in pulmonary sarcoidosis. AB - BACKGROUND: Impaired regulatory T cell (Treg) function is thought to contribute to ongoing inflammatory responses in sarcoidosis, but underlying mechanisms remain unclear. Moreover, it is not known if increased apoptotic susceptibility of Tregs may contribute to an impaired immunosuppressive function in sarcoidosis. Therefore, the aim of this study is to analyze proportions, phenotype, survival, and apoptotic susceptibility of Tregs in sarcoidosis. METHODS: Patients with pulmonary sarcoidosis (n = 58) were included at time of diagnosis. Tregs were analyzed in broncho-alveolar lavage fluid and peripheral blood of patients and healthy controls (HC). RESULTS: In sarcoidosis patients no evidence was found for a relative deficit of Tregs, neither locally nor systemically. Rather, increased proportions of circulating Tregs were observed, most prominently in patients developing chronic disease. Sarcoidosis circulating Tregs displayed adequate expression of FoxP3, CD25 and CTLA4. Remarkably, in sarcoidosis enhanced CD95 expression on circulating activated CD45RO(+) Tregs was observed compared with HC, and proportions of these cells were significantly increased. Specifically sarcoidosis Tregs--but not Th cells--showed impaired survival compared with HC. Finally, CD95L-mediated apoptosis was enhanced in sarcoidosis Tregs. CONCLUSION: In untreated patients with active pulmonary sarcoidosis, Tregs show impaired survival and enhanced apoptotic susceptibility towards CD95L. Increased apoptosis likely contributes to the insufficient immunosuppressive function of sarcoidosis Tregs. Further research into this field will help determine whether improvement of Treg survival holds a promising new therapeutic approach for chronic sarcoidosis patients. PMID- 26376721 TI - Pirt contributes to uterine contraction-induced pain in mice. AB - Uterine contraction-induced pain (UCP) represents a common and severe form of visceral pain. Nerve fibers that innervate uterine tissue express the transient receptor potential vanilloid channel 1 (TRPV1), which has been shown to be involved in the perception of UCP. The phosphoinositide-interacting regulator of TRP (Pirt) may act as a regulatory subunit of TRPV1. The intraperitoneal injection of oxytocin into female mice after a 6-day priming treatment with estradiol benzoate induces writhing responses, which reflect the presence of UCP. Here, we first compared writhing response between Pirt (+/+) and Pirt (-/-) mice. Second, we examined the innervation of Pirt-expressing nerves in the uterus of Pirt (-/-) mice by immunofluorescence and two-photon microscopy. Third, we identified the soma of dorsal root ganglion (DRG) neurons that innerve the uterus using retrograde tracing and further characterized the neurochemical properties of these DRG neurons. Finally, we compared the calcium response of capsaicin between DRG neurons from Pirt (+/+) and Pirt (-/-) mice. We found that the writhing responses were less intensive in Pirt (-/-) mice than in Pirt (+/+) mice. We also observed Pirt-expressing nerve fibers in the myometrium of the uterus, and that retrograde-labeled cells were small-diameter, unmyelinated, and Pirt-positive DRG neurons. Additionally, we found that the number of capsaicin responding neurons and the magnitude of evoked calcium response were markedly reduced in DRG neurons from Pirt (-/-) mice. Taken together, we speculate that Pirt plays an important role in mice uterine contraction-induced pain. PMID- 26376722 TI - THAM reduces CO2-associated increase in pulmonary vascular resistance - an experimental study in lung-injured piglets. AB - INTRODUCTION: Low tidal volume (VT) ventilation is recommended in patients with acute respiratory distress syndrome (ARDS). This may increase arterial carbon dioxide tension (PaCO2), decrease pH, and augment pulmonary vascular resistance (PVR). We hypothesized that Tris(hydroxymethyl)aminomethane (THAM), a pure proton acceptor, would dampen these effects, preventing the increase in PVR. METHODS: A one-hit injury ARDS model was established by repeated lung lavages in 18 piglets. After ventilation with VT of 6 ml/kg to maintain normocapnia, VT was reduced to 3 ml/kg to induce hypercapnia. Six animals received THAM for 1 h, six for 3 h, and six serving as controls received no THAM. In all, the experiment continued for 6 h. The THAM dosage was calculated to normalize pH and exhibit a lasting effect. Gas exchange, pulmonary, and systemic hemodynamics were tracked. Inflammatory markers were obtained at the end of the experiment. RESULTS: In the controls, the decrease in VT from 6 to 3 ml/kg increased PaCO2 from 6.0+/-0.5 to 13.8+/-1.5 kPa and lowered pH from 7.40+/-0.01 to 7.12+/-0.06, whereas base excess (BE) remained stable at 2.7+/-2.3 mEq/L to 3.4+/-3.2 mEq/L. In the THAM groups, PaCO2 decreased and pH increased above 7.4 during the infusions. After discontinuing the infusions, PaCO2 increased above the corresponding level of the controls (15.2+/ 1.7 kPa and 22.6+/-3.3 kPa for 1-h and 3-h THAM infusions, respectively). Despite a marked increase in BE (13.8+/-3.5 and 31.2+/-2.2 for 1-h and 3-h THAM infusions, respectively), pH became similar to the corresponding levels of the controls. PVR was lower in the THAM groups (at 6 h, 329+/-77 dyn?s/m(5) and 255+/ 43 dyn?s/m(5) in the 1-h and 3-h groups, respectively, compared with 450+/-141 dyn?s/m(5) in the controls), as were pulmonary arterial pressures. CONCLUSIONS: The pH in the THAM groups was similar to pH in the controls at 6 h, despite a marked increase in BE. This was due to an increase in PaCO2 after stopping the THAM infusion, possibly by intracellular release of CO2. Pulmonary arterial pressure and PVR were lower in the THAM-treated animals, indicating that THAM may be an option to reduce PVR in acute hypercapnia. PMID- 26376724 TI - Tunneling and Parity Violation in Trisulfane (HSSSH): An Almost Ideal Molecule for Detecting Parity Violation in Chiral Molecules. AB - Measuring the parity-violating energy difference Deltapv E between the enantiomers of chiral molecules is a major challenge of current physical-chemical stereochemistry. An important step towards this goal is to identify suitable molecules for such experiments by means of theory. This step has been made by calculations for the complex dynamics of tunneling and electroweak quantum chemistry of parity violation in the "classic" molecule trisulfane, HSSSH, which satisfies the relevant conditions for experiments almost ideally, as the molecule is comparatively simple and parity violation clearly dominates over tunneling in the ground state. At the same time, the barrier for stereomutation is easily overcome by the S-H infrared chromophore. PMID- 26376723 TI - Essential oil from Xylopia frutescens Aubl. reduces cytosolic calcium levels on guinea pig ileum: mechanism underlying its spasmolytic potential. AB - BACKGROUND: Xylopia frutescens Aubl. (embira, semente-de-embira or embira vermelha), is used in folk medicine as antidiarrheal. The essential oil from its leaves (XF-EO) has been found to cause smooth muscle relaxation. Thus, the aim of this study was to investigate the spasmolytic action by which XF-EO acts on guinea pig ileum. METHODS: The components of the XF-EO were identified by gas chromatography-mass spectrometry. Segments of guinea pig ileum were suspended in organ bath containing modified Krebs solution at 37 degrees C, bubbled with carbogen mixture under a resting tension of 1 g. Isotonic contractions were registered using kymographs and isometric contractions using force transducer coupled to an amplifier and computer. Fluorescence measurements were obtained with a microplate reader using Fluo-4. RESULTS: Forty-three constituents were identified in XF-EO, mostly mono- and sesquiterpenes. XF-EO has been found to cause relaxation on guinea pig ileum. The essential oil inhibited in a concentration-dependent manner both CCh- and histamine-induced phasic contractions, being more potent on histamine-induced contractions as well as antagonized histamine-induced cumulative contractions in a non-competitive antagonism profile. XF-EO relaxed in a concentration-dependent manner the ileum pre-contracted with KCl and histamine. Since the potency was smaller in organ pre contracted with KCl, it was hypothesized that XF-OE would be acting as a K(+) channel positive modulator. In the presence of CsCl (non-selective K(+) channel blocker), the relaxant potency of XF-OE was not altered, indicating a non participation of these channels. Moreover, XF-EO inhibited CaCl2-induced cumulative contractions in a depolarizing medium nominally without Ca(2+) and relaxed the ileum pre-contracted with S-(-)-Bay K8644 in a concentration dependent manner, thus, was confirmed the inhibition of Ca(2+) influx through Cav1 by XF-EO. In cellular experiments, the viability of longitudinal layer myocytes from guinea pig ileum was not altered in the presence of XF-OE and the Fluo-4-associated fluorescence intensity in these intestinal myocytes stimulated by histamine was reduced by the essential oil, indicating a [Ca(2+)]c reduction. CONCLUSION: Spasmolytic action mechanism of XF-EO on guinea pig ileum can involve histaminergic receptor antagonism and Ca(2+) influx blockade, which results in [Ca(2+)]c reduction leading to smooth muscle relaxation. PMID- 26376725 TI - Correlations between self-rating and observer-rating of psychopathology in at risk mental state and first-episode psychosis patients: influence of disease stage and gender. AB - AIM: Research findings on the correlations between self-rating and observer rating of schizophrenic psychopathology are inconsistent and have rarely considered first-episode psychosis (FEP) and at-risk mental state (ARMS) for psychosis patients. This study investigates these correlations in ARMS and FEP patients and how they are moderated by disease stage and gender. METHODS: In the Basel Fruherkennung von Psychosen (FePsy) study, positive and negative psychotic and affective symptoms were rated in 126 ARMS and 94 FEP patients using two observer- and three self-rating scales. The agreement between self-rating and observer-rating and the moderating influence of disease stage and gender was quantified using Pearson correlation and multiple regression models. RESULTS: Correlations between self- and observer-rated subscales covering the same symptom dimension were low and mostly non-significant except for one correlation of positive and one of negative symptoms. There was no moderating influence of disease stage and gender on the correlations between self-rating and observer rating except for one higher association in positive symptoms in FEP compared to ARMS and in women compared to men. However, these significant interaction effects did not withstand correction for multiple testing. CONCLUSIONS: This study suggests that the agreement between self-rating and observer-rating in FEP and ARMS patients is rather low, similar across symptom dimensions, and only partially dependent on disease stage and gender. However, low correlations between self-rating and observer-rating do not necessarily indicate that these patients have difficulties reporting their symptoms. They could also have occurred because the scales did not exactly cover the same symptom dimensions. PMID- 26376726 TI - Successful palliation for an aged patient with primary pericardial mesothelioma. AB - An 85-year-old Japanese man with a complaint of exertional dyspnea was admitted to our hospital. Sixty-three years prior to admission at our hospital, he handled asbestos for 2 years in a factory. His chest computed tomography showed a massive pericardial effusion leading to cardiac tamponade and right pleural plaque. After a pericardiocentesis was performed, he recovered from cardiac failure caused by the cardiac tamponade. Pathological examination of the pericardial effusion revealed malignant mesothelial cells. Therefore, he was diagnosed with primary pericardial mesothelioma (PPM) related to asbestos exposure. Although his disease slowly progressed over 18 months, he remained active without any adjuvant treatments such as chemotherapy. Long-term palliation in an aged patient with PPM is rarely obtained using supportive care alone because the prognosis of PPM has been consistently reported to be very poor and almost fatal within a year. Clinical oncologists and thoracic surgeons should be aware of this disease because the accumulation of knowledge on PPM may lead to successful treatment even in aged patients. PMID- 26376727 TI - Evaluation of contaminated drinking water and male breast cancer at Marine Corps Base Camp Lejeune, North Carolina: a case control study. AB - BACKGROUND: Solvents contaminated drinking water supplies at Marine Corps Base Camp Lejeune during 1950s-1985. METHODS: We conducted a case-control study among Marines to evaluate associations between residential exposure to contaminated drinking water at Camp Lejeune and male breast cancer risk. The study included 71 male breast cancer cases and 373 controls identified from the Department of Veteran's Affairs (VA) cancer registry whose military personnel records were available. Controls were selected from cancers not known to be associated with solvent exposure and included 270 skin cancers, 71 mesotheliomas, and 32 bone cancers. Base assignment and risk factor information came from military personnel and VA records. Groundwater contaminant fate/transport and distribution system models provided monthly estimated residential contaminant levels. We conducted exact logistic regression using the 50th percentile level among exposed controls to create low and high exposure categories. We calculated 95% confidence intervals (CIs) to indicate precision of effect estimates. Exploratory analyses used proportional hazards methods to evaluate associations between exposures and age at diagnosis. RESULTS: After adjusting for age at diagnosis, race, and service in Vietnam, the odds ratio (OR) for ever stationed at Camp Lejeune was 1.14 (95% CI: 0.65, 1.97). Adjusted ORs for high residential cumulative exposures to tetrachloroethylene (PCE), t-1,2 dichloroethylene (DCE), and vinyl chloride were 1.20 [95% CI: 0.16-5.89], 1.50 [95% CI: 0.30-6.11], 1.19 [95% CI: 0.16 5.89], respectively, with a monotonic exposure response relationship for PCE only. However these results were based on two or three cases in the high cumulative exposure categories. Ever stationed at Camp Lejeune and high cumulative exposures to trichloroethylene (TCE), PCE, DCE and vinyl chloride were associated with earlier age at onset for male breast cancer; hazard ratios ranged from 1.4-2.7 with wide confidence intervals for cumulative exposure variables. CONCLUSION: Findings suggested possible associations between male breast cancer and being stationed at Camp Lejeune and cumulative exposure to PCE, DCE, and vinyl chloride. TCE, PCE, DCE and vinyl chloride cumulative exposures showed possible associations with earlier age at onset of male breast cancer. However, this study was limited by small numbers of cases in high exposure categories. PMID- 26376728 TI - The relationship between faecal-associated and mucosal-associated microbiota in irritable bowel syndrome patients and healthy subjects. AB - BACKGROUND: The faecal-associated microbiota is commonly seen as a surrogate of the mucosal-associated microbiota. However, previous studies indicate that they are different. Furthermore, analyses of the mucosal microbiota are commonly done after standard bowel cleansing, affecting the microbial composition. AIM: To compare the mucosal-associated microbiota, obtained from unprepared colon, with faecal-associated microbiota in healthy subjects and irritable bowel syndrome (IBS) patients. METHODS: Faecal and mucosal biopsies were obtained from 33 IBS patients and 16 healthy controls. Of IBS patients, 49% belonged to the diarrhoea predominant subgroup and 80% suffered from IBS symptoms during at least 5 years. Biopsies were collected from unprepared sigmoid colon and faecal samples a day before colonoscopy. Microbiota analyses were performed with a phylogenetic microarray and redundancy discriminant analysis. RESULTS: The composition of the mucosal- and the faecal-associated microbiota in unprepared sigmoid colon differs significantly (P = 0.002). Clinical characteristics of IBS did not correlate with this difference. Bacteroidetes dominate the mucosal-associated microbiota. Firmicutes, Actinobacteria and Proteobacteria dominate the faecal-associated microbiota. Healthy subjects had a significantly higher (P < 0.005) abundance (1.9%) of the bacterial group uncultured Clostridiales I in the mucosal associated microbiota than IBS patients (0.3%). Bacterial diversity was higher in faecal- compared with mucosal-associated microbiota in IBS patients (P < 0.005). No differences were found in healthy subjects. CONCLUSIONS: Differences in the mucosal-associated microbiota between healthy individuals and IBS patients are minimal (one bacterial group) compared to differences in the faecal microbiota of both groups (53 bacterial groups). Microbial aberrations characterising IBS are more pronounced in the faeces than in the mucosa. PMID- 26376729 TI - Expression of myostatin in the spotted rose snapper Lutjanus guttatus during larval and juvenile development under cultured conditions. AB - In this study, the developmental expression pattern of myostatin (mstn) in the spotted rose snapper Lutjanus guttatus under culture conditions is presented. The full coding sequence of mstn from L. guttatus was isolated from muscle tissue, obtaining 1134 nucleotides which encode a peptide of 377 amino acids. The phylogenetic analysis indicated that this sequence corresponds to mstn-1. mstn expression was detected in embryonic stages, and maintained at low levels until 28 days post-hatch, when it showed a significant increase, coinciding with the onset of metamorphosis. After that, expression was fluctuating, coinciding probably with periods of rapid and slow muscle growth or individual growth rates. mstn expression was also analysed by body mass with higher levels detected in smaller animals, irrespective of age. mstn was also expressed in other tissues from L. guttatus, presenting higher levels in brain, eye and gill. In brain for instance, two variants of mstn were isolated, both coding sequences were identical to muscle, except that one of them contained a 75 nucleotide deletion in exon 1, maintaining the reading frame but deleting two conserved cysteine residues. Phylogenetic analysis indicated that this brain variant was also mstn 1. The function of this variant is not clear and needs further investigation. These results indicate that mstn-1 participates in different physiological processes other than muscle growth in fishes. PMID- 26376730 TI - Enzymatically Shifting Nitroxides for EPR Spectroscopy and Overhauser-Enhanced Magnetic Resonance Imaging. AB - In vivo investigations of enzymatic processes using non-invasive approaches are a long-lasting challenge. Recently, we showed that Overhauser-enhanced MRI is suitable to such a purpose. A beta-phosphorylated nitroxide substrate prototype exhibiting keto-enol equilibrium upon enzymatic activity has been prepared. Upon enzymatic hydrolysis, a large variation of the phosphorus hyperfine coupling constant (Deltaa(P)=4 G) was observed. The enzymatic activities of several enzymes were conveniently monitored by electronic paramagnetic resonance (EPR). Using a 0.2 T MRI machine, in vitro and in vivo OMRI experiments were successfully performed, affording a 1200% enhanced MRI signal in vitro, and a 600% enhanced signal in vivo. These results highlight the enhanced imaging potential of these nitroxides upon specific enzymatic substrate-to-product conversion. PMID- 26376731 TI - Ruthenium(II)-Catalyzed C-H Functionalizations with Allenes: Versatile Allenylations and Allylations. AB - Ruthenium(II)-catalyzed direct C-H functionalization of aromatic compounds with allenes was achieved under exceedingly mild reaction conditions to yield trisubstituted allenes. The reactions of N-methoxybenzamides proceeded smoothly in an isohypsic fashion at ambient temperature with high chemo- and regioselectivity, thereby providing a versatile means of accessing trisubstituted allenes. Detailed mechanistic studies were suggestive of a kinetically relevant C H metalation step, which occurs by the assistance of a carboxylate moiety; this also set the stage for unprecedented C-H allylations with removable directing groups in a step-economical fashion. PMID- 26376732 TI - Optimization of yeast-based production of medicinal protoberberine alkaloids. AB - BACKGROUND: Protoberberine alkaloids are bioactive molecules abundant in plant preparations for traditional medicines. Yeast engineered to express biosynthetic pathways for fermentative production of these compounds will further enable investigation of the medicinal properties of these molecules and development of alkaloid-based drugs with improved efficacy and safety. Here, we describe the optimization of a biosynthetic pathway in Saccharomyces cerevisiae for conversion of rac-norlaudanosoline to the protoberberine alkaloid (S)-canadine. RESULTS: This yeast strain is engineered to express seven heterologous enzymes, resulting in protoberberine alkaloid production from a simple benzylisoquinoline alkaloid precursor. The seven enzymes include three membrane-bound enzymes: the flavin dependent oxidase berberine bridge enzyme, the cytochrome P450 canadine synthase, and a cytochrome P450 reductase. A number of strategies were implemented to improve flux through the pathway, including enzyme variant screening, genetic copy number variation, and culture optimization, that led to an over 70-fold increase in canadine titer up to 1.8 mg/L. Increased canadine titers enable extension of the pathway to produce berberine, a major constituent of several traditional medicines, for the first time in a microbial host. We also demonstrate that this strain is viable at pilot scale. CONCLUSIONS: By applying metabolic engineering and synthetic biology strategies for increased conversion of simple benzylisoquinoline alkaloids to complex protoberberine alkaloids, this work will facilitate chemoenzymatic synthesis or de novo biosynthesis of these and other high-value compounds using a microbial cell factory. PMID- 26376733 TI - Unusual coexistence of extramedullary plasmacytoma and nasopharyngeal carcinoma in nasopharynx. AB - Nasopharyngeal carcinoma (NPC) is an EBV-associated malignant tumor of nasopharynx. As extremely rare condition, the second primary cancer of nasopharynx can occur in NPC patients synchronously or subsequently. Extramedullary plasmacytoma (EMP) is a rare tumor and commonly originates in the head and neck region. However, there is no report to describe a collision tumor of NPC and EMP occurring in the same nasopharyngeal mass. We report here an unusual case of synchronous coexistence of NPC and EMP occurring in the nasopharynx of an old male patient. A 63-year-old male patient presented with a 3 month history of right-sided nasal obstruction and recently intermittent epistaxis without enlargement of cervical lymph nodes. The solitary mass of nasopharynx was found by radiological and nasopharyngeal examination. Histologically, the mass contained two separated portions and displayed typically histological features of NPC and EMP, respectively. In EMP portion, the tumor was composed of monomorphic plasmacytoid-appearing cells with immuno-positive to CD79a, CD138, CD38, MUM-1 and CD56, but lack immunoreactivity to pan-CK (AE1/AE3), CD20, CD21 and EBERs. In NPC portion, the tumor cells formed irregular shaped islands with diffusely immuno-positive to pan-CK (AE1/AE3), EMA and EBERs, but lack expressions of lymphoplasmacytic markers. A diagnosis of simultaneous occurrence of EMP and NPC in nasopharynx was made. There was no evidence of tumor recurrence or metastasis 18-month follow-up after radiotherapy. To our knowledge, it may be the first case of coexistence of EMP and NPC synchronously. In addition, the histological differential diagnosis and relevant potential mechanism of this unusual collision tumor were also discussed. PMID- 26376734 TI - Licarin A is a candidate compound for the treatment of immediate hypersensitivity via inhibition of rat mast cell line RBL-2H3 cells. AB - OBJECTIVES: We previously demonstrated that some phenylpropanoids are capable of inhibiting activated mast cells. This study evaluated the anti-allergic effects of licarin A, a neolignan isolated from various plants, on antigen-stimulated rat mast cell line. METHODS: The inhibitory effects of licarin A on histamine release, tumour necrosis factor-alpha (TNF-alpha) and prostaglandin D2 (PGD2) production, and cyclooxygenase-2 (COX-2) expression in dinitrophenyl-human serum albumin (DNP-HSA) rat basophilic leukemia cells (DNP-HSA-stimulated RBL-2H3 cells), were investigated by spectrofluorometry, ELISA and immunoblotting. KEY FINDINGS: Licarin A significantly and dose-dependently reduced TNF-alpha production (IC50 12.6 +/- 0.3 MUm) in DNP-HSA-stimulated RBL-2H3 cells. Furthermore, the levels of PGD2 secretion in DNP-HSA-stimulated cells pretreated with licarin A were lower than those stimulated with DNP-HSA alone (positive control). Treatment with licarin A at 20 MUm produced slight suppression of DNP HSA-induced increases in COX-2 mRNA and protein levels. We identified several signalling pathways that mediated these pharmacological effects. Licarin A treatment tended to reduce phosphorylated protein kinase C alpha/beta II (PKCalpha/betaII) and p38 mitogen-activated protein kinase (MAPK) protein levels. CONCLUSIONS: Our results demonstrate that licarin A reduces TNF-alpha and PGD2 secretion via the inhibition of PKCalpha/betaII and p38 MAPK pathways; this compound may be useful for attenuating immediate hypersensitivity. PMID- 26376735 TI - Analysis of the level of general clinical skills of physician assistant students using an objective structured clinical examination. AB - RATIONALE, AIMS AND OBJECTIVES: The physician assistant (PA) is trained to perform clinical tasks traditionally performed by medical doctors (MDs). Previous research showed no difference in the level of clinical skills of PAs compared with MDs in a specific niche, that is the specialty in which they are employed. However, MDs as well as PAs working within a specialty have to be able to recognize medical problems in the full scope of medicine. The objective is to examine PA students' level of general clinical skills across the breadth of clinical cases. METHOD: A cross-sectional study was conducted. PA students and recently graduated MDs in the Netherlands were observed on their clinical skills by means of an objective structured clinical examination comprising five stations with common medical cases. The level of mastering history taking, physical examination, communication and clinical reasoning of PA students and MDs were described in means and standard deviation. Cohen's d was used to present effect sizes. RESULTS: PA students and MDs score about equal on history taking (PA 5.8 +/- 0.8 vs. MD 5.7 +/- 0.7), physical examination (PA 4.8 +/- 1.3 vs. MD 5.4 +/- 0.8) and communication (PA: 8.2 +/- 0.8 vs. MD: 8.6 +/- 0.5) in the full scope of medicine. In the quality of the report, including the patient management plan, PA students scored a mean of 6.0 +/- 0.6 and MDs 6.8 +/- 0.6. CONCLUSIONS: In this setting in the Netherlands, PA students and MDs score about equal in the appraisal of common cases in medical practice. The slightly lower scores of PA students' clinical reasoning in the full scope of clinical care may have raise attention to medical teams working with PAs and PA training programmes. PMID- 26376736 TI - Visual Assessment of Brain Perfusion MRI Scans in Dementia: A Pilot Study. AB - PURPOSE: Functional imaging is becoming increasingly important for the detection of neurodegenerative disorders. Perfusion MRI with arterial spin labeling (ASL) has been reported to provide promising diagnostic possibilities but is not yet widely used in routine clinical work. The aim of this study was to compare, in a clinical setting, the visual assessment of subtracted ASL CBF maps with and without additional smoothing, to FDG-PET data. METHODS: Ten patients with a clinical diagnosis of dementia and 11 age-matched cognitively healthy controls were examined with pseudo-continuous ASL (pCASL) and 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET). Three diagnostic physicians visually assessed the pCASL maps after subtraction only, and after postprocessing using Gaussian smoothing and GLM-based beta estimate functions. The assessment scores were compared to FDG PET values. Furthermore, the ability to discriminate patients from healthy elderly controls was assessed. RESULTS: Smoothing improved the correlation between visually assessed regional ASL perfusion scores and the FDG PET SUV-r values from the corresponding regions. However, subtracted pCASL maps discriminated patients from healthy controls better than smoothed maps. Smoothing increased the number of false-positive patient identifications. Application of beta estimate functions had only a marginal effect. CONCLUSION: Spatial smoothing of ASL images increased false positive results in the discrimination of hypoperfusion conditions from healthy elderly. It also decreased interreader agreement. However, regional characterization and subjective perception of image quality was improved. PMID- 26376737 TI - Evaluation of the bristle end-rounding patterns of children's toothbrushes using scanning electron microscopy and stereomicroscopy. AB - OBJECTIVES: The aim of this study was to evaluate the proportions of end-rounded bristles via observations of the end patterns of various children's toothbrushes with scanning electron microscopy (SEM) and stereomicroscopy. METHODS: Ten different brands of children's toothbrushes were chosen, and tufts from each toothbrush were used. The prepared bristle specimens were observed on SEM and stereomicroscopic images and classified as acceptable (A1-A3) and non-acceptable (N1-N5) according to the modified classification. Then, the proportions of end rounded bristles were calculated. RESULTS: Analyses of the 10 toothbrushes revealed that the proportions of acceptable end-rounded bristles ranged from 1.4% to 20.2% on SEM and from 0.0% to 18.0% on stereomicroscopic examinations. Additionally, some toothbrushes had labels that indicated bristle end-rounding, but the proportions of end-rounded bristles were low. CONCLUSIONS: The types and percentages of bristle ends of children's toothbrushes marketed in Korea were various, but the amount of acceptable end-rounded bristles was low. The result, that even toothbrushes labelled as end-rounded had potential to harm oral tissue, demonstrates that quality control for rounding bristle ends as well as the labelling for end-rounded bristles is needed. PMID- 26376738 TI - Hemoglobin H Disease in Turkey: Experience from Eight Centers. AB - The purpose of this study was to research the problem of hemoglobin H (HbH) disease, to reveal the distribution patterns among different health centers, and to emphasize the importance of this disease for Turkey. A total of 273 patients were included from 8 hemoglobinopathy centers. The Antakya Hemoglobinopathy Center reported 232 patients and the remaining 7 centers reported 41 patients. PubMed was also searched for published articles related to Turkish patients with HbH disease, and we found 16 articles involving a total of 198 HbH patients. Most of the patients were reported from Antakya; thus, special attention should be paid to this region. This is a preliminary study to investigate the extent of the problem of HbH disease and it emphasizes the need for hematology associations or the Ministry of Health to record all cases of HbH disease in Turkey. PMID- 26376739 TI - Wide prevalence of hybridization in two sympatric grasshopper species may be shaped by their relative abundances. AB - BACKGROUND: Hybridization between species is of conservation concern as it might threaten the genetic integrity of species. Anthropogenic factors can alter hybridization dynamics by introducing new potentially hybridizing species or by diminishing barriers to hybridization. This may even affect sympatric species pairs through environmental change, which so far has received little attention. We studied hybridization prevalence and the underlying behavioral mechanisms in two sympatric grasshopper species, a rare specialist (Chorthippus montanus) and a common generalist (Chorthippus parallelus). We conducted a mate choice experiment with constant intraspecific density and varying heterospecific density, i.e. varying relative frequency of both species. RESULTS: Mate choice was frequency dependent in both species with a higher risk of cross-mating with increasing heterospecific frequency, while conspecific mating increased linearly with increasing conspecific density. This illustrates that reproductive barriers could be altered by environmental change, if the relative frequency of species pairs is affected. Moreover, we performed a microsatellite analysis to detect hybridization in twelve syntopic populations (and four allotopic populations). Hybrids were detected in nearly all syntopic populations with hybridization rates reaching up to 8.9 %. Genetic diversity increased for both species when hybrids were included in the data set, but only in the common species a positive correlation between hybridization rate and genetic diversity was detected. CONCLUSION: Our study illustrates that the relative frequency of the two species strongly determines the effectiveness of reproductive barriers and that even the more choosy species (Ch. montanus) may face a higher risk of hybridization if population size decreases and its relative frequency becomes low compared to its sister species. The asymmetric mate preferences of both species may lead to quasi unidirectional gene flow caused by unidirectional backcrossing. This might explain why genetic diversity increased only in the common species, but not in the rare one. Altogether, the hybridization rate was much higher than expected for a widely sympatric species pair. PMID- 26376740 TI - Muscle wasting as main evidence of energy impairment in cancer cachexia: future therapeutic approaches. AB - The present review aimed at discussing the impact, pathogenesis and therapeutic approaches of muscle wasting, which is a major clinical feature of cancer-related cachexia syndrome. The pathogenesis of muscle wasting in cancer cachexia lies in a discrepancy between anabolic and catabolic pathways mediated by chronic inflammation. Effective interventions specifically aimed at hampering muscle loss and enhancing muscle function are still lacking. Promising agents include anti inflammatory, orexigenic and anabolic drugs, alongside with nutritional supplements that influence the STAT3 and PI3K/Akt/mTOR pathways involved in muscle wasting. Personalized physical activity combined with pharmacological and nutritional support hold promise. A greater understanding of the pathogenetic processes of cancer cachexia-related muscle wasting will enable the development of an early and effective targeted mechanism-based multimodal approach. PMID- 26376741 TI - Immunotherapy of Brain Tumors. AB - Glioma is one of the most devastating cancers, affecting children and young adults, and associated with a very high morbidity and poor prognosis. The propensity of glioma cells to invade normal brain structures makes current treatments poorly efficient and new therapeutic strategies an urgent need. We now know that many of the rules governing immune responses in other tissues are also valid for the brain, providing solid scientific background for developing new strategies exploiting the immune system to fight brain tumors. Some vaccines use tumor-specific mutated peptides (EGFRvIII, IDH1 or personalized peptides), but most are tumor-associated or undefined tumor-derived peptides (tumor-eluted peptides, peptides predicted from tumor-associated proteins or bound to HSPPC-96 complexes), in some cases pulsed on dendritic cells. Cell therapy is less advanced but the first clinical trials exploring the safety of T cells with chimeric antigen receptors incorporating antibodies to EGFRvIII, IL-13Ralpha2 or Her2 are ongoing. Finally, various strategies designed at reshaping the glioma microenvironment are being tested, including TGFbeta inhibition, Treg depletion and immune checkpoint blockade. Altogether, combining vaccines, cell therapy and reshaping of the tumor microenvironment will be the foundation for a new era of therapeutics for brain tumors. PMID- 26376742 TI - Functional analysis of the aefR mutation and identification of its binding site in Pseudomonas syringae pv. tabaci 11528. AB - The TetR family transcriptional regulator AefR contributes to the regulation of the quorum-sensing system. However, the role of AefR in the regulatory network of the phytopathogen Pseudomonas syringae pathovars is not known. In this study, the phenotype of a P. syringae pv. tabaci 11528 aefR deletion mutant strain was examined. The aefR gene expression and AefR DNA-binding affinity were examined by quantitative real-time polymerase chain reaction and electrophoretic mobility shift assay, respectively. AefR was found to control quorum-sensing genes as well as the efflux genes mexE, mexF, and oprN via an indirect mechanism. AefR binds to its own operator site as well as to the palindromic sequence between positions 28 and -2 corresponding to the transcription start site of aefR, as determined by dye primer sequencing. These results suggest that P. syringae AefR modulates quorum sensing and efflux as well as its own expression, which can be exploited by strategies developed to manage this plant parasite. PMID- 26376743 TI - A more reliable measurement method for metal/graphene contact resistance. AB - The contact resistance of metal/graphene is becoming a major limiting factor for graphene devices. Among various kinds of contact resistance test methods, the transmission line model is the most common approach to extract contact resistance in graphene devices. However, experiments show that in some cases there exists large inaccuracy and instability using this method. In this study, we added a cross-bridge structure at the terminal of the transmission line as a supporting test. This modified transmission line measurement structure can easily compare not only the transmission line and Kelvin contact resistance, getting a more reliable value, but also the other contact-related parameters, such as specific contact resistivity, transfer length and the graphene sheet resistance under and outside contact metal at the same time. The new measurement test is very helpful in enabling us to study the contact property accurately. The specific contact resistivity in our experiment is in the range of 2.0 * 10(-6) Omega . cm(2) and 3.0 * 10(-6) Omega . cm(2) at room temperature. With the temperature decreasing from 290 K to 60 K, the transfer length fluctuates around 1.7 MUm, and the specific contact resistivity reduces to less than 2.0 * 10(-6) Omega . cm(2). PMID- 26376744 TI - Acute viral hepatitis presenting as cytomegalovirus, hepatitis E and Epstein-Barr virus IgM antibody positive. AB - We report a case of acute cytomegalovirus (CMV) infection with positive HEV and Epstein-Barr virus (EBV) serology. No patients have been reported positive for immunoglobulin (Ig)M antibodies to all three viruses. This patient had progressively increasing titres of IgM antibody for CMV, HEV and EBV. Only CMV DNA was detectable before antiviral treatment. After antiviral treatment, the patient recovered completely. At day 180 the CMV IgG test had converted to positive with CMV IgM (+), EBV IgM (-) and HEV IgM (-). Our report indicates that dependence upon serology alone is unreliable in the diagnosis of acute CMV, EBV and HEV infections. The diagnosis of CMV, HEV and EBV should be based on a combination of clinical features, serology and confirmatory PCR testing. PMID- 26376745 TI - Prevalence, outcomes and factors associated with adult in hospital cardiac arrests in a low-income country tertiary hospital: a prospective observational study. AB - BACKGROUND: Research on cardiac arrest and cardiopulmonary resuscitation (CPR) has considerably increased in recent decades, and international guidelines for resuscitation have been implemented and have undergone several changes. Very little is known about the prevalence and management of in-hospital cardiac arrest in low-resource settings. We therefore sought to determine the prevalence, outcomes and associated factors of adult inpatients with cardiac arrest at a tertiary referral hospital in a low-income country. METHODS: Upon obtaining institutional approval, we conducted a prospective observational period prevalence study over a 2-month period. We recruited adult inpatients with cardiac arrest in the intensive care unit and emergency wards of Mulago Hospital, Uganda during the study period. We reviewed all files and monitoring charts, and also any postmortem findings. Data were analyzed with Stata 12 and statistical significance was set at p < 0.05. RESULTS: There was a cardiac arrest in 2.3% (190) of 8,131 hospital admissions; 34.5% occurred in the intensive care unit, 4.4% in emergency operating theaters, and 3.0% in emergency wards. A majority (63.2%) was unwitnessed, and only 35 patients (18.4%) received CPR. There was return of spontaneous circulation (ROSC) in 14 (7.4%) cardiac arrest patients. Survival to 24 h occurred in three ROSC patients, which was only 1.6% of all cardiac arrest patients during the study period. Trauma was the most common primary diagnosis and HIV infection was the most common co-morbidity. CONCLUSION: Our hospital has a high prevalence of cardiac arrest, and low rates of CPR performance, ROSC, and 24-hour survival. Single provider CPR; abnormal temperatures as well as after hours/weekend CAs were associated with lower survival rates. PMID- 26376746 TI - Lupus vulgaris mimicking hemangioma diagnosed 42 years after onset: a case report. AB - INTRODUCTION: Lupus vulgaris is the most common form of cutaneous tuberculosis. It may easily be overlooked if a proper differential diagnosis is omitted. CASE PRESENTATION: A 46-year-old Turkish woman presented with a 42-year history of erythamatous plaque on her left arm. Ziehl-Neelsen and periodic acid-Schiff stains did not show any acid-fast bacilli. Culture from a biopsy specimen was negative for Mycobacterium tuberculosis. The result of a polymerase chain reaction-based assay for Mycobacterium was negative. Histopathologic findings revealed a tuberculoid granuloma containing epithelioid cells, lymphocytes and Langerhans-type giant cells. A diagnosis of lupus vulgaris was made by clinical and histopathologic findings. CONCLUSIONS: The lesion improved after antituberculous therapy, confirming the diagnosis of lupus vulgaris. PMID- 26376748 TI - Erratum to: Evaluating the efficacy of a web-based self-help intervention with and without chat counseling in reducing the cocaine use of problematic cocaine users: the study protocol of a pragmatic three-arm randomized controlled trial. PMID- 26376747 TI - Somatic mosaicism for copy-neutral loss of heterozygosity and DNA copy number variations in the human genome. AB - BACKGROUND: Somatic mosaicism denotes the presence of genetically distinct populations of somatic cells in one individual who has developed from a single fertilised oocyte. Mosaicism may result from a mutation that occurs during postzygotic development and is propagated to only a subset of the adult cells. Our aim was to investigate both somatic mosaicism for copy-neutral loss of heterozygosity (cn-LOH) events and DNA copy number variations (CNVs) in fully differentiated tissues. RESULTS: We studied panels of tissue samples (11-12 tissues per individual) from four autopsy subjects using high-resolution Illumina HumanOmniExpress-12 BeadChips to reveal the presence of possible intra-individual tissue-specific cn-LOH and CNV patterns. We detected five mosaic cn-LOH regions >5 Mb in some tissue samples in three out of four individuals. We also detected three CNVs that affected only a portion of the tissues studied in one out of four individuals. These three somatic CNVs range from 123 to 796 kb and are also found in the general population. An attempt was made to explain the succession of genomic events that led to the observed somatic genetic mosaicism under the assumption that the specific mosaic patterns of CNV and cn-LOH changes reflect their formation during the postzygotic embryonic development of germinal layers and organ systems. CONCLUSIONS: Our results give further support to the idea that somatic mosaicism for CNVs, and also cn-LOHs, is a common phenomenon in phenotypically normal humans. Thus, the examination of only a single tissue might not provide enough information to diagnose potentially deleterious CNVs within an individual. During routine CNV and cn-LOH analysis, DNA derived from a buccal swab can be used in addition to blood DNA to get information about the CNV/cn-LOH content in tissues of both mesodermal and ectodermal origin. Currently, the real frequency and possible phenotypic consequences of both CNVs and cn-LOHs that display somatic mosaicism remain largely unknown. To answer these questions, future studies should involve larger cohorts of individuals and a range of tissues. PMID- 26376749 TI - Effect of Tumor Necrosis Factor-Alpha on Erythropoietin and Erythropoietin Receptor-Induced Erythroid Progenitor Cell Proliferation in beta Thalassemia/Hemoglobin E Patients. AB - OBJECTIVE: Thalassemia is one of the genetic diseases that cause anemia and ineffective erythropoiesis. Increased levels of several inflammatory cytokines have been reported in beta-thalassemia and might contribute to ineffective erythropoiesis. However, the mechanism by which tumor necrosis factor-alpha (TNF alpha) is involved in ineffective erythropoiesis in thalassemic patients remains unclear. The objective of this study is to investigate the effect of TNF-alpha on the erythropoietin (EPO) and erythropoietin receptor (EPOR) expression involved in proliferation of beta-thalassemia/hemoglobin (Hb) E erythroid progenitor cells compared with cells from healthy subjects. MATERIALS AND METHODS: CD34-positive cells were isolated from heparinized blood by using the EasySep(r) CD34 selection kit. Cells were then cultured with suitable culture medium in various concentrations of EPO for 14 days. The effect of TNF-alpha on percent cell viability was analyzed by trypan blue staining. In addition, the percentage of apoptosis and levels of EPOR protein were measured by flow cytometry. RESULTS: Upon EPO treatment, a higher cell number was observed for erythroid progenitor cells from both healthy participants and beta-thalassemia/Hb E patients. However, a reduction of apoptosis was found in EPO-treated cells especially for beta thalassemia/Hb E patients. Interestingly, TNF-alpha caused higher levels of cell apoptosis and lower levels of EPOR protein in thalassemic erythroid progenitor cells. CONCLUSION: TNF-alpha caused a reduction in the level of EPOR protein and EPO-induced erythroid progenitor cell proliferation. It is possible that TNF alpha could be involved in the mechanism of ineffective erythropoiesis in beta thalassemia/Hb E patients. PMID- 26376750 TI - Enzyme-free and DNA-based multiplexer and demultiplexer. AB - A DNA-based 2:1 multiplexer and 1:2 demultiplexer have been conceptually realized in enzyme-free conditions. For the first time, the designed DNA-based multiplexer could be implemented by keeping input/output signal homogeneity, which has great potential application in information processing. PMID- 26376751 TI - Reinforced Poly(Propylene Carbonate) Composite with Enhanced and Tunable Characteristics, an Alternative for Poly(lactic Acid). AB - The acidic nature of the degradation products of polyesters often leads to unpredictable clinical complications, such as necrosis of host tissues and massive immune cell invasions. In this study, poly(propylene carbonate) (PPC) and starch composite is introduced with superior characteristics as an alternative to polyester-based polymers. The degradation products of PPC-starch composites are mainly carbon dioxide and water; hence, the associated risks to the acidic degradation of polyesters are minimized. Moreover, the compression strength of PPC-starch composites can be tuned over the range of 0.2+/-0.03 MPa to 33.9+/ 1.51 MPa by changing the starch contents of composites to address different clinical needs. More importantly, the addition of 50 wt % starch enhances the thermal processing capacity of the composites by elevating their decomposition temperature from 245 to 276 degrees C. Therefore, thermal processing methods, such as extrusion and hot melt compression methods can be used to generate different shapes and structures from PPC-starch composites. We also demonstrated the cytocompatibility and biocompatibility of these composites by conducting in vitro and in vivo tests. For instance, the numbers of osteoblast cells were increased 2.5 fold after 7 days post culture. In addition, PPC composites in subcutaneous mice model resulted in mild inflammatory responses (e.g., the formation of fibrotic tissue) that were diminished from two to 4 weeks postimplantation. The long-term in vivo biodegradation of PPC composites are compared with poly(lactic acid) (PLA). The histochemical analysis revealed that after 8 weeks, the biodegradation of PLA leads to massive immune cell infusion and inflammation at the site, whereas the PPC composites are well-tolerated in vivo. All these results underline the favorable properties of PPC-starch composites as a benign biodegradable biomaterial for fabrication of biomedical implants. PMID- 26376752 TI - All in the Blood: A Review of Aboriginal Australians' Cultural Beliefs About Blood and Implications for Biospecimen Research. AB - Public participation in medical research and biobanking is considered key to advances in scientific discovery and translation to improved health care. Cultural concerns relating to blood have been found to affect the participation of indigenous peoples and minorities in research, but such concerns are rarely specified in the literature. This article presents a review of the role of blood in Australian Aboriginal cultures. We discuss the range of meanings and uses of blood in traditional culture, including their use in ceremonies, healing, and sorcery. We draw on more recent literature on Aboriginal Australians and biomedicine to consider how traditional beliefs may be changing over time. These findings provide an empirical basis for researchers and bioethicists to develop culturally grounded strategies to boost the participation of Aboriginal Australians in biomedical research. They also serve as a model for integrating anthropological literature with bioethical concerns that could be applied to other indigenous and minority groups. PMID- 26376753 TI - Participant Satisfaction With a Preference-Setting Tool for the Return of Individual Research Results in Pediatric Genomic Research. AB - The perceived benefit of return of individual research results (IRRs) in accordance to participants' preferences in genomic biobank research is unclear. We developed an online preference-setting tool for return of IRRs based on the preventability and severity of a condition, which included an opt-out option for IRRs for mental illness, developmental disorders, childhood-onset degenerative conditions, and adult-onset conditions. Parents of patients <18 years of age at Boston Children's Hospital were randomized to the hypothetical scenario that their child was enrolled in one of four biobanks with different policies for IRRs to receive (a) "None," (b) "All," (c) "Binary"--choice to receive all or none, and (d) "Granular"--use the preference-setting tool to choose categories of IRRs. Parents were given a hypothetical IRRs report for their child. The survey was sent to 11,391 parents and completed by 2,718. The Granular group was the most satisfied with the process, biobank, and hypothetical IRRs received. The None group was least satisfied and least likely to agree that the biobank was beneficial (p < .001). The response to the statement that the biobank was harmful was not different between groups. Our data suggest that the ability to designate preferences leads to greater satisfaction and may increase biobank participation. PMID- 26376755 TI - A four-unit [c2]daisy chain connected by hydrogen bonds. AB - A mono-adenine-functionalized pillar[5]arene and a guest including uracil were prepared. They formed a novel four-unit [c2]daisy chain both in the solid state and in a chloroform solution. As far as we know, this [c2]daisy chain is the first one without a covalently bound linear thread. This unique assembly behavior is mainly induced by hydrogen-bond interactions between A and U in the A-U base pairs. PMID- 26376756 TI - A novel chiral phase of achiral hard triangles and an entropy-driven demixing of enantiomers. AB - We investigate the phase behavior of a system of hard equilateral and right angled triangles in two dimensions using Monte Carlo simulations. Hard equilateral triangles undergo a continuous isotropic-triatic liquid crystal phase transition at packing fraction phi = 0.7. Similarly, hard right-angled isosceles triangles exhibit a first-order phase transition from an isotropic fluid phase to a rhombic liquid crystal phase with a coexistence region phi ? [0.733, 0.782]. Both these liquid crystals undergo a continuous phase transition to their respective close-packed crystal structures at high pressures. Although the particles and their close-packed crystals are both achiral, the solid phases of equilateral and right-angled triangles exhibit spontaneous chiral symmetry breaking at sufficiently high packing fractions. The colloidal triangles rotate either in the clockwise or anti-clockwise direction with respect to one of the lattice vectors for packing fractions higher than phichi. As a consequence, these triangles spontaneously form a regular lattice of left- or right-handed chiral holes which are surrounded by six triangles in the case of equilateral triangles and four or eight triangles for right-angled triangles. Moreover, our simulations show a spontaneous entropy-driven demixing transition of the right- and left handed "enantiomers". PMID- 26376758 TI - Reduction in early mortality outcomes after bariatric surgery in France between 2007 and 2012: A nationwide study of 133,000 obese patients. AB - BACKGROUND: Early postoperative mortality after bariatric surgery has been reported in large national studies before sleeve gastrectomy (SG) was introduced as a stand-alone procedure. The aim of this study was to investigate the 90-day postoperative mortality rates after bariatric surgery in France on a nationwide basis. METHODS: All morbidly obese patients who underwent adjustable gastric banding (AGB), gastric bypass (GBP), or SG in France between 2007 and 2012 were included in this study. Multivariate analyses were conducted using the French National Health Service Database data to ascertain predictive factors for 90-day postoperative mortality. RESULTS: Data from 133,804 patients were analyzed. SG was performed in 36.5% of cases, GBP in 31.2%, AGB in 32.3%, and revisional surgery in 5.1%. The postoperative mortality rate (POM) for the 3 procedures was 0.12%. The rate of POM remained stable for AGB (0.01%), and it decreased from 0.25 to 0.08% and from 0.36 to 0.11% for SG and GBP, respectively. POM was greater among male patients and was associated with age, type-2 diabetes, high blood pressure, body mass index, open surgery, and hospital procedural volume. CONCLUSION: The rate of early mortality after bariatric surgery was low, and has decreased greatly during the past few years. AGB presents a mortality rate close to nil and SG has a risk of early mortality that is about half that of GBP. PMID- 26376757 TI - Milk fat globule-epidermal growth factor-factor VIII downregulates interleukin-17 expression in sepsis by modulating STAT3 activation. AB - BACKGROUND: Milk fat globule-epidermal growth factor-factor VIII (MFG-E8) is a secretory glycoprotein with a known role in inflammation. In sepsis, interleukin (IL)-17 acts as a proinflammatory cytokine to exaggerate systemic inflammation. We hypothesize that MFG-E8 downregulates IL-17 expression in sepsis. METHODS: Sepsis was induced in 8-week-old male C57BL/6 mice by cecal ligation and puncture (CLP). Recombinant mouse MFG-E8 (rmMFG-E8) at a dosage of 20 MUg/kg body weight or phosphate-buffered saline was concurrently injected. After 10 hours, blood and spleen samples were harvested for analysis. For in vitro studies, splenocytes isolated from healthy mice pretreated with rmMFG-E8 and splenocytes from MFG-E8 knockout (mfge8(-/-)) mice were stimulated with phorbol 12-myristate 13-acetate (PMA) and ionomycin, followed by measurement of IL-17 expression with either quantitative PCR or enzyme-linked immunosorbent assay. RESULTS: At 10 hours after CLP, rmMFG-E8 inhibited the elevated levels of IL-17 protein in serum by 31%, compared with the vehicle. In the spleen, rmMFG-E8 reduced the upregulated IL-17 mRNA and protein levels by 81% and 51%, respectively. This correlated with a significant reduction in organ injury markers AST and ALT in sepsis after administration of rmMFG-E8. In vitro treatment of splenocytes isolated from healthy mice with rmMFG-E8 showed significant downregulation in PMA/ionomycin induced IL-17 expression. In contrast, CD4 T-cells from mfge8(-/-) mice showed significant upregulation of IL-17 compared with wild-type mice. The phosphorylated level of signal transducer and activator of transcription 3 (STAT3) was downregulated in spleen tissue of septic mice treated with rmMFG-E8. Conversely, mfge8(-/-) mice showed increased phosphorylated STAT3 compared with wild-type mice after sepsis. CONCLUSION: Our findings demonstrate MFG-E8-mediated downregulation of IL-17 expression, implicating its potential as a novel therapeutic agent against sepsis. PMID- 26376759 TI - Parahydrogen enhanced NMR reveals correlations in selective hydrogenation of triple bonds over supported Pt catalyst. AB - Parahydrogen induced polarization using heterogeneous catalysis can produce impurity-free hyperpolarized gases and liquids, but the comparatively low signal enhancements and limited scope of substrates that can be polarized pose significant challenges to this approach. This study explores the surface processes affecting the disposition of the bilinear spin order derived from parahydrogen in the hydrogenation of propyne over TiO2-supported Pt nanoparticles. The hyperpolarized adducts formed at low magnetic field are adiabatically transported to high field for analysis by proton NMR spectroscopy at 400 MHz. For the first time, the stereoselectivity of pairwise addition to propyne is measured as a function of reaction conditions. The correlation between partial reduction selectivity and stereoselectivity of pairwise addition is revealed. The systematic trends are rationalized in terms of a hybrid mechanism incorporating non-traditional concerted addition steps and well-established reversible step-wise addition involving the formation of a surface bound 2-propyl intermediate. PMID- 26376760 TI - Endothelial Cells, Ankaferd Hemostat, and Estradiol. PMID- 26376761 TI - Structure elucidation of an unusual new sesquiterpene lactone glucoside ester from Crepis pannonica. PMID- 26376762 TI - Metformin prevents DMH-induced colorectal cancer in diabetic rats by reversing the warburg effect. AB - Epidemiologic studies have shown that the treatment of diabetics with metformin reduced the risk of cancer-related mortality. Here, we investigated the chemopreventive effects of metformin on dimethylhydrazine (DMH)-induced colorectal carcinogenesis in diabetic SD rats following metformin treatment and the effect on Warburg effect involved in this process. Diabetic rat models were induced with high-fat feeding in combination with a low dose of Streptozotocin (STZ) and then induce colorectal cancer with a low dose of DMH. The formation of colorectal Aberrant crypt foci (ACF) and the incidence, number and size of the tumor were measured. The proliferation indices of colonic tissues were determined through Proliferating cell nuclear antigen (PCNA) immunostaining. Then detect the expression of PK and IDH in colonic tissues using immunohistochemistry and Western blot. The enzyme activities of HK and PDH in colonic tissues were measured. The growth and expression of PK and IDH and activity of HK and PDH in cell lines LoVo and HT-29 were measured after metformin treatment. The results showed that metformin treatment significantly inhibited the formation of ACF and tumors. The proliferation index of colonic tissues was significantly decreased following metformin treatment. In addition, metformin inhibited cell growth and decreased the imbalance in the expression of the enzymes involved in glycolysis and the TCA cycle. These findings suggested that metformin might produce a synergistic colon cancer-preventative effect in diabetic patients through the regulation of the enzymes expression involved in glucose metabolism. PMID- 26376764 TI - A phase of transition for JPOG. PMID- 26376763 TI - Search for aflatoxin and trichothecene production inhibitors and analysis of their modes of action. AB - Mycotoxin contamination of crops is a serious problem throughout the world because of its impact on human and animal health as well as economy. Inhibitors of mycotoxin production are useful not only for developing effective methods to prevent mycotoxin contamination, but also for investigating the molecular mechanisms of secondary metabolite production by fungi. We have been searching for mycotoxin production inhibitors among natural products and investigating their modes of action. In this article, we review aflatoxin and trichothecene production inhibitors, including our works on blasticidin S, methyl syringate, cyclo(L-Ala-L-Pro), respiration inhibitors, and precocene II. PMID- 26376765 TI - Risk factors for central line-associated bloodstream infection in patients with major burns and the efficacy of the topical application of mupirocin at the central venous catheter exit site. AB - AIM: The aim of this study was to evaluate the efficacy of the topical administration of mupirocin and other practices in central venous catheter (CVC) care to prevent central line-associated bloodstream infections (CLABSI) in patients with major burns. METHODS: Patients with major burns admitted to a burn ICU were divided into four groups and disinfected at the CVC exit site with single povidone iodine (PVP-I) or PVP-I plus topical mupirocin ointment three times a day or once a day, respectively. The bacterial colonization of the skin at the CVC exit site and CVC tips and the incidence of CLABSI were recorded, and the risk factors were analyzed. RESULTS: Administering mupirocin (RR=0.316, p=0.001), increasing the frequency of insertion-site care (RR=0.604, p=0.008), and avoiding cannulation at the burn site (RR=0.148, p<0.001) reduced skin colonization at the CVC insertion site. Topical administration of mupirocin significantly reduces both the bacterial colonization rate at CVC tips (RR=0.316, p=0.001) and the incidence of CLABSI (5.3 vs. 29.1 per 1000 catheter days, p<0.001). CONCLUSIONS: Mupirocin is effective in the prophylaxis of CLABSI. Other CVC care practices were also found to affect the level of bacterial colonization, but their efficacy in preventing CLABSI needs to be evaluated further. PMID- 26376767 TI - Novel phosphorus doped carbon nitride modified TiO2 nanotube arrays with improved photoelectrochemical performance. AB - Novel phosphorus-doped graphitic-carbon nitride (P-C3N4) modified vertically aligned TiO2 nanotube arrays (NTs) were designed and synthesized. They can significantly enhance the conduction and utilization of photogenerated charge carriers of TiO2 NTs. The heterostructure was successfully fabricated through a three-step process: electrochemical anodization and wet-dipping followed by thermal polymerization. The prepared P-C3N4/TiO2 NTs exhibit enhanced light absorption characteristics and improved charge separation and transfer ability, thus resulting in a 3-fold photocurrent (1.98 mA cm(-2) at 0 V vs. Ag/AgCl) compared with that of pure TiO2 NTs (0.66 mA cm(-2) at 0 V vs. Ag/AgCl) in 1 M NaOH solution. The prepared P-C3N4/TiO2 NT photoelectrodes also present excellent photocatalytic and photoelectrocatalytic capabilities in the degradation of methylene blue (MB). The kinetic rate of P-C3N4/TiO2 NTs in the photoelectrocatalytic process for MB is 2.7 times that of pristine TiO2 NTs. Furthermore, the prepared sample was used as a photoanode for solar-driven water splitting, giving a H2 evolution rate of 36.6 MUmol h(-1) cm(-2) at 1.0 V vs. RHE under simulated solar light illumination. This novel structure with a rational design for a visible light response shows potential for metal free materials in photoelectrochemical applications. PMID- 26376766 TI - Associations between body mass index and maternal weight gain on the delivery of LGA infants in Chinese women with gestational diabetes mellitus. AB - BACKGROUND: Women with gestational diabetes mellitus (GDM) are at increased risk for maternal and fetal complications including delivery of large for gestational age (LGA) infants. Maternal body mass index (BMI) and excessive weight gain during pregnancy are associated with delivery of LGA infants. However, whether maternal BMI and weight gain are associated with LGA infants in women with GDM is unclear. BASIC PROCEDURES: Data on 1049 pregnant women who developed GDM were collected from a university teaching hospital in China and retrospectively analyzed. Data included maternal BMI, weight gain, incidence of LGA and gestational week at diagnosis. MAIN FINDINGS: The incidence of LGA infants was significantly associated with maternal BMI (p=0.0002) in women with GDM. The odds of delivery of LGA for obese or overweight pregnant women are 3.8 or 2 times more than normal weight pregnant women. The incidence of LGA infants was also significantly associated with maternal weight gain in women with GDM. The odds ratio of delivery of LGA for pregnant women with excessive weight gain was 3.3 times more than pregnant women with normal weight gain. The effect of weight gain was not significantly different between different maternal BMI. PRINCIPAL CONCLUSION: The incidence of delivery of LGA infants in Chinese women with GDM who were overweight or obese is higher than Caucasians, Hispanic, and Asian Americans. The effects of maternal BMI and weight gain on the delivery of LGA infants by women with GDM are additive. PMID- 26376768 TI - Investigation of DOTA-Metal Chelation Effects on the Chemical Shift of (129) Xe. AB - Recent work has shown that xenon chemical shifts in cryptophane-cage sensors are affected when tethered chelators bind to metals. Here, we explore the xenon shifts in response to a wide range of metal ions binding to diastereomeric forms of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) linked to cryptophane-A. The shifts induced by the binding of Ca(2+) , Cu(2+) , Ce(3+) , Zn(2+) , Cd(2+) , Ni(2+) , Co(2+) , Cr(2+) , Fe(3+) , and Hg(2+) are distinct. In addition, the different responses of the diastereomers for the same metal ion indicate that shifts are affected by partial folding with a correlation between the expected coordination number of the metal in the DOTA complex and the chemical shift of (129) Xe. These sensors may be used to detect and quantify many important metal ions, and a better understanding of the basis for the induced shifts could enhance future designs. PMID- 26376769 TI - Polyhydrogenated Graphene: Excited State Dynamics in Photo- and Electroactive Two Dimensional Domains. AB - Understanding the phenomenon of intense photoluminescence in carbon materials such as hydrogenated graphene, graphene nanoribbons, and so forth is at the forefront of investigations. In this study, six different types of hydrogenated graphene (phG) produced from different starting materials were fully characterized in terms of structure and optical spectroscopy. Comprehensive photoluminescence lifetime analyses of phGs were conducted by combining time correlated single-photon counting with steady-state fluorescence spectroscopy and femtosecond transient absorption spectroscopy. The conclusion drawn from these assays is that graphene islands with diameters in the range from 1.1 to 1.75 nm reveal band gap photoluminescence between 450 and 800 nm. As a complement, phGs were implemented in hybrids with water-soluble electron accepting perylenediimides (PDIs). By virtue of mutual pi-stacking and charge transfer interactions with graphene islands, PDIs assisted in stabilizing aqueous dispersion of phG. Implicit in these ground state interactions is the formation of 300 ps lived charge separated states once photoexcited. PMID- 26376770 TI - Association of Calpain (CAPN) 10 (UCSNP-43, rs3792267) gene polymorphism with elevated serum androgens in young women with the most severe phenotype of polycystic ovary syndrome (PCOS). AB - OBJECTIVES: To highlight a possible association of Calpain (CAPN 10) gene UCSNP 43 polymorphism with hormonal and metabolic traits of young women with different phenotypes of polycystic ovary syndrome (PCOS). DESIGN: PCOS women were genotyped for the CAPN 10 gene UCSNP-43 polymorphism. A comparison of clinical and biochemical features of women with PCOS stratified on the basis of the CAPN 10 gene UCSNP-43 variants was assessed. METHODS: Anthropometric, hormonal and biochemical measurements were carried out in 668 PCOS women and 200 healthy controls. Subjects were also genotyped for the CAPN 10 gene UCSNP-43 polymorphism. The genotype frequency distributions between groups and controls were compared using the chi-square test. The association of the polymorphism with the clinical and biochemical features of the study cohort was estimated as well. RESULTS: No association of the frequency of CAPN 10 gene UCSNP-43 polymorphism with PCOS was detected. No association of the polymorphism with the anthropometric, biochemical and hormonal features was detected both in PCOS and control women. The polymorphism was associated with serum Delta4 androstenedione (p = 0.018), as well as with 17-OH progesterone (17-hydroxyprogesterone) among women with PCOS phenotype A (p = 0.012). CONCLUSIONS: CAPN 10 gene polymorphism UCSNP-43 is deprived of a metabolic contribution to cardiovascular disease (CVD). However, due to its association with androgen excess in phenotype A, CAPN 10 gene polymorphism UCSNP-43 could be used as a genetic marker for CVD in young PCOS women. PMID- 26376771 TI - Aortic Outflow Graft Stenting in Patient With Left Ventricular Assist Device Outflow Graft Thrombosis. PMID- 26376772 TI - Tracking the startle response of guppies Poecilia reticulata in three dimensions. AB - A three-dimensional analysis of startle behaviours of guppies Poecilia reticulata, in dyads or alone, from two populations that show distinct differences in shoaling behaviour was performed. During the first few seconds after a startling stimulus, changes in behaviour, which could be critical if an individual is to survive a predatory attack, and the interactions between pairs of P. reticulata were examined. The enhanced social interactions immediately after the stimulus, as a proxy for shoaling behaviour, and their dissipation were quantified. Social (individuals tested in dyads) v. asocial (tested alone) responses to the startling stimulus were also compared. The three-dimensional reconstruction, from a two-camera, high-frame-rate tracking system allowed for the tracking of the individuals' speed and speed recovery and, for P. reticulata in dyads, interindividual distance and orientation. For the dyads from the high predation population, the closer the individuals were to each other, the more likely they were to be parallel, but no correlation was found for the low predation P. reticulata. The startle response of P. reticulata comprised the following sequence: freezing, darting and skittering and recovery to pre-stimulus swimming behaviour. Upon repeated encounters with the stimulus, a reduced shoaling and startle response was observed, although the rate of reduction was faster in P. reticulata from the high-predation population than those from the low-predation population. The results are discussed in light of what is known about the anti-predator behaviour of this species. PMID- 26376773 TI - Morphology-Controlled Synthesis of Organometal Halide Perovskite Inverse Opals. AB - The booming development of organometal halide perovskites in recent years has prompted the exploration of morphology-control strategies to improve their performance in photovoltaic, photonic, and optoelectronic applications. However, the preparation of organometal halide perovskites with high hierarchical architecture is still highly challenging and a general morphology-control method for various organometal halide perovskites has not been achieved. A mild and scalable method to prepare organometal halide perovskites in inverse opal morphology is presented that uses a polystyrene-based artificial opal as hard template. Our method is flexible and compatible with different halides and organic ammonium compositions. Thus, the perovskite inverse opal maintains the advantage of straightforward structure and band gap engineering. Furthermore, optoelectronic investigations reveal that morphology exerted influence on the conducting nature of organometal halide perovskites. PMID- 26376774 TI - Copper-Catalyzed Oxyboration of Unactivated Alkenes. AB - The first regiodivergent oxyboration of unactivated terminal alkenes is reported, using copper alkoxide as a catalyst, bis(pinacolato)diboron [(Bpin)2 ] as a boron source, and (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) as an oxygen source. The reaction is compatible with various functional groups. Two regioisomers are selectively produced by selecting the appropriate ligands on copper. The products may be used as a linchpin precursor for various other functionalizations, and net processes such as carbooxygenation, aminooxygenation, and dioxygenation of alkenes can be achieved after C-B bond transformations. Mechanistic studies indicate that the reaction involves the following steps: 1) Transmetalation between CuOtBu and (Bpin)2 to generate a borylcopper species; 2) regiodivergent borylcupration of alkenes; 3) oxidation of the thus-generated C-Cu bond to give an alkyl radical; 4) trapping of the resulting alkyl radical by TEMPO. PMID- 26376775 TI - Risk factors for myopia in a discordant monozygotic twin study. AB - PURPOSE: Monozygotic (MZ) twin pairs discordant for disease allow careful examination of environmental factors whilst controlling for genetic variation. The purpose of this study was to examine differences in environmental risk factors in MZ twins discordant for myopia. METHODS: Sixty four MZ twin pairs discordant for refractive error were interviewed. Discordant twins were selected from 1326 MZ twin pairs from the TwinsUK adult twin registry with non-cycloplegic autorefraction. Discordancy was defined as >= 2 Dioptres (D) difference in spherical equivalent (SphE) and discordant for class of refractive error. In a 35 item telephone questionnaire twins were separately asked (and scored) about the risk factors urban/rural residence, occupational status and highest educational level. They responded with more (1), less (-1) or the same (0) as their twin on time spent outside, playing outdoor sport, and on close work aged <16 and 16-25 years. The lower SphE twin's score was subtracted from the higher SphE twin's score, and mean values of the difference calculated for each variable. RESULTS: Sixty four twin pairs were included (mean age 56, range 30-79 years; mean difference in refraction 3.35 D, S.D. 1.55 D, median difference 2.78 D). Within discordant MZ twin pairs, the more myopic twin was associated with having a higher occupational status (mean score between 16 and 25 years -0.11; 95% CI 0.19 to -0.04; mean score aged >25 years -0.23, 95% CI -0.28 to -0.17), being resident in urban area (mean score -0.26; 95% CI -0.33 to -0.18) and performing more close work (mean score <16 years -0.11; 95% CI -0.18 to -0.05; mean score aged 16-25 years -0.17, 95% CI -0.24 to -0.10) than their twin. The twins who spent more time outdoors (mean score <16 years 0.09; 95% CI 0.03-0.15; mean score aged 16-25 years 0.28, 95% CI 0.15-0.41) or performed more outdoors sports (mean score <16 years 0.13; 95% CI 0.04-0.21; mean score aged 16-25 years 0.23, 95% CI 0.10-0.36) were less likely to be myopic than their twin. CONCLUSIONS: This study has confirmed known environmental risk factors for myopia. These data will allow selection of discordant twins for epigenetic analysis to advance knowledge of mechanisms of refractive error development. PMID- 26376776 TI - Early pro-inflammatory cytokine elevations in the DBA/2J mouse model of glaucoma. AB - BACKGROUND: Neuroinflammation-astrogliosis, microglial activation, and changes in cytokine signaling-is a prominent feature of neurodegenerative disorders. Glaucoma is a group of chronic neurodegenerative conditions that make up the leading cause of irreversible blindness worldwide. Neuroinflammation has been postulated to play a significant role in the pathogenesis and progression of glaucomatous neurodegeneration. Though much is known regarding inflammation in the eye in glaucoma, little is known about cytokine activity outside of the retina where pathologies develop early. METHODS: We traced the primary visual projection from the eye to the superior colliculus (SC) in DBA/2J and DBA/2J.Gpnmb (+) (control) mice using the anterograde tracer cholera toxin-B (CTB) to assay axonal transport deficits. Forty-eight hours later, visual structures were microdissected from fresh tissue based on transport outcome. Using magnetic bead multiplexing assays, we measured levels of 20 cytokines in the retina, proximal and distal optic nerves, CTB-positive and negative SC subdivisions, cerebellum, and serum at different ages representing different stages of pathology. RESULTS: Pro- and anti-inflammatory cytokine levels in mice often changed in the same direction based on strain, age, and tissue. Significant elevations in retinal pro-inflammatory cytokines were observed in young DBA/2J mice compared to controls, followed by an age-dependent decrease in the DBA/2J mice. Proximal optic nerve of young DBA/2J mice showed a 50 % or greater decrease in levels of certain cytokines compared to older DBA/2J cohorts and controls, while both proximal and distal optic nerve of DBA/2Js showed elevations in IL 1beta at all ages compared to controls. Pro-inflammatory cytokine IL-6 levels varied in accordance with transport outcome in the SC: IL-6 was elevated 44-80 % in glaucomatous DBA/2J collicular regions deficient in anterograde transport from retinal ganglion cells (RGCs) compared to areas with intact transport. CONCLUSION: Dysregulation of cytokine signaling in the RGC projection of DBA/2J mice was evident early in distal retinal targets, well before intraocular pressure elevation or axonal degeneration begins. PMID- 26376777 TI - Role of pulmonary microvascular endothelial cell apoptosis in murine sepsis induced lung injury in vivo. AB - BACKGROUND: Sepsis remains a common and serious condition with significant morbidity and mortality due to multiple organ dysfunction, especially acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Sepsis-induced ALI is characterized by injury and dysfunction of the pulmonary microvasculature and pulmonary microvascular endothelial cells (PMVEC), resulting in enhanced pulmonary microvascular sequestration and pulmonary infiltration of polymorphonuclear leukocytes (PMN) as well as disruption of the normal alveolo capillary permeability barrier with leak of albumin-rich edema fluid into pulmonary interstitium and alveoli. The role of PMVEC death and specifically apoptosis in septic pulmonary microvascular dysfunction in vivo has not been established. METHODS: In a murine cecal ligation/perforation (CLP) model of sepsis, we quantified and correlated time-dependent changes in pulmonary microvascular Evans blue (EB)-labeled albumin permeability with (1) PMVEC death (propidium iodide [PI]-staining) by both fluorescent intravital videomicroscopy (IVVM) and histology, and (2) PMVEC apoptosis using histologic fluorescent microscopic assessment of a panel of 3 markers: cell surface phosphatidylserine (detected by Annexin V binding), caspase activation (detected by FLIVO labeling), and DNA fragmentation (TUNEL labeling). RESULTS: Compared to sham mice, CLP sepsis resulted in pulmonary microvascular barrier dysfunction, quantified by increased EB-albumin leak, and PMVEC death (PI+ staining) as early as 2 h and more marked by 4 h after CLP. Septic PMVEC also exhibited increased presence of all 3 markers of apoptosis (Annexin V+, FLIVO+, TUNEL+) as early as 30 mins--1 h after CLP-sepsis, which all similarly increased markedly until 4 h. The time dependent changes in septic pulmonary microvascular albumin-permeability barrier dysfunction were highly correlated with PMVEC death (PI+; r = 0.976, p < 0.01) and PMVEC apoptosis (FLIVO+; r = 0.991, p < 0.01). Treatment with the pan-caspase inhibitor Q-VD prior to CLP reduced PMVEC death/apoptosis and attenuated septic pulmonary microvascular dysfunction, including both albumin-permeability barrier dysfunction and pulmonary microvascular PMN sequestration (p < 0.05). Septic PMVEC apoptosis and pulmonary microvascular dysfunction were also abrogated following CLP-sepsis in mice deficient in iNOS (Nos2 (-/-)) or NADPH oxidase (p47 (phox-/-) or gp91 (phox-/-)) and in wild-type mice treated with the NADPH oxidase inhibitor, apocynin. CONCLUSIONS: Septic murine pulmonary microvascular dysfunction in vivo is due to PMVEC death, which is mediated through caspase dependent apoptosis and iNOS/NADPH-oxidase dependent signaling. PMID- 26376778 TI - Nutritional parameters predicting pressure ulcers and short-term mortality in patients with minimal conscious state as a result of traumatic and non-traumatic acquired brain injury. AB - BACKGROUND: The association between malnutrition and worse outcomes as pressure ulcers and mortality is well established in a variety of setting. Currently none investigation was conducted in patients with long-term consequences of the acquired brain injury in which recovery from brain injury could be influenced by secondary complications. The aim of this study was to investigate the association between various nutritional status parameters (in particular albumin) and pressure ulcers formation and short-term mortality in minimal conscious state patients. METHODS: In this prospective, observational study of 5-months duration, a 30 patients sample admitted to a Neurological Institute was considered. All patients underwent a complete medical examination. Anthropometric parameters like mid-arm circumference and mid-arm muscle circumference and nutritional parameters as serum albumin and blood hemoglobin concentration were assessed. RESULTS: At univariate and logistic regression analysis, mid-arm circumference (p = 0.04; beta = -0.89), mid-arm muscle circumference (p = 0.050; beta = -1.29), hemoglobin (p = 0.04, beta -1.1) and albumin (p = 0.04, beta -7.91) were inversely associated with pressure ulcers. The area under the ROC curve for albumin to predict sores was 0.76 (p = 0.02) and mortality was 0.83 (p = 0.03). Patient with lower albumin had significantly higher short-term mortality than those with higher serum albumin (p = 0.03; chi(2) test = 6.47). CONCLUSION: Albumin, haemoglobin and mid-arm circumference are inversely associated with pressure ulcers. Albumin is a prognostic index in MCS patients. Since albumin and haemoglobin could be affected by a variety of factors, this association suggests to optimize nutrition and investigate on other mechanism leading to mortality and pressure ulcers. PMID- 26376779 TI - Number needed to harm in the post-marketing safety evaluation: results for rosiglitazone and pioglitazone. AB - PURPOSE: Our aim is to investigate the usefulness of metric indices in post marketing safety evaluations by estimating number needed to harm (NNH) values for cardiovascular (CV) adverse outcomes for rosiglitazone and pioglitazone. METHODS: Reports from regulatory authorities (RAs) were consulted, and Medline searches were performed to identify studies assessing CV risks [all-cause death, CV death, myocardial infarction (MI), stroke, or congestive heart failure (CHF)] for thiazolidinediones. Meta-analyses were performed to pool evidence from randomized controlled trials (RCTs) and observational studies (OS). NNHs [with 95% confidence intervals (CI)] per year were estimated for CV adverse events. RESULTS: Reports from RAs included two meta-analyses of short-term RCTs, two long term RCTs (RECORD and PROACTIVE), and a systematic review of OS (n = 29). The Medline search identified six additional OS. Statistically significant NNH values were obtained for the following: (i) rosiglitazone versus control on MI and CHF in the meta-analysis of RCTs (NNH = 16; 95%CI = 10-255; and NNH = 7; 95%CI = 5 16, respectively) and meta-analysis of OS (NNH = 12; 95%CI = 9-20; and NNH = 5; 95%CI = 32-131, respectively) and on CHF in the RECORD (NNH = 6; 95%CI = 4-14); (ii) pioglitazone versus control on CHF (NNH = 11; 95%CI = 6, 403) in the meta analysis of RCTs and PROACTIVE (NNH = 12; 95%CI = 8-43); and (iii) rosiglitazone versus pioglitazone on MI (NNH = 69; 95%CI = 32-379), stroke (NNH = 36; 95%CI = 20-225), CHF (NNH = 33; 95%CI = 19-47), and all-cause death (NNH = 63; 95%CI = 49 100) in the meta-analysis of OS. CONCLUSION: The NNH values suggested an increased CV risk with rosiglitazone versus pioglitazone across several sources of information. The inclusion of objective metrics in post-marketing drug's benefit-risk assessments could be of increased value and help RAs to make consistent decisions on drug safety. PMID- 26376780 TI - Neamine and 2-deoxystreptamine neomycin derivatives exhibit antinociceptive activity in rat models of phasic, incision and neuropathic pain. AB - OBJECTIVES: To assess the antinociceptive activity of the neomycin derivatives neamine and 2-deoxystreptamine following intraspinal administration in rats. METHODS: We used the tail-flick test and measured the threshold to mechanical stimulation in models of incisional and neuropathic pain. KEY FINDINGS: The derivatives produced antinociception in the tail-flick test and reduced mechanical allodynia in models of incisional and neuropathic pain. The approximate ED50 in milligrams (confidence limits in parenthesis) in these tests were 1.35 mg (0.61; 2.95), 0.20 mg (0.14; 0.27) and 0.28 mg (0.12; 0.63) for neamine, and 1.05 mg (0.68; 1.60), 0.78 mg (0.776; 0.783) and 0.79 mg (0.46; 1.34) for 2-deoxystreptamine, respectively. Neamine was more potent than 2 deoxystreptamine in the incisional and neuropathic pain models, but they had similar potency in the tail-flick test. Tetra-azidoneamine, a neamine derivative in which free amino groups are replaced with azido groups, did not change the incisional mechanical allodynia. The reduction of incisional allodynia by neamine and 2-deoxystreptamine was transitorily antagonized by intrathecal administration of calcium chloride. CONCLUSIONS: The intraspinal administration of neamine and 2 deoxystreptamine is antinociceptive in rats. The presence of amino groups in the structure of these derivatives is fundamental to their antinociceptive effect, which may be due to a calcium antagonist activity. PMID- 26376781 TI - Primary pulmonary melanoma: a report of two cases. AB - Malignant melanoma is a refractory malignancy with a dismal prognosis. It generally arises from the skin in most cases, and cases of primary pulmonary malignant melanoma are rare and often behave aggressively. We have treated two cases of localized primary pulmonary malignant melanoma using surgical resection. Pulmonary malignant melanomas often metastasize to the brain and liver; one of our cases exhibited metastasis to the cecum at about 8 months after surgery. Because cutaneous melanomas often carry activating mutations in the BRAF gene (V600E), we performed a BRAF mutational analysis using direct sequencing for both of these tumors arising from the lung. However, no BRAF mutations were detected. We detected a p53 mutation, which was thought to be a potential somatic mutation, in one of the two cases using a sequencing panel targeting 20 lung cancer-related genes. Although we also checked the expression of programmed death ligand 1 (PD L1) on the surface of the tumor cells by immunohistochemical testing, neither of our two cases expressed PD-L1. Further molecular analyses may uncover the characteristics of primary pulmonary malignant melanomas. PMID- 26376782 TI - Optimizing appointment template and number of staff of an OB/GYN clinic--micro and macro simulation analyses. AB - BACKGROUND: The Department of Obstetrics and Gynecology (OB/GYN) at the University of Arkansas for Medical Sciences (UAMS) tested various, new system restructuring ideas such as varying number of different types of nurses to reduce patient wait times for its outpatient clinic, often with little or no effect on waiting time. Witnessing little progress despite these time-intensive interventions, we sought an alternative way to intervene the clinic without affecting the normal clinic operations. AIM: The aim is to identify the optimal (1) time duration between appointments and (2) number of nurses to reduce wait time of patients in the clinic. METHODS: We developed a discrete-event computer simulation model for the OB/GYN clinic. By using the patient tracker (PT) data, appropriate probability distributions of service times of staff were fitted to model different variability in staff service times. These distributions were used to fine-tune the simulation model. We then validated the model by comparing the simulated wait times with the actual wait times calculated from the PT data. The validated model was then used to carry out "what-if" analyses. RESULTS: The best scenario yielded 16 min between morning appointments, 19 min between afternoon appointments, and addition of one medical assistant. Besides removing all peak wait times and bottlenecks around noon and late in the afternoon, the best scenario yielded 39.84 % (p<.001), 30.31 % (p<.001), and 15.12 % (p<.001) improvement in patients' average wait times for providers in the exam rooms, average total wait time at various locations and average total spent time in the clinic, respectively. This is achieved without any compromise in the utilization of the staff and in serving all patients by 5 pm. CONCLUSIONS: A discrete-event simulation model is developed, validated, and used to carry out "what-if" scenarios to identify the optimal time between appointments and number of nurses. Using the model, we achieved a significant improvement in wait time of patients in the clinic, which the clinic management initially had difficulty achieving through manual interventions. The model provides a tool for the clinic management to test new ideas to improve the performance of other UAMS OB/GYN clinics. PMID- 26376784 TI - Molecularly imprinted solid-phase extraction coupled with ultra high performance liquid chromatography and fluorescence detection for the determination of estrogens and their metabolites in wastewater. AB - Estrogens are an important class of endocrine-disrupting compounds, and their contamination of environmental waters through the effluents of wastewater treatment plants could have an important impact on aquatic biota, even at low concentrations. For this reason, the development of selective and sensitive extraction methodologies, which permit the identification and quantification of these compounds at trace level concentrations, is very important. In this study, a quantitative method based on molecularly imprinted solid phase extraction coupled to ultra high performance liquid chromatography with fluorescence detection has been developed. It has been used for the simultaneous determination of three estrogens and two of their metabolites in water samples from wastewater treatment plants. The method developed presents satisfactory limits of detection (between 0.18 and 0.45 ng.mL-1 ), good recoveries (higher than 60%) and low relative standard deviations (under 10%). The method was used to analyze wastewater from a veterinary hospital as well as influent and effluent samples of a wastewater treatment plant of Gran Canaria (Spain) The concentrations of the detected hormones ranged from 1.35 to 2.57 ng.mL-1 . PMID- 26376783 TI - Mitochondrial and bioenergetic dysfunction in trauma-induced painful peripheral neuropathy. AB - BACKGROUND: Mitochondrial dysfunction is observed in various neuropathic pain phenotypes, such as chemotherapy induced neuropathy, diabetic neuropathy, HIV associated neuropathy, and in Charcot-Marie-Tooth neuropathy. To investigate whether mitochondrial dysfunction is present in trauma-induced painful mononeuropathy, a time-course of mitochondrial function and bioenergetics was characterized in the mouse partial sciatic nerve ligation model. RESULTS: Traumatic nerve injury induces increased metabolic indices of the nerve, resulting in increased oxygen consumption and increased glycolysis. Increased metabolic needs of the nerve are concomitant with bioenergetic and mitochondrial dysfunction. Mitochondrial dysfunction is characterized by reduced ATP synthase activity, reduced electron transport chain activity, and increased futile proton cycling. Bioenergetic dysfunction is characterized by reduced glycolytic reserve, reduced glycolytic capacity, and increased non-glycolytic acidification. CONCLUSION: Traumatic peripheral nerve injury induces persistent mitochondrial and bioenergetic dysfunction which implies that pharmacological agents which seek to normalize mitochondrial and bioenergetic dysfunction could be expected to be beneficial for pain treatment. Increases in both glycolytic acidification and non glycolytic acidification suggest that pH sensitive drugs which preferentially act on acidic tissue will have the ability to preferential act on injured nerves without affecting healthy tissues. PMID- 26376785 TI - Cytokine Contents in Chronic Lymphocytic Leukemia: Association with ZAP70 Expression. AB - OBJECTIVE: Chronic lymphocytic leukemia (CLL) is a disease that shows varying clinical progression, and expression of the protein tyrosine kinase ZAP70 has been described as a very valuable prognostic factor. Patients with ZAP70 positivity are characterized by worse clinical course and significantly shorter progression-free and overall survival. In this study, intracytoplasmic interferon gamma (IFN-gamma) and interleukin-4 (IL-4) content of T, B, and CLL cells in CLL patients and their correlations with Rai staging and ZAP70 positivity were investigated. MATERIALS AND METHODS: CLL patients newly diagnosed or in follow-up at the Istanbul University Istanbul Medical Faculty Hematology Department were included in this study. These patients were classified according to Rai staging and ZAP70 expression. IL-4, IFN-gamma, and ZAP70 expressions in peripheral blood T, B, and CLL cells were measured by four-color flow cytometry. RESULTS: There was a statistically significant correlation between advanced disease and ZAP70 positivity. IL-4-secreting T cells were significantly increased; however, IFN gamma secretion was significantly decreased in CLL patients compared to healthy individuals, whereas IL-4-secreting B cells were significantly diminished in contrast to T cells. CONCLUSION: These findings suggest damage in the cellular immunity and that IL-4 might lead to many complications and may be important in disease progression. PMID- 26376787 TI - Cytotoxic effects of chemotherapy on cancer and immune cells: how can it be modulated to generate novel therapeutic strategies? AB - The first objective to use chemotherapy is to kill cancer cells. However, it is common knowledge that these drugs can also damage healthy host cells, especially immune cells, and thus impair the endogenous antitumor response. Here, we focus on the cytotoxic effects of chemotherapy on tumor cells and immune cells. It is not enough to simply kill cancer cells, and causing immunogenic cell death will impair the adaptive immune system's ability to fight the remaining cancer cells. On the other hand, the killing of immune cells can also enhance tumor growth. A study of the repercussions of the cytotoxic effects of chemotherapy is of great importance to evaluate the antitumor response. Strategies can be proposed to promote the 'good way' for cancer cells to die and to avoid the adverse side effects of chemotherapy on immune cells in order to strengthen the role of the immune system in the antitumor response. PMID- 26376786 TI - Differential expression of the Nrf2-linked genes in pediatric septic shock. AB - INTRODUCTION: Experimental data from animal models of sepsis support a role for a transcription factor, nuclear erythroid-related factor 2 p45-related factor 2 (Nrf2), as a master regulator of antioxidant and detoxifying genes and intermediary metabolism during stress. Prior analysis of a pediatric septic shock transcriptomic database showed that the Nrf2 response is a top 5 upregulated signaling pathway in early pediatric septic shock. METHODS: We conducted a focused analysis of 267 Nrf2-linked genes using a multicenter, genome-wide expression database of 180 children with septic shock 10 years of age or younger and 53 healthy controls. The analysis involved RNA isolated from whole blood within 24 h of pediatric intensive care unit admission for septic shock and a false discovery rate of 5 %. We compared differentially expressed genes from (1) patients with septic shock and healthy controls and (2) across validated gene expression-based subclasses of pediatric septic shock (endotypes A and B) using several bioinformatic methods. RESULTS: We found upregulation of 123 Nrf2-linked genes in children with septic shock. The top gene network represented by these genes contained primarily enzymes with oxidoreductase activity involved in cellular lipid metabolism that were highly connected to the peroxisome proliferator activated receptor and the retinoic acid receptor families. Endotype A, which had higher organ failure burden and mortality, exhibited a greater downregulation of Nrf2-linked genes than endotype B, with 92 genes differentially regulated between endotypes. CONCLUSIONS: Our findings indicate that Nrf2-linked genes may contribute to alterations in oxidative signaling and intermediary metabolism in pediatric septic shock. PMID- 26376788 TI - Highly sensitive colorimetric detection of glucose in a serum based on DNA embeded Au@Ag core-shell nanoparticles. AB - Glucose is a key energy substance in diverse biology and closely related to the life activities of the organism. To develop a simple and sensitive method for glucose detection is extremely urgent but still remains a key challenge. Herein, we report a colorimetric glucose sensor in a homogeneous system based on DNA embedded core-shell Au@Ag nanoparticles. In this assay, a glucose substrate was first catalytically oxidized by glucose oxidase to produce H2O2 which would further oxidize and gradually etch the outer silver shell of Au@Ag nanoparticles. Afterwards, the solution color changed from yellow to red and the surface plasmon resonance (SPR) band of Au@Ag nanoparticles declined and red-shifted from 430 to 516 nm. Compared with previous silver-based glucose colorimetric detection strategies, the distinctive SPR band change is superior to the color variation, which is critical to the high sensitivity of this assay. Benefiting from the outstanding optical property, robust stability and well-dispersion of the core shell Au@AgNPs hybrid, this colorimetric assay obtained a detection limit of glucose as low as 10 nM, which is at least a 10-fold improvement over other AgNPs based procedures. Moreover, this optical biosensor was successfully employed to the determination of glucose in fetal bovine serum. PMID- 26376789 TI - Association of interferon-gamma inducible protein 10 polymorphism with treatment response to pegylated interferon in HBeAg-positive chronic hepatitis B. AB - BACKGROUND: Interferon-gamma inducible protein 10 (IP-10) plays an important role in the clinical outcome of chronic hepatitis B (CHB). This study aimed to investigate the association between single nucleotide polymorphisms (SNPs) G-201A of the IP-10 gene and treatment response to pegylated interferon (PEG-IFN) in patients with hepatitis B e antigen (HBeAg)-positive CHB. METHODS: We retrospectively analysed data of patients with HBeAg-positive CHB treated with PEG-IFN for 48 weeks. Virological response (VR) was defined as HBeAg clearance and HBV DNA <2,000 IU/ml at 24 weeks post-treatment. The SNPs G-201A, IFNL3 (rs12979860) and HLA-DPA1 (rs3077) were assessed. RESULTS: Among 107 patients, VR was achieved in 45 (42.1%) patients. Hepatitis B surface antigen (HBsAg) clearance and decline (<100 IU/ml) were observed in 10 (9.3%) and 22 (20.6%) patients, respectively. The distribution of GG, GA and AA genotypes of G-201A was 76.6%, 19.6% and 3.7%, respectively. Patients with GG genotype, compared to those with non-GG genotype, achieved higher VR rate (48.8% versus 19.2%; P=0.011), decreased HBsAg (25.6% versus 4.0%; P=0.019), and demonstrated a trend in HBsAg clearance (11.0% versus 4%; P=0.294). Patients with GG genotype had more rapid HBsAg decline and higher baseline serum IP-10 levels than those with non-GG genotype (432.2 +/-339.0 versus 257.3 +/-145.7 pg/ml; P=0.028). SNPs rs12979860 and rs3077 were not associated with VR. Logistic regression analysis suggested that SNP G-201A was an independent predictor of VR (odds ratio 3.81, 95% CI 1.31, 11.12; P=0.014). CONCLUSIONS: Data from this study demonstrated for the first time that IP-10 polymorphism is independently associated with treatment response to PEG-IFN in patients with HBeAg-positive CHB. PMID- 26376790 TI - Neurocytoma arising from a mature ovary teratoma: a case report. AB - Central neurocytoma/extraventricular neurocytoma is a central nervous system (CNS) tumor composed of uniform round cells with neuronal differentiation. The typical lesions of central neurocytoma/extraventricular neurocytoma are at the interventricular foramen of the lateral ventricles (central neurocytoma) or brain parenchyma (extraventricular neurocytoma). Mature teratoma is a benign germ cell tumor commonly found in young women. Herein, we report a 24-year-old female with neurocytoma in a mature teratoma of the right ovary. The histological examinations showed mature epidermis, skin appendages, adipose and bone tissues in the tumor; microscopic foci of immature cartilage tissues were also found in some parts. In addition, massive solid sheets and uniform round tumor cells were found in the neuroectodermal tissues, with the formation of neuropil-like islands. Immunohistochemical examinations showed that the tumor cells were synaptophysin- and NeuN-positive but GFAP-negative. Based on these findings, the woman was diagnosed with neurocytoma arising from mature ovary teratoma, with microscopic foci of immature cartilage tissues. This is the fourth case report of neurocytoma outside the CNS to date. PMID- 26376791 TI - Activation of peroxisome proliferator-activated receptor gamma is crucial for antitumoral effects of 6-iodolactone. AB - BACKGROUND: Molecular iodine (I2) exhibits antiproliferative and apoptotic effects on in vivo and in vitro cancer models. These effects are thought to be mediated by an iodinated arachidonic acid derivative, 6-iodolactone (6IL), and one of the proposed mechanisms is that 6IL activates Peroxisome Proliferator Activated Receptors type gamma (PPARG). These receptors have been implicated in the inhibition of carcinogenic processes, in addition to their classical role in maintaining lipid and glucose homeostasis. The aim of this study was to determine whether PPARG participates in the 6IL antiproliferative and apoptotic effects on the mammary cancer cell line MCF-7. METHODS: The 6IL/PPARG complex was inhibited by the PPARG antagonist GW9662, in both an endogenous and overexpressed (adenoviral vector infection) context, and stable PPARG-knockdown MCF-7 cells (RNA interference, confirmed with hydrolysis probes and Western blot), were used to corroborate the PPARG participation. 6IL effects on proliferation (measured by Trypan Blue exclusion) and apoptosis (phosphatidylserine identification by flow cytometer) were evaluated in conditions of chemical inhibition (GW9662) and silencing (RNA interference). A wound-healing assay was conducted on wild-type and stable PPARG-knockdown MCF-7 cells to evaluate the antimigrational effect of 6IL. Caspase-8 activity was evaluated to determine if the extrinsic pathway is involved in the effects of 6IL and I2 treatment. RESULTS: Antiproliferative and pro-apoptotic 6IL effects require the activation of PPARG. In addition, wound healing assays show that 6IL is able to inhibit MCF-7 cell migration and that PPARG plays a role in this phenomenon. Finally, the data exclude the participation of the extrinsic apoptotic pathway in 6IL- and I2-induced apoptosis. CONCLUSIONS: These results support the previously proposed mechanism, in which the I2 effects are mediated by 6IL, and they provide further support for the use of I2 as coadjuvant in breast cancer treatment. PMID- 26376792 TI - A Streptomyces coelicolor host for the heterologous expression of Type III polyketide synthase genes. AB - BACKGROUND: Recent advances in genome sequencing, combined with bioinformatic analysis, has led to the identification of numerous novel natural product gene clusters, particularly in actinomycetes of terrestrial and marine origin. Many of these gene clusters encode uncharacterised Type III polyketide synthases. To facilitate the study of these genes and their potentially novel products, we set out to construct an actinomycete expression host specifically designed for the heterologous expression of Type III PKS genes and their gene clusters. RESULTS: A derivative of Streptomyces coelicolor A3(2) designed for the expression of Type III polyketide synthase (PKS) genes was constructed from the previously engineered expression strain S. coelicolor M1152 [Deltaact Deltared Deltacpk Deltacda rpoB(C1298T)] by removal of all three of the endogenous Type III PKS genes (gcs, srsA, rppA) by PCR targeting. The resulting septuple deletion mutant, M1317, proved to be an effective surrogate host for the expression of actinobacterial Type III PKS genes: expression of the reintroduced gcs gene from S. coelicolor and of the heterologous rppA gene from Streptomyces venezuelae under the control of the constitutive ermE* promoter resulted in copious production of germicidin and flaviolin, respectively. CONCLUSIONS: The newly constructed expression host S. coelicolor M1317 should be particularly useful for the discovery and analysis of new Type III polyketide metabolites. PMID- 26376794 TI - A rare case of cerebral hydatidosis caused by a G1 genotype of Echinococcus granulosus in a cow from Iran. AB - Hydatidosis is a medically and veterinary important parasitic disease that is endemic in many parts of the world. Unilocular hydatid cysts may develop in almost any part of the body. Up to 70% of hydatid cysts are located in the liver, followed by 25% in the lungs. Cerebral hydatidosis is an uncommon manifestation of the disease, occurring in less than 1/1000 infected hosts, yet diagnosis does pose a problem. We have reported an exceptionally rare case of cerebral hydatidosis in cattle. This is the first report to describe the characteristic pathological features of the cerebral hydatidosis in cattle caused by the G1 genotype of Echinococcus granulosus. Genotypic analysis was performed on a hydatid cyst from a cow originating from southern Iran, based on the sequence analysis of the cox1 mitochondrial gene. PMID- 26376793 TI - Morphometric analyses of petioles of seedlings grown in a spaceflight experiment. AB - Gravity is a constant unidirectional stimulus on Earth, and gravitropism in plants involves three phases: perception, transduction, and response. In shoots, perception takes place within the endodermis. To investigate the cellular machinery of perception in microgravity, we conducted a spaceflight study with Arabidopsis thaliana seedlings, which were grown in microgravity in darkness using the Biological Research in Canisters (BRIC) hardware during space shuttle mission STS-131. In the 14-day-old etiolated plants, we studied seedling development and the morphological parameters of the endodermal cells in the petiole. Seedlings from the spaceflight experiment (FL) were compared to a ground control (GC), which both were in the BRIC flight hardware. In addition, to assay any potential effects from growth in spaceflight hardware, we performed another control by growing seedlings in Petri dishes in standard laboratory conditions (termed the hardware control, HC). Seed germination was significantly lower in samples grown in flight hardware (FL, GC) compared to the HC. In terms of cellular parameters of endodermal cells, the greatest differences also were between seedlings grown in spaceflight hardware (FL, GC) compared to those grown outside of this hardware (HC). Specifically, the endodermal cells were significantly smaller in seedlings grown in the BRIC system compared to those in the HC. However, a change in the shape of the cell, suggesting alterations in the cell wall, was one parameter that appears to be a true microgravity effect. Taken together, our results suggest that caution must be taken when interpreting results from the increasingly utilized BRIC spaceflight hardware system and that it is important to perform additional ground controls to aid in the analysis of spaceflight experiments. PMID- 26376795 TI - Spatial and temporal coordination of insulin granule exocytosis in intact human pancreatic islets. AB - AIMS/HYPOTHESIS: Insulin secretion is widely studied because it plays a central role in glucose homeostasis and diabetes. Processes from insulin granule fusion in beta cells to in vivo insulin secretion have been elucidated, but data at the cellular level do not fully account for several aspects of the macroscopic secretory pattern. Here we investigated how individual secretory events are coordinated spatially and temporally within intact human islets. METHODS: We used the fluorescent probe neuropeptide Y (NPY)-pHluorin to visualise insulin granule secretion in isolated intact human islets. RESULTS: We found that individual beta cells respond to increases in glucose concentration by releasing insulin granules in very discrete bursts with periods consistent with in vivo pulsatile insulin secretion. In successive secretory bursts during prolonged exposure to high glucose levels, secretory events progressively localised to preferential release sites, coinciding with the transition to second phase insulin secretion. Granule secretion was very synchronised in neighbouring beta cells, forming discrete regional clusters of activity. CONCLUSIONS/INTERPRETATION: These results reveal how individual secretory events are coordinated to produce pulsatile insulin secretion from human islets. PMID- 26376796 TI - Weight cycling and the risk of type 2 diabetes in the EPIC-Germany cohort. AB - AIMS/HYPOTHESIS: Studies on weight cycling and the risk of type 2 diabetes have revealed inconsistent results, possibly due to differences in the definition of weight fluctuations. Here, we investigated whether weight cycling during adulthood is related to diabetes risk in a large cohort study, using a complementary approach to define patterns of weight development. METHODS: Weight cycling, weight loss and weight gain were defined (1) a priori, using distinct categories, and (2) by functional principal component analysis (FPCA) to capture weight patterns in greater detail. Associations of weight cycling, weight loss and weight gain with the risk of type 2 diabetes were evaluated by Cox regression models. RESULTS: A priori defined weight cycling was associated with increased diabetes risk, compared with stable weight (HR 1.36 [95% CI 1.09, 1.68]). No significant association between FPCA-derived weight cycling and risk of diabetes was observed after adjustment for concurrent weight patterns (HR 1.19 [95% CI 0.89, 1.60]). Subgroup analyses showed that FPCA-derived weight cycling during net weight gain was associated with a higher risk of diabetes (HR 1.68 [95% CI 1.14, 2.48]). A priori defined weight gain (HR 2.08 [95% CI 1.60, 2.70]) was more clearly related to the risk of diabetes than FPCA-derived weight gain (HR 1.20 [95% CI 0.95, 1.51]), while no significant associations were observed for weight loss. CONCLUSIONS/INTERPRETATION: Overall, weight cycling may not be an independent risk factor for type 2 diabetes when accounting for concurrent patterns of weight development. However, weight cycling may pose a stronger risk of diabetes than non-cycling during net weight gain. PMID- 26376798 TI - Erratum to: The new biology of diabetes. PMID- 26376797 TI - Rapid development of cardiac dysfunction in a canine model of insulin resistance and moderate obesity. AB - AIMS/HYPOTHESIS: The worldwide incidence of obesity and diabetes continues to rise at an alarming rate. A major cause of the morbidity and mortality associated with obesity and diabetes is heart disease, yet the mechanisms that lead to cardiovascular complications remain unclear. METHODS: We performed cardiac MRI to assess left ventricular morphology and function during the development of moderate obesity and insulin resistance in a well-established canine model (n = 26). To assess the influence of dietary fat composition, we randomised animals to a traditional lard diet (rich in saturated and monounsaturated fat; n = 12), a salmon oil diet (rich in polyunsaturated fat; n = 8) or a control diet (n = 6). RESULTS: High-fat feeding with lard increased body weight and fasting insulin and markedly reduced insulin sensitivity. Lard feeding also significantly reduced left ventricular function, evidenced by a worsening of circumferential strain and impairment in left ventricular torsion. High-fat feeding with salmon oil increased body weight; however, salmon oil feeding did not impair insulin sensitivity or cardiac function. CONCLUSIONS/INTERPRETATION: These data emphasise the importance of dietary fat composition on both metabolic and cardiac function, and have important implications for the relationship between diet and health. PMID- 26376799 TI - DFT studies on the palladium-catalyzed dearomatization reaction between naphthalene allyl chloride and allyltributylstannane. AB - The Pd-catalyzed dearomatization of naphthalene allyl chloride with allyltributylstannane has been investigated using density functional theory (DFT) calculations at the B3LYP level. The calculations indicate that the (n(1) allyl)(n(3)-allyl)Pd(PH3) complex is responsible for the formation of ortho dearomatized product. Moreover it is easy to produce the ortho-dearomatized product when reductive elimination starts from (n(3)-allylnaphthalene)(n(1) allyl)Pd complex 7, while it is easy to form the para-dearomatized product when reductive elimination starts from (n(3)-allylnaphthalene)(n(1)-allyl)Pd complex 9. The Stille coupling products can't be produced due to high reaction energy barrier. Graphical Abstract Two mechanisms of dearomatization are investigated by DFT, and (n(1)-allyl)(n(3)-allyl)Pd(PH3) complexes are the main intermediates for ortho-dearomatized product. PMID- 26376800 TI - Diagnosis, Treatment and Long-Term Follow Up of Patients with ADA Deficiency: a Single-Center Experience. AB - PURPOSE: We carried out a retrospective analysis of 27 patients with Adenosine Deaminase (ADA) deficiency diagnosed in a single center from 1997 to the 2013, for evaluating whether data regarding types of disease-inducing mutations, biochemical and immunological features as well as clinical outcomes of patients treated with enzyme replacement or transplantation, were comparable to those obtained in multicenter studies. METHODS: The ADA deficiency diagnosis was performed with biochemical, immunological and molecular techniques. Ten patients treated with hematopoietic stem cell transplantation and three in treatment with enzyme replacement were followed up in our center. RESULTS: Twenty-four different mutations were identified and five were not previously reported. Identical mutations were found among patients from the same Romani ethnic group or from the same geographical region. A more rapid recovery was observed in enzyme replacement treated patients in comparison with those transplanted that, however, showed a continuous and long-lasting improvement both in terms of immune and metabolic recovery. CONCLUSION: The data obtained in our single center are comparable with those that have been reported in multicenter surveys. PMID- 26376801 TI - FOXO3a and Posttranslational Modifications Mediate Glucocorticoid Sensitivity in B-ALL. AB - Glucocorticoids are widely used to treat B acute lymphoblastic leukemia (B-ALL); however, the molecular mechanism underlying glucocorticoid response and resistance is unclear. In this study, the role and regulation of FOXO3a in mediating the dexamethasone response in B-ALL were investigated. The results show that FOXO3a mediates the cytotoxic function of dexamethasone. In response to dexamethasone, it was found that FOXO3a translocates into the nucleus, where it induces the expression of downstream targets, including p27Kip1 and Bim, important for proliferative arrest and cell death in the sensitive RS4;11 and SUP B15 B-ALL cells. FOXO3a activation by dexamethasone is mediated partially through the suppression of the PI3K/Akt signaling cascade. Furthermore, two posttranslational modifications were uncovered, phosphorylation on Ser-7 and acetylation on Lys-242/5, that associated with FOXO3a activation by dexamethasone. Immunoblot analysis showed that the phosphorylation on Ser-7 of FOXO3a is associated with p38/JNK activation, whereas the acetylation on Lys 242/5 is correlated with the downregulation of SIRT1/2/6 and the induction of the acetyltransferase CBP/p300. Collectively, these results indicate that FOXO3a is essential for dexamethasone response in B-ALL cells, and its nuclear translocation and activation is associated with its phosphorylation on Ser-7 and acetylation on Lys-242/245. These posttranslational events can be exploited as biomarkers for B-ALL diagnosis and as drug targets for B-ALL treatment, particularly for overcoming the glucocorticoid resistance. IMPLICATIONS: FOXO3a and its posttranslational regulation are essential for dexamethasone response, and targeting FOXO3a and sirtuins may enhance the dexamethasone-induced cytotoxicity in B-ALL cells. PMID- 26376802 TI - Predictive value of PWI for blood supply and T1-spin echo MRI for consistency of pituitary adenoma. AB - INTRODUCTION: It is a common view that consistency and blood supply of pituitary adenoma (PA) can influence the surgical effect. The aim of this study was to determine whether MRI signal intensity (SI) was correlated to the consistency or blood supply of pituitary macroadenoma. METHODS: Forty eight pituitary macroadenoma patients were underwent preoperative MRI, including precontrast and contrast-enhanced (CE) T1-spin echo (T1-SE) imaging, CE-sampling perfection with application-optimized contrasts by using different flip angle evolutions (SPACE) imaging, and perfusion-weighted imaging (PWI). The tumor consistency and blood supply were determined by neurosurgeons. The expression of collagen IV and MIB-1 was detected with immunohistology. The correlation of the relative SI (rSI) values (tumor to normal frontal white matter SI) and PWI data to the tumor consistency, blood supply, and the expression level of collagen IV and MIB-1 was statistically studied by Kruskal-Wallis rank test (K-W test). RESULTS: A significant correlation was observed between the tumor consistency and the rSI on precontrast T1-SE imaging (P = 0.004) but not on CE T1-SE and CE SPACE imaging. The expression of collagen IV was also significantly associated with rSI on T1-SE imaging (P = 0.010). The blood supply was correlated with the relative CBV (rCBV) (P = 0.030). In addition, the expression of MIB-1 was correlated with rSI of CE T1-SE imaging (P = 0.007). CONCLUSION: Our results suggest that T1-SE imaging may be a simple and useful method for predicting consistency of PA. CBV value can provide helpful information for assessing the blood supply of pituitary macroadenoma. PMID- 26376803 TI - Association between baseline peri-infarct magnetic resonance spectroscopy and regional white matter atrophy after stroke. AB - INTRODUCTION: Cerebral atrophy after stroke is associated with poor functional outcome. The prediction and prevention of post-stroke brain atrophy could therefore represent a target for neurorestorative therapies. We investigated the associations between peri-infarct metabolite concentrations measured by quantitative MRS and brain volume change in the infarct hemisphere after stroke. METHODS: Twenty patients with ischemic stroke were enrolled. Patients underwent 3T-MRI within 1 week of onset, and at 1 and 3 months. At the baseline scan, an MRS voxel was placed manually in the peri-infarct area and another in the corresponding contralateral region. Volumetric analysis of T1 images was performed using two automated processing packages. Changes in gray and white matter volume were assessed as percentage change between 1 and 3 months. RESULTS: Mean concentrations (institutional units) of N-acetylaspartic acid (NAA) (6.1 vs 7.0, p = 0.039), total creatine (Cr+PCr) (5.4 vs 5.8, p = 0.043), and inositol (4.5 vs 5.0, p = 0.014), were significantly lower in the peri-infarct region compared with the contralateral hemisphere. There was a significant correlation between baseline peri-infarct NAA and white matter volume change in the infarct hemisphere between 1 and 3 months, with lower NAA being associated with subsequent white matter atrophy (Spearman's rho = 0.66, p = 0.010). The baseline concentration of Cr+PCr was also significantly correlated with white matter atrophy in the infarct hemisphere (Spearman's rho = 0.59, p = 0.027). Both of these associations were significant after adjustment for the false discovery rate and were validated using the secondary volumetric method. CONCLUSION: MRS may be useful in the prediction of white matter atrophy post-stroke and in the testing of novel neurorestorative therapies. PMID- 26376804 TI - Radiological findings in cerebral venous thrombosis presenting as subarachnoid hemorrhage: a series of 22 cases. AB - INTRODUCTION: The main objectives of the present study are to assess the incidence of cerebral venous thrombosis (CVT) presenting as isolated subarachnoid hemorrhage (SAH) and to determine the occurrence of cortical venous thrombosis (CoVT). METHODS: Among 332 patients with CVT, investigated with the same CT and MR standardized protocol, 33 (10 %) presented with SAH, associated in 11 cases with hemorrhagic infarct or intracerebral hemorrhage. This study is based on 22 cases of CVT presenting as SAH in the absence of hemorrhagic brain lesion. Diagnosis of sinus thrombosis was established on T2* and magnetic resonance venography and that of CoVT on T2* sequence. Diagnostic of SAH was based on fluid attenuated inversion recovery (FLAIR) sequence. RESULTS: CVT involved lateral sinus in 18 patients, superior sagittal sinus in 16, and straight sinus in 1. Cortical veins were involved in all patients, in continuity with dural sinus thrombosis when present. SAH was circumscribed to few sulci in all cases and mainly localized at the convexity (21 cases). CoVT implied different areas on the same side in four patients and was bilateral in seven. There was no perimesencephalic or basal cisterns hemorrhage. Cortical swelling was present in 12 cases, associated with localized edema. All patients except one had a favorable outcome. CONCLUSION: This report shows that the incidence of CVT presenting as isolated SAH is evaluated to 6.4 % and that SAH is, in all cases, in the vicinity of CoVT and when dural thrombosis is present in continuity with it. PMID- 26376805 TI - Restoring Study 329: efficacy and harms of paroxetine and imipramine in treatment of major depression in adolescence. AB - OBJECTIVES: To reanalyse SmithKline Beecham's Study 329 (published by Keller and colleagues in 2001), the primary objective of which was to compare the efficacy and safety of paroxetine and imipramine with placebo in the treatment of adolescents with unipolar major depression. The reanalysis under the restoring invisible and abandoned trials (RIAT) initiative was done to see whether access to and reanalysis of a full dataset from a randomised controlled trial would have clinically relevant implications for evidence based medicine. DESIGN: Double blind randomised placebo controlled trial. SETTING: 12 North American academic psychiatry centres, from 20 April 1994 to 15 February 1998. PARTICIPANTS: 275 adolescents with major depression of at least eight weeks in duration. Exclusion criteria included a range of comorbid psychiatric and medical disorders and suicidality. INTERVENTIONS: Participants were randomised to eight weeks double blind treatment with paroxetine (20-40 mg), imipramine (200-300 mg), or placebo. MAIN OUTCOME MEASURES: The prespecified primary efficacy variables were change from baseline to the end of the eight week acute treatment phase in total Hamilton depression scale (HAM-D) score and the proportion of responders (HAM-D score <=8 or >=50% reduction in baseline HAM-D) at acute endpoint. Prespecified secondary outcomes were changes from baseline to endpoint in depression items in K-SADS-L, clinical global impression, autonomous functioning checklist, self perception profile, and sickness impact scale; predictors of response; and number of patients who relapse during the maintenance phase. Adverse experiences were to be compared primarily by using descriptive statistics. No coding dictionary was prespecified. RESULTS: The efficacy of paroxetine and imipramine was not statistically or clinically significantly different from placebo for any prespecified primary or secondary efficacy outcome. HAM-D scores decreased by 10.7 (least squares mean) (95% confidence interval 9.1 to 12.3), 9.0 (7.4 to 10.5), and 9.1 (7.5 to 10.7) points, respectively, for the paroxetine, imipramine and placebo groups (P=0.20). There were clinically significant increases in harms, including suicidal ideation and behaviour and other serious adverse events in the paroxetine group and cardiovascular problems in the imipramine group. CONCLUSIONS: Neither paroxetine nor high dose imipramine showed efficacy for major depression in adolescents, and there was an increase in harms with both drugs. Access to primary data from trials has important implications for both clinical practice and research, including that published conclusions about efficacy and safety should not be read as authoritative. The reanalysis of Study 329 illustrates the necessity of making primary trial data and protocols available to increase the rigour of the evidence base. PMID- 26376807 TI - [Annual report of the working group on informatics of the German Society of Pathology]. PMID- 26376808 TI - [Minutes of the meeting of the working group on bone, joint and soft tissue pathology: Congress of the German Society of Pathology on 31 May 2015]. PMID- 26376806 TI - New Insights into Epigenetic and Pharmacological Regulation of Amyloid-Degrading Enzymes. AB - Currently, deficit of amyloid beta-peptide (Abeta) clearance from the brain is considered as one of the possible causes of amyloid accumulation and neuronal death in the sporadic form of Alzheimer's disease (AD). Abeta clearance can involve either specific proteases present in the brain or Abeta-binding/transport proteins. Among amyloid-degrading enzymes the most intensively studied are neprilysin (NEP) and insulin-degrading enzyme (IDE). Since ageing and development of brain pathologies is often accompanied by a deficit in the levels of expression and activity of these enzymes in the brain, there is an urgent need to understand the mechanisms involved in their regulation. We have recently reported that NEP and also an Abeta-transport protein, transthyretin are epigenetically co regulated by the APP intracellular domain (AICD) and this regulation depends on the cell type and APP695 isoform expression in a process that can be regulated by the tyrosine kinase inhibitor, Gleevec. We have now extended our work and shown that, unlike NEP, another amyloid-degrading enzyme, IDE, is not related to over expression of APP695 in neuroblastoma SH-SY5Y cells but is up-regulated by APP751 and APP770 isoforms independently of AICD but correlating with reduced HDAC1 binding to its promoter. Studying the effect of the nuclear retinoid X receptor agonist, bexarotene, on NEP and IDE expression, we have found that both enzymes can be up-regulated by this compound but this mechanism is not APP-isoform specific and does not involve AICD but, on the contrary, affects HDAC1 occupancy on the NEP gene promoter. These new insights into the mechanisms of NEP and IDE regulation suggest possible pharmacological targets in developing AD therapies. PMID- 26376809 TI - Opening new doors for understanding eukaryotic RNA splicing. PMID- 26376810 TI - Exploring CTCF and cohesin related chromatin architecture at HOXA gene cluster in primary human fibroblasts. AB - Spatial expression patterns of homeobox (HOX) genes delineate positional identity of primary fibroblasts from different topographic sites. The molecular mechanism underlying the establishing or maintaining of HOX gene expression pattern remains an attractive developmental issue to be addressed. Our previous work suggested a critical role of CTCF/cohesin-mediated higher- order chromatin structure in RA induced HOXA activation in human teratocarcinoma NT2/D1 cells. This study investigated the recruitment of CTCF and cohesin, and the higher-order chromatin structure of the HOXA locus in fetal lung and adult foreskin fibroblasts, which display complementary HOXA gene expression patterns. Chromatin contacts between the CTCF-binding sites were observed with lower frequency in human foreskin fibroblasts. This observation is consistent with the lower level of cohesin recruitment and 5' HOXA gene expression in the same cells. We also showed that CTCF-binding site A56 (CBSA56) related chromatin structures exhibit the most notable changes in between the two types of cell, and hence may stand for one of the key CTCF-binding sites for cell-type specific chromatin structure organization. Together, these results imply that CTCF/cohesin coordinates HOXA cluster higher-order chromatin structure and expression during development, and provide insight into the relationship between cell-type specific chromatin organization and the spatial collinearity. PMID- 26376811 TI - A Golden Opportunity: Prevention in the Workplace. PMID- 26376812 TI - Association Study of CHRNA7 Promoter Variants with Sensory and Sensorimotor Gating in Schizophrenia Patients and Healthy Controls: A Danish Case-Control Study. AB - Schizophrenia is a severe psychiatric disorder with a core component of impaired cognitive function still remaining as one of the greatest challenges in the pharmacological treatment of the disorder. The CHRNA7 gene, encoding the subunit of the human alpha7 nicotinic acetylcholine receptor (alpha7nAChR), is suggested as a susceptibility factor for schizophrenia. CHRNA7 has also been genetically linked to the P50 auditory evoked potential deficit, a candidate endophenotype of schizophrenia, but not to prepulse inhibition of the startle reflex (PPI). In this study, 95 antipsychotic-naive schizophrenic patients and 450 unaffected controls were screened for CHRNA7 promoter variants to investigate the association with schizophrenia, P50 suppression and PPI. We found that the promoter variant -194C (rs28531779) was significantly associated with schizophrenia, but did not find any association of this variant with P50 suppression or PPI. In addition, individuals with CHRNA7 promoter variants had elevated startle magnitude in pulse-alone trials compared to individuals without a variant. The present findings provide further support for a role of the alpha7nAChR in schizophrenia and show a genetic link between CHRNA7 and startle magnitude, indicating that cholinergic neurotransmission involving the alpha7nAChR could be involved in sensory registration processes. PMID- 26376813 TI - RE: Bartula I, Sherman KA: Development and validation of the Female Sexual Function Index adaptation for breast cancer patients (FSFI-BC). PMID- 26376814 TI - The -137G/C Polymorphism in Interleukin-18 Gene Promoter Contributes to Chronic Lymphocytic and Chronic Myelogenous Leukemia Risk in Turkish Patients. AB - OBJECTIVE: Interleukin-18 (IL-18) is a cytokine that belongs to the IL-1 superfamily and is secreted by various immune and nonimmune cells. Evidence has shown that IL-18 has both anticancer and procancer effects. The aim of this study was to evaluate the relationship between IL-18 gene polymorphisms and susceptibility to chronic lymphocytic leukemias (CLL) and chronic myelogenous leukemias (CML) in Turkish patients. MATERIALS AND METHODS: The frequencies of polymorphisms (rs61667799(G/T), rs5744227(C/G), rs5744228(A/G), and rs187238(G/C)) were studied in 20 CLL patients, 30 CML patients, and 30 healthy individuals. The genotyping was performed by polymerase chain reaction and DNA sequencing analysis. RESULTS: Significant associations were detected between the IL-18 rs187238(G/C) polymorphism and chronic leukemia. A higher prevalence of the C allele was found in CML cases with respect to controls. The GC heterozygous and CC homozygous genotypes were associated with risk of CML when compared with controls. However, prevalence of the C allele was not significantly high in CLL cases with respect to controls. There was only a significant difference between the homozygous CC genotype of CLL patients and the control group; thus, it can be concluded that the CC genotype may be associated with the risk of CLL. Based on our data, there were no significant associations between the IL-18 rs61667799(G/T), rs5744227(C/G), or rs5744228(A/G) polymorphisms and CLL or CML. CONCLUSIONS: IL-18 gene promoter rs187238(G/C) polymorphism is associated with chronic leukemia in the Turkish population. However, due to the limited number of studied patients, these are preliminary results that show the association between -137G/C polymorphism and patients (CLL and CML). Further large-scale studies combined with haplotype and expression analysis are required to validate the current findings. PMID- 26376815 TI - Genetic and morphological evidence for introgression between three species of willows. AB - BACKGROUND: Hybridization and introgression are said to occur relatively frequently in plants, and in particular among different species of willows. However, data on the actual frequency of natural hybridization and introgression is rare. Here, we report the first fine-scale genetic analysis of a contact zone shared between the three basket willow species, Salix dasyclados, S. schwerinii and S. viminalis in the vicinity of the Lake Baikal in Southern Siberia. Individuals were sampled in fourteen populations and classified as pure species or hybrids based on a set of morphological characters. They were then genotyped at 384 nuclear SNP and four chloroplast SSR loci. The STRUCTURE and NewHybrids softwares were used to estimate the frequency and direction of hybridization using genotypic data at the nuclear SNP loci. RESULTS: As many as 19 % of the genotyped individuals were classified as introgressed individuals and these were mainly encountered in the centre of the contact zone. All introgressed individuals were backcrosses to S. viminalis or S. schwerinii and no F1 or F2 hybrids were found. The rest of the genotyped individuals were classified as pure species and formed two clusters, one with S. schwerinii individuals and the other with S. viminalis and S. dasyclados individuals. The two clusters were significantly genetically differentiated, with F ST = 0.333 (0.282-0.382, p < 0.001). In contrast, for the chloroplast haplotypes, no genetic differentiation was observed as they were completely shared between the species. Based on morphological classification only 5 % of the individuals were classified as introgressed individuals, which was much less than what was detected using genotypic data. CONCLUSIONS: We have discovered a new willow hybrid zone with relatively high frequency of introgressed individuals. The low frequency of F1 hybrids indicates that ongoing hybridization is limited, which could be because of the presence of reproductive barriers or simply because the conditions are not favorable for hybridization. We further conclude that in order to get a complete picture of the species composition of a hybrid zone it is necessary to use a combination of morphological characters and genetic data from both nuclear and chloroplast markers. PMID- 26376817 TI - Anaerobic digestion of cattle offal: protein and lipid-rich substrate degradation and population dynamics of acidogens and methanogens. AB - Anaerobic digestion of cattle offal was investigated in batch reactors at 35 degrees C to determine the feasibility of using cattle offal as a feedstock. The organic content [i.e., volatile solids (VS)] of the cattle offal was mainly composed of protein (33.9%) and lipids (46.1%). Hydrolysis along with acidogenesis was monitored to investigate the substrate degradation and generation of intermediate products (e.g., volatile fatty acids, ammonia). Acetate (2.03 g/L), propionate (0.60 g/L), n-butyrate (0.39 g/L), and iso valerate (0.37 g/L) were major acidogenesis products (91% of total volatile fatty acid concentration). Overall protein and lipid degradation were 82.9 and 81.8%, respectively. Protein degraded first, and four times faster (0.28 day(-1)) than lipid (0.07 day(-1)). Methane yields were 0.52 L CH4/g VSadded and 0.65 L CH4/g VSremoved, indicating that anaerobic digestion of the offal was feasible. A quantitative QPCR assay was conducted to understand the microbial dynamics. The variation patt erns in the gene concentrations successfully indicated the population dynamics of proteolytic and lipolytic acidogens. A fourth-order Runge Kutta approximation was used to determine the kinetics of the acidogens. The molecular biotechnology approach was appropriate for the evaluation of the acidogenic biokinetics. The maximum growth rate, MU m, halfsaturation coefficients, K s, microbial yield coefficient, Y, cell mass decay rate coefficient, k d, of the proteolytic acidogens were 9.9 day(-1), 37.8 g protein/L, 1.1 * 10(10) copies/g protein, and 3.8 * 10(-1), respectively. Those for the lipolytic acidogens were 1.2 * 10(-1) day(-1), 8.3 g lipid/L, 1.5 * 10(9) copies/g lipid, and 9.9 * 10(-3) day(-1), respectively. PMID- 26376816 TI - A Cannabinoid Receptor 2 Agonist Prevents Thrombin-Induced Blood-Brain Barrier Damage via the Inhibition of Microglial Activation and Matrix Metalloproteinase Expression in Rats. AB - Thrombin mediates the life-threatening cerebral edema and blood-brain barrier (BBB) damage that occurs after intracerebral hemorrhage (ICH). We previously found that the selective cannabinoid receptor 2 (CB2R) agonist JWH-133 reduced brain edema and neurological deficits following germinal matrix hemorrhage (GMH). We explored whether CB2R stimulation ameliorated thrombin-induced brain edema and BBB permeability as well as the possible molecular mechanism involved. A total of 144 Sprague-Dawley (S-D) rats received a thrombin (20 U) injection in the right basal ganglia. JWH-133 (1.5 mg/kg) or SR-144528 (3.0 mg/kg) and vehicle were intraperitoneally (i.p.) injected 1 h after surgery. Brain water content measurement, Evans blue (EB) extravasation, Western blot, and immunofluorescence were used to study the effects of a CB2R agonist 24 h after surgery. The results demonstrated that JWH-133 administration significantly decreased thrombin-induced brain edema and reduced the number of Iba-1-positive microglia. JWH-133 also decreased the number of P44/P42(+)/Iba-1(+) microglia, lowered Evans blue extravasation, and inhibited the elevated matrix metallopeptidase (MMP)-9 and matrix metallopeptidase (MMP)-12 activities. However, a selective CB2R antagonist (SR-144528) reversed these effects. We demonstrated that CB2R stimulation reduced thrombin-induced brain edema and alleviated BBB damage. We also found that matrix metalloproteinase suppression may be partially involved in these processes. PMID- 26376818 TI - Sequential probing and dilatation in canalicular stenosis. AB - PURPOSE: To assess the usefulness of sequential probing for diagnosing lacrimal canalicular stenosis, and the effectiveness of bicanalicular silicone intubation after sequential dilatation in treatment. METHODS: Canalicular stenosis was diagnosed by sequential probing in 22 patients (22 eyes) who were misdiagnosed as canalicular obstruction. The patients were treated by bicanalicular silicone intubation after sequential dilatation. Anatomical improvements and functional relief of epiphora were evaluated. In addition, complications were evaluated. RESULTS: The average age of the 22 patients was 57 years, and the average follow up period was 13 months. The silicone tube was left in place for an average of 14 weeks. The anatomical success rate was 100 %. Fifty-four percent of patients achieved complete relief of epiphora, 32 % partial relief, and 14 % no relief. There were no complications. CONCLUSIONS: Sequential probing is an useful diagnostic method for canalicular stenosis. Bicanalicular silicone intubation after sequential dilatation is a simple and effective treatment, and could be performed as primary procedure for canalicular stenosis before invasive surgery. PMID- 26376819 TI - Uveal effusion syndrome mimicking severe chronic posterior uveitis: a case series of seven eyes of four patients. AB - PURPOSE: To describe the clinical findings and management of eyes affected by uveal effusion syndrome (UES) presenting with clinical features mimicking inflammatory ocular diseases, treated using individualized surgical approaches. METHODS: We report a consecutive interventional case series of seven eyes of four patients affected by UES. On presentation in our clinic, all patients showed signs of steroid effects as a consequence of a presumptive diagnosis; one eye had undergone vitrectomy for retinal detachment (RD), without benefit. Diagnosis of UES was based on ophthalmic examination, ultrasonography, fluorescein angiography, biometry and magnetic resonance imaging. Five eyes with active disease were treated using scleral thinning surgical procedures based on the extent and characteristics of the disease: sclerectomy sites were ultrasound guided to the area of maximal choroidal swelling, associated with evacuative puncture in the case of bilateral funnel-shaped RD. RESULTS: One patient was diagnosed with type 1 UES, two with type 2, and one with type 3. Mean postoperative follow-up was 26 months. In all eyes, surgery resolved the ciliochoroidal and retinal detachment and improved visual acuity. In two eyes, visual restoration was limited by a prolonged disease course. CONCLUSION: UES may be mistaken for other sources of ciliochoroidal effusion. Early diagnosis and treatment is critical to avoid unnecessary procedures and to prevent severe visual loss as a result of neuroretinal damage. Surgical treatment based on the extent and characteristics of the disease may be effective for the resolution of ciliochoroidal effusion, even in type 3 UES, where conventional surgery has proved unsuccessful. PMID- 26376820 TI - Letter to the editor: Forty-two-month outcome of intravitreal bevacizumab in myopic choroidal neovascularization. PMID- 26376821 TI - The effect of nocturnal CPAP therapy on the intraocular pressure of patients with sleep apnea syndrome. AB - PURPOSE: Few studies have documented that nocturnal continuous positive airway pressure (CPAP) therapy is associated with an increase in intraocular pressure (IOP) in patients with severe obstructive sleep apnea syndrome (OSAS). We re examined the effect of CPAP therapy on the IOP of OSAS patients. METHODS: The IOP of two different groups of newly diagnosed OSAS patients was compared at their first sleep lab exam without CPAP treatment (non-CPAP treated group; n = 20) and at the second sleep lab exam with CPAP treatment (CPAP treated group; n = 31). The sleep lab exam (sleep period: from 11:00 p.m. until 6:00 a.m.) included IOP measurements, a complete ophthalmologic exam, and nocturnal hemodynamic recordings. The IOP was measured serially using rebound tonometer (IOP; ICARE(r) PRO) performed while in sitting and supine positions before, during, and after the sleep period. We compared the difference in IOP of CPAP and non-CPAP groups. RESULTS: The mean IOP of the CPAP and non-CPAP groups measured in sitting position before the sleep period was 13.33 +/- 2.04 mmHg and 14.02 +/- 2.44 mmHg, respectively (p = 0.9). Assuming a supine position for 1 minute significantly increased the IOP by 1.93 mmHg and 2.13 mmHg for both the non-CPAP and CPAP groups (paired t-test; p = 0.02, p = 0.001 respectively), but this IOP rise showed no difference between the two groups. The IOP increased significantly further after 7 hours of sleep in the supine position, and the mean IOP of the CPAP and non-CPAP groups was 19.2 +/- 5.68 mmHg and 19.69 +/- 5.61 mmHg respectively (independent t-test; p = 0.74). The rise in IOP for both groups was not correlated with any hemodynamic parameters. Three OSAS patients with glaucoma treated with CPAP had mean IOP of 23.75 mmHg after 7 hours of sleep. CONCLUSIONS: OSAS patients have a significant rise in IOP during the sleep period when comparing measurements before and after the sleep period; however, CPAP therapy did not affect the measured IOP. The presented findings suggest that in terms of IOP, CPAP is safe for non-glaucomatous patients, but this may not hold true for glaucomatous patients. PMID- 26376823 TI - A rare presentation of hydropneumothorax in tropical pulmonary eosinophilia: cavitation and pneumonic consolidation in a child. AB - Tropical pulmonary eosinophilia (TPE) is a syndrome of wheezing, fever and eosinophilia seen predominantly in the Indian subcontinent and other tropical areas. The pathogenesis is due to an exaggerated immune response to the filarial antigens which includes type I, type III and type IV reactions with eosinophils playing a pivotal role. Leucocytosis with an absolute increase in eosinophils in the peripheral blood is the hallmark of TPE. Other criteria for the diagnosis of TPE include high titres of antifilarial antibodies, raised serum total IgE > 1000 ku/L and a favourable response to the antifilarial agent, diethyl-carbamazine. Although TPE runs a benign course, if left untreated, it could result in a fair degree of respiratory morbidity. PMID- 26376824 TI - Outcomes associated with ablation compared to combined ablation and transilluminated powered phlebectomy in the treatment of venous varicosities. AB - BACKGROUND: Patients with painful varicose veins and venous insufficiency can be treated by eliminating axial reflux only or by eliminating axial reflux plus phlebectomy with transilluminated powered phlebectomy. This study was undertaken with the aim of determining and improving signs and symptoms of venous disease (measured by venous clinical severity score) and complications (by routine surveillance ultrasound and long-term post-operative follow up) for each treatment strategy. METHODS: We performed a retrospective evaluation of prospectively collected data from 979 limbs undergoing procedures for significant varicose veins and venous insufficiency from March 2008 until June 2014 performed at a single tertiary referral hospital. Patient demographics, Clinical Etiology Anatomy and Pathophysiology classification, venous clinical severity scores pre- and post-procedure, treatment chosen, and peri-operative complications were collected; descriptive statistics were calculated and unadjusted surgical outcomes for patients stratified by the procedure performed. Multivariable logistic regression was used to evaluate the relationship between procedure type and thrombotic complications after adjusting for patient characteristics, severity of disease, pre-operative anticoagulation, and post-operative compression. RESULT: Venous clinical severity scores improved more with radiofrequency ablation + transilluminated powered phlebectomy as compared to radiofrequency ablation alone (3.8 +/- 3.4 vs. 3.2 +/- 3.1, p = 0.018). Regarding deep venous thrombosis, there was no significant difference between radiofrequency ablation + transilluminated powered phlebectomy vs. radiofrequency ablation alone. There was no statistical difference in asymptomatic endovenous heat-induced thrombosis or infection, although there were slightly more hematomas and cases of asymptomatic superficial thrombophlebitis with combined therapy. On multivariable analysis, only procedure type predicted thrombotic complications. CONCLUSION: Ablation of axial reflux plus transilluminated powered phlebectomy produces improved outcomes as measured by venous clinical severity score, with slight increases in minor post-operative complications and should be strongly considered as initial therapy when patients present with significant symptomatic varicose veins and superficial venous insufficiency. Implementation of a standardized thromboprophylaxis protocol with individual risk assessment results in few significant thrombotic complications amongst high-risk patients, thus potentially obviating the need for routine post-operative duplex. PMID- 26376822 TI - Impact of post-colposcopy management on women's long-term worries: results from the UK population-based TOMBOLA trial. AB - BACKGROUND: Effective cervical screening reduces cancer incidence and mortality. However, these benefits may be accompanied by some harms, potentially including, adverse psychological impacts. Studies suggest women may have concerns about various specific issues, such as cervical cancer. AIM: To compare worries about cervical cancer, future fertility, having sex, and general health between women managed by alternative policies at colposcopy. DESIGN: Multicentre individually randomised controlled trial, nested within the National Health Service Cervical Screening Programmes. SETTING: UK. METHODS: 1515 women, aged 20-59 years, with low-grade cytology who attended colposcopy during February 2001-October 2002, were randomised to immediate loop excision or punch biopsies with recall for treatment if cervical intraepithelial neoplasia (CIN)2/3 was confirmed. Women completed questionnaires at recruitment and after 12, 18, 24 and 30 months. Outcomes were prevalence of worries at each time-point (point prevalence) and at any time-point during follow-up (12-30 months; cumulative prevalence). Primary analysis was by intention-to-treat (ITT); secondary per-protocol analysis compared groups according to management received among women with an abnormal transformation zone. RESULTS: Cumulative prevalence of worries was: cervical cancer 40%; having sex 26%, future fertility 24%, and general health 60%. In ITT analyses, there were no statistically significant differences between management arms in cumulative or point prevalence of any of the worries. In per-protocol analyses, between-group differences were significant only for future fertility; cumulative prevalence was highest in women who underwent punch biopsies and treatment. CONCLUSIONS: There is no difference in the prevalence of specific worries in women randomised to alternative post-colposcopy management policies. CLINICAL TRIAL REGISTRATION: ISRCTN: 34841617. PMID- 26376825 TI - Serum interleukin-6 level as an early marker of injury severity in trauma patients in an urban low-income setting: a cross-sectional study. AB - BACKGROUND: Trauma is still the leading cause of death in many regions of the world. Severity scores have been developed to assist in management of trauma victims. Immune response to trauma has been known to positively correspond to the severity of trauma. Part of this response involves release of cytokines into blood circulation which promote the acute inflammatory response commonly seen after trauma. Studies have shown that IL-6 levels commonly correlate positively with the Injury Severity Score (ISS). The aim of this cross-sectional study was to determine whether this kind of relationship exists between IL-6 levels and injury severity in trauma patients in Mulago Hospital as defined by the Kampala Trauma Score (KTSII) which is locally developed. METHODS: Trauma patients aged >=18 years presenting to the Accident and Emergency unit of Mulago National Referral Hospital (MNRH) within 12 h after injury were recruited into the study after obtaining consent. Severity of injury was determined as per the Kampala Trauma Score (KTSII) and venous blood drawn for assay of serum IL-6 levels. Data obtained was entered and analyzed using Stata version 11 software focusing on the association between Serum IL-6 levels with Severity of trauma and duration of injury. RESULTS: A total of 159 patients were recruited (79 Mild and 80 Severe trauma) with a male to female ratio of 4.7:1. Road traffic crashes (67.92%) were the commonest cause of injury. Serum IL-6 levels were found to positively correspond with severity of injury (z = 4.718, p < 0.001). There was no significant correlation between serum IL-6 levels and duration of injury in both severe (r = 0.12, p = 0.29) and mild (r = 0.06, p = 0.62) trauma groups of patients. Only 9.43% of trauma patients were brought in an Ambulance. CONCLUSIONS: Serum IL-6 levels correspond with severity of injury. However, within the first twelve hours after injury, these levels did not vary significantly with duration of injury. PMID- 26376826 TI - Transforming growth factor-beta-sphingosine kinase 1/S1P signaling upregulates microRNA-21 to promote fibrosis in renal tubular epithelial cells. AB - Renal fibrosis is a progressive pathological change characterized by tubular cell apoptosis, tubulointerstitial fibroblast proliferation, and excessive deposition of extracellular matrix (ECM). miR-21 has been implicated in transforming growth factor-beta (TGF-beta)-stimulated tissue fibrosis. Recent studies showed that sphingosine kinase/sphingosine-1-phosphate (SphK/S1P) are also critical for TGF beta-stimulated tissue fibrosis; however, it is not clear whether SphK/S1P interacts with miR-21 or not. In this study, we hypothesized that SphK/S1P signaling is linked to upregulation of miR-21 by TGF-beta. To verify this hypothesis, we first determined that miR-21 was highly expressed in renal tubular epithelial cells (TECs) stimulated with TGF-beta by using qRT-PCR and Northern blotting. Simultaneously, inhibition of miR-21, mediated by the corresponding antimir, markedly decreased the expression and deposition of type I collagen, fibronectin (Fn), cysteine-rich protein 61 (CCN1), alpha-smooth muscle actin, and fibroblast-specific protein1 in TGF-beta-treated TECs. ELISA and qRT-PCR were used to measure the S1P and SphK1 levels in TECs. S1P production was induced by TGF-beta through activation of SphK1. Furthermore, it was observed that TGF-beta stimulated upregulation of miR-21 was abolished by SphK1 siRNA and was restored by the addition of exogenous S1P. Blocking S1PR2 also inhibited upregulation of miR-21. Additionally, miR-21 overexpression attenuated the repression of TGF-beta stimulated ECM deposition and epithelial-mesenchymal transition by SphK1 and S1PR2 siRNA. In summary, our study demonstrates a link between SphK1/S1P and TGF beta-induced miR-21 in renal TECs and may represent a novel therapeutic target in renal fibrosis. PMID- 26376827 TI - Inclusion body myositis in a patient with chronic myeloid leukemia treated with dasatinib: a case report. AB - INTRODUCTION: Chronic myelogenous leukemia is often treated using tyrosine kinase inhibitors such as dasatinib. Here we describe a rare case of inflammatory myopathy in a patient with chronic myelogenous leukemia treated with the tyrosine kinase inhibitor dasatinib. CASE PRESENTATION: A 69-year-old Caucasian man with imatinib-resistant chronic myelogenous leukemia achieved complete molecular remission in response to dasatinib therapy. However, from a normal initial serum creatine kinase level, he developed elevated serum creatine kinase levels and gradual-onset progressive muscle weakness after dasatinib therapy was initiated. Our patient was eventually diagnosed with inclusion body myositis. However, we were unable to determine the mechanism underlying the dasatinib-associated muscle weakness. Given the efficacy of dasatinib in the treatment of chronic myelogenous leukemia and our patient's mild symptoms of inclusion body myositis, he continued to receive dasatinib under close clinical and laboratory observation. CONCLUSION: Despite the wide use of dasatinib and its documented safety, we report a case of severe muscle injury of unknown etiology. Therefore, patients with chronic myelogenous leukemia receiving dasatinib and perhaps all tyrosine kinase inhibitors should be carefully monitored for signs of muscle injury, especially if this is associated with significant elevations in serum creatine kinase levels. PMID- 26376828 TI - Detection of immunological treatment failure among HIV infected patients in Ethiopia: a retrospective cohort study. AB - BACKGROUND: Timely detection of treatment failure with subsequent switch to second-line regimen reduces mortality among HIV infected people on antiretroviral therapy (ART). This paper aims to investigate the detection of immunological treatment failure and switch rate to second line regimen in Ethiopia. METHODS: A retrospective cohort study was conducted among HIV infected patients (age > 15 years) who initiated ART between 2007 and 2009. The required data were collected from patient registers and formats. Data were entered and validated using EpiData software and then exported to SPSS version 20.0 for analysis. Odds ratio with 95% CI was used to assess whether immunological treatment failure was associated with experiencing unfavorable treatment outcomes (death or lost to follow up). RESULTS: Records of 293 patients were reviewed with a total of 1545 Person-Years of Observation (PYO). The median baseline CD4 count was 115 cells/mm(3) (IQR: 64 176). A total of 46 (15.7%) patients experienced immunological treatment failure. The immunological failure rate was 3.0 per 100 PYO. Treatment was switched to second-line regimen for six (2.1%) patients. The rate of treatment switch to second-line regimen for any purpose was 0.4 per 100 PYO. Out of the six patients, only two fulfilled the WHO criteria for immunological failure; the remaining four patients had their treatment switched to second-line regimen for other purposes. This implies that only 4.3% (2/46) of patients with immunological failure were switched to second-line regimen. The risk of experiencing unfavorable outcome was 5.75 (95% CI 1.11, 29.8) times higher among those who had immunological failure than their counterparts after adjusting for baseline CD4 count. CONCLUSIONS: Majority of patients with immunological treatment failures were not detected and continued taking the failed regimen. Further studies are required to assess and explore why patients with immunological failure are not switched to second-line regimen as per the standard protocol. PMID- 26376829 TI - Ratiometric oxygen sensing using lanthanide luminescent emitting interfaces. AB - Herein we describe the first example of a ratiometric lanthanide luminescent oxygen sensing interface. Immobilisation of terbium and europium cyclen complexes on glass substrates was achieved by a novel aryl nitrene photografting approach. The resulting interfaces demonstrated a ratiometric oxygen response between 0 and 0.2 atm partial oxygen pressure. PMID- 26376831 TI - Controlled growth of silica-titania hybrid functional nanoparticles through a multistep microfluidic approach. AB - Silica/titania-based functional nanoparticles were prepared through controlled nucleation of titania and subsequent encapsulation by silica through a multistep microfluidic approach, which was successfully applied to obtaining aminopropyl functionalized silica/titania nanoparticles for a highly sensitive humidity sensor. PMID- 26376830 TI - Impact of pharmacist intervention on adherence and measurable patient outcomes among depressed patients: a randomised controlled study. AB - BACKGROUND: Adherence to antidepressant treatment is essential for the effective management of patients with major depressive disorder. Adherence to medication is a dynamic decision-making process, and pharmacists play an important role in improving adherence to antidepressant treatment in different settings within the healthcare system. The aim of this study was to assess whether pharmacist interventions based on shared decision making improved adherence and patient related outcomes. METHODS: This was a randomised controlled study with a 6-month follow-up. Participants were randomly allocated to two groups: 1) intervention group (IG) (usual pharmacy services plus pharmacist interventions based on shared decision making); or 2) control group (CG) (usual pharmacy services). Recruited patients fulfilled the following inclusion criteria: aged 18 to 60 years diagnosed with a major depressive disorder, and no history of psychosis or bipolar disorders. A research assistant blinded to the group allocations collected all data. RESULTS: Two hundred and thirty-nine patients met the inclusion criteria and were randomised to the IG (n = 119) or CG (n = 120). Nineteen patients dropped out of the study during the follow-up phase. After 6 months, patients in the IG had significantly more favorable medication adherence, treatment satisfaction, general overuse beliefs, and specific concern beliefs. However, the groups did not differ in severity of depression or health-related quality of life after 6 months. CONCLUSIONS: Our findings emphasise the important role of pharmacists in providing direct patient care in regular pharmacy practice to improve adherence to medications and other patient-reported outcomes. TRIAL REGISTRATION: ISRCTN34879893, Date assigned: 30/12/2014. PMID- 26376832 TI - Characteristics Associated with Sleep Duration, Chronotype, and Social Jet Lag in Adolescents. AB - Sleep is a complex behavior with numerous health implications. Identifying sociodemographic and behavioral characteristics of sleep is important for determining those at greatest risk for sleep-related health disparities. In this cross-sectional study, general linear models were used to examine sociodemographic and behavioral characteristics associated with sleep duration, chronotype, and social jet lag in adolescents. One hundred and fifteen participants completed Phase I (self-reported sleep measures), and 69 of these participants completed Phase II (actigraphy-estimated sleep measures). Black adolescents had shorter free night sleep than Hispanics. Youth with later chronotypes ate fewer fruits and vegetables, drank more soda, were less physically active, and took more daytime naps. Based on these findings, recommendations for individual support and school policies are provided. PMID- 26376833 TI - Downgraded Lymphoma: B-Chronic Lymphocytic Leukemia in a Known Case of Diffuse Large B-Cell Lymphoma--De Novo Occurrence or Transformation. PMID- 26376834 TI - BAP1 facilitates diagnostic objectivity, classification, and prognostication in malignant pleural mesothelioma. AB - BRCA-associated protein 1 (BAP1) has emerged as a promising biomarker for malignant pleural mesothelioma (MPM). Loss of BAP1 expression can occur by a variety of mechanisms, but reports on incidence are variable and the clinical significance is unclear. In order to investigate the diagnostic and prognostic significance of BAP1, we constructed a tissue microarray consisting of 111 MPM cases and performed BAP1 immunohistochemistry. BAP1 was lost in 77% of epithelioid cases (n=58) but was retained in all sarcomatoid cases (n=10); 49% of biphasic cases showed loss (n=43), and BAP1-negative cases demonstrated loss of staining in both the epithelioid and sarcomatoid components. All non-neoplastic mesothelial tissues (n=20) retained BAP1, resulting in a sensitivity, specificity, positive predictive value, and negative predictive value of 61%, 100%, 100%, and 32%, respectively. Moreover, BAP1 expression in spindled mesothelium enabled discrimination of reactive and malignant cells, thus providing a more objective means of distinguishing epithelioid from biphasic morphology compared to histology alone. Nonetheless, BAP1 staining was patchy in some benign mesothelial neoplasms, which raises concern for using BAP1 in small biopsies. Kaplan-Meier analysis demonstrated a significant improvement in overall survival with BAP1 loss, but this did not reach significance in multivariate analysis accounting for histologic subtype. When only epithelioid cases were analyzed there was a trend toward increased survival, but it did not reach significance. We conclude that BAP1 loss is frequent in epithelioid MPM, which is in turn associated with improved survival, and that it can have additional clinical significance by facilitating histologic classification. PMID- 26376835 TI - [Mycobacterium bovis in wildlife of the dairy regions of Santa Fe (Argentina)]. AB - Control eradication campaigns of bovine tuberculosis based on the "test and slaughter" approach were successful in many countries and regions; however, in some areas the infection persists and one of the main reasons is Mycobacterium bovis infection in wild life species. Argentina has applied the same approach since 1999, achieving progress in dairy cattle herds. Nonetheless, the wildlife role has never been investigated. The objective of this study was to determine if wildlife from the Santa Fe dairy area is infected with M. bovis. Wildlife species having a positive tuberculin skin test were captured in five dairy farms. Ninety five wildlife mammals were captured; M. bovis was recovered from 7 possums (Didelphys albiventris), from one fox (Lycolapex gimnocercus) and from one rat (Rattus norvegicus). None of the animals exhibited macroscopic lesions. The most frequently isolated M. bovis spoligotypes were types 34 (4 isolates) and 12 (3 isolates). Spoligotype 34 is the most frequently isolated type in Argentine cattle. The role of D. albiventris as spillover host of M. bovis is discussed in this study. PMID- 26376836 TI - Resonant Raman scattering of ZnSxSe1-x solid solutions: the role of S and Se electronic states. AB - A comprehensive Raman resonance scattering study of ZnSxSe1-x (ZnSSe) solid solutions over the whole compositional range (0 <= x <= 1) has been carried out using 325 and 455 nm excitation wavelengths. The Raman scattering intensities of LO ZnS-like and ZnSe-like phonon modes, corresponding to pure S and Se vibrations, respectively, are revealed to be significantly enhanced when excited with 325 nm excitation in the case of S vibrations, and with 455 nm in the case of Se vibrations. This behavior is explained by the interaction of the excitation photons with the corresponding S or Se electronic states in the conduction band, and further confirmed by first principles simulations. These findings advance the fundamental understanding of the coupling between the electronic transitions and photons in the case of Raman resonance effects, and provide inputs for further studies of lattice dynamics, especially in the case of chalcogenide materials. Additionally, the coexistence of modes corresponding to only S vibrations and only Se vibrations in the ZnSSe alloys makes these results applicable for the compositional assessment of ZnSSe compounds. PMID- 26376837 TI - Mechanically strong triple network hydrogels based on hyaluronan and poly(N,N dimethylacrylamide). AB - Hyaluronan (HA) is a natural polyelectrolyte with distinctive biological functions. Cross-linking of HA to generate less degradable hydrogels for use in biomedical applications has attracted interest over many years. One limitation of HA hydrogels is that they are very brittle and/or easily dissolve in physiological environments, which limit their use in load-bearing applications. Herein, we describe the preparation of triple-network (TN) hydrogels based on HA and poly(N,N-dimethylacrylamide) (PDMA) of high mechanical strength by sequential gelation reactions. TN hydrogels containing 81-91% water sustain compressive stresses above 20 MPa and exhibit Young's moduli of up to 1 MPa. HA of various degrees of methacrylation was used as a multifunctional macromer for the synthesis of the brittle first-network component, while loosely cross-linked PDMA was used as the ductile, second and third network components of TN hydrogels. By tuning the methacrylation degree of HA, double-network hydrogels with a fracture stress above 10 MPa and a fracture strain of 96% were obtained. Increasing the ratio of ductile-to-brittle components via the TN approach further increases the fracture stress above 20 MPa. Cyclic mechanical tests show that, although TN hydrogels internally fracture even under small strain, the ductile components hinder macroscopic crack propagation by keeping the macroscopic gel samples together. PMID- 26376838 TI - Injuries in male professional football: A prospective comparison between individual and team-based exposure registration. AB - Methodological considerations of football injury epidemiology have only scarcely been described. The aim of this study was to evaluate the inter-rater agreement in injury capture rate and injury categorization for data registered in two different prospective injury surveillance audits studying the same two Norwegian male professional football clubs for two consecutive seasons, 2008-2009. One audit used team-based exposure (TBE) recording and the other individual-based exposure (IBE). The number of injuries recorded and corresponding injury rates (injuries/1000 h exposure) were compared between audits. Cohen's kappa and prevalence-adjusted bias-adjusted kappa (PABAK) coefficients were calculated for injury variables. Of 323 injuries included, the IBE audit captured 318 (overall capture rate 98.5%, training 98.9%, match 97.8%) and the TBE audit 303 injuries (overall capture rate 93.8%, training 91.4%, match 97.1%). Agreement analysis showed kappa and PABAK coefficients regarded as almost perfect (> 0.81) for 8 of 9 injury variables, and substantial (k 0.75) for the variable injury severity. In conclusion, the capture rate for training injuries was slightly higher with IBE recording, and inter-agreement in injury categorization was very high. PMID- 26376839 TI - Decrease in autoantibody titres during long-term treatment of scleroderma with rituximab: a promising surveillance marker of therapy? PMID- 26376840 TI - Optimization of dose of collagen hydrolysate to prevent UVB-irradiated skin damage. AB - Collagen hydrolysate (CH) was orally administered to UVB-irradiated hairless mice at doses of 20, 200-2000 mg/kg BW/day. The low dose of CH increased the skin hydration and reduced the transepidermal water loss on damaged skin. These results suggested the optimal dose of collagen to improve the UV-damaged skin condition. PMID- 26376842 TI - B7-H3 protein expression in acute myeloid leukemia. AB - Costimulatory molecules are essential regulators of the immunological synapse and enable the fine-tuning of the immune response. These mechanisms are subverted by cancer cells to evade immunosurveillance. The B7 family of costimulatory molecules comprises several ligands that may contribute to immunoescape. B7-H3 [B7-homolog 3 or CD276] remains poorly investigated in hematological malignancies. To determine the role B7-H3, we analyzed the expression of this molecule in blast cells from a cohort of 111 acute myeloid leukemia (AML) patients. B7-H3 was expressed in blast cells with a mean fluorescence intensity ratio >3 in 30 (27%) of the 111 patients. B7-H3 expression was higher in the M3 and M5 FAB subtypes and in cases with mutated NPM1 and wild type CEBPA. There were no significant differences found for the FLT3-ITD or cytogenetic risk groups. The complete remission (CR) rate between the 17 B7-H3-positive and 58 negative patients who were treated intensively was not different. The event free survival was longer in B7-H3-positive patients (P = 0.014), and there was a trend toward better overall survival. However, this difference was not statistically significant (P = 0.053). In conclusion, B7-H3 is one of the most strongly expressed B7-family molecules in AML and merits further investigation. PMID- 26376841 TI - Inter-Method Performance Study of Tumor Volumetry Assessment on Computed Tomography Test-Retest Data. AB - RATIONALE AND OBJECTIVES: Tumor volume change has potential as a biomarker for diagnosis, therapy planning, and treatment response. Precision was evaluated and compared among semiautomated lung tumor volume measurement algorithms from clinical thoracic computed tomography data sets. The results inform approaches and testing requirements for establishing conformance with the Quantitative Imaging Biomarker Alliance (QIBA) Computed Tomography Volumetry Profile. MATERIALS AND METHODS: Industry and academic groups participated in a challenge study. Intra-algorithm repeatability and inter-algorithm reproducibility were estimated. Relative magnitudes of various sources of variability were estimated using a linear mixed effects model. Segmentation boundaries were compared to provide a basis on which to optimize algorithm performance for developers. RESULTS: Intra-algorithm repeatability ranged from 13% (best performing) to 100% (least performing), with most algorithms demonstrating improved repeatability as the tumor size increased. Inter-algorithm reproducibility was determined in three partitions and was found to be 58% for the four best performing groups, 70% for the set of groups meeting repeatability requirements, and 84% when all groups but the least performer were included. The best performing partition performed markedly better on tumors with equivalent diameters greater than 40 mm. Larger tumors benefitted by human editing but smaller tumors did not. One-fifth to one half of the total variability came from sources independent of the algorithms. Segmentation boundaries differed substantially, not ony in overall volume but also in detail. CONCLUSIONS: Nine of the 12 participating algorithms pass precision requirements similar to what is indicated in the QIBA Profile, with the caveat that the present study was not designed to explicitly evaluate algorithm profile conformance. Change in tumor volume can be measured with confidence to within +/-14% using any of these nine algorithms on tumor sizes greater than 10 mm. No partition of the algorithms was able to meet the QIBA requirements for interchangeability down to 10 mm, although the partition comprising best performing algorithms did meet this requirement for a tumor size of greater than approximately 40 mm. PMID- 26376844 TI - Immunotherapies in Early and Advanced Renal Cell Cancer. AB - The development of new immunomodulatory monoclonal antibodies targeting the CTLA 4 or PD-1 axis has led to a revival of research on immunotherapies in solid tumours including renal cell cancer (RCC). The initial results observed with these monoclonal antibodies in the treatment of advanced melanoma have resulted in considerable interest in this treatment strategy in all tumour types. Preliminary data of these new antibodies in advanced RCC are promising and they have good safety profiles. Response rates are low but durable tumour control has been observed in some patients. However, at the moment there is no evidence that targeting the CTLA-4 or PD-1 axis provides a substantial clinical benefit compared to established treatment with tyrosine kinase or mTOR inhibitors. There are also no reliable predictive markers. At the moment, several randomised trials have been initiated to investigate the new immunomodulatory antibodies either as single agents or in combination with anti-VEGF targeted therapy. Vaccines have continued to be investigated in advanced and adjuvant settings. No trial has so far established vaccines as a standard treatment in either situation. There are still large randomised trials ongoing investigating the potential benefit of a vaccine in combination with standard tyrosine kinase inhibitor therapy. In this chapter we will summarise selected studies on immunotherapy in advanced RCC with a focus on anti-PD-1, anti-PD-L1, and anti-CTLA-4 antibodies. We will also touch briefly on the adjuvant situation and tumour vaccines. PMID- 26376843 TI - Radio-photothermal therapy mediated by a single compartment nanoplatform depletes tumor initiating cells and reduces lung metastasis in the orthotopic 4T1 breast tumor model. AB - Tumor Initiating Cells (TICs) are resistant to radiotherapy and chemotherapy, and are believed to be responsible for tumor recurrence and metastasis. Combination therapies can overcome the limitation of conventional cancer treatments, and have demonstrated promising application in the clinic. Here, we show that dual modality radiotherapy (RT) and photothermal therapy (PTT) mediated by a single compartment nanosystem copper-64-labeled copper sulfide nanoparticles ([(64)Cu]CuS NPs) could suppress breast tumor metastasis through eradication of TICs. Positron electron tomography (PET) imaging and biodistribution studies showed that more than 90% of [(64)Cu]CuS NPs was retained in subcutaneously grown BT474 breast tumor 24 h after intratumoral (i.t.) injection, indicating the NPs are suitable for the combination therapy. Combined RT/PTT therapy resulted in significant tumor growth delay in the subcutaneous BT474 breast cancer model. Moreover, RT/PTT treatment significantly prolonged the survival of mice bearing orthotopic 4T1 breast tumors compared to no treatment, RT alone, or PTT alone. The RT/PTT combination therapy significantly reduced the number of tumor nodules in the lung and the formation of tumor mammospheres from treated 4T1 tumors. No obvious side effects of the CuS NPs were noted in the treated mice in a pilot toxicity study. Taken together, our data support the feasibility of a therapeutic approach for the suppression of tumor metastasis through localized RT/PTT therapy. PMID- 26376845 TI - Highly Regio- and Enantioselective Alkoxycarbonylative Amination of Terminal Allenes Catalyzed by a Spiroketal-Based Diphosphine/Pd(II) Complex. AB - An enantioselective alkoxycarbonylation-amination cascade process of terminal allenes with CO, methanol, and arylamines has been developed. It proceeds under mild conditions (room temperature, ambient pressure CO) via oxidative Pd(II) catalysis using an aromatic spiroketal-based diphosphine (SKP) as a chiral ligand and a Cu(II) salt as an oxidant and affords a wide range of alpha-methylene-beta arylamino acid esters (36 examples) in good yields with excellent enantioselectivity (up to 96% ee) and high regioselectivity (branched/linear > 92:8). Preliminary mechanistic studies suggested that the reaction is likely to proceed through alkoxycarbonylpalladation of the allene followed by an amination process. The synthetic utility of the protocol is showcased in the asymmetric construction of a cycloheptene-fused chiral beta-lactam. PMID- 26376846 TI - Association between serum adropin levels and gestational diabetes mellitus; a case-control study. AB - Gestational diabetes mellitus (GDM) is increasing worldwide. The aim of this study was to investigate the association between serum adropin concentration and GDM. In a case-control study, conducted in 2013, 40 pregnant women with GDM and 40 healthy pregnant women (controls) were evaluated. Fasting serum adropin and lipid concentration were measured during 24th-28th weeks of gestation for both groups. These factors were compared between the two groups using independent sample t-test. There was a significant difference in adropin levels between the two groups and mean adropin levels were lower in GDM group (p: 0.016). There was no significant correlation between serum adropin levels and body mass index as well as fasting blood glucose (FBS) or serum lipid profile including high-density lipoprotein, low-density lipoprotein, cholesterol and triglyceride concentration (p > 0.05). There was a significant association between adropin concentration and GDM even after using regression model for removing confounding factors (odds ratio = 0.681). Low serum adropin concentration is associated with GDM in Iranian pregnant women. PMID- 26376847 TI - Electroacupuncture ameliorates cognitive impairment and regulates the expression of apoptosis-related genes Bcl-2 and Bax in rats with cerebral ischaemia reperfusion injury. AB - BACKGROUND: Post-stroke cognitive impairment seriously affects the quality of life and functional rehabilitation of patients with stroke. OBJECTIVE: To examine the effects of electroacupuncture (EA) at GV20 and GV24 on cognitive impairment and apoptosis including expression of apoptosis-related genes Bcl-2 and Bax in a rat model of cerebral ischaemia-reperfusion (IR) induced by middle cerebral artery occlusion (MCAO). METHODS: Thirty-five Sprague-Dawley rats were allocated to a sham operation control group (SC group, n=10) or underwent surgery and MCAO (n=25). Postoperatively the latter group was randomly subdivided into EA or untreated (IR) groups. Cognitive impairment was assessed using the Morris water maze (MWM). Apoptosis was examined by detection of Bcl-2 and Bax expression in the cerebral cortex. RESULTS: The EA group had significantly decreased neurological deficit scores compared to the IR group (p<0.05). In the MWM test, significant differences in escape latency and route were observed between the EA and IR groups (p<0.05). Rats in the EA group performed better in the probe trial than those in the IR group (p<0.05). EA treatment markedly reduced the number of TUNEL-positive cells compared to the IR group (20.13+/-4.30% vs 38.40+/-3.38%; p<0.001). Reverse transcription-polymerase chain reaction (RT-PCR) results showed the Bcl-2/Bax ratio was significantly increased in the EA group compared to the IR group (1.61+/-0.19 vs 0.50+/-0.05, p<0.01). CONCLUSIONS: These findings suggest that EA ameliorates cognitive impairment of rats with IR injury by modulating Bcl-2 and Bax expression. PMID- 26376848 TI - Acupuncture effects under anaesthesia and questions about placebo. PMID- 26376849 TI - Vitamin D deficiency exacerbates COPD-like characteristics in the lungs of cigarette smoke-exposed mice. AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by excessive inflammation and disturbed bacterial clearance in the airways. Although cigarette smoke (CS) exposure poses a major risk, vitamin D deficiency could potentially contribute to COPD progression. Many in vitro studies demonstrate important anti-inflammatory and antibacterial effects of vitamin D, but a direct contribution of vitamin D deficiency to COPD onset and disease progression has not been explored. METHODS: In the current study, we used a murine experimental model to investigate the combined effect of vitamin D deficiency and CS exposure on the development of COPD-like characteristics. Therefore, vitamin D deficient or control mice were exposed to CS or ambient air for a period of 6 (subacute) or 12 weeks (chronic). Besides lung function and structure measurements, we performed an in depth analysis of the size and composition of the cellular infiltrate in the airways and lung parenchyma and tested the ex vivo phagocytic and oxidative burst capacity of alveolar macrophages. RESULTS: Vitamin D deficient mice exhibited an accelerated lung function decline following CS exposure compared to control mice. Furthermore, early signs of emphysema were only observed in CS-exposed vitamin D deficient mice, which was accompanied by elevated levels of MMP-12 in the lung. Vitamin D deficient mice showed exacerbated infiltration of inflammatory cells in the airways and lung parenchyma after both subacute and chronic CS exposure compared to control mice. Furthermore, elevated levels of typical proinflammatory cytokines and chemokines could be detected in the bronchoalveolar lavage fluid (KC and TNF-alpha) and lung tissue (IP-10, MCP-1, IL-12) of CS-exposed vitamin D deficient mice compared to control mice. Finally, although CS greatly impaired the ex vivo phagocytic and oxidative burst function of alveolar macrophages, vitamin D deficient mice did not feature an additional defect. CONCLUSIONS: Our data demonstrate that vitamin D deficiency both accelerates and aggravates the development of characteristic disease features of COPD. As vitamin D deficiency is highly prevalent, large randomized trials exploring effects of vitamin D supplementation on lung function decline and COPD onset are needed. PMID- 26376850 TI - Identification of serum proteome signatures of locally advanced and metastatic gastric cancer: a pilot study. AB - BACKGROUND: The gastric cancer is one of the most common and mortal cancer worldwide. The initial asymptomatic development and further nonspecific symptoms result in diagnosis at the advanced stage with poor prognosis. Yet, no clinically useful biomarkers are available for this malignancy, and invasive gastrointestinal endoscopy remains the only reliable option at the moment. Hence, there is a need for discovery of clinically useful noninvasive diagnostic and/or prognostic tool as an alternative (or complement) for current diagnostic tools. Here we aimed to search for serum proteins characteristic for local and invasive gastric cancer. METHODS: Pre-treatment blood samples were collected from patients with diagnosed gastric adenocarcinoma at the different stage of disease: 35 patients with locally advanced cancer and 18 patients with metastatic cancer; 50 healthy donors were also included as a control group. The low-molecular-weight fraction of serum proteome (i.e., endogenous peptidome) was profiled by the MALDI ToF mass spectrometry, and the whole proteome components were identified and quantified by the LC-MS/MS shotgun approach. RESULTS: Multicomponent peptidome signatures were revealed that allowed good discrimination between healthy controls and cancer patients, as well as between patients with locally advanced and metastatic cancer. Moreover, a LC-MS/MS approach revealed 49 serum proteins with different abundances between healthy donors and cancer patients (predominantly proteins associated with inflammation and acute phase response). Furthermore, 19 serum proteins with different abundances between patients with locally advanced and metastatic cancer were identified (including proteins associated with cytokine/chemokine response and metabolism of nucleic acids). However, neither peptidome profiling nor shotgun proteomics approach allowed detecting serum components discriminating between two subgroups of patients with local disease who either developed or did not develop metastases during follow up. CONCLUSIONS: The molecular differences between locally advanced and metastatic gastric cancer, as well as more obvious differences between healthy individuals and cancer patients, have marked reflection at the level of serum proteome. However, we have no evidence that features of pre-treatment serum proteome could predict a risk of cancer dissemination in patients treated due to local disease. Nevertheless, presented data confirmed potential applicability of a serum proteome signature-based biomarker in diagnostics of gastric cancer. PMID- 26376851 TI - The waiting time problem in a model hominin population. AB - BACKGROUND: Functional information is normally communicated using specific, context-dependent strings of symbolic characters. This is true within the human realm (texts and computer programs), and also within the biological realm (nucleic acids and proteins). In biology, strings of nucleotides encode much of the information within living cells. How do such information-bearing nucleotide strings arise and become established? METHODS: This paper uses comprehensive numerical simulation to understand what types of nucleotide strings can realistically be established via the mutation/selection process, given a reasonable timeframe. The program Mendel's Accountant realistically simulates the mutation/selection process, and was modified so that a starting string of nucleotides could be specified, and a corresponding target string of nucleotides could be specified. We simulated a classic pre-human hominin population of at least 10,000 individuals, with a generation time of 20 years, and with very strong selection (50% selective elimination). Random point mutations were generated within the starting string. Whenever an instance of the target string arose, all individuals carrying the target string were assigned a specified reproductive advantage. When natural selection had successfully amplified an instance of the target string to the point of fixation, the experiment was halted, and the waiting time statistics were tabulated. Using this methodology we tested the effect of mutation rate, string length, fitness benefit, and population size on waiting time to fixation. RESULTS: Biologically realistic numerical simulations revealed that a population of this type required inordinately long waiting times to establish even the shortest nucleotide strings. To establish a string of two nucleotides required on average 84 million years. To establish a string of five nucleotides required on average 2 billion years. We found that waiting times were reduced by higher mutation rates, stronger fitness benefits, and larger population sizes. However, even using the most generous feasible parameters settings, the waiting time required to establish any specific nucleotide string within this type of population was consistently prohibitive. CONCLUSION: We show that the waiting time problem is a significant constraint on the macroevolution of the classic hominin population. Routine establishment of specific beneficial strings of two or more nucleotides becomes very problematic. PMID- 26376852 TI - Value of positron emission tomography in diagnosing synchronous penile metastasis from urothelial bladder cancer. AB - Metastases to the penis are extremely rare events. Most frequently, penile metastases come from the urogenital system (bladder, prostate) or the rectum sigmoid colon. Usually painful, penile lesions may be asymptomatic, making diagnosis more challenging. Hence, we report the adding value of (18)F fludeoxyglucose-positron emission tomography/computed tomography ((18)F-FDG PET/CT) in the detection of penile metastases originating from urothelial carcinoma of the bladder. Arguably, penile metastases must be considered as an advanced disease requiring essentially palliative care. Therefore, accurate staging of clinically localized muscle-invasive bladder cancer is crucial to avoid useless curative intent radical surgery. PMID- 26376853 TI - Development and feasibility of an automated call monitoring intervention for older wheelchair users: the MOvIT project. AB - BACKGROUND: Recent advances in wheeled mobility technology are multiplying opportunities for community integration and improved quality of life. The mobility needs of older wheelchair users are particularly complex due to a constellation of chronic conditions and comorbidities that may compromise optimal use of the device. The purpose of the Mobility Outcomes via Information Technologies (MOvIT) project is to examine the feasibility of automated calls for the systematic monitoring for adverse outcomes associated with wheelchair use. METHODS: A two-phase mixed methods approach was used. Phase I involved user centered development and face validation of a monitoring questionnaire with end users (seven wheelchair users and five healthcare providers). Phase II tested the feasibility of monitoring outcomes using automated calls to administer the MOvIT questionnaire 1 and 3 months after wheelchair delivery with a prospective cohort of older adults (50-84 years of age). When problems were identified, the computer monitoring system notified a clinical coordinator who followed up with respondents requiring interventions. Feasibility data were extracted from the web database and from individual interviews covering perceived ease of use, usefulness and intention to use the MOvIT questionnaire in the future. RESULTS: The MOvIT monitoring questionnaire developed in phase I tracks nine potential wheelchair-related adverse outcomes considered important for end-users: 1) non use of wheelchair, 2) pain, 3) skin condition, 4) positioning, 5) wheelchair incidents, 6) psychosocial issues, 7) restricted wheelchair participation, 8) limited wheelchair skills and knowledge, and 9) technical problems. In phase II, 92 individuals who received a wheelchair were eligible, 71 out of 92 accepted (77%) and 65 out of 71 (92%) completed the 3-month follow-up. In the sample of 65 participants, a wheelchair-related adverse outcome was confirmed by a rehabilitation professional for 58.5%, and at least one recommendation was given to 66.2% during the 3-month monitoring period. A majority of participants found the intervention useful (82.8%) and said they intended to use the MOvIT monitoring questionnaire in the future (81.5%). Participants made suggestions to make the calls more adaptive to various ability profiles. CONCLUSIONS: Automated calls tailored for individuals with mobility limitations and associated comorbidities are a promising approach to reach clients who need post rehabilitation support. PMID- 26376855 TI - Erratum to: Humanization of the mouse mammary gland by replacement of the luminal layer with genetically engineered preneoplastic human cells. AB - Due to a typesetting error, the labelling was changed and the figures in this article [1] were presented in the order 2, 4, 10, 6, 1, 3, 5, 7, 8, 9, 11, 12, 13, 14 and the supplementary figure links were inverted. The revised version has the figures in the correct order. PMID- 26376854 TI - Sympathetic fibre sprouting in the skin contributes to pain-related behaviour in spared nerve injury and cuff models of neuropathic pain. AB - BACKGROUND: Cuff and spared nerve injury (SNI) in the sciatic territory are widely used to model neuropathic pain. Because nociceptive information is first detected in skin, it is important to understand how alterations in peripheral innervation contribute to pain in each model. Over 16 weeks in male rats, changes in sensory and autonomic innervation of the skin were described after cuff and SNI using immunohistochemistry to label myelinated (neurofilament 200 positive NF200+) and peptidergic (calcitonin gene-related peptide positive-CGRP+) primary afferents and sympathetic fibres (dopamine beta-hydroxylase positive-DBH+) RESULTS: Cuff and SNI caused an early loss and later reinnervation of NF200 and CGRP fibres in the plantar hind paw skin. In both models, DBH+ fibres sprouted into the upper dermis of the plantar skin 4 and 6 weeks after injury. Despite these similarities, behavioural pain measures were significantly different in each model. Sympathectomy using guanethidine significantly alleviated mechanical allodynia 6 weeks after cuff, when peak sympathetic sprouting was observed, having no effect at 2 weeks, when fibres were absent. In SNI animals, mechanical allodynia in the lateral paw was significantly improved by guanethidine at 2 and 6 weeks, and the development of cold hyperalgesia, which roughly paralleled the appearance of ectopic sympathetic fibres, was alleviated by guanethidine at 6 weeks. Sympathetic fibres did not sprout into the dorsal root ganglia at 2 or 6 weeks, indicating their unimportance to pain behaviour in these two models. CONCLUSIONS: Alterations in sympathetic innervation in the skin represents an important mechanism that contributes to pain in cuff and SNI models of neuropathic pain. PMID- 26376856 TI - Effects of density dependence, zooplankton and temperature on blue whiting Micromesistius poutassou growth. AB - Blue whiting Micromesistius poutassou mean total length at age in the north-east Atlantic Ocean was found to vary by around +/-6% during the period 2004-2011 and mean mass at age by +/-22% during the years 1981-2013. Linear modelling provided strong evidence that these phenotypic growth variations can be explained by trophic conditions, mainly negative density dependence and also food availability, and a negative long-term temperature effect on asymptotic size. PMID- 26376857 TI - Mutation in the Monocarboxylate Transporter 12 Gene Affects Guanidinoacetate Excretion but Does Not Cause Glucosuria. AB - A heterozygous mutation (c.643C>A; p.Q215X) in the monocarboxylate transporter 12 encoding gene MCT12 (also known as SLC16A12) that mediates creatine transport was recently identified as the cause of a syndrome with juvenile cataracts, microcornea, and glucosuria in a single family. Whereas the MCT12 mutation cosegregated with the eye phenotype, poor correlation with the glucosuria phenotype did not support a pathogenic role of the mutation in the kidney. Here, we examined MCT12 in the kidney and found that it resides on basolateral membranes of proximal tubules. Patients with MCT12 mutation exhibited reduced plasma levels and increased fractional excretion of guanidinoacetate, but normal creatine levels, suggesting that MCT12 may function as a guanidinoacetate transporter in vivo However, functional studies in Xenopus oocytes revealed that MCT12 transports creatine but not its precursor, guanidinoacetate. Genetic analysis revealed a separate, undescribed heterozygous mutation (c.265G>A; p.A89T) in the sodium/glucose cotransporter 2-encoding gene SGLT2 (also known as SLC5A2) in the family that segregated with the renal glucosuria phenotype. When overexpressed in HEK293 cells, the mutant SGLT2 transporter did not efficiently translocate to the plasma membrane, and displayed greatly reduced transport activity. In summary, our data indicate that MCT12 functions as a basolateral exit pathway for creatine in the proximal tubule. Heterozygous mutation of MCT12 affects systemic levels and renal handling of guanidinoacetate, possibly through an indirect mechanism. Furthermore, our data reveal a digenic syndrome in the index family, with simultaneous MCT12 and SGLT2 mutation. Thus, glucosuria is not part of the MCT12 mutation syndrome. PMID- 26376861 TI - Modeling the Neurologic and Cognitive Effects of Hyponatremia. PMID- 26376859 TI - Molecular Basis of Factor H R1210C Association with Ocular and Renal Diseases. AB - The complement factor H (FH) mutation R1210C, which was described in association with atypical hemolytic uremic syndrome (aHUS), also confers high risk of age related macular degeneration (AMD) and associates with C3 glomerulopathy (C3G). To reveal the molecular basis of these associations and to provide insight into what determines the disease phenotype in FH-R1210C carriers, we identified FH R1210C carriers in our aHUS, C3G, and AMD cohorts. Disease status, determined in patients and relatives, revealed an absence of AMD phenotypes in the aHUS cohort and, vice versa, a lack of renal disease in the AMD cohort. These findings were consistent with differences in the R1210C-independent overall risk for aHUS and AMD between mutation carriers developing one pathology or the other. R1210C is an unusual mutation that generates covalent complexes between FH and HSA. Using purified FH proteins and surface plasmon resonance analyses, we demonstrated that formation of these FH-HSA complexes impairs accessibility to all FH functional domains. These data suggest that R1210C is a unique C-terminal FH mutation that behaves as a partial FH deficiency, predisposing individuals to diverse pathologies with distinct underlying pathogenic mechanisms; the final disease outcome is then determined by R1210C-independent genetic risk factors. PMID- 26376871 TI - CINcere Modelling: What Have Mouse Models for Chromosome Instability Taught Us? AB - Chromosomal instability (CIN) is a process leading to errors in chromosome segregation and results in aneuploidy, a state in which cells have an abnormal number of chromosomes. CIN is a hallmark of cancer, and furthermore linked to ageing and age-related diseases such as Alzheimer's. Various mouse models have been developed to explore the role of CIN in ageing and cancer. While these models reveal only a modest contribution of CIN to the initiation of cancer, they also clearly show that CIN is a powerful accelerator of cancer in a predisposed background. Other than cancer, CIN also appears to provoke premature ageing in some of the CIN models. In this review, we discuss the phenotypes of the various available mouse models, what we have learnt so far, and importantly, also which questions still need to be addressed. PMID- 26376870 TI - DNA Repair and Chromosomal Translocations. AB - The balance between DNA damage, especially double strand breaks, and DNA damage repair is a critical determinant of chromosomal translocation frequency. The non homologous end-joining repair (NHEJ) pathways seem to play the major role in the generation of chromosomal translocations. The "landscape" of chromosomal translocation identified in malignancies is largely due to selection processes which operate on the growth advantages conveyed to the cells by the functional consequences of chromosomal translocations (i.e., oncogenic fusion proteins and overexpression of oncogenes, both compromising tumor suppressor gene functions). Newer studies have shown that there is an abundance of local rearrangements in many tumors, like small deletions and inversions. A better understanding of the interplay between DNA repair mechanisms and the generation of tumorigenic translocations will, among many other things, depend on an improved understanding of DNA repair mechanisms and their interplay with chromatin and the 3D organization of the interphase nucleus. PMID- 26376873 TI - Genetic Instability and Disease Prognostication. AB - Genetic instability is a striking feature of human cancers, with an impact on the genesis, progression and prognosis. The clinical importance of genomic instability and aneuploidy is underscored by its association with poor patient outcome in multiple cancer types, including breast and colon cancer. Interestingly, there is growing evidence that prognostic gene expression signatures simply reflect the degree of genomic instability. Additionally, also the proteome is affected by aneuploidy and has therefore become a powerful tool to screen for new targets for therapy, diagnosis and prognostication. In this context, the chapter presents the impact of genomic instability on disease prognostication occurring in human cancers. PMID- 26376864 TI - Gene-based meta-analysis of genome-wide association studies implicates new loci involved in obesity. AB - To date, genome-wide association studies (GWASs) have identified >100 loci with single variants associated with body mass index (BMI). This approach may miss loci with high allelic heterogeneity; therefore, the aim of the present study was to use gene-based meta-analysis to identify regions with high allelic heterogeneity to discover additional obesity susceptibility loci. We included GWAS data from 123 865 individuals of European descent from 46 cohorts in Stage 1 and Metabochip data from additional 103 046 individuals from 43 cohorts in Stage 2, all within the Genetic Investigation of ANthropometric Traits (GIANT) consortium. Each cohort was tested for association between ~2.4 million (Stage 1) or ~200 000 (Stage 2) imputed or genotyped single variants and BMI, and summary statistics were subsequently meta-analyzed in 17 941 genes. We used the 'VErsatile Gene-based Association Study' (VEGAS) approach to assign variants to genes and to calculate gene-based P-values based on simulations. The VEGAS method was applied to each cohort separately before a gene-based meta-analysis was performed. In Stage 1, two known (FTO and TMEM18) and six novel (PEX2, MTFR2, SSFA2, IARS2, CEP295 and TXNDC12) loci were associated with BMI (P < 2.8 * 10(-6) for 17 941 gene tests). We confirmed all loci, and six of them were gene-wide significant in Stage 2 alone. We provide biological support for the loci by pathway, expression and methylation analyses. Our results indicate that gene based meta-analysis of GWAS provides a useful strategy to find loci of interest that were not identified in standard single-marker analyses due to high allelic heterogeneity. PMID- 26376874 TI - Causes of Chromosomal Instability. AB - The majority of human cancer cells are highly aneuploid harboring chromosome numbers deviating from the modal number of 46. In cancer, aneuploidy is a consequence of an increased rate of whole chromosome missegregation during mitosis, a process known as chromosomal instability (CIN). In fact, CIN is a hallmark of human cancer and is thought to contribute to tumorigenesis, tumor progression, and the development of therapy resistance by providing a high genetic variability that might foster rapid adaptation processes. However, the molecular mechanisms that cause chromosome missegregation in cancer cells are still poorly understood. So far, several mechanisms underlying CIN have been proposed and some of them are indeed detectable in human cancer cells exhibiting CIN. Examples include, for instance, weakened spindle checkpoint signaling, supernumerary centrosomes, defects in chromatid cohesion, abnormal kinetochore microtubule attachments and increased spindle microtubule dynamics. Here, the mechanisms leading to CIN in human cancer cells are summarized. PMID- 26376876 TI - Yeast as Models of Mitotic Fidelity. AB - Chromosome missegregation leads to aneuploidy which is defined as the cellular state of having a chromosome count that is not an exact multiple of the haploid number. Aneuploidy is associated with human diseases including mental retardation, neurodegenerative diseases and cancer. In addition, aneuploidy is the major cause of spontaneous abortions and its occurrence increases with aging. Therefore, it is important to understand the molecular mechanisms by which cells respond and adapt to aneuploidy. Saccharomyces cerevisiae has proven to be a good model to study the effects aneuploidy elicits on cellular homeostasis and physiology. This chapter focuses on the current understanding of how the yeast S. cerevisiae responds to the acquisition of extra chromosomes and highlights how studies in aneuploid yeasts provide insights onto the effects of aneuploidy in human cells. PMID- 26376860 TI - Chronic Hyponatremia Causes Neurologic and Psychologic Impairments. AB - Hyponatremia is the most common clinical electrolyte disorder. Once thought to be asymptomatic in response to adaptation by the brain, recent evidence suggests that chronic hyponatremia may be linked to attention deficits, gait disturbances, risk of falls, and cognitive impairments. Such neurologic defects are associated with a reduction in quality of life and may be a significant cause of mortality. However, because underlying diseases such as adrenal insufficiency, heart failure, liver cirrhosis, and cancer may also affect brain function, the contribution of hyponatremia alone to neurologic manifestations and the underlying mechanisms remain unclear. Using a syndrome of inappropriate secretion of antidiuretic hormone rat model, we show here that sustained reduction of serum sodium ion concentration induced gait disturbances; facilitated the extinction of a contextual fear memory; caused cognitive impairment in a novel object recognition test; and impaired long-term potentiation at hippocampal CA3-CA1 synapses. In vivo microdialysis revealed an elevated extracellular glutamate concentration in the hippocampus of chronically hyponatremic rats. A sustained low extracellular sodium ion concentration also decreased glutamate uptake by primary astrocyte cultures, suggesting an underlying mechanism of impaired long term potentiation. Furthermore, gait and memory performances of corrected hyponatremic rats were equivalent to those of control rats. Thus, these results suggest chronic hyponatremia in humans may cause gait disturbance and cognitive impairment, but these abnormalities are reversible and careful correction of this condition may improve quality of life and reduce mortality. PMID- 26376877 TI - The Diverse Effects of Complex Chromosome Rearrangements and Chromothripsis in Cancer Development. AB - In recent years, enormous progress has been made with respect to the identification of somatic mutations that contribute to cancer development. Mutation types range from small substitutions to large structural genomic rearrangements, including complex reshuffling of the genome. Sets of mutations in individual cancer genomes may show specific signatures, which can be provoked by both exogenous and endogenous forces. One of the most remarkable mutation patterns observed in human cancers involve massive rearrangement of just a few chromosomal regions. This phenomenon has been termed chromothripsis and appears widespread in a multitude of cancer types. Chromothripsis provides a way for cancer to rapidly evolve through a one-off massive change in genome structure as opposed to a gradual process of mutation and selection. This chapter focuses on the origin, prevalence and impact of chromothripsis and related complex genomic rearrangements during cancer development. PMID- 26376858 TI - CD103+ Dendritic Cells Elicit CD8+ T Cell Responses to Accelerate Kidney Injury in Adriamycin Nephropathy. AB - CD103(+) dendritic cells (DCs) in nonlymphoid organs exhibit two main functions: maintaining tolerance by induction of regulatory T cells and protecting against tissue infection through cross-presentation of foreign antigens to CD8(+) T cells. However, the role of CD103(+) DCs in kidney disease is unknown. In this study, we show that CD103(+) DCs are one of four subpopulations of renal mononuclear phagocytes in normal kidneys. CD103(+) DCs expressed DC-specific surface markers, transcription factors, and growth factor receptors and were found in the kidney cortex but not in the medulla. The number of kidney CD103(+) DCs was significantly higher in mice with adriamycin nephropathy (AN) than in normal mice, and depletion of CD103(+) DCs attenuated kidney injury in AN mice. In vitro, kidney CD103(+) DCs preferentially primed CD8(+) T cells and did not directly induce tubular epithelial cell apoptosis. Adoptive transfer of CD8(+) T cells significantly exacerbated kidney injury in AN SCID mice, whereas depletion of CD103(+) DCs in these mice impaired activation and proliferation of transfused CD8(+) T cells and prevented the exacerbation of kidney injury associated with this transfusion. In conclusion, kidney CD103(+) DCs display a pathogenic role in murine CKD via activation of CD8(+) T cells. PMID- 26376872 TI - Telomere Dysfunction, Chromosomal Instability and Cancer. AB - Telomeres form protective caps at the ends of linear chromosomes to prevent nucleolytic degradation, end-to-end fusion, irregular recombination, and chromosomal instability. Telomeres are composed of repetitive DNA sequences (TTAGGG)n in humans, that are bound by specialized telomere binding proteins. Telomeres lose capping function in response to telomere shortening, which occurs during each division of cells that lack telomerase activity-the enzyme that can synthesize telomeres de novo. Telomeres have a dual role in cancer: telomere shortening can lead to induction of chromosomal instability and to the initiation of tumors, however, initiated tumors need to reactivate telomerase in order to stabilize chromosomes and to gain immortal growth capacity. In this review, we summarize current knowledge on the role of telomeres in the maintenance of chromosomal stability and carcinogenesis. PMID- 26376878 TI - Consequences of Aneuploidy in Cancer: Transcriptome and Beyond. AB - Cancer cells differ from normal healthy cells in multiple aspects ranging from altered cellular signaling through metabolic changes to aberrant chromosome content, so called aneuploidy. The large-scale changes in copy numbers of chromosomes or large chromosomal regions due to aneuploidy alter significantly the gene expression, as several hundreds of genes are gained or lost. Comparison of quantitative genome, transcriptome and proteome data enables dissection of the molecular causes that underlie the gene expression changes observed in cancer cells and provides a new perspective on the molecular consequences of aneuploidy. Here, we will map to what degree aneuploidy affects the expression of genes located on the affected chromosomes. We will also address the effects of aneuploidy on global gene expression in cancer cells as well as whether and how it may contribute to the physiology of cancer cells. PMID- 26376865 TI - GLUT10 deficiency leads to oxidative stress and non-canonical alphavbeta3 integrin-mediated TGFbeta signalling associated with extracellular matrix disarray in arterial tortuosity syndrome skin fibroblasts. AB - Arterial tortuosity syndrome (ATS) is an autosomal recessive connective tissue disorder caused by loss-of-function mutations in SLC2A10, which encodes facilitative glucose transporter 10 (GLUT10). The role of GLUT10 in ATS pathogenesis remains an enigma, and the transported metabolite(s), i.e. glucose and/or dehydroascorbic acid, have not been clearly elucidated. To discern the molecular mechanisms underlying the ATS aetiology, we performed gene expression profiling and biochemical studies on skin fibroblasts. Transcriptome analyses revealed the dysregulation of several genes involved in TGFbeta signalling and extracellular matrix (ECM) homeostasis as well as the perturbation of specific pathways that control both the cell energy balance and the oxidative stress response. Biochemical and functional studies showed a marked increase in ROS induced lipid peroxidation sustained by altered PPARgamma function, which contributes to the redox imbalance and the compensatory antioxidant activity of ALDH1A1. ATS fibroblasts also showed activation of a non-canonical TGFbeta signalling due to TGFBRI disorganization, the upregulation of TGFBRII and connective tissue growth factor, and the activation of the alphavbeta3 integrin transduction pathway, which involves p125FAK, p60Src and p38 MAPK. Stable GLUT10 expression in patients' fibroblasts normalized redox homeostasis and PPARgamma activity, rescued canonical TGFbeta signalling and induced partial ECM re organization. These data add new insights into the ATS dysregulated biological pathways and definition of the pathomechanisms involved in this disorder. PMID- 26376868 TI - Flux measurements and maintenance energy for carbon dioxide utilization by Methanococcus maripaludis. AB - BACKGROUND: The rapidly growing mesophilic methanogen Methanococcus maripaludis S2 has a unique ability to consume both CO2 and N2, the main components of a flue gas, and produce methane with H2 as the electron donor. The existing literature lacks experimental measurements of CO2 and H2 uptake rates and CH4 production rates on M. maripaludis. Furthermore, it lacks estimates of maintenance energies for use with genome-scale models. In this paper, we performed batch culture experiments on M. maripaludis S2 using CO2 as the sole carbon substrate to quantify three key extracellular fluxes (CO2, H2, and CH4) along with specific growth rates. For precise computation of these fluxes from experimental measurements, we developed a systematic process simulation approach. Then, using an existing genome-scale model, we proposed an optimization procedure to estimate maintenance energy parameters: growth associated maintenance (GAM) and non-growth associated maintenance (NGAM). RESULTS: The measured extracellular fluxes for M. maripaludis showed excellent agreement with in silico predictions from a validated genome-scale model (iMM518) for NGAM = 7.836 mmol/gDCW/h and GAM = 27.14 mmol/gDCW. M. maripaludis achieved a CO2 to CH4 conversion yield of 70-95 % and a growth yield of 3.549 +/- 0.149 g DCW/mol CH4 during the exponential phase. The ATP gain of 0.35 molATP/molCH4 for M. maripaludis, computed using NGAM, is in the acceptable range of 0.3-0.7 mol ATP/molCH4 reported for methanogens. Interestingly, the uptake distribution of amino acids, quantified using iMM518, confirmed alanine to be the most preferred amino acids for growth and methanogenesis. CONCLUSIONS: This is the first study to report experimental gas consumption and production rates for the growth of M. maripaludis on CO2 and H2 in minimal media. A systematic process simulation and optimization procedure was successfully developed to precisely quantify extracellular fluxes along with cell growth and maintenance energy parameters. Our growth yields, ATP gain, and energy parameters fall within acceptable ranges known in the literature for hydrogenotrophic methanogens. PMID- 26376867 TI - Tumor-to-tumor metastases in Cowden's disease: an autopsy case report and review of the literature. AB - Tumor-to-tumor metastasis is a rare phenomenon, but it has been suggested to be more frequent in patients with hereditary cancer syndrome. We report an autopsy case of tumor-to-tumor metastasis in a 75-year-old male. At 6 months before his death, the patient complained of hoarseness and dysphagia, and clinical whole body examinations revealed advanced lung adenocarcinoma (T4N2M1b, Stage IV), multiple skin verrucas, gastrointestinal polyposis, goiters, and cerebellar dysplastic gangliocytoma (Lhermitte-Duclos disease), while PTEN gene mutation was detected in his serum. An mTOR inhibitor had been used to treat his lung adenocarcinoma, but he developed aspiration pneumonia and died of respiratory failure. Autopsy revealed that the lung adenocarcinoma had metastasized to cavernous hemangiomas of the right atrial appendage and liver, to cerebellar dysplastic gangliocytoma and to multiple organs such as the liver, kidney, adrenal glands and spine. This is the first reported case of Cowden's disease with multiple tumor-to-tumor metastases. PMID- 26376869 TI - EasyClone 2.0: expanded toolkit of integrative vectors for stable gene expression in industrial Saccharomyces cerevisiae strains. AB - Saccharomyces cerevisiae is one of the key cell factories for production of chemicals and active pharmaceuticals. For large-scale fermentations, particularly in biorefinery applications, it is desirable to use stress-tolerant industrial strains. However, such strains are less amenable for metabolic engineering than the standard laboratory strains. To enable easy delivery and overexpression of genes in a wide range of industrial S. cerevisiae strains, we constructed a set of integrative vectors with long homology arms and dominant selection markers. The vectors integrate into previously validated chromosomal locations via double cross-over and result in homogenous stable expression of the integrated genes, as shown for several unrelated industrial strains. Cre-mediated marker rescue is possible for removing markers positioned on different chromosomes. To demonstrate the applicability of the presented vector set for metabolic engineering of industrial yeast, we constructed xylose-utilizing strains overexpressing xylose isomerase, xylose transporter and five genes of the pentose phosphate pathway. PMID- 26376862 TI - Glucocerebrosidase 1 deficient Danio rerio mirror key pathological aspects of human Gaucher disease and provide evidence of early microglial activation preceding alpha-synuclein-independent neuronal cell death. AB - Autosomal recessively inherited glucocerebrosidase 1 (GBA1) mutations cause the lysosomal storage disorder Gaucher's disease (GD). Heterozygous GBA1 mutations (GBA1(+/-)) are the most common risk factor for Parkinson's disease (PD). Previous studies typically focused on the interaction between the reduction of glucocerebrosidase (enzymatic) activity in GBA1(+/-) carriers and alpha-synuclein mediated neurotoxicity. However, it is unclear whether other mechanisms also contribute to the increased risk of PD in GBA1(+/-) carriers. The zebrafish genome does not contain alpha-synuclein (SNCA), thus providing a unique opportunity to study pathogenic mechanisms unrelated to alpha-synuclein toxicity. Here we describe a mutant zebrafish line created by TALEN genome editing carrying a 23 bp deletion in gba1 (gba1(c.1276_1298del)), the zebrafish orthologue of human GBA1. Marked sphingolipid accumulation was already detected at 5 days post fertilization with accompanying microglial activation and early, sustained up regulation of miR-155, a master regulator of inflammation. gba1(c.1276_1298del) mutant zebrafish developed a rapidly worsening phenotype from 8 weeks onwards with striking reduction in motor activity by 12 weeks. Histopathologically, we observed marked Gaucher cell invasion of the brain and other organs. Dopaminergic neuronal cell count was normal through development but reduced by >30% at 12 weeks in the presence of ubiquitin-positive, intra-neuronal inclusions. This gba1(c.1276_1298del) zebrafish line is the first viable vertebrate model sharing key pathological features of GD in both neuronal and non-neuronal tissue. Our study also provides evidence for early microglial activation prior to alpha synuclein-independent neuronal cell death in GBA1 deficiency and suggests upregulation of miR-155 as a common denominator across different neurodegenerative disorders. PMID- 26376880 TI - Brian Ernest Kendall. PMID- 26376887 TI - Study links SSRIs to violent crime in young adults. PMID- 26376875 TI - Patterns of Chromosomal Aberrations in Solid Tumors. AB - Chromosomal abnormalities are a defining feature of solid tumors. Such cytogenetic alterations are mainly classified into structural chromosomal aberrations and copy number alterations, giving rise to aneuploid karyotypes. The increasing detection of these genetic changes allowed the description of specific tumor entities and the associated patterns of gene expression. In fact, tumor specific landscapes of gross genomic copy number changes, including aneuploidies of entire chromosome arms and chromosomes result in a global deregulation of the transcriptome of cancer cells. Furthermore, the molecular characterization of cytogenetic abnormalities has provided insights into the mechanisms of tumorigenesis and has, in a few instances, led to the clinical implementation of effective diagnostic and prognostic tools, as well as treatment strategies that target a specific genetic abnormality. PMID- 26376879 TI - Aldolase B inhibits metastasis through Ten-Eleven Translocation 1 and serves as a prognostic biomarker in hepatocellular carcinoma. AB - BACKGROUND: Downregulation of Aldolase B (ALDOB) has been reported in hepatocellular carcinoma. However, its clinical significance and its role in pathogenesis of HCC remain largely unknown. METHODS: We analyzed the expression of ALDOB and its clinical features in a large cohort of 313 HCC patients using tissue microarray and immunohistochemistry. Moreover, the function of stably overexpressed ALDOB in HCC cells was explored in vitro and in vivo. Gene expression microarray analysis was performed on ALDOB-overexpressing SMMC7721 cells to elucidate its mechanism of action. RESULTS: ALDOB downregulation in HCC was significantly correlated with aggressive characteristics including absence of encapsulation, increased tumor size (>5 cm) and early recurrence. ALDOB downregulation was indicative of a shorter recurrence-free survival (RFS) and overall survival (OS) for all HCC patients and early-stage HCC patients (BCLC 0-A and TNM I stage patients). Multiple analyses revealed that ALDOB downregulation was an independent risk factor of RFS and OS. Stable expression of ALDOB in HCC cell lines reduced cell migration in vitro and inhibited lung metastasis, intrahepatic metastasis, and reduced circulating tumor cells in vivo. Mechanistically, we found that cells stably expressing ALDOB show elevated Ten Eleven Translocation 1 (TET1) expression. Moreover, ALDOB expressing cells have higher levels of methylglyoxal than do control cells, which can upregulate TET1 expression. CONCLUSION: The downregulation of ALDOB could indicate a poor prognosis for HCC patients, and therefore, ALDOB might be considered a prognostic biomarker for HCC, especially at the early stage. In addition, ALDOB inhibits the invasive features of cell lines partly through TET1 expression. PMID- 26376890 TI - Acute lymphoblastic leukemia: an assessment of international incidence, survival, and disease burden. AB - PURPOSE: Acute lymphoblastic leukemia (ALL) is a rare hematological malignancy. With the recent introduction of a classification system for hematopoietic and lymphoid neoplasms, more comprehensive assessment of ALL epidemiology is now possible. In this study, we describe recent international incidence of ALL and project the annual number of diagnoses to 2025. We also estimate relative survival and average potential years of life lost (AYLL) to assess the societal burden of ALL. METHODS: Age-specific incidence data for ALL from select cancer registries in different geographies were obtained from the International Agency for Research on Cancer's Cancer Incidence in Five Continents Database. Country specific age-standardized rates were calculated to allow for direct comparisons between countries. ALL-specific mortality and relative survival data were only available from the United States (US) National Cancer Institute's Surveillance, Epidemiology, and End Results program; mortality rates were estimated for other countries. RESULTS: The age-standardized incidence rate of ALL during 2003-2007 ranged from 1.08 to 2.12 per 100,000 person-years in selected countries. Incidence was generally higher in the Americas and Oceania and lower in Asia and Eastern Europe. In most countries, the incidence rate of ALL in children was approximately four times that in adults. Survival was particularly poor among adults. In selected countries, the estimated AYLL ranged from 30 to 48 years for all ages and from 23 to 39 years for adults. CONCLUSIONS: Although a rare disease, ALL presents a significant public health burden given poor survival outcomes among adults, AYLL, and its importance as the most common pediatric cancer. PMID- 26376891 TI - Predictors of guideline concordance for surveillance colonoscopy recommendations in patients at a safety-net health system. AB - PURPOSE: Appropriate surveillance intervals for colorectal cancer (CRC) screening is one of the Centers for Medicare and Medicaid Services 2014 physician quality reporting system measures. Appropriateness of surveillance intervals will continue to be monitored closely, particularly as reimbursements become tied to quality measures. AIMS: Quantify and identify predictors for guideline-concordant surveillance recommendations after adenoma polypectomy. METHODS: We conducted a retrospective cohort study of patients who had colonoscopy with polypectomy at a safety-net health system between June 2011 and December 2013. Surveillance recommendations shorter and longer than guideline recommendations were defined as potential overuse and underuse. We used multivariate logistic regression to identify correlates of guideline-concordant surveillance recommendations, overuse, and underuse. RESULTS: Among 1,822 patients with polypectomy, 1,329 had >=1 adenoma. Surveillance interval recommendations were guideline-concordant in 1,410 (77.4%) patients, potential overuse in 263 (14.4%), potential underuse in 85 (4.7%), and missing in 64 (3.5%) patients. Predictors of guideline-concordant recommendations in multivariate analyses included age >65 years (OR 1.36, 95% CI 1.02-1.80), incomplete resection (OR 3.58, 95% CI 1.41-9.09), and good/excellent prep quality (OR 2.22, 95% CI 1.72-2.86). Underuse recommendations were more likely in patients with >=3 adenomas; overuse recommendations were more likely in patients with high-grade dysplasia or fair prep quality and less likely in those with piecemeal resection, >=3 adenomas, age >65, or Hispanic ethnicity. CONCLUSIONS: Surveillance recommendations are not concordant with guidelines in one of four cases. Interventions to improve prep quality and guideline concordance of surveillance recommendations can improve cost-effectiveness of CRC screening. PMID- 26376895 TI - Association between preoperative C-reactive protein level and colorectal cancer survival: a meta-analysis. AB - PURPOSE: C-reactive protein (CRP) is widely known as a major nonspecific systemic inflammatory marker. A number of previous studies have suggested that elevated preoperative CRP is associated with poor prognosis in colorectal cancer. We aimed to explore the effects of preoperative CRP on colorectal cancer survival through a meta-analysis. METHODS: A total of 21 studies, including a total of 3934 colorectal cancer patients, were eligible. The multivariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of selected studies were used to assess the summary estimates of the association between preoperative CRP and colorectal cancer survival. RESULTS: The pooled HRs of elevated preoperative CRP for earlier stage patients were 2.04 (95% CI 1.45-2.86) for OS, 4.37 (95% CI 2.63 7.27) for CSS, and 1.88 (95% CI 0.97-3.67) for DFS. The pooled HRs of a higher Glasgow Prognostic Score (GPS)/modified GPS (mGPS) for earlier stage patients were 2.20 (95% CI 1.61-3.02) for OS and 1.80 (95% CI 1.37-2.37) for CSS. The association between elevated preoperative CRP and poor survival was observed in patients with advanced cancer. Elevated CRP and GPS/mGPS were significantly associated with poor survival. CONCLUSION: Preoperative CRP and its related markers, GPS and mGPS, were significantly associated with the survival of colorectal cancer surgery patients. The HRs of GPS and mGPS were highly homogeneous across studies for all survival types. Thus, GPS and mGPS may serve as stable predictors of the survival of colorectal cancer surgery patients. PMID- 26376889 TI - Lyapunov Functions, Stationary Distributions, and Non-equilibrium Potential for Reaction Networks. AB - We consider the relationship between stationary distributions for stochastic models of reaction systems and Lyapunov functions for their deterministic counterparts. Specifically, we derive the well-known Lyapunov function of reaction network theory as a scaling limit of the non-equilibrium potential of the stationary distribution of stochastically modeled complex balanced systems. We extend this result to general birth-death models and demonstrate via example that similar scaling limits can yield Lyapunov functions even for models that are not complex or detailed balanced, and may even have multiple equilibria. PMID- 26376885 TI - Effect of gadolinium on hepatic fat quantification using multi-echo reconstruction technique with T2* correction and estimation. AB - OBJECTIVES: To determine whether hepatic fat quantification is affected by administration of gadolinium using a multiecho reconstruction technique with T2* correction and estimation. METHODS: Forty-eight patients underwent the investigational sequence for hepatic fat quantification at 3.0T MRI once before and twice after administration of gadopentetate dimeglumine (0.1 mmol/kg). A one way repeated-measures analysis of variance with pairwise comparisons was conducted to evaluate the systematic bias of fat fraction (FF) and R2* measurements between three acquisitions. Bland-Altman plots were used to assess the agreements between pre- and post-contrast FF measurements in the liver. A P value <0.05 indicated statistically significant difference. RESULTS: FF measurements of liver, spleen and spine revealed no significant systematic bias between the three measurements (P > 0.05 for all). Good agreements (95 % confidence interval) of FF measurements were demonstrated between pre-contrast and post-contrast1 (-0.49 %, 0.52 %) and post-contrast2 (-0.83 %, 0.77 %). R2* increased in liver and spleen (P = 0.039, P = 0.01) after administration of gadolinium. CONCLUSIONS: Although under the impact of an increased R2* in liver and spleen post-contrast, the investigational sequence can still obtain stable fat quantification. Therefore, it could be applied post-contrast to substantially increase the efficiency of MR examination and also provide a backup for the occasional failure of FF measurements pre-contrast. KEY POINTS: * Fat quantification with IDEAL-based investigational sequence remains stable after gadolinium administration. * It can be integrated into tri-phase liver MRI without adding scan time. * This helps optimize MR protocols and provides more useful information for clinicians. PMID- 26376882 TI - Comparison of the diagnostic performance of digital breast tomosynthesis and magnetic resonance imaging added to digital mammography in women with known breast cancers. AB - OBJECTIVES: To compare the diagnostic performance of digital breast tomosynthesis (DBT) and magnetic resonance imaging (MRI) added to mammography in women with known breast cancers. METHODS: Three radiologists independently reviewed image sets of 172 patients with 184 cancers; mammography alone, DBT plus mammography and MRI plus mammography, and scored for cancer probability using the Breast Imaging Reporting and Data System (BI-RADS). Jack-knife alternative free-response receiver-operating characteristic (JAFROC), which allows diagnostic performance estimation using single lesion as a statistical unit in a cancer-only population, was used. Sensitivity and positive predictive value (PPV) were compared using the McNemar and Fisher-exact tests. RESULTS: The JAFROC figures of merit (FOMs) was lower in DBT plus mammography (0.937) than MRI plus mammography (0.978, P = 0.0006) but higher than mammography alone (0.900, P = 0 .0013). The sensitivity was lower in DBT plus mammography (88.2 %) than MRI plus mammography (97.8 %) but higher than mammography alone (78.3 %, both P < 0 .0001). The PPV was significantly higher in DBT plus mammography (93.3 %) than MRI plus mammography (89.6 %, P = 0 .0282). CONCLUSIONS: DBT provided lower diagnostic performance than MRI as an adjunctive imaging to mammography. However, DBT had higher diagnostic performance than mammography and higher PPV than MRI. KEY POINTS: * Digital breast tomosynthesis (DBT) plus mammography was compared with MRI plus mammography. * DBT had lower sensitivity and higher PPV than MRI. * DBT had higher diagnostic performance than mammography. PMID- 26376866 TI - Abnormalities of motor function, transcription and cerebellar structure in mouse models of THAP1 dystonia. AB - DYT6 dystonia is caused by mutations in THAP1 [Thanatos-associated (THAP) domain containing apoptosis-associated protein] and is autosomal dominant and partially penetrant. Like other genetic primary dystonias, DYT6 patients have no characteristic neuropathology, and mechanisms by which mutations in THAP1 cause dystonia are unknown. Thap1 is a zinc-finger transcription factor, and most pathogenic THAP1 mutations are missense and are located in the DNA-binding domain. There are also nonsense mutations, which act as the equivalent of a null allele because they result in the generation of small mRNA species that are likely rapidly degraded via nonsense-mediated decay. The function of Thap1 in neurons is unknown, but there is a unique, neuronal 50-kDa Thap1 species, and Thap1 levels are auto-regulated on the mRNA level. Herein, we present the first characterization of two mouse models of DYT6, including a pathogenic knockin mutation, C54Y and a null mutation. Alterations in motor behaviors, transcription and brain structure are demonstrated. The projection neurons of the deep cerebellar nuclei are especially altered. Abnormalities vary according to genotype, sex, age and/or brain region, but importantly, overlap with those of other dystonia mouse models. These data highlight the similarities and differences in age- and cell-specific effects of a Thap1 mutation, indicating that the pathophysiology of THAP1 mutations should be assayed at multiple ages and neuronal types and support the notion of final common pathways in the pathophysiology of dystonia arising from disparate mutations. PMID- 26376899 TI - Do your patients with bipolar disorder use dietary supplements? PMID- 26376888 TI - Transcriptomic Heterogeneity in Cancer as a Consequence of Dysregulation of the Gene-Gene Interaction Network. AB - Many pathways are dysregulated in cancer. Dysregulation of the regulatory network results in less control of transcript levels in the cell. Hence, dysregulation is reflected in the heterogeneity of the transcriptome: the more dysregulated the pathway, the more the transcriptomic heterogeneity. We identify four scenarios for a transcriptomic heterogeneity increase (i.e., pathway dysregulation) in cancer: (1) activation of a molecular switch, (2) a structural change in a regulator, (3) a temporal change in a regulator, and (4) weakening of gene-gene interactions. These mechanisms are statistically motivated, explored in silico, and their plausibility to occur in vivo illustrated by means of oncogenomics data of breast cancer studies. PMID- 26376893 TI - PTEN expression in benign human endometrial tissue and cancer in relation to endometrial cancer risk factors. AB - PURPOSE: Clonal loss of PTEN expression occurs frequently in endometrial carcinoma and endometrial hyperplasia. Limited data from immunohistochemical studies suggest that PTEN-null appearing endometrial glands are detectable in women without pathologic abnormalities, but the relationship of PTEN expression to endometrial cancer risk factors has not been extensively explored. We evaluated relationships between endometrial cancer risk factors and loss of PTEN expression in a set of benign endometrial samples prospectively collected from women undergoing hysterectomy and in endometrial cancer tissues from a population based case-control study. METHODS: We used a validated PTEN immunohistochemical assay to assess expression in epidemiological studies designed to assess benign endometrium [Benign Reproductive Tissue Evaluation Study (n = 73); Einstein Endometrium Study (n = 19)], and endometrial cancer [Polish Endometrial Cancer Study (n = 148)] tissues. Associations between endometrial cancer risk factors (collected via study-specific risk factor questionnaires) and PTEN expression in endometrial tissues were determined using Fisher's exact tests. RESULTS: PTEN loss was detected in 19% of benign endometrial tissues versus 55% in endometrial cancers. NSAID use was statistically significantly associated with PTEN loss in the benign endometrium (p = 0.02). CONCLUSION: Our data demonstrate that PTEN loss is detectable in endometrial tissues that are benign and malignant, with substantially more frequent loss in endometrial cancer compared with benign endometrium. However, alterations in expression were unrelated to most risk factors in this analysis, except for the association with NSAID use, which may represent a chance finding or reverse causality among patients with endometriosis who may have PTEN pathway abnormalities in eutopic endometrium. Further evaluation of factors associated with PTEN loss and long-term follow-up of women with PTEN-null endometrial glands may be useful in understanding early events in endometrial carcinogenesis. PMID- 26376884 TI - Comparison of radiographic joint space width and magnetic resonance imaging for prediction of knee replacement: A longitudinal case-control study from the Osteoarthritis Initiative. AB - OBJECTIVE: To evaluate whether change in fixed-location measures of radiographic joint space width (JSW) and cartilage thickness by MRI predict knee replacement. METHODS: Knees replaced between 36 and 60 months' follow-up in the Osteoarthritis Initiative were each matched with one control by age, sex and radiographic status. Radiographic JSW was determined from fixed flexion radiographs and subregional femorotibial cartilage thickness from 3 T MRI. Changes between the annual visit before replacement (T0) and 2 years before T0 (T-2) were compared using conditional logistic regression. RESULTS: One hundred and nineteen knees from 102 participants (55.5 % women; age 64.2 +/- 8.7 [mean +/- SD] years) were studied. Fixed-location JSW change at 22.5 % from medial to lateral differed more between replaced and control knees (case-control [cc] OR = 1.57; 95 % CI: 1.23 2.01) than minimum medial JSW change (ccOR = 1.38; 95 % CI: 1.11-1.71). Medial femorotibial cartilage loss displayed discrimination similar to minimum JSW, and central tibial cartilage loss similar to fixed-location JSW. Location-independent thinning and thickening scores were elevated prior to knee replacement. CONCLUSIONS: Discrimination of structural progression between knee pre-placement cases versus controls was stronger for fixed-location than minimum radiographic JSW. MRI displayed similar discrimination to radiography and suggested greater simultaneous cartilage thickening and loss prior to knee replacement. KEY POINTS: * Fixed-location JSW predicts surgical knee replacement more strongly than minimum JSW. * MRI predicts knee replacement with similar accuracy to radiographic JSW. * MRI reveals greater cartilage thinning and thickening prior to knee replacement. PMID- 26376886 TI - Early prediction of response to neoadjuvant chemotherapy in breast cancer patients: comparison of single-voxel (1)H-magnetic resonance spectroscopy and (18)F-fluorodeoxyglucose positron emission tomography. AB - OBJECTIVES: To prospectively compare performances of single-voxel proton magnetic resonance spectroscopy ((1)H-MRS) and (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) in predicting pathologic response to neoadjuvant chemotherapy (NAC) in breast cancer patients. METHODS: Thirty-five breast cancer patients who received NAC and subsequent surgery were prospectively enrolled. MRS and FDG-PET were performed before and after the 1st NAC cycle. Percentage changes of total choline-containing compounds (tCho) via MRS, and maximum and peak standardized uptake values (SUVmax, SUVpeak) and total lesion glycolysis (TLG) via FDG-PET were measured, and their performances in predicting pathologic complete response (pCR) were compared. RESULTS: Of the 35 patients, 6 showed pCR and 29 showed non-pCR. Mean % reductions of tCho, SUVmax, SUVpeak, and TLG of the pCR group were larger than those of the non-pCR group (-80.3 +/- 13.9 % vs. -32.1 +/- 49.4 %, P = 0.025; -54.7 +/- 22.1 % vs. -26.3 +/- 33.7 %, P = 0.058; -60.7 +/ 18.3 % vs. -32.3 +/- 23.3 %, P = 0.009; -89.5 +/- 8.5 % vs. -52.6 +/- 36.2 %, P = 0.020). Diagnostic accuracy (area under ROC curve; Az, 0.911) of the % reduction of tCho was comparable to those of %SUVmax (0.822), SUVpeak (0.862), and TLG (0.879) in distinguishing pCR from non-pCR (all P > 0.05). CONCLUSION: MRS showed comparable performance to FDG-PET in early prediction of pCR in breast cancer patients. KEY POINTS: * MRS can predict response to NAC in breast cancer post-1 (st) cycle. * Changes in tCho and SUV after NAC reflect tumour cellularity changes. * MRS can be an alternative to FDG-PET in predicting response to NAC. PMID- 26376863 TI - Conditional depletion of intellectual disability and Parkinsonism candidate gene ATP6AP2 in fly and mouse induces cognitive impairment and neurodegeneration. AB - ATP6AP2, an essential accessory component of the vacuolar H+ ATPase (V-ATPase), has been associated with intellectual disability (ID) and Parkinsonism. ATP6AP2 has been implicated in several signalling pathways; however, little is known regarding its role in the nervous system. To decipher its function in behaviour and cognition, we generated and characterized conditional knockdowns of ATP6AP2 in the nervous system of Drosophila and mouse models. In Drosophila, ATP6AP2 knockdown induced defective phototaxis and vacuolated photoreceptor neurons and pigment cells when depleted in eyes and altered short- and long-term memory when depleted in the mushroom body. In mouse, conditional Atp6ap2 deletion in glutamatergic neurons (Atp6ap2(Camk2aCre/0) mice) caused increased spontaneous locomotor activity and altered fear memory. Both Drosophila ATP6AP2 knockdown and Atp6ap2(Camk2aCre/0) mice presented with presynaptic transmission defects, and with an abnormal number and morphology of synapses. In addition, Atp6ap2(Camk2aCre/0) mice showed autophagy defects that led to axonal and neuronal degeneration in the cortex and hippocampus. Surprisingly, axon myelination was affected in our mutant mice, and axonal transport alterations were observed in Drosophila. In accordance with the identified phenotypes across species, genome-wide transcriptome profiling of Atp6ap2(Camk2aCre/0) mouse hippocampi revealed dysregulation of genes involved in myelination, action potential, membrane-bound vesicles and motor behaviour. In summary, ATP6AP2 disruption in mouse and fly leads to cognitive impairment and neurodegeneration, mimicking aspects of the neuropathology associated with ATP6AP2 mutations in humans. Our results identify ATP6AP2 as an essential gene for the nervous system. PMID- 26376883 TI - An assessment on the incremental value of high-resolution magnetic resonance imaging to identify culprit plaques in atherosclerotic disease of the middle cerebral artery. AB - OBJECTIVE: Although certain morphological features depicted by high resolution, multi-contrast magnetic resonance imaging (hrMRI) have been shown to be different between culprit and non-culprit middle cerebral artery (MCA) atherosclerotic lesions, the incremental value of hrMRI to define culprit lesions over stenosis has not been assessed. METHODS: Patients suspected with MCA stenosis underwent hrMRI. Lumen and outer wall were segmented to calculate stenosis, plaque burden (PB), volume (PV), length (PL) and minimum luminal area (MLA). RESULTS: Data from 165 lesions (112 culprit and 53 non-culprit) in 139 individuals were included. Culprit lesions were larger and longer with a narrower lumen and increased PB compared with non-culprit lesions. More culprit lesions showed contrast enhancement. Both PB and MLA were better indicators than stenosis in differentiating lesion types (AUC were 0.649, 0.732 and 0.737 for stenosis, PB and MLA, respectively). Combinations of PB, MLA and stenosis could improve positive predictive value (PPV) and specificity significantly. An optimal combination of stenosis >= 50 %, PB >= 77 % and MLA <= 2.0 mm(2) produced a PPV = 85.7 %, negative predictive value = 54.1 %, sensitivity = 69.6 %, specificity = 75.5 %, and accuracy = 71.5 %. CONCLUSIONS: hrMRI plaque imaging provides incremental information to luminal stenosis in identifying culprit lesions. KEY POINTS: * High resolution MRI provides incremental information in defining culprit MCA atherosclerotic lesions. * Both plaque burden and minimum luminal area are better indicators than stenosis. * An optimal combination includes stenosis >= 50 %, PB >= 77 % and MLA <= 2.0 mm (2) . PMID- 26376894 TI - Associations between sociodemographic and clinicopathological factors and breast cancer subtypes in a population-based study. AB - PURPOSE: This study examines the factors distinguishing breast cancer (BC) subtypes. METHODS: We examined subtypes in 629 women with invasive BC, diagnosed from 2006 to 2012, and enrolled in an epidemiological study in New Jersey. Using molecular characteristics from pathology reports, BCs were categorized as luminal A, luminal B, non-luminal HER2-expressing, or triple-negative breast cancer (TNBC) subtypes. Multinomial logistic models (luminal A as referent) were used to describe BC subtype associations. RESULTS: Women with luminal B tumors were more likely to be younger at diagnosis [odds ratio (OR) 1.8, 95% confidence interval (CI) 1.0-3.4] and to have higher-grade (OR 2.6, 95% CI 1.5-4.7), larger (OR 1.9, 95% CI 1.0-3.6), and Ki67-positive tumors (OR 2.1, 95% CI 1.1-4.0). Women with non-luminal HER2-expressing BCs were more likely to have higher-grade tumors (OR 14.5, 95% CI 5.3-39.7). Women with TNBCs were more likely to be African-American (OR 1.9, 95% CI 1.0-3.4) and to have higher-grade (OR 9.7, 95% CI 5.1-18.4), larger (OR 2.2, 95% CI 1.0-4.8), and Ki67-positive (OR 2.9, 95% CI 1.6-5.2) tumors. Notably, compared to the luminal A subtype, luminal B, non-luminal HER2 expressing, and triple-negative subtypes were more frequently self-detected; however, these associations were attenuated in multivariable models. CONCLUSIONS: These findings suggest that some BC subtypes were associated with features denoting more aggressive phenotypes, namely higher grade, larger size, and Ki67 positivity, and possibly patient self-detection among some women. These findings highlight a need for enhanced screening, particularly among younger women, racial/ethnic minorities, and lower socioeconomic subgroups. PMID- 26376898 TI - Immunological function of Blimp-1 in dendritic cells and relevance to autoimmune diseases. AB - Previous studies have identified the immunological functions of transcription factor B lymphocyte-induced maturation protein-1 (Blimp-1) in various adaptive immune cell types such as T and B lymphocytes. More recently, it has been shown that Blimp-1 extends its functional roles to dendritic cells (DCs) and macrophages, two cell types belonging to the innate immune system. The protein acts as a direct and indirect regulator of target genes by recruiting chromatin modification factors and by regulating microRNA expression, respectively. In DCs, Blimp-1 has been identified as one of the components involved in antigen presentation. Genome-wide association studies identified polymorphisms associated with multiple autoimmune diseases such as system lupus erythematosus, rheumatoid arthritis, and inflammatory bowel disease in PRDM1, the gene encoding Blimp-1 protein. In this review, we will discuss the immune regulatory functions of Blimp 1 in DCs with a main focus on the tolerogenic mechanisms of Blimp-1 required to protect against the development of autoimmune diseases. PMID- 26376897 TI - Molecular studies of lupus nephritis kidneys. AB - Lupus nephritis is a devastating complication of systemic lupus erythematosus (SLE) for which current therapies are insufficiently effective. Histologic evaluation of renal biopsies is a poor predictor of therapeutic response or outcome. Integrated immunologic, genomic and proteomic approaches may yield new insights into disease pathogenesis and thereby improve therapeutic strategies for lupus nephritis. Given the lack of sequential biopsies from humans, it also remains essential to study informative animal models of disease. Cross-species analyses can identify cells or pathways that are relevant to human disease and can be further studied in mouse models. Using a systems biology approach in which we compare molecular data from kidneys of three different mouse models of lupus nephritis with data from human lupus biopsies, we have found that inflammatory events escalate rapidly around the time of proteinuria onset. This is followed by hypoxia and metabolic stress, and by tubular and endothelial dysfunction. The failure of complete reversal of these abnormalities may increase the sensitivity of the kidney to further insult. We further found that renal macrophages and dendritic cells are key players in lupus nephritis both in mouse models and humans and that macrophages display a hybrid molecular profile that reflects incomplete resolution of inflammation and excessive tissue remodeling. Finally, our studies have suggested several new biomarkers for disease stage that can now be tested longitudinally in human SLE patients. PMID- 26376892 TI - Tobacco use among low-income housing residents: does hardship motivate quit attempts? AB - PURPOSE: The purpose of this study was to examine material hardship among smokers to determine whether such hardship was positively associated with current attempts to quit tobacco use. METHODS: We analyzed cross-sectional data from the Health in Common (HIC) study, an observational study to investigate social and physical determinants of cancer risk-related behaviors among residents of low income housing in three cities in the Boston metropolitan area. In this study, three indicators of hardship were used: food hardship, financial hardship, and material hardship (food and financial hardship combined). Logistic regression models were used to obtain the odds of currently trying to quit among current smokers in the HIC (n = 170) across hardship types experienced, adjusting for sociodemographic and psychosocial factors. RESULTS: Fully adjusted models revealed no statistically significant association between trying to quit tobacco use and indicators of material hardship: food hardship and financial hardship present (OR 1.33 (0.42-4.2); food hardship and no financial hardship OR 3.83 (0.97-15.13); and financial hardship but no food hardship OR 0.5 (0.1-2.39). CONCLUSIONS: These findings suggest that even in the presence of material hardship, low-income housing resident tobacco users are not more likely to quit tobacco use; therefore, cessation efforts focused on the financial benefits of quitting may be insufficient to motivate quit attempts among low-income smokers. PMID- 26376903 TI - In South Asian people with cardiac disease, strong patient-professional relationships may increase treatment compliance. PMID- 26376900 TI - Joint modeling of repeated multivariate cognitive measures and competing risks of dementia and death: a latent process and latent class approach. AB - Joint models initially dedicated to a single longitudinal marker and a single time-to-event need to be extended to account for the rich longitudinal data of cohort studies. Multiple causes of clinical progression are indeed usually observed, and multiple longitudinal markers are collected when the true latent trait of interest is hard to capture (e.g., quality of life, functional dependency, and cognitive level). These multivariate and longitudinal data also usually have nonstandard distributions (discrete, asymmetric, bounded, etc.). We propose a joint model based on a latent process and latent classes to analyze simultaneously such multiple longitudinal markers of different natures, and multiple causes of progression. A latent process model describes the latent trait of interest and links it to the observed longitudinal outcomes using flexible measurement models adapted to different types of data, and a latent class structure links the longitudinal and cause-specific survival models. The joint model is estimated in the maximum likelihood framework. A score test is developed to evaluate the assumption of conditional independence of the longitudinal markers and each cause of progression given the latent classes. In addition, individual dynamic cumulative incidences of each cause of progression based on the repeated marker data are derived. The methodology is validated in a simulation study and applied on real data about cognitive aging obtained from a large population-based study. The aim is to predict the risk of dementia by accounting for the competing death according to the profiles of semantic memory measured by two asymmetric psychometric tests. PMID- 26376902 TI - Community palliative care use by dementia sufferers may reduce emergency department use at end of life. PMID- 26376901 TI - Multiple independent origins of auto-pollination in tropical orchids (Bulbophyllum) in light of the hypothesis of selfing as an evolutionary dead end. AB - BACKGROUND: The transition from outcrossing to selfing has long been portrayed as an 'evolutionary dead end' because, first, reversals are unlikely and, second, selfing lineages suffer from higher rates of extinction owing to a reduced potential for adaptation and the accumulation of deleterious mutations. We tested these two predictions in a clade of Madagascan Bulbophyllum orchids (30 spp.), including eight species where auto-pollinating morphs (i.e., selfers, without a 'rostellum') co-exist with their pollinator-dependent conspecifics (i.e., outcrossers, possessing a rostellum). Specifically, we addressed this issue on the basis of a time-calibrated phylogeny by means of ancestral character reconstructions and within the state-dependent evolution framework of BiSSE (Binary State Speciation and Extinction), which allowed jointly estimating rates of transition, speciation, and extinction between outcrossing and selfing. RESULTS: The eight species capable of selfing occurred in scattered positions across the phylogeny, with two likely originating in the Pliocene (ca. 4.4-3.1 Ma), one in the Early Pleistocene (ca. 2.4 Ma), and five since the mid Pleistocene (ca. <= 1.3 Ma). We infer that this scattered phylogenetic distribution of selfing is best described by models including up to eight independent outcrossing-to-selfing transitions and very low rates of speciation (and either moderate or zero rates of extinction) associated with selfing. CONCLUSIONS: The frequent and irreversible outcrossing-to-selfing transitions in Madagascan Bulbophyllum are clearly congruent with the first prediction of the dead end hypothesis. The inability of our study to conclusively reject or support the likewise predicted higher extinction rate in selfing lineages might be explained by a combination of methodological limitations (low statistical power of our BiSSE approach to reliably estimate extinction in small-sized trees) and evolutionary processes (insufficient time elapsed for selfers to go extinct). We suggest that, in these tropical orchids, a simple genetic basis of selfing (via loss of the 'rostellum') is needed to explain the strikingly recurrent transitions to selfing, perhaps reflecting rapid response to parallel and novel selective environments over Late Quaternary (<= 1.3 Ma) time scales. PMID- 26376905 TI - Daily e-cigarette use increases quit attempts and reduces smoking with no effect on cessation. PMID- 26376906 TI - Nurse-led home exercise programme improves physical function for people receiving haemodialysis. PMID- 26376907 TI - Nursing students lack confidence in dealing with domestic abuse. PMID- 26376904 TI - After the Liverpool Care Pathway clear guidance and support on end-of-life care is needed. PMID- 26376896 TI - The erythroblastic island as an emerging paradigm in the anemia of inflammation. AB - Terminal erythroid differentiation occurs in the bone marrow, within specialized niches termed erythroblastic islands. These functional units consist of a macrophage surrounded by differentiating erythroblasts and have been described more than five decades ago, but their function in the pathophysiology of erythropoiesis has remained unclear until recently. Here we propose that the central macrophage in the erythroblastic island contributes to the pathophysiology of anemia of inflammation. After introducing erythropoiesis and the interactions between the erythroblasts and the central macrophage within the erythroblastic islands, we will discuss the immunophenotypic characterization of this specific subpopulation of macrophages. We will then integrate these concepts into the currently known pathophysiological drivers of anemia of inflammation and address the role of the central macrophage in this disorder. Finally, as a means of furthering our understanding of the various concepts, we will discuss the differences between murine and rat models with regard to developmental and stress erythropoiesis in an attempt to define a model system representative of human pathophysiology. PMID- 26376911 TI - A-Project : a Training Program from ASID. PMID- 26376910 TI - Standardized Prunella vulgaris var. lilacina Extract Enhances Cognitive Performance in Normal Naive Mice. AB - Adult hippocampal neurogenesis is closely associated with neuronal plasticity, cognitive function and the etiology of neurological diseases. We previously reported that the standardized ethanolic extract of Prunella vulgaris var. lilacina (EEPV) can be used for the prevention and treatment of cognitive impairments associated with Alzheimer's disease or schizophrenia. In the present study, we investigated the effects of EEPV on cognitive ability in normal naive mice and the underlying mechanism(s) governing these effects, including adult hippocampal neurogenesis. In the passive avoidance task, sub-chronic administration of EEPV (25 or 50 mg/kg, p.o.) for 14 days markedly induced the improvement of cognitive function in mice. In addition, sub-chronic administration of EEPV (25 or 50 mg/kg) for 14 days significantly increased neural cell proliferation and the number of immature neurons, but not newly generated cell survival, in the hippocampal dentate gyrus. Increased ERK, Akt and GSK-3beta phosphorylation levels in the hippocampus were also observed after such administration. Our results indicate that EEPV may enhance cognitive function via the activation of various intracellular signaling molecules and the up-regulation of adult hippocampal neurogenesis. PMID- 26376915 TI - Saccharothrix ecbatanensis sp. nov., an actinobacterium isolated from soil. AB - A novel actinomycete, designated HM 537T, was isolated from soil in Hamedan Province, Iran. Cell-wall hydrolysates of strain HM 537T contained meso diaminopimelic acid, and whole-cell hydrolysates contained ribose, glucose, galactose, rhamnose and traces of mannose. The main phospholipids were diphosphatidylglycerol, phosphatidylethanolamine, hydroxyphosphatidylethanolamine, phosphatidylinositol and an unknown phospholipid. MK-9(H4), an unknown MK and MK-10(H4) were the predominant menaquinones. The major fatty acids included iso-C16 : 0, iso-C15 : 0, iso-C16 : 1 G and 9(?)-methyl C16 : 0. Strain HM 537T had the highest 16S rRNA gene sequence similarity to Saccharothrix hoggarensis DSM 45457T (99.5 %) and Saccharothrix saharensis DSM 45456T (99.0 %). DNA-DNA hybridization studies showed relatedness values of 13.8 +/- 3.3 % with S. hoggarensis DSM 45457T and 16.3 +/- 3.5 % with S. saharensis DSM 45456T. Based on the results of phenotypic and genotypic studies, strain HM 537T represents a novel species of the genus Saccharothrix, for which the name Saccharothrix ecbatanensis sp. nov. is proposed. The type strain is HM 537T ( = DSM 45486T = UTMC 00537T = CCUG 63021T). PMID- 26376913 TI - Characterizing and optimizing magnetosome production of Magnetospirillum sp. XM-1 isolated from Xi'an City Moat, China. AB - Pure culture of magnetotactic bacteria is desirable to understand their physiology, evolution and biomineralization. Here, we report a new strain Magnetospirillum sp. XM-1 that was recently isolated and cultivated from the eutrophic city moat of Xi'an, China. Magnetosome biomineralization, crystallographic and magnetic properties of XM-1 were characterized by using a combination of transmission electron microscopy and rock magnetic methods. Cell growth and magnetite production was optimized by response surface methodology. We found that the Magnetospirillum strain XM-1 is different from the model strain Magnetospirillum magneticum AMB-1 in terms of magnetite magnetosomes, optimal growth temperature and nutrient requirements. Sodium succinate, sodium nitrate and ferric citrate are the three most significant factors associated with the optimization of cell growth and magnetosome production for XM-1. PMID- 26376912 TI - Metalliferous Biosignatures for Deep Subsurface Microbial Activity. AB - The interaction of microbes and metals is widely assumed to have occurred in surface or very shallow subsurface environments. However new evidence suggests that much microbial activity occurs in the deep subsurface. Fluvial, lacustrine and aeolian 'red beds' contain widespread centimetre-scale reduction spheroids in which a pale reduced spheroid in otherwise red rocks contains a metalliferous core. Most of the reduction of Fe (III) in sediments is caused by Fe (III) reducing bacteria. They have the potential to reduce a range of metals and metalloids, including V, Cu, Mo, U and Se, by substituting them for Fe (III) as electron acceptors, which are all elements common in reduction spheroids. The spheroidal morphology indicates that they were formed at depth, after compaction, which is consistent with a microbial formation. Given that the consequences of Fe (III) reduction have a visual expression, they are potential biosignatures during exploration of the terrestrial and extraterrestrial geological record. There is debate about the energy available from Fe (III) reduction on Mars, but the abundance of iron in Martian soils makes it one of the most valuable prospects for life there. Entrapment of the microbes themselves as fossils is possible, but a more realistic target during the exploration of Mars would be the colour contrasts reflecting selective reduction or oxidation. This can be achieved by analysing quartz grains across a reduction spheroid using Raman spectroscopy, which demonstrates its suitability for life detection in subsurface environments. Microbial action is the most suitable explanation for the formation of reduction spheroids and may act as metalliferous biosignatures for deep subsurface microbial activity. PMID- 26376914 TI - Altered intestinal functions and increased local inflammation in insulin resistant obese subjects: a gene-expression profile analysis. AB - BACKGROUND: Metabolic alterations relevant to postprandial dyslipidemia were previously identified in the intestine of obese insulin-resistant subjects. The aim of the study was to identify the genes deregulated by systemic insulin resistance in the intestine of severely obese subjects. METHODS: Transcripts from duodenal samples of insulin-sensitive (HOMA-IR < 3, n = 9) and insulin-resistant (HOMA-IR > 7, n = 9) obese subjects were assayed by microarray (Illumina HumanHT 12). RESULTS: A total of 195 annotated genes were identified as differentially expressed between these two groups (Fold change > 1.2). Of these genes, 36 were found to be directly involved in known intestinal functions, including digestion, extracellular matrix, endocrine system, immunity and cholesterol metabolism. Interestingly, all differentially expressed genes (n = 8) implicated in inflammation and oxidative stress were found to be upregulated in the intestine of insulin-resistant compared to insulin-sensitive subjects. Metabolic pathway analysis revealed that several signaling pathways involved in immunity and inflammation were significantly enriched in differently expressed genes and were predicted to be activated in the intestine of insulin-resistant subjects. Using stringent criteria (Fold change > 1.5; FDR < 0.05), three genes were found to be significantly and differently expressed in the intestine of insulin-resistant compared to insulin-sensitive subjects: the transcripts of the insulinotropic glucose-dependant peptide (GIP) and of the beta-microseminoprotein (MSMB) were significantly reduced, but that of the humanin like-1 (MTRNR2L1) was significantly increased. CONCLUSION: These results underline that systemic insulin resistance is associated with remodeling of key intestinal functions. Moreover, these data indicate that small intestine metabolic dysfunction is accompanied with a local amplification of low-grade inflammatory process implicating several pathways. Genes identified in this study are potentially triggered throughout the development of intestinal metabolic abnormalities, which could contribute to dyslipidemia, a component of metabolic syndrome and diabetes. PMID- 26376916 TI - The Diagnostic Accuracy of Prolonged Ambulatory Versus Routine EEG. AB - Prolonged ambulatory electroencephalography (paEEG) is increasingly used in clinical practice but its diagnostic accuracy relative to that of routine EEG (rEEG) remains uncertain. We examined a consecutive sample of 72 individuals who had undergone 32-channel paEEG immediately after an rEEG, creating perfectly matched EEG samples. Each recording was prospectively assessed for epileptiform discharges (ED) and nonepileptiform abnormalities. The median paEEG duration was 22.5 hours (interquartile range: 22.0-23.0). The sensitivity of paEEG was 2.23 times greater than that of rEEG [sensitivity ratio: 2.23 (95% CI=1.49-3.34)] if a positive test was limited to the presence of epileptiform discharges. This benefit of paEEG versus rEEG was no longer evident if the definition of a positive test included nonepileptiform abnormalities (sensitivity ratio 1.26; 95% CI=1.02-1.55). The specificity of the 2 tests was not evidently different (specificity ratio 0.67; 95% CI=0.17-2.67). Twenty-six percent of paEEG recorded epileptic seizures while none of the rEEG did (absolute difference 26.0% (95% CI=11.8-40.2). Our findings quantify the benefit of 32-channel paEEG, relative to rEEG, and support its role in the diagnosis and characterization of epilepsy. PMID- 26376909 TI - Psychosocial work factors and sleep problems: findings from the French national SIP survey. AB - OBJECTIVES: This study aimed at exploring the cross-sectional and prospective associations between psychosocial work factors and sleep problems. METHODS: The study population consisted of a national representative sample of the French working population (SIP survey). The sample sizes were 7506 and 3555 for the cross-sectional and prospective analyses. Sleep problems were defined by either sleep disturbances or insufficient sleep duration at least several times a week. Psychosocial work factors included classical (job strain model factors) and emergent factors (recognition, insecurity, role/ethical conflict, emotional demands, work-life imbalance, etc.). Occupational factors related to working time/hours and physical work environment were also included as well as covariates related to factors outside work. Statistical analyses were performed using weighted Poisson regression analysis. RESULTS: In the cross-sectional analyses, psychological demands, low social support, low recognition, emotional demands, perception of danger, work-life imbalance and night work were found to be associated with sleep problems. In the prospective analyses, psychological demands and night work were predictive of sleep problems. Using a less conservative method, more factors were found to be associated with sleep problems. Dose-response associations were observed, showing that the more frequent the exposure to these factors, the higher the risk of sleep problems. No effect of repeated exposure was found on sleep problems. CONCLUSION: Classical and emergent psychosocial work factors were associated with sleep problems. More prospective studies and prevention policies may be needed. PMID- 26376922 TI - Fabrication and characterization of plasmonic nanocone antennas for strong spontaneous emission enhancement. AB - Plasmonic antennas are attractive nanostructures for a large variety of studies ranging from fundamental aspects of light-matter interactions at the nanoscale to industry-relevant applications such as ultrasensitive sensing, enhanced absorption in solar cells or solar fuel generation. A particularly interesting feature of these antennas is that they can enhance the fluorescence properties of emitters. Theoretical calculations have shown that nanocone antennas provide ideal results, but a high degree of manufacturing precision and control is needed to reach optimal performance. In this study, we report on the fabrication of nanocones with base diameters and heights in the range of 100 nm with variable aspect ratios using focused ion beam milling of sputtered nano-crystalline gold layers. The controlled fabrication process allows us to obtain cones with tailored plasmon resonances. The measured plasmon spectra show very good agreement with finite-difference time-domain calculations. Theoretical investigations predict that these nanocones can enhance the spontaneous emission rate of a quantum emitter by several hundred times while keeping its quantum efficiency above 60%. PMID- 26376924 TI - Rhodium(II)-Catalyzed Cycloaddition Reactions of Non-classical 1,5-Dipoles for the Formation of Eight-Membered Heterocycles. AB - A new type of intermolecular rhodium(II)-catalyzed [5+3] cycloaddition has been developed. This higher-order cycloaddition between pyridinium zwitterion 1,5 dipole equivalents and enol diazoacetates enables the formation of eight-membered heterocyclic skeletons, which are otherwise difficult to construct. The optimized cycloaddition occurs efficiently under mild conditions with a wide range of pyridinium zwitterions and with high functional-group tolerance. PMID- 26376919 TI - Successful resolution of symmetrical peripheral gangrene after severe acute pancreatitis: a case report. AB - INTRODUCTION: Symmetrical peripheral gangrene is an uncommon but devastating complication in critically ill patients, and it has a high mortality. It is seen in a wide variety of medical conditions, presenting as symmetrical gangrene of two or more extremities without large blood vessel obstruction. CASE PRESENTATION: We report a case of a 44-year-old Chinese man who was diagnosed with alcohol-related severe acute pancreatitis and presented with systemic inflammatory response syndrome and intractable vomiting. On the fourth day of admission, the patient developed cyanosis and gangrene of the fingers bilaterally. His cyanosis and gangrene did not resolve despite tapering of the vasopressor treatment. Gradually, his digital gangrene improved after administration of anti-platelet medication and pentoxifylline. CONCLUSIONS: To the best of our knowledge, this is the first case report of symmetrical peripheral gangrene occurring after acute pancreatitis with successful resolution. We highlight the importance of prompt and aggressive fluid resuscitation and consideration of multiple treatment options to prevent a hypovolemic state caused by acute pancreatitis. PMID- 26376923 TI - Indentation Measurements to Validate Dynamic Elasticity Imaging Methods. AB - We describe macro-indentation techniques for estimating the elastic modulus of soft hydrogels. Our study describes (a) conditions under which quasi-static indentation can validate dynamic shear-wave imaging estimates and (b) how each of these techniques uniquely biases modulus estimates as they couple to the sample geometry. Harmonic shear waves between 25 and 400 Hz were imaged using ultrasonic Doppler and optical coherence tomography methods to estimate shear dispersion. From the shear-wave speed of sound, average elastic moduli of homogeneous samples were estimated. These results are compared directly with macroscopic indentation measurements measured two ways. One set of measurements applied Hertzian theory to the loading phase of the force-displacement curves using samples treated to minimize surface adhesion forces. A second set of measurements applied Johnson Kendall-Roberts theory to the unloading phase of the force-displacement curve when surface adhesions were significant. All measurements were made using gelatin hydrogel samples of different sizes and concentrations. Agreement within 5% among elastic modulus estimates was achieved for a range of experimental conditions. Consequently, a simple quasi-static indentation measurement using a common gel can provide elastic modulus measurements that help validate dynamic shear-wave imaging estimates. PMID- 26376918 TI - A Biomechanical Study of Hyoid Bone and Laryngeal Movements During Swallowing Comparing the Blom Low Profile Voice Inner Cannula and Passy-Muir One Way Tracheotomy Tube Speaking Valves. AB - The aim of this prospective, consecutive, cohort study was to investigate the biomechanical effects, if any, of the Blom low profile voice inner cannula and Passy-Muir one-way tracheotomy tube speaking valves on movement of the hyoid bone and larynx during swallowing. Ten adult patients (8 male, 2 female) with an age range of 61-89 years (mean 71 years) participated. Criteria for inclusion were >=18 years of age, English speaking, and ability to tolerate both changing to a Blom tracheotomy tube and placement of a one-way tracheotomy tube speaking valve with a fully deflated tracheotomy tube cuff. Digitized videofluoroscopic swallow studies were performed at 30 frames/s and with each patient seated upright in the lateral plane. A total of 18 swallows (three each with 5 cc bolus volumes of single contrast barium and puree + barium * 3 conditions) were analyzed for each participant. Variables evaluated included larynx-to-hyoid bone excursion (mm), maximum hyoid bone displacement (mm), and aspiration status under three randomized conditions: 1. Tracheotomy tube open with no inner cannula; 2. Tracheotomy tube with Blom valve; and 3. Tracheotomy tube with Passy-Muir valve. Blinded reliability testing with a Pearson product moment correlation was performed on 20 % of the data. Intra- and inter-rater reliability for combined measurements of larynx-to-hyoid bone excursion and maximum hyoid bone displacement was r = 0.98. Intra- and inter-rater reliability for aspiration status was 100 %. No significant differences (p > 0.05) were found for larynx-to hyoid bone excursion and maximum hyoid bone displacement during swallowing based upon an open tracheotomy tube, Blom valve, or Passy-Muir valve. Aspiration status was identical for all three randomized conditions. The presence of a one-way tracheotomy tube speaking valve did not significantly alter two important components of normal pharyngeal swallow biomechanics, i.e., hyoid bone and laryngeal movements. Aspiration status was similarly unaffected by valve use. Clinicians should be aware that the data do not support placement of a one-way tracheotomy tube speaking valve to reduce prandial aspiration. PMID- 26376920 TI - Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis Should Be Kept in Mind in Children with Febrile Neutropenia, Oral Cavity Lesions, and Skin Rash. PMID- 26376932 TI - Comparative fingerprint analyses of extracts from the root bark of wild Hippocratea excelsa and "Cancerina" by high-performance liquid chromatography. AB - A simple high-performance liquid chromatography method was developed for the identification and comparison of quinone-methide triterpenes in wild Hippocratea excelsa and "cancerina" to establish the chromatographic profile of these compounds in root bark. The essential chromatographic conditions for this method are based on a gradient system with a reversed-phase column (C18 ) using proportions of water, methanol, and tetrahydrofuran as mobile phases to correctly separate the signals at 254 and 420 nm and compare the signals to those reported in the literature. The chromatograms exhibit good resolution and precision. Statistical analysis showed that the chromatographic profiles of wild H. excelsa and cancerina do not exhibit significant differences (p>=0.05) in their area proportions or relative retention times. The method developed in this study is suitable for the identification of the major chemotaxonomic markers of the Celastraceae family and can be used for quality control of this herbal root bark, which has uses today in Mexican folk medicine. PMID- 26376928 TI - Attenuation of Replication-Competent Adenovirus Serotype 26 Vaccines by Vectorization. AB - Replication-competent adenovirus (rcAd)-based vaccine vectors may theoretically provide immunological advantages over replication-incompetent Ad vectors, but they also raise additional potential clinical and regulatory issues. We produced replication-competent Ad serotype 26 (rcAd26) vectors by adding the E1 region back into a replication-incompetent Ad26 vector backbone with the E3 or E3/E4 regions deleted. We assessed the effect of vectorization on the replicative capacity of the rcAd26 vaccines. Attenuation occurred in a stepwise fashion, with E3 deletion, E4 deletion, and human immunodeficiency virus type 1 (HIV-1) envelope (Env) gene insertion all contributing to reduced replicative capacity compared to that with the wild-type Ad26 vector. The rcAd26 vector with E3 and E4 deleted and containing the Env transgene exhibited 2.7- to 4.4-log-lower replicative capacity than that of the wild-type Ad26 in vitro. This rcAd26 vector is currently being evaluated in a phase 1 clinical trial. Attenuation as a result of vectorization and transgene insertion has implications for the clinical development of replication-competent vaccine vectors. PMID- 26376926 TI - Long-Term Immunogenicity and Safety of a Conventional Influenza Vaccine in Patients with Type 2 Diabetes. AB - No previous studies have assessed the persistence of immune responses in individuals with diabetes. We conducted this study to evaluate the long-term immunogenicity and safety of an influenza vaccine in type 2 diabetic subjects compared with nondiabetic controls. A randomized and controlled study was conducted at two university hospitals during the 2012-2013 influenza season. The study vaccine was a standard-dose trivalent subunit inactivated intramuscular vaccine. Serum hemagglutination-inhibiting (HI) antibodies were measured at the time of vaccination and 1 month and 6 months after vaccination. Local and systemic reactions were recorded for 7 days. A total of 105 diabetic patients and 108 controls were included in the analysis. One month after vaccination, both the diabetic and nondiabetic groups satisfied all of the criteria of the Committee for Medical Products for Human Use (CHMP), and the immunogenicity profiles were statistically similar between the two groups. Although the vaccine was well tolerated, and all adverse reactions were mild to moderate, there was a tendency toward a reduced incidence of local reactions in the diabetic group. All values in the long-term immunogenicity profiles were statistically similar between the two groups, except for the seroprotection rate for the A/H1N1 influenza virus strain, which was significantly lower in the elderly diabetic group than that in the elderly nondiabetic group. However, in multivariate analysis, long-term immunogenicity was associated with age and prevaccination titer, regardless of diabetes status. (This study has been registered at CRIS [https://cris.nih.go.kr/cris/en/] under registration no. KCT0001423.). PMID- 26376935 TI - Enhancing the interlayer adhesive force in twisted multilayer MoS2 by thermal annealing treatment. AB - Few-layer MoS2 has recently gained great attention owing to its remarkable mechanical and photoelectric properties, which are strongly influenced by the interactions and relative orientations between layers. Here, we report on Raman scattering measurements of twisted MoS2 flakes prepared by exfoliation and nondestructive transfer. Thermal annealing treatment can effectively enhance the interlayer coupling of twisted MoS2 and lead to a van der Waals (vdW) interaction between two stacked layers. We have roughly calculated the interlayer coupling force by a diatomic chain model (DCM) and found that the interlayer adhesive force increased by ~20% compared with no-treatment samples. We additionally found that the non-Bernal stacking structure of MoS2 induces a weakening in the interlayer coupling. This study could promote the development of novel semiconductors, optoelectronic devices, and superlubricity materials. PMID- 26376908 TI - Nonstatin Low-Density Lipoprotein-Lowering Therapy and Cardiovascular Risk Reduction-Statement From ATVB Council. AB - Pharmacological reduction of low-density lipoprotein (LDL) cholesterol using statin drugs is foundational therapy to reduce cardiovascular disease (CVD) risk. Here, we consider the place of nonstatin therapies that also reduce LDL cholesterol in prevention of CVD. Among conventional nonstatins, placebo controlled randomized clinical trials showed that bile acid sequestrants, niacin, and fibrates given as monotherapy each reduce CVD end points. From trials in which patients' LDL cholesterol was already well controlled on a statin, adding ezetimibe incrementally reduced CVD end points, whereas adding a fibrate or niacin showed no incremental benefit. Among emerging nonstatins, monoclonal antibodies against proprotein convertase subtilisin kexin type 9 added to a statin and given for <=78 weeks showed preliminary evidence of reductions in CVD outcomes. Although these promising early findings contributed to the recent approval of these agents in Europe and in North America, much larger and longer duration outcomes studies are ongoing for definitive proof of CVD benefits. Other nonstatin agents recently approved in the United States include lomitapide and mipomersen, which both act via distinctive LDL receptor independent mechanisms to substantially reduce LDL cholesterol in homozygous familial hypercholesterolemia. We also address some unanswered questions, including measuring alternative biochemical variables to LDL cholesterol, evidence for treating children with monitoring of subclinical atherosclerosis, and potential risks of extremely low LDL cholesterol. As evidence for benefit in CVD prevention accumulates, we anticipate that clinical practice will shift toward more assertive LDL-lowering treatment, using both statins and nonstatins initiated earlier in appropriately selected patients. PMID- 26376929 TI - Proteins Selected in Leishmania (Viannia) braziliensis by an Immunoproteomic Approach with Potential Serodiagnosis Applications for Tegumentary Leishmaniasis. AB - The serodiagnosis of human tegumentary leishmaniasis (TL) presents some problems, such as the low level of antileishmanial antibodies found in most of the patients, as well as the cross-reactivity in subjects infected by other trypanosomatids. In the present study, an immunoproteomic approach was performed aimed at identification of antigens in total extracts of stationary-phase promastigote and amastigote-like forms of Leishmania (Viannia) braziliensis using sera from TL patients. With the purpose of reducing the cross-reactivity of the identified proteins, spots recognized by sera from TL patients, as well as those recognized by antibodies present in sera from noninfected patients living in areas where TL is endemic and sera from Chagas disease patients, were discarded. Two Leishmania hypothetical proteins and 18 proteins with known functions were identified as antigenic. The study was extended with some of them to validate the results of the immunoscreening. The coding regions of five of the characterized antigens (enolase, tryparedoxin peroxidase, eukaryotic initiation factor 5a, beta tubulin, and one of the hypothetical proteins) were cloned in a prokaryotic expression vector, and the corresponding recombinant proteins were purified and evaluated for the serodiagnosis of TL. The antigens presented sensitivity and specificity values ranging from 95.4 to 100% and 82.5 to 100%, respectively. As a comparative antigen, a preparation of Leishmania extract showed sensitivity and specificity values of 65.1 and 57.5%, respectively. The present study has enabled the identification of proteins able to be employed for the serodiagnosis of TL. PMID- 26376927 TI - Evaluation of Selected Borrelia burgdorferi lp54 Plasmid-Encoded Gene Products Expressed during Mammalian Infection as Antigens To Improve Serodiagnostic Testing for Early Lyme Disease. AB - Laboratory testing for the diagnosis of Lyme disease is performed primarily by serologic assays and is accurate for detection beyond the acute stage of the infection. Serodiagnostic assays to detect the early stages of infection, however, are limited in their sensitivity, and improvement is warranted. We analyzed a series of Borrelia burgdorferi proteins known to be induced within feeding ticks and/or during mammalian infection for their utility as serodiagnostic markers against a comprehensive panel of Lyme disease patient serum samples. The antigens were assayed for IgM and IgG reactivity in line immunoblots and separately by enzyme-linked immunosorbent assay (ELISA), with a focus on reactivity against early Lyme disease with erythema migrans (EM), early disseminated Lyme neuroborreliosis, and early Lyme carditis patient serum samples. By IgM immunoblotting, we found that recombinant proteins BBA65, BBA70, and BBA73 reacted with early Lyme EM samples at levels comparable to those of the OspC antigen used in the current IgM blotting criteria. Additionally, these proteins reacted with serum samples from patients with early neuroborreliosis and early carditis, suggesting value in detecting early stages of this disease progression. We also found serological reactivity against recombinant proteins BBA69 and BBA73 with early-Lyme-disease samples using IgG immunoblotting and ELISA. Significantly, some samples that had been scored negative by the Centers for Disease Control and Prevention-recommended 2-tiered testing algorithm demonstrated positive reactivity to one or more of the antigens by IgM/IgG immunoblot and ELISA. These results suggest that incorporating additional in vivo expressed antigens into the current IgM/IgG immunoblotting tier in a recombinant protein platform assay may improve the performance of early-Lyme-disease serologic testing. PMID- 26376937 TI - End-of-life care during and after an acute hospitalization in older patients with cancer, end-stage organ failure, or frailty: A sub-analysis of a prospective cohort study. AB - BACKGROUND: Many patients show deterioration in functioning and increased care needs in the last year of life. End-of-life care needs and health care utilization might differ between groups of acutely hospitalized older patients. AIM: To investigate differences in geriatric conditions, advance care planning, and health care utilization in patients with cancer, organ failure, or frailty, who died within 1 year after acute hospitalization. DESIGN: Prospective cohort study conducted between 2002 and 2008, with 1-year follow-up. SETTING: University teaching hospital in the Netherlands. PARTICIPANTS: Aged ?65 years, acutely hospitalized for ?48 h, and died within 1 year after hospitalization. At admission, all patients received a systematic comprehensive geriatric assessment. Hospital records were searched for advance care planning information and health care utilization. Differences between patient groups were calculated. RESULTS: In total, 306 patients died within 1 year after acute admission (35%) and were included; 151 with cancer, 98 with end-stage organ failure, and 57 frail older persons. At hospital admission, 72% of the frail group had delirium and/or severe pre-existing cognitive impairment. The frail and organ failure group had many pre existing disabilities. Three months post-discharge, 75% of the frail and organ failure group had died, 45% of these patients had an advance care plan in their hospital records. CONCLUSION: Patients with frailty and organ failure had highest rates of geriatric conditions at hospital admission and often had missing information on advance care planning in the hospital records. There is a need to better identify end-of-life needs for these groups. PMID- 26376921 TI - Spontaneous phenotypic suppression of GacA-defective Vibrio fischeri is achieved via mutation of csrA and ihfA. AB - BACKGROUND: Symbiosis defective GacA-mutant derivatives of Vibrio fischeri are growth impaired thereby creating a selective advantage for growth-enhanced spontaneous suppressors. Suppressors were isolated and characterized for effects of the mutations on gacA-mutant defects of growth, siderophore activity and luminescence. The mutations were identified by targeted and whole genome sequencing. RESULTS: Most mutations that restored multiple phenotypes were non null mutations that mapped to conserved domains in or altered expression of CsrA, a post-transcriptional regulator that mediates GacA effects in a number of bacterial species. These represent an array of unique mutations compared to those that have been described previously. Different substitutions at the same amino acid residue were identified allowing comparisons of effects such as at the R6 residue, which conferred relative differences in luminescence and siderophore levels. The screen revealed residues not previously identified as critical for function including a single native alanine. Most csrA mutations enhanced luminescence more than siderophore activity, which was especially evident for mutations predicted to reduce the amount of CsrA. Although CsrA mutations compensate for many known GacA mutant defects, not all CsrA suppressors restore symbiotic colonization. Phenotypes of a suppressor allele of ihfA that encodes one subunit of the integration host factor (IHF) heteroduplex indicated the protein represses siderophore and activates luminescence in a GacA-independent manner. CONCLUSIONS: In addition to its established role in regulation of central metabolism, the CsrA regulator represses luminescence and siderophore as an intermediate of the GacA regulatory hierachy. Siderophore regulation was less sensitive to stoichiometry of CsrA consistent with higher affinity for the targets of this trait. The lack of CsrA null-mutant recovery implied these mutations do not enhance fitness of gacA mutants and alluded to this gene being conditionally essential. This study also suggests a role for IHF in the GacA-CsrB CsrA regulatory cascade by potentially assisting with the binding of repressors of siderohphore and activators of luminescence. As many phosphorelay proteins reduce fitness when mutated, the documented instability used in this screen also highlights a potentially universal and underappreciated problem that, if not identified and strategically avoided, could introduce confounding variability during experimental study of these regulatory pathways. PMID- 26376934 TI - WHAT IS THE ROLE OF COMMUNITY PREFERENCE INFORMATION IN HEALTH TECHNOLOGY ASSESSMENT DECISION MAKING? A CASE STUDY OF COLORECTAL CANCER SCREENING. AB - OBJECTIVES: The aim of this study was to determine the role of community preference information from discrete choice studies of colorectal cancer (CRC) screening in health technology assessment (HTA) reports and subsequent policy decisions. METHODS: We undertook a systematic review of discrete choice studies of CRC screening. Included studies were reviewed to assess the policy context of the research. For those studies that cited a recent or pending review of CRC screening, further searches were undertaken to determine the extent to which community preference information was incorporated into the HTA decision-making process. RESULTS: Eight discrete choice studies that evaluated preferences for CRC screening were identified. Four of these studies referred to a national or local review of CRC screening in three countries: Australia, Canada, and the Netherlands. Our review of subsequently released health policy documents showed that while consideration was given to community views on CRC, policy was not informed by discrete choice evidence. CONCLUSIONS: Preferences and values of patients are increasingly being considered "evidence" to be incorporated into HTA reports. Discrete choice methodology is a rigorous quantitative method for eliciting preferences and while as a methodology it is growing in profile, it would appear that the results of such research are not being systematically translated or integrated into HTA reports. A formalized approach is needed to incorporate preference literature into the HTA decision-making process. PMID- 26376925 TI - Understanding the Association of Human Rhinovirus with Asthma. AB - Human rhinoviruses are ubiquitous seasonal pathogens. They have known associations with first onset of wheezing illnesses in children and with asthma exacerbations in patients of all ages. It is not yet certain whether human rhinoviruses play a direct role in the pathogenesis of asthma by activating deleterious inflammatory responses or if they only serve as a catalyst to accelerate the disease in genetically predisposed individuals. There have been previously demonstrated reductions in the development of the asthmatic phenotype with passive immunization against respiratory syncytial virus; however, in the case of rhinovirus, there are barriers to effective vaccine development, such as the lack of a common antigenic target due to alterations of surface markers among subtypes. It remains to be determined whether certain subtypes of human rhinovirus are more asthmagenic and therefore worthy of greater attention as vaccine candidates, but several studies have suggested that RV-C and certain RV-A strains may be more strongly linked with asthma. PMID- 26376939 TI - REACT expanded-access program in patients with metastatic renal cell carcinoma: real-world data from a European subanalysis. AB - AIM: RAD001 Expanded Access Clinical Trial (REACT) provided everolimus to patients with metastatic RCC before its commercial availability. This retrospective subgroup analysis evaluated eventual differences, mainly in safety, between the large European population (n = 906; 66.3%) and the overall population (n = 1367). PATIENTS & METHODS: REACT enrolled patients from 34 countries who received everolimus 10 mg/day until progression/discontinuation or commercial availability. RESULTS: Baseline characteristics, except race/ethnicity, were similar. Incidences of grade 3/4 adverse events were 50.7/11.3% in the European population and 48.8/12.8% in the overall population. A similar percentage of the European and overall populations achieved stable disease (~ 51%) and completed treatment (20.6 and 19.7%). CONCLUSION: These results do not suggest differences for the European population and support everolimus as a worldwide standard of care for VEGFR-refractory metastatic RCC (NCT00655252). PMID- 26376936 TI - Spiritual history taking in palliative home care: A cluster randomized controlled trial. AB - BACKGROUND: Many health-care providers experience barriers to addressing spiritual needs, such as not having the right vocabulary. The ars moriendi model might be a feasible tool for spiritual history taking in palliative care. AIM: To investigate the effect of a structured spiritual history taking on the spiritual well-being of palliative patients in home care. DESIGN: Cluster randomized controlled trial, conducted between February and October 2013. PATIENTS AND METHODS: Registered nurses and general practitioners approached eligible patients with an incurable, life-threatening disease for study participation. Health-care providers allocated to the intervention arm of the study took a spiritual history on the basis of the ars moriendi model. Health-care providers in the control arm provided care as usual. Patient-reported outcomes on spiritual well-being, quality of life, pain, and patient-provider trust were assessed at two points in time. RESULTS: A total of 245 health-care providers participated in the study (204 nurses and 41 physicians). In all, 49 patient-provider dyads completed the entire study protocol. The median age of the patients was 75 years (range: 41-95 years), and 55% of the patients were female. There were no significant differences at any point in time in the scores on spiritual well-being, quality of life, pain, or patient-provider trust between the intervention and the control group. CONCLUSION: This cluster randomized controlled trial showed no demonstrable effect of spiritual history taking on patient scores for spiritual well-being, quality of life, health-care relationship trust, or pain. Further research is needed to develop instruments that accurately assess the effectiveness of spiritual interventions in palliative care populations. PMID- 26376930 TI - Human Memory CD4+ T Cell Immune Responses against Giardia lamblia. AB - The intestinal protozoan parasite Giardia lamblia may cause severe prolonged diarrheal disease or pass unnoticed as an asymptomatic infection. T cells seem to play an important role in the immune response to Giardia infection, and memory responses may last years. Recently, TH17 responses have been found in three animal studies of Giardia infection. The aim of this study was to characterize the human CD4(+) T cell responses to Giardia. Peripheral blood mononuclear cells (PBMCs) were obtained from 21 returning travelers with recent or ongoing giardiasis and 12 low-risk healthy controls and stimulated in vitro with Giardia lamblia proteins. Production of tumor necrosis factor alpha (TNF-alpha), gamma interferon, interleukin-17A (IL-17A), IL-10, and IL-4 was measured in CD4(+) effector memory (EM) T cells after 24 h by flow cytometry. After 6 days of culture, activation and proliferation were measured by flow cytometry, while an array of inflammatory cytokine levels in supernatants were measured with multiplex assays. We found the number of IL-17A-producing CD4(+) EM T cells, as well as that of cells simultaneously producing both IL-17A and TNF-alpha, to be significantly elevated in the Giardia-exposed individuals after 24 h of antigen stimulation. In supernatants of PBMCs stimulated with Giardia antigens for 6 days, we found inflammation-associated cytokines, including 1L-17A, as well as CD4(+) T cell activation and proliferation, to be significantly elevated in the Giardia-exposed individuals. We conclude that symptomatic Giardia infection in humans induces a CD4(+) EM T cell response of which IL-17A production seems to be an important component. PMID- 26376940 TI - Diet-induced neuropeptide expression: feasibility of quantifying extended and highly charged endogenous peptide sequences by selected reaction monitoring. AB - Understanding regulation and action of endogenous peptides, especially neuropeptides, which serve as inter- and intracellular signal transmitters, is key in understanding a variety of functional processes, such as energy balance, memory, circadian rhythm, drug addiction, etc. Therefore, accurate and reproducible quantification of these bioactive endogenous compounds is highly relevant. The biosynthesis of endogenous peptides, involving multiple possible trimming and modification events, hinders the de novo prediction of the active peptide sequences, making MS-based measurements very valuable in determining the actual active compounds. Here, we report an extended selected reaction monitoring (SRM)-based strategy to reproducibly and quantitatively monitor the abundances of a set of 15 endogenously occurring peptides from Rattus norvegicus hypothalamus. We demonstrate that SRM can be extended toward reproducible detection and quantification of peptides, bearing characteristics very different from tryptic peptides. We show that long peptide sequences, producing precursors with up to five and MS2 fragment ions with up to three charges, can be targeted by SRM on a triple quadrupole instrument. Using this approach to quantify endogenous peptide levels in hypothalami of animals subjected to different diets revealed several significant changes, most notably the significant upregulation of VGF-derived signaling peptide AQEE-30 upon high caloric feeding. PMID- 26376931 TI - Reduced Transplacental Transfer of a Subset of Epstein-Barr Virus-Specific Antibodies to Neonates of Mothers Infected with Plasmodium falciparum Malaria during Pregnancy. AB - Over 35% of children in a region of malaria endemicity are infected with Epstein Barr virus (EBV) by 6 months of age. This susceptibility may be linked to impaired transplacental transfer of antibodies. In this study, we determined the effect of malaria exposure during pregnancy on the transfer of EBV-specific maternal antibodies in a region of western Kenya that experiences endemic malaria. Pregnant mothers were recruited and followed up until delivery to determine levels of neonatal malaria exposure. Levels of EBV lytic (viral capsid antigen [VCA], Z transcriptional activator [Zta], and early diffuse antigen complex [EAd]) and EBV latent (EBV nuclear antigen-1 (EBNA1]) and tetanus specific IgG antibodies were measured in 70 paired maternal and cord blood samples using a Luminex-bead-based assay. A high proportion (63%) of the infants were exposed to malaria in utero. Levels of EBV- and tetanus-specific antibodies were similar in malaria-infected mothers and in mothers who had no detectable malaria infection. Malaria-exposed neonates had significantly lower levels of anti-EBNA1, anti-Zta, and anti-EAd antibodies than were seen in their mothers. In utero malaria exposure resulted in significant reductions in transplacental transfer of anti-VCA-p18 and anti-EBNA1 antibodies of 13% and 22%, respectively. Neonates received significantly low levels of anti-Zta and anti-EAd antibodies irrespective of malaria exposure levels. In multivariate analysis, in utero malaria exposure was associated with a significant reduction in the transfer of anti-VCA-p18 and anti-EBNA1 antibodies to the neonates (P = 0.0234 and P = 0.0017, respectively). Malaria during pregnancy results in differential levels of transfer of EBV-specific antibodies from the mother to the fetus. The impaired transplacental transfer of some antibodies may lead to the malaria-exposed neonates being susceptible to early EBV infection. PMID- 26376945 TI - Obesity and Hyperlipidemia Modulate Alveolar Bone Loss in Wistar Rats. AB - BACKGROUND: A positive association between obesity-associated metabolic disorders (e.g., hyperlipidemia and diabetes) and periodontitis has been demonstrated in the literature. This study evaluates the role of cafeteria diet-induced obesity/hyperlipidemia (CAF) on alveolar bone loss (ABL) in rats. METHODS: Sixty male Wistar rats were randomly divided in four groups: control, periodontitis (PERIO), obesity/hyperlipidemia (CAF), and obesity/hyperlipidemia plus periodontitis (CAF+PERIO). Groups CAF and CAF+PERIO were exposed to a high-fat, hypercaloric diet. At week 12, periodontal disease was induced in groups PERIO and CAF+PERIO by ligatures in the upper second molar. The contralateral tooth was considered the intragroup control. Body weight and Lee index were evaluated weekly during the experiment. Serum glucose and cholesterol/triglycerides in the liver were evaluated, and percentage of ABL was measured by microcomputed tomography. Serum tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta were evaluated by enzyme-linked immunosorbent assay at week 17. RESULTS: Body weight, Lee index, and cholesterol/triglycerides in the liver increased in groups exposed to the cafeteria diet. Groups PERIO and CAF+PERIO exhibited a significantly higher ABL compared to control and CAF groups. The presence of obesity and hyperlipidemia significantly increased ABL in the CAF+PERIO group compared to the PERIO group (53.60 +/- 3.44 versus 42.78 +/- 7.27, respectively) in the sides with ligature. Groups exposed to CAF exhibited higher ABL in the sides without ligature. No differences were observed among groups for IL-1beta and TNF-alpha. CONCLUSION: Obesity and hyperlipidemia modulate the host response to challenges in the periodontium, increasing the expression of periodontal breakdown. PMID- 26376943 TI - Serum Lipids in Turkish Patients with beta-Thalassemia Major and beta-Thalassemia Minor. PMID- 26376933 TI - Family stress moderates relations between physiological and behavioral synchrony and child self-regulation in mother-preschooler dyads. AB - From a bio-behavioral framework, the relations between physiological synchrony, positive behavioral synchrony, and child self-regulation under varying levels of risk were examined among 93 mother- (M age = 30.44 years, SD = 5.98 years) preschooler (M age = 3.47 years, SD =.52 years, 58.70% male) dyads. Physiological synchrony was examined using interbeat interval (IBI) data and measures of positive behavioral synchrony and self-regulation were based on observations of a mother-child interaction task. Results supported the phenomenon of physiological synchrony among mother-preschooler dyads during an interaction, but not a baseline, task. Moderation analyses indicated that under conditions of high family risk, positive behavioral synchrony and child self-regulation were greater when physiological synchrony was low. Positive behavioral synchrony was positively associated with child self-regulation, regardless of risk status. The results document physiological synchrony among mothers and their preschool-aged children and the complex ways that physiological attunement relates to important developmental processes. PMID- 26376942 TI - Biomimetic vaterite formation at surfaces structurally templated by oligo(glutamic acid) peptides. AB - Previous studies have reported that the metastable vaterite phase of calcium carbonate can be stabilized in solution by acidic additives. Here we demonstrate that vaterite can also be stabilized directly at surfaces by engineered peptides. Our data show that the mineralisation occurs in a 'self-templating' process where calcium ions restructure the peptide backbone, which in turn allows for effective vaterite precipitation. PMID- 26376944 TI - Scaling and Root Planing per Quadrant Versus One-Stage Full-Mouth Disinfection: Assessment of the Impact of Chronic Periodontitis Treatment on Quality of Life--A Clinical Randomized, Controlled Trial. AB - BACKGROUND: There are few randomized, controlled clinical trials about the effect of non-surgical periodontal treatment on oral health-related quality of life (OHRQL). This study aims to compare the effects of two different forms of non surgical periodontal therapy, scaling and root planing (SRP) per quadrant and one stage full-mouth disinfection (FMD), on periodontal clinical parameters and OHRQL of patients with chronic periodontitis. METHODS: In this randomized, controlled clinical trial, the questionnaires Oral Impacts on Daily Performance (OIDP) and Oral Health and Quality of Life (OHQoL) were given to 90 patients divided into two groups: SRP (n = 45) and FMD (n = 45). Periodontal clinical parameters recorded included probing depth, clinical attachment level, plaque index, and gingival index. For statistical analysis, chi(2) test, Fisher exact test, Mann Whitney U test, and Wilcoxon test were used. Intention-to-treat analyses were performed at T0 (baseline) for periodontal clinical parameters, T1 (30 days after treatment) for questionnaires, and T2 (180 days after treatment) for both. RESULTS: No significant differences were identified between the SRP and FMD groups in regard to OHQoL and OIDP scores when comparing the data of T1 and T2. CONCLUSION: Patients treated by both SRP and FMD showed improvement in all periodontal clinical parameters and OHRQL, with no significant differences between treatment groups. PMID- 26376941 TI - Tripling the maximum imaging depth with third-harmonic generation microscopy. AB - The growing interest in performing high-resolution, deep-tissue imaging has galvanized the use of longer excitation wavelengths and three-photon-based techniques in nonlinear imaging modalities. This study presents a threefold improvement in maximum imaging depth of ex vivo porcine vocal folds using third harmonic generation (THG) microscopy at 1552-nm excitation wavelength compared to two-photon microscopy (TPM) at 776-nm excitation wavelength. The experimental, analytical, and Monte Carlo simulation results reveal that THG improves the maximum imaging depth observed in TPM significantly from 140 to 420 MUm in a highly scattered medium, reaching the expected theoretical imaging depth of seven extinction lengths. This value almost doubles the previously reported normalized imaging depths of 3.5 to 4.5 extinction lengths using three-photon-based imaging modalities. Since tissue absorption is substantial at the excitation wavelength of 1552 nm, this study assesses the tissue thermal damage during imaging by obtaining the depth-resolved temperature distribution through a numerical simulation incorporating an experimentally obtained thermal relaxation time (tau). By shuttering the laser for a period of 2tau, the numerical algorithm estimates a maximum temperature increase of ~2 degrees C at the maximum imaging depth of 420 MUm. The paper demonstrates that THG imaging using 1552 nm as an illumination wavelength with effective thermal management proves to be a powerful deep imaging modality for highly scattering and absorbing tissues, such as scarred vocal folds. PMID- 26376946 TI - Activation of Receptor Activator of Nuclear Factor-kappaB Ligand and Matrix Metalloproteinase Production in Periodontal Fibroblasts by Endothelin Signaling. AB - BACKGROUND: Periodontitis is a group of inflammatory diseases affecting the tissues supporting the teeth that will progressively cause the loss of alveolar bone and periodontal ligaments and eventually the dentition. Activation of osteoclast activity by receptor activator of nuclear factor-kappaB ligand (RANKL) and released enzymes such as matrix metalloproteinases (MMPs) are among the factors involved in the breakdown of the periodontium. However, the mechanisms regulating their production in periodontitis are poorly understood. Endothelin signaling via the activation of the endothelin-A receptor (EDNRA) by endothelin-1 may play a role in the disease because the expression of the receptor and ligand is elevated in the periodontal tissues of patients with periodontitis. METHODS: Cultured primary human periodontal fibroblasts were treated with 20 and 100 nM endothelin-1 for 6 and 24 hours and then collected to assess MMP and RANKL production by immunoblotting. Inhibitors were used to identify the molecular pathways activated by EDNRA in these cells. RESULTS: Endothelin-1 stimulated the production of MMP1, MMP8, and RANKL in a dose- and time-dependent manner; blocking EDNRA function with the antagonist TBC3214 inhibited the response, although EDNRA activation had no effects on osteoprotegerin production. These mechanistic studies indicate that EDNRA activates phospholipase C, which then 1) increases the MMP1 protein levels through activation of the extracellular signal regulated kinase mitogen-activated protein kinase-dependent pathway and 2) upregulates RANKL by a different pathway. CONCLUSION: These results suggest that EDNRA may function in the breakdown of the periodontal tissues associated with periodontitis by promoting the protein expression of MMPs and RANKL via the phospholipase C pathway. PMID- 26376938 TI - Is It Possible to Predict Pulmonary Complications and Mortality in Hematopoietic Stem Cell Transplantation Recipients from Pre-Transplantation Exhaled Nitric Oxide Levels? AB - OBJECTIVE: Chemo/radiotherapy-induced free oxygen radicals and reactive oxygen derivatives contribute to the development of early and late transplantation related pulmonary and extra-pulmonary complications in hematopoietic stem cell transplantation (HSCT) recipients. It has been proposed that an increase in fractional exhaled nitric oxide (FeNO) level indicates oxidative stress and inflammation in the airways. The aim of this prospective study is to evaluate the pre-transplantation FeNO levels in HSCT patients and to search for its role in predicting post-transplantation pulmonary complications and mortality. MATERIALS AND METHODS: HSCT patients were included in the study prospectively between October 2009 and July 2011. Pre-transplantation FeNO levels were measured with a NIOX MINO(r) device prior to conditioning regimens. All patients were monitored prospectively for post-transplantation pulmonary complications with medical history, physical examination, chest X-ray, and pulmonary function tests. RESULTS: A total of 56 patients (33 autologous, 23 allogeneic) with mean age of 45+/-13 years were included in the study, among whom 40 (71%) were male. Pre transplantation FeNO level of the whole study group was found to be 24+/-13 (mean +/- standard deviation) parts per billion (ppb). The FeNO level in allogeneic HSCT recipients was 19+/-6 ppb while it was 27+/-15 ppb in autologous HSCT recipients (p=0.042). No significant correlation was found between the pre transplantation chemotherapy and radiotherapy protocols and baseline FeNO levels (p>0.05). Post-transplantation pulmonary toxicity was identified in 12 (21%) patients and no significant relationship was found between baseline FeNO levels and pulmonary toxicity. The survival rate of the whole study group for 1 year after transplantation was 70%. No significant relationship was identified between baseline FeNO values and survival (FeNO 19+/-7 ppb in patients who died and 26+/ 15 ppb in the survivors; p=0.114). CONCLUSION: Pre-transplantation FeNO measurement does not seem to have a role in predicting post-transplantation pulmonary complications and mortality. PMID- 26376947 TI - Early urinary biomarkers for renal tubular damage in spontaneously hypertensive rats on a high salt intake. AB - A high salt intake exacerbates hypertension and accelerates renal tubular damage in hypertensive patients. However, data concerning early biomarkers for renal tubular change induced by a high salt intake are limited. The objective of this study was to clarify the time course of new biomarkers for renal tubular damage during high salt intake in spontaneously hypertensive rats (SHR). Male SHR received a regular or high-salt diet from 9 to 17 weeks of age. At 10 weeks of age, a high salt intake caused renal tubular damage, which was further exacerbated at 17 weeks of age. Although albuminuria was detected in salt-loaded SHR at 14 weeks of age, urinary excretion of vanin-1 and neutrophil gelatinase associated lipocalin (NGAL) was elevated in these animals from 10-17 weeks of age. However, kidney injury molecule-1 (Kim-1) was elevated at 15 weeks of age in salt-loaded SHR. These results suggest that urinary vanin-1 and NGAL are potentially early biomarkers for renal tubular damage in SHR under a high salt intake. PMID- 26376951 TI - The electronic and optical properties of MoS(2(1-x))Se(2x) and MoS(2(1-x))Te(2x) monolayers. AB - In a very recent article, atomically thin two-dimensional MoS2xSe2(1-x) nanosheets have been synthesized with complete composition tunability using a temperature gradient assisted chemical vapor deposition technique [J. Am. Chem. Soc., 2014, 136, 3756]. To have a better understanding of the composition dependent tunability of the properties of this class of materials we here perform first principles calculations on the detailed electronic structure of single layered transition metal dichalcogenides MoS2(1-x)Se2x and MoS2(1-x)Te2x. The positive value of mixing energy of both MoS2(1-x)Se2x and MoS2(1-x)Te2x 2D sheets at various composition confirms their formation at some energy cost. The analysis of the composition dependent band structure and the density of states of these 2D sheets reveals certain interesting features. The band gap variation of the MoS2(1 x)Se2x nanosheets is almost linear with composition while that of MoS2(1-x)Te2x deviates slightly from linearity. We have also calculated the optical absorption spectrum of these nanosheets as a function of composition and found that the optical transitions are mainly metal d-d type spin forbidden transitions. PMID- 26376949 TI - Correction: Supramolecular metallacycles with a 'pseudo double-paracyclophane' structure based on flexible pi-conjugated linkers. AB - Correction for 'Supramolecular metallacycles with a 'pseudo double paracyclophane' structure based on flexible pi-conjugated linkers' by W. Shen et al., Chem. Commun., 2015, 51, 11560-11563. PMID- 26376952 TI - Reactivity, swelling and aggregation of mixed-size silicate nanoplatelets. AB - Montmorillonite is a key ingredient in a number of technical applications. However, little is known regarding the microstructure and the forces between silicate platelets. The size of montmorillonite platelets from different natural sources can vary significantly. This has an influence on their swelling behavior in water as well as in salt solutions, particularly when tactoid formation occurs, that is when divalent counterions are present in the system. A tactoid consists of a limited number of platelets aggregated in a parallel arrangement with a constant separation. The tactoid size increases with platelet size and with very small nanoplatelets, ~30 nm, no tactoids are observed irrespectively of the platelet origin and concentration of divalent ions. The formation and dissociation of tactoids seem to be reversible processes. A large proportion of small nanoplatelets in a mixed-size system affects the tactoid formation, reduces the aggregation number and increases the extra-lamellar swelling in the system. PMID- 26376957 TI - Lateral capillary interactions between colloids beneath an oil-water interface that are driven by out-of-plane electrostatic double-layer interactions. AB - We study the lateral capillary interactions between colloids beneath an oil-water interface that lead to closely packed two-dimensional self-assembled colloidal crystals. These capillary forces are caused by the overlap of deformed interfaces above colloids on a solid substrate. The interface deformation is due to the electrostatic disjoining pressure between the charged particles and the charged oil-water interface. It is notable that the short-range (i.e., on the nanometer scale) and out-of-plane electrostatic double-layer interactions, which occur through an aqueous phase, can generate the long-range lateral capillary attraction (i.e., on the micrometer scale). PMID- 26376954 TI - Metabolism, Distribution, and Elimination of Mequindox in Pigs, Chickens, and Rats. AB - Mequindox (MEQ), a quinoxaline-N,N-dioxide antibacterial agent used to control bacterial enteritis in various food-producing animals, is a potential violative residue in food animal-derived products. The disposition and elimination of MEQ in rats, pigs, and chickens was comprehensively investigated to identify the marker residue and target tissue of MEQ in food animals for residue monitoring. Following a single oral administration, 62-71% of MEQ was rapidly excreted via urine and feces in all species within 24 h. Urinary excretion of radioactivity was 84 and 83.5% of the administered dose in rats and pigs, respectively. More than 92% of the administered dose was excreted in all species within 15 days. Radioactivity was found in nearly all tissues at the first 6 h after dosing, with the majority of radioactivity cleared within 4-6 days. The highest radioactivity and longest persisting time were found to be in the liver and kidney. Totals of 11, 12, and 7 metabolites were identified in rats, chickens, and pigs, respectively. No parent drug could be detected in any of the tissues of pigs and chickens. 3-Methyl-2-acetyl quinoxaline (M1), 3-methyl-2-(1-hydroxyethyl) quinoxaline-N4-monoxide (M4), and 3-methyl-2-(1-hydroxyethyl) quinoxaline-1,4 dioxide (M6) were the common and major metabolites of MEQ in all three species. Additionally, 3-methyl-2-(1-hydroxyethyl) quinoxaline (M5), 3-hydroxymethyl-2 ethanol quinoxaline-1,4-dioxide (M7), and 3-methyl-2-(1-hydroxyethyl) quinoxaline N1-monoxide (M8) were the major metabolites of MEQ in rats, pigs, and chickens, respectively. M1 was designated to be the marker residue of MEQ in pigs and chickens. These results provide scientific data for the determination of marker residues and withdrawal time of MEQ in food animals and improve the understanding of the toxicity and disposition of MEQ in animals. PMID- 26376953 TI - Effect of patellar strap and sports tape on pain in patellar tendinopathy: A randomized controlled trial. AB - Numerous athletes with patellar tendinopathy (PT) use a patellar strap or sports tape during sports. This study's aim was to investigate the short-term effect of these orthoses on patellar tendon pain. Participants performed the single-leg decline squat, vertical jump test, and triple-hop test under four different conditions (patellar strap, sports tape, placebo, and control). Subsequently, participants practiced sports as usual for 2 weeks; during 1 week, they were assigned to one of the four conditions. Pain was measured with the visual analog scale (VAS). In total, 97 athletes with PT [61% male, age 27.0 (SD8.1), VISA-P 58.5 (SD12.7)] were analyzed. On the single-leg decline squat, the VAS pain score reduced significantly in the patellar strap (14 mm, P = 0.04) and the sports tape condition (13 mm, P = 0.04), compared with control, but not placebo. A significant decrease in VAS pain during sports was found in the sports tape (7 mm, P = 0.04) and placebo group (6 mm, P = 0.04). The VAS pain score two hours after sports decreased significantly in the patellar strap, sports tape and placebo group (8-mm, P < 0.001, 10 mm, P = 0.001 and 7 mm, P = 0.03, respectively). This study's findings indicate that an orthosis (including placebo tape) during sports can reduce pain in PT patients in the short term. PMID- 26376948 TI - Elevated vasoinhibin derived from prolactin and cathepsin D activities in sera of patients with preeclampsia. PMID- 26376950 TI - Cholinesterase of rats experimentally infected by Cryptococcus neoformans: Relationship between inflammatory response and pathological findings. AB - The aim of this study was to assess the role of the acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) as biomarkers of inflammation and tissue injury on rats experimentally infected by Cryptococcus neoformans. For this purpose, 20 male rats were divided into two groups: 10 animals representing the uninfected control group (Group A) and 10 C. neoformans var. grubii infected animals (Group B). Blood and brain samples were collected on days 10 (A10 and B10), and 30 (A30 and B30) post-infection (PI) for hematological analyses; AChE (in lymphocytes and brain) and seric BChE activity; interleukins (IL-1, IL-6, and IL-10); nitrite/nitrate (NOx) levels; and markers of protein oxidation (AOPP) and lipid peroxidation (TBARS). As a result, when animals of Group A were compared to animals of Group B, it was observed leukocytosis (P<0.05) on day 10 PI; AChE activity increase (P<0.05) in lymphocytes (day 30 PI) and in brain (days 10 and 30 PI); BChE activity decrease (P<0.05) on day 10 PI; IL-1 and IL-6 increase (P<0.01) in both periods, while IL-10 had reduced levels (P<0.01) in the same periods; NOx levels increased (P<0.05) significantly on days 10 and 30 PI, while AOPP and TBARS levels increased significantly on day 30 PI; as well as pneumonia on infected rats. Therefore, based on the results obtained, it was possible to conclude that AChE and BChE behavior lead to a proinflammatory reaction evidenced by the enhancement of IL-1, IL-6, and NOx throughout the experiment associated with reduction on IL-10 levels, and cellular damage. PMID- 26376964 TI - Societies can both grow old and lower dementia burden. PMID- 26376956 TI - Homocysteine excess: delineating the possible mechanism of neurotoxicity and depression. AB - Homocysteine (Hcy) is a nonproteogenic sulfur containing amino acid derived from dietary methionine through demethylation. Homocysteine can be re-methylated to methionine [precursor of S-adenosylmethionine (SAM)] via the re-methylation or 5 methyltetrahydrofolate pathway or undergoes transsulfuration to form cysteine by the action of metabolic enzymes and cofactors. Impaired metabolism due to genetic alteration in metabolic enzymes (methionine synthase, methyltetrahydrofolate reductase (MTHFR), cystathionine beta-synthase (CbetaS), and cystathionine-gamma lyase (CgammaL) or deficiency in cofactors (vitamin B6 , B12 , folate) may lead to acquired metabolic anomaly known as hyperhomocysteinemia. Hcy excess decreases the S-adenosylmethionine (SAM)-dependent synthesis of catecholamines, viz. dopamine, norepinephrine, epinephrine, and noncatecholamine, viz. serotonin (5 HT), due to genetic alteration in key enzyme MTHFR in the homocysteine metabolism pathway that leads to depression. Thus, hyperhomocysteinemia (HHcy)-induced SAM level is influenced by the single nucleotide polymorphism (SNP) MTHFR C677T. Furthermore, HHcy leads to production of precarious neurotoxic product homocysteic acid (HCA) and cysteine sulfinic acid (CSA) which acts as an N-methyl D-aspartate (NMDA) receptor agonist and has neurotoxic effects on dopaminergic neurons. In the current review, an attempt has been made to discuss the neurotoxic effects of HHcy in the pathogenesis of depression. PMID- 26376963 TI - Immunotherapy of Melanoma. AB - The history of immunotherapy is rooted in the treatment of melanoma and therapy with immune checkpoint-blocking agents is now a cornerstone for the treatment of metastatic melanoma. The first effective immunotherapies approved by the US Food and Drug Administration in melanoma included interleukin-2 for metastatic disease and interferon alpha in the adjuvant setting. These were followed by a group of new therapies, including checkpoint-blocking antibodies targeting cytotoxic T lymphocyte-associated protein 4 and programmed cell death protein 1. Therapies intended to 'reeducate' T cells, such as tumor-infiltrating lymphocyte therapy, oncolytic viruses and tumor vaccines, have yielded promising results and are under development. Finally, the integration of the above therapies as well as development of new coinhibitory and costimulatory agents, though in early stages, appear very promising and likely represent the next phase in drug development for the treatment of metastatic melanoma. PMID- 26376965 TI - Multitarget disease-modifying therapy in Parkinson's disease? PMID- 26376959 TI - Hyperuricemia is independently associated with left ventricular hypertrophy in post-menopausal women but not in pre-menopausal women in rural Northeast China. AB - The aim of this article is to estimate the relationship between hyperuricemia and left ventricular hypertrophy (LVH) and to investigate whether menopause was associated with the relationship between hyperuricemia and LVH. This survey was conducted from July 2012 to August 2013. A total of 6029 women (3508, 58.2% were post-menopause) from the rural Northeast China were randomly selected and examined. LVH was defined using the 2007 Guidelines for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Age, body mass index, glucose, estimated glomerular filtration rate and lipid level were significantly correlated with serum uric acid level. LVH showed a gradual increase in accordance with the serum uric acid level in entire study population (<4.0 mg/dL, 11.4%; 4 to <5 mg/dL, 14.9%; 5 to <6 mg/dL, 18.9%; >=6 mg/dL, 27.4%; p < 0.001). Multivariate analysis revealed that hyperuricemia was a significantly independent risk factor for LVH in post-menopausal women [OR (95% CI): 1.367 (1.026, 1.821)], but not in pre menopausal women [OR (95% CI): 1.290 (0.669, 2.486)]. These findings suggested that hyperuricemia can be used as a risk marker of LVH in a female population and, in particular, as an independent risk factor in post-menopausal women but not in pre-menopausal women. PMID- 26376960 TI - Early life urban exposure as a risk factor for developing obesity and impaired fasting glucose in later adulthood: results from two cohorts in Thailand. AB - BACKGROUND: Obesity and obesity related conditions, driven by processes such as urbanization and globalization, are contributing to pronounced cardiovascular morbidity and mortality in developing countries. There is limited evidence on the influence of living in an urban environment in early life on obesity and obesity related conditions later in life in developing countries such as Thailand. METHODS: We used data from two cohort studies conducted in Thailand, the Thai Cohort Study (TCS) and the Chiang Mai University (CMU) Health Worker Study, to investigate the association between early life urban (vs rural) exposure and the later development of obesity. We additionally explored the association between early life urban exposure and impaired fasting glucose in adulthood using data from the CMU Health Worker Study. RESULTS: Among 48,490 adults from the TCS, 9.1 % developed obesity within 4 years of follow-up. Among 1,804 initially non-obese adults from CMU Health worker study, 13.6 % developed obesity within 5 years of follow-up. Early life urban exposure was associated with increased risk of developing obesity in adulthood in both cohorts. Adjusting for age and sex, those who spent their early lives in urban areas were 1.21 times more likely to develop obesity in the TCS (OR 1.21, 95 % CI 1.12 to 1.31) and 1.65 times more likely in the CMU Health Worker study (OR 1.65, 95 % CI 1.23 to 2.20). These associations remained significant despite adjustment for later life urban exposure and current household income. No evidence for an association was found for impaired fasting glucose. CONCLUSIONS: Early life urban exposure was associated with increased risk of developing obesity in adulthood. These findings support public health intervention programs to prevent obesity starting from early ages. PMID- 26376958 TI - A phase II study of AT9283, an aurora kinase inhibitor, in patients with relapsed or refractory multiple myeloma: NCIC clinical trials group IND.191. PMID- 26376961 TI - Dietary Intake Patterns Are Consistent Across Seasons in a Cohort of Healthy Adults in a Metropolitan Population. AB - BACKGROUND: Current literature provides conflicting data regarding seasonal variability in dietary intake. OBJECTIVE: Our aim was to examine seasonal variation in dietary intake in healthy adults from the metropolitan Washington, DC, area. DESIGN: This study utilized an observational cohort design. PARTICIPANTS/SETTING: Male and female healthy volunteers (n=103) between the ages of 18 and 75 years were recruited from the metropolitan Washington, DC, area to participate in a clinical study at the National Institutes of Health Clinical Center from February 2011 to June 2014. MAIN OUTCOME MEASURES: Three- to seven day food records were collected from subjects (n=76) at three time points (12 to 15 weeks apart). Subjects were excluded from analysis (n=27) if they completed less than three time points. Food records were reviewed by nutrition staff, assigned to a season, and coded in Nutrient Data System for Research for energy, macronutrient, micronutrient, and food-group serving analysis. STATISTICAL ANALYSES: Multivariate general linear models were run on energy, macronutrient, micronutrient, and food-group intakes, while being adjusted for age, sex, race, and body mass index (calculated as kg/m(2)). RESULTS: Subjects had a mean+/ standard deviation body mass index of 25+/-3.9 and age of 34+/-12.4 years. Subject demographics were 71.1% white, 9.2% black/African American, 13.2% Asian, and 6.6% unknown race, with 44.7% males and 55.3% females. Mean intake of energy across seasons was 2,214.6+/-623.4 kcal with 17.3%+/-4.1%, 33.6%+/-5.5%, 46.6%+/ 8.0%, and 2.7%+/-3.2% of calories from protein, fat, carbohydrate, and alcohol, respectively. Intakes of energy, macronutrients, micronutrients, and food groups did not differ between seasons. CONCLUSIONS: People living in the metropolitan Washington, DC, area did not exhibit seasonal variation in dietary intake. Therefore, when designing studies of nutrient intake in a metropolitan population, these findings suggest that investigators do not need to consider the season during which diet is examined. PMID- 26376967 TI - Plugging epilepsy knowledge gaps in Cameroon. PMID- 26376966 TI - Implications of the discovery of brain lymphatic pathways. PMID- 26376968 TI - New therapeutic approaches for the prevention and treatment of migraine. AB - The management of patients with migraine is often unsatisfactory because available acute and preventive therapies are either ineffective or poorly tolerated. The acute treatment of migraine attacks has been limited to the use of analgesics, combinations of analgesics with caffeine, ergotamines, and the triptans. Successful new approaches for the treatment of acute migraine target calcitonin gene-related peptide (CGRP) and serotonin (5-hydroxytryptamine, 5 HT1F) receptors. Other approaches targeting the transient receptor potential vanilloid (TRPV1) receptor, glutamate, GABAA receptors, or a combination of 5 HT1B/1D receptors and neuronal nitric oxide synthesis have been investigated but have not been successful in clinical trials thus far. In migraine prevention, the most promising new approaches are humanised antibodies against CGRP or the CGRP receptor. Non-invasive and invasive neuromodulation approaches also show promise as both acute and preventive therapies, although further studies are needed to define appropriate candidates for these therapies and optimum protocols for their use. PMID- 26376955 TI - Early lenalidomide treatment for low and intermediate-1 International Prognostic Scoring System risk myelodysplastic syndromes with del(5q) before transfusion dependence. AB - Lenalidomide is approved for the treatment of transfusion-dependent (TD) del(5q) myelodysplastic syndromes (MDS). However, few data are available in patients with transfusion-independent (TI) del(5q) MDS. In the first, observational, part of this 2-part study, we assessed the impact of transfusion dependence on overall survival (OS) and non-leukemic death in untreated del(5q) MDS patients who were TD (n = 136), TI with hemoglobin (Hb) >=10 mg/dL (n = 88), or TI with Hb <10 mg/dL (n = 96). In the second, interventional, part we assessed the quality-of life (QoL) benefits and clinical efficacy of lenalidomide (10 mg/day) in 12 patients with TI del(5q) MDS and Hb <10 mg/dL. In the untreated population, OS was significantly longer in TI than in TD patients (TI [Hb >=10 g/dL], 108 months; TI [Hb <10 g/dL], 77 months; TD, 44 months). Transfusion dependence also negatively impacted non-leukemic death rates. In the interventional part of the study, baseline Hb levels were found to correlate significantly with physical (R = 0.666, P = 0.035) and fatigue (R = 0.604, P = 0.049) QoL scores. Median physical QoL scores improved significantly after 12 weeks' treatment with lenalidomide (+12.5; P = 0.020). Evaluable TI patients experienced early increases in Hb levels, and all attained an erythroid response. Our findings suggest that TI patients with moderate anemia may benefit from early treatment with lenalidomide. PMID- 26376971 TI - Trophodynamics of Protomyctophum (Myctophidae) in the Scotia Sea (Southern Ocean). AB - This study investigated spatial and temporal patterns in distribution, population structure and diet of Bolin's lanternfish Protomyctophum bolini, Tenison's lanternfish Protomyctophum tenisoni and gaptooth lanternfish Protomyctophum choriodon in the Scotia Sea using data collected by midwater trawl during spring, summer and autumn. Protomyctophum bolini was the most abundant species of the genus encountered throughout the Scotia Sea with the greatest concentrations occurring around the Antarctic Polar Front (APF). This species had a life cycle of 2+ years, but spatial differences in population structure were apparent as the I-group was absent from all regions south of the APF, suggesting that the species does not recruit in the Scotia Sea. Protomyctophum tenisoni occurred mostly in waters characteristic of the APF and was absent from the southern Scotia Sea. It had a limited size range, but there was clear size-related sexual dimorphism with males significantly larger than females. The species had a life cycle of c. 2 years, but the I-group (c. 1 year old, 1 November to 31 October the next year) occurred only in regions close to the APF suggesting that recruitment is restricted to these waters. A seasonal southward migration for P. choriodon is likely as the species occurred mostly to the south-west of South Georgia in summer, but extended to the sea-ice sectors in autumn. Protomyctophum choriodon had a life cycle of 4+ years in the Scotia Sea and the population was dominated by age classes >3 years old. Larval stages were absent during the surveys for all species. Diurnal variations in vertical distribution were apparent for all three species. Interspecific variations in diet were evident, but all species were primarily copepod feeders, with Metridia spp., Rhincalanus gigas and Calanus simillimus generally dominating their diet. Small euphausiids, principally Thysanoessa spp., were also an important component of their diets, particularly for P. choriodon which had the largest body size. The spatial and temporal variations in diet for both P. bolini and P. tenisoni were broadly consistent with underlying abundance patterns within the mesozooplankton community. PMID- 26376969 TI - Myasthenia gravis: subgroup classification and therapeutic strategies. AB - Myasthenia gravis is an autoimmune disease that is characterised by muscle weakness and fatigue, is B-cell mediated, and is associated with antibodies directed against the acetylcholine receptor, muscle-specific kinase (MUSK), lipoprotein-related protein 4 (LRP4), or agrin in the postsynaptic membrane at the neuromuscular junction. Patients with myasthenia gravis should be classified into subgroups to help with therapeutic decisions and prognosis. Subgroups based on serum antibodies and clinical features include early-onset, late-onset, thymoma, MUSK, LRP4, antibody-negative, and ocular forms of myasthenia gravis. Agrin-associated myasthenia gravis might emerge as a new entity. The prognosis is good with optimum symptomatic, immunosuppressive, and supportive treatment. Pyridostigmine is the preferred symptomatic treatment, and for patients who do not adequately respond to symptomatic therapy, corticosteroids, azathioprine, and thymectomy are first-line immunosuppressive treatments. Additional immunomodulatory drugs are emerging, but therapeutic decisions are hampered by the scarcity of controlled studies. Long-term drug treatment is essential for most patients and must be tailored to the particular form of myasthenia gravis. PMID- 26376970 TI - Insights from late-onset familial parkinsonism on the pathogenesis of idiopathic Parkinson's disease. AB - Disease-modifying therapies that slow or halt the progression of Parkinson's disease are an unmet clinical need. Many hypotheses have been put forward to explain the pathogenesis of the disease, but none has led to the development of disease-modifying drugs. Here we focus on familial forms of late-onset parkinsonism that most closely resemble idiopathic Parkinson's disease and present a synthesis of emerging molecular advances. Genetic discoveries and mechanistic investigations have highlighted early alterations to synaptic function, endosomal maturation, and protein sorting that might lead to an intracellular proteinopathy. We propose that these cellular processes constitute one pathway to pathogenesis and suggest that neuroprotection, as an adjunct to current symptomatic treatments, need not remain an elusive goal. PMID- 26376962 TI - Acute Tumor Lactate Perturbations as a Biomarker of Genotoxic Stress: Development of a Biochemical Model. AB - Ionizing radiation is the primary nonsurgical treatment modality for solid tumors. Its effectiveness is impacted by temporal constraints such as fractionation, hypoxia, and development of radioresistant clones. Biomarkers of acute radiation response are essential to developing more effective clinical algorithms. We hypothesized that acute perturbations in tumor lactate levels act as a surrogate marker of radiation response. In vitro experiments were carried out using validated human-derived cell lines from three histologies: anaplastic thyroid carcinoma (ATC), head and neck squamous cell carcinoma (HNSCC), and papillary thyroid carcinoma (PTC). Cellular metabolic activity was measured using standard biochemical assays. In vivo validation was performed using both an orthotopic and a flank derivative of a previously established ATC xenograft murine model. Irradiation of cells and tumors triggered a rapid, dose-dependent, transient decrease in lactate levels that was reversed by free radical scavengers. Acute lactate perturbations following irradiation could identify hypoxic conditions and correlated with hypoxia-induced radioresistance. Mutant TP53 cells and cells in which p53 activity was abrogated (shRNA) demonstrated a blunted lactate response to irradiation, consistent with a radioresistant phenotype. Lactate measurements therefore rapidly detected both induced (i.e., hypoxia) and intrinsic (i.e., mutTP53-driven) radioresistance. We conclude that lactate is a quantitative biomarker of acute genotoxic stress, with a temporal resolution that can inform clinical decision making. Combined with the spatial resolution of newly developed metabolic imaging platforms, this biomarker could lead to the development of truly individualized treatment strategies. PMID- 26376972 TI - Non-invasive determination by cardiovascular magnetic resonance of right ventricular-vascular coupling in children and adolescents with pulmonary hypertension. AB - BACKGROUND: Pediatric pulmonary hypertension (PH) remains a disease with high morbidity and mortality in children. Understanding ventricular-vascular coupling, a measure of how well matched the ventricular and vascular function are, may elucidate pathway leading to right heart failure. Ventricular vascular coupling ratio (VVCR), comprised of effective elastance (Ea, index of arterial load) and right ventricular maximal end-systolic elastance (Ees, index of contractility), is conventionally determined by catheterization. Here, we apply a non-invasive approach to determining VVCR in pediatric subjects with PH. METHODS: This retrospective study included PH subjects who had a cardiovascular magnetic resonance (CMR) study within 14 days of cardiac catheterization. PH was defined as mean pulmonary artery pressure (mPAP) >= 25 mmHg on prior or current catheterization. A non-invasive measure of VVCR was derived from CMR-only (VVCRm) and compared to VVCR estimated by catheterization-derived single beat estimation (VVCRs). Indexed pulmonary vascular resistance (PVRi) and pulmonary vascular reactivity were determined during the catheterization procedure. Pearson correlation coefficients were calculated between PVRi and VVCRm. Receiver operating characteristic (ROC) curve analysis determined the diagnostic value of VVCRm in predicting vascular reactivity. RESULTS: Seventeen subjects (3 months-23 years; mean 11.3 +/- 7.4 years) were identified between January 2009-August 2013 for inclusion with equal gender distributions. Mean mPAP was 35 mmHg +/- 15 and PVRi was 8.5 Woods unit x m2 +/- 7.8. VVCRm (range 0.43-2.82) increased with increasing severity as defined by PVRi (p < 0.001), and was highly correlated with PVRi (r = 0.92, 95 % CI 0.79-0.97, p < 0.0001). Regression of VVCRm and PVRi demonstrated differing lines when separated by reactivity. VVCRm was significantly correlated with VVCRs (r = 0.79, CI 0.48-0.99, p <0.0001). ROC curve analysis showed high accuracy of VVCRm in determining vascular reactivity (VVCR = 0.85 had a sensitivity of 100 % and a specificity of 80 %) with an area under the curve of 0.89 (p = 0.008). CONCLUSION: Measurement of VVCRm in pediatrics is feasible. Pulmonary vascular non-reactivity may be contribute to ventricular-vascular decoupling in severe PH. Therapeutic intervention to maintain a low vascular afterload in reactive patients may preserve right ventricular functional reserve and delay the onset of RV-PA decoupling. Use of VVCRm may have significant prognostic implication. PMID- 26376976 TI - KGCAK: a K-mer based database for genome-wide phylogeny and complexity evaluation. AB - BACKGROUND: The K-mer approach, treating genomic sequences as simple characters and counting the relative abundance of each string upon a fixed K, has been extensively applied to phylogeny inference for genome assembly, annotation, and comparison. RESULTS: To meet increasing demands for comparing large genome sequences and to promote the use of the K-mer approach, we develop a versatile database, KGCAK ( http://kgcak.big.ac.cn/KGCAK/ ), containing ~8,000 genomes that include genome sequences of diverse life forms (viruses, prokaryotes, protists, animals, and plants) and cellular organelles of eukaryotic lineages. It builds phylogeny based on genomic elements in an alignment-free fashion and provides in depth data processing enabling users to compare the complexity of genome sequences based on K-mer distribution. CONCLUSION: We hope that KGCAK becomes a powerful tool for exploring relationship within and among groups of species in a tree of life based on genomic data. PMID- 26376974 TI - Complete resolution of a calcifying cystic odontogenic tumor with physiological eruption of a dislocated permanent tooth after marsupialization in a child with a mixed dentition: a case report. AB - Here, we report the complete resolution of a calcifying cystic odontogenic tumor (CCOT) in the right mandible after marsupialization in an 8-year-old girl with a mixed dentition. Clinical, radiographic, and histopathological findings showed a simple cystic variant of CCOT in the region of the deciduous second molar, with dislocation of the permanent second premolar tooth germ. Initial treatment involved marsupialization, including extraction of the involved deciduous tooth, incision of pathological tissue, and creation of a window in the extraction socket. The crown of the dislocated second premolar was exposed at the base of the cystic cavity after marsupialization. One year and nine months later, complete bone healing and spontaneous eruption of the second premolar were observed, providing evidence of the bone regeneration capacity and tooth germ eruption potential in children. No recurrence was observed after 7 years. The findings from this case suggest that marsupialization can be successfully applied for the treatment of CCOT in children with a mixed dentition. PMID- 26376984 TI - [Updates from pediatric pneumology]. PMID- 26376980 TI - Open-source satellite enumeration to map households: planning and targeting indoor residual spraying for malaria. AB - BACKGROUND: Defining the number and location of sprayable structures (houses) is foundational to plan and monitor indoor residual spray (IRS) implementation, a primary intervention used to control the transmission of malaria. Only by mapping the location and type of all sprayable structures can IRS operations be planned, estimates of spray coverage determined, and targeted delivery of IRS to specific locations be achieved. Previously, field-based enumeration has been used to guide IRS campaigns, however, this approach is costly, time-consuming and difficult to scale. As a result, field-based enumeration typically fails to map all structures in a given area, making estimations less reliable and reducing the enumerated coverage. METHODS: Using open source satellite imagery and Geographic Information System software, satellite enumeration was conducted to guide IRS operations in 15 districts (91,302 km(2)) in northern Zambia during the 2014 spray season. Cost of satellite enumeration was compared to standard enumeration. Enumerated households were sampled to estimate sprayable surface area and wall type from the satellite enumeration using linear and logistic regression, respectively. RESULTS: In comparison to the traditional field-based enumeration procedure, satellite-based enumeration was 22 times faster, and 10 times less costly. An estimated 98 % of the satellite enumerated buildings correctly classified roof type. Predicted surface area of each household correlated at a value of 0.91 with measured surface area of each household. CONCLUSION: For IRS campaigns, high quality and high coverage enumeration data aid in planning, through informed insecticide procurement. Through the identification of geographical areas and populations to target, enumeration data guide operations and assist monitoring and evaluation of IRS through the unbiased estimation of coverage achieved. Satellite enumeration represents a quick, cheap and accurate system to provide these data, and has potential applications beyond IRS for delivery of other targeted or non-targeted interventions (e.g. net distributions, mass drug administration, immunization campaigns, or even sampling frames for field studies). PMID- 26376985 TI - [Der Orthopade and the impact factor]. PMID- 26376983 TI - [New international reference values for spirometry: implications for clinical issues using a comparative analysis of a paediatric population]. AB - BACKGROUND: The new lung function reference values of the global lung initiative (GLI) are recommended by most health societies. The aim of this study was to analyze FEV1- and FEV1/FVC-values from a German and Austrian patient group applying old and new reference values. RESULTS: A total of 215 Caucasian children (aged 5-17 years) were included. FEV1-values were significantly lower applying GLI reference values compared to Zapletal values (median 96.9 % pred. (87.3 105.2) versus 100.6 % pred. (quartile 91.5-111.4), p = 0.000), the median difference was 4.9 % (range -12.9 to 27.5) % pred. Differences correlated significantly with age and FEV1 in % predicted (Zapletal), p = 0.000 17/70 (24 %) patients with cystic fibrosis had FEV1-values <80% pred. applying Zapletal, in 25 (36 %) patients FEV1 was abnormal (z-score <1645) using GLI values; 3/145 asthmatics (2 %) had FEV1-Werte <80 % d.S. (Zapletal), 7/145 (5 %) z-scores <1645 (GLI). CONCLUSION: Differences between GLI-and Zapletal-reference values were considerable in pediatric asthma and CF-patients. PMID- 26376975 TI - MyD88 in lung resident cells governs airway inflammatory and pulmonary function responses to organic dust treatment. AB - Inhalation of organic dusts within agriculture environments contributes to the development and/or severity of airway diseases, including asthma and chronic bronchitis. MyD88 KO (knockout) mice are nearly completely protected against the inflammatory and bronchoconstriction effects induced by acute organic dust extract (ODE) treatments. However, the contribution of MyD88 in lung epithelial cell responses remains unclear. In the present study, we first addressed whether ODE-induced changes in epithelial cell responses were MyD88-dependent by quantitating ciliary beat frequency and cell migration following wounding by electric cell-substrate impedance sensing. We demonstrate that the normative ciliary beat slowing response to ODE is delayed in MyD88 KO tracheal epithelial cells as compared to wild type (WT) control. Similarly, the normative ODE-induced slowing of cell migration in response to wound repair was aberrant in MyD88 KO cells. Next, we created MyD88 bone marrow chimera mice to investigate the relative contribution of MyD88-dependent signaling in lung resident (predominately epithelial cells) versus hematopoietic cells. Importantly, we demonstrate that ODE-induced airway hyperresponsiveness is MyD88-dependent in lung resident cells, whereas MyD88 action in hematopoietic cells is mainly responsible for ODE-induced TNF-alpha release. MyD88 signaling in lung resident and hematopoietic cells are necessary for ODE-induced IL-6 and neutrophil chemoattractant (CXCL1 and CXCL2) release and neutrophil influx. Collectively, these findings underscore an important role for MyD88 in lung resident cells for regulating ciliary motility, wound repair and inflammatory responses to ODE, and moreover, show that airway hyperresponsiveness appears uncoupled from airway inflammatory consequences to organic dust challenge in terms of MyD88 involvement. PMID- 26376979 TI - Consumption of pharmaceutical drugs in exception region of separation for drug prescribing and dispensing program in South Korea. AB - BACKGROUND: In the year 2000, the South Korean government introduced a program for separation of drug prescribing and dispensing. The goals of the program are to reduce misuse of drugs and to contain drug expenditures. The government also designated exception regions for the program to reduce the inconvenience for people who reside in areas with a shortage of health care resources. However, according to government reports, many adverse events related to drug misuse occurred in these exception regions after the program reforms were introduced. Therefore, it is worth investigating the factors that relate to drug consumption so that misuse in exception regions can be reduced. METHODS: Data from medical institutions, detailed drug supply data, and community health survey data were included in the analysis. Multilevel linear regression analysis using mixed models that included pharmacy-and regional-level variables were used to examine the associations regarding the percentages of drug types consumed (i.e., antipyretic, analgesic, anti-inflammatory drugs, psychotropic drugs, adrenal cortical hormones, and antibiotics). RESULTS: The data used in this analysis were from a total of 16,455 pharmacies. There were 1.9 % pharmacies from program exception regions and 98.1 % pharmacies from program application regions. Compared with the pharmacies in the program application regions, the exception region pharmacies had higher values for percent consumption of the antipyretic, analgesic, anti-inflammatory drugs category, and of the adrenal cortical hormones category (antipyretic, analgesic, anti-inflammatory drugs = beta: 3.19, Standard Error (SE): 0.82, t: 3.88, p-value < 0.05; adrenal cortical hormones = beta: 0.72, SE: 0.07, t: 9.92, p-value < 0.05). CONCLUSION: Our results suggested that pharmacies in exception regions supplied more antipyretic, analgesic, anti inflammatory drugs, and more adrenal cortical hormones compared with the pharmacies where separation of drug prescribing and dispensing had been implemented. Health care professionals and health policy makers should consider management of health care expenditure by the category of drugs consumed, especially in program exception regions. PMID- 26376982 TI - Bowen's disease of the nail apparatus: a series of 8 patients and a literature review. AB - Bowen's disease of the nail apparatus is uncommon. Since often characteristic clinical features are missing, diagnosis and treatment are delayed. We have analyzed our patients' files from January 2001 to July 2015 for this disorder. We identified eight patients with Bowen's disease of the nail apparatus, six male and two female individuals. Fingers were more often affected than toes. The disease does not respect the anatomical borders of the nail apparatus. Therefore, we performed delayed Mohs surgery with skin grafts in seven patients and with second intention healing in one patient. Two relapses were noted but only one ate the same digit. Since relapses occurred after 2-3 years, a follow-up of such patients seems justified. PMID- 26376977 TI - Effects of BPA and BPS exposure limited to early embryogenesis persist to impair non-associative learning in adults. AB - BACKGROUND: Bisphenol-A (BPA) is a polymerizing agent used in plastic bottles and several routinely used consumer items. It is classified among endocrine disrupting chemicals suspected to cause adverse health effects in mammals ranging from infertility and cancer to behavioral disorders. Work with the invertebrate lab model Caenorhabditis elegans has shown that BPA affects germ cells by disrupting double-stranded DNA break repair mechanisms. The current study utilizes this model organism to provide insight into low-dose and long-term behavioral effects of BPA and bisphenol-S (BPS), a supposed safer replacement for BPA. FINDINGS: Experiments presented in our report demonstrate that the effects of embryonic exposure to considerably low levels of BPA persist into adulthood, affecting neural functionality as assayed by measuring habituation to mechano sensory stimuli in C. elegans. These results are noteworthy in that they are based on low-dose exposures, following the rationale that subtler effects that may not be morphologically apparent are likely to be discernible through behavioral changes. In addition, we report that embryonic exposure to BPS follows a pattern similar to BPA. CONCLUSIONS: Building upon previous observations using the C. elegans model, we have shown that exposure of embryos to BPA and BPS affects their behavior as adults. These long-term effects are in line with recommended alternate low-dose chemical safety testing approaches. Our observation that the effects of BPS are similar to BPA is not unexpected, considering their structural similarity. This, to our knowledge, is the first reported behavioral study on low-dose toxicity of any endocrine disrupting chemical in C. elegans. PMID- 26376986 TI - [Fusion in adolescent idiopathic scoliosis : Anterior, posterior or combined? One stage or two-stage?]. AB - Scoliosis is a complex, three-dimensional spinal deformity with various causes. Adolescent idiopathic scoliosis (AIS) is the most common form. Surgical treatment is indicated for curves greater than 45-50 degrees meaured using the Cobb method. We can distinguish among posterior, anterior or combined surgical procedures. Today, the posterior, transpedicular approach has revolutionized scoliosis surgery. This review gives an overview of current surgical options in scoliosis treatment. PMID- 26376978 TI - Fifteen-month follow up of an assertive community treatment program for chronic patients with mental illness. AB - BACKGROUND: The aim of this study was to evaluate the effect of an Assertive Community Treatment (ACT) program on psychiatric symptoms, global functioning, life satisfaction, and recovery-promoting relationships among individuals with mental illness. METHODS: Participants were patients at the Suwon Mental Health Center. Thirty-two patients were part of the ACT program and 32 patients matched for age, sex, and mental illness were in a standard case-management program and served as a control group. Follow-up with patients occurred every 3 months during the 15 months after a baseline interview. Participants completed the Brief Psychiatric Rating Scale (BPRS), Global Assessment of Functioning (GAF) Scale, Life Satisfaction Scale, and Recovery-Promoting Relationship Scale (RPRS). RESULTS: No significant differences were noted in the sociodemographic characteristics of the ACT and the case-management group. According to the BPRS, the ACT group showed a significant reduction in symptom severity, but the ACT program was not significantly more effective at reducing psychiatric symptoms from baseline to the 15-month follow-up compared to the case-management approach. The ACT group showed more significant improvement than the control group in terms of the GAF Scale. Both groups showed no significant differences in the change of life satisfaction and in the change of recovery-promoting relationships. We observed a significant increase in recovery-promoting relationships in the control group, but the degree of change of recovery-promoting relationships through time flow between groups was not significantly different. DISCUSSION: In this study, we observed that ACT was significantly better at improving the GAF than case management and that participation in ACT was associated with a significant decrease in BPRS scores. However, ACT did not demonstrate an absolute superiority over the standard case-management approach in terms of the BPRS and the measures of life satisfaction and recovery-promoting relationships. CONCLUSIONS: ACT may have some advantages over a standard case management approach. PMID- 26376981 TI - Psychiatric liaison consultations of patients without psychiatric illness in a general hospital in Germany: a retrospective analysis. AB - The aim of the study was to explore the utilization of consultation-liaison psychiatric (CLP) service among nonpsychiatric patients in a general hospital. A retrospective analysis was conducted on all patients seen by the CLP in 2013. In 66 (5.9 %) of these 1112 consultations, no psychiatric diagnosis could be identified. These cases were analyzed by department of referral, assumed psychiatric symptoms, consensus with the symptoms found by the CLP, and recommended procedures. Assumed depressive symptoms, suicidal ideations and "difficult" behavior were the predominant reasons for CLP referrals. As the results suggest, CLP service was mostly "overprovided" because of uncertainty about the working areas of psychiatrists or overestimation of the severity of symptoms. These findings emphasize the importance to develop more precise guidelines for CLP services and that it could be worth striving for a more profound psychiatric training for nonpsychiatric physicians to achieve an optimal treatment for patients. PMID- 26376987 TI - The effects of being watched on resource acquisition in chimpanzees and human children. AB - Animals react in many different ways to being watched by others. In the context of cooperation, many theories emphasize reputational effects: Individuals should cooperate more if other potential cooperators are watching. In the context of competition, individuals might want to show off their strength and prowess if other potential competitors are watching. In the current study, we observed chimpanzees and human children in three experimental conditions involving resource acquisition: Participants were either in the presence of a passive observer (observed condition), an active observer who engaged in the same task as the participant (competition condition), or in the presence of but not directly observed by a conspecific (mere presence condition). While both species worked to acquire more resources in the competition condition, children but not chimpanzees also worked to acquire more resources in the observer condition (compared to the mere presence condition). These results suggest evolutionary continuity with regard to competition-based observer effects, but an additional observer effect in young children, potentially arising from an evolutionary-based concern for cooperative reputation. PMID- 26376989 TI - Variational Characteristics and Implications of Gaseous Elemental Mercury for Three Continuous Typhoons in China. AB - Coupling air pollutants with particular meteorological conditions can induce air pollution episodes. To our knowledge, how typhoons influence mercury (Hg) as an extreme weather phenomena has not been reported. Gaseous elemental Hg (GEM) was measured during a time period (from September 16, 2011 to October 9, 2011) that included three typhoons (Haitang, Nesat, and Nalgae) at the Wuzhishan National Atmospheric Background Station. The GEM concentration during these typhoons ranged from 1.81 to 4.73 ng/m(3) (2.97 +/- 0.58 ng/m(3)), 1.27 to 4.42 ng/m(3) (2.69 +/- 0.83 ng/m(3)), and 1.43 to 2.99 ng/m(3) (2.47 +/- 0.32 ng/m(3)), which was higher than for the non-typhoon period (1.14-2.93 ng/m(3), 1.61 +/- 0.52 ng/m(3)). Simultaneously, the three typhoon periods exhibited a significant positive correlation between the GEM concentration and wind speed. These results differ from the common belief that lower pollutant concentrations will occur due to a typhoon accelerating pollutant diffusion. Changes in the wind direction and long range pollutant transport from the Chinese mainland can reasonably account for this abnormality. There was a significantly positive correlation between the GEM and SO2, NO x , CO, and O3 levels during the three typhoons periods, which indicates they came from the same sources or areas. A backward trajectory analysis and the concentration weighted field at our monitoring site indicated that clean air masses mainly came from Southeast Asia or the southeast and northeast sea surfaces during non-typhoon periods, while polluted air masses came from the Chinese mainland during the three typhoon periods. The results implied that the increased GEM concentrations in the Wuzhi Mountain were caused by the long-range atmospheric transport of Hg from the Chinese mainland during the typhoon periods. The combustion of coal may be the main emission sources. PMID- 26376973 TI - Intracellular expression of Tat alters mitochondrial functions in T cells: a potential mechanism to understand mitochondrial damage during HIV-1 replication. AB - BACKGROUND: HIV-1 replication results in mitochondrial damage that is enhanced during antiretroviral therapy (ART). The onset of HIV-1 replication is regulated by viral protein Tat, a 101-residue protein codified by two exons that elongates viral transcripts. Although the first exon of Tat (aa 1-72) forms itself an active protein, the presence of the second exon (aa 73-101) results in a more competent transcriptional protein with additional functions. RESULTS: Mitochondrial overall functions were analyzed in Jurkat cells stably expressing full-length Tat (Tat101) or one-exon Tat (Tat72). Representative results were confirmed in PBLs transiently expressing Tat101 and in HIV-infected Jurkat cells. The intracellular expression of Tat101 induced the deregulation of metabolism and cytoskeletal proteins which remodeled the function and distribution of mitochondria. Tat101 reduced the transcription of the mtDNA, resulting in low ATP production. The total amount of mitochondria increased likely to counteract their functional impairment. These effects were enhanced when Tat second exon was expressed. CONCLUSIONS: Intracellular Tat altered mtDNA transcription, mitochondrial content and distribution in CD4+ T cells. The importance of Tat second exon in non-transcriptional functions was confirmed. Tat101 may be responsible for mitochondrial dysfunctions found in HIV-1 infected patients. PMID- 26376988 TI - The polarity protein Scrib mediates epidermal development and exerts a tumor suppressive function during skin carcinogenesis. AB - BACKGROUND: The establishment and maintenance of polarity is vital for embryonic development and loss of polarity is a frequent characteristic of epithelial cancers, however the underlying molecular mechanisms remain unclear. Here, we identify a novel role for the polarity protein Scrib as a mediator of epidermal permeability barrier acquisition, skeletal morphogenesis, and as a potent tumor suppressor in cutaneous carcinogenesis. METHODS: To explore the role of Scrib during epidermal development, we compared the permeability of toluidine blue dye in wild-type, Scrib heterozygous and Scrib KO embryonic epidermis at E16.5, E17.5 and E18.5. Mouse embryos were stained with alcian blue and alizarin red for skeletal analysis. To establish whether Scrib plays a tumor suppressive role during skin tumorigenesis and/or progression, we evaluated an autochthonous mouse model of skin carcinogenesis in the context of Scrib loss. We utilised Cre-LoxP technology to conditionally deplete Scrib in adult epidermis, since Scrib KO embryos are neonatal lethal. RESULTS: We establish that Scrib perturbs keratinocyte maturation during embryonic development, causing impaired epidermal barrier formation, and that Scrib is required for skeletal morphogenesis in mice. Analysis of conditional transgenic mice deficient for Scrib specifically within the epidermis revealed no skin pathologies, indicating that Scrib is dispensable for normal adult epidermal homeostasis. Nevertheless, bi-allelic loss of Scrib significantly enhanced tumor multiplicity and progression in an autochthonous model of epidermal carcinogenesis in vivo, demonstrating Scrib is an epidermal tumor suppressor. Mechanistically, we show that apoptosis is the critical effector of Scrib tumor suppressor activity during skin carcinogenesis and provide new insight into the function of polarity proteins during DNA damage repair. CONCLUSIONS: For the first time, we provide genetic evidence of a unique link between skin carcinogenesis and loss of the epithelial polarity regulator Scrib, emphasizing that Scrib exerts a wide-spread tumor suppressive function in epithelia. PMID- 26376990 TI - Differences in Quality of Life Between Atrial Fibrillation Patients with Low Stroke Risk Treated With and Without Catheter Ablation. AB - BACKGROUND: Impacts of a single radiofrequency ablation (RFA) on quality of life (QoL) were not well investigated in atrial fibrillation (AF) patients with low stroke risk. METHODS AND RESULTS: Nine hundred AF patients with low CHADS2 score (ie, CHADS2 <=1) who completed both a baseline and 6-month Atrial Fibrillation Effect on QualiTy-of-life (AFEQT) questionnaire were selected from The Chinese Atrial Fibrillation Registry between 2011 and 2013. A final cohort of 222 patients was constructed after a propensity score matching with 74 in the RFA group and 148 in the non-RFA group. Domains of AFEQT were balanced at baseline between the 2 groups. No statistically significant differences were noted in QoL (all P>0.05) when AFEQT at 6 months was compared between groups, except for the symptoms domain (83.07+/-12.37 units in the RFA group vs. 77.68+/-17.14 units in the non-RFA group; P=0.008) and treatment satisfaction domain (76.34+/-14.92 units in the RFA group vs. 70.38+/-16.81 units in the non-RFA group; P=0.01). Within-group changes in all domains and the global score of the questionnaire were moderate to large, whereas between-group comparisons in baseline to 6-month changes and QoL at 6 months were small to moderate according to Cohen effect sizes. CONCLUSIONS: QoL was balanced at baseline and improved at 6 months in both groups from this observational propensity-matched cohort based on the AFEQT questionnaire. However, RFA treatment was only associated with small-to-moderate superiorities over non-RFA treatment. The role of RFA in QoL improvement among AF patients with low stroke risk requires further research. PMID- 26376992 TI - Impact of preoperative hemoglobin and CRP levels on cancer-specific survival in patients undergoing radical cystectomy for transitional cell carcinoma of the bladder: results of a single-center study. AB - PURPOSE: Different blood parameters have shown to be associated with patient's oncological outcome. There is only limited knowledge about the prognostic relevance of routine blood parameters in patients undergoing radical cystectomy for transitional cell carcinoma (TCC). Therefore, we retrospectively analyzed the influence of preoperative C-reactive protein (CRP) and hemoglobin (Hb) levels on overall survival (OS) and cancer-specific survival (CSS). MATERIALS AND METHODS: Preoperative CRP and Hb levels were available in 664 patients who underwent RC due to TCC from 2004 to 2013 at our institution. More men than women (77 vs. 23 %) underwent surgery with a median age of 70 years (35-97). Median follow-up time was 24 months (max. 108). Outcome was analyzed using Kaplan-Meier method, log rank test, and Cox regression models. RESULTS: Median CRP level was 0.5 mg/dl (0.1-28.3), and median Hb level was 13.4 g/dl (6.7-17.9). Patients with CRP value above the median died significantly earlier due to their disease than those with CRP below the median (median CSS 19 vs. 70 months; p < 0.001). Patients with preoperative Hb level below the median had significantly worse outcome than those with Hb level above the median (median CSS 25 vs. 78 months; p < 0.001). In multivariate analysis, CRP and Hb levels were independent prognostic parameters regarding CSS/OS (CRP p = 0.016/p = 0.004; Hb p = 0.006/p = 0.004, respectively). CONCLUSIONS: In our single-center study, preoperative CRP and Hb levels were found to be independent prognostic factors, indicating impaired outcome in patients undergoing RC for TCC. These findings could be used for individual risk stratification and optimization of therapeutic strategies. PMID- 26376991 TI - Vascular Smooth Muscle Sirtuin-1 Protects Against Aortic Dissection During Angiotensin II-Induced Hypertension. AB - BACKGROUND: Sirtuin-1 (SirT1), a nicotinamide adenine dinucleotide(+)-dependent deacetylase, is a key enzyme in the cellular response to metabolic, inflammatory, and oxidative stresses; however, the role of endogenous SirT1 in the vasculature has not been fully elucidated. Our goal was to evaluate the role of vascular smooth muscle SirT1 in the physiological response of the aortic wall to angiotensin II, a potent hypertrophic, oxidant, and inflammatory stimulus. METHODS AND RESULTS: Mice lacking SirT1 in vascular smooth muscle (ie, smooth muscle SirT1 knockout) had drastically high mortality (70%) caused by aortic dissection after angiotensin II infusion (1 mg/kg per day) but not after an equipotent dose of norepinephrine, despite comparable blood pressure increases. Smooth muscle SirT1 knockout mice did not show any abnormal aortic morphology or blood pressure compared with wild-type littermates. Nonetheless, in response to angiotensin II, aortas from smooth muscle SirT1 knockout mice had severely disorganized elastic lamellae with frequent elastin breaks, increased oxidant production, and aortic stiffness compared with angiotensin II-treated wild-type mice. Matrix metalloproteinase expression and activity were increased in the aortas of angiotensin II-treated smooth muscle SirT1 knockout mice and were prevented in mice overexpressing SirT1 in vascular smooth muscle or with use of the oxidant scavenger tempol. CONCLUSIONS: Endogenous SirT1 in aortic smooth muscle is required to maintain the structural integrity of the aortic wall in response to oxidant and inflammatory stimuli, at least in part, by suppressing oxidant-induced matrix metalloproteinase activity. SirT1 activators could potentially be a novel therapeutic approach to prevent aortic dissection and rupture in patients at risk, such as those with hypertension or genetic disorders, such as Marfan's syndrome. PMID- 26376993 TI - Imaging Surveillance of Hypervascular Liver Lesions in Non-Cirrhotic Patients. AB - A consensus surveillance protocol is lacking for non-cirrhotic patients with hypervascular liver lesions presumed to represent hepatocellular adenomas. Patients with hypervascular liver lesions <5 cm not meeting criteria for focal nodular hyperplasia or hepatocellular carcinoma underwent surveillance with contrast-enhanced magnetic resonance imaging (MRI) 6, 12, and 24 months after baseline imaging. If lesions remained stable or decreased in size, then surveillance imaging was discontinued. Between 2011 and 2014, 116 patients with hypervascular liver lesions were evaluated. Seventy-nine patients were eligible for the surveillance protocol. Median follow-up was 24 months (range, 1-144 months). One patient (1 %) continued oral contraceptive pill (OCP) use and presented with hemorrhage requiring embolization 5 months after initial diagnosis. Ten patients (13 %) underwent elective embolization or surgical resection for size >=5 cm. The remaining 68 patients (86 %) continued surveillance without hemorrhage or malignant transformation. Risk factors for requiring intervention during the surveillance period included younger age, larger lesion size, and estrogen use (all p < 0.05). Patients with hepatocellular adenomas <5 cm can safely be observed after discontinuing OCP with serial imaging 6, 12, and 24 months after diagnosis. If lesions remain stable or decrease in size, then longer-term surveillance is unlikely to identify patients at risk for complications. PMID- 26376994 TI - Role of Adjuvant Radiotherapy in Left-Sided Pancreatic Cancer-Population-Based Analysis with Propensity Score Matching. AB - This population-based study evaluated the survival impact of postoperative radiotherapy (PORT) in left-sided pancreatic cancer. The Surveillance, Epidemiology, and End Results (SEER) database was used to identify patients with surgically resected left-sided pancreatic adenocarcinoma from 2004 to 2010. Propensity score matching was conducted to compare PORT and non-PORT groups. A total of 445 patients were identified, and PORT was performed in 180 (40 %) patients. In the unmatched population, there were no significant differences in overall survival (OS) (P = 0.197) and cause-specific survival (CSS) (P = 0.379) between the PORT and non-PORT groups. After propensity score matching, the patients treated with PORT had longer median OS (P = 0.012) and CSS (P = 0.039) than the non-PORT group. In propensity-adjusted multivariate analysis, non receipt of PORT was a poor prognostic factor in OS (hazard ratio [HR] 1.39, 95 % confidence interval [CI] 1.08-1.79), and CSS (HR 1.31, 95 % CI 1.01-1.71). The log odds of positive lymph nodes (LOODS) (>=-0.73) was also associated with worse OS (P = 0.003) and CSS (P = 0.001). In left-sided pancreatic cancer, considering the addition of PORT is a reasonable option as in pancreatic head cancer. The LOODS was suggested as a strong predictive indicator of the patients' prognoses. PMID- 26376995 TI - A comparative study of prevalence-based incidence estimation techniques with application to dementia data in Germany. AB - Dementia is becoming a major health burden, which is mainly due to the increasing life expectancy in many developed countries. To describe the disease progression of individuals, multistate models are generally appropriate tools. These models allow the individuals to move along a path consisting of a finite number of disease states. We consider a simplifying illness-death model in which the subjects progress through the states healthy, diseased and dead. We use this model to study analytic relationships between the prevalence, incidence and mortality rates of irreversible diseases that have been applied in the past. One of these approaches is a rather recently proposed technique based on an ordinary differential equation (ODE). We conduct a simulation study to compare the performance of two suggested numerical approximations of this ODE with three alternative techniques, the common goal of which is to estimate age-specific incidence from cross-sectional information. The quality of the estimation methods is further explored using data on dementia in Germany. In the simulation scenarios as well as in the dementia data setting, the ODE method turns out to be the predominant technique with regard to the quality of the estimation of the known incidence regimes. PMID- 26376996 TI - Jane Dacre: Heavily indebted to Barty. PMID- 26376997 TI - Considerations on self-psychology and eating disorders. AB - In this narrative review article, some considerations are reported on the psychoanalytic point of view of self-psychology on eating disorders in a multidisciplinary team approach, a theoretic and clinical perspective in which the Author recognizes himself. Some author's clinical ideas and concepts as "negative self", "eclipse of the self", "rebound syndrome", "bluff syndrome", "deficit of subjective attribution", related to the topic of the deficit of the Self, are exposed along with technical aspects, clinical material and references to the comparison of psychoanalysis with the EBM literature on psychotherapy of EDs and its contemporary role in an integrated multi-disciplinary treatment of these disorders. PMID- 26376998 TI - Inhibition of microRNA-196a might reverse cisplatin resistance of A549/DDP non small-cell lung cancer cell line. AB - We aimed to explore the possible mechanism of microRNA-196a (miR-196a) inhibition and reversion of drug resistance to cisplatin (DDP) of the A549/DDP non-small cell lung cancer (NSCLC) cell line. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect expression differences of miR-196a in the drug-resistant A549/DDP NLCLC cell line and the parental A549 cell line, and expressions of miR-196a in the A549/DDP NLCLC cell line transfected with miR-196a inhibitor (anti-miR-196a group) and the miR-196a negative control (miR-NC) group and blank group (without transfection). 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) test was applied in examining the cell viability of A549/DDP cell line before and after transfection. Clonogenic assay was used to detect cell proliferation ability. Flow cytometry was applied in detecting apoptosis rate of assayed tumor cell and rhodamine-123 changes in cells. Western blot was applied in detecting proteins of drug-resistant related gene in A549/DDP cell line. Significantly higher expression of miR-196a was detected in the drug-resistant A549/DDP cell line than that in the parental A549 cell line (P < 0.05). However, miR-196a expression in the anti-miR-196a group decreased obviously compared to that in the blank group and the miR-NC group (both P < 0.05); The value of IC50 in the anti-miR-196a group showed remarkably lower than that in the blank group and the miR-NC group (both P < 0.05); Rh-123 absorbing ability in the anti-miR-196a group increased 2.51 times and 2.49 times respectively compared to that in the blank group and the miR-NC group (both P < 0.05). No statistical differences in the apoptosis rate of A549/DDP cell line in the early stage were found among the three groups (all P > 0.05), but the late stage apoptosis rate in the anti-miR-196a group was significantly higher than that in the blank group and the miR-NC group (both P < 0.05); The expressions of human multidrug resistance 1 (MDR1), multidrug resistance protein 1 (MRP1), excision repair cross-complementation 1 (ERCC1), survivin, and B cell lymphoma 2 (Bcl-2) decreased significantly while RhoE increased significantly in the anti miR-196a group than the blank group and the miR-NC group (all P < 0.05). Inhibition of miR-196a could reverse cisplatin resistance of A549/DDP cell lines, which might relate with inhibition of drug efflux, down-regulation of drug resistant protein expression, cell apoptosis, and cell proliferation suppression. PMID- 26376999 TI - An orally administered DNA vaccine targeting vascular endothelial growth factor receptor-3 inhibits lung carcinoma growth. AB - Lung cancer is the leading cause of mortality and 5-year survival rate is very low worldwide. Recent studies show that vascular endothelial growth factor receptor-3 (VEGFR-3) signaling pathway contributes to lung cancer progression. So we hypothesize that an oral DNA vaccine that targets VEGFR-3 carried by attenuated Salmonella enterica serovar typhimurium strain SL3261 has impacts on lung cancer progression. In this study, the oral VEGFR-3-based vaccine-immunized mice showed appreciable inhibition of tumor growth and tumor lymphatic microvessels in lung cancer mice model. Moreover, the oral VEGFR-3-based vaccine immunized mice showed remarkable increases in both VEGFR-3-specific antibody levels and cytotoxic activity. Furthermore, the oral VEGFR-3-based vaccine immunized mice showed a significant increase in the levels of T helper type 1 (Th1) cell intracellular cytokine expression (IL-2, IFN-gamma, and TNF-alpha). After inoculation with murine Lewis lung carcinoma (LLC) cells, CD4(+) or CD8(+) T cell numbers obviously declined in control groups whereas high levels were maintained in the oral VEGFR-3-based vaccine group. These results demonstrated that the oral VEGFR-3-based vaccine could induce specific humoral and cellular immune responses and then significantly inhibit lung carcinoma growth via suppressing lymphangiogenesis. PMID- 26377001 TI - The role of participation sampling and statistical analysis in medical research. PMID- 26377000 TI - The relationship of recombination rate, genome structure, and patterns of molecular evolution across angiosperms. AB - BACKGROUND: Although homologous recombination affects the efficacy of selection in populations, the pattern of recombination rate evolution and its effects on genome evolution across plants are largely unknown. Recombination can reduce genome size by enabling the removal of LTR retrotransposons, alter codon usage by GC biased gene conversion, contribute to complex histories of gene duplication and loss through tandem duplication, and enhance purifying selection on genes. Therefore, variation in recombination rate across species may explain some of the variation in genomic architecture as well as rates of molecular evolution. We used phylogenetic comparative methods to investigate the evolution of global meiotic recombination rate in angiosperms and its effects on genome architecture and selection at the molecular level using genetic maps and genome sequences from thirty angiosperm species. RESULTS: Recombination rate is negatively correlated with genome size, which is likely caused by the removal of LTR retrotransposons. After correcting recombination rates for euchromatin content, we also found an association between global recombination rate and average gene family size. This suggests a role for recombination in the preservation of duplicate genes or expansion of gene families. An analysis of the correlation between the ratio of nonsynonymous to synonymous substitution rates (dN/dS) and recombination rate in 3748 genes indicates that higher recombination rates are associated with an increased efficacy of purifying selection, suggesting that global recombination rates affect variation in rates of molecular evolution across distantly related angiosperm species, not just between populations. We also identified shifts in dN/dS for recombination proteins that are associated with shifts in global recombination rate across our sample of angiosperms. CONCLUSIONS: Although our analyses only reveal correlations, not mechanisms, and do not include potential covariates of recombination rate, like effective population size, they suggest that global recombination rates may play an important role in shaping the macroevolutionary patterns of gene and genome evolution in plants. Interspecific recombination rate variation is tightly correlated with genome size as well as variation in overall LTR retrotransposon abundances. Recombination may shape gene to-gene variation in dN/dS between species, which might impact the overall gene duplication and loss rates. PMID- 26377002 TI - Reply to letter: The role of participation sampling and statistical analysis in medical research. PMID- 26377003 TI - Complementary activation of the ipsilateral primary motor cortex during a sustained handgrip task. AB - PURPOSE: Near-infrared spectroscopy (NIRS) can be used to examine bilateral motor cortex activation during a sustained motor task in brain areas where increased oxygenation reflects cortical activation. This study examines the time course of activation of the bilateral motor cortex during a moderate-intensity handgrip task. METHODS: Ten healthy right-handed male subjects participated in this study. Functional NIRS probes were placed over the cortex to measure motor cortical activations while the subjects performed a 180-s handgrip task incrementally [30 60% of the maximal voluntary contraction (MVC) at 0.17% increase/s] RESULTS: Contralateral primary motor cortex (ContraM1) oxygenation values significantly increased from baseline between 40 and 120 s after the start of the motor task (p < 0.05). Moreover, the ipsilateral primary motor cortex (IpsiM1) oxygenation values significantly increased from baseline between 140 and 180 s after the start of the motor task (p < 0.05). IpsiM1 oxygenation gradually increased from 140 to 180 s, whereas ContraM1 oxygenation gradually decreased from 120 to 180 s after the start of the motor task. CONCLUSION: These results suggest that the complementary functions of IpsiM1 become activated in response to the working of the ContraM1 during a continuous handgrip task. PMID- 26377005 TI - Metabolic chemotypes of CITES protected Dalbergia timbers from Africa, Madagascar, and Asia. AB - RATIONALE: The genus Dalbergia includes approximately 250 species worldwide. Of these, 58 species are of economic importance and listed under CITES. Identification of illegal transnational timber trade is a challenge because logs or boards lack the typical descriptors used for species identification such as leaves and flowers; therefore, frequently the lowest taxonomic determination of these tree byproducts is genus. In this study, we explore the use of Direct Analysis in Real Time (DART) Time-Of-Flight Mass Spectrometry (TOFMS) in making species determinations of protected Dalbergia trees from Africa, Madagascar, and Asia. METHODS: Metabolic profiles were collected using DART TOFMS from the heartwood of seven species and the sapwood of 17 species of Dalbergia. Also included in this study are 85 Dalbergia heartwood samples from Madagascar that were only identified to genus. In all, 21 species comprising 235 specimens were analyzed, the metabolic chemotypes were interpreted, and the spectra were analyzed using chemometric tools. RESULTS: Dalbergia cochinchinensis and Dalbergia spp. from Madagascar (both CITES Appendix II) could be differentiated from each other and from the non-protected Dalbergia latifolia and Dalbergia melanoxylon. CONCLUSIONS: DART TOFMS is a valuable high-throughput tool useful for making phytochemical classifications of Dalbergia spp. The data produced allows the protected Dalbergias from Madagascar to be distinguished and can differentiate closely related rosewood trees. PMID- 26377004 TI - Muscle damage, inflammatory, immune and performance responses to three football games in 1 week in competitive male players. AB - PURPOSE: We examined effects of a three-game, 1-week microcycle (G1, G2, G3) on recovery of performance and inflammatory responses in professional male footballers. METHODS: Players were randomized into an experimental (EXP; N = 20) and a control group (CON; N = 20). Blood was drawn and repeated sprint ability (RSA), muscle soreness and knee range of motion (KJRM) were determined pre- and post-games and during recovery. RESULTS: High-intensity running during G2 was 7 14% less compared to G1 and G3. RSA declined in EXP by 2-9% 3 days post-game with G2 causing the greatest performance impairment. In EXP, game play increased muscle soreness (~sevenfold) compared to CON with G2 inducing the greatest rise, while KJRM was attenuated post-game in EXP compared to CON (5-7%) and recovered slower post G2 and G3 than G1. CK, CRP, sVCAM-1, sP-Selectin and cortisol peaked 48 h post-games with G2 eliciting the greatest increase. Leukocyte count, testosterone, IL-1beta and IL6 responses, although altered 24 h post each game, were comparable among games. Plasma TBARS and protein carbonyls rose by ~50% post games with G2 eliciting the greatest increase 48 h of recovery. Reduced to oxidized glutathione ratio declined for 24 h post all games with G2 displaying the slowest recovery. Total antioxidant capacity and glutathione peroxidase activity increased (9-56%) for 48 h in response to game play. CONCLUSION: In summary, post-game performance recovery and inflammatory adaptations in response to a three-game weekly microcycle displayed a different response pattern, with strong indications of a largest physiological stress and fatigue after the middle game that was preceded by only a 3-day recovery. PMID- 26377006 TI - Application of chemometrics to resolve overlapping mass spectral peak clusters between trichloroethylene and its deuterated internal standard. AB - RATIONALE: Using one or two (2) H-atom-labeled analogs as internal standards (ISs) may cause a 'cross-contribution' problem (i.e., the overlap of ions from the IS and the analyte) especially for halogenated volatile organic compounds (VOCs). However, in this situation the overlapping peak clusters of the analyte and ISs can be resolved by multivariate chemometric methods such as classical least-squares (CLS) and inverse least-squares (ILS). METHODS: Trichloroethylene (TCE) and its internal standard, deuterated TCE (TCE-d), as model compounds, were analyzed using portable gas chromatography/mass spectrometry. CLS and ILS were applied to resolve overlapping TCE and TCE-d mass spectral signals and evaluated for the determination of TCE. CLS and ILS models were constructed and used to predict concentration ratios of TCE to TCE-d. Calibration samples were prepared by adding TCE at different concentrations and TCE-d at 300 ng mL(-1) as an IS. RESULTS: The calibration curve was linear over a range of 10-1000 ng mL(-1) with a coefficient of determination (R(2)) of 0.993. A validation data set collected 2 weeks later was used to further test the model robustness. Lower prediction errors and higher correlation coefficients were obtained from TCE/TCE-d ratios predicted by the CLS model. CONCLUSIONS: This paper describes the first application of CLS to deconvolute overlapping peaks between an analyte and its corresponding isotopic internal standard for quantification. The proposed method enables simple isotopic analogs of analytes (one H or C atom is isotopically labeled) to be used as internal standards for analytes with isotopic distributions. It has wide application because of the environmental impact and prevalence of halogenated VOCs, especially when analytes have isotopic distributions that overlap with an internal standard or when sophisticated isotopic analogs of the analytes with three or more (2)H- or/and (13)C-atoms are prohibitively expensive or even impossible. PMID- 26377007 TI - Systematic evaluation of label-free and super-SILAC quantification for proteome expression analysis. AB - RATIONALE: Advanced implementations of mass spectrometry (MS)-based proteomics allow for comprehensive proteome expression profiling across many biological samples. The outcome of such studies critically depends on accurate and precise quantification, which has to be ensured for high-coverage proteome analysis possible on fast and sensitive mass spectrometers such as quadrupole orbitrap instruments. METHODS: We conducted ultra-high-performance liquid chromatography (UHPLC)/MS experiments on a Q Exactive to systematically compare label-free proteome quantification across six human cancer cell lines with quantification against a shared reference mix generated by stable isotope labeling with amino acids in cell culture (super-SILAC). RESULTS: Single-shot experiments identified on average about 5000 proteins in the label-free compared to about 3500 in super SILAC experiments. Label-free quantification was slightly less precise than super SILAC in replicate measurements, verifying previous results obtained for lower proteome coverage. Due to the higher number of quantified proteins, more significant differences were detected in label-free cell line comparisons, whereas a higher percentage of quantified proteins was identified as differentially expressed in super-SILAC experiments. Additional label-free replicate analyses effectively compensated for lower precision of quantification. Finally, peptide fractionation by high pH reversed-phase chromatography prior to LC/MS analysis further increased the robustness and precision of label-free quantification in conjunction with higher proteome coverage. CONCLUSIONS: Our results benchmark and highlight the utility of label-free proteome quantification for applications such as target and biomarker discovery on state-of-the-art UHPLC/MS workflows. PMID- 26377008 TI - Tandem mass spectrometry and density functional theory of RDX fragmentation pathways: Role of ion-molecule complexes in loss of NO3 and lack of molecular ion peak. AB - RATIONALE: Hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) is an explosive compound that finds a wide range of military and civilian applications. RDX has been a target in environmental matrices by gas chromatography/tandem mass spectrometry (GC/MS/MS). MS/MS in negative chemical ionization (NCI) mode of RDX provides important fragmentation patterns that are useful for structural elucidation. The fragmentation patterns are needed for proper identification of precursor and product ions in analytical methods that depend on MS/MS approaches for a reliable identification of RDX. METHODS: This study focuses on the MS fragmentation mechanisms of RDX in NCI mode using both MS/MS and density functional theory (DFT). The DFT studies were performed at the B3LYP/6-311G(d,p) level of theory. RESULTS: The DFT results showed that NCI of RDX leads to the formation of an anion-molecule complex that was energetically more stable than the RDX anion. The fragmentation proceeds through two pathways, leading to the loss of NO(2) and NO(3). The loss of NO(3) takes place in an anion-molecule complex leading to the formation of characteristic nitroso group fragment ions. Using the fragmentation schemes, important ion structures are proposed including structures for m/z 160, 129, 102, and 86. CONCLUSIONS: The results demonstrate the importance of both charge-induced and charge-remote dissociations in RDX pathways. The ion structures identified along the pathways could be used as targets in analytical methods for reliable identification purposes. PMID- 26377009 TI - Matrix-assisted laser desorption/ionization time-of-flight vs. fast-atom bombardment and electrospray ionization mass spectrometry in the structural characterization of bacterial poly(3-hydroxyalkanoates). AB - RATIONALE: Bacterial poly(3-hydroxyalkanoates) (PHAs) are an emergent class of plastic materials available from renewable resources. Their properties are strictly correlated with the comonomeric composition and sequence, which may be determined by various mass spectrometry approaches. In this paper we compare fast atom bombardment (FAB) and electrospray ionization (ESI) to matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) of partially pyrolyzed samples. METHODS: We determined the compositions and sequences of the medium-chain-length PHAs (mcl-PHAs) prepared by bacterial fermentation of Pseudomonas aeruginosa ATCC 27853 cultured in media containing fatty acids with 8, 12, 14, 18, and 20 carbon atoms as carbon sources by means of MALDI-TOFMS of pyrolyzates, and compared the results with those obtained by FAB- and ESI-MS in previous studies. MALDI matrices used were 9-aminoacridine (9-AA) and indoleacrylic acid (IAA). RESULTS: MALDI-TOFMS was carried out in negative ion mode when using 9-AA as a matrix, giving a semi-quantitative estimation of the 3 hydroxyacids constituting the PHAs, and in positive mode when using IAA, allowing us, through statistical analysis of the relative intensity of the oligomers generated by pyrolysis, to establish that the polymers obtained are true random copolyesters and not a mixture of homopolymers or copolymers. CONCLUSIONS: MALDI TOFMS in 9-AA and IAA of partial pyrolyzates of mcl-PHAs represents a powerful method for the structural analysis of these materials. In comparison with FAB and ESI, MALDI provided an extended mass range with better sensitivity at higher mass and a faster method of analysis. PMID- 26377010 TI - Population and individual foraging patterns of two hammerhead sharks using carbon and nitrogen stable isotopes. AB - RATIONALE: Individual foraging behavior is an important variable of predators commonly studied at the population level. Some hammerhead shark species play a significant role in the marine ecosystem as top consumers. In this context, stable isotope analysis allows us to infer some ecological metrics and patterns that cannot usually be obtained using traditional methods. METHODS: We determined the isotopic composition (delta(13)C and delta(15)N values) of dorsal muscle and vertebrae of Sphyrna lewini and Sphyrna zygaena using a continuous-flow system consisting of an elemental analyzer combined with a Delta Plus XL mass spectrometer. Foraging variability by sex and by individual was inferred from the isotopic values. RESULTS: There were no significant differences in the isotopic values of muscle samples between sexes, but there were differences between species. The trophic niche breadth of the two species was similar and overlap was low. A low niche overlap was observed between S. lewini individual vertebrae. We found differences in the delta(15)N values of S. zygaena vertebrae, with lower values in the first group of samples. CONCLUSIONS: Despite these hammerhead shark species inhabiting the same area, there was low trophic niche overlap between species and individuals, due to different individual foraging strategies, according to the carbon and nitrogen isotopic profiles obtained. The use of tissues that retain lifetime isotopic information is useful to complement studies on trophic ecology. PMID- 26377011 TI - The impact of carbon-13 and deuterium on relative quantification of proteins using stable isotope diethyl labeling. AB - RATIONALE: Stable isotopic labeling techniques are useful for quantitative proteomics. A cost-effective and convenient method for diethylation by reductive amination was established. The impact using either carbon-13 or deuterium on quantification accuracy and precision was investigated using diethylation. METHODS: We established an effective approach for stable isotope labeling by diethylation of amino groups of peptides. The approach was validated using matrix assisted laser desorption/ionization time-of-flight (MALDI-TOF) and nanospray liquid chromatography/electrospray ionization (nanoLC/ESI)-ion trap/orbitrap for mass spectrometric analysis as well as MaxQuant for quantitative data analysis. RESULTS: Reaction conditions with low reagent costs, high yields and minor side reactions were established for diethylation. Furthermore, we showed that diethylation can be applied to up to sixplex labeling. For duplex experiments, we compared diethylation in the analysis of the proteome of HeLa cells using acetaldehyde-(13) C(2)/(12) C(2) and acetaldehyde-(2) H(4)/(1) H(4). Equal numbers of proteins could be identified and quantified; however, (13) C(4)/(12) C(4) -diethylation revealed a lower variance of quantitative peptide ratios within proteins resulting in a higher precision of quantified proteins and less falsely regulated proteins. The results were compared with dimethylation showing minor effects because of the lower number of deuteriums. CONCLUSIONS: The described approach for diethylation of primary amines is a cost-effective and accurate method for up to sixplex relative quantification of proteomes. (13) C(4)/(12) C(4) -diethylation enables duplex quantification based on chemical labeling without using deuterium which reduces identification of false-negatives and increases the quality of the quantification results. PMID- 26377012 TI - Identification of alkaloid constituents from Fangchi species using pH control liquid-liquid extraction and liquid chromatography coupled to quadrupole time-of flight mass spectrometry. AB - RATIONALE: Fangchi (F.) species from four different origins have been widely used to treat or prevent diseases, and their main constitutes are several types of alkaloids. Identification of alkaloids in F. species is a necessary step to understand the therapeutic properties of each different origin, but this has not yet been fully performed. METHODS: Several types of alkaloids were extracted from F. species using ultrasonication with 70% CH(3)OH and the extract was partitioned at pH 2 and 12 to enrich alkaloid constituents and to remove interferences. The separation of alkaloids in the Fangchi extract was performed on a C18 column using gradient elution and their tandem mass spectra were obtained by quadrupole time-of-flight tandem mass spectrometry (QTOF-MS/MS) to perform accurate mass measurements of fragment ions for the alkaloid constituents. RESULTS: Several types of alkaloids were successfully separated and identified by LC/ESI-MS/MS. The structural assignment of individual alkaloids was performed based on convergence of MS/MS spectral data, pH partitioning behavior, LC retention behavior, and accurate mass measurements. The pH partition of the extract provided structural information about unknown alkaloids extracted from Fangchi species. A total of 28 compounds were identified and tentatively characterized, and of these 10 alkaloids were reported for the first time in the investigated F. species. CONCLUSIONS: The chemical profiling of alkaloids in F. species with different origins was performed for the first time and provided diagnostic ions for diverse alkaloids in F. species. Marker compounds were suggested based on the 28 characterized compounds for quality evaluation and the differentiation of Fangchi species with four different origins. PMID- 26377013 TI - Variation in delta15 N and delta13 C stable isotope values in common dolphins (Delphinus spp.) worldwide, with particular emphasis on the eastern North Atlantic populations. AB - RATIONALE: Distinguishing population units of small cetaceans continuously distributed in a widespread area is challenging but critical for their conservation and management. The use of chemical markers allows the investigation of foraging ecology and inter-specific variability, in order to detect population structure and niche segregation in the common dolphin (Delphinus spp.). METHODS: The stable isotope ratios of carbon (delta(13)C values) and nitrogen (delta(15)N values) were measured in the bone tissue of common dolphins accidentally by caught or stranded along the north-eastern and eastern Subtropical Atlantic Ocean, by means of continuous flow elemental analyser/isotope ratio mass spectrometry. Trophic positions were determined and compared, taking into account the local ecosystem trophic baseline for each study area. Data obtained for the study areas were qualitatively compared with those for common dolphin species/populations distributed worldwide. RESULTS: The delta(13)C and delta(15)N values were higher in the eastern Subtropical Atlantic as a consequence of the coexistence in the area of the common dolphin short- and long-beaked morphotypes. Individuals from the north-eastern Atlantic displayed lower delta(15)N values, reflecting dissimilarities in diet and variation in local isotopic baselines. Comparisons with other areas around the world suggest that the species is extremely adaptive and feeds at different trophic levels to adapt to local variations. CONCLUSIONS: Stable isotopes are a useful tool to investigate population structure and trophic niche segregation. The trophic behaviour of worldwide populations of common dolphins was fruitfully analysed and revealed substantial differences, probably reflective of both adaptive strategies of the genus and dissimilarities in the structure of the ecosystems. PMID- 26377014 TI - Gas-phase Smiles rearrangement reactions of deprotonated N-phenylbenzamides studied by electrospray ionization tandem mass spectrometry. AB - RATIONALE: Electrospray ionization tandem mass spectrometry (ESI-MS(n)) is an invaluable tool for the study of gas-phase reactions. When N-phenylbenzamide is analyzed in negative ion mode, the nucleophilic deprotonated site of nitrogen or oxygen, together with the adjacent electrophilic phenyl carbon in the same molecule, provides a useful opportunity to study the intramolecular nucleophilic reaction in the gas phase. METHODS: All MS(n) experiments of deprotonated N phenylbenzamides were conducted on an ion trap mass spectrometer using ESI in negative ion mode. The accurate masses of fragments were measured on an ESI quadrupole time-of-flight mass spectrometer in negative ion mode. Theoretical calculations were conducted at the B3LYP/6-31++G(d,p) level of density functional theory using the Gaussian 03 program. RESULTS: When the polarity of the substituent on the aniline ring was changed, gas-phase Smiles rearrangement reactions could be initiated by different atoms in the anionic center. Upon collisional activation, loss of CO from deprotonated N-phenylbenzamides could be observed, which can be interpreted as a nitrogen anion triggering the Smiles rearrangement reaction through a three-membered ring transition state. As the aniline ring was substituted by a strong electron-withdrawing group (e.g., NO(2), COCH(3), or CF(3)) at the para position, a characteristic phenolate anion was obtained, which was derived from the Smiles rearrangement reaction initiated by the oxygen anion through a four-membered ring transition state. CONCLUSIONS: In the fragmentation of deprotonated N-phenylbenzamides, the gas-phase Smiles rearrangement reaction initiated by either the nitrogen or the oxygen atom can proceed. The findings in this study have not only enriched knowledge on the gas phase Smiles rearrangement reactions, but also provided valuable information for understanding the rearrangements of deprotonated aromatic amides in gas phase. PMID- 26377015 TI - Mass spectral studies on 1-n-pentyl-3-(1-naphthoyl)indole (JWH-018), three deuterium-labeled analogues and the inverse isomer 1-naphthoyl-3-n-pentylindole. AB - RATIONALE: A number of synthetic cannabinoids such as the 1-alkyl-3-acylindoles are the target of significant designer drug activity. One of the first waves of these compounds identified in clandestine samples was 1-n-pentyl-3-(1 naphthoyl)indole, JWH-018. These totally synthetic molecules can be prepared in a number of regioisomeric forms. METHODS: The electron ionization mass spectrometric (EI-MS) fragmentation of the 1-n-pentyl-3-(1-naphthoyl)indole is compared to its inverse isomer 1-naphthoyl-3-n-pentylindole. These two substances are directly available from indole using identical precursor reagents and similar reaction conditions. Stable isotope deuterium labeling of the three major regions of the JWH-018 molecule allows confirmation of the structures of the major fragment ions. The spectra for the 1-n-pentyl-3-(1-naphthoyl)-d(5) -indole, 1-n pentyl-3-(1-d(7) -naphthoyl)indole and 1-d(11) -n-pentyl-3-(1-naphthoyl)indole provide significant assistance in elucidating the structures for the major fragment ions in JWH-018. RESULTS: The EI mass spectra for these isomers show a number of unique ions which allow for the differentiation of the 1-alkyl-3 acylindole compounds from the inverse regioisomeric 1-acyl-3-alkylindoles. The fragment ion [M-17](+) at m/z 324 for JWH-018 was formed by the elimination of a hydroxyl radical and the spectra of the three deuterium-labeled derivatives indicated the loss of hydrogen from the naphthalene ring. Further structural analogues suggest the hydrogen to come from the 8-position of the naphthalene ring. CONCLUSIONS: The three deuterium-labeled analogues provide significant assistance in confirming the structures for the major fragment ions in the mass spectrum of the traditional synthetic cannabinoid compound, 1-n-pentyl-3-(1 naphthoyl)indole, JWH-018. The 1-naphthoyl-3-n-pentylindole inverse regioisomer can be easily differentiated from the traditional synthetic cannabinoid compound. PMID- 26377016 TI - Isotopic disproportionation during hydrogen isotopic analysis of nitrogen-bearing organic compounds. AB - RATIONALE: High-precision hydrogen isotope ratio analysis of nitrogen-bearing organic materials using high-temperature conversion (HTC) techniques has proven troublesome in the past. Formation of reaction products other than molecular hydrogen (H(2)) has been suspected as a possible cause of incomplete H(2) yield and hydrogen isotopic fractionation. METHODS: The classical HTC reactor setup and a modified version including elemental chromium, both operated at temperatures in excess of 1400 degrees C, have been compared using a selection of nitrogen bearing organic compounds, including caffeine. A focus of the experiments was to avoid or suppress hydrogen cyanide (HCN) formation and to reach quantitative H(2) yields. The technique also was optimized to provide acceptable sample throughput. RESULTS: The classical HTC reaction of a number of selected compounds exhibited H(2) yields from 60 to 90 %. Yields close to 100 % were measured for the experiments with the chromium-enhanced reactor. The delta(2)H values also were substantially different between the two types of experiments. For the majority of the compounds studied, a highly significant relationship was observed between the amount of missing H(2) and the number of nitrogen atoms in the molecules, suggesting the pyrolytic formation of HCN as a byproduct. A similar linear relationship was found between the amount of missing H(2) and the observed hydrogen isotopic result, reflecting isotopic fractionation. CONCLUSIONS: The classical HTC technique to produce H(2) from organic materials using high temperatures in the presence of glassy carbon is not suitable for nitrogen bearing compounds. Adding chromium to the reaction zone improves the yield to 100 % in most cases. The initial formation of HCN is accompanied by a strong hydrogen isotope effect, with the observed hydrogen isotope results on H(2) being substantially shifted to more negative delta(2)H values. The reaction can be understood as an initial disproportionation leading to H(2) and HCN with the HCN hydrogen systematically enriched in (2)H by more than 50 0/00. In the reaction of HCN with chromium, H(2) and chromium-containing solid residues are formed quantitatively. PMID- 26377017 TI - Fragmentation patterns of boron-dipyrromethene (BODIPY) dyes by electrospray ionization high-resolution tandem mass spectrometry. AB - RATIONALE: 4,4-Difluoro-4-bora-3a,4a-diaza-s-indacene derivatives (BODIPYs) are fluorescent organic dyes that are widely used as non-radioactive labels in biological analyses. The fragmentation behaviour of ten structurally related BODIPYs was studied using tandem mass spectrometry (MS/MS), to support the structural elucidation process during synthesis. METHODS: The BODIPYs were investigated by electrospray ionization (ESI)-MS/MS, utilizing collision-induced dissociation (CID) data from triple quadrupole MS and high-resolution, accurate mass CID data from Fourier transform ion cyclotron resonance (FTICR) experiments. RESULTS: Unusual radical molecular cations ([M](+*)) were formed directly during the ESI process. These radical species dissociated into a large range of product ions during the subsequent CID experiments. Superimposed dissociations originating from parallel [M](+*) and [M+H](+) decompositions significantly complicated the interpretation of the MS/MS spectra. CONCLUSIONS: Detailed dissociation mechanisms were proposed in this study for BODIPY dyes. The elemental formulae of CID product ions were unambiguously assigned using FTICR-MS and unique fragment ions were discovered for the rapid identification of methyl, ethyl, butyl, tert-butyl, and phenyl substituents of individual dyes in BODIPY synthesis mixtures by low-resolution MS. PMID- 26377018 TI - Rainwater, soil water, and soil nitrate effects on oxygen isotope ratios of nitrous oxide produced in a green tea (Camellia sinensis) field in Japan. AB - RATIONALE: The oxygen exchange fraction between soil H(2)O and N(2)O precursors differs in soils depending on the responsible N(2)O-producing process: nitrification or denitrification. This study investigated the O-exchange between soil H(2)O and N(2)O precursors in a green tea field with high N(2)O emissions. METHODS: The rainwater delta(18)O value was measured using cavity ring-down spectrometry (CRDS) and compared with that of soil water collected under the tea plant canopy and between tea plant rows. The intramolecular (15)N site preference in (beta) N(alpha) NO (SP = delta(15)N(alpha) - delta(15)N(beta)) was determined after measuring the delta(15)N(alpha) and delta(15)N(bulk) values using gas chromatography/isotope ratio mass spectrometry (GC/IRMS), and the delta(18) O values of N(2)O and NO(3)(-) were also measured using GC/IRMS. RESULTS: The range of delta(18)O values of rainwater (-11.150/00 to -4.910/00) was wider than that of soil water (-7.940/00 to -5.640/00). The delta(18)O value of soil water at 50 cm depth was not immediately affected by rainwater. At 10 cm and 20 cm depths of soil between tea plant rows, linear regression analyses of delta(18)O-N(2)O (relative to delta(18)O-NO(3)(-)) versus delta(18) O-H(2)O (relative to delta(18)O-NO(3)(-)) yielded slopes of 0.76-0.80 and intercepts of 31-350/00. CONCLUSIONS: In soil between tea plant rows, the fraction of O-exchange between H(2)O and N(2)O precursors was approximately 80%. Assuming that denitrification dominated N(2)O production, the net (18)O-isotope effect for denitrification (NO(3)(-) reduction to N(2)O) was approximately 31-350/00, reflecting the upland condition of the tea field. PMID- 26377019 TI - Non-linear mixing effects on mass-47 CO2 clumped isotope thermometry: Patterns and implications. AB - RATIONALE: Mass-47 CO(2) clumped isotope thermometry requires relatively large (~20 mg) samples of carbonate minerals due to detection limits and shot noise in gas source isotope ratio mass spectrometry (IRMS). However, it is unreasonable to assume that natural geologic materials are homogenous on the scale required for sampling. We show that sample heterogeneities can cause offsets from equilibrium Delta(47) values that are controlled solely by end member mixing and are independent of equilibrium temperatures. METHODS: A numerical model was built to simulate and quantify the effects of end member mixing on Delta(47). The model was run in multiple possible configurations to produce a dataset of mixing effects. We verified that the model accurately simulated real phenomena by comparing two artificial laboratory mixtures measured using IRMS to model output. RESULTS: Mixing effects were found to be dependent on end member isotopic composition in delta(13)C and delta(18)O values, and independent of end member Delta(47) values. Both positive and negative offsets from equilibrium Delta(47) can occur, and the sign is dependent on the interaction between end member isotopic compositions. The overall magnitude of mixing offsets is controlled by the amount of variability within a sample; the larger the disparity between end member compositions, the larger the mixing offset. CONCLUSIONS: Samples varying by less than 2 0/00 in both delta(13)C and delta(18)O values have mixing offsets below current IRMS detection limits. We recommend the use of isotopic subsampling for delta(13)C and delta(18)O values to determine sample heterogeneity, and to evaluate any potential mixing effects in samples suspected of being heterogonous. PMID- 26377020 TI - Electron affinity evaluation for nitrobenzene derivatives using negative ion lifetime data. PMID- 26377021 TI - Respiratory modulations in the photoplethysmogram (DPOP) as a measure of respiratory effort. AB - DPOP is a measure of the strength of respiratory modulations present in the pulse oximetry photoplethysmogram (pleth) waveform. It has been proposed as a non invasive parameter for the prediction of the response to volume expansion in hypovolemic patients. The effect of resistive breathing on the DPOP parameter was studied to determine whether it may have an adjunct use as a measure of respiratory effort. Healthy volunteers were tasked to breathe at fixed respiratory rates over a range of airway resistances generated by a flow resistor inserted within a mouthpiece. Changes in respiratory efforts, effected by the subjects and measured as airway pressures at the mouth, were compared to DPOP values derived from a finger pulse oximeter probe. It was found that the increased effort to breathe manifests itself as an associated increase in DPOP. Further, a relationship between DPOP and percent modulation of the pleth waveform was observed. A version of the DPOP algorithm that corrects for low perfusion was implemented which resulted in an improved relationship between DPOP and PPV. Although a limited cohort of seven volunteers was used, the results suggest that DPOP may be useful as a respiratory effort parameter, given that the fluid level of the patient is maintained at a constant level over the period of analysis. PMID- 26377022 TI - Capnodynamic assessment of effective lung volume during cardiac output manipulations in a porcine model. AB - A capnodynamic calculation of effective pulmonary blood flow includes a lung volume factor (ELV) that has to be estimated to solve the mathematical equation. In previous studies ELV correlated to reference methods for functional residual capacity (FRC). The aim was to evaluate the stability of ELV during significant manipulations of cardiac output (CO) and assess the agreement for absolute values and trending capacity during PEEP changes at different lung conditions. Ten pigs were included. Alterations of alveolar carbon dioxide were induced by cyclic reoccurring inspiratory holds. The Sulphur hexafluoride technique for FRC measurements was used as reference. Cardiac output was altered by preload reduction and inotropic stimulation at PEEP 5 and 12 cmH2O both in normal lung conditions and after repeated lung lavages. ELV at baseline PEEP 5 was [mean (SD)], 810 (163) mL and decreased to 400 (42) mL after lavage. ELV was not significantly affected by CO alterations within the same PEEP level. In relation to FRC the overall bias (limits of agreement) was -35 (-271 to 201) mL, and percentage error 36 %. A small difference between ELV and FRC was seen at PEEP 5 cmH2O before lavage and at PEEP 12 cmH2O after lavage. ELV trending capability between PEEP steps, showed a concordance rate of 100 %. ELV was closely related to FRC and remained stable during significant changes in CO. The trending capability was excellent both before and after surfactant depletion. PMID- 26377023 TI - Data clustering methods for the determination of cerebral autoregulation functionality. AB - Cerebral blood flow is regulated over a range of systemic blood pressures through the cerebral autoregulation (CA) control mechanism. The COx measure based on near infrared spectroscopy (NIRS) has been proposed as a suitable technique for the analysis of CA as it is non-invasive and provides a simpler acquisition methodology than other methods. The COx method relies on data binning and thresholding to determine the change between intact and impaired autoregulation zones. In the work reported here we have developed a novel method of differentiating the intact and impaired CA blood pressure regimes using clustering methods on unbinned data. K-means and Gaussian mixture model algorithms were used to analyse a porcine data set. The determination of the lower limit of autoregulation (LLA) was compared to a traditional binned data approach. Good agreement was found between the methods. The work highlights the potential application of using data clustering tools in the monitoring of CA function. PMID- 26377024 TI - SAGIT(r): clinician-reported outcome instrument for managing acromegaly in clinical practice--development and results from a pilot study. AB - PURPOSE: The SAGIT instrument is a comprehensive clinician-reported outcome instrument assessing key features of acromegaly: signs and symptoms, associated comorbidities; growth hormone levels; insulin-like growth factor-1 levels; and tumor profile. The SAGIT instrument has been designed to assist endocrinologists managing acromegaly in practice. Here, we report on pre-testing (to assess ease of understanding and acceptability) and a pilot study (to assess relevance, ease of use, and utility in real-life conditions) (NCT02231593). METHODS: For pre testing, 11 endocrinologists completed the SAGIT instrument using patient medical records and were also interviewed. They subsequently completed a PRAgmatic Content and face validity Test (PRAC-Test((c))) to report their experiences using SAGIT, and feedback was used to revise the instrument. In the pilot study, nine endocrinologists completed the SAGIT instrument in real-time with patients belonging to three different categories (stable/controlled, active/uncontrolled acromegaly, treatment-naive), while four completed the instrument based on medical-record review. All participants then completed the PRAC-Test((c)) and their feedback was used to update the instrument. RESULTS: The SAGIT instrument was well accepted by endocrinologists, with most indicating that it was concise, practical, easy to understand, useful for assessing treatment response, and valuable as a component of the patient's medical record. The pilot study confirmed the instrument's acceptability, utility, and ease of use, and indicated its potential for distinguishing acromegaly clinical stages. CONCLUSIONS: The SAGIT instrument is promising as a tool for use by endocrinologists in everyday practice to assess the status and evolution of disease in patients with acromegaly and to guide treatment decision-making. PMID- 26377025 TI - Utilizing the protein corona around silica nanoparticles for dual drug loading and release. AB - A protein corona forms spontaneously around silica nanoparticles (SNPs) in serum containing media. To test whether this protein corona can be utilized for the loading and release of anticancer drugs we incorporated the hydrophilic doxorubicin, the hydrophobic meloxicam as well as their combination in the corona around SNPs. The application of corona-covered SNPs to osteosarcoma cells revealed that drug-free particles did not affect the cell viability. In contrast, SNPs carrying a protein corona with doxorubicin or meloxicam lowered the cell proliferation in a concentration-dependent manner. In addition, these particles had an even greater antiproliferative potential than the respective concentrations of free drugs. The best antiproliferative effects were observed for SNPs containing both doxorubicin and meloxicam in their corona. Co localization studies revealed the presence of doxorubicin fluorescence in the nucleus and lysosomes of cells exposed to doxorubicin-containing coated SNPs, suggesting that endocytotic uptake of the SNPs facilitates the cellular accumulation of the drug. Our data demonstrate that the protein corona, which spontaneously forms around nanoparticles, can be efficiently exploited for loading the particles with multiple drugs for therapeutic purposes. As drugs are efficiently released from such particles they may have a great potential for nanomedical applications. PMID- 26377026 TI - The role of strigolactones and ethylene in disease caused by Pythium irregulare. AB - Plant hormones play key roles in defence against pathogen attack. Recent work has begun to extend this role to encompass not just the traditional disease/stress hormones, such as ethylene, but also growth-promoting hormones. Strigolactones (SLs) are the most recently defined group of plant hormones with important roles in plant-microbe interactions, as well as aspects of plant growth and development, although the knowledge of their role in plant-pathogen interactions is extremely limited. The oomycete Pythium irregulare is a poorly controlled pathogen of many crops. Previous work has indicated an important role for ethylene in defence against this oomycete. We examined the role of ethylene and SLs in response to this pathogen in pea (Pisum sativum L.) at the molecular and whole-plant levels using a set of well-characterized hormone mutants, including an ethylene-insensitive ein2 mutant and SL-deficient and insensitive mutants. We identified a key role for ethylene signalling in specific cell types that reduces pathogen invasion, extending the work carried out in other species. However, we found no evidence that SL biosynthesis or response influences the interaction of pea with P. irregulare or that synthetic SL influences the growth or hyphal branching of the oomycete in vitro. Future work should seek to extend our understanding of the role of SLs in other plant interactions, including with other fungal, bacterial and viral pathogens, nematodes and insect pests. PMID- 26377027 TI - Facial emotion recognition in patients with subjective cognitive decline and mild cognitive impairment. AB - BACKGROUND: Deficits in facial emotion recognition (FER) have been shown to substantially impair several aspects in everyday life of affected individuals (e.g. social functioning). Presently, we aim at assessing differences in emotion recognition performance in three patient groups suffering from mild forms of cognitive impairment compared to healthy controls. METHODS: Performance on a concise emotion recognition test battery (VERT-K) of 68 patients with subjective cognitive decline (SCD), 44 non-amnestic (non-aMCI), and 25 amnestic patients (aMCI) with mild cognitive impairment (MCI) was compared with an age-equivalent sample of 138 healthy controls all of which were recruited within the framework of the Vienna Conversion to Dementia Study. Additionally, patients and controls underwent individual assessment using a comprehensive neuropsychological test battery examining attention, executive functioning, language, and memory (NTBV), the Beck Depression Inventory (BDI), and a measure of premorbid IQ (WST). RESULTS: Type of diagnosis showed a significant effect on emotion recognition performance, indicating progressively deteriorating results as severity of diagnosis increased. Between-groups effect sizes were substantial, showing non trivial effects in all comparisons (Cohen's ds from -0.30 to -0.83) except for SCD versus controls. Moreover, emotion recognition performance was higher in women and positively associated with premorbid IQ. CONCLUSIONS: Our findings indicate substantial effects of progressive neurological damage on emotion recognition in patients. Importantly, emotion recognition deficits were observable in non-amnestic patients as well, thus conceivably suggesting associations between decreased recognition performance and global cognitive decline. Premorbid IQ appears to act as protective factor yielding lesser deficits in patients showing higher IQs. PMID- 26377028 TI - Lewis Score--Prognostic Value in Patients with Isolated Small Bowel Crohn's Disease. AB - BACKGROUND AND AIMS: Small bowel capsule endoscopy (SBCE) allows mapping of small bowel inflammation in Crohn's disease (CD). We aimed to assess the prognostic value of the severity of inflammatory lesions, quantified by the Lewis score (LS), in patients with isolated small bowel CD. METHODS: A retrospective study was performed in which 53 patients with isolated small bowel CD were submitted to SBCE at the time of diagnosis. The Lewis score was calculated and patients had at least 12 months of follow-up after diagnosis. As adverse events we defined disease flare requiring systemic corticosteroid therapy, hospitalization and/or surgery during follow-up. We compared the incidence of adverse events in 2 patient subgroups, i.e. those with moderate or severe inflammatory activity (LS >=790) and those with mild inflammatory activity (135 <= LS < 790). RESULTS: The LS was >=790 in 22 patients (41.5%), while 58.5% presented with LS between 135 and 790. Patients with a higher LS were more frequently smokers (p = 0.01), males (p = 0017) and under immunosuppressive therapy (p = 0.004). In multivariate analysis, moderate to severe disease at SBCE was independently associated with corticosteroid therapy during follow-up, with a relative risk (RR) of 5 (p = 0.011; 95% confidence interval [CI] 1.5-17.8), and for hospitalization, with an RR of 13.7 (p = 0 .028; 95% CI 1.3-141.9). CONCLUSION: In patients with moderate to severe inflammatory activity there were higher prevalences of corticosteroid therapy demand and hospitalization during follow-up. Thus, stratifying the degree of small bowel inflammatory activity with SBCE and LS calculation at the time of diagnosis provided relevant prognostic value in patients with isolated small bowel CD. PMID- 26377029 TI - SURGICAL TREATMENT FOR INFECTED LONG BONE DEFECTS AFTER LIMB-THREATENING TRAUMA: APPLICATION OF LOCKED PLATE AND AUTOGENOUS CANCELLOUS BONE GRAFT. AB - BACKGROUND: Treatment strategies for bone defects include free bone grafting, distraction osteogenesis, and vascularized bone grafting. Because bone defect morphology is often irregular, selecting treatment strategies may be difficult. With the Masquelet technique, a fracture site is bridged and fixed with a locking plate after treating deep infection with antibiotic-containing cement, and a free cancellous bone-graft is concomitantly placed into the defects. This procedure avoids excessive bone resection. METHODS: We studied 6 patients who underwent surgical treatment for deep infection occurring after extremity trauma (2004 through 2009). Ages at surgery ranged from 29 to 59 years (largest age group: 30 s). Mean follow-up was 50.7 months (minimum/maximum: 36/72 months). One patient had complete amputation of the upper extremity, 3 open forearm fractures, 1 closed supracondylar femur fracture, and 1 open tibia fracture. In all patients, bone defects were filled with antibiotic-containing cement beads after infected site debridement. If bacterial culture of infected sites during curettage was positive, surgery was repeated to refill bone defects with antibiotic-containing cement beads. After confirmation of negative bacterial culture, osteosynthesis was performed, in which bone defects were bridged and fixed with locking plates. Concomitantly, crushed cancellous bone grafts harvested from the autogenous ilium was placed in the bone defects. RESULTS: Time from bone grafting and plate fixation to bone union was at least 3 and at most 6 months, 4 months on average. Infection relapsed in one patient with methicillin-resistant Staphylococcus aureus, necessitating vascularized fibular grafting which achieved bone union. No patients showed implant loosening or breakage or infection relapse after the last surgery during follow-up. CONCLUSION: The advantage of cancellous bone grafting include applicability to relatively large bone defects, simple surgical procedure, bone graft adjustability to bone defect morphology, rapid bone graft revascularization resulting in high resistance to infection, and excellent osteogenesis. PMID- 26377030 TI - Shear stress induces a longitudinal Ca(2+) wave via autocrine activation of P2Y1 purinergic signalling in rat atrial myocytes. AB - Atrial myocytes are exposed to shear stress during the cardiac cycle and haemodynamic disturbance. In response, they generate a longitudinally propagating global Ca(2+) wave. Here, we investigated the cellular mechanisms underlying the shear stress-mediated Ca(2+) wave, using two-dimensional confocal Ca(2+) imaging combined with a pressurized microflow system in single rat atrial myocytes. Shear stress of ~16 dyn cm(-2) for 8 s induced ~1.2 aperiodic longitudinal Ca(2+) waves (~79 MUm s(-1)) with a delay of 0.2-3 s. Pharmacological blockade of ryanodine receptors (RyRs) or inositol 1,4,5-trisphosphate receptors (IP3 Rs) abolished shear stress-induced Ca(2+) wave generation. Furthermore, in atrial myocytes from type 2 IP3R (IP3R2) knock-out mice, shear stress failed to induce longitudinal Ca(2+) waves. The phospholipase C (PLC) inhibitor U73122, but not its inactive analogue U73343, abolished the shear-induced longitudinal Ca(2+) wave. However, pretreating atrial cells with blockers for stretch-activated channels, Na(+) Ca(2+) exchanger, transient receptor potential melastatin subfamily 4, or nicotinamide adenine dinucleotide phosphate oxidase did not suppress wave generation under shear stress. The P2 purinoceptor inhibitor suramin, and the potent P2Y1 receptor antagonist MRS 2179, both suppressed the Ca(2+) wave, whereas the P2X receptor antagonist, iso-PPADS, did not alter it. Suppression of gap junction hemichannels permeable to ATP or extracellular application of ATP metabolizing apyrase inhibited the wave. Removal of external Ca(2+) to enhance hemichannel opening facilitated the wave generation. Our data suggest that longitudinally propagating, regenerative Ca(2+) release through RyRs is triggered by P2Y1-PLC-IP3R2 signalling that is activated by gap junction hemichannel mediated ATP release in atrial myocytes under shear stress. PMID- 26377031 TI - Evaluation of geriatric assessment in patients with chronic lymphocytic leukemia: Results of the CLL9 trial of the German CLL study group. AB - Multidimensional geriatric assessment (GA) has been demonstrated to predict outcomes in older patients with cancer. This study evaluated GA in a cohort of older patients with chronic lymphocytic leukemia (CLL). Seventy-five of 97 subjects with CLL who were enrolled in a clinical trial of the German CLL Study Group underwent GA prior to the start of study treatment (low-dose chemotherapy with fludarabine). GA included cumulative illness rating scale (CIRS), timed-up and-go (TUG) test, dementia detection (DEMTECT) test and instrumental activities of daily living (IADL) index. There was little correlation between CIRS, TUG, DEMTECT or IADL results and treatment toxicity, feasibility or efficacy in this study. CIRS and IADL had no statistically significant impact on overall prognosis. However, under-performance in TUG or DEMTECT test was strongly associated with poor survival. The latter findings provide a rationale to further investigate geriatric assessment in CLL and in the context with other CLL treatments. PMID- 26377032 TI - Performance of In Silico Tools for the Evaluation of UGT1A1 Missense Variants. AB - Variations in the gene encoding uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) are particularly important because they have been associated with hyperbilirubinemia in Gilbert's and Crigler-Najjar syndromes as well as with changes in drug metabolism. Several variants associated with these phenotypes are nonsynonymous single-nucleotide polymorphisms (nsSNPs). Bioinformatics approaches have gained increasing importance in predicting the functional significance of these variants. This study was focused on the predictive ability of bioinformatics approaches to determine the pathogenicity of human UGT1A1 nsSNPs, which were previously characterized at the protein level by in vivo and in vitro studies. Using 16 Web algorithms, we evaluated 48 nsSNPs described in the literature and databases. Eight of these algorithms reached or exceeded 90% sensitivity and six presented a Matthews correlation coefficient above 0.46. The best-performing method was MutPred, followed by Sorting Intolerant from Tolerant (SIFT). The prediction measures varied significantly when predictors such us SIFT, polyphen-2, and Prediction of Pathological Mutations on Proteins were run with their native alignment generated by the tool, or with an input alignment that was strictly built with UGT1A1 orthologs and manually curated. Our results showed that the prediction performance of some methods based on sequence conservation analysis can be negatively affected when nsSNPs are positioned at the hypervariable or constant regions of UGT1A1 ortholog sequences. PMID- 26377033 TI - The transduction pattern of IL-12-encoding lentiviral vectors shapes the immunological outcome. AB - In situ modification of antigen-presenting cells garnered interest in cancer immunotherapy. Therefore, we developed APC-targeted lentiviral vectors (LVs). Unexpectedly, these LVs were inferior vaccines to broad tropism LVs. Since IL-12 is a potent mediator of antitumor immunity, we evaluated whether this proinflammatory cytokine could enhance antitumor immunity of an APC-targeted LV based vaccine. Therefore, we compared subcutaneous administration of broad tropism LVs (VSV-G-LV) with APC-targeted LVs (DC2.1-LV)-encoding enhanced GFP and ovalbumin, or IL-12 and ovalbumin in mice. We show that codelivery of IL-12 by VSV-G-LVs or DC2.1-LVs augments CD4(+) or CD8(+) T-cell proliferation, respectively. Furthermore, we demonstrate that codelivery of IL-12 enhances the CD4(+) TH 1 profile irrespective of its delivery mode, while an increase in cytotoxic and therapeutic CD8(+) T cells was only induced upon VSV-G-LV injection. While codelivery of IL-12 by DC2.1-LVs did not enhance CD8(+) T-cell performance, it increased expression of inhibitory checkpoint markers Lag3, Tim3, and PD-1. Finally, the discrepancy between CD4(+) T-cell stimulation with and without functional CD8(+) T-cell stimulation by VSV-G- and DC2.1-LVs is partly explained by the observation that IL-12 relieves CD8(+) T cells from CD4(+) T cell help, implying that a T(H)1 profile is of minor importance for antitumor immunotherapy if IL-12 is exogenously delivered. PMID- 26377034 TI - Suspended graphene devices with local gate control on an insulating substrate. AB - We present a fabrication process for graphene-based devices where a graphene monolayer is suspended above a local metallic gate placed in a trench. As an example we detail the fabrication steps of a graphene field-effect transistor. The devices are built on a bare high-resistivity silicon substrate. At temperatures of 77 K and below, we observe the field-effect modulation of the graphene resistivity by a voltage applied to the gate. This fabrication approach enables new experiments involving graphene-based superconducting qubits and nano electromechanical resonators. The method is applicable to other two-dimensional materials. PMID- 26377035 TI - Multicompartmental, multilayered probucol microcapsules for diabetes mellitus: Formulation characterization and effects on production of insulin and inflammation in a pancreatic beta-cell line. AB - CONTEXT: We have shown that the primary bile acid, cholic acid (CA), has anti diabetic effects in vivo. Probucol (PB) is a lipophilic drug with potential applications in type 2 diabetes (T2D). OBJECTIVE: This study aimed to encapsulate CA with PB and examine the formulation and surface characteristics of the microcapsules. We also tested the microcapsules' biological effects on pancreatic beta-cells. METHODS: Using the polymer, sodium alginate (SA), two formulations were prepared: PB-SA (control), and PB-CA-SA (test). Complete characterizations of the morphology, shape, size, chemical, thermal, and rheological properties, swelling and mechanical strength, cross-sectional imaging (Micro CT), stability, Zeta-potential, drug contents, and PB release profile were carried out, at different temperature and pH values. The microcapsules were applied to a NIT-1 cell culture and the supernatant was analyzed for insulin and TNF-alpha concentrations. RESULTS: CA incorporation optimized the PB microcapsules, which exhibited pseudoplastic-thixotropic rheological characteristics. The size of the microcapsules remained similar after CA addition, and the microcapsules showed even drug distribution and no chemical alterations of the excipients. Micro-CT imaging, differential scanning calorimetry, Fourier transform infrared spectroscopy, scanning electron microscopy, and energy-dispersive X-ray spectroscopy showed consistent microcapsules with uniform shape and morphology. PB-CA-SA microcapsules enhanced NIT-1 cell viability under hyperglycemic states and resulted in improved insulin release as well as reduced cytokine production at the physiological glucose levels. CONCLUSIONS: The addition of the primary bile acid, CA, improved the physical properties of the microcapsules and enhanced their pharmacological activity in vitro, suggesting potential applications in diabetes treatment. PMID- 26377037 TI - Incidence of Ct scan-detected pulmonary embolism in patients with oncogene addicted, advanced lung adenocarcinoma. AB - BACKGROUND: Patients with stage IIIB-IV lung adenocarcinoma are at high-risk for pulmonary embolism (PE). In these patients, EGFR and KRAS mutations as well as EML4/ALK rearrangements are recognized as "drivers" and as targets for therapy. Data on the incidence of PE in oncogene-addicted lung cancer patients are limited. AIMS: The aims of this study were to evaluate the incidence of CT scan detected PE in patients with stage IIIB-IV lung adenocarcinoma and to assess the potential correlation between the presence of these oncogenes and the PE risk. METHODS: Baseline staging or re-staging chest contrast-enhanced CT scans of patients with stage IIIB-IV lung adenocarcinoma were retrospectively reviewed and adjudicated for the presence of PE. Data on the oncogene drivers (EGFR, KRAS or EML4/ALK) of the same patients were collected. RESULTS: A total of 173 patients with lung adenocarcinoma were included in the study. 24.8% of patients were EGFR mutated (31/125), 21.6% were KRAS mutated (27/125) and 13.6% hadan EML4/ALK rearrangement (17/125). 41 patients had a CT-detected PE (23.7%). A PE was observed in 5 patients with EGFR mutation (16.2%), in 5 patients with KRAS mutation (18.5%), in 8 patients with ELM4/ALK mutation (47.1%). The presence of ELM4/ALK rearrangement was associated with an increased risk of PE [HR:2.06 (95%CI 1.08- 3.55)]. Risk of PE was not found to be associated with EGFR or KRAS mutations. CONCLUSIONS: Patients with advanced lung adenocarcinoma were at high risk for PE. The presence of EML4/ALK rearrangement was associated with an increased PE risk. PMID- 26377039 TI - Single-Nanoparticle Collision Events: Tunneling Electron Transfer on a Titanium Dioxide Passivated n-Silicon Electrode. AB - Single-nanoparticle collisions were observed on an n-type silicon electrode (600 MUm diameter) passivated by a thin layer of amorphous TiO2, where the current steps occurred by tunneling electron transfer. The observed collision frequency was in reasonable agreement with that predicted from theory. The isolated electrode, after a collision experiment, with a Pt/TiO2/n-Si architecture was shown to retain the photoelectrochemical properties of n-Si without photocorrosion or current decay. The Pt/TiO2/n-Si electrode produced 19 mA cm(-2) of photocurrent density under 100 mW cm(-2) irradiation from a xenon lamp during oxygen evolution without current fading for over 12 h. PMID- 26377036 TI - Correlation of BACH1 and Hemoglobin E/Beta-Thalassemia Globin Expression. AB - OBJECTIVE: The diverse clinical phenotype of hemoglobin E (HbE)/beta-thalassemia has not only confounded clinicians in matters of patient management but has also led scientists to investigate the complex mechanisms involved in maintaining the delicate red cell environment where, even with apparent similarities of alpha- and beta-globin genotypes, the phenotype tells a different story. The BTB and CNC homology 1 (BACH1) protein is known to regulate alpha- and beta-globin gene transcriptions during the terminal differentiation of erythroid cells. With the mutations involved in HbE/beta-thalassemia disorder, we studied the role of BACH1 in compensating for the globin chain imbalance, albeit for fine-tuning purposes. MATERIALS AND METHODS: A total of 47 HbE/beta-thalassemia samples were analyzed using real-time quantitative polymerase chain reaction and correlated with age, sex, red blood cell parameters, globin gene expressions, and some clinical data. RESULTS: The BACH1 expression among the beta-thalassemia intermedia patients varied by up to 2-log differences and was positively correlated to age; alpha-, beta-, and gamma-globin gene expression level; and heme oxygenase 1 protein. BACH1 was also negatively correlated to reticulocyte level and had a significant correlation with splenectomy. CONCLUSION: This study indicates that the expression of BACH1 could be elevated as a compensatory mechanism to decrease the globin chain imbalance as well as to reduce the oxidative stress found in HbE/beta-thalassemia. PMID- 26377038 TI - Efficient inhibition of human AP endonuclease 1 (APE1) via substrate masking by abasic site-binding macrocyclic ligands. AB - Bis-naphthalene macrocycles, which bind with high affinity and selectivity to abasic sites in DNA, efficiently inhibit their cleavage by APE1 (IC50 = 55-60 nM in the kinetic assay with a model THF substrate). These results demonstrate that substrate masking by non-covalent abasic-site ligands is an efficient strategy for inhibition of APE1. PMID- 26377040 TI - Preparation of phenyl-functionalized magnetic mesoporous silica microspheres for the fast separation and selective enrichment of phenyl-containing peptides. AB - Peptide enrichment before mass spectrometry analysis is essential for large-scale peptidomic studies, but challenges still remain. Herein, magnetic mesoporous silica microspheres with phenyl group modified interior pore walls were prepared by a facile sol-gel coating strategy, and were successfully applied for selective enrichment of phenyl-containing peptides in complex biological samples. The newly prepared nanomaterials possessed abundant silanol groups in the exterior surface and numerous phenyl groups in the interior pore walls, as well as a large surface area (592.6 m2 /g), large pore volume (0.33 cm3 /g), uniform mesopores (3.8 nm), strong magnetic response (29.3 emu/g), and good dispersibility in aqueous solution. As a result of the unique structural properties and size-exclusion effect, the core-shell phenyl-functionalized magnetic mesoporous silica microspheres exhibited excellent performance in fast separation and selective enrichment of phenyl-containing peptides, and the adsorption capacity for bradykinin reached 22.55 mg/g. In addition, selective enrichment of phenyl containing peptides from complex samples that are consist of peptides, large proteins, and human serum were achieved by using the as-prepared microspheres, followed by high-performance liquid chromatography with ultraviolet detection and electrospray ionization quadrupole time-of-flight mass spectrometry analysis. These results demonstrated the as-prepared microspheres would be a potential candidate for endogenous phenyl-containing peptides enrichment and biomarkers discovery in peptidome analysis. PMID- 26377042 TI - First Observation of Hemoglobin Kansas [beta102(G4)Asn->Thr, AAC>ACC] in the Turkish Population. PMID- 26377041 TI - Promoting patient-centred care in psoriatic arthritis: a multidisciplinary European perspective on improving the patient experience. AB - Patients with psoriatic arthritis (PsA) may not be optimally treated. The impact of the disease extends beyond skin and joint symptoms, impairing quality of life. This indicates that the adoption of a patient-focused approach to PsA management is necessary. An expert multidisciplinary working group was convened, with the objective of developing an informed perspective on current best practice and needs for the future management of PsA. Topics of discussion included the barriers to current best practice and calls to action for the improvement of three areas in PsA management: early and accurate diagnosis of PsA, management of disease progression and management of the impact of the condition on the patient. The working group agreed that, to make best use of the available of diagnostic tools, clinical care recommendations and effective treatments, there is a clear need for healthcare professionals from different disciplines to collaborate in the management of PsA. By facilitating appropriate and rapid referral, providing high quality information about PsA and its treatment to patients, and actively involving patients when choosing management plans and setting treatment goals, management of PsA can be improved. The perspective of the working group is presented here, with recommendations for the adoption of a multidisciplinary, patient-focused approach to the management of PsA. PMID- 26377043 TI - Structural self-organization of C60 and cisplatin in physiological solution. AB - The specific features of structural self-organization of C60 fullerene and antitumor drug cisplatin (Cis) in physiological solution (0.9% NaCl) have been investigated by means of small-angle neutron scattering, scanning electron and atomic force microscopies, as well as isothermal titration calorimetry, dynamic light scattering and UV-Vis spectroscopy. The formation of C60 + Cis complexes, has been reported, unveiling the mechanism of medico-biological synergy observed during administration of the mixture of these drugs. PMID- 26377044 TI - Potentially functional polymorphisms in PAK1 are associated with risk of lung cancer in a Chinese population. AB - P21-activated kinase 1(PAK1) plays an important role in the regulation of cell morphogenesis, motility, mitosis, and angiogenesis and has been implicated with tumorigenesis and tumor progression. We hypothesized that functional polymorphisms in PAK1 gene may modify the risk of lung cancer. We screened four potentially functional polymorphisms (rs2154754, rs3015993, rs7109645, and rs2844337) in PAK1 gene and evaluated the association between the genetic variants and lung cancer risk in a case-control study including 1341 lung cancer cases and 1982 cancer-free controls in a Chinese population. We found that variant allele of rs2154754 was significantly associated with a decreased risk of lung cancer (OR = 0.85, 95% CI: 0.77-0.95, P = 0.004), meanwhile the result of rs3015993 was marginal (OR = 0.90, 95%CI: 0.81-1.00, P = 0.044). After multiple comparisons, rs2154754 was still significantly associated with the lung cancer risk (P < 0.0125 for Bonferroni correction). We also detected a significant interaction between rs2154754 genotypes and smoking levels on lung cancer risk (P = 0.042). Combined analysis of these two polymorphisms showed a significant allele-dosage association between the number of protective alleles and reduced risk of lung cancer (Ptrend = 0.008). These findings indicate that genetic variants in PAK1 gene may contribute to susceptibility to lung cancer in the Chinese population. PMID- 26377045 TI - Investigating the role of shape on the biological impact of gold nanoparticles in vitro. AB - AIM: To investigate the influence of gold nanoparticle geometry on the biochemical response of Calu-3 epithelial cells. MATERIALS & METHODS: Spherical, triangular and hexagonal gold nanoparticles (GNPs) were used. The GNP-cell interaction was assessed via atomic absorption spectroscopy (AAS) and transmission electron microscopy (TEM). The biochemical impact of GNPs was determined over 72 h at (0.0001-1 mg/ml). RESULTS: At 1 mg/ml, hexagonal GNPs reduced Calu-3 viability below 60%, showed increased reactive oxygen species production and higher expression of proapoptotic markers. A cell mass burden of 1:2:12 as well as number of GNPs per cell (2:1:3) was observed for spherical:triangular:hexagonal GNPs. CONCLUSION: These findings do not suggest a direct shape-toxicity effect. However, do highlight the contribution of shape towards the GNP-cell interaction which impacts upon their intracellular number, mass and volume dose. PMID- 26377046 TI - Recent developments in poly(dopamine)-based coatings for biomedical applications. AB - The success of polymer coatings for biomedical applications is undeniable. Among the very successful examples are poly(dopamine) (PDA) films due to their simplicity in deposition and beneficial interaction with biomolecules and cells. The aim of this review is to highlight the findings and achievement of PDA in nanomedicine since 2011. We discuss the progress that has been made to elucidate the structure of PDA and novel aspects considering the assembly of PDA-based films on diverse substrates. We highlight the newest results considering the biological evaluation PDA-based coatings to control cell behavior and the use of PDA in biosensing. The popularity of PDA remains unchanged, but the research efforts start to be consolidated toward more specific aims and clinical applications. PMID- 26377048 TI - Time-Dependent Metabolism of Luteolin by Human UDP-Glucuronosyltransferases and Its Intestinal First-Pass Glucuronidation in Mice. AB - Luteolin is a well-known flavonoid with various pharmacological properties but has low bioavailability due to glucuronidation. This study investigated the time course of luteolin glucuronidation by 12 human UDP-glucuronosyltransferases (UGTs) and its intestinal first-pass metabolism in mice. Six metabolites, including two novel abundant diglucuronides [3',7-O-diglucuronide (diG) and 4',7 diG] and four known ones, were identified. UGT1A6 and UGT1A9 generated almost only monoglucuronides (G's). The production of 3',7-diG followed a sequential time-dependent process along with decrease of 3'-G mainly by UGT1A1, indicating that 3',7-diG was produced from 3'-G. Metabolism in mice intestine differed from that in humans. Probenecid, a nonspecific UGT inhibitor, did not affect absorption but significantly inhibited production of 7-, 4'-, and 3'-G, and enhanced the formation of another novel metabolite, 5-G, in mice. In conclusion, diglucuronide formation is time-dependent and isoform-specific. UGT1A1 preferentially generates diG, whereas UGT1A6 and UGT1A9 share a preference for G production. PMID- 26377047 TI - Serum protein adsorption and excretion pathways of metal nanoparticles. AB - While the synthesis of metal nanoparticles (NPs) with fascinating optical and electronic properties have progressed dramatically and their potential biomedical applications were also well demonstrated in the past decade, translation of metal NPs into the clinical practice still remains a challenge due to their severe accumulation in the body. Herein, we give a brief review on size-dependent material properties of metal NPs and their potential biomedical applications, followed by a summary of how structural parameters such as size, shape and charge influence their interactions with serum protein adsorption, cellular uptake and excretion pathways. Finally, the future challenges in minimizing serum protein adsorption and expediting clinical translation of metal NPs were also discussed. PMID- 26377049 TI - A Hemophagocytic Lymphohistiocytosis Case with Newly Defined UNC13D (c.175G>C; p.Ala59Pro) Mutation and a Rare Complication. AB - Hemophagocytic lymphohistiocytosis (HLH) represents a severe hyperinflammatory condition with cardinal symptoms of prolonged fever, cytopenias, hepatosplenomegaly, and hemophagocytosis by activated, morphologically benign macrophages with impaired function of natural killer cells and cytotoxic T lymphocytes. A 2-month-old girl, who was admitted with fever, was diagnosed with HLH and her genetic examination revealed a newly defined mutation in the UNC13D (c.175G>C; p.Ala59Pro) gene. She was treated with dexamethasone, etoposide, and intrathecal methotrexate. During the second week of treatment, after three doses of etoposide, it was noticed that there was a necrotic plaque lesion on the soft palate. Pathologic examination of debrided material in PAS and Grocott staining revealed lots of septated hyphae, which was consistent with aspergillosis infection. Etoposide was stopped and amphotericin B treatment was given for six weeks. HLH 2004 protocol was completed to eight weeks with cyclosporine A orally. There was no patient with invasive aspergillosis infection as severe as causing palate and nasal septum perforation during HLH therapy. In immunocompromised patients, fungal infections may cause nasal septum perforation and treatment could be achieved by antifungal therapy and debridement of necrotic tissue. PMID- 26377050 TI - Re: Theileria orientalis: a review. PMID- 26377052 TI - Molecular oxygen reduction catalyzed by a highly oxidative resistant complex of cobalt-hydrazone at the liquid/liquid interface. AB - A new complex of Co(III) using an oxidative stable hydrazone ligand, CoL, was synthesized and characterized by elemental analysis, spectroscopic methods and single crystal X-ray analysis where HL is bis-[(E)-N'-(phenyl(pyridin-2 yl)methylene)]carbohydrazide. X-ray analysis revealed that the complex is mononuclear and the coordination environment around the Co(III) core is trans [CoN4Cl2]. The catalytic activity of the complex in the oxygen reduction reaction was investigated. The complex is a highly oxidative resistant cobalt-hydrazone which can efficiently catalyze the reduction of oxygen (O2) by a weak electron donor ferrocene, (Fc), at the polarized water/1,2-dichloroethane (DCE) interface. Oxygen reduction is coupled with proton transfer from water to the organic phase to form hydrogen peroxide, which is extracted into the aqueous phase. PMID- 26377051 TI - Self-reported use of novel psychoactive substances in a US nationally representative survey: Prevalence, correlates, and a call for new survey methods to prevent underreporting. AB - BACKGROUND: In recent years, there has been an increase in emergence and use of novel psychoactive substances (NPS) in the US and worldwide. However, there is little published epidemiological survey data estimating the prevalence of use in the US. METHOD: Data on self-reported NPS use came from the National Survey of Drug Use and Health (2009-2013), a national representative sample of non institutionalized individuals in the US. Subjects were asked to provide names of (non-traditional) drugs they used that they were not specifically asked about. We examined lifetime prevalence and sociodemographic correlates of self-reported use of new and uncommon synthetic drugs (NPS) among subjects ages 12-34-years-old. RESULTS: 1.2% of subjects self-reported any use of the 57 NPS we examined. Use of psychedelic tryptamines (primarily DMT) was most common, followed by psychedelic phenethylamines (e.g., 2C series) and synthetic cannabinoids. Prevalence of self reported use of NPS increased from 2009 to 2013 and use was most common among males, whites, older subjects, those of lower income, and among those residing in cities. Lifetime use of various other illicit drugs (e.g., LSD, cocaine, ecstasy/MDMA) was highly prevalent among NPS users. CONCLUSION: This the first study reporting on use of a variety of NPS in a nationally representative US sample; however, use appears to be underreported as other national data suggest higher rates of NPS (e.g., synthetic cannabinoid) use. Developing more adaptable survey tools and systematically assessing NPS use would allow researchers to ask about hundreds of NPS and improve reporting as new drugs continue to rapidly emerge. PMID- 26377053 TI - Prevention of diabetes: more answers, more questions. PMID- 26377055 TI - Erratum. PMID- 26377056 TI - Mentorship in Academic Medicine: A Catalyst of Talents. PMID- 26377054 TI - Long-term effects of lifestyle intervention or metformin on diabetes development and microvascular complications over 15-year follow-up: the Diabetes Prevention Program Outcomes Study. AB - BACKGROUND: Effective prevention is needed to combat the worldwide epidemic of type 2 diabetes. We investigated the long-term extent of beneficial effects of lifestyle intervention and metformin on diabetes prevention, originally shown during the 3-year Diabetes Prevention Program (DPP), and assessed whether these interventions reduced diabetes-associated microvascular complications. METHODS: The DPP (1996-2001) was a randomised trial comparing an intensive lifestyle intervention or masked metformin with placebo in a cohort selected to be at very high risk of developing diabetes. All participants were offered lifestyle training at the end of the DPP. 2776 (88%) of the surviving DPP cohort were followed up in the DPP Outcomes Study (DPPOS, Sept 1, 2002, to Jan 2, 2014) and analysed by intention to treat on the basis of their original DPP assignment. During DPPOS, the original lifestyle intervention group was offered lifestyle reinforcement semi-annually and the metformin group received unmasked metformin. The primary outcomes were the development of diabetes and the prevalence of microvascular disease. For the assessment of microvascular disease, we used an aggregate microvascular outcome, composed of nephropathy, retinopathy, and neuropathy. FINDINGS: During a mean follow-up of 15 years, diabetes incidence was reduced by 27% in the lifestyle intervention group (hazard ratio 0.73, 95% CI 0.65-0.83; p<0.0001) and by 18% in the metformin group (0.82, 0.72-0.93; p=0.001), compared with the placebo group, with declining between-group differences over time. At year 15, the cumulative incidences of diabetes were 55% in the lifestyle group, 56% in the metformin group, and 62% in the placebo group. The prevalences at the end of the study of the aggregate microvascular outcome were not significantly different between the treatment groups in the total cohort (placebo 12.4%, 95% CI 11.1-13.8; metformin 13.0%, 11.7-14.5; lifestyle intervention 11.3%, 10.1-12.7). However, in women (n=1887) the lifestyle intervention was associated with a lower prevalence (8.7%, 95% CI 7.4-10.2) than in the placebo (11.0%, 9.6-12.6) and metformin (11.2%, 9.7-12.9) groups, with reductions in the lifestyle intervention group of 21% (p=0.03) compared with placebo and 22% (p=0.02) compared with metformin. Compared with participants who developed diabetes, those who did not develop diabetes had a 28% lower prevalence of microvascular complications (relative risk 0.72, 95% CI 0.63-0.83; p<0.0001). INTERPRETATION: Lifestyle intervention or metformin significantly reduced diabetes development over 15 years. There were no overall differences in the aggregate microvascular outcome between treatment groups; however, those who did not develop diabetes had a lower prevalence of microvascular complications than those who did develop diabetes. This result supports the importance of diabetes prevention. FUNDING: National Institute of Diabetes and Digestive and Kidney Diseases. PMID- 26377057 TI - Neonatal Outcome of the Late Preterm Infant (34 to 36 Weeks): The Singapore Story. AB - INTRODUCTION: Late preterm (LP) neonates (34 to 36 weeks gestation) are often managed like term neonates though current literature has identified them to have greater complications. The primary objective of our study was to evaluate and compare morbidity and resource utilisation in LPs especially in view of paucity of Asian studies in this regard. MATERIALS AND METHODS: A retrospective audit was carried out on 12,459 neonates born in KK Women's and Children's Hospital (KKWCH). The chief outcome measures were hypoglycaemia, hypothermia, respiratory morbidity, feeding problems and neonatal jaundice. Resource utilisation included neonatal intensive care unit (NICU) admission, mechanical ventilation, parenteral nutrition and length of hospitalisation. RESULTS: Of 12,459 deliveries, 1221 (10%) were LP deliveries with a significantly increasing trend of 8.6% to 10% from 2002 to 2008 (P = 0.001). Neonatal morbidity in the form of hypoglycaemia (34 weeks vs 35 to 36 weeks vs term: 26% vs 16% vs 1%); hypothermia (5% vs 1.7% vs 0.2%); feeding difficulties (30% vs 9% vs 1.4%); respiratory distress syndrome (RDS) (4% vs 1% vs 0.1%); transient tachypnea of the newborn (TTNB) (23% vs 8% vs 3%) and neonatal jaundice (NNJ) needing phototherapy (63% vs 24% vs 8%), were significantly different between the 3 groups, with highest incidence in 34-week old infants. Resource utilisation including intermittent positive pressure ventilation (IPPV) (15% vs 3.5% vs 1%), total parenteral nutrition/intravenous (TPN/IV) (53% vs 17% vs 3%) and length of stay (14 +/- 22 days vs 4 +/- 4.7 days vs 2.6 +/- 3.9 days) was also significantly higher (P <0.001) in LPs. CONCLUSION: LP neonates had significantly higher morbidity and resource utilisation compared to term infants. Among the LP group, 34-week-old infants had greater complications compared to infants born at 35 to 36 weeks. PMID- 26377058 TI - A Review of Back Injury Cases Notified to the Ministry of Manpower from 2011 to 2012. AB - INTRODUCTION: In Singapore, the notification of workplace accidents and occupational diseases is a legal requirement under the Workplace Safety and Health (Incident Reporting) Regulations. This review is to identify back injury cases with physical work stresses and propose recommendations for preventive measures. MATERIALS AND METHODS: Cases involving back injuries notified to the Ministry of Manpower (MOM) from 1 January 2011 to 31 December 2012 were reviewed. Using predefined criteria, cases with physical work stresses were identified and the associated variables analysed. RESULTS: A total of 1124 notifications involving back injuries were received from 2011 to 2012; 579 cases (52%) were identified to have physical work stresses, of which 447 cases (77%) were males and 375 (64%) of them were between the ages of 21 to 40 years. The commonest physical work stresses were carrying (35%), awkward postures (22%) and lifting (20%). Majority of the cases came from the following sectors: construction (14%), accommodation and food services (12%), transport and storage (12%), manufacturing (10%) and wholesale and retail trade (10%). CONCLUSION: We identified the main physical work stresses in the back injury cases as carrying, awkward postures and lifting. The common industries involved were construction, accommodation and food services, and transport and storage sectors. This is useful for programmes aimed at reducing physical work stresses which can lead to improved work and health outcomes for our workers. PMID- 26377059 TI - Sevoflurane Output in the Isoflurane/Halothane Diamedica Draw-over Vaporiser. AB - INTRODUCTION: Draw-over anaesthesia remains an attractive option for conduct of anaesthesia in austere conditions. The Diamedica Draw-over Vaporiser (DDV) is a modern draw-over vaporiser and has separate models for isoflurane/halothane and sevoflurane. MATERIALS AND METHODS: A laboratory study was done to measure sevoflurane output in an isoflurane/ halothane DDV. We did 3 series of experiments with the isoflurane/halothane DDV. We measured anaesthetic agent output in both push-over and draw-over setups, and at minute ventilation of 6 L/min and 3 L/min. Series 1 experiment was done with isoflurane in the DDV at ambient temperature of 20 degrees C. Series 2 experiment was done with sevoflurane in the DDV at ambient temperature of 20 degrees C. Series 3 experiment was done with sevoflurane in the DDV and with the DDV placed in a water bath of 40 degrees C. RESULTS: The sevoflurane output was found to be two thirds of the isoflurane/ halothane DDV dial setting at ambient temperature of 20 degrees C. With the DDV in a 40 degrees C water bath, the sevoflurane output was found to be about the isoflurane/ halothane DDV dial settings. CONCLUSION: In our experiment, we show that it is possible to use sevoflurane in an isoflurane/halothane DDV. PMID- 26377060 TI - Patterns and Predictors of Dropout from Mental Health Treatment in an Asian Population. AB - INTRODUCTION: Studies examining mental health treatment dropout have primarily focused on Western populations and less so on Asian samples. The current study explored the prevalence and correlates of mental health treatment dropout across the various healthcare sectors in Singapore. MATERIALS AND METHODS: Data was utilised from the Singapore Mental Health Study (SMHS), a cross-sectional epidemiological survey conducted among an adult population (n = 6616) aged 18 years and above. Statistical analyses were done on a subsample of respondents (n = 55) who had sought treatment from the various treatment providers (i.e. mental health, medical, social services and religious healers) in the past 12 months. The World Mental Health (WMH) Composite International Diagnostic Interview version 3.0 (CIDI 3.0) was used to determine diagnoses of mental disorders, chronic medical disorders and service utilisation. RESULTS: Of those who had received treatment, 37.6% had ended treatment prematurely, 23.2% had completed treatment and 39.2% were still in treatment. The religious and spiritual sector (83.1%) had the highest dropout, followed by the general medical sector (34.6%), mental health services sector (33.9%) and the social services sector (30%). Marital status emerged as the only sociodemographic factor that significantly predicted treatment dropout-with those who were married being significantly less likely to drop out than those who were single. CONCLUSION: The overall dropout rate across the various healthcare sectors was comparable to past studies. While the small sample size limits the generalisability of findings, the current study provides useful insight into treatment dropout in an Asian population. PMID- 26377061 TI - Underutilisation of Guideline-based Therapy Primary Prevention among Patients Presenting with AF-related Ischaemic Stroke. PMID- 26377062 TI - Non-Urgent Paediatric Emergency Department Visits: Why Are They So Common? A Singapore Perspective. PMID- 26377063 TI - Single Pulse Electrical Stimulation to identify epileptogenic cortex: Clinical information obtained from early evoked responses. AB - OBJECTIVE: Single Pulse Electrical Stimulation (SPES) probes epileptogenic cortex during electrocorticography. Two SPES responses are described: pathological delayed responses (DR, >100 ms) associated with the seizure onset zone (SOZ) and physiological early responses (ER, <100 ms) that map cortical connectivity. We analyzed properties of ERs, including frequencies >80 Hz, in the SOZ and seizure propagation areas. METHODS: We used data from 12 refractory epilepsy patients. SPES consisted of 10 pulses of 1 ms, 4-8 mA and 5s interval on adjacent electrodes pairs. Data were available at 2048 samples/s for six and 512 samples/s (22 bits) for eight patients and analyzed in the time-frequency (TF) and time domain (TD). RESULTS: Electrodes with ERs were stronger associated with SOZ than non-SOZ electrodes. ERs with frequency content >80 Hz exist and are specific for SOZ channels. ERs evoked by stimulation of seizure onset electrodes were associated with electrodes involved in seizure propagation. CONCLUSION: Analysis of ERs can reveal aspects of pathology, manifested by association with seizure propagation and areas with high ER numbers that coincide with the SOZ. SIGNIFICANCE: Not only DRs, but also ERs could have clinical value for mapping epileptogenic cortex and help to unravel aspects of the epileptic network. PMID- 26377064 TI - Posterior Cologastric Anastomosis: An Effective Antireflux Mechanism in Colonic Replacement of the Esophagus. AB - BACKGROUND: The colon may be used to replace a portion of the esophagus in pediatric patients, but prevention of gastrocolic reflux is a concern. We report our experience with the retrosternal colon bypass, and the effect of combining the procedure with a posterior cologastric anastomosis on prevention of gastrocolic reflux. METHODS: The study included 35 consecutive pediatric patients who underwent retrosternal colon bypass during the period of 2010 through 2014. In standard practice, the cologastric anastomosis is performed at the anterior gastric wall. Lately, we modified our technique by shifting the cologastric anastomosis to the back of the stomach away from the anterior adhesions around the gastrostomy. In follow-up, a gastrogram was performed to check for gastrocolic reflux. RESULTS: The indication for esophageal replacement was postcorrosive esophageal stricture in 19 patients and long gap esophageal atresia in 16 patients. Their mean ages were 51 and 16 months, respectively. No gastrocolic reflux was detected with the posterior cologastric anastomosis, whereas reflux was always present with the anterior cologastric anastomosis. We had two mortalities and one major morbidity (hematemesis and failure to thrive) that were related to regurgitation of gastric contents into the colonic conduit. The last patient was successfully managed by transferring the cologastric anastomosis from the front to the back of the stomach, with marked symptomatic and radiologic improvement. CONCLUSIONS: After colonic replacement of the esophagus, the gastrocolic reflux represents a functional problem that may lead to serious complications. Combining a posterior cologastric anastomosis with retrosternal colon bypass is an effective way to avoid this problem. PMID- 26377065 TI - Pancytopenia in a patient with cystinosis secondary to myelosuppression from cystine crystal deposition: a case report. AB - INTRODUCTION: Cystinosis is a rare metabolic genetic disorder caused by a mutation in the cystinosin lysosomal cystine transporter gene. Clinically, it is characterized by systemic accumulation of cystine crystals in tissues causing end organ dysfunction in the kidney, eyes, muscles, and other organs in the body. In very rare cases, it can also involve the bone marrow and the resulting cystine crystal deposition can cause myelosuppression leading to pancytopenia. CASE PRESENTATION: Here we report the case of a 26-year-old white woman with cystinosis and other complex medical comorbidities who developed pancytopenia. She was worked up extensively and ruled out for common causes of pancytopenia (infectious disorders, vitamin deficiencies secondary to gastrointestinal malabsorption, rheumatologic, and hematologic disorders). On bone marrow biopsy she was found to have extensive deposits of cystine crystals, which was thought to be the cause of her myelosuppression leading to her pancytopenia. As a result, by treating her underlying cystinosis more aggressively we were able to observe an improvement in her pancytopenia a few months afterwards. CONCLUSIONS: Pancytopenia secondary to myelosuppression from cystine crystal deposition in the bone marrow is a very rare complication that has been reported in only a handful of case reports. This case illustrates the importance of keeping a broad differential diagnosis and systematically ruling out common causes of pancytopenia. It also demonstrates the importance of bone marrow biopsies in the evaluation of unexplained pancytopenia. PMID- 26377066 TI - The combined effect of age and body mass index on outcomes in foregut surgery: a regression model analysis of the National Surgical Quality Improvement Program data. AB - BACKGROUND: In a parallel demographic phenomenon, the elderly and obese populations will become a larger part of our population and surgical practices. The elderly obese surgical risk profile is not clearly defined, although studies have confirmed their independent negative effect on surgical outcomes. Benign foregut surgery is a relatively common complex procedure performed on this demographic and warrants deeper investigation into outcomes. We investigate the synergistic effect of age and body mass index (BMI) on the outcomes of benign foregut surgery. METHODS: Data from National Surgical Quality Improvement Program were collected for all patients undergoing foregut surgery from 2005 to 2012. Subjects were over 18 years of age and 16 BMI. Primary and secondary outcomes were 30-day mortality and overall 30-day morbidity, respectfully. Binary logistic regression models were used to assess independent and interactive effects of age and BMI. RESULTS: A total of 19,547 patients had an average age and BMI of 57 and 29.7, respectively. Sample 30-day mortality was 0.32 %. Every 10-year age increase led to a 46 % increased odds of mortality. BMI showed a bimodal distribution with underweight and morbidly obese patients having increased mortality. The effect of BMI only became apparent with increasing age. CONCLUSIONS: Both age and BMI are independent predictors of mortality; only older patients experienced the bimodal BMI effect. Therefore, increasing age and BMI have a synergistic effect on outcomes after foregut operations. PMID- 26377068 TI - Targeted exome sequencing reveals novel USH2A mutations in Chinese patients with simplex Usher syndrome. AB - BACKGROUND: Usher syndrome (USH) is an autosomal recessive disorder characterized by hearing impairment and vision dysfunction due to retinitis pigmentosa. Phenotypic and genetic heterogeneities of this disease make it impractical to obtain a genetic diagnosis by conventional Sanger sequencing. METHODS: In this study, we applied a next-generation sequencing approach to detect genetic abnormalities in patients with USH. Two unrelated Chinese families were recruited, consisting of two USH afflicted patients and four unaffected relatives. We selected 199 genes related to inherited retinal diseases as targets for deep exome sequencing. Through systematic data analysis using an established bioinformatics pipeline, all variants that passed filter criteria were validated by Sanger sequencing and co-segregation analysis. RESULTS: A homozygous frameshift mutation (c.4382delA, p.T1462Lfs*2) was revealed in exon20 of gene USH2A in the F1 family. Two compound heterozygous mutations, IVS47 + 1G > A and c.13156A > T (p.I4386F), located in intron 48 and exon 63 respectively, of USH2A, were identified as causative mutations for the F2 family. Of note, the missense mutation c.13156A > T has not been reported so far. CONCLUSION: In conclusion, targeted exome sequencing precisely and rapidly identified the genetic defects in two Chinese USH families and this technique can be applied as a routine examination for these disorders with significant clinical and genetic heterogeneity. PMID- 26377067 TI - Faecal microbiota characterisation of horses using 16 rdna barcoded pyrosequencing, and carriage rate of clostridium difficile at hospital admission. AB - BACKGROUND: The equine faecal microbiota is very complex and remains largely unknown, while interspecies interactions have an important contribution to animal health. Clostridium difficile has been identified as an important cause of diarrhoea in horses. This study provides further information on the nature of the bacterial communities present in horses developing an episode of diarrhoea. The prevalence of C. difficile in hospitalised horses at the time of admission is also reported. RESULTS: Bacterial diversity of the gut microbiota in diarrhoea is lower than that in non-diarrhoeic horses in terms of species richness (p-value <0.002) and in population evenness (p-value: 0.02). Statistical differences for Actinobacillus, Porphyromonas, RC9 group, Roseburia and Ruminococcaceae were revealed. Fusobacteria was found in horses with diarrhoea but not in any of the horses with non-diarrheic faeces. In contrast, Akkermansia was among the three predominant taxa in all of the horses studied. The overall prevalence of C. difficile in the total samples of hospitalised horses at admission was 3.7 % (5/134), with five different PCR-ribotypes identified, including PCR-ribotype 014. Two colonised horses displayed a decreased bacterial species richness compared to the remaining subjects studied, which shared the same Bacteroides genus. However, none of the positive animals had diarrhoea at the moment of sampling. CONCLUSIONS: The abundance of some taxa in the faecal microbiota of diarrhoeic horses can be a result of microbiome dysbiosis, and therefore a cause of intestinal disease, or some of these taxa may act as equine enteric pathogens. Clostridium difficile colonisation seems to be transient in all of the horses studied, without overgrowth to trigger infection. A large proportion of the sequences were unclassified, showing the complexity of horses' faecal microbiota. PMID- 26377069 TI - Spirochaeta odontotermitis sp. nov., an obligately anaerobic, cellulolytic, halotolerant, alkaliphilic spirochaete isolated from the termite Odontotermes obesus (Rambur) gut. AB - A Gram-stain-negative spirochaete (strain JC202T) was isolated from the gut of the termite Odontotermes obesus (Rambur) from Rann of Kutch, Gujarat, India. This strain was obligately anaerobic, mesophilic, halotolerant and required alkaline conditions for growth. Strain JC202T was resistant to rifampicin and kanamycin, but sensitive to gentamicin, tetracycline, ampicillin and chloramphenicol. Strain JC202T possessed phosphatidylglycerol, diphosphatidylglycerol, glycolipid and six unidentified lipids. C18 : 1omega7c was the predominant cellular fatty acid with significant proportions of C16 : 0, C18 : 1omega9c, C14 : 0, C18 : 0, C16 : 1omega5c, C18 : 1omega5c and C20 : 1omega9c. The DNA G+C content of strain JC202T was 59 mol%. Based on 16S rRNA gene sequence analysis, strain JC202T is considered to belong to the genus Spirochaeta with Spirochaeta sphaeroplastigenens JC133T (100 % similarity), Spirochaeta alkalica Z-7491T (99.92 %), Spirochaeta americana ATCC BAA-392T (99.47 %) and other members of the genus Spirochaeta ( < 93.83 %) as the closest phylogenetic neighbours. However, mean DNA-DNA hydridization values between strain JC202T and S. sphaeroplastigenens JC133T, S. alkalica DSM 8900T ( = Z-7491T) and S. americana DSM 14872T ( = ASpG1T) were 55 +/- 2, 22 +/- 3 and 32 +/- 1 %, respectively. On the basis of physiological, biochemical, chemotaxonomic (including metabolome) and genomic differences from the previously described taxa, strain JC202T is differentiated from other members of the genus Spirochaeta and is considered to represent a novel species, for which the name Spirochaeta odontotermitis sp. nov. is proposed. The type strain is JC202T ( = KCTC 15324T = NBRC 110104T). PMID- 26377071 TI - Variation in habitat use along the freshwater-marine continuum by grey mullet Mugil cephalus at the southern limits of its distribution. AB - In this study, habitat use by Mugil cephalus was investigated in the waters of the west coast of the North Island of New Zealand by analysing microchemical composition of otoliths (laser-ablation inductively coupled plasma mass spectrometry) obtained from individuals from commercial fish stocks and research surveys. Results of this study show that M. cephalus at the southern limits of its distribution display highly flexible migratory behaviour with extensive use of freshwater and brackish habitats, potentially enabling them to maximize foraging opportunities. Mugil cephalus can tolerate a wide range of salinities and can therefore utilize higher productivity areas, such as estuaries and eutrophic riverine lakes. Finally, M. cephalus populations across a range of climates and latitudes appear to differ in the extent to which they utilize freshwater and brackish habitats, possibly with increasing penetration of fresh waters with increasing latitude. PMID- 26377070 TI - Design, implementation and evaluation of a training programme for school teachers in the use of malaria rapid diagnostic tests as part of a basic first aid kit in southern Malawi. AB - BACKGROUND: With increasing levels of enrolment, primary schools present a pragmatic opportunity to improve the access of school children to timely diagnosis and treatment of malaria, increasingly recognised as a major health problem within this age group. The expanded use of malaria rapid diagnostic tests (RDTs) and artemisinin combination therapy (ACT) by community health workers (CHWs) has raised the prospect of whether teachers can provide similar services for school children. We describe and evaluate the training of primary school teachers to use a first aid kit containing malaria RDTs and ACT for the diagnosis and treament of uncomplicated malaria in school children in southern Malawi. METHODS: We outline the development of the intervention as: (1) conception and design, (2) pilot training, (3) final training, and (4) 7-month follow up. The training materials were piloted at a four-day workshop in July 2013 following their design at national stakeholders meetings. The evaluation of the pilot training and materials were assessed in relation to increased knowledge and skill sets using checklist evaluations and questionnaires, the results of which informed the design of a final seven-day training programme held in December 2013. A follow up of trained teachers was carried out in July 2014 following 7 months of routine implementation. A total of 15 teachers were evaluated at four stages: pilot training, two weeks following pilot, final training and seven months following final training. RESULTS: A total of 15 and 92 teachers were trained at the pilot and final training respectively. An average of 93 % of the total steps required to use RDTs were completed correctly at the final training, declining to 87 % after 7 months. All teachers were observed correctly undertaking safe blood collection and handling, accurate RDT interpretation, and correct dispensing of ACT. The most commonly observed errors were a failure to wait 20 minutes before reading the test result, and adding an incorrect volume of buffer to the test cassette. CONCLUSION: Following training, teachers are able to competently use RDTs and ACTs test and treat children at school for uncomplicated malaria safely and accurately. Teachers demonstrate a comparable level of RDT use relative to non-health professional users of RDTs, and sustain this competency over a period of seven months during routine implementation. PMID- 26377072 TI - Using Automated Scoring to Evaluate Written Responses in English and French on a High-Stakes Clinical Competency Examination. AB - We present a framework for technology-enhanced scoring of bilingual clinical decision-making (CDM) questions using an open-source scoring technology and evaluate the strength of the proposed framework using operational data from the Medical Council of Canada Qualifying Examination. Candidates' responses from six write-in CDM questions were used to develop a three-stage-automated scoring framework. In Stage 1, the linguistic features from CDM responses were extracted. In Stage 2, supervised machine learning techniques were employed for developing the scoring models. In Stage 3, responses to six English and French CDM questions were scored using the scoring models from Stage 2. Of the 8,007 English and French CDM responses, 7,643 were accurately scored with an agreement rate of 95.4% between human and computer scoring. This result serves as an improvement of 5.4% when compared with the human inter-rater reliability. Our framework yielded scores similar to those of expert physician markers and could be used for clinical competency assessment. PMID- 26377073 TI - A non-negative matrix factorization method for detecting modules in heterogeneous omics multi-modal data. AB - MOTIVATION: Recent advances in high-throughput omics technologies have enabled biomedical researchers to collect large-scale genomic data. As a consequence, there has been growing interest in developing methods to integrate such data to obtain deeper insights regarding the underlying biological system. A key challenge for integrative studies is the heterogeneity present in the different omics data sources, which makes it difficult to discern the coordinated signal of interest from source-specific noise or extraneous effects. RESULTS: We introduce a novel method of multi-modal data analysis that is designed for heterogeneous data based on non-negative matrix factorization. We provide an algorithm for jointly decomposing the data matrices involved that also includes a sparsity option for high-dimensional settings. The performance of the proposed method is evaluated on synthetic data and on real DNA methylation, gene expression and miRNA expression data from ovarian cancer samples obtained from The Cancer Genome Atlas. The results show the presence of common modules across patient samples linked to cancer-related pathways, as well as previously established ovarian cancer subtypes. AVAILABILITY AND IMPLEMENTATION: The source code repository is publicly available at https://github.com/yangzi4/iNMF. CONTACT: gmichail@umich.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26377074 TI - Total Corneal Astigmatism Measurement Precision. PMID- 26377075 TI - Author Response: Total Corneal Astigmatism Measurement Precision. PMID- 26377076 TI - Reticular Pseudodrusen: A Common Pathogenic Mechanism Affecting the Choroid Bruch's Membrane Complex and Retinal Pigment Epithelium for Different Retinal and Macular Diseases. PMID- 26377077 TI - Author Response: Reticular Pseudodrusen: A Common Pathogenic Mechanism Affecting the Choroid-Bruch's Membrane Complex and Retinal Pigment Epithelium for Different Retinal and Macular Diseases. PMID- 26377078 TI - Transvitreal Retinochoroidal Biopsy Provides a Representative Sample From Choroidal Melanoma for Detection of Chromosome 3 Aberrations. AB - PURPOSE: To compare the status of chromosomes 3 and 8 in 25-gauge transvitreal retinochoroidal (TVRC) biopsy specimens and enucleated eyes in order to evaluate for genetic heterogeneity and the utility of TVRC biopsy to obtain an adequate sampling of the tumor. METHODS: Genetic heterogeneity was evaluated in 27 patients treated at Rigshospitalet between 2009 and 2013. The TVRC biopsy was performed to confirm diagnosis prior to enucleation and was subsequently analyzed using two techniques for chromosomes 1p, 3, 6, and 8: Fluorescence in situ hybridization (FISH) in all patients, and multiplex ligation-dependent probe amplification (MLPA) in 16 patients. Biopsies were compared with histological sections from matched enucleated eyes, which were microdissected following a hexagonal grid and analyzed with MLPA. RESULTS: Twenty-four tumors were available for analysis. The TVRC biopsy identified chromosome 3 aberrations with MLPA in all cases (sensitivity = 100%), while FISH missed two cases (sensitivity = 89%). Conversely, FISH analysis demonstrated polyploidy of chromosome 3 in three additional cases missed by MLPA. Chromosome 8 aberrations were detected in 75% of cases with MLPA and 68% of cases with FISH. Heterogeneity of chromosomes 3 and 8 was shown in 3 (13%) and 11 tumors (46%), respectively, with an increased frequency of genetic aberrations toward the base of the tumor (P = 0.049). The study showed no difference in tumor size between heterogeneous and homogenous melanomas (P = 0.82). CONCLUSIONS: Regardless of genetic heterogeneity, the TVRC biopsy identified all patients with a high risk of developing metastatic disease when a combination of chromosome 3 and 8 status was assessed. PMID- 26377079 TI - Impact of Cationic Amino Acid Transporter 1 on Blood-Retinal Barrier Transport of L-Ornithine. AB - PURPOSE: To elucidate L-ornithine transport at the blood-retinal barrier (BRB). METHODS: Integration plot and retinal uptake index (RUI) were used to investigate the in vivo [3H]L-ornithine transport across the BRB. In vitro transport studies of [3H]L-ornithine were performed with TR-iBRB2 cells and RPE-J cells, the model cells of the inner and outer BRB, respectively. Immunohistochemistry was performed on cationic amino acid transporter 1 (CAT1/SLC7A1). RESULTS: The apparent influx permeability clearance of [3H]L-ornithine was found to be 18. 7 MUL/(min.g retina), and the RUI of [3H]L-ornithine was reduced by L-ornithine and L-arginine, suggesting the blood-to-retina transport of L-ornithine at the BRB. [3H]L-Ornithine uptake by TR-iBRB2 cells showed a time-, temperature- and concentration-dependence with a Michaelis-Menten constant (K(m)) of 33.2 MUM and a nonsaturable uptake rate (Kd) of 2.18 MUL/(min.mg protein). The uptake was Na+ independent, and was inhibited by L-ornithine, L-arginine, and L-lysine, suggesting the involvement of CAT1 in L-ornithine transport at the inner BRB. Immunohistochemistry revealed the luminal and abluminal localization of CAT1 at the inner BRB, and at the basal localization at the outer BRB. Retinal pigment epithelium-J cells showed that the basal-to-cell (B-to-C) uptake of [3H]L ornithine was greater than that of the apical-to-cell (A-to-C) uptake, and the B to-C transport was inhibited by unlabeled L-ornithine, suggesting the involvement of CAT1 in the blood-to-cell transport of L-ornithine across the basal membrane at the outer BRB. CONCLUSIONS: These suggest the involvement of CAT1 in L ornithine transport at the luminal and abluminal sides of the inner BRB and the basal side of the outer BRB. PMID- 26377080 TI - Alpha2-Adrenergic-Agonist Brimonidine Stimulates Negative Feedback and Attenuates Injury-Induced Phospho-ERK and Dedifferentiation of Chicken Muller Cells. AB - PURPOSE: Retinal injury induces Muller cell dedifferentiation by activating extracellular signal-regulated kinase (ERK) signaling. Stimulation of alpha2 adrenergic receptors protects against injury but also activates ERK in Muller cells. The purpose of this work was to study the effect of alpha2-adrenergic signaling on injury-induced ERK and Muller cell dedifferentiation. We tested the hypothesis that alpha2-stimulation triggers negative feedback regulation of the injury-induced ERK pathway that attenuates Muller cell dedifferentiation. METHODS: Chicken retina injured by N-methyl-D-aspartate and cultured primary Muller cells were stimulated by the alpha2-adrenergic agonist brimonidine. Immunostaining, quantitative RT-PCR, and Western blot techniques in combination with receptor blockers were used for analysis of the cellular responses. RESULTS: Alpha2-adrenergic receptor stimulation attenuated injury-induced ERK activation and dedifferentiation of Muller cells as seen by decreased phospho-ERK, expression of transitin, and retinal progenitor cell genes. The attenuation was concomitant with a synergistic upregulation of several negative ERK-signal feedback regulators including ERK-phosphatases, Raf1-, and growth factor receptor binding proteins. The results were also seen in cultures of primary Muller cells. CONCLUSIONS: Alpha2-adrenergic signaling on Muller cells elicits an intracellular attenuation of the injury response that comprises negative ERK-signaling feedback leading to attenuated Muller cell dedifferentiation. The implications of this study are that adrenergic stress signals may directly modulate glial function in retina and that alpha2-adrenergic receptor pharmacology may be used to control glial injury response. PMID- 26377081 TI - Predicting Progression of ABCA4-Associated Retinal Degenerations Based on Longitudinal Measurements of the Leading Disease Front. AB - PURPOSE: To evaluate the progression of the earliest stage of disease in ABCA4 associated retinal degenerations (RDs). METHODS: Near-infrared excited reduced illuminance autofluorescence imaging was acquired across the retina up to 80 degrees eccentricity in 44 patients with two ABCA4 alleles. The eccentricity of the leading disease front (LDF) corresponding to the earliest stage of disease was measured along the four meridians. A mathematical model describing the expansion of the LDF was developed based on 6 years of longitudinal follow-up. RESULTS: The extent of LDF along the superior, inferior, and temporal meridians showed a wide spectrum from 3.5 to 70 degrees. In patients with longitudinal data, the average centrifugal expansion rate was 2 degrees per year. The nasal extent of LDF between the fovea and ONH ranged from 4.3 to 16.5 degrees and expanded at 0.35 degrees per year. The extent of LDF beyond ONH ranged from 19 to 75 degrees and expanded on average at 2 degrees per year. A mathematical model fit well to the longitudinal data describing the expansion of the LDF. CONCLUSIONS: The eccentricity of the LDF in ABCA4-RD shows a continuum from parafovea to far periphery along all four meridians consistent with a wide spectrum of severity observed clinically. The model of progression may provide a quantitative prediction of the LDF expansion based on the age and eccentricity of the LDF at a baseline visit, and thus contribute significantly to the enrollment of candidates appropriate for clinical trials planning specific interventions, efficacy outcomes, and durations. PMID- 26377082 TI - A Novel Model of Metastatic Conjunctival Melanoma in Immune-Competent Mice. AB - PURPOSE: Conjunctival melanoma (CM) is an ocular surface tumor that can lead to fatal metastases. Patients developing, tumor-associated lymphangiogenesis have a significantly increased risk of metastatic disease, because tumor spread primarily occurs via lymphatic vessels to the draining lymph node. Here, we describe a novel immune-competent mouse model of CM that displays tumor associated lymphangiogenesis with development of metastatic tumors. METHODS: C57BL/6N mice received C57BL/6N-derived dermal melanoma cells (hepatocyte growth factor [HGF] cyclin dependent kinase-4 [Cdk4]+) or B16F10 via subconjunctival injection. A clinical score quantified primary tumor growth and metastases were identified by macroscopic examination of the draining lymph nodes, lung, and spleen. Confirmation of tumors and metastases was achieved by immunohistochemical staining for markers of pigmented cells (tyrosinase related protein-2 [TRP2]) and S-100, and of cell proliferation (Ki67). The intra- and peritumoral CD31+ blood and lymphatic vessel endothelium hyaluronan receptor-1 (LYVE-1)+ lymphatic vessels were quantified immunohistochemically. RESULTS: All mice rapidly developed aggressive TRP2+, S100+, and Ki67+ CM. Metastatic tumors were found in the lymph node (9%) and lung (6%) of HGF-Cdk4(R24C)-treated mice and in the spleen (8%) and lung (17%) of B16F10-treated mice. The amount of peri- and intratumoral blood vessels was significantly increased compared with lymphatic vessels. CONCLUSIONS: This CM model in immune-competent animals offers new possibilities to study the pathobiology of tumor growth, invasion, and mechanisms of metastatic tumor spread, and provides a robust model to explore new immune based and antilymphangiogenic treatment modalities of this malignancy. PMID- 26377083 TI - Substrate Elastic Modulus Regulates the Morphology, Focal Adhesions, and alpha Smooth Muscle Actin Expression of Retinal Muller Cells. AB - PURPOSE: The stiffness of the extracellular matrix has been shown to regulate cell adhesion, migration, and transdifferentiation in fibrotic processes. Retinal Muller cells have been shown to be mechanosensitive; they are involved in fibrotic vitreoretinal diseases. Since fibrosis increases the rigidity of the extracellular matrix, our aim was to develop an in vitro model for studying Muller cell morphology and differentiation state in relation to matrix stiffness. METHODS: A spontaneously immortalized human Muller cell line (MIO-M1) was cultured on type I collagen-coated polyacrylamide gels with Young's moduli ranging from 2 to 92 kPa. Cell surface area, focal adhesion, and the expression and morphology of alpha-smooth muscle actin induced by transforming growth factor beta (TGF-beta [10 ng/mL for 48 hours]) were analyzed by immunocytology. The images were documented by using fluorescence microscopy and confocal scanning laser microscopy. RESULTS: MIO-M1 cells cultured on stiff substrates exhibited a significant increase in cell surface area, stress fiber, and mature focal adhesion formation. Furthermore, Muller cells treated with TGF-beta1 and TGF beta2 and cultured on stiff substrates showed an increased incorporation of alpha smooth muscle actin into stress fibers when compared to those grown on soft surfaces. CONCLUSIONS: Compliance of the surrounding matrix seems to influence the morphology and contraction of retinal Muller cells in fibrotic conditions. Development of an in vitro model simulating both the normally compliant retinal tissue and the rigid retinal fibrotic tissue helps fill the gap between the results of petri-dish cell culture with rigid surfaces and in vivo findings. PMID- 26377084 TI - Immunotherapy of Breast Cancer. AB - Cancer immunoediting is the process by which the immune system protects the host from tumor development and guides the somatic evolution of tumors by eliminating highly immunogenic tumor cells. A fundamental dogma of tumor immunology and of cancer immunosurveillance in particular is that cancer cells express antigens that differentiate them from their nontransformed counterparts. Molecular studies clearly show that these antigens were often products of mutated cellular genes, aberrantly expressed normal genes, or genes encoding viral proteins. There is a strict correlation between genetic instability and the immune landscape of a breast cancer. Mutational heterogeneity in breast cancer is associated with new cancer-associated genes and new cancer antigens. Frequencies of somatic mutations or mutational burden can be related to the immunogenicity of breast cancer. We believe that molecular subtypes of breast cancer that are triple negative, luminal B-like or HER2-positive have a high mutational burden and can be considered immunogenic. The increasing knowledge of the immune system's capacity to not only recognize and destroy cancer, but also to shape cancer immunogenicity will develop more informed attempts to control cancer via immunological approaches. To be effective in breast cancer, immunotherapies will have to increase the quality or quantity of immune effector cells, reveal additional protective tumor antigens, and/or eliminate cancer-induced immunosuppressive mechanisms. Multiple immunotherapy approaches are under investigation in patients with breast cancer. These include vaccine approaches to elicit strong specific immune responses to tumor antigens such as WT-1, HER2 and NY-ESO-1, approaches involving adoptive transfer of in vitro-expanded, naturally arising or genetically engineered tumor-specific lymphocytes, therapeutic administration of monoclonal antibodies to target and eliminate tumor cells, and approaches that inhibit or destroy the molecular or cellular mediators of cancer-induced immunosuppression, such as CTLA-4, PD-1 or Treg cells. Here we provide a concise and comprehensive review on the role and utility of promising immunotherapeutics for the treatment of patients with breast cancer. PMID- 26377086 TI - Risk of endometrial polyps in women with endometriosis: a meta-analysis. AB - BACKGROUND: Endometrial polyps (EP) and endometriosis are both estrogen-dependent overgrowths of the endometrium. Several studies have shown a higher frequency of EP in endometriosis patients when compared with women without endometriosis. Therefore, we performed a meta-analysis to investigate the risk of EP in women with endometriosis. METHODS: This meta-analysis searched for articles published between 1964 and 2014 in PubMed, Embase, and Cochrane Library, as well as in Chinese databases, including CNKI, VIP and Wanfang, regarding the association between endometriosis and EP. Nine cohort studies and one case-control study including 2896 women were included in this meta-analysis. The EP risk was evaluated using relative risk (RR) with a 95% confidence interval (CI). Heterogeneity, small study effect and publication bias were assessed using Higgins I(2), sensitivity analysis and funnel plots, respectively. RESULTS: The risk of EP increased in women with endometriosis compared with those without endometriosis (the pooled RR, 2.81; 95% CI, 2.48-3.18). No significant heterogeneity, small study effect or publication bias was found. The risk of EP slightly increased in women with endometriosis at stages 2-4 compared with those at stage 1 (Pooled effect size: stage 2 versus stage 1, RR, 1.22, 95% CI, 1.04 - 1.42; stage 3 versus stage 1, RR, 1.23, 95% CI, 1.06-1.42; stage 4 versus stage 1, RR, 1.29, 95% CI, 1.11-1.51; stages 2-4 versus stage 1, RR, 1.24, 95% CI, 1.10 1.40); however, no significantly different risk of EP in women with endometriosis existed between the other stages. CONCLUSION: The results suggest that it is important to identify whether patients with endometriosis also have EP and then remove any coexisting EP via hysteroscopy, especially for infertile patients. This process will be clinically helpful to treat endometriosis-related infertility in patients with endometriosis, especially for those with endometriosis that is more serious than stage 1. PMID- 26377085 TI - 'Medusa-head ataxia': the expanding spectrum of Purkinje cell antibodies in autoimmune cerebellar ataxia. Part 1: Anti-mGluR1, anti-Homer-3, anti-Sj/ITPR1 and anti-CARP VIII. AB - Serological testing for anti-neural autoantibodies is important in patients presenting with idiopathic cerebellar ataxia, since these autoantibodies may indicate cancer, determine treatment and predict prognosis. While some of them target nuclear antigens present in all or most CNS neurons (e.g. anti-Hu, anti Ri), others more specifically target antigens present in the cytoplasm or plasma membrane of Purkinje cells (PC). In this series of articles, we provide a detailed review of the clinical and paraclinical features, oncological, therapeutic and prognostic implications, pathogenetic relevance, and differential laboratory diagnosis of the 12 most common PC autoantibodies (often referred to as 'Medusa-head antibodies' due to their characteristic somatodendritic binding pattern when tested by immunohistochemistry). To assist immunologists and neurologists in diagnosing these disorders, typical high-resolution immunohistochemical images of all 12 reactivities are presented, diagnostic pitfalls discussed and all currently available assays reviewed. Of note, most of these antibodies target antigens involved in the mGluR1/calcium pathway essential for PC function and survival. Many of the antigens also play a role in spinocerebellar ataxia. Part 1 focuses on anti-metabotropic glutamate receptor 1 , anti-Homer protein homolog 3-, anti-Sj/inositol 1,4,5-trisphosphate receptor- and anti-carbonic anhydrase-related protein VIII-associated autoimmune cerebellar ataxia (ACA); part 2 covers anti-protein kinase C gamma-, anti-glutamate receptor delta-2-, anti-Ca/RhoGTPase-activating protein 26- and anti-voltage-gated calcium channel-associated ACA; and part 3 reviews the current knowledge on anti-Tr/delta notch-like epidermal growth factor-related receptor-, anti-Nb/AP3B2-, anti Yo/cerebellar degeneration-related protein 2- and Purkinje cell antibody 2 associated ACA, discusses differential diagnostic aspects and provides a summary and outlook. PMID- 26377087 TI - Activation of Src-dependent Smad3 signaling mediates the neutrophilic inflammation and oxidative stress in hyperoxia-augmented ventilator-induced lung injury. AB - BACKGROUND: Mechanical ventilation and concomitant administration of hyperoxia in patients with acute respiratory distress syndrome can damage the alveolar epithelial and capillary endothelial barrier by producing inflammatory cytokines and reactive oxygen species. The Src tyrosine kinase and Smad3 are crucial inflammatory regulators used for ventilator-induced lung injury (VILI). The mechanisms regulating interactions between high-tidal-volume mechanical ventilation, hyperoxia, and acute lung injury (ALI) are unclear. We hypothesized that high-tidal-volume mechanical stretches and hyperoxia augment lung inflammation through upregulation of the Src and Smad3 pathways. METHODS: Wild type or Src-deficient C57BL/6 mice, aged between 6 and 8 weeks, were exposed to high-tidal-volume (30 mL/kg) ventilation with room air or hyperoxia for 1-4 h after 2-mg/kg Smad3 inhibitor (SIS3) administration. Nonventilated mice were used as control subjects. RESULTS: We observed that the addition of hyperoxia to high tidal-volume mechanical ventilation further induced microvascular permeability, neutrophil infiltration, macrophage inflammatory protein-2 and matrix metalloproteinase-9 (MMP-9) production, malondialdehyde, nicotinamide adenine dinucleotide phosphate oxidase activity, MMP-9 mRNA expression, hypoxemia, and Src and Smad3 activation (P < 0.05). Hyperoxia-induced augmentation of VILI was attenuated in Src-deficient mice and mice with pharmacological inhibition of Smad3 activity by SIS3 (P < 0.05). Mechanical ventilation of Src-deficient mice with hyperoxia further reduced the activation of Smad3. CONCLUSIONS: Our data suggest that hyperoxia-increased high-tidal-volume ventilation-induced ALI partially depends on the Src and Smad3 pathways. PMID- 26377090 TI - Corrigendum. PMID- 26377088 TI - Gene activity in primary T cells infected with HIV89.6: intron retention and induction of genomic repeats. AB - BACKGROUND: HIV infection has been reported to alter cellular gene activity, but published studies have commonly assayed transformed cell lines and lab-adapted HIV strains, yielding inconsistent results. Here we carried out a deep RNA-Seq analysis of primary human T cells infected with the low passage HIV isolate HIV89.6. RESULTS: Seventeen percent of cellular genes showed altered activity 48 h after infection. In a meta-analysis including four other studies, our data differed from studies of HIV infection in cell lines but showed more parallels with infections of primary cells. We found a global trend toward retention of introns after infection, suggestive of a novel cellular response to infection. HIV89.6 infection was also associated with activation of several human endogenous retroviruses (HERVs) and retrotransposons, of interest as possible novel antigens that could serve as vaccine targets. The most highly activated group of HERVs was a subset of the ERV-9. Analysis showed that activation was associated with a particular variant of ERV-9 long terminal repeats that contains an indel near the U3-R border. These data also allowed quantification of >70 splice forms of the HIV89.6 RNA and specified the main types of chimeric HIV89.6-host RNAs. Comparison to over 100,000 integration site sequences from the same infected cell populations allowed quantification of authentic versus artifactual chimeric reads, showing that 5' read-in, splicing out of HIV89.6 from the D4 donor and 3' read-through were the most common HIV89.6-host cell chimeric RNA forms. CONCLUSIONS: Analysis of RNA abundance after infection of primary T cells with the low passage HIV89.6 isolate disclosed multiple novel features of HIV-host interactions, notably intron retention and induction of transcription of retrotransposons and endogenous retroviruses. PMID- 26377089 TI - Why the Central Dogma: on the nature of the great biological exclusion principle. AB - The Central Dogma of molecular biology posits that transfer of information from proteins back to nucleic acids does not occur in biological systems. I argue that the impossibility of reverse translation is indeed a major, physical exclusion principle that emerges due to the transition from the digital information carriers, nucleic acids, to analog information carriers, proteins, which involves irreversible suppression of the digital information. PMID- 26377091 TI - Experience and lessons from health impact assessment for human rights impact assessment. AB - As globalisation has opened remote parts of the world to foreign investment, global leaders at the United Nations and beyond have called on multinational companies to foresee and mitigate negative impacts on the communities surrounding their overseas operations. This movement towards corporate impact assessment began with a push for environmental and social inquiries. It has been followed by demands for more detailed assessments, including health and human rights. In the policy world the two have been joined as a right-to-health impact assessment. In the corporate world, the right-to-health approach fulfils neither managers' need to comprehensively understand impacts of a project, nor rightsholders' need to know that the full suite of their human rights will be safe from violation. Despite the limitations of a right-to-health tool for companies, integration of health into human rights provides numerous potential benefits to companies and the communities they affect. Here, a detailed health analysis through the human rights lens is carried out, drawing on a case study from the United Republic of Tanzania. This paper examines the positive and negative health and human rights impacts of a corporate operation in a low-income setting, as viewed through the human rights lens, considering observations on the added value of the approach. It explores the relationship between health impact assessment (HIA) and human rights impact assessment (HRIA). First, it considers the ways in which HIA, as a study directly concerned with human welfare, is a more appropriate guide than environmental or social impact assessment for evaluating human rights impacts. Second, it considers the contributions HRIA can make to HIA, by viewing determinants of health not as direct versus indirect, but as interrelated. PMID- 26377092 TI - Dosimetric comparison of carbon ion radiotherapy and stereotactic body radiotherapy with photon beams for the treatment of hepatocellular carcinoma. AB - BACKGROUND: The purpose of this study was to compare carbon ion radiotherapy (C ion RT) and stereotactic radiotherapy (SBRT) with photon beams for the treatment of hepatocellular carcinoma (HCC), specifically with regard to the dose volume parameters for target coverage and normal tissue sparing. METHODS: Data of 10 patients who were treated using C-ion RT with a total dose of 60 Gy(RBE) in four fractions were used. The virtual plan of SBRT was simulated on the treatment planning computed tomography images of C-ion RT. Dose volume parameters such as minimum dose covering 90% of the planning target volume (PTV D90), homogeneity index (HI), conformity index (CI), mean liver dose (MLD), volume of the liver receiving 5 to 60 Gy (V5-60), and max point dose (Dmax) of gastrointestinal (GI) tract were calculated from both treatment plans. RESULTS: The PTV D90 was 59.6 +/ 0.2 Gy(RBE) in C-ion RT, as compared to 56.6 +/- 0.3 Gy in SBRT (p < 0.05). HI and CI were 1.19 +/- 0.03 and 0.79 +/- 0.06, respectively in C-ion RT, as compared to 1.21 +/- 0.01 and 0.37 +/- 0.02, respectively in SBRT. Only CI showed a significant difference between two modalities. Mean liver dose was 8.1 +/- 1.4 Gy(RBE) in C-ion RT, as compared to 16.1 +/- 2.5 Gy in SBRT (p < 0.05). V5 to V50 of liver were higher in SBRT than C-ion RT and significant differences were observed for V5, V10 and V20. Dmax of the GI tract was higher in SBRT than C-ion RT, but did not show a significantly difference. CONCLUSIONS: C-ion RT provides an advantage in both target conformity and normal liver sparing compared with SBRT. PMID- 26377094 TI - Association between anthropometry-based nutritional status and malaria: a systematic review of observational studies. AB - BACKGROUND: Multiple studies in various parts of the world have analysed the association of nutritional status on malaria using anthropometric measures, but results differ due to the heterogeneity of the study population, species of the parasite, and other factors involved in the host and parasite relationship. The aim of this study was to perform a systematic review on the inter-relationship of nutritional status based on anthropometry and malarial infection. METHODS: Two independent reviewers accessed the MEDLINE and LILACS databases using the same search terms related to malaria and anthropometry. Prospective studies associating anthropometry and malaria (incidence or severity) were selected. References from the included studies and reviews were used to increase the review sensitivity. Data were extracted using a standardized form and the quality of the prospective studies was assessed. Selected articles were grouped based on exposures and outcomes. RESULTS: The search identified a total of 1688 studies: 1629 from MEDLINE and 59 from LILACS. A total of 23 met the inclusion criteria. Five additional studies were detected by reading the references of the 23 included studies and reviews, totaling 28 studies included. The mean sample size was 662.1 people, ranging from 57 to 5620. The mean follow-up was 365.8 days, ranging from 14 days to 1 year and 9 months, and nine studies did not report the follow-up period. Prospective studies assessing the relationship between malaria and malnutrition were mostly carried out in Africa. Of the 20 studies with malarial outcomes, fifteen had high and five had average quality, with an average score of 80.5 %. Most anthropometric parameters had no association with malaria incidence (47/52; 90.4 %) or parasite density (20/25; 80 %). However, the impact of malnutrition was noted in malaria mortality and severity (7/17; 41.2 %). Regarding the effects of malaria on malnutrition, malaria was associated with very few anthropometric parameters (8/39; 20.6 %). CONCLUSIONS: This systematic review found that most of the evidence associating malaria and malnutrition comes from P. falciparum endemic areas, with a significant heterogeneity in studies' design. Apparently malnutrition has not a great impact on malaria morbidity, but could have a negative impact on malaria mortality and severity. Most studies show no association between malaria and subsequent malnutrition in P. falciparum areas. In Plasmodium vivax endemic areas, malaria was associated with malnutrition in children. A discussion among experts in the field is needed to standardize future studies to increase external validity and accuracy. PMID- 26377095 TI - Shorter survival rate in varus-aligned knees after total knee arthroplasty. AB - PURPOSE: One long-held tenet of total knee arthroplasty (TKA) is that post operative neutral limb alignment promotes implant durability. Recently, the concept of generic safe zone (0 degrees +/- 3 degrees ) has been challenged. This meta-analysis aimed to evaluate whether neutral alignment was superior to malalignment in long-term survival of TKAs. METHODS: The MEDLINE, Embase, Cochrane Library, China National Knowledge Infrastructure, Wan Fang Chinese Periodical, Google and reference lists of all the included studies were searched. Of the 1512 studies initially identified, ten met the eligibility criteria, including eight case-control studies and two cohort trials. Relative risks of implant failure were compared between post-operative neutrally aligned and malaligned knees. RESULTS: Post-operative malalignment showed higher failure rate of knee implants compared with neutral alignment (95 % CI 1.00-1.88, P = 0.05). Failure rate in knees with varus alignment was significantly higher than with neutral alignment (95 % CI 1.07-2.55, P = 0.02). There was no significant difference in the likelihood of implant failure between knees with valgus and neutral alignment (95 % CI 0.78-2.41, n.s.). No significant difference of failure rate was noted between neutral alignment and malalignment for fixed-bearing prothesis (95 % CI 0.94-1.95, n.s.) or rotating-platform prothesis (95 % CI 0.75 2.73, n.s.). There was no significant difference of failure rate between knees with neutral alignment and malalignment for studies with a mean follow-up of more than 10 years (95 % CI 0.81-2.01, n.s.) or studies using long-leg weight-bearing radiographs (95 % CI 0.79-1.79, n.s.). CONCLUSIONS: Post-operative varus alignment results in shorter survival rate after TKA. Not only neutral limb alignment but also the valgus alignment promotes implant durability. Neutral or valgus alignment rather than varus alignment is essential to achieve long-term survival of TKAs and patient satisfaction. LEVEL OF EVIDENCE: III. PMID- 26377096 TI - Sectioning the anterolateral ligament did not increase tibiofemoral translation or rotation in an ACL-deficient cadaveric model. AB - PURPOSE: The anterolateral ligament (ALL) has been proposed as a possible extra articular stabiliser of the knee. Injury to the ALL may result in residual instability following surgical reconstruction of a ruptured anterior cruciate ligament (ACL). Few studies have evaluated the biomechanical role of the ALL. The purpose of this study was to investigate whether sectioning the ALL would have an influence on tibiofemoral translation or rotation during the anterior drawer, Lachman, pivot shift, external rotation, and internal rotation tests in an ACL deficient knee. METHODS: Only whole-body specimens having an ALL were included in this study. Lachman, anterior drawer, external rotation, and internal rotation tests were performed manually. Pivot shift test was done using a mechanised pivot shifter. The amount of tibiofemoral translation and rotation was recorded by a navigation system. Each specimen was tested in its native state, after sectioning the ACL, and after combined sectioning of the ACL and the ALL. RESULTS: In six out of 14 cadaveric knees, an ALL could be identified. The ACL-deficient knee had significantly more tibiofemoral translation and rotation compared to the native knee (P < 0.05). However, no changes in the magnitudes of translation or rotation were seen after subsequent sectioning of the ALL compared to the ACL-deficient knee (P > 0.05). CONCLUSION: Adding an ALL lesion in an ACL-deficient knee did not increase tibiofemoral instability in this cadaveric model. It remains unclear whether injury to the ALL would result in substantial knee instability in the setting of ACL injury in vivo. Further research is warranted to fully elucidate the role of the ALL during knee kinematics and to determine in which scenarios ALL repair would be warranted. Understanding the function of the ALL may improve the current treatment strategies for ACL ruptures. PMID- 26377097 TI - Predictors of functional outcomes and recurrent shoulder instability after arthroscopic anterior stabilization. AB - PURPOSE: To investigate what factors might predict the results of arthroscopic stabilization for anterior shoulder instability. METHODS: One hundred and forty three patients averaging 25 (15-58) years with traumatic anterior shoulder instability who underwent arthroscopic stabilization were reviewed at a median follow-up of 81 (24-172) months. Sixty-two (56.4 %) individuals were involved in contact sport activities, and there were 40 (30 %) patients who had only one dislocation prior to having surgery. Rowe score was measured preoperatively and at follow-up. RESULTS: Thirty-three (23.1 %) patients experienced recurrent instability 12 (1-120) months after surgery, and 15 of those underwent further surgery. There was a statistically significant lower risk of failure (p = 0.027) for patients who had a surgical procedure after only one episode of shoulder dislocation. Patients treated after the second or further episode of shoulder dislocation exhibited a mean odds ratio for failure of 3.8 (95 % confidence interval 1.2-11.6, p = 0.044) with regard to first-time dislocators. The Rowe score significantly improved from a preoperative value of 25 (5-55) to a postoperative value of 100 (40-100) (p < 0.001). A significantly higher postoperative Rowe score was found in patients older than 24 years of age at the operation (p = 0.011) and in patients with less than eight dislocations prior to surgery (p = 0.05). CONCLUSIONS: These results suggest that better functional results following arthroscopic stabilization can be expected in patients over 24 years of age and in those with a fewer number of dislocations preoperatively. A lower rate of recurrence can be expected if the patient undergoes surgery after the first episode of dislocation. LEVEL OF EVIDENCE: Prognostic study, Level II. PMID- 26377098 TI - Speech changes after coordinative training in patients with cerebellar ataxia: a pilot study. AB - Although rehabilitative training is a necessary adjunct in the management of gait ataxia, it remains unknown whether the possible beneficial effect of intensive coordinative training may translate to activities of daily living, which are closely connected with postural alignment. The aim of the present study was to examine the effectiveness of a 2-week intensive coordinative motor training on speech production. Speech and motor performances in a cohort of ten individuals with cerebellar degeneration were examined three times; before the introduction of training, directly and 4 weeks after the last training session. Each patient was instructed to perform a speaking task of fast syllable repetition and monologue. Objective acoustic analyses were used to investigate six key aspects of speech production disturbed in ataxic dysarthria including accuracy of consonant articulation, accuracy of vowel articulation, irregular alternating motion rates, prolonged phonemes, slow alternating motion rates and inappropriate segmentation. We found that coordinative training had a mild beneficial effect on speech in cerebellar patients. Immediately after the last training session, slight speech improvements were evident in all ten patients. Furthermore, follow up assessment performed 4 weeks later revealed that 90 % of the patients showed better speech performance than before initiation of the therapy. The present study supports evidence that the intensive rehabilitative training may positively affect fine-motor movements such as speech in patients with cerebellar ataxia. PMID- 26377099 TI - Genetic variations in genes of metabolic enzymes predict postoperational prognosis of patients with colorectal cancer. AB - BACKGROUND: Genetic alterations in tricarboxylic acid (TCA) cycle metabolic enzymes were recently linked to various cancers. However, the associations of single nucleotide polymorphisms (SNPs) in genes of these enzymes have not been well studied. METHODS: We genotyped 16 SNPs from 7 genes encoding TCA cycle metabolic enzymes in 697 colorectal carcinoma (CRC) patients receiving surgical resection and analyzed their associations with clinical outcomes by multivariate Cox proportional hazard model. Then, the significant results were validated in another cohort of 256 CRC patients. RESULTS: We identified 4 SNPs in 2 genes had significant associations with CRC death risk and 5 SNPs in 3 genes had significant associations with CRC recurrence risk. Similar significant results were confirmed for rs4131826 in SDHC gene, rs544184 in SDHD gene and rs12071124 in FH gene in a validation cohort. Further analysis indicated that unfavorable genotypes exhibited a significant cumulative effect on overall and recurrence free survival in a dose-dependent manner. Moreover, survival tree analysis indicated that SNP rs4131826 in SDHC gene and SNP rs12071124 in FH gene were the primary factors contributing to the different overall survival time and recurrence-free survival time of CRC patients, respectively. Immunohistochemical analysis further validated the effect of rs4131826 and rs544184 on expression of SDHC and SDHD in tissue samples. CONCLUSIONS: Our study suggests that SNPs in TCA cycle metabolic enzymes might be significantly associated with clinical outcomes in Chinese population diagnosed with CRC. Further functional and validated studies are warranted to expend our results to clinical utility. PMID- 26377101 TI - [Erratum to: Effect of transparent yellow and orange colored contact lenses on color discrimination in the yellow color range]. PMID- 26377100 TI - High Overweight and Obesity in Fontan Patients: A 20-Year History. AB - The prevalence of obesity in long-term survivors with complex congenital heart disease may be increasing, and little is known about the timing and onset of weight gain and growth patterns in these high-risk patients. Prevalence rates of overweight/obesity and longitudinal changes in body mass index (BMI) with age were determined in 606 patients with Fontan circulation seen at a tertiary care cardiology center from 1992 to 2012. The number of clinic encounters (n) was stratified by age group (n = 401, 2-5 years; n = 333, 6-11 years; n = 217, 12-19 years; and n = 129, >20 years). Among adults, 39% were overweight/obese at last clinic visit; 22% overweight, and 17% obese. Childhood anthropometric data were available for 82 adults, of which 15% (n = 12/82) were overweight/obese in childhood. The likelihood of being overweight/obese as an adult was three times higher if there was a BMI >= 85th percentile in childhood (CI 2.1-4.5, P < 0.01). Overweight/obesity in adulthood was associated with lower heart failure rates (4 vs. 19%, P = 0.03). Pediatric rates of overweight/obesity were comparable to national data (NHANES 2011-2012) in every age group: at 2-5 years, (25 vs. 23%), 6-11 years (26 vs. 34%), and 12-19 years (15 vs. 35%). Systolic blood pressure was higher in overweight/obese children as young as 2-5 years of age. Childhood and adult survivors with Fontan circulation have high rates of overweight/obesity. Childhood obesity is a strong predictor of future adiposity and is linked to changes in systolic blood pressure at a very young age. PMID- 26377102 TI - [Eyelid swelling with reduced general state of health]. PMID- 26377103 TI - [Characteristic neurological features, differential diagnostic criteria and medicinal treatment of idiopathic intracranial hypertension]. AB - Persistent headache and loss of visual acuity combined with papilledema are the predominant symptoms of idiopathic intracranial hypertension (IIH). The clinical signs are not different from those seen in other diseases with elevated intracranial pressure. To differentiate primary and secondary forms of increased intracranial pressure neuroimaging procedures and analysis of cerebrospinal fluid (CSF) are absolutely essential according to national and international guidelines. Lumbar puncture reveals an elevated opening pressure in cases of IIH as the only pathological finding. Treatment options are serial lumbar punctures combined with body weight reduction as well as medication with carbonic anhydrase inhibitors, such as acetazolamide and topiramate or diuretic therapy with furosemide. In some patients surgical options, e.g. optic nerve sheath fenestration, CSF shunting procedures including ventriculoperitoneal and lumboperitoneal shunt systems and bariatric surgery also have to be considered. In recent years modern neuroradiological procedures have also been applied (e.g. venous stenting in cases of sinus obstruction) in some centers. PMID- 26377104 TI - Evaluation of CYP3A4 inhibition and hepatotoxicity using DMSO-treated human hepatoma HuH-7 cells. AB - A human hepatoma cell line (HuH-7) was evaluated as a metabolically competent cell model to investigate cytochrome P450 3A4 (CYP3A4) inhibition, induction, and hepatotoxicity. First, CYP3A4 gene expression and activity were determined in HuH 7 cells under three culture conditions: 1-week culture, 3-week culture, or 1 % dimethyl sulfoxide (DMSO) treatment. HuH-7 cells treated with DMSO for 2 weeks after confluence expressed the highest CYP3A4 gene expression and activity compared to the other two culture conditions. Furthermore, CYP3A4 activity in DMSO-treated HuH-7 cells was compared to that in a human hepatoma cell line (HepG2/C3A) and human bipotent progenitor cell line (HepaRG), which yielded the following ranking: HepaRG > DMSO-treated HuH-7 >> HepG2/C3A cells. The effects of three known CYP3A4 inhibitors were evaluated using DMSO-treated HuH-7 cells. CYP3A4 enzyme inhibition in HuH-7 cells was further compared to human recombinant CYP3A4, indicating similar potency for reversible inhibitors (IC 50 within 2.5 fold), but different potency for the irreversible inhibitor. Next, induction of CYP3A4 activity was compared between DMSO-treated HuH-7 and HepaRG cells using two known inducers. DMSO-treated HuH-7 cells yielded minimal CYP3A4 induction compared to that in the HepaRG cells after 48-h treatments. Finally, the cytotoxicity of five known hepatotoxicants was evaluated in DMSO-treated HuH-7, HepG2/C3A, and HepaRG cells, and significant differences in cytotoxic sensitivity were observed. Overall, DMSO-treated HuH-7 cells are a valuable model for medium- or high-throughput screening of chemicals for CYP3A4 inhibition and hepatotoxicity. PMID- 26377105 TI - Cnga2 Knockout Mice Display Alzheimer's-Like Behavior Abnormities and Pathological Changes. AB - Olfactory dysfunction is recognized as a potential risk factor for Alzheimer's disease (AD). We have reported previously that olfactory deprivation by olfactory bulbectomy (OBX) induced Alzheimer's-like pathological changes and behavioral abnormalities. However, the acute OBX model undergoes surgical-induced brain parenchyma loss and unexpected massive hemorrhage so that it cannot fully mimic the progressive olfactory loss and neurodegeneration in AD. Here, we employed the mice loss of cyclic nucleotide-gated channel alpha 2 (Cnga2) which is critical for olfactory sensory transduction, to investigate the role of olfactory dysfunction in AD pathological process. We found that impaired learning and memory abilities, loss of dendrite spines, as well as decrement of synaptic proteins were displayed in Cnga2 knockout mice. Moreover, Abeta overproduction, tau hyperphosphorylation, and somatodendritic translocation were also found in Cnga2 knockout mice. Our findings suggest that progressive olfactory loss leads to Alzheimer's-like behavior abnormities and pathological changes. PMID- 26377106 TI - Tissue Plasminogen Activator Expression Is Restricted to Subsets of Excitatory Pyramidal Glutamatergic Neurons. AB - Although the extracellular serine protease tissue plasminogen activator (tPA) is involved in pathophysiological processes such as learning and memory, anxiety, epilepsy, stroke, and Alzheimer's disease, information about its regional, cellular, and subcellular distribution in vivo is lacking. In the present study, we observed, in healthy mice and rats, the presence of tPA in endothelial cells, oligodendrocytes, mastocytes, and ependymocytes, but not in pericytes, microglial cells, and astrocytes. Moreover, blockage of the axo-dendritic transport unmasked tPA expression in neurons of cortical and hippocampal areas. Interestingly, combined electrophysiological recordings, single-cell reverse transcription polymerase chain reaction (RT-PCR), and immunohistological analyses revealed that the presence of tPA is restricted to subsets of excitatory pyramidal glutamatergic neurons. We further evidenced that tPA is stored in synaptobrevin-2 positive glutamatergic synaptic vesicles. Based on all these data, we propose the existence of tPA-ergic neurons in the mature brain. PMID- 26377107 TI - Association of Microtubule Dynamics with Chronic Epilepsy. AB - Approximately 30 % of epilepsy cases are refractory to current pharmacological treatments through unknown mechanisms. Much work has been done on the role of synaptic components in the pathogenesis of epilepsy, but relatively little attention has been given to the potential role of the microtubules. We investigated the level of microtubule dynamic in 30 human epileptic tissues and two different chronic epilepsy rat models. The administration of microtubule modulating agent attenuated the progression of chronic epilepsy. By contrast, microtubule-depolymerizing agent aggravated the progression of chronic epilepsy. The electrophysiological index by whole-cell clamp was used to investigate the neuronal excitation and inhibitory synaptic transmission in brain slices after administration of microtubule-modulating agent and microtubule-depolymerizing agent. Interestingly, we found that microtubule-modulating agent significantly increased the frequency of action potential firing in interneurons, and significantly promoted the amplitudes and frequencies of miniature inhibitory postsynaptic currents. Microtubule-depolymerizing agent had an opposite effect. These findings suggest that modulating hyperdynamic microtubules may take an anti epileptic effect via postsynaptic mechanisms in interneurons. It could represent a potential pharmacologic target in epilepsy treatment. PMID- 26377109 TI - No correction, no retraction, no apology, no comment: paroxetine trial reanalysis raises questions about institutional responsibility. PMID- 26377108 TI - Systematic Genetic Analysis of the SMPD1 Gene in Chinese Patients with Parkinson's Disease. AB - To examine the association between the sphingomyelin phosphodiesterase 1, acid lysosomal (SMPD1) gene, and Parkinson's disease (PD) in Han Chinese from Central South part of Mainland China, we performed systematic genetic analysis in 502 Chinese Han patients with PD and 637 gender-, age-, and ethnicity-matched normal controls from Central South part of the Mainland China. We identified 11 single nucleotide variants and Leu-Ala (Val) repeat variants in the SMPD1 gene in our large cohort. Two novel missense variants, c.638A > C (p.H213P) and c.1673T > C (p.L558P), and a rare known missense variant, c.1805G > A (p.R602H, rs370129081), were identified in three sporadic PD cases. None of these three variants were observed in controls. Additionally, case-control analysis showed association between Leu-Ala (Val) repeat variants in SMPD1 and Chinese Han patients with PD (P = 0.015, chi (2) = 8.451). Our data provide supportive evidence that some genetic variants in SMPD1 increase the risk of PD in the Chinese Han population. PMID- 26377110 TI - In Reply to "'I Started to Feel Like a "Real Doctor"': Medical Students' Reflections on Their Psychiatry Clerkship". PMID- 26377111 TI - Large-scale ecological networks do work in an ecologically complex biodiversity hotspot. AB - Landscape-scale ecological networks (ENs) are interconnected conservation corridors of high-quality habitat used to mitigate the adverse effects of landscape fragmentation and to connect with protected areas. The effectiveness of ENs for biodiversity conservation and ecosystem function has been challenged. Here we show how an extensive system of ENs of remnant historic land was put in place at a large spatial scale (>0.5 million ha) in a plantation forestry context in a global biodiversity hotspot in southern Africa. These ENs can maintain indigenous and historic compositional and functional biodiversity, even in an area prone to the challenging effects of El Nino. Furthermore, ENs increase the effective size of local protected areas. Socio-ecological solutions and financial viability are also integrated as part of practical implementation of ENs. By adopting a retrospective analytical approach, biodiversity is maintained while also having productive forestry, making this a powerful agro-ecological approach on a large conservation-significant scale. PMID- 26377113 TI - Attentional Mechanisms in Autism, ADHD, and Autism-ADHD Using a Local-Global Paradigm. AB - OBJECTIVE: Cognitive flexibility or attentional set-shifting capacity has long been considered a core area of executive dysfunction for individuals with autism. Whether these difficulties are due to higher-level attentional difficulties associated with comorbid ADHD remains unclear. METHOD: The current study compared the performance of 48 participants with autism, ADHD, autism-ADHD, and a comparison group ( N = 12 per group) on a set-shifting task, which included a local-global paradigm. RESULTS: Results of this study revealed that participants with attentional difficulties (autism + ADHD and ADHD alone) exhibited a significant shifting cost (difference between maintaining and shifting attention). CONCLUSION: Attentional difficulties associated with ADHD may be associated with an enhanced attentional shifting cost. Implications of these results were discussed in relation to screening for ADHD symptoms in studies of individuals with autism which seek to determine the neuropsychological profile of this condition. PMID- 26377112 TI - Association of incident restless legs syndrome with outcomes in a large cohort of US veterans. AB - Restless legs syndrome is a common sleep disorder, but there is a paucity of large cohort studies examining the association of restless legs syndrome with clinical outcomes, including all-cause mortality, incident coronary heart disease, stroke and chronic kidney disease. From a nationally representative prospective cohort of over 3 million US veterans [93% male, median follow-up time of 8.1 years (interquartile range: 7.0-8.5 years)] with baseline estimated glomerular filtration rate >= 60 mL min(-1) 1.73 m(-2), a propensity-matched cohort of 7392 patients was created, and the association between incident restless legs syndrome and the following was examined: (1) all-cause mortality; (2) incident coronary heart disease; (3) incident strokes; and (4) incident chronic kidney disease defined as estimated glomerular filtration rate <60 mL min(-1) 1.73 m(-2). Associations were examined using Cox models. The mean +/- SD age of the propensity-matched cohort at baseline was 59 +/- 12 years; 89 and 8% of patients were white and black, respectively; 31% of the patients were diabetic; and the mean baseline estimated glomerular filtration rate was 83.9 +/- 15.1 mL min(-1) 1.73 m(-2). Propensity matching resulted in a balanced cohort, with the disappearance in baseline differences in comorbidities. Compared with restless legs syndrome-negative patients, incident restless legs syndrome was associated with 88% higher mortality risk [hazard ratio and 95% confidence interval: 1.88 (1.70-2.08)], and almost four times higher risk of coronary heart disease and stroke [hazard ratio: 3.97 (3.26-4.84) and 3.89 (3.07-4.94), respectively]. The risk of incident chronic kidney disease was also significantly higher in incident restless legs syndrome patients [hazard ratio: 3.17 (2.74 3.66)] compared with restless legs syndrome-negative counterparts. In this large and contemporary cohort of US veterans, incident restless legs syndrome was associated with higher risk of mortality, incident coronary heart disease, stroke and chronic kidney disease. PMID- 26377114 TI - Evolutionary history exposes radical diversification among classes of interaction partners of the MLLE domain of plant poly(A)-binding proteins. AB - BACKGROUND: Poly(A)-binding proteins (PABPs) are evolutionarily conserved proteins that have important functions in the regulation of translation and the control of mRNA stability in eukaryotes. Most PABPs encode a C-terminal domain known as the MLLE domain (previously PABC or CTC), which can mediate protein interactions. In earlier work we identified and predicted that four classes of MLLE-interacting proteins were present in Arabidopsis thaliana, which we named CID A, B, C, and D. These proteins encode transcription-activating domains (CID A), the Lsm and LsmAD domains of ataxin-2 (CID B), the CUE and small MutS-related domains (CID C), and two RNA recognition domains (CID D). We recently found that a novel class that lacks the LsmAD domain is present in CID B proteins. RESULTS: We extended our analysis to other classes of CIDs present in the viridiplantae. We found that novel variants also evolved in classes CID A and CID C. A specific transcription factor domain is present in a distinct lineage in class A, and a variant that lacks at least two distinct domains was also identified in a divergent lineage in class C. We did not detect any variants in Class D CIDs. This class often consists of four to six highly conserved RNA-binding proteins, which suggests that major redundancy is present in this class. CONCLUSIONS: CIDs are likely to operate as components of posttranscriptional regulatory assemblies. The evident diversification of CIDs may be neutral or may be important for plant adaptation to the environment and for acquisition of specific traits during evolution. The fact that CIDs subclasses are maintained in early lineages suggest that a presumed interference between duplicates was resolved, and a defined function for each subclass was achieved. PMID- 26377117 TI - Corrigendum to 'Searching for new mechanisms of myocardial fibrosis with diagnostic and/or therapeutic potential'[Eur J Heart Fail 2015; 17:764-771]. PMID- 26377116 TI - Corrigendum to 'Clinical picture and risk prediction of short-term mortality in cardiogenic shock' [Eur J Heart Fail] 2015 May;17(5):501-9. doi: 10.1002/ejhf.260. AB - The name of J Martin-Sanchez should read FJ Martin-Sanchez (in the list of investigators). PMID- 26377118 TI - Random lasing in Eu3+ doped borate glass-ceramic embedded with Ag nanoparticles under direct three-photon excitation. AB - We report the observation of random lasing from Eu(3+) doped borate glass ceramic films embedded with Ag nanoparticles through three-photon absorption at room temperature. Under 1179 nm ultrashort femtosecond pulse excitation, discrete sharp peaks with linewidth ~0.4 nm emerge randomly from a broad emission band with peak wavelength at ~612 nm. In addition, the number of sharp peaks increases with the increase of excitation power. We also show that the emission spectrum varies with different observation angles and the corresponding lasing threshold is dependent on the excitation area. Hence, we verify unambiguously that the Eu(3+) doped borate glass ceramic film supports random lasing action via three photon absorption excitation. In addition, Ag nanoparticles, which act as light scatterers, allow the formation of random microcavities inside the bulk film. PMID- 26377119 TI - Dementia and intentional and unintentional poisoning in older people: a 10 year review of hospitalization records in New South Wales, Australia - CORRIGENDUM. AB - The authors would like to apologise for a typographical error in the abstract of the above mentioned article. In the results section of the abstract on the first page of the article, the first odds ratio that refers to 'aged care facilities' should be (OR 5.44; 95% CI 4.43-6.67) and the second odds ratio that refers to health service facilities should be (OR 4.56; 95%CI 4.06-5.13). PMID- 26377120 TI - Speech pathologists' perspectives on transitioning to telepractice: What factors promote acceptance? AB - Little is understood about factors that influence speech-language pathologists' (SLPs') acceptance of telepractice. The aim of this study was to investigate SLPs' perceptions and experiences of transitioning to a school-based telepractice service to identify factors that contributed to positive clinician attitudes. In depth interviews were conducted with 15 SLPs who recently commenced providing school-based telepractice services. Interviews were recorded and transcribed verbatim and thematic analysis was used to interpret interviews, with themes compared and contrasted across the group. Results indicated that although SLPs reported initially having mixed feelings towards telepractice, they later evaluated telepractice positively and viewed it as a legitimate service delivery mode. The overarching theme was that positive beliefs about telepractice were associated with perceptions of its consistency with the underlying principles of face-to-face therapy. In evaluating telepractice, SLPs considered: (a) therapeutic relationships with children; (b) collaboration with parents and teachers; (c) adequacy of technology and resources; and (d) access to support for learning telepractice. Therapy assistants and specific clinician attributes emerged as key strategies used to manage threats to acceptability. Preparation of SLPs transitioning to telepractice should address factors that support positive experiences with, and attitudes towards, telepractice to ensure that training achieves the greatest, most sustained change. PMID- 26377121 TI - Monitoring ear health through a telemedicine-supported health screening service in Queensland. AB - The prevalence of ear disease and hearing loss is greater for Indigenous children than for their non-Indigenous counterparts. In 2009, we established a mobile ear screening service in South Burnett, in which an Indigenous Health Worker (IHW) assesses children at school and shares results by telemedicine with ear, nose and throat (ENT) specialists, who in turn provide review and biannual surgical outreach to the community. We reviewed service data for the first six years of the service (Jan 2009-Dec 2014), to calculate: total number of completed assessments; total number of patients failing at least one screening test; and overall proportion of failed screening assessments per annum. Subgroup analysis was conducted by usual home postcode. The service has provided 5539 screening assessments. The mean screening failure rate for children outside of postcode 4605 (Cherbourg/Murgon area) was 22% (range 17-29%) and 38% for children living inside postcode 4605 (range 34-41%). While screening activity has increased by more than 50% since 2009, there has been a slight reduction in the proportion of children failing assessment, with the mean failure rate changing from 33% in 2009 to 26% in 2014. These early results suggest that community-based screening, integrated with specialist ENT services may improve ear and hearing health. PMID- 26377122 TI - Accuracy of dental images for the diagnosis of dental caries and enamel defects in children and adolescents: A systematic review. AB - AIM: The aim of this review was to determine if photographic examination and subsequent image analysis provides comparable accuracy to visual inspection for the diagnosis of common dental conditions in children and adolescents. METHODS: We searched the PubMed database for studies that compared diagnostic accuracy of the two inspection techniques. Studies were screened for inclusion and were assessed for quality and risk of bias using the quality assessment of diagnostic accuracy studies tools. Findings were reported according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA). FINDINGS: Sixteen studies met the inclusion criteria. Nine of the included studies evaluated dental caries and eight evaluated enamel defects (one study evaluated both conditions). CONCLUSIONS: Three studies found image analysis to be superior. For the remaining six studies the diagnostic accuracy was comparable. For enamel defects, three studies found image analysis to be superior, two found visual inspection to be superior and three studies reported comparable diagnostic accuracy. Most studies have found at least comparable results between photographic and visual inspection techniques. However, the wide variation in equipment and personnel used for the collection and interpretation of photographic images made it impossible to generalise the results. It remains unclear exactly how effective store-and-forward teledentistry is for the diagnosis of common dental conditions in children. PMID- 26377123 TI - Teledermatology as a means to improve access to inpatient dermatology care. AB - Many hospitals have limited inpatient dermatology consultation access. Most dermatologists are outpatient-based and may find the distance and time to complete inpatient consultations prohibitive. Teledermatology may improve access to inpatient dermatology care by reducing barriers of distance and time. We conducted a prospective two-phase pilot study at two academic hospitals comparing time needed to complete inpatient consultations after resident dermatologists initially evaluated patients, called average handling time (AHT), and time needed to respond to the primary team, called time to response (TTR), with and without teledermatology with surveys to capture changes in dermatologist opinion on teledermatology. Teledermatology was only used in the study phase, and patients were seen in-person in both study phases. Teledermatology alone sufficiently answered consultations in 10 of 25 study consultations. The mean AHT in the study phase (sAHT) was 26.9 min compared to the baseline phase (bAHT) of 43.5 min, a 16.6 min reduction (p = 0.004). The 10 study cases where teledermatology alone was sufficient had mean study TTR (sTTR) of 273.3 min compared to a baseline TTR (bTTR) of 405.7 min, a 132.4 min reduction (p = 0.032). Teledermatology reduces the time required for an attending dermatologist to respond and the time required for a primary team to receive a response for an inpatient dermatology consultation in a subset of cases. These findings suggest teledermatology can be used as a tool to improve access to inpatient dermatology care. PMID- 26377124 TI - Using mobile technology to motivate adolescents with type 1 diabetes mellitus: A systematic review of recent literature. AB - INTRODUCTION: Behavioural interventions have been shown to improve outcomes in patients with type 1 diabetes mellitus (T1DM). There are a small number of studies that suggest text-messages (TM), native mobile applications (NMAs), and other mobile tools may be useful platforms for delivering behavioural interventions to adolescents. AIM: The aim of this study was to explore, by way of a systematic review of available literature, (a) the outcomes of interventions using mobile technology for youth with T1DM and (b) what mobile technologies, functional design elements and aesthetic design elements have the best evidence to support their use. METHODS: A search of six online databases returned 196 unique results, of which 13 met the inclusion criteria. RESULTS: Four studies were randomised controlled trials (RCTs), and all others prospective cohort studies. TM (10) was the most common intervention technology, while NMAs were used in four studies. The most common outcome measured was HbA1c (9); however, only three studies showed a significant decrease. Similarly, the results reported for other outcome measures were mixed. The studies included in this review suggest that interventions which have data collection and clinician support functionality may be more effective in improving adherence and glycaemic control, but more evidence is needed. Further, the evidence base supporting the use of NMAs in T1DM management for adolescents is weak, with most studies adopting TM as the intervention tool. Overall, the studies lack adequate descriptions of their methodology, and better quality studies are required to inform future intervention design. PMID- 26377125 TI - Tele-health services for the elderly: A novel southern Italy family needs oriented model. AB - INTRODUCTION: The world population is aging. By 2050, the global population aged over 65 years will have doubled, leading to big societal challenges for ensuring healthy, independent, and productive lives for older people. Thus, innovative local and national initiatives for e-health services are growing in an attempt to overcome such problems. METHODS: We examined the effects of a telehealth system, i.e. tele-monitoring of vital parameters and neurological/psychological tele counseling, within a family-centred service provided by a local day centre. We evaluated the clinical and neurobehavioral symptoms of 18 elderly patients (aged 65 years and over) and the care burden of their 20 caregivers, besides the usability of the tool. RESULTS: The one-way repeated analysis revealed a significant worsening in daily living activities (p < 0.01 and p = 0.02, respectively for Activities of Daily Living (ADL) and Independent IADL (IADL)) versus a significant improvement of the patients' psychiatric condition (p < 0.001), besides a significant gradual reduction of the caregivers burden (p < 0.001). Health status perception increased through time (from an average score of 5.67 +/- 1.08 at baseline to 7.72 +/- 1.32 at the end of the study). DISCUSSION: It appears that a telehealth system integrated in a local health care service may significantly improve elderly persons' behaviour, and also reduce the caregivers' burden. PMID- 26377126 TI - A proof-of-concept evaluation of a cloud-based store-and-forward telemedicine app for screening for oral diseases. AB - OBJECTIVE: It is widely considered that telemedicine can make positive contributions to dental practice. This study aimed to evaluate a cloud-based telemedicine application for screening for oral diseases. METHODS: A telemedicine system, based on a store-and-forward method, was developed to work as a platform for data storage. An Android application was developed to facilitate entering demographic details and capturing oral photos. As a proof-of-concept, six volunteers were enrolled in a trial to obtain oral images using smartphone cameras. Following an onsite oral examination, images of participants' teeth were obtained by a trained dental assistant. Oral images were directly uploaded from the smartphone to a cloud-based server via broadband network. The assessments of oral images by offsite dentists were compared with those carried out via face-to face oral examinations. RESULTS: A complete set of 30 oral images was obtained from all six participants. Out of 192 teeth reviewed, the proportion of ungradable teeth was 8%. Sensitivity and specificity of teledental screening were 57% and 100% respectively. The inter-grader agreement estimated for two examination modalities and between two teledental graders was 70% and 62% respectively. Findings indicate that the proposed system for screening of oral diseases can be implemented to provide a valid and reliable alternative to traditional oral screening. CONCLUSION: This study provided evidence that a robust system for store-and-forward screening for dental problems can be developed, and leads to the need for further testing of its robustness to confirm the accuracy and reliability of the teledentistry system. PMID- 26377127 TI - Influence of the Ring Size on the Binding Ability of FTO Investigated by Fluorescence Spectroscopy. AB - The fat mass and obesity associated protein (FTO) is a potential target for anti obesity medicines. In this paper, we have synthesized two potential inhibitors for FTO, three-member-ring compound (W 3 ) and four-member-ring compound (W 4 ). The interactions of fat mass and obesity-associated (FTO) protein with W 3 (or W 4 ) have been studied by spectral method. Results show the intrinsic fluorescence is quenched by the W 3 (or W 4 ). The thermodynamics parameters indicate hydrophobic interaction play a major role in the interactions. The results of synchronous fluorescence spectra demonstrate that the microenvironments of Trp residue of FTO are disturbed by W 3 and W 4 . Results showed that W 3 are stronger quenchers and bind to FTO with the higher affinity than W 4 . The influence of molecular structure on the binding aspects has been investigated. PMID- 26377128 TI - Preparation and Effect of Lighting on Structures and Properties of GSH Capped ZnSe QDs. AB - L-glutathione (GSH) capped ZnSe quantum dots (QDs) were prepared by microwave assisted aqueous synthesis. Then, the resulting QDs were illuminated under dark, ultraviolet light and incandescent light, respectively. Thereby effect of lighting on the structures and properties of QDs were studied systematically. It was revealed that particle size and element content of QDs took a sharp change after irradiation, while the crystal structure maintains nearly unaffected. Comparing to the ZnSe QDs under dark condition, counterparts irradiated by UV light possessed outstanding sphericity, size distribution and dispersion. And the content of sulfur (S) in ZnSe QDs irradiated by UV light was much higher relatively. The effect of lighting on vibration peaks of O-H was considerable. However, this effect was observed to be weak on other chemical bonds. The possible explanation ascribes to photo-chemical interactions can occur between S H and O-H bonds on the surface of GSH ligand. The lighting induced GSH to occur photocatalytic oxidation on the surface of ZnSe QDs, which improved the optical properties of QDs. The effects of lighting rely on irradiation types, the sequence is UV light, incandescent light and dark from high to low. PMID- 26377129 TI - Molecular characterization of a eukaryotic-like phenol hydroxylase from Corynebacterium glutamicum. AB - This study focuses on the genetic and biochemical characterization of phenol hydroxylase (Phe, NCgl2588) from Corynebacterium glutamicum that shares 31% identity in amino acids with phenol hydroxylase from yeast Trichosporon cutaneum but less similarity with that from bacteria. The phe deletion mutant significantly reduced its ability to grow with phenol as the sole carbon and energy source. Expression of the phe gene was strongly induced with phenol and also subject to the control of carbon catabolite repression (CCR). The molecular weight of purified Phe protein determined by gel filtration chromatography was 70 kDa, indicating that Phe exists as a monomer in the purification condition. However, Phe protein pre-incubated with phenol showed a molecular weight of 140 kDa, suggesting that Phe is likely active as a dimer. In addition to phenol, the Phe protein could utilize various other phenolic compounds as substrates. Site directed mutagenesis revealed that D75, P261, R262, R269, C349 and C476 are key amino acid residues closely related to the enzyme activity of Phe. PMID- 26377130 TI - Characteristics of inositol phosphorylceramide synthase and effects of aureobasidin A on growth and pathogenicity of Botrytis cinerea. AB - Inositol phosphorylceramide (IPC) synthase is the key enzyme with highly conserved sequences, which is involved in fungal sphingolipid biosynthesis. The antibiotic aureobasidin A (AbA) induces the death of fungi through inhibiting IPC synthase activity. The mutations of AUR1 gene coding IPC synthase in fungi and protozoa causes a resistance to AbA. However, the mechanism of AbA resistance is still elusive. In this paper, we generated two mutants of Botrytis cinerea with AbA-resistance, BcAUR1a and BcAUR1b, through UV irradiation. BcAUR1a lost an intron and BcAUR1b had three amino acid mutations (L197P, F288S and T323A) in the AUR1 gene. AbA strongly inhibits the activity of IPC synthase in wild-type B. cinerea, which leads to distinct changes in cell morphology, including the delay in conidial germination, excessive branching near the tip of the germ tube and mycelium, and the inhibition of the mycelium growth. Further, AbA prevents the infection of wild-type B. cinerea in tomato fruits via reducing oxalic acid secretion and the activity of cellulase and pectinase. On the contrary, AbA has no effect on the growth and pathogenicity of the two mutants. Although both mutants show a similar AbA resistance, the molecular mechanisms might be different between the two mutants. PMID- 26377131 TI - Purification, sequencing and evaluation of a divergent phytase from Penicillium oxalicum KCTC6440. AB - A fungal strain producing high levels of phytase was purified to homogeneity from Penicillium oxalicum KCTC6440 (PhyA). The molecular mass of the purified PhyA was 65 kDa and optimal activity occurred at 55 degrees C. The enzyme was stable in a pH range of 4.5-6.5, with an optimum performance at pH 5.5. The Km value for the substrate sodium phytate was 0.48 mM with a Vmax of 672 U/mg. The enzyme was inhibited by Ca(2+), Cu(2+), and Zn(2+), and slightly enhanced by EDTA. The PhyA efficiently released phosphate from feedstuffs such as soybean, rich bran and corn meal. The PhyA gene was cloned in two steps of degenerate PCR and inverse PCR and found to comprise 1501 bp and encode 461 amino acid residues. The enzyme was found to have only 13 amino acids differing to the known PhyA from other Penicillium sp., but has distinct enzyme characteristics. Computational analysis showed that PhyA possessed more positively charged residues in the active sites compared to other PhyA molecules, which may explain the broader pH spectrum. PMID- 26377132 TI - Construction of novel shuttle expression vectors for gene expression in Bacillus subtilis and Bacillus pumilus. AB - A native plasmid (pSU01) was detected by genome sequencing of Bacillus subtilis strain S1-4. Two pSU01-based shuttle expression vectors pSU02-AP and pSU03-AP were constructed enabling stable replication in B. subtilis WB600. These vectors contained the reporter gene aprE, encoding an alkaline protease from Bacillus pumilus BA06. The expression vector pSU03-AP only possessed the minimal replication elements (rep, SSO, DSO) and exhibited more stability on structure, suggesting that the rest of the genes in pSU01 (ORF1, ORF2, mob, hsp) were unessential for the structural stability of plasmid in B. subtilis. In addition, recombinant production of the alkaline protease was achieved more efficiently with pSU03-AP whose copy number was estimated to be more than 100 per chromosome. Furthermore, pSU03-AP could also be used to transform and replicate in B. pumilus BA06 under selective pressure. In conclusion, pSU03-AP is expected to be a useful tool for gene expression in Bacillus subtilis and B. pumilus. PMID- 26377134 TI - Exploring the in vitro thrombolytic potential of streptokinase-producing beta hemolytic Streptococci isolated from bovine milk. AB - The aim of this study was to isolate and characterize streptokinase-producing beta-hemolytic Streptococcus sp. from bovine milk. A total of 50 milk samples were collected randomly from different breeds of cow and goat (Vellore, Tamil Nadu, India). The samples were characterized and screened for streptokinase producing isolates using microbial and biochemical analysis. About 97 colonies were isolated from milk samples showing hemolytic patterns of alpha (19.6%), beta (24.7%) and gamma (55.6 %). Out of 20beta-hemolytic isolates, only 6 colonies (VB2, VB3, VB8, VB14, VB16, and VB17) were identified as beta-hemolytic Streptococci as potent producers of streptokinase. VB2 and VB14 showed the greatest streptokinase activities of 265 U mL(-1) and 225 U mL(-1), respectively. Based on biochemical and molecular characterization, the potent isolates VB2 and VB14 were identified and confirmed as S. equinus and S. agalactiae, respectively. The identified strains were named Streptococcus equinus VIT_VB2 (GenBank accession no. JX406835) and Streptococcus agalactiae VITVS5 (GenBank accession No. KF186620) The strains isolated from bovine milk provide a variance in the fibrinolytic activity on blood clots. The current study has demonstrated that the isolation of streptokinase producers from bovine milk, and the production of streptokinase from novel strain, enhanced the fibrinolytic activity. This study is the first to report that Streptococcus equinus produces streptokinase. PMID- 26377133 TI - Effect of a microbiota activator on accumulated ammonium and microbial community structure in a pilot-scale membrane bioreactor. AB - Microbiota activators (MAs) have been used to improve the reactor performances of biological wastewater treatment processes. In this study, to remove ammonium (NH4(+)) accumulated during the pre-operation of a pilot-scale membrane bioreactor (MBR) under high-organic-loading conditions, an MA was added to the MBR system and the resulting changes in reactor performances and microbial communities were monitored for 12 days. The NH4(+) concentrations in the sludge and effluent decreased (from 427 to 246 mg/L in the sludge (days 1-9)), and mixed liquor suspended solid increased (from 6,793 to 11,283 mg/L (days 1-12)) after the addition of MA. High-throughput Illumina sequencing of 16S rRNA genes revealed that the microbial community structure changed along with the NH4(+) removal resulting from the MA addition. In particular, the relative abundance of an Acidovorax-related operational taxonomic unit (OTU) increased significantly, accounting for approximately 50% of the total microbial population at day 11. In contrast, the ammonia-oxidizing bacteria and archaea showed low abundances (<0.05%), and no anaerobic ammonia oxidizers were detected. These results suggested that the Acidovorax-related OTU was mainly involved in the NH4(+) removal in the MBR, probably due to its ammonia-assimilating metabolism. PMID- 26377135 TI - Nar is the dominant dissimilatory nitrate reductase under high pressure conditions in the deep-sea denitrifier Pseudomonas sp. MT-1. AB - In this paper, relative nitrate reductase activities of the soluble and membrane fractions of MT-1 grown anaerobically under atmospheric pressure in the presence of 30 mM NaNO3 were measured. In the analyses, the diazocoupling method was employed to determine the concentration of nitrite formed. Follow-up recent experiments have revealed that formed coupling compound lose its color rapidly, but this instability is unusual. The authors recognized the possibility that they failed to quantify the accurate concentration of nitrite formed and agree the additional in-depth analyses should be performed. Thus, the JGAM editorial board agreed to retract the paper. PMID- 26377137 TI - Clinicopathologic features, management and outcomes of blastoid variant of mantle cell lymphoma: a Nebraska Lymphoma Study Group Experience. AB - The objective of this retrospective study (N = 169) was to compare the overall survival (OS) of different subtypes of mantle cell lymphoma (MCL) treated by the Nebraska Lymphoma Study Group between 1984 and 2012. The overall response rate to various therapies including stem cell transplant (SCT) was similar (p = 0.44) between blastoid, diffuse and nodular subtypes. At 5 years, blastoid and diffuse subtypes had worse OS (overall p = 0.005) compared to nodular subtype. In multivariate analysis, the blastoid and diffuse subtypes had similar risk of death (p = 0.14) whereas the nodular subtype had a lower risk compared to blastoid (HR 0.48, 95% CI 0.27-0.87, p = 0.01). The use of SCT was associated with lower risk of death. In univariate analysis, blastoid subtype had better OS with intensive upfront therapy. In conclusion, the OS of blastoid subtype is worse than nodular MCL but may improve with the use of SCT and probably intensive induction therapy. PMID- 26377136 TI - Placental phenotype and resource allocation to fetal growth are modified by the timing and degree of hypoxia during mouse pregnancy. AB - The placenta adapts its transport capacity to nutritional cues developmentally, although relatively little is known about placental transport phenotype in response to hypoxia, a major cause of fetal growth restriction. The present study determined the effects of both moderate hypoxia (13% inspired O2) between days (D)11 and D16 or D14 and D19 of pregnancy and severe hypoxia (10% inspired O2) from D14 to D19 on placental morphology, transport capacity and fetal growth on D16 and D19 (term~D20.5), relative to normoxic mice in 21% O2. Placental morphology adapted beneficially to 13% O2; fetal capillary volume increased at both ages, exchange area increased at D16 and exchange barrier thickness reduced at D19. Exposure to 13% O2 had no effect on placental nutrient transport on D16 but increased placental uptake and clearance of (3)H-methyl-D-glucose at D19. By contrast, 10% O2 impaired fetal vascularity, increased barrier thickness and reduced placental (14)C-methylaminoisobutyric acid clearance at D19. Consequently, fetal growth was only marginally affected in 13% O2 (unchanged at D16 and -5% at D19) but was severely restricted in 10% O2 (-21% at D19). The hypoxia-induced changes in placental phenotype were accompanied by altered placental insulin-like growth factor (IGF)-2 expression and insulin/IGF signalling, as well as by maternal hypophagia depending on the timing and severity of the hypoxia. Overall, the present study shows that the mouse placenta can integrate signals of oxygen and nutrient availability, possibly through the insulin-IGF pathway, to adapt its phenotype and optimize maternal resource allocation to fetal growth during late pregnancy. It also suggests that there is a threshold between 13% and 10% inspired O2 at which these adaptations no longer occur. PMID- 26377138 TI - Natural variation, differentiation, and genetic trade-offs of ecophysiological traits in response to water limitation in Brachypodium distachyon and its descendent allotetraploid B. hybridum (Poaceae). AB - Differences in tolerance to water stress may underlie ecological divergence of closely related ploidy lineages. However, the mechanistic basis of physiological variation governing ecogeographical cytotype segregation is not well understood. Here, using Brachypodium distachyon and its derived allotetraploid B. hybridum as model, we test the hypothesis that, for heteroploid annuals, ecological divergence of polyploids in drier environments is based on trait differentiation enabling drought escape. We demonstrate that under water limitation allotetraploids maintain higher photosynthesis and stomatal conductance and show earlier flowering than diploids, concordant with a drought-escape strategy to cope with water stress. Increased heterozygosity and greater genetic variability and plasticity of polyploids could confer a superior adaptive capability. Consistent with these predictions, we document (1) greater standing within population genetic variation in water-use efficiency (WUE) and flowering time in allotetraploids, and (2) the existence of (nonlinear) environmental clines in physiology across allotetraploid populations. Increased gas exchange and diminished WUE occurred at the driest end of the gradient, consistent with a drought-escape strategy. Finally, we found that allotetraploids showed weaker genetic correlations than diploids congruous with the expectation of relaxed pleiotropic constraints in polyploids. Our results suggest evolutionary divergence of ecophysiological traits in each ploidy lineage. PMID- 26377140 TI - Understanding healthcare processes: how marginal gains can improve quality and value for children and families. AB - Understanding how to identify and improve clinical pathways has proven a key tool in quality improvement. These techniques originated beyond healthcare, but are increasingly applied to healthcare. This paper outlines the history of the technique transfer and how to use in clinical practice. PMID- 26377139 TI - Influence of deposition substrate temperature on the morphology and molecular orientation of chloroaluminum phthalocyanine films as well the performance of organic photovoltaic cells. AB - The dependence of the morphology of neat chloroaluminum phthalocyanine (ClAlPc) films on substrate temperature (Tsub) during deposition is investigated by variable angle spectroscopic ellipsometry (VASE), x-ray diffraction (XRD), and atomic force microscopy (AFM) to obtain detailed information about the molecular orientation, phase separation, and crystallinity. AFM images indicate that both grain size and root mean square (RMS) roughness noticeably increase with Tsub both in neat and blend films. Increasing Tsub from room temperature to 420 K increases the horizontal orientation of the ClAlPc molecules with an increase of the mean molecular tilt angle from 60.13 degrees (300 K) to 65.86 degrees (420 K). The UV-vis absorption band of the corresponding films increases and the peak wavelength slightly red shifts with the Tsub increase. XRD patterns show a clear diffraction peak at Tsub over 390 K, implying the pi-stacking of interconnected ClAlPc molecules at high Tsub. Planar and bulk heterojunction (BHJ) photovoltaic cells containing pristine ClAlPc films and ClAlPc:C60 blend films fabricated at Tsub of 390 K show increases in the power conversion efficiency (etaPCE) of 28% (etaPCE = 3.12%) and 36% (etaPCE = 3.58%), respectively, relative to devices as deposited at room temperature. The maximum short circuit current in BHJs is obtained at 390 K in the Tsub range from 300 K to 450 K. PMID- 26377142 TI - Atopic dermatitis. AB - Atopic dermatitis (also known as atopic eczema) is a chronic inflammatory skin disease that is characterised by intense itching and recurrent eczematous lesions. Although it most often starts in infancy and affects two of ten children, it is also highly prevalent in adults. It is the leading non-fatal health burden attributable to skin diseases, inflicts a substantial psychosocial burden on patients and their relatives, and increases the risk of food allergy, asthma, allergic rhinitis, other immune-mediated inflammatory diseases, and mental health disorders. Originally regarded as a childhood disorder mediated by an imbalance towards a T-helper-2 response and exaggerated IgE responses to allergens, it is now recognised as a lifelong disposition with variable clinical manifestations and expressivity, in which defects of the epidermal barrier are central. Present prevention and treatment focus on restoration of epidermal barrier function, which is best achieved through the use of emollients. Topical corticosteroids are still the first-line therapy for acute flares, but they are also used proactively along with topical calcineurin inhibitors to maintain remission. Non-specific immunosuppressive drugs are used in severe refractory cases, but targeted disease-modifying drugs are being developed. We need to improve understanding of the heterogeneity of the disease and its subtypes, the role of atopy and autoimmunity, the mechanisms behind disease-associated itch, and the comparative effectiveness and safety of therapies. PMID- 26377141 TI - Evaluation of Alpha-Thalassemia Mutations in Cases with Hypochromic Microcytic Anemia: The Istanbul Perspective. AB - OBJECTIVE: Alpha thalassemia syndromes are caused by mutations on one or more of the four alpha-globin genes. Mutations could be either more commonly deletional or non-deletional. As some deletions (3.7 and 4.2) cause alpha+-thalassemia, some cause (-20.5, MED, THAI, FIL) alpha0 -thalassemia. The aim of this study was to determine alpha thalassemia mutations in patients with unsolved hypochromic microcytic anemia and to evaluate types of mutations. MATERIAL AND METHODS: Two hundred six patients with hypochromic microcytic anemia were evaluated for alpha thalassemia. A venous blood sample of 2 mL was drawn from each patient for DNA isolation. The samples were investigated for alpha-thalassemia mutations by using the Vienna Lab alpha-Globlin StripAssay TM commercial kit. RESULTS: Fourteen different mutations were determined in 95 (46.1%) patients. The most common mutation was the 3.7 single gene deletion and was found in 37 patients (n=37/95, 39%). Others common mutations were the 20.5 kb double gene deletion (n=20 patients, 21%), MED double gene deletion (n=17 patients, 17.9%), alpha2 IVS1 (n=10 patients, 10.5%), alpha2 cd142 Hb Koya Dora (n=6 patients, 6.3%), alpha2 polyA1 (Saudi type) (n=6 patients, 6.3%), 4.2 single gene deletion (n=4 patients, 4.2%), alpha1 cd14 (n=2 patients, 2.1%), and -FIL mutation (n=2 patients 2.1%), respectively. Hb Adana, Hb Icaria, alpha2 init cd and alpha2 polyA2 (Turkish type) were found in 1% of the patients (n=1). Seven patients (7.4%) had alpha thalassemia triplication. In our study, three mutations (Hb Icaria, alpha1 cd14, alpha2 init.cd) were determined firstly in Turkey. Seven mutations (-SEA, -THAI, Hb Constant Spring, alpha2 cd19, alpha2 cd59, alpha2 cd125, Hb Pakse) were not determined in this study. CONCLUSION: Alpha thalassemia should be considered in the differential diagnosis of hypochromic microcytic anemia especially in cases without iron deficiency and b-thalassemia carrier state. Genetic testing should be performed for the suspicious cases. We also recommend that a national database with all mutations in Turkey should be created to screen the alpha thalassemia cost-effectively. PMID- 26377143 TI - Tuberculosis. AB - Although the worldwide incidence of tuberculosis has been slowly decreasing, the global disease burden remains substantial (~9 million cases and ~1.5 million deaths in 2013), and tuberculosis incidence and drug resistance are rising in some parts of the world such as Africa. The modest gains achieved thus far are threatened by high prevalence of HIV, persisting global poverty, and emergence of highly drug-resistant forms of tuberculosis. Tuberculosis is also a major problem in health-care workers in both low-burden and high-burden settings. Although the ideal preventive agent, an effective vaccine, is still some time away, several new diagnostic technologies have emerged, and two new tuberculosis drugs have been licensed after almost 50 years of no tuberculosis drugs being registered. Efforts towards an effective vaccine have been thwarted by poor understanding of what constitutes protective immunity. Although new interventions and investment in control programmes will enable control, eradication will only be possible through substantial reductions in poverty and overcrowding, political will and stability, and containing co-drivers of tuberculosis, such as HIV, smoking, and diabetes. PMID- 26377144 TI - Access to pure and highly volatile hydrochalcogenide ionic liquids. AB - The reaction of methylcarbonate ionic liquids with H2S or H2Se offers a highly selective synthesis of analytically pure, well-defined and soluble hydrosulphide and hydroselenide organic salts of general interest. Among them, imidazolium hydrochalcogenides show an astonishingly high volatility for cation-aprotic ILs, which allows their quantitative sublimation below 100 degrees C/10(-2) mbar and actually results in ionic single crystal growth from the gas phase. Vaporisation and decomposition characteristics were investigated by isothermal TGA measurements and DFT calculations. PMID- 26377145 TI - Enzymology of Pyran Ring A Formation in Salinomycin Biosynthesis. AB - Tetrahydropyran rings are a common feature of complex polyketide natural products, but much remains to be learned about the enzymology of their formation. The enzyme SalBIII from the salinomycin biosynthetic pathway resembles other polyether epoxide hydrolases/cyclases of the MonB family, but SalBIII plays no role in the conventional cascade of ring opening/closing. Mutation in the salBIII gene gave a metabolite in which ring A is not formed. Using this metabolite in vitro as a substrate analogue, SalBIII has been shown to form pyran ring A. We have determined the X-ray crystal structure of SalBIII, and structure-guided mutagenesis of putative active-site residues has identified Asp38 and Asp104 as an essential catalytic dyad. The demonstrated pyran synthase activity of SalBIII further extends the impressive catalytic versatility of alpha+beta barrel fold proteins. PMID- 26377146 TI - pH-dependence of single-protein adsorption and diffusion at a liquid chromatographic interface. AB - pH is a common mobile phase variable used to control protein separations due to the tunable nature of amino acid and adsorbent charge. Like other column variables such as column density and ligand loading density, pH is usually optimized empirically. Single-molecule spectroscopy extracts molecular-scale data to provide a framework for mechanistic optimization of pH. The adsorption and diffusion of a model globular protein, alpha-lactalbumin, was studied by single molecule microscopy at a silica-aqueous interface analogous to aqueous normal phase and hydrophilic interaction chromatography and capillary electrophoresis interfaces at varied pH. Electrostatic repulsion resulting in free diffusion was observed at pH above the isoelectric point of the protein. In contrast, at low pH strong adsorption and surface diffusion with either no (D ~ 0.01 MUm(2) /s) or translational (D ~ 0.3 MUm(2) /s) motion was observed where the protein likely interacted with the surface through electrostatic, hydrophobic, and hydrogen bonding forces. The fraction of proteins immobilized could be increased by lowering the pH. These results show that retention of proteins at the silica interface cannot be viewed solely as an adsorption/desorption process and that the type of surface diffusion, which ultimately leads to ensemble chromatographic separations, can be controlled by tuning long-range electrostatic and short-range hydrophobic and hydrogen bonding forces with pH. PMID- 26377147 TI - Why and how immunohistochemistry should now be used to screen for the BRAFV600E status in metastatic melanoma? The experience of a single institution (LCEP, Nice, France). AB - BACKGROUND: Knowledge of the BRAFV600E status is mandatory in metastatic melanoma patients (MMP). Molecular biology is currently the gold standard method for status assessment. OBJECTIVES: We assessed and compared the specificity, sensibility, cost-effectiveness and turnaround time (TAT) of immunohistochemistry (IHC) and molecular biology for detection of the BRAFV600E mutation in 188 MMP. METHODS: IHC, with the VE1 antibody, and pyrosequencing analysis were performed with formalin fixed paraffin embedded tumour samples. RESULTS: The BRAFV600E mutation was detected by pyrosequencing in 91/188 (48%) patients. IHC was strongly positive (3+) in all of these 91 cases. IHC was strongly positive in 9/188 (5%) cases in which the molecular testing failed due to non-amplifiable DNA. Weak or moderate staining was noted in 10/188 (5%) cases in which the molecular biology identified BRAF wild-type tumours. The ratio of the global cost for IHC/molecular biology testing was 1 : 2.2. The average TAT was 48 h vs. 96 h, for IHC vs. molecular biology testing, respectively. CONCLUSIONS: This study showed that VE1 IHC should be a substitute for molecular biology in the initial assessment of the BRAFV600E status in MPP. This methodology needs to be set up in pathology laboratories in accordance with quality control/quality assurance accreditation procedures. Under these strict conditions the question is to know if BRAFV600E-IHC can serve not only as a prescreening tool, but also as a stand alone test (at least in cases displaying an unequivocally staining pattern) as well as an alternative predictive test for samples for which the molecular biology failed. PMID- 26377149 TI - Probing the molecular structures of plasma-damaged and surface-repaired low-k dielectrics. AB - Fully understanding the effect and the molecular mechanisms of plasma damage and silylation repair on low dielectric constant (low-k) materials is essential to the design of low-k dielectrics with defined properties and the integration of low-k dielectrics into advanced interconnects of modern electronics. Here, analytical techniques including sum frequency generation vibrational spectroscopy (SFG), Fourier transform infrared spectroscopy (FTIR), contact angle goniometry (CA) and X-ray photoelectron spectroscopy (XPS) have been employed to provide a comprehensive characterization of the surface and bulk structure changes of poly(methyl)silsesquioxane (PMSQ) low-k thin films before and after O2 plasma treatment and silylation repair. O2 plasma treatment altered drastically both the molecular structures and water structures at the surfaces of the PMSQ film while no bulk structural change was detected. For example, ~34% Si-CH3 groups were removed from the PMSQ surface, and the Si-CH3 groups at the film surface tilted toward the surface after the O2 plasma treatment. The oxidation by the O2 plasma made the PMSQ film surface more hydrophilic and thus enhanced the water adsorption at the film surface. Both strongly and weakly hydrogen bonded water were detected at the plasma-damaged film surface during exposure to water with the former being the dominate component. It is postulated that this enhancement of both chemisorbed and physisorbed water after the O2 plasma treatment leads to the degradation of low-k properties and reliability. The degradation of the PMSQ low-k film can be recovered by repairing the plasma-damaged surface using a silylation reaction. The silylation method, however, cannot fully recover the plasma induced damage at the PMSQ film surface as evidenced by the existence of hydrophilic groups, including C-O/C[double bond, length as m-dash]O and residual Si-OH groups. This work provides a molecular level picture on the surface structural changes of low-k materials after plasma treatment and the subsequent silylation repair. PMID- 26377148 TI - Investigation of Rho-Kinase Expressions and Polymorphisms in Mantle Cell Lymphoma Patients. AB - OBJECTIVE: Mantle cell lymphoma (MCL) is a rare but aggressive form of B-cell non Hodgkin lymphoma characterized by excessive expression of cyclin D1. Intracellular signaling enzyme Rho-kinase (ROCK) can contribute to cellular migration, proliferation, and differentiation, as well as tumor development and metastasis. However, ROCK gene and protein expressions or polymorphisms have never been investigated in MCL patients. The purpose of this study was to investigate the role of ROCK gene and protein expressions in MCL patients. We also examined ROCK2 gene polymorphisms in this study. MATERIALS AND METHODS: A total of 60 patients with MCL and 60 healthy controls were included in this retrospective study. Hematoxylin and eosin-stained lymph node tissue slides in the entire archive were reevaluated and used for immunohistochemistry, gene expression, and polymerase chain reaction studies. RESULTS: In immunohistochemical studies, there were significant increases in ROCK1 (p=0.0009) and ROCK2 (p<0.0001) protein expressions in MCL patients when compared with the control group. Although a marked increase in ROCK1 gene expression (p=0.0215) was noted, no significant change was observed in ROCK2 gene expression in MCL patients. Seven ROCK2 polymorphisms were studied, but the results showed no significant differences between the groups. CONCLUSION: This is the first study to show that ROCK1 gene and ROCK protein expressions may contribute to the development of MCL. PMID- 26377150 TI - Using an informed consent in mammography screening: a randomized trial. AB - Spanish women do not make an informed choice regarding breast cancer screening (BCS). Our aim was to evaluate the impact of receiving information regarding real BCS benefits and risks on knowledge, attitude, decision, feelings, and worries about cancer. Randomized controlled clinical trial of 355 women aged between 45 and 67 years, 177 and 178 assigned to the intervention group (IG) and control group (CG), respectively. After breast screening, women received either Nordic Cochrane Centre information on BCS or standard information. The primary outcome (knowledge) was determined from questionnaire administered at baseline and after a month. Answers were scored from 0 to 10 and scores of 5 or more indicated that women were well informed (had "good knowledge"). Questionnaires regarding attitudes, future screening intentions, and psychosocial impact were also administered. The Chi-squared and Student's t-tests were used to compare qualitative and quantitative variables, respectively. Good knowledge was acquired by 32 (18.10%) IG women and 15 (8.40%) CG women (P = 0.008). Mean scores from first to second interview increased from 2.97 (SD 1.16) to 3.43 (SD 1.39) in the CG and from and from 2.96 (SD 1.23) to 3.95 (SD 1.78) (P = 0.002) in the IG. No differences were found in the secondary endpoints. Women receiving information based on the Nordic Cochrane Centre document were better informed. This means of providing information is not very efficacious, nor does it modify attitude, decision, feelings, or worries about cancer. PMID- 26377151 TI - Neuroimaging of tic genesis: Present status and future perspectives. AB - Tics are hyperkinetic movements that are distinctive by their variety in semiology and duration and by their ability to be modulated by cognitive control. They are the hallmark of Gilles de la Tourette syndrome. Despite the variety of clinical presentations in this syndrome, dysfunction of cortico-striato-pallido thalamo-cortical networks is suggested as a core pathophysiological mechanism. We review recent structural and functional neuroimaging studies that focused on the anatomical substrate of tics and their possible genesis. These studies showed a consistent relationship between structural and functional abnormalities within motor cortico-basal ganglia circuits and occurrence of tics. The failure of top down cortical control over motor pathways because of the atypical trajectory of brain development could be a possible mechanism of tic genesis. Occurrence of tics results in several adaptive mechanisms, including modification of cortico striatal network activity (reduced functional activation of the primary motor cortex) and neurochemical (increased gamma-aminobutyric acid concentrations in the supplementary motor area) and microstructural white matter pathways rearrangements. PMID- 26377153 TI - Magnetic drug carriers: bright insights from light-responsive magnetic liposomes. PMID- 26377154 TI - Emerging trend of advanced image analysis in nanomedicine. PMID- 26377152 TI - Reproducibility of a Parkinsonism-related metabolic brain network in non-human primates: A descriptive pilot study with FDG PET. AB - BACKGROUND: We have previously defined a parkinsonism-related metabolic brain network in rhesus macaques using a high-resolution research positron emission tomography camera. This brief article reports a descriptive pilot study to assess the reproducibility of network activity and regional glucose metabolism in independent parkinsonian macaques using a clinical positron emission tomography/CT camera. METHODS: [(18)F]fluorodeoxyglucose PET scans were acquired longitudinally over 3 months in three drug-naive parkinsonian and three healthy control cynomolgus macaques. Group difference and test-retest stability in network activity and regional glucose metabolism were evaluated graphically, using all brain images from these macaques. RESULTS: Comparing the parkinsonian macaques with the controls, network activity was elevated and remained stable over 3 months. Normalized glucose metabolism increased in putamen/globus pallidus and sensorimotor regions but decreased in posterior parietal cortices. CONCLUSIONS: Parkinsonism-related network activity can be reliably quantified in different macaques with a clinical positron emission tomography/CT scanner and is reproducible over a period typically employed in preclinical intervention studies. This measure can be a useful biomarker of disease process or drug effects in primate models of Parkinson's disease. PMID- 26377159 TI - The Use of Low-Dose Recombinant Tissue Plasminogen Activator to Treat a Preterm Infant with an Intrauterine Spontaneous Arterial Thromboembolism. AB - Neonatal thromboembolic events are rare, and only a few cases of intrauterine spontaneous arterial thromboembolisms have been reported in the literature. Thrombolytic therapy with recombinant tissue plasminogen activator is usually the preferred treatment because it has a short half-life, fewer systemic side effects, and a strong, specific affinity for fibrin. Protocols vary from center to center, but there is still no consensus regarding the proper dosage or treatment duration. Herein, we present the case of an intrauterine spontaneous arterial thromboembolism in a preterm infant that completely resolved after being treated with low-dose recombinant tissue plasminogen activator (0.02 mg/kg/h). PMID- 26377158 TI - Strategies for improving the repair of focal cartilage defects. AB - Articular cartilage, together with skin, was predicted to be one of the first tissues to be successfully engineered. However cartilage repair remains nowadays still elusive, as we are still not able to overcome the hurdles of creating biomaterials corresponding to the native properties of the tissue, and which operate in joints environment that is not favorable for regeneration. In this review, we give an overview of the outcome of current cartilage treatment techniques. Furthermore we present current research strategies for improving cartilage tissue engineering. PMID- 26377165 TI - Revealing unusual chemical bonding in planar hyper-coordinate Ni2Ge and quasi planar Ni2Si two-dimensional crystals. AB - We discover unusual chemical bonding in a novel planar hyper-coordinate Ni2Ge free-standing 2D monolayer, and also in a nearly planar slightly buckled Ni2Si monolayer. This unusual bonding is revealed by Solid State Adaptive Natural Density Partitioning analysis. This analysis shows that a new type of 2c-2e Ni-Si sigma and 3c-2e Ni-Ge-Ni sigma bonds stabilize these 2D crystals. This is completely different from any previously known 2D crystals. Both of these free standing monolayers are global minima in two-dimensional space. Although their exotic structure has unprecedented chemical bonding, they show extraordinary stability as single layers. The stabilities of these frameworks are confirmed by phonon dispersion calculations and ab initio molecular dynamics calculations. For Ni2Si, the framework was maintained during short 10 ps molecular dynamics annealing up to 1500 K, while Ni2Ge survived 10 ps runs up to 900 K. Both systems are predicted to be non-magnetic and metallic. As these new 2D crystals contain hypercoordinated Group 14 atoms, they are examples of a new class of 2D crystals with unconventional chemical bonding and potentially exciting new properties. Interestingly, we find that the stabilities of Ni2Si and Ni2Ge are much higher than that of silicene and germanene. Thus, this work provides a novel way to stabilize 2D sheets of Group 14 elements. PMID- 26377156 TI - Double compartmented and hybrid implant outfitted with well-organized 3D stem cells for osteochondral regenerative nanomedicine. AB - AIM: Articular cartilage repair remains challenging, because most clinical failures are due to the lack of subchondral bone regeneration. We report an innovative approach improving cartilage repair by regenerating a robust subchondral bone, supporting articular cartilage. MATERIALS & METHODS: We developed a compartmented living implant containing triple-3D structure: stem cells as microtissues for embryonic endochondral development mimic, nanofibrous collagen to enhance mineralization for subchondral bone and alginate hydrogel for cartilage regeneration. RESULTS & CONCLUSION: This system mimics the natural gradient of the osteochondral unit, using only one kind of stem cell, targeting their ability to express specific bone or cartilage proteins. Mineralization gradient of articular cartilage and the natural 'glue' between subchondral bone and cartilage were reproduced in vitro. PMID- 26377157 TI - Bombesin-conjugated nanoparticles improve the cytotoxic efficacy of docetaxel against gastrin-releasing but androgen-independent prostate cancer. AB - AIM: Bombesin (BBN)-conjugated polymeric nanoparticles to target docetaxel (DTX) to prostate cancer cells that overexpress gastrin-releasing peptides receptors. MATERIALS & METHODS: In vitro cytotoxicity, uptake of nanoparticles and inhibition of cell migration were assessed against human prostate cancer cells. Preclinical pharmacokinetic and tissue-distribution studies of nanoparticles were performed in Balb/c mice and results compared with the marketed formulation Taxotere((r)). RESULTS: BBN-conjugated DTX-loaded nanoparticles exhibited higher cytotoxicity, inhibition of cell migration and colony formation than non-targeted nanoparticles or DTX alone. More BBN-conjugated nanoparticles were taken up at a faster rate than unconjugated nanoparticles. In vivo, this drug delivery improved pharmacokinetics of DTX by increasing mean residence time and decreasing clearance. CONCLUSION: This study provides an alternate approach for polysorbate free delivery of DTX, with improved in vivo performance. PMID- 26377155 TI - Codelivery of dual drugs from polymeric micelles for simultaneous targeting of both cancer cells and cancer stem cells. AB - AIM: Phenformin-loaded micelles (Phen M) were used in combination with gemcitabine-loaded micelles (Gem M) to study their combined effect against H460 human lung cancer cells and cancer stem cells (CSCs) in vitro and in vivo. MATERIALS & METHODS: Gem M and Phen M were prepared via self-assembly of a mixture of a diblock copolymer of PEG and urea-functionalized polycarbonate (PEG PUC) and a diblock copolymer of PEG and acid-functionalized polycarbonate (PEG PAC) through hydrogen bonding and ionic interactions. Gem M and Phen M were characterized and tested for efficacy both in vitro and in vivo against cancer cells and CSCs. RESULTS: The combination of Gem M/Phen M exhibited higher cytotoxicity against CSCs and non-CSCs than Gem M and Phen M alone, and showed significant cell cycle growth arrest in vitro. The combination therapy had superior tumor suppression and apoptosis in vivo without inducing toxicity to liver and kidney. CONCLUSION: The combination of Gem M and Phen M may be potentially used in lung cancer therapy. PMID- 26377163 TI - Identification of a dietary pattern prospectively associated with bone mass in Australian young adults. AB - BACKGROUND: Relatively little is known about the relations between dietary patterns and bone health in adolescence, which is a period of substantial bone mass accrual. OBJECTIVES: We derived dietary patterns that were hypothesized to be related to bone health on the basis of their protein, calcium, and potassium contents and investigated their prospective associations with bone mineral density (BMD), bone area, and bone mineral content (BMC) in a cohort of young adults. DESIGN: The study included 1024 young adults born to mothers who were participating in the Western Australian Pregnancy Cohort (Raine) Study. Dietary information was obtained from food-frequency questionnaires at 14 and 17 y of age. Dietary patterns were characterized according to protein, calcium, and potassium intakes with the use of reduced-rank regression. BMD, bone area, and BMC were estimated with the use of a total body dual-energy X-ray absorptiometry scan at 20 y of age. RESULTS: We identified 2 major dietary patterns. The first pattern was positively correlated with intakes of protein, calcium, and potassium and had high factor loadings for low-fat dairy products, whole grains, and vegetables. The second pattern was positively correlated with protein intake but negatively correlated with intakes of calcium and potassium and had high factor loadings for meat, poultry, fish, and eggs. After adjustment for anthropometric, sociodemographic, and lifestyle factors, a higher z score for the first pattern at 14 y of age was positively associated with BMD and BMC at 20 y of age [differences: 8.6 mg/cm(2) (95% CI: 3.0, 14.1 mg/cm(2)) and 21.9 g (95% CI: 6.5, 37.3 g), respectively, per SD increase in z score]. The z score for this same pattern at 17 y of age was not associated with bone outcomes at 20 y of age. The second pattern at 14 or 17 y of age was not associated with BMD, BMC, or bone area. CONCLUSIONS: A dietary pattern characterized by high intakes of protein, calcium, and potassium in midadolescence was associated with higher BMD and BMC at 20 y of age. Our results indicate that high consumption of low-fat dairy products, whole grains, and vegetables in adolescence are associated with beneficial effects on bone development. PMID- 26377164 TI - Comparison of cephalonium alone and in combination with an internal teat sealant for dry cow therapy in seasonally calving dairy cows. AB - AIM: To assess the effect of combining an internal teat sealant (ITS) and a long acting cephalonium-based dry cow therapy (DCT) on the prevalence of cows with a somatic cell count (SCC) >150,000 cells/mL 60-80 days after calving, and the incidence of clinical mastitis diagnosed by farm staff in the first 100 days after calving. METHODS: Cows from a spring-calving, pasture-based, dairy farm in the South Canterbury region of New Zealand were randomly allocated to receive cephalonium DCT (n=289) or cephalonium and internal teat sealant (n=304) at the end of lactation. Cows were inspected twice daily by farm staff during the dry period and following calving for signs of mastitis. Individual SCC were determined from herd tests conducted in the previous lactation and following calving. Logistic regression models were used to determine relationships with the prevalence of cows with a SCC >150,000 cells/mL after calving, and survival analysis was used to model time to the first case of clinical mastitis following calving at the cow and quarter level. RESULTS: The OR for a cow with a SCC >150,000 cells/mL after calving, including age and individual SCC in the preceding lactation in the model, was 0.53 (95% CI=0.32-0.89) for cows treated with combination therapy compared to cows receiving cephalonium (p=0.017). At the cow level, including age and preceding SCC in the model, the hazard ratio for diagnosis of clinical mastitis by farm staff in the first 100 days of lactation was 0.60 (95% CI=0.39-0.98) for cows treated with combination therapy compared to cows receiving cephalonium (p=0.04). At the quarter level, the hazard ratio for diagnosis of clinical mastitis, with age included in the model, was 0.41 (95% CI=0.23-0.74) for the combination therapy compared to cephalonium alone (p<0.001). CONCLUSIONS: The combination of internal teat sealant and cephalonium DCT was more effective than cephalonium alone at reducing clinical mastitis diagnosed by farm staff in the 100 days after calving, and the prevalence of cows with a SCC >150,000 cells/mL 60-80 days after calving. CLINICAL RELEVANCE: This study adds to the evidence that the prevention of intra mammary infections throughout the dry period and up to calving by using combination therapy is important in reducing the incidence of farmer-diagnosed clinical mastitis and prevalence of cows with a SCC >150,000 cells/mL 60-80 days after calving. PMID- 26377160 TI - Validity of the WHO cutoffs for biologically implausible values of weight, height, and BMI in children and adolescents in NHANES from 1999 through 2012. AB - BACKGROUND: The WHO cutoffs to classify biologically implausible values (BIVs) for weight, height, and weight-for-height in children and adolescents are widely used in data cleaning. OBJECTIVES: We assess 1) the prevalence of these BIVs, 2) whether they were consistent with information on waist circumference, arm circumference, and leg lengths, and 3) the effect of their exclusion on the estimated prevalence of obesity in 2- to 19-y-olds in the NHANES, which is a study in which extreme values were verified when recorded. DESIGN: We conducted cross-sectional analyses in 26,480 children and adolescents in the NHANES from 1999-2000 through 2011-2012. RESULTS: The overall prevalence for a BIV for any body-size measure was 0.9% (n = 277), and almost all BIVs were due to extremely high, rather than low, values. Of 186 subjects who had a high BIV for weight or body mass index (BMI), all but one subject had both arm and waist circumferences that were greater than the sex- and age-specific 95th percentiles; 75% of subjects had circumferences greater than the 99th percentile. Of 63 subjects with a high height BIV, 75% of them had a leg length that was greater than the 95th percentile. The exclusion of children and adolescents with a BIV reduced the overall prevalence of obesity by ~0.5 percentage points and by 1.7% in non Hispanic blacks. CONCLUSIONS: Most of the extremely high values of weight, height, and BMI flagged as BIVs in the NHANES are very likely correct. The increase of z score cutoffs or the use of an alternative method to detect possible errors could improve the balance between removing incorrect values and retaining extremely high, but accurate, values in other data sets. PMID- 26377162 TI - Omitting edema measurement: how much acute malnutrition are we missing? AB - BACKGROUND: Acute malnutrition is a major public health issue in low-income countries. It includes both wasting and edematous malnutrition, but the terms wasting and acute malnutrition are often used interchangeably. Little is known about the burden of edematous malnutrition, and few large-scale surveys measure it. OBJECTIVE: Most acute malnutrition might be captured by the measurement of wasting alone, but this is unknown. This article aims to fill this gap. DESIGN: This article presents a secondary data analysis of 852 nutrition cross-sectional survey data sets of children aged 6-59 mo. The data sets assembled included surveys from East, West, South, and Central Africa; the Caribbean; and Asia. The overlap between edematous malnutrition and wasting was assessed, and the impact of including/excluding edema on acute malnutrition prevalence estimates was evaluated. RESULTS: The prevalence of edematous malnutrition varied from 0% to 32.9%, and children were more likely to have bilateral edema in Central and South Africa (OR: 4; 95% CI: 2.8, 5.6). A large proportion of children with edematous malnutrition were not wasted [62% and 66% based on midupper arm circumference (MUAC) and weight-for-height (WFH), respectively], and most were not severely wasted (83% and 86% based on MUAC and WFH, respectively). When wasting and global acute malnutrition prevalence estimates as well as severe wasting and severe acute malnutrition prevalence estimates overall were compared, the differences between estimates were small (median of 0.0% and mean of 0.3% based on WFH and MUAC for global estimates and slightly higher median of 0.1% and mean of 0.4% based on MUAC and WFH, respectively, for the severe forms), but the picture was different at the regional level. CONCLUSIONS: The terms acute malnutrition and wasting should not be used interchangeably. The omission of the measurement of edema can have important repercussions, especially at the nutrition program level. PMID- 26377167 TI - Characterisation and Comparison of Acute Haemodynamic, Cardiac Biochemical and Hormonal Response to Different Ventricular Pacing Sites in the Normal Heart. AB - BACKGROUND: Acute cardiac response to right ventricular pacing is unknown. We aimed to assess the acute haemodynamic, biochemical and hormonal response to asynchronous right ventricular pacing and investigate whether there is a difference between an apical and outflow tract site. METHODS: In 21 patients with normal cardiac function, haemodynamics, brain natriuretic peptide and high sensitive troponin T were measured in response to 10minutes of pacing at each site in a randomised crossover fashion and compared. RESULTS: Pacing both sites there were significant increases in pulmonary capillary wedge pressures (p<0.001) and QRS width (p< 0.01). In comparison to baseline, apical pacing demonstrated significant (p<0.05) increases in arterial peptide and troponin levels and venous peptide levels. Outflow tract pacing compared to baseline demonstrated significant (p<0.05) increases in arterial peptide and venous, arterial and coronary sinus troponin. There were no significant differences in responses between sites. CONCLUSION: Asynchronous right ventricular pacing demonstrated significant increases in filling pressures, cardiac hormonal and biochemical response above baseline with very short durations of pacing (10minutes). There was no difference in response between sites. These findings imply that even very short periods of right ventricular based pacing are potentially deleterious. PMID- 26377161 TI - No increase in risk of hip fracture at high serum retinol concentrations in community-dwelling older Norwegians: the Norwegian Epidemiologic Osteoporosis Studies. AB - BACKGROUND: Norway has the highest hip fracture rates worldwide and a relatively high vitamin A intake. Increased fracture risk at high intakes and serum concentrations of retinol (s-retinol) have been observed in epidemiologic studies. OBJECTIVE: We aimed to study the association between s-retinol and hip fracture and whether high s-retinol may counteract a preventive effect of vitamin D. DESIGN: We conducted the largest prospective analysis of serum retinol and hip fracture to date in 21,774 men and women aged 65-79 y (mean age: 72 y) who attended 4 community-based health studies during 1994-2001. Incident hip fractures occurring up to 10.7 y after baseline were retrieved from electronic hospital discharge registers. Retinol determined by high-pressure liquid chromatography with ultraviolet detection in stored serum was available in 1154 incident hip fracture cases with valid body mass index (BMI) data and in a subcohort defined as a sex-stratified random sample (n = 1418). Cox proportional hazards regression weighted according to the stratified case-cohort design was performed. RESULTS: There was a modest increased risk of hip fracture in the lowest compared with the middle quintile of s-retinol (HR: 1.41; 95% CI: 1.09, 1.82) adjusted for sex and study center. The association was attenuated after adjustment for BMI and serum concentrations of alpha-tocopherol (HR: 1.16; 95% CI: 0.88, 1.51). We found no increased risk in the upper compared with the middle quintile. No significant interaction between serum concentrations of 25 hydroxyvitamin D and s-retinol on hip fracture was observed (P = 0.68). CONCLUSIONS: We found no evidence of an adverse effect of high serum retinol on hip fracture or any interaction between retinol and 25-hydroxyvitamin D. If anything, there tended to be an increased risk at low retinol concentrations, which was attenuated after control for confounders. We propose that cod liver oil, a commonly used food supplement in Norway, should not be discouraged as a natural source of vitamin D for fracture prevention. PMID- 26377168 TI - Chest Pain, Abnormal Electrocardiogram, High Troponins but Normal Coronary Angiography: Mystery Resolved by Cardiac Magnetic Resonance Imaging. PMID- 26377166 TI - Early farm residency and prevalence of asthma and hay fever in adults. AB - BACKGROUND: Asthma and hay fever have been found to be both positively and negatively associated with farming lifestyles in adulthood. Lack of congruency may depend upon early life exposure. OBJECTIVE: To assess the importance of different periods of farm residency for asthma and hay fever in an adult Canadian population. METHODS: We conducted a questionnaire survey in rural Saskatchewan, Canada. We assessed a history of asthma and hay fever with five categories of farm residency that were mutually exclusive: first year of life only, currently living on a farm, both first year of life and currently living on a farm, other farm living, and no farm living. Generalized estimating equations were used to adjust for clustering effects of adults within households. RESULTS: Of the 7148 responding, 30.6% had an early farm living experience only, 34.4% had both early and current farm living experiences, while 17.4% had never lived on a farm. The overall prevalence of ever asthma and hay fever was 8.6% and 12.3%, respectively, and was higher in women. Sex modified the associations between ever asthma and hay fever with farm residency variables whereby women had a decreased risk for both asthma [adjusted odds ratio (ORadj): 0.67, 95% confidence interval (CI):0.47 0.96] and hay fever (ORadj: 0.60, 95% CI: 0.44-0.83) with an early farm exposure only. Men currently living on a farm without an early farm exposure had an increased risk for ever asthma (ORadj: 1.82, 95% CI: 1.02-3.24). CONCLUSION: Farm residency in the first year of life shows a protective effect for adult asthma and hay fever that appears to differ by sex. PMID- 26377170 TI - Spontaneous regression of non-small cell lung cancer after biopsy of a mediastinal lymph node metastasis: a case report. AB - INTRODUCTION: Spontaneous regression of cancer is defined as a complete or partial, temporary or permanent disappearance of tumor in the absence of specific therapy. With only a few cases reported, spontaneous regression is extremely rare in primary lung cancer. Regarding spontaneous regression in lung cancer, recent investigations revealed the role of immunological mechanisms, thus indicating potential treatment options by specific immunotherapy in the future. CASE PRESENTATION: A 76-year-old Caucasian man with progressive dyspnea presented to our hospital. A computed tomography scan revealed a tumor mass in the upper lobe of his right lung and enlarged mediastinal lymph nodes. A biopsy of a paratracheal lymph node by mediastinoscopy disclosed metastatic lung cancer. By immunohistochemical findings the tumor was classified as large cell carcinoma. Diagnosed with clinical stage IIIA non-small cell lung cancer, a neoadjuvant therapy concept was indicated. However, before starting chemoradiation, a computed tomography scan showed a regression of both the tumor mass in the upper lobe of his right lung and the mediastinal lymphadenopathy. As a repeated computed tomography scan showed further regression, we agreed with our patient to perform routine follow-up instead of starting therapy. To date, no relapse has been reported. CONCLUSIONS: Given the circumstances that regression started after the biopsy and involved both the tumor in the upper lobe of his right lung and the mediastinal lymph node metastases, an immune response is a reasonable explanation for the observed spontaneous regression in this case. PMID- 26377171 TI - Notes on the reproductive biology of the Brazilian electric ray Narcine brasiliensis (Elasmobranchii: Narcinidae). AB - This study provides information on the reproductive biology of Narcine brasiliensis based on 105 individuals (72 females and 33 males) sampled in Sao Paulo State, Brazil. The total length at maturity for females was 318.9 mm and for males was 279.8 mm; pregnant females were observed only during summer and autumn. The peak of the gonado-somatic index for females and condition factor for males in the spring suggest a preparation for pregnancy and a mating period during this season. The capture of immature individuals indicates a need for management of the species in this region. PMID- 26377172 TI - Traumatic discitis due to pharyngeal needle aspiration. PMID- 26377175 TI - Right ventricular and atrial functions in patients with nonischemic dilated cardiomyopathy. AB - OBJECTIVE: The aim of this study was to assess the right ventricular and right atrial functions in patients with nonischemic dilated cardiomyopathy by novel echocardiographic measures. METHODS: In all, 40 patients with nonischemic dilated cardiomyopathy and 26 healthy subjects were consecutively included. Left ventricular, right ventricular, and right atrial functions were assessed by tissue Doppler imaging and two-dimensional speckle tracking echocardiography. Right ventricular systolic dysfunction was accepted moderated to severe when tissue Doppler peak systolic velocity of tricuspid lateral annulus was < 9 cm/s. RESULTS: In all, 18 of the 40 nonischemic dilated cardiomyopathy patients had peak systolic velocity of tricuspid lateral annulus < 9 cm/s and had significantly lower right ventricular free wall basal segment longitudinal strain, displacement, and right atrial functions assessed by speckle tracking echocardiography. Left ventricular tissue Doppler systolic velocity, global longitudinal and circumferential strain values were also lower in patients with moderated to severe right ventricular systolic dysfunction. Receiver operating characteristic analysis was preformed to assess the utility of right ventricular free wall basal segment longitudinal strain to predict right ventricular systolic dysfunction (peak systolic velocity < 9 cm/s). The cut off value for predicting right ventricular systolic dysfunction was - 20% with a sensitivity of 72% and specificity of 73% (AUC: 0.793; p = 0.002; 95% confidence interval: 0.645 0.941). CONCLUSIONS: Right ventricular systolic function is impaired in nonischemic dilated cardiomyopathy patients. Two-dimensional speckle tracking echocardiography represents a promising noninvasive method to evaluate right ventricular and atrial function in this patient group. PMID- 26377174 TI - Urinary enzymatic markers (N-acetyl-beta-D-glucosaminidase) in assessing the tubulointerstitial compartment in chronic glomerulonephritis related to odontogenic foci. AB - Chronic glomerulonephritis is related to focus infection. Odontogenic foci are frequently involved in glomerulonephritis. The relationship with the odontogenic focus infection can be demonstrated by the occurrence or aggravation of the symptoms of glomerulonephritis: proteinuria, haematuria, high blood pressure and oedema. Glomerular impairment in glomerulonephritis occurs together with inflammatory alterations of the tubulointerstitial compartment that can play an important part in the evolution of the disease. Tubular urinary markers can indicate the activation of this compartment during an infection of a focus, an odontogenic focus in our study.The paper aims at demonstrating the relationship between the odontogenic focus infection and tubulointerstitial lesions, assessed by a tubular urinary marker, N-acetyl beta-D glucosaminidase (NAG).We investigated the urinary N-acetyl beta-D glucosaminidase of 20 patients with chronic glomerulonephritis who presented odontogenic focus infections, comparing them with patients with chronic glomerulonephritis without odontogenic foci and of 20 controls, clinically healthy persons.Chronic glomerulonephritis patients with odontogenic focus infection presented clearly increased values as compared to clinically healthy control persons of urinary N-acetyl beta-D glucosaminidase.These patients underwent surgical intervention on the odontogenic focus under antibacterial prophylactic treatment. In 75% cases, the values of N acetyl beta-D glucosaminidase diminished, indicating the favourable effect of the treatment of the odontogenic focus on the tubulointerstitial compartment in patients with chronic glomerulonephritis. In 25% cases this therapeutic treatment was associated with an increase of the values of urinary N-acetyl beta-D glucosaminidase, expressing its unfavourable effect on chronic glomerulonephritis.Urinary N-acetyl beta-D glucosaminidase indicated an etiopathogenetic relationship between the odontogenic focus and the tubulointerstitial compartment in chronic glomerulonephritis. PMID- 26377169 TI - Defining the role of proton therapy in the optimal management of paediatric patients in Australia and New Zealand. AB - INTRODUCTION: Optimal management of paediatric patients with tumours may include radiation therapy. Proton therapy, in theory, should achieve superior outcomes. For children referred overseas, multiple factors are taken into consideration. AIM AND METHODS: The purpose of this article is to provide context to current decision making. The MEDLINE, EMBASE and PubMed databases were searched for relevant literature. RESULTS AND DISCUSSION: The delivery of proton therapy is in evolution. Tissue homogeneity, movement and anatomical changes all present a greater challenge for proton therapy compared with photon therapy. Many dosimetry studies are relying on historical data for cost-benefit analyses that do not accurately reflect contemporary photon therapy. The low dose regions generally do not create significant toxicity, whereas moderate dose regions can be reduced by different techniques such as stereotactic radiotherapy and brachytherapy. Neuro cognitive and neuro-endocrine toxicities are associated with the greatest health cost, so the greatest gain is for tumours within or abutting the central nervous system. Proton therapy does not eliminate the risk of second malignancy. CONCLUSIONS: The benefits of proton therapy must be weighed against not just the estimated impact of low and moderate radiation doses on the developing child but the disruptions to the child, and family life. Relative contraindications to proton therapy include when the relevant late toxicities relate to the high radiation dose region, when the tumour volumes encompass whole body sections and when the target is imprecise. Children with base of skull tumours or an inherited risk of cancer (e.g. those with p53 or Rb1 genes) should be considered for proton therapy. PMID- 26377178 TI - Association of hearing impairment with chronic kidney disease: a cross-sectional study of the Korean general population. AB - BACKGROUND: We aimed to evaluate the association between hearing impairment and the prevalence of chronic kidney disease (CKD) in the largest population-based cross-sectional study to date. METHODS: This cross-sectional study was based on the Korean National Health and Nutritional Examination Survey (KNHANES). It included 5226 participants >=19 years of age whose estimated glomerular filtration rate (eGFR) and hearing threshold had been measured. We diagnosed CKD as an eGFR <60 mL/min/1.73 m(2). The participants were also evaluated for the presence of other contributing factors related to kidney dysfunction. We divided the participants at the 40-dB threshold into hearing-impairment and no-hearing impairment groups, using the average threshold of all six frequencies (500, 1000, 2000, 3000, 4000, and 6000 Hz) for both ears. RESULTS: The odds of hearing impairment was 1.25 times higher (95 % confidence interval: 1.12-1.64, p-value < 0.001) in participants with an eGFR <60 mL/min/1.73 m(2) than in those with an eGFR >=60 mL/min/1.73 m(2) after adjustments for age, sex, smoking, alcohol, body mass index, diabetes mellitus, hypertension, dyslipidemia, and microalbuminuria. Among the risk parameters of CKD associated with hearing impairment, linear regression analysis adjusted for age and sex determined that each increase of serum creatinine or blood pressure was positively associated with an increase in hearing threshold (p-value < 0.01). CONCLUSION: The odds of hearing impairment were greater with lower eGFR than with normal eGFR. Individuals with CKD were more likely to also have hearing impairment. We recommend screening the hearing of patients with CKD to provide earlier identification of hearing impairment and earlier intervention, thereby preventing progression of hearing impairment and providing appropriate treatment strategies. PMID- 26377180 TI - Alistipes inops sp. nov. and Coprobacter secundus sp. nov., isolated from human faeces. AB - Culture-based study of the faecal microbiome in two adult female subjects revealed the presence of two obligately anaerobic, non-spore-forming, rod-shaped, non-motile, Gram-negative bacterial strains that represent novel species. The first strain, designated 627T, was a fastidious, slow-growing, indole-positive bacterium with a non-fermentative type of metabolism.The strain was characterized by the production of acetic and succinic acids as metabolic end products, the prevalence of iso-C15 : 0 fatty acid and the presence of menaquinones MK-10 and MK-11. The DNA G+C content was found to be 56.6 mol%. The second strain, designated 177T, was capable of fermenting a rich collection of carbohydrate substrates, producing acetic acid as a terminal product. The strain was indole negative and resistant to bile. The major cellular fatty acids were iso-C15 : 0 and anteiso-C15 : 0 (in a 1 : 1 ratio) and the predominant menaquinone was MK 11.The DNA G+C content was 37.8 mol%. A phylogenomic analysis of the draft genomes of strains 627T and 177T placed these bacteria in the genera Alistipes(family Rikenellaceae) and Coprobacter (family Porphyromonadaceae), respectively.On the basis of the phenotypic and genotypic properties of strains 627T and 177T, we conclude that these strains from human faeces represent two novel bacterial species, for which the names Alistipes inops sp. nov. (type strain 627T5DSM 28863T5VKM B-2859T) and Coprobacter secundus sp. nov. (type strain 177T=DSM 28864T=VKM B-2857T) are proposed. PMID- 26377183 TI - Apocrine Carcinoma of the Axilla Associated with Extramammary Paget's Disease: A Case Report and Review of the Literature. PMID- 26377173 TI - Deterioration of renal function at stent implantation can predict long-term outcome after stent thrombosis. AB - OBJECTIVES: The aim of the study was to examine the possible influence of minor deterioration of the renal function after stent implantation not fulfilling the criteria for acute kidney injury on long-term outcomes after stent thrombosis (ST). BACKGROUND: Decreased renal function (DRF) is associated with an increased risk for worse outcome after percutaneous coronary intervention. There is no data if the deterioration of renal function after stent implantation influences the prognosis after ST. If so patients with a higher risk for worse outcome after ST could be identified already at the time of stent implantation. METHODS: Data from 4824 consecutive patients treated with percutaneous coronary intervention in our center was recorded from March 2004 to April 2010. We excluded patients with acute kidney injury at stent implantation and 86 of them with ST without acute kidney injury at stent implantation were involved in the study. They were prospectively followed until December 2012 for 50.2 +/- 28.1 months. Only patients with definite ST were included in the study. The Academic Research Consortium definition of ST was used. Data on death, myocardial infarction, and repeated percutaneous or operative revascularization after ST were ascertained from the hospital database, by phone or with clinical examinations. The outcomes after definite ST were compared in patients with and without deterioration of renal function after stent implantation (DRFafterSI). RESULTS: During the observational period patients with DRFafterSI had a higher mortality rate after ST than patients without DRFafterSI (35.1 vs. 10.3 %; p <0.019). The incidence of major adverse cardiac events (major adverse coronary event (MACE)-death, myocardial infarction, repeated revascularization) rate after ST was similar in both groups (66.1 % with DRFafterSI vs. 55.2 % without DRFafterSI). The prevalence of myocardial infarction was also similar in both groups (31.6 vs. 34.5 %) as was the revascularizations rate (43.9 vs. 48.3 %). Death was predicted by DRFafterSI (adjusted hazard ratio (HR) 3.96; 95 % confidence interval (CI) 1.11 to 14.10; p <0.034) and age > 75 years (adjusted HR 2.85: 95 % CI 1.12-7.30; p = 0.029). We could not find any predictor for MACE. CONCLUSIONS: Even more subtle DRFafterSI (not fulfilling the criteria for acute kidney injury) at stent implantation were associated with higher long-term mortality after ST. Especially at risk were patients older than 75 years at stent implantation. DRFafterSI and age more than 75 years pointed out the group of patients with a high risk for death after ST already at the time of stent implantation. The best treatment option for preventing ST in these patients is still to be determined. Until then, we must pay a special attention to proper patients' preparation and hydration to avoid DRFafterSI. PMID- 26377179 TI - In silico identification of bacteriocin gene clusters in the gastrointestinal tract, based on the Human Microbiome Project's reference genome database. AB - BACKGROUND: The human gut microbiota comprises approximately 100 trillion microbial cells which significantly impact many aspects of human physiology - including metabolism, nutrient absorption and immune function. Disturbances in this population have been implicated in many conditions and diseases, including obesity, type-2 diabetes and inflammatory bowel disease. This suggests that targeted manipulation or shaping of the gut microbiota, by bacteriocins and other antimicrobials, has potential as a therapeutic tool for the prevention or treatment of these conditions. With this in mind, several studies have used traditional culture-dependent approaches to successfully identify bacteriocin producers from the mammalian gut. In silico-based approaches to identify novel gene clusters are now also being utilised to take advantage of the vast amount of data currently being generated by next generation sequencing technologies. In this study, we employed an in silico screening approach to mine potential bacteriocin clusters in genome-sequenced isolates from the gastrointestinal tract (GIT). More specifically, the bacteriocin genome-mining tool BAGEL3 was used to identify potential bacteriocin producers in the genomes of the GIT subset of the Human Microbiome Project's reference genome database. Each of the identified gene clusters were manually annotated and potential bacteriocin-associated genes were evaluated. RESULTS: We identified 74 clusters of note from 59 unique members of the Firmicutes, Bacteroidetes, Actinobacteria, Fusobacteria and Synergistetes. The most commonly identified class of bacteriocin was the >10 kDa class, formerly known as bacteriolysins, followed by lantibiotics and sactipeptides. CONCLUSIONS: Multiple bacteriocin gene clusters were identified in a dataset representative of the human gut microbiota. Interestingly, many of these were associated with species and genera which are not typically associated with bacteriocin production. PMID- 26377176 TI - Impaired coronary blood flow may be related to elevated homocysteine levels in patients with metabolic syndrome. AB - BACKGROUND: Metabolic syndrome (MS) refers to a group of cardiovascular risk factors associated with endothelial dysfunction and impaired coronary blood flow (CBF). Homocysteine (Hcy) is another risk factor for the development of insulin resistance and endothelial dysfunction. However, the relationship between Hcy levels and CBF in patients with MS has not been investigated specifically. In the present study, we aimed to evaluate the relationship between Hcy levels and CBF in MS patients with normal coronary arteries. METHODS: The study population included 36 patients with MS (20 males, 16 females; mean age = 55 +/- 9 years) and 36 control subjects (20 males, 16 females; mean age = 51 +/- 7 years). All subjects had angiographically proven normal coronary arteries. Plasma Hcy concentrations were evaluated after a fast of 12 h or longer. The CBF rates of all subjects were documented by the thrombolysis in myocardial infarction (TIMI) frame count method. RESULTS: The TIMI frame counts for each major epicardial coronary artery and mean TIMI frame count were found to be significantly higher in the MS group compared with the control group (left anterior descending coronary artery (LAD): 53 +/- 26 vs. 39 +/- 17; p = 0.01, left circumflex artery (LCx): 32 +/- 12 vs. 26 +/- 11; p = 0.01, right coronary artery (RCA): 33 +/- 14 vs. 26 +/- 12; p = 0.02, mean TIMI frame count: 39 +/- 16 vs. 20 +/- 12; p = 0.01). Plasma Hcy levels in patients with MS were significantly higher compared with controls (MS group = 11.6 +/- 4 and control group = 9.6 +/- 2.6; p = 0.01). Additionally, plasma Hcy levels were positively correlated with each calculated TIMI frame count value in the MS group (LAD, r: 0.28 and p = 0.006; LCx, r: 0.25 and p = 0.022; RCA, r: 0.26 and p = 0.042; mean TIMI frame count, r: 0.28 and p = 0.004). CONCLUSION: Plasma Hcy levels and TIMI frame counts were significantly higher in patients with MS. Impaired CBF in MS may be related to elevated levels of Hcy, even if Hcy levels are normal. PMID- 26377181 TI - Development and validation of a questionnaire to evaluate lifestyle-related behaviors in elementary school children. AB - BACKGROUND: The SI! Program promotes cardiovascular health through a multilevel school-based intervention on four lifestyle-related components: diet, physical activity, understanding the body and heart, and management of emotions. We report here the development and validation of the KAH (knowledge, attitudes and habits) questionnaire adapted for elementary school children (6-7 years old) as a tool for the forthcoming evaluation of the SI! Program, where the KAH scoring will be the primary outcome. The efficacy of such an intervention will be based on the improvements in children's KAH towards a healthy lifestyle. METHODS: The questionnaire validation process started with a pool of items proposed by the pedagogical team who developed the SI! Program for elementary school. The questionnaire was finalized by decreasing the number of items from 155 to 48 using expert panels and statistical tests on the responses from 384 children (ages 6-7). A team of specialized psychologists administered the questionnaire at schools providing standard directions for the final administration. The internal consistency was assessed using Cronbach's alpha coefficients. Reliability was measured through the split-half method, and problematic items were detected applying the item response theory. Analysis of variance and Tukey's test of additivity were used for multiple comparisons. RESULTS: The final KAH questionnaire for elementary school children should be administered to children individually by trained staff. The 48 items-questionnaire is divided evenly between the 4 components of the intervention, with an overall Cronbach's alpha = 0.791 (alpha = 0.526 for diet, alpha = 0.537 for physical activity, alpha = 0.523 for human body and heart, and alpha = 0.537 for management of emotions). CONCLUSIONS: The KAH-questionnaire is a reliable instrument to assess the efficacy of the SI! Program on instilling healthy lifestyle-related behaviors in elementary school children. PMID- 26377185 TI - Dopamine agonist inhibits vascular endothelial growth factor protein production and secretion in granulosa cells. AB - BACKGROUND: Dopamine receptor 2 agonists (D2-ags) inhibit vascular endothelial growth factor (VEGF) secretion in luteinized granulosa cells (LGCs) both in vitro and in vivo. However, the mechanism of D2 regulation of the VEGF/VEGF Receptor 2 (VEGFR-2) pathway remains to be elucidated. We sought to determine the effects of D2 signaling on VEGF transcription and translation in LGCs, with the expectation of identifying potential D2-ag-based therapies for ovarian hyperstimulation syndrome (OHSS). FINDINGS: LGCs from egg donors were cultured with chorionic gonadotropin (hCG) in the presence of Actinomycin-D (ActD) or Brefeldin-A (BFA) to evaluate the effects of a D2-ag, cabergoline (Cb2), on VEGF secretion. The contribution of the conventional Gi/Go, Gz and AKT/beta-Arrestin pathways in the VEGF regulation was assessed by adding pertussis toxin (PTX), phorbol 12 myristate 13-acetate (PMA), or wortmannin (WT). While Cb2 inhibited VEGF secretion by interfering with VEGF peptide translation and secretion, inhibition of conventional D2 transduction pathways did not reverse Cb2-mediated inhibition of VEGF secretion. CONCLUSIONS: The effects of D2-ag on VEGF translation and secretion are mediated by D2 signaling pathways that have yet to be described. We found that D2-ag inhibits VEGF secretion at the post-transcriptional level, suggesting that D2-ag treatment should be combined with therapies that inhibit VEGF transcription, such as the employment of LH or GnRH for triggering ovulation, to improve the efficacy of OHSS prevention. PMID- 26377177 TI - Yersinia pestis uses the Ail outer membrane protein to recruit vitronectin. AB - Yersinia pestis, the agent of plague, requires the Ail (attachment invasion locus) outer membrane protein to survive in the blood and tissues of its mammalian hosts. Ail is important for both attachment to host cells and for resistance to complement-dependent bacteriolysis. Previous studies have shown that Ail interacts with components of the extracellular matrix, including fibronectin, laminin and heparan sulfate proteoglycans, and with the complement inhibitor C4b-binding protein. Here, we demonstrate that Ail-expressing Y. pestis strains bind vitronectin - a host protein with functions in cell attachment, fibrinolysis and inhibition of the complement system. The Ail-dependent recruitment of vitronectin resulted in efficient cleavage of vitronectin by the outer membrane Pla (plasminogen activator protease). Escherichia coli DH5alpha expressing Y. pestis Ail bound vitronectin, but not heat-treated vitronectin. The ability of Ail to directly bind vitronectin was demonstrated by ELISA using purified refolded Ail in nanodiscs. PMID- 26377186 TI - De novo production of six key grape aroma monoterpenes by a geraniol synthase engineered S. cerevisiae wine strain. AB - BACKGROUND: Monoterpenes are important contributors to grape and wine aroma. Moreover, certain monoterpenes have been shown to display health benefits with antimicrobial, anti-inflammatory, anticancer or hypotensive properties amongst others. The aim of this study was to construct self-aromatizing wine yeasts to overproduce de novo these plant metabolites in wines. RESULTS: Expression of the Ocimum basilicum (sweet basil) geraniol synthase (GES) gene in a Saccharomyces cerevisiae wine strain substantially changed the terpene profile of wine produced from a non-aromatic grape variety. Under microvinification conditions, and without compromising other fermentative traits, the recombinant yeast excreted geraniol de novo at an amount (~750 MUg/L) well exceeding (>10-fold) its threshold for olfactory perception and also exceeding the quantities present in wines obtained from highly aromatic Muscat grapes. Interestingly, geraniol was further metabolized by yeast enzymes to additional monoterpenes and esters: citronellol, linalool, nerol, citronellyl acetate and geranyl acetate, resulting in a total monoterpene concentration (~1,558 MUg/L) 230-fold greater than that of the control. We also found that monoterpene profiles of wines derived from mixed fermentations were found to be determined by the composition of the initial yeast inocula suggesting the feasibility of producing 'a la carte' wines having predetermined monoterpene contents. CONCLUSIONS: Geraniol synthase-engineered yeasts demonstrate potential in the development of monoterpene enhanced wines. PMID- 26377187 TI - Arterial Embolisms and Thrombosis in Upper Extremity Ischemia. AB - OBJECTIVE: Upper extremity ischemia (UEI) is an uncommon condition that can lead to permanent disability. There is a limited understanding of the etiology, management, and outcomes of the disease. METHODS: We retrospectively reviewed the charts of all patients who were diagnosed with "embolism and/or thrombosis of arteries of upper extremity" at our institution from January 2005 to December 2013. RESULTS: Patients diagnosed with embolisms were older (P < .001), more likely to undergo thromboembolectomy (P < .001), had higher rates of hypertension (P = .001), and had longer lengths of hospital stay (P = .002). There were no significant differences in complications or mortality at 30 days and up to 1 year. CONCLUSION: At our center, embolism was found to be the most common etiology for UEI followed by thrombosis and stenosis. Patients presented with embolism were older, were more likely to undergo thromboembolectomy, and had higher rates of hypertension and longer hospital stays. PMID- 26377182 TI - Clinical and environmental genotypes of Vibrio vulnificus display distinct, quorum-sensing-mediated, chitin detachment dynamics. AB - The ability for bacteria to attach to and detach from various substrata is important for colonization, survival and transitioning to new environments. An opportunistic human pathogen, Vibrio vulnificus, can cause potentially fatal septicemia after ingestion of undercooked seafood. Based on genetic polymorphisms, strains of this species are subtyped into clinical (C) and environmental (E) genotypes. Vibrio vulnificus readily associates with chitin, thus we investigated chitin detachment dynamics in these disparate genotypes. We found that C-genotypes detach significantly more than E-genotypes after 24 hours in aerobic as well as anaerobic conditions. Furthermore, expression of genes involved in type IV pilin production was significantly downregulated in C genotypes compared to E-genotypes, suggesting an importance in detachment. Interestingly, gbpA, a gene that has been shown to be important in host colonization in V. cholerae, was upregulated in the C-genotypes during detachment. Additionally, we found that C-genotypes detached to a greater extent, and produced more quorum-sensing (QS) autoinducer-2 molecules relative to E genotypes, which suggests a role for QS in detachment. These findings suggest that for V. vulnificus, QS-mediated detachment may be a potential mechanism for transitioning into a human host for C-genotypes, while facilitating E-genotype maintenance in the estuarine environment. PMID- 26377184 TI - 'Medusa head ataxia': the expanding spectrum of Purkinje cell antibodies in autoimmune cerebellar ataxia. Part 2: Anti-PKC-gamma, anti-GluR-delta2, anti Ca/ARHGAP26 and anti-VGCC. AB - Serological testing for anti-neural autoantibodies is important in patients presenting with idiopathic cerebellar ataxia, since these autoantibodies may indicate cancer, determine treatment and predict prognosis. While some of them target nuclear antigens present in all or most CNS neurons (e.g. anti-Hu, anti Ri), others more specifically target antigens present in the cytoplasm or plasma membrane of Purkinje cells (PC). In this series of articles, we provide a detailed review of the clinical and paraclinical features, oncological, therapeutic and prognostic implications, pathogenetic relevance, and differential laboratory diagnosis of the 12 most common PC autoantibodies (often referred to as 'Medusa head antibodies' due their characteristic somatodendritic binding pattern when tested by immunohistochemistry). To assist immunologists and neurologists in diagnosing these disorders, typical high-resolution immunohistochemical images of all 12 reactivities are presented, diagnostic pitfalls discussed and all currently available assays reviewed. Of note, most of these antibodies target antigens involved in the mGluR1/calcium pathway essential for PC function and survival. Many of the antigens also play a role in spinocerebellar ataxia. Part 1 focuses on anti-metabotropic glutamate receptor 1 , anti-Homer protein homolog 3-, anti-Sj/inositol 1,4,5-trisphosphate receptor- and anti-carbonic anhydrase-related protein VIII-associated autoimmune cerebellar ataxia (ACA); part 2 covers anti-protein kinase C gamma-, anti-glutamate receptor delta-2-, anti-Ca/RhoGTPase-activating protein 26- and anti-voltage-gated calcium channel-associated ACA; and part 3 reviews the current knowledge on anti-Tr/delta notch-like epidermal growth factor-related receptor-, anti-Nb/AP3B2-, anti Yo/cerebellar degeneration-related protein 2- and Purkinje cell antibody 2 associated ACA, discusses differential diagnostic aspects, and provides a summary and outlook. PMID- 26377188 TI - Open Versus Endovascular Repair of Inflammatory Abdominal Aortic Aneurysms: A Comparative Study and Meta-Analysis of the Literature. AB - OBJECTIVES: Open surgical repair (OSR) of inflammatory abdominal aortic aneurysms (IAAAs) can have significant morbidity. The aim of the present investigation was to compare IAAA outcome after OSR and endovascular aneurysm repair (EVAR) and perform a meta-analysis of the literature. METHODS: Twenty-seven patients with an intact IAAA operated on during a 21-year period were included. RESULTS: Nine patients were managed with EVAR and 18 with OSR. In the EVAR group, the number of transfused red blood cell units (P = .001), procedure duration (P < .001), and postoperative hospitalization (P = .004) were significantly reduced compared to OSR. A trend for decreased morbidity with EVAR (11% vs 33% for OSR, P = .36) was observed. On literature review and meta-analysis, morbidity after EVAR was 8.3%, significantly lower compared to OSR (27.4%, P = .047). Mortality for nonruptured IAAAs was 0% after EVAR and 3.6% after OSR (P = 1.00). CONCLUSIONS: Endovascular aneurysm repair of IAAAs is associated with decreased procedure duration, transfusion needs, hospitalization, and morbidity compared to OSR. PMID- 26377189 TI - Measuring abortion-related mortality: challenges and opportunities. AB - Two recent efforts to quantify the causes of maternal deaths on a global scale generated divergent estimates of abortion-related mortality. Such discrepancies in estimates of abortion-related mortality present an important opportunity to explore unique challenges and opportunities associated with the generation and interpretation of abortion-related mortality estimates. While innovations in primary data collection and estimation methodologies are much needed, at the very least, studies that seek to measure maternal deaths due to abortion should endeavor to improve transparency, acknowledge limitations of data, and contextualize results. As we move towards sustainable development goals beyond 2015, the need for valid and reliable estimates of abortion-related mortality has never been more pressing. The post-MDG development agenda that aims to improve global health, reduce health inequities, and increase accountability, requires new and novel approaches be tested to improve measurement and estimation of abortion-related mortality, as well as incidence, safety and morbidity. PMID- 26377190 TI - Engaging rural women in healthy lifestyle programs: insights from a randomized controlled trial. AB - BACKGROUND: The obesity epidemic is well established, particularly in rural settings. Programs promoting healthy lifestyles for rural women are urgently needed; however, participant engagement is challenging. In the context of a large randomized controlled trial targeting the prevention of weight gain in rural women, we explored successful recruitment strategies and aimed to understand participants' barriers, enablers and reasons for program participation. METHODS: We recruited women (aged 18-55 years) from the general rural Australian population. A mixed-methods approach was applied to explore factors that influenced program participation, including quantitative questionnaires for all participants (n = 649) and qualitative semi-structured interviews conducted for a subgroup of participants (n = 45). Data were collected at three time points: baseline, 6 and 12 months post program commencement. RESULTS: We recruited 649 rural women through a community communication and partnering strategy, a program marketing campaign and mobilization of social networks. Program participants were diverse across education and income levels and were representative of the wider Australian regional population. Factors that influenced program engagement were divided into personal (perceived program benefits and program accessibility) and social (peer persuasion and support). Identified enablers included convenience of the program location, perceived program utility, such as weight management and optimization of lifestyle choices, as well as attending the program with peer support. Barriers to engagement, which are likely exacerbated in rural communities included lack of anonymity, self-consciousness and segregated social networks in rural settings. Participants reported that eliciting local support and maximizing publicity is fundamental to improving future program engagement. CONCLUSION: Multiple program promotion strategies including communication, marketing and partnering, as well as mobilization of social networks and peer persuasion, enabled engagement of rural women into a healthy lifestyle program. These recruitment strategies are consistent with successful strategies utilized previously to recruit urban-dwelling women into lifestyle programs. Future engagement efforts in rural settings could be enhanced by hosting multiple sessions within existing socio-cultural networks and assuring participants that they will not need to share their personal health information with others in their community. TRIAL REGISTRATION: Australia & New Zealand Clinical Trial Registry. Trial number ACTRN12612000115831. Date of registration 24 January 2012. PMID- 26377191 TI - A case report of a rare intramuscular granular cell tumor. AB - BACKGROUND: Granular cell tumors (GCTs) were firstly described by Weber in 1854 and 70 years later by Abrikossoff and classified as benign tumors. Originally considered muscle tumors, they have been identified as neural lesions, due to their close association with nerve and to their immunohystochemical characteristics. GCTs are uncommon tumors and they may arise in any part of the body; they have been mainly observed in tongue, chest wall and upper extremities; less frequent sites are larynx, gastrointestinal tract, breast, pituitary stalk and the female anogenital region. Here we report a case of GCT showing an uncommon localization such as the upper third of the right rectus muscle of the abdominal wall. CASE PRESENTATION: A 45 year-old woman of Caucasian origin presented to the surgeon with a 6-month history of light pain in the upper third of the abdominal wall. Radiological exams (Ultrasonography, Computed Tomography and Contrast magnetic resonance imaging) showed a localized in the right rectus abdominis muscle. After excision, histological and immunohystochemical analysis, with the support of electron microscopy, allowed making diagnosis of granular cell tumor. DISCUSSION: After fist description by Abrikosoff in 1926 of GCT like mesenchymal tumor of unknown origin, in recent years immunohystochemical techniques definitely demonstrated the histogenetic derivation of GCT from Schwann cells. Granular cell tumors are rare, small, slow-growing, solitary and painless subcutaneous nodules which behave in a benign fashion, but can have a tendency to recur; in rare cases they can metastasize, when they became malignant; there are some clinical and histological criteria to suspect the malignance of this tumor. CONCLUSION: It is important that clinicians, radiologists and pathologists are aware of the clinical presentation and histopathology of GCT for appropriate management, counselling and follow-up. In our case we had a complete radiological, morphological and immunohystochemical characterization of the lesion and a definitive diagnosis of benignity confirmed by electron microscopy. PMID- 26377192 TI - Trajectories of depressive symptoms following breast cancer diagnosis. AB - BACKGROUND: This longitudinal study sought to identify groups of breast cancer survivors exhibiting distinct trajectories of depressive symptoms up to 24 months following diagnosis, and to describe characteristics associated with these trajectories. METHODS: A total of 653 women completed baseline questionnaires within 8 months of breast cancer diagnosis on patient characteristics, symptoms, and psychosocial variables. Depressive symptoms were assessed at baseline and 6, 12, and 18 months after baseline. Chart reviews provided cancer and treatment related data. Finite mixture modeling identified trajectories of depressive symptoms measured with the Beck Depression Inventory (BDI). RESULTS: Six distinct trajectories were identified. Just over half of the sample had consistently very low (3.8%) or low (47.3%) BDI scores well below the traditional BDI cutoff point of 10 thought to be indicative of clinically significant depression; 29.2% had consistently borderline scores; 11.3% had initially high scores that declined over time, but remained above the cutoff point; 7.2% showed increased BDI over time; and a small but unique group (1.1%) reported chronically high scores above 25. Women in groups with lower depressive symptom levels were older, had less rigorous chemotherapy, fewer physical symptoms (fatigue and pain), and lower levels of illness intrusiveness. CONCLUSIONS: Approximately 20% of women had levels of depressive symptoms indicative of clinical depression that were maintained 2 years postdiagnosis. Factors related to trajectory membership such as illness intrusiveness, social support, fatigue, pain, and vasomotor symptoms suggest targets for possible intervention. IMPACT: Results demonstrate the heterogeneity of depressive symptoms following breast cancer and the need for continued screening posttreatment. PMID- 26377194 TI - Differential inequality trends over time in survival among U.S. children with acute lymphoblastic leukemia by race/ethnicity, age at diagnosis, and sex. AB - BACKGROUND: It is unclear how inequalities in survival among children with acute lymphoblastic leukemia (ALL) have changed over time in different race/ethnicity groups. METHODS: Children diagnosed with a first primary malignant ALL at ages 0 to 19 years in 1975-2010 in the nine Surveillance, Epidemiology, and End Results cancer registries were included. Cumulative ALL mortalities were compared, and multivariable Cox regression analyses were applied to estimate ALL mortality HRs associated with race/ethnicity, age at diagnosis, and sex, adjusting for each other, within each diagnosis period (1975-1983, 1984-1991, 1992-1999, and 2000 2010). RESULTS: Compared with non-Hispanic-whites (NH-whites), the HR in non Hispanic-blacks (NH-blacks) dropped to 1.21 [95% confidence interval (CI), 0.74 1.96] in 2000-2010 from the largest inequality in 1984-1991 (HR, 2.09; 95% CI, 1.57-2.79); the HR in Hispanics increased, however, from 1.28 (95% CI, 0.98-1.66) in 1975-1983 to 1.95 (95% CI, 1.48-2.58) in 2000-2010. Asian/Pacific Islanders (API) and American Indian/Alaska Natives (AIAN) had HRs of 1.39 (95% CI, 0.92 2.11) and 2.31 (95% CI, 1.13-4.74), respectively, in 2000-2010 with nonstatistically significant increases over time. In 2000-2010, compared with NH white counterparts, NH-blacks and APIs diagnosed at 1-9 years, Hispanics diagnosed at 1-9 and 10-19 years, and AIANs diagnosed at 10-19 years all had about twice the ALL mortality hazard rates; inequality was observed among API boys (HR, 1.61; 95% CI, 1.00-2.60) but not API girls. CONCLUSIONS: Survival inequalities changed differently across subgroups of children with ALL. IMPACT: Underlying causes of the differential trends need to be examined, such that targeted interventions can be developed to reduce inequalities. PMID- 26377193 TI - A newly identified susceptibility locus near FOXP1 modifies the association of gastroesophageal reflux with Barrett's esophagus. AB - BACKGROUND: Important risk factors for esophageal adenocarcinoma and its precursor, Barrett's esophagus, include gastroesophageal reflux disease, obesity, and cigarette smoking. Recently, genome-wide association studies have identified seven germline single-nucleotide polymorphisms (SNP) that are associated with risk of Barrett's esophagus and esophageal adenocarcinoma. Whether these genetic susceptibility loci modify previously identified exposure-disease associations is unclear. METHODS: We analyzed exposure and genotype data from the BEACON Consortium discovery phase GWAS, which included 1,516 esophageal adenocarcinoma case patients, 2,416 Barrett's esophagus case patients, and 2,187 control participants. We examined the seven newly identified susceptibility SNPs for interactions with body mass index, smoking status, and report of weekly heartburn or reflux. Logistic regression models were used to estimate ORs for these risk factors stratified by SNP genotype, separately for Barrett's esophagus and esophageal adenocarcinoma. RESULTS: The odds ratio for Barrett's esophagus associated with at least weekly heartburn or reflux varied significantly with the presence of at least one minor allele of rs2687201 (nominal P = 0.0005, FDR = 0.042). ORs (95% CIs) for weekly heartburn or reflux among participants with 0, 1, or 2 minor alleles of rs2687201 were 6.17 (4.91-7.56), 3.56 (2.85-4.44), and 3.97 (2.47-6.37), respectively. No statistically significant interactions were observed for smoking status and body mass index. CONCLUSION: Reflux symptoms are more strongly associated with Barrett's esophagus risk among persons homozygous for the major allele of rs2687201, which lies approximately 75 kb downstream of the transcription factor gene FOXP1. IMPACT: The novel gene-exposure interaction discovered in this study provides new insights into the etiology of esophageal adenocarcinoma. PMID- 26377196 TI - Concept for quantifying the dose from image guided radiotherapy. AB - BACKGROUND: Radiographic image guidance is routinely used for patient positioning in radiotherapy. All radiographic guidance techniques can give a significant radiation dose to the patient. The dose from diagnostic imaging is usually managed by using effective dose minimization. In contrast, image-guided radiotherapy adds the imaging dose to an already high level of therapeutic radiation which cannot be easily managed using effective dose. The purpose of this work is the development of a concept of IGRT dose quantification which allows a comparison of imaging dose with commonly accepted variations of therapeutic dose. METHODS: It is assumed that dose variations of the treatment beam which are accepted in the spirit of the ALARA convention can also be applied to the additional imaging dose. Therefore we propose three dose categories: Category I: The imaging dose is lower than a 2% variation of the therapy dose. Category II: The imaging dose is larger than in category I, but lower than the therapy dose variations between different treatment techniques. Category III: The imaging dose is larger than in Category II. For various treatment techniques dose measurements are used to define the dose categories. The imaging devices were categorized according to the measured dose. RESULTS: Planar kV-kV imaging is a category I imaging procedure. kV-MV imaging is located at the edge between category I and II and is for increasing fraction size safely a category I imaging technique. MV-MV imaging is for all imaging technologies a category II procedure. MV fan beam CT for localization is a category I technology. Low dose protocols for kV CBCT are located between category I and II and are for increasing fraction size a category I imaging technique. All other investigated Pelvis-CBCT protocols are category II procedures. Fan beam CT scout views are category I technology. Live imaging modalities are category III for conventional fractionation, but category II for stereotactic treatments. CONCLUSIONS: Dose from radiotherapy imaging can be categorized in terms of generally accepted dose variations of therapy dose. This concept allows the quantification of daily dose from image guided radiotherapy in the spirit of the ALARA convention. PMID- 26377195 TI - Metformin use and risk of colorectal adenoma after polypectomy in patients with type 2 diabetes mellitus. AB - BACKGROUND: Existing literature suggests that metformin, the most commonly used biguanide, may lower colorectal cancer risk. Because most colorectal cancers originate in precancerous adenomas, we examined whether metformin use lowered colorectal adenoma risk after polypectomy in patients with type-2 diabetes. METHODS: Retrospective cohort study of 40- to 89-year-old Kaiser Permanente Northern California patients who had type 2 diabetes, and >=1 adenoma detected at baseline colonoscopy during 2000 to 2009 and a repeat colonoscopy 1 to 10 years from baseline adenoma diagnosis through 2012. Cox models evaluated the association between metformin use during follow-up and subsequent adenoma diagnoses, controlling for age, race/ethnicity, sex, body mass index, and repeat examination indication. RESULTS: Study included 2,412 patients followed for a median of 4.5 years; cumulatively, 1,117 (46%) patients had >=1 adenoma at repeat colonoscopy. Compared with patients not receiving diabetes medications (n = 1,578), metformin-only use (n = 457) was associated with lower adenoma recurrence risk [adjusted HR, 0.76; 95% confidence interval (CI), 0.65-0.89], and the association was stronger with increasing total metformin dose [quartile (Q) 1: HR, 0.90; 95% CI, 0.72-1.12; Q2: HR, 0.89; 95% CI, 0.70-1.12; Q3: HR, 0.80; 95% CI, 0.63-1.01; Q4: HR, 0.50; 95% CI, 0.42-0.60, Ptrend < 0.001]. Findings were unchanged in sensitivity analyses, including evaluating only outcomes during the 3- to 10-year period from baseline. CONCLUSION: Our study suggests a potential benefit of metformin use in lowering the risk of subsequent adenomas after polypectomy in patients with type 2 diabetes. IMPACT: Metformin may lower colorectal cancer risk by reducing the formation of precancerous lesions, reinforcing the potential additional benefits of its use. PMID- 26377197 TI - A herbivore-induced plant volatile interferes with host plant and mate location in moths through suppression of olfactory signalling pathways. AB - BACKGROUND: Plants under herbivore attack release volatiles that attract natural enemies, and herbivores in turn avoid such plants. Whilst herbivore-induced plant volatile blends appeared to reduce the attractiveness of host plants to herbivores, the volatiles that are key in this process and particularly the way in which deterrence is coded in the olfactory system are largely unknown. Here we demonstrate that herbivore-induced cotton volatiles suppress orientation of the moth Spodoptera littoralis to host plants and mates. RESULTS: We found that (E) 4,8-dimethyl-1,3,7-nonatriene (DMNT), an induced volatile, is key in herbivore deterrence: DMNT suppressed plant odour- and pheromone-induced behaviours. We then dissected the neurophysiological basis of this interaction. DMNT-responding glomeruli were also activated by other plant compounds, suggesting that S. littoralis possesses no segregated olfactory circuit dedicated exclusively to DMNT. Instead, DMNT suppressed responses to the main pheromone component, (Z)-9 (E)-11-tetradecenyl acetate, and primarily to (Z)-3-hexenyl acetate, a host plant attractant. CONCLUSION: Our study shows that olfactory sensory inhibition, which has previously been reported without reference to an animal's ecology, can be at the core of coding of ecologically relevant odours. As DMNT attracts natural enemies and deters herbivores, it may be useful in the development or enhancement of push-pull strategies for sustainable agriculture. PMID- 26377199 TI - The effect of iron-fortified complementary food and intermittent preventive treatment of malaria on anaemia in 12- to 36-month-old children: a cluster randomised controlled trial. AB - BACKGROUND: Iron deficiency (ID) and malaria co-exist in tropical regions and both contribute to high rates of anaemia in young children. It is unclear whether iron fortification combined with intermittent preventive treatment (IPT) of malaria would be an efficacious strategy for reducing anaemia in young children. METHODS: A 9-month cluster-randomised, single-blinded, placebo-controlled intervention trial was carried out in children aged 12-36 months in south-central Cote d'Ivoire, an area of intense and perennial malaria transmission. The study groups were: group 1: normal diet and IPT-placebo (n = 125); group 2: consumption of porridge, an iron-fortified complementary food (CF) with optimised composition providing 2 mg iron as NaFeEDTA and 3.8 mg iron as ferrous fumarate 6 days per week (CF-FeFum) and IPT-placebo (n = 126); group 3: IPT of malaria at 3-month intervals, using sulfadoxine-pyrimethamine and amodiaquine and no dietary intervention (n = 127); group 4: both CF-FeFum and IPT (n = 124); and group 5: consumption of porridge, an iron-fortified CF with the composition currently on the Ivorian market providing 2 mg iron as NaFeEDTA and 3.8 mg iron as ferric pyrophosphate 6 days per week (CF-FePP) and IPT-placebo (n = 127). The primary outcome was haemoglobin (Hb) concentration. Linear and logistic regression mixed effect models were used for the comparison of the five study groups, and a 2 * 2 factorial analysis was used to assess treatment interactions of CF-FeFum and IPT (study groups 1-4). RESULTS: After 9 months, the Hb concentration increased in all groups to a similar extent with no statistically significant difference between groups. In the 2 * 2 factorial analysis after 9 months, no treatment interaction was found on Hb (P = 0.89). The adjusted differences in Hb were 0.24 g/dl (95 % CI -0.10 to 0.59; P = 0.16) in children receiving IPT and -0.08 g/dl (95 % CI -0.42 to 0.26; P = 0.65) in children receiving CF-FeFum. At baseline, anaemia (Hb <11.0 g/dl) was 82.1 %. After 9 months, IPT decreased the odds of anaemia (odds ratio [OR], 0.46 [95 % CI 0.23-0.91]; P = 0.023), whereas iron fortified CF did not (OR, 0.85 [95 % CI 0.43-1.68]; P = 0.68), although ID (plasma ferritin <30 MUg/l) was decreased markedly in children receiving iron fortified CF (OR, 0.19 [95 % CI 0.09-0.40]; P < 0.001). CONCLUSIONS: IPT alone only modestly decreased anaemia, but neither IPT nor iron fortified CF significantly improved Hb concentration after 9 months. Additionally, IPT did not augment the effect of the iron fortified CF. CF fortified with highly bioavailable iron improved iron status but not Hb concentration, despite three monthly IPT of malaria. Thus, further research is necessary to develop effective combination strategies to prevent and treat anaemia in malaria endemic regions. TRIAL REGISTRATION: http://www.clinicaltrials.gov ; identifier NCT01634945; registered on July 3, 2012. PMID- 26377200 TI - The Effect of Obesity on Functional Outcomes and Complications in Total Ankle Arthroplasty. AB - BACKGROUND: The prevalence of obesity in the United States is staggering. Currently, the effect of obesity on third-generation total ankle replacement (TAR) is unknown. METHODS: We prospectively identified a consecutive series of 455 primary TARs operated between May 2007 and September 2013 who had a minimum follow-up of 2 years. We identified 266 patients with a body mass index (BMI) <30 (control), 116 with a BMI between 30 and 35 (Obese I), and 73 with a BMI >35 (Obese II). Clinical outcomes including wound issues, infection rate, complications, and failure rates were compared. Functional outcomes including American Orthopaedic Foot & Ankle Society hindfoot score, Short Form-36 (SF-36), Short Musculoskeletal Function Assessment (SMFA), Foot and Ankle Disability Index (FADI), and Foot and Ankle Outcome Score (FAOS) were compared. Average patient follow-up in the Obese I group was 44.7 +/- 17.3 months, Obese II was 42.7 +/- 16.4 months, and 45.2 +/- 17.4 months in the control group. RESULTS: Age, race, and smoking history in the obese group were not significantly higher than the control group; however, sex was significantly related to BMI. There was no difference in complication, infection, or failure rates between the groups. Preoperatively, the Obese II group had significantly lower SF-36 scores and higher SMFA function, FADI, and FAOS Symptoms scores. For each of the Obese I, Obese II, and control groups, all functional outcome scores 1 year postoperatively and at most recent follow-up were significantly improved. However, at most recent follow-up, Obese II patients had lower FAOS Pain and SF 36 scores and higher FADI and SMFA Functional scores. CONCLUSION: Total ankle arthroplasty in obese patients was a relatively safe procedure. Although obese patients after TAR had lower functional outcome scores compared to their nonobese counterpart, they did experience significant functional and pain improvements at most recent follow-up. LEVEL OF EVIDENCE: Level III, comparative series. PMID- 26377201 TI - Effect of Obesity on Total Ankle Arthroplasty Outcomes. AB - BACKGROUND: The purpose of this study was to evaluate the effect of obesity on intermediate- to long-term implant failure rates and survivorship after total ankle arthroplasty. METHODS: A chart review was performed for all patients who underwent primary total ankle arthroplasty between 2004 and 2009 with a minimum 5 year follow-up. Patients were separated into a reference group with a body mass index less than 30 kg/m2 and an obese group with an index greater than or equal to 30 kg/m2. Minimum 5-year follow-up outcomes were available for 49 patients in the obese group and 48 patients in the nonobese group. Mean follow-up was 8.2 +/- 2.0 years (range, 5.1-11.5 years) in the reference group and 7.7 +/- 2.0 years (range, 5.0-11.9 years) in the obese group (P = .26). RESULTS: Based on multivariable logistic regression, obese patients had a significantly greater probability of implant failure by final follow-up (adjusted odds ratio, 2.8 [95% CI, 1.04-7.53]; P = .04). Cox regression analysis of 5-year implant survivorship showed no significant difference between the 2 groups (adjusted hazard ratio, 1.89 [95% CI, 0.77-4.65]; P = .17). When compared with obese patients with inflammatory or posttraumatic arthritis, obese patients with osteoarthritis demonstrated a significantly decreased 5-year survivorship (adjusted hazard ratio, 3.73 [95% CI, 1.05-10.43]; P = .04). CONCLUSION: This study demonstrated an increased long-term risk of implant failure among obese patients that was not seen in the intermediate term. Furthermore, obese patients with primary osteoarthritis were found to have a significantly decreased 5-year implant survivorship after ankle arthroplasty as compared with obese patients with inflammatory or posttraumatic arthritis and therefore should be counseled appropriately when deciding between arthroplasty and arthrodesis. LEVEL OF EVIDENCE: Level III, retrospective comparative series. PMID- 26377202 TI - Aryl hydrocarbon receptor-microRNA-212/132 axis in human breast cancer suppresses metastasis by targeting SOX4. AB - BACKGROUND: MicroRNAs (miRNAs) are a class of short non-coding RNAs that pave a new avenue for understanding immune responses and cancer progression. Although the miRNAs are involved in breast cancer development, their axis with the transcription factors that show therapeutic potential in breast cancer is largely unknown. Previous studies showed anti-metastatic roles of agonist-activated aryl hydrocarbon receptor (Ahr) in various breast cancer cell lines. Recently, we demonstrated that agonist-activated Ahr induced a highly conserved miRNA cluster, named miR-212/132, in murine cellular immune compartment. Therefore, current study was performed to examine if this miRNA cluster mediates the anti-metastatic properties of Ahr agonists. METHODS: The expression of miR-212/132 cluster and coding genes were examined by real-time PCR, and the protein levels were detected by western blot. The 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and 3,3' diindolylmethane (DIM) were used to activate Ahr in MDA-MB-231 and T47D breast cancer cells. Chromatin immunoprecipitation (ChIP) assay was used to identify the binding site(s) for Ahr on miR-212/132 promoter. For prediction of potentially target gene of the miRNA cluster, bioinformatics analysis was carried out, and to test targeting, luciferase activity was quantified. Besides, biological effects of Ahr-miR-212/132 axis were examined in vitro by cell migration, expansion and invasion, and examined in vivo by orthotopic model of spontaneous metastasis. RESULTS: The miR-212/132 cluster was transcriptionally activated in MDA-MB-231 and T47D cells by TCDD and DIM, and this activation was regulated by Ahr. A reciprocal correlation was identified between Ahr agonists-induced miR-212/132 and the pro-metastatic SRY-related HMG-box4 (SOX4), and a new specific binding sites for miR-212/132 were identified on the untranslated region (3'UTR) of SOX4. Interestingly, miR-212/132 over-expression showed direct anti-migration, anti expansion and anti-invasion properties, and an inhibition of the miRNA cluster mitigated the anti-invasive properties of TCDD and DIM. Further in vivo studies demonstrated that the Ahr-miR-212/132-SOX4 module was induced by Ahr activation. CONCLUSION: Taken together, the findings provide the first evidences of the synergistic anti-metastatic properties of miR-212/132 cluster through suppression of SOX4. Also, current study suggest a new miRNA-based mechanism elucidating the anti-metastatic properties of Ahr agonists, suggesting possibility of using miR 212/132 to control metastasis in breast cancer patients. PMID- 26377203 TI - Distribution and Abundance of Hopanoid Producers in Low-Oxygen Environments of the Eastern Pacific Ocean. AB - Hopanoids are bacterial membrane lipid biomarker molecules that feature prominently in the molecular fossil record. In the modern marine water column, recent reports implicate bacteria inhabiting low-oxygen environments as important sources of hopanoids to marine sediments. However, the preliminary biogeography reported by recent studies and the environmental conditions governing such distributions can only be confirmed when the numerical abundance of these organisms is known with more certainty. In this study, we employ two different approaches to examine the quantitative significance of phylogenetically distinct hopanoid producers in low-oxygen environments. First, we develop a novel quantitative PCR (qPCR) assay for the squalene hopene cyclase (sqhC) gene, targeting a subset of hopanoid producers previously identified to be important in the eastern North Pacific Ocean. The results represent the first quantitative gene abundance data of any kind for hopanoid producers in the marine water column and show that these putative alphaproteobacterial hopanoid producers are rare, comprising at most 0.2 % of the total bacterial community in our samples. Second, a complementary analysis of existing low-oxygen metagenomic datasets further examined the generality of the qPCR observation. We find that the dominant sqhC sequences in these metagenomic datasets are associated with phyla such as Nitrospinae rather than Proteobacteria, consistent with the qPCR finding that alphaproteobacterial hopanoid producers are not very abundant in low-oxygen environments. In fact, positive correlations between sqhC gene abundance and environmental parameters in these samples identify nitrite availability as a potentially important factor in the ecology of hopanoid producers that dominate low-oxygen environments. PMID- 26377204 TI - Diagnostic yield of repeat sampling with immunoassay, real-time PCR, and toxigenic culture for the detection of toxigenic Clostridium difficile in an epidemic and a non-epidemic setting. AB - Current international guidelines lack definite conclusions regarding repeat stool sampling for the detection of toxigenic Clostridium difficile. We assessed the value of repeat sampling and compared the diagnostic yield in an epidemic to a non-epidemic setting. Consecutive fecal samples obtained during two time frames were analyzed using direct stool immunoassay toxin testing (enzyme immunoassay [EIA]), direct stool real-time PCR toxin gene testing, and toxigenic culture. Samples collected within 7 days of the initial sample were considered repeat tests. In the epidemic setting 989 patients were analyzed, and in the non epidemic setting 1,015. In the epidemic setting 204 patients had two or more specimens included for analysis and in the non-epidemic setting 287 patients. In the epidemic setting 136 samples yielded a positive results, either by EIA or toxigenic culture; of these, 108 were positive according to EIA and 123 according to toxigenic culture. In the first test round 98 (90.7%, 95% CI 85.3 to 96.2), 114 (92.7%, 88.1 to 97.3), and 126 (92.6%, 88.3 to 97.0) positives were detected. Subsequent test rounds yielded 10 (9.3%, 3.8 to 14.7), 9 (7.3%, 2.7 to 11.9), and 10 (7.4%, 3.0 to 11.7) extra positives. In the non-epidemic setting EIA, toxigenic culture and PCR detected 33, 66, and 83 positives. The three tests combined 93 detected positives. In the first test round 30 (90.9%, 81.1 to 100.7), 63 (95.5%, 90.4 to 110.5), 76 (91.6%, 85.6 to 97.5), and 87 (93.5%, 88.6 to 98.5) positives were detected. Subsequent test rounds yielded 3 (9.1%, -0.7 to 18.9), 3 (4.5%, -0.5 to 9.6), 7 (8.4%, 2.5 to 14.4), and 6 (6.5%, 1.5 to 11.4) extra positives. In conclusion, repeat testing resulted in 4.5% to 9.3% extra positives. No significant difference between the settings studied could be demonstrated. Repeat sampling and multimodality testing may be chosen in an outbreak situation to detect all cases, effectively controlling nosocomial spread. PMID- 26377205 TI - 1H, 15N and 13C assignment of the amyloidogenic protein medin using fast-pulsing NMR techniques. AB - Thirty-one proteins are known to form extracellular fibrillar amyloid in humans. Molecular information about many of these proteins in their monomeric, intermediate or fibrillar form and how they aggregate and interact to form the insoluble fibrils is sparse. This is because amyloid proteins are notoriously difficult to study in their soluble forms, due to their inherent propensity to aggregate. Using recent developments in fast NMR techniques, band-selective excitation short transient and band-selective optimized flip-angle short transient heteronuclear multiple quantum coherence we have been able to assign a 5 kDa full-length amyloidogenic protein called medin. Medin is the key protein component of the most common form of localised amyloid with a proposed role in aortic aneurysm and dissection. This assignment will now enable the study of the early interactions that could influence initiation and progression of medin aggregation. The chemical shifts have been deposited in the BioMagRes-Bank accession Nos. 25399 and 26576. PMID- 26377206 TI - 1H, 13C and 15N NMR assignments of a calcium-binding protein from Entamoeba histolytica. AB - We report almost complete sequence specific (1)H, (13)C and (15)N NMR assignments of a 150-residue long calmodulin-like calcium-binding protein from Entamoeba histolytica (EhCaBP6), as a prelude to its structural and functional characterization. PMID- 26377207 TI - Tumor necrosis factor receptor 1 (TNFRI) for ventilator-associated pneumonia diagnosis by cytokine multiplex analysis. AB - BACKGROUND: The diagnosis of ventilator-associated pneumonia (VAP) is challenging. An important aspect to improve outcome is early recognition of VAP and the initiation of the appropriate empirical treatment. We hypothesized that biological markers in plasma can rule out VAP at the moment of clinical suspicion and could rule in VAP before the diagnosis can be made clinically. METHODS: In this prospective study, patients with VAP (n = 24, microbiology confirmed) were compared to controls (n = 19) with a similar duration of mechanical ventilation. Blood samples from the day of VAP diagnosis and 1 and 3 days before were analyzed with a multiplex array for markers of inflammation, coagulation, and apoptosis. The best biomarker combination was selected and the diagnostic accuracy was given by the area under the receiver operating characteristic curve (ROC-AUC). RESULTS: TNF-receptor 1 (TNFRI) and granulocyte colony-stimulating factor (GCSF) were selected as optimal biomarkers at the day of VAP diagnosis, which resulted in a ROC-AUC of 0.96, with excellent sensitivity. Three days before the diagnosis TNFRI and plasminogen activator inhibitor-1 (PAI-1) levels in plasma predicted VAP with a ROC-AUC of 0.79. The slope of IL-10 and PAI-1 resulted in a ROC-AUC of 0.77. These biomarkers improved the classification of the clinical pulmonary infection score when combined. CONCLUSIONS: Concentration of TNFRI and PAI-1 and the slope of PAI-1 and IL-10 may be used to predict the development of VAP as early as 3 days before the diagnosis made clinically. TNFRI and GCSF may be used to exclude VAP at the moment of clinical suspicion. Especially TNFRI seems to be a promising marker for the prediction and diagnosis of VAP. PMID- 26377208 TI - Physiological plasticity of metabolic rates in the invasive honey bee and an endemic Australian bee species. AB - Seasonal variation in metabolic rate and evaporative water loss as a function of ambient temperature were compared in two species of bees. The endemic blue-banded bee, Amegilla chlorocyanea, is a solitary species that is an important pollinator in the south-west Australian biodiversity hotspot. Responses were compared with the European honeybee, Apis mellifera, naturalised in Western Australia almost 200 years ago. Metabolic rate increased exponentially with temperature to a peak in both species, and then declined rapidly, with unique scaling exponents and peaks for all species-by-season comparisons. Early in the austral summer, Apis was less thermally tolerant than Amegilla, but the positions reversed later in the foraging season. There were also significant exponential increases in evaporative water loss with increasing temperature, and both season and species contributed to significantly different responses. Apis maintained relatively consistent thermal performance of metabolic rate between seasons, but at the expense of increased rates of evaporative water loss later in summer. In contrast, Amegilla had dramatically increased metabolic requirements later in summer, but maintained consistent thermal performance of evaporative water loss. Although both species acclimated to higher thermal tolerance, the physiological strategies underpinning the acclimation differed. These findings may have important implications for understanding the responses of these and other pollinators to changing environments and for their conservation management. PMID- 26377209 TI - Clinical Effectiveness of Family Therapeutic Interventions Embedded in General Pediatric Primary Care Settings for Parental Mental Health: A Systematic Review and Meta-analysis. AB - The aim of this systematic review and meta-analysis was to synthesize the available evidence on embedded family therapy interventions in pediatrics and impacts on parental mental health and family functioning outcomes. The Cochrane Collaboration guidelines for systematic reviews and meta-analysis were used for this study. Six electronic databases were searched for randomized controlled trials and cluster randomized trials. The Cochrane Collaboration's Risk of Bias Tool and GRADE system were used to rate the quality of evidence of the included studies. The primary outcomes included parental distress, parental depressive symptoms, and dysfunctional parent-child interaction. Fixed effects models showed statistically significant reductions in parental distress at 6-month and 12-month post-intervention in favor of the intervention group. Family therapy model, intervention level, delivery modality, and dosage moderated intervention impacts on parental distress. Fixed effects models showed statistically significant reductions in parental depressive symptoms and in dysfunctional parent-child interaction in favor of the intervention group. Family therapy interventions can be successfully embedded in general pediatric primary care, and intended outcomes are achieved in this setting. Recommendations for future research and implications for policy development are discussed. PMID- 26377210 TI - Liberating the data from clinical trials. PMID- 26377211 TI - Different Technical Applications of Carbon Nanotubes. AB - Carbon nanotubes have been of great interest because of their simplicity and ease of synthesis. The novel properties of nanostructured carbon nanotubes such as high surface area, good stiffness, and resilience have been explored in many engineering applications. Research on carbon nanotubes have shown the application in the field of energy storage, hydrogen storage, electrochemical supercapacitor, field-emitting devices, transistors, nanoprobes and sensors, composite material, templates, etc. For commercial applications, large quantities and high purity of carbon nanotubes are needed. Different types of carbon nanotubes can be synthesized in various ways. The most common techniques currently practiced are arc discharge, laser ablation, and chemical vapor deposition and flame synthesis. The purification of CNTs is carried out using various techniques mainly oxidation, acid treatment, annealing, sonication, filtering chemical functionalization, etc. However, high-purity purification techniques still have to be developed. Real applications are still under development. This paper addresses the current research on the challenges that are associated with synthesis methods, purification methods, and dispersion and toxicity of CNTs within the scope of different engineering applications, energy, and environmental impact. PMID- 26377212 TI - Study on adsorption and desorption of ammonia on graphene. AB - The gas sensor based on pristine graphene with conductance type was studied theoretically and experimentally. The time response of conductance measurements showed a quickly and largely increased conductivity when the sensor was exposed to ammonia gas produced by a bubble system of ammonia water. However, the desorption process in vacuum took more than 1 h which indicated that there was a larger number of transferred carriers and a strong adsorption force between ammonia and graphene. The desorption time could be greatly shortened down to about 2 min by adding the flow of water-vapor-enriched air at the beginning of the recovery stage which had been confirmed as a rapid and high-efficiency desorption process. Moreover, the optimum geometries, adsorption energies, and the charge transfer number of the composite systems were studied with first principle calculations. However, the theoretical results showed that the adsorption energy between NH3 and graphene was too small to fit for the experimental phenomenon, and there were few charges transferred between graphene and NH3 molecules, which was completely different from the experiment measurement. The adsorption energy between NH4 and graphene increased stage by stage which showed NH4 was a strong donor. The calculation suggested that H2O molecule could help a quick desorption of NH4 from graphene by converting NH4 to NH3 or (NH3)n(H2O)m groups, which was consistent with the experimental results. This study demonstrates that the ammonia gas produced by a bubble system of ammonia water is mainly ammonium groups of NH3 and NH4, and the NH4 moleculars are ideal candidates for the molecular doping of graphene while the interaction between graphene and the NH3 moleculars is weak. PMID- 26377213 TI - Microwave-Assisted Synthesis of Carbon-Based (N, Fe)-Codoped TiO2 for the Photocatalytic Degradation of Formaldehyde. AB - A microwave-assisted sol-gel method was used to synthesize (N, Fe)-codoped activated carbon (AC)/TiO2 photocatalyst for enhanced optical absorption in the visible light region. The prepared samples were characterized via X-ray diffraction, scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, Brunauer-Emmett-Teller analysis, ultraviolet-visible light spectroscopy, X-ray photoelectron spectroscopy, and photoluminescence spectroscopy. The results showed no significant difference in the surface area of AC/TiO2 (approximately 500 m(2)/g) after doping. TiO2 was uniformly distributed on the surface of AC, which exhibited coexisting anatase and rutile structures with a mean crystallite diameter of approximately 20 nm. N and Fe monodoping on AC/TiO2 reduced the energy band gap of TiO2 to 2.81 and 2.79 eV, respectively, which mainly attributed to the impurity energy formed in the energy gap of TiO2. In (N, Fe)-codoped AC/TiO2, N and Fe are incorporated into the TiO2 framework and narrow the band gap of TiO2 to 2.58 eV, thereby causing a large redshift. Codoping of N and Fe enhanced the production of hydroxyl radicals (?OH) and improved the photocatalytic activity of the resultant AC/TiO2 compared with those of undoped and N- or Fe-monodoped AC/TiO2. N-Fe-AC/TiO2 degraded 93 % of the formaldehyde under Xe-lamp irradiation. Moreover, the photocatalyst was easily recyclable. In summary, a novel and efficient method to mineralize low concentrations of HCHO in wastewater was discovered. PMID- 26377214 TI - Comparative study of photocatalytic activities of hydrothermally grown ZnO nanorod on Si(001) wafer and FTO glass substrates. AB - ZnO nanorods have been grown on Si(001) wafer and fluorine-doped tin oxide (FTO) glass substrates for 1 and 4 h with the hydrothermal methods. The morphologies and photocatalytic activities of the ZnO nanorods were found to depend on the substrates. We investigated their properties by using spectroscopic analysis and demonstrated that the shape of nanorod and the ratios of external defects can be controlled by varying the substrates. Our experiments revealed that the nanorods grown on Si(001) have a single-crystalline wurtzite structure with (002) facets and that the number of surface oxygen defects increases with their length as the growth time increases. The nanorods grown on Si(001) have different facets, in particular wider (002) facets, and a higher ratio of the oxygen defect than the nanorods on FTO glass substrate. Moreover, the photocatalytic activities with respect to 2-aminothiophenol (2-ATP) of these nanorods were investigated with high-resolution photoemission spectroscopy (HRPES). We demonstrated that their photocatalytic activity is influenced by the ratios of surface oxygen defects, which varies with the substrate surface. PMID- 26377215 TI - Inkjet Printing of Colloidal Nanospheres: Engineering the Evaporation-Driven Self Assembly Process to Form Defined Layer Morphologies. AB - We report on inkjet printing of aqueous colloidal suspensions containing monodisperse silica and/or polystyrene nanosphere particles and a systematic study of the morphology of the deposits as a function of different parameters during inkjet printing and solvent evaporation. The colloidal suspensions act as a model ink for an understanding of layer formation processes and resulting morphologies in inkjet printing in general. We investigated the influence of the surface energy and the temperature of the substrate, the formulation of the suspensions, and the multi-pass printing aiming for layer stacks on the morphology of the deposits. We explain our findings with models of evaporation driven self-assembly of the nanosphere particles in a liquid droplet and derive methods to direct the self-assembly processes into distinct one- and two dimensional deposit morphologies. PMID- 26377216 TI - Ameliorative Influence of Green Tea Extract on Copper Nanoparticle-Induced Hepatotoxicity in Rats. AB - The potential toxicity of copper nanoparticles (CNPs) to the human health and environment remains a critical issue. In the present study, we investigated the protective influence of an aqueous extract of green tea leaves (GTE) against CNPs induced (20-30 nm) hepatotoxicity. Four different groups of rats were used: group I was the control, group II received CNPs (40 mg/kg BW), group III received CNPs plus GTE, and group IV received GTE alone. We highlighted the hepatoprotective effect of GTE against CNPs toxicity through monitoring the alteration of liver enzyme activity, antioxidant defense mechanism, histopathological alterations, and DNA damage evaluation. The rats that were given CNPs only had a highly significant elevation in liver enzymes, alteration in oxidant-antioxidant balance, and severe pathological changes. In addition, we detected a significant elevation of DNA fragmentation percentage, marked DNA laddering, and significance over expression of both caspase-3 and Bax proteins. The findings for group III clarify the efficacy of GTE as a hepatoprotectant on CNPs through improving the liver enzyme activity, antioxidant status, as well as suppressing DNA fragmentation and the expression of the caspase-3 and Bax proteins. In conclusion, GTE was proved to be a potential hepatoprotective additive as it significantly ameliorates the hepatotoxicity and apoptosis induced by CNPs. PMID- 26377217 TI - Hydrothermal Synthesis and Photocatalytic Property of beta-Ga2O3 Nanorods. AB - Gallium oxide (Ga2O3) nanorods were facilely prepared by a simple hydrothermal synthesis, and their morphology and photocatalytic property were studied. The gallium oxide hydroxide (GaOOH) nanorods were formed in aqueous growth solution containing gallium nitrate and ammonium hydroxide at 95 degrees C of growth temperature. Through the calcination treatment at 500 and 1000 degrees C for 3 h, the GaOOH nanorods were converted into single crystalline alpha-Ga2O3 and beta Ga2O3 phases. From X-ray diffraction analysis, it could be confirmed that a high crystalline quality of beta-Ga2O3 nanorods was achieved by calcinating at 1000 degrees C. The thermal behavior of the Ga2O3 nanorods was also investigated by differential thermal analysis, and their vibrational bands were identified by Fourier transform infrared spectroscopy. In order to examine the photocatalytic activity of samples, the photodegradation of Rhodamine B solution was observed under UV light irradiation. As a result, the alpha-Ga2O3 and beta-Ga2O3 nanorods exhibited high photodegeneration efficiencies of 62 and 79 %, respectively, for 180 min of UV irradiation time. PMID- 26377218 TI - Characterization of Au and Bimetallic PtAu Nanoparticles on PDDA-Graphene Sheets as Electrocatalysts for Formic Acid Oxidation. AB - Nanocomposite materials of the Au nanoparticles (Au/PDDA-G) and the bimetallic PtAu nanoparticles on poly-(diallyldimethylammonium chloride) (PDDA)-modified graphene sheets (PtAu/PDDA-G) were prepared with hydrothermal method at 90 degrees C for 24 h. The composite materials Au/PDDA-G and PtAu/PDDA-G were evaluated by transmission electron microscopy (TEM), X-ray diffraction (XRD), X ray photoelectron spectroscopy (XPS), and thermogravimetric analysis (TGA) for exploring the structural characterization for the electrochemical catalysis. According to TEM results, the diameter of Au and bimetallic PtAu nanoparticles is about 20-50 and 5-10 nm, respectively. X-ray diffraction (XRD) results indicate that both of PtAu and Au nanoparticles exhibit the crystalline plane of (111), (200), (210), and (311). Furthermore, XRD data also show the 2 degrees -3 degrees difference between pristine graphene sheets and the PDDA-modified graphene sheets. For the catalytic activity tests of Au/PDDA-G and PtAu/PDDA-G, the mixture of 0.5 M aqueous H2SO4 and 0.5 M aqueous formic acid was used as model to evaluate the electrochemical characterizations. The catalytic activities of the novel bimetallic PtAu/graphene electrocatalyst would be anticipated to be superior to the previous electrocatalyst of the cubic Pt/graphene. PMID- 26377222 TI - Sperm postacrosomal WW domain-binding protein is not required for mouse egg activation. AB - To begin embryonic development, the zygote must resume the cell cycle correctly after stimulation by sperm-borne oocyte-activating factors (SOAFs). The postacrosomal WW domain-binding protein (PAWP) is one of the strongest SOAF candidates and is widely conserved among eutherian mammals. It has been reported that the microinjection of recombinant PAWP protein can trigger not only Ca(2+) oscillations in mammalian eggs but also intracellular Ca(2+) release in amphibian eggs. It was also suggested that PAWP is involved in the formation of high quality spermatozoa. On the other hand, negligible SOAF activity for PAWP cRNA has also been reported. In this study, we generated PAWP null mice and examined the fertilizing ability of male mice. Electron microscopy showed no aberrant morphology in spermatogenesis. Intracytoplasmic injection of a single spermatozoon from the null mouse line showed that depletion of PAWP elicited no quantitative differences in Ca(2+) oscillations or in subsequent development of the embryos. We conclude that PAWP does not play an essential role in mouse fertilization. PMID- 26377220 TI - Limited genomic divergence between intraspecific forms of Culex pipiens under different ecological pressures. AB - BACKGROUND: Divergent selection can be a major driver of ecological speciation. In insects of medical importance, understanding the speciation process is both of academic interest and public health importance. In the West Nile virus vector Culex pipiens, intraspecific pipiens and molestus forms vary in ecological and physiological traits. Populations of each form appear to share recent common ancestry but patterns of genetic differentiation across the genome remain unknown. Here, we undertook an AFLP genome scan on samples collected from both sympatric and allopatric populations from Europe and the USA to quantify the extent of genomic differentiation between the two forms. RESULTS: The forms were clearly differentiated but each exhibited major population sub-structuring between continents. Divergence between pipiens and molestus forms from USA was higher than in both inter- and intra-continental comparisons with European samples. The proportion of outlier loci between pipiens and molestus (~3 %) was low but consistent in both continents, and similar to those observed between sibling species of other mosquito species which exhibit contemporary gene flow. Only two of the outlier loci were shared between inter-form comparisons made within Europe and USA. CONCLUSION: This study supports the molestus and pipiens status as distinct evolutionary entities with low genomic divergence. The low number of shared divergent loci between continents suggests a relatively limited number of genomic regions determining key typological traits likely to be driving incipient speciation and/or adaptation of molestus to anthropogenic habitats. PMID- 26377219 TI - Molecular aspects of zygotic embryogenesis in sunflower (Helianthus annuus L.): correlation of positive histone marks with HaWUS expression and putative link HaWUS/HaL1L. AB - MAIN CONCLUSION: The link HaWUS/ HaL1L , the opposite transcriptional behavior, and the decrease/increase in positive histone marks bond to both genes suggest an inhibitory effect of WUS on HaL1L in sunflower zygotic embryos. In Arabidopsis, a group of transcription factors implicated in the earliest events of embryogenesis is the WUSCHEL-RELATED HOMEOBOX (WOX) protein family including WUSCHEL (WUS) and other 14 WOX protein, some of which contain a conserved WUS-box domain in addition to the homeodomain. WUS transcripts appear very early in embryogenesis, at the 16-cell embryo stage, but gradually become restricted to the center of the developing shoot apical meristem (SAM) primordium and continues to be expressed in cells of the niche/organizing center of SAM and floral meristems to maintain stem cell population. Moreover, WUS has decisive roles in the embryonic program presumably promoting the vegetative-to-embryonic transition and/or maintaining the identity of the embryonic stem cells. However, data on the direct interaction between WUS and key genes for seed development (as LEC1 and L1L) are not collected. The novelty of this report consists in the characterization of Helianthus annuus WUS (HaWUS) gene and in its analysis regarding the pattern of the methylated lysine 4 (K4) of the Histone H3 and of the acetylated histone H3 during the zygotic embryo development. Also, a parallel investigation was performed for HaL1L gene since two copies of the WUS-binding site (WUSATA), previously identified on HaL1L nucleotide sequence, were able to be bound by the HaWUS recombinant protein suggesting a not described effect of HaWUS on HaL1L transcription. PMID- 26377223 TI - MicroRNA-212 Regulates the Expression of Olfactomedin 1 and C-Terminal Binding Protein 1 in Human Endometrial Epithelial Cells to Enhance Spheroid Attachment In Vitro. AB - Successful embryo implantation requires a synchronized dialogue between a competent blastocyst and the receptive endometrium, which occurs in a limited time period known as the "window of implantation." Recent studies suggested that down-regulation of olfactomedin 1 (OLFM1) in the endometrium and fallopian tube is associated with receptive endometrium and tubal ectopic pregnancy in humans. Interestingly, the human chorionic gonadotropin (hCG) induces miR-212 expression, which modulates OLFM1 and C-terminal binding protein 1 (CTBP1) expressions in mouse granulosa cells. Therefore, we hypothesized that embryo-derived hCG would increase miR-212 expression and down-regulate OLFM1 and CTBP1 expressions to favor embryo attachment onto the female reproductive tract. We found that hCG stimulated the expression of miR-212 and down-regulated OLFM1 but not CTBP1 mRNA in both human endometrial (Ishikawa) and fallopian (OE-E6/E7) epithelial cells. However, hCG suppressed the expression of OLFM1 and CTBP1 proteins in both cell lines. The 3'UTR of both OLFM1 and CTBP1 contained binding sites for miR-212. The miR-212 precursor suppressed luciferase expression, whereas the miR-212 inhibitor stimulated luciferase expression of the wild-type (WT)-OLFM1 and WT-CTBP1 reporter constructs. Furthermore, hCG (25 IU/ml) treatments stimulated trophoblastic (Jeg-3) spheroid (blastocyst surrogate) attachment onto Ishikawa and OE-E6/E7 cells. Transfection of miR-212 precursor increased Jeg-3 spheroid attachment onto Ishikawa cells and decreased OLFM1 and CTBP1 protein expressions, whereas the opposite occurred with miR-212 inhibitor. Taken together, hCG stimulated miR-212, which in turn down-regulated OLFM1 and CTBP1 expression in fallopian and endometrial epithelial cells to favor spheroid attachment. PMID- 26377224 TI - Innovative solution for portable suction machine. PMID- 26377221 TI - Cigarette smoke exposure triggers the autophagic cascade via activation of the AMPK pathway in mice. AB - We previously demonstrated that cigarette smoke (CS) exposure decreases primordial follicle counts and induces autophagy in ovarian granulosa cells in preference to apoptosis. Therefore, the objective of this study was to investigate molecular targets underlying smoke-induced activation of the reparative autophagy pathway in the ovary. Briefly, ovarian homogenates were prepared from adult female mice exposed to mainstream CS twice daily for 8 wk, using a whole-body exposure system. A gene array revealed that CS exposure induced a greater than 2-fold significant increase in the expression of proautophagic genes Cdkn1b, Map1lc3a, Bad, and Sqstm1/p62. A significant increase in Prkaa2, Pik3c3, and Maplc31b expression, as well as a significant decrease in Akt1 and Mtor expression, was detected by quantitative PCR. The 5'-AMP-activated protein kinase catalytic subunit (AMPK) alpha1 + alpha2 and ATG7 protein expression was significantly increased, whereas AKT1, mTOR, CDKN1B/p27, and CXCR4 proteins were significantly decreased in CS exposed versus control ovaries. Up regulation of AMPK alpha1 + alpha2, a known initiator of autophagic signaling, and ATG7 further suggests activation of the autophagy cascade. Two prosurvival factors, AKT and mTOR, were decreased in expression, an outcome that favors induction of the autophagy pathway, whereas decreased levels of CDKN1B is suggestive of cell cycle dysregulation. In summary, our data suggest that CS exposure induces ovarian follicle loss through induction of the autophagic cascade via the AMPK pathway together with inhibition of antiautophagic markers AKT and mTOR. We further postulate that toxicant-induced dysregulation of reparative autophagy is a novel pathway central to impaired follicle development and subfertility. PMID- 26377225 TI - Positive correlation of plasma PCSK9 levels with HbA1c in patients with type 2 diabetes. AB - BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) has been demonstrated to be involved in not only lipid metabolism but also glucose homeostasis. Glycated haemoglobin (HbA1c ) is a 'gold standard' for monitoring long-term glycaemic control. However, the correlation of plasma PCSK9 levels with HbA1c remains undetermined. METHODS: We consecutively enrolled 805 subjects undergoing coronary angiography, including 176 patients with type 2 diabetes mellitus (T2DM) and 629 non-diabetic patients. The baseline characteristics were collected, and serum PCSK9 level was assessed by ELISA. Univariable regression analysis and multiple-variable regression analysis were used to examine the associations of PCSK9 with HbA1c . Furthermore, the HbA1c was compared across the tertiles of PCSK9 levels. And also, PCSK9 levels were compared in poorly controlled (HbA1c >= 7.0%) and well-controlled (HbA1c < 7.0%) patients with T2DM. RESULTS: PCSK9 levels were positively correlated with low-density lipoprotein cholesterol in both T2DM and non-T2DM. Univariable regression analysis revealed a positive association between PCSK9 and HbA1c in patients with T2DM (beta = 0.255, p = 0.001) but not in patients without diabetes (beta = 0.061, p = 0.128). Multiple-variable regression analysis exhibited that PCSK9 was independently correlated with HbA1c in T2DM after adjustment for traditional atherosclerotic risk factors (beta = 0.197, p = 0.020). Moreover, HbA1c level was higher in patients with the highest tertile of PCSK9 than that in the lowest tertile (p = 0.042). Additionally, higher levels of PCSK9 were found in poorly controlled group compared with the well-controlled group (p = 0.029). CONCLUSIONS: Data suggest a positive correlation of PCSK9 levels with HbA1c in patients with T2DM but not in patients without T2DM, indicating a potential role of PCSK9 in T2DM. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26377226 TI - Synthesis and Postpolymerization Modification of One-Pot omega-Pentadecalactone Block-like Copolymers. AB - We report the one-pot copolymerization of omega-pentadecalactone (PDL) to produce tri- and diblock-like copolymers with the ability to undergo postpolymerization modification. The epsilon-substituted epsilon-lactone (epsilonSL), menthide (MI), was copolymerized with PDL to introduce side chain functionality into poly(omega pentadecalactone) (PPDL) copolymers. The copolymerization was followed by quantitative 13C NMR spectroscopy, which revealed that the polymerization of MI occurred before the incorporation of PDL into the polymer chain to form a block like copolymer. Transesterification side reactions were not found to occur interblock, although intrablock transesterification side reactions occurred only within the PPDL section. The same effect was demonstrated across a range of relative molar equivalents of monomers, and the generality of the approach was further demonstrated with the copolymerization of PDL with other epsilonSL monomers. Finally, the copolymerization of PDL with an alkene-functionalized epsilonSL was shown to produce one-pot PDL block-like copolymers that could undergo postpolymerization modification by thiol-ene addition to produce block copolymers with a range of characteristics in a simple procedure. PMID- 26377227 TI - Insulin resistance in heart failure: widening the divide between reduced and preserved ejection fraction? PMID- 26377228 TI - The Second World Cholera Pandemic (1826-1849) in the Kingdom of the Two Sicilies with Special Reference to the Towns of San Prisco and Forio d'Ischia. AB - The second world cholera pandemic in Europe (1829-1849) was significant because of its geographic extent and the enormous numbers of people who fell ill or died. It was also singularly important because it demonstrated the profound levels of ignorance in both Europe and North America concerning the cause, modes of transmission, and treatment of cholera. This paper discusses the pandemic in the Kingdom of the Two Sicilies in great detail. Even though medical and public health authorities in this kingdom had several years to prepare for cholera's eventual arrival in 1836-1837, their elaborate preventive and therapeutic measures proved no more successful than elsewhere. Despite their efforts, it was estimated that there were 32,145 cases of cholera in the city of Naples by July 1837. Some 19,470 people were estimated to have died among the city's then 357,283 population. This amounted to a cholera-specific mortality rate of 54.5/1000 population. Sicily was also severely affected by the epidemic. It was estimated that 69,000 people died of cholera in Sicily, 24,000 of them in the city of Palermo. Two rural towns in the kingdom, San Prisco and Forio d'Ischia, were selected for in-depth epidemiologic study. The former had a population of 3700 in 1836-1837, while the latter had a population of 5500. The economic basis of both towns was agriculture. However, because Forio is located on an island, fishing and sea transport were then also important industries. Cholera appeared in San Prisco in July 1837 and quickly swept through the population. By August, the epidemic was essentially over. It is estimated that some 109 people died from cholera in San Prisco for a disease-specific mortality rate of 29.5/1000 population. The age range of those who died from cholera was 1 to 90 years. The majority of deaths (60.6 %) were among women. The first cases of cholera appeared in Forio d'Ischia in June 1837. The epidemic then peaked in July. It is estimated that approximately 316 people died from cholera in Forio out of a population of 5500. This resulted in a cholera-specific mortality rate of 57.5/1000 population. Among the first 42 fatal cases in whom the disease was documented on their death certificates, ages ranged from 15 to 88 years. The mean age was 52.4 years. The majority of deaths (57.1 %) were among women. We reached beyond the statistics of this epidemic by presenting an in-depth study of the first person to die from cholera in Forio d'Ischia, Nicola Antonio Insante. By focusing on him, we were able to develop a broad account of the social and economic consequences of his death on his family. At the same time, our research demonstrated the resiliency of his immediate and distant descendants. Similarly, we discuss the D'Ambra and Scola families of Forio d'Ischia, and the Caruso and Valenziano families of San Prisco, among whom a number died from cholera in 1837. PMID- 26377230 TI - Validity and Reliability of the Spanish Version of the Revised Self-Monitoring Scale. AB - Self-Monitoring (SM) is a concept that refers to individual differences in this orientation toward regulation of social behavior. The goal of the present research was to provide a Spanish adaptation of Snyder and Gangestad's (1986) Revised SM Scale. After conducting an initial pilot study, results showed that the Spanish version of the scale had good internal reliability and adequate factor structure. In Study 1, analyses support a unidimensional structure of the scale (chi2/df = 2.64; GFI = .97; IFI = .97; TLI = .96; RMSEA = .06). In Study 2, the scale showed discriminant validity from other individual differences measures, such as Need for Cognition (r = 0.12 p = 0.14), Social Desirability (r = 0.06, p > .45) and Extraversion (r = 0.28 p = .001). In Study 3, the scale showed adequate test-retest reliability (r = 0.71, p < .001). Finally, using a paradigm of attitude-behavior consistenty, Study 4 showed that the validated scale also had good predictive validity (B = -0.819, p = .035). PMID- 26377229 TI - Sleep spindles and human cortical nociception: a surface and intracerebral electrophysiological study. AB - KEY POINTS: Sleep spindle are usually considered to play a major role in inhibiting sensory inputs. Using nociceptive stimuli in humans, we tested the effect of spindles on behavioural, autonomic and cortical responses in two experiments using surface and intracerebral electroencephalographic recordings. We found that sleep spindles do not prevent arousal reactions to nociceptive stimuli and that autonomic reactivity to nociceptive inputs is not modulated by spindle activity. Moreover, neither the surface sensory, nor the insular evoked responses were modulated by the spindle, as detected at the surface or within the thalamus. The present study comprises the first investigation of the effect of spindles on nociceptive information processing and the results obtained challenge the classical inhibitory effect of spindles. ABSTRACT: Responsiveness to environmental stimuli declines during sleep, and sleep spindles are often considered to play a major role in inhibiting sensory inputs. In the present study, we tested the effect of spindles on behavioural, autonomic and cortical responses to pain, in two experiments assessing surface and intracerebral responses to thermo-nociceptive laser stimuli during the all-night N2 sleep stage. The percentage of arousals remained unchanged as a result of the presence of spindles. Neither cortical nociceptive responses, nor autonomic cardiovascular reactivity were depressed when elicited within a spindle. These results could be replicated in human intracerebral recordings, where sleep spindle activity in the posterior thalamus failed to depress the thalamocortical nociceptive transmission, as measured by sensory responses within the posterior insula. Hence, the assumed inhibitory effect of spindles on sensory inputs may not apply to the nociceptive system, possibly as a result of the specificity of spinothalamic pathways and the crucial role of nociceptive information for homeostasis. Intriguingly, a late scalp response commonly considered to reflect high-order stimulus processing (the 'P3' potential) was significantly enhanced during spindling, suggesting a possible spindle-driven facilitation, rather than attenuation, of cortical nociception. PMID- 26377231 TI - Ultrathin efficient perovskite solar cells employing a periodic structure of a composite hole conductor for elevated plasmonic light harvesting and hole collection. AB - We developed a molecule/polymer composite hole transporting material (HTM) with a periodic microstructure for morphology replication of a corrugated Au electrode, which in combination plays a dual role in the optical and electronic enhancement of high performance perovskite solar cells (PSCs). The electro-optics revealed that perovskite couldn't readily extinct the red light even though the thickness increased to 370 nm, but we found that the quasi periodic microstructure composite (PMC) HTM in combination with the conformal Au electrode could promote the absorption through the enhanced cavity effects, leading to comparable absorption even using much thinner perovskite (240 nm). We identified that the cavity was the combination of Fabry-Perot interferometer and surface plasmonic resonance, with light harvesting enhancement through surface plasmon polariton or waveguide modes that propagate in the plane of the perovskite layer. On the other hand, the PMC HTM increased hole conductivity by one order of magnitude with respect to standard spiro-OMeTAD HTM due to molecular packing and self-assembly, embodying traceable hole mobility and density elevation up to 3 times, and thus the hysteresis was greatly avoided. Owing to dual optical and electronic enhancement, the PMC PSC afforded high efficiency PSC using as thin as 240 nm perovskite layer, delivering a V(oc) of 1.05 V, J(sc) of 22.9 mA cm(-2), FF of 0.736, and efficiency amounting to 17.7% PCE, the highest efficiency with ultrathin perovskite layer. PMID- 26377233 TI - Outpatient Combined Group and Individual Cognitive-Behavioral Treatment for Patients With Migraine and Tension-Type Headache in a Routine Clinical Setting. AB - OBJECTIVE: To test the long-term clinical effectiveness (follow-up at 3, 6 and 12 months) of an outpatient combined group and individual cognitive-behavioral treatment (CBT) for headache patients following standard medical care. A decrease in headache intensity, frequency, headache-specific impairment, depression, and change of pain-related cognitions was expected. BACKGROUND: The efficacy of CBT for primary headaches has been confirmed in research, yet the translation into clinical practice has remained untested thus far. DESIGN: In this single-group outcome study, 87 headache patients diagnosed with migraine and/or tension-type headache received (1) headache-specific medication for 10 weeks and (2) a subsequent CBT treatment made up of 13 individual and 12 group sessions consisting of psychoeducation, progressive muscle relaxation, coping strategies for pain and stress, and goal setting skills. Booster group sessions after 3 and 6 months were implemented to stimulate individual goal attainment, and follow-up measures were recorded up to 12 months. RESULTS: A significant decrease was found for all primary and secondary outcome criteria, ie, average headache intensity (prae M: 6.0, standard deviation [SD]: 1.5 vs follow-up [FU] 1 year M: 5.1, SD: 1.9), headache frequency (prae M: 16.0, SD: 9.5 vs FU 1 year M: 13.4, SD: 9.9), and catastrophizing (prae M: 3.4, SD: 1.0 vs FU 1 year M: 2.6, SD: 1.1). Coping strategies were increased (prae M: 3.4, SD: .9 vs FU 1 year M: 4.0, SD: 1.0). CONCLUSION: CBT treatment is a useful component within a routine clinical setting and can improve standard medical care thereby helping patients in managing their headache pain. PMID- 26377234 TI - Further New Xenicanes from a Chinese Collection of the Brown Alga Dictyota plectens. AB - Four new xenicanes, namely 4alpha-hydroxyisodictyohemiacetal (1), 4alpha hydroxyisodictyoacetal (2), 13,18-diacetoxy-4-hydroxyisodictyo-19-al (3), and 4alpha-hydroxypachylactone (8), were isolated from a Chinese collection of the brown alga Dictyota plectens, along with four known analogues (4-7). The structures of the new diterpenes were determined by extensive spectroscopic data analysis. All compounds were evaluated for their antiviral activities against human immunodeficiency virus type 1 (HIV-1) and the highly pathogenic avian influenza A (H5N1) virus, and inhibitory effects on lipopolysaccharide (LPS) induced nitric oxide (NO) production in mouse peritoneal macrophages (PEMPhi). PMID- 26377232 TI - Inhibition of Gli/hedgehog signaling in prostate cancer cells by "cancer bush" Sutherlandia frutescens extract. AB - Sutherlandia frutescens is a medicinal plant, traditionally used to treat various types of human diseases, including cancer. Previous studies of several botanicals link suppression of prostate cancer growth with inhibition of the Gli/hedgehog (Gli/Hh) signaling pathway. Here we hypothesized the anti-cancer effect of S. frutescens was linked to its inhibition of the Gli/Hh signaling in prostate cancer. We found a dose- and time-dependent growth inhibition in human prostate cancer cells, PC3 and LNCaP, and mouse prostate cancer cell, TRAMP-C2, treated with S. frutescens methanol extract (SLE). We also observed a dose-dependent inhibition of the Gli-reporter activity in Shh Light II and TRAMP-C2QGli cells treated with SLE. In addition, SLE can inhibit Gli/Hh signaling by blocking Gli1 and Ptched1 gene expression in the presence of a Gli/Hh signaling agonist (SAG). A diet supplemented with S. frutescens suppressed the formation of poorly differentiated carcinoma in prostates of TRAMP mice. Finally, we found Sutherlandioside D was the most potent compound in the crude extract that could suppress Gli-reporter in Shh Light II cells. Together, this suggests that the S. frutescens extract may exert anti-cancer effect by targeting Gli/Hh signaling, and Sutherlandioside D is one of the active compounds. PMID- 26377236 TI - A case of mixed connective tissue disease with pseudo-pseudo Meigs' syndrome (PPMS)-like features. AB - Pseudo-pseudo Meigs' syndrome (PPMS) has been reported to be a rare presentation of patients with systemic lupus erythematosus (SLE). However, such a presentation is not common in other forms of connective tissue disease. We presented a case of gross ascites, pleural effusion, and marked elevation of CA-125 level (PPMS-like features) that led to a diagnosis of MCTD. The patient responded to systemic steroid therapy. PMID- 26377237 TI - Reliable fabrication of plasmonic nanostructures without an adhesion layer using dry lift-off. AB - Lift-off is the most commonly used pattern-transfer method to define lithographic plasmonic metal nanostructures. A typical lift-off process is realized by dissolving patterned resists in solutions, which has the limits of low yield when not using adhesion layers and incompatibility with the fabrication of some specific structures and devices. In this work, we report an alternative 'dry' lift-off process to obtain metallic nanostructures via mechanical stripping by using the advantage of poor adhesion between resists and noble metal films. We show that this dry stripping lift-off method is effective for both positive- and negative-tone resists to fabricate sparse and densely-packed plasmonic nanostructures, respectively. In particular, this method is achieved without using an adhesion layer, which enables the mitigation of plasmon damping to obtain larger field enhancement. Dark-field scattering, one-photon luminescence and surface-enhanced Raman scattering measurements were performed to demonstrate the improved quality factor of the plasmonic nanostructures fabricated by this dry lift-off process. PMID- 26377235 TI - Changing Friend Selection in Middle School: A Social Network Analysis of a Randomized Intervention Study Designed to Prevent Adolescent Problem Behavior. AB - Adolescent friendships that promote problem behavior are often chosen in middle school. The current study examines the unintended impact of a randomized school based intervention on the selection of friends in middle school, as well as on observations of deviant talk with friends 5 years later. Participants included 998 middle school students (526 boys and 472 girls) recruited at the onset of middle school (age 11-12 years) from three public middle schools participating in the Family Check-up model intervention. The current study focuses only on the effects of the SHAPe curriculum-one level of the Family Check-up model-on friendship choices. Participants nominated friends and completed measures of deviant peer affiliation. Approximately half of the sample (n = 500) was randomly assigned to the intervention, and the other half (n = 498) comprised the control group within each school. The results indicate that the SHAPe curriculum affected friend selection within school 1 but not within schools 2 or 3. The effects of friend selection in school 1 translated into reductions in observed deviancy training 5 years later (age 16-17 years). By coupling longitudinal social network analysis with a randomized intervention study, the current findings provide initial evidence that a randomized public middle school intervention can disrupt the formation of deviant peer groups and diminish levels of adolescent deviance 5 years later. PMID- 26377238 TI - Oxaliplatin immuno hybrid nanoparticles for active targeting: an approach for enhanced apoptotic activity and drug delivery to colorectal tumors. AB - Tumor necrosis factor related apoptosis inducing ligand (TRAIL) proved to be a promising new target for colorectal cancer treatment. Elevated expression of TRAIL protein in tumor cells distinguishes it from healthy cells, thereby delivering the drug at the specific site. Here, we formulated oxaliplatin immunohybrid nanoparticles (OIHNPs) to deliver oxaliplatin and anti-TRAIL for colorectal cancer treatment in xenograft tumor models. The polymeric chitosan layer binds to the lipid film with the mixture of phospholipids by an ultra sound method followed by conjugating with thiolated antibody using DSPE-PEG-mal3400, resulting in the formation of OIHNPs. The polymer layer helps in more encapsulation of the drug (71 +/- 0.09%) with appreciable particle size (95 +/- 0.01 nm), and lipid layer prevents degradation of the drug in serum by preventing nanoparticle aggregation. OIHNPs have shown a 4-fold decrease in the IC50 value compared to oxaliplatin in HT-29 cells by the MTT assay. These immuno nanoparticles represent the successful uptake and internalization of oxaliplatin in HT-29 cells rather than in MCF-7 cells determined by triple fluorescence method. Apoptotic activity in vitro of OIHNPs was determined by the change in the mitochondria membrane potential that further elevates its anti-tumor property. Furthermore, the conjugated nanoparticles can effectively deliver the drug to the tumor sites, which can be attributed to its ability in reducing tumor mass and tumor volume in xenograft tumor models in vivo along with sustaining its release in vitro. These findings indicated that the oxaliplatin immuno-hybrid nanoparticles would be a promising nano-sized active targeted formulation for colorectal-tumor targeted therapy. PMID- 26377239 TI - Kagami-Ogata syndrome: a clinically recognizable upd(14)pat and related disorder affecting the chromosome 14q32.2 imprinted region. AB - Human chromosome 14q32.2 carries paternally expressed genes including DLK1 and RTL1, and maternally expressed genes including MEG3 and RTL1as, along with the germline-derived DLK1-MEG3 intergenic differentially methylated region (IG-DMR) and the postfertilization-derived MEG3-DMR. Consistent with this, paternal uniparental disomy 14 (upd(14)pat), and epimutations (hypermethylations) and microdeletions affecting the IG-DMR and/or the MEG3-DMR of maternal origin, result in a unique phenotype associated with characteristic face, a small bell shaped thorax with coat-hanger appearance of the ribs, abdominal wall defects, placentomegaly and polyhydramnios. Recently, the name 'Kagami-Ogata syndrome' (KOS) has been approved for this clinically recognizable disorder. Here, we review the current knowledge about KOS. Important findings include the following: (1) the facial 'gestalt' and the increased coat-hanger angle constitute pathognomonic features from infancy through childhood/puberty; (2) the unmethylated IG-DMR and MEG3-DMR of maternal origin function as the imprinting control centers in the placenta and body respectively, with a hierarchical interaction regulated by the IG-DMR for the methylation pattern of the MEG3-DMR in the body; (3) RTL1 expression level becomes ~2.5 times increased in the absence of functional RTL1as-encoded microRNAs that act as a trans-acting repressor for RTL1; (4) excessive RTL1 expression and absent MEG expression constitute the primary underlying factor for the phenotypic development; and (5) upd(14)pat accounts for approximately two-thirds of KOS patients, and epimutations and microdeletions are identified with a similar frequency. Furthermore, we refer to diagnostic and therapeutic implications. PMID- 26377241 TI - Evaluation of a two-step iterative resampling procedure for internal validation of genome-wide association studies. AB - Genome-wide association studies (GWAS) have successfully identified many common genetic variants associated with complex diseases over the past decade. The 'gold standard' method for validating the top single nucleotide polymorphisms (SNPs) identified in GWAS is to independently replicate the findings in similar or diverse large-scale external cohorts. However, for rare diseases, it can be difficult to find an external validation cohort within a reasonable timeframe. In such situations, resampling methods, such as the two-step iterative resampling (TSIR) approach have been used to identify SNPs associated with the outcome of interest. However, the TSIR approach involves choosing several parameters in each step, which can influence the performance of the approach. In this paper, we undertook extensive simulation studies to assess the effect of choice of different parameters on the type I error and power for both binary and continuous phenotypes and also compared the TSIR approach with the traditional one-stage (OS) and two-stage (TS) GWAS analysis. We illustrate the usefulness of the TSIR approach by applying it to a GWAS of childhood cancer survivors. Our results indicate that the TSIR approach with an at least 70:30 split and a cutoff of discovering and replicating SNPs at least 20 times in 100 replications provides conservative type I error control and has near 'optimal' power for internally validated SNPs. Its performance is comparable with the TS GWAS for which an external validation cohort is available with only slight reduction in power in some situations. It has almost the same power as OS GWAS with conservative type I error which leads to fewer false positive findings. TSIR is a powerful and efficient method for identifying and internally validating SNPs for GWAS when independent cohorts for external validation may not be available. PMID- 26377240 TI - A pilot study of gene testing of genetic bone dysplasia using targeted next generation sequencing. AB - Molecular diagnosis of genetic bone dysplasia is challenging for non-expert. A targeted next-generation sequencing technology was applied to identify the underlying molecular mechanism of bone dysplasia and evaluate the contribution of these genes to patients with bone dysplasia encountered in pediatric endocrinology. A group of unrelated patients (n=82), characterized by short stature, dysmorphology and X-ray abnormalities, of which mucopolysacharidoses, GM1 gangliosidosis, mucolipidosis type II/III and achondroplasia owing to FGFR3 G380R mutation had been excluded, were recruited in this study. Probes were designed to 61 genes selected according to the nosology and classification of genetic skeletal disorders of 2010 by Illumina's online DesignStudio software. DNA was hybridized with probes and then a library was established following the standard Illumina protocols. Amplicon library was sequenced on a MiSeq sequencing system and the data were analyzed by MiSeq Reporter. Mutations of 13 different genes were found in 44 of the 82 patients (54%). Mutations of COL2A1 gene and PHEX gene were found in nine patients, respectively (9/44=20%), followed by COMP gene in 8 (18%), TRPV4 gene in 4 (9%), FBN1 gene in 4 (9%), COL1A1 gene in 3 (6%) and COL11A1, TRAPPC2, MATN3, ARSE, TRPS1, SMARCAL1, ENPP1 gene mutations in one patient each (2% each). In conclusion, mutations of COL2A1, PHEX and COMP gene are common for short stature due to bone dysplasia in outpatient clinics in pediatric endocrinology. Targeted next-generation sequencing is an efficient way to identify the underlying molecular mechanism of genetic bone dysplasia. PMID- 26377242 TI - Deletion of 19q13 reveals clinical overlap with Dubowitz syndrome. AB - Dubowitz syndrome is a presumed autosomal recessive disorder characterized by multiple congenital abnormalities: microcephaly, learning and developmental delay, growth failure, and a predisposition to allergies and eczema. There have been more than 150 individuals reported to have this diagnosis, but no unifying genetic alteration has been identified indicating genetic heterogeneity. We report on a pair of monozygotic twins diagnosed clinically with Dubowitz syndrome by Professor Dubowitz over 30 years ago and identified to have a de novo heterozygous 3.2-Mb deletion at 19q13.11q13.12. Exome sequencing did not identify either a putative pathogenic variant on the trans allele supporting recessive inheritance or any other causative sequence variants. Comparison of the phenotype in our cases shows considerable overlap with the 19q13.11 microdeletion syndrome, suggesting that a subset of individuals diagnosed with Dubowitz syndrome may be due to deletions at 19q13. Our finding further reinforces the genetic and phenotypic heterogeneity of Dubowitz syndrome. PMID- 26377243 TI - Genome- and exome-wide association study of serum lipoprotein (a) in the Jackson Heart Study. AB - Lipoprotein (a) (Lp(a)) is an independent risk factor for cardiovascular disease. Lp(a) levels in African Americans (AAs) are much higher compared with that in European Americans. We conducted a genome- and an exome-wide association study of Lp(a) among 2895 AAs participating in the Jackson Heart Study. We observed that local ancestry at 6q25.3 was an important risk factor for Lp(a) in AAs, and that multiple single-nucleotide polymorphisms (SNPs) at the well-established LPA locus were significantly associated with Lp(a) (P<5 * 10(-8)) after adjusting for the local ancestry at 6q25.3. Interestingly, before adjusting for local ancestry, we observed significant (P<5 * 10(-8)) associations for hundreds of SNPs spanning ~10 Mb region on 6q surrounding the LPA gene, whereas after adjusting for local ancestry, the region containing significantly associated SNPs got much narrower and was centered over the LPA gene (<1 Mb). We observed a single nonsynonymous SNP in APOE significantly associated with Lp(a) (P<5 * 10(-8)). A high burden of coding variants in LPA and APOE were also associated with higher Lp(a) levels. Our study provides evidence that ancestry-specific causal risk variant(s) resides in or near LPA and that most of the observed associations outside this narrower region are spurious associations. PMID- 26377244 TI - Platelet Dysfunction in Patients with Chronic Myeloid Leukemia: Does Imatinib Mesylate Improve It? AB - OBJECTIVE: The aim of this study was to investigate the effects of imatinib mesylate on platelet aggregation and adenosine triphosphate (ATP) release in chronic myeloid leukemia patients. MATERIALS AND METHODS: Platelet aggregation and ATP release induced by 5.0 mM adenosine diphosphate, 0.5 mM arachidonic acid, 1.0 mg/mL ristocetin, and 2 ug/mL collagen were studied by whole blood platelet lumi-aggregometer in 20 newly diagnosed chronic myeloid leukemia patients before and after imatinib mesylate treatment. RESULTS: At the time of diagnosis, 17/20 patients had abnormal platelet aggregation results; 8 (40%) had hypoactivity, 6 (30%) had hyperactivity, and 3 (15%) had mixed hypo- and hyperactivity. Repeat platelet aggregation studies were performed after a mean of 19 months (min: 5 months-max: 35 months) in all patients who received imatinib mesylate during this period. After therapy, 18/20 (90%) patients had abnormal laboratory results; 12 (60%) had hypoactive platelets, 4 (20%) had mixed hypo- and hyperactive platelets, and 2 (10%) had hyperactive platelets. Three of the 8 patients with initial hypoactivity remained hypoactive, while 2 developed a mixed picture, 2 became hyperactive, and 1 normalized. Of the 6 patients with initial hyperactivity, 4 became hypoactive and 2 developed a mixed pattern. All of the 3 patients with initial hypo- and hyperactivity became hypoactive. Finally, 2 of the 3 patients with initial normal platelets became hypoactive while 1 remained normal. There was a significant decrease in ristocetin-induced platelet aggregation after therapy (p<0.001), while platelet aggregation and secretion induced by other agonists showed no difference after treatment (p>0.05). CONCLUSION: These findings indicate that a significant proportion of chronic myeloid leukemia patients have different patterns of platelet function abnormalities and imatinib mesylate has no effect on these abnormalities, with a significant impairment in ristocetin-induced platelet aggregation. PMID- 26377245 TI - A Bio-inspired Approach for Chromophore Communication: Ligand-to-Ligand and Host to-Guest Energy Transfer in Hybrid Crystalline Scaffolds. AB - Efficient multiple-chromophore coupling in a crystalline metal-organic scaffold was achieved by mimicking a protein system possessing 100% energy-transfer (ET) efficiency between a green fluorescent protein variant and cytochrome b562. The two approaches developed for ET relied on the construction of coordination assemblies and host-guest coupling. Based on time-resolved photoluminescence measurements in combination with calculations of the spectral overlap function and Forster radius, we demonstrated that both approaches resulted in a very high ET efficiency. In particular, the observed ligand-to-ligand ET efficiency value was the highest reported so far for two distinct ligands in a metal-organic framework. These studies provide important insights for the rational design of crystalline hybrid scaffolds consisting of a large ensemble of chromophore molecules with the capability of directional ET. PMID- 26377246 TI - Fabrication of Cd(II)-MOF-based ternary photocatalytic composite materials for H2 production via a gel-to-crystal approach. AB - Cd(II)-MOF-based ternary composite materials of CdS@Cd(II)-MOF@TiO2 were prepared by a unique TiO2 induced gel-to-crystal approach. CdS@Cd(II)-MOF@TiO2 was demonstrated to be a highly active photocatalyst for hydrogen production under visible light based on water photolysis. PMID- 26377247 TI - Hydrophilic interaction liquid chromatography coupled with tandem mass spectrometry method for the simultaneous determination of l-valine, l-leucine, l isoleucine, l-phenylalanine, and l-tyrosine in human serum. AB - l-Valine, l-leucine, l-isoleucine, l-phenylalanine, and l-tyrosine are important proposed biomarkers for the early detection and diagnosis of type 2 diabetes. A simple and selective hydrophilic interaction chromatography with tandem mass spectrometry method was developed for the simultaneous determination of these amino acids in human serum, using stable isotope-labeled amino acids as internal standards. Chromatographic separation was carried out on a Syncronis HILIC column (150 mm * 2.1 mm, 5 MUm) with the column temperature of 35 degrees C and a mobile phase consisted of acetonitrile/120 mM ammonium acetate (89:11, v/v), and the run time was 11.0 min. The mass spectrometric analysis was performed using a QTRAP 5500 mass spectrometer coupled with an electrospray ionization source in positive ion mode. As these five amino acids are endogenous compounds in serum, we used the corresponding stable isotope-labeled amino acids to evaluate the matrix effect and recovery in serum. The matrix effect was 98.7-107.3%, and the recovery was 92.7-102.3%. Calibration curves spiked unlabeled amino acids in water were linear over the range of 0.200-100 MUg/mL. The accuracy, inter-, and intraday precision were below 10.2%. Analytes were stable during the study. This assay method has been validated and applied to the early diagnosis research of type 2 diabetes. PMID- 26377248 TI - Ustekinumab as therapy for psoriasis in a 2-year-old girl. PMID- 26377249 TI - Short-Term Responses of Ground-Dwelling Beetles to Ice Storm-Induced Treefall Gaps in a Subtropical Broad-Leaved Forest in Southeastern China. AB - Periodic natural disturbances shape the mosaic character of many landscapes and influence the distribution and abundance of organisms. In this study, we tested the effect of ice storm-induced treefall gaps on ground-dwelling beetle assemblages in different-aged successional stands of subtropical broad-leaved forest in southeastern China. We evaluated the relative importance of gap-phase microhabitat type (within gap, gap edge, and interior shaded) within different stand ages (regenerating stands and mature stands) as determinants of changes in beetle diversity and community structure. At 18 replicate sites sampled during 2009-2010, no significant differences were found in species richness and the abundances of the most common beetle species captured in pitfall traps among the three gap-phase microhabitat types, but the abundances of total beetles, as well as fungivorous and phytophagous species groups, were significantly lower in gap microhabitats than in interior shaded microhabitats in mature stands. Beetle assemblage composition showed no significant differences among the three microhabitat types, and only the fauna of gap plots slightly diverged from those of edge and shaded plots in mature stands. Cover of shrubs and stand age significantly affected beetle assemblage structure. Our results suggest that beetle responses to gap-phase dynamics in early successional forests are generally weak, and that effects are more discernible in the mature stands, perhaps due to the abundance responses of forest-specialist species. PMID- 26377250 TI - Bullous Sweet's Syndrome: Report of an Atypical Case Presenting with Ring-Like, Figurate Lesions. PMID- 26377251 TI - Comment: Toward a physiology of eating disorder in frontotemporal dementia. PMID- 26377252 TI - Eating behavior in frontotemporal dementia: Peripheral hormones vs hypothalamic pathology. AB - OBJECTIVE: To contrast the relationships of hormonal eating peptides and hypothalamic volumes to eating behavior and metabolic changes (body mass index [BMI]) in behavioral variant frontotemporal dementia (bvFTD) and semantic variant primary progressive aphasia (svPPA). METHODS: Seventy-five patients with dementia (19 bvFTD, 26 svPPA, and 30 Alzheimer disease dementia) and 23 controls underwent fasting blood analyses of leptin, ghrelin, cholecystokinin, peptide tyrosine tyrosine (PYY), and agouti-related peptide (AgRP) levels. On brain MRI anterior, posterior, and total hypothalamic volumes were measured. Relationships between endocrine measures, hypothalamic volumes, eating behaviors, and BMI were investigated. RESULTS: Levels of AgRP were higher in patients with bvFTD (69 +/- 89 pg/mL) and svPPA (62 +/- 81 pg/mL) compared with controls (23 +/- 19 pg/mL, p < 0.01). No differences were found for leptin, oxytocin, cholecystokinin, ghrelin, and PYY levels. Patients with bvFTD and svPPA had higher scores on questionnaires measuring eating behaviors. Atrophy of the posterior and total hypothalamus was observed in the bvFTD group only. Linear regression modeling revealed that leptin and AgRP levels predicted BMI. CONCLUSION: Eating abnormalities are multifactorial in FTD. In bvFTD, they are in part related to hypothalamic degeneration, with potential disintegration of the network connections between the hypothalamus and orbitofrontal cortex/reward pathways. In svPPA, although hypothalamic volumes are preserved, this group experiences elevated AgRP levels similar to bvFTD, which predicts BMI in both groups. This finding highlights the potential key role of AgRP in eating and metabolic changes and provides a potential target for treatment to modify disease progression. PMID- 26377253 TI - Body mass index, physical activity, and risk of adult meningioma and glioma: A meta-analysis. AB - OBJECTIVE: Whether adiposity and lack of physical activity affect the risk for developing meningioma and glioma is poorly understood. Our objective was to characterize these associations in detail. METHODS: We conducted a systematic review and meta-analysis of adiposity and physical activity in relation to meningioma and glioma using cohort and case-control studies published through February 2015. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: We identified 12 eligible studies of body mass index (BMI) and 6 studies of physical activity, comprising up to 2,982 meningioma cases and 3,057 glioma cases. Using normal weight as the reference group, overweight (summary relative risk [RR] = 1.21, 95% confidence interval [CI] = 1.01-1.43) and obesity (RR = 1.54, 95% CI = 1.32-1.79) were associated with increased risk of meningioma. In contrast, overweight (RR = 1.06, 95% CI = 0.94-1.20) and obesity (RR = 1.11, 95% CI = 0.98-1.27) were unrelated to glioma. Similarly, dose-response meta-analyses revealed a statistically significant positive association of BMI with meningioma, but not glioma. High vs low physical activity levels showed a modest inverse relation to meningioma (RR = 0.73, 95% CI = 0.61-0.88) and a weak inverse association with glioma (RR = 0.86, 95% CI = 0.76-0.97). Relations persisted when the data were restricted to prospective studies, except for the association between physical activity and glioma, which was rendered statistically nonsignificant (RR = 0.91, 95% CI = 0.77 1.07). CONCLUSIONS: Adiposity is related to enhanced risk for meningioma but is unassociated with risk for glioma. Based on a limited body of evidence, physical activity is related to decreased risk of meningioma but shows little association with risk of glioma. PMID- 26377254 TI - Time trends in incidence, case fatality, and mortality of intracerebral hemorrhage. AB - OBJECTIVE: To assess age- and sex-specific trends in incidence and 30-day and 1 year case fatality of intracerebral hemorrhage (ICH) in the Netherlands. METHODS: Patients hospitalized for first ICH were identified through linkage of the national hospital discharge register and population register using ICD-9 code 431. We identified out-of-hospital deaths in the national cause of death register. Incidence, 30-day and 1-year case fatality, and total mortality rate were calculated by age and sex. We identified time trends by joinpoint regression analysis and Mann-Kendall tests. RESULTS: We identified 41,068 cases of ICH (51% men) between 1998 and 2010, of which 6% were out-of-hospital deaths. ICH incidence declined in men and women younger than 75 years (p <= 0.01, not significantly in men 35-54 years) but remained stable in patients 75 years and older. Thirty-day and 1-year case fatality declined in patients younger than 75 years (not significantly in women 35-54 years). In patients aged 35 to 54 years, ICH mortality remained stable until 2003 and then declined slightly (annual percentage change [APC] men: -7.09%; 95% confidence interval [CI] -11.39 to 2.59; women: -8.67%; 95% CI -15.18 to -1.66). In patients 55 to 74 years, mortality declined in men between 1995 and 2010 (APC -4.55%; 95% CI -5.49 to 3.59) and in women between 1992 and 2010 (APC -3.51%; 95% CI -4.16 to -2.85). Mortality did not decline in patients aged 75 years and older. CONCLUSION: In the Netherlands, ICH incidence, case fatality, and mortality rates have declined significantly in men and women younger than 75 years but remained stable in patients 75 years and older. The observed time trends may be explained by better prevention and treatment during the previous 2 decades of which the elderly do not seem to benefit. PMID- 26377255 TI - Correlation between blend morphology and recombination dynamics in additive-added P3HT:PCBM solar cells. AB - The addition of a small amount of high boiling point solvent in organic donor/acceptor blends to control their morphology is a viable approach to enhance the power conversion efficiency of bulk heterojunction (BHJ) organic solar cells. Herein, through transient absorption spectroscopy (TAS) correlated with physical characterizations and device studies, we investigate the effects of a family of thiol-based additives (i.e., 1,5-pentanedithiol (PDT), 1,6-hexanedithiol (HDT) and 1,8-octanedithiol (ODT)) in P3HT:PCBM blend films in a bid to establish a morphology-function-charge dynamics relationship with their photovoltaic performances. The performance of solar cell devices (etaHDT = 2.8%, etaODT = 2.8%, etaPDT = 1.7%) is related to the additive-induced phase separation and the degree of ordering of P3HT. TAS uncovers a more efficient initial exciton and polaron generation in the additive-treated blend samples compared to the non additive treated control sample. HDT and ODT-added blends exhibit decay dynamics and performances similar to those of the thermally annealed samples. However, the PDT-added blend exhibits a strong trap-assisted recombination in the subsequent nanosecond-microsecond timescales. We attribute this to the loss of charge carriers in the larger isolated P3HT domains due to the lack of percolation paths to the electrode. Our findings illustrate that understanding the complex interplay of the crystalline order, intermixed phases and percolation pathways is key to optimizing the performance of thermal-annealing free, additive-treated organic solar cells. PMID- 26377257 TI - Systemic to Pulmonary Artery Versus Right Ventricular to Pulmonary Artery Shunts for Patients With Pulmonary Atresia, Ventricular Septal Defect, and Hypoplastic Pulmonary Arteries. AB - OBJECTIVE: The systemic-pulmonary shunts (SPS) and the right ventricle to pulmonary artery connection (RV-PA connection) are two palliative procedures for patients with pulmonary atresia, ventricular septal defect, and hypoplastic pulmonary arteries. Our aim is to compare early and midterm outcomes of these two procedures. METHODS: Clinical data of 132 consecutive patients with PA/VSD who underwent the SPS or the RV-PA connection in Fuwai Hospital from January 2011 to June 2014 were retrospectively analyzed. Patients were divided into two groups according to the procedures. Early outcomes including duration of ventilation, length of intensive care unit (ICU) stay, complication incidence, and improvements in oxygen saturation (SpO2 ) were compared. Midterm outcomes including improvement on Nakata index and complete repair rate were evaluated. Death and complete repair were considered as the end-points. RESULTS: 80 patients underwent SPS, 52 patients underwent RV-PA connection. There were three early deaths and six late deaths in SPS group, while there was no early deaths and only one late death in the RV-PA connection group. For the early outcomes, the SO2 increase after RV-PA connection was significantly higher than that SO2 increase after SPS (20% vs. 15%, p < 0.001). There was no statistical difference in length of ICU stay, duration of ventilatory support, or rate of postoperative complications (all p > 0.05) between the SPS group and RV-PA connection group. The incidence of severe postoperative complications and redo-sternotomy rate of the SPS group was significantly higher than that of the RV-PA connection group (12.5% vs. 1.9% [p = 0.018], 11.3% vs. 1.9%, [p = 0.031]). For the median outcomes, the mean follow-up was 2.3 (0.6-4) years. No statistical difference on Nakata index increase (74.1 +/- 23.4 mm(2) /m(2) vs. 84.2 +/- 48.7 mm(2) /m(2) , p = 0.350) and the complete repair rate (37.2% vs. 42.5%, p = 0.581) was found between the two groups, but the interphase between the initial procedure and complete repair was shorter in RV-PA connection group than that in the SPS group (11.8 +/- 3.5m vs. 16.8 +/- 8.5 m, p = 0.038). CONCLUSION: There is a significant improvement in oxygen saturation and a more stable perioperative course for patients with RV-PA connection. There is also a shorter interval from the initial procedure to complete repair and a lower mortality after RV-PA connection. PMID- 26377258 TI - Secondary Neoplasms in Children with Hodgkin's Lymphoma Receiving C-MOPP and Radiotherapy: Presentation of Four Cases. AB - Patients who survive Hodgkin lymphoma (HL) are at increased risk of secondary neoplasms (SNs). A wide variety of SNs have been reported, including leukemias, non-Hodgkin's lymphomas, and solid tumors, specifically breast and thyroid cancers. Herein we report subsequent neoplasms in four patients with HL receiving chemoradiotherapy. It is interesting that three SNs, fibrosarcoma, thyroid carcinoma, and retrobulbar meningioma, were observed in the radiation area in one of our patients. A hypopharyngeal epithelioid malignant peripheral nerve sheath tumor as an unusual secondary malignant neoplasm developed in another patient, while a benign thyroid nodule and invasive ductal breast carcinoma were observed at different times in the female patient. Follicular adenoma of the thyroid gland developed in one of our patients. PMID- 26377259 TI - Effect of Exposure Dose on Ichthyophonus Prevalence and Infection Intensity in Experimentally Infected Rainbow Trout, Oncorhynchus mykiss. AB - This study describes the effect of increasing exposure dose on Ichthyophonus prevalence and infection intensity in experimentally infected rainbow trout, Oncorhynchus mykiss. Specific-pathogen free trout were exposed per os to increasing numbers of Ichthyophonus schizonts obtained from naturally infected donor fish, then sampled after 30 and 60 days post-exposure. Both in vitro explant culture and histology revealed that as the number of schizonts per dose increased there was a proportionate increase in the number of infected fish, as well as an increase in the number of infected organs; parasite density in individual infected organs also increased with dose. Explant culture revealed that all fish exposed to the highest dose (>=2,080 schizonts) became infected, while only 67% of those exposed to the intermediate dose (1,040-1,153 schizonts) were Ichthyophonus-positive after 60 days; Ichthyophonus was not detected in fish exposed to the 2 lowest doses (<=280 schizonts). Histologic examination of individual infected organs also revealed increasing infection prevalence and parasite density in response to exposure to increasing numbers of Ichthyophonus schizonts. PMID- 26377260 TI - Flat detector C-arm CT-guidance system in performing percutaneous transthoracic needle biopsy of small (<=3 cm) pulmonary lesions. AB - BACKGROUND: Nowadays, flat detector (FD) equipped angiographic C-arm computed tomography (CACT) systems can be used to acquire CT-like cross-sectional images directly within the interventional suite. The CACT systems offer real time visualization of transthoracic needle biopsy (TNB) procedure and more flexibility in the orientation of the detector system around the patient compared to traditional CT systems. PURPOSE: To evaluate the value of a flat detector C-arm CT-guidance system in performing percutaneous transthoracic needle biopsy (PTNB) for small (<=3 cm) pulmonary lesions in clinical practice. MATERIAL AND METHODS: A total of 60 patients with solid lung lesions were retrospectively enrolled to undergo PTNB procedures. The mean diameter of lesions was 2.3 +/- 0.6 cm (range, 0.6-3 cm). The needle path was carefully planned and calculated on the C-arm CT system, which acquired three-dimensional CT-like cross-sectional images. The PTNB procedures were performed under needle guidance with fluoroscopic feedbacks. RESULTS: Histopathologic tissue was successfully obtained from 59 patients with a puncture success rate of 98.3% (59/60). The diagnostic accuracy rate was found to be 91.5% (54/59). There were only two cases of pneumothorax (3.3%) requiring therapy. The rates of pneumothorax and hemoptysis were low (15.0% [9/60] and 8.3% [5/60], respectively). The overall procedural time was in the range of 12-18 min, resulting in a mean exposure dose of 224.4 +/- 4.8 mGy. CONCLUSION: Our study shows that C-arm CT-based needle guidance enables reliable and efficient needle positioning and progression by providing real-time intraoperative guidance for small (<=3 cm) pulmonary lesions in clinical practice. PMID- 26377256 TI - Early-life exposures to infectious agents and later cancer development. AB - There is a growing understanding that several infectious agents are acquired in early life and this is the reason why available vaccines target the new born, infants, and adolescents. Infectious agents are associated with cancer development and it is estimated that about 20% of the world's cancer burden is attributed to infectious agents. There is a growing evidence that certain infectious agents acquired in early life can give rise to cancer development, but estimates of the cancer burden from this early-life acquisition is unknown. In this article, we have selected five cancers (cervical, liver, Burkitt's lymphoma leukemia, nasopharyngeal carcinoma, and adult T-cell leukemia-lymphoma) and examine their links to infectious agents (HPV, HBV, HCV, EBV, and HTLV-1) acquired in early life. For these agents, the acquisition in early life is from mother-to-child transmission, perinatal contact (with genital tract secretions, amniotic fluids, blood, and breast milk), saliva, sexual intercourse, and blood transfusion. We also discuss prevention strategies, address future directions, and propose mechanisms of action after a long latency period from the time of acquisition of the infectious agent in early life to cancer development. PMID- 26377261 TI - Variation of bilateral transverse ligament tubercles with age and gender in a large series of subjects on multidetector computed tomography. AB - BACKGROUND: The transverse ligament tubercles play an important role in maintaining the stability of upper cervical spine, but the variation of these tubercles with aging has not been studied systematically. PURPOSE: To evaluate the variation of the height of the transverse ligament tubercles with respect to age and gender, and assess side-to-side differences on multidetector computed tomography (MDCT). MATERIAL AND METHODS: A consecutive series of 291 Chinese patients undergoing a head or neck MDCT were divided into eight age groups. The bony anatomy of the atlas was displayed symmetrically by aligning the axial plane and the mean height of bilateral transverse ligament tubercles was measured. The height was correlated with age and gender and side-to-side differences were analyzed. Finally, the inter-observer performance was assessed. RESULTS: No transverse ligament tubercles were seen in 51 cases (17.5%, 51/291) and unilateral transverse ligament tubercles were seen in two cases (0.7%, 2/291). Bilateral transverse ligament tubercles were observed in 238 cases (81.8%, 238/291). The average height of the left and right tubercles were 2.68 +/- 1.58 mm and 2.68 +/- 1.54 mm, respectively, with no significant side-to-side differences (t = 0.061, P > 0.05). The height was also similar in both genders (left: t = 0.497, P > 0.05, right: t = 0.730, P > 0.05). The height increased linearly with age (left: r = 0.513, P < 0.05, right: r = 0.516, P < 0.05). The inter-observer reliability was excellent. CONCLUSION: The height of the transverse ligament tubercles on MDCT linearly increases with increasing age with no significant differences among the genders or the side measured. PMID- 26377262 TI - Objective measurement of the distal resection margin by MRI of the fresh and fixed specimen after partial mesorectal excision for rectal cancer: 5 cm is not just 5 cm and depends on when measured. AB - BACKGROUND: Most studies have directly established the optimal perioperative in situ clearance margin in surgery for rectal cancer from the histologically observed extent of distal spread, neglecting the tissue variability that occurs after resection and fixation of the rectal specimen. PURPOSE: To measure the length of the distal resection margin in the fresh and fixed specimen following partial mesorectal excision for rectal cancer using magnetic resonance imaging (MRI) to document tissue shrinkage after surgical removal and fixation. MATERIAL AND METHODS: The length of the distal resection margin was measured by MRI of the fresh and fixed specimen and at histopathological examination of the fixed specimen in 10 patients who underwent surgery for upper rectal cancer. In addition, tissue shrinkage was estimated by measuring the total length of the fresh and fixed specimen and distance from the peritoneal reflection anteriorly to the distal cut edge of the specimen. RESULTS: Measured by MRI, the distal resection margin was in the range of 0.6-10.2 cm (mean, 4.6 cm) in the fresh specimen, and 0.5-6.2 cm (mean, 3.2 cm) in the fixed specimen. The tissue shrinkage ratio was a mean of 69% (interquartile range, 61-77%). Taking all ratios from MRI and histopathological examination of tissue shrinkage into account, the collective tissue shrinkage ratio was 70% (95% confidence interval, 67-73%) CONCLUSION: The length of the distal resection margin was reduced by 30% after surgical removal and fixation of the specimen. PMID- 26377263 TI - The phase value of putamen measured by susceptibility weighted images in Parkinson's disease and in other forms of Parkinsonism: a correlation study with F18 FP-CIT PET. AB - BACKGROUND: Iron deposition of basal ganglia in Parkinson's disease (PD) can be measured using susceptibility weighted images (SWI) on magnetic resonance imaging (MRI). Fluoropropyl carbomethoxy-3b-4-iodophenyltropane (F18 FP-CIT) positron emission tomography (PET) has been used to differentiate Parkinsonism. PURPOSE: To compare SWI phase values in Parkinsonian syndrome and age-matched control and to correlate them with F18 FP-CIT PET. MATERIAL AND METHODS: Retrospectively, patients with Parkinsonian movement disorder (n = 62) and age-matched control (n = 16) were enrolled. Mean phase values on SWI were measured by region of interest (ROI) in putamens and caudate heads. Mean standardized uptake value (SUV) on F18 FP-CIT were measured in the same ROIs of PD (n = 40) and other forms of Parkinsonism (n = 22). A statistical analysis was performed to compare the phase values and SUVs and to correlate them between groups. RESULTS: The putaminal mean phase values were higher in Parkinsonism than in the control (P <= 0.001). There was no difference of phase value in caudate head among the groups. Also, the mean phase value of putamen between PD and other forms of Parkinsonism was not different. Mean SUV of F18 FP-CIT in the putamen was lower in PD than other forms of Parkinsonism (P <= 0.014). However, there was no significant correlation between phase values and mean SUV (P > 0.05). CONCLUSION: The putaminal phase value was higher than in Parkinsonian syndrome than in the age-matched controls. F18 FP-CIT PET/CT showed different tracer activity between PD and other forms of Parkinsonism. However, no correlation between phase and SUV values was discovered. PMID- 26377264 TI - Relationships Between Self-Reported Leadership Practices, Job Satisfaction, and Demographics of Radiology Administrators. AB - PURPOSE: To evaluate the self-reported leadership practices of radiology administrators and the demographic characteristics associated with those leadership practices. The effect of these demographic characteristics and leadership practices on job satisfaction also was studied. METHODS: One-hundred forty-nine American Society of Radiologic Technologists members who indicated they have a position of administrator/manager, chief technologist, or supervisor completed a demographic survey and the Leadership Practices Inventory (LPI) self survey tool. The LPI divides successful leadership into 5 practices: Challenge the Process, Inspire a Shared Vision, Enable Others to Act, Encourage the Heart, and Model the Way. RESULTS: The categories Challenge the Process and Inspire a Shared Vision had the lowest mean scores and the widest variation. Having had formal leadership training and being older were demographic characteristics associated with higher LPI scores. Having a higher LPI score and having had formal leadership training were associated with higher job satisfaction. DISCUSSION: Formal leadership training was the only statistically significant variable when using LPI score as the response variable. CONCLUSION: The results of this study show that radiology administrators would benefit from formal leadership training that focuses on challenging the process and inspiring a shared vision. PMID- 26377265 TI - 3-D Isotropic MR Imaging for Planning Bone Reconstruction in Patients With Femoroacetabular Impingement. AB - BACKGROUND: Femoroacetabular impingement (FAI) is commonly seen in young or middle-aged patients. Early detection and correction of FAI-related bony deformities or pelvic realignment are essential to prevent the development or progression of hip osteoarthritis. DISCUSSION: Computed tomography (CT) and magnetic resonance (MR) imaging are the reference standards for the evaluation of bony anatomy and treatable internal derangement findings of the hip, respectively. Surgeons prefer CT imaging for preoperative bone delineation because of its 3-D isotropic capabilities and excellent multiplanar reconstructions. Three-Tesla (3T) MR scans enable high-resolution 3-D MR reconstructions for bone depiction similar to 3-D CT reconstructions and have the potential to eliminate the need for duplicate (CT and MR) scanning. CONCLUSION: This technical report illustrates the feasibility of such an approach and compares bone rendering obtained using isotropic data from 3-D MR with 3-D CT in the same patient. PMID- 26377266 TI - Radiographers' Ability to Detect Low-Contrast Detail in Digital Radiography Systems. AB - PURPOSE: To evaluate radiographers' ability to detect low-contrast detail using various digital planar radiographic systems. METHODS: A low-contrast detail phantom was placed between two 5-cm thick Perspex sheets (Lucite International). Images were obtained using different kilovoltage peak and milliamperage second (mAs) settings with computed radiography (CR), indirect conversion digital radiography (IDR), and direct conversion digital radiography (DR) systems. Six groups of 6 radiographers were asked to score 39 images; each group scored 2 images from each system for a total of 6 images. The seventh group scored only one image from each system for a total of 3 images. The radiographers' results were compared with the results of analyzer software. The inverse image quality factor was used to measure low-contrast detail detectability performance. RESULTS: Radiographers performed significantly worse than the computerized software in determining low-contrast detail in planar radiographic images (P < .01). However, a positive correlation (R = 0.558) existed between the 2 sets of scores in terms of low-contrast detail detectability performance. DISCUSSION: On average, radiographers were able to detect increased image quality resulting from increased mAs. Radiographers reached results similar to the software regarding whether IDR and DR have better detectability performances than CR. Differences found among individual radiographers were not as significant with DR. CONCLUSION: When radiographers' performance in detecting low-contrast detail was evaluated and compared with that of the software, radiographers exhibited poorer performances. Because radiographers are responsible for image quality optimization, additional training might improve their ability to detect low contrast detail in DR systems. PMID- 26377267 TI - Emergency Chest Imaging. AB - This article presents the anatomy of the chest, heart, and upper airway and describes types of traumatic pathology and injuries of the chest. Chest imaging in a variety of settings is described. Radiography, computed tomography, and ultrasonography are discussed, along with the benefits and limitations of each modality. Finally, promising technological developments that could aid chest imaging in emergent situations are reviewed. PMID- 26377268 TI - Total Knee Replacement and Imaging. AB - Total knee replacement (total knee arthroplasty) is performed to restore function and relieve pain in patients with severely damaged knees. The surgery involves replacement of both the medial and lateral femorotibial joints and the patellofemoral joint. Although total knee replacement is an effective treatment, postoperative complications include blood clots, infection, and loosening or malalignment of the prosthetic component. Medical imaging plays a critical role in preoperative evaluation, surgical planning, and followup. PMID- 26377269 TI - Imaging C7 Through T1 . PMID- 26377270 TI - Exceptional Report. PMID- 26377271 TI - Radiologic Science Faculty Needs Assessment. PMID- 26377272 TI - The Importance of Accurate Patient History and Imaging Correlation Prior to Ordering Additional Imaging: A Case Study. PMID- 26377273 TI - Distance Education Standards. PMID- 26377274 TI - Health Literacy: Implications and Strategies. PMID- 26377275 TI - Magnetic Resonance Safety Practices: The New Normal. PMID- 26377276 TI - Staff Technologist to Clinical Instructor: Using the Clinical Instructor Academy. PMID- 26377277 TI - Publication Takes Patience: Revision and Resubmission. PMID- 26377278 TI - Blunt Trauma. PMID- 26377280 TI - Utilization of methylarenes as versatile building blocks in organic synthesis. AB - The development of practical and efficient methods for C-C and C-X bond formation has attracted a great deal of current attention with the advent of C-H functionalization reactions. Hydrocarbons are perhaps the most inexpensive and readily available materials, and utilisation of such materials for the synthesis of essential chemicals is virtually and economically pragmatic. The means to utilize easily accessible hydrocarbons not only represents a useful, potent and straightforward alternative, but also constitutes an excellent opportunity to improve our chemical knowledge about a relatively unexplored domain. Early examples using alkylarenes are generally limited to their conversion to aldehydes, carboxylic acids, and nitriles. This review intends to focus on the latest developments adopting modern strategies for sp(3) C-H functionalization of methylarenes to achieve a diverse range of important organic compounds. PMID- 26377279 TI - Breast Imaging Artifacts. AB - Artifacts appear on breast images for a number of reasons. Radiologic technologists play an important role in identifying artifacts that can help or hinder breast cancer diagnosis and in minimizing artifacts that degrade image quality. This article describes various artifacts that occur in breast imaging, along with their causes. The article focuses on artifacts in mammography, with a heavy emphasis on digital mammography, and on magnetic resonance imaging of the breast. Artifacts in ultrasonography of the breast, digital breast tomosynthesis, and positron emission mammography also are discussed. PMID- 26377281 TI - Two distinct phenotypes of asthma in elite athletes identified by latent class analysis. AB - INTRODUCTION: Clusters of asthma in athletes have been insufficiently studied. Therefore, the present study aimed to characterize asthma phenotypes in elite athletes using latent class analysis (LCA) and to evaluate its association with the type of sport practiced. METHODS: In the present cross-sectional study, an analysis of athletes' records was carried out in databases of the Portuguese National Anti-Doping Committee and the Norwegian School of Sport Sciences. Athletes with asthma, diagnosed according to criteria given by the International Olympic Committee, were included for LCA. Sports practiced were categorized into water, winter and other sports. RESULTS: Of 324 files screened, 150 files belonged to asthmatic athletes (91 Portuguese; 59 Norwegian). LCA retrieved two clusters: "atopic asthma" defined by allergic sensitization, rhinitis and allergic co-morbidities and increased exhaled nitric oxide levels; and "sports asthma", defined by exercise-induced respiratory symptoms and airway hyperesponsiveness without allergic features. The risk of developing the phenotype "sports asthma" was significantly increased in athletes practicing water (OR = 2.87; 95% CI [1.82-4.51]) and winter (OR = 8.65; 95% CI [2.67-28.03]) sports, when compared with other athletes. CONCLUSION: Two asthma phenotypes were identified in elite athletes: "atopic asthma" and "sports asthma". The type of sport practiced was associated with different phenotypes: water and winter sport athletes had three- and ninefold increased risk of "sports asthma". Recognizing different phenotypes is clinically relevant as it would lead to distinct targeted treatments. PMID- 26377283 TI - Paramedics and scope of practice. PMID- 26377282 TI - Effect of valproic acid combined with therapeutic hypothermia on neurologic outcome in asphyxial cardiac arrest model of rats. AB - BACKGROUNDS: Valproic acid (VPA) has been reported to have survival and neuroprotective effects in a cardiac arrest rat model. This study was designed to investigate the effect of VPA combined with therapeutic hypothermia (HT) in an asphyxial cardiac arrest rat model. METHODS: Rats were subjected to 6 minutes of asphyxial cardiac arrest. Cardiopulmonary resuscitation was performed and then the randomly allocated to 1 of 4 groups (normal saline [NS]/normothermia [NT], VPA/NT, NS/HT, and VPA/HT). Hypothermia (32.5 degrees C +/- 0.5 degrees C, 4 hours of HT and 2 hours of rewarming) or NT (37 degrees C +/- 0.5 degrees C for 6 hours) was applied, and VPA (300 mg/kg) or NS was administered immediately after the return of spontaneous circulation. Neurologic deficit score was measured, and a tape removal test was performed for 3 days. Histologic injury of hippocampus was evaluated. RESULTS: Valproic acid significantly improved neurologic deficit score at 48 and 72 hours in the NT-treated rats and at 72 hours in the HT-treated rats (all P < .05). Although the latency and success rate were not significantly different between the VPA/NT and NS/NT groups, the VPA/HT group showed significantly lower latency and higher success rates compared to the NS/HT group (P < .05). The histologic injury score in the hippocampal CA1 sector was significantly lower in the VPA/NT group than the NS/NT group (P < .05) and showed a tendency to be decreased in the VPA/HT group compared with the NS/HT group (P = .06). CONCLUSION: In an asphyxial cardiac arrest rat model, administration of VPA improved neurologic outcomes and added a neuroprotective effect to HT. PMID- 26377284 TI - Special collection on Indigenous health. PMID- 26377286 TI - Financing options to sustain Medicare: are we committed to universalism? PMID- 26377287 TI - Geographic inequity in healthy food environment and type 2 diabetes: can we please turn off the tap? PMID- 26377288 TI - The Murray to the Mountains Intern Training Program. PMID- 26377289 TI - Pattern of malignant mesothelioma incidence and occupational exposure to asbestos in Western Australia. PMID- 26377290 TI - Sudden sensorineural hearing loss secondary to metronidazole ototoxicity. PMID- 26377291 TI - The AMA Specialist Trainee Survey 2014: a survey of hospital-based specialty trainees and general practice registrars. PMID- 26377292 TI - How changes to the Medicare Benefits Schedule could improve the practice of cardiology and save taxpayer money. AB - Rising health care costs above inflation are placing serious strains on the sustainability of the Australian Medicare system in its current structure. The Medicare Benefits Schedule (MBS), which lists rebates payable to patients for private medical services provided on a fee-for-service basis, is the cornerstone of the Australian health care system. Introduced in the 1980s, the MBS has changed little despite major advances in the evidence base for the practice of cardiology. We outline how we believe sensible changes to the MBS listings for four cardiac services--invasive coronary angiography, computed tomography coronary angiography, stress testing and percutaneous coronary intervention- would improve the clinical practice of cardiology and save substantial amounts of taxpayer money. PMID- 26377293 TI - Lost productive life years caused by chronic conditions in Australians aged 45-64 years, 2010-2030. AB - OBJECTIVES: To estimate (1) productive life years (PLYs) lost because of chronic conditions in Australians aged 45-64 years from 2010 to 2030, and (2) the impact of this loss on gross domestic product (GDP) over the same period. DESIGN, SETTING AND PARTICIPANTS: A microsimulation model, Health&WealthMOD2030, was used to project lost PLYs caused by chronic conditions from 2010 to 2030. The base population consisted of respondents aged 45-64 years to the Australian Bureau of Statistics Survey of Disability, Ageing and Carers 2003 and 2009. The national impact of lost PLYs was assessed with Treasury's GDP equation. MAIN OUTCOME MEASURES: Lost PLYs due to chronic disease at 2010, 2015, 2020, 2025 and 2030 (ie, whole life years lost because of chronic disease); the national impact of lost PLYs at the same time points (GDP loss caused by PLYs); the effects of population growth, labour force trends and chronic disease trends on lost PLYs and GDP at each time point. RESULTS: Using Health&WealthMOD2030, we estimated a loss of 347,000 PLYs in 2010; this was projected to increase to 459,000 in 2030 (32.28% increase over 20 years). The leading chronic conditions associated with premature exits from the labour force were back problems, arthritis and mental and behavioural problems. The percentage increase in the number of PLYs lost by those aged 45-64 years was greater than that of population growth for this age group (32.28% v 27.80%). The strongest driver of the increase in lost PLYs was population growth (accounting for 89.18% of the increase), followed by chronic condition trends (8.28%). CONCLUSION: Our study estimates an increase of 112 000 lost PLYs caused by chronic illness in older workers in Australia between 2010 and 2030, with the most rapid growth projected to occur in men aged 55-59 years and in women aged 60-64 years. The national impact of this lost labour force participation on GDP was estimated to be $37.79 billion in 2010, increasing to $63.73 billion in 2030. PMID- 26377294 TI - The Cardiac Genetics Clinic: a model for multidisciplinary genomic medicine. AB - OBJECTIVES: To describe patient characteristics, standard operating procedure, and uptake of genetic testing at the multidisciplinary Cardiac Genetics Clinic (CGC) at the Royal Melbourne Hospital during its first 6 years. DESIGN: Database exploration of referral diagnoses, sex, number of clinic visits and incidence of genetic testing in a population of individuals attending the CGC. SETTING: Tertiary referral hospital (Royal Melbourne Hospital) providing cardiac genetics services to the state of Victoria. PARTICIPANTS: All individuals initially attending the clinic between July 2007 and July 2013, either as the proband or as an at-risk family member. MAIN OUTCOME MEASURES: Classification of patients into diagnostic categories, number of probands and at-risk relatives assessed, incidence and outcomes of genetic testing. RESULTS: 1170 individuals were seen for the first time over the 6-year period; 57.5% made only one visit. The median age was 39 years. Most were encompassed within four broad diagnostic categories: cardiomyopathy (315 patients), aortopathy (303 patients), arrhythmia disorders (203 patients) and resuscitated cardiac arrest and/or family history of sudden cardiac death (341 patients); eight patients had "other" diagnoses. Genetic testing (mutation detection or predictive testing) was undertaken in 381 individuals (32.6%), and a pathogenic mutation was identified in 47.6% of tests, representing 15.3% of the total population. CONCLUSION: The CGC fulfils an important role in assisting clinicians and patients by reviewing genetic cardiac diagnoses. Clinical practice during the study period moved from a selected candidate gene approach to broader gene panel-based testing. This move to next generation sequencing may increase the detection of mutations and variants of unknown significance. A major contribution by the clinic to the care of these individuals and their families is the provision (or negating) of a diagnosis, and of a plan for managing risks of predictable cardiac disease. PMID- 26377295 TI - Success in Closing the Gap: favourable neonatal outcomes in a metropolitan Aboriginal Maternity Group Practice Program. AB - OBJECTIVES: To report differences in neonatal health outcomes for a community based antenatal program, the Aboriginal Maternity Group Practice Program (AMGPP; the intervention group), compared with two matched control groups eligible for standard antenatal care. DESIGN: Non-randomised intervention study using data from the Western Australian Midwives Notification System. Regression models were used to report adjusted odds ratios (aORs) for defined neonatal health outcomes. SETTING: The AMGPP employed Aboriginal grandmothers, Aboriginal Health Officers, and midwives working in partnership with existing antenatal services to provide care for pregnant Aboriginal women residing in south metropolitan Perth. PARTICIPANTS: 343 women (with 350 pregnancies) who participated in the AMGPP and gave birth between 1 July 2011 and 31 December 2012; historical and contemporary control groups of pregnant Aboriginal women (each including 350 pregnancies), frequency matched for maternal age and gravidity. MAIN OUTCOME MEASURES: Preterm births, birthweight, neonatal resuscitation, neonatal hospital length of stay longer than 5 days. RESULTS: Babies born to AMGPP participants were significantly less likely to be born preterm (AMGPP, 9.1% v historical controls, 15.9% [aOR, 0.56; 95% CI, 0.35-0.92]; v contemporary controls, 15.3% [aOR, 0.75; 95% CI, 0.58 0.95]); to require resuscitation at birth (AMGPP, 17.8% v historical controls, 24.4% [aOR, 0.68; 95% CI, 0.47-0.98]; v contemporary controls, 31.2% [aOR, 0.71; 95% CI, 0.60-0.85]), or to have a hospital length of stay of more than 5 days (AMGPP, 4.0% v historical controls, 11.3% [aOR, 0.34; 95% CI, 0.18-0.64]; v contemporary controls, 11.6% [aOR, 0.56; 95% CI, 0.41-0.77]). CONCLUSION: Participation in the AMGPP in south metropolitan Perth was associated with significantly improved neonatal health outcomes. PMID- 26377296 TI - Crush injury by an elephant: life-saving prehospital care resulting in a good recovery. PMID- 26377297 TI - Beware of blotting paper hallucinogens: severe toxicity with NBOMes. PMID- 26377298 TI - Transplantation of the heart after circulatory death of the donor: time for a change in law? AB - Australia has a shortfall in donated hearts for transplantation. Hearts are usually procured from brain dead donors, but procurement from circulatory dead donors is a potential additional source. However, heart transplantation after circulatory death of the donor may not conform to the dead donor rule. An amendment in law is required to permit heart procurement for transplantation after circulatory death. PMID- 26377300 TI - Ofatumumab maintenance versus observation in relapsed chronic lymphocytic leukaemia (PROLONG): an open-label, multicentre, randomised phase 3 study. AB - BACKGROUND: Ofatumumab is a human anti-CD20 monoclonal antibody that has proven efficacy as monotherapy in refractory chronic lymphocytic leukaemia. We assessed the efficacy and safety of ofatumumab maintenance treatment versus observation for patients in remission after re-induction treatment for relapsed chronic lymphocytic leukaemia. METHODS: This open-label, multicentre, randomised phase 3 study enrolled patients aged 18 years or older from 130 centres in 24 countries who had chronic lymphocytic leukaemia in complete or partial remission after second-line or third-line treatment. Eligible patients had a WHO performance status of 0-2, had a response assessment within the previous 3 months, did not have refractory disease, autoimmune haemolytic anaemia requiring treatment, chronic or active infection requiring treatment, and had not previously received maintenance treatment or autologous or allogeneic stem-cell transplant. Using a randomisation list generated by a central computerised system and an interactive voice recognition system, we randomly assigned (1:1) patients to receive ofatumumab (300 mg followed by 1000 mg 1 week later and every 8 weeks for up to 2 years) or undergo observation. Randomisation was stratified by number and type of previous treatment and remission status after induction treatment (block size of four). Treatment assignment was open label. The primary endpoint was investigator assessed progression-free survival in the intention-to-treat population. We report the results of a prespecified interim analysis after two-thirds of the planned study events (disease progression or death) had happened. This trial is closed to accrual but follow-up is ongoing. This trial is registered with ClinicalTrials.gov, number NCT00802737. FINDINGS: Between May 6, 2010, and June 19, 2014, we enrolled 474 patients: 238 patients were randomly assigned to receive ofatumumab maintenance treatment and 236 to undergo observation. One (<1%) patient in the ofatumumab group did not receive the allocated intervention (withdrawal of consent). The median follow-up was 19.1 months (IQR 10.3-28.8). Progression-free survival was improved in patients assigned to the ofatumumab group (29.4 months, 95% CI 26.2-34.2) compared with those assigned to observation (15.2 months, 11.8-18.8; hazard ratio 0.50, 95% CI 0.38-0.66; p<0.0001). The most common grade 3 or higher adverse events up to 60 days after last treatment were neutropenia (56 [24%] of 237 patients in the ofatumumab group vs 23 [10%] of 237 in the observation group) and infections (31 [13%] vs 20 [8%]). 20 (8%) of 237 patients in the ofatumumab group and three (1%) of 237 patients in the observation group had adverse events that led to permanent discontinuation of treatment. Up to 60 days after last treatment, two deaths related to adverse events occurred in the ofatumumab treatment group and five deaths related to adverse events occurred in the observation group; no deaths were attributed to the study drug. INTERPRETATION: These data are important for the development of optimum maintenance strategies in patients with relapsed chronic lymphocytic leukaemia, notably in the present era of targeted drugs, many of which are to be used until progression. PMID- 26377301 TI - PROLONGing remissions in patients with CLL. PMID- 26377302 TI - Erratum. PMID- 26377303 TI - Electrophoretic behavior of DNA-methyl-CpG-binding domain protein complexes revealed by capillary electrophoreses laser-induced fluorescence. AB - The free solution electrophoretic behavior of DNA-protein complexes depends on their charge and mass in a certain experimental condition, which are two fundamental properties of DNA-protein complexes in free solution. Here, we used CE LIF to study the free solution behavior of DNA-methyl-CpG-binding domain protein (MBD2b) complexes through exploring the relationship between the mobilities, charge, and mass of DNA-protein complexes. This method is based on the effective separation of free DNA and DNA-protein complexes because of their different electrophoretic mobility in a certain electric field. In order to avoid protein adsorption, a polyacrylamide-coated capillary was used. Based on the evaluation of the electrophoretic behavior of formed DNA-MBD2b complexes, we found that the values of (MU0 /MU)-1 were directly proportional to the charge-to mass ratios of formed complexes, where the MU0 and MU are the mobility of free DNA probe and DNA-protein complex, respectively. The models were further validated by the complex mobilities of protein with various lengths of DNA probes. The deviation of experimental and calculated charge-to-mass ratios of formed complexes from the theoretical data was less than 10%, suggesting that our models are useful to analyze the DNA-binding properties of the purified MBD2b protein and help to analyze other DNA-protein complexes. Additionally, this study enhances the understanding of the influence of the charge-to-mass ratios of formed DNA-protein complexes on their separation and electrophoretic behaviors. PMID- 26377304 TI - An eDNA assay for Irish Petromyzon marinus and Salmo trutta and field validation in running water. AB - This pilot study presents an environmental DNA (eDNA) assay for sea lamprey Petromyzon marinus and brown trout Salmo trutta, two species of economic and conservation importance in the Republic of Ireland. The results demonstrate the effectiveness of eDNA for assessing presence of low-abundance taxa (here, P. marinus) for environmental managers, and they highlight the potential for assessing relative abundance of rare or invasive freshwater species. PMID- 26377305 TI - Intraocular pressure reduction and neuroprotection conferred by bone marrow derived mesenchymal stem cells in an animal model of glaucoma. AB - INTRODUCTION: Glaucoma is a sight-threatening retinal neuropathy associated with elevated intraocular pressure (IOP) due to degeneration and fibrosis of the trabecular meshwork (TM). Glaucoma medications aim to reduce IOP without targeting the specific TM pathology, Bone-marrow mesenchymal stem cells (MSCs) are used today in various clinical studies. Here, we investigated the potential of MSCs therapy in an glaucoma-like ocular hypertension (OHT) model and decipher in vitro the effects of MSCs on primary human trabecular meshwork cells. METHODS: Ocular hypertension model was performed by cauterization of 3 episcleral veins (EVC) of Long-Evans male rat eyes. MSCs were isolated from rat bone marrow, amplified in vitro and tagged with quantum dot nanocrystals. Animals were distributed as 1) MSCs group receiving 5.10(5)cells/6MUl Minimum Essential Medium and 2) MEM group receiving 6MUl MEM (n = 10 each). Injections were performed into the anterior chamber of 20 days-hypertensive eyes and IOP was monitored twice a week for 4 weeks. At the end of experiment, cell distribution in the anterior segment was examined in confocal microscopy on flat mounted corneas. Moreover, we tested in vitro effects of MSCs conditioned medium (MSC-CM) on primary human trabecular meshwork cells (hTM cells) using Akt activation, myosin phosphorylation and TGF-beta2-dependent profibrotic phenotype in hTM cells. RESULTS: We demonstrated a rapid and long-lasting in vivo effect of MSCs transplantation that significantly reduced IOP in hypertensive eyes induced by EVC. MSCs were located to the ciliary processes and the TM. Enumeration of RGCs on whole flat-mounted retina highlighted a protective effect of MSCs on RGCs death. In vitro, MSC-CM promotes: (i) hTM cells survival by activating the antiapoptotic pathway, Akt, (ii) hTM cells relaxation as analyzed by the decrease in myosin phosphorylation and (iii) inhibition of TGF-beta2-dependent profibrotic phenotype acquisition in hTM cells. CONCLUSIONS: MSCs injection in the ocular anterior chamber in a rat model of OHT provides neuroprotective effect in the glaucoma pathophysiology via TM protection. These results demonstrate that MSCs constitute promising tool for treating ocular hypertension and retinal cell degeneration. PMID- 26377306 TI - A phase II study on the efficacy and safety of procedural analgesia with fentanyl buccal tablet in cancer patients for the placement of indwelling central venous access systems. AB - BACKGROUND: Pain in cancer patients is often related to oncologic therapies and diagnostic procedures. The placement of fully implantable venous access systems is a very common procedure in oncology patients. Local anaesthesia is the method most commonly used to overcome pain related to this surgical procedure, but the local anaesthetic may be unable to completely eradicate all pain. This study investigates the effectiveness and safety of fentanyl buccal tablet (FBT), administered by OraVescent(r) technology, in reducing procedural pain related to the placement of indwelling central venous access systems (Ports) in opioid-naive cancer patients. METHODS: Inpatients who required an indwelling vascular access (Port) were preoperatively assessed with a self-assessment questionnaire on anxiety and pain. A 100 MUg FBT was administered 10 min before preparation of the operating field. A self-assessment scale for pain experienced during the procedure was administered at the end of the procedure. Vital signs and the presence of any side effects or bothersome symptoms were monitored during the procedure, at the end, and 4 h later. RESULTS: From October 2012 to June 2014, 65 patients were enrolled in the study. A total of 61 (93.9 %) patients perceived no or a little pain during the procedure. Four patients (6.2 %) reported a lot of pain. No patient reported very severe pain. This data is significant in terms of the lower than expected presence of pain (Fisher test p = 0.0018) as assessed in our previous experience without procedural analgesia. The most common side effects of FBT was drowsiness, experienced by 28 patients at the end of the procedure (43.1 %), significantly reduced (p < 0.01) to 8 patients after 4 h (12.5 %). Nausea was present in 6 cases at the end of the procedure (9.2 %) and in 7 cases 4 h later (10.9 %). Vomiting was present in 3 cases at the end (4.7 %) and in 2 other patients after 4 h (7.8 %). No significant change of vital parameters was observed between the baseline and the subsequent measurements in all patients studied. CONCLUSIONS: The significant improvement in the number of patients experiencing little or no pain, accompanied by a lower number of non severe side effects, suggests that FBT is a valid, practical and safe method of procedural analgesia. It will be necessary to perform further studies, taking into account the need for standard antiemetic pre-medication to minimise the incidence of nausea and vomiting. PMID- 26377307 TI - The sum of all fears: conceptual challenges with measuring fear of cancer recurrence. AB - Fear of cancer recurrence (FCR) is increasingly recognised as a major concern for people with cancer once active treatment is completed. Several instruments have been designed to assess FCR; however, no gold standard has emerged. Many instruments conceptualise FCR as a multidimensional construct. However, this potentially conflates FCR as an outcome with its antecedents and consequences. This is problematic when an aggregate of distinct dimensions is calculated, as is commonly recommended. For example, the total score on the Fear of Cancer Recurrence Inventory is an aggregate of items from seven sub-scales: triggers, severity, psychological distress, coping strategies, functioning impairments, insight and reassurance. Similarly, the total score on the Fear of Progression Questionnaire is an aggregate of affective reaction, partnership/family, work and loss of autonomy. Arguably, the severity and affective reaction domains represent fear, and the other sub-scales represent related concepts, rather than "dimensions" of FCR. The total score represents a combination of concepts whose meaning is unclear. The same total score could be produced by patients with very different experiences, and patients with the same level of fear could have very different total scores. Therefore, we argue that although the level of FCR may be determined by a complex network of antecedents and modifiers and have variable consequences, FCR itself may be a simple concept, which can be assessed using a smaller number of items. Conceptual clarity in its research infancy should prevent FCR becoming a construct that is vaguely operationalised and interpreted. PMID- 26377308 TI - A novel prospective descriptive analysis of nausea and vomiting among patients receiving gastrointestinal radiation therapy. AB - PURPOSE: Nausea and vomiting are common side effects from radiotherapy that can interfere with gastrointestinal (GI) cancer patients' quality of life (QOL). This study described the subjective experience of patients with radiation-induced nausea and vomiting (RINV) and its relation to QOL. METHODS: Forty-eight patients treated with abdominal radiotherapy alone or with concomitant chemoradiotherapy were followed in a prospective study. All episodes of nausea, vomiting, and antiemetic use were recorded daily for the treatment period and the week following completion of therapy. QOL was assessed weekly using the Functional Living Index-Emesis QOL Tool (FLIE) and the EORTC QLQ-C30 core questionnaire (C30). RESULTS: In total, 351 episodes of nausea severity, duration, onset time, and 154 outcomes of vomiting onset times and contents were documented. The median nausea severity experienced per episode was 5 (on a scale from 1 to 10), and the most common durations of nausea were 30 min or less and constant nausea all day and night. The most common location of nausea was the abdomen. Longer nausea duration, great nausea severities, and the location of nausea experienced had significant adverse relationships to multiple QOL items on both the FLIE and the C30. In addition, the onset timing and number of vomiting episodes were related to the majority of all FLIE and QOL scores. CONCLUSION: Patient's subjective experiences of RINV directly correlated to the worsening of QOL outcomes. The identification and amelioration of these RINV experiences could improve QOL. PMID- 26377309 TI - Fermentation and alternative respiration compensate for NADH dehydrogenase deficiency in a prokaryotic model of DJ-1-associated Parkinsonism. AB - YajL is the closest prokaryotic homologue of Parkinson's disease-associated DJ-1, a protein of undefined function involved in the oxidative stress response. We reported recently that YajL and DJ-1 protect cells against oxidative stress induced protein aggregation by acting as covalent chaperones for the thiol proteome, including the NuoG subunit of NADH dehydrogenase 1, and that NADH dehydrogenase 1 activity is negligible in the yajL mutant. We report here that this mutant compensates for low NADH dehydrogenase activity by utilizing NADH independent alternative dehydrogenases, including pyruvate oxidase PoxB and d amino acid dehydrogenase DadA, and mixed acid aerobic fermentations characterized by acetate, lactate, succinate and ethanol excretion. The yajL mutant has a low adenylate energy charge favouring glycolytic flux, and a high NADH/NAD ratio favouring fermentations over pyruvate dehydrogenase and the Krebs cycle. DNA array analysis showed upregulation of genes involved in glycolytic and pentose phosphate pathways and alternative respiratory pathways. Moreover, the yajL mutant preferentially catabolized pyruvate-forming amino acids over Krebs cycle related amino acids, and thus the yajL mutant utilizes pyruvate-centred respiro fermentative metabolism to compensate for the NADH dehydrogenase 1 defect and constitutes an interesting model for studying eukaryotic respiratory complex I deficiencies, especially those associated with Alzheimer's and Parkinson's diseases. PMID- 26377310 TI - Relationship between visible branch arteries distal to the stenosis on magnetic resonance angiography and stroke recurrence in patients with severe middle cerebral artery trunk stenosis: a one-year follow up study. AB - BACKGROUND: To evaluate the relationship between the flow signal intensity of branch arteries distal to the stenosis on 3-dimensional (3D) time-of-flight (TOF) magnetic resonance angiography (MRA) and the risk of stroke recurrence in patients with severe middle cerebral artery (MCA) trunk stenosis. METHODS: We prospectively recruited 153 patients (mean age 62.9 +/- 13.0 years, 106 males) with a first ischemic stroke or transient ischemic attack caused by a severe MCA trunk stenosis (70 % to 99 %) confirmed by 3D TOF MRA and followed them for one year to determine the stroke recurrence. The MCA branch signal intensity distal to the site of stenosis on 3D TOF MRA was classified as either good (grade A) or poor [mild reduction (grade B) or severe reduction (grade C)] according to the extent to which the MCA could be visualized. The patients were divided into groups A (35), B (58), or C (60) based on the MRA grading of the MCA branch signal intensity distal to the site of stenosis. RESULTS: Poor MCA branch signal intensity was associated with internal border-zone infarction (p < 0.05). The risk of stroke recurrence in the ipsilateral MCA in the first year was 18.3 %. The 1-year cumulative incidence of recurrence was higher in the patients in group C (30 %) than in groups B (12.1 %) or A (8.6 %) (Log rank, p = 0.007). Multivariate analyses via Cox proportional hazard regression demonstrated that only a grade C classification of the signal intensity of the MCA branches was an independent predictor of stroke recurrence in the ipsilateral MCA (hazard ratio = 3.0, 95 % confidence interval = 1.3-7.4, p = 0.014). CONCLUSIONS: This study demonstrated that MCA branch signal intensity as assessed via 3D TOF MRA may be a useful and simple tool to stratify the risk of stroke recurrence in patients with severe MCA trunk stenosis. PMID- 26377312 TI - Effects of Preoperative Positive Cross-Match and HLA Mismatching on Early Acute Cellular Rejection and Graft Survival in Living Donor Liver Transplantation. AB - BACKGROUND We evaluated the effects of preoperative positive cross-match and HLA mismatching on early acute cellular rejection and graft survival in living donor liver transplantation (LDLT). MATERIAL AND METHODS We retrospectively reviewed data of 286 patients who underwent LDLT from 2008 to 2013. Cross-matching tests were performed by complement-dependent lymphocytotoxicity (CDC) and flow cytometry (FCX) methods. The CDC cross-matching test was performed using the National Institutes of Health (NIH) standard cross-match and antiglobulin (AHG) cross-match methods. RESULTS NIH, AHG, and FCX were positive in T-lymphocytes from 18 (6.3%), 21(7.3%), and 23 (8.0%) patients, respectively. T-CDC (T-NIH or T AHG) results were positive in 23 (8.0%) patients. CDC and FCX results were positive in B-lymphocytes from 18 (6.3%) and 35 (12.2%) patients. All positive cross-match results were significantly associated with acute cellular rejection. Only a positive T-CDC cross-match was significantly associated with decreased graft survival (P=0.035). In a multivariate analysis, a positive T-CDC cross match was the only independent risk factor with a decreased graft survival rate (P=0.041). An HLA mismatch was not associated with acute rejection (p=0.468 for HLA-A, p=0.644 for HLA-B, and p=0.811 for HLA-DR), graft survival (p=0.895 for HLA-A, p=0.580 for HLA-B, and p=0.969 for HLA-DR), and overall survival (p=0.862 for HLA-A, p=0.634 for HLA-B, and p=0.917 for DLA-DR). CONCLUSIONS Although a further prospective study with a larger cohort is required, it is not wise nor safe to perform LDLT in the setting of a positive T-CDC cross-match result. PMID- 26377311 TI - Potential mechanisms of attenuation for rifampicin-passaged strains of Flavobacterium psychrophilum. AB - BACKGROUND: Flavobacterium psychrophilum is the etiologic agent of bacterial coldwater disease in salmonids. Earlier research showed that a rifampicin passaged strain of F. psychrophilum (CSF 259-93B.17) caused no disease in rainbow trout (Oncorhynchus mykiss, Walbaum) while inducing a protective immune response against challenge with the virulent CSF 259-93 strain. We hypothesized that rifampicin passage leads to an accumulation of genomic mutations that, by chance, reduce virulence. To assess the pattern of phenotypic and genotypic changes associated with passage, we examined proteomic, LPS and single-nucleotide polymorphism (SNP) differences for two F. psychrophilum strains (CSF 259-93 and THC 02-90) that were passaged with and without rifampicin selection. RESULTS: Rifampicin resistance was conveyed by expected mutations in rpoB, although affecting different DNA bases depending on the strain. One rifampicin-passaged CSF 259-93 strain (CR) was attenuated (4 % mortality) in challenged fish, but only accumulated eight nonsynonymous SNPs compared to the parent strain. A CSF 259-93 strain passaged without rifampicin (CN) accumulated five nonsynonymous SNPs and was partially attenuated (28 % mortality) compared to the parent strain (54.5 % mortality). In contrast, there were no significant change in fish mortalities among THC 02-90 wild-type and passaged strains, despite numerous SNPs accumulated during passage with (n = 174) and without rifampicin (n = 126). While only three missense SNPs were associated with attenuation, a Ser492Phe rpoB mutation in the CR strain may contribute to further attenuation. All strains except CR retained a gliding motility phenotype. Few proteomic differences were observed by 2D SDS-PAGE and there were no apparent changes in LPS between strains. Comparative methylome analysis of two strains (CR and TR) identified no shared methylation motifs for these two strains. CONCLUSION: Multiple genomic changes arose during passage experiments with rifampicin selection pressure. Consistent with our hypothesis, unique strain-specific mutations were detected for the fully attenuated (CR), partially attenuated (CN) and another fully attenuated strain (B17). PMID- 26377313 TI - Microenvironment in metastasis: roadblocks and supportive niches. AB - In many cancers, malignant cells can spread from the primary tumor through blood circulation and initiate metastasis in secondary organs. Metastatic colonization may depend not only on inherent properties of cancer cells, but also on suitable microenvironments in distant sites. Increasing evidence suggests that the nature of the microenvironment may determine the fate of disseminated cancer cells, providing either hindrance or support for cancer cell propagation. This can result in strong selective pressure where the vast majority of cancer cells, invading a secondary organ, are either eliminated or maintained in a dormant state. The ability of cancer cells to fend off or circumvent anti-metastatic signals from the stroma and the capacity to manipulate the local microenvironment towards a supporting environment, a metastatic niche, may be essential for metastatic growth. The molecular interactions between cancer cells and the stroma are still enigmatic, but recent studies are beginning to reveal their nature. Here, we discuss the interactive relationship between metastatic cancer cells and host stroma, involving selection and adaptation of metastasis-initiating cells and host tissue remodeling. Understanding the dynamic and continuously evolving cross talk between metastatic cancer cells and the stroma may be crucial when developing cancer treatments. PMID- 26377314 TI - Dynamics of myosin replacement in skeletal muscle cells. AB - Highly organized thick filaments in skeletal muscle cells are formed from ~300 myosin molecules. Each thick-filament-associated myosin molecule is thought to be constantly exchanged. However, the mechanism of myosin replacement remains unclear, as does the source of myosin for substitution. Here, we investigated the dynamics of myosin exchange in the myofibrils of cultured myotubes by fluorescent recovery after photobleaching and found that myofibrillar myosin is actively replaced with an exchange half-life of ~3 h. Myosin replacement was not disrupted by the absence of the microtubule system or by actomyosin interactions, suggesting that known cytoskeletal systems are dispensable for myosin substitution. Intriguingly, myosin replacement was independent of myosin binding protein C, which links myosin molecules together to form thick filaments. This implies that an individual myosin molecule rather than a thick filament functions as an exchange unit. Furthermore, the myosin substitution rate was decreased by the inhibition of protein synthesis, suggesting that newly synthesized myosin, as well as preexisting cytosolic myosin, contributes to myosin replacement in myofibrils. Notably, incorporation and release of myosin occurred simultaneously in myofibrils, but rapid myosin release from myofibrils was observed without protein synthesis. Collectively, our results indicate that myosin shuttles between myofibrils and the nonmyofibrillar cytosol to maintain a dynamic equilibrium in skeletal muscle cells. PMID- 26377315 TI - O-GlcNAcylation of connexin 40: a sweet connection between diabetes and endothelial cell dysfunction? Focus on "O-GlcNAcase overexpression reverses coronary endothelial cell dysfunction in type 1 diabetic mice". PMID- 26377316 TI - The association of health literacy with adherence in older adults, and its role in interventions: a systematic meta-review. AB - BACKGROUND: Low health literacy is a common problem among older adults. It is often suggested to be associated with poor adherence. This suggested association implies a need for effective adherence interventions in low health literate people. However, previous reviews show mixed results on the association between low health literacy and poor adherence. A systematic meta-review of systematic reviews was conducted to study the association between health literacy and adherence in adults above the age of 50. Evidence for the effectiveness of adherence interventions among adults in this age group with low health literacy was also explored. METHODS: Eight electronic databases (MEDLINE, ERIC, EMBASE, PsycINFO, CINAHL, DARE, the Cochrane Library, and Web of Knowledge) were searched using a variety of keywords regarding health literacy and adherence. Additionally, references of identified articles were checked. Systematic reviews were included if they assessed the association between health literacy and adherence or evaluated the effectiveness of interventions to improve adherence in older adults with low health literacy. The AMSTAR tool was used to assess the quality of the included reviews. The selection procedure, data-extraction, and quality assessment were performed by two independent reviewers. Seventeen reviews were selected for inclusion. RESULTS: Reviews varied widely in quality. Both reviews of high and low quality found only weak or mixed associations between health literacy and adherence among older adults. Reviews report on seven studies that assess the effectiveness of adherence interventions among low health literate older adults. The results suggest that some adherence interventions are effective for this group. The interventions described in the reviews focused mainly on education and on lowering the health literacy demands of adherence instructions. No conclusions could be drawn about which type of intervention could be most beneficial for this population. CONCLUSIONS: Evidence on the association between health literacy and adherence in older adults is relatively weak. Adherence interventions are potentially effective for the vulnerable population of older adults with low levels of health literacy, but the evidence on this topic is limited. Further research is needed on the association between health literacy and general health behavior, and on the effectiveness of interventions. PMID- 26377317 TI - MALT1 is not alone after all: identification of novel paracaspases. AB - Paracaspases and metacaspases are two families of caspase-like proteins identified in 2000. Up until now paracaspases were considered a single gene family with one known non-metazoan paracaspase in the slime mold Dictyostelium and a single animal paracaspase called MALT1. Human MALT1 is a critical signaling component in many innate and adaptive immunity pathways that drive inflammation, and when it is overly active, it can also cause certain forms of cancer. Here, we report the identification and functional analysis of two new vertebrate paracaspases, PCASP2 and PCASP3. Functional characterization indicates that both scaffold and protease functions are conserved across the three vertebrate paralogs. This redundancy might explain the loss of two of the paralogs in mammals and one in Xenopus. Several of the vertebrate paracaspases currently have incorrect or ambiguous annotations. We propose to annotate them accordingly as PCASP1, PCASP2, and PCASP3 similar to the caspase gene nomenclature. A comprehensive search in other metazoans and in non-metazoan species identified additional new paracaspases. We also discovered the first animal metacaspase in the sponge Amphimedon. Comparative analysis of the active site suggests that paracaspases constitute one of the several subclasses of metacaspases that have evolved several times independently. PMID- 26377318 TI - The keepers of the ring: regulators of FtsZ assembly. AB - FtsZ, a GTPase distributed in the cytoplasm of most bacteria, is the major component of the machinery responsible for division (the divisome) in Escherichia coli. It interacts with additional proteins that contribute to its function forming a ring at the midcell that is essential to constrict the membrane. FtsZ is indirectly anchored to the membrane and it is prevented from polymerizing at locations where septation is undesired. Several properties of FtsZ are mediated by other proteins that function as keepers of the ring. ZipA and FtsA serve to anchor the ring, and together with a set of Zap proteins, they stabilize it. The MinCDE and SlmA proteins prevent the polymerization of FtsZ at sites other than the midcell. Finally, ClpP degrades FtsZ, an action prevented by ZipA. Many of the FtsZ keepers interact with FtsZ through a central hub located at its carboxy terminal end. PMID- 26377320 TI - Parenting around child snacking: development of a theoretically-guided, empirically informed conceptual model. AB - BACKGROUND: Snacking contributes to excessive energy intakes in children. Yet factors shaping child snacking are virtually unstudied. This study examines food parenting practices specific to child snacking among low-income caregivers. METHODS: Semi-structured interviews were conducted in English or Spanish with 60 low-income caregivers of preschool-aged children (18 non-Hispanic white, 22 African American/Black, 20 Hispanic; 92% mothers). A structured interview guide was used to solicit caregivers' definitions of snacking and strategies they use to decide what, when and how much snack their child eats. Interviews were audio recorded, transcribed verbatim and analyzed using an iterative theory-based and grounded approach. A conceptual model of food parenting specific to child snacking was developed to summarize the findings and inform future research. RESULTS: Caregivers' descriptions of food parenting practices specific to child snacking were consistent with previous models of food parenting developed based on expert opinion [1, 2]. A few noteworthy differences however emerged. More than half of participants mentioned permissive feeding approaches (e.g., my child is the boss when it comes to snacks). As a result, permissive feeding was included as a higher order feeding dimension in the resulting model. In addition, a number of novel feeding approaches specific to child snacking emerged including child centered provision of snacks (i.e., responding to a child's hunger cues when making decisions about snacks), parent unilateral decision making (i.e., making decisions about a child's snacks without any input from the child), and excessive monitoring of snacks (i.e., monitoring all snacks provided to and consumed by the child). The resulting conceptual model includes four higher order feeding dimensions including autonomy support, coercive control, structure and permissiveness and 20 sub-dimensions. CONCLUSIONS: This study formulates a language around food parenting practices specific to child snacking, identifies dominant constructs, and proposes a conceptual framework to guide future research. PMID- 26377319 TI - 'Medusa head ataxia': the expanding spectrum of Purkinje cell antibodies in autoimmune cerebellar ataxia. Part 3: Anti-Yo/CDR2, anti-Nb/AP3B2, PCA-2, anti Tr/DNER, other antibodies, diagnostic pitfalls, summary and outlook. AB - Serological testing for anti-neural autoantibodies is important in patients presenting with idiopathic cerebellar ataxia, since these autoantibodies may indicate cancer, determine treatment and predict prognosis. While some of them target nuclear antigens present in all or most CNS neurons (e.g. anti-Hu, anti Ri), others more specifically target antigens present in the cytoplasm or plasma membrane of Purkinje cells (PC). In this series of articles, we provide a detailed review of the clinical and paraclinical features, oncological, therapeutic and prognostic implications, pathogenetic relevance, and differential laboratory diagnosis of the 12 most common PC autoantibodies (often referred to as 'Medusa head antibodies' due to their characteristic somatodendritic binding pattern when tested by immunohistochemistry). To assist immunologists and neurologists in diagnosing these disorders, typical high-resolution immunohistochemical images of all 12 reactivities are presented, diagnostic pitfalls discussed and all currently available assays reviewed. Of note, most of these antibodies target antigens involved in the mGluR1/calcium pathway essential for PC function and survival. Many of the antigens also play a role in spinocerebellar ataxia. Part 1 focuses on anti-metabotropic glutamate receptor 1 , anti-Homer protein homolog 3-, anti-Sj/inositol 1,4,5-trisphosphate receptor- and anti-carbonic anhydrase-related protein VIII-associated autoimmune cerebellar ataxia (ACA); part 2 covers anti-protein kinase C gamma-, anti-glutamate receptor delta-2-, anti-Ca/RhoGTPase-activating protein 26- and anti-voltage-gated calcium channel-associated ACA; and part 3 reviews the current knowledge on anti-Tr/delta notch-like epidermal growth factor-related receptor-, anti-Nb/AP3B2-, anti Yo/cerebellar degeneration-related protein 2- and Purkinje cell antibody 2 associated ACA, discusses differential diagnostic aspects and provides a summary and outlook. PMID- 26377321 TI - Lactic acid bacteria: reviewing the potential of a promising delivery live vector for biomedical purposes. AB - Lactic acid bacteria (LAB) have a long history of safe exploitation by humans, being used for centuries in food production and preservation and as probiotic agents to promote human health. Interestingly, some species of these Gram positive bacteria, which are generally recognized as safe organisms by the US Food and Drug Administration (FDA), are able to survive through the gastrointestinal tract (GIT), being capable to reach and colonize the intestine, where they play an important role. Besides, during the last decades, an important effort has been done for the development of tools to use LAB as microbial cell factories for the production of proteins of interest. Given the need to develop effective strategies for the delivery of prophylactic and therapeutic molecules, LAB have appeared as an appealing option for the oral, intranasal and vaginal delivery of such molecules. So far, these genetically modified organisms have been successfully used as vehicles for delivering functional proteins to mucosal tissues in the treatment of many different pathologies including GIT related pathologies, diabetes, cancer and viral infections, among others. Interestingly, the administration of such microorganisms would suppose a significant decrease in the production cost of the treatments agents since being live organisms, such vectors would be able to autonomously amplify and produce and deliver the protein of interest. In this context, this review aims to provide an overview of the use of LAB engineered as a promising alternative as well as a safety delivery platform of recombinant proteins for the treatment of a wide range of diseases. PMID- 26377322 TI - The effect of massage therapy and/or exercise therapy on subacute or long-lasting neck pain--the Stockholm neck trial (STONE): study protocol for a randomized controlled trial. AB - BACKGROUND: Neck pain is a major health problem in populations worldwide and an economic burden in modern societies due to its high prevalence and costs in terms of health care expenditures and lost productivity. Massage and exercise therapy are widely used management options for neck pain. However, there is a lack of scientific evidence regarding their effectiveness for subacute and long-lasting neck pain. This study protocol describes a randomized controlled trial aiming to determine the effect of massage and/or exercise therapy on subacute and long lasting neck pain over the course of 1 year. METHODS/DESIGN: A randomized controlled trial in which at least 600 study participants with subacute or long lasting nonspecific neck pain will be recruited and randomly allocated to one of four treatment arms: massage therapy (A), exercise therapy (B), exercise therapy plus massage therapy (C) and advice to stay active (D). The study has an E-health approach, and study participants are being recruited through advertising with a mix of traditional and online marketing channels. Web-based self-report questionnaires measure the main outcomes at 7, 12, 26 and 52 weeks after inclusion. The primary outcomes are a clinically important improvement in pain intensity and pain-related disability at follow-up, measured with a modified version of the Chronic Pain Questionnaire (CPQ). The secondary outcomes are global improvement, health-related quality of life (EQ-5D), sick leave, drug consumption and healthcare utilization. Adverse events are measured by questionnaires at return visits to the clinic, and automated text messages (SMSes) survey neck pain intensity and pain-related disability every week over one year. DISCUSSION: The results of this study will provide clinicians and stakeholders much needed knowledge to plan medical care for subacute and long lasting neck pain disorders. TRIAL REGISTRATION: Current Controlled Trials ISRCTN01453590. Date of registration: 3 July 2014. PMID- 26377323 TI - EZH2 is a sensitive marker of malignancy in salivary gland tumors. AB - BACKGROUND: The immunohistochemical detection of Enhancer of zeste homologue 2 (EZH2) proved to be a useful tool to recognize the malignant nature of tumors in a wide variety of neoplasms. The histological diagnostics of salivary gland tumors is a challenging task, and a reliable marker of malignancy would be extremely helpful. METHODS: EZH2 expression was investigated in 54 malignant and 40 benign salivary gland tumors of various histological types by standard immunohistochemistry. RESULTS: The majority (n = 52) of the malignant tumors stained positively, while all the investigated benign tumors were negative for EZH2. CONCLUSIONS: EZH2 expression in salivary gland tumors, similarly to the tumors of other organs is not characteristic for any tumor type, but is a solid marker of the malignant nature of the tumors. PMID- 26377324 TI - Spinal plasticity in robot-mediated therapy for the lower limbs. AB - Robot-mediated therapy can help improve walking ability in patients following injuries to the central nervous system. However, the efficacy of this treatment varies between patients, and evidence for the mechanisms underlying functional improvements in humans is poor, particularly in terms of neural changes in the spinal cord. Here, we review the recent literature on spinal plasticity induced by robotic-based training in humans and propose recommendations for the measurement of spinal plasticity using robotic devices. Evidence for spinal plasticity in humans following robotic training is limited to the lower limbs. Body weight-supported (BWS) robotic-assisted step training of patients with spinal cord injury (SCI) or stroke patients has been shown to lead to changes in the amplitude and phase modulation of spinal reflex pathways elicited by electrical stimulation or joint rotations. Of particular importance is the finding that, among other changes to the spinal reflex circuitries, BWS robotic assisted step training in SCI patients resulted in the re-emergence of a physiological phase modulation of the soleus H-reflex during walking. Stretch reflexes elicited by joint rotations constitute a tool of interest to probe spinal circuitry since the technology necessary to produce these perturbations could be integrated as a natural part of robotic devices. Presently, ad-hoc devices with an actuator capable of producing perturbations powerful enough to elicit the reflex are available but are not part of robotic devices used for training purposes. A further development of robotic devices that include the technology to elicit stretch reflexes would allow for the spinal circuitry to be routinely tested as a part of the training and evaluation protocols. PMID- 26377325 TI - Green chemicals from pulp production black liquor by partial wet oxidation. AB - To reduce greenhouse gas emissions, more sustainable sources of energy, fuel and chemicals are needed. Biomass side streams such as black liquor, which is a by product of pulp production, has the potential to be used for this purpose. The aim of the study was the production of carboxylic acids, such as lactic acid, formic acid and acetic acid, from kraft and non-wood black liquor. The processes studied were partial wet oxidation (PWO) and catalytic partial wet oxidation (CPWO). The results show that the yield of carboxylic acid is higher when treated by PWO than the results from CPWO at temperatures of 170 degrees C and 230 degrees C. The results shows that the PWO process can increase the yield of carboxylic acids and hydroxy acids in black liquor, reduce lignin content and decrease pH, which makes further separation of the acids more favourable. The hydroxy acids are valuable raw materials for biopolymers, and acetic acid and formic acid are commonly used chemicals conventionally produced from fossil feedstock. PMID- 26377326 TI - Postoperative external beam irradiation with and without brachytherapy in pelvic node-positive IB1-IIA2 cervical cancer patients: a retrospective clinical study. AB - BACKGROUND: This study assessed the survival outcomes and recurrent patterns in pelvic node-positive IB1-IIA2 cervical cancer patients treated with postoperative external beam irradiation with or without vaginal brachytherapy. METHODS: The records of 1149 cervical cancer patients received radical surgery between February 2008 and March 2010 were retrospectively reviewed. 126 stages IB1-IIA2 patients with positive pelvic lymph node (LN) were included and a total of 113 patients who received different postoperative radiation therapy were identified and analyzed. Of the enrolled patients, 55 patients received pelvic external beam radiotherapy (EBRT) without vaginal brachytherapy and 58 patients received pelvic EBRT with vaginal brachytherapy. Treatment-related toxicities were evaluated. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier estimates and statistical significance was determined using the log rank test. RESULTS: With a median follow-up of 47 months (range: 10-61 months), the group which had pelvic EBRT with brachytherapy had a significantly improved 5 year PFS rate (P = 0.044), but no significant difference in 5-year overall survival was found between the two groups (P = 0.437). In patients treated without brachytherapy, the most common site of relapse was the pelvis. No significant differences were found regards to acute and chronic radiation toxicities, including myelosuppression, dermatitis, enterocolitis, proctitis and cystitis (P = 0.485, 0.875, 0.671, 0.459 and 0.969 respectively) between the groups of pelvic EBRT with and without vaginal brachytherapy. CONCLUSIONS: Treated with pelvic EBRT in combination with vaginal brachytherapy, cervical cancer patients with positive pelvic lymph node had a reduced risk of locoregional recurrence without increased side effects compared with patients treated with pelvic EBRT without vaginal brachytherapy. PMID- 26377328 TI - The Person and the Partner: Individual Differences Moderate the Relationship Between Partner Feedback and Condom Use. AB - Attachment anxiety is negatively associated with condom use; however, little research has assessed mechanisms underlying this relationship. In two studies we assessed the relationships among attachment orientations, perceived partner rejection, and condom use. In Study 1 we used a survey methodology and found that a measure of perceived partner rejection mediated the relationship between attachment anxiety and reported condom use behavior. In Study 2, women responded to condom use scenarios in which rejection was manipulated. We found a three-way interaction among attachment anxiety, attachment avoidance, and condom use intentions, such that perceived rejection from a potential sexual partner was associated with greater intentions to engage in unprotected sexual intercourse among women high in attachment anxiety and low in attachment avoidance, and among those high in attachment avoidance and low in attachment anxiety. PMID- 26377327 TI - A longitudinal analysis of diet quality scores and the risk of incident depression in the SUN Project. AB - BACKGROUND: Some studies have pointed out that several dietary patterns could be associated with a reduced risk of depression among adults. This association seems to be consistent across countries, cultures and populations. The objective of the study was to compare and to establish the type of relationship between three diet quality scores and depression in the SUN (Seguimiento Universidad de Navarra) Cohort study. METHODS: We performed a dynamic cohort study based on Spanish university graduates free of depression at baseline. Dietary intake was repeatedly assessed at baseline and after 10 years of follow-up with a validated semi-quantitative food-frequency questionnaire. Three previously described diet quality scores: Mediterranean Diet Score (MDS), Pro-vegetarian Dietary Pattern (PDP) and Alternative Healthy Eating Index-2010 (AHEI-2010) were built. Participants were classified as having depression if they reported a new clinical diagnosis of depression by a physician or initiated the use of an antidepressant drug during follow-up. Time-dependent Cox regression models with cumulative averages of diet and restricted cubic splines were used to estimate hazard ratios of depression according to quintiles of adherence to the MDS, PDP and AHEI-2010. RESULTS: One thousand and fifty one incident cases of depression were observed among 15,093 participants from the SUN Cohort after a median follow-up of 8.5 years. Inverse and significant associations were observed between the three diet quality scores and depression risk. The hazard ratios and 95 % confidence intervals for extreme quintiles (fifth versus first) of updated adherence to MDS, PDP and AHEI-2010 were 0.84 (0.69-1.02), 0.74 (0.61-0.89) and 0.60 (0.49-0.72), respectively. The dose-response analyses showed non-linear associations, suggesting that suboptimal adherence to these dietary patterns may partially be responsible for increased depression risk. CONCLUSIONS: Better adherence to the MDS, PDP and AHEI-2010 was associated with a reduced risk of depression among Spanish adults. However, our data suggested a threshold effect so that although the risk of depression was reduced when comparing moderate versus lower adherence, there was not much extra benefit for the comparison between moderate and high or very high adherence. PMID- 26377331 TI - Androgen levels and apoptosis in the testis during postnatal development of finasteride-treated male rat offspring. AB - INTRODUCTION: The hormone-dependent events that occur throughout the first wave of spermatogenesis, such as the establishment of the number of Sertoli cells (SCs) and spermatogonial stem cells (SSCs) within the seminiferous cords and the setting up of the blood-testis barrier, are important for adult male fertility. Any changes in the T/DHT ratio can result in male subfertility or even infertility. In this study we aimed to evaluate effects of paternal exposure to 5 alpha reductase type 2 inhibitor, finasteride on litter size, androgen levels and germ cell apoptosis in male offspring during postnatal development. MATERIAL AND METHODS: The subjects of the study were 7, 14, 21/22, 28, and 90-day-old Wistar male rats (F1:Fin) born from females fertilized by finasteride-treated rats. Offspring born from untreated parental animals were used as a control group (F1:Control). Animals and the collected testes were weighed, blood and intratesticular levels of T and DHT were measured by ELISA, and the apoptotic index of testicular cells was evaluated by TUNEL technique. RESULTS: We observed difficulties in obtaining male newborns from female rats fertilized by finasteride-treated male rats. In the F1:Fin rats, changes in the body and testes weights occurred, and a lower number of apoptotic cells was found during postnatal maturation of the seminiferous epithelium. Changes in androgen concentrations during the first spermatogenesis wave and adult life were also evident. CONCLUSION: Finasteride treatment of male adult rats may not only cause a decrease in the fertility of parental rats, but also could lead to incorrect, androgen-sensitive course of spermatogenesis in their offspring. PMID- 26377330 TI - Aerobic exercise training enhances the in vivo cholesterol trafficking from macrophages to the liver independently of changes in the expression of genes involved in lipid flux in macrophages and aorta. AB - BACKGROUND: Regular exercise prevents and regresses atherosclerosis by improving lipid metabolism and antioxidant defenses. Exercise ameliorates the reverse cholesterol transport (RCT), an antiatherogenic system that drives cholesterol from arterial macrophages to the liver for excretion into bile and feces. In this study we analyzed the role of aerobic exercise on the in vivo RCT and expression of genes and proteins involved in lipid flux and inflammation in peritoneal macrophages, aortic arch and liver from wild type mice. METHODS: Twelve-week-old male mice were divided into sedentary and trained groups. Exercise training was performed in a treadmill (15 m/min, 30 min/day, 5 days/week). Plasma lipids were determined by enzymatic methods and lipoprotein profile by fast protein liquid chromatography. After intraperitoneal injection of J774-macrophages the RCT was assessed by measuring the recovery of (3)H-cholesterol in plasma, feces and liver. The expression of liver receptors was determined by immunoblot, macrophages and aortic mRNAs by qRT-PCR. (14)C-cholesterol efflux mediated by apo A-I and HDL2 and the uptake of (3)H-cholesteryl oleoyl ether ((3)H-COE) acetylated-LDL were determined in macrophages isolated from sedentary and trained animals 48 h after the last exercise session. RESULTS: Body weight, plasma lipids, lipoprotein profile, glucose and blood pressure were not modified by exercise training. A greater amount of (3)H-cholesterol was recovered in plasma (24 h and 48 h) and liver (48 h) from trained animals in comparison to sedentary. No difference was found in (3)H-cholesterol excreted in feces between trained and sedentary mice. The hepatic expression of scavenger receptor class B type I (SR BI) and LDL receptor (B-E) was enhanced by exercise. We observed 2.8 and 1.7 fold rise, respectively, in LXR and Cyp7a mRNA in the liver of trained as compared to sedentary mice. Macrophage and aortic expression of genes involved in lipid efflux was not systematically changed by physical exercise. In agreement, (14)C cholesterol efflux and uptake of (3)H-COE-acetylated-LDL by macrophages was similar between sedentary and trained animals. CONCLUSION: Aerobic exercise in vivo accelerates the traffic of cholesterol from macrophages to the liver contributing to prevention and regression of atherosclerosis, independently of changes in macrophage and aorta gene expression. PMID- 26377329 TI - Absence of association between Plasmodium falciparum small sub-unit ribosomal RNA gene mutations and in vitro decreased susceptibility to doxycycline. AB - BACKGROUND: Doxycycline is an antibiotic used in combination with quinine or artesunate for malaria treatment or alone for malaria chemoprophylaxis. Recently, one prophylactic failure has been reported, and several studies have highlighted in vitro doxycycline decreased susceptibility in Plasmodium falciparum isolates from different areas. The genetic markers that contribute to detecting and monitoring the susceptibility of P. falciparum to doxycycline, the pfmdt and pftetQ genes, have recently been identified. However, these markers are not sufficient to explain in vitro decreased susceptibility of P. falciparum to doxycycline. In this paper, the association between polymorphism of the small sub unit ribosomal RNA apicoplastic gene pfssrRNA (PFC10_API0057) and in vitro susceptibilities of P. falciparum isolates to doxycycline were investigated. METHODS: Doxycycline IC50 determinations using the hypoxanthine uptake inhibition assay were performed on 178 African and Thai P. falciparum isolates. The polymorphism of pfssrRNA was investigated in these samples by standard PCR followed by sequencing. RESULTS: No point mutations were found in pfssrRNA in the Thai or African isolates, regardless of the determined IC50 values. CONCLUSIONS: The pfssrRNA gene is not associated with in vitro decreased susceptibility of P. falciparum to doxycycline. Identifying new in vitro molecular markers associated with reduced susceptibility is needed, to survey the emergence of doxycycline resistance. PMID- 26377332 TI - Effects of pelvic organ prolapse ring pessary therapy on intravaginal microbial flora. AB - INTRODUCTION AND HYPOTHESIS: The purpose of this paper is to report our evaluation of changes in intravaginal microbial flora after ring pessary therapy for pelvic organ prolapse (POP) using conventional and our clone library method. METHODS: Thirteen patients with POP who were fitted with a ring pessary participated in this longitudinal study that incorporates data from before and 1 month after beginning ring pessary therapy. Changes in intravaginal microbial flora were evaluated by conventional methods, i.e., vaginal pH, lactobacillary grade (LAC grade), Nugent score, and culture-based bacterial detection methods. In addition, we performed our clone library method using 16S ribosomal RNA (rRNA) sequencing of vaginal fluid. RESULTS: Conventional methods revealed that most patients had abnormal intravaginal microbial flora. Mean numbers of detected bacterial species by the culture-based and our clone library method were 3.1 (1 6) and 11.8 (1-25), respectively. Our clone library method showed that Lactobacillus spp. increased in four and decreased in two cases after ring pessary therapy but reappeared after therapy in two cases; no Lactobacillus spp. were detected in five cases. CONCLUSIONS: Our study showed that ring pessary therapy did not always disturb intravaginal microbial flora, especially for patients with Lactobacillus spp. prior to ring pessary insertion. Anaerobic circumstances in the vagina after therapy seem to have induced the growth of anaerobic bacteria. PMID- 26377333 TI - Recommendations for Use and Fit-for-Purpose Validation of Biomarker Multiplex Ligand Binding Assays in Drug Development. AB - Multiplex ligand binding assays (LBAs) are increasingly being used to support many stages of drug development. The complexity of multiplex assays creates many unique challenges in comparison to single-plexed assays leading to various adjustments for validation and potentially during sample analysis to accommodate all of the analytes being measured. This often requires a compromise in decision making with respect to choosing final assay conditions and acceptance criteria of some key assay parameters, depending on the intended use of the assay. The critical parameters that are impacted due to the added challenges associated with multiplexing include the minimum required dilution (MRD), quality control samples that span the range of all analytes being measured, quantitative ranges which can be compromised for certain targets, achieving parallelism for all analytes of interest, cross-talk across assays, freeze-thaw stability across analytes, among many others. Thus, these challenges also increase the complexity of validating the performance of the assay for its intended use. This paper describes the challenges encountered with multiplex LBAs, discusses the underlying causes, and provides solutions to help overcome these challenges. Finally, we provide recommendations on how to perform a fit-for-purpose-based validation, emphasizing issues that are unique to multiplex kit assays. PMID- 26377335 TI - Combined effect of ultrasound and essential oils to reduce Listeria monocytogenes on fresh produce. AB - Salads prepared from contaminated fresh produce have a high risk of causing food borne illnesses. Essential oils obtained from plants have antimicrobial activity and may provide a natural approach to reduce the pathogens on fresh produce. Additionally, ultrasound treatments have been shown to reduce the microbial counts on different foods. The objective of this study was to investigate the antimicrobial activities of cinnamon and lemon essential oils in vitro and in food applications. Mixtures of lettuce, parsley and dill were inoculated with Listeria monocytogenes and then dip-treated for 5 min in one of the following treatments: sterile tap water, chlorinated water, 1% lemon essential oil, 2% cinnamon essential oil or 2% cinnamon essential oil + ultrasound. The samples were stored at 4 C and collected at d 0, 1, 3, 5, 7 and 9 post inoculation. The 1% lemon (4 log) and 2% cinnamon (2 log) essential oil washes provided partial inhibition against L. monocytogenes by d 1. The combined application of 2% cinnamon oil and ultrasound resulted in only 0.85 log inhibition by d 1; however, the number of L. monocytogenes increased during storage and became nearly equal to the control at d 9. Therefore, different combinations of essential oils with other antimicrobials or novel technologies are required. PMID- 26377334 TI - The Web-Surf Task: A translational model of human decision-making. AB - Animal models of decision-making are some of the most highly regarded psychological process models; however, there remains a disconnection between how these models are used for pre-clinical applications and the resulting treatment outcomes. This may be due to untested assumptions that different species recruit the same neural or psychological mechanisms. We propose a novel human foraging paradigm (Web-Surf Task) that we translated from a rat foraging paradigm (Restaurant Row) to evaluate cross-species decision-making similarities. We examined behavioral parallels in human and non-human animals using the respective tasks. We also compared two variants of the human task, one using videos and the other using photos as rewards, by correlating revealed and stated preferences. We demonstrate similarities in choice behaviors and decision reaction times in human and rat subjects. Findings also indicate that videos yielded more reliable and valid results. The joint use of the Web-Surf Task and Restaurant Row is therefore a promising approach for functional translational research, aiming to bridge pre clinical and clinical lines of research using analogous tasks. PMID- 26377337 TI - How to read a funnel plot in a meta-analysis. PMID- 26377336 TI - The efficacy of "AboundTM," a nutritional supplement containing L-glutamine, L arginine, citric acid, and calcium HMB, for skin disorders that developed as adverse drug reactions to anti-EGFR antibody preparation administration: pilot study. PMID- 26377338 TI - Modality-specific effects on crosstalk in task switching: evidence from modality compatibility using bimodal stimulation. AB - The present study was aimed at examining modality-specific influences in task switching. To this end, participants switched either between modality compatible tasks (auditory-vocal and visual-manual) or incompatible spatial discrimination tasks (auditory-manual and visual-vocal). In addition, auditory and visual stimuli were presented simultaneously (i.e., bimodally) in each trial, so that selective attention was required to process the task-relevant stimulus. The inclusion of bimodal stimuli enabled us to assess congruence effects as a converging measure of increased between-task interference. The tasks followed a pre-instructed sequence of double alternations (AABB), so that no explicit task cues were required. The results show that switching between two modality incompatible tasks increases both switch costs and congruence effects compared to switching between two modality compatible tasks. The finding of increased congruence effects in modality incompatible tasks supports our explanation in terms of ideomotor "backward" linkages between anticipated response effects and the stimuli that called for this response in the first place. According to this generalized ideomotor idea, the modality match between response effects and stimuli would prime selection of a response in the compatible modality. This priming would cause increased difficulties to ignore the competing stimulus and hence increases the congruence effect. Moreover, performance would be hindered when switching between modality incompatible tasks and facilitated when switching between modality compatible tasks. PMID- 26377339 TI - Single origin of the Mascarene stick insects: ancient radiation on sunken islands? AB - BACKGROUND: The study of islands as model systems plays a key role in understanding many evolutionary processes. Knowledge of the historical events leading to present-day island communities is pivotal for exploring fundamental mechanisms of speciation and adaptation. The remote Mascarene archipelago (Mauritius, Reunion, Rodrigues), considered to be the product of an age progressive trend of north-to-south volcanic activity in the Indian Ocean, hosts a remarkably diverse, endemic and threatened concentration of flora and fauna that has traditionally been considered to be biogeographically related to Madagascar and Africa. To explore the evolutionary diversity of the Mascarene stick insects (Phasmatodea), we constructed a global phylogeny from approximately 2.4 kb of mitochondrial and nuclear sequence data of more than 120 species representing all major phasmatodean lineages. RESULTS: Based on the obtained time calibrated molecular tree we demonstrate that the current phasmid community of the Mascarene archipelago, which consists of members of four presumably unrelated traditional subfamilies, is the result of a single ancient dispersal event from Australasia and started radiating between 16-29 million years ago, significantly predating the age of Mauritius (8-10 million years). CONCLUSIONS: We propose that the Mascarene stick insects diversified on landmasses now eroded away, presumably to the north of Mauritius. In consequence, ancient islands have probably persisted in the Indian Ocean until the emergence of Mauritius and not only served as stepping stones for colonisation events during sea-level lowstands, but as long-lasting cradles of evolution. These ancient landmasses most likely allowed for adaptive speciation and served as significant sources of diversity that contributed to the biomes of the Mascarene archipelago and the megadiverse Madagascar. PMID- 26377340 TI - Gastric Bypass-Related Effects on Glucose Control, beta Cell Function and Morphology in the Obese Zucker Rat. AB - BACKGROUND: Roux-en-Y gastric bypass (RYGB) may improve beta cell function by mechanisms other than caloric restriction and body weight loss. We aimed to assess the impact of anatomical and hormonal alterations specific to RYGB on glucose homeostasis, beta cell function and morphology. METHODS: Male Zucker(fa/fa) rats underwent either RYGB (n = 11) or sham surgeries (n = 10). Five of the shams were then food restricted and body weight matched (BWM) to the RYGB rats. Six male Zucker(fa/+) rats underwent sham surgery and served as additional lean controls. Twenty-seven days after surgery, an oral glucose tolerance test (OGTT) was performed and plasma levels of glucose, insulin and glucagon-like peptide-1 (GLP-1) were measured. Immunohistological analysis of pancreatic islets was performed, and GLP-1 receptor and PDX-1 mRNA content were quantified. RESULTS: Shams consumed more food and gained more weight compared to both RYGB and BWM (p < 0.001). Hyperglycaemia was evident in ad libitum-fed shams, whilst postprandial glucose levels were lower in RYGB compared to the BWM sham group (p < 0.05). During the OGTT, RYGB rats responded with >2.5-fold increase of GLP-1. Histology revealed signs of islet degeneration in ad libitum fed shams, but not in RYGB and sham BWM controls (p < 0.001). GLP-1 receptor and PDX-1 mRNA content was similar between the RYGB and BWM shams but higher compared to ad libitum shams (p < 0.05). CONCLUSIONS: Combined molecular, cellular and histological analyses of pancreatic function suggest that weight loss alone, and not the enhancement of GLP-1 responses, is predominant for the short-term beta cell protective effects of RYGB. PMID- 26377341 TI - A fast-responsive fluorescent probe for sulfite and its bioimaging. AB - A turn-on fluorescent probe Coumarin-SO2 based on a nucleophilic addition reaction was developed for the rapid detection of SO3(2-) in aqueous media. The probe Coumarin-SO2 displays excellent water solubility, fast response, highly sensitivity and highly selectivity over other biological related species. More importantly, living cell imaging experiments indicate the feasibility of using the probe for the detection of SO3(2-) in biological systems. PMID- 26377342 TI - Efficacy and safety of ivabradine in patients with chronic systolic heart failure and diabetes: an analysis from the SHIFT trial. AB - AIMS: To evaluate clinical profiles and outcomes in patients with systolic heart failure (HF) with or without diabetes, and the efficacy and safety of ivabradine (heart rate-lowering agent) with respect to diabetic status. METHODS AND RESULTS: This is a post hoc analysis on patients in SHIFT, a randomized controlled trial in adults in sinus rhythm with systolic HF, left ventricular ejection fraction <=35%, and resting heart rate >=70 b.p.m. Patients were randomized to ivabradine (titrated to 7.5 mg bid) or placebo. Diabetic status was established by medical history at baseline. The primary composite endpoint (PCE) was cardiovascular death or hospitalisation for worsening HF. Of 6505 patients, 30% had diabetes, 32% of whom used insulin. The PCE was more frequent in patients with diabetes [adjusted hazard ratio (HR) 1.18, 95% confidence interval (CI) 1.07-1.31; p = 0.001], as was hospitalization for worsening HF (adjusted HR 1.28, 95% CI 1.13 1.44; P < 0.001), and was increased in patients treated with insulin (adjusted HR 1.43, 95% CI 1.23-1.66; P < 0.01 vs. non-diabetics). Ivabradine significantly reduced the PCE in patients with and without diabetes (adjusted HR 0.80, 95% CI 0.68-0.94 and HR 0.84, 95% CI, 0.75-0.95, respectively; interaction P was non significant) vs. placebo. Adverse events were significantly more frequent in patients with diabetes (78%) than without (74%) (P < 0.001). Regardless of diabetic status, the incidence of serious adverse events was not significantly different between ivabradine and placebo. CONCLUSIONS: Comorbid diabetes in chronic HF worsens the prognosis of systolic HF patients. Irrespective of diabetic status, ivabradine is effective and safe in these patients. PMID- 26377344 TI - Cre-Mediated Recombination in Tas2r131 Cells-A Unique Way to Explore Bitter Taste Receptor Function Inside and Outside of the Taste System. AB - The type 2 taste receptors (Tas2rs) comprise a large family of G protein-coupled receptors that recognize compounds bitter to humans and aversive to vertebrates. Tas2rs are expressed in both gustatory and nongustatory tissues, however, identification and functional analyses of T2R-expressing cells have been difficult in most tissues. To overcome these limitations and to be able to manipulate Tas2r-expressing cells in vivo, we used gene-targeting to generate a Tas2r131-specific Cre knock-in mouse strain. We then employed a binary genetic approach to characterize Cre-mediated recombination in these animals and to investigate Tas2r131 expression during postnatal development. We demonstrate that a Cre-activated fluorescent reporter reliably visualizes Tas2r131-cells in gustatory tissue. We show that the onset of Tas2r131 as well as of alpha Gustducin expression is initiated at different developmental stages depending on the type of taste bud. Furthermore, the number of Tas2r131- and alpha-Gustducin expressing cells increased during postnatal development. Our results demonstrate that the Tas2r131-expressing cells constitute a subpopulation of alpha-Gustducin positive cells at all stages. We detected Tas2r131-expressing cells in several nongustatory tissues including lung, trachea, ovary, ganglia, and brain. Thus, the Tas2r131-Cre strain will help to dissect the functional role of Tas2r131 cells in both gustatory and nongustatory tissues in the future. PMID- 26377343 TI - Mitochondria and carbon monoxide: cytoprotection and control of cell metabolism - a role for Ca(2+) ? AB - Carbon monoxide (CO) is an endogenously produced gasotransmitter with important biological functions: anti-inflammation, anti-apoptosis, vasomodulation and cell metabolism modulation. The most recognized cellular target for CO is the mitochondria. Physiological concentrations of CO generate mitochondrial reactive oxygen species (ROS), which are signalling molecules for CO-induced pathways. Indeed, small amounts of ROS promote cytoprotection by a preconditioning effect. Furthermore, CO prevents cell death by limiting mitochondrial membrane permeabilization, which inhibits the release of pro-apoptotic factors into the cytosol; both events are ROS dependent. CO also increases the ability of mitochondria to take up Ca(2+) . Mitochondrial metabolism is modulated by CO, namely by increasing TCA cycle rate, oxidative phosphorylation and mitochondrial biogenesis, which, in turn, increases ATP production. CO's modulation of metabolism might be important for cellular response to diseases, namely cancer and ischaemic diseases. Finally, another cytoprotective role of CO involves the control of Ca(2+) channels. By limiting the activity of T-type and L-type Ca(2+) channels, CO prevents excitotoxicity-induced cell death and modulates cell proliferation. Several questions concerning Ca(2+) signalling, mitochondria and CO can be asked, for instance whether CO modulation of cell metabolism would be dependent on the mitochondrial Ca(2+) uptake capacity, since small amounts of Ca(2+) can increase mitochondrial metabolism. Whether CO controls Ca(2+) communication between mitochondria and endoplasmic reticulum is another open field of research. In summary, CO emerges as a key gasotransmitter in the control of several cellular functions of mitochondria: metabolism, cell death and Ca(2+) signalling. PMID- 26377345 TI - Identification of Odorant Binding Proteins and Chemosensory Proteins in Antennal Transcriptomes of the Jumping Bristletail Lepismachilis y-signata and the Firebrat Thermobia domestica: Evidence for an Independent OBP-OR Origin. AB - Chemosensory protein (CSP) and gustatory receptor genes have been identified in all major arthropod groups. However, odorant binding proteins (OBP) and olfactory receptor genes are insect specific, suggesting that both gene families originated after the Hexapoda-Crustacea split (~470 million years ago). The seemingly parallel diversification of OBP and olfactory receptors has been suggested as coevolution between these genes after insect terrestrialization. To test this hypothesis we used the recently published transcriptomes of the jumping bristletail Lepismachilis y-signata and the firebrat Thermobia domestica to search for putative OBP and CSP sequences and analyzed their relationship to binding proteins of other insects and crustaceans. Our results suggest an evolution and expansion of OBPs as an adaptation to a terrestrial insect lifestyle, independently from the emergence of olfactory receptors. PMID- 26377346 TI - Female Mice Avoid Male Odor from the Same Strain via the Vomeronasal System in an Estrogen-Dependent Manner. AB - Inbreeding avoidance is essential to providing offspring with genetic diversity. Females' mate choice is more crucial than males' for successful reproduction because of the high cost of producing gametes and limited chances to mate. However, the mechanism of female inbreeding avoidance is still unclear. To elucidate the mechanism underlying inbreeding avoidance by females, we conducted Y-maze behavioral assays using BALB/c and C57BL/6 female mice. In both strains, the avoidance of male urine from the same strain was lower in the low estrogen phase than in the high estrogen phase. The estrous cycle-dependent avoidance was completely prevented by vomeronasal organ (VNO) removal. To assess the regulation of the vomeronasal system by estrogen, the neural excitability was evaluated by immunohistochemistry of the immediate early gene products. Although estrogen did not affect neural excitability in the VNO, estrogen enhanced the neural excitability of the mitral cell layer in the AOB induced by urine from the cognate males. These results suggest that female mice avoid odor from genetically similar males in an estrogen-dependent manner via the vomeronasal system and the excitability of the mitral cells in the AOB is presumed to be regulated by estrogen. PMID- 26377347 TI - Extracting local surface charges and charge regulation behavior from atomic force microscopy measurements at heterogeneous solid-electrolyte interfaces. AB - We present a method to determine the local surface charge of solid-liquid interfaces from Atomic Force Microscopy (AFM) measurements that takes into account shifts of the adsorption/desorption equilibria of protons and ions as the cantilever tip approaches the sample. We recorded AFM force distance curves in dynamic mode with sharp tips on heterogeneous silica surfaces partially covered by gibbsite nano-particles immersed in an aqueous electrolyte with variable concentrations of dissolved NaCl and KCl at pH 5.8. Forces are analyzed in the framework of Derjaguin-Landau-Verwey-Overbeek (DLVO) theory in combination with a charge regulation boundary that describes adsorption and desorption reactions of protons and ions. A systematic method to extract the equilibrium constants of these reactions by simultaneous least-squared fitting to experimental data for various salt concentrations is developed and is shown to yield highly consistent results for silica-electrolyte interfaces. For gibbsite-electrolyte interfaces, the surface charge can be determined, yet, an unambiguous identification of the relevant surface speciation reactions is not possible, presumably due to a combination of intrinsic chemical complexity and heterogeneity of the nano particle surfaces. PMID- 26377348 TI - Perceived Control Mediates the Relations between Depressive Symptoms and Academic Achievement in Adolescence. AB - The present research examined the protective role played by perceived control in the relation between depressive symptoms and academic achievement in adolescence. A sample of 218 adolescents aged 11 to 16 filled in questionnaires to assess self reported depressive symptoms and three factors tied with Perceived Control (PC): self-regulated learning strategies use, effort attribution, and perceived competence. Grade Point Average (GPA) was considered as a measure of academic achievement. A path model showed that the relation between GPA and depressive symptoms is mediated by PC (p<.05), and became non-significant when PC is considered. The discussion stresses the need to take into account the strategic and motivational factors favouring learning in planning programmes to prevent and treat depressive symptoms in adolescence. PMID- 26377349 TI - Tob1 enhances radiosensitivity of breast cancer cells involving the JNK and p38 pathways. AB - The aim of the present study was to evaluate the effect of Tob1 on the radiosensitivity of breast cancer cells. The results showed that overexpression of Tob1 reduced the clonogenic growth of 231 cells and induced the rate of apoptosis. Tob1 caused an accumulation of cells in the G0 /G1 phase and decreased the percentage of cells in S phase. We also found that overexpression of Tob1 significantly reduced the phosphorylation of JNK and p38. The activator of JNK and p38, anisomycin, attenuated the blockage of Tob1 on the cell cycle and reversed the effect of Tob1 on apoptosis. Taken together, Tob1 enhanced radiosensitivity of breast cancer cells through regulation of the JNK and p38 pathways. The results indicated that Tob1 might be a promising molecular in gene therapy for the treatment of breast cancer. PMID- 26377350 TI - Effectiveness of follow-up reminiscence therapy on autobiographical memory in pathological ageing. AB - The objective is to examine the effects of reminiscence therapy (RT) on total, episodic and semantic autobiographical memory in amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD) groups, testing the effects of RT on different stages of autobiographical memory, and its effectiveness at follow up. A sample composed of 43 aMCI (27 treatments, 16 controls) and 30 AD (15 treatments, 15 controls) subjects were evaluated with the Autobiographical Memory Interview (AMI) test. The RT consisted of 10 sessions lasting 60 minutes each. Both groups, aMCI and AD, showed significant effects on overall autobiographical memory; aMCI showed significant main effects on episodic and semantic autobiographical memory in the treatment group, increasing scores in both cases. For AD, significant effects were observed on autobiographical episodic memory, showing an increase in the treatment group from Time 1 to follow-up; semantic memory showed a decrease in the control group from Time 1 to follow-up. Results show that RT implementation and follow-up are effective in increasing autobiographical memory in subjects with aMCI and AD. PMID- 26377351 TI - Periodontal Disease Is Associated with Insomnia among Victims of the Great East Japan Earthquake: A Panel Study Initiated Three Months after the Disaster. AB - In March 2011, the Great East Japan Earthquake (GEJE), which was followed by a devastating tsunami, destroyed the societal and the public hygiene systems in Japanese coastal areas. Insomnia, the greatest issue among disaster victims, has detrimental effects on both physical and psychological health. Periodontitis causes chronic discomfort and inflammation, and little is known about its impact on insomnia. Three months after the earthquake, a health panel survey was conducted over four surveys, till September 2013, in which information regarding 8,015 adults was collected and used. In addition to the heath-related questionnaire, other variables including subjective symptoms of oral diseases were recorded, and the Athens Insomnia Scale was used to evaluate the severity of insomnia. The association between insomnia and periodontal disease was examined using multilevel logistic models on the panel data, after adjusting for sex, age, economic status, comorbidities, body mass index, post-traumatic stress reactions, habitual smoking and alcohol drinking, and the Kessler Psychological Distress Scale score. In addition to the higher prevalence of insomnia among GEJE victims, significant association was revealed between insomnia and gum problems (OR = 2.16, 95% CI = 1.43-3.26), and difficulty chewing (OR = 2.22, 95% CI = 1.40 3.51), after adjusting for all covariates. The present study revealed significant association between insomnia and periodontal disease among GEJE victims. This indicated that together, integrated oral health care for disaster victims would contribute not only to prevention of oral infectious diseases, but may also help alleviate other problems caused by these harmful events. PMID- 26377353 TI - Complete separation of macroscopic rod-like bimetallic nanoassembly perpendicular and parallel on substrate for simultaneous sensing of microorganisms. AB - Although two kinds of macroscopic ordered tridimensional nanoassemblies, i.e., alignment of nanorods, can be yielded by controllable droplet evaporation methods, complete separation of the nanoassembly perpendicular or parallel to substrate is quite challenging. It can, however, be realized by the aid of facet blocking combined with the tuning of ionic strength and colloidal concentration. The as-fabricated rod-like bimetallic nanoassembly has proved to be an excellent SERS active substrate compared to random aggregates. It should be mentioned that macroscopic ordered tridimensional nanoassembly perpendicular to the substrate can be used as a highly active SERS substrate with good uniformity and can be successfully applied for finely discriminating two microorganisms: Escherichia coli bacteria and Saccharomycetes. PMID- 26377352 TI - Food Insecurity Increases the Odds of Obesity Among Young Hispanic Children. AB - Obesity is a growing public health concern and is more prevalent among low-income and minority populations. Food insecurity may increase the odds of obesity in children. We investigated the association between food insecurity and obesity among low-income, Hispanic, mother-child dyads (n = 74). The United States Department of Agriculture 18-item Household Food Security Survey was used to determine food security status. The majority of households were food insecure (74 %) and one-third (30 %) of children were obese. Food insecurity increased the odds of childhood obesity (OR 10.2; 95 % CI 1.2, 85.5) with stronger associations found within households where mothers were also overweight/obese compared to normal weight (p-for interaction < 0.05). Rates of household food insecurity and childhood obesity were high among this low-income Hispanic sample. Future studies should elucidate the mechanisms through which food insecurity impacts childhood obesity. PMID- 26377354 TI - Dextran-5-(4-ethoxycarbonylphenylazo)salicylic acid ester, a polymeric colon specific prodrug releasing 5-aminosalicylic acid and benzocaine, ameliorates TNBS induced rat colitis. AB - Local anesthetics have beneficial effects on colitis. Dextran-5-(4 ethoxycarbonylphenylazo)salicylic acid ester (Dex-5-ESA), designed as a polymeric colon-specific prodrug liberating 5-ASA and benzocaine in the large intestine, was prepared and its therapeutic activity against colitis was evaluated using a TNBS-induced rat colitis model. Dex-5-ESA liberated 5-ASA and benzocaine in the cecal contents while (bio)chemically stable in the small intestinal contents and mucosa. Oral administration of Dex-5-ESA (equivalent to 10 mg 5-ASA/kg, twice a day) alleviated colonic injury and reduced MPO activity in the inflamed colon. In parallel, pro-inflammatory mediators, COX-2, iNOS and CINC-3, elevated by TNBS induced colitis, were substantially diminished in the inflamed colon. Dex-5-ESA was much more effective for the treatment of colitis than 5-(4 ethoxycarbonylphenylazo)salicylic acid (5-ESA) that may not deliver benzocaine to the large intestine. Our data suggest that Dex-5-ESA is a polymeric colon specific prodrug, liberating 5-ASA and benzocaine in the target site (large intestine), probably exerting anti-colitic effects by combined action of 5-ASA and benzocaine. PMID- 26377355 TI - Prevalence and determinants of white coat effect in a large UK hypertension clinic population. AB - White coat hypertension (WCH) is common and termed white coat effect (WCE) in those on treatment for hypertension. The UK guideline suggests that all patients in stage 1 and 2 hypertension, but not stage 3 hypertension, should have ambulatory blood pressure monitoring (ABPM) performed before commencing treatment. The relationship between office blood pressure (BP) and ABPM and the factors that influence the WCE were examined in a large British cohort (n=2056) from 2 hypertension clinics (1998-2011). Data were collected prospectively: the median age was 56 years: 53% were female, 76% Caucasian, 9% African Caribbean, 15% South Asian and 86% taking antihypertensives. Fifty-one percent had WCE and differences between clinic BP and ABPM measurements increased with the stage of hypertension varying from 2/4 (normotensive), 13/10 (stage 1 hypertension), 24/14 (stage 2) and 40/20 mm Hg (stage 3). The degree of difference is greater in this study than described in other populations. A positive correlation was found between clinic systolic and diastolic BP and the WCE (r=0.74 and r=0.56, respectively, P<0.0001). Significant (P<0.05) independent associations of systolic WCE were clinic systolic BP (beta=0.707), Caucasian ethnicity (South Asian beta=-0.06; African Caribbean beta=-0.043), female gender (male beta= 0.047), nonsmoking status (smoker beta=-0.100) and reduced renal function (estimated glomerular filtration rate beta=-0.036). Significant independent associations of diastolic WCH were clinic diastolic BP (beta=0.624), age (beta=0.207), female gender (male beta=-0.104), Caucasian ethnicity (South Asian beta=-0.052, African Caribbean beta=-0.079) and being a nonsmoker (beta=-0.082) or ex-smoker (beta=0.046). The results support current UK guidelines but suggest those with stage 3 hypertension would also benefit from ABPM. PMID- 26377356 TI - Hypertension in Sub-Saharan Africa; prevalence, prescriptions, pitfalls and paradigms. PMID- 26377357 TI - Finding the Optimal Conditioning Regimen for Relapsed/Refractory Lymphoma Patients Undergoing Autologous Hematopoietic Cell Transplantation: A Retrospective Comparison of BEAM and High-Dose ICE. AB - OBJECTIVE: High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (AHCT) is a well-defined treatment modality for relapsed/refractory non-Hodgkin's lymphoma (NHL) and Hodgkin's lymphoma (HL). Although there are several options in terms of conditioning regimens before AHCT, no one treatment is accepted as a standard of care. This study aimed to compare different conditioning regimens for the treatment of NHL and HL.? MATERIALS AND METHODS: Medical records of 62 patients who had undergone AHCT following BEAM (BCNU, etoposide, cytarabine, and melphalan) and high-dose ICE (hICE; ifosfamide, carboplatin, and etoposide) conditioning regimens were analyzed retrospectively and compared in terms of efficacy and adverse effects.? ? RESULTS: The study included a total of 29 and 33 patients diagnosed with relapsed/refractory NHL and HL, respectively. Patients received BEAM (n=37) or hICE (n=25) regimens for conditioning. One-year overall survival was 73+/-6% in all patients. One-year overall survival was 71+/-8% and 74+/-9% in the BEAM and hICE groups, respectively (p=0.86). The incidences of nausea/vomiting (grade >=2) (84% vs. 44.7%; p=0.04) and mucositis (grade >=2) (13% vs. 3%; p=0.002) were higher in the hICE group compared to the BEAM group. In addition, we witnessed significantly more hepatotoxicity of grade >=2 (40% vs. 2.7%; p<0.005) and nephrotoxicity of grade >=2 (48% vs. 2.7%; p<0.005) among patients who received hICE. Significantly more patients (n=4; 25%) in the hICE group experienced veno-occlusive disease (VOD) compared to the BEAM arm, where no patients developed VOD (p=0.01). CONCLUSION: There was no difference in terms of overall survival between the BEAM and hICE groups. We observed significantly more adverse effects among patients treated with hICE. The BEAM regimen seems to be superior to hICE in terms of toxicity profile with comparable efficacy in patients with relapsed/refractory NHL and HL. PMID- 26377358 TI - Thermal Dehydrogenation of Base-Stabilized B2H5(+) Complexes and Its Role in C-H Borylation. AB - Thermally induced dehydrogenation of the H-bridged cation L2B2H5(+) (L=Lewis base) is proposed to be the key step in the intramolecular C-H borylation of tertiary amine boranes activated with catalytic amounts of strong "hydridophiles". Loss of H2 from L2B2H5(+) generates the highly reactive cation L2B2H3(+), which in its sp(2)-sp(3) diborane(4) form then undergoes either an intramolecular C-H insertion with B-B bond cleavage, or captures BH3 to produce L2B3H6(+). The effect of the counterion stability on the outcome of the reaction is illustrated by formation of LBH2C6F5 complexes through disproportionation of L2B2H5(+) HB(C6F5)3(-) . PMID- 26377359 TI - Heparin: 100 years of pleiotropic effects. AB - Heparin is a glycosaminoglycan with anticoagulant properties and antiinflammatory effects. The discovery of heparin approaches its 100th year and its antiinflammatory properties still draws much attention and anticipation to new possibilities of use and the likelihood of developing heparin-like drugs that lacked the anticoagulation effects. It is known that heparins limit the embolization and the extension of the thrombus, although they do not promote its complete lysis in most cases. The complexity and pleiotropic characteristics of these glycosaminoglycans still challenge science, to the point in which approaches hitherto unusual appear repeatedly in the literature. New indications, accompanied by longtime consecrated others, dismantle the idea of an outdated medication and create high expectations for the near future. The objective of this review is to analyze the pleiotropic effects of heparin and its use in several diseases, highlighting its safety and effectiveness. PMID- 26377360 TI - Lawsonia intracellularis infection of intestinal crypt cells is associated with specific depletion of secreted MUC2 in goblet cells. AB - The expression patterns of secreted (MUC2 and MUC5AC) and membrane-tethered (MUC1, MUC4, MUC12 and MUC13) mucins were monitored in healthy pigs and pigs challenged orally with Lawsonia intracellularis. These results showed that the regulation of mucin gene expression is distinctive along the GI tract of the healthy pig, and may reflect an association between the function of the mucin subtypes and different physiological demands at various sites. We identified a specific depletion of secreted MUC2 from goblet cells in infected pigs that correlated with the increased level of intracellular bacteria in crypt cells. We concluded that L. intracellularis may influence MUC2 production, thereby altering the mucus barrier and enabling cellular invasion. PMID- 26377361 TI - Azidopropylvinylsulfonamide as a New Bifunctional Click Reagent for Bioorthogonal Conjugations: Application for DNA-Protein Cross-Linking. AB - N-(3-Azidopropyl)vinylsulfonamide was developed as a new bifunctional bioconjugation reagent suitable for the cross-linking of biomolecules through copper(I)-catalyzed azide-alkyne cycloaddition and thiol Michael addition reactions under biorthogonal conditions. The reagent is easily clicked to an acetylene-containing DNA or protein and then reacts with cysteine-containing peptides or proteins to form covalent cross-links. Several examples of bioconjugations of ethynyl- or octadiynyl-modified DNA with peptides, p53 protein, or alkyne-modified human carbonic anhydrase with peptides are given. PMID- 26377362 TI - Preparation of chitosan-modified silica nanoparticles and their applications in the separation of auxins by capillary electrophoresis. AB - In recent years, nanoparticles have gained more attention when used in separation science. In this study, chitosan-modified silica nanoparticles were successfully synthesized and characterized by transmission electron microscopy, elemental analysis and zeta potential measurements, etc. When added into the running buffer solution as pseudo-stationary phase in capillary electrophoresis, the separation of four representative auxins, i.e., indole-3-acetic acid, indole butyric acid, 2,4-dichlorophenoxyacetic acid, 1-naphthaleneacetic acid, was carried out. Some important factors, such as the nanoparticles concentration, the pH and concentration of the running buffer solution, were also investigated on the separation. Under optimized experimental conditions, all the auxins investigated can be baseline separated within 5 min with higher column performance. The method established can also be used for quantitative analysis. The relative standard deviations obtained for indole-3-acetic acid, indole butyric acid, 2,4 dichlorophenoxyacetic acid, 1-naphthaleneacetic acid were in the range of 1.6 5.7% for peak area and 0.53-1.60% for migration time. The calibration curves obtained from the peaks areas for auxins were linear in the range of 0.1-80 mg/L with the correlation coefficients of 0.994-0.999. The limit of detection (S/N = 3) was 11-75 MUg/L. The developed method was also successfully used for the determination of auxins in fruits and vegetables samples with good recoveries. PMID- 26377363 TI - T-Cell Lymphoma Presenting with Auricular and Parotid Gland Involvement. PMID- 26377364 TI - Peptides in the presence of aqueous ionic liquids: tunable co-solutes as denaturants or protectants? AB - We studied the stability of a small beta-hairpin peptide under the influence of an aqueous 1-ethyl-3-methylimidazolium acetate ([EMIM](+)[ACE](-)) solution via all-atom molecular dynamics simulations in combination with metadynamics. Our free energy results indicate a denaturation of the peptide structure in the presence of the ionic liquid which is validated by a significant broadening of the end-to-end distance. The radial distribution functions between the ions and the peptide were used for the calculation of the preferential binding coefficients in terms of the Kirkwood-Buff theory. A significant structure dependent binding behavior of acetate to the peptide was found which can be interpreted as the main reason for the denaturation of the native conformation. The outcomes of our simulations allow us to propose a simple mechanism to explain the unfolding of the peptide with regard to the specific properties of ionic liquids. Our results are in good agreement with experimental findings and demonstrate the benefits of ionic liquids as tunable co-solutes with regard to their influence on protein structural properties. PMID- 26377366 TI - Anatomical Repair of an Unusual Combination of Tetralogy of Fallot and Atrioventricular Septal Defect With Unroofed Coronary Sinus. AB - A 30-month-old female was admitted with recurrent spells and severe cyanosis. Preoperative echocardiography was diagnostic of tetralogy of Fallot with an atrial septal defect of the primum type, unroofed coronary sinus, and a left superior vena cava draining into the left atrium. At surgery the patient was found to have a complete atrioventricular septal defect in addition to these anomalies. Complete anatomical correction was achieved through the right atrial approach. PMID- 26377365 TI - Protein phosphatase methylesterase-1 (PME-1) expression predicts a favorable clinical outcome in colorectal cancer. AB - Colorectal cancer (CRC) accounts for high mortality. So far, there is lack of markers capable of predicting which patients are at risk of aggressive course of the disease. Protein phosphatase-2A (PP2A) inhibitor proteins have recently gained interest as markers of more aggressive disease in certain cancers. Here, we report the role of PP2A inhibitor PME-1 in CRC. PME-1 expression was assessed from a rectal cancer patient cohort by immunohistochemistry, and correlations were performed for various clinicopathological variables and patient survival. Rectal cancer patients with higher cytoplasmic PME-1 protein expression (above median) had less recurrences (P = 0.003, n = 195) and better disease-free survival (DFS) than the patients with low cytoplasmic PME-1 protein expression (below median). Analysis of PPME-1 mRNA expression from TCGA dataset of colon and rectal adenocarcinoma (COADREAD) patient cohort confirmed high PPME1 expression as an independent protective factor predicting favorable overall survival (OS) (P = 0.005, n = 396) compared to patients with low PPME1 expression. CRC cell lines were used to study the effect of PME-1 knockdown by siRNA on cell survival. Contrary to other cancer types, PME-1 inhibition in CRC cell lines did not reduce the viability of cells or the expression of active phosphorylated AKT and ERK proteins. In conclusion, PME-1 expression predicts for a favorable outcome of CRC patients. The unexpected role of PME-1 in CRC in contrast with the oncogenic role of PP2A inhibitor proteins in other malignancies warrants further studies of cancer-specific function for each of these proteins. PMID- 26377367 TI - Chimeric Antigen Receptor T Cell Therapy in Hematology. AB - It is well demonstrated that the immune system can control and eliminate cancer cells. Immune-mediated elimination of tumor cells has been discovered and is the basis of both cancer vaccines and cellular therapies including hematopoietic stem cell transplantation. Adoptive T cell transfer has been improved to be more specific and potent and to cause less off-target toxicity. Currently, there are two forms of engineered T cells being tested in clinical trials: T cell receptor (TCR) and chimeric antigen receptor (CAR) modified T cells. On 1 July 2014, the United States Food and Drug Administration granted 'breakthrough therapy' designation to anti-CD19 CAR T cell therapy. Many studies were conducted to evaluate the benefits of this exciting and potent new treatment modality. This review summarizes the history of adoptive immunotherapy, adoptive immunotherapy using CARs, the CAR manufacturing process, preclinical and clinical studies, and the effectiveness and drawbacks of this strategy. PMID- 26377368 TI - Atomoxetine Treatment Strengthens an Anti-Correlated Relationship between Functional Brain Networks in Medication-Naive Adults with Attention-Deficit Hyperactivity Disorder: A Randomized Double-Blind Placebo-Controlled Clinical Trial. AB - BACKGROUND: Although atomoxetine demonstrates efficacy in individuals with attention-deficit hyperactivity disorder, its treatment effects on brain resting state functional connectivity remain unknown. Therefore, we aimed to investigate major brain functional networks in medication-naive adults with attention-deficit hyperactivity disorder and the efficacy of atomoxetine treatment on resting-state functional connectivity. METHODS: After collecting baseline resting-state functional MRI scans from 24 adults with attention-deficit hyperactivity disorder (aged 18-52 years) and 24 healthy controls (matched in demographic characteristics), the participants with attention-deficit hyperactivity disorder were randomly assigned to atomoxetine (n=12) and placebo (n=12) arms in an 8 week, double-blind, placebo-controlled trial. The primary outcome was functional connectivity assessed by a resting-state functional MRI. Seed-based functional connectivity was calculated and compared for the affective, attention, default, and cognitive control networks. RESULTS: At baseline, we found atypical cross talk between the default, cognitive control, and dorsal attention networks and hypoconnectivity within the dorsal attention and default networks in adults with attention-deficit hyperactivity disorder. Our first-ever placebo-controlled clinical trial incorporating resting-state functional MRI showed that treatment with atomoxetine strengthened an anticorrelated relationship between the default and task-positive networks and modulated all major brain networks. The strengthened anticorrelations were associated with improving clinical symptoms in the atomoxetine-treated adults. CONCLUSIONS: Our results support the idea that atypical default mode network task-positive network interaction plays an important role in the pathophysiology of adult attention-deficit hyperactivity disorder. Strengthening this atypical relationship following atomoxetine treatment suggests an important pathway to treat attention-deficit hyperactivity disorder. PMID- 26377369 TI - Some Health States Are Better Than Others: Using Health State Rank Order to Improve Probabilistic Analyses. AB - BACKGROUND: Probabilistic sensitivity analyses (PSA) may lead policy makers to take nonoptimal actions due to misestimates of decision uncertainty caused by ignoring correlations. We developed a method to establish joint uncertainty distributions of quality-of-life (QoL) weights exploiting ordinal preferences over health states. METHODS: Our method takes as inputs independent, univariate marginal distributions for each QoL weight and a preference ordering. It establishes a correlation matrix between QoL weights intended to preserve the ordering. It samples QoL weight values from their distributions, ordering them with the correlation matrix. It calculates the proportion of samples violating the ordering, iteratively adjusting the correlation matrix until this proportion is below an arbitrarily small threshold. We compare our method with the uncorrelated method and other methods for preserving rank ordering in terms of violation proportions and fidelity to the specified marginal distributions along with PSA and expected value of partial perfect information (EVPPI) estimates, using 2 models: 1) a decision tree with 2 decision alternatives and 2) a chronic hepatitis C virus (HCV) Markov model with 3 alternatives. RESULTS: All methods make tradeoffs between violating preference orderings and altering marginal distributions. For both models, our method simultaneously performed best, with largest performance advantages when distributions reflected wider uncertainty. For PSA, larger changes to the marginal distributions induced by existing methods resulted in differing conclusions about which strategy was most likely optimal. For EVPPI, both preference order violations and altered marginal distributions caused existing methods to misestimate the maximum value of seeking additional information, sometimes concluding that there was no value. CONCLUSIONS: Analysts can characterize the joint uncertainty in QoL weights to improve PSA and value-of information estimates using Open Source implementations of our method. PMID- 26377371 TI - Theoretical Investigation of the Methanol Decomposition by Fe+)and Fe(C2H4)+: A pi-Type Ligand Effect. AB - Density functional theory has been used to probe the mechanism of gas-phase methanol decomposition by bare Fe(+) and ligated Fe(C(2)H(4))(+) in both quartet and sextet states. For the Fe(+)/methanol system, Fe(+) could directly attach to the O and methyl-H atoms of methanol, respectively, forming two encounter isomers. The methanol reaction with Fe(+) prefers initial C-O bond activation to yield methyl with slight endothermicity, whereas CH(4) elimination is hindered by the strong endothermicity and high-energy barrier of hydroxyl-H shift. For the Fe(C(2)H(4))(+)/methanol system, the major product of H(2)O is formed through six elementary steps: encounter complexation, C-O bond activation, C-C coupling, beta H shift, hydride H shift, and nonreactive dissociation. Both ligand exchange and initial C-O bond activation mechanisms could account for ethylene elimination with the ion products Fe(CH(3)OH)(+) and (CH(3))Fe(OH)(+), respectively. With the assistance of a pi-type C(2)H(4) ligand, the metal center in the Fe(C(2)H(4))(+)/CH(3)OH system avoids formation of unfavorable multi-sigma-type bonding and thus greatly enhances the reactivity compared to that of bare Fe(+). PMID- 26377370 TI - A Framework for Including Family Health Spillovers in Economic Evaluation. AB - Health care interventions may affect the health of patients' family networks. It has been suggested that these "health spillovers" should be included in economic evaluation, but there is not a systematic method for doing this. In this article, we develop a framework for including health spillovers in economic evaluation. We focus on extra-welfarist economic evaluations where the objective is to maximize health benefits from a health care budget (the "health care perspective"). Our framework involves adapting the conventional cost-effectiveness decision rule to include 2 multiplier effects to internalize the spillover effects. These multiplier effects express the ratio of total health effects (for patients and their family networks) to patient health effects. One multiplier effect is specified for health benefit generated from providing a new intervention, one for health benefit displaced by funding this intervention. We show that using multiplier effects to internalize health spillovers could change the optimal funding decisions and generate additional health benefits to society. PMID- 26377373 TI - Boronate affinity materials for separation and molecular recognition: structure, properties and applications. AB - Boronate affinity materials, as unique sorbents, have emerged as important media for the selective separation and molecular recognition of cis-diol-containing compounds. With the introduction of boronic acid functionality, boronate affinity materials exhibit several significant advantages, including broad-spectrum selectivity, reversible covalent binding, pH-controlled capture/release, fast association/desorption kinetics, and good compatibility with mass spectrometry. Because cis-diol-containing biomolecules, including nucleosides, saccharides, glycans, glycoproteins and so on, are the important targets in current research frontiers such as metabolomics, glycomics and proteomics, boronate affinity materials have gained rapid development and found increasing applications in the last decade. In this review, we critically survey recent advances in boronate affinity materials. We focus on fundamental considerations as well as important progress and new boronate affinity materials reported in the last decade. We particularly discuss on the effects of the structure of boronate ligands and supporting materials on the properties of boronate affinity materials, such as binding pH, affinity, selectivity, binding capacity, tolerance for interference and so on. A variety of promising applications, including affinity separation, proteomics, metabolomics, disease diagnostics and aptamer selection, are introduced with main emphasis on how boronate affinity materials can solve the issues in the applications and what merits boronate affinity materials can provide. PMID- 26377372 TI - Morphological, Histological, and Molecular Description of Unicauda fimbrethilae n. sp. (Cnidaria: Myxosporea: Myxobolidae) from the Intestinal Tract of Channel Catfish Ictalurus punctatus. AB - The channel catfish Ictalurus punctatus is a known host for 10 species of Henneguya, but few other myxozoan genera are described from this species. Unicauda is a genus of myxozoan parasites within the family Myxobolidae that consists of 10 valid species from freshwater fish. Herein, we describe a novel species of Unicauda from the intestinal tract of farm-raised channel catfish in Mississippi. Myxospores were consistent with the genus Unicauda but exhibited a unique branching at the terminal end of the caudal process that has not previously been reported. Myxospores measured 90.39 +/- 14.97 MUm (mean +/- SD; range = 70.88-126.02 MUm) in total length. The spherical spore body measured 7.31 +/- 0.26 MUm (6.75-7.84 MUm) in length and 7.01 +/- 0.63 MUm (6.1-8.01 MUm) in width. The 2 polar capsules measured 3.45 +/- 0.33 MUm (3.02-4.03 MUm) in length and 2.65 +/- 0.32 MUm (2.18-3.11 MUm) in width. The single caudal process measured 82.98 +/- 14.97 MUm (63.39-118.63 MUm) in length from the base of the spore body to the end of the most terminal projection. Terminal projections measured 26.83 +/- 8.8 MUm (12.34-42.29 MUm) in length and 0.95 +/- 0.23 MUm (0.52-1.6 MUm) in width. The 18S rRNA gene sequence obtained did not match any published sequences. Given the uniqueness of the myxospore morphology, histological presentation, and gene sequence data, we describe this as an unreported species, Unicauda fimbrethilae n. sp. PMID- 26377374 TI - The in situ synthesis of Ag/amino acid biopolymer hydrogels as mouldable wound dressings. AB - This manuscript introduces a one-pot fabrication procedure for the preparation of supramolecular hybrid hydrogels from low-cost commercially available natural products through a "green" strategy. In particular, the hybrid hydrogels, which are developed with Fmoc-Glu-OMe, silver nanoparticles and chitosan, exhibit outstanding antibacterial properties and can be regarded as excellent mouldable wound healing biomaterials. PMID- 26377375 TI - Cost effectiveness of bronchial thermoplasty in patients with severe uncontrolled asthma. AB - RATIONALE: Based on its clinical effectiveness, bronchial thermoplasty (BT) was approved by the Food and Drug Administration in 2010 for the treatment of severe persistent asthma in patients 18 years and older whose asthma is not well controlled with inhaled corticosteroids and long-acting beta-agonist medicines. OBJECTIVE: Assess the 10 year cost-effectiveness of BT for individuals with severe uncontrolled asthma. METHODS: Using a Markov decision analytic model, the cost-effectiveness of BT was estimated. The patient population involved a hypothetical cohort of 41-year-old patients comparing BT to usual care over a 10 year time frame. The main outcome measure was cost in 2013 dollars per additional quality adjusted life year (QALY). RESULTS: Treatment with BT resulted in 6.40 QALYs and $7512 in cost compared to 6.21 QALYs and $2054 for usual care. The incremental cost-effectiveness ratio for BT at 10 years was $29,821/QALY. At a willingness to pay per QALY of $50,000, BT continues to be cost effective unless the probability of severe asthma exacerbation drops below 0.63 exacerbation per year or the cost of BT rises above $10,384 total for all three bronchoscopic procedures needed to perform thermoplasty and to cover the entire bronchial tree (baseline = $6690). CONCLUSIONS: BT is a cost-effective treatment for asthmatics at high risk of exacerbations. Continuing to follow asthmatics treated with BT beyond 5 years will help inform longer efficacy and support its cost effectiveness. PMID- 26377376 TI - Evaluation of Automated Volumetric Cartilage Quantification for Hip Preservation Surgery. AB - Automating the process of femoroacetabular cartilage identification from magnetic resonance imaging (MRI) images has important implications to guiding clinical care by providing a temporal metric that allows for optimizing the timing for joint preservation surgery. In this paper, we evaluate a new automated cartilage segmentation method using a time trial, segmented volume comparison, overlap metrics, and Euclidean distance mapping. We report interrater overlap metrics using the true fast imaging with steady-state precession MRI sequence of 0.874, 0.546, and 0.704 for the total overlap, union overlap, and mean overlap, respectively. This method was 3.28* faster than manual segmentation. This technique provides clinicians with volumetric cartilage information that is useful for optimizing the timing for joint preservation procedures. PMID- 26377377 TI - Risk of Acute Kidney Injury After Primary and Revision Total Hip Arthroplasty and Total Knee Arthroplasty Using a Multimodal Approach to Perioperative Pain Control Including Ketorolac and Celecoxib. AB - Safe and effective perioperative analgesia is instrumental to patient satisfaction and decreasing LOS after TJA. We evaluated rates of acute kidney injury (AKI) in primary and revision TJA using a multimodal pain control regimen including scheduled celecoxib and PRN ketorolac. Postoperative AKI was identified in 43/903 (4.8%) of 903 of patients with adequate preoperative renal function. Those who developed AKI had significantly increased LOS (P < .01), were older, more obese, and more likely to have diabetes (P < .05). With a protocol incorporating NSAIDs in patients without evidence of preoperative renal impairment, there is a 4.8% rate of AKI, which is 2.7 times higher than the reported literature. Acute postoperative kidney injury was significantly correlated with increased LOS and has important patient safety and healthcare related cost implications. PMID- 26377378 TI - An insight into the natural history of spinocerebellar ataxias. PMID- 26377380 TI - Editor's Letter. PMID- 26377379 TI - Long-term disease progression in spinocerebellar ataxia types 1, 2, 3, and 6: a longitudinal cohort study. AB - BACKGROUND: Spinocerebellar ataxias are dominantly inherited neurodegenerative diseases. As potential treatments for these diseases are being developed, precise knowledge of their natural history is needed. We aimed to study the long-term disease progression of the most common spinocerebellar ataxias: SCA1, SCA2, SCA3, and SCA6. Furthermore, we aimed to establish the order and occurrence of non ataxia symptoms, and identify predictors of disease progression. METHODS: In this longitudinal cohort study (EUROSCA), we enrolled men and women with positive genetic testing for SCA1, SCA2, SCA3, or SCA6 and with progressive, otherwise unexplained ataxia who were aged 18 years or older from 17 ataxia referral centres in ten European countries. Patients were seen every year for 3 years, and at irregular intervals thereafter. The primary outcome was the scale for the assessment and rating of ataxia (SARA), and the inventory of non-ataxia signs (INAS). We used linear mixed models to analyse progression. To account for dropouts, we applied a pattern-mixture model. This study is registered with ClinicalTrials.gov, number NCT02440763. FINDINGS: Between July 1, 2005, and Aug 31, 2006, 526 patients with SCA1, SCA2, SCA3, or SCA6 were enrolled. We analysed data for 462 patients with at least one follow-up visit. Median observation time was 49 months (IQR 35-72). SARA progression data were best fitted with a linear model in all genotypes. Annual SARA score increase was 2.11 (SE 0.12) in patients with SCA1, 1.49 (0.07) in patients with SCA2, 1.56 (0.08) in patients with SCA3, and 0.80 (0.09) in patients with SCA6. The increase of the number of non-ataxia signs reached a plateau in SCA1, SCA2, and SCA3. In patients with SCA6, the number of non-ataxia symptoms increased linearly, but more slowly than in patients with SCA1, SCA2, and SCA3 (p<0.0001). Factors that were associated with faster progression of the SARA score were short duration of follow-up (p=0.0179), older age at inclusion (0.04 [SE 0.02] per additional year; p=0.0476), and longer repeat expansions (0.06 [SE 0.02] per additional repeat unit; p=0.0128) in SCA1, short duration of follow-up (p<0.0001), lower age at onset (-0.02 [SE 0.01] per additional year; p=0.0014), and lower baseline SARA score (-0.02 [SE 0.01] per additional SARA point; p=0.0083) in SCA2, and lower baseline SARA score (-0.03 [SE 0.01] per additional SARA point; p=0.0195) in SCA6. In SCA3, we did not identify factors that affected progression of the SARA score. INTERPRETATION: Our study provides quantitative data on the progression of the most common spinocerebellar ataxias based on a follow-up period that exceeds those of previous studies. Our data could prove useful for sample size calculation and patient stratification in interventional trials. FUNDING: EU FP6 (EUROSCA), German Ministry of Education and Research (BMBF; GeneMove), Polish Ministry of Science, EU FP7 (NEUROMICS). PMID- 26377381 TI - Outbreak of Botulism After Consumption of Illicit Prison-Brewed Alcohol in a Maximum Security Prison--Arizona, 2012. AB - The authors investigated the second botulism outbreak to occur in a maximum security prison in Arizona within a 4-month period. Botulism was confirmed in eight men aged 20 to 35 years who reported sharing a single batch of pruno made with potatoes. Initial symptoms included blurred vision, slurred speech, muscle weakness, ptosis, and dysphagia. All patients received heptavalent botulinum antitoxin, seven required mechanical ventilation, and all survived. The median incubation period was 29 hours. Sera from all patients and leftover pruno tested positive for botulinum toxin type A. Botulism should be considered among prisoners with cranial nerve palsies and descending, symmetric flaccid paralysis. Prison-brewed alcohol, particularly when made with potatoes, can be a vehicle for botulism and is associated with outbreaks of botulism in prisons. PMID- 26377382 TI - When Caring for Perpetrators Becomes a Sentence: Recognizing Vicarious Trauma. AB - Correctional health nurses are not exempt from vicarious traumatization, but this concept has yet to be explored. Correctional health nurses practice in environments that come with significant risk for traumatic exposure from inmates and coworkers. The Professional Quality of Life Scale was used as a proxy to measure vicarious trauma. Surveys were mailed to 2,000 correctional health nurses that were on the mailing list of the National Commission on Correctional Health Care, with a total response rate of 10.1%. Respondents were asked to complete the Professional Quality of Life Scale and a short demographic survey. Findings reveal that vicarious traumatization does exist among correctional health nurses. PMID- 26377383 TI - The Use of Medically Recommended Intensive Supervision (Medical Parole) in Texas. AB - For more than 20 years, lawmakers in Texas acknowledged that offenders with special needs such as the elderly, physically handicapped, and mentally impaired who are housed in the Texas Department of Criminal Justice presented challenges in health care and cost. In response to these perceived needs, the Texas legislature created "medically recommended intensive supervision" (MRIS) to permit the early release of eligible offenders. This article examines how and why the MRIS law was implemented. It also discusses how MRIS is being utilized in Texas. Next, it delineates the MRIS process an offender must endure. The article elaborates on recent legislative attempts to amend the MRIS law. Finally, several conclusions about the use of MRIS in Texas are discussed. PMID- 26377386 TI - Resilience Patterns: Improving Stress Adaptation Based on an Individual's Personal Features. AB - Resilience, or the capacity to be able to develop oneself successfully despite adverse circumstances, has become a concept of interest in recent years. There is a clear relationship between resilience, psychological well-being, and coping strategies. This study looked at 890 subjects with a mean age of 46.77 (SD = 20.86) years, ranging from 18 and 95 years old. The participants were 40.6% men and 59.4% women. Using this sample, three clusters were developed by MATLAB R2010a and the Self-Organizing Maps toolbox. Two of these had high resilience, and the other one had low resilience; the psychological well-being variables and coping strategies were taken into account. Thereafter, multivariate analysis of variance showed a group effect for the resilience, psychological well-being, and coping strategies variables. Establishing resilient profiles based on variables such as psychological well-being and coping strategies reveals the best features for coping with stressful situations; this could help to promote nonpharmacological therapies for increasing resilience. PMID- 26377387 TI - Thermo/pH Dual Responsive Mixed-Shell Polymeric Micelles Based on the Complementary Multiple Hydrogen Bonds for Drug Delivery. AB - Thermo/pH dual responsive mixed-shell polymeric micelles based on multiple hydrogen bonding were prepared by self-assembly of diaminotriazine-terminated poly(E-caprolactone) (DAT-PCL), uracil-terminated methoxy poly(ethylene glycol) (MPEG-U), and uracil-terminated poly(N-vinylcaprolactam) (PNVCL-U) at room temperature. PCL acted as the core and MPEG/PNVCL as the mixed shell. Increasing the temperature, PNVCL collapsed and enclosed the PCL core, while MPEG penetrated through the PNVCL shell, thereby leading to the formation of MPEG channels on the micelles surface. The low cytotoxicity of the mixed micelles was confirmed by an MTT assay against BGC-823 cells. Studies on the in vitro drug release showed that a much faster release rate was observed at pH 5.0 compared to physiological pH, owing to the dissociation of hydrogen bonds. Therefore, the mixed-shell polymeric micelles would be very promising candidates in drug delivery systems. PMID- 26377388 TI - Enantioselective column coupled electrophoresis employing large bore capillaries hyphenated with tandem mass spectrometry for ultra-trace determination of chiral compounds in complex real samples. AB - A new multidimensional analytical approach for the ultra-trace determination of target chiral compounds in unpretreated complex real samples was developed in this work. The proposed analytical system provided high orthogonality due to on line combination of three different methods (separation mechanisms), i.e. (1) isotachophoresis (ITP), (2) chiral capillary zone electrophoresis (chiral CZE), and (3) triple quadrupole mass spectrometry (QqQ MS). The ITP step, performed in a large bore capillary (800 MUm), was utilized for the effective sample pretreatment (preconcentration and matrix clean-up) in a large injection volume (1-10 MUL) enabling to obtain as low as ca. 80 pg/mL limits of detection for the target enantiomers in urine matrices. In the chiral CZE step, the different chiral selectors (neutral, ionizable, and permanently charged cyclodextrins) and buffer systems were tested in terms of enantioselectivity and influence on the MS detection response. The performance parameters of the optimized ITP - chiral CZE QqQ MS method were evaluated according to the FDA guidance for bioanalytical method validation. Successful validation and application (enantioselective monitoring of renally eliminated pheniramine and its metabolite in human urine) highlighted great potential of this chiral approach in advanced enantioselective biomedical applications. PMID- 26377389 TI - An open randomised study of autoinflation in 4- to 11-year-old school children with otitis media with effusion in primary care. AB - BACKGROUND: Otitis media with effusion (OME) is a very common problem in primary care, but one that lacks an evidence-based non-surgical treatment. OBJECTIVE: To determine the clinical effectiveness of nasal balloon autoinflation for the treatment of OME in children. DESIGN: A pragmatic, two-arm, open randomised controlled trial. SETTING: Forty-three general practices from 17 UK primary care trusts recruited between January 2012 and February 2013. PARTICIPANTS: School children aged 4-11 years with a history of OME symptoms or related concerns in the previous 3 months, and a type B tympanogram, diagnostic of a middle ear effusion, in one or both ears. INTERVENTION: Three hundred and twenty children were randomised, 160 to each group, using independent web-based computer generated randomisation (with minimisation based on age, sex and baseline severity of OME) to either nasal balloon autoinflation performed three times per day for 1-3 months plus usual care, or usual care alone. MAIN OUTCOME MEASURES: The proportion of children demonstrating clearance of middle ear fluid in at least one ear (with normal tympanograms) at 1 and 3 months, assessed blind to treatment. An ear-related measure of quality of life (QoL) [a 14-point questionnaire on the impact of OME (OMQ-14)], weekly diary recorded symptoms, compliance and adverse events were all secondary outcomes. RESULTS: At 1 month, the proportion of children with normal tympanograms was 47.3% (62/131) in those allocated to autoinflation and 35.6% (47/132) in those receiving usual care [adjusted relative risk (RR) 1.36, 95% confidence interval (CI) 0.99 to 1.88]. At 3 months, the proportions were 49.6% (62/125) and 38.3% (46/120), respectively (adjusted RR 1.37, 95% CI 1.03 to 1.83; number needed to treat = 9). The change in OMQ-14 also favoured the intervention arm (adjusted global score difference 0.42; p = 0.001). Reported compliance was good: 89% in the first month and 80% in months 2 and 3. Adverse events included otalgia in 4% of treated children compared with 1% in the control group. Minor nosebleeds (14% vs. 15%) and respiratory tract infections (18% vs. 13%) were noted. CONCLUSION: We found the use of autoinflation in young children with OME to be feasible in primary care and effective in both clearing effusions and improving child and parent ear related QoL and symptoms. This method has scope to be used more widely. Further research is needed for very young children, and to inform prudent use in different health settings. PMID- 26377390 TI - Neuroinflammatory signals enhance the immunomodulatory and neuroprotective properties of multipotent adult progenitor cells. AB - INTRODUCTION: Stem cell-based therapies are currently widely explored as a tool to treat neuroimmune diseases. Multipotent adult progenitor cells (MAPC) have been suggested to have strong immunomodulatory and neuroprotective properties in several experimental models. In this study, we investigate whether MAPC are of therapeutic interest for neuroinflammatory disorders such as multiple sclerosis by evaluating their capacities to modulate crucial pathological features and gain insights into the molecular pathways involved. METHODS: Rat MAPC were treated with combinations of pro-inflammatory cytokines that are closely associated with neuroinflammatory conditions, a process called licensing. mRNA expression of immunomodulatory molecules, chemokines and chemokine receptors was investigated. The migratory potential of licensed rat MAPC towards a broad spectrum of chemokines was tested in a Transwell assay. Furthermore, the effect of licensing on the ability of rat MAPC to attract and suppress the proliferation of encephalitogenic T cells was assessed. Finally, neuroprotective properties of rat MAPC were determined in the context of protection from oxidative stress of oligodendrocytes. Therefore, rat MAPC were incubated with conditioned medium of OLN93 cells subjected to sublethal doses of hydrogen peroxide and the gene expression of neurotrophic factors was assessed. RESULTS: After licensing, a wide variety of immunomodulatory molecules and chemokines, including inducible nitric oxide synthase and fractalkine, were upregulated by rat MAPC. The migratory properties of rat MAPC towards various chemokines were also altered. In addition, rat MAPC were found to inhibit antigen-specific T-cell proliferation and this suppressive effect was further enhanced after pro-inflammatory treatment. This phenomenon was partially mediated through inducible nitric oxide synthase or cyclooxygenase-2. Activated rat MAPC secreted factors that led to attraction of myelin-specific T cells. Finally, exposure of rat MAPC to an in vitro simulated neurodegenerative environment induced the upregulation of mRNA levels of vascular endothelial growth factor and ciliary neurotrophic factor. Factors secreted by rat MAPC in response to this environment partially protected OLN93 cells from hydrogen peroxide-induced cell death. CONCLUSIONS: Rat MAPC possess immune modulatory and neuroprotective properties which are enhanced in response to neuroinflammatory signals. These findings thereby warrant further research to evaluate MAPC transplantation as a therapeutic approach in diseases with an immunological and neurodegenerative component such as multiple sclerosis. PMID- 26377391 TI - Factors affecting recurrence and prognosis after R0 resection for colorectal cancer with peritoneal metastasis. AB - BACKGROUND: Peritoneal metastases (PM) are a well-known poor prognostic factor. The aim of this study was to investigate the factors affecting recurrence and prognosis after R0 resection for colorectal cancer with synchronous peritoneal metastases. METHODS: We conducted a multi-institutional retrospective analysis of 72 patients without distant metastases who underwent R0 surgery between 1991 and 2007 for colorectal cancer with PM localized to the adjacent peritoneum. Clinicopathological variables were analyzed for their significance to recurrence and prognosis. RESULTS: Recurrence was found in 51 patients (70.8%) after R0 surgery. In logistic regression analyses, lymph node metastasis was shown to be an independent factor affecting recurrence. Non-intensive or no postoperative chemotherapy and eight or fewer dissected lymph nodes were identified as independent poor prognostic factors using the Cox proportional hazards model. Among patients who received postoperative chemotherapy, prognosis was significantly better in those who received intensive adjuvant chemotherapy using camptothecin-11 or oxaliplatin after R0 surgery than in those who received non intensive chemotherapy. Among 47 patients whose recurrence date was known, 33 patients (70.2%) experienced recurrence within 18 months after R0 surgery for peritoneal metastases, and hematogenous recurrence was observed significantly more often than peritoneal recurrence. CONCLUSIONS: Harvesting of more than eight lymph nodes and administration of intense adjuvant chemotherapy after R0 surgery are recommended for greater prediction accuracy and improved prognosis. Intensive follow-up should be performed within 18 months after R0 surgery for colorectal cancer with synchronous peritoneal metastases. PMID- 26377393 TI - Cochlear Function Monitoring after Spinal Anesthesia. AB - BACKGROUND: The aim of the study was to examine the effect of spinal anesthesia on the function of cochlear outer hair cells (OHCs), determined by means of objective distortion product otoacoustic emissions (DPOAE) testing. To the best of our knowledge, our study was the second OAE-based analysis of cochlear function during spinal anesthesia, and the only experiment including such a large group of patients. MATERIAL AND METHODS: The study included 20 patients (18 men and 2 women) subjected to a scheduled uretherorenoscopic lithotripsy with routine spinal anesthesia with 10 mg (2 ml) of 0.5% hyperbaric bupivacaine and 50 MUg (1 ml) of fentanyl. The levels of DPOAEs and background noise at 1000-6000 Hz were recorded prior to and immediately after the anesthesia, and on the postoperative day 2. RESULTS: We did not find significant differences between DPOAEs values recorded prior to and immediately after the anesthesia. The only exception pertained to 5652 Hz, at which a significantly higher level of DPOAEs was observed immediately after the anesthesia. The levels of DPOAEs at 2002 Hz and 2380 Hz collected on the postoperative day 2 were significantly higher than the respective baseline values. Irrespective of the frequency and time of testing, we did not find any significant differences between the recorded levels of background noise. CONCLUSIONS: Our findings point to the lack of a detrimental effect of spinal anesthesia on objectively evaluated cochlear function, and thus suggest that this method is safe, even for OHCs, which are extremely susceptible to exogenous and endogenous injuries. PMID- 26377392 TI - Myometrial contractility influences oxytocin receptor (OXTR) expression in term trophoblast cells obtained from the maternal surface of the human placenta. AB - BACKGROUND: Oxytocin (OXT) acts through its specific receptor (OXTR) and increased density of OXTR and/or augmented sensitivity to OXT were postulated as prerequisites of normal onset of labor. Expression of OXTR in the placental term trophoblast cells has not yet been analyzed in the context of contractile activity of the uterus. Here we examine comparatively OXT contents in the placental tissue adjacent to the uterine wall and expressions of OXTR in this tissue and corresponding isolated placental trophoblast cells. METHODS: Twenty eight placentae after normal labors at term (group I, N = 14) and after cesarean sections performed without uterine contractile activity (group II, N = 14) have been collected. Tissue excised from the maternal surface of examined placenta was used for OXT concentration measurement, cytotrophoblast cell cultures preparation and immunohistochemistry of OXTR. Concentration of OXT was estimated in the tissue homogenates by an enzyme immunoassay with colorimetric detection. Cytotrophoblast cells were isolated using Kliman's method based on trypsin, DNase, and a 5-70% Percoll gradient centrifugation. The cultures were incubated for 5 days in normoxia. Both placental specimens and terminated cytotrophoblast cultures were fixed and embedded in paraffin before being immunostained for OXTR. Using light microscopy with computed morphometry for quantitative analysis, OXTR expressions were estimated in calibrated areas of the paraffin sections. RESULTS: There were not significant differences between the groups in respect to the mean OXT concentration. However, in both groups the median value of OXT concentration was significantly (p < 0.05) higher in the tissue obtained from the peripheral regions of the maternal surface of the placenta, compared to the samples from the central region of this surface. In placental tissue the mean expression of OXTR in group I was significantly (p < 0.05) increased by approximately 3.2-fold and 3.45-fold (the samples collected from central and peripheral regions, respectively) compared to the values obtained in group II. In the isolated primary trophoblast cultures the differences were even more evident (p < 0.02) and the mean change in OXTR expression in group I comprised approximately 6.9 fold increase and 6.5-fold increase (the samples collected from central and peripheral regions, respectively) compared to the values obtained in group II. CONCLUSIONS: Upregulation of OXTR within placental trophoblast cells localized close or adherent to uterine wall may play a crucial role in labor with efficient contractile activity (vaginal delivery). Further studies may disclose if this local OXT/OXTR signaling is utilized in the third stage of labor to elicit placental detachment or contribute in a more versatile way throughout the labor period. PMID- 26377394 TI - Chronic oxycodone induces integrated stress response in rat brain. AB - BACKGROUND: Oxycodone is an opioid that is prescribed to treat multiple types of pain, especially when other opioids are ineffective. Unfortunately, similar to other opioids, repetitive oxycodone administration has the potential to lead to development of analgesic tolerance, withdrawal, and addiction. Studies demonstrate that chronic opioid exposure, including oxycodone, alters gene expression profiles and that these changes contribute to opioid-induced analgesic effect, tolerance and dependence. However, very little is known about opioids altering the translational machinery of the central nervous system. Considering that opioids induce clinically significant levels of hypoxia, increase intracellular Ca(2+) levels, and induce the production of nitric oxide and extracellular glutamate transmission, we hypothesize that opioids also trigger a defensive mechanism called the integrated stress response (ISR). The key event in the ISR activation, regardless of the trigger, is phosphorylation of translation initiation factor 2 alpha (eIF2alpha), which modulates expression and translational activation of specific mRNAs important for adaptation to stress. To test this hypothesis, we used an animal model in which female rats were orally gavaged with 15 mg/kg of oxycodone every 24 h for 30 days. RESULTS: We demonstrated increased levels of hsp70 and BiP expression as well as phosphorylation of eIF2alpha in various rat brain areas after oxycodone administration. Polysomal analysis indicated oxycodone-induced translational stimulation of ATF4 and PDGFRalpha mRNAs, which have previously been shown to depend on the eIF2alpha kinase activation. Moreover, using breast adenocarcinoma MCF7 cells, which are known to express the MU-opioid receptor, we observed induction of the ISR pathway after one 24-h treatment with oxycodone. CONCLUSIONS: The combined in vivo and in vitro data suggest that prolonged opioid treatment induces the integrated stress response in the central nervous system; it modulates translational machinery in favor of specific mRNA and this may contribute to the drug-induced changes in neuronal plasticity. PMID- 26377395 TI - The utility of Xpert MTB/RIF performed on bronchial washings obtained in patients with suspected pulmonary tuberculosis in a high prevalence setting. AB - BACKGROUND: Xpert MTB/RIF has been shown to have a superior sensitivity to microscopy for acid fast bacilli (AFB) in sputum and has been recommended as a standard first line investigation for pulmonary tuberculosis (PTB). Bronchoscopy is a valuable tool in diagnosing PTB in sputum negative patients. There is limited data on the utility of Xpert MTB/RIF performed on bronchial lavage specimens. Our aim was to evaluate the diagnostic efficiency of Xpert MTB/RIF performed on bronchial washings in sputum scarce/negative patients with suspected PTB. METHODS: All patients with a clinical and radiological suspicion of PTB who underwent bronchoscopy between January 2013 and April 2014 were included. The diagnostic efficiencies of Xpert MTB/RIF and microscopy for AFB were compared to culture for Mycobacterium tuberculosis. RESULTS: Thirty nine of 112 patients were diagnosed with culture-positive PTB. Xpert MTB/RIF was positive in 36/39 with a sensitivity of 92.3% (95% CI 78-98%) for PTB, which was superior to that of smear microscopy (41%; 95% CI 26.0-57.8%, p = 0.005). The specificities of Xpert MTB/RIF and smear microscopy were 87.7% (95% CI 77.4-93.9%) and 98.6% (95% CI 91.6%-99.9%) respectively. Xpert MTB/RIF had a positive predictive value of 80% (95% CI; 65-89.9%) and negative predictive value of 95.5% (95% CI 86.6-98.8%). 3/9 patients with Xpert MTB/RIF positive culture negative results were treated for PTB based on clinical and radiological findings. CONCLUSION: Xpert MTB/RIF has a higher sensitivity than smear microscopy and similar specificity for the immediate confirmation of PTB in specimens obtained by bronchial washing, and should be utilised in patients with a high suspicion of pulmonary tuberculosis. PMID- 26377396 TI - Using a verbal prompt to increase protein consumption in a hospital setting: a field study. AB - BACKGROUND: Sufficient protein intake among hospitalized patients may contribute to faster recovery and a decrease in healthcare costs. Nevertheless, hospitalized patients are often found to consume too little protein. This field study explored the success of a small, inexpensive intervention adapted from the marketing literature, to encourage protein consumption among hospitalized patients. METHODS: The study was performed at a hospital where patients order food by calling to the meal service. The intervention consisted of a verbal prompt: "Would you like some [target product] with that?", which was presented to patients by trained telephone operators, after patients finished ordering their lunch. Target products were two foods rich in protein; fruit quark and yoghurt drink. For half of the patients, the verbal prompt was preceded by verbal praise on their lunch order, which was aimed to increase compliance with the verbal prompt. RESULTS: Three hundred and fifteen hospitalized patients, aged 18-87 years took part in the study. Verbal prompts significantly increased ordering of the target products nearly sevenfold (from ordering by 6.5% of patients to 45.2% of patients). Protein content of ordered lunch and all food orders of the day combined showed a trend, with orders of patients receiving only a verbal prompt or a verbal prompt and verbal praise containing a larger amount of protein than lunch orders of patients in the control condition. At an individual level, protein content of ordered food increased significantly, reaching the 25-30 g of protein per main meal recommended by dieticians of the hospital. Verbal praise did not increase compliance with the verbal prompt. Patients consumed most or all of the target product and verbal prompts were not perceived to be obtrusive. CONCLUSIONS: Although changing eating patterns is challenging, this study shows that simple interventions such as verbal prompts may be useful tools for health professionals to stimulate healthy food consumption among patients during hospitalization. PMID- 26377398 TI - This editorial, which discusses currently unpublished research, was published due to an administrative error and has therefore been removed. PMID- 26377397 TI - Immune profile of an atypical EAE model in marmoset monkeys immunized with recombinant human myelin oligodendrocyte glycoprotein in incomplete Freund's adjuvant. AB - BACKGROUND: Experimental autoimmune encephalomyelitis (EAE) in the common marmoset monkey (Callithrix jacchus) is a relevant preclinical model for translational research into immunopathogenic mechanisms operating in multiple sclerosis (MS). Prior studies showed a core pathogenic role of T and B cells specific for myelin oligodendrocyte glycoprotein (MOG). However, in those studies, the quality of the response against MOG epitopes was strongly biased by bacterial antigens in the complete Freund's adjuvant (CFA), in which the immunizing recombinant human (rh) MOG protein had been formulated. In response to the need of a more refined EAE model, we have tested whether disease could also be induced with rhMOG in incomplete Freund's adjuvant (IFA). METHOD: Marmosets were immunized with rhMOG emulsified in IFA in the dorsal skin. Monkeys that did not develop neurological deficit were given booster immunizations at 28-day interval with the same antigen preparation. In a second experiment, three marmoset twin pairs were sensitized against MOG peptides in IFA to study a possibility for suppressive activity towards pathogenic T cells directed against the encephalitogenic epitope MOG40-48. RESULTS: Despite the absence of strong danger signals in the rhMOG/IFA inoculum, all monkeys developed clinically evident EAE symptoms. Moreover, in all monkeys, demyelinated lesions were present in the white matter and in two cases also in the cortical grey matter. Immune profiling at height of the disease showed a dominant T cell response against the overlapping peptides 14-36 and 24-46, but reactivity against the pathogenically most relevant peptide 34-56 was conspicuously absent. In the second experiment, there was an indication for a possible suppressive mechanism. CONCLUSIONS: Immunization of marmoset monkeys with rhMOG in IFA elicits clinical EAE in all animals. Moreover, rhMOG contains pathogenic and regulatory epitopes, but the pathogenic hierarchy of rhMOG epitopes is strongly influenced by the adjuvant in which the protein is formulated. PMID- 26377399 TI - Further evidence that high-density lipoprotein is a chameleon-like lipoprotein. PMID- 26377401 TI - One drug, two outcomes after atrial fibrillation ablation: the situational irony of adenosine. PMID- 26377400 TI - The comparative efficacy of bivalirudin is markedly attenuated by use of radial access: insights from Blue Cross Blue Shield of Michigan Cardiovascular Consortium. AB - AIM: The purpose of our study was to evaluate the relative impact of bivalirudin on bleeding outcomes associated with trans-radial interventions (TRI) in real world practice. METHODS AND RESULTS: Data for patients undergoing percutaneous coronary intervention (PCI) between January 2010 and March 2014 at the 47 hospitals participating in the Blue Cross Blue Shield of Michigan Cardiovascular Consortium (BMC2) were utilized. Propensity matching was used within cohorts defined by access site. The impact of bivalirudin use on in-hospital outcomes was evaluated with Fisher's exact tests. Among patients undergoing trans-femoral interventions (TFI), use of bivalirudin was associated with a reduction in bleeding compared with both glycoprotein IIb/IIIa inhibitors (GPI; 1.67 vs. 3.46%, absolute risk reduction (ARR) 1.79%, odds ratio, OR, 0.47, confidence interval, CI, 0.41-0.54, number needed to treat, NNT 56, P < 0.001) and heparin (1.26 vs. 1.76%, ARR 0.5%, OR 0.71, CI 0.61-0.82, NNT 197, P < 0.001). Among patients undergoing TRI, there was a more modest absolute reduction in bleeding with bivalirudin compared with GPI (0.79 vs. 1.41%, ARR 0.62%, OR 0.56, CI 0.34 0.90, NNT 161, P = 0.016) and no difference in bleeding compared with heparin (0.46 vs. 0.46%, OR 1, CI 0.54-1.84, P = 1). CONCLUSION: Bivalirudin is markedly efficacious in reducing bleeding in patients undergoing TFI. The reduction in bleeding associated with bivalirudin use is minimal to absent in patients undergoing TRI. Given its lower cost and comparable outcomes, heparin should be the preferred anticoagulation strategy in those undergoing radial PCI. PMID- 26377402 TI - Reply to the Letter. PMID- 26377403 TI - Regulation of nitrate and methylamine metabolism by multiple nitrogen sources in the methylotrophic yeast Candida boidinii. AB - The methylotrophic yeast Candida boidinii, which is capable of growth on methanol as a sole carbon source, can proliferate on the leaf surface of Arabidopsis thaliana. Previously, we demonstrated that adaptation to a change in the major available nitrogen source from nitrate to methylamine during the host plant aging was crucial for yeast survival on the leaf environment. In this report, we investigated the regulatory profile of nitrate and methylamine metabolism in the presence of multiple nitrogen sources in C. boidinii. The transcript level of nitrate reductase (Ynr1) gene was induced by nitrate and nitrite, and was not repressed by the coexistence with other nitrogen sources. In contrast, the transcript level of amine oxidase (Amo1) gene, which was induced by methylamine, was significantly repressed by the coexistence with ammonium or glutamine. In addition, we investigated the intracellular dynamics of Ynr1 during the nitrogen source shift from nitrate to other compounds. Under these tested conditions, Ynr1 was effectively transported to the vacuole via selective autophagy only during the shift from nitrate to methylamine. Moreover, Ynr1 was subject to degradation after the shift from nitrate to nitrate plus methylamine medium even though nitrate was still available. These regulatory profiles may reflect life style of nitrogen utilization in this yeast living in the phyllosphere. PMID- 26377404 TI - Precise cloning and tandem integration of large polyketide biosynthetic gene cluster using Streptomyces artificial chromosome system. AB - BACKGROUND: Direct cloning combined with heterologous expression of a secondary metabolite biosynthetic gene cluster has become a useful strategy for production improvement and pathway modification of potentially valuable natural products present at minute quantities in original isolates of actinomycetes. However, precise cloning and efficient overexpression of an entire biosynthetic gene cluster remains challenging due to the ineffectiveness of current genetic systems in manipulating large-sized gene clusters for heterologous as well as homologous expression. RESULTS: A versatile Escherichia coli-Streptomyces shuttle bacterial artificial chromosomal (BAC) conjugation vector, pSBAC, was used along with a cluster tandem integration approach to carry out homologous and heterologous overexpression of a large 80-kb polyketide biosynthetic pathway gene cluster of tautomycetin (TMC), which is a protein phosphatase PP1/PP2A inhibitor and T cell specific immunosuppressant. Unique XbaI restriction sites were precisely inserted at both border regions of the TMC biosynthetic gene cluster within the chromosome of TMC-producing Streptomyces sp. CK4412, followed by site-specific recombination of pSBAC into the flanking region of the TMC gene cluster. The entire TMC gene cluster was then rescued as a single giant recombinant pSBAC by XbaI digestion of the chromosomal DNA as well as subsequent self-ligation. Next, the recombinant pSBAC construct containing the entire TMC cluster in E. coli was directly conjugated into model Streptomyces strains, resulting in rapid and enhanced TMC production. Moreover, introduction of the TMC cluster-containing pSBAC into wild type Streptomyces sp. CK4412 as well as a recombinant S. coelicolor strain resulted in a chromosomal tandem repeat of the entire TMC cluster with 14-fold and 5.4-fold enhanced TMC productivities, respectively. CONCLUSIONS: The 80-kb TMC biosynthetic gene cluster was isolated in a single integration vector, pSBAC. Introduction of TMC biosynthetic gene cluster in TMC non-producing strains has resulted in similar amount of TMC production yield. Moreover, over-expression of TMC biosynthetic gene cluster in original producing strain and recombinant S. coelicolor dramatically increased TMC production. Thus, this strategy can be employed to develop a custom overexpression scheme of entire metabolite pathway clusters present in actinomycetes. PMID- 26377405 TI - Erratum to: Long-term safety and efficacy of antithymocyte globulin induction: use of integrated national registry data to achieve ten-year follow-up of 10-10 Study participants. PMID- 26377406 TI - Down-regulated MicroRNA 148b expression as predictive biomarker and its prognostic significance associated with clinicopathological features in non-small cell lung cancer patients. AB - BACKGROUND: Lung cancer is most common and is the leading cause of cancer-related death in both men and women worldwide. Understanding of the molecular mechanisms underlying non-small cell lung cancer (NSCLC) development and progression are important. In the present study, we investigated the potential role of miR-148b expression analysis as potential lung cancer biomarker with the correlation of circulating miR-148b to clinicopathological features. METHODS: A total of 104 NSCLC patients were diagnosed and cancer tissues together with adjacent normal tissues were evaluated. Quantitative Real-time PCR method was utilized to evaluate the expression levels of miR-148b. In addition, we investigated to clarify the relationship of miR-148b with clinicopathological features and survival in patients with NSCLC. RESULTS: Our findings showed that miR-148b was downregulated in tumor tissues when compared with corresponding adjacent normal lung tissues (0.34 +/- 0.13 vs. 1.00 +/- 0.57, P < 0.05). Moreover decreased expression of miR-148b was significantly related to TNM stage (P = 0.001) and lymph node-metastasis (P = 0.023). This findings suggested that miR-148b was down regulated in NSCLC patients and may play a key role as a tumor suppressor gene in NSCLC. Kaplan-Meier survival analysis and log-rank test suggested that low expression group of patients had significantly shorter overall survival than high expression group (log-rank test: P = 0.031). Multivariate Cox proportional hazards model analysis indicated that low miR-148b expression was independently linked to poor survival of patients with NSCLC (HR = 3.215, 95 % CI: 1.543 10.621, P = 0.021) and other factors were not significant independent predictor of survival in patients with NSCLC. CONCLUSION: Our findings demonstrated that miR-148b may play a role as independent prognostic factor for patients with NSCLC. PMID- 26377407 TI - A mutual titer-enhancing relationship and similar localization patterns between Citrus exocortis viroid and Hop stunt viroid co-infecting two citrus cultivars. AB - BACKGROUND: Citrus exocortis viroid (CEVd) and Hop stunt viroid (HSVd) are commonly found simultaneously infecting different citrus cultivars in Taiwan. A crucial question to be addressed is how accumulations of these two viroids affect each other in an infected plant. In this study, we investigated the relationship between the two viroids at macroscopic and microscopic levels. METHODS: CEVd and HSVd titers were examined by real-time RT-PCR in 17 plants of two citrus cultivars (blood orange and Murcott mandarin) every 3 months (spring, summer, fall and winter) from 2011 to 2013. Three nonparametric tests (Spearman's rank correlation coefficient, Kendall's tau rank correlation coefficient and Hoeffding's inequality) were performed to test the correlation between CEVd and HSVd. Cellular and subcellular localizations of the two viroids were detected by digoxigenin- and colloidal gold-labeled in situ hybridization using light and transmission electron microscopy. RESULTS: The two viroids were unevenly distributed in four different types of citrus tissues (rootstock bark, roots, twig bark and leaves). Compared with blood orange, Murcott mandarin was generally more susceptible to CEVd and HSVd infection. Both viroids replicated and preferentially accumulated in the underground tissues of the two citrus cultivars. Except for blood orange at high temperatures, significant positive correlations were observed between the two viroids in specific tissues of both cultivars. Relative to concentrations under single-infection conditions, the CEVd population significantly increased under double infection during half of the 12 monitored seasons; in contrast, the population of HSVd significantly increased under double infection during only one season. At cellular/subcellular levels, the two viroids showed similar localization patterns in four tissues and the cells of these tissues in the two citrus cultivars. CONCLUSIONS: Our findings of titer enhancement, localization similarity, and lack of symptom aggravation under CEVd and HSVd double infection suggest that the two viroids have a positive relationship in citrus. The combination of molecular and cellular techniques used in this study provided evidence of titer correlation and localization of co infecting viroids in the host. These methods may thus be useful tools for exploring viroid-viroid and viroid-host interactions. PMID- 26377408 TI - Definitive and adjuvant radiotherapy for sinonasal squamous cell carcinomas: a single institutional experience. AB - BACKGROUND: The aim of this study was to evaluate the disease outcomes of patients treated with definitive and adjuvant radiotherapy for squamous cell carcinomas of the nasal cavity and paranasal sinuses in a single institution. METHODS: Between 2007-2012 patients were retrospectively identified from electronic databases who had undergone surgery and adjuvant radiotherapy or definitive radiotherapy for sinonasal squamous cell carcinomas with curative intent. RESULTS: Fourty three patients with sinonasal squamous cell carcinoma were identified (22 nasal cavity, 21 paranasal sinuses). 31/43 (72%) had T3 or T4 disease; nodal stage was N0 in 38, N1 in 4, Na/b in 0 and N2c in 1 patient. Median age was 67 years (range 41-86). 18 (42%) received definitive and 25 (58%) adjuvant radiotherapy. Radiotherapy was delivered using either conventional radiotherapy (n = 39) or intensity modulated radiotherapy (n = 4). Elective neck radiotherapy was delivered to two patients. Chemotherapy was delivered to 6/43 (14%) of patients. Two-year local control, regional control, distant metastases free survival, progression free survival, cause specific survival and overall survival were 81%, 90%, 95%, 71%, 84% and 80% respectively. There was no significant difference in outcome comparing patients who underwent surgery and adjuvant radiotherapy with patients receiving definitive radiotherapy (2 year locoregional disease free survival 75% and 70% respectively, p = 0.98). Pooly differentiated tumours were significantly associated with inferior disease outcomes. Local, regional, combined local and regional, and distant failure occurred in 7 (16%), 3 (7%), 1 (2%) and 2 (5%) of patients; all 3 regional recurrences were in patients with nasal cavity squamous cell carcinomas who had not undergone elective neck treatment. CONCLUSIONS: Definitive or adjuvant radiotherapy provides an effective treatment for sinonasal malignancies. The main pattern of failure remains local, suggesting the need for investigation of intensified local therapy. Whilst remaining uncommon, the cases of regional failure mean that the merits of elective lymph node treatment should be considered on an individual basis. PMID- 26377410 TI - Branched-chain amino acids for people with hepatic encephalopathy. AB - BACKGROUND: Hepatic encephalopathy is a brain dysfunction with neurological and psychiatric changes associated with liver insufficiency or portal-systemic shunting. The severity ranges from minor symptoms to coma. A Cochrane systematic review including 11 randomised clinical trials on branched-chain amino acids (BCAA) versus control interventions has evaluated if BCAA may benefit people with hepatic encephalopathy. OBJECTIVES: To evaluate the beneficial and harmful effects of BCAA versus any control intervention for people with hepatic encephalopathy. SEARCH METHODS: We identified trials through manual and electronic searches in The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and Science Citation Index (August 2015). SELECTION CRITERIA: We included randomised clinical trials, irrespective of the bias control, language, or publication status. DATA COLLECTION AND ANALYSIS: The authors independently extracted data based on published reports and collected data from the primary investigators. We changed our primary outcomes in this update of the review to include mortality (all cause), hepatic encephalopathy (number of people without improved manifestations of hepatic encephalopathy), and adverse events. The analyses included random-effects and fixed-effect meta-analyses. We performed subgroup, sensitivity, regression, and trial sequential analyses to evaluate sources of heterogeneity (including intervention, and participant and trial characteristics), bias (using The Cochrane Hepato-Biliary Group method), small study effects, and the robustness of the results after adjusting for sparse data and multiplicity. We graded the quality of the evidence using the GRADE approach. MAIN RESULTS: We found 16 randomised clinical trials including 827 participants with hepatic encephalopathy classed as overt (12 trials) or minimal (four trials). Eight trials assessed oral BCAA supplements and seven trials assessed intravenous BCAA. The control groups received placebo/no intervention (two trials), diets (10 trials), lactulose (two trials), or neomycin (two trials). In 15 trials, all participants had cirrhosis. We classed seven trials as low risk of bias and nine trials as high risk of bias (mainly due to lack of blinding or for profit funding). In a random-effects meta-analysis of mortality, we found no difference between BCAA and controls (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.69 to 1.11; 760 participants; 15 trials; moderate quality of evidence). We found no evidence of small-study effects. Sensitivity analyses of trials with a low risk of bias found no beneficial or detrimental effect of BCAA on mortality. Trial sequential analysis showed that the required information size was not reached, suggesting that additional evidence was needed. BCAA had a beneficial effect on hepatic encephalopathy (RR 0.73, 95% CI 0.61 to 0.88; 827 participants; 16 trials; high quality of evidence). We found no small-study effects and confirmed the beneficial effect of BCAA in a sensitivity analysis that only included trials with a low risk of bias (RR 0.71, 95% CI 0.52 to 0.96). The trial sequential analysis showed that firm evidence was reached. In a fixed effect meta-analysis, we found that BCAA increased the risk of nausea and vomiting (RR 5.56; 2.93 to 10.55; moderate quality of evidence). We found no beneficial or detrimental effects of BCAA on nausea or vomiting in a random effects meta-analysis or on quality of life or nutritional parameters. We did not identify predictors of the intervention effect in the subgroup, sensitivity, or meta-regression analyses. In sensitivity analyses that excluded trials with a lactulose or neomycin control, BCAA had a beneficial effect on hepatic encephalopathy (RR 0.76, 95% CI 0.63 to 0.92). Additional sensitivity analyses found no difference between BCAA and lactulose or neomycin (RR 0.66, 95% CI 0.34 to 1.30). AUTHORS' CONCLUSIONS: In this updated review, we included five additional trials. The analyses showed that BCAA had a beneficial effect on hepatic encephalopathy. We found no effect on mortality, quality of life, or nutritional parameters, but we need additional trials to evaluate these outcomes. Likewise, we need additional randomised clinical trials to determine the effect of BCAA compared with interventions such as non-absorbable disaccharides, rifaximin, or other antibiotics. PMID- 26377411 TI - Deferral of surgery for epiretinal membranes: Is it safe? Results of a randomised controlled trial. AB - BACKGROUND/AIMS: To compare the visual outcome in early versus deferred surgery in patients with idiopathic epiretinal membrane (ERM) and good presenting visual acuity and mild symptoms. METHODS: This study is a randomised clinical trial. 53 eyes of 53 patients with symptomatic ERM and best-corrected visual acuity (BCVA) at presentation >=65 early treatment diabetic retinopathy study (ETDRS) letters were randomised to immediate surgery (20 eyes) or to watchful waiting (33 eyes) for 1 year. Primary end-point was BCVA after 12 months. Secondary end-points were central macular thickness and the number of patients that crossed over from the watchful waiting arm to the surgery arm due to deteriorated symptoms. RESULTS: Mean BCVA after 12 months in the watchful waiting group (81 letters) were not significantly different from patients undergoing immediate surgery (82.5 letters, p=0.647). During 1 year of follow-up, eight patients in the watchful waiting group (24%) crossed over to surgery and these patients gained a mean of 3.1 letters (SEM 1.38). Patients randomised to immediate surgery gained approximately one line. Watchful waiting patients who remained without surgery were stable. The visual acuity gain after surgery is slow and gradual until 9 months postoperatively. There were no serious complications such as retinal detachment or infectious endophthalmitis. CONCLUSIONS: Vitrectomy for early symptomatic ERM is beneficial in preserving excellent vision. A watchful waiting approach with 1 year of follow-up is safe in the sense that this group does not lose five ETDRS letters in waiting. Deferral of surgery by regular monitoring of patients is a safe approach. TRIAL REGISTRATION NUMBERS: H-C-2008-026 and NCT00902629. PMID- 26377412 TI - Impression membrane for the diagnosis of microbial keratitis. AB - PURPOSE: To evaluate a corneal impression membrane (CIM) for isolation of bacteria, fungi and acanthamoeba in suspected microbial keratitis. METHODS: Consecutive patients presenting with suspected microbial keratitis were included. For each patient, samples were collected in a random order using a surgical blade and a 4-mm-diameter polytetrafluoroethylene CIM disc, and transported in brain heart infusion broth. Risk factors, best corrected visual acuity (BCVA), size, location, depth and healing time of the ulcer were recorded. The microbial isolation rate was used to compare sampling methods. RESULTS: 130 patients were included (mean age 62.6 years, SD 19.0). An antimicrobial had been used prior to presentation in 36 (27.7%) patients. Mean major and minor ulcer diameters were 2.1 mm (SD 2.0) and 1.6 mm (SD 1.7). Mean healing time was 12.4 days (SD 13.6). BCVA at presentation and following healing was 0.7 (SD 0.7) and 0.62 (SD 0.7) (p=0.34). There were 66 isolates (50.8%); 53 (40.8%) using a CIM and 35 (26.9%) using a blade (p=0.02). ITALIC! Staphylococcus aureus and coagulase-negative staphylococci were the commonest isolates. Isolation rate was not influenced by organism type, although in four cases ITALIC! Acanthamoeba spp. were isolated; three using CIM and one a blade. CONCLUSIONS: In this study, the isolation of microorganisms from cases of suspected microbial keratitis was significantly higher using a CIM than a surgical blade. A CIM may be a useful alternative or addition for sample collection in microbial keratitis. PMID- 26377409 TI - A scoping review of rapid review methods. AB - BACKGROUND: Rapid reviews are a form of knowledge synthesis in which components of the systematic review process are simplified or omitted to produce information in a timely manner. Although numerous centers are conducting rapid reviews internationally, few studies have examined the methodological characteristics of rapid reviews. We aimed to examine articles, books, and reports that evaluated, compared, used or described rapid reviews or methods through a scoping review. METHODS: MEDLINE, EMBASE, the Cochrane Library, internet websites of rapid review producers, and reference lists were searched to identify articles for inclusion. Two reviewers independently screened literature search results and abstracted data from included studies. Descriptive analysis was conducted. RESULTS: We included 100 articles plus one companion report that were published between 1997 and 2013. The studies were categorized as 84 application papers, seven development papers, six impact papers, and four comparison papers (one was included in two categories). The rapid reviews were conducted between 1 and 12 months, predominantly in Europe (58 %) and North America (20 %). The included studies failed to report 6 % to 73 % of the specific systematic review steps examined. Fifty unique rapid review methods were identified; 16 methods occurred more than once. Streamlined methods that were used in the 82 rapid reviews included limiting the literature search to published literature (24 %) or one database (2 %), limiting inclusion criteria by date (68 %) or language (49 %), having one person screen and another verify or screen excluded studies (6 %), having one person abstract data and another verify (23 %), not conducting risk of bias/quality appraisal (7 %) or having only one reviewer conduct the quality appraisal (7 %), and presenting results as a narrative summary (78 %). Four case studies were identified that compared the results of rapid reviews to systematic reviews. Three studies found that the conclusions between rapid reviews and systematic reviews were congruent. CONCLUSIONS: Numerous rapid review approaches were identified and few were used consistently in the literature. Poor quality of reporting was observed. A prospective study comparing the results from rapid reviews to those obtained through systematic reviews is warranted. PMID- 26377413 TI - Individualised risk assessment for diabetic retinopathy and optimisation of screening intervals: a scientific approach to reducing healthcare costs. AB - OBJECTIVE: To validate a mathematical algorithm that calculates risk of diabetic retinopathy progression in a diabetic population with UK staging (R0-3; M1) of diabetic retinopathy. To establish the utility of the algorithm to reduce screening frequency in this cohort, while maintaining safety standards. RESEARCH DESIGN AND METHODS: The cohort of 9690 diabetic individuals in England, followed for 2 years. The algorithms calculated individual risk for development of preproliferative retinopathy (R2), active proliferative retinopathy (R3A) and diabetic maculopathy (M1) based on clinical data. Screening intervals were determined such that the increase in risk of developing certain stages of retinopathy between screenings was the same for all patients and identical to mean risk in fixed annual screening. Receiver operating characteristic curves were drawn and area under the curve calculated to estimate the prediction capability. RESULTS: The algorithm predicts the occurrence of the given diabetic retinopathy stages with area under the curve =80% for patients with type II diabetes (CI 0.78 to 0.81). Of the cohort 64% is at less than 5% risk of progression to R2, R3A or M1 within 2 years. By applying a 2 year ceiling to the screening interval, patients with type II diabetes are screened on average every 20 months, which is a 40% reduction in frequency compared with annual screening. CONCLUSIONS: The algorithm reliably identifies patients at high risk of developing advanced stages of diabetic retinopathy, including preproliferative R2, active proliferative R3A and maculopathy M1. Majority of patients have less than 5% risk of progression between stages within a year and a small high-risk group is identified. Screening visit frequency and presumably costs in a diabetic retinopathy screening system can be reduced by 40% by using a 2 year ceiling. Individualised risk assessment with 2 year ceiling on screening intervals may be a pragmatic next step in diabetic retinopathy screening in UK, in that safety is maximised and cost reduced by about 40%. PMID- 26377414 TI - Reproducibility and repeatability of foveal avascular zone measurements in healthy subjects by optical coherence tomography angiography. AB - BACKGROUND/AIMS: To assess the reproducibility and repeatability of foveal avascular zone (FAZ) area measurements using optical coherence tomography angiography (OCT-A) in healthy subjects. METHODS: Sixty healthy volunteers (60 eyes) were subjected to FAZ area measurements by means of high speed and high resolution spectral-domain OCT (SD-OCT) XR Avanti with the split-spectrum amplitude decorrelation angiography algorithm by two experienced examiners in two different sessions. RESULTS: The mean+/-SD age of the subjects was 28.9+/-7.6 years. Overall FAZ areas measured by the first and second observer were 0.251+/ 0.096 mm(2) and 0.252+/-0.096 mm(2), respectively. Within subjects, the coefficients of variations were 1.83% (95% CI 1.51% to 2.20%) and 1.86% (95% CI 1.33% to 2.43%) for the first and second observers, respectively. The coefficient of repeatability average measurements of FAZ area were 0.015 mm(2) and 0.013 mm(2) for the first and second observers, respectively. The intraclass correlation coefficient values were 0.997 (95% CI 0.995 to 0.998) and 0.998 (95% CI 0.996 to 0.999) for the first and second observers, respectively. Inter- and intraobserver concordance correlation coefficients ranged from 0.994 (95% CI 0.990 to 0.977) to 0.999 (95% CI 0.997 to 0.999) and from 0.997 (95% CI 0.995 to 0.998) to 0.996 (95% CI 0.994 to 0.998), respectively. CONCLUSIONS: FAZ area measurements by means of OCT-A showed excellent reproducibility and repeatability in healthy eyes. OCT-A is a non-invasive diagnostic method, and its reliability makes it an interesting potential diagnostic tool for disease detection and follow-up in retinal pathologies involving foveal microcirculation. PMID- 26377415 TI - Effect of the pigment-free optical zone diameter of decorative tinted soft contact lenses on visual function. AB - AIMS: We investigated changes in visual function after wearing decorative tinted soft contact lenses with different pigment-free optical zone diameters. METHODS: A prospective study was performed in 30 eyes of 30 healthy volunteers. Best corrected visual acuity (BCVA), ocular higher-order aberrations (HOAs), modulation transfer function (MTF), Strehl ratio and contrast sensitivity were evaluated after wearing clear lens and tinted lenses with different pigment-free optical zone diameters (4, 5 and 6 mm). RESULTS: BCVA decreased from 0.00 logMAR after wearing a clear lens to 0.04+/-0.04 logMAR after wearing 4 mm optical zone lens (p<0.001). As the optical zone diameter decreased, ocular aberrations were induced. Total HOAs, coma aberration and secondary astigmatism showed significant difference between clear lens and 5 or 4 mm optical zone lenses (p<0.050). Spherical aberration and trefoil showed significant difference between clear lens and 4 mm optical zone lens (p<0.050). The results for Strehl ratio revealed poorer optical quality for both 5 and 4 mm optical zone lens (both p=0.002). The entire ocular MTF was significantly different, corresponding to the decreased optical zone diameter. The HOAs showed a correlation with the blocked pupil covered by the tinted part (r=0.435, p<0.001). In photopic and mesopic conditions, the contrast sensitivity decreased significantly with the reduced pigment-free optical zone diameters. CONCLUSION: Decorative tinted contact lenses significantly increased ocular aberrations and decreased optical quality and contrast sensitivity, as the pigment-free optical zone diameter decreased. Therefore, consumers of tinted lenses should be informed about the possible disturbance in visual function. TRIAL REGISTRATION NUMBER: NCT02537275. PMID- 26377416 TI - Incomplete response to artificial tears is associated with features of neuropathic ocular pain. AB - AIMS: Artificial tears are first-line therapy for patients with dry eye symptoms. It is not known, however, which patient factors associate with a positive response to therapy. The purpose of this study was to evaluate whether certain ocular and systemic findings are associated with a differential subjective response to artificial tears. METHODS: Cross-sectional study of 118 individuals reporting artificial tears use (hypromellose 0.4%) to treat dry eye-associated ocular pain. An evaluation was performed to assess dry eye symptoms (via the dry eye questionnaire 5 and ocular surface disease index), ocular and systemic (non ocular) pain complaints and ocular signs (tear osmolarity, tear breakup time, corneal staining, Schirmer testing with anaesthesia, and eyelid and meibomian gland assessment). The main outcome measures were factors associated with differential subjective response to artificial tears. RESULTS: By self-report, 23 patients reported no improvement, 73 partial improvement and 22 complete improvement in ocular pain with artificial tears. Patients who reported no or partial improvement in pain with artificial tears reported higher levels of hot burning ocular pain and sensitivity to wind compared with those with complete improvement. Patients were also asked to rate the intensity of systemic pain elsewhere in the body (other than the eye). Patients who reported no or incomplete improvement with artificial tears had higher systemic pain scores compared with those with complete improvement. CONCLUSIONS: Both ocular and systemic (non-ocular) pain complaints are associated with a differential subjective response to artificial tears. PMID- 26377417 TI - Developments in laser trabeculoplasty. AB - Laser trabeculoplasty has an increasing important role in the management of glaucoma as more emphasis is placed on minimally invasive therapies. In recent years, the following laser trabeculoplasty technologies have been introduced: micropulse laser trabeculoplasty, titanium-sapphire laser trabeculoplasty and pattern scanning trabeculoplasty. These lasers help to reduce the intraocular pressure (IOP) and the burden of glaucoma medical therapy. Literature findings regarding the safety and efficacy of these newer forms of laser trabeculoplasty in the treatment of open-angle glaucoma is summarised. These relatively newer procedures appear to have similar efficacy when compared with the former selective laser trabeculoplasty or argon laser trabeculoplasty. In addition, they potentially offer a more favourable safety profile with fewer complications, including postlaser inflammation and IOP spikes. Further large-scale studies are necessary to evaluate the long-term benefits of these newer forms of laser trabeculoplasty. Their initial promising results offer patients with glaucoma additional treatment alternatives. PMID- 26377419 TI - The Racial School Climate Gap: Within-School Disparities in Students' Experiences of Safety, Support, and Connectedness. AB - This study used student and teacher survey data from over 400 middle schools in California to examine within-school racial disparities in students' experiences of school climate. It further examined the relationship between a school's racial climate gaps and achievement gaps and other school structures and norms that may help explain why some schools have larger or smaller racial disparities in student reports of climate than others. Multilevel regression results problematized the concept of a "school climate" by showing that, in an average middle school, Black and Hispanic students have less favorable experiences of safety, connectedness, relationships with adults, and opportunities for participation compared to White students. The results also show that certain racial school climate gaps vary in magnitude across middle schools, and in middle schools where these gaps are larger, the racial achievement gap is also larger. Finally, the socioeconomic status of students, student-teacher ratio, and geographic location help explain some cross-school variation in racial climate gaps. These findings have implications for how school climate in conceptualized, measured, and improved. PMID- 26377418 TI - Effects of Communities That Care on Males' and Females' Drug Use and Delinquency 9 Years After Baseline in a Community-Randomized Trial. AB - This study tested sustained effects of the Communities That Care (CTC) prevention system on health-risking behaviors 9 years after baseline in a community randomized trial involving 24 towns in seven states. Earlier analyses found sustained effects on abstinence from drug use and delinquency through Grade 12 in a panel of fifth graders. At age 19, 91 % (n = 3986) of the living panel completed the survey. Data were analyzed using generalized linear mixed models. The prevalence of lifetime and current substance use and delinquency were the primary outcomes. Secondary outcomes included substance use disorders, major depression, suicidality, educational attainment, and sexual risk behaviors. CTC had a significant overall effect across lifetime measures of the primary outcomes for males, but not for females or the full sample, although lifetime abstinence from delinquency in the full sample was significantly higher in CTC communities (ARR = 1.16). Males in CTC communities also continued to show greater lifetime abstinence from cigarette smoking (ARR = 1.22). CTC did not have a sustained effect on current substance use and delinquency nor did it improve the secondary outcomes at age 19 for either gender. Communities using CTC may need to extend their prevention planning to include the high school years to sustain effects on drug use and delinquency beyond high school for both genders. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01088542. PMID- 26377421 TI - Characterization of monoclonal antibodies that recognize the amino- and carboxy terminal epitopes of the pseudorabies virus UL42 protein. AB - The pseudorabies virus (PRV) UL42 protein, known as the DNA polymerase processivity factor, is an essential protein required for viral replication. The in vitro function of UL42 has been characterized; however, there is little information concerning the linear B cell epitopes of UL42 that are recognized during humoral immune responses. We generated and characterized six UL42-reactive monoclonal antibodies (mAbs) from mice that had been immunized with a recombinant form of UL42. Through western blotting analysis, we identified two regions of UL42 (amino acids 39-148 and 302-384) that reacted with these mAbs. We then synthesized a panel of UL42-derived peptides spanning the two regions and screened the six mAbs. We were able to identify three linear epitopes ((116)SGGVLDALK(124), (354)KRPAAPR(360), and (360)RMYTPIAK(367)) by enzyme-linked immunosorbent assays. The (116)SGGVLDALK(124) epitope was located at the amino terminus, while the other two epitopes were at the carboxy-terminus. Using these mAbs, we found that UL42 localized to the nucleus during viral replication and could be immunoprecipitated from PRV-infected PK-15 cells. We also established a UL42 mAb-based immunoperoxidase monolayer assay for the determination of PRV titers. Sequence analysis showed that the linear epitopes of UL42 were highly conserved among PRV strains. Taken together, our results indicate that the six generated mAbs could be useful tools for investigating the structure and function of UL42 during viral replication. In addition, these mAbs could be applied to diagnostic and therapeutic approaches for the effective control of PRV infections. PMID- 26377420 TI - Association of serum lipid levels and prostate cancer severity among Hispanic Puerto Rican men. AB - BACKGROUND: While obesity and fat intake have been associated with an increased risk of prostate cancer (PCa) aggressiveness and mortality, the association between lipid levels and PCa phenotype remains unclear. Previous reports evaluating this association are inconsistent and highly variable when considering different racial/ethnic groups. There are scarce data regarding this association among Hispanics, and specifically Puerto Rico's Hispanic men, a population with a higher burden of PCa, metabolic syndrome and overweight. This population has a different ancestry profile than other Hispanics from Central and South America. Due to the above the researchers inquired if there is a relationship between serum lipid levels and PCa phenotype in this understudied population using a cohort of patients treated with radical prostatectomy as their first treatment. METHODS: We performed an exploratory retrospective medical record review study of 199 PCa patients who underwent radical prostatectomy between 2005 and 2012. Variables analyzed included age at PCa diagnosis, Body Mass Index (BMI), preoperative serum prostate-specific antigen (PSA), lipid levels, and clinical parameters such as prostatectomy pathologic stage and Gleason Score (GS). PCa severity was defined using pathologic stage and GS. Unadjusted and adjusted logistic regression models were fitted to estimate the odds ratios (ORs) with 95 % confidence intervals (CI) to define the relationship among clinical characteristics and PCa severity. RESULTS: Mean age for the cohort was 58.8 years (range: 40-75), 78.9 % were overweight or obese, 36.7 % had hypertriglyceridemia, and 35.2 % had low HDL levels. In the unadjusted logistic regression model, hypertriglyceridemia (OR: 2.11, 95 % CI = 1.13-3.93), low HDL (OR: 1.90, 95 % CI = 1.02-3.56-), and age (OR: 2.34, 95 % CI 1.25-4.40) were significantly associated with a diagnosis of high severity of PCa. CONCLUSIONS: In Puerto Rican men with PCa, elevated hypertriglyceridemia, low HDL levels, and age were statistically associated with high grade PCa on bivariate analysis. Total cholesterol level was not associated with severity of disease. Associations lost significance upon multivariate adjustment. These data generate important hypotheses regarding the potential relationship between lipid pathways and PCa development and underscore the need to perform larger scale and longitudinal studies to sort out whether, hypertriglyceridemia is associated with PCa phenotype and development. PMID- 26377422 TI - Stereoselective reduction of aromatic ketones by a new ketoreductase from Pichia glucozyma. AB - A new NADPH-dependent benzil reductase (KRED1-Pglu) was identified from the genome of the non-conventional yeast Pichia glucozyma CBS 5766 and overexpressed in E. coli. The new protein was characterised and reaction parameters were optimised for the enantioselective reduction of benzil to (S)-benzoin. A thorough study of the substrate range of KRED1-Pglu was conducted; in contrast to most other known ketoreductases, KRED1-Pglu prefers space-demanding substrates, which are often converted with high stereoselectivity. A molecular modelling study was carried out for understanding the structural determinants involved in the stereorecognition experimentally observed and unpredictable on the basis of steric properties of the substrates. As a result, a new useful catalyst was identified, enabling the enantioselective preparation of different aromatic alcohols and hydroxyketones. PMID- 26377423 TI - Surveillance for the safety and effectiveness of artemether-lumefantrine in patients with uncomplicated Plasmodium falciparum malaria in the USA: a descriptive analysis. AB - BACKGROUND: Data from clinical studies show that artemether-lumefantrine (AL) is effective and well tolerated in adults and children with uncomplicated Plasmodium falciparum malaria. However, data on effectiveness and safety of AL in patients in non-endemic settings are limited. METHODS: A 5-year surveillance plan included all AL-treated adult and paediatric patients with confirmed or suspected P. falciparum malaria in the USA, as reported to the National Malaria Surveillance System at the Centers for Disease Control and Prevention. Descriptive analyses included demographics, baseline characteristics, clinical effectiveness, and safety. From May 2010 to April 2015, demographics and baseline characteristics were collected for 203 patients and safety data for 108 patients. Treatment effectiveness data at day 7 were collected for 117 patients and at day 28 for 98 patients. RESULTS: The majority of patients were male (58.6 %), Black (62.6 %), non-Hispanic (92.6 %), and likely malaria non-immune (80.8 %). The median age was 32 (range 1-88) years and the median body mass index was 25.5 (range 13.8-42.4) kg/m(2). All patients with effectiveness data had confirmed (n = 116) or suspected (n = 1) malaria. The overall cure rate for patients treated with AL was 91.5 % (95 % CI 84.8-95.8 %) at day 7 and 96.9 % (95 % CI 91.3-99.4 %) at day 28. Adverse events were reported in four (3.7 %) patients, and there were no new or unexpected safety signals. CONCLUSION: AL was effective and well tolerated in the treatment of likely non-immune patients with P. falciparum malaria. PMID- 26377424 TI - Erratum to: Alendronate sodium/vitamin D3 combination tablet versus calcitriol for osteoporosis in Chinese postmenopausal women: a 6-month, randomized, open label, active-comparator-controlled study with a 6-month extension. PMID- 26377425 TI - The top 100 articles in the radiology of trauma: a bibliometric analysis. AB - The purpose of this study was to identify the 100 top-cited articles in the radiology of trauma, analyze the resulting database to understand factors resulting in highly cited works, and establish trends in trauma imaging. An initial database was created via a Web of Science (WOS) search of all scientific journals using the search terms "trauma" and either "radiology" or a diagnostic modality. Articles were ranked by citation count and screened by two attending radiologists plus a tiebreaker for appropriateness. The following information was collected from each article: WOS all database citations, year, journal, authors, department affiliation, study type and design, sample size, imaging modality, subspecialty, organ, and topic. Citations for the top 100 articles ranged from 82 252, and citations per year ranged from 2.6-37.2. A plurality of articles were published in the 1990s (n = 45) and 1980s (n = 31). Articles were published across 24 journals, most commonly Radiology (n = 31) and Journal of Trauma Injury, Infection, and Critical Care (n = 28). Articles had an average of five authors and 35 % of first authors were affiliated with a department other than radiology. Forty-six articles had sample sizes of 100 or fewer. Computed tomography (CT) was the most common modality (n = 67), followed by magnetic resonance (MR; n = 22), and X-ray (XR; n = 11). Neuroradiology (n = 48) and abdominal radiology (n = 36) were the most common subspecialties. The 100 top cited articles in the radiology of trauma are diverse. Subspecialty bibliometric analyses identify the most influential articles of a particular field, providing more implications to clinical radiologists, trainees, researchers, editors, and reviewers than radiology-wide lists. PMID- 26377426 TI - The Establishment and Utility of a Free Online Database of Primary Bone Tumors. PMID- 26377427 TI - Reduced acquisition times in whole body bone scintigraphy using a noise-reducing Pixon(r)-algorithm-a qualitative evaluation study. AB - BACKGROUND: Reducing scan-time while maintaining sufficient image quality is a common issue in nuclear medicine diagnostics. This matter can be addressed by different post-processing methods such as Pixon(r) image processing. The aim of the present study was to evaluate if a commercially available noise-reducing Pixon-algorithm applied on whole body bone scintigraphy acquired with half the standard scan-time could provide the same clinical information as full scan-time non-processed images. METHODS: Twenty patients were administered with 500 MBq (99m)Tc-diphosphonate and scanned on a Siemens Symbia T16 system. Each patient was first imaged using a standard clinical protocol and subsequently imaged using a protocol with half the standard scan-time. Half-time images were processed using a commercially available software package, Enhanced Planar Processing, from Siemens. All images were anonymized and visually evaluated with regard to clinically relevant lesion detectability by three experienced nuclear medicine physicians. The result of this evaluation was grouped into four BMI intervals to investigate the performance of the algorithm with regard to different patient size. Also, a comparison study was performed where the physicians compared the standard image and the processed half-time image corresponding to the same patient with regard to lesion detectability, image noise, and artifacts. RESULTS: The results showed that 93 % of the processed half-time images and 98 % of the standard images were rated as sufficient or good with regard to lesion detectability. The processed half-time images were predominately considered sufficient (65 %), whereas the majority of the standard images were graded as good (83 %). The performance of the algorithm was unaffected by patient size as the average grading of all half-time processed images was constant independent of patient BMI. The comparison study showed that the standard images were rated superior with regard to lesion detectability, image noise, and artifacts, in 32, 65, and 23 % of the evaluations, respectively. CONCLUSIONS: The results indicate that the Pixon Enhanced Planar Processing does not fully compensate for the loss of counts associated with reducing the scan-time in half for whole body bone scintigraphies. The findings showed that implementing the Pixon-algorithm on images acquired with half the acquisition time in overall provide sufficient clinical information regardless of patient size. The half-time processed images were predominantly graded lower in comparison to images acquired with full time protocols, and a less aggressive reduction in scan-time is therefore recommended. PMID- 26377428 TI - Studies on the formation and stability of triplex DNA using fluorescence correlation spectroscopy. AB - Triplex DNA has become one of the most useful recognition motifs in the design of new molecular biology tools, therapeutic agents and sophisticated DNA-based nanomaterials because of its direct recognition of natural double-stranded DNA. In this paper, we developed a sensitive and microscale method to study the formation and stability characterization of triplex DNA using fluorescence correlation spectroscopy (FCS). The principle of this method is mainly based on the excellent capacity of FCS for sensitively distinguishing between free single strand DNA (ssDNA) fluorescent probes and fluorescent probe-double-strand DNA (dsDNA) hybridized complexes. First, we systematically investigated the experimental conditions of triplex DNA formation. Then, we evaluated the equilibrium association constants (K(a)) under different ssDNA probe lengths, composition and pH. Finally, we used FCS to measure the hybridization fraction of a 20-mer perfectly matched ssDNA probe and three single-base mismatched ssDNA probes with 146-mer dsDNA. Our data illustrated that FCS is a useful tool for the direct determination of the thermodynamic parameters of triplex DNA formation and discrimination of a single-base mismatch of triplex DNA without denaturation. Compared with current methods, our method is characterized by high sensitivity, good universality and small sample and reagent requirements. More importantly, our method has the potential to become a platform for triplex DNA research in vitro. PMID- 26377429 TI - Transcatheter mitral valve repair with the MitraClip((r)) can be performed without general anesthesia and without conscious sedation. AB - BACKGROUND: General anesthesia is known to be associated with an increased risk for complications, especially in elderly and multi-morbid patients, the primary target population of the MitraClip((r)) technique. The aim is to assess whether general anesthesia and even conscious sedation can be avoided during the MitraClip((r)) procedure. METHODS: A total of 91 consecutive patients who underwent MitraClip((r)) implantation [median 77 years, (IQR 72-83), 40 % female] were retrospectively analyzed. The first 26 patients were treated in general anesthesia. Afterwards, local anesthesia was chosen as primary anesthetic approach. Altogether, 28 (31 %) patients received general anesthesia, local anesthesia was performed in 35 (38 %) patients with sedation and in 28 (31 %) patients without sedation. RESULTS: The respective patient groups were similar regarding their baseline characteristics. Procedural success (successful implantation of at least one clip and post-procedure MR grade <=2) was achieved in 89 % with no difference between the groups (93 % in general anesthesia, 89 % in local anesthesia with sedation, 86 % in local anesthesia without sedation, p = ns). No difference regarding hospital complications was noted. Local anesthesia with and without sedation was associated with less necessity for ICU/IMC stay (100 % in general anesthesia, 14 % in local anesthesia with sedation, 14 % in local anesthesia without sedation; p < 0.0001). One-year estimated survival was not significantly different among the groups (63, 82 and 75 %; p = ns). CONCLUSIONS: Transcatheter mitral valve repair with the MitraClip((r)) can be performed without general anesthesia and even without conscious sedation with similar procedural success and complication rates. PMID- 26377430 TI - Cardiopulmonary exercise testing is predictive of return to work in cardiac patients after multicomponent rehabilitation. AB - BACKGROUND: Return to work (RTW) is a pivotal goal of cardiac rehabilitation (CR) in patients after acute cardiac event. We aimed to evaluate cardiopulmonary exercise testing (CPX) parameters as predictors for RTW at discharge after CR. METHODS: We analyzed data from a registry of 489 working-age patients (51.5 +/- 6.9 years, 87.9 % men) who had undergone inpatient CR predominantly after percutaneous coronary intervention (PCI 62.6 %), coronary artery bypass graft (CABG 17.2 %), or heart valve replacement (9.0 %). Sociodemographic and clinical parameters, noninvasive cardiac diagnostic (2D echo, exercise ECG, 6MWT) and psychodiagnostic screening data, as well as CPX findings, were merged with RTW data from the German statutory pension insurance program and analyzed for prognostic ability. RESULTS: During a mean follow-up of 26.5 +/- 11.9 months, 373 (76.3 %) patients returned to work, 116 (23.7 %) did not, and 60 (12.3 %) retired. After adjustment for covariates, elective CABG (HR 0.68, 95 % CI 0.47 0.98; p = 0.036) and work intensity (per level HR 0.83, 95 % CI 0.73-0.93; p = 0.002) were negatively associated with the probability of RTW. Exercise capacity in CPX (in Watts) and the VE/VCO2-slope had independent prognostic significance for RTW. A higher work load increased (HR 1.17, 95 % CI 1.02-1.35; p = 0.028) the probability of RTW, while a higher VE/VCO2 slope decreased (HR 0.85, 95 % CI 0.76 0.96; p = 0.009) it. CPX also had prognostic value for retirement: the likelihood of retirement decreased with increasing exercise capacity (HR 0.50, 95 % CI 0.30 0.82; p = 0.006). CONCLUSION: CPX is a valid tool for assessing patients' ability to return to work. Therefore, it may be an essential part of functional assessment during CR for predicting participation in employment. PMID- 26377431 TI - Adenovirus disease in six small bowel, kidney and heart transplant recipients; pathology and clinical outcome. AB - Adenoviruses are emerging as important viral pathogens in hematopoietic stem cell and solid organ transplant recipients, impacting morbidity, graft survival, and even mortality. The risk seems to be highest in allogeneic hematopoietic stem cell transplant recipients as well as heart, lung, and small bowel transplant recipients. Most of the adenovirus diseases develop in the first 6 months after transplantation, particularly in pediatric patients. Among abdominal organ recipients, small bowel grafts are most frequently affected, presumably due to the presence of a virus reservoir in the mucosa-associated lymphoid tissue. Management of these infections may be difficult and includes the reduction of immunosuppression, whenever possible, combined with antiviral therapy, if necessary. Therefore, an awareness of the pathology associated with such infections is important in order to allow early detection and specific treatment. We reviewed six transplant recipients (small bowel, kidney, and heart) with adenovirus graft involvement from two institutions. We sought to compare the diagnostic morphology and the clinical and laboratory findings. The histopathologic features of an adenovirus infection of the renal graft and one native kidney in a heart transplant recipient included a vaguely granulomatous mixed inflammatory infiltrate associated with rare cells showing a cytopathic effect (smudgy nuclei). A lymphocytic infiltrate, simulating T cell rejection, with admixture of eosinophils was also seen. In the small bowel grafts, there was a focal mixed inflammatory infiltrate with associated necrosis in addition to cytopathic effects. In the heart, allograft adenovirus infection was silent with no evidence of inflammatory changes. Immunohistochemical stain for adenovirus was positive in all grafts and in one native kidney. All patients were subsequently cleared of adenovirus infection, as evidenced by follow-up biopsies, with no loss of the grafts. Adenovirus infection can involve allografts as well as native organs in solid organ transplant recipients. Infection is associated with variable necrosis and acute inflammation, in addition to a rejection-like infiltrate. Hematuria in non-renal solid organ transplant recipients may be associated with adenovirus nephritis and clinically silent graft involvement. Prompt diagnosis (aided by immunohistochemistry (IHC) and serology), with specific treatment, can prevent graft loss. PMID- 26377432 TI - Sex-linked genomic variation and its relationship to avian plumage dichromatism and sexual selection. AB - BACKGROUND: Sexual dichromatism is the tendency for sexes to differ in color pattern and represents a striking form of within-species morphological variation. Conspicuous intersexual differences in avian plumage are generally thought to result from Darwinian sexual selection, to the extent that dichromatism is often treated as a surrogate for the intensity of sexual selection in phylogenetic comparative studies. Intense sexual selection is predicted to leave a footprint on genetic evolution by reducing the relative genetic diversity on sex chromosome to that on the autosomes. RESULTS: In this study, we test the association between plumage dichromatism and sex-linked genetic diversity using eight species pairs with contrasting levels of dichromatism. We estimated Z-linked and autosomal genetic diversity for these non-model avian species using restriction-site associated (RAD) loci that covered ~3 % of the genome. We find that monochromatic birds consistently have reduced sex-linked genomic variation relative to phylogenetically-paired dichromatic species and this pattern is robust to mutational biases. CONCLUSIONS: Our results are consistent with several interpretations. If present-day sexual selection is stronger in dichromatic birds, our results suggest that its impact on sex-linked genomic variation is offset by other processes that lead to proportionately lower Z-linked variation in monochromatic species. We discuss possible factors that may contribute to this discrepancy between phenotypes and genomic variation. Conversely, it is possible that present-day sexual selection -- as measured by the variance in male reproductive success -- is stronger in the set of monochromatic taxa we have examined, potentially reflecting the importance of song, behavior and other non plumage associated traits as targets of sexual selection. This counterintuitive finding suggests that the relationship between genomic variation and sexual selection is complex and highlights the need for a more comprehensive survey of genomic variation in avian taxa that vary markedly in social and genetic mating systems. PMID- 26377433 TI - Another step toward personalized care of patients with heart failure. PMID- 26377434 TI - In memoriam: C. Fergus Lowe 1946-2014. PMID- 26377435 TI - The effects of tact training on the development of analogical reasoning. AB - This study assessed whether tact training would establish analogies as measured by equivalence-equivalence relations. In Experiment 1, six college students were trained to tact "same" or "different" in the presence of AB and BC compounds based on component class membership (e.g., A1B1 as "same", and A1B2 as "different"), and then tested on emergent tacts (BA, CB, AC, CA) and equivalence equivalence relations. Only one of six participants passed all tests without remedial training. In Experiment 2, six college students were trained to tact only compounds belonging to the same class as "same". Three of six participants passed all tests without remedial training. In Experiment 3, six college students were trained to tact stimuli belonging to the same class with a common name prior to exposure to relational tact training. All participants passed tests without remedial training. In Experiment 4, eight college students were trained to tact stimuli belonging to the same class with a common name. Six participants passed without remedial training, while two, who did not tact the relation of the compounds, did not. Results from these studies suggest that simple discrimination of individual components and their relation in the form of tacts is related with equivalence performance. PMID- 26377436 TI - Emergent identity but not symmetry following successive olfactory discrimination training in rats. AB - The search for symmetry in nonhuman subjects has been successful in recent studies in pigeons (e.g., Urcuioli, 2008). The key to these successes has been the use of successive discrimination procedures and combined training on identity, as well as arbitrary, baseline relations. The present study was an effort to extend the findings and theoretical analysis developed by Urcuioli and his colleagues to rats using olfactory rather than visual stimuli. Experiment 1 was a systematic replication of Urcuioli's (2008) demonstration of symmetry in pigeons. Rats were exposed to unreinforced symmetry probes following training with two arbitrary and four identity conditional discriminations. Response rates on symmetry probe trials were low and provided little evidence for emergent symmetry in any of the seven rats tested. In Experiment 2, a separate group of six rats was trained on four identity relations and was then exposed to probe trials with four novel odor stimuli. Response rates were high on identity probe trials, and low on nonmatching probe trials. The similar patterns of responding on baseline and probe trials that were shown by most rats provided a demonstration of generalized identity matching. These findings suggest that the development of stimulus control topographies in rats with olfactory stimuli may differ from those that emerge in pigeons with visual stimuli. Urcuioli's (2008) theory has been highly successful in predicting conditions necessary for stimulus class formation in pigeons, but may not be sufficient to fully understand determinants of emergent behaviors in other nonhuman species. PMID- 26377437 TI - The distribution of response bout lengths and its sensitivity to differential reinforcement. AB - Response bouts are clusters of responses that occur in rapid succession and are punctuated by pauses during which the response does not occur. Under variable interval schedules of reinforcement, the number of responses in each bout (the bout length) varies among bouts. This experiment was aimed at determining whether the relative rate of reinforcement influenced the relative frequency of bouts of different lengths. Lever pressing in rats was reinforced under a tandem variable time (VT) 150-s fixed ratio (FR) X, where X could be 1 or 5 and varied randomly after each reinforcer. Two conditions were included: majority FR1 (mFR1) and majority FR5 (mFR5). In mFR1, 75% of reinforcers had a tandem FR requirement of 1 and 25% had a tandem FR requirement of 5; this distribution was reversed in mFR5. The dynamic bi-exponential refractory model of response bouts was fitted to the interresponse times (IRTs) in each condition. Model parameter estimates and IRTs were then used to simulate probable distributions of bout lengths. These distributions comprised a mixture of short geometrically-distributed bout lengths and long negative-binomially-distributed bout lengths. Long bouts were significantly longer in the mFR5 condition than in the mFR1 condition. In conjunction with previous data, the present study suggests that the prevalence of long bouts increases with the proportion of reinforcers with FR5 requirement. These results suggest that bouts of different lengths are sensitive to the rate at which they are reinforced. PMID- 26377438 TI - The effect of reinforcer magnitude on probability and delay discounting of experienced outcomes in a computer game task in humans. AB - Delay and uncertainty of receipt both reduce the subjective value of reinforcers. Delay has a greater impact on the subjective value of smaller reinforcers than of larger ones while the reverse is true for uncertainty. We investigated the effect of reinforcer magnitude on discounting of delayed and uncertain reinforcers using a novel approach: embedding relevant choices within a computer game. Participants made repeated choices between smaller, certain, immediate outcomes and larger, but delayed or uncertain outcomes while experiencing the result of each choice. Participants' choices were generally well described by the hyperbolic discounting function. Smaller numbers of points were discounted more steeply than larger numbers as a function of delay but not probability. The novel experiential choice task described is a promising approach to investigating both delay and probability discounting in humans. PMID- 26377439 TI - Synthesis and assembly of barium-doped iron oxide nanoparticles and nanomagnets. AB - A facile organic-phase synthesis of monodisperse barium-doped iron oxide (Ba-Fe O) nanoparticles (NPs) is reported. The Ba-Fe-O NPs can be converted into hexagonal barium ferrite NPs at 700 degrees C, showing strong ferromagnetic properties with H(c) reaching 5260 Oe and M(s) at 54 emu g(-1). Moreover, the Ba Fe-O NPs can be assembled into densely packed magnetic arrays, providing a unique model system for studying nanomagnetism and for nanomagnetic applications. PMID- 26377440 TI - What is beautiful brings out what is good in you: The effect of facial attractiveness on individuals' honesty. AB - This study tested whether the presence of an attractive face would influence individuals' honesty. In 2 experiments, 225 participants were asked to predict the outcome of computerised coin-flips and to self-report the accuracy of their predictions. Self-reports were made in the presence of a facial photo of a female who had been rated before the experiment as high attractive, middle attractive or low attractive by other volunteers. Participants were rewarded based on their self-reported (not actual) accuracy. The results showed that subjects tended to give more dishonest self-reports when presented with middle or low attractive facial images than when presented with high attractive images, with self-reported accuracy being significantly higher than the random level. The results of this study show that presented with an attractive face, subjects tend to engage in behaviours that conform to moral codes. PMID- 26377441 TI - Eliminating occupational cancer. PMID- 26377443 TI - Reduction of graphene oxide/alginate composite hydrogels for enhanced adsorption of hydrophobic compounds. AB - Carbon-based materials, consisting of graphene oxide (GO) or reduced GO (rGO), possess unique abilities to interact with various molecules. In particular, rGO materials hold great promise for adsorption and delivery applications of hydrophobic molecules. However, conventional production and/or usage of rGO in aqueous solution often causes severe aggregation due to its low water solubility and thus difficulties in handling and applications. In our study, to prevent the severe aggregation of GO during reduction and to achieve a high adsorption capacity with hydrophobic compounds, GO/alginate composite hydrogels were first prepared and then reduced in an aqueous ascorbic acid solution at 37 degrees C. Adsorption studies with a model hydrophobic substance, rhodamine B, revealed that the reduced composite hydrogels are more highly absorbent than the unreduced hydrogels. In addition, the adsorption properties of the composite hydrogels, which are consequences of hydrophobic and ionic interactions, could be modulated by controlling the degree of reduction for the adsorption of different molecules. The composite hydrogels embedding rGO can be very useful in applications related to drug delivery, waste treatment, and biosensing. PMID- 26377442 TI - Geometric Morphometrics on Gene Expression Patterns Within Phenotypes: A Case Example on Limb Development. AB - How the genotype translates into the phenotype through development is critical to fully understand the evolution of phenotypes. We propose a novel approach to directly assess how changes in gene expression patterns are associated with changes in morphology using the limb as a case example. Our method combines molecular biology techniques, such as whole-mount in situ hybridization, with image and shape analysis, extending the use of Geometric Morphometrics to the analysis of nonanatomical shapes, such as gene expression domains. Elliptical Fourier and Procrustes-based semilandmark analyses were used to analyze the variation and covariation patterns of the limb bud shape with the expression patterns of two relevant genes for limb morphogenesis, Hoxa11 and Hoxa13. We devised a multiple thresholding method to semiautomatically segment gene domains at several expression levels in large samples of limb buds from C57Bl6 mouse embryos between 10 and 12 postfertilization days. Besides providing an accurate phenotyping tool to quantify the spatiotemporal dynamics of gene expression patterns within developing structures, our morphometric analyses revealed high, non-random, and gene-specific variation undergoing canalization during limb development. Our results demonstrate that Hoxa11 and Hoxa13, despite being paralogs with analogous functions in limb patterning, show clearly distinct dynamic patterns, both in shape and size, and are associated differently with the limb bud shape. The correspondence between our results and already well established molecular processes underlying limb development confirms that this morphometric approach is a powerful tool to extract features of development regulating morphogenesis. Such multilevel analyses are promising in systems where not so much molecular information is available and will advance our understanding of the genotype-phenotype map. In systematics, this knowledge will increase our ability to infer how evolution modified a common developmental pattern to generate a wide diversity of morphologies, as in the vertebrate limb. PMID- 26377444 TI - Non-invasive assessment of liver fibrosis and prognosis. AB - Over the past decade, several advances have been made in the non-invasive assessment of liver fibrosis. Both serum markers and imaging-based tissue elastography predict the presence of advanced fibrosis compared with liver biopsy. Serum markers may be indirect or direct markers of liver structure and function. Imaging-based techniques measure liver stiffness as a surrogate for fibrosis and include ultrasound and MRI-based methods. Most non-invasive techniques work well at identifying subjects at the extremes of fibrosis but may not accurately discern intermediate stages. In addition to being a diagnostic tool, elastography may have an evolving role in prognosis. Increasing stiffness is associated with higher rates of liver decompensation, need for transplantation, hepatocellular carcinoma, and death. There are special populations of patients where elastography may serve as a non-invasive method to impart useful clinical information, such as patients after liver transplantation, those with congenital heart disease and those being treated for chronic viral hepatitis. The role of non-invasive markers in accurately predicting the presence of fibrosis in obese patients needs to be further refined. PMID- 26377445 TI - Particularities of Crohn's disease in pediatric patients: current status and perspectives regarding imaging modalities. AB - A consensus on the best imaging modality evaluating inflammatory bowel disease in the pediatric population is lacking and it is often unclear which modality to choose in specific clinical circumstances. Children with inflammatory bowel disease are exposed to ionizing radiation from multiple imaging studies performed at initial diagnosis, throughout treatment and during the follow-up period. This paper discusses the value of different imaging techniques in pediatric patients with inflammatory bowel disease and gives a review of the literature. In addition, particular features of inflammatory bowel disease in children including the predilection of affected segments in the gastrointestinal tract are highlighted. Based on current literature knowledge, we encourage an integrative approach to the interpretation of clinical and imaging data for diagnosis and follow-up in daily clinical settings. PMID- 26377447 TI - Gap-PCR Screening for Common Large Deletional Mutations of beta-Globin Gene Cluster Revealed a Higher Prevalence of the Turkish Inversion/Deletion (deltabeta)0 Mutation in Antalya. AB - OBJECTIVE: Although the calculated carrier frequency for point mutations of the beta-globin gene is around 10% for Antalya Province, nothing is known about the profile of large deletional mutations involving the beta-globin gene. In this study, we aimed to screen common deletional mutations in the beta-globin gene cluster in patients for whom direct DNA sequencing was not able to demonstrate the mutation(s) responsible for the disease phenotype. MATERIALS AND METHODS: Thirty-one index cases selected with a series of selection events among 60 cases without detected beta-globin gene mutation from 580 thalassemia-related cases tested by direct sequencing over the last 4 years in our diagnostic center were screened for the most common 8 different large deletional mutations of the beta globin gene cluster by gap-PCR. RESULTS: We detected 1 homozygous and 9 heterozygous novel unrelated cases for the Turkish inversion/deletion (deltabeta)0 mutation in our series of 31 cases. Our study showed that the Turkish inversion/deletion (deltabeta)0 mutation per se accounts for 16.6% of the unidentified causative alleles and also accounts for 1.5% of all detected mutations over the last 4 years in our laboratory. CONCLUSION: Since molecular diagnosis of deletional mutations in the beta-globin gene cluster warrants different approaches, it deserves special attention in order to provide prenatal diagnosis and prevention opportunities to the families involved. We conclude that the Turkish inversion/deletion (deltabeta)0, as the most prevalent deletional mutation detected so far, has to be routinely tested for in Antalya, and the gap PCR approach has valuable diagnostic potential in the patients at risk. PMID- 26377448 TI - Photo Quiz: A 66-Year-Old Man With Severe Sepsis. PMID- 26377446 TI - Global prevention and control of NCDs: Limitations of the standard approach. AB - The five-target '25 * 25' strategy for tackling the emerging global epidemic of non-communicable diseases (NCDs) focuses on four diseases (CVD, diabetes, cancer, and chronic respiratory disease), four risk factors (tobacco, diet and physical activity, dietary salt, and alcohol), and one cardiovascular preventive drug treatment. The goal is to decrease mortality from NCDs by 25 per cent by the year 2025. The 'standard approach' to the '25 * 25' strategy has the benefit of simplicity, but also has major weaknesses. These include lack of recognition of: (i) the fundamental drivers of the NCD epidemic; (ii) the 'missing NCDs', which are major causes of morbidity; (iii) the 'missing causes' and the 'causes of the causes'; and (iv) the role of health care and the need for integration of interventions. PMID- 26377451 TI - The Contribution of Semantic Features to the White Matter Pathways of Tool Processing. PMID- 26377452 TI - The Neural Representation of Multiple Objects in the Primate Visual System. PMID- 26377453 TI - Representation of Muscle Synergies in the Primate Brain. AB - Evidence suggests that the CNS uses motor primitives to simplify movement control, but whether it actually stores primitives instead of computing solutions on the fly to satisfy task demands is a controversial and still-unanswered possibility. Also in contention is whether these primitives take the form of time invariant muscle coactivations ("spatial" synergies) or time-varying muscle commands ("spatiotemporal" synergies). Here, we examined forelimb muscle patterns and motor cortical spiking data in rhesus macaques (Macaca mulatta) handling objects of variable shape and size. From these data, we extracted both spatiotemporal and spatial synergies using non-negative decomposition. Each spatiotemporal synergy represents a sequence of muscular or neural activations that appeared to recur frequently during the animals' behavior. Key features of the spatiotemporal synergies (including their dimensionality, timing, and amplitude modulation) were independently observed in the muscular and neural data. In addition, both at the muscular and neural levels, these spatiotemporal synergies could be readily reconstructed as sequential activations of spatial synergies (a subset of those extracted independently from the task data), suggestive of a hierarchical relationship between the two levels of synergies. The possibility that motor cortex may execute even complex skill using spatiotemporal synergies has novel implications for the design of neuroprosthetic devices, which could gain computational efficiency by adopting the discrete and low-dimensional control that these primitives imply. SIGNIFICANCE STATEMENT: We studied the motor cortical and forearm muscular activity of rhesus macaques (Macaca mulatta) as they reached, grasped, and carried objects of varied shape and size. We applied non-negative matrix factorization separately to the cortical and muscular data to reduce their dimensionality to a smaller set of time-varying "spatiotemporal" synergies. Each synergy represents a sequence of cortical or muscular activity that recurred frequently during the animals' behavior. Salient features of the synergies (including their dimensionality, timing, and amplitude modulation) were observed at both the cortical and muscular levels. The possibility that the brain may execute even complex behaviors using spatiotemporal synergies has implications for neuroprosthetic algorithm design, which could become more computationally efficient by adopting the discrete and low-dimensional control that they afford. PMID- 26377455 TI - Dynamic Changes from Depolarizing to Hyperpolarizing GABAergic Actions during Giant Depolarizing Potentials in the Neonatal Rat Hippocampus. AB - During development, GABA exerts depolarizing action on immature neurons and, acting in synergy with glutamate, drives giant depolarizing potentials (GDPs) in the hippocampal network. Yet, blockade of the GABA(A) receptors transforms GDPs to epileptiform discharges suggesting dual, both excitatory and inhibitory, actions of GABA in the immature hippocampal network. However, the nature of this dualism in early GABA actions is poorly understood. Here we characterized the dynamics of synaptic currents mediated by GABA(A) and glutamate receptors through an estimation of the changes in their conductance and driving forces in neonatal rat CA3 pyramidal cells during GDPs. We found that depolarizing GABAergic and glutamatergic currents act in synergy at the GDPs' onset. However, during the peak of the population discharge, the inward synaptic current was essentially mediated by glutamate receptors whereas GABA currents transiently switched their direction from depolarizing to hyperpolarizing as a result of neuronal depolarization above the GABA(A) reversal potential. Thus, the action of GABA on CA3 pyramidal cells dynamically changes during GDPs from excitatory at the GDPs' onset to inhibitory at the GDPs' peak. We propose that the dynamic changes in GABA actions occurring during GDPs enable GABAergic interneurons not only to initiate the discharge of pyramidal cells but also to control excitation in the recurrent CA3 network preventing epileptiform synchronization. SIGNIFICANCE STATEMENT: During development GABA exerts a depolarizing action on immature neurons. However, at the network level the effects of GABA are complex involving both excitatory and inhibitory actions. Here we show that GABA actions critically depend on the network state. Although GABA depolarizes neurons at rest and at the onset of population bursts, it transiently becomes hyperpolarizing at the peak of the population bursts. These dynamic changes in GABA actions enable GABAergic interneurons not only to initiate the network discharge but also to control excitation to prevent epileptiform synchronization. PMID- 26377454 TI - Age-Related Differences and Heritability of the Perisylvian Language Networks. AB - Acquisition of language skills depends on the progressive maturation of specialized brain networks that are usually lateralized in adult population. However, how genetic and environmental factors relate to the age-related differences in lateralization of these language pathways is still not known. We recruited 101 healthy right-handed subjects aged 9-40 years to investigate age related differences in the anatomy of perisylvian language pathways and 86 adult twins (52 monozygotic and 34 dizygotic) to understand how heritability factors influence language anatomy. Diffusion tractography was used to dissect and extract indirect volume measures from the three segments of the arcuate fasciculus connecting Wernicke's to Broca's region (i.e., long segment), Broca's to Geschwind's region (i.e., anterior segment), and Wernicke's to Geschwind's region (i.e., posterior segment). We found that the long and anterior arcuate segments are lateralized before adolescence and their lateralization remains stable throughout adolescence and early adulthood. Conversely, the posterior segment shows right lateralization in childhood but becomes progressively bilateral during adolescence, driven by a reduction in volume in the right hemisphere. Analysis of the twin sample showed that genetic and shared environmental factors influence the anatomy of those segments that lateralize earlier, whereas specific environmental effects drive the variability in the volume of the posterior segment that continues to change in adolescence and adulthood. Our results suggest that the age-related differences in the lateralization of the language perisylvian pathways are related to the relative contribution of genetic and environmental effects specific to each segment. SIGNIFICANCE STATEMENT: Our study shows that, by early childhood, frontotemporal (long segment) and frontoparietal (anterior segment) connections of the arcuate fasciculus are left and right lateralized, respectively, and remain lateralized throughout adolescence and early adulthood. In contrast, temporoparietal (posterior segment) connections are right lateralized in childhood, but become progressively bilateral during adolescence. Preliminary twin analysis suggested that lateralization of the arcuate fasciculus is a heterogeneous process that depends on the interplay between genetic and environment factors specific to each segment. Tracts that exhibit higher age effects later in life (i.e., posterior segment) appear to be influenced more by specific environmental factors. PMID- 26377456 TI - Characterization of Cortical Networks and Corticocortical Functional Connectivity Mediating Arbitrary Visuomotor Mapping. AB - Adaptive behaviors are built on the arbitrary linkage of sensory inputs to actions and goals. Although the sensorimotor and associative frontostriatal circuits are known to mediate arbitrary visuomotor mappings, the underlying corticocortico dynamics remain elusive. Here, we take a novel approach exploiting gamma-band neural activity to study the human cortical networks and corticocortical functional connectivity mediating arbitrary visuomotor mapping. Single-trial gamma-power time courses were estimated for all Brodmann areas by combing magnetoencephalographic and MRI data with spectral analysis and beam forming techniques. Linear correlation and Granger causality analyses were performed to investigate functional connectivity between cortical regions. The performance of visuomotor associations was characterized by an increase in gamma power and functional connectivity over the sensorimotor and frontoparietal network, in addition to medial prefrontal areas. The superior parietal area played a driving role in the network, exerting Granger causality on the dorsal premotor area. Premotor areas acted as relay from parietal to medial prefrontal cortices, which played a receiving role in the network. Link community analysis further revealed that visuomotor mappings reflect the coordination of multiple subnetworks with strong overlap over motor and frontoparietal areas. We put forward an associative account of the underlying cognitive processes and corticocortical functional connectivity. Overall, our approach and results provide novel perspectives toward a better understanding of how distributed brain activity coordinates adaptive behaviors. SIGNIFICANCE STATEMENT: In everyday life, most of our behaviors are based on the arbitrary linkage of sensory information to actions and goals, such as stopping at a red traffic light. Despite their automaticity, such behaviors rely on the activity of a large brain network and elusive interareal functional connectivity. We take a novel approach exploiting noninvasive recordings of human brain activity to reveal the cortical networks and corticocortical functional connectivity mediating visuomotor mappings. Parietal areas were found to play a driving role in the network, whereas premotor areas acted as relays from parietal to medial prefrontal cortices, which played a receiving role. Overall, our approach and results provide novel perspectives toward a better understanding of how distributed brain activity coordinates adaptive behaviors. PMID- 26377457 TI - A Simple Network Architecture Accounts for Diverse Reward Time Responses in Primary Visual Cortex. AB - Many actions performed by animals and humans depend on an ability to learn, estimate, and produce temporal intervals of behavioral relevance. Exemplifying such learning of cued expectancies is the observation of reward-timing activity in the primary visual cortex (V1) of rodents, wherein neural responses to visual cues come to predict the time of future reward as behaviorally experienced in the past. These reward-timing responses exhibit significant heterogeneity in at least three qualitatively distinct classes: sustained increase or sustained decrease in firing rate until the time of expected reward, and a class of cells that reach a peak in firing at the expected delay. We elaborate upon our existing model by including inhibitory and excitatory units while imposing simple connectivity rules to demonstrate what role these inhibitory elements and the simple architectures play in sculpting the response dynamics of the network. We find that simply adding inhibition is not sufficient for obtaining the different distinct response classes, and that a broad distribution of inhibitory projections is necessary for obtaining peak-type responses. Furthermore, although changes in connection strength that modulate the effects of inhibition onto excitatory units have a strong impact on the firing rate profile of these peaked responses, the network exhibits robustness in its overall ability to predict the expected time of reward. Finally, we demonstrate how the magnitude of expected reward can be encoded at the expected delay in the network and how peaked responses express this reward expectancy. SIGNIFICANCE STATEMENT: Heterogeneity in single-neuron responses is a common feature of neuronal systems, although sometimes, in theoretical approaches, it is treated as a nuisance and seldom considered as conveying a different aspect of a signal. In this study, we focus on the heterogeneous responses in the primary visual cortex of rodents trained with a predictable delayed reward time. We describe under what conditions this heterogeneity can arise by self-organization, and what information it can convey. This study, while focusing on a specific system, provides insight onto how heterogeneity can arise in general while also shedding light onto mechanisms of reinforcement learning using realistic biological assumptions. PMID- 26377459 TI - Unmasking Proteolytic Activity for Adult Visual Cortex Plasticity by the Removal of Lynx1. AB - Experience-dependent cortical plasticity declines with age. At the molecular level, experience-dependent proteolytic activity of tissue plasminogen activator (tPA) becomes restricted in the adult brain if mice are raised in standard cages. Understanding the mechanism for the loss of permissive proteolytic activity is therefore a key link for improving function in adult brains. Using the mouse primary visual cortex (V1) as a model, we demonstrate that tPA activity in V1 can be unmasked following 4 d of monocular deprivation when the mice older than 2 months are raised in standard cages by the genetic removal of Lynx1, a negative regulator of adult plasticity. This was also associated with the reduction of stubby and thin spine density and enhancement of ocular dominance shift in adult V1 of Lynx1 knock-out (KO) mice. These structural and functional changes were tPA dependent because genetic removal of tPA in Lynx1 KO mice can block the monocular deprivation-dependent reduction of dendritic spine density, whereas both genetic and adult specific inhibition of tPA activity can ablate the ocular dominance shift in Lynx1 KO mice. Our work demonstrates that the adult brain has an intrinsic potential for experience-dependent elevation of proteolytic activity to express juvenile-like structural and functional changes but is effectively limited by Lynx1 if mice are raised in standard cages. Insights into the Lynx1 tPA plasticity mechanism may provide novel therapeutic targets for adult brain disorders. SIGNIFICANCE STATEMENT: Experience-dependent proteolytic activity of tissue plasminogen activator (tPA) becomes restricted in the adult brain in correlation with the decline in cortical plasticity when mice are raised in standard cages. We demonstrated that removal of Lynx1, one of negative regulators of plasticity, unmasks experience-dependent tPA elevation in visual cortex of adult mice reared in standard cages. This proteolytic elevation facilitated dendritic spine reduction and ocular dominance plasticity in adult visual cortex. This is the first demonstration of adult brain to retain the intrinsic capacity to elevate tPA in an experience-dependent manner but is effectively limited by Lynx1. tPA-Lynx1 may potentially be a new candidate mechanism for interventions that were shown to activate plasticity in adult brain. PMID- 26377460 TI - Distinct Functions for Anterograde and Retrograde Sorting of SORLA in Amyloidogenic Processes in the Brain. AB - SORLA is a neuronal sorting receptor implicated both in sporadic and familial forms of AD. SORLA reduces the amyloidogenic burden by two mechanisms, either by rerouting internalized APP molecules from endosomes to the trans-Golgi network (TGN) to prevent proteolytic processing or by directing newly produced Abeta to lysosomes for catabolism. Studies in cell lines suggested that the interaction of SORLA with cytosolic adaptors retromer and GGA is required for receptor sorting to and from the TGN. However, the relevance of anterograde or retrograde trafficking for SORLA activity in vivo remained largely unexplored. Here, we generated mouse models expressing SORLA variants lacking binding sites for GGA or retromer to query this concept in the brain. Disruption of retromer binding resulted in a retrograde-sorting defect with accumulation of SORLA in endosomes and depletion from the TGN, and in an overall enhanced APP processing. In contrast, disruption of the GGA interaction did not impact APP processing but caused increased brain Abeta levels, a mechanism attributed to a defect in anterograde lysosomal targeting of Abeta. Our findings substantiated the significance of adaptor-mediated sorting for SORLA activities in vivo, and they uncovered that anterograde and retrograde sorting paths may serve discrete receptor functions in amyloidogenic processes. SIGNIFICANCE STATEMENT: SORLA is a sorting receptor that directs target proteins to distinct intracellular compartments in neurons. SORLA has been identified as a genetic risk factor for sporadic, but recently also for familial forms of AD. To confirm the relevance of SORLA sorting for AD processes in the brain, we generated mouse lines, which express trafficking mutants instead of the wild-type form of this receptor. Studying neuronal activities in these mutant mice, we dissected distinct trafficking routes for SORLA guided by two cytosolic adaptors termed GGA and retromer. We show that these sorting pathways serve discrete functions in control of amyloidogenic processes and may represent unique therapeutic targets to interfere with specific aspects of neurodegenerative processes in the diseased brain. PMID- 26377458 TI - 3D Shape Perception in Posterior Cortical Atrophy: A Visual Neuroscience Perspective. AB - Posterior cortical atrophy (PCA) is a rare focal neurodegenerative syndrome characterized by progressive visuoperceptual and visuospatial deficits, most often due to atypical Alzheimer's disease (AD). We applied insights from basic visual neuroscience to analyze 3D shape perception in humans affected by PCA. Thirteen PCA patients and 30 matched healthy controls participated, together with two patient control groups with diffuse Lewy body dementia (DLBD) and an amnestic dominant phenotype of AD, respectively. The hierarchical study design consisted of 3D shape processing for 4 cues (shading, motion, texture, and binocular disparity) with corresponding 2D and elementary feature extraction control conditions. PCA and DLBD exhibited severe 3D shape-processing deficits and AD to a lesser degree. In PCA, deficient 3D shape-from-shading was associated with volume loss in the right posterior inferior temporal cortex. This region coincided with a region of functional activation during 3D shape-from-shading in healthy controls. In PCA patients who performed the same fMRI paradigm, response amplitude during 3D shape-from-shading was reduced in this region. Gray matter volume in this region also correlated with 3D shape-from-shading in AD. 3D shape from-disparity in PCA was associated with volume loss slightly more anteriorly in posterior inferior temporal cortex as well as in ventral premotor cortex. The findings in right posterior inferior temporal cortex and right premotor cortex are consistent with neurophysiologically based models of the functional anatomy of 3D shape processing. However, in DLBD, 3D shape deficits rely on mechanisms distinct from inferior temporal structural integrity. SIGNIFICANCE STATEMENT: Posterior cortical atrophy (PCA) is a neurodegenerative syndrome characterized by progressive visuoperceptual dysfunction and most often an atypical presentation of Alzheimer's disease (AD) affecting the ventral and dorsal visual streams rather than the medial temporal system. We applied insights from fundamental visual neuroscience to analyze 3D shape perception in PCA. 3D shape-processing deficits were affected beyond what could be accounted for by lower-order processing deficits. For shading and disparity, this was related to volume loss in regions previously implicated in 3D shape processing in the intact human and nonhuman primate brain. Typical amnestic-dominant AD patients also exhibited 3D shape deficits. Advanced visual neuroscience provides insight into the pathogenesis of PCA that also bears relevance for vision in typical AD. PMID- 26377461 TI - Calcitonin Gene-Related Peptide Reduces Taste-Evoked ATP Secretion from Mouse Taste Buds. AB - Immunoelectron microscopy revealed that peripheral afferent nerve fibers innervating taste buds contain calcitonin gene-related peptide (CGRP), which may be as an efferent transmitter released from peripheral axon terminals. In this report, we determined the targets of CGRP within taste buds and studied what effect CGRP exerts on taste bud function. We isolated mouse taste buds and taste cells, conducted functional imaging using Fura-2, and used cellular biosensors to monitor taste-evoked transmitter release. The findings showed that a subset of Presynaptic (Type III) taste cells (53%) responded to 0.1 MUm CGRP with an increase in intracellular Ca(2+). In contrast, Receptor (Type II) taste cells rarely (4%) responded to 0.1 MUm CGRP. Using pharmacological tools, the actions of CGRP were probed and elucidated by the CGRP receptor antagonist CGRP(8-37). We demonstrated that this effect of CGRP was dependent on phospholipase C activation and was prevented by the inhibitor U73122. Moreover, applying CGRP caused taste buds to secrete serotonin (5-HT), a Presynaptic (Type III) cell transmitter, but not ATP, a Receptor (Type II) cell transmitter. Further, our previous studies showed that 5-HT released from Presynaptic (Type III) cells provides negative paracrine feedback onto Receptor (Type II) cells by activating 5-HT1A receptors, and reducing ATP secretion. Our data showed that CGRP-evoked 5-HT release reduced taste-evoked ATP secretion. The findings are consistent with a role for CGRP as an inhibitory transmitter that shapes peripheral taste signals via serotonergic signaling during processing gustatory information in taste buds. SIGNIFICANCE STATEMENT: The taste sensation is initiated with a highly complex set of interactions between a variety of cells located within the taste buds before signal propagation to the brain. Afferent signals from the oral cavity are carried to the brain in chemosensory fibers that contribute to chemesthesis, the general chemical sensitivity of the mucus membranes in the oronasal cavities and being perceived as pungency, irritation, or heat. This is a study of a fundamental question in neurobiology: how are signals processed in sensory end organs, taste buds? More specifically, taste-modifying interactions, via transmitters, between gustatory and chemosensory afferents inside taste buds will help explain how a coherent output is formed before being transmitted to the brain. PMID- 26377462 TI - Right Frontoinsular Cortex and Subcortical Activity to Infant Cry Is Associated with Maternal Mental State Talk. AB - The study objective was to examine neural correlates of a specific component of human caregiving: maternal mental state talk, reflecting a mother's proclivity to attribute mental states and intentionality to her infant. Using a potent, ecologically relevant stimulus of infant cry during fMRI, we tested hypotheses that postpartum neural response to the cry of "own" versus a standard "other" infant in the right frontoinsular cortex (RFIC) and subcortical limbic network would be associated with independent observations of maternal mental state talk. The sample comprised 76 urban-living, low socioeconomic mothers (82% African American) and their 4-month-old infants. Before the fMRI scan, mothers were filmed in face-to-face interaction with their infant, and maternal behaviors were coded by trained researchers unaware of all other information about the participants. The results showed higher functional activity in the RFIC to own versus other infant cry at the group level. In addition, RFIC and bilateral subcortical neural activity (e.g., thalamus, amygdala, hippocampus, putamen) was associated positively with maternal mental state talk but not with more global aspects of observed caregiving. These findings held when accounting for perceptual and contextual covariates, such as maternal felt distress, urge to help, depression severity, and recognition of own infant cry. Our results highlight the need to focus on specific components of caregiving to advance understanding of the maternal brain. Future work will examine the predictive utility of this neural marker for mother-child function. SIGNIFICANCE STATEMENT: The current study advances extant literature examining the neural underpinning of early parenting behavior. The findings highlight the special functional importance of the right frontoinsular cortex-thalamic-limbic network in a mother's proclivity to engage in mental state talk with her preverbal infant, a circumscribed aspect of maternal caregiving purported to be a prerequisite of sensitive and responsive caregiving. These associations existed specifically for maternal mentalizing behavior and were not evident for more generic aspects of caregiving in this urban sample of 76 postpartum mothers. Finally, the findings were robust even when controlling for potential demographic, perceptual, and contextual confounds, supporting the notion that these regions constitute an innate, specialized maternal mentalizing network. PMID- 26377464 TI - Distinct Modulations in Sensorimotor Postmovement and Foreperiod beta-Band Activities Related to Error Salience Processing and Sensorimotor Adaptation. AB - In a recent study, Tan et al. (2014a,b) showed that the increase in beta-power typically observed after a movement above sensorimotor regions (beta-rebound) is attenuated when movement-execution errors are induced by visual perturbations. Moreover, akin to sensorimotor adaptation, the effect depended on the context in which the errors are experienced. Thus the beta-rebound attenuation might relate to neural processes involved in trial-to-trial adaptive mechanisms. In two EEG experiments with human participants, along with the beta-rebound, we examine beta activity during the preparation of reaches immediately following perturbed movements. In the first experiment, we show that both foreperiod and postmovement beta-activities are parametrically modulated by the sizes of kinematic errors produced by unpredictable mechanical perturbations (force field) independent of their on-line corrections. In the second experiment, we contrast two types of reach errors: movement-execution errors that trigger trial-to-trial adaptive mechanisms and goal errors that do not elicit sensorimotor adaptation. Movement execution errors were induced by mechanical or visual perturbations, whereas goal errors were caused by unexpected displacements of the target at movement initiation. Interestingly, foreperiod and postmovement beta-activities exhibit contrasting patterns, pointing to important functional differences of their underlying neuronal activity. While both types of reach errors attenuate the postmovement beta-rebound, only the kinematic errors that trigger trial-to-trial motor-command updates influenced beta-activity during the foreperiod. These findings suggest that the error-related modulation of the beta-rebound may reflect salience processing, independent of sensorimotor adaptation. In contrast, modulations in the foreperiod beta-power might relate to the motor-command adjustments activated after movement-execution errors are experienced. SIGNIFICANCE STATEMENT: The functional significance of sensorimotor beta-band (15 25 Hz) oscillations remains uncertain. Recently beta-power was found to be reduced following erroneous movements. We extend and refine this novel finding in two crucial ways. First, by contrasting the EEG correlates of movement errors driving or not driving adaptation we dissociate error-salience processing from error-based adaptation. Second, in addition to beta-activity in error trials, we examine beta-power during the preparation of the subsequent movements. We find clearly distinct patterns of error-related modulations for beta-activities preceding and succeeding movements, highlighting critical functional differences. Postmovement beta-power may reflect error-salience processing independent of sensorimotor adaptation. In contrast, modulations in the foreperiod beta-band power may directly relate to the motor-command adjustments activated after movement-execution errors are experienced. PMID- 26377463 TI - A Single Bolus of Docosahexaenoic Acid Promotes Neuroplastic Changes in the Innervation of Spinal Cord Interneurons and Motor Neurons and Improves Functional Recovery after Spinal Cord Injury. AB - Docosahexaenoic acid (DHA) is an omega-3 polyunsaturated fatty acid that is essential in brain development and has structural and signaling roles. Acute DHA administration is neuroprotective and promotes functional recovery in animal models of adult spinal cord injury (SCI). However, the mechanisms underlying this recovery have not been fully characterized. Here we investigated the effects of an acute intravenous bolus of DHA delivered after SCI and characterized DHA induced neuroplasticity within the adult injured spinal cord. We found robust sprouting of uninjured corticospinal and serotonergic fibers in a rat cervical hemisection SCI model. A mouse pyramidotomy model was used to confirm that this robust sprouting was not species or injury model specific. Furthermore, we demonstrated that corticospinal fibers sprouting to the denervated side of the cord following pyramidotomy contact V2a interneurons. We also demonstrated increased serotonin fibers and synaptophysin in direct contact with motor neurons. DHA also increased synaptophysin in rat cortical cell cultures. A reduction in phosphatase and tensin homolog (PTEN) has been shown to be involved in axonal regeneration and synaptic plasticity. We showed that DHA significantly upregulates miR-21 and downregulates PTEN in corticospinal neurons. Downregulation of PTEN and upregulation of phosphorylated AKT by DHA were also seen in primary cortical neuron cultures and were accompanied by increased neurite outgrowth. In summary, acute DHA induces anatomical and synaptic plasticity in adult injured spinal cord. This study shows that DHA has therapeutic potential in cervical SCI and provides evidence that DHA could exert its beneficial effects in SCI via enhancement of neuroplasticity. SIGNIFICANCE STATEMENT: In this study, we show that an acute intravenous injection of docosahexaenoic acid (DHA) 30 min after spinal cord injury induces neuroplasticity. We found robust sprouting of uninjured corticospinal and serotonergic fibers in a rat hemisection spinal cord injury model. A mouse pyramidotomy model was used to confirm that the robust sprouting involved V2a interneurons. We show that DHA significantly upregulates miR-21 and phosphorylated AKT, and downregulates phosphatase and tensin homolog (PTEN), which is involved in suppressing anatomical plasticity, in corticospinal neurons and in primary cortical neuron cultures. We conclude that acute DHA can induce anatomical and synaptic plasticity. This provides direct evidence that DHA could exert its beneficial effects in spinal cord injury via neuroplasticity enhancement. PMID- 26377465 TI - Amyloid beta Oligomers Disrupt Blood-CSF Barrier Integrity by Activating Matrix Metalloproteinases. AB - The blood-CSF barrier (BCSFB) consists of a monolayer of choroid plexus epithelial (CPE) cells that maintain CNS homeostasis by producing CSF and restricting the passage of undesirable molecules and pathogens into the brain. Alzheimer's disease is the most common progressive neurodegenerative disorder and is characterized by the presence of amyloid beta (Abeta) plaques and neurofibrillary tangles in the brain. Recent research shows that Alzheimer's disease is associated with morphological changes in CPE cells and compromised production of CSF. Here, we studied the direct effects of Abeta on the functionality of the BCSFB. Intracerebroventricular injection of Abeta1-42 oligomers into the cerebral ventricles of mice, a validated Alzheimer's disease model, caused induction of a cascade of detrimental events, including increased inflammatory gene expression in CPE cells and increased levels of proinflammatory cytokines and chemokines in the CSF. It also rapidly affected CPE cell morphology and tight junction protein levels. These changes were associated with loss of BCSFB integrity, as shown by an increase in BCSFB leakage. Abeta1-42 oligomers also increased matrix metalloproteinase (MMP) gene expression in the CPE and its activity in CSF. Interestingly, BCSFB disruption induced by Abeta1-42 oligomers did not occur in the presence of a broad-spectrum MMP inhibitor or in MMP3 deficient mice. These data provide evidence that MMPs are essential for the BCSFB leakage induced by Abeta1-42 oligomers. Our results reveal that Alzheimer's disease-associated soluble Abeta1-42 oligomers induce BCSFB dysfunction and suggest MMPs as a possible therapeutic target. SIGNIFICANCE STATEMENT: No treatments are yet available to cure Alzheimer's disease; however, soluble Abeta oligomers are believed to play a crucial role in the neuroinflammation that is observed in this disease. Here, we studied the effect of Abeta oligomers on the often neglected barrier between blood and brain, called the blood-CSF barrier (BCSFB). This BCSFB is formed by the choroid plexus epithelial cells and is important in maintaining brain homeostasis. We observed Abeta oligomer-induced changes in morphology and loss of BCSFB integrity that might play a role in Alzheimer's disease progression. Strikingly, both inhibition of matrix metalloproteinase (MMP) activity and MMP3 deficiency could protect against the detrimental effects of Abeta oligomer. Clearly, our results suggest that MMP inhibition might have therapeutic potential. PMID- 26377467 TI - Identified Serotonin-Releasing Neurons Induce Behavioral Quiescence and Suppress Mating in Drosophila. AB - Animals show different levels of activity that are reflected in sensory responsiveness and endogenously generated behaviors. Biogenic amines have been determined to be causal factors for these states of arousal. It is well established that, in Drosophila, dopamine and octopamine promote increased arousal. However, little is known about factors that regulate arousal negatively and induce states of quiescence. Moreover, it remains unclear whether global, diffuse modulatory systems comprehensively affecting brain activity determine general states of arousal. Alternatively, individual aminergic neurons might selectively modulate the animals' activity in a distinct behavioral context. Here, we show that artificially activating large populations of serotonin releasing neurons induces behavioral quiescence and inhibits feeding and mating. We systematically narrowed down a role of serotonin in inhibiting endogenously generated locomotor activity to neurons located in the posterior medial protocerebrum. We identified neurons of this cell cluster that suppress mating, but not feeding behavior. These results suggest that serotonin does not uniformly act as global, negative modulator of general arousal. Rather, distinct serotoninergic neurons can act as inhibitory modulators of specific behaviors. SIGNIFICANCE STATEMENT: An animal's responsiveness to external stimuli and its various types of endogenously generated, motivated behavior are highly dynamic and change between states of high activity and states of low activity. It remains unclear whether these states are mediated by unitary modulatory systems globally affecting brain activity, or whether distinct neurons modulate specific neuronal circuits underlying particular types of behavior. Using the model organism Drosophila melanogaster, we find that activating large proportions of serotonin releasing neurons induces behavioral quiescence. Moreover, distinct serotonin releasing neurons that we genetically isolated and identified negatively affect aspects of mating behavior, but not food uptake. This demonstrates that individual serotoninergic neurons can modulate distinct types of behavior selectively. PMID- 26377466 TI - Impaired Cholinergic Excitation of Prefrontal Attention Circuitry in the TgCRND8 Model of Alzheimer's Disease. AB - Attention deficits in Alzheimer's disease can exacerbate its other cognitive symptoms, yet relevant disruptions of key prefrontal circuitry are not well understood. Here, in the TgCRND8 mouse model of this neurological disorder, we demonstrate and characterize a disruption of cholinergic excitation in the major corticothalamic layer of the prefrontal cortex, in which modulation by acetylcholine is essential for optimal attentional function. Using electrophysiology with concurrent multiphoton imaging, we show that layer 6 pyramidal cells are unable to sustain cholinergic excitation to the same extent as their nontransgenic littermate controls, as a result of the excessive activation of calcium-activated hyperpolarizing conductances. We report that cholinergic excitation can be improved in TgCRND8 cortex by pharmacological blockade of SK channels, suggesting a novel target for the treatment of cognitive dysfunction in Alzheimer's disease. SIGNIFICANCE STATEMENT: Alzheimer's disease is accompanied by attention deficits that exacerbate its other cognitive symptoms. In brain slices of a mouse model of this neurological disorder, we demonstrate, characterize, and rescue impaired cholinergic excitation of neurons essential for optimal attentional performance. In particular, we show that the excessive activation of a calcium-activated potassium conductance disrupts the acetylcholine excitation of prefrontal layer 6 pyramidal neurons and that its blockade normalizes responses. These findings point to a novel potential target for the treatment of cognitive dysfunction in Alzheimer's disease. PMID- 26377468 TI - Ventromedial Frontal Cortex Is Critical for Guiding Attention to Reward Predictive Visual Features in Humans. AB - Adaptively interacting with our environment requires extracting information that will allow us to successfully predict reward. This can be a challenge, particularly when there are many candidate cues, and when rewards are probabilistic. Recent work has demonstrated that visual attention is allocated to stimulus features that have been associated with reward on previous trials. The ventromedial frontal lobe (VMF) has been implicated in learning in dynamic environments of this kind, but the mechanism by which this region influences this process is not clear. Here, we hypothesized that the VMF plays a critical role in guiding attention to reward-predictive stimulus features based on feedback. We tested the effects of VMF damage in human subjects on a visual search task in which subjects were primed to attend to task-irrelevant colors associated with different levels of reward, incidental to the search task. Consistent with previous work, we found that distractors had a greater influence on reaction time when they appeared in colors associated with high reward in the previous trial compared with colors associated with low reward in healthy control subjects and patients with prefrontal damage sparing the VMF. However, this reward modulation of attentional priming was absent in patients with VMF damage. Thus, an intact VMF is necessary for directing attention based on experience with cue-reward associations. We suggest that this region plays a role in selecting reward predictive cues to facilitate future learning. SIGNIFICANCE STATEMENT: There has been a swell of interest recently in the ventromedial frontal cortex (VMF), a brain region critical to associative learning. However, the underlying mechanism by which this region guides learning is not well understood. Here, we tested the effects of damage to this region in humans on a task in which rewards were linked incidentally to visual features, resulting in trial-by-trial attentional priming. Controls and subjects with prefrontal damage sparing the VMF showed normal reward priming, but VMF-damaged patients did not. This work sheds light on a potential mechanism through which this region influences behavior. We suggest that the VMF is necessary for directing attention to reward-predictive visual features based on feedback, facilitating future learning and decision-making. PMID- 26377469 TI - Modulating Hippocampal Plasticity with In Vivo Brain Stimulation. AB - Investigations into the use of transcranial direct current stimulation (tDCS) in relieving symptoms of neurological disorders and enhancing cognitive or motor performance have exhibited promising results. However, the mechanisms by which tDCS effects brain function remain under scrutiny. We have demonstrated that in vivo tDCS in rats produced a lasting effect on hippocampal synaptic plasticity, as measured using extracellular recordings. Ex vivo preparations of hippocampal slices from rats that have been subjected to tDCS of 0.10 or 0.25 mA for 30 min followed by 30 min of recovery time displayed a robust twofold enhancement in long-term potentiation (LTP) induction accompanied by a 30% increase in paired pulse facilitation (PPF). The magnitude of the LTP effect was greater with 0.25 mA compared with 0.10 mA stimulations, suggesting a dose-dependent relationship between tDCS intensity and its effect on synaptic plasticity. To test the persistence of these observed effects, animals were stimulated in vivo for 30 min at 0.25 mA and then allowed to return to their home cage for 24 h. Observation of the enhanced LTP induction, but not the enhanced PPF, continued 24 h after completion of 0.25 mA of tDCS. Addition of the NMDA blocker AP-5 abolished LTP in both control and stimulated rats but maintained the PPF enhancement in stimulated rats. The observation of enhanced LTP and PPF after tDCS demonstrates that non invasive electrical stimulation is capable of modifying synaptic plasticity. SIGNIFICANCE STATEMENT: Researchers have used brain stimulation such as transcranial direct current stimulation on human subjects to alleviate symptoms of neurological disorders and enhance their performance. Here, using rats, we have investigated the potential mechanisms of how in vivo brain stimulation can produce such effect. We recorded directly on viable brain slices from rats after brain stimulation to detect lasting changes in pattern of neuronal activity. Our results showed that 30 min of brain stimulation in rats induced a robust enhancement in synaptic plasticity, a neuronal process critical for learning and memory. Understanding such molecular effects will lead to a better understanding of the mechanisms by which brain stimulation produces its effects on cognition and performance. PMID- 26377470 TI - Mitochondrial Quality Control via the PGC1alpha-TFEB Signaling Pathway Is Compromised by Parkin Q311X Mutation But Independently Restored by Rapamycin. AB - Following its activation by PINK1, parkin is recruited to depolarized mitochondria where it ubiquitinates outer mitochondrial membrane proteins, initiating lysosomal-mediated degradation of these organelles. Mutations in the gene encoding parkin, PARK2, result in both familial and sporadic forms of Parkinson's disease (PD) in conjunction with reductions in removal of damaged mitochondria. In contrast to what has been reported for other PARK2 mutations, expression of the Q311X mutation in vivo in mice appears to involve a downstream step in the autophagic pathway at the level of lysosomal function. This coincides with increased PARIS expression and reduced expression of a reciprocal signaling pathway involving the master mitochondrial regulator peroxisome proliferator activated receptor-gamma coactivator (PGC1alpha) and the lysosomal regulator transcription factor EB (TFEB). Treatment with rapamycin was found to independently restore PGC1alpha-TFEB signaling in a manner not requiring parkin activity and to abrogate impairment of mitochondrial quality control and neurodegenerative features associated with this in vivo model. Losses in PGC1alpha-TFEB signaling in cultured rat DAergic cells expressing the Q311X mutation associated with reduced mitochondrial function and cell viability were found to be PARIS-dependent and to be independently restored by rapamycin in a manner requiring TFEB. Studies in human iPSC-derived neurons demonstrate that TFEB induction can restore mitochondrial function and cell viability in a mitochondrially compromised human cell model. Based on these data, we propose that the parkin Q311X mutation impacts on mitochondrial quality control via PARIS mediated regulation of PGC1alpha-TFEB signaling and that this can be independently restored via upregulation of TFEB function. SIGNIFICANCE STATEMENT: Mutations in PARK2 are generally associated with loss in ability to interact with PINK1, impacting on autophagic initiation. Our data suggest that, in the case of at least one parkin mutation, Q311X, detrimental effects are due to inhibition at the level of downstream lysosomal function. Mechanistically, this involves elevations in PARIS protein levels and subsequent effects on PGC1alpha-TFEB signaling that normally regulates mitochondrial quality control. Treatment with rapamycin independently restores PGC1alpha-TFEB signaling in a manner not requiring parkin activity and abrogates subsequent mitochondrial impairment and neuronal cell loss. Taken in total, our data suggest that the parkin Q311X mutation impacts on mitochondrial quality control via PARIS-mediated regulation of PGC1alpha-TFEB signaling and that this can be independently restored via rapamycin. PMID- 26377471 TI - Brain Region-Specific Trafficking of the Dopamine Transporter. AB - The dopamine (DA) transporter (DAT) controls dopaminergic neurotransmission by removing extracellular DA. Although DA reuptake is proposed to be regulated by DAT traffic to and from the cell surface, the membrane trafficking system involved in the endocytic cycling of DAT in the intact mammalian brain has not been characterized. Hence, we performed immunolabeling and quantitative analysis of the subcellular and regional distribution of DAT using the transgenic knock-in mouse expressing hemagglutinin (HA) epitope-tagged DAT (HA-DAT) and by using a combination of electron microscopy and a novel method for immunofluorescence labeling of HA-DAT in acute sagittal brain slices. Both approaches demonstrated that, in midbrain somatodendritic regions, HA-DAT was present in the plasma membrane, endoplasmic reticulum, and Golgi complex, with a small fraction in early and recycling endosomes and an even smaller fraction in late endosomes and lysosomes. In the striatum and in axonal tracts between the midbrain and striatum, HA-DAT was detected predominantly in the plasma membrane, and quantitative analysis revealed increased DAT density in striatal compared with midbrain plasma membranes. Endosomes were strikingly rare and lysosomes were absent in striatal axons, in which there was little intracellular HA-DAT. Acute administration of amphetamine in vivo (60 min) or to slices ex vivo (10-60 min) did not result in detectable changes in DAT distribution. Altogether, these data provide evidence for regional differences in DAT plasma membrane targeting and retention and suggest a surprisingly low level of endocytic trafficking of DAT in the striatum along with limited DAT endocytic activity in somatodendritic areas. SIGNIFICANCE STATEMENT: The dopamine transporter (DAT) is the key regulator of the dopamine neurotransmission in the CNS. In the present study, we developed a new approach for studying DAT localization and dynamics in intact neurons in acute sagittal brain slices from the knock-in mouse expressing epitope-tagged DAT. For the first time, the fluorescence imaging analysis of DAT was combined with the immunogold labeling of DAT and quantitative electron microscopy. In contrast to numerous studies of DAT trafficking in heterologous expression systems and dissociated cultured neurons, studies in intact neurons revealed a surprisingly low amount of endocytic trafficking of DAT at steady state and after acute amphetamine treatment and suggested that non-vesicular transport could be the main mechanism establishing DAT distribution within the dopaminergic neuron. PMID- 26377472 TI - "Visual" Cortex of Congenitally Blind Adults Responds to Syntactic Movement. AB - Human cortex is comprised of specialized networks that support functions, such as visual motion perception and language processing. How do genes and experience contribute to this specialization? Studies of plasticity offer unique insights into this question. In congenitally blind individuals, "visual" cortex responds to auditory and tactile stimuli. Remarkably, recent evidence suggests that occipital areas participate in language processing. We asked whether in blindness, occipital cortices: (1) develop domain-specific responses to language and (2) respond to a highly specialized aspect of language-syntactic movement. Nineteen congenitally blind and 18 sighted participants took part in two fMRI experiments. We report that in congenitally blind individuals, but not in sighted controls, "visual" cortex is more active during sentence comprehension than during a sequence memory task with nonwords, or a symbolic math task. This suggests that areas of occipital cortex become selective for language, relative to other similar higher-cognitive tasks. Crucially, we find that these occipital areas respond more to sentences with syntactic movement but do not respond to the difficulty of math equations. We conclude that regions within the visual cortex of blind adults are involved in syntactic processing. Our findings suggest that the cognitive function of human cortical areas is largely determined by input during development. SIGNIFICANCE STATEMENT: Human cortex is made up of specialized regions that perform different functions, such as visual motion perception and language processing. How do genes and experience contribute to this specialization? Studies of plasticity show that cortical areas can change function from one sensory modality to another. Here we demonstrate that input during development can alter cortical function even more dramatically. In blindness a subset of "visual" areas becomes specialized for language processing. Crucially, we find that the same "visual" areas respond to a highly specialized and uniquely human aspect of language-syntactic movement. These data suggest that human cortex has broad functional capacity during development, and input plays a major role in determining functional specialization. PMID- 26377474 TI - Arginine Methyltransferase 1 in the Nucleus Accumbens Regulates Behavioral Effects of Cocaine. AB - Recent evidence suggests that histone modifications play a role in the behavioral effects of cocaine in rodent models. Histone arginine is known to be methylated by protein arginine N-methyltransferases (PRMTs). Evidence shows that PRMT1 contributes to >90% of cellular PRMT activity, which regulates histone H4 arginine 3 asymmetric dimethylation (H4R3me2a). Though histone arginine methylation represents a chemical modification that is relatively stable compared with other histone alterations, it is less well studied in the setting of addiction. Here, we demonstrate that repeated noncontingent cocaine injections increase PRMT1 activity in the nucleus accumbens (NAc) of C57BL/6 mice. We, subsequently, identify a selective inhibitor of PRMT1, SKLB-639, and show that systemic injections of the drug decrease cocaine-induced conditioned place preference to levels observed with genetic knockdown of PRMT1. NAc-specific downregulation of PRMT1 leads to hypomethylation of H4R3me2a, and hypoacetylation of histone H3 lysine 9 and 14. We also found that H4R3me2a is upregulated in NAc after repeated cocaine administration, and that H4R3me2a upregulation in turn controls the expression of Cdk5 and CaMKII. Additionally, the suppression of PRMT1 in NAc with lentiviral-short hairpin PMRT1 decreases levels of CaMKII and Cdk5 in the cocaine-treated group, demonstrating that PRMT1 affects the ability of cocaine to induce CaMKII and Cdk5 in NAc. Notably, increased H4R3me2a by repeated cocaine injections is relatively long-lived, as increased expression was observed for up to 7 d after the last cocaine injection. These results show the role of PRMT1 in the behavioral effects of cocaine. SIGNIFICANCE STATEMENT: This work demonstrated that repeated cocaine injections led to an increase of protein arginine N-methyltransferase (PRMT1) in nucleus accumbens (NAc). We then identified a selective inhibitor of PRMT1 (SKLB-639), which inhibited cocaine induced conditioned place preference (CPP). Additionally, genetic downregulation of PRMT1 in NAc also attenuated cocaine-caused CPP and locomotion activity, which was associated with decreased expression of histone H4 arginine 3 asymmetric demethylation (H4R3me2a) and hypoacetylation of histone H3 lysine 9 and 14 (acH3K9/K14). This study also showed that H4R3me2a controlled transcriptions of Cdk5 and CaMKII, and that PRMT1 negatively affected the ability of cocaine to induce CaMKII and Cdk5 in NAc. Notably, increased H4R3me2a by repeated cocaine injection was relatively long-lived as increased expression was observed up to 7 d after withdrawal from cocaine. Together, this study suggests that PRMT1 inhibition may serve as a potential therapeutic strategy for cocaine addiction. PMID- 26377473 TI - Prox1 Regulates the Subtype-Specific Development of Caudal Ganglionic Eminence Derived GABAergic Cortical Interneurons. AB - Neurogliaform (RELN+) and bipolar (VIP+) GABAergic interneurons of the mammalian cerebral cortex provide critical inhibition locally within the superficial layers. While these subtypes are known to originate from the embryonic caudal ganglionic eminence (CGE), the specific genetic programs that direct their positioning, maturation, and integration into the cortical network have not been elucidated. Here, we report that in mice expression of the transcription factor Prox1 is selectively maintained in postmitotic CGE-derived cortical interneuron precursors and that loss of Prox1 impairs the integration of these cells into superficial layers. Moreover, Prox1 differentially regulates the postnatal maturation of each specific subtype originating from the CGE (RELN, Calb2/VIP, and VIP). Interestingly, Prox1 promotes the maturation of CGE-derived interneuron subtypes through intrinsic differentiation programs that operate in tandem with extrinsically driven neuronal activity-dependent pathways. Thus Prox1 represents the first identified transcription factor specifically required for the embryonic and postnatal acquisition of CGE-derived cortical interneuron properties. SIGNIFICANCE STATEMENT: Despite the recognition that 30% of GABAergic cortical interneurons originate from the caudal ganglionic eminence (CGE), to date, a specific transcriptional program that selectively regulates the development of these populations has not yet been identified. Moreover, while CGE-derived interneurons display unique patterns of tangential and radial migration and preferentially populate the superficial layers of the cortex, identification of a molecular program that controls these events is lacking.Here, we demonstrate that the homeodomain transcription factor Prox1 is expressed in postmitotic CGE derived cortical interneuron precursors and is maintained into adulthood. We found that Prox1 function is differentially required during both embryonic and postnatal stages of development to direct the migration, differentiation, circuit integration, and maintenance programs within distinct subtypes of CGE-derived interneurons. PMID- 26377475 TI - GnRH Neuron-Specific Ablation of Galphaq/11 Results in Only Partial Inactivation of the Neuroendocrine-Reproductive Axis in Both Male and Female Mice: In Vivo Evidence for Kiss1r-Coupled Galphaq/11-Independent GnRH Secretion. AB - The gonadotropin-releasing hormone (GnRH) is the master regulator of fertility and kisspeptin (KP) is a potent trigger of GnRH secretion from GnRH neurons. KP signals via KISS1R, a Galphaq/11-coupled receptor, and mice bearing a global deletion of Kiss1r (Kiss1r(-/-)) or a GnRH neuron-specific deletion of Kiss1r (Kiss1r(d/d)) display hypogonadotropic hypogonadism and infertility. KISS1R also signals via beta-arrestin, and in mice lacking beta-arrestin-1 or -2, KP triggered GnRH secretion is significantly diminished. Based on these findings, we hypothesized that ablation of Galphaq/11 in GnRH neurons would diminish but not completely block KP-triggered GnRH secretion and that Galphaq/11-independent GnRH secretion would be sufficient to maintain fertility. To test this, Gnaq (encodes Galphaq) was selectively inactivated in the GnRH neurons of global Gna11 (encodes Galpha11)-null mice by crossing Gnrh-Cre and Gnaq(fl/fl);Gna11(-/-) mice. Experimental Gnaq(fl/fl);Gna11(-/-);Gnrh-Cre (Gnaq(d/d)) and control Gnaq(fl/fl);Gna11(-/-) (Gnaq(fl/fl)) littermate mice were generated and subjected to reproductive profiling. This process revealed that testicular development and spermatogenesis, preputial separation, and anogenital distance in males and day of vaginal opening and of first estrus in females were significantly less affected in Gnaq(d/d) mice than in previously characterized Kiss1r(-/-) or Kiss1r(d/d) mice. Additionally, Gnaq(d/d) males were subfertile, and although Gnaq(d/d) females did not ovulate spontaneously, they responded efficiently to a single dose of gonadotropins. Finally, KP stimulation triggered a significant increase in gonadotropins and testosterone levels in Gnaq(d/d) mice. We therefore conclude that the milder reproductive phenotypes and maintained responsiveness to KP and gonadotropins reflect Galphaq/11-independent GnRH secretion and activation of the neuroendocrine-reproductive axis in Gnaq(d/d) mice. SIGNIFICANCE STATEMENT: The gonadotropin-releasing hormone (GnRH) is the master regulator of fertility. Over the last decade, several studies have established that the KISS1 receptor, KISS1R, is a potent trigger of GnRH secretion and inactivation of KISS1R on the GnRH neuron results in infertility. While KISS1R is best understood as a Galphaq/11-coupled receptor, we previously demonstrated that it could couple to and signal via non-Galphaq/11-coupled pathways. The present study confirms these findings and, more importantly, while it establishes Galphaq/11-coupled signaling as a major conduit of GnRH secretion, it also uncovers a significant role for non-Galphaq/11-coupled signaling in potentiating reproductive development and function. This study further suggests that by augmenting signaling via these pathways, GnRH secretion can be enhanced to treat some forms of infertility. PMID- 26377478 TI - Spontaneous Activity Patterns in Primary Visual Cortex Predispose to Visual Hallucinations. AB - According to theoretical frameworks casting perception as inference, vision results from the integration of bottom-up visual input with top-down expectations. Under conditions of strongly degraded sensory input, this may occasionally result in false perceptions in the absence of a sensory signal, also termed "hallucinations." Here, we investigated whether spontaneous prestimulus activity patterns in sensory circuits, which may embody a participant's prior expectations, predispose the observer toward false perceptions. Specifically, we used fMRI to investigate whether the representational content of prestimulus activity in early visual cortex is linked to subsequent perception during a challenging detection task. Human participants were asked to detect oriented gratings of a particular orientation that were embedded in noise. We found two characteristics of prestimulus activity that predisposed participants to hallucinations: overall lower prestimulus activity and a bias in the prestimulus activity patterns toward the to-be-detected (expected) grating. These results suggest that perceptual hallucinations may be due to an imprecise and biased state of sensory circuits preceding sensory evidence collection. SIGNIFICANCE STATEMENT: When sensory stimulation is strongly degraded, we occasionally misperceive a stimulus when only noise is present: a perceptual hallucination. Using fMRI in healthy participants, we investigated whether the state of early visual cortex preceding stimulus onset predisposes an observer to hallucinations. We found two characteristics of prestimulus activity that predisposed participants to hallucinations: overall lower prestimulus activity and a bias in the prestimulus activity patterns toward the expected grating. These results suggest that perceptual hallucinations are due to an imprecise and biased state of sensory circuits preceding sensation. PMID- 26377476 TI - Kappa Opioid Receptor-Induced Aversion Requires p38 MAPK Activation in VTA Dopamine Neurons. AB - The endogenous dynorphin-kappa opioid receptor (KOR) system encodes the dysphoric component of the stress response and controls the risk of depression-like and addiction behaviors; however, the molecular and neural circuit mechanisms are not understood. In this study, we report that KOR activation of p38alpha MAPK in ventral tegmental (VTA) dopaminergic neurons was required for conditioned place aversion (CPA) in mice. Conditional genetic deletion of floxed KOR or floxed p38alpha MAPK by Cre recombinase expression in dopaminergic neurons blocked place aversion to the KOR agonist U50,488. Selective viral rescue by wild-type KOR expression in dopaminergic neurons of KOR(-/-) mice restored U50,488-CPA, whereas expression of a mutated form of KOR that could not initiate p38alpha MAPK activation did not. Surprisingly, while p38alpha MAPK inactivation blocked U50,488-CPA, p38alpha MAPK was not required for KOR inhibition of evoked dopamine release measured by fast scan cyclic voltammetry in the nucleus accumbens. In contrast, KOR activation acutely inhibited VTA dopaminergic neuron firing, and repeated exposure attenuated the opioid response. This adaptation to repeated exposure was blocked by conditional deletion of p38alpha MAPK, which also blocked KOR-induced tyrosine phosphorylation of the inwardly rectifying potassium channel (GIRK) subunit Kir3.1 in VTA dopaminergic neurons. Consistent with the reduced response, GIRK phosphorylation at this amino terminal tyrosine residue (Y12) enhances channel deactivation. Thus, contrary to prevailing expectations, these results suggest that kappa opioid-induced aversion requires regulation of VTA dopaminergic neuron somatic excitability through a p38alpha MAPK effect on GIRK deactivation kinetics rather than by presynaptically inhibiting dopamine release. SIGNIFICANCE STATEMENT: Kappa opioid receptor (KOR) agonists have the potential to be effective, nonaddictive analgesics, but their therapeutic utility is greatly limited by adverse effects on mood. Understanding how KOR activation produces dysphoria is key to the development of better analgesics and to defining how the endogenous dynorphin opioids produce their depression-like effects. Results in this study show that the aversive effects of kappa receptor activation required arrestin-dependent p38alpha MAPK activation in dopamine neurons but did not require inhibition of dopamine release in the nucleus accumbens. Thus, contrary to the prevailing view, inhibition of mesolimbic dopamine release does not mediate the aversive effects of KOR activation and functionally selective kappa opioids that do not activate arrestin signaling may be effective analgesics lacking dysphoric effects. PMID- 26377477 TI - Intrinsic Functional Connectivity Patterns Predict Consciousness Level and Recovery Outcome in Acquired Brain Injury. AB - For accurate diagnosis and prognostic prediction of acquired brain injury (ABI), it is crucial to understand the neurobiological mechanisms underlying loss of consciousness. However, there is no consensus on which regions and networks act as biomarkers for consciousness level and recovery outcome in ABI. Using resting state fMRI, we assessed intrinsic functional connectivity strength (FCS) of whole brain networks in a large sample of 99 ABI patients with varying degrees of consciousness loss (including fully preserved consciousness state, minimally conscious state, unresponsive wakefulness syndrome/vegetative state, and coma) and 34 healthy control subjects. Consciousness level was evaluated using the Glasgow Coma Scale and Coma Recovery Scale-Revised on the day of fMRI scanning; recovery outcome was assessed using the Glasgow Outcome Scale 3 months after the fMRI scanning. One-way ANOVA of FCS, Spearman correlation analyses between FCS and the consciousness level and recovery outcome, and FCS-based multivariate pattern analysis were performed. We found decreased FCS with loss of consciousness primarily distributed in the posterior cingulate cortex/precuneus (PCC/PCU), medial prefrontal cortex, and lateral parietal cortex. The FCS values of these regions were significantly correlated with consciousness level and recovery outcome. Multivariate support vector machine discrimination analysis revealed that the FCS patterns predicted whether patients with unresponsive wakefulness syndrome/vegetative state and coma would regain consciousness with an accuracy of 81.25%, and the most discriminative region was the PCC/PCU. These findings suggest that intrinsic functional connectivity patterns of the human posteromedial cortex could serve as a potential indicator for consciousness level and recovery outcome in individuals with ABI. SIGNIFICANCE STATEMENT: Varying degrees of consciousness loss and recovery are commonly observed in acquired brain injury patients, yet the underlying neurobiological mechanisms remain elusive. Using a large sample of patients with varying degrees of consciousness loss, we demonstrate that intrinsic functional connectivity strength in many brain regions, especially in the posterior cingulate cortex and precuneus, significantly correlated with consciousness level and recovery outcome. We further demonstrate that the functional connectivity pattern of these regions can predict patients with unresponsive wakefulness syndrome/vegetative state and coma would regain consciousness with an accuracy of 81.25%. Our study thus provides potentially important biomarkers of acquired brain injury in clinical diagnosis, prediction of recovery outcome, and decision making for treatment strategies for patients with severe loss of consciousness. PMID- 26377479 TI - A Neural Basis for Developmental Topographic Disorientation. AB - Developmental topographic disorientation (DTD) is a life-long condition in which affected individuals are severely impaired in navigating around their environment. Individuals with DTD have no apparent structural brain damage on conventional imaging and the neural mechanisms underlying DTD are currently unknown. Using functional and diffusion tensor imaging, we present a comprehensive neuroimaging study of an individual, J.N., with well defined DTD. J.N. has intact scene-selective responses in the parahippocampal place area (PPA), transverse occipital sulcus, and retrosplenial cortex (RSC), key regions associated with scene perception and navigation. However, detailed fMRI studies probing selective tuning properties of these regions, as well as functional connectivity, suggest that J.N.'s RSC has an atypical response profile and an atypical functional coupling to PPA compared with human controls. This deviant functional profile of RSC is not due to compromised structural connectivity. This comprehensive examination suggests that the RSC may play a key role in navigation related processing and that an alteration of the RSC's functional properties may serve as the neural basis for DTD. SIGNIFICANCE STATEMENT: Individuals with developmental topographic disorientation (DTD) have a life-long impairment in spatial navigation in the absence of brain damage, neurological conditions, or basic perceptual or memory deficits. Although progress has been made in identifying brain regions that subserve normal navigation, the neural basis of DTD is unknown. Using functional and structural neuroimaging and detailed statistical analyses, we investigated the brain regions typically involved in navigation and scene processing in a representative DTD individual, J.N. Although scene-selective regions were identified, closer scrutiny indicated that these areas, specifically the retrosplenial cortex (RSC), were functionally disrupted in J.N. This comprehensive examination of a representative DTD individual provides insight into the neural basis of DTD and the role of the RSC in navigation-related processing. PMID- 26377480 TI - Validation of the Patient Health Questionnaire-9 for Major Depressive Disorder in the Occupational Health Setting. AB - Purpose Because of the increased risk of long-term sickness leave for employees with a major depressive disorder (MDD), it is important for occupational health professionals to recognize depression in a timely manner. The Patient Health Questionnaire-9 (PHQ-9) has proven to be a reliable and valid instrument for screening MDD, but has not been validated in the occupational health setting. The aim of this study was to validate the PHQ-9 for MDD within a population of employees on sickness leave by using the MINI-International Neuropsychiatric Interview (MINI) as a gold standard. Methods Participants were recruited in collaboration with the occupational health service. The study sample consisted of 170 employees on sickness leave between 4 and 26 weeks who completed the PHQ-9 and were evaluated with the MINI by telephone. Sensitivity, specificity, positive and negative predictive value, efficiency and 95 % confidence intervals (95 % CIs) were calculated for all possible cut-off values. A receiver operator characteristics (ROC) analysis was computed for PHQ-9 score versus the MINI. Results The optimal cut-off value of the PHQ-9 was 10. This resulted in a sensitivity of 86.1 % [95 % CI (69.7-94.8)] and a specificity of 78.4 % [95 % CI (70.2-84.8)]. Based on the ROC analysis, the area under the curve for the PHQ-9 was 0.90 [SE = 0.02; 95 % CI (0.85-0.94)]. Conclusion The PHQ-9 shows good sensitivity and specificity as a screener for MDD within a population of employees on sickness leave. PMID- 26377482 TI - Solvent-Controlled C2/C5-Regiodivergent Alkenylation of Pyrroles. AB - A solvent-controlled C2/C5-selective alkenylation of 3,4-disubstituted pyrroles has been developed. The C3 substituent of pyrroles proved crucial to the regioselectivity. Substrates bearing directing groups at the C3 position exhibited excellent C2-selectivities in chelation-assisted C?H activation in toluene or 1,4-dioxane. However, a DMSO/DMF solvent system could override the chelation effect of weak directing groups, such as carboxylate and carbonyl groups, favoring instead regioselectivity towards the more electron-rich C5 position. A series of 3-carboxylate and 3-carbonyl pyrroles were tested and showed moderate to good yields with good regioselectivities for both C2- and C5 alkenylation process. PMID- 26377483 TI - Separation of cobalt and nickel using a thermomorphic ionic-liquid-based aqueous biphasic system. AB - A [P44414][Cl]-NaCl-H2O ionic liquid-based aqueous biphasic system shows promising results for the separation of cobalt(II) and nickel(II) by homogeneous liquid-liquid extraction. The extracting phase consists of a hydrophilic ionic liquid that is salted-out by sodium chloride, indicating that there is no need for using hydrophobic ionic liquids. PMID- 26377481 TI - The effect of the water soluble fraction of crude oil on survival, physiology and behaviour of Caspian roach, Rutilus caspicus (Yakovlev, 1870). AB - The water soluble fraction (WSF) of crude oil is a complex and toxic mixture of hydrocarbons that aquatic organisms directly encounter in oil spills. WSF plays an important role in the toxicity of crude oil to aquatic organisms. In the present study, the effects of WSF on juvenile Caspian roach, Rutilus caspicus, at lethal and sub-lethal level was investigated. The lethality of WSF on R. caspicus was studied by conducting 96h LC50 tests with semi-static exposure methods with 6 and 24h solution renewals. The 96h LC50 of WSF was estimated at 62.5% and 35.9% WSF concentrations for 24h and 6h renewal methods, respectively. To investigate the sub-lethal effect of WSF on R. caspicus, fish were exposed to 62.5, 31.3, and 6.3% concentrations of WSF for 24h and changes in their respiration rate and swimming activity was monitored during the exposure. At the end of the exposure period, four hematologic parameters [O2 and CO2 pressures (pO2 and pCO2), hematocrit, and hemoglobin content] of the fish were measured. The result of the behavioural experiment revealed that all three studied concentrations of WSF elevated the respiration rate and reduced the swimming activity of R. caspicus. No significant changes were detected in the hematocrit and hemoglobin content of the fish blood, but the blood pO2 of the fish exposed to 62.5% WSF decreased while the blood pCO2 increased. The results of this study suggest that the egression of the volatile components in hydrocarbon mixtures during conventional semi-static toxicity tests may lead to underestimating the toxicity of the hydrocarbons. The results of the sub-lethal experiments propose that failure of the respiratory system that leads to asphyxia may be a major mechanism that results in lethal effect of WSF in high concentrations. PMID- 26377484 TI - Quantification of 16 polycyclic aromatic hydrocarbons in cigarette smoke condensate using stable isotope dilution liquid chromatography with atmospheric pressure photoionization tandem mass spectrometry. AB - A stable isotope dilution liquid chromatography tandem mass spectrometry method for the analysis of 16 polycyclic aromatic hydrocarbons in cigarette smoke condensate was developed and validated. Compared with previously reported methods, this method has lower limits of detection (0.04-1.35 ng/cig). Additionally, the proposed method saves time, reduces the number of separation steps, and reduces the quantity of solvent needed. The new method was applied to evaluate polycyclic aromatic hydrocarbon content in 213 commercially available cigarettes in China, under the International Standardization Organization smoking regime and the Health Canadian intense smoking regime. The results showed that the total polycyclic aromatic hydrocarbon content was more than two times higher in samples from the Health Canadian intense smoking regime than in samples from the International Standardization Organization smoking regime (1189.23 versus 2859.50 ng/cig, p < 0.05). Meanwhile, the concentration of individual polycyclic aromatic hydrocarbons (and total polycyclic aromatic hydrocarbons) increased with labeled tar content in both of the tested smoking regimes. There was a positive correlation between total polycyclic aromatic hydrocarbons under the International Standardization Organization smoking regime with that under the Health Canadian intense smoking regime. The proposed liquid chromatography tandem mass spectrometry method is satisfactory for the rapid, sensitive, and accurate quantitative evaluation of polycyclic aromatic hydrocarbon content in cigarette smoke condensate, and it can be applied to assess potential health risks from smoking. PMID- 26377486 TI - Combined near-infrared excited SEHRS and SERS spectra of pH sensors using silver nanostructures. AB - Surface-enhanced hyper-Raman scattering (SEHRS) and surface-enhanced Raman scattering (SERS) of para-mercaptobenzoic acid (pMBA) were studied with an excitation wavelength of 1064 nm, using different silver nanostructures as substrates for both SEHRS and SERS. The spectra acquired for different pH values between pH 2 and pH 12 were compared with SERS data obtained from the identical samples at 532 nm excitation. Comparison of the ratios of the enhancement factors from SEHRS and SERS experiments with those from calculations using plasmonic absorbance spectra suggests that the difference between total surface-enhancement factors of SEHRS and SERS for pMBA is mainly explained by a difference between the electromagnetic contributions for linear and non-linear SERS. SERS and SEHRS spectra obtained at near-infrared (NIR) excitation indicate an overall reduction of enhancement by a factor of 2-3 at very low and very high pH, compared to neutral pH. Our data provide evidence that different molecular vibrations and/or different adsorption species are probed in SERS and SEHRS, and that SEHRS is very sensitive to slight changes in the pMBA-nanostructure interactions. We conclude that the combination of SEHRS and SERS using NIR excitation is more powerful for micro-environmental pH sensing than one-photon spectra excited in the visible range alone. PMID- 26377485 TI - The Mutation Profile of Calreticulin in Patients with Myeloproliferative Neoplasms and Acute Leukemia. AB - OBJECTIVE: Calreticulin (CALR) plays important roles in cell proliferation, apoptosis, and immune responses. CALR mutations were described recently in Janus kinase 2 gene (JAK2)-negative or MPL-negative primary myelofibrosis (PMF) and essential thrombocythemia (ET) patients. CALR trails JAK2 as the second most mutated gene in myeloproliferative neoplasms (MPNs). However, little is known about CALR mutation in Chinese patients with leukemia. In the present study, a cohort of 305 Chinese patients with hematopoietic neoplasms was screened for CALR mutations, with the aim of uncovering the frequency of CALR mutations in leukemia and MPNs. MATERIALS AND METHODS: Polymerase chain reaction and direct sequencing were performed to analyze mutations of CALR in 305 patients with hematopoietic malignancies, including 135 acute myeloid leukemia patients, 57 acute lymphoblastic leukemia patients, and 113 MPN patients. RESULTS: CALR mutations were found in 10.6% (12 of 113) of samples from patients with MPNs. CALR mutations were determined in 11.3% (6 of 53), 21.7% (5 of 23), and 9.1% (1/11) of patients with ET, PMF, and unclassifiable MPN, respectively. CONCLUSION: We showed that MPN patients carrying CALR mutations presented with higher platelet counts and lower hemoglobin levels compared to those with mutated JAK2. However, all of the leukemia patients had negative results for CALR mutations. PMID- 26377487 TI - Bypasses in intracellular glucose metabolism in iron-limited Pseudomonas putida. AB - Decreased biomass growth in iron (Fe)-limited Pseudomonas is generally attributed to downregulated expression of Fe-requiring proteins accompanied by an increase in siderophore biosynthesis. Here, we applied a stable isotope-assisted metabolomics approach to explore the underlying carbon metabolism in glucose grown Pseudomonas putida KT2440. Compared to Fe-replete cells, Fe-limited cells exhibited a sixfold reduction in growth rate but the glucose uptake rate was only halved, implying an imbalance between glucose uptake and biomass growth. This imbalance could not be explained by carbon loss via siderophore production, which accounted for only 10% of the carbon-equivalent glucose uptake. In lieu of the classic glycolytic pathway, the Entner-Doudoroff (ED) pathway in Pseudomonas is the principal route for glucose catabolism following glucose oxidation to gluconate. Remarkably, gluconate secretion represented 44% of the glucose uptake in Fe-limited cells but only 2% in Fe-replete cells. Metabolic (13) C flux analysis and intracellular metabolite levels under Fe limitation indicated a decrease in carbon fluxes through the ED pathway and through Fe-containing metabolic enzymes. The secreted siderophore was found to promote dissolution of Fe-bearing minerals to a greater extent than the high extracellular gluconate. In sum, bypasses in the Fe-limited glucose metabolism were achieved to promote Fe availability via siderophore secretion and to reroute excess carbon influx via enhanced gluconate secretion. PMID- 26377488 TI - Hypervolemic hypernatremia is the most common type of hypernatremia in the intensive care unit. AB - BACKGROUND: A high incidence of hypervolemic hypernatremia has been described in patients recovering from acute kidney injury (AKI) in intensive care units. However, this has been limited to only a few cases. METHODS: One hundred fifty adult patients recovering from AKI in the intensive care unit of a single institution during a 6-year period, who developed hypernatremia during the course of their illness, were investigated. Serum and urine electrolytes, osmolality, urea nitrogen and creatinine were measured. The weights of these patients at the time of hypernatremia development and at presentation to the hospital were also measured. RESULTS: Even though the hypernatremia was mild in most patients (146 160 mEq/L), the average rise in serum sodium concentration was 14.5 +/- 7.1 mEq/L. Of the 34 patients who had all urinary studies available, the average urine osmolality was 436 +/- 128 mmol/kg of which 172 +/- 54 mmol/L was contributed by sodium, potassium and their accompanying anion. Another 204 +/- 96 mmol/L was accounted for by urea and creatinine (mainly urea). Almost all the patients had hypervolemia as evidenced by the presence of edema and an average weight gain of more than 9 +/- 11 kg between the time of presentation and the onset of hypernatremia despite likely having lost muscle mass from being in the intensive care unit for several days. The weight data were available in 54 patients, and only eight of these patients had lost weight at the time of the development of hypernatremia. CONCLUSION: Hypervolemic hypernatremia is by far the most common cause of hypernatremia in patients in the intensive care unit. Even though the patients are in negative fluid balance at the time of the development of the hypernatremia, earlier saline administration has caused massive volume overload despite the ongoing losses. Post-AKI diuresis in the face of inability to maximally concentrate the urine because of renal failure often leads to mainly mild elevations in serum sodium concentration. The urine solute is mainly urea because of the often high serum urea concentrations with little electrolytes being present in the urine. PMID- 26377489 TI - Pro and con arguments in using alternative dialysis regimens in the frail and elderly patients. AB - In the last decade, an increasing number of patients over 75 years of age are starting renal replacement therapy. Frailty is highly prevalent in elderly patients with end-stage renal disease (ESRD) in the context of the increased prevalence of some ESRD-associated conditions: protein-energy wasting, inflammation, anaemia, acidosis or hormonal disturbances. There are currently no hard data to support guidance on the optimal duration of dialysis for frail/elderly ESRD patients. The current debate is not about starting dialysis or managing conservatory frail ESRD patients, but whether a more intensive regimen once dialysis is initiated (for whatever reasons and circumstances) would improve patients' outcome. The most important issue is that all studies performed with extended/alternative dialysis regimens do not specifically address this particular type of patients and therefore all the inferences are derived from the general ESRD population. Care planning should be responsive to end-of-life needs whatever the treatment modality. Care in this setting should focus on symptom control and quality of life rather than life extension. We conclude that, similar to the general dialysed population, extensive application of more intensive dialysis schedules is not based on solid evidence. However, after a thorough clinical evaluation, a limited period of a trial of intensive dialysis could be prescribed in more problematic patients. PMID- 26377490 TI - Sildenafil activates antioxidant and antiapoptotic genes and inhibits proinflammatory cytokine genes in a rat model of renal ischemia/reperfusion injury. AB - OBJECTIVES: To study the possible renoprotective effect of sildenafil against renal ischemia/reperfusion (I/R) injury and its effect on the expression of some antioxidant, antiapoptotic gene and proinflammatory cytokine genes in rat model of renal I/R injury. MATERIALS AND METHODS: One hundred and twenty male Sprague Dawley rats were subdivided into three equal groups: sham (underwent right nephrectomy without ischemia), control (underwent right nephrectomy and left ischemia for 45 min) and study [as control with 1 mg/kg sildenafil (per oral) 60 min before anesthesia]. Serum creatinine and BUN were measured at the baseline and the study endpoints (2, 24, 48 h and 7 days), and the left kidney was harvested at study endpoints for histopathological examination as well as for assessment of the expression of antioxidant genes (Nrf-2, HO-1 and NQO-1), antiapoptotic gene (Bcl-2) and inflammatory cytokines, e.g., TNF-a, IL-1beta and ICAM-1. RESULTS: I/R caused significant increase in serum creatinine, BUN, histopathological damage score (p < 0.001) and significant reduction in antioxidant genes (nrf2, HO-1 and NQO-1) and antiapoptotic gene (Bcl2) with significant increase in TNF-a, IL-1beta and ICAM-1 genes in kidney tissues. Pretreatment with sildenafil caused significant attenuation of serum creatinine and BUN as well as significant increase in the expression of antioxidant genes and Bcl-2 genes with significant reduction in the expression of proinflammatory cytokine genes (p value < 0.001). CONCLUSION: The renoprotective effect of sildenafil against renal I/R might be due to the activation of antioxidant genes (Nrf2, HO-1 and NQO-1) and antiapoptotic gene (Bcl2) and attenuation of proinflammatory cytokines (TNF-a, IL-1beta and ICAM-1). PMID- 26377491 TI - Possible impact of continuous drainage after minimally invasive partial nephrectomy. AB - PURPOSE: Postoperative management of minimally invasive partial nephrectomy (MIPN) without drain placement is common, but the effects on patients are unclear. We investigated the impact of no drain placement after MIPN. METHODS: We retrospectively studied 194 consecutive patients who underwent laparoscopic and robotic partial nephrectomy at one academic center. The study group included 46 evaluable patients without drain placement. The quantity of postoperative fluid collection in the perirenal space was calculated using computed tomography. The preoperative and postoperative serum concentrations of total protein, albumin, neutrophils, lymphocytes, monocytes numbers, and C-reactive protein (CRP) levels in the blood were compared between groups. RESULTS: Drains were placed in 148 (76.3 %) patients who underwent MIPN. The remaining 46 (23.7 %) patients did not have drain placement. Although the average total quantity of fluid discharged from the drain was 214 mL, the average fluid remaining in the perirenal space did not significantly differ with or without drain placement (20.3 vs. 16.8 mL, p = 0.64). The decrease in serum total protein and albumin was significantly greater with drain placement than without (total protein: 18.9 vs. 12.2 %, p < 0.001; and albumin: 24.7 vs. 22 %, p = 0.038). No drain placement also caused markedly greater decreases in lymphocytes and monocytes than did drain placement, whereas neutrophils and CRP did not differ based on drain placement. CONCLUSION: Analysis of the quantity of fluid collection showed little need for routine drain placement. Not placing a drain after MIPN prevented serum protein loss and possibly accelerated wound-healing immune responses. PMID- 26377493 TI - Drains in urology: an unnecessary habit. PMID- 26377492 TI - Survival after parathyroidectomy in chronic hemodialysis patients with severe secondary hyperparathyroidism. AB - INTRODUCTION: The life for end-stage renal disease patients has remarkably improved in the last years. Although mineral and bone disorders remain as unsolved complication, in severe secondary hyperparathyroidism (sHPT), the ultimate treatment is parathyroidectomy (PTX). It is an old treatment, but there are still insufficient data regarding survival after PTX. The study goals were to compare 2-year mortality and morbidity after PTX in surgically versus medically treated sHPT and to compare the efficacy and safety in subtotal versus total PTX in a cohort of patients receiving hemodialysis (HD). METHODS: This prospective, longitudinal study was carried out on a cohort of chronic HD patients with severe sHPT (iPTH over 700 pg/ml). Among the overall HD population, 26 patients underwent PTX. This group was compared to a control group treated with specific drugs. Laboratory parameters, specific symptoms and mortality were registered after 24 months of follow-up for each group. The subgroups of subtotal and total PTX patients were also compared. RESULTS: All average values of mineral markers were significantly reduced after PTX, as a proof that surgical treatment was effective. The reduction in mineral markers and the improvement in symptoms and mortality rates were similar after total and subtotal PTX. Bone pain was significantly lower in patients after PTX than in those drug treated (p = 0.0005), but not muscle weakness and itching. Survival at 2 years was better in patients surgically treated (PTX) despite significantly higher mean baseline values of iPTH, Ca and ALP compared to patients medically treated (p = 0.03). CONCLUSIONS: We compared clinical and laboratory outcomes in HD patients with severe sHPT. Mortality, bone pain and mineral markers were improved by PTX. Total and subtotal PTX had similar clinical outcomes. PMID- 26377494 TI - Prevalence of chronic kidney disease and its association with cardio-metabolic risk factors in the adult Romanian population: the PREDATORR study. AB - PURPOSE: PREDATORR is the first national study analyzing the prevalence of chronic kidney disease and its prognosis and association with socio-demographic, cardio-metabolic and lifestyle risk factors in the adult Romanian population. METHODS: Chronic kidney disease was defined according to the KDIGO 2012 criteria as an estimated glomerular filtration rate <60 mL/min/1.73 m(2) and/or urinary albumin-to-creatinine ratio >=30 mg/g. The socio-demographic, lifestyle and anamnestic data were collected through interviewer-administered questionnaires. Physical examination and biochemical assays were also performed. RESULTS: This cross-sectional study conducted between December 2012 and February 2014 in Romania included 2717 adults. The overall age- and sex-adjusted prevalence of chronic kidney disease was 6.74 % (95 %CI 5.60-7.88 %), of which 3.31 % (2.50 4.13 %) had only reduced kidney function (estimated glomerular filtration rate <60 mL/min/1.73 m(2)), 2.98 % (2.21-3.76 %) had only albuminuria, and 0.45 % (0.14-0.74 %) had both. The prevalence of chronic kidney disease increased with age and was similar in women and in men. Age, hyperuricemia, impaired glucose regulation (diabetes/prediabetes), hypertriglyceridemia and a family history of renal disease were independent risk factors for the presence of chronic kidney disease. CONCLUSIONS: The PREDATORR study showed a high prevalence of chronic kidney disease in the adult Romanian population providing data on its prognosis and association with several cardio-metabolic risk factors. PMID- 26377495 TI - Concomitant Gleason Score >= 7 prostate cancer is an independent prognosticator for poor survival in nonmetastatic bladder cancer patients undergoing radical cystoprostatectomy. AB - PURPOSE: In bladder cancer (BCa) patients undergoing radical cystoprostatectomy (RCPx), concomitant prostate cancer (PCa) is a common finding. Up to now there is no clear evidence to suggest that concomitant PCa is a predictor of outcome in these patients. Aim of this study was to assess incidence and clinicopathologic characteristics of concomitant PCa in RCPx specimen and correlate it to survival parameters from a single-centre material over two decades. METHODS: All men who had undergone RCPx for BCa at our institution between 1994 and 2013 were included in this study. Clinicopathologic parameters for BCa and PCa were evaluated and correlated with outcome parameters. Survival analysis was performed for the subgroup of nonmetastatic organ-confined BCa to evaluate the role of concomitant Gleason Score (GS) >=7 PCa. RESULTS: Of 945 men who had undergone RCPx for BCa, concomitant PCa was present in 237 patients (25.1 %). There was a significant increase in PCa incidence from 18.9 to 32.3 % between 1994 and 2013 (p = 0.009). Concomitant PCa represented a more aggressive phenotype at the end of the study (p = 0.037). In nonmetastatic organ-confined BCa, concomitant GS >=7 PCa (HR 3.09; p = 0.0001) and age > 68 (HR 1.80; p = 0.0004) were independent negative predictors for overall survival. CONCLUSIONS: Concomitant PCa in RCPx specimen of BCa patients is a common finding. The incidence of concomitant PCa has significantly increased within 2 decades, presenting a more aggressive phenotype. Age and in particular concomitant GS >=7 PCa are independent prognosticators for poor survival in patients with nonmetastatic organ-confined BCa. PMID- 26377496 TI - Behavioral measures to reduce non-adherence in renal transplant recipients: a prospective randomized controlled trial. AB - PURPOSE: Solid-organ transplant recipients present a high rate of non-adherence to drug treatment. Few interventional studies have included approaches aimed at increasing adherence. The objective of this study was to evaluate the impact of an educational and behavioral strategy on treatment adherence of kidney transplant recipients. METHODS: In a randomized prospective study, incident renal transplant patients (n = 111) were divided into two groups: control group (received usual transplant patient education) and treatment group (usual transplant patient education plus ten additional weekly 30-min education/counseling sessions about immunosuppressive drugs and behavioral changes). Treatment adherence was assessed using ITAS adherence questionnaire after 3 months. Renal function at 3, 6, and 12 months, and the incidence of transplant rejection were evaluated. RESULTS: The non-adherence rates were 46.4 and 14.5 % in the control and treatment groups (p = 0.001), respectively. The relative risk for non-adherence was 2.59 times (CI 1.38-4.88) higher in the control group. Multivariate analysis demonstrated a 5.84 times (CI 1.8-18.8, p = 0.003) higher risk of non-adherence in the control group. There were no differences in renal function and rejection rates between groups. CONCLUSIONS: A behavioral and educational strategy addressing the patient's perceptions and knowledge about the anti-rejection drugs significantly improved the short-term adherence to immunosuppressive therapy. PMID- 26377498 TI - Annuloplasty Ring Selection in Ischemic Mitral Regurgitation for Valve Repair During Coronary Artery Bypass Grafting. PMID- 26377499 TI - Hereditary Elliptocytosis with Pyropoikilocytosis. PMID- 26377497 TI - The effects of hypnotherapy during transrectal ultrasound-guided prostate needle biopsy for pain and anxiety. AB - INTRODUCTION: Several studies evaluating the tolerance of transrectal ultrasound (TRUS)-guided needle biopsies showed that moderate-to-severe pain was associated with the procedure. Additionally, prebiopsy anxiety or rebiopsy as a result of a prior biopsy procedure is mentioned as factors predisposing to higher pain intensity. Thus, in this study, we investigated the effects of hypnotherapy during transrectal ultrasound-guided prostate needle biopsy for pain and anxiety. MATERIALS AND METHODS: Sixty-four patients presenting for TRUS-guided prostate needle biopsy were randomly assigned to receive either 10-min presurgery hypnosis session (n = 32, mean age 63.5 +/- 6.1, p = 0.289) or a presurgery control session (n = 32, mean age 61.8 +/- 6.8, p = 0.289). The hypnosis session involved suggestions for increased relaxation and decreased anxiety. Presurgery pain and anxiety were measured using visual analog scales (VAS), Beck Anxiety Inventory (BAI), and Hamilton Anxiety Scale (HAS), respectively. In our statistics, p < 0.05 was considered statistically significant. RESULTS: Postintervention, and before surgery, patients in the hypnosis group had significantly lower mean values for presurgery VAS [mean 1 (0-8); p = 0.011], BAI (6.0 vs 2.0; p < 0.001), and HAS (11.0 vs 6.0; p < 0.001). CONCLUSION: The study results indicate that a brief presurgery hypnosis intervention can be an effective means of controlling presurgical anxiety, and therefore pain, in patients awaiting diagnostic prostate cancer surgery. PMID- 26377500 TI - Introducing Viewpoints in The Journal of Physical Chemistry A/B/C. PMID- 26377501 TI - The 70th International Symposium on Molecular Spectroscopy. PMID- 26377502 TI - Do neighbourhood socioeconomic circumstances not matter for weight status among Australian men? Multilevel evidence from a household survey of 14 691 adults. AB - OBJECTIVE: A recent analysis of the Australian National Health Survey (2011-2012) reported that the patterning of overweight and obesity among men, unlike for women, was not associated with neighbourhood socioeconomic disadvantage. The purpose of this study was to examine whether this gender difference in potential neighbourhood 'effects' on adult weight status can be observed in analyses of a different source of data. DESIGN, SETTING AND PARTICIPANTS: A cross-sectional sample of 14 693 people aged 18 years or older was selected from the 2012 wave of the 'Household, Income and Labour Dynamics in Australia' (HILDA). Three person level outcomes were considered: (1) body mass index (BMI); (2) a binary indicator of 'normal weight' versus 'overweight or obese'; and (3) 'normal weight or overweight' versus 'obese'. Area-level socioeconomic circumstances were measured using quintiles of the Socio Economic Index For Areas (SEIFA). Multilevel linear and logistic regression models were used to examine associations while accounting for clustering within households and neighbourhoods, adjusting for person-level socioeconomic confounders. RESULTS: Neighbourhood-level factors accounted for 4.9% of the overall variation in BMI, whereas 20.1% was attributable to household level factors. Compared with their peers living in deprived neighbourhoods, mean BMI was 0.7 kg/m(2) lower among men and 2.2 kg/m(2) lower among women living in affluent areas, with a clear trend across categories. Similarly, the percentage of overweight and obese, and obesity specifically, was lower in affluent areas for both men and women. These results were robust to adjustment for confounders. CONCLUSIONS: Unlike findings from the national health survey, but in line with evidence from other high-income countries, this study finds an inverse patterning of BMI by neighbourhood disadvantage for men, and especially among women. The potential mediators which underpin this gender difference in BMI within disadvantaged neighbourhoods warrant further investigation. PMID- 26377503 TI - Factors influencing obesogenic dietary intake in young children (0-6 years): systematic review of qualitative evidence. AB - BACKGROUND: Obesogenic dietary intake is prevalent in young children and is associated with obesity and other adverse health outcomes in childhood and later in life. OBJECTIVE: To describe the barriers to and facilitators of obesogenic dietary intake in early childhood, in order to inform interventions and public health policies to prevent obesity. DESIGN: Systematic review of qualitative literature on factors influencing obesogenic diets in children aged 0-6 years. DATA SOURCES: MEDLINE, EMBASE, CINAHL, PsycINFO, Web of Knowledge, British Nursing Index, ASSIA and Sociological Abstracts. REVIEW METHODS: Qualitative studies meeting the inclusion criteria were synthesised. Data were analysed by creating a thematic framework, underpinned by the socioecological model, which included familiarisation of data across the studies, indexing, charting, mapping and interpretation. RESULTS: 20 studies from the USA (10), Europe (6) and Australia (4) included the views of 1067 participants (901 parents/caregivers, 37 children, 87 teachers, 15 dieticians and 27 nursery staff). Study designs included focus groups (n=16), individual interviews (n=6) and ethnography (n=1) with some studies using more than one design. Despite wide differences in the study context and focus, several consistent themes emerged. Parental factors increasing young children's obesogenic diets were: negative parent/family/peer modelling, lack of knowledge, time constraints, using food as reward, affordability and concerns about child's health. Child preferences also increased intake. Environmental factors increasing intake include: availability, advertising, societal, cultural and preschool/childcare influences. CONCLUSIONS: Future intervention strategies should aim to promote modelling of positive behaviours, create home and preschool environments that promote healthy diets, and simultaneously target factors at the family and preschool/childcare levels. TRIAL REGISTRATION NUMBER: This review is one of a series of systematic reviews on the determinants of obesogenic behaviours in young children, registered with the International Prospective Register for Systematic Reviews (PROSPERO), CRD42012002881. PMID- 26377504 TI - Older people, the natural environment and common mental disorders: cross sectional results from the Cognitive Function and Ageing Study. AB - OBJECTIVES: To explore the hypothesis that higher exposure to natural environments in local areas is associated with a lower odds of depression and anxiety in later life. DESIGN: A cross-sectional study based on the year-10 interview of the Medical Research Council Cognitive Function and Ageing Study (CFAS), a population-based study of ageing in the UK. Postcodes of the CFAS participants were mapped onto small geographic units, lower-layer super output areas (LSOAs) and linked to environmental data from government databases. The natural environment was characterised as the percentage of green space and private gardens in each LSOA based on the UK Generalised Land Use 2001 Dataset. PARTICIPANTS: 2424 people aged 74 and over in the CFAS year-10 follow-up interview (2001) from 4 English centres (Cambridgeshire, Nottingham, Newcastle and Oxford). MAIN OUTCOME MEASURES: Depression and anxiety; clinical and subthreshold cases were identified using the Geriatric Mental State Examination (GMS) package and its associated diagnostic algorithm: the Automated Geriatric Examination for Computer Assisted Taxonomy. RESULTS: Compared with the lowest quartile, living in the highest quartile of neighbourhood natural environment provision was associated with a reduced odds of subthreshold depression (OR 0.66, 95% CI 0.46 to 0.95), anxiety symptoms (OR 0.62, 95% CI 0.46 to 0.83) and their co-occurrence (OR 0.55, 95% CI 0.35 to 0.84) after adjusting for individual-level factors. Controlling for area deprivation attenuated the strength of associations for subthreshold depression by 20% but not for anxiety symptoms or for co occurrence of the conditions. CONCLUSIONS: A high exposure to natural environments (green space and gardens) in communities was associated with fewer mental disorders among older people. Increasing provision of green environments in local areas could be a potential population-level intervention to improve mental health among older people. PMID- 26377505 TI - Challenges in the use of treatment to investigate cognition. AB - The use of data from people with cognitive impairments to inform theories of cognition is an established methodology, particularly in the field of cognitive neuropsychology. However, it is less well known that studies that aim to improve cognitive functioning using treatment can also inform our understanding of cognition. This paper discusses a range of challenges that researchers face when testing theories of cognition and particularly when using treatment as a tool for doing so. It highlights the strengths of treatment methodology for testing causal relations and additionally discusses how generalization of treatment effects can shed light on the nature of cognitive representations and processes. These points are illustrated using examples from the Special Issue of Cognitive Neuropsychology entitled Treatment as a tool for investigating cognition. PMID- 26377506 TI - The nature of facilitation and interference in the multilingual language system: insights from treatment in a case of trilingual aphasia. AB - The rehabilitation study described here sets out to test the premise of Abutalebi and Green's neurocognitive model--specifically, that language selection and control are components of overall cognitive control. We follow a trilingual woman (first language, L1: Amharic; second language, L2: English; third language, L3: French) with damage to the left frontal lobe and left basal ganglia who presented with cognitive control and naming deficits, through two periods of semantic treatment (French, followed by English) to alleviate naming deficits. The results showed that while the participant improved on trained items, she did not show within- or cross-language generalization. In addition, error patterns revealed a substantial increase of interference of the currently trained language into the nontrained language during each of the two treatment phases. These results are consistent with Abutalebi and Green's neurocognitive model and support the claim that language selection and control are components of overall cognitive control. PMID- 26377507 TI - The mechanics of tessellations - bioinspired strategies for fracture resistance. AB - Faced with a comparatively limited palette of minerals and organic polymers as building materials, evolution has arrived repeatedly on structural solutions that rely on clever geometric arrangements to avoid mechanical trade-offs in stiffness, strength and flexibility. In this tutorial review, we highlight the concept of tessellation, a structural motif that involves periodic soft and hard elements arranged in series and that appears in a vast array of invertebrate and vertebrate animal biomaterials. We start from basic mechanics principles on the effects of material heterogeneities in hypothetical structures, to derive common concepts from a diversity of natural examples of one-, two- and three-dimensional tilings/layerings. We show that the tessellation of a hard, continuous surface - its atomization into discrete elements connected by a softer phase - can theoretically result in maximization of material toughness, with little expense to stiffness or strength. Moreover, the arrangement of soft/flexible and hard/stiff elements into particular geometries can permit surprising functions, such as signal filtering or 'stretch and catch' responses, where the constrained flexibility of systems allows a built-in safety mechanism for ensuring that both compressive and tensile loads are managed well. Our analysis unites examples ranging from exoskeletal materials (fish scales, arthropod cuticle, turtle shell) to endoskeletal materials (bone, shark cartilage, sponge spicules) to attachment devices (mussel byssal threads), from both invertebrate and vertebrate animals, while spotlighting success and potential for bio-inspired manmade applications. PMID- 26377508 TI - A biodegradable adamantane polymer with ketal linkages in its backbone for gene therapy. AB - In this report we present a polyketal, termed pADK, which has adamantane groups embedded in its backbone, and degrades into neutral excretable compounds. pADK was synthesized via click chemistry and had a MW of 49 472 and a PDI of 1.74. We demonstrate here that pADK can increase the transfection efficiency of CD1800 (PEI of 1800 modified beta-cyclodextrin) 60 fold, yet cause no increase in toxicity. PMID- 26377509 TI - Randomized study designs for lifestyle interventions: a tutorial. AB - Unhealthy lifestyle behaviours are considered modifiable risk factors for many diseases. Lifestyle interventions that target these behaviours need rigorous evaluation to assess their effectiveness. The randomized controlled trial is the study design of choice when it comes to the evaluation of interventions. However, lifestyle interventions are often complex and subject to several important issues, such as patient preference and non-adherence, that may threaten the internal and external validity of studies. There is a strong demand for high quality randomized controlled trials of interventions that promote healthy lifestyle behaviours. With this tutorial we aim to provide guidance in the choice of an optimal randomized controlled trial design in future trials of lifestyle interventions. PMID- 26377510 TI - Analysis of Measured and Simulated Supraglottal Acoustic Waves. AB - To date, although much attention has been paid to the estimation and modeling of the voice source (ie, the glottal airflow volume velocity), the measurement and characterization of the supraglottal pressure wave have been much less studied. Some previous results have unveiled that the supraglottal pressure wave has some spectral resonances similar to those of the voice pressure wave. This makes the supraglottal wave partially intelligible. Although the explanation for such effect seems to be clearly related to the reflected pressure wave traveling upstream along the vocal tract, the influence that nonlinear source-filter interaction has on it is not as clear. This article provides an insight into this issue by comparing the acoustic analyses of measured and simulated supraglottal and voice waves. Simulations have been performed using a high-dimensional discrete vocal fold model. Results of such comparative analysis indicate that spectral resonances in the supraglottal wave are mainly caused by the regressive pressure wave that travels upstream along the vocal tract and not by source-tract interaction. On the contrary and according to simulation results, source-tract interaction has a role in the loss of intelligibility that happens in the supraglottal wave with respect to the voice wave. This loss of intelligibility mainly corresponds to spectral differences for frequencies above 1500 Hz. PMID- 26377511 TI - Total Synthesis of (+/-)-Englerin A Using An Intermolecular [3+2] Cycloaddition Reaction of Platinum-Containing Carbonyl Ylide. AB - Total synthesis of (+/-)-Englerin A has been achieved starting from gamma,delta ynone 5 in 14 steps. The key feature of this synthesis is the highly efficient and stereoselective preparation of 8-oxabicyclo[3.2.1]octane derivative 6, a core skeleton of Englerin A, based on an inverse electron-demand [3+2] cycloaddition reaction of the platinum-containing carbonyl ylide, which was developed in our laboratory. PMID- 26377512 TI - Intragroup Variance in Lesbian, Gay, and Bisexual Tobacco Use Behaviors: Evidence That Subgroups Matter, Notably Bisexual Women. AB - INTRODUCTION: Emerging evidence suggests bisexual populations are at increased risk for a variety of negative health outcomes, including tobacco use. Lesbian, gay, and bisexual (LGB) populations are at increased risk for cigarette smoking, but research on LGB subpopulations' use of tobacco products beyond cigarettes and tobacco use differences across LGB subgroups is in its infancy. This study explores differences in use of tobacco products across LGB subgroups, including gender differences among bisexuals. METHODS: This study reports results from a 2013 nationally-representative cross-sectional online survey of US adults (N = 17 087). Weighted tobacco use prevalence and adjusted logistic regression results are reported. RESULTS: LGB populations reported higher current use of any tobacco product (35.7%) and current use of cigarettes (32.0%), e-cigarettes (8.9%), regular (5.5%) and small cigars (11.6%), compared with non-LGB. Bisexual (odds ratio [OR] = 2.6, 95% confidence interval [CI]: 1.7-3.9) and lesbian (OR = 1.7, 95% CI: 1.0-2.7) women have higher odds of any tobacco use than heterosexual women; including greater odds of regular (OR = 2.9, 95% CI: 1.2-7.0 and OR = 2.2, 95% CI: 1.3-3.9; respectively) and small cigar use (OR = 2.4, 95% CI: 1.4-4.1 and OR = 3.2, 95% CI: 2.0-5.1; respectively). Gay men had lower odds of cigar use (OR = 0.4, 95% CI: 0.2-0.8) than heterosexual men. CONCLUSIONS: This is the first US adult population study to assess differences in use of various tobacco products across adult LGB subpopulations and by gender, confirming their increased risk of use and illuminating differences by subgroup and gender. Exploring LGB as a unified population appears inadequate to accurately characterize LGB tobacco use risk. Tobacco-related LGB health inequities, particularly among bisexual and lesbian women, may be greater than previously indicated. IMPLICATIONS: This manuscript provides important contributions to the field of tobacco control and prevention, and more specifically to LGB tobacco-related health disparities research. This is among the first population level studies to explore various tobacco use across LGB populations and across genders, comparing results to non LGB populations in a national study. We provide novel evidence that bisexual women in particular, have a higher risk for use of various tobacco products, compared with other LGB subpopulations. In order to address this disparity, tobacco control professionals need to be made aware of these important differences in tobacco use behavior. PMID- 26377513 TI - Direct-to-Consumer Marketing of Cigar Products in the United States. AB - INTRODUCTION: Although cigar use and sales have increased in the United States over the past decade, little is known about how these products are promoted. Direct-to-consumer (DTC) advertising is a common method used to promote tobacco products and may be a potential channel through which cigars are advertised. METHODS: Comperemedia (Mintel) was used to acquire opt-in direct mail and email advertising for the top 10 cigar brands in the United States between January 2013 and July 2014. The advertisement and corresponding data on brand, advertising spend, and mail volume were downloaded and summarized. Promotions such as coupons, giveaways, and sweepstakes were also examined. RESULTS: A total of 92 unique advertisements met the search criteria and included two brands: Black & Mild (n = 77) and Swisher Sweets (n = 15). Expenditures on direct mail advertising during this period totaled $12 809 630. Black & Mild encompassed 80% of total direct mail volume and 78% of direct mail advertising expenditures. Almost all advertisements contained at least one promotion (88%) and included a URL to the product website (85%). CONCLUSIONS: The results suggest that Black & Mild and Swisher Sweets are the primary cigar brands using DTC advertising. Promotional offers were nearly ubiquitous among the advertisements, which may appeal to price-sensitive populations. Future studies should continue to examine cigar advertising via direct mail and email, in addition to other channels, such as the point-of-sale. IMPLICATIONS: Although cigar use and sales have increased in the United States over the past decade, there is limited data on cigar advertising. This article provides a snapshot of expenditures, volume, and promotional content of DTC cigar advertising in the United States between January 2013 and July 2014. PMID- 26377515 TI - Effects of Electronic Cigarette Liquid Nicotine Concentration on Plasma Nicotine and Puff Topography in Tobacco Cigarette Smokers: A Preliminary Report. AB - INTRODUCTION: Electronic cigarettes (ECIGs) aerosolize a liquid that usually contains propylene glycol and/or vegetable glycerin, flavorants, and the dependence-producing drug nicotine in various concentrations. This study examined the extent to which ECIG liquid nicotine concentration is related to user plasma nicotine concentration in ECIG-naive tobacco cigarette smokers. METHODS: Sixteen ECIG-naive cigarette smokers completed four laboratory sessions that differed by the nicotine concentration of the liquid (0, 8, 18, or 36 mg/ml) that was placed into a 1.5 Ohm, dual coil "cartomizer" powered by a 3.3V battery. In each session, participants completed two, 10-puff ECIG use bouts with a 30-second inter-puff interval; bouts were separated by 60 minutes. Venous blood was sampled before and after bouts for later analysis of plasma nicotine concentration; puff duration, volume, and average flow rate were measured during each bout. RESULTS: In bout 1, relative to the 0mg/ml nicotine condition (mean = 3.8 ng/ml, SD = 3.3), plasma nicotine concentration increased significantly immediately after the bout for the 8 (mean = 8.8 ng/ml, SD = 6.3), 18 (mean = 13.2 ng/ml, SD = 13.2), and 36 mg/ml (mean = 17.0 ng/ml, SD = 17.9) liquid concentration. A similar pattern was observed after bout 2. Average puff duration in the 36 mg/ml condition was significantly shorter compared to the 0mg/ml nicotine condition. Puff volume increased during the second bout for 8 and 18 mg/ml conditions. CONCLUSIONS: For a given ECIG device, nicotine delivery may be directly related to liquid concentration. ECIG-naive cigarette smokers can, from their first use bout, attain cigarette-like nicotine delivery profiles with some currently available ECIG products. IMPLICATIONS: Liquid nicotine concentration can influence plasma nicotine concentration in ECIG-naive cigarette smokers, and, at some concentrations, the nicotine delivery profile of a 3.3V ECIG with a dual coil, 1.5-Ohm cartomizer approaches that of a combustible tobacco cigarette in this population. Finding a product that delivers nicotine as effectively as a tobacco cigarette, as we report here, may be essential for smokers who want to replace completely their combustible tobacco cigarettes with ECIGs. PMID- 26377514 TI - Design and Validation of a Research-Grade Waterpipe Equipped With Puff Topography Analyzer. AB - INTRODUCTION: Worldwide, commercially available waterpipes vary widely in design and durability, including differences in fabrication materials, degree of leak tight fit, and flow path diameter. Little is known about how the components of the waterpipe may influence puffing behavior and user's exposure to toxins. To systematically evaluate exposure, it is necessary to use a standardized research grade waterpipe (RWP) when conducting clinical and laboratory-based trials. METHODS: We developed a RWP that is configured with an in-line topography system which allows real-time measurement and recording of the smoke volume drawn through the RWP. The RWP was calibrated across the flow rate range expected for waterpipe tobacco smoking and the calibration was verified for known puff volumes using a smoking machine. Operation of the RWP was qualified in a cohort of experienced waterpipe smokers, each smoker using the RWP ad libitum in a laboratory setting while smoker topography and subjective effects data were collected. RESULTS: RWP machine smoking was highly reproducible and yielded puff volumes that agreed well with true values. User acceptance was comparable, and puffing behavior was similar in pattern, with more frequent puffing in the beginning of the session, but significantly different in intensity from that used to estimate the majority of toxicant exposure reported in the literature. CONCLUSIONS: The RWP operates with known precision and accuracy and is well accepted by experienced smokers. This tool can be used to determine the extent to which puffing behaviors are affected by the waterpipe design, components, and/or accessories, tobacco nicotine content, sweet flavorings and/or additives known to increase addictiveness. IMPLICATIONS: This study describes a standardized RWP, equipped with a puffing topography analyzer, which can operate with known precision and accuracy, and is well-accepted by experienced smokers in terms of satisfaction and reward. The RWP is an important tool for determining if puffing behaviors, and thus estimated toxin exposures, are affected by the waterpipe design, components, and/or accessories, tobacco nicotine content, sweet flavorings, and/or additives that are known to increase addictiveness. PMID- 26377516 TI - Predictive and External Validity of a Pre-Market Study to Determine the Most Effective Pictorial Health Warning Label Content for Cigarette Packages. AB - INTRODUCTION: Studies examining cigarette package pictorial health warning label (HWL) content have primarily used designs that do not allow determination of effectiveness after repeated, naturalistic exposure. This research aimed to determine the predictive and external validity of a pre-market evaluation study of pictorial HWLs. METHODS: Data were analyzed from: (1) a pre-market convenience sample of 544 adult smokers who participated in field experiments in Mexico City before pictorial HWL implementation (September 2010); and (2) a post-market population-based representative sample of 1765 adult smokers in the Mexican administration of the International Tobacco Control Policy Evaluation Survey after pictorial HWL implementation. Participants in both samples rated six HWLs that appeared on cigarette packs, and also ranked HWLs with four different themes. Mixed effects models were estimated for each sample to assess ratings of relative effectiveness for the six HWLs, and to assess which HWL themes were ranked as the most effective. RESULTS: Pre- and post-market data showed similar relative ratings across the six HWLs, with the least and most effective HWLs consistently differentiated from other HWLs. Models predicting rankings of HWL themes in post-market sample indicated: (1) pictorial HWLs were ranked as more effective than text-only HWLs; (2) HWLs with both graphic and "lived experience" content outperformed symbolic content; and, (3) testimonial content significantly outperformed didactic content. Pre-market data showed a similar pattern of results, but with fewer statistically significant findings. CONCLUSIONS: The study suggests well-designed pre-market studies can have predictive and external validity, helping regulators select HWL content. PMID- 26377517 TI - Master Settlement Agreement Compliance Tobacco Directories: A Tool to Track Tribally Manufactured Cigarettes. AB - INTRODUCTION: Little is known about the scope of the tribally manufactured cigarette market. This study illuminates the topic by examining the Master Settlement Agreement Compliance Tobacco Directories, regularly updated documents that list the cigarette manufacturers and brand families that can be legally sold within participating states. METHODS: In July 2014, the latest Tobacco Directories were identified for 43 states and the District of Columbia. Colorado archival tobacco directories were extracted, by month since 2003. Tribal manufacturers and brands were identified in the directories and mapped by state. RESULTS: A total of 11 tribal manufacturers and 39 tribal cigarette brand families were identified in publicly available tobacco directories. Total unique brands were tallied by state, ranging from 1 to 24 unique brands. Historical data from Colorado showed that tribal manufacturers, as a percentage of all manufacturers, increased from 3.2% in 2003 to 20.6% by mid-2014. DISCUSSION: Analysis of Tobacco Directories offers an innovative approach to better understand the tribally manufactured cigarette market. More research is needed to understand reporting and compliance to the Tobacco Directories by manufacturers and retailers, and their usefulness as a research tool to the tobacco control community. IMPLICATIONS: This study aims to make three contributions to the literature: (1) identify tribal tobacco manufacturers and brands in the Master Settlement Agreement Compliance documents; (2) highlight the presence and scope of the tribally manufactured cigarette brands across the United States; and (3) observe any upward or downward trends in tobacco brands and manufacturers since the directories' implementation. PMID- 26377518 TI - Electronic Cigarettes: Awareness, Recent Use, and Attitudes Within a Sample of Socioeconomically Disadvantaged Australian Smokers. AB - INTRODUCTION: Electronic cigarette (e-cigarette) awareness, trial of e-cigarettes in the past 12 months, source and perceptions of safety and effectiveness was assessed within a disadvantaged sample of adult Australian smokers receiving welfare aid. METHODS: A cross-sectional survey was administered to clients who smoke at two community service organizations in New South Wales, Australia from October 2013 to July 2014. E-cigarette awareness, trial in past 12 months, sources of e-cigarettes and perceptions of the safety and effectiveness of e cigarettes to help people quit were assessed along with sociodemographic and smoking-related variables. RESULTS: In total, 369 participants completed the survey (77% response rate). Awareness and trial of e-cigarettes were reported by 77% (n = 283) and 35% (n = 103) of the sample, respectively. E-cigarettes were most commonly obtained from friends/strangers followed by tobacco shops (tobacconists). Trying e-cigarettes in the past 12 months was significantly associated with positive perceptions of their safety (odds ratio [OR] = 1.8, 95% confidence interval [CI] = 1, 3.1) and effectiveness (OR = 1.9, 95% CI = 1.1, 3.2). Motivation to quit tobacco smoking was also significantly positively associated with positive perceptions of e-cigarette safety (OR = 1.2, 95% CI = 1.1, 1.4) and effectiveness (OR = 1.2, 95% CI = 1.0, 1.3). CONCLUSIONS: Rates of awareness and trial of e-cigarettes within a disadvantaged sample of Australian smokers are comparable to rates found within representative samples of the general Australian population. Previously trying e-cigarettes and higher levels of motivation to quit were associated with more positive perceptions of e cigarette safety and effectiveness. IMPLICATIONS: This study demonstrates that socioeconomically disadvantaged smokers are aware of and accessing e-cigarettes in a country with relatively high restrictions covering e-cigarette sale and use. PMID- 26377519 TI - Urinary Cotinine Levels Among Latino Tobacco Farmworkers in North Carolina Compared to Latinos Not Employed in Agriculture. AB - INTRODUCTION: This analysis describes urinary cotinine levels of North Carolina Latino farmworkers, compares cotinine levels of farmworkers to those of Latinos non-farmworkers, determines factors associated with farmworker cotinine levels, and determines if differences in farmworker and non-farmworker cotinine levels are associated with smoking. METHODS: Data are from 63 farmworkers and 44 non farmworkers who participated in a larger study of occupational exposures. Questionnaire data and urine samples collected in 2012 and 2013 are analyzed. RESULTS: Farmworkers had urinary cotinine levels that were far greater than the non-farmworker group. Geometric mean (GM) urinary cotinine levels for farmworkers were 1808.22ng/ml in 2012, and 396.03ng/ml in 2013; corresponding GM levels for non-farmworkers were 4.68ng/ml and 9.03ng/ml. Farmworker GM cotinine levels were associated with harvesting tobacco (1242.77ng/ml vs. 471.26ng/ml; P = .0048), and working in wet shoes (1356.41ng/ml vs. 596.93ng/ml; P = .0148). Smoking did not account for cotinine level differences; the GM cotinine level for farmworkers who did not smoke was 541.31ng/ml; it was 199.40ng/ml for non-farmworkers who did smoke. CONCLUSION: North Carolina farmworkers experience large nicotine doses. The long-term health effects of these doses are not known. Although procedures to reduce occupational nicotine exposure are known, no changes in work practices or in policies to protect workers have been implemented. Research on the health effects of occupational nicotine exposure must become a priority. Current knowledge of occupational transdermal nicotine exposure must be used to improve occupational safety practice and policy for tobacco workers. IMPLICATIONS: This study documents the heavy burden of nicotine exposure and dose experienced by tobacco workers in North Carolina. Hundreds of thousands of farmworkers and farmers in the United States and Canada, as well as agricultural workers around the world, share this burden of nicotine exposure and dose. These results support the need to change work practices and regulations to protect workers. They also document the need to delineate the health effects of long-term exposure to high transdermal nicotine doses. PMID- 26377520 TI - Point-of-Sale Cigarette Marketing, Urge to Buy Cigarettes, and Impulse Purchases of Cigarettes: Results From a Population-Based Survey. AB - AIMS: Our aim was to examine the association of exposure to point-of-sale (POS) cigarette marketing for one's regular brand, as well as any brand of cigarettes, with the urge to buy cigarettes and frequency of impulse purchases of cigarettes. METHODS: Nine hundred ninety-nine smokers in Omaha, Nebraska were interviewed via telephone. Cigarette marketing was measured by asking respondents questions about noticing pack displays, advertisements, and promotions such as discounts for their regular brand as well as any brand of cigarettes in their neighborhoods stores. We measured urge to buy cigarettes with the question "When you are in a store in your neighborhood that sells tobacco products, how often do you get an urge to buy cigarettes?" We measured frequency of impulse purchases of cigarettes with the question "When you are shopping in a store in your neighborhood for something other than cigarettes, how often do you decide to buy cigarettes?" We estimated ordinary least squares linear regression models to address the study aim. RESULTS: Higher levels of POS marketing for one's regular brand and any brands of cigarettes were associated with more frequent urges to buy (P < .001 and P < .001, respectively) and impulse purchases of cigarettes (P = .01 and P = .013, respectively), after adjusting for covariates. CONCLUSION: Exposure to POS marketing for one's own brand of cigarette as well as any brand is associated with urges to buy and impulse purchases of cigarettes. IMPLICATIONS: Existing studies on the association of POS cigarette marketing with urge to buy and an impulse purchase of cigarettes only focus on cigarette pack displays, not on advertisements and promotions. Also, these studies make no distinction between marketing for the smokers' regular brand and any brand of cigarettes. This study found that Exposure to POS marketing for one's own brand of cigarette as well as any brand is associated with urges to buy and impulse purchases of cigarettes. Our findings can provide part of the evidence-base needed by the Food and Drug Administration or local authorities to regulate POS marketing. PMID- 26377521 TI - Application of capillary immunoelectrophoresis revealed an age- and gender dependent regulated expression of PrPC in liver. AB - The cellular prion protein (PrPC) is a glycoprotein, anchored to the plasma membrane and abundantly expressed in the central nervous system. The expression of PrPC in the peripheral tissues is low and only little information is available on its functions in the nonneuronal tissues. The antioxidant function of PrPC during the activation of hepatic stellate cells has already been reported. Therefore, the aim of the study was to expand our knowledge on the functions of PrPC by detailed characterization of its expressional profile in the liver. In a combined strategy by using capillary immunoelectrophoresis and standard techniques, we have shown a sexually dimorphic expression of PrPC in mice and human liver tissues. Further, we showed a significant age-dependent upregulation of PrPC expression in the liver of 14- and 9-month-old mice as compared to 3 months of age. Therefore, this study may provide new insights into the gender specific role of PrPC in the liver, which may further be linked to its protective role against oxidative stress during aging. In addition, the current study also shows an application of immunoelectrophoresis with a low coefficient of variation to analyze the miniscule amount of PrPC in the mouse liver tissue. PMID- 26377522 TI - Stigmatizing Images in Obesity Health Campaign Messages and Healthy Behavioral Intentions. AB - Background Antiobesity campaigns blaming individual behaviors for obesity have sparked concern that an emphasis on individual behavior may lead to stigmatization of overweight or obese people. Past studies have shown that perpetuating stigma is not effective for influencing behavior. Purpose This study examined whether stigmatizing or nonstigmatizing images and text in antiobesity advertisements led to differences in health-related behavioral intentions. Method Participants in this experiment were 161 American adults. Measures included self reported body mass index, weight satisfaction, antifat attitudes, and intention to increase healthy behaviors. Results Images in particular prompted intention to increase healthy behavior, but only among participants who were not overweight or obese. Conclusion Images and text emphasizing individual responsibility for obesity may influence behavioral intention among those who are not overweight, but they do not seem to be effective at altering behavioral intentions among overweight people, the target audience for many antiobesity messages. Images in antiobesity messages intended to alter behavior are influential and should be selected carefully. PMID- 26377523 TI - Evaluating the ParticipACTION "Think Again" Campaign. AB - Introduction ParticipACTION's 2011 "Think Again" campaign aimed to draw parents', and specifically mothers', attention to the amount of physical activity (PA) their children do relative to the national guidelines (physical activity guidelines [PAG]). Purpose To evaluate ParticipACTION's "Think Again" campaign in the context of the hierarchy of effects model. Methods Data were drawn from "Think Again" campaign evaluations conducted among two cohorts of parents with children ages 5 to 11 years (3 months postcampaign launch [T1], n = 702; 15 months postlaunch [T2], n = 670). Results At T2, campaign awareness was weakly associated with parents agreeing that their children were not active enough (p = .01, d = .18). Parents who were aware of the campaign showed greater knowledge of PAG (ps < .01, phis > .14), had higher outcome expectations about their children engaging in PA (p < .01, d = .16), had stronger intentions to help their child meet the guidelines (p < .01, d = .18), and engaged in more parental support behaviors (p < .001, d = .31) as compared with parents who were not aware. At T1, parents aware of the campaign had greater perceived behavioral control (PBC) to influence their child's PA participation (p < .01, d = .22), whereas parents not aware of the campaign had greater PBC to find practical ways to help their child be active (p < .01, d = .26). Parental awareness of the campaign was not associated with children meeting the PAG at either time point (ps > .05). Conclusions The campaign appeared marginally effective for increasing parental knowledge of PAG and for creating realistic awareness of children's PA levels. Additional intervention strategies are needed to produce larger effects and to change parental behavior. PMID- 26377524 TI - Cancer Fatalism, Literacy, and Cancer Information Seeking in the American Public. AB - Information seeking is an important behavior for cancer prevention and control, but inequalities in the communication of information about the disease persist. Conceptual models have suggested that low health literacy is a barrier to information seeking, and that fatalistic beliefs about cancer may be a mediator of this relationship. Cancer fatalism can be described as deterministic thoughts about the external causes of the disease, the inability to prevent it, and the inevitability of death at diagnosis. This study aimed to examine the associations between these constructs and sociodemographic factors, and test a mediation model using the American population-representative Health Information and National Trends Survey (HINTS 4), Cycle 3 (n = 2,657). Approximately one third (34%) of the population failed to answer 2/4 health literacy items correctly (limited health literacy). Many participants agreed with the fatalistic beliefs that it seems like everything causes cancer (66%), that one cannot do much to lower his or her chances of getting cancer (29%), and that thinking about cancer makes one automatically think about death (58%). More than half of the population had "ever" sought information about cancer (53%). In analyses adjusted for sociodemographic characteristics and family cancer history, people with limited health literacy were less likely to have ever sought cancer information (odds ratio [OR] = 0.63; 0.42-0.95) and more frequently endorsed the belief that "there's not much you can do . . ." (OR = 1.61; 1.05-2.47). This fatalistic belief partially explained the relationship between health literacy and information seeking in the mediation model (14% mediation). Interventions are needed to address low health literacy and cancer fatalism to increase public interest in cancer-related information. PMID- 26377525 TI - Baseline Evaluation of a Participatory Mobile Health Intervention for Dengue Prevention in Sri Lanka. AB - Challenges posed by infectious disease outbreaks have led to a range of participatory mobile phone-based innovations that use the power of crowdsourcing for disease surveillance. However, the dynamics of participatory behavior by crowds in such interventions have yet to be examined. This article reports results from a baseline evaluation of one such intervention called Mo-Buzz, a mobile-based crowdsource-driven socially mediated system developed to address gaps in dengue surveillance and education in Colombo, Sri Lanka. We conducted a 30-minute cross-sectional field survey (N = 404) among potential users of Mo-Buzz in Colombo. We examined individual, institutional, and cultural factors that influence their potential intention-to-use Mo-Buzz and assessed if these factors varied by demographic factors. Descriptive analysis revealed high perceived ease of-use (PEOU; M = 3.81, SD = 0.44), perceived usefulness (PU; M = 4.01, SD = 0.48), and intention-to-use (PI; M = 3.91, SD = 0.46) among participants. Analysis of variance suggested participants in the 31 to 40 years age group reported highest PEOU, whereas the oldest group reported high perceived institutional efficacy (M = 3.59, SD = 0.64) and collectivistic tendencies. Significant differences (at the p < .05 level) were also found by education and income. Regression analysis demonstrated that PU, behavioral control, institutional efficacy, and collectivism were significant predictors of PI. We concluded that despite high overall PI, future adoption and use of Mo-Buzz will be shaped by a complex mix of factors at different levels of the public health ecology. Implications of study findings from theoretical and practical perspectives related to the future adoption of mobile-based participatory systems in public health are discussed and ideas for a future research agenda presented. PMID- 26377526 TI - Exploring the Link Between Alcohol and Marijuana Use and Teen Dating Violence Victimization Among High School Students: The Influence of School Context. AB - BACKGROUND: Adolescence is a developmental period when dating behavior is first initiated and when the risk of abuse by or against a dating partner begins to emerge. It is also one in which experimentation with alcohol and illicit substances typically begins. The current study examined the association between recent alcohol use and recent marijuana use and the experience of physical and verbal teen dating violence (TDV) victimization while considering the potential influence of school contextual variables. METHOD: Data came from 27,758 high school students attending 58 Maryland public high schools. Hierarchical linear modeling was used to identify student- and school-level predictors associated with TDV. RESULTS: Results indicated that approximately 11% of students reported experiencing physical TDV and 11% of students reported experiencing verbal TDV over the past year. In addition, 33% of students reported recent alcohol use and 21% reported recent marijuana use. Hierarchical linear modeling results revealed that students who reported frequent recent alcohol or recent marijuana use were at increased odds of experiencing physical (adjusted odds ratio [AOR]alcohol = 2.80, p < .001; AORmarijuana = 2.03, p < .001) or verbal TDV (AORalcohol = 2.63, p < .001; AORmarijuana = 2.20, p < .001) victimization compared to students who reported little or no alcohol or marijuana use. School support was a protective factor for both physical TDV (AOR = 0.74, p < .001) and verbal TDV (AOR = 0.76, p < .001) victimization. CONCLUSIONS: Findings suggested that prevention efforts to address alcohol and marijuana use may have an effect on TDV victimization. Results also highlight the potential utility of enhancing student perceptions of school support as an approach for reducing TDV victimization. PMID- 26377528 TI - Treatment Quality in Breast Cancer: Numbers, Age, and Breast Reconstruction. PMID- 26377529 TI - The Treatment of Primary Breast Cancer in Older Women With Adjuvant Therapy: A Retrospective Analysis of Data From Over 3000 Patients From the PATH Biobank, With Two-Year Follow-up. AB - BACKGROUND: Breast cancer is the most common cancer in women in Germany. Mortality from breast cancer has declined over the past 15 years, but less so in women aged 70 or older than in younger women. The discrepancy might be explained by age-related differences in treatment. METHODS: Data from the Patients' Tumor Bank of Hope (PATH) database of women who underwent adjuvant treatment for the treatment of an invasive primary tumor without distant metastases (year of diagnosis, 2006-2011) were retrospectively analyzed. The clinical and tumor biological findings and treatment data over two years of follow-up were compared across three age groups (under age 50, ages 50 to 69, and ages 70 and up). Chi square tests were carried out to reveal significant differences, and post-hoc multiple comparisons were performed with and without Bonferroni correction. Treatment data were adjusted for staging and grading and tested for age dependence with logistic regression. RESULTS: Follow-up data were available for 3257 (65% ) of 4981 women, of whom 61% were in the middle age group and 22% in the oldest. Compared to women aged 50 to 69, those aged 70 and up less commonly received breast-conserving treatment (68.8% vs. 86.4% ), chemotherapy (27.5% vs. 44.1% ), radiotherapy (81.8% vs. 92.4% ), and trastuzumab (52.9% vs. 79.3% ; p<0.001 for all differences). All differences remained significant after stastistical adjustment. CONCLUSION: The cause of these age-related differences is unclear. It cannot be determined from these data whether concomitant disease, the older patients' individual decisions, or other factors were responsible for their not receiving treatment as often as the younger patients did. PMID- 26377530 TI - Case Numbers and Process Quality in Breast Surgery in Germany: A Retrospective Analysis of Over 150,000 Patients From 2013 to 2014. AB - BACKGROUND: Numerous studies from around the world have shown a positive association between case numbers and the quality of medical care. The evidence to date suggests that conformity to guidelines for the treatment of patients with breast cancer is better in German hospitals that have higher case numbers. METHODS: We used data obtained by an external program for quality assurance in inpatient care (externe stationare Qualitatssicherung, esQS) for the years 2013 and 2014 to investigate seven process indicators in the area of breast surgery, including histologic confirmation of the diagnosis before definitive treatment, axillary dissection as recommended by the guidelines, and an appropriate temporal interval between diagnosis and operation. Case numbers were categorized with the aid of various threshold values. Moreover, subgroup analyses were carried out for patients under age 65, patients in good general health, patients without lymph node involvement, and patients with a tumor size pT0 or pT1 or an overall tumor size less than 5 cm. RESULTS: Data on 153,475 patients from 939 hospitals were analyzed. Six of seven indicators had values that were better overall, to a statistically significant extent, in hospitals with higher case numbers. Although this relationship was not consistently seen, the worst results were generally found in the category with the lowest case numbers. Similar though less striking results were obtained in the subgroup analyses. An exception to the general finding was that, in hospitals with higher case numbers, the interval between diagnosis and operation was more often longer than three weeks. CONCLUSION: Guideline adherence is higher in hospitals that treat more cases. The present study does not address the question whether this, in turn, affects morbidity or mortality. To improve process quality in peripheral hospitals, the quality assurance program should be continued. PMID- 26377532 TI - Marginal Effect and Little Clinical Relevance. PMID- 26377531 TI - Breast Reconstruction Following Cancer Treatment. AB - BACKGROUND: About 8000 breast reconstructions after mastectomy are per - formed in Germany each year. It has become more difficult to advise patients because of the wide variety of heterologous and autologous techniques that are now available and because of changes in the recommendations about radiotherapy. METHODS: This article is based on a review of pertinent articles (2005-2014) that were retrieved by a selective search employing the search terms "mastectomy" and "breast reconstruction." RESULTS: The goal of reconstruction is to achieve an oncologically safe and aestically satisfactory result for the patient over the long term. Heterologous, i.e., implant-based, breast reconstruction (IBR) and autologous breast reconstruction (ABR) are complementary techniques. Immediate reconstruction preserves the skin of the breast and its natural form and prevents the psychological trauma associated with mastectomy. If post-mastectomy radiotherapy (PMRT) is not indicated, implant-based reconstruction with or without a net/acellular dermal matrix (ADM) is a common option. Complications such as seroma formation, infection, and explantation are significantly more common when an ADM is used (15.3% vs. 5.4% ). If PMRT is performed, then the complication rate of implant-based breast reconstruction is 1 to 48% ; in particular, Baker grade III/IV capsular fibrosis occurs in 7 to 22% of patients, and the prosthesis must be explanted in 9 to 41% . Primary or, preferably, secondary autologous reconstruction is an alternative. The results of ABR are more stable over the long term, but the operation is markedly more complex. Autologous breast reconstruction after PMRT does not increase the risk of serious complications (20.5% vs. 17.9% without radiotherapy). CONCLUSION: No randomized controlled trials have yet been conducted to compare the reconstructive techniques with each other. If radiotherapy will not be performed, immediate reconstruction with an implant is recommended. On the other hand, if post mastectomy radiotherapy is indicated, then secondary autologous breast reconstruction is the procedure of choice. Future studies should address patients' quality of life and the long-term aesthetic results after breast reconstruction. PMID- 26377533 TI - Polysomnographic Screening Helpful. PMID- 26377535 TI - Severe Collateral Damage. PMID- 26377534 TI - In Reply. PMID- 26377536 TI - Additional Information to Increase Accuracy. PMID- 26377537 TI - The Use of Antidepressants in Patients With Benzodiazepine Dependence. PMID- 26377538 TI - In Reply. PMID- 26377539 TI - Videodermatoscopy evaluation of the distinct vascular pattern of psoriasis improves diagnostic capability for inverse psoriasis. PMID- 26377540 TI - Erythema ab igne induced by laptop computer: an emerging disease among adolescents? AB - Erythema ab igne (EAI) was a very common disease in the past, when it occurred mainly among people who worked with fire, or in people who had used heat sources in contact with the skin for warming purposes for long time. In the last decades, with the introduction of central heating in the buildings, EAI incidence was remarkably decreased in Western Countries, and it was found almost exclusively among elderly, and in people affected by defects in thermoregulation or alteration of periphery circulation. Recently, a new slight increase of EAI prevalence has been observed, although with some new features. Here, we describe three cases of adolescents who presented with brownish, reticulated patch on the anterior surface of their thighs. An accurate medical questioning revealed that the patients used to place the lower surface of laptop computer on the extensor side of their thighs in a cross-legged position for many hours (about 6-8 hours) every days. In particular, the patients supported the laptop computer always on the same leg. Laptop computer-induced EAI was diagnosed. Only a few cases of laptop computer-induced EAI have been reported in the literature. Although EAI is poorly symptomatic and it generally evolve to complete remission after a early discontinuance of heat source exposure, chronic lesions of EAI have been regarded as precancerous lesions. Therefore, it is important to implement diagnosis and prevention measures of this disease. Dermatologists should consider new causal agents for old diseases. PMID- 26377542 TI - Applications of luminous bacteria enzymes in toxicology. AB - This review describes the principle and applications of bioluminescent enzymatic toxicity bioassays. This type of assays uses bacterial coupled enzyme systems: NADH:FMN-oxidoreductase and luciferase to replace living organisms in developing cost-competitive biosensors for environmental, medical and industrial applications. These biosensors instantly signal chemical and biological hazards and allow for detecting a great amount of toxic compounds with advantages associated with fast results, high sensitivity, simplicity, low cost and safety of the procedure. PMID- 26377543 TI - Simultaneous genotyping of four single nucleotide polymorphisms associated with risk factors of hemostasis disorders. AB - Multiplex simultaneous genotyping technique was developed for four polymorphisms in genes coding for blood coagulation factors and homocysteine metabolism which are considered as thrombophilia related mutations: FV Leiden, FII G20210A, MTHFR C677T, and FVII G10976A. It is based on primer extension reaction with the following bioluminescent solid-phase microassay. At that, two dierent in bioluminescence obelin mutants were applied to simultaneous detection of two gene allelic variants. The assay is carried out in microtiter plate format and provides fast and reliable genotyping of four single nucleotide polymorphisms in four different genes within 2.5 hours. A large number of clinical samples were analyzed and the obtained results were found to be in complete correlation with those obtained by using conventional RT-PCR techniques. PMID- 26377541 TI - Current approaches in identification and isolation of human renal cell carcinoma cancer stem cells. AB - In recent years, cancer stem cells (CSCs)/tumor initiating cells (TICs) have been identified inside different tumors. However, currently used anti-cancer therapies are mostly directed against somatic tumor cells without targeting CSCs/TICs. CSCs/TICs also gain resistance to chemotherapies/radiotherapies. For the development of efficient treatment strategies, choosing the best method for isolation and characterization of CSCs/TICs is still debated among the scientific community. In this review, we summarize recent data concerning isolation techniques for CSCs using magnetic cell sorting and flow cytometry. The review focuses on the strategies for sample preparation during flow cytometric analysis, elaborating biomarkers such as CXCR4, CD105, and CD133. In addition, functional properties characteristic of CSCs/TICs using side population selection through Hoechst 33342 dye, aldehyde dehydrogenase 1, dye-cycle violet, and rhodamine 123 are also discussed. We also include a special focus on enriching CSCs/TICs using three-dimensional cell culture models such as agarose-agarose microbeads and sphere formation. PMID- 26377544 TI - Creation of artificial luciferases to expand their analytical potential. AB - Bioluminescent proteins have been intensively used as high sensitive reporters in all kinds of binding assays (immuno-, nucleic acid hybridization assays, etc.) and in bioimaging. But natural luciferases do not always meet the requirements set for them as the assay reporters: thermostabitity, definite bioluminescence spectral and kinetics characteristics, stability to chemical modifications, etc. Luciferases with different appropriate characteristics as well as various luciferin derivatives were obtained using mutagenesis and chemical synthesis. Thanks to rigorous efforts of many researchers bioluminescencebased analytical techniques offer a great potential for solving analytical tasks in the field of biotechnology, biomedicine, pharmacology, etc. PMID- 26377545 TI - Simultaneous multicolor luciferase reporter assays for monitoring of multiple genes expressions. AB - Multicolor luciferase reporter assays are powerful tools for simultaneously monitoring the expression of several genes. Dual-color luciferase reporter assays were established in 2004 and have been used in broad range of application from basic researches to applications in clinical research, e.g., drug screening and alternative toxicological tests. The advantage of this method is that it can be used to simultaneously monitor sequential and complex changes in the expression of multiple genes from the single-cell level to the tissue level. In this review, I focus on the simultaneous analysis of multiple genes using multicolor beetle luciferases. PMID- 26377546 TI - Bioanalytical systems based on bioluminescence resonance energy transfer using firefly luciferase. AB - Bioanalytical systems based on the Bioluminescence Resonance Energy Transfer (BRET) are widely used in fundamental biochemical studies, as well as for screening and analysis of biologically active compounds. The Renilla luciferase is the most often used energy donor in this system despite the fact that it has low bioluminescence quantum yield and demonstrates not so stable luminescence in time as the firefly luciferase. Moreover, the bioluminescence lambdamax is observed in the green region of the spectrum, which complicates signal recording in tissues during in vivo experiments. The firefly luciferases do not have such drawbacks and show great promise for applications in BRET systems. Different versions of BRET systems based on firefly luciferases and the methods for increasing their efficiency are considered in this review; examples of the use of BRET systems based on the firefly luciferases for highly sensitive determination of proteases and for homogeneous immunoassays are presented. PMID- 26377547 TI - Intracranial complications associated with spinal surgery. AB - PURPOSE: Though rare, intracranial complications have been reported as a result from spinal surgery. Most if not all of these are a result of intracranial hypotension from durotomy and cerebrospinal fluid (CSF) leak. We aimed to characterize these complications across a large postoperative population at our institution. METHODS: We conducted a retrospective review of all patients who underwent spinal surgery at our institution by four neurosurgeons from July 2008 to August 2013. RESULTS: Our review yielded 1113 consecutive patients who underwent spinal surgery for a total of 1396 procedures. Intracranial imaging using either computed tomography or magnetic resonance imaging was obtained on 59 (4.2%) patients after a procedure due to neurologic change. Six patients (0.4%) were found to have intracranial findings of subdural hygroma (4 patients), remote cerebellar hemorrhage (1 patient), or subdural hematoma (1 patient). CONCLUSION: Intracranial complications from spinal surgery are a rare event. We demonstrate an incidence of 0.4% of total intracranial pathology after spinal surgery. A strong clinical suspicion must be maintained after durotomy or CSF leak due to these infrequent but potentially life-threatening complications. PMID- 26377548 TI - Musical ability is associated with enhanced auditory and visual cognitive processing. AB - BACKGROUND: Musical ability has always been linked to enhanced cognitive and intellectual skills. We were interested in the relation between musical ability and short-time cognitive processing as measured by event-related potentials, in particular in visual processing, since previous studies have already suggested such a link for acoustic cognitive processing. We measured auditory and visual event-related potentials as elicited by an oddball paradigm in 20 healthy subjects (10 musicians and 10 non-musicians; 10 female; mean age 24 +/- 2 years). In addition, the Seashore test and a test developed by the authors to detect relevant amusia, the latter one with a high ceiling effect, were also applied. RESULTS: The most important finding was that there is a significant linear correlation between musical ability as measured by these tests and the P3 latencies of both the auditory and visual event-related potentials. Furthermore, musicians showed shorter latencies of the event-related potentials than non musicians. CONCLUSIONS: We conclude that musical ability as measured by neuropsychological tests is associated with improved short-time cognitive processing both in the auditory and, surprisingly, also in the visual domain. PMID- 26377549 TI - Premature baby with extreme hyponatraemia (95 mmol per litre): a case report. AB - BACKGROUND: Whilst mild neonatal hyponatraemia is common and relatively harmless, extreme hyponatraemia of 95 mmol per litre has never been reported in a premature baby and such a level could be associated with immediate as well as long-lasting detrimental effects on health. CASE PRESENTATION: Twenty-four days old baby boy born at 28 weeks gestation (triplet one) unexpectedly became moribund with hypovolaemic shock and was found to have blood sodium of 95 mmol per litre. Diagnostic work up revealed a combination of a urinary tract infection, inadvertently low sodium provision with donor breast milk, and weak renin angiotensin-aldosterone response. Commencement of treatment with intravenous fluids and extra sodium led to unanticipated diuresis and faster than expected increase of sodium level. Ultimately, treatment resulted in clinical recovery and normalisation of sodium level, which subsequently remained normal with no additional sodium supplementation. Follow up revealed mild spastic diplegia. CONCLUSION: Continuous monitoring and daily medical reviews may not be sensitive enough to recognise development of extreme hyponatraemia. Blood sodium levels should be monitored closely and any abnormalities promptly addressed. Treatment of hypovolaemic hyponatraemia should be centred on fluid resuscitation, anticipation of "paradoxical" diuresis, and blood sodium correction rate of 8 to 10 mmol per litre per day. PMID- 26377551 TI - Medicinal Cannabis: A Survey Among Health Care Providers in Washington State AB - INTRODUCTION: Washington State allows marijuana use for medical (since 1998) and recreational (since 2012) purposes. The benefits of medicinal cannabis (MC) can be maximized if clinicians educate patients about dosing, routes of administration, side effects, and plant composition. However, little is known about clinicians' knowledge and practices in Washington State. METHODS: An anonymous online survey assessed providers' MC knowledge, beliefs, clinical practices, and training needs. The survey was disseminated through health care providers' professional organizations in Washington State. Descriptive analysis compared providers who had and had not authorized MC for patients. Survey results informed the approach and content of an online training on best clinical practices of MC. RESULTS: Four hundred ninety-four health care providers responded to the survey. Approximately two-third were women, aged 30 to 60 years, and working in family or internal medicine. More than half of the respondents were legally allowed to write MC authorizations per Washington State law, and 27% of those had issued written MC authorizations. Overall, respondents reported low knowledge and comfort level related to recommending MC. Respondents rated MC knowledge as important and supported inclusion of MC training in medical/health provider curriculum. Most Washington State providers have not received education on scientific basis of MC or training on best clinical practices of MC. Clinicians who had issued MC authorizations were more likely to have received MC training than those who had not issued MC authorization. DISCUSSION: The potential of MCs to benefit some patients is hindered by the lack of comfort of clinicians to recommend it. Training opportunities are badly needed to address these issues. PMID- 26377552 TI - A Formal Palliative Care Service Improves the Quality of Care in Patients with Stage IV Cancer and Bowel Obstruction. AB - BACKGROUND: Patients with stage IV cancer and bowel obstruction present a complicated management problem. The aim of this study was to evaluate the role of the palliative care service (PC) in the management of this complex disease process. METHODS: A retrospective analysis was conducted of all patients admitted to Roswell Park Cancer Institute with stage IV cancer and bowel obstruction from 2009 to 2012 after the institution of a formal PC. This cohort was matched to similar patients from 2005 to 2008 (no palliative care service or NPC). Patient characteristics and outcomes included baseline demographics, comorbid conditions, do-not-resuscitate (DNR) status, laboratory parameters, medical and surgical management, length of stay, symptom relief, and disposition status. RESULTS: A total of 19 patients were identified in the PC group. Based on the PC group baseline characteristics, 19 patients were identified for the NPC group using matched values. Regarding outcomes, there were significant differences in the medication regimens (narcotics, octreotide, and Decadron) between the 2 groups. In the PC group, 14 of 19 patients showed improvement compared to 9 of 19 in the NPC group. Nearly 60% of patients in the PC group had a formal DNR order versus 10.5% in NPC ( P = .002). A significantly higher percentage of patients were discharged to hospice in the PC group (47.4% vs 0.0%, P = .006). CONCLUSION: Palliative care consultation improves the quality of care for patients with stage IV cancer and bowel obstruction, with particular benefits in symptom management, end-of-life discussion, and disposition to hospice. PMID- 26377550 TI - A pilot randomized trial of conventional versus advanced pelvic floor exercises to treat urinary incontinence after radical prostatectomy: a study protocol. AB - BACKGROUND: Radical prostatectomy is the most common and effective treatment for localized prostate cancer. Unfortunately, radical prostatectomy is associated with urinary incontinence and has a significant negative impact on quality of life. Pelvic floor exercises are the most common non-invasive management strategy for urinary incontinence following radical prostatectomy; however, studies provide inconsistent findings regarding their efficacy. One potential reason for sub-optimal efficacy of these interventions is the under-utilization of regional muscles that normally co-activate with the pelvic floor, such as the transverse abdominis, rectus abdominis, and the diaphragm. Two novel approaches to improve urinary continence recovery are 'Pfilates' and 'Hypopressives' that combine traditional pelvic floor exercises with the activation of additional supportive muscles. Our study will compare an advanced pelvic floor exercise training program that includes Pfilates and Hypopressives, to a conventional pelvic floor exercises regimen for the treatment of post-radical prostatectomy urinary incontinence. METHODS/DESIGN: This is a pilot, randomized controlled trial of advanced pelvic floor muscle training versus conventional pelvic floor exercises for men with localized prostate cancer undergoing radical prostatectomy. Eighty eight men who will be undergoing radical prostatectomy at hospitals in Toronto, Canada will be recruited. Eligible participants must not have undergone androgen deprivation therapy and/or radiation therapy. Participants will be randomized 1:1 to receive 26 weeks of the advanced or conventional pelvic floor exercise programs. Each program will be progressive and have comparable exercise volume. The primary outcomes are related to feasibility for a large, adequately powered randomized controlled trial to determine efficacy for the treatment of urinary incontinence. Feasibility will be assessed via recruitment success, participant retention, outcome capture, intervention adherence, and prevalence of adverse events. Secondary outcomes of intervention efficacy include measures of pelvic floor strength, urinary incontinence, erectile function, and quality of life. Secondary outcome measures will be collected prior to surgery (baseline), and at 2, 6, 12, 26-weeks post-operatively. DISCUSSION: Pfilates and Hypopressives are novel approaches to optimizing urinary function after radical prostatectomy. This trial will provide the foundation of data for future, large-scale trials to definitively describe the effect of these advanced pelvic floor exercise modalities compared to conventional pelvic floor exercise regimes for men with prostate cancer undergoing radical prostatectomy TRIAL REGISTRATION: Clinicalstrials.gov Identifier: NCT02233608. PMID- 26377553 TI - Using activity triggered e-diaries to reveal the associations between physical activity and affective states in older adult's daily living. AB - BACKGROUND: Evidence suggests that older adults show positive affects after participating in exercise bouts. However, it is less clear, if and how physical activities in daily living enhance affective states, too. This is dissatisfying, as most of older adults' physical activities are part of their daily living. To answer these questions we used activity-triggered e-diaries to investigate the within-subject effects of physical activity on three dimensions of affective states (valence, energetic arousal, calmness) during everyday life. METHODS: Older adults (N = 74) between 50 and 70 years took part in the study during three consecutive days. Physical activity in daily living was objectively assessed using accelerometers. Affects were measured 10 min after a study participant surpassed a predefined threshold for activity or inactivity. The participants were prompted by an acoustic signal to assess their momentary affective states on an e-diary. Data were analyzed with hierarchical multilevel analyses. RESULTS: Whenever older individuals were more physically active, they felt more energized (energetic arousal) and agitated (calmness). However, they did not feel better (valence). Interestingly, body mass index (BMI) and valence were associated in a significant cross-level interaction. BMI acts as a moderating variable in the way that lower BMI scores were associated with higher levels of valence scores after being physically active. CONCLUSIONS: The innovative ambulatory assessment used here affords an interesting insight to the affective effects of daily activity of older adults. These effects are no simple and no linear ones, i.e. physical activity is not associated with positive affects per se as shown several times in experimental studies with single activity bouts. Rather there is a differentiating association seen as an enhanced feeling of energy and agitation, which is not accompanied by a better feeling. Socio-emotional selectivity theory may support the finding that older individuals are emotionally more stable during their day-to-day life, which might explain the non-significant effect on the affect dimension valence. PMID- 26377555 TI - [Ligament reconstruction for trapeziometacarpal joint instability]. AB - OBJECTIVE: Restoring stability and preventing subluxation/dislocation of the trapeziometacarpal (first carpometacarpal = CMC-I) joint while preserving mobility. INDICATIONS: Posttraumatic, acquired or congenital instability of the CMC-I joint. CONTRAINDICATIONS: Existence of osteoarthritis of the CMC-I joint. Neurogenic or muscular origin dysfunction of thenar muscles and other contractures the CMC-I area. Infections. SURGICAL TECHNIQUE: Radiopalmar approach to the CMC-I joint, reduction, and transosseous ligament reconstruction with a distally pedicled tendon strip from the abductor pollicis longus muscle. POSTOPERATIVE MANAGEMENT: Splint immobilization for 5 weeks. RESULTS: This procedure generally results in good or very good outcomes. Of 24 patients, only one patient experienced rupture of the ligament reconstruction. Ligament reconstruction for the carpometacarpal joint of the thumb relieves pain and restores stability while preserving functional range of motion in patients with chronic instability. PMID- 26377554 TI - Mast cells in meningiomas and brain inflammation. AB - BACKGROUND: Research focus in neuro-oncology has shifted in the last decades towards the exploration of tumor infiltration by a variety of immune cells and their products. T cells, macrophages, B cells, and mast cells (MCs) have been identified. METHODS: A systematic review of the literature was conducted by searching PubMed, EMBASE, Google Scholar, and Turning Research into Practice (TRIP) for the presence of MCs in meningiomas using the terms meningioma, inflammation and mast cells. RESULTS: MCs have been detected in various tumors of the central nervous system (CNS), such as gliomas, including glioblastoma multiforme, hemangioblastomas, and meningiomas as well as metastatic brain tumors. MCs were present in as many as 90 % of all high-grade meningiomas mainly found in the perivascular areas of the tumor. A correlation between peritumoral edema and MCs was found. INTERPRETATION: Accumulation of MCs in meningiomas could contribute to the aggressiveness of tumors and to brain inflammation that may be involved in the pathogenesis of additional disorders. PMID- 26377556 TI - Increasing blood flow to exercising muscle attenuates systemic cardiovascular responses during dynamic exercise in humans. AB - Reducing blood flow to working muscles during dynamic exercise causes metabolites to accumulate within the active muscles and evokes systemic pressor responses. Whether a similar cardiovascular response is elicited with normal blood flow to exercising muscles during dynamic exercise remains unknown, however. To address that issue, we tested whether cardiovascular responses are affected by increases in blood flow to active muscles. Thirteen healthy subjects performed dynamic plantarflexion exercise for 12 min at 20%, 40%, and 60% of peak workload (EX20, EX40, and EX60) with their lower thigh enclosed in a negative pressure box. Under control conditions, the box pressure was the same as the ambient air pressure. Under negative pressure conditions, beginning 3 min after the start of the exercise, the box pressure was decreased by 20, 45, and then 70 mmHg in stepwise fashion with 3-min step durations. During EX20, the negative pressure had no effect on blood flow or the cardiovascular responses measured. However, application of negative pressure increased blood flow to the exercising leg during EX40 and EX60. This increase in blood flow had no significant effect on systemic cardiovascular responses during EX40, but it markedly attenuated the pressor responses otherwise seen during EX60. These results demonstrate that during mild exercise, normal blood flow to exercising muscle is not a factor eliciting cardiovascular responses, whereas it elicits an important pressor effect during moderate exercise. This suggests blood flow to exercising muscle is a major determinant of cardiovascular responses during dynamic exercise at higher than moderate intensity. PMID- 26377558 TI - Prolactin 177, prolactin 188, and extracellular osmolality independently regulate the gene expression of ion transport effectors in gill of Mozambique tilapia. AB - This study characterized the local effects of extracellular osmolality and prolactin (PRL) on branchial ionoregulatory function of a euryhaline teleost, Mozambique tilapia (Oreochromis mossambicus). First, gill filaments were dissected from freshwater (FW)-acclimated tilapia and incubated in four different osmolalities, 280, 330, 380, and 450 mosmol/kg H2O. The mRNA expression of Na(+)/K(+)-ATPase alpha1a (NKA alpha1a) and Na(+)/Cl(-) cotransporter (NCC) showed higher expression with decreasing media osmolalities, while Na(+)/K(+)/2Cl(-) cotransporter 1a (NKCC1a) and PRL receptor 2 (PRLR2) mRNA levels were upregulated by increases in media osmolality. We then incubated gill filaments in media containing ovine PRL (oPRL) and native tilapia PRLs (tPRL177 and tPRL188). oPRL and the two native tPRLs showed concentration-dependent effects on NCC, NKAalpha1a, and PRLR1 expression; Na(+)/H(+) exchanger 3 (NHE3) expression was increased by 24 h of incubation with tPRLs. Immunohistochemical observation showed that oPRL and both tPRLs maintained a high density of NCC- and NKA-immunoreactive ionocytes in cultured filaments. Furthermore, we found that tPRL177 and tPRL188 differentially induce expression of these ion transporters, according to incubation time. Together, these results provide evidence that ionocytes of Mozambique tilapia may function as osmoreceptors, as well as directly respond to PRL to modulate branchial ionoregulatory functions. PMID- 26377557 TI - Cardiac responses to hypoxia and reoxygenation in Drosophila. AB - An adequate supply of oxygen is important for the survival of all tissues, but it is especially critical for tissues with high-energy demands, such as the heart. Insufficient tissue oxygenation occurs under a variety of conditions, including high altitude, embryonic and fetal development, inflammation, and thrombotic diseases, often affecting multiple organ systems. Responses and adaptations of the heart to hypoxia are of particular relevance in human cardiovascular and pulmonary diseases, in which the effects of hypoxic exposure can range in severity from transient to long-lasting. This study uses the genetic model system Drosophila to investigate cardiac responses to acute (30 min), sustained (18 h), and chronic (3 wk) hypoxia with reoxygenation. Whereas hearts from wild-type flies recovered quickly after acute hypoxia, exposure to sustained or chronic hypoxia significantly compromised heart function upon reoxygenation. Hearts from flies with mutations in sima, the Drosophila homolog of the hypoxia-inducible factor alpha subunit (HIF-alpha), exhibited exaggerated reductions in cardiac output in response to hypoxia. Heart function in hypoxia-selected flies, selected over many generations for survival in a low-oxygen environment, revealed reduced cardiac output in terms of decreased heart rate and fractional shortening compared with their normoxia controls. Hypoxia-selected flies also had smaller hearts, myofibrillar disorganization, and increased extracellular collagen deposition, consistent with the observed reductions in contractility. This study indicates that longer-duration hypoxic insults exert deleterious effects on heart function that are mediated, in part, by sima and advances Drosophila models for the genetic analysis of cardiac-specific responses to hypoxia and reoxygenation. PMID- 26377559 TI - The location of pacemakers in the uteri of pregnant guinea pigs and rats. AB - The pregnant uterus is a smooth muscle organ whose pattern of contraction is dictated by the propagation of electrical impulses. Such electrical activity may originate from one or more pacemakers, but the location of these sites has not yet been determined. To detect the location of the pacemaker in the gravid uterus, two approaches were used: 1) determine the site from where the contraction started using isolated uteri from the pregnant guinea pig, and videotape their contractions; and 2) record, in isolated uteri from pregnant term rats, with 240 extracellular electrodes simultaneously, and determine where the electrical bursts started. In both the contractile and electrophysiological experiments, there was not a single, specific pacemaker area. However, most contractions (guinea pig 87%) and bursts (rat 76%) started close to the mesometrial border (mean 2.7 +/- 4.0 mm SD in guinea pigs and 1.3 +/- 1.4 mm in rats). In addition, in the rat, most sites of initiations were located closer to the ovarial end of the horn (mean distance from the ovarial end 6.0 +/- 6.2 mm SD), whereas such an orientation was not seen in the guinea pig. In both guinea pig and rat uteri at term, there is not one specific pacemaker area. Rather, contractile and electrical activity may arise from any site, with the majority starting close to the mesometrial border. Furthermore, in the rat, most activities started at the ovarial end of the horn. This may suggest a slightly different pattern of contraction in both species. PMID- 26377560 TI - Muscle metaboreceptors modulate postexercise sweating, but not cutaneous blood flow, independent of baroreceptor loading status. AB - We examined whether sustained changes in baroreceptor loading status during prolonged postexercise recovery can alter the metaboreceptors' influence on heat loss. Thirteen young males performed a 1-min isometric handgrip exercise (IHG) at 60% maximal voluntary contraction followed by 2 min of forearm ischemia (to activate metaboreceptors) before and 15, 30, 45, and 60 min after a 15-min intense treadmill running exercise (>90% maximal heart rate) in the heat (35 degrees C). This was repeated on three separate days with continuous lower body positive (LBPP, +40 mmHg), negative (LBNP, -20 mmHg), or no pressure (Control) from 13- to 65-min postexercise. Sweat rate (ventilated capsule; forearm, chest, upper back) and cutaneous vascular conductance (CVC; forearm, upper back) were measured. Relative to pre-IHG levels, sweating at all sites increased during IHG and remained elevated during ischemia at baseline and similarly at 30, 45, and 60 min postexercise (site average sweat rate increase during ischemia: Control, 0.13 +/- 0.02; LBPP, 0.12 +/- 0.02; LBNP, 0.15 +/- 0.02 mg.min(-1).cm(-2); all P < 0.01), but not at 15 min (all P > 0.10). LBPP and LBNP did not modulate the pattern of sweating to IHG and ischemia (all P > 0.05). At 15-min postexercise, forearm CVC was reduced from pre-IHG levels during both IHG and ischemia under LBNP only (ischemia: 3.9 +/- 0.8% CVCmax; P < 0.02). Therefore, we show metaboreceptors increase postexercise sweating in the middle to late stages of recovery (30-60 min), independent of baroreceptor loading status and similarly between skin sites. In contrast, metaboreflex modulation of forearm but not upper back CVC occurs only in the early stages of recovery (15 min) and is dependent upon baroreceptor unloading. PMID- 26377561 TI - Differences in the dynamic baroreflex characteristics of unmyelinated and myelinated central pathways are less evident in spontaneously hypertensive rats. AB - The aim of the study was to identify the contribution of myelinated (A-fiber) and unmyelinated (C-fiber) baroreceptor central pathways to the baroreflex control of sympathetic nerve activity (SNA) and arterial pressure (AP) in anesthetized Wistar-Kyoto (WKY; n = 8) and spontaneously hypertensive rats (SHR; n = 8). The left aortic depressor nerve (ADN) was electrically stimulated with two types of binary white noise signals designed to preferentially activate A-fibers (A-BRx protocol) or C-fibers (C-BRx protocol). In WKY, the central arc transfer function from ADN stimulation to SNA estimated by A-BRx showed strong derivative characteristics with the slope of dynamic gain between 0.1 and 1 Hz (Gslope) of 14.63 +/- 0.89 dB/decade. In contrast, the central arc transfer function estimated by C-BRx exhibited nonderivative characteristics with Gslope of 0.64 +/ 1.13 dB/decade. This indicates that A-fibers are important for rapid baroreflex regulation, whereas C-fibers are likely important for more sustained regulation of SNA and AP. In SHR, the central arc transfer function estimated by A-BRx showed higher Gslope (18.46 +/- 0.75 dB/decade, P < 0.01) and that estimated by C BRx showed higher Gslope (8.62 +/- 0.64 dB/decade, P < 0.001) with significantly lower dynamic gain at 0.01 Hz (6.29 +/- 0.48 vs. 2.80 +/- 0.36%/Hz, P < 0.001) compared with WKY. In conclusion, the dynamic characteristics of the A-fiber central pathway are enhanced in the high-modulation frequency range (0.1-1 Hz) and those of the C-fiber central pathway are attenuated in the low-modulation frequency range (0.01-0.1 Hz) in SHR. PMID- 26377562 TI - Accelerated age-related decline in renal and vascular function in female rats following early-life growth restriction. AB - Many studies report sexual dimorphism in the fetal programming of adult disease. We hypothesized that there would be differences in the age-related decline in renal function between male and female intrauterine growth-restricted rats. Early life growth restriction was induced in rat offspring by administering a low protein diet (LPD; 8.7% casein) to dams during pregnancy and lactation. Control dams were fed a normal-protein diet (NPD; 20% casein). Mean arterial pressure (MAP) and renal structure and function were assessed in 32- and 100-wk-old offspring. Mesenteric artery function was examined at 100 wk using myography. At 3 days of age, body weight was ~24% lower (P < 0.0001) in LPD offspring; this difference was still apparent at 32 wk but not at 100 wk of age. MAP was not different between the male NPD and LPD groups at either age. However, MAP was greater in LPD females compared with NPD females at 100 wk of age (~10 mmHg; P < 0.001). Glomerular filtration rate declined with age in the NPD male, LPD male and LPD female offspring (~45%, all P < 0.05), but not in NPD female offspring. Mesenteric arteries in the aged LPD females had reduced sensitivity to nitric oxide donors compared with their NPD counterparts, suggesting that vascular dysfunction may contribute to the increased risk of disease in aged females. In conclusion, females growth-restricted in early life were no longer protected from an age-related decline in renal and arterial function, and this was associated with increased arterial pressure without evidence of renal structural damage. PMID- 26377564 TI - Erratum to: A prospective evaluation of ultrasound as a diagnostic tool in acute microcrystalline arthritis. PMID- 26377563 TI - NF-kappaB-dependent airway inflammation triggers systemic insulin resistance. AB - Inflammatory lung diseases (e.g., pneumonia and acute respiratory distress syndrome) are associated with hyperglycemia, even in patients without a prior diagnosis of Type 2 diabetes. It is unknown whether the lung inflammation itself or the accompanying comorbidities contribute to the increased risk of hyperglycemia and insulin resistance. To investigate whether inflammatory signaling by airway epithelial cells can induce systemic insulin resistance, we used a line of doxycycline-inducible transgenic mice that express a constitutive activator of the NF-kappaB in airway epithelial cells. Airway inflammation with accompanying neutrophilic infiltration was induced with doxycycline over 5 days. Then, hyperinsulinemic-euglycemic clamps were performed in chronically catheterized, conscious mice to assess insulin action. Lung inflammation decreased the whole body glucose requirements and was associated with secondary activation of inflammation in multiple tissues. Metabolic changes occurred in the absence of hypoxemia. Lung inflammation markedly attenuated insulin-induced suppression of hepatic glucose production and moderately impaired insulin action in peripheral tissues. The hepatic Akt signaling pathway was intact, while hepatic markers of inflammation and plasma lactate were increased. As insulin signaling was intact, the inability of insulin to suppress glucose production in the liver could have been driven by the increase in lactate, which is a substrate for gluconeogenesis, or due to an inflammation-driven signal that is independent of Akt. Thus, localized airway inflammation that is observed during inflammatory lung diseases can contribute to systemic inflammation and insulin resistance. PMID- 26377565 TI - Protective efficacy of an inactivated vaccine against H9N2 avian influenza virus in ducks. AB - BACKGROUND: Wild ducks play an important role in the evolution of avian influenza viruses (AIVs). Domestic ducks in China are known to carry and spread H9N2 AIVs that are thought to have contributed internal genes for the recent outbreak of zoonotic H7N9 virus. In order to protect animal and public health, an effective vaccine is urgently needed to block and prevent the spread of H9N2 virus in ducks. We developed an inactivated H9N2 vaccine (with adjuvant Montanide ISA 70VG) based on an endemic H9N2 AIV and evaluated this vaccine in ducks. FINDINGS: The results showed that the inactivated H9N2 vaccine was able to induce a strong and fast humoral immune response in vaccinated ducks. The hemagglutination inhibition titer in the sera increased fast, and reached its peak of 12.3 log2 at 5 weeks post-vaccination in immunized birds and remained at a high level for at least 37 weeks post-vaccination. Moreover, viral shedding was completely blocked in vaccinated ducks after challenge with a homologous H9N2 AIV at both 3 and 37 weeks post-vaccination. CONCLUSIONS: The results of this study indicate that the inactivated H9N2 vaccine induces high and prolonged immune response in vaccinated ducks and are efficacious in protecting ducks from H9N2 infection. PMID- 26377566 TI - Differential expression of Mediator complex subunit MED15 in testicular germ cell tumors. AB - BACKGROUND: Testicular germ cell tumors (TGCT) are the most common cancer entities in young men with increasing incidence observed in the last decades. For therapeutic management it is important, that TGCT are divided into several histological subtypes. MED15 is part of the multiprotein Mediator complex which presents an integrative hub for transcriptional regulation and is known to be deregulated in several malignancies, such as prostate cancer and bladder cancer role, whereas the role of the Mediator complex in TGCT has not been investigated so far. Aim of the study was to investigate the implication of MED15 in TGCT development and its stratification into histological subtypes. METHODS: Immunohistochemical staining (IHC) against Mediator complex subunit MED15 was conducted on a TGCT cohort containing tumor-free testis (n = 35), intratubular germ cell neoplasia unclassified (IGCNU, n = 14), seminomas (SEM, n = 107) and non-seminomatous germ cell tumors (NSGCT, n = 42), further subdivided into embryonic carcinomas (EC, n = 30), yolk sac tumors (YST, n = 5), chorionic carcinomas (CC, n = 5) and teratomas (TER, n = 2). Quantification of MED15 protein expression was performed through IHC followed by semi-quantitative image analysis using the Definiens software. RESULTS: In tumor-free seminiferous tubules, MED15 protein expression was absent or only low expressed in spermatogonia. Interestingly, the precursor lesions IGCNU exhibited heterogeneous but partly very strong MED15 expression. SEM weakly express the Mediator complex subunit MED15, whereas NSGCT and especially EC show significantly enhanced expression compared to tumor-free testis. CONCLUSIONS: In conclusion, MED15 is differentially expressed in tumor-free testis and TGCT. While MED15 is absent or low in tumor-free testis and SEM, NSGCT highly express MED15, hinting at the diagnostic potential of this marker to distinguish between SEM and NSGCT. Further, the precursor lesion IGCNU showed increased nuclear MED15 expression in the preinvasive precursor cells, which may provide diagnostic value to distinguish between benign and pre-malignant testicular specimen, and may indicate a role for MED15 in carcinogenesis in TGCT. PMID- 26377567 TI - Metabolic Coevolution in the Bacterial Symbiosis of Whiteflies and Related Plant Sap-Feeding Insects. AB - Genomic decay is a common feature of intracellular bacteria that have entered into symbiosis with plant sap-feeding insects. This study of the whitefly Bemisia tabaci and two bacteria (Portiera aleyrodidarum and Hamiltonella defensa) cohoused in each host cell investigated whether the decay of Portiera metabolism genes is complemented by host and Hamiltonella genes, and compared the metabolic traits of the whitefly symbiosis with other sap-feeding insects (aphids, psyllids, and mealybugs). Parallel genomic and transcriptomic analysis revealed that the host genome contributes multiple metabolic reactions that complement or duplicate Portiera function, and that Hamiltonella may contribute multiple cofactors and one essential amino acid, lysine. Homologs of the Bemisia metabolism genes of insect origin have also been implicated in essential amino acid synthesis in other sap-feeding insect hosts, indicative of parallel coevolution of shared metabolic pathways across multiple symbioses. Further metabolism genes coded in the Bemisia genome are of bacterial origin, but phylogenetically distinct from Portiera, Hamiltonella and horizontally transferred genes identified in other sap-feeding insects. Overall, 75% of the metabolism genes of bacterial origin are functionally unique to one symbiosis, indicating that the evolutionary history of metabolic integration in these symbioses is strongly contingent on the pattern of horizontally acquired genes. Our analysis, further, shows that bacteria with genomic decay enable host acquisition of complex metabolic pathways by multiple independent horizontal gene transfers from exogenous bacteria. Specifically, each horizontally acquired gene can function with other genes in the pathway coded by the symbiont, while facilitating the decay of the symbiont gene coding the same reaction. PMID- 26377569 TI - Gene-environment Interactions in the Etiology of Dental Caries. AB - Dental caries is a multifactorial disease that can be conceptualized as an interaction between genetic and environmental risk factors. The aim of this study is to examine the effects of AMELX, CA6, DEFB1, and TAS2R38 gene polymorphism and gene-environment interactions on caries etiology and susceptibility in adults. Genomic DNA was extracted from the buccal mucosa, and adults aged 20 to 60 y were placed into 1 of 2 groups: low caries risk (DMFT <= 5; n = 77) and high caries risk (DMFT >= 14; n = 77). The frequency of AMELX (+522), CA6 (T55M), DEFB1 (G 20A), and TAS2R38 (A49P) single-nucleotide polymorphisms was genotyped with the polymerase chain reaction-restriction fragment length polymorphism method. Environmental risk factors examined in the study included plaque amount, toothbrushing frequency, dietary intake between meals, saliva secretion rate, saliva buffer capacity, mutans streptococci counts, and lactobacilli counts. There was no difference between the caries risk groups in relation to AMELX (+522) polymorphism (chi(2) test, P > 0.05). The distribution of CA6 genotype and allele frequencies in the low caries risk group did not differ from the high caries risk group (chi(2) test, P > 0.05). Polymorphism of DEFB1 (G-20A) was positively associated, and TAS2R38 (A49P) negatively associated, with caries risk (chi(2) test, P = 0.000). There were significant differences between caries susceptibility and each environmental risk factor, except for the saliva secretion rate (Mann-Whitney U test, P = 0.000). Based on stepwise multiple linear regression analyses, dental plaque amount, lactobacilli count, age, and saliva buffer capacity, as well as DEFB1 (G-20A), TAS2R38 (A49P), and CA6 (T55M) gene polymorphism, explained a total of 87.8% of the variations in DMFT scores. It can be concluded that variation in CA6 (T55M), DEFB1 (G-20A), and TAS2R38 (A49P) may be associated with caries experience in Turkish adults with a high level of dental plaque, lactobacilli count, and age and when saliva buffer capacity is low. PMID- 26377568 TI - Metabolic engineering of Escherichia coli into a versatile glycosylation platform: production of bio-active quercetin glycosides. AB - BACKGROUND: Flavonoids are bio-active specialized plant metabolites which mainly occur as different glycosides. Due to the increasing market demand, various biotechnological approaches have been developed which use Escherichia coli as a microbial catalyst for the stereospecific glycosylation of flavonoids. Despite these efforts, most processes still display low production rates and titers, which render them unsuitable for large-scale applications. RESULTS: In this contribution, we expanded a previously developed in vivo glucosylation platform in E. coli W, into an efficient system for selective galactosylation and rhamnosylation. The rational of the novel metabolic engineering strategy constitutes of the introduction of an alternative sucrose metabolism in the form of a sucrose phosphorylase, which cleaves sucrose into fructose and glucose 1 phosphate as precursor for UDP-glucose. To preserve these intermediates for glycosylation purposes, metabolization reactions were knocked-out. Due to the pivotal role of UDP-glucose, overexpression of the interconverting enzymes galE and MUM4 ensured the formation of both UDP-galactose and UDP-rhamnose, respectively. By additionally supplying exogenously fed quercetin and overexpressing a flavonol galactosyltransferase (F3GT) or a rhamnosyltransferase (RhaGT), 0.94 g/L hyperoside (quercetin 3-O-galactoside) and 1.12 g/L quercitrin (quercetin 3-O-rhamnoside) could be produced, respectively. In addition, both strains showed activity towards other promising dietary flavonols like kaempferol, fisetin, morin and myricetin. CONCLUSIONS: Two E. coli W mutants were engineered that could effectively produce the bio-active flavonol glycosides hyperoside and quercitrin starting from the cheap substrates sucrose and quercetin. This novel fermentation-based glycosylation strategy will allow the economically viable production of various glycosides. PMID- 26377570 TI - Oral Microbiome Metabolism: From "Who Are They?" to "What Are They Doing?". AB - Recent advances in molecular biology have facilitated analyses of the oral microbiome ("Who are they?"); however, its functions (e.g., metabolic activities) are poorly understood ("What are they doing?"). This review aims to summarize our current understanding of the metabolism of the oral microbiome. Saccharolytic bacteria-including Streptococcus, Actinomyces, and Lactobacillus species-degrade carbohydrates into organic acids via the Embden-Meyerhof-Parnas pathway and several of its branch pathways, resulting in dental caries, while alkalization and acid neutralization via the arginine deiminase system, urease, and so on, counteract acidification. Proteolytic/amino acid-degrading bacteria, including Prevotella and Porphyromonas species, break down proteins and peptides into amino acids and degrade them further via specific pathways to produce short-chain fatty acids, ammonia, sulfur compounds, and indole/skatole, which act as virulent and modifying factors in periodontitis and oral malodor. Furthermore, it is suggested that ethanol-derived acetaldehyde can cause oral cancer, while nitrate-derived nitrite can aid caries prevention and systemic health. Microbial metabolic activity is influenced by the oral environment; however, it can also modify the oral environment, enhance the pathogenicity of bacteria, and induce microbial selection to create more pathogenic microbiome. Taking a metabolomic approach to analyzing the oral microbiome is crucial to improving our understanding of the functions of the oral microbiome. PMID- 26377571 TI - RANTES and SDF-1 Are Keys in Cell-based Therapy of TMJ Osteoarthritis. AB - The present study aimed to investigate the therapeutic effect of injections of local bone marrow mesenchymal stem cells (BMSCs) on osteoarthritis (OA) of the temporomandibular joint (TMJ) and to explore the role of stromal cell-derived factor 1 (SDF-1) and regulated on activation, normal T-cell expressed and secreted (RANTES) in this effect. Fundamentally, OA of the TMJ was induced by unilateral anterior crossbite in mice. Exogenous green fluorescent protein labeled BMSCs (GFP-BMSCs) were weekly injected into the TMJ region for 4, 8, and 12 wk. The reparative effects of exogenous GFP-BMSCs were investigated by morphological observation and micro-computed tomography. The differentiation of GFP-BMSCs in the cartilage was examined by double immunofluorescence of GFPs with type II collagen, and the expression of related factors in the condylar cartilage was quantified by real-time polymerase chain reaction. The role of RANTES and SDF 1 in the therapeutic effect of exogenous BMSCs was examined by both in vitro and in vivo studies. The OA cartilage of the TMJ displays a synchronous increase in SDF-1 and RANTES expression and a higher capability of attracting the migration of GFP-BMSCs. The implanted GFP-BMSCs differentiated into type II collagen positive cells and reversed cartilage degradation and subchondral bone loss in mice with OA of the TMJ. The migration of GFP-BMSCs towards OA cartilage and the rescuing effect of GFP-BMSC injections were impaired by the inhibitors of C-X-C chemokine receptor type 4 (CXCR4) and C-C chemokine receptor type 1 (CCR1), which are the receptors of SDF-1 and RANTES, respectively. Our data indicated that SDF 1/CXCR4 and RANTES/CCR1 signals are pivotal and function synergistically in the recruitment of GFP-BMSCs towards degraded cartilage in mice OA of the TMJ. PMID- 26377572 TI - Validation of a novel point of care testing device for sickle cell disease. AB - BACKGROUND: Sickle cell disease is one of the most common inherited blood disorders. Universal screening and early intervention have significantly helped to reduce childhood mortality in high-resource countries. However, persons living in low-resource settings are often not diagnosed until late childhood when they present with clinical symptoms. In addition, confirmation of disease in affected individuals in the urgent care setting is limited in both high- and low-resource areas, often leading to delay in treatment. All of the current diagnostic methods rely on advanced laboratory systems and are often prohibitively expensive and time-consuming in low-resource settings. To address this need, the Sickle SCANTM test has been developed to diagnose sickle cell disease and sickle cell trait at the point of care without electricity or advanced equipment. METHODS: This study was conducted to evaluate and validate the diagnostic accuracy of the Sickle SCANTM test, a novel point of care test for sickle cell disease. Thus, we describe the laboratory testing and clinical validation of the Sickle SCANTM test in individuals >1 year of age using capillary blood. The Sickle SCANTM test was created using advanced, qualitative lateral flow technology using capillary blood to identify the presence of hemoglobin A, S, and C allowing for detection of results with the naked eye. RESULTS: Laboratory testing using venous blood demonstrated 99 % sensitivity and 99 % specificity for the diagnosis of HbSS, HbAS, HbSC, HbAC, and HbAA. Seventy-one subjects underwent capillary blood sampling at the point of care for further validation. This test detected the correct A, S, and C presence with an overall diagnostic accuracy of 99 % at the bedside. CONCLUSION: The Sickle SCANTM test has the potential to significantly impact the diagnosis and treatment for sickle cell disease worldwide as well as enhance genetic counseling at the point of care. Further validation testing will be conducted in newborns in resource-poor settings in upcoming studies. PMID- 26377573 TI - Design, Synthesis, and Molecular Docking of Novel Pyrrolooxazepinediol Derivatives with Anti-Influenza Neuraminidase Activity. AB - A series of novel pyrrolo[2,1-b][1,3]oxazepine-8,9-diol derivatives 12-15 were synthesized starting from l-tartaric acid, which was transformed into anhydride which then reacted with allylamine in xylene to afford the imide 2. The target molecules 12-15 were achieved via ring-closing metathesis with the Grubbs catalyst, followed by reduction of the carbonyl group and deprotection of hydroxyl groups. Finally, catalytic hydrogenation of the double bond afforded the title compounds 12-15. Molecular docking study of the title compounds 12-15 was carried out against neuraminidase as the target enzyme, in an attempt to understand the mechanism of action of the tested compounds as potential neuraminidase inhibitors. Molecular docking of the target compounds showed that all tested compounds bind to the active site of neuraminidase, with moderate to high binding energy. Compounds 12-15 were examined for their antiviral activity against H5N1 virus (A/chicken/Egypt/1/2008). Oseltamivir phosphate was used as a control for antiviral activity. The results show that compound 12 (EC50 = 0.016 MUg/mL) exhibited potent anti-influenza (H5N1) activity, which approximately equals that of oseltamivir (EC50 = 0.012 MUg/mL). Also, it had a therapeutic index similar to that of oseltamivir phosphate (~20). The data also revealed that compounds 13, 14, and 15 had slightly lower antiviral activity and lower cytotoxicity than oseltamivir phosphate, with LD50 of 0.188, 0.162, and 0.176 MUg/mL, respectively. However, 13, 14, and 15 had lower therapeutic indices than 12. In conclusion, we were able to synthesize cheap and potent anti-H5N1 compounds. PMID- 26377574 TI - Evaluation of the optimal combinations of modulation factor and pitch for Helical TomoTherapy plans made with TomoEdge using Pareto optimal fronts. AB - BACKGROUND: Modulation factor (MF) and pitch have an impact on Helical TomoTherapy (HT) plan quality and HT users mostly use vendor-recommended settings. This study analyses the effect of these two parameters on both plan quality and treatment time for plans made with TomoEdge planning software by using the concept of Pareto optimal fronts. METHODS: More than 450 plans with different combinations of pitch [0.10-0.50] and MF [1.2-3.0] were produced. These HT plans, with a field width (FW) of 5 cm, were created for five head and neck patients and homogeneity index, conformity index, dose-near-maximum (D2), and dose-near-minimum (D98) were analysed for the planning target volumes, as well as the mean dose and D2 for most critical organs at risk. For every dose metric the median value will be plotted against treatment time. A Pareto-like method is used in the analysis which will show how pitch and MF influence both treatment time and plan quality. RESULTS: For small pitches (<=0.20), MF does not influence treatment time. The contrary is true for larger pitches (>=0.25) as lowering MF will both decrease treatment time and plan quality until maximum gantry speed is reached. At this moment, treatment time is saturated and only plan quality will further decrease. CONCLUSION: The Pareto front analysis showed optimal combinations of pitch [0.23-0.45] and MF > 2.0 for a FW of 5 cm. Outside this range, plans will become less optimal. As the vendor-recommended settings fall within this range, the use of these settings is validated. PMID- 26377575 TI - Lentzea guizhouensis sp. nov., a novel lithophilous actinobacterium isolated from limestone from the Karst area, Guizhou, China. AB - A novel filamentous actinobacterium, designated strain DHS C013(T), was isolated from limestone collected in Guizhou Province, South-west China. Morphological and chemotaxonomic characteristics of the strain support its assignment to the genus Lentzea. Phylogenetic analyses showed that strain DHS C013(T) is closely related to Lentzea jiangxiensis FXJ1.034(T) (98.7 % 16S rRNA gene similarity) and Lentzea flaviverrucosa 4.0578(T) (98.0 % 16S rRNA gene similarity), but it can be distinguished from these strains based on low levels of DNA:DNA relatedness (~44 and ~37 %, respectively). Physiological and biochemical tests also allowed phenotypic differentiation of the novel strain from these closely related species. On the basis of the evidence presented here, strain DHS C013(T) is concluded to represent a novel species of the genus Lentzea, for which the name Lentzea guizhouensis sp. nov. is proposed. The type strain is DHS C013(T) (=KCTC 29677(T) = CGMCC 4.7203(T)). PMID- 26377576 TI - Root sepsis associated with insect-dwelling Sebaldella termitidis in a lesser dwarf lemur (Cheirogaleus medius). AB - Sebaldella termitidis is a rare fastidious microorganism of the Leptotrichiaceae family. A variety of closely related species are associated with severe and even life-threatening disease in humans and animals, such as Streptobacillus moniliformis, the etiological organism of rat-bite fever as well as members of Leptotrichia spp. and Sneathia sanguinegens, which have been reported from cases of septicaemia. In contrast, since its description some 50 years ago, S. ermitidis has so far never been reported as a vertebrate pathogen, nor has it been found aside from its natural termite host. A lesser dwarf lemur was presented with unilateral facial inflammation originating from rotten maxillary teeth and septic root abscess. Surgical intervention and root extraction significantly improved the clinical cause in that a pus-filled cavity underneath the right eye could be drained, sampled and flushed. Bacteria displaying substantial characteristics of S. termitidis were cultured from the sampled pus. Morphological features observed included strictly anaerobic regular Gram-negative rods. Significant shared biochemical properties included negative reactions for cytochrome oxidase, catalase, urease, nitrate reduction and indole production. Furthermore, 16S rRNA gene sequencing revealed 99.9 % sequence homology to the S. termitidis type strain NCTC 11300(T), from which it, nevertheless, differed with respect to rep and rep- and RAPD-PCR profiles. An affiliation of the lemur isolate described in this study with the type strain of S. termitidis as well as a clear discrimination from other members of the Leptotrichiaceae could also be confirmed by matrix-assisted laser desorption/ionization time-of flight mass spectrometry and Fourier transform-infrared spectroscopy. This is the first evidence for clinical disease caused by S. termitidis in a vertebrate species indicating a broader host spectrum of this rarely encountered microorganism. PMID- 26377577 TI - Hyperglycemia-induced downregulation of apolipoprotein M expression is not via the hexosamine pathway. AB - BACKGROUND: We previously demonstrated that hyperglycemia could suppress apolipoprotein M (apoM) synthesis both in vivo and in vitro; however, the mechanism of hyperglycemia-induced downregulation of apoM expression is unknown yet. METHODS: In the present study we further examined if hexosamine pathway, one of the most important pathways of glucose turnover, being involved in modulating apoM expression in the hyperglycemia condition. We examined the effect of glucosamine, a prominent component of hexosamine pathway and intracellular mediator of insulin resistance, on apoM expression in HepG2 cells and in rat's models. In the present study we also determined apolipoprotein A1 (apoA1) as a control gene. RESULTS: Our results demonstrated that glucosamine could even up regulate both apoM and apoA1 expressions in HepG2 cell cultures. The glucosamine induced upregulation of apoM expression could be blocked by addition of azaserine, an inhibitor of hexosamine pathway. Moreover, intravenous infusion of glucosamine could enhance hepatic apoM expression in rats, although serum apoM levels were not significantly influences. CONCLUSIONS: It is concluded that both exogenous and endogenous glucosamine were essential for the over-expression of apoM, which may suggest that the increased intracellular content of glucosamine does not be responsible for the depressed apoM expression at hyperglycemia condition. PMID- 26377578 TI - Lumbar multifidus muscle changes in unilateral lumbar disc herniation using magnetic resonance imaging. AB - OBJECTIVE: To assess multifidus muscle asymmetry using the cross-sectional area (CSA) and perpendicular distance of the multifidus muscle to the lamina (MLD) measurements in patients with nerve compression due to lumbosacral disc hernia. MATERIALS AND METHODS: In total, 122 patients who underwent microdiscectomy for unilateral radiculopathy caused by disc herniation, diagnosed by magnetic resonance imaging (MRI), were evaluated retrospectively. Posterolateral or foraminal disc herniation at only one disc level, the L3-4, L4-L5, or L5-S1 region, was confirmed using MRI. Subjects were divided by symptom duration: 1-30 days, (group A), 31-90 days (group B), and > 90 days (group C). There were 48 cases in group A, 26 in group B, and 48 in group C. RESULTS: In groups A, B, and C, the median MLD differed significantly between the diseased and normal sides (P < 0.05). The MLD increased on the diseased side with symptom duration by lumbar disc herniation. The diseased side MLD was 5.1, 6.7, and 7.6 mm in groups A, B, and C, respectively (P < 0.05). The cut-off values for the MLD measurements were 5.3 mm (sensitivity = 62.3%, specificity = 55.5%; P < 0.05). In groups A, B, and C, the median CSA of the multifidus muscle was not significantly different between the diseased and the normal side (P > 0.05). CONCLUSIONS: The MLD measurement correlated significantly with multifidus asymmetry in patients with lumbar disc herniation. PMID- 26377579 TI - Biochemical imaging of cervical intervertebral discs with glycosaminoglycan chemical exchange saturation transfer magnetic resonance imaging: feasibility and initial results. AB - OBJECTIVE: To evaluate glycosaminoglycan chemical exchange saturation transfer (gagCEST) imaging at 3T in the assessment of the GAG content of cervical IVDs in healthy volunteers. MATERIALS AND METHODS: Forty-two cervical intervertebral discs of seven healthy volunteers (four females, three males; mean age: 21.4 +/- 1.4 years; range: 19-24 years) were examined at a 3T MRI scanner in this prospective study. The MRI protocol comprised standard morphological, sagittal T2 weighted (T2w) images to assess the magnetic resonance imaging (MRI) based grading system for cervical intervertebral disc degeneration (IVD) and biochemical imaging with gagCEST to calculate a region-of-interest analysis of nucleus pulposus (NP) and annulus fibrosus (AF). RESULTS: GagCEST of cervical IVDs was technically successful at 3T with significant higher gagCEST values in NP compared to AF (1.17% +/- 1.03% vs. 0.79% +/- 1.75%; p = 0.005). We found topological differences of gagCEST values of the cervical spine with significant higher gagCEST effects in lower IVDs (r = 1; p = 0). We could demonstrate a significant, negative correlation between gagCEST values and cervical disc degeneration of NP (r = -0.360; p = 0.019). Non-degenerated IVDs had significantly higher gagCEST effects compared to degenerated IVDs in NP (1.76% +/ 0.92% vs. 0.52% +/- 1.17%; p < 0.001). CONCLUSION: Biochemical imaging of cervical IVDs is feasible at 3T. GagCEST analysis demonstrated a topological GAG distribution of the cervical spine. The depletion of GAG in the NP with increasing level of morphological degeneration can be assessed using gagCEST imaging. PMID- 26377580 TI - Survival analysis of diagnostic assays in Plasmodium falciparum malaria. AB - BACKGROUND: Rapid diagnostic tests (RDT) and real-time PCR (qPCR) assays are sensitive for diagnosing malaria, but because they detect antigen and DNA, respectively, positivity may not reflect active infection. Performance characteristics of RDT and qPCR in Plasmodium falciparum positive specimens were evaluated over time to elucidate duration of positivity following conversion to microscopy negative. METHODS: Specimens from patients with at least one specimen that was positive for P. falciparum by microscopy, and at least one specimen that was negative for P. falciparum within a 1-month period were identified. Survival distributions of the diagnostic tests over time were compared. Performance characteristics for each test were calculated. RESULTS: Ninety specimens were included, with 48 initially positive for P. falciparum, and 42 subsequently negative. Of 42 specimens that converted to microscopy-negative following an initial positive, 26 (61.9 %) and 41 (97.6 %) were positive by qPCR and RDT, respectively. Survival curves of microscopy versus qPCR, as well as microscopy vs RDT differed significantly (p = 0.0002 and p < 0.0001, respectively). Compared to microscopy, sensitivity of qPCR was 100.0 % (95 % CI 90.8-100.0 %), and that of RDT was 100.0 % (95 % CI 90.8-100.0 %). CONCLUSIONS: Due to slow clearance of circulating antigen and DNA from bloodstream, RDT and qPCR have low positive predictive value for clinically relevant asexual parasitaemia in post-treatment specimens. Thus, microscopy remains the only available malaria diagnostic that can reliably distinguish true asexual parasitaemia from prolonged clearance of antigen and nucleic acid in a convalescing patient. PMID- 26377582 TI - Rapid nonlinear bladder and bowel evacuation: an evolutionary survival mechanism? PMID- 26377581 TI - Evaluation and management of perianal abscess and anal fistula: a consensus statement developed by the Italian Society of Colorectal Surgery (SICCR). AB - Perianal sepsis is a common condition ranging from acute abscess to chronic fistula formation. In most cases, the source is considered to be a non-specific cryptoglandular infection starting from the intersphincteric space. The key to successful treatment is the eradication of the primary track. As surgery may lead to a disturbance of continence, several sphincter-preserving techniques have been developed. This consensus statement examines the pertinent literature and provides evidence-based recommendations to improve individualized management of patients. PMID- 26377583 TI - The treatment of pilonidal disease: guidelines of the Italian Society of Colorectal Surgery (SICCR). AB - The Italian Society of Colorectal Surgery (SICCR.) has prepared clinical practice guidelines to help its members to optimize the treatment of pilonidal disease, a very common condition, especially among young people, and therefore of great importance on a socioeconomic level. The SICCR committee of experts on pilonidal disease analyzed the international literature and evaluated current evidence. Nonoperative management includes gluteal cleft shaving, laser epilation as well as fibrin glue and phenol injection: reported healing rates and recurrence incidence are satisfactory but the majority of studies are small series with low quality evidence. Surgical therapy which can be divided into two categories: excision of diseased tissue with primary closure using different techniques or excision with healing by secondary intention. On the whole, no clear benefit is demonstrated for one technique over the other. PMID- 26377585 TI - Biofilm, pathogenesis and prevention--a journey to break the wall: a review. AB - Biofilms contain group(s) of microorganisms that are found to be associated with the biotic and abiotic surfaces. Biofilms contain either homogenous or heterogeneous populations of bacteria which remain in the matrix made up of extracellular polymeric substances secreted by constituent population of the biofilm. Biofilms can be either single or multilayered. Biofilms are an increasing issue of concern that is gaining importance with each passing day. Due to the ubiquitous nature of biofilms, it is difficult to eradicate them. It has been seen that many infectious diseases harbour biofilms of bacterial pathogens as the reservoir of persisting infections which can prove fatal at times. The presence of biofilms can be seen in diseases like endocarditis, cystic fibrosis, periodontitis, rhinosinusitis and osteomyelitis. The presence of biofilms has been mostly seen in medical implants and urinary catheters. Various signalling events including two-component signalling, extra cytoplasmic function and quorum sensing are involved in the formation of biofilms. The presence of an extracellular polymeric matrix in biofilms makes it difficult for the antimicrobials to act on them and make the bacteria tolerant to antibiotics and other drugs. The aim of this review was to discuss about the basic formation of a biofilm, various signalling cascades involved in biofilm formation, possible mechanisms of drug resistance in biofilms and recent therapeutic approaches involved in successful eradication of biofilms. PMID- 26377586 TI - Carotenoid production and gene expression in an astaxanthin-overproducing Xanthophyllomyces dendrorhous mutant strain. AB - The primary carotenoid synthesized by Xanthophyllomyces dendrorhous is astaxanthin, which is used as a feed additive in aquaculture. Cell growth kinetics and carotenoid production were correlated with the mRNA levels of the idi, crtE, crtYB, crtI, crtS and crtR genes, and the changes in gene sequence between the wild-type and a carotenoid overproducer XR4 mutant strain were identified. At the late stationary phase, the total carotenoid content in XR4 was fivefold higher than that of the wild-type strain. Additionally, the mRNA levels of crtE and crtS increased during the XR4 growth and were three times higher than the wild-type strain in the late stationary phase. Moreover, the nucleotide sequences of crtYB, crtI and crtR exhibited differences between the strains. Both the higher crtE and crtS transcript levels and the crtYB, crtI and crtR mutations can, at least in part, act to up-regulate the carotenoid biosynthesis pathway in the XR4 strain. PMID- 26377587 TI - Osseointegration of Zirconia in the Presence of Multinucleated Giant Cells. AB - BACKGROUND: Current strategies to reduce medical device-associated infections propose zirconia as a potential implant material which may limit bacterial adhesion. Because multinucleated giant cells (MNGCs) have been detected on these implant surfaces, concerns have been raised regarding tissue integration. PURPOSE: The present study examined the presence of MNGCs and their subsequent effect upon tissue integration. Surface-modified implants made of yttria stabilized (TZP) and alumina-toughened zirconia (ATZ) were compared with commercially pure titanium (Ti). MATERIALS AND METHODS: Seven miniature pigs received three implants on either side of the maxilla. After healing periods of 4 and 8 weeks, the tissue response at the implant surfaces was characterized according to three specific parameters: bone-to-implant contact (BIC), MNGC-to implant contact (MIC), and the peri-implant bone density (BD). RESULTS: Despite being present on all tested implant surfaces, MNGCs were not associated with an inflammatory cell infiltrate or with fibrous encapsulation. MNGCs were less numerous on the Ti implants (range: 3.9-5.2%) compared with the ceramic implants (range: 17.6-30.3%, p < .0001). Even though the values of newly formed bone and pristine bone in direct contact with the implant surfaces were high at 4 weeks (tBIC: Ti = 82.3%, TZP = 64.3%, ATZ = 70%), a negative correlation was observed between the presence of MNGCs and newly formed bone at the implant surface (p < .001). Interestingly, the newly formed peri-implant bone density, defined as the percentage of new bone area inside the screw threads (nBD), was not diminished by the presence of MNGCs. CONCLUSIONS: Differences in the presence of MNGCs and the BIC parameters between Ti and the ceramic implants appear to be a local cellular phenomenon which is restricted to the implant-bone marrow interface and do not affect the peri-implant bone formation. Factors triggering MNGC differentiation and their persistence in response to biomaterial surface need to be investigated in future studies. PMID- 26377584 TI - Practice parameters for the treatment of colonic diverticular disease: Italian Society of Colon and Rectal Surgery (SICCR) guidelines. AB - The mission of the Italian Society of Colorectal Surgery (SICCR) is to optimize patient care. Providing evidence-based practice guidelines is therefore of key importance. About the present report it concernes the SICCR practice guidelines for the diagnosis and treatment of diverticular disease of the colon. The guidelines are not intended to define the sole standard of care but to provide evidence-based recommendations regarding the available therapeutic options. PMID- 26377588 TI - Microbial Attachment Inhibition through Low-Voltage Electrochemical Reactions on Electrically Conducting Membranes. AB - Bacterial biofilm formation on membrane surfaces remains a serious challenge in water treatment systems. The impact of low voltages on microbial attachment to electrically conducting ultrafiltration membranes was investigated using a direct observation cross-flow membrane system mounted on a fluorescence microscope. Escherichia coli and microparticle deposition and detachment rates were measured as a function of the applied electrical potential to the membrane surface. Selecting bacteria and particles with low surface charge minimized electrostatic interactions between the bacteria and charged membrane surface. Application of an electrical potential had a significant impact on the detachment of live bacteria in comparison to dead bacteria and particles. Image analysis indicated that when a potential of 1.5 V was applied to the membrane/counter electrode pair, the percent of dead bacteria was 32+/-2.1 and 67+/-3.6% when the membrane was used as a cathode or anode, respectively, while at a potential of 1 V, 92+/-2.4% were alive. The application of low electrical potentials resulted in the production of low (MUM) concentrations of hydrogen peroxide (HP) through the electroreduction of oxygen. The electrochemically produced HP reduced microbial cell viability and increased cellular permeability. Exposure to low concentrations of electrochemically produced HP on the membrane surface prevents bacterial attachment, thus ensuring biofilm-free conditions during membrane filtration operations. PMID- 26377589 TI - Cabozantinib for the treatment of non-small cell lung cancer with KIF5B-RET fusion. An example of swift repositioning. AB - A new chimeric fusion transcript of KIF5B (the kinesin family 5B gene) and the RET (Rearranged during Transcription) oncogene, KIF5B-RET, was found in 1-2% of lung adenocarcinomas (LADCs) in 2012. Several related clinical trials for non small cell lung cancer (NSCLC) with KIF5B-RET rearrangements using existing RET inhibitors, such as cabozantinib, lenvatinib, vandetanib, sunitinib, ponatinib, and AUY922, have been swiftly initiated by the discovery of the KIF5B-RET fusion gene. Anti-RET activity and the status of clinical development of cabozantinib for KIF5B-RET fusion-positive NSCLC are discussed. PMID- 26377590 TI - Phase I dose escalation and pharmacokinetic evaluation of two different schedules of LY2334737, an oral gemcitabine prodrug, in patients with advanced solid tumors. AB - BACKGROUND: This Phase-I-study aimed to determine the recommended Phase-II-dosing schedule of LY2334737, an oral gemcitabine prodrug, in patients with advanced/metastatic solid tumors. Pharmacokinetics, cytokeratin-18 (CK18) levels, genetic polymorphisms, and antitumor activity were additionally evaluated. METHODS: Patients received escalating doses of LY2334737 either every other day for 21 days (d) followed by 7 days-drug-free period (QoD-arm) or once daily for 7 days every other week (QD-arm). The 28 days-cycles were repeated until disease progression or unacceptable toxicity. Standard 3 + 3 dose-escalation was succeeded by a dose-confirmation phase (12 additional patients to be enrolled on the maximum tolerated dose [MTD]). RESULTS: Forty-one patients received QoD- (40 100 mg) and 32 QD-dosing (40-90 mg). On QoD, 3/9 patients experienced dose limiting toxicities (DLTs) on the 100 mg dose (2 * G3 diarrhea, 1 * G3 transaminase increase); 1 additional DLT (G3 diarrhea) occurred during dose confirmation at 90 mg (12 patients). On QD, 1 patient each experienced DLTs on 60 mg (G3 transaminase increase) and 80 mg (G3 prolonged QTcF-interval); 2/7 patients had 3 DLTs on the 90 mg dose (diarrhea, edema, liver-failure; all G3). The MTD was established at 90 mg for the QoD-arm. Seven patients on QoD and 4 on QD achieved SD (no CR + PR). Pharmacokinetics showed a dose-proportional increase in exposure of LY2334737 and dFdC without accumulation after repeated dosing. Significant increases in CK18 levels were observed. Genetic polymorphism of the cytidine deaminase gene (rs818202) could be associated with >= G3 hepatotoxicity. CONCLUSIONS: Both schedules displayed linear pharmacokinetics and acceptable safety profiles. The recommended dose and schedule of LY2334737 for subsequent Phase-II-studies is 90 mg given QoD for 21 day. PMID- 26377591 TI - Knock-down of transcript abundance of a family of Kunitz proteinase inhibitor genes in white clover (Trifolium repens) reveals a redundancy and diversity of gene function. AB - The transcriptional regulation of four phylogenetically distinct members of a family of Kunitz proteinase inhibitor (KPI) genes isolated from white clover (Trifolium repens; designated Tr-KPI1, Tr-KPI2, Tr-KPI4 and Tr-KPI5) has been investigated to determine their wider functional role. The four genes displayed differential transcription during seed germination, and in different tissues of the mature plant, and transcription was also ontogenetically regulated. Heterologous over-expression of Tr-KPI1, Tr-KPI2, Tr-KPI4 and Tr-KPI5 in Nicotiana tabacum retarded larval growth of the herbivore Spodoptera litura, and an increase in the transcription of the pathogenesis-related genes PR1 and PR4 was observed in the Tr-KPI1 and Tr-KPI4 over-expressing lines. RNA interference (RNAi) knock-down lines in white clover displayed significantly altered vegetative growth phenotypes with inhibition of shoot growth and a stimulation of root growth, while knock-down of Tr-KPI1, Tr-KPI2 and Tr-KPI5 transcript abundance also retarded larval growth of S. litura. Examination of these RNAi lines revealed constitutive stress-associated phenotypes as well as altered transcription of cellular signalling genes. These results reveal a functional redundancy across members of the KPI gene family. Further, the regulation of transcription of at least one member of the family, Tr-KPI2, may occupy a central role in the maintenance of a cellular homeostasis. PMID- 26377592 TI - Intake and sources of added sugars among Australian children and adolescents. AB - PURPOSE: To examine the intake and sources of added sugars (AS) of Australian children and adolescents, and compare their intake of free sugars (FS) to the recommended limit set by the World Health Organization (<10 % energy from FS). METHOD: Data of 4140 children and adolescents aged 2-16 years with plausible intakes based on 2 * 24 h recalls from the 2007 Australian National Children Nutrition and Physical Activity Survey were used. AS content of foods was estimated based on a published method. Intakes of AS and FS, as well as food sources of AS, were calculated. One-way ANOVA was used for comparisons between age groups and gender. RESULTS: The mean (SD) AS intake was 58.9 (35.1) g/day, representing 11.9 (5.6) % of daily energy intake and 46.9 (17.5) % of daily total sugars intake. More than 80 % of the subjects had % energy from FS > 10 %. Significant increasing trends for AS intake, % energy from AS, % energy from FS across age groups were observed. Sugar-sweetened beverages (19.6 %), cakes, biscuits, pastries and batter-based products (14.3 %), and sugar and sweet spreads (10.5 %) were the top three contributors of AS intake in the whole sample. Higher contribution of AS from sugar-sweetened beverages was observed in adolescents (p trend < 0.001). CONCLUSIONS: A large proportion of Australian youths are consuming excessive amounts of energy from AS. Since the main sources of AS were energy-dense, nutrient-poor foods, interventions which target the reduction in these foods would reduce energy and AS intake with minimal impact to core nutrient intake. PMID- 26377593 TI - High hemoglobin A1c variability is associated with early risk of microalbuminuria in children with T1D. AB - OBJECTIVE: To test the hypothesis that HbA1c variability, as measured by standard deviation (SD), is associated with increased risk for incident microalbuminuria and persistent microalbuminuria in pediatric type 1 diabetes (T1D). METHODS: A retrospective analysis using data from electronic health records was performed on 1195 patients from a pediatric diabetes clinic network in the Midwest USA from 1993 to 2009 with >=1 yr of T1D, >=4 total HbA1c values, >=2 HbA1c values/yr, >=1 urine microalbumin. Microalbuminuria, the main outcome was defined as albumin excretion rate >=20 mcg/min or 2 of 3 consecutive urine microalbumin/creatinine >=30 mg/gm. Patients who had persistently high microalbumin or who were treated with an angiotensin-converting-enzyme inhibitor within 1 yr were considered to have persistent microalbuminuria. Sex, race, age, diagnosis age, and duration were covariates. RESULTS: Median numbers of per-patient HbA1c and microalbumin results were 14 and 3, respectively. Median intrapersonal mean HbA1c and SD were 8.62% (70.72 mol/mol) and 1.47% (16.07 mmol/mol), respectively. The median interquartile range (IQR) of diagnosis age was 9.4 yr (6.26-12.02) and diabetes duration was 4.97 yr (2.93-7.64). A total of 172 patients (14.4%) developed microalbuminuria; 55 (4.6%) had persistent microalbuminuria. Patients with higher SD of HbA1c had shorter time to microalbuminuria. In time-dependent Cox Proportional Hazard models, updated SD of HbA1c was significantly associated with microalbuminuria [univariate hazard ratio (HR) 1.48 (1.25-1.76); multivariable HR 1.28 (1.04-1.58)], whereas updated mean HbA1c was not [univariate HR 1.08 (0.97 1.22); multivariable HR 1.05 (0.92-1.2)]. Patients with persistent microalbuminuria had similar HRs. CONCLUSIONS: HbA1c variability is independently associated with development of microalbuminuria in children with T1D, highlighting the importance of maintaining stable glycemic control in pediatric patients. PMID- 26377594 TI - Practical isolation of polygodial from Tasmannia lanceolata: a viable scaffold for synthesis. AB - Polygodial, a valuable sesquiterpene dialdehyde featuring an epimerizable stereocenter was efficiently extracted and isolated in gram-scale quantities (3.3% w/w) from Tasmannia lanceolata (Tasmanian native pepper) via a recently developed rapid pressurised hot water extraction (PHWE) technique that utilises an unmodified household espresso machine. This method was compared to the maceration of T. lanceolata under a range of conditions. Polygodial was used to achieve semi-syntheses of closely related sesquiterpene natural products drimendiol, (-)-drimenol, (+)-euryfuran, and some non-natural derivatives. PMID- 26377595 TI - Psychological and Personality Predictors of Weight Loss and Comorbid Metabolic Changes After Bariatric Surgery. AB - Bariatric surgery (BS) has proven to be the most effective treatment for weight loss and for improving comorbidities in severe obesity. A comprehensive psychological assessment prior to surgery is proposed to prepare patients for a successful post-surgical outcome. Therefore, the main aim of the present study was to assess psychological and personality predictors of BS outcome. The sample comprised 139 severely obese patients who underwent BS. Assessment measures included the Eating Disorders Inventory-2, the Symptom Checklist-Revised and the Temperament and Character Inventory-Revised. Our results show that favourable BS outcome, after 2 years follow up, was associated with younger age, less depression, moderate anxiety symptoms and high cooperativeness levels. Likewise, metabolic improvements were found to be linked to younger age and certain psychopathological factors. In conclusion, our findings suggest that age, baseline body mass index, psychopathological indexes and personality traits predict successful BS outcome. PMID- 26377596 TI - Proposing a Pedigree Risk Measurement Strategy: Capturing the Intergenerational Transmission of Antisocial Behavior in a Nationally Representative Sample of Adults. AB - An impressive literature has revealed that variation in virtually every measurable phenotype is the result of a combination of genetic and environmental influences. Based on these findings, studies that fail to use genetically informed modeling strategies risk model misspecification and biased parameter estimates. Twin- and adoption-based research designs have frequently been used to overcome this limitation. Despite the many advantages of such approaches, many available datasets do not contain samples of twins, siblings or adoptees, making it impossible to utilize these modeling strategies. The current study proposes a measurement strategy for estimating the intergenerational transmission of antisocial behavior (ASB) within a nationally representative sample of singletons using an extended pedigree risk approach that relies on information from first- and second-degree relatives. An evaluation of this approach revealed a pattern of findings that directly aligned with studies examining ASB using more traditional twin- and adoption-based research designs. While the proposed pedigree risk approach is not capable of effectively isolating genetic and environmental influences, this overall alignment in results provides tentative evidence suggesting that the proposed pedigree risk measure effectively captures genetic influences. Future replication studies are necessary as this observation remains preliminary. Whenever possible, more traditional quantitative genetic methodologies should be favored, but the presented strategy remains a viable alternative for more limited samples. PMID- 26377598 TI - Is there more than one way to unpack a Weibel-Palade body? PMID- 26377597 TI - Phase 2 study of frontline brentuximab vedotin monotherapy in Hodgkin lymphoma patients aged 60 years and older. AB - Outcomes in older patients with Hodgkin lymphoma (HL) tend to be poor following conventional chemotherapy regimens. Treatment-related toxicity is significant and comorbidities often limit therapeutic options. This phase 2, open-label study evaluated the efficacy and safety of brentuximab vedotin, a CD30-directed antibody-drug conjugate, as frontline therapy in 27 HL patients aged >=60 years. The objective response rate (ORR) was 92%, with 73% achieving complete remission. All patients achieved stable disease or better, and had decreased tumor volume following treatment. At the time of this analysis, the median duration of objective response for efficacy-evaluable patients (N = 26) was 9.1 months (range, 2.8 to 20.9+ months), median progression-free survival was 10.5 months (range, 2.6+ to 22.3+ months), and median overall survival had not been reached (range, 4.6+ to 24.9+ months). The observed adverse events (AEs) were generally consistent with the known safety profile of brentuximab vedotin. The most common AEs were peripheral sensory neuropathy (78%), fatigue (44%), and nausea (44%), and were <= grade 2 for most patients. The incidence of grade 3 peripheral neuropathy events was relatively high (30% overall), particularly among patients with the known risk factors of diabetes and/or hypothyroidism (46% vs 14% for those without). However, these risk factors were not associated with delayed time to resolution/improvement of peripheral neuropathy. Preliminary data showed no substantial age-related changes in brentuximab vedotin pharmacokinetics. Brentuximab vedotin monotherapy may provide a frontline treatment option for older patients who cannot tolerate conventional combination chemotherapy. This trial was registered at www.clinicaltrials.gov as #NCT01716806. PMID- 26377599 TI - Neurospora discreta as a model to assess adaptation of soil fungi to warming. AB - BACKGROUND: Short-term experiments have indicated that warmer temperatures can alter fungal biomass production and CO2 respiration, with potential consequences for soil C storage. However, we know little about the capacity of fungi to adapt to warming in ways that may alter C dynamics. Thus, we exposed Neurospora discreta to moderately warm (16 degrees C) and warm (28 degrees C) selective temperatures for 1500 mitotic generations, and then examined changes in mycelial growth rate, biomass, spore production, and CO2 respiration. We tested the hypothesis that strains will adapt to its selective temperature. Specifically, we expected that adapted strains would grow faster, and produce more spores per unit biomass (i.e., relative spore production). In contrast, they should generate less CO2 per unit biomass due to higher efficiency in carbon use metabolism (i.e., lower mass specific respiration, MSR). RESULTS: Indeed, N. discreta adapted to warm temperatures, based on patterns of relative spore production. Adapted strains produced more spores per unit biomass than parental strains in the selective temperature. Contrary to our expectations, this increase in relative spore production was accompanied by an increase in MSR and a reduction in mycelial growth rate and biomass, compared to parental strains. CONCLUSIONS: Adaptation of N. discreta to warm temperatures may have elicited a tradeoff between biomass production and relative spore production, possibly because relative spore production required higher MSR rates. Therefore, our results do not support the idea that adaptation to warm temperatures will lead to a more efficient carbon use metabolism. Our data might help improve climate change model simulations and provide more concise predictions of decomposition processes and carbon feedbacks to the atmosphere. PMID- 26377600 TI - Alpha-Catulin Co-Localizes With Vimentin Intermediate Filaments and Functions in Pulmonary Vascular Endothelial Cell Migration via ROCK. AB - The ubiquitous alpha-catulin acts as a scaffold for distinct signalosomes including RhoA/ROCK; however, its function is not well understood. While alpha catulin has homology to the cytoskeletal linkers alpha-catenin and vinculin, it appears to be functionally divergent. Here we further investigated alpha-catulin function in pulmonary vascular endothelial cells (VEC) on the premise that alpha catulin has a unique cytoskeletal role. Examination of endogenous alpha-catulin intracellular localization by immunofluorescence revealed a highly organized cytosolic filamentous network suggestive of a cytoskeletal system in a variety of cultured VEC. Double-immunofluorescence analyses of VEC showed endogenous alpha catulin co-localization with vimentin intermediate filaments. Similar to vimentin, alpha-catulin was found to distribute into detergent-soluble and insoluble fractions. Treatment of VEC with withaferinA, an agent that targets vimentin filaments, disrupted the alpha-catulin network distribution and altered alpha-catulin solubility. Vimentin participates in cell migration, and withaferinA was found to inhibit VEC migration in vitro; similarly, alpha-catulin knock-down reduced VEC migration. Based on previous reports showing that ROCK modulates vimentin, we found that ROCK depletion attenuated VEC migration; furthermore, alpha-catulin depletion was shown to reduce ROCK-induced signaling. These findings indicate that alpha-catulin has a unique function in co localization with vimentin filaments that contributes to VEC migration via a pathway that may involve ROCK signaling. J. Cell. Physiol. 231: 934-943, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26377601 TI - Readmission rates among cardiology inpatients with echocardiography abnormalities associated with heart failure. AB - BACKGROUND: Heart failure is a condition associated with significant morbidity. It is caused by structural or functional abnormalities of the heart. Many of these abnormalities if detected and managed early would prevent the onset of heart failure. AIMS: The aim of this study was to to determine the usefulness of echocardiography as a means of predicting readmission rates. A secondary aim was to profile patients with echocardiography abnormalities. METHODS: This was a prospective cohort study that followed patients over 36 months. Data were abstracted from the medical records of 76 cardiology patients in a large urban teaching hospital between 1.6.11 and 31.8.14. The outcome of interest was the number of readmissions occurring up to 48 months after discharge. We also aimed to profile these patients in terms of their co-morbidities and their medication history. RESULTS: Of those patients who had echocardiography (n = 447), 76 were considered to have a cardiac disorder (HHD, VHD, or LVSD) (n = 29). The mean readmission rate for HHD was 0.82, LVSD 0.62, and HHD 0.98. Patients with HHD were associated with a higher readmission rate of 1.8980 and for LVSD-1.24 times more likely. Those with a cardiac disorder were 13 % more likely to have a readmission within the next 36 months than those without a cardiac disorder. CONCLUSIONS: A significant proportion of patients were found to have a cardiac disorder related to HF. Echocardiographic abnormalities were shown to be an independent risk factor for readmission. PMID- 26377602 TI - Homemade laparoscopic surgical simulator: a cost-effective solution to the challenge of acquiring laparoscopic skills? AB - BACKGROUND: Laparoscopic surgery is well known to have a long and variable learning curve and there is a potential benefit from earlier integration of laparoscopic skills in medical education. AIMS: The aim of this study was to assess the challenges facing surgical trainees regarding the acquisition of laparoscopic skills and second to assess their opinion regarding the use of a homemade laparoscopic surgical simulator. METHODS: A homemade laparoscopic surgical simulator (HLSS) was constructed. An online survey using Survey Monkey(r) of surgical trainees at a tertiary referral university teaching hospital was conducted assessing their experience with laparoscopic surgery. Surgical trainees were voluntarily enrolled to assess the self-designed laparoscopic trainer. Each trainee was asked to perform simple exercises without supervision. RESULTS: All trainees (n = 34) responded to the survey. No trainee had full-time access to a laparoscopic box trainer. The mean time spent per week using the simulator was 0.38 h (range 0-3 h), with 61.8 % (n = 21) reporting not using the simulator at all. 94.1 % (n = 32) enrolled in our study. 90.6 % (n = 29) found the HLSS easy to use compared to 93.8 % (n = 30) with the CLS (p = 1.00). 96.9 % (n = 31) reported an overall satisfaction with the HLSS. There was no difference with regard to the completing the tasks: peg transfer (78.1 vs 78.1 %, p = 1.00), cutting patterns (65.6 vs 71.9 %, p = 0.788) or knot tying (12.5 vs 18.8 %, p = 0.732) whether using HLSS and the CLS. CONCLUSION: Homemade laparoscopic surgical simulators are easy to construct, affordable, usable and of interest to trainees. PMID- 26377604 TI - Reducing the layer number of AB stacked multilayer graphene grown on nickel by annealing at low temperature. AB - Controlling the number of layers of graphene grown by chemical vapor deposition is crucial for large scale graphene application. We propose here an etching process of graphene which can be applied immediately after growth to control the number of layers. We use nickel (Ni) foil at high temperature (T = 900 degrees C) to produce multilayer-AB-stacked-graphene (MLG). The etching process is based on annealing the samples in a hydrogen/argon atmosphere at a relatively low temperature (T = 450 degrees C) inside the growth chamber. The extent of etching is mainly controlled by the annealing process duration. Using Raman spectroscopy we demonstrate that the number of layers was reduced, changing from MLG to few layer-AB-stacked-graphene and in some cases to randomly oriented few layer graphene near the substrate. Furthermore, our method offers the significant advantage that it does not introduce defects in the samples, maintaining their original high quality. This fact and the low temperature our method uses make it a good candidate for controlling the layer number of already grown graphene in processes with a low thermal budget. PMID- 26377603 TI - Pyogenic liver abscess after gunshot injury: 10 years' experience at a single level 1 trauma center. AB - OBJECTIVES: Liver abscesses are approximately 50 % of all visceral abscesses, and trauma presents as a rare cause of the liver abscess. Otherwise, hepatic abscess is an uncommon complication of gunshot wound (GSW) to the liver among all trauma cases. Here we reviewed their experience in detail. METHOD: From January 1, 2004 to September 30, 2013, there were 2143 patients admitted to Ryder Trauma Center at Jackson Memorial Hospital/University of Miami with severe abdominal trauma: 1227 penetrating and 866 blunt. Among the patients who had penetrating trauma, 637 had GSWs and 551 had stab wounds. Thirty-nine patients had other kinds of penetrating traumas. Eleven patients were identified as having liver abscess, with 8 of them belonging to the GSW group, and 3 to the blunt injury group. The diagnosis and management of the 8 patients with a hepatic abscess after GSW to the liver were demonstrated. RESULT: There were seven males and one female with a mean age of 29 +/- 10 years. There were one grade 2, four grade 3, two grade 4 and one grade 5 injuries. The mean abscess size was 10 +/- 2 cm. The abscesses were usually caused by infection from mixed organisms. These abscesses were treated with antibiotics and drainage. No mortality and long-term morbidity were seen. CONCLUSION: Hepatic abscess after GSW to the liver is a rare condition, with an incidence of 1.2 %. It is usually seen in severe liver injury (grade 3 and above), but our patients were all treated successfully, with no mortality. PMID- 26377605 TI - Robotically assisted percutaneous coronary intervention: benefits to the patient and the cardiologist. AB - Robotic percutaneous interventional systems represent the future of interventional cardiology. Robotic technology significantly reduces operator exposure to ionizing radiation, and improves ergonomics in the cardiac catheterization laboratory, thereby preventing orthopedic injuries. It may enable more accurate stent implantation and reduce the incidence of contrast-induced nephropathy. Robotics has the potential of converting the current 'high-risk' catheterization laboratory into a safe, physician- and patient-friendly environment. PMID- 26377606 TI - The Levels of Tissue Factor Pathway Inhibitor in Sepsis Patients Receiving Prophylactic Enoxaparin. AB - OBJECTIVE: Sepsis syndrome is usually accompanied by activation of blood coagulation mechanisms. Earlier studies found deficiencies of the 3 main natural anticoagulants, antithrombin, protein C, and protein S. However, none of these inhibitors block tissue factor, the prime trigger of coagulation during sepsis that is controlled specifically by the tissue factor pathway inhibitor (TFPI). The aim of this study was to characterize the fluctuations in the levels of natural anticoagulants, particularly TFPI, in the course of sepsis and to find out their association with the anticoagulant action of the low-molecular-weight heparin enoxaparin. MATERIALS AND METHODS: We studied 51 consecutive patients with sepsis. Blood samples were collected from patients at baseline (0 h) and at 4, 12, and 24 h after enoxaparin administration. The following assays were undertaken using commercial kits: activated partial thromboplastin time, prothrombin time, thrombin time, total and free TFPI, protein C and protein S, antithrombin, fibrinogen, and anti-factor Xa. RESULTS: Before enoxaparin administration, there was significant prolongation of the prothrombin time and activated partial thromboplastin time, and this remained the case in the 3 subsequent samples. There was marked reduction in the levels of antithrombin, protein C, and total and free protein S to below control values throughout the study. In contrast, plasma levels of both total and free TFPI were markedly elevated and increased after enoxaparin therapy. Anti-factor Xa levels were within the therapeutic range throughout. There was no difference in TFPI levels between those patients who died and those who survived. CONCLUSION: Sepsis triggered marked release of TFPI from endothelial cells. This persisted and was increased further following the administration of enoxaparin. In contrast, there was marked consumption of the natural coagulation inhibitors antithrombin, protein C, and protein S. These results go some way towards explaining why the therapeutic use of recombinant TFPI fails to correct sepsis-associated coagulopathy. PMID- 26377612 TI - 2'-Methoxyacetophenone: An Efficient Photosensitizer for Cyclobutane Pyrimidine Dimer Formation. AB - Stationary and time-resolved experiments show that 2'-methoxyacetophenone (2-M) is an interesting compound for the investigation of triplet states in thymine samples. Time-resolved emission experiments show that the fluorescence lifetime of 2-M is 660 ps. A similar time constant of 680 ps is found in transient IR experiments. The data indicate efficient intersystem crossing (~97%) from the fluorescent singlet state to the triplet state. The lifetime of the triplet state of 2-M dissolved in D2O at room temperature and ambient oxygen concentration is 400 ns. 2-M has a strong absorption in the UV-A range and can photosensitize the triplet state of a thymidine dinucleotide with light at a wavelength of 320 nm. The experiments show that 2-M is well-suited for time-resolved experiments on the triplet-sensitizing process. PMID- 26377607 TI - Characterization of the Binding Site of Aspartame in the Human Sweet Taste Receptor. AB - The sweet taste receptor, a heterodimeric G protein-coupled receptor comprised of T1R2 and T1R3, binds sugars, small molecule sweeteners, and sweet proteins to multiple binding sites. The dipeptide sweetener, aspartame binds in the Venus Flytrap Module (VFTM) of T1R2. We developed homology models of the open and closed forms of human T1R2 and human T1R3 VFTMs and their dimers and then docked aspartame into the closed form of T1R2's VFTM. To test and refine the predictions of our model, we mutated various T1R2 VFTM residues, assayed activity of the mutants and identified 11 critical residues (S40, Y103, D142, S144, S165, S168, Y215, D278, E302, D307, and R383) in and proximal to the binding pocket of the sweet taste receptor that are important for ligand recognition and activity of aspartame. Furthermore, we propose that binding is dependent on 2 water molecules situated in the ligand pocket that bridge 2 carbonyl groups of aspartame to residues D142 and L279. These results shed light on the activation mechanism and how signal transmission arising from the extracellular domain of the T1R2 monomer of the sweet receptor leads to the perception of sweet taste. PMID- 26377614 TI - Dimethylzinc-Initiated Radical Coupling of beta-Bromostyrenes with Ethers and Amines. AB - A new coupling reaction has been developed in which beta-bromostyrenes react with ethers and tertiary amines to introduce the styryl group in the alpha-position. The transformation is mediated by Me2 Zn/O2 with 10 % MnCl2 and is believed to proceed by a radical addition-elimination mechanism. The ether and the amine are employed as solvent and the coupling takes place through the most stable alpha radical for unsymmetrical substrates. The products are obtained in moderate to good yields as the pure E isomers. The coupling can be achieved with a range of smaller cyclic and acyclic ethers/amines as well as various substituted beta bromostyrenes. PMID- 26377613 TI - Variation in apparent diffusion coefficient measurements among women with locally advanced cervical cancer. AB - ADC variability from mixed data sets acquired from women with locally advanced cervical cancer appears to be predominantly of biologic origin. Intra-histology ADC variance was similar when pooled across technical factors. Inter-histology pooling increased ADC variance. Normalization to urine ADC improved intra histology variance and receiver-operator curve test performance. PMID- 26377615 TI - Silver nanoparticle based highly selective and sensitive solvatochromatic sensor for colorimetric detection of 1,4-dioxane in aqueous media. AB - A citrate stabilised silver nanoparticle (Ci-AgNP) based solvatochromic sensor, which functions as a highly selective and sensitive colorimetric probe for 1,4 dioxane in aqueous media is reported. The surfaces of the AgNPs generate reactive oxygen species, which promote the degradation of 1,4-dioxane assembled in the vicinity of the nanoparticle surfaces through charge transfer interactions. During this process, Ag(0) is oxidised to Ag(+) and the yellow colour of the solution turns to colourless. The sensor was used for the estimation of 1,4 dioxane in ground water and also 1,4-dioxane vapour diffused in aqueous media. PMID- 26377616 TI - Improvement of chiral stationary phases based on cinchona alkaloids bonded to crown ethers by chiral modification. AB - To improve the chiral recognition capability of a cinchona alkaloid crown ether chiral stationary phase, the crown ether moiety was modified by the chiral group of (1S, 2S)-2-aminocyclohexyl phenylcarbamate. Both quinine and quinidine-based stationary phases were evaluated by chiral acids, chiral primary amines and amino acids. The quinine/quinidine and crown ether provided ion-exchange sites and complex interaction site for carboxyl group and primary amine group in amino acids, respectively, which were necessary for the chiral discrimination of amino acid enantiomers. The introduction of the chiral group greatly improved the chiral recognition for chiral primary amines. The structure of crown ether moiety was proved to play a dominant role in the chiral recognitions for chiral primary amines and amino acids. PMID- 26377617 TI - Pharmacodynamic models of age-structured cell populations. AB - The purpose of this work is to review basic pharmacodynamic (PD) models describing drug effects on cell populations and expand them to age-structured models using the theory of physiologically structured populations. The plasma drug concentrations are interpreted as the environment affecting the cell production and mortality rates. An explicit solution to model equations provides the age density distribution that serves to establish a relationship between the cell lifespan distribution and the hazard of cell removal. Given the lifespan distributions, the age distributions for most commonly applied PD models of cell responses including basic cell turnover, transit compartments, and basic lifespan models have been derived both for the baseline conditions and drug treatment. The steady-state age distribution for basic indirect response models is exponential, and it is uniform for the basic lifespan model. As an example of more complex cell population, the age distribution of human red blood cells has been simulated based on a recent model of red blood cell survival. The age distribution for cells in the transit compartment model is the sum of the gamma functions. Means and variances of age distributions for all discussed models were calculated. A brief discussion of numerical challenges and possible future model developments is presented. PMID- 26377618 TI - A time series analysis of alcohol-related presentations to emergency departments in Queensland following the increase in alcopops tax. AB - BACKGROUND: Raising duty on alcohol across the board can reduce morbidity, mortality and other adverse consequences of alcohol use. However, effectiveness is less certain for measures that target specific types of alcohol beverage in isolation. One example from Australia was the increase in tax on alcopops favoured by young people to curb risky drinking in this demographic. METHODS: We measured alcohol-related health harms in 15-29-year-olds presenting to emergency departments (EDs) in Queensland following the tax increase. These presentations were compared with following ED controls: (1) 15-29-year-olds with asthma or appendicitis; and (2) 30-49-year-olds presenting with alcohol-related harms. We analysed data over a 5-year period (April 2005-April 2010) using a time series analysis. This covered 3 years before, and 2 years after, the tax increase. We investigated both mental and behavioural consequences (F10 codes), and intentional/unintentional injuries (S and T codes). RESULTS: We fitted an ARIMA (autoregressive integrated moving average) model to test for a change following the increased 'alcopops' tax in April 2008. There was no significant decrease in alcohol-related ED presentations in 15-29-year-olds compared to any of the controls. We found similar results for males and females, narrow and broad definitions of alcohol-related harms, under-19s and ED presentations at night time and weekends. CONCLUSIONS: The increase in tax on 'alcopops' did not result in any reduction in alcohol-related harms in this population. Targeting particular alcoholic drinks may therefore not be as effective as more comprehensive policies such as minimum unit pricing for alcohol. PMID- 26377619 TI - Megadosemethilprednisolone (mdmp) For Primary Myelofibrosis (pmf). PMID- 26377620 TI - Long-term treatment of relapsing-remitting multiple sclerosis with interferon beta: how strongly should we encourage patients to adhere to the 'old' therapies? PMID- 26377621 TI - Ab initio calculation of electronic charge mobility in metal-organic frameworks. AB - A density functional theory approach coupled with the Boltzmann transport equation within the relaxation time approximation was used to investigate the charge mobility for three MOF functionalization designs. The specific MOF investigated was a Zr-UiO-66 MOF with three functionalizations that included benzenedicarboxylate (BDC), BDC functionalized with an amino group (BDC + NH2), and BDC functionalized with a nitro group (BDC + NO2). Previous experimental studies have confirmed a 40% decrease in the optical band-gap with functionization; this study predicted an accompanying decrease in mobility by 14%. On the contrary, the charge density was found to increase with functionalization. The culmination of these two findings resulted in a predicted conductivity of approximately 3.8 * 10(-8) S cm(-1) for BDC design and decreasing less than 2% for other cases. Furthermore, band conduction was confirmed for this MOF design as a result of the de-localized pi electron of the carbon atoms along the organic linker. Overall, the functionalization proved to decrease mobility; however, it was evident that the functionalization has potential for tailoring the spectral layout of low lying unoccupied orbitals and ultimately the charge concentration, which could prove to be important for increasing the overall conductivity of MOFs. PMID- 26377623 TI - Insights triggered by textual micro-counseling dialogues of restructuring orientation in experts and students. AB - Insight is a salient psychotherapeutic progress but has rarely been measured in a controlled experimental setting. This study aimed to assess whether textual micro counseling dialogue could validly evoke insight and to explore the characteristics of insight. The guessing riddle of cognitive psychology was used as a reference of the experimental paradigm. Specifically, textual micro counseling dialogues applying cognitive restructuring techniques were presented. The participant first read a description of a psychological distress ("problem") and then an explanation ("solution"). Zero-, low-, and high-restructuring solutions were randomly matched to the problems and it was expected that they would trigger different levels of insight experiences. Experts and students evaluated the adaptability and emotional valence of problems, and the insightfulness, novelty, adaptability, and emotional valence of solutions. For both experts and students, different intensities of insightfulness were produced across high-, low- and zero-restructuring solutions. Novelty significantly discriminated the high-restructuring solutions from the other two solution types. Adaptability and emotional valence could discriminate the high- and low restructuring solutions types from the zero-restructuring solution. Insightfulness had high correlations with novelty and adaptability. These results indicated that textual micro-counseling dialogues with a high-restructuring solution could validly produce the greatest insightfulness and the features of high-restructuring solutions may have reference meaning for improving psychotherapeutic effect. PMID- 26377624 TI - Antibacterial Activities of Ankaferd Hemostat (ABS) on Shiga Toxin-Producing Escherichia coli and Other Pathogens Significant in Foodborne Diseases. AB - OBJECTIVE: Ankaferd hemostat (Ankaferd Blood Stopper(r), ABS)-induced pharmacological modulation of essential erythroid proteins can cause vital erythroid aggregation via acting on fibrinogen gamma. Topical endoscopic ABS application is effective in the controlling of gastrointestinal (GI) system hemorrhages and/or infected GI wounds. Escherichia coli O157:H7, the predominant serotype of enterohemorrhagic E. coli, is a cause of both outbreaks and sporadic cases of hemorrhagic colitis. The aim of this study is to examine the effects of ABS on 6 different Shiga toxigenic E. coli serotypes including O26, O103, O104, O111, O145, and O157 and on other pathogens significant in foodborne diseases, such as Salmonella Typhimurium, Campylobacter jejuni, and Listeria monocytogenes, were also assessed. MATERIALS AND METHODS: All strains were applied with different amounts of ABS and antimicrobial effect was screened. S. Typhimurium groups were screened for survival using the fluorescence in situ hybridization technique. RESULTS: The relative efficacy of ABS solutions to achieve significant logarithmic reduction in foodborne pathogens E. coli O157:H7 and non-O157 serogroups and other emerging foodborne pathogens is demonstrated in this study. ABS has antibacterial effects. CONCLUSION: Our present study indicated for the first time that ABS may act against E. coli O157:H7, which is a cause of thrombotic thrombocytopenic purpura, hemolytic-uremic syndrome, and hemorrhagic colitis. The interrelationships between colitis, infection, and hemostasis within the context of ABS application should be further investigated in future studies. PMID- 26377625 TI - Endophytic bacterial communities associated with two explant sources of Eucalyptus benthamii Maiden & Cambage. AB - Micropropagation has been applied in the recovery and rejuvenation of adult trees, which is achieved by various subcultures in the multiplication phase. This strategy has brought questions about the endophytic microbiota associated with these plants along its manipulation. Therefore, the aim of this study was to evaluate the composition of the endophytic bacterial communities associated with two explants sources [the canopy branches (CB) and the trunk base of the tree (TB)] under prolonged in vitro cultivation. In addition we analyzed the bacterial community dynamic along the subcultures in different micropropagation phases. Bacterial DNA was extracted from samples of mini-stumps (in vivo) from CB and TB and in micro-stumps produced by in vitro cultivations of these explants sources- both originated from one single matrix plant of Eucalyptus benthamii. In vitro establishment occurred in two dates and the evaluation of endophytic bacterial communities was made in vivo and in vitro samples (on 10th, 13th and 16th subcultures), when elongated shoots and roots were analyzed. Analysis was performed by PCR-DGGE based on the V6 region of ribosomal gene 16S rDNA. Bands profiles showed differences in communities between in vivo and in vitro samples, and also distinctions of communities assessed in the subcultures, elongated and rooted samples. Distinctions in the composition of endophytic bacterial communities were greater in CB micro-stumps. These results indicate a differential colonization of explants by endophytic bacteria, with predominance of common (ever-present) endophytes in TB samples and casual, here named opportunistic, in CB samples. PMID- 26377626 TI - Metacognitive monitoring during category learning: how success affects future behaviour. AB - The purpose of this study was to see how people perceive their own learning during a category learning task, and whether their perceptions matched their performance. In two experiments, participants were asked to learn natural categories, of both high and low variability, and make category learning judgements (CLJs). Variability was manipulated by varying the number of exemplars and the number of times each exemplar was presented within each category. Experiment 1 showed that participants were generally overconfident in their knowledge of low variability families, suggesting that they considered repetition to be more useful for learning than it actually was. Also, a correct trial, for a particular category, was more likely to occur if the previous trial was correct. CLJs had the largest increase when a trial was correct following an incorrect trial and the largest decrease when an incorrect trial followed a correct trial. Experiment 2 replicated these results, but also demonstrated that global CLJ ratings showed the same bias towards repetition. These results indicate that we generally identify success as being the biggest determinant of learning, but do not always recognise cues, such as variability, that enhance learning. PMID- 26377627 TI - Quantum dot multiplexing for the profiling of cellular receptors. AB - The profiling of cellular heterogeneity has wide-reaching importance for our understanding of how cells function and react to their environments in healthy and diseased states. Our ability to interpret and model cell behavior has been limited by the difficulties of measuring cell differences, for example, comparing tumor and non-tumor cells, particularly at the individual cell level. This demonstrates a clear need for a generalizable approach to profile fluorophore sites on cells or molecular assemblies on beads. Here, a multiplex immunoassay for simultaneous detection of five different angiogenic markers was developed. We targeted angiogenic receptors in the vascular endothelial growth factor family (VEGFR1, VEGFR2 and VEGFR3) and Neuropilin (NRP) family (NRP1 and NRP2), using multicolor quantum dots (Qdots). Copper-free click based chemistry was used to conjugate the monoclonal antibodies with 525, 565, 605, 655 and 705 nm CdSe/ZnS Qdots. We tested and performed colocalization analysis of our nanoprobes using the Pearson correlation coefficient statistical analysis. Human umbilical vein endothelial cells (HUVEC) were tested. The ability to easily monitor the molecular indicators of angiogenesis that are a precursor to cancer in a fast and cost effective system is an important step towards personalized nanomedicine. PMID- 26377629 TI - Piriformis Syndrome With Variant Sciatic Nerve Anatomy: A Case Report. AB - A 68-year-old male long distance runner presented with low back and left buttock pain, which eventually progressed to severe and debilitating pain, intermittently radiating to the posterior thigh and foot. A comprehensive workup ruled out possible spine or hip causes of his symptoms. A pelvic magnetic resonance imaging neurogram with complex oblique planes through the piriformis demonstrated variant anatomy of the left sciatic nerve consistent with the clinical diagnosis of piriformis syndrome. The patient ultimately underwent neurolysis with release of the sciatic nerve and partial resection of the piriformis muscle. After surgery the patient reported significant pain reduction and resumed running 3 months later. Piriformis syndrome is uncommon but should be considered in the differential diagnosis for buttock pain. Advanced imaging was essential to guide management. PMID- 26377628 TI - Interfacial thiol-isocyanate reactions for functional nanocarriers: a facile route towards tunable morphologies and hydrophilic payload encapsulation. AB - Functional nanocarriers were synthesized using an in situ inverse miniemulsion polymerization employing thiol-isocyanate reactions at the droplet interface to encapsulate hydrophilic payloads. The morphology of the nanocarriers is conveniently tunable by varying the reaction conditions and the dispersions are easily transferable to the aqueous phase. PMID- 26377630 TI - Omalizumab in patients with eosinophilic granulomatosis with polyangiitis: a 36 month follow-up study. AB - OBJECTIVE: Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic vasculitis characterized by asthma and blood eosinophilia, with the lung being the organ most frequently affected. Oral glucocorticoids and/or immunosuppressive drugs are the mainstay therapy of EGPA. Occasional reports suggest that EGPA patients can be treated with omalizumab in addition to conventional therapy to achieve asthma control. To investigate the long-term effects of omalizumab in patients with EGPA and asthma (2 females, 3 males, age 41-64 years), we carried out a 36-month follow-up observational study. At the time of enrollment, the patients were on maintenance therapy and had moderate to severe allergic asthma, eosinophilia and rhinosinusitis. Mononeuropathy/polyneuropathy and/or histological evidence of tissue eosinophilic infiltration were also present. METHODS: Patients were treated with omalizumab (300-600 mg s.c. every 2-4 weeks) as add-on therapy to prednisone, inhaled steroids and bronchodilators. During omalizumab treatment, spirometry, the asthma control test (ACT) score and eosinophilia were evaluated, and prednisone dosage was recorded. RESULTS: During the 36 months of omalizumab treatment asthma progressively improved as indicated by spirometry and the ACT score. Eosinophilia progressively decreased. The oral prednisone dose was reduced or withdrawn during treatment. No adverse events were recorded. CONCLUSIONS: In patients with EGPA and moderate to severe allergic asthma, omalizumab can be beneficial and safe. It enables corticosteroid tapering while decreasing eosinophilia and improving asthma symptoms over 36 months. PMID- 26377631 TI - Distinct functional consequences of MUTYH variants associated with colorectal cancer: Damaged DNA affinity, glycosylase activity and interaction with PCNA and Hus1. AB - MUTYH is a base excision repair (BER) enzyme that prevents mutations in DNA associated with 8-oxoguanine (OG) by catalyzing the removal of adenine from inappropriately formed OG:A base-pairs. Germline mutations in the MUTYH gene are linked to colorectal polyposis and a high risk of colorectal cancer, a syndrome referred to as MUTYH-associated polyposis (MAP). There are over 300 different MUTYH mutations associated with MAP and a large fraction of these gene changes code for missense MUTYH variants. Herein, the adenine glycosylase activity, mismatch recognition properties, and interaction with relevant protein partners of human MUTYH and five MAP variants (R295C, P281L, Q324H, P502L, and R520Q) were examined. P281L MUTYH was found to be severely compromised both in DNA binding and base excision activity, consistent with the location of this variation in the iron-sulfur cluster (FCL) DNA binding motif of MUTYH. Both R295C and R520Q MUTYH were found to have low fractions of active enzyme, compromised affinity for damaged DNA, and reduced rates for adenine excision. In contrast, both Q324H and P502L MUTYH function relatively similarly to WT MUTYH in both binding and glycosylase assays. However, P502L and R520Q exhibited reduced affinity for PCNA (proliferation cell nuclear antigen), consistent with their location in the PCNA binding motif of MUTYH. Whereas, only Q324H, and not R295C, was found to have reduced affinity for Hus1 of the Rad9-Hus1-Rad1 complex, despite both being localized to the same region implicated for interaction with Hus1. These results underscore the diversity of functional consequences due to MUTYH variants that may impact the progression of MAP. PMID- 26377632 TI - 'De novo' and 'recurrent' autoimmune hepatitis after liver transplantation: A comprehensive review. AB - Autoimmune Hepatitis (AIH) is a chronic progressive inflammatory disease of the liver that responds to immunosuppressive therapy. In patients with AIH who have an acute liver failure presentation or those who develop end stage liver disease despite medical therapy, liver transplantation (LT) may become necessary. Despite good outcomes after LT, AIH can develop/recur in the allograft with an estimated incidence of recurrence between 8 and 12% at 1 year and 36-68% at 5 years. The presence of non-organ specific autoantibodies, elevated serum aminotransferases and immunoglobulin G as well as the characteristic histologic features of interface hepatitis (peri-portal plasma cell infiltration) characterize recurrence of disease. De novo AIH is the development of features of classical AIH in the allograft of patients who have not been transplanted for AIH. There are several reports in the pediatric transplant population, where administering immunosuppressive therapy in the regimen used to treat AIH has stabilized graft function in de novo AIH. In adults, hepatitis C (HCV) is the most common indication for LT and HCV often recurs after LT, requiring treatment with Interferon and Ribavirin. Labeling the graft dysfunction 'de novo AIH' can be problematic in this context, particularly if HCV RNA is positive at that time. Some have chosen to give other names like 'graft dysfunction mimicking AIH' and 'plasma cell hepatitis'. Regardless of the nomenclature, autoimmune liver graft dysfunction, if managed appropriately with the treatment regimen used to treat AIH, can save grafts and patients. The mechanism causing recurrent or de novo AIH after LT remains unknown. Several mechanisms have been implicated in this loss of self-tolerance including impaired thymic regulation, impaired activity of T regulatory cells, molecular mimicry, calcineurin inhibitors, glutathione-s transferase and genetic polymorphisms. While the phenotype of de novo AIH in pediatrics has been uniform, it has been more variable in adults, highlighting the need for uniform diagnostic criteria or scoring system post LT. Better understanding of the development of autoimmunity and its difference from classical rejection after LT will allow better therapeutic strategies and improved outcome. PMID- 26377634 TI - A Remarkably Efficient MnFe2 O4 -based Oxidase Nanozyme. AB - Nanomaterials-based enzyme mimetics (nanozymes) have attracted considerable interest due to their applications in imaging, diagnostics, and therapeutic treatments. Particularly, metal-oxide nanozymes have been shown to mimic the interesting redox properties and biological activities of metalloenzymes. Here we describe an efficient synthesis of MnFe2 O4 nanomaterials and show how the morphology can be controlled by using a simple co-precipitation method. The nanomaterials prepared by this method exhibit a remarkable oxidase-like activity. Interestingly, the activity is morphology-dependent, with nanooctahedra (NOh) exhibiting a catalytic efficiency of 2.21*10(9) m(-1) s(-1) , the highest activity ever reported for a nanozyme. PMID- 26377633 TI - Brain endothelial dysfunction in cerebral adrenoleukodystrophy. AB - See Aubourg (doi:10.1093/awv271) for a scientific commentary on this article.X linked adrenoleukodystrophy is caused by mutations in the ABCD1 gene leading to accumulation of very long chain fatty acids. Its most severe neurological manifestation is cerebral adrenoleukodystrophy. Here we demonstrate that progressive inflammatory demyelination in cerebral adrenoleukodystrophy coincides with blood-brain barrier dysfunction, increased MMP9 expression, and changes in endothelial tight junction proteins as well as adhesion molecules. ABCD1, but not its closest homologue ABCD2, is highly expressed in human brain microvascular endothelial cells, far exceeding its expression in the systemic vasculature. Silencing of ABCD1 in human brain microvascular endothelial cells causes accumulation of very long chain fatty acids, but much later than the immediate upregulation of adhesion molecules and decrease in tight junction proteins. This results in greater adhesion and transmigration of monocytes across the endothelium. PCR-array screening of human brain microvascular endothelial cells after ABCD1 silencing revealed downregulation of both mRNA and protein levels of the transcription factor c-MYC (encoded by MYC). Interestingly, MYC silencing mimicked the effects of ABCD1 silencing on CLDN5 and ICAM1 without decreasing the levels of ABCD1 protein itself. Together, these data demonstrate that ABCD1 deficiency induces significant alterations in brain endothelium via c-MYC and may thereby contribute to the increased trafficking of leucocytes across the blood brain barrier as seen in cerebral adrenouleukodystrophy. PMID- 26377635 TI - Surgery for Type III-IV hiatal hernia: anatomical recurrence and global results after elective treatment of short oesophagus with open and minimally invasive surgery. AB - OBJECTIVES: Type III-IV hiatal hernia (HH) is associated with a true short oesophagus in more than 50% of cases; dedicated treatment of this condition might be appropriate to reduce the recurrence rate after surgery. A case series of patients receiving surgery for Type III-IV hernia was examined for short oesophagus, and the results were analysed. METHODS: From 1980 to 1994, 60 patients underwent an open surgical approach, and the position of the oesophago gastric junction was visually localized; from 1995 to 2013, 48 patients underwent a minimally invasive approach, and the oesophago-gastric junction was objectively localized using a laparoscopic-endoscopic method. The patients underwent a timed clinical-instrumental follow-up that included symptoms assessment, barium swallow and endoscopy. The results were considered to be excellent in the absence of symptoms and oesophagitis; good, if symptoms occurred two to four times a month in the absence of oesophagitis; fair, if symptoms occurred two to four times a week in the presence of hyperaemia, oedema and/or microscopic oesophagitis; and poor, if symptoms occurred on a daily basis in the presence of any grade of endoscopic oesophagitis, HH of any size or type, or the need for antireflux medical therapy. The follow-up time was calculated from the time of surgery to the last complete follow-up. RESULTS: Among the open surgery patients, 78% underwent abdominal fundoplication, 10% the Belsey Mark IV procedure, 8% laparotomic Collis-Nissen fundoplication and 3% the Pearson operation. Among the minimally invasive surgery patients, 44% underwent a laparoscopic floppy Nissen procedure and 56% a left thoracoscopic Collis-laparoscopic Nissen procedure. The postoperative mortality and complication rates were 1.6% (1/60) and 15% for open surgery and 4.1% (2/48) and 12.5% for minimally invasive surgery. A total of 105 patients were followed up for a median period of 96 months. Five relapses occurred after open surgery (5/59, 8%) and two after minimally invasive surgery (2/46, 4%). Among the 105 patients, excellent, good, fair and poor outcomes were observed in 38%, 44%, 9% and 9%, respectively. CONCLUSIONS: These data suggested that the selective treatment of short oesophagus in association with a Type III IV hernia reduced the anatomical recurrence rate and achieved satisfactory outcomes. CLINICALTRIALSGOV ID: NCT01606449. PMID- 26377636 TI - International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification predicts occult lymph node metastasis in clinically mediastinal node-negative lung adenocarcinoma. AB - OBJECTIVES: We investigated the role of the 2011 International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society (IASLC/ATS/ERS) classification in predicting occult lymph node metastasis in clinically mediastinal node-negative lung adenocarcinoma. METHODS: We reviewed lung adenocarcinoma patients who had clinically N2-negative status, were evaluated by preoperative positron emission tomography combined with computed tomography (PET/CT) and had undergone lobectomy or pneumonectomy at Memorial Sloan Kettering Cancer Center (n = 297). Tumours were classified according to the 2011 IASLC/ATS/ERS classification. The associations between occult lymph node metastasis and clinicopathological variables were analysed using Fisher's exact test and logistic regression analysis. RESULTS: Thirty-two (11%) cN0-1 patients had occult mediastinal lymph node metastasis (pN2) whereas 25% of cN1 patients had pN2 disease. Increased micropapillary pattern was associated with increased risk of pN2 disease (P = 0.001). On univariate analysis, high maximum standard uptake value of the primary tumour on PET/CT (P = 0.019) and the presence of micropapillary (P = 0.014) and solid pattern (P = 0.014) were associated with occult pN2 disease. On multivariable analysis, micropapillary pattern was positively associated with risk of pN2 disease (odds ratio = 3.41; 95% confidence intervals = 1.42-8.19; P = 0.006). CONCLUSIONS: The presence of micropapillary pattern is an independent predictor of occult mediastinal lymph node metastasis. Our observations have potential therapeutic implications for management of early stage lung adenocarcinoma. PMID- 26377637 TI - Long-term follow-up of total arterial revascularization with left internal thoracic artery and radial artery T-grafts: survival, cardiac morbidity and quality of life. AB - OBJECTIVES: Coronary artery bypass grafting is the gold standard for the treatment of patients with multiple-vessel coronary artery disease. The long-term outcome can be improved using arterial grafts. We analysed the initial series of patients who underwent total arterial revascularization at our institute using left internal thoracic artery (LITA) and radial artery (RA) composite T-grafts and had a follow-up of >10 years. METHODS: We included all patients who received an isolated, non-emergent total arterial revascularization using LITA-RA T-grafts between September 1996 and August 2001 in our institution. We performed a follow up of 138 patients (104 male, 60 +/- 9 years old). RESULTS: Early outcome was excellent. The 30-day mortality, reoperation, neurological complication and myocardial ischaemia rate was 1% (n = 2), 5% (n = 7), 2% (n = 3) and 2% (n = 3), respectively. Mean follow-up was 11 +/- 3 years. Long-term survival was 79% (n = 86). There were seven cardiac deaths during follow-up. Freedom from major cardiovascular events for 1, 5 and 10 years was 97, 91 and 84%, respectively. A total of 95 coronary angiographies were performed 4.6 +/- 4.1 years postoperatively. In total, 453 anastomoses using the composite graft (LITA-RA as T-graft) were performed. During follow-up, 35 anastomoses were occluded (30 RA anastomoses and 5 LITA anastomoses), leading to an occlusion rate of 7.7% during follow-up. Percutaneous coronary intervention was performed in 18 cases and coronary reoperation in two cases during follow-up. Quality-of-life assessment by Minnesota Living with Heart Failure Questionnaire revealed excellent results. CONCLUSIONS: Total arterial revascularization using composite LITA-RA T-grafts leads to excellent long-term results after >10 years. PMID- 26377638 TI - Acute myocardial infarction complicated by cardiogenic shock: results of primary percutaneous coronary interventions are insufficient. PMID- 26377639 TI - Reply to Spiliopoulos et al. PMID- 26377640 TI - A 'through-and-through bowing technique' for antegrade thoracic endovascular aneurysm repair with total arch debranching: a technical note and the initial results. AB - OBJECTIVES: The aim of this study was to evaluate the deployment accuracy of a new 'through-and-through bowing technique' that involves the deployment of the stent graft with total arch debranching via median sternotomy. METHODS: The migration distance, patients' demographic characteristics, operative values and the postoperative complications were examined retrospectively. From November 2012 to February 2013, 5 patients with an aortic arch aneurysm underwent total debranching and antegrade thoracic endovascular aneurysm repair (TEVAR) (control group). Fifteen patients underwent placement using the 'through-and-through bowing technique' (bowing group) from March to November 2013. The device was deployed as follows. A stiff guide wire was passed through the debranching prosthesis via the femoral artery. By pushing the bilateral ends of the wire against the aortic arch, the device was located along the greater curvature and bent like a bow. The migration distance, defined as the distance between the pre- and post-deployment positions of the distal end of the stent graft, was measured using fluoroscopic images. RESULTS: There were no significant differences with respect to the patients' demographics or the operative variables between the two groups. The mean migration distance in the control group (9.4 +/- 8.7 mm) was significantly longer than that in the bowing group (1.3 +/- 1.5 mm). Although one major stroke occurred in the bowing group, there was no operative mortality in either group. CONCLUSIONS: The present paper demonstrated the precise positioning of a GORE TAG deployment using a 'through-and-through bowing technique' with total arch debranching. PMID- 26377641 TI - Selection of alkalotolerant and symbiotically efficient chickpea nodulating rhizobia from North-West Indo Gangetic Plains. AB - In an effort to obtain reliable, alkali-tolerant, and symbiotically efficient rhizobial strains, 54 indigenous rhizobial isolates were obtained from root nodules of chickpea grown in alkaline soil of 5 different agricultural locations in North-West Indo Gangetic Plains (NW-IGP). Of these, 16 most symbiotically effective isolates were selected for polyphasic analysis (pH stress, salt tolerance, and genetic characterization). All the selected isolates were able to tolerate the high alkaline pH. Among them, CPN1, CPN8, and CPN32 grew well at pH 11.0. High pH-induced proteins were explored by SDS-PAGE assay. Identification and genetic characterization of isolates was done by 16S rRNA gene sequencing, RNA polymerase subunit-B (rpoB) and symbiotic genes (nodC and nifH). The study revealed diverse symbiotically efficient alkalotolerant chickpea nodulating rhizobial strains from NW-IGP. This study has thus contributed a valuable genetic pool of isolates that can potentially be used to increase chickpea production in these soil types. PMID- 26377643 TI - Isoniazid-induced hepatotoxicity in children with latent tuberculosis infection. AB - OBJECTIVES: We aimed to determine overall incidence of severe and mild isoniazid (INH) hepatotoxicity and outcome of hepatotoxicity in children who were receiving INH for latent tuberculosis. METHODS: Patients who had received isoniazid for treatment of latent tuberculosis were included in the study. Hepatotoxicity was classified according to the World Health Organization Toxicity Classification Standards. RESULTS: Among 1038 patients, overall hepatotoxicity was observed in 23 patients (2.2 %), while 5 patients (0.48 %) had moderate - severe hepatotoxicity; while other 18 patients had grade I - II hepatotoxicity (1.73%). Age and gender did not appear to be risk factors for hepatotoxicity. The median time for therapy rechallenge in patients with grade III - IV hepatotoxicity was 21 days (ranging from 14 to 25 days). CONCLUSIONS: Isoniazid hepatotoxicity is lower and generally reversible after cessation of INH in children. The grade of hepatotoxicity affects the duration for recovery of hepatotoxicity and restarting of INH therapy. PMID- 26377642 TI - Growth evaluation in children with vesicoureteral reflux. AB - BACKGROUND: Vesicoureteral reflux and urinary tract infection predispose children to retardation of growth, hypertension, renal scarring and renal failure. The aim of this study was to evaluate growth pattern in children with vesicoureteral reflux before and after medical/surgical treatment. METHODS: This study was a retrospective cross-sectional study. The study population included 97 children aged 0.5 to 17 years (8.8+/-5.5). Body weight, height and bone age of the children were measured. Weight Z score and height Z score were calculated during first visits and after medical and/or surgical treatment. Distribution, mean and standard deviation score were evaluated for the descriptive data. T-test and Mann Whitney U test and Wilcoxon test were used for statistical analysis. RESULTS: Sixty-five percent of 97 children enrolled in this study were girls. About 48.5% of the children had unilateral and mild reflux, while 16.5% had bilateral and severe reflux. The bone age was 8.6 years. Differentiation with chronological age and bone age were not significant (P=0.294). At admission, 54.6% and 50.5% of children had negative Weight Z score and height Z score, respectively. After medical and surgical treatment, Weight Z score and height Z score were increased, however, only the increase in Weight Z score was significant (P=0.039, P=0.031, respectively). A significant reduction in bone age was found in children with renal scars compared to those without renal scars (P=0.048). CONCLUSIONS: High grade vesicoureteral reflux had a negative impact on indices of growth in children. Medical and/or surgical treatment had positive effect on weight gain. PMID- 26377644 TI - Self-perception of children with autism spectrum disorders. AB - BACKGROUND: We aimed to evaluate self-perceived competence and self-esteem of primary school children with autism spectrum disorder (ASD) in Japan and compare to those of children with other chronic physical diseases and healthy controls. METHODS: Data were collected from 227 children: ASD (N.=91), nephrotic syndrome (NS) (N.=52) and asthma (N.=84), using Children's Perceived Competence Scale (CPCS) in 2012-2014. CPCS measures perceived competence in cognitive, social and physical domains, and a general self-worth domain as self-esteem. RESULTS: Scores in the social domain of the ASD group were lower than those of all other groups after adjusting for school age grades and gender. Scores of the ASD group negatively correlated with psychosomatic symptoms in all domains and IQ in the physical domain. CONCLUSIONS: These findings are the first data set in Japan on self-perceived competence and self-esteem in primary school children with ASD. Those results were comparable to previous researches in adolescents with ASD. Low social domain scores in the ASD group indicate the CPCS may be one of the useful tools to evaluate difficulty in social competence from the children's point of view. Correlations between CPCS scores and psychosomatic symptoms in the ASD group suggest development of psychosomatic symptoms may be addressed early by attention to low scores, especially in general self-worth. PMID- 26377646 TI - Atrazine-Mediated Disruption of Steroidogenesis in BLTK1 Murine Leydig Cells. AB - Atrazine (ATR) is a broad-spectrum triazine herbicide that disrupts steroidogenesis resulting in reproductive and developmental toxicity at high doses. Mouse BLTK1 Leydig cells were used as a steroidogenic model to investigate the effects of ATR on testosterone (T) biosynthesis. Induction of steroidogenesis by 3 ng/ml recombinant human chorionic gonadotropin (rhCG) induced intracellular 3',5' cyclic adenosine monophosphate (cAMP) approximately 20-fold and T approximately 3-fold at 4 h. Co-treatment with 300 MUM ATR super-induced cAMP levels 100-fold yet antagonized rhCG-mediated induction of T approximately 20% at 4 h. ATR inhibited cAMP-specific phosphodiesterase (cPDE) with an IC50 of >=98 MUM, suggesting cPDE inhibition contributes to the super-induction of cAMP. However, concentrations of up to 3 mM db-cAMP did not antagonize rhCG induction of T levels, suggesting cAMP super-induction alone does not decrease T biosynthesis. Western analysis of cAMP-activated protein kinase A (PKA) target proteins identified ATR-mediated concentration-dependent alterations in phosphorylation including phospho-CREB. These results suggest the cPDE inhibition by ATR and super-induction of cAMP are independent of effects on T levels, and that altered phosphorylation of key steroidogenic regulatory proteins may underlie ATR-mediated disruption of steroidogenesis. PMID- 26377645 TI - The AhR and NF-kappaB/Rel Proteins Mediate the Inhibitory Effect of 2,3,7,8 Tetrachlorodibenzo-p-Dioxin on the 3' Immunoglobulin Heavy Chain Regulatory Region. AB - Transcriptional regulation of the murine immunoglobulin (Ig) heavy chain gene (Igh) involves several regulatory elements including the 3'Igh regulatory region (3'IghRR), which is composed of at least 4 enhancers (hs3A, hs1.2, hs3B, and hs4). The hs1.2 and hs4 enhancers exhibit the greatest transcriptional activity and contain binding sites for several transcription factors including nuclear factor kappaB/Rel (NF-kappaB/Rel) proteins and the aryl hydrocarbon receptor (AhR). Interestingly, the environmental immunosuppressant 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD), which potently inhibits antibody secretion, also profoundly inhibits 3'IghRR and hs1.2 enhancer activation induced by the B lymphocyte activator lipopolysaccharide (LPS), but enhances LPS-induced activation of the hs4 enhancer. Within the hs1.2 and hs4 enhancers, the AhR binding site is in close proximity or overlaps an NF-kappaB/Rel binding site suggesting a potential reciprocal modulation of the 3'IghRR by AhR and NF kappaB/Rel. The objective of the current study was to evaluate the role of NF kappaB/Rel and the AhR on the 3'IghRR and its enhancers using the AhR ligand TCDD, the AhR antagonist CH223191, and toll-like receptor agonists LPS, Resiquimod (R848), or cytosine-phosphate-guanine-oligodeoxynucleotides (CpG). Utilizing the CH12.LX B-lymphocyte cell line and variants expressing either a 3'IghRR-regulated transgene reporter or an inducible IkappaBalpha (inhibitor kappa B-alpha protein) superrepressor (IkappaBalphaAA), we demonstrate an AhR- and NF-kappaB/Rel-dependent modulation of 3'IghRR and hs4 activity. Additionally, in mouse splenocytes or CH12.LX cells, binding within the hs1.2 and hs4 enhancer of the AhR and the NF-kappaB/Rel proteins RelA and RelB was differentially altered by the cotreatment of LPS and TCDD. These results suggest that the AhR and NF-kappaB/Rel protein binding profile within the 3'IghRR mediates the inhibitory effects of TCDD on Ig expression and therefore antibody levels. PMID- 26377647 TI - 2,3,7,8-Tetrachlorodibenzo-p-Dioxin Alters Lipid Metabolism and Depletes Immune Cell Populations in the Jejunum of C57BL/6 Mice. AB - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent aryl hydrocarbon receptor agonist that elicits dose-dependent hepatic fat accumulation and inflammation that can progress to steatohepatitis. To investigate intestine-liver interactions that contribute to TCDD-elicited steatohepatitis, we examined the dose-dependent effects of TCDD (0.01, 0.03, 0.1, 0.3, 1, 3, 10, or 30 ug/kg) on jejunal epithelial gene expression in C57BL/6 mice orally gavaged every 4 days for 28 days. Agilent 4x44K whole-genome microarray analysis of the jejunal epithelium identified 439 differentially expressed genes (|fold change| >= 1.5, P1(t) >= 0.999) across 1 or more doses, many related to lipid metabolism and immune system processes. TCDD-elicited differentially expressed genes were associated with lipolysis, fatty acid/cholesterol absorption and transport, the Kennedy pathway, and retinol metabolism, consistent with increased hepatic fat accumulation. Moreover, several major histocompatibility complex (MHC) class II genes (H2-Aa, H2-Ab1, H2-DMb1, Cd74) were repressed, coincident with decreased macrophage and dendritic cell levels in the lamina propria, suggesting migration of antigen presenting cells out of the intestine. In contrast, hepatic RNA-Seq analysis identified increased expression of MHC class II genes, as well as chemokines and chemokine receptors involved in macrophage recruitment (Ccr1, Ccr5, Ccl5, Cx3cr1), consistent with hepatic F4/80 labeling and macrophage infiltration into the liver. Collectively, these results suggest TCDD elicits changes that support hepatic lipid accumulation, macrophage migration, and the progression of hepatic steatosis to steatohepatitis. PMID- 26377649 TI - Novel Therapeutic Strategies for Cardiovascular Disease Treatment: From Molecular Level to Nanotechnology. PMID- 26377650 TI - Regulation of GABA Neurotransmission by Glutamic Acid Decarboxylase (GAD). AB - Control of GABA neurotransmission at the pre-synaptic site occurs substantially through the activation of the glutamic acid decarboxylase (GAD) enzymes GAD65 and GAD67. Concentrations of GAD65 and GAD67 are controlled either by transcription or by mRNA splicing and importantly the activities of these key enzymes are regulated by post-translational mechanisms. Important post-translational modifications include proteolytic cleavage, phosphorylation and palmitoylation. A truncated form of GAD65 (tGAD65) is more active than full length GAD65 (fGAD65) whereas, by contrast, truncated GAD67 (tGAD67) is less active than full length GAD67 (fGAD67). The protein responsible for cleaving of fGAD65 and fGAD67 is mu calpain. GABA neurotransmission is dependent upon whether GAD is associated with synaptic vesicles (SV) and calpain performs a vital role by generating the highly active tGAD65 resulting in augmented GABA synthesis and wrapping uptake into SV. Studies on GAD phosphorylation demonstrate that GAD65 is regulated through phosphorylation by PKC while GAD67 is inhibited through phosphorylation by PKA. Cysteine residues 455 and 446 in GAD67 and GAD65 individually are critical for full GAD regulation. Interaction with the cofactor pyridoxal 50-phosphate (PLP) at this these respective locations regulate the switch between PLP-bound active holoGAD and an unbound active apoGAD form. Transient switching to the PLP bound active holoGAD is integral to GABA neurotransmission. Specific to GAD65 but not GAD67 is palmitoylation by HIP14 which facilitates GAD65 anchoring to SV and enhances the contribution of vesicular GABA to neurotransmission. From studies on a rodent stroke model calpain-mediated cleavage of GAD enzyme has been shown to occur under pathological conditions resulting in less SV refilling and depletion of existing pools of SV releasable GABA. PMID- 26377651 TI - Nano-Systems for Advanced Therapeutics and Diagnosis of Atherosclerosis. AB - Cardiovascular diseases (CVDs) are the leading cause of death and morbidity worldwide. Atherosclerotic situations such as acute myocardial infarction(MI) and stroke are still major causes of death worldwide. Present therapeutic approaches based on conventional drug delivery systems are not efficient to control these disorders. With the technological advancement and intervention of nanotechnology, several fascinating areas are explored for the management of these disorders. Targeted drug delivery approaches and diagnostic tools presented by nanotechnology, certainly took the atherosclerotic disease management to next level. Criticality lies in the rationale selection of an appropriately designed nanocarrier for targeting a specific zone of disease. Manuscript provides a descriptive view of disease targets; nanotechnology based therapeutic and diagnostic approaches and different nanocarriers to accomplish this task. It is important to have the understanding of different classes of these nanosystems along with their specific merits and demerits. Mechanisms and approaches for improving the selectivity or targeting potential are also discussed. There is no doubt that nanotechnology is having great impact in this area, but it is equally important to rationalize its scale up aspects for a real world success. PMID- 26377648 TI - Type 2 immunity-dependent reduction of segmented filamentous bacteria in mice infected with the helminthic parasite Nippostrongylus brasiliensis. AB - BACKGROUND: Dynamic interactions between the host and gastrointestinal microbiota play an important role for local and systemic immune homeostasis. Helminthic parasites modulate the host immune response, resulting in protection against autoimmune disease but also increased susceptibility to pathogen infection. The underlying mechanisms remain largely unknown. RESULTS: We showed that the type 2 immune response to enteric Nippostrongylus brasiliensis infection in mice was associated with altered intestinal mucin and AMP expression and shifts in microbiota composition. Most strikingly, infection reduced concentrations of intestinal segmented filamentous bacteria (SFB), known inducers of T helper 17 cells, and IL-17-associated gene expression. Infected mice deficient in IL-13 or STAT6 did not reduce SFB or IL-17, and exogenous IL-25 replicated the effects of parasite infection in wild type mice. CONCLUSIONS: Our data show that parasite infection acts through host type 2 immunity to reduce intestinal SFB and expression of IL-17, providing an example of a microbiota-dependent immune modulation by parasites. PMID- 26377652 TI - SYNTHESIS AND APPLICATIONS OF Fe3O4/SiO2 CORE-SHELL MATERIALS. AB - Multifunctional nanoparticles based on magnetite/silica core-shell, consisting of iron oxides coated with silica matrix doped with fluorescent components such as organic dyes (fluorescein isothiocyanate - FITC, Rhodamine 6G) or quantum dots, have drawn remarkable attention in the last years. Due to the bi-functionality of these types of nanoparticles (simultaneously having magnetic and fluorescent properties), they are successfully used in highly efficient human stem cell labeling, magnetic carrier for photodynamic therapy, drug delivery, hyperthermia and other biomedical applications. Another application of core-shell-based nanoparticles, in which the silica is functionalized with aminosilanes, is for immobilization and separation of various biological entities such as proteins, antibodies, enzymes etc. as well as in environmental applications, as adsorbents for heavy metal ions. In vitro tests on human cancerous cells, such as A549 (human lung carcinoma), breast, human cervical cancer, THP-1 (human acute monocytic leukaemia) etc. , were conducted to assess the potential cytotoxic effects that may occur upon contact of nanoparticles with cancerous tissue. Results show that core-shell nanoparticles doped with cytostatics (cisplatin, doxorubicin, etc.), are easily adsorbed by affected tissue and in some cases lead to an inhibition of cell proliferation and induce cell death by apoptosis. The goal of this review is to summarize the advances in the field of core-shell materials, particularly those based on magnetite/silica with applicability in medicine and environmental protection. This paper briefly describes synthesis methods of silica-coated magnetite nanoparticles (Stober method and microemulsion), the method of encapsulating functional groups based on aminosilanes in silica shell, as well as applications in medicine of these types of simple or modified nanoparticles for cancer therapy, MRI, biomarker immobilization, drug delivery, biocatalysis etc., and in environmental applications (removal of heavy metal ions and catalysis). PMID- 26377653 TI - MAGNETIC CORE SHELL STRUCTURES: from 0D to 1D assembling. AB - Material research and development studies are focused on different techniques of bringing out nanomaterials with desired characteristics and properties. From the point of view of materials development, nowadays scientists are strongly focused on obtaining materials with predefined characteristics and properties. The morphology control seems to be a determinant factor and increasing attention is devoted to this aspect. At this moment it is possible to engineer the material's features by using different methods and materials combination for both medical and industrial applications. In the applications of chemistry and synthesis, biology, mechanics, optics solar cells and microelectronics tailoring the adjustable parameters of stoichiometry, chemical structure, shape and segregation are evaluated and opens new fields. Because of the magnetic features of nanoparticles and durable particle size, less than 100 nm, this study is aiming to describe their uses in practical applications. That's why the whole hydrodynamic magnetic core shell topic will be reviewed on this paper. Additionally, the properties acting in general sight in solid-state physics are utilized for material selection and for defining issue connecting the core, shell structure and their producing properties. Here, in the study of core/shell nanoparticle various physical and chemical synthesis routes and the effect of electrospun method are briefly discussed. Starting from a real void of the scientific literature, the existent data related to the 1D magnetic electrospun materials are reviewed. The perspectives in the medical, environmental or energetic sector is great and bring some real advantages related to the 0D core@shell structures because both mechanical and biological properties are dependent on the morphology of the materials. PMID- 26377654 TI - Current Status of Magnetite-Based Core@Shell Structures for Diagnosis and Therapy in Oncology Short running title: Biomedical Applications of Magnetite@Shell Structures. AB - Superparamagnetic iron oxides, as magnetite (Fe3O4) or maghemite (gamma-Fe2O3), are primary materials with intrinsic properties that enable them, as single components or as special composites, to base advanced techniques in medical clinical practices, as a contrast agent in magnetic resonance imaging (MRI), as magnetically-induced hyperthermic heat generator, and as a magnetic guide to locally deliver drugs to specific sites in the human body. An interesting approach to developing nanoplatforms for those applications consists in manufacturing core@shell nanostructures, in which the precursor magnetic iron oxide (usually, magnetite) acts as a core, and an organic, or inorganic compound is used as a shell in a multifunctional composite. In this review, we report the current advances in the use of magnetite-based core@shell nanostructures, including Fe3O4@SiO2 and Fe3O4@polymers, in MRI, magnetic hyperthermia and drug delivery systems for diagnosis and therapy of tumor cells. The development of nanoplatforms for combined therapy and diagnostic (theranostic) is also addressed. PMID- 26377655 TI - Engineered Magnetic Core-Shell Structures. AB - In recent years, engineered magnetic core-shell structures are playing an important role in the wide range of various applications. These magnetic core shell structures have attracted considerable attention because of their unique properties and various applications. Also, the synthesis of engineered magnetic core-shell structures has attracted practical interest because of potential applications in areas such as ferrofluids, medical imaging, drug targeting and delivery, cancer therapy, separations, and catalysis. So far a large number of engineered magnetic core-shell structures have been successfully synthesized. This review article focuses on the recent progress in synthesis and characterization of engineered magnetic core-shell structures. Also, this review gives a brief description of the various application of these structures. It is hoped that this review will play some small part in helping future developments in important field. PMID- 26377656 TI - Opportunities and Challenges of Fluorescent Carbon Dots in Translational Optical Imaging. AB - The fluorescent carbon dot (C-dot) is a new class of carbon nanomaterials. It has a discrete or quasispherical structure, typically measures less than 10 nm and contains sp(2)/sp(3) carbon, oxygen/nitrogen-based groups and surface-modified functional groups. Compared with semiconductor quantum dots (QDs), C-dots offer much lower toxicity and a better biocompatibility profile. Their other favorable features include easy and inexpensive synthesis and surface modification potential. C-dots can be morphologically classified into graphene-based quantum dots (GQDs) and amorphous carbon nanodots (ACNDs). Numerous methods have been developed to synthesize C-dots, and are mainly divided into 'top-down' and 'bottom-up' routes. In the top-down route, C-dots (mostly GQDs) is derived from the separation of large carbon precursors. The 'bottom-up' method primarily involves the dehydration, polymerization and carbonization of small molecules to form the GQDs and ACNDs through thermal/hydrothermal synthesis, microwave irradiation, and solution chemistry. Potential applications of C-dots have been explored in a number of cellular and in-vivo imaging approaches. However, some difficulties remain, including limited penetration depth and poorly controlled in vivo pharmacokinetics, which depends on multiple factors such as the morphology, physiochemical properties, surface chemistry and formulation of C-dots. The exact mechanism of in-vivo biodistribution, cellular uptake and long-term toxicological effect of C-dots still need to be elucidated. An integrated multi-disciplinary approach involving chemists, pharmacologists, toxicologists, clinicians, and regulatory bodies at the early stage is essential to enable the clinical application of C-dots. PMID- 26377657 TI - A Survey on Synthesis Processes of Structured Materials for Biomedical Applications: Iron-based Magnetic Nanoparticles, Polymeric Materials and Polymerization Processes. AB - Magnetic materials based on iron oxides are extensively designed for several biomedical applications. Heterogeneous polymerization processes are powerful tools for the production of tailored micro-sized and nanosized magneto-polymeric particles. Although several polymerization processes have been adopted along the years, suspension, emulsion and miniemulsion systems deserve special attention due to its ability to produce spherical polymer particles containing magnetic nanoparticles homogeneously dispersed into the polymer thermoplastic matrices. The main objective of this paper is to review the main methods of synthesis of iron-based magnetic nanoparticles and to illustrate how typical polymerization processes in different dispersion medium can be successfully used to produce engineered magnetic core-shell structures. It is exemplified the use of suspension, emulsion and miniemulsion polymerization processes in order to support experimental methodologies required for the production of magnetic polymer particles intended for biomedical applications such as intravascular embolization treatments, drug delivery systems and hyperthermia treatment. PMID- 26377658 TI - Engineered Inorganic/Organic-Core/Shell Magnetic FexOy Nanoparticles with Oleic Acid and/or Oleylamine As Capping Agents. AB - Magnetic nanoparticles with tailored surface chemistry are widely used for a number of different in vivo applications, ranging from tissue repair and magnetic cell separation through to cancer-hyperthermia, drug delivery and magnetic resonance imaging contrast enhancement. A major requirement for all these biomedical applications is that these nanoparticles must have high magnetization values and sizes smaller than 100 nm with a narrow particle size distribution. Thus nanoparticles must have uniform physical and chemical properties. For these applications, a tailored surface coating/shell needs to be engineered, which has to be non-toxic, biocompatible and make allowance for targetable drug delivery with particle localization in a targeted area. Most work in this field has been done on improving the biocompatibility of the nanoparticles. Only a few scientific investigations have been carried out on improving the quality of magnetic nanoparticles with specific focus on the nanoparticle's surface chemistry, size distribution and shape (which directly influences the magnetic properties). All these particles also need to be properly characterized in order to get a protocol for the quality control of these particles, the nature of the surface coatings and their subsequent geometric arrangement. This will ultimately determine the overall size of the colloids and also plays a significant role in biokinetics and biodistribution of nanoparticles in the body. This review highlights recent advances in the synthetic chemistry, magnetic characterization and biological applications of inorganic/organic - core/shell FexOy based magnetic nanoparticles with specific focus on using the two popular surfactants for producing MNPs namely oleic acid and/or oleylamine as capping agents. Although the main nano-magnets under discussion are magnetite (Fe3O4) nanoparticles, maghemite (gamma-Fe2O3) is also briefly mentioned. PMID- 26377659 TI - Neuropilin-1 (NRP-1) and Magnetic Nanoparticles, a Potential Combination for Diagnosis and Therapy of Gliomas. AB - In this review, Neuropilin-1 (NRP-1) has been focused as a novel molecular target for potential treatment of gliomas. The properties of NRP-1 were described briefly. The role of NRP-1 in gliomas was explored in details, including relationships of NRP-1 expression and glioma prognosis, Sema3A-NRP-1 signaling in gliomas, NRP-1 signaling and VEGF/VEGFR, PlGF, TGF-beta, PDGF, LD22-4 of FGF2, autocrine of HGF/SF, p130Cas tyrosine phosphorylation and integrin-associated tumor microenvironment in gliomas, NRP-1 intracellular trafficking, NRP-1 and glioma stem-like cells, as well as magnetic nanoparticles related to targeting gliomas. NRP-1, a multifunctional-receptors protein, would mediate diverse cellular signaling pathways in gliomas, and might potentially act as a novel therapeutic target. In future, magnetic nanoparticles coated with NRP-1 may play a vital role on diagnosis and therapy of gliomas. PMID- 26377660 TI - Glucose Sensors Based on Core@Shell Magnetic Nanomaterials and Their Application in Diabetes Management: A Review. AB - This review presents a comprehensive attempt to conclude and discuss various glucose biosensors based on core@shell magnetic nanomaterials. Owing to good biocompatibility and stability, the core@shell magnetic nanomaterials have found widespread applications in many fields and draw extensive attention. Most magnetic nanoparticles possess an intrinsic enzyme mimetic activity like natural peroxidases, which invests magnetic nanomaterials with great potential in the construction of glucose sensors. We summarize the synthesis of core@shell magnetic nanomaterials, fundamental theory of glucose sensor and the advances in glucose sensors based on core@shell magnetic nanomaterials. The aim of the review is to provide an overview of the exploitation of the core@shell magnetic nanomaterials for glucose sensors construction. PMID- 26377661 TI - Quantitative Characterization of Magnetic Mobility of Nanoparticle in Solution Based Condition. AB - Magnetic nanoparticles are considered as the ideal substrate to selectively isolate target molecules or organisms from sample solutions in a wide variety of applications including bioassays, bioimaging and environmental chemistry. The broad array of these applications in fields requires the accurate magnetic characterization of nanoparticles for a variety of solution based-conditions. Because the freshly synthesized magnetic nanoparticles demonstrated a perfect magnetization value in solid form, they exhibited a different magnetic behavior in solution. Here, we present simple quantitative method for the measurement of magnetic mobility of nanoparticles in solution-based condition. Magnetic mobility of the nanoparticles was quantified with initial mobility of the particles using UV-vis absorbance spectroscopy in water, ethanol and MES buffer. We demonstrated the efficacy of this method through a systematic characterization of four different core-shell structures magnetic nanoparticles over three different surface modifications. The solid nanoparticles were characterized using transmission electron microscopy (TEM), X-ray diffraction (XRD) and saturation magnetization (Ms). The surfaces of the nanoparticles were functionalized with 11 mercaptoundecanoic acid and bovine serum albumin BSA was selected as biomaterial. The effect of the surface modification and solution media on the stability of the nanoparticles was monitored by zeta potentials and hydrodynamic diameters of the nanoparticles. Results obtained from the mobility experiments indicate that the initial mobility was altered with solution media, surface functionalization, size and shape of the magnetic nanoparticle. The proposed method easily determines the interactions between the magnetic nanoparticles and their surrounding biological media, the magnetophoretic responsiveness of nanoparticles and the initial mobilities of the nanoparticles. PMID- 26377663 TI - Reliability analysis of Cobb angle measurements of congenital scoliosis using X ray and 3D-CT images. AB - PURPOSE: Therapeutic decisions for congenital scoliosis rely on Cobb angle measurements on consecutive radiographs. There have been no studies documenting the variability of measuring the Cobb angle using 3D-CT images in children with congenital scoliosis. The purpose of this study was to compare the reliability and measurement errors using X-ray images and those utilizing 3D-CT images. MATERIALS AND METHODS: The X-ray and 3D-CT images of 20 patients diagnosed with congenital scoliosis were used to assess the reliability of the digital 3D-CT images for the measurement of the Cobb angle. Thirteen observers performed the measurements, and each image was analyzed by each observer twice with a minimum interval of 1 week between measurements. The analysis of intraobserver variation was expressed as the mean absolute difference (MAD) and standard deviation (SD) between measurements and the intraclass correlation coefficient (IaCC) of the measurements. In addition, the interobserver variation was expressed as the MAD and interclass correlation coefficient (IeCC). RESULTS: The average MAD and SD was 4.5 degrees and 3.2 degrees by the X-ray method and 3.7 degrees and 2.6 degrees by the 3D-CT method. The intraobserver and interobserver intraclass ICCs were excellent in both methods (X-ray: IaCC 0.835-0.994 IeCC 0.847, 3D-CT: IaCC 0.819-0.996 IeCC 0.893). There was no significant MAD difference between X-ray and 3D-CT images in measuring each type of congenital scoliosis by each observer. CONCLUSIONS: Results of Cobb angle measurements in patients with congenital scoliosis using X-ray images in the frontal plane could be reproduced with almost the same measurement variance (3 degrees -4 degrees measurement error) using 3D CT images. This suggests that X-ray images are clinically useful for assessing any type of congenital scoliosis about measuring the Cobb angle alone. However, since 3D-CT can provide more detailed images of the anterior and posterior components of malformed vertebrae, the volume of information that can be obtained by evaluating them has contributed greatly to the development of strategies for the surgical treatment of congenital scoliosis. PMID- 26377662 TI - ASA III osteoporotic fracture in 62 patients treated with vertebroplasty under local anesthesia. AB - Vertebroplasty is a minimally invasive procedure that may be performed under either local or general anesthesia. In this study, we aimed at assessing the outcomes of the vertebroplasty performed under local anesthesia in patients at high risk of general anesthesia. Vertebroplasty was performed under local anesthesia in the treatment of a total of 62 patients (68 vertebrae in total) with osteoporotic vertebral fractures between 2011 and 2013. None of the patients had a history of trauma. Patients who were classified as ASA III during the preoperative examinations were included in the study. VAS scores were evaluated before the surgery, on the first postoperative day, and in week 1 and in month 1 after the surgery. The average age was 77.5 years (age range 53-102). An average of 2 cc of cement was injected to 22 patients (35.5 %), and an average of 3 cc of cement was injected to 40 patients (64.5 %). The mean VAS scores were 7.52 (6-9) before the procedure, 3.55 (2-5) on the first day, 2.03 (0-4) in week 1 and 0.87 (0-2) in month 1 postoperatively. Asymptomatic cement embolism was detected in one patient. No other complications were observed in the study group. Vertebroplasty performed under local anesthesia is an effective and safe procedure in terms of pain control and early ambulation and is bereft of the complications associated with general anesthesia. PMID- 26377664 TI - Prostaglandin E2 and the EP receptors in malignancy: possible therapeutic targets? AB - Elevated expression of COX-2 and increased levels of PGE2 are found in numerous cancers and are associated with tumour development and progression. Although epidemiological, clinical and preclinical studies have shown that the inhibition of PGE2 synthesis through the use of either non-steroidal anti-inflammatory drugs (NSAIDs) or specific COX-2 inhibitors (COXibs) has the potential to prevent and treat malignant disease, toxicities due to inhibition of COX-2 have limited their use. Thus, there is an urgent need for the development of strategies whereby COX 2 activity may be reduced without inducing any side effects. The biological effects of PGE2 are mediated by signalling through four distinct E-type prostanoid (EP) receptors - EP1 , EP2 , EP3 and EP4 . In recent years, extensive effort has gone into elucidating the function of PGE2 and the EP receptors in health and disease, with the goal of creating selective inhibitors as a means of therapy. In this review, we focus on PGE2 , and in particular on the role of the individual EP receptors and their signalling pathways in neoplastic disease. As knowledge concerning the role of the EP receptors in cancer grows, so does the potential for exploiting the EP receptors as therapeutic targets for the treatment of cancer and metastatic disease. PMID- 26377665 TI - Comforting strategies and perceived barriers to pediatric pain management during IV line insertion procedure in Uganda's national referral hospital: A descriptive study. AB - BACKGROUND: Venipuncture and intravenous (IV) cannula insertions are the two common sources of pain in hospitalized children and health care today. The WHO asserts that, pain relief is a basic fundamental right and requires a multidisciplinary approach. Nonpharmacological comforting strategies when implemented are important to relive pain related distress in children during peripheral IV line insertion. However, evidence to date that suggests implementation of such strategies and their barriers in Uganda remains very limited. This study aimed at establishing the current practices in regard to the use of comforting strategies and the perceived barriers faced by health care providers to implement pediatric pain management during IV line insertion procedure in Uganda's national referral hospital, Mulago. METHOD: A cross sectional and descriptive study was conducted between December 1, 2012 and February 28, 2013 involving doctors, nurses and interns in six pediatric wards of Mulago Hospital in Uganda. A pre-tested self- administered and semi- structured questionnaire was used to collect the data. Data was entered into SPSS and descriptive statistics run on all the variables. RESULTS: Of the 120 questionnaires distributed, 105 (RR = 87.5%) were returned and completed. The evidence based comforting strategies used for pain management during IV line insertion by the majority of health care professionals were; skin to skin (51%) and appropriate upright positioning of the child on mother's lap (69%). The least used comforting strategies were; allowing the child to suck his thumb or hand (70%), use of distraction (69%) and directing the child to suck one of his fingers into his mouth (90%). The identified barriers to implementing comforting strategies were; lack of time (42%), having emergency situations (18%), and not knowing the right method to use (11%). Of 105, 100 (95%) reported that there is need for continuous professional development on comforting strategies. CONCLUSIONS: Findings demonstrated that fewer health care providers used some evidence based comforting strategies of pain relief during pediatric peripheral IV line insertion. Distraction and other evidence based strategies for pain and distress relieve are less often used by the majority of the health care providers. Incorporating pediatric pain management content in all health professionals training curricula could improve the current practices for better health outcomes. PMID- 26377666 TI - An intact helical domain is required for Galpha14 to stimulate phospholipase Cbeta. AB - BACKGROUND: Stimulation of phospholipase Cbeta (PLCbeta) by the activated alpha subunit of Gq (Galphaq) constitutes a major signaling pathway for cellular regulation, and structural studies have recently revealed the molecular interactions between PLCbeta and Galphaq. Yet, most of the PLCbeta-interacting residues identified on Galphaq are not unique to members of the Galphaq family. Molecular modeling predicts that the core PLCbeta-interacting residues located on the switch regions of Galphaq are similarly positioned in Galphaz which does not stimulate PLCbeta. Using wild-type and constitutively active chimeras constructed between Galphaz and Galpha14, a member of the Galphaq family, we examined if the PLCbeta-interacting residues identified in Galphaq are indeed essential. RESULTS: Four chimeras with the core PLCbeta-interacting residues composed of Galphaz sequences were capable of binding PLCbeta2 and stimulating the formation of inositol trisphosphate. Surprisingly, all chimeras with a Galphaz N-terminal half failed to functionally associate with PLCbeta2, despite the fact that many of them contained the core PLCbeta-interacting residues from Galpha14. Further analyses revealed that the non-PLCbeta2 interacting chimeras were capable of interacting with other effector molecules such as adenylyl cyclase and tetratricopeptide repeat 1, indicating that they could adopt a GTP-bound active conformation. CONCLUSION: Collectively, our study suggests that the previously identified PLCbeta-interacting residues are insufficient to ensure productive interaction of Galpha14 with PLCbeta, while an intact N-terminal half of Galpha14 is apparently required for PLCbeta interaction. PMID- 26377667 TI - Effects of population structure on pollen flow, clonality rates and reproductive success in fragmented Serapias lingua populations. AB - BACKGROUND: Fragmentation of habitats by roads, railroads, fields, buildings and other human activities can affect population size, pollination success, sexual and asexual reproduction specially in plants showing pollinator limitation, such as Mediterranean orchids. In this study, we assessed pollen flow, selfing rates, vegetative reproduction and female reproductive success and their correlations with habitat characters in nine fragmented subpopulations of Serapias lingua. To improve understanding of population structure effects on plant biology, we examined genetic differentiation among populations, pollen flow, selfing rates and clonal reproduction using nuclear microsatellite markers. RESULTS: Smaller populations showed a significant heterozygote deficit occurred at all five nuclear microsatellite loci, the coefficient of genetic differentiation among populations was 0.053 and pairwise FST was significantly correlated with the geographical distance between populations. Paternity analysis of seeds showed that most pollen flow occurred within a population and there was a positive correlation between percentage of received pollen and distance between populations. The fruit production rate varied between 5.10 % and 20.30 % and increased with increasing population size, while the percentage of viable seeds (78-85 %) did not differ significantly among populations. The extent of clonality together with the clonal and sexual reproductive strategies varied greatly among the nine populations and correlated with the habitats where they occur. The small, isolated populations tended to have high clonal diversity and low fruit production, whereas the large populations with little disturbance were prone to have reductions in clonal growth and increased sexual reproduction. CONCLUSIONS: We found that clonality offers an advantage in small and isolated populations of S. lingua, where clones may have a greater ability to persist than sexually reproducing individuals. PMID- 26377668 TI - Autonomy-Supportive Parenting and Autonomy-Supportive Sibling Interactions: The Role of Mothers' and Siblings' Psychological Need Satisfaction. AB - Autonomy-supportive parenting yields manifold benefits. To gain more insight into the family-level dynamics involved in autonomy-supportive parenting, the present study addressed three issues. First, on the basis of self-determination theory, we examined whether mothers' satisfaction of the psychological needs for autonomy, competence, and relatedness related to autonomy-supportive parenting. Second, we investigated maternal autonomy support as an intervening variable in the mother-child similarity in psychological need satisfaction. Third, we examined associations between autonomy-supportive parenting and autonomy supportive sibling interactions. Participants were 154 mothers (M age = 39.45, SD = 3.96) and their two elementary school-age children (M age = 8.54, SD = 0.89 and M age = 10.38, SD = 0.87). Although mothers' psychological need satisfaction related only to maternal autonomy support in the younger siblings, autonomy supportive parenting related to psychological need satisfaction in both siblings and to an autonomy-supportive interaction style between siblings. We discuss the importance of maternal autonomy support for family-level dynamics. PMID- 26377669 TI - The balanced ideological antipathy model: explaining the effects of ideological attitudes on inter-group antipathy across the political spectrum. AB - We introduce the balanced ideological antipathy (BIA) model, which challenges assumptions that right-wing authoritarianism (RWA) and social dominance orientation (SDO) predict inter-group antipathy per se. Rather, the effects of RWA and SDO on antipathy should depend on the target's political orientation and political objectives, the specific components of RWA, and the type of antipathy expressed. Consistent with the model, two studies (N = 585) showed that the Traditionalism component of RWA positively and negatively predicted both political intolerance and prejudice toward tradition-threatening and -reaffirming groups, respectively, whereas SDO positively and negatively predicted prejudice (and to some extent political intolerance) toward hierarchy-attenuating and enhancing groups, respectively. Critically, the Conservatism component of RWA positively predicted political intolerance (but not prejudice) toward each type of target group, suggesting it captures the anti-democratic impulse at the heart of authoritarianism. Recommendations for future research on the relationship between ideological attitudes and inter-group antipathy are discussed. PMID- 26377671 TI - Spinal Cord Blood Supply and Its Surgical Implications. AB - The blood supply to the spine is based on a predictable segmental vascular structure at each spinal level, but true radiculomedullary arteries, which feed the dominant cord supply vessel, the anterior spinal artery, are relatively few and their locations variable. Under pathologic conditions, such as aortic stent grafting, spinal deformity surgery, or spinal tumor resection, sacrifice of a dominant radiculomedullary vessel may or may not lead to spinal cord ischemia, depending on dynamic autoregulatory or collateral mechanisms to compensate for its loss. Elucidation of the exact mechanisms for this compensation requires further study but will be aided by preoperative, intraoperative, and postoperative comparative angiography. Protocols in place at our center and others minimize the risk of spinal cord ischemia during planned radiculomedullary vessel sacrifice. PMID- 26377670 TI - Lack of neuroinflammation in the HIV-1 transgenic rat: an [(18)F]-DPA714 PET imaging study. AB - BACKGROUND: HIV-associated neuroinflammation is believed to be a major contributing factor in the development of HIV-associated neurocognitive disorders (HAND). In this study, we used micropositron emission tomography (PET) imaging to quantify neuroinflammation in HIV-1 transgenic rat (Tg), a small animal model of HIV, known to develop neurological and behavioral problems. METHODS: Dynamic [(18)F]DPA-714 PET imaging was performed in Tg and age-matched wild-type (WT) rats in three age groups: 3-, 9-, and 16-month-old animals. As a positive control for neuroinflammation, we performed unilateral intrastriatal injection of quinolinic acid (QA) in a separate group of WT rats. To confirm our findings, we performed multiplex immunofluorescent staining for Iba1 and we measured cytokine/chemokine levels in brain lysates of Tg and WT rats at different ages. RESULTS: [(18)F]DPA-714 uptake in HIV-1 Tg rat brains was generally higher than in age-matched WT rats but this was not statistically significant in any age group. [(18)F]DPA-714 uptake in the QA-lesioned rats was significantly higher ipsilateral to the lesion compared to contralateral side indicating neuroinflammatory changes. Iba1 immunofluorescence showed no significant differences in microglial activation between the Tg and WT rats, while the QA lesioned rats showed significant activation. Finally, cytokine/chemokine levels in brain lysates of the Tg rats and WT rats were not significantly different. CONCLUSION: Microglial activation might not be the primary mechanism for neuropathology in the HIV-1 Tg rats. Although [(18)F]DPA-714 is a good biomarker of neuroinflammation, it cannot be reliably used as an in vivo biomarker of neurodegeneration in the HIV-1 Tg rat. PMID- 26377672 TI - AAOS Appropriate Use Criteria: Management of Pediatric Supracondylar Humerus Fractures. PMID- 26377673 TI - Clinical Evaluation and Preoperative Planning of Articular Cartilage Lesions of the Knee. AB - Articular cartilage injuries are quite common. Most studies and review articles on cartilage repair and restoration focus on the different techniques available to treat cartilage defects; however, few thoroughly discuss the initial evaluation of patients with these defects. Outcomes are intimately associated with appropriate patient selection and indications for treatment; therefore, understanding the initial evaluation and conservative treatment of cartilage defects is essential to achieving excellent outcomes after surgical intervention, regardless of the chosen procedure. In patients with cartilage injury, a careful history, physical examination, and imaging are required before treating the lesion to ensure the patient's symptoms are actually related to the defect. To address any special considerations, other factors must be considered to improve patient outcomes, including the status of the meniscus, assessing and treating malalignment or off-loading the patellofemoral compartment, and reconstructing any ligamentous deficiencies. It is important for medical providers to understand what cartilage lesions may be symptomatic and when to refer these patients to surgeons who manage cartilage injury. PMID- 26377674 TI - Impact of physical activity, sedentary behaviour and muscle strength on bone stiffness in 2-10-year-old children-cross-sectional results from the IDEFICS study. AB - BACKGROUND: Physical activity (PA), weight-bearing exercises (WBE) and muscle strength contribute to skeletal development, while sedentary behaviour (SB) adversely affects bone health. Previous studies examined the isolated effect of PA, SB or muscle strength on bone health, which was usually assessed by x-ray methods, in children. Little is known about the combined effects of these factors on bone stiffness (SI) assessed by quantitative ultrasound. We investigated the joint association of PA, SB and muscle strength on SI in children. METHODS: In 1512 preschool (2- < 6 years) and 2953 school children (6-10 years), data on calcaneal SI as well as on accelerometer-based sedentary time (SED), light (LPA), moderate (MPA) and vigorous PA (VPA) were available. Parents reported sports (WBE versus no WBE), leisure time PA and screen time of their children. Jumping distance and handgrip strength served as indicators for muscle strength. The association of PA, SB and muscle strength with SI was estimated by multivariate linear regression, stratified by age group. Models were adjusted for age, sex, country, fat-free mass, daylight duration, consumption of dairy products and PA, or respectively SB. RESULTS: Mean SI was similar in preschool (79.5 +/- 15.0) and school children (81.3 +/- 12.1). In both age groups, an additional 10 min/day in MPA or VPA increased the SI on average by 1 or 2%, respectively (p <= .05). The negative association of SED with SI decreased after controlling for MVPA. LPA was not associated with SI. Furthermore, participation in WBE led to a 3 and 2% higher SI in preschool (p = 0.003) and school children (p < .001), respectively. Although muscle strength significantly contributed to SI, it did not affect the associations of PA with SI. In contrast to objectively assessed PA, reported leisure time PA and screen time showed no remarkable association with SI. CONCLUSION: This study suggests that already an additional 10 min/day of MPA or VPA or the participation in WBE may result in a relevant increase in SI in children, taking muscle strength and SB into account. Our results support the importance of assessing accelerometer-based PA in large-scale studies. This may be important when deriving dose-response relationships between PA and bone health in children. PMID- 26377675 TI - Incorporating Psychological Predictors of Treatment Response into Health Economic Simulation Models: A Case Study in Type 1 Diabetes. AB - BACKGROUND: . Health economic modeling has paid limited attention to the effects that patients' psychological characteristics have on the effectiveness of treatments. This case study tests 1) the feasibility of incorporating psychological prediction models of treatment response within an economic model of type 1 diabetes, 2) the potential value of providing treatment to a subgroup of patients, and 3) the cost-effectiveness of providing treatment to a subgroup of responders defined using 5 different algorithms. METHODS: . Multiple linear regressions were used to investigate relationships between patients' psychological characteristics and treatment effectiveness. Two psychological prediction models were integrated with a patient-level simulation model of type 1 diabetes. Expected value of individualized care analysis was undertaken. Five different algorithms were used to provide treatment to a subgroup of predicted responders. A cost-effectiveness analysis compared using the algorithms to providing treatment to all patients. RESULTS: . The psychological prediction models had low predictive power for treatment effectiveness. Expected value of individualized care results suggested that targeting education at responders could be of value. The cost-effectiveness analysis suggested, for all 5 algorithms, that providing structured education to a subgroup of predicted responders would not be cost-effective. LIMITATIONS: . The psychological prediction models tested did not have sufficient predictive power to make targeting treatment cost-effective. The psychological prediction models are simple linear models of psychological behavior. Collection of data on additional covariates could potentially increase statistical power. CONCLUSIONS: . By collecting data on psychological variables before an intervention, we can construct predictive models of treatment response to interventions. These predictive models can be incorporated into health economic models to investigate more complex service delivery and reimbursement strategies. PMID- 26377677 TI - Synthesis and Identification of Pregnenolone Derivatives as Inhibitors of Isozymes of 5alpha-Reductase. AB - Hyperplasia of the prostate gland and prostate cancer have been associated with high levels of serum 5alpha-dihydrotestosterone. This steroid is formed from testosterone by the activity of the enzyme 5alpha-reductase (5alpha-R) present in the prostate. Thus, inhibition of this enzyme could be a goal for therapies to treat these diseases. This study reports the synthesis and effects of five different 21-esters of pregnenolone derivatives as inhibitors of 5alpha-R types 1 and 2. The activity of these steroidal compounds was determined using in vivo and in vitro experiments. The results indicate that of the five steroids studied, the 21(p-fluoro)benzoyloxypregna-4,16-diene-3,6,20-trione derivative, whose structure has not yet been reported, has the best molecular conformation to inhibit the in vitro activity of both types of 5alpha-R. In addition, this steroid also displayed activity in vivo. Apparently, its pharmacological effect was increased by the presence of a keto group at C-6, because this group decreased the possibility that the steroid would be metabolized by hepatic enzymes. In addition, the double bond present at C-4 of this compound also enhanced its inhibitory activity on 5alpha-R, and the C-21 ester moiety increased its liphophilicity. Therefore, its solubility in the cell membrane and its pharmacological activity were both increased. PMID- 26377676 TI - From GTP and G proteins to TRPC channels: a personal account. AB - By serendipity and good fortune, as a postdoctoral fellow in 1967, I landed at the right place at the right time, as I was allowed to investigate the mechanism by which hormones activate the enzyme adenylyl cyclase (then adenyl cyclase) in Martin Rodbell's Laboratory at the NIH in Bethesda, Maryland. The work uncovered first, the existence of receptors separate from the enzyme and then, the existence of transduction mechanisms requiring guanosine-5'-triphosphate (GTP) and Mg(2+). With my laboratory colleagues first and postdoctoral fellows after leaving NIH, I participated in the development of the field "signal transduction by G proteins," uncovered by molecular cloning several G-protein-coupled receptors (GPCRs) and became interested in both the molecular makeup of voltage gated Ca channels and Ca2+ homeostasis downstream of activation of phospholipase C (PLC) by the Gq/11 signaling pathway. We were able to confirm the hypothesis that there would be mammalian homologues of the Drosophila "transient receptor potential" channel and discovered the existence of six of the seven mammalian genes, now called transient receptor potential canonical (TRPC) channels. In the present article, I summarize from a bird's eye view of what I feel were key findings along this path, not only from my laboratory but also from many others, that allowed for the present knowledge of cell signaling involving G proteins to evolve. Towards the end, I summarize roles of TRPC channels in health and disease. PMID- 26377678 TI - Experimental knee pain impairs submaximal force steadiness in isometric, eccentric, and concentric muscle actions. AB - INTRODUCTION: Populations with knee joint damage, including arthritis, have noted impairments in the regulation of submaximal muscle force. It is difficult to determine the exact cause of such impairments given the joint pathology and associated neuromuscular adaptations. Experimental pain models that have been used to isolate the effects of pain on muscle force regulation have shown impaired force steadiness during acute pain. However, few studies have examined force regulation during dynamic contractions, and these findings have been inconsistent. The goal of the current study was to examine the effect of experimental knee joint pain on submaximal quadriceps force regulation during isometric and dynamic contractions. METHODS: The study involved fifteen healthy participants. Participants were seated in an isokinetic dynamometer. Knee extensor force matching tasks were completed in isometric, eccentric, and concentric muscle contraction conditions. The target force was set to 10 % of maximum for each contraction type. Hypertonic saline was then injected into the infrapatella fat pad to generate acute joint pain. The force matching tasks were repeated during pain and once more 5 min after pain had subsided. RESULTS: Hypertonic saline resulted in knee pain with an average peak pain rating of 5.5 +/- 2.1 (0-10 scale) that lasted for 18 +/- 4 mins. Force steadiness significantly reduced during pain across all three muscle contraction conditions. There was a trend to increased force matching error during pain but this was not significant. CONCLUSION: Experimental knee pain leads to impaired quadriceps force steadiness during isometric, eccentric, and concentric contractions, providing further evidence that joint pain directly affects motor performance. Given the established relationship between submaximal muscle force steadiness and function, such an effect may be detrimental to the performance of tasks in daily life. In order to restore motor performance in people with painful arthritic conditions of the knee, it may be important to first manage their pain more effectively. PMID- 26377679 TI - Proteolytic cleavage analysis at the Murray Valley encephalitis virus NS1-2A junction. AB - BACKGROUND: Our understanding of the proteolytic processing events at the NS1-2A junction in the flavivirus polyprotein has not markedly progressed since the early work conducted on dengue virus (DENV). This work identified an octapeptide sequence located immediately upstream of the cleavage site thought to be important in substrate recognition by an as yet unknown, endoplasmic reticulum resident host protease. Of the eight amino acid recognition sequence, the highly conserved residues at positions P1, P3, P5, P7 and P8 (with respect to N-terminus of NS2A) are particularly sensitive to amino acid substitutions in terms of DENV NS1-NS2A cleavage efficiency; however, the role of the octapeptide in efficient NS1 and NS2A production of other flaviviruses has not been experimentally addressed. METHODS AND RESULTS: Using site-directed mutagenesis at the NS1-2A cleavage site of Murray Valley encephalitis virus (MVEV), we confirmed the dominant role of conserved octapeptide residues for efficient NS1-2A cleavage, while changes at variable and the P1' residues were mostly tolerated. However, digressions from the consensus cleavage motif derived from studies on DENV were also found. Thus, comparison of the impact on cleavage of mutations at the NS1-2A junction of MVEV and DENV showed virus-specific differences at both conserved and variable residues. CONCLUSION: We show, with subgenomic expression and infectious clone-derived mutants of MVEV that conserved residues in the flavivirus octapeptide motif can be replaced with a different amino acid without markedly reducing cleavage efficiency of NS1 and NS2A. PMID- 26377680 TI - Down-regulation of microRNA-26a and up-regulation of microRNA-27a contributes to aggressive progression of human osteosarcoma. AB - BACKGROUND: Osteosarcoma is the most common primary bone malignancy with high local aggressiveness and rapid metastasizing potential, resulting in poor survival. Increasing reports suggest that deregulated microRNAs (miRNAs) might provide novel therapeutic targets for cancers. However, the expression of miR-26a and miR-27a in osteosarcoma need further investigation in clinical samples. In our study, we evaluate the expression of these miRNAs in osteosarcoma tissues and compared with paired adjacent non-tumor bone tissues using RT-qPCR. METHODS: Total RNA was purified from patients with osteosarcoma and noncancerous bone tissues. Real-time PCR was applied to quantify the expression level of miR-26a and miR-27a. Moreover, the correlation of these markers with clinicopathological characteristics was also evaluated in osteosarcoma patients. A cox proportional hazards model was performed to assess multivariate analyses of prognostic values. RESULTS: Our result suggested that miR-26aexpression level in osteosarcoma bone tissue was significantly lower than that in the paired noncancerous bone tissues. MiR-27a expression was higher in osteosarcoma bone tissue in comparison with paired noncancerous bone tissues. The results indicated that low expression level of miR-26a and high expression of miR-27a were associated with high TNM stage (P = 0.001; P = 0.012), tumor grade (P = 0.007; P = 0.016), and distant metastasis (P = 0.004; P = 0.001). Kaplan-Meier analysis and log-rank test indicated that patients with low expression of miR-26a and high expression of miR-27a had shorter overall survival (log-rank test: P < 0.001). Multivariate Cox proportional hazards model analysis showed that low expression of miR-26a and high expression of miR-27a (P = 0.021; P = 0.011), high TNM stage (P = 0.001; P = 0.003), tumor grade (P = 0.005; P = 0.01), and distant metastasis.(P = 0.002; P = 0.005) were independent prognostic factors for overall survival patients with osteosarcoma cancer. CONCLUSIONS: In conclusion, our findings suggested that expression level of miR-26a and miR-27a contributes to aggressive progression of this malignancy. Therefore, may have clinical potentials as a non-invasive diagnostic/prognostic biomarker for osteosarcoma patients. PMID- 26377681 TI - Three-pathway combination for glutathione biosynthesis in Saccharomyces cerevisiae. AB - BACKGROUND: Glutathione (GSH), a pivotal non-protein thiol, can be biosynthesized through three pathways in different organisms: (1) two consecutive enzymatic reactions catalyzed by gamma-glutamylcysteine synthetase (Gsh1 or GshA) and glutathione synthetase (Gsh2 or GshB); (2) a bifunctional gamma-glutamylcysteine synthetase/glutathione synthetase (GshF); (3) an alternative condensation of gamma-glutamyl phosphate synthesized by gamma-glutamyl kinase (Pro1 or ProB) with cysteine to form gamma-glutamylcysteine which was further conjugated to glycine by glutathione synthetase. The Gsh1 and Gsh2 of conventional GSH biosynthetic pathway or the bifunctional GshF reported previously have been independently modulated for GSH production. This study developed a novel three-pathway combination method to improve GSH production in Saccharomyces cerevisiae. RESULTS: A bifunctional enzyme GshF of Actinobacillus pleuropneumoniae was functionally expressed in S. cerevisiae and Pro1 in proline biosynthetic pathway was exploited for improving GSH yield. Moreover, two fusion proteins Gsh2-Gsh1 and Pro1-GshB were constructed to increase the two-step coupling efficiency of GSH synthesis by mimicking the native domain fusion of GshF. The engineered strain W303-1b/FGP with three biosynthetic pathways presented the highest GSH concentration (216.50 mg/L) and GSH production of W303-1b/FGP was further improved by 61.37 % when amino acid precursors (5 mM glutamic acid, 5 mM cysteine and 5 mM glycine) were fed in shake flask cultures. In batch culture process, the recombinant strain W303-1b/FGP also kept high efficiency in GSH production and reached an intracellular GSH content of 2.27 % after 24-h fermentation. CONCLUSIONS: The engineered strains harbouring three GSH pathways displayed higher GSH producing capacity than those with individually modulated pathways. Three-pathway combinatorial biosynthesis of GSH promises more effective industrial production of GSH using S. cerevisiae. PMID- 26377682 TI - Occurrence of DNET and other brain tumors in Noonan syndrome warrants caution with growth hormone therapy. AB - Noonan syndrome (NS) is an autosomal dominant developmental disorder caused by mutations in the RAS-MAPK signaling pathway that is well known for its relationship with oncogenesis. An 8.1-fold increased risk of cancer in Noonan syndrome has been reported, including childhood leukemia and solid tumors. The same study found a patient with a dysembryoplastic neuroepithelial tumor (DNET) and suggested that DNET tumors are associated with NS. Herein we report an 8-year old boy with genetically confirmed NS and a DNET. Literature review identified eight other reports, supporting the association between NS and DNETs. The review also ascertained 13 non-DNET brain tumors in individuals with NS, bringing to 22 the total number of NS patients with brain tumors. Tumor growth while receiving growth hormone (GH) occurred in our patient and one other patient. It is unknown whether the development or progression of tumors is augmented by GH therapy, however there is concern based on epidemiological, animal and in vitro studies. This issue was addressed in a 2015 Pediatric Endocrine Society report noting there is not enough data available to assess the safety of GH therapy in children with neoplasia-predisposition syndromes. The authors recommend that GH use in children with such disorders, including NS, be undertaken with appropriate surveillance for malignancies. Our case report and literature review underscore the association of NS with CNS tumors, particularly DNET, and call attention to the recommendation that clinicians treating NS patients with GH do so with awareness of the possibility of increased neoplasia risk. PMID- 26377683 TI - The Double-Reduction Landscape in Tetraploid Potato as Revealed by a High-Density Linkage Map. AB - The creation of genetic linkage maps in polyploid species has been a long standing problem for which various approaches have been proposed. In the case of autopolyploids, a commonly used simplification is that random bivalents form during meiosis. This leads to relatively straightforward estimation of recombination frequencies using maximum likelihood, from which a genetic map can be derived. However, autopolyploids such as tetraploid potato (Solanum tuberosum L.) may exhibit additional features, such as double reduction, not normally encountered in diploid or allopolyploid species. In this study, we produced a high-density linkage map of tetraploid potato and used it to identify regions of double reduction in a biparental mapping population. The frequency of multivalents required to produce this degree of double reduction was determined through simulation. We also determined the effect that multivalents or preferential pairing between homologous chromosomes has on linkage mapping. Low levels of multivalents or preferential pairing do not adversely affect map construction when highly informative marker types and phases are used. We reveal the double-reduction landscape in tetraploid potato, clearly showing that this phenomenon increases with distance from the centromeres. PMID- 26377684 TI - Bacterial social interactions drive the emergence of differential spatial colony structures. AB - BACKGROUND: Social interactions have been increasingly recognized as one of the major factors that contribute to the dynamics and function of bacterial communities. To understand their functional roles and enable the design of robust synthetic consortia, one fundamental step is to determine the relationship between the social interactions of individuals and the spatiotemporal structures of communities. RESULTS: We present a systematic computational survey on this relationship for two-species communities by developing and utilizing a hybrid computational framework that combines discrete element techniques with reaction diffusion equations. We found that deleterious interactions cause an increased variance in relative abundance, a drastic decrease in surviving lineages, and a rough expanding front. In contrast, beneficial interactions contribute to a reduced variance in relative abundance, an enhancement in lineage number, and a smooth expanding front. We also found that mutualism promotes spatial homogeneity and population robustness while competition increases spatial segregation and population fluctuations. To examine the generality of these findings, a large set of initial conditions with varying density and species abundance was tested and analyzed. In addition, a simplified mathematical model was developed to provide an analytical interpretation of the findings. CONCLUSIONS: This work advances our fundamental understanding of bacterial social interactions and population structures and, simultaneously, benefits synthetic biology for facilitated engineering of artificial microbial consortia. PMID- 26377685 TI - Determining appropriate timing of adaptive radiation therapy for nasopharyngeal carcinoma during intensity-modulated radiation therapy. AB - BACKGROUND: To determine appropriate timing of an adaptive radiation therapy (ART) replan by evaluating anatomic and dosimetric changes of target volumes and organs at risk (OARs) during intensity-modulated radiation therapy (IMRT) for nasopharyngeal carcinoma (NPC). METHODS: Nineteen NPC patients were recruited. Each patient had repeat computed tomography (CT) scans after each five fractions and at treatment completion. Automatic re-contouring the targets and OARs by using deformable registration algorithm was conducted through CT-CT fusion. Anatomic changes were assessed by comparing the initial CT and repeated CT. Hybrid plans with re-contouring were generated and the dose-volume histograms (DVH) of the hybrid plan and the original plan were compared. RESULTS: Progressive volume reductions in gross target volume for primary disease (GTVnx), gross target volume for involved lymph nodes (GTVnd), and parotids were observed over time. Comparing with the original plan, each hybrid plan had no significant difference in homogeneity index (HI) for all the targets. Some parameters for planning target volumes for primary disease and high-risk clinical target volume (PTVnx and PTV1, respectively) improved significantly, notably starting from the 10th fraction. These parameters included mean dose (Dmean), dose to 95% of the volume (D95), percentage of the volume receiving 95% of the prescription dose (V95), and conformity index (CI) for PTVnx, and Dmean, D95, and CI for PTV1. The dosimetric parameters for PTVnd remained the same in general except for D95 and V95 which had significant improvement at specific time points; whereas for PTV2, similar trend of dosimetric changes was also observed. Dose to some OARs increased significantly at some time points. CONCLUSIONS: There were significant anatomic and dosimetric changes in the targets and OARs. The target dose coverage in the hybrid plans did not get worse, but overdose occurred in some critical structures. Significant dosimetric changes should be considered as a trigger point at which ART replanning is indicated. D95/V95/CI for PTV2, Dmax for the brain stem, spinal cord, right eyeball and left lens, and Dmean/V30 for the parotids and glottis were taken into account for predicting the need for ART. Two replans at the 5th and 15th fractions were suggested. PMID- 26377687 TI - Scaling-Free Electrochemical Production of Caustic and Oxygen for Sulfide Control in Sewers. AB - Caustic shock-loading and oxygen injection are commonly used by the water industry for biofilm and sulfide control in sewers. Caustic can be produced onsite from wastewater using a two-compartment electrochemical cell. This avoids the need for import and storage of caustic soda, which typically represents a cost and a hazard. An issue limiting the practical implementation of this approach is the occurrence of membrane scaling due to the almost universal presence of Ca(2+) and Mg(2+) in wastewater. It results in a rapid increase in the cell voltage, thereby increasing the energy consumption of the system. Here, we propose and experimentally demonstrate an innovative solution for this problem involving the inclusion of a middle compartment between the anode and cathode compartments. Caustic was efficiently produced from wastewater over a period of 12 weeks and had an average Coulombic efficiency (CE) of 84.1 +/- 1.1% at practically relevant caustic strengths (~3 wt %). Neither membrane scaling nor an increase in the cell voltage was observed throughout the experiments. In addition, dissolved oxygen was produced in the anode, resulting in continuously oxygenated wastewater leaving the three-compartment cell. This membrane-scaling control strategy represents a major step forward toward practical implementation of on-site simultaneous electrochemical caustic and oxygen generation for sulfide control in sewers and also has the potential to be applied to other (bio)electrochemical systems receiving wastewater as source for product recovery. PMID- 26377686 TI - Behavioral, Cognitive, and Motor Preparation Deficits in a Visual Cued Spatial Attention Task in Autism Spectrum Disorder. AB - Abnormalities in motor skills have been regarded as part of the symptomatology characterizing autism spectrum disorder (ASD). It has been estimated that 80 % of subjects with autism display "motor dyspraxia" or clumsiness that are not readily identified in a routine neurological examination. In this study we used behavioral measures, event-related potentials (ERP), and lateralized readiness potential (LRP) to study cognitive and motor preparation deficits contributing to the dyspraxia of autism. A modified Posner cueing task was used to analyze motor preparation abnormalities in children with autism and in typically developing children (N = 30/per group). In this task, subjects engage in preparing motor response based on a visual cue, and then execute a motor movement based on the subsequent imperative stimulus. The experimental conditions, such as the validity of the cue and the spatial location of the target stimuli were manipulated to influence motor response selection, preparation, and execution. Reaction time and accuracy benefited from validly cued targets in both groups, while main effects of target spatial position were more obvious in the autism group. The main ERP findings were prolonged and more negative early frontal potentials in the ASD in incongruent trials in both types of spatial location. The LRP amplitude was larger in incongruent trials and had stronger effect in the children with ASD. These effects were better expressed at the earlier stages of LRP, specifically those related to response selection, and showed difficulties at the cognitive phase of stimulus processing rather that at the motor execution stage. The LRP measures at different stages reflect the chronology of cognitive aspects of movement preparation and are sensitive to manipulations of cue correctness, thus representing very useful biomarker in autism dyspraxia research. Future studies may use more advance and diverse manipulations of movement preparation demands in testing more refined specifics of dyspraxia symptoms to investigate functional connectivity abnormalities underlying motor skills deficits in autism. PMID- 26377688 TI - RNA and protein expression of herpesvirus entry mediator (HVEM) is associated with molecular markers, immunity-related pathways and relapse-free survival of patients with AML. AB - Immune checkpoint molecules are highly relevant as potential prognostic markers and therapeutic targets in malignant diseases. HVEM belongs to the TNF receptor family and provides stimulatory as well as inhibitory signals depending on the ligand. Abnormal HVEM expression has been described in various malignancies, but the role in AML is unknown. Here we report extensive data on HVEM surface protein expression analyzed by flow cytometry on bone marrow leukemic cells of 169 AML patients at diagnosis. An independent cohort of 512 AML patients was analyzed for HVEM mRNA expression in bone marrow samples by Affymetrix microarrays. Consistently for both cohorts and methods, we show that HVEM was differentially expressed and that expression levels were associated with defined genetic markers. HVEM expression was lower in cases with FLT3-ITD (p = 0.001, p < 0.001), with mutations in NPM1 (p = 0.001, p < 0.001) or with the combination of NPM1 mutation and FLT3 wild type (p = 0.049, p = 0.050), while a biallelic mutation in CEBPA correlated positively with higher HVEM expression (p = 0.015, p < 0.001). In a differential gene expression analysis, we found 13 genes including HOXA9, MEIS1 and MN1 that were closely associated with HVEM expression. Besides, four gene sets closely linked to immunity were enriched in HVEM (high) samples. Finally, high expression of HVEM was associated with a trend toward longer relapse-free survival. The results of this study provide new information on the potential significance of HVEM in AML. PMID- 26377689 TI - Immunotherapy with dendritic cells loaded with glioblastoma stem cells: from preclinical to clinical studies. AB - Different approaches have been explored to raise effective antitumor responses against glioblastoma (GBM), the deadliest of primary brain tumors. In many clinical studies, cancer vaccines have been based on dendritic cells (DCs) loaded with peptides, representing one or more specific tumor antigens or whole lysates as a source of multiple antigens. Randomized clinical trials using DCs are ongoing, and results of efficacy are not yet available. Such strategies are feasible and safe; however, immune-suppressive microenvironment, absence of appropriate specific epitopes to target, and cancer immunoediting can limit their efficacy. The aim of this review is to describe how the definition of novel and more specific targets may increase considerably the possibility of successful DC immunotherapy. By proposing to target glioblastoma stem-like cells (GSCs), the immune response will be pointed to eradicating factors and pathways highly relevant to GBM biology. Preclinical observations on efficacy, and preliminary results of immunotherapy trials, encourage exploring the clinical efficacy of DC immunotherapy in GBM patients using high-purity, GSC-loaded DC vaccines. PMID- 26377690 TI - Association of KCNB1 polymorphisms with lipid metabolisms and insulin resistance: a case-control design of population-based cross-sectional study in Chinese Han population. AB - BACKGROUND: In our previous study, we had assessed in the Chinese Han population the association of KCNB1 rs1051295 with metabolic traits indicating metabolic syndrome, and showed that KCNB1 rs1051295 genotype TT was associated with increase of waist to hip ratio (WHR), fasting insulin (FINS), triglycerides (TG) and decreased insulin sensitivity at basal condition. Here, we aimed at detecting whether there were associations between other tag SNPs of KCNB1 and favorable or unfavorable metabolic traits. METHODS: We conducted a case-control design of population-based cross-sectional study to investigate the association between each of the 22 candidates tag SNPs of KCNB1 and metabolic traits in a population of 733 Chinese Han individuals. The association was assessed by multiple linear regression analysis or unconditional logistic regression analysis. RESULTS: We found that among the 22 selected tag SNPs, four were associated with an increase (rs3331, rs16994565) or decrease (rs237460, rs802950) in serum cholesterol levels; two of these (rs237460, rs802590) further associated or were associated with reduced serum LDL-cholesterol. Two novel tag SNPs (rs926672, rs1051295) were associated with increased serum TG levels. We also showed that KCNB1 rs926672 associated with insulin resistance by a case-control study, and two tag SNPs (rs2057077and rs4810952) of KCNB1 were associated with the measure of insulin resistance (HOMA-IR) in a cross-section study. CONCLUSION: These results indicate that KCNB1 is likely associated with metabolic traits that may either predispose or protect from progression to metabolic syndrome. This study provides initial evidence that the gene variants of KCNB1, encoding Kv2.1 channel, is associated with perturbation of lipid metabolism and insulin resistance in Chinese Han population. PMID- 26377691 TI - Treatment of livestock with systemic insecticides for control of Anopheles arabiensis in western Kenya. AB - BACKGROUND: Despite the implementation of vector control strategies, including insecticide-treated bed nets (ITN) and indoor residual spraying (IRS) in western Kenya, this area still experiences high level of malaria transmission. Novel vector control tools are required which target such vector species, such as Anopheles arabiensis, that feed outdoors and have minimal contact with ITNs and IRS. METHODS: To address this need, ivermectin, eprinomectin, and fipronil were evaluated in Zebu cattle under semi-field conditions to evaluate the potential of these compounds to reduce the survival of blood feeding An. arabiensis. Over the course of four experiments, lactating cattle received doses of oral ivermectin at 0.1 or 0.2 mg/kg, oral eprinomectin at 0.2 or 0.5 mg/kg, topical eprinomectin at 0.5, 0.75, or 1.5 mg/kg, or oral fipronil at 0.25, 0.5, 1.0, or 1.5 mg/kg. On days 1, 3, 5, 7, 14, and 21 days post-treatment, cattle were exposed to An. arabiensis, and mosquito mortality post-blood feeding was monitored. For the analysis of survival data, the Kaplan-Meier estimator and Mantel-Haenszel test was used to contrast the treatment and control survival functions. RESULTS: All three compounds significantly reduced the survival time of An. arabiensis. Twenty one days post-treatment, mortality of mosquitoes fed on cattle dosed orally with 0.2 or 0.5 mg/kg eprinomectin, topically with eprinomectin at 0.5 mg/kg, or orally with either 1.0 or 1.5 mg/kg fipronil was still significantly higher than control mortality. CONCLUSIONS: These data demonstrate the effectiveness of three insecticidal compounds administered systemically to cattle for controlling the cattle-feeding mosquito An. arabiensis. Eprinomectin and fipronil provided the longest-lasting control. Such endectocidal treatments in cattle are a promising new strategy for control of residual, outdoor malaria transmission and could effectively augment current interventions which target more endophilic vector species. PMID- 26377692 TI - A case series of acute renal infarction at a single center in Japan. AB - BACKGROUND: The prevalence of acute renal infarction (ARI) in Japan remains unclear. We describe the clinical features and renal prognosis of ARI in Japanese patients. METHODS: This single-center, retrospective, observational study included 33 patients with newly diagnosed ARI (2009-2013). Their clinical features and long-term renal outcomes were evaluated. RESULTS: The prevalence of ARI among emergency room patients was 0.013 %. The incidence of ARI among in patients was 0.003 % (mean age 71.9 +/- 13.4 years; men 63 %). Enhanced computed tomography or renal isotope scans were obtained to diagnose ARI. ARI involved the left kidney in 70 %, right kidney in 18 %, and both kidneys in 12 % of patients. Four cases had splenic infarction, and 70 % of patients had atrial fibrillation. We noted abdominal or flank pain in 66 %, fever (>37.6 degrees C) in 36 %, and nausea/vomiting in 6 % of patients. The white blood cell count, and levels of lactate dehydrogenase and C-reactive protein peaked at 2-4 days after onset. Acute kidney injury due to ARI occurred in 76 % of patients. The estimated glomerular filtration rate decreased to ~70 % and recovered to ~80 % of the original value after 1 year. The mortality rates were 9 and 15 % at 1 month and 1 year, respectively. CONCLUSIONS: We determined the prevalence of ARI among emergency room patients, its incidence among in-patients, and short-term and long term mortality. The majority of ARI cases were of cardiac origin, and the others were due to trauma or systemic thrombotic disease. Clinicians should recognize ARI as a fatal arterial thrombotic disease. PMID- 26377693 TI - Comparative transcriptomic analyses to scrutinize the assumption that genotoxic PAHs exert effects via a common mode of action. AB - In this study, the accuracy of the assumption that genotoxic, carcinogenic polycyclic aromatic hydrocarbons (PAHs) act via similar mechanisms of action as benzo(a)pyrene (BaP), the reference PAH used in the human health risk assessment of PAH-containing complex mixtures, was investigated. Adult male MutaTMMouse were gavaged for 28 days with seven individual, genotoxic PAHs. Global gene expression profiles in forestomach, liver, and lung (target tissues of exposure) were determined at 3 days post-exposure. The results are compared with our previously published results from mice exposed to BaP via the same exposure regimen. Although all PAHs showed enhanced ethoxyresorufin-O-deethylase activity, DNA adduct formation, and lacZ mutant frequency in the lungs, the unsupervised cluster analysis of differentially expressed genes revealed that the transcriptional changes are both PAH- and tissue-specific, with lung showing the most response. Further bioinformatics-/pathway-based analysis revealed that all PAHs induce expression of genes associated with carcinogenic processes, including DNA damage response, immune/inflammatory response, or cell signaling processes; however, the type of pathways and the magnitude of change varied for each PAH and were not the same as those observed for BaP. Benchmark dose modeling showed transcriptomic data closely reflected the known tumor incidence for the individual PAHs in each tissue. Collectively, the results suggest that the underlying mechanisms of PAH-induced toxicity leading to tumorigenesis are tissue specific and not the same for all PAHs; based on the tissue type considered, use of BaP as a reference chemical may overestimate or underestimate the carcinogenic potential of PAHs. PMID- 26377694 TI - A comprehensive overview of hepatoprotective natural compounds: mechanism of action and clinical perspectives. AB - Hepatoprotective effects of natural compounds have been frequently attributed to their antioxidant properties and the ability to mobilize endogenous antioxidant defense system. Because of involvement of oxidative stress in virtually all mechanisms of liver injury, it is a reasonable presumption that antioxidant properties of these compounds may play a key role in the mechanism of their hepatoprotective activity. Nevertheless, growing evidence suggests that other pharmacological activities of natural compounds distinct from antioxidant are responsible for their therapeutic effects. In this review, we discussed currently known molecular mechanisms of the hepatoprotective activity of 27 most intensively studied phytochemicals. These compounds have been shown to possess anti-inflammatory, antisteatotic, antiapoptotic, cell survival and antiviral activity through interference with multiple molecular targets and signaling pathways. Additionally, antifibrotic properties of phytochemicals have been closely associated with apoptosis of hepatic stellate cells and stimulation of extracellular matrix degradation. However, although these compounds exhibit a pronounced hepatoprotective effects in animal and cell culture models, the lack of clinical studies remains a bottleneck for their official acceptance by medical experts and physicians. Therefore, controlled clinical trials have an imperative in confirmation of the therapeutic activity of potentially hepatoprotective compounds. Understanding the principles of the hepatoprotective activity of phytochemicals could guide future drug development and help prevention of clinical trial failure. Also, the use of new delivery systems that enhances bioavailability of poorly water soluble compounds may improve the results already obtained. Most importantly, available data suggest that phytochemicals possess a various degree of modulation of specific signaling pathways, pointing out a need for usage of combinations of several hepatoprotective compounds in both experimental studies and clinical trials. PMID- 26377695 TI - Non-Ataxic Presenting Symptoms of Dominant Ataxias. AB - While the onset of a dominantly inherited ataxia is typically taken to be the onset of gait ataxia, a wide range of other symptoms related to central and/or peripheral nervous system impairment, or even to non-neurological involvement, can be the presenting feature. Knowledge of these is fairly robust for the commonest spinocerebellar ataxias (SCAs 1, 2, 3 and 6) and for those where a striking non-ataxic presentation is the norm (SCAs 7 and 12), but the literature is potentially misleading in the rarer dominant ataxias. This review summarises what is currently known of these non-ataxic presentations and outlines and explains the difficulties associated with determining non-ataxic presentations of dominant ataxias. The relevant literature was surveyed, including systematic reviews (where available) and case reports. Non-ataxic presentations of dominant ataxias are classified by symptom. PMID- 26377696 TI - The carotenoid cleavage dioxygenase CCD2 catalysing the synthesis of crocetin in spring crocuses and saffron is a plastidial enzyme. AB - The apocarotenoid crocetin and its glycosylated derivatives, crocins, confer the red colour to saffron. Crocetin biosynthesis in saffron is catalysed by the carotenoid cleavage dioxygenase CCD2 (AIG94929). No homologues have been identified in other plant species due to the very limited presence of crocetin and its derivatives in the plant kingdom. Spring Crocus species with yellow flowers accumulate crocins in the stigma and tepals. Four carotenoid CCDs, namely CaCCD1, CaCCD2 and CaCCD4a/b and CaCCD4c were first cloned and characterized. CaCCD2 was localized in plastids, and a longer CCD2 version, CsCCD2L, was also localized in this compartment. The activity of CaCCD2 was assessed in Escherichia coli and in a stable rice gene function characterization system, demonstrating the production of crocetin in both systems. The expression of all isolated CCDs was evaluated in stigma and tepals at three key developmental stages in relation with apocarotenoid accumulation. CaCCD2 expression parallels crocin accumulation, but C14 apocarotenoids most likely are associated to the CaCCD1 activity in Crocus ancyrensis flowers. The specific CCD2 localization and its membrane interaction will contribute to the development of a better understanding of the mechanism of crocetin biosynthesis and regulation in the chromoplast. PMID- 26377697 TI - Clinical presentation and memory function in youth with type 1 diabetes. AB - OBJECTIVE: While cerebral edema and diabetic ketoacidosis (DKA) in type 1 diabetes (T1DM) have well-described acute effects on cognition, little is known about the impact of clinical presentation on longer term cognitive outcomes. We hypothesized that clinical factors (degree of hyperglycemia exposure and DKA) at the time of diagnosis would relate to cognition within 3.5 months later in children with T1DM. METHODS: Cognitive testing was performed on children 7-17 years old with T1DM (n = 66) within 3.5 months of diagnosis and siblings without T1DM (n = 33). Overall intelligence, processing speed, and memory (including a sensitive long-delay spatial memory test; spatial delayed response or SDR) were assessed. Medical records were reviewed for hemoglobin A1c (HbA1c), DKA status, and other clinical factors at diagnosis. RESULTS: Within the group with T1DM, 17 children presented in DKA and 49 did not. After adjusting for age, gender, and socioeconomic status, the subgroup with T1DM and DKA at diagnosis performed worse on the long-delay SDR task compared to sibling controls (p = 0.006). In addition, within the group with T1DM, higher HbA1c at diagnosis was associated with worse performance on the long-delay SDR task (p = 0.027). Performance on the other cognitive tasks was not different across groups or subgroups. CONCLUSIONS: DKA and degree of hyperglycemia exposure at diagnosis have implications for long delay spatial memory function within 3.5 months of diagnosis. These findings suggest that early detection of T1DM, which decreases risk for prolonged exposure to hyperglycemia and DKA, may avoid negative effects on memory function. PMID- 26377698 TI - Synkinesis assessment in facial palsy: validation of the Dutch Synkinesis Assessment Questionnaire. AB - The objective of this study is to validate an existing health-related quality of life questionnaire for patients with synkinesis in facial palsy for implementation in the Dutch language and culture. The Synkinesis Assessment Questionnaire was translated into the Dutch language using a forward-backward translation method. A pilot test with the translated questionnaire was performed in 10 patients with facial palsy and 10 normal subjects. Finally, cross-cultural adaption was accomplished at our outpatient clinic for facial palsy. Analyses for internal consistency, test-retest reliability, and construct validity were performed. Sixty-six patients completed the Dutch Synkinesis Assessment Questionnaire and the Dutch Facial Disability Index. Cronbach's alpha, representing internal consistency, was 0.80. Test-retest reliability was 0.53 (Spearman's correlation coefficient, P < 0.01). Correlations with the House Brackmann score, Sunnybrook score, Facial Disability Index physical function, and social/well-being function were -0.29, 0.20, -0.29, and -0.32, respectively. Correlation with the Sunnybrook synkinesis subscore was 0.50 (Spearman's correlation coefficient). The Dutch Synkinesis Assessment Questionnaire shows good psychometric values and can be implemented in the management of Dutch speaking patients with facial palsy and synkinesis in the Netherlands. Translation of the instrument into other languages may lead to widespread use, making evaluation, and comparison possible among different providers. PMID- 26377699 TI - Nervous system Lyme disease, chronic Lyme disease, and none of the above. AB - Lyme borreliosis, infection with the tick-borne spirochete Borrelia burgdorferi sensu lato, causes nervous system involvement in 10-15 % of identified infected individuals. Not unlike the other well-known spirochetosis, syphilis, infection can be protracted, but is microbiologically curable in virtually all patients, regardless of disease duration. Diagnosis relies on 2-tier serologic testing, which after the first 4-6 weeks of infection is both highly sensitive and specific. After this early, acute phase, serologic testing should rely only on IgG reactivity. Nervous system involvement most commonly presents with meningitis, cranial neuritis and radiculoneuritis, but can also present with a broader array of peripheral nervous system manifestations. Central nervous system infection typically elicits a cerebrospinal fluid pleocytosis and, often, intrathecal production of specific antibody, findings that should not be expected in disease not affecting the CNS. Treatment with recommended courses of oral or, when necessary, parenteral antibiotics is highly effective. The attribution of chronic, non-specific symptoms to "chronic Lyme disease", in the absence of specific evidence of ongoing B. burgdorferi infection, is inappropriate and unfortunate, leading not only to unneeded treatment and its associated complications, but also to missed opportunities for more appropriate management of patients' often disabling symptoms. PMID- 26377701 TI - The income inequality hypothesis rejected? PMID- 26377702 TI - Influence of two administration rates of alfaxalone at induction on its relative potency in cats: a pilot study. AB - Objectives The aim of the study was to evaluate, in a controlled, randomised, masked clinical trial, the influence of administration rate of alfaxalone at induction on its relative potency in cats and to report the incidence of cardiorespiratory adverse effects. Methods Twelve healthy female domestic cats admitted for ovariohysterectomy were premedicated with buprenorphine 20 ug/kg intramuscularly and alfaxalone 3.0 mg/kg subcutaneously. Sedation scores were established (using a published scale ranging from 1 [no sedation] to 5 [profound sedation]) prior to anaesthesia induction with alfaxalone intravenously at 2 mg/kg/min (group A2; n = 6) or 0.5 mg/kg/min (group A0.5; n = 6) to effect until orotracheal intubation was achieved. Sedation scores and alfaxalone induction doses were compared between the groups, using a Mann-Whitney exact test. Results are reported as median and range. Presence of apnoea (no breathing for more than 30 s) or hypotension (mean arterial blood pressure <60 mmHg) within 5 mins postintubation was also reported. Results Although sedation scores (1.5 [range 1.0-3.0] and 2.5 [range 1.0-3.0] for A2 and A0.5, respectively) were not significantly different ( P = 0.32), cats in group A2 required significantly more alfaxalone (4.3 mg/kg [range 3.4-7.0 mg/kg]) than group A0.5 (2.1 mg/kg [range 1.5-2.5 mg/kg]) ( P = 0.002). Two cats in each group presented postinduction apnoea, and two cats in group A2 and three cats in group A0.5 presented postinduction hypotension. Conclusions and relevance The use of a slower induction infusion rate resulted in an increase in the alfaxalone relative potency without obvious cardiorespiratory benefit. PMID- 26377703 TI - Presumptive acute non-compressive nucleus pulposus extrusion in 11 cats: clinical features, diagnostic imaging findings, treatment and outcome. AB - Objectives The aim of the study was to describe the clinical features, diagnostic imaging findings, treatment and outcome in cats diagnosed with presumptive acute non-compressive nucleus pulposus extrusion. Methods Medical records and imaging studies of cats diagnosed with presumptive acute non-compressive nucleus pulposus extrusion were retrospectively reviewed. Information on long-term outcome was acquired from patient records and from either owners or referring veterinary surgeons via a telephone questionnaire. Results Eleven cats met the inclusion criteria. All cats had a peracute onset of clinical signs, with eight cats experiencing witnessed (n = 6) or suspected (n = 2) external trauma based on imaging findings. Neuroanatomical localisation included C1-C5 (n = 1), T3-L3 (n = 7) and L4-S3 (n = 3) spinal cord segments. MRI revealed acute non-compressive nucleus pulposus extrusions located at C3-C4 (n = 1), T12-T13 (n = 1), T13-L1 (n = 1), L1-L2 (n = 1), L3-L4 (n = 3), L4-L5 (n = 1) and L5-L6 intervertebral disc spaces (n = 3). Treatment included supportive care and 10 cats were discharged with a median hospitalisation time of 10 days (range 3-26 days). One cat was euthanased during hospitalisation owing to complications unrelated to neurological disease. All cats that presented as non-ambulatory regained an ambulatory status with the median time to ambulation of 17 days (range 6-21 days). Overall, the outcome for cats diagnosed with acute non-compressive nucleus pulposus extrusion was successful, with almost 90% returning to ambulation with urinary and faecal continence. Conclusions and relevance The majority of cats diagnosed with acute non-compressive nucleus pulposus extrusion had good outcomes. Acute non-compressive nucleus pulposus extrusion should be considered as a differential diagnosis for cats presenting with peracute onset of spinal cord dysfunction, particularly if there is a clinical history or evidence of trauma. PMID- 26377700 TI - Maternal obesity during pregnancy and cardiovascular development and disease in the offspring. AB - Maternal obesity during pregnancy is an important public health problem in Western countries. Currently, obesity prevalence rates in pregnant women are estimated to be as high as 30%. In addition, approximately 40% of women gain an excessive amount of weight during pregnancy in Western countries. An accumulating body of evidence suggests a long-term impact of maternal obesity and excessive weight gain during pregnancy on adiposity, cardiovascular and metabolic related health outcomes in the offspring in fetal life, childhood and adulthood. In this review, we discuss results from recent studies, potential underlying mechanisms and challenges for future epidemiological studies. PMID- 26377704 TI - Efficient Pd-catalyzed domino synthesis of 1-phenyl-1H-indol-2-amine and 5-amino indolo[1,2-a]quinazoline derivatives. AB - An efficient and practical one-pot domino synthesis of 1-phenyl-1H-indol-2-amine and 5-amino-indolo[1,2-a]quinazoline derivatives from readily available 2-(2 bromophenyl)acetonitriles was developed. The overall protocol involves a Buchwald Hartwig type coupling and a base-promoted intramolecular nucleophilic reaction. The reaction scope, advantages and limitations are discussed. PMID- 26377706 TI - Introduction to the 2015 Supplement to Cardiology in the Young: Proceedings of the 2015 International Pediatric Heart Failure Summit of Johns Hopkins All Children's Heart Institute. AB - In the United States of America alone, ~14,000 children are hospitalised annually with acute heart failure. The science and art of caring for these patients continues to evolve. The International Pediatric Heart Failure Summit of Johns Hopkins All Children's Heart Institute was held on 4 and 5 February, 2015. The 2015 International Pediatric Heart Failure Summit of Johns Hopkins All Children's Heart Institute was funded through the Andrews/Daicoff Cardiovascular Program Endowment, a philanthropic collaboration between All Children's Hospital and the Morsani College of Medicine at the University of South Florida (USF). Sponsored by All Children's Hospital Andrews/Daicoff Cardiovascular Program, the Johns Hopkins All Children's Heart Institute International Pediatric Heart Failure Summit assembled leaders in clinical and scientific disciplines related to paediatric heart failure and created a multi-disciplinary "think-tank". Information about George R. Daicoff, MD, and Ed and Sarainne Andrews is provided in this introductory manuscript to the 2015 Supplement to Cardiology in the Young entitled: "Proceedings of the 2015 International Pediatric Heart Failure Summit of Johns Hopkins All Children's Heart Institute". Dr Daicoff founded the All Children's Hospital Pediatric Heart Surgery programme and directed this programme for over two decades. Sarainne Andrews made her generous bequest to All Children's Hospital in honour of her husband Ed and his friendship with Dr Daicoff in order to support cardiovascular surgery research efforts. PMID- 26377705 TI - Suicidal Ideation and Behaviours Among Adolescents Receiving Bariatric Surgery: A Case-Control Study. AB - OBJECTIVE: This study examined the prevalence and correlates of suicidal ideation and behaviour (SI/B) among adolescents receiving bariatric surgery. METHOD: Charts of 206 adolescents receiving bariatric surgery were reviewed. Cases with SI/B (current/lifetime reported at baseline or event occurring in the programme n = 31, 15%) were case matched on gender, age and surgery type to 31 adolescents reporting current or past psychiatric treatment and 31 adolescents denying lifetime SI/B or psychiatric treatment. RESULTS: Before surgery, adolescents with SI/B reported significantly lower total levels of health-related quality of life (p = 0.01) and greater depressive symptoms (p = 0.004) in comparison with candidates who never received psychiatric treatment. No significant differences were found between groups for the change in depressive symptoms or body mass index following surgery. CONCLUSIONS: As in studies of adults, a notable subset of adolescents receiving bariatric surgery indicated pre-operative or post operative SI/B. It is critical that clinicians evaluate and monitor adolescent patients undergoing bariatric surgery for risk of SI/B. PMID- 26377707 TI - Summary of the 2015 International Paediatric Heart Failure Summit of Johns Hopkins All Children's Heart Institute. AB - In the United States alone, ~14,000 children are hospitalised annually with acute heart failure. The science and art of caring for these patients continues to evolve. The International Pediatric Heart Failure Summit of Johns Hopkins All Children's Heart Institute was held on February 4 and 5, 2015. The 2015 International Pediatric Heart Failure Summit of Johns Hopkins All Children's Heart Institute was funded through the Andrews/Daicoff Cardiovascular Program Endowment, a philanthropic collaboration between All Children's Hospital and the Morsani College of Medicine at the University of South Florida (USF). Sponsored by All Children's Hospital Andrews/Daicoff Cardiovascular Program, the International Pediatric Heart Failure Summit assembled leaders in clinical and scientific disciplines related to paediatric heart failure and created a multi disciplinary "think-tank". The purpose of this manuscript is to summarise the lessons from the 2015 International Pediatric Heart Failure Summit of Johns Hopkins All Children's Heart Institute, to describe the "state of the art" of the treatment of paediatric cardiac failure, and to discuss future directions for research in the domain of paediatric cardiac failure. PMID- 26377708 TI - Nomenclature and systems of classification for cardiomyopathy in children. AB - There has been a progressive evolution in systems of classification for cardiomyopathy, driven by advances in imaging modalities, disease recognition, and genetics, following initial clinical descriptions in the 1960s. A pathophysiological classification emerged and was endorsed by World Health Organisation Task Forces in 1980 and 1995: dilated, hypertrophic, restrictive, and arrhythmogenic right ventricular cardiomyopathies; subdivided into idiopathic and disease-specific cardiomyopathies. Genetic advances have increasingly linked "idiopathic" phenotypes to specific mutations, although most linkages exhibit highly variable or little genotype-phenotype correlation, confounded by age dependent changes and varying penetrance. The following two dominant classification systems are currently in use, with advocates in both continents. First, American Heart Association (2006): "A heterogeneous group of diseases of the myocardium associated with mechanical and/or electrical dysfunction that usually exhibit inappropriate ventricular hypertrophy or dilatation due to a variety of causes that frequently are genetic". These are subdivided to those predominantly involving the heart - primary - due to genetic mutation, including ion channelopathies, acquired disease, or mixed; and those with systemic involvement in other organ systems - secondary. Second, European Society of Cardiology (2008): "A myocardial disorder in which heart muscle is structurally and functionally abnormal... sufficient to cause the observed myocardial abnormality", with subdivision to familial and non-familial, excluding ion channelopathies, and split to specific disease subtypes and idiopathic. Further differences exist in the definitions for hypertrophic cardiomyopathy; however, whichever high-level classification is used, the clinical reality remains phenotype driven. Clinical evaluation and diagnostic imaging dominate initial patient contact, revealing diagnostic red flags that determine further specific tests. Genetic testing is undertaken early. A recent attempt to harmonise these competing systems named the MOGE(S) system, based on descriptive logical nosology, currently remains unproven as a fully practical solution. PMID- 26377709 TI - Evaluation of genetic causes of cardiomyopathy in childhood. AB - Cardiomyopathy frequently has a genetic basis. In adults, mutations in genes encoding components of the sarcomere, cytoskeleton, or desmosome are frequent genetic causes of cardiomyopathy. Although children share these causes, ~30% of children have an underlying metabolic, syndromic, or neuromuscular condition causing their cardiomyopathy, making the aetiologies more diverse in children as compared with adults. Although some children present with obvious signs or symptoms of metabolic, syndromic, or neuromuscular disease, other cases may be quite subtle, requiring a high level of suspicion in order to diagnose them. In general, the younger the child, the more extensive the differential. Advantages of identifying the underlying genetic cause of cardiomyopathy in the paediatric population include confirming the diagnosis in ambiguous cases, facilitating appropriate surveillance and management of cardiac and extra-cardiac diseases, providing prognostic information, and establishing the genetic basis in the family, thereby allowing the identification of at-risk relatives and institution of appropriate family screening as indicated. For these reasons, genetic testing is increasingly recognised as standard of care, and guidelines for genetic counselling, testing, and incorporation of family-based risk assessment have been established. Therapies aimed at treating specific genetic aetiologies of cardiomyopathy are emerging and are exciting new developments that require increasingly sophisticated approaches to diagnosis. As genetic testing capabilities continue to expand technically, careful interpretation, knowledgeable clinical utilisation, and appropriate dissemination of genetic information are important and challenging components of clinical care. PMID- 26377710 TI - Proteomics of pediatric heart failure: from traditional biomarkers to new discovery strategies. AB - Heart failure in children is a complex clinical syndrome with multiple aetiologies. The underlying disorders that lead to heart failure in children differ significantly from those in adults. Some clinical biomarkers for heart failure status and prognosis appear to be useful in both age groups. This review outlines the use and the present status of biomarkers for heart failure in paediatric cardiology. Furthermore, clinical scenarios in which development of new biomarkers might address management or prognosis are discussed. Finally, strategies for proteomic discovery of novel biomarkers and application to practice are described. PMID- 26377712 TI - Clinical management of patients with acute heart failure. AB - Acute heart failure is a common and serious complication of congenital and acquired heart disease, and it is associated with significant morbidity, mortality, and costs. When a patient is admitted to the hospital with acute heart failure, there are several important goals for the hospital admission, including maintaining adequate perfusion, establishing the underlying aetiology for the heart failure, patient and family education, and discharge from the hospital in a stable condition. The pathway to home discharge is variable and may include inotropic therapy, mechanical circulatory support, and/or heart transplantation. This review will cover the epidemiology, presentation, and management of acute heart failure in children. PMID- 26377711 TI - Stem cell therapy for CHD: towards translation. AB - Stem cell therapy has the optimistic goal of regenerating the myocardium as defined by re-growth of lost or destroyed myocardium. As applied to patients with heart failure, many confuse or limit the regenerative definition to just improving myocardial function and/or decreasing myocardial scar formation, which may not be the most important clinical outcome to achieve in this promising field of molecular medicine. Many different stem cell-based therapies have been tested and have demonstrated a safe and feasible profile in adult patients with heart failure, but with varied efficacious end points reported. Although not achieved as of yet, the encompassing goal to regenerate the heart is still believed to be within reach using these cell-based therapies in adult patients with heart failure, as the first-generation therapies are now being tested in different phases of clinical trials. Similar efforts to foster the translation of stem cell therapy to children with heart failure have, however, been limited. In this review, we aim to summarise the findings from pre-clinical models and clinical experiences to date that have focussed on the evaluation of stem cell therapy in children with heart failure. Finally, we present methodological considerations pertinent to the design of a stem cell-based trial for children with heart failure, as they represent a population of patients with very different sets of issues when compared with adult patients. As has been taught by many learned clinicians, children are not small adults! PMID- 26377713 TI - Critical care for paediatric patients with heart failure. AB - This review offers a critical-care perspective on the pathophysiology, monitoring, and management of acute heart failure syndromes in children. An in depth understanding of the cardiovascular physiological disturbances in this population of patients is essential to correctly interpret clinical signs, symptoms and monitoring data, and to implement appropriate therapies. In this regard, the myocardial force-velocity relationship, the Frank-Starling mechanism, and pressure-volume loops are discussed. A variety of monitoring modalities are used to provide insight into the haemodynamic state, clinical trajectory, and response to treatment. Critical-care treatment of acute heart failure is based on the fundamental principles of optimising the delivery of oxygen and minimising metabolic demands. The former may be achieved by optimising systemic arterial oxygen content and the variables that determine cardiac output: heart rate and rhythm, preload, afterload, and contractility. Metabolic demands may be decreased by a number of ways including positive pressure ventilation, temperature control, and sedation. Mechanical circulatory support should be considered for refractory cases. In the near future, monitoring modalities may be improved by the capture and analysis of complex clinical data such as pressure waveforms and heart rate variability. Using predictive modelling and streaming analytics, these data may then be used to develop automated, real-time clinical decision support tools. Given the barriers to conducting multi-centre trials in this population of patients, the thoughtful analysis of data from multi-centre clinical registries and administrative databases will also likely have an impact on clinical practice. PMID- 26377714 TI - Echocardiographic evaluation of the failing heart. AB - Heart failure in children can result from a wide range of aetiologies and can manifest in systolic and/or diastolic dysfunction. Echocardiography is the primary test for the diagnosis and follow-up of children with heart failure. In this article, we critically review standard echocardiographic measurements that have been shown to have prognostic importance in children with various types of heart failure. Each of the common forms of cardiomyopathy that is encountered in childhood--dilated, hypertrophic, restrictive, left ventricular non-compaction, and arrhythmogenic right ventricular cardiomyopathy--is discussed separately. Special attention is paid to the failing right ventricle, both in the systemic and in the sub-pulmonary position, to the failing univentricular heart, and to the assessment of diastolic function in children. PMID- 26377715 TI - Advanced functional echocardiographic imaging of the failing heart in children. AB - Over the past decade, new echocardiographic techniques such as three-dimensional echocardiography and the imaging of myocardial deformation (strain) have been developed, and are increasingly used in clinical practice. In this article, we describe the rationale and methodology, review available guidelines for practice, and discuss the advantages and limitations of each of these modalities. When available, we have also summarised the scientific evidence for the clinical application of these techniques to detect heart failure in children. PMID- 26377716 TI - Diagnosis and treatment of foetal heart failure: foetal echocardiography and foetal hydrops. AB - Foetal echocardiography has progressed to be able to diagnose many forms of CHD and to assess the prognosis of cardiac lesions based on their anatomy and presentation in utero. This article outlines a straightforward method for the rapid evaluation of foetus that may have congestive heart failure with or without hydrops and for the differentiation of the pre-hydropic state from normal. The presence of signs of foetal heart failure, such as cardiomegaly or valvular regurgitation, gives clues to the aetiology of hydrops. The assessment of the prognosis of hydrops foetalis can be difficult but can be aided by the use of the cardiovascular profile score. Once identified, the neurohumoral effects of foetal heart failure can be ameliorated using transplacental digoxin if the hydrops has not progressed. PMID- 26377718 TI - Emerging science in paediatric heart transplantation: donor allocation, biomarkers, and the quest for evidence-based medicine. AB - Heart transplantation offers excellent survival benefit to children with end stage heart failure. With its success, the number of potential recipients continues to exceed the number of available donors. Developing strategies to safely increase donor utilisation is crucial to decreasing wait-list mortality. A new paediatric heart allocation policy is set to be implemented with the goal of prioritising the most urgent listed candidates. Owing to excellent outcomes of ABO-incompatible heart transplantation, the sickest infants will soon receive priority for heart offers irrespective of blood group. Allosensitisation poses unique challenges within the paediatric population; ongoing multi-centre studies are poised to refine our understanding of key risk factors and optimal treatment strategies. Biomarkers for acute cellular rejection, such as donor-specific cell free DNA, and cardiac allograft vasculopathy, such as VEGF-A, may lead to a decreased need for invasive screening. Ultimately, well-designed and executed randomised control trials of post-transplant immunosuppression are required to improve long-term outcomes after paediatric heart transplantation. PMID- 26377717 TI - Cardiac complications in childhood cancer survivors treated with anthracyclines. AB - Cardiovascular complications are among the leading causes of morbidity and mortality among survivors of childhood cancer, after cancer relapse and secondary malignancies. Although advances in cancer treatment have improved the 5-year survival rates, the same treatments, such as anthracyclines, that cure cancer also increase the risk for adverse cardiovascular effects. Anthracycline-related cardiotoxicity in survivors of childhood cancer is progressive and can take years to develop, initially presenting as sub-clinical cardiac abnormalities that, if left undetected or untreated, can lead to heart failure, myocardial infarction, or other clinical cardiac dysfunction. A higher cumulative dose of anthracycline is associated with cardiotoxicity in children; however, sub-clinical cardiac abnormalities are evident at lower doses with longer follow-up, suggesting that there is no "safe" dose of anthracycline. Other risk factors include female sex, younger age at diagnosis, black race, trisomy 21, longer time since treatment, and the presence of pre-existing cardiovascular disease and co-morbidities. Cardioprotective strategies during treatment are limited in children. Enalapril provides only temporary cardioprotection, whereas continuous anthracycline infusion extends none. On the other hand, dexrazoxane successfully prevents or reduces anthracycline-related cardiotoxicity in children with cancer, without increased risks for recurrence of primary or second malignancies or reductions in anti-tumour efficacy. With more childhood cancer survivors now reaching adulthood, it is vital to understand the adverse effects of cancer treatment on the cardiovascular system and their long-term consequences to identify and establish optimal prevention and management strategies that balance oncologic efficacy with long-term safety. PMID- 26377719 TI - Heart Failure Summit Review: cardiac re-synchronisation therapy in the failing heart. AB - Extrapolating cardiac resynchronization therapy (CRT) to pediatric patients with heart failure has at times been difficult given the heterogeneity of pediatric cardiomyopathies, varying congenital heart disease (CHD) substrates, and the fact that most pediatric heart failure patients have right bundle branch block (RBBB) as opposed to LBBB. Yet, despite these limitations a number of multi-center retrospective studies in North America and Europe have identified some data to suggest that certain sub-populations tend to respond positively to CRT. In order to address some of the heterogeneity it is helpful to subdivide pediatric and young adult patients with CHD into four potential groups: (1) CRT for chronic RV pacing, (2) dilated cardiomyopathies, (3) pulmonary right ventricles, and (4) systemic right ventricles. The chronic RV paced group, especially long-standing RV apical pacing, with ventricular dyssynchrony has consistently shown to be the group that best responds to a proactive resynchronization course. CRT therapy in pulmonary right ventricles such as post-op tetralogy of Fallot have shown some promise and may be considered especially if there is evidence of concomitant left ventricular dysfunction with an electrical dyssynchrony. Patients with systemic right ventricles such as post-atrial baffle surgery or congenitally corrected transposition reportedly do well with CRT in the presence of both inter ventricular and intra-ventricular dyssynchrony. There is little doubt that moving forward to best way to identify which pediatric patients with heart failure will respond to CRT, will require a collaborative effort between the electrophysiologist and the echocardiographer to identify appropriate candidates with electrical and mechanical dyssynchrony. PMID- 26377720 TI - More lessons learned from the Pediatric Heart Transplant Study. AB - Paediatric heart transplantation has evolved over the last 3 decades. The research group, Pediatric Heart Transplant Study, has been in step with that evolution over the nearly 20 years of its existence by utilising its registry to contribute a wealth of clinical research to the field. The highlights of its studies will be presented in this review. PMID- 26377721 TI - Lessons learned from the Pediatric Cardiomyopathy Registry (PCMR) Study Group. AB - Cardiomyopathy is a rare disorder of the heart muscle, affecting 1.13 cases per 100,000 children, from birth to 18 years of age. Cardiomyopathy is the leading cause of heart transplantation in children over the age of 1. The Pediatric Cardiomyopathy Registry funded in 1994 by the National Heart, Lung, and Blood Institute was established to examine the epidemiology of the disease in children below 18 years of age. More than 3500 children across the United States and Canada have been enrolled in the Pediatric Cardiomyopathy Registry, which has followed-up these patients until death, heart transplantation, or loss to follow up. The Pediatric Cardiomyopathy Registry has provided the most in-depth illustration of this disease regarding its aetiology, clinical course, associated risk factors, and patient outcomes. Data from the registry have helped in guiding the clinical management of cardiomyopathy in children under 18 years of age; however, questions still remain regarding the most clinically effective diagnostic and treatment approaches for these patients. Future directions of the registry include the use of next-generation whole-exome sequencing and cardiac biomarkers to identify aetiology-specific treatments and improve diagnostic strategies. This article provides a brief synopsis of the work carried out by the Pediatric Cardiomyopathy Registry since its inception, including the current knowledge on the aetiologies, outcomes, and treatments of cardiomyopathy in children. PMID- 26377722 TI - Review of the International Society for Heart and Lung Transplantation Practice guidelines for management of heart failure in children. AB - In 2004, practice guidelines for the management of heart failure in children by Rosenthal and colleagues were published in conjunction with the International Society for Heart and Lung Transplantation. These guidelines have not been updated or reviewed since that time. In general, there has been considerable controversy as to the utility and purpose of clinical practice guidelines, but there is general recognition that the relentless progress of medicine leads to the progressive irrelevance of clinical practice guidelines that do not undergo periodic review and updating. Paediatrics and paediatric cardiology, in particular, have had comparatively minimal participation in the clinical practice guidelines realm. As a result, most clinical practice guidelines either specifically exclude paediatrics from consideration, as has been the case for the guidelines related to cardiac failure in adults, or else involve clinical practice guidelines committees that include one or two paediatric cardiologists and produce guidelines that cannot reasonably be considered a consensus paediatric opinion. These circumstances raise a legitimate question as to whether the International Society for Heart and Lung Transplantation paediatric heart failure guidelines should be re-reviewed. The time, effort, and expense involved in producing clinical practice guidelines should be considered before recommending an update to the International Society for Heart and Lung Transplantation Paediatric Heart Failure guidelines. There are specific areas of rapid change in the evaluation and management of heart failure in children that are undoubtedly worthy of updating. These domains include areas such as use of serum and imaging biomarkers, wearable and implantable monitoring devices, and acute heart failure management and mechanical circulatory support. At the time the International Society for Heart and Lung Transplantation guidelines were published, echocardiographic tissue Doppler, 3 dimensional imaging, and strain and strain rate were either novel or non-existent and have now moved into the main stream. Cardiac magnetic resonance imaging (MRI) had very limited availability, and since that time imaging and assessment of myocardial iron content, delayed gadolinium enhancement, and extracellular volume have moved into the mainstream. The only devices discussed in the International Society for Heart and Lung Transplantation guidelines were extracorporeal membrane oxygenators, pacemakers, and defibrillators. Since that time, ventricular assist devices have become mainstream. Despite the relative lack of randomised controlled trials in paediatric heart failure, advances continue to occur. These advances warrant implementation of an update and review process, something that is best done under the auspices of the national and international cardiology societies. A joint activity that includes the International Society for Heart and Lung Transplantation, American College of Cardiology/American Heart Association, the Association for European Paediatric and Congenital Cardiology (AEPC), European Society of Cardiology, Canadian Cardiovascular Society, and others will have more credibility than independent efforts by any of these organisations. PMID- 26377723 TI - Can linking databases answer questions about paediatric heart failure? AB - Numerous data sets collect information on patients with paediatric cardiovascular disease, including paediatric heart failure and transplant patients. This review discusses methodologies available for linking and integrating information across data sets, which may help facilitate answering important questions in the field of paediatric heart failure and transplant that cannot be answered with individual data sets or single-centre data alone. PMID- 26377724 TI - Paediatric heart failure research: role of the National Heart, Lung, and Blood Institute. AB - The National Heart, Lung, and Blood Institute, of the National Institutes of Health, is committed to supporting research in paediatric heart failure. The Institute's support of paediatric heart failure research includes both investigator-initiated grants and Institute initiatives. There were 107 funded grants in paediatric heart failure over the past 20 years in basic, translational and clinical research, technology development, and support of registries. Such research includes a broad diversity of scientific topics and approaches. The Institute also supports several initiatives for paediatric heart failure, including the Pediatric Circulatory Support Program, the Pumps for Kids, Infants, and Neonates (PumpKIN) Program, PediMACS, and the Pediatric Heart Network. This review article describes the National Heart, Lung, and Blood Institute's past, present, and future efforts to promote a better understanding of paediatric heart failure, with the ultimate goal of improving outcomes. PMID- 26377726 TI - General practitioners' anticipated risk of cancer at referral and their attitude to risk taking and to their role as gatekeeper. AB - OBJECTIVES: General practitioners have to deal with situations characterized by real but low likelihoods of serious illness. We aimed to investigate variations in general practitioners' anticipated risk of cancer when referring a patient and associations both with general practitioners' attitudes to risk taking and with their gatekeeper role. METHODS: In January 2012, all 835 active general practitioners in the county of Aarhus, Denmark, received a questionnaire including the Physician Reaction to Uncertainty scale, The Tolerance for Ambiguity scale, the Physician Risk Attitude scale and a number of single items assessing anticipated risk of cancer when referring a hypothetical 50-year-old patient, use of intuition and perception of their role as a gatekeeper. RESULTS: A total of 568 (68.0%) practitioners completed and returned the questionnaire. The median anticipated risk of cancer was 30% (inter-quartile range: 15%-50%) and the 5%-95% centiles were 5% and 80%. Increasing tolerance for ambiguity was strongly related to a declining anticipated risk of cancer. None of the other risk attitudes were associated with the anticipated risk of cancer at referral. Increased general practitioners' age was related to increased anticipated risk of cancer when referring (25% for general practitioners under 45 years to 43% for those 60 years or over) but not statistically important. CONCLUSIONS: General practitioners either overestimate the risk of cancer when referring for suspected cancer or they appear to need to be very sure of the cancer diagnosis before referral. Further, focus on tolerance for ambiguity should be included in the education of general practitioners. PMID- 26377725 TI - Paediatric cardiovascular clinical trials: an analysis of ClinicalTrials.gov and the Food and Drug Administration Pediatric Drug Labeling Database. AB - Recent regulatory initiatives in the United States of America and Europe have transformed the paediatric clinical trials landscape by significantly increasing capital investment and paediatric trial volume. The purpose of this manuscript was to review the impact of these initiatives on the paediatric cardiovascular trials landscape when compared with other paediatric sub-specialties. We also evaluate factors that may have contributed to the success or failure of recent major paediatric cardiovascular trials so as to inform the optimal design and conduct of future trials in the field. PMID- 26377728 TI - Improving access: modifying Penchansky and Thomas's Theory of Access. AB - Access is defined as the degree of fit between the user and the service; the better the fit, the better the access. Using the theory developed by Penchansky and Thomas, access is optimized by accounting for the different dimensions of access: accessibility; availability; acceptability; affordability; and adequacy in service design, implementation and evaluation. These dimensions are independent yet interconnected and each is important to assess the achievement of access. However, I argue that one dimension is missing - awareness. I propose that awareness is integral to access, that it should become a permanent part of the theory, and be applied whenever using the theory to develop, implement, or evaluate health care services and access more generally. PMID- 26377727 TI - The PRISMS taxonomy of self-management support: derivation of a novel taxonomy and initial testing of its utility. AB - BACKGROUND: Supporting self-management is a core response of health care systems globally to the increasing prevalence of long-term conditions. Lack of a comprehensive taxonomy (or classification) of self-management support components hinders characterization and, ultimately, understanding of these frequently complex, multi-component interventions. OBJECTIVE: To develop a comprehensive, descriptive taxonomy of self-management support components. METHODS: Components were derived from the 969 unique randomized controlled trials described in the 102 systematic reviews and 61 implementation trials, examining 14 diverse long term conditions included in the Practical Reviews in Self-Management Support (PRISMS) project followed by discussion at an expert stakeholder workshop. The utility of the taxonomy was then tested using a self-management support intervention for cancer survivors. RESULTS: The PRISMS taxonomy comprises 14 components that might be used to support self-management (e.g. information about condition/management, provision of equipment, social support), when delivered to someone with a long-term condition or their carer. Overarching dimensions are delivery mode; personnel delivering the support; intervention targeting; and intensity, frequency and duration of the intervention. The taxonomy does not consider the effectiveness or otherwise of the different components or the overarching dimensions. CONCLUSIONS: The PRISMS taxonomy offers a framework to researchers describing self-management support interventions, to reviewers synthesizing evidence and to developers of health services for people with long term conditions. PMID- 26377729 TI - Reflecting on the impact of health services research on society. PMID- 26377730 TI - Evolution of the premaxillary fraenum and substratum in snubnose darters and allies (Percidae: Etheostoma). AB - Darters (Percidae: Etheostomatinae), a species-rich group of North American freshwater fishes, vary in the presence of a premaxillary fraenum, a strip of skin that connects the premaxillary bones to the snout, and it is hypothesized that this trait is a trophic adaptation to particular substrata. Ancestral state reconstructions and analyses of phylogenetic associations between presence of the premaxillary fraenum and preferred stream substratum were conducted in a clade of closely related darters (snubnose darters and allies) that vary in morphology and habitat preferences. The most recent common ancestor of this clade was inferred to possess a fraenum and to inhabit rocky substrata, consistent with previous hypotheses, but a significant correlation between fraenum presence and substratum type across the phylogeny was not found. PMID- 26377731 TI - Thinned chimeric radial collateral artery perforator flap in complex distal thumb reconstruction. AB - INTRODUCTION: Tissue loss accompanied by bone defects in the thumb is a challenging reconstruction problem. Traditional repair methods are unsatisfactory. METHODS: Microsurgical thumb reconstruction was performed using 13 thinned chimeric radial collateral artery (RCA) perforator flaps. The flap was created with a thinned skin paddle and humeral bone segments using independent perforators. Primary defatting was completed when the thickness of the perforator entry was approximately similar to that in the periphery. The posterior cutaneous nerve of the arm was carried to make a sensory flap. Defects were 8.5 * 4.5 cm(2) on average (ranging in size from 4.5 * 1.5 to 15.0 * 6.0 cm(2)), and flap size was 9.0 * 5.5 cm(2) on average (ranging in size from 5.0 * 2.0 to 16.0 * 7.0 cm(2)), whereas the humeral fragments were 2.0 * 1.0 cm(2) on average (ranging in size from 1.5 * 0.5 to 4.0 * 1.5 cm(2)). All data were expressed as mean +/- SD. The cosmetic appearance of the donor and recipient sites, Kapandji opposition score and static two-point discrimination of the operated thumb were evaluated during a follow-up visit. RESULTS: Follow-up time was 16.6 months (ranging from 14 to 28 months). Flap thickness before defatting, measured immediately after flap elevation was 14.5 mm (ranging from 10.0 to 25.0 mm). Average flap thickness after defatting was 3.5 mm (ranging from 3.0 to 6.0 mm). Venous congestion occurred in two cases. Successful microsurgical revision was achieved in both cases. All flaps survived. Bone components achieved union in all cases at an average period of 4.8 months (ranging from 3 to 6 months). Based on Kapandji opposition score, the mean thumb opposition score was 6. The mean sensation of flap was 7.5 mm (ranging from 6 to 11 mm). No further flap revision or defatting procedures were required in all cases. Cosmetically acceptable results were achieved for all patients. CONCLUSIONS: Findings proved that thinned chimeric RCA perforator flap is a beneficial microsurgical alternative for reconstructing complex bone and soft tissue defects in thumb. PMID- 26377732 TI - Early rehospitalization after hip fracture in elderly patients: risk factors and prognosis. AB - INTRODUCTION: Hip fracture usually occurs in older patients. These patients remain at risk for developing new medical complications even after discharge from the hospital. The objective of this study was to identify risk factors for hospital readmission 30 days after hip fracture and the prognosis of the readmitted patients. MATERIALS METHODS: A prospective, observational cohort study of 732 consecutive patients over 65 years surgically treated for hip fracture and discharged alive in 2010-2014 was conducted. The measurements were patient demographic characteristics, residential and discharge status, Katz Index, Merle D'aubigne Hip Score, Mini-Mental Test, comorbid conditions, Charlson Index, ASA group, type of fracture and repair, and postoperative complications. Patient characteristics were tested by bivariate and multivariate analyses. RESULTS: 8.3 % of patients were readmitted within 30 days (56.0 % of these within 2 weeks). Medical reasons were 13 times more frequent than surgical reasons. Diagnoses more prevalent for readmission were pulmonary disease, deep vein thrombosis, heart failure, and renal failure. Predictors of readmission were female gender (HR 1.9, 95 % CI 1.1-3.4), grade III-IV ASA (HR 2.1, 95 % CI 1.1-4.2), and pre-existing pulmonary disease (HR 5.3, 95 % CI 3.4-9.6). In-hospital mortality among readmitted patients was 22.9 %. In bivariate analyses, male gender, ASA III-IV, cognitive impairment, and more than two comorbidities were potential predictive factors for readmission, and in multivariate analysis only male gender and ASA III-IV. Mortality risk among readmitted patients was significantly higher compared to the in-hospital mortality in the overall cohort (OR 1.8, 95 % CI 1.5 2.3). CONCLUSIONS: Hospital readmissions after hip fracture were mainly due to medical complications and a fraction of these may be preventable. Readmission was associated with increased morbidity and mortality. PMID- 26377733 TI - Dual mini-fragment plating for midshaft clavicle fractures: a clinical and biomechanical investigation. AB - BACKGROUND: We sought to evaluate clinical and biomechanical outcomes of dual mini-fragment plate fixation for clavicle fractures. We hypothesized that this technique would produce an anatomical reduction with good clinical outcomes, be well tolerated by patients, and demonstrate equivalent biomechanics to single plating. METHODS: Dual mini-fragment plating was performed for 17 isolated, displaced midshaft clavicle fractures. Functional outcomes and complications were retrospectively reviewed. A sawbones model compared dual plating biomechanics to a (1) superior 3.5-mm locking reconstruction plate, or (2) antero-inferior 3.5-mm locking reconstruction plate. RESULTS: On biomechanical testing, with anterior loading, dual plating was significantly more rigid than single locked anterior plating (p = 0.02) but less rigid than single locked superior-plating (p = 0.001). With superior loading, dual plating trended toward higher rigidity versus single locked superior-plating (p = 0.07) but was less rigid than single locked anterior-plating (p = 0.03). No statistically significant differences in axial loading (p = 0.27) or torsion (p = 0.23) were detected. Average patient follow-up was 16.1 months (12-38). Anatomic reduction was achieved and maintained through final healing (average 14.7 weeks). No patient underwent hardware removal. Average 1-year DASH score was 4.0 (completed in 88 %). CONCLUSIONS: Displaced midshaft clavicle fractures can be effectively managed with dual mini-fragment plating. This technique results in high union rates and excellent clinical outcomes. Compared to single plating, dual plating is biomechanically equivalent in axial loading and torsion, yet offers better multi-planar bending stiffness despite the use of smaller plates. This technique may decrease the need for secondary surgery due to implant prominence and may aid in fracture reduction by buttressing butterfly fragments in two planes. PMID- 26377734 TI - Reduction of Dimethylnitrosamine-Induced Liver Fibrosis by the Novel Gene Regulator PI Polyamide Targeting Transforming Growth Factor beta1 Gene. AB - Pyrrole-imidazole (PI) polyamide is a novel gene regulating agent that competitively inhibits transcription factor binding to the promoter of the specific target gene. Liver fibrosis is an integral stage in the development of chronic liver disease, and transforming growth factor beta (TGFbeta) is known to play a central role in the progression of this entity. The aim of this study was to evaluate the effect of PI polyamide targeting TGFbeta1 on rat liver fibrosis. PI polyamide was designed to inhibit activator protein 1 (AP-1) transcription factor binding to the TGFbeta1 gene promoter. The effect of PI polyamide on hepatic stellate cells was evaluated by real time polymerase chain reaction (PCR) in RI-T cells. To determine the effect of PI polyamide in vivo, PI polyamide was intravenously administered at a dose of 3 mg/kg/week in dimethylnitrosamine (DMN) induced rat model of liver fibrosis. Treatment of RI-T cells with 1.0 uM PI polyamide targeting TGFbeta1 significantly inhibited TGFbeta1 mRNA expression. Azan staining showed that DMN treatment significantly increased areas of fibrous materials compared with controls. PI polyamide targeting TGFbeta1 significantly decreased the fibrous area compared with DMN group. mRNA expression levels of alpha-smooth muscle actin and matrix metalloproteinase-2 were significantly increased in DMN-treated group compared with control. Treatment with TGFbeta1 PI polyamide significantly decreased mRNA expression of these genes compared with DMN group. The novel gene regulator PI polyamide targeting TGFbeta1 may be a feasible therapeutic agent for the treatment of chronic liver disease. PMID- 26377735 TI - Factors Affecting Ethanol-Induced Conditioned Place Preference and Locomotor Sensitization in Mice. AB - The rewarding effects of alcohol can lead to progressively heavier and more frequent drinking. Since studies of reward have mainly focused on responses to higher alcohol doses, the relations between reward and moderate/sustained alcohol exposure remain unknown. Our objective was to evaluate factors affecting the reward value of low alcohol doses and risk factors for increasing alcohol doses due to reward progression caused by alcohol exposure patterns. We thus performed conditioned place preference (CPP) and ethanol (EtOH)-induced locomotor sensitization tests in mice. Low-dose EtOH (0.5 or 1 g/kg twice/week)-induced CPP was stronger than that produced by saline control treatment, but the effect decreased with increasing numbers of conditioning trials. Moderate-dose/long-term EtOH exposure induced a weaker CPP than high-dose/short-term EtOH (2 g/kg twice/week) exposure with the same total EtOH dose (8 g/kg/experiment). Acamprosate calcium, an anti-relapse drug, preclusively reduced EtOH-induced CPP. EtOH induced CPP and locomotor sensitization in black but not white chamber, although the initial preference and the basal locomotion in each chamber were equal. Therefore the brightness of the chamber had an effect on EtOH-induced sensitization. Moreover, additional studies indicated that EtOH-induced locomotor sensitization also depends on the dose but not the administration interval. Paired associative learning with EtOH exposure is a potent factor influencing the level of reward produced by EtOH. Moreover, exposure to high doses of alcohol, even on an intermittent schedule, carries a higher risk of addiction than exposure to moderate doses over longer periods. PMID- 26377736 TI - Mapping the plasmonic response of gold nanoparticles embedded in TiO2 thin films. AB - We present the mapping of the plasmonic properties of gold nanoparticles that are embedded in a TiO2 thin film deposited over two different substrates, glass and silicon. An improved electron energy-loss spectroscopy (EELS) imaging technique was used to extract plasmon maps with nanometre resolution. Several representative cases of randomly dispersed NPs have been examined to carefully evaluate surrounding effects on the optical response of such nanostructured material. Data were compared to analytical calculations and showed good agreement. These results validate previous structural and far-field optical results and provide a clear description of the optical phenomena that take place at a nanometre scale in these materials. They are of primary importance for enlightening the way to the fabrication of thin film materials including metallic nanostructures for photovoltaic applications. PMID- 26377737 TI - Prevalence of depression, anxiety and their risk factors in German women with breast cancer in general and gynecological practices. AB - AIMS: To analyze the prevalence of depression, anxiety and their risk factors in German women with breast cancer (BC) in general and gynecological practices (GP, GYP). METHODS: Women initially diagnosed with BC between 2009 and 2013 were identified by 1202 general practitioners and 244 gynecologists in the IMS Disease Analyzer database. They were included only if they had not suffered from depression or an anxiety disorder within the 12 months prior to the index date. The main outcome was the first diagnosis of depression or an anxiety disorder within 5 years after index date. A multivariate Cox regression model was used to predict these diagnoses on the basis of patient characteristics. RESULTS: A total of 24,537 patients in GP were available for the study, as well as 20,018 patients in GYP. The mean age was 65.8 and 62.5 years in GP and GYP, respectively (p value <0.0001). The proportions of depressive or anxiety episodes in the past and the proportion of metastases were higher in GP than in GYP (7.9 vs. 3.6%, and 10.1 vs. 8.6%, p values <0.0001). Within 5 years of follow-up, 36.9% of GP patients and 35.1% of GYP patients had been diagnosed with depression or anxiety. There was a significantly higher risk of depression and/or anxiety in women in the age groups 51-60, 61-70 and >70 years than in women = <50 years (OR between 1.05 and 1.27, all p values lower than 0.0359). Patients with metastases or with previous episodes of depression/anxiety had a higher risk of depression/anxiety (OR = 1.21 and 1.97, p values <0.0001). Finally, women with private health insurance had a lower risk of depression and anxiety (OR = 0.45, p value <0.0001). CONCLUSION: The present study indicates that levels of depression and anxiety increase in German women after diagnosis of BC and may be predicted on the basis of several demographic and clinical characteristics. PMID- 26377739 TI - Immature Reticulocyte Fraction and Absolute Neutrophil Count as Predictor of Hemopoietic Recovery in Patients with Acute Lymphoblastic Leukemia on Remission Induction Chemotherapy. AB - OBJECTIVE: Acute lymphoblastic leukemia (ALL) encompasses a group of lymphoid neoplasms that are more common in children and arise from B-and T-lineage lymphoid precursor cells. The immature reticulocyte fraction (IRF), a new routine parameter in hematology analyzers, can give an indication of hemopoietic recovery like absolute neutrophil count (ANC). The purpose of this study was to evaluate IRF in excess of 5% was considered as IRF recovery. MATERIALS AND METHODS: In this descriptive study, 2.5 to 3 mL of EDTA blood of 45 ALL patients undergoing the remission induction phase of their treatment was sampled and analyzed with a Sysmex XE-5000 on day 1 and every second day thereafter until the day of recovery. ANC of >0.5x109/L on the day corresponding to the first of the three consecutive counts was considered as the day of ANC recovery. IRF recovery was an IRF in excess of 5%. RESULTS: The mean age of the patients was 12.04+/-5.30 years; 25 patients (55.6%) were male and 20 patients (44.4%) were female. On day 1 of induction remission, the mean IRF value was 9.68+/-1.41, while the mean ANC value was 0.077+/-0.061. Mean recovery day for IRF was 11.84+/-7.44 and mean recovery day for ANC was 17.67+/-8.77 (two- tailed p-value <0.0001 with 95% confidence interval). By day 28, out of 45 patients 36 (80%) showed ANC recovery, while 41 (91%) showed IRF recovery. The remaining patients who had not shown recovery by day 28 were further followed up and all of them showed recovery of both parameters by day 39. CONCLUSION: This study concluded that postinduction bone marrow hemopoietic recovery was earlier by IRF than ANC in children with ALL on chemotherapy. PMID- 26377740 TI - Improving outcomes of subthalamic nucleus deep brain stimulation in Parkinson's disease. AB - The subthalamic nucleus (STN) has been a major target of deep brain stimulation (DBS) for Parkinson's disease (PD) over the past 20 years. The benefits of DBS of the STN include: decreased motor fluctuations and bradykinesia, tremor reduction and a reduction in dopaminergic drug requirements and dyskinesias. Despite these overall positive effects, the outcomes of STN DBS can be variable, contributing to the debate over the best DBS target for PD. Here, the authors review the current practice of STN DBS and also review both the existing and emerging technologies that are likely to improve the accuracy and effectiveness of STN DBS for PD. The authors emphasize patient selection, accuracy of electrode placement within the brain and the selection of appropriate stimulation parameters to optimize clinical benefits. PMID- 26377738 TI - Identification of candidate gonadal sex differentiation genes in the chicken embryo using RNA-seq. AB - BACKGROUND: Despite some advances in recent years, the genetic control of gonadal sex differentiation during embryogenesis is still not completely understood. To identify new candidate genes involved in ovary and testis development, RNA-seq was used to define the transcriptome of embryonic chicken gonads at the onset of sexual differentiation (day 6.0/stage 29). RESULTS: RNA-seq revealed more than 1000 genes that were transcribed in a sex-biased manner at this early stage of gonadal differentiation. Comparison with undifferentiated gonads revealed that sex biased expression was derived primarily from autosomal rather than sex-linked genes. Gene ontology and pathway analysis indicated that many of these genes encoded proteins involved in extracellular matrix function and cytoskeletal remodelling, as well as tubulogenesis. Several of these genes are novel candidate regulators of gonadal sex differentiation, based on sex-biased expression profiles that are altered following experimental sex reversal. We further characterised three female-biased (ovarian) genes; calpain-5 (CAPN5), G-protein coupled receptor 56 (GPR56), and FGFR3 (fibroblast growth factor receptor 3). Protein expression of these candidates in the developing ovaries suggests that they play an important role in this tissue. CONCLUSIONS: This study provides insight into the earliest steps of vertebrate gonad sex differentiation, and identifies novel candidate genes for ovarian and testicular development. PMID- 26377741 TI - New paradigms in hepatitis B management: only diamonds are forever. AB - INTRODUCTION: The hepatitis B virus (HBV) causes chronic hepatitis B (CHB) in ~350 million people worldwide who have an increased risk of end-stage liver disease and/or hepatocellular carcinoma. SOURCES OF DATA: Several peer-reviewed papers featuring new approaches to anti-HBV management. Additionally, we also reviewed recent abstract presentations at international congresses. AREAS OF AGREEMENT: There has been great progress in CHB therapy with the development of standard and pegylated interferon (i.e. PEG-IFN) as well as nucleos/tide analogs (NAs). IFN has both antiviral and immunomodulatory effects and through immune mediated destruction of infected hepatocytes offers the possibility of finite therapy. However, this 'killing for a cure' antiviral strategy may not be tolerated in many, especially in cirrhotic patients. NAs inhibit viral reverse transcriptase, have few side effects and prevent liver disease progression, but cannot offer a cure as they have little effect on the resilient HBV covalently closed circular DNA (cccDNA) intermediate. Moreover, NAs such as tenofovir and entecavir offer a high genetic barrier to resistance, but are expensive and not readily available in many global regions. GROWING POINTS: Despite significant treatment advances, there is increased recognition of the need for improved anti HBV treatments, and new virologic tests for monitoring treatment response. AREAS OF CONTROVERSY: The role of quantitative hepatitis B surface antigen, intrahepatic cccDNA levels and viral genotype in selecting treatment candidates and refining NA stopping rules. AREAS TIMELY FOR DEVELOPING NEW RESEARCH: Potential new therapies include viral entry inhibitors, RNA interference technologies (i.e. RNAi) and small molecules that modulate cccDNA transcription, as well as novel immunomodulatory therapies to boost HBV-specific T cell responses. The ultimate goal of new tests and anti-HBV therapies is to reduce the burden and expense of life-long CHB treatment, as 'only diamonds are forever'. PMID- 26377744 TI - The growth of filaments under macromolecular confinement using scaling theory. AB - Quantitatively describing macromolecular confinement is still a challenge. Using the assembly of DNA tiles in a polyacrylamide network as a model, we studied the effect of macromolecular confinement on the growth of the filament by scaling theory. The results show that the confinement regulates the morphology, the initial growth rate v, and the eventual length of the filament Nm. The initial growth rate is dependent on the medium viscosity eta as nu?eta(-0.94), and the filament adjusts its length in the given confined space as Nm? (xi/Rg)(1.8), with xi being the mesh size of the polyacrylamide solution and Rg being the radius of gyration of polyacrylamide. PMID- 26377745 TI - Mechanistic Understanding of the Divergent Cyclizations of o-Alkynylbenzaldehyde Acetals and Thioacetals Catalyzed by Metal Halides. AB - The mechanisms of regiodivergent cyclizations of o-alkynylbenzaldehyde acetals and thioacetals catalyzed by Pd and Pt halides are studied. DFT calculations found that both reactions are initiated by electrophilic activation of the acetylenic moiety instead of the previously proposed metal-triggered C?X (X=O, S) cleavage. Both the regioselective cyclization of the pi-alkyne complex and the chemoselective [1,2]-migration in the carbenoid intermediate were determined as key steps to achieving the observed divergence. For acetal derivatives containing an internal alkyne, the 6-endo-dig cyclization is more favorable and leads to the carbenoid intermediate easily through further steps of C?X fragmentation and carbocation cyclization. Then, from the carbenoid intermediate, the [1,2] migration of sulfur is easier than that of H, Me, and Ph; whereas, a reversed aptitude was predicted for the oxygen analogue, which is consistent with the greater ability of sulfur atoms to stabilize beta-carbocations. However, for precursors containing a terminal alkyne, the 5-exo-dig pathway is preferred and only the 1,2-disubstituted indene product is seen, irrespective of the nature of the acetal; thus, a different product from that reported in the literature is predicted for benzaldehyde acetal with a terminal alkyne at the ortho position. This prediction led us to reconsider some of the reported results and hidden realities were uncovered with solid new experimental evidence. PMID- 26377742 TI - Mind the gap: race/ethnic and socioeconomic disparities in obesity. AB - Race/ethnic and socioeconomic status (SES) disparities in obesity are substantial and may widen in the future. We review nine potential mechanisms that recent research has used to explain obesity disparities. Those nine mechanisms fall into three broad groups-health behaviors, biological factors, and the social environment-which incorporate both proximate and upstream determinants of obesity disparities. Efforts to reduce the prevalence of obesity in the US population and to close race/ethnic and SES disparities in obesity will likely require the use of multifaceted interventions that target multiple mechanisms simultaneously. Unfortunately, relatively few of the mechanisms reviewed herein have been tested in an intervention framework. PMID- 26377746 TI - Outcomes of Australian rural clinical schools: a decade of success building the rural medical workforce through the education and training continuum. AB - INTRODUCTION: The establishment of the rural clinical schools funded through the Commonwealth Department of Health and Ageing (now Department of Health) Rural Clinical Training and Support program over a decade ago has been a significant policy initiative in Australian rural health. This article explores the impacts of this policy initiative and presents the wide range of educational innovations contextualised to each rural community they serve. METHODS: This article reviews the achievements of the Australian rural clinical and regional medical schools (RCS/RMS) through semi-structured interviews with the program directors or other key informants. The questions and responses were analysed according to the funding parameters to ascertain the numbers of students, types of student placements and range of activities undertaken by each university program. RESULTS: Sixteen university medical schools have established 18 rural programs, creating an extensive national network of RCS and RMS in every state and territory. The findings reveal extensive positive impacts on rural and regional communities, curriculum innovation in medical education programs and community engagement activities. Teaching facilities, information technology, video conferencing and student accommodation have brought new infrastructure to small rural towns. Rural clinicians are thriving on new opportunities for education and research. Clinicians continue to deliver clinical services and some have taken on formal academic positions, reducing professional isolation, improving the quality of care and their job satisfaction. This strategy has created many new clinical academics in rural areas, which has retained and expanded the clinical workforce. A total of 1224 students are provided with high-quality learning experiences for long-term clinical placements. These placements consist of a year or more in primary care, community and hospital settings across hundreds of rural and remote areas. Many programs offer longitudinal integrated clerkships; others offer block rotations in general practice and specialist clinics. Nine universities established programs prior to 2004, and these well-established programs are finding graduates who are returning to rural practice. Universities are required to have 25% of the students from a rural background. University admission policies have changed to encourage more applications from rural students. This aspect of the policy implements the extensive research evidence that rural-origin students are more likely to become rural practitioners. Additional capacity for research in RCS has influenced the rural health agenda in fields including epidemiology, population health, Aboriginal health, aged care, mental health and suicide prevention, farming families and climate change. There are strong research partnerships with rural workforce agencies, research centres for early career researchers and PhD students. CONCLUSIONS: The RCS policy initiative has vastly increased opportunities for medical students to have long-term clinical placements in rural health services. Over a decade since the policy has been implemented, graduates are being attracted to rural practice because they have positive learning experiences, good infrastructure and support within rural areas. The study shows the RCS initiative sets the stage for a sustainable future Australian rural medical workforce now requiring the development of a seamless rural clinical training pipeline linking undergraduate and postgraduate medical education. PMID- 26377747 TI - Predictors of psychiatric readmission among patients with bipolar disorder at an academic safety-net hospital. AB - OBJECTIVE: Even with treatment, approximately one-third of patients with bipolar disorder relapse into depression or mania within 1 year. Unfavorable clinical outcomes for patients with bipolar disorder include increased rates of psychiatric hospitalization and functional impairment. However, only a few studies have examined predictors of psychiatric hospital readmission in a sample of patients with bipolar disorder. The purpose of this study was to examine predictors of psychiatric readmission within 30 days, 90 days and 1 year of discharge among patients with bipolar disorder using a conceptual model adapted from Andersen's Behavioral Model of Health Service Use. METHODS: In this retrospective study, univariate and multivariate logistic regression analyses were conducted in a sample of 2443 adult patients with bipolar disorder who were consecutively admitted to a public psychiatric hospital in the United States from 1 January to 31 December 2013. RESULTS: In the multivariate models, several enabling and need factors were significantly associated with an increased risk of readmission across all time periods examined, including being uninsured, having ?3 psychiatric hospitalizations and having a lower Global Assessment of Functioning score. Additional factors associated with psychiatric readmission within 30 and 90 days of discharge included patient homelessness. Patient race/ethnicity, bipolar disorder type or a current manic episode did not significantly predict readmission across all time periods examined; however, patients who were male were more likely to readmit within 1 year. The 30-day and 1-year multivariate models showed the best model fit. CONCLUSION: Our study found enabling and need factors to be the strongest predictors of psychiatric readmission, suggesting that the prevention of psychiatric readmission for patients with bipolar disorder at safety-net hospitals may be best achieved by developing and implementing innovative transitional care initiatives that address the issues of multiple psychiatric hospitalizations, housing instability, insurance coverage and functional impairment. PMID- 26377748 TI - Preventing suicide requires more attention on technology-based crisis support services. PMID- 26377749 TI - N-Acetylcysteine for Huntington's? PMID- 26377750 TI - Have you heard of the 'party drug' GBL (gamma butyrolactone)? A survey of health workers' knowledge of this potentially fatal drug. PMID- 26377752 TI - Architecturally designed Pt-MoS2 and Pt-graphene composites for electrocatalytic methanol oxidation. AB - Thin films consisting of platinum nanoparticles (Pt NPs) with uniform size and distribution have been successfully prepared at a liquid-liquid interface. Apart from the usual substrates like glass, Si etc. the films were also deposited on the surfaces of MoS2 thin films and graphene nanosheets (GNS) respectively, by using a layer-by-layer (LbL) deposition technique to form Pt-MoS2 and Pt-GNS composites. The loading concentration of Pt NPs on MoS2 and GNS can be adjusted by selecting the number and sequence of the component layers during LbL deposition. The Pt thin films, Pt-MoS2 and Pt-GNS nanocomposite thin films are characterized using transmission electron microscopy (TEM), high resolution transmission electron microscopy (HRTEM), energy dispersive X-ray spectrometry (EDS), X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS). TEM results of the composites show that Pt NPs with sizes in the range of 1 to 3 nm are uniformly dispersed on the MoS2/GNS surface. The catalytic activities of Pt and Pt-composites for the reaction of methanol oxidation are studied using cyclic voltammetry and chronoamperometry. Electrochemical studies reveal that both the Pt-MoS2 and Pt-GNS nanocomposites show excellent electrocatalytic activity towards methanol oxidation. Pt-MoS2 and Pt-GNS nanocomposite electrodes show excellent stability for reuse of the catalyst. A probable mechanism of catalysis has been discussed. We propose that the similar architecture reported here would be promising for the synthesis of high performance catalysts for fuel cells, gas phase reactions, and other applications such as sensors. PMID- 26377753 TI - Superficially Porous Particle Based Hydroxypropyl-beta-cyclodextrin Stationary Phase for High-Efficiency Enantiomeric Separations. AB - A superficially porous particle (SPP)-based hydroxypropyl-beta-cyclodextrin (HPBCD) chiral stationary phase (CSP) was produced and its chromatographic performance was compared to both 5 um and 3 um fully porous particle (FPP)-based CSPs. The relative surface coverage of the HPBCD chiral selector on each particle was approximately equal, which resulted in equivalent enantiomeric selectivity (alpha) values on each phase when constant mobile phase conditions were used. Under such conditions, the SPP column resulted in greatly reduced analysis times and three times greater efficiencies compared to the FPP columns. When higher flow rates were used, efficiency gains per analysis times were five times greater for the SPP column compared to the FPP-based columns. When the mobile phases were altered to give similar analysis times on each column, resolution values were doubled for the SPP column. Finally, the novel SPP based HPBCD column proved to be stable for 500 injections under high flow rate (4.5 mL/min) and high pressure (400 bar) conditions used for an ultrafast (~45 sec) enantiomeric separation. PMID- 26377754 TI - Tai Chi Chuan modulates heart rate variability during abdominal breathing in elderly adults. AB - Tai Chi Chuan (TCC) practice is currently intentionally applied in clinical populations, especially those with cardiovascular diseases because of its potential benefits on the autonomic nervous system. The long-term effect of TCC practice on heart rate variability (HRV) remains largely unknown. In this study, we recruited 23 TCC practitioners whose experience averaged approximately 21 years and 19 controls matched by age, sex and education to examine the effect of TCC practice on the autonomic nervous system during a resting state and during an abdominal breathing state. HRV was measured by traditional electrocardiogram (ECG) recording. The results showed that the low frequency, total power frequency, and normalized low frequency components and the low-frequency/high frequency ratio were significantly higher, whereas the normalized high frequency was significantly lower in the TCC practitioners relative to controls during the abdominal breathing state. However, we did not detect any significant difference in the HRV measures during the resting state between the two groups. Additionally, TCC experience did not correlate with HRV components either in the abdominal state or the resting state in the TCC group. Considering all of these findings, we suggest that TCC improves vagal activity and the balance between sympathetic and parasympathetic activity during the relaxation state. This study also provides direct physiological evidence for the role of TCC practice in relaxation. PMID- 26377755 TI - Extracellular stimulation with human "noisy" electromyographic patterns facilitates myotube activity. AB - Electrical stimulation (ES) of skeletal muscle partially mimics the benefits of physical activity. However, the stimulation protocols applied clinically to date, often cause unpleasant symptoms and muscle fatigue. Here, we compared the efficiency of a "noisy" stimulus waveform derived from human electromyographic (EMG) muscle patterns, with stereotyped 45 and 1 Hz electrical stimulations applied to mouse myotubes in vitro. Human gastrocnemius medialis electromyograms recorded from volunteers during real locomotor activity were used as a template for a noisy stimulation, called EMGstim. The stimulus-induced electrical activity, intracellular Ca(2+) dynamics and mechanical twitches in the myotubes were assessed using whole-cell perforated patch-clamp, Ca(2+) imaging and optical visualization techniques. EMGstim was more efficient in inducing myotube cell firing, [Ca(2+)]i changes and contractions compared with more conventional electrical stimulation. Its stimulation strength was also much lower than the minimum required to induce contractions via stereotyped stimulation protocols. We conclude that muscle cells in vitro can be more efficiently depolarized using the "noisy" stochastic stimulation pattern, EMGstim, a finding that suggests a way to favor a higher level of electrical activity in a larger number of cells. PMID- 26377757 TI - Mott Cells in the Peripheral Blood of a Patient with Dengue Fever. PMID- 26377758 TI - WHO Child Growth Standards Are Often Incorrectly Applied to Children Born Preterm in Epidemiologic Research. AB - In epidemiologic research, there is no standard approach for accounting for gestational age (GA) at birth when interpreting postnatal anthropometric data in analyses of cohorts that include children born preterm (CBP). A scoping review was conducted to describe analytical approaches to account for GA at birth when applying the WHO Growth Standards (WHO-GS) to anthropometric data in epidemiologic studies. We searched PubMed, Scopus, MEDLINE, Embase, and Web of Science for studies that applied WHO-GS, included CBP in the study population, had access to data within 1 mo of age, and were published between 2006 and 2015 in English. Of the 80 included studies that used the WHO-GS, 80% (64 of 80) included all children regardless of GA, whereas 20% (16 of 80) restricted analyses that used WHO-GS to term-born children. Among the 64 studies that included all children, 53 (83%) used chronological age and 11 (17%) used corrected age for CBP. Of the 53 studies that used chronological age, 12 (23%) excluded data that were likely contributed by CBP (e.g., very low birth weight or extremely low outlying z scores) and 19 (36%) adjusted for or stratified by GA at birth in regression analyses. In summary, researchers commonly apply WHO-GS to CBP, usually based on chronological age. Methodologic challenges of analyzing data from CBP in the application of WHO-GS were rarely explicitly addressed. Further efforts are required to establish acceptable approaches to account for heterogeneity in GA at birth in the analysis of post-term anthropometric data in epidemiologic research. PMID- 26377759 TI - Increased Snacking and Eating Occasions Are Associated with Higher Energy Intake among Mexican Children Aged 2-13 Years. AB - BACKGROUND: Little is known about the dietary behaviors of Mexican children with regard to frequency, amount, and quality of foods consumed at eating occasions and their impact on total daily energy intake. OBJECTIVES: The objectives were to 1) describe foods consumed across eating occasions and 2) examine whether the number or type of total eating occasions was associated with increased total daily energy intake and differed between 2- to 5-y-old and 6- to 13-y-old Mexican children. METHODS: A nationally representative sample of 5031 children from the 2012 ENSANUT (Encuesta Nacional de Salud y Nutricion) was used to examine the percentage of meals and snacks consumed, mean energy intake from meals and snacks, and the top food groups contributing to meals and snacks. Multivariate linear regression was used to examine the association between meals, snacks, and total eating occasions with daily energy intake for 2- to 5-y-old and 6- to 13-y old children. RESULTS: Eating patterns were similar across age groups (per capita mean intake of 3 meals and 1.4-1.6 snacks/d). Each additional snack was associated with greater increases in mean daily energy for older children (+191 289 kcal/d; P < 0.01) relative to younger children (+102-130 kcal/d; P < 0.01). Likewise, each additional eating occasion was associated with greater increases in mean daily energy for older children (+323 kcal/d; P < 0.01) relative to younger children (+166-261 kcal/d; P < 0.01). In both younger and older children, snacking was prevalent (75% and 68%, respectively). Top food contributors to snacks included fruit, salty snacks, candy, sweetened breads, and cookies. Among older children, whole milk as a snack was partially replaced with soda and sweetened fruit drinks. CONCLUSION: Snacks represent an area for potential improvement in the diets of Mexican children, especially among those aged 6 to 13 y, for whom each additional snack or eating occasion was linked to even greater increases in total daily energy intake. PMID- 26377756 TI - Phosphoinositides in Ca(2+) signaling and excitation-contraction coupling in skeletal muscle: an old player and newcomers. AB - Since the postulate, 30 years ago, that phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P 2) as the precursor of inositol 1,4,5-trisphosphate (Ins(1,4,5)P 3) would be critical for skeletal muscle excitation-contraction (EC) coupling, the issue of whether phosphoinositides (PtdInsPs) may have something to do with Ca(2+) signaling in muscle raised limited interest, if any. In recent years however, the PtdInsP world has expanded considerably with new functions for PtdIns(4,5)P 2 but also with functions for the other members of the PtdInsP family. In this context, the discovery that genetic deficiency in a PtdInsP phosphatase has dramatic consequences on Ca(2+) homeostasis in skeletal muscle came unanticipated and opened up new perspectives in regards to how PtdInsPs modulate muscle Ca(2+) signaling under normal and disease conditions. This review intends to make an update of the established, the questioned, and the unknown regarding the role of PtdInsPs in skeletal muscle Ca(2+) homeostasis and EC coupling, with very specific emphasis given to Ca(2+) signals in differentiated skeletal muscle fibers. PMID- 26377760 TI - Total Iron Bioavailability from the US Diet Is Lower Than the Current Estimate. AB - BACKGROUND: Total (heme and nonheme) iron bioavailability from the US diet has been estimated to be 18% based on a single human absorption study. New data, however, suggest that it may be time to revisit this estimate. OBJECTIVE: We estimated total iron bioavailability from the US diet with the use of our recently reported algorithm that estimates nonheme iron absorption and a conservative value for heme iron absorption. METHODS: We used dietary intake and biomarker information from the NHANES 2001-2002, MyPyramid Equivalents Database, and Food and Nutrient Database for Dietary Studies. The survey package in R software was used to estimate means and CIs, taking into account the strata, primary sampling units, and appropriate survey weight. We implemented 2 different approaches to estimate total iron absorption. In the first approach, we included all survey participants but adjusted the geometric mean of nonheme iron absorption to 15 MUg ferritin/L serum to mimic values of individuals with no iron stores; in the second approach, absorption was estimated for only nonanemic subjects with no iron stores. A total sample size of 6631 was used based on availability of dietary and iron status biomarker data and C-reactive protein concentration <= 6 mg/L. RESULTS: The geometric mean (95% CI) of unadjusted nonheme iron absorption for all subjects was 3.7% (3.6%, 3.8%), higher in female subjects [5.6% (5.4%, 5.7%)] than male subjects [2.6% (2.5%, 2.7%)] (P < 0.0001). Nonheme iron absorption was lower in non-Hispanic whites [3.5% (3.4%, 3.6%)] than Mexican Americans [4.5% (4.2%, 4.8%)] and non-Hispanic blacks [4.4% (4.1%, 4.7%)]. Estimated total iron absorption was 15.5% or 15.1%, depending on which approach was used to carry out the calculations. CONCLUSION: This study provides useful data for evaluating the current value of iron bioavailability from the US diet. PMID- 26377761 TI - High Amylose Starch with Low In Vitro Digestibility Stimulates Hindgut Fermentation and Has a Bifidogenic Effect in Weaned Pigs. AB - BACKGROUND: Dietary amylose resists enzymatic digestion, thereby providing a substrate for microbial fermentation that stimulates proliferation of beneficial microbiota and production of short-chain fatty acids (SCFAs) in the large intestine of pigs and humans. However, the effect of increasing dietary amylose in pigs immediately postweaning on growth, nutrient digestibility and flow, and intestinal microbial and SCFA profiles has not been studied and can be used as a model for newly weaned human infants. OBJECTIVE: We studied the effects of increasing dietary amylose on growth, nutrient digestibility, and intestinal microbial and metabolite profiles in weaned pigs. METHODS: Weaned pigs (n = 32) were randomly allocated to 1 of 4 diets containing 67% starch with 0%, 20%, 28%, or 63% amylose for 21 d. Subsequently, pigs were killed to collect feces and digesta for measuring starch digestion and microbial and metabolite profiles. RESULTS: Feeding weaned pigs 63% compared with 0%, 20%, and 28% amylose decreased (P < 0.05) feed intake by 5% and growth by >= 12%. Ileal digestibility of dry matter decreased (P < 0.05) by 10% and starch by 9%, thereby increasing (P < 0.05) hindgut fermentation, cecal and colonic total SCFAs, and colonic Bacteroides, and lowering (P < 0.01) ileal, cecal, and colonic pH in pigs consuming 63% compared with 0%, 20%, and 28% amylose. Cecal and colonic Bifidobacteria spp. increased by 14-30% (P < 0.05) and Clostridium clusters IV and XIVa were decreased (P < 0.01) in pigs consuming 63% compared with 0%, 20%, and 28% amylose. CONCLUSION: Increasing dietary amylose in pigs immediately postweaning stimulated hindgut fermentation and Bifidobacteria spp., thereby manipulating the gut environment, but also reduced intake and growth. An optimum dietary amylose concentration should be determined, which would maintain desired growth rate and gut environment in weaned pigs. PMID- 26377764 TI - Selectivity of a Singly Permeating Ion in Nonselective NaK Channel: Combined QM and MD Based Investigations. AB - Ion channels, such as potassium channels are known to discriminate ions to achieve remarkable selective transportation of K(+) over Na(+) through the membrane. The recently reported NaK ion channel, on the contrary, seems to be an exception, as it is observed to permeate most of the group IA alkali metal cations and hence is suggested to be nonselective in nature. However, does that correspond to a complete annihilation of selectivity inside the selectivity filter (SF) of the channel? What is the origin of such nonselectivity/selectivity, if any? The present computational study is an extensive multiscale modeling approach to find the probable answers to these intriguing questions. Here, we have used density functional theory (DFT) based calculations using a realistic truncated model of SF from the crystal structures of the NaK ion channel to evaluate the binding of various alkali metal ions (Na(+), K(+) and Cs(+)), free from "contamination" due to the absence any other "rivalry" cations, in its different binding sites. Among all of the possible binding sites, a vestibule is noticed to be nonselective and seen to act as a probable binding site only in the presence of multiple ions. Binding sites S3 and S4 are found to be selective for K(+) and Na(+), respectively. As an important observation, we find that calculations on oversimplified models using an isolated ion binding site may lead to an erroneous selectivity trend as it neglects the synergetics of consecutive binding sites on the final outcome. Energy decomposition analysis revealed ion-dipole electrostatics as the major contributing interaction in metal-bound binding sites. Our investigations find that although NaK is permeable to monovalent alkali metal ions, strongly "site specific" selectivity does exist at the three well-defined noncontiguous binding sites of the SF. Different important physicomechanical parameters (such as ligating environment, synergistic influence of binding sites, and topological constraints) are found to be the determining factor to induce the "site specific" selectivity of ions during translocation. Wherever possible, our computed results are compared with the available experimental findings. We finally conduct a detailed umbrella sampling-corrected metadynamics simulation in order to obtain an ion permeation free energy landscape within the SF that corroborates well with the "site specific" selectivity trend. PMID- 26377762 TI - Maternal Literacy, Facility Birth, and Education Are Positively Associated with Better Infant and Young Child Feeding Practices and Nutritional Status among Ugandan Children. AB - BACKGROUND: Understanding maternal factors that influence child feeding is necessary to inform intervention planning in settings in which mothers experience substantial social vulnerabilities. OBJECTIVE: The purpose of this study was to assess maternal sociodemographic factors that may constrain women's caring capabilities and subsequent child nutrition in Uganda. METHODS: We analyzed data from the 2006 and 2011 Uganda Demographic and Health Surveys to model the associations between maternal sociodemographic factors, child feeding practices, and anthropometry with multivariate logistic regression models. RESULTS: The proportion of children fed according to recommended guidelines declined in Uganda from 2006 to 2011. Mothers who lacked literacy skills were less likely to achieve recommended complementary feeding indicators; however, literacy was not associated with breastfeeding practices. Mothers in the upper 60% wealth percentile were more likely to meet minimum meal frequency, diversity, and adequacy indicators. Mothers who gave birth at health facilities (2006 OR: 0.49; 95% CI: 0.26, 0.91; P < 0.05) and who were in the upper 60% wealth percentile (2011 OR: 0.43; 95% CI: 0.21, 0.69) were less likely to exclusively breastfeed until 6 mo. There were no significant associations between age at first pregnancy, maternal education, and infant and young child feeding practices. Women with a formal education had children with lower stunting and underweight probabilities in both time periods (OR range: 0.43-0.74). Women who delivered in childbirth facilities were less likely to have a child with low weight-for-age, length-for-age, or weight-for-length z scores (OR range: 0.59-0.82). Marital status, the age at first child birth, not accepting domestic violence, freedom to travel away from home, and involvement in household and reproductive decisions were not associated with child anthropometry in either time period. CONCLUSIONS: Mothers with low literacy skills, who deliver their children at home, and who lack formal education are particularly at risk of poor child feeding and represent a group that may benefit from enhanced interventions that address their particular vulnerabilities. Factors that contribute to improved maternal feeding capabilities but may impair breastfeeding practices need to be better understood. PMID- 26377763 TI - A Comparison of Different Methods for Evaluating Diet, Physical Activity, and Long-Term Weight Gain in 3 Prospective Cohort Studies. AB - BACKGROUND: The insidious pace of long-term weight gain (~ 1 lb/y or 0.45 kg/y) makes it difficult to study in trials; long-term prospective cohorts provide crucial evidence on its key contributors. Most previous studies have evaluated how prevalent lifestyle habits relate to future weight gain rather than to lifestyle changes, which may be more temporally and physiologically relevant. OBJECTIVE: Our objective was to evaluate and compare different methodological approaches for investigating diet, physical activity (PA), and long-term weight gain. METHODS: In 3 prospective cohorts (total n = 117,992), we assessed how lifestyle relates to long-term weight change (up to 24 y of follow-up) in 4-y periods by comparing 3 analytic approaches: 1) prevalent diet and PA and 4-y weight change (prevalent analysis); 2) 4-y changes in diet and PA with a 4-y weight change (change analysis); and 3) 4-y change in diet and PA with weight change in the subsequent 4 y (lagged-change analysis). We compared these approaches and evaluated the consistency across cohorts, magnitudes of associations, and biological plausibility of findings. RESULTS: Across the 3 methods, consistent, robust, and biologically plausible associations were seen only for the change analysis. Results for prevalent or lagged-change analyses were less consistent across cohorts, smaller in magnitude, and biologically implausible. For example, for each serving of a sugar-sweetened beverage, the observed weight gain was 0.01 lb (95% CI: -0.08, 0.10) [0.005 kg (95% CI: -0.04, 0.05)] based on prevalent analysis; 0.99 lb (95% CI: 0.83, 1.16) [0.45 kg (95% CI: 0.38, 0.53)] based on change analysis; and 0.05 lb (95% CI: -0.10, 0.21) [0.02 kg (95% CI: -0.05, 0.10)] based on lagged-change analysis. Findings were similar for other foods and PA. CONCLUSIONS: Robust, consistent, and biologically plausible relations between lifestyle and long-term weight gain are seen when evaluating lifestyle changes and weight changes in discrete periods rather than in prevalent lifestyle or lagged changes. These findings inform the optimal methods for evaluating lifestyle and long-term weight gain and the potential for bias when other methods are used. PMID- 26377765 TI - The influence of reporting mode on children's cued personal memories. AB - The Autobiographical Memory Test (AMT) is widely used in research contexts to measure the extent to which participants (children or adults) report specific or general memories in response to cue words. Recalling fewer specific and more general memories (overgeneral memory) has been shown to be linked to depression in adults, but findings for youth, in particular, are mixed. Different versions of the AMT may be one contributing factor, yet this issue has received little research attention. The current study investigated the influence of reporting mode (written vs. spoken) on the specificity, length, and content of memories provided by 8- to 10-year-old children (N = 48). No significant differences were found in the number of specific responses given in the written and spoken modes. On the other hand, the spoken mode elicited longer and more detailed memories, although most content differences were eliminated when memory length was controlled. These findings suggest that different reporting modes can influence the nature of the memories reported, but the absolute differences are relatively small. PMID- 26377766 TI - Effect of Spinosad Resistance on Transmission of Tomato Spotted Wilt Virus by the Western Flower Thrips (Thysanoptera: Thripidae). AB - Tomato spotted wilt virus (TSWV) is transmitted by Frankliniella occidentalis (Pergande) in a persistent-propagative manner. We previously observed significant results in terms of feeding behavior of spinosad-susceptible (Ivf03) and resistant (Spin-R) strains of F. occidentalis using electrical penetration graph. TSWV transmission by the two strains was compared in the present study. The results showed that the titer of TSWV-N RNA (a part of S RNA of TSWV and encoding the nucleocapsid protein) in Ivf03 and Spin-R strains was not significantly different after a 48-h inoculation access period. The TSWV transmission rate did not significantly differ between the two strains and was 51.0% for Ivf03 and 44.4% for Spin-R. The virus transmission rate was significantly higher for males than females of both strains. The virus transmission rate for males and females of Ivf03 was 68.1 and 33.8%, respectively; however, in case of Spin-R, it was 60 and 28.8% for males and females, respectively. Additionally, number of probes and duration of probes were generally greater for viruliferous females of Ivf03 than for viruliferous females of Spin-R but the total number and duration of noningestion probes did not significantly differ between males of the two strains. The latter finding behavior may help explain the similar transmission rates for the susceptible and resistant strains. PMID- 26377767 TI - Collagen VI at a glance. AB - Collagen VI represents a remarkable extracellular matrix molecule, and in the past few years, studies of this molecule have revealed its involvement in a wide range of tissues and pathological conditions. In addition to its complex multi step pathway of biosynthesis and assembly that leads to the formation of a characteristic and distinctive network of beaded microfilaments in the extracellular matrix, collagen VI exerts several key roles in different tissues. These range from unique biomechanical roles to cytoprotective functions in different cells, including myofibers, chondrocytes, neurons, fibroblasts and cardiomyocytes. Indeed, collagen VI has been shown to exert a surprisingly broad range of cytoprotective effects, which include counteracting apoptosis and oxidative damage, favoring tumor growth and progression, regulating autophagy and cell differentiation, and even contributing to the maintenance of stemness. In this Cell Science at a Glance article and the accompanying poster, we present the current knowledge of collagen VI, and in particular, discuss its relevance in stemness and in preserving the mechanical properties of tissues, as well as its links with human disorders. PMID- 26377768 TI - [Glance at tropical dermatitis]. AB - We report a case of a French soldier, among more than fifteen others, who looked for dermatitis occurred in Central African Republic revealing a lepidopterism. We detail the Anaphae venata etiologic agent, what to do diagnosis and treatment. PMID- 26377769 TI - Distribution of Matrix Metalloproteinases in Human Atherosclerotic Carotid Plaques and Their Production by Smooth Muscle Cells and Macrophage Subsets. AB - PURPOSE: In this study, the potential of matrix metalloproteinase (MMP) sense for detection of atherosclerotic plaque instability was explored. Secondly, expression of MMPs by macrophage subtypes and smooth muscle cells (SMCs) was investigated. PROCEDURES: Twenty-three consecutive plaques removed during carotid endarterectomy were incubated in MMPSenseTM 680 and imaged with IVIS(r) Spectrum. mRNA levels of MMPs, macrophage markers, and SMCs were determined in plaque specimens, and in in vitro differentiated M1 and M2 macrophages. RESULTS: There was a significant difference between autofluorescence signals and MMPSense signals, both on the intraluminal and extraluminal sides of plaques. MMP-9 and CD68 messenger RNA (mRNA) expression was higher in hot spots, whereas MMP-2 and alphaSMA expression was higher in cold spots. In vitro M2 macrophages had higher mRNA expression of MMP-1, MMP-9, MMP-12, and TIMP-1 compared to M1 macrophages. CONCLUSION: MMP-9 is most dominantly MMP present in atherosclerotic plaques and is produced by M2 rather than M1 macrophages. PMID- 26377770 TI - Clinical, endoscopic, histological and radiological characteristics of Italian patients with eosinophilic oesophagitis. AB - BACKGROUND: Limited data are available on eosinophilic oesophagitis in Italy. AIM: To evaluate typical features of eosinophilic oesophagitis patients in a tertiary centre. METHODS: 973 consecutive patients with dysphagia and/or bolus impaction were prospectively enrolled and underwent upper endoscopy for eosinophilic oesophagitis (>=15 eosinophils in at least one high-power field [hpf] and no response to acid suppressants). Demographic and multiple clinical factors were collected. RESULTS: 45 patients (80% males, mean age 35+/-16) with incident eosinophilic oesophagitis (mean eosinophil peak count 57.2+/-40.6/hpf) were enrolled. 32 patients complained of solids dysphagia (71%), and 29 of bolus impaction (64%). Endoscopy found rings in 20 (44%), furrows in 9 (20%), whitish exudates/plaques in 12 (27%), crepe paper in 7 (13%) and normal findings in 14 patients (31%). Endoscopic and radiologic stenosis occurred in 20 (44%) and 23 (51%), respectively. Ten patients had proton pump inhibitor-oesophageal eosinophilia (22%). Topic fluticasone was effective in 28 of the remaining cases (62%), while 7 required additional treatments (16%). CONCLUSION: Eosinophilic oesophagitis prevalence was 12% in patients with dysphagia and/or bolus impaction, emphasizing the importance of this disease in Italy. Despite different environmental factors and dietary habits, Italian patients with eosinophilic oesophagitis present similar characteristics to those of other Western counties. PMID- 26377771 TI - Two-year prospective study of outcomes following total temporomandibular joint replacement. AB - The purpose of this 2-year prospective study was to investigate outcomes achieved with a stock temporomandibular joint (TMJ) replacement system in the management of end-stage TMJ disorders. Fifty-two patients requiring reconstruction (36 unilateral/16 bilateral) were operated on during the period 2006-2012; 68 total prostheses were implanted (Biomet Microfixation TMJ Replacement System). The mean age at surgery was 52.6+/-11.5 years. Changes in the values of inclusion diagnostic criteria at entry were assessed. These included persistent and significant TMJ pain, functional impairment after failure of other surgical therapies, and imaging evidence consistent with advanced TMJ disease of more than 1-year duration. Subjects were excluded if they presented insufficient quantity/quality of bone to support the TMJ replacement, severe hyperfunctional habits, active infectious disease, or an inability to follow postoperative instructions. Over the 2 years of postoperative follow-up, mean pain intensity was reduced from 6.4+/-1.4 to 1.6+/-1.2 (P<0.001), and jaw opening was improved from 2.7+/-0.9cm to 4.2+/-0.7cm (P<0.001). During the study period, three of 68 implants (4%) were explanted and new TMJ replacements fitted. The results of this study support the view that the surgical placement of stock TMJ prostheses provides significant long-term improvements in pain and function, with few complications. PMID- 26377772 TI - A decision tool for whole-body CT in major trauma that safely reduces unnecessary scanning and associated radiation risks: An initial exploratory analysis. AB - BACKGROUND: Whole-body CT (WBCT) has become routine practice in the assessment of major trauma patients. Whilst this may be associated with increased survival, several studies report high rates of negative scans. As no national guideline exists, selection criteria for WBCT vary widely. This study aims to (1) produce a scoring system that improves patient selection for WBCT (2) quantify patient radiation doses and their concomitant risk of malignancy. METHODS: Clinical notes were reviewed for all patients undergoing a WBCT for trauma over a 21-month period at a UK major trauma centre. Clinical and radiological findings were categorised according to body region. Univariate analysis was performed using Chi squared testing, followed by multivariable logistic regression. Secondary regression analysis of patients with significant injuries that the model did not identify was performed. The model was optimised and used to develop a scoring system. Sensitivity and specificity were calculated using the same dataset as was used to derive the models. Radiation exposure was determined and the excess lifetime risk of malignancy calculated. RESULTS: 255 patients were included, with a mean age of 45 years. 16% of scans were positive for polytrauma, 42% demonstrated some injury and 42% showed no injury. The regression model identified independent predictors of polytrauma to be (1) clinical signs in more than one body region, (2) reduced Glasgow Coma Score, (3) haemodynamic abnormality, (4) respiratory abnormality, (5) mechanism of injury. The final model had a sensitivity of 95% (95% CI 86-99%) and specificity of 59% (95% CI 52 66%) for significant CT findings. Mean radiation exposure was 31.8 mSv, conferring a median excess malignancy risk of 1 in 474. CONCLUSION: After including neurological deficit, our scoring system had a sensitivity of 97% (95% CI 88-99%) and specificity of 56% (95% CI 49-64%) for significant injury. We propose this is used to stratify the use of trauma radiographs, focused CT and WBCT for major trauma patients. Although not intended to replace clinical judgement, our scoring system adds an objective component to decision-making. We believe this will safely reduce the number of unnecessary CT scans performed on a relatively young cohort of patients. PMID- 26377773 TI - Predictors of mortality among initially stable adult pelvic trauma patients in the US: Data analysis from the National Trauma Data Bank. AB - OBJECTIVES: Pelvic fractures are associated with increased risk of death among trauma patients. Studies show independent risks predicting mortality among patients with pelvic fractures vary across different geographic regions. This study analyses national data to determine predictors of mortality in initially stable adult pelvic trauma patients in the US. METHODS: This study is a retrospective analysis of the US National Trauma Data Bank from January 2003 to December 2010 among trauma patients >=18 years of age with pelvic fractures (including acetabulum). Over 150 variables were reviewed and analysed. The primary outcome was all-cause in-hospital mortality. Logistic regression analysis was used to determine independent risk factors predictive of in-hospital mortality in stable pelvic fracture patients. RESULTS: 30,800 patients were included in the final analysis. Overall in-hospital mortality rate was 2.7%. Mortality increased twofold in middle aged patients (age 55-70), and increased nearly fourfold in patients with advanced age >=70. We found patients with advanced age, higher severity of injury, Glasgow Coma Scale (GCS) <8, GCS between 9 and 12, prolonged mechanical ventilation, and/or in-hospital blood product administration experienced higher mortality. Patients transported to level 1 or level 2 trauma centres experienced lower mortality while concomitantly experiencing higher associated internal injuries. CONCLUSIONS: Geriatric and middle aged pelvic fracture patients experience higher mortality. Predictors of mortality in initially stable pelvic fracture patients are advanced age, injury severity, mental status, prolonged mechanical ventilation, and/or in-hospital blood product administration. These patients might benefit from transport to local level 1 or level 2 trauma centres. PMID- 26377774 TI - Measuring the Absorption Rate of CO2 in Nonaqueous CO2-Binding Organic Liquid Solvents with a Wetted-Wall Apparatus. AB - The kinetics of the absorption of CO2 into two nonaqueous CO2-binding organic liquid (CO2 BOL) solvents were measured at T=35, 45, and 55 degrees C with a wetted-wall column. Selected CO2 loadings were run with a so-called "first generation" CO2 BOL, comprising an independent base and alcohol, and a "second generation" CO2 BOL, in which the base and alcohol were conjoined. Liquid-film mass-transfer coefficient (k'g ) values for both solvents were measured to be comparable to values for monoethanolamine and piperazine aqueous solvents under a comparable driving force, in spite of far higher solution viscosities. An inverse temperature dependence of the k'g value was also observed, which suggests that the physical solubility of CO2 in organic liquids may be making CO2 mass transfer faster than expected. Aspen Plus software was used to model the kinetic data and compare the CO2 absorption behavior of nonaqueous solvents with that of aqueous solvent platforms. This work continues our development of the CO2 BOL solvents. Previous work established the thermodynamic properties related to CO2 capture. The present paper quantitatively studies the kinetics of CO2 capture and develops a rate-based model. PMID- 26377775 TI - Detoxification of hexavalent chromium by Leucobacter sp. uses a reductase with specificity for dihydrolipoamide. AB - Leucobacter sp. belongs to the metal stressed community and possesses higher tolerance to metals including chromium and can detoxify toxic hexavalent chromium by reduction to less toxic trivalent chromium. But, the mechanism of reduction of hexavalent chromium by Leucobacter sp. has not been studied. Understanding the enzyme catalyzing reduction of chromium is important to improve the species for application in bioremediation. Hence, a soluble reductase catalyzing the reduction of hexavalent chromium was purified from a Leucobacter sp. and characterized. The pure chromate reductase was obtained from the cell-free extract through hydrophobic interaction and gel filtration column chromatographic methods. It was a monomeric enzyme and showed similar molecular weights in both gel filtration (~68 KDa) and SDS-PAGE (64 KDa). It reduced Cr(VI) using both NADH and NADPH as the electron donor, but exhibited higher activity with NADH. The optimal activity was found at pH 5.5 and 30 degrees C. The K(m) and V(max) for Cr(VI) reduction with NADH were 46.57 MUM and 0.37 MUmol min(-1) (mg protein) ( 1), respectively. The activity was inhibited by p-hydroxy mercury benzoate, Ag(2+) and Hg(2+) indicating the role of thiol groups in the catalysis. The spectrophotometric analysis of the purified enzyme showed the absence of bound flavin in the enzyme. The N-terminal amino acid sequence and LC/MS analysis of trypsin digested purified enzyme showed similarity to dihydrolipoyl dehydrogenase. The purified enzyme had dihydrolipoyl dehydrogenase activity with dihydrolipoamide as the substrate, which suggested that Leucobacter sp. uses reductase with multiple substrate specificity for reduction of Cr(VI) detoxification. PMID- 26377776 TI - Acute pathophysiological responses in the normal lungs of newborn piglets exposed to pure oxygen. AB - AIM: We investigated the effect of short-term pure oxygen treatment on pulmonary function, serum cytokine levels, and apoptosis in the lungs of healthy newborn piglets. METHODS: Twelve newborn piglets were randomly assigned to receive pure oxygen (OXY) (N.=6) or room air (AIR: 21% oxygen) (N.=6) for 4 hours. Cardiopulmonary function serum levels of interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF) alpha were evaluated. Histology was used to assess apoptosis and morphological differences between treatment groups. RESULTS: Four hour treatment with 100% oxygen resulted in higher PaO2, AaDO2, and compliance of the respiratory system (Crs) in the OXY than in the AIR animals. Serum levels of IL-6 were significantly higher in OXY piglets compared with AIR piglets (P=0.009), but there were no differences between groups in the serum levels of IL 1beta and TNF-alpha (P=0.640 and P=0.306, respectively). The piglets in the OXY group had a greater average number of apoptotic cells in the lung than AIR piglets, although this did not reach statistical significance. CONCLUSION: Our findings indicate that treatment with 100% oxygen for 4 hours may have clinical benefit by improving pulmonary function in normal neonates with limited increases in the inflammation and apoptosis. PMID- 26377777 TI - Attention deficit and hyperactivity disorder and infantile colic. AB - AIM: Attention deficit and hyperactivity disorder (ADHD) and infantile colic (IC) are heterogeneous diseases which's cause are unknown. Besides the different hypotheses in the etiology of both disorders maldevelopment in the metabolism of neurotransmitters in the central nervous system have been implicated. The goal of this study is to investigate the relationship between IC and ADHD due to possible common etiological factor as maldevelopment in neurochemical process. METHODS: A case-control study was carried out. The sample included 114 (77.2% male) children who were medically diagnosed with AD/HD and 149 (67.1% male) healthy children who were chosen from the same hospital's pediatric clinic as the control group. Parents and teachers completed the Conners Parent Rating Scale (CPRS), Conners Teacher Rating Scale (CTRS) and the patients were evaluated with The Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV). The parents were asked questions on a survey form filled out. IC was defined according to Wessel's modified criteria. RESULTS: The mean age of AD/HD group was 10.14+/-2.48 years and 9.94+/-2.34 years in the non-AD/HD group. The rate of IC in AD/HD and non-AD/HD groups were 50.0% and 30.2%, respectively and the difference was statistically significant between two groups (P=0.001). Duration of IC was similar in the groups (P=143). CONCLUSION: IC may be a postnatal risk factor and marker for AD/HD during childhood. Both diseases may have a common mechanism. Such infants need to be examined and followed up more intensively. PMID- 26377778 TI - Analysis of risk factors for hydrocephalus development in newborn infants with germinal matrix hemorrhage. AB - AIM: The aim of this study was to analyze risk factors for the development of hydrocephalus in newborn infants with germinal matrix (GM) hemorrhage. METHODS: The study comprised 271 patients admitted to Carlos Haya University Hospital in Malaga with GM hemorrhage. The following data were recorded: gestational age, gender, twin birth, head circumference at birth, weight at birth, and Papile grade. Severe obstetrical (abruption, chorioamnionitis, pregnancy-induced hypertension, tocolytic treatment) and neonatal disorders (respiratory distress syndrome, neonatal infection, coagulation disorder, patent ductus arteriosus, necrotizing enterocolitis) were also recorded. Symptomatic hydrocephalus was diagnosed in the event of a progressive increase in head circumference and ventricular indices requiring shunting. RESULTS: Of the 271 patients, 139 (51%) developed posthemorrhagic ventriculomegaly; 47 patients (17%) developed symptomatic hydrocephalus and needed shunt implantation. We found a significant relationship between the development of symptomatic hydrocephalus and Papile grade, lower gestational age, lower birth weight, twin birth, and neonatal infection. CONCLUSION: Awareness of risk factors for the development of hydrocephalus in newborn infants with GM hemorrhage should be emphasized in order to enable an early diagnosis of ventriculomegaly and symptomatic hydrocephalus and thus make a correct therapeutic decision. PMID- 26377779 TI - Sequencing of the CFTR gene in selected Turkish patients with cystic fibrosis. AB - AIM: Common mutation detection panels are usually used in clinical practice in most of the centers of our country in order to demonstrate mutations of cystic fibrosis (CF) patients. But heterogenicity of CFTR mutations in Turkey makes identification of CFTR mutations extremely difficult while using common mutation detection panels. METHODS: In this report, we described our experience and findings in offering sequencing of the CFTR gene to 17 patients in which no mutations were identified by common mutation analysis. RESULTS: Overall allele informativity increased from 4/34 (11.76%) to 13/34 (38.2%) after whole exon sequencing of CFTR in our patients. CONCLUSION: Genotype of CF patients could be entirely described in some of our patients by CFTR sequencing but there is still a group of patients, independently from their clinical classification whose mutations can not be determined by CFTR sequencing. PMID- 26377780 TI - Evaluation of the intraocular pressure in obese adolescents. AB - AIM: The aim of this study was to evaluate the intraocular pressure (IOP) levels of children with normal and high Body Mass Index (BMI) and to find out the potential correlation between glaucoma and obesity. METHODS: Thirty obese and thirty healty children were enrolled in this study. Physical examinations and anthropometric measurements of all patients and controls were performed. Obesity was defined as a BMI exceeding the 95th percentile for the patients according to age and sex. All participants were underwent a complete eye examination. The results of these measurements were considered for statistical analysis. RESULTS: Mean age was 13.5+/-2.1 years in obese group and 13.3+/-2.0 years in control group. Mean BMIs were 28.1+/-3.9 kg/m2 and 19.7+/-1.2 kg/m2 in obese and control groups, respectively. No significant difference was found in mean IOP levels of both right and left eyes between two groups (P=0.837 and P=0.755, respectively). There was no significant difference in cup/disc ratios of each eyes and mean central corneal thickness of both right and left eyes between obese patients and controls. In visual field analysis, no statistically significant difference in mean false negativeness and mean false positiveness were found between two groups. There were not also any significant correlations in both mean deviation of each eyes (P=0.78 and P=0.94, respectively) and pattern standart deviation of right and left eyes (P=0.89 and P=0.90, respectively) between obese cases and controls. CONCLUSION: In this study, there were no significant difference in IOP measurements, central corneal thicknesses, cup/disc ratios and visual field parameters between obese and normal children. No significant correlation was found between obesity and glaucoma or elevated IOP in children. PMID- 26377781 TI - Bone mineralization defects after treatment of acute lymphoblastic leukemia in children. AB - AIM: Aim of the study was to assess bone metabolism disturbances in children with acute lymphoblastic leukemia following cessation of chemotherapy. For this purpose we measured bone mineral density (BMD) and evaluated bone metabolism markers. METHODS: Seventy-five patients (37 female, 38 males, mean age 10.77+/ 3.80 years) were included. Lumbar spine BMD was measured by dual energy X-ray absorptiometry and serum calcium, phosphorus, magnesium, alkaline phosphatase, parathyroid hormone and 25OH vitamin D levels were analyzed. For characteristics of all patients at diagnosis data were retreived from hospital records and analyzed retrospectively. RESULTS: A total of 18.66% (14 patients) of patients were osteoporotic (z score <-2 SD), 22.67% (17 patients) were osteopenic (z-score between -2 and -1 SD) and 58.67% (44 patients) presented normal z-scores (>-1 SD). There were no statisticaly significant differences between normal, osteopenic and osteoporotic groups for mean serum vitamine D (P=0.677), calcium (P=0.280), phosphorus (P=0.179), magnesium (P=0.675), ALP (P=0.092) and serum PTH (P=0.915) levels. According to ages (P=0.745) and gender (P=0.810) there were no significant differences in BMD. There were no significant differences between normal, osteopenic and osteoporotic patients for the total dose of prednisolone (P=0.334), dexamethasone, (P=0.734), methotrexate (P=0.911), granulocyte colony stimulating factor (P=0.173) and cranial irradiation (P=0.912) they have received during chemotherapy. Bone fracture and aseptic necrosis rates were 12%, 8%, respectively. CONCLUSION: Osteoporosis and osteopenia are still observed in high rates after chemotherapy. We must be aware of this morbidity and must screen the patients for decreased BMD during the long duration of leukemia treatment. Supportive treatments should be evaluated to minimize these serious complications. PMID- 26377783 TI - [The top twelve most important discoveries made by Italian pediatric researchers]. PMID- 26377782 TI - Impact of attention-deficit/hyperactivity disorder on the lives of Italian children and adolescents: data from the European Lifetime Impairment Survey. AB - AIM: In Italy, attention-deficit/hyperactivity disorder (ADHD) remains under diagnosed. The Lifetime Impairment Survey assessed impairments/symptoms of ADHD in children across six European countries. Results relating to the Italian sample are discussed here. METHODS: Parents/caregivers of children aged <20 years with ADHD (ADHD group) and without ADHD (control group) were invited to participate in an online survey. Participants answered questions relating to their eldest/only child. History of ADHD diagnosis was self-reported. Eight impairment and symptom scales and two summed scores were created to compare the ADHD and control groups; higher scores indicate greater impairment. RESULTS: In Italy, 104 parents/caregivers of children with ADHD and 105 parents/caregivers of children without ADHD participated in the survey (N.=83 and N.=84, respectively, after exclusion of participants with implausible answers). The ADHD group had higher mean (standard deviation) scores than the control group for home impairment (2.1 [0.5]) vs. 1.9 [0.4]; P<0.001), school impairment (2.8 [0.6] vs. 2.1 [0.6]; P<0.001), relationship impairment (2.3 [0.8] vs. 1.9 [0.7]; P<0.001) and comorbid symptoms (3.3 [0.7] vs. 2.5 [0.7]; P<0.001). Impairment at home and at school were correlated with each other (r=0.478; P<0.001) and with ADHD symptoms (r=0.321; P<0.001 and r=0.462; P<0.001, respectively), comorbid symptoms (r=0.231; P<0.05 and r=0.420; P<0.001), school failure (r=0.208; P<0.02 and r=0.320; P<0.001) and relationship impairments (r=0.432; P<0.01 and r=0.645; P<0.001). CONCLUSION: The daily lives of children with ADHD in Italy are significantly affected by impairments associated with ADHD. Children and adolescents with ADHD in Italy should receive prompt diagnosis and appropriate therapy. PMID- 26377784 TI - Maternal vitamin D deficiency as a cause of hypocalcemic convulsions in a newborn from foreign parents: a re-emerging public health issue in Western countries? PMID- 26377785 TI - In the era of "red nose", can clown-therapy reduce the nursing staff's anxiety? PMID- 26377786 TI - Rectal duplication cyst in previous anorectal malformation and Down syndrome. PMID- 26377787 TI - Biomolecular Systems Interactions, Dynamics, and Allostery: Reflections and New Directions. PMID- 26377789 TI - MATWIN: bridging the gap between academic research and industry. AB - MATWIN (Maturation and Accelerating Translation With INdustry) is part of the nationwide effort to support cancer innovation. This unique program is willing to support innovative research projects providing tools, resources, and staff dedicated to project leaders wishing to optimize the industrial attractiveness of their project. The overall objective is clear: fight cancer always more effectively. PMID- 26377788 TI - Contractile function assessment by intraventricular balloon alters the ability of regional ischaemia to evoke ventricular fibrillation. AB - BACKGROUND AND PURPOSE: In drug research using the rat Langendorff heart preparation, it is possible to study left ventricular (LV) contractility using an intraventricular balloon (IVB), and arrhythmogenesis during coronary ligation induced regional ischaemia. Assessing both concurrently would halve animal requirements. We aimed to test the validity of this approach. EXPERIMENTAL APPROACH: The electrocardiogram (ECG) and LV function (IVB) were recorded during regional ischaemia of different extents in a randomized and blinded study. KEY RESULTS: IVB-induced proarrhythmia was anticipated, but in hearts with an ischaemic zone (IZ) made deliberately small, an inflated IVB reduced ischaemia induced ventricular fibrillation (VF) incidence as a trend. Repeating studies in hearts with large IZs revealed the effect to be significant. There were no changes in QT interval or other variables that might explain the effect. Insertion of an IVB that was minimally inflated had no effect on any variable compared with 'no IVB' controls. The antiarrhythmic effect of verapamil (a positive control drug) was unaffected by IVB inflation. Removal of an inflated (but not a non-inflated) IVB caused a release of lactate commensurate with reperfusion of an endocardial/subendocardial layer of IVB-induced ischaemia. This was confirmed by intracellular (31) phosphorus ((31) P) nuclear magnetic resonance (NMR) spectroscopy. CONCLUSIONS AND IMPLICATIONS: IVB inflation does not inhibit VF suppression by a standard drug, but it has profound antiarrhythmic effects of its own, likely to be due to inflation-induced localized ischaemia. This means rhythm and contractility cannot be assessed concurrently by this approach, with implications for drug discovery and safety assessment. PMID- 26377790 TI - Successful treatment of recurrent preoperative bleeding of glioblastoma with recombinant activated factor VII: pathophysiological hypothesis. PMID- 26377792 TI - Human organic anion transporter 2 is distinct from organic anion transporters 1 and 3 with respect to transport function. AB - Phylogentically, organic anion transporter (OAT)1 and OAT3 are closely related, whereas OAT2 is more distant. Experiments with human embryonic kidney-293 cells stably transfected with human OAT1, OAT2, or OAT3 were performed to compare selected transport properties. Common to OAT1, OAT2, and OAT3 is their ability to transport cGMP. OAT2 interacted with prostaglandins, and cGMP uptake was inhibited by PGE2 and PGF2alpha with IC50 values of 40.8 and 12.7 MUM, respectively. OAT1 (IC50: 23.7 MUM), OAT2 (IC50: 9.5 MUM), and OAT3 (IC50: 1.6 MUM) were potently inhibited by MK571, an established multidrug resistance protein inhibitor. OAT2-mediated cGMP uptake was not inhibited by short-chain monocarboxylates and, as opposed to OAT1 and OAT3, not by dicarboxylates. Consequently, OAT2 showed no cGMP/glutarate exchange. OAT1 and OAT3 exhibited a pH and a Cl- dependence with higher substrate uptake at acidic pH and lower substrate uptake in the absence of Cl-, respectively. Such pH and Cl- dependencies were not observed with OAT2. Depolarization of membrane potential by high K+ concentrations in the presence of the K+ ionophore valinomycin left cGMP uptake unaffected. In addition to cGMP, OAT2 transported urate and glutamate, but cGMP/glutamate exchange could not be demonstrated. These experiments suggest that OAT2-mediated cGMP uptake does not occur via exchange with monocarboxylates, dicarboxylates, and hydroxyl ions. The counter anion for electroneutral cGMP uptake remains to be identified. PMID- 26377791 TI - PPREMO: a prospective cohort study of preterm infant brain structure and function to predict neurodevelopmental outcome. AB - BACKGROUND: More than 50 percent of all infants born very preterm will experience significant motor and cognitive impairment. Provision of early intervention is dependent upon accurate, early identification of infants at risk of adverse outcomes. Magnetic resonance imaging at term equivalent age combined with General Movements assessment at 12 weeks corrected age is currently the most accurate method for early prediction of cerebral palsy at 12 months corrected age. To date no studies have compared the use of earlier magnetic resonance imaging combined with neuromotor and neurobehavioural assessments (at 30 weeks postmenstrual age) to predict later motor and neurodevelopmental outcomes including cerebral palsy (at 12-24 months corrected age). This study aims to investigate i) the relationship between earlier brain imaging and neuromotor/neurobehavioural assessments at 30 and 40 weeks postmenstrual age, and ii) their ability to predict motor and neurodevelopmental outcomes at 3 and 12 months corrected age. METHODS/DESIGN: This prospective cohort study will recruit 80 preterm infants born <= 30 week's gestation and a reference group of 20 healthy term born infants from the Royal Brisbane & Women's Hospital in Brisbane, Australia. Infants will undergo brain magnetic resonance imaging at approximately 30 and 40 weeks postmenstrual age to develop our understanding of very early brain structure at 30 weeks and maturation that occurs between 30 and 40 weeks postmenstrual age. A combination of neurological (Hammersmith Neonatal Neurologic Examination), neuromotor (General Movements, Test of Infant Motor Performance), neurobehavioural (NICU Network Neurobehavioural Scale, Premie-Neuro) and visual assessments will be performed at 30 and 40 weeks postmenstrual age to improve our understanding of the relationship between brain structure and function. These data will be compared to motor assessments at 12 weeks corrected age and motor and neurodevelopmental outcomes at 12 months corrected age (neurological assessment by paediatrician, Bayley scales of Infant and Toddler Development, Alberta Infant Motor Scale, Neurosensory Motor Developmental Assessment) to differentiate atypical development (including cerebral palsy and/or motor delay). DISCUSSION: Earlier identification of those very preterm infants at risk of adverse neurodevelopmental and motor outcomes provides an additional period for intervention to optimise outcomes. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12613000280707. Registered 8 March 2013. PMID- 26377793 TI - Transcriptional regulation of NHE3 and SGLT1 by the circadian clock protein Per1 in proximal tubule cells. AB - We have previously demonstrated that the circadian clock protein period (Per)1 coordinately regulates multiple genes involved in Na(+) reabsorption in renal collecting duct cells. Consistent with these results, Per1 knockout mice exhibit dramatically lower blood pressure than wild-type mice. The proximal tubule is responsible for a majority of Na(+) reabsorption. Previous work has demonstrated that expression of Na(+)/H(+) exchanger 3 (NHE3) oscillates with a circadian pattern and Na(+)-glucose cotransporter (SGLT)1 has been demonstrated to be a circadian target in the colon, but whether these target genes are regulated by Per1 has not been investigated in the kidney. The goal of the present study was to determine if Per1 regulates the expression of NHE3, SGLT1, and SGLT2 in the kidney. Pharmacological blockade of nuclear Per1 entry resulted in decreased mRNA expression of SGLT1 and NHE3 but not SGLT2 in the renal cortex of mice. Per1 small interfering RNA and pharmacological blockade of Per1 nuclear entry in human proximal tubule HK-2 cells yielded the same results. Examination of heterogeneous nuclear RNA suggested that the effects of Per1 on NHE3 and SGLT1 expression occurred at the level of transcription. Per1 and the circadian protein CLOCK were detected at promoters of NHE3 and SGLT1. Importantly, both membrane and intracellular protein levels of NHE3 and SGLT1 were decreased after blockade of nuclear Per1 entry. This effect was associated with reduced activity of Na(+) K(+)-ATPase. These data demonstrate a role for Per1 in the transcriptional regulation of NHE3 and SGLT1 in the kidney. PMID- 26377795 TI - Double transduction of a Cre/LoxP lentiviral vector: a simple method to generate kidney cell-specific knockdown mice. AB - In a lentivirus-based gene delivery system, the incorporated gene is continuously expressed for a long time. In this study, we devised a simple way to knock down a specific gene in a kidney cell-specific pattern in adult mice by lentivirus assisted transfer of short hairpin RNA (shRNA). Kidney collecting duct (CD) specific aquaporin-3 (AQP3)-knockdown mice were generated by consecutive injection of Hoxb7-Cre-expressing lentivirus (LV-Hoxb7 Cre) and loxP-AQP3 shRNA expressing lentivirus (LV-loxP shAQP3) in adult C57BL6/J mice. LV-Hoxb7 Cre was designed to express mCherry, while LV-loxP shAQP3 was designed with a floxed enhanced green fluorescent protein (EGFP)-tagged stop sequence, and thus EGFP would be expressed only in the absence of Cre recombination. In mice treated with LV-Hoxb7 Cre alone, mCherry protein expression, which indicates the presence of Cre recombinase, occurred only in CD cells. However, LV-loxP shAQP3 injection alone resulted in an increase in EGFP expression in all kidney cells, indicating the transcription of the floxed region. When LV-Hoxb7 Cre and LV-loxP shAQP3 were sequentially transduced, EGFP expression was attenuated while mCherry expression was sustained in CD cells, demonstrating a CD cell-specific recombination of the floxed region. AQP3 expression in mice injected with LV-Hoxb7 Cre or LV-loxP shAQP3 alone did not differ, but consecutive injection of LV-Hoxb7 Cre and LV loxP shAQP3 significantly reduced AQP3 expression in CD cells. However, the expression levels of AQP3 were not altered in other cell types. Double transduction of Cre- and loxP-based lentivirus can easily generate kidney cell specific knockdown mice, and this method might be applicable to other species. PMID- 26377794 TI - Role of FQQI motif in the internalization, trafficking, and signaling of guanylyl cyclase/natriuretic peptide receptor-A in cultured murine mesangial cells. AB - Binding of the cardiac hormone atrial natriuretic peptide (ANP) to transmembrane guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA), produces the intracellular second messenger cGMP in target cells. To delineate the critical role of an endocytic signal in intracellular sorting of the receptor, we have identified a FQQI (Phe(790), Gln(791), Gln(792), and Ile(793)) motif in the carboxyl-terminal region of NPRA. Mouse mesangial cells (MMCs) were transiently transfected with the enhanced green fluorescence protein (eGFP)-tagged wild-type (WT) and mutant constructs of eGFP-NPRA. The mutation FQQI/AAAA, in the eGFP-NPRA cDNA sequence, markedly attenuated the internalization of mutant receptors by almost 49% compared with the WT receptor. Interestingly, we show that the MU1B subunit of adaptor protein-1 binds directly to a phenylalanine-based FQQI motif in the cytoplasmic tail of the receptor. However, subcellular trafficking indicated that immunofluorescence colocalization of the mutated receptor with early endosome antigen-1 (EEA-1), lysosome-associated membrane protein-1 (LAMP 1), and Rab 11 marker was decreased by 57% in early endosomes, 48% in lysosomes, and 42% in recycling endosomes, respectively, compared with the WT receptor in MMCs. The receptor containing the mutated motif (FQQI/AAAA) also produced a significantly decreased level of intracellular cGMP during subcellular trafficking than the WT receptor. The coimmunoprecipitation assay confirmed a decreased level of colocalization of the mutant receptor with subcellular compartments during endocytic processes. The results suggest that the FQQI motif is essential for the internalization and subcellular trafficking of NPRA during the hormone signaling process in intact MMCs. PMID- 26377796 TI - Being dedicated. PMID- 26377797 TI - Reciprocal effect of angiotensin II in collecting duct renin synthesis. PMID- 26377798 TI - Knockdown of Tmem234 in zebrafish results in proteinuria. AB - Podocytes are highly specialized epithelial cells located at the outer aspects of the glomerular capillary tuft and critical components of the kidney filtration barrier. To maintain their unique features, podocytes express a number of proteins that are only sparsely found elsewhere in the body. In this study, we have identified four (Tmem234, Znf185, Lrrc49, and Slfn5) new highly podocyte enriched proteins. The proteins are strongly expressed by podocytes, while other parts of the kidney show only weak or no expression. Tmem234, Slfn5, and Lrrc49 are located in foot processes, whereas Znf185 is found in both foot and major processes. Expressional studies in developing kidneys show that these proteins are first expressed at the capillary stage glomerulus, the same stage when the formation of major and foot processes begins. We identified zebrafish orthologs for Tmem234 and Znf185 genes and knocked down their expression using morpholino technology. Studies in zebrafish larvae indicate that Tmem234 is essential for the organization and functional integrity of the pronephric glomerulus filtration barrier, as inactivation of Tmem234 expression results in foot process effacement and proteinuria. In summary, we have identified four novel highly podocyte enriched proteins and show that one of them, Tmem234, is essential for the normal filtration barrier in the zebrafish pronephric glomerulus. Identification of new molecular components of the kidney filtration barrier opens up possibilities to study their role in glomerulus biology and diseases. PMID- 26377799 TI - Site Targeted Press Coated Delivery of Methylprednisolone Using Eudragit RS 100 and Chitosan for Treatment of Colitis. AB - BACKGROUND: Inflammatory bowel disease (IBD) is one of the five most prevalent gastrointestinal disease burdens which commonly require lifetime care. Worldwide incidence rate of ulcerative colitis and Crohn's disease is about 16.8% and 13.4% respectively. Colitis is an inflammation of the colon. Colon targeted drug delivery will direct the drug to the colon. The drug will reach at the site of action and hence its side effects as well as dose can be reduced. Recent patent describes treatment of ulcerative colitis using anti CD3 antibodies, with nicotine and anti-depressant drugs, budesonide foam etc. OBJECTIVE: Present study deals with optimization of site targeted methylprednisolone delivery for treatment of colitis. METHOD: Chitosan and Eudragit RS 100 were used as coating polymers. Tablets were prepared by press coated technology. The core tablets contain drug, avicel as binder, croscarmellose sodium as super disintegrant and dicalcium phosphate as diluent. Drug excipient compatibility was carried out using FTIR, UV and DSC. Design of experiment was used to optimize the formulation. Tablets were evaluated for thickness, weight variation, hardness, swelling index, in-vitro drug release and release of drug in simulated media. RESULTS: Optimized batch (B2) contained chitosan 40% and eudragit RS 100 17.5%. B2 showed in-vitro drug release 85.65 +/- 7.6% in 6.8 pH phosphate buffer and 96.7 +/-9.1% in simulated media after 7.5 hours. CONCLUSION: In-vivo x-ray placebo study for formulation B2 had shown that the tablet reached to the ascending colon after 5 hours. This indicated a potential site targeted delivery of optimized batch B2. PMID- 26377800 TI - The crystal structure of JNK from Drosophila melanogaster reveals an evolutionarily conserved topology with that of mammalian JNK proteins. AB - BACKGROUND: The c-Jun N-terminal kinases (JNKs), members of the mitogen-activated protein kinase (MAPK) family, engage in diverse cellular responses to signals produced under normal development and stress conditions. In Drosophila, only one JNK member is present, whereas ten isoforms from three JNK genes (JNK1, 2, and 3) are present in mammalian cells. To date, several mammalian JNK structures have been determined, however, there has been no report of any insect JNK structure. RESULTS: We report the first structure of JNK from Drosophila melanogaster (DJNK). The crystal structure of the unphosphorylated form of DJNK complexed with adenylyl imidodiphosphate (AMP-PNP) has been solved at 1.79 A resolution. The fold and topology of DJNK are similar to those of mammalian JNK isoforms, demonstrating their evolutionarily conserved structures and functions. Structural comparisons of DJNK and the closely related mammalian JNKs also allow identification of putative catalytic residues, substrate-binding sites and conformational alterations upon docking interaction with Drosophila scaffold proteins. CONCLUSIONS: The DJNK structure reveals common features with those of the mammalian JNK isoforms, thereby allowing the mapping of putative catalytic and substrate binding sites. Additionally, structural changes upon peptide binding could be predicted based on the comparison with the closely-related JNK3 structure in complex with pepJIP1. This is the first structure of insect JNK reported to date, and will provide a platform for future mutational studies in Drosophila to ascertain the functional role of insect JNK. PMID- 26377801 TI - Elevated growth temperature decreases levels of the PEX5 peroxisome-targeting signal receptor and ameliorates defects of Arabidopsis mutants with an impaired PEX4 ubiquitin-conjugating enzyme. AB - BACKGROUND: Peroxisomes house critical metabolic reactions. For example, fatty acid beta-oxidation enzymes, which are essential during early seedling development, are peroxisomal. Peroxins (PEX proteins) are needed to bring proteins into peroxisomes. Most matrix proteins are delivered to peroxisomes by PEX5, a receptor that forms transient pores to escort proteins across the peroxisomal membrane. After cargo delivery, a peroxisome-tethered ubiquitin conjugating enzyme (PEX4) and peroxisomal ubiquitin-protein ligases mono- or polyubiquitinate PEX5 for recycling back to the cytosol or for degradation, respectively. Arabidopsis pex mutants beta-oxidize fatty acids inefficiently and therefore fail to germinate or grow less vigorously. These defects can be partially alleviated by providing a fixed carbon source, such as sucrose, in the growth medium. Despite extensive characterization of peroxisome biogenesis in Arabidopsis grown in non-challenged conditions, the effects of environmental stressors on peroxisome function and pex mutant dysfunction are largely unexplored. RESULTS: We surveyed the impact of growth temperature on a panel of pex mutants and found that elevated temperature ameliorated dependence on external sucrose and reduced PEX5 levels in the pex4-1 mutant. Conversely, growth at low temperature exacerbated pex4-1 physiological defects and increased PEX5 levels. Overexpressing PEX5 also worsened pex4-1 defects, implying that PEX5 lingering on the peroxisomal membrane when recycling is impaired impedes peroxisome function. Growth at elevated temperature did not reduce the fraction of membrane-associated PEX5 in pex4-1, suggesting that elevated temperature did not restore PEX4 enzymatic function in the mutant. Moreover, preventing autophagy in pex4-1 did not restore PEX5 levels at high temperature. In contrast, MG132 treatment increased PEX5 levels, implicating the proteasome in degrading PEX5, especially at high temperature. CONCLUSIONS: We conclude that growth at elevated temperature increases proteasomal degradation of PEX5 to reduce overall PEX5 levels and ameliorate pex4-1 physiological defects. Our results support the hypothesis that efficient retrotranslocation of PEX5 after cargo delivery is needed not only to make PEX5 available for further rounds of cargo delivery, but also to prevent the peroxisome dysfunction that results from PEX5 lingering in the peroxisomal membrane. PMID- 26377802 TI - Inhibition of NOX2 reduces locomotor impairment, inflammation, and oxidative stress after spinal cord injury. AB - BACKGROUND: Spinal cord injury (SCI) results in the activation of the NADPH oxidase (NOX) enzyme, inducing production of reactive oxygen species (ROS). We hypothesized that the NOX2 isoform plays an integral role in post-SCI inflammation and functional deficits. METHODS: Moderate spinal cord contusion injury was performed in adult male mice, and flow cytometry, western blot, and immunohistochemistry were used to assess NOX2 activity and expression, inflammation, and M1/M2 microglia/macrophage polarization from 1 to 28 days after injury. The NOX2-specific inhibitor, gp91ds-tat, was injected into the intrathecal space immediately after impact. The Basso Mouse Scale (BMS) was used to assess locomotor function at 24 h post-injury and weekly thereafter. RESULTS: Our findings show that gp91ds-tat treatment significantly improved functional recovery through 28 days post-injury and reduced inflammatory cell concentrations in the injured spinal cord at 24 h and 7 days post-injury. In addition, a number of oxidative stress markers were reduced in expression at 24 h after gp91ds-tat treatment, which was accompanied by a reduction in M1 polarization marker expression. CONCLUSION: Based on our findings, we now conclude that inhibition of NOX2 significantly improves outcome after SCI, most likely via acute reductions in oxidative stress and inflammation. NOX2 inhibition may therefore have true potential as a therapy after SCI. PMID- 26377803 TI - Objectively measured physical activity and sedentary time in youth: the International children's accelerometry database (ICAD). AB - BACKGROUND: Physical activity and sedentary behaviour in youth have been reported to vary by sex, age, weight status and country. However, supporting data are often self-reported and/or do not encompass a wide range of ages or geographical locations. This study aimed to describe objectively-measured physical activity and sedentary time patterns in youth. METHODS: The International Children's Accelerometry Database (ICAD) consists of ActiGraph accelerometer data from 20 studies in ten countries, processed using common data reduction procedures. Analyses were conducted on 27,637 participants (2.8-18.4 years) who provided at least three days of valid accelerometer data. Linear regression was used to examine associations between age, sex, weight status, country and physical activity outcomes. RESULTS: Boys were less sedentary and more active than girls at all ages. After 5 years of age there was an average cross-sectional decrease of 4.2% in total physical activity with each additional year of age, due mainly to lower levels of light-intensity physical activity and greater time spent sedentary. Physical activity did not differ by weight status in the youngest children, but from age seven onwards, overweight/obese participants were less active than their normal weight counterparts. Physical activity varied between samples from different countries, with a 15-20% difference between the highest and lowest countries at age 9-10 and a 26-28% difference at age 12-13. CONCLUSIONS: Physical activity differed between samples from different countries, but the associations between demographic characteristics and physical activity were consistently observed. Further research is needed to explore environmental and sociocultural explanations for these differences. PMID- 26377805 TI - The Italian Version of the Tilburg Frailty Indicator: Analysis of Psychometric Properties. AB - This study aims to assess the reliability, construct validity (convergent/divergent), and criterion validity of the Italian version of the Tilburg Frailty Indicator (TFI). The TFI is a self-report questionnaire for screening frailty in older adults. Two hundred and sixty-seven community-dwelling older adults were involved. Psychometric properties were analyzed using validated instruments. Adverse outcomes such as disability, falls, and visits to a general practitioner were detected. Participants were mainly women (59.9%), with a mean age of 73.4 years (SD = 6.0). Internal consistency reliability was acceptable. Construct validity was good, since each item of the TFI correlated as expected with corresponding frailty measures. Convergent and divergent validity were adequate for all the domains of the TFI. Criterion validity was excellent for disability and mediocre for the other two outcomes. This study supports the validity of the Italian TFI and offers to clinicians and scientists a multidimensional instrument for identifying frail individuals in the Italian context. PMID- 26377806 TI - [In Process Citation]. PMID- 26377804 TI - Genetic influences on the neural and physiological bases of acute threat: A research domain criteria (RDoC) perspective. AB - The NIMH Research Domain Criteria (RDoC) initiative aims to describe key dimensional constructs underlying mental function across multiple units of analysis-from genes to observable behaviors-in order to better understand psychopathology. The acute threat ("fear") construct of the RDoC Negative Valence System has been studied extensively from a translational perspective, and is highly pertinent to numerous psychiatric conditions, including anxiety and trauma related disorders. We examined genetic contributions to the construct of acute threat at two units of analysis within the RDoC framework: (1) neural circuits and (2) physiology. Specifically, we focused on genetic influences on activation patterns of frontolimbic neural circuitry and on startle, skin conductance, and heart rate responses. Research on the heritability of activation in threat related frontolimbic neural circuitry is lacking, but physiological indicators of acute threat have been found to be moderately heritable (35-50%). Genetic studies of the neural circuitry and physiology of acute threat have almost exclusively relied on the candidate gene method and, as in the broader psychiatric genetics literature, most findings have failed to replicate. The most robust support has been demonstrated for associations between variation in the serotonin transporter (SLC6A4) and catechol-O-methyltransferase (COMT) genes with threat-related neural activation and physiological responses. However, unbiased genome-wide approaches using very large samples are needed for gene discovery, and these can be accomplished with collaborative consortium-based research efforts, such as those of the Psychiatric Genomics Consortium (PGC) and Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Consortium. PMID- 26377807 TI - [Thrombosis and post-thrombotic syndrome as a consequence of an accident]. AB - Phlebothromboses represent alarming complications in accident victims since they can cause fatal pulmonary embolisms. More than half of those affected also develop post-thrombotic syndrome in the course of the illness. In addition to making clinical assessments, the traumatologist should also have fundamental knowledge about diagnostic methods and be familiar with interpreting internal findings. Colour-coded duplex sonography plays a central role in diagnosing thrombosis and in assessing functional limitations. Further information can be gathered from various phlebological procedures. The expert evaluation of the immediate, as well as the long-term consequences of an accident frequently require leg swelling to be classified. It is not uncommon for post-thrombotic syndrome to be diagnosed for the first time during this process. An additional vascular appraisal is often required. An appreciation of social-medical and insurance-related aspects means a high degree of responsibility is placed on the expert. PMID- 26377808 TI - Recommendations for resistance training in patients with fibromyalgia. AB - It may seem counter-intuitive to purposely stress muscle in patients who have muscle pain. However, a growing body of evidence challenges the assumption that resistance (strength) training worsens muscle pain in people with fibromyalgia (FM). In fact, the latest evidence indicates that when resistance training is tailored to individual needs, people with FM can obtain worthwhile improvements in FM severity. Clinicians need a deeper understanding of how resistance training helps people with FM, so as to prescribe more specific, personalized resistance training to their patients. PMID- 26377809 TI - Reverse-transcription, loop-mediated isothermal amplification assay for the sensitive and rapid detection of H10 subtype avian influenza viruses. AB - BACKGROUND: The H10 subtype avian influenza viruses (H10N4, H10N5 and H10N7) have been reported to cause disease in mammals, and the first human case of H10N8 subtype avian influenza virus was reported in 2013. Recently, H10 subtype avian influenza viruses (AIVs) have been followed more closely, but routine diagnostic tests are tedious, less sensitive and time consuming, rapid molecular detection assays for H10 AIVs are not available. METHODS: Based on conserved sequences within the HA gene of the H10 subtype AIVs, specific primer sets of H10 subtype of AIVs were designed and assay reaction conditions were optimized. A reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay was established for the rapid detection of H10 subtype AIVs. The specificity was validated using multiple subtypes of AIVs and other avian respiratory pathogens, and the limit of detection (LOD) was tested using concentration gradient of in vitro-transcribed RNA. RESULTS: The established assay was performed in a water bath at 63 degrees C for 40 min, and the amplification result was visualized directly as well as under daylight reflections. The H10-RT-LAMP assay can specifically amplify H10 subtype AIVs and has no cross-reactivity with other subtypes AIVs or avian pathogens. The LOD of the H10-RT-LAMP assay was 10 copies per MUL of in vitro-transcribed RNA. CONCLUSIONS: The RT-LAMP method reported here is demonstrated to be a potentially valuable means for the detection of H10 subtype AIV and rapid clinical diagnosis, being fast, simple, and low in cost. Consequently, it will be a very useful screening assay for the surveillance of H10 subtype AIVs in underequipped laboratories as well as in field conditions. PMID- 26377810 TI - Socioeconomic inequalities in breast and cervical screening coverage in England: are we closing the gap? AB - OBJECTIVE: Health policy in the UK is committed to tackling inequalities in cancer screening participation. We examined whether socioeconomic inequalities in breast and cervical cancer screening participation in England have reduced over five years. METHODS: Cross-sectional analyses compared cervical and breast screening coverage between 2007/8 and 2012/13 in Primary Care Trusts (PCTs) in England in relation to area-level income deprivation. RESULTS: At the start and the end of this five year period, there were socioeconomic inequalities in screening coverage for breast and cervical screening. Inequalities were highest for breast screening. Over time, the coverage gap between the highest and lowest quintiles of income deprivation significantly reduced for breast screening (from 12.3 to 8.3 percentage points), but not for cervical screening (5.3 to 4.9 percentage points). CONCLUSIONS: Efforts to reduce screening inequalities appear to have resulted in a significant improvement in equitable delivery of breast screening, although not of cervical screening. More work is needed to understand the differences, and see whether broader lessons can be learned from the reduction of inequalities in breast screening participation. PMID- 26377811 TI - Overexpression of Trps1 contributes to tumor angiogenesis and poor prognosis of human osteosarcoma. AB - BACKGROUND: Trichorhinophalangeal syndrome 1 (Trps1) gene is a member of GATA transcription factor family and has an important function in tumorigenesis and progression. However, there are rare studies on its roles in carcinogenesis and prognostic significance in human osteosarcoma. METHODS: The expression of Trps1 was detected by immunohistochemistry, and MVD was evaluated to determine the amounts of microvessels by counting CD31-positive endothelial cells. RESULTS: Of the 74 cases that underwent study, Trps1-positive cases were 24. And it was associated with MVD significantly (P = 0.008). The data also exhibited more cases of remote metastasis (P = 0.013) and higher Enneking stage (P = 0.017) in Trps1 positive group compared to Trps1-negative group. Univariate analysis revealed that distant metastasis, MVD and Trps1 expression were associated with a lower 3 year overall survival rate and disease-free survival rate (P = 0.003, and P = 0.012 respectively). Furthermore, Trps1 and distant metastasis retained their significant prognostic effects on patients survival rate by multivariate analysis (P < 0.05). CONCLUSIONS: Trps1 plays a crucial role in osteosarcoma angiogenesis, metastasis and clinical surgical stage. Trps1 can be a novel promising prognostic marker and therapeutic target, and antiangiogenic therapy which targets Trps1 molecule in patients with osteosarcoma may lead to improved prognosis and longer term survival. PMID- 26377812 TI - High-level production of membrane proteins in E. coli BL21(DE3) by omitting the inducer IPTG. AB - BACKGROUND: For membrane protein production, the Escherichia coli T7 RNA polymerase (T7 RNAP)-based protein production strain BL21(DE3) in combination with T7-promoter based expression vectors is widely used. Cells are routinely cultured in Lysogeny broth (LB medium) and expression of the chromosomally localized t7rnap gene is governed by the isopropyl-beta-D-1-thiogalactopyranoside (IPTG) inducible lacUV5 promoter. The T7 RNAP drives the expression of the plasmid borne gene encoding the recombinant membrane protein. Production of membrane proteins in the cytoplasmic membrane rather than in inclusion bodies in a misfolded state is usually preferred, but often hampered due to saturation of the capacity of the Sec-translocon, resulting in low yields. RESULTS: Contrary to expectation we observed that omission of IPTG from BL21(DE3) cells cultured in LB medium can lead to significantly higher membrane protein production yields than when IPTG is added. In the complete absence of IPTG cultures stably produce membrane proteins in the cytoplasmic membrane, whereas upon the addition of IPTG membrane proteins aggregate in the cytoplasm and non-producing clones are selected for. Furthermore, in the absence of IPTG, membrane proteins are produced at a lower rate than in the presence of IPTG. These observations indicate that in the absence of IPTG the Sec-translocon capacity is not/hardly saturated, leading to enhanced membrane protein production yields in the cytoplasmic membrane. Importantly, for more than half of the targets tested the yields obtained using un-induced BL21(DE3) cells were higher than the yields obtained in the widely used membrane protein production strains C41(DE3) and C43(DE3). Since most secretory proteins reach the periplasm via the Sec-translocon, we also monitored the production of three secretory recombinant proteins in the periplasm of BL21(DE3) cells in the presence and absence of IPTG. For all three targets tested omitting IPTG led to the highest production levels in the periplasm. CONCLUSIONS: Omission of IPTG from BL21(DE3) cells cultured in LB medium provides a very cost- and time effective alternative for the production of membrane and secretory proteins. Therefore, we recommend that this condition is incorporated in membrane and secretory protein production screens. PMID- 26377813 TI - Safety and Feasibility of Open Chest Epicardial Mapping and Ablation of Ventricular Tachycardia During the Period of Left Ventricular Assist Device Implantation. AB - INTRODUCTION: Patients undergoing catheter ablation for ventricular tachycardia (VT) may require epicardial mapping. In patients with end-stage heart failure, hybrid surgical epicardial mapping and ablation during the period of left ventricular assist device (LVAD) implantation may be considered in select patients to reduce post-LVAD ventricular tachycardia. METHODS AND RESULTS: From March 2009 to October 2012, 5 patients (4 men and 1 woman, age range 52-73 years) underwent open chest electrophysiology study and epicardial mapping for recurrent ventricular tachycardia while the heart was exposed during the period of LVAD implantation. Epicardial mapping was considered if patients had recurrent VT despite failed prior endocardial ablation and/or electrocardiogram (EKG) features of an epicardial exit. Activation and/or a substrate mapping approach were employed during all procedures. Three of 5 patients (60%) had acute procedural success. In all patients, VT was either eliminated or significantly reduced with epicardial ablation. One patient had mediastinal bleeding delaying sternal closure. During a follow-up period of 363 +/- 368 days, 4 patients died due to nonarrhythmic causes. CONCLUSIONS: Open-chest hybrid epicardial mapping and ablation for recurrent VT is feasible and can be considered in select patients during the period of LVAD implantation. PMID- 26377814 TI - Systematic synergy modeling: understanding drug synergy from a systems biology perspective. AB - Owing to drug synergy effects, drug combinations have become a new trend in combating complex diseases like cancer, HIV and cardiovascular diseases. However, conventional synergy quantification methods often depend on experimental dose response data which are quite resource-demanding. In addition, these methods are unable to interpret the explicit synergy mechanism. In this review, we give representative examples of how systems biology modeling offers strategies toward better understanding of drug synergy, including the protein-protein interaction (PPI) network-based methods, pathway dynamic simulations, synergy network motif recognitions, integrative drug feature calculations, and "omic"-supported analyses. Although partially successful in drug synergy exploration and interpretation, more efforts should be put on a holistic understanding of drug disease interactions, considering integrative pharmacology and toxicology factors. With a comprehensive and deep insight into the mechanism of drug synergy, systems biology opens a novel avenue for rational design of effective drug combinations. PMID- 26377815 TI - Heterogeneity correction for intensity-modulated frameless SRS in pituitary and cavernous sinus tumors: a retrospective study. AB - BACKGROUND: Frameless immobilization allows for planning and quality assurance of intensity-modulated radiosurgery (IM-SRS) plans. We tested the hypothesis that IM SRS planning with uniform tissue density corrections results in dose inaccuracy compared to heterogeneity-corrected algorithms. METHODS: Fifteen patients with tumors of the pituitary or cavernous sinus underwent frameless IM-SRS. Treatment planning CT and MRI scans were obtained and fused to delineate the tumor, optic nerves, chiasm, and brainstem. The plan was developed with static gantry IM-SRS fields using a pencil beam (PB), analytical anisotropic (AAA), and Acuros XB (AXB) algorithms. We evaluated measures of target coverage as well as doses to organs at risk (OAR) for each algorithm. We compared the results of each algorithm in the cases where PTV overlapped OAR (n = 10) to cases without overlapping OAR with PTV (n = 5). Utilizing film dosimetry, we measured the dose distribution for each algorithm through a uniform density target to a rando phantom with non-uniform density of air, tissue, and bone. RESULTS: There was no difference in target coverage measured by DMaxPTV, DMinPTV, D95%PTV, or the isodose surface (IDS) covering 95% of the PTV regardless of algorithm. However, there were differences in dose to OAR. PB predicted higher (p < 0.05) Dmax for the brainstem, chiasm, right optic nerve, and left optic nerve. In cases of PTV overlapping an optic nerve (n = 7), PB was unable to limit dose to 8 Gy while achieving PTV coverage (PB 855 cGy vs. AAA 769 cGy, p = 0.05 vs. AXB 658 cGy, p = 0.03). Within the rando phantom, the PB and AAA algorithms over-estimated the dose delivered in the bone-tissue-air interface of the sinus (+17%), while the AXB algorithm closely predicted the actual dose delivered through the inhomogeneous tissue (+/- 1 % max, p < 0.05). CONCLUSIONS: Patients undergoing frameless SRS benefit from heterogeneity corrected dose plans when the lesion lies in areas of widely varying tissue density and near critical normal structures such as the skull base. Film dosimetry confirms that the AXB dose calculation algorithm more accurately predicts actual dose delivered though tissues of varying densities than PB or AAA dose calculation algorithms. PMID- 26377816 TI - Well-Being and Safety Among Inpatient Psychiatric Staff: The Impact of Conflict, Assault, and Stress Reactivity. AB - Psychiatric staff are faced with multiple forms of hostility, aggression, and assault at work, collectively referred to as workplace violence, which typically is activated by patients but can also come from coworkers and supervisors. Whether workplace violence adversely affects staff well-being may be related not only to its presence, but also to an individual's stress reactivity. At a large public psychiatric hospital, an online survey was completed by 323 clinical care staff, of whom 69.5 % had experienced physical assault in the previous 12 months. Staff well-being (depression, anger, and physical health) and staff safety concerns were adversely affected by conflicts with other staff members and by individual reactivity to social conflict and to assault. To improve staff well being, in addition to safety protocols, interventions should target staff relationships, personal health maintenance practices, and individual coping skills for dealing with adverse workplace experiences. PMID- 26377817 TI - An R2R3-MYB transcription factor regulates carotenoid pigmentation in Mimulus lewisii flowers. AB - Carotenoids are yellow, orange, and red pigments that contribute to the beautiful colors and nutritive value of many flowers and fruits. The structural genes in the highly conserved carotenoid biosynthetic pathway have been well characterized in multiple plant systems, but little is known about the transcription factors that control the expression of these structural genes. By analyzing a chemically induced mutant of Mimulus lewisii through bulk segregant analysis and transgenic experiments, we have identified an R2R3-MYB, Reduced Carotenoid Pigmentation 1 (RCP1), as the first transcription factor that positively regulates carotenoid biosynthesis during flower development. Loss-of-function mutations in RCP1 lead to down-regulation of all carotenoid biosynthetic genes and reduced carotenoid content in M. lewisii flowers, a phenotype recapitulated by RNA interference in the wild-type background. Overexpression of this gene in the rcp1 mutant background restores carotenoid production and, unexpectedly, results in simultaneous decrease of anthocyanin production in some transgenic lines by down regulating the expression of an activator of anthocyanin biosynthesis. Identification of transcriptional regulators of carotenoid biosynthesis provides the 'toolbox' genes for understanding the molecular basis of flower color diversification in nature and for potential enhancement of carotenoid production in crop plants via genetic engineering. PMID- 26377819 TI - Description of the Baudet Surgical Technique and Introduction of a Systematic Method for Training Surgeons to Perform Male-to-Female Sex Reassignment Surgery. AB - INTRODUCTION: Male-to-female sex reassignment surgery involves three main procedures, namely, clitoroplasty, new urethral meatoplasty and vaginopoiesis. Herein we describe the key steps of our surgical technique. METHODS: Male-to female sex reassignment surgery includes the following 14 key steps which are documented in this article: (1) patient installation and draping, (2) urethral catheter placement, (3) scrotal incision and vaginal cavity formation, (4) bilateral orchidectomy, (5) penile skin inversion, (6) dismembering of the urethra from the corpora, (7) neoclitoris formation, (8) neoclitoris refinement, (9) neovaginalphallic cylinder formation, (10) fixation of the neoclitoris, (11) neovaginalphallic cylinder insertion, (12) contouring of the labia majora and positioning the neoclitoris and urethra, (13) tie-over dressing and (14) compression dressing. RESULTS: The size and position of the neoclitoris, position of the urethra, adequacy of the neovaginal cavity, position and tension on the triangular flap, size of the neo labia minora, size of the labia majora, symmetry and ease of intromission are important factors when considering the immediate results of the surgery. We present our learning process of graduated responsibility for optimisation of these results. We describe our postoperative care and the possible complications. CONCLUSION: Herein, we have described the 14 steps of the Baudet technique for male-to-female sex reassignment surgery which include clitoroplasty, new urethral meatoplasty and vaginopoiesis. The review of each key stage of the procedure represents the first step of our global teaching process. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. PMID- 26377818 TI - A General Synthetic Approach for Designing Epitope Targeted Macrocyclic Peptide Ligands. AB - We describe a general synthetic strategy for developing high-affinity peptide binders against specific epitopes of challenging protein biomarkers. The epitope of interest is synthesized as a polypeptide, with a detection biotin tag and a strategically placed azide (or alkyne) presenting amino acid. This synthetic epitope (SynEp) is incubated with a library of complementary alkyne or azide presenting peptides. Library elements that bind the SynEp in the correct orientation undergo the Huisgen cycloaddition, and are covalently linked to the SynEp. Hit peptides are tested against the full-length protein to identify the best binder. We describe development of epitope-targeted linear or macrocycle peptide ligands against 12 different diagnostic or therapeutic analytes. The general epitope targeting capability for these low molecular weight synthetic ligands enables a range of therapeutic and diagnostic applications, similar to those of monoclonal antibodies. PMID- 26377820 TI - Shouldn't Propranolol Be Used to Treat All Haemangiomas? AB - INTRODUCTION: Infantile haemangioma is the most common childhood tumour. These tumours can cause significant functional and cosmetic problems. While there are many treatment modalities, propranolol is increasingly being recognised as the first-line treatment of problematic haemangiomas. This study investigates the use of oral propranolol for the treatment of all haemangiomas at a tertiary children's hospital. METHOD: This is a retrospective study evaluating 15 children (3 boys and 12 girls) presenting at a tertiary children's hospital with infantile haemangioma during a 24-month period. The protocol consisted of pre-treatment ultrasonic evaluation of the lesion, followed by the commencement of propranolol therapy (2 mg/kg orally in two divided doses), with repeat imaging performed at 16-24 weeks in order to document the dimensional changes. Adverse effects of propranolol were documented. Intralesional bleomycin was utilised as a second line modality of treatment for large or problematic haemangiomas with inadequate regression in size after oral propranolol therapy. RESULT: Fifteen (15) patients with a mean age of 7 months (Range: 3-14 months) presented with haemangiomas. Ten patients presented with lesions affecting the head and neck region (67%). Three patients presented with an ulcerated haemangioma, which responded to propranolol and simple dressings and all healed completely. The average decrease in size between the ultrasonography procedures was 48.87%. Only one patient showed no improvement. No side effects were reported. Concomitant bleomycin treatment was reserved for large problematic haemangiomas and proved successful at speeding up the involution process. CONCLUSION: This study suggests that propranolol become the first-line treatment of choice for all haemangiomas. It has proven to be effective and safe for reducing the size of all haemangiomas during the proliferative phase. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. PMID- 26377821 TI - A Meta-analysis of Postoperative Complications of Tissue Expander/Implant Breast Reconstruction Using Acellular Dermal Matrix. AB - BACKGROUND: Acellular dermal matrix (ADM) is commonly used for tissue expander/implant breast (TE/I-based) reconstruction. But the relation between ADM and postoperative complications remains controversial. A few meta-analyses were conducted in 2011-2012 and the result revealed that ADM can increase the risk of complications. The purpose of our study is to offer updated evidence for ADM clinical application by analyzing the effect of ADM on complications of TE/I based breast reconstruction. METHODS: The literature published from January 2010 to February 2015 was searched in EMbase, Medline, Science Direct, the Cochrane Central Register of Controlled Trials (CENTRAL), CBMdisc, CNKI, VIP, and the references of those included studies were also searched by hand. According to inclusive criteria, 11 studies were selected and the values were extracted from the included literature. Complications with four different categories assigned for overall complications, infection, hematoma/seroma, and explantation were collected. RevMan 5.1 was used for meta-analysis. The evidence level was assessed by using the GRADE system. RESULTS: Eleven published studies were included. The results showed that compared to the control group, the ADM group increased the rate of overall complications (OR = 1.33, 95% CI 1.03-1.70, p = 0.03), infection (OR = 1.47, 95% CI 1.04-2.06, p = 0.03), hematoma/seroma (OR = 1.66, 95% CI 1.13 2.44, p = 0.01), but there was no significant difference in explantation (OR = 1.37, 95% CI 0.89-2.11, p = 0.15). Based on the GRADE system, all the evidence was at level C and weak recommendation. CONCLUSIONS: In TE/I-based breast reconstruction, ADM increased the incidence of overall complications, infection, and hematoma/seroma; the incidence of explantation remains unknown. For the poor quality of the original studies, a prudent choice is suggested; and more high quality, large-sample studies are needed. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://www.springer.com/00266. PMID- 26377822 TI - Important Description of a Minimally Invasive Procedure for Axillary Osmidrosis. PMID- 26377823 TI - A Simple Method of Cartilage Ekartation During a Nasal Dorsal Reduction. PMID- 26377825 TI - Bio-efficacy of new long-lasting insecticide-treated bed nets against Anopheles funestus and Anopheles gambiae from central and northern Mozambique. AB - BACKGROUND: Long-lasting insecticide-treated nets (LLINs) are one of the main methods used for controlling malaria transmission in Mozambique. The proliferation of several types of LLINs and the re-emergence of insecticide resistance in the local vector populations poses challenges to the local malaria control programme on selecting suitable insecticide-based vector control products. Therefore, this study evaluated the insecticide susceptibility and bio efficacy of selected new LLINs against wild populations of Anopheles funestus sensu lato and A. gambiae s.l. from Northern and Central Mozambique. The study also investigated whether the insecticide contents on the LINNs fabrics were within the WHOPES recommended target range. METHODS: The susceptibility of 2-5 day old wild female A. funestus and A. gambiae sensu stricto against the major classes of insecticides used for vector control, viz: deltamethrin (0.05 %), permethrin (0.75 %), propoxur (0.1 %), bendiocarb (0.1 %) and DDT (4 %), was determined using WHO cylinder susceptibility tests. WHO cone bioassays were conducted to determine the bio-efficacy of both pyrethroid-only LLINs (Olyset((r)), Permanet 2.0((r)), NetProtect((r)) and Interceptor((r))) and, Permanet 3.0((r)) a combination LLIN against A. funestus s.s, from Balama, Mocuba and Milange districts, respectively. The bio-efficacy of LLINs against the insectary-susceptible A. arabiensis (Durban strain) was assessed, as well. Untreated bed net swatches were used as negative controls. Chemical analyses, by high performance liquid chromatography, were undertaken to assess whether the insecticide contents on the LLINs fabrics fell within recommended target dose ranges. The frequency of kdr gene mutations was determined from a random sample of A. gambiae s.s. from both WHO susceptibility and cone bioassay experiments. RESULTS: Anopheles funestus from Balama district showed resistance to deltamethrin and possible resistance to permethrin, propoxur and bendiocarb, whilst A. gambiae from Mocuba district was susceptible to deltamethrin, bendiocarb and propoxur. There were no kdr mutants found in the sample of 256 A. gambiae tested. Overall, 186 LLIN swatches were tested. Mosquitoes exposed to Olyset((r)) had the lowest knockdown (+/-standard error) and mortality rate (+/ standard error) in all studied sites regardless of vectors species tested. Permanet 3.0 showed the highest bio-efficacy independent of vector species tested and level of insecticide resistance detected. All types of LLINs effectively killed susceptible A. arabiensis Durban strain. The insecticide content of Olyset((r)) and Permanet 2.0((r)) was higher than the target dose but NetProtect((r)) had a lower insecticide content than the target dose. CONCLUSION: The study shows evidence of considerable heterogeneity in both insecticide susceptibility and the level of bio-efficacy of commonly available types of LLINs against wild A. funestus and A. gambiae from Balama, Mocuba and Milange districts, located in north and centre of Mozambique. The findings suggest that vector control approaches combining different types of insecticides might help to tackle the apparent problem of pyrethroid resistance in the vector populations from these three sites. Results from bioassays on laboratory-susceptible A. arabiensis strongly suggest that LLINs can offer some protection against susceptible malaria vectors. PMID- 26377824 TI - Preference of methadone maintenance patients for the integrative and decentralized service delivery models in Vietnam. AB - BACKGROUND: Integrating and decentralizing services are essential to increase the accessibility and provide comprehensive care for methadone patients. Moreover, they assure the sustainability of a HIV/AIDS prevention program by reducing the implementation cost. This study aimed to measure the preference of patients enrolling in a MMT program for integrated and decentralized MMT clinics and then further examine related factors. METHODS: A cross-sectional study was conducted among 510 patients receiving methadone at 3 clinics in Hanoi. Structured questionnaires were used to collect data about the preference for integrated and decentralized MMT services. Covariates including socio-economic status; health related quality of life (using EQ-5D-5 L instrument) and HIV status; history of drug use along with MMT treatment; and exposure to the discrimination within family and community were also investigated. Multivariate logistic regression with polynomial fractions was used to identify the determinants of preference for integrative and decentralized models. RESULTS: Of 510 patients enrolled, 66.7 and 60.8 % preferred integrated and decentralized models, respectively. The main reason for preferring the integrative model was the convenience of use of various services (53.2 %), while more privacy (43.5 %) was the primary reason to select stand-alone model. People preferred the decentralized model primarily because of travel cost reduction (95.0 %), while the main reason for not selecting the model was increased privacy (7.7 %). After adjusting for covariates, factors influencing the preference for integrative model were poor socioeconomic status, anxiety/depression, history of drug rehabilitation, and ever disclosed health status; while exposure to community discrimination inversely associated with this preference. In addition, people who were self-employed, had a longer duration of MMT, and use current MMT with comprehensive HIV services were less likely to select decentralized model. CONCLUSION: In conclusion, the study confirmed the high preference of MMT patients for the integrative and decentralized MMT service delivery models. The convenience of healthcare services utilization and reduction of geographical barriers were the main reasons to use those models within drug use populations in Vietnam. Countering community stigma and encouraging communication between patients and their societies needed to be considered when implementing those models. PMID- 26377826 TI - Channel Interaction and Current Level Affect Across-Electrode Integration of Interaural Time Differences in Bilateral Cochlear-Implant Listeners. AB - Sensitivity to interaural time differences (ITDs) is important for sound localization. Normal-hearing listeners benefit from across-frequency processing, as seen with improved ITD thresholds when consistent ITD cues are presented over a range of frequency channels compared with when ITD information is only presented in a single frequency channel. This study aimed to clarify whether cochlear-implant (CI) listeners can make use of similar processing when being stimulated with multiple interaural electrode pairs transmitting consistent ITD information. ITD thresholds for unmodulated, 100-pulse-per-second pulse trains were measured in seven bilateral CI listeners using research interfaces. Consistent ITDs were presented at either one or two electrode pairs at different current levels, allowing for comparisons at either constant level per component electrode or equal overall loudness. Different tonotopic distances between the pairs were tested in order to clarify the potential influence of channel interaction. Comparison of ITD thresholds between double pairs and the respective single pairs revealed systematic effects of tonotopic separation and current level. At constant levels, performance with double-pair stimulation improved compared with single-pair stimulation but only for large tonotopic separation. Comparisons at equal overall loudness revealed no benefit from presenting ITD information at two electrode pairs for any tonotopic spacing. Irrespective of electrode-pair configuration, ITD sensitivity improved with increasing current level. Hence, the improved ITD sensitivity for double pairs found for a large tonotopic separation and constant current levels seems to be due to increased loudness. The overall data suggest that CI listeners can benefit from combining consistent ITD information across multiple electrodes, provided sufficient stimulus levels and that stimulating electrode pairs are widely spaced. PMID- 26377827 TI - Shear banding in entangled polymers in the micron scale gap: a confocal rheoscopic study. AB - Recent shear experiments in well-entangled polymer solutions demonstrated that interfacial wall slip is the only source of shear rate loss and there is no evidence of shear banding in the micron scale gap. In this work, we experimentally elucidate how molecular parameters such as slip length, b, influence shear inhomogeneity of entangled polybutadiene (PBD) solutions during shear in a small gap H ~ 50 MUm. Simultaneous rheometric and velocimetric measurements are performed on two PBD solutions with the same level of entanglements (Z = 54) in two PBD solvents with molecular weights of 1.5 kg mol( 1) and 10 kg mol(-1) that possess different levels of shear inhomogeneity (2bmax/H = 17 and 240). For the PBD solution made with a low molecular weight PBD solvent of 1.5 kg mol(-1), wall slip is the dominant response within the accessible range of the shear rate, i.e., up to the nominal Weissenberg number (Wi) as high as 290. On the other hand, wall slip is minimized using a high molecular-weight PBD solvent of 10 kg mol(-1) so that bulk shear banding is observed to take place in the steady state for Wi > 100. Finally, these findings and previous results are in good agreement with our recently proposed phase diagram in the parameter space of apparent Wi versus 2bmax/H suggesting that shear banding develops across the micron scale gap when the imposed Wi exceeds 2bmax/H [Wang et al., Macromolecules, 2011, 44, 183]. PMID- 26377828 TI - High-Throughput Tag-Sequencing Analysis of Early Events Induced by Ochratoxin A in HepG-2 Cells. AB - Ochratoxin A (OTA) is produced by fungi of the species Aspergillus and Penicillium. OTA has displayed hepatotoxicity in mammals. Although recent studies have indicated that OTA influences liver function, little is known regarding its impact on differential early liver toxicity. In this study, we report high throughput tag-sequencing (Tag-seq) analysis of the transcriptome using Solexa Analyzer platform after 4 h of OTA treatment on HepG-2 cells. The analyses of differentially expressed genes revealed the substantial changes. A total of 21,449 genes were identified and quantified, with 2726 displaying significantly altered expression levels. Expression level data were then integrated with a network of gene-gene interactions, and biological pathways to obtain a systems level view of changes in the transcriptome that occur with OTA resistance. Our data suggest that OTA exposure leads to an imbalance in zinc finger expression and shed light on splicing factor and mitochondrial-based mechanisms. PMID- 26377829 TI - Relations of Neighborhood Environment Influences, Physical Activity, and Active Transportation to/from School across African American, Latino American, and White Girls in the United States. AB - BACKGROUND: Neighborhood environment influences may be particularly important for understanding physical activity (PA) patterns across ethnic subgroups of early adolescent girls. PURPOSE: This study examined relationships between neighborhood variables, moderate to vigorous physical activity (MVPA), and active transportation to/from school across African American, Latino American, and White early adolescent girls living in an urban/suburban community in the northwestern U.S.A. Relations between the neighborhood variables across ethnic groups also were examined. METHOD: The sample comprised 372 African American, Latino American, and White girls living in the U.S.A. (mean age = 12.06 years; SD = 1.69). RESULTS: Data were analyzed using multiple-sample structural equation modeling. Results showed that girls' MVPA was positively related to physical activity facility accessibility and negatively related to age. Active transport was positively related to physical activity facility accessibility, neighborhood walkability, and age, and negatively related to distance to the nearest school and household income. CONCLUSIONS: Findings highlight the importance of both perceived and objective neighborhood influences on girls' MVPA and active transport. Consistencies in findings across African American, Latino American, and White girls suggest that neighborhood-level PA promotion has the potential for broad impact across all three ethnic groups. PMID- 26377830 TI - Burr-hole Irrigation with Closed-system Drainage for the Treatment of Chronic Subdural Hematoma: A Meta-analysis. AB - There is controversy among neurosurgeons regarding whether irrigation or drainage is necessary for achieving a lower revision rate for the treatment of chronic subdural hematoma (CSDH) using burr-hole craniostomy (BHC). Therefore, we performed a meta-analysis of all available published reports. Multiple electronic health databases were searched to identify all studies published between 1989 and June 2012 that compared irrigation and drainage. Data were processed by using Review Manager 5.1.6. Effect sizes are expressed as pooled odds ratio (OR) estimates. Due to heterogeneity between studies, we used the random effect of the inverse variance weighted method to perform the meta-analysis. Thirteen published reports were selected for this meta-analysis. The comprehensive results indicated that there were no statistically significant differences in mortality or complication rates between drainage and no drainage (P > 0.05). Additionally, there were no differences in recurrence between irrigation and no irrigation (P > 0.05). However, the difference between drainage and no drainage in recurrence rate reached statistical significance (P < 0.01). The results from this meta analysis suggest that burr-hole surgery with closed-system drainage can reduce the recurrence of CSDH; however, irrigation is not necessary for every patient. PMID- 26377831 TI - Temperature seasonality during fry out-migration influences the survival of hatchery-reared chum salmon Oncorhynchus keta. AB - Among years, fry-to-adult survival of hatchery-reared chum salmon Oncorhynchus keta was positively correlated with the length (in days) of the fry out-migration period with temperatures suitable for migration. Furthermore, survival decreased with increasing difference in mean temperature between May and June. Thus, prolonged out-migration periods increased the probability of survival from fry to adult, lending support to the hypothesis that long migration periods decrease the risk of mortality (bet-hedging), and increase the probability of migration when environmental conditions in fresh water and the ocean are suitable (match mismatch). PMID- 26377832 TI - Response to comment on: "antibiotic use varies substantially among adults--a cross-national study from five European Countries in the ARITMO project". PMID- 26377833 TI - Application of the Nordtest method for "real-time" uncertainty estimation of on line field measurement. AB - Field sensor measurements are becoming more common for environmental monitoring. Solutions for enhancing reliability, i.e. knowledge of the measurement uncertainty of field measurements, are urgently needed. Real-time estimations of measurement uncertainty for field measurement have not previously been published, and in this paper, a novel approach to the automated turbidity measuring system with an application for "real-time" uncertainty estimation is outlined based on the Nordtest handbook's measurement uncertainty estimation principles. The term real-time is written in quotation marks, since the calculation of the uncertainty is carried out using a set of past measurement results. There are two main requirements for the estimation of real-time measurement uncertainty of online field measurement described in this paper: (1) setting up an automated measuring system that can be (preferably remotely) controlled which measures the samples (water to be investigated as well as synthetic control samples) the way the user has programmed it and stores the results in a database, (2) setting up automated data processing (software) where the measurement uncertainty is calculated from the data produced by the automated measuring system. When control samples with a known value or concentration are measured regularly, any instrumental drift can be detected. An additional benefit is that small drift can be taken into account (in real-time) as a bias value in the measurement uncertainty calculation, and if the drift is high, the measurement results of the control samples can be used for real-time recalibration of the measuring device. The procedure described in this paper is not restricted to turbidity measurements, but it will enable measurement uncertainty estimation for any kind of automated measuring system that performs sequential measurements of routine samples and control samples/reference materials in a similar way as described in this paper. PMID- 26377834 TI - Effects of surface stability on the morphological transformation of metals and metal oxides as investigated by first-principles calculations. AB - Morphology is a key property of materials. Owing to their precise structure and morphology, crystals and nanocrystals provide excellent model systems for joint experimental and theoretical investigations into surface-related properties. Faceted polyhedral crystals and nanocrystals expose well-defined crystallographic planes depending on the synthesis method, which allow for thoughtful investigations into structure-reactivity relationships under practical conditions. This feature article introduces recent work, based on the combined use of experimental findings and first-principles calculations, to provide deeper knowledge of the electronic, structural, and energetic properties controlling the morphology and the transformation mechanisms of different metals and metal oxides: Ag, anatase TiO2, BaZrO3, and alpha-Ag2WO4. According to the Wulff theorem, the equilibrium shapes of these systems are obtained from the values of their respective surface energies. These investigations are useful to gain further understanding of how to achieve morphological control of complex three dimensional crystals by tuning the ratio of the surface energy values of the different facets. This strategy allows the prediction of possible morphologies for a crystal and/or nanocrystal by controlling the relative values of surface energies. PMID- 26377835 TI - Comparative Efficacies of Long-Term Serial Transplantation of Syngeneic, Allogeneic, Xenogeneic, or CTLA4Ig-Overproducing Xenogeneic Adipose Tissue Derived Mesenchymal Stem Cells on Murine Systemic Lupus Erythematosus. AB - Allogeneic and xenogeneic transplantation are suitable alternatives for treating patients with stem cell defects and autoimmune diseases. The purpose of this study was to compare the effects of long-term serial transplantation of adipose tissue-derived mesenchymal stem cells (ASCs) from (NZB * NZW) F1 mice (syngeneic), BALB/c mice (allogeneic), or humans (xenogeneic) on systemic lupus erythematosus (SLE). The effects of transplanting human ASCs overproducing CTLA4Ig (CTLA4Ig-hASC) were also compared. Animals were divided into five experimental groups, according to the transplanted cell type. Approximately 500,000 ASCs were administered intravenously every 2 weeks from 6 to 60 weeks of age to all mice except for the control mice, which received saline. The human ASC groups (hASC and CTLA4Ig-hASC) showed a 13-week increase in average life spans and increased survival rates and decreased blood urea nitrogen, proteinuria, and glomerular IgG deposition. The allogeneic group also showed higher survival rates compared to those of the control, up to 40, 41, 42, 43, 44, 45, 52, and 53 weeks of age. Syngeneic ASC transplantation did not accelerate the mortality of the mice. The mean life span of both the syngeneic and allogeneic groups was prolonged for 6-7 weeks. Both human ASC groups displayed increased serum interleukin-10 and interleukin-4 levels, whereas both mouse ASC groups displayed significantly increased GM-CSF and interferon-gamma levels in the serum. The strongest humoral immune response was induced by xenogeneic transplantation, followed by allogeneic, CTLA4Ig-xenogeneic, and syngeneic transplantations. Long term serial transplantation of the ASCs from various sources displayed different patterns of cytokine expression and humoral responses, but all of them increased life spans in an SLE mouse model. PMID- 26377838 TI - Long-term costs of introducing HPV-DNA post-treatment surveillance to national cervical cancer screening in Ireland. AB - INTRODUCTION: Co-testing (cytology plus human papillomavirus DNA testing) as part of cervical cancer surveillance in Ireland increases one-time testing costs. Of interest to policy makers was the long-term impact of these costs accompanied by decreases in intensity of recalls for women with no detected abnormalities. METHODS: A cost analysis of cytology-only and co-testing strategy was implemented using decision analytic modeling, aggregating testing utilization and costs for each of the two strategies over 12 years. RESULTS: Aggregated incremental costs of the co-testing strategy were positive for the first 3 years but became negative thereafter, generating a cost savings of roughly ?20 million in favor of the cytology-only strategy over a 12-year period. Results were robust over a range of sensitivity analyses with respect to discount and attrition rates. DISCUSSION: This analysis provided valuable information to policy makers contributing to the introduction of co-testing for post-treatment surveillance (PTS) in Ireland. PMID- 26377837 TI - Exome sequencing of lymphomas from three dog breeds reveals somatic mutation patterns reflecting genetic background. AB - Lymphoma is the most common hematological malignancy in developed countries. Outcome is strongly determined by molecular subtype, reflecting a need for new and improved treatment options. Dogs spontaneously develop lymphoma, and the predisposition of certain breeds indicates genetic risk factors. Using the dog breed structure, we selected three lymphoma predisposed breeds developing primarily T-cell (boxer), primarily B-cell (cocker spaniel), and with equal distribution of B- and T-cell lymphoma (golden retriever), respectively. We investigated the somatic mutations in B- and T-cell lymphomas from these breeds by exome sequencing of tumor and normal pairs. Strong similarities were evident between B-cell lymphomas from golden retrievers and cocker spaniels, with recurrent mutations in TRAF3-MAP3K14 (28% of all cases), FBXW7 (25%), and POT1 (17%). The FBXW7 mutations recurrently occur in a specific codon; the corresponding codon is recurrently mutated in human cancer. In contrast, T-cell lymphomas from the predisposed breeds, boxers and golden retrievers, show little overlap in their mutation pattern, sharing only one of their 15 most recurrently mutated genes. Boxers, which develop aggressive T-cell lymphomas, are typically mutated in the PTEN-mTOR pathway. T-cell lymphomas in golden retrievers are often less aggressive, and their tumors typically showed mutations in genes involved in cellular metabolism. We identify genes with known involvement in human lymphoma and leukemia, genes implicated in other human cancers, as well as novel genes that could allow new therapeutic options. PMID- 26377836 TI - The genome of the vervet (Chlorocebus aethiops sabaeus). AB - We describe a genome reference of the African green monkey or vervet (Chlorocebus aethiops). This member of the Old World monkey (OWM) superfamily is uniquely valuable for genetic investigations of simian immunodeficiency virus (SIV), for which it is the most abundant natural host species, and of a wide range of health related phenotypes assessed in Caribbean vervets (C. a. sabaeus), whose numbers have expanded dramatically since Europeans introduced small numbers of their ancestors from West Africa during the colonial era. We use the reference to characterize the genomic relationship between vervets and other primates, the intra-generic phylogeny of vervet subspecies, and genome-wide structural variations of a pedigreed C. a. sabaeus population. Through comparative analyses with human and rhesus macaque, we characterize at high resolution the unique chromosomal fission events that differentiate the vervets and their close relatives from most other catarrhine primates, in whom karyotype is highly conserved. We also provide a summary of transposable elements and contrast these with the rhesus macaque and human. Analysis of sequenced genomes representing each of the main vervet subspecies supports previously hypothesized relationships between these populations, which range across most of sub-Saharan Africa, while uncovering high levels of genetic diversity within each. Sequence-based analyses of major histocompatibility complex (MHC) polymorphisms reveal extremely low diversity in Caribbean C. a. sabaeus vervets, compared to vervets from putatively ancestral West African regions. In the C. a. sabaeus research population, we discover the first structural variations that are, in some cases, predicted to have a deleterious effect; future studies will determine the phenotypic impact of these variations. PMID- 26377840 TI - Early Changes of Mannose-Binding Lectin, H-Ficolin, and Procalcitonin in Patients with Febrile Neutropenia: A Prospective Observational Study. AB - OBJECTIVE: The significance of mannose-binding lectin (MBL) and H-ficolin deficiency in febrile neutropenic (FN) patients and the correlation of these markers along with consecutive C-reactive protein (CRP) and procalcitonin (PCT) levels during the infectious process are investigated. MATERIALS AND METHODS: Patients with any hematological malignancies who were defined to have "microbiologically confirmed infection", "clinically documented infection", or "fever of unknown origin" were included in this single-center prospective observational study. Serum levels of CRP, PCT, MBL, and H-ficolin were determined on 3 separate occasions: at baseline (between hospital admission and chemotherapy), at the onset of fever, and at the 72nd hour of fever. RESULTS: Forty-six patients (54% male, mean age 41.7 years) with 61 separate episodes of FN were evaluated. Eleven patients (23.9%) had "microbiologically confirmed infection", 17 (37%) had "clinically documented infection", and 18 (39.1%) had "fever of unknown origin". Fourteen (30.4%) patients had low (<500 ng/mL) initial MBL levels and 7 (15.21%) had low (<12,000 ng/mL) H-ficolin levels. Baseline MBL and H-ficolin levels did not significantly change on the first and third days of fever (p=0.076). Gram-negative bacteremia more frequently occurred in those with low initial MBL levels (p=0.006). PCT levels were significantly higher in those with microbiologically documented infections. Mean and median PCT levels were significantly higher in cases with bacteremia. There was no significant difference between hemoculture-positive and-negative patients in terms of CRP levels. CONCLUSION: Monitoring serum H-ficolin levels was shown to be of no benefit in terms of predicting severe infection. Low baseline MBL levels were correlated with high risk of gram-negative bacteremia; however, no significant correlation was shown in the follow-up. Close monitoring of PCT levels is warranted to provide more accurate and specific data while monitoring cases of bacteremia. PMID- 26377841 TI - Influence of Structural Parameters on the Self-Association Properties of Anti-HIV Catanionic Dendrimers. AB - The self-association properties of anti-HIV catanionic dendrimers as multivalent galactosylceramide (GalCer)-derived inhibitors are presented. The study was designed to elucidate the origin of the relatively high cytotoxicity values of these anti-HIV catanionic dendrimers, which have previously been found to exhibit in vitro anti-HIV activity in the submicromolar range. The physicochemical properties of these catanionic dendrimers were studied to tentatively correlate the structural parameters with self-association and biological properties. We can conclude from this study that the absence of correlation between the hydrophobicity and the cytotoxicity of the catanionic systems could be explained by the partial segregation of the different partners of the catanionic entities. PMID- 26377839 TI - Phenotypical diversity of patients with LEOPARD syndrome carrying the worldwide recurrent p.Tyr279Cys PTPN11 mutation. AB - LEOPARD syndrome (LS, OMIM 151100) is a rare monogenic disorder. The name is an acronym of its major features such as multiple lentigines, electrocardiographic conduction defects, ocular hypertelorism, pulmonary stenosis, abnormalities of genitalia, retardation of growth and sensorineural deafness. LS develops due to mutations in the protein-tyrosine phosphatase nonreceptor-type 11, PTPN11. Here, we have investigated a 51-year-old Hungarian male patient affected by LS. Direct sequencing of the PTPN11 gene revealed a worldwide recurrent missense mutation (c.836A/G; p.Tyr279Cys), which has been previously identified in 47 LS patients. Comparison of the clinical phenotypes of our patient and the ones reported in the literature demonstrates great phenotypic diversity despite the same genotype. PMID- 26377843 TI - Survey on parasitic infections in wildcat (Felis silvestris silvestris Schreber, 1777) by scat collection. AB - Wildcats are endangered felid species living in Europe, Asia, and Africa. Regrettably, scientific information on parasites of wildcats is particularly meager and they often rely on data gained by necropsies of a small number of animals. In the present study, scat collection was used to assess the parasite spectrum of European wildcats living in the Etna Park (Sicily, Italy). Scat collection was performed from May to September 2010 by weekly walking four transects for a total of 391 km. Samples were then analyzed by flotation and sedimentation techniques to investigate wildcat parasitic fauna. A total of 121 scats of wildcats were collected, and parasitic forms (i.e., oocysts, eggs, and larvae) were retrieved in 110 (90.9 %) of the samples. Parasites found were Physaloptera sp. (52.1 %), tapeworms (45.5 %), Toxocara cati (43.8 %), Eucoleus aerophilus (27.3 %), Ancylostoma sp. (22.3 %), Troglostrongylus brevior (15.7 %), trematodes (9.9 %), Isospora felis (4.1 %), Cylicospirura sp. (1.7 %), and Acanthocephala (0.8 %). The prevalence of endoparasitic infections herein recorded is similar to that described in other studies conducted using necropsy technique. The species richness of parasites found in the present survey, with a total of nine helminths and one protozoon, is the highest ever reported for wildcat in Europe. Scat collection and examination are reliable and rapid non invasive tools which can be used in a systematic survey design to study the parasite spectrum of wildcat as well as that of other endangered wild species. PMID- 26377844 TI - Significance of serum Il-9 levels in inflammatory bowel disease. AB - IL-9, which may be an inflammatory or regulatory cytokine, can be experimentally produced in a Th17 or modified Th2 context in the presence of T cell receptor (TCR) stimulation. The primary aim of this study was to measure serum IL-9 levels in patients with inflammatory bowel disease (IBD), and evaluate their relationships with the patients' clinical characteristics. The secondary aim was to determine the levels of interferon-gamma (IFN (interferon)-gamma), Th2 cytokines (IL-4, IL-5 and IL-13), and IL-6 in order to clarify the context of detectable peripheral cytokines in which IL-9 is produced.Venous blood samples of 43 IBD patients (20 with Crohn's disease [CD] and 23 with ulcerative colitis [UC]) were analysed by means of quantitative enzyme-linked immunosorbent assays using purified anti-human IL-4, IL-5, IL-13, IFN-gamma, IL-9 and IL-6 antibodies, and the laboratory findings were statistically correlated with their clinical expression.None of the patients showed the peripheral presence of IL-4, IL-5 and IL-13. Forty (93%) were positive for IFN-gamma, thus confirming the presence of Th1 in both UC and CD, and IFN-gamma levels correlated with disease activity (P = 0.045). Eighteen patients (41%) were positive for IL-9, which was associated with a severe prognosis (P <0.001), and 72.2% of the IL-9-positive patients were also IL-6 positive. There was a significant correlation between disease severity and IL-9 in the CD patients (P <0.001), but not in the UC patients (P = 0.1).Our findings confirm the presence of common Th1 cytokines in UC and CD. However the IL-9 positivity indicates the presence of an alternative population of T cells that respond to antigen stimulation and condition the prognosis of IBD. The fact that the same serum IL-9 levels were differentially associated with clinical measures of CD and UC activity suggest that the same cytokine can be produced in different contexts. PMID- 26377842 TI - Course of induced infection by Eimeria krijgsmannni in immunocompetent and immunodeficient mice. AB - Recently, we have demonstrated the utility of Eimeria krijgsmanni as a novel mouse eimerian parasite for elucidating the biological diversity. The parasite showed notable infectivity to mice with various levels of immune status and susceptibility to antimicrobial agents including coccidiostat. However, the detailed lifecycle of E. krijgsmanni had not yet been determined and this information was lacking in discussion of previous findings. In the present study, we clarified the morphological characteristics of E. krijgsmanni and its lifecycle in normal mice, and examined the effects in immunodeficient mice and lifecycle stage for challenge infections after the primary inoculation. In immunocompetent mice, the lifecycle consisted of four asexual stages and the sexual sages followed by formation of oocysts during the prepatent periods. Interestingly, the second-generation meronts were detected in all observation periods after the disappearance of the other stages. For the challenge infection of immunodeficient mice, all developmental stages except for the second generation meronts were temporarily vanished. This finding suggests a "rest" or marked delay in development and a "restart" of the promotion toward the next generations. The second generation meronts may play an important role in the lifecycle of E. krijgsmanni. PMID- 26377845 TI - Dynameric asymmetric membranes for directional water transport. AB - Hydrophilic/hydrophobic dynamers prepared via template partial phase segregation have been used in the formation of asymmetric membranes for directional water transport. PMID- 26377846 TI - A Study of the 3,3,3-Trinitropropyl Unit as a Potential Energetic Building Block. AB - Compared with the well-established 2,2,2-trinitroethyl group in the chemistry of energetic materials, the 3,3,3-trinitropropyl group is less investigated regarding its chemical and energetic properties. Thus, investigations on the syntheses of several compounds containing the 3,3,3-trinitropropyl group were performed and their properties compared with the 2,2,2-trinitroethyl group. All materials were thoroughly characterized, including single-crystal X-ray diffraction studies. The thermal stabilities were examined using differential thermal analysis (DSC) and the sensitivities towards impact, friction, and electrostatic discharge were tested using a drop hammer, a friction tester, and an electrical discharge device. The energies of formation were calculated and several detonation parameters such as the velocity of detonation and the propulsion performance were estimated with the program package EXPLO5. PMID- 26377847 TI - Weight-reduction through a low-fat diet causes differential expression of circulating microRNAs in obese C57BL/6 mice. AB - BACKGROUND: To examine the circulating microRNA (miRNA) expression profile in a mouse model of diet-induced obesity (DIO) with subsequent weight reduction achieved via low-fat diet (LFD) feeding. RESULTS: Eighteen C57BL/6NCrl male mice were divided into three subgroups: (1) control, mice were fed a standard AIN-76A (fat: 11.5 kcal %) diet for 12 weeks; (2) DIO, mice were fed a 58 kcal % high-fat diet (HFD) for 12 weeks; and (3) DIO + LFD, mice were fed a HFD for 8 weeks to induce obesity and then switched to a 10.5 kcal % LFD for 4 weeks. A switch to LFD feeding led to decreases in body weight, adiposity, and blood glucose levels in DIO mice. Microarray analysis of miRNA using The Mouse & Rat miRNA OneArray(r) v4 system revealed significant alterations in the expression of miRNAs in DIO and DIO + LFD mice. Notably, 23 circulating miRNAs (mmu-miR-16, mmu-let-7i, mmu-miR 26a, mmu-miR-17, mmu-miR-107, mmu-miR-195, mmu-miR-20a, mmu-miR-25, mmu-miR-15b, mmu-miR-15a, mmu-let-7b, mmu-let-7a, mmu-let-7c, mmu-miR-103, mmu-let-7f, mmu-miR 106a, mmu-miR-106b, mmu-miR-93, mmu-miR-23b, mmu-miR-21, mmu-miR-30b, mmu-miR 221, and mmu-miR-19b) were significantly downregulated in DIO mice but upregulated in DIO + LFD mice. Target prediction and function annotation of associated genes revealed that these genes were predominantly involved in metabolic, insulin signaling, and adipocytokine signaling pathways that directly link the pathophysiological changes associated with obesity and weight reduction. CONCLUSIONS: These results imply that obesity-related reductions in the expression of circulating miRNAs could be reversed through changes in metabolism associated with weight reduction achieved through LFD feeding. PMID- 26377848 TI - Airway Exposure to E-Cigarette Vapors Impairs Autophagy and Induces Aggresome Formation. AB - AIMS: Electronic cigarettes (e-cigarettes) are proposed to be a safer alternative to tobacco cigarettes. Hence, we evaluated if e-cigarette vapors (eCV) impair cellular proteostasis similar to cigarette smoke exposure. RESULTS: First, we evaluated the impact of eCV exposure (2.5 or 7.5 mg) on Beas2b cells that showed significant increase in accumulation of total polyubiquitinated proteins (Ub, insoluble fractions) with time-dependent decrease in proteasomal activities from 1 h (p < 0.05), 3 h (p < 0.001) to 6 h (p < 0.001) of eCV exposure compared to room air control. We verified that even minimal eCV exposure (1 h) induces valosin-containing protein (VCP; p < 0.001), sequestosome-1/p62 (aberrant autophagy marker; p < 0.05), and aggresome formation (total poly-Ub-accumulation; p < 0.001) using immunoblotting (IB), fluorescence microscopy, and immunoprecipitation (IP). The inhibition of protein synthesis by 6 h of cycloheximide (50 MUg/ml) treatment significantly (p < 0.01) alleviates eCV induced (1 h) aggresome bodies. We also observed that eCV (1 h)-induced protein aggregation can activate oxidative stress, apoptosis (caspase-3/7), and senescence (p < 0.01) compared to room air controls. We verified using an autophagy inducer carbamazepine (20 MUM, 6 h) or cysteamine (250 MUM; 6 h, antioxidant) that eCV-induced changes in oxidative stress, poly-ub-accumulation, proteasomal activity, autophagy, apoptosis, and/or senescence could be controlled by autophagy induction. We further confirmed the role of acute eCV exposure on autophagy impairment in murine lungs (C57BL/6 and CD1) by IB (Ub, p62, VCP) and IP (VCP, p62), similar to in-vitro experiments. INNOVATION: In this study, we report for the first time that eCV exposure induces proteostasis/autophagy impairment leading to oxidative stress, apoptosis, and senescence that can be ameliorated by an autophagy inducer. CONCLUSION: eCV-induced autophagy impairment and aggresome formation suggest their potential role in chronic obstructive pulmonary disease-emphysema pathogenesis. Antioxid. Redox Signal. 00, 000-000. PMID- 26377849 TI - New insights on molecular regulation of biofilm formation in plant-associated bacteria. AB - Biofilms are complex bacterial assemblages with a defined three-dimensional architecture, attached to solid surfaces, and surrounded by a self-produced matrix generally composed of exopolysaccharides, proteins, lipids and extracellular DNA. Biofilm formation has evolved as an adaptive strategy of bacteria to cope with harsh environmental conditions as well as to establish antagonistic or beneficial interactions with their host. Plant-associated bacteria attach and form biofilms on different tissues including leaves, stems, vasculature, seeds and roots. In this review, we examine the formation of biofilms from the plant-associated bacterial perspective and detail the recently described mechanisms of genetic regulation used by these organisms to orchestrate biofilm formation on plant surfaces. In addition, we describe plant host signals that bacterial pathogens recognize to activate the transition from a planktonic lifestyle to multicellular behavior. PMID- 26377850 TI - Ordinary soap is as effective as antibacterial soap for handwashing, study finds. PMID- 26377851 TI - Psychiatric Conditions in Parkinson Disease: A Comparison With Classical Psychiatric Disorders. AB - Psychiatric conditions often complicate the outcome of patients affected by Parkinson disease (PD), but they differ from classical psychiatric disorders in terms of underlying biological mechanisms, clinical presentation, and treatment response. The purpose of the present review is to illustrate the biological and clinical aspects of psychiatric conditions associated with PD, with particular reference to the differences with respect to classical psychiatric disorders. A careful search of articles on main databases was performed in order to obtain a comprehensive review about the main psychiatric conditions associated with PD. A manual selection of the articles was then performed in order to consider only those articles that concerned with the topic of the review. Psychiatric conditions in patients with PD present substantial differences with respect to classical psychiatric disorders. Their clinical presentation does not align with the symptom profiles represented by Diagnostic and Statistical Manual for Mental Disorders and International Classification of Diseases. Furthermore, psychiatry treatment guidelines are of poor help in managing psychiatric symptoms of patients with PD. Specific diagnostic tools and treatment guidelines are needed to allow early diagnosis and adequate treatment of psychiatric conditions in comorbidity with PD. PMID- 26377853 TI - Hydrogen binding energies and electronic structure of Ni-Pd particles: a clue to their special catalytic properties. AB - We investigate the electronic structure of nickel-palladium systems with first principles density functional theory (DFT). Our study is motivated by the experimental observation that nickel-palladium nanoalloys containing approximately equal amounts of nickel and palladium show a higher catalytic activity in hydrogenation reactions than pure particles of either metal. Our calculations show that the energy with which hydrogen is bound to the metal surface, a decisive factor in catalytic activity, strongly depends on the nickel palladium ratio. The weakest binding and Gibbs free energies of hydrogen adsorption close to zero are found for systems with roughly equal amounts of nickel and palladium. While for extended Ni-Pd surfaces this observation can be explained by the well-established d-band model, for Ni-Pd clusters analysis of the electronic density of states shows a complex interplay of s- and d-orbital contributions. Studying extended surfaces further reveals that the formation of nanostructures on the surface can influence hydrogen adsorption pronouncedly. We discuss the important role that the exchange-correlation functional approximation plays in DFT calculations for nickel-palladium systems. PMID- 26377852 TI - Clinical Significance of Individual GAD Symptoms in Later Life. AB - BACKGROUND: There are age-related differences in the manifestation of generalized anxiety disorder (GAD) symptoms and their associated impact on psychosocial and functional status. However, it remains unclear whether specific symptoms (or symptom patterns) are of comparable clinical significance across different functional domains. METHODS: A sample of 865 self-reported worriers (aged 60 years and older) who endorsed GAD screening questions in the Alcohol Use Disorder and Associated Disabilities Interview Schedule, Diagnostic and Statistical Manual of Mental Disorders, fourth edition, were derived from Wave 1 of the National Epidemiological Survey of Alcohol and Related Conditions. RESULTS: Being easily fatigued was significantly associated with occupational disability and a functional disability variable (restricting usual activity in any way). Irritability was significantly associated with social friction (arguments with friends, family, or colleagues) and a functional disability variable (found was unable to do something wanted to do), and poor self-perceived health was also associated with the same functional disability variable. Excessive worry, despite being among the least reported symptoms, was significantly associated with distress. CONCLUSIONS: These findings suggest that individual GAD symptoms are differentially associated with aspects of clinical significance relevant to daily life, such as social, occupational, and functional ability. The differential impact of individual symptoms on functional status may be diluted when using symptom sum scores. A nuanced approach to assessing the clinical significance of individual GAD symptoms in older adults may be fruitful for efforts aimed at early detection and treatment. PMID- 26377854 TI - Different induction of LPA receptors by chemical liver carcinogens regulates cellular functions of liver epithelial WB-F344 cells. AB - Lysophosphatidic acid (LPA) signaling via LPA receptors (LPA1 to LPA6 ) mediates a variety of cellular functions, including cell motility. In the present study, we investigated the effects of LPA receptors on cell motile activity during multi stage hepatocarcinogenesis in rat liver epithelial WB-F344 cells treated with chemical liver carcinogens. Cells were treated with a initiator (N nitrosodiethylamine (DEN)) and three promoters (phenobarbital (PB), okadaic acid (OA) and clofibrate) every 24 h for 2 days. Cell motile activity was elevated by DEN, correlating with Lpar3 expression. PB, OA, and clofibrate elevated Lpar1 expression and inhibited cell motile activity. To evaluate the effects of long term treatment on cell motility, cells were treated with DEN and/or PB for at least 6 months. Lpar3 expression and cell motile activity were significantly elevated by the long-term DEN treatment with or without further PB treatment. In contrast, long-term PB treatment with or without further DEN elevated Lpar1 expression and inhibited cell motility. When the synthesis of extracellular LPA was blocked by a potent ATX inhibitor S32826 before cell motility assay, the cell motility induced by DEN and PB was markedly suppressed. These results suggest that activation of the different LPA receptors may regulate the biological functions of cells treated with chemical carcinogens. (c) 2015 Wiley Periodicals, Inc. PMID- 26377855 TI - Engineering cell-compatible paper chips for cell culturing, drug screening, and mass spectrometric sensing. AB - Paper-supported cell culture is an unprecedented development for advanced bioassays. This study reports a strategy for in vitro engineering of cell compatible paper chips that allow for adherent cell culture, quantitative assessment of drug efficiency, and label-free sensing of intracellular molecules via paper spray mass spectrometry. The polycarbonate paper is employed as an excellent alternative bioscaffold for cell distribution, adhesion, and growth, as well as allowing for fluorescence imaging without light scattering. The cell cultured paper chips are thus amenable to fabricate 3D tissue construction and cocultures by flexible deformation, stacks and assembly by layers of cells. As a result, the successful development of cell-compatible paper chips subsequently offers a uniquely flexible approach for in situ sensing of live cell components by paper spray mass spectrometry, allowing profiling the cellular lipids and quantitative measurement of drug metabolism with minimum sample pretreatment. Consequently, the developed paper chips for adherent cell culture are inexpensive for one-time use, compatible with high throughputs, and amenable to label-free and rapid analysis. PMID- 26377856 TI - The Effect of Hyperparathyroid State on Platelet Functions and Bone Loss. AB - OBJECTIVE: Coagulation and fibrinolysis defects were reported in primary hyperparathyroid patients. However, there are not enough data regarding platelet functions in this group of patients. Our aim was to evaluate the platelet functions in primary and secondary hyperparathyroid patients and to compare them with healthy subjects. MATERIALS AND METHODS: In our study 25 subjects with primary hyperparathyroidism (PHPT), 25 subjects with secondary hyperparathyroidism (SHPT), and 25 healthy controls were included. Platelet functions of the subjects were evaluated by using platelet-rich plasma and platelet aggregation tests induced with epinephrine, adenosine diphosphate (ADP), collagen, and ristocetin. Serum P selectin levels, which indicate platelet activation level, were measured in all subjects. Bone mineral densitometry was performed for all patients. RESULTS: There was no significant difference between the groups with PHPT and SHPT and the control group regarding the platelet aggregation tests and serum P selectin levels. There was also no significant correlation between parathormone levels and aggregation parameters (ristocetin, epinephrine, collagen, and ADP: respectively p=0.446, 0.537, 0.346, and 0.302) and between P selectin (p=0.516) levels. When we separated the patients according to serum calcium levels, there was also no significant difference between aggregation parameters and serum P selectin levels between the patients with hypercalcemia and the patients with normocalcemia. We could not find any significant correlation between aggregation parameters, P selectin levels, and serum calcium levels in this group of patients. Bone loss was greater in patients with PHPT. CONCLUSION: There is no significant effect of PHPT or SHPT and serum calcium levels on platelet functions when evaluated by aggregation tests. PMID- 26377857 TI - Climate Change, Extreme Weather Events, and Human Health Implications in the Asia Pacific Region. AB - The Asia Pacific region is regarded as the most disaster-prone area of the world. Since 2000, 1.2 billion people have been exposed to hydrometeorological hazards alone through 1215 disaster events. The impacts of climate change on meteorological phenomena and environmental consequences are well documented. However, the impacts on health are more elusive. Nevertheless, climate change is believed to alter weather patterns on the regional scale, giving rise to extreme weather events. The impacts from extreme weather events are definitely more acute and traumatic in nature, leading to deaths and injuries, as well as debilitating and fatal communicable diseases. Extreme weather events include heat waves, cold waves, floods, droughts, hurricanes, tropical cyclones, heavy rain, and snowfalls. Globally, within the 20-year period from 1993 to 2012, more than 530 000 people died as a direct result of almost 15 000 extreme weather events, with losses of more than US$2.5 trillion in purchasing power parity. PMID- 26377858 TI - 3D architecture constructed via the confined growth of MoS2 nanosheets in nanoporous carbon derived from metal-organic frameworks for efficient hydrogen production. AB - The design and synthesis of robust, high-performance and low-cost three dimensional (3D) hierarchical structured materials for the electrochemical reduction of water to generate hydrogen is of great significance for practical water splitting applications. In this study, we develop an in situ space-confined method to synthesize an MoS2-based 3D hierarchical structure, in which the MoS2 nanosheets grow in the confined nanopores of metal-organic frameworks (MOFs) derived 3D carbons as electrocatalysts for efficient hydrogen production. Benefiting from its unique structure, which has more exposed active sites and enhanced conductivity, the as-prepared MoS2/3D nanoporous carbon (3D-NPC) composite exhibits remarkable electrocatalytic activity for the hydrogen evolution reaction (HER) with a small onset overpotential of ~0.16 V, large cathodic currents, small Tafel slope of 51 mV per decade and good durability. We anticipate that this in situ confined growth provides new insights into the construction of high performance catalysts for energy storage and conversion. PMID- 26377860 TI - [Indications and surgical technique of subtotal hysterectomy for a general surgeon practicing in austere environment with limited resources]. AB - Uterine fibromyomata in Africa, which represents the most frequent benign uterine disease, is a real public health. This pathology is frequent and most of times discovered at a late stage where the volume of the uterus is responsible for invalidating symptoms that impairs patients' quality of life. Subtotal hysterectomy, which preserves the cervix, is faster than total hysterectomy and reduces intraoperative (duration of operation, blood loss) and postoperative morbidity (urinary infection, vaginal cicatrization). Subtotal hysterectomy is adapted to countries with limited resources. Its realization requires the preoperative assessment of normal cervix and a regular post-operative follow-up of the cervix left in place. PMID- 26377861 TI - Controversy and consensus regarding vitamin D: Recent methodological changes and the risks and benefits of vitamin D supplementation. AB - A dramatic and sustained surge in vitamin D test numbers has been attributed to the extraskeletal and probable intra/paracrine effects of vitamin D and not the important role of vitamin D in the regulation of extracellular calcium homeostasis and bone metabolism. This review summarizes recent data regarding the skeletal and extraskeletal effects of vitamin D, provides an overview of current methods of 25-hydroxyvitamin D measurement and includes the beneficial and adverse effects of vitamin D replacement. The role of 1,25-dihydroxyvitamin D, 24,25-dihydroxyvitamin D, vitamin D binding protein and free hormone levels are explored and potential future developments in this area are discussed. The adoption of a reference method for the measurement of 25-hydroxyvitamin D, certified reference standards and an independent certification program administered by the Centre of Disease Control is expected to improve routine analytical performance and is a major, crucial step forward. Improvements in accuracy, precision and sensitivity of 25-hydroxyvitamin D measurement is an important prelude to accurately defining the desirable level of 25-hydroxyvitamin D that is associated with the lowest risk for falls and fractures. Finally, the results of ongoing large, prospective, randomized clinical trials such as the Australian D-Health study should clarify the role of vitamin D supplementation in the prevention and management of skeletal and nonskeletal disorders, including vitamin D effects on mortality risk. PMID- 26377859 TI - Translational Regulation of the Mitochondrial Genome Following Redistribution of Mitochondrial MicroRNA in the Diabetic Heart. AB - BACKGROUND: Cardiomyocytes are rich in mitochondria which are situated in spatially distinct subcellular regions, including those under the plasma membrane, subsarcolemmal mitochondria, and those between the myofibrils, interfibrillar mitochondria. We previously observed subpopulation-specific differences in mitochondrial proteomes following diabetic insult. The objective of this study was to determine whether mitochondrial genome-encoded proteins are regulated by microRNAs inside the mitochondrion and whether subcellular spatial location or diabetes mellitus influences the dynamics. METHODS AND RESULTS: Using microarray technology coupled with cross-linking immunoprecipitation and next generation sequencing, we identified a pool of mitochondrial microRNAs, termed mitomiRs, that are redistributed in spatially distinct mitochondrial subpopulations in an inverse manner following diabetic insult. Redistributed mitomiRs displayed distinct interactions with the mitochondrial genome requiring specific stoichiometric associations with RNA-induced silencing complex constituents argonaute-2 (Ago2) and fragile X mental retardation-related protein 1 (FXR1) for translational regulation. In the presence of Ago2 and FXR1, redistribution of mitomiR-378 to the interfibrillar mitochondria following diabetic insult led to downregulation of mitochondrially encoded F0 component ATP6. Next generation sequencing analyses identified specific transcriptome and mitomiR sequences associated with ATP6 regulation. Overexpression of mitomiR-378 in HL-1 cells resulted in its accumulation in the mitochondrion and downregulation of functional ATP6 protein, whereas antagomir blockade restored functional ATP6 protein and cardiac pump function. CONCLUSIONS: We propose mitomiRs can translationally regulate mitochondrially encoded proteins in spatially distinct mitochondrial subpopulations during diabetes mellitus. The results reveal the requirement of RNA-induced silencing complex constituents in the mitochondrion for functional mitomiR translational regulation and provide a connecting link between diabetic insult and ATP synthase function. PMID- 26377862 TI - Antimicrobial resistance: moving from professional engagement to public action. AB - Antimicrobial-resistant infections claim >=700 000 lives each year globally. It is therefore important that both healthcare professionals and the public know the threat antimicrobial resistance poses and the individual actions they can take to combat antimicrobial resistance. Antibiotic awareness campaigns in England using posters or leaflets have had little or no impact on knowledge, behaviour or prescription rates. Centrally coordinated, multimodal campaigns in two European countries (ongoing for several years and including print and mass media, web site and guidelines, as well as academic detailing and individual feedback to prescribers) have led to reductions in antibiotic use. To change behaviour and reduce antibiotic use in England, a coordinated and comprehensive interdisciplinary and multifaceted (multimodal) approach using behavioural science and targeted at specific groups (both professional and public) is required. Such campaigns should have an integrated evaluation plan using a combination of formative, process and summative measures from the outset to completion of a campaign. PMID- 26377863 TI - Low prevalence of mupirocin resistance in Belgian Staphylococcus aureus isolates collected during a 10 year nationwide surveillance. PMID- 26377864 TI - Antimicrobial susceptibility testing breakpoints and methods from BSAC to EUCAST. AB - The BSAC Standing Committee on Antimicrobial Susceptibility Testing is one of several European national breakpoint committees that agreed in 2002 to harmonize clinical MIC breakpoints. The process of harmonization has since been completed for commonly used agents, and breakpoints for new agents have been set by EUCAST in accordance with a procedure defined by the EMA. EUCAST breakpoints have now been adopted by a large majority of laboratories in Europe. BSAC implemented the EUCAST breakpoints in its own disc diffusion susceptibility testing method as harmonized breakpoints were agreed to over the years. Since the development of the EUCAST disc diffusion method, several countries with their own disc diffusion methods have switched to the EUCAST method, and BSAC will replace support of its own disc diffusion method with support for the EUCAST method from January 2016. The EUCAST breakpoints are also available in automated systems. The harmonized breakpoints and methods will help to avoid different reports of susceptibility for the same isolate in different countries and enable more reliable comparison of resistance rates in surveillance studies in different countries. PMID- 26377865 TI - Carbapenemase-producing Salmonella enterica serotype Kentucky ST198, North Africa. PMID- 26377867 TI - In response. PMID- 26377866 TI - Novel transferable erm(46) determinant responsible for emerging macrolide resistance in Rhodococcus equi. AB - OBJECTIVES: The objective of this study was to identify the molecular mechanism of macrolide resistance in the actinomycete Rhodococcus equi, a major equine pathogen and zoonotic agent causing opportunistic infections in people. METHODS: Macrolide-resistant (n = 62) and macrolide-susceptible (n = 62) clinical isolates of R. equi from foals in the USA were studied. WGS of 18 macrolide-resistant and 6 macrolide-susceptible R. equi was performed. Representative sequences of all known macrolide resistance genes identified to date were used to search the genome assemblies for putative homologues. PCR was used to screen for the presence of the identified resistance determinant in the rest of the isolates. Mating experiments were performed to verify mobility of the gene. RESULTS: A novel erm gene, erm(46), was identified in all sequenced resistant isolates, but not in susceptible isolates. There was complete association between macrolide resistance and the presence of erm(46) as detected by PCR screening of all 124 clinical isolates of R. equi. Expression of erm(46) in a macrolide-susceptible strain of R. equi induced high-level resistance to macrolides, lincosamides and streptogramins B, but not to other classes of antimicrobial agents. Transfer of erm(46) to macrolide-susceptible R. equi was confirmed. The transfer frequency ranged from 3 * 10(-3) to 1 * 10(-2). CONCLUSIONS: This is the first molecular characterization of resistance to macrolides, lincosamides and streptogramins B in R. equi. Resistance was due to the presence of a novel erm(46) gene mobilizable likely by conjugation, which has spread among equine isolates of R. equi in the USA. PMID- 26377868 TI - Minimization or withdrawal of immunosuppressants in pediatric liver transplant recipients. AB - BACKGROUND: We aimed to minimize the dose of tacrolimus in pediatric patients undergoing liver transplantation prospectively. METHODS: Pediatric liver transplant recipients with stable graft function >1year (transplant at <1year of age), or 2years (transplant at >1year of age) post transplant were screened. After baseline graft biopsy, patients were enrolled into our protocol for elective tacrolimus dose reduction. Patients were assessed by liver function test and protocol biopsy during and after tacrolimus dose reduction. RESULTS: From January 2011 to December 2012, 16 patients were recruited, of whom 15 completed follow-up at a mean 40.75+/-5.98months. Six patients were preliminarily weaned off tacrolimus, and five remained tacrolimus-free for more than 2years. Of the 10 patients who were not weaned off tacrolimus, six experienced seven episodes of clinical rejection. Five patients had a reduction in tacrolimus dosage to an undetectable trough level, another five to a trough level <4ng/ml, including one patient who was off the study. At the last patient visit, all of the patients had normal liver function test results with no graft loss. Three patients had low grade graft fibrosis. The patients with metabolic liver disease (p=0.039) and who were recruited earlier after transplantation (p=0.028) were more likely to be weaned off tacrolimus. CONCLUSION: Tacrolimus withdrawal is feasible in select pediatric liver transplant recipients, and long-term follow-up for these patients is suggested. PMID- 26377869 TI - Is complete resection of high-risk stage IV neuroblastoma associated with better survival? AB - BACKGROUND: The role of surgery in the management of stage IV neuroblastoma is controversial. In this study, we attempted to study if complete tumor resection had any impact on event-free survival (EFS) and overall survival (OS). METHODS: A retrospective analysis of patients with stage IV neuroblastoma between November 2000 and July 2014 in a tertiary referral center was performed. Demographics data, extent of surgical resection, and outcomes were analyzed. RESULTS: A total of 34 patients with stage IV neuroblastoma according to International Neuroblastoma Staging System (INSS) were identified. The median age at diagnosis and operation was 3.5 (+/-1.9) years and 3.8 (+/-2.0) years, respectively. Complete gross tumor resection (CTR) was achieved in twenty-four patients (70.1%), in which one of the patients had nephrectomy and another had distal pancreatectomy. Gross total resection (GTR) with removal of >95% of tumor was performed in six patients (17.6%) and subtotal tumor resection (STR) with removal of >50%, but <95% of tumor was performed in four patients (11.8%). There was no statistical significance in terms of 5-year EFS and OS among the 3 groups. There was no surgery-related mortality or morbidity. CONCLUSIONS: From our center's experience, as there was no substantial survival benefit in stage IV neuroblastoma patients undergoing complete tumor resection, organ preservation and minimalization of morbidity should also be taken into consideration. PMID- 26377870 TI - Effect of diet-derived advanced glycation end products on inflammation. AB - Advanced glycation end products (AGEs) formed via the Maillard reaction during the thermal processing of food contributes to the flavor, color, and aroma of food. A proportion of food-derived AGEs and their precursors is intestinally absorbed and accumulates within cells and tissues. AGEs have been implicated in the pathogenesis of diabetes-related complications and several chronic diseases via interaction with the receptor for AGEs, which promotes the transcription of genes that control inflammation. The dicarbonyls, highly reactive intermediates of AGE formation, are also generated during food processing and may incite inflammatory responses through 1) the suppression of protective pathways, 2) the incretin axis, 3) the modulation of immune-mediated signaling, and 4) changes in gut microbiota profile and metabolite sensors. In animal models, restriction of dietary AGEs attenuates chronic low-grade inflammation, but current evidence from human studies is less clear. Here, the emerging relationship between excess dietary AGE consumption and inflammation is explored, the utility of dietary AGE restriction as a therapeutic strategy for the attenuation of chronic diseases is discussed, and possible avenues for future investigation are suggested. PMID- 26377871 TI - Divergent climate response on hydraulic-related xylem anatomical traits of Picea abies along a 900-m altitudinal gradient. AB - Climate change can induce substantial modifications in xylem structure and water transport capacity of trees exposed to environmental constraints. To elucidate mechanisms of xylem plasticity in response to climate, we retrospectively analysed different cell anatomical parameters over tree-ring series in Norway spruce (Picea abies L. Karst.). We sampled 24 trees along an altitudinal gradient (1200, 1600 and 2100 m above sea level, a.s.l.) and processed 2335 +/- 1809 cells per ring. Time series for median cell lumen area (MCA), cell number (CN), tree ring width (RW) and tree-ring-specific hydraulic conductivity (Kr) were crossed with daily temperature and precipitation records (1926-2011) to identify climate influence on xylem anatomical traits. Higher Kr at the low elevation site was due to higher MCA and CN. These variables were related to different aspects of intra seasonal climatic variability under different environmental conditions, with MCA being more sensitive to summer precipitation. Winter precipitation (snow) benefited most parameters in all the sites. Descending the gradient, sensitivity of xylem features to summer climate shifted mostly from temperature to precipitation. In the context of climate change, our results indicate that higher summer temperatures at high elevations will benefit cell production and xylem hydraulic efficiency, whereas reduced water availability at lower elevations could negatively affect tracheids enlargement and thus stem capacity to transport water. PMID- 26377872 TI - Low among-provenance differences in structural and functional plasticity in response to nutrients in saplings of the circum-Mediterranean tree Arbutus unedo L. AB - The Mediterranean region is an area of special interest for conservation where the incidence of multiple drivers of global change is expected to increase. One of the factors predicted to change is soil-nutrient availability, an essential factor for plant growth. Thus, study of the effects of variation in this parameter is especially relevant in species with a circum-Mediterranean distribution, such as Arbutus unedo L., in which the different provenances grow in different habitats, which must differ in nutritional conditions. We aimed to determine the effect of provenance on plasticity, to establish whether structural and morphological traits differ in the level of plasticity and to assess how nutrients affect the photosynthetic light response. In a common garden experiment, we studied seven provenances from the circum-Mediterranean range of A. unedo and established two nutrient treatments (low and high nutrient availability). We measured physiological and structural traits in 1-year-old sapling and determined a phenotypic plasticity index (PPI) to quantify the level of plasticity, whereas the radiation effects were tested by construction and analysis of light response curves. Interestingly, provenance did not explain a significant amount of variance, but the plasticity was four times higher for the structural traits than for the physiological traits. Therefore, the plasticity to nutrient availability will not favour or prevent the expansion or contraction of the range of any of these provenances of A. unedo. Furthermore, the structural plasticity demonstrated the ability of the strawberry tree to optimize resource allocation, whereas the physiology remained stable, thus avoiding extra expenditure. The study findings also suggest that increased availability of nutrients would improve the performance of the species during the Mediterranean summer, characterized by high irradiance. These abilities will be key to the survival of saplings of the species under the future scenario of changes in nutrient availability. PMID- 26377873 TI - Growth cessation uncouples isotopic signals in leaves and tree rings of drought exposed oak trees. AB - An increase in temperature along with a decrease in summer precipitation in Central Europe will result in an increased frequency of drought events and gradually lead to a change in species composition in forest ecosystems. In the present study, young oaks (Quercus robur L. and Quercus petraea (Matt.) Liebl.) were transplanted into large mesocosms and exposed for 3 years to experimental warming and a drought treatment with yearly increasing intensities. Carbon and oxygen isotopic (delta(13)C and delta(18)O) patterns were analysed in leaf tissue and tree-ring cellulose and linked to leaf physiological measures and tree-ring growth. Warming had no effect on the isotopic patterns in leaves and tree rings, while drought increased delta(18)O and delta(13)C. Under severe drought, an unexpected isotopic pattern, with a decrease in delta(18)O, was observed in tree rings but not in leaves. This decrease in delta(18)O could not be explained by concurrent physiological analyses and is not supported by current physiological knowledge. Analysis of intra-annual tree-ring growth revealed a drought-induced growth cessation that interfered with the record of isotopic signals imprinted on recently formed leaf carbohydrates. This missing record indicates isotopic uncoupling of leaves and tree rings, which may have serious implications for the interpretation of tree-ring isotopes, particularly from trees that experienced growth-limiting stresses. PMID- 26377874 TI - Synchronisms and correlations of spring phenology between apical and lateral meristems in two boreal conifers. AB - Phenological synchronisms between apical and lateral meristems could clarify some aspects related to the physiological relationships among the different organs of trees. This study correlated the phenological phases of bud development and xylem differentiation during spring 2010-14 in balsam fir (Abies balsamea Mill.) and black spruce [(Picea mariana Mill. (BSP)] of the Monts-Valin National Park (Quebec, Canada) by testing the hypothesis that bud development occurs after the reactivation of xylem growth. From May to September, we conducted weekly monitoring of xylem differentiation using microcores and bud development with direct observations on terminal branches. Synchronism between the beginning of bud development and xylem differentiation was found in both species with significant correlations between the phases of bud and xylem phenology. Degree day sum was more appropriate in assessing the date of bud growth resumption, while thermal thresholds were more suitable for cambium phenology. Our results provide new knowledge on the dynamics of spring phenology and novel information on the synchronisms between two meristems in coniferous trees. The study demonstrates the importance of precisely defining the phases of bud development in order to correctly analyse the relationships with xylem phenology. PMID- 26377875 TI - Stem diameter variations as a versatile research tool in ecophysiology. AB - High-resolution stem diameter variations (SDV) are widely recognized as a useful drought stress indicator and have therefore been used in many irrigation scheduling studies. More recently, SDV have been used in combination with other plant measurements and biophysical modelling to study fundamental mechanisms underlying whole-plant functioning and growth. The present review aims to scrutinize the important insights emerging from these more recent SDV applications to identify trends in ongoing fundamental research. The main mechanism underlying SDV is variation in water content in stem tissues, originating from reversible shrinkage and swelling of dead and living tissues, and irreversible growth. The contribution of different stem tissues to the overall SDV signal is currently under debate and shows variation with species and plant age, but can be investigated by combining SDV with state-of-the-art technology like magnetic resonance imaging. Various physiological mechanisms, such as water and carbon transport, and mechanical properties influence the SDV pattern, making it an extensive source of information on dynamic plant behaviour. To unravel these dynamics and to extract information on plant physiology or plant biophysics from SDV, mechanistic modelling has proved to be valuable. Biophysical models integrate different mechanisms underlying SDV, and help us to explain the resulting SDV signal. Using an elementary modelling approach, we demonstrate the application of SDV as a tool to examine plant water relations, plant hydraulics, plant carbon relations, plant nutrition, freezing effects, plant phenology and dendroclimatology. In the ever-expanding SDV knowledge base we identified two principal research tracks. First, in detailed short-term experiments, SDV measurements are combined with other plant measurements and modelling to discover patterns in phloem turgor, phloem osmotic concentrations, root pressure and plant endogenous control. Second, long-term SDV time series covering many different species, regions and climates provide an expanding amount of phenotypic data of growth, phenology and survival in relation to microclimate, soil water availability, species or genotype, which can be coupled with genetic information to support ecological and breeding research under on-going global change. This under-exploited source of information has now encouraged research groups to set up coordinated initiatives to explore this data pool via global analysis techniques and data-mining. PMID- 26377876 TI - Stem compression reversibly reduces phloem transport in Pinus sylvestris trees. AB - Manipulating tree belowground carbon (C) transport enables investigation of the ecological and physiological roles of tree roots and their associated mycorrhizal fungi, as well as a range of other soil organisms and processes. Girdling remains the most reliable method for manipulating this flux and it has been used in numerous studies. However, girdling is destructive and irreversible. Belowground C transport is mediated by phloem tissue, pressurized through the high osmotic potential resulting from its high content of soluble sugars. We speculated that phloem transport may be reversibly blocked through the application of an external pressure on tree stems. Thus, we here introduce a technique based on compression of the phloem, which interrupts belowground flow of assimilates, but allows trees to recover when the external pressure is removed. Metal clamps were wrapped around the stems and tightened to achieve a pressure theoretically sufficient to collapse the phloem tissue, thereby aiming to block transport. The compression's performance was tested in two field experiments: a (13)C canopy labelling study conducted on small Scots pine (Pinus sylvestris L.) trees [2-3 m tall, 3-7 cm diameter at breast height (DBH)] and a larger study involving mature pines (~15 m tall, 15-25 cm DBH) where stem respiration, phloem and root carbohydrate contents, and soil CO2 efflux were measured. The compression's effectiveness was demonstrated by the successful blockage of (13)C transport. Stem compression doubled stem respiration above treatment, reduced soil CO2 efflux by 34% and reduced phloem sucrose content by 50% compared with control trees. Stem respiration and soil CO2 efflux returned to normal within 3 weeks after pressure release, and (13)C labelling revealed recovery of phloem function the following year. Thus, we show that belowground phloem C transport can be reduced by compression, and we also demonstrate that trees recover after treatment, resuming C transport in the phloem. PMID- 26377877 TI - Polymer Electrolyte Membrane Electrolyzers Utilizing Non-precious Mo-based Hydrogen Evolution Catalysts. AB - The development of low-cost hydrogen evolution reaction (HER) catalysts that can be readily integrated into electrolyzers is critical if H2 from renewable electricity-powered electrolysis is to compete cost effectively with steam reforming. Herein, we report three distinct earth-abundant Mo-based catalysts, namely those based on MoSx , [Mo3 S13 ](2-) nanoclusters, and sulfur-doped Mo phosphide (MoP|S), loaded onto carbon supports. The catalysts were synthesized through facile impregnation-sulfidization routes specifically designed for catalyst-device compatibility. Fundamental electrochemical studies demonstrate the excellent HER activity and stability of the Mo-sulfide based catalysts in an acidic environment, and the resulting polymer electrolyte membrane (PEM) electrolyzers that integrate these catalysts exhibit high efficiency and durability. This work is an important step towards the goal of replacing Pt with earth-abundant catalysts for the HER in commercial PEM electrolyzers. PMID- 26377889 TI - Evaluating Manifest Monotonicity Using Bayes Factors. AB - The assumption of latent monotonicity in item response theory models for dichotomous data cannot be evaluated directly, but observable consequences such as manifest monotonicity facilitate the assessment of latent monotonicity in real data. Standard methods for evaluating manifest monotonicity typically produce a test statistic that is geared toward falsification, which can only provide indirect support in favor of manifest monotonicity. We propose the use of Bayes factors to quantify the degree of support available in the data in favor of manifest monotonicity or against manifest monotonicity. Through the use of informative hypotheses, this procedure can also be used to determine the support for manifest monotonicity over substantively or statistically relevant alternatives to manifest monotonicity, rendering the procedure highly flexible. The performance of the procedure is evaluated using a simulation study, and the application of the procedure is illustrated using empirical data. PMID- 26377890 TI - Robot-assisted single-site upper pole hemi-nephrectomy in an adult patient with a duplicated collecting system: is it feasible? PMID- 26377891 TI - Stressed-Out Endoplasmic Reticulum Inflames the Mitochondria. AB - Bacterial infection induces inflammasome activation and release of interleukin-1 (IL-1) cytokines. Bronner et al. (2015) show that during Brucella abortus infection, an endoplasmic reticulum stress sensor, IRE1alpha, initiates NLRP3- and caspase-2-mediated mitochondrial damage that potentiates NLRP3 inflammasome assembly. PMID- 26377892 TI - Exonuclease TREX1 also Has a Sweet Tooth. AB - TREX1 regulates innate immune responses by counteracting DNA accumulation in the cytosol. In this issue of Immunity, Hasan et al. (2015) show that TREX1 also safeguards the cell against free glycan build-up in the endoplasmic reticulum, thereby preventing glycan-induced inflammation. PMID- 26377893 TI - IL-17A Has Some Nerve! AB - Sensory neurons are important in controlling cutaneous inflammation, but the role of neurons in host antimicrobial defense was relatively unknown. Kaplan and colleagues now demonstrate that nociceptive fibers within the dermis play a crucial role in antifungal defenses through their influence on dermal dendritic cells and induction of IL-17A. PMID- 26377894 TI - Independence Day for IgA. AB - IgA is induced through T-cell-dependent and -independent pathways. In this issue, Bunker et al. (2015) now show that the T-cell-independent pathway is sufficient to coat most small intestinal microbes specifically, and Fransen et al. (2015) find that IgA coating promotes uptake of microbes into Peyer's patches and drives further induction in a positive-feedback loop. PMID- 26377895 TI - Close Encounters of the Tertiary Kind. AB - Elucidating the function of tumor-infiltrating regulatory T (Treg) cells has been difficult. In this issue of Immunity, Joshi et al. (2015) demonstrate that Treg cells associated with murine lung cancers are found within tertiary lymphoid structures and actively restrain effector T cells at the tumor site. PMID- 26377896 TI - The Cellular and Molecular Basis of Translational Immunometabolism. AB - The immune response requires major changes to metabolic processes, and indeed, energy metabolism and functional activation are fully integrated in immune cells to determine their ability to divide, differentiate, and carry out effector functions. Immune cell metabolism has therefore become an attractive target area for therapeutic purposes. A neglected aspect in the translation of immunometabolism is the critical connection between systemic and cellular metabolism. Here, we discuss the importance of understanding and manipulating the integration of systemic and immune cell metabolism through in-depth analysis of immune cell phenotype and function in human metabolic diseases and, in parallel, of the effects of conventional metabolic drugs on immune cell differentiation and function. We examine how the recent identification of selective metabolic programs operating in distinct immune cell subsets and functions has the potential to deliver tools for cell- and function-specific immunometabolic targeting. PMID- 26377897 TI - Metabolic Reprogramming of Immune Cells in Cancer Progression. AB - Immune cells play a key role in host defense against infection and cancer. Upon encountering danger signals, these cells undergo activation leading to a modulation in their immune functions. However, recent studies reveal that immune cells upon activation also show distinct metabolic changes that impact their immune functions. Such metabolic reprogramming and its functional effects are well known for cancer cells. Given that immune cells have emerged as crucial players in cancer progression, it is important to understand whether immune cells also undergo metabolic reprogramming in tumors and how this might affect their contribution in cancer progression. This emerging aspect of tumor-associated immune cells is reviewed here, discussing metabolic reprogramming of different immune cell types, the key pathways involved, and its impact on tumor progression. PMID- 26377899 TI - Neural correlates of interactions between cannabidiol and Delta(9) tetrahydrocannabinol in mice: implications for medical cannabis. AB - BACKGROUND AND PURPOSE: It has been proposed that medicinal strains of cannabis and therapeutic preparations would be safer with a more balanced concentration ratio of Delta(9) -tetrahydrocannabinol (THC) to cannabidiol (CBD), as CBD reduces the adverse psychotropic effects of THC. However, our understanding of CBD and THC interactions is limited and the brain circuitry mediating interactions between CBD and THC are unknown. The aim of this study was to investigate whether CBD modulated the functional effects and c-Fos expression induced by THC, using a 1:1 dose ratio that approximates therapeutic strains of cannabis and nabiximols. EXPERIMENTAL APPROACH: Male C57BL/6 mice were treated with vehicle, CBD, THC or a combination of CBD and THC (10 mg.kg(-1) i.p. for both cannabinoids) to examine effects on locomotor activity, anxiety-related behaviour, body temperature and brain c-Fos expression (a marker of neuronal activation). KEY RESULTS: CBD potentiated THC-induced locomotor suppression but reduced the hypothermic and anxiogenic effects of THC. CBD alone had no effect on these measures. THC increased brain activation as measured by c-Fos expression in 11 of the 35 brain regions studied. CBD co-administration suppressed THC-induced c-Fos expression in six of these brain regions. This effect was most pronounced in the medial preoptic nucleus and lateral periaqueductal gray. Treatment with CBD alone diminished c-Fos expression only in the central nucleus of the amygdala compared with vehicle. CONCLUSIONS AND IMPLICATIONS: These data confirm that CBD modulated the pharmacological actions of THC and provide new information regarding brain regions involved in the interaction between CBD and THC. PMID- 26377898 TI - Nociceptive Sensory Fibers Drive Interleukin-23 Production from CD301b+ Dermal Dendritic Cells and Drive Protective Cutaneous Immunity. AB - Innate resistance to Candida albicans in mucosal tissues requires the production of interleukin-17A (IL-17A) by tissue-resident cells early during infection, but the mechanism of cytokine production has not been precisely defined. In the skin, we found that dermal gammadelta T cells were the dominant source of IL-17A during C. albicans infection and were required for pathogen resistance. Induction of IL 17A from dermal gammadelta T cells and resistance to C. albicans required IL-23 production from CD301b(+) dermal dendritic cells (dDCs). In addition, we found that sensory neurons were directly activated by C. albicans. Ablation of sensory neurons increased susceptibility to C. albicans infection, which could be rescued by exogenous addition of the neuropeptide CGRP. These data define a model in which nociceptive pathways in the skin drive production of IL-23 by CD301b(+) dDCs resulting in IL-17A production from gammadelta T cells and resistance to cutaneous candidiasis. PMID- 26377902 TI - Defibrillator lead endocarditis. PMID- 26377901 TI - Direct comparison of cardiac magnetic resonance feature tracking and 2D/3D echocardiography speckle tracking for evaluation of global left ventricular strain. AB - AIMS: Cardiac magnetic resonance (CMR) feature tracking (FT) with steady-state free precession (SSFP) has advantages over traditional myocardial tagging to analyse left ventricular (LV) strain. However, direct comparisons of CMRFT and 2D/3D echocardiography speckle tracking (2/3DEST) for measurement of LV strain are limited. The aim of this study was to investigate the feasibility and reliability of CMRFT and 2D/3DEST for measurement of global LV strain. METHODS AND RESULTS: We enrolled 106 patients who agreed to undergo both CMR and 2D/3DE on the same day. SSFP images at multiple short-axis and three apical views were acquired. 2DE images from three levels of short-axis, three apical views, and 3D full-volume datasets were also acquired. Strain data were expressed as absolute values. Feasibility was highest in CMRFT, followed by 2DEST and 3DEST. Analysis time was shortest in 3DEST, followed by CMRFT and 2DEST. There was good global longitudinal strain (GLS) correlation between CMRFT and 2D/3DEST (r = 0.83 and 0.87, respectively) with the limit of agreement (LOA) ranged from +/-3.6 to +/ 4.9%. Excellent global circumferential strain (GCS) correlation between CMRFT and 2D/3DEST was observed (r = 0.90 and 0.88) with LOA of +/-6.8-8.5%. Global radial strain showed fair correlations (r = 0.69 and 0.82, respectively) with LOA ranged from +/-12.4 to +/-16.3%. CMRFT GCS showed least observer variability with highest intra-class correlation. CONCLUSION: Although not interchangeable, the high GLS and GCS correlation between CMRFT and 2D/3DEST makes CMRFT a useful modality for quantification of global LV strain in patients, especially those with suboptimal echo image quality. PMID- 26377903 TI - The year 2014 in the European Heart Journal--Cardiovascular Imaging: part II. AB - The European Heart Journal-Cardiovascular Imaging, created in 2012, has become a reference for publishing multimodality cardiovascular imaging scientific and review papers. The impressive 2014 impact factor of 4.105 confirms the important position of our journal. In this part, we summarize the most important studies from the journal's third year, with specific emphasis on cardiomyopathies, congenital heart diseases, valvular heart diseases, and heart failure. PMID- 26377900 TI - Malaria endemicity and co-infection with tissue-dwelling parasites in Sub-Saharan Africa: a review. AB - Mechanisms and outcomes of host-parasite interactions during malaria co infections with gastrointestinal helminths are reasonably understood. In contrast, very little is known about such mechanisms in cases of malaria co infections with tissue-dwelling parasites. This is lack of knowledge is exacerbated by misdiagnosis, lack of pathognomonic clinical signs and the chronic nature of tissue-dwelling helminthic infections. A good understanding of the implications of tissue-dwelling parasitic co-infections with malaria will contribute towards the improvement of the control and management of such co infections in endemic areas. This review summarises and discusses current information available and gaps in research on malaria co-infection with gastro intestinal helminths and tissue-dwelling parasites with emphasis on helminthic infections, in terms of the effects of migrating larval stages and intra and extracellular localisations of protozoan parasites and helminths in organs, tissues, and vascular and lymphatic circulations. PMID- 26377905 TI - The role of early contrast-enhanced chest computed tomography in the aetiological diagnosis of patients presenting with cardiac tamponade or large pericardial effusion. AB - AIMS: The role of chest computed tomography (CT) is not well defined for either diagnosis or management of pericardial disease. The aim of this study was to evaluate the added value of early chest CT in the diagnostic workup for patients presenting with cardiac tamponade or large pericardial effusion of unknown aetiology as the first manifestation of disease. METHODS AND RESULTS: We performed CT scan on 55 patients with pericardial effusion as defined above, undergoing echo-guided pericardiocentesis. We compared the success rate in making diagnosis and/or staging the underlying disorder of three sequential workups, including, respectively, (i) clinical presentation, inflammatory markers, chest X ray imaging, (ii) all of the above and pericardial fluid analysis, and (iii) all of the above and chest CT. We were able to make diagnosis in 53 patients (96%): the major cause of effusion was malignancy (38%). Clinical and biochemical data were not able to differentiate non-tumour from tumour patients. CT revealed pathological findings in all patients with malignancy: tumour mass in 15/21 (71%) and pathological lymphadenopathy in the remaining 6 cases. The workup including CT provided a significantly higher diagnostic yield than the other two workups (P < 0.0001), both in the overall population and in the two subgroups of neoplastic (Npl) and non-Npl patients. CONCLUSION: In all patients with cardiac tamponade or large pericardial effusion, CT was useful either in identifying the underlying disease or in excluding other potential causes of pericardial effusion. We conclude that chest CT is a very useful non-invasive diagnostic tool to identify and stage pericardial diseases. PMID- 26377904 TI - Multi-laboratory inter-institute reproducibility study of IVOCT and IVUS assessments using published consensus document definitions. AB - AIMS: The aim of this study was to investigate the reproducibility of intravascular optical coherence tomography (IVOCT) assessments, including a comparison to intravascular ultrasound (IVUS). Intra-observer and inter-observer variabilities of IVOCT have been previously described, whereas inter-institute reliability in multiple laboratories has never been systematically studied. METHODS AND RESULTS: In 2 independent laboratories with intravascular imaging expertise, 100 randomized matched data sets of IVOCT and IVUS images were analysed by 4 independent observers according to published consensus document definitions. Intra-observer, inter-observer, and inter-institute variabilities of IVOCT qualitative and quantitative measurements vs. IVUS measurements were assessed. Minor inter- and intra-observer variability of both imaging techniques was observed for detailed qualitative and geometric analysis, except for inter observer mixed plaque identification on IVUS (kappa = 0.70) and for inter observer fibrous cap thickness measurement reproducibility on IVOCT (ICC = 0.48). The magnitude of inter-institute measurement differences for IVOCT was statistically significantly less than that for IVUS concerning lumen cross sectional area (CSA), maximum and minimum lumen diameters, stent CSA, and maximum and minimum stent diameters (P < 0.001, P < 0.001, P < 0.001, P = 0.02, P < 0.001, and P = 0.01, respectively). Minor inter-institute measurement variabilities using both techniques were also found for plaque identification. CONCLUSION: In the measurement of lumen CSA, maximum and minimum lumen diameters, stent CSA, and maximum and minimum stent diameters by analysts from two different laboratories, reproducibility of IVOCT was more consistent than that of IVUS. PMID- 26377906 TI - Coronary healing after stenting: wounds, faith, and the quest for the perfect stent. PMID- 26377907 TI - PROMISE: where now for CT coronary angiography. PMID- 26377908 TI - Four-dimensional flow magnetic resonance imaging-based characterization of aortic morphometry and haemodynamics: impact of age, aortic diameter, and valve morphology. AB - AIMS: Four-dimensional (4D) flow magnetic resonance imaging (MRI) was employed for the simultaneous assessment of morphometry and flow parameters along the thoracic aorta to investigate associations between flow, age, aorta diameter, and aortic valve morphology. METHODS AND RESULTS: One hundred and sixty-five subjects, 65 controls, 50 patients with bicuspid aortic valve (BAV), and 50 patients with a dilated aorta, and a tricuspid aortic valve (TAV) underwent 4D flow MRI. Following 3D segmentation of the aorta, a vessel centreline was calculated and used to extract aorta diameter, peak systolic velocity, and normalized systolic flow displacement. Validation of 4D flow MRI-based morphometric measurements compared with manual diameter measurements from standard contrast-enhanced MR angiography in 20 controls showed good agreement (mean difference = 0.4 mm, limits of agreement = +/-1.31 mm) except at the sinus of valsalva. BAV showed significant differences in average peak velocity (PV; P < 0.016) compared with TAV and controls between the left ventricle outflow tract to sino-tubular junction (BAV: 1.3 +/- 0.3 m/s; TAV: 1.2 +/- 0.2 m/s; controls: 1.0 +/- 0.1 m/s) and the ascending aorta for average normalized flow displacement (BAV: 0.11 +/- 0.02; TAV: 0.09 +/- 0.02; controls: 0.06 +/- 0.01, P < 0.016) despite similar average aortic dimensions for BAV (37 +/- 1 mm) and TAV (39 +/- 1 mm). Multivariate linear regression showed a significant correlation of maximal aortic diameter to age, PV, and normalized flow displacement (R(2) = 0.413, P < 0.001). CONCLUSION: A single acquisition of 4D flow MRI characterized local morphological and haemodynamic differences between groups along the aorta. BAV showed altered haemodynamics when compared with TAV in spite of having similar aorta dimensions. Maximal aorta diameter was associated with age, PV, and normalized flow displacement. PMID- 26377909 TI - Randomised trial of neonatal hypoglycaemia prevention with oral dextrose gel (hPOD): study protocol. AB - BACKGROUND: Neonatal hypoglycaemia is common, affecting up to 15% of newborn babies and 50% of those with risk factors (preterm, infant of a diabetic, high or low birthweight). Hypoglycaemia can cause brain damage and death, and babies born at risk have an increased risk of developmental delay in later life. Treatment of hypoglycaemia usually involves additional feeding, often with infant formula, and admission to Neonatal Intensive Care for intravenous dextrose. This can be costly and inhibit the establishment of breast feeding. Prevention of neonatal hypoglycaemia would be desirable, but there are currently no strategies, beyond early feeding, for prevention of neonatal hypoglycaemia. Buccal dextrose gel is safe and effective in treatment of hypoglycaemia. The aim of this trial is to determine whether 40% dextrose gel given to babies at risk prevents neonatal hypoglycaemia and hence reduces admission to Neonatal Intensive Care. METHODS/DESIGN: DESIGN: Randomised, multicentre, placebo controlled trial. INCLUSION CRITERIA: Babies at risk of hypoglycaemia (preterm, infant of a diabetic, small or large), less than 1 h old, with no apparent indication for Neonatal Intensive Care Unit admission and mother intends to breastfeed. Trial entry & randomisation: Eligible babies of consenting parents will be allocated by online randomisation to the dextrose gel group or placebo group, using a study number and corresponding trial intervention pack. STUDY GROUPS: Babies will receive a single dose of 0.5 ml/kg study gel at 1 h after birth; either 40% dextrose gel (200 mg/kg) or 2% hydroxymethylcellulose placebo. Gel will be massaged into the buccal mucosal and followed by a breast feed. Primary study outcome: Admission to Neonatal Intensive Care. SAMPLE SIZE: 2,129 babies are required to detect a decrease in admission to Neonatal Intensive Care from 10-6% (two-sided alpha 0.05, 90% power, 5% drop-out rate). DISCUSSION: This study will investigate whether admission to Neonatal Intensive Care can be prevented by prophylactic oral dextrose gel; a simple, cheap and painless intervention that requires no special expertise or equipment and hence is applicable in almost any birth setting. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry--ACTRN 12614001263684. PMID- 26377910 TI - Phosphorylation of the N-methyl-d-aspartate receptor is increased in the nucleus accumbens during both acute and extended morphine withdrawal. AB - Opioid withdrawal causes a dysphoric state that can lead to complications in pain patients and can propagate use in drug abusers and addicts. Opioid withdrawal changes the activity of neurons in the nucleus accumbens, an area rich in both opioid-binding mu opioid receptors and glutamate-binding NMDA receptors. Because the accumbens is an area important for reward and aversion, plastic changes in this area during withdrawal could alter future behaviors in animals. We discovered an increase in phosphorylation of serine 897 in the NR1 subunit of the NMDA receptor (pNR1) during acute morphine withdrawal. This serine can be phosphorylated by protein kinase A (PKA) and dephosphorylated by calcineurin. We next demonstrated that this increased pNR1 change is associated with an increase in NR1 surface expression. NR1 surface expression and pNR1 levels during acute withdrawal were both reduced by the NMDA receptor antagonist MK-801 (dizocilpine hydrogen maleate) and the PKA inhibitor H-89(N-[2-[[3-(4-bromophenyl)-2 propenyl]amino]ethyl]-5-isoquinolinesulfonamide dihydrochloride hydrate). We also found that pNR1 levels remained high after an extended morphine withdrawal period of 2 months, correlated with reward-seeking behavior for palatable food, and were associated with a decrease in accumbal calcineurin levels. These data suggest that NR1 phosphorylation changes during the acute withdrawal phase can be long lasting and may reflect a permanent change in NMDA receptors in the accumbens. These altered NMDA receptors in the accumbens could play a role in long-lasting behaviors associated with reward and opioid use. PMID- 26377911 TI - LG308, a Novel Synthetic Compound with Antimicrotubule Activity in Prostate Cancer Cells, Exerts Effective Antitumor Activity. AB - Microtubule plays many different essential roles in the process of tumorigenesis in many eukaryotes, and targeting mitotic progression by disturbing microtubule dynamics is used as a common strategy for cancer treatment. Microtubule-targeted drugs, including paclitaxel and Vinca alkaloids, were previously considered to work primarily by increasing or decreasing the cellular microtubule mass. The tubulin/microtubule system, which is an integral component of the cytoskeleton, is a therapeutic target for prostate cancer. In this study, we found a novel synthetic compound, 8-fluoro-N-phenylacetyl-1, 3, 4, 9-tetrahydro-beta-carboline (LG308), which disrupted the microtubule organization via inhibiting the polymerization of microtubule in PC-3M and LNCaP prostate cancer cell lines. Further study proved that LG308 induced mitotic phase arrest and inhibited G2/M progression significantly in LNCaP and PC-3M cell lines in a dose-dependent manner, and these were associated with the upregulation of cyclin B1 and mitotic marker MPM-2 and the dephosphorylation of cdc2. Besides, the cell proliferation and colony formation of PC-3M and LNCaP cells were effectively inhibited by LG308. Furthermore, LG308 induced apoptosis and cell death in PC-3M and LNCaP cell lines in vitro. In vivo, LG308 dramatically suppressed the growth and metastasis of prostate cancer in both xenograft and orthotopic models. All these data indicate that LG308 is a promising anticancer candidate with antimitotic activity for the treatment of prostate cancer. PMID- 26377912 TI - SMRT sequencing only de novo assembly of the sugar beet (Beta vulgaris) chloroplast genome. AB - BACKGROUND: Third generation sequencing methods, like SMRT (Single Molecule, Real Time) sequencing developed by Pacific Biosciences, offer much longer read length in comparison to Next Generation Sequencing (NGS) methods. Hence, they are well suited for de novo- or re-sequencing projects. Sequences generated for these purposes will not only contain reads originating from the nuclear genome, but also a significant amount of reads originating from the organelles of the target organism. These reads are usually discarded but they can also be used for an assembly of organellar replicons. The long read length supports resolution of repetitive regions and repeats within the organelles genome which might be problematic when just using short read data. Additionally, SMRT sequencing is less influenced by GC rich areas and by long stretches of the same base. RESULTS: We describe a workflow for a de novo assembly of the sugar beet (Beta vulgaris ssp. vulgaris) chloroplast genome sequence only based on data originating from a SMRT sequencing dataset targeted on its nuclear genome. We show that the data obtained from such an experiment are sufficient to create a high quality assembly with a higher reliability than assemblies derived from e.g. Illumina reads only. The chloroplast genome is especially challenging for de novo assembling as it contains two large inverted repeat (IR) regions. We also describe some limitations that still apply even though long reads are used for the assembly. CONCLUSIONS: SMRT sequencing reads extracted from a dataset created for nuclear genome (re)sequencing can be used to obtain a high quality de novo assembly of the chloroplast of the sequenced organism. Even with a relatively small overall coverage for the nuclear genome it is possible to collect more than enough reads to generate a high quality assembly that outperforms short read based assemblies. However, even with long reads it is not always possible to clarify the order of elements of a chloroplast genome sequence reliantly which we could demonstrate with Fosmid End Sequences (FES) generated with Sanger technology. Nevertheless, this limitation also applies to short read sequencing data but is reached in this case at a much earlier stage during finishing. PMID- 26377913 TI - Opioid rotation versus combination for cancer patients with chronic uncontrolled pain: a randomized study. AB - BACKGROUND: For cancer patients with inadequate pain relief, a switch to an alternative opioid is the preferred option for symptomatic improvement. However, multiple opioids are often simultaneously administered for anecdotal reasons. This prospective study evaluated pain response to either opioid rotation or combination in patients with uncontrolled cancer pain. METHODS: Patients suffering with uncontrolled cancer pain despite dose titration were randomly assigned to opioid rotation group or opioid combination group. Patients answered a questionnaire that included items on pain severity (0 to 10) and interferences at baseline and after one week. RESULTS: Of the 50 patients registered, 39 patients answered the questionnaire after one week of treatment. After one week, the mean pain scores were significantly improved in both groups. Ten patients (42%) in the rotation group and 16 patients (62%) in the combination group reported that they achieved relief from pain (p = 0.08). The incidence of adverse events was similar in both groups, but fewer patients experienced constipation with opioid rotation than with combination (17% vs. 42%, respectively; p = 0.05). The frequency of rescue analgesics (50% vs. 69%; p = 0.17) and dose modification (29% vs. 38%; p = 0.49) were similar in the rotation and combination groups. CONCLUSIONS: For patients with chronic uncontrolled cancer pain, both opioid rotation and combination strategies appear to provide significant relief of pain and improved patient satisfaction. TRIAL REGISTRATION: This study was registered in advance to ClinicalTrials.gov (no. NCT00478101). PMID- 26377914 TI - Changes in transcription of cytokinin metabolism and signalling genes in grape (Vitis vinifera L.) berries are associated with the ripening-related increase in isopentenyladenine. AB - BACKGROUND: Cytokinins are known to play an important role in fruit set and early fruit growth, but their involvement in later stages of fruit development is less well understood. Recent reports of greatly increased cytokinin concentrations in the flesh of ripening kiwifruit (Actinidia deliciosa (A. Chev.) C.F. Liang & A.R. Ferguson) and grapes (Vitis vinifera L.) have suggested that these hormones are implicated in the control of ripening-related processes. RESULTS: A similar pattern of isopentenyladenine (iP) accumulation was observed in the ripening fruit of several grapevine cultivars, strawberry (Fragaria ananassa Duch.) and tomato (Solanum lycopersicum Mill.), suggesting a common, ripening-related role for this cytokinin. Significant differences in maximal iP concentrations between grapevine cultivars and between fruit species might reflect varying degrees of relevance or functional adaptations of this hormone in the ripening process. Grapevine orthologues of five Arabidopsis (Arabidopsis thaliana L.) gene families involved in cytokinin metabolism and signalling were identified and analysed for their expression in developing grape berries and a range of other grapevine tissues. Members of each gene family were characterised by distinct expression profiles during berry development and in different grapevine organs, suggesting a complex regulation of cellular cytokinin activities throughout the plant. The post-veraison-specific expression of a set of biosynthesis, activation, perception and signalling genes together with a lack of expression of degradation related genes during the ripening phase were indicative of a local control of berry iP concentrations leading to the observed accumulation of iP in ripening grapes. CONCLUSIONS: The transcriptional analysis of grapevine genes involved in cytokinin production, degradation and response has provided a possible explanation for the ripening-associated accumulation of iP in grapes and other fruit. The pre- and post-veraison-specific expression of different members from each of five gene families suggests a highly complex and finely-tuned regulation of cytokinin concentrations and response to different cytokinin species at particular stages of fruit development. The same complexity and specialisation is also reflected in the distinct expression profiles of cytokinin-related genes in other grapevine organs. PMID- 26377916 TI - Sugar-containing beverage intake at the age of 1 year and cardiometabolic health at the age of 6 years: the Generation R Study. AB - BACKGROUND: Consumption of sugar-containing beverages (SCBs) in adults has been associated with an increased risk of metabolic syndrome. Although the effect of SCB on body weight in children is well established, little is known about the cardiometabolic effects in young children. We studied the associations of SCB intake at the age of 1 year with cardiometabolic health at age 6 years. METHODS: This study was performed among 2,045 Dutch children from a population based prospective birth cohort. SCB intake was assessed with a semi-quantitative food frequency questionnaire at the age of 13 months and sex-specific tertiles were created. Children visited the research center at the age of 6 years. We created a continuous cardiometabolic risk factor score including: body fat percentage, blood pressure, insulin, HDL-cholesterol and triglycerides. Age-and sex-specific standard deviation (SD) scores were created for all outcomes. Multivariable linear regression was performed with adjustment for socio-demographic and lifestyle variables of mother and child. RESULTS: In the total population, we observed an association between higher SCB intake at 13 months of age and a higher cardiometabolic risk factor score at the age of 6 years (0.13SD (95 % CI 0.01; 0.25), highest vs. lowest tertile) After stratification by sex, we found that boys in the highest tertile of SCB intake had a higher cardiometabolic risk factor score (0.18 SD (95 % CI 0.01; 0.34)), as compared to boys in the lowest tertile of SCB intake. There was no significant association in girls. We did not find associations of SCB intake with the individual cardiometabolic risk factors in the total population, or in the stratified analyses. CONCLUSION: Higher SCB intake at 1 year of age was associated with a higher cardiometabolic risk factor score at age 6 years in boys, but not in girls. Further research on sex-specific effects of SCBs is needed. PMID- 26377915 TI - Interleukin-36gamma is expressed by neutrophils and can activate microglia, but has no role in experimental autoimmune encephalomyelitis. AB - BACKGROUND: Experimental autoimmune encephalomyelitis (EAE) is a model of inflammatory demyelinating diseases mediated by different types of leukocytes. How these cells communicate with each other to orchestrate autoimmune attacks is not fully understood, especially in the case of neutrophils, whose importance in EAE is newly established. The present study aimed to determine the expression pattern and role of different components of the IL-36 signaling pathway (IL 36alpha, IL-36beta, IL-36gamma, IL-36R) in EAE. METHODS: EAE was induced by either active immunization with myelin peptide, passive transfer of myelin reactive T cells or injection of pertussis toxin to transgenic 2D2 mice. The molecules of interest were analyzed using a combination of techniques, including quantitative real-time PCR (qRT-PCR), flow cytometry, Western blotting, in situ hybridization, and immunohistochemistry. Microglial cultures were treated with recombinant IL-36gamma and analyzed using DNA microarrays. Different mouse strains were subjected to clinical evaluation and flow cytometric analysis in order to compare their susceptibility to EAE. RESULTS: Our observations indicate that both IL-36gamma and IL-36R are strongly upregulated in nervous and hematopoietic tissues in different forms of EAE. IL-36gamma is specifically expressed by neutrophils, while IL-36R is expressed by different immune cells, including microglia and other myeloid cells. In culture, microglia respond to recombinant IL-36gamma by expressing molecules involved in neutrophil recruitment, such as Csf3, IL-1beta, and Cxcl2. However, mice deficient in either IL-36gamma or IL-36R develop similar clinical and histopathological signs of EAE compared to wild-type controls. CONCLUSION: This study identifies IL-36gamma as a neutrophil-related cytokine that can potentially activate microglia, but that is only correlative and not contributory in EAE. PMID- 26377917 TI - Placental mitochondrial DNA content and placental abruption: a pilot study. AB - BACKGROUND: Mitochondrial biogenesis and adequate energy production are important for embryogenesis and placentation. Previous studies documented alterations in maternal blood mitochondrial DNA (mtDNA) copy number-a marker of mitochondrial dysfunction-in pregnancies complicated by placental abruption. To further understand the role of mitochondrial dysfunction in the pathogenesis of placental abruption, we conducted a pilot study using placental specimen collected from 103 placental abruption cases and 102 non-abruption controls. Real-time quantitative polymerase chain reaction (PCR) was used to assess the relative copy number of mtDNA in DNA extracted from placental samples collected immediately after delivery. Logistic regression procedures were used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Higher odds of placental abruption was observed with increasing mtDNA copy number (p value for trend = 0.05). The odds of placental abruption was elevated among women who delivered placentas with higher mtDNA copy number (>=120.5, the median) as compared with those with lower values (<120.5) (adjusted OR = 2.38; 95% CI 1.11-5.08). CONCLUSION: We found preliminary evidence for associations of target tissue specific mitochondrial dysfunction with an adverse perinatal outcome, placental abruption. Larger studies and replication of findings in other populations will further our understanding of relationships between cellular and genomic biomarkers of normal and abnormal placental function and vascular placental disorders. PMID- 26377918 TI - Prevalence and risk factors of gammaherpesvirus infection in domestic cats in Central Europe. AB - BACKGROUND: Gammaherpesviruses (GHVs) are a large group of dsDNA viruses that can infect humans and several animal species. The two human GHVs, Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus are known for their oncogenic properties in individuals with immunodeficiency. Recently, the first feline GHV, Felis catus gammaherpesvirus 1 (FcaGHV1) was discovered and frequently found in domestic cats in Australia, Singapore and the USA. FcaGHV1 is more likely to be detected in cats co-infected with the feline immunodeficiency virus (FIV). FINDINGS: The prevalence of FcaGHV1 in pet cats from Germany and Austria was 16.2 % (95 % CI = 12.38-20.02). The odds for GHV infection were greater for FIV positive (OR = 4.5), male (OR = 13.32) and older (OR = 2.36) cats. Furthermore, FcaGHV1 viral loads were significantly higher in FIV-infected cats compared to matched controls. CONCLUSIONS: GHV infections are common in domestic cats in Central Europe. The worldwide distribution of FcaGHV1 can be assumed. A potential role as a co-factor in FIV-induced pathogeneses is supported. PMID- 26377919 TI - The role of peer physical activity champions in the workplace: a qualitative study. AB - AIMS: Peer health champions have been suggested as an important component of multilevel workplace interventions to promote healthy behaviours such as physical activity (PA). There is accumulating quantitative evidence of their effectiveness but as yet little exploration of why and how champions influence peer behaviour. The current study explores the role of peer physical activity champions (PPACs) in influencing colleagues' PA behaviour from the perspectives of both champions and colleagues. METHODS: Seven months after the introduction of a workplace PA programme in 17 small- and medium-sized enterprises (SMEs), two focus groups were held with PPACs and four with programme participants. Data were analysed using inductive thematic analysis. RESULTS: Three overarching themes were developed: how PPACs encourage PA, valuable PPAC characteristics and sustaining motivation for the PPAC role. Both direct encouragement from PPACs and facilitation of wider PA supportive social networks within the workplace encouraged behaviour change. PA behaviour change is a delicate subject and it was important that PPACs provided enthusiastic and persistent encouragement without seeming judgemental. Being a PA role model was also a valuable characteristic. The PPACs found it satisfying to see positive changes in their colleagues who had become more active. However, colleagues often did not engage in suggested activities and PPACs required resilience to maintain personal motivation for the role despite this. CONCLUSION: Incorporating PPACs into SME-based PA interventions is acceptable to employees. It is recommended that PPAC training includes suggestions for facilitating social connections between colleagues. Sensitivity is required when initiating and engaging in conversations with colleagues about increasing their PA. Programmes should ensure PPACs themselves are provided with social support, especially from others in the same role, to help sustain motivation for their role. These findings will be useful to health-promotion professionals developing workplace health programmes. PMID- 26377920 TI - [Periradicular infiltration therapy : Clinical indications, technique and results]. AB - BACKGROUND: Minimally invasive procedures have played an emerging role in pain management during recent years. OBJECTIVES: Evaluation of the different types of periradicular infiltration as fundamental procedures in the progressive stepwise concept of pain management. Comparison of the different therapeutic substances. RESULTS: In the mid-term and long-term periradicular infiltration is effective in 60-80 % of patients regarding analgesic and functional aspects. Compliance with the guidelines should help to minimize potentially fatal complications. CONCLUSION: Periradicular infiltration is of significant importance concerning the treatment of spinal nerve root irritation. Periradicular infiltration is regarded as a safe procedure, especially when supported by computed tomography (CT) scans. PMID- 26377921 TI - Mucinous tubular and spindle cell renal cell carcinoma: a review of clinicopathologic aspects. AB - Mucinous tubular and spindle cell renal cell carcinoma is a rare, recently described variant of renal cell carcinoma characterized by an admixture of cuboidal cells in tubules and sheets of spindle cells, and variable amounts of mucinous stroma. It has been recognized as a distinct entity in the 2004 World Health Organization tumor classification. Since then, several dozen of these tumor have been reported with additional complementary morphologic characteristics, immunohistochemical profile, and molecular genetic features that have further clarified its clinicopathologic aspects. Although originally considered as a low grade renal cell carcinoma on the basis of its bland appearing nuclear features and indolent clinical course, mucinous tubular and spindle cell renal cell carcinoma has currently been proven to be a tumor that has a histological spectrum ranging from low to high grade that includes sarcomatoid differentiation. In this review, we present a detailed summary of the current knowledge regarding the clinicopathologic, immunohistochemical, molecular genetic, and prognostic characteristics, as well as differential diagnoses of mucinous tubular and spindle cell renal cell carcinoma. PMID- 26377922 TI - Microbial enhanced heavy crude oil recovery through biodegradation using bacterial isolates from an Omani oil field. AB - BACKGROUND: Biodegradation is a cheap and environmentally friendly process that could breakdown and utilizes heavy crude oil (HCO) resources. Numerous bacteria are able to grow using hydrocarbons as a carbon source; however, bacteria that are able to grow using HCO hydrocarbons are limited. In this study, HCO degrading bacteria were isolated from an Omani heavy crude oil field. They were then identified and assessed for their biodegradation and biotransformation abilities under aerobic and anaerobic conditions. RESULTS: Bacteria were grown in five different minimum salts media. The isolates were identified by MALDI biotyper and 16S rRNA sequencing. The nucleotide sequences were submitted to GenBank (NCBI) database. The bacteria were identified as Bacillus subtilis and B. licheniformis. To assess microbial growth and biodegradation of HCO by well-assay on agar plates, samples were collected at different intervals. The HCO biodegradation and biotransformation were determined using GC-FID, which showed direct correlation of microbial growth with an increased biotransformation of light hydrocarbons (C12 and C14). Among the isolates, B. licheniformis AS5 was the most efficient isolate in biodegradation and biotransformation of the HCO. Therefore, isolate AS5 was used for heavy crude oil recovery experiments, in core flooding experiments using Berea core plugs, where an additional 16 % of oil initially in place was recovered. CONCLUSIONS: This is the first report from Oman for bacteria isolated from an oil field that were able to degrade and transform HCO to lighter components, illustrating the potential use in HCO recovery. The data suggested that biodegradation and biotransformation processes may lead to additional oil recovery from heavy oil fields, if bacteria are grown in suitable medium under optimum growth conditions. PMID- 26377925 TI - Fighting the Derpy Science of Sexuality. PMID- 26377923 TI - Metabolic modeling predicts metabolite changes in Mycobacterium tuberculosis. AB - BACKGROUND: Mycobacterium tuberculosis (MTB) is the causal agent of the disease tuberculosis (TB). Metabolic adaptations are thought to be critical to the survival of MTB during pathogenesis. Computational tools that can be used to study MTB metabolism in silico and prioritize resource-intensive experimental work could significantly accelerate research. RESULTS: We have developed E-Flux MFC, an enhancement of our original E-Flux method that enables the prediction of changes in the production of external and internal metabolites corresponding to gene expression measurements. We have used this method to simulate the changes in the metabolic state of Mycobacterium tuberculosis (MTB). We have validated the accuracy of E-Flux-MFC for predicting changes in lipids and metabolites during a hypoxia time course using previously published metabolomics and transcriptomics data. We have further validated the accuracy of the method for predicting changes in MTB lipids following the deletion and induction of two well-studied transcription factors (TFs). We have applied the method to predict the metabolic impact of the induction of each of the approximately 180 MTB TFs using a previously generated and publically available expression data set. CONCLUSIONS: E flux-MFC can be used to study global changes in MTB metabolites from gene expression data associated with environmental and genetic perturbations. The application of this method to a data set of MTB TF perturbations provides a resource for studying the large number of TFs whose functions remain unknown. Most TFs impact metabolites indirectly through the propagation of gene expression changes through the regulatory network rather than through their direct regulons. E-Flux-MFC is also applicable to any organism for which accurate metabolic models are available. PMID- 26377924 TI - Normal tissue complication probability modeling for cochlea constraints to avoid causing tinnitus after head-and-neck intensity-modulated radiation therapy. AB - BACKGROUND: Radiation-induced tinnitus is a side effect of radiotherapy in the inner ear for cancers of the head and neck. Effective dose constraints for protecting the cochlea are under-reported. The aim of this study is to determine the cochlea dose limitation to avoid causing tinnitus after head-and-neck cancer (HNC) intensity-modulated radiation therapy (IMRT). METHODS: In total 211 patients with HNC were included; the side effects of radiotherapy were investigated for 422 inner ears in the cohort. Forty-nine of the four hundred and twenty-two samples (11.6%) developed grade 2+ tinnitus symptoms after IMRT, as diagnosed by a clinician. The Late Effects of Normal Tissues-Subjective, Objective, Management, Analytic (LENT-SOMA) criteria were used for tinnitus evaluation. The logistic and Lyman-Kutcher-Burman (LKB) normal tissue complication probability (NTCP) models were used for the analyses. RESULTS: The NTCP-fitted parameters were TD 50 = 46.31 Gy (95% CI, 41.46-52.50), gamma 50 = 1.27 (95% CI, 1.02-1.55), and TD 50 = 46.52 Gy (95% CI, 41.91-53.43), m = 0.35 (95% CI, 0.30-0.42) for the logistic and LKB models, respectively. The suggested guideline TD 20 for the tolerance dose to produce a 20% complication rate within a specific period of time was TD 20 = 33.62 Gy (95% CI, 30.15-38.27) (logistic) and TD 20 = 32.82 Gy (95% CI, 29.58-37.69) (LKB). CONCLUSIONS: To maintain the incidence of grade 2+ tinnitus toxicity <20% in IMRT, we suggest that the mean dose to the cochlea should be <32 Gy. However, models should not be extrapolated to other patient populations without further verification and should first be confirmed before clinical implementation. PMID- 26377926 TI - Flibanserin. PMID- 26377927 TI - Chemopreventive Properties of Genipin on AGS Cell Line via Induction of JNK/Nrf2/ARE Signaling Pathway. AB - Roles of dietary phytochemicals in cancer chemoprevention via induction of nuclear factor-erythroid-2-related factor 2 (Nrf2)-mediated antioxidant enzymes have been well established in a number of studies. In this study, FACS analysis was used to reveal that the intracellular reactive oxygen species level decreased at 0-25 MUM of genipin treatment. Furthermore, immunofluorescence analysis and Western blotting were used to demonstrate that genipin treatment resulted in the upregulation and nuclear translocation of Nrf2, as well as upregulation of gastrointestinal glutathione peroxidase. Finally, we found that C-Jun-NH2-kinase (JNK) was also dose-dependently activated, where depleting JNK by using a biochemical inhibitor indicated that JNK was upstream of Nrf2. Interestingly, the antioxidant effects were limited to the treatment in the lower dosage of genipin, where higher dosage of genipin treatment resulted in the increased reactive oxygen species level and cytotoxicity. Thus, this study demonstrates for the first time that lower dosage of genipin results in the induction of JNK/Nrf2/ARE signaling pathway and protection from cell death. PMID- 26377928 TI - Anthropometric approach to lumbar vertebral body volumes. AB - OBJECTIVE: To assess the relationship between the maximum volume of lumbar vertebral bodies and patient morphological features. Knowledge of the volume of the vertebral body is useful when performing vertebroplasty and kyphoplasty. METHODS: 129 patients (18-85 years) were included consecutively over an 8-month period. All had been subject to abdominopelvic CT scans. The weight, height and body mass index (BMI) were known. The volume of each vertebral body was calculated using the formula V = pi R (2). H (V = volume, R = radius, H = height). A statistical analysis of the data divided into three groups, men/women, men only and women only, was conducted by calculating the Pearson correlation coefficient. RESULTS: The volume of the vertebral body increased from L1 to L4, but the volume of the L5 vertebral body was lower than that of L3 and L4 in all three groups. The volumes of the vertebral bodies were greater in men than in women. Calculating the correlation coefficient showed that the variable most correlated with volume was patient's height in both the men/women and women-only groups, while the most correlated variable in the male-only group was weight. Vertebral height was the variable most correlated with overall height in all three groups. CONCLUSION: There is a wide variability in the volume of lumbar vertebrae. The volume of the vertebral body appears to vary not only with a person's height but also their weight. The vertebral body seems to expand with weight in men. PMID- 26377929 TI - Robotic spleen-preserving laparoscopic distal pancreatectomy: a single-centered Chinese experience. AB - BACKGROUND: Spleen-preserving laparoscopic distal pancreatectomy is technically challenging. New surgical robotic systems are now available and show promising outcomes but were very recently implemented in China. METHODS: Seven patients underwent laparoscopic distal pancreatectomy using the da Vinci Robotic System (RDP) for benign or borderline malignant pancreatic tumors. Spleen preservation rate, blood loss, and operative complications were assessed. RESULTS: Mean age was 44.6 +/- 13.7 years. Surgery was uneventful in all patients, without conversion to laparotomy. The surgical time (including anesthesia induction, robot docking, operation, and postoperative awaking time) was 460 +/- 154 min, while the operation time was 368 +/- 126 min. Blood losses were 200 +/- 110 mL. The minor (Clavien I+II) complication rate was 14.3%, and the major (Clavien III+IV) complication rate was 14.3 %, including hemorrhage and pancreatic leakage. The spleen preservation rate was 100%. All complications were successfully managed and cured. Intraoperative laparoscopic ultrasound examination successfully identified the correct surgical resection margins. Mean postoperative hospitalization was 8.7 +/- 6.6 days. No patient had to undergo a second pancreas surgery. Patients were followed up for a median of 6.8 months (range, 6 to 22 months). All patients survived and reported few discomforts. CONCLUSIONS: RDP is feasible and allows the preservation of the splenic vessels. PMID- 26377930 TI - A new class of insecticide for malaria vector control: evaluation of mosquito nets treated singly with indoxacarb (oxadiazine) or with a pyrethroid mixture against Anopheles gambiae and Culex quinquefasciatus. AB - BACKGROUND: Universal coverage with long-lasting insecticidal mosquito nets (LLIN) or indoor residual spraying (IRS) of houses remain the primary strategies for the control of mosquito vectors of malaria. Pyrethroid resistant malaria vectors are widespread throughout sub-Saharan Africa and new insecticides with different modes of action are urgently needed if malaria vector control is to remain effective. Indoxacarb is an oxadiazine insecticide that is effective as an oral and contact insecticide against a broad spectrum of agricultural pests and, due to its unique site of action, no cross-resistance has been detected through mechanisms associated with resistance to insecticides currently used in public health. METHODS: WHO tunnel tests of host seeking mosquitoes were carried out as a forerunner to experimental hut trials, to provide information on dosage dependent mortality, repellency, and blood-feeding inhibition. A dosage range of indoxacarb treated netting (100-1000 mg/m(2)) was tested against a pyrethroid susceptible strain of Anopheles gambiae. In addition, efficacy of indoxacarb 500 mg/m(2) was compared with a standard pyrethroid formulation against pyrethroid susceptible and resistant Culex quinquefasciatus. Dosages between 25 and 300 mg/m(2) indoxacarb were tested in tunnel tests and in ball-frame bioassays as mixtures with alphacypermethrin 25 mg/m(2) and were compared with singly applied treatments against an insectary reared pyrethroid resistant strain of Cx. quinquefasciatus originally collected in Cotonou, Benin. RESULTS: There was a dosage-dependent response in terms of indoxacarb induced mortality, with dosages >100 mg/m(2) producing the best mortality response. In tunnel tests indoxacarb 500 mg/m(2) exceeded WHOPES thresholds with >80 % mortality of adult An. gambiae and blood-feeding inhibition of 75 %. No cross-resistance to indoxacarb was detected through mechanisms associated with resistance to pyrethroid insecticides and was equally effective against susceptible and resistant strains of Cx. quinquefasciatus. Indoxacarb 500 mg/m(2) killed 75 % of pyrethroid resistant Cx. quinquefasciatus compared with only 21 % mortality with alphacypermethrin 40 mg/m(2). Mixtures of indoxacarb with pyrethroid produced an additive response for both mortality and blood-feeding inhibition. The best performing mixture (indoxacarb 200 mg/m(2) + alphacypermethrin 25 mg/m(2)) killed 83 % of pyrethroid resistant Cx. quinquefasciatus and reduced blood-feeding by 88 %, while alphacypermethrin only killed 36 % and inhibited blood-feeding by 50 %. CONCLUSIONS: New insecticides with different modes of action to those currently used in mosquito vector control are urgently needed. Indoxacarb shows great promise as a mixture with a pyrethroid and should be evaluated in experimental hut trials to determine performance against wild free-flying, pyrethroid resistant An. gambiae and wash-resistant formulations developed. PMID- 26377931 TI - Aromatic Esters of Bicyclic Amines as Antimicrobials against Streptococcus pneumoniae. AB - A double approach was followed in the search of novel inhibitors of the surface choline-binding proteins (CBPs) of Streptococcus pneumoniae (pneumococcus) with antimicrobial properties. First, a library of 49 rationally-designed esters of alkyl amines was screened for their specific binding to CBPs. The best binders, being esters of bicyclic amines (EBAs), were then tested for their in vitro effect on pneumococcal growth and morphology. Second, the efficiency of EBA induced CBP inhibition was enhanced about 45,000-fold by multivalency effects upon synthesizing a poly(propylene imine) dendrimer containing eight copies of an atropine derivative. Both approaches led to compounds that arrest bacterial growth, dramatically decrease cell viability, and exhibit a protection effect in animal disease models, demonstrating that the pneumococcal CBPs are adequate targets for the discovery of novel antimicrobials that overcome the currently increasing antimicrobial resistance issues. PMID- 26377932 TI - Responsiveness of the autonomic nervous system during paced breathing and mental stress in migraine patients. AB - BACKGROUND: Migraine is a stress-related disorder, suggesting that there may be sympathetic hyperactivity in migraine patients. However, there are contradictory results concerning general sympathetic activation in migraine patients. To shed more light on the involvement of the autonomic nervous system (ANS) in migraine pathophysiology, we investigated cardiac and cardiovascular reactions during vagal (paced breathing) and sympathetic activation (mental stress test). METHODS: Heart rate variability parameters and skin conductance responses were recorded interictally in 22 episodic migraine patients without aura and 25 matched controls during two different test conditions. The paced breathing test consisted of a five-minute baseline, followed by two minutes of paced breathing (6 breathing cycles per minute) and a five-minute recovery phase. The mental stress test consisted of a five-minute baseline, followed by one minute of stress anticipation, three and a half minutes of mental stress and a five-minute recovery phase. Furthermore we measured blood pressure and heart rate once daily over 2 weeks. Subjects rated their individual current stress level and their stress level during paced breathing and during the mental stress test. RESULTS: There were no significant differences between migraine patients and controls in any of the heart rate variability parameters in either time domain or frequency domain analysis. However, all parameters showed a non-significant tendency for larger sympathetic activation in migraine patients. Also, no significant differences could be observed in skin conductance responses and average blood pressure. Only heart rates during the 2-week period and stress ratings showed significantly higher values in migraine patients compared to controls. CONCLUSIONS: Generally there were no significant differences between migraine patients and controls concerning the measured autonomic parameters. There was a slight but not significant tendency in the migraine patients to react with less vagal and more sympathetic activation in all these tests, indicating a slightly changed set point of the autonomic system. Heart rate variability and blood pressure in migraine patients should be investigated for longer periods and during more demanding sympathetic activation. PMID- 26377933 TI - A forensic hypothesis for the mystery of al-Hasan's death in the 7th century: Mercury(I) chloride intoxication. AB - The puzzle of a mysterious death in the Middle Ages has been hypothesized in terms of contemporary forensic legal and scientific methods. That al-Hasan ibn 'Ali died in 669 aged just 45 has been forensically analyzed based on written sources that dictate eyewitness accounts of historical events. The report of the contemporaneous poisoning of another individual who resided under the same household as al-Hasan's and experienced similar, yet non-lethal, symptoms has served as the beginning of the analysis. In light of ancient (medieval) documents and through using mineralogical, medical, and chemical facts, it has been hypothesized that mineral calomel (mercury(I) chloride, Hg2Cl2) from a certain region in the Byzantine Empire (present-day western Turkey) was the substance primarily responsible for the murder of al-Hasan. PMID- 26377934 TI - An incest case with three biological brothers as alleged fathers: Even 22 autosomal STR loci analysis would not suffice without the mother. AB - Here, we report an incest paternity case involving three biological brothers as alleged fathers (AFs), their biological sister and her child that was investigated using the Investigator ESSplex Plus, AmpFLSTR Identifiler Plus/Investigator IDplex Plus and PowerPlex 16 kits. Initial duo paternity investigations using 15-loci autosomal short tandem repeat (STR) analyses failed to exclude any of the AFs. Despite the fact that one of the brothers, AF1, had a mismatch with the child at a single locus (D2S1338), the possibility of a single step mutation could not be ruled out. When the number of autosomal STR loci analysed was increased to 22 without the inclusion of the mother, AF2 and AF3 still could not be excluded, since both of them again had no mismatches with the child. A breakthrough was possible only upon inclusion of the mother so that trio paternity investigations were carried out. This time AF1 and AF2 could be excluded at two loci (D2S1338 and D1S1656) and six loci (vWa, D1S1656, D12S391, FGA, PENTA E and PENTA D), respectively, and AF3 was then the only brother who could not be excluded from paternity. Subsequent statistical analyses suggested that AF3 could be the biological father of the child with a combined paternity index >100 billion and a probability of paternity >99.99999999%. These findings consolidate the fact that complex paternity cases such as those involving incest could benefit more from the inclusion of the mother than simply increasing the number of STR loci analysed. PMID- 26377935 TI - Maintenance therapy for colorectal cancer: which regimen and which patients? AB - The introduction of therapeutic agents such as irinotecan, oxaliplatin, and more recently biologic agents such as vascular endothelial growth factor and epidermal growth factor receptor (EGFR) inhibitors has significantly improved survival of patients with metastatic colorectal cancer. These novel agents have also contributed to added toxicities. Therefore, several studies have evaluated the role of maintenance therapy with less intensive regimens in patients who experienced stable disease or treatment response following induction therapy as a strategy to reduce toxicity and improve quality of life. The success of such strategies, however, requires assurance that their survival would not be compromised. We therefore reviewed studies that have explored the various strategies of treatment de-escalation with an emphasis on survival and toxicity outcomes. Recent studies evaluated the role of maintenance therapy with chemotherapy only, chemotherapy plus bevcizumab, bevacizumab only, and EGFR inhibitors. Current evidence suggests that maintenance strategies offer significant benefit to patients by providing continuous clinical benefit while minimizing the risks associated with continuous therapy. Strategies to improve selection of patients for maintenance therapy versus identifying subgroups of patients that will benefit from a chemotherapy-free interval need to continue to be studied. Finally, as our understanding of the molecular and genetic drivers of colorectal cancer continues to expand, refining these strategies to include more target-specific agents should become more routine. PMID- 26377936 TI - An infrared spectroscopy method to detect ammonia in gastric juice. AB - Ammonia in gastric juice is considered a potential biomarker for Helicobacter pylori infection and as a factor contributing to gastric mucosal injury. High ammonia concentrations are also found in patients with chronic renal failure, peptic ulcer disease, and chronic gastritis. Rapid and specific methods for ammonia detection are urgently required by the medical community. Here we present a method to detect ammonia directly in gastric juice based on Fourier transform infrared spectroscopy. The ammonia dissolved in biological liquid samples as ammonium ion was released in air as a gas by the shifting of the pH equilibrium of the ammonium/ammonia reaction and was detected in line by a Fourier transform infrared spectroscopy system equipped with a gas cell for the quantification. The method developed provided high sensitivity and selectivity in ammonia detection both in pure standard solutions and in a simulated gastric juice matrix over the range of diagnostic concentrations tested. Preliminary analyses were also performed on real gastric juice samples from patients with gastric mucosal injury and with symptoms of H. pylori infection, and the results were in agreement with the clinicopathology information. The whole analysis, performed in less than 10 min, can be directly applied on the sample without extraction procedures and it ensures high specificity of detection because of the ammonia fingerprint absorption bands in the infrared spectrum. This method could be easily used with endoscopy instrumentation to provide information in real time and would enable the endoscopist to improve and integrate gastroscopic examinations. PMID- 26377937 TI - Quantification of sphingosine 1-phosphate by validated LC-MS/MS method revealing strong correlation with apolipoprotein M in plasma but not in serum due to platelet activation during blood coagulation. AB - Sphingosine 1-phosphate (S1P) is a signalling sphingolipid affecting multiple cellular functions of vascular and immune systems. It circulates at submicromolar levels bound to HDL-associated apolipoprotein M (apoM) or to albumin. S1P in blood is mainly produced by platelets and erythrocytes, making blood sampling for S1P quantification delicate. Standardisation of sampling is thereby of great importance to obtain robust data. By optimising and characterising the extraction procedure and the LC-MS/MS analysis, we have developed and validated a highly specific and sensitive method for S1P quantification. Blood was collected from healthy individuals (n = 15) to evaluate the effects of differential blood sampling on S1P levels. To evaluate correlation between S1P and apoM in different types of plasma and serum, apoM was measured by ELISA. The method showed good accuracy and precision in the range of 0.011 to 0.9 MUM with less than 0.07 % carryover. We found that the methanol precipitation used to extract S1P co extracted apoM and several other HDL-proteins from plasma. The platelet associated S1P was released during coagulation, thus increasing the S1P concentration to double in serum as compared to that in plasma. Gel filtration chromatography revealed that the platelet-released S1P was mainly bound to albumin. This explains why the strong correlation between S1P and apoM levels in plasma is lost upon the clotting process and hence not observed in serum. We have developed, characterised and validated an efficient, highly sensitive and specific method for the quantification of S1P in biological material. PMID- 26377938 TI - Nutritional evaluation of phosphorylated pumpkin seed (Cucurbita moschata) protein concentrate in silver catfish Rhamdia quelen (Quoy and Gaimard, 1824). AB - An 8-week feeding trial was conducted to evaluate the effect of replacing fish meal with pumpkin seed meal (PSM) or phosphorylated protein concentrate of pumpkin seed meal (PPCPS) on growth and metabolic responses of silver catfish. Five isonitrogenous and isocaloric diets were formulated. Control diet contained fish meal as the main protein source. The treatment groups contained 25 and 50% of either PSM or PPCPS protein replaced the fishmeal protein. A total of 400 silver catfish, with initial mean weight of 24 +/- 0.46 g, were distributed into 20 tanks. For data four orthogonal contrasts were applied: control diet versus PSM diets; control diets versus PPCPS diets; control versus other diets; PSM diets versus PPCPS diets. The results indicated that the fish fed PSM diets had lower weight gain when compared to either control diet or PPCPS. The PPCPS do not affect growth and protein efficiency ratio. Lower albumin contents were found for the control diet fish for the contrasts control diet versus PPCPS diet and control diet versus other diets. The hepatic ALAT enzyme activity was higher in the fish fed the control diet (P < 0.05). The hepatic ALP was most active in fish that received the PPCPS diets, when comparing control diet versus PPCPS diets and control diet versus other diets. The hepatosomatic index was higher for fish fed the PPCPS. Our results indicated that PPCPS presents relevant nutritional quality for fish and can replace the fish meal protein up to 50% without affecting growth, PER and intermediate metabolites in silver catfish. PMID- 26377939 TI - Characterization and genomic structure of Dnah9, and its roles in nodal signaling pathways in the Japanese flounder (Paralichthys olivaceus). AB - The nodal signaling pathway has been shown to play crucial roles in inducing and patterning the mesoderm and endoderm, as well as in regulating neurogenesis and left-right axis asymmetry. Here, we present the first complete cDNA and genomic sequences as well as the promoter predication of the Dnah9 gene in the Japanese flounder. The 15,558-bp-long cDNA is divided into 96 exons and spread over 138 kb of genomic DNA. Protein sequence comparison showed that it shares higher identity with other vertebrate orthologs, with an ATP binding dynein motor, AAA domain and microtubule binding stalk of dynein motor. Dnah9 exhibited maternal and ubiquitous expression in all cells of the early development stages, but became concentrated in the head at 1 DAH, as identified by qRT-PCR and in situ hybridization methods. Furthermore, after nodal signaling was inhibited, the level of Southpaw did not change significantly at early development stage (50 % epiboly) but increased significantly at late stages (27-somite stages and 1 DAH), as well as the expression of Lefty, an inhibitor of nodal signaling, increased continuously. On the other hand, the expression level of Dnah9 decreased. The transcription factor binding site of FAST-1 (SMAD interacting protein) was identified in the transcription region of Dnah9 by the promoter analysis, which might format the complexes of SMADs, FAST-1 and the transcription region of Dnah9 served as a bridge of Dnah9 and nodal signaling. All evidences indicated that Dnah9 might be downstream of nodal during the early development stages, and an indirect function through SMADs for nodal signaling pathway. PMID- 26377940 TI - Dll4 Blockade in Stromal Cells Mediates Antitumor Effects in Preclinical Models of Ovarian Cancer. AB - The Notch ligand delta-like 4 (Dll4) has been identified as a promising target in tumor angiogenesis in preclinical studies, and Dll4 inhibitors have recently entered clinical trials for solid tumors, including ovarian cancers. In this study, we report the development of REGN421 (enoticumab), a fully human IgG1 monoclonal antibody that binds human Dll4 with sub-nanomolar affinity and inhibits Notch signaling. Administering REGN421 to immunodeficient mice engineered to express human Dll4 inhibited the growth of several human tumor xenografts in association with the formation of nonfunctional tumor blood vessels. In ovarian tumor xenograft models, Dll4 was expressed specifically by the tumor endothelium, and Dll4 blockade by human-specific or mouse-specific Dll4 antibodies exerted potent antitumor activity, which relied entirely on targeting Dll4 expressed by tumor stromal cells but not by the tumor cells themselves. However, Dll4 blockade reduced Notch signaling in both blood vessels and tumor cells surrounding the blood vessels, suggesting that endothelial-expressed Dll4 might induce Notch signaling in adjacent ovarian tumor cells. The antitumor effects of targeting Dll4 were augmented significantly by simultaneous inhibition of VEGF signaling, whereas this combined blockade reversed normal organ vascular changes induced by Dll4 blockade alone. Overall, our findings deepen the rationale for antibody-based strategies to target Dll4 in ovarian cancers, especially in combination with VEGF blockade. PMID- 26377941 TI - The Stress Kinase p38alpha as a Target for Cancer Therapy. AB - p38alpha is a ubiquitous protein kinase strongly activated by stress signals, inflammatory cytokines, and many other stimuli, which has been implicated in the modulation of multiple cellular processes. There is good evidence in the literature that p38alpha plays an important tumor-suppressor role by interfering with malignant cell transformation. This is mainly based on the ability of the p38alpha pathway to regulate tissue homeostasis by integrating signals that balance cell proliferation and differentiation or induce apoptosis. However, recent reports have also illustrated protumorigenic functions for p38alpha. Thus, p38alpha signaling may facilitate the survival and proliferation of tumor cells contributing to the progression of some tumor types. In addition, p38alpha activation helps tumor cells to survive chemotherapeutic treatments. In all these cases, the inhibition of p38alpha has a potential therapeutic interest. Further elucidation of the context-dependent functions of p38alpha signaling in tumoral processes is of obvious importance for the use of inhibitors of this pathway in cancer therapy. PMID- 26377942 TI - Comparative transcriptome analyses of deltamethrin-susceptible and -resistant Culex pipiens pallens by RNA-seq. AB - The widespread and improper use of pyrethroid insecticides, such as deltamethrin, has resulted in the evolution of resistance in many mosquito species, including Culex pipiens pallens. With the development of high-throughput sequencing, it is possible to massively screen pyrethroid resistance-associated gene. In this study, we used Illumina-Solexa transcriptome sequencing to identify genes that are expressed differently in deltamethrin-susceptible and -resistant strains of Culex pipiens pallens as a critical knowledge base for further studies. A total of 4,961,197,620 base pairs and 55,124,418 reads were sequenced, mapped to the Culex quinquefasciatus genome and assembled into 17,679 known genes. We recorded 1826 significantly differentially expressed genes (DEGs). Among them, 1078 genes were up-regulated and 748 genes were down-regulated in the deltamethrin-resistant strain compared to -susceptible strain. These DEGs contained cytochrome P450 s, cuticle proteins, UDP-glucuronosyltransferases, lipases, serine proteases, heat shock proteins, esterases and others. Among the 1826 DEGs, we found that the transcriptional levels of CYP6AA9 in the laboratory populations was elevated as the levels of deltamethrin resistance increased. Moreover, the expression levels of the CYP6AA9 were significantly higher in the resistant strains than the susceptible strains in three different field populations. We further confirmed the association between the CYP6AA9 gene and deltamethrin resistance in mosquitoes by RNA interfering (RNAi). Altogether, we explored massive potential pyrethroid resistance-associated genes and demonstrated that CYP6AA9 participated in the pyrethroid resistance in mosquitoes. PMID- 26377943 TI - Characterization of the temperate phage vB_RleM_PPF1 and its site-specific integration into the Rhizobium leguminosarum F1 genome. AB - Bacteriophages may play an important role in regulating population size and diversity of the root nodule symbiont Rhizobium leguminosarum, as well as participating in horizontal gene transfer. Although phages that infect this species have been isolated in the past, our knowledge of their molecular biology, and especially of genome composition, is extremely limited, and this lack of information impacts on the ability to assess phage population dynamics and limits potential agricultural applications of rhizobiophages. To help address this deficit in available sequence and biological information, the complete genome sequence of the Myoviridae temperate phage PPF1 that infects R. leguminosarum biovar viciae strain F1 was determined. The genome is 54,506 bp in length with an average G+C content of 61.9 %. The genome contains 94 putative open reading frames (ORFs) and 74.5 % of these predicted ORFs share homology at the protein level with previously reported sequences in the database. However, putative functions could only be assigned to 25.5 % (24 ORFs) of the predicted genes. PPF1 was capable of efficiently lysogenizing its rhizobial host R. leguminosarum F1. The site-specific recombination system of the phage targets an integration site that lies within a putative tRNA-Pro (CGG) gene in R. leguminosarum F1. Upon integration, the phage is capable of restoring the disrupted tRNA gene, owing to the 50 bp homologous sequence (att core region) it shares with its rhizobial host genome. Phage PPF1 is the first temperate phage infecting members of the genus Rhizobium for which a complete genome sequence, as well as other biological data such as the integration site, is available. PMID- 26377944 TI - Relationship between soluble intercellular adhesion molecules and attention deficit/hyperactivity disorder. AB - OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) is a common childhood oneset psychiatric disease, characterized by excessive overactivity, inattention, and impulsiveness. In recent studies, it is emphasized that inflammation may have a role in ADHD. In this study, we aimed to investigate whether there are associations between ADHD and serum levels of soluble intercellular adhesion molecules (s-ICAMs) which have important role in inflammatory diseases. We also measured the levels of these molecules after treatment with oros-methylphenidate. METHODS: Twenty-five patients diagnosed with ADHD according to Diagnostic and Statistical Manual of Mental Disorders-IV-TR criteria and 18 healthy volunteer controls were included in this study. The levels of sICAMs were measured in the serum of the patients and healthy volunteers by ELISA kit as described. RESULTS: The levels of sICAM-1 and sICAM-2 were significantly higher in patients compared with controls. The level of sICAM-2 was decreased significantly in group treated with oros-methylphenidate. CONCLUSIONS: This is the first study pointing out the relationship between sICAMs and ADHD. The changes in sICAM-2 level may have a role in the effect mechanism of oros-methylphenidate, used for the treatment of ADHD. PMID- 26377945 TI - cis-regulatory analysis of the Drosophila pdm locus reveals a diversity of neural enhancers. AB - BACKGROUND: One of the major challenges in developmental biology is to understand the regulatory events that generate neuronal diversity. During Drosophila embryonic neural lineage development, cellular temporal identity is established in part by a transcription factor (TF) regulatory network that mediates a cascade of cellular identity decisions. Two of the regulators essential to this network are the POU-domain TFs Nubbin and Pdm-2, encoded by adjacent genes collectively known as pdm. The focus of this study is the discovery and characterization of cis-regulatory DNA that governs their expression. RESULTS: Phylogenetic footprinting analysis of a 125 kb genomic region that spans the pdm locus identified 116 conserved sequence clusters. To determine which of these regions function as cis-regulatory enhancers that regulate the dynamics of pdm gene expression, we tested each for in vivo enhancer activity during embryonic development and postembryonic neurogenesis. Our screen revealed 77 unique enhancers positioned throughout the noncoding region of the pdm locus. Many of these activated neural-specific gene expression during different developmental stages and many drove expression in overlapping patterns. Sequence comparisons of functionally related enhancers that activate overlapping expression patterns revealed that they share conserved elements that can be predictive of enhancer behavior. To facilitate data accessibility, the results of our analysis are catalogued in cisPatterns, an online database of the structure and function of these and other Drosophila enhancers. CONCLUSIONS: These studies reveal a diversity of modular enhancers that most likely regulate pdm gene expression during embryonic and adult development, highlighting a high level of temporal and spatial expression specificity. In addition, we discovered clusters of functionally related enhancers throughout the pdm locus. A subset of these enhancers share conserved elements including sequences that correspond to known TF DNA binding sites. Although comparative analysis of the nubbin and pdm-2 encoding sequences indicate that these two genes most likely arose from a duplication event, we found only partial evidence of sequence duplication between their enhancers, suggesting that after the putative duplication their cis regulatory DNA diverged at a higher rate than their coding sequences. PMID- 26377946 TI - Deconstructing "Atypical" Eating Disorders: an Overview of Emerging Eating Disorder Phenotypes. AB - Recent changes to the diagnostic framework of eating disorders (ED's) in DSM-5 were introduced to reduce the large preponderance of cases falling within the residual and undifferentiated category. However, current reports continue to illustrate overrepresentation of cases in this residual category, suggesting that clinical reality comprises more diverse ED psychopathology than is accounted for in the current diagnostic spectrum. However, with emerging evidence preliminarily delineating several additional distinct phenotypes, we aim to provide a narrative overview of emerging ED phenotypes which (i) are not currently located as a specific diagnostic category in diagnostic criteria for ED's, (ii) centrally feature ED psychopathology, and (iii) have emerging empirical evidence suggesting the distinct nature of the syndrome. A greater awareness of these emerging phenotypes will likely facilitate accurate diagnostic practice and may also serve to facilitate further empirical efforts. PMID- 26377948 TI - Blogging and Social Media for Mental Health Education and Advocacy: a Review for Psychiatrists. AB - We live in a digital age where information can be found instantaneously via the Internet. Studies have shown that consumers search for much of their medical information on the Internet, particularly utilizing blogs and social media platforms. As the mental health field is riddled with misinformation and stigma, this offers a unique opportunity for psychiatrists and mental health professionals to reach a broad audience for mental health education and advocacy. In this review, we discuss the various methods and techniques for blogging and social media. We then review the current recommendations for ethics and professionalism as well as make recommendations to strengthen our guidance in this new and evolving field. PMID- 26377949 TI - Does muscle coactivation influence joint excursions during gait in children with and without hemiplegic cerebral palsy? Relationship between muscle coactivation and joint kinematics. AB - BACKGROUND: The theoretical role of muscle coactivation is to stiffen joints. The aim of this study was to assess the relationship between muscle coactivation and joint excursions during gait in children with and without hemiplegic cerebral palsy. METHODS: Twelve children with hemiplegic cerebral palsy and twelve typically developing children underwent gait analysis at three different gait speeds. Sagittal hip, knee, and ankle kinematics were divided into their main components corresponding to joint excursions. A coactivation index was calculated for each excursion from the electromyographic envelopes of the rectus femoris/semitendinosus, vastus medialis/semitendinosus, or tibialis anterior/soleus muscles. Mixed linear analyses of covariance modeled joint excursions as a function of the coactivation index and limb. FINDINGS: In typically developing children, increased coactivation was associated with reduced joint excursion for 8 of the 14 linear models (hip flexion, knee loading, knee extension in stance, knee flexion in swing, ankle plantarflexion from initial contact to foot-flat, ankle dorsiflexion in stance and in swing). Conversely, ankle plantarflexion excursion at push-off increased with increasing tibialis anterior/soleus coactivation. In the involved limbs of the children with cerebral palsy, knee loading, ankle plantarflexion at push off, and ankle dorsiflexion in swing decreased, while hip extension increased, with increasing muscle coactivation. INTERPRETATION: The relationships between muscle coactivation and joint excursion were not equally distributed in both groups, and predominant in typically developing children. The results suggest that excessive muscle coactivation is not a cause of stiff-knee gait in children with hemiplegic cerebral palsy, but appears to be related to spastic drop foot. PMID- 26377950 TI - The Influence of Surface Modification on the Photoluminescence of CdTe Quantum Dots: Realization of Bio-Imaging via Cost-Effective Polymer. AB - To impart biocompatibility, stability, and specificity to quantum dots (QDs)-and to reduce their toxicity-it is essential to carry out surface modification. However, most surface-modification processes are costly, complicated, and time consuming. In addition, the modified QDs often have a large size, which leads to easy aggregation in biological environments, making it difficult to excrete them from in vivo systems. To solve these problems, three kinds of conventional polymers, namely, polyvinyl alcohol (PVA, neutral), sodium polystyrene sulfonate (PSS, negative charged), and poly(diallyl dimethyl ammonium chloride) (PDDA, positive charged) were selected to modify the surface of QDs at low cost via a simple process in which the size of the QDs was kept small after modification. The effect of polymer modification on the photoluminescence (PL) properties of the QDs was systematically investigated. High quantum yields (QYs) of 65 % were reached, which is important for the realization of bio-imaging. Then, the cytotoxicity of CdTe QD-polymer composites was systematically investigated via MTT assay using the Cal27 and HeLa cell lines, especially for high concentrations of QD-polymer composites in vitro. The experimental results showed that the cytotoxicity decreased in the order CdTe-PDDA>CdTe>CdTe-PSS>CdTe-PVA, indicating that PSS and PVA can reduce the toxicity of the QDs. An obvious cytotoxicity of CdTe-PVA and CdTe-PSS was present until 120 h for the Cal27 cell line and until 168 h for the HeLa cell line. At last, the Cal27 cell line was selected to realize bio-imaging using CdTe-PSS and CdTe-PVA composites with different emission colors under one excitation wavelength. PMID- 26377947 TI - Premenstrual Dysphoric Disorder: Epidemiology and Treatment. AB - Recently designated as a disorder in the DSM-5, premenstrual dysphoric disorder (PMDD) presents an array of avenues for further research. PMDD's profile, characterized by cognitive-affective symptoms during the premenstruum, is unique from that of other affective disorders in its symptoms and cyclicity. Neurosteroids may be a key contributor to PMDD's clinical presentation and etiology, and represent a potential avenue for drug development. This review will present recent literature on potential contributors to PMDD's pathophysiology, including neurosteroids and stress, and explore potential treatment targets. PMID- 26377951 TI - Study shows higher risk from hip fracture surgery than hip replacement even after adjustment for age. PMID- 26377952 TI - Health information needs, sources, and barriers of primary care patients to achieve patient-centered care: A literature review. AB - : To synthesize findings from previous studies assessing information needs of primary care patients on the Internet and other information sources in a primary care setting. A systematic review of studies was conducted with a comprehensive search in multiple databases including OVID MEDLINE, CINAHL, and Scopus. The most common information needs among patients were information about an illness or medical condition and treatment methods, while the most common information sources were the Internet and patients' physicians. Overall, patients tend to prefer the Internet for the ease of access to information, while they trust their physicians more for their clinical expertise and experience. Barriers to information access via the Internet include the following: socio-demographic variables such as age, ethnicity, income, education, and occupation; information search skills; and reliability of health information. CONCLUSION: Further research is warranted to assess how to create accurate and reliable health information sources for both Internet and non-Internet users. PMID- 26377953 TI - Indirect costs of absenteeism due to rheumatoid arthritis, psoriasis, multiple sclerosis, insulin-dependent diabetes mellitus, and ulcerative colitis in 2012: a study based on real-life data from the Social Insurance Institution in Poland. AB - INTRODUCTION: The aim of this study is to assess the indirect costs of six major autoimmune diseases including seropositive rheumatoid arthritis, other types of rheumatoid arthritis, psoriasis, multiple sclerosis, Type 1 diabetes, and ulcerative colitis. METHODS: Relevant data for 2012 on sick leave and short- and long-term work disabilities were obtained from the Social Insurance Institution in Poland. Indirect costs were estimated using the human capital approach based on gross domestic product per capita, gross value added per worker, and gross income per worker in Poland in 2012 and expressed in euro. RESULTS: We recorded data on the total number of 45,500 patients. The total indirect costs were EUR 146,862,569; 353,683,508; and 108,154,271, calculated using gross domestic product, gross value added, and gross income, respectively. CONCLUSIONS: Considering only data on absenteeism collected by the Social Insurance Institution in Poland, we can conclude that the selected autoimmune diseases are associated with great indirect costs. PMID- 26377954 TI - Seeking the sun in deep, dark places: mesopelagic sightings of ocean sunfishes (Molidae). AB - Evidence is presented from publicly available remotely operated vehicle (ROV) footage that suggests deep-water ranging in ocean sunfishes (family Molidae) is more common than typically thought, including a new maximum depth recorded for the southern sunfish Mola ramsayi. PMID- 26377955 TI - Parker et al. Respond to "Preeclampsia Risk After Induced Abortion". PMID- 26377956 TI - Invited Commentary: Induced Abortion and the Risk of Preeclampsia in a Subsequent Pregnancy. AB - Although it is well established that a having a pregnancy that ends in a birth protects against subsequent preeclampsia, it is unclear whether a pregnancy ending in miscarriage or induced abortion confers any protection. In this issue of the Journal, Parker et al. (Am J Epidemiol. 2015;182(8):663-669) examine whether, in nulliparous women, a history of induced abortion is associated with a lower risk of preeclampsia in a later pregnancy, focusing on the hypothesis that endometrial injury facilitates later implantation. The authors take advantage of data obtained by linking several Finnish population-based registries that include detailed data on induced abortions, although information on miscarriages was of lower quality. Parker et al. found a modest reduction in risk among women with a history of induced abortion. However, there was little evidence that risk differed between women who had medical abortions and those who had surgical abortions (the latter of which is presumably associated with a higher degree of injury). History of miscarriage was not associated with preeclampsia risk. Although the study by Parker et al. adds to the evidence that suggests that women with a history of induced abortion have a lower risk of preeclampsia, it is difficult to evaluate whether the observed association is due to having had a previous pregnancy (however short) versus none, to confounding, or to an actual effect of induced abortion. PMID- 26377957 TI - Induced Abortions and the Risk of Preeclampsia Among Nulliparous Women. AB - Induced abortion (IA) has been associated with a lower risk of preeclampsia among nulliparous women, but it remains unclear whether this association differs by method (either surgical or medical) or timing of IA. We performed a nested case control study of 12,650 preeclampsia cases and 50,600 matched control deliveries identified in the Medical Birth Register of Finland from 1996 to 2010. Data on number, method, and timing of IAs were obtained through a linkage with the Registry of Induced Abortions. Odds ratios and 95% confidence intervals were calculated. Overall, prior IA was associated with a lower risk of preeclampsia, with odds ratios of 0.9 (95% confidence interval (CI): 0.9, 1.0) for 1 prior IA and 0.7 (95% CI: 0.5, 1.0) for 3 or more IAs. Differences in the associations between IA and preeclampsia by timing and method of IA were small, with odds ratios of 0.8 (95% CI: 0.6, 1.1) for late (>=12 gestation weeks) surgical abortion and 0.9 (95% CI: 0.7, 1.2) for late medical abortion. There was no association between IA in combination with a history of spontaneous abortion and risk of preeclampsia. In conclusion, prior IA only was associated with a slight reduction in the risk of preeclampsia. PMID- 26377958 TI - Residential Proximity to Heavy-Traffic Roads, Benzene Exposure, and Childhood Leukemia-The GEOCAP Study, 2002-2007. AB - Childhood leukemia may be associated with traffic-related environmental exposure to benzene, and additional data are needed. The Geolocalisation des Cancers Pediatriques (GEOCAP) Study, a nationwide French case-control study, was designed to avoid selection bias due to differential participation and misclassification. The study compared the 2,760 childhood leukemia cases diagnosed in France between 2002 and 2007 (including 2,275 cases of acute lymphoblastic leukemia (ALL) and 418 cases of acute myeloblastic leukemia (AML)) with 30,000 contemporaneous child population controls. The residence addresses were precisely geocoded, and 3 indicators of residential proximity to traffic were considered. Estimates of benzene concentrations were also available for the Ile-de-France region (including Paris). A 300-m increase in major road length within 150 m of the geocoded address was significantly associated with AML (odds ratio = 1.2, 95% confidence interval: 1.0, 1.4) but not with ALL (odds ratio = 1.0, 95% confidence interval: 0.9, 1.1), and the association was reinforced in the Ile-de-France region when this indicator was combined with benzene estimates. These results, which were free from any participation bias and based on objectively determined indices of exposure, showed an increased incidence of AML associated with heavy traffic road density near a child's home. The results support a role for traffic related benzene exposure in the etiology of childhood AML. PMID- 26377959 TI - Exact Inference for Hardy-Weinberg Proportions with Missing Genotypes: Single and Multiple Imputation. AB - This paper addresses the issue of exact-test based statistical inference for Hardy-Weinberg equilibrium in the presence of missing genotype data. Missing genotypes often are discarded when markers are tested for Hardy-Weinberg equilibrium, which can lead to bias in the statistical inference about equilibrium. Single and multiple imputation can improve inference on equilibrium. We develop tests for equilibrium in the presence of missingness by using both inbreeding coefficients (or, equivalently, chi(2) statistics) and exact p-values. The analysis of a set of markers with a high missing rate from the GENEVA project on prematurity shows that exact inference on equilibrium can be altered considerably when missingness is taken into account. For markers with a high missing rate (>5%), we found that both single and multiple imputation tend to diminish evidence for Hardy-Weinberg disequilibrium. Depending on the imputation method used, 6-13% of the test results changed qualitatively at the 5% level. PMID- 26377960 TI - LinkImpute: Fast and Accurate Genotype Imputation for Nonmodel Organisms. AB - Obtaining genome-wide genotype data from a set of individuals is the first step in many genomic studies, including genome-wide association and genomic selection. All genotyping methods suffer from some level of missing data, and genotype imputation can be used to fill in the missing data and improve the power of downstream analyses. Model organisms like human and cattle benefit from high quality reference genomes and panels of reference genotypes that aid in imputation accuracy. In nonmodel organisms, however, genetic and physical maps often are either of poor quality or are completely absent, and there are no panels of reference genotypes available. There is therefore a need for imputation methods designed specifically for nonmodel organisms in which genomic resources are poorly developed and marker order is unreliable or unknown. Here we introduce LinkImpute, a software package based on a k-nearest neighbor genotype imputation method, LD-kNNi, which is designed for unordered markers. No physical or genetic maps are required, and it is designed to work on unphased genotype data from heterozygous species. It exploits the fact that markers useful for imputation often are not physically close to the missing genotype but rather distributed throughout the genome. Using genotyping-by-sequencing data from diverse and heterozygous accessions of apples, grapes, and maize, we compare LD-kNNi with several genotype imputation methods and show that LD-kNNi is fast, comparable in accuracy to the best-existing methods, and exhibits the least bias in allele frequency estimates. PMID- 26377961 TI - Erratum to: The collective nuclear migration of p53 and phosphorylated S473 of Akt during ellipticine-mediated apoptosis in human lung epithelial cancer cells. PMID- 26377962 TI - Identification and Characterization of Hypoxia-Regulated Endothelial Circular RNA. AB - RATIONALE: Circular RNAs (circRNAs) are noncoding RNAs generated by back splicing. Back splicing has been considered a rare event, but recent studies suggest that circRNAs are widely expressed. However, the expression, regulation, and function of circRNAs in vascular cells is still unknown. OBJECTIVE: Here, we characterize the expression, regulation, and function of circRNAs in endothelial cells. METHODS AND RESULTS: Endothelial circRNAs were identified by computational analysis of ribo-minus RNA generated from human umbilical venous endothelial cells cultured under normoxic or hypoxic conditions. Selected circRNAs were biochemically characterized, and we found that the majority of them lacks polyadenylation, is resistant to RNase R digestion and localized to the cytoplasm. We further validated the hypoxia-induced circRNAs cZNF292, cAFF1, and cDENND4C, as well as the downregulated cTHSD1 by reverse transcription polymerase chain reaction in cultured endothelial cells. Cloning of cZNF292 validated the predicted back splicing of exon 4 to a new alternative exon 1A. Silencing of cZNF292 inhibited cZNF292 expression and reduced tube formation and spheroid sprouting of endothelial cells in vitro. The expression of pre-mRNA or mRNA of the host gene was not affected by silencing of cZNF292. No validated microRNA binding sites for cZNF292 were detected in Argonaute high-throughput sequencing of RNA isolated by cross-linking and immunoprecipitation data sets, suggesting that cZNF292 does not act as a microRNA sponge. CONCLUSIONS: We show that the majority of the selected endothelial circRNAs fulfill all criteria of bona fide circRNAs. The circRNA cZNF292 exhibits proangiogenic activities in vitro. These data suggest that endothelial circRNAs are regulated by hypoxia and have biological functions. PMID- 26377963 TI - Is acute reperfusion therapy safe in acute ischemic stroke patients who harbor unruptured intracranial aneurysm? AB - BACKGROUND: Intracranial aneurysms are currently considered as contraindication for intravenous thrombolysis in acute ischemic stroke, very likely due to a possible increase in the risk of bleeding from aneurysm rupture; however, there is limited data available on whether intravenous thrombolysis is safe for acute ischemic stroke patients with pre-existing intracranial aneurysms. AIMS AND/OR HYPOTHESIS: To find out the safety of intravenous thrombolysis in acute ischemic stroke patients who harbor unruptured intracranial aneurysms. METHODS: We retrospectively reviewed the medical records and cerebrovascular images of all the patients treated with intravenous thrombolysis for acute ischemic stroke in our center from the beginning of 2006 till the end of April 2014. Those with unruptured intracranial aneurysm present on cerebrovascular images prior to acute reperfusion therapy were identified. Post-thrombolysis brain imaging was reviewed to evaluate for any intraparenchymal or subarachnoid hemorrhage related or unrelated to the aneurysm. RESULTS: A total of 637 patients received intravenous thrombolysis for acute ischemic stroke in our center during an 8.3-year period. Thirty-three (5.2%) were found to have at least one intracranial aneurysms. Twenty-three (70%) of those received only intravenous thrombolysis, and 10 patients received combination of intravenous and intra-arterial thrombolysis. The size of the largest aneurysm was 10 mm in maximum diameter (range: 2-10 mm). The mean size of aneurysms was 4.8 mm. No symptomatic intracranial hemorrhage occurred among the 23 patients receiving only intravenous thrombolysis. Out of those who received a combination of intravenous and intra-arterial thrombolysis, one developed symptomatic intracranial hemorrhage in the location of acute infarct, distant to the aneurysm location. CONCLUSION: Our findings suggest that neither intravenous thrombolysis nor combination of intravenous and intra arterial thrombolysis increases the risk of aneurysmal hemorrhage in acute ischemic stroke patients who harbor unruptured intracranial aneurysms less than 10 mm in diameter. Their listing in exclusion criteria for intravenous thrombolysis should be reconsidered to assure appropriate use of acute reperfusion therapy in this group of patients. PMID- 26377964 TI - Optimization and Scale-up Isolation and Culture of Neonatal Porcine Islets: Potential for Clinical Application. AB - One challenge that must be overcome to allow transplantation of neonatal porcine islets (NPIs) to become a clinical reality is defining a reproducible and scalable protocol for the efficient preparation of therapeutic quantities of clinical grade NPIs. In our standard protocol, we routinely isolate NPIs from a maximum of four pancreases, requiring tissue culture in 16 Petri dishes (four per pancreas) in Ham's F10 and bovine serum albumin (BSA). We have now developed a scalable and technically simpler protocol that allows us to isolate NPIs from a minimum of 12 pancreases at a time by employing automated tissue chopping, collagenase digestion in a single vessel, and tissue culture/media changes in 75% fewer Petri dishes. For culture, BSA is replaced with human serum albumin and supplemented with Z-VAD-FMK general caspase inhibitor and a protease inhibitor cocktail. The caspase inhibitor was added to the media for only the first 90 min of culture. NPIs isolated using the scalable protocol had significantly more cellular insulin recovered (56.9 +/- 1.4 ug) when compared to the standard protocol (15.0 +/- 0.5 ug; p < 0.05). Compared to our standard protocol, recovery of beta-cells (6.0 * 10(6) +/- 0.2 vs. 10.0 * 10(6) +/- 0.4; p < 0.05) and islet equivalents (35,135 +/- 186 vs. 41,810 +/- 226; p < 0.05) was significantly higher using the scalable protocol. During a static glucose stimulation assay, the SI of islets isolated by the standard protocol were significantly lower than the scale-up protocol (4.3 +/- 0.2 vs. 5.5 +/- 0.1; p < 0.05). Mice transplanted with NPIs using the scalable protocol had significantly lower blood glucose levels than the mice that receiving NPIs from the standard protocol (p < 0.01) and responded significantly better to a glucose tolerance test. Based on the above findings, this improved simpler scalable protocol is a significantly more efficient means for preparing therapeutic quantities of clinical grade NPIs. PMID- 26377965 TI - Fast determination of 24 steroid hormones in river water using magnetic dispersive solid phase extraction followed by liquid chromatography-tandem mass spectrometry. AB - The easiness-to-handle of the magnetic dispersive solid phase extraction (Mag dSPE) procedure was developed for preconcentration of 24 steroid hormones in river water. Ethylenediamine-functionalized magnetic carbon nanotubes (EDA@Mag CNTs) were synthesised by a simple one-pot reaction and were used as sorbent in Mag-dSPE procedure. The properties of the EDA@Mag-CNTs were characterized by transmission electron microscopy (TEM) and vibrating sample magnetometer (VSM). An ultra-fast liquid chromatography-tandem quadrupole mass spectrometry (UFLC MS/MS) method for determination of 24 steroid hormones in river water at nanograms per liter had been developed with pretreatment of the samples by Mag dSPE. The obtained results demonstrated the higher extraction capacity of EDA@Mag CNT Mag-dSPE with recoveries between 82.1 and 113%. The limits of quantification (LOQs) for the steroid hormone were between 0.020 and 1.00 ng/L. The developed method had been successfully applied to 60 river water samples, and it was confirmed that EDA@Mag-CNT Mag-dSPE was a highly effective extraction method for the steroid hormone analyses. PMID- 26377966 TI - Thermal degradation of polybrominated diphenyl ethers over as-prepared Fe3O4 micro/nano-material and hypothesized mechanism. AB - The thermal degradation of decabromodiphenyl ether (BDE-209) featuring fully substituted bromines was investigated over an as-prepared Fe3O4 micro/nano material at 300 degrees C. Degradation followed pseudo-first-order kinetics with kobs = 0.15 min(-1) higher than that for decachlorobiphenyl (CB-209). Twenty-six newly produced polybrominated diphenyl ether (PBDE) congeners were identified using the available PBDE standards, while four PBDE congener products were predicted using third-order polynomial regression equation. Analysis of the products indicated that BDE-209 underwent stepwise hydrodebromination over as prepared Fe3O4. Similar to the case for CB-209, two initial hydrodebromination steps are favored at the BDE-209 meta-positions, giving the major products BDE 207 and BDE-197. However, the variance about the preferred products began to emerge from the start of heptabromodiphenyl ethers (hepta-BDEs). The majorly produced hepta-BDE isomer with BDE-183 is unbrominated at one ortho-position. However, this is different from the reported degradation of CB-209, which always produced the products chlorinated at all four ortho-positions until the ortho position had to be removed for the formation of trichlorobiphenyls and dichlorobiphenyl still majorly chlorinated at three or two ortho-positions. The early BDE-209 hydrodebromination steps appear to be strongly influenced by steric effects, whereas subsequent hydrodebromination steps, as more bromine atoms are removed, will be gradually governed more by thermodynamics. PMID- 26377967 TI - Spatial and temporal variability in nitrous oxide and methane emissions in urban riparian zones of the Pearl River Delta. AB - Spatial and temporal variability in nitrous oxide and methane emissions were quantified in three seasons using closed chambers in three riparian zone locations of three branches of the Pearl River, Guangzhou, China. The sampling sites were selected in a rapidly developing urban area of Guangzhou and represented a pollution gradient. The results show that urban riparian landscapes can be large source areas for CH4 and N2O, with fluxes of -0.035~32.30 mg m(-2) h(-1) and -5.49~37.31 MUg m(-2) h(-1), respectively. River water quality, sediment texture, and NH4-N and NO3-N concentrations correlated with N2O and CH4 emission rates. The riparian zones of the more seriously polluted tributaries showed higher greenhouse gas fluxes than that of the less polluted main stem of the Pearl River. Rain events increased emissions of CH4 by 6.5~21.3 times and N2O by 2.2~5.7 times. The lower concentrations of heavy metals increased the activity of denitrifying enzymes while inhibited the methane producing pathways. This work demonstrates that rapidly developing urban areas are an important source of greenhouse gas emissions, which is conditioned by various environmental factors. PMID- 26377968 TI - Effect of lambda cyhalothrin on Calothrix sp. (GUEco 1001), an autochthonous cyanobacterium of rice fields of Brahmaputra floodplain. AB - Pesticide contamination in the rice fields has manifested into a serious global environmental concern. Application of pesticides in the rice fields has deleterious effects on non-target organisms including nitrogen-fixing cyanobacteria which help to maintain the rice field fertility. In the present research endeavor, the effect of lambda cyhalothrin (5% EC), a synthetic pyrethroid insecticide, has been studied on the growth and pigments content of Calothrix sp. (GUEco 1001), an indigenous strain isolated from rice grown areas of Brahmaputra floodplain. To study the toxic effect of lambda cyhalothrin, the test organism was exposed to varying concentrations of the insecticide i.e., 20 ppm, 40 ppm, 80 ppm, and 160 ppm based upon the determination of LC50 for a period of 20 days. The result obtained in the laboratory showed a progressive decrease in the growth and pigments content by the test organism with increasing concentrations of the lambda cyhalothrin against time dose-dependent manner. At high dose (160 ppm), the test organism showed significant decrease in dry weight biomass (54.5%), chlorophyll-a (68%), carotenoids (38%), phycocyanin (80%), and nitrogen contents (55%) over the control. A little but insignificant stimulatory effect on growth and chlorophyll-a contents was recorded in 20 ppm treatment of the insecticide that, however, was reversed in case of carotenoids and phycocyanin contents. PMID- 26377969 TI - Organic fraction of municipal solid waste from mechanical selection: biological stabilization and recovery options. AB - Although current trends address towards prevention strategies, the organic fraction of municipal solid waste is greatly produced, especially in high-income contexts. Its recovery-oriented collection is a common practice, but a relevant portion of the biodegradable waste is not source selected. Mechanical and biological treatments (MBT) are the most common option to sort and stabilize the biodegradable matter ending in residual waste stream. Following the changes of the framework around waste management, this paper aimed at analyzing the quality of the mechanically selected organic waste produced in MBT plants, in order to discuss its recovery options. The material performance was obtained by its composition as well as by its main chemical and physical parameters; biological stability was also assessed by both aerobic and anaerobic methods. On this basis, the effectiveness of an aerobic biostabilization process was assessed at pilot scale. After 21 days of treatment, results proved that the biomass had reached an acceptable biostabilization level, with a potential Dynamic Respirometric Index (DRIP) value lower than the limit required for its use as daily or final landfill cover material. However, the final stabilization level was seen to be influenced by scaling factors and the 21 days of treatment turned to be not so adequate when applied in the existing full-scale facility. PMID- 26377970 TI - Effects of operating conditions on trihalomethanes formation and speciation during chloramination in reclaimed water. AB - In this study, a hybrid powdered activated carbon-membrane bioreactor (PAC-MBR) system was used to treat municipal wastewater in northern China intended for recycle. In order to control microbiological hazards in PAC-MBR effluent, chloramine was chosen as the disinfectant which could reduce the disinfection by product yields. Effects of reaction time, chloramines dose, pH value, and bromide ion concentration on trihalomethanes (THMs) formation and speciation during chloramination of the reclaimed effluent were investigated. Study results indicated that the yield of total THMs (TTHM) increased at higher reaction time and chloramines dose. The trend of growth showed that slow reacting precursors were the main components of dissolved organic matter (DOM) in PAC-MBR effluent. THMs formation potential of PAC-MBR effluent achieved the maximum at chloramines dosage of 20 mg/L. Meanwhile, THMs formation was enhanced evidently under alkaline conditions. The yields of THMs species were in following order: CHCl3 > CHBrCl2 > CHBr2Cl > CHBr3, although in different reaction time, chloramines dose, and pH value. Furthermore, the formation of Br-THMs was promoted by the increasing concentration of bromide ion. PMID- 26377971 TI - Homogeneous static magnetic field of different orientation induces biological changes in subacutely exposed mice. AB - It has been shown that static magnetic field (SMF) of moderate intensity produces considerable impact on biological systems. SMF can be homogeneous or inhomogeneous. In many studies, inhomogeneous SMF was employed. Aware that inhomogeneous SMF could result in experimental variability, we investigated the influence of a vertical homogeneous SMF of different orientation. Male Swiss Webster 9- to 10-week-old mice were subacutely exposed to upward- and downward oriented SMF of 128 mT generated by a cyclotron for 1 h/day during a 5-day period. We found that SMF affected various organs and that these effects were, to some degree, dependent on SMF orientation. Both upward- and downward-oriented SMF caused a reduction in the amount of total white blood cells (WBC) and lymphocytes in serum, a decrease of granulocytes in the spleen, kidney inflammation, and an increase in the amount of high-density lipoprotein (HDL). In addition, upward oriented SMF caused brain edema and increased spleen cellularity. In contrast, downward-oriented SMF induced liver inflammation and a decrease in the amount of serum granulocytes. These effects might represent a specific redistribution of pro-inflammatory cells in blood and among various organs. It appears that homogeneous SMF of 128 mT affected specific organs in the body, rather than simultaneously and equally influencing the entire body system. PMID- 26377972 TI - Model-based analysis of the effect of different operating conditions on fouling mechanisms in a membrane bioreactor. AB - This study proposes a model-based evaluation of the effect of different operating conditions with and without pre-denitrification treatment and applying three different solids retention times on the fouling mechanisms involved in membrane bioreactors (MBRs). A total of 11 fouling models obtained from literature were used to fit the transmembrane pressure variations measured in a pilot-scale MBR treating real wastewater for more than 1 year. The results showed that all the models represent reasonable descriptions of the fouling processes in the MBR tested. The model-based analysis confirmed that membrane fouling started by pore blocking (complete blocking model) and by a reduction of the pore diameter (standard blocking) while cake filtration became the dominant fouling mechanism over long-term operation. However, the different fouling mechanisms occurred almost simultaneously making it rather difficult to identify each one. The membrane "history" (i.e. age, lifespan, etc.) seems the most important factor affecting the fouling mechanism more than the applied operating conditions. Nonlinear regression of the most complex models (combined models) evaluated in this study sometimes demonstrated unreliable parameter estimates suggesting that the four basic fouling models (complete, standard, intermediate blocking and cake filtration) contain enough details to represent a reasonable description of the main fouling processes occurring in MBRs. PMID- 26377973 TI - Movement-based subgrouping in low back pain: synergy and divergence in approaches. PMID- 26377975 TI - Efficacy but not effectiveness of sublingual immunotherapy for grass pollen allergy: Time to avoid waste in health-care expenditure. PMID- 26377976 TI - The impact of advancing age on postoperative outcomes in plastic surgery. AB - Age has been shown to be an independent predictor of complications in general surgery patients. In contrast, the effect of age on outcomes after plastic surgery has yet to be confirmed or refuted. The objective of the current investigation was to evaluate a possible association between age and postoperative outcomes after plastic surgery. The 2005-2012 NSQIP database was retrospectively reviewed for all patients undergoing plastic surgery. Patients >=60 years with procedures under the category of plastic surgery in NSQIP were selected for analysis. The primary outcome of interest was 30-day overall complication rates. Multivariate regression models were constructed to control for potential perioperative confounders. Of the 2,320,920 patients captured in the NSQIP database, 36,819 patients underwent plastic surgery and met inclusion criteria. The incidence of unadjusted overall complications increased with age with an overall complication rate of 9.0% in patients <60 years, 11.6% in patients 60-69 years, 13.2% in patients 70-79 years, and 15.9% in patients 80 or more years (p < 0.001). After adjusting for potential confounders, age was not independently associated with increased overall complications rates in patients 60-69 years (OR = 1.026; 95% CI = 0.927-1.135; p = 0.619) and 70-79 years (OR = 0.933; 95% CI = 0.797-0.919; p = 0.393), although patients 80 years and older experienced more medical complications (OR = 1.626; 95% CI = 1.218-2.172; p = 0.001). Age is not independently associated with overall worse outcomes in patients undergoing plastic surgery. Medical complications and mortality were more likely in extremes of age (>80 years). Age alone should not be included as a decisional factor in patients <80 years old considering plastic surgery. PMID- 26377974 TI - CD151-alpha3beta1 integrin complexes are prognostic markers of glioblastoma and cooperate with EGFR to drive tumor cell motility and invasion. AB - Glioblastoma, one of the most aggressive forms of brain cancer, is featured by high tumor cell motility and invasiveness, which not only fuel tumor infiltration, but also enable escape from surgical or other clinical interventions. Thus, better understanding of how these malignant traits are controlled will be key to the discovery of novel biomarkers and therapies against this deadly disease. Tetraspanin CD151 and its associated alpha3beta1 integrin have been implicated in facilitating tumor progression across multiple cancer types. How these adhesion molecules are involved in the progression of glioblastoma, however, remains largely unclear. Here, we examined an in-house tissue microarray-based cohort of 96 patient biopsies and TCGA dataset to evaluate the clinical significance of CD151 and alpha3beta1 integrin. Functional and signaling analyses were also conducted to understand how these molecules promote the aggressiveness of glioblastoma at molecular and cellular levels. Results from our analyses showed that CD151 and alpha3 integrin were significantly elevated in glioblastomas at both protein and mRNA levels, and exhibited strong inverse correlation with patient survival (p < 0.006). These adhesion molecules also formed tight protein complexes and synergized with EGF/EGFR to accelerate tumor cell motility and invasion. Furthermore, disruption of such complexes enhanced the survival of tumor-bearing mice in a xenograft model, and impaired activation of FAK and small GTPases. Also, knockdown- or pharmacological agent-based attenuation of EGFR, FAK or Graf (ARHGAP26)/small GTPase-mediated pathways markedly mitigated the aggressiveness of glioblastoma cells. Collectively, our findings provide clinical, molecular and cellular evidence of CD151-alpha3beta1 integrin complexes as promising prognostic biomarkers and therapeutic targets for glioblastoma. PMID- 26377977 TI - Pressure and tendon strain in the sixth extensor compartment of the wrist during simulated provocative maneuvers for diagnosing extensor carpi ulnaris tendinitis. AB - BACKGROUND: Various provocative maneuvers for diagnosing extensor carpi ulnaris (ECU) tendinitis have been reported; however, it remains unclear which maneuver is the most sensitive to detect ECU tendinitis. To clarify this, we investigated and compared the extratendinous pressure and ECU tendon strain in the sixth extensor compartment of the wrist during various provocative maneuvers for diagnosing ECU tendinitis. METHODS: Nine upper extremities from nine fresh-frozen cadavers were examined. We investigated extratendinous pressure in the ECU fibro osseous tunnel of the distal ulna and ECU tendon strain during eight forearm positions-neutral rotation, pronation, supination, pronation with wrist flexion, supination with wrist flexion, supination with wrist extension, both hand and forearm supination, and supination with ECU full loading-to simulate provocative maneuvers reported to detect ECU tendinitis. RESULTS: Pressure was significantly higher during both hand and forearm supination (carpal supination test) and during supination with wrist extension (prayer's hand supination test) than during neutral rotation. The pressure during the carpal supination test was 3 times higher than that during the prayer's hand supination test and 27 times higher than that during the neutral position. Strain was significantly higher during the carpal supination test and during supination with ECU full loading (the ECU synergy test) than during other maneuvers. CONCLUSIONS: Both pressure and tendon strain increased most notably during the carpal supination test compared to the other maneuvers, which suggests that the carpal supination test is the most sensitive for the detection of ECU tendinitis. PMID- 26377978 TI - The sociality of bioremediation: Hijacking the social lives of microbial populations to clean up heavy metal contamination. PMID- 26377979 TI - First-Step Results of Children Presenting with Bleeding Symptoms or Abnormal Coagulation Tests in an Outpatient Clinic. AB - OBJECTIVE: Mild bleeding symptoms are commonly seen in the general population. The aim of this study was to determine the final clinical and laboratory features of children referred for a first evaluation with a suspected bleeding disorder in the pediatric outpatient clinic of Istanbul University. MATERIALS AND METHODS: The medical records of 26,737 outpatients who were admitted to the Division of Ambulatory Pediatrics between 31 October 2011 and 31 October 2012 were evaluated retrospectively. Ninety-nine patients were initially diagnosed as having probable bleeding disorders and were followed up. The symptoms of bleeding in addition to coagulation tests were analyzed. RESULTS: Of the 99 patients, 52 (52.5%) were male and 47 were female, and the mean age of the entire study group was 9.1+/-4.1 years (minimum-maximum: 2-18 years). Major bleeding symptoms were epistaxis in 36 patients (36.4%), easy bruising in 32 (32.3%), and menorrhagia in 6 (6.1%). After initial tests ordered by the pediatrician, 36 of 99 patients (36.4%) were diagnosed as having bleeding disorders that included von Willebrand disease in 12 (12.1%), hemophilia A or B in 9 (9.1%), and other rare factor deficiencies in 9 (9.1%). Six patients (6.1%) were found to have combined deficiencies. Seven of 36 patients had a family history of bleeding. CONCLUSION: Among the patients referred for bleeding disorders, 36.4% were diagnosed with a bleeding disorder with the help of primary screening tests ordered in the outpatient clinic. PMID- 26377980 TI - Strategy for the surgical treatment of vestibular schwannomas in patients with neurofibromatosis type 2. AB - OBJECTIVE: Guidelines for appropriate management of vestibular schwannomas in NF2 patients are controversial. In this paper we reviewed our experience with patients with NF2 for the results of surgical treatment with particular reference to hearing and facial nerve preservation. METHODS: We included in the study 30 patients (16 women and 14 men) with the diagnosis of NF2 treated in our department between 1998 and 2014 who underwent surgery for vestibular schwannoma removal with a follow-up for at least 1 year. In 3 cases, the vestibular schwannomas were unilateral. Six patients with bilateral vestibular schwannomas underwent unilateral procedure. Therefore, 51 acoustic tumors were studied in 30 patients. RESULTS: No operative death we noted. Significant deterioration to the non-functional level occurred in 19 out of 22 cases with well-preserved preoperative hearing. Only three ears maintained their preoperative good hearing. Hearing was preserved in cases of small schwannoma not exceeding 2 cm. Among 21 patients who underwent bilateral operations hearing was preserved in 3 out of 7 cases when smaller tumor or better hearing level side was attempted at first surgery. In contrary none of the 14 patients retained hearing when the first operation concerned the worse-hearing ear. Among 14 tumors up to 2 cm there was only one case of moderately severe facial nerve dysfunction (House-Brackmann Grade IV) in the long follow-up. CONCLUSION: Early surgical intervention for vestibular schwannoma in NF2 patient is a viable management strategy to maintain hearing function and preserve facial nerve function. PMID- 26377981 TI - Articulation disorders and duration, severity and L-dopa dosage in idiopathic Parkinson's disease. AB - BACKGROUND: Parkinson's disease (PD) is one of the most common diseases of the central nervous system (CNS). It is frequently heralded by speech disturbances, which are one of its first symptoms. AIM: The aim of this paper is to share our own experience concerning the correlation between the severity of speech disorders and the PD duration, its severity and the intake of L-dopa. MATERIAL AND METHODS: The research included 93 patients with idiopathic PD, aged 26-86 years (mean age 65.1 years). Participants were examined neurologically according to the Unified Parkinson's Disease Rating Scale (UPDRS) and the Hoehn and Yahr Scale. They were also assessed by Frenchay Dysarthria Assessment. RESULTS: Considerable and severe disorders were concurrent with impairments in the mobility of the tongue, lips, the jaw as well as the pitch and loudness of the voice. The strongest correlation but at a moderate level was found to exist between the severity of labial impairment, voice loudness and the length of the disease. There was also a positive correlation between lip movement while the motions were being diversified, lip arrangement while speaking and the intake of L-dopa. CONCLUSIONS: As PD progresses a significant decline in vocal articulation can be observed, which is due to reduced mobility within the lips and the jaw. Exacerbation of articulation disorders resulting from progression of the disease does not materially influence the UPDRSS scores. L-dopa has been found to positively affect the mobility of the lips while the patient is speaking and their arrangement at rest. PMID- 26377982 TI - Sacral roots stimulation in chronic pelvic pain. AB - INTRODUCTION: Chronic pelvic pain is a syndrome of chronic non-malignant pain of multifactorial pathophysiology. Perineal, anal and coccygeal pain can be a form of failed-back surgery syndrome or complex regional pain syndrome. Apart from conservative treatment interventional methods are useful in this condition as neurolytic blocks or non-destructive neuromodulation procedures. Peripheral nerve, spinal cord stimulation or sacral stimulation can be applied. AIM: We describe a minimally invasive method of sacral roots stimulation with percutaneous electrodes implanted through the sacral hiatus in the treatment of chronic pelvic pain. MATERIALS AND METHODS: We evaluated a series of nine female patients with pelvic pain treated with sacral roots stimulation in regard of efficacy and complications of this method. RESULTS: Short-term results in all patients were satisfactory with statistically significant improvement (median VAS=9 before surgery) (median VAS=2 after implantation, p=0.001), (median VAS=3 after 6 months, p=0.043). The long-term follow-up revealed less satisfactory result (median VAS=6 after 12 months). High incidence of complications was noted: mainly infection in 3/9 patients. CONCLUSION: Sacral roots stimulation is a non destructive and minimally invasive neuromodulation method in the treatment of chronic pelvic pain. It can be effective even in the long-term observation but special care is advised to secure aseptic conditions in the implantation and to prevent the infection which leads to removal of the stimulating system. PMID- 26377983 TI - Evolution of diagnostic criteria for multiple sclerosis. AB - Multiple sclerosis is a chronic demyelinating disease of the central nervous system that occurs primarily in young adults. There is no single diagnostic test to recognize the disease. The diagnostic criteria, based on clinical examination and laboratory tests, have changed considerably over time. The first guidelines involved only the results of the patient's neurological examination. The diagnostic criteria developed by Poser in 1983 were based largely on the results of additional tests, including visual evoked potentials and analysis of cerebrospinal fluid. The McDonald criteria, developed in 2001 and updated in 2005 and 2010, reflected the diagnostic breakthrough caused by widespread use of magnetic resonance imaging (MRI). Currently, the diagnosis depends largely on the results of the MRI examination. An early diagnosis is particularly important for starting disease-modifying treatments. PMID- 26377984 TI - Potential role of statins in the intracerebral hemorrhage and subarachnoid hemorrhage. AB - Statins are used in primary and secondary prevention of cardiovascular episodes. Most of recent studies regard ischemic stroke. There are more emerging results of studies suggesting usefulness of these drugs in the other types of stroke e.g. intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH). Searching for new methods of treatment is important, because both ICH and SAH lead to poor prognosis and severe psychomotor disability. The unquestionable role of inflammatory factors in the pathogenesis of these disorders justifies considering statin treatment. Previous results are contradictory, thus in present study we review results of studies and try to explain the potential pathomechanism of statin use in hemorrhagic strokes. PMID- 26377985 TI - Neurological presentation of hemophagocytic lymphohistiocytosis. AB - Hemophagocytic lymphohistiocytosis (HLH) is an inflammatory disorder arising from defects in critical regulatory pathways responsible for termination of inflammatory response. We are presenting a case report of a 20-year-old male, admitted to the Department of Neurology because of left lower limb weakness and balance disturbances. After a few days of hospitalization, fever occurred. Laboratory tests revealed anemia, neutropenia, lymphopenia, and thrombocytopenia. The clinical course and laboratory tests results confirmed the diagnosis of HLH. In our opinion, the disorder in the presented case occurred due to severe chronic active Epstein-Barr virus infection syndrome. We are presenting the case of pure neurological onset of hemophagocytic lymphohistiocytosis in an adult patient. Hemophagocytic lymphohistiocytosis, initially presenting with neurological symptoms, can occur in adult patients with irrelevant family history. It is a life-threatening but potentially curable condition requiring proper diagnostic and treatment management. PMID- 26377986 TI - The use of mechanical thrombectomy in the treatment of basilar artery occlusion- case report. AB - Occlusion of the basilar artery (BAO) is a rare cause of stroke, making up approximately 1% of all cases. Ischemic stroke within the basilar artery is associated with serious complications and high mortality (75-91%). BAO may occur initially in the form of mild prodromal symptoms with neurological disorders, the consequences of which can lead to death. For these reasons, BAO requires rapid diagnosis and treatment. We report the case of a 26-year-old man who suffered basilar artery occlusion and was treated with endovascular therapy. The patient was disqualified from intra-venous thrombolysis and endovascular treatment due to exceeding the therapeutic time window. Despite this, due to the location of ischemia and age of the patient, it was decided to proceed with a mechanical thrombectomy (TM). Vessel patency was restored using the Solitaire FR stent. Treatment continued with antiplatelet therapy. Despite a significant overshoot of the time window the procedure was successful and complete recanalization was achieved. During hospitalization, significant neurological symptom reductions were observed. There is no accurate data on which method of treatment of ischemic stroke is best for BAO. Expectations about the effectiveness of endovascular techniques are high. PMID- 26377987 TI - Cowden syndrome and the associated Lhermitte-Duclos disease--Case presentation. AB - We report a patient with features of Cowden syndrome (CS). A 35-year old woman has been suffering from headache, vertigo and mild imbalance since 2 years. Examination showed subtle mucocutaneous lesions: papillomatous papules on the gingival mucosa, a few verrucous acral skin lesions and macrocephaly. Magnetic resonance imaging (MRI) revealed a tumor of the left cerebellar hemisphere with "tiger-striped" pattern on T2-weighted image (T2WI), typical of Lhermitte-Duclos disease (LDD)--one of the pathognomonic but infrequent features of CS. A pathogenic de novo heterozygous PTEN mutation: c.49C>T variant has been identified in exon 1 of the PTEN gene by sequencing. PMID- 26377988 TI - Miller-Fisher syndrome associated with unilateral cerebral white matter lesions. AB - Miller-Fisher syndrome (MFS) is characterized by classical triad of ophthalmoplegia, ataxia and areflexia. The involvement of cerebral white matter in MFS is very rare. We report a typical MFS patient whose brain MRI showed unilateral and extensive involvement in cerebral white matter. We also found mild pleocytosis and raised protein concentration in cerebrospinal fluid. Deficits resolved completely after treatment with intravenous immunoglobulins. Subsequent brain MRI shows cavity formation in involved white matter. PMID- 26377989 TI - Incorporating longitudinal pediatric patient-centered outcome measurement into the clinical workflow using a commercial electronic health record: a step toward increasing value for the patient. AB - Patient-centered outcomes measurement provides healthcare organizations with crucial information for increasing value for patients; however, organizations have struggled to obtain outcomes data from electronic health record (EHR) systems. This study describes how Texas Children's Hospital customized a commercial EHR system and assembled a cross-functional team to capture outcomes data using existing functionality. Prior to its installation and customization, no surgical subspecialties besides the congenital heart and transplant surgery groups conducted prospective, patient outcomes measurement, but by 2015, the outcomes of over 1300 unique patients with supracondylar fractures, cleft lip and/or palate, or voiding dysfunction had been tracked. Key factors for integrating outcomes measurement into the clinical workflow include ongoing communication between cross-functional teams composed of clinicians and technical professionals, an iterative design process, organizational commitment, and prioritizing measurement as early as possible during EHR optimization. PMID- 26377990 TI - Quantifying usability: an evaluation of a diabetes mHealth system on effectiveness, efficiency, and satisfaction metrics with associated user characteristics. AB - OBJECTIVE: Mobile health (mHealth) systems are becoming more common for chronic disease management, but usability studies are still needed on patients' perspectives and mHealth interaction performance. This deficiency is addressed by our quantitative usability study of a mHealth diabetes system evaluating patients' task performance, satisfaction, and the relationship of these measures to user characteristics. MATERIALS AND METHODS: We used metrics in the International Organization for Standardization (ISO) 9241-11 standard. After standardized training, 10 patients performed representative tasks and were assessed on individual task success, errors, efficiency (time on task), satisfaction (System Usability Scale [SUS]) and user characteristics. RESULTS: Tasks of exporting and correcting values proved the most difficult, had the most errors, the lowest task success rates, and consumed the longest times on task. The average SUS satisfaction score was 80.5, indicating good but not excellent system usability. Data trends showed males were more successful in task completion, and younger participants had higher performance scores. Educational level did not influence performance, but a more recent diabetes diagnosis did. Patients with more experience in information technology (IT) also had higher performance rates. DISCUSSION: Difficult task performance indicated areas for redesign. Our methods can assist others in identifying areas in need of improvement. Data about user background and IT skills also showed how user characteristics influence performance and can provide future considerations for targeted mHealth designs. CONCLUSION: Using the ISO 9241-11 usability standard, the SUS instrument for satisfaction and measuring user characteristics provided objective measures of patients' experienced usability. These could serve as an exemplar for standardized, quantitative methods for usability studies on mHealth systems. PMID- 26377991 TI - Use of programme budgeting and marginal analysis as a framework for resource reallocation in respiratory care in North Wales, UK. AB - BACKGROUND: Since the global financial crisis, UK NHS spending has reduced considerably. Respiratory care is a large cost driver for Betsi Cadwaladr University Health Board, the largest health board in Wales. Under the remit of 'prudent healthcare' championed by the Welsh Health Minister, a Programme Budgeting Marginal Analysis (PBMA) of the North Wales respiratory care pathway was conducted. METHODS: A PBMA panel of directors of medicines management, therapies finance, planning, public health and healthcare professionals used electronic voting to establish criteria for decision-making and vote on candidate interventions in which to disinvest and invest. RESULTS: A sum of L86.9 million was spent on respiratory care in 2012-13. Following extensive discussion of 13 proposed candidate interventions facilitated by a chairperson, 4 candidates received recommendations to disinvest, 7 to invest and 2 to maintain current activity. Marginal analysis prioritized mucolytics and high antibiotic prescribing as areas for disinvestment, and medicines waste management and pulmonary rehabilitation for investment. CONCLUSIONS: This exercise demonstrates the potential for health boards to use evidence-based approaches to reach potentially controversial disinvestment and investment decisions. Initial progress has begun with communication from the Medical Director in relation to the disinvestment in mucolytics prescribing and possible redirection of funding options being explored. PMID- 26377993 TI - A Genetic Test for Whether Pairs of Hermaphrodites Can Cross-Fertilize in a Selfing Killifish. AB - Kryptolebias marmoratus, a small killifish that lives in mangrove habitat from southern Florida to Brazil, is one of the planet's only known self-fertilizing hermaphroditic vertebrates. Generation after generation, hermaphroditic individuals simultaneously produce sperm and eggs and internally self-fertilize to produce what are, in effect, highly inbred clones of themselves. Although populations are composed primarily of hermaphrodites, they also contain some true males. The frequency of males in a population varies geographically, from <2% in Florida to as high as 25% in Belize. Males are known to mate occasionally with hermaphrodites, thereby releasing genetic variation that has profound consequences for population genetic structure. However, it is unknown whether hermaphrodites can or do sporadically mate with each other also. Here, we test whether hermaphroditic individuals of the killifish Kryptolebias marmoratus are capable of crossing with one another, in addition to their much more common habits of self-fertilization and occasional outcrossing with pure males. We employ an experimental design in which replicate hermaphrodite pairs were housed together and allowed to reproduce naturally. Among 173 embryos screened at diagnostic microsatellite loci, all were found to result from selfing (i.e., no embryos were the product of a hermaphrodite cross). We thus conclude that hermaphrodite pairs are unlikely to cross, or do so exceedingly rarely. PMID- 26377992 TI - A multiprotein occupancy map of the mRNP on the 3' end of histone mRNAs. AB - The animal replication-dependent (RD) histone mRNAs are coordinately regulated with chromosome replication. The RD-histone mRNAs are the only known cellular mRNAs that are not polyadenylated. Instead, the mature transcripts end in a conserved stem-loop (SL) structure. This SL structure interacts with the stem loop binding protein (SLBP), which is involved in all aspects of RD-histone mRNA metabolism. We used several genomic methods, including high-throughput sequencing of cross-linked immunoprecipitate (HITS-CLIP) to analyze the RNA-binding landscape of SLBP. SLBP was not bound to any RNAs other than histone mRNAs. We performed bioinformatic analyses of the HITS-CLIP data that included (i) clustering genes by sequencing read coverage using CVCA, (ii) mapping the bound RNA fragment termini, and (iii) mapping cross-linking induced mutation sites (CIMS) using CLIP-PyL software. These analyses allowed us to identify specific sites of molecular contact between SLBP and its RD-histone mRNA ligands. We performed in vitro crosslinking assays to refine the CIMS mapping and found that uracils one and three in the loop of the histone mRNA SL preferentially crosslink to SLBP, whereas uracil two in the loop preferentially crosslinks to a separate component, likely the 3'hExo. We also performed a secondary analysis of an iCLIP data set to map UPF1 occupancy across the RD-histone mRNAs and found that UPF1 is bound adjacent to the SLBP-binding site. Multiple proteins likely bind the 3' end of RD-histone mRNAs together with SLBP. PMID- 26377995 TI - Acenocoumarol Pharmacogenetic Dosing Algorithms and Their Application in Two Bulgarian Patients with Low Anticoagulant Requirements. AB - BACKGROUND: The anticoagulant therapy with acenocoumarol is generally associated with a high risk of bleeding and thromboembolic events. PURPOSE: We applied eight already existing acenocoumarol dosing algorithms to Bulgarian patients with low acenocoumarol dose requirements and investigated which of these algorithms would predict most precisely the dose anticoagulant. MATERIALS AND METHODS: Two patients with Bulgarian origin were referred to the outpatient clinical laboratory of "St. Ekaterina" University Hospital for Cardiovascular Surgery and Cardiology, Sofia, Bulgaria. After obtaining written informed consent, both patients were genotyped for polymorphisms in genes for Cytochrome P450 2C9 (CYP2C9), Vitamin K epoxide reductase (VKORC1), Apolipoprotein E (APOE), and Cytochrome P450 4F2 (CYP4F2). RESULTS: All applied acenocoumarol dosing algorithms predicted relatively similar doses of coumarin anticoagulant in both patients. However, van Schie et al.'s algorithm allowed more accurate calculation of the optimal dose in our patients with extremely low acenocoumarol requirements. Genotyping of selected polymorphic variants in CYP2C9 and VKORC1 showed that both patients were compound heterozygotes for CYP2C9 (CYP2C9*2/*3) and homozygotes for both variants in VKORC1 (VKORC1 1173 T/T, and VKORC1-1639 A/A). This combination of genotypes suggested high sensitivity to acenocoumarol leading to the low anticoagulant dose requirements (0.25 and 1 mg/day, respectively) needed to reach the target International Normalized Ratio of 2.5 3.5. CONCLUSIONS: The genotyping of polymorphic variants in VKORC1 and CYP2C9, together with clinical and demographic parameters, can serve for more precise definition of the individual starting and maintenance doses of coumarin derivatives in each patient. PMID- 26377996 TI - Loss of interleukin-21 leads to atrophic germinal centers in multicentric Castleman's disease. AB - Both multicentric Castleman's disease (MCD) and immunoglobulin (Ig)G4-related disease (IgG4-RD) are systemic diseases, presenting with hypergammaglobulinemia and elevated serum levels of IgG4. However, with regard to histopathological findings, MCD shows atrophic germinal centers. On the other hand, expanded germinal centers are detected in IgG4-RD. We extracted germinal centers from specimens of each disorder by microdissection and analyzed the expression of mRNAs by real-time polymerase chain reaction to clarify the mechanisms underlying atrophied germinal centers in MCD. This analysis disclosed loss of interleukin (IL)-21 and B cell lymphoma (Bcl)-6 in the germinal centers of MCD. Loss of IL-21 is considered to be involved in the disappearance of Bcl-6 and leads to atrophied germinal centers in MCD. PMID- 26377997 TI - Economic evaluation in chronic pain: a systematic review and de novo flexible economic model. AB - There is unmet need in patients suffering from chronic pain, yet innovation may be impeded by the difficulty of justifying economic value in a field beset by data limitations and methodological variability. A systematic review was conducted to identify and summarise the key areas of variability and limitations in modelling approaches in the economic evaluation of treatments for chronic pain. The results of the literature review were then used to support the development of a fully flexible open-source economic model structure, designed to test structural and data assumptions and act as a reference for future modelling practice. The key model design themes identified from the systematic review included: time horizon; titration and stabilisation; number of treatment lines; choice/ordering of treatment; and the impact of parameter uncertainty (given reliance on expert opinion). Exploratory analyses using the model to compare a hypothetical novel therapy versus morphine as first-line treatments showed cost effectiveness results to be sensitive to structural and data assumptions. Assumptions about the treatment pathway and choice of time horizon were key model drivers. Our results suggest structural model design and data assumptions may have driven previous cost-effectiveness results and ultimately decisions based on economic value. We therefore conclude that it is vital that future economic models in chronic pain are designed to be fully transparent and hope our open source code is useful in order to aspire to a common approach to modelling pain that includes robust sensitivity analyses to test structural and parameter uncertainty. PMID- 26377999 TI - Single-Nucleotide Polymorphisms and Haplotypes of Intercellular Adhesion Molecule 1 in Uterine Cervical Carcinogenesis in Taiwanese Women. AB - The association of intercellular adhesion molecule 1 (ICAM-1) genetic polymorphisms with uterine cervical carcinogenesis has seldom been reported. Therefore, the aim of this study was to investigate the association of single nucleotide polymorphisms (SNPs) and haplotypes of ICAM-1 with cervical tumorigenesis in Taiwanese women. Four hundred forty four women, including 91 with cervical invasive cancer, 63 with precancerous lesions, and 290 normal controls, were recruited. The genotypic distribution of 4 SNPs of ICAM-1, rs5498 (A1548G), rs5491 (K56M), rs281432 (C8823G), and rs3093030 (C-286T) was determined using real-time polymerase chain reactions and genotyping. Compared to homozygous wild CC, heterozygous CG, homozygous mutant GG, or genotypes with CG/GG display increased risks or a tendency of precancerous lesions or invasive cancer with strong power in rs281432. The homozygotic mutant alleles TT in rs3093030 and homozygotic mutant alleles GG in rs5498 were associated with a higher risk of invasive cancer and precancerous lesions, respectively, but with lower power. The CG/TA/TG haplotypes of ICAM-1 SNPs rs3093030 and rs5498 exhibited a tendency to increase susceptibility to precancerous lesions and invasive cancer. In conclusion, Taiwanese women with ICAM-1 SNP rs281432 and haplotypes CG/TA/TG of rs3093030 and rs5498 are associated with uterine cervical carcinogenesis. PMID- 26378001 TI - Anesthetic substance abuse: international perspectives and parallels. PMID- 26377998 TI - A Cross-Species Analysis of Animal Models for the Investigation of Preterm Birth Mechanisms. AB - BACKGROUND: Spontaneous preterm birth is the leading cause of neonatal morbidity and mortality worldwide. The ability to examine the exact mechanisms underlying this syndrome in humans is limited. Therefore, the study of animal models is critical to unraveling the key physiologic mechanisms that control the timing of birth. The purpose of this review is to facilitate enhanced assimilation of the literature on animal models of preterm birth by a broad range of investigators. METHODS: Using classical systematic and informatics search techniques of the available literature through 2012, a database of intact animal models was generated. Research librarians generated a list of articles using multiple databases. From these articles, a comprehensive list of Medical Subject Headings (MeSH) was created. Using mathematical modeling, significant MeSH descriptors were determined, and a MEDLINE search algorithm was created. The articles were reviewed for mechanism of labor induction categorized by species. RESULTS: Existing animal models of preterm birth comprise specific interventions to induce preterm birth, as no animal model was identified that exhibits natural spontaneous preterm birth at an incidence comparable to that of the humans. A search algorithm was developed which when used results in a comprehensive list of agents used to induce preterm delivery in a host of animal species. The evolution of 3 specific animal models--sheep, mice, and rats--has demonstrated a clear shift in focus in the literature from endocrine to inflammatory agents of preterm birth induction. CONCLUSION: The process of developing a search algorithm to provide efficient access to information on animal models of preterm birth illustrates the need for a more precise organization of the literature to allow the investigator to focus on distinctly maternal versus fetal outcomes. PMID- 26378002 TI - Anesthetic depth and long-term survival: an update. AB - PURPOSE: The purpose of this paper is to review the current evidence relating anesthetic depth to long-term survival after surgery. SOURCE: Using PubMed as the principal source, this review included published studies in all languages comparing mortality in patients with low- and high-processed electro-encephalo graphic index values. PRINCIPAL FINDINGS: All published studies used the bispectral index (BIS) monitor to measure anesthetic depth. The majority of the published observational studies were post hoc analyses of studies undertaken for other purposes. Most of these studies report a statistically significant association between deep general anesthesia (i.e., BIS values < 45) and death. Some studies also suggest an association between deep general anesthesia and myocardial infarction or postoperative cognitive decline. The combination of low BIS values and low delivered anesthetic concentrations (thus defining increased anesthetic sensitivity) may identify patients at particularly high risk. One of the three available randomized controlled trials reports worse outcomes in the BIS = 50 group compared with the BIS > 80 group, and two report no difference in mortality between the BIS = 35 and BIS = 50-55 groups. CONCLUSIONS: The available evidence on anesthetic depth and long-term survival is inconclusive. Randomized controlled trials with carefully controlled arterial blood pressure are required. PMID- 26378003 TI - A Systematic Review of the Effect of Cognitive Strategies on Strength Performance. AB - BACKGROUND: Researchers have tested the beliefs of sportspeople and sports medicine specialists that cognitive strategies influence strength performance. Few investigators have synthesised the literature. OBJECTIVES: The specific objectives were to review evidence regarding (a) the cognitive strategy-strength performance relationship; (b) participant skill level as a moderator; and (c) cognitive, motivational, biomechanical/physiological, and emotional mediators. METHOD: Studies were sourced via electronic databases, reference lists of retrieved articles, and manual searches of relevant journals. Studies had to be randomised or counterbalanced experiments with a control group or condition, repeated measures, and a quality control score above 0.5 (out of 1). Cognitive strategies included goal setting, imagery, self-talk, preparatory arousal, and free choice. Dependent variables included maximal strength, local muscular endurance, or muscular power. RESULTS: Globally, cognitive strategies were reliability associated with increased strength performance (results ranged from 61 to 65 %). Results were mixed when examining the effects of specific strategies on particular dependent variables, although no intervention had an overall negative influence. Indeterminate relationships emerged regarding hypothesised mediators (except cognitive variables) and participant skill level as a moderator. CONCLUSIONS: Although cognitive strategies influence strength performance, there are knowledge gaps regarding specific types of strength, especially muscular power. Cognitive variables, such as concentration, show promise as possible mediators. PMID- 26378005 TI - Medial temporal lobe activity associated with the successful retrieval of destination memory. AB - Destination memory is the process of remembering to whom we tell particular things. Although recent behavioral studies have clarified the cognitive nature of destination memory, the neural mechanisms underlying destination memory retrieval remain unclear. We used functional magnetic resonance imaging (fMRI) to determine whether the medial temporal lobe (MTL), a structure that has been implicated in recollection-based memory, is activated during the successful retrieval of destination information. During a study phase before fMRI scanning, the subjects told a series of facts to either a woman or a man. During fMRI scanning, the subjects were asked to judge whether each fact presented was old or new, and if they judged it as old, to indicate, including a confidence rating (high or low), whether the subjects had told that fact to either a man or a woman. We found that successful destination retrieval, when compared to failed destination retrieval, was associated with increased activity in the parahippocampal gyrus. We also found that the confidence level (high vs. low) for destination memory retrieval was associated with increased activity in another (posterior) region of the parahippocampal gyrus. The present study suggests that the successful retrieval of destination information depends highly on MTL-mediated recollection processes. PMID- 26378004 TI - Use of a robotic device to measure age-related decline in finger proprioception. AB - Age-related changes in proprioception are known to affect postural stability, yet the extent to which such changes affect the finger joints is poorly understood despite the importance of finger proprioception in the control of skilled hand movement. We quantified age-related changes in finger proprioception in 37 healthy young, middle-aged, and older adults using two robot-based tasks wherein participants' index and middle fingers were moved by an exoskeletal robot. The first task assessed finger position sense by asking participants to indicate when their index and middle fingers were directly overlapped during a passive crisscross movement; the second task assessed finger movement detection by asking participants to indicate the onset of passive finger movement. When these tasks were completed without vision, finger position sense errors were 48 % larger in older adults compared to young participants (p < 0.05); proprioceptive reaction time was 78 % longer in older adults compared to young adults (p < 0.01). When visual feedback was provided in addition to proprioception, these age-related differences were no longer apparent. No difference between dominant and non dominant hand performance was found for either proprioception task. These findings demonstrate that finger proprioception is impaired in older adults, and visual feedback can be used to compensate for this deficit. The findings also support the feasibility and utility of the FINGER robot as a sensitive tool for detecting age-related decline in proprioception. PMID- 26378006 TI - Reducing the motor response in haptic parallel matching eliminates the typically observed gender difference. AB - When making two bars haptically parallel to each other, large deviations have been observed, most likely caused by the bias of a hand-centered egocentric reference frame. A consistent finding is that women show significantly larger deviations than men when performing this task. It has been suggested that this difference might be due to the fact that women are more egocentrically oriented than men or are less efficient in overcoming the egocentric bias of the hand. If this is indeed the case, reducing the bias of the egocentric reference frame should eliminate the above-mentioned gender difference. This was investigated in the current study. Sixty participants (30 men, 30 women) were instructed to haptically match (task HP) the orientation of a test bar with the dominant hand to the orientation of a reference bar that was perceived with the non-dominant hand. In a haptic visual task (task HV), in which only the reference bar and exploring hand were out of view, no motor response was required, but participants had to "match" the perceived orientation by verbally naming the parallel orientation that was read out on a test protractor. Both females and males performed better in the HV task than in the HP task. Significant gender effects were only found in the haptic parallelity task (HP), corroborating the idea that women perform at the same level as men when the egocentric bias of the hand is reduced. PMID- 26378007 TI - Interaction effects of visual stimulus speed and contrast on postural sway. AB - Manipulating the characteristics of visual stimuli that simulate self-motion through the environment can affect the resulting postural sway magnitude. In the present study, we address the question whether varying the contrast and speed of a linear translating dot pattern influences medial-lateral postural sway. In a first experiment, we investigated whether the postural sway magnitude increases with increasing dot speed, as was previously demonstrated for expanding and contracting stimuli. In a second experiment, we also manipulated the contrast of the stimuli. For reasons that high-contrast stimuli can be considered 'perceptually' stronger, we expect that higher-contrast stimuli induce more sway than lower-contrast stimuli. The results of the first experiment show that dot speed indeed influences postural sway, although in an unexpected way. For higher speeds, the sway is in the direction of the stimulus motion, yet for lower speeds the sway is in a direction opposite to the stimulus motion. The results of the second experiment show that dot contrast does affect postural sway, but that this depends on the speed of the moving dots. Interestingly, the direction of postural sway induced by a relatively low dot speed (4 degrees /s) depends on dot contrast. Taken together, our results suggest that interactions between the visual, vestibular and proprioceptive system appear to be influenced by an internal representation of the visual stimulus, rather than being influenced by the external visual stimulus characteristics only. PMID- 26378008 TI - Fish Oil and Adjuvant-Induced Arthritis: Inhibitory Effect on Leukocyte Recruitment. AB - Fish oil, a rich source of n-3 fatty acids, has been studied for its beneficial effects in many diseases. Recent studies have shown the robust anti-inflammatory activity of fish oil (FO), when administered orally to rats, in models of acute inflammation. Herein, we investigated if treatment with fish oil preparation (FOP) could interfere with the recruitment of leukocytes into the joint cavity of arthritic rats. We also evaluated the effect of treatment on rolling behavior and leukocyte adhesion in vivo and on leukocyte chemotaxis in vitro. Treatment with FOP (75, 150, and 300 mg/kg) initiated on the day of induction of arthritis (day 0) and maintained for 21 days reduced the total number of leukocytes recruited into the joint cavity, the number of rolling and adhered leukocytes in arthritic rats, and leukocyte migration in response to stimulation with N-formyl-methionyl leucyl-phenylalanine (fMLP) and leukotriene B4 (LTB4). Together, our data provide evidence that FOP plays an important inhibitory role in the recruitment of leukocytes into the joint cavity of arthritic rats. PMID- 26378010 TI - Bioprocess-Technological Potential of Irradiation-Based Fungal Pretreatment Platform Relevant to Lignocellulolytic Biocascade. AB - Lignocellulose-decaying fungal bioplatforms available are not commercially accessible and are limited to short-term use. In this study, those limitations were overcome by developing a platform using water-soaked rice straw (RS) biodegraded by irradiation-based fungal pretreatment (IBFP). This eco-friendly system increased the ability of RS to biodegrade and ferment without the generation of inhibitory compounds. When processed RS (i.e., with a water-soaking ratio of 81 % and irradiation dose of 80 kGy at 1 MeV and 0.12 mA) was pretreated with Dichomitus squalens for 9 days, the sugar yield was 58.5 % of the theoretical maximum. This sugar yield was comparable to that obtained with unirradiated RS for 15 days, which was 57.9 %. Furthermore, the ethanol concentration of 9.7 g L(-1) provided a yield of 58.1 %; the theoretical maximum and productivity at 0.40 g L(-1) h(-1) were determined after simultaneous saccharification and fermentation for 24 h. In addition, microscopic images revealed that IBFP induced predominant ultrastructural modifications to the surface of cell wall fibers. The peroxidative profiles for different biosystems were analyzed in order to understand substrate-specific biocascades based on the differences in biomass components. The activation level of core lignocellulolysis related factors was analogous under the optimized conditions of each system. PMID- 26378011 TI - Simultaneous Bioconversion of Xylose and Glycerol to Xylonic Acid and 1,3 Dihydroxyacetone from the Mixture of Pre-Hydrolysates and Ethanol-Fermented Waste Liquid by Gluconobacter oxydans. AB - Simultaneous bioconversion of xylose and glycerol to xylonic acid and 1,3 dihydroxyacetone (DHA) was realized by using Gluconobacter oxydans (G. oxydans). Currently, the enzymatic hydrolysate to ethanol-fermented waste liquid and the inorganic acid pre-hydrolysate that contain abundant glycerol and xylose were difficult to be utilized or disposed. Based on the method of compressed oxygen supply-sealed and stirred tank reactor system (COS-SSTR), the xylonic acid and 1,3-dihydroxyacetone could be co-produced rapidly with the mixture of the dilute sulfuric acid pre-hydrolysate and ethanol-fermented waste liquid of enzymatic hydrolysate (MPEW) as material. By means of the system, we finally produced 102.3 +/- 3.2 g/L xylonic acid and 40.6 +/- 1.8 g/L 1,3-dihydroxyacetone at yield of 92.4 +/- 2.8 % and 80.6 +/- 3.5 % directly and simultaneously from the mixed solution. The central features of this bioprocess application would enable cost competitive bacterial xylonic acid and 1,3-dihydroxyacetone production from lignocellulosic materials. PMID- 26378009 TI - Ultrastructure and lipid composition of detergent-resistant membranes derived from mammalian sperm and two types of epithelial cells. AB - Lipid rafts are micro-domains of ordered lipids (Lo phase) in biological membranes. The Lo phase of cellular membranes can be isolated from disordered lipids (Ld phase) after treatment with 1 % Triton X-100 at 4 degrees C in which the Lo phase forms the detergent-resistant membrane (DRM) fraction. The lipid composition of DRM derived from Madin-Darby canine kidney (MDCK) cells, McArdle cells and porcine sperm is compared with that of the whole cell. Remarkably, the unsaturation and chain length degree of aliphatic chains attached to phospholipids is virtually the same between DRM and whole cells. Cholesterol and sphingomyelin were enriched in DRMs but to a cell-specific molar ratio. Sulfatides (sphingolipids from MDCK cells) were enriched in the DRM while a seminolipid (an alkylacylglycerolipid from sperm) was depleted from the DRM. Treatment with <5 mM methyl-beta-cyclodextrin (MBCD) caused cholesterol removal from the DRM without affecting the composition and amount of the phospholipid while higher levels disrupted the DRM. The substantial amount of (poly)unsaturated phospholipids in DRMs as well as a low stoichiometric amount of cholesterol suggest that lipid rafts in biological membranes are more fluid and dynamic than previously anticipated. Using negative staining, ultrastructural features of DRM were monitored and in all three cell types the DRMs appeared as multi-lamellar vesicular structures with a similar morphology. The detergent resistance is a result of protein-cholesterol and sphingolipid interactions allowing a relatively passive attraction of phospholipids to maintain the Lo phase. For this special issue, the relevance of our findings is discussed in a sperm physiological context. PMID- 26378012 TI - Methane Production from Rice Straw Hydrolysate Treated with Dilute Acid by Anaerobic Granular Sludge. AB - The traditional anaerobic digestion process of straw to biogas faces bottlenecks of long anaerobic digestion time, low digestion rate, less gas production, etc., while straw hydrolysate has the potential to overcome these drawbacks. In this study, the dilute sulphuric acid-treated hydrolysate of rice straw (DSARSH) containing high sulfate was firstly proved to be a feasible substrate for methane production under mesophilic digestion by granular sludge within a short digestion time. Batch anaerobic digestion process was operated under different initial chemical oxygen demand (COD) values at temperature of 37 degrees C with the pH of 8.5. Among the initial COD values ranging from 3000 to 11,000 mg/L, 5000 mg/L was proved to be the most appropriate considering high COD removal efficiency (94.17 +/- 1.67 %), CH4 content (65.52 +/- 3.12 %), and CH4 yield (0.346 +/- 0.008 LCH4/g COD removed) within 120 h. Furthermore, when the studied system operated at the initial COD of 5000 mg/L, the sulfate removal ratio could reach 56.28 %. PMID- 26378013 TI - In situ immobilized lipase on the surface of intracellular polyhydroxybutyrate granules: preparation, characterization, and its promising use for the synthesis of fatty acid alkyl esters. AB - Photobacterium lipolyticum M37 lipase (LipM37) was immobilized on the surface of intracellular polyhydroxybutyrate (PHB) granules in Escherichia coli. LipM37 was genetically fused to Cupriavidus necator PHA synthase (PhaC Cn ), and the engineered PHB operon containing the lip M37 -phaC Cn successfully mediated the accumulation of PHB granules (85 wt.%) inside E. coli cells. The PHB granules were isolated from the crude cell extract, and the immobilized LipM37 was comparable with the free form of LipM37 except for a favorable increase in thermostability. The immobilized LipM37 was used to synthesize oleic acid methyl ester (biodiesel) and oleic acid dodecyl ester (wax ester), and yielded 98.0 % conversion in esterification of oleic acid and dodecanol. It was suggested that the LipM37-PhaCCn fusion protein successfully exhibited bifunctional activities in E. coli and that in situ immobilization of lipase to the intracellular PHB could be a promising approach for expanding the biocatalytic toolbox for industrial chemical synthesis. PMID- 26378014 TI - Co-expression of Endoxylanase and Endoglucanase in Scheffersomyces stipitis and Its Application in Ethanol Production. AB - Scheffersomyces stipitis strain BCC15191 is considered as a biotechnologically valuable yeast for its ability to ferment glucose and xylose, the main sugar components in plant biomass, to ethanol. However, the wild strain lacks of endogenous cellulases and hemicellulases that limited biomass utilization. In order to improve biomass degrading ability of S. stipitis BCC15191, new integrative plasmids harboring constitutive TEF1 promoter and codon-optimized zeocin or hygromycin antibiotic resistance genes were developed. Aspergillus niger endoxylanase and Aspergillus aculeatus endoglucanase activities were demonstrated in transformant cells expressing codon-optimized genes. S. stipitis co-expressing endoxylanase and endoglucanase was able to grow in medium containing xylan and beta-glucan as carbon sources and directly produced ethanol with yields of 2.7 g/L. It could also use pretreated corncob as a carbon source for ethanol production. These results suggested that recombinant S. stipilis is possible for consolidated bioprocessing of biomass. PMID- 26378015 TI - Exercise capacity and muscle strength and risk of vascular disease and arrhythmia in 1.1 million young Swedish men: cohort study. AB - OBJECTIVE: To investigate the associations of exercise capacity and muscle strength in late adolescence with risk of vascular disease and arrhythmia. DESIGN: Cohort study. SETTING: General population in Sweden. PARTICIPANTS: 1.1 million men who participated in mandatory military conscription between 1 August 1972 and 31 December 1995, at a median age of 18.2 years. Participants were followed until 31 December 2010. MAIN OUTCOMES: Associations between exercise capacity and muscle strength with risk of vascular disease and subgroups (ischaemic heart disease, heart failure, stroke, and cardiovascular death) and risk of arrhythmia and subgroups (atrial fibrillation or flutter, bradyarrhythmia, supraventricular tachycardia, and ventricular arrhythmia or sudden cardiac death). Maximum exercise capacity was estimated by the ergometer bicycle test, and muscle strength was measured as handgrip strength by a hand dynamometer. High exercise capacity or muscle strength was deemed as above the median level. RESULTS: During a median follow-up of 26.3 years, 26 088 vascular disease events and 17 312 arrhythmia events were recorded. Exercise capacity was inversely associated with risk of vascular disease and its subgroups. Muscle strength was also inversely associated with vascular disease risk, driven by associations of higher muscle strength with lower risk of heart failure and cardiovascular death. Exercise capacity had a U shaped association with risk of arrhythmia, driven by a direct association with risk of atrial fibrillation and a U shaped association with bradyarrhythmia. Higher muscle strength was associated with lower risk of arrhythmia (specifically, lower risk of bradyarrhythmia and ventricular arrhythmia). The combination of high exercise capacity and high muscle strength was associated with a hazard ratio of 0.67 (95% confidence interval 0.65 to 0.70) for vascular events and 0.92 (0.88 to 0.97) for arrhythmia compared with the combination of low exercise capacity and low muscle strength. CONCLUSIONS: Exercise capacity and muscle strength in late adolescence are independently and jointly associated with long term risk of vascular disease and arrhythmia. The health benefit of lower risk of vascular events with higher exercise capacity was not outweighed by higher risk of arrhythmia. PMID- 26378016 TI - When Breast Milk Alone Is Not Enough: Barriers to Breastfeeding Continuation among Overweight and Obese Mothers. AB - BACKGROUND: Maternal overweight and obesity are associated with decreased breastfeeding duration. OBJECTIVE: This study aimed to identify barriers to breastfeeding continuation among overweight and obese mothers. METHODS: A retrospective cohort study examining breastfeeding continuation barriers was conducted using results of the Centers for Disease Control and Prevention Pregnancy Risk Assessment Monitoring System survey from Illinois, Maine, and Vermont from 2004 to 2008. SAS Complex Survey version 9.3 was used for analysis. RESULTS: Of 19,145 mothers surveyed, 3717 (19%) were obese and 4367 (23%) were overweight. Overall, 14,731 women initiated breastfeeding, and 6467 discontinued breastfeeding prior to survey completion, around 4 months postpartum. The most common reasons that mothers reported for discontinuing breastfeeding were insufficient milk supply, infant not satisfied with breast milk alone, and breastfeeding difficulty. Overweight and obese women, compared with women of normal weight, had higher odds of discontinuing breastfeeding because their babies were not satisfied by breast milk alone (overweight: odds ratio [OR] = 1.39, 95% confidence interval [CI], 1.16-1.68; obese: OR = 1.26, 95% CI, 1.03 1.54). Obese mothers, compared with normal weight mothers, had lower odds of discontinuing breastfeeding because it felt like the right time (OR = 0.64, 95% CI, 0.47-0.88) and higher odds of discontinuing due to breastfeeding difficulties (OR = 1.29, 95% CI, 1.05-1.58) and infant jaundice (OR = 1.81, 95% CI, 1.26 2.60). CONCLUSION: Obese and overweight mothers were significantly more likely to discontinue breastfeeding due to infant dissatisfaction with breast milk alone. Obese mothers had higher odds than normal weight mothers of discontinuing breastfeeding due to breastfeeding difficulties and infant jaundice. Breastfeeding education and support should be enhanced for this at-risk population. PMID- 26378017 TI - High PD-L1 expression was associated with poor prognosis in 870 Chinese patients with breast cancer. AB - BACKGROUND: To investigate the role of PD-L1 expression in tumor recurrence and metastasis in Chinese patients with breast cancer. METHODS: Suitable tissue samples were available from 870 patients with breast cancer. Paraffin-embedded tumor sections were stained with PD-L1 antibody. The correlations between PD-L1 expression and clinical characteristics, ER/PR/HER2 status and survival parameters were analyzed. Kaplan-Meier and univariate Cox proportional hazards model analyses were used to compare the survival of patients with high PD-L1 expression and patients with no PD-L1 expression. RESULTS: The median follow-up time was 98 months(range, 17-265 months).The positive rate of PD-L1 expression in breast cancer was 21.7% (189/870). PD-L1 high expression was inversely associated with larger tumor size, higher tumor grade, more positive lymph node number, as well as negative ER and PR status. PD-L1 expression was particularly higher in TNBC compared with non-TNBC, although no statistical significance was observed. Nomogram logistic regression results based on clinical and pathological features showed that the following factors were more likely associated with high PD-L1 expression: patient age younger than 35 years, larger tumor size, lymphovascular invasion and advanced stage. Our data indicated that patients with high PD-L1 expression had poor DFS, DMFS and overall survival compared with those with no PD L1 expression. Univariate Cox proportional hazards model analysis showed that PD L1 was an independent prognostic factor for tumor prognosis. CONCLUSIONS: PD-L1 expression is an important indicator of unfavorable prognosis in breast cancer patients. PMID- 26378018 TI - Differential regulation of metabolic pathways by androgen receptor (AR) and its constitutively active splice variant, AR-V7, in prostate cancer cells. AB - Metastatic prostate cancer (PCa) is primarily an androgen-dependent disease, which is treated with androgen deprivation therapy (ADT). Tumors usually develop resistance (castration-resistant PCa [CRPC]), but remain androgen receptor (AR) dependent. Numerous mechanisms for AR-dependent resistance have been identified including expression of constitutively active AR splice variants lacking the hormone-binding domain. Recent clinical studies show that expression of the best characterized AR variant, AR-V7, correlates with resistance to ADT and poor outcome. Whether AR-V7 is simply a constitutively active substitute for AR or has novel gene targets that cause unique downstream changes is unresolved. Several studies have shown that AR activation alters cell metabolism. Using LNCaP cells with inducible expression of AR-V7 as a model system, we found that AR-V7 stimulated growth, migration, and glycolysis measured by ECAR (extracellular acidification rate) similar to AR. However, further analyses using metabolomics and metabolic flux assays revealed several differences. Whereas AR increased citrate levels, AR-V7 reduced citrate mirroring metabolic shifts observed in CRPC patients. Flux analyses indicate that the low citrate is a result of enhanced utilization rather than a failure to synthesize citrate. Moreover, flux assays suggested that compared to AR, AR-V7 exhibits increased dependence on glutaminolysis and reductive carboxylation to produce some of the TCA (tricarboxylic acid cycle) metabolites. These findings suggest that these unique actions represent potential therapeutic targets. PMID- 26378019 TI - Cranberry proanthocyanidins inhibit esophageal adenocarcinoma in vitro and in vivo through pleiotropic cell death induction and PI3K/AKT/mTOR inactivation. AB - Cranberries are rich in bioactive constituents known to improve urinary tract health and more recent evidence supports cranberries possess cancer inhibitory properties. However, mechanisms of cancer inhibition by cranberries remain to be elucidated, particularly in vivo. Properties of a purified cranberry-derived proanthocyanidin extract (C-PAC) were investigated utilizing acid-sensitive and acid-resistant human esophageal adenocarcinoma (EAC) cell lines and esophageal tumor xenografts in athymic NU/NU mice. C-PAC induced caspase-independent cell death mainly via autophagy and low levels of apoptosis in acid-sensitive JHAD1 and OE33 cells, but resulted in cellular necrosis in acid-resistant OE19 cells. Similarly, C-PAC induced necrosis in JHAD1 cells pushed to acid-resistance via repeated exposures to an acidified bile cocktail. C-PAC associated cell death involved PI3K/AKT/mTOR inactivation, pro-apoptotic protein induction (BAX, BAK1, deamidated BCL-xL, Cytochrome C, PARP), modulation of MAPKs (P-P38/P-JNK) and G2 M cell cycle arrest in vitro. Importantly, oral delivery of C-PAC significantly inhibited OE19 tumor xenograft growth via modulation of AKT/mTOR/MAPK signaling and induction of the autophagic form of LC3B supporting in vivo efficacy against EAC for the first time. C-PAC is a potent inducer of EAC cell death and is efficacious in vivo at non-toxic behaviorally achievable concentrations, holding promise for preventive or therapeutic interventions in cohorts at increased risk for EAC, a rapidly rising and extremely deadly malignancy. PMID- 26378020 TI - Expression profile of innate immune receptors, NLRs and AIM2, in human colorectal cancer: correlation with cancer stages and inflammasome components. AB - NLRs (nucleotide-binding domain leucine-rich repeat proteins or NOD-like receptors) are regulators of inflammation and immunity. A subgroup of NLRs and the innate immune receptor, AIM2 (absent-in-melanoma 2), can induce the assembly of a large caspase-1 activating complex called the inflammasome. Other NLRs regulate key signaling pathways such as NF-kB and MAPK. Since inflammation is a central component of colorectal cancer (CRC), this work was undertaken to analyze NLR and AIM2 expression in human CRC by combining bioinformatics analysis and experimental verification using clinical tissue samples. Additional experiments analyzed the association of (i) gene expression and cancer staging, and (ii) gene expression among inflammasome components.Ten public CRC datasets from the Oncomine(r) Platform were analyzed. Genes analyzed include NLRP1, NLRP3, NLRP6, NLRP12, NLRC3, NLRC4, NLRC5, NOD1, NOD2 and AIM2. Additionally, forty case matched cancer samples and adjacent healthy control tissues isolated from a cohort of Chinese CRC patients were profiled.Three patterns of gene expression in CRC are shown. The expression of NLRC3, a checkpoint of inflammation, and the inflammasome components NLRP1, NLRP3, NLRC4 and AIM2 were reduced in CRC. NOD1 and NOD2 expression was increased in CRC, while NLRC5, NLRP6 and NLRP12 showed little difference compared to controls. Reduced expression of NLRC3 in CRC was verified in all available databases analyzed and confirmed with our patient cohort. Furthermore, the extent of NLRC3 and AIM2 gene reduction was correlated with cancer progression. This report reveals the potential value of NLR and AIM2 genes as biomarkers of CRC and cancer progression. PMID- 26378021 TI - CD19+CD24hiCD38hiBregs involved in downregulate helper T cells and upregulate regulatory T cells in gastric cancer. AB - Regulatory B cells (Bregs) play a critical role in inflammation and autoimmune disease. We characterized the role of Bregs in the progression of gastric cancer. We detected an increase in Bregs producing IL-10 both in peripheral blood mononuclear cells (PBMCs) and in gastric tumors. Multicolor flow cytometry analysis revealed that a subset of CD19+CD24hiCD38hi B cells produces IL-10. Functional studies indicated that increased Bregs do not inhibit the proliferation of CD3+T cells or CD4+ helper T cells (Th cells). However, Bregs do suppress the secretion of IFN-gamma and TNF-alpha by CD4+Th cells. CD19+CD24hiCD38hiBregs were also found to correlate positively with CD4+FoxP3+ regulatory T cells (Tregs). Neutralization experiments showed that Bregs convert CD4+CD25- effector T cells to CD4+FoxP3+Tregs via TGF-beta1. Collectively, these findings demonstrate that increased Bregs play a immunosuppressive role in gastric cancer by inhibiting T cells cytokines as well as conversion to Tregs. These results may provide new clues about the underlying mechanisms of immune escape in gastric cancer. PMID- 26378022 TI - Golgi protein 73 activation of MMP-13 promotes hepatocellular carcinoma cell invasion. AB - Golgi Protein 73 (GP73) is a serum biomarker for hepatocellular carcinoma (HCC), however its role in HCC is not clear. We report that GP73 promotes cell invasion, the hallmark of malignancy, through the upregulation of matrix metalloproteinase 13 (MMP-13). GP73 enhances MMP-13 expression through cAMP responsive element binding protein (CREB)-mediated transcription activation. Levels of GP73 and MMP 13 are increased and positively correlated in human HCC tissues. Augmented MMP-13 potentiates HCC cell metastasis. Thus, the GP73-CREB-MMP-13 axis potentiates cancer cell invasion and may be a target for HCC treatment. PMID- 26378023 TI - The NF-kappaB p65/miR-23a-27a-24 cluster is a target for leukemia treatment. AB - p65 is a transcription factor that is involved in many physiological and pathologic processes. Here we report that p65 strongly binds to the miR-23a-27a 24 cluster promoter to up-regulate its expression. As bone marrow-derived cells differentiate into red blood cells in vitro, p65/miR-23a-27a-24 cluster expression increases sharply and then declines before the appearance of red blood cells, suggesting that this cluster is negatively related to erythroid terminal differentiation. Bioinformatic and molecular biology experiments confirmed that the miR-23a-27a-24 cluster inhibited the expression of the erythroid proteome and contributed to erythroleukemia progression. In addition, high level of the p65/miR-23a-27a-24 cluster was found in APL and AML cell lines and in nucleated peripheral blood cells from leukemia patients. Furthermore, anti-leukemia drugs significantly inhibited the expression of the p65/miR-23a-27a-24 cluster in leukemia cells. Administration of the p65 inhibitor parthenolide significantly improved hematology and myelogram indices while prolonging the life span of erythroleukemia mice. Meanwhile, stable overexpression of these three miRNAs in mouse erythroleukemia cells enhanced cell malignancy. Our findings thus connect a novel regulation pathway of the p65/miR-23a-27a-24 cluster with the erythroid proteome and provide an applicable approach for treating leukemia. PMID- 26378025 TI - Onychomycosis Associated with Exophiala oligosperma in Taiwan. AB - A fungus was isolated from a nail of a 54-year-old female patient with onychomycosis in Taiwan. Based on ITS rDNA as well as beta tubulin gene sequences and microscopic analyses, this fungus was identified as Exophiala oligosperma. This is the first record of E. oligosperma in Taiwan. Negative keratin azure test indicates that keratin degradation is not involved in cases of E. oligosperma associated with skin and nail diseases. PMID- 26378024 TI - Prostaglandin E receptor 4 (EP4) promotes colonic tumorigenesis. AB - Colorectal cancer (CRC) continues to be a major cause of morbidity and mortality. Although the factors underlying CRC development and progression are multifactorial, there is an important role for tumor-host interactions, especially interactions with myeloid cells. There is also increasing evidence that cyclooxygenase-derived prostaglandins are important mediators of CRC development and growth. Although prevention trials with either nonselective NSAIDs or COX-2 selective agents have shown promise, the gastrointestinal or cardiovascular side effects of these agents have limited their implementation. The predominant prostaglandin involved in CRC pathogenesis is PGE2. Since myeloid cells express high levels of the PGE2 receptor subtype, EP4, we selectively ablated EP4 in myeloid cells and studied adenoma formation in a mouse model of intestinal adenomatous polyposis, ApcMin/+ mice. ApcMin/+mice with selective myeloid cell deletion of EP4 had marked inhibition of both adenoma number and size, with associated decreases in mTOR and ERK activation. Either genetic or pharmacologic inhibition of EP4 receptors led to an anti-tumorigenic M1 phenotype of macrophages/dendritic cells. Therefore, PGE2-mediated EP4 signaling in myeloid cells promotes tumorigenesis, suggesting EP4 as a potentially attractive target for CRC chemoprevention or treatment. PMID- 26378026 TI - Uninsurance Disparities Have Narrowed For Black And Hispanic Adults Under The Affordable Care Act. PMID- 26378027 TI - Proinflammatory mesenchymal effects of the non-genotoxic hepatocarcinogen phenobarbital: a novel mechanism of antiapoptosis and tumor promotion. AB - Many environmental pollutants and drugs, including steroid hormones, hypolipidemics and antiepileptics, are non-genotoxic carcinogens (NGC) in rodent liver. The mechanism of action and the risk for human health are still insufficiently known. Here, we study the effects of phenobarbital (PB), a widely used model NGC, on hepatic epithelial-mesenchymal crosstalk and the impact on hepatic apoptosis. Mesenchymal cells (MC) and hepatocytes (HC) were isolated from control and PB-treated rat livers. PB induced extensive changes in gene expression in MC and much less in HC as shown by transcriptomics with oligoarrays. In MC only, transcript levels of numerous proinflammatory cytokines were elevated. Correspondingly, ELISA on the supernatant of MC from PB-treated rats revealed enhanced release of various cytokines. In cultured HC, this supernatant caused (i) nuclear translocation and activation of nuclear factor kappaB (shown by immunoblots of nuclear extracts and reporter gene assays), (ii) elevated expression of proinflammatory genes and (iii) protection from the proapoptotic action of transforming growth factor beta 1 (TGFbeta1). PB treatment in vivo or in vitro elevated the production and release of tumor necrosis factor alpha from MC, which was identified as mainly responsible for the inhibition of apoptosis in HC. In conclusion, our findings reveal profound proinflammatory effects of PB on hepatic mesenchyme and mesenchymal-epithelial interactions. The resulting release of cytokines acts antiapoptotic in HC, an effect crucial for tumor promotion and carcinogenesis by NGC. PMID- 26378028 TI - Brain iron deposits and lifespan cognitive ability. AB - Several studies have reported associations between brain iron deposits and cognitive status, and cardiovascular and neurodegenerative diseases in older individuals, but the mechanisms underlying these associations remain unclear. We explored the associations between regional brain iron deposits and different factors of cognitive ability (fluid intelligence, speed and memory) in a large sample (n = 662) of individuals with a mean age of 73 years. Brain iron deposits in the corpus striatum were extracted automatically. Iron deposits in other parts of the brain (i.e., white matter, thalamus, brainstem and cortex), brain tissue volume and white matter hyperintensities (WMH) were assessed separately and semi automatically. Overall, 72.8 % of the sample had iron deposits. The total volume of iron deposits had a small but significant negative association with all three cognitive ability factors in later life (mean r = -0.165), but no relation to intelligence in childhood (r = 0.043, p = 0.282). Regression models showed that these iron deposit associations were still present after control for a variety of vascular health factors, and were separable from the association of WMH with cognitive ability. Iron deposits were also associated with cognition across the lifespan, indicating that they are relevant for cognitive ability only at older ages. Iron deposits might be an indicator of small vessel disease that affects the neuronal networks underlying higher cognitive functioning. PMID- 26378029 TI - Cone-beam computed tomography in pediatric dentistry, a retrospective observational study. AB - OBJECTIVES: The aim of this study was to find the reasons for referral and their correlation with age, gender, field of view, and resolution for all patients under the age of 18 who underwent a cone-beam computed tomography (CBCT) scan between 1 May 2010 and 1 May 2012 in the dental out-patient clinic of the University Hospital Ghent. MATERIAL AND METHODS: From the local CBCT database, 79 pediatric patients gave their consent. Subsequently age, gender, reason for referral, external or internal referral, field of view (FOV), and resolution data were collected. Descriptive and comparative statistical analysis was performed. RESULTS: There seemed to be a correlation between orthodontic referrals and female patients. The majority of patients referred for trauma follow-up were 12 years and older. Fourteen percent of referrals were for dento-alveolar trauma, 18 % for other dento-alveolar reasons, 4 % for developing dentition-generalized, 36 % for developing dentition-localized, 10 % for endodontics, 1 % for periodontics, 16 % for surgical applications, and 1 % was for the visualization of the TMJ. Eighty percent of the CBCTs were taken at a FOV 50 * 55 mm. Larger FOV was used for surgical planning or follow-up reasons. The majority of the CBCTs was taken at a resolution of 200 MUm, while a resolution of 150 MUm was used for endodontic issues. From these results, a classification system for referral was developed. CONCLUSIONS: From the present study, it can be concluded that a referral pattern could be detected which was correlated with gender, age group, FOV, and resolution. These results can help practitioners make the decision to refer for CBCT when extra three dimensional imaging is expected to have a benefit in therapeutic value for a pediatric or adolescent patient. CLINICAL RELEVANCE: This study can guide dental professionals referring pediatric and adolescent patients for CBCT. PMID- 26378030 TI - Efficacy of the FIFA 11+ Injury Prevention Program in the Collegiate Male Soccer Player. AB - BACKGROUND: The Federation Internationale de Football Association (FIFA) 11+ program has been shown to be an effective injury prevention program in the female soccer cohort, but there is a paucity of research to demonstrate its efficacy in the male population. HYPOTHESIS: To examine the efficacy of the FIFA 11+ program in men's collegiate United States National Collegiate Athletic Association (NCAA) Division I and Division II soccer. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: Before the commencement of the fall 2012 season, every NCAA Division I and Division II men's collegiate soccer team (N = 396) was solicited to participate in this research study. Human ethics review board approval was obtained through Quorum Review IRB. Sixty-five teams were randomized: 34 to the control group (CG; 850 players) and 31 to the intervention group (IG; 675 players). Four teams in the IG did not complete the study, reducing the number for analysis to 61. The FIFA 11+ injury prevention program served as the intervention and was utilized weekly. Athlete-exposures (AEs), compliance, and injury data were recorded using a secure Internet-based system. RESULTS: In the CG, 665 injuries (mean +/- SD, 19.56 +/- 11.01) were reported for 34 teams, which corresponded to an incidence rate (IR) of 15.04 injuries per 1000 AEs. In the IG, 285 injuries (mean +/- SD, 10.56 +/- 3.64) were reported for 27 teams, which corresponded to an IR of 8.09 injuries per 1000 AEs. Total days missed because of injury were significantly higher for the CG (mean +/- SD, 13.20 +/- 26.6 days) than for the IG (mean +/- SD, 10.08 +/- 14.68 days) (P = .007). There was no difference for time loss due to injury based on field type (P = .341). CONCLUSION: The FIFA 11+ significantly reduced injury rates by 46.1% and decreased time loss to injury by 28.6% in the competitive male collegiate soccer player (rate ratio, 0.54 [95% CI, 0.49-0.59]; P < .0001) (number needed to treat = 2.64). PMID- 26378031 TI - Epidemiology of Exercise- and Sports-Related Injuries in a Population of Young, Physically Active Adults: A Survey of Military Servicemembers. AB - BACKGROUND: Numerous studies document the health benefits of a physically active lifestyle, but relatively few document the hazards of physical activity. Because of the requirement for physical fitness to complete their mission, the United States military services have a vested interest in understanding the benefits and risks of physical activity including exercise and sports. One of these risks is injury. Rates and proportion of injuries caused by exercise- and sports-related (ESR) activities have not been reported previously across the services. PURPOSE: The purposes of this population survey were to (1) document the rates and proportion of all injuries caused by ESR activities among military personnel, (2) compare rates across the military services, and (3) describe the causes and types of ESR injuries as well as associated days of limited activity. STUDY DESIGN: Descriptive epidemiology study. METHODS: The Defense Manpower Data Center administered the web-based 2008 Status of Forces Survey of Active Duty Service Members to a random sample of active-duty personnel. In all, 10,692 servicemembers completed the survey, which included questions about injuries from any cause and from exercise and sports during the previous year. Responses were weighted to produce population estimates for injury rates (any injury and ESR injury). Percentage distributions were used to describe activities, injury types, days of limited activity, and contributing factors for ESR injuries. RESULTS: There were 49% of servicemembers who sustained an injury from any cause in the previous year; 25% had an ESR injury. Thus, 52% of all injuries were ESR injuries. ESR injury rates ranged from 20% for the Navy to 33% for the Marine Corps. Running accounted for 45% of ESR injuries. Forty percent of ESR injuries were sprains and strains. As an indicator of injury severity, 35% of ESR injuries required more than 2 weeks of limited activity. CONCLUSION: This study quantified the overall incidence of injuries and the large proportion that are caused by exercise and sports among military personnel, a population of healthy, physically active adults. Prevention strategies should focus on running, weight training, basketball, and football. Recommendations include adherence to evidence-based practices to reduce the occurrence of ESR injuries. PMID- 26378032 TI - Bleeding caecal mass: a rare finding. AB - Bleeding from a caecal mass is a common clinical scenario encountered in surgical practice. Tumours, diverticulitis, inflammation and vascular malformations are the most common causes of this bleeding. We present a case of a submucosal bleeding caecal mass, which turned out to be an appendiceal faecolith protruding into the caecum. Although we found one reported case of this previously, it was not encountered in the emergency setting. PMID- 26378034 TI - Releasing the Brake on Oncolytic Viral Therapy. AB - Oncolytic virus that selectively targets and eradicates tumor cells and immune checkpoint blockade that unleashes host antitumor immune responses show synergistic effects against cancer. This combination holds great promise for future treatment of a broad range of cancers in patients. Clin Cancer Res; 21(24); 5417-9. (c)2015 AACR.See related article by Rojas et al., p. 5543. PMID- 26378033 TI - A Randomized Phase II Crossover Study of Imatinib or Rituximab for Cutaneous Sclerosis after Hematopoietic Cell Transplantation. AB - PURPOSE: Cutaneous sclerosis occurs in 20% of patients with chronic graft-versus host disease (GVHD) and can compromise mobility and quality of life. EXPERIMENTAL DESIGN: We conducted a prospective, multicenter, randomized, two-arm phase II crossover trial of imatinib (200 mg daily) or rituximab (375 mg/m(2) i.v. weekly * 4 doses, repeatable after 3 months) for treatment of cutaneous sclerosis diagnosed within 18 months (NCT01309997). The primary endpoint was significant clinical response (SCR) at 6 months, defined as quantitative improvement in skin sclerosis or joint range of motion. Treatment success was defined as SCR at 6 months without crossover, recurrent malignancy or death. Secondary endpoints included changes of B-cell profiles in blood (BAFF levels and cellular subsets), patient-reported outcomes, and histopathology between responders and nonresponders with each therapy. RESULTS: SCR was observed in 9 of 35 [26%; 95% confidence interval (CI); 13%-43%] participants randomized to imatinib and 10 of 37 (27%; 95% CI, 14%-44%) randomized to rituximab. Six (17%; 95% CI, 7%-34%) patients in the imatinib arm and 5 (14%; 95% CI, 5%-29%) in the rituximab arm had treatment success. Higher percentages of activated B cells (CD27(+)) were seen at enrollment in rituximab-treated patients who had treatment success (P = 0.01), but not in imatinib-treated patients. CONCLUSIONS: These results support the need for more effective therapies for cutaneous sclerosis and suggest that activated B cells define a subgroup of patients with cutaneous sclerosis who are more likely to respond to rituximab. PMID- 26378035 TI - Using Whole-Exome Sequencing to Identify Genetic Markers for Carboplatin and Gemcitabine-Induced Toxicities. AB - PURPOSE: Chemotherapies are associated with significant interindividual variability in therapeutic effect and adverse drug reactions. In lung cancer, the use of gemcitabine and carboplatin induces grade 3 or 4 myelosuppression in about a quarter of the patients, while an equal fraction of patients is basically unaffected in terms of myelosuppressive side effects. We therefore set out to identify genetic markers for gemcitabine/carboplatin-induced myelosuppression. EXPERIMENTAL DESIGN: We exome sequenced 32 patients that suffered extremely high neutropenia and thrombocytopenia (grade 3 or 4 after first chemotherapy cycle) or were virtually unaffected (grade 0 or 1). The genetic differences/polymorphism between the groups were compared using six different bioinformatics strategies: (i) whole-exome nonsynonymous single-nucleotide variants association analysis, (ii) deviation from Hardy-Weinberg equilibrium, (iii) analysis of genes selected by a priori biologic knowledge, (iv) analysis of genes selected from gene expression meta-analysis of toxicity datasets, (v) Ingenuity Pathway Analysis, and (vi) FunCoup network enrichment analysis. RESULTS: A total of 53 genetic variants that differed among these groups were validated in an additional 291 patients and were correlated to the patients' myelosuppression. In the validation, we identified rs1453542 in OR4D6 (P = 0.0008; OR, 5.2; 95% CI, 1.8 18) as a marker for gemcitabine/carboplatin-induced neutropenia and rs5925720 in DDX53 (P = 0.0015; OR, 0.36; 95% CI, 0.17-0.71) as a marker for thrombocytopenia. Patients homozygous for the minor allele of rs1453542 had a higher risk of neutropenia, and for rs5925720 the minor allele was associated with a lower risk for thrombocytopenia. CONCLUSIONS: We have identified two new genetic markers with the potential to predict myelosuppression induced by gemcitabine/carboplatin chemotherapy. PMID- 26378036 TI - Human mesenchymal stem cells enhance the systemic effects of radiotherapy. AB - The outcome of radiotherapy treatment might be further improved by a better understanding of individual variations in tumor radiosensitivity and normal tissue reactions, including the bystander effect. For many tumors, however, a definitive cure cannot be achieved, despite the availablity of more and more effective cancer treatments. Therefore, any improvement in the efficacy of radiotherapy will undoubtedly benefit a significant number of patients. Many experimental studies measure a bystander component of tumor cell death after radiotherapy, which highlights the importance of confirming these observations in a preclinical situation. Mesenchymal stem cells (MSCs) have been investigated for use in the treatment of cancers as they are able to both preferentially home onto tumors and become incorporated into their stroma. This process increases after radiation therapy. In our study we show that in vitro MSCs, when activated with a low dose of radiation, are a source of anti-tumor cytokines that decrease the proliferative activity of tumor cells, producing a potent cytotoxic synergistic effect on tumor cells. In vivo administration of unirradiated mesenchymal cells together with radiation leads to an increased efficacy of radiotherapy, thus leading to an enhancement of short and long range bystander effects on primary irradiated tumors and distant-non-irradiated tumors. Our experiments indicate an increased cell loss rate and the decrease in the tumor cell proliferation activity as the major mechanisms underlying the delayed tumor growth and are a strong indicator of the synergistic effect between RT and MSC when they are applied together for tumor treatment in this model. PMID- 26378037 TI - Intracellular activation of EGFR by fatty acid synthase dependent palmitoylation. AB - Epidermal growth factor receptor (EGFR) is an oncogenic receptor tyrosine kinase. Canonically, the tyrosine kinase activity of EGFR is regulated by its extracellular ligands. However, ligand-independent activation of EGFR exists in certain cancer cells, and the underlying mechanism remains to be defined. In this study, using PC3 and A549 cells as a model, we have found that, in the absence of extracellular ligands, a subpopulation of EGFR is constitutively active, which is needed for maintaining cell proliferation. Furthermore, we have found that fatty acid synthase (FASN)-dependent palmitoylation of EGFR is required for EGFR dimerization and kinase activation. Inhibition of FASN or palmitoyl acyltransferases reduced the activity and down-regulated the levels of EGFR, and sensitized cancer cells to EGFR tyrosine kinase inhibitors. It is concluded that EGFR can be activated intracellularly by FASN-dependent palmitoylation. This mechanism may serve as a new target for improving EGFR-based cancer therapy. PMID- 26378038 TI - Induction of USP17 by combining BET and HDAC inhibitors in breast cancer cells. AB - Members of the bromodomain and extra-C terminal (BET) domain protein family and the histone deacetylase (HDAC) enzyme family regulate the expression of important oncogenes and tumor suppressor genes. Here we show that the BET inhibitor JQ1 inhibits proliferation and induces apoptosis of both triple negative and estrogen receptor positive breast cancer cells. Consistent with the critical role of histone acetylation in the regulation of gene expression, treatment with JQ1 or the HDAC inhibitor mocetinostat was associated with global changes in gene expression resulting in suppression of genes involved in cell-cycle regulation. Combining JQ1 with mocetinostat, further decreased cell viability. This synergistic effect was associated with increased suppression of genes essential for cell-cycle progression. Furthermore, we detected dramatic increase in the expression of several members of the ubiquitin-specific protease 17 (USP17) family of deubiquitinating enzymes in response to the combination treatment. Increased expression of USP17 enzymes were able to attenuate the Ras/MAPK pathway causing decrease in cell viability, while, siRNA mediated depletion of USP17 significantly decreased cytotoxicity after the combination treatment. In conclusion, our study demonstrates that co-treatment with BET inhibitors and HDAC inhibitors reduces breast cancer cell viability through induction of USP17. PMID- 26378039 TI - SIP1 is a downstream effector of GADD45G in senescence induction and growth inhibition of liver tumor cells. AB - Cellular senescence evasion caused by the inactivation of tumor suppressive programs is implicated in tumor initiation and therapeutic resistance. Our previous study has shown that the downregulation of growth arrest and DNA damage 45G (GADD45G) contributes to senescence bypass in hepatocellular carcinoma (HCC). Here, we report that the Smad-interacting protein-1 (SIP1) is transcriptionally activated and functions critically in the GADD45G-induced tumor cell senescence. Knockdown of SIP1 significantly abrogates the suppressive effects of GADD45G on the growth of xenografted liver tumor in vivo. The essential role of SIP1 in GADD45G activities is further validated in the model of the proteasome inhibitor MG132-induced cell senescence. We further show that JNK but not p38 MAPK activation is involved in the GADD45G-mediated SIP1 upregulation, and that JNK inhibition counteracts the GADD45G-induced cellular senescence. More importantly, we show that GADD45G and SIP1 expression are coincidently downregulated in primary human HCC tissues. Together, our results establish that the dowregulation of GADD45G-SIP1 axis may contribute to cellular senescence evasion and HCC development. PMID- 26378040 TI - GRP78 confers the resistance to 5-FU by activating the c-Src/LSF/TS axis in hepatocellular carcinoma. AB - 5-FU is a common first-line chemotherapeutic drug for the treatment of hepatocellular carcinoma. However the development of acquired resistance to 5-FU confines its clinical usages. Although this phenomenon has been the subject of intense investigation, the exact mechanism of acquired resistance to 5-FU remains elusive. Here, we report that over-expression of GRP78 contributes to acquired resistance to 5-FU in HCC by up-regulating the c-Src/LSF/TS axis. Moreover, we found that the resistance to 5-FU conferred by GRP78 is mediated by its ATPase domain. The ATPase domain differentially increased the expression of LSF, TS and promoted the phosphorylation of ERK and Akt. We further identified that GRP78 interacts physically with c-Src through its ATPase domain and promotes the phosphorylation of c-Src, which in turn increases the expression of LSF in the nucleus. Together, GRP78 confers the resistance to 5-FU by up-regulating the c Src/LSF/TS axis via its ATPase domain. PMID- 26378041 TI - Differential susceptibility to colorectal cancer due to naturally occurring gut microbiota. AB - Recent studies investigating the human microbiome have identified particular bacterial species that correlate with the presence of colorectal cancer. To evaluate the role of qualitatively different but naturally occurring gut microbiota and the relationship with colorectal cancer development, genetically identical embryos from the Polyposis in Rat Colon (Pirc) rat model of colorectal cancer were transferred into recipients of three different genetic backgrounds (F344/NHsd, LEW/SsNHsd, and Crl:SD). Tumor development in the pups was tracked longitudinally via colonoscopy, and end-stage tumor burden was determined. To confirm vertical transmission and identify associations between the gut microbiota and disease phenotype, the fecal microbiota was characterized in recipient dams 24 hours pre-partum, and in Pirc rat offspring prior to and during disease progression. Our data show that the gut microbiota varies between rat strains, with LEW/SsNHsd having a greater relative abundance of the bacteria Prevotella copri. The mature gut microbiota of pups resembled the profile of their dams, indicating that the dam is the primary determinant of the developing microbiota. Both male and female F344-Pirc rats harboring the Lewis microbiota had decreased tumor burden relative to genetically identical rats harboring F344 or SD microbiota. Significant negative correlations were detected between tumor burden and the relative abundance of specific taxa from samples taken at weaning and shortly thereafter, prior to observable adenoma development. Notably, this naturally occurring variation in the gut microbiota is associated with a significant difference in severity of colorectal cancer, and the abundance of certain taxa is associated with decreased tumor burden. PMID- 26378042 TI - HSulf-1 deficiency dictates a metabolic reprograming of glycolysis and TCA cycle in ovarian cancer. AB - Warburg effect has emerged as a potential hallmark of many cancers. However, the molecular mechanisms that led to this metabolic state of aerobic glycolysis, particularly in ovarian cancer (OVCA) have not been completely elucidated. HSulf 1 predominantly functions by limiting the bioavailability of heparan binding growth factors and hence their downstream signaling. Here we report that HSulf-1, a known putative tumor suppressor, is a negative regulator of glycolysis. Silencing of HSulf-1 expression in OV202 cell line increased glucose uptake and lactate production by upregulating glycolytic genes such as Glut1, HKII, LDHA, as well as metabolites. Conversely, HSulf-1 overexpression in TOV21G cells resulted in the down regulation of glycolytic enzymes and reduced glycolytic phenotype, supporting the role of HSulf-1 loss in enhanced aerobic glycolysis. HSulf-1 deficiency mediated glycolytic enhancement also resulted in increased inhibitory phosphorylation of pyruvate dehydrogenase (PDH) thus blocking the entry of glucose flux into TCA cycle. Consistent with this, metabolomic and isotope tracer analysis showed reduced glucose flux into TCA cycle. Moreover, HSulf-1 loss is associated with lower oxygen consumption rate (OCR) and impaired mitochondrial function. Mechanistically, lack of HSulf-1 promotes c-Myc induction through HB EGF-mediated p-ERK activation. Pharmacological inhibition of c-Myc reduced HB-EGF induced glycolytic enzymes implicating a major role of c-Myc in loss of HSulf-1 mediated altered glycolytic pathway in OVCA. Similarly, PG545 treatment, an agent that binds to heparan binding growth factors and sequesters growth factors away from their ligand also blocked HB-EGF signaling and reduced glucose uptake in vivo in HSulf-1 deficient cells. PMID- 26378043 TI - Targeting EZH2 regulates tumor growth and apoptosis through modulating mitochondria dependent cell-death pathway in HNSCC. AB - EZH2 is a negative prognostic factor and is overexpressed or activated in most human cancers including head and neck squamous cell carcinoma (HNSCC). Analysis of The Cancer Genome Atlas (TCGA) HNSCC data indicated that EZH2 over-expression was associated with high tumor grade and conferred poor prognosis. EZH2 inhibition triggered cell apoptosis, cell cycle arrest and decreased cell growth in vitro. MICU1 (mitochondrial calcium uptake1) was shown to be down regulated when EZH2 expression was inhibited in HNSCC. When the EZH2 and MICU1 were inhibited, HNSCC cells became susceptible to cell cycle arrest and apoptosis. Mitochondrial membrane potential and cytosolic Ca2+ concentration analysis suggested that EZH2 and MICU1 were required to maintain mitochondrial membrane potential stability. A xenograft tumor model was used to confirm that EZH2 depletion inhibited HNSCC cell growth and induced tumor cell apoptosis. In summary, EZH2 is a potential anti-tumor target in HNSCC. PMID- 26378044 TI - AR-v7 protein expression is regulated by protein kinase and phosphatase. AB - Failure of androgen-targeted therapy and progression of castration-resistant prostate cancer (CRPC) are often attributed to sustained expression of the androgen receptor (AR) and its major splice variant, AR-v7. Although the new generation of anti-androgens such as enzalutamide effectively inhibits AR activity, accumulating pre-clinical and clinical evidence indicates that AR-v7 remains constitutively active in driving CRPC progression. However, molecular mechanisms which control AR-v7 protein expression remain unclear. We apply multiple prostate cancer cell models to demonstrate that enzalutamide induces differential activation of protein phosphatase-1 (PP-1) and Akt kinase depending on the gene context of cancer cells. The balance between PP-1 and Akt activation governs AR phosphorylation status and activation of the Mdm2 ubiquitin ligase. Mdm2 recognizes phosphorylated serine 213 of AR-v7, and induces AR-v7 ubiquitination and protein degradation. These findings highlight the decisive roles of PP-1 and Akt for AR-v7 protein expression and activities when AR is functionally blocked. PMID- 26378045 TI - NBAT1 suppresses breast cancer metastasis by regulating DKK1 via PRC2. AB - Long noncoding RNA NBAT1 (neuroblastoma associated transcript 1) regulates cell proliferation and invasion by interacting with PRC2 (polycomb repressive complex 2) member EZH2 (enhancer of zeste 2). Decreased expression of NBAT1 is associated with poor clinical outcome in neuroblastomas. However, the roles of NBAT1 in other cancers remain unknown. Here, we report that NBAT1 is down-regulated in various types of cancer. Particularly, reduced NBAT1 in breast cancer is associated with tumor metastasis and poor patient prognosis. In vitro, ectopic NBAT1 inhibits migration and invasion of breast cancer cells. Mechanistic study shows that NBAT1 is associated with PRC2 member EZH2 and regulates global gene expression profile. Among them, DKK1 (dickkopf WNT signaling pathway inhibitor 1) is found to be regulated by NBAT1 in a PRC2 dependent manner, and is responsible for NBAT1's effects in inhibiting migration and invasion of breast cancer cells. Taken together, our study demonstrates that long noncoding RNA NBAT1 is a potential breast cancer prognostic marker, as well as a potential therapeutic target to inhibit breast cancer metastasis. PMID- 26378046 TI - A network meta-analysis of the efficacy and side effects of UDCA-based therapies for primary sclerosing cholangitis. AB - OBJECTIVES: Therapies for treatment of patients with primary sclerosing cholangitis (PSC) include administration of ursodeoxycholic acid (UDCA) alone, or combination with metronidazole (MTZ) or mycophenolate mofetil (MMF), respectively. However, the optimum regimen still remains inconclusive. We aimed to compare interventions in terms of patient mortality or liver transplantation (MOLT), progression of liver histological stage (POLHS), serum bilirubin, alkaline phosphatase (ALP) levels and adverse events (AE). METHODS: We searched PubMed, Embase and the Cochrane Library for randomized controlled trials until 31, Jan 2015. We estimated hazard ratios (HRs), odds ratios (ORs) and mean difference (MD) between treatments on clinical outcomes. Sensitivity analyses based on the dose of UDCA, quality of trials or treatment duration were also performed. RESULTS: Ten RCTs were included. Compared with UDCA plus MTZ, UDCA (HR 0.28, 95%CI 0.01-3.41), UDCA plus MMF (HR 0.08, 95%CI 0.00-4.18), or OBS (HR 0.28, 95%CI 0.01-3.98) all provided an increased risk of MOLT. UDCA provided a significant reduction in bilirubin and ALP levels compared with OBS (MD -13.92, P < 0.001; MD -484.34, P < 0.001; respectively). With respect to POLHS, although differing not significantly, UDCA plus MTZ had a tendency to improve LHS more than UDCA (OR 1.33), UDCA plus MMF (OR 3.24) or OBS (OR 1.08). Additionally, UDCA plus MTZ (MD -544.66, P < 0.001) showed a significant reduction in ALP levels compared with OBS, but appeared to be associated with more AEs compared with UDCA (OR 5.09), UDCA plus MMF (OR 4.80) or OBS (OR 7.21). CONCLUSIONS: MTZ plus UDCA was the most effective therapy in survival rates and liver histological progression. PMID- 26378047 TI - Activation of human mast cells by retrocyclin and protegrin highlight their immunomodulatory and antimicrobial properties. AB - Preclinical evaluation of Retrocyclins (RC-100, RC-101) and Protegrin-1 (PG-1) antimicrobial peptides (AMPs) is important because of their therapeutic potential against bacterial, fungal and viral infections. Human mast cells (HMCs) play important roles in host defense and wound healing but the abilities of retrocyclins and protegrin-1 to harness these functions have not been investigated. Here, we report that chemically synthesized RC-100 and PG-1 caused calcium mobilization and degranulation in HMCs but these responses were not blocked by an inhibitor of formyl peptide receptor-like 1 (FPRL1), a known receptor for AMPs. However, RC-100 and PG-1 induced degranulation in rat basophilic leukemia (RBL-2H3) cells stably expressing Mas related G protein coupled receptor X2 (MrgX2). Chemical synthesis of these AMPs is prohibitively expensive and post-synthesis modifications (cyclization, disulfide bonds, folding) are inadequate for optimal antimicrobial activity. Indeed, we found that synthetic RC-100, which caused mast cell degranulation via MrgX2, did not display any antimicrobial activity. Green-fluorescent protein (GFP)-tagged RC-101 (analog of RC-100) and GFP-tagged PG-1 purified from transgenic plant chloroplasts killed bacteria and induced mast cell degranulation. Furthermore, GFP-PG1 bound specifically to RBL-2H3 cells expressing MrgX2. These findings suggest that retrocyclins and protegrins activate HMCs independently of FPRL1 but via MrgX2. Harnessing this novel feature of AMPs to activate mast cell's host defense/wound healing properties in addition to their antimicrobial activities expands their clinical potential. Low cost production of AMPs in plants should facilitate their advancement to the clinic overcoming major hurdles in current production systems. PMID- 26378048 TI - Involvement of p53 in insulin-like growth factor binding protein-3 regulation in the breast cancer cell response to DNA damage. AB - Chemotherapy drugs that induce apoptosis by causing DNA double-strand breaks, upregulate the tumor suppressor p53. This study investigated the regulation of the growth-regulatory protein insulin-like growth factor binding protein-3 (IGFBP 3), a p53 target, by DNA-damaging agents in breast cancer cells. IGFBP-3 was upregulated 1.4- to 13-fold in response to doxorubicin and etoposide in MCF-10A, Hs578T, MCF-7 and T47D cells, which express low to moderate basal levels of IGFBP 3. In contrast, IGFBP-3 was strongly downregulated by these agents in cells with high basal levels of IGFBP-3 (MDA-MB-231, MDA-MB-436 and MDA-MB-468). In MDA-MB 468 cells containing the R273H p53 mutation, reported to display gain-of-function properties, chemotherapy-induced suppression of IGFBP-3 was not reversed by the p53 reactivating drug, PRIMA-1, or by p53 silencing, suggesting that the decrease in IGFBP-3 following DNA damage is not a mutant p53 gain-of-function response. SiRNA-mediated downregulation of endogenous IGFBP-3 modestly attenuated doxorubicin-induced apoptosis in MDA-MB-468 and Hs578T cells. IGFBP-3 downregulation in some breast cancer cell lines in response to DNA-damaging chemotherapy may have clinical implications because suppression of IGFBP-3 may modulate the apoptotic response. These observations provide further evidence that endogenous IGFBP-3 plays a role in breast cancer cell responsiveness to DNA damaging therapy. PMID- 26378049 TI - The oncolytic peptide LTX-315 kills cancer cells through Bax/Bak-regulated mitochondrial membrane permeabilization. AB - LTX-315 has been developed as an amphipathic cationic peptide that kills cancer cells. Here, we investigated the putative involvement of mitochondria in the cytotoxic action of LTX-315. Subcellular fractionation of LTX-315-treated cells, followed by mass spectrometric quantification, revealed that the agent was enriched in mitochondria. LTX-315 caused an immediate arrest of mitochondrial respiration without any major uncoupling effect. Accordingly, LTX-315 disrupted the mitochondrial network, dissipated the mitochondrial inner transmembrane potential, and caused the release of mitochondrial intermembrane proteins into the cytosol. LTX-315 was relatively inefficient in stimulating mitophagy. Cells lacking the two pro-apoptotic multidomain proteins from the BCL-2 family, BAX and BAK, were less susceptible to LTX-315-mediated killing. Moreover, cells engineered to lose their mitochondria (by transfection with Parkin combined with treatment with a protonophore causing mitophagy) were relatively resistant against LTX-315, underscoring the importance of this organelle for LTX-315 mediated cytotoxicity. Altogether, these results support the notion that LTX-315 kills cancer cells by virtue of its capacity to permeabilize mitochondrial membranes. PMID- 26378050 TI - Pyrvinium selectively targets blast phase-chronic myeloid leukemia through inhibition of mitochondrial respiration. AB - The use of BCR-ABL1 tyrosine kinase inhibitors (TKI) has led to excellent clinical responses in patients with chronic phase chronic myeloid leukemia (CML). However these inhibitors have been less effective as single agents in the terminal blast phase (BP). We show that pyrvinium, a FDA-approved anthelminthic drug, selectively targets BP-CML CD34+ progenitor cells. Pyrvinium is effective in inducing apoptosis, inhibiting colony formation and self-renewal capacity of CD34+ cells from TKI-resistant BP-CML patients, while cord blood CD34+ are largely unaffected. The effects of pyrvinium are further enhanced upon combination with dasatinib, a second generation BCR-ABL1 TKI. In a CML xenograft model pyrvinium significantly inhibits tumor growth as a single agent, with complete inhibition in combination with dasatinib. While pyrvinium has been shown to inhibit the Wnt/beta-catenin signalling pathway via activation of casein kinase 1alpha , we find its activity in CML is not dependent on this pathway. Instead, we show that pyrvinium localizes to mitochondria and induces apoptosis by inhibiting mitochondrial respiration. Our study suggests that pyrvinium is a useful addition to the treatment armamentarium for BP-CML and that targeting mitochondrial respiration may be a potential therapeutic strategy in aggressive leukemia. PMID- 26378052 TI - An evaluation of the Essential Medicines List, Standard Treatment Guidelines and prescribing restrictions, as an integrated strategy to enhance quality, efficacy and safety of and improve access to essential medicines in Papua New Guinea. AB - The World Health Organization (WHO) has advocated the development and use of country specific Standard Treatment Guidelines (STGs) and Essential Medicines Lists (EML) as strategies to promote the rational use of medicines. When implemented effectively STGs offer many health advantages. Papua New Guinea (PNG) has official STGs and a Medical and Dental Catalogue (MDC) which serves as a national EML for use at different levels of health facilities. This study evaluated consistency between the PNG Adult STGs (2003 and 2012) and those for children (2005 and 2011) with respect to the MDCs (2002, 2012) for six chronic and/or acute diseases: asthma, arthritis, diabetes, hypertension, pneumonia and psychosis. Additionally, the potential impact of prescriber level restrictions on rational medicines use for patient's living in rural areas, where no medical officer is present, was evaluated. Almost all drugs included in the STGs for each disease state evaluated were listed in the MDCs. However, significant discrepancies occurred between the recommended treatments in the STGs with the range of related medicines listed in the MDCs. Many medicines recommended in the STGs for chronic diseases had prescriber level restrictions hindering access for most of the PNG population who live in rural and remote areas. In addition many more medicines were listed in the MDCs which are commonly used to treat arthritis, high blood pressure and psychosis than were recommended in the STGs contributing to inappropriate prescribing. We recommend the public health and rational use of medicines deficiencies associated with these findings are addressed requiring: reviewing prescriber level restrictions; updating the STGs; aligning the MDC to reflect recommendations in the STGs; establishing the process where the MDC would automatically be updated based on any changes made to the STGs; and developing STGs for higher levels of care. PMID- 26378051 TI - miRNA expression patterns in normal breast tissue and invasive breast cancers of BRCA1 and BRCA2 germ-line mutation carriers. AB - miRNA deregulation has been found to promote carcinogenesis. Little is known about miRNA deregulation in hereditary breast tumors as no miRNA expression profiling studies have been performed in normal breast tissue of BRCA1 and BRCA2 mutation carriers. miRNA profiles of 17 BRCA1- and 9 BRCA2-associated breast carcinomas were analyzed using microarrays. Normal breast tissues from BRCA1 and BRCA2 mutation carriers (both n = 5) and non-mutation carriers (n = 10) were also included. Candidate miRNAs were validated by qRT-PCR. Breast carcinomas showed extensive miRNA alteration compared to normal breast tissues in BRCA1 and BRCA2 mutation carriers. Moreover, normal breast tissue from BRCA1 mutation carriers already showed miRNA alterations compared to non-mutation carriers. Chromosomal distribution analysis showed several hotspots containing down- or up-regulated miRNAs. Pathway analysis yielded many similarities between the BRCA1 and BRCA2 axes with miRNAs involved in cell cycle regulation, proliferation and apoptosis. Lesser known pathways were also affected, including cellular movement and protein trafficking. This study provides a comprehensive insight into the potential role of miRNA deregulation in BRCA1/2-associated breast carcinogenesis. The observed extensive miRNA deregulation is likely the result of genome-wide effects of chromosomal instability caused by impaired BRCA1 or BRCA2 function. This study's results also suggest the existence of common pathways driving breast carcinogenesis in both BRCA1 and BRCA2 germ-line mutation carriers. PMID- 26378053 TI - A Case of Ectopic ACTH-Producing Pulmonary Carcinoid Arising in an Extralobar Pulmonary Sequestration. AB - Ectopic adrenocorticotrophic hormone (ACTH)-producing bronchopulmonary carcinoid arising in a bronchopulmonary sequestration is extremely rare. The case of a 67 year-old woman with a 1.7-cm nodule in the mediastinal side of the left lower lobe is presented. At 52 years of age, she was diagnosed as having ACTH-dependent Cushing's syndrome (CS). However, no ectopic source of ACTH-secretion was detected. Seven years later, she underwent a bilateral adrenalectomy because of aggravation of her health condition. This time, tumor excision was performed by thoracoscopic surgery. The tumor adhered sparsely to the mediastinal pleura and the left lower lobe and was bluntly separated from these tissues. Pathologically, the tumor was a typical carcinoid arising in an extralobar pulmonary sequestration. Immunohistochemical staining confirmed the secretion of ACTH by bronchopulmonary carcinoid tumor cells. After surgery, the serum ACTH level was almost normalized, and the dexamethasone (1 mg) suppression test showed significant suppression of ACTH. PMID- 26378054 TI - The Gross Appearance of a NUT Midline Carcinoma. AB - The NUT midline carcinoma (NMC) is a recently described and highly aggressive tumor that usually involves the head and neck and anterior mediastinum. Most patients with NMC present with metastases and are often treated with neoadjuvant chemotherapy and/or radiation therapy. As a consequence, surgical specimens are often piecemeal excisions demonstrating treatment effect. In this report, we provide what is to the best of our knowledge the first complete gross description of NMC resected in toto and without prior treatment. The patient in this case underwent a pneumonectomy for a lung mass with curative intent. On gross examination, the tumor was found to be arising from the mediastinum with a smooth border, and demonstrated only minimal invasion of the surrounding structures. However, lymphovascular invasion was present throughout and there was extensive involvement of surrounding lymph nodes. The gross appearance of the tumor in this case reaffirms that NMC is an aggressive malignancy that usually metastasizes before it invades locally. PMID- 26378055 TI - Frozen Section Interpretation of Pancreatic Margins: Subspecialized Gastrointestinal Pathologists Versus General Pathologists. AB - Intraoperative assessment of pancreatic parenchymal margin during pancreatectomies is challenging and misinterpretation by the pathologist is a cause of incorrect frozen section (FS) diagnosis. Although the current literature supports that pancreatic margin FS diagnosis and its accuracy has no impact on the patient outcome for pancreatic ductal adenocarcinoma (PDAC) patients and reexcision in an attempt to achieve a negative intraoperative pancreatic margin after positive FS is not associated with increased overall survival; still it remains a routine practice in many institutions. To this end, we sought to assess the interobserver variation and accuracy of FS diagnosis between subspecialized gastrointestinal/pancreatobiliary (GI) and general pathologists. Seventy seven consecutive pancreatic parenchymal margin FSs performed on pancreatectomies for PDAC from 2010 to 2013 were retrieved at our institution. These were retrospectively evaluated by 2 GI and 2 general pathologists independently without knowledge of the original FS diagnosis or the final diagnosis. The specificity, sensitivity, positive predictive value, negative predictive value, and accuracy of GI versus general pathologist was 97.8% versus 87.5%, 61.1% versus 66.7%, 78.6% versus 41.4%, 95% versus 95.2%, and 93.5% versus 85.1%, respectively. The interobserver agreement between GI and general pathologists was fair (kappa = .337, P < .001). The interobserver agreement between 2 GI pathologists was fair (kappa = .373, P = .0005) and between 2 general pathologists was slight (kappa = .195, P = .042). Although overall accuracy of subspecialized GI pathologists was higher than that of general pathologists, none had an accuracy of 100%. Our study reaffirms the challenging nature of these FSs. PMID- 26378056 TI - Solid Variant of Adenoid Cystic Carcinoma of the Breast: A Case Series With Proposal of a New Grading System. AB - Adenoid cystic carcinoma (ACC) of the breast is a low-grade malignancy "triple negative" breast tumor. ACC of the breast can present a great variety of morphological features having a prognostic impact. Recently, cases of ACC having solid-basaloid features (SBACC) have been described. In the present study, 6 cases of SBACC have been reported. All the cases affected female patients aged 47 to 69 years (mean = 54 years). Two patients had metastases to the axillary lymph nodes, and 2 patients experienced local recurrences. No deaths due to the tumor were observed. A review of the literature on breast SBACC showed that local recurrences and lymph node metastases are more frequent than in the ACC conventional type; nevertheless, no deaths due to the tumor are registered at the moment. On the contrary, cases of ACC with features of malignant transformation are on record. Therefore, a new grading system on breast ACC is proposed. PMID- 26378058 TI - Born from pre-eclamptic pregnancies predisposes infants to altered cortisol metabolism in the first postnatal year. AB - Pre-eclampsia leads to disturbed fetal organ development, including metabolic syndrome, attributed to altered pituitary-adrenal feedback loop. We measured cortisol metabolites in infants born from pre-eclamptic and normotensive women and hypothesised that glucocorticoid exposure would be exaggerated in the former. Twenty-four hour urine was collected from infants at months 3 and 12. Cortisol metabolites and apparent enzyme activities were analysed by gas chromatography mass spectrometry. From 3 to 12 months, excretion of THS, THF and pregnandiol had risen in both groups; THF also rose in the pre-eclamptic group. No difference was observed with respect to timing of the visit or to hypertensive status for THE or total F metabolites (P>0.05). All apparent enzymes activities, except 17alpha hydroxylase, were lower in infants at 12 compared to 3 months in the normotensive group. In the pre-eclamptic group, only 11beta-HSD activities were lower at 12 months.17alpha-hydroxylase and 11beta-HSD activities of tetrahydro metabolites were higher in the pre-eclamptic group at 3 months (P<0.05). 11beta-hydroxylase activity increased in the pre-eclamptic group at 12 months. Cortisol excretion, determined by increased 11beta-hydroxylase, compensates for high 11beta-HSD dependent cortisol degradation at 3 months and at 12 months counterbalances the reduced cortisol substrate availability in infants born from pre-eclamptic mothers. PMID- 26378059 TI - Genetic structure of the date palm (Phoenix dactylifera) in the Old World reveals a strong differentiation between eastern and western populations. AB - Since the publication of this paper, it has become apparent that an error was made in the legend to Fig. 3 and the colours referring to occidental and oriental are the wrong way round. The authors apologise for this error, and a correct version of the legend to Fig. 3 is given below. PMID- 26378057 TI - A cytoplasmic C-terminal fragment of Syndecan-1 is generated by sequential proteolysis and antagonizes Syndecan-1 dependent lung tumor cell migration. AB - Syndecan-1 is a surface expressed heparan sulphate proteoglycan, which is upregulated by several tumor types and involved in tumor cell migration and metastasis. Syndecan-1 is shed from the cell surface and the remaining transmembrane fragment undergoes intramembrane proteolysis by gamma-secretase. We here show that this generates a cytoplasmic C-terminal fragment (cCTF). In epithelial lung tumor A549 cells the endogenously produced cCTF accumulated when its proteasomal degradation was blocked with bortezomib and this accumulation was prevented by gamma-secretase inhibition. Overexpression of the cCTF suppressed migration and invasion of A549 cells. This inhibitory effect was only seen when endogenous Syndecan-1 was present, but not in Syndecan-1 deficient cells. Further, overexpression of Syndecan-1 cCTF increased the basal activation of Src kinase, focal adhesion kinase (FAK) and Rho GTPase. This was associated with increased adhesion to fibronectin and collagen G and an increased recruitment of paxillin to focal adhesions. Moreover, lung tumor formation of A549 cells in mice was reduced by overexpression of Syndecan-1 cCTF. Finally, delivery of a synthetic peptide corresponding to the Syndecan-1 cCTF suppressed A549 cell migration and increased basal phosphorylation of Src and FAK. Our data indicate that the Syndecan-1 cCTF antagonizes Syndecan-1 dependent tumor cell migration in vitro and in vivo by dysregulating proadhesive signaling pathways and suggest that the cCTF can be used as an inhibitory peptide. PMID- 26378061 TI - Assessment and management of facial nerve palsy. PMID- 26378060 TI - Restriction of dietary protein decreases mTORC1 in tumors and somatic tissues of a tumor-bearing mouse xenograft model. AB - Reduced dietary protein intake and intermittent fasting (IF) are both linked to healthy longevity in rodents, and are effective in inhibiting cancer growth. The molecular mechanisms underlying the beneficial effects of chronic protein restriction (PR) and IF are unclear, but may be mediated in part by a down regulation of the IGF/mTOR pathway. In this study we compared the effects of PR and IF on tumor growth in a xenograft mouse model of breast cancer. We also investigated the effects of PR and IF on the mechanistic Target Of Rapamycin (mTOR) pathway, inhibition of which extends lifespan in model organisms including mice. The mTOR protein kinase is found in two distinct complexes, of which mTOR complex 1 (mTORC1) is responsive to acute treatment with amino acids in cell culture and in vivo. We found that both PR and IF inhibit tumor growth and mTORC1 phosphorylation in tumor xenografts. In somatic tissues, we found that PR, but not IF, selectively inhibits the activity of the amino acid sensitive mTORC1, while the activity of the second mTOR complex, mTORC2, was relatively unaffected by PR. In contrast, IF resulted in increased S6 phosphorylation in multiple metabolic tissues. Our work represents the first finding that PR may reduce mTORC1 activity in tumors and multiple somatic tissues, and suggest that PR may represent a highly translatable option for the treatment not only of cancer, but also other age-related diseases. PMID- 26378062 TI - Multidisciplinary team meetings encourage overtreatment. PMID- 26378063 TI - Patient commentary: Consider the person alongside the pathology. PMID- 26378064 TI - Triangulating Dynamic of Clinical Laboratory Testing. PMID- 26378065 TI - Variant Profiling of Candidate Genes in Pancreatic Ductal Adenocarcinoma. AB - BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis. Variant profiling is crucial for developing personalized treatment and elucidating the etiology of this disease. METHODS: Patients with PDAC undergoing surgery from 2007 to 2012 (n = 73) were followed from diagnosis until death or the end of the study. We applied an anchored multiplex PCR (AMP)-based next-generation sequencing (NGS) method to a panel of 65 selected genes and assessed analytical performance by sequencing a quantitative multiplex DNA reference standard. In clinical PDAC samples, detection of low-level KRAS (Kirsten rat sarcoma viral oncogene homolog) mutations was validated by allele-specific PCR and digital PCR. We compared overall survival of patients according to KRAS mutation status by log rank test and applied logistic regression to evaluate the association between smoking and tumor variant types. RESULTS: The AMP-based NGS method could detect variants with allele frequencies as low as 1% given sufficient sequencing depth (>1500*). Low-frequency KRAS G12 mutations (allele frequency 1%-5%) were all confirmed by allele-specific PCR and digital PCR. The most prevalent genetic alterations were in KRAS (78% of patients), TP53 (tumor protein p53) (25%), and SMAD4 (SMAD family member 4) (8%). Overall survival in T3-stage PDAC patients differed among KRAS mutation subtypes (P = 0.019). Transversion variants were more common in ever-smokers than in never-smokers (odds ratio 5.7; 95% CI 1.2 27.8). CONCLUSIONS: The AMP-based NGS method is applicable for profiling tumor variants. Using this approach, we demonstrated that in PDAC patients, KRAS mutant subtype G12V is associated with poorer survival, and that transversion variants are more common among smokers. PMID- 26378066 TI - Does Resuscitation Training Reduce Neonatal Deaths in Low-Resource Communities? A Systematic Review of the Literature. AB - Every year, nearly 1 million babies succumb to birth asphyxia (BA) within the Asia-Pacific region. The present study sought to determine whether educational interventions containing some element of resuscitation training would decrease the relative risk (RR) of neonatal mortality attributable to BA in low-resource communities. We systematically reviewed 3 electronic databases and identified 14 relevant reports. For community deliveries, providing traditional birth attendants (TBAs) with neonatal resuscitation training modestly reduced the RR in 3 of 4 studies. For institutional deliveries, training a range of clinical staff clearly reduced the RR within 2 of 8 studies. When resuscitation-specific training was directed to community and institutional health care workers, a slight benefit was observed in 1 of 2 studies. Specific training in neonatal resuscitation appears most effective when provided to TBAs (specifically, those presented with ongoing opportunities to review and update their skills), but this particular intervention alone may not appreciably reduce mortality. PMID- 26378067 TI - Efficacy of early intravenous bolus oxycodone or fentanyl in emergence from general anaesthesia and postoperative analgesia following laparoscopic cholecystectomy: A randomized trial. AB - OBJECTIVES: To compare prospectively the efficacy of early intravenous bolus of oxycodone or fentanyl in providing analgesia at emergence from general anaesthesia following laparoscopic cholecystectomy. METHODS: Patients were randomly assigned to receive either 0.08 mg/kg oxycodone (Group O) or 1 ug/kg fentanyl (Group F), 20 min before the end of surgery. Postoperative pain was evaluated using a visual analogue scale (VAS). The time to first postoperative analgesic dose, requirement for analgesia and side-effects were assessed in the postanaesthesia care unit (PACU). RESULTS: The VAS scores at 0 min and 30 min and requirement for analgesia were significantly lower in Group O (n = 28) than in Group F (n = 26). The time to first analgesia dose was significantly longer in Group O than Group F. There were no significant between-group differences in the incidence of side-effects. CONCLUSIONS: Oxycodone relieves immediate postoperative pain significantly better than fentanyl, and is not associated with an increase in side-effects in patients undergoing laparoscopic cholecystectomy. PMID- 26378068 TI - Analysis of corneal topography in patients with pure microphthalmia in Eastern China. AB - OBJECTIVES: To determine the typical corneal changes in pure microphthalmia using a corneal topography system and identify characteristics that may assist in early diagnosis. METHODS: Patients with pure microphthalmia and healthy control subjects underwent corneal topography analysis (Orbscan IIZ(r) Corneal Topography System; Bausch and Lomb, Bridgewater, NJ, USA) to determine degree of corneal astigmatism (mean A), simulation of corneal astigmatism (sim A), mean keratometry (mean K), simulated keratometry (sim K), irregularities in the 3 - and 5-mm zone, and mean thickness of nine distinct corneal regions. RESULTS: Patients with pure microphthalmia (n = 12) had significantly higher mean K, sim K, mean A, sim A, 3.0 mm irregularity and 5.0 mm irregularity, and exhibited significantly more false keratoconus than controls (n = 12). There was a significant between-group difference in the morphology of the anterior corneal surface and the central curvature of the cornea. CONCLUSIONS: Changes in corneal morphology observed in this study could be useful in borderline situations to confirm the diagnosis of pure microphthalmia. PMID- 26378069 TI - An uncomfortable hip exacerbated by exercise. PMID- 26378070 TI - Addressing vaccine hesitancy and refusal in Canada. PMID- 26378071 TI - Anatomic variations of internal jugular vein, inferior petrosal sinus and its confluence pattern: Implications in inferior petrosal sinus catheterization. AB - OBJECTIVE: The purpose of this study is to describe anatomic variations of the internal jugular vein (IJV), inferior petrosal sinus (IPS) and their confluence pattern and implications in IPS catheterization. The anatomic route of IPS after going out of the cranium and its confluence patterns with IJV and will supply knowledge about typing of IPS-IJV junction. METHOD: A review of the literature was performed. RESULTS: There might be different routes for entering the intracranial segment of the IPS and multislice spiral computed tomography (MSCT) is effective in identifying the confluences of the IPS with the IJV and their courses. It is important to find the confluence of IPS with IJV for diagnosis and treatment of intracranial lesions via venous route. Meanwhile, IPS diameter at the confluence can significantly affect success of catheterization. CONCLUSION: The classification and the theory of the development of the caudal end of the IPS may be useful in establishing treatment strategies that involve endovascular manipulation via the IPS. PMID- 26378072 TI - Signal Strength and Metabolic Requirements Control Cytokine-Induced Th17 Differentiation of Uncommitted Human T Cells. AB - IL-17 production defines Th17 cells, which orchestrate immune responses and autoimmune diseases. Human Th17 cells can be efficiently generated with appropriate cytokines from precommitted precursors, but the requirements of uncommitted T cells are still ill defined. In standard human Th17 cultures, IL-17 production was restricted to CCR6(+)CD45RA(+) T cells, which expressed CD95 and produced IL-17 ex vivo, identifying them as Th17 memory stem cells. Uncommitted naive CD4(+) T cells upregulated CCR6, RORC2, and IL-23R expression with Th17 promoting cytokines but in addition required sustained TCR stimulation, late mammalian target of rapamycin (mTOR) activity, and HIF-1alpha to produce IL-17. However, in standard high-density cultures, nutrients like glucose and amino acids became progressively limiting, and mTOR activity was consequently not sustained, despite ongoing TCR stimulation and T cell proliferation. Sustained, nutrient-dependent mTOR activity also induced spontaneous IL-22 and IFN-gamma production, but these cytokines had also unique metabolic requirements. Thus, glucose promoted IL-12-independent Th1 differentiation, whereas aromatic amino acid-derived AHR ligands were selectively required for IL-22 production. The identification of Th17 memory stem cells and the stimulation requirements for induced human Th17/22 differentiation have important implications for T cell biology and for therapies targeting the mTOR pathway. PMID- 26378074 TI - Importance of Endosomal Cathelicidin Degradation To Enhance DNA-Induced Chicken Macrophage Activation. AB - Cathelicidins are essential in the protection against invading pathogens through both their direct antimicrobial activity and their immunomodulatory functions. Although cathelicidins are known to modulate activation by several TLR ligands, little is known about their influence on DNA-induced macrophage activation. In this study, we explored the effects of cathelicidins on DNA-induced activation of chicken macrophages and elucidated the intracellular processes underlying these effects. Our results show that chicken cathelicidin (CATH)-2 strongly enhances DNA-induced activation of both chicken and mammalian macrophages because of enhanced endocytosis of DNA-CATH-2 complexes. After endocytosis, DNA is liberated from the complex because of proteolytic breakdown of CATH-2, after which TLR21 is activated. This leads to increased cytokine expression and NO production. Through the interaction with DNA, CATH-2 can play an important role in modulating the immune response at sites of infection. These observations underline the importance of cathelicidins in sensing bacterial products and regulating immune responses. PMID- 26378073 TI - A Stromal Cell Niche for Human and Mouse Type 3 Innate Lymphoid Cells. AB - Adaptive immunity critically depends on the functional compartmentalization of secondary lymphoid organs. Mesenchymal stromal cells create and maintain specialized niches that support survival, activation, and expansion of T and B cells, and integrated analysis of lymphocytes and their niche has been instrumental in understanding adaptive immunity. Lymphoid organs are also home to type 3 innate lymphoid cells (ILC3), innate effector cells essential for barrier immunity. However, a specialized stromal niche for ILC3 has not been identified. A novel lineage-tracing approach now identifies a subset of murine fetal lymphoid tissue organizer cells that gives rise exclusively to adult marginal reticular cells. Moreover, both cell types are conserved from mice to humans and colocalize with ILC3 in secondary lymphoid tissues throughout life. In sum, we provide evidence that fetal stromal organizers give rise to adult marginal reticular cells and form a dedicated stromal niche for innate ILC3 in adaptive lymphoid organs. PMID- 26378075 TI - Adaptive Immunity to Leukemia Is Inhibited by Cross-Reactive Induced Regulatory T Cells. AB - BCR-ABL(+) acute lymphoblastic leukemia patients have transient responses to current therapies. However, the fusion of BCR to ABL generates a potential leukemia-specific Ag that could be a target for immunotherapy. We demonstrate that the immune system can limit BCR-ABL(+) leukemia progression although ultimately this immune response fails. To address how BCR-ABL(+) leukemia escapes immune surveillance, we developed a peptide: MHC class II tetramer that labels endogenous BCR-ABL-specific CD4(+) T cells. Naive mice harbored a small population of BCR-ABL-specific T cells that proliferated modestly upon immunization. The small number of naive BCR-ABL-specific T cells was due to negative selection in the thymus, which depleted BCR-ABL-specific T cells. Consistent with this observation, we saw that BCR-ABL-specific T cells were cross reactive with an endogenous peptide derived from ABL. Despite this cross reactivity, the remaining population of BCR-ABL reactive T cells proliferated upon immunization with the BCR-ABL fusion peptide and adjuvant. In response to BCR-ABL(+) leukemia, BCR-ABL-specific T cells proliferated and converted into regulatory T (Treg) cells, a process that was dependent on cross-reactivity with self-antigen, TGF-beta1, and MHC class II Ag presentation by leukemic cells. Treg cells were critical for leukemia progression in C57BL/6 mice, as transient Treg cell ablation led to extended survival of leukemic mice. Thus, BCR-ABL(+) leukemia actively suppresses antileukemia immune responses by converting cross reactive leukemia-specific T cells into Treg cells. PMID- 26378076 TI - B7-H1 Selectively Controls TH17 Differentiation and Central Nervous System Autoimmunity via a Novel Non-PD-1-Mediated Pathway. AB - It is currently acknowledged that TH17 cells are critically involved in the pathogenesis of autoimmune diseases such as multiple sclerosis (MS). In this article, we demonstrate that signals delivered by the coinhibitory molecule B7 homologue 1 (B7-H1) via a B7-homologue 1 mouse-IgG2aFc (B7-H1-Ig) fusion protein nearly abolish TH17, but not TH1 and TH2, differentiation via direct interaction with the T cell. These effects were equally pronounced in the absence of programmed death-1 or B7.1 and B7.2 on the T cell side, thus providing clear evidence that B7-H1 modulates T cell differentiation via a novel receptor. Mechanistically, B7-H1 interfered with early TCR-mediated signaling and cytokine mediated induction of the TH17-determining transcription factors retinoic acid related orphan receptor gamma t and IFN regulator factor-4 in a programmed death 1 and B7-independent fashion. In an animal model of MS, active myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis, B7-H1-Ig exhibited a significant and long-lasting effect on disease severity upon administration during the first 5 d of the priming phase, which was accompanied by reduced TH17 responses in the periphery and within the CNS. Importantly, B7-H1 Ig was even capable of interfering with T cell encephalitogenicity when interaction with the T cells occurred after priming using an adoptive transfer experimental autoimmune encephalomyelitis model. In line with this, both naive human CD4(+) T cells and differentiated TH17 effector cells from MS patients were highly sensitive toward B7-H1-Ig-mediated TH17 suppression. Together, we propose the existence of a novel B7-H1-mediated immune-regulatory pathway in T cells, which selectively limits murine and human TH17 cell responses and might be therapeutically exploited to control TH17-mediated autoimmunity. PMID- 26378077 TI - Deleted in Breast Cancer 1 Suppresses B Cell Activation through RelB and Is Regulated by IKKalpha Phosphorylation. AB - Alternative NF-kappaB signaling is crucial for B cell activation and Ig production, and it is mainly regulated by the inhibitor of kappa B kinase (IKK) regulatory complex. Dysregulation of alternative NF-kappaB signaling in B cells could therefore lead to hyperactive B cells and Ig overproduction. In our previous, study we found that deleted in breast cancer 1 (DBC1) is a suppressor of the alternative NF-kappaB pathway to attenuate B cell activation. In this study, we report that loss of DBC1 results in spontaneous overproduction of Ig in mice after 10 mo of age. Using a double mutant genetic model, we confirm that DBC1 suppresses B cell activation through RelB inhibition. At the molecular level, we show that DBC1 interacts with alternative NF-kappaB members RelB and p52 through its leucine zipper domain. In addition, phosphorylation of DBC1 at its C terminus by IKKalpha facilitates its interaction with RelB and IKKalpha, indicating that DBC1-mediated suppression of alternative NF-kappaB is regulated by IKKalpha. Our results define the molecular mechanism of DBC1 inhibition of alternative NF-kappaB activation in suppressing B cell activation. PMID- 26378078 TI - A Tumor Mitochondria Vaccine Protects against Experimental Renal Cell Carcinoma. AB - Mitochondria provide energy for cells via oxidative phosphorylation. Reactive oxygen species, a byproduct of this mitochondrial respiration, can damage mitochondrial DNA (mtDNA), and somatic mtDNA mutations have been found in all colorectal, ovarian, breast, urinary bladder, kidney, lung, and pancreatic tumors studied. The resulting altered mitochondrial proteins or tumor-associated mitochondrial Ags (TAMAs) are potentially immunogenic, suggesting that they may be targetable Ags for cancer immunotherapy. In this article, we show that the RENCA tumor cell line harbors TAMAs that can drive an antitumor immune response. We generated a cellular tumor vaccine by pulsing dendritic cells with enriched mitochondrial proteins from RENCA cells. Our dendritic cell-based RENCA mitochondrial lysate vaccine elicited a cytotoxic T cell response in vivo and conferred durable protection against challenge with RENCA cells when used in a prophylactic or therapeutic setting. By sequencing mtDNA from RENCA cells, we identified two mutated molecules: COX1 and ND5. Peptide vaccines generated from mitochondrial-encoded COX1 but not from ND5 had therapeutic properties similar to RENCA mitochondrial protein preparation. Thus, TAMAs can elicit effective antitumor immune responses, potentially providing a new immunotherapeutic strategy to treat cancer. PMID- 26378081 TI - Vertigo/dizziness in pediatric emergency department: Five years' experience. AB - BACKGROUND: Vertigo/Dizziness in childhood is not a rare cause of visits to the emergency department (ED). We analyzed a selected group with vertigo/dizziness to identify signs and symptoms that may help to guide the diagnostic approach and management. METHODS: A total of 616 children admitted for vertigo to the ED over a five-year period were retrospectively reviewed. Their medical history, clinical characteristics, laboratory and neuroimaging tests, final diagnoses and management were analyzed. RESULTS: Migraine and syncope were the most frequent causes. Two patients were affected by life-threatening cardiac syncope, while structural life-threatening central nervous system diseases were found in 15 patients, none of whom presented with vertigo as an isolated clinical finding. CONCLUSIONS: Most cases of vertigo/dizziness in childhood that consist mainly of migraine and syncope are of benign origin. The prompt identification of neurological or cardiological signs or symptoms associated with vertigo in children is mandatory to rule out life-threatening conditions. PMID- 26378082 TI - Interictal photosensitivity associates with altered brain structure in patients with episodic migraine. AB - BACKGROUND: Migraine attacks manifest with hypersensitivities to light, sound, touch and odor. Some people with migraine have photosensitivity between migraine attacks, suggesting persistent alterations in the integrity of brain regions that process light. Although functional neuroimaging studies have shown visual stimulus induced "hyperactivation" of visual cortex regions in migraineurs between attacks, whether photosensitivity is associated with alterations in brain structure is unknown. METHODS: Levels of photosensitivity were evaluated using the Photosensitivity Assessment Questionnaire in 48 interictal migraineurs and 48 healthy controls. Vertex-by-vertex measurements of cortical thickness were assessed in 28 people with episodic migraine who had interictal photosensitivity (mean age = 35.0 years, SD = 12.1) and 20 episodic migraine patients without symptoms of interictal photosensitivity (mean age = 36.0 years, SD = 11.4) using a general linear model design. RESULTS: Migraineurs have greater levels of interictal photosensitivity relative to healthy controls. Relative to migraineurs without interictal photosensitivity, migraineurs with interictal photosensitivity have thicker cortex in several brain areas including the right lingual, isthmus cingulate and pericalcarine regions, and the left precentral, postcentral and supramarginal regions. CONCLUSION: Episodic migraineurs with interictal photosensitivity have greater cortical thickness in the right parietal-occipital and left fronto-parietal regions, suggesting that persistent light sensitivity is associated with underlying structural alterations. PMID- 26378079 TI - Histone Deacetylases in Bone Development and Skeletal Disorders. AB - Histone deacetylases (Hdacs) are conserved enzymes that remove acetyl groups from lysine side chains in histones and other proteins. Eleven of the 18 Hdacs encoded by the human and mouse genomes depend on Zn(2+) for enzymatic activity, while the other 7, the sirtuins (Sirts), require NAD2(+). Collectively, Hdacs and Sirts regulate numerous cellular and mitochondrial processes including gene transcription, DNA repair, protein stability, cytoskeletal dynamics, and signaling pathways to affect both development and aging. Of clinical relevance, Hdacs inhibitors are United States Food and Drug Administration-approved cancer therapeutics and are candidate therapies for other common diseases including arthritis, diabetes, epilepsy, heart disease, HIV infection, neurodegeneration, and numerous aging-related disorders. Hdacs and Sirts influence skeletal development, maintenance of mineral density and bone strength by affecting intramembranous and endochondral ossification, as well as bone resorption. With few exceptions, inhibition of Hdac or Sirt activity though either loss-of function mutations or prolonged chemical inhibition has negative and/or toxic effects on skeletal development and bone mineral density. Specifically, Hdac/Sirt suppression causes abnormalities in physiological development such as craniofacial dimorphisms, short stature, and bone fragility that are associated with several human syndromes or diseases. In contrast, activation of Sirts may protect the skeleton from aging and immobilization-related bone loss. This knowledge may prolong healthspan and prevent adverse events caused by epigenetic therapies that are entering the clinical realm at an unprecedented rate. In this review, we summarize the general properties of Hdacs/Sirts and the research that has revealed their essential functions in bone forming cells (e.g., osteoblasts and chondrocytes) and bone resorbing osteoclasts. Finally, we offer predictions on future research in this area and the utility of this knowledge for orthopedic applications and bone tissue engineering. PMID- 26378084 TI - Dentoskeletal effects during Herbst-Multibracket appliance treatment: a comparison of lingual and labial approaches. AB - OBJECTIVES: To analyse and compare the effects during Herbst treatment (Tx) when combined with lingual (completely customized) or labial (straight-wire) multibracket appliances (MBA). SUBJECTS AND METHODS: 18 Class II division 1 patients (Overjet >= 5mm, Class II molar relationship >= 0.5 cusp width bilaterally or 1 cusp width unilaterally, median age 16.0 years) treated with lingual (completely customized) MBA in combination with a Herbst appliance were matched (sagittal molar relationship and skeletal maturity) to 18 Class II division 1 Herbst patients treated with labial (straight-wire) MBA. Lateral cephalograms from before, during and after all active Tx were analysed using the SO-analysis and standard cephalometric variables. RESULTS: During the Herbst phase (LINGUAL: mean = 13.9 months, LABIAL: mean = 8.5 months) smaller average Overjet and molar relationship changes were seen in the LINGUAL (5.3mm/4.4mm) than in the LABIAL (8.0mm/5.9mm) group. This was due to the fact that the LABIAL patients were treated to overcorrected sagittal relationships. During the total Tx period (Herbst + MBA; LINGUAL: mean = 3.1 years, LABIAL: mean = 1.9 years) the average amounts of Overjet and molar relationship changes were similar in both groups (LINGUAL: 4.0mm/3.3mm, LABIAL: 5.1mm/3.7mm). Overjet correction was achieved by 45% (LINGUAL) and 37% (LABIAL) skeletal changes; the respective amounts for molar relationship correction were 55% (LINGUAL) and 51% (LABIAL). CONCLUSION: For most variables, similar effects occurred during Herbst Tx whether combined with lingual (completely customized) or labial (straight-wire) MBA. PMID- 26378083 TI - Evaluation of skeletal maturity using maxillary canine, mandibular second and third molar calcification stages. AB - OBJECTIVE: The objective of this study was to evaluate whether the calcification stages of maxillary canine, mandibular second molar, and mandibular third molar can be used for assessment of growth phase. MATERIALS AND METHODS: The study group consisted of 274 subjects. Pre-treatment digital panoramic and lateral cephalometric radiographs of the patients were analysed. The patients' age was ranging from 7 to 19 years. Right maxillary canine, mandibular second molar and third molar were used as a sample. The teeth mineralization was assessed using modification of Gleiser and Hunt method. The skeletal maturation was assessed by the cervical vertebrae maturation (CVM) method. RESULTS: A significant association was found between CVM stage 2 and maxillary canine (UC) stage 4, mandibular second molar (LM2) stage 4, and mandibular third molar (LM3) stage 1. CVM stage 3 corresponded with UC stage 5, LM2 stage 5, LM3 stage 2. CVM stage 4 matched with UC stage 5, LM2 stage 6 and LM3 stage 3. The highest correlations between CVM and calcification stages were in the group of the maxillary canine (r = 0.812, P < 0.01) and mandibular second molar (r = 0.824, P < 0.01). LIMITATIONS: Limitation of our study was that the study sample was not very big and the distribution value in the groups was very high, so it was impossible to check more statistical parameters. CONCLUSIONS: The calcification stages of UC, LM2, and LM3 as indicators of skeletal maturity could be clinically used with caution, until this method is verified with a larger sample group. PMID- 26378085 TI - Accuracy of a three-dimensional dentition model digitized from an interocclusal record using a non-contact surface scanner. AB - OBJECTIVES: For orthodontic treatment, it is important to assess the dental morphology, as well as the position and inclination of teeth. The aim of this article was to develop an efficient and accurate method for the three-dimensional (3D) imaging of the maxillary and mandibular dental morphology by measuring interocclusal records using an optical scanner. MATERIALS AND METHODS: The occlusal and incisal morphology of participants was registered in the intercuspal position using a hydrophilic vinyl polysiloxane and digitized into 3D models using an optical scanner. Impressions were made of the maxilla and mandible in alginate materials in order to fabricate plaster models and created into 3D models using the optical scanner based on the principal triangulation method. The occlusal and incisal areas of the interocclusal records were retained. The buccal and lingual areas were added to these regions entirely by the 3D model of the plaster model. The accuracy of this method was evaluated for each tooth, with the dental cast 3D models used as controls. RESULTS: The 3D model created from the interocclusal record and the plaster model of the dental morphology was analysed in 3D software. The difference between the controls and the 3D models digitized from the interocclusal records was 0.068+/-0.048mm, demonstrating the accuracy of this method. LIMITATIONS: The presence of severe crowding may compromise the ability to separate each tooth and digitize the dental morphology. CONCLUSIONS: The digitization method in this study provides sufficient accuracy to visualize the dental morphology, as well as the position and inclination of these teeth. PMID- 26378086 TI - Letters to the Editor. PMID- 26378087 TI - Treating elevated LDL cholesterol in patients with low short-term risk: Decision making at the limits of EBM. PMID- 26378088 TI - Efficacy of Warm Needle Moxibustion on Lumbar Disc Herniation: A Meta-Analysis. AB - BACKGROUND: Clinical studies on the efficacy of warm needle moxibustion to treat lumbar disc herniation are increasing, while studies on the assessment of its efficacy are still lacking. OBJECTIVE: To assess the clinical effect of warm needle moxibustion on lumbar disc herniation. METHODS: We searched relevant trials that compared warm needle moxibustion with other methods for lumbar disc herniation from 9 databases. RESULTS: Warm needle moxibustion showed statistical significance efficiency rate compared with acupuncture and manipulation but had a similar rate with nonsteroidal anti-inflammatory drugs (NSAIDs). It showed a statistically significanty excellent rate when compared with acupuncture and manipulation but had a similar rate with NSAIDs. Regarding Japanese Orthopedic Association scores, it showed statistical significance with acupuncture and manipulation, but the rate was similar with Chinese medicine and NSAIDs. Regarding visual analog scale score, it demonstrated statistical significance when compared with acupuncture, manipulation, and NSAIDs but had a similar rate with Chinese medicine. CONCLUSION: Warm needle moxibustion is superior to acupuncture and manipulation in terms of efficiency rate, excellent rate, and controlling of pain for lumbar disc herniation, but it is similar when compared with NSAIDs and Chinese medicine. PMID- 26378089 TI - Adding the implantable cardioverter-defibrillator to cardiac resynchronization therapy is associated with improved long-term survival in ischaemic, but not in non-ischaemic cardiomyopathy. AB - AIMS: Cardiac resynchronization therapy (CRT) improves symptoms, left ventricular function, and survival in patients with heart failure (HF) and wide QRS. The benefit of adding implantable cardioverter-defibrillator (ICD) backup is debated. We analysed the long-term outcome of patients with HF due to ischaemic cardiomyopathy (ICM) or non-ischaemic cardiomyopathy (NICM) treated with a CRT device with or without defibrillator backup. METHODS AND RESULTS: In this observational study, consecutive patients with an ejection fraction <=35% and QRS width >=120 ms receiving a CRT device at Aarhus University Hospital, Denmark from 2000 to 2010 were included. Baseline characteristics were retrieved from patient files and survival data were obtained from the Danish Civil Registration System. The primary outcome was all-cause mortality. The effect of ICD backup was estimated using Cox proportional hazards model, and the multivariate analyses were adjusted for a priori selected variables. We included 917 HF patients, 427 with NICM, and 490 with ICM. Median follow-up was 4.0 years. Adjusted hazard ratio (aHR) for all-cause mortality was 0.76 [95% confidence interval (95% CI), 0.60-0.97; P = 0.03] in all patients; 0.96 (95% CI, 0.60-1.51; P = 0.85) in patients with NICM, and 0.74 (95% CI, 0.56-0.97; P = 0.03) in patients with ICM. In patients with NICM, ICD backup seemed to be associated with improved survival among non-responders to CRT (P = 0.08), but not among responders (P = 0.61). CONCLUSION: Adding an ICD backup is associated with better survival in CRT recipients. This effect was evident among patients with ICM, but not in patients with NICM. PMID- 26378091 TI - Procalcitonin as a Serum Biomarker for Differentiation of Bacterial Meningitis From Viral Meningitis in Children: Evidence From a Meta-Analysis. AB - Several studies have explored the use of serum procalcitonin (PCT) in differentiating between bacterial and viral etiologies in children with suspected meningitis. We pooled these studies into a meta-analysis to determine the PCT diagnostic accuracy. All major databases were searched through March 2015. No date or language restrictions were applied. Eight studies (n = 616 pediatric patients) were included. Serum PCT assay was found to be very accurate for differentiating the etiology of pediatric meningitis with pooled sensitivity and specificity of 0.96 (95% CI = 0.92-0.98) and 0.89 (95% CI = 0.86-0.92), respectively. The pooled positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio (DOR), and area under the curve (AUC) for PCT were 7.5 (95% CI = 5.6-10.1), 0.08(95% CI = 0.04-0.14), 142.3 (95% CI = 59.5-340.4), and 0.97 (SE = 0.01), respectively. In 6 studies, PCT was found to be superior than CRP, whose DOR was only 16.7 (95%CI = 8.8-31.7). Our meta-analysis demonstrates that serum PCT assay is a highly accurate and powerful test for rapidly differentiating between bacterial and viral meningitis in children. PMID- 26378090 TI - Long-term outcomes and prognostic factors in 78 Japanese patients with advanced pancreatic neuroendocrine neoplasms: a single-center retrospective study. AB - OBJECTIVE: Despite an increase in the number of Japanese patients with pancreatic neuroendocrine neoplasms, long-term outcomes and prognostic factors, especially for those with advanced disease, remain unclear. METHODS: We retrospectively reviewed the medical records of 78 patients with unresectable pancreatic neuroendocrine neoplasms treated at our hospital from January 1987 to March 2015. Survival analyses were performed using Kaplan-Meier methods. Prognostic significance of several clinicopathological factors were analyzed by univariate and multivariate analyses using a Cox regression model. RESULTS: Median overall survivals of pancreatic neuroendocrine tumor (n = 64) and pancreatic neuroendocrine carcinoma (n = 14) were 83.7 and 9.1 months, respectively (hazard ratio: 0.02, 95% confidence interval: 0.01-0.08, P < 0.001). Although no significant differences were observed using a Ki-67 cut-off value of 2% (hazard ratio: 0.46, 95% confidence interval: 0.16-1.13, P = 0.0989), a Ki-67 cut-off of 10% was a significant predictor in patients with pancreatic neuroendocrine tumor (hazard ratio: 9.95, 95% confidence interval, 3.01-32.97, P < 0.001). Treatment after the advent of targeted therapy (hazard ratio: 0.07, 95% confidence interval: 0.03-0.19, P < 0.001) and the presence of bone metastases (hazard ratio: 4.38, 95% confidence interval: 1.42-11.29, P = 0.013) were significant prognostic factors in patients with pancreatic neuroendocrine tumor evaluated by univariate analysis. Multivariate analysis also revealed that a Ki-67 index >=10% (hazard ratio: 38.8, 95% confidence interval: 8.42-226.62, P < 0.001), approval of targeted therapy (hazard ratio: 0.02, 95% confidence interval: 0.00-0.11, P < 0.001) and bone metastases (hazard ratio: 5.56, 95% confidence interval: 1.10 24.00, P = 0.039) were independent prognostic factors. CONCLUSIONS: We elucidated the long-term outcomes and prognostic factors in Japanese patients with advanced pancreatic neuroendocrine neoplasms. PMID- 26378092 TI - An Adolescent Male With a Rash. PMID- 26378093 TI - Gender Differences in Recovery From Sports-Related Concussion in Adolescents. PMID- 26378094 TI - Modification of platelet proteins by malondialdehyde: prevention by dicarbonyl scavengers. AB - The thromboxane synthase converts prostaglandin H(2) to thromboxane A(2) and malondialdehyde (MDA) in approximately equimolar amounts. A reactive dicarbonyl, MDA forms covalent adducts of amino groups, including the epsilon-amine of lysine, but the importance of this reaction in platelets was unknown. Utilizing a novel LC/MS/MS method for analysis of one of the MDA adducts, the dilysyl-MDA cross-link, we demonstrated that dilysyl-MDA cross-links in human platelets are formed following platelet activation via the cyclooxygenase (COX)-1/thromboxane synthase pathway. Salicylamine and analogs of salicylamine were shown to react with MDA preferentially, thereby preventing formation of lysine adducts. Dilysyl MDA cross-links were measured in two diseases known to be associated with increased platelet activation. Levels of platelet dilysyl-MDA cross-links were increased by 2-fold in metabolic syndrome relative to healthy subjects, and by 1.9-fold in sickle cell disease (SCD). In patients with SCD, the reduction of platelet dilysyl-MDA cross-links following administration of nonsteroidal anti inflammatory drug provided evidence that MDA modifications of platelet proteins in this disease are derived from the COX pathway. In summary, MDA adducts of platelet proteins that cross-link lysines are formed on platelet activation and are increased in diseases associated with platelet activation. These protein modifications can be prevented by salicylamine-related scavengers. PMID- 26378095 TI - Reduction in PCSK9 levels induced by anacetrapib: an off-target effect? PMID- 26378096 TI - Recruiting and retaining young adults in a weight gain prevention trial: Lessons learned from the CHOICES study. AB - BACKGROUND/AIMS: Young adults are at risk of weight gain, but little is known about designing effective weight control trials for young adults or how to recruit and retain participants in these programs. The Choosing Healthy Options in College Environments and Settings (CHOICES) study evaluated the effectiveness of a weight gain prevention intervention for 2-year college students. We describe the methods used to recruit and retain the colleges and their students, describe the sample and discuss recommendations for future studies. METHODS: Students were recruited into a 24-month trial of a weight control intervention with assessment periods at baseline, 4-, 12- and 24-month follow-up. RESULTS: We successfully recruited 441 students through partnerships with three 2-year colleges through a variety of campus-based methods. Ultimately, 83.4% of the randomized cohort participated in the 24-month assessment period. Those retained more often were White (p = 0.03) compared to those who dropped out or were lost to follow-up; no other socio-demographic factor (e.g. gender, ethnicity and education), body mass index, body fat, waist circumference or weight status was observed to differ between randomly assigned groups. CONCLUSION: Two-year colleges and their students are interested in participating in weight-related trials and partnering with universities for research. Researchers must work closely with administrators to identify benefits to their institutions and to resolve student-level barriers to recruitment and retention. Our experiences from the Choosing Healthy Options in College Environments and Settings study should be useful in identifying effective recruitment and retention methods for weight gain prevention trials among young adults. PMID- 26378097 TI - Deltamethrin Binding to Triatoma infestans (Hemiptera: Reduviidae) Lipoproteins. Analysis by Solvent Bar Microextraction Coupled to Gas Chromatography. AB - The binding of deltamethrin (DLM) to the hemipteran Triatoma infestans (Klug) hemolymph lipoproteins was evaluated in vitro. After DLM incubation with the insect hemolymph, lipoproteins were fractioned by ultracentrifugation. DLM binding was analyzed by a microextractive technique-solvent bar microextraction-a solventless methodology to extract DLM from each lipoprotein fraction. This is a novel use of the technique applied to extract an insecticide from an insect fluid. Capillary gas chromatography with microelectron capture detection was used to detect DLM bound by the T. infestans hemolymph lipoproteins and to identify the preferred DLM carrier. We show that Lp and VHDLp I lipoproteins are mainly responsible for DLM transport in T. infestans, both in DLM-resistant and DLM susceptible bugs. Our results also indicate that DLM amounts transported are not related to DLM susceptibility. PMID- 26378099 TI - Aspen Tension Wood Fibers Contain beta-(1---> 4)-Galactans and Acidic Arabinogalactans Retained by Cellulose Microfibrils in Gelatinous Walls. AB - Contractile cell walls are found in various plant organs and tissues such as tendrils, contractile roots, and tension wood. The tension-generating mechanism is not known but is thought to involve special cell wall architecture. We previously postulated that tension could result from the entrapment of certain matrix polymers within cellulose microfibrils. As reported here, this hypothesis was corroborated by sequential extraction and analysis of cell wall polymers that are retained by cellulose microfibrils in tension wood and normal wood of hybrid aspen (Populus tremula * Populus tremuloides). beta-(1->4)-Galactan and type II arabinogalactan were the main large matrix polymers retained by cellulose microfibrils that were specifically found in tension wood. Xyloglucan was detected mostly in oligomeric form in the alkali-labile fraction and was enriched in tension wood. beta-(1->4)-Galactan and rhamnogalacturonan I backbone epitopes were localized in the gelatinous cell wall layer. Type II arabinogalactans retained by cellulose microfibrils had a higher content of (methyl)glucuronic acid and galactose in tension wood than in normal wood. Thus, beta-(1->4) galactan and a specialized form of type II arabinogalactan are trapped by cellulose microfibrils specifically in tension wood and, thus, are the main candidate polymers for the generation of tensional stresses by the entrapment mechanism. We also found high beta-galactosidase activity accompanying tension wood differentiation and propose a testable hypothesis that such activity might regulate galactan entrapment and, thus, mechanical properties of cell walls in tension wood. PMID- 26378098 TI - Modifications of Sphingolipid Content Affect Tolerance to Hemibiotrophic and Necrotrophic Pathogens by Modulating Plant Defense Responses in Arabidopsis. AB - Sphingolipids are emerging as second messengers in programmed cell death and plant defense mechanisms. However, their role in plant defense is far from being understood, especially against necrotrophic pathogens. Sphingolipidomics and plant defense responses during pathogenic infection were evaluated in the mutant of long-chain base phosphate (LCB-P) lyase, encoded by the dihydrosphingosine-1 phosphate lyase1 (AtDPL1) gene and regulating long-chain base/LCB-P homeostasis. Atdpl1 mutants exhibit tolerance to the necrotrophic fungus Botrytis cinerea but susceptibility to the hemibiotrophic bacterium Pseudomonas syringae pv tomato (Pst). Here, a direct comparison of sphingolipid profiles in Arabidopsis (Arabidopsis thaliana) during infection with pathogens differing in lifestyles is described. In contrast to long-chain bases (dihydrosphingosine [d18:0] and 4,8 sphingadienine [d18:2]), hydroxyceramide and LCB-P (phytosphingosine-1-phosphate [t18:0-P] and 4-hydroxy-8-sphingenine-1-phosphate [t18:1-P]) levels are higher in Atdpl1-1 than in wild-type plants in response to B. cinerea. Following Pst infection, t18:0-P accumulates more strongly in Atdpl1-1 than in wild-type plants. Moreover, d18:0 and t18:0-P appear as key players in Pst- and B. cinerea induced cell death and reactive oxygen species accumulation. Salicylic acid levels are similar in both types of plants, independent of the pathogen. In addition, salicylic acid-dependent gene expression is similar in both types of B. cinerea-infected plants but is repressed in Atdpl1-1 after treatment with Pst. Infection with both pathogens triggers higher jasmonic acid, jasmonoyl-isoleucine accumulation, and jasmonic acid-dependent gene expression in Atdpl1-1 mutants. Our results demonstrate that sphingolipids play an important role in plant defense, especially toward necrotrophic pathogens, and highlight a novel connection between the jasmonate signaling pathway, cell death, and sphingolipids. PMID- 26378100 TI - Dynamic Maize Responses to Aphid Feeding Are Revealed by a Time Series of Transcriptomic and Metabolomic Assays. AB - As a response to insect attack, maize (Zea mays) has inducible defenses that involve large changes in gene expression and metabolism. Piercing/sucking insects such as corn leaf aphid (Rhopalosiphum maidis) cause direct damage by acquiring phloem nutrients as well as indirect damage through the transmission of plant viruses. To elucidate the metabolic processes and gene expression changes involved in maize responses to aphid attack, leaves of inbred line B73 were infested with corn leaf aphids for 2 to 96 h. Analysis of infested maize leaves showed two distinct response phases, with the most significant transcriptional and metabolic changes occurring in the first few hours after the initiation of aphid feeding. After 4 d, both gene expression and metabolite profiles of aphid infested maize reverted to being more similar to those of control plants. Although there was a predominant effect of salicylic acid regulation, gene expression changes also indicated prolonged induction of oxylipins, although not necessarily jasmonic acid, in aphid-infested maize. The role of specific metabolic pathways was confirmed using Dissociator transposon insertions in maize inbred line W22. Mutations in three benzoxazinoid biosynthesis genes, Bx1, Bx2, and Bx6, increased aphid reproduction. In contrast, progeny production was greatly decreased by a transposon insertion in the single W22 homolog of the previously uncharacterized B73 terpene synthases TPS2 and TPS3. Together, these results show that maize leaves shift to implementation of physical and chemical defenses within hours after the initiation of aphid feeding and that the production of specific metabolites can have major effects in maize-aphid interactions. PMID- 26378101 TI - Alteration of Plant Primary Metabolism in Response to Insect Herbivory. AB - Plants in nature, which are continuously challenged by diverse insect herbivores, produce constitutive and inducible defenses to reduce insect damage and preserve their own fitness. In addition to inducing pathways that are directly responsible for the production of toxic and deterrent compounds, insect herbivory causes numerous changes in plant primary metabolism. Whereas the functions of defensive metabolites such as alkaloids, terpenes, and glucosinolates have been studied extensively, the fitness benefits of changes in photosynthesis, carbon transport, and nitrogen allocation remain less well understood. Adding to the complexity of the observed responses, the feeding habits of different insect herbivores can significantly influence the induced changes in plant primary metabolism. In this review, we summarize experimental data addressing the significance of insect feeding habits, as related to herbivore-induced changes in plant primary metabolism. Where possible, we link these physiological changes with current understanding of their underlying molecular mechanisms. Finally, we discuss the potential fitness benefits that host plants receive from altering their primary metabolism in response to insect herbivory. PMID- 26378104 TI - Special feature on automatism. PMID- 26378102 TI - Grapevine and Arabidopsis Cation-Chloride Cotransporters Localize to the Golgi and Trans-Golgi Network and Indirectly Influence Long-Distance Ion Transport and Plant Salt Tolerance. AB - Plant cation-chloride cotransporters (CCCs) have been implicated in conferring salt tolerance. They are predicted to improve shoot salt exclusion by directly catalyzing the retrieval of sodium (Na(+)) and chloride (Cl(-)) ions from the root xylem. We investigated whether grapevine (Vitis vinifera [Vvi]) CCC has a role in salt tolerance by cloning and functionally characterizing the gene from the cultivar Cabernet Sauvignon. Amino acid sequence analysis revealed that VviCCC shares a high degree of similarity with other plant CCCs. A VviCCC-yellow fluorescent protein translational fusion protein localized to the Golgi and the trans-Golgi network and not the plasma membrane when expressed transiently in tobacco (Nicotiana benthamiana) leaves and Arabidopsis (Arabidopsis thaliana) mesophyll protoplasts. AtCCC-green fluorescent protein from Arabidopsis also localized to the Golgi and the trans-Golgi network. In Xenopus laevis oocytes, VviCCC targeted to the plasma membrane, where it catalyzed bumetanide-sensitive (36)Cl(-), (22)Na(+), and (86)Rb(+) uptake, suggesting that VviCCC (like AtCCC) belongs to the Na(+)-K(+)-2Cl(-) cotransporter class of CCCs. Expression of VviCCC in an Arabidopsis ccc knockout mutant abolished the mutant's stunted growth phenotypes and reduced shoot Cl(-) and Na(+) content to wild-type levels after growing plants in 50 mm NaCl. In grapevine roots, VviCCC transcript abundance was not regulated by Cl(-) treatment and was present at similar levels in both the root stele and cortex of three Vitis spp. genotypes that exhibit differential shoot salt exclusion. Our findings indicate that CCC function is conserved between grapevine and Arabidopsis, but neither protein is likely to directly mediate ion transfer with the xylem or have a direct role in salt tolerance. PMID- 26378105 TI - An anatomy of automatism. AB - The automatism defence has been described as a quagmire of law and as presenting an intractable problem. Why is this so? This paper will analyse and explore the current legal position on automatism. In so doing, it will identify the problems which the case law has created, including the distinction between sane and insane automatism and the status of the 'external factor doctrine', and comment briefly on recent reform proposals. PMID- 26378103 TI - The Arabidopsis Transcription Factor MYB112 Promotes Anthocyanin Formation during Salinity and under High Light Stress. AB - MYB transcription factors (TFs) are important regulators of flavonoid biosynthesis in plants. Here, we report MYB112 as a formerly unknown regulator of anthocyanin accumulation in Arabidopsis (Arabidopsis thaliana). Expression profiling after chemically induced overexpression of MYB112 identified 28 up- and 28 down-regulated genes 5 h after inducer treatment, including MYB7 and MYB32, which are both induced. In addition, upon extended induction, MYB112 also positively affects the expression of PRODUCTION OF ANTHOCYANIN PIGMENT1, a key TF of anthocyanin biosynthesis, but acts negatively toward MYB12 and MYB111, which both control flavonol biosynthesis. MYB112 binds to an 8-bp DNA fragment containing the core sequence (A/T/G)(A/C)CC(A/T)(A/G/T)(A/C)(T/C). By electrophoretic mobility shift assay and chromatin immunoprecipitation coupled to quantitative polymerase chain reaction, we show that MYB112 binds in vitro and in vivo to MYB7 and MYB32 promoters, revealing them as direct downstream target genes. We further show that MYB112 expression is up-regulated by salinity and high light stress, environmental parameters that both require the MYB112 TF for anthocyanin accumulation under these stresses. In contrast to several other MYB TFs affecting anthocyanin biosynthesis, MYB112 expression is not controlled by nitrogen limitation or an excess of carbon. Thus, MYB112 constitutes a regulator that promotes anthocyanin accumulation under abiotic stress conditions. PMID- 26378106 TI - The Law Commission's proposals for the reform of the defences of insanity and automatism. AB - The article offers an overview of the Law Commission's project on Insanity and Automatism and the provisional conclusions reached in its Discussion Paper in 2013. PMID- 26378107 TI - Reforming automatism and insanity: Neuroscience and claims of lack of capacity for control. AB - This paper examines some of the issues raised by the current criminal law defence of automatism and the related defence of insane automatism, and considers what neuroscience may contribute to the reform discussion. It also considers some of the claims made in relation to the impact of neuroimaging in the courtroom. It examines an American medical case report in which an individual's criminal behaviour is linked to a brain tumour, and considers how the reformed law as presented in the Law Commission for England and Wales' Discussion Paper might treat such claims. It concludes by examining what assistance the law may gain from a deeper understanding of how a sense of agency emerges from brain states, and the implications of this scientific knowledge for the reform of the law. PMID- 26378108 TI - Medico-legal evaluation of sleep-related automatism. PMID- 26378109 TI - Sleep in a legal context: The role of the expert witness. AB - Sleep experts are called to assist the jury in deciding the mental state of the accused at the time of their alleged criminal behaviour. This task is difficult as the literature on many sleep disorders, particularly sleepwalking and other parasomnias, is still largely a matter of case reports and case series. The probative value of much of the evidence given is not known. Sleep behaviour in the courts present a number of difficulties which illustrate the dilemmas that face an expert witness faced with ambiguous data and uncertain principles with which to interpret them. Additionally there are substantial policy issues involved which are not always adequately addressed in expert evidence. We outline the role of expert witnesses in such cases. PMID- 26378110 TI - Hypoglycaemia and automatism. AB - Cognitive impairment unattended by subjective symptoms or objective signs is an uncommon but important consequence of hypoglycaemia. It can lead to a condition in which a patient behaves as an automaton in a manner totally alien to their usual personality and of which they have no recollection when their blood glucose level is restored to normal. It can cause a wide range of criminal behaviour, although the commonest offences relate to a loss of control, for example driving offences. Determination of criminal responsibility is extremely difficult and relies very heavily upon the quality of the medical evidence and interpretation of the law, which is out of step with current medical science. PMID- 26378112 TI - The value of educational records for expert psychiatrists preparing medico-legal reports for children, adolescents and adults. PMID- 26378116 TI - Intergenerational Transmission of Marital Violence: Results From a Nationally Representative Sample of Men. AB - The present study assesses the association between childhood exposure to parental violence and perpetration of marital violence as adults among a representative sample of 3,396 men in Bangladesh. We used secondary analysis of survey data from the nationally representative Bangladesh Demographic and Health Survey 2007 to examine factors associated with perpetration of martial violence among 3,396 ever married men between the ages of 16 and 50 years. Outcome measure, marital violence perpetration, was measured using a modified Conflict Tactics Scale, and predictor variables included childhood exposure to parental violence, justification of marital violence, marital duration, religion, and demographic variables. Results indicate that marital violence perpetration is significantly associated with childhood exposure to marital violence, suggesting a cycle of violence that is maintained across generations. Implications for policy and practice are discussed. PMID- 26378117 TI - Identification of a pathogenic FTO mutation by next-generation sequencing in a newborn with growth retardation and developmental delay. AB - BACKGROUND: A homozygous loss-of-function mutation p.(Arg316Gln) in the fat mass and obesity-associated (FTO) gene, which encodes for an iron and 2-oxoglutarate dependent oxygenase, was previously identified in a large family in which nine affected individuals present with a lethal syndrome characterised by growth retardation and multiple malformations. To date, no other pathogenic mutation in FTO has been identified as a cause of multiple congenital malformations. METHODS: We investigated a 21-month-old girl who presented distinctive facial features, failure to thrive, global developmental delay, left ventricular cardiac hypertrophy, reduced vision and bilateral hearing loss. We performed targeted next-generation sequencing of 4813 clinically relevant genes in the patient and her parents. RESULTS: We identified a novel FTO homozygous missense mutation (c.956C>T; p.(Ser319Phe)) in the affected individual. This mutation affects a highly conserved residue located in the same functional domain as the previously characterised mutation p.(Arg316Gln). Biochemical studies reveal that p.(Ser319Phe) FTO has reduced 2-oxoglutarate turnover and N-methyl-nucleoside demethylase activity. CONCLUSION: Our findings are consistent with previous reports that homozygous mutations in FTO can lead to rare growth retardation and developmental delay syndrome, and further support the proposal that FTO plays an important role in early development of human central nervous and cardiovascular systems. PMID- 26378118 TI - Parenteral MCT/omega-3 Polyunsaturated Fatty Acid-Enriched Intravenous Fat Emulsion Is Associated With Cytokine and Fatty Acid Profiles Consistent With Attenuated Inflammatory Response in Preterm Neonates: A Randomized, Double-Blind Clinical Trial. AB - BACKGROUND: Soybean oil-based intravenous fat emulsion (IVFE) administered to preterm neonates can induce oxidative stress and inflammatory response, which are associated with severe complications of prematurity. This study aimed to test the hypothesis that administration of medium-chain triglyceride (MCT)/omega-3 polyunsaturated fatty acid (PUFA)-enriched IVFE in preterm neonates is associated with a cytokine and fatty acid (FA) profile consistent with attenuated inflammatory response. PATIENTS/METHODS: In a double-blind randomized study, 60 preterm neonates (gestational age 26-32 weeks) were randomized to receive either MCT/omega-3 PUFA-enriched IVFE (intervention group) or soybean oil-based IVFE (control group). Serum biochemistry, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-8, alpha-tocopherol, and FAs were assessed at baseline, on day of life 15, and day of life 30 or at the end of intervention. RESULTS: All cytokine levels changed significantly across the 3 time points, whereas the type of IVFE had a significant effect on final IL-6 and IL-8 levels, which were lower in the intervention group. The difference in final IL-6 and IL-8 levels remained significant after controlling for bronchopulmonary dysplasia and/or infection. alpha-Tocopherol and FA values changed significantly over time. MCT/omega-3 PUFA enriched IVFE administration was associated with significantly higher alpha tocopherol, eicosapentaenoic acid, docosahexaenoic acid, and omega-3 PUFAs and lower linolenic acid, total PUFA, and omega-6/omega-3 PUFA values compared with soybean oil-based IVFE. Both IVFEs were well tolerated. CONCLUSION: Compared with the soybean oil-based IVFE, the MCT/omega-3 PUFA-enriched IVFE is associated with a more favorable cytokine and FA profile consistent with attenuated inflammatory response in preterm neonates. PMID- 26378119 TI - A self-regulating biomolecular comparator for processing oscillatory signals. AB - While many cellular processes are driven by biomolecular oscillators, precise control of a downstream on/off process by a biochemical oscillator signal can be difficult: over an oscillator's period, its output signal varies continuously between its amplitude limits and spends a significant fraction of the time at intermediate values between these limits. Further, the oscillator's output is often noisy, with particularly large variations in the amplitude. In electronic systems, an oscillating signal is generally processed by a downstream device such as a comparator that converts a potentially noisy oscillatory input into a square wave output that is predominantly in one of two well-defined on and off states. The comparator's output then controls downstream processes. We describe a method for constructing a synthetic biochemical device that likewise produces a square wave-type biomolecular output for a variety of oscillatory inputs. The method relies on a separation of time scales between the slow rate of production of an oscillatory signal molecule and the fast rates of intermolecular binding and conformational changes. We show how to control the characteristics of the output by varying the concentrations of the species and the reaction rates. We then use this control to show how our approach could be applied to process different in vitro and in vivo biomolecular oscillators, including the p53-Mdm2 transcriptional oscillator and two types of in vitro transcriptional oscillators. These results demonstrate how modular biomolecular circuits could, in principle, be combined to build complex dynamical systems. The simplicity of our approach also suggests that natural molecular circuits may process some biomolecular oscillator outputs before they are applied downstream. PMID- 26378120 TI - Biocompatibility, degradability, bioactivity and osteogenesis of mesoporous/macroporous scaffolds of mesoporous diopside/poly(L-lactide) composite. AB - Bioactive mesoporous diopside (m-DP) and poly(L-lactide) (PLLA) composite scaffolds with mesoporous/macroporous structure were prepared by the solution casting and particulate-leaching method. The results demonstrated that the degradability and bioactivity of the mesoporous/macroporous scaffolds were significantly improved by incorporating m-DP into PLLA, and that the improvement was m-DP content-dependent. In addition, the scaffolds containing m-DP showed the ability to neutralize acidic degradation products and prevent the pH from dropping in the solution during the soaking period. Moreover, the scaffolds containing m-DP enhanced attachment, proliferation and alkaline phosphatase activity of MC3T3-E1 cells, which were also m-DP content-dependent. Furthermore, the histological and immunohistochemical analysis results showed that the scaffolds with m-DP significantly promoted new bone formation and improved the materials degraded in vivo, indicating good biocompatibility. The results suggested that the mesoporous/macroporous scaffolds of the m-DP/PLLA composite with osteogenesis had a potential for bone regeneration. PMID- 26378121 TI - A frequency-based hypothesis for mechanically targeting and selectively attacking cancer cells. AB - Experimental studies recently performed on single cancer and healthy cells have demonstrated that the former are about 70% softer than the latter, regardless of the cell lines and the measurement technique used for determining the mechanical properties. At least in principle, the difference in cell stiffness might thus be exploited to create mechanical-based targeting strategies for discriminating neoplastic transformations within human cell populations and for designing innovative complementary tools to cell-specific molecular tumour markers, leading to possible applications in the diagnosis and treatment of cancer diseases. With the aim of characterizing and gaining insight into the overall frequency response of single-cell systems to mechanical stimuli (typically low-intensity therapeutic ultrasound), a generalized viscoelastic paradigm, combining classical and spring pot-based models, is introduced for modelling this problem by neglecting the cascade of mechanobiological events involving the cell nucleus, cytoskeleton, elastic membrane and cytosol. Theoretical results show that differences in stiffness, experimentally observed ex vivo and in vitro, allow healthy and cancer cells to be discriminated, by highlighting frequencies (from tens to hundreds of kilohertz) associated with resonance-like phenomena-prevailing on thermal fluctuations-that could be helpful in targeting and selectively attacking tumour cells. PMID- 26378122 TI - Antipsychotic-induced metabolic effects in the female rat: Direct comparison between long-acting injections of risperidone and olanzapine. AB - Several antipsychotics have well-known adverse metabolic effects. Studies uncovering molecular mechanisms of such drugs in patients are challenging due to high dropout rates, previous use of antipsychotics and restricted availability of biological samples. Rat experiments, where previously unexposed animals are treated with antipsychotics, allow for direct comparison of different drugs, but have been hampered by the short half-life of antipsychotics in rodents. The use of long-acting formulations of antipsychotics could significantly increase the value of rodent models in the molecular characterization of therapeutic and adverse effects of these agents. However, as long-acting formulations have rarely been used in rodents, there is a need to characterize the basic metabolic phenotype of different antipsychotics. Using long-acting olanzapine injections as a positive control, the metabolic effects of intramuscular long-acting risperidone in female rats were investigated for the first time. Like olanzapine, risperidone induced rapid, significant hyperphagia and weight gain, with concomitant increase in several plasma lipid species. Both drugs also induced weight-independent upregulation of several genes encoding enzymes involved in lipogenesis, but this activation was not confirmed at the protein level. Our findings shed light on the role of drug administration, drug dose and nutritional status in the development of rodent models for adverse metabolic effects of antipsychotic agents. PMID- 26378123 TI - Health care professionals' perspectives of advance care planning for people with dementia living in long-term care settings: A narrative review of the literature. AB - This paper provides an overview of the evidence on the perspective of health care professionals (HCPs) in relation to advance care planning (ACP) for people with dementia, residing in long-term care settings. A narrative approach was adopted to provide a comprehensive synthesis of previously published literature in the area. A systematic literature search identified 14 papers for inclusion. Following review of the studies four themes were identified for discussion; Early integration and planning for palliative care in dementia; HCPs ethical and moral concerns regarding ACP; Communication challenges when interacting with the person with dementia and their families and HCPs need for education and training. Despite evidence, that HCPs recognise the potential benefits of ACP, they struggle with its implementation in this setting. Greater understanding of dementia and the concept of ACP is required to improve consistency in practice. Synthesising the existing evidence will allow for further understanding of the key issues, potentially resulting in improved implementation in practice. PMID- 26378124 TI - 'This is my story, how I remember it': In-depth analysis of Dignity Therapy documents from a study of Dignity Therapy for people with early stage dementia. AB - Dementia is a progressive condition that impacts on individuals, families and care professionals. Maintaining quality of life through engagement with the person with dementia is an important part of their care. Dignity Therapy is an interactive, psychotherapeutic intervention that uses a trained dignity therapist to guide the person with dementia through an interview that then creates a written legacy called a generativity document. This can provide knowledge to inform care, as the condition progresses. Generativity documents were analysed using framework analysis. Main themes from the analysis were origin of values, essence and affirmation of self, forgiveness and resolution and existentialism/ meaning of life. These themes provide evidence of the type, scope and contribution that information generated from Dignity Therapy can make to the care and support of people with dementia. They provide information about the values, self-identity and the people and events that have been important to them and influenced their lives. PMID- 26378125 TI - Risks in situations that are experienced as unfamiliar and confusing - the perspective of persons with dementia. AB - An increasing number of people with dementia are ageing at home in Sweden and in other countries. In order to meet the safety requirements, knowledge about how persons with dementia experience risks is required. The aim of the study was to explore and better understand how persons with dementia, living at home, experience risks in their daily life and how they handle these situations. Twelve persons with dementia were interviewed using open-ended questions, and the data were analyzed using a content analysis approach. Findings showed that participants experienced situations fraught with risks in their daily life as unfamiliar and confusing. Previously familiar places became unfamiliar to them, and details did not come together. They were uncertain about what actually had happened. How the participants handled these situations in order to reduce the risks are described. PMID- 26378126 TI - Assembly of the unusual oxacycles in the orthosomycin antibiotics. PMID- 26378127 TI - Receptor-like cytoplasmic kinase MARIS functions downstream of CrRLK1L-dependent signaling during tip growth. AB - Growing plant cells need to rigorously coordinate external signals with internal processes. For instance, the maintenance of cell wall (CW) integrity requires the coordination of CW sensing with CW remodeling and biosynthesis to avoid growth arrest or integrity loss. Despite the involvement of receptor-like kinases (RLKs) of the Catharanthus roseus RLK1-like (CrRLK1L) subfamily and the reactive oxygen species-producing NADPH oxidases, it remains largely unknown how this coordination is achieved. ANXUR1 (ANX1) and ANX2, two redundant members of the CrRLK1L subfamily, are required for tip growth of the pollen tube (PT), and their closest homolog, FERONIA, controls root-hair tip growth. Previously, we showed that ANX1 overexpression mildly inhibits PT growth by oversecretion of CW material, whereas pollen tubes of anx1 anx2 double mutants burst spontaneously after germination. Here, we report the identification of suppressor mutants with improved fertility caused by the rescue of anx1 anx2 pollen tube bursting. Mapping of one these mutants revealed an R240C nonsynonymous substitution in the activation loop of a receptor-like cytoplasmic kinase (RLCK), which we named MARIS (MRI). We show that MRI is a plasma membrane-localized member of the RLCK VIII subfamily and is preferentially expressed in both PTs and root hairs. Interestingly, mri-knockout mutants display spontaneous PT and root-hair bursting. Moreover, expression of the MRI(R240C) mutant, but not its wild-type form, partially rescues the bursting phenotypes of anx1 anx2 PTs and fer root hairs but strongly inhibits wild-type tip growth. Thus, our findings identify a novel positive component of the CrRLK1L-dependent signaling cascade that coordinates CW integrity and tip growth. PMID- 26378129 TI - Tendon Graft Healing in Multiligament Reconstructed Knee Detected by FDG-PET/CT: A Pilot Study. AB - BACKGROUND AND AIMS: The detection of graft viability is challenging in the multiligament reconstructed knee. Magnetic resonance imaging gives structural information but lacks the capability to assess biological activity of the grafts. (18)F-labeled fluorodeoxyglucose positron emission tomography combined with computer tomography is shown to be a sensitive method for imaging tissue metabolism and viability. The aim of the present study was to evaluate the feasibility of fluorodeoxyglucose positron emission tomography combined with computer tomography imaging in the detection of the replacement graft metabolism in multiligament reconstructed knees. MATERIALS AND METHODS: Seven patients (17 44 years) with multiligament reconstructed knee underwent fluorodeoxyglucose positron emission tomography combined with computer tomography to evaluate the biological activity of replacement grafts. The degree of fluorodeoxyglucose uptake reported as standard uptake values from the region of interest was analyzed 3-24 months postoperatively. RESULTS: In all patients, the fluorodeoxyglucose positron emission tomography combined with computer tomography showed increased fluorodeoxyglucose uptake in all replacement grafts at different follow-up time points. Furthermore, fluorodeoxyglucose was higher at femoral condyles of operated knees compared to contralateral reference values. CONCLUSION: This pilot study shows a significant increase in tendon graft metabolism during two first years of postoperative healing. The fluorodeoxyglucose positron emission tomography combined with computer tomography imaging seems to be adequate method of assessment of graft metabolism and viability during postoperative healing. The clinical value of fluorodeoxyglucose positron emission tomography combined with computer tomography imaging, however, warrants further evaluation with longitudinal studies with a larger patient population. PMID- 26378128 TI - Viscosity of deeply supercooled water and its coupling to molecular diffusion. AB - The viscosity of a liquid measures its resistance to flow, with consequences for hydraulic machinery, locomotion of microorganisms, and flow of blood in vessels and sap in trees. Viscosity increases dramatically upon cooling, until dynamical arrest when a glassy state is reached. Water is a notoriously poor glassformer, and the supercooled liquid crystallizes easily, making the measurement of its viscosity a challenging task. Here we report viscosity of water supercooled close to the limit of homogeneous crystallization. Our values contradict earlier data. A single power law reproduces the 50-fold variation of viscosity up to the boiling point. Our results allow us to test the Stokes-Einstein and Stokes Einstein-Debye relations that link viscosity, a macroscopic property, to the molecular translational and rotational diffusion, respectively. In molecular glassformers or liquid metals, the violation of the Stokes-Einstein relation signals the onset of spatially heterogeneous dynamics and collective motions. Although the viscosity of water strongly decouples from translational motion, a scaling with rotational motion remains, similar to canonical glassformers. PMID- 26378130 TI - Tibial Fractures in Alpine Skiing and Snowboarding in Finland: A Retrospective Study on Fracture Types and Injury Mechanisms in 363 Patients. AB - BACKGROUND AND AIM: Alpine skiing and snowboarding share the hazards of accidents accounting for tibial fractures. The aim of this study was to evaluate the fracture patterns and mechanisms of injury of tibial fractures taking place in downhill skiing and snowboarding. MATERIALS AND METHODS: All patients with tibial fracture due to alpine skiing or snowboarding accident treated in four trauma centers next to the largest ski resorts in Finland were analyzed between 2006 and 2012. The hospital records were retrospectively reviewed for data collection: equipment used (skis or snowboard), age, gender, and mechanism of injury. Fractures were classified according to AO-classification. RESULTS: There were 342 skiing and 30 snowboarding related tibial fractures in 363 patients. Tibial shaft fracture was the most common fracture among skiers (n = 215, 63%), followed by proximal tibial fractures (n = 92, 27%). Snowboarders were most likely to suffer from proximal tibial fracture (13, 43%) or tibial shaft fracture (11, 37%). Snowboarders were also more likely than skiers to suffer complex AO type C fractures (23% vs 9%, p < 0.05). Adult skiers had both wider variety of fractures and higher prevalence of proximal tibial fractures compared to children (49% vs 16%, p < 0.05). Skiers typically got injured due to falling down on the same level (70%) and snowboarders due to loss of control while jumping (46%). CONCLUSION: The most important finding was the relatively high number of the tibial plateau fractures among adult skiers. The fracture patterns between snowboarding and skiing were different; the most common fracture type in skiers was spiral tibial shaft fracture compared to proximal tibial fractures in snowboarders. Children had more simple fractures than adults. PMID- 26378132 TI - Driving Under the Influence of Marijuana Versus Driving and Dying Under the Influence of Marijuana: A Comparison of Blood Concentrations of Delta9 Tetrahydrocannabinol, 11-Hydroxy-Delta9-Tetrahydrocannabinol, 11-Nor-9-Carboxy Delta9-Tetrahydrocannabinol and Other Cannabinoids in Arrested Drivers Versus Deceased Drivers. AB - Cannabis intoxication in living and deceased drivers is an important medico-legal topic, but only a limited number of studies examine cannabinoids in living and deceased humans. This study compares cannabinoid concentrations (in ng/mL) in driving under the influence of drug (DUID) drivers with blood cannabinoids to those in drivers who died while driving with cannabinoids in their postmortem (PM) peripheral blood. From 2010 to 2013, there were 318 cannabis-positive DUID cases (mean, median THC: 4.9, 3); 88 had cannabis-only in their bloods (mean, median THC: 5.8, 4). In 23 DUID cases, Huestis' Predictive Models with 95% confidence intervals were applied and evaluated, demonstrating that the actual case time points in all 23 cases fell within the predicted time ranges. Among deceased drivers, 19 had cannabis-positive toxicology (mean, median THC: 11.7, 4.5) and 8 had cannabis-only (mean, median THC: 20.3, 19.5). Motorcyclists and bicyclists comprised the majority of deceased vehicle operators, with bicyclists averaging the highest mean and median THC concentrations overall. The analysis of variance between living and deceased drivers' cannabinoid concentrations showed that THC-OH and THC-COOH concentrations are not statistically different between the two groups, but that THC concentrations are statistically different, making it difficult to directly correlate PM with antemortem THC concentrations between living and deceased drivers. PMID- 26378131 TI - Plasma Cannabinoid Pharmacokinetics After Controlled Smoking and Ad libitum Cannabis Smoking in Chronic Frequent Users. AB - More Americans are dependent on cannabis than any other illicit drug. The main analytes for cannabis testing include the primary psychoactive constituent, Delta(9)-tetrahydrocannabinol (THC), equipotent 11-hydroxy-THC (11-OH-THC) and inactive 11-nor-9-carboxy-THC (THCCOOH). Eleven adult chronic frequent cannabis smokers resided on a closed research unit with unlimited access to 5.9% THC cannabis cigarettes from 12:00 to 23:00 during two ad libitum smoking phases, followed by a 5-day abstinence period in seven participants. A single cigarette was smoked under controlled topography on the last day of the smoking and abstinence phases. Plasma cannabinoids were quantified by two-dimensional gas chromatography-mass spectrometry. Median plasma maximum concentrations (Cmax) were 28.3 (THC), 3.9 (11-OH-THC) and 47.0 MUg/L (THCCOOH) 0.5 h after controlled single cannabis smoking. Median Cmax 0.2-0.5 h after ad libitum smoking was higher for all analytes: 83.5 (THC), 14.2 (11-OH-THC) and 155 MUg/L (THCCOOH). All 11 participants' plasma samples were THC and THCCOOH-positive, 58.3% had THC >=5 MUg/L and 79.2% were 11-OH-THC-positive 8.1-14 h after last cannabis smoking. Cannabinoid detection rates in seven participants 106-112 h (4-5 days) after last smoking were 92.9 (THC), 35.7 (11-OH-THC) and 100% (THCCOOH), with limits of quantification of 0.5 MUg/L for THC and THCCOOH, and 1.0 MUg/L for 11-OH-THC. These data greatly expand prior research findings on cannabinoid excretion profiles in chronic frequent cannabis smokers during ad libitum smoking. Smoking multiple cannabis cigarettes led to higher Cmax and AUC compared with smoking a single cigarette. The chronic frequent cannabis smokers exhibited extended detection windows for plasma cannabinoids, reflecting a large cannabinoid body burden. PMID- 26378133 TI - Fatal Intoxications with 25B-NBOMe and 25I-NBOMe in Indiana During 2014. AB - Over the last few years, NBOMe substances have been used either as a legal alternative to lysergic acid diethylamide (LSD) or sold surreptitiously as LSD to unknown users. These NBOMe substances have been detected in blotter papers, powders, capsules and liquids. We report the deaths of two teenage male subjects that were related to 25B-NBOMe and 25I-NBOMe in Indiana during 2014. Samples were extracted via a solvent protein precipitation with acetonitrile and analyzed via ultra-performance liquid chromatography with tandem mass spectrometry. For these two cases, we describe the NBOMe instrumental analysis, toxicological results for postmortem heart blood and urine specimens and the relevant case history and pathological findings at autopsy. In the first case, 25B-NBOMe was detected in postmortem heart blood at 1.59 ng/mL; in the second case, 25I-NBOMe was detected in postmortem heart blood at 19.8 ng/mL. We also review relevant published casework from clinical toxicology and postmortem toxicology in which analytically confirmed 25B-NBOMe and 25I-NBOMe were determined to be causative agents in intoxications or deaths. PMID- 26378134 TI - Identification of Metabolite Biomarkers of the Designer Hallucinogen 25I-NBOMe in Mouse Hepatic Microsomal Preparations and Human Urine Samples Associated with Clinical Intoxication. AB - 'NBOMe' (dimethoxyphenyl-N-[(2-methoxyphenyl)methyl]ethanamine) derivatives are a new class of designer hallucinogenic drugs widely available on the Internet. Currently, 2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine (25I-NBOMe) is the most popular abused derivative in the USA. There are little published data on the absorption, metabolism and elimination of 25I-NBOMe, or any of the other NBOMe derivatives. Therefore, there are no definitive metabolite biomarkers. We present the identification of fifteen 25I-NBOMe metabolites in phase I and II mouse hepatic microsomal preparations, and analysis of two human urine samples from 25I-NBOMe-intoxicated patients to test the utility of these metabolites as biomarkers of 25I-NBOMe use. The synthesis of two major urinary metabolites, 2-iodo-4-methoxy-5-[2-[(2-methoxyphenyl) methylamino]ethyl]phenol (2 O-desmethyl-5-I-NBOMe, M5) and 5-iodo-4-methoxy-2-[2-[(2 methoxyphenyl)methylamino]ethyl]phenol (5-O-desmethyl-2-I-NBOMe), is also presented. Seven phase II glucuronidated metabolites of the O-desmethyl or the hydroxylated phase I metabolites were identified. One human urine sample contained 25I-NBOMe as well as all 15 metabolites identified in mouse hepatic microsomal preparations. Another human urine sample contained no parent 25I NBOMe, but was found to contain three O-desmethyl metabolites. We recommend beta glucuronidase enzymatic hydrolysis of urine prior to 25I-NBOMe screening and the use of M5 as the primary biomarker in drug testing. PMID- 26378135 TI - Analysis of 25I-NBOMe, 25B-NBOMe, 25C-NBOMe and Other Dimethoxyphenyl-N-[(2 Methoxyphenyl) Methyl]Ethanamine Derivatives on Blotter Paper. AB - In recent years, N-methoxybenzyl-methoxyphenylethylamine (NBOMe) derivatives, a class of designer hallucinogenic drugs, have become popular drugs of abuse. These drugs have been the cause of severe intoxications and even deaths. They act as 5 HT2A receptors agonists and have been reported to produce serotonin-like syndrome with bizarre behavior, severe agitation and seizures persisting for as long as 3 days. The most commonly reported derivatives are 25I-NBOMe, 25B-NBOMe and 25C NBOMe, respectively 2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl) methyl]ethanamine, N-(2-methoxybenzyl)-2,5-dimethoxy-4-bromophenethylamine and N (2-methoxybenzyl)-2,5-dimethoxy-4-chlorophenethylamine. Like many low dose hallucinogenic drugs these compounds are often sold on blotter paper. Three different types of commercially available blotter papers reported to contain NBOMe derivatives were obtained. These blotter papers were screened using Direct Analysis in Real Time AccuTOF(TM) mass spectrometry followed by confirmation and quantification by high-performance liquid chromatography triple quadrapole mass spectrometry. The major drug present on each of the three blotter products was different, 25I-NBOMe, 25C-NBOMe or 25B-NBOMe. The blotter papers were also found to have minute amounts of two or three NBOMe derivative impurities of 25H-NBOMe, 25I-NBOMe, 25C-NBOMe, 25B-NBOMe and/or 25D-NBOMe. PMID- 26378136 TI - Detection of Drugs in Nails: Three Year Experience. AB - Nails (fingernails and toenails) are made of keratin. As the nail grows, substances incorporate into the keratin fibers where they can be detected 3-6 months after use. Samples are collected by clipping of 2-3 mm of nail from all fingers (100 mg). We present drug testing results from 10,349 nail samples collected from high-risk cases during a 3-year period of time. Samples were analyzed by validated analytical methods. The initial testing was performed mostly using enzyme-linked immunosorbent assay, but by liquid chromatography tandem mass spectrometry (LC-MS-MS) as well. Presumptive positive samples were subjected to confirmatory testing with sample preparation procedures including washing, pulverizing, digestion and extraction optimized for each drug class. The total of 7,799 samples was analyzed for amphetamines. The concentrations ranged from 40 to 572,865 pg/mg (median, 100-3,687) for all amphetamine analytes. Amphetamine and methamphetamine were present in 14% of the samples, 22 samples were positive for 3,4-methylenedioxymethamphetamine (0.3%), 7 for methylenedioxyamphetamine (0.09%) and 4 for 3,4-methylenedioxy-N-ethylamphetamine (0.05%). Cocaine and related analytes were found in 5% samples (7,787 total), and the concentration range was 20-265,063 pg/mg (median 84-1,768). Opioids overall ranged from 40 to 118,229 pg/mg (median 123-830). The most prevalent opioid was oxycodone (15.1%) and hydrocodone (11.4%) compared with 1.0-3.6% for the others, including morphine, codeine, hydromorphone, methadone, 2-ethylidene-1,5-dimethyl 3,3-diphenylpyrrolidine and oxymorphone. Carboxy-Delta-9-tetrahydrocannabinol positivity rate was 18.1% (0.04-262 pg/mg, median 6.41). Out of 3,039 samples, 756 were positive (24.9%) for ethyl glucuronide (20-3,754 pg/mg, median 88). Other drugs found in nails included barbiturates, benzodiazepines, ketamine, meperidine, tramadol, zolpidem, propoxyphene, naltrexone and buprenorphine. Nail analyses have become a reliable way of determining the long-term use and abuse of drugs. Extraction techniques are simple and produce accurate and precise results. Sensitive analytical instrumentation, mainly LC-MS-MS, allows for detection of femtogram (10(-15) g) quantities of substances in nails. Samples were from a high risk population, therefore the extraordinary positivity rate was observed. PMID- 26378137 TI - Postmortem Metaxalone (Skelaxin(r)) Data from North Carolina. AB - The North Carolina Office of the Chief Medical Examiner Toxicology Laboratory identified 61 cases from 2002 to 2014 where metaxalone was detected during routine postmortem drug screening in support of a determination of cause and manner of death. Decedents were divided into groups based on the manner of death with the goal of studying metaxalone concentrations in overdose and non-overdose situations (natural, accident, suicide and undetermined). Subgroups were established for cases in which metaxalone contributed to the cause of death (attributed) and cases in which it did not (unattributed). Attributed cases were divided into those where metaxalone additively combined with other drugs and cases in which the drug was present in sufficient amounts to be the primary cause of death, regardless of other drugs present and the concentrations of those drugs. The mean metaxalone concentration for the additive deaths was 14.2 mg/L with a median value of 11 mg/L (n = 18) and a mean metaxalone concentration of 36.7 mg/L with a median value of 32 mg/L (n = 9) for primary deaths. For unattributed metaxalone concentrations, the mean was 3.4 mg/L with a median value of 2.9 mg/L (n = 31). Of the 61 cases, 34% fall at or below a therapeutic concentration of <=4 mg/L. The selected case studies offer valuable information regarding postmortem interpretation. PMID- 26378138 TI - Paroxetine in Postmortem Fluids and Tissues from Nine Aviation Accident Victims. AB - Paroxetine is a selective serotonin reuptake inhibitor commonly prescribed for the treatment of depression, obsessive-compulsive disorder, panic disorder, social anxiety disorder and post-traumatic stress disorder. While the use of paroxetine is considered relatively safe, negative side effects, including nausea, drowsiness, insomnia and dizziness, can adversely affect a pilot's ability to safely operate an aircraft. The use of paroxetine may increase suicidal behavior and suicidal ideation. When relying on postmortem specimens for toxicological evaluation, a general understanding of drug distribution throughout postmortem specimens is important. This laboratory has determined the distribution of paroxetine in postmortem tissues and fluids from nine aviation accident fatalities. Specimens were processed using an n-butyl chloride liquid/liquid extraction followed by gas chromatographic/mass spectrometeric analysis. Blood paroxetine concentrations obtained from these cases ranged from 0.019 to 0.865 ug/mL. The distribution of paroxetine, expressed as mean specimen/blood ratio, was 1.67 +/- 1.16 urine (n = 4), 0.08 +/- 0.04 vitreous humor (n = 6), 5.77 +/- 1.37 liver (n = 8), 9.66 +/- 2.58 lung (n = 9), 1.44 +/- 0.57 kidney (n = 8), 3.80 +/- 0.69 spleen (n = 8), 0.15 +/- 0.04 muscle (n = 8), 4.27 +/- 2.64 brain (n = 7) and 1.05 +/- 0.43 heart (n = 8). The large standard deviations associated with the paroxetine distribution coefficients suggest that paroxetine can experience significant postmortem concentration changes. PMID- 26378139 TI - Concentrations of AB-CHMINACA and AB-PINACA and Driving Behavior in Suspected Impaired Driving Cases. AB - This article reviews case reports for 58 suspected impaired driving cases that were positive for the synthetic cannabinoids AB-CHMINACA or AB-PINACA. All cases were submitted to the Washington State Patrol Toxicology Laboratory in 2014 from either Washington State or State of Alaska law enforcement agencies. The population of drivers was predominantly male (95%), with a mean age of 28 years (range, 18-61 years). The range of blood concentrations was 0.6->10 ng/mL for AB CHMINACA (N = 33) and 0.6-41.3 ng/mL for AB-PINACA (N = 25). Drug Recognition Expert exams were performed in 10 cases for each AB-CHMINACA and AB-PINACA. Horizontal gaze nystagmus was observed in 50 and 60% of the cases, respectively. Overall, several physiological indicators varied from those typically observed with marijuana use. The majority of these cases had very poor driving; subjects were involved in an accident, found passed out in a vehicle or were called in as a suspected impaired driver. Slurred speech, confusion, lack of coordination/dexterity and lethargy were commonly observed. PMID- 26378140 TI - Recovery and Stability of Delta9-Tetrahydrocannabinol Using the Oral-Eze(r) Oral Fluid Collection System and Intercept(r) Oral Specimen Collection Device. AB - Oral fluid (OF) is increasingly used for clinical, forensic and workplace drug testing as an alternative to urine. Uncertainties surrounding OF collection device performance, drug stability and testing reproducibility may be partially responsible for delays in the implementation of OF testing in regulated drug testing programs. Stability of Delta(9)-tetrahydrocannabinol (THC) fortified and authentic specimens was examined after routine collection, transport and laboratory testing. Acceptable recovery and stability were observed when THC fortified OF (1.5 and 4.5 ng/mL) was applied to Oral-Eze devices. Neat OF samples collected with Oral-Eze, processed per the package insert, and fortified with THC (3 and 6 ng/mL) were stable (+/-20%) at room temperature (21-25 degrees C), refrigerated (2-8 degrees C) and frozen (-25 to -15 degrees C) conditions up to 1 month, while samples collected with Intercept devices showed decreases at refrigerated and room temperatures. After long-term refrigerated or frozen storage, maximum reductions in THC concentrations were 42% for Oral-Eze and 69% for Intercept. After >=1 year frozen storage, 80.7% of laboratory specimens positive for THC (3 ng/mL cut-off) by GC-MS were reconfirmed positive (within 25%), with an average THC decrease of 4.2%. Specimens (n = 47) processed with Oral-Eze (diluted) and tested via enzyme immunoassay were concordant with LC-MS MS results and showed 100% sensitivity and 95% specificity. Paired specimens collected with Oral-Eze and Intercept exhibited 98% overall agreement between the immunoassay test systems. Collectively, these data demonstrate consistent and reproducible recovery and stability of THC in OF after collection, transport and laboratory testing using the Oral-Eze OF Collection System. PMID- 26378141 TI - Concentrations of Morphine and Codeine in Paired Oral Fluid and Urine Specimens Following Ingestion of a Poppy Seed Roll and Raw Poppy Seeds. AB - Interpretation of opiate drug test results can be challenging due to casual dietary consumption of poppy seeds, which may contain variable opiate content. Opiate concentrations in paired oral fluid (OF), collected with the Oral-Eze((r)) Oral Fluid Collection System, and urine were analyzed after ingestion of poppy seeds from the same source, consumed raw or contained in a roll. In Part 1, 12 individuals consumed equal portions of a poppy seed roll. For Part 2, the same individuals consumed an equivalent quantity of raw poppy seeds, containing ~3.2 mg of morphine and 0.6 mg of codeine. Specimens were analyzed both by enzyme immunoassay (opiates) and by GC-MS (morphine/codeine). Urinary morphine was between 155-1,408 (roll) and 294-4,213 ng/mL (raw), measured at 2, 4, 6 and 20 h post-ingestion. Urinary codeine concentrations between 140-194 (roll) and 121-664 ng/mL (raw) were observed up to 6 h post-ingestion. Following consumption of raw poppy seeds, OF specimens were positive, above LOQ, from 0.25 to 3.0 h with morphine ranging from 7 to 600 ng/mL and codeine from 8 to 112 ng/mL. After poppy seed roll consumption, morphine concentrations of 7-143 ng/mL were observed up to 1.5 h with codeine detected in only 5.5% of OF specimens and ranging from 8 to 28 ng/mL. Combined with the existing poppy seed literature, these results support previous findings and provide guidance for interpretation of OF opiate testing. PMID- 26378142 TI - A Dilute-and-Shoot LC-MS Method for Quantitating Opioids in Oral Fluid. AB - Opioid testing represents a dominant share of the market in pain management clinical testing facilities. Testing of this drug class in oral fluid (OF) has begun to rise in popularity. OF analysis has traditionally required extensive clean-up protocols and sample concentration, which can be avoided. This work highlights the use of a fast, 'dilute-and-shoot' method that performs no considerable sample manipulation. A quantitative method for the determination of eight common opioids and associated metabolites (codeine, morphine, hydrocodone, hydromorphone, norhydrocodone, oxycodone, noroxycodone and oxymorphone) in OF is described herein. OF sample is diluted 10-fold in methanol/water and then analyzed using an Agilent chromatographic stack coupled with an AB SCIEX 4500. The method has a 2.2-min LC gradient and a cycle time of 2.9 min. In contrast to most published methods of this particular type, this method uses no sample clean up or concentration and has a considerably faster LC gradient, making it ideal for very high-throughput laboratories. Importantly, the method requires only 100 MUL of sample and is diluted 10-fold prior to injection to help with instrument viability. Baseline separation of all isobaric opioids listed above was achieved on a phenyl-hexyl column. The validated calibration range for this method is 2.5 1,000 ng/mL. This 'dilute-and-shoot' method removes the unnecessary, costly and time-consuming extraction steps found in traditional methods and still surpasses all analytical requirements. PMID- 26378143 TI - A Case Review of the First Analytically Confirmed 25I-NBOMe-Related Death in Washington State. AB - This case was submitted to the Washington State Patrol Toxicology Laboratory in September 2014. A 15-year-old male went to a party where he ingested 25I-NBOMe and mushrooms. A short time later, he started to vomit and began seizing until he eventually passed out. Resuscitation efforts were made, but were unsuccessful. He was transported to a local hospital, where he died three days later of multi system organ failure following cardiopulmonary arrest. The hospital admission samples were negative for ethanol and basic drugs and their metabolites. The hospital serum confirmed positive for delta-9-tetrahydrocannabinol (THC) and carboxy-THC at 4.1 and 83 ng/mL, respectively. On the basis of the case history, the hospital blood and urine were sent to NMS Labs for NBOMe and psilocin confirmation. The blood was positive for 25I-NBOMe, and the urine was positive for 25C-, 25H- and 25I-NBOMe, as well as, psilocin. Antemortem and postmortem blood were also sent to AIT Laboratories for NBOMe confirmation. The antemortem blood confirmed positive for 25I-NBOMe with a concentration of 0.76 ng/mL. The manner of death was ruled an accident as a result of combined 25I-NBOMe and psilocin intoxication. PMID- 26378144 TI - The Impact of Hemolysis on the Accuracy of Ethanol Determinations. PMID- 26378150 TI - Characterization of a sialate-O-acetylesterase (NanS) from the oral pathogen Tannerella forsythia that enhances sialic acid release by NanH, its cognate sialidase. AB - Tannerella forsythia, a Gram-negative member of the Bacteroidetes has evolved to harvest and utilize sialic acid. The most common sialic acid in humans is a mono N-acetylated version termed Neu5Ac (5-N-acetyl-neuraminic acid). Many bacteria are known to access sialic acid using sialidase enzymes. However, in humans a high proportion of sialic acid contains a second acetyl group attached via an O group, i.e. chiefly O-acetylated Neu5,9Ac2 or Neu5,4Ac2. This diacetylated sialic acid is not cleaved efficiently by many sialidases and in order to access diacetylated sialic acid, some organisms produce sialate-O-acetylesterases that catalyse the removal of the second acetyl group. In the present study, we performed bioinformatic and biochemical characterization of a putative sialate-O acetylesterase from T. forsythia (NanS), which contains two putative SGNH hydrolase domains related to sialate-O-acetylesterases from a range of organisms. Purification of recombinant NanS revealed an esterase that has activity against Neu5,9Ac2 and its glycolyl form Neu5Gc,9Ac. Importantly, the enzyme did not remove acetyl groups positioned at the 4-O position (Neu5,4Ac2). In addition NanS can act upon complex N-glycans released from a glycoprotein [erythropoietin (EPO)], bovine submaxillary mucin and oral epithelial cell-bound glycans. When incubated with its cognate sialidase, NanS increased sialic acid release from mucin and oral epithelial cell surfaces, implying that this esterase improves sialic acid harvesting for this pathogen and potentially other members of the oral microbiome. In summary, we have characterized a novel sialate-O acetylesterase that contributes to the sialobiology of this important human pathogen and has potential applications in the analysis of sialic acid diacetylation of biologics in the pharmaceutical industry. PMID- 26378151 TI - miRNA let-7 expression is regulated by glucose and TNF-alpha by a remote upstream promoter. AB - miRNAs regulate protein abundance and control diverse aspects of cellular processes and biological functions in metabolic diseases, such as obesity and type 2 diabetes (T2D). Let (lethal)-7 miRNAs specifically targets genes associated with T2D and have been implicated in the regulation of peripheral glucose metabolism, yet the direct regulators of let-7 miRNA expression are unknown. In the present study, we report on a putative promoter region for the let-7a-1, let-7f-1 and let-7d gene cluster on chromosome 9 and characterize the promoter activity of this novel area. We show that promoter activity and let-7 miRNA expression is dynamically regulated in response to different factors including serum, glucose, tumour necrosis factor (TNF)-alpha and caffeine. These findings will contribute to understanding the interaction between precise promoter elements to control the transcription and translation of let-7 miRNA genes. PMID- 26378153 TI - Farmworker Housing: A Photo Essay. AB - Migrant and seasonal farmworkers often reside in poor housing conditions which expose them to numerous hazards. These housing conditions are an issue of environmental health and justice. The photographs in this essay illustrate the living conditions confronted by farmworkers, offering a visual context for the reviews published in this issue of New Solutions. Farmworker housing conditions are often shocking to those who have not visited farmworker communities. Continued research is needed to document these conditions, how they affect the health of farmworkers, and provide leverage in the struggle to improve farmworker housing conditions. PMID- 26378152 TI - LKB1 deletion causes early changes in atrial channel expression and electrophysiology prior to atrial fibrillation. AB - AIMS: Liver kinase B1 (LKB1) is a protein kinase that activates the metabolic regulator AMP-activated protein kinase (AMPK) and other related kinases. Deletion of LKB1 in mice leads to cardiomyopathy and atrial fibrillation (AF). However, the specific role of the LKB1 pathway in early atrial biology remains unknown. Thus, we investigated whether LKB1 deletion altered atrial channel expression and electrophysiological function in a cardiomyocyte-specific knockout mouse model. METHODS AND RESULTS: We performed a systematic comparison of alphaMHC-Cre LKB1(fl/fl) and littermate LKB1(fl/fl) male mice. This included analysis of gene expression, histology, and echocardiography, as well as cellular and tissue-level electrophysiology using patch-clamp recordings in vitro, optical mapping ex vivo, and ECG recordings in vivo. At postnatal day 1, atrial depolarization was prolonged, and Nav1.5 and Cx40 expression were markedly down-regulated in MHC-Cre LKB1(fl/fl) mice. Inward sodium current density was significantly decreased in MHC-Cre LKB1(fl/fl) neonatal atrial myocytes. Subsequently, additional alterations in atrial channel expression, atrial fibrosis, and spontaneous onset of AF developed by 2 weeks of age. In adult mice, abnormalities of interatrial conduction and bi-atrial electrical coupling were observed, likely promoting the perpetuation of AF. Mice with AMPK-inactivated hearts demonstrated modest overlap in channel expression with MHC-Cre LKB1(fl/fl) hearts, but retained normal structure, electrophysiological function and contractility. CONCLUSIONS: Deletion of LKB1 causes early defects in atrial channel expression, action potential generation and conduction, which precede widespread atrial remodelling, fibrosis and AF. LKB1 is critical for normal atrial growth and electrophysiological function. PMID- 26378154 TI - Federal Farmworker Housing Standards and Regulations, Their Promise and Limitations, and Implications for Farmworker Health. AB - The housing available to most farmworkers is substandard and unacceptable in 21st century America. The federal government established minimal occupational safety and health standards applicable to migrant farmworker labor camps decades ago, and some states have statutory schemes and regulations that set standards for farm labor camps and employee housing. Many of these federal and state regulations no longer reflect current employment and housing trends, and enforcement success varies greatly. These regulations implicitly recognize the connection between housing conditions and health, but do not effectively address that connection. This review describes the current state of farmworker housing, discusses laws and regulations pertaining to such housing, and highlights the literature on health risks associated with inadequate housing. We propose specific recommendations to strengthen enforcement and reduce the risks of substandard housing for the health of farmworkers and their families. PMID- 26378155 TI - Farmworkers Make Their Voices Heard in the Call for Stronger Protections from Pesticides. AB - Farmworkers are calling for stronger workplace protections to prevent pesticide exposure and reduce health risks for workers and their families. In 1992, the U.S. Environmental Protection Agency (EPA) promulgated the Worker Protection Standard (WPS) as the primary set of regulations protecting the nation's 1-2 million farmworkers from occupational pesticide exposure. After more than 20 years, the EPA proposed revisions to the WPS. The proposed revisions were posted in the Federal Register and made available for public comment on 19 March 2014. In response to these revisions, farmworker organizations conducted outreach in agricultural communities to document and submit farmworkers' first-hand accounts of pesticide exposure as public comments. Through this process, farmworkers--a typically underrepresented, poorly protected, and disenfranchised population- made their voices heard and advocated for changes to improve their health and safety. Their comments in this article articulate the need for stronger workplace protections and enforcement measures to reduce health risks for workers, families, and communities. PMID- 26378156 TI - Farmworker Housing Quality and Health. AB - On 11 November 2014, Farmworker Housing Quality and Health: A Transdisciplinary Conference was convened to draw together experts from the variety of disciplines who contribute to research and practice focused on farmworker housing and health in order to delineate current knowledge and propose next steps. The conference addressed three specific aims: (1) to consolidate current knowledge on characteristics and quality of housing provided for farmworkers; (2) to delineate pertinent directions and areas for farmworker housing health and safety research and policy; and (3) to facilitate the development of working groups to support the implementation of research, education, and engineering projects to improve farmworker housing. This article provides an overview of the conference. PMID- 26378157 TI - Activity of single-agent decitabine in atypical chronic myeloid leukemia. AB - Atypical chronic myeloid leukemia is a rare entity that presents diagnostic and therapeutic challenges. Traditionally utilized therapeutic agents such as hydroxyurea or interferon result in a median survival of approximately two years, thus warranting identification of better options. We report a 49-year-old Caucasian female, who presented with extreme leukocytosis (white blood cells of 148,300/uL) with left shift, severe anemia, and thrombocytopenia. Following a diagnosis of atypical chronic myeloid leukemia, she was started on intravenous decitabine. She subsequently developed paraneoplastic vasculitis of large arteries, which responded to high-dose glucocorticoid. Decitabine therapy resulted in an excellent hematologic response, transfusion independence, and successful transition to an allogeneic peripheral stem cell transplantation. However, the patient subsequently succumbed to the complications of acute graft versus-host-disease. This case illustrates an association between atypical chronic myeloid leukemia and steroid-responsive paraneoplastic vasculitis and highlights the single-agent disease activity of decitabine in atypical chronic myeloid leukemia, which may be utilized as a bridging therapy to allogeneic stem cell transplantation. PMID- 26378158 TI - Comorbidities among patients with cancer who do and do not develop febrile neutropenia during the first chemotherapy cycle. AB - Patients receiving myelosuppressive chemotherapy with certain comorbidities are at increased risk of febrile neutropenia. A comprehensive evaluation of febrile neutropenia-related comorbidities across cancers is needed. This study compared comorbidity prevalence among patients with cancer who did and did not develop febrile neutropenia during the first chemotherapy cycle. This case-control study used administrative claims from adult patients with non-Hodgkin lymphoma or breast, lung, colorectal, ovarian, or gastric cancer who received chemotherapy between 2007 and 2012. Each patient who developed febrile neutropenia (case) was matched with up to four patients without febrile neutropenia (controls) by cancer type, metastasis, chemotherapy regimen, age group, and sex. For each comorbidity (identified in the year before chemotherapy began), the adjusted odds ratio (aOR) for febrile neutropenia by cancer type was evaluated using conditional logistic regression models adjusted for potential confounding factors. Of 31,331 eligible patients, 672 developed febrile neutropenia in the first chemotherapy cycle. A total of 3312 febrile neutropenia cases and matched controls were analyzed. Across tumor types, comorbidity prevalence was higher in patients who developed febrile neutropenia than in those without febrile neutropenia. Among patients with breast cancer, osteoarthritis was more prevalent in patients with febrile neutropenia (aOR, 1.85; 95% CI, 1.07 to 3.18). Among patients with non-Hodgkin lymphoma, renal disease was more prevalent in patients with febrile neutropenia (aOR, 2.25; 95% CI, 1.23 to 4.11). Patients who developed febrile neutropenia in the first chemotherapy cycle presented with comorbidities more often than otherwise similar patients who did not develop febrile neutropenia. These findings warrant further investigation and support the inclusion of comorbidities into febrile neutropenia risk models. PMID- 26378159 TI - Mumps Virus Is Released from the Apical Surface of Polarized Epithelial Cells, and the Release Is Facilitated by a Rab11-Mediated Transport System. AB - Mumps virus (MuV) is an airborne virus that causes a systemic infection in patients. In vivo, the epithelium is a major replication site of MuV, and thus, the mode of MuV infection of epithelial cells is a subject of interest. Our data in the present study showed that MuV entered polarized epithelial cells via both the apical and basolateral surfaces, while progeny viruses were predominantly released from the apical surface. In polarized cells, intracellular transport of viral ribonucleoprotein (vRNP) complexes was dependent on Rab11-positive endosomes, and vRNP complexes were transported to the apical membrane. Expression of a dominant negative form of Rab11 (Rab11S25N) reduced the progeny virus release in polarized cells but not in nonpolarized cells. Although in this way these effects were correlated with cell polarity, Rab11S25N did not modulate the direction of virus release from the apical surface. Therefore, our data suggested that Rab11 is not a regulator of selective apical release of MuV, although it acts as an activator of virus release from polarized epithelial cells. In addition, our data and previous studies on Sendai virus, respiratory syncytial virus, and measles virus suggested that selective apical release from epithelial cells is used by many paramyxoviruses, even though they cause either a systemic infection or a local respiratory infection. IMPORTANCE: Mumps virus (MuV) is the etiological agent of mumps and causes a systemic infection. However, the precise mechanism by which MuV breaks through the epithelial barriers and achieves a systemic infection remains unclear. In the present study, we show that the entry of MuV is bipolar, while the release is predominantly from the apical surface in polarized epithelial cells. In addition, the release of progeny virus was facilitated by a Rab11-positive recycling endosome and microtubule network. Our data provide important insights into the mechanism of transmission and pathogenesis of MuV. PMID- 26378160 TI - RIG-I Signaling Is Essential for Influenza B Virus-Induced Rapid Interferon Gene Expression. AB - Influenza B virus causes annual epidemics and, along with influenza A virus, accounts for substantial disease and economic burden throughout the world. Influenza B virus infects only humans and some marine mammals and is not responsible for pandemics, possibly due to a very low frequency of reassortment and a lower evolutionary rate than that of influenza A virus. Influenza B virus has been less studied than influenza A virus, and thus, a comparison of influenza A and B virus infection mechanisms may provide new insight into virus-host interactions. Here we analyzed the early events in influenza B virus infection and interferon (IFN) gene expression in human monocyte-derived macrophages and dendritic cells. We show that influenza B virus induces IFN regulatory factor 3 (IRF3) activation and IFN-lambda1 gene expression with faster kinetics than does influenza A virus, without a requirement for viral protein synthesis or replication. Influenza B virus-induced activation of IRF3 required the fusion of viral and endosomal membranes, and nuclear accumulation of IRF3 and viral NP occurred concurrently. In comparison, immediate early IRF3 activation was not observed in influenza A virus-infected macrophages. Experiments with RIG-I-, MDA5 , and RIG-I/MDA5-deficient mouse fibroblasts showed that RIG-I is the critical pattern recognition receptor needed for the influenza B virus-induced activation of IRF3. Our results show that innate immune mechanisms are activated immediately after influenza B virus entry through the endocytic pathway, whereas influenza A virus avoids early IRF3 activation and IFN gene induction. IMPORTANCE: Recently, a great deal of interest has been paid to identifying the ligands for RIG-I under conditions of natural infection, as many previous studies have been based on transfection of cells with different types of viral or synthetic RNA structures. We shed light on this question by analyzing the earliest step in innate immune recognition of influenza B virus by human macrophages. We show that influenza B virus induces IRF3 activation, leading to IFN gene expression after viral RNPs (vRNPs) are released into the cytosol and are recognized by RIG-I receptor, meaning that the incoming influenza B virus is already able to activate IFN gene expression. In contrast, influenza A (H3N2) virus failed to activate IRF3 at very early times of infection, suggesting that there are differences in innate immune recognition between influenza A and B viruses. PMID- 26378161 TI - Replication and Transmission of the Novel Bovine Influenza D Virus in a Guinea Pig Model. AB - Influenza D virus (FLUDV) is a novel influenza virus that infects cattle and swine. The goal of this study was to investigate the replication and transmission of bovine FLUDV in guinea pigs. Following direct intranasal inoculation of animals, the virus was detected in nasal washes of infected animals during the first 7 days postinfection. High viral titers were obtained from nasal turbinates and lung tissues of directly inoculated animals. Further, bovine FLUDV was able to transmit from the infected guinea pigs to sentinel animals by means of contact and not by aerosol dissemination under the experimental conditions tested in this study. Despite exhibiting no clinical signs, infected guinea pigs developed seroconversion and the viral antigen was detected in lungs of animals by immunohistochemistry. The observation that bovine FLUDV replicated in the respiratory tract of guinea pigs was similar to observations described previously in studies of gnotobiotic calves and pigs experimentally infected with bovine FLUDV but different from those described previously in experimental infections in ferrets and swine with a swine FLUDV, which supported virus replication only in the upper respiratory tract and not in the lower respiratory tract, including lung. Our study established that guinea pigs could be used as an animal model for studying this newly emerging influenza virus. IMPORTANCE: Influenza D virus (FLUDV) is a novel emerging pathogen with bovine as its primary host. The epidemiology and pathogenicity of the virus are not yet known. FLUDV also spreads to swine, and the presence of FLUDV-specific antibodies in humans could indicate that there is a potential for zoonosis. Our results showed that bovine FLUDV replicated in the nasal turbinate and lungs of guinea pigs at high titers and was also able to transmit from an infected animal to sentinel animals by contact. The fact that bovine FLUDV replicated productively in both the upper and lower respiratory tracts of guinea pigs, similarly to virus infection in its native host, demonstrates that guinea pigs would be a suitable model host to study the replication and transmission potential of bovine FLUDV. PMID- 26378162 TI - Mimivirus Fibrils Are Important for Viral Attachment to the Microbial World by a Diverse Glycoside Interaction Repertoire. AB - Acanthamoeba polyphaga mimivirus (APMV) is a giant virus from the Mimiviridae family. It has many unusual features, such as a pseudoicosahedral capsid that presents a starfish shape in one of its vertices, through which the ~ 1.2-Mb double-stranded DNA is released. It also has a dense glycoprotein fibril layer covering the capsid that has not yet been functionally characterized. Here, we verified that although these structures are not essential for viral replication, they are truly necessary for viral adhesion to amoebae, its natural host. In the absence of fibrils, APMV had a significantly lower level of attachment to the Acanthamoeba castellanii surface. This adhesion is mediated by glycans, specifically, mannose and N-acetylglucosamine (a monomer of chitin and peptidoglycan), both of which are largely distributed in nature as structural components of several organisms. Indeed, APMV was able to attach to different organisms, such as Gram-positive bacteria, fungi, and arthropods, but not to Gram negative bacteria. This prompted us to predict that (i) arthropods, mainly insects, might act as mimivirus dispersers and (ii) by attaching to other microorganisms, APMV could be ingested by amoebae, leading to the successful production of viral progeny. To date, this mechanism has never been described in the virosphere. IMPORTANCE: APMV is a giant virus that is both genetically and structurally complex. Its size is similar to that of small bacteria, and it replicates inside amoebae. The viral capsid is covered by a dense glycoprotein fibril layer, but its function has remained unknown, until now. We found that the fibrils are not essential for mimivirus replication but that they are truly necessary for viral adhesion to the cell surface. This interaction is mediated by glycans, mainly N-acetylglucosamine. We also verified that APMV is able to attach to bacteria, fungi, and arthropods. This indicates that insects might act as mimivirus dispersers and that adhesion to other microorganisms could facilitate viral ingestion by amoebae, a mechanism never before described in the virosphere. PMID- 26378163 TI - Severe Acute Respiratory Syndrome Coronavirus ORF7a Inhibits Bone Marrow Stromal Antigen 2 Virion Tethering through a Novel Mechanism of Glycosylation Interference. AB - Severe acute respiratory syndrome (SARS) emerged in November 2002 as a case of atypical pneumonia in China, and the causative agent of SARS was identified to be a novel coronavirus, severe acute respiratory syndrome coronavirus (SARS-CoV). Bone marrow stromal antigen 2 (BST-2; also known as CD317 or tetherin) was initially identified to be a pre-B-cell growth promoter, but it also inhibits the release of virions of the retrovirus human immunodeficiency virus type 1 (HIV-1) by tethering budding virions to the host cell membrane. Further work has shown that BST-2 restricts the release of many other viruses, including the human coronavirus 229E (hCoV-229E), and the genomes of many of these viruses encode BST 2 antagonists to overcome BST-2 restriction. Given the previous studies on BST-2, we aimed to determine if BST-2 has the ability to restrict SARS-CoV and if the SARS-CoV genome encodes any proteins that modulate BST-2's antiviral function. Through an in vitro screen, we identified four potential BST-2 modulators encoded by the SARS-CoV genome: the papain-like protease (PLPro), nonstructural protein 1 (nsp1), ORF6, and ORF7a. As the function of ORF7a in SARS-CoV replication was previously unknown, we focused our study on ORF7a. We found that BST-2 does restrict SARS-CoV, but the loss of ORF7a leads to a much greater restriction, confirming the role of ORF7a as an inhibitor of BST-2. We further characterized the mechanism of BST-2 inhibition by ORF7a and found that ORF7a localization changes when BST-2 is overexpressed and ORF7a binds directly to BST-2. Finally, we also show that SARS-CoV ORF7a blocks the restriction activity of BST-2 by blocking the glycosylation of BST-2. IMPORTANCE: The severe acute respiratory syndrome coronavirus (SARS-CoV) emerged from zoonotic sources in 2002 and caused over 8,000 infections and 800 deaths in 37 countries around the world. Identifying host factors that regulate SARS-CoV pathogenesis is critical to understanding how this lethal virus causes disease. We have found that BST-2 is capable of restricting SARS-CoV release from cells; however, we also identified a SARS-CoV protein that inhibits BST-2 function. We show that the SARS-CoV protein ORF7a inhibits BST-2 glycosylation, leading to a loss of BST-2's antiviral function. PMID- 26378165 TI - Characterization of a Novel Hepadnavirus in the White Sucker (Catostomus commersonii) from the Great Lakes Region of the United States. AB - The white sucker Catostomus commersonii is a freshwater teleost often utilized as a resident sentinel. Here, we sequenced the full genome of a hepatitis B-like virus that infects white suckers from the Great Lakes Region of the United States. Dideoxy sequencing confirmed that the white sucker hepatitis B virus (WSHBV) has a circular genome (3,542 bp) with the prototypical codon organization of hepadnaviruses. Electron microscopy demonstrated that complete virions of approximately 40 nm were present in the plasma of infected fish. Compared to avi- and orthohepadnaviruses, sequence conservation of the core, polymerase, and surface proteins was low and ranged from 16 to 27% at the amino acid level. An X protein homologue common to the orthohepadnaviruses was not present. The WSHBV genome included an atypical, presumptively noncoding region absent in previously described hepadnaviruses. Phylogenetic analyses confirmed WSHBV as distinct from previously documented hepadnaviruses. The level of divergence in protein sequences between WSHBV and other hepadnaviruses and the identification of an HBV like sequence in an African cichlid provide evidence that a novel genus of the family Hepadnaviridae may need to be established that includes these hepatitis B like viruses in fishes. Viral transcription was observed in 9.5% (16 of 169) of white suckers evaluated. The prevalence of hepatic tumors in these fish was 4.9%, and only 2.4% of fish were positive for both virus and hepatic tumors. These results are not sufficient to draw inferences regarding the association of WSHBV and carcinogenesis in white sucker. IMPORTANCE: We report the first full-length genome of a hepadnavirus from fishes. Phylogenetic analysis of this genome indicates divergence from genomes of previously described hepadnaviruses from mammalian and avian hosts and supports the creation of a novel genus. The discovery of this novel virus may better our understanding of the evolutionary history of hepatitis B-like viruses of other hosts. In fishes, knowledge of this virus may provide insight regarding possible risk factors associated with hepatic neoplasia in the white sucker. This may also offer another model system for mechanistic research. PMID- 26378164 TI - Evidence for an Ancestral Association of Human Coronavirus 229E with Bats. AB - We previously showed that close relatives of human coronavirus 229E (HCoV-229E) exist in African bats. The small sample and limited genomic characterizations have prevented further analyses so far. Here, we tested 2,087 fecal specimens from 11 bat species sampled in Ghana for HCoV-229E-related viruses by reverse transcription-PCR (RT-PCR). Only hipposiderid bats tested positive. To compare the genetic diversity of bat viruses and HCoV-229E, we tested historical isolates and diagnostic specimens sampled globally over 10 years. Bat viruses were 5- and 6-fold more diversified than HCoV-229E in the RNA-dependent RNA polymerase (RdRp) and spike genes. In phylogenetic analyses, HCoV-229E strains were monophyletic and not intermixed with animal viruses. Bat viruses formed three large clades in close and more distant sister relationships. A recently described 229E-related alpaca virus occupied an intermediate phylogenetic position between bat and human viruses. According to taxonomic criteria, human, alpaca, and bat viruses form a single CoV species showing evidence for multiple recombination events. HCoV-229E and the alpaca virus showed a major deletion in the spike S1 region compared to all bat viruses. Analyses of four full genomes from 229E-related bat CoVs revealed an eighth open reading frame (ORF8) located at the genomic 3' end. ORF8 also existed in the 229E-related alpaca virus. Reanalysis of HCoV-229E sequences showed a conserved transcription regulatory sequence preceding remnants of this ORF, suggesting its loss after acquisition of a 229E-related CoV by humans. These data suggested an evolutionary origin of 229E-related CoVs in hipposiderid bats, hypothetically with camelids as intermediate hosts preceding the establishment of HCoV-229E. IMPORTANCE: The ancestral origins of major human coronaviruses (HCoVs) likely involve bat hosts. Here, we provide conclusive genetic evidence for an evolutionary origin of the common cold virus HCoV-229E in hipposiderid bats by analyzing a large sample of African bats and characterizing several bat viruses on a full-genome level. Our evolutionary analyses show that animal and human viruses are genetically closely related, can exchange genetic material, and form a single viral species. We show that the putative host switches leading to the formation of HCoV-229E were accompanied by major genomic changes, including deletions in the viral spike glycoprotein gene and loss of an open reading frame. We reanalyze a previously described genetically related alpaca virus and discuss the role of camelids as potential intermediate hosts between bat and human viruses. The evolutionary history of HCoV-229E likely shares important characteristics with that of the recently emerged highly pathogenic Middle East respiratory syndrome (MERS) coronavirus. PMID- 26378166 TI - CD8low CD100- T Cells Identify a Novel CD8 T Cell Subset Associated with Viral Control during Human Hantaan Virus Infection. AB - Hantaan virus (HTNV) infection can cause a severe lethal hemorrhagic fever with renal syndrome (HFRS) in humans. CD8(+) T cells play a critical role in combating HTNV infections. However, the contributions of different CD8(+) T cell subsets to the immune response against viral infection are poorly understood. Here, we identified a novel subset of CD8(+) T cells characterized by the CD8(low) CD100( ) phenotype in HFRS patients. The CD8(low) CD100(-) subset accounted for a median of 14.3% of the total CD8(+) T cells in early phase of HFRS, and this percentage subsequently declined in the late phase of infection, whereas this subset was absent in healthy controls. Furthermore, the CD8(low) CD100(-) cells were associated with high activation and expressed high levels of cytolytic effector molecules and exhibited a distinct expression profile of effector CD8(+) T cells (CCR7(+/-) CD45RA(-) CD127(high) CD27(int) CD28(low) CD62L(-)). When stimulated with specific HTNV nucleocapsid protein-derived peptide pools, most responding CD8(+) cells (gamma interferon [IFN-gamma] positive and/or tumor necrosis factor alpha [TNF-alpha] positive) were CD8(low) CD100(-) cells. The frequency of CD8(low) CD100(-) cells among HTNV-specific CD8(+) T cells was higher in milder cases than in more severe cases. Importantly, the proportion of the CD8(low) CD100(-) subset among CD8(+) T cells in early phase of HFRS was negatively correlated with the HTNV viral load, suggesting that CD8(low) CD100(-) cells may be associated with viral clearance. The contraction of the CD8(low) CD100(-) subset in late phase of infection may be related to the consistently high expression levels of PD-1. These results may provide new insights into our understanding of CD8(+) T cell-mediated protective immunity as well as immune homeostasis after HTNV infection in humans. IMPORTANCE: CD8(+) T cells play important roles in the antiviral immune response. We found that the proportion of CD8(low) CD100(-) cells among CD8(+) T cells from HFRS patients was negatively correlated with the HTNV viral load, and the frequency of CD8(low) CD100(-) cells among virus-specific CD8(+) T cells was higher in milder HFRS cases than in more severe cases. These results imply a beneficial role for the CD8(low) CD100(-) cell subset in viral control during human HTNV infection. PMID- 26378167 TI - Regulation of Viral RNA Synthesis by the V Protein of Parainfluenza Virus 5. AB - Paramyxoviruses include many important animal and human pathogens. The genome of parainfluenza virus 5 (PIV5), a prototypical paramyxovirus, encodes a V protein that inhibits viral RNA synthesis. In this work, the mechanism of inhibition was investigated. Using mutational analysis and a minigenome system, we identified regions in the N and C termini of the V protein that inhibit viral RNA synthesis: one at the very N terminus of V and the second at the C terminus of V. Furthermore, we determined that residues L16 and I17 are critical for the inhibitory function of the N-terminal region of the V protein. Both regions interact with the nucleocapsid protein (NP), an essential component of the viral RNA genome complex (RNP). Mutations at L16 and I17 abolished the interaction between NP and the N-terminal domain of V. This suggests that the interaction between NP and the N-terminal domain plays a critical role in V inhibition of viral RNA synthesis by the N-terminal domain. Both the N- and C-terminal regions inhibited viral RNA replication. The C terminus inhibited viral RNA transcription, while the N-terminal domain enhanced viral RNA transcription, suggesting that the two domains affect viral RNA through different mechanisms. Interestingly, V also inhibited the synthesis of the RNA of other paramyxoviruses, such as Nipah virus (NiV), human parainfluenza virus 3 (HPIV3), measles virus (MeV), mumps virus (MuV), and respiratory syncytial virus (RSV). This suggests that a common host factor may be involved in the replication of these paramyxoviruses. IMPORTANCE: We identified two regions of the V protein that interact with NP and determined that one of these regions enhances viral RNA transcription via its interaction with NP. Our data suggest that a common host factor may be involved in the regulation of paramyxovirus replication and could be a target for broad antiviral drug development. Understanding the regulation of paramyxovirus replication will enable the rational design of vaccines and potential antiviral drugs. PMID- 26378168 TI - A Novel Tricyclic Polyketide, Vanitaracin A, Specifically Inhibits the Entry of Hepatitis B and D Viruses by Targeting Sodium Taurocholate Cotransporting Polypeptide. AB - Anti-hepatitis B virus (HBV) drugs are currently limited to nucleos(t)ide analogs (NAs) and interferons. A challenge of drug development is the identification of small molecules that suppress HBV infection from new chemical sources. Here, from a fungus-derived secondary metabolite library, we identify a structurally novel tricyclic polyketide, named vanitaracin A, which specifically inhibits HBV infection. Vanitaracin A inhibited the viral entry process with a submicromolar 50% inhibitory concentration (IC50) (IC50 = 0.61 +/- 0.23 MUM), without evident cytotoxicity (50% cytotoxic concentration of >256 MUM; selectivity index value of >419) in primary human hepatocytes. Vanitaracin A did not affect the HBV replication process. This compound was found to directly interact with the HBV entry receptor sodium taurocholate cotransporting polypeptide (NTCP) and impaired its bile acid transport activity. Consistent with this NTCP targeting, antiviral activity of vanitaracin A was observed with hepatitis D virus (HDV) but not hepatitis C virus. Importantly, vanitaracin A inhibited infection by all HBV genotypes tested (genotypes A to D) and clinically relevant NA-resistant HBV isolate. Thus, we identified a fungal metabolite, vanitaracin A, which was a potent, well-tolerated, and broadly active inhibitor of HBV and HDV entry. This compound, or its related analogs, could be part of an antiviral strategy for preventing reinfection with HBV, including clinically relevant nucleos(t)ide analog-resistant virus. IMPORTANCE: For achieving better treatment and prevention of hepatitis B virus (HBV) infection, anti-HBV agents targeting a new molecule are in great demand. Although sodium taurocholate cotransporting polypeptide (NTCP) has recently been reported to be an essential host factor for HBV entry, there is a limited number of reports that identify new compounds targeting NTCP and inhibiting HBV entry. Here, from an uncharacterized chemical library, we isolated a structurally new compound, named vanitaracin A, which inhibited the process of entry of HBV and hepatitis D virus (HDV). This compound was suggested to directly interact with NTCP and inhibit its transporter activity. Importantly, vanitaracin A inhibited the entry of all HBV genotypes examined and of a clinically relevant nucleos(t)ide analog-resistant HBV isolate. PMID- 26378169 TI - Structural and Thermodynamic Basis of Epitope Binding by Neutralizing and Nonneutralizing Forms of the Anti-HIV-1 Antibody 4E10. AB - The 4E10 antibody recognizes the membrane-proximal external region (MPER) of the HIV-1 Env glycoprotein gp41 transmembrane subunit, exhibiting one of the broadest neutralizing activities known to date. The neutralizing activity of 4E10 requires solvent-exposed hydrophobic residues at the apex of the complementarity determining region (CDR) H3 loop, but the molecular basis for this requirement has not been clarified. Here, we report the cocrystal structures and the energetic parameters of binding of a peptide bearing the 4E10-epitope sequence (4E10ep) to nonneutralizing versions of the 4E10 Fab. Nonneutralizing Fabs were obtained by shortening and decreasing the hydrophobicity of the CDR-H3 loop (termed DeltaLoop) or by substituting the two tryptophan residues of the CDR-H3 apex with Asp residues (termed WDWD), which also decreases hydrophobicity but preserves the length of the loop. The analysis was complemented by the first crystal structure of the 4E10 Fab in its ligand-free state. Collectively, the data ruled out major conformational changes of CDR-H3 at any stage during the binding process (equilibrium or transition state). Although these mutations did not impact the affinity of wild-type Fab for the 4E10ep in solution, the two nonneutralizing versions of 4E10 were deficient in binding to MPER inserted in the plasma membrane (mimicking the environment faced by the antibody in vivo). The conclusions of our structure-function analysis strengthen the idea that to exert effective neutralization, the hydrophobic apex of the solvent-exposed CDR H3 loop must recognize an antigenic structure more complex than just the linear alpha-helical epitope and likely constrained by the viral membrane lipids. IMPORTANCE: The broadly neutralizing anti-HIV-1 4E10 antibody blocks infection caused by nearly all viral strains and isolates examined thus far. However, 4E10 (or 4E10-like) antibodies are rarely found in HIV-1-infected individuals or elicited through vaccination. Impediments to the design of successful 4E10 immunogens are partly attributed to an incomplete understanding of the structural and binding characteristics of this class of antibodies. Since the broadly neutralizing activity of 4E10 is abrogated by mutations of the tip of the CDR-H3, we investigated their impact on binding of the MPER-epitope at the atomic and energetic levels. We conclude that the difference between neutralizing and nonneutralizing antibodies of 4E10 is neither structural nor energetic but is related to the capacity to recognize the HIV-1 gp41 epitope inserted in biological membranes. Our findings strengthen the idea that to elicit similar neutralizing antibodies, the suitable MPER vaccine must be "delivered" in a membrane environment. PMID- 26378170 TI - Role of Substitutions in the Hemagglutinin in the Emergence of the 1968 Pandemic Influenza Virus. AB - Hemagglutinin (HA) of H3N2/1968 pandemic influenza viruses differs from the putative avian precursor by seven amino acid substitutions. Substitutions Q226L and G228S are known to be essential for adaptation of avian HA to mammals. We found that introduction of avian-virus-like amino acids at five other HA positions (positions 62, 81, 92, 144, and 193) of A/Hong Kong/1/1968 virus decreased viral replication in human cells and transmission in pigs. Thus, substitutions at some of these positions facilitated emergence of the pandemic virus. PMID- 26378171 TI - Vaccine-Derived Neutralizing Antibodies to the Human Cytomegalovirus gH/gL Pentamer Potently Block Primary Cytotrophoblast Infection. AB - Human cytomegalovirus (HCMV) elicits neutralizing antibodies (NAb) of various potencies and cell type specificities to prevent HCMV entry into fibroblasts (FB) and epithelial/endothelial cells (EpC/EnC). NAb targeting the major essential envelope glycoprotein complexes gB and gH/gL inhibit both FB and EpC/EnC entry. In contrast to FB infection, HCMV entry into EpC/EnC is additionally blocked by extremely potent NAb to conformational epitopes of the gH/gL/UL128/130/131A pentamer complex (PC). We recently developed a vaccine concept based on coexpression of all five PC subunits by a single modified vaccinia virus Ankara (MVA) vector, termed MVA-PC. Vaccination of mice and rhesus macaques with MVA-PC resulted in a high titer and sustained NAb that blocked EpC/EnC infection and lower-titer NAb that inhibited FB entry. However, antibody function responsible for the neutralizing activity induced by the MVA-PC vaccine is uncharacterized. Here, we demonstrate that MVA-PC elicits NAb with cell type-specific neutralization potency and antigen recognition pattern similar to human NAb targeting conformational and linear epitopes of the UL128/130/131A subunits or gH. In addition, we show that the vaccine-derived PC-specific NAb are significantly more potent than the anti-gH NAb to prevent HCMV spread in EpC and infection of human placental cytotrophoblasts, cell types thought to be of critical importance for HCMV transmission to the fetus. These findings further validate MVA-PC as a clinical vaccine candidate to elicit NAb that resembles those induced during HCMV infection and provide valuable insights into the potency of PC-specific NAb to interfere with HCMV cell-associated spread and infection of key placental cells. IMPORTANCE: As a consequence of the leading role of human cytomegalovirus (HCMV) in causing permanent birth defects, developing a vaccine against HCMV has been assigned a major public health priority. We have recently introduced a vaccine strategy based on a widely used, safe, and well-characterized poxvirus vector platform to elicit potent and durable neutralizing antibody (NAb) responses targeting the HCMV envelope pentamer complex (PC), which has been suggested as a critical component for a vaccine to prevent congenital HCMV infection. With this work, we confirm that the NAb elicited by the vaccine vector have properties that are similar to those of human NAb isolated from individuals chronically infected with HCMV. In addition, we show that PC-specific NAb have potent ability to prevent infection of key placental cells that HCMV utilizes to cross the fetal-maternal interface, suggesting that NAb targeting the PC may be essential to prevent HCMV vertical transmission. PMID- 26378173 TI - A Population Genetics Perspective on Geminivirus Infection. AB - The selective accumulation of both DNA components of a bipartite geminivirus, Abutilon mosaic virus, was recorded during early systemic infection of Nicotiana benthamiana plants. Purified nuclei were diagnosed for viral DNA using hybridization specific for DNA A or DNA B to detect these individual genome components either alone or both simultaneously by dual-color staining. Although this virus needs both components for symptomatic infection, DNA A alone was transported to upper leaves, where it was imported into phloem nuclei and replicated autonomously. The coinfection with DNA A and DNA B revealed an independent spread of both molecules, which resulted in a stochastic distribution of DNA A- and DNA A/B-infected nuclei. A population genetics evaluation of the respective frequencies was compared to a model computation. This elucidated a surprisingly simple relationship between the initial frequencies of the viral DNA components and the number of susceptible cells during the course of early systemic infection. IMPORTANCE: For bipartite begomoviruses, DNA B-independent long-distance spread of DNA A has been described before, but it has never been shown whether viral DNA A alone invades nuclei of systemic tissues and replicates therein. This is demonstrated now for the first time. During infection with DNA A and DNA B, a similar solitary spread of DNA A can be recognized at early stages. We describe a population genetics model of how the hit probabilities of DNA A and DNA B for susceptible cells determine the relative frequencies of either genome component during the course of infection. PMID- 26378172 TI - Differential Susceptibilities of Human Lung Primary Cells to H1N1 Influenza Viruses. AB - Human alveolar epithelial cells (AECs) and alveolar macrophages (AMs) are the first lines of lung defense. Here, we report that AECs are the direct targets for H1N1 viruses that have circulated since the 2009 pandemic (H1N1pdm09). AMs are less susceptible to H1N1pdm09 virus, but they produce significantly more inflammatory cytokines than AECs from the same donor. AECs form an intact epithelial barrier that is destroyed by H1N1pdm09 infection. However, there is significant variation in the cellular permissiveness to H1N1pdm09 infection among different donors. AECs from obese donors appear to be more susceptible to H1N1pdm09 infection, whereas gender, smoking history, and age do not appear to affect AEC susceptibility. There is also a difference in response to different strains of H1N1pdm09 viruses. Compared to A/California04/09 (CA04), A/New York/1682/09 (NY1682) is more infectious and causes more epithelial barrier injury, although it stimulates less cytokine production. We further determined that a single amino acid residue substitution in NY1682 hemagglutinin is responsible for the difference in infectivity. In conclusion, this is the first study of host susceptibility of human lung primary cells and the integrity of the alveolar epithelial barrier to influenza. Further elucidation of the mechanism of increased susceptibility of AECs from obese subjects may facilitate the development of novel protection strategies against influenza virus infection. IMPORTANCE: Disease susceptibility of influenza is determined by host and viral factors. Human alveolar epithelial cells (AECs) form the key line of lung defenses against pathogens. Using primary AECs from different donors, we provided cellular level evidence that obesity might be a risk factor for increased susceptibility to influenza. We also compared the infections of two closely related 2009 pandemic H1N1 strains in AECs from the same donor and identified a key viral factor that affected host susceptibility, the dominance of which may be correlated with disease epidemiology. In addition, primary human AECs can serve as a convenient and powerful model to investigate the mechanism of influenza induced lung injury and determine the effect of genetic and epigenetic factors on host susceptibility to pandemic influenza virus infection. PMID- 26378174 TI - Genomic Analysis, Phenotype, and Virulence of the Historical Brazilian Smallpox Vaccine Strain IOC: Implications for the Origins and Evolutionary Relationships of Vaccinia Virus. AB - Smallpox was declared eradicated in 1980 after an intensive vaccination program using different strains of vaccinia virus (VACV; Poxviridae). VACV strain IOC (VACV-IOC) was the seed strain of the smallpox vaccine manufactured by the major vaccine producer in Brazil during the smallpox eradication program. However, little is known about the biological and immunological features as well as the phylogenetic relationships of this first-generation vaccine. In this work, we present a comprehensive characterization of two clones of VACV-IOC. Both clones had low virulence in infected mice and induced a protective immune response against a lethal infection comparable to the response of the licensed vaccine ACAM2000 and the parental strain VACV-IOC. Full-genome sequencing revealed the presence of several fragmented virulence genes that probably are nonfunctional, e.g., F1L, B13R, C10L, K3L, and C3L. Most notably, phylogenetic inference supported by the structural analysis of the genome ends provides evidence of a novel, independent cluster in VACV phylogeny formed by VACV-IOC, the Brazilian field strains Cantagalo (CTGV) and Serro 2 viruses, and horsepox virus, a VACV like virus supposedly related to an ancestor of the VACV lineage. Our data strongly support the hypothesis that CTGV-like viruses represent feral VACV that evolved in parallel with VACV-IOC after splitting from a most recent common ancestor, probably an ancient smallpox vaccine strain related to horsepox virus. Our data, together with an interesting historical investigation, revisit the origins of VACV and propose new evolutionary relationships between ancient and extant VACV strains, mainly horsepox virus, VACV-IOC/CTGV-like viruses, and Dryvax strain. IMPORTANCE: First-generation vaccines used to eradicate smallpox had rates of adverse effects that are not acceptable by current health care standards. Moreover, these vaccines are genetically heterogeneous and consist of a pool of quasispecies of VACV. Therefore, the search for new-generation smallpox vaccines that combine low pathogenicity, immune protection, and genetic homogeneity is extremely important. In addition, the phylogenetic relationships and origins of VACV strains are quite nebulous. We show the characterization of two clones of VACV-IOC, a unique smallpox vaccine strain that contributed to smallpox eradication in Brazil. The immunogenicity and reduced virulence make the IOC clones good options for alternative second-generation smallpox vaccines. More importantly, this study reveals the phylogenetic relationship between VACV-IOC, feral VACV established in nature, and the ancestor-like horsepox virus. Our data expand the discussion on the origins and evolutionary connections of VACV lineages. PMID- 26378175 TI - Dengue Virus NS1 Protein Modulates Cellular Energy Metabolism by Increasing Glyceraldehyde-3-Phosphate Dehydrogenase Activity. AB - Dengue is one of the main public health concerns worldwide. Recent estimates indicate that over 390 million people are infected annually with the dengue virus (DENV), resulting in thousands of deaths. Among the DENV nonstructural proteins, the NS1 protein is the only one whose function during replication is still unknown. NS1 is a 46- to 55-kDa glycoprotein commonly found as both a membrane associated homodimer and a soluble hexameric barrel-shaped lipoprotein. Despite its role in the pathogenic process, NS1 is essential for proper RNA accumulation and virus production. In the present study, we identified that glyceraldehyde-3 phosphate dehydrogenase (GAPDH) interacts with intracellular NS1. Molecular docking revealed that this interaction occurs through the hydrophobic protrusion of NS1 and the hydrophobic residues located at the opposite side of the catalytic site. Moreover, addition of purified recombinant NS1 enhanced the glycolytic activity of GAPDH in vitro. Interestingly, we observed that DENV infection promoted the relocalization of GAPDH to the perinuclear region, where NS1 is commonly found. Both DENV infection and expression of NS1 itself resulted in increased GAPDH activity. Our findings indicate that the NS1 protein acts to increase glycolytic flux and, consequently, energy production, which is consistent with the recent finding that DENV induces and requires glycolysis for proper replication. This is the first report to propose that NS1 is an important modulator of cellular energy metabolism. The data presented here provide new insights that may be useful for further drug design and the development of alternative antiviral therapies against DENV. IMPORTANCE: Dengue represents a serious public health problem worldwide and is caused by infection with dengue virus (DENV). Estimates indicate that half of the global population is at risk of infection, with almost 400 million cases occurring per year. The NS1 glycoprotein is found in both the intracellular and the extracellular milieus. Despite the fact that NS1 has been commonly associated with DENV pathogenesis, it plays a pivotal but unknown role in the replication process. In an effort to understand the role of intracellular NS1, we demonstrate that glyceraldehyde-3-phosphate dehydrogenase (GAPDH) interacts with NS1. Our results indicate that NS1 increases the glycolytic activity of GAPDH in vitro. Interestingly, the GAPDH activity was increased during DENV infection, and NS1 expression alone was sufficient to enhance intracellular GAPDH activity in BHK-21 cells. Overall, our findings suggest that NS1 is an important modulator of cellular energy metabolism by increasing glycolytic flux. PMID- 26378176 TI - Role of gB and pUS3 in Equine Herpesvirus 1 Transfer between Peripheral Blood Mononuclear Cells and Endothelial Cells: a Dynamic In Vitro Model. AB - Infected peripheral blood mononuclear cells (PBMC) effectively transport equine herpesvirus type 1 (EHV-1), but not EHV-4, to endothelial cells (EC) lining the blood vessels of the pregnant uterus or central nervous system, a process that can result in abortion or myeloencephalopathy. We examined, using a dynamic in vitro model, the differences between EHV-1 and EHV-4 infection of PBMC and PBMC EC interactions. In order to evaluate viral transfer between infected PBMC and EC, cocultivation assays were performed. Only EHV-1 was transferred from PBMC to EC, and viral glycoprotein B (gB) was shown to be mainly responsible for this form of cell-to-cell transfer. For addressing the more dynamic aspects of PBMC-EC interaction, infected PBMC were perfused through a flow channel containing EC in the presence of neutralizing antibodies. By simulating capillary blood flow and analyzing the behavior of infected PBMC through live fluorescence imaging and automated cell tracking, we observed that EHV-1 was able to maintain tethering and rolling of infected PBMC on EC more effectively than EHV-4. Deletion of US3 reduced the ability of infected PBMC to tether and roll compared to that of cells infected with parental virus, which resulted in a significant reduction in virus transfer from PBMC to EC. Taking the results together, we conclude that systemic spread and EC infection by EHV-1, but not EHV-4, is caused by its ability to infect and/or reprogram mononuclear cells with respect to their tethering and rolling behavior on EC and consequent virus transfer. IMPORTANCE: EHV-1 is widespread throughout the world and causes substantial economic losses through outbreaks of respiratory disease, abortion, and myeloencephalopathy. Despite many years of research, no fully protective vaccines have been developed, and several aspects of viral pathogenesis still need to be uncovered. In the current study, we investigated the molecular mechanisms that facilitate the cell-associated viremia, which is arguably the most important aspect of EHV-1 pathogenesis. The newly discovered functions of gB and pUS3 add new facets to their previously reported roles. Due to the conserved nature of cell-associated viremia among numerous herpesviruses, these results are also very relevant for viruses such as varicella-zoster virus, pseudorabies virus, human cytomegalovirus, and others. In addition, the constructed mutant and recombinant viruses exhibit potent in vitro replication but have significant defects in certain stages of the disease course. These viruses therefore show much promise as candidates for future live vaccines. PMID- 26378178 TI - Resolving the Origin of Rabbit Hemorrhagic Disease Virus: Insights from an Investigation of the Viral Stocks Released in Australia. AB - To resolve the evolutionary history of rabbit hemorrhagic disease virus (RHDV), we performed a genomic analysis of the viral stocks imported and released as a biocontrol measure in Australia, as well as a global phylogenetic analysis. Importantly, conflicts were identified between the sequences determined here and those previously published that may have affected evolutionary rate estimates. By removing likely erroneous sequences, we show that RHDV emerged only shortly before its initial description in China. PMID- 26378177 TI - Retargeting Oncolytic Vesicular Stomatitis Virus to Human T-Cell Lymphotropic Virus Type 1-Associated Adult T-Cell Leukemia. AB - Adult T cell leukemia/lymphoma (ATL) is an aggressive cancer of CD4/CD25(+) T lymphocytes, the etiological agent of which is human T-cell lymphotropic virus type 1 (HTLV-1). ATL is highly refractory to current therapies, making the development of new treatments a high priority. Oncolytic viruses such as vesicular stomatitis virus (VSV) are being considered as anticancer agents since they readily infect transformed cells compared to normal cells, the former appearing to exhibit defective innate immune responses. Here, we have evaluated the efficacy and safety of a recombinant VSV that has been retargeted to specifically infect and replicate in transformed CD4(+) cells. This was achieved by replacing the single VSV glycoprotein (G) with human immunodeficiency virus type 1 (HIV-1) gp160 to create a hybrid fusion protein, gp160G. The resultant virus, VSV-gp160G, was found to only target cells expressing CD4 and retained robust oncolytic activity against HTLV-1 actuated ATL cells. VSV-gp160G was further noted to be highly attenuated and did not replicate efficiently in or induce significant cell death of primary CD4(+) T cells. Accordingly, VSV-gp160G did not elicit any evidence of neurotoxicity even in severely immunocompromised animals such as NOD/Shi-scid, IL-2Rgamma-c-null (NSG) mice. Importantly, VSV gp160G effectively exerted potent oncolytic activity in patient-derived ATL transplanted into NSG mice and facilitated a significant survival benefit. Our data indicate that VSV-gp160G exerts potent oncolytic efficacy against CD4(+) malignant cells and either alone or in conjunction with established therapies may provide an effective treatment in patients displaying ATL. IMPORTANCE: Adult T cell leukemia (ATL) is a serious form of cancer with a high mortality rate. HTLV 1 infection is the etiological agent of ATL and, unfortunately, most patients succumb to the disease within a few years. Current treatment options have failed to significantly improve survival rate. In this study, we developed a recombinant strain of vesicular stomatitis virus (VSV) that specifically targets transformed CD4(+) T cells through replacement of the G protein of VSV with a hybrid fusion protein, combining domains from gp160 of HIV-1 and VSV-G. This modification eliminated the normally broad tropism of VSV and restricted infection to primarily the transformed CD4(+) cell population. This effect greatly reduced neurotoxic risk associated with VSV infection while still allowing VSV to effectively target ATL cells. PMID- 26378179 TI - Characterization of the Drug Resistance Profiles of Integrase Strand Transfer Inhibitors in Simian Immunodeficiency Virus SIVmac239. AB - We previously showed that the simian immunodeficiency virus SIVmac239 is susceptible to human immunodeficiency virus (HIV) integrase (IN) strand transfer inhibitors (INSTIs) and that the same IN drug resistance mutations result in similar phenotypes in both viruses. Now we wished to determine whether tissue culture drug selection studies with SIV would yield the same resistance mutations as in HIV. Tissue culture selection experiments were performed using rhesus macaque peripheral blood mononuclear cells (PBMCs) infected with SIVmac239 viruses in the presence of increasing concentrations of dolutegravir (DTG), elvitegravir (EVG), and raltegravir (RAL). We now show that 22 weeks of selection pressure with DTG yielded a mutation at position R263K in SIV, similar to what has been observed in HIV, and that selections with EVG led to emergence of the E92Q substitution, which is a primary INSTI resistance mutation in HIV associated with EVG treatment failure. To study this at a biochemical level, purified recombinant SIVmac239 wild-type (WT) and E92Q, T97A, G118R, Y143R, Q148R, N155H, R263K, E92Q T97A, E92Q Y143R, R263K H51Y, and G140S Q148R recombinant substitution-containing IN enzymes were produced, and each of the characteristics strand transfer, 3'-processing activity, and INSTI inhibitory constants was assessed in cell-free assays. The results show that the G118R and G140S Q148R substitutions decreased Km' and Vmax'/Km' for strand transfer compared to those of the WT. RAL and EVG showed reduced activity against both viruses and against enzymes containing Q148R, E92Q Y143R, and G140S Q148R. Both viruses and enzymes containing Q148R and G140S Q148R showed moderate levels of resistance against DTG. This study further confirms that the same mutations associated with drug resistance in HIV display similar profiles in SIV. IMPORTANCE: Our goal was to definitively establish whether HIV and simian immunodeficiency virus (SIV) share similar resistance pathways under tissue culture drug selection pressure with integrase strand transfer inhibitors and to test the effect of HIV-1 integrase resistance-associated mutations on SIV integrase catalytic activity and resistance to integrase strand transfer inhibitors. Clinically relevant HIV integrase resistance-associated mutations were selected in SIV in our tissue culture experiments. Not only do we report on the characterization of SIV recombinant integrase enzyme catalytic activities, we also provide the first research anywhere on the effect of mutations within recombinant integrase SIV enzymes on drug resistance. PMID- 26378180 TI - Deficiencies in Cellular Processes Modulated by the Retinoblastoma Protein Do Not Account for Reduced Human Cytomegalovirus Replication in Its Absence. AB - Despite encoding multiple viral proteins that modulate the retinoblastoma (Rb) protein in a manner classically defined as inactivation, human cytomegalovirus (HCMV) requires the presence of the Rb protein to replicate efficiently. In uninfected cells, Rb controls numerous pathways that the virus also commandeers during infection. These include cell cycle progression, senescence, mitochondrial biogenesis, apoptosis, and glutaminolysis. We investigated whether a potential inability of HCMV to regulate these Rb-controlled pathways in the absence of the Rb protein was the reason for reduced viral productive replication in Rb knockdown cells. We found that HCMV was equally able to modulate these pathways in the parental Rb-expressing and Rb-depleted cells. Our results suggest that Rb may be required to enhance a specific viral process during HCMV productive replication. IMPORTANCE: The retinoblastoma (Rb) tumor suppressor is well established as a repressor of E2F-dependent transcription. Rb hyperphosphorylation, degradation, and binding by viral oncoproteins are also codified. Recent reports indicate Rb can be monophosphorylated, repress the transcription of antiviral genes in association with adenovirus E1A, modulate cellular responses to polycomb-mediated epigenetic methylations in human papillomavirus type 16 E7 expressing cells, and increase the efficiency of human cytomegalovirus (HCMV) productive replication. Since Rb function also now extends to regulation of mitochondrial function (apoptosis, metabolism), it is clear that our current understanding of this protein is insufficient to explain its roles in virus-infected cells and tumors. Work here reinforces this concept, showing the known roles of Rb are insufficient to explain its positive impact on HCMV replication. Therefore, HCMV, along with other viral systems, provide valuable tools to probe functions of Rb that might be modulated with therapeutics for cancers with viral or nonviral etiologies. PMID- 26378181 TI - Differential Reovirus-Specific and Herpesvirus-Specific Activator Protein 1 Activation of Secretogranin II Leads to Altered Virus Secretion. AB - Viruses utilize host cell machinery for propagation and manage to evade cellular host defense mechanisms in the process. Much remains unknown regarding how the host responds to viral infection. We recently performed global proteomic screens of mammalian reovirus TIL- and T3D-infected and herpesvirus (herpes simplex virus 1 [HSV-1])-infected HEK293 cells. The nonenveloped RNA reoviruses caused an upregulation, whereas the enveloped DNA HSV-1 caused a downregulation, of cellular secretogranin II (SCG2). SCG2, a member of the granin family that functions in hormonal peptide sorting into secretory vesicles, has not been linked to virus infections previously. We confirmed SCG2 upregulation and found SCG2 phosphorylation by 18 h postinfection (hpi) in reovirus-infected cells. We also found a decrease in the amount of reovirus secretion from SCG2 knockdown cells. Similar analyses of cells infected with HSV-1 showed an increase in the amount of secreted virus. Analysis of the stress-activated protein kinase (SAPK)/Jun N-terminal protein kinase (JNK) pathway indicated that each virus activates different pathways leading to activator protein 1 (AP-1) activation, which is the known SCG2 transcription activator. We conclude from these experiments that the negative correlation between SCG2 quantity and virus secretion for both viruses indicates a virus-specific role for SCG2 during infection. IMPORTANCE: Mammalian reoviruses affect the gastrointestinal system or cause respiratory infections in humans. Recent work has shown that all mammalian reovirus strains (most specifically T3D) may be useful oncolytic agents. The ubiquitous herpes simplex viruses cause common sores in mucosal areas of their host and have coevolved with hosts over many years. Both of these virus species are prototypical representatives of their viral families, and investigation of these viruses can lead to further knowledge of how they and the other more pathogenic members of their respective families interact with the host. Here we show that secretogranin II (SCG2), a protein not previously studied in the context of virus infections, alters virus output in a virus-specific manner and that the quantity of SCG2 is inversely related to amounts of infectious-virus secretion. Herpesviruses may target this protein to facilitate enhanced virus release from the host. PMID- 26378182 TI - Monoclonal Antibodies Directed toward the Hepatitis C Virus Glycoprotein E2 Detect Antigenic Differences Modulated by the N-Terminal Hypervariable Region 1 (HVR1), HVR2, and Intergenotypic Variable Region. AB - Hepatitis C virus (HCV) envelope glycoproteins E1 and E2 form a heterodimer and mediate receptor interactions and viral fusion. Both E1 and E2 are targets of the neutralizing antibody (NAb) response and are candidates for the production of vaccines that generate humoral immunity. Previous studies demonstrated that N terminal hypervariable region 1 (HVR1) can modulate the neutralization potential of monoclonal antibodies (MAbs), but no information is available on the influence of HVR2 or the intergenotypic variable region (igVR) on antigenicity. In this study, we examined how the variable regions influence the antigenicity of the receptor binding domain of E2 spanning HCV polyprotein residues 384 to 661 (E2661) using a panel of MAbs raised against E2661 and E2661 lacking HVR1, HVR2, and the igVR (Delta123) and well-characterized MAbs isolated from infected humans. We show for a subset of both neutralizing and nonneutralizing MAbs that all three variable regions decrease the ability of MAbs to bind E2661 and reduce the ability of MAbs to inhibit E2-CD81 interactions. In addition, we describe a new MAb directed toward the region spanning residues 411 to 428 of E2 (MAb24) that demonstrates broad neutralization against all 7 genotypes of HCV. The ability of MAb24 to inhibit E2-CD81 interactions is strongly influenced by the three variable regions. Our data suggest that HVR1, HVR2, and the igVR modulate exposure of epitopes on the core domain of E2 and their ability to prevent E2 CD81 interactions. These studies suggest that the function of HVR2 and the igVR is to modulate antibody recognition of glycoprotein E2 and may contribute to immune evasion. IMPORTANCE: This study reveals conformational and antigenic differences between the Delta123 and intact E2661 glycoproteins and provides new structural and functional data about the three variable regions and their role in occluding neutralizing and nonneutralizing epitopes on the E2 core domain. The variable regions may therefore function to reduce the ability of HCV to elicit NAbs directed toward the conserved core domain. Future studies aimed at generating a three-dimensional structure for intact E2 containing HVR1, and the adjoining NAb epitope at residues 412 to 428, together with HVR2, will reveal how the variable regions modulate antigenic structure. PMID- 26378184 TI - Empirical Derivation of Correction Factors for Human Spiral Ganglion Cell Nucleus and Nucleolus Count Units. AB - OBJECTIVE: Profile count method for estimating cell number in sectioned tissue applies a correction factor for double count (resulting from transection during sectioning) of count units selected to represent the cell. For human spiral ganglion cell counts, we attempted to address apparent confusion between published correction factors for nucleus and nucleolus count units that are identical despite the role of count unit diameter in a commonly used correction factor formula. STUDY DESIGN: We examined a portion of human cochlea to empirically derive correction factors for the 2 count units, using 3-dimensional reconstruction software to identify double counts. SETTING: The Neurotology and House Histological Temporal Bone Laboratory at University of California at Los Angeles. SUBJECTS AND METHODS: Using a fully sectioned and stained human temporal bone, we identified and generated digital images of sections of the modiolar region of the lower first turn of cochlea, identified count units with a light microscope, labeled them on corresponding digital sections, and used 3 dimensional reconstruction software to identify double-counted count units. RESULTS: For 25 consecutive sections, we determined that double-count correction factors for nucleus count unit (0.91) and nucleolus count unit (0.92) matched the published factors. We discovered that nuclei and, therefore, spiral ganglion cells were undercounted by 6.3% when using nucleolus count units. CONCLUSION: We determined that correction factors for count units must include an element for undercounting spiral ganglion cells as well as the double-count element. We recommend a correction factor of 0.91 for the nucleus count unit and 0.98 for the nucleolus count unit when using 20-um sections. PMID- 26378183 TI - Abnormal Sleep Duration Is Associated with a Higher Risk of Accidental Injury. AB - OBJECTIVE: Develop normative data for adult sleep duration and determine if nonstandard sleep time relates to the likelihood of accidental injury. STUDY DESIGN: Cross-sectional analysis. SETTING: National health information database. METHODS: The National Health Interview Survey, 2004-2013, was examined for adult sleep time and accidental injury within the past 3 months. The mean hours slept per night was determined. The relationship between sleep time and incidence of accidental injury was determined for any injury, injury while driving, and injury while working, adjusting for demographic variables. RESULTS: Among 221.4 million adults (raw sample, N = 282,692), the mean sleep time was 7.17 hours (95% confidence interval [95% CI], 7.16-7.18 hours). Men and women slept very similar times (7.14 vs 7.17 hours, respectively), and sleep time decreased until the fifth decade (minimum, 6.99 hours), increasing each decade thereafter; 2.81% of adults reported being accidentally injured in the preceding 3 months. Too little sleep and excessive sleep times were both associated with higher rates of accidental injury (odds ratio per hour of deviation from mean, 1.16 [95% CI, 1.12 1.19]), adjusting for age, sex, marital status, and education level. Similar increased odds ratios were noted for injury while driving (1.11 [95% CI, 1.01 1.22]) and injury while at work (1.12 [95% CI, 1.04-1.20]) with sleep time deviation. CONCLUSION: Most adults sleep between 7 and 8 hours nightly. Adults with sleep time outside this range, with either less or more sleep, have increased rates of accidental injury. These data highlight the need for sufficient quantity and quality of sleep in preventing accidental injury. PMID- 26378185 TI - Minimally Invasive Removal of Mandibular Hardware after Free Flap Reconstruction. PMID- 26378186 TI - The Effects of Preoperative Embolization on Carotid Body Paraganglioma Surgery: A Systematic Review and Meta-analysis. AB - OBJECTIVE: There is no definitive consensus on the impact of preoperative embolization on carotid body paraganglioma management. The purpose of this study was to assess the effects of preoperative embolization on carotid body paraganglioma excision. DATA SOURCES: A systematic search was conducted without limits, and it included studies published on or before July 2013 from PubMed, CINAHL, Web of Knowledge, and the Cochrane Library. Relevant synonyms for the search terms "paraganglioma,""carotid body tumor," and "embolization" were applied. REVIEW METHODS: Studies evaluating patients undergoing surgical intervention with embolization for carotid body tumors were included. Two reviewers independently assessed the titles and abstracts for inclusion and extracted the data. The guidelines set forth by the Cochrane Collaboration were followed in the process of data extraction. Data were pooled with a fixed effects model, and standardized mean difference (SMD) and 95% confidence intervals (95% CIs) are reported. RESULTS: A total of 22 studies (15 nonrandomized studies with a comparator, 7 single-arm studies) were included, enrolling 578 patients with 607 tumors. Patients undergoing preoperative embolization had significantly less estimated blood loss compared with those of surgical excision only (12 studies; 295 tumors; SMD: -0.52; 95% CI: -0.77, -0.28). Patients undergoing preoperative embolization had less operative time compared with that of surgical excision only (6 studies; 174 tumors; SMD: -0.46; 95% CI: -0.77, -0.14). CONCLUSION: Surgical excision with preoperative embolization appears to decrease estimated blood loss and operative time when compared with that without preoperative embolization for carotid body paragangliomas. PMID- 26378187 TI - Ureaplasma parvum and Mycoplasma genitalium are found to be significantly associated with microscopy-confirmed urethritis in a routine genitourinary medicine setting. AB - Inflammation of the urethra defined by an excess of polymorphonuclear leukocytes in the absence of sexually transmitted Chlamydia trachomatis and Neisseria gonorrhoeae is called non-chlamydial non-gonococcal urethritis (NCNGU). Although Mycoplasma genitalium is now recognised as causing a sexually transmitted infection, the clinical significance of the other Mollicute species is less clear. This study used specific real-time quantitative polymerase chain reaction assays to detect and quantify four Mollicute species, M. genitalium, M. hominis, Ureaplasma urealyticum and U. parvum, in urine specimens from men with and without NCNGU. A total of 165 urine specimens from male patients attending a genitourinary medicine clinic were eligible for the study, with microscopy confirmed (>=5 polymorphonuclear leukocytes in urethral swab) NCNGU in 75 (45.5%) and non-confirmed NCNGU in 90 (54.5%). Chi-squared statistical analysis indicated a significantly higher prevalence of U. parvum (17.3% vs. 5.6%; p = 0.03) and M. genitalium (12% vs. 0%; p < 0.001) in NCNGU. In a subset analysis, M. genitalium was also significantly (p = 0.03) higher in men who have sex with men (MSM; 13.5%) compared to non-MSM (3.1%). No significant associations were reported for U. urealyticum and M. hominis In conclusion, this study supports a clinically significant role in NGNCU for both U. parvum and M. genitalium. PMID- 26378189 TI - First case of chancroid in 14 years at the largest STI clinic in Paris, France. AB - We report the first case of chancroid seen at our clinic in 14 years. It was diagnosed by nuclear acid amplification test in a male patient returning from Madagascar. Although the disease is considered on the verge of disappearance even in tropical countries, its real potential for reemergence - due to new strains of Haemophilus ducreyi, underreporting and a lack of widespread use of molecular testing - could be underestimated. PMID- 26378188 TI - HIV prevalence, sexual behaviours and engagement in HIV medical care among an online sample of sexually active MSM in Venezuela. AB - In Venezuela, members of a social and sexual partner networking site for men who have sex with men (MSM) completed an online survey regarding sexual behaviours and HIV medical care. Among the 2851 respondents, self-reported HIV prevalence was 6.6%. Of participants living with HIV, 73.2% reported taking antiretroviral medication and 56.6% reported complete adherence within the past month. Participants living with HIV were more likely to be older (aOR = 1.04 per one year increase in age, 95% CI: 1.02, 1.06) and diagnosed with a sexually transmitted infection in the previous year (aOR 3.26, 95% CI: 2.11, 5.04). These data provide further understanding of the HIV epidemic among MSM in Venezuela, and potential targets for HIV prevention interventions. PMID- 26378190 TI - Routine HIV testing in acute medical admissions in a high prevalence area reduces morbidity and mortality of HIV: a full cycle audit. AB - Late HIV diagnosis in the UK remains a major cause of morbidity and mortality. In line with British HIV Association recommendations, we implemented routine HIV Screening in Croydon University Hospital Acute Medical Unit in London after an audit in 2011 revealed very high levels of late diagnosis. Our re-audit assessed the impact of Acute Medical Unit screening and found that patients identified by screening, compared to those tested due to clinical suspicion of HIV, were significantly less likely to be diagnosed late, had fewer AIDS-defining illnesses and shorter hospital admissions. In addition, screening identified patients who were not in traditional 'high-risk' groups and patients who had defaulted HIV care and who subsequently re-engaged with care. PMID- 26378191 TI - Notification following new positive HIV test results. AB - Client notification of a new HIV diagnosis is critical for timely access to treatment and reduction in behaviours associated with HIV infection. It is also an important input in HIV transmission and disease progression models. We used national, Centers for Disease Control and Prevention-funded HIV testing events data collected through the National HIV Prevention Program Monitoring and Evaluation system to update estimates of the proportion of newly identified HIV positives notified of their status. We compared estimates from 2008 to 2010 across test technologies, settings, and HIV risk groups. In 2010, notification following a positive rapid test was 99.6% compared with 99.3% in 2008. Notification following a positive conventional test was 81.5% in 2010 compared with 80.8% in 2008. To realise the full promise of early HIV diagnosis and treatment for the prevention of additional HIV cases, efforts to ensure prompt notification following a new HIV diagnosis will be crucial. PMID- 26378192 TI - Reactive arthritis at the Sydney Sexual Health Centre 1992-2012: declining despite increasing chlamydia diagnoses. AB - Reactive arthritis is an under-studied complication of genital Chlamydia trachomatis infection (chlamydia). We assessed trends and risk factors for reactive arthritis in a large urban sexual health clinic. Using a case-control design, data on reactive arthritis cases and controls at the Sydney Sexual Health Centre over the period 1992-2012 were extracted and multivariate analyses were performed. Trend analyses were performed on reactive arthritis diagnoses. Over the 1992-2012 study period, 85 reactive arthritis cases were diagnosed at Sydney Sexual Health Centre. The rate of reactive arthritis diagnoses decreased over time (23 in 1992-1996 to one in 2007-2011 and none in 2012), while chlamydia diagnoses increased (770 in 1992-1996 to 2257 in 2007-2011). In multivariate analysis, factors independently associated with a reactive arthritis diagnosis were: being male (adjusted odds ratio [aOR] 3.27; 95% confidence interval [CI] 1.04-10.32; p = 0.043) or born overseas (aOR 2.69; 95% CI 1.27-5.70; p = 0.010), while a past sexually transmitted infection other than chlamydia or non gonococcal urethritis was protective (aOR 0.21; 95% CI 0.10-0.45; p < 0.001). Reactive arthritis was not associated with current or recent chlamydia infection (p = 0.184) but was marginally associated with past non-gonococcal urethritis (p = 0.080). This study found a decline in reactive arthritis diagnoses despite an increase in chlamydia diagnoses. PMID- 26378193 TI - Administration of tenofovir disoproxil fumarate-based antiretroviral therapy in an HIV-infected patient following unilateral nephrectomy. AB - We report the use of efavirenz 600 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg, once daily in a 47-year-old black man with a solitary kidney and human immunodeficiency virus (HIV). In 1990, he underwent radiation, chemotherapy, and ultimately, a unilateral nephrectomy for Wilms' tumor. Because of previous reports of tenofovir disoproxil fumarate-induced nephrotoxicity, our objective was to evaluate and monitor our patient's renal function over the course of 19 months based on serum creatinine, estimated creatinine clearance using the Cockroft-Gault equation, estimated glomerular filtration rate using the modification of diet in renal disease formula and urinalyses. After experiencing gastrointestinal side effects from other antiretroviral agents, our patient was switched to efavirenz/emtricitabine/tenofovir disoproxil fumarate in June 2013. At baseline, his serum creatinine was 1.35 mg/dL, estimated creatinine clearance 68.7 mL/min (based on actual body weight of 71.8 kg), estimated glomerular filtration rate 72.9 mL/min/1.73 m(2), with a CD4 cell count of 119 cells/mm(3) (5%) and an undetectable HIV viral load. In March 2015, his weight was 73.2 kg, serum creatinine 1.42 mg/dL, estimated creatinine clearance 65.2 mL/min, estimated glomerular filtration rate 68.1 mL/min/1.73 m(2), with a CD4 cell count of 120 cells/mm(3) (10%) and an undetectable HIV viral load. Other authors have reported tenofovir-induced nephrotoxicity in patients with a solitary kidney. Our patient had no evidence of nephrotoxicity over the course of 19 months on tenofovir disoproxil fumarate-based antiretroviral therapy (ART). He maintained adequate renal function, comparable to his baseline renal function. Our case report suggests that a tenofovir disoproxil fumurate-based ART may be a viable option for some patients with a solitary kidney. Additional studies and data are needed considering this is a small and relatively unstudied population. PMID- 26378194 TI - Point-of-care testing for HIV in an Irish prison setting: results from three major Irish prisons. AB - HIV is more prevalent in the prison population compared to the general population. Prison inmates are at an increased risk of blood-borne infections. Considerable stigma has been documented amongst inmates with HIV infection. In collaboration with the schools, healthcare facilities, prison authorities and inmate Irish Red Cross groups in Wheatfield, Cloverhill and Mountjoy prisons in Dublin, Ireland, the Department of Genito Urinary Medicine and Infectious Diseases at St James' Hospital in Dublin developed a campaign for raising awareness of HIV, educating inmates about HIV and tackling HIV stigma. Following this campaign, large-scale point-of-care testing for HIV was offered over a short period. In total, 741 inmates were screened for HIV. One inmate tested positive for HIV. We experienced a large number of invalid test results, requiring formal laboratory serum testing, and a small number of false positive results. Large scale point-of-care testing in the Irish prison setting is acceptable and achievable. PMID- 26378195 TI - Energy Implications of Consuming Caffeinated Versus Decaffeinated Energy Drinks. PMID- 26378196 TI - Presidential Address: Adding Value to Professional Organizations. PMID- 26378198 TI - Get the facts right: time for evidence-based ethics. PMID- 26378199 TI - Neuromuscular adjustments of gait associated with unstable conditions. AB - A compact description of coordinated muscle activity is provided by the factorization of electromyographic (EMG) signals. With the use of this approach, it has consistently been shown that multimuscle activity during human locomotion can be accounted for by four to five modules, each one comprised of a basic pattern timed at a different phase of gait cycle and the weighting coefficients of synergistic muscle activations. These modules are flexible, in so far as the timing of patterns and the amplitude of weightings can change as a function of gait speed and mode. Here we consider the adjustments of the locomotor modules related to unstable walking conditions. We compared three different conditions, i.e., locomotion of healthy subjects on slippery ground (SL) and on narrow beam (NB) and of cerebellar ataxic (CA) patients on normal ground. Motor modules were computed from the EMG signals of 12 muscles of the right lower limb using non negative matrix factorization. The unstable gait of SL, NB, and CA showed significant changes compared with controls in the stride length, stride width, range of angular motion, and trunk oscillations. In most subjects of all three unstable conditions, >70% of the overall variation of EMG waveforms was accounted for by four modules that were characterized by a widening of muscle activity patterns. This suggests that the nervous system adopts the strategy of prolonging the duration of basic muscle activity patterns to cope with unstable conditions resulting from either slippery ground, reduced support surface, or pathology. PMID- 26378200 TI - Two types of local interneurons are distinguished by morphology, intrinsic membrane properties, and functional connectivity in the moth antennal lobe. AB - Neurons in the silkmoth antennal lobe (AL) are well characterized in terms of their morphology and odor-evoked firing activity. However, their intrinsic electrical properties including voltage-gated ionic currents and synaptic connectivity remain unclear. To address this, whole cell current- and voltage clamp recordings were made from second-order projection neurons (PNs) and two morphological types of local interneurons (LNs) in the silkmoth AL. The two morphological types of LNs exhibited distinct physiological properties. One morphological type of LN showed a spiking response with a voltage-gated sodium channel gene expression, whereas the other type of LN was nonspiking without a voltage-gated sodium channel gene expression. Voltage-clamp experiments also revealed that both of two types of LNs as well as PNs possessed two types of voltage-gated potassium channels and calcium channels. In dual whole cell recordings of spiking LNs and PNs, activation of the PN elicited depolarization responses in the paired spiking LN, whereas activation of the spiking LN induced no substantial responses in the paired PN. However, simultaneous recording of a nonspiking LN and a PN showed that activation of the nonspiking LN induced hyperpolarization responses in the PN. We also observed bidirectional synaptic transmission via both chemical and electrical coupling in the pairs of spiking LNs. Thus our results indicate that there were two distinct types of LNs in the silkmoth AL, and their functional connectivity to PNs was substantially different. We propose distinct functional roles for these two different types of LNs in shaping odor-evoked firing activity in PNs. PMID- 26378201 TI - Discrete coding of stimulus value, reward expectation, and reward prediction error in the dorsal striatum. AB - To investigate how the striatum integrates sensory information with reward information for behavioral guidance, we recorded single-unit activity in the dorsal striatum of head-fixed rats participating in a probabilistic Pavlovian conditioning task with auditory conditioned stimuli (CSs) in which reward probability was fixed for each CS but parametrically varied across CSs. We found that the activity of many neurons was linearly correlated with the reward probability indicated by the CSs. The recorded neurons could be classified according to their firing patterns into functional subtypes coding reward probability in different forms such as stimulus value, reward expectation, and reward prediction error. These results suggest that several functional subgroups of dorsal striatal neurons represent different kinds of information formed through extensive prior exposure to CS-reward contingencies. PMID- 26378202 TI - A neuronal reward inequity signal in primate striatum. AB - Primates are social animals, and their survival depends on social interactions with others. Especially important for social interactions and welfare is the observation of rewards obtained by other individuals and the comparison with own reward. The fundamental social decision variable for the comparison process is reward inequity, defined by an asymmetric reward distribution among individuals. An important brain structure for coding reward inequity may be the striatum, a component of the basal ganglia involved in goal-directed behavior. Two rhesus monkeys were seated opposite each other and contacted a touch-sensitive table placed between them to obtain specific magnitudes of reward that were equally or unequally distributed among them. Response times in one of the animals demonstrated differential behavioral sensitivity to reward inequity. A group of neurons in the striatum showed distinct signals reflecting disadvantageous and advantageous reward inequity. These neuronal signals occurred irrespective of, or in conjunction with, own reward coding. These data demonstrate that striatal neurons of macaque monkeys sense the differences between other's and own reward. The neuronal activities are likely to contribute crucial reward information to neuronal mechanisms involved in social interactions. PMID- 26378203 TI - Insights into decision making using choice probability. AB - A long-standing question in systems neuroscience is how the activity of single neurons gives rise to our perceptions and actions. Critical insights into this question occurred in the last part of the 20th century when scientists began linking modulations of neuronal activity directly to perceptual behavior. A significant conceptual advance was the application of signal detection theory to both neuronal activity and behavior, providing a quantitative assessment of the relationship between brain and behavior. One metric that emerged from these efforts was choice probability (CP), which provides information about how well an ideal observer can predict the choice an animal makes from a neuron's discharge rate distribution. In this review, we describe where CP has been studied, locational trends in the values found, and why CP values are typically so low. We discuss its dependence on correlated activity among neurons of a population, assess whether it arises from feedforward or feedback mechanisms, and investigate what CP tells us about how many neurons are required for a decision and how they are pooled to do so. PMID- 26378205 TI - Spatial phase sensitivity of complex cells in primary visual cortex depends on stimulus contrast. AB - Neurons in primary visual cortex are classified as simple, which are phase sensitive, or complex, which are significantly less phase sensitive. Previously, we have used drifting gratings to show that the phase sensitivity of complex cells increases at low contrast and after contrast adaptation while that of simple cells remains the same at all contrasts (Cloherty SL, Ibbotson MR. J Neurophysiol 113: 434-444, 2015; Crowder NA, van Kleef J, Dreher B, Ibbotson MR. J Neurophysiol 98: 1155-1166, 2007; van Kleef JP, Cloherty SL, Ibbotson MR. J Physiol 588: 3457-3470, 2010). However, drifting gratings confound the influence of spatial and temporal summation, so here we have stimulated complex cells with gratings that are spatially stationary but continuously reverse the polarity of the contrast over time (contrast-reversing gratings). By varying the spatial phase and contrast of the gratings we aimed to establish whether the contrast dependent phase sensitivity of complex cells results from changes in spatial or temporal processing or both. We found that most of the increase in phase sensitivity at low contrasts could be attributed to changes in the spatial phase sensitivities of complex cells. However, at low contrasts the complex cells did not develop the spatiotemporal response characteristics of simple cells, in which paired response peaks occur 180 degrees out of phase in time and space. Complex cells that increased their spatial phase sensitivity at low contrasts were significantly overrepresented in the supragranular layers of cortex. We conclude that complex cells in supragranular layers of cat cortex have dynamic spatial summation properties and that the mechanisms underlying complex cell receptive fields differ between cortical layers. PMID- 26378204 TI - Automatic reconstruction of physiological gestures used in a model of birdsong production. AB - Highly coordinated learned behaviors are key to understanding neural processes integrating the body and the environment. Birdsong production is a widely studied example of such behavior in which numerous thoracic muscles control respiratory inspiration and expiration: the muscles of the syrinx control syringeal membrane tension, while upper vocal tract morphology controls resonances that modulate the vocal system output. All these muscles have to be coordinated in precise sequences to generate the elaborate vocalizations that characterize an individual's song. Previously we used a low-dimensional description of the biomechanics of birdsong production to investigate the associated neural codes, an approach that complements traditional spectrographic analysis. The prior study used algorithmic yet manual procedures to model singing behavior. In the present work, we present an automatic procedure to extract low-dimensional motor gestures that could predict vocal behavior. We recorded zebra finch songs and generated synthetic copies automatically, using a biomechanical model for the vocal apparatus and vocal tract. This dynamical model described song as a sequence of physiological parameters the birds control during singing. To validate this procedure, we recorded electrophysiological activity of the telencephalic nucleus HVC. HVC neurons were highly selective to the auditory presentation of the bird's own song (BOS) and gave similar selective responses to the automatically generated synthetic model of song (AUTO). Our results demonstrate meaningful dimensionality reduction in terms of physiological parameters that individual birds could actually control. Furthermore, this methodology can be extended to other vocal systems to study fine motor control. PMID- 26378206 TI - Adaptation-induced modification of motion selectivity tuning in visual tectal neurons of adult zebrafish. AB - In the developing brain, training-induced emergence of direction selectivity and plasticity of orientation tuning appear to be widespread phenomena. These are found in the visual pathway across different classes of vertebrates. Moreover, short-term plasticity of orientation tuning in the adult brain has been demonstrated in several species of mammals. However, it is unclear whether neuronal orientation and direction selectivity in nonmammalian species remains modifiable through short-term plasticity in the fully developed brain. To address this question, we analyzed motion tuning of neurons in the optic tectum of adult zebrafish by calcium imaging. In total, orientation and direction selectivity was enhanced by adaptation, responses of previously orientation-selective neurons were sharpened, and even adaptation-induced emergence of selectivity in previously nonselective neurons was observed in some cases. The different observed effects are mainly based on the relative distance between the previously preferred and the adaptation direction. In those neurons in which a shift of the preferred orientation or direction was induced by adaptation, repulsive shifts (i.e., away from the adapter) were more prevalent than attractive shifts. A further novel finding for visually induced adaptation that emerged from our study was that repulsive and attractive shifts can occur within one brain area, even with uniform stimuli. The type of shift being induced also depends on the difference between the adapting and the initially preferred stimulus direction. Our data indicate that, even within the fully developed optic tectum, short-term plasticity might have an important role in adjusting neuronal tuning functions to current stimulus conditions. PMID- 26378207 TI - Common drive to the upper airway muscle genioglossus during inspiratory loading. AB - Common drive is thought to constitute a central mechanism by which the efficiency of a motor neuron pool is increased. This study tested the hypothesis that common drive to the upper airway muscle genioglossus (GG) would increase with increased respiratory drive in response to an inspiratory load. Respiration, GG electromyographic (EMG) activity, single-motor unit activity, and coherence in the 0-5 Hz range between pairs of GG motor units were assessed for the 30 s before an inspiratory load, the first and second 30 s of the load, and the 30 s after the load. Twelve of twenty young, healthy male subjects provided usable data, yielding 77 pairs of motor units: 2 Inspiratory Phasic, 39 Inspiratory Tonic, 15 Expiratory Tonic, and 21 Tonic. Respiratory and GG inspiratory activity significantly increased during the loads and returned to preload levels during the postload periods (all showed significant quadratic functions over load trials, P < 0.05). As hypothesized, common drive increased during the load in inspiratory modulated motor units to a greater extent than in expiratory/tonic motor units (significant load * discharge pattern interaction, P < 0.05). Furthermore, this effect persisted during the postload period. In conclusion, common drive to inspiratory modulated motor units was elevated in response to increased respiratory drive. The postload elevation in common drive was suggestive of a poststimulus activation effect. PMID- 26378208 TI - Dynamics of visual receptive fields in the macaque frontal eye field. AB - Neuronal receptive fields (RFs) provide the foundation for understanding systems level sensory processing. In early visual areas, investigators have mapped RFs in detail using stochastic stimuli and sophisticated analytical approaches. Much less is known about RFs in prefrontal cortex. Visual stimuli used for mapping RFs in prefrontal cortex tend to cover a small range of spatial and temporal parameters, making it difficult to understand their role in visual processing. To address these shortcomings, we implemented a generalized linear model to measure the RFs of neurons in the macaque frontal eye field (FEF) in response to sparse, full-field stimuli. Our high-resolution, probabilistic approach tracked the evolution of RFs during passive fixation, and we validated our results against conventional measures. We found that FEF neurons exhibited a surprising level of sensitivity to stimuli presented as briefly as 10 ms or to multiple dots presented simultaneously, suggesting that FEF visual responses are more precise than previously appreciated. FEF RF spatial structures were largely maintained over time and between stimulus conditions. Our results demonstrate that the application of probabilistic RF mapping to FEF and similar association areas is an important tool for clarifying the neuronal mechanisms of cognition. PMID- 26378209 TI - Cell swelling increases the severity of spreading depression in Locusta migratoria. AB - Progressive accumulation of extracellular potassium ions can trigger propagating waves of spreading depression (SD), which are associated with dramatic increases in extracellular potassium levels ([K(+)]o) and arrest in neural activity. In the central nervous system the restricted nature of the extracellular compartment creates an environment that is vulnerable to disturbances in ionic homeostasis. Here we investigate how changes in the size of the extracellular space induced by alterations in extracellular osmolarity affect locust SD. We found that hypotonic exposure increased susceptibility to experimentally induced SD evidenced by a decrease in the latency to onset and period between individual events. Hypertonic exposure was observed to delay the onset of SD or prevent the occurrence altogether. Additionally, the magnitude of extracellular K(+) concentration ([K(+)]o) disturbance during individual SD events was significantly greater and they were observed to propagate more quickly under hypotonic conditions compared with hypertonic conditions. Our results are consistent with a conclusion that hypotonic exposure reduced the size of the extracellular compartment by causing cell swelling and thus facilitated the accumulation of K(+) ions. Lastly, we found that pharmacologically reducing the accumulation of extracellular K(+) using the K(+) channel blocker tetraethylammonium slowed the rate of SD propagation while increasing [K(+)]o through inhibition of the Na-K-2Cl cotransporter increased propagation rates. Overall our findings indicate that treatments or conditions that act to reduce the accumulation of extracellular K(+) help to protect against the development of SD and attenuate the spread of ionic disturbance adding to the evidence that diffusion of K(+) is a leading event during locust SD. PMID- 26378210 TI - Layer-specific modulation of entorhinal cortical excitability by presubiculum in a rat model of temporal lobe epilepsy. AB - Temporal lobe epilepsy (TLE) is the most common form of epilepsy in adults and is often refractory to antiepileptic medications. The medial entorhinal area (MEA) is affected in TLE but mechanisms underlying hyperexcitability of MEA neurons require further elucidation. Previous studies suggest that inputs from the presubiculum (PrS) contribute to MEA pathophysiology. We assessed electrophysiologically how PrS influences MEA excitability using the rat pilocarpine model of TLE. PrS-MEA connectivity was confirmed by electrically stimulating PrS afferents while recording from neurons within superficial layers of MEA. Assessment of alterations in PrS-mediated synaptic drive to MEA neurons was made following focal application of either glutamate or NBQX to the PrS in control and epileptic animals. Here, we report that monosynaptic inputs to MEA from PrS neurons are conserved in epileptic rats, and that PrS modulation of MEA excitability is layer-specific. PrS contributes more to synaptic inhibition of LII stellate cells than excitation. Under epileptic conditions, stellate cell inhibition is significantly reduced while excitatory synaptic drive is maintained at levels similar to control. PrS contributes to both synaptic excitation and inhibition of LIII pyramidal cells in control animals. Under epileptic conditions, overall excitatory synaptic drive to these neurons is enhanced while inhibitory synaptic drive is maintained at control levels. Additionally, neither glutamate nor NBQX applied focally to PrS now affected EPSC and IPSC frequency of LIII pyramidal neurons. These layer-specific changes in PrS-MEA interactions are unexpected and of significance in unraveling pathophysiological mechanisms underlying TLE. PMID- 26378211 TI - Factor Xa inhibitors: a novel therapeutic class for the treatment of nonvalvular atrial fibrillation. AB - Atrial fibrillation is the most common cause of stroke. Treatment with anticoagulants in patients with atrial fibrillation reduces embolic complications of the disease including stroke. However, the commonly used anticoagulant has a narrow therapeutic index, requires routine monitoring, and has numerous drug and food interactions leading to less than optimal rates of adherence. Inhibition of clotting factor Xa has been evaluated as a potential target for anticoagulation therapy with the hypothesis that using target-specific therapy will alleviate some of the dosing variability observed with the vitamin K antagonist. Three factor Xa inhibitors are currently indicated for use in nonvalvular atrial fibrillation. Similar to the vitamin K antagonist, warfarin, all of the factor Xa inhibitors are administered orally. Rivaroxaban and edoxaban are dosed once daily while apixaban is dosed twice daily. All three agents have demonstrated noninferiority when compared with current standard treatment with warfarin for efficacy and safety outcomes. The therapeutic dose of factor Xa inhibitors vary based on renal function. Unlike warfarin, there are no currently available antidotes for the factor Xa inhibitors although this is an area of interest for current and future studies. In the event of a life-threatening bleed there are established management strategies to reverse the bleeding effects of the factor Xa inhibitors. PMID- 26378212 TI - Size structures sensory hierarchy in ocean life. AB - Survival in aquatic environments requires organisms to have effective means of collecting information from their surroundings through various sensing strategies. In this study, we explore how sensing mode and range depend on body size. We find a hierarchy of sensing modes determined by body size. With increasing body size, a larger battery of modes becomes available (chemosensing, mechanosensing, vision, hearing and echolocation, in that order) while the sensing range also increases. This size-dependent hierarchy and the transitions between primary sensory modes are explained on the grounds of limiting factors set by physiology and the physical laws governing signal generation, transmission and reception. We theoretically predict the body size limits for various sensory modes, which align well with size ranges found in literature. The treatise of all ocean life, from unicellular organisms to whales, demonstrates how body size determines available sensing modes, and thereby acts as a major structuring factor of aquatic life. PMID- 26378213 TI - Saturating effects of species diversity on life-history evolution in bacteria. AB - Species interactions can play a major role in shaping evolution in new environments. In theory, species interactions can either stimulate evolution by promoting coevolution or inhibit evolution by constraining ecological opportunity. The relative strength of these effects should vary as species richness increases, and yet there has been little evidence for evolution of component species in communities. We evolved bacterial microcosms containing between 1 and 12 species in three different environments. Growth rates and yields of isolates that evolved in communities were lower than those that evolved in monocultures, consistent with recent theory that competition constrains species to specialize on narrower sets of resources. This effect saturated or reversed at higher levels of richness, consistent with theory that directional effects of species interactions should weaken in more diverse communities. Species varied considerably, however, in their responses to both environment and richness levels. Mechanistic models and experiments are now needed to understand and predict joint evolutionary dynamics of species in diverse communities. PMID- 26378214 TI - Quantifying uncertainty in the phylogenetics of Australian numeral systems. AB - Researchers have long been interested in the evolution of culture and the ways in which change in cultural systems can be reconstructed and tracked. Within the realm of language, these questions are increasingly investigated with Bayesian phylogenetic methods. However, such work in cultural phylogenetics could be improved by more explicit quantification of reconstruction and transition probabilities. We apply such methods to numerals in the languages of Australia. As a large phylogeny with almost universal 'low-limit' systems, Australian languages are ideal for investigating numeral change over time. We reconstruct the most likely extent of the system at the root and use that information to explore the ways numerals evolve. We show that these systems do not increment serially, but most commonly vary their upper limits between 3 and 5. While there is evidence for rapid system elaboration beyond the lower limits, languages lose numerals as well as gain them. We investigate the ways larger numerals build on smaller bases, and show that there is a general tendency to both gain and replace 4 by combining 2 + 2 (rather than inventing a new unanalysable word 'four'). We develop a series of methods for quantifying and visualizing the results. PMID- 26378215 TI - Feeder use predicts both acquisition and transmission of a contagious pathogen in a North American songbird. AB - Individual heterogeneity can influence the dynamics of infectious diseases in wildlife and humans alike. Thus, recent work has sought to identify behavioural characteristics that contribute disproportionately to individual variation in pathogen acquisition (super-receiving) or transmission (super-spreading). However, it remains unknown whether the same behaviours enhance both acquisition and transmission, a scenario likely to result in explosive epidemics. Here, we examined this possibility in an ecologically relevant host-pathogen system: house finches and their bacterial pathogen, Mycoplasma gallisepticum, which causes severe conjunctivitis. We examined behaviours likely to influence disease acquisition (feeder use, aggression, social network affiliations) in an observational field study, finding that the time an individual spends on bird feeders best predicted the risk of conjunctivitis. To test whether this behaviour also influences the likelihood of transmitting M. gallisepticum, we experimentally inoculated individuals based on feeding behaviour and tracked epidemics within captive flocks. As predicted, transmission was fastest when birds that spent the most time on feeders initiated the epidemic. Our results suggest that the same behaviour underlies both pathogen acquisition and transmission in this system and potentially others. Identifying individuals that exhibit such behaviours is critical for disease management. PMID- 26378216 TI - Heterospecific aggression bias towards a rarer colour morph. AB - Colour polymorphisms are a striking example of phenotypic diversity, yet the sources of selection that allow different morphs to persist within populations remain poorly understood. In particular, despite the importance of aggression in mediating social dominance, few studies have considered how heterospecific aggression might contribute to the maintenance or divergence of different colour morphs. To redress this gap, we carried out a field-based study in a Nicaraguan crater lake to investigate patterns of heterospecific aggression directed by the cichlid fish, Hypsophrys nicaraguensis, towards colour polymorphic cichlids in the genus Amphilophus. We found that H. nicaraguensis was the most frequent territorial neighbour of the colour polymorphic A. sagittae. Furthermore, when manipulating territorial intrusions using models, H. nicaraguensis were more aggressive towards the gold than dark colour morph of the sympatric Amphilophus species, including A. sagittae. Such a pattern of heterospecific aggression should be costly to the gold colour morph, potentially accounting for its lower than expected frequency and, more generally, highlighting the importance of considering heterospecific aggression in the context of morph frequencies and coexistence in the wild. PMID- 26378217 TI - In a warmer Arctic, mosquitoes avoid increased mortality from predators by growing faster. AB - Climate change is altering environmental temperature, a factor that influences ectothermic organisms by controlling rates of physiological processes. Demographic effects of warming, however, are determined by the expression of these physiological effects through predator-prey and other species interactions. Using field observations and controlled experiments, we measured how increasing temperatures in the Arctic affected development rates and mortality rates (from predation) of immature Arctic mosquitoes in western Greenland. We then developed and parametrized a demographic model to evaluate how temperature affects survival of mosquitoes from the immature to the adult stage. Our studies showed that warming increased development rate of immature mosquitoes (Q10 = 2.8) but also increased daily mortality from increased predation rates by a dytiscid beetle (Q10 = 1.2-1.5). Despite increased daily mortality, the model indicated that faster development and fewer days exposed to predators resulted in an increased probability of mosquito survival to the adult stage. Warming also advanced mosquito phenology, bringing mosquitoes into phenological synchrony with caribou. Increases in biting pests will have negative consequences for caribou and their role as a subsistence resource for local communities. Generalizable frameworks that account for multiple effects of temperature are needed to understand how climate change impacts coupled human-natural systems. PMID- 26378218 TI - Adult sex ratio, sexual dimorphism and sexual selection in a Mesozoic reptile. AB - The evolutionary history of sexual selection in the geologic past is poorly documented based on quantification, largely because of difficulty in sexing fossil specimens. Even such essential ecological parameters as adult sex ratio (ASR) and sexual size dimorphism (SSD) are rarely quantified, despite their implications for sexual selection. To enable their estimation, we propose a method for unbiased sex identification based on sexual shape dimorphism, using size-independent principal components of phenotypic data. We applied the method to test sexual selection in Keichousaurus hui, a Middle Triassic (about 237 Ma) sauropterygian with an unusually large sample size for a fossil reptile. Keichousaurus hui exhibited SSD biased towards males, as in the majority of extant reptiles, to a minor degree (sexual dimorphism index -0.087). The ASR is about 60% females, suggesting higher mortality of males over females. Both values support sexual selection of males in this species. The method may be applied to other fossil species. We also used the Gompertz allometric equation to study the sexual shape dimorphism of K. hui and found that two sexes had largely homogeneous phenotypes at birth except in the humeral width, contrary to previous suggestions derived from the standard allometric equation. PMID- 26378219 TI - Genetic perturbation of key central metabolic genes extends lifespan in Drosophila and affects response to dietary restriction. AB - There is a connection between nutrient inputs, energy-sensing pathways, lifespan variation and aging. Despite the role of metabolic enzymes in energy homeostasis and their metabolites as nutrient signals, little is known about how their gene expression impacts lifespan. In this report, we use P-element mutagenesis in Drosophila to study the effect on lifespan of reductions in expression of seven central metabolic enzymes, and contrast the effects on normal diet and dietary restriction. The major observation is that for five of seven genes, the reduction of gene expression extends lifespan on one or both diets. Two genes are involved in redox balance, and we observe that lower activity genotypes significantly extend lifespan. The hexokinases also show extension of lifespan with reduced gene activity. Since both affect the ATP/ADP ratio, this connects with the role of AMP-activated protein kinase as an energy sensor in regulating lifespan and mediating caloric restriction. These genes possess significant expression variation in natural populations, and our experimental genotypes span this level of natural activity variation. Our studies link the readout of energy state with the perturbation of the genes of central metabolism and demonstrate their effect on lifespan. PMID- 26378220 TI - Adaptation to different host plant ages facilitates insect divergence without a host shift. AB - Host shifts and subsequent adaption to novel host plants are important drivers of speciation among phytophagous insects. However, there is considerably less evidence for host plant-mediated speciation in the absence of a host shift. Here, we investigated divergence of two sympatric sister elm leaf beetles, Pyrrhalta maculicollis and P. aenescens, which feed on different age classes of the elm Ulmus pumila L. (seedling versus adult trees). Using a field survey coupled with preference and performance trials, we show that these beetle species are highly divergent in both feeding and oviposition preference and specialize on either seedling or adult stages of their host plant. An experiment using artificial leaf discs painted with leaf surface wax extracts showed that host plant chemistry is a critical element that shapes preference. Specialization appears to be driven by adaptive divergence as there was also evidence of divergent selection; beetles had significantly higher survival and fecundity when reared on their natal host plant age class. Together, the results identify the first probable example of divergence induced by host plant age, thus extending how phytophagous insects might diversify in the absence of host shifts. PMID- 26378221 TI - Mitonuclear linkage disequilibrium in human populations. AB - There is extensive evidence from model systems that disrupting associations between co-adapted mitochondrial and nuclear genotypes can lead to deleterious and even lethal consequences. While it is tempting to extrapolate from these observations and make inferences about the human-health effects of altering mitonuclear associations, the importance of such associations may vary greatly among species, depending on population genetics, demographic history and other factors. Remarkably, despite the extensive study of human population genetics, the statistical associations between nuclear and mitochondrial alleles remain largely uninvestigated. We analysed published population genomic data to test for signatures of historical selection to maintain mitonuclear associations, particularly those involving nuclear genes that encode mitochondrial-localized proteins (N-mt genes). We found that significant mitonuclear linkage disequilibrium (LD) exists throughout the human genome, but these associations were generally weak, which is consistent with the paucity of population genetic structure in humans. Although mitonuclear LD varied among genomic regions (with especially high levels on the X chromosome), N-mt genes were statistically indistinguishable from background levels, suggesting that selection on mitonuclear epistasis has not preferentially maintained associations involving this set of loci at a species-wide level. We discuss these findings in the context of the ongoing debate over mitochondrial replacement therapy. PMID- 26378222 TI - Normal vision can compensate for the loss of the circadian clock. AB - Circadian clocks are thought to be essential for timing the daily activity of animals, and consequently increase fitness. This view was recently challenged for clock-less fruit flies and mice that exhibited astonishingly normal activity rhythms under outdoor conditions. Compensatory mechanisms appear to enable even clock mutants to live a normal life in nature. Here, we show that gradual daily increases/decreases of light in the laboratory suffice to provoke normally timed sharp morning (M) and evening (E) activity peaks in clock-less flies. We also show that the compound eyes, but not Cryptochrome (CRY), mediate the precise timing of M and E peaks under natural-like conditions, as CRY-less flies do and eyeless flies do not show these sharp peaks independently of a functional clock. Nevertheless, the circadian clock appears critical for anticipating dusk, as well as for inhibiting sharp activity peaks during midnight. Clock-less flies only increase E activity after dusk and not before the beginning of dusk, and respond strongly to twilight exposure in the middle of the night. Furthermore, the circadian clock responds to natural-like light cycles, by slightly broadening Timeless (TIM) abundance in the clock neurons, and this effect is mediated by CRY. PMID- 26378225 TI - GENERALISATION OF RADIATOR DESIGN TECHNIQUES FOR PERSONAL NEUTRON DOSEMETERS BY UNFOLDING METHOD. AB - A novel technique for designing a radiator suitable for personal neutron dosemeter based on plastic track detector was discussed. A multi-layer structure has been proposed in the previous report, where the thicknesses of plural polyethylene (PE) layers and insensitive ones were determined by iterative calculations of double integral. In order to arrange this procedure and make it more systematic, unfolding calculation has been employed to estimate an ideal radiator containing an arbitrary hydrogen concentration. In the second step, realistic materials replaced it with consideration of minimisation of the layer number and commercial availability. A radiator consisting of three layers of PE, Upilex and Kapton sheets was finally designed, for which a deviation in the energy dependence between 0.1 and 20 MeV could be controlled within 18 %. An applicability of fluorescent nuclear track detector element has also been discussed. PMID- 26378224 TI - Impact of a Biomarker-Based Strategy on Oncology Drug Development: A Meta analysis of Clinical Trials Leading to FDA Approval. AB - BACKGROUND: In order to ascertain the impact of a biomarker-based (personalized) strategy, we compared outcomes between US Food and Drug Administration (FDA) approved cancer treatments that were studied with and without such a selection rationale. METHODS: Anticancer agents newly approved (September 1998 to June 2013) were identified at the Drugs@FDA website. Efficacy, treatment-related mortality, and hazard ratios (HRs) for time-to-event endpoints were analyzed and compared in registration trials for these agents. All statistical tests were two sided. RESULTS: Fifty-eight drugs were included (leading to 57 randomized [32% personalized] and 55 nonrandomized trials [47% personalized], n = 38 104 patients). Trials adopting a personalized strategy more often included targeted (100% vs 65%, P < .001), oral (68% vs 35%, P = .001), and single agents (89% vs 71%, P = .04) and more frequently permitted crossover to experimental treatment (67% vs 28%, P = .009). In randomized registration trials (using a random-effects meta-analysis), personalized therapy arms were associated with higher relative response rate ratios (RRRs, compared with their corresponding control arms) (RRRs = 3.82, 95% confidence interval [CI] = 2.51 to 5.82, vs RRRs = 2.08, 95% CI = 1.76 to 2.47, adjusted P = .03), longer PFS (hazard ratio [HR] = 0.41, 95% CI = 0.33 to 0.51, vs HR = 0.59, 95% CI = 0.53 to 0.65, adjusted P < .001) and a non statistically significantly longer OS (HR = 0.71, 95% CI = 0.61 to 0.83, vs HR = 0.81, 95% CI = 0.77 to 0.85, adjusted P = .07) compared with nonpersonalized trials. Analysis of experimental arms in all 112 registration trials (randomized and nonrandomized) demonstrated that personalized therapy was associated with higher response rate (48%, 95% CI = 42% to 55%, vs 23%, 95% CI = 20% to 27%, P < .001) and longer PFS (median = 8.3, interquartile range [IQR] = 5 vs 5.5 months, IQR = 5, adjusted P = .002) and OS (median = 19.3, IQR = 17 vs 13.5 months, IQR = 8, Adjusted P = .04). A personalized strategy was an independent predictor of better RR, PFS, and OS, as demonstrated by multilinear regression analysis. Treatment-related mortality rate was similar for personalized and nonpersonalized trials. CONCLUSIONS: A biomarker-based approach was safe and associated with improved efficacy outcomes in FDA-approved anticancer agents. PMID- 26378226 TI - Single ventricle: repair of atrioventricular valve using the bridging technique. AB - Atrioventricular valve regurgitation is one of the predictors of adverse outcomes after the Fontan procedure. We describe our surgical technique of GoreTex (W. L. Gore & Associates, Inc., Flagstaff, AZ, USA) bridge to repair a common atrioventricular valve in single-ventricular circulation. The repair includes a GoreTex strip that is secured to the mid-line of both superior and inferior bridging leaflets and annulus to obtain a better coaptation of the leaflets and prevent further dilatation of the annulus. We have applied this technique for 7 consecutive patients with excellent outcomes. PMID- 26378223 TI - Cell Walls and the Convergent Evolution of the Viral Envelope. AB - Why some viruses are enveloped while others lack an outer lipid bilayer is a major question in viral evolution but one that has received relatively little attention. The viral envelope serves several functions, including protecting the RNA or DNA molecule(s), evading recognition by the immune system, and facilitating virus entry. Despite these commonalities, viral envelopes come in a wide variety of shapes and configurations. The evolution of the viral envelope is made more puzzling by the fact that nonenveloped viruses are able to infect a diverse range of hosts across the tree of life. We reviewed the entry, transmission, and exit pathways of all (101) viral families on the 2013 International Committee on Taxonomy of Viruses (ICTV) list. By doing this, we revealed a strong association between the lack of a viral envelope and the presence of a cell wall in the hosts these viruses infect. We were able to propose a new hypothesis for the existence of enveloped and nonenveloped viruses, in which the latter represent an adaptation to cells surrounded by a cell wall, while the former are an adaptation to animal cells where cell walls are absent. In particular, cell walls inhibit viral entry and exit, as well as viral transport within an organism, all of which are critical waypoints for successful infection and spread. Finally, we discuss how this new model for the origin of the viral envelope impacts our overall understanding of virus evolution. PMID- 26378227 TI - 20-Hydroxyecdysone (20E) Primary Response Gene E93 Modulates 20E Signaling to Promote Bombyx Larval-Pupal Metamorphosis. AB - As revealed in a previous microarray study to identify genes regulated by 20 hydroxyecdysone (20E) and juvenile hormone (JH) in the silkworm, Bombyx mori, E93 expression in the fat body was markedly low prior to the wandering stage but abundant during larval-pupal metamorphosis. Induced by 20E and suppressed by JH, E93 expression follows this developmental profile in multiple silkworm alleles. The reduction of E93 expression by RNAi disrupted 20E signaling and the 20E induced autophagy, caspase activity, and cell dissociation in the fat body. Reducing E93 expression also decreased the expression of the 20E-induced pupal specific cuticle protein genes and prevented growth and differentiation of the wing discs. Importantly, the two HTH domains in E93 are critical for inducing the expression of a subset of 20E response genes, including EcR, USP, E74, Br-C, and Atg1. By contrast, the LLQHLL and PLDLSAK motifs in E93 inhibit its transcriptional activity. E93 binds to the EcR-USP complex via a physical association with USP through its LLQHLL motif; and this association is enhanced by 20E-induced EcR-USP interaction, which attenuates the transcriptional activity of E93. E93 acts through the two HTH domains to bind to GAGA-containing motifs present in the Atg1 promoter region for inducing gene expression. In conclusion, E93 transcriptionally modulates 20E signaling to promote Bombyx larval-pupal metamorphosis. PMID- 26378228 TI - Identification of the ISWI Chromatin Remodeling Complex of the Early Branching Eukaryote Trypanosoma brucei. AB - ISWI chromatin remodelers are highly conserved in eukaryotes and are important for the assembly and spacing of nucleosomes, thereby controlling transcription initiation and elongation. ISWI is typically associated with different subunits, forming specialized complexes with discrete functions. In the unicellular parasite Trypanosoma brucei, which causes African sleeping sickness, TbISWI down regulates RNA polymerase I (Pol I)-transcribed variant surface glycoprotein (VSG) gene expression sites (ESs), which are monoallelically expressed. Here, we use tandem affinity purification to determine the interacting partners of TbISWI. We identify three proteins that do not show significant homology with known ISWI associated partners. Surprisingly, one of these is nucleoplasmin-like protein (NLP), which we had previously shown to play a role in ES control. In addition, we identify two novel ISWI partners, regulator of chromosome condensation 1-like protein (RCCP) and phenylalanine/tyrosine-rich protein (FYRP), both containing protein motifs typically found on chromatin proteins. Knockdown of RCCP or FYRP in bloodstream form T. brucei results in derepression of silent variant surface glycoprotein ESs, as had previously been shown for TbISWI and NLP. All four proteins are expressed and interact with each other in both major life cycle stages and show similar distributions at Pol I-transcribed loci. They are also found at Pol II strand switch regions as determined with ChIP. ISWI, NLP, RCCP, and FYRP therefore appear to form a single major ISWI complex in T. brucei (TbIC). This reduced complexity of ISWI regulation and the presence of novel ISWI partners highlights the early divergence of trypanosomes in evolution. PMID- 26378229 TI - Amino Acid Availability Modulates Vacuolar H+-ATPase Assembly. AB - The vacuolar H(+)-ATPase (V-ATPase) is an ATP-dependent proton pump composed of a peripheral ATPase domain (V1) and a membrane-integral proton-translocating domain (V0) and is involved in many normal and disease processes. An important mechanism of regulating V-ATPase activity is reversible assembly of the V1 and V0 domains. Increased assembly in mammalian cells occurs under various conditions and has been shown to involve PI3K. The V-ATPase is necessary for amino acid-induced activation of mechanistic target of rapamycin complex 1 (mTORC1), which is important in controlling cell growth in response to nutrient availability and growth signals. The V-ATPase undergoes amino acid-dependent interactions with the Ragulator complex, which is involved in recruitment of mTORC1 to the lysosomal membrane during amino acid sensing. We hypothesized that changes in the V ATPase/Ragulator interaction might involve amino acid-dependent changes in V ATPase assembly. To test this, we measured V-ATPase assembly by cell fractionation in HEK293T cells treated with and without amino acids. V-ATPase assembly increases upon amino acid starvation, and this effect is reversed upon readdition of amino acids. Lysosomes from amino acid-starved cells possess greater V-ATPase-dependent proton transport, indicating that assembled pumps are catalytically active. Amino acid-dependent changes in both V-ATPase assembly and activity are independent of PI3K and mTORC1 activity, indicating the involvement of signaling pathways distinct from those implicated previously in controlling assembly. By contrast, lysosomal neutralization blocks the amino acid-dependent change in assembly and reactivation of mTORC1 after amino acid starvation. These results identify an important new stimulus for controlling V-ATPase assembly. PMID- 26378230 TI - A trans-Regulatory Code for the Forebrain Expression of Six3.2 in the Medaka Fish. AB - A well integrated and hierarchically organized gene regulatory network is responsible for the progressive specification of the forebrain. The transcription factor Six3 is one of the central components of this network. As such, Six3 regulates several components of the network, but its upstream regulators are still poorly characterized. Here we have systematically identified such regulators, taking advantage of the detailed functional characterization of the regulatory region of the medaka fish Six3.2 ortholog and of a time/cost-effective trans-regulatory screening, which complemented and overcame the limitations of in silico prediction approaches. The candidates resulting from this search were validated with dose-response luciferase assays and expression pattern criteria. Reconfirmed candidates with a matching expression pattern were also tested with chromatin immunoprecipitation and functional studies. Our results confirm the previously proposed direct regulation of Pax6 and further demonstrate that Msx2 and Pbx1 are bona fide direct regulators of early Six3.2 distribution in distinct domains of the medaka fish forebrain. They also point to other transcription factors, including Tcf3, as additional regulators of different spatial-temporal domains of Six3.2 expression. The activity of these regulators is discussed in the context of the gene regulatory network proposed for the specification of the forebrain. PMID- 26378231 TI - Directed evolution of the Escherichia coli cAMP receptor protein at the cAMP pocket. AB - The Escherichia coli cAMP receptor protein (CRP) requires cAMP binding to undergo a conformational change for DNA binding and transcriptional regulation. Two CRP residues, Thr(127) and Ser(128), are known to play important roles in cAMP binding through hydrogen bonding and in the cAMP-induced conformational change, but the connection between the two is not completely clear. Here, we simultaneously randomized the codons for these two residues and selected CRP mutants displaying high CRP activity in a cAMP-producing E. coli. Many different CRP mutants satisfied the screening condition for high CRP activity, including those that cannot form any hydrogen bonds with the incoming cAMP at the two positions. In vitro DNA-binding analysis confirmed that these selected CRP mutants indeed display high CRP activity in response to cAMP. These results indicate that the hydrogen bonding ability of the Thr(127) and Ser(128) residues is not critical for the cAMP-induced CRP activation. However, the hydrogen bonding ability of Thr(127) and Ser(128) was found to be important in attaining high cAMP affinity. Computational analysis revealed that most natural cAMP sensing CRP homologs have Thr/Ser, Thr/Thr, or Thr/Asn at positions 127 and 128. All of these pairs are excellent hydrogen bonding partners and they do not elevate CRP activity in the absence of cAMP. Taken together, our analyses suggest that CRP evolved to have hydrogen bonding residues at the cAMP pocket residues 127 and 128 for performing dual functions: preserving high cAMP affinity and keeping CRP inactive in the absence of cAMP. PMID- 26378233 TI - Formation of a Ternary Complex for Selenocysteine Biosynthesis in Bacteria. AB - The synthesis of selenocysteine-containing proteins (selenoproteins) involves the interaction of selenocysteine synthase (SelA), tRNA (tRNA(Sec)), selenophosphate synthetase (SelD, SPS), a specific elongation factor (SelB), and a specific mRNA sequence known as selenocysteine insertion sequence (SECIS). Because selenium compounds are highly toxic in the cellular environment, the association of selenium with proteins throughout its metabolism is essential for cell survival. In this study, we demonstrate the interaction of SPS with the SelA-tRNA(Sec) complex, resulting in a 1.3-MDa ternary complex of 27.0 +/- 0.5 nm in diameter and 4.02 +/- 0.05 nm in height. To assemble the ternary complex, SPS undergoes a conformational change. We demonstrated that the glycine-rich N-terminal region of SPS is crucial for the SelA-tRNA(Sec)-SPS interaction and selenoprotein biosynthesis, as revealed by functional complementation experiments. Taken together, our results provide new insights into selenoprotein biosynthesis, demonstrating for the first time the formation of the functional ternary SelA tRNA(Sec)-SPS complex. We propose that this complex is necessary for proper selenocysteine synthesis and may be involved in avoiding the cellular toxicity of selenium compounds. PMID- 26378232 TI - Identification of Middle Chain Fatty Acyl-CoA Ligase Responsible for the Biosynthesis of 2-Alkylmalonyl-CoAs for Polyketide Extender Unit. AB - Understanding the biosynthetic mechanism of the atypical polyketide extender unit is important for the development of bioactive natural products. Reveromycin (RM) derivatives produced by Streptomyces sp. SN-593 possess several aliphatic extender units. Here, we studied the molecular basis of 2-alkylmalonyl-CoA formation by analyzing the revR and revS genes, which form a transcriptional unit with the revT gene, a crotonyl-CoA carboxylase/reductase homolog. We mainly focused on the uncharacterized adenylate-forming enzyme (RevS). revS gene disruption resulted in the reduction of all RM derivatives, whereas reintroduction of the gene restored the yield of RMs. Although RevS was classified in the fatty acyl-AMP ligase clade based on phylogenetic analysis, biochemical characterization revealed that the enzyme catalyzed the middle chain fatty acyl-CoA ligase (FACL) but not the fatty acyl-AMP ligase activity, suggesting the molecular evolution for acyl-CoA biosynthesis. Moreover, we examined the in vitro conversion of fatty acid into 2-alkylmalonyl-CoA using purified RevS and RevT. The coupling reaction showed efficient conversion of hexenoic acid into butylmalonyl-CoA. RevS efficiently catalyzed C8-C10 middle chain FACL activity; therefore, we speculated that the acyl-CoA precursor was truncated via beta-oxidation and converted into (E)-2-enoyl-CoA, a RevT substrate. To determine whether the beta-oxidation process is involved between the RevS and RevT reaction, we performed the feeding experiment using [1,2,3,4 (13)C]octanoic acid. (13)C NMR analysis clearly demonstrated incorporation of the [3,4-(13)C]octanoic acid moiety into the structure of RM-A. Our results provide insight into the role of uncharacterized RevS homologs that may catalyze middle chain FACL to produce a unique polyketide extender unit. PMID- 26378234 TI - Aberrant Retinoblastoma (RB)-E2F Transcriptional Regulation Defines Molecular Phenotypes of Osteosarcoma. AB - We previously identified two distinct molecular subtypes of osteosarcoma through gene expression profiling. These subtypes are associated with distinct tumor behavior and clinical outcomes. Here, we describe mechanisms that give rise to these molecular subtypes. Using bioinformatic analyses, we identified a significant association between deregulation of the retinoblastoma (RB)-E2F pathway and the molecular subtype with worse clinical outcomes. Xenotransplantation models recapitulated the corresponding behavior for each osteosarcoma subtype; thus, we used cell lines to validate the role of the RB-E2F pathway in regulating the prognostic gene signature. Ectopic RB resets the patterns of E2F regulated gene expression in cells derived from tumors with worse clinical outcomes (molecular phenotype 2) to those comparable with those observed in cells derived from tumors with less aggressive outcomes (molecular phenotype 1), providing a functional association between RB-E2F dysfunction and altered gene expression in osteosarcoma. DNA methyltransferase and histone deacetylase inhibitors similarly reset the transcriptional state of the molecular phenotype 2 cells from a state associated with RB deficiency to one seen with RB sufficiency. Our data indicate that deregulation of RB-E2F pathway alters the epigenetic landscape and biological behavior of osteosarcoma. PMID- 26378235 TI - The Responses of Hyperglycemic Dividing Mesangial Cells to Heparin Are Mediated by the Non-reducing Terminal Trisaccharide. AB - Our previous studies showed: (i) that growth-arrested G0/G1 rat mesangial cells stimulated to divide in hyperglycemic medium initiate intracellular hyaluronan synthesis that induces autophagy and the cyclin D3-induced formation of a monocyte-adhesive extracellular hyaluronan matrix after completing cell division; and (ii) that heparin inhibits the intracellular hyaluronan and autophagy responses, but after completing division, induces hyaluronan synthesis at the plasma membrane with the formation of a larger monocyte-adhesive hyaluronan matrix. This study shows: (i) that the non-terminal trisaccharide of heparin is sufficient to initiate the same responses as intact heparin, (ii) that a fully sulfated tetrasaccharide isolated from bacterial heparin lyase 1 digests of heparin that contains a Delta-2S-iduronate on the non-reducing end does not initiate the same responses as intact heparin, and (iii) that removal of the Delta-2S-iduronate to expose the fully sulfated trisaccharide (GlcNS(6S) IdoUA(2S)-GlcNS(6S)) does initiate the same responses as intact heparin. These results provide evidence that mammalian heparanase digestion of heparin and heparan sulfate exposes a cryptic motif on the non-reducing termini that is recognized by a receptor on dividing cells. PMID- 26378236 TI - FACT Proteins, SUPT16H and SSRP1, Are Transcriptional Suppressors of HIV-1 and HTLV-1 That Facilitate Viral Latency. AB - Our functional genomic RNAi screens have identified the protein components of the FACT (facilitates chromatin transcription) complex, SUPT16H and SSRP1, as top host factors that negatively regulate HIV-1 replication. FACT interacts specifically with histones H2A/H2B to affect assembly and disassembly of nucleosomes, as well as transcription elongation. We further investigated the suppressive role of FACT proteins in HIV-1 transcription. First, depletion of SUPT16H or SSRP1 protein enhances Tat-mediated HIV-1 LTR (long terminal repeat) promoter activity. Second, HIV-1 Tat interacts with SUPT16H but not SSRP1 protein. However, both SUPT16H and SSRP1 are recruited to LTR promoter. Third, the presence of SUPT16H interferes with the association of Cyclin T1 (CCNT1), a subunit of P-TEFb, with the Tat-LTR axis. Removing inhibitory mechanisms to permit HIV-1 transcription is an initial and key regulatory step to reverse post integrated latent HIV-1 proviruses for purging of reservoir cells. We therefore evaluated the role of FACT proteins in HIV-1 latency and reactivation. Depletion of SUPT16H or SSRP1 protein affects both HIV-1 transcriptional initiation and elongation and spontaneously reverses latent HIV-1 in U1/HIV and J-LAT cells. Similar effects were observed with a primary CD4+ T cell model of HIV-1 latency. FACT proteins also interfere with HTLV-1 Tax-LTR-mediated transcription and viral latency, indicating that they may act as general transcriptional suppressors for retroviruses. We conclude that FACT proteins SUPT16H and SSRP1 play a key role in suppressing HIV-1 transcription and promoting viral latency, which may serve as promising gene targets for developing novel HIV-1 latency-reversing agents. PMID- 26378237 TI - Epoxyqueuosine Reductase Structure Suggests a Mechanism for Cobalamin-dependent tRNA Modification. AB - Queuosine (Q) is a hypermodified RNA base that replaces guanine in the wobble positions of 5'-GUN-3' tRNA molecules. Q is exclusively made by bacteria, and the corresponding queuine base is a micronutrient salvaged by eukaryotic species. The final step in Q biosynthesis is the reduction of the epoxide precursor, epoxyqueuosine, to yield the Q cyclopentene ring. The epoxyqueuosine reductase responsible, QueG, shares distant homology with the cobalamin-dependent reductive dehalogenase (RdhA), however the role played by cobalamin in QueG catalysis has remained elusive. We report the solution and structural characterization of Streptococcus thermophilus QueG, revealing the enzyme harbors a redox chain consisting of two [4Fe-4S] clusters and a cob(II)alamin in the base-off form, similar to RdhAs. In contrast to the shared redox chain architecture, the QueG active site shares little homology with RdhA, with the notable exception of a conserved Tyr that is proposed to function as a proton donor during reductive dehalogenation. Docking of an epoxyqueuosine substrate suggests the QueG active site places the substrate cyclopentane moiety in close proximity of the cobalt. Both the Tyr and a conserved Asp are implicated as proton donors to the epoxide leaving group. This suggests that, in contrast to the unusual carbon-halogen bond chemistry catalyzed by RdhAs, QueG acts via Co-C bond formation. Our study establishes the common features of Class III cobalamin-dependent enzymes, and reveals an unexpected diversity in the reductive chemistry catalyzed by these enzymes. PMID- 26378238 TI - Structural Basis of Neuronal Nitric-oxide Synthase Interaction with Dystrophin Repeats 16 and 17. AB - Duchenne muscular dystrophy is a lethal genetic defect that is associated with the absence of dystrophin protein. Lack of dystrophin protein completely abolishes muscular nitric-oxide synthase (NOS) function as a regulator of blood flow during muscle contraction. In normal muscles, nNOS function is ensured by its localization at the sarcolemma through an interaction of its PDZ domain with dystrophin spectrin-like repeats R16 and R17. Early studies suggested that repeat R17 is the primary site of interaction but ignored the involved nNOS residues, and the R17 binding site has not been described at an atomic level. In this study, we characterized the specific amino acids involved in the binding site of nNOS-PDZ with dystrophin R16-17 using combined experimental biochemical and structural in silico approaches. First, 32 alanine-scanning mutagenesis variants of dystrophin R16-17 indicated the regions where mutagenesis modified the affinity of the dystrophin interaction with the nNOS-PDZ. Second, using small angle x-ray scattering-based models of dystrophin R16-17 and molecular docking methods, we generated atomic models of the dystrophin R16-17.nNOS-PDZ complex that correlated well with the alanine scanning identified regions of dystrophin. The structural regions constituting the dystrophin interaction surface involve the A/B loop and the N-terminal end of helix B of repeat R16 and the N-terminal end of helix A' and a small fraction of helix B' and a large part of the helix C' of repeat R17. The interaction surface of nNOS-PDZ involves its main beta-sheet and its specific C-terminal beta-finger. PMID- 26378239 TI - Mitotic Protein CSPP1 Interacts with CENP-H Protein to Coordinate Accurate Chromosome Oscillation in Mitosis. AB - Mitotic chromosome segregation is orchestrated by the dynamic interaction of spindle microtubules with the kinetochores. During chromosome alignment, kinetochore-bound microtubules undergo dynamic cycles between growth and shrinkage, leading to an oscillatory movement of chromosomes along the spindle axis. Although kinetochore protein CENP-H serves as a molecular control of kinetochore-microtubule dynamics, the mechanistic link between CENP-H and kinetochore microtubules (kMT) has remained less characterized. Here, we show that CSPP1 is a kinetochore protein essential for accurate chromosome movements in mitosis. CSPP1 binds to CENP-H in vitro and in vivo. Suppression of CSPP1 perturbs proper mitotic progression and compromises the satisfaction of spindle assembly checkpoint. In addition, chromosome oscillation is greatly attenuated in CSPP1-depleted cells, similar to what was observed in the CENP-H-depleted cells. Importantly, CSPP1 depletion enhances velocity of kinetochore movement, and overexpression of CSPP1 decreases the speed, suggesting that CSPP1 promotes kMT stability during cell division. Specific perturbation of CENP-H/CSPP1 interaction using a membrane-permeable competing peptide resulted in a transient mitotic arrest and chromosome segregation defect. Based on these findings, we propose that CSPP1 cooperates with CENP-H on kinetochores to serve as a novel regulator of kMT dynamics for accurate chromosome segregation. PMID- 26378240 TI - Engineering a monolignol 4-O-methyltransferase with high selectivity for the condensed lignin precursor coniferyl alcohol. AB - Lignin, a rigid biopolymer in plant cell walls, is derived from the oxidative polymerization of three monolignols. The composition of monolignol monomers dictates the degree of lignin condensation, reactivity, and thus the degradability of plant cell walls. Guaiacyl lignin is regarded as the condensed structural unit. Polymerization of lignin is initiated through the deprotonation of the para-hydroxyl group of monolignols. Therefore, preferentially modifying the para-hydroxyl of a specific monolignol to deprive its dehydrogenation propensity would disturb the formation of particular lignin subunits. Here, we test the hypothesis that specific remodeling the active site of a monolignol 4-O methyltransferase would create an enzyme that specifically methylates the condensed guaiacyl lignin precursor coniferyl alcohol. Combining crystal structural information with combinatorial active site saturation mutagenesis and starting with the engineered promiscuous enzyme, MOMT5 (T133L/E165I/F175I/F166W/H169F), we incrementally remodeled its substrate binding pocket by the addition of four substitutions, i.e. M26H, S30R, V33S, and T319M, yielding a mutant enzyme capable of discriminately etherifying the para-hydroxyl of coniferyl alcohol even in the presence of excess sinapyl alcohol. The engineered enzyme variant has a substantially reduced substrate binding pocket that imposes a clear steric hindrance thereby excluding bulkier lignin precursors. The resulting enzyme variant represents an excellent candidate for modulating lignin composition and/or structure in planta. PMID- 26378241 TI - ATG4B (Autophagin-1) phosphorylation modulates autophagy. AB - Autophagy is a catabolic cellular mechanism for entrapping cellular macromolecules and organelles in intracellular vesicles and degrading their contents by fusion with lysosomes. Important roles for autophagy have been elucidated for cell survival during nutrient insufficiency, eradication of intracellular pathogens, and counteracting aging through clearance of senescent proteins and mitochondria. Autophagic vesicles become decorated with LC3, a protein that mediates their fusion with lysosomes. LC3 is a substrate of the cysteine protease ATG4B (Autophagin-1), where cleavage generates a C-terminal glycine required for LC3 conjugation to lipids in autophagosomes. ATG4B both cleaves pro-LC3 and also hydrolyzes lipids from cleaved LC3. We show here that phosphorylation of ATG4B at Ser-383 and Ser-392 increases its hydrolyase activity as measured using LC3 as a substrate. Reconstituting atg4b(-/-) cells with phosphorylation-deficient ATG4B showed a role of ATG4B phosphorylation in LC3 delipidation and autophagic flux, thus demonstrating that the cellular activity of ATG4B is modulated by phosphorylation. Proteolytic conversion of pro-LC3 to LC3-I was not significantly impacted by ATG4B phosphorylation in cells. Phosphorylation-deficient ATG4B also showed reduced interactions with the lipid conjugated LC3 but not unconjugated LC3. Taken together, these findings demonstrate a role for Ser-383 and Ser-392 phosphorylation of ATG4B in control of autophagy. PMID- 26378242 TI - Parkinson's disease: From human genetics to clinical trials. AB - Combining genetic insights into the pathogenesis of Parkinson's disease (PD) with findings from animal and cellular models of this disorder has advanced our understanding of the pathways that lead to the characteristic degeneration of dopaminergic neurons in the brain's nigrostriatal pathway. This has fueled an increase in candidate compounds designed to modulate these pathways and to alter the processes underlying neuronal death in this disorder. Using mitochondrial quality control and the macroautophagy/lysosomal pathways as examples, we discuss the pipeline from a comprehensive genetic architecture for PD through to clinical trials for drugs targeting pathways linked to neurodegeneration in PD. We also identify opportunities and pitfalls on the road to a clinically effective disease modifying treatment for this disease. PMID- 26378243 TI - Targeting the glucocorticoid receptor in breast and prostate cancers. AB - Steroid receptors for androgens and estrogens have essential roles in prostate and breast cancers. Recently, glucocorticoid receptor (GR) activity has also been proposed as having an important role in these cancers. Underscoring the cooperative nature of nuclear receptor activity, data now suggest that GR function in prostate and breast cancers is dependent on the tumor's concomitant androgen or estrogen receptor activity. PMID- 26378244 TI - Durable sequence stability and bone marrow tropism in a macaque model of human pegivirus infection. AB - Human pegivirus (HPgV)-formerly known as GB virus C and hepatitis G virus-is a poorly characterized RNA virus that infects about one-sixth of the global human population and is transmitted frequently in the blood supply. We create an animal model of HPgV infection by infecting macaque monkeys with a new simian pegivirus (SPgV) discovered in wild baboons. Using this model, we provide a high resolution, longitudinal picture of SPgV viremia where the dose, route, and timing of infection are known. We detail the highly variable acute phase of SPgV infection, showing that the viral load trajectory early in infection is dependent on the infecting dose, whereas the chronic-phase viremic set point is not. We also show that SPgV has an extremely low propensity for accumulating sequence variation, with no consensus-level variants detected during the acute phase of infection and an average of only 1.5 variants generated per 100 infection-days. Finally, we show that SPgV RNA is highly concentrated in only two tissues: spleen and bone marrow, with bone marrow likely producing most of the virus detected in plasma. Together, these results reconcile several paradoxical observations from cross-sectional analyses of HPgV in humans and provide an animal model for studying pegivirus biology. PMID- 26378245 TI - CT-guided injection of a TRPV1 agonist around dorsal root ganglia decreases pain transmission in swine. AB - One approach to analgesia is to block pain at the site of origin or along the peripheral pathway by selectively ablating pain-transmitting neurons or nerve terminals directly. The heat/capsaicin receptor (TRPV1) expressed by nociceptive neurons is a compelling target for selective interventional analgesia because it leaves somatosensory and proprioceptive neurons intact. Resiniferatoxin (RTX), like capsaicin, is a TRPV1 agonist but has greater potency. We combine RTX mediated inactivation with the precision of computed tomography (CT)-guided delivery to ablate peripheral pain fibers in swine. Under CT guidance, RTX was delivered unilaterally around the lumbar dorsal root ganglia (DRG), and vehicle only was administered to the contralateral side. During a 4-week observation period, animals demonstrated delayed or absent withdrawal responses to infrared laser heat stimuli delivered to sensory dermatomes corresponding to DRG receiving RTX treatment. Motor function was unimpaired as assessed by disability scoring and gait analysis. In treated DRG, TRPV1 mRNA expression was reduced, as were nociceptive neuronal perikarya in ganglia and their nerve terminals in the ipsilateral dorsal horn. CT guidance to precisely deliver RTX to sites of peripheral pain transmission in swine may be an approach that could be tailored to block an array of clinical pain conditions in patients. PMID- 26378246 TI - Effects of caffeine on the human circadian clock in vivo and in vitro. AB - Caffeine's wakefulness-promoting and sleep-disrupting effects are well established, yet whether caffeine affects human circadian timing is unknown. We show that evening caffeine consumption delays the human circadian melatonin rhythm in vivo and that chronic application of caffeine lengthens the circadian period of molecular oscillations in vitro, primarily with an adenosine receptor/cyclic adenosine monophosphate (AMP)-dependent mechanism. In a double blind, placebo-controlled, ~49-day long, within-subject study, we found that consumption of a caffeine dose equivalent to that in a double espresso 3 hours before habitual bedtime induced a ~40-min phase delay of the circadian melatonin rhythm in humans. This magnitude of delay was nearly half of the magnitude of the phase-delaying response induced by exposure to 3 hours of evening bright light (~3000 lux, ~7 W/m(2)) that began at habitual bedtime. Furthermore, using human osteosarcoma U2OS cells expressing clock gene luciferase reporters, we found a dose-dependent lengthening of the circadian period by caffeine. By pharmacological dissection and small interfering RNA knockdown, we established that perturbation of adenosine receptor signaling, but not ryanodine receptor or phosphodiesterase activity, was sufficient to account for caffeine's effects on cellular timekeeping. We also used a cyclic AMP biosensor to show that caffeine increased cyclic AMP levels, indicating that caffeine influenced a core component of the cellular circadian clock. Together, our findings demonstrate that caffeine influences human circadian timing, showing one way that the world's most widely consumed psychoactive drug affects human physiology. PMID- 26378247 TI - Sparing the region of the salivary gland containing stem cells preserves saliva production after radiotherapy for head and neck cancer. AB - Each year, 500,000 patients are treated with radiotherapy for head and neck cancer, resulting in relatively high survival rates. However, in 40% of patients, quality of life is severely compromised because of radiation-induced impairment of salivary gland function and consequent xerostomia (dry mouth). New radiation treatment technologies enable sparing of parts of the salivary glands. We have determined the parts of the major salivary gland, the parotid gland, that need to be spared to ensure that the gland continues to produce saliva after irradiation treatment. In mice, rats, and humans, we showed that stem and progenitor cells reside in the region of the parotid gland containing the major ducts. We demonstrated in rats that inclusion of the ducts in the radiation field led to loss of regenerative capacity, resulting in long-term gland dysfunction with reduced saliva production. Then we showed in a cohort of patients with head and neck cancer that the radiation dose to the region of the salivary gland containing the stem/progenitor cells predicted the function of the salivary glands one year after radiotherapy. Finally, we showed that this region of the salivary gland could be spared during radiotherapy, thus reducing the risk of post-radiotherapy xerostomia. PMID- 26378248 TI - Intracellular accumulation of indium ions released from nanoparticles induces oxidative stress, proinflammatory response and DNA damage. AB - Due to the widespread use of indium tin oxide (ITO), it is important to investigate its effect on human health. In this study, we evaluated the cellular effects of ITO nanoparticles (NPs), indium chloride (InCl3) and tin chloride (SnCl3) using human lung epithelial A549 cells. Transmission electron microscopy and inductively coupled plasma mass spectrometry were employed to study cellular ITO NP uptake. Interestingly, greater uptake of ITO NPs was observed, as compared with soluble salts. ITO NP species released could be divided into two types: 'indium release ITO' or 'tin release ITO'. We incubated A549 cells with indium release ITO, tin release ITO, InCl3 or SnCl2 and investigated oxidative stress, proinflammatory response, cytotoxicity and DNA damage. We found that intracellular reactive oxygen species were increased in cells incubated with indium release ITO, but not tin release ITO, InCl3 or SnCl2. Messenger RNA and protein levels of the inflammatory marker, interleukin-8, also increased following exposure to indium release ITO. Furthermore, the alkaline comet assay revealed that intracellular accumulation of indium ions induced DNA damage. Our results demonstrate that the accumulation of ionic indium, but not ionic tin, from ITO NPs in the intracellular matrix has extensive cellular effects. PMID- 26378249 TI - Sensitive, nonradioactive assay of phosphorylase kinase through measurement of enhanced phosphorylase activity towards fluorogenic dextrin. AB - Glycogen phosphorylase (GP) exists in two interconvertible forms, GPa (phosphorylated form, high activity) and GPb (nonphosphorylated form, low activity). Phosphorylase kinase (PhK) catalyses the phosphorylation of GPb and plays a key role in the cascade system for regulating glycogen metabolism. In this study, we developed a highly sensitive and nonradioactive assay for PhK activity by measuring the enhanced GP activity towards a pyridylaminated maltohexaose. The enhanced GP activity (DeltaA) was calculated by the following formula: DeltaA = A(+) - A(0), where A(+) and A(0) represent the GP activities of the PhK-treated and PhK-nontreated samples, respectively. Using a high performance liquid chromatograph equipped with a fluorescence spectrophotometer, the product of GP activity could be isolated and quantified at 10 fmol. This method does not require the use of any radioactive compounds and only 1 ug of GPb per sample was needed to obtain A(+) and A(0) values. The remarkable reduction in GPb concentration enabled us to discuss an interesting new role for glycogen in PhK activity. PMID- 26378250 TI - Interallelic complementation provides functional evidence for cohesin-cohesin interactions on DNA. AB - The cohesin complex (Mcd1p, Smc1p, Smc3p, and Scc3p) has multiple roles in chromosome architecture, such as promoting sister chromatid cohesion, chromosome condensation, DNA repair, and transcriptional regulation. The prevailing embrace model for sister chromatid cohesion posits that a single cohesin complex entraps both sister chromatids. We report interallelic complementation between pairs of nonfunctional mcd1 alleles (mcd1-1 and mcd1-Q266) or smc3 alleles (smc3-42 and smc3-K113R). Cells bearing individual mcd1 or smc3 mutant alleles are inviable and defective for both sister chromatid cohesion and condensation. However, cells coexpressing two defective mcd1 or two defective smc3 alleles are viable and have cohesion and condensation. Because cohesin contains only a single copy of Smc3p or Mcd1p, these examples of interallelic complementation must result from interplay or communication between the two defective cohesin complexes, each harboring one of the mutant allele products. Neither mcd1-1p nor smc3-42p is bound to chromosomes when expressed individually at its restrictive temperature. However, their chromosome binding is restored when they are coexpressed with their chromosome-bound interallelic complementing partner. Our results support a mechanism by which multiple cohesin complexes interact on DNA to mediate cohesion and condensation. PMID- 26378251 TI - Activation of G proteins by GIV-GEF is a pivot point for insulin resistance and sensitivity. AB - Insulin resistance (IR) is a metabolic disorder characterized by impaired insulin signaling and cellular glucose uptake. The current paradigm for insulin signaling centers upon the insulin receptor (InsR) and its substrate IRS1; the latter is believed to be the sole conduit for postreceptor signaling. Here we challenge that paradigm and show that GIV/Girdin, a guanidine exchange factor (GEF) for the trimeric G protein Galphai, is another major hierarchical conduit for the metabolic insulin response. By virtue of its ability to directly bind InsR, IRS1, and phosphoinositide 3-kinase, GIV serves as a key hub in the immediate postreceptor level, which coordinately enhances the metabolic insulin response and glucose uptake in myotubes via its GEF function. Site-directed mutagenesis or phosphoinhibition of GIV-GEF by the fatty acid/protein kinase C-theta pathway triggers IR. Insulin sensitizers reverse phosphoinhibition of GIV and reinstate insulin sensitivity. We also provide evidence for such reversible regulation of GIV-GEF in skeletal muscles from patients with IR. Thus GIV is an essential upstream component that couples InsR to G-protein signaling to enhance the metabolic insulin response, and impairment of such coupling triggers IR. We also provide evidence that GIV-GEF serves as therapeutic target for exogenous manipulation of physiological insulin response and reversal of IR in skeletal muscles. PMID- 26378252 TI - ARF-GEF cytohesin-2/ARNO regulates R-Ras and alpha5-integrin recycling through an EHD1-positive compartment. AB - When expressed in epithelial cells, cytohesin-2/ARNO, a guanine nucleotide exchange factor (GEF) for ARF small GTPases, causes a robust migration response. Recent evidence suggests that cytohesin-2/ARNO acts downstream of small the GTPase R-Ras to promote spreading and migration. We hypothesized that cytohesin 2/ARNO could transmit R-Ras signals by regulating the recycling of R-Ras through ARF activation. We found that Eps15-homology domain 1 (EHD1), a protein that associates with the endocytic recycling compartment (ERC), colocalizes with active R-Ras in transiently expressed HeLa cells. In addition, we show that EHD1 positive recycling endosomes are a novel compartment for cytohesin-2/ARNO. Knockdown or expression of GEF-inactive (E156K) cytohesin-2/ARNO causes R-Ras to accumulate on recycling endosomes containing EHD1 and inhibits cell spreading. E156K-ARNO also causes a reduction in focal adhesion size and number. Finally, we demonstrate that R-Ras/ARNO signaling is required for recycling of alpha5 integrin and R-Ras to the plasma membrane. These data establish a role for cytohesin-2/ARNO as a regulator of R-Ras and integrin recycling and suggest that ARF-regulated trafficking of R-Ras is required for R-Ras-dependent effects on spreading and adhesion formation. PMID- 26378253 TI - Orchestration of ErbB3 signaling through heterointeractions and homointeractions. AB - Members of the ErbB family of receptor tyrosine kinases are capable of both homointeractions and heterointeractions. Because each receptor has a unique set of binding sites for downstream signaling partners and differential catalytic activity, subtle shifts in their combinatorial interplay may have a large effect on signaling outcomes. The overexpression and mutation of ErbB family members are common in numerous human cancers and shift the balance of activation within the signaling network. Here we report the development of a spatial stochastic model that addresses the dynamics of ErbB3 homodimerization and heterodimerization with ErbB2. The model is based on experimental measures for diffusion, dimer off rates, kinase activity, and dephosphorylation. We also report computational analysis of ErbB3 mutations, generating the prediction that activating mutations in the intracellular and extracellular domains may be subdivided into classes with distinct underlying mechanisms. We show experimental evidence for an ErbB3 gain-of-function point mutation located in the C-lobe asymmetric dimerization interface, which shows enhanced phosphorylation at low ligand dose associated with increased kinase activity. PMID- 26378254 TI - Conserved function of the lysine-based KXD/E motif in Golgi retention for endomembrane proteins among different organisms. AB - We recently identified a new COPI-interacting KXD/E motif in the C-terminal cytosolic tail (CT) of Arabidopsis endomembrane protein 12 (AtEMP12) as being a crucial Golgi retention mechanism for AtEMP12. This KXD/E motif is conserved in CTs of all EMPs found in plants, yeast, and humans and is also present in hundreds of other membrane proteins. Here, by cloning selective EMP isoforms from plants, yeast, and mammals, we study the localizations of EMPs in different expression systems, since there are contradictory reports on the localizations of EMPs. We show that the N-terminal and C-terminal GFP-tagged EMP fusions are localized to Golgi and post-Golgi compartments, respectively, in plant, yeast, and mammalian cells. In vitro pull-down assay further proves the interaction of the KXD/E motif with COPI coatomer in yeast. COPI loss of function in yeast and plants causes mislocalization of EMPs or KXD/E motif-containing proteins to vacuole. Ultrastructural studies further show that RNA interference (RNAi) knockdown of coatomer expression in transgenic Arabidopsis plants causes severe morphological changes in the Golgi. Taken together, our results demonstrate that N-terminal GFP fusions reflect the real localization of EMPs, and KXD/E is a conserved motif in COPI interaction and Golgi retention in eukaryotes. PMID- 26378255 TI - Discovery of a vezatin-like protein for dynein-mediated early endosome transport. AB - Early endosomes are transported bidirectionally by cytoplasmic dynein and kinesin 3, but how the movements are regulated in vivo remains unclear. Here our forward genetic study led to the discovery of VezA, a vezatin-like protein in Aspergillus nidulans, as a factor critical for early endosome distribution. Loss of vezA causes an abnormal accumulation of early endosomes at the hyphal tip, where microtubule plus ends are located. This abnormal accumulation depends on kinesin 3 and is due to a decrease in the frequency but not the speed of dynein-mediated early endosome movement. VezA-GFP signals are enriched at the hypha tip in an actin-dependent manner but are not obviously associated with early endosomes, thus differing from the early endosome association of the cargo adapter HookA (Hook in A. nidulans). On loss of VezA, HookA associates normally with early endosomes, but the interaction between dynein-dynactin and the early-endosome bound HookA is significantly decreased. However, VezA is not required for linking dynein-dynactin to the cytosolic ?C-HookA, lacking the cargo-binding C-terminus. These results identify VezA as a novel regulator required for the interaction between dynein and the Hook-bound early endosomes in vivo. PMID- 26378256 TI - Crescerin uses a TOG domain array to regulate microtubules in the primary cilium. AB - Eukaryotic cilia are cell-surface projections critical for sensing the extracellular environment. Defects in cilia structure and function result in a broad range of developmental and sensory disorders. However, mechanisms that regulate the microtubule (MT)-based scaffold forming the cilia core are poorly understood. TOG domain array-containing proteins ch-TOG and CLASP are key regulators of cytoplasmic MTs. Whether TOG array proteins also regulate ciliary MTs is unknown. Here we identify the conserved Crescerin protein family as a cilia-specific, TOG array-containing MT regulator. We present the crystal structure of mammalian Crescerin1 TOG2, revealing a canonical TOG fold with conserved tubulin-binding determinants. Crescerin1's TOG domains possess inherent MT-binding activity and promote MT polymerization in vitro. Using Cas9-triggered homologous recombination in Caenorhabditis elegans, we demonstrate that the worm Crescerin family member CHE-12 requires TOG domain-dependent tubulin-binding activity for sensory cilia development. Thus, Crescerin expands the TOG domain array-based MT regulatory paradigm beyond ch-TOG and CLASP, representing a distinct regulator of cilia structure. PMID- 26378257 TI - Caenorhabditis elegans Aurora A kinase is required for the formation of spindle microtubules in female meiosis. AB - In many animals, female meiotic spindles are assembled in the absence of centrosomes, the major microtubule (MT)-organizing centers. How MTs are formed and organized into meiotic spindles is poorly understood. Here we report that, in Caenorhabditis elegans, Aurora A kinase/AIR-1 is required for the formation of spindle microtubules during female meiosis. When AIR-1 was depleted or its kinase activity was inhibited in C. elegans oocytes, although MTs were formed around chromosomes at germinal vesicle breakdown (GVBD), they were decreased during meiotic prometaphase and failed to form a bipolar spindle, and chromosomes were not separated into two masses. Whereas AIR-1 protein was detected on and around meiotic spindles, its kinase-active form was concentrated on chromosomes at prometaphase and on interchromosomal MTs during late anaphase and telophase. We also found that AIR-1 is involved in the assembly of short, dynamic MTs in the meiotic cytoplasm, and these short MTs were actively incorporated into meiotic spindles. Collectively our results suggest that, after GVBD, the kinase activity of AIR-1 is continuously required for the assembly and/or stabilization of female meiotic spindle MTs. PMID- 26378258 TI - Diffusion of GPI-anchored proteins is influenced by the activity of dynamic cortical actin. AB - Molecular diffusion at the surface of living cells is believed to be predominantly driven by thermal kicks. However, there is growing evidence that certain cell surface molecules are driven by the fluctuating dynamics of cortical cytoskeleton. Using fluorescence correlation spectroscopy, we measure the diffusion coefficient of a variety of cell surface molecules over a temperature range of 24-37 degrees C. Exogenously incorporated fluorescent lipids with short acyl chains exhibit the expected increase of diffusion coefficient over this temperature range. In contrast, we find that GPI-anchored proteins exhibit temperature-independent diffusion over this range and revert to temperature dependent diffusion on cell membrane blebs, in cells depleted of cholesterol, and upon acute perturbation of actin dynamics and myosin activity. A model transmembrane protein with a cytosolic actin-binding domain also exhibits the temperature-independent behavior, directly implicating the role of cortical actin. We show that diffusion of GPI-anchored proteins also becomes temperature dependent when the filamentous dynamic actin nucleator formin is inhibited. However, changes in cortical actin mesh size or perturbation of branched actin nucleator Arp2/3 do not affect this behavior. Thus cell surface diffusion of GPI anchored proteins and transmembrane proteins that associate with actin is driven by active fluctuations of dynamic cortical actin filaments in addition to thermal fluctuations, consistent with expectations from an "active actin-membrane composite" cell surface. PMID- 26378259 TI - Systemic Administration of Human Bone Marrow-Derived Mesenchymal Stromal Cell Extracellular Vesicles Ameliorates Aspergillus Hyphal Extract-Induced Allergic Airway Inflammation in Immunocompetent Mice. AB - An increasing number of studies demonstrate that administration of either conditioned media (CM) or extracellular vesicles (EVs) released by mesenchymal stromal cells (MSCs) derived from bone marrow and other sources are as effective as the MSCs themselves in mitigating inflammation and injury. The goal of the current study was to determine whether xenogeneic administration of CM or EVs from human bone marrow-derived MSCs would be effective in a model of mixed Th2/Th17, neutrophilic-mediated allergic airway inflammation, reflective of severe refractory asthma, induced by repeated mucosal exposure to Aspergillus hyphal extract (AHE) in immunocompetent C57Bl/6 mice. Systemic administration of both CM and EVs isolated from human and murine MSCs, but not human lung fibroblasts, at the onset of antigen challenge in previously sensitized mice significantly ameliorated the AHE-provoked increases in airway hyperreactivity (AHR), lung inflammation, and the antigen-specific CD4 T-cell Th2 and Th17 phenotype. Notably, both CM and EVs from human MSCs (hMSCs) were generally more potent than those from mouse MSCs (mMSCs) in most of the outcome measures. The weak cross-linking agent 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride was found to inhibit release of both soluble mediators and EVs, fully negating effects of systemically administered hMSCs but only partly inhibited the ameliorating effects of mMSCs. These results demonstrate potent xenogeneic effects of CM and EVs from hMSCs in an immunocompetent mouse model of allergic airway inflammation and they also show differences in mechanisms of action of hMSCs versus mMSCs to mitigate AHR and lung inflammation in this model. SIGNIFICANCE: There is a growing experience demonstrating benefit of mesenchymal stromal cell (MSC)-based cell therapies in preclinical models of asthma. In the current study, conditioned media (CM) and, in particular, the extracellular vesicle fraction obtained from the CM were as potent as the MSCs themselves in mitigating Th2/Th17-mediated allergic airway inflammation in a mouse model of severe refractory clinical asthma. Moreover, human MSC CM and extracellular vesicles were effective in this immunocompetent mouse model. These data add to a growing scientific basis for initiating clinical trials of MSCs or extracellular vesicles derived from MSCs in severe refractory asthma and provide further insight into the mechanisms by which the MSCs may ameliorate the asthma. PMID- 26378260 TI - Oral Mucosal Lamina Propria-Progenitor Cells Exert Antibacterial Properties via the Secretion of Osteoprotegerin and Haptoglobin. AB - The oral cavity possesses a diverse microflora, yet recurrent infections within healthy individuals are rare. Wound healing within the buccal mucosa is preferential, potentially because of the presence of oral mucosal lamina propria progenitor cells (OMLP-PCs). In addition to their multipotency, OMLP-PCs demonstrate potent immunosuppressive properties. The present study investigated whether OMLP-PCs possess antibacterial properties, directly interacting with microorganisms and contributing to the maintenance of a balanced oral microflora. Gram-positive and -negative bacteria were cocultured with OMLP-PCs, buccal mucosal fibroblasts, or their respective conditioned media (CM). Bacterial growth was significantly inhibited when cocultured with OMLP-PCs or their CM. No antibacterial activity was apparent within the fibroblasts. Analysis of the OMLP PC CM indicated constitutive secretion of osteoprotegerin (OPG) and haptoglobin (Hp). Exposure of the bacteria to OPG or Hp demonstrated their differential antibacterial properties, with neutralization/blocking studies confirming that the growth of Gram-positive bacteria was partially restored by neutralizing OPG within OMLP-PC CM; blocking Hp restored the growth of Gram-negative bacteria. The present study demonstrates, for the first time, the broad-spectrum antibacterial properties of OMLP-PCs. We report the direct and constitutive antibacterial nature of OMLP-PCs, with retention of this effect within the CM suggesting a role for soluble factors such as OPG and Hp. Knowledge of the immunomodulatory and antibacterial properties of these cells could potentially be exploited in the development of novel cell- or soluble factor-based therapeutics for the treatment of infectious diseases such as pneumonia or ailments such as chronic nonhealing wounds. SIGNIFICANCE: Oral mucosal lamina propria-progenitor cells (OMLP-PCs) are a cell source with known immunomodulatory properties. The present report demonstrates the novel finding that OMLP-PCs possess potent antibacterial properties, halting the growth of Gram-positive and -negative bacteria through the secretion of soluble factors. OMLP-PCs constitutively secrete osteoprotegerin (OPG) and haptoglobin (Hp) at levels high enough to exert antibacterial action. OPG, a glycoprotein not previously known to be antibacterial, can suppress Gram positive bacterial growth. Hp is only active against Gram-negative microorganisms. These findings indicate that OMLP-PCs could offer great potential in the development of novel cell- or soluble factor-based therapies for the treatment of infectious illness, such as bacterial pneumonia, through systemic infusion and of chronic wounds through local administration. PMID- 26378261 TI - Structural Changes in N-Glycans on Induced Pluripotent Stem Cells Differentiating Toward Cardiomyocytes. AB - Cell-surface glycans vary widely, depending on cell properties. Previously, we reported that the pattern of N-glycan expression on murine induced pluripotent stem cells (iPSCs) changed toward that of the cardiac tissue during cardiomyogenic differentiation. In this study, N-glycans were isolated from human iPSCs, iPSC-derived cardiomyocytes (iPSC-CMs), and human cardiomyocytes (hCMCs). Their structures were analyzed by a mapping technique based on high-performance liquid chromatography elution positions and matrix-assisted laser desorption/ionization time-of-flight mass-spectrometric data. Of 52 isolated N glycans, the structures of 38 were clearly identified. In addition, 11 structures were partially identified because the binding style and fucose binding site at the nonreduced terminal could not be identified. Quantitation of each type of N glycan, based on the terminal glycosylation process, revealed that the exposed N acetylglucosamine (GlcNAc) and the nonreduced terminal fucose types decreased, whereas the exposed galactose or the alpha2-3 NeuAc types increased in the iPSCs during cardiomyogenic differentiation. However, the bisecting GlcNAc and the triantennary structures were found in relative abundance in the iPSC-CMs in comparison with hCMCs or iPSCs. Expression of MGAT3, a glycosyltransferase encoding gene that produces the bisecting GlcNAc structures, was higher in iPSCs and iPSC-CMs than in hCMCs. These findings will prove useful in understanding the directional precision of cardiomyogenic differentiation in vitro. SIGNIFICANCE: This study focused on N-glycans produced in human induced pluripotent stem cells (iPSCs) and iPSC-derived cardiomyocytes to investigate their change on cardiomyogenic differentiation in vitro. This shows that the expression pattern of N-glycans in human iPSCs changed toward the pattern observed in human cardiomyocytes upon cardiomyogenic differentiation. Structural differences were also observed in the bisecting N-acetylglucosamine and the triantennary structures upon cardiomyogenic differentiation. The findings of this study will help in understanding the directional precision of cardiomyogenic differentiation in vitro. PMID- 26378262 TI - Painful and multiple anogenital lesions are common in men with Treponema pallidum PCR-positive primary syphilis without herpes simplex virus coinfection: a cross sectional clinic-based study. AB - BACKGROUND: Chancres, the hallmark of primary syphilis, are classically described as single, painless ulcers at the site of Treponema pallidum inoculation. We aimed to determine the frequency of painful or multiple anogenital lesions of primary syphilis among men, whether there was concurrent herpes simplex virus (HSV) infection and whether HIV status altered clinical presentations. METHODS: This study was conducted among men with T. pallidum PCR-positive lesions, attending a clinic in Melbourne, Australia, between 2009 and 2014. Lesions were also tested with HSV PCR, and syphilis serology undertaken. RESULTS: 183 men with T. pallidum PCR-positive primary anogenital lesions were included. 89% were men who have sex with men, and 10.9% were heterosexual. 38 men (20.8%) were HIV positive. Anal lesions were more common in HIV-positive men (34.2%) than in HIV negative men (11.6%). Primary lesions were frequently painful (49.2%) or multiple (37.7%), and infrequently associated with HSV (2.7%). Of 37 men with both painful and multiple primary lesions, only 8% had concurrent HSV. Presentation was not significantly altered by HIV status. CONCLUSIONS: Primary syphilis lesions are often painful and/or multiple in the absence of herpes coinfection, and may be clinically misdiagnosed. PMID- 26378263 TI - Consumer Choice Between Hospital-Based and Freestanding Facilities for Arthroscopy: Impact on Prices, Spending, and Surgical Complications. AB - BACKGROUND: Hospital-based outpatient departments traditionally charge higher prices for ambulatory procedures, compared with freestanding surgery centers. Under emerging reference-based benefit designs, insurers establish a contribution limit that they will pay, requiring the patient to pay the difference between that contribution limit and the actual price charged by the facility. The purpose of this study was to evaluate the impact of reference-based benefits on consumer choices, facility prices, employer spending, and surgical outcomes for orthopaedic procedures performed at ambulatory surgery centers. METHODS: We obtained data on 3962 patients covered by the California Public Employees' Retirement System (CalPERS) who underwent arthroscopy of the knee or shoulder in the three years prior to the implementation of reference-based benefits in January 2012 and on 2505 patients covered by CalPERS who underwent arthroscopy in the two years after implementation. Control group data were obtained on 57,791 patients who underwent arthroscopy and were not subject to reference-based benefits. The impact of reference-based benefits on consumer choices between hospital-based and freestanding facilities, facility prices, employer spending, and surgical complications was assessed with use of difference-in-differences multivariable regressions to adjust for patient demographic characteristics, comorbidities, and geographic location. RESULTS: By the second year of the program, the shift to reference-based benefits was associated with an increase in the utilization of freestanding ambulatory surgery centers by 14.3 percentage points (95% confidence interval, 8.1 to 20.5 percentage points) for knee arthroscopy and by 9.9 percentage points (95% confidence interval, 3.2 to 16.7 percentage points) for shoulder arthroscopy and a corresponding decrease in the use of hospital-based facilities. The mean price paid by CalPERS fell by 17.6% (95% confidence interval, -24.9% to -9.6%) for knee procedures and by 17.0% (95% confidence interval, -29.3% to -2.5%) for shoulder procedures. The shift to reference-based benefits was not associated with a change in the rate of surgical complications. In the first two years after the implementation of reference-based benefits, CalPERS saved $2.3 million (13%) on these two orthopaedic procedures. CONCLUSIONS: Reference-based benefits increase consumer sensitivity to price differences between freestanding and hospital-based surgical facilities. CLINICAL RELEVANCE: This study shows that the implementation of reference-based benefits does not result in a significant increase in measured complication rates for those subject to reference-based benefits. PMID- 26378264 TI - Computerized Adaptive Tests Detect Change Following Orthopaedic Surgery in Youth with Cerebral Palsy. AB - BACKGROUND: The Cerebral Palsy Computerized Adaptive Test (CP-CAT) is a parent reported outcomes instrument for measuring lower and upper-extremity function, activity, and global health across impairment levels and a broad age range of children with cerebral palsy (CP). This study was performed to examine whether the Lower Extremity/Mobility (LE) CP-CAT detects change in mobility following orthopaedic surgery in children with CP. METHODS: This multicenter, longitudinal study involved administration of the LE CP-CAT, the Pediatric Outcomes Data Collection Instrument (PODCI) Transfer/Mobility and Sports/Physical Functioning domains, and the Timed "Up & Go" test (TUG) before and after elective orthopaedic surgery in a convenience sample of 255 children, four to twenty years of age, who had CP and a Gross Motor Function Classification System (GMFCS) level of I, II, or III. Standardized response means (SRMs) and 95% confidence intervals (CIs) were calculated for all measures at six, twelve, and twenty-four months following surgery. RESULTS: SRM estimates for the LE CP-CAT were significantly greater than the SRM estimates for the PODCI Transfer/Mobility domain at twelve months, the PODCI Sports/Physical Functioning domain at twelve months, and the TUG at twelve and twenty-four months. When the results for the children at GMFCS levels I, II, and III were grouped together, the improvements in function detected by the LE CP CAT at twelve and twenty-four months were found to be greater than the changes detected by the PODCI Transfer/Mobility and Sports/Physical Functioning scales. The LE CP-CAT outperformed the PODCI scales for GMFCS levels I and III at both of these follow-up intervals; none of the scales performed well for patients with GMFCS level II. CONCLUSIONS: The results of this study showed that the LE CP-CAT displayed superior sensitivity to change than the PODCI and TUG scales after musculoskeletal surgery in children with CP. PMID- 26378265 TI - The Fate of Spacers in the Treatment of Periprosthetic Joint Infection. AB - BACKGROUND: Two-stage exchange arthroplasty remains the preferred method to treat periprosthetic joint infection. The aim of this study was to investigate the clinical course of periprosthetic joint infection following resection arthroplasty and insertion of a spacer. METHODS: Our institutional database was used to identify 504 cases of periprosthetic joint infection (326 knees and 178 hips) treated with resection arthroplasty and spacer insertion as part of a two stage exchange arthroplasty. A review of the patient charts was performed to extract information relevant to the objectives of this study that included the details of the clinical course following resection arthroplasty. RESULTS: The mean follow-up duration after initial spacer implantation was 56.2 months. Reimplantation occurred in the joints of 417 (82.7%) of 504 cases. Of these 417 cases, 329 (78.9%) had a minimum one-year follow-up, and 81.4% of these had successful treatment. The mean duration from resection arthroplasty to reimplantation was 4.2 months (range, 0.7 to 131.7 months). Sixty (11.9%) of the 504 joints required interim spacer exchange(s). Of the eighty-seven cases that did not undergo reimplantation, six (6.9%) required amputation, five (5.7%) underwent a Girdlestone procedure, four (4.6%) underwent arthrodesis, and seventy two (82.8%) underwent spacer retention. Thirty-six patients died in the interstage period. CONCLUSIONS: The commonly held belief that two-stage exchange arthroplasty carries a high success rate for the eradication of periprosthetic joint infection may need to be reexamined. A considerable number of patients undergoing the first stage of a two-stage procedure do not undergo a subsequent reimplantation for a variety of reasons or require an additional spacer exchange in the interim. Reports on the success of two-stage exchange should account for the mortality of these patients and for patients who never undergo reimplantation. PMID- 26378266 TI - Thromboembolism After Intramedullary Nailing for Metastatic Bone Lesions. AB - BACKGROUND: The risk of venous thromboembolism (VTE) in patients undergoing intramedullary nailing for skeletal metastatic disease is currently undefined. The purpose of our study was to determine the risk of thromboembolic events, to define the risk factors for VTE, and to define the rate of wound complications in this population. METHODS: A retrospective review of surgical databases at three National Cancer Institute (NCI)-designated cancer centers identified 287 patients with a total of 336 impending or pathologic long-bone fractures that were stabilized with intramedullary nailing between February 2001 and April 2013. Statistical analysis was performed utilizing multivariable logistic regression and Fisher exact tests. RESULTS: The overall rate of VTE was twenty-four (7.1%) of the 336; thirteen (3.9%) were pulmonary embolism (PE), and eleven (3.3%), deep venous thrombosis (DVT). In two patients, adequate anticoagulation data were not available. We found no significant relationship between the type of anticoagulant used and VTE. There was a significant positive correlation found between lung cancer histology and the development of VTE (p < 0.001) or PE (p < 0.001). The absence of radiation therapy approached significance (p = 0.06) with respect to decreased overall VTE risk. Wound complications were documented for 11 (3.3%) of the operations. CONCLUSIONS: There is a high rate of VTE among those with skeletal metastatic disease who undergo intramedullary nailing, even while receiving postoperative thromboembolic prophylaxis. Current anticoagulation protocols may be inadequate. Wound-complication risk with anticoagulant use in this population is low and should not be a deterrent to adequate anticoagulant use for this population. PMID- 26378267 TI - Tibial Plateau Fracture Characteristics: Computed Tomography Mapping of Lateral, Medial, and Bicondylar Fractures. AB - BACKGROUND: Computed tomography (CT) is seen as a useful diagnostic modality in preoperative planning for tibial plateau fractures. The purpose of this study was to characterize patterns of tibial plateau fractures with use of CT mapping. We hypothesized that CT mapping of fractures of the tibial plateau would reveal recurrent patterns of fragments and fracture lines, including patterns that do not fit into Schatzker's original classification. METHODS: One hundred and twenty seven tibial plateau fractures were retrospectively included in this study. Fracture lines and zones of comminution were graphically superimposed onto an axial template of an intact subarticular tibial plateau to identify major patterns of fracture and comminution. This fracture map of the tibial plateau was subsequently divided into lateral (Schatzker types I, II, and III), medial (Schatzker type IV), and bicondylar (Schatzker types V and VI) fracture maps. RESULTS: This study included seventy-three female and fifty-four male patients (average age, forty-seven years [range, seventeen to ninety-one years]) with a tibial plateau fracture. Sixty-four of the fractures were Schatzker type I, II, or III; fifteen were Schatzker type IV; and forty-eight were Schatzker type V or VI. Analysis of the fracture maps suggested patterns in the Schatzker type-IV, V, and VI fractures beyond those described in Schatzker's original classification. The maps of the 127 fractures revealed four recurrent major fracture features: the lateral split fragment (A), found in 75%; the posteromedial fragment (B), seen in 43%; the tibial tubercle fragment (C), seen in 16%; and a zone of comminution that included the tibial spine and frequently extended to the lateral condyle (D), seen in 28%. CONCLUSIONS: Tibial plateau fracture maps show recurrent patterns of fracture lines, revealing four major fracture characteristics. An understanding of these recurrent features of tibial plateau fractures can aid surgeons during diagnosis, preoperative planning, and execution of surgical strategies. PMID- 26378268 TI - Pelvic Fixation in Adult and Pediatric Spine Surgery: Historical Perspective, Indications, and Techniques: AAOS Exhibit Selection. AB - Achieving solid osseous fusion across the lumbosacral junction has historically been, and continues to be, a challenge in spine surgery. Robust pelvic fixation plays an integral role in achieving this goal. The goals of this review are to describe the history of and indications for spinopelvic fixation, examine conventional spinopelvic fixation techniques, and review the newer S2-alar-iliac technique and its outcomes in adult and pediatric patients with spinal deformity. Since the introduction of Harrington rods in the 1960s, spinal instrumentation has evolved substantially. Indications for spinopelvic fixation as a means to achieve lumbosacral arthrodesis include a long arthrodesis (five or more vertebral levels) or use of three-column osteotomies in the lower thoracic or lumbar spine, surgical treatment of high-grade spondylolisthesis, and correction of lumbar deformity and pelvic obliquity. A variety of techniques have been described over the years, including Galveston iliac rods, Jackson intrasacral rods, the Kostuik transiliac bar, iliac screws, and S2-alar-iliac screws. Modern iliac screws and S2-alar-iliac screws are associated with relatively low rates of pseudarthrosis. S2-alar-iliac screws have the advantages of less implant prominence and inline placement with proximal spinal anchors. Collectively, these techniques provide powerful methods for obtaining control of the pelvis in facilitating lumbosacral arthrodesis. PMID- 26378269 TI - High Variability in Outcome Reporting Patterns in High-Impact ACL Literature. AB - BACKGROUND: ACL (anterior cruciate ligament) reconstruction is one of the most commonly performed and studied procedures in modern sports medicine. A multitude of objective and subjective patient outcome measures exists; however, nonstandardized reporting patterns of these metrics may create challenges in objectively analyzing pooled results from different studies. The goal of this study was to document the variability in outcome reporting patterns in high impact orthopaedic studies of ACL reconstruction. METHODS: All clinical studies pertaining to ACL reconstruction in four high-impact-factor orthopaedic journals over a five-year period were reviewed. Biomechanical, basic science, and imaging studies were excluded, as were studies with fewer than fifty patients, yielding 119 studies for review. Incorporation of various objective and subjective outcomes was noted for each study. RESULTS: Substantial variability in reporting of both objective and subjective measures was noted in the study cohort. Although a majority of studies reported instrumented laxity findings, there was substantial variability in the type and method of laxity reporting. Most other objective outcomes, including range of motion, strength, and complications, were reported in <50% of all studies. Return to pre-injury level of activity was infrequently reported (24% of studies), as were patient satisfaction and pain assessment following surgery (8% and 13%, respectively). Of the patient-reported outcomes, the International Knee Documentation Committee (IKDC), Lysholm, and Tegner scores were most often reported (71%, 63%, and 42%, respectively). CONCLUSIONS: Substantial variability in outcome reporting patterns exists among high-impact studies of ACL reconstruction. Such variability may create challenges in interpreting results and pooling them across different studies. PMID- 26378270 TI - What's New in Hip Replacement. PMID- 26378271 TI - Impact of Economic Incentives on Patient Selection of Surgical Facility: Commentary on an article by James C. Robinson, PhD, et al.: "Consumer Choice Between Hospital-Based and Freestanding Facilities for Arthroscopy. Impact on Prices, Spending, and Surgical Complications". PMID- 26378272 TI - Rethinking the Definition of Success in the Management of a Periprosthetic Joint Infection: Commentary on an article by Miguel M. Gomez, MD, et al.: "The Fate of Spacers in the Treatment of Periprosthetic Joint Infection". PMID- 26378273 TI - First Report of Wohlfahrtiimonas chitiniclastica Isolation from a Patient with Cellulitis in the United States. AB - We report the first documented isolation of Wohlfahrtiimonas chitiniclastica from a human in the United States. Initially misidentified as Acinetobacter lwoffii by Vitek-2, the isolate was subsequently identified as W. chitiniclastica by matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and 16S rRNA gene sequencing. While the clinical significance of the isolate in this case is unclear, it highlights the superior performance of MALDI-TOF MS for bacterial identification. PMID- 26378274 TI - Comparative Performance of Three Rapid HBsAg Assays for Detection of HBs Diagnostic Escape Mutants in Clinical Samples. PMID- 26378275 TI - Direct Repeat Unit (dru) Typing of Methicillin-Resistant Staphylococcus pseudintermedius from Dogs and Cats. AB - Methicillin-resistant Staphylococcus pseudintermedius (MRSP) has emerged in a remarkable manner as an important problem in dogs and cats. However, limited molecular epidemiological information is available. The aims of this study were to apply direct repeat unit (dru) typing in a large collection of well characterized MRSP isolates and to use dru typing to analyze a collection of previously uncharacterized MRSP isolates. Two collections of MRSP isolates from dogs and cats were included in this study. The first collection comprised 115 well-characterized MRSP isolates from North America and Europe. The data for these isolates included multilocus sequence typing (MLST) and staphylococcal protein A gene (spa) typing results as well as SmaI macrorestriction patterns after pulsed-field gel electrophoresis (PFGE). The second collection was a convenience sample of 360 isolates from North America. The dru region was amplified by PCR, sequenced, and analyzed. For the first collection, the discriminatory indices of the typing methods were calculated. All isolates were successfully dru typed. The discriminatory power for dru typing (D = 0.423) was comparable to that of spa typing (D = 0.445) and of MLST (D = 0.417) in the first collection. Occasionally, dru typing was able to further discriminate between isolates that shared the same spa type. Among all 475 isolates, 26 different dru types were identified, with 2 predominant types (dt9a and dt11a) among 349 (73.4%) isolates. The results of this study underline that dru typing is a useful tool for MRSP typing, being an objective, standardized, sequence-based method that is relatively cost-efficient and easy to perform. PMID- 26378276 TI - The Race Is On To Shorten the Turnaround Time for Diagnosis of Multidrug Resistant Tuberculosis. AB - To realize the most benefit from multidrug-resistant tuberculosis (MDR-TB) screening, all nucleic acid amplification test (NAAT)-positive respiratory specimens should be universally tested. Once an MDR-TB diagnosis is established, additional testing is warranted to provide details about the detected mutations. The lab-on-chip technology described by A. M. Cabibbe et al. (J Clin Microbiol 53:3876-3880, 2015, http://dx.doi.org/10.1128/JCM.01824-15) potentially provides this much needed information. PMID- 26378277 TI - Metabolomic Profiling of Plasma from Patients with Tuberculosis by Use of Untargeted Mass Spectrometry Reveals Novel Biomarkers for Diagnosis. AB - Although tuberculosis (TB) is a reemerging disease that affects people in developing countries and immunocompromised populations in developed countries, the current diagnostic methods are far from optimal. Metabolomics is increasingly being used for studies on infectious diseases. We performed metabolome profiling of plasma samples to identify potential biomarkers for diagnosing TB. We compared the plasma metabolome profiles of TB patients (n = 46) with those of community acquired pneumonia (CAP) patients (n = 30) and controls without active infection (n = 30) using ultrahigh-performance liquid chromatography-electrospray ionization-quadrupole time of flight mass spectrometry (UHPLC-ESI-QTOFMS). Using multivariate and univariate analyses, four metabolites, 12R-hydroxy-5Z,8Z,10E,14Z eicosatetraenoic acid [12(R)-HETE], ceramide (d18:1/16:0), cholesterol sulfate, and 4alpha-formyl-4beta-methyl-5alpha-cholesta-8-en-3beta-ol, were identified and found to have significantly higher levels in TB patients than those in CAP patients and controls. In a comparison of TB patients and controls, the four metabolites demonstrated area under the receiver operating characteristic curve (AUC) values of 0.914, 0.912, 0.905, and 0.856, sensitivities of 84.8%, 84.8%, 87.0%, and 89.1%, specificities of 90.0%, 86.7%, 86.7%, and 80.0%, and fold changes of 4.19, 26.15, 6.09, and 1.83, respectively. In a comparison of TB and CAP patients, the four metabolites demonstrated AUC values of 0.793, 0.717, 0.802, and 0.894, sensitivities of 89.1%, 71.7%, 80.4%, and 84.8%, specificities of 63.3%, 66.7%, 70.0%, and 83.3%, and fold changes of 4.69, 3.82, 3.75, and 2.16, respectively. 4alpha-Formyl-4beta-methyl-5alpha-cholesta-8-en-3beta-ol combined with 12(R)-HETE or cholesterol sulfate offered >=70% sensitivity and >=90% specificity for differentiating TB patients from controls or CAP patients. These novel plasma biomarkers, especially 12(R)-HETE and 4alpha-formyl-4beta methyl-5alpha-cholesta-8-en-3beta-ol, alone or in combination, are potentially useful for rapid and noninvasive diagnosis of TB. The present findings may offer insights into the pathogenesis and host response in TB. PMID- 26378278 TI - Detection of Polyclonality among Clinical Isolates from Prosthetic Joint Infections. AB - Prosthetic joint infection (PJI) is an increasingly important health concern in the Western world due to the rising number of joint arthroplasties. Although most infections are considered to be monomicrobial, the introduction of sonication procedures has led to an increase in the detection of polymicrobial infections. To date, no published studies have investigated the presence of different clones of the same species in the infected patient. The objective of this study was to analyze whether the phenomenon of polyclonality, or the appearance of different clones in the same sample, occurs in PJI. Bacteria isolated by sonication of the retrieved implant from patients with theoretically monomicrobial PJI were included in the study. Two techniques (random amplified polymorphic DNA [RAPD] and matrix-assisted laser desorption ionization-time of flight [MALDI-TOF] mass spectrometry) were used to determine the presence of several clones in the same sample. Results were analyzed to determine bacterial species and infection type (acute versus chronic). RAPD showed a predominance of polyclonal cases (16 of 19). However, when performing the analysis with MALDI-TOF, all cases were shown to be polyclonal. We were unable to establish any relationship between the two methodologies. Polyclonality is a common phenomenon in acute and chronic PJI. Further studies are needed to establish the potential implications of this phenomenon on patient outcomes. PMID- 26378279 TI - Complete Deletion of the Fucose Operon in Haemophilus influenzae Is Associated with a Cluster in Multilocus Sequence Analysis-Based Phylogenetic Group II Related to Haemophilus haemolyticus: Implications for Identification and Typing. AB - Nonhemolytic variants of Haemophilus haemolyticus are difficult to differentiate from Haemophilus influenzae despite a wide difference in pathogenic potential. A previous investigation characterized a challenging set of 60 clinical strains using multiple PCRs for marker genes and described strains that could not be unequivocally identified as either species. We have analyzed the same set of strains by multilocus sequence analysis (MLSA) and near-full-length 16S rRNA gene sequencing. MLSA unambiguously allocated all study strains to either of the two species, while identification by 16S rRNA sequence was inconclusive for three strains. Notably, the two methods yielded conflicting identifications for two strains. Most of the "fuzzy species" strains were identified as H. influenzae that had undergone complete deletion of the fucose operon. Such strains, which are untypeable by the H. influenzae multilocus sequence type (MLST) scheme, have sporadically been reported and predominantly belong to a single branch of H. influenzae MLSA phylogenetic group II. We also found evidence of interspecies recombination between H. influenzae and H. haemolyticus within the 16S rRNA genes. Establishing an accurate method for rapid and inexpensive identification of H. influenzae is important for disease surveillance and treatment. PMID- 26378280 TI - Diagnostic Accuracy of Seven Commercial Assays for Rapid Detection of Group A Rotavirus Antigens. AB - Seven commercial immunochromatographic assays intended for the detection of group A rotavirus antigens in human stool samples were evaluated. These assays showed similar levels of diagnostic accuracy and were suitable for the detection of rotavirus in patients with acute gastroenteritis but missed some asymptomatic rotavirus shedding identified by real-time reverse transcription-PCR. PMID- 26378281 TI - One-Step Identification of Five Prominent Chicken Salmonella Serovars and Biotypes. AB - Based on bacterial genomic data, we developed a one-step multiplex PCR assay to identify Salmonella and simultaneously differentiate the two invasive avian adapted S. enterica serovar Gallinarum biotypes Gallinarum and Pullorum, and the most frequent, specific, and asymptomatic colonizers of chickens, serovars Enteritidis, Heidelberg, and Kentucky. PMID- 26378282 TI - FilmArray Respiratory Panel Assay: Comparison of Nasopharyngeal Swabs and Bronchoalveolar Lavage Samples. AB - The FilmArray respiratory panel (FARP) reliably and rapidly identifies 17 viruses and 3 bacterial pathogens. A nasopharyngeal swab FARP (NP FARP) is performed for many patients with respiratory symptoms. For patients who are acutely ill or immunocompromised or fail to improve, a bronchoalveolar lavage sample FARP (BAL FARP) is performed in addition to the NP FARP. To date, no studies have compared the yield of a BAL FARP with that of an NP FARP. We retrospectively studied all patients who had a BAL FARP within 7 days after an NP FARP between June 2013 and May 2014. Demographic information, comorbidities, FARP results, and all microbiologic data from BAL fluid were collected. Eighty-six patients had a BAL FARP performed within 7 days (mean, 1.6; median, 1) after an NP FARP. Of these, 66 (77%) had concordant BAL and NP FARP results: 15 (23%) had the same pathogen identified from the NP and BAL FARPs, and 51 (77%) had concordant negative FARP results. In 18 of the 86 patients (21%), a pathogen was detected from the NP FARP; of these, 15 (83%) had a concordant match on a subsequent BAL FARP, and the remaining 3 had negative BAL FARPs. In 17 of the 86 patients (20%), pathogens were identified from the BAL FARPs that were not detected by the NP FARPs; of these, 16 (94%) had initial negative NP FARPs. The data suggest that once a pathogen is identified by an NP FARP, a subsequent BAL FARP is unlikely to add new microbiologic information. However, a BAL FARP may provide new, useful microbiologic information when performed within 7 days after a negative NP FARP. PMID- 26378283 TI - Rapid Detection of Subtype H10N8 Influenza Virus by One-Step Reverse Transcription-Loop-Mediated Isothermal Amplification Methods. AB - We developed hemagglutinin- and neuraminidase-specific one-step reverse transcription-loop-mediated isothermal amplification assays for detecting the H10N8 virus. The detection limit of the assays was 10 copies of H10N8 virus, and the assays did not amplify nonspecific RNA. The assays can detect H10N8 virus from chicken samples with high sensitivity and specificity, and they can serve as an effective tool for detecting and monitoring H10N8 virus in live poultry markets. PMID- 26378285 TI - Successful Treatment of Peritoneal Dialysis Catheter-Related Polymicrobial Peritonitis Involving Clostridium difficile. AB - Clostridium difficile is one of the most common nosocomial pathogens and the cause of pseudomembranous colitis in cases of prior antimicrobial exposure. Extraintestinal manifestations of C. difficile are uncommon and rarely reported. We report the first successfully treated case of catheter-related C. difficile peritonitis in a patient undergoing peritoneal dialysis. PMID- 26378284 TI - Improved Detection by Next-Generation Sequencing of Pyrazinamide Resistance in Mycobacterium tuberculosis Isolates. AB - The technical limitations of common tests used for detecting pyrazinamide (PZA) resistance in Mycobacterium tuberculosis isolates pose challenges for comprehensive and accurate descriptions of drug resistance in patients with multidrug-resistant tuberculosis (MDR-TB). In this study, a 606-bp fragment (comprising the pncA coding region plus the promoter) was sequenced using Ion Torrent next-generation sequencing (NGS) to detect associated PZA resistance mutations in 88 recultured MDR-TB isolates from an archived series collected in 2001. These 88 isolates were previously Sanger sequenced, with 55 (61%) designated as carrying the wild-type pncA gene and 33 (37%) showing mutations. PZA susceptibility of the isolates was also determined using the Bactec 460 TB system and the Wayne test. In this study, isolates were recultured and susceptibility testing was performed in Bactec 960 MGIT. Concordance between NGS and MGIT results was 93% (n = 88), and concordance values between the Bactec 460, the Wayne test, or pncA gene Sanger sequencing and NGS results were 82% (n = 88), 83% (n = 88), and 89% (n = 88), respectively. NGS confirmed the majority of pncA mutations detected by Sanger sequencing but revealed several new and mixed-strain mutations that resolved discordancy in other phenotypic results. Importantly, in 53% (18/34) of these isolates, pncA mutations were located in the 151 to 360 region and warrant further exploration. In these isolates, with their known resistance to rifampin, NGS of pncA improved PZA resistance detection sensitivity to 97% and specificity to 94% using NGS as the gold standard and helped to resolve discordant results from conventional methodologies. PMID- 26378286 TI - Determination of Disk Diffusion and MIC Quality Control Guidelines for Solithromycin, a Novel Fluoroketolide Antibacterial, against Neisseria gonorrhoeae. AB - This solithromycin quality control study was performed to establish quality control (QC) ranges for the N. gonorrhoeae ATCC 49226 control strain for MIC agar dilution testing (AD) and zones by disk diffusion testing (DD). The following ranges were established: AD, 0.03 to 0.25 MUg/ml, and DD, 33 to 43 mm. In January 2015, the CLSI Subcommittee on Antimicrobial Susceptibility Testing approved these ranges, which will be important when evaluating solithromycin against clinical isolates of N. gonorrhoeae. PMID- 26378287 TI - First Polish Conference on Sarcoidosis. PMID- 26378288 TI - Carbohydrate-Based Vaccines. Preface. PMID- 26378289 TI - Foreword. PMID- 26378290 TI - Negative pressure wound therapy with instillation: past, present, and future. AB - Negative pressure wound therapy with instillation (NPWTi) is a novel treatment option that provides the combination of negative pressure with intermittent instillation of a solution. Standard Negative Pressure Wound Therapy (NPWT) is an established adjunctive treatment option that offers the ability to promote granulation tissue in wounds. However, there is limited evidence for its utility in the environment of active or senescent infection. Wounds that are acutely infected or that contain deleterious biofilm are a challenging problem, which require an intensive multimodal approach including antibiosis, surgical intervention, and local wound care. Adjunctive application of NPWTi can potentially expedite clearance of infection and wound closure. Although this technology has been commercially available for over a decade, its adoption has been limited. Recently, there has been a resurgence of interest in this therapy with emerging evidence from animal models as well as human clinical studies. There are remaining questions regarding NPWTi including the selection of the optimal instillation solution and device settings. This article discusses the past development, current knowledge, and future direction of NPWTi. PMID- 26378291 TI - A winter's tale. PMID- 26378292 TI - Author response. PMID- 26378293 TI - Author response. PMID- 26378294 TI - Editorial. PMID- 26378295 TI - Notes on a puzzle piece. PMID- 26378296 TI - The golden age of bio-logging: how animal-borne sensors are advancing the frontiers of ecology. AB - Great leaps forward in scientific understanding are often spurred by innovations in technology. The explosion of miniature sensors that are driving the boom in consumer electronics, such as smart phones, gaming platforms, and wearable fitness devices, are now becoming available to ecologists for remotely monitoring the activities of wild animals. While half a century ago researchers were attaching balloons to the backs of seals to measure their movement, today ecologists have access to an arsenal of sensors that can continuously measure most aspects of an animal's state (e.g., location, behavior, caloric expenditure, interactions with other animals) and external environment (e.g., temperature, salinity, depth). This technology is advancing our ability to study animal ecology by allowing researchers to (1) answer questions about the physiology, behavior, and ecology of wild animals in situ that would have previously been limited to tests on model organisms in highly controlled settings, (2) study cryptic or wide-ranging animals that have previously evaded investigation, and (3) develop and test entirely new theories. Here we explore how ecologists are using these tools to answer new questions about the physiological performance, energetics, foraging, migration, habitat selection, and sociality of wild animals, as well as collect data on the environments in which they live. PMID- 26378297 TI - Phenological synchronization drives demographic rates of populations. AB - Phenology is increasingly recognized as an important factor structuring communities because it determines when and at what life stage organisms interact. Previous work indicates that changes in first or mean timing of a phenological event can affect populations and communities, but little is known about the consequences of changes in the distribution (e.g., synchrony) of a phenological event. We conducted an experiment using an anuran study system to determine how synchrony of reproduction and egg hatching affects offspring performance, whether the effects are density dependent, and how hatching synchrony influences the synchrony of a subsequent phenological event (metamorphosis). Changes in hatching synchrony altered survival, development rates, and body size at metamorphosis, which can affect post-metamorphosis performance. The degree of synchrony at hatching also affected the degree of synchrony at metamorphosis, indicating that timing of one stage can carry over to affect that of later ones. Importantly, these effects were all density dependent, likely because decreasing hatching synchrony switched intraspecific interactions from scramble to contest competition. This study demonstrates that phenological synchrony has important consequences for ecological interactions and population dynamics, emphasizing the need to develop a comprehensive understanding of how shifts in phenological distributions affect communities. PMID- 26378298 TI - Habitat restoration affects immature stages of a wetland butterfly through indirect effects on predation. AB - Habitat loss worldwide has led to the widespread use of restoration practices for the recovery of imperiled species. However, recovery success may be hampered by focusing on plant communities, rather than the complex suite of direct and indirect interactions among trophic levels that occur in natural systems. Through a factorial field experiment, we tested the effects of wetland restoration on egg and juvenile survival of a locally rare butterfly, Satyrodes appalachia, via tree removal and damming. Tree removal more than tripled S. appalachia host plant abundance, but neither restoration action directly affected S. appalachia egg and juvenile survival. Instead, we found strong indirect effects of habitat manipulation on S. appalachia egg and juvenile survival that were mediated through predation. The interaction of tree removal and damming significantly decreased predation of S. appalachia eggs relative to each treatment alone. Damming alone had a significant positive indirect effect on the survival of S. appalachia juveniles, likely because increases in standing water reduced predator access. Our results emphasize the need for experiments that evaluate the demographic responses of imperiled species to habitat restoration prior to management action and quantify potential indirect effects mediated through higher trophic levels. PMID- 26378299 TI - Mycorrhizal response trades off with plant growth rate and increases with plant successional status. AB - Early-successional plant species invest in rapid growth and reproduction in contrast to slow growing late-successional species. We test the consistency of "trade-offs between plant life history and responsiveness on arbuscular mycorrhizal fungi. We selected four very early-, seven early-, 11 middle-, and eight late-successional plant species from six different families and functional groups and grew them with and without a mixed fungal inoculum and compared root architecture, mycorrhizal responsiveness, and plant growth rate. Our results indicate mycorrhizal responsiveness increases with plant successional stage and that this effect explains more variation in mycorrhizal response than is explained by phylogenetic relatedness. The mycorrhizal responsiveness of individual plant species was positively correlated with mycorrhizal root infection and negatively correlated with average plant mass and the number of root tips per unit mass, indicating that both plant growth rate and root architecture trade off with investment in mycorrhizal mutualisms. Because late successional plants are very responsive to mycorrhizal fungi, our results suggest that fungal community dynamics may be an important driver of plant succession. PMID- 26378300 TI - Geomorphology controls the trophic base of stream food webs in a boreal watershed . AB - Abstract. Physical attributes of rivers control the quantity and quality of energy sources available to consumers, but it remains untested whether geomorphic conditions of whole watersheds affect the assimilation of different resources by stream organisms. We compared the fatty acid (FA) compositions of two invertebrate taxa (caddisflies, mayflies) collected from 16 streams in southwest Alaska, USA, to assess how assimilation of terrestrial organic matter (OM) and algae varied across a landscape gradient in watershed features. We found relatively higher assimilation of algae in high-gradient streams compared with low-gradient streams, and the opposite pattern for assimilation of terrestrial OM and microbes. The strength of these patterns was more pronounced for caddisflies than mayflies. Invertebrates from low-gradient watersheds had FA markers unique to methane-oxidizing bacteria and sulfate-reducing microbes, indicating a contribution of anaerobic pathways to primary consumers. Diversity of FA composition was highest in watersheds of intermediate slopes that contain both significant terrestrial inputs as well as high algal biomass. By controlling the accumulation rate and processing of terrestrial OM, watershed features influence the energetic base of food webs in boreal streams. PMID- 26378301 TI - Using multispecies occupancy models to improve the characterization and understanding of metacommunity structure. AB - Two of the most prominent frameworks to develop in ecology over the past decade are metacommunity ecology, which seeks to characterize multispecies distributions across space, and occupancy modeling, which corrects for imperfect detection in an effort to better understand species occurrence patterns. Although their goals are complementary, metacommunity theory and statistical occupancy modeling methods have developed independently. For instance, the elements of metacommunity structure (EMS) framework uses species occurrence data to classify metacommunity structure and link it to underlying environmental gradients. While the efficacy of this approach relies on the quality of the data, few studies have considered how imperfect detection, which is widespread in ecological surveys and the major focus of occupancy modeling, affects the outcome. We introduce a framework that integrates multispecies occupancy models with the current EMS framework, detection error-corrected EMS (DECEMS). This method offers two distinct advantages. First, DECEMS reduces bias in characterizing metacommunity structure by using repeated surveys and occupancy models to disentangle species-specific occupancy and detection probabilities, ultimately bringing metacommunity structure classification into a more probabilistic framework. Second, occupancy modeling allows estimation of species-specific responses to environmental covariates, which will increase our ability to link species-level effects to metacommunity-wide patterns. After reviewing the EMS framework, we introduce a simple multispecies occupancy model and show how DECEMS can work in practice, highlighting that detection error often causes EMS to assign incorrect structures. To emphasize the broader applicability of this approach, we further illustrate that DECEMS can reduce the rate of structure misclassification by more than 20% in some cases, even proving useful when detection error rates are quite low (-10%). Integrating occupancy models and the EMS framework will lead to more accurate descriptions of metacommunity structure and to a greater understanding of the mechanisms by which different structures arise. PMID- 26378302 TI - Bison distribution under conflicting foraging strategies: site fidelity vs. energy maximization. AB - Foraging strategies based on site fidelity and maximization of energy intake rate are two adaptive forces shaping animal behavior. Whereas these strategies can both be evolutionarily stable, they predict conflicting optimal behaviors when population abundance is in decline. In such a case, foragers employing an energy maximizing strategy should reduce their use of low-quality patches as interference competition becomes less intense for high-quality patches. Foragers using a site fidelity strategy, however, should continue to use familiar patches. Because natural fluctuations in population abundance provide the only non manipulative opportunity to evaluate adaptation to these evolutionary forces, few studies have examined these foraging strategies simultaneously. Using abundance and space use data from a free-ranging bison (Bison bison) population living in a meadow-forest matrix in Prince Albert National Park, Canada, we determined how individuals balance the trade-off between site fidelity and energy-maximizing patch choice strategies with respect to changes in population abundance. From 1996 to 2005, bison abundance increased from 225 to 475 and then decreased to 225 by 2013. During the period of population increase, population range size increased. This expansion involved the addition of relatively less profitable areas and patches, leading to a decrease in the mean expected profitability of the range. Yet, during the period of population decline, we detected neither a subsequent retraction in population range size nor an increase in mean expected profitability of the range. Further, patch selection models. during the population decline indicated that, as density decreased, bison portrayed stronger fidelity to previously visited meadows, but no increase in selection strength for profitable meadows. Our analysis reveals that an energy-maximizing patch choice strategy alone cannot explain the distribution ofindividuals and populations, and site fidelity is an important evolutionary force shaping animal distribution. Animals may not always forage in the richest patches available, as ecological theory would often predict, but their use of profitable patches is dependent on population dynamics and the strength of site fidelity. Our findings are likewise relevant to applied inquiries such as forecasting species range shifts and reducing human-wildlife conflicts. PMID- 26378303 TI - Stochastic dynamics of a warmer Great Barrier Reef. AB - Pressure on natural communities from human activities continues to increase. Even unique ecosystems like the Great Barrier Reef (GBR), that until recently were considered near-pristine and well-protected, are showing signs of rapid degradation. We collated recent (1996-2006) spatiotemporal relationships between benthic community composition on the GBR and environmental variables (ocean temperature and local threats resulting from human activity). We built multivariate models of the effects of these variables on short-term dynamics, and developed an analytical approach to study their long-term consequences. We used this approach to study the effects of ocean warming under different levels of local threat. Observed short-term changes in benthic community structure (e.g., declining coral cover) were associated with ocean temperature (warming) and local threats. Our model projected that, in the long-term, coral cover of less than 10% was not implausible. With increasing temperature and/or local threats, corals were initially replaced by sponges, gorgonians, and other taxa, with an eventual moderately high probability of domination (> 50%) by macroalgae when temperature increase was greatest (e.g., 3.5 degrees C of warming). Our approach to modeling community dynamics, based on multivariate statistical models, enabled us to project how environmental change (and thus local and international policy decisions) will influence the future state of coral reefs. The same approach could be applied to other systems for which time series of ecological and environmental variables are available. PMID- 26378304 TI - Stability of Caribbean coral communities quantified by long-term monitoring and autoregression models. AB - Tropical coral reefs exemplify ecosystems imperiled by environmental change. Anticipating the future of reef ecosystems requires understanding how scleractinian corals respond to the multiple environmental disturbances that threaten their survival. We analyzed the stability of coral reefs at three habitats at different depths along the south shore of St. John, U.S. Virgin Islands, using multivariate autoregression (MAR) models and two decades of monitoring data. We quantified several measures of ecosystem stability, including the magnitude of typical stochastic fluctuations, the rate of recovery following disturbance, and the sensitivity of coral cover to hurricanes and elevated sea temperature. Our results show that, even within a -4 km shore, coral communities in different habitats display different stability properties, and that the stability of each habitat corresponds with the habitat's known synecology. Two Orbicella-dominated habitats are less prone to annual stochastic fluctuations than coral communities in shallower water, but they recover slowly from disturbance, and one habitat has suffered recent losses in scleractinian cover that will not be quickly reversed. In contrast, a shallower, low-coral-cover habitat is subject to greater stochastic fluctuations, but rebounds more quickly from disturbance and is more robust to hurricanes and seawater warming. In some sense, the shallower community is more stable, although the stability arguably arises from having little coral cover left. Our results sharpen understanding of recent changes in coral communities at these habitats, provide a more detailed understanding of how these habitats may change in future environments, and illustrate how MAR models can be used to assess stability of communities founded upon long-lived species. PMID- 26378305 TI - Neighborhood diversity of large trees shows independent species patterns in a mixed dipterocarp forest in Sri Lanka. AB - Interactions among neighboring individuals influence plant performance and should create spatial patterns in local community structure. In order to assess the role of large trees in generating spatial patterns in local species richness, we used the individual species-area relationship (ISAR) to evaluate the species richness of trees of different size classes (and dead trees) in circular neighborhoods with varying radius around large trees of different focal species. To reveal signals of species interactions, we compared the ISAR function of the individuals of focal species with that of randomly selected nearby locations. We expected that large trees should strongly affect the community structure of smaller trees in their neighborhood, but that these effects should fade away with increasing size class. Unexpectedly, we found that only few focal species showed signals of species interactions with trees of the different size classes and that this was less likely for less abundant focal species. However, the few and relatively weak departures from independence were consistent with expectations of the effect of competition for space and the dispersal syndrome on spatial patterns. A noisy signal of competition for space found for large trees built up gradually with increasing life stage; it was not yet present for large saplings but detectable for intermediates. Additionally, focal species with animal-dispersed seeds showed higher species richness in their neighborhood than those with gravity- and gyration-dispersed seeds. Our analysis across the entire ontogeny from recruits to large trees supports the hypothesis that stochastic effects dilute deterministic species interactions in highly diverse communities. Stochastic dilution is a consequence of the stochastic geometry of biodiversity in species rich communities where the identities of the nearest neighbors of a given plant are largely unpredictable. While the outcome of local species interactions is governed for each plant by deterministic fitness and niche differences, the large variability of competitors causes also a large variability in the outcomes of interactions and does not allow for strong directed responses at the species level. Collectively, our results highlight the critical effect of the stochastic geometry of biodiversity in structuring local spatial patterns of tropical forest diversity. PMID- 26378306 TI - Scale dependence of disease impacts on quaking aspen (Populus tremuloides) mortality in the southwestern United States. AB - Depending on how disease impacts tree exposure to risk, both the prevalence of disease and disease effects on survival may contribute to patterns of mortality risk across a species' range. Disease may accelerate tree species' declines in response to global change factors, such as drought, biotic interactions, such as competition, or functional traits, such as allometry. To assess the role of disease in mediating mortality risk in quaking aspen (Populus tremuloides), we developed hierarchical Bayesian models for both disease prevalence in live aspen stems and the resulting survival rates of healthy and diseased aspen near the species' southern range limit using 5088 individual trees on 281 United States Forest Service Forest Inventory and Analysis plots in the southwestern United States. We found that disease prevalence depended primarily on tree size, tree allometry, and spatial variation in precipitation, while mortality depended on tree size, allometry, competition, spatial variation in summer temperature, and both temporal and spatial variation in summer precipitation. Disease prevalence was highest in large trees with low slenderness found on dry sites. For healthy trees, mortality decreased with diameter, slenderness, and temporal variation in summer precipitation, but increased with competition and spatial variation in summer temperature. Mortality of diseased trees decreased with diameter and aspen relative basal area and increased with mean summer temperature and precipitation. Disease infection increased aspen mortality, especially in trees of intermediate size and trees on plots at climatic extremes (i.e., cool, wet and warm, dry climates). By examining variation in disease prevalence, mortality of healthy trees, and mortality of diseased trees, we showed that the role of disease in aspen tree mortality depended on the scale of inference. For variation among individuals in diameter, disease tended to expose intermediate-size trees experiencing moderate risk to greater risk. For spatial variation in summer temperature, disease exposed lower risk populations to greater mortality probabilities, but the magnitude of this exposure depended on summer precipitation. Furthermore, the importance of diameter and slenderness in mediating responses to climate supports the increasing emphasis on trait variation in studies of ecological responses to global change. PMID- 26378307 TI - Low-severity fire increases tree defense against bark beetle attacks. AB - Induced defense is a common plant strategy in response to herbivory. Although abiotic damage, such as physical wounding, pruning, and heating, can induce plant defense, the effect of such damage by large-scale abiotic disturbances on induced defenses has not been explored and could have important consequences for plant survival facing future biotic disturbances. Historically, low-severity wildfire was a widespread, frequent abiotic disturbance in many temperate coniferous forests. Native Dendroctonus and Ips bark beetles are also a common biotic disturbance agent in these forest types and can influence tree mortality patterns after wildfire. Therefore, species living in these disturbance-prone environments with strategies to survive both frequent fire and bark beetle attack should be favored. One such example is Pinus ponderosa forests of western North America. These forests are susceptible to bark beetle attack and frequent, low-severity fire was common prior to European settlement. However, since the late 1800s, frequent, low-severity fires have greatly decreased in these forests. We hypothesized that non-lethal, low-severity, wildfire induces resin duct defense in P. ponderosa and that lack of low-severity fire relaxes resin duct defense in forests dependent on frequent, low-severity fire. We first compared axial resin duct traits between trees that either survived or died from bark beetle attacks. Next, we studied axial ducts using tree cores with crossdated chronologies in several natural P. ponderosa stands before and after an individual wildfire and, also, before and after an abrupt change in fire frequency in the 20th century. We show that trees killed by bark beetles invested less in resin ducts relative to trees that survived attack, suggesting that resin duct-related traits provide resistance against bark beetles. We then show low-severity fire induces resin duct production, and finally, that resin duct production declines when fire ceases. Our results demonstrate that low-severity fire can trigger a long-lasting induced defense that may increase tree survival from subsequent herbivory. PMID- 26378308 TI - Freezing temperatures as a limit to forest recruitment above tropical Andean treelines. AB - The elevation of altitudinal treelines is generally believed to occur where low mean temperatures during the growing season limit growth and prevent trees from establishing at higher elevations. Accordingly, treelines should move upslope with increasing global temperatures. Contrary to this prediction, tropical treelines have remained stable over the past several decades despite increasing mean temperatures. The observed stability of tropical treelines, coupled with the drastically different temperature profiles between temperate and tropical treelines, suggests that using mean measures of temperature to predict tropical treeline movements during climate change may be overly simplistic. We hypothesize that frost events at tropical treelines may slow climate driven treeline movement by preventing tree recruitment beyond the established forest canopy. To assess this hypothesis, we measured freezing resistance of four canopy-forming treeline species (Weinmannia fagaroides, Polylepis pauta, Clethra cuneata, and Gynoxys nitida) at two life stages (juvenile and adult) and during two seasons (warm-wet and cold-dry). Freezing resistances were then compared to microclimatic data to determine if freezing events in the grassland matrix above treeline are too harsh for these forest species. Freezing resistance varied among species and life stages from -5.7 degrees C for juveniles of P. pauta to -11.1 degrees C for juveniles of W. fagaroides. Over a four-year period, the lowest temperatures recorded at 10 cm above ground level in the grasslands above treeline and at treeline itself were -8.9 degrees C and -6.8 degrees C, respectively. Juveniles maintained freezing resistances similar to adults during the coldest parts of the year and ontogenetic differences in freezing resistance were only present during the warm season when temperatures did not represent a significant threat to active plant tissue. These findings support the hypothesis that rare extreme freezing events at and above tropical treelines can prevent recruitment outside of closed canopy forest for some tree species and may significantly slow treeline advancement despite warming mean temperatures. Predictions of treeline shifts under climate change should be reevaluated to include species-specific' climatic tolerances and measures of climatic variability. PMID- 26378309 TI - Lianas always outperform tree seedlings regardless of soil nutrients: results from a long-term fertilization experiment. AB - Lianas are a prominent growth form in tropical forests, and there is compelling evidence that they are increasing in abundance throughout the Neotropics. While recent evidence shows that soil resources limit tree growth even in deep shade, the degree to which soil resources limit lianas in forest understories, where they coexist with trees for decades, remains unknown. Regardless, the physiological underpinnings of soil resource limitation in deeply shaded tropical habitats remain largely unexplored for either trees or lianas. Theory predicts that lianas should be more limited by soil resources than trees because they occupy the quick-return end of the "leaf economic spectrum," characterized by high rates of photosynthesis, high specific leaf area, short leaf life span, affinity to high-nutrient sites, and greater foliar nutrient concentrations. To address these issues, we asked whether soil resources (nitrogen, phosphorus, and potassium), alone or in combination, applied experimentally for more than a decade would cause significant changes in the morphology or physiology of tree and liana seedlings in a lowland tropical forest. We found evidence for the first time that phosphorus limits the photosynthetic performance of both trees and lianas in deeply shaded understory habitats. More importantly, lianas always showed significantly greater photosynthetic capacity, quenching, and saturating light levels compared to trees across all treatments. We found little evidence for nutrient x growth form interactions, indicating that lianas were not disproportionately favored in nutrient-rich habitats. Tree and liana seedlings differed markedly for six key morphological traits, demonstrating that architectural differences occurred very early in ontogeny prior to lianas finding a trellis (all seedlings were self-supporting). Overall, our results do not support nutrient loading as a mechanism of increasing liana abundance in the Neotropics. Rather, our finding that lianas always outperform trees, in terms of photosynthetic processes and under contrasting rates of resource supply of macronutrients, will allow lianas to increase in abundance if disturbance and tree turnover rates are increasing in Neotropical forests as has been suggested. PMID- 26378310 TI - How functional traits, herbivory, and genetic diversity interact in Echinacea: implications for fragmented populations. AB - Habitat fragmentation produces small, spatially isolated populations that promote inbreeding. Remnant populations often contain inbred and outbred individuals, but it is unclear how inbreeding relative to outbreeding affects the expression of functional traits and biotic interactions such as herbivory. We measured a suite of 12 functional traits and herbivore damage on three genotypic cross types in the prairie forb, Echinacea angustifolia: inbred, and outbred crosses resulting from matings within and between remnant populations. Inbreeding significantly affected the expression of all 12 functional traits that influence resource capture. Inbred individuals had consistently lower photosynthetic rates, water use efficiencies, specific leaf areas, and had higher trichome numbers, percent C, and percent N than outbred individuals. However, herbivore damage did not differ significantly among the cross types and was not correlated with other leaf functional traits. Leaf architecture and low physiological rates of the inbred compared to outbred individuals imply poorer capture or use of resources. Inbred plants also had lower survival and fitness relative to outbred plants. Our results show that inbreeding, a phenomenon predicted and observed to occur in fragmented populations, influences key functional traits such as plant structure, physiology and elemental composition. Because of their likely role in fitness of individuals and ecological dynamics plant functional traits can serve as a bridge between evolution and community or ecosystem ecology. PMID- 26378311 TI - Predator cannibalism can intensify negative impacts on heterospecific prey. AB - Although natural populations consist of individuals with different traits, and the degree of phenotypic variation varies among populations, the impact of phenotypic variation on ecological interactions has received little attention, because traditional approaches to community ecology assume homogeneity of individuals within a population. Stage structure, which is a common way of generating size and developmental variation within predator populations, can drive cannibalistic interactions, which can affect the strength of predatory effects on the predator's heterospecific prey. Studies have shown that predator cannibalism weakens predatory effects on heterospecific prey by reducing the size of the predator population and by inducing less feeding activity of noncannibal predators. We predict, however, that predator cannibalism, by promoting rapid growth of the cannibals, can also intensify predation pressure on heterospecific prey, because large predators have large resource requirements and may utilize a wider variety of prey species. To test this hypothesis, we conducted an experiment in which we created carnivorous salamander (Hynobius retardatus) populations with different stage structures by manipulating the salamander's hatch timing (i.e., populations with large or small variation in the timing of hatching), and explored the resultant impacts on the abundance, behavior, morphology, and life history of the salamander's large heterospecific prey, Rana pirica frog tadpoles. Cannibalism was rare in salamander populations having small hatch-timing variation, but was frequent in those having large hatch-timing variation. Thus, giant salamander cannibals occurred only in the latter. We clearly showed that salamander giants exerted strong predation pressure on frog tadpoles, which induced large behavioral and morphological defenses in the tadpoles and caused them to metamorphose late at large size. Hence, predator cannibalism arising from large variation in the timing of hatching can strengthen predatory effects on heterospecific prey and can have impacts on various, traits of both predator and prey. Because animals commonly broaden their diet as they grow, such negative impacts of predator cannibalism on the heterospecific prey may be common in interactions between predators and prey species of similar size. PMID- 26378312 TI - Beyond dichotomous life histories in partially migrating populations: cessation of anadromy in a long-lived fish. AB - Across animal taxa, migration allows individuals to exploit habitats and resources that predictably vary seasonally in suitability. Theory predicts that the "decision" to migrate or not is shaped by the relative fitness costs and benefits of exhibiting a given life history. Adoption of a migratory strategy is widely thought to reflect a dichotomous outcome; individuals are either resident or migratory, and continue to exhibit this life history until death. In fishes, anadromy and freshwater residency represents a well-studied life history dichotomy. Resident individuals may adopt a migratory life history later in life, but migratory individuals are not known to abandon this pattern. Here, we investigated the fitness benefits, as measured by body size, of residency and anadromy in a salmonid fish, Dolly Varden, Salvelinus malma, in Alaska, and reveal a novel life history: cessation of migration by older, larger individuals. Otolith microchemical analysis of Dolly Varden showed that while most fish migrated to sea at least once in their lives, lifelong resident fish exist in streams with close proximity to the ocean. Moreover, the probability of seaward migration in any year of life decreased annually after an individual's fourth year, and no fish migrated after their eighth year, while the oldest fish were captured in their 11th year. Migration conferred a size advantage in young fish, but the size benefits of marine foraging declined in older fish, at which time fish increasingly "retired from anadromy." Additionally, measurement of both natal otolith chemistry and the gonadosomatic index indicated a continued contribution to lifetime fitness, rather than senescence, in retired individuals. We suggest that the novel life history of reversion to residency by older fish is viable because foraging opportunities are subsidized by the predictable annual supply of energy-rich eggs and carcasses of spawning Pacific salmon. PMID- 26378313 TI - Invasive prey indirectly increase predation on their native competitors. AB - Ecological theory predicts that invasive prey can interact with native prey directly by competing for shared resources or indirectly by changing the abundance or behavior of shared native predators. However, both the study and management of invasive prey have historically overlooked indirect effects. In southern California estuaries, introduction of the Asian nest mussel Arcuatula senhousia has been linked to profound changes in native bivalve assemblages, but the mechanisms of these interactions remain unclear. We performed three field experiments to assess the mechanisms of competition between Arcuatula and native bivalves, and evaluated the potential for Arcuatula to indirectly mediate native predator-prey dynamics. We found that Arcuatula reduces the diversity, abundance, and size of native bivalve recruits by preemptively exploiting space in surface sediments. When paired with native shallow-dwelling clams (Chione undatella and Laevicardium substriatum), Arcuatula reduces adult survival through overgrowth competition. However, Arcuatula also attracts native predators, causing apparent competition by indirectly increasing predation of native clams, especially for poorly defended species. Therefore, invasive prey can indirectly increase predation rates on native competitors by changing the behavior of shared native predators, but the magnitude of apparent competition strongly depends on the vulnerability of natives to predation. Interestingly, our results indicate that the vulnerability of invasive prey to predation can greatly exacerbate impacts on their native competitors. Our findings suggest that consideration of both direct and indirect effects of invasive prey, as well as native predator-prey relationships, should lead to more effective invasive species management. PMID- 26378314 TI - Hunting alters seedling functional trait composition in a Neotropical forest. AB - Defaunation alters trophic interactions between plants and vertebrates, whichmay disrupt trophic cascades, thereby favoring a subset of plant species and reducing diversity. If particular functional traits characterize the favored plant species,.then defaunation may alter community-wide patterns of functional trait composition. Changes in plant functional traits occurring with defaunation may help identify the species interactions affected by defaunation and the potential for other cascading effects of defaunation. We tested the hypotheses that defaunation would (1) disrupt seed dispersal, thereby favoring species whose dispersal agents are not affected (e.g., small birds, bats, and abiotic agents), (2) reduce seed predation, thereby favoring larger-seeded species, and (3) reduce herbivory, thereby favoring species with lower leaf mass per area (LMA), leaf toughness, and wood density. We examined how these six traits responded to vertebrate defaunation caused by hunters or by experimental exclosures among more than-30 000 woody seedlings in a lowland tropical moist forest. Exclosures reduced terrestrial frugivores, granivores, and herbivores, while hunters also reduced volant and arboreal frugivores and granivores. The comparison of exclosures and hunting allowed us to parse the impacts of arboreal and volant species (reduced by hunters only) and terrestrial species (reduced by both hunters and exclosures). The loss of terrestrial vertebrates alone had limited effects on plant trait composition. The additional loss of volant and arboreal vertebrates caused significant shifts in plant species composition towards communities with more species dispersed abiotically, including lianas and low wood-density tree species, and fewer species dispersed by large vertebrates. In contrast to previous studies, community seed mass did not decline significantly in hunted sites. Our exclosure results suggest this is because reducing seed predators disproportionately benefits large-seeded species,.partially compensating for the reduction of seed dispersers at hunted sites. Our result9sdemonstrate that decreased seed dispersal and seed predation are important determinants of seedling community compositional change as a consequence of defaunation. Defaunation may also negatively impact carbon storage in tropical forests, by favoring lianas and low wood density tree species. PMID- 26378315 TI - Experimental reduction of winter food decreases body condition and delays migration in a long-distance migratory bird. AB - Many tropical habitats experience pronounced dry seasons, during which arthropod food availability declines, potentially limiting resident and migratory animal populations. In response to declines in food, individuals may attempt to alter their space use to enhance access to food resources, but may be socially constrained from doing so by con- and heterospecifics. If social constraints exist, food declines should result in decreased body condition. In migratory birds, correlational evidence suggests a link between body condition and migration timing. Poor body condition and delayed migration may, in turn, impact fitness in subsequent seasons via carry-over effects. To determine if winter food availability affects space use, inter- and intraspecific competition, body composition (i.e., mass, fat, and pectoral muscle), and migration timing, we experimentally decreased food availability on individual American Redstart (Setophaga ruticilla) territories in high-quality mangrove habitat. Redstarts on control territories experienced -40% loss of food due to the seasonal nature of the environment. Redstarts on experimental territories experienced -80% declines in food, which closely mimicked natural declines in nearby, low-quality, scrub habitat. Individuals on food-reduced territories did not expand their territories locally, but instead either became non-territorial "floaters" or remained on territory. Regardless of territorial status, food-reduced American Redstarts all deposited fat compared to control birds. Fat deposits provide insurance against the risk of starvation, but, for American Redstarts, came at the expense of maintaining pectoral muscle. Subsequently, food-reduced American Redstarts experienced, on average, a one-week delay in departure on spring migration, likely due to the loss of pectoral muscle. Thus, our results demonstrate experimentally, for the first time, that declines in winter food availability can result in a fat-muscle trade-off, which, in turn, delays departure on spring migration. Previous work has demonstrated that, for each day delayed after the first male arrival on the breeding grounds, American Redstarts experience an 11% decrease in the chance of successfully reproducing. Therefore, such delays in departure likely lead to fitness costs for migratory birds. Because tropical seasonal forests are expected to become drier in response to global climate change, Neotropical migratory bird populations may experience significant winter food limitation, further exacerbating population declines in the coming decades. PMID- 26378316 TI - Natural selection by pulsed predation: survival of the thickest. AB - Selective predation can lead to natural selection in prey populations and may alleviate competition among surviving individuals. The processes of selection and competition can have substantial effects on prey population dynamics, but are rarely studied simultaneously. Moreover, field studies of predator-induced short term selection pressures on prey populations are scarce. Here we report measurements of density dependence in body composition in a bivalve prey (edible cockle, Cerastoderma edule) during bouts of intense predation by an avian predator (Red Knot, Calidris canutus). We measured densities, patchiness, morphology, and body composition (shell and flesh mass) of cockles in a quasi experimental setting, i.e., before and after predation in three similar plots of 1 ha each, two of which experienced predation, and one of which remained unvisited in the course of the short study period and served as a reference. An individual's shell and flesh mass declined with cockle density (negative density dependence). Before predation, cockles were patchily distributed. After predation, during which densities were reduced by 78% (from 232 to 50 cockles/m2), the patchiness was substantially reduced, i.e., the spatial distribution was homogenized. Red Knots selected juvenile cockles with an average length of 6.9 +/- 1.0 mm (mean +/- SD). Cockles surviving predation had heavier shells than before predation (an increase of 21.5 percentage points), but similar flesh masses. By contrast, in the reference plot shell mass did not differ statistically between initial and final sampling occasions, while flesh mass was larger (an increase of 13.2 percentage points). In this field study, we show that Red Knots imposed a strong selection pressure on cockles to grow fast with thick shells and little flesh mass, with selection gradients among the highest reported in the literature. PMID- 26378317 TI - Drought sensitivity predicts habitat size sensitivity in an aquatic ecosystem. AB - Species and trophic richness often increase with habitat size. Although many ecological processes have been evoked to explain both patterns, the environmental stress associated with small habitats has rarely been considered. We propose that larger habitats may be species rich simply because their environmental conditions are within the fundamental niche of more species; larger habitats may also have more trophic levels if traits of predators render them vulnerable to environmental stress. We test this hypothesis using the aquatic insect larvae in water-filled bromeliads. In bromeliads, the probability of desiccation is greatest in small plants. For the 10 most common bromeliad insect taxa, we ask whether differences in drought tolerance and regional abundances between taxa predict community and trophic composition over a gradient of bromeliad size. First, we used bromeliad survey data to calculate the mean habitat size of occurrence of each taxon. Comparing the observed mean habitat size of occurrence to that expected from random species assembly based on differences in their regional abundances allowed us to obtain habitat size sensitivity indices (as Z scores) for the various insect taxa. Second, we obtained drought sensitivity indices by subjecting individual insects to drought and measuring the effects on relative growth rates in a mesocosm experiment. We found that drought sensitivity strongly, predicts habitat size sensitivity in bromeliad insects. However, an increase in trophic richness with habitat size could not be explained by an increased sensitivity of predators to drought, but rather by sampling effects, as predators were rare compared to lower trophic levels. This finding suggests that physiological tolerance to environmental stress can be relevant in explaining the universal increase in species with habitat size. PMID- 26378318 TI - Female butterflies adapt and allocate their progeny to the host-plant quality of their own larval experience. AB - Recent studies with diverse taxa have shown that parents can utilize their experience of the environment to adapt their offspring's phenotype to the same environmental conditions. Thus, offspring would then perform best under environmental conditions experienced by their parents due to transgenerational phenotypic plasticity. Such an effect has been dubbed transgenerational acclimatization. However, evidence that parents can subsequently ensure the appropriate environmental conditions in order that offspring benefit from transgenerational acclimatization has never been demonstrated. We reared Pieris rapae larvae in the parental generation on high-nitrogen and low-nitrogen host plants, and reared the offspring (F1) of both treatments again on high- and low nitrogen plants. Furthermore, we tested if females prefer to oviposit on high- or low-nitrogen host plants in two-way choice tests. We here show not only that females adapt their offspring's phenotype to the host-plant quality that they themselves experienced, but that females also mainly oviposit on the host quality to which they adapt their offspring. Moreover, effects of larval host plant on oviposition preference of females increased across two generations in F1-females acclimatized to low-nitrogen host plants, showing an adaptive host shift from one generation to the next. These findings may have profound implications for host race formation and sympatric speciation. PMID- 26378319 TI - Genetics-based interactions among plants, pathogens, and herbivores define arthropod community structure. AB - Plant resistance to pathogens or insect herbivores is common, but its potential for indirectly influencing plant-associated communities is poorly known. Here, we test whether pathogens' indirect effects on arthropod communities and herbivory depend on plant resistance to pathogens and/or herbivores, and address the overarching interacting foundation species hypothesis that genetics-based interactions among a few highly interactive species can structure a much larger community. In a manipulative field experiment using replicated genotypes of two Populus species and their interspecific hybrids, we found that genetic variation in plant resistance to both pathogens and insect herbivores modulated the strength of pathogens' indirect effects on arthropod communities and insect herbivory. First, due in part to the pathogens' differential impacts on leaf biomass among the two Populus species and the hybrids, the pathogen most strongly impacted arthropod community composition, richness, and abundance on the pathogen susceptible tree species. Second, we found similar patterns comparing pathogen susceptible and pathogen-resistant genotypes within species. Third, within a plant species, pathogens caused a fivefold greater reduction in herbivory on insect-herbivore-susceptible plant genotypes than on herbivore-resistant genotypes, demonstrating that the pathogen-herbivore interaction is genotype dependent. We conclude that interactions among plants, pathogens, and herbivores can structure multitrophic communities, supporting the interacting foundation species hypothesis. Because these interactions are genetically based, evolutionary changes in genetic resistance could result in ecological changes in associated communities, which may in turn feed back to affect plant fitness. PMID- 26378320 TI - Microbial functional diversity enhances predictive models linking environmental parameters to ecosystem properties. AB - Microorganisms drive biogeochemical processes, but linking these processes to real changes in microbial communities under field conditions is not trivial. Here, we present a model-based approach to estimate independent contributions of microbial community shifts to ecosystem properties. The approach was tested empirically, using denitrification potential as our model process, in a spatial survey of arable land encompassing a range of edaphic conditions and two agricultural production systems. Soil nitrate was the most important single predictor of denitrification potential (the change in Akaike's information criterion, corrected for sample size, DeltaAIC(c) = 20.29); however, the inclusion of biotic variables (particularly the evenness and size of denitrifier communities [DeltaAIC(c) = 12.02], and the abundance of one denitrifier genotype [DeltaAIC(c) = 18.04]) had a substantial effect on model precision, comparable to the inclusion of abiotic variables (biotic R2 = 0.28, abiotic R2 = 0.50, biotic + abiotic R2 = 0.76). This approach provides a valuable tool for explicitly linking microbial communities to ecosystem functioning. By making this link, we have demonstrated that including aspects of microbial community structure and diversity in biogeochemical models can improve predictions of nutrient cycling in ecosystems and enhance our understanding of ecosystem functionality. PMID- 26378321 TI - Ultraviolet photodegradation facilitates microbial litter decomposition in a Mediterranean climate. AB - Rates of litter decomposition in dryland ecosystems are consistently underestimated by decomposition models driven by temperature, moisture, and litter chemistry. The most common explanation for this pattern is that ultraviolet radiation (UV) increases decomposition through photodegradation of the litter lignin fraction. Alternatively, UV could increase decomposition through effects on microbial activity. To assess the mechanisms underlying UV photodegradation in a semiarid climate, we exposed high- and low-lignin litter to ambient and blocked UV over 15 months in a Mediterranean ecosystem. We hypothesized that UV would increase litter mass loss, that UV would preferentially increase mass loss of the lignin fraction, and that UV would have a negative effect on microbial activity. Consistent with our first hypothesis, we found that UV-blocking reduced litter mass loss from 16% to 1% in high-lignin litter and from 29% to 17% in low-lignin litter. Contrary to our second hypothesis, UV treatment did not have a significant effect on lignin content in either litter type. Instead, UV-blocking significantly reduced cellulose and hemicellulose mass loss in both litter types. Contrary to our third hypothesis, we observed a positive effect of UV on both fungal abundance and the potential activities of several assayed extracellular enzymes. Additionally, under ambient UV only, we found significant correlations between potential activities of cellulase and oxidase enzymes and both the concentrations and degradation rates of their target compounds. Our results indicate that UV is a significant driver of litter mass loss in Mediterranean ecosystems, but not solely because UV directly degrades carbon compounds such as lignin. Rather, UV facilitates microbial degradation of litter compounds, such as cellulose and hemicellulose. Thus, unexpectedly high rates of litter decomposition previously attributed directly to UV in dryland ecosystems may actually derive from a synergistic interaction between UV and microbes. PMID- 26378322 TI - Variability among individuals is generated at the gene expression level. AB - Selection acts on individuals, specifically on their differences. To understand adaptation and responses to change therefore requires knowledge of how variation is generated and distributed across traits. Variation occurs on different biological scales, from genetic through physiological to morphological, yet it is unclear which of these carries the most variability. For example, if individual variation is mainly generated by differences in gene expression, variability should decrease progressively from coding genes to morphological traits, whereas if post-translational and epigenetic effects increase variation, the opposite should occur. To test these predictions, we compared levels of variation among individuals in various measures of gene expression, physiology (including activity), and morphology in two abundant and geographically widespread Antarctic molluscs, the clam Laternula elliptica and the limpet Nacella concinna. Direct comparisons among traits as diverse as heat shock protein QPCR assays, whole transcription profiles, respiration rates, burying rate, shell length, and ash free dry mass were made possible through the novel application of an established metric, the Wentworth Scale. In principle, this approach could be extended to analyses of populations, communities, or even entire ecosystems. We found consistently greater variation in gene expression than morphology, with physiological measures falling in between. This suggests that variability is generated at the gene expression level. These findings have important implications for refining current biological models and predictions of how biodiversity may respond to climate change. PMID- 26378323 TI - High potential for iron reduction in upland soils. AB - Changes in the redox state of iron (Fe) can be coupled to the biogeochemical cycling of carbon (C), nitrogen, and phosphorus, and thus regulate soil C, ecosystem nutrient availability, and greenhouse gas production. However, its importance broadly in non-flooded upland terrestrial ecosystems is unknown. We measured Fe reduction in soil samples from an annual grassland, a drained peatland, and a humid tropical forest We incubated soil slurries in an anoxic glovebox for 5.5 days and added sodium acetate daily at rates up to 0.4 mg C x (g soil)(-1) x d(-1). Soil moisture, poorly crystalline Fe oxide concentrations, and Fe(II) concentrations differed among study sites in the following order: annual grassland < drained peatland < tropical forest (P < 0.001 for all characteristics). All of the soil samples demonstrated high Fe reduction potential with maximum rates over the course of the incubation averaging 1706 +/- 66, 2016 +/- 12, and 2973 +/- 115 MUg Fe x (g soil)(-1) x d(-1) (mean +/- SE) for the tropical forest, annual grassland, and drained peatland, respectively. Our results suggest that upland soils from diverse ecosystems have the potential to exhibit high short-term rates of Fe reduction that may play an important role in driving soil biogeochemical processes during periods of anaerobiosis. PMID- 26378324 TI - Rethinking the linear regression model for spatial ecological data: comment. PMID- 26378325 TI - Rethinking the linear regression model for spatial ecological data: reply. PMID- 26378326 TI - River dolphins can act as population trend indicators in degraded freshwater systems: comment. PMID- 26378338 TI - Effect of adduct formation with molecular nitrogen on the measured collisional cross sections of transition metal-1,10-phenanthroline complexes in traveling wave ion-mobility spectrometry: N2 is not always an "inert" buffer gas. AB - The number of separations and analyses of molecular species using traveling wave ion-mobility spectrometry-mass spectrometry (TWIMS-MS) is increasing, including those extending the technique to analytes containing metal atoms. A critical aspect of such applications of TWIMS-MS is the validity of the collisional cross sections (CCSs) measured and whether they can be accurately calibrated against other ion-mobility spectrometry (IMS) techniques. Many metal containing species have potential reactivity toward molecular nitrogen, which is present in high concentration in the typical Synapt-G2 TWIMS cell. Here, we analyze the effect of nitrogen on the drift time of a series of cationic 1,10-phenanthroline complexes of the late transition metals, [(phen)M](+), (M = Ni, Pd, Pt, Cu, Ag, Au, Zn, Cd, and Hg) in order to understand potential deviations from expected drift time behaviors. These metal complexes were chosen for their metal open-coordination site and lack of rotameric species. The target species were generated via electrospray ionization (ESI), analyzed using TWIMS in N2 drift gas, and the observed drift time trends compared. Theoretically derived CCSs for all species (via both the projection approximation and trajectory method) were also compared. The results show that, indeed, for metal containing species in this size regime, reaction with molecular nitrogen has a dramatic effect on measured drift times and must not be ignored when comparing and interpreting TWIMS arrival time distributions. Density-functional theory (DFT) calculations are employed to analyze the periodic differences due to the metal's interaction with nitrogen (and background water) in detail. PMID- 26378340 TI - NH3 Binding to the S2 State of the O2-Evolving Complex of Photosystem II: Analogue to H2O Binding during the S2 -> S3 Transition. AB - Ammonia binds directly to the oxygen-evolving complex of photosystem II (PSII) upon formation of the S2 intermediate, as evidenced by electron paramagnetic resonance spectroscopy. We explore the binding mode by using quantum mechanics/molecular mechanics methods and simulations of extended X-ray absorption fine structure spectra. We find that NH3 binds as an additional terminal ligand to the dangling Mn4, instead of exchanging with terminal water. Because water and ammonia are electronic and structural analogues, these findings suggest that water binds analogously during the S2 -> S3 transition, leading to rearrangement of ligands in a carrousel around Mn4. PMID- 26378341 TI - Facebook or Memory: Which Is the Real Threat to Your Relationship? AB - This study examined the role of Facebook friends lists in identifying potential sexual and committed relationship alternatives and the effects this had on relationship investment in a sample of 371 young adult undergraduates. A Facebook versus memory experimental protocol was developed to test whether Facebook friends lists act as primers for recognition of potential sexual and committed relationship partners and whether identifying these potential partners (either from Facebook or from memory) caused lower relationship investment. Facebook friends lists did act as memory primers for potential partners, but only for sexual partners, and the effect was stronger for men than it was for women. However, identifying potential partners through Facebook actually lowered a person's perceptions of the quality of their alternatives. In contrast, merely thinking about potential alternatives from one's social sphere lowered relationship satisfaction and commitment with one's current committed partner. The implications of these findings are discussed in relation to current work on the negative effects of Facebook use on relationship outcomes. PMID- 26378339 TI - Methods for identification and confirmation of targeted subgroups in clinical trials: A systematic review. AB - Important objectives in the development of stratified medicines include the identification and confirmation of subgroups of patients with a beneficial treatment effect and a positive benefit-risk balance. We report the results of a literature review on methodological approaches to the design and analysis of clinical trials investigating a potential heterogeneity of treatment effects across subgroups. The identified approaches are classified based on certain characteristics of the proposed trial designs and analysis methods. We distinguish between exploratory and confirmatory subgroup analysis, frequentist, Bayesian and decision-theoretic approaches and, last, fixed-sample, group sequential, and adaptive designs and illustrate the available trial designs and analysis strategies with published case studies. PMID- 26378342 TI - Correlations of Gut Microbial Community Shift with Hepatic Damage and Growth Inhibition of Carassius auratus Induced by Pentachlorophenol Exposure. AB - Goldfish (Carassius auratus) were exposed to 0-100 MUg/L pentachlorophenol (PCP) for 28 days to investigate the correlations of fish gut microbial community shift with the induced toxicological effects. PCP exposure caused accumulation of PCP in the fish intestinal tract in a time- and dose-dependent manner, while hepatic PCP reached the maximal level after a 21 day exposure. Under the relatively higher PCP stress, the fish body weight and liver weight were reduced and hepatic CAT and SOD activities were inhibited, demonstrating negative correlations with the PCP levels in liver and gut content (R < -0.5 and P < 0.05 each). Pyrosequencing of the 16S rRNA gene indicated that PCP exposure increased the abundance of Bacteroidetes in the fish gut. Within the Bacteroidetes phylum, the Bacteroides genus had the highest abundance, which was significantly correlated with PCP exposure dosage and duration (R > 0.5 and P < 0.05 each). Bioinformatic analysis revealed that Bacteroides showed quantitatively negative correlations with Chryseobacterium, Microbacterium, Arthrobacter, and Legionella in the fish gut, and the Bacteroidetes abundance, Bacteroides abundance, and Firmicutes/Bacteroidetes ratio played crucial roles in the reduction of body weight and liver weight under PCP stress. The results may extend our knowledge regarding the roles of gut microbiota in ecotoxicology. PMID- 26378343 TI - Redox-Triggered alpha-C-H Functionalization of Pyrrolidines: Synthesis of Unsymmetrically 2,5-Disubstituted Pyrrolidines. AB - By using o-benzoquinone as an internal oxidant, the regio- and diastereoselective functionalization of the secondary over the tertiary alpha-C-H bond of 2 substituted pyrrolidines is first realized. Subsequent intermolecular addition of a nucleophile to the generated N,O-acetal and cleavage of the aromatic substituent leads to 2,5-disubstituted pyrrolidines. PMID- 26378344 TI - Comment on "Zirconium-Carbon Hybrid Sorbent for Removal of Fluoride from Water: Oxalic Acid Mediated Zr(IV) Assembly and Adsorption Mechanism". PMID- 26378345 TI - Free-Standing Optically Switchable Chiral Plasmonic Photonic Crystal Based on Self-Assembled Cellulose Nanorods and Gold Nanoparticles. AB - Photonic crystals incorporating with plasmonic nanoparticles have recently attracted considerable attention due to their novel optical properties and potential applications in future subwavelength optics, biosensing and data storage device. Here we demonstrate a free-standing chiral plasmonic film composed of entropy-driven self-co-assembly of gold nanoparticles (GNPs) and rod like cellulose nanocrystals (CNCs). The CNCs-GNPs composite films not only preserve the photonic ordering of the CNCs matrix but also retain the plasmonic resonance of GNPs, leading to a distinct plasmon-induced chiroptical activity and a strong resonant plasmonic-photonic coupling that is confirmed by the stationary and ultrafast transient optical response. Switchable optical activity can be obtained by either varying the incidence angle of lights, or by taking advantage of the responsive feature of the CNCs matrix. Notably, an angle-dependent plasmon resonance in chiral nematic hybrid film has been observed for the first time, which differs drastically from that of the GNPs embed in three-dimensional photonic crystals, revealing a close relation with the structure of the host matrix. The current approach for fabricating device-scale, macroscopic chiral plasmonic materials from abundant CNCs with robust chiral nematic matrix may enable the mass production of functional optical metamaterials. PMID- 26378347 TI - The Aging of the Global Population: The Changing Epidemiology of Disease and Spinal Disorders. AB - The global population is currently undergoing an upward shift in its age structure due to decreasing fertility rates and increasing life expectancy. As a result, clinicians worldwide will be required to manage an increasing number of spinal disorders specific to the elderly and the aging of the spine. Elderly individuals pose unique challenges to health care systems and to spinal physicians as these patients typically have an increased number of medical comorbidities, reduced bone density mass, more severe spinal degeneration and a greater propensity to falls. In anticipation of the aging of the population, we undertook this project to heighten physicians' awareness of age-related spinal disorders, including geriatric odontoid fractures, central cord syndrome, osteoporotic compression fractures, degenerative cervical myelopathy, lumbar spinal stenosis and degenerative spinal deformity. This introductory article provides an overview of the changing demographics of the global population; discusses the age-related alterations that may occur to the spine; and summarizes the purpose and contents of this focus issue. PMID- 26378348 TI - Minimally Invasive Spinal Surgery in the Elderly: Does It Make Sense? AB - Lumbar degenerative disease can have varied pathoanatomy, with stenosis, spondylolisthesis, and scoliosis contributing to significant pain and disability. Among appropriately selected patients, surgical intervention can treat both back pain and leg pain and improve quality of life in a cost-effective manner with an acceptable safety profile. The evolution of minimally invasive surgical (MIS) techniques offers the potential to decrease the physiological impact of surgery and to improve the complication profile while achieving the same spine surgical objectives. The utility of such techniques among elderly patients >65 years of age has not been rigorously evaluated, and this systematic review sought to define the utility and safety of MIS spinal surgery for decompression, interbody fusion, and deformity correction in this population. Review of 2 studies for MIS lumbar decompression reveals that the majority of elderly patients exhibit significant improvements in pain (change in visual analog score for leg pain, 3.4 points) and disability (change in Oswestry Disability Index, 19 points), with inadvertent durotomy in 3% of patients. Review of 4 studies for MIS lumbar interbody fusion reveals robust improvement in pain (change in visual analog score for leg pain, 3.4 points; change in visual analog score for back pain, 7.2 points), with inadvertent durotomy in 5% of patients. Narrative review was performed for adult degenerative deformity correction, revealing that MIS techniques are feasible for managing such patients with acceptable rates of osseous union and complication. On the basis of largely low-quality, retrospective evidence, we recommend that elderly patients should not be excluded from MIS interventions for symptomatic lumbar degenerative spinal disease. PMID- 26378349 TI - A Cost-Utility Analysis of Lumbar Decompression With and Without Fusion for Degenerative Spine Disease in the Elderly. AB - BACKGROUND: Value-based purchasing is rapidly being implemented to rein in the unsustainably rising costs of the US healthcare system. With a growing elderly population, it is vital to understand the value of spinal surgery in this group of individuals. OBJECTIVE: To compare the cost-effectiveness of lumbar decompression with and without fusion for degenerative spine disease in elderly vs nonelderly patients. METHODS: A total of 221 patients undergoing elective primary surgery for degenerative lumbar pathology who were enrolled in a prospective longitudinal registry were analyzed. Patient-reported outcomes of Oswestry Disability Index, numeric rating scale for back and leg pain, and quality-of-life scores (EuroQol-5D) were recorded. Two-year back-related medical resource use, missed work, and health-state values (quality-adjusted life-years [QALYs]) were assessed. Two-year resource use was multiplied by unit costs based on Medicare national allowable payment amounts (direct cost). Patient and caregiver workday losses were multiplied by gross-of-tax wage rate (indirect cost). Patients were divided into age groups <70 and >=70 years. RESULTS: Mean cumulative 2-year QALYs gained were statistically similar between younger and older patients for both decompression alone (0.67 +/- 0.65 vs 0.56 +/- 0.65; P = .47) and decompression with fusion (0.56 +/- 0.55 vs 0.59 +/- 0.55; P = .26). Mean 2-year cost per QALY gained between younger and older patients was similar for both decompression alone ($24,365 vs $31,750 per QALY; P = .11) and decompression with fusion ($64,228 vs $60,183 per QALY; P = .09). CONCLUSION: Surgical treatment provided significant improvements in pain, disability, and quality of life for elderly patients with degenerative lumbar disease. Observed costs per QALY gained for lumbar decompression with and without fusion were similar for younger and older patients, demonstrating that lumbar spine surgery in the elderly is an equally cost-effective and valuable intervention. PMID- 26378350 TI - Lumbar Surgery in the Elderly Provides Significant Health Benefit in the US Health Care System: Patient-Reported Outcomes in 4370 Patients From the N2QOD Registry. AB - BACKGROUND: Lumbar spine degenerative pathologies are prevalent in the United States. The health benefit of spine surgery in the elderly has been questioned. OBJECTIVE: To compare effectiveness, morbidity, and quality of care associated with surgical management of degenerative lumbar spinal disorders in elderly vs nonelderly patients. METHODS: The National Neurosurgery Quality and Outcomes Database registry prospectively collects measures of surgical safety and patient reported outcomes for 1 year after surgery. All lumbar surgery cases were queried to compare the elderly surgical population (70 years of age and older) and associated outcomes with patients younger than 70 years of age. RESULTS: A total of 4370 lumbar spine surgeries were enrolled in National Neurosurgery Quality and Outcomes Database with 1-year follow-up; 1020 (23%) were elderly patients. The elderly had an increased incidence of heart disease, osteoporosis, high-risk anesthesia grade (American Society of Anesthesiologists grade 3/4), more than 3 level surgery, ambulation assist device use, unemployment, female sex, white race, and stenosis as a diagnosis. The elderly patients had a lower body mass index, incidence of anxiety/depression, liability/workers' compensation claims, and disc herniation as a diagnosis. Length of hospitalization and postdischarge inpatient rehabilitation/nursing facility was significantly greater in the elderly. The incidence of surgical complications and 90-day hospital readmission were similar. Significant and equivalent improvements at 1 year in pain, disability, and quality of life were reported by both elderly and nonelderly patients overall and for each unique spine diagnosis. CONCLUSION: For all ages, lumbar spine surgery resulted in significant improvement in pain, disability, and quality of life. Elderly patients experienced equivalent and significant health benefit in all measured health domains without an increased rate of surgical complications or hospital readmissions. Elective lumbar spine surgery in the elderly provides significant gains in health status, justifying its continued use in this growing population. PMID- 26378351 TI - Trends for Spine Surgery for the Elderly: Implications for Access to Healthcare in North America. AB - The proportion of the population over age 65 in the United States continues to increase over time, from 12% in 2000 to a projected 20% by 2030. There is an associated rise in the prevalence of degenerative spinal disorders with this aging population. This will lead to an increase in demand for both nonsurgical and surgical treatment for these disabling conditions, which will stress an already overburdened healthcare system. Utilization of spinal procedures and services has grown considerably. Comparing 1999 to 2009, lumbar epidural steroid injections have increased by nearly 900,000 procedures performed per year, while physical therapy evaluations have increased by nearly 1.4 million visits per year. We review the literature regarding the cost-effectiveness of spinal surgery compared to conservative treatment. Decompressive lumbar spinal surgery has been shown to be cost-effective in several studies, while adult spinal deformity surgery has higher total cost per quality-adjusted life year gained in the short term. With an aging population and unsustainable healthcare costs, we may be faced with a shortfall of beneficial spine care as demand for spinal surgery in our elderly population continues to rise. ABBREVIATION: QALY, quality-adjusted life year. PMID- 26378352 TI - Appropriate Use of Limited Interventions vs Extensive Surgery in the Elderly Patient With Spinal Disorders. AB - Surgical management of spinal deformity is elderly patients is characterized by significant variability. In a value-based health care economy, minimization of risks and maximization of benefit and durability of surgery are a priority. The choice of a surgical approach is a significant determinant of risk, cost, and outcome. Informed choice regarding a surgical approach requires participation of the patient and surgeon. Limited interventions may be appropriate for patients with radicular symptoms and focal pain. More extensive surgery may be required for patients with global imbalance of the spine. The role of minimally invasive approaches in limiting complications and improving outcome remains in evolution. An optimal choice of surgical approach requires consideration of patient preferences, values, comorbidities, and goals of care. PMID- 26378353 TI - Optimal Timing of Surgical Decompression for Acute Traumatic Central Cord Syndrome: A Systematic Review of the Literature. AB - BACKGROUND: Traumatic central cord syndrome (TCCS) is an incomplete spinal cord injury defined by greater weakness in upper versus lower extremities, variable sensory loss, and variable bladder, bowel, and sexual dysfunction. The optimal timing of surgery for TCCS remains controversial. OBJECTIVE: To determine whether timing of surgery for TCCS predicts neurological outcomes, length of stay, and complications. METHODS: Five databases were searched through March 2015. Articles were appraised independently by 2 reviewers, and the evidence synthesized according to Grading of Recommendation Assessment, Development and Evaluation principles. RESULTS: Nine studies (3 prognostic, 5 therapeutic, 1 both) satisfied inclusion criteria. Low level evidence suggests that patients operated on <24 hours after injury exhibit significantly greater improvements in postoperative American Spinal Injury Association motor scores and the functional independence measure at 1 year than those operated on >24 hours after injury. Moderate evidence suggests that patients operated on <2 weeks after injury have a higher postoperative Japanese Orthopaedic Association score and recovery rate than those operated on >2 weeks after injury. There is insufficient evidence that lengths of hospital or intensive care unit stay differ between patients who undergo early versus delayed surgery. Furthermore, there is insufficient evidence that timing between injury and surgery predicts mortality rates or serious or minor adverse events. CONCLUSION: Surgery for TCCS <24 hours after injury appears safe and effective. Although there is insufficient evidence to provide a clear recommendation for early surgery (<24 hours), it is preferable to operate during the first hospital admission and <2 weeks after injury. PMID- 26378354 TI - Progressive Spinal Kyphosis in the Aging Population. AB - Thoracic kyphosis tends to increase with age. Hyperkyphosis is defined as excessive curvature of the thoracic spine and may be associated with adverse health effects. Hyperkyphosis in isolation or as a component of degenerative kyphoscoliosis has important implications for the surgical management of adult spinal deformity. Our objective was to review the literature on the epidemiology, etiology, natural history, management, and outcomes of thoracic hyperkyphosis. We performed a narrative review of literature on thoracic hyperkyphosis and its implications for adult spinal deformity surgery. Hyperkyphosis has a prevalence of 20% to 40% and is more common in the geriatric population. The cause is multifactorial and involves an interaction between degenerative changes, vertebral compression fractures, muscular weakness, and altered biomechanics. It may be associated with adverse health consequences including impaired physical function, pain and disability, impaired pulmonary function, and increased mortality. Nonoperative management may slow the progression of kyphosis and improve function. Surgery is rarely performed for isolated hyperkyphosis in the elderly due to the associated risk, but is an option when kyphosis occurs in the context of significant deformity. In this scenario, increased thoracic kyphosis influences selection of fusion levels and overall surgical planning. Kyphosis is common in older individuals and is associated with adverse health effects and increased mortality. Current evidence suggests a role for nonoperative therapies in reducing kyphosis and delaying its progression. Isolated hyperkyphosis in the elderly is rarely treated surgically; however, increased thoracic kyphosis as a component of global spinal deformity has important implications for patient selection and operative planning. PMID- 26378355 TI - Impact of Movement Disorders on Management of Spinal Deformity in the Elderly. AB - Spinal deformities are frequent and disabling complications of movement disorders such as Parkinson disease and multiple system atrophy. The most distinct spinal deformities include camptocormia, antecollis, Pisa syndrome, and scoliosis. Spinal surgery has become lower risk and more efficacious for complex spinal deformities, and thus more appealing to patients, particularly those for whom conservative treatment is inappropriate or ineffective. Recent innovations and advances in spinal surgery have revolutionized the management of spinal deformities in elderly patients. However, spinal deformity surgeries in patients with Parkinson disease remain challenging. High rates of mechanical complications can necessitate revision surgery. The success of spinal surgery in patients with Parkinson disease depends on an interdisciplinary approach, including both surgeons and movement disorder specialists, to select appropriate surgical patients and manage postoperative movement in order to decrease mechanical failures. Achieving appropriate correction of sagittal alignment with strong biomechanical instrumentation and bone fusion is the key determinant of satisfactory results. PMID- 26378356 TI - Management of the Elderly With Vertebral Compression Fractures. AB - Vertebral compression fractures (VCFs) are the most common type of fracture secondary to osteoporosis. These fractures are associated with significant rates of morbidity and mortality and annual direct medical expenditures of more than $1 billion in the United States. Although many patients will respond favorably to nonsurgical care of their VCF, contemporary natural history data suggest that more than 40% of patients may fail to achieve significant pain relief within 12 months of symptom onset. As a result, percutaneous vertebral augmentation is often used to hasten symptom resolution and return of function. However, controversy regarding the role of kyphoplasty and vertebroplasty in the treatment of symptomatic VCFs exists. The purposes of this review are (1) to outline the epidemiology of VCFs as well as the physical morbidity and economic impact of these injuries, (2) to familiarize the reader with the best available evidence surrounding the operative and nonoperative treatment of VCFs, and (3) to examine the literature pertaining to the cost-effectiveness of surgical management of VCFs with the overarching goal of helping physicians make informed decisions regarding symptomatic VCF treatment. PMID- 26378357 TI - The Burden of Spinal Disorders in the Elderly. AB - Disorders of the spine are common and have a significant and measurable burden on affected patients and on our healthcare economy. The burden of spinal disorders encompasses metrics such as the prevalence of spinal disorders, the impact of spinal disorders on health-related quality of life, and the use of resources associated with the operative and nonoperative management of spinal disorders. Measurement of the burden of spinal disorders is important in prioritizing the distribution of limited resources within our healthcare economy. In 1998, the Priority Setting Committee of the Institute of Medicine concluded that in defining health priorities for research and funding, the burden of disease and impact on the health of the population should be the primary determinants of resource allocation. The purpose of this article is to report metrics comprising the burden of spinal disorders, with a focus on the significant and growing burden of spinal disorders in our elderly population, and to demonstrate that allocation of resources to the management of spinal disorders should be a priority for our healthcare economy. PMID- 26378358 TI - Degenerative Cervical Myelopathy: A Spectrum of Related Disorders Affecting the Aging Spine. AB - Cervical spinal cord dysfunction can result from either traumatic or nontraumatic causes, including tumors, infections, and degenerative changes. In this article, we review the range of degenerative spinal disorders resulting in progressive cervical spinal cord compression and propose the adoption of a new term, degenerative cervical myelopathy (DCM). DCM comprises both osteoarthritic changes to the spine, including spondylosis, disk herniation, and facet arthropathy (collectively referred to as cervical spondylotic myelopathy), and ligamentous aberrations such as ossification of the posterior longitudinal ligament and hypertrophy of the ligamentum flavum. This review summarizes current knowledge of the pathophysiology of DCM and describes the cascade of events that occur after compression of the spinal cord, including ischemia, destruction of the blood spinal cord barrier, demyelination, and neuronal apoptosis. Important features of the diagnosis of DCM are discussed in detail, and relevant clinical and imaging findings are highlighted. Furthermore, this review outlines valuable assessment tools for evaluating functional status and quality of life in these patients and summarizes the advantages and disadvantages of each. Other topics of this review include epidemiology, the prevalence of degenerative changes in the asymptomatic population, the natural history and rates of progression, risk factors of diagnosis (clinical, imaging and genetic), and management strategies. PMID- 26378359 TI - A Systematic Review of the Treatment of Geriatric Type II Odontoid Fractures. AB - BACKGROUND: Odontoid fractures are the most common cervical spine fracture in the geriatric population; however, the treatment of type II odontoid fractures in this age group is controversial. OBJECTIVE: To compare the short-term (<3 months) mortality, long-term (>=12 months) mortality, and complication rates of patients >60 years of age with a type II odontoid fracture managed either operatively or nonoperatively. METHODS: We performed a systematic review of literature published between January 1, 2000, and February 1, 2015, related to the treatment of type II odontoid fractures in patients >60 years of age. An analysis of short-term mortality, long-term mortality, and the occurrence of complications was performed. RESULTS: A total of 452 articles were identified, of which 21 articles with 1233 patients met the inclusion criteria. Short-term mortality (odds ratio, 0.43; 95% confidence interval, 0.30-0.63) and long-term mortality (odds ratio, 0.47; 95% confidence interval, 0.34-0.64) were lower in patients who underwent surgical treatment than in those who had nonsurgical treatment, and there were no significant differences in the rate of complications (odds ratio, 1.01; 95% confidence interval, 0.63-1.63). Surgical approach (posterior vs anterior) showed no significant difference in mortality or complication rate. Similarly, no difference in mortality or complication rate was identified with hard collar or a halo orthosis immobilization. CONCLUSION: The current literature suggests that well-selected patients >60 years of age undergoing surgical treatment for a type II odontoid fracture have a decreased risk of short-term and long-term mortality without an increase in the risk of complications. PMID- 26378360 TI - Management of Degenerative Lumbar Spinal Stenosis in the Elderly. AB - BACKGROUND: Lumbar spinal stenosis can cause symptomatic neurogenic claudication alongside radicular pain and weakness. In appropriately selected patients, surgical intervention has been demonstrated to provide for improvement in pain, disability, and quality of life. This systematic review sought to define the utility and safety of such decompression with or without arthrodesis in the management of symptomatic lumbar spinal stenosis for elderly patients older than 65 years of age. METHODS: A systematic review was conducted using MEDLINE for literature published through December 2014. The first question focused on the effectiveness of lumbar spinal surgery for symptomatic lumbar spinal stenosis in elderly patients (over age 65 y). The second question focused on safety of surgical intervention on this elderly population with emphasis on perioperative complication rates. RESULTS: Review of 11 studies reveals that the majority of elderly patients exhibit significant symptomatic improvement, with overall benefits observed for pain (change visual analog scale 4.4 points) and disability (change Oswestry Disability Index 23 points). Review of 11 studies reveals that perioperative complications were infrequent and acceptable with pooled estimates of mortality (0.5%), inadvertent durotomy (5%), and wound infection (2%). Outcomes seem less favorable with greater complication rates among patients with diabetes or obesity. CONCLUSION: Based on largely low-quality, retrospective evidence, we recommend that elderly patients should not be excluded from surgical intervention for symptomatic lumbar spinal stenosis. PMID- 26378361 TI - Degenerative Spinal Deformity. AB - Degenerative spinal deformity afflicts a significant portion of the elderly and is increasing in prevalence. Recent evidence has revealed sagittal plane malalignment to be a key driver of pain and disability in this population and has led to a significant shift toward a more evidence-based management paradigm. In this narrative review, we review the recent literature on the epidemiology, evaluation, management, and outcomes of degenerative adult spinal deformity (ASD). ASD is increasing in prevalence in North America due to an aging population and demographic shifts. It results from cumulative degenerative changes focused in the intervertebral discs and facet joints that occur asymmetrically to produce deformity. Deformity correction focuses on restoration of global alignment, especially in the sagittal plane, and decompression of the neural elements. General realignment goals have been established, including sagittal vertical axis <50 mm, pelvic tilt <22 degrees , and lumbopelvic mismatch <+/-9 degrees ; however, these should be tailored to the patient. Operative management, in carefully selected patients, yields satisfactory outcomes that appear to be superior to nonoperative strategies. ASD is characterized by malalignment in the sagittal and/or coronal plane and, in adults, presents with pain and disability. Nonoperative management is recommended for patients with mild, nonprogressive symptoms; however, evidence of its efficacy is limited. Surgery aims to restore global spinal alignment, decompress neural elements, and achieve fusion with minimal complications. The surgical approach should balance the desired correction with the increased risk of more aggressive maneuvers. In well-selected patients, surgery yields excellent outcomes. PMID- 26378362 TI - Perioperative Medical Management of Spine Surgery Patients With Osteoporosis. AB - Management of spine surgery patients with osteoporosis is challenging because of the difficulty of instrumenting and the potential complications, including nonunion and adjacent level fractures. Treatment of this patient population should involve a multidisciplinary approach including the spine surgeon, primary care physician, endocrinologist, and physical therapist. Indication for preoperative treatment before spinal fusion surgery is unclear. All patients should receive calcium and vitamin D. Hormone replacement therapy, including estrogen or selective estrogen receptor modulators, should be considered for elderly female patients with decreased bone mass. Bisphosphonates or intermittent parathyroid hormone are reserved for those with significant bone loss in the spine. Pretreatment with antiresorption medications affect bone remodeling, which is a vital part of graft incorporation and fusion. Although there have been numerous animal studies, there is limited clinical evidence. Accordingly, surgery should be delayed, if possible, to treat the osteoporosis before the intervention. Treatment may include bisphosphonates, as well as newer agents, such as recombinant parathyroid hormone. Further clinical data are needed to understand the relative advantages/disadvantage of antiresorptive vs anabolic agents, as well as the impact of administration of these medications before vs after fusion surgery. Future clinical studies will enable better understanding of the impact of current therapies on biomechanics and fusion outcomes in this unique and increasingly prevalent patient population. PMID- 26378363 TI - Surgical Management of Spinal Conditions in the Elderly Osteoporotic Spine. AB - Osteoporosis, the most common form of metabolic bone disease, leads to alterations in bone structure and density that have been shown to compromise the strength of spinal instrumentation. In addition, osteoporosis may contribute to high rates of fracture and instrumentation failure after long posterior spinal fusions, resulting in proximal junctional kyphosis and recurrent spinal deformity. As increasing numbers of elderly patients present for surgical intervention for degenerative and traumatic spinal pathologies, current and future generations of spine surgeons will increasingly be faced with the challenge of obtaining adequate fixation in osteoporotic bone. The purpose of this review is to familiarize the reader with the impact of osteoporosis on spinal instrumentation, the broad variety of techniques that have been developed for addressing these issues, and the biomechanical and clinical evidence in support of the use of these techniques. PMID- 26378364 TI - Experimental investigation on the minimum ignition temperature of hybrid mixtures of dusts and gases or solvents. AB - Investigations on the minimum ignition temperatures (MIT) of hybrid mixtures of dusts with gases or solvents were performed in the modified Godbert-Greenwald (GG) furnace. Five combustible dusts and six flammable gases (three ideal and three real) were used. The test protocol was according to EN 50281-2-1 for dust air mixtures whereas in the case of gases, solvents and hybrid mixtures this standard was used with slight modification. The experimental results demonstrated a significant decrease of the MIT of gas, solvent or dust and an increase in the likelihood of explosion when a small amount of dust, which was either below the minimum explosion concentration or not ignitable by itself, was mixed with gas and vice versa. For example, the MIT of toluene decreased from 540 degrees C to 455 degrees C when small amount of lycopodium was added. It was also confirmed that a hybrid mixture explosion is possible even when both dust and vapour or gas concentrations are respectively lower than their minimum explosion concentration (MEC) and lower explosion limit (LEL). Another example is CN4, the MEC of which of 304 g/m(3) decreased to 37 g/m(3) when propane was added, even though the concentrations of the gas was below its LEL. PMID- 26378365 TI - The influence of petroleum products on the methane fermentation process. AB - In this study the influence of the petroleum products: diesel fuel and spent engine oil on the sewage sludge digestion process and biogas production efficiency was investigated. Microbiological, chemical and enzymatic analyses were applied in the survey. It was revealed that the influence of the petroleum derivatives on the effectiveness of the methane fermentation of sewage sludge depends on the type of the petroleum product. Diesel fuel did not limit the biogas production and the methane concentration in the biogas, while spent engine oil significantly reduced the process efficacy. The changes in physical-chemical parameters, excluding COD, did not reflect the effect of the tested substances. The negative influence of petroleum products on individual bacterial groups was observed after 7 days of the process, while after 14 days probably some adaptive mechanisms appeared. The dehydrogenase activity assessment was the most relevant parameter to evaluate the effect of petroleum products contamination. Diesel fuel was probably used as a source of carbon and energy in the process, while the toxic influence was observed in case of spent engine oil. PMID- 26378366 TI - A novel method of utilizing permeable reactive kiddle (PRK) for the remediation of acid mine drainage. AB - Numerous technologies have been developed and applied to remediate AMD, but each has specific drawbacks. To overcome the limitations of existing methods and improve their effectiveness, we propose a novel method utilizing permeable reactive kiddle (PRK). This manuscript explores the performance of the PRK method. In line with the concept of green technology, the PRK method recycles industrial waste, such as steel slag and waste cast iron. Our results demonstrate that the PRK method can be applied to remediate AMD under optimal operational conditions. Especially, this method allows for simple installation and cheap expenditure, compared with established technologies. PMID- 26378367 TI - Evaluation of single and joint toxicity of perfluorooctane sulfonate and zinc to Limnodrilus hoffmeisteri: Acute toxicity, bioaccumulation and oxidative stress. AB - Perfluorooctane sulfonate (PFOS) and zinc have been detected in aquatic environment widely. In order to study the combined effects of PFOS and Zn, a series of experiments was conducted to explore the acute mortality, bioaccumulation and antioxidant status of Limnodrilus hoffmeisteri. The acute toxicity was evaluated by calculating 24h-EC50 values, and it was observed that 24h-EC50 values in single and joint treatments decreased with decreasing pH value or increasing exposure concentration. Toxic unit analysis suggested that the combined effects of the PFOS+Zn binary mixture were mostly simple addition, with 8 groups showing synergism and only one group showing antagonism. The analysis of internal Zn and PFOS concentration showed that the possible interaction between Zn and PFOS can affect the bioaccumulation of the two chemicals in L. hoffmeisteri. In addition, oxidative stress status was assessed by measuring oxidation-related biochemical parameters such as superoxide dismutase, glutathione peroxidase and malondialdehyde, and the integrated biomarker response index was estimated to rank the toxicity order. Exposures to Zn and PFOS were found to evoke some changes in the antioxidant defense system, and a strong self adaptive ability was noticed for L. hoffmeisteri after 10 d exposure. PMID- 26378368 TI - Highly Textured FeCo Thin Films Deposited by Low Temperature Pulsed Laser Deposition. AB - The effect of the deposition temperature (Tdep) on the crystallographic orientation of pulsed laser-deposited FeCo/MgO(100) thin film was determined by means of X-ray reflectivity and high resolution trasmission electron microscopy analysis and was correlated with the magnetic anisotropy properties measured by angle dependent hysteresis loops. Highly textured films with a bcc structure and very smooth surface were obtained even at room temperature, the film being [100] and [110] oriented, at Tdep=25 degrees C and 150 degrees C, respectively. The cubic symmetry is reflected in the angular dependence of remanent magnetization, showing a 4-fold character, whose in-plane distribution is consistent with the different crystallographic orientations of the films. The high structural quality, even at room temperature, is reflected in a high value of the saturation magnetization and low coercivity, matching the requirements for technological applications. PMID- 26378369 TI - Potential missing steps for a wide use of dried matrix spots in biomedical analysis. AB - Microsampling, mainly as DBS, has been significantly expanded in the biomedical and pharmaceutical communities in the last 10 years. In parallel, technology and methodology have evolved to overcome some of the issues associated with this sampling procedure. Despite the continuous developments and interest, only a few validated and routinely implemented clinical applications have arisen beyond the initial inborn screening. Based on the latest developments in this field, this perspective aims to discuss some of the missing steps (i.e., the habits to change, the Health Authorities acceptance and the shift for dried plasma generation), which may turn the current use of microsampling into an established and standard procedure in clinical and pharmaceutical analysis. PMID- 26378370 TI - Dose-Dependent Risk of Malformations With Antiepileptic Drugs: An Analysis of Data From the EURAP Epilepsy and Pregnancy Registry. PMID- 26378371 TI - Evaluation of Target Attainment of Vancomycin Area Under the Curve in Children With Methicillin-Resistant Staphylococcus Aureus Bacteremia. AB - BACKGROUND: Vancomycin is often required to treat methicillin-resistant Staphylococcus aureus bacteremia in children. Treatment failure occurs in up to 50% of adults and is associated with a 24-hour area under the curve/minimum inhibitory concentration (AUC24h/MIC) <400. We sought to identify patient factors associated with vancomycin AUC and whether AUC24h/MIC <400 was predictive of treatment failure in children. METHODS: Hospitalized children younger than 18 years with methicillin-resistant Staphylococcus aureus bacteremia receiving vancomycin were included in a retrospective cohort study. AUC24h was calculated using a validated pharmacokinetic model. Factors such as age, sex, underlying conditions, presence of foreign bodies, patient site of infection, and markers of illness severity were examined for an association with vancomycin AUC, and AUC24h/MIC was evaluated for an association with treatment failure. RESULTS: Subjects requiring intensive care unit support were significantly more likely to have higher vancomycin AUC24h and AUCavg than those subjects not needing intensive care unit support. Although vancomycin serum trough concentrations are predictive of vancomycin AUC, suboptimal exposure of vancomycin occurred in almost 20% of subjects despite trough concentrations within the target range. A relationship between vancomycin AUC24h/MIC and treatment failure could not be established. CONCLUSIONS: To ensure optimal AUC/MIC pharmacodynamic index, especially in critically ill patients, estimation of the AUC is critical. PMID- 26378372 TI - Quantifying the Effectiveness of Dose Individualization by Simulation for a Drug With Moderate Pharmacokinetic Variability. AB - BACKGROUND: Dose individualization can reduce variability in exposure. The objective of this work was to quantify, through pharmacokinetic (PK) simulation, the potential for reducing the variability in exposure by dose individualization for a drug with moderate PK variability between subjects and between occasions within a subject, and a narrow therapeutic window. METHODS: Using a population PK model that includes between-subject and between-occasion variability for apparent clearance, individual PK profiles in a trial of 300 subjects after a test dose were simulated. From the simulated data, datasets were created mimicking various sampling regimens (from single predose sample to full profile samples over 12 hours) on 1 or more occasions (1, 2, 3, 5, or 10 visits). Using these datasets, individual apparent clearance values were estimated, which were then used to calculate an individualized dose for a predefined target area under the concentration-time curve (AUC), based on the available formulation strengths. The proportion of people whose mean AUC was within a predefined therapeutic AUC range was calculated for the test (before) and the individualized dose (after), and compared between the different sampling scenarios. RESULTS: The maximum increase in proportion of subjects with an AUC within the range was 20%. To achieve this benefit, PK samples over 4 hours from 100 dosing occasions were required. As a result of the dose adjustment, the AUC of 7.3% of the subjects moved from inside the therapeutic range to outside of the range. CONCLUSIONS: This work shows how modeling and simulation can help assess the benefit and risk of dose individualization for a compound with variability between subjects and between occasions. The framework can be applied to similar situations with a defined set of conditions (eg, therapeutic window, tablet strengths, and PK and/or pharmacodynamic sampling scheme) to inform dose change and to assess the utility of dose individualization against certain success criteria. PMID- 26378373 TI - Rilpivirine Pharmacokinetics in 3 HIV-Positive Patients With Liver Cirrhosis Concomitantly Receiving Pantoprazole. PMID- 26378374 TI - Double-Balanced Graphene Integrated Mixer with Outstanding Linearity. AB - A monolithic double-balanced graphene mixer integrated circuit (IC) has been successfully designed and fabricated. The IC adopted the cross-coupled resistive mixer topology, integrating four 500 nm-gate-length graphene field-effect transistors (GFETs), four on-chip inductors, and four on-chip capacitors. Passive first-active-last fabrication flow was developed on 200 mm CMOS wafers. CMOS back end-of-line processes were utilized to realize most fabrication steps followed by GFET-customized processes. Test results show excellent output spectrum purity with suppressed radio frequency (RF) and local oscillation (LO) signals feedthroughs, and third-order input intercept (IIP3) reaches as high as 21 dBm. The results are compared with a fabricated single-GEFT mixer, which generates IIP3 of 16.5 dBm. Stand-alone 500 nm-gate-length GFETs feature cutoff frequency 22 GHz and maximum oscillation frequency 20.7 GHz RF performance. The double balanced mixer IC operated with off-chip baluns realizing a print-circuit-board level electronic system. It demonstrates graphene's potential to compete with other semiconductor technologies in RF front-end applications. PMID- 26378375 TI - Introduction: Reflections of Senior Therapists. AB - This introduction to this issue of JCLP: In Session ("Reflections of Senior Therapists") focuses on the multifaceted ways in which adult development influences what it means to be a psychotherapist and to do the work of psychotherapy. This issue brings together first person narratives written by a group of eminent psychotherapists as well as an empirical report, based on a major international survey, on the challenges, demands, and rewards experienced by senior therapists. Taken together, these essays provide a compelling case that not only can practicing psychotherapy during the later years of one's life continue to be fulfilling and meaningful, but also the lessons learned along the journey can make one an even wiser and more effective therapist than previously. Learning to do psychotherapy, like adult development itself, is not a process that at some point comes to an end, but one that is resumed again and again in every decade. These essays provide a rich array of information, insight, and guidance regarding the personal and professional experience of practicing therapy during every era of adulthood, including one's senior years. PMID- 26378376 TI - Simulation of Latex Film Formation Using a Cell Model in Real Space: Vertical Drying. AB - This paper presents a simulation tool applied to latex film formation by drying, a hybrid between a classical numerical resolution method using finite differences and cellular automata, and making use of object-oriented programming. It consists of dividing real space into cells and applying local physical laws to simulate the exchange of matter between neighboring cells. In a first step, the simulation was applied to the simple case of vertical drying of a latex containing only one population of monodisperse particles and water. Our results show how the distribution of latex particles evolves through the different drying stages due to a combination of diffusion, convection, and particle deformation. While repulsive interactions between the particles tend to favor homogeneous distributions in the first drying stage, concentration gradients that develop in opposite ways can be observed depending on the drying regime. The distributions, calculated in various cases, reproduce and extend several theoretical results and are in qualitative agreement with some experimental findings. PMID- 26378377 TI - On the formation of Cd-Zn sulfide photocatalysts from insoluble hydroxide precursors. AB - The formation of Cd-Zn sulfide solid solutions from mixed hydroxides under hydrothermal conditions is investigated in detail. The work specifically aims to understand the formation and the role of nanotwinned mixed sulfide particles that have been reported to show excellent performance in photocatalytic water splitting (Liu, M.; et al. Energy Environ. Sci. 2011, 4, 1372). The influence of additives, pH, autoclave tumbling, and the state of the mixed hydroxide precursor on the mixed sulfides was studied by XRD, XPS, TEM, DR UV-vis, and N2 physisorption. Cd-Zn sulfides are formed via a dissolution-precipitation mechanism. Agitation of the synthetic medium and the formation of soluble intermediate complexes during hydrothermal treatment suppress the formation of a hexagonal wurtzite crystal phase and improve the photocatalytic activity of the mixed sulfides. The role of additives can be understood in terms of complex formation, pH maintenance, and adsorption on the facets of growing crystallites. All Cd-Zn sulfide samples exhibit compositional inhomogeneities, resulting in XRD line broadening and decreased bandgaps as compared with the values predicted by Vegard's law. Detailed TEM analysis revealed that the samples with higher amounts of nanotwinned particles were significantly less active in water reduction. The influence of nanotwinned particles is discussed in terms of extended crystal defects and charge carrier recombination. PMID- 26378378 TI - Providing Oligonucleotides with Steric Selectivity by Brush-Polymer-Assisted Compaction. AB - Difficult biopharmaceutical characteristics of oligonucleotides, such as poor enzymatic stability, rapid clearance by reticuloendothelial organs, immunostimulation, and coagulopathies, limit their application as therapeutics. Many of these side effects are initiated via sequence-specific or nonsequence specific interactions with proteins. Herein, we report a novel form of brush polymer/DNA conjugate that provides the DNA with nanoscale steric selectivity: Hybridization kinetics with complementary DNA remains nearly unaffected, but interactions with proteins are significantly retarded. The relative lengths of the brush side chain and the DNA strand are found to play a critical role in the degree of selectivity. Being able to evade protein adhesion also improves in vivo biodistribution, thus making these molecular nanostructures promising materials for oligonucleotide-based therapies. PMID- 26378379 TI - Parenteral Prostanoid Use at a Tertiary Referral Center: A Retrospective Cohort Study. AB - BACKGROUND: Evidence-based guidelines recommend the use of parenteral prostaglandin (PP) therapy in patients with advanced pulmonary arterial hypertension (PAH). Despite this, many patients with PAH die without PP therapy. We sought to examine the frequency of PP use at a large referral center and characterize patients with PAH who died without receiving PP. METHODS: We conducted a single-center retrospective cohort analysis of consecutive patients with PAH between 2008 and 2012. Clinical data and cause of death were compared between patients with PAH treated with PP (PAH-PP) and those who were not but were not documented as poor PP candidates (PAH-nonPP). RESULTS: Of the 101 patients who received a diagnosis of PAH and died, 61 received PP therapy. Of the 40 patients not treated with PP, 10 did not have documented evaluations for PP therapy (PAH-nonPP) whereas 30 were not considered candidates or refused PP therapy. Compared with PAH-PP, PAH-nonPP had a longer 6-min walk distance, had a longer duration between time of diagnosis and date of worse functional class visit, were less likely to be diagnosed as functional class IV, and had significantly lower right atrial pressure. None of the PAH-nonPP died of progressive PAH. CONCLUSIONS: We found that most patients who die with PAH are evaluated for PP therapy at a large referral center and the small minority of PAH nonPP tended to have less severe disease and die of non-PAH-related causes. Our data suggest that at large pulmonary hypertension (PH) centers, the vast majority of patients who are appropriate candidates receive PP therapy. PMID- 26378382 TI - Impact of Protein Gel Porosity on the Digestion of Lipid Emulsions. AB - The present study sought to understand how the microstructure of protein gels impacts lipolysis of gelled emulsions. The selected system consisted of an oil-in water (o/w) emulsion embedded within gelatin gels. The gelatin-gelled emulsions consisted of a discontinuous network of aggregated emulsion droplets (mesoscale), dispersed within a continuous network of gelatin (microscale). The viscoelastic properties of the gelled emulsions were dominated by the rheological behavior of the gelatin, suggesting a gelatin continuous microstructure rather than a bicontinuous gel. A direct relationship between the speed of fat digestion and gel average mesh size was found, indicating that the digestion of fat within gelatin-gelled emulsions is controlled by the ability of the gel's microstructure to slow lipase diffusion to the interface of fat droplets. Digestion of fat was facilitated by gradual breakdown of the gelatin network, which mainly occurred via surface erosion catalyzed by proteases. Overall, this work has demonstrated that the lipolysis kinetics of gelled emulsions is driven by the microstructure of protein gels; this knowledge is key for the future development of microstructures to control fat digestion and/or the delivery of nutrients to different parts of the gastrointestinal tract. PMID- 26378383 TI - Effect of vitamin E succinate on the expression of the tumor necrosis factor related apoptosis-inducing ligand (TRAIL) receptor in gastric cancer cells and CD4(+) T cells. AB - Gastric malignancy, which shows poor prognosis, is one of the most frequent causes of cancer-associated deaths. Vitamin E succinate (VES) inhibits cell proliferation and induces apoptosis in a concentration- and time-dependent manner. We explored the effect of VES on the expression of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor in gastric cancer cells and CD4(+) T cells. On one hand, VES dose-dependently regulated the expression of the TRAIL receptor in gastric cancer cells. Moreover, the activation of the TRAIL receptor, death receptor 4 (DR4), and death receptor 5 (DR5) in gastric cancer cells increased for up to 12 h. On the other hand, the expression of TRAIL protein in human CD4(+) T cells was obviously upregulated in the presence of VES. On the basis of these findings, we combined VES and human CD4(+) T cells to induce apoptosis of MKN28 human gastric cancer cells. The results showed that VES induced higher gastric cancer cell apoptosis when combined with human CD4(+) T cells than when applied alone. We conclude that VES can induce the expression of TRAIL receptor in gastric cancer cells, as well as the expression of TRAIL in CD4(+) T cells. Overall, our results provide a theoretical basis for future immunotherapy studies. PMID- 26378384 TI - Reversal of Low-Grade Cerebral Edema After Lactulose/Rifaximin Therapy in Patients with Cirrhosis and Minimal Hepatic Encephalopathy. AB - OBJECTIVES: Decreased magnetization transfer ratio (MTR) in the brain characterizes cerebral edema (CE) in patients with liver cirrhosis, but the role of treatment on its reversibility has not been studied in patients who have minimal hepatic encephalopathy (MHE). This study was carried to evaluate the reversibility of CE with lactulose and rifaximin treatment in patients with MHE and role of ammonia, pro-inflammatory interleukins (IL-1, IL-6) and tumor necrosis factor (TNF)-alpha in its pathogenesis. METHODS: Twenty-three patients with cirrhosis (14 with MHE, 9 without MHE (NMHE)) and 6 healthy controls underwent ammonia, IL-1, IL-6, TNF-alpha estimation, and MTR in frontal white matter (FWM), parietal white matter (PWM), internal capsule (IC), and basal ganglia (BG). RESULTS: Ammonia was significantly higher in the cirrhosis group compared with controls and in MHE compared with the NMHE group. Ammonia correlated positively with IL-1 and IL-6. MTRs in FWM, PWM, IC, and BG were significantly lower in the MHE group compared with controls and in PWM, IC, and BG compared with the NMHE group. MHE patients showed significant MTR increase in FWM, PWM, and IC with treatment. IL-6 and ammonia had significant negative and significant positive psychometric hepatic encephalopathy score (PHES) correlation with MTR in various regions. CONCLUSIONS: This study, for the first time, demonstrated the reversibility of low-grade CE with treatment in patients with MHE. Negative correlation between ammonia, IL-6 levels, and MTR and positive correlation between PHES and MTR in MHE patients suggests the role of inflammation and ammonia in the genesis of low-grade CE. PMID- 26378385 TI - Isoprene in the Exhaled Breath is a Novel Biomarker for Advanced Fibrosis in Patients with Chronic Liver Disease: A Pilot Study. AB - OBJECTIVES: Analysis of volatile organic compounds (VOCs) in the exhaled breath can identify markers for alcoholic and nonalcoholic fatty liver disease. The aim of this pilot study was to investigate the utility of breath VOCs measured by mass spectrometry to diagnose advanced fibrosis in patients with chronic liver disease (CLD). METHODS: Patients undergoing liver biopsy were recruited. Fibrosis was determined by an experienced pathologist (F0-4) and advanced fibrosis was defined as F3-4. Exhaled breath and plasma samples were collected on the same day of the biopsy. Selective ion flow tube mass spectrometry (SIFT-MS) was used to analyze breath samples. Bonferroni correction was applied to decrease the false discovery rate. RESULTS: In all, 61 patients were included with a mean age of 50.7+/-9.9 years and 57% were male. Twenty patients (33%) had advanced fibrosis (F3-4), 44% had chronic hepatitis C, 30% had nonalcoholic fatty liver disease, and 26% had other CLD. SIFT-MS analysis of exhaled breath revealed that patients with advanced fibrosis had significantly lower values of six compounds compared with those without advanced fibrosis, P value <0.002 for all. Isoprene was found to have the highest accuracy for the prediction of advanced fibrosis with an area under the receiver operating characteristics curve of 0.855 (95% confidence interval: 0.762, 0.948). The median breath isoprene level in patients with F3-4 was 13.5[8.7, 24.7] p.p.b. compared with 40.4[26.2, 54.1] for those with F0-2, P value <0.001. Isoprene is an endogenous VOC that is a byproduct of cholesterol biosynthesis. CONCLUSIONS: Isoprene is a potential biomarker for advanced fibrosis that deserves further validation. PMID- 26378387 TI - [Current shortcomings in the treatment of cryptorchidism - analysis performed by a paediatrician]. AB - Cryptorchidism is the most common disorder in paediatric surgery in the Western world and a major risk factor for subfertility and malignancy. In 2009, German national guidelines were changed to recommend that treatment for undescended testes should be completed by the age of 1 instead of 2. However, the share of boys undergoing orchidopexy for cryptorchidism within the first year of life has only marginally increased in response to the guideline of the Association of the Scientific Medical Societies in Germany (AWMF). The number of orchidopexies performed in children below the age of 1 is too low both in Germany as well as internationally. The majority of primary care physicians treating children do not seem to be aware of this discrepancy between guideline recommendations and average actual age at orchidopexy. Moreover, a considerable number of cryptorchidism cases seem to be due to secondary ascent of the testis - an underappreciated condition that usually occurs at school age. Consequently, the timing of orchidopexy in primary undescended testes must be optimised. Therefore, education of parents and primary care physicians regarding the necessity of early orchidopexy and frequent testicular examinations even beyond infancy is mandatory to improve the prognosis of cryptorchidism regarding subfertility and malignancy. Further studies are needed to clarify the reasons for the large number of late orchidopexies. PMID- 26378388 TI - [Female urethral obstruction and bladder neck stenosis - fact or myth - how to proceed]. AB - The female urethra is probably the most neglected organ in women. Female urethral stricture and primary bladder neck obstruction are rare clinical entities. Traditional and new surgical techniques have been described for the treatment of female urethral stricture. However, they are based on limited data. There is no consensus on best management. The techniques of urethroplasty all have a higher mean success rate (80-94%) than urethral dilatation (< 50%), albeit with shorter mean follow-up. Urethroplasty performed by experienced surgeons appears to be a feasible option in women who have failed urethral dilatation, although there is a lack of high-level evidence to recommend one technique over another.Primary bladder neck obstruction (PBNO) is a condition in which the bladder neck fails to open adequately during voiding. This leads to increased striated sphincter activity or obstruction of urinary flow without another anatomic cause being present, for example an obstruction caused by genitourinary prolapse in women. Watchful waiting, pharmacotherapy and surgical intervention are possible treatments. PMID- 26378386 TI - Prostaglandin I2 Signaling and Inhibition of Group 2 Innate Lymphoid Cell Responses. AB - RATIONALE: Group 2 innate lymphoid cells (ILC2s) robustly produce IL-5 and IL-13, cytokines central to the asthma phenotype; however, the effect of prostaglandin (PG) I2 on ILC2 function is unknown. OBJECTIVES: To determine the effect of PGI2 on mouse and human ILC2 cytokine expression in vitro and the effect of endogenous PGI2 and the PGI2 analog cicaprost on lung ILC2s in vivo. METHODS: Flow-sorted bone marrow ILC2s of wild-type (WT) and PGI2 receptor-deficient (IP(-/-)) mice were cultured with IL-33 and treated with the PGI2 analog cicaprost. WT and IP(-/ ) mice were challenged intranasally with Alternaria alternata extract for 4 consecutive days to induce ILC2 responses, and these were quantified. Prior to A. alternata extract, challenged WT mice were treated with cicaprost. Human flow sorted peripheral blood ILC2s were cultured with IL-33 and IL-2 and treated with the PGI2 analog cicaprost. MEASUREMENT AND MAIN RESULTS: We demonstrate that PGI2 inhibits IL-5 and IL-13 protein expression by IL-33-stimulated ILC2s purified from mouse bone marrow in a manner that was dependent on signaling through the PGI2 receptor IP. In a mouse model of 4 consecutive days of airway challenge with an extract of A. alternata, a fungal aeroallergen associated with severe asthma exacerbations, endogenous PGI2 signaling significantly inhibited lung IL-5 and IL 13 protein expression, and reduced the number of lung IL-5- and IL-13-expressing ILC2s, as well as the mean fluorescence intensity of IL-5 and IL-13 staining. In addition, exogenous administration of a PGI2 analog inhibited Alternaria extract induced lung IL-5 and IL-13 protein expression, and reduced the number of lung IL 5- and IL-13-expressing ILC2s and the mean fluorescence intensity of IL-5 and IL 13 staining. Finally, a PGI2 analog inhibited IL-5 and IL-13 expression by human ILC2s that were stimulated with IL-2 and IL-33. CONCLUSIONS: These results suggest that PGI2 may be a potential therapy to reduce the ILC2 response to protease-containing aeroallergens, such as Alternaria. PMID- 26378389 TI - [Chronic pelvic pain: alternative treatment methods]. AB - Chronic pelvic pain has a negative impact on quality of life, resulting in a tremendous cost of illness. This condition has a multifactorial etiology and its treatment is often a frustrating experience for patients and therapists alike. Therefore, patients frequently initiate alternative medical treatment methods, which are explained below. PMID- 26378390 TI - [Asymptomatic kidney stones: active surveillance vs. treatment]. AB - The prevalence of kidney stones is increasing worldwide. Asymptomatic non obstructing kidney stones are increasingly detected as an incidental finding on radiologic imaging, which has been performed more frequently over the last decades. Beside the current interventional treatment modalities such as extracorporeal shockwave lithotripsy (ESWL), ureterorenoscopy (URS) and percutaneous nephrolithotomy (PNL), active surveillance of asymptomatic kidney stones has been a focus of discussion lately, not only for attending physicians, but even more so for patients. The current German and European guidelines recommend active surveillance for patients with asymptomatic kidney stones if no interventional therapy is mandatory because of pain or medical factors. Herein we review the current literature on risks and benefits of active surveillance of asymptomatic non-obstructing kidney stones. PMID- 26378391 TI - [In Process Citation]. PMID- 26378392 TI - [In Process Citation]. PMID- 26378393 TI - Antifibrinolytic therapy in aneurysmal subarachnoid hemorrhage increases the risk for deep venous thrombosis: A case-control study. AB - OBJECTIVES: Aneurysm re-rupture is associated with significant morbidity and mortality in aneurysmal subarachnoid hemorrhage (aSAH). While antifibrinolytics reduce aneurysm re-rupture rates, they have been associated with hydrocephalus, delayed cerebral ischemia, and venous thrombosis. We performed a case-control study in patients enrolled in the Cerebral Aneurysm Renin Angiotensin System (CARAS) study to evaluate the impact of short course (<48 h) E-aminocaproic acid (EACA) on deep venous thrombosis (DVT) rates. PATIENTS AND METHODS: A case control study design was utilized to evaluate the effect of EACA on DVT formation. All cases and controls were obtained from the CARAS study, a prospective, blinded study assessing the association of polymorphisms in the renin angiotensin system and aSAH. RESULTS: One hundred and twenty-eight eligible patients were enrolled in CARAS. Overall, 48 (37.5%) patients were screened for DVT, 57 (44.5%) patients were treated with short course (<48 h) EACA, and 8 (6.3%) patients suffered a re-rupture (4 treated with EACA). Ten patients (7.8%) were diagnosed with DVT as evidenced by Doppler US and represent the cases. Twenty controls without evidence of a DVT matched for age, sex, race, tobacco history, Hunt-Hess score, Fisher grade, body mass index, and length of stay were identified from the remaining pool of 118 patients. EACA was found to significantly increase the risk of DVT formation in patients with aSAH (OR 8.49, CI 1.27-77.1). CONCLUSION: Short course (<48 h) administration of EACA in patients with aneurysmal subarachnoid hemorrhage is associated with an 8.5 times greater risk of DVT formation. PMID- 26378394 TI - Inadequate hepcidin serum concentrations predict incident type 2 diabetes mellitus. AB - BACKGROUND: Type 2 diabetes mellitus (T2DM) is closely associated with elevated body iron stores. The hormone hepcidin is the key regulator of iron homeostasis. Inadequately low hepcidin levels were recently reported in subjects with manifest T2DM. We investigated whether alterations of hepcidin levels precede the manifestation of T2DM and predict T2DM development independently of established risk conditions. METHODS: This prospective population-based study included 675 subjects aged 50-89 years, 51.9% of whom were female. Hepcidin levels were measured by gold standard tandem mass spectrometry. Diabetes was diagnosed according to American Diabetes Association criteria, and incident diabetes was recorded between baseline in 2000 and 2010. RESULTS: The baseline hepcidin-to ferritin ratio in subjects that subsequently developed diabetes during follow-up was reduced on average by 29.8% as compared with subjects with normal glucose tolerance (95% confidence interval, -50.7% to -0.2%; p = 0.049). After adjustment for age, sex, and serum ferritin, higher hepcidin levels were associated with reduced risk of incident diabetes (hazard ratio per 1-unit higher log2 hepcidin, 0.80; 95% confidence interval, 0.64-0.98; p = 0.035; 33 events). Additional adjustment for established diabetes risk factors and determinants of hepcidin concentration did not appreciably change these results (HR, 0.81; 95% CI, 0.66 0.99). Likewise, inadequately low hepcidin levels were also detected in subjects with prevalent T2DM (n = 76). CONCLUSIONS: Hepcidin levels that are inadequately low in relation to body iron stores are an independent predictor for incident T2DM and may contribute to diabetes-related tissue iron overload. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26378396 TI - Agonism and dominance in female blue monkeys. AB - Agonistic behavior features prominently in hypotheses that explain how social variation relates to ecological factors and phylogenetic constraints. Dominance systems vary along axes of despotism, tolerance, and nepotism, and comparative studies examine cross-species patterns in these classifications. To contribute to such studies, we present a comprehensive picture of agonistic behavior and dominance relationships in wild female blue monkeys (Cercopithecus mitis), an arboreal guenon, with data from 9 groups spanning 18 years. We assessed where blue monkeys fall along despotic, tolerant, and nepotistic spectra, how their dominance system compares to other primates, primarily cercopithecines, and whether their agonistic behavior matches socioecological model predictions. Blue monkeys showed low rates of mainly low-intensity agonism and little counter aggression. Rates increased with rank and group size. Dominance asymmetry varied at different organizational levels, being more pronounced at the level of interactions than dyad or group. Hierarchies were quite stable, had moderate-to high linearity and directional consistency and moderate steepness. There was clear maternal rank inheritance, but inconsistent adherence to Kawamura's rules. There was little between-group variation, although hierarchy metrics showed considerable variation across group-years. Overall, blue monkeys have moderately despotic, moderately tolerant, and nepotistic dominance hierarchies. They resemble other cercopithecines in having significantly linear and steep hierarchies with a generally stable, matriline-based structure, suggesting a phylogenetic basis to this aspect of their social system. Blue monkeys most closely match Sterck et al.'s [1997] Resident-Nepotistic-Tolerant dominance category, although they do not fully conform to predictions of any one socioecological model. Our results suggest that socioecological models might better predict variation within than across clades, thereby incorporating both ecological variables and phylogenetic constraints. Our findings also highlight the need for clearer definitions of socioecologically relevant dominance categories, which would ideally derive from quantitative measures of dominance behavior. Intraspecific and methodological variation may, however, be a challenge. PMID- 26378395 TI - Clinical Presentation of Ocular Surface Squamous Neoplasia in Kenya. AB - IMPORTANCE: There is a trend toward treating conjunctival lesions suspected to be ocular surface squamous neoplasia (OSSN) based on the clinical impression. OBJECTIVE: To describe the presentation of OSSN and identify clinical features that distinguish it from benign lesions and subsequently evaluate their recognizability. DESIGN, SETTING, AND PARTICIPANTS: Prospective multicenter study in Kenya from July 2012 through July 2014 of 496 adults presenting with conjunctival lesions. One histopathologist examined all specimens. Six additional masked ophthalmologists independently examined photographs from 100 participants and assessed clinical features. EXPOSURES: Comprehensive history, slitlamp examination, and photography before excision biopsy. MAIN OUTCOMES AND MEASURES: Frequency of clinical features in OSSN and benign lesions were recorded. Proportions and means were compared using chi2, Fisher exact test, or t test as appropriate. Interobserver agreement was estimated using the kappa statistic. Examiners' assessments were compared with a reference. RESULTS: Among 496 participants, OSSN was the most common (38%) histological diagnosis, followed by pterygium (36%) and actinic keratosis (19%). Patients with OSSN were slightly older (mean [SD] age, 41 [11.6] vs 38 [10.9] years; P = .002) and tended to have lower levels of education than patients with benign lesions (P = .001). Females predominated (67% of OSSN vs 64% of benign lesions; P = .65). Human immunodeficiency virus infection was common among patients with OSSN (74%). The most common location was the nasal limbus (61% OSSN vs 78% benign lesions; P < .001). Signs more frequent in OSSN included feeder vessels (odds ratio [OR], 5.8 [95% CI, 3.2-10.5]), moderate inflammation (OR, 3.5 [95% CI, 1.8-6.8]), corneal involvement (OR, 2.7 [95% CI, 1.8-4.0]), leukoplakia (OR, 2.6 [95% CI, 1.7-3.9]), papilliform surface (OR, 2.1 [95% CI, 1.3-3.5]), pigmentation (OR, 1.5 [95% CI, 1.0-2.2]), temporal location (OR, 2.0 [95% CI, 1.2-3.2]), circumlimbal location (6.7% vs 0.3%; P < .001), severe inflammation (6.7% vs 0.3%; P < .001), and larger mean (SD) diameter (6.8 [3.2] vs 4.8 [2.8] mm; P < .001). All OSSN signs were also observed in benign lesions. There was slight to fair interobserver agreement in assessment of most signs and diagnosis (kappa, 0.1-0.4). The positive predictive value of clinical appearance in identifying OSSN was 54% (interquartile range, 51%-56%) from photographs in which prevalence was 32%. CONCLUSIONS AND RELEVANCE: With overlapping phenotypes and modest interobserver agreement, OSSN and benign conjunctival lesions are not reliably distinguished clinically. Point-of-care diagnostic tools may help. PMID- 26378397 TI - An Expedited Care Pathway with Ambulatory Brachial Plexus Analgesia Is a Cost effective Alternative to Standard Inpatient Care after Complex Arthroscopic Elbow Surgery: A Randomized, Single-blinded Study. AB - BACKGROUND: Common standard practice after complex arthroscopic elbow surgery includes hospital admission for 72 h. The authors hypothesized that an expedited care pathway, with 24 h of hospital admission and ambulatory brachial plexus analgesia and continuous passive motion at home, results in equivalent elbow range of motion (ROM) 2 weeks after surgery compared with standard 72-h hospital admission. METHODS: A randomized, single-blinded study was conducted after obtaining approval from the research ethics board. Forty patients were randomized in a 1:1 ratio using a computer-generated list of random numbers into an expedited care pathway group (24-h admission) and a control group (72-h admission). They were treated equally aside from the predetermined hospital length of stay. RESULTS: Patients in the control (n = 19) and expedited care pathway (n = 19) groups achieved similar elbow ROM 2 weeks (119 +/- 18 degrees and 121 +/- 15 degrees, P = 0.627) and 3 months (130 +/- 18 vs. 130 +/- 11 degrees, P = 0.897) postoperatively. The mean difference in elbow ROM at 2 weeks was 2.6 degrees (95% CI, -8.3 to 13.5). There were no differences in analgesic outcomes, physical function scores, and patient satisfaction up to 3 months postoperatively. Total hospital cost of care was 15% lower in the expedited care pathway group. CONCLUSION: The results suggest that an expedited care pathway with early hospital discharge followed by ambulatory brachial plexus analgesia and continuous passive motion at home is a cost-effective alternative to 72 h of hospital admission after complex arthroscopic elbow surgery. PMID- 26378398 TI - Activation of Adenosine Monophosphate-activated Protein Kinase Suppresses Neuroinflammation and Ameliorates Bone Cancer Pain: Involvement of Inhibition on Mitogen-activated Protein Kinase. AB - BACKGROUND: Activation of adenosine monophosphate-activated kinase (AMPK) has been associated with the inhibition of inflammatory nociception and the attenuation of morphine antinociceptive tolerance. In this study, the authors investigated the impact of AMPK activation through resveratrol treatment on bone cancer pain. METHODS: The nociception was assessed by measuring the incidence of foot withdrawal in response to mechanical indentation in rats (n = 8). Cytokine expression was measured using quantitative polymerase chain reaction (n = 8). Cell signalings were assayed by western blot (n = 4) and immunohistochemistry (n = 5). The microglial cell line BV-2, primary astrocytes, and neuron-like SH-SY5Y cells were cultured to investigate the in vitro effects. RESULTS: Resveratrol and 5-amino-1-beta-D-ribofuranosyl-imidazole-4-carboxamide, the AMPK activators, significantly attenuated bone cancer pain in rats with tumor cell implantation (TCI; threshold of mechanical withdrawal, resveratrol vs. vehicle: 10.1 +/- 0.56 vs. 4.1 +/- 0.37; 5-amino-1-beta-D-ribofuranosyl-imidazole-4-carboxamide vs. vehicle: 8.2 +/- 0.17 vs. 4.1 +/- 0.37, mean +/- SEM); these effects were reversed by the AMPK inhibitor compound C (compound C vs. resveratrol: 6.2 +/- 1.35 vs. 10.1 +/- 0.56, mean +/- SEM). Resveratrol has an AMPK-dependent inhibitory effect on TCI-evoked astrocyte and microglial activation. The antinociceptive effects of resveratrol were partially mediated by the reduced phosphorylation of mitogen-activated protein kinases and decreased production of proinflammatory cytokines in an AMPK-dependent manner. Furthermore, resveratrol potently inhibited inflammatory factors-mediated protein kinase B/mammalian target of rapamycin signaling in neurons. Acute pain evoked by proinflammatory cytokines in the spinal cord was significantly attenuated by resveratrol. CONCLUSIONS: AMPK activation in the spinal glia by resveratrol may have utility in the treatment of TCI-induced neuroinflammation, and our results further implicate AMPK as a novel target for the attenuation of bone cancer pain. PMID- 26378399 TI - Trends in Pain Medicine Liability. AB - BACKGROUND: The authors examined changes in the frequency of pain medicine malpractice claims and associated treatment modalities and outcomes over time. METHODS: The authors analyzed trends in pain medicine claims from 1980 to 2012 in the Anesthesia Closed Claims Project database by binary logistic regression on year of event. Pain procedures in claims from 2000 to 2012 were compared with the proportion of pain procedures reported to the National Anesthesia Clinical Outcomes Registry in 2010-2014. RESULTS: Malpractice claims for pain medicine increased from 3% of 2,966 total malpractice claims in the Anesthesia Closed Claims Project database in 1980-1989 to 18% of 2,743 anesthesia claims in 2000 2012 (odds ratio [OR], 1.088 per year; 95% CI, 1.078 to 1.098; P < 0.001). Outcomes in pain claims became more severe over time, with increases in death and permanent disabling injury (OR, 1.094 per year; P < 0.001). Nonneurolytic cervical injections increased to 27% of pain claims in 2000-2012 (OR, 1.054; P < 0.001), whereas National Anesthesia Clinical Outcomes Registry demonstrates that lumbar injections are a more common procedure. Claims associated with medication management increased to 17% of pain claims in 2000-2012 (OR, 1.116 per year; P < 0.001). CONCLUSIONS: Pain medicine claims have increased over time and have increased in severity. Claims related to cervical procedures were out of proportion to the frequency with which they are performed. These liability findings suggest that pain specialists should aggressively continue the search for safer and more effective therapies. PMID- 26378400 TI - Relationships Among Daytime Napping and Fatigue, Sleep Quality, and Quality of Life in Cancer Patients. AB - BACKGROUND: The relationships among napping and sleep quality, fatigue, and quality of life (QOL) in cancer patients are not clearly understood. OBJECTIVE: The aim of the study was to determine whether daytime napping is associated with nighttime sleep, fatigue, and QOL in cancer patients. METHODS: In total, 187 cancer patients were recruited. Daytime napping, nighttime self-reported sleep, fatigue, and QOL were assessed using a questionnaire. Objective sleep parameters were collected using a wrist actigraph. RESULTS: According to waking-after-sleep onset measurements, patients who napped during the day experienced poorer nighttime sleep than did patients who did not (t = -2.44, P = .02). Daytime napping duration was significantly negatively correlated with QOL. Patients who napped after 4 PM had poorer sleep quality (t = -1.93, P = .05) and a poorer Short-Form Health Survey mental component score (t = 2.06, P = .04) than did patients who did not. Fatigue, daytime napping duration, and sleep quality were significant predictors of the mental component score and physical component score, accounting for 45.7% and 39.3% of the variance, respectively. CONCLUSIONS: Daytime napping duration was negatively associated with QOL. Napping should be avoided after 4 PM. IMPLICATIONS FOR PRACTICE: Daytime napping affects the QOL of cancer patients. Future research can determine the role of napping in the sleep hygiene of cancer patients. PMID- 26378401 TI - Spiritual Well-being May Reduce the Negative Impacts of Cancer Symptoms on the Quality of Life and the Desire for Hastened Death in Terminally Ill Cancer Patients. AB - BACKGROUND: Spirituality is a central component of the well-being of terminally ill cancer patients. OBJECTIVE: The aim of this study was to examine the mediating or moderating role of spiritual well-being in reducing the impact of cancer-related symptoms on quality of life and the desire for hastened death in terminally ill cancer patients. METHODS: Eighty-five terminally ill cancer patients were assessed using the Taiwanese version of the M. D. Anderson Symptom Inventory, the Functional Assessment of Cancer Therapy-General, the Functional Assessment of Chronic Illness Therapy-Spiritual Well-being, the Beck Hopelessness Scale, and the Schedule of Attitudes Toward Hastened Death. RESULTS: Spiritual well-being was significantly negatively correlated with symptom severity (r = 0.46, P < .01). Symptom severity negatively correlated with quality of life (r = 0.54) and positively correlated with hopelessness (r = 0.51, P < .01) and the desire for hastened death (r = 0.61, P < .01). Spiritual well-being was a partial mediator and moderator between symptom severity and quality of life. Spiritual well-being was a partial mediator between symptom severity and the desire for hastened death. The meaning subscale of spiritual well-being was a more significant predictor of the desire for hastened death and quality of life than the faith subscale was. CONCLUSION: Spiritual well-being may reduce the negative impacts of cancer on quality of life and the desire for hastened death. IMPLICATIONS FOR PRACTICE: Appropriate spiritual care may reduce the negative impact of severe cancer symptoms on quality of life and the desire for hastened death in terminally ill cancer patients. PMID- 26378402 TI - The Psychometric Properties of the Chinese Version of the Fatigue Scale for Children. AB - BACKGROUND: The availability of a valid and reliable instrument that accurately assesses the level of fatigue among childhood cancer survivors is a prerequisite for developing and evaluating interventions designed to reduce fatigue. There is a lack of such an instrument for use in the Hong Kong Chinese context. OBJECTIVE: The aim of the study was to examine the psychometric properties of the Chinese version of the Fatigue Scale for Children. In particular, confirmatory factor analysis was conducted to examine its factorial structure. METHODS: A convenience sample of 200 Hong Kong Chinese children surviving cancer was recruited in an outpatient clinic. The psychometric properties of the Chinese version of the Fatigue Scale for Children were assessed. RESULTS: The content validity index was 0.83. There was a strong positive correlation between children's level of fatigue and depressive symptoms (r = 0.53) and a strong negative correlation between children's levels of fatigue and quality of life (r = -0.54). The mean levels of fatigue of the survivor group were significantly lower than those of those hospitalized with cancer, but significantly higher than those of their healthy counterparts. Confirmatory factor analysis indicated that there were 3 factors underlying the Chinese version of the Fatigue Scale for Children. CONCLUSION: The study adds further evidence that the Chinese version of the Fatigue Scale for Children can be used as a reliable and valid tool in assessing cancer-related fatigue among Chinese children who have survived cancer. IMPLICATIONS FOR PRACTICE: The translated scale can be used to develop and evaluate appropriate fatigue reduction interventions. PMID- 26378403 TI - Molecular characterization of Tasmanian aquabirnaviruses from 1998 to 2013. AB - Tasmanian aquabirnaviruses (TABVs) have been isolated intermittently since 1998 from healthy Atlantic salmon Salmo salar and rainbow trout Oncorhynchus mykiss farmed in Macquarie Harbour, Tasmania, Australia. However, beginning in 2011, TABVs have been isolated from rainbow trout in association with mortality events. To determine if recent molecular changes in TABV were contributing to increased mortalities, next generation sequencing was undertaken on 14 TABVs isolated from 1998 to 2013. Sequencing of both genome segments and analysis of the 5 viral proteins they encode revealed that minimal changes had occurred in the past 15 yr. Of the amino acid changes detected only 1, alanine to aspartic acid at position 139 of the minor structural VP3 protein, was unique to the recent disease events. The most dramatic changes observed were in the length of the non structural VP5 protein varying from 43 to 133 amino acids. However, the amino acid substitution in VP3 and variable VP5 length were unlikely to have resulted in increased TABV pathogenicity. The genome of a novel Australian aquabirnavirus, Victorian trout aquabirnavirus (VTAB) was also sequenced and compared to TABV isolates. PMID- 26378404 TI - Dactylogyrus intermedius parasitism enhances Flavobacterium columnare invasion and alters immune-related gene expression in Carassius auratus. AB - The monogenean Dactylogyrus intermedius and the bacterium Flavobacterium columnare are 2 common pathogens in aquaculture. The objective of the present study was to examine the effect of prior parasitism by D. intermedius on the susceptibility of goldfish to F. columnare and to explore the potential immune mechanisms related to the parasite infection. A F. columnare challenge trial was conducted between D. intermedius-parasitized and non-parasitized goldfish. The F. columnare load in gill, kidney, spleen and liver were compared. The expression of immune-related genes (IL-1beta2, TNF-alpha1, TGF-beta, iNOS-a, C3 and Lyz) in gill and kidney of D. intermedius-only infected and uninfected control fish were evaluated. D. intermedius-parasitized goldfish exhibited higher mortality and significantly higher loads (3051 to 537,379 genome equivalents [GEs] mg(-1)) of F. columnare, which were 1.13 to 50.82-fold higher than non-parasitized fish (389 to 17,829 GEs mg(-1)). Furthermore, the immune genes IL-1beta2, TNF-alpha1, iNOS a and Lyz were up-regulated while the TGF-beta and C3 were down-regulated in the gill and kidney of parasite-infected fish compared to the non-parasitized controls. The down-regulation TGF-beta and C3 was especially noteworthy, as this might indicate the suppression of the host immune functions due to the parasitism by D. intermedius. Taken together, these data demonstrate that parasite infection can enhance bacterial invasion and presents a hypothesis, based on gene expression data, that modulation of host immune response could play a role. PMID- 26378405 TI - Larval trematodes Paronatrema mantae and Copiatestes sp. parasitize Gulf of California krill (Nyctiphanes simplex, Nematoscelis difficilis). AB - During 4 quantitative-systematic oceanographic cruises at 99 sampling stations in the Gulf of California (January and July 2007, August 2012, and June 2013), we found 2 trematode species (non-encysted mesocercaria stage) parasitizing the hemocoel of 2 krill species at near-shore locations. Copiatestes sp. parasitized Nematoscelis difficilis in January 2007, and Paronatrema mantae parasitized Nyctiphanes simplex in July 2007. Both trematode species had an intensity of 1 parasite per host. This is the first endoparasite known for N. difficilis, the first record of P. mantae infecting zooplankton, and the first confirmed trematode parasitizing krill species in the Gulf of California. We provide quantitative evidence that these 2 trematode species infect krill with considerably low station prevalence (0.03-0.16%) and low population abundances (<1.2 trematodes 1000 m(-3)). A review of trematodes parasitizing krill indicates that syncoeliid trematodes also have (with few exceptions) low population densities and prevalence and lower species diversity than previously thought (suggesting a broader zoogeographic distribution range of these parasites). Due to the low host specificity of syncoeliid trematodes that typically infect more than 1 secondary intermediate host species in their complex life cycle, we propose that N. simplex and N. difficilis are intermediate hosts (although non conspicuous) for the transmission of syncoeliid trematodes in the Gulf of California. PMID- 26378406 TI - Genetic diversity of culturable Vibrio in an Australian blue mussel Mytilus galloprovincialis hatchery. AB - Bacillary necrosis associated with Vibrio species is the common cause of larval and spat mortality during commercial production of Australian blue mussel Mytilus galloprovincialis. A total of 87 randomly selected Vibrio isolates from various stages of rearing in a commercial mussel hatchery were characterised using partial sequences of the ATP synthase alpha subunit gene (atpA). The sequenced isolates represented 40 unique atpA genotypes, overwhelmingly dominated (98%) by V. splendidus group genotypes, with 1 V. harveyi group genotype also detected. The V. splendidus group sequences formed 5 moderately supported clusters allied with V. splendidus/V. lentus, V. atlanticus, V. tasmaniensis, V. cyclitrophicus and V. toranzoniae. All water sources showed considerable atpA gene diversity among Vibrio isolates, with 30 to 60% of unique isolates recovered from each source. Over half (53%) of Vibrio atpA genotypes were detected only once, and only 7 genotypes were recovered from multiple sources. Comparisons of phylogenetic diversity using UniFrac analysis showed that the culturable Vibrio community from intake, header, broodstock and larval tanks were phylogenetically similar, while spat tank communities were different. Culturable Vibrio associated with spat tank seawater differed in being dominated by V. toranzoniae-affiliated genotypes. The high diversity of V. splendidus group genotypes detected in this study reinforces the dynamic nature of microbial communities associated with hatchery culture and complicates our efforts to elucidate the role of V. splendidus group bacteria in vibriosis. PMID- 26378407 TI - Changes in the bacterial community associated with black band disease in a Red Sea coral, Favia sp., in relation to disease phases. AB - Changes of the black band disease (BBD)-associated microbial consortium on the surface of a Favia sp. coral colony were assessed in relation to the different disease phases. A number of highly active bacterial groups changed in numbers as the BBD disease signs changed. These included Gamma- and Epsilonproteobacteria, Bacteroidetes and Firmicutes groups. One cyanobacterium strain, BGP10_4ST (FJ210722), was constantly present in the disease interface and adjacent tissues of the affected corals, regardless of disease phase. The dynamics of the operational taxonomic units (OTUs) of this BBD-specific strain provide a marker regarding the disease phase. The disease's active phase is characterized by a wide dark band progressing along the tissue-skeleton interface and by numerous bacterial OTUs. Cyanobacterial OTUs decreased in numbers as the disease signs waned, perhaps opening a niche for additional microorganisms. Even when black band signs disappeared there was a consistent though low abundance of the BBD specific cyanobacteria (BGP10_4ST), and the microbial community of the disease skeleton interface remained surprisingly similar to the original band community. These results provide an indication that the persistence of even low numbers of this BBD-specific cyanobacterium in coral tissues during the non-active (or subclinical) state could facilitate reinitiation of BBD signs during the following summer. This may indicate that this bacterium is major constituent of the disease and that its persistence and ability to infiltrate the coral tissues may act to facilitate the assembly of the other BBD-specific groups of bacteria. PMID- 26378408 TI - Vertebral column deformities in white-beaked dolphins from the eastern North Atlantic. AB - Five white-beaked dolphins Lagenorhynchus albirostris with outwardly vertebral kyphosis, kyphoscoliosis or lordosis were identified during a photo identification survey of over 400 individuals (2002-2013) in Faxafloi and Skjalfandi Bays, Iceland. In addition, 3 stranding reports from Denmark, The Netherlands and the UK were analysed, providing both external observation and post mortem details of axial deviations of the vertebral column in this species. Two of the free-ranging cases and 2 of the stranded specimens appeared to have an acquired disease, either as a direct result of trauma, or indirectly from trauma/wound and subsequent infection and bony proliferation, although we were unable to specifically identify the causes. Our data represent a starting point to understand vertebral column deformations and their implications in white beaked dolphins from the eastern North Atlantic. We recommend for future necropsy cases to conduct macro- and microscopic evaluation of muscle from both sides of the deformed region, in order to assess chronic or acute conditions related to the vertebral deformations and cause of death. PMID- 26378409 TI - Aeromonas dhakensis pneumonia and sepsis in a neonate Risso's dolphin Grampus griseus from the Mediterranean Sea. AB - A neonate Risso's dolphin Grampus griseus was found stranded alive on a beach in Catalonia, Spain. Rehabilitation attempts were unsuccessful and it died 2 d later, showing pneumonia and sepsis. A pure bacterial culture was obtained from all tissues and blood and identified as Aeromonas hydrophila using the API 20NE. However, sequencing the rpoD gene showed that the strain in fact belongs to A. dhakensis, making this the first report of fatal haemorrhagic-necrotizing pneumonia and sepsis due to this species in a marine mammal. The A. dhakensis strain GMV-704 produced beta-haemolysis, possessed several virulence genes and showed sensitivity to several antimicrobials. This study provides a new potential host for A. dhakensis, and its potential virulence in dolphins and its presence in the marine environment may warrant considering this species a potential threat to marine mammals. PMID- 26378410 TI - Fatal Erysipelothrix rhusiopathiae septicemia in two Atlantic dolphins (Stenella frontalis and Tursiops truncatus). AB - We describe gross, histopathologic, ultrastructural, immunohistochemical, and microbiologic features of acute septicemia by Erysipelothrix rhusiopathiae in an Atlantic spotted dolphin Stenella frontalis and an Atlantic bottlenose dolphin Tursiops truncatus. Generalized lymphadenomegaly and widespread hemorrhages were the most consistent macroscopic findings. Tricavitary effusion and icterus were noted in one individual. Histologically, all organs examined showed numerous variably sized bacillary bacterial emboli (Gram-positive; Ziehl-Neelsen negative), typically associated with systemic congestion, edema, hemorrhages, and fibrinocellular thrombi. These bacteria were frequently intravascular, either extracellular or intramonocytic/macrophagic, and to a lesser extent, free within the interstitium of parenchymal organs. In both cases, microbiological analysis yielded E. rhusiopathiae. A primary anti-E. rhusiopathiae antibody created in mice from one of the strains isolated allowed positive immunohistochemical detection. Electron microscopy and dual immunohistochemistry with lysozyme and MAC387 antibodies confirmed the intramacrophagic location of the bacilli. E. rhusiopathiae, a known multispecies and zoonotic agent, should be considered as a potential etiologic agent in septicemia cases in free-ranging individuals of these dolphin species. PMID- 26378411 TI - Epidemiology, Prognostic Factors, and Treatment of Malignant Submandibular Gland Tumors: A Population-Based Cohort Analysis. AB - IMPORTANCE: Malignant tumors of the submandibular gland are uncommon, leading to limited information regarding prognostic factors and difficulty in evaluating treatment modalities. OBJECTIVE: To investigate the correlates of survival in patients with primary malignant tumors of the submandibular gland. DESIGN, SETTING, AND PARTICIPANTS: Data from 2626 patients with a diagnosis of primary tumors of the submandibular gland between 1973 and 2011 in the Surveillance, Epidemiology, and End Results database were used in a retrospective population based cohort analysis. Kaplan-Meier analysis along with multivariate Cox regression analysis was performed to determine prognostic factors in overall survival (OS) and disease-specific survival (DSS). INTERVENTIONS: Patients were treated with surgery, radiation therapy, both, or neither. MAIN OUTCOMES AND MEASURES: Overall and disease-specific survival. RESULTS: We identified 2626 patients with a diagnosis of primary malignant tumors of the submandibular gland, 52.9% male and 47.1% female, with a mean (range) age of 61.3 (7-101) years. Adenoid cystic carcinoma (36.0%) was the most prevalent histologic subtype, followed by squamous cell carcinoma (18.1%), mucoepidermoid carcinoma (16.9%), and adenocarcinoma (13.7%). Kaplan-Meier analysis demonstrated an OS and DSS of 65% and 74%at 2 years, 54% and 67% at 5 years, and 40% and 60% at 10 years, respectively. Multivariate Cox regression analysis revealed independent predictors of OS and DSS to be age (HR, 1.04 [95% CI, 1.03-1.04], P < .001; HR, 1.02 [95% CI, 1.01-1.03], P < .001), sex (HR, 0.69 [95% CI, 0.57-0.84], P < .001; HR, 0.73 [95% CI, 0.56-0.96], P = .02), tumor grade (HR, 1.47 [95% CI, 1.19 1.81], P < .001; HR, 1.67 [95% CI, 1.25-2.25], P = .001), stage at presentation (HR, 1.56 [95% CI, 1.41-1.72], P < .001; HR, 1.96 [95% CI, 1.69-2.28], P < .001), and surgical resection (HR, 0.55 [95% CI, 0.41-0.74], P < .001; HR, 0.51 [95% CI, 0.35-0.75], P = .001). CONCLUSIONS AND RELEVANCE: We report, to our knowledge, the largest study to date focused on correlates of survival in submandibular gland malignant neoplasms. Multivariate analysis found that older age at diagnosis, high tumor grade, and later stage at presentation were correlated with decreased survival whereas female sex and surgical resection were correlated with increased survival. In addition, a 3-cm tumor cutoff size was demonstrated above which was associated with a significantly less favorable prognosis. Radiation therapy had mixed association with survival, dependent on tumor size and subtype. PMID- 26378413 TI - Repeated Aortic Balloon Valvuloplasty in Elderly Patients With Aortic Stenosis Who Are Not Candidates for Definitive Treatment. AB - AIMS: A sizable group of patients with symptomatic aortic stenosis can undergo neither surgical aortic valve replacement nor transcatheter aortic valve implantation. The aim of this study was to assess the potential role of repeated balloon aortic valvuloplasty (BAV) in these patients. METHODS: Within our local prospective BAV registry, we retrospectively selected 105 patients who underwent >=2 BAV procedures between 2005 and 2012 because of persisting contraindications to definitive treatment after first BAV. In-hospital outcome and incidence of adverse events at 1, 2, and 3 years were assessed. Mean age was 84 +/- 6 years, mean logistic EuroSCORE was 23.6 +/- 13.4%. RESULTS: No intraprocedural deaths occurred. In-hospital events for the 224 BAV procedures were: myocardial infarction, 4%; stroke, 0.9%; vascular complications, 8% (1.8% major); and bleedings, 5.9% (life threatening, 0.9%; major, 1.8%). Acute aortic regurgitation occurred in 6 cases and was always resolved during procedures. Median follow-up was 785 days. Second BAVs showed fewer vascular complications (P<.001) and bleedings (P<.001). Bleedings (odds ratio [OR], 6.88; 95% confidence interval [CI], 1.58-29.88) and vascular complications (OR, 4.8; 95% CI, 1.19-19.31) occurring after the first procedure were independent predictors for subsequent adverse events. All-cause mortality at 1, 2, and 3 years was 15.2%, 41.3%, and 57.2%. Hospital readmission for heart failure was 40.7% at 1-year follow-up, 61.7% at 2-year follow-up, and 77.6% at 3-year follow-up. CONCLUSION: BAV is associated with poor long-term clinical outcome. However, when no other therapeutic options are feasible, a strategy of repeated palliative BAV appears to be safe and is potentially associated with improved clinical outcomes. PMID- 26378412 TI - Binding of FGF2 to FGFR2 in an autocrine mode in trophectoderm cells is indispensable for mouse blastocyst formation through PKC-p38 pathway. AB - Fibroblast growth factors (FGF1, FGF2 and FGF4) and fibroblast growth factor receptors (FGFR1, FGFR2, FGFR3 and FGFR4) have been reported to be expressed in preimplantation embryos and be required for their development. However, the functions of these molecules in trophectoderm cells (TEs) that lead to the formation of the blastocyst as well as the underlying mechanism have not been elucidated. The present study has demonstrated for the first time that endogenous FGF2 secreted by TEs can regulate protein expression and distribution in TEs via the FGFR2-mediated activation of PKC and p38, which are important for the development of expanded blastocysts. This finding provides the first explanation for the long-observed phenomenon that only high concentrations of exogenous FGFs have effects on embryonic development, but in vivo the amount of endogenous FGFs are trace. Besides, the present results suggest that FGF2/FGFR2 may act in an autocrine fashion and activate the downstream PKC/p38 pathway in TEs during expanded blastocyst formation. PMID- 26378414 TI - Comparison of Iodixanol and Ioxaglate for Coronary Optical Coherence Tomography Imaging. AB - BACKGROUND: The impact of contrast type on coronary imaging using optical coherence tomography (OCT) has received limited study. We compared OCT imaging obtained using the non-ionic, iso-osmolar iodixanol with the ionic, low-osmolar ioxaglate. METHODS: Twenty-two vessels in 20 patients were imaged twice using manual injection of iodixanol and ioxaglate in random order. OCT images were analyzed at 1 mm intervals to determine lumen area, artifact diameter and area, as well as stent strut coverage and malapposition in OCT pullbacks that included stents. RESULTS: There were no complications related to OCT imaging or to contrast administration. A total of 2184 cross-sections (1092 with iodixanol and 1092 with ioxaglate) were analyzed. Compared with iodixanol, imaging using ioxaglate provided similar mean lumen area (6.21 +/- 2.83 mm2 vs 6.27 +/- 2.83 mm2; Spearman's rho, 0.982), mean minimum lumen diameter (2.47 +/- 0.59 mm vs 2.50 +/- 0.58 mm; Spearman's rho, 0.939), and mean maximum lumen diameter (2.99 +/- 0.71 mm vs 3.01 +/- 0.70 mm; Spearman's rho, 0.964), but lower mean artifact area per cross-section (0.099 +/- 0.325 mm2 vs 0.068 +/- 0.329 mm2; P<.001). Analyses of 3303 stent struts in 388 cross-sections (194 with iodixanol and 194 with ioxaglate) demonstrated similar strut malapposition rates (11.82% vs 13.90%; P=.10) and strut coverage (41.92% vs 40.33%; P=.35). CONCLUSIONS: Compared with iodixanol, OCT imaging using ioxaglate provided similar lumen and diameter measurements and stent strut characterization, but smaller area of artifact. PMID- 26378415 TI - Impact of Switching From Prasugrel to Clopidogrel Shortly After a Percutaneous Coronary Intervention Without a Loading Dose of Clopidogrel. AB - OBJECTIVE: To determine the safety and efficacy of administering prasugrel at the time of percutaneous coronary intervention (PCI), and switching to clopidogrel, without reloading. BACKGROUND: Prasugrel has faster onset of action and appears to be of greater benefit than clopidogrel, particularly early after PCI. However, long-term prasugrel increases bleeding. Many physicians at Geisinger Medical Center (GMC) administer prasugrel before PCI and switch to clopidogrel afterward. The safety and efficacy of this strategy has not been studied. METHODS: We performed a retrospective study using electronic medical records and identified patients at GMC who underwent PCI between February 1, 2009 and January 31, 2012 and received a loading dose of prasugrel with a subsequent switch to clopidogrel, without reloading. The primary endpoint was major adverse cardiovascular event (MACE), defined as death, myocardial infarction (MI), stroke, or stent thrombosis, 7 days after the first dose of clopidogrel. Secondary endpoints included MACE at 30 days, individual MACE components at 7 and 30 days post procedure, and bleeding as defined by the Bleeding Academic Research Consortium (BARC) at 1 day and 30 days. RESULTS: A total of 151 patients met inclusion criteria. One patient suffered a MACE on day 7 (0.7%; 95% confidence interval, 0.03%-3.33%). One patient had an MI between 8-30 days. Two patients had BARC bleeding (type 2 and type 3b) 30 days post PCI. CONCLUSIONS: In this small, retrospective analysis, the results of loading patients with prasugrel for PCI and switching them to clopidogrel without a loading dose appear to be encouraging. PMID- 26378416 TI - Ionic liquids as diluents in solvent extraction: first evidence of supramolecular aggregation of a couple of extractant molecules. AB - Ionic liquids have many favorable properties over conventional diluents in solvent extraction. They provide an environmentally benign feature, adjustable polarity and, in some cases, higher extraction performances that remain however not predictable. As it may have a major role in extraction mechanisms, we evidence the supramolecular aggregation of HDEHP/TOPO extractant molecules in the [OMim][NTf2] ionic liquid. PMID- 26378417 TI - Zerovalent Fe, Co and Ni nanoparticle toxicity evaluated on SKOV-3 and U87 cell lines. AB - We have considered nanoparticles (NPs) of Fe, Co and Ni, three transition metals sharing similar chemical properties. NP dissolution, conducted by radioactive tracer method and inductively coupled plasma mass spectrometry, indicated that NiNPs and FeNPs released in the medium a much smaller amount of ions than that released by Co NPs. The two considered methodological approaches, however, gave comparable but not identical results. All NPs are readily internalized by the cells, but their quantity inside the cells is less than 5%. Cytotoxicity and gene expression experiments were performed on SKOV-3 and U87 cells. In both cell lines, CoNPs and NiNPs were definitely more toxic than FeNPs. Real-time polymerase chain reaction experiments aimed to evaluate modifications of the expression of genes involved in the cellular stress response (HSP70, MT2A), or susceptible to metal exposure (SDHB1 and MLL), or involved in specific cellular processes (caspase3, IQSEC1 and VMP1), gave different response patterns in the two cell lines. HSP70, for example, was highly upregulated by CoNPs and NiNPs, but only in SKOV-3 cell lines. Overall, this work underlines the difficulties in predicting NP toxicological properties based only on their chemical characteristics. We, consequently, think that, at this stage of our knowledge, biological effects induced by metal-based NPs should be examined on a case-by case basis following studies on different in vitro models. Moreover, with the only exception of U87 exposed to Ni, our results suggest that metallic NPs have caused, on gene expression, similar effects to those caused by their corresponding ions. PMID- 26378418 TI - Intermittent vs Continuous Androgen Deprivation Therapy for Prostate Cancer: A Systematic Review and Meta-analysis. AB - IMPORTANCE: Androgen deprivation is the standard therapy for patients with advanced or recurrent prostate cancer. However, this treatment causes adverse effects, alters quality of life, and may lead to castration-resistant disease. Intermittent androgen deprivation has been studied as an alternative. OBJECTIVE: To conduct a systematic review and meta-analysis comparing the efficacy and tolerability of intermittent vs continuous androgen deprivation therapy in patients with prostate cancer. DATA SOURCES: We searched Cochrane CENTRAL, Medline, Embase, Web of Science, Biosis, National Technical Information Service, OpenSIGLE, and Google Scholar from inception of each database through March 2014. References from published guidelines, reviews, and other relevant articles were also considered. STUDY SELECTION: We selected randomized clinical trials comparing intermittent vs continuous androgen deprivation therapy in patients with prostate cancer. DATA EXTRACTION AND SYNTHESIS: Two reviewers performed study selection, data abstraction, and risk of bias assessment. We calculated hazard ratios (HRs) with the inverse variance method and risk ratios with the Mantel-Haenszel method, using random effect models. A noninferiority analysis was conducted for overall survival with a margin of 1.15 for the upper boundary of the HR. We assessed heterogeneity using the I2 index. MAIN OUTCOMES AND MEASURES: Primary outcomes were overall survival and quality of life. Secondary outcomes were cancer-specific survival, progression-free survival, time to castration resistance, skeletal-related events, and adverse effects. RESULTS: From 10 510 references, we included 22 articles from 15 trials (6856 patients) published between 2000 and 2013. All but 1 study had an unclear or high risk of bias. We observed no significant difference between intermittent and continuous therapy for overall survival (HR, 1.02; 95% CI, 0.93-1.11; 8 trials, 5352 patients), cancer-specific survival (HR, 1.02; 95% CI, 0.87-1.19; 5 trials, 3613 patients), and progression-free survival (HR, 0.94; 95% CI, 0.84-1.05; 4 trials, 1774 patients). There was minimal difference in patients' self-reported quality of life between the 2 interventions. Most trials observed an improvement in physical and sexual functioning with intermittent therapy. CONCLUSIONS AND RELEVANCE: Intermittent androgen deprivation was not inferior to continuous therapy with respect to the overall survival. Some quality-of-life criteria seemed improved with intermittent therapy. Intermittent androgen deprivation can be considered as an alternative option in patients with recurrent or metastatic prostate cancer. PMID- 26378420 TI - Collaboration Between JECME and JCEHP: Providing New Opportunities for CME Researchers and Practitioners. PMID- 26378419 TI - Social problem-solving and social adjustment in paediatric traumatic brain injury. AB - OBJECTIVE: Little is known regarding the predictors of social deficits that occur following childhood traumatic brain injury (TBI). The current study sought to investigate social problem solving (SPS) and its relationship to social adjustment after TBI. METHODS: Participants included 8-13 year old children, 25 with severe TBI, 57 with complicated mild-to-moderate TBI and 61 with orthopaedic injuries (OI). Children responded to scenarios involving negative social situations by selecting from a fixed set of choices their causal attribution for the event, their emotional reaction to the event and how they would behave in response. Parent ratings of social behaviours and classmate friendship nominations and sociometric ratings were obtained for a sub-set of all participants. RESULTS: Children with severe TBI were less likely than children with OI to indicate they would attribute external blame or respond by avoiding the antagonist; they were more likely to indicate they would feel sad and request adult intervention. Although several SPS variables had indirect effects on the relationship between TBI and social adjustment, clinical significance was limited. CONCLUSIONS: The findings suggest that, while children with TBI display atypical SPS skills, SPS cannot be used in isolation to accurately predict social adjustment. PMID- 26378421 TI - Using a Critical Incident Scenario With Virtual Humans to Assess Educational Needs of Nurses in a Postanesthesia Care Unit. AB - INTRODUCTION: During critical incidents, teamwork failures can compromise patient safety. This study provides evidence that virtual humans can be used in simulated critical incidents to assess the learning needs of health professionals, and provide important information that can inform the development of continuing education programs in patient safety. We explored the effectiveness of information transfer during a devolving medical situation between postanesthesia care unit (PACU) nurses and a virtual attending physician. METHODS: We designed a three-stage scenario: tutorial, patient transfer, and critical incident. We developed 2 checklists to assess information transfer: Critical Patient Information and Interprofessional Communication Skills. All participants were videotaped; 2 raters reviewed all videos and assessed performance using the checklists. RESULTS: Participants (n = 43) who completed all 3 stages scored 62.3% correct on critical patient information transfer and 61.6% correct on interprofessional communication skills. Almost 87% missed a fatal drug error. The checklists measured each item on a 1/0 (done/not) calculation. Additionally, no relationship was found between years of nursing experience and performance on either checklist. DISCUSSION: The PACU nurses in this study did not consistently share critical information with an attending (virtual) physician during a critical incident, and most missed a fatal dosage error. These findings strongly suggest a crucial need for additional structured team training among practicing health care teams, and they demonstrate the utility of using virtual humans to simulate team members. PMID- 26378422 TI - Is the Cognitive Complexity of Commitment-to-Change Statements Associated With Change in Clinical Practice? An Application of Bloom's Taxonomy. AB - INTRODUCTION: This study categorizes 4 practice change options, including commitment-to-change (CTC) statements using Bloom's taxonomy to explore the relationship between a hierarchy of CTC statements and implementation of changes in practice. Our hypothesis was that deeper learning would be positively associated with implementation of planned practice changes. METHODS: Thirty-five family physicians were recruited from existing practice-based small learning groups. They were asked to use their usual small-group process while exploring an educational module on peripheral neuropathy. Part of this process included the completion of a practice reflection tool (PRT) that incorporates CTC statements containing a broader set of practice change options-considering change, confirmation of practice, and not convinced a change is needed ("enhanced" CTC). The statements were categorized using Bloom's taxonomy and then compared to reported practice implementation after 3 months. RESULTS: Nearly all participants made a CTC statement and successful practice implementation at 3 months. By using the "enhanced" CTC options, additional components that contribute to practice change were captured. Unanticipated changes accounted for one-third of all successful changes. Categorizing statements on the PRT using Bloom's taxonomy highlighted the progression from knowledge/comprehension to application/analysis to synthesis/evaluation. All PRT statements were classified in the upper 2 levels of the taxonomy, and these higher-level (deep learning) statements were related to higher levels of practice implementation. CONCLUSION: The "enhanced" CTC options captured changes that would not otherwise be identified and may be worthy of further exploration in other CME activities. Using Bloom's taxonomy to code the PRT statements proved useful in highlighting the progression through increasing levels of cognitive complexity-reflecting deep learning. PMID- 26378423 TI - Mentoring Faculty: A US National Survey of Its Adequacy and Linkage to Culture in Academic Health Centers. AB - INTRODUCTION: The aims of this study were to (1) describe the quantity and quality of mentoring faculty in US academic health centers (AHCs), (2) measure associations between mentoring and 12 dimensions that reflect the culture of AHCs, and (3) assess whether mentoring predicts seriously contemplating leaving one's institution. METHODS: During 2007-2009, our National Initiative on Gender, Culture and Leadership in Medicine (C - Change) conducted a cross-sectional study of faculty from 26 representative AHCs in the United States using the 74-item C - Change Faculty Survey to assess relationships of faculty characteristics and various aspects of the institutional culture (52% response rate). Among the 2178 eligible respondents (assistant, associate, and full professors), we classified their mentoring experience as either inadequate, neutral, or positive. RESULTS: In this national sample, 43% of the 2178 respondents had inadequate mentoring; only 30% had a positive assessment of mentoring. There was no statistical difference by sex, minority status, or rank. Inadequate mentoring was most strongly associated with less institutional support, lower self-efficacy in career advancement, and lower scores on the trust/relationship/inclusion scale. The percent of faculty who had seriously considered leaving their institution was highest among those who had inadequate mentoring (58%), compared to those who were neutral (28%) or had positive mentoring (14%) (all paired comparisons, p < .001). DISCUSSION: In a national survey of faculty of US AHCs, mentoring was frequently inadequate and this was associated with faculty contemplating leaving their institutions. Positive mentoring, although less prevalent, was associated with many other positive dimensions of AHCs. PMID- 26378424 TI - Using LinkedIn for Continuing Community of Practice Among Hand Surgeons Worldwide. AB - BACKGROUND: Hand surgeons need continuing professional development due to rapid advancement in the field. Traditional approaches have proven to be challenging due to the nature of surgical practice and other demands. Social media sites have shown the potential to build an online community of practice. METHODS: One of the authors (VR) started Hand Surgery International on LinkedIn in February 2011. RESULTS: The number of members increased from 38 in the beginning to 4106 members by August 13, 2015, with members from all over the world. Half of them are from plastic surgery, with 16.8% hand and 17.8% orthopedic surgery; 63.8% of them are consultants. There were 151 discussion topics, which generated 1238 comments at an average of 8.2 comments per discussion thread. The topics focused on management of difficult patients, seeking consensus, and searching information. The features participants found most useful included case-based discussion, polls/surveys, and network opportunity. Members perceived the LinkedIn community as user-friendly and easy to use. It does not require significant technical knowledge. For the question "How would you rate the overall ease of using this platform?" 42% answered "strongly agree" and 37% "agree". CONCLUSION: The LinkedIn group serves as an effective means for continuing professional development for hand surgeons. PMID- 26378425 TI - Group Peer Mentoring: An Answer to the Faculty Mentoring Problem? A Successful Program at a Large Academic Department of Medicine. AB - INTRODUCTION: To address a dearth of mentoring and to avoid the pitfalls of dyadic mentoring, the authors implemented and evaluated a novel collaborative group peer mentoring program in a large academic department of medicine. METHODS: The mentoring program aimed to facilitate faculty in their career planning, and targeted either early-career or midcareer faculty in 5 cohorts over 4 years, from 2010 to 2014. Each cohort of 9-12 faculty participated in a yearlong program with foundations in adult learning, relationship formation, mindfulness, and culture change. Participants convened for an entire day, once a month. Sessions incorporated facilitated stepwise and values-based career planning, skill development, and reflective practice. Early-career faculty participated in an integrated writing program and midcareer faculty in leadership development. RESULTS: Overall attendance of the 51 participants was 96%, and only 3 of 51 faculty who completed the program left the medical school during the 4 years. All faculty completed a written detailed structured academic development plan. Participants experienced an enhanced, inclusive, and appreciative culture; clarified their own career goals, values, strengths and priorities; enhanced their enthusiasm for collaboration; and developed skills. DISCUSSION: The program results highlight the need for faculty to personally experience the power of forming deep relationships with their peers for fostering successful career development and vitality. The outcomes of faculty humanity, vitality, professionalism, relationships, appreciation of diversity, and creativity are essential to the multiple missions of academic medicine. PMID- 26378426 TI - Organizational Change, Leadership, and the Transformation of Continuing Professional Development: Lessons Learned From the American College of Cardiology. AB - There is a need for a transformational change in clinical education. In postgraduate medical education we have traditionally had a faculty-centric model. That is, faculty knew what needed to be taught and who were the best teachers to teach it. They built the agenda, and worked with staff to follow Accreditation Council for Continuing Medical Education (ACCME) accreditation criteria and manage logistics. Changes in the health care marketplace now demand a learner centric model-one that embraces needs assessments, identification of practice gaps relative to competency, development of learning objectives, contemporary adult learning theory, novel delivery systems, and measurable outcomes. This article provides a case study of one medical specialty society's efforts to respond to this demand. PMID- 26378427 TI - Networked Learning and Network Science: Potential Applications to Health Professionals' Continuing Education and Development. AB - Prior interpersonal relationships and interactivity among members of professional associations may impact the learning process in continuing medical education (CME). On the other hand, CME programs that encourage interactivity between participants may impact structures and behaviors in these professional associations. With the advent of information and communication technologies, new communication spaces have emerged that have the potential to enhance networked learning in national and international professional associations and increase the effectiveness of CME for health professionals. In this article, network science, based on the application of network theory and other theories, is proposed as an approach to better understand the contribution networking and interactivity between health professionals in professional communities make to their learning and adoption of new practices over time. PMID- 26378428 TI - Encouraging Reflection and Change in Clinical Practice: Evolution of a Tool. AB - This article describes the systematic development and gradual transformation of a tool to guide participants in a continuing medical education program to reflect on their current practices and to make commitments to change. The continuous improvement of this tool was influenced by evolving needs of the program, reviews of relevant educational literature, feedback from periodic program surveys, interviews with group facilitators, and results from educational research studies. As an integral component of the educational process used in the Practice Based Small Group Learning Program, the current tool is designed to help family physicians think about what has been learned during each educational session and examine issues related to the implementation of evidence-based changes into their clinical practice. Lessons learned will be highlighted. Both the developmental processes employed and the practice reflection tool itself have applicability to other educational environments that focus on continuing professional development. PMID- 26378429 TI - Considering "Nonlinearity" Across the Continuum in Medical Education Assessment: Supporting Theory, Practice, and Future Research Directions. AB - The purpose of this article is to propose new approaches to assessment that are grounded in educational theory and the concept of "nonlinearity." The new approaches take into account related phenomena such as "uncertainty," "ambiguity," and "chaos." To illustrate these approaches, we will use the example of assessment of clinical reasoning, although the principles we outline may apply equally well to assessment of other constructs in medical education. Theoretical perspectives include a discussion of script theory, assimilation theory, self regulated learning theory, and situated cognition. Assessment examples to include script concordance testing, concept maps, self-regulated learning microanalytic technique, and work-based assessment, which parallel the above-stated theories, respectively, are also highlighted. We conclude with some practical suggestions for approaching nonlinearity. PMID- 26378430 TI - Mitigating false-positive associations in rare disease gene discovery. AB - Clinical sequencing is expanding, but causal variants are still not identified in the majority of cases. These unsolved cases can aid in gene discovery when individuals with similar phenotypes are identified in systems such as the Matchmaker Exchange. We describe risks for gene discovery in this growing set of unsolved cases. In a set of rare disease cases with the same phenotype, it is not difficult to find two individuals with the same phenotype that carry variants in the same gene. We quantify the risk of false-positive association in a cohort of individuals with the same phenotype, using the prior probability of observing a variant in each gene from over 60,000 individuals (Exome Aggregation Consortium). Based on the number of individuals with a genic variant, cohort size, specific gene, and mode of inheritance, we calculate a P value that the match represents a true association. A match in two of 10 patients in MECP2 is statistically significant (P = 0.0014), whereas a match in TTN would not reach significance, as expected (P > 0.999). Finally, we analyze the probability of matching in clinical exome cases to estimate the number of cases needed to identify genes related to different disorders. We offer Rare Disease Match, an online tool to mitigate the uncertainty of false-positive associations. PMID- 26378435 TI - Special Issue: Materials Research at Tianjin Collaborative Innovation Center of Chemical Science and Engineering. PMID- 26378438 TI - Catecholamines and acetylcholine are key regulators of the interaction between microbes and the immune system. AB - Recent studies suggest that catecholamines (CAs) and acetylcholine (ACh) play essential roles in the crosstalk between microbes and the immune system. Host cholinergic afferent fibers sense pathogen-associated molecular patterns and trigger efferent cholinergic and catecholaminergic pathways that alter immune cell proliferation, differentiation, and cytokine production. On the other hand, microbes have the ability to produce and degrade ACh and also regulate autogenous functions in response to CAs. Understanding the role played by these neurotransmitters in host-microbe interactions may provide valuable information for the development of novel therapies. PMID- 26378439 TI - Toward a better understanding of the central consequences of intestinal inflammation. AB - Inflammatory bowel diseases (IBDs), which include Crohn's disease and ulcerative colitis, are inflammatory diseases of the gastrointestinal tract. Quality of life for IBD patients is negatively affected by associated pain and gastrointestinal dysfunction, but also by serious behavioral symptoms that include depression, anxiety, fatigue, and cognitive dysfunction. Because these behavioral comorbidities are poorly understood, we have investigated them in a rat model of IBD caused by infusion of a hapten (trinitrobenzene sulfonic acid (TNBS)) into the lower colon. TNBS colitis has many similarities to Crohn's disease, and we have found that it is associated with changes in central nervous system function. TNBS-treated animals have lowered seizure thresholds, which resolve following remission, and hippocampal slices from such animals display increased excitability. There are significant changes in excitatory, AMPA receptor-mediated transmission, in part due to increased numbers of AMPA receptors lacking the GluR2 subunit. Long-term potentiation and depression are reduced in colitic animals, and the synaptic alterations are reversed if microglial activation and tumor necrosis factor alpha synthesis within the brain are blocked. PMID- 26378441 TI - Correction: Human and Murine Clonal CD8+ T Cell Expansions Arise during Tuberculosis Because of TCR Selection. PMID- 26378440 TI - Time Adaptation Shows Duration Selectivity in the Human Parietal Cortex. AB - Although psychological and computational models of time estimation have postulated the existence of neural representations tuned for specific durations, empirical evidence of this notion has been lacking. Here, using a functional magnetic resonance imaging (fMRI) adaptation paradigm, we show that the inferior parietal lobule (IPL) (corresponding to the supramarginal gyrus) exhibited reduction in neural activity due to adaptation when a visual stimulus of the same duration was repeatedly presented. Adaptation was strongest when stimuli of identical durations were repeated, and it gradually decreased as the difference between the reference and test durations increased. This tuning property generalized across a broad range of durations, indicating the presence of general time-representation mechanisms in the IPL. Furthermore, adaptation was observed irrespective of the subject's attention to time. Repetition of a nontemporal aspect of the stimulus (i.e., shape) did not produce neural adaptation in the IPL. These results provide neural evidence for duration-tuned representations in the human brain. PMID- 26378443 TI - The Genus Cerion (Gastropoda: Cerionidae) in the Florida Keys. AB - The systematic relationships and phylogeography of Cerion incanum, the only species of Cerion native to the Florida Keys, are reviewed based on partial sequences of the mitochondrial COI and 16S genes derived from 18 populations spanning the range of this species and including the type localities of all four described subspecies. Our samples included specimens of Cerion casablancae, a species introduced to Indian Key in 1912, and a population of C. incanum x C. casablancae hybrids descended from a population of C. casablancae introduced onto Bahia Honda Key in the same year. Molecular data did not support the partition of C. incanum into subspecies, nor could populations be apportioned reliably into subspecies based on morphological features used to define the subspecies. Phylogenetic analyses affirmed the derived relationship of C. incanum relative to other cerionids, and indicated a Bahamian origin for the Cerion fauna of southern Florida. Relationships among the populations throughout the Keys indicate that the northernmost populations, closest to the Tomeu paleoislands that had been inhabited by Cerion petuchi during the Calabrian Pleistocene, are the oldest. The range of Cerion incanum expanded as the archipelago that is the Florida Keys was formed since the lower Tarantian Pleistocene by extension from the northeast to the southwest, with new islands populated as they were formed. The faunas of the High Coral Keys in the northeast and the Oolite Keys in the southwest, both with large islands that host multiple discontinuous populations of Cerion, are each composed of well supported clades that are characterized by distinctive haplotypes. In contrast, the fauna of the intervening Low Coral Keys consist of a heterogeneous series of populations, some with haplotypes derived from the High Coral Keys, others from the Oolite Keys. Individuals from the C. incanum x C. casablancae hybrid population inhabiting the southeastern coast of Bahia Honda Key were readily segregated based on their mitogenome lineage, grouping either with C. incanum or with C. casablancae from Indian Key. Hybrids with C. casablancae mitogenomes had haplotypes that were more divergent from their parent mitogenome than were hybrids with C. incanum mitogenomes. PMID- 26378442 TI - Decline of Phosphotransfer and Substrate Supply Metabolic Circuits Hinders ATP Cycling in Aging Myocardium. AB - Integration of mitochondria with cytosolic ATP-consuming/ATP-sensing and substrate supply processes is critical for muscle bioenergetics and electrical activity. Whether age-dependent muscle weakness and increased electrical instability depends on perturbations in cellular energetic circuits is unknown. To define energetic remodeling of aged atrial myocardium we tracked dynamics of ATP synthesis-utilization, substrate supply, and phosphotransfer circuits through adenylate kinase (AK), creatine kinase (CK), and glycolytic/glycogenolytic pathways using 18O stable isotope-based phosphometabolomic technology. Samples of intact atrial myocardium from adult and aged rats were subjected to 18O-labeling procedure at resting basal state, and analyzed using the 18O-assisted HPLC-GC/MS technique. Characteristics for aging atria were lower inorganic phosphate Pi[18O], gamma-ATP[18O], beta-ADP[18O], and creatine phosphate CrP[18O] 18O labeling rates indicating diminished ATP utilization-synthesis and AK and CK phosphotransfer fluxes. Shift in dynamics of glycolytic phosphotransfer was reflected in the diminished G6P[18O] turnover with relatively constant glycogenolytic flux or G1P[18O] 18O-labeling. Labeling of G3P[18O], an indicator of G3P-shuttle activity and substrate supply to mitochondria, was depressed in aged myocardium. Aged atrial myocardium displayed reduced incorporation of 18O into second (18O2), third (18O3), and fourth (18O4) positions of Pi[18O] and a lower Pi[18O]/gamma-ATP[18 O]-labeling ratio, indicating delayed energetic communication and ATP cycling between mitochondria and cellular ATPases. Adrenergic stress alleviated diminished CK flux, AK catalyzed beta-ATP turnover and energetic communication in aging atria. Thus, 18O-assisted phosphometabolomics uncovered simultaneous phosphotransfer through AK, CK, and glycolytic pathways and G3P substrate shuttle deficits hindering energetic communication and ATP cycling, which may underlie energetic vulnerability of aging atrial myocardium. PMID- 26378444 TI - Results of Vertebral Augmentation Treatment for Patients of Painful Osteoporotic Vertebral Compression Fractures: A Meta-Analysis of Eight Randomized Controlled Trials. AB - BACKGROUND: In 2009 two RCTs were publicated to question the efficacy of vertebroplasty comparing with sham treatment (ST) in the New England Journal of Medicine (NEJM), which provoked an academic debate on the efficacy of PVA. The purposes of our study were to compare clinical differences in pain relief, spinal functional outcomes, and overall quality of life between PVA and CT for painful osteoporotic VCFs. METHODS: We searched PubMed, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials and Web of Knowledge from January 1980 to June 2013 with Medical Subject Headings terms and keywords. Risk of bias in the included studies was assessed in accordance with the Cochrane risk of bias tool. In this Meta-analysis dichotomous and continuous variables were calculated using the risk ratio (RR) and standardized mean difference (SMD), respectively. RESULTS: Eight studies involving 987 patients met the criteria for inclusion. The VAS SMD was favoring the experimental group significantly (p < 0.001). Subgroup analysis suggested that the patients performed PVA with mean fracture age less than 3 months would got pain relief earlier and more durable than the control group (P <0.05). The SMD of spinal function assessed with RDQ and Oswestry LBP data was in favor of the experimental groups. QOL outcome improvement was demonstrated statistically significant at early, middle and late term follow-up for PVA than the control group (P <0.05). CONCLUSIONS: In conclusion, this meta-analysis, which evaluated PVA for osteoporotic VCFs, demonstrated significant improvement regarding VAS, spinal function and QOL outcomes. The optimal fracture age was less than 12 weeks. PMID- 26378445 TI - To Share or Not to Share? A Survey of Biomedical Researchers in the U.S. Southwest, an Ethnically Diverse Region. AB - BACKGROUND: Cancer health disparities research depends on access to biospecimens from diverse racial/ethnic populations. This multimethodological study, using mixed methods for quantitative and qualitative analysis of survey results, assessed barriers, concerns, and practices for sharing biospecimens/data among researchers working with biospecimens from minority populations in a 5 state region of the United States (Arizona, Colorado, New Mexico, Oklahoma, and Texas). The ultimate goals of this research were to understand data sharing barriers among biomedical researchers; guide strategies to increase participation in biospecimen research; and strengthen collaborative opportunities among researchers. METHODS AND POPULATION: Email invitations to anonymous participants (n = 605 individuals identified by the NIH RePORT database), resulted in 112 responses. The survey assessed demographics, specimen collection data, and attitudes about virtual biorepositories. Respondents were primarily principal investigators at PhD granting institutions (91.1%) conducting basic (62.3%) research; most were non-Hispanic White (63.4%) and men (60.6%). The low response rate limited the statistical power of the analyses, further the number of respondents for each survey question was variable. RESULTS: Findings from this study identified barriers to biospecimen research, including lack of access to sufficient biospecimens, and limited availability of diverse tissue samples. Many of these barriers can be attributed to poor annotation of biospecimens, and researchers' unwillingness to share existing collections. Addressing these barriers to accessing biospecimens is essential to combating cancer in general and cancer health disparities in particular. This study confirmed researchers' willingness to participate in a virtual biorepository (n = 50 respondents agreed). However, researchers in this region listed clear specifications for establishing and using such a biorepository: specifications related to standardized procedures, funding, and protections of human subjects and intellectual property. The results help guide strategies to increase data sharing behaviors and to increase participation of researchers with multiethnic biospecimen collections in collaborative research endeavors. CONCLUSIONS: Data sharing by researchers is essential to leveraging knowledge and resources needed for the advancement of research on cancer health disparities. Although U.S. funding entities have guidelines for data and resource sharing, future efforts should address researcher preferences in order to promote collaboration to address cancer health disparities. PMID- 26378446 TI - Transcriptome Analysis of Poplar during Leaf Spot Infection with Sphaerulina spp. AB - Diseases of poplar caused by the native fungal pathogen Sphaerulina musiva and related species are of growing concern, particularly with the increasing interest in intensive poplar plantations to meet growing energy demands. Sphaerulina musiva is able to cause infection on leaves, resulting in defoliation and canker formation on stems. To gain a greater understanding of the different responses of poplar species to infection caused by the naturally co-evolved Sphaerulina species, RNA-seq was conducted on leaves of Populus deltoides, P. balsamifera and P. tremuloides infected with S. musiva, S. populicola and a new undescribed species, Ston1, respectively. The experiment was designed to contain the pathogen in a laboratory environment, while replicating disease development in commercial plantations. Following inoculation, trees were monitored for disease symptoms, pathogen growth and host responses. Genes involved in phenylpropanoid, terpenoid and flavonoid biosynthesis were generally upregulated in P. balsamifera and P. tremuloides, while cell wall modification appears to play an important role in the defense of P. deltoides. Poplar defensive genes were expressed early in P. balsamifera and P. tremuloides, but their expression was delayed in P. deltoides, which correlated with the rate of disease symptoms development. Also, severe infection in P. balsamifera led to leaf abscission. This data gives an insight into the large differences in timing and expression of genes between poplar species being attacked by their associated Sphaerulina pathogen. PMID- 26378447 TI - Prevalence of Mental Illness, Cognitive Disability, and Their Overlap among the Homeless in Nagoya, Japan. AB - BACKGROUND: While the prevalence of mental illness or cognitive disability is higher among homeless people than the general population in Western countries, few studies have investigated its prevalence in Japan or other Asian countries. The present study conducted a survey to comprehensively assess prevalence of mental illness, cognitive disability, and their overlap among homeless individuals living in Nagoya, Japan. METHODS: Participants were 114 homeless individuals. Mental illness was diagnosed based on semi-structured interviews conducted by psychiatrists. The Wechsler Adult Intelligence Scale-III (WAIS-III, simplified version) was used to diagnose intellectual/ cognitive disability. RESULTS: Among all participants, 42.1% (95% CI 33.4-51.3%) were diagnosed with a mental illness: 4.4% (95% CI 1.9-9.9%) with schizophrenia or other psychotic disorder, 17.5% (95% CI 11.6-25.6%) with a mood disorder, 2.6% (95% CI 0.9-7.5%) with an anxiety disorder, 14.0% (95% CI 8.8-21.6%) with a substance-related disorder, and 3.5% (95% CI 1.4-8.8%) with a personality disorder. Additionally, 34.2% (95% CI 26.1-43.3%) demonstrated cognitive disability: 20.2% (95% CI 13.8 28.5%) had mild and 14.0% (95% CI 8.8-21.6%) had moderate or severe disability. The percent overlap between mental illness and cognitive disability was 15.8% (95% CI 10.2-23.6%). Only 39.5% (95% CI 26.1-43.3%) of the participants were considered to have no psychological or cognitive dysfunction. Participants were divided into four groups based on the presence or absence of mental illness and/or cognitive disability. Only individuals with a cognitive disability reported a significant tendency toward not wanting to leave their homeless life. CONCLUSION: This is the first report showing that the prevalence of mental illness and/or cognitive disability among homeless individuals is much higher than in the general Japanese population. Appropriate support strategies should be devised and executed based on the specificities of an individual's psychological and cognitive condition. PMID- 26378448 TI - Visual Detection of Human Antibodies Using Sugar Chain-Immobilized Fluorescent Nanoparticles: Application as a Point of Care Diagnostic Tool for Guillain-Barre Syndrome. AB - Sugar chain binding antibodies have gained substantial attention as biomarkers due to their crucial roles in various disorders. In this study, we developed simple and quick detection method of anti-sugar chain antibodies in sera using our previously developed sugar chain-immobilized fluorescent nanoparticles (SFNPs) for the point-of-care diagnostics. Sugar chain structure on SFNPs was modified with the sugar moieties of the GM1 ganglioside via our original linker molecule to detect anti-GM1 antibodies. The structures and densities of the sugar moieties immobilized on the nanoparticles were evaluated in detail using lectins and sera containing anti-GM1 antibodies from patients with Guillain-Barre syndrome, a neurological disorder, as an example of disease involving anti-sugar chain antibodies. When optimized SFNPs were added to sera from patients with Guillain-Barre syndrome, fluorescent aggregates were able to visually detect under UV light in three hours. The sensitivity of the detection method was equivalent to that of the current ELISA method used for the diagnosis of Guillain Barre syndrome. These results suggest that our method using SFNPs is suitable for the point-of-care diagnostics of diseases involving anti-sugar chain antibodies. PMID- 26378449 TI - Gene Expression Ratios Lead to Accurate and Translatable Predictors of DR5 Agonism across Multiple Tumor Lineages. AB - Death Receptor 5 (DR5) agonists demonstrate anti-tumor activity in preclinical models but have yet to demonstrate robust clinical responses. A key limitation may be the lack of patient selection strategies to identify those most likely to respond to treatment. To overcome this limitation, we screened a DR5 agonist Nanobody across >600 cell lines representing 21 tumor lineages and assessed molecular features associated with response. High expression of DR5 and Casp8 were significantly associated with sensitivity, but their expression thresholds were difficult to translate due to low dynamic ranges. To address the translational challenge of establishing thresholds of gene expression, we developed a classifier based on ratios of genes that predicted response across lineages. The ratio classifier outperformed the DR5+Casp8 classifier, as well as standard approaches for feature selection and classification using genes, instead of ratios. This classifier was independently validated using 11 primary patient derived pancreatic xenograft models showing perfect predictions as well as a striking linearity between prediction probability and anti-tumor response. A network analysis of the genes in the ratio classifier captured important biological relationships mediating drug response, specifically identifying key positive and negative regulators of DR5 mediated apoptosis, including DR5, CASP8, BID, cFLIP, XIAP and PEA15. Importantly, the ratio classifier shows translatability across gene expression platforms (from Affymetrix microarrays to RNA-seq) and across model systems (in vitro to in vivo). Our approach of using gene expression ratios presents a robust and novel method for constructing translatable biomarkers of compound response, which can also probe the underlying biology of treatment response. PMID- 26378451 TI - Correction: Npvf: Hypothalamic Biomarker of Ambient Temperature Independent of Nutritional Status. PMID- 26378450 TI - Inhaled Long-Acting beta2-Agonists Do Not Increase Fatal Cardiovascular Adverse Events in COPD: A Meta-Analysis. AB - BACKGROUND: The cardiovascular safety of inhaled long-acting beta2-agonists (LABAs) in patients with chronic obstructive pulmonary disease (COPD) is a controversial problem. Certain studies have suggested that inhaled LABAs lead to an increased risk of cardiovascular events in patients with COPD. This meta analysis aimed to assess the cardiovascular safety of inhaled LABAs in COPD. METHODS: A meta-analysis of randomized, double-blind, parallel-group, placebo controlled trials for LABA treatment of COPD with at least 3 months of follow-up was performed. The fixed-effects model was used to evaluate the effects of LABAs on fatal cardiovascular adverse events. Adverse events were collected for each trial, and the relative risk (RR) and 95% confidence intervals (CI) for LABA/placebo were estimated. RESULTS: There were 24 trials included in this meta analysis. Compared with placebo, inhaled LABAs significantly decreased fatal cardiovascular adverse events in COPD patients (RR 0.65, 95% CI 0.50 to 0.86, P = 0.002). In sensitivity analysis, there was still no increased risk of fatal cardiovascular events (RR 0.68, 95%CI 0.46 to 1.01, P = 0.06) after excluding the trial with the largest weight. Among the different types of LABAs, only salmeterol had a significant effect (RR 0.64, 95% CI 0.46 to 0.90). In subgroup analyses, inhaled LABAs were able to significantly decrease fatal cardiovascular events in long-term trials (RR 0.64, 95% CI 0.47 to 0.87) and in trials with severe COPD patients (RR 0.69, 95% CI 0.50 to 0.96). CONCLUSION: Inhaled LABAs do not increase the risk of fatal cardiovascular events in COPD patients. PMID- 26378452 TI - Comprehensive Serology Based on a Peptide ELISA to Assess the Prevalence of Closely Related Equine Herpesviruses in Zoo and Wild Animals. AB - Equine herpesvirus type 1 (EHV-1) causes respiratory disorders and abortion in equids while EHV-1 regularly causes equine herpesvirus myeloencephalopathy (EHM), a stroke-like syndrome following endothelial cell infection in horses. Both EHV-1 and EHV-9 infections of non-definitive hosts often result in neuronal infection and high case fatality rates. Hence, EHV-1 and EHV-9 are somewhat unusual herpesviruses and lack strict host specificity, and the true extent of their host ranges have remained unclear. In order to determine the seroprevalence of EHV-1 and EHV-9, a sensitive and specific peptide-based ELISA was developed and applied to 428 sera from captive and wild animals representing 30 species in 12 families and five orders. Members of the Equidae, Rhinocerotidae and Bovidae were serologically positive for EHV-1 and EHV-9. The prevalence of EHV-1 in the sampled wild zebra populations was significantly higher than in zoos suggesting captivity may reduce exposure to EHV-1. Furthermore, the seroprevalence for EHV-1 was significantly higher than for EHV-9 in zebras. In contrast, EHV-9 antibody prevalence was high in captive and wild African rhinoceros species suggesting that they may serve as a reservoir or natural host for EHV-9. Thus, EHV-1 and EHV 9 have a broad host range favoring African herbivores and may have acquired novel natural hosts in ecosystems where wild equids are common and are in close contact with other perissodactyls. PMID- 26378454 TI - Correction: Historical Perspective and Risk of Multiple Neglected Tropical Diseases in Coastal Tanzania: Compositional and Contextual Determinants of Disease Risk. PMID- 26378453 TI - Copeptin as an Indicator of Hemodynamic Derangement and Prognosis in Liver Cirrhosis. AB - BACKGROUND: Advanced liver cirrhosis is associated with systemic hemodynamic derangement leading to the development of severe complications associated with increased mortality. Copeptin is a stable cleavage product of the precursor of arginine vasopressin, a key-regulator in hemodynamic homeostasis. Copeptin is currently considered a reliable prognostic marker in a wide variety of diseases other than cirrhosis. The present study aimed to assess copeptin, both experimentally and clinically, as a potential biomarker of hemodynamic derangement and to evaluate its prognostic significance in cirrhosis. MATERIALS AND METHODS: Two studies were executed: 1) in 18 thioacetamide-induced cirrhotic rats and 5 control rats, plasma copeptin and hemodynamic measurements were performed, 2) in 61 cirrhotic patients, serum copeptin concentration was measured in samples collected at time of registration at the waiting list for liver transplantation. In 46 patients, also a second copeptin measurement was performed during follow-up while registered at the waiting list for liver transplantation. To determine the association of serum copeptin and clinical data with outcome, Cox proportional hazard regression analysis and Kaplan Meier analysis were performed. RESULTS: Plasma copeptin concentration was significantly higher in cirrhotic rats than in controls (1.6 +/- 0.5 vs. 0.9 +/- 0.1 pmol/L, p< 0.01) and was negatively correlated to the mean arterial blood pressure (r = -0.574, p = 0.013). In cirrhotic patients, serum copeptin concentration was high [11.0 (5.2 24.0) pmol/L] and increased significantly during the time of registration at the waiting list for liver transplantation. MELD and MELD-sodium score were significantly correlated to serum copeptin [MELD: (r = 0.33, p = 0.01), MELD sodium: (r = 0.29, p = 0.02)], also at time of the second copeptin measurement [MELD and MELD-sodium: r = 0.39, p< 0.01]. In cirrhotic humans, serum copeptin concentration was significantly associated with outcome, independently of the MELD and MELD-sodium score. Patients with a low serum copeptin concentration at time of registration at the liver transplant waiting list had significantly better transplant-free survival rates at 3, 6 and 12 months of follow-up as compared to those with a high serum copeptin concentration (Log-rank: p< 0.01, p< 0.01 and p = 0.02 respectively). CONCLUSIONS: Circulating copeptin levels are elevated in rats and humans with cirrhosis. Copeptin is independently associated with outcome in cirrhotic patients awaiting liver transplantation. PMID- 26378455 TI - Mice Deficient in Proglucagon-Derived Peptides Exhibit Glucose Intolerance on a High-Fat Diet but Are Resistant to Obesity. AB - Homozygous glucagon-GFP knock-in mice (Gcggfp/gfp) lack proglucagon derived peptides including glucagon and GLP-1, and are normoglycemic. We have previously shown that Gcggfp/gfp show improved glucose tolerance with enhanced insulin secretion. Here, we studied glucose and energy metabolism in Gcggfp/gfp mice fed a high-fat diet (HFD). Male Gcggfp/gfp and Gcggfp/+ mice were fed either a normal chow diet (NCD) or an HFD for 15-20 weeks. Regardless of the genotype, mice on an HFD showed glucose intolerance, and Gcggfp/gfp mice on HFD exhibited impaired insulin secretion whereas Gcggfp/+ mice on HFD exhibited increased insulin secretion. A compensatory increase in beta-cell mass was observed in Gcggfp/+mice on HFD, but not in Gcggfp/gfp mice on the same diet. Weight gain was significantly lower in Gcggfp/gfp mice than in Gcggfp/+mice. Oxygen consumption was enhanced in Gcggfp/gfp mice compared to Gcggfp/+ mice on an HFD. HFD feeding significantly increased uncoupling protein 1 mRNA expression in brown adipose and inguinal white adipose tissues of Gcggfp/gfp mice, but not of Gcggfp/+mice. Treatment with the glucagon-like peptide-1 receptor agonist liraglutide (200 mg/kg) improved glucose tolerance in Gcggfp/gfp mice and insulin content in Gcggfp/gfp and Gcggfp/+ mice was similar after liraglutide treatment. Our findings demonstrate that Gcggfp/gfp mice develop diabetes upon HFD-feeding in the absence of proglucagon-derived peptides, although they are resistant to diet induced obesity. PMID- 26378457 TI - PAFit: A Statistical Method for Measuring Preferential Attachment in Temporal Complex Networks. AB - Preferential attachment is a stochastic process that has been proposed to explain certain topological features characteristic of complex networks from diverse domains. The systematic investigation of preferential attachment is an important area of research in network science, not only for the theoretical matter of verifying whether this hypothesized process is operative in real-world networks, but also for the practical insights that follow from knowledge of its functional form. Here we describe a maximum likelihood based estimation method for the measurement of preferential attachment in temporal complex networks. We call the method PAFit, and implement it in an R package of the same name. PAFit constitutes an advance over previous methods primarily because we based it on a nonparametric statistical framework that enables attachment kernel estimation free of any assumptions about its functional form. We show this results in PAFit outperforming the popular methods of Jeong and Newman in Monte Carlo simulations. What is more, we found that the application of PAFit to a publically available Flickr social network dataset yielded clear evidence for a deviation of the attachment kernel from the popularly assumed log-linear form. Independent of our main work, we provide a correction to a consequential error in Newman's original method which had evidently gone unnoticed since its publication over a decade ago. PMID- 26378456 TI - The Genomic Basis of Postponed Senescence in Drosophila melanogaster. AB - Natural populations harbor considerable genetic variation for lifespan. While evolutionary theory provides general explanations for the existence of this variation, our knowledge of the genes harboring naturally occurring polymorphisms affecting lifespan is limited. Here, we assessed the genetic divergence between five Drosophila melanogaster lines selected for postponed senescence for over 170 generations (O lines) and five lines from the same base population maintained at a two week generation interval for over 850 generations (B lines). On average, O lines live 70% longer than B lines, are more productive at all ages, and have delayed senescence for other traits than reproduction. We performed population sequencing of pools of individuals from all B and O lines and identified 6,394 genetically divergent variants in or near 1,928 genes at a false discovery rate of 0.068. A 2.6 Mb region at the tip of the X chromosome contained many variants fixed for alternative alleles in the two populations, suggestive of a hard selective sweep. We also assessed genome wide gene expression of O and B lines at one and five weeks of age using RNA sequencing and identified genes with significant (false discovery rate < 0.05) effects on gene expression with age, population and the age by population interaction, separately for each sex. We identified transcripts that exhibited the transcriptional signature of postponed senescence and integrated the gene expression and genetic divergence data to identify 98 (175) top candidate genes in females (males) affecting postponed senescence and increased lifespan. While several of these genes have been previously associated with Drosophila lifespan, most are novel and constitute a rich resource for future functional validation. PMID- 26378458 TI - Autophosphorylation of the Bacterial Tyrosine-Kinase CpsD Connects Capsule Synthesis with the Cell Cycle in Streptococcus pneumoniae. AB - Bacterial capsular polysaccharides (CPS) are produced by a multi-protein membrane complex, in which a particular type of tyrosine-autokinases named BY-kinases, regulate their polymerization and export. However, our understanding of the role of BY-kinases in these processes remains incomplete. In the human pathogen Streptococcus pneumoniae, the BY-kinase CpsD localizes at the division site and participates in the proper assembly of the capsule. In this study, we show that the cytoplasmic C-terminal end of the transmembrane protein CpsC is required for CpsD autophosphorylation and localization at mid-cell. Importantly, we demonstrate that the CpsC/CpsD complex captures the polysaccharide polymerase CpsH at the division site. Together with the finding that capsule is not produced at the division site in cpsD and cpsC mutants, these data show that CPS production occurs exclusively at mid-cell and is tightly dependent on CpsD interaction with CpsC. Next, we have analyzed the impact of CpsD phosphorylation on CPS production. We show that dephosphorylation of CpsD induces defective capsule production at the septum together with aberrant cell elongation and nucleoid defects. We observe that the cell division protein FtsZ assembles and localizes properly although cell constriction is impaired. DAPI staining together with localization of the histone-like protein HlpA further show that chromosome replication and/or segregation is defective suggesting that CpsD autophosphorylation interferes with these processes thus resulting in cell constriction defects and cell elongation. We show that CpsD shares structural homology with ParA-like ATPases and that it interacts with the chromosome partitioning protein ParB. Total internal reflection fluorescence microscopy imaging demonstrates that CpsD phosphorylation modulates the mobility of ParB. These data support a model in which phosphorylation of CpsD acts as a signaling system coordinating CPS synthesis with chromosome segregation to ensure that daughter cells are properly wrapped in CPS. PMID- 26378459 TI - Cued to Act on Impulse: More Impulsive Choice and Risky Decision Making by Women Susceptible to Overeating after Exposure to Food Stimuli. AB - There is increasing evidence that individual differences in tendency to overeat relate to impulsivity, possibly by increasing reactivity to food-related cues in the environment. This study tested whether acute exposure to food cues enhanced impulsive and risky responses in women classified on tendency to overeat, indexed by scores on the three factor eating questionnaire disinhibition (TFEQ-D), restraint (TFEQ-R) and hunger scales. Ninety six healthy women completed two measures of impulsive responding (delayed discounting, DDT and a Go No-Go, GNG, task) and a measure of risky decision making (the balloon analogue risk task, BART) as well as questionnaire measures of impulsive behaviour either after looking at a series of pictures of food or visually matched controls. Impulsivity (DDT) and risk-taking (BART) were both positively associated with TFEQ-D scores, but in both cases this effect was exacerbated by prior exposure to food cues. No effects of restraint were found. TFEQ-D scores were also related to more commission errors on the GNG, while restrained women were slower on the GNG, but neither effect was modified by cue exposure. Overall these data suggest that exposure to food cues act to enhance general impulsive responding in women at risk of overeating and tentatively suggest an important interaction between tendency for impulsive decision making and food cues that may help explain a key underlying risk factor for overeating. PMID- 26378461 TI - Hydrogen Abstraction Reactions from Phenolic Compounds by Peroxyl Radicals: Multireference Character and Density Functional Theory Rate Constants. AB - An assessment of multireference character in transition states is considered to be an important component in establishing the expected reliability of various electronic structure methods. In the present work, the multireference characters of the transition states and the forming and breaking of bonds for a large set of hydrogen abstraction reactions from phenolic compounds by peroxyl radicals have been analyzed using the T1, M, B1, and GB1 diagnostics. The extent of multireference character depends on the system and on the conditions under which the reaction takes place, and some systematic trends are observed. In particular, the multireference character is found to be reduced by solvation, the size of the phenolic compound, and deprotonation in aqueous solution. However, the deviations of calculated rate constants from experimental ones are not correlated with the extent of multireference character. The performance of single-determinant density functional theory was investigated for the kinetics of these reactions by comparing calculated rate constants to experimental data; the results from these analyses showed that the M05 functional performs well for the task at hand. PMID- 26378460 TI - Interdomain Contacts and the Stability of Serralysin Protease from Serratia marcescens. AB - The serralysin family of bacterial metalloproteases is associated with virulence in multiple modes of infection. These extracellular proteases are members of the Repeats-in-ToXin (RTX) family of toxins and virulence factors, which mediated virulence in E. coli, B. pertussis, and P. aeruginosa, as well as other animal and plant pathogens. The serralysin proteases are structurally dynamic and their folding is regulated by calcium binding to a C-terminal domain that defines the RTX family of proteins. Previous studies have suggested that interactions between N-terminal sequences and this C-terminal domain are important for the high thermal and chemical stabilities of the RTX proteases. Extending from this, stabilization of these interactions in the native structure may lead to hyperstabilization of the folded protein. To test this hypothesis, cysteine pairs were introduced into the N-terminal helix and the RTX domain and protease folding and activity were assessed. Under stringent pH and temperature conditions, the disulfide-bonded mutant showed increased protease activity and stability. This activity was dependent on the redox environment of the refolding reaction and could be blocked by selective modification of the cysteine residues before protease refolding. These data demonstrate that the thermal and chemical stability of these proteases is, in part, mediated by binding between the RTX domain and the N-terminal helix and demonstrate that stabilization of this interaction can further stabilize the active protease, leading to additional pH and thermal tolerance. PMID- 26378462 TI - Matrix-Free UV-Laser Desorption Ionization Mass Spectrometry as a Versatile Approach for Accelerating Dereplication Studies on Lichens. AB - The present study examined the suitability of laser desorption/ionization time-of flight mass spectrometry (LDI-MS) for the rapid chemical fingerprinting of lichen extracts. Lichens are known to produce a wide array of secondary metabolites. Most of these compounds are unique to the symbiotic condition but some can be found in many species. Therefore, dereplication, that is, the rapid identification of known compounds within a complex mixture is crucial in the search for novel natural products. Over the past decade, significant advances were made in analytical techniques and profiling methods specifically adapted to crude lichen extracts, but LDI-MS has never been applied in this context. However, most classes of lichen metabolites have UV chromophores, which are quite similar to commercial matrix molecules used in matrix-assisted laser desorption ionization (MALDI). It is consequently postulated that these molecules could be directly detectable by matrix-free LDI-MS. The present study evaluated the versatility of this technique by investigating the LDI properties of a vast array of single lichen metabolites as well as lichen extracts of known chemical composition. Results from the LDI experiments were compared with those obtained by direct ESI-MS detection as well as LC-ESI-MS. It was shown that LDI ionization leads to strong molecular ion formation with little fragmentation, thus, facilitating straightforward spectra interpretation and representing a valuable alternative to time-consuming LC-MS analysis. PMID- 26378463 TI - Alkynylation of Tertiary Cycloalkanols via Radical C-C Bond Cleavage: A Route to Distal Alkynylated Ketones. AB - An efficient Na2S2O8-promoted radical coupling of tertiary cycloalkanols with alkynyl hypervalent iodide reagents via C-C bond cleavage was developed. This tandem ring-opening/alkynylation procedure showed some advantages, including mild conditions and wide substrate scope, thus providing a simple synthetic method for beta-, gamma- and delta-alkynylated ketones. PMID- 26378464 TI - Kinetically and Crystallographically Guided Mutations of a Benzoate CoA Ligase (BadA) Elucidate Mechanism and Expand Substrate Permissivity. AB - A benzoate CoA ligase (BadA), isolated from the bacterium Rhodopseudomonas palustris, catalyzes the conversion of benzoate to benzoyl CoA on the catabolic pathway of aromatic carboxylic acids. Herein, apparent Michaelis constants K(app)cat and K(app)M were determined for an expanded array of 31 substrates chosen to systematically probe the active site architecture of the enzyme and provide a baseline for expansion of wild-type substrate specificity. Acyl CoA products were observed for 25 of the 31 substrates; in general, BadA converted ortho-substituted substrates better than the corresponding meta and para regioisomers, and the turnover number was more affected by steric rather than electronic effects. The kinetic data are interpreted in relation to six crystal structures of BadA in complex with several substrates and a benzoyl-AMP reaction intermediate. In contrast to other known natural substrate-bound benzoate ligase structures, all substrate-bound BadA structures adopted the thiolation conformation instead of the adenylation conformation. We also observed all the aryl carboxylates to be uniquely oriented within the active site, relative to other structures. Together, the kinetics and structural data suggested a mechanism that involves substrate binding in the thiolation conformation, followed by substrate rotation to an active orientation upon the transition to the adenylation conformation. On the basis of this hypothesis and the structural data, sterically demanding active site residues were mutated, and the substrate specificity was expanded substantially versus that of BadA. Novel activities were seen for substrates with larger substituents, including phenyl acetate. Additionally, the mutant Lys427Ala identified this nonconserved residue as essential for the thiolation step of BadA, but not adenylation. These variously acylated CoAs can serve as novel substrates of acyl CoA-dependent acyltransferases in coupled enzyme assays to produce analogues of bioactive natural products. PMID- 26378465 TI - Robust Mechanical-to-Electrical Energy Conversion from Short-Distance Electrospun Poly(vinylidene fluoride) Fiber Webs. AB - Electrospun polyvinylidene fluoride (PVDF) nanofiber webs have shown great potential in making mechanical-to-electrical energy conversion devices. Previously, polyvinylidene fluoride (PVDF) nanofibers were produced either using near-field electrospinning (spinning distance<1 cm) or conventional electrospinning (spinning distance>8 cm). PVDF fibers produced by an electrospinning at a spinning distance between 1 and 8 cm (referred to as "short distance" electrospinning in this paper) has received little attention. In this study, we have found that PVDF electrospun in such a distance range can still be fibers, although interfiber connection is formed throughout the web. The interconnected PVDF fibers can have a comparable beta crystal phase content and mechanical-to-electrical energy conversion property to those produced by conventional electrospinning. However, the interfiber connection was found to considerably stabilize the fibrous structure during repeated compression and decompression for electrical conversion. More interestingly, the short-distance electrospun PVDF fiber webs have higher delamination resistance and tensile strength than those of PVDF nanofiber webs produced by conventional electrospinning. Short-distance electrospun PVDF nanofibers could be more suitable for the development of robust energy harvesters than conventionally electrospun PVDF nanofibers. PMID- 26378467 TI - Carbon Nanotubes as Reinforcement of Cellulose Liquid Crystalline Responsive Networks. AB - The incorporation of small amount of highly anisotropic nanoparticles into liquid crystalline hydroxypropylcellulose (LC-HPC) matrix improves its response when is exposed to humidity gradients due to an anisotropic increment of order in the structure. Dispersed nanoparticles give rise to faster order/disorder transitions when exposed to moisture as it is qualitatively observed and quantified by stress time measurements. The presence of carbon nanotubes derives in a improvement of the mechanical properties of LC-HPC thin films. PMID- 26378466 TI - Exploiting Expression of Hippo Effector, Yap, for Expansion of Functional Islet Mass. AB - Loss of pancreas beta-cell function is the precipitating factor in all forms of diabetes. Cell replacement therapies, such as islet transplantation, remain the best hope for a cure; however, widespread implementation of this method is hampered by availability of donor tissue. Thus, strategies that expand functional beta-cell mass are crucial for widespread usage in diabetes cell replacement therapy. Here, we investigate the regulation of the Hippo-target protein, Yes associated protein (Yap), during development of the endocrine pancreas and its function after reactivation in human cadaveric islets. Our results demonstrate that Yap expression is extinguished at the mRNA level after neurogenin-3 dependent specification of the pancreas endocrine lineage, correlating with proliferation decreases in these cells. Interestingly, when a constitutively active form of Yap was expressed in human cadaver islets robust increases in proliferation were noted within insulin-producing beta-cells. Importantly, proliferation in these cells occurs without negatively affecting beta-cell differentiation or functional status. Finally, we show that the proproliferative mammalian target of rapamycin pathway is activated after Yap expression, providing at least one explanation for the observed increases in beta-cell proliferation. Together, these results provide a foundation for manipulating Yap activity as a novel approach to expand functional islet mass for diabetes regenerative therapy. PMID- 26378468 TI - Design, Synthesis, and Properties of Phosphoramidate 2',5'-Linked Branched RNA: Toward the Rational Design of Inhibitors of the RNA Lariat Debranching Enzyme. AB - Two RNA fragments linked by means of a 2',5' phosphodiester bridge (2' hydroxyl of one fragment connected to the 5' hydroxyl of the other) constitute a class of nucleic acids known as 2'-5' branched RNAs (bRNAs). In this report we show that bRNA analogues containing 2'-5' phosphoramidate linkages (bN-RNAs) inhibit the lariat debranching enzyme, a 2',5'-phosphodiesterase that has recently been implicated in neurodegenerative diseases associated with aging. bN-RNAs were efficiently generated using automated solid-phase synthesis and suitably protected branchpoint building blocks. Two orthogonally removable groups, namely the 4-monomethoxytrityl (MMTr) group and the fluorenylmethyl-oxycarbonyl (Fmoc) groups, were evaluated as protecting groups of the 2' amino functionality. The 2' N-Fmoc methodology was found to successfully produce bN-RNAs on solid-phase oligonucleotide synthesis. The synthesized bN-RNAs resisted hydrolysis by the lariat debranching enzyme (Dbr1) and, in addition, were shown to attenuate the Dbr1-mediated hydrolysis of native bRNA. PMID- 26378469 TI - Desulfonylative Methenylation of beta-Keto Sulfones. AB - A one-step strategy for the synthesis of alpha-methenyl ketones from beta-keto sufones is reported. Success of the methodology is elaborated for the synthesis of chromanones and isoflavanones in one-step. PMID- 26378470 TI - Application of the Activity Framework for Assessing Aquatic Ecotoxicology Data for Organic Chemicals. AB - Toxicological research in the 1930s gave the first indications of the link between narcotic toxicity and the chemical activity of organic chemicals. More recently, chemical activity has been proposed as a novel exposure parameter that describes the fraction of saturation and that quantifies the potential for partitioning and diffusive uptake. In the present study, more than 2000 acute and chronic algal, aquatic invertebrates and fish toxicity data, as well as water solubility and melting point values, were collected from a series of sources. The data were critically reviewed and grouped by mode of action (MoA). We considered 660 toxicity data to be of acceptable quality. The 328 data which applied to the 72 substances identified as MoA 1 were then evaluated within the activity toxicity framework: EC50 and LC50 values for all three taxa correlated generally well with (subcooled) liquid solubilities. Acute toxicity was typically exerted within the chemical activity range of 0.01-0.1, whereas chronic toxicity was exerted in the range of 0.001-0.01. These results confirm that chemical activity has the potential to contribute to the determination, interpretation and prediction of toxicity to aquatic organisms. It also has the potential to enhance regulation of organic chemicals by linking results from laboratory tests, monitoring and modeling programs. The framework can provide an additional line of evidence for assessing aquatic toxicity, for improving the design of toxicity tests, reducing animal usage and addressing chemical mixtures. PMID- 26378472 TI - Ferroelectric Tunnel Junction for Dense Cross-Point Arrays. AB - Cross-point array (CPA) structure memories using a memristor are attracting a great deal of attention due to their high density integration with a 4F2 cell. However, a common significant drawback of the CPA configuration is crosstalk between cells. To date, the CPA structure using a redox-based memristor has restrictions to minimize the operating current level due to their resistive switching mechanism. This study demonstrates suitable characteristics of a ferroelectric tunnel junction (FTJ) for the memristor of the CPA structure using an electrostatic model. From the FTJ of the Au/p-type Pr0.98Ca0.02MnO3 (4 nm)/BaTiO3 (4.3 nm)/n-type Ca0.98Pr0.02MnO3 (3 nm)/Pt(111) structure, which has a higher and thicker potential barrier, a good memristive effect for the CPA structure with a high nonlinear current-voltage curve and low current operation, was obtained by Delta Fowler-Nordheim tunneling with effectively blocked direct tunneling and thermionic emission. The FTJ demonstrated reduced sneak current and the possible for high nonlinearity. PMID- 26378471 TI - Homoleptic transition metal complexes of the 7-azaindolide ligand featuring kappa(1)-N1 coordination. AB - Homoleptic complexes of the anion of 7-azaindole (AzaIn) were synthesized and characterized for a series of 3d transition metals. For Mn(II), Fe(II), and Co(II), complexes of formula Na2[M(AzaIn)4].2L (L = tetrahydrofuran (THF), 2 MeTHF, toluene, or benzene) were isolated by treatment of the corresponding metal chloride salts with 7-azaindole in the presence of sodium hexamethyldisilazide. The complexes adopt tetrahedral geometries with exclusive coordination to the transition metal ion through the pyrrolic N1 nitrogen atoms of the AzaIn ligands. Solid-state structures of the complexes demonstrate that the sodium cations remain tightly associated with the coordination entities through interaction with both the pyrrolic and pyridine nitrogen atoms of the azaindolide ligands. For Fe(II), replacement of the sodium cations by other alkali metal ions (Li or K) generates new complexes that demonstrate similar coordination geometries to the sodium salts. As a means of comparison, the Fe(II) complex of 4-azaindolide was also investigated. Na2[Fe(4-AzaIn)4].2L adopts a similar solution structure to the 7-azaindolide complexes as judged by NMR spectroscopy and cyclic voltammetry. Density functional theory calculations were performed to investigate the bonding in the 7-azaindolide complexes. Results demonstrate that 7-azaindolide-kappa(1) N1 is a nearly pure sigma donor ligand that features a high degree of ionic character in its bonding to mid 3d transition metal ions. PMID- 26378473 TI - Integration of Shh and Wnt Signaling Pathways Regulating Hematopoiesis. AB - To investigate the spatial and temporal programmed expression of Shh and Wnt members during key stages of definitive hematopoiesis and the possible mechanism of Shh and Wnt signaling pathways regulating the proliferation of hematopoietic progenitor cells (HPCs). Spatial and temporal programmed gene expression of Shh and Wnt signaling during hematopoiesis corresponded with c-kit(+)lin(-) HPCs proliferation. C-kit(+)Lin(-) populations derived from aorta-gonad-mesonephros (AGM) of Balb/c mice at E10.5 with increased expression of Shh and Wnt3a demonstrated a greater potential for proliferation. Additionally, supplementation with soluble Shh N-terminal peptide promoted the proliferation of c-kit(+)Lin(-) populations by activating the Wnt signaling pathway, an effect which was inhibited by blocking Shh signaling. A specific inhibitor of wnt signaling was capable of inhibiting Shh-induced proliferation in a similar manner to shh inhibitor. Our results provide valuable information on Shh and Wnt signaling involved in hematopoiesis and highlight the importance of interaction of Shh and Wnt signaling in regulating HPCs proliferation. PMID- 26378474 TI - Phenotypic Characterization of Insulin-Resistant and Insulin-Sensitive Obesity. AB - CONTEXT: Whereas insulin resistance and obesity coexist, some obese individuals remain insulin sensitive. OBJECTIVE: We examined phenotypic and metabolic factors associated with insulin sensitivity in both muscle and liver in obese individuals. DESIGN AND PARTICIPANTS: Sixty-four nondiabetic obese adults (29 males) underwent hyperinsulinemic (15 and 80 mU/m(2) . min)-euglycemic clamps with deuterated glucose. Top tertile subjects for glucose infusion rate during the high-dose insulin clamp were assigned Musclesen and those in the lower two tertiles were assigned Muscleres. Secondarily, top tertile subjects for endogenous glucose production suppression during the low-dose insulin clamp were deemed Liversen and the remainder Liverres. MAIN OUTCOMES MEASURES: Clinical and laboratory parameters and visceral, subcutaneous, liver, and pancreatic fat were compared. RESULTS: Musclesen and Muscleres had similar body mass index and total fat (P > .16), but Musclesen had lower glycated hemoglobin (P < .001) and systolic (P = .01) and diastolic (P = .03) blood pressure (BP). Despite similar sc fat (P = 1), Musclesen had lower visceral (P < .001) and liver (P < .001) fat. Liversen had lower visceral (P < .01) and liver (P < .01) fat and C-reactive protein (P = .02) than Liverres. When subjects were grouped by both glucose infusion rate during the high-dose insulin clamp and endogenous glucose production suppression, insulin sensitivity at either muscle or liver conferred apparent protection from the adverse metabolic features that characterized subjects insulin resistant at both sites. High-density lipoprotein-cholesterol, 1 hour glucose, systolic BP, and triglycerides explained 54% of the variance in muscle insulin sensitivity. CONCLUSIONS: Obese subjects who were insulin sensitive at muscle and/or liver exhibited favorable metabolic features, including lower BP, liver and visceral adiposity. This study identifies factors associated with, and possibly contributing to, insulin sensitivity in obesity. PMID- 26378475 TI - Ternary Hybrid Material for High-Performance Lithium-Sulfur Battery. AB - The rechargeable lithium-sulfur battery is a promising option for energy storage applications because of its low cost and high energy density. The electrochemical performance of the sulfur cathode, however, is substantially compromised because of fast capacity decay caused by polysulfide dissolution/shuttling and low specific capacity caused by the poor electrical conductivities of the active materials. Herein we demonstrate a novel strategy to address these two problems by designing and synthesizing a carbon nanotube (CNT)/NiFe2O4-S ternary hybrid material structure. In this unique material architecture, each component synergistically serves a specific purpose: The porous CNT network provides fast electron conduction paths and structural stability. The NiFe2O4 nanosheets afford strong binding sites for trapping polysulfide intermediates. The fine S nanoparticles well-distributed on the CNT/NiFe2O4 scaffold facilitate fast Li(+) storage and release for energy delivery. The hybrid material exhibits balanced high performance with respect to specific capacity, rate capability, and cycling stability with outstandingly high Coulombic efficiency. Reversible specific capacities of 1350 and 900 mAh g(-1) are achieved at rates of 0.1 and 1 C respectively, together with an unprecedented cycling stability of ~0.009% capacity decay per cycle over more than 500 cycles. PMID- 26378477 TI - Co-digestion of sewage sludge and dewatered residues from enzymatic hydrolysis of sugar beet pulp. AB - Sugar beet pulp residues (SBPR) from hydrolysis and dewatering of beet pulp were co-digested with municipal sewage sludge (MSS). The highest biogas yields of nearly 512 dm(3)/kg VSfed (volatile solids fed) were achieved for SBPR, treated both as the monosubstrate and as a mixture with MSS (1 : 1 by weight). Simultaneously, the highest methane production of 348 dm(3) CH4/kg VSfed was determined when the sewage sludge was co-digested with 35% SBPR. The analysis of digestate showed that neither ammonia nor volatile fatty acids destabilized the biogas production. IMPLICATIONS: Processing of sugar beet pulp into bioethanol via enzymatic hydrolysis and microbial fermentation has become increasingly attractive. However, in this process, only the liquid fraction derived from hydrolysis is subjected into alcoholic fermentation, whereas the remaining solid fraction needs to be utilized. This study demonstrated that sugar beet pulp residues after bioethanol production can successfully be co-digested with sewage sludge to increase biogas productivity of anaerobic digesters located at wastewater treatment plants. PMID- 26378476 TI - Immune response to Hepatitis B vaccine in patients with celiac disease: A systematic review and meta-analysis. AB - It is debated whether patients with celiac disease (CD) have non-protective antibody responses to HBV vaccination more frequently than non-affected subjects. To perform a literature review and meta-analysis on protective response to HBV vaccination in CD patients. RCTs and observational controlled studies were eligible. Outcome of interest was an anti-HBs (HBsAb) titer >= 10 IU/L after last vaccine dose. Comparative index was rate ratio (RR). Heterogeneity between studies was addressed and funnel plots were analyzed. Meta-regression models were applied to investigate effect size due to study-specific variables. Twelve retrospective studies on a total of 1,447 participants and 4 prospective studies on 184 subjects were selected. The RR was 0.732 (95% C.I.: 0.664-0.808) and 0.777 (95% C.I.: 0.629-0.960) in the prospective and retrospective studies, respectively. The I(2), indicating heterogeneity, was 51.1% in retrospective, 39.8% in prospective studies. Non-protective antibody responses occurred more frequently in patients than controls. Due to limitations in the available studies, additional trials to evaluate post-vaccination HBsAb titer in CD patients are needed. PMID- 26378478 TI - The Bacterial Hydrophobin BslA is a Switchable Ellipsoidal Janus Nanocolloid. AB - BslA is an amphiphilic protein that forms a highly hydrophobic coat around Bacillus subtilis biofilms, shielding the bacterial community from external aqueous solution. It has a unique structure featuring a distinct partition between hydrophilic and hydrophobic surfaces. This surface property is reminiscent of synthesized Janus colloids. By investigating the behavior of BslA variants at water-cyclohexane interfaces through a set of multiscale simulations informed by experimental data, we show that BslA indeed represents a biological example of an ellipsoidal Janus nanoparticle, whose surface interactions are, moreover, readily switchable. BslA contains a local conformational toggle, which controls its global affinity for, and orientation at, water-oil interfaces. This adaptability, together with single-point mutations, enables the fine-tuning of its solvent and interfacial interactions, and suggests that BslA could be a basis for biotechnological applications. PMID- 26378479 TI - Stressful life events, family support and successful ageing in the Biafran War generation. AB - OBJECTIVES: Although the developing countries contribute substantially to the population of the elderly, little is known about ageing in populous countries like Nigeria, particularly the Biafran War generation (BWG). Some of those who witnessed the Biafran War (also known as Nigerian Civil War) as children are well into late adulthood, while the majority of this pre-war/wartime cohort who are in their golden years will enter into later life in less than a decade from now. The aim of the present research was to examine the role of stressful life events and family support in successful ageing of the BWG. METHOD: Data were collected using a self-administered survey completed by 453 members of the BWG who were >=45 years. The survey included measures such as the Successful Ageing Inventory, Life Events Inventory, and family support subscale of Family Dynamics Scale. Hierarchical multiple regression analyses were conducted to test the hypotheses of the study. RESULTS: The three dimensions of stressful life events (health events, interpersonal events and work-related/financial events) had moderate negative relationships with successful ageing. Family support was moderately and positively associated with successful ageing. For the moderation hypotheses, family support was a significant moderator of only the relationship between work related stressful life events and successful ageing, especially for the <65 years subgroup. CONCLUSION: Growing old can be a very positive experience for both the individual and the society. Family support provides social protection for older people, in the face of difficult socio-economic circumstances. PMID- 26378480 TI - Needle Fracture during Endobronchial Ultrasound-guided Transbronchial Needle Aspiration. PMID- 26378482 TI - Portal Cavernoma in the Era of Mesoportal Shunt (Rex) and Liver Transplant in Children. AB - OBJECTIVE: The mesoportal shunt (MPS) and liver transplantation (LT) have changed the scenario of extrahepatic portal vein obstruction (EHPVO) since the MPS, the only "curative" technique, can now be offered in asymptomatic patients and also thrombotic complications of LT have increased the incidence of EHPVO. MATERIAL AND METHODS: A retrospective study of patients undergoing surgery for EHPVO was conducted between 1990 and 2015. An analysis was done for the shunt permeability and clinical evolution over time. RESULTS: Of the 73 children with EHPVO, 39 were operated (12 posttransplant and 27 idiopathic). The median age at surgery was 9.36 years (range, 1.60-17.42 years). The MPS was the technique of choice; it was offered in 21 patients but eventually could be performed in only 18 (9 posttransplant and 9 idiopathic). The results of MPS were better in idiopathic (just one thrombosis successfully converted into mesocaval bypass). In the MPS after LT (n = 9), six shunts are permeable, two became thrombotic (one patient requiring retransplantation), and one late thrombosis occurred and the patient died eventually because of gastrointestinal bleeding. In the remaining patients (21 out of the 39), MPS was not performed because of intrahepatic cavernoma, portal vein hypoplasia, or insufficient length of vascular graft (especially in left lateral segment graft LT, since the portal vein is usually located in the right upper quadrant). They underwent 10 distal splenorenal shunts (DSRS) (1 posttransplant and 9 idiopathic), 5 proximal splenorenal shunts (PSRS) (1/4), 6 mesocaval shunts (1/5), and 1 modified Sugiura procedure. The results with DSRS have been favorable (one thrombosis, converted into mesocaval bypass). In the PSRS no thrombosis was identified and in the mesocaval shunt one early thrombosis occurred. Posttransplantation group had higher risk of shunt thrombosis, regardless of the surgical technique (chi-square, 0.021). The total increase of platelets after 6 months was not different in MPS as compared with other surgical techniques (analysis of variance, 0.110). CONCLUSIONS: The MPS is the technique of choice in EHPVO for idiopathic thrombosis as well as secondary to LT. Not all cases are favorable for MPS, so the surgeon must consider the possibility of alternative techniques for EHPVO. The results in terms of shunt patency are much better in idiopathic cavernoma that posttransplant patients. PMID- 26378483 TI - The Endoscopic Morphological Features of Congenital Posterior Urethral Obstructions in Boys with Refractory Daytime Urinary Incontinence and Nocturnal Enuresis. AB - Purpose This study aims to evaluate the endoscopic morphological features of congenital posterior urethral obstructions in boys with refractory daytime urinary incontinence and/or nocturnal enuresis. Patients and Methods A total of 54 consecutive patients underwent endoscopy and were diagnosed with a posterior urethral valve (PUV) (types 1-4). PUV type 1 was classified as severe, moderate, or mild. A transurethral incision (TUI) was mainly performed for anterior wall lesions of the PUV. Voiding cystourethrography and pressure flow studies (PFS) were performed before and 3 to 4 months after TUI. Clinical symptoms were evaluated 6 months after TUI, and outcomes were assessed according to PFS waveform pattern groups (synergic pattern [SP] and dyssynergic pattern [DP]). Results All patients had PUV type 1 and/or 3 (i.e., n = 34 type 1, 7 type 3, and 13 types 1 and 3). There were severe (n = 1), moderate (n = 21), and mild (n = 25) cases of PUV type 1. According to PFS, SP and DP were present in 43 and 11 patients, respectively. TUI was effective in the SP group and symptoms improved in 77.4 and 69.3% of patients with daytime incontinence and nocturnal enuresis, respectively. Almost no effect was observed in the DP group. A significant decrease in the detrusor pressure was observed at maximum flow rate using PFS in the SP group. Conclusions PUV type 1 encompassed lesions with a spectrum of obstructions ranging from severe to mild, with mild types whose main obstructive lesion existed at the anterior wall of urethra occurring most frequently in boys with refractory daytime urinary incontinence and/or nocturnal enuresis. PMID- 26378484 TI - Effect of N-Acetylserotonin on Intestinal Recovery Following Intestinal Ischemia Reperfusion Injury in a Rat. AB - OBJECTIVE: N-acetylserotonin (NAS) is a naturally occurring chemical intermediate in the biosynthesis of melatonin. Extensive studies in various experimental models have established that treatment with NAS significantly protects heart and kidney injury from ischemia-reperfusion (IR). The purpose of the present study was to examine the effect of NAS on intestinal recovery and enterocyte turnover after intestinal IR injury in rats. METHODS: Male Sprague-Dawley rats were divided into four experimental groups: (1) Sham rats underwent laparotomy, (2) sham-NAS rats underwent laparotomy and were treated with intraperitoneal (IP) NAS (20 mg/kg); (3) IR rats underwent occlusion of both superior mesenteric artery and portal vein for 30 minutes, followed by 48 hours of reperfusion, and (4) IR NAS rats underwent IR and were treated with IP NAS (20 mg/kg) immediately before abdominal closure. Intestinal structural changes, Park injury score, enterocyte proliferation, and enterocyte apoptosis were determined 24 hours following IR. The expression of Bax, Bcl-2, p-ERK, and caspase-3 in the intestinal mucosa was determined using real-time polymerase chain reaction, Western blot, and immunohistochemistry. A nonparametric Kruskal-Wallis analysis of variance test was used for statistical analysis with p less than 0.05 considered statistically significant. RESULTS: Treatment with NAS resulted in a significant increase in mucosal weight in jejunum and ileum, villus height in the ileum, and crypt depth in jejunum and ileum compared with IR animals. IR-NAS rats also had a significantly proliferation rates as well as a lower apoptotic index in jejunum and ileum which was accompanied by higher Bcl-2 levels compared with IR animals. CONCLUSIONS: Treatment with NAS prevents gut mucosal damage and inhibits programmed cell death following intestinal IR in a rat. PMID- 26378485 TI - Evaluation of Antiseptic Use in Pediatric Surgical Units in the United Kingdom Where Is the Evidence Base? AB - Aim Our aim was to conduct a survey of practice regarding skin preparation products for premature neonates (under 32 weeks gestation, below 1.5 kg) in the United Kingdom (UK) pediatric surgical units and to review the evidence on the safety and efficacy of the commonest skin preparation products used. Methods For the survey, following Cambridge University Hospitals NHS Foundation Trust's (Addenbrooke's Hospital) approval, the UK pediatric surgical units were contacted. Each unit was asked for both unit policy and individual consultant preference for skin preparation in infants. A structured literature search was performed using Medline and EMBASE. All study types investigating skin antisepsis with povidone iodine or chlorhexidine in neonates were included. Abstracts and non-English language articles were excluded. Target outcomes related to effectiveness and potential risks of the product. Results A total of 28 pediatric surgical units were surveyed. Overall, 14 units had a standardized policy, with 8 units using Betadine (Purdue Products L.P., Stamford, CT), 4 using alcoholic chlorhexidine, and 2 using aqueous chlorhexidine. A total of 34 articles fulfilled the criteria for inclusion. There is moderate quality evidence to support the efficacy of chlorhexidine over povidone iodine for preoperative skin antisepsis. There is evidence that povidone iodine can be absorbed, causing reactive hypothyroidism. Chlorhexidine can be absorbed but there is no evidence of this being significant. Both alcoholic and aqueous chlorhexidine can cause skin damage, including burns. Conclusion A majority of pediatric surgical units and individual surgeons use Betadine in premature and below 1.5 kg infants despite this being outside the product license. There is no ideal product choice based on current evidence but surgeons must be aware of the inherent risks and benefits of each product. PMID- 26378486 TI - Trauma-Related Altered States of Consciousness (TRASC) and Functional Impairment I: Prospective Study in Acutely Traumatized Persons. AB - A theoretical framework referred to as a 4-D model has been described for classifying posttraumatic stress symptoms into those potentially occurring within normal waking consciousness (NWC) versus those thought to intrinsically exemplify dissociative experiences, specifically, trauma-related altered states of consciousness (TRASC). As a further test of this theoretical distinction, this prospective study evaluated whether TRASC and NWC forms of distress incrementally and prospectively predicted functional impairment at 6 and 12 weeks following presentation at hospital emergency departments in the acute aftermath of traumatic events in 180 persons. Establishing the clinical significance of both TRASC and NWC-distress symptoms, we found that 6-week markers of TRASC and NWC distress independently predicted 12-week self-reported levels of social and occupational impairment. We also observed broad support for various predictions of the 4-D model except that, in contrast with hypotheses, childhood trauma history was generally more strongly correlated with symptoms of NWC-distress than with TRASC. Future research directions are discussed. PMID- 26378487 TI - Birth weight-related percentiles of brain ventricular system as a tool for assessment of posthemorrhagic hydrocephalus and ventricular enlargement. AB - Besides remarkable improvements of neonatal medical therapy, neurological morbidity remains a major concern in preterm infants. In particular, intracranial hemorrhage is a severe complication strongly correlated to poor neurological outcome. For early clinical assessment of intracranial hemorrhage and its impact on the ventricular system, cranial sonography is an important bedside diagnostic tool. Reference values of ventricular sizes are available in relation to gestational age (GA). So far, it has not been demonstrated that ventricular size values are also reliable in relation to birth weight (BW). In this study, we performed cranial ultrasonography in 250 preterm and term newborn infants. Measurements of the intracranial ventricular system by cranial ultrasound examination were performed within 72 h after birth. We determined ventricular index, anterior horn width, width of the third ventricle, width and length of the fourth ventricle for statistical analysis in relation to BW and GA. GA ranged from 23 weeks, 3 days to 42 weeks, 1 day (mean: 33 weeks), BW ranged from 345 to 5620 g (mean: 2146 g). Ventricular index and fourth ventricle width revealed a significant correlation to birth weight with r=0.75, each. A significant correlation to birth weight was also obtained for width and length of the third ventricle (r=0.55 and 0.47, respectively). Correlations obtained for ventricular measures in relation to GA were similar to those referring to BW. In preterm and term infants, ventricular sizes in relation to BW seem reliable for assessment and monitoring of ventricular pathologies, i.e. after intracranial hemorrhage. PMID- 26378488 TI - Anti-hyperalgesic and anti-nociceptive potentials of standardized grape seed proanthocyanidin extract against CCI-induced neuropathic pain in rats. AB - BACKGROUND: Neuropathic pain is associated with severe chronic sensory disturbances characterized by spontaneous pain, increased responsiveness to painful stimuli (hyperalgesia) and pain perceived in response to non-noxious stimuli (allodynia). Morphine is effective treatment for neuropathic pain but produces tolerance on chronic use. The present study was designed to explore the anti-nociceptive and anti-hyperalgesic effect of grape seed extract using sciatic nerve ligation-induced neuropathic pain in rats. METHODS: Chronic constructive injury (CCI) was performed under anesthesia, on one side leg exposed by making a skin incision, and chromic gut ligatures were tied loosely around the sciatic nerve at 1 mm intervals. The treatment with grape seed proanthocyanidin extract (GSPE) (100 and 200 mg/kg, p.o.) was initiated on 7th day post-surgery and continued for next 14 days. Morphine (10 mg/kg, s.c.) alone and morphine in combination with GSPE (100 mg/kg, p.o.) were administered in CCI rats for 5 days starting from 7th day. On 3rd, 7th, 14th and 21st day, behavioral parameters (mechanical allodynia and thermal hyperalgesia) were assessed. Then the animals were killed on 22nd day and biochemical parameters [reduced glutathione (GSH), lipid peroxidation (LPO), catalase, nitrite, superoxide dismutase (SOD)] were assessed. RESULTS: Ligation of the sciatic nerve significantly induced mechanical allodynia and thermal hyperalgesia and induces oxidative stress (increase in LPO and nitrite) and decline of anti-oxidant enzyme levels (catalase, SOD, GSH) in sciatic nerve homogenate. GSPE (100 and 200 mg/kg, p.o.) attenuated all the behavioural and biochemical parameters. Morphine also significantly reversed the symptoms of neuropathic pain but produced tolerance after 5 days. Further, co treatment of GSPE (100 mg/kg) with morphine (10 mg/kg, s.c.) in CCI rats significantly reversed the morphine tolerance and enhanced its anti-hyperalgesic effect as compared to the morphine-alone-treated group. CONCLUSIONS: In the present set of experiments, GSPE showed a significant anti-hyperalgesic and anti nociceptive effect in rats. PMID- 26378489 TI - Prospective PET image quality gain calculation method by optimizing detector parameters. AB - BACKGROUND: Lutetium-based scintillators with high-performance electronics introduced time-of-flight (TOF) reconstruction in the clinical setting. Let G' be the total signal to noise ratio gain in a reconstructed image using the TOF kernel compared with conventional reconstruction modes. G' is then the product of G1 gain arising from the reconstruction process itself and (n-1) other gain factors (G2, G3, ... Gn) arising from the inherent properties of the detector. METHODS: We calculated G2 and G3 gains resulting from the optimization of the coincidence and energy window width for prompts and singles, respectively. Both quantitative and image-based validated Monte Carlo models of Lu2SiO5 (LSO) TOF permitting and Bi4Ge3O12 (BGO) TOF-nonpermitting detectors were used for the calculations. RESULTS: G2 and G3 values were 1.05 and 1.08 for the BGO detector and G3 was 1.07 for the LSO. A value of almost unity for G2 of the LSO detector indicated a nonsignificant optimization by altering the energy window setting. G' was found to be ~1.4 times higher for the TOF-permitting detector after reconstruction and optimization of the coincidence and energy windows. CONCLUSION: The method described could potentially predict image noise variations by altering detector acquisition parameters. It could also further contribute toward a long-lasting debate related to cost-efficiency issues of TOF scanners versus the non-TOF ones. Some vendors re-engage nowadays to non-TOF product line designs in an effort to reduce crystal costs. Therefore, exploring the limits of image quality gain by altering the parameters of these detectors remains a topical issue. PMID- 26378490 TI - Optimizing an 18F-NaF and 18F-FDG cocktail for PET assessment of metastatic castration-resistant prostate cancer. AB - BACKGROUND: PET/computed tomography (CT) imaging with the sodium-(F)-fluoride/2 (F)-fluoro-2-deoxy-D-glucose (F-NaF/F-FDG) cocktail has been proposed for patients with osseous metastases. This work aimed to optimize the cocktail composition for patients with metastatic castration-resistant prostate cancer (mCRPC). MATERIALS AND METHODS: The study was carried out on six patients with mCRPC, with a total of 26 analyzed lesions. The patients were injected with F-NaF and F-FDG at separate time points. Dynamic PET/CT imaging recorded the uptake time course for both the tracers into osseous metastases. F-NaF and F-FDG uptakes were decoupled by kinetic analysis, which enabled calculation of F-NaF and F-FDG standardized uptake values (SUVs) images. Peak, mean, and total SUVs were evaluated for both tracers and all visible lesions. The F-NaF/F-FDG cocktail was optimized under the assumption that the contribution of both tracers to image formation is equal. SUV images from PET/CT imaging with a combination of F-NaF and F-FDG were generated for cocktail compositions with an F-NaF : F-FDG ratio varying from 1 : 8 to 1 : 2. RESULTS: The F-NaF peak and mean SUVs were on average four to five times higher than the F-FDG peak and mean SUVs, with an interlesion coefficient of variations of 20%. The total SUV for F-NaF was on average seven times higher than that for F-FDG. When the F-NaF : F-FDG ratio changed from 1 : 8 to 1 : 2, the typical SUV on the generated PET images increased by 50%, whereas the change in the uptake visual pattern was hardly noticeable. CONCLUSION: F-NaF and F-FDG in the cocktail contribute equally to image formation when the F-NaF : F-FDG ratio is 1 : 5. Therefore, we propose this ratio as the optimal cocktail composition for mCRPC patients. We also urge to strictly control the cocktail composition during any F-NaF/F-FDG cocktail PET/CT examination. PMID- 26378491 TI - Malignant pheochromocytoma in the elderly: which is the best management in clinical practice? PMID- 26378492 TI - Determinants of Physical Activity Guideline Attainment in Australian Cardiac Patients: A 12-Month Study. AB - PURPOSE: Little is known about the type and intensity of physical activity (PA) reported by cardiac patients during the first year after hospitalization and whether patients are meeting recommended PA guidelines. In addition, the achievement of PA guideline over the course of recovery is largely unknown. METHODS: A total of 136 patients consecutively admitted to 2 Australian hospitals after acute myocardial infarction (31%), or to undergo bypass surgery (29%) or percutaneous coronary intervention (40%), were interviewed at 6 weeks and at 4 and 12 months after admission. Physical activity at each time point was assessed by the Active Australia PA Survey. Medical and sociodemographic data, self reported anxiety and depression, and cardiac rehabilitation attendance status were also recorded. Logistic regression was used to identify predictors of PA guideline attainment at each of the 3 time points. RESULTS: At all 3 time points, walking was regularly performed by more than 95% of patients, while moderate- and vigorous-intensity PA reached only 40% and 59% participation by 12 months, respectively. Significant predictors of PA guideline attainment at 6 weeks posthospitalization were physical functioning, depression, and mode of PA. As hypothesized, different predictors were found at 4 months (living arrangements, PA mode, and attainment of 6-week PA guidelines) and 12 months (living arrangements, socioeconomic resources, PA mode, and attainment of 6-week PA guidelines). CONCLUSIONS: The study highlighted the potential importance of modifying walking behavior in cardiac patients to achieve PA guidelines and the dynamic nature of variables influencing PA at various stages of recovery. PMID- 26378493 TI - The Association Between Insomnia Symptoms and Mood Changes During Exercise Among Patients Enrolled in Cardiac Rehabilitation. AB - PURPOSE: Insomnia symptoms (ie, difficulty falling asleep, difficulty staying asleep, and early awakenings) are common among patients with cardiovascular disease and may interfere with the beneficial impact of exercise on mood state. This study investigated the association of insomnia symptom severity with mood disturbance and with changes in mood state during exercise in a cardiac rehabilitation (CR) population. METHODS: Insomnia symptom severity was measured using the Insomnia Severity Index upon admission to a 12-week CR program (n = 57). The Physical Activity Affect Scale was administered before and during a single bout of moderate intensity exercise to measure changes in mood state. Indices of mood disturbance included depressive symptoms (Hospital Anxiety and Depression Scale) and pre-exercise mood state (Physical Activity Affect Scale). RESULTS: Greater severity of insomnia symptoms was associated with less pleasant mood overall (r = -0.45, P < .001), including less tranquility (r = -0.37, P = .005), lower positive affect (r = -0.39, P = .003), and worse fatigue (r = 0.36, P = .005); greater insomnia symptom severity also predicted greater improvements during exercise in both overall mood state (b = 0.26, standard error = 0.10, P = .009) and tranquility (b = 0.09, standard error = 0.04, P = .04), following statistical adjustment for demographic variables and pre-exercise mood state. CONCLUSIONS: Although CR patients reporting insomnia symptoms tend to experience daytime mood disturbance, they may benefit from mood-elevating properties of exercise. Future research is needed to help optimize mood during exercise, which may have implications for improving psychological distress and CR adherence. PMID- 26378494 TI - Air Pollution and Exercise: A REVIEW OF THE CARDIOVASCULAR IMPLICATIONS FOR HEALTH CARE PROFESSIONALS. AB - Although regular aerobic exercise improves overall health, increased physical activity can lead to heightened exposures to a variety of air pollutants. As such, the cardiovascular health benefits of exercise may be abrogated to some degree by the harmful actions of inhaled pollutants. This review aims to provide an up-to-date summary for health professionals of the cardiovascular responses as well as the risks of exercising in air pollution. Aerobic exercise augments the overall inhaled air pollution dose, potentiates the diffusion of pollutants into circulating blood, and augments oxidative stress and inflammation. The inhalation of particulate matter during exercise can raise blood pressure, impair vascular function, and unfavorably affect autonomic balance. Several studies suggest that air pollutants can increase ischemic symptoms and signs during exercise and can even be capable of impairing exercise performance in some scenarios. The overall evidence supports that the risk-to-benefit ratio generally favors that health care providers continue to strongly encourage their patients to perform regular aerobic exercise. Nevertheless, a greater effort should be made to educate patients about the risks of air pollutant exposures during exercise, particularly those at heightened cardiovascular risk. Although no strategy has been directly tested to reduce morbidity and mortality rate, several prudent actions can be taken to lessen the degree of exposures during exercise which may thereby help mitigate the adverse effects of air pollutants on exercise performance and cardiovascular risk. PMID- 26378495 TI - Hand-Portable Gradient Capillary Liquid Chromatography Pumping System. AB - In this work, a novel splitless nanoflow gradient generator integrated with a stop-flow injector was developed and evaluated using an on-column UV-absorption detector. The gradient pumping system consisted of two nanoflow pumps controlled by micro stepper motors, a mixer connected to a serpentine tube, and a high pressure valve. The gradient system weighed only 4 kg (9 lbs) and could generate up to 55 MPa (8000 psi) pressure. The system could operate using a 24 V DC battery and required 1.2 A for operation. The total volume capacity of the pump was 74 MUL, and a sample volume of 60 nL could be injected. The system provided accurate nanoflow rates as low as 10 nL/min without employing a splitter, making it ideal for capillary column use. The gradient dwell volume was calculated to be 1.3 MUL, which created a delay of approximately 4 min with a typical flow rate of 350 nL/min. Gradient performance was evaluated for gradient step accuracy, and excellent reproducibility was obtained in day-to-day experiments (RSD < 1.2%, n = 4). Linear gradient reproducibility was tested by separating a three-component pesticide mixture on a poly(ethylene glycol) diacrylate (PEGDA) monolithic column. The retention time reproducibility was very good in run-to-run experiments (RSD < 1.42%, n = 4). Finally, excellent separation of five phenols was demonstrated using the nanoflow gradient system. PMID- 26378497 TI - Opposing effects of bile acids deoxycholic acid and ursodeoxycholic acid on signal transduction pathways in oesophageal cancer cells. AB - Ursodeoxycholic acid (UDCA) was reported to reduce bile acid toxicity, but the mechanisms underlying its cytoprotective effects are not fully understood. The aim of the present study was to examine the effects of UDCA on the modulation of deoxycholic acid (DCA)-induced signal transduction in oesophageal cancer cells. Nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1) activity was assessed using a gel shift assay. NF-kappaB activation and translocation was performed using an ELISA-based assay and immunofluorescence analysis. COX-2 expression was analysed by western blotting and COX-2 promoter activity was assessed by luciferase assay. DCA induced NF-kappaB and AP-1 DNA-binding activities in SKGT-4 and OE33 cells. UDCA pretreatment inhibited DCA-induced NF kappaB and AP-1 activation and NF-kappaB translocation. This inhibitory effect was coupled with a blockade of IkappaB-alpha degradation and inhibition of phosphorylation of IKK-alpha/beta and ERK1/2. Moreover, UDCA pretreatment inhibited COX-2 upregulation. Using transient transfection of the COX-2 promoter, UDCA pretreatment abrogated DCA-induced COX-2 promoter activation. In addition, UDCA protected oesophageal cells from the apoptotic effects of deoxycholate. Our findings indicate that UDCA inhibits DCA-induced signalling pathways in oesophageal cancer cells. These data indicate a possible mechanistic role for the chemopreventive actions of UDCA in oesophageal carcinogenesis. PMID- 26378496 TI - Detection and isolation of circulating exosomes and microvesicles for cancer monitoring and diagnostics using micro-/nano-based devices. AB - In the last several years, nanoscale vesicles that originate from tumor cells and which can be found circulating in the blood (i.e. exosomes and microvesicles) have been discovered to contain a wealth of proteomic and genetic information to monitor cancer progression, metastasis, and drug efficacy. However, the use of exosomes and microvesicles as biomarkers to improve patient care has been limited by their small size (30 nm-1 MUm) and the extensive sample preparation required for their isolation and measurement. In this Critical Review, we explore the emerging use of micro and nano-technology to isolate and detect exosomes and microvesicles in clinical samples and the application of this technology to the monitoring and diagnosis of cancer. PMID- 26378498 TI - Cigarette smoke effects on TSPO and VDAC expression in a cellular lung cancer model. AB - As redox iron and copper ions are found in lung pleural fluid and parenchyma, we aimed to examine the effect of cigarette smoke (CS) alone and the combined effects of CS and redox metals, iron and copper ions, containing medium (saliva), on epithelial H1299 lung cancer cells. We also examined the expression levels of the anticarcinogenic and proapoptotic 18 kDa translocator protein (TSPO) and its closely associated protein voltage-dependent anion channel (VDAC). H1299 cells were subjected to western blot analysis using anti-TSPO and anti-VDAC antibodies. With the former, the 18 kDa band appeared as expected and a 72 kDa band also appeared. It may be assumed that in H1299 lung cancer cells, an additional form of TSPO protein appears as a four-unit tetrameric complex, which is affected by CS exposure. A significant decrease in the expression level of the 72 kDa protein occurred following only 60 min of CS exposure, whereas VDAC protein levels were increased following only 30 min of CS exposure. These results, together with our previous related studies, suggest a comprehensive two-arm novel paradigm for lung cancer induced by CS, and mediated by an altered TSPO protein, possibly resulting from both the 72 kDa TSPO degradation and redox metal ion-induced enhancement of free radical attack. We suggest that both of the most important proapoptotic and anticancer proteins, p53 and TSPO, are damaged by CS, paving the way for lung cancer initiation and progression. PMID- 26378499 TI - Prediction of the Standard Gibbs Energy of Transfer of Organic Ions Across the Interface between Two Immiscible Liquids. AB - The non-Bornian solvation model was applied for evaluation of the standard Gibbs energy (DeltaGtr degrees ,W->O) of transfer of organic ions from water (W) to organic solvent (O = nitrobenzene). The solvation energy of an ion in either W or O is basically formulated as the energy required for the formation of a nanosized ion-solvent interface around the ion; however, many organic ions with strongly charged groups (e.g., -SO3-, -CO2-, -NH3+) are preferentially hydrated in O. Here we divided the surface of an ion into "hydrated" and "non-hydrated" surfaces and then carried out regression analyses with experimental values of DeltaGtr degrees ,W->O. In the analyses, the local electric field on the surface of an organic ion was evaluated through density functional theory calculation. Good regression results were then obtained with the mean absolute error of 1.9 and 2.4 kJ mol-1 for 34 anions and 63 cations, respectively. These errors correspond to the error of ~20 mV in the standard ion-transfer potential (DeltaOWphi degrees ), being only two times larger than the typical experimental error (~10 mV) in the voltammetric measurement. This non-Bornian model is promising for theoretical prediction of DeltaGtr degrees ,W->O (or DeltaOWphi degrees ) for organic ions and possibly of the biomembrane permeability for ionic drugs. PMID- 26378500 TI - Simple adaptive sparse representation based classification schemes for EEG based brain-computer interface applications. AB - One of the main problems related to electroencephalogram (EEG) based brain computer interface (BCI) systems is the non-stationarity of the underlying EEG signals. This results in the deterioration of the classification performance during experimental sessions. Therefore, adaptive classification techniques are required for EEG based BCI applications. In this paper, we propose simple adaptive sparse representation based classification (SRC) schemes. Supervised and unsupervised dictionary update techniques for new test data and a dictionary modification method by using the incoherence measure of the training data are investigated. The proposed methods are very simple and additional computation for the re-training of the classifier is not needed. The proposed adaptive SRC schemes are evaluated using two BCI experimental datasets. The proposed methods are assessed by comparing classification results with the conventional SRC and other adaptive classification methods. On the basis of the results, we find that the proposed adaptive schemes show relatively improved classification accuracy as compared to conventional methods without requiring additional computation. PMID- 26378501 TI - Tissue prolapse and stresses in stented coronary arteries: A computer model for multi-layer atherosclerotic plaque. AB - Among the many factors influencing the effectiveness of cardiovascular stents, tissue prolapse indicates the potential of a stent to cause restenosis. The deflection of the arterial wall between the struts of the stent and the tissue is known as a prolapse or draping. The prolapse is associated with injury and damage to the vessel wall due to the high stresses generated around the stent when it expands. The current study investigates the impact of stenosis severity and plaque morphology on prolapse in stented coronary arteries. A finite element method is applied for the stent, plaque, and artery set to quantify the tissue prolapse and the corresponding stresses in stenosed coronary arteries. The variable size of atherosclerotic plaques is considered. A plaque is modelled as a multi-layered medium with different thicknesses attached to the single layer of an arterial wall. The results reveal that the tissue prolapse is influenced by the degree of stenosis severity and the thickness of the plaque layers. Stresses are observed to be significantly different between the plaque layers and the arterial wall tissue. Higher stresses are concentrated in fibrosis layer of the plaque (the harder core), while lower stresses are observed in necrotic core (the softer core) and the arterial wall layer. Moreover, the morphology of the plaque regulates the magnitude and distribution of the stress. The fibrous cap between the necrotic core and the endothelium constitutes the most influential layer to alter the stresses. In addition, the thickness of the necrotic core and the stenosis severity affect the stresses. This study reveals that the morphology of atherosclerotic plaques needs to be considered a key parameter in designing coronary stents. PMID- 26378502 TI - Automated lesion detectors in retinal fundus images. AB - Diabetic retinopathy (DR) is a sight-threatening condition occurring in persons with diabetes, which causes progressive damage to the retina. The early detection and diagnosis of DR is vital for saving the vision of diabetic persons. The early signs of DR which appear on the surface of the retina are the dark lesions such as microaneurysms (MAs) and hemorrhages (HEMs), and bright lesions (BLs) such as exudates. In this paper, we propose a novel automated system for the detection and diagnosis of these retinal lesions by processing retinal fundus images. We devise appropriate binary classifiers for these three different types of lesions. Some novel contextual/numerical features are derived, for each lesion type, depending on its inherent properties. This is performed by analysing several wavelet bands (resulting from the isotropic undecimated wavelet transform decomposition of the retinal image green channel) and by using an appropriate combination of Hessian multiscale analysis, variational segmentation and cartoon+texture decomposition. The proposed methodology has been validated on several medical datasets, with a total of 45,770 images, using standard performance measures such as sensitivity and specificity. The individual performance, per frame, of the MA detector is 93% sensitivity and 89% specificity, of the HEM detector is 86% sensitivity and 90% specificity, and of the BL detector is 90% sensitivity and 97% specificity. Regarding the collective performance of these binary detectors, as an automated screening system for DR (meaning that a patient is considered to have DR if it is a positive patient for at least one of the detectors) it achieves an average 95-100% of sensitivity and 70% of specificity at a per patient basis. Furthermore, evaluation conducted on publicly available datasets, for comparison with other existing techniques, shows the promising potential of the proposed detectors. PMID- 26378503 TI - Synthesis and Pharmacochemistry of New Pleiotropic Pyrrolyl Derivatives. AB - Within the framework of our attempts to synthesize pleiotropic anti-inflammatory agents, we have synthesized some chalcones and their corresponding 3,4-pyrrolyl derivatives. Chalcones constitute a class of compounds with high biological impact. They are known for a number of biological activities, including anti inflammatory and free radical scavenging activities. They inhibit several enzymes implicated in the inflammatory process, such as lipoxygenase, cyclooxygenase (COX) and lysozymes. The synthesized pyrroles have been studied for: (1) their in vitro inhibition of lipoxygenase; (2) their in vitro inhibition of COX; (3) their in vitro inhibition of lipid peroxidation; (4) their interaction with the stable, N-centered, free radical, 2,2-diphenyl-1-picrylhydrazyl (DPPH); (5) their inhibition on interleukin-6 (IL-6); (6) their anti-proteolytic activity; and (7) their in vivo anti-inflammatory activity using carrageenan-induced rat paw edema. Their physicochemical properties were determined to explain the biological results. Lipophilicity was experimentally determined. 2i and 2v were found to be promising multifunctional molecules with high antiproteolytic and anti inflammatory activities in combination with anti-interleukin-6 activity. PMID- 26378504 TI - Separation and Identification of Four New Compounds with Antibacterial Activity from Portulaca oleracea L. AB - The Portulaca oleracea L. (P. oleracea) has been used to treat bacillary dysentery for thousands of years in China. Pharmacology studies on P. oleracea have also showed its significant antibacterial effects on the enteropathogenic bacteria, which might reveal the treatment of P. oleracea in cases of bacillary dysentery to some extent. To date, however, the therapeutic basis of P. oleracea treating on bacillary dysentery remains unknown. We determined the antibacterial effective fraction of P. oleracea in a previous study. The current study, which is based on our previous study, was first designed to isolate, identify and screen antibacterial active constituents from P. oleracea. As a result, four new compounds (1-4), portulacerebroside B (1), portulacerebroside C (2), portulacerebroside D (3) and portulaceramide A (4) along with five known compounds (5-9) were isolated, and structures were established by their physico chemical constants and spectroscopic analysis. The antibacterial activities against common enteropathogenic bacteria were evaluated for all compounds and the new compounds 1-4 showed significant antibacterial effect on enteropathogenic bacteria in vitro, which might contribute to revealing the treatment of P. oleracea in cases of bacillary dysentery. PMID- 26378505 TI - Gallic Acid Is the Major Active Component of Cortex Moutan in Inhibiting Immune Maturation of Human Monocyte-Derived Dendritic Cells. AB - Atopic dermatitis (AD) is a widely prevalent and chronically relapsing inflammatory skin disease. Penta Herbs Formula (PHF) is efficacious in improving the quality of life and reducing topical corticosteroid used in children with AD and one of the active herbs it contains is Cortex Moutan. Recent studies showed that altered functions of dendritic cells (DC) were observed in atopic individuals, suggesting that DC might play a major role in the generation and maintenance of inflammation by their production of pro-inflammatory cytokines. Hence, the aims of the present study were to identify the major active component(s) of Cortex Moutan, which might inhibit DC functions and to investigate their possible interactions with conventional corticosteroid on inhibiting the development of DC from monocytes. Monocyte-derived dendritic cells (moDC) culture model coupled with the high-speed counter-current chromatography (HSCCC), high pressure liquid chromatography (HPLC) and Liquid Chromatography Mass Spectrometry (LCMS) analyses were used. Gallic acid was the major active component from Cortex Moutan which could dose dependently inhibit interleukin (IL)-12 p40 and the functional cluster of differentiation (CD) surface markers CD40, CD80, CD83 and CD86 expression from cytokine cocktail-activated moDC. Gallic acid could also lower the concentration of hydrocortisone required to inhibit the activation of DC. PMID- 26378506 TI - Investigating the Dissolution Performance of Amorphous Solid Dispersions Using Magnetic Resonance Imaging and Proton NMR. AB - We have investigated the dissolution performance of amorphous solid dispersions of poorly water-soluble bicalutamide in a Kollidon VA64 polymeric matrix as a function of the drug loading (5% vs. 30% bicalutamide). A combined suite of state of-the-art analytical techniques were employed to obtain a clear picture of the drug release, including an integrated magnetic resonance imaging UV-Vis flow cell system and 1H-NMR. Off-line 1H-NMR was used for the first time to simultaneously measure the dissolution profiles and rates of both the drug and the polymer from a solid dispersion. MRI and 1H-NMR data showed that the 5% drug loading compact erodes linearly, and that bicalutamide and Kollidon VA64 are released at approximately the same rate from the molecular dispersion. For the 30% extrudate, data indicated a slower water ingress into the compact which corresponds to a slower dissolution rate of both bicalutamide and Kollidon VA64. PMID- 26378507 TI - Synthesis, Antibacterial and Antitubercular Activities of Some 5H-Thiazolo[3,2 a]pyrimidin-5-ones and Sulfonic Acid Derivatives. AB - A series of 5H-thiazolo[3,2-a]pyrimidin-5-ones were synthesized by the cyclization reactions of S-alkylated derivatives in concentrated H2SO4. Upon treatment of S-alkylated derivatives at different temperatures, intramolecular cyclization to 7-(substituted phenylamino)-5H-thiazolo[3,2-a]pyrimidin-5-ones or sulfonation of cyclized products to sulfonic acid derivatives occurred. The structures of the target compounds were confirmed by IR, 1H-NMR, (13)C-NMR and HRMS studies. The compounds were evaluated for their preliminary in vitro antibacterial activity against some Gram-positive and Gram-negative bacteria and screened for antitubercular activity against Mycobacterium tuberculosis by the broth dilution assay method. Some compounds showed good antibacterial and antitubercular activities. PMID- 26378508 TI - Small Molecule Targeting of Protein-Protein Interactions through Allosteric Modulation of Dynamics. AB - The protein-protein interaction (PPI) target class is particularly challenging, but offers potential for "first in class" therapies. Most known PPI small molecules are orthosteric inhibitors but many PPI sites may be fundamentally intractable to this approach. One potential alternative is to consider more attractive, remote small molecule pockets; however, on the whole, allostery is poorly understood and difficult to discover and develop. Here we review the literature in order to understand the basis for allostery, especially as it can apply to PPIs. We suggest that the upfront generation of sophisticated and experimentally validated dynamic models of target proteins can aid in target choice and strategy for allosteric intervention to produce the required functional effect. PMID- 26378509 TI - Synthesis and Evaluation of a Rationally Designed Click-Based Library for G Quadruplex Selective DNA Photocleavage. AB - DNA containing repeating G-rich sequences can adopt higher-order structures known as G-quadruplexes (G4). These structures are believed to form within telomeres and the promoter regions of some genes, particularly in a number of proto oncogenes, where they may play a role in regulating transcription. Alternatively, G4 DNA may act as a barrier to replication. To investigate these potential biological roles, probes that combine highly selective G4 DNA targeting with photocleavage activity can allow temporal detection of G4 DNA, providing opportunities to obtain novel insights about the biological roles of G4 DNA. We have designed, synthesized, and screened a small library of potential selective G quadruplex DNA photocleavage agents incorporating the G-quadruplex targeting moiety of 360A with known photocleavage groups linked via "click" chemistry. PMID- 26378510 TI - Identification of Cultured and Natural Astragalus Root Based on Monosaccharide Mapping. AB - As the main substances responsible for immunomodulatory activity, saccharides can be used as quality indicators for Astragalus root (RA). Saccharide content is commonly determined by ultraviolet spectroscopy, which lacks species specificity and has not been applied in the Chinese Pharmacopoeia. Monosaccharide mapping based on trifluoroacetic acid (TFA) hydrolysis can be used for quantitative analysis of saccharide compositions. In addition, species specificity can be evaluated by analysis of the mapping characteristics. In this study, monosaccharide mapping of soluble saccharides in the cytoplasm and polysaccharides in the cell wall of 24 batches of RA samples with different growth patterns were obtained based on TFA hydrolysis followed by gas chromatography-mass spectrometry. Results indicated that the mapping and the molar ratios of saccharide compositions of the cultured and natural RA samples were different for both cytoplasm and cell wall. For example, the molar ratio of mannose and arabinose was more than 3.5:1 in cytoplasm in cultured RA, whereas the ratio was less than 3.5:1 in natural RA. This research not only lays a foundation for screening indicators for RA, but also provided new ways of evaluating the quality of Chinese medicinal materials in which saccharides are the main bioactive substances. PMID- 26378511 TI - Spectroscopic Study on the Interaction between Naphthalimide-Polyamine Conjugates and Bovine Serum Albumin (BSA). AB - The effect of a naphthalimide pharmacophore coupled with diverse substituents on the interaction between naphthalimide-polyamine conjugates 1-4 and bovine serum albumin (BSA) was studied by UV absorption, fluorescence and circular dichroism (CD) spectroscopy under physiological conditions (pH = 7.4). The observed spectral quenching of BSA by the compounds indicated that they could bind to BSA. Furthermore, caloric fluorescent tests revealed that the quenching mechanisms of compounds 1-3 were basically static type, but that of compound 4 was closer to a classical type. The Ksv values at room temperature for compound-BSA complexes-1 BSA, 2-BSA, 3-BSA and 4-BSA were 1.438 * 104, 3.190 * 104, 5.700 * 104 and 4.745 * 105, respectively, compared with the value of MINS, 2.863 * 104 at Ex = 280 nm. The obtained quenching constant, binding constant and thermodynamic parameter suggested that the binding between compounds 1-4 with BSA protein, significantly affected by the substituted groups on the naphthalene backbone, was formed by hydrogen bonds, and other principle forces mainly consisting of charged and hydrophobic interactions. Based on results from the analysis of synchronous three dimensional fluorescence and CD spectra, we can conclude that the interaction between compounds 1-4 and BSA protein has little impact on the BSA conformation. Calculated results obtained from in silico molecular simulation showed that compound 1 did not prefer either enzymatic drug sites I or II over the other. However, DSII in BSA was more beneficial than DSI for the binding between compounds 2-4 and BSA protein. The binding between compounds 1-3 and BSA was hydrophobic in nature, compared with the electrostatic interaction between compound 4 and BSA. PMID- 26378512 TI - Beneficial Effects of Ethanolic and Hexanic Rice Bran Extract on Mitochondrial Function in PC12 Cells and the Search for Bioactive Components. AB - Mitochondria are involved in the aging processes that ultimately lead to neurodegeneration and the development of Alzheimer's disease (AD). A healthy lifestyle, including a diet rich in antioxidants and polyphenols, represents one strategy to protect the brain and to prevent neurodegeneration. We recently reported that a stabilized hexanic rice bran extract (RBE) rich in vitamin E and polyphenols (but unsuitable for human consumption) has beneficial effects on mitochondrial function in vitro and in vivo (doi:10.1016/j.phrs.2013.06.008, 10.3233/JAD-132084). To enable the use of RBE as food additive, a stabilized ethanolic extract has been produced. Here, we compare the vitamin E profiles of both extracts and their effects on mitochondrial function (ATP concentrations, mitochondrial membrane potential, mitochondrial respiration and mitochondrial biogenesis) in PC12 cells. We found that vitamin E contents and the effects of both RBE on mitochondrial function were similar. Furthermore, we aimed to identify components responsible for the mitochondria-protective effects of RBE, but could not achieve a conclusive result. alpha-Tocotrienol and possibly also gamma-tocotrienol, alpha-tocopherol and delta-tocopherol might be involved, but hitherto unknown components of RBE or a synergistic effect of various components might also play a role in mediating RBE's beneficial effects on mitochondrial function. PMID- 26378513 TI - Nanoparticles Biosynthesized by Fungi and Yeast: A Review of Their Preparation, Properties, and Medical Applications. AB - In the field of nanotechnology, the use of various biological units instead of toxic chemicals for the reduction and stabilization of nanoparticles, has received extensive attention. Among the many possible bio resources, biologically active products from fungi and yeast represent excellent scaffolds for this purpose. Since fungi and yeast are very effective secretors of extracellular enzymes and number of species grow fast and therefore culturing and keeping them in the laboratory are very simple. They are able to produce metal nanoparticles and nanostructure via reducing enzyme intracellularly or extracellularly. The focus of this review is the application of fungi and yeast in the green synthesis of inorganic nanoparticles. Meanwhile the domain of biosynthesized nanoparticles is somewhat novel; the innovative uses in nano medicine in different areas including the delivery of drug, cancer therapy, antibacterial, biosensors, and MRI and medical imaging are reviewed. The proposed signaling pathways of nanoparticles induced apoptosis in cancerous cells and anti-angiogenesis effects also are reviewed. In this article, we provide a short summary of the present study universally on the utilization of eukaryotes like yeast and fungi in the biosynthesis of nanoparticles (NPs) and their uses. PMID- 26378514 TI - Benzofuranyl Esters: Synthesis, Crystal Structure Determination, Antimicrobial and Antioxidant Activities. AB - A series of five new 2-(1-benzofuran-2-yl)-2-oxoethyl 4-(un/substituted)benzoates 4(a-e), with the general formula of C8H5O(C=O)CH2O(C=O)C6H4X, X = H, Cl, CH3, OCH3 or NO2, was synthesized in high purity and good yield under mild conditions. The synthesized products 4(a-e) were characterized by FTIR, 1H-, (13)C- and 1H (13)C HMQC NMR spectroscopic analysis and their 3D structures were confirmed by single-crystal X-ray diffraction studies. These compounds were screened for their antimicrobial and antioxidant activities. The tested compounds showed antimicrobial ability in the order of 4b < 4a < 4c < 4d < 4e and the highest potency with minimum inhibition concentration (MIC) value of 125 ug/mL was observed for 4e. The results of antioxidant activities revealed the highest activity for compound 4e (32.62% +/- 1.34%) in diphenyl-2-picrylhydrazyl (DPPH) radical scavenging, 4d (31.01% +/- 4.35%) in ferric reducing antioxidant power (FRAP) assay and 4a (27.11% +/- 1.06%) in metal chelating (MC) activity. PMID- 26378515 TI - Cold-Setting Inkjet Printed Titania Patterns Reinforced by Organosilicate Binder. AB - A hybrid organo-silica sol was used as a binder for reinforcing of commercial titanium dioxide nanoparticles (Evonic P25) deposited on glass substrates. The organo-silica binder was prepared by the sol-gel process and mixtures of titania nanoparticles with the binder in various ratios were deposited by materials printing technique. Patterns with both positive and negative features down to 100 um size and variable thickness were reliably printed by Fujifilm Dimatix inkjet printer. All prepared films well adhered onto substrates, however further post printing treatment proved to be necessary in order to improve their reactivity. The influence of UV radiation as well as of thermal sintering on the final electrochemical and photocatalytic properties was investigated. A mixture containing 63 wt % of titania delivered a balanced compromise of mechanical stability, generated photocurrent density and photocatalytic activity. Although the heat treated samples yielded generally higher photocurrent, higher photocatalytic activity towards model aqueous pollutant was observed in the case of UV cured samples because of their superhydrophilic properties. While heat sintering remains the superior processing method for inorganic substrates, UV curing provides a sound treatment option for heat sensitive ones. PMID- 26378516 TI - Design, Synthesis and Biological Evaluation of Novel Substituted N,N'-Diaryl ureas as Potent p38 Inhibitors. AB - A novel series of substituted N,N'-diaryl ureas that act as p38alpha inhibitors have been designed and synthesized based on two key residues (Gly110 and Thr106) that are different in p38alpha MAPK than in other kinases. Preliminary biological evaluation indicated that most compounds possessed good p38alpha inhibitory potencies. Among these compounds, 9g appeared to be the most powerful and is the main compound that we will study in the future. PMID- 26378517 TI - Adaptive Immune Responses in a Multiple Sclerosis Patient with Acute Varicella Zoster Virus Reactivation during Treatment with Fingolimod. AB - Fingolimod, an oral sphingosine 1-phosphate (S1P) receptor modulator, is approved for the treatment of relapsing forms of multiple sclerosis (MS). The interference with S1P signaling leads to retention particularly of chemokine receptor-7 (CCR7) expressing T cells in lymph nodes. The immunological basis of varicella zoster virus (VZV) infections during fingolimod treatment is unclear. Here, we studied the dynamics of systemic and intrathecal immune responses associated with symptomatic VZV reactivation including cessation of fingolimod and initiation of antiviral therapy. Key features in peripheral blood were an about two-fold increase of VZV-specific IgG at diagnosis of VZV reactivation as compared to the previous months, a relative enrichment of effector CD4+ T cells (36% versus mean 12% in controls), and an accelerated reconstitution of absolute lymphocytes counts including a normalized CD4+/CD8+ ratio and reappearance of CCR7+ T cells. In cerebrospinal fluid (CSF) the lymphocytic pleocytosis and CD4+/CD8+ ratios at diagnosis of reactivation and after nine days of fingolimod discontinuation remained unchanged. During this time CCR7+ T cells were not observed in CSF. Further research into fingolimod-associated VZV reactivation and immune reconstitution is mandatory to prevent morbidity and mortality associated with this potentially life-threatening condition. PMID- 26378518 TI - A Novel Function of TET2 in CNS: Sustaining Neuronal Survival. AB - DNA dioxygenases Ten-Eleven Translocation (TET) proteins can catalyze the conversion of 5-methylcytosine (5mC) of DNA to 5-hydroxymethylcytosine (5hmC), and thereby alter the epigenetic state of DNA. The TET family includes TET1, TET2 and TET3 members in mammals. Recently, accumulative research uncovered that TET1 3 occur abundantly in the central nervous system (CNS), and their biological functions have just begun to be investigated. In the present study, we demonstrated that mRNA and protein of TET2 were highly expressed in the cerebral cortex and hippocampus along the whole brain-development process. Further studies showed that TET2 was expressed in various types of cells, especially in most neurons. Subcellular distribution pattern implicated that TET2 is localized in both nucleus and cytoplasm of neurons. Down-regulation of TET2 in cultured cortical neurons with RNA interference implied that TET2 was required for cell survival. In all, our results indicate that neuronal TET2 is positively involved in the regulation of cell survival. PMID- 26378519 TI - Simultaneous Disulfide and Boronic Acid Ester Exchange in Dynamic Combinatorial Libraries. AB - Dynamic combinatorial chemistry has emerged as a promising tool for the discovery of complex receptors in supramolecular chemistry. At the heart of dynamic combinatorial chemistry are the reversible reactions that enable the exchange of building blocks between library members in dynamic combinatorial libraries (DCLs) ensuring thermodynamic control over the system. If more than one reversible reaction operates in a single dynamic combinatorial library, the complexity of the system increases dramatically, and so does its possible applications. One can imagine two reversible reactions that operate simultaneously or two reversible reactions that operate independently. Both these scenarios have advantages and disadvantages. In this contribution, we show how disulfide exchange and boronic ester transesterification can function simultaneous in dynamic combinatorial libraries under appropriate conditions. We describe the detailed studies necessary to establish suitable reaction conditions and highlight the analytical techniques appropriate to study this type of system. PMID- 26378520 TI - Identification of Genes Putatively Involved in Chitin Metabolism and Insecticide Detoxification in the Rice Leaf Folder (Cnaphalocrocis medinalis) Larvae through Transcriptomic Analysis. AB - The rice leaf roller (Cnaphalocrocis medinalis) is one of the most destructive agricultural pests. Due to its migratory behavior, it is difficult to control worldwide. To date, little is known about major genes of C. medinalis involved in chitin metabolism and insecticide detoxification. In order to obtain a comprehensive genome dataset of C. medinalis, we conducted de novo transcriptome sequencing which focused on the major feeding stage of fourth-instar larvae, and our work revealed useful information on chitin metabolism and insecticide detoxification and target genes of C. medinalis. We acquired 29,367,797 Illumina reads and assembled these reads into 63,174 unigenes with an average length of 753 bp. Among these unigenes, 31,810 were annotated against the National Center for Biotechnology Information non-redundant (NCBI nr) protein database, resulting in 24,246, 8669 and 18,176 assigned to Swiss-Prot, clusters of orthologous group (COG), and gene ontology (GO), respectively. We were able to map 10,043 unigenes into 285 pathways using the Kyoto Encyclopedia of Genes and Genomes Pathway database (KEGG). Specifically, 16 genes, including five chitin deacetylases, two chitin synthases, five chitinases and four other related enzymes, were identified to be putatively involved in chitin biosynthesis and degradation, whereas 360 genes, including cytochrome P450s, glutathione S-transferases, esterases, and acetylcholinesterases, were found to be potentially involved in insecticide detoxification or as insecticide targets. The reliability of the transcriptome data was determined by reverse transcription quantitative PCR (RT-qPCR) for the selected genes. Our data serves as a new and valuable sequence resource for genomic studies on C. medinalis. The findings should improve our understanding of C. medinalis genetics and contribute to management of this important agricultural pest. PMID- 26378521 TI - GCN5 Potentiates Glioma Proliferation and Invasion via STAT3 and AKT Signaling Pathways. AB - The general control of nucleotide synthesis 5 (GCN5), which is one kind of lysine acetyltransferases, regulates a number of cellular processes, such as cell proliferation, differentiation, cell cycle and DNA damage repair. However, its biological role in human glioma development remains elusive. In the present study, we firstly reported that GCN5 was frequently overexpressed in human glioma tissues and GCN5 was positively correlated with proliferation of cell nuclear antigen PCNA and matrix metallopeptidase MMP9. Meanwhile, down-regulation of GCN5 by siRNA interfering inhibited glioma cell proliferation and invasion. In addition, GCN5 knockdown reduced expression of p-STAT3, p-AKT, PCNA and MMP9 and increased the expression of p21 in glioma cells. In conclusion, GCN5 exhibited critical roles in glioma development by regulating cell proliferation and invasion, which suggested that GCN5 might be a potential molecular target for glioma treatment. PMID- 26378522 TI - Ghrelin Attenuates Liver Fibrosis through Regulation of TGF-beta1 Expression and Autophagy. AB - Ghrelin is a stomach-derived growth hormone secretagogue that promotes various physiological effects, including energy metabolism and amelioration of inflammation. The purpose of this study was to investigate the protective mechanism of ghrelin against liver fibrosis. Liver fibrosis was induced in C57BL/6 mice by intraperitoneal injection of CCl4 (2.0 mL/kg of 10% CCl4 v/v solution in peanut oil) two times per week for eight weeks. Ghrelin (10 MUg/kg) was intraperitoneally injected two times per week for eight weeks. A second murine liver fibrosis model was induced by bile duct ligation (BDL) and concurrent ghrelin administration for four weeks. Hematoxylin eosin (H&E), and Masson's trichrome were used to detect pathological changes to liver tissue. Western blotting was used to detect protein levels of transforming growth factor (TGF)-beta1, phosphorylated Smad3 (p-Smad3), I-collage, alpha-smooth muscle actin (alpha-SMA), matrix metalloproteinases (MMPs) 2, tissue inhibitor of matrix metalloproteinases (TIMPs) 1, phosphorylated NF-kappaB (p-NF-kappaB), and microtubule-associated protein light chain 3 (LC3). In addition, qRT-PCR was used to detect mRNA levels of TGF-beta1, I-collage, alpha-SMA, MMP2, TIMP1 and LC3, while levels of TGF-beta1, p-Smad3, I-collage, alpha-SMA, and LC3 were detected immunohistochemically. Levels of aspartate aminotransferase and alanine aminotransferase were significantly decreased by ghrelin treatment. Ghrelin administration also significantly reduced the extent of pathological changes in both murine liver fibrosis models. Expression levels of I-collage and alpha-SMA in both models were clearly reduced by ghrelin administration. Furthermore, ghrelin treatment decreased protein expression of TGF-beta1 and p-Smad3. The protein levels of NF-kappaB and LC3 were increased in the CCl4- and BDL-treatment groups but were significantly reduced following ghrelin treatment. In addition, ghrelin inhibited extracellular matrix formation by decreasing NF-kappaB expression and maintaining the balance between MMP2 and TIMP1. Our results demonstrated that ghrelin attenuates liver fibrosis via inhibition of the TGF beta1/Smad3 and NF-kappaB signaling pathways, as well as autophagy suppression. PMID- 26378523 TI - Effects of Oral Administration of Chitin Nanofiber on Plasma Metabolites and Gut Microorganisms. AB - The aim of this study was to examine the effects of oral administration of chitin nanofibers (CNFs) and surface-deacetylated (SDA) CNFs on plasma metabolites using metabolome analysis. Furthermore, we determined the changes in gut microbiota and fecal organic acid concentrations following oral administrations of CNFs and SDACNFs. Healthy female mice (six-week-old) were fed a normal diet and administered tap water with 0.1% (v/v) CNFs or SDACNFs for 28 days. Oral administration of CNFs increased plasma levels of adenosine triphosphate (ATP), adenosine diphosphate (ADP), and serotonin (5-hydroxytryptamine, 5-HT). Oral administration of SDACNFs affected the metabolisms of acyl-carnitines and fatty acids. The fecal organic level analysis indicated that oral administration of CNFs stimulated and activated the functions of microbiota. These results indicate that oral administration of CNFs increases plasma levels of ATP and 5-HT via activation of gut microbiota. PMID- 26378524 TI - New Cytotoxic 24-Homoscalarane Sesterterpenoids from the Sponge Ircinia felix. AB - Two new 24-homoscalarane sesterterpenoids, felixins F (1) and G (2), were isolated from the sponge Ircinia felix. The structures of new homoscalaranes 1 and 2 were elucidated by extensive spectroscopic methods, particularly with one dimensional (1D) and two-dimensional (2D) NMR, and, by comparison, the spectral data with those of known analogues. The cytotoxicity of 1 and 2 against the proliferation of a limited panel of tumor cell lines was evaluated and 1 was found to show cytotoxicity toward the leukemia K562, MOLT-4, and SUP-T1 cells (IC50 <= 5.0 MUM). PMID- 26378525 TI - Metabolite Profiling of Diverse Rice Germplasm and Identification of Conserved Metabolic Markers of Rice Roots in Response to Long-Term Mild Salinity Stress. AB - The sensitivity of rice to salt stress greatly depends on growth stages, organ types and cultivars. Especially, the roots of young rice seedlings are highly salt-sensitive organs that limit plant growth, even under mild soil salinity conditions. In an attempt to identify metabolic markers of rice roots responding to salt stress, metabolite profiling was performed by 1H-NMR spectroscopy in 38 rice genotypes that varied in biomass accumulation under long-term mild salinity condition. Multivariate statistical analysis showed separation of the control and salt-treated rice roots and rice genotypes with differential growth potential. By quantitative analyses of 1H-NMR data, five conserved salt-responsive metabolic markers of rice roots were identified. Sucrose, allantoin and glutamate accumulated by salt stress, whereas the levels of glutamine and alanine decreased. A positive correlation of metabolite changes with growth potential and salt tolerance of rice genotypes was observed for allantoin and glutamine. Adjustment of nitrogen metabolism in rice roots is likely to be closely related to maintain the growth potential and increase the stress tolerance of rice. PMID- 26378526 TI - Molecular Identification of Dendrobium Species (Orchidaceae) Based on the DNA Barcode ITS2 Region and Its Application for Phylogenetic Study. AB - The over-collection and habitat destruction of natural Dendrobium populations for their commercial medicinal value has led to these plants being under severe threat of extinction. In addition, many Dendrobium plants are similarly shaped and easily confused during the absence of flowering stages. In the present study, we examined the application of the ITS2 region in barcoding and phylogenetic analyses of Dendrobium species (Orchidaceae). For barcoding, ITS2 regions of 43 samples in Dendrobium were amplified. In combination with sequences from GenBank, the sequences were aligned using Clustal W and genetic distances were computed using MEGA V5.1. The success rate of PCR amplification and sequencing was 100%. There was a significant divergence between the inter- and intra-specific genetic distances of ITS2 regions, while the presence of a barcoding gap was obvious. Based on the BLAST1, nearest distance and TaxonGAP methods, our results showed that the ITS2 regions could successfully identify the species of most Dendrobium samples examined; Second, we used ITS2 as a DNA marker to infer phylogenetic relationships of 64 Dendrobium species. The results showed that cluster analysis using the ITS2 region mainly supported the relationship between the species of Dendrobium established by traditional morphological methods and many previous molecular analyses. To sum up, the ITS2 region can not only be used as an efficient barcode to identify Dendrobium species, but also has the potential to contribute to the phylogenetic analysis of the genus Dendrobium. PMID- 26378527 TI - Identification of Ramie Genes in Response to Pratylenchus coffeae Infection Challenge by Digital Gene Expression Analysis. AB - Root lesion disease, caused by Pratylenchus coffeae, seriously impairs the growth and yield of ramie, an important natural fiber crop. The ramie defense mechanism against P. coffeae infection is poorly understood, which hinders efforts to improve resistance via breeding programs. In this study, the transcriptome of the resistant ramie cultivar Qingdaye was characterized using Illumina sequence technology. About 46.3 million clean pair end (PE) reads were generated and assembled into 40,826 unigenes with a mean length of 830 bp. Digital gene expression (DGE) analysis was performed on both the control roots (CK) and P. coffeae-challenged roots (CH), and the differentially expressed genes (DEGs) were identified. Approximately 10.16 and 8.07 million cDNA reads in the CK and CH cDNA libraries were sequenced, respectively. A total of 137 genes exhibited different transcript abundances between the two libraries. Among them, the expressions of 117 and 20 DEGs were up- and down-regulated in P. coffeae-challenged ramie, respectively. The expression patterns of 15 candidate genes determined by qRT-PCR confirmed the results of DGE analysis. Time-course expression profiles of eight defense-related genes in susceptible and resistant ramie cultivars were different after P. coffeae inoculation. The differential expression of protease inhibitors, pathogenesis-related proteins (PRs), and transcription factors in resistant and susceptible ramie during P. coffeae infection indicated that cystatin likely plays an important role in nematode resistance. PMID- 26378528 TI - Gene Expression of Type VI Secretion System Associated with Environmental Survival in Acidovorax avenae subsp. avenae by Principle Component Analysis. AB - Valine glycine repeat G (VgrG) proteins are regarded as one of two effectors of Type VI secretion system (T6SS) which is a complex multi-component secretion system. In this study, potential biological roles of T6SS structural and VgrG genes in a rice bacterial pathogen, Acidovorax avenae subsp. avenae (Aaa) RS-1, were evaluated under seven stress conditions using principle component analysis of gene expression. The results showed that growth of the pathogen was reduced by H2O2 and paraquat-induced oxidative stress, high salt, low temperature, and vgrG mutation, compared to the control. However, pathogen growth was unaffected by co culture with a rice rhizobacterium Burkholderia seminalis R456. In addition, expression of 14 T6SS structural and eight vgrG genes was significantly changed under seven conditions. Among different stress conditions, high salt, and low temperature showed a higher effect on the expression of T6SS gene compared with host infection and other environmental conditions. As a first report, this study revealed an association of T6SS gene expression of the pathogen with the host infection, gene mutation, and some common environmental stresses. The results of this research can increase understanding of the biological function of T6SS in this economically-important pathogen of rice. PMID- 26378529 TI - Size Does Matter: Staging of Silene latifolia Floral Buds for Transcriptome Studies. AB - Dioecious plants in the Caryophyllaceae family are susceptible to infection by members of the anthericolous smut fungi. In our studies of the Silene latifolia/Microbotryum lychnidis-dioicae pathosystem, we were interested in characterizing the plant-pathogen interaction at the molecular level before and during teliosporogenesis. This takes place during floral bud development, and we hoped to capture the interaction by Illumina Next-Gen RNA-Sequencing. Using previous literature that documented the stages of the floral buds for S. latifolia, we examined the floral buds from plants grown and infected under growth chamber conditions, using the disserting microscope to determine the stage of floral buds based on the morphology. We compiled the information and determined the size of floral buds that correspond to the desired stages of development for tissue collection, for the purpose of RNA-sequencing. This offers a practical approach for researchers who require a large number of floral buds/tissue categorized by stages of development, ascertaining whether infected/uninfected buds are at comparable stages of development and whether this also holds true for male vs. female buds. We also document our experience in infecting the plants and some of the unusual morphologies we observed after infection. PMID- 26378530 TI - Identification of Conserved and Novel MicroRNAs during Tail Regeneration in the Mexican Axolotl. AB - The Mexican axolotl salamander (Ambystoma mexicanum) is one member of a select group of vertebrate animals that have retained the amazing ability to regenerate multiple body parts. In addition to being an important model system for regeneration, the axolotl has also contributed extensively to studies of basic development. While many genes known to play key roles during development have now been implicated in various forms of regeneration, much of the regulatory apparatus controlling the underlying molecular circuitry remains unknown. In recent years, microRNAs have been identified as key regulators of gene expression during development, in many diseases and also, increasingly, in regeneration. Here, we have used deep sequencing combined with qRT-PCR to undertake a comprehensive identification of microRNAs involved in regulating regeneration in the axolotl. Specifically, among the microRNAs that we have found to be expressed in axolotl tissues, we have identified 4564 microRNA families known to be widely conserved among vertebrates, as well as 59,811 reads of putative novel microRNAs. These findings support the hypothesis that microRNAs play key roles in managing the precise spatial and temporal patterns of gene expression that ensures the correct regeneration of missing tissues. PMID- 26378532 TI - Push-Broom-Type Very High-Resolution Satellite Sensor Data Correction Using Combined Wavelet-Fourier and Multiscale Non-Local Means Filtering. AB - In very high-resolution (VHR) push-broom-type satellite sensor data, both destriping and denoising methods have become chronic problems and attracted major research advances in the remote sensing fields. Since the estimation of the original image from a noisy input is an ill-posed problem, a simple noise removal algorithm cannot preserve the radiometric integrity of satellite data. To solve these problems, we present a novel method to correct VHR data acquired by a push broom-type sensor by combining wavelet-Fourier and multiscale non-local means (NLM) filters. After the wavelet-Fourier filter separates the stripe noise from the mixed noise in the wavelet low- and selected high-frequency sub-bands, random noise is removed using the multiscale NLM filter in both low- and high-frequency sub-bands without loss of image detail. The performance of the proposed method is compared to various existing methods on a set of push-broom-type sensor data acquired by Korean Multi-Purpose Satellite 3 (KOMPSAT-3) with severe stripe and random noise, and the results of the proposed method show significantly improved enhancement results over existing state-of-the-art methods in terms of both qualitative and quantitative assessments. PMID- 26378531 TI - Inhibition of Hepatocyte Apoptosis: An Important Mechanism of Corn Peptides Attenuating Liver Injury Induced by Ethanol. AB - In this study, the effects of mixed corn peptides and synthetic pentapeptide (QLLPF) on hepatocyte apoptosis induced by ethanol were investigated in vivo. QLLPF, was previously characterized from corn protein hydrolysis, which had been shown to exert good facilitating alcohol metabolism activity. Mice were pre treated with the mixed corn peptides and the pentapeptide for 1 week and then treated with ethanol. After treatment of three weeks, the biochemical indices and the key ethanol metabolizing enzymes, the serum TNF-alpha, liver TGF-beta1 concentrations and the protein expressions related to apoptosis were determined. We found that the Bcl-2, Bax and cytochrome c expressions in the intrinsic pathway and the Fas, FasL and NF-kappaB expressions in the extrinsic pathway together with higher TNF-alpha and TGF-beta1 concentrations were reversed compared with the model group by both the mixed corn peptides and the pentapeptide. The activation of caspase3 was also suppressed. Additionally, apoptosis was further confirmed with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and the TUNEL assay demonstrated peptides suppressed hepatocyte apoptosis. Our results suggest that apoptosis induced by ethanol is alleviated in response to the treatment of corn peptides, potentially due to reversing the related protein expression. PMID- 26378533 TI - Vision-Aided RAIM: A New Method for GPS Integrity Monitoring in Approach and Landing Phase. AB - In the 1980s, Global Positioning System (GPS) receiver autonomous integrity monitoring (RAIM) was proposed to provide the integrity of a navigation system by checking the consistency of GPS measurements. However, during the approach and landing phase of a flight path, where there is often low GPS visibility conditions, the performance of the existing RAIM method may not meet the stringent aviation requirements for availability and integrity due to insufficient observations. To solve this problem, a new RAIM method, named vision aided RAIM (VA-RAIM), is proposed for GPS integrity monitoring in the approach and landing phase. By introducing landmarks as pseudo-satellites, the VA-RAIM enriches the navigation observations to improve the performance of RAIM. In the method, a computer vision system photographs and matches these landmarks to obtain additional measurements for navigation. Nevertheless, the challenging issue is that such additional measurements may suffer from vision errors. To ensure the reliability of the vision measurements, a GPS-based calibration algorithm is presented to reduce the time-invariant part of the vision errors. Then, the calibrated vision measurements are integrated with the GPS observations for integrity monitoring. Simulation results show that the VA-RAIM outperforms the conventional RAIM with a higher level of availability and fault detection rate. PMID- 26378534 TI - Urban Automation Networks: Current and Emerging Solutions for Sensed Data Collection and Actuation in Smart Cities. AB - Urban Automation Networks (UANs) are being deployed worldwide in order to enable Smart City applications. Given the crucial role of UANs, as well as their diversity, it is critically important to assess their properties and trade-offs. This article introduces the requirements and challenges for UANs, characterizes the main current and emerging UAN paradigms, provides guidelines for their design and/or choice, and comparatively examines their performance in terms of a variety of parameters including coverage, power consumption, latency, standardization status and economic cost. PMID- 26378535 TI - A Mathematical Model of the Thermo-Anemometric Flowmeter. AB - A thermo-anemometric flowmeter design and the principles of its work are presented in the article. A mathematical model of the temperature field in a stream of biofuel is proposed. This model allows one to determine the fuel consumption with high accuracy. Numerical modeling of the heater heat balance in the fuel flow of a thermo-anemometric flowmeter is conducted and the results are analyzed. Methods for increasing the measurement speed and accuracy of a thermo anemometric flowmeter are proposed. PMID- 26378536 TI - Piezotronic Effect: An Emerging Mechanism for Sensing Applications. AB - Strain-induced polarization charges in a piezoelectric semiconductor effectively modulate the band structure near the interface and charge carrier transport. Fundamental investigation of the piezotronic effect has attracted broad interest, and various sensing applications have been demonstrated. This brief review discusses the fundamentals of the piezotronic effect, followed by a review highlighting important applications for strain sensors, pressure sensors, chemical sensors, photodetectors, humidity sensors and temperature sensors. Finally, the review offers some perspectives and outlook for this new field of multi-functional sensing enabled by the piezotronic effect. PMID- 26378537 TI - An Electrochemical Impedance Spectroscopy-Based Technique to Identify and Quantify Fermentable Sugars in Pineapple Waste Valorization for Bioethanol Production. AB - Electrochemical Impedance Spectroscopy (EIS) has been used to develop a methodology able to identify and quantify fermentable sugars present in the enzymatic hydrolysis phase of second-generation bioethanol production from pineapple waste. Thus, a low-cost non-destructive system consisting of a stainless double needle electrode associated to an electronic equipment that allows the implementation of EIS was developed. In order to validate the system, different concentrations of glucose, fructose and sucrose were added to the pineapple waste and analyzed both individually and in combination. Next, statistical data treatment enabled the design of specific Artificial Neural Networks-based mathematical models for each one of the studied sugars and their respective combinations. The obtained prediction models are robust and reliable and they are considered statistically valid (CCR% > 93.443%). These results allow us to introduce this EIS-based technique as an easy, fast, non-destructive, and in-situ alternative to the traditional laboratory methods for enzymatic hydrolysis monitoring. PMID- 26378538 TI - Evaluating Sentinel-2 for Lakeshore Habitat Mapping Based on Airborne Hyperspectral Data. AB - Monitoring of lakeshore ecosystems requires fine-scale information to account for the high biodiversity typically encountered in the land-water ecotone. Sentinel-2 is a satellite with high spatial and spectral resolution and improved revisiting frequency and is expected to have significant potential for habitat mapping and classification of complex lakeshore ecosystems. In this context, investigations of the capabilities of Sentinel-2 in regard to the spatial and spectral dimensions are needed to assess its potential and the quality of the expected output. This study presents the first simulation of the high spatial resolution (i.e., 10 m and 20 m) bands of Sentinel-2 for lakeshore mapping, based on the satellite's Spectral Response Function and hyperspectral airborne data collected over Lake Balaton, Hungary in August 2010. A comparison of supervised classifications of the simulated products is presented and the information loss from spectral aggregation and spatial upscaling in the context of lakeshore vegetation classification is discussed. We conclude that Sentinel-2 imagery has a strong potential for monitoring fine-scale habitats, such as reed beds. PMID- 26378539 TI - Map as a Service: A Framework for Visualising and Maximising Information Return from Multi-ModalWireless Sensor Networks. AB - This paper presents a distributed information extraction and visualisation service, called the mapping service, for maximising information return from large scale wireless sensor networks. Such a service would greatly simplify the production of higher-level, information-rich, representations suitable for informing other network services and the delivery of field information visualisations. The mapping service utilises a blend of inductive and deductive models to map sense data accurately using externally available knowledge. It utilises the special characteristics of the application domain to render visualisations in a map format that are a precise reflection of the concrete reality. This service is suitable for visualising an arbitrary number of sense modalities. It is capable of visualising from multiple independent types of the sense data to overcome the limitations of generating visualisations from a single type of sense modality. Furthermore, the mapping service responds dynamically to changes in the environmental conditions, which may affect the visualisation performance by continuously updating the application domain model in a distributed manner. Finally, a distributed self-adaptation function is proposed with the goal of saving more power and generating more accurate data visualisation. We conduct comprehensive experimentation to evaluate the performance of our mapping service and show that it achieves low communication overhead, produces maps of high fidelity, and further minimises the mapping predictive error dynamically through integrating the application domain model in the mapping service. PMID- 26378540 TI - New Fast Fall Detection Method Based on Spatio-Temporal Context Tracking of Head by Using Depth Images. AB - In order to deal with the problem of projection occurring in fall detection with two-dimensional (2D) grey or color images, this paper proposed a robust fall detection method based on spatio-temporal context tracking over three-dimensional (3D) depth images that are captured by the Kinect sensor. In the pre-processing procedure, the parameters of the Single-Gauss-Model (SGM) are estimated and the coefficients of the floor plane equation are extracted from the background images. Once human subject appears in the scene, the silhouette is extracted by SGM and the foreground coefficient of ellipses is used to determine the head position. The dense spatio-temporal context (STC) algorithm is then applied to track the head position and the distance from the head to floor plane is calculated in every following frame of the depth image. When the distance is lower than an adaptive threshold, the centroid height of the human will be used as the second judgment criteria to decide whether a fall incident happened. Lastly, four groups of experiments with different falling directions are performed. Experimental results show that the proposed method can detect fall incidents that occurred in different orientations, and they only need a low computation complexity. PMID- 26378541 TI - Optimization and Control of Cyber-Physical Vehicle Systems. AB - A cyber-physical system (CPS) is composed of tightly-integrated computation, communication and physical elements. Medical devices, buildings, mobile devices, robots, transportation and energy systems can benefit from CPS co-design and optimization techniques. Cyber-physical vehicle systems (CPVSs) are rapidly advancing due to progress in real-time computing, control and artificial intelligence. Multidisciplinary or multi-objective design optimization maximizes CPS efficiency, capability and safety, while online regulation enables the vehicle to be responsive to disturbances, modeling errors and uncertainties. CPVS optimization occurs at design-time and at run-time. This paper surveys the run time cooperative optimization or co-optimization of cyber and physical systems, which have historically been considered separately. A run-time CPVS is also cooperatively regulated or co-regulated when cyber and physical resources are utilized in a manner that is responsive to both cyber and physical system requirements. This paper surveys research that considers both cyber and physical resources in co-optimization and co-regulation schemes with applications to mobile robotic and vehicle systems. Time-varying sampling patterns, sensor scheduling, anytime control, feedback scheduling, task and motion planning and resource sharing are examined. PMID- 26378542 TI - Deep Coupled Integration of CSAC and GNSS for Robust PNT. AB - Global navigation satellite systems (GNSS) are the most widely used positioning, navigation, and timing (PNT) technology. However, a GNSS cannot provide effective PNT services in physical blocks, such as in a natural canyon, canyon city, underground, underwater, and indoors. With the development of micro electromechanical system (MEMS) technology, the chip scale atomic clock (CSAC) gradually matures, and performance is constantly improved. A deep coupled integration of CSAC and GNSS is explored in this thesis to enhance PNT robustness. "Clock coasting" of CSAC provides time synchronized with GNSS and optimizes navigation equations. However, errors of clock coasting increase over time and can be corrected by GNSS time, which is stable but noisy. In this paper, weighted linear optimal estimation algorithm is used for CSAC-aided GNSS, while Kalman filter is used for GNSS-corrected CSAC. Simulations of the model are conducted, and field tests are carried out. Dilution of precision can be improved by integration. Integration is more accurate than traditional GNSS. When only three satellites are visible, the integration still works, whereas the traditional method fails. The deep coupled integration of CSAC and GNSS can improve the accuracy, reliability, and availability of PNT. PMID- 26378543 TI - Aircraft Detection in High-Resolution SAR Images Based on a Gradient Textural Saliency Map. AB - This paper proposes a new automatic and adaptive aircraft target detection algorithm in high-resolution synthetic aperture radar (SAR) images of airport. The proposed method is based on gradient textural saliency map under the contextual cues of apron area. Firstly, the candidate regions with the possible existence of airport are detected from the apron area. Secondly, directional local gradient distribution detector is used to obtain a gradient textural saliency map in the favor of the candidate regions. In addition, the final targets will be detected by segmenting the saliency map using CFAR-type algorithm. The real high-resolution airborne SAR image data is used to verify the proposed algorithm. The results demonstrate that this algorithm can detect aircraft targets quickly and accurately, and decrease the false alarm rate. PMID- 26378544 TI - Pre-Processing Effect on the Accuracy of Event-Based Activity Segmentation and Classification through Inertial Sensors. AB - Inertial sensors are increasingly being used to recognize and classify physical activities in a variety of applications. For monitoring and fitness applications, it is crucial to develop methods able to segment each activity cycle, e.g., a gait cycle, so that the successive classification step may be more accurate. To increase detection accuracy, pre-processing is often used, with a concurrent increase in computational cost. In this paper, the effect of pre-processing operations on the detection and classification of locomotion activities was investigated, to check whether the presence of pre-processing significantly contributes to an increase in accuracy. The pre-processing stages evaluated in this study were inclination correction and de-noising. Level walking, step ascending, descending and running were monitored by using a shank-mounted inertial sensor. Raw and filtered segments, obtained from a modified version of a rule-based gait detection algorithm optimized for sequential processing, were processed to extract time and frequency-based features for physical activity classification through a support vector machine classifier. The proposed method accurately detected >99% gait cycles from raw data and produced >98% accuracy on these segmented gait cycles. Pre-processing did not substantially increase classification accuracy, thus highlighting the possibility of reducing the amount of pre-processing for real-time applications. PMID- 26378545 TI - Improving the Detection Limit in a Capillary Raman System for In Situ Gas Analysis by Means of Fluorescence Reduction. AB - Raman spectroscopy for low-pressure or trace gas analysis is rather challenging, in particular in process control applications requiring trace detection and real time response; in general, enhancement techniques are required. One possible enhancement approach which enjoys increasing popularity makes use of an internally-reflective capillary as the gas cell. However, in the majority of cases, such capillary systems were often limited in their achievable sensitivity by a significant fluorescence background, which is generated as a consequence of interactions between the laser light and optical glass components in the setup. In order to understand and counteract these problems we have investigated a range of fluorescence-reducing measures, including the rearrangement of optical elements, and the replacement of glass components--including the capillary itself -by metal alternatives. These studies now have led to a capillary setup in which fluorescence is practically eliminated and substantial signal enhancement over standard Raman setups is achieved. With this improved (prototype) setup, detection limits of well below 1 mbar could be obtained in sub-second acquisition times, demonstrating the potential of capillary Raman spectroscopy for real-time, in situ gas sensing and process control applications, down to trace level concentrations. PMID- 26378546 TI - Temperature and Humidity Sensor Powered by an Individual Microbial Fuel Cell in a Power Management System. AB - Microbial fuel cells (MFCs) are of increasing interest as bioelectrochemical systems for decomposing organic materials and converting chemical energy into electricity. The main challenge for this technology is that the low power and voltage of the devices restricts the use of MFCs in practical applications. In this paper, a power management system (PMS) is developed to store the energy and export an increased voltage. The designed PMS successfully increases the low voltage generated by an individual MFC to a high potential of 5 V, capable of driving a wireless temperature and humidity sensor based on nRF24L01 data transmission modules. With the PMS, MFCs can intermittently power the sensor for data transmission to a remote receiver. It is concluded that even an individual MFC can supply the energy required to power the sensor and telemetry system with the designed PMS. The presented PMS can be widely used for unmanned environmental monitoring such as wild rivers, lakes, and adjacent water areas, and offers promise for further advances in MFC technology. PMID- 26378547 TI - Development and Application of a Novel SPE-Method for Bioassay-Guided Fractionation of Marine Extracts. AB - The biological diversity of marine habitats is a unique source of chemical compounds with potential use as pharmaceuticals, cosmetics and dietary supplements. However, biological screening and chemical analysis of marine extracts pose specific technical constraints and require adequate sample preparation. Here we report an improved method on Solid Phase Extraction (SPE) to fractionate organic extracts containing high concentration of salt that hampers the recovery of secondary metabolites. The procedure uses a water suspension to load the extracts on a poly(styrene-divynylbenzene)-based support and a stepwise organic solvent elution to effectively desalt and fractionate the organic components. The novel protocol has been tested on MeOH-soluble material from three model organisms (Reniera sarai, Dendrilla membranosa and Amphidinium carterae) and was validated on a small panel of 47 marine samples, including sponges and protists, within discovery programs for identification of immuno stimulatory and anti-infective natural products. PMID- 26378548 TI - Astaxanthin as a Potential Neuroprotective Agent for Neurological Diseases. AB - Neurological diseases, which consist of acute injuries and chronic neurodegeneration, are the leading causes of human death and disability. However, the pathophysiology of these diseases have not been fully elucidated, and effective treatments are still lacking. Astaxanthin, a member of the xanthophyll group, is a red-orange carotenoid with unique cell membrane actions and diverse biological activities. More importantly, there is evidence demonstrating that astaxanthin confers neuroprotective effects in experimental models of acute injuries, chronic neurodegenerative disorders, and neurological diseases. The beneficial effects of astaxanthin are linked to its oxidative, anti-inflammatory, and anti-apoptotic characteristics. In this review, we will focus on the neuroprotective properties of astaxanthin and explore the underlying mechanisms in the setting of neurological diseases. PMID- 26378549 TI - Determination of Lipid Hydroperoxides in Marine Diatoms by the FOX2 Assay. AB - Ecologically-relevant marine diatoms produce a plethora of bioactive oxylipins deriving from fatty acid oxidation, including aldehydes, hydroxy-fatty acids, epoxy-hydroxy-fatty acids, and oxo-acids. These secondary metabolites have been related to the negative effect of diatoms on copepod reproduction, causing low hatching success and teratogenesis in the offspring during periods of intense diatom blooms. The common intermediates in the formation of oxylipins are fatty acid hydroperoxides. The quantitative measurement of these intermediates can fundamentally contribute to understanding the function and role of lipoxygenase metabolites in diatom-copepod interactions. Here, we describe the successful adaptation of the ferrous oxidation-xylenol orange 2 (FOX2) assay to diatom samples, which showed several advantages over other spectrophotometric and polarographic methods tested in the present work. Using this method we assessed fatty acid hydroperoxide levels in three diatom species: Skeletonema marinoi, Thalassiosira rotula, and Chaetoceros affinis, and discuss results in light of the literature data on their detrimental effects on copepod reproduction. PMID- 26378551 TI - The Influence of Climate Change on Atmospheric Deposition of Mercury in the Arctic-A Model Sensitivity Study. AB - Mercury (Hg) is a global pollutant with adverse health effects on humans and wildlife. It is of special concern in the Arctic due to accumulation in the food web and exposure of the Arctic population through a rich marine diet. Climate change may alter the exposure of the Arctic population to Hg. We have investigated the effect of climate change on the atmospheric Hg transport to and deposition within the Arctic by making a sensitivity study of how the atmospheric chemistry-transport model Danish Eulerian Hemispheric Model (DEHM) reacts to climate change forcing. The total deposition of Hg to the Arctic is 18% lower in the 2090s compared to the 1990s under the applied Special Report on Emissions Scenarios (SRES-A1B) climate scenario. Asia is the major anthropogenic source area (25% of the deposition to the Arctic) followed by Europe (6%) and North America (5%), with the rest arising from the background concentration, and this is independent of the climate. DEHM predicts between a 6% increase (Status Quo scenario) and a 37% decrease (zero anthropogenic emissions scenario) in Hg deposition to the Arctic depending on the applied emission scenario, while the combined effect of future climate and emission changes results in up to 47% lower Hg deposition. PMID- 26378550 TI - Overexpression of G6PD and HSP90 Beta in Mice with Benzene Exposure Revealed by Serum Peptidome Analysis. AB - The small peptides representation of the original proteins are a valuable source of information that can be used as biomarkers involved in toxicity mechanism for chemical exposure. The aim of this study is to investigate serum peptide biomarkers of benzene exposure. C57BL/6 mice were enrolled into control group and benzene groups of 150 and 300 mg/kg/d Serum peptides were identified by mass spectrometry using an assisted laser desorption ionization/time of flight mass spectrometry (MS). Differential peptide spectra were obtained by tandem mass spectrometry and analyzed by searching the International Protein Index using the Sequest program. Forty-one peptide peaks were found in the range of 1000-10,000 Da molecular weight. Among them, seven peaks showed significantly different expression between exposure groups and control group. Two peptide peaks (1231.2 and 1241.8), which showed a two-fold increase in expression, were sequenced and confirmed as glucose 6-phosphate dehydrogenase (G6PD) and heat shock protein 90 Beta (HSP90 Beta), respectively. Furthermore, the expression of the two proteins in liver cells showed the same trend as in serum. In conclusion, G6PD and HSP90 beta might be the candidate serum biomarkers of benzene exposure. It also provided possible clues for the molecular mechanism of benzene-induced oxidative stress. PMID- 26378552 TI - Powder Activated Carbon Pretreatment of a Microfiltration Membrane for the Treatment of Surface Water. AB - This study focused on the effect of powder activated carbon (PAC) adsorption on microfiltration (MF) membrane performance. The results showed that PAC pretreatment offered high organic matter removal rates for both dissolved organic carbon (DOC) and ultraviolet absorbance at 254 nm (UV254) during 10-200 mg/L PAC dosage. The removal efficiencies of organic matter by MF membrane filtration decreased with the increase of organic matter removal rate by PAC adsorption. PAC mainly removed organic matter of about 3 kDa molecular weight (MW). MF membrane maintained more than 5 kDa MW organic matter on the membrane after PAC adsorption. The results of membrane filtration indicated that PAC pretreatment slightly promoted membrane flux, regardless of PAC dosage. It seems that the organic matter fouling membrane was concentrated in more than 3 kDa MW. PAC removed markedly less than 3 kDa MW organic matter and had less effect on more than 3 kDa organic matter. Thus, PAC cannot reduce membrane fouling. PMID- 26378553 TI - Remediation of Rare Earth Element Pollutants by Sorption Process Using Organic Natural Sorbents. AB - The effects of the sorption of environmental applications by various source materials of natural organic matter, i.e., bone powder, was examined. Sorption capacities and subsequent rare earth element retention characteristics of all metals tested were markedly increased by ionic task-specific. In this study, the abilities of three models' isotherms widely were used for the equilibrium sorption data: Langmuir, Freundlich and Redlich-Peterson. For all studied metal ions the maximum adsorption capacity is close to those experimentally determined. The characteristic parameters for each isotherm and related coefficients of determination have been determined. The experimental data achieved excellent fits within the following isotherms in the order: Langmuir > Redlich-Peterson > Freundlich, based on their coefficient of determination values. The bone powder has developed higher adsorption performance in the removal process of Nd(III), Eu(III), La(III) from aqueous solutions than in the case of the removal process of Cs(I), Sr(II) and Tl(I) from aqueous solutions. The described relationships provide direct experimental evidence that the sorption-desorption properties of bone powder are closely related to their degree of the type of the metal. The results suggest a potential for obtaining efficient and cost-effective engineered natural organic sorbents for environmental applications. PMID- 26378554 TI - Environmental Restrictors to Occupational Participation in Old Age: Exploring Differences across Gender in Puerto Rico. AB - Many older adults face challenges that prevent them from accomplishing common daily activities such as moving around, home maintenance, and leisure activities. There is still a need to examine and understand how environmental factors impact daily participation across gender. This study sought to make a qualitative comparison of gender differences regarding environmental barriers to participation in daily occupations from the perspectives of older adults who live alone in Puerto Rico. Twenty-six Hispanic older adults, 70 years or older participated in this study. We used a descriptive qualitative research design in which researchers administered an in-depth interview to each participant. The results elucidated that women were more likely than men to experience restricted participation due to lack of accessibility of the built environment and transportation systems. The findings could help with the development of tailored, occupation-based, preventive interventions that address gender specific environmental barriers and promote greater participation among both women and men. Further research is required to explore whether these environmental barriers to occupational participation remain consistent across living situations, socioeconomic status and ethnicity. PMID- 26378555 TI - Factors Influencing Self-Management in Chinese Adults with Type 2 Diabetes: A Systematic Review and Meta-Analysis. AB - Diabetes is a major public health problem in China. Diabetes self-management is critical for patients to achieved better health outcomes, however, previous studies have shown suboptimal diabetes self-management performance. We conducted a systematic review and meta-analysis to identify factors associated with diabetes self-management in Chinese adults. The results showed that confrontation, resignation, overall health beliefs, perceived susceptibility, perceived barriers, and self-efficacy were factors associated with overall diabetes self-management performance and six aspects of diabetes self-management behaviors. There is some limited evidence to suggest that provider-patient communication, married individuals, higher educational level, and higher household income level may also be linked to better diabetes self-management practice. Having healthcare insurance and utilizing chronic illness resources generally appeared to have a favorable effect on diabetes self-management performance. In addition, there were a number of factors for which the evidence is too limited to be able to ascertain its strength of association with diabetes self-management practice. The findings of this review suggest that diabetes self management behaviors are affected by a wide range of personal and environmental factors, which allow health care providers to develop theory-based strategies to improve diabetes-self-management behaviors in this population. PMID- 26378556 TI - Health and Quality of Life Perception in Older Adults: The Joint Role of Cognitive Efficiency and Functional Mobility. AB - Cognitive and mobility functions are involved in health-related quality of life (HRQoL). The present cross-sectional study aimed at investigating what facets of efficient cognition and functional mobility interactively contribute to mental and physical HRQoL. Fifty-six healthy older individuals (aged 65-75 years) were evaluated for mental and physical HRQoL, core cognitive executive functions (inhibition, working memory, and cognitive flexibility), and functional mobility (walking) under single and dual task conditions. Multiple regression analyses were run to verify which core executive functions predicted mental and physical HRQoL and whether the ability to perform complex (dual) walking tasks moderated such association. Inhibitory efficiency and the ability to perform physical mental dual tasks interactively predicted mental HRQoL, whereas cognitive flexibility and the ability to perform physical dual tasks interactively predicted physical HRQoL. Different core executive functions seem relevant for mental and physical HRQoL. Executive function efficiency seems to translate into HRQoL perception when coupled with tangible experience of the ability to walk under dual task conditions that mirror everyday life demands. Implications of these results for supporting the perception of mental and physical quality of life at advanced age are discussed, suggesting the usefulness of multicomponent interventions and environments conducive to walking that jointly aid successful cognitive aging and functional mobility. PMID- 26378557 TI - Identification of Response Options to Artisanal and Small-Scale Gold Mining (ASGM) in Ghana via the Delphi Process. AB - The Delphi technique is a means of facilitating discussion among experts in order to develop consensus, and can be used for policy formulation. This article describes a modified Delphi approach in which 27 multi-disciplinary academics and 22 stakeholders from Ghana and North America were polled about ways to address negative effects of small-scale gold mining (ASGM) in Ghana. In early 2014, the academics, working in disciplinary groups, synthesized 17 response options based on data aggregated during an Integrated Assessment of ASGM in Ghana. The researchers participated in two rounds of Delphi polling in March and April 2014, during which 17 options were condensed into 12. Response options were rated via a 4-point Likert scale in terms of benefit (economic, environmental, and benefit to people) and feasibility (economic, social/cultural, political, and implementation). The six highest-scoring options populated a third Delphi poll, which 22 stakeholders from diverse sectors completed in April 2015. The academics and stakeholders also prioritized the response options using ranking exercises. The technique successfully gauged expert opinion on ASGM, and helped identify potential responses, policies and solutions for the sector. This is timely given that improvement to the ASGM sector is an important component within the UN Minamata Convention. PMID- 26378558 TI - Factors Associated with Community Participation among Individuals Who Have Experienced Homelessness. AB - Community participation is an important goal for people who have experienced homelessness. The aim of this study was to use the International Classification of Functioning, Disability and Health (ICF) as a framework to examine factors associated with community participation among people who are homeless or recently housed through housing programs. Participants (n = 120) recruited from six housing placement and search programs completed measures of community participation (including productivity, social and leisure, and community-services use domains), psychiatric and physical symptoms, functional limitations, and a demographic form. Multiple regression analyses were used to identify predictors of overall community participation and subdomain scores. Results suggested that cognitive and mobility limitations, relationship status, and housing status significantly predicted both overall participation and participation in productivity and social and leisure subdomains. Participants who were housed through housing programs, who had cognitive and mobility limitations, and who were single showed less community participation. The findings suggest that activity limitations and environmental and personal factors may need to be addressed in efforts to enhance community participation in this population. PMID- 26378559 TI - Improving Personal Characterization of Meaningful Activity in Adults with Chronic Conditions Living in a Low-Income Housing Community. AB - PURPOSE: To understand how adults living in a low-income, public housing community characterize meaningful activity (activity that gives life purpose) and if through short-term intervention, could overcome identified individual and environmental barriers to activity engagement. METHODS: We used a mixed methods design where Phase 1 (qualitative) informed the development of Phase 2 (quantitative). Focus groups were conducted with residents of two low-income, public housing communities to understand their characterization of meaningful activity and health. From these results, we developed a theory-based group intervention for overcoming barriers to engagement in meaningful activity. Finally, we examined change in self-report scores from the Meaningful Activity Participation Assessment (MAPA) and the Engagement in Meaningful Activity Survey (EMAS). RESULTS: Health literacy appeared to impact understanding of the questions in Phase 1. Activity availability, transportation, income and functional limitations were reported as barriers to meaningful activity. Phase 2 within group analysis revealed a significant difference in MAPA pre-post scores (p =0.007), but not EMAS (p =0.33). DISCUSSION: Health literacy should be assessed and addressed in this population prior to intervention. After a group intervention, participants had a change in characterization of what is considered healthy, meaningful activity but reported fewer changes to how their activities aligned with their values. PMID- 26378560 TI - Impact of Cadmium Exposure on the Association between Lipopolysaccharide and Metabolic Syndrome. AB - Cadmium (Cd) is an environmental contaminant that has a direct impact on the gut microbiome. Perturbations in the gut microbiome have been linked to metabolic disorders associated with inflammation generated by lipopolysaccharide (LPS). We investigated the impact of Cd on the association between LPS and metabolic syndrome. The study population consisted of 200 apparently healthy subjects (30 64 years of age; 96 men, 104 women). Serum LPS and blood Cd concentrations were measured by ELISA and graphite furnace-atomic absorption spectrophotometry (GF AAS), respectively. The highest LPS quartile was associated with a greater prevalence of metabolic syndrome in men. There was a significant association between LPS activity and metabolic syndrome in men with blood Cd concentrations higher than the 50th percentile (OR = 3.05, 95% CI = 1.39-6.70); however, this relationship was not significant in men with blood Cd concentrations lower than the 50th percentile. The results of this study provide evidence for a strong association between high LPS activity and the prevalence of metabolic syndrome in men with relatively high blood Cd concentrations. Therefore, exposure to Cd may potentiate the association between LPS and metabolic syndrome in men. PMID- 26378561 TI - An Evaluation on the Effect of Health Education and of Low-Dose Statin in Dyslipidemia among Low-Income Rural Uyghur Adults in Far Western China: A Comprehensive Intervention Study. AB - OBJECTIVE: To evaluate the effect of comprehensive intervention by health education and medical intervention to dyslipidemia Uyghur patients in low-income rural areas in Xinjiang, China. METHOD: A multistaged (prefecture-county-township village) stratified cluster random sampling method was used to select participants in southern Xinjiang. Twelve villages in Jiangbazi Township in Jiashi County were chosen. These villages were randomly divided into six intervention groups and six control groups, and local Uyghur aged 18 years or older residing in the village for at least 6 months were interviewed for a baseline prevalence study and to select participants for two years of comprehensive intervention including low dose simvastatin and the effects of the interventions were observed. RESULTS: A total of 655 participants (347 participants in the intervention groups, 308 participants in the control groups) were randomly selected from 12 villages in Jiangbazi Township, follow-up rate is 87.0%. Compared to baseline mean levels of TG and LDL-C were reduced by 1.39 mmol/L (p < 0.01) and 2.12 mmol/L (p < 0.01) respectively and levels of HDL-C increased by1.22 mmol/L (p < 0.01) in the intervention group. Lipids were controlled in 38.61% of the intervention groups vs. 3.57% of the control groups (p < 0.01). Compared with baseline lipid levels, TG, TC, LDL-C and HDL-C was significantly improved, compared with it was in control groups. CONCLUSIONS: Blood lipid levels of Uygur patients with dyslipidemia can be effectively improved through health education combined with low-dose statin administration. This suggests that national strategies in public health be developed to improve the treatments to low-income rural minorities with dyslipidemia. PMID- 26378562 TI - Fire Blight Control: The Struggle Goes On. A Comparison of Different Fire Blight Control Methods in Switzerland with Respect to Biosafety, Efficacy and Durability. AB - Fire blight (FB), caused by Erwinia amylovora, is one of the most important pome fruit pathogens worldwide. To control this devastating disease, various chemical and biological treatments are commonly applied in Switzerland, but they fail to keep the infection at an acceptable level in years of heavy disease pressure. The Swiss authorities therefore currently allow the controlled use of the antibiotic streptomycin against FB in years that are predicted to have heavy infection periods, but only one treatment per season is permitted. Another strategy for controlling Erwinia is to breed resistant/tolerant apple cultivars. One way of accelerating the breeding process is to obtain resistant cultivars by inserting one or several major resistance genes, using genetic engineering. To date, no study summarizing the impact of different FB control measures on the environment and on human health has been performed. This study consequently aims to compare different disease-control measures (biological control, chemical control, control by antibiotics and by resistant/tolerant apple cultivars obtained through conventional or molecular breeding) applied against E. amylovora, considering different protection goals (protection of human health, environment, agricultural diversity and economic interest), with special emphasis on biosafety aspects. Information on each FB control measure in relation to the specified protection goal was assessed by literature searches and by interviews with experts. Based on our results it can be concluded that the FB control measures currently applied in Switzerland are safe for consumers, workers and the environment. However, there are several gaps in our knowledge of the human health and environmental impacts analyzed: data are missing (1) on long term studies on the efficacy of most of the analyzed FB control measures; (2) on the safety of operators handling streptomycin; (3) on residue analyses of Equisetum plant extract, the copper and aluminum compounds used in apple production; and (4) on the effect of biological and chemical control measures on non-target fauna and flora. These gaps urgently need to be addressed in the near future. PMID- 26378563 TI - Ecological Risk of Heavy Metals and a Metalloid in Agricultural Soils in Tarkwa, Ghana. AB - Heavy metals and a metalloid in agricultural soils in 19 communities in Tarkwa were analyzed to assess the potential ecological risk. A total of 147 soil samples were collected in June, 2012 and analyzed for As, Cd, Co, Cr, Cu, Hg, Ni, Pb and Zn. Mean concentrations (mg/kg dw) of heavy metals in the communities decreased in order of Zn (39) ? Cr (21) ? Pb (7.2) ? Cu (6.2) ? As (4.4) ? Ni (3.7) ? Co (1.8) ? Hg (0.32) ? Cd (0.050). Correlations among heavy metals and soil properties indicated that soil organic matter could have substantial influence on the total contents of these metals in soil. From the results, integrated pollution (C(deg)) in some communities such as, Wangarakrom (11), Badukrom (13) and T-Tamso (17) indicated high pollution with toxic metals, especially from As and Hg. Potential ecological risk (RI) indices indicated low (Mile 7) to high risks (Wangarakrom; Badukrom) of metals. Based on pollution coefficient (C(i)(f)), C(deg), monomial ecological risk (E(i)(r)) and RI, the investigated soils fall within low to high contamination and risk of heavy metals to the ecological system especially plants, soil invertebrates and/or mammalian wildlife. This represented moderate potential ecological risk in the study area, and mining activities have played a significant role. PMID- 26378564 TI - Associations among Human-Associated Fecal Contamination, Microcystis aeruginosa, and Microcystin at Lake Erie Beaches. AB - Lake Erie beaches exhibit impaired water quality due to fecal contamination and cyanobacterial blooms, though few studies address potential relationships between these two public health hazards. Using quantitative polymerase chain reaction (qPCR), Microcystis aeruginosa was monitored in conjunction with a human associated fecal marker (Bacteroides fragilis group; g-Bfra), microcystin, and water quality parameters at two beaches to evaluate their potential associations. During the summer of 2010, water samples were collected 32 times from both Euclid and Villa Angela beaches. The phycocyanin intergenic spacer (PC-IGS) and the microcystin-producing (mcyA) gene in M. aeruginosa were quantified with qPCR. PC IGS and mcyA were detected in 50.0% and 39.1% of samples, respectively, and showed increased occurrences after mid-August. Correlation and regression analyses showed that water temperature was negatively correlated with M. aeruginosa markers and microcystin. The densities of mcyA and the g-Bfra were predicted by nitrate, implicating fecal contamination as contributing to the growth of M. aeruginosa by nitrate loading. Microcystin was correlated with mcyA (r = 0.413, p < 0.01), suggesting toxin-producing M. aeruginosa populations may significantly contribute to microcystin production. Additionally, microcystin was correlated with total phosphorus (r = 0.628, p < 0.001), which was higher at Euclid (p < 0.05), possibly contributing to higher microcystin concentrations at Euclid. PMID- 26378565 TI - Immersive Virtual Environment Technology to Supplement Environmental Perception, Preference and Behavior Research: A Review with Applications. AB - Immersive virtual environment (IVE) technology offers a wide range of potential benefits to research focused on understanding how individuals perceive and respond to built and natural environments. In an effort to broaden awareness and use of IVE technology in perception, preference and behavior research, this review paper describes how IVE technology can be used to complement more traditional methods commonly applied in public health research. The paper also describes a relatively simple workflow for creating and displaying 360 degrees virtual environments of built and natural settings and presents two freely available and customizable applications that scientists from a variety of disciplines, including public health, can use to advance their research into human preferences, perceptions and behaviors related to built and natural settings. PMID- 26378566 TI - Suicide Communication on Social Media and Its Psychological Mechanisms: An Examination of Chinese Microblog Users. AB - BACKGROUND: This study aims to examine the characteristics of people who talk about suicide on Chinese microblogs (referred to as Weibo suicide communication (WSC)), and the psychological antecedents of such behaviors. METHODS: An online survey was conducted on Weibo users. Differences in psychological and social demographic characteristics between those who exhibited WSC and those who did not were examined. Three theoretical models were proposed to explain the psychological mechanisms of WSC and their fitness was examined by Structural Equation Modeling (SEM). RESULTS: 12.03% of our respondents exhibited WSC in the past 12 months. The WSC group was significantly younger and less educated, preferred using blogs and online forums for expressing themselves, and reported significantly greater suicide ideation, negative affectivity, and vulnerable personality compared to non-WSC users. SEM examinations found that Weibo users with higher negative affectivity or/and suicidal ideation, who were also using blogs and forums more, exhibited a significantly higher possibility of WSC. CONCLUSION: Weibo users who are at greater suicide risk are more likely to talk about suicide on Weibo. WSC is a sign of negative affectivity or suicide ideation, and should be responded to with emotional support and suicide prevention services. PMID- 26378567 TI - Honokiol, a Lignan Biphenol Derived from the Magnolia Tree, Inhibits Dengue Virus Type 2 Infection. AB - Dengue is the most widespread arbovirus infection and poses a serious health and economic issue in tropical and subtropical countries. Currently no licensed vaccine or compounds can be used to prevent or manage the severity of dengue virus (DENV) infection. Honokiol, a lignan biphenol derived from the Magnolia tree, is commonly used in Eastern medicine. Here we report that honokiol has profound antiviral activity against serotype 2 DENV (DENV-2). In addition to inhibiting the intracellular DENV-2 replicon, honokiol was shown to suppress the replication of DENV-2 in baby hamster kidney (BHK) and human hepatocarcinoma Huh7 cells. At the maximum non-toxic dose of honokiol treatment, the production of infectious DENV particles was reduced >90% in BHK and Huh7 cells. The underlying mechanisms revealed that the expression of DENV-2 nonstructural protein NS1/NS3 and its replicating intermediate, double-strand RNA, was dramatically reduced by honokiol treatment. Honokiol has no effect on the expression of DENV putative receptors, but may interfere with the endocytosis of DENV-2 by abrogating the co localization of DENV envelope glycoprotein and the early endosomes. These results indicate that honokiol inhibits the replication, viral gene expression, and endocytotic process of DENV-2, making it a promising agent for chemotherapy of DENV infection. PMID- 26378569 TI - Structural and Antihypertensive Properties of Enzymatic Hemp Seed Protein Hydrolysates. AB - The aim of this work was to produce antihypertensive protein hydrolysates through different forms of enzymatic hydrolysis (2% pepsin, 4% pepsin, 1% alcalase, 2% alcalase, 2% papain, and 2% pepsin + pancreatin) of hemp seed proteins (HSP). The hemp seed protein hydrolysates (HPHs) were tested for in vitro inhibitions of renin and angiotensin-converting enzyme (ACE), two of the enzymes that regulate human blood pressure. The HPHs were then administered orally (200 mg/kg body weight) to spontaneously hypertensive rats and systolic blood pressure (SBP) lowering effects measured over a 24 h period. Size exclusion chromatography mainly showed a 300-9560 Da peptide size range for the HPHs, while amino acid composition data had the 2% pepsin HPH with the highest cysteine content. Fluorescence spectroscopy revealed higher fluorescence intensities for the peptides when compared to the unhydrolyzed hemp seed protein. Overall, the 1% alcalase HPH was the most effective (p < 0.05) SBP-reducing agent (-32.5 +/- 0.7 mmHg after 4 h), while the pepsin HPHs produced longer-lasting effects (-23.0 +/- 1.4 mmHg after 24 h). We conclude that an optimized combination of the fast acting HPH (1% alcalase) with the longer-lasting HPHs (2% and 4% pepsin) could provide daily effective SBP reductions. PMID- 26378568 TI - Insect-Specific Virus Discovery: Significance for the Arbovirus Community. AB - Arthropod-borne viruses (arboviruses), especially those transmitted by mosquitoes, are a significant cause of morbidity and mortality in humans and animals worldwide. Recent discoveries indicate that mosquitoes are naturally infected with a wide range of other viruses, many within taxa occupied by arboviruses that are considered insect-specific. Over the past ten years there has been a dramatic increase in the literature describing novel insect-specific virus detection in mosquitoes, which has provided new insights about viral diversity and evolution, including that of arboviruses. It has also raised questions about what effects the mosquito virome has on arbovirus transmission. Additionally, the discovery of these new viruses has generated interest in their potential use as biological control agents as well as novel vaccine platforms. The arbovirus community will benefit from the growing database of knowledge concerning these newly described viral endosymbionts, as their impacts will likely be far reaching. PMID- 26378570 TI - Explaining Vegetable Consumption among Young Adults: An Application of the Theory of Planned Behaviour. AB - Although fruit and vegetable consumption is highly recommended for a healthy and balanced daily diet, several European countries do not meet these recommendations. In Italy, only 45% of young people are consuming at least one portion of vegetables per day. Therefore, this paper aims to understand the main determinants of vegetables consumption among young adults to suggest possible intervention strategies. A cross-sectional study was conducted on a samples of Italian students (n = 751), using the theory of planned behaviour (TPB) as a conceptual framework. A structural equation model (SEM) was developed to test the TPB predictors for vegetable consumption, and the role of background factors (socio-demographic and personal characteristics) in improving the TPB model's explaining power. Overall, 81% and 68%, respectively, of intentions and behaviour variance is explained by the TPB model. Socio-demographic and personal characteristics were found to influence intentions and behaviour indirectly by their effects on the theory's more proximal determinants. Interventions should be targeted to improve perceived behavioural control (PBC), attitudes and subjective norms that significantly affect intentions. Tailored interventions for male students, enrolled in courses other than food science, and doing less physical activity may have a larger effect on behavioural change. PMID- 26378571 TI - Effects of Olive Oil on Markers of Inflammation and Endothelial Function-A Systematic Review and Meta-Analysis. AB - The aim of the present systematic review was to synthesize data from randomized controlled trials investigating the effects of olive oil on markers of inflammation or endothelial function. Literature search in electronic databases Cochrane Trial Register, EMBASE, and MEDLINE was performed. Thirty studies enrolling 3106 participants fulfilled the selection criteria. Pooled effects of different interventions were assessed as mean difference using a random effects model. Olive oil interventions (with daily consumption ranging approximately between 1 mg and 50 mg) resulted in a significantly more pronounced decrease in C reactive protein (mean difference: -0.64 mg/L, (95% confidence interval (CI) 0.96 to -0.31), p < 0.0001, n = 15 trials) and interleukin-6 (mean difference: 0.29 (95% CI -0.7 to -0.02), p < 0.04, n = 7 trials) as compared to controls, respectively. Values of flow-mediated dilatation (given as absolute percentage) were significantly more increased in individuals subjected to olive oil interventions (mean difference: 0.76% (95% CI 0.27 to 1.24), p < 0.002, n = 8 trials). These results provide evidence that olive oil might exert beneficial effects on endothelial function as well as markers of inflammation and endothelial function, thus representing a key ingredient contributing to the cardiovascular-protective effects of a Mediterranean diet. However, due to the heterogeneous study designs (e.g., olive oil given as a supplement or as part of dietary pattern, variations in control diets), a conservative interpretation of the results is necessary. PMID- 26378572 TI - Increased PUFA Content and 5-Lipoxygenase Pathway Expression Are Associated with Subcutaneous Adipose Tissue Inflammation in Obese Women with Type 2 Diabetes. AB - Obese women with type 2 diabetes mellitus (T2DM) have more inflammation in their subcutaneous white adipose tissue (sWAT) than age-and-BMI similar obese women with normal glucose tolerance (NGT). We aimed to investigate whether WAT fatty acids and/or oxylipins are associated with the enhanced inflammatory state in WAT of the T2DM women. Fatty acid profiles were measured in both subcutaneous and visceral adipose tissue (vWAT) of 19 obese women with NGT and 16 age-and-BMI similar women with T2DM. Oxylipin levels were measured in sWAT of all women. Arachidonic acid (AA) and docosahexaenoic acid (DHA) percentages were higher in sWAT, but not vWAT of the T2DM women, and AA correlated positively to the gene expression of macrophage marker CD68. We found tendencies for higher oxylipin concentrations of the 5-LOX leukotrienes in sWAT of T2DM women. Gene expression of the 5-LOX leukotriene biosynthesis pathway was significantly higher in sWAT of T2DM women. In conclusion, AA and DHA content were higher in sWAT of T2DM women and AA correlated to the increased inflammatory state in sWAT. Increased AA content was accompanied by an upregulation of the 5-LOX pathway and seems to have led to an increase in the conversion of AA into proinflammatory leukotrienes in sWAT. PMID- 26378573 TI - Green and Black Cardamom in a Diet-Induced Rat Model of Metabolic Syndrome. AB - Both black (B) and green (G) cardamom are used as flavours during food preparation. This study investigated the responses to B and G in a diet-induced rat model of human metabolic syndrome. Male Wistar rats were fed either a corn starch-rich diet (C) or a high-carbohydrate, high-fat diet with increased simple sugars along with saturated and trans fats (H) for 16 weeks. H rats showed signs of metabolic syndrome leading to visceral obesity with hypertension, glucose intolerance, cardiovascular remodelling and nonalcoholic fatty liver disease. Food was supplemented with 3% dried B or G for the final eight weeks only. The major volatile components were the closely related terpenes, 1,8-cineole in B and alpha-terpinyl acetate in G. HB (high-carbohydrate, high-fat + black cardamom) rats showed marked reversal of diet-induced changes, with decreased visceral adiposity, total body fat mass, systolic blood pressure and plasma triglycerides, and structure and function of the heart and liver. In contrast, HG (high carbohydrate, high-fat + green cardamom) rats increased visceral adiposity and total body fat mass, and increased heart and liver damage, without consistent improvement in the signs of metabolic syndrome. These results suggest that black cardamom is more effective in reversing the signs of metabolic syndrome than green cardamom. PMID- 26378574 TI - Polyphenolic Composition of Crataegus monogyna Jacq.: From Chemistry to Medical Applications. AB - The abundance of scientific evidence has shown that many synthetic drugs can cause serious adverse effects in patients. Recently, the search of natural therapeutic agents with low adverse effects has attracted much attention. In particular, considerable interest has focused on edible and medicinal plants, which play an important role in human diet, and have been used for disease treatment since ancient times. Crataegus monogyna Jacq. (hawthorn) is one of the most important edible plants of the Rosaceae family and is also used in traditional medicine. Growing evidence has shown that this plant has various interesting physiological and pharmacological activities due to the presence of different bioactive natural compounds. In addition, scientific evidence suggests that the toxicity of hawthorn is negligible. Therefore, the aim of this paper is to provide a critical review of the available scientific literature about pharmacological activities as well as botanical aspects, phytochemistry and clinical impacts of C. monogyna. PMID- 26378575 TI - Antibacterial Effects of Cinnamon: From Farm to Food, Cosmetic and Pharmaceutical Industries. AB - Herbs and spices have been used since ancient times, because of their antimicrobial properties increasing the safety and shelf life of food products by acting against foodborne pathogens and spoilage bacteria. Plants have historically been used in traditional medicine as sources of natural antimicrobial substances for the treatment of infectious disease. Therefore, much attention has been paid to medicinal plants as a source of alternative antimicrobial strategies. Moreover, due to the growing demand for preservative free cosmetics, herbal extracts with antimicrobial activity have recently been used in the cosmetic industry to reduce the risk of allergies connected to the presence of methylparabens. Some species belonging to the genus Cinnamomum, commonly used as spices, contain many antibacterial compounds. This paper reviews the literature published over the last five years regarding the antibacterial effects of cinnamon. In addition, a brief summary of the history, traditional uses, phytochemical constituents, and clinical impact of cinnamon is provided. PMID- 26378576 TI - Milk Consumption and Mortality from All Causes, Cardiovascular Disease, and Cancer: A Systematic Review and Meta-Analysis. AB - Results from epidemiological studies of milk consumption and mortality are inconsistent. We conducted a systematic review and meta-analysis of prospective studies assessing the association of non-fermented and fermented milk consumption with mortality from all causes, cardiovascular disease, and cancer. PubMed was searched until August 2015. A two-stage, random-effects, dose-response meta analysis was used to combine study-specific results. Heterogeneity among studies was assessed with the I2 statistic. During follow-up periods ranging from 4.1 to 25 years, 70,743 deaths occurred among 367,505 participants. The range of non fermented and fermented milk consumption and the shape of the associations between milk consumption and mortality differed considerably between studies. There was substantial heterogeneity among studies of non-fermented milk consumption in relation to mortality from all causes (12 studies; I2 = 94%), cardiovascular disease (five studies; I2 = 93%), and cancer (four studies; I2 = 75%) as well as among studies of fermented milk consumption and all-cause mortality (seven studies; I2 = 88%). Thus, estimating pooled hazard ratios was not appropriate. Heterogeneity among studies was observed in most subgroups defined by sex, country, and study quality. In conclusion, we observed no consistent association between milk consumption and all-cause or cause-specific mortality. PMID- 26378578 TI - Ochratoxin A Dietary Exposure of Ten Population Groups in the Czech Republic: Comparison with Data over the World. AB - Ochratoxin A is a nephrotoxic and renal carcinogenic mycotoxin and is a common contaminant of various food commodities. Eighty six kinds of foodstuffs (1032 food samples) were collected in 2011-2013. High-performance liquid chromatography with fluorescence detection was used for ochratoxin A determination. Limit of quantification of the method varied between 0.01-0.2 MUg/kg depending on the food matrices. The most exposed population is children aged 4-6 years old. Globally for this group, the maximum ochratoxin A dietary exposure for "average consumer" was estimated at 3.3 ng/kg bw/day (lower bound, considering the analytical values below the limit of quantification as 0) and 3.9 ng/kg bw/day (middle bound, considering the analytical values below the limit of quantification as 1/2 limit of quantification). Important sources of exposure for this latter group include grain-based products, confectionery, meat products and fruit juice. The dietary intake for "high consumers" in the group 4-6 years old was estimated from grains and grain-based products at 19.8 ng/kg bw/day (middle bound), from tea at 12.0 ng/kg bw/day (middle bound) and from confectionery at 6.5 ng/kg bw/day (middle bound). For men aged 18-59 years old beer was the main contributor with an intake of 2.60 ng/kg bw/day ("high consumers", middle bound). Tea and grain-based products were identified to be the main contributors for dietary exposure in women aged 18-59 years old. Coffee and wine were identified as a higher contributor of the OTA intake in the population group of women aged 18-59 years old compared to the other population groups. PMID- 26378577 TI - Evolution of Chemical Diversity in a Group of Non-Reduced Polyketide Gene Clusters: Using Phylogenetics to Inform the Search for Novel Fungal Natural Products. AB - Fungal polyketides are a diverse class of natural products, or secondary metabolites (SMs), with a wide range of bioactivities often associated with toxicity. Here, we focus on a group of non-reducing polyketide synthases (NR PKSs) in the fungal phylum Ascomycota that lack a thioesterase domain for product release, group V. Although widespread in ascomycete taxa, this group of NR-PKSs is notably absent in the mycotoxigenic genus Fusarium and, surprisingly, found in genera not known for their secondary metabolite production (e.g., the mycorrhizal genus Oidiodendron, the powdery mildew genus Blumeria, and the causative agent of white-nose syndrome in bats, Pseudogymnoascus destructans). This group of NR PKSs, in association with the other enzymes encoded by their gene clusters, produces a variety of different chemical classes including naphthacenediones, anthraquinones, benzophenones, grisandienes, and diphenyl ethers. We discuss the modification of and transitions between these chemical classes, the requisite enzymes, and the evolution of the SM gene clusters that encode them. Integrating this information, we predict the likely products of related but uncharacterized SM clusters, and we speculate upon the utility of these classes of SMs as virulence factors or chemical defenses to various plant, animal, and insect pathogens, as well as mutualistic fungi. PMID- 26378579 TI - Quantitative Analysis of Staphylococcal Enterotoxins A and B in Food Matrices Using Ultra High-Performance Liquid Chromatography Tandem Mass Spectrometry (UPLC MS/MS). AB - A method that uses mass spectrometry (MS) for identification and quantification of protein toxins, staphylococcal enterotoxins A and B (SEA and SEB), in milk and shrimp is described. The analysis was performed using a tryptic peptide, from each of the toxins, as the target analyte together with the corresponding (13)C labeled synthetic internal standard peptide. The performance of the method was evaluated by analyzing spiked samples in the quantification range 2.5-30 ng/g (R2 = 0.92-0.99). The limit of quantification (LOQ) in milk and the limit of detection (LOD) in shrimp was 2.5 ng/g, for both SEA and SEB toxins. The in-house reproducibility (RSD) was 8%-30% and 5%-41% at different concentrations for milk and shrimp, respectively. The method was compared to the ELISA method, used at the EU-RL (France), for milk samples spiked with SEA at low levels, in the quantification range of 2.5 to 5 ng/g. The comparison showed good coherence for the two methods: 2.9 (MS)/1.8 (ELISA) and 3.6 (MS)/3.8 (ELISA) ng/g. The major advantage of the developed method is that it allows direct confirmation of the molecular identity and quantitative analysis of SEA and SEB at low nanogram levels using a label and antibody free approach. Therefore, this method is an important step in the development of alternatives to the immune-assay tests currently used for staphylococcal enterotoxin analysis. PMID- 26378580 TI - Open Field Study of Some Zea mays Hybrids, Lipid Compounds and Fumonisins Accumulation. AB - Lipid molecules are increasingly recognized as signals exchanged by organisms interacting in pathogenic and/or symbiotic ways. Some classes of lipids actively determine the fate of the interactions. Host cuticle/cell wall/membrane components such as sphingolipids and oxylipins may contribute to determining the fate of host-pathogen interactions. In the present field study, we considered the relationship between specific sphingolipids and oxylipins of different hybrids of Zea mays and fumonisin by F. verticillioides, sampling ears at different growth stages from early dough to fully ripe. The amount of total and free fumonisin differed significantly between hybrids and increased significantly with maize ripening. Oxylipins and phytoceramides changed significantly within the hybrids and decreased with kernel maturation, starting from physiological maturity. Although the correlation between fumonisin accumulation and plant lipid profile is certain, the data collected so far cannot define a cause-effect relationship but open up new perspectives. Therefore, the question-"Does fumonisin alter plant lipidome or does plant lipidome modulate fumonisin accumulation?"-is still open. PMID- 26378581 TI - Exploration of Deregulated Long Non-Coding RNAs in Association with Hepatocarcinogenesis and Survival. AB - Long non-coding RNAs (lncRNAs) are larger than 200 nucleotides in length and pervasively expressed across the genome. An increasing number of studies indicate that lncRNA transcripts play integral regulatory roles in cellular growth, division, differentiation and apoptosis. Deregulated lncRNAs have been observed in a variety of human cancers, including hepatocellular carcinoma (HCC). We determined the expression profiles of 90 lncRNAs for 65 paired HCC tumor and adjacent non-tumor tissues, and 55 lncRNAs were expressed in over 90% of samples. Eight lncRNAs were significantly down-regulated in HCC tumor compared to non tumor tissues (p < 0.05), but no lncRNA achieved statistical significance after Bonferroni correction for multiple comparisons. Within tumor tissues, carrying more aberrant lncRNAs (6-7) was associated with a borderline significant reduction Cancers 2015, 7 1848 in survival (HR = 8.5, 95% CI: 1.0-72.5). The predictive accuracy depicted by the AUC was 0.93 for HCC survival when using seven deregulated lncRNAs (likelihood ratio test p = 0.001), which was similar to that combining the seven lncRNAs with tumor size and treatment (AUC = 0.96, sensitivity = 87%, specificity = 87%). These data suggest the potential association of deregulated lncRNAs with hepatocarcinogenesis and HCC survival. PMID- 26378582 TI - Nephron Patterning: Lessons from Xenopus, Zebrafish, and Mouse Studies. AB - The nephron is the basic structural and functional unit of the vertebrate kidney. To ensure kidney functions, the nephrons possess a highly segmental organization where each segment is specialized for the secretion and reabsorption of particular solutes. During embryogenesis, nephron progenitors undergo a mesenchymal-to-epithelial transition (MET) and acquire different segment-specific cell fates along the proximo-distal axis of the nephron. Even if the morphological changes occurring during nephrogenesis are characterized, the regulatory networks driving nephron segmentation are still poorly understood. Interestingly, several studies have shown that the pronephric nephrons in Xenopus and zebrafish are segmented in a similar fashion as the mouse metanephric nephrons. Here we review functional and molecular aspects of nephron segmentation with a particular interest on the signaling molecules and transcription factors recently implicated in kidney development in these three different vertebrate model organisms. A complete understanding of the mechanisms underlying nephrogenesis in different model organisms will provide novel insights on the etiology of several human renal diseases. PMID- 26378583 TI - Specialized Cilia in Mammalian Sensory Systems. AB - Cilia and flagella are highly conserved and important microtubule-based organelles that project from the surface of eukaryotic cells and act as antennae to sense extracellular signals. Moreover, cilia have emerged as key players in numerous physiological, developmental, and sensory processes such as hearing, olfaction, and photoreception. Genetic defects in ciliary proteins responsible for cilia formation, maintenance, or function underlie a wide array of human diseases like deafness, anosmia, and retinal degeneration in sensory systems. Impairment of more than one sensory organ results in numerous syndromic ciliary disorders like the autosomal recessive genetic diseases Bardet-Biedl and Usher syndrome. Here we describe the structure and distinct functional roles of cilia in sensory organs like the inner ear, the olfactory epithelium, and the retina of the mouse. The spectrum of ciliary function in fundamental cellular processes highlights the importance of elucidating ciliopathy-related proteins in order to find novel potential therapies. PMID- 26378584 TI - Replication Stress: A Lifetime of Epigenetic Change. AB - DNA replication is essential for cell division. Challenges to the progression of DNA polymerase can result in replication stress, promoting the stalling and ultimately collapse of replication forks. The latter involves the formation of DNA double-strand breaks (DSBs) and has been linked to both genome instability and irreversible cell cycle arrest (senescence). Recent technological advances have elucidated many of the factors that contribute to the sensing and repair of stalled or broken replication forks. In addition to bona fide repair factors, these efforts highlight a range of chromatin-associated changes at and near sites of replication stress, suggesting defects in epigenome maintenance as a potential outcome of aberrant DNA replication. Here, we will summarize recent insight into replication stress-induced chromatin-reorganization and will speculate on possible adverse effects for gene expression, nuclear integrity and, ultimately, cell function. PMID- 26378586 TI - Chitosan-Poly (I:C)-PADRE Based Nanoparticles as Delivery Vehicles for Synthetic Peptide Vaccines. AB - The safety and precision of peptide antigens has prompted the search for adjuvants capable of increasing the immune response against these intrinsically poorly immunogenic antigens. The integration of both immunostimulants and peptide antigens within nanometric delivery systems for their co-delivery to immune cells is a promising vaccination strategy. With this in mind, the potential synergistic effect of the immunostimulant poly (I:C) (pIC) and a T-Helper peptide (PADRE), integrated into a chitosan (CS) based nanostructure, was explored. The value of this nanostructured combination of materials was assessed for a peptide antigen (1338aa) derived from the HPV-16 L2 protein. These nanoparticles, produced by ionic gelation technique, exhibited a nanometric size (<300 nm), a high positive surface charge (>40 mV) and high pIC association efficiency (>96%). They also showed capacity for the association of both the 1338aa and PADRE peptides. The influence of the presence of pIC and PADRE in the nanocomposition, as well as that of the peptide presentation form (encapsulated versus surface adsorbed) on the antibody induction was evaluated in a preliminary in vivo study. The data obtained highlights the possibility to engineer nanoparticles through the rational combination of a number of adjuvant molecules together with the antigen. PMID- 26378585 TI - The Role of Indoleamine 2, 3-Dioxygenase in Immune Suppression and Autoimmunity. AB - Indoleamine 2, 3-dioxygenase (IDO) is the first and rate limiting catabolic enzyme in the degradation pathway of the essential amino acid tryptophan. By cleaving the aromatic indole ring of tryptophan, IDO initiates the production of a variety of tryptophan degradation products called "kynurenines" that are known to exert important immuno-regulatory functions. Because tryptophan must be supplied in the diet, regulation of tryptophan catabolism may exert profound effects by activating or inhibiting metabolism and immune responses. Important for survival, the regulation of IDO biosynthesis and its activity in cells of the immune system can critically alter their responses to immunological insults, such as infection, autoimmunity and cancer. In this review, we assess how IDO-mediated catabolism of tryptophan can modulate the immune system to arrest inflammation, suppress immunity to cancer and inhibit allergy, autoimmunity and the rejection of transplanted tissues. Finally, we examine how vaccines may enhance immune suppression of autoimmunity through the upregulation of IDO biosynthesis in human dendritic cells. PMID- 26378587 TI - Consequences of Ultra-Violet Irradiation on the Mechanical Properties of Spider Silk. AB - The outstanding combination of high tensile strength and extensibility of spider silk is believed to contribute to the material's toughness. Thus, there is great interest in engineering silk for biomedical products such as suture or implants. Additionally, over the years, many studies have also sought to enhance the mechanical properties of spider silk for wider applicability, e.g., by irradiating the material using ultra-violet radiation. However, the limitations surrounding the use of ultra-violet radiation for enhancing the mechanical properties of spider silk are not well-understood. Here, we have analyzed the mechanical properties of spider silk at short ultra-violet irradiation duration. Specimens of spider silk were subjected to ultra-violet irradiation (254-nm wavelength, i.e. UVC) for 10, 20, and 30 min, respectively, followed by tensile test to rupture to determine the strength (maximum stress), extensibility (rupture strain), and toughness (strain energy density to rupture). Controls, i.e., specimens that did not received UVC, were also subjected to tensile test to rupture to determine the respective mechanical properties. One-way analysis of variance reveals that these properties decrease significantly (p < 0.05) with increasing irradiation duration. Among the three mechanical parameters, the strength of the spider silk degrades most rapidly; the extensibility of the spider silk degrades the slowest. Overall, these changes correspond to the observed surface modifications as well as the bond rupture between the peptide chains of the treated silk. Altogether, this simple but comprehensive study provides some key insights into the dependence of the mechanical properties on ultra-violet irradiation duration. PMID- 26378589 TI - The Impact of Photobleaching on Microarray Analysis. AB - DNA-Microarrays have become a potent technology for high-throughput analysis of genetic regulation. However, the wide dynamic range of signal intensities of fluorophore-based microarrays exceeds the dynamic range of a single array scan by far, thus limiting the key benefit of microarray technology: parallelization. The implementation of multi-scan techniques represents a promising approach to overcome these limitations. These techniques are, in turn, limited by the fluorophores' susceptibility to photobleaching when exposed to the scanner's laser light. In this paper the photobleaching characteristics of cyanine-3 and cyanine-5 as part of solid state DNA microarrays are studied. The effects of initial fluorophore intensity as well as laser scanner dependent variables such as the photomultiplier tube's voltage on bleaching and imaging are investigated. The resulting data is used to develop a model capable of simulating the expected degree of signal intensity reduction caused by photobleaching for each fluorophore individually, allowing for the removal of photobleaching-induced, systematic bias in multi-scan procedures. Single-scan applications also benefit as they rely on pre-scans to determine the optimal scanner settings. These findings constitute a step towards standardization of microarray experiments and analysis and may help to increase the lab-to-lab comparability of microarray experiment results. PMID- 26378590 TI - Identifying the Tautomeric Form of a Deoxyguanosine-Estrogen Quinone Intermediate. AB - Mechanistic insights into the reaction of an estrogen o-quinone with deoxyguanosine has been further investigated using high level density functional calculations in addition to the use of 4-hyroxycatecholestrone (4-OHE1) regioselectivity labeled with deuterium at the C1-position. Calculations using the M06-2X functional with large basis sets indicate the tautomeric form of an estrogen-DNA adduct present when glycosidic bonds cleavage occurs is comprised of an aromatic A ring structure. This tautomeric form was further verified by use of deuterium labelling of the catechol precursor use to form the estrogen o-quinone. Regioselective deuterium labelling at the C1-position of the estrogen A ring allows discrimination between two tautomeric forms of a reaction intermediate either of which could be present during glycosidic bond cleavage. HPLC-MS analysis indicates a reactive intermediate with a m/z of 552.22 consistent with a tautomeric form containing no deuterium. This intermediate is consistent with a reaction mechanism that involves: (1) proton assisted Michael addition; (2) re aromatization of the estrogen A ring; and (3) glycosidic bond cleavage to form the known estrogen-DNA adduct, 4-OHE1-1-N7Gua. PMID- 26378588 TI - Substrates for Expansion of Corneal Endothelial Cells towards Bioengineering of Human Corneal Endothelium. AB - Corneal endothelium is a single layer of specialized cells that lines the posterior surface of cornea and maintains corneal hydration and corneal transparency essential for vision. Currently, transplantation is the only therapeutic option for diseases affecting the corneal endothelium. Transplantation of corneal endothelium, called endothelial keratoplasty, is widely used for corneal endothelial diseases. However, corneal transplantation is limited by global donor shortage. Therefore, there is a need to overcome the deficiency of sufficient donor corneal tissue. New approaches are being explored to engineer corneal tissues such that sufficient amount of corneal endothelium becomes available to offset the present shortage of functional cornea. Although human corneal endothelial cells have limited proliferative capacity in vivo, several laboratories have been successful in in vitro expansion of human corneal endothelial cells. Here we provide a comprehensive analysis of different substrates employed for in vitro cultivation of human corneal endothelial cells. Advances and emerging challenges with ex vivo cultured corneal endothelial layer for the ultimate goal of therapeutic replacement of dysfunctional corneal endothelium in humans with functional corneal endothelium are also presented. PMID- 26378591 TI - Integrating Multiple Analytical Datasets to Compare Metabolite Profiles of Mouse Colonic-Cecal Contents and Feces. AB - The pattern of metabolites produced by the gut microbiome comprises a phenotype indicative of the means by which that microbiome affects the gut. We characterized that phenotype in mice by conducting metabolomic analyses of the colonic-cecal contents, comparing that to the metabolite patterns of feces in order to determine the suitability of fecal specimens as proxies for assessing the metabolic impact of the gut microbiome. We detected a total of 270 low molecular weight metabolites in colonic-cecal contents and feces by gas chromatograph, time-of-flight mass spectrometry (GC-TOF) and ultra-high performance liquid chromatography, quadrapole time-of-flight mass spectrometry (UPLC-Q-TOF). Of that number, 251 (93%) were present in both types of specimen, representing almost all known biochemical pathways related to the amino acid, carbohydrate, energy, lipid, membrane transport, nucleotide, genetic information processing, and cancer-related metabolism. A total of 115 metabolites differed significantly in relative abundance between both colonic-cecal contents and feces. These data comprise the first characterization of relationships among metabolites present in the colonic-cecal contents and feces in a healthy mouse model, and shows that feces can be a useful proxy for assessing the pattern of metabolites to which the colonic mucosum is exposed. PMID- 26378593 TI - Investigation of Photovoltaic Properties of Single Core-Shell GaN/InGaN Wires. AB - We report the investigation of the photovoltaic properties of core-shell GaN/InGaN wires. The radial structure is grown on m-plane {1100} facets of self assembled c-axis GaN wires elaborated by metal-organic vapor phase epitaxy (MOVPE) on sapphire substrates. The conversion efficiency of wires with radial shell composed of thick In0.1Ga0.9N layers and of 30* In0.18Ga0.82N/GaN quantum wells are compared. We also investigate the impact of the contact nature and layout on the carrier collection and photovoltaic performances. The contact optimization results in an improved conversion efficiency of 0.33% and a fill factor of 83% under 1 sun (AM1.5G) on single wires with a quantum well-based active region. Photocurrent spectroscopy demonstrates that the response ascribed to the absorption of InGaN/GaN quantum wells appears at wavelengths shorter than 440 nm. PMID- 26378594 TI - [The Bioethics Challenges in Neonatology]. PMID- 26378595 TI - [The Best Interest of the Child in Neonatology: Is It Best for the Child?]. AB - Since its inceptions, the standard of best interest of the child was linked to decisions about suspend life-sustaining treatments in neonatal units and evaluation of treatments applied to children in terms of their quality of life. This origin has conditioned the interpretation of the standard from two extremes: a vitalistic one, and a non vitalistic interpretation that triumphed in Western bioethics and has led to the consecration of the standard of best interest of the child in the Convention on the Rights of the Child of United Nations. A detailed analysis reveals a simplistic, utilitarian and proportionalist standard, which change the basis of parenthood. We therefore believe that the standard of the best interest of the child is not the best for the child in neonatal intensive care units and especially not in the process of withhold or withdrawal life sustaining treatments. PMID- 26378592 TI - The Impact of Non-Enzymatic Reactions and Enzyme Promiscuity on Cellular Metabolism during (Oxidative) Stress Conditions. AB - Cellular metabolism assembles in a structurally highly conserved, but functionally dynamic system, known as the metabolic network. This network involves highly active, enzyme-catalyzed metabolic pathways that provide the building blocks for cell growth. In parallel, however, chemical reactivity of metabolites and unspecific enzyme function give rise to a number of side products that are not part of canonical metabolic pathways. It is increasingly acknowledged that these molecules are important for the evolution of metabolism, affect metabolic efficiency, and that they play a potential role in human disease age-related disorders and cancer in particular. In this review we discuss the impact of oxidative and other cellular stressors on the formation of metabolic side products, which originate as a consequence of: (i) chemical reactivity or modification of regular metabolites; (ii) through modifications in substrate specificity of damaged enzymes; and (iii) through altered metabolic flux that protects cells in stress conditions. In particular, oxidative and heat stress conditions are causative of metabolite and enzymatic damage and thus promote the non-canonical metabolic activity of the cells through an increased repertoire of side products. On the basis of selected examples, we discuss the consequences of non-canonical metabolic reactivity on evolution, function and repair of the metabolic network. PMID- 26378596 TI - [Analysis of the Debate on Neonatal Euthanasia Using Present Bioethical Literature]. AB - Nowadays, most of the deaths in neonatal ages take place in neonatal intensive care units and a significative number of these are involved in decisions of withholding or withdrawing medical care. The growing complexity of the health care in neonatal settings entails that end-of-life decision-making occurs more frequently. Personal views and attitudes on the best care of the severely ill newborns can be different, since to define objectively the "best interests" for the infant is not easy at all. The question of how to best care for such infants is ongoing, and there remain deep divisions within the field. The aim of this issue is to review the different criteria used in the western world, Europe, especially in the Netherlands, and the EEUU and the current debate on neonatal euthanasia. Poor vital prognosis, current and future quality of life and, after the Groningen protocol, unbearable suffering are the criteria commonly used in neonatal end-of-life decisions, including euthanasia. It is necessary to distinguish the decisions, in which euthanasia is chosen, of which they are an appropriate limit of therapeutic effort. PMID- 26378597 TI - [Nutrition and Hydration in Newborns: Limiting Treatment Decisions]. AB - Artificial hydration and nutrition are key elements in the treatment in Neonatal Units, especially in premature babies. It has led to improved survival and better clinical outcomes. Artificial nutrition is considered a medical treatment and, in such a way, a balance between burdens and benefits should be taken into consideration. Nevertheless decisions on withholding or withdrawing artificial nutrition and hydration have special and emotional considerations. In premature babies it is also necessary to consider than below the 34th week of gestational age, effective suckling is not present, and so, oral nutrition is not a possibility. Decisions regarding the end-of-life care of neonates should be made taking into account clinical facts but also values and beliefs of all concerned, and always "in the best interest" of infants. In order to consider all this aspects, we could respect withdrawing or withholding artificial nutrition and hydration in those babies with an ominous prognosis in a short term basis. It has not the same consideration if there is a clear life risk but a prognosis based on severe future burden, mainly because of neurologic damage. In those cases withholding or withdrawing fluids and feedings would be the direct cause of death. PMID- 26378598 TI - [Hans Jonas: Nature Conservation, Conservation of Life]. AB - This article discusses three of the problems that the German philosopher Hans Jonas studied. The first one addresses the need for a specific ethic dedicated to the moral dimension of environmental problems, from a different perspective to the traditional. The second problem is crucial in the discussion on environmental ethics: the value of the nature. Does the nature have an intrinsic value or an instrumental value only (to satisfy the interests of the human being)? The thesis of Jonas, which claimed that nature is a good in itself, were further elaborated here. And the third problem is the derivation of moral norms and the role of man in this ethic that recognizes a good in itself in nature. According to Jonas, the human being is not diminished by recognizing the intrinsic value of nature, since the man's uniqueness and value are unquestionable. From these three central issues, the paper highlights the importance of seeking the links between bioethics and environmental ethics to address the current environmental, social and economic crisis. PMID- 26378599 TI - [Research Biomedical Ethics and Practical Wisdom]. AB - As is well known, in the field of Biomedical Ethics some methodological proposals have been put forward. They try to provide some guidelines in order to take proper decisions. These methodologies are quite useful insofar as they supply reasons for action, but they are essentially insufficient. In fact, taking a good decision requires a special skill that goes beyond sheer technique, and this skill is traditionally called practical wisdom. Not in the usual and more outlying sense of sheer caution, but in the more central one of phronesis or prudentia. Although it is not a new notion, it usually appears blurred in biomedical decision-making theory, playing the wrong role, or in a marginal or indefinite way. From this postulate, we will try to make a double analysis. First, we will try to show the need for a proper understanding of the core role that phronesis plays in decision making. Second, we will try to get the original meaning of Aristotelian phronesis back. For reasons of space, in this paper the second question will be just partially addressed. PMID- 26378600 TI - [The Cinematographic Narration of the Posthumanism]. AB - The cinema constitutes today the aesthetic forefront of the posthumanism and a powerful instance of reflection on the posthuman future. In its more futurist dimension, the films present an evolutionary irreversible process linked to the technological development, which will determine the end of the human kind and its birth to a new posthuman reality. But it turns out paradoxical that the process of dehumanization of the human beings appears like inevitable and, nevertheless, appears as ideally Utopian the desire of humanization of the androids (to support the human values beyond the human kind). In consequence, the cinematographic reflection on posthumanism seems to be headed not towards the appearance of a new nature but towards the recovery of the genuine human values. PMID- 26378601 TI - [Project for the Creation of a Medical or Hospital Ethical Committee at a Local Level in the San Miguel Arcangel Hospital, District of San Miguelito, Province of Panama. Year 2013]. AB - The next project was based on the design on the creation of a medical ethical Committee at a hospital. It was developed at the San Miguel Arcangel Hospital, District of San Miguelito, Province of Panama, in 2013. Insomuch as the creation of social projects requires unified international parameters, format is taken from the Unesco's guides for the establishing and working of bioethics committees; adapted to the socio-economic, political and cultural context of the San Miguelito District, Panama Province. Furthermore to adapting to socio ecological aspect where the research project is carried out, the theoretical aspect includes from the ontological personalistic bioethics, where the cornerstone is the dignity of the human person. A study of perceptions of medical staff and nursing was developed on the management of the most common ethical dilemmas in the Hospital San Miguel Arcangel. The instrument used was a previously validated perception survey through a pilot test. Reliability was measured using Cronbach's alpha coefficient, and validity was obtained from the content. Satisfactory statistical results, that verify the working hypotheses on the recognition of the importance of autonomy, confidentiality, protection of vulnerable population, occupational health staff welfare and integration of bioethics at the institutional agenda, were obtained. However, there were particular aspects that indicate some doubt as to the management of some realities that are presented in the context of health care. PMID- 26378602 TI - [Teaching Bioethics to Students of Medicine with Problem-Based Learning (PBL)]. AB - We present the experience of the introduction of the subject of bioethics in a medical school in order to give to the 73 students of 5th degree skills to handle ethical conflicts in their practice. The main teaching method used was problem based learning (PBL). Skills objectives are described. The course was structured with a theoretical seminar (2 hours of duration), a workshop (2 hours of duration), 4 cases of PBL (24 hours of duration in total) and a role playing workshop (2 hours of duration). The seminar was aimed at the acquisition of theoretical knowledge. The PBL cases provided critical appraisal, obtaining knowledge, and application. The Role Playing set out for the practical demonstration of skills acquired in a simulated environment. A continuous assessment of students was performed throughout their practice on the PBL cases (40% of the final score) and also a final evaluation of the course was carried out via exam (60% of the final score). Students completed a course and faculty evaluation anonymously, which came out with positive results (median score of 8.5/10). PMID- 26378603 TI - [The Incidence of Biomedical Advances in Women. Some Reflections on the Spanish Legislation]. AB - This article will examine how and to what extent advances in biomedical sciences have played a role in transforming the status of women. It will highlight the positive aspects of these transformations but it will also examine the issues which are currently debated and which, in my opinion, require calm and considered reflection. PMID- 26378604 TI - [Medical Ethics Alive!, And More Alive The Bioethics!!]. PMID- 26378605 TI - [To Provoke Reflection]. PMID- 26378606 TI - Controlled Architecture of Dual-Functional Block Copolymer Brushes on Thin-Film Composite Membranes for Integrated "Defending" and "Attacking" Strategies against Biofouling. AB - We report a new macromolecular architecture of dual functional block copolymer brushes on commercial thin-film composite (TFC) membranes for integrated "defending" and "attacking" strategies against biofouling. Mussel-inspired catechol chemistry is used for a convenient immobilization of initiator molecules to the membrane surface with the aid of polydopamine (PDA). Zwitterionic polymer brushes with strong hydration capacity and quaternary ammonium salt (QAS) polymer brushes with bactericidal ability are sequentially grafted on TFC membranes via activators regenerated by electron transfer-atom transfer radical polymerization (ARGET-ATRP), an environmentally benign and controlled polymerization method. Measurement of membrane intrinsic transport properties in reverse osmosis experiments shows that the modified TFC membrane maintains the same water permeability and salt selectivity as the pristine TFC membrane. Chemical force microscopy and protein/bacterial adhesion studies are carried out for a comprehensive evaluation of the biofouling resistance and antimicrobial ability, demonstrating low biofouling propensity and excellent bacterial inactivation for the modified TFC membrane. We conclude that this polymer architecture, with complementary "defending" and "attacking" capabilities, can effectively prevent the attachment of biofoulants and formation of biofilms and thereby significantly mitigate biofouling on TFC membranes. PMID- 26378607 TI - Molecular epidemiology and surveillance of circulating rotavirus and adenovirus in Congolese children with gastroenteritis. AB - Infectious Diarrhea caused by rotavirus and adenovirus, is a leading cause of death in children in sub-Sahara Africa but there is limited published data on the diverse rotavirus genotypes and adenovirus serotypes circulating in the Republic of Congo. In this study, we investigated the prevalence of severe diarrhea caused by rotavirus A (RVA) and Adenovirus serotype 40 and 41 in Congolese children hospitalized with severe gastroenteritis. Stool samples were collected from 655 Congolese children less than 60 months of age hospitalized with acute gastroenteritis between June 2012 and June 2013. Rotavirus and adenovirus antigens were tested using commercially available ELISA kits and the RVA G- and P genotypes were identified by seminested multiplex RT-PCR. Three hundred and four (46.4%) children were tested positive for RVA. Adenovirus infection was found in 5.5% of the 564 tested children. Rotavirus infection was frequently observed in children between 6-12 months (55.9%). The dry season months recorded increased RVA infection while no seasonality of adenovirus infection was demonstrated. The most common RVA genotypes were G1 (57.5%), G2 (6.4%), G1G2 mixture (15.5%), P[8] (58%), P[6] (13.2%), and P[8]P[6] mixture (26%). Additionally, the genotype G12P[6] was significantly associated with increased vomiting. This first study on Congolese children demonstrates a high prevalence and clinical significance of existing rotavirus genotypes. Adenovirus prevalence is similar to that of other Central African countries. This baseline epidemiology and molecular characterization study will contribute significantly to the RVA surveillance after vaccine implementation in the country. PMID- 26378608 TI - Permeability test and slope stability analysis of municipal solid waste in Jiangcungou Landfill, Shaanxi, China. AB - With the rapid increase of city waste, landfills have become a major method to deals with municipal solid waste. Thus, the safety of landfills has become a valuable research topic. In this paper, Jiangcungou Landfill, located in Shaanxi, China, was investigated and its slope stability was analyzed. Laboratory tests were used to obtain permeability coefficients of municipal solid waste. Based on the results, the distribution of leachate and stability in the landfill was computed and analyzed. These results showed: the range of permeability coefficient was from 1.0 * 10(-7) cm sec(-1) to 6.0 * 10(-3) cm sec(-1) on basis of laboratory test and some parameters of similar landfills. Owing to the existence of intermediate cover layers in the landfill, the perched water level appeared in the landfill with heavy rain. Moreover, the waste was filled with leachate in the top layer, and the range of leachate level was from 2 m to 5 m in depth under the waste surface in other layers. The closer it gets to the surface of landfill, the higher the perched water level of leachate. It is indicated that the minimum safety factors were 1.516 and 0.958 for winter and summer, respectively. Additionally, the slope failure may occur in summer. IMPLICATIONS: The research of seepage and stability in landfills may provide a less costly way to reduce accidents. Landslides often occur in the Jiangcungou Landfill because of the high leachate level. Some measures should be implemented to reduce the leachate level. This paper investigated seepage and slope stability of landfills by numerical methods. These results may provide the basis for increasing stability of landfills. PMID- 26378609 TI - Neural immune modulation and immunotherapy assisted by focused ultrasound induced blood-brain barrier opening. AB - The central nervous system (CNS) has long been regarded as an immune-privileged site, with the blood-brain barrier (BBB) limiting the entering of systemic immune cells and components. Exposure of low-energy focused ultrasound (FUS) with the presence of microbubbles has been found to provide a temporary and targeted opening of the BBB without inflicting brain damage or inflammation, and is thus an attractive means of delivering CNS therapeutic agents and raising the potential for targeted CNS immunotherapy. Based on our recent studies on enhancing brain-tumor immune-related therapy via this mechanism, (1) we summarize current approaches using FUS-induced BBB opening to promote immune regulation and project potential directions for FUS-induced CNS immunotherapy. PMID- 26378610 TI - Impact of drying and thiel embalming on mechanical properties of achilles tendons. AB - Biomechanical research and orthopedic training is regularly carried out on human cadavers. Given the post-mortem decay, these cadavers were usually frozen or embalmed. The embalming method according to Dr. Thiel was often praised for the preservation of natural texture. The main aim of this article was to quantitatively analyze the impact of this embalming technique on the biomechanical properties. To that extent, Achilles tendons (calcaneal tendons) of seven cadavers have been tested. For each cadaver, a first tendon was tested following a fresh-frozen conservation, the other following the Thiel embalming process. The results indicated a significant difference in Young's modulus between both groups (P values = 0.046). The secondary aim of this article was to analyze the impact of exposure to room conditions and associated dehydration on the biomechanical properties of cadaver tissue. Therefore, each tendon was tested before and after 2 hr of exposure to room conditions. The resulting dehydration caused a significant increase of the Young's modulus for the thawed fresh-frozen tendons. The properties of the Thiel embalmed tendons were not significantly altered. In conclusion, this research promoted the use of fresh-frozen specimens for biomechanical testing. Effort should, however, be made to minimize dehydration of the tested specimens. PMID- 26378611 TI - Stroke, Major Bleeding, and Mortality Outcomes in Warfarin Users With Atrial Fibrillation and Chronic Kidney Disease: A Meta-Analysis of Observational Studies. AB - BACKGROUND: The use of warfarin in patients with atrial fibrillation (AF) and chronic kidney disease (CKD) can be problematic because of increased bleeding risk. We performed a systematic review and meta-analysis of observational studies that evaluated the use of warfarin in patients with AF and CKD to evaluate the risks of ischemic stroke/thromboembolism, major bleeding, and mortality. METHODS: PUBMED, EMBASE, CINAHL, ProQuest, and Google Scholar databases were electronically searched through January 12, 2015. Additionally, a manual search was performed for relevant references. Random-effects model was used to estimate the pooled hazard ratio (HR) with 95% CI. CKD was divided into non-end-stage CKD and end-stage CKD (on renal replacement therapy) and separate analyses were performed. RESULTS: Thirteen publications from 11 cohorts (six retrospective and five prospective) including >48,500 total patients with >11,600 warfarin users were included in the meta-analysis. In patients with AF and non-end-stage CKD, warfarin resulted in a lower risk of ischemic stroke/thromboembolism (HR, 0.70; 95% CI, 0.54-0.89; P = .004) and mortality (HR, 0.65; 95% CI, 0.59-0.72; P < .00001), but had no effect on major bleeding (HR, 1.15; 95% CI, 0.88-1.49; P = .31). In patients with AF and end-stage CKD, warfarin had no effect on the risks of stroke (HR, 1.12; 95% CI, 0.69-1.82; P = .65) and mortality (HR, 0.96; 95% CI, 0.81-1.13; P = .60), but increased the risks of major bleeding (HR, 1.30; 95% CI, 1.08-1.56; P = .005). CONCLUSIONS: Based on this meta-analysis, the use of warfarin for AF may have an unfavorable risk/benefit ratio in patients with end stage CKD but not in those with non-end-stage CKD. PMID- 26378612 TI - The Endoscopic Endonasal Approach to the Hypoglossal Canal: The Role of the Eustachian Tube as a Landmark for Dissection. AB - IMPORTANCE: Improvements in endoscopic technology and reconstructive techniques have made the endoscopic endonasal approach (EEA) a viable option to approach ventromedial lesions in the region of the hypoglossal canal. Prior to contemplating this surgical corridor, a thorough understanding of anatomic relationships and landmarks is essential to safely approach this region of the posterior skull base through an EEA. OBJECTIVE: To describe the surgical technique and anatomic landmarks in the EEA to the hypoglossal canal through referencing nasopharyngeal and posterior skull base anatomy. DESIGN, SETTING, AND PARTICIPANTS: Study of latex-injected cadaveric heads at the North Carolina Eye Bank Multidisciplinary Surgical Skills Laboratory at the University of North Carolina. INTERVENTIONS: An EEA to the hypoglossal canal was carried out bilaterally in 5 embalmed, latex-injected cadaver heads. MAIN OUTCOMES AND MEASURES: Cadaveric measurements of anatomic landmarks and relationships in the approach were obtained using a 10-cm surgical ruler and were reported as mean distances. Additionally, high-quality endoscopic images demonstrating the operative technique and anatomic relationships were obtained. RESULTS: The distance between the lacerum segment of the internal carotid arteries, the superolateral boundary, was 23.6 mm (SD, 11.8 mm). The distance between the anterolateral edge of the occipital condyles, the inferolateral boundary, was 19 mm (SD, 0.80 mm). The supracondylar groove was identified in the same anteroposterior plane as the nasopharyngeal orifice of the eustachian tube, and the anterior-most edge of the occipital condyle was 14 mm (SD, 0.82 mm) from the posterosuperior edge of the salpingopharyngeal fold. Additionally, the transtubercular corridor was on the same plane as the superior edge of the torus tubarius in the anteroposterior axis. The distance to the hypoglossal canal from midline was 10 mm, which was found after completing drilling in the transcondylar and transtubercular corridors. Last, the hypoglossal nerve rootlets were identified entering the canal 6 mm inferiorly and 8 mm laterally from the vertebrobasilar junction. CONCLUSIONS AND RELEVANCE: The eustachian tube and other elements of nasopharyngeal anatomy are fixed landmarks that provide important points of reference when approaching the hypoglossal canal through an EEA. A thorough understanding of these anatomic relationships is vital in safely navigating this direct, surgical corridor to the posterior fossa. PMID- 26378613 TI - "What Are You Thinking When You Look at Me?" A Pilot Study of the Use of Virtual Reality in Body Image. AB - Body image disturbance (BID) is implicated in the etiology, maintenance, and relapse of the eating disorders, and remains challenging to treat. New paradigms such as virtual reality (VR) may offer an ecologically viable method to assess and treat BID. This pilot study aimed to determine if a VR environment could elicit increased BID in a nonclinical group of women who were dieting due to body image concerns or nonclinical women who were not dieting. Forty-one nonclinical females participated in the VR paradigm (a London Bus Journey), completing pre and post measures of body image satisfaction, and social evaluative concerns. Results did not support the hypothesis that the virtual London Bus would elicit increased BID. However, dieters reported significantly higher levels of social evaluative concerns and comparison to avatars during the virtual environment compared with nondieters. Participants reported acceptable levels of sense of presence and enjoyment of the VR environment. Possible explanations for the failure of the VR environment to trigger increased BID are discussed, including choice of environment and avatar fidelity. In conclusion, this pilot study suggests that VR might have potential in the treatment of disturbed body image, while highlighting the need for further research into the required levels of representational and behavioral fidelity of virtual environments and avatars. PMID- 26378615 TI - Efficiency of Cordless Versus Cord Techniques of Gingival Retraction: A Systematic Review. AB - PURPOSE: Primarily to assess the efficacy of cordless versus cord techniques in achieving hemostasis control and gingival displacement and their influence on gingival/periodontal health. In addition, subjective factors reported by the patient (pain, sensitivity, unpleasant taste, discomfort) and operator's experience to both techniques were analyzed. MATERIALS AND METHODS: An electronic database search was conducted using five main databases ranging from publication year 1998 to December 2014 to identify any in vivo studies comparing cord and cordless gingival retraction techniques. RESULTS: Seven potential studies were analyzed. Out of the four articles that reported achievement of hemostasis control, three compared patients treated by an epi-gingival finish line and concluded that paste techniques were more efficient in controlling bleeding. Five studies reported on the amount of sulcus dilatation, with contrasting evidence. Only one study reported an increased gingival displacement when paste systems were used. Two studies did not observe any significant difference, although two showed greater gingival displacement associated with cords, particularly in cases where the finish line was placed at a subgingival level. Of the four studies that assessed the influence of both techniques on the gingival/periodontal health, three noted less traumatic injury to soft tissues when gingival paste was used. A paste system, in general, was documented to be more comfortable to patients and user-friendly to the operator. CONCLUSIONS: Because of heterogeneity of measurement variables across studies, this study precluded a meta-analytic approach. Although both techniques (cord/cordless) are reliable in achieving gingival retraction, some situations were identified wherein each of the techniques proved to be more efficient. PMID- 26378614 TI - GBA deficiency promotes SNCA/alpha-synuclein accumulation through autophagic inhibition by inactivated PPP2A. AB - Loss-of-function mutations in the gene encoding GBA (glucocerebrosidase, beta, acid), the enzyme deficient in the lysosomal storage disorder Gaucher disease, elevate the risk of Parkinson disease (PD), which is characterized by the misprocessing of SNCA/alpha-synuclein. However, the mechanistic link between GBA deficiency and SNCA accumulation remains poorly understood. In this study, we found that loss of GBA function resulted in increased levels of SNCA via inhibition of the autophagic pathway in SK-N-SH neuroblastoma cells, primary rat cortical neurons, or the rat striatum. Furthermore, expression of the autophagy pathway component BECN1 was downregulated as a result of the GBA knockdown induced decrease in glucocerebrosidase activity. Most importantly, inhibition of autophagy by loss of GBA function was associated with PPP2A (protein phosphatase 2A) inactivation via Tyr307 phosphorylation. C2-ceramide (C2), a PPP2A agonist, activated autophagy in GBA-silenced cells, while GBA knockdown-induced SNCA accumulation was reversed by C2 or rapamycin (an autophagy inducer), suggesting that PPP2A plays an important role in the GBA knockdown-mediated inhibition of autophagy. These findings demonstrate that loss of GBA function may contribute to SNCA accumulation through inhibition of autophagy via PPP2A inactivation, thereby providing a mechanistic basis for the increased PD risk associated with GBA deficiency. PMID- 26378616 TI - The Arts, Crafts, and Sciences of Psychotherapy. AB - Contemporary training and practice of psychotherapy and the research that supports it is the subject of this review. I discuss it in the light of what I value most from my own professional training, which was, in my opinion, highly privileged by comparison with what is offered today. A minimal hoped-for outcome is that younger readers will find valuable tidbits here and there that will be useful in their own versions of psychotherapy. A maximal hope is that a few individuals who choose to maintain clinical skills as well as emphasize psychotherapy research might be encouraged to follow their instincts toward excellence. They would allow their curiosity to bloom and their work to be creative and more adherent to the rules of natural science than time allows in these days of dashboards that count funding associated with numbers of publications, grants, teaching, and service hours. Admittedly, that path less well traveled would be risky, because what truly is new takes time to develop and implement and the outcomes when research truly can disconfirm hypotheses (as distinct from fail to confirm them) are, well, uncertain. PMID- 26378617 TI - Luminescence in phosphine-stabilized copper chalcogenide cluster molecules--a comparative study. AB - The electronic properties of a series of eight copper chalcogenide clusters including [Cu12S6(dpppt)4] (dpppt = Ph2P(CH2)5PPh2), [Cu12Se6(dppo)4] (dppo = Ph2P(CH2)8PPh2), [Cu12S6(dppf)4] (dppf = Ph2PCpFeCpPPh2), [Cu12S6(PPh2Et)8], [Cu12S6(PEt3)8], [Cu24S12(PEt2Ph)12], [Cu20S10(PPh3)8], and [Cu20S10(P(t)Bu3)8] were investigated by absorption and photoluminescence (PL) spectroscopy as well as time-dependent density functional theory calculations. Major features of the experimental electronic absorption spectra are generally well-reproduced by the spectra simulated from the calculated singlet transitions. Visualization of the nonrelaxed difference densities indicates that for all compounds transitions at higher energies (above ~2.5 eV, i.e., below ~495 nm) predominantly involve excitations of electrons from orbitals of the cluster core to ligand orbitals. Conversely, the natures of the lower-energy transitions are found to be highly sensitive to the specifics of the ligand surface. Bright red PL (centered at ~650 700 nm) in the solid state at ambient temperature is found for complexes with all 'Cu12S6' (E = S, Se) cores as well as the dimeric 'Cu24S12', although in [Cu12S6(dppf)4], the PL appears to be efficiently quenched by the ferrocenyl groups. Of the two isomeric 'Cu20S10' complexes the prolate cluster [Cu20S10(PPh3)8] shows a broad emission that is centered at ~820 nm, whereas the oblate cluster [Cu20S10(P(t)Bu3)8] displays a relatively weak orange emission at ~575 nm. The emission of all complexes decays on the time scale of a few microseconds at ambient temperature. A very high photostability is quantitatively estimated for the representative complex [Cu12S6(dpppt)4] under anaerobic conditions. PMID- 26378618 TI - Integrated glycoprotein immobilization method for glycopeptide and glycan analysis of cardiac hypertrophy. AB - Post-translational modifications of proteins can have a major role in disease initiation and progression. Incredible efforts have recently been made to study the regulation of glycoproteins for disease prognosis and diagnosis. It is essential to elucidate glycans and intact glycoproteins to understand the role of glycosylation in diseases. Sialylated N-glycans play crucial roles in physiological and pathological processes; however, it is laborious to study sialylated glycoproteins due to the labile nature of sialic acid residues. In this study, an integrated platform is developed for the analysis of intact glycoproteins and glycans using a chemoenzymatic approach for immobilization and derivatization of sialic acids. N-Glycans, deglycosylated proteins, and intact glycoproteins from heart tissues of wild type (WT) and transverse aortic constriction (TAC) mouse models were analyzed. We identified 291 unique glycopeptides from 195 glycoproteins; the comparative studies between WT and TAC mice indicate the overexpression of extracellular proteins for heart matrix remodeling and the down-regulation of proteins associated with energy metabolism in cardiac hypertrophy. The integrated platform is a powerful tool for the analysis of glycans and glycoproteins in the discovery of potential cardiac hypertrophy biomarkers. PMID- 26378619 TI - Stealth effect of biomolecular corona on nanoparticle uptake by immune cells. AB - When injected in a biological milieu, a nanomaterial rapidly adsorbs biomolecules forming a biomolecular corona. The biomolecular corona changes the interfacial composition of a nanomaterial giving it a biological identity that determines the physiological response. Characterization of the biomolecular structure and composition has received increasing attention mostly due to its detrimental impact on the nanomaterial's metabolism in vivo. It is generally accepted that an opsonin-enriched biomolecular corona promotes immune system recognition and rapid clearance from circulation. Here we applied dynamic light scattering and nanoliquid chromatography tandem mass spectrometry to thoroughly characterize the biomolecular corona formed around lipid and silica nanoparticles (NPs). Incubation with human plasma resulted in the formation of NP-biomolecular coronas enriched with immunoglobulins, complement factors, and coagulation proteins that bind to surface receptors on immune cells and elicit phagocytosis. Conversely, we found that protein-coated NPs were protected from uptake by macrophage RAW 264.7 cells. This implies that the biomolecular corona formation provides a stealth effect on macrophage recognition. Our results suggest that correct prediction of the NP's fate in vivo will require more than just the knowledge of the biomolecular corona composition. Validation of efficient methods for mapping protein binding sites on the biomolecular corona of NPs is an urgent task for future research. PMID- 26378620 TI - Mechanism-Based Post-Translational Modification and Inactivation in Terpene Synthases. AB - Terpenes are ubiquitous natural chemicals with diverse biological functions spanning all three domains of life. In specialized metabolism, the active sites of terpene synthases (TPSs) evolve in shape and reactivity to direct the biosynthesis of a myriad of chemotypes for organismal fitness. As most terpene biosynthesis mechanistically involves highly reactive carbocationic intermediates, the protein surfaces catalyzing these cascade reactions possess reactive regions possibly prone to premature carbocation capture and potentially enzyme inactivation. Here, we show using proteomic and X-ray crystallographic analyses that cationic intermediates undergo capture by conserved active site residues leading to inhibitory self-alkylation. Moreover, the level of cation mediated inactivation increases with mutation of the active site, upon changes in the size and structure of isoprenoid diphosphate substrates, and alongside increases in reaction temperatures. TPSs that individually synthesize multiple products are less prone to self-alkylation then TPSs possessing relatively high product specificity. In total, the results presented suggest that mechanism-based alkylation represents an overlooked mechanistic pressure during the evolution of cation-derived terpene biosynthesis. PMID- 26378621 TI - Tris(2-chloroethyl)phosphate-induced cell growth arrest via attenuation of SIRT1 independent PI3K/Akt/mTOR pathway. AB - Tris(2-chloroethyl)phosphate (TCEP) as an organophosphorus flame retardant and plasticizer has been widely used in industrial and household products. It not only was detected in residential indoor air and dust, surface and drinking water, but also in human plasma and breast milk, and tissue samples of liver, kidneys and brain from rodents. TCEP is classified as carcinogenic category 2 and toxic for reproduction category 1B. Sufficient evidence from experimental animals indicated carcinogenicity of TCEP in the liver, and kidneys as well as cell loss in the brain. However, the underlying mechanisms of TCEP-induced hepatotoxicity are mostly unknown. We investigated the in vitro effects of TCEP as well as TCEP induced cell growth in the L02 and HepG2 cells through the PI3K/Akt/mTOR pathway. We found that TCEP reduced cell viability of these cell lines, induced the cell growth arrest, upregulated mRNA and protein levels of SIRT1, and attenuated the PI3K/Akt/mTOR pathway. However, growth arrest of the L02 and HepG2 cells were aggravated after inhibiting the SIRT1 expression with EX-527. The findings above suggested that TCEP induced the cell growth arrest of L02 and HepG2 cells via attenuation of the SIRT1-independent PI3K/Akt/mTOR pathway. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26378622 TI - Wet Chemistry Synthesis of Multidimensional Nanocarbon-Sulfur Hybrid Materials with Ultrahigh Sulfur Loading for Lithium-Sulfur Batteries. AB - An optimized nanocarbon-sulfur cathode material with ultrahigh sulfur loading of up to 90 wt % is realized in the form of sulfur nanolayer-coated three dimensional (3D) conducting network. This 3D nanocarbon-sulfur network combines three different nanocarbons, as follows: zero-dimensional carbon nanoparticle, one-dimensional carbon nanotube, and two-dimensional graphene. This 3D nanocarbon sulfur network is synthesized by using a method based on soluble chemistry of elemental sulfur and three types of nanocarbons in well-chosen solvents. The resultant sulfur-carbon material shows a high specific capacity of 1115 mA h g( 1) at 0.02C and good rate performance of 551 mA h g(-1) at 1C based on the mass of sulfur-carbon composite. Good battery performance can be attributed to the homogeneous compositing of sulfur with the 3D hierarchical hybrid nanocarbon networks at nanometer scale, which provides efficient multidimensional transport pathways for electrons and ions. Wet chemical method developed here provides an easy and cost-effective way to prepare sulfur-carbon cathode materials with high sulfur loading for application in high-energy Li-S batteries. PMID- 26378624 TI - Synthesis and Characterization of Poly(glyceric Acid Carbonate): A Degradable Analogue of Poly(acrylic Acid). AB - The synthesis and characterization of a degradable version of poly(acrylic acid), poly(glyceric acid carbonate), are reported. Specifically, atactic and isotactic poly(benzyl glycidate carbonate)s are obtained via the ring-opening copolymerization of rac-/(R)-benzyl glycidate with CO2 using a bifunctional rac /(S,S)-cobalt salen catalyst in high carbonate linkage selectivity (>99%) and polymer/cyclic carbonate selectivity (~90%). Atactic poly(benzyl glycidate carbonate) is an amorphous material with a T(g) (glass transition temperature) of 44 degrees C, while its isotactic counterpart synthesized from enantiopure epoxide and catalyst is semicrystalline with a T(m) (melting temperature) = 87 degrees C. Hydrogenolysis of the resultant polymers affords the poly(glyceric acid carbonate). Poly(glyceric acid carbonate) exhibits an improved cell cytotoxicity profile compared to poly(acrylic acid). Poly(glyceric acid carbonate)s also degrade remarkably fast (t(1/2) ~ 2 weeks) compared to poly(acrylic acid). Cross-linked hydrogels prepared from poly(glyceric acid carbonate) and poly(ethylene glycol) diaziridine show significant degradation in pH 8.4 aqueous buffer solution compared to similarly prepared hydrogels from poly(acrylic acid) and poly(ethylene glycol) diaziridine. PMID- 26378623 TI - Toluidine Blue 0.05% Vital Staining for the Diagnosis of Ocular Surface Squamous Neoplasia in Kenya. AB - IMPORTANCE: Clinical features are unreliable for distinguishing ocular surface squamous neoplasia (OSSN) from benign conjunctival lesions. OBJECTIVE: To evaluate the adverse effects, accuracy, and interobserver variation of toluidine blue 0.05% vital staining in distinguishing OSSN, confirmed by histopathology, from other conjunctival lesions. DESIGN, SETTING, AND PARTICIPANTS: Cross sectional study in Kenya from July 2012 through July 2014 of 419 adults with suspicious conjunctival lesions. Pregnant and breastfeeding women were excluded. EXPOSURES: Comprehensive ophthalmic slitlamp examination was conducted. Vital staining with toluidine blue 0.05% aqueous solution was performed before surgery. Initial safety testing was conducted on large tumors scheduled for exenteration looking for corneal toxicity on histology before testing smaller tumors. We asked about pain or discomfort after staining and evaluated the cornea at the slitlamp for epithelial defects. Lesions were photographed before and after staining. MAIN OUTCOMES AND MEASURES: Diagnosis was confirmed by histopathology. Six examiners assessed photographs from a subset of 100 consecutive participants for staining and made a diagnosis of OSSN vs non-OSSN. Staining was compared with histopathology to estimate sensitivity, specificity, and predictive values. Adverse effects were enumerated. Interobserver agreement was estimated using the kappa statistic. RESULTS: A total of 143 of 419 participants (34%) had OSSN by histopathology. The median age of all participants was 37 years (interquartile range, 32-45 years) and 278 (66%) were female. A total of 322 of the 419 participants had positive staining while 2 of 419 were equivocal. There was no histological evidence of corneal toxicity. Mild discomfort was reported by 88 (21%) and mild superficial punctate keratopathy seen in 7 (1.7%). For detecting OSSN, toluidine blue had a sensitivity of 92% (95% CI, 87%-96%), specificity of 31% (95% CI, 25%-36%), positive predictive value of 41% (95% CI, 35%-46%), and negative predictive value of 88% (95% CI, 80%-94%). Interobserver agreement was substantial for staining (kappa = 0.76) and moderate for diagnosis (kappa = 0.40). CONCLUSIONS AND RELEVANCE: With the high sensitivity and low specificity for OSSN compared with histopathology among patients with conjunctival lesions, toluidine blue 0.05% vital staining is a good screening tool. However, it is not a good diagnostic tool owing to a high frequency of false-positives. The high negative predictive value suggests that a negative staining result indicates that OSSN is relatively unlikely. PMID- 26378625 TI - Severe Persistent Allergic Rhinitis. Inflammation but No Histologic Features of Structural Upper Airway Remodeling. AB - RATIONALE: Increases in airway smooth muscle, extracellular matrix, and vascularity are prominent features of airway remodeling in asthma, whereas the extent of such remodeling in patients with persistent allergic rhinitis (PAR) is unknown. OBJECTIVES: To test the hypothesis that upper airway remodeling is a feature of PAR. METHODS: Total nasal symptoms scores, nasal biopsies, and Th1 and Th2 cytokines from nasal lavage were assessed in subjects with severe PAR (n = 46) and healthy control subjects (n = 19). Angiolymphangiogenesis was examined using immunohistochemistry staining against CD31 (vascular endothelial cells), vascular endothelial growth factor-A, and D2-40 (lymphatic endothelial cells). Collagen and extracellular matrix proteins, such as heat shock protein-47 (markers of collagen synthesis), matrix metalloproteinase-9, and tissue inhibitor metalloproteinase-1, and alpha-smooth muscle actin (myofibroblasts) were evaluated as markers of activation of upper airway remodeling using image analysis, together with reticular basement membrane thickness, mucus gland area, collagen area, and submucosal effector inflammatory cells. MEASUREMENTS AND MAIN RESULTS: Total nasal symptoms scores, visual analog scale, and total quality of life were significantly higher in PAR compared with healthy control subjects (P < 0.0001). Nasal lavage cytokine levels of IL-4 (P < 0.01), IL-5, and IL-13 (P < 0.001, respectively) were significantly higher in PAR compared with healthy control subjects. In addition there was an increase in submucosal eosinophils (P = 0.06). No statistical difference in terms of angiogenesis, lymphangiogenesis, deposition of extracellular matrix, collagen markers, reticular basement membrane thickness, or glandular percentage area was observed between PAR and healthy control subjects. CONCLUSIONS: Our data suggest that tissue remodeling is not a feature of PAR and argues that in contrast to asthma, targeting remodeling in allergic rhinitis may not be appropriate as a therapeutic approach. PMID- 26378626 TI - Synthesis of 2-Aminoazoles from Thioesters via alpha-Heterosubstituted Ketones by Copper-Mediated Cross-Coupling. AB - Facile synthesis of a variety of alpha-heterosubstituted ketones under mild conditions was achieved by copper-mediated cross-coupling of thioesters with functionalized organostannanes. Application of this coupling methodology provided a concise pathway for the conversion of carboxylic acids to 2-aminoimidazoles, 2 aminothiazoles, and 2-aminooxazoles via thioesters in practical yields. PMID- 26378627 TI - Characterization and control of surfactant-mediated Norovirus interactions. AB - Understanding of the colloidal interactions of Norovirus particles in aqueous medium could provide insights on the origins of the notorious stability and infectivity of these widespread viral agents. We characterized the effects of solution pH and surfactant type and concentration on the aggregation, dispersion, and disassembly of Norovirus virus-like particles (VLPs) using dynamic light scattering, electrophoretic light scattering, and transmission electron microscopy. Owing to net negative surface charge of the VLPs at neutral pH, low concentrations of cationic surfactant tend to aggregate the VLPs, whereas low concentrations of anionic surfactant tend to disperse the particles. Increasing the concentration of these surfactants beyond their critical micelle concentration leads to virus capsid disassembly and breakdown of aggregates. Non ionic surfactants, however, had little effect on virus interactions and likely stabilized them additionally in suspension. The data were interpreted on the basis of simple models for surfactant binding and re-charging of the virus capsid. We used zeta potential data to characterize virus surface charge and interpret the mechanisms behind these demonstrated surfactant-virus interactions. The fundamental understanding and control of these interactions will aid in practical formulations for virus inactivation and removal from contaminated surfaces. PMID- 26378628 TI - Mice Deficient in CIZ/NMP4 Develop an Attenuated Form of K/BxN-Serum Induced Arthritis. AB - CIZ/NMP4 (Cas interacting zinc finger protein, Nmp4, Zfp384) is a transcription factor that is known to regulate matrix related-proteins. To explore the possible pathophysiological role of CIZ/NMP4 in arthritis, we examined CIZ/NMP4 expression in articular cartilage in arthritis model. CIZ/NMP4 was expressed in the articular chondrocytes of mice at low levels while its expression was enhanced when arthritis was induced. Arthritis induction increased clinical score in wild type mice. In contrast, CIZ/NMP4 deficiency suppressed such rise in the levels of arthritis score and swelling of soft tissue. CIZ/NMP4 deficiency also reduced invasion of inflammatory cells in joint tissue. Quantitative PCR analyses of mRNA from joints revealed that arthritis-induced increase in expressions of IL-1beta was suppressed by CIZ/NMP4 deficiency. CIZ/NMP4 bound to IL-1beta promoter and activated its transcription. The increase in CIZ/NMP4 in arthritis was also associated with enhancement in bone resorption and cartilage matrix degradation. In fact, RANKL, a signaling molecule prerequisite for osteoclastogenesis and, MMP 3, a clinical marker for arthritis were increased in joints upon arthritis induction. In contrast, CIZ/NMP4 deficiency suppressed the arthritis-induced increase in bone resorption, expression of RANKL and MMP-3 mRNA. Thus, CIZ/NMP4 plays a role in the development of arthritis at least in part through regulation of key molecules related to the arthritis. PMID- 26378629 TI - The Hidden Pathways in Dense Energy Materials - Oxygen at Defects in Nanocrystalline Metals. AB - Highly abundant oxygen-rich line defects (blue) can act as fast oxygen transport paths. These defects show similar chemistry and therefore similar catalytic activity to the materials surface. These results provide the opportunity to design and produce simple scalable structures as catalysts, whose functionality derives from internal defects rather than from the materials surfaces. PMID- 26378632 TI - Perception of stimuli by preterm infants. PMID- 26378630 TI - Essential phospholipids prevent islet damage induced by proinflammatory cytokines and hypoxic conditions. AB - BACKGROUND: The pancreatic islet damage that occurs through an inflammatory response and hypoxia after infusion is a major hurdle in islet transplantation. Because essential phospholipids (EPL) have been shown to exhibit anti inflammatory properties in liver disease, we analysed their protective effect on islets in inflammatory or hypoxic conditions. METHODS: We evaluated the viability of mouse and human islets cultured with cytokines or in hypoxic conditions for 48 h and measured cytokine expression in islets by quantitative polymerase chain reaction. We then employed an in vivo mouse assay, transplanting a marginal dose of human islets treated with or without EPL into the subcapsule of the kidney in diabetic nude mice and determining the cure rate. RESULTS: The viability of mouse and human islets damaged by cytokines was significantly improved by supplementation of EPL in the culture (p = 0.003 and <0.001 for mouse and human islets respectively). EPL significantly inhibited intracellular expression of IL 1beta and IL-6 in cytokine-damaged human islets (p < 0.001). The viability of human islets in hypoxic conditions was significantly better when treated with EPL (p < 0.001). In the in vivo mouse assay, the EPL-treated islet group had a higher cure rate than the untreated control, with marginal statistical significance (75 and 17% respectively, p = 0.07). CONCLUSIONS: EPL could be a potent agent to protect islets from inflammatory and hypoxic conditions after isolation procedures. Further studies to clarify the effect of EPL in islet transplantation are warranted. PMID- 26378633 TI - Neonatal weight loss and exclusive breastfeeding. PMID- 26378634 TI - Should babies be watching and using screens? The answer is surprisingly complicated. PMID- 26378635 TI - Reducing lifestyle risk in childhood cancer survivors. PMID- 26378636 TI - Bengt Hagberg. PMID- 26378638 TI - Foreword. Nonalcoholic Fatty Liver Disease. PMID- 26378637 TI - First-Line Aldoxorubicin vs Doxorubicin in Metastatic or Locally Advanced Unresectable Soft-Tissue Sarcoma: A Phase 2b Randomized Clinical Trial. AB - IMPORTANCE: Standard therapy for advanced soft-tissue sarcoma has not changed substantially in decades, and patient prognosis remains poor. Aldoxorubicin, a novel albumin-binding prodrug of doxorubicin, showed clinical activity against advanced soft-tissue sarcoma in phase 1 studies. OBJECTIVE: To evaluate efficacy and safety of aldoxorubicin vs doxorubicin in patients with advanced soft-tissue sarcoma. DESIGN, SETTING, AND PARTICIPANTS: International, multicenter, phase 2b, open-label, randomized study at general community practices, private practices, or institutional practices. Between August 2012 and December 2013, 140 patients with previously untreated locally advanced, unresectable, or metastatic soft tissue sarcoma were screened. INTERVENTIONS: Randomization (2:1) to aldoxorubicin 350 mg/m2 (dose equivalent to doxorubicin 260 mg/m2) or doxorubicin 75 mg/m2, administered once every 3 weeks for up to 6 cycles. MAIN OUTCOMES AND MEASURES: Primary end point was progression-free survival. Secondary end points were 6 month progression-free survival, overall survival, tumor response rate, and safety. All efficacy end points were evaluated by independent and local review. RESULTS: A total of 126 patients were randomized, and 123 received aldoxorubicin (n = 83) or doxorubicin (n = 40). Median (range) patient age was 54.0 (21-77 years); 42 (34%) had leiomyosarcoma. By independent review, median progression free survival was significantly improved (5.6 [95% CI, 3.0-8.1] vs 2.7 [95% CI, 1.6-4.3] months; P = .02) with aldoxorubicin compared with doxorubicin, as was the rate of 6-month progression-free survival (46% and 23%; P = .02). Median overall survival was 15.8 (95% CI, 13.0 to not available) months with aldoxorubicin and 14.3 (95% CI, 8.6-20.6) months with doxorubicin (P = .21). Overall tumor response rate (by Response Evaluation Criteria in Solid Tumors, version 1.1) by independent review was higher with aldoxorubicin than with doxorubicin (25% [20 patients, all partial response] vs 0%). Grade 3 or 4 neutropenia was more frequent with aldoxorubicin than with doxorubicin (24 [29%] vs 5 [12%]), but not grade 3 or 4 febrile neutropenia (12 [14%] vs 7 [18%]). No acute cardiotoxic effects were observed with either treatment, although left ventricular ejection fraction less than 50% occurred in 3 of 40 patients receiving doxorubicin. CONCLUSIONS AND RELEVANCE: Single-agent aldoxorubicin therapy showed superior efficacy over doxorubicin by prolonging progression-free survival and improving rates of 6-month progression-free survival and tumor response. Aldoxorubicin therapy exhibited manageable adverse effects, without unexpected events, and without evidence of acute cardiotoxicity. Further investigation of aldoxorubicin therapy in advanced soft-tissue sarcoma is warranted. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01514188. PMID- 26378639 TI - Diagnosis and Assessment of NAFLD: Definitions and Histopathological Classification. AB - Nonalcoholic fatty liver disease (NAFLD) comprises a spectrum of clinical and histopathological changes including "simple" steatosis, steatosis with inflammation, steatohepatitis, cirrhosis, and hepatocellular carcinoma. It was initially described in the context of drug-induced liver injury and acute liver disease following jejunoileal bypass surgery, but since the early 1980s it has been widely acknowledged as the hepatic manifestation of metabolic syndrome. It now represents a burgeoning public health crisis and is fast becoming the main indication for liver transplantation in some parts of the world. Its true incidence and prevalence are unknown, although estimates have been made from large imaging studies. Liver biopsy interpretation is still regarded as the gold standard for making accurate diagnoses in NAFLD, but sampling limitations are recognized. Furthermore, clear definitions for key histopathological components have been lacking, resulting in significant interobserver variations in making a diagnosis of steatohepatitis. In this review the authors consider some aspects of classification and variant forms of NAFLD such as that occurring in children. They provide an update on grading and staging systems and histopathological prognostic factors, and address the role of liver biopsy in contemporary clinical care of patients with NAFLD. PMID- 26378640 TI - Epidemiology and Natural History of Nonalcoholic Fatty Liver Disease. AB - The epidemic of obesity has resulted in a parallel incremental burden of nonalcoholic fatty liver disease (NAFLD) worldwide. Nonalcoholic fatty liver disease includes a spectrum of liver disease that ranges from simple fat accumulation in the liver to necroinflammation, fibrosis, cirrhosis, and hepatocellular carcinoma, which in essence represent the stages of the natural history of NAFLD. The rising prevalence of NAFLD globally may be accounted for by changes in dietary habits and an increase in sedentary lifestyle. Nonalcoholic steatohepatitis (NASH), the aggressive form of NAFLD, is currently the second leading etiology of liver disease among adults awaiting liver transplantation in the United States. In the current review, the authors discuss the uncertainty around the progression from NAFL (steatosis) to NASH (steatohepatitis), the undisputed progression of NASH to cirrhosis, and the risk factors that predispose to such progression. The published literature on the long-term cardiovascular complications and liver-related mortality of NAFLD is also discussed. PMID- 26378641 TI - Systemic Complications of Nonalcoholic Fatty Liver Disease: When the Liver Is Not an Innocent Bystander. AB - The top three leading causes of death in patients with nonalcoholic fatty liver disease (NAFLD) in descending order are cardiovascular disease, cancer, and liver disease. It is clear now that the increased risk of metabolic and macro- and microvascular complications in NAFLD stems from the associated features of metabolic syndrome. However, NAFLD itself may contribute to the spectrum of risk factors associated with insulin resistance. The primary focus of this review is to summarize the main systemic associations of NAFLD, as well as to discuss the mechanisms that link them to NAFLD. Hepatic lipid accumulation in NAFLD impairs hepatic glucose and lipid metabolism further increasing the risk of type 2 diabetes mellitus and of cardiovascular disease, independently of established risk factors. The incidence, prevalence, and severity of these complications are proportional to the histological severity of liver damage suggesting that NAFLD, but particularly nonalcoholic steatohepatitis, can also contribute to the low grade inflammatory state through the systemic release of several markers of inflammation, oxidative stress, and of procoagulant factors. The clinical implication of these findings is that patients with NAFLD require a multidisciplinary evaluation, with a major focus on type 2 diabetes mellitus and cardiovascular disease complications and may benefit from more intensive surveillance and early treatment interventions to decrease the risk for cardiovascular and kidney complications. PMID- 26378642 TI - Fatty Acid and Glucose Sensors in Hepatic Lipid Metabolism: Implications in NAFLD. AB - The term nonalcoholic fatty liver disease (NAFLD) covers a pathologic spectrum from lipid accumulation alone (simple steatosis) to steatosis with associated inflammation and fibrosis (nonalcoholic steatohepatitis [NASH]). Nonalcoholic steatohepatitis can progress to cirrhosis and potentially to hepatocellular carcinoma. Although a genetic predisposition has been highlighted, NAFLD is strongly associated with an unhealthy lifestyle and hypercaloric diet in the context of obesity and metabolic disease. The dysregulation of specific pathways (insulin signaling, mitochondrial function, fatty acid, and lipoprotein metabolism) have been linked to steatosis, but elucidating the molecular events determining evolution of the disease still requires further research before it can be translated into specific personalized interventional strategies. In this review, the authors focus on the early events of the pathophysiology of NASH, dissecting the metabolic and nutritional pathways involving fatty acids and glucose sensors that can modulate lipid accumulation in the liver, but also condition the progression to cirrhosis and hepatocellular carcinoma. PMID- 26378643 TI - The Gut Microbiota and Nonalcoholic Fatty Liver Disease. AB - With the recognition of the various metabolic functions of the gut microbiome and of its putative role in obesity, an investigation of the contribution of the bacterial populations of the gastrointestinal tract to the metabolic syndrome and its hepatic manifestation-nonalcoholic liver disease (NAFLD)-became inevitable. Furthermore, the central role of an altered microbiome in the precipitation of infectious and noninfectious complications of liver disease was described decades ago. The contribution of the microbiome to the pathogenesis of NAFLD has been extensively studied in animal models. Convincing evidence for a central role for an altered microbiome (through multiple mechanisms), coupled with such phenomena as impaired gut barrier function and an aberrant host immune response, has been amply demonstrated. The accumulation of a similar level of evidence from human studies has proven more challenging; however, incriminating data accumulate. Although animal studies have demonstrated the benefits of interventions that modulate the microbiome and of probiotics, in particular, in reducing steatosis and preventing progression to steatohepatitis, data in man are scanty and high quality clinical trials of probiotics and other strategies are needed. PMID- 26378644 TI - The Genetics of Nonalcoholic Fatty Liver Disease: Spotlight on PNPLA3 and TM6SF2. AB - Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum that spans simple steatosis, through nonalcoholic steatohepatitis (NASH) to fibrosis and ultimately cirrhosis. Nonalcoholic fatty liver disease is characterized by substantial interpatient variation in rate of progression and disease outcome: Although up to 25% of the general population are at risk of progressive disease, only a minority experience associated liver-related morbidity. Nonalcoholic fatty liver disease is considered a complex disease trait that occurs when environmental exposures act upon a susceptible polygenic background composed of multiple independent modifiers. Recent advances include the identification of PNPLA3 as a modifier of disease outcome across the full spectrum of NAFLD from steatosis to advanced fibrosis and hepatocellular carcinoma; and the discovery of TM6SF2 as a potential "master regulator" of metabolic syndrome outcome, determining not only risk of advanced liver disease, but also cardiovascular disease outcomes. In this article, the authors will review the field, discussing in detail the current status of research into these important genetic modifiers of NAFLD progression. PMID- 26378645 TI - Noninvasive Evaluation of Nonalcoholic Fatty Liver Disease. AB - Key issues in patients with nonalcoholic fatty liver disease (NAFLD) are the differentiation of nonalcoholic steatohepatitis (NASH) from simple steatosis and staging of liver fibrosis, as patients with NASH/advanced fibrosis are at greatest risk of developing complications of end-stage liver disease. The controlled attenuation parameter is the most promising noninvasive technique for detecting and quantifying hepatic steatosis, but needs to be implemented with the XL probe and compared with ultrasound that, despite its limitations, remains the most widely used method. Cytokeratin-18 is currently the most extensively validated serum marker of NASH as a stand-alone test or as part of prediction models. However, it is not widely available and thus has not been introduced yet into practice. Transient elastography, as well as FIB-4 and NAFLD fibrosis scores are the best methods to rule out severe fibrosis and cirrhosis. However, the high rate of unreliable results with transient elastography remains a challenge, which is not completely addressed by the use of the XL probe. Given the high prevalence of NAFLD in the general population, these noninvasive methods could be used in clinical practice as first-line tools to screen patients with NAFLD to help determine those who may still require a liver biopsy. PMID- 26378646 TI - Nonalcoholic Fatty Liver Disease-Related Hepatocellular Carcinoma: A Problem of Growing Magnitude. AB - Hepatocellular carcinoma (HCC) is a cancer with globally rising incidence. Growing evidence supports associations between metabolic syndrome and diabetes as well as obesity and HCC arising in patients with nonalcoholic fatty liver disease (NAFLD). This constitutes a problem of alarming magnitude given the rising epidemic of these conditions. The role of diabetes seems to be particularly important when associated with obesity or cirrhosis. Excess hepatic iron may be another potential risk factor for the development of NAFLD-associated HCC. In the context of NAFLD, HCC frequently develops in a not-yet cirrhotic liver. As there are no surveillance programs for these patients, diagnosis often occurs at a tumor stage beyond curative options. Clinical, tumor, and patient characteristics in NAFLD-associated HCC differ from other etiologies. Older age and cardiovascular comorbidities may limit treatment options further. The outcome in patients with NAFLD-associated early HCC is excellent and therefore aggressive treatment should be pursued in appropriate patients. Population-based prevention to reduce the culprit-NAFLD-early recognition through targeted surveillance programs in risk-stratified patients and effective treatment of HCC associated with NAFLD are urgently needed. In this review, the authors summarize the epidemiology, risk factors, features, and prevention of NAFLD-associated HCC. PMID- 26378647 TI - Nonalcoholic Fatty Liver Disease Management: Dietary and Lifestyle Modifications. AB - Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of abnormalities that can range from bland liver fat (steatosis), to hepatic inflammation and liver injury (steatohepatitis). It is estimated that NAFLD will become the principal cause of liver disease in Western nations and the leading indication for liver transplantation. Advancements in disease recognition and management are therefore paramount. Although the development of new, reliable drug therapies is vital, lifestyle interventions remain the most effective treatment modality. In addition to weight loss as a primary measure of treatment success, there is growing recognition that other endpoints, including the prevention or delay of diabetes onset, reduced cardiovascular events, prevention of cancer, and improved overall mortality, are equally important outcomes that can be independently modified by lifestyle change. Moreover, NAFLD is inextricably part of a complex, systemic disease process that is linked with deeply entrenched maladaptive lifestyle behaviors. Thus, a holistic, multidisciplinary, and individualized approach to disease management will be the key to achieving any realistic population-level change. PMID- 26378649 TI - The Evolving Role of Nonalcoholic Fatty Liver Disease in Hepatic Neoplasia: Inflammatory Hepatocellular Adenoma in a Man with Metabolic Syndrome. AB - Growing awareness of the spectrum of liver diseases related to nonalcoholic fatty liver disease (NAFLD) has drawn attention to the complex pathogenetic pathways that are operative in livers with macrovesicular steatosis and to the potential development of hepatocellular adenoma and hepatocellular carcinoma in unusual clinical settings. This report describes an older man with metabolic syndrome who developed a 3.9 cm. right lobe liver mass that on directed needle biopsy showed the features of an inflammatory hepatocellular adenoma, including immunostain positivity for serum amyloid A. The case highlights the many factors involved in the pathogenesis of liver tumors in the steatotic liver of NAFLD, particularly the interplay of inflammatory mediators, adiponectin and leptin, genomics and metabolomics, lipotoxicity, endotoxin, and hepatic stellate cells. PMID- 26378648 TI - Pharmacotherapy for Nonalcoholic Fatty Liver Disease. AB - Lifestyle modifications and optimization of the management of cardiometabolic comorbidities are currently the mainstay of treatment for patients with nonalcoholic fatty liver disease. Pharmacotherapy to halt or reverse hepatic histological injury and prevent the development of end-stage liver disease is specifically offered to patients with nonalcoholic steatohepatitis (NASH) and those with advanced fibrosis. In this review, the authors discuss the state of the art of various pharmacological agents for NASH. The efficacy of vitamin E and pioglitazone is reasonably well established in a selected group of patients with NASH. Current data do not offer convincing evidence for efficacy of pentoxifylline, long-chain polyunsaturated fatty acids, angiotensin receptor blockers, metformin, or ursodeoxycholic acid. They also discuss the state of several emerging agents for treating NASH including the farsenoid X receptor ligand, obeticholic acid. PMID- 26378650 TI - Overcoming barriers to HPV vaccination: A randomized clinical trial of a culturally-tailored, media intervention among African American girls. AB - Although genital HPV is the most prevalent STI in the US, rates of vaccination uptake among high-risk subgroups remain low. Investigations of vaccine compliance have mainly targeted mother-daughter dyads, which in some settings may prove difficult. This study examines an innovative culturally tailored, computer delivered media-based strategy to promote HPV vaccine uptake. Data, inclusive of sociodemographics, sexual behaviors, knowledge, attitudes, and beliefs about HPV and vaccination were collected via ACASI from 216 African American adolescent females (ages 14-18 years) seeking services in family planning and STI public health clinics in metropolitan Atlanta. Data were obtained prior to randomization and participation in an interactive media-based intervention designed to increase HPV vaccination uptake. Medical record abstraction was conducted 7 month post randomization to assess initial vaccine uptake and compliance. Participants in the intervention were more compliant to vaccination relative to a placebo comparison condition (26 doses vs. Seventeen doses; p=0.12). However, vaccination series initiation and completion were lower than the national average. Thorough evaluation is needed to better understand factors facilitating HPV vaccine uptake and compliance, particularly perceived susceptibility and the influence of the patient-provider encounter in a clinical setting. PMID- 26378651 TI - Polymorphisms in EGFR and IL28B are associated with spontaneous clearance in an HCV-infected Iranian population. AB - Although most hepatitis C virus (HCV)-infected individuals develop chronic infection, about 25% of them are able to clear the virus spontaneously without any therapeutic intervention. The aim of the present study was to identify genes associated with spontaneous HCV clearance in a population of Iranian patients. We genotyped 110 single-nucleotide polymorphisms (SNPs) in 59 selected--candidate- genes in a cohort of 107 HCV-infected participants who spontaneously cleared the infection and 176 participants whose infection persisted. Three out of the 110 SNPs were found to be associated with HCV outcome (P-values<0.03). rs11506105 in EGFR (epidermal growth factor receptor gene), and rs11881222 and rs12979860 in IL28B (interferon-lambda3 gene). Multivariate logistic regression of the three markers showed that the A/A genotypes in both rs11506105 (EFGR) and rs11881222 (IL28B), and the C/C genotype in rs12979860 (IL28B) are associated with HCV clearance (recessive model: odds ratio (OR)=2.06, 95% confidence interval (95% CI)=1.09-3.88, P=0.025; OR=2.09, 95% CI=1.23-3.60, P=0.007; and OR=1.95, 95% CI=1.15-3.35, P=0.014 for rs11506105, rs12979860 and rs11881222, respectively). In conclusion, EGFR and IL28B SNPs are strong independent predictive markers of spontaneous viral clearance. PMID- 26378653 TI - A functional AT/G polymorphism in the 5'-untranslated region of SETDB2 in the IgE locus on human chromosome 13q14. AB - The immunoglobulin E (IgE)-associated locus on human chromosome 13q14 influencing asthma-related traits contains the genes PHF11 and SETDB2. SETDB2 is located in the same linkage disequilibrium region as PHF11 and polymorphisms within SETDB2 have been shown to associate with total serum IgE levels. In this report, we sequenced the 15 exons of SETDB2 and identified a single previously ungenotyped mutation (AT/G, rs386770867) in the 5'-untranslated region of the gene. The polymorphism was found to be significantly associated with serum IgE levels in our asthma cohort (P=0.0012). Electrophoretic mobility shift assays revealed that the transcription factor Ying Yang 1 binds to the AT allele, whereas SRY (Sex determining Region Y) binds to the G allele. Allele-specific transcription analysis (allelotyping) was performed in 35 individuals heterozygous for rs386770867 from a panel of 200 British families ascertained through probands with severe stage 3 asthma. The AT allele was found to be significantly overexpressed in these individuals (P=1.26*10(-21)). A dual-luciferase assay with the pGL3 luciferase reporter gene showed that the AT allele significantly affects transcriptional activities. Our results indicate that the IgE-associated AT/G polymorphism (rs386770867) regulates transcription of SETDB2. PMID- 26378654 TI - Catalytic Formation of alpha-Aryl Ketones by C-H Functionalization with Cyclic Alkenyl Carbonates and One-Pot Synthesis of Isocoumarins. AB - We report here a method for direct catalytic introduction of simple alpha acylalkyl groups via rhodium-catalyzed C-H functionalization with cyclic alkenyl carbonates, synthetic equivalents to enolates bearing leaving groups. The reaction proceeded smoothly without using bases to give alpha-aryl ketones in high yields. Various nitrogen-containing aromatic rings and amide groups serve as directing groups. 3-Substituted isocoumarins can also be prepared by one-pot C-H functionalization/cyclization. PMID- 26378655 TI - Diurnal changes of biochemical metabolic markers in healthy young males - the Bispebjerg study of diurnal variations. AB - BACKGROUND: To examine whether time of the day has an effect on the circulating levels of metabolism parameters. METHODS: Venous blood samples were obtained under standardized conditions from 24 healthy young men every third hour through 24 hours. The metabolic markers and melatonin were examined at each time-point and data were analyzed by rhythmometric statistical methods. RESULTS: The normal 24-h rhythms of the participants were confirmed by significant oscillation of melatonin (p < 0.0001). Cosinor analysis revealed significant diurnal 24-h rhythms of five of the seven examined markers: Total cholesterol (p = 0.01, amplitude (amp) = 0.18 mmol/L) peaking in the early afternoon, Glucose (p < 0.0001, amp = 0.35 mmol/L) peaking around midnight, C-peptide (p < 0.001, amp = 360 pmol/L), triglyceride (p < 0.0001, amp = 0.37 mmol/L) peaking in the afternoon and low-density lipoprotein cholesterol (p = 0.003, amp = 0.16 mmol/L) peaking in the morning. C-peptide, triglyceride, and glucose had the highest 24-h oscillations in proportion to the reference ranges of the parameters for healthy young men. Glycated haemoglobin (HbA1c) (p = 0.07, amp = 0.57 mmol/L) and high density lipoprotein (p = 0.09, amp = 0.06 mmol/L) did not show significant oscillations. CONCLUSIONS: When diagnosing and monitoring metabolic disorders compensation for the 24-h variation of the biochemical metabolic markers is needed especially C-peptide, triglyceride and glucose. Furthermore, the stable HbA1c level through 24 h makes it an accurate diagnostic test for diabetes mellitus. PMID- 26378652 TI - Multifaceted role of beta-arrestins in inflammation and disease. AB - Arrestins are intracellular scaffolding proteins known to regulate a range of biochemical processes including G protein-coupled receptor (GPCR) desensitization, signal attenuation, receptor turnover and downstream signaling cascades. Their roles in regulation of signaling network have lately been extended to receptors outside of the GPCR family, demonstrating their roles as important scaffolding proteins in various physiological processes including proliferation, differentiation and apoptosis. Recent studies have demonstrated a critical role for arrestins in immunological processes including key functions in inflammatory signaling pathways. In this review, we provide a comprehensive analysis of the different functions of the arrestin family of proteins especially related to immunity and inflammatory diseases. PMID- 26378656 TI - Occurrence and Removal of Organic Micropollutants in Landfill Leachates Treated by Electrochemical Advanced Oxidation Processes. AB - In recent years, electrochemical advanced oxidation processes have been shown to be an effective alternative for the removal of refractory organic compounds from water. This study is focused on the effective removal of recalcitrant organic matter (micropollutants, humic substances, etc.) present in municipal solid waste landfill leachates. A mixture of eight landfill leachates has been studied by the electro-Fenton process using a Pt or boron-doped diamond (BDD) anode and a carbon felt cathode or by the anodic oxidation process with a BDD anode. These processes exhibit great oxidation ability due to the in situ production of hydroxyl radicals ((*)OH), a highly powerful oxidizing species. Both electrochemical processes were shown to be efficient in the removal of dissolved total organic carbon (TOC) from landfill leachates. Regarding the electro-Fenton process, the replacement of the classical anode Pt by the anode BDD allows better performance in terms of dissolved TOC removal. The occurrence and removal yield of 19 polycyclic aromatic hydrocarbons, 15 volatile organic compounds, 7 alkylphenols, 7 polychlorobiphenyls, 5 organochlorine pesticides, and 2 polybrominated diphenyl ethers in landfill leachate were also investigated. Both electrochemical processes allow one to reach a quasicomplete removal (about 98%) of these organic micropollutants. PMID- 26378657 TI - An automated optimization tool for high-dose-rate (HDR) prostate brachytherapy with divergent needle pattern. AB - Focal high-dose-rate (HDR) for prostate cancer has gained increasing interest as an alternative to whole gland therapy as it may contribute to the reduction of treatment related toxicity. For focal treatment, optimal needle guidance and placement is warranted. This can be achieved under MR guidance. However, MR guided needle placement is currently not possible due to space restrictions in the closed MR bore. To overcome this problem, a MR-compatible, single-divergent needle-implant robotic device is under development at the University Medical Centre, Utrecht: placed between the legs of the patient inside the MR bore, this robot will tap the needle in a divergent pattern from a single rotation point into the tissue. This rotation point is just beneath the perineal skin to have access to the focal prostate tumor lesion. Currently, there is no treatment planning system commercially available which allows optimization of the dose distribution with such needle arrangement. The aim of this work is to develop an automatic inverse dose planning optimization tool for focal HDR prostate brachytherapy with needle insertions in a divergent configuration. A complete optimizer workflow is proposed which includes the determination of (1) the position of the center of rotation, (2) the needle angulations and (3) the dwell times. Unlike most currently used optimizers, no prior selection or adjustment of input parameters such as minimum or maximum dose or weight coefficients for treatment region and organs at risk is required. To test this optimizer, a planning study was performed on ten patients (treatment volumes ranged from 8.5 cm(3)to 23.3 cm(3)) by using 2-14 needle insertions. The total computation time of the optimizer workflow was below 20 min and a clinically acceptable plan was reached on average using only four needle insertions. PMID- 26378658 TI - Down-regulation of SOSTDC1 promotes thyroid cancer cell proliferation via regulating cyclin A2 and cyclin E2. AB - Sclerostin domain containing protein 1 (SOSTDC1) is down-regulated and acts as a tumor suppressor in some kinds of cancers. However, the expression pattern and biological significance of SOSTDC1 in thyroid cancer are largely unknown. We demonstrated that SOSTDC1 was significantly down-regulated in thyroid cancer. Ectopic over-expression of SOSTDC1 inhibited proliferation and induced G1/S arrest in thyroid cancer cells. Moreover, SOSTDC1 over-expression suppressed the growth of tumor xenografts in nude mice. We also found that elevated SOSTDC1 led to inhibition of cyclin A2 and cyclin E2. Together,our results demonstrate that SOSTDC1 is down-regulated in thyroid cancer and might be a potential therapeutic target in the treatment of thyroid cancer. PMID- 26378660 TI - Self-Assembly of Russian Doll Concentric Porphyrin Nanorings. AB - Electronic communication between concentric macrocycles with wave functions that extend around their circumferences can lead to remarkable behavior, as illustrated by multiwalled carbon nanotubes and photosynthetic chlorophyll arrays. However, it is difficult to hold one pi-conjugated molecular ring inside another. Here, we show that ring-in-ring complexes, consisting of a 6-porphyrin ring locked inside a 12-porphyrin ring, can be assembled by placing different metals in the two rings (zinc and aluminum). A bridging ligand with carboxylate and imidazole binding sites forms spokes between the two rings, resulting in a highly cooperative supramolecular self-assembly process. Excitation is transferred from the inner 6-ring to the outer 12-ring of this Russian doll complex within 40 ps. These complexes lead to a form of template-directed synthesis in which one nanoring promotes formation of a larger concentric homologous ring; here, the effective template is an eight-component noncovalent assembly. Russian doll templating provides a new approach to amplifying the size of a covalent nanostructure. PMID- 26378659 TI - Mutation of cysteine 46 in IKK-beta increases inflammatory responses. AB - Activation of IkappaB kinase beta (IKK-beta) and nuclear factor (NF)-kappaB signaling contributes to cancer pathogenesis and inflammatory disease; therefore, the IKK-beta-NF-kappaB signaling pathway is a potential therapeutic target. Current drug design strategies focus on blocking NF-kappaB signaling by binding to specific cysteine residues on IKK-beta. However, mutations in IKK-beta have been found in patients who may eventually develop drug resistance. For these patients, a new generation of IKK-beta inhibitors are required to provide novel treatment options. We demonstrate in vitro that cysteine-46 (Cys-46) is an essential residue for IKK-beta kinase activity. We then validate the role of Cys 46 in the pathogenesis of inflammation using delayed-type hypersensitivity (DTH) and an IKK-beta C46A transgenic mouse model. We show that a novel IKK-beta inhibitor, dihydromyricetin (DMY), has anti-inflammatory effects on WT DTH mice but not IKK-beta C46A transgenic mice. These findings reveal the role of Cys-46 in the promotion of inflammatory responses, and suggest that Cys-46 is a novel drug-binding site for the inhibition of IKK-beta. PMID- 26378661 TI - Pharmacokinetics of Compounded Intravenous and Oral Gabapentin in Hispaniolan Amazon Parrots ( Amazona ventralis ). AB - Neuropathic pain is a manifestation of chronic pain that arises with damage to the somatosensory system. Pharmacologic treatment recommendations for alleviation of neuropathic pain are often multimodal, and the few reports communicating treatment of suspected neuropathic pain in avian patients describe the use of gabapentin as part of the therapeutic regimen. To determine the pharmacokinetics of gabapentin in Hispaniolan Amazon parrots ( Amazona ventralis ), compounded gabapentin suspensions were administered at 30 mg/kg IV to 2 birds, 10 mg/kg PO to 3 birds, and 30 mg/kg PO to 3 birds. Blood samples were collected immediately before and at 9 different time points after drug administration. Plasma samples were analyzed for gabapentin concentration, and pharmacokinetic parameters were calculated with both a nonlinear mixed-effect approach and a noncompartmental analysis. The best compartmental, oral model was used to simulate the concentration-time profiles resulting from different dosing scenarios. Mild sedation was observed in both study birds after intravenous injection. Computer simulation of different dosing scenarios with the mean parameter estimates showed that 15 mg/kg every 8 hours would be a starting point for oral dosing in Hispaniolan Amazon parrots based on effective plasma concentrations reported for human patients; however, additional studies need to be performed to establish a therapeutic dose. PMID- 26378662 TI - Thromboelastography Values in Hispaniolan Amazon Parrots ( Amazona ventralis ): A Pilot Study. AB - Thromboelastography (TEG) provides a global assessment of coagulation, including the rate of clot initiation, clot kinetics, achievement of maximum clot strength, and fibrinolysis. Thromboelastography (TEG) is used with increasing frequency in the field of veterinary medicine, although its usefulness in avian species has not been adequately explored. The purpose of this preliminary study was to assess the applicability of TEG in psittacine birds. Kaolin-activated TEG was used to analyze citrated whole blood collected routinely from 8 healthy adult Hispaniolan Amazon parrots ( Amazona ventralis ). The minimum and maximum TEG values obtained included time to clot initiation (2.6-15 minutes), clot formation time (4.3-20.8 minutes), alpha angle (12.7 degrees -47.9 degrees ), maximum amplitude of clot strength (26.3-46.2 mm), and percentage of lysis 30 minutes after achievement of maximum amplitude (0%-5.3%). The TEG values demonstrated comparative hypocoagulability relative to published values in canine and feline species. Differences may be explained by either the in vitro temperature at which TEG is standardly performed or the method of activation used in this study. Although TEG may have significant advantages over traditional coagulation tests, including lack of need for species-specific reagents, further evaluation is required in a variety of avian species and while exploring various TEG methodologies before this technology can be recommended for use in clinical cases. PMID- 26378663 TI - Comparison of a Point-of-Care Glucometer and a Laboratory Autoanalyzer for Measurement of Blood Glucose Concentrations in Domestic Pigeons ( Columba livia domestica). AB - Biochemical analysis is necessary for diagnosis and monitoring of diseases in birds; however, the small volume of blood that can be safely obtained from small avian species often limits laboratory diagnostic testing. Consequently, a suitable methodology requiring only a small volume of blood must be used. This study was designed to compare blood glucose concentrations in domestic pigeons ( Columba livia domestica) as measured by a commercial, handheld, human glucometer and a standard autoanalyzer. During the first phase of the study, whole blood samples obtained from 30 domestic pigeons were used to measure the blood glucose concentration with a glucometer, the packed cell volume (PCV), and the total erythrocyte count (nRBC). Plasma separated from the each sample was then used to obtain the plasma glucose concentration with the autoanalyzer. During the second phase of the study, 30 pigeons were assigned to 2 equal groups (n = 15). Hypoglycemia or hyperglycemia was induced in each group by intravenous injection of insulin or glucose, respectively. Blood was collected and processed, and glucose concentrations, PCV, and nRBC were measured as previously described. Linear-regression models demonstrated a significant relationship between results measured by the glucometer and autoanalyzer results from normoglycemic (correlation coefficient [R] = 0.43, P = .02), hypoglycemic (R = 0.95; P < .001), and hyperglycemic (R = 0.81; P < .001) birds. The results of this study suggest that we can predict the real blood-glucose concentration of pigeons by using results obtained by a glucometer. PMID- 26378664 TI - Hematologic and Total Plasma Protein Values in Free-Living Red-tailed Amazon Parrot Nestlings (Amazona brasiliensis) in Parana State, Brazil. AB - The red-tailed Amazon parrot (Amazona brasiliensis) is an endangered psittacid species that is endemic in the south and southeast Brazilian Atlantic coastal region. Hematologic evaluation is important to monitor the health of these birds, and information about laboratory values for this species is scarce. Hematologic and total plasma protein profiles were determined for 33 free-living nestling parrots in Parana state, Brazil. Parrots were temporarily removed from the nest and manually restrained to record body weight and collect blood samples. Mean body weight was <400 g in 13 birds (group 1) and >400 g in 20 birds (group 2). Significantly higher levels of mean corpuscular hemoglobin concentrations, white blood cell counts, monocytes, and basophils were observed in younger birds (group 1). A stress leukogram (high white blood cell and heterophil count) was found in all nestlings, suggesting stress induced by capture and restraint. Parameters obtained in this study will be essential to assess the physiologic and pathologic condition of wild parrots, to evaluate the effects of environmental changes on their health, and to contribute to conservation efforts of this endangered species. PMID- 26378665 TI - Comparison of Serum Protein Electrophoresis Values in Wild and Captive Whooping Cranes ( Grus americana ). AB - Protein electrophoresis of serum samples from endangered, wild whooping cranes ( Grus americana ) was performed to help assess the health of the only self sustaining, migratory population in North America. Serum samples from wild adult cranes (n = 22) were taken at Aransas National Wildlife Refuge, Texas, USA during winter. Wild juvenile cranes (n = 26) were sampled at Wood Buffalo National Park, Northwest Territories, Canada, in midsummer. All captive crane samples were acquired from the International Crane Foundation, Baraboo, WI, USA. Captive adult cranes (n = 30) were sampled during annual examinations, and archived serum samples from captive juvenile cranes (n = 19) were selected to match the estimated age of wild juveniles. Wild juveniles had significantly lower concentrations of all protein fractions than wild adults, except for prealbumin and gamma globulins. All protein fraction concentrations for wild juveniles were significantly lower compared with captive juveniles, except for prealbumin and gamma globulins, which were higher. Wild adults had significantly greater gamma globulin concentrations than captive adults. Captive juveniles had significantly lower prealbumin and albumin concentrations and albumin : globulin ratios than captive adults. The higher gamma globulin concentrations in wild versus captive cranes are likely because of increased antigenic exposure and immune stimulation. Protein fraction concentrations vary significantly with age and natural history in this species. Reference intervals for serum protein electrophoresis results from captive adult whooping cranes are provided in this study. PMID- 26378666 TI - Impact of Delayed Analysis in Avian Blood Biochemical Values Measured With the Abaxis VetScan VS2. AB - For biochemical analysis with a point-of-care biochemical analyzer, standard procedure is to analyze the sample as rapidly as possible (<1 hour) after venipuncture to minimize any changes in analyte concentrations that might occur over time. However, under some circumstances, such as when collecting blood at remote field sites, a longer delay may be unavoidable. This study evaluates the effect of delayed analysis time under unrefrigerated conditions on avian (psittacine) biochemical analyte concentrations obtained with the VetScan VS2 using Avian/Reptilian Profile Plus rotors. Venipuncture was performed on a group of 36 psittacine birds as part of routine health checks in a research aviary (Texas A&M University, College of Veterinary Medicine, College Station, TX, USA). Whole blood was kept at room temperature and analyzed at 4 time intervals: <1, 3, 6, and 24 hours after venipuncture. At 3 hours or less after collection, most biochemical parameters changed by <2%, with the exception of phosphorus (decrease of about -9%). Major increases by 24 hours after collection were observed in phosphorus (+67%) and potassium (+103%) concentrations, whereas aspartate aminotransferase (AST), uric acid, glucose, and sodium concentrations also showed statistically significant changes. Our results suggest that accurate information from analyses using the VetScan VS2 may be obtained for up to 3 hours after venipuncture without refrigeration, but researchers and clinicians do need to exercise care when interpreting blood chemistry analyte concentrations obtained after multihour delays between venipuncture and sample analysis. PMID- 26378667 TI - Metronomic Chemotherapy for Myxosarcoma Treatment in a Kori Bustard (Ardeotis kori). AB - A 22-year-old, wild-caught male kori bustard (Ardeotis kori) developed a large, slow-growing subcutaneous mass over the keel. The mass was surgically debulked and histopathologically described as a myxosarcoma. Surgical dehiscence and concurrent local tumor regrowth, with no evidence of metastasis, occurred over the subsequent 3 months, necessitating 2 additional surgical procedures to close the wound. At 19 weeks after the initial procedure, a second debulking surgical procedure was performed, at which time carboplatin-impregnated matrix beads were placed in the lesion. Moderate local tumor regrowth was clinically appreciable 4 weeks after surgery, at which time an oral metronomic chemotherapeutic protocol consisting of daily cyclophosphamide (10 mg/m(2)) and meloxicam (0.1 mg/kg) was initiated. Four months later, the tumor was no longer palpable. While oral therapy was discontinued during the breeding season, mass regrowth was observed, and the mass was surgically debulked before reinitiating oral chemotherapy. Treatment was extended for over 1 year with no hematologic evaluation or serum biochemical abnormalities, and the bird otherwise remained clinically healthy. To our knowledge, this is the first report of a myxosarcoma in a bustard species and the first report of successful clinical application of metronomic chemotherapy in an avian species. PMID- 26378668 TI - Vertebral Osteomyelitis and Septic Arthritis Associated With Staphylococcus hyicus in a Juvenile Peregrine Falcon ( Falco peregrinus ). AB - A 6-week-old, parent-reared peregrine falcon ( Falco peregrinus ) was presented with spastic hypertonus of its hind limbs of unknown origin and duration. Radiologic examination revealed smooth periosteal reactions ventrally at thoracic vertebrae 5 to 7. Contrast-enhanced computed tomography identified the swelling as inflammation; antibiotic, antimycotic, anti-inflammatory, and analgesic treatments were initiated, and vitamins and minerals were supplemented. Because the bird's condition did not improve after 10 days, it was euthanatized and submitted for postmortem examination. On histopathologic examination, chronic, active osteomyelitis was diagnosed in thoracic vertebrae 5 to 7, and chronic, active arthritis was present in both the right shoulder and left elbow joints. Staphylococcus hyicus was isolated from these 3 locations, as well as from lungs and liver, indicating a chronic septic staphylococcosis. Although infections with Staphylococcus species are occasional causes of vertebral osteomyelitis in juvenile poultry with active growth plates, it is only sporadically reported in raptors and companion birds. This case report is the first description of the clinical features and diagnostic and pathologic findings in a juvenile peregrine falcon with hematogenous osteomyelitis and arthritis associated with septicemia caused by S hyicus. PMID- 26378669 TI - Use of Deslorelin Acetate Implants to Mitigate Aggression in Two Adult Male Domestic Turkeys (Meleagris gallopavo) and Correlating Plasma Testosterone Concentrations. AB - Two adult, male domestic turkeys were treated with implants of deslorelin acetate, a gonadotropin-releasing hormone agonist, to reduce intermale aggression and aggression directed toward the animal care team at a zoologic institution. The turkeys were manually restrained and either two 4.7-mg or two 9.4-mg implants were placed within the pectoral musculature on 3 occasions over the course of approximately 1.5 years. Plasma testosterone concentrations were measured by radioimmunoassay every 2 weeks for the first month after a new implant placement and then monthly thereafter. Testosterone concentrations remained low and aggressive behavior was decreased for a period of several months after implant placement. At necropsy of both birds, no adverse gross or histologic lesions were noted at the implantation sites in the pectoral musculature or within the gonadal tissue. Deslorelin acetate implants are a treatment modality to consider for mitigation of aggression in male domestic turkeys. PMID- 26378670 TI - Mange Caused by a Novel Micnemidocoptes Mite in a Golden Eagle ( Aquila chrysaetos ). AB - A second-year, female golden eagle ( Aquila chrysaetos ) was live trapped in northern California because of severe feather loss and crusting of the skin on the head and legs. On physical examination, the bird was lethargic, dehydrated, and thin, with severe feather loss and diffuse hyperemia and crusting on the head, ventral wings, ventrum, dorsum, and pelvic limbs. Mites morphologically similar to Micnemidocoptes derooi were identified with scanning electron microscopy. The eagle was treated with ivermectin (0.4 mg/kg) once weekly for 7 weeks, as well as pyrethrin, meloxicam, ceftiofur crystalline free acid, and voriconazole. Although the eagle's condition improved, and live mites or eggs were not evident on skin scrapings at the time of completion of ivermectin treatment, evidence of dead mites and mite feces were present after the last dose of ivermectin. Two additional doses of ivermectin and 2 doses of topical selamectin (23 mg/kg) were administered 2 and 4 weeks apart, respectively. No mite eggs, feces, or adults were evident after treatment was completed. A second golden eagle found in the same region was also affected with this mite but died soon after presentation. This is the first report, to our knowledge, of successful treatment, as well as treatment with selamectin, of mites consistent with Micnemidocoptes species in any raptorial species. PMID- 26378671 TI - Use of a Nitinol Wire Stent for Management of Severe Tracheal Stenosis in an Eclectus Parrot (Eclectus roratus). AB - A 25-year-old, female eclectus parrot (Eclectus roratus) presented for dyspnea 3 weeks after anesthesia and surgery for egg yolk coelomitis. Radiography, computed tomography, and tracheoscopy revealed multiple tracheal strictures spanning a length of 2.6 cm in the mid to distal trachea. Histopathologic examination revealed mild fibrosis, inflammation, and hyperplasia consistent with acquired tracheal strictures. Tracheal resection was not considered possible because of the length of the affected trachea. The strictures were resected endoscopically, and repeated balloon dilation under fluoroscopic guidance over the course of 10 months resulted in immediate but unsustained improvement. Computed tomography was used to measure the stenotic area. A 4 * 36-mm, custom-made, nitinol wire stent was inserted into the trachea under fluoroscopic guidance. After stent placement, intermittent episodes of mild to moderate dyspnea continued, and these responded to nebulization with a combination of saline, acetylcysteine, and dexamethasone. Multiple attempts to wean the patient off nebulization therapy and to switch to a corticosteroid-free combination were unsuccessful. The parrot eventually developed complications, was euthanatized, and necropsy was performed. Histologically, the tracheal mucosa had widespread erosion to ulceration, with accumulation of intraluminal exudate and bacteria, severe degeneration of skeletal muscle and tracheal rings, prominent fibrosis, and mild to moderate, submucosal inflammation. Clinicopathologic findings in this case suggested tracheomalacia, which has not been previously described in birds. Custom-made tracheal stents can be used for severe tracheal stenosis in birds when tracheal resection and anastomosis is not possible. Complications of tracheal stent placement in birds may include tracheitis and tracheomalacia. To our knowledge, this is the first report of tracheal stent placement in an avian species. PMID- 26378672 TI - A Capture to Remember: Monitoring the Health of Avian Scavengers on the Pacific Coast. AB - Because of concern over risks to the health of avian communities on the Washington and Oregon coasts, the nonprofit Coastal Raptors and other partners initiated a study where, to date, Coastal Raptors has live-captured and sampled 27 bald eagles (Haliaeetus leucocephalus), 27 turkey vultures (Cathartes aura), and 6 common ravens (Corvus corax) for contaminants and disease study. In this article, the author highlights the events of one of the nearly 100 days on which trapping has occurred. An adult bald eagle was captured north of Ocean Shores, WA, USA, and the trapping team was visited by Quinault Indian Nation members. PMID- 26378673 TI - New Graduates - What it Takes to Become an Associate. PMID- 26378674 TI - What Is Your Diagnosis? Avian poxvirus infection and secondary candidiasis and bacterial infection. PMID- 26378678 TI - Repetitive Immunoassay with a Surface Acoustic Wave Device and a Highly Stable Protein Monolayer for On-Site Monitoring of Airborne Dust Mite Allergens. AB - This work describes a sensor to be incorporated into the on-site monitoring system of airborne house dust mite (HDM) allergens. A surface acoustic wave (SAW) device was combined with self-assembled monolayers of a highly stable antibody capture protein on the SAW surface that have high resistance to pH change. A sandwich assay was used to measure a HDM allergen, Der f 1 derived from Dermatophagoides farinae. Capture antibodies were cross-linked to a protein G based capture layer (ORLA85) on the sensor surface, thereby only Der f 1 and detection antibodies were regenerated by changing pH, resulting in fast repetition of the measurement. The sensor was characterized through 10 repetitive measurements of Der f 1, which demonstrated high reproducibility of the sensor with the coefficient of variation of 5.6%. The limit of detection (LOD) of the sensor was 6.1 ng.mL(-1), encompassing the standard (20 ng.mL(-1)) set by the World Health Organization. Negligible sensor outputs were observed for five different major allergens including other HDM allergens which tend to have cross reactivity to Der f 1 and their mixtures with Der f 1. Finally, the sensor lifetime was evaluated by conducting three measurements per day, and the sensor output did not substantially change for 4 days. These characteristics make the SAW immunosensor a promising candidate for incorporation into on-site allergen monitoring systems. PMID- 26378679 TI - Determinants of pulse pressure and annual rates of change in the Atherosclerosis Risk in Communities study. AB - INTRODUCTION: The aim of this study was to examine the effect of vascular and lifestyle risk factors on the annual rate of change in pulse pressure (PP) in a biracial, middle-aged cohort. METHODS AND RESULTS: The study population, drawn from the Atherosclerosis Risk in Communities (ARIC) cohort, included 10, 071 participants, aged 45-64 years at baseline, with a complete set of SBP and DBP readings at each of four visits 3 years apart. The average annual increase in PP was 1.23 mmHg [standard error (SE 0.01], after adjusting for baseline age differences. Compared with white men, African-American women had the highest rate of annual increase in PP (0.41 (SE 0.05) mmHg/year greater) followed by white women [0.23 (SE 0.03) mmHg/year greater] and African-American men [0.19 (SE 0.06) mmHg/year greater]. CONCLUSION: There were significant differences in both average baseline PP and average annual rate of change in PP between men and women and African-Americans and whites. Diabetes and obesity had the strongest effect on the absolute value of baseline PP and the annual rate of change in PP. PMID- 26378680 TI - Differential response to endothelial epithelial sodium channel inhibition ex vivo correlates with arterial stiffness in humans. AB - OBJECTIVES: Recently, the nanomechanical properties (i.e. stiffness) of endothelial cells have been identified as crucial for appropriate endothelial function. One major determinant of endothelial stiffness is the endothelial sodium channel (EnNaC). EnNaC-dependent stiffening leads to reduced nitric oxide release, which is a hallmark for endothelial dysfunction. In the current study, we hypothesized that endothelial function is directly linked to the overall function of the arterial system. METHODS: Sixty-four human ex-vivo arterial samples were collected from femoral bypass or vein-stripping procedures. Nanomechanical characteristics of ex-vivo endothelium from isolated arterial side branches were determined using atomic force microscopy. The endothelium's potential to respond to EnNaC inhibition by amiloride was defined as endothelial amiloride index. In addition, patients' arterial stiffness was determined by pulse wave velocity (PWV). RESULTS: Fifty-three percentage of the ex-vivo samples responded 'classically' to amiloride with endothelial softening, whereas 47% of the patients' samples did not. Interestingly, a lack of endothelial softening in the presence of amiloride in vitro was observed with higher frequency among samples obtained from individuals with elevated PWV. Further, an increased PWV was associated with impaired renal function and endothelial dysfunction (higher levels of von Willebrand factor). CONCLUSIONS: Here, we report differential responses of human ex-vivo vessels to amiloride. Although the mechanism of differential amiloride response is still unknown, the data indicate that drug action on endothelial function could differ strongly among patients, especially in those with a vascular end-organ damage determined by PWV. PMID- 26378681 TI - Reduced large elastic artery stiffness with regular aerobic exercise in middle aged and older adults: potential role of suppressed nuclear factor kappa B signalling. AB - OBJECTIVE: Aortic pulse-wave velocity (aPWV) increases with age and is a strong independent predictor of incident cardiovascular diseases (CVDs) in healthy middle-aged and older adults. aPWV is lower in middle-aged and older adults who perform regular aerobic exercise than in their sedentary peers. As exercise is associated with reduced systemic inflammation, we hypothesized that suppression of the pro-inflammatory transcription factor nuclear factor kappa B (NFkappaB) may mediate this process. METHODS: aPWV was measured in young sedentary [n = 10, blood pressure (BP) 108 +/- 3/59 +/- 2 mmHg; mean +/- SEM], middle-aged and older sedentary (n = 9, 124 +/- 7/73 +/- 5 mmHg) and middle-aged and older aerobic exercise-trained (n = 12, 110 +/- 4/67 +/- 2 mmHg) healthy, nonhypertensive men and women. RESULTS: Baseline aPWV increased with age [626 +/- 14 (young sedentary) vs. 859 +/- 49 (middle-aged and older sedentary) cm/s, P < 0.001] but was 20% lower in middle-aged and older trained (686 +/- 30 cm/s) than in middle aged and older sedentary (P < 0.005). Short-term (4 days x 2500-4500 mg) treatment with the NFkappaB inhibitor salsalate (randomized, placebo-controlled cross-over design) reduced aPWV (to 783 +/- 44 cm/s, P < 0.05) without changing BP (P = 0.40) or heart rate (P = 0.90) in middle-aged and older sedentary, but had no effect in young sedentary (623 +/- 19) or middle-aged and older trained (699 +/- 30). Following salsalate treatment, aPWV no longer was significantly different in middle-aged and older sedentary vs. middle-aged and older trained (P = 0.29). The reduction in aPWV with salsalate administration was inversely related to baseline (placebo) aPWV (r = -0.60, P < 0.001). CONCLUSION: These results support the hypothesis that suppressed NFkappaB signalling may partially mediate the lower aortic stiffness in middle-aged and older adults who regularly perform aerobic exercise. Because aPWV predicts incident cardiovascular events in this population, this suggests that tonic suppression of NFkappaB signalling in middle-aged and older exercising adults may potentially lower cardiovascular risk. PMID- 26378682 TI - Descriptive epidemiology of spot urine sodium-to-potassium ratio clarified close relationship with blood pressure level: the Nagahama study. AB - OBJECTIVES: We undertook descriptive epidemiology of spot urine sodium-to potassium ratio (Na/K) in a population sample to clarify the close relationship between Na/K and blood pressure level independently of potential confounding factors. METHODS: Study participants consisted of 9144 apparently healthy citizens (aged 54 +/- 13 years). All clinical parameters were obtained at baseline. RESULTS: Na/K was significantly higher in hypertensive individuals irrespective of antihypertensive medication status (normotension, 3.12 +/- 1.82; untreated hypertension 3.50 +/- 1.96; treated hypertension, 3.72 +/- 2.53). As urinary Na (beta = 0.092, P < 0.001) and K (beta = -0.050, P < 0.001) levels were inversely associated with BP, Na/K (beta = 0.118, P < 0.001) was more closely associated with BP than Na or K alone, as well as daily salt intake estimated from urinary Na (beta = 0.088, P < 0.001). Several factors were significantly associated with Na/K, namely age, sex, obesity, blood pressure, renal function, salt restriction status, serum phosphate and urinary creatinine level, and fasting period and season at urine sample collection. However, the association between Na/K and BP was independent of these factors (adjusted beta = 0.112, P < 0.001). No direct association was observed between Na/K and large arterial remodeling assessed by pulse wave analysis (P = 0.496) or retinal arteriolar morphological change (P = 0.431). Further, a genome-wide association study failed to identify any particular genotype influencing urinary Na and K levels. CONCLUSIONS: Although we clarified several factors that might affect spot urine Na/K, these relationships were not substantial enough to confound the association between urinary Na/K and BP. A simple measure of Na/K might be more representative of salt loading obtained from spot urine samples than Na excretion alone. PMID- 26378683 TI - True antihypertensive efficacy of sequential nephron blockade in patients with resistant hypertension and confirmed medication adherence. AB - OBJECTIVES: We assessed the influence of medication adherence on blood pressure (BP) control and target organ damage in a pre-specified analysis of a published trial comparing sequential nephron blockade (SNB) or sequential renin-angiotensin system blockade (SRASB) in patients with resistant hypertension. METHODS: Patients were randomized to SNB (n = 82) or SRASB (n = 82) and studied at baseline and after 12 weeks. BP was measured by ambulatory blood pressure monitoring. Carotid-femoral pulse wave velocity (PWV) was measured by applanation tonometry and left ventricular mass (LVM) by echocardiography. Low medication adherence was assessed through plasma irbesartan concentration below 20 ng/ml; urinary N-acetyl-seryl-aspartyl-lysyl-proline/creatinine ratio below 4 nmol/mmol; last medication intake before visit greater than 24 h and pill counting below 80% of theoretical intake. Medication adherence score (sum of items, max = 4) is defined as low (medication adherence score <2) or acceptable (medication adherence score >=2). RESULTS: Among 164 patients, 134 (81.7%) had acceptable medication adherence and 30 (18.3%) low medication adherence, with similar proportions in the SNB and SRASB arms. After 12 weeks, in patients with acceptable medication adherence, BP was more frequently controlled in those treated with SNB (64%), than SRASB (18%; P < 0.001). The difference in daytime SBP was -11.5 mmHg [95% confidence interval (CI) -15.4 to -7.5, P < 0.0001] in patients with acceptable medication adherence. In contrast, in patients with low medication adherence, the difference between groups was smaller and not significant (-9.4 mmHg, 95% CI -20.4 to 1.7, P = 0.09). Independently of BP changes, PWV and LVM decreased more in the SNB than in the SRASB arm when medication adherence was acceptable (-0.52 m/s, 95% CI -1.3 to -0.007, P = 0.047; and -24 g/m, 95% CI -36 to -12, P = 0.0003), whereas no significant changes were observed in low medication adherence patients. CONCLUSION: Medication adherence contributes to BP-lowering and regression of target organ damage. The differential effects of SNB and SRASB is observed in patients with acceptable medication adherence, and not in patients with low medication adherence. PMID- 26378685 TI - Development of new atherosclerotic plaque in hypertensive patients: an observational registry study from the Campania-Salute network. AB - BACKGROUND AND PURPOSE: Carotid atherosclerotic plaques (CAPs) can develop despite appropriate antihypertensive therapy. In this observational study, we assessed characteristics associated with risk of incident CAP in a large hypertensive registry. METHODS: We evaluated 2143 hypertensive patients without evidence of CAP. Incident CAP was censored at the time of the first ultrasound control in which CAP was detected. CAP was defined according to European Society of Hypertension/European Society of Cardiology guidelines. RESULTS: At a median follow-up period of 56.6 months, about one-third of patients (32%; N = 688) exhibited new CAP. Those patients were older, more frequently smokers, diabetic, more often with metabolic syndrome, chronic kidney disease (CKD), longer hypertension history, higher baseline SBP, pulse pressure (PP), fasting glucose, total cholesterol and triglycerides, greater left ventricular mass index, higher PP/stroke index ratio and carotid intima-media thickness (IMT; all P < 0.05). In treatment BP control was similar in both groups. In multivariable Cox regression, CAP was predicted by older age, diabetes, smoking habit, CKD and higher value of initial IMT (all P < 0.02), independently of BP control during follow-up, antihypertensive therapy and other confounders. CONCLUSION: In this registry of treated hypertensive patients, after adjusting for age and other confounders, risk of incident CAP did not depend on BP control and type of antihypertensive therapy, whereas it was independently related to the magnitude of initial IMT, independently of significant effect of prevalent diabetes and smoking habit. These findings suggest that antihypertensive treatment strategy to stop progression of cardiovascular disease might be difficult to achieve, once target organ damage is established. PMID- 26378684 TI - Integrated multiomics approach identifies calcium and integrin-binding protein-2 as a novel gene for pulse wave velocity. AB - BACKGROUND: Carotid-femoral pulse wave velocity (PWV) is an important measure of arterial stiffness, which is an independent predictor of cardiovascular morbidity and mortality. In this study, we used an integrated genetic, epigenetic and transcriptomics approach to uncover novel molecular mechanisms contributing to PWV. METHODS AND RESULTS: We measured PWV in 1505 healthy twins of European descendent. A genomewide association analysis was performed using standardized residual of the inverse of PWV. We identified one single-nucleotide polymorphism (rs7164338) in the calcium and integrin-binding protein-2 (CIB2) gene on chromosome 15q25.1 associated with PWV [beta = -0.359, standard error (SE) = 0.07, P = 4.8 * 10]. The same variant was also associated with increased CIB2 expression in leucocytes (beta = 0.034, SE = 0.008, P = 4.95 * 10) and skin (beta = 0.072, SE = 0.01, P = 2.35 * 10) and with hypomethylation of the gene promoter (beta = -0.899, SE = 0.098, P = 3.63 * 10). CONCLUSION: Our data indicate that reduced methylation of the CIB2 promoter in individuals carrying rs7164338 may lead to increased CIB2 expression. Given that CIB2 is thought to regulate intracellular calcium levels, an increase in protein levels may prevent the accumulation of serum calcium and phosphate, ultimately slowing down the process of vascular calcification. This study shows the power of integrating multiple omics to discover novel cardiovascular mechanisms. PMID- 26378686 TI - Does ambient temperature interact with air pollution to alter blood pressure? A repeated-measure study in healthy adults. AB - OBJECTIVES: Both low temperature and high air pollution have been associated with an increased risk of cardiovascular events, which could be predicted by increased arterial blood pressure (BP) within short periods. However, whether exposures to temperature and air pollution simultaneously may have interactive effects on BP has been unknown. We investigated this potential interaction during 460 repeated visits in 39 healthy university students in the context of traffic-related air pollution. METHODS: Study participants in the Healthy Volunteer Natural Relocation study underwent repeated BP measurements for 12 occasions under three exposure scenarios in Beijing, China, in 2010-2011. We used generalized linear mixed-effects models to estimate exposure effects. RESULTS: Decreasing temperature was associated with significant increases in BP. There were significant interactions between temperature and traffic-related air pollutants (particulate matter with an aerodynamic diameter <=2.5 MUm, organic carbon, elemental carbon and nitrogen dioxide) on BP (P < 0.05 for all interaction tests). The estimated increases in SBP and DBP were 4.9 mmHg [95% confidence interval (CI) 2.9-6.8] and 3.7 mmHg (95% CI 2.3-5.1) at high elemental carbon level (>=median), and were -1.3 mmHg (95% CI -6.3 to 3.6) and 0.7 mmHg (95% CI 2.8 to 4.2) at low elemental carbon level (=median). CONCLUSION: Low temperature and high air pollution may act synergistically to increase BP in healthy adults. Our findings may have potential implications for prevention of cardiovascular events associated with increased BP among high-risk individuals. PMID- 26378688 TI - Fabricating Polymer Canopies onto Structured Surfaces Using Liquid Scaffolds. AB - In this work, we study the use of initiated chemical vapor deposition in conjunction with liquid scaffolds to deposit polymer canopies onto structured surfaces. Liquid is applied to micropillar and microstructure surfaces to act as a scaffolding template such that the deposited polymer films take the shape of the liquid surface. Two methods for directing the location of the scaffolding liquid were examined. In the first method, high surface tension liquids rest in a Cassie-Baxter state over the structured surfaces, allowing for control over the canopy location and size by varying the position and volume of the liquid. In the second method, the structured surfaces are inverted onto a thin layer of low surface tension liquid, allowing the coverage and height of the canopy to be controlled by varying the area and thickness of the liquid layer. Although the canopies demonstrated in this study were fabricated using initiated chemical vapor deposition, the generality of our scaffolding method can easily be translated to other vapor deposition processes. PMID- 26378687 TI - Blood pressure variability predicts cardiovascular events independently of traditional cardiovascular risk factors and target organ damage: a LIFE substudy. AB - BACKGROUND: Assessment of antihypertensive treatment is normally based on the mean value of a number of blood pressure (BP) measurements. However, it is uncertain whether high in-treatment visit-to-visit BP variability may be harmful in hypertensive patients with left ventricular hypertrophy (LVH). METHODS: In 8505 patients randomized to losartan vs. atenolol-based treatment in the LIFE study, we tested whether BP variability assessed as SD and range for BP6-24 months measured at 6, 12, 18 and 24 months of treatment was associated with target organ damage (TOD) defined by LVH on ECG and urine albumin/creatinine ratio at 24 months, and predicted the composite endpoint (CEP) of cardiovascular death, nonfatal myocardial infarction (MI) or stroke occurring after 24 months (CEP = 630 events). RESULTS: In multiple regression models adjusted for mean BP6 24 months and treatment allocation, neither high BP6-24 months SD nor wide range were related to TOD at 24 months, except for a weak association between Sokolow Lyon voltage and DBP6-24 months SD and range (both beta = 0.04, P < 0.01). Independently of mean BP6-24 months, treatment allocation, TOD and baseline characteristics in Cox regression models, CEP after 24 months was associated with DBP6-24 months SD [hazard ratio per 1 mmHg increase1.04, 95% confidence interval (95% CI) 1.01-1.06, P = 0.005], range (hazard ratio 1.02, 95% CI 1.01-1.03, P = 0.004), SBP6-24 months SD (hazard ratio 1.01, 95% CI 0.99-1.02, P = 0.07) and range (hazard ratio 1.006, 95% CI 1.001-1.01, P = 0.04). Adjusted for the same factors, stroke was associated with DBP6-24 months SD (hazard ratio 1.06, 95% CI 1.02-1.10, P = 0.001), range (hazard ratio 1.03, 95% CI 1.01-1.04, P = 0.001), SBP6-24 months SD (hazard ratio 1.02, 95% CI 1.002-1.04, P = 0.04) and range (hazard ratio 1.008, 95% CI 1.001-1.02, P = 0.05), but MI was not. CONCLUSION: In LIFE patients, higher in-treatment BP6-24 months variability was independently of mean BP6-24 months associated with later CEP and stroke, but not with MI or TOD after 24 months. PMID- 26378689 TI - Deriving Second Osmotic Virial Coefficients from Equations of State and from Experiment. AB - The osmotic virial coefficients, which are measures of the effective interactions between solute molecules in dilute solution, may be obtained from expansions of the osmotic pressure or of the solute activity in powers of the solute concentration. In these expansions, the temperature is held fixed, and one additional constraint is imposed. When the additional constraint is that of fixed chemical potential of the solvent, the coefficient of the second-order term yields directly the second osmotic virial coefficient itself. Alternative constraints, such as fixed pressure, fixed solvent density, or the specification of liquid-vapor equilibrium, yield alternative measures of the solute-solute interaction, different from but related to the osmotic virial coefficient. These relations are summarized and, where new, are derived here. The coefficient in question may be calculated from equations of state in which the parameters have been obtained by fitting to other experimental properties. Alternatively, the coefficients may be calculated from direct experimental measurements of the deviations from Henry's law based on measurements of the activity of the solute in a coexisting gas phase. It is seen for propane in water as a test case that with the latter method, even with what appear to be the best available experimental data, there are still large uncertainties in the resulting second osmotic virial coefficient. With the former method, by contrast, the coefficient may be obtained with high numerical precision but then depends for its accuracy on the quality of the equation of state from which it is derived. PMID- 26378690 TI - Ferricyanide-backfilled cylindrical carbon fiber microelectrodes for in vivo analysis with high stability and low polarized potential. AB - The development of stable and reproducible methods for in vivo electrochemical monitoring of neurochemicals is of great physiological importance. In this study, we demonstrate ferricyanide-filled cylindrical carbon fiber microelectrodes (CFEs) of high stability and low polarized potential for in vivo electrochemical analysis. We first studied the voltammetric behavior of cylindrical CFEs by using a model system consisting of two separated cells each containing potassium ferricyanide (K3Fe(CN)6) or potassium ferrocyanide (K4Fe(CN)6). We observed that E1/2 values of the system were dependent on the ratio of the lengths of the cylindrical CFEs and of the concentrations of the redox species on both poles. Based on this property, we prepared the ferricyanide-backfilled cylindrical CFEs, and found that this kind of electrode exhibits a more stable current response and a lower polarized potential than the CFEs backfilled with KCl or Ru(NH3)6Cl3. Animal experiments with the ferricyanide-backfilled cylindrical CFEs demonstrate that this kind of electrode could be used for in vivo monitoring of neurochemical release with a high stability under some physiological conditions. PMID- 26378691 TI - Role of endoscopy after an acute episode of diverticulitis: analysis of a cohort of Portuguese patients from a tertiary referral center. AB - INTRODUCTION: Acute diverticulitis represents an inflammatory process originating in a colonic diverticulum. Although acute diverticulitis usually follows a benign course - uncomplicated diverticulitis (UCD), up to 25% may develop complicated diverticulitis (CD) including abscesses, fistulas, strictures, and perforation. Current guidelines recommend performing colonoscopy after an episode of acute diverticulitis to rule out colorectal cancer (CRC). However, the literature supporting this recommendation is still scarce. AIM AND METHODS: Our aim was to assess the relevance of endoscopy following an acute diverticulitis. Using a large cohort from a tertiary center, we retrospectively evaluated endoscopic and histologic findings in patients with acute diverticulitis confirmed by abdominal ultrasound or computed tomography. Findings were characterized as (a) normal endoscopy (highlighting only the presence of diverticula), (b) abnormal endoscopy with low-grade lesions, and (c) abnormal endoscopy with high-grade lesions. RESULTS: A total of 427 patients were evaluated, including 347 cases with UCD and 80 cases with CD. The prevalence of normal findings at endoscopy was 67.3%. An advanced adenoma or neoplasm was found in 23.7%. The estimated number of endoscopies required for diagnosing a CRC was 29 in UCD and 10 in CD. Increasing age and male sex were associated significantly with the presence of polyps at endoscopy. Increasing age was associated with CD and cancer. CONCLUSION: In our series, the prevalence of high-grade lesions and CRC was higher than that in other studies. In our opinion, the findings justify endoscopic evaluation, especially in older patients with CD. PMID- 26378692 TI - "You Live Life Going Forwards and Understand It Looking Backwards!" The Sixtieth Anniversary of the World Federation of Societies of Anaesthesiologists: 60 Years of Cooperation Between the International Anesthesia Research Society and the World Federation of Societies of Anaesthesiologists. PMID- 26378693 TI - Global Surgery and Anesthesia: No Longer a Pipe Dream. PMID- 26378694 TI - Words, Data, and the Weave of Narrative. PMID- 26378695 TI - Obstetric Neuraxial Anesthesia Contraindicated? Really? Time to Rethink Old Dogma. PMID- 26378696 TI - David (Propofol Wannabes) Versus Goliath (Propofol): AZD-3043 Goes Up Against the Giant! PMID- 26378697 TI - The Challenge of Studying and Improving Perioperative Teamwork, and Yes, Another Checklist. PMID- 26378698 TI - Postanesthesia Care Handovers: Context and Controversy Around Communication and Consistency. PMID- 26378700 TI - Coronary Sinus Ostial Atresia with Unroofed Coronary Sinus Precluding Retrograde Cardioplegia. PMID- 26378699 TI - Assessing the Methodology for Calculating Platelet Contribution to Clot Strength (Platelet Component) in Thromboelastometry and Thrombelastography. AB - The viscoelastic properties of blood clot have been studied most commonly using thrombelastography (TEG) and thromboelastometry (ROTEM). ROTEM-based bleeding treatment algorithms recommend administering platelets to patients with low EXTEM clot strength (e.g., clot amplitude at 10 minutes [A10] <40 mm) once clot strength of the ROTEM(r) fibrin-based test (FIBTEM) is corrected. Algorithms based on TEG typically use a low value of maximum amplitude (e.g., <50 mm) as a trigger for administering platelets. However, this parameter reflects the contributions of various blood components to the clot, including platelets and fibrin/fibrinogen. The platelet component of clot strength may provide a more sensitive indication of platelet deficiency than clot amplitude from a whole blood TEG or ROTEM(r) assay. The platelet component of the formed clot is derived from the results of TEG/ROTEM(r) tests performed with and without platelet inhibition. In this article, we review the basis for why this calculation should be based on clot elasticity (e.g., the E parameter with TEG and the CE parameter with ROTEM(r)) as opposed to clot amplitude (e.g., the A parameter with TEG or ROTEM(r)). This is because clot elasticity, unlike clot amplitude, reflects the force with which the blood clot resists rotation within the device, and the relationship between clot amplitude (variable X) and clot elasticity (variable Y) is nonlinear. A specific increment of X (DeltaX) will be associated with different increments of Y (DeltaY), depending on the initial value of X. When calculated correctly, using clot elasticity data, the platelet component of the clot can provide a valuable insight into platelet deficiency in emergency bleeding. PMID- 26378701 TI - Neuraxial Anesthesia in Parturients with Thrombocytopenia: A Multisite Retrospective Cohort Study. AB - BACKGROUND: The primary aim of this study was to estimate the risk of neuraxial hematoma associated with neuraxial anesthetic procedures in thrombocytopenic parturients. METHODS: A multicenter retrospective cohort study design was used to estimate the risk for spinal-epidural hematoma in parturients with a platelet count of <100,000/mm receiving neuraxial anesthesia and the risk of complications in thrombocytopenic parturients who receive general anesthesia. RESULTS: No cases of spinal hematoma were observed in 102 thrombocytopenic parturients receiving epidural analgesia or 71 receiving spinal anesthesia. Including data from the previous published series (total n = 499), the exact binomial 95% confidence interval for the risk of spinal-epidural hematoma was 0% to 0.6%. Given the small number of patients at each specific platelet count, the theoretical risks at individual platelet count strata are presented. Overall aggregate serious morbidity rate in women who received general anesthesia secondary to thrombocytopenia was 6.5% (95% confidence interval, 2.1%-14.5%). CONCLUSIONS: Our work supports the relative maternal safety of neuraxial anesthesia in parturients with mild thrombocytopenia and estimates the maternal complication rate associated with the avoidance of neuraxial anesthesia. Remaining uncertainties at lower platelet counts make a national "low platelet" registry critical to a more accurate assessment of the risk of epidural hematoma and would aid in standardization of anesthesia practice. PMID- 26378702 TI - Discrepancies Between Randomized Controlled Trial Registry Entries and Content of Corresponding Manuscripts Reported in Anesthesiology Journals. AB - BACKGROUND: Clinical trial registries have been created to reduce reporting bias. Study registration enables the examination of discrepancies between the original study design and the final results reported in the literature. The main objective of the current investigation is to compare the original clinical trial registrations and the corresponding published results in high-impact anesthesiology journals. Specifically, we examined the rates of major discrepancies (i.e., involving primary outcome, sample size calculation, or study intervention). METHODS: The 5 highest-impact factor anesthesiology journals (Anaesthesia, Anesthesia & Analgesia, Anesthesiology, British Journal of Anaesthesia, and Regional Anesthesia and Pain Medicine) were screened for randomized controlled trials published in 2013. A major discrepancy was defined as a difference in the content of the manuscript compared with the original entry in a clinical trial registry for at least one of the 3 areas: primary outcome, target sample size, and study intervention. The type of primary outcome discrepancy was further classified as adding/omitting measures or outcomes, downgrading/upgrading from primary to secondary outcomes, or changing the definition of the outcomes measured. RESULTS: Two hundred one articles were included in the final analysis. One hundred thirty of 201 (64%; 95% confidence interval [CI], 57%-71%) published clinical trials were not prospectively registered as recommended by the International Committee of Medical Journal Editors. Registration rates were significantly lower between studies performed in the United States, 15 of 40 (37%), compared with studies not performed in the United States, 92 of 161 (57%), P = 0.03. Fifty-two of 107 (48%; 95% CI, 39%-58%) registered trials had a major discrepancy when the published manuscript was compared with the clinical trial registration. Thirty-one of the 46 (67%; 95% CI, 51%-80%) primary outcome discrepancies had changes in the outcome with characteristics of reporting bias. CONCLUSIONS: We detected a high rate of major discrepancies between the published results and the original registered protocols for clinical trial manuscripts in high-impact anesthesiology journals. Future action to reduce the negative impact of reporting bias in the anesthesiology field is warranted. PMID- 26378703 TI - Clinical Research Methodology 1: Study Designs and Methodologic Sources of Error. AB - Clinical research can be categorized by the timing of data collection: retrospective or prospective. Clinical research also can be categorized by study design. In case-control studies, investigators compare previous exposures (including genetic and other personal factors, environmental influences, and medical treatments) among groups distinguished by later disease status (broadly defined to include the development of disease or response to treatment). In cohort studies, investigators compare subsequent incidences of disease among groups distinguished by one or more exposures. Comparative clinical trials are prospective cohort studies that compare treatments assigned to patients by the researchers. Most errors in clinical research findings arise from 5 largely distinguishable classes of methodologic problems: selection bias, confounding, measurement bias, reverse causation, and excessive chance variation. PMID- 26378704 TI - Clinical Research Methodology 2: Observational Clinical Research. AB - Case-control and cohort studies are invaluable research tools and provide the strongest feasible research designs for addressing some questions. Case-control studies usually involve retrospective data collection. Cohort studies can involve retrospective, ambidirectional, or prospective data collection. Observational studies are subject to errors attributable to selection bias, confounding, measurement bias, and reverse causation-in addition to errors of chance. Confounding can be statistically controlled to the extent that potential factors are known and accurately measured, but, in practice, bias and unknown confounders usually remain additional potential sources of error, often of unknown magnitude and clinical impact. Causality-the most clinically useful relation between exposure and outcome-can rarely be definitively determined from observational studies because intentional, controlled manipulations of exposures are not involved. In this article, we review several types of observational clinical research: case series, comparative case-control and cohort studies, and hybrid designs in which case-control analyses are performed on selected members of cohorts. We also discuss the analytic issues that arise when groups to be compared in an observational study, such as patients receiving different therapies, are not comparable in other respects. PMID- 26378705 TI - Clinical Research Methodology 3: Randomized Controlled Trials. AB - Randomized assignment of treatment excludes reverse causation and selection bias and, in sufficiently large studies, effectively prevents confounding. Well implemented blinding prevents measurement bias. Studies that include these protections are called randomized, blinded clinical trials and, when conducted with sufficient numbers of patients, provide the most valid results. Although conceptually straightforward, design of clinical trials requires thoughtful trade offs among competing approaches-all of which influence the number of patients required, enrollment time, internal and external validity, ability to evaluate interactions among treatments, and cost. PMID- 26378706 TI - Development and Implementation of Checklists for Routine Anesthesia Care: A Proposal for Improving Patient Safety. PMID- 26378707 TI - Systematic Reviews and Meta-Analyses of Randomized Controlled Trials on Perioperative Outcomes: An Urgent Need for Critical Reappraisal. PMID- 26378708 TI - The Effects of Flow Waveform on Oxygenation in Pediatric Patients. PMID- 26378709 TI - In Response. PMID- 26378710 TI - Randomization in a Crossover Design Is Not to Be a Minor Issue. PMID- 26378711 TI - In Response. PMID- 26378712 TI - Exparel(r): A New Local Anesthetic with Special Safety Concerns. PMID- 26378713 TI - Is Our US Health Care System Actually a Market-Based Economy? PMID- 26378714 TI - Acute Cholecystitis Complicated with Portal Vein Thrombosis: A Case Report and Literature Review. AB - BACKGROUND: Portal vein thrombosis (PVT) is an infrequent clinical condition usually associated with multiple etiological factors and diseases. In some cases, PVT remains undiagnosed and is incidentally detected during routine examination for a known etiology. CASE REPORT: Here, we present a rare case of portal vein thrombosis associated with acute cholecystitis in a 31-year-old man. CONCLUSIONS: Conservative treatment may be a feasible and safe approach for the management of PVT with acute cholecystitis, if treated at an early stage. Moreover, initial diagnosis based on radiological evaluation is possible only if the surgeons are familiar with this unusual condition. Therefore, a high index of suspicion is required for early diagnosis and management of patients with acute cholecystitis associated PVT. PMID- 26378716 TI - Tracking the Dynamic Relationship between Cellular Systems and Extracellular Subproteomes in Pseudomonas aeruginosa Biofilms. AB - The transition of the opportunistic pathogen Pseudomonas aeruginosa from free living bacteria into surface-associated biofilm communities represents a viable target for the prevention and treatment of chronic infectious disease. We have established a proteomics platform that identified 2443 and 1142 high-confidence proteins in P. aeruginosa whole cells and outer-membrane vesicles (OMVs), respectively, at three time points during biofilm development (ProteomeXchange identifier PXD002605). The analysis of cellular systems, specifically the phenazine biosynthetic pathway, demonstrates that whole-cell protein abundance correlates to end product (i.e., pyocyanin) concentrations in biofilm but not in planktonic cultures. Furthermore, increased cellular protein abundance in this pathway results in quantifiable pyocyanin in early biofilm OMVs and OMVs from both growth modes isolated at later time points. Overall, our data indicate that the OMVs being released from the surface of the biofilm whole cells have unique proteomes in comparison to their planktonic counterparts. The relative abundance of OMV proteins from various subcellular sources showed considerable differences between the two growth modes over time, supporting the existence and preferential activation of multiple OMV biogenesis mechanisms under different conditions. The consistent detection of cytoplasmic proteins in all of the OMV subproteomes challenges the notion that OMVs are composed of outer membrane and periplasmic proteins alone. Direct comparisons of outer-membrane protein abundance levels between OMVs and whole cells shows ratios that vary greatly from 1:1 and supports previous studies that advocate the specific inclusion, or "packaging", of proteins into OMVs. The quantitative analysis of packaged protein groups suggests biogenesis mechanisms that involve untethered, rather than absent, peptidoglycan binding proteins. Collectively, individual protein and biological system analyses of biofilm OMVs show that drug-binding cytoplasmic proteins and porins are potentially shuttled from the whole cell into the OMVs and may contribute to the antibiotic resistance of P. aeruginosa whole cells within biofilms. PMID- 26378715 TI - Species-Specific Structural and Functional Divergence of alpha-Crystallins: Zebrafish alphaBa- and Rodent alphaA(ins)-Crystallin Encode Activated Chaperones. AB - In addition to contributing to lens optical properties, the alpha-crystallins are small heat shock proteins that possess chaperone activity and are predicted to bind and sequester destabilized proteins to delay cataract formation. The current model of alpha-crystallin chaperone mechanism envisions a transition from the native oligomer to an activated form that has higher affinity to non-native states of the substrate. Previous studies have suggested that this oligomeric plasticity is encoded in the primary sequence and controls access to high affinity binding sites within the N-terminal domain. Here, we further examined the role of sequence variation in the context of species-specific alpha crystallins from rat and zebrafish. Alternative splicing of the alphaA gene in rodents produces alphaA(ins), which is distinguished by a longer N-terminal domain. The zebrafish genome includes duplicate alphaB-crystallin genes, alphaBa and alphaBb, which display divergent primary sequence and tissue expression patterns. Equilibrium binding experiments were employed to quantitatively define chaperone interactions with a destabilized model substrate, T4 lysozyme. In combination with multiangle light scattering, we show that rat alphaA(ins) and zebrafish alpha-crystallins display distinct global structural properties and chaperone activities. Notably, we find that alphaA(ins) and alphaBa demonstrate substantially enhanced chaperone function relative to other alpha-crystallins, binding the same substrate more than 2 orders of magnitude higher affinity and mimicking the activity of fully activated mammalian small heat shock proteins. These results emphasize the role of sequence divergence as an evolutionary strategy to tune chaperone function to the requirements of the tissues and organisms in which they are expressed. PMID- 26378717 TI - Cleavable Ligands Enable Uniform Close Packing in Colloidal Quantum Dot Solids. AB - Uniform close packing in colloidal quantum dot solids is critical for high optical density, high-mobility optoelectronic devices. A hybrid-ligand strategy is developed, combining the advantages of solid state and solution-phase ligand exchanges. This strategy uses a medium length thioamide ligand that is readily cleaved in a single chemical treatment, leading to quantum dot solids with uniformly packed domains 3 times larger than those observed in ligand-exchanged films. PMID- 26378719 TI - HDL: Quality or quantity? PMID- 26378718 TI - The Centers for Disease Control and Prevention's public health response to monitoring Tdap safety in pregnant women in the United States. AB - In 2010, in response to a widespread pertussis outbreak and neonatal deaths, California became the first state to recommend routine administration of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine during pregnancy. In 2011, the Advisory Committee on Immunization Practices (ACIP) followed with a similar recommendation for Tdap vaccination during pregnancy for previously unvaccinated women. In 2012, this recommendation was expanded to include Tdap vaccination of every pregnant woman during each pregnancy. These recommendations were based on urgent public health needs and available evidence on the safety of other inactivated vaccines during pregnancy. However, there were limited data on the safety of Tdap during pregnancy. In response to the new ACIP recommendations, the Centers for Disease Control and Prevention (CDC) implemented ongoing collaborative studies to evaluate whether vaccination with Tdap during pregnancy adversely affects the health of mothers and their offspring and provide the committee with regular updates. The current commentary describes the public health actions taken by CDC to respond to the ACIP recommendation to study and monitor the safety of Tdap vaccines in pregnant women and describes the current state of knowledge on the safety of Tdap vaccines in pregnant women. Data from the various monitoring activities support the safety of Tdap use during pregnancy. PMID- 26378720 TI - Effectiveness of Acceptance and Commitment Therapy in treating depression and suicidal ideation in Veterans. AB - OBJECTIVE: This paper examines the effects of Acceptance and Commitment Therapy for depression (ACT-D), and the specific effects of experiential acceptance and mindfulness, in reducing suicidal ideation (SI) and depression among Veterans. METHOD: Patients included 981 Veterans, 76% male, mean age 50.5 years. Depression severity and SI were assessed using the BDI-II. Experiential acceptance and mindfulness were measured with the Acceptance and Action Questionnaire-II (AAQ II) and the Five Facet Mindfulness Questionnaire, respectively. RESULTS: Of the 981 patients, 647 (66.0%) completed 10 or more sessions or finished early due to symptom relief. For Veterans with SI at baseline, mean BDI-II score decreased from 33.5 to 22.9. For Veterans with no SI at baseline, mean BDI-II score decreased from 26.3 to 15.9. Mixed models with repeated measurement indicated a significant reduction in depression severity from baseline to final assessment (b = -10.52, p < .001). After adjusting for experiential acceptance and mindfulness, patients with SI at baseline demonstrated significantly greater improvement in depression severity during ACT-D treatment, relative to patients with no SI at baseline (b = -2.81, p = .001). Furthermore, increases in experiential acceptance and mindfulness scores across time were associated with a reduction in depression severity across time (b = -0.44, p < .001 and b = -0.09, p < .001, respectfully), and the attenuating effect of mindfulness on depression severity increased across time (b = -0.05, p = .042). Increases in experiential acceptance scores across time were associated with lower odds of SI across time (odds ratio = 0.97, 95% CI [0.95, 0.99], p = .016) and the attenuating effect of experiential acceptance on SI increased across time (odds ratio = 0.96, 95% CI [0.92, 0.99], p = .023). Overall the number of patients with no SI increased from 44.5% at baseline to 65% at follow-up. CONCLUSIONS: Veterans receiving ACT-D demonstrated decreased depression severity and decreased odds of SI during treatment. Increases in experiential acceptance and mindfulness scores were associated with reduction in depression severity across time and increases in experiential acceptance scores were associated with reductions in SI across time. PMID- 26378721 TI - Biological or psychological? Effects of eating disorder psychoeducation on self blame and recovery expectations among symptomatic individuals. AB - Recent years have witnessed increasing popularity and promotion of biological influences (e.g., genetics) in eating disorder (ED) development. Although research suggests biological models of EDs reduce blame-oriented stigma in the general public, their effect on symptomatic individuals' attitudes toward themselves, treatment, and their prognosis has not been studied. Additionally, little is known about how other credible forms of conceptualizing ED development (e.g., cognitive-behavioral) affect individuals with disordered eating. Accordingly, the present study assessed the effects of three different forms of psychoeducation about ED development (biology-only, malleability of biology, cognitive-behavioral) among a sample high in ED symptoms. Participants (N = 216) viewed an audiovisual presentation describing ED development from one of the three perspectives before completing measures of self-blame for symptoms, prognostic expectations, self-efficacy in recovering, and attitudes toward a description of cognitive-behavioral therapy. There were no significant differences between conditions in self-blame. Relative to biology-only, the psychoeducational messages emphasizing malleable biology and cognitive-behavioral factors produced more prognostic optimism and self-efficacy in recovering. Perceived credibility of cognitive-behavioral therapy and expectations for its efficacy were highest in the cognitive-behavioral psychoeducation condition. Implications for efforts to educate the public and treatment-seeking individuals about the nature of EDs are discussed. PMID- 26378722 TI - Assessment of the emissions and air quality impacts of biomass and biogas use in California. AB - It is estimated that there is sufficient in-state "technically" recoverable biomass to support nearly 4000 MW of bioelectricity generation capacity. This study assesses the emissions of greenhouse gases and air pollutants and resulting air quality impacts of new and existing bioenergy capacity throughout the state of California, focusing on feedstocks and advanced technologies utilizing biomass resources predominant in each region. The options for bioresources include the production of bioelectricity and renewable natural gas (NG). Emissions of criteria pollutants and greenhouse gases are quantified for a set of scenarios that span the emission factors for power generation and the use of renewable natural gas for vehicle fueling. Emissions are input to the Community Multiscale Air Quality (CMAQ) model to predict regional and statewide temporal air quality impacts from the biopower scenarios. With current technology and at the emission levels of current installations, maximum bioelectricity production could increase nitrogen oxide (NOx) emissions by 10% in 2020, which would cause increases in ozone and particulate matter concentrations in large areas of California. Technology upgrades would achieve the lowest criteria pollutant emissions. Conversion of biomass to compressed NG (CNG) for vehicles would achieve comparable emission reductions of criteria pollutants and minimize emissions of greenhouse gases (GHG). Air quality modeling of biomass scenarios suggest that applying technological changes and emission controls would minimize the air quality impacts of bioelectricity generation. And a shift from bioelectricity production to CNG production for vehicles would reduce air quality impacts further. From a co-benefits standpoint, CNG production for vehicles appears to provide the best benefits in terms of GHG emissions and air quality. IMPLICATIONS: This investigation provides a consistent analysis of air quality impacts and greenhouse gas emissions for scenarios examining increased biomass use. Further work involving economic assessment, seasonal or annual emissions and air quality modeling, and potential exposure analysis would help inform policy makers and industry with respect to further development and direction of biomass policy and bioenergy technology alternatives needed to meet energy and environmental goals in California. PMID- 26378723 TI - Digging up the recent Spanish memory: genetic identification of human remains from mass graves of the Spanish Civil War and posterior dictatorship. AB - The Spanish Civil War (1936-1939) and posterior dictatorship (until 1970s) stands as one of the major conflicts in the recent history of Spain. It led to nearly two hundred thousand men and women executed or murdered extra-judicially or after dubious legal procedures. Nowadays, most of them remain unidentified or even buried in irretraceable mass graves across Spain. Here, we present the genetic identification of human remains found in 26 mass graves located in Northern Spain. A total of 252 post-mortem remains were analyzed and compared to 186 relatives, allowing the identification of 87 victims. Overall, a significant success of DNA profiling was reached, since informative profiles (>= 12 STRs and/or mitochondrial DNA profile) were obtained in 85.71% of the remains. This high performance in DNA profiling from challenging samples demonstrated the efficacy of DNA extraction and amplification methods used herein, given that only around 14.29% of the samples did not provide an informative genetic profile for the analysis performed, probably due to the presence of degraded and/or limited DNA in these remains. However, this study shows a partial identification success rate, which is clearly a consequence of the lack of both appropriate family members for genetic comparisons and accurate information about the victims' location. Hence, further perseverance in the exhumation of other intact graves as well as in the search of more alleged relatives is crucial in order to facilitate and increase the number of genetic identifications. PMID- 26378724 TI - Influence of prolonged static stretching on motor unit firing properties. AB - INTRODUCTION: The purpose of this study was to examine the influence of a stretching intervention on motor control strategy of the biceps brachii muscle. METHODS: Ten men performed twelve 100-s passive static stretches of the biceps brachii. Before and after the intervention, isometric strength was tested during maximal voluntary contractions (MVCs) of the elbow flexors. Subjects also performed trapezoid isometric contractions at 30% and 70% of MVC. Surface electromyographic signals from the submaximal contractions were decomposed into individual motor unit action potential trains. Linear regression analysis was used to examine the relationship between motor unit mean firing rate and recruitment threshold. RESULTS: The stretching intervention caused significant decreases in y-intercepts of the linear regression lines. In addition, linear slopes at both intensities remained unchanged. CONCLUSIONS: Despite reduced motor unit firing rates following the stretches, the motor control scheme remained unchanged. PMID- 26378725 TI - Neural correlates of episodic future thinking impairment in multiple sclerosis patients. AB - BACKGROUND: Recent clinical investigations showed impaired episodic future thinking (EFT) abilities in multiple sclerosis (MS) patients. On these bases, the aim of the current study was to explore the structural and functional correlates of EFT impairment in nondepressed MS patients. METHOD: Twenty-one nondepressed MS patients and 20 matched healthy controls were assessed with the adapted Autobiographical Interview (AI), and patients were selected on the bases of an EFT impaired score criterion. The 41 participants underwent a functional magnetic resonance imaging (fMRI) session, distinguishing the construction and elaboration phases of the experimental EFT, and the categorical control tests. Structural images were also acquired. RESULTS: During the EFT fMRI task, increased cerebral activations were observed in patients (relative to healthy controls) within the EFT core network. These neural changes were particularly important during the construction phase of future events and involved mostly the prefrontal region. This was accompanied by an increased neural response mostly in anterior, and also posterior, cerebral regions, in association with the amount of detail produced by patients. In parallel, structural measures corroborated a main positive association between the prefrontal regions' volume and EFT performance. However, no association between the hippocampus and EFT performance was observed in patients, at both structural and functional levels. CONCLUSION: We have documented significant overlaps between the structural and functional underpinnings of EFT impairment, with a main role of the prefrontal region in its clinical expression in MS patients. PMID- 26378726 TI - Thermo activated persulfate oxidation of antibiotic sulfamethoxazole and structurally related compounds. AB - The widespread occurrence of sulfonamides (e.g., sulfamethoxazole) in natural environment has raised growing concerns due to their potential to induce antibiotic-resistant genes. In this study, the degradation of SMX and related sulfonamides by thermo activated persulfate (PS) oxidation was investigated. Experimental results demonstrated that SMX degradation followed pseudo-first order reaction kinetics. The pseudo-first-order rate constant (k(obs)) was increased markedly with increasing temperature and pH. The presence of bicarbonate manifested promoting effect on SMX degradation while fulvic acid reduced it. Radical scavenging tests revealed that the predominant oxidizing species was SO4(*-) at neutral pH. Aniline moiety in SMX molecule was confirmed to be the primary reactive site for SO4(*-) attack by comparison with substructural analogues. Reaction products were enriched by solid phase extraction (SPE) and analyzed by liquid chromatography-electrospray ionization triple quadrupole mass spectrometry (LC-ESI-MS/MS). A total of 7 products derived from hydroxylation, sulfonamide S-N bond cleavage, aniline moiety oxidation and coupling reaction were identified, and transformation pathways of SMX oxidation were proposed. Degradation of sulfonamides was appreciably influenced by the heterocyclic ring present in the molecules. Results reveal that thermo activated PS oxidation could be an efficient approach for remediation of water contaminated by SMX and related sulfonamides. PMID- 26378727 TI - Microbial ureolysis in the seawater-catalysed urine phosphorus recovery system: Kinetic study and reactor verification. AB - Our previous study has confirmed the feasibility of using seawater as an economical precipitant for urine phosphorus (P) precipitation. However, we still understand very little about the ureolysis in the Seawater-based Urine Phosphorus Recovery (SUPR) system despite its being a crucial step for urine P recovery. In this study, batch experiments were conducted to investigate the kinetics of microbial ureolysis in the seawater-urine system. Indigenous bacteria from urine and seawater exhibited relatively low ureolytic activity, but they adapted quickly to the urine-seawater mixture during batch cultivation. During cultivation, both the abundance and specific ureolysis rate of the indigenous bacteria were greatly enhanced as confirmed by a biomass-dependent Michaelis Menten model. The period for fully ureolysis was decreased from 180 h to 2.5 h after four cycles of cultivation. Based on the successful cultivation, a lab scale SUPR reactor was set up to verify the fast ureolysis and efficient P recovery in the SUPR system. Nearly complete urine P removal was achieved in the reactor in 6 h without adding any chemicals. Terminal Restriction Fragment Length Polymorphism (TRFLP) analysis revealed that the predominant groups of bacteria in the SUPR reactor likely originated from seawater rather than urine. Moreover, batch tests confirmed the high ureolysis rates and high phosphorus removal efficiency induced by cultivated bacteria in the SUPR reactor under seawater-to urine mixing ratios ranging from 1:1 to 9:1. This study has proved that the enrichment of indigenous bacteria in the SUPR system can lead to sufficient ureolytic activity for phosphate precipitation, thus providing an efficient and economical method for urine P recovery. PMID- 26378728 TI - Removal of disinfection by-product precursors by coagulation and an innovative suspended ion exchange process. AB - This investigation aimed to compare the disinfection by-product formation potentials (DBPFPs) of three UK surface waters (1 upland reservoir and 2 lowland rivers) with differing characteristics treated by (a) a full scale conventional process and (b) pilot scale processes using a novel suspended ion exchange (SIX) process and inline coagulation (ILCA) followed by ceramic membrane filtration (CMF). Liquid chromatography-organic carbon detection analysis highlighted clear differences between the organic fractions removed by coagulation and suspended ion exchange. Pretreatments which combined SIX and coagulation resulted in significant reductions in dissolved organic carbon (DOC), UV absorbance (UVA), trihalomethane and haloacetic acid formation potential (THMFP, HAAFP), in comparison with the SIX or coagulation process alone. Further experiments showed that in addition to greater overall DOC removal, the processes also reduced the concentration of brominated DBPs and selectively removed organic compounds with high DBPFP. The SIX/ILCA/CMF process resulted in additional removals of DOC, UVA, THMFP, HAAFP and brominated DBPs of 50, 62, 62, 62% and 47% respectively compared with conventional treatment. PMID- 26378729 TI - Microbial population dynamics in response to increasing loadings of pre hydrolyzed pig manure in an expanded granular sludge bed. AB - In recent years, pig manure (PM) has been regarded as a valuable substrate for energy and resource recovery via bioprocesses such as anaerobic digestion (AD), however, the efficiency of digesting raw PM is limited by the presence of refractory compounds. In this study, we applied a series of pretreatment on raw PM, consisting of subsequent thermochemical pretreatment, enzymatic hydrolysis, tyndallization and filtration. The liquid PM hydrolysates were fed to an expanded granular sludge bed (EGSB) for the production of biogas. The general performance and population dynamics of the EGSB reactor were assessed during an extended operational period of 339 days. An efficient and stable digestion process was achieved under high organic loading rates (OLRs) up to 21 kg-COD/(m(3).d), agreeing with a sludge loading rate of 0.75 kg-COD/(kg-VSS.d), 1600 mg-NH4(+)-N/L and 17 mg/L of free ammonia nitrogen. The tyndallization decreased the total amount of active cells from 1 * 10(8) to 1 * 10(2) CFU/ml. Hence, bio augmentation with pigs' intestinal microbiota was absent and the community dynamics were mainly credited to the composition of the substrate (i.e. PM hydrolysates) and the environmental conditions inside the reactor. The results showed the influence of both the seed community and the imposed loading rates on the evolutionary trajectory of the EGSB microbial community. Four bacterial genera (Clostridium, Cytophaga, Bacillus and Bacteroides) and two methanogenic genera (Methanosaeta and Methanobacterium) dominated the communities. An obvious shift from aceticlastic Methanosaeta to hydrogenotrophic Methanobacterium appeared when the OLR was increased to over 10 kg-COD/(m(3).d). PMID- 26378730 TI - A novel shortcut nitrogen removal process using an algal-bacterial consortium in a photo-sequencing batch reactor (PSBR). AB - Removal of nitrogen from anaerobically digested swine manure centrate was investigated in a photo-sequencing batch reactor (PSBR) with alternating light and dark periods. Microalgal photosynthesis was shown to provide enough oxygen for complete nitritation during the light period. With addition of an organic carbon source during the dark period, the reactor removed over 90% total nitrogen (TN) without aeration other than by mixing. Overall, 80% of the TN removal was through nitritation/denitritation and the rest was due to biomass uptake. The high concentrations of ammonia and nitrite and low dissolved oxygen concentration in the PSBR effectively inhibited nitrite oxidizing bacteria, resulting in stable nitritation. The hybrid microalgal photosynthesis and shortcut nitrogen removal process has the potential to substantially reduce aeration requirements for treatment of anaerobic digestion side streams. The PSBR also produced well settling biomass with sludge volume index of 62 +/- 16 mL mg(-1). PMID- 26378731 TI - Towards reducing DBP formation potential of drinking water by favouring direct ozone over hydroxyl radical reactions during ozonation. AB - When ozonation is employed in advanced water treatment plants to produce drinking water, dissolved organic matter reacts with ozone (O3) and/or hydroxyl radicals (OH) affecting disinfection byproduct (DBP) formation with subsequently used chlorine-based disinfectants. This study presents the effects of varying exposures of O3 and *OH on DBP concentrations and their associated toxicity generated after subsequent chlorination. DBP formation potential tests and in vitro bioassays were conducted after batch ozonation experiments of coagulated surface water with and without addition of tertiary butanol (t-BuOH, 10 mM) and hydrogen peroxide (H2O2, 1 mg/mg O3), and at different pH (6-8) and transferred ozone doses (0-1 mg/mg TOC). Although ozonation led to a 24-37% decrease in formation of total trihalomethanes, haloacetic acids, haloacetonitriles, and trihaloacetamides, an increase in formation of total trihalonitromethanes, chloral hydrate, and haloketones was observed. This effect however was less pronounced for samples ozonated at conditions favoring molecular ozone (e.g., pH 6 and in the presence of t-BuOH) over *OH reactions (e.g., pH 8 and in the presence of H2O2). Compared to ozonation only, addition of H2O2 consistently enhanced formation of all DBP groups (20-61%) except trihalonitromethanes. This proves that *OH-transformed organic matter is more susceptible to halogen incorporation. Analogously, adsorbable organic halogen (AOX) concentrations increased under conditions that favor *OH reactions. The ratio of unknown to known AOX, however, was greater at conditions that promote direct O3 reactions. Although significant correlation was found between AOX and genotoxicity with the p53 bioassay, toxicity tests using 4 in vitro bioassays showed relatively low absolute differences between various ozonation conditions. PMID- 26378732 TI - Are fecal indicator bacteria appropriate measures of recreational water risks in the tropics: A cohort study of beach goers in Brazil? AB - Regulating recreational water exposure to pathogens within the tropics is a major public health and economic concern. Although numerous epidemiological studies estimating the risk to recreational marine water exposure have been conducted since the 1950s, few studies have been done in the tropics. Furthermore, many have suggested that the use of fecal indicator bacteria for monitoring recreational water quality in temperate regions is not appropriate in the tropics. We analyzed a large cohort study of five beaches in Sao Paulo, Brazil, conducted during consecutive weekends in the summer of 1999 that estimated risk to water, sand, and food exposures. Enterococci and Escherichia coli concentrations were measured each day of the study. Elevated risks were estimated for both swimming (OR = 1.36 95% CI: 1.05-1.58) and sand contact (OR = 1.29 95% CI 1.05-1.58). A 1 log increase in enterococci concentration was associated with an 11% increase in risk (OR = 1.11 95% CI: 1.04-1.19). For E. coli a 1-log increase in concentration was associated with 19% increase in risk (OR = 1.19 95% CI: 1.14-1.28). Most countries with beaches in the tropics are lower or middle income countries (LMIC) and rely on tourism as a major source of income. We present data that suggests fecal indicator bacteria such as enterococci are an appropriate indicator of risk in tropical urban settings where contamination is coming from predominantly human sources. Additional studies in tropical settings could help inform and refine guidelines for safe use of recreational waters. PMID- 26378733 TI - Better understanding of water quality evolution in water distribution networks using data clustering. AB - The complexity of water distribution networks raises challenges in managing, monitoring and understanding their behavior. This article proposes a novel methodology applying data clustering to the results of hydraulic simulation to define quality zones, i.e. zones with the same dynamic water origin. The methodology is presented on an existing Water Distribution Network; a large dataset of conductivity measurements measured by 32 probes validates the definition of the quality zones. The results show how quality zones help better understanding the network operation and how they can be used to analyze water quality events. Moreover, a statistical comparison with 158,230 conductivity measurements validates the definition of the quality zones. PMID- 26378734 TI - Regional homogeneity of spontaneous brain activity in adult patients with obsessive-compulsive disorder before and after cognitive behavioural therapy. AB - BACKGROUND: Cognitive behavioural therapy (CBT) is an effective treatment for obsessive-compulsive disorder (OCD). Several neuroimaging studies have explored alterations of brain function in OCD patients as they performed tasks after CBT. However, the effects of CBT on the neural activityin OCD during rest remain unknown. Therefore, we investigated changes in regional homogeneity (ReHo) in OCD patients before and after CBT. METHODS: Twenty-two OCD patients and 22 well matched healthy controls participated in the resting-state functional magnetic resonance imaging scans. We compared differences in ReHo between the OCD and control groups before treatment and investigated the changes of ReHo in 17 OCD patients who responded to CBT. RESULTS: Compared to healthy controls, OCD patients exhibited higher ReHo in the right orbitofrontal cortex (OFC), bilateral middle frontal cortex, right precuneus, left cerebellum, and vermis, as well as lower ReHo in the bilateral caudate, right calcarine, right posterior cingulate cortex, and right middle temporal cortex. Along with the clinical improvement in OCD patients after CBT, we found decreased ReHo in the right OFC, bilateral middle frontal cortex, left cerebellum and vermis, and increased ReHo in the left caudate. Improvement of OCD symptoms was significantly correlated with the changed ReHo in the right OFC and left cerebellum. CONCLUSIONS: Although these findings are preliminary and need to be replicated in larger samples, they indicate the presence of abnormal spontaneous brain activity of the prefrontal striatal-cerebellar circuit in OCD patients, and provide evidence that CBT can selectively modulate the spontaneous brain activity of this circuit in OCD patients. PMID- 26378735 TI - American tertiary clinic-referred bipolar II disorder compared to bipolar I disorder: More severe in multiple ways, but less severe in a few other ways. AB - BACKGROUND: Prevalence and relative severity of bipolar II disorder (BDII) vs. bipolar I disorder (BDI) are controversial. METHODS: Prevalence, demographics, and illness characteristics were compared among 260 BDII and 243 BDI outpatients referred to the Stanford University BD Clinic and assessed with the Systematic Treatment Enhancement Program for Bipolar Disorder Affective Disorders Evaluation. RESULTS: BDII vs. BDI outpatients had statistically similar prevalence (51.7% vs. 48.3%), and in multiple ways had more severe illness, having significantly more often: lifetime comorbid anxiety (70.8% vs. 58.4%) and personality (15.4% vs. 7.4%) disorders, first-degree relative with mood disorder (62.3% vs. 52.3%), at least 10 prior mood episodes (80.0% vs. 50.9%), current syndromal/subsyndromal depression (52.3% vs. 38.4%), current antidepressant use (47.3% vs. 31.3%), prior year rapid cycling (33.6% vs. 13.4%), childhood onset (26.2% vs. 16.0%), as well as earlier onset age (17.0+/-8.6 vs. 18.9+/-8.1 years), longer illness duration (19.0+/-13.0 vs. 16.1+/-13.0), and higher current Clinical Global Impression for Bipolar Disorder-Overall Severity (4.1+/-1.4 vs. 3.7+/-1.5). However, BDII vs. BDI patients significantly less often had prior psychosis (14.2% vs. 64.2%), psychiatric hospitalization (10.0% vs. 67.9%), and current prescription psychotropic use, (81.5% vs. 93.0%), and had a statistically similar rate of prior suicide attempt (29.5% vs. 32.1%). LIMITATIONS: American tertiary bipolar disorder clinic referral sample, cross-sectional design. CONCLUSIONS: Further studies are warranted to determine the extent to which BDII, compared to BDI, can be more severe in multiple ways but less severe in a few other ways, and contributors to occurrence of more severe forms of BDII. PMID- 26378736 TI - Redefining the projectional and clinical anatomy of the duodenojejunal flexure in children. AB - The duodenojejunal flexure (DJF) is an important surgical landmark that enables the pediatric surgeon to establish whether normal intestinal rotation has occurred. The degree of variation in the position of the DJF has not been studied in the pediatric population, and there have been only limited studies on adults. The aim of the present study was to determine the position and relationships of the DJF in infants and children utilizing cross-sectional imaging. Computer tomography scans of 120 children were divided into three age groups and systematically analyzed. The DJF position was measured in relation to the vertebral body level, midline, anterior-posterior distance from the vertebral body, transpyloric plane, and mesenteric vessels. The position of the third part of the duodenum and the length of the mesenteric root were also determined. There was considerable variation in the DJF position with respect to the above landmarks in all three age groups. The vertebral body level of the DJF was centered on L1, but ranged between T11 and L3. In 3% of children with normal rotation the SMA/SMV relationship was abnormal. The third part of the duodenum was consistently found to be retromesenteric. The length of the mesenteric root ranged from 7 to 22 cm, and generally lengthened with increasing age. Owing to its variable position in infants and children, the DJF on its own may not be a reliable landmark for establishing normal intestinal rotation. Assessing for normal rotation is multifaceted and further comparative studies are required to characterize the anatomical features of normal and abnormal rotation. PMID- 26378737 TI - Sex-specific differences in fetal growth in newborns exposed prenatally to traffic-related air pollution in the PELAGIE mother-child cohort (Brittany, France). AB - BACKGROUND: Numerous studies have linked prenatal traffic-related air pollution exposure to fetal growth. Recently, several studies have suggested exploring this association independently among boys and girls because of potential sex-specific biological vulnerability to air pollution. Residence-based factors can also influence fetal growth by enhancing susceptibility to the toxic effects of air pollution and must also be considered in these relations. OBJECTIVE: We examined sex-specific associations between prenatal air pollution exposure and fetal growth and explored whether they differed by the urban-rural status of maternal residence. METHODS: This study relied on the PELAGIE mother-child cohort (2521 women, Brittany, France, 2002-2006). Fetal growth was assessed through birth weight, head circumference and small weight (SGA) and small head circumference (SHC) for gestational age. Nitrogen dioxide (NO2) concentrations at mothers' homes were estimated by using a land use regression model taking into account temporal variation during pregnancy. Associations between estimated NO2 concentrations and fetal growth were assessed with linear regression or logistic regression models, depending on the outcome investigated. RESULTS: An interquartile range (8.8 ug m(-3)) increase in NO2 exposure estimates was associated with a 27.4 g (95% CI 0.8 to 55.6) increase in birth weight and a 0.09 cm (95% CI 0.00-0.17) significant increase in head circumference, among newborn boys only. Their risks of SGA and SHC were reduced (OR 0.70, 95% CI 0.53-0.92, OR 0.76, 95% CI 0.56-1.03, respectively, for an increase of 8.8 ug m(-3)). No statistically significant trends were observed among girls. Urban-rural status modified the effect of air pollution only for SHC and again only for newborn boys. CONCLUSION: Findings from this study confirm the need to consider sex specific associations between air pollution and fetal growth and to investigate possible mechanisms by which traffic-related air pollution may increase anthropometric parameters at birth. PMID- 26378738 TI - Pediatric Insomnia. AB - Insomnia in children is complex and frequently multifactorial. This review discusses the major categories of insomnia as well as common causes. The consequences of insomnia, including issues with mood, behavior, and cognition, are discussed. Sleep disorders are much more prevalent in certain pediatric populations, such as children with autism spectrum disorders. The evaluation of insomnia in children includes a focused history and examination and occasionally actigraphy or polysomnography. Behavioral and pharmacological therapies are discussed, as are future directions for research and clinical practice. PMID- 26378739 TI - Does Digital Game Interactivity Always Promote Self-Efficacy? AB - Interactive digital games can promote self-efficacy by engaging players in enactive and observational learning. However, interactivity does not always lead to greater self-efficacy. Important constructs in social cognitive theory, such as performance outcome and perceived similarity, are often not accounted for in studies that have tested the effect of digital game interactivity on self efficacy. This study assessed the effects of interactive digital games compared with passive digital games based on video comparison, a common experimental design used to test the effect of digital game interactivity on self-efficacy. In addition, this study also evaluated player performance and measured perceived similarity to the observed player. Findings suggested that in general, digital game interactivity predicted higher self-efficacy compared with noninteractive passive games. However, in the noninteractive conditions, the effects of performance on self-efficacy were moderated by perceived similarity between the observer and the observed player. When the observed player was perceived to be similar to the observer, the effects of performance on self-efficacy were comparable to the interactive game, but when the observed player was perceived as dissimilar to the observer, observing the dissimilar player failed to increase observer self-efficacy. Implications for interactivity manipulations and game developers are discussed. PMID- 26378740 TI - 1,4-Oxazine beta-Secretase 1 (BACE1) Inhibitors: From Hit Generation to Orally Bioavailable Brain Penetrant Leads. AB - 1,4-Oxazines are presented, which show good in vitro inhibition in enzymatic and cellular BACE1 assays. We describe lead optimization focused on reducing the amidine pKa while optimizing interactions in the BACE1 active site. Our strategy permitted modulation of properties such as permeation and especially P glycoprotein efflux. This led to compounds which were orally bioavailable, centrally active, and which demonstrated robust lowering of brain and CSF Abeta levels, respectively, in mouse and dog models. The amyloid lowering potential of these molecules makes them valuable leads in the search for new BACE1 inhibitors for the treatment of Alzheimer's disease. PMID- 26378742 TI - CHANGES IN REGIONAL BRAIN ACTIVATION RELATED TO DEPRESSIVE STATE: A 2-YEAR LONGITUDINAL FUNCTIONAL MRI STUDY. AB - BACKGROUND: Abnormal brain activations during processing of emotional facial expressions in depressed patients have been demonstrated. We investigated the natural course of brain activation in response to emotional faces in depression, indexed by functional magnetic resonance imaging (fMRI) scans preceding and following change in depressive state. We hypothesized a decrease in activation in the amygdala, anterior cingulate cortex (ACC), and insula with a decrease in depressive pathology. METHODS: A 2-year longitudinal fMRI study was conducted as part of the Netherlands Study of Depression and Anxiety. We included 32 healthy controls and 49 depressed patients. During the second scan, 27 patients were in remission (remitters), the other 22 were not (nonremitters). All participants viewed faces with emotional expressions during scanning. RESULTS: Rostral ACC activation during processing of happy faces was predictive of a decrease in depressive state (PFWE = .003). In addition, remitters showed decreased activation of the insula over time (PFWE = .016), specifically during happy faces. Nonremitters displayed increased abnormalities in emotion recognition circuitry during the second scan compared to the first. No effect of selective serotonin reuptake inhibitor use was observed. CONCLUSIONS: Our results demonstrate that rostral ACC activation may predict changes in depressive state even at 2-year outcome. The association between change in depressed state and change in insula activation provides further evidence for the role of the insula in a network maintaining emotional and motivational states. PMID- 26378741 TI - Anterior Ocular Toxicity of Intravitreous Melphalan for Retinoblastoma. AB - IMPORTANCE: Intravitreous injections of melphalan hydrochloride are increasingly used in the treatment of vitreous seeding of retinoblastoma. Although this technique can save eyes otherwise destined for enucleation, ocular salvage may be accompanied by local toxic effects. Posterior segment toxic effects in this context are well established. This report describes the toxic effects on the anterior segment following intravitreous administration of melphalan. OBSERVATIONS: Our clinic cohort included 76 patients who received intravitreous injections of melphalan at Memorial Sloan Kettering Cancer Center from September 12, 2012, through April 15, 2015; data analysis was performed from April 15 through May 15, 2015. We report a series of 5 patients from this cohort who developed anterior segment toxic effects. These abnormalities were found at the injection site or within the meridian of the injection and included a traumatic cataract following an injection at an outside hospital, iris depigmentation and thinning, iris recession with retinal necrosis and hypotony, a filtering conjunctival bleb, and focal scleromalacia with localized pigmentation. CONCLUSIONS AND RELEVANCE: Intravitreous injection of melphalan may result in toxic effects on the anterior segment of the eye, in addition to retinal abnormalities, and appears to be more common in the meridian of the injection where the drug concentration is highest. PMID- 26378743 TI - Anionic ordering and thermal properties of FeF3.3H2O. AB - Iron fluoride trihydrate can be used to prepare iron hydroxyfluoride with the hexagonal-tungsten-bronze (HTB) type structure, a potential cathode material for batteries. To understand this phase transformation, a structural description of beta-FeF3.3H2O is first performed by means of DFT calculations and Mossbauer spectroscopy. The structure of this compound consists of infinite chains of [FeF6]n and [FeF2(H2O)4]n. The decomposition of FeF3.3H2O induces a collapse and condensation of these chains, which lead to the stabilization, under specific conditions, of a hydroxyfluoride network FeF3-x(OH)x with the HTB structure. The release of H2O and HF was monitored by thermal analysis and physical characterizations during the decomposition of FeF3.3H2O. An average distribution of FeF4(OH)2 distorted octahedra in HTB-FeF3-x(OH)x was obtained subsequent to the thermal hydrolysis/olation of equatorial anionic positions involving F(-) and H2O. This study provides a clear understanding of the structure and thermal properties of FeF3.3H2O, a material that can potentially bridge the recycling of pickling sludge from the steel industry by preparing battery electrodes. PMID- 26378744 TI - Single-cell codetection of metabolic activity, intracellular functional proteins, and genetic mutations from rare circulating tumor cells. AB - The high glucose uptake and activation of oncogenic signaling pathways in cancer cells has long made these features, together with the mutational spectrum, prime diagnostic targets of circulating tumor cells (CTCs). Further, an ability to characterize these properties at a single cell resolution is widely believed to be essential, as the known extensive heterogeneity in CTCs can obscure important correlations in data obtained from cell population-based methods. However, to date, it has not been possible to quantitatively measure metabolic, proteomic, and genetic data from a single CTC. Here we report a microchip-based approach that allows for the codetection of glucose uptake, intracellular functional proteins, and genetic mutations at the single-cell level from rare tumor cells. The microchip contains thousands of nanoliter grooves (nanowells) that isolate individual CTCs and allow for the assessment of their glucose uptake via imaging of a fluorescent glucose analog, quantification of a panel of intracellular signaling proteins using a miniaturized antibody barcode microarray, and retrieval of the individual cell nuclei for subsequent off-chip genome amplification and sequencing. This approach integrates molecular-scale information on the metabolic, proteomic, and genetic status of single cells and permits the inference of associations between genetic signatures, energy consumption, and phosphoproteins oncogenic signaling activities in CTCs isolated from blood samples of patients. Importantly, this microchip chip-based approach achieves this multidimensional molecular analysis with minimal cell loss (<20%), which is the bottleneck of the rare cell analysis. PMID- 26378746 TI - Simplifying sample preparation using fabric phase sorptive extraction technique for the determination of benzodiazepines in blood serum by high-performance liquid chromatography. AB - Fabric phase sorptive extraction (FPSE), a recently introduced novel sample preparation technology, has been evaluated for the extraction of benzodiazepines from human blood serum. FPSE utilizes a flexible fabric surface as the substrate platform for creating sol-gel hybrid organic-inorganic sorbent coatings. FPSE media can be introduced directly into the sample containing the target analyte(s), requiring no need for prior sample pretreatment or clean-up. Benzodiazepines were selected as model analytes because they represent one of the most widely used therapeutic drugs in psychiatry and are also amongst the most frequently encountered drugs in forensic toxicology. The chromatographic separation of target analytes was performed on a LiChroCART-LiChrospher(r)100 RP 18e (5 um, 250 * 4 mm) analytical column, operated at room temperature. Ternary gradient elution was applied with a mobile phase that consisted of acetonitrile, methanol and ammonium acetate (0.05 M), which was delivered at a flow rate of 1.0 mL/min. Diode array detection was performed with monitoring at 240 nm. FPSE was performed using cellulose fabric extraction media coated with sol-gel poly(ethylene glycol) (sol-gel PEG). Absolute recovery values in the equilibrium state for the examined benzodiazepines were found to be 27% for bromazepam, 63% for lorazepam, 42 % for diazepam and 39% for alprazolam. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26378747 TI - Treatment of Retinoblastoma in 2015: Agreement and Disagreement. AB - The management of intraocular retinoblastoma is rapidly changing, and even recent reviews on the subject are behind existing practices. The 4 authors of this report collectively represent their management strategies with an emphasis on areas of agreement and disagreement. Ophthalmic artery chemosurgery and intravitreous chemotherapy have completely replaced external beam radiotherapy, reduced the use of systemic chemotherapy, and diminished enucleations by 90% without evidence of compromising patient survival. PMID- 26378745 TI - Experimental and Theoretical Evaluation of the Ethynyl Moiety as a Halogen Bioisostere. AB - Bioisosteric replacements are widely used in medicinal chemistry to improve physicochemical and ADME properties of molecules while retaining or improving affinity. Here, using the p53 cancer mutant Y220C as a test case, we investigate both computationally and experimentally whether an ethynyl moiety is a suitable bioisostere to replace iodine in ligands that form halogen bonds with the protein backbone. This bioisosteric transformation is synthetically feasible via Sonogashira cross-coupling. In our test case of a particularly strong halogen bond, replacement of the iodine with an ethynyl group resulted in a 13-fold affinity loss. High-resolution crystal structures of the two analogues in complex with the p53-Y220C mutant enabled us to correlate the different affinities with particular features of the binding site and subtle changes in ligand binding mode. In addition, using QM calculations and analyzing the PDB, we provide general guidelines for identifying cases where such a transformation is likely to improve ligand recognition. PMID- 26378748 TI - Tuning Nickel with Lewis Acidic Group 13 Metalloligands for Catalytic Olefin Hydrogenation. AB - A series of bimetallic complexes pairing zero-valent nickel with group 13 M(III) ions is reported. Stronger Ni->M(III) dative bonds that render Ni more electron deficient are seen for larger ions (In > Ga > Al). The larger Ga and In ions stabilize rare, nonclassical Ni-H2 adducts that catalyze olefin hydrogenation. In contrast, neither the Ni-Al complex nor a single nickel center enables H2 binding or olefin hydrogenation. By comparison of the structures, redox properties, and catalytic activities of the Ni-M series, the electronic and steric effects of the supporting metal ion are elucidated. PMID- 26378749 TI - Some ethical implications of "adaptive" trials. AB - Adaptive trials are a new type of sequential trial, as yet not very widespread, in which each step can be modified on the basis of findings from the preceding step. In other words, the data accumulated during the study are used to modify the trial design. The potential of this type of trial is highly promising, especially for the development of therapies for rare diseases. The planning, conduct and management of data from adaptive trials are extremely complex processes and call for highly specialised skills. Without going into the merits of the experimental protocols, the aim of this article is to point out some ethical aspects that call for caution, as well as the need for ethics committees to be aware of the challenges posed by these trials. PMID- 26378750 TI - [Sulphureous mud-bath therapy and changes in blood pressure: observational investigation]. AB - BACKGROUND AND OBJECTIVE: The chronic arthropathies currently appear to be a major cause of disability with a negative impact on quality of life and health care spending. The mud-bath therapy is a spa treatment that induces benefic effects in chronic rheumatic diseases. It has long been debated on the assumption that the mud-bath spa therapy could have adverse cardiovascular effects which often induce caution and even a contraindication to the use of this treatment in chronic arthropathies associated with cardiovascular alterations such as hypertension. The aim of this observational study was to investigate, in arthrorheumatic subjects, the effects of sulphureous mud-bath cycle on blood pressure and the possible appearance of adverse drug reaction. PATIENTS AND METHODS: 169 patients, with age range 42-86 years, suffering by chronic arthropathies were treated with sulphureous mud-bath therapy for 2 weeks. According to the arterial pressure values, measured before the spa treatment, the patients considered were divided in three groups: with normal blood pressure (NOR group); with high blood pressure, after, the latter group was divided in IPET (patients in treatment with antihypertensive drugs) and IPENT (patients not in antihypertensive therapy). The arterial pressure values, maximum and minimum, expressed in mmHg, were detected in the first (T1) - sixth (T6) and twelfth (T12) day of spa treatment. The media arterial pressure values collected before and after T1, before and after T6, before and after T12 , before T1 and after T12 were compared. The data, presented as mean+/-SD, were compared with the paired Student t test. A p value <=0.05 was considered significant. RESULTS: The comparison between the mean values detected in pre and post T1, pre and post T6, pre and post T12 have showed that sulphureous mud-bath therapy induced a significant (p<0.05) reduction of arterial blood pressure values in patients suffering of chronic arthropathies with high blood pressure in antihypertensive therapy or not (IPET and IPENT groups); while in patients with normal blood pressure (NOR group) were observed modest reduction at the limit of statistical significance. Similarly, the comparison between the data detected at the end of sulphureous mud-bath therapy (post-T12) vs baseline (pre-T1) have demonstrated: in IPET and IPENT groups a significant (p<0,01) decrease of arterial blood pressure values; in NOR group very small decrease, this reduction is significant (p<0.05) only for maximum arterial pressure value. Were not observed adverse drug reaction. CONCLUSIONS: The results of our study, in according with the few data in the literature, evidenced that is possible include the sulphureous mud-bath therapy in interdisciplinary therapeutic p rotocol of patients suffering of chronic arthropathies and arterial hypertension. PMID- 26378751 TI - Intracameral epinephrine without the addition of intracameral lidocaine in the management of tamsulosin associated intraoperative floppy iris syndrome. AB - OBJECTIVE: Intracameral mydriatics using epinephrine associated with lidocaine have been reported as efficacious in reducing intraoperative floppy iris syndrome (IFIS) complications during cataract surgery. The aim of this study was to verify the efficacy of intracameral epinephrine without intracameral lidocaine as prophylaxis against IFIS in patients on tamsulosin. MATERIALS AND METHODS: This was a retrospective study on the results of cataract surgery in 18 patients on therapy with tamsulosin. Patients had undergone routine phacoemulsification in one eye. Successively, they underwent phacoemulsifcation in the fellow eye using non preserved intracameral epinephrine 1:4000 diluted with BSS. Intraoperative complications during cataract surgery had been documented and IFIS was graded based on iris billowing, miosis or iris prolapse. Follow-up was 3 months. RESULTS: Thirty-six eyes of 18 patients were included in the evaluation. The incidence of IFIS was significantly higher in the eyes where routine phacoemulsificaton had been performed (100%) with respect to eyes where phacoemulsification was carried out using intracameral epinephrine (33%) (Chi Square test =15.12, p<0.001). In routine phacoemulsification 16 eyes showed iris billowing, 14 eyes had some extent of miosis and 14 eyes had tendency to iris prolapse. In phacoemulsification with the use of intracameral epinephrine 5 eyes showed iris billowing, 4 eyes presented some extent of miosis and 2 eyes had tendency to iris prolapse. There were no serious intraoperative complications. CONCLUSIONS: Intracameral epinephrine without the addition of lidocaine was efficacious in the management of IFIS in patients on tamsulosin. PMID- 26378752 TI - [Rubber band ligation in treatment of hemorrhoids: our experience]. AB - OBJECTIVES: Hemorrhoids are a very common condition. The treatment depends upon persistence and severity of symptoms. For hemorrhoids of II and III grade the rubber band ligation may be therapeutic. Our aim is to report the outcomes of rubber band ligation of hemorrhoids, with a follow up of 6 months. MATERIALS AND METHODS: A total of 50 patients underwent rubber band ligation for symptomatic hemorrhoids (grade II and III) without prolapse, between June 2012 and June 2014. All patients underwent plug test to rule out presence of rectal mucosal prolapse and were classified according to PATE classification (1). Each hemorrhoid was ligated with one rubber band through a ligator. All patients were evaluated immediately at the end of the procedure, after ten days and six months after the treatment. Patient's demographic and operative data were collected and analyzed. RESULTS: The mean patients age was 47.6+/-12.3 years (range 24-72). All procedures were performed without complications. Before rubber band ligation, 42 patients had rectal bleeding, 38 had perineal discomfort and 27 had itching. Ten days after the treatment, 12 patients presented self-limited rectal bleeding, but 10 of these had more hemorrhoids and underwent a second rubber band ligation. No patients complained perineal discomfort, and 8 patients had itching; 78% and 16% of patients respectively, experienced feeling of a foreign body inside the canal anal and anal pain. After 6 months, only 13 patients were occasionally symptomatic: 4 patients had rectal bleeding, 2 had perineal discomfort and 4 had itching. Three more patients presented both perineal discomfort and hitching. None had the feeling of a foreign body in anal canal or anal pain. CONCLUSIONS: Rubber band ligation is an efficacious, cost-effective and simple treatment for the second and third degree hemorrhoids without rectal mucosal prolapsed. In our hands, no severe complications developed and minor complications could be handled with ease. PMID- 26378753 TI - Information to be given to patients: a UK judgment marks a turning point. AB - A recent judgment by the Supreme Court of the United Kingdom marks a turning point in the way doctors should inform patients of the risks associated with clinical treatment. The Courts previously based their judgments on the so-called "Bolam test", according to which a physician's conduct would be considered acceptable if it would be supported by a responsible body of medical opinion. The new ruling overturns this approach: doctors should no longer ask themselves what is their colleagues' prevailing stance and conform to it, but should instead assess the circumstances from the point of view of the particular patient in each case. PMID- 26378754 TI - Ethical reflections of gender equality and equity in adolescence medicine. AB - Gender differences, in both clinical and research environment, exist also in a particular category of patients, adolescents, who constitute a vulnerable group with respect to healthcare decisions. In clinical context, the main ethical issues that may be identified within gender medicine for adolescent patients are related to the information given to the patient and its parents, the adolescent's capacity of understanding considering his/her maturity, vulnerability and autonomy, the consent to medical treatment in relation to the different possible approaches to their different efficacy and possible side effects. Also, with regard to the research context, ethical issues may arise from the participation of female minors in clinical trials. Ethical concerns may also arise in the field of resource allocation in health policies, such as the equitable distribution and access to resources, considering the young age of the subjects involved. A bioethical reflection, which takes into account not only the differences biologically and epidemiologically relevant, but also the main determinants of health in adolescence, might find a role in structured education for diversity and gender equity. Given the magnitude of the problem, to encourage the pursuit of gender equity in health and, in some situations, also to promote the full recognition of the right to health of women are some of the most effective and direct ways to reduce inequalities and to ensure a rational and efficient use of available resources, including through a bioethical reflection on the topic. The Authors show the necessity to differentiate the various aspects of gender differences in adolescence medicine, providing arguments in support of the fact that interventions for health prevention and promotion should be modulated in relation to the gender of the recipients, emphasizing the most important aspects for each group of individuals. This approach could implement personalized medicine, even and especially considering gender differences, benefiting from the contribution that a bioethical reflection can provide. PMID- 26378755 TI - Ectopic prolactinoma in the clivus: a case report. AB - We report the case of an ectopic pituitary adenoma in a 65-year-old man with an empty sella who initially presented with right ptosis and eyelid edema and headache. Neuroimaging studies revealed a large tumoral process at the height of the clivus, with partial destruction of surrounding bone structure. He underwent transphenoidal surgery and histopathologic examination, including immunohistochemical studies, revealed a prolactin-producing pituitary adenoma. A careful review of the literature was done. PMID- 26378756 TI - [Swimming, physical activity and health: a historical perspective]. AB - Swimming, which is the coordinated and harmonic movement of the human body inside a liquid medium by means of the combined action of the superior and inferior limbs, is a physical activity which is diffused throughout the whole world and it is practiced by healthy and non-healthy subjects. Swimming is one of the physical activities with less contraindications and, with limited exceptions, can be suggested to individuals of both sexes and of every age range, including the most advanced. Swimming requires energy both for the floating process and for the anterograde progression, with a different and variable osteo-arthro-muscular involvement according to the different styles. The energetic requirement is about four times that for running, with an overall efficiency inferior to 10%; the energetic cost of swimming in the female subject is approximately two thirds of that in the male subject. The moderate aerobic training typical of swimming is useful for diabetic and hypertensive individuals, for people with painful conditions of rachis, as also for obese and orthopaedic patients. Motor activity inside the water reduces the risk of muscular-tendinous lesions and, without loading the joints in excess, requires the harmonic activation of the whole human musculature. Swimming is an activity requiring multiple abilities, ranging from a sense of equilibrium to that of rhythm, from reaction speed to velocity, from joint mobility to resistance. The structured interest for swimming in the perspective of human health from the beginning of civilization, as described in this contribution, underlines the relevance attributed to this activity in the course of human history. PMID- 26378757 TI - Axis II disorders, body image and childhood abuse in bariatric surgery candidates. AB - BACKGROUND AND AIMS: Psychiatric disorders are common in obese patients and they are often considered contraindications for bariatric surgery. In this patients Axis I profile has been widely investigated, while only few studies on Axis II profile are reported. Aim of the study was to examine the prevalence of Axis II psychopathology, to describe the typical body image and to evaluate the prevalence of childhood abuse in bariatric surgery candidates. MATERIALS AND METHODS: A total of 102 consecutive obese patients (77 females) were evaluated by the Structured Clinical Interview for DSM IV which assessed Axis I Disorders. After the exclusion of Axis I Disorders, 50 patients (36 females, BMI: 44.68 +/- 9.48 Kg/m2, age: 44.5 +/- 11.7 years) were enrolled. All 50 patients received a psychiatric assessment including the Structured Clinical Interview for DSM-IV Axis II Disorders (SCID-II); the Body Uneasiness Test, part a (BUT-A), which assesses body image disorders; the Childhood Trauma Questionnaire (CTQ) as a screening test of childhood maltreatment histories. RESULTS: Nineteen patients (38%) were affected by Axis II disorders. Cluster C disorders, including avoidant, dependent and obsessive-compulsive personality disorders, represented the most common diagnosis (24%). Moreover, 34 patients (68%) showed body image disorders (BID), with a GSI score >=1.2 and 24 (48%) referred an abuse during childhood. Patients with Axis II disorder or a body image uneasiness or a history of maltreatment during childhood, showed higher BMI in adulthood. CONCLUSIONS: Psychiatric comorbidities in obese patients were not only represented by depression or anxiety (Axis I disorders), but also by personality disorders (Axis II), body image disorders and childhood abuse. The identification of these conditions could improve outcomes of bariatric surgery and represent an indication for a most important psychiatric support before, during and after surgery. PMID- 26378758 TI - Corneal iontophoresis and cross linking: a preliminary report of our experience. AB - PURPOSE: To evaluate the effect induced by UVA radiation with corneal iontophoresis and cross-linking. MATERIALS AND METHODS: From February 2013 to August 2014 we saw 15 eyes of 15 patients, age range 19-38 years (10 women and 5 men) keratoconus stage 1-2. Vision evaluation was carried out with ETDRS scale and Topography and Pachymetry. To evaluate line of demarcation with the confocal microscope and corneal optical coherence tomography (OCT) and the pain with the Faces Pain Scale. RESULTS: At 6 months there was a stabilization of vision and topography, with a slight improvement at 1 year of vision of 1 line and of the Km of 0.5 diopters. The in vivo microscopic examination with the confocal microscope showed that the line of demarcation was not particularly evident, it was irregular and when present was more evident at 150-200 u depth, there was a keratinocyte activation in the anterior stroma with slight oedema. There were also superficial epithelial alterations present and only slight involvement of the subepithelial nervous plexus, there were no alterations of the endothelium. The Faces Pain Scale the pain score was 2+/-1. We have to stress the usefulness of Corneal optical coherence tomography (OCT) also pre and post iontophoretic treatment. CONCLUSIONS: Further, larger studies and longer follow-ups are needed, recent studies have shown the absorption of riboflavin with iontophoresis is 50% with respect to the classic technique, the percentage of riboflavin in the anterior 2/3 of the corneal stroma would be, however, efficacious to provide good results. PMID- 26378759 TI - Does neuromuscular taping influence hand kinesiology? A pilot study on Down's Syndrome. AB - PURPOSE: This paper is a first attempt analysis of hand and upper limb proprioception coordination induced by NeuroMuscular Taping (NMT): application in a group of 5 participants with Down syndrome. MATERIALS AND METHODS: The participants underwent a drawing test with motion capture system acquisition before and after NMT application. Specific and descriptive parameters were computed and analysed in order to quantify the differences. RESULTS: Results showed statistical differences between pre and post treatment sessions: the 5 participants with Down syndrome evidenced more reliance on proprioceptive signals in the post treatment session during the execution of the specific writing tasks. CONCLUSIONS: Based on the hypothesis that modifications in proprioception should alter motor pathway mapping of the motor cortex, Neuromuscular taping may play a role in the treatment of dysgraphia and improving hand coordination following CNS impairment, even though a small treatment group was chosen for this pilot study the results lead to further discussions concerning the role of different afferent signals in a pathological context. PMID- 26378760 TI - The Body Worlds Exhibits and Juvenile Understandings of Death: Do We Educate Children to Science or to Voyeurism? AB - Gunther von Hagens' development of plastination as a method for preserving human remains has enabled his public display of skinless, dissected bodies in a series of popular international exhibitions entitled Body Worlds. These spectacular displays claim to be educative, democratizing the study of anatomy and liberating it from the traditional confines of professional medical study. However, Body Worlds has raised various ethical objections to its commercial purpose, sourcing of some bodies and arrangement of bodies in poses or dissections that some viewers find offensive. Here we consider a different, often overlooked ethical conundrum raised by these exhibitions: the likelihood that the viewing of plastinates posed in 'frozen motion' is ill-suited to the psychological development of young children (5-10 years old) whose understanding of death is still in formation. Often young children mistake corpses for models, even for living beings if they are posed in arrested motion. The educative value of Body Worlds for younger viewers is questionable and the display may even interfere with their understanding of death. If the exhibition of human remains can be justified where their authenticity can be made known to viewers and the remains invested by them with sympathetic emotional meaning, it may be pointless if not unethical to show quasi-lifelike posed plastinates to young children in lieu of replica models. PMID- 26378761 TI - Cutaneous manifestations and gastrointestinal disorders: Report of two emblematic cases. AB - Gastrointestinal (GI) diseases, such as inflammatory bowel diseases (IBD), can manifest themselves with intestinal and extra-intestinal symptoms. Among the latter, cutaneous manifestations, such as pyoderma gangraenosum (PG) and metastatic Crohn's disease (MCD), represent a possible onset of IBD, with or without simultaneous bowel alterations. In such cases, intestinal and skin lesions are supported by the same immune-mediated mechanism. We hereby report two cases of patients with skin manifestations together with signs and symptoms suggestive of IBD. IBD and some skin lesions arise from the same immune-mediated mechanism. A multidisciplinary approach to these immune-mediated diseases is needed for an early and correct diagnosis, which in turn may lead to the use of the right drug avoiding useless treatment. PMID- 26378762 TI - [A case report of eccrine porocarcinoma]. AB - Eccrine porocarcinoma (EPC) is a rare malignant skin appendage tumour deriving from the intraepithelial ductal parts of the sweat glands. First described by Pinkus e Mehregan nel 1963 as an epidermotropic eccrine carcinoma, it is rarely reported in medical literature and represents 0.005-0.01% of all skin tumors. We report a case of a 88-year-old Caucasian female presented to our Clinic with an asymptomatic, red-brown , irregularly shaped firm nodule on the left thigh aroused 15 years earlier. The lesion has been excised and histopathological examination showed an "eccrine porocarcinoma aroused on eccrine poroma". Review of the literature on this rare condition and possible therapeutic strategies are also discussed. PMID- 26378763 TI - [Ethics in clinical practice and in health care]. AB - The clinical ethics is the identification, analysis and solution of moral problems that can arise during the care of a patient. Given that when dealing with ethical issues in health care some risks will be encountered (talking about ethics in general, or as a problem overlapped with others in this area, or by delegation to legislative determinations) in the text certain important aspects of the topic are examined. First of all ethics as human quality of the relationship between people for the common good, especially in health services where there are serious problems like the life and the health. It is also necessary a "humanizing relationship" between those who work in these services in order to achieve quality and efficiency in this business. It is important a proper training of health professionals, especially doctors, so that they can identify the real needs and means of intervention. It is also important that scientific research must respect fundamental ethical assumptions. In conclusion, ethics in health care is not a simple matter of "cookbook" rules, but involves the responsibility and consciousness of individual operators. PMID- 26378764 TI - [From algae to "functional foods"]. AB - In the recent years, a growing interest for nutraceutical algae (tablets, capsules, drops) has been developed, due to their effective health benefits, as a potential alternative to the classic drugs. This review explores the use of cyanobacterium Spirulina, the microalgae Chlorella, Dunaliella, Haematococcus, and the macroalgae Klamath, Ascophyllum, Lithothamnion, Chondrus, Hundaria, Glacilaria, Laminaria, Asparagopsis, Eisenia, Sargassum as nutraceuticals and dietary supplements, in terms of production, nutritional components and evidence based health benefits. Thus, our specific goals are: 1) Overview of the algae species currently used in nutraceuticals; 2) Description of their characteristics, action mechanisms, and possible side effects; 3) Perspective of specific algae clinical investigations development. PMID- 26378765 TI - Palladium-Catalyzed Ring Expansion of Spirocyclopropanes to Form Caprolactams and Azepanes. AB - A palladium(0)-catalyzed rearrangement of piperidones and piperidines bearing a spirocyclopropane ring was developed. The ring expansion reaction led to a variety of functionalized caprolactam and azepane products in good to excellent yields. Experimental and computational mechanistic studies revealed an initial oxidative addition of the distal carbon-carbon bond of a cyclopropane ring to the palladium(0) catalyst and the relief of ring strain as a driving force for product formation. PMID- 26378766 TI - Preventive Role of Tetraspanin CD9 in Systemic Inflammation of Chronic Obstructive Pulmonary Disease. AB - Chronic obstructive pulmonary disease (COPD) is frequently associated with extrapulmonary complications, including cardiovascular disease, diabetes, and osteoporosis. Persistent, low-grade, systemic inflammation underlies these comorbid disorders. Tetraspanins, which have a characteristic structure spanning the membrane four times, facilitate lateral organization of molecular complexes and thereby form tetraspanin-enriched microdomains that are distinct from lipid rafts. Recent basic research has suggested a preventive role of tetraspanin CD9 in COPD. CD9-enriched microdomains negatively regulate LPS-induced receptor formation by preventing CD14 from accumulating into the rafts, and decreased CD9 in macrophages enhances inflammation in mice. Mice doubly deficient in CD9 and a related tetraspanin, CD81, show pulmonary emphysema, weight loss, and osteopenia, a phenotype akin to human COPD. A therapeutic approach to up-regulating CD9 in macrophages might improve the clinical course of patients with COPD with comorbidities. PMID- 26378767 TI - Effect of activated carbon or biochars on toxicity of different soils contaminated by mixture of native polycyclic aromatic hydrocarbons and heavy metals. AB - Activated carbon (AC), biochar from wheat straw (BCS), and biochar from willow (BCW) were added to the soils sampled from areas of strong anthropogenic influence at doses of 0.5%, 1%, 2.5%, or 5% (w/w) and incubated for 2 mo. At the end of this period, the toxicity of the soils was measured. The effect of AC and biochars on the toxicity of the soils varied based on soil, type of amendment, dose, and test organism. For most of the parameters tested, the highest effectiveness of AC in terms of reduction of toxicity was observed in soil POPI (from bitumen processing plant area). In the case of the remaining soils, after the addition of AC varied results were observed, in which a reduction or an increase of toxicity, relative to the control soil, occurred. As in the case of AC, biochars also caused a significant reduction of phytotoxicity of soil POPI. In soils KB (from coking plant area, industrial waste deposit) and KOK (from coking plant area, coking battery), the reduction or increase of toxicity depended on biochar dose. Compared with the biochars, the effectiveness of AC in the reduction of toxicity depended also on soil, type of amendment, dose, and test organism. Generally, the AC was more effective than biochars in relation to mortality and reproduction of Folsomia candida (in all soils) and for reduction of luminescence inhibition of Vibrio fischeri (in POPI soil). PMID- 26378768 TI - Fall-related injuries among Canadian seniors, 2005-2013: an analysis of the Canadian Community Health Survey. AB - INTRODUCTION: We describe the epidemiology and trends of fall-related injuries among Canadian seniors aged 65 years and older by sex and age, as well as the circumstances and consequences of their injuries. METHODS: We analyzed nationally representative data from the 2005, 2009/2010 and 2013 samples of the Canadian Community Health Survey to calculate the number and rates of fall-related injuries for each survey year. Where possible, we combined data from two or more samples to estimate the proportion of fall-related injuries by type of injury, part of body injured, type of activity and type of treatment. RESULTS: The rate of fall-related injuries among seniors increased from 49.4 to 58.8 per 1000 population between 2005 and 2013, during which the number of fall-related injuries increased by 54% overall. Women had consistently higher rates than men across all survey years, while rates increased with advancing age. The upward trend in fall-related injury rates was more prominent among women and younger age groups. The most common type of injury was broken or fractured bones (37%), and the shoulder or upper arm (16%) was the most commonly injured body part. Many fall-related injuries occurred while walking on a surface other than snow or ice (45%). Over 70% of seniors seeking treatment for their injuries visited a hospital emergency department. CONCLUSION: Given the increase in both the number and rates of fall-related injuries over time, there is a need to continue monitoring trends and injury patterns associated with falls. PMID- 26378770 TI - Report Summary--Rio Political Declaration on Social Determinants of Health: A Snapshot of Canadian Actions 2015. AB - In 2012, Canada and other United Nations (UN) Member States endorsed the "Rio Political Declaration on Social Determinants of Health" (Rio Declaration), a non binding pledge which calls on World Health Organization (WHO) Member States to improve/influence the working and living conditions that affect health and well being. The Rio Declaration sets out actions to address health inequities in five themes: to adopt better governance for health and development; to promote participation in policy making and implementation; to further reorient the health sector towards reducing health inequities; to strengthen global governance and collaboration; and to monitor and increase accountability. In 2013, following the endorsement of the Rio Declaration, the Government of Canada released a report to begin to document Canadian actions related to its five themes. Building on this first report, and in anticipation of WHO reporting on Member State implementation of the Rio Declaration at the May 2015 World Health Assembly, the Government of Canada developed the report, Rio Political Declaration on Social Determinants of Health: A Snapshot of Canadian Actions 2015, which showcases Canada's recent actions since 2013 contributing to the advancement of the five Rio Declaration themes. The report provides a current picture of the diverse spectrum of activities undertaken across levels of government and sectors to advance health equity and address social determinants of health in Canada, and intends to stimulate global and domestic exchange and uptake of promising practices to advance health equity. PMID- 26378769 TI - Evidence Brief--Trends and projections of obesity among Canadians. AB - The prevalence of obesity, defined as body mass index (BMI) of 30 kg/m2 or higher for adults and as 2 standard deviations above the World Health Organization growth standard mean for children, has increased in many parts of the world. Obese adults are at an increased risk of certain chronic conditions, including hypertension, type 2 diabetes, cardiovascular diseases and some cancers, and of premature death. Obese children have increased cardiometabolic risk, including dyslipidemia, insulin resistance and elevated blood pressure. Excess childhood body weight that continues into adulthood can affect quality of life, educational attainment and earnings over the lifecourse. The Public Health Agency of Canada has projected an annual direct health care cost (including physician, hospitalization and medication costs) of those categorized as obese in Canada in constant 2001 Canadian dollars. Calculated as $7.0 billion in 2011, this annual direct health care cost is projected to rise to $8.8 billion by 2021, based on simulated average direct health care costs, which are higher among the obese ($2,283) than the overweight ($1,726), the underweight ($1,298) and those at normal weight ($1,284). Canadian estimates from 2006 and 2008 that used different methodologies place the annual economic burden (direct and indirect costs) of obesity between $4.6 billion and $7.1 billion. The purpose of this evidence brief is to show current Canadian obesity prevalence rates and estimates for the future using objectively measured height and weight to calculate BMI. The use of objectively measured height and weight to derive BMI is strongly recommended, especially for children and adolescents, as self- or proxy-reported height and weight tend to underestimate actual weight and consequently BMI and obesity prevalence. PMID- 26378771 TI - Photon Upconversion Through Tb(3+) -Mediated Interfacial Energy Transfer. AB - A strategy of interfacial energy transfer upconversion is demonstrated through the use of a terbium (Tb(3+) ) dopant as energy donor or energy migrator in core shell-structured nanocrystals. This mechanistic investigation presents a new pathway for photon upconversion, and, more importantly, contributes to the better control of energy transfer at the nanometer length scale. PMID- 26378772 TI - Prediction of Incident Major Osteoporotic and Hip Fractures by Trabecular Bone Score (TBS) and Prevalent Radiographic Vertebral Fracture in Older Men. AB - Trabecular bone score (TBS) has been shown to predict major osteoporotic (clinical vertebral, hip, humerus, and wrist) and hip fractures in postmenopausal women and older men, but the association of TBS with these incident fractures in men independent of prevalent radiographic vertebral fracture is unknown. TBS was estimated on anteroposterior (AP) spine dual-energy X-ray absorptiometry (DXA) scans obtained at the baseline visit for 5979 men aged >=65 years enrolled in the Osteoporotic Fractures in Men (MrOS) Study and its association with incident major osteoporotic and hip fractures estimated with proportional hazards models. Model discrimination was tested with Harrell's C-statistic and with a categorical net reclassification improvement index, using 10-year risk cutpoints of 20% for major osteoporotic and 3% for hip fractures. For each standard deviation decrease in TBS, there were hazard ratios of 1.27 (95% confidence interval [CI] 1.17 to 1.39) for major osteoporotic fracture, and 1.20 (95% CI 1.05 to 1.39) for hip fracture, adjusted for FRAX with bone mineral density (BMD) 10-year fracture risks and prevalent radiographic vertebral fracture. In the same model, those with prevalent radiographic vertebral fracture compared with those without prevalent radiographic vertebral fracture had hazard ratios of 1.92 (95% CI 1.49 to 2.48) for major osteoporotic fracture and 1.86 (95% CI 1.26 to 2.74) for hip fracture. There were improvements of 3.3%, 5.2%, and 6.2%, respectively, of classification of major osteoporotic fracture cases when TBS, prevalent radiographic vertebral fracture status, or both were added to FRAX with BMD and age, with minimal loss of correct classification of non-cases. Neither TBS nor prevalent radiographic vertebral fracture improved discrimination of hip fracture cases or non-cases. In conclusion, TBS and prevalent radiographic vertebral fracture are associated with incident major osteoporotic fractures in older men independent of each other and FRAX 10-year fracture risks, and these data support their use in conjunction with FRAX for fracture risk assessment in older men. PMID- 26378773 TI - Orthopedic implant infections: Incompetence of Staphylococcus epidermidis, Staphylococcus lugdunensis, and Enterococcus faecalis to invade osteoblasts. AB - Septic failure is still the major complication of prosthetic implants. Entering host cells, bacteria hide from host immune defenses, shelter from extracellular antibiotics, and cause chronic infection. Staphylococcus aureus, the leading etiologic agent of orthopedic implant infections, is able to enter bone cells and induce osteoblast apoptosis, osteoclast recruitment, and highly destructive osteomyelitis. Staphylococcus epidermidis, Staphylococcus lugdunensis, and Enterococcus faecalis are opportunistic pathogens causative of implant-related infections. This study investigated the ability to internalize into osteoblastic MG63 cells of 22 S. epidermidis, 9 S. lugdunensis, and 21 E. faecalis clinical isolates from orthopedic implant infections. Isolates were categorized in clusters by ribotyping. Internalization assay was carried out by means of a microtiter plate-based method. S. epidermidis, S. lugdunensis, and E. faecalis strains turned out incompetent to enter osteoblasts, exhibiting negligible internalization into MG63 cells, nearly three orders of magnitude lower than that of S. aureus. Osteoblast invasion does not appear as a pathogenetic mechanism utilized by S. epidermidis, S. lugdunensis, or E. faecalis for infecting orthopedic implants. Moreover, it can be inferred that intracellularly active antimicrobials should not be necessary against implant infections caused by the three bacterial species. Finally, implications with the uptake of biomaterial microparticles by nonphagocytic cells are enlightened. (c) 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 788-801, 2016. PMID- 26378774 TI - Hospitalizations During Systemic Therapy for Metastatic Lung Cancer: A Systematic Review of Real World vs Clinical Trial Outcomes. AB - IMPORTANCE: Understanding the risk of hospitalization due to treatment-related toxic effects is essential for patients, their clinicians, and health systems. Unplanned hospitalizations represent potential gaps in patient care; definition of these gaps allows characterization and identification of areas for quality improvement. OBJECTIVE: To compare the rates of hospitalization in patients with metastatic non-small-cell lung cancer (mNSCLC) receiving chemotherapy in the "real world" vs clinical trial settings and to identify factors associated with hospitalization. EVIDENCE REVIEW: A systematic review of Medline and EMBASE was conducted for records dating from database inception (1946 and 1974, respectively) through December 2014 to identify articles reporting rates of hospitalization during chemotherapy in patients with cancer. Both observational studies and clinical trials were eligible. This report focuses on patients with mNSCLC receiving chemotherapy because data were available for this clinical scenario in both the clinical trial and observational setting, allowing comparison. Summary statistics were used to describe results, and the chi2 test was used to compare hospitalization rates. FINDINGS: Of the 74 articles reporting hospitalization rates during chemotherapy, 10 studies, all published after 2004, examined chemotherapy in mNSCLC, 5 randomized clinical trials (3962 patients) and 5 observational studies (8624 patients). Chemotherapy regimens included doublet therapy, single-agent therapy, or chemotherapy type unspecified. The real world cohort was older (71 vs 63 years). All real world studies reported on comorbidities, while clinical trials reported performance status. The aggregate hospitalization rate among real world patients was significantly higher than among trial patients (51% vs 16%) (odds ratio, 7.7; 95% CI, 7.0-8.4; P < .001). Performance status and type of chemotherapy were associated with hospitalization during chemotherapy in clinical trials, while type of chemotherapy was a risk factor in observational studies. CONCLUSIONS AND RELEVANCE: Clinical trials in mNSCLC consistently report significantly lower rates of hospitalization than reports of real world cohorts of patients undergoing similar therapies. However, very few clinical trials report hospitalization information. PMID- 26378775 TI - [Establishment of a Neonatal ECMO Programme on the Basis of a Special Training Programme--A 6-year Analysis]. AB - BACKGROUND: Internationally the need for neonatal ECMO is decreasing and the Extracorporeal Life Support Organization (ELSO) recommends that centres providing neonatal ECMO should treat at least 6 children per year. METHOD: After a one-year training programme and preparation of the clinical application, neonatal ECMO was established and subsequently 41 infants [median age 1 day (1-172 days), median weight 3.25 kg (1.27-5.79 kg)] with severe respiratory failure have been treated within a 6-year period (fall 2008-fall 2014). For rescue therapy we provide inhaled nitric oxide, high-frequency oscillation and other differentiated ventilator strategies. Parallel to the clinical use of ECMO all employees have been trained in a special programme at 3-monthly intervals. RESULTS: By establishing an elaborate training programme and concentrating the treatment of critically ill newborns in one centre, the expertise of both running and preventing of neonatal ECMO due to pulmonary failure can be achieved. The diagnoses correlate to those of other centres which perform neonatal ECMO. 13 infants needed ECMO. The resulting overall survival rate was 11/12 (91.7%) infants treated with ECMO with a curative approach. All patients could be weaned from ECMO. CONCLUSION: In the context of a specialised university hospital with all treatment options for critically ill newborns and with the establishment of a specialised training programme, neonatal ECMO for pulmonary failure can achieve equally good results in comparison to those of national and international ECMO centres. PMID- 26378776 TI - [German Version of the Childbirth Self-Efficacy Inventory and its Short Form]. AB - BACKGROUND: The Childbirth Self-Efficacy Inventory (CBSEI) is an instrument that measures women's perceived self-efficacy towards labour. It is used in 9 countries, a 32-item short form (CBSEI-C32) in 4 countries. German versions of the CBSEI and the CBSEI-C32 have not been developed thus far. METHODS: A forward backward translation was performed, followed by administration of both instruments to a sample of 155 participants of antenatal classes. Pregnant women answered questions regarding their medical history and user-friendliness of the instruments. 80 respondents completed the CBSEI, 75 the CBSEI-C32. Reliability via Cronbach alpha was calculated for the 4 subscales of the CBSEI and the 2 subscales of the short form. Validity was only assessed for the 2 scales of the CBSEI-C32 because all women (n=155) completed this instrument. RESULTS: 2 Cronbach alpha values were greater than 0.74 (adequate), the others greater than 0.80 (good). Most of the factors of the CBSEI-C32 (75%) were above >=0.5. Calculation of the item-to-total-correlations revealed that the exclusion of 3 items might be indicated for the German version. The short form showed a significant association between level of education and perceived self-efficacy (p=0.01). RESULTS in the area of user-friendliness were more encouraging for the CBSEI-C32 than for the CBSEI. CONCLUSION: The German version of the CBSEI is a useful instrument which may improve advice and counselling during prenatal care in Germany. PMID- 26378777 TI - Industry perspectives on biomarker qualification. AB - Biomarkers have the potential to expedite drug development, increase patient safety, and optimize clinical response. Yet few have achieved regulatory qualification. A survey was conducted to clarify industry's perspective on biomarker qualification and identify the most promising biomarkers for drug development. The results across toxicities/clinical areas highlight challenges in regulatory qualification, although early prioritization and alignment on an evidentiary standard framework are key factors in facilitating biomarker development and qualification. PMID- 26378778 TI - Acceptance of intradermal inactivated influenza vaccines among hospital staff following 2 seasonal vaccination campaigns. AB - After a Canadian hospital's official influenza vaccination campaign concluded in the 2011-2012 and 2012-2013 influenza seasons, study nurses provided additional vaccination mobile cart hours and the added choice of an intradermal injection. An additional 2.1% of staff in the first and 1.4% in the second season were vaccinated during the study with 90-99% preferring the intradermal injection or having no preference. All 13 staff who attempted self-injection with the intradermal vaccine in 2012-2013 were successful on their first attempt. Offering alternatives to intramuscular vaccines may increase rates of vaccination. PMID- 26378779 TI - Expression and Function of mARC: Roles in Lipogenesis and Metabolic Activation of Ximelagatran. AB - Recently two novel enzymes were identified in the outer mitochondrial membrane, mARC1 and mARC2. These molybdenum containing enzymes can reduce a variety of N hydroxylated compounds, such as N-hydroxy-guanidines and sulfohydroxamic acids, as well as convert nitrite into nitric oxide (NO). However, their endogenous functions remain unknown. Here we demonstrate a specific developmental pattern of expression of these enzymes. mARC1, but not mARC2, was found to be expressed in fetal human liver, whereas both, in particular mARC2, are abundant in adult liver and also expressed in omental and subcutaneous fat. Caloric diet restriction of obese patients caused a decreased expression of mARC2 in liver, similar to that seen in the livers of starved rats. Knock down of mARC2 expression by siRNA in murine adipocytes had statistically significant effect on the level of diglycerides and on the fatty acid composition of some triglycerides, concomitantly a clear trend toward the reduced formation of most of triglyceride and phospholipid species was observed. The involvement of mARC2 in the metabolism of the hepatotoxic drug ximelagatran was evaluated in hepatocytes and adipocytes. Ximelagatran was shown to cause oxidative stress and knock down of mARC2 in adipocytes prevented ximelagatran induced inhibition of mitochondrial respiration. In conclusion, our data indicate that mARC1 and mARC2 have different developmental expression profiles, and that mARC2 is involved in lipogenesis, is regulated by nutritional status and responsible for activation of ximelagatran into a mitotoxic metabolite(s). PMID- 26378780 TI - Novel Nuclear Protein Complexes of Dystrophin 71 Isoforms in Rat Cultured Hippocampal GABAergic and Glutamatergic Neurons. AB - The precise functional role of the dystrophin 71 in neurons is still elusive. Previously, we reported that dystrophin 71d and dystrophin 71f are present in nuclei from cultured neurons. In the present work, we performed a detailed analysis of the intranuclear distribution of dystrophin 71 isoforms (Dp71d and Dp71f), during the temporal course of 7-day postnatal rats hippocampal neurons culture for 1h, 2, 4, 10, 15 and 21 days in vitro (DIV). By immunofluorescence assays, we detected the highest level of nuclear expression of both dystrophin Dp71 isoforms at 10 DIV, during the temporal course of primary culture. Dp71d and Dp71f were detected mainly in bipolar GABAergic (>=60%) and multipolar Glutamatergic (<=40%) neurons, respectively. We also characterized the existence of two nuclear dystrophin-associated protein complexes (DAPC): dystrophin 71d or dystrophin 71f bound to beta-dystroglycan, alpha1-, beta-, alpha2-dystrobrevins, alpha-syntrophin, and syntrophin-associated protein nNOS (Dp71d-DAPC or Dp71f DAPC, respectively), in the hippocampal neurons. Furthermore, both complexes were localized in interchromatin granule cluster structures (nuclear speckles) of neuronal nucleoskeleton preparations. The present study evinces that each Dp71's complexes differ slightly in dystrobrevins composition. The results demonstrated that Dp71d-DAPC was mainly localized in bipolar GABAergic and Dp71f-DAPC in multipolar Glutamatergic hippocampal neurons. Taken together, our results show that dystrophin 71d, dystrophin 71f and DAP integrate protein complexes, and both complexes were associated to nuclear speckles structures. PMID- 26378781 TI - Structural and Biochemical Analysis of a Single Amino-Acid Mutant of WzzBSF That Alters Lipopolysaccharide O-Antigen Chain Length in Shigella flexneri. AB - Lipopolysaccharide (LPS), a surface polymer of Gram-negative bacteria, helps bacteria survive in different environments and acts as a virulence determinant of host infection. The O-antigen (Oag) component of LPS exhibits a modal chain length distribution that is controlled by polysaccharide co-polymerases (PCPs). The molecular basis of the regulation of Oag chain-lengths remains unclear, despite extensive mutagenesis and structural studies of PCPs from Escherichia coli and Shigella. Here, we identified a single mutation (A107P) of the Shigella flexneri WzzBSF, by a random mutagenesis approach, that causes a shortened Oag chain-length distribution in bacteria. We determined the crystal structures of the periplasmic domains of wild-type WzzBSF and the A107P mutant. Both structures form a highly similar open trimeric assembly in the crystals, and show a similar tendency to self-associate in solution. Binding studies by bio-layer interferometry reveal cooperative binding of very short (VS)-core-plus-O-antigen polysaccharide (COPS) to the periplasmic domains of both proteins, but with decreased affinity for the A107P mutant. Our studies reveal that subtle and localized structural differences in PCPs can have dramatic effects on LPS chain length distribution in bacteria, for example by altering the affinity for the substrate, which supports the role of the structure of the growing Oag polymer in this process. PMID- 26378782 TI - Genetic Ablation of the ClC-2 Cl- Channel Disrupts Mouse Gastric Parietal Cell Acid Secretion. AB - The present studies were designed to examine the effects of ClC-2 ablation on cellular morphology, parietal cell abundance, H/K ATPase expression, parietal cell ultrastructure and acid secretion using WT and ClC-2-/- mouse stomachs. Cellular histology, morphology and proteins were examined using imaging techniques, electron microscopy and western blot. The effect of histamine on the pH of gastric contents was measured. Acid secretion was also measured using methods and secretagogues previously established to give maximal acid secretion and morphological change. Compared to WT, ClC-2-/- gastric mucosal histological organization appeared disrupted, including dilation of gastric glands, shortening of the gastric gland region and disorganization of all cell layers. Parietal cell numbers and H/K ATPase expression were significantly reduced by 34% (P<0.05) and 53% (P<0.001) respectively and cytoplasmic tubulovesicles appeared markedly reduced on electron microscopic evaluation without evidence of canalicular expansion. In WT parietal cells, ClC-2 was apparent in a similar cellular location as the H/K ATPase by immunofluorescence and appeared associated with tubulovesicles by immunogold electron microscopy. Histamine-stimulated [H+] of the gastric contents was significantly (P<0.025) lower by 9.4 fold (89%) in the ClC-2-/- mouse compared to WT. Histamine/carbachol stimulated gastric acid secretion was significantly reduced (range 84-95%, P<0.005) in ClC-2-/- compared to WT, while pepsinogen secretion was unaffected. Genetic ablation of ClC-2 resulted in reduced gastric gland region, reduced parietal cell number, reduced H/K ATPase, reduced tubulovesicles and reduced stimulated acid secretion. PMID- 26378783 TI - The Impact of Sleep Restriction and Simulated Physical Firefighting Work on Acute Inflammatory Stress Responses. AB - OBJECTIVES: This study investigated the effect restricted sleep has on wildland firefighters' acute cytokine levels during 3 days and 2 nights of simulated physical wildfire suppression work. METHODS: Firefighters completed multiple days of physical firefighting work separated by either an 8-h (Control condition; n = 18) or 4-h (Sleep restriction condition; n = 17) sleep opportunity each night. Blood samples were collected 4 times a day (i.e., 06:15, 11:30, 18:15, 21:30) from which plasma cytokine levels (IL-6, IL-8, IL-1beta, TNF-alpha, IL-4, IL-10) were measured. RESULTS: The primary findings for cytokine levels revealed a fixed effect for condition that showed higher IL-8 levels among firefighters who received an 8-h sleep each night. An interaction effect demonstrated differing increases in IL-6 over successive days of work for the SR and CON conditions. Fixed effects for time indicated that IL-6 and IL-4 levels increased, while IL 1beta, TNF-alpha and IL-8 levels decreased. There were no significant effects for IL-10 observed. CONCLUSION: Findings demonstrate increased IL-8 levels among firefighters who received an 8-h sleep when compared to those who had a restricted 4-h sleep. Firefighters' IL-6 levels increased in both conditions which may indicate that a 4-h sleep restriction duration and/or period (i.e., 2 nights) was not a significant enough stressor to affect this cytokine. Considering the immunomodulatory properties of IL-6 and IL-4 that inhibit pro inflammatory cytokines, the rise in IL-6 and IL-4, independent of increases in IL 1beta and TNF-alpha, could indicate a non-damaging response to the stress of simulated physical firefighting work. However, given the link between chronically elevated cytokine levels and several diseases, further research is needed to determine if firefighters' IL-8 and IL-6 levels are elevated following repeated firefighting deployments across a fire season and over multiple fire seasons. PMID- 26378784 TI - A Gene Regulatory Program for Meiotic Prophase in the Fetal Ovary. AB - The chromosomal program of meiotic prophase, comprising events such as laying down of meiotic cohesins, synapsis between homologs, and homologous recombination, must be preceded and enabled by the regulated induction of meiotic prophase genes. This gene regulatory program is poorly understood, particularly in organisms with a segregated germline. We characterized the gene regulatory program of meiotic prophase as it occurs in the mouse fetal ovary. By profiling gene expression in the mouse fetal ovary in mutants with whole tissue and single cell techniques, we identified 104 genes expressed specifically in pre-meiotic to pachytene germ cells. We characterized the regulation of these genes by 1) retinoic acid (RA), which induces meiosis, 2) Dazl, which is required for germ cell competence to respond to RA, and 3) Stra8, a downstream target of RA required for the chromosomal program of meiotic prophase. Initial induction of practically all identified meiotic prophase genes requires Dazl. In the presence of Dazl, RA induces at least two pathways: one Stra8-independent, and one Stra8 dependent. Genes vary in their induction by Stra8, spanning fully Stra8 independent, partially Stra8-independent, and fully Stra8-dependent. Thus, Stra8 regulates the entirety of the chromosomal program but plays a more nuanced role in governing the gene expression program. We propose that Stra8-independent gene expression enables the stockpiling of selected meiotic structural proteins prior to the commencement of the chromosomal program. Unexpectedly, we discovered that Stra8 is required for prompt down-regulation of itself and Rec8. Germ cells that have expressed and down-regulated Stra8 are refractory to further Stra8 expression. Negative feedback of Stra8, and subsequent resistance to further Stra8 expression, may ensure a single, restricted pulse of Stra8 expression. Collectively, our findings reveal a gene regulatory logic by which germ cells prepare for the chromosomal program of meiotic prophase, and ensure that it is induced only once. PMID- 26378785 TI - Gliadin Induces Neutrophil Migration via Engagement of the Formyl Peptide Receptor, FPR1. AB - BACKGROUND: Gliadin, the immunogenic component within gluten and trigger of celiac disease, is known to induce the production of Interleukin-8, a potent neutrophil-activating and chemoattractant chemokine. We sought to study the involvement of neutrophils in the early immunological changes following gliadin exposure. METHODS: Utilizing immunofluorescence microscopy and flow cytometry, the redistribution of major tight junction protein, Zonula occludens (ZO)-1, and neutrophil recruitment were assessed in duodenal tissues of gliadin-gavaged C57BL/6 wild-type and Lys-GFP reporter mice, respectively. Intravital microscopy with Lys-GFP mice allowed monitoring of neutrophil recruitment in response to luminal gliadin exposure in real time. In vitro chemotaxis assays were used to study murine and human neutrophil chemotaxis to gliadin, synthetic alpha-gliadin peptides and the neutrophil chemoattractant, fMet-Leu-Phe, in the presence or absence of a specific inhibitor of the fMet-Leu-Phe receptor-1 (FPR1), cyclosporine H. An irrelevant protein, zein, served as a control. RESULTS: Redistribution of ZO-1 and an influx of CD11b+Lys6G+ cells in the lamina propria of the small intestine were observed upon oral gavage of gliadin. In vivo intravital microscopy revealed a slowing down of GFP+ cells within the vessels and influx in the mucosal tissue within 2 hours after challenge. In vitro chemotaxis assays showed that gliadin strongly induced neutrophil migration, similar to fMet-Leu-Phe. We identified thirteen synthetic gliadin peptide motifs that induced cell migration. Blocking of FPR1 completely abrogated the fMet-Leu Phe-, gliadin- and synthetic peptide-induced migration. CONCLUSIONS: Gliadin possesses neutrophil chemoattractant properties similar to the classical neutrophil chemoattractant, fMet-Leu-Phe, and likewise uses FPR1 in the process. PMID- 26378786 TI - Comparison of Different Scoring Systems Based on Both Donor and Recipient Characteristics for Predicting Outcome after Living Donor Liver Transplantation. AB - BACKGROUND AND OBJECTIVES: In order to provide a good match between donor and recipient in liver transplantation, four scoring systems [the product of donor age and Model for End-stage Liver Disease score (D-MELD), the score to predict survival outcomes following liver transplantation (SOFT), the balance of risk score (BAR), and the transplant risk index (TRI)] based on both donor and recipient parameters were designed. This study was conducted to evaluate the performance of the four scores in living donor liver transplantation (LDLT) and compare them with the MELD score. PATIENTS AND METHODS: The clinical data of 249 adult patients undergoing LDLT in our center were retrospectively evaluated. The area under the receiver operating characteristic curves (AUCs) of each score were calculated and compared at 1-, 3-, 6-month and 1-year after LDLT. RESULTS: The BAR at 1-, 3-, 6-month and 1-year after LDLT and the D-MELD and TRI at 1-, 3- and 6-month after LDLT showed acceptable performances in the prediction of survival (AUC>0.6), while the SOFT showed poor discrimination at 6-month after LDLT (AUC = 0.569). In addition, the D-MELD and BAR displayed positive correlations with the length of ICU stay (D-MELD, p = 0.025; BAR, p = 0.022). The SOFT was correlated with the time of mechanical ventilation (p = 0.022). CONCLUSION: The D-MELD, BAR and TRI provided acceptable performance in predicting survival after LDLT. However, even though these scoring systems were based on both donor and recipient parameters, only the BAR provided better performance than the MELD in predicting 1-year survival after LDLT. PMID- 26378788 TI - A Modeling Insight into Adipose-Derived Stem Cell Myogenesis. AB - Adipose-derived stem cells (ASCs) are clinically important in regenerative medicine as they are relatively easy to obtain, are characterized by low morbidity, and can differentiate into myogenic progenitor cells. Although studies have elucidated the principal markers, PAX7, Desmin, MyoD, and MHC, the underlying mechanisms are not completely understood. This motivates the application of computational methods to facilitate greater understanding of such processes. In the following, we present a multi-stage kinetic model comprising a system of ordinary differential equations (ODEs). We sought to model ASC differentiation using data from a static culture, where no strain is applied, and a dynamic culture, where 10% strain is applied. The coefficients of the equations have been modulated by those experimental data points. To correctly represent the trajectories, various switches and a feedback factor based on total cell number have been introduced to better represent the biology of ASC differentiation. Furthermore, the model has then been applied to predict ASC fate for strains different from those used in the experimental conditions and for times longer than the duration of the experiment. Analysis of the results reveals unique characteristics of ASC myogenesis under dynamic conditions of the applied strain. PMID- 26378789 TI - The Problem with Phi: A Critique of Integrated Information Theory. PMID- 26378787 TI - The role of combined SNV and CNV burden in patients with distal symmetric polyneuropathy. AB - PURPOSE: Charcot-Marie-Tooth (CMT) disease is a heterogeneous group of genetic disorders of the peripheral nervous system. Copy-number variants (CNVs) contribute significantly to CMT, as duplication of PMP22 underlies the majority of CMT1 cases. We hypothesized that CNVs and/or single-nucleotide variants (SNVs) might exist in patients with CMT with an unknown molecular genetic etiology. METHODS: Two hundred patients with CMT, negative for both SNV mutations in several CMT genes and for CNVs involving PMP22, were screened for CNVs by high resolution oligonucleotide array comparative genomic hybridization. Whole-exome sequencing was conducted on individuals with rare, potentially pathogenic CNVs. RESULTS: Putatively causative CNVs were identified in five subjects (~2.5%); four of the five map to known neuropathy genes. Breakpoint sequencing revealed Alu-Alu mediated junctions as a predominant contributor. Exome sequencing identified MFN2 SNVs in two of the individuals. CONCLUSION: Neuropathy-associated CNV outside of the PMP22 locus is rare in CMT. Nevertheless, there is potential clinical utility in testing for CNVs and exome sequencing in CMT cases negative for the CMT1A duplication. These findings suggest that complex phenotypes including neuropathy can potentially be caused by a combination of SNVs and CNVs affecting more than one disease-associated locus and contributing to a mutational burden.Genet Med 18 5, 443-451. PMID- 26378790 TI - Tumor Necrosis Factor - Alpha Is Essential for Angiotensin II-Induced Ventricular Remodeling: Role for Oxidative Stress. AB - The functional crosstalk between angiotensin II (Ang II) and tumor necrosis factor (TNF)-alpha has been shown to cause adverse left ventricular remodeling and hypertrophy in hypertension. Previous studies from our lab showed that mice lacking TNF-alpha (TNF-alpha-/-) have attenuated hypertensive response to Ang II; however, the signaling mechanisms involved are not known. In this study, we investigated the signaling pathways involved in the Ang II and TNF-alpha interaction. Chronic Ang II infusion (1 MUg/kg/min, 14 days) significantly increased cardiac collagen I, collagen III, CTGF and TGF-beta mRNA and protein expression in wild-type (WT) mice, whereas these changes were decreased in TNF alpha-/- mice. TNF-alpha-/- mice with Ang II infusion showed reduced myocardial perivascular and interstitial fibrosis compared to WT mice with Ang II infusion. In WT mice, Ang II infusion increased reactive oxygen species formation and the expression of NADPH oxidase subunits, indicating increased oxidative stress, but not in TNF-alpha-/- mice. In addition, treatment with etanercept (8 mg/kg, every 3 days) for two weeks blunted the Ang II-induced hypertension (133 +/- 4 vs 154 +/- 3 mmHg, p<0.05) and cardiac hypertrophy (heart weight to body weight ratio, 4.8 +/- 0.2 vs 5.6 +/- 0.3, p<0.05) in WT mice. Furthermore, Ang II-induced activation of NF-kappaB, p38 MAPK, and JNK were reduced in both TNF-alpha-/- mice and mice treated with etanercept. Together, these findings indicate that TNF alpha contributes to Ang II-induced hypertension and adverse cardiac remodeling, and that these effects are associated with changes in the oxidative stress dependent MAPK/TGF-beta/NF-kappaB pathway. These results may provide new insight into the mechanisms of Ang II and TNF-alpha interaction. PMID- 26378791 TI - Transfusion Patterns in All Patients Admitted to the Intensive Care Unit and in Those Who Die in Hospital: A Descriptive Analysis. AB - While it is known that the use of health care resources increases at the end of life in patients admitted to the Intensive Care Unit (ICU), the allocation of blood products at the end of life has not been described. The objective of this study was to describe overall transfusion patterns in the ICU, and specifically in patients who die in hospital. We conducted a retrospective cohort study of adult patients admitted to the ICU of a university-affiliated hospital, who were discharged or died between November 1, 2006 and June 30, 2012. During the study period, 10,642 patients were admitted at least once to the ICU. Of these patients, 4079 (38.3%) received red blood cells (RBCs), plasma or platelets in the ICU. The ICU mortality rate was 28.1% and in-hospital mortality rate was 32.3%. Among 39,591 blood product units transfused over the course of the study in the ICU (18,144 RBC units, 16,920 plasma units and 4527 platelet units), 46.2% were administered to patients who later died within the same hospitalization (41.2% of RBCs, 50.4% of plasma and 50.8% of platelets). Of all blood product units (RBCs, plasma and platelets) administered in the ICU over the study period, 11% were given within the last 24 hours before death. A large proportion of blood products used in the ICU are administered to patients who ultimately succumb to their illness in hospital, and many of these blood units are given in close proximity to death. PMID- 26378792 TI - Autophagosome Proteins LC3A, LC3B and LC3C Have Distinct Subcellular Distribution Kinetics and Expression in Cancer Cell Lines. AB - LC3s (MAP1-LC3A, B and C) are structural proteins of autophagosomal membranes, widely used as biomarkers of autophagy. Whether these three LC3 proteins have a similar biological role in autophagy remains obscure. We examine in parallel the subcellular expression patterns of the three LC3 proteins in a panel of human cancer cell lines, as well as in normal MRC5 fibroblasts and HUVEC, using confocal microscopy and western blot analysis of cell fractions. In the cytoplasm, there was a minimal co-localization between LC3A, B and C staining, suggesting that the relevant autophagosomes are formed by only one out of the three LC3 proteins. LC3A showed a perinuclear and nuclear localization, while LC3B was equally distributed throughout the cytoplasm and localized in the nucleolar regions. LC3C was located in the cytoplasm and strongly in the nuclei (excluding nucleoli), where it extensively co-localized with the LC3A and the Beclin-1 autophagy initiating protein. Beclin 1 is known to contain a nuclear trafficking signal. Blocking nuclear export function by Leptomycin B resulted in nuclear accumulation of all LC3 and Beclin-1 proteins, while Ivermectin that blocks nuclear import showed reduction of accumulation, but not in all cell lines. Since endogenous LC3 proteins are used as major markers of autophagy in clinical studies and cell lines, it is essential to check the specificity of the antibodies used, as the kinetics of these molecules are not identical and may have distinct biological roles. The distinct subcellular expression patterns of LC3s provide a basis for further studies. PMID- 26378793 TI - Suppression of Hydroxycinnamate Network Formation in Cell Walls of Rice Shoots Grown under Microgravity Conditions in Space. AB - Network structures created by hydroxycinnamate cross-links within the cell wall architecture of gramineous plants make the cell wall resistant to the gravitational force of the earth. In this study, the effects of microgravity on the formation of cell wall-bound hydroxycinnamates were examined using etiolated rice shoots simultaneously grown under artificial 1 g and microgravity conditions in the Cell Biology Experiment Facility on the International Space Station. Measurement of the mechanical properties of cell walls showed that shoot cell walls became stiff during the growth period and that microgravity suppressed this stiffening. Amounts of cell wall polysaccharides, cell wall-bound phenolic acids, and lignin in rice shoots increased as the shoot grew. Microgravity did not influence changes in the amounts of cell wall polysaccharides or phenolic acid monomers such as ferulic acid (FA) and p-coumaric acid, but it suppressed increases in diferulic acid (DFA) isomers and lignin. Activities of the enzymes phenylalanine ammonia-lyase (PAL) and cell wall-bound peroxidase (CW-PRX) in shoots also increased as the shoot grew. PAL activity in microgravity-grown shoots was almost comparable to that in artificial 1 g-grown shoots, while CW-PRX activity increased less in microgravity-grown shoots than in artificial 1 g-grown shoots. Furthermore, the increases in expression levels of some class III peroxidase genes were reduced under microgravity conditions. These results suggest that a microgravity environment modifies the expression levels of certain class III peroxidase genes in rice shoots, that the resultant reduction of CW-PRX activity may be involved in suppressing DFA formation and lignin polymerization, and that this suppression may cause a decrease in cross-linkages within the cell wall architecture. The reduction in intra-network structures may contribute to keeping the cell wall loose under microgravity conditions. PMID- 26378794 TI - Effects of Combined Aerobic and Resistance Exercise on Exercise Capacity, Muscle Strength and Quality of Life in HIV-Infected Patients: A Systematic Review and Meta-Analysis. AB - BACKGROUND: Many HIV-infected patients demonstrate disability and lower aerobic capacity. The inclusion of resistance training combined with aerobic exercise in a single program is known as combined aerobic and resistance exercise (CARE) and seems to be an effective strategy to improve muscle weakness, as well as aerobic capacity in HIV-infected patients. We performed a meta-analysis to investigate the effects of CARE in HIV-infected patients. METHODS: We searched MEDLINE, Cochrane Controlled Trials Register, EMBASE, CINAHL (from the earliest date available to august 2014) for controlled trials that evaluated the effects of CARE in HIV-infected patients. Weighted mean differences (WMD) and 95% confidence intervals (CIs) were calculated, and heterogeneity was assessed using the I2 test. RESULTS: Seven studies met the study criteria. CARE resulted in improvement in Peak VO2 WMD (4.48 mL.kg-1.min-1 95% CI: 2.95 to 6.0), muscle strength of the knee extensors WMD (25.06 Kg 95% CI: 10.46 to 39.66) and elbow flexors WMD (4.44 Kg 95% CI: 1.22 to 7.67) compared with no exercise group. The meta-analyses also showed significant improvement in Health status, Energy/Vitality and physical function domains of quality of life for participants in the CARE group compared with no exercise group. A nonsignificant improvement in social function domain of quality of life was found for participants in the CARE group compared with no exercise group. CONCLUSIONS: Combined aerobic and resistance exercise may improve peak VO2, muscle strength and health status, energy and physical function domains of quality of life and should be considered as a component of care of HIV infected individuals. PMID- 26378796 TI - Effect of Intramuscular Protons, Lactate, and ATP on Muscle Hyperalgesia in Rats. AB - Chronic muscle pain is a significant health problem leading to disability[1]. Muscle fatigue can exacerbate muscle pain. Metabolites, including ATP, lactate, and protons, are released during fatiguing exercise and produce pain in humans. These substances directly activate purinergic (P2X) and acid sensing ion channels (ASICs) on muscle nociceptors, and when combined, produce a greater increase in neuron firing than when given alone. Whether the enhanced effect of combining protons, lactate, and ATP is the sum of individual effects (additive) or more than the sum of individual effects (synergistic) is unknown. Using a rat model of muscle nociceptive behavior, we tested each of these compounds individually over a range of physiologic and supra-physiologic concentrations. Further, we combined all three compounds in a series of dilutions and tested their effect on muscle nociceptive behavior. We also tested a non-hydrolyzable form of ATP (alpha,beta meATP) alone and in combination with lactate and acidic pH. Surprisingly, we found no dose-dependent effect on muscle nociceptive behavior for protons, lactate, or ATP when given alone. We similarly found no effect after application of each two-metabolite combination. Only pH 4 saline and alpha,beta-meATP produced hyperalgesia when given alone. When all 3 substances were combined, however, ATP (2.4MUm), lactate (10mM), and acidic pH (pH 6.0) produced an enhanced effect greater than the sum of the effects of the individual components, i.e. synergism. alpha,beta me ATP (3nmol), on the other hand, showed no enhanced effects when combined with lactate (10mM) or acidic pH (pH 6.0), i.e. additive. These data suggest that combining fatigue metabolites in muscle produces a synergistic effect on muscle nociception. PMID- 26378797 TI - Brief Behavioral Sleep Intervention for Adolescents: An Effectiveness Study. AB - Sleep disturbances are common among adolescents, but there are no brief interventions to treat them. The objective of this study was to evaluate the effectiveness of a brief semistructured, individually delivered sleep intervention to ameliorate adolescents' sleeping difficulties and lengthen sleep duration. All students aged 16-18 years in a high school were screened for sleeping difficulties and 36 students with the highest sleep problem scores were invited to the intervention. Postintervention improvements were observed on self reported and actiwatch-registered sleep duration, self-reported sleep quality and sleep latency, perceived stress and anxiety (all p values < 0.001). However, objectively measured sleep efficiency and sleep latency did not change (p > 0.05). A brief individual sleep intervention can be effective in lengthening sleep duration and improving subjective sleep quality and well-being among adolescents. PMID- 26378795 TI - Heterosexual Transmission of Subtype C HIV-1 Selects Consensus-Like Variants without Increased Replicative Capacity or Interferon-alpha Resistance. AB - Heterosexual transmission of HIV-1 is characterized by a genetic bottleneck that selects a single viral variant, the transmitted/founder (TF), during most transmission events. To assess viral characteristics influencing HIV-1 transmission, we sequenced 167 near full-length viral genomes and generated 40 infectious molecular clones (IMC) including TF variants and multiple non transmitted (NT) HIV-1 subtype C variants from six linked heterosexual transmission pairs near the time of transmission. Consensus-like genomes sensitive to donor antibodies were selected for during transmission in these six transmission pairs. However, TF variants did not demonstrate increased viral fitness in terms of particle infectivity or viral replicative capacity in activated peripheral blood mononuclear cells (PBMC) and monocyte-derived dendritic cells (MDDC). In addition, resistance of the TF variant to the antiviral effects of interferon-alpha (IFN-alpha) was not significantly different from that of non-transmitted variants from the same transmission pair. Thus neither in vitro viral replicative capacity nor IFN-alpha resistance discriminated the transmission potential of viruses in the quasispecies of these chronically infected individuals. However, our findings support the hypothesis that within-host evolution of HIV-1 in response to adaptive immune responses reduces viral transmission potential. PMID- 26378798 TI - Alginate-Iron Speciation and Its Effect on In Vitro Cellular Iron Metabolism. AB - Alginates are a class of biopolymers with known iron binding properties which are routinely used in the fabrication of iron-oxide nanoparticles. In addition, alginates have been implicated in influencing human iron absorption. However, the synthesis of iron oxide nanoparticles employs non-physiological pH conditions and whether nanoparticle formation in vivo is responsible for influencing cellular iron metabolism is unclear. Thus the aims of this study were to determine how alginate and iron interact at gastric-comparable pH conditions and how this influences iron metabolism. Employing a range of spectroscopic techniques under physiological conditions alginate-iron complexation was confirmed and, in conjunction with aberration corrected scanning transmission electron microscopy, nanoparticles were observed. The results infer a nucleation-type model of iron binding whereby alginate is templating the condensation of iron-hydroxide complexes to form iron oxide centred nanoparticles. The interaction of alginate and iron at a cellular level was found to decrease cellular iron acquisition by 37% (p < 0.05) and in combination with confocal microscopy the alginate inhibits cellular iron transport through extracellular iron chelation with the resulting complexes not internalised. These results infer alginate as being useful in the chelation of excess iron, especially in the context of inflammatory bowel disease and colorectal cancer where excess unabsorbed luminal iron is thought to be a driver of disease. PMID- 26378799 TI - Enantioselective Iodine(III)-Mediated Synthesis of alpha-Tosyloxy Ketones: Breaking the Selectivity Barrier. AB - The development of practical methods to access chiral nonracemic alpha substituted ketones is of particular importance due to their ubiquitous nature. Unprecedented levels of enantioselectivity are reported for the synthesis of alpha-tosyloxy ketones, using enol esters and chiral iodine(III) reagents. The reaction can be performed under both stoichiometric and catalytic conditions. These results suggest widely different reaction mechanisms for the reaction of ketones versus enol esters, supporting recent computational insights. PMID- 26378800 TI - Correction: AAA-ATPase FIDGETIN-LIKE 1 and Helicase FANCM Antagonize Meiotic Crossovers by Distinct Mechanisms. PMID- 26378801 TI - Correction: A Multi-country Study of the Household Willingness-to-Pay for Dengue Vaccines: Household Surveys in Vietnam, Thailand, and Colombia. PMID- 26378802 TI - Interferon-Gamma Release Assay: An Effective Tool to Detect Early Toxoplasma gondii Infection in Mice. AB - Early diagnosis of Toxoplasma gondii infection before the formation of tissue cysts is vital for treatment, as drugs available for toxoplasmosis cannot kill bradyzoites contained in the cysts. However, current methods, such as antibody based ELISA, are ineffective for detection of early infection. Here, we developed an interferon-gamma release assay (IGRA), measuring the IFN-gamma released by T lymphocytes stimulated by Toxoplasma antigen peptides in vitro, for the detection of T. gondii infection in mice. Splenocytes isolated from infected mice were stimulated by peptides derived from dense granule proteins GRA4 and GRA6 and rhoptry protein ROP7, and released IFN-gamma was measured by ELISA. Results showed that both acute and chronic infection could be detected by IGRA. More importantly, IGRA detected infection as early as the third day post infection; while serum IgM and IgG were detected 9 days and 13 days post infection, respectively. Our findings demonstrated that an IGRA-positive and ELISA-negative sample revealed an early infection, indicating the combination of IGRA and ELISA can be employed for the early diagnosis of T. gondii infection in human beings, cats and livestock. PMID- 26378803 TI - Effects of tonal language background on tests of temporal sequencing in children. AB - OBJECTIVE: The aims of the present study were to determine the effects of language background on the performance of the pitch pattern sequence test (PPST) and duration pattern sequence test (DPST). As temporal order sequencing may be affected by age and working memory, these factors were also studied. DESIGN: Performance of tonal and non-tonal language speakers on PPST and DPST were compared. STUDY SAMPLE: Twenty-eight native Mandarin (tonal language) speakers and twenty-nine native Malay (non-tonal language) speakers between seven to nine years old participated in this study. RESULTS: The results revealed that relative to native Malay speakers, native Mandarin speakers demonstrated better scores on the PPST in both humming and verbal labeling responses. However, a similar language effect was not apparent in the DPST. An age effect was only significant in the PPST (verbal labeling). Finally, no significant effect of working memory was found on the PPST and the DPST. CONCLUSION: These findings suggest that the PPST is affected by tonal language background, and highlight the importance of developing different normative values for tonal and non-tonal language speakers. PMID- 26378804 TI - Quantitative Adverse Outcome Pathway Analysis of Hatching in Zebrafish with CuO Nanoparticles. AB - This study develops and evaluates a mechanistic model of the hatching of zebrafish eggs that were exposed to CuO engineered nanoparticles (ENP) in a high throughput screening system and places this model in an adverse outcome pathway (AOP) that also includes CuO ENP dissolution and Cu bioaccumulation. Cu(2+) inhibits the proteolytic activity of Zebrafish Hatching Enzyme 1 and thereby delay or impair hatching success. This study demonstrates that noncompetitive inhibition kinetics describe the impact of dissolved Cu on hatching; it is estimated that indefinitely long exposure to 1.88 MUM dissolved Cu in the environment reduces hatching enzyme activity by 50%. The complexity arising from CuO ENP dissolution and CuO ENP assisted bioaccumulation of Cu has led to apparently contradictory findings about ion versus "nano" effects on hatching. Model-mediated data analyses indicate that, relative to copper salts, CuO ENPs increase the uptake rates of Cu into the perivitelline space up to 8 times. The toxicity assessment framework in this study can be adapted to accommodate other types of toxicant, environmental samples and other aquatic oviparous species. PMID- 26378805 TI - Monte Carlo comparison of x-ray and proton CT for range calculations of proton therapy beams. AB - Proton computed tomography (CT) has been described as a solution for imaging the proton stopping power of patient tissues, therefore reducing the uncertainty of the conversion of x-ray CT images to relative stopping power (RSP) maps and its associated margins. This study aimed to investigate this assertion under the assumption of ideal detection systems. We have developed a Monte Carlo framework to assess proton CT performances for the main steps of a proton therapy treatment planning, i.e. proton or x-ray CT imaging, conversion to RSP maps based on the calibration of a tissue phantom, and proton dose simulations. Irradiations of a computational phantom with pencil beams were simulated on various anatomical sites and the proton range was assessed on the reference, the proton CT-based and the x-ray CT-based material maps. Errors on the tissue's RSP reconstructed from proton CT were found to be significantly smaller and less dependent on the tissue distribution. The imaging dose was also found to be much more uniform and conformal to the primary beam. The mean absolute deviation for range calculations based on x-ray CT varies from 0.18 to 2.01 mm depending on the localization, while it is smaller than 0.1 mm for proton CT. Under the assumption of a perfect detection system, proton range predictions based on proton CT are therefore both more accurate and more uniform than those based on x-ray CT. PMID- 26378806 TI - Multicomponent Self-Assembled Metal-Organic [3]Rotaxanes. AB - A set of environmentally responsive metal-organic [3]rotaxanes is described. These mechanically interlocked macromolecules may be prepared in quantitative yield via a one-pot procedure involving treatment of a flexible tetracationic macrocycle, known as the Texas-sized molecular box, with tri-1,3,5 benzenetricarboxylate anion and silver cations (Ag(+)). The use of this three component mixture gives rise to a metal-organic [3]rotaxane via a self-assembly process that occurs under ambient conditions in DMSO-d6 solution. The complex is stable in the presence of excess TFA. However, disassembly of the [3]rotaxane to produce anion-box associated entities may be triggered by adding a competitive counteranionic species (e.g., I(-)). Adding excess Ag(+) serves to reverse this decomplexation process. The nature of the [3]rotaxane complex could be fine-tuned via application of an external stimulus. Increasing the temperature or adding small molecules (e.g., D2O, methanol-d4, acetonitrile-d3, DMF-d7, acetone-d6, or THF-d8) to the initial DMSO-d6 solution induces conformational flipping of the macrocycle within the overall complex (e.g., from limiting chair to chairlike forms). Support for the molecular stimuli responsive nature of the various structures came from solution-phase one- and two-dimensional ((1)H, 1D and 2D NOESY) NMR spectroscopic studies carried out in DMSO-d6. The core metal-linked rotaxane unit was characterized via single-crystal X-ray diffraction analysis. Initial evidence that the present self-assembly process is not limited to the use of the Ag(+) cation came from studies involving Cd(2+); this replacement results in formation of 2D metal-organic rotaxane-containing frameworks (MORFs). PMID- 26378807 TI - DNA-Directed Antibody Immobilization for Enhanced Detection of Single Viral Pathogens. AB - Here, we describe the use of DNA-conjugated antibodies for rapid and sensitive detection of whole viruses using a single-particle interferometric reflectance imaging sensor (SP-IRIS), a simple, label-free biosensor capable of imaging individual nanoparticles. First, we characterize the elevation of the antibodies conjugated to a DNA sequence on a three-dimensional (3-D) polymeric surface using a fluorescence axial localization technique, spectral self-interference fluorescence microscopy (SSFM). Our results indicate that using DNA linkers results in significant elevation of the antibodies on the 3-D polymeric surface. We subsequently show the specific detection of pseudotyped vesicular stomatitis virus (VSV) as a model virus on SP-IRIS platform. We demonstrate that DNA conjugated antibodies improve the capture efficiency by achieving the maximal virus capture for an antibody density as low as 0.72 ng/mm(2), whereas for unmodified antibody, the optimal virus capture requires six times greater antibody density on the sensor surface. We also show that using DNA conjugated anti-EBOV GP (Ebola virus glycoprotein) improves the sensitivity of EBOV-GP carrying VSV detection compared to directly immobilized antibodies. Furthermore, utilizing a DNA surface for conversion to an antibody array offers an easier manufacturing process by replacing the antibody printing step with DNA printing. The DNA-directed immobilization technique also has the added advantages of programmable sensor surface generation based on the need and resistance to high temperatures required for microfluidic device fabrication. These capabilities improve the existing SP-IRIS technology, resulting in a more robust and versatile platform, ideal for point-of-care diagnostics applications. PMID- 26378808 TI - Approaches to isolation and molecular characterization of disseminated tumor cells. AB - Micrometastatic cells in the bone marrow, now usually referred to as "disseminated tumor cells (DTCs)", can be detected in early stage cancer patients. It has been hypothesized that DTCs represent key intermediates in the metastatic process as possible precursors of bone and visceral metastases, and are indicators of metastatic potential. Indeed, multiple clinical studies have unequivocally demonstrated the prognostic value of these cells in breast and other cancers, as DTCs have been associated with adverse outcomes, including inferior overall and disease-free survival. Despite this established clinical significance, the molecular nature of DTCs remains elusive. The complexity of the bone marrow poses a unique challenge in the isolation and direct characterization of these rare cells. However, recent advances in rare-cell technology along with technical improvements in analyzing limited cell inputs have enabled the molecular profiling of DTCs. In this review, we discuss research featuring the isolation and genomic analysis of DTCs. Emerging work on the molecular characterization of DTCs is now providing new insights into the biology of these cells. PMID- 26378809 TI - Comparative genomic analysis reveals bilateral breast cancers are genetically independent. AB - Bilateral breast cancer (BBC) poses a major challenge for oncologists because of the cryptic relationship between the two lesions. The purpose of this study was to determine the origin of the contralateral breast cancer (either dependent or independent of the index tumor). Here, we used ultra-deep whole-exome sequencing and array comparative genomic hybridization (aCGH) to study four paired samples of BBCs with different tumor subtypes and time intervals between the developments of each tumor. We used two paired primary breast tumors and corresponding metastatic liver lesions as the control. We tested the origin independent nature of BBC in three ways: mutational concordance, mutational signature clustering, and clonality analysis using copy number profiles. We found that the paired BBC samples had near-zero concordant mutation rates, which were much lower than those of the paired primary/metastasis samples. The results of a mutational signature analysis also suggested that BBCs are independent of one another. A clonality analysis using aCGH data further revealed that paired BBC samples was clonally independent, in contrast to clonal related origin found for paired primary/metastasis samples. Our preliminary findings show that BBCs in Han Chinese women are origin independent and thus should be treated separately. PMID- 26378810 TI - sMEK1 inhibits endothelial cell proliferation by attenuating VEGFR-2-dependent Akt/eNOS/HIF-1alpha signaling pathways. AB - The suppressor of MEK null (sMEK1) protein possesses pro-apoptotic activities. In the current study, we reveal that sMEK1 functions as a novel anti-angiogenic factor by suppressing vascular endothelial growth factor (VEGF)-induced cell proliferation, migration, and capillary-like tubular structure in vitro. In addition, sMEK1 inhibited the phosphorylation of the signaling components up- and downstream of Akt, including phospholipase Cgamma1 (PLC-gamma1), 3 phosphoinositide-dependent protein kinase 1 (PDK1), endothelial nitric oxide synthetase (eNOS), and hypoxia-inducible factor 1 (HIF-1alpha) during ovarian tumor progression via binding with vascular endothelial growth factor receptor 2 (VEGFR-2). Furthermore, sMEK1 decreased tumor vascularity and inhibited tumor growth in a xenograft human ovarian tumor model. These results supply convincing evidence that sMEK1 controls endothelial cell function and subsequent angiogenesis by suppressing VEGFR-2-mediated PI3K/Akt/eNOS signaling pathway. Taken together, our results clearly suggest that sMEK1 might be a novel anti angiogenic and anti-tumor agent for use in ovarian tumor. PMID- 26378813 TI - Molecular Dynamics Study of the Structure, Flexibility, and Hydrophilicity of PETIM Dendrimers: A Comparison with PAMAM Dendrimers. AB - A new class of dendrimers, the poly(propyl ether imine) (PETIM) dendrimer, has been shown to be a novel hyperbranched polymer having potential applications as a drug delivery vehicle. Structure and dynamics of the amine terminated PETIM dendrimer and their changes with respect to the dendrimer generation are poorly understood. Since most drugs are hydrophobic in nature, the extent of hydrophobicity of the dendrimer core is related to its drug encapsulation and retention efficacy. In this study, we carry out fully atomistic molecular dynamics (MD) simulations to characterize the structure of PETIM (G2-G6) dendrimers in salt solution as a function of dendrimer generation at different protonation levels. Structural properties such as radius of gyration (Rg), radial density distribution, aspect ratio, and asphericity are calculated. In order to assess the hydrophilicity of the dendrimer, we compute the number of bound water molecules in the interior of dendrimer as well as the number of dendrimer-water hydrogen bonds. We conclude that PETIM dendrimers have relatively greater hydrophobicity and flexibility when compared with their extensively investigated PAMAM counterparts. Hence PETIM dendrimers are expected to have stronger interactions with lipid membranes as well as improved drug encapsulation and retention properties when compared with PAMAM dendrimers. We compute the root mean-square fluctuation of dendrimers as well as their entropy to quantify the flexibility of the dendrimer. Finally we note that structural and solvation properties computed using force field parameters derived based on the CHARMM general purpose force field were in good quantitative agreement with those obtained using the generalized Amber force field (GAFF). PMID- 26378814 TI - Medically Unexplained Symptoms: Barriers to Effective Treatment When Nothing Is the Matter. AB - Patients with symptoms that elude medical explanation are a perennial challenge to practicing physicians of all disciplines. Articles appear virtually monthly advising physicians how to care for them. Efforts at postgraduate education have attempted to ameliorate the situation but have shown limited or disappointing results at best. Physicians continue either to avoid these patients or to resort to a "seat-of-the-pants" approach to management. Literature on patients with medically unexplained symptoms, along with extensive experience consulting with primary care physicians, suggests that it is not primarily lack of physician skills but rather a series of barriers to adequate care that may account for suboptimal management. Barriers to implementation of effective care reside in the nature of medical education, the doctor-patient relationship, heterogeneity of symptoms and labels, changes in the health care system, and other variables. These impediments are considered here, with suggested potential remedies, in the conviction that the proper care of patients with medically unexplained symptoms can, among other things, bring satisfaction to both the patient and the physician, and help to reduce ineffective health resource utilization. PMID- 26378815 TI - Measurement and prediction of quantum coherence effects in biological processes. PMID- 26378811 TI - Non-random aneuploidy specifies subgroups of pilocytic astrocytoma and correlates with older age. AB - Pilocytic astrocytoma (PA) is the most common brain tumor in children but is rare in adults, and hence poorly studied in this age group. We investigated 222 PA and report increased aneuploidy in older patients. Aneuploid genomes were identified in 45% of adult compared with 17% of pediatric PA. Gains were non-random, favoring chromosomes 5, 7, 6 and 11 in order of frequency, and preferentially affecting non-cerebellar PA and tumors with BRAF V600E mutations and not with KIAA1549-BRAF fusions or FGFR1 mutations. Aneuploid PA differentially expressed genes involved in CNS development, the unfolded protein response, and regulators of genomic stability and the cell cycle (MDM2, PLK2),whose correlated programs were overexpressed specifically in aneuploid PA compared to other glial tumors. Thus, convergence of pathways affecting the cell cycle and genomic stability may favor aneuploidy in PA, possibly representing an additional molecular driver in older patients with this brain tumor. PMID- 26378816 TI - Identification of an inflammatory bowel disease patient with a deep vein thrombosis and an altered clot lysis profile. AB - Patients with inflammatory bowel diseases (IBD), a chronic inflammatory disease characterized by flares and remission, are prone to develop thrombosis. The mechanism behind this prothrombotic state is not completely understood but is definitely multifactorial and linked with excessive inflammation observed in these patients. So far, no biomarker exists to select among IBD patients those with and increased risk for thrombosis. Corticosteroid therapy, given as rescue IBD treatment, is known to increase the thrombotic risk, whereas for antitumor necrosis factor (TNF)-alpha therapy such as infliximab, given to induce and maintain remission in IBD, the results are inconclusive. Here, we describe a 31 year-old IBD patient who developed a deep vein thrombosis. We determined the clot lysis profiles before and after developing thrombosis. We showed that a global functional clot lysis assay can be used as a tool to identify IBD patients who may benefit from thromboprophylactic therapy. PMID- 26378812 TI - DNA-mediated adjuvant immunotherapy extends survival in two different mouse models of myeloid malignancies. AB - We have previously shown that a specific promyelocytic leukemia-retinoic acid receptor alpha (PML-RARA) DNA vaccine combined with all-trans retinoic acid (ATRA) increases the number of long term survivors with enhanced immune responses in a mouse model of acute promyelocytic leukemia (APL). This study reports the efficacy of a non-specific DNA vaccine, pVAX14Flipper (pVAX14), in both APL and high risk myelodysplastic syndrome (HR-MDS) models. PVAX14 is comprised of novel immunogenic DNA sequences inserted into the pVAX1 therapeutic plasmid. APL mice treated with pVAX14 combined with ATRA had increased survival comparable to that obtained with a specific PML-RARA vaccine. Moreover, the survival advantage correlated with decreased PML-RARA transcript levels and increase in anti-RARA antibody production. In HR-MDS mice, pVAX14 significantly improved survival and reduced biomarkers of leukemic transformation such as phosphorylated mitogen activated protein/extracellular signal-regulated kinase kinase (MEK) 1. In both preclinical models, pVAX14 vaccine significantly increased interferon gamma (IFNgamma) production, memory T-cells (memT), reduced the number of colony forming units (CFU) and increased expression of the adapter molecule signalling to NF-kappaB, MyD88. These results demonstrate the adjuvant properties of pVAX14 providing thus new approaches to improve clinical outcome in two different models of myeloid malignancies, which may have potential for a broader applicability in other cancers. PMID- 26378817 TI - Bioprostethic mitral valve thrombosis due to oral contraceptive drug use and management with ultra-slow thrombolytic therapy. AB - Prosthetic valve thrombosis is a severe complication, which usually occurs in inadequately anticoagulated patients. Mechanical valve thrombosis is more common than bioprosthetic valve thrombosis (BVT). Oral contraceptive drugs are associated with increased risk of thromboembolism in women. The possible association between oral contraceptive drug use and BVT has never been reported before. We present a case of obstructive BVT occurring after the use of an oral contraceptive drug and successful management with ultra-slow thrombolytic therapy. PMID- 26378819 TI - Differential effects of main error correction versus secondary error correction on motor pattern of running. AB - The aim of this study was to gain a better understanding of how the run pattern varies as a consequence to main error correction versus secondary error correction. Twenty-two university students were randomly assigned to one of two training-conditions: 'main error' (ME) and 'secondary error' (SE) correction. The rear-foot strike at touchdown was hypothesized as the 'main error', whereas an incorrect shoulder position (i.e., behind the base of support) as the 'secondary error'. In order to evaluate any changes in run pattern at the foot touchdown instant, the ankle, knee and hip joint angles, the height of toe and heel (with respect to the ground), and the horizontal distance from the heel to the projected center of mass on the ground were measured. After the training intervention, the ME group showed a significant improvement in the run pattern at the foot touchdown instant in all kinematic parameters, whereas no significant changes were found in the SE group. The results support the hypothesis that the main error can have a greater influence on the movement patterns than a secondary error. Furthermore, the findings highlight that a correct diagnosis and the correction of the 'main error' are fundamental for greater run pattern improvement. PMID- 26378818 TI - Caffeic Acid Phenethyl Ester inhibit Hepatic Fibrosis by Nitric Oxide Synthase and Cystathionine Gamma-Lyase in Rats. AB - BACKGROUND: Our aim was to study the effect of caffeic acid phenethyl ester (CAPE) on iNOS and cystathionine gamma-lyase (CSE) of hepatic fibrosis rat, and discuss the anti-hepatic fibrosis mechanism of caffeic acid phenethyl ester. MATERIAL AND METHODS: We observed changes of NO and H2S in serum of hepatic fibrosis rats. Enzyme-linked immunosorbent assay was used to test OD value of iNOS and CSE in serum of each. The expressions of iNOS and CSE protein in the liver were also detected by immunohistochemistry. RESULTS: Compared with the model group, the expression of NO and iNOS was decreased obviously and the level of H2S and CSE was increased in the CAPE group. CONCLUSIONS: CAPE has the effect of anti-hepatic fibrosis, which can be realized through adjusting the expression level of iNOS and CSE. PMID- 26378820 TI - Strength or power, which is more important to prevent slip-related falls? AB - Falls are a serious health and medical concern facing older adults worldwide. Both muscle strength and power have been related to falls among older adults. The primary purpose of this study was to identify which one of these two muscular performances is more important in preventing a slip-related fall. Twenty-six healthy young adults participated in this study. Their muscle strength (torque) and power capacities were assessed at the right knee under maximum voluntary isometric (flexion and extension) and isokinetic (concentric extension and flexion at three different contraction speeds: 60 deg/s, 120 deg/s, and 180 deg/s) contractions, respectively. They were then subjected to an identical and unannounced slip during gait on a treadmill under the protection of a safety harness after walking regularly for five times on the treadmill. Accuracy of predicting slip outcome (fall vs. recovery) was examined for each muscle performance measurement using logistic regression. Results showed that overall the joint power capacity measurements predicted the slip outcome among these subjects with higher accuracy than did the joint torque capacity measurements. Such results suggested that muscle power could be more closely related to a fall initiated by a slip during gait. The findings from the present study could provide guidance to identify individuals at increased risk of falling using the joint power capacity measurement and to design effective fall prevention training paradigms aiming at maximizing muscle power among older adults and others with physical disabilities. PMID- 26378821 TI - Intergenerational Social Networks and Health Behaviors Among Children Living in Public Housing. AB - OBJECTIVES: In a survey of families living in public housing, we investigated whether caretakers' social networks are linked with children's health status. METHODS: In 2011, 209 children and their caretakers living in public housing in suburban Montgomery County, Maryland, were surveyed regarding their health and social networks. We used logistic regression models to examine the associations between the perceived health composition of caretaker social networks and corresponding child health characteristics (e.g., exercise, diet). RESULTS: With each 10% increase in the proportion of the caretaker's social network that exercised regularly, the child's odds of exercising increased by 34% (adjusted odds ratio = 1.34; 95% confidence interval = 1.07, 1.69) after the caretaker's own exercise behavior and the composition of the child's peer network had been taken into account. Although children's overweight or obese status was associated with caretakers' social networks, the results were no longer significant after adjustment for caretakers' own weight status. CONCLUSIONS: We found that caretaker social networks are independently associated with certain aspects of child health, suggesting the importance of the broader social environment for low income children's health. PMID- 26378822 TI - Differences by Sexual Orientation in Expectations About Future Long-Term Care Needs Among Adults 40 to 65 Years Old. AB - OBJECTIVES: We examined whether and how lesbian, gay, and bisexual (LGB) adults between 40 and 65 years of age differ from heterosexual adults in long-term care (LTC) expectations. METHODS: Our data were derived from the 2013 National Health Interview Survey. We used ordered logistic regression to compare the odds of expected future use of LTC among LGB (n = 297) and heterosexual (n = 13 120) adults. We also used logistic regression models to assess the odds of expecting to use specific sources of care. All models controlled for key socioeconomic characteristics. RESULTS: Although LGB adults had greater expectations of needing LTC in the future than their heterosexual counterparts, that association was largely explained by sociodemographic and health differences. After control for these differentials, LGB adults were less likely to expect care from family and more likely to expect to use institutional care in old age. CONCLUSIONS: LGB adults may rely more heavily than heterosexual adults on formal systems of care. As the older population continues to diversify, nursing homes and assisted living facilities should work to ensure safety and culturally sensitive best practices for older LGB groups. PMID- 26378823 TI - "Nudges" to Prevent Behavioral Risk Factors Associated With Major Depressive Disorder. AB - Major depressive disorder-colloquially called "depression"-is a primary global cause of disability. Current preventive interventions, such as problem-solving therapy, are effective but also expensive. "Nudges" are easy and cheap interventions for altering behavior. We have explored how nudging can reduce three behavioral risk factors of depression: low levels of physical activity, inappropriate coping mechanisms, and inadequate maintenance of social ties. These nudges use cognitive biases associated with these behavioral risks, such as valuing the present more than the future, following the herd or the norm, making different choices in light of equivalent conditions, and deciding on the basis of salience or attachment to status quo. PMID- 26378824 TI - The Laugh Model: Reframing and Rebranding Public Health Through Social Media. AB - OBJECTIVES: We examined the use of low-cost social media platforms in communicating public health messages and outline the laugh model, a framework through which public health organizations can reach and engage communities. METHODS: In August 2014, we developed an online campaign (Web site and social media) to help promote healthy family meals in Utah in conjunction with the state and local health departments. RESULTS: By the end of September 2014, a total of 3641 individuals had visited the Utahfamilymeals.org Web site. Facebook ads reached a total of 29 078 people, and 56 900 people were reached through Twitter ads. The per-person price of the campaign was 0.2 cents, and the total estimated target population reach was between 10% and 12%. CONCLUSIONS: There are 3 key takeaways from our campaign: use of empowering and engaging techniques may be more effective than use of educational techniques; use of social media Web sites and online marketing tactics can enhance collaboration, interdisciplinary strategies, and campaign effectiveness; and use of social media as a communication platform is often preferable to use of mass media in terms of cost effectiveness, more precise evaluations of campaign success, and increased sustainability. PMID- 26378825 TI - Women-Centered Drug Treatment Services and Need in the United States, 2002-2009. AB - OBJECTIVES: We examined options and need for women-centered substance use disorder treatment in the United States between 2002 and 2009. METHODS: We obtained characteristics of facilities from the National Survey of Substance Abuse Treatment Services and treatment need data from the National Survey on Drug Use and Health. We also examined differences in provision of women-centered programs by urbanization level in data from the National Center for Health Statistics 2006 Rural-Urban County Continuum. RESULTS: Of the 13 000 facilities surveyed annually, the proportion offering women-centered services declined from 43% in 2002 to 40% in 2009 (P < .001). Urban location, state population size, and Medicaid payment predicted provision of such services as trauma-related and domestic violence counseling, child care, and housing assistance (all, P < .001). Prevalence of women with unmet need ranged from 81% to 95% across states. CONCLUSIONS: Change in availability of women-centered drug treatment services was minimal from 2002 to 2009, even though need for treatment was high in all states. PMID- 26378826 TI - Racial/Ethnic Disparities in Cumulative Environmental Health Impacts in California: Evidence From a Statewide Environmental Justice Screening Tool (CalEnviroScreen 1.1). AB - OBJECTIVES: We used an environmental justice screening tool (CalEnviroScreen 1.1) to compare the distribution of environmental hazards and vulnerable populations across California communities. METHODS: CalEnviroScreen 1.1 combines 17 indicators created from 2004 to 2013 publicly available data into a relative cumulative impact score. We compared cumulative impact scores across California zip codes on the basis of their location, urban or rural character, and racial/ethnic makeup. We used a concentration index to evaluate which indicators were most unequally distributed with respect to race/ethnicity and poverty. RESULTS: The unadjusted odds of living in one of the 10% most affected zip codes were 6.2, 5.8, 1.9, 1.8, and 1.6 times greater for Hispanics, African Americans, Native Americans, Asian/Pacific Islanders, and other or multiracial individuals, respectively, than for non-Hispanic Whites. Environmental hazards were more regressively distributed with respect to race/ethnicity than poverty, with pesticide use and toxic chemical releases being the most unequal. CONCLUSIONS: Environmental health hazards disproportionately burden communities of color in California. Efforts to reduce disparities in pollution burden can use simple screening tools to prioritize areas for action. PMID- 26378827 TI - Mary Steichen Calderone (1904-1998): Advocate for Sex Education. PMID- 26378828 TI - A Randomized Comparative Effectiveness Trial for Preventing Type 2 Diabetes. AB - OBJECTIVES: We evaluated the weight loss effectiveness of a YMCA model for the Diabetes Prevention Program (DPP) lifestyle intervention. METHODS: Between July 2008 and November 2010, we individually randomized 509 overweight or obese, low income, nondiabetic adults with elevated blood glucose in Indianapolis, Indiana, to receive standard care plus brief lifestyle counseling or be offered a group based YMCA adaptation of the DPP (YDPP). Primary outcome was mean weight loss difference at 12 months. In our intention-to-treat analyses, we used longitudinal linear or logistic regression, multiply imputing missing observations. We used instrumental variables regression to estimate weight loss effectiveness among participants completing 9 or more intervention lessons. RESULTS: In the YDPP arm, 161 (62.6%) participants attended >= 1 lesson and 103 (40.0%) completed 9 or more lessons. In intention-to-treat analysis, mean 12-month weight loss was 2.3 kilograms (95% confidence interval [CI] = 1.1, 3.4 kg) more for the YDPP arm than for standard care participants. In instrumental variable analyses, persons attending 9 or more lessons had a 5.3-kilogram (95% CI = 2.8, 7.9 kg) greater weight loss than did those with standard care alone. CONCLUSIONS: The YMCA model for DPP delivery achieves meaningful weight loss at 12 months among low-income adults. PMID- 26378829 TI - The Rikers Island Hot Spotters: Defining the Needs of the Most Frequently Incarcerated. AB - OBJECTIVES: We used "hot spotting" to characterize the persons most frequently admitted to the New York City jail system in 2013. METHODS: We used our Correctional Health Services electronic health record to identify 800 patients admitted in 2013 who returned most since November 2008. We compared them to a randomly selected control group of 800 others admitted in 2013, by using descriptive statistics and cross-tabulations, including data through December 2014. RESULTS: The frequently incarcerated individuals had a median of 21 incarcerations (median duration 11 days), representing 18 713 admissions and $129 million in custody and health costs versus $38 million for the controls. The frequently incarcerated were significantly older (42 vs 35 years), and more likely to have serious mental illness (19% vs 8.5%) and homelessness (51.5% vs 14.7%) in their record. Significant substance use was highly prevalent (96.9% vs 55.6%). Most top criminal charges (88.7%) for the frequently incarcerated were misdemeanors; assault charges were less common (2.8% vs 10.4%). CONCLUSIONS: Frequently incarcerated persons have chronic mental health and substance use problems, their charges are generally minor, and incarceration is costly. Tailored supportive housing is likely to be less costly and improve outcomes. PMID- 26378830 TI - Weighted Multilevel Models: A Case Study. PMID- 26378831 TI - A Call to Shift the Public Health Focus Away From Weight. PMID- 26378832 TI - What Women Want: A Qualitative Study of Contraception in Jail. AB - OBJECTIVES: We undertook this study to understand women's perceptions of receiving contraception at Rikers Island Jail. METHODS: We conducted semi structured in-depth interviews in 2011 to 2012 with 32 women incarcerated at Rikers Island Jail. We analyzed the data using standard qualitative techniques. RESULTS: Almost all participants believed that contraception should be provided at the jail. However, many said they would hesitate to use these services themselves. Reservations were caused in part by women's negative views of health care services at the jail. Fears about the safety of birth control, difficulties associated with follow-up in the community, and desire for pregnancy were other factors that influenced interest in accepting contraception. CONCLUSIONS: Contraception at the jail must be provided by trusted medical providers delivering high quality care with the goal of allowing women to control their own fertility; this would ensure that women could access birth control and cease using birth control when desired. PMID- 26378833 TI - Public Health and Legal Arguments in Favor of a Policy to Cap the Portion Sizes of Sugar-Sweetened Beverages. AB - In 2012, the New York City Board of Health passed a regulation prohibiting the sale of sugar-sweetened beverages in containers above 16 ounces in the city's food service establishments. The beverage industry and various retailers sued the city to prevent enforcement of the law, arguing that the board had overstepped its authority. In June 2014, the state's highest court agreed and struck down the regulation. Here we report the results of a content analysis of the public testimony related to the case submitted to the New York City Department of Mental Health and Hygiene. We identified major arguments in support of and against the sugar-sweetened beverage portion limit policy. We offer legal and scientific arguments that challenge the major anti-policy arguments and contend that, although this policy was not implemented in New York City, it can be legally pursued by other legislatures. PMID- 26378834 TI - Evaluating the Use of an Electronic Death Registration System for Mortality Surveillance During and After Hurricane Sandy: New York City, 2012. AB - OBJECTIVES: We evaluated the use of New York City's (NYC's) electronic death registration system (EDRS) to conduct mortality surveillance during and after Hurricane Sandy. METHODS: We used Centers for Disease Control and Prevention guidelines for surveillance system evaluation to gather evidence on usefulness, flexibility, stability, timeliness, and quality. We assessed system components, interviewed NYC Health Department staff, and analyzed 2010 to 2012 death records. RESULTS: Despite widespread disruptions, NYC's EDRS was stable and collected timely mortality data that were adapted to provide storm surveillance with minimal additional resources. Direct-injury fatalities and trends in excess all cause mortality were rapidly identified, providing useful information for response; however, the time and burden of establishing reports, adapting the system, and identifying indirect deaths limited surveillance. CONCLUSIONS: The NYC Health Department successfully adapted its EDRS for near real-time disaster related mortality surveillance. Retrospective assessment of deaths, advanced methods for case identification and analysis, standardized reports, and system enhancements will further improve surveillance. Local, state, and federal partners would benefit from partnering with vital records to develop EDRSs for surveillance and to promote ongoing evaluation. PMID- 26378835 TI - Plax Responds. PMID- 26378836 TI - Access to Dental Services for People Using a Wheelchair. AB - OBJECTIVES: We investigated the perspectives of people using a wheelchair and their difficulties in accessing dental services. METHODS: Our participatory research was on the basis of a partnership between people using a wheelchair, dental professionals, and academic researchers. Partners were involved in a committee that provided advice at all stages of the project. Our team adopted a qualitative descriptive design. Between October 2011 and October 2012 we conducted semistructured individual interviews with 13 adults who lived in Montreal, Quebec, Canada, and used a wheelchair full time. We audio-recorded and transcribed verbatim interviews, and we interpreted data using an inductive thematic analysis. RESULTS: Oral health is of heightened importance to this group of people, who tend to use their mouth as a "third hand." We identified successive challenges in accessing dental services: finding a dentist and being accepted, organizing transportation, entering the building and circulating inside, interacting with the dental staff, transferring and overcoming discomfort on the dental chair, and paying for the treatments. CONCLUSIONS: Governments, dental professional bodies, dental schools, and researchers should work with groups representing wheelchair users to improve access to dental services. PMID- 26378837 TI - Important Considerations for Addressing LGBT Health Care Competency. PMID- 26378838 TI - Voluntary, Nonintentional Dehydration and Health. PMID- 26378839 TI - The Life Stories of Homeless Youths. PMID- 26378840 TI - Trajectories of Depressive Symptoms in Canadian Emerging Adults. AB - OBJECTIVES: We identified courses of depressive symptoms in an epidemiological sample of emerging adults. METHODS: We used latent class growth modeling to identify trajectories of depressive symptoms measured by the 12-item Center for Epidemiological Studies Depression Scale (CES-D) during a 14-year follow-up of 2825 Canadian youths aged 10 to 25 years enrolled in the National Longitudinal Survey of Children and Youth between 1994 and 2009. RESULTS: After adjustment for youth, parent, and family factors, the 3 distinct trajectories of depressive symptoms were minimal (55%; CES-D < 6), subclinical (39%; CES-D = 9-13), and clinical (6%; CES-D > 18). All trajectories exhibited a parallel course, with peak symptoms at 15 to 17 years of age. Subclinical and clinical symptoms were more common than minimal symptoms in female youths and in respondents with lower self-concept, lower socioeconomic status, poorer interpersonal relations, and chronic health conditions (P < .01). CONCLUSIONS: Among emerging adults, trajectories of depressive symptoms do not trend upward or downward, and variables associated with identified trajectories demonstrated dose-response effects that agreed with vulnerability-stress theories of depression. PMID- 26378841 TI - "We're Part of the Solution": Evolution of the Food and Beverage Industry's Framing of Obesity Concerns Between 2000 and 2012. AB - We investigated how industry claim-makers countered concerns about obesity and other nutrition-related diseases in newspaper coverage from 2000, the year before the US Surgeon General's Call to Action on obesity, through 2012. We found that the food and beverage industry evolved in its response. The defense arguments were made by trade associations, industry-funded nonprofit groups, and individual companies representing the packaged food industry, restaurants, and the nonalcoholic beverage industry. Individual companies used the news primarily to promote voluntary self-regulation, whereas trade associations and industry supported nonprofit groups directly attacked potential government regulations. There was, however, a shift away from framing obesity as a personal issue toward an overall message that the food and beverage industry wants to be "part of the solution" to the public health crisis. PMID- 26378842 TI - Incarceration and Current Tobacco Smoking Among Black and Caribbean Black Americans in the National Survey of American Life. AB - OBJECTIVES: We examined the relationship between having a history of incarceration and being a current smoker using a national sample of noninstitutionalized Black adults living in the United States. METHODS: With data from the National Survey of American Life collected between February 2001 and March 2003, we calculated individual propensity scores for having a history of incarceration. To examine the relationship between prior incarceration and current smoking status, we ran gender-specific propensity-matched fitted logistic regression models. RESULTS: A history of incarceration was consistently and independently associated with a higher risk of current tobacco smoking in men and women. Formerly incarcerated Black men had 1.77 times the risk of being a current tobacco smoker than did their counterparts without a history of incarceration (95% confidence interval [CI] = 1.20, 2.61) in the propensity score-matched sample. The results were similar among Black women (prevalence ratio = 1.61; 95% CI = 1.00, 2.57). CONCLUSIONS: Mass incarceration likely contributes to the prevalence of smoking among US Blacks. Future research should explore whether the exclusion of institutionalized populations in national statistics obscures Black White disparities in tobacco smoking. PMID- 26378843 TI - Adherence to Mammography Screening Guidelines Among Transgender Persons and Sexual Minority Women. AB - We used retrospective (2012-2013) chart review to examine breast cancer screening among transgender persons and sexual minority women (n = 1263) attending an urban community health center in Massachusetts. Transgender were less likely than cisgender patients and bisexuals were less likely than heterosexuals and lesbians to adhere to mammography screening guidelines (respectively, adjusted odds ratios = 0.53 and 0.56; 95% confidence intervals = 0.31, 0.91 and 0.34, 0.92) after adjustment for sociodemographics. Enhanced cancer prevention outreach is needed among gender and sexual minorities. PMID- 26378844 TI - Implications of the Supplemental Nutrition Assistance Program Tax Exemption on Sugar-Sweetened Beverage Taxes. AB - US state and local governments are debating sugar-sweetened beverage excise taxes to support public health. A related issue is whether such taxes would apply to beverage purchases made by Supplemental Nutrition Assistance Program (SNAP) participants. Federal law proscribes states from collecting excise taxes on SNAP purchases, but the law is confined to taxes at the point of sale. I provide legal analysis and recommendations for policymakers to enact taxes that are not subject to the SNAP tax exemption to potentially deter consumption by all consumers. PMID- 26378845 TI - The Perceived Consequences of Gold Mining in Postwar El Salvador: A Qualitative Study. AB - OBJECTIVES: We investigated themes related to the health and environmental impacts of gold mining in El Salvador. METHODS: Over a 1-month period in 2013, we conducted focus groups (n = 32 participants in total) and individual semistructured interviews (n = 11) with community leaders until we achieved thematic saturation. Data collection took place in 4 departments throughout the country. We used a combination of criterion-purposive and snowballing sampling techniques to identify participants. RESULTS: Multiple themes emerged: (1) the fallacy of economic development; (2) critique of mining activities; (3) the creation of mining-related violence, with parallels to El Salvador's civil war; and (4) solutions and alternatives to mining activity. Solutions involved the creation of cooperative microenterprises for sustainable economic growth, political empowerment within communities, and development of local participatory democracies. CONCLUSIONS: Gold mining in El Salvador is perceived as a significant environmental and public health threat. Local solutions may be applicable broadly. PMID- 26378846 TI - A Qualitative Inquiry About Pruno, an Illicit Alcoholic Beverage Linked to Botulism Outbreaks in United States Prisons. AB - OBJECTIVES: Since 2011, 3 outbreaks of botulism in US prisons have been attributed to pruno, which is an alcoholic beverage made by inmates. Following 1 outbreak, we conducted a qualitative inquiry to understand pruno brewing and its social context to inform outbreak prevention measures. METHODS: We interviewed staff, inmates, and parolees from 1 prison about pruno production methods, the social aspects of pruno, and strategies for communicating the association between botulism and pruno. RESULTS: Twenty-seven inmates and parolees and 13 staff completed interviews. Pruno is fermented from water, fruit, sugar, and miscellaneous ingredients. Knowledge of pruno making was widespread among inmates; staff were familiar with only the most common ingredients and supplies inmates described. Staff and inmates described inconsistent consequences for pruno possession and suggested using graphic health messages from organizations external to the prison to communicate the risk of botulism from pruno. CONCLUSIONS: Pruno making was frequent in this prison. Improved staff recognition of pruno ingredients and supplies might improve detection of brewing activities in this and other prisons. Consistent consequences and clear messages about the association between pruno and botulism might prevent outbreaks. PMID- 26378847 TI - Intergenerational Patterns of Smoking and Nicotine Dependence Among US Adolescents. AB - OBJECTIVES: We examined associations between parental and adolescent smoking and nicotine dependence in the United States. METHODS: We used data from the 2004 to 2012 National Survey on Drug Use and Health, which ascertained smoking behaviors of 1 parent and 1 adolescent aged 12 to 17 years in 35 000 dyads. We estimated associations between parental and adolescent smoking behaviors, adjusted for covariates. RESULTS: Parental current dependence was strongly associated with adolescents' lifetime smoking (adjusted odds ratio [AOR] = 2.96; 95% confidence interval [CI] = 2.47, 3.55), whereas parental current nondependent smoking (AOR = 2.26; 95% CI = 1.92, 2.67) and former smoking (AOR = 1.51; 95% CI = 1.31, 1.75) were less strongly associated. Only parental nicotine dependence was associated with adolescent nicotine dependence (AOR = 1.66; 95% CI = 1.00, 2.74). Associations between parental and adolescent smoking did not differ by race/ethnicity. Parents' education, marital status, and parenting and adolescents' mental health, beliefs about smoking, perception of schoolmates' smoking, and other substance use predicted adolescent smoking and dependence. CONCLUSIONS: Reducing parental smoking would reduce adolescent smoking. Prevention efforts should encourage parental smoking cessation, improve parenting, address adolescent mental health, and reinforce adolescents' negative beliefs about smoking. PMID- 26378849 TI - Overdose Epidemic, Prescription Monitoring Programs, and Public Health: A Review of State Laws. AB - Prescription monitoring programs (PMPs), state-level databases that collect patient-specific prescription information at the time medications are dispensed, have been suggested as tools to address the overdose epidemic. We reviewed all laws in the United States (n = 25) that articulated the purposes PMPs are intended to serve. Attributes related to reducing abuse, misuse, and diversion of prescription medications appeared most commonly. Only 5 purpose statements mentioned the promotion of public health as goals of the PMP, and only 3 listed improving health care. None listed overdose prevention as a goal of the PMP. PMID- 26378848 TI - Multinational Alcohol Market Development and Public Health: Diageo in India. AB - Alcohol is a risk factor for communicable and noncommunicable diseases, and alcohol consumption is rising steadily in India. The growth of multinational alcohol corporations, such as Diageo, contributes to India's changing alcohol environment. We provide a brief history of India's alcohol regulation for context and examine Diageo's strategies for expansion in India in 2013 and 2014. Diageo is attracted to India's younger generation, women, and emerging middle class for growth opportunities. Components of Diageo's responsibility strategy conflict with evidence-based public health recommendations for reducing harmful alcohol consumption. Diageo's strategies for achieving market dominance in India are at odds with public health evidence. We conclude with recommendations for protecting public health in emerging markets. PMID- 26378850 TI - Effects of Racial Prejudice on the Health of Communities: A Multilevel Survival Analysis. AB - OBJECTIVES: We examined whether and how racial prejudice at both the individual and community levels contributes to mortality risk among majority as well as minority group members. METHODS: We used data on racial attitudes from the General Social Survey (1993-2002) prospectively linked to mortality data from the National Death Index through 2008. RESULTS: Whites and Blacks living in communities with higher levels of racial prejudice were at an elevated risk of mortality, independent of individual and community sociodemographic characteristics and individually held racist beliefs (odds ratio = 1.24; 95% confidence interval = 1.04, 1.49). Living in a highly prejudiced community had similar harmful effects among both Blacks and Whites. Furthermore, the interaction observed between individual- and community-level racial prejudice indicated that respondents with higher levels of racial prejudice had lower survival rates if they lived in communities with low degrees of racial prejudice. Community-level social capital explained the relationship between community racial prejudice and mortality. CONCLUSIONS: Community-level racial prejudice may disrupt social capital, and reduced social capital is associated with increased mortality risk among both Whites and Blacks. Our results contribute to an emerging body of literature documenting the negative consequences of prejudice for population health. PMID- 26378851 TI - Type 2 Diabetes and Anxiety Symptoms Among Women in New Delhi, India. AB - OBJECTIVES: We explored the relationship between mental health and type 2 diabetes among women in New Delhi, India, in 2011. METHODS: We recruited a convenience sample of 184 diabetic women from 10 public and private clinics. They completed a finger-stick blood test and a questionnaire assessing demographic characteristics, depression and anxiety symptoms, and diabetes-related disabilities restricting their performance of daily tasks. A subsample of 30 women participated in follow-up qualitative interviews at their homes. RESULTS: More than one quarter of our sample of diabetic women reported high levels of anxiety symptoms, whereas 18% reported high levels of depression symptoms. Anxiety symptoms were patterned according to recency of diabetes diagnosis, with 40% of women diagnosed less than 2 years before their interview reporting high anxiety symptom levels, as opposed to 23% of women diagnosed more than 2 years in the past. Depression and anxiety scores differed with respect to their relationship to recency of diagnosis, number of children, blood glucose level, and functional disabilities restricting performance of daily tasks. CONCLUSIONS: Screening for anxiety among people with diabetes has been overlooked in the past. Anxiety appears more prevalent than depression, especially during the first 2 years of the disease. PMID- 26378852 TI - Workplace Bullying and Suicidal Ideation: A 3-Wave Longitudinal Norwegian Study. AB - OBJECTIVES: We examined whether victimization from bullying is related to an increased risk of suicidal ideation over time and whether suicidal ideation is related to subsequent bullying. METHODS: In a longitudinal study (2005-2010), we used well-established single-item measures to assess victimization from bullying and suicidal ideation. We used latent Markov models to determine forward and reverse relationships between variables at 3 time points with 2 or 3 years between the measurement points among a randomized nationwide sample of 1846 employees in Norway. RESULTS: Victimization from bullying was associated with subsequent suicidal ideation (odds ratio = 2.05; 95% confidence interval = 1.08, 3.89). Suicidal ideation at baseline was not related to subsequent victimization from workplace bullying. CONCLUSIONS: Workplace bullying may be a precursor to suicidal ideation, whereas suicidal ideation seems to have no impact on subsequent risk of being bullied. Regulations against bullying should be integrated into work-related legislation and public health policies. PMID- 26378853 TI - News Media Framing of New York City's Sugar-Sweetened Beverage Portion-Size Cap. AB - OBJECTIVES: We assessed news media framing of New York City's proposed regulation to prohibit the sale of sugar-sweetened beverages greater than 16 ounces. METHODS: We conducted a quantitative content analysis of print and television news from within and outside New York City media markets. We examined support for and opposition to the portion-size cap in the news coverage from its May 31, 2012, proposal through the appellate court ruling on July 31, 2013. RESULTS: News coverage corresponded to key events in the policy's evolution. Although most stories mentioned obesity as a problem, a larger proportion used opposing frames (84%) than pro-policy frames (36%). Mention of pro-policy frames shifted toward the policy's effect on special populations. The debate's most prominent frame was the opposing frame that the policy was beyond the government's role (69%). CONCLUSIONS: News coverage within and outside the New York City media market was more likely to mention arguments in opposition to than in support of the portion size cap. Understanding how the news media framed this issue provides important insights for advocates interested in advancing similar measures in other jurisdictions. PMID- 26378854 TI - HIV Testing and HIV Service Delivery to Populations at High Risk Attending Sexually Transmitted Disease Clinics in the United States, 2011-2013. AB - OBJECTIVES: We evaluated HIV testing and service delivery in Centers for Disease Control and Prevention (CDC)-funded sexually transmitted disease (STD) clinics. METHODS: We assessed HIV testing, HIV positivity, receipt of HIV test results, linkage to medical care, and referral services from 61 health department jurisdictions from 2011 to 2013. RESULTS: In 2013, 18.6% (621 010) of all CDC funded HIV-testing events were conducted in STD clinics, and 0.8% were newly identified as HIV-positive. In addition, 27.3% of all newly identified HIV positive persons and 30.1% of all newly identified HIV-positive men who have sex with men were identified in STD clinics. Linkage to care within any time frame was 63.8%, and linkage within 90 days was 55.3%. Although there was a decrease in first-time HIV testers in STD clinics from 2011 to 2013, identification of new positives increased. CONCLUSIONS: Although linkage to care and referral to partner services could be improved, STD clinics appear successful at serving populations disproportionately affected by HIV. These clinics may reach persons who may not otherwise seek HIV testing or medical services and provide an avenue for service provision to these populations. PMID- 26378855 TI - Hiv And Sexually Transmitted Infections Among Youths: A Brazilian Perception. PMID- 26378857 TI - Fildes et al. Respond. PMID- 26378856 TI - Maternal Allostatic Load, Caretaking Behaviors, and Child Dental Caries Experience: A Cross-Sectional Evaluation of Linked Mother-Child Data From the Third National Health and Nutrition Examination Survey. AB - OBJECTIVES: We evaluated the associations between chronic maternal stress measured by allostatic load (AL), maternal caretaking behaviors, and child dental caries experience. We also assessed the role of socioeconomic status in these associations. METHODS: We used data from the Third National Health and Nutrition Examination Survey (1988-1994). We included children aged 2 to 6 years who linked to a maternal record (n = 716 maternal-child pairs). The main exposure was maternal AL index (0, 1, or >= 2). The primary outcome of interest was child dental caries experience (none or any). We evaluated the association between maternal AL and (1) maternal caretaking behaviors, and (2) child caries status and the role of socioeconomic status in these relationships. RESULTS: Children of mothers with an AL index of at least 2 were significantly more likely to have not been breastfed and to have dental caries than were children of mothers with a normal AL before adjusting for measures of socioeconomic status. CONCLUSIONS: Maternal chronic stress, indicated by elevation in markers of AL, has an important role in child caretaking behaviors and in children's oral health. PMID- 26378858 TI - Spousal Violence in 5 Transitional Countries: A Population-Based Multilevel Analysis of Individual and Contextual Factors. AB - OBJECTIVES: I examined the individual- and community-level factors associated with spousal violence in post-Soviet countries. METHODS: I used population-based data from the Demographic and Health Survey conducted between 2005 and 2012. My sample included currently married women of reproductive age (n = 3932 in Azerbaijan, n = 4053 in Moldova, n = 1932 in Ukraine, n = 4361 in Kyrgyzstan, and n = 4093 in Tajikistan). I selected respondents using stratified multistage cluster sampling. Because of the nested structure of the data, multilevel logistic regressions for survey data were fitted to examine factors associated with spousal violence in the last 12 months. RESULTS: Partner's problem drinking was the strongest risk factor associated with spousal violence in all 5 countries. In Moldova, Ukraine, and Kyrgyzstan, women with greater financial power than their spouses were more likely to experience violence. Effects of community economic deprivation and of empowerment status of women in the community on spousal violence differed across countries. Women living in communities with a high tolerance of violence faced a higher risk of spousal violence in Moldova and Ukraine. In more traditional countries (Azerbaijan, Kyrgyzstan, and Tajikistan), spousal violence was lower in conservative communities with patriarchal gender beliefs or higher financial dependency on husbands. CONCLUSIONS: My findings underscore the importance of examining individual risk factors in the context of community-level factors and developing individual- and community-level interventions. PMID- 26378859 TI - Practice-Based Research Priorities for Palliative Care: Results From a Research to-Practice Consensus Workshop. AB - We employed the research-to-practice consensus workshop (RTP; workshops held in New York City and Tompkins County, New York, in 2013) model to merge researcher and practitioner views of translational research priorities in palliative care. In the RTP approach, a diverse group of frontline providers generates a research agenda for palliative care in collaboration with researchers. We have presented the major workshop recommendations and contrasted the practice-based research priorities with those of previous consensus efforts. We uncovered notable differences and found that the RTP model can produce unique insights into research priorities. Integrating practitioner-identified needs into research priorities for palliative care can contribute to addressing palliative care more effectively as a public health issue. PMID- 26378860 TI - The Two Ways of Assessing Heat-Related Mortality and Vulnerability. PMID- 26378861 TI - Beverage Marketing as a Public Health Policy Target. PMID- 26378862 TI - Implications of Repealing the Cuban Embargo for US Medicine and Public Health. PMID- 26378863 TI - How to Identify Success Among Networks That Promote Active Living. AB - OBJECTIVES: We evaluated organization- and network-level factors that influence organizations' perceived success. This is important for managing interorganizational networks, which can mobilize communities to address complex health issues such as physical activity, and for achieving change. METHODS: In 2011, we used structured interview and network survey data from 22 states in the United States to estimate multilevel random-intercept models to understand organization- and network-level factors that explain perceived network success. RESULTS: A total of 53 of 59 "whole networks" met the criteria for inclusion in the analysis (89.8%). Coordinators identified 559 organizations, with 3 to 12 organizations from each network taking the online survey (response rate = 69.7%; range = 33%-100%). Occupying a leadership position (P < .01), the amount of time with the network (P < .05), and support from community leaders (P < .05) emerged as correlates of perceived success. CONCLUSIONS: Organizations' perceptions of success can influence decisions about continuing involvement and investment in networks designed to promote environment and policy change for active living. Understanding these factors can help leaders manage complex networks that involve diverse memberships, varied interests, and competing community-level priorities. PMID- 26378864 TI - E-cigarettes are losing ground among smokers and non-smokers. PMID- 26378865 TI - Novel Carbon Nanotube/Cellulose Composite Fibers As Multifunctional Materials. AB - Electroconductive fibers composed of cellulose and carbon nanotubes (CNTs) were spun using aqueous alkaline/urea solution. The microstructure and physical properties of the resulting fibers were investigated by scanning electron microscopy, Raman microscopy, wide-angle X-ray diffraction, tensile tests, and electrical resistance measurements. We found that these flexible composite fibers have sufficient mechanical properties and good electrical conductivity, with volume resistivities in the range of about 230-1 Ohm cm for 2-8 wt % CNT loading. The multifunctional sensing behavior of these fibers to tensile strain, temperature, environmental humidity, and liquid water was investigated comprehensively. The results show that these novel CNT/cellulose composite fibers have impressive multifunctional sensing abilities and are promising to be used as wearable electronics and for the design of various smart materials. PMID- 26378867 TI - Association between air pollution and benign prostatic hyperplasia: An ecological study. AB - Benign prostate hyperplasia (BPH) is a prevalent medical condition; however, little is known about the effect of environmental factors. Therefore, we conducted surveys to examine the association between air pollution and the risk of BPH in South Korea between May 2010 and April 2013, yielding data for 1,734 men. Air pollution information was obtained from the National Air Pollutants Emission 2010 report. Logistic regression analyses were conducted after adjusting for potential confounders. The International Prostate Symptom Score significantly increased with increasing per capita air pollutant emissions. The risk of BPH increased as the overall concentration of air pollutants increased (odds ratio [OR], 2.23; 95% confidence interval [CI], 1.55-3.21). In particular, nitrogen oxides (OR, 1.73; 95% CI, 1.25-2.39) and sulfur oxides (OR, 2.02; 95% CI, 1.42 2.88) showed a dose-dependent association. Our findings support a positive association between the risk of BPH and air pollution. PMID- 26378866 TI - Safety and tolerability evaluation of the use of Montanide ISATM51 as vaccine adjuvant: A systematic review. AB - Montanide ISATM51 (ISA 51) is a vaccine adjuvant which has been tested in therapeutic and prophylactic vaccine trials. The aim of this review is to present a comprehensive examination of the safety and tolerability of ISA 51 containing vaccines. A systematic literature search was conducted in PubMed, EMBASE and clinicaltrials.gov . Eligible studies were categorized into: (A) uncontrolled studies with non-healthy subjects, (B) controlled studies with non-healthy subjects, and (C) controlled studies with healthy subjects. Reported adverse events (AEs) were assessed. 91 studies were included in our review. Generally observed AEs included injection site reaction; injection site pain; myalgia; headache; gastro-intestinal disorders; fatigue and fever - regardless of the administration route and subject characteristic. Specific AEs, e.g. injection site reactions and rash, were more frequently reported from subjects receiving ISA 51-adjuvanted vaccines than from subjects receiving antigen or ISA 51 only. The reported AEs were mainly mild to moderate in intensity. Serious AEs (SAEs) were reported in 27% of the uncontrolled trials and 2 trials conducted with healthy subjects. Notably, 2 other trials conducted with healthy subjects were stopped due to unacceptable AEs. Some studies indicate that the mixing procedure of antigen and adjuvant might influence the occurrence of AEs. Reports on SAEs and premature termination of 2 trials advise caution when using ISA 51. Yet, AEs might be preventable by proper mixing of vaccine and adjuvant to a stable emulsion. Trials including an active control group are needed for a fair evaluation of adjuvant safety. PMID- 26378868 TI - Development of a Transcatheter Tricuspid Valve Prosthesis Through Steps of Iterative Optimization and Finite Element Analysis. AB - The development of a transcatheter tricuspid valve prosthesis for the treatment of tricuspid regurgitation (TR) is presented. The design process involves an iterative development method based on computed tomography data and different steps of finite element analysis (FEA). The enhanced design consists of two self expandable stents, one is placed inside the superior vena cava (SVC) for primary device anchoring, the second lies inside the tricuspid valve annulus (TVA). Both stents are connected by flexible connecting struts (CS) to anchor the TVA-stent in the orthotopic position. The iterative development method includes the expansion and crimping of the stents and CS with FEA. Leaflet performance and leaflet-stent interaction were studied by applying the physiologic pressure cycle of the right heart onto the leaflet surfaces. A previously implemented nitinol material model and a new porcine pericardium material model derived from uniaxial tensile tests were used. Maximum strains/stresses were approx. 6.8% for the nitinol parts and 2.9 MPa for the leaflets. Stent displacement because of leaflet movement was <=1.8 mm at the commissures and the coaptation height was 1.6-3 mm. This led to an overall good performance of the prosthesis. An anatomic study showed a good anatomic fit of the device inside the human right heart. PMID- 26378869 TI - Bioremediation potential of a highly mercury resistant bacterial strain Sphingobium SA2 isolated from contaminated soil. AB - A mercury resistant bacterial strain, SA2, was isolated from soil contaminated with mercury. The 16S rRNA gene sequence of this isolate showed 99% sequence similarity to the genera Sphingobium and Sphingomonas of alpha-proteobacteria group. However, the isolate formed a distinct phyletic line with the genus Sphingobium suggesting the strain belongs to Sphingobium sp. Toxicity studies indicated resistance to high levels of mercury with estimated EC50 values 4.5 mg L(-1) and 44.15 mg L(-1) and MIC values 5.1 mg L(-1) and 48.48 mg L(-1) in minimal and rich media, respectively. The strain SA2 was able to volatilize mercury by producing mercuric reductase enzyme which makes it potential candidate for remediating mercury. ICP-QQQ-MS analysis of Hg supplemented culture solutions confirmed that almost 79% mercury in the culture suspension was volatilized in 6 h. A very small amount of mercury was observed to accumulate in cell pellets which was also evident according to ESEM-EDX analysis. The mercuric reductase gene merA was amplified and sequenced. The deduced amino acid sequence demonstrated sequence homology with alpha-proteobacteria and Ascomycota group. PMID- 26378871 TI - Risk assessment of Cd polluted paddy soils in the industrial and township areas in Hunan, Southern China. AB - Cadmium (Cd) contamination in rice in Youxian, Hunan, China is a major environmental health concern. In order to reveal the Cd contamination in rice and paddy soils and the health risks to the population consuming the local rice grain, field surveys were conducted in eight towns in Youxian, China. The Cd contents of paddy soils averaged 0.228-1.91 mg kg(-1), 90% exceeding the allowable limit of 0.3 mg kg(-1) stipulated by the China Soil Environmental Quality Standards. Low average pH values (for air dried oxidized soils) ranging from 4.98 to 6.02 in paddy soil were also found. More than seventy percent (39 of 53) of the grain samples exceeded the maximum safe concentration of Cd, 0.2 mg kg(-1) on a dry weight basis. Considering the high consumption of local rice (339 g capita(-1) DW d(-1)) and Cd levels measured, dietary ingestion of 78% of the sampled rice grains would have adverse health risks because the intake exposure of Cd was greater than the JECFA recommended exposures, 0.8 ug Cd BW kg(-1) day( 1) or 25 ug Cd BW kg(-1) month(-1). PMID- 26378870 TI - Development of a 4-NQO toxic equivalency factor (TEF) approach to enable a preliminary risk assessment of unknown genotoxic compounds detected by the Ames II test in UV/H2O2 water treatment samples. AB - An approach to enable a preliminary risk assessment of unknown genotoxic compounds formed by MP UV/H2O2 treatment of nitrate rich water, is described. Since the identity and concentration of specific genotoxic compounds is not established yet, a compound specific risk assessment cannot be performed. This limitation is circumvented by introducing a toxic equivalency factor, converting the concentration of unknown genotoxic compounds expressed by an Ames II test response into equivalent concentrations of 4-nitroquinoline oxide (4-NQO), to enable a preliminary risk assessment. Based on the obtained 4-NQO equivalent concentrations for the tested water samples and 4-NQO carcinogenicity data, an indication of the associated risk of the by MP UV/H2O2 treatment produced nitrated genotoxic compounds is obtained via the margin of exposure (MOE) approach. Based on a carcinogen study by Tang et al. (2004), a body weight of 70 kg and a drinking water consumption of 2 L per day, the 4-NQO equivalent concentration should not exceed 80 ng/L associated with a negligible risk. Application of this approach on samples from MP UV/H2O2 treated water of a full scale drinking water production facility, a 4-NQO equivalent concentration of 107 ng/L was established. These results indicate a safety concern in case this water would be distributed as drinking water without further post treatment. PMID- 26378872 TI - Impact of nanoscale zero valent iron on bacteria is growth phase dependent. AB - The toxic effect of nanoscale zero valent iron (nZVI) particles on bacteria from different growth phases was studied. Four bacterial strains namely Escherichia coli strains JM109 and BW25113, and Pseudomonas putida strains KT2440 and F1 were experimented. The growth curves of these strains were determined. Bacterial cells were harvested based on the predetermined time points, and exposed to nZVI. Cell viability was determined by the plate count method. Bacterial cells in lag and stationary phases showed higher resistance to nZVI for all four bacterial strains, whereas cells in exponential and decline phases were less resistant to nZVI and were rapidly inactivated when exposed to nZVI. Bacterial inactivation increased with the concentration of nZVI. Furthermore, less than 14% bacterial inactivation was observed when bacterial cells were exposed to the filtrate of nZVI suspension suggesting that the physical interaction between nZVI and cell is necessary for bacterial inactivation. PMID- 26378873 TI - Ulnar nerve cutaneous distribution in the palm: Application to surgery of the hand. AB - The ulnar nerve (UN) was classically described as supplying most of the intrinsic muscles of the hand, and the cutaneous innervation of the ulnar one and half digits, by dividing into superficial sensory and deep motor branches in Guyon's canal. Variations of this pattern have been reported in the literature. This study investigated the cutaneous distribution of the UN in the palm following the dissection of 144 cadaveric hands. The UN was examined and the distances from branching points of the superficial branch to the proximal edge of the pisiform were measured. The UN bifurcated (80.4%) into one deep trunk and one superficial trunk, which further divided distally into the proper digital (PDN) and common digital (CDN) nerves or trifurcated (19.6%) into one deep trunk, a PDN and a CDN in Guyon's canal. It received fibers from the median nerve in four cases and from the dorsal branch of the UN in six cases. A classification scheme based on the nerves contributing to the sensory innervation of the ulnar side of the palm was suggested. Understanding the cutaneous distribution of the UN in the palm and appreciating possible communicating branches can help clinicians to assess hand pathologies better and avoid injuries during surgical interventions. PMID- 26378874 TI - Hierarchical Error Representation: A Computational Model of Anterior Cingulate and Dorsolateral Prefrontal Cortex. AB - Anterior cingulate and dorsolateral prefrontal cortex (ACC and dlPFC, respectively) are core components of the cognitive control network. Activation of these regions is routinely observed in tasks that involve monitoring the external environment and maintaining information in order to generate appropriate responses. Despite the ubiquity of studies reporting coactivation of these two regions, a consensus on how they interact to support cognitive control has yet to emerge. In this letter, we present a new hypothesis and computational model of ACC and dlPFC. The error representation hypothesis states that multidimensional error signals generated by ACC in response to surprising outcomes are used to train representations of expected error in dlPFC, which are then associated with relevant task stimuli. Error representations maintained in dlPFC are in turn used to modulate predictive activity in ACC in order to generate better estimates of the likely outcomes of actions. We formalize the error representation hypothesis in a new computational model based on our previous model of ACC. The hierarchical error representation (HER) model of ACC/dlPFC suggests a mechanism by which hierarchically organized layers within ACC and dlPFC interact in order to solve sophisticated cognitive tasks. In a series of simulations, we demonstrate the ability of the HER model to autonomously learn to perform structured tasks in a manner comparable to human performance, and we show that the HER model outperforms current deep learning networks by an order of magnitude. PMID- 26378876 TI - Bayesian Feature Selection with Strongly Regularizing Priors Maps to the Ising Model. AB - Identifying small subsets of features that are relevant for prediction and classification tasks is a central problem in machine learning and statistics. The feature selection task is especially important, and computationally difficult, for modern data sets where the number of features can be comparable to or even exceed the number of samples. Here, we show that feature selection with Bayesian inference takes a universal form and reduces to calculating the magnetizations of an Ising model under some mild conditions. Our results exploit the observation that the evidence takes a universal form for strongly regularizing priors--priors that have a large effect on the posterior probability even in the infinite data limit. We derive explicit expressions for feature selection for generalized linear models, a large class of statistical techniques that includes linear and logistic regression. We illustrate the power of our approach by analyzing feature selection in a logistic regression-based classifier trained to distinguish between the letters B and D in the notMNIST data set. PMID- 26378875 TI - Visual Decisions in the Presence of Measurement and Stimulus Correlations. AB - Humans and other animals base their decisions on noisy sensory input. Much work has been devoted to understanding the computations that underlie such decisions. The problem has been studied in a variety of tasks and with stimuli of differing complexity. However, how the statistical structure of stimuli, along with perceptual measurement noise, affects perceptual judgments is not well understood. Here we examine how correlations between the components of a stimulus stimulus correlations-together with correlations in sensory noise, affect decision making. As an example, we consider the task of detecting the presence of a single or multiple targets among distractors. We assume that both the distractors and the observer's measurements of the stimuli are correlated. The computations of an optimal observer in this task are nontrivial yet can be analyzed and understood intuitively. We find that when distractors are strongly correlated, measurement correlations can have a strong impact on performance. When distractor correlations are weak, measurement correlations have little impact unless the number of stimuli is large. Correlations in neural responses to structured stimuli can therefore have a strong impact on perceptual judgments. PMID- 26378877 TI - A Novel Parameter Estimation Method for Boltzmann Machines. AB - We propose a novel estimator for a specific class of probabilistic models on discrete spaces such as the Boltzmann machine. The proposed estimator is derived from minimization of a convex risk function and can be constructed without calculating the normalization constant, whose computational cost is exponential order. We investigate statistical properties of the proposed estimator such as consistency and asymptotic normality in the framework of the estimating function. Small experiments show that the proposed estimator can attain comparable performance to the maximum likelihood expectation at a much lower computational cost and is applicable to high-dimensional data. PMID- 26378878 TI - Bandit-Based Task Assignment for Heterogeneous Crowdsourcing. AB - We consider a task assignment problem in crowdsourcing, which is aimed at collecting as many reliable labels as possible within a limited budget. A challenge in this scenario is how to cope with the diversity of tasks and the task-dependent reliability of workers; for example, a worker may be good at recognizing the names of sports teams but not be familiar with cosmetics brands. We refer to this practical setting as heterogeneous crowdsourcing. In this letter, we propose a contextual bandit formulation for task assignment in heterogeneous crowdsourcing that is able to deal with the exploration exploitation trade-off in worker selection. We also theoretically investigate the regret bounds for the proposed method and demonstrate its practical usefulness experimentally. PMID- 26378879 TI - STICK: Spike Time Interval Computational Kernel, a Framework for General Purpose Computation Using Neurons, Precise Timing, Delays, and Synchrony. AB - There has been significant research over the past two decades in developing new platforms for spiking neural computation. Current neural computers are primarily developed to mimic biology. They use neural networks, which can be trained to perform specific tasks to mainly solve pattern recognition problems. These machines can do more than simulate biology; they allow us to rethink our current paradigm of computation. The ultimate goal is to develop brain-inspired general purpose computation architectures that can breach the current bottleneck introduced by the von Neumann architecture. This work proposes a new framework for such a machine. We show that the use of neuron-like units with precise timing representation, synaptic diversity, and temporal delays allows us to set a complete, scalable compact computation framework. The framework provides both linear and nonlinear operations, allowing us to represent and solve any function. We show usability in solving real use cases from simple differential equations to sets of nonlinear differential equations leading to chaotic attractors. PMID- 26378880 TI - STOP-Bang Questionnaire: A Practical Approach to Screen for Obstructive Sleep Apnea. AB - There exists a high prevalence of OSA in the general population, a great proportion of which remains undiagnosed. The snoring, tiredness, observed apnea, high BP, BMI, age, neck circumference, and male gender (STOP-Bang) questionnaire was specifically developed to meet the need for a reliable, concise, and easy-to use screening tool. It consists of eight dichotomous (yes/no) items related to the clinical features of sleep apnea. The total score ranges from 0 to 8. Patients can be classified for OSA risk based on their respective scores. The sensitivity of STOP-Bang score >= 3 to detect moderate to severe OSA (apnea hypopnea index [AHI] > 15) and severe OSA (AHI > 30) is 93% and 100%, respectively. Corresponding negative predictive values are 90% and 100%. As the STOP-Bang score increases from 0 to 2 up to 7 to 8, the probability of moderate to severe OSA increases from 18% to 60%, and the probability of severe OSA rises from 4% to 38%. Patients with a STOP-Bang score of 0 to 2 can be classified as low risk for moderate to severe OSA whereas those with a score of 5 to 8 can be classified as high risk for moderate to severe OSA. In patients whose STOP-Bang scores are in the midrange (3 or 4), further criteria are required for classification. For example, a STOP-Bang score of >= 2 plus a BMI > 35 kg/m(2) would classify that patient as having a high risk for moderate to severe OSA. In this way, patients can be stratified for OSA risk according to their STOP-Bang scores. PMID- 26378881 TI - The Role of Body Image in the Relationship Between Internet Use and Bulimic Symptoms: Three Theoretical Frameworks. AB - Exposure to traditional media has been associated with bulimic symptoms. However, to date, little is known regarding the effects of Internet exposure. The aim of this study was to explore the relationships between Internet use and bulimic symptoms within the competing frameworks of sociocultural, impression management, and self-objectification theory. A sample of 289 French women aged 18-25 years completed an online questionnaire assessing bulimic symptoms, body dissatisfaction, body image avoidance, self-surveillance, body shame, and weekly Internet use. Bootstrapping analyses revealed that body shame and body image avoidance mediated the effect of weekly Internet use on bulimic symptoms. Furthermore, when entered into a multiple mediation analysis, these two variables provided independent mediation pathways of equal magnitude. The findings support the usefulness of both the self-objectification and impression management frameworks for investigating the relationship between Internet use and bulimic symptoms. Longitudinal research would help to clarify these pathways further. PMID- 26378882 TI - Discovery and Optimization of a Series of Pyrimidine-Based Phosphodiesterase 10A (PDE10A) Inhibitors through Fragment Screening, Structure-Based Design, and Parallel Synthesis. AB - Screening of a fragment library for PDE10A inhibitors identified a low molecular weight pyrimidine hit with PDE10A Ki of 8700 nM and LE of 0.59. Initial optimization by catalog followed by iterative parallel synthesis guided by X-ray cocrystal structures resulted in rapid potency improvements with minimal loss of ligand efficiency. Compound 15 h, with PDE10A Ki of 8.2 pM, LE of 0.49, and >5000 fold selectivity over other PDEs, fully attenuates MK-801-induced hyperlocomotor activity after ip dosing. PMID- 26378883 TI - Ocular Surface Squamous Neoplasia: From Blue Skies to Blue Dyes--We Still Need Our Ophthalmic Pathologists. PMID- 26378885 TI - Contrasting actions of a convulsant barbiturate and its anticonvulsant enantiomer on the alpha1 beta3 gamma2L GABAA receptor account for their in vivo effects. AB - KEY POINTS: Most barbiturates are anaesthetics but unexpectedly a few are convulsants whose mechanism of action is poorly understood. We synthesized and characterized a novel pair of chiral barbiturates that are capable of photolabelling their binding sites on GABAA receptors. In mice the S-enantiomer is a convulsant, but the R-enantiomer is an anticonvulsant. The convulsant S enantiomer binds solely at an inhibitory site. It is both an open state inhibitor and a resting state inhibitor. Its action is pH independent, suggesting the pyrimidine ring plays little part in binding. The inhibitory site is not enantioselective because the R-enantiomer inhibits with equal affinity. In contrast, only the anticonvulsant R-enantiomer binds to the enhancing site on open channels, causing them to stay open longer. The enhancing site is enantioselective. The in vivo actions of the convulsant S-enantiomer are accounted for by its interactions with GABAA receptors. ABSTRACT: Most barbiturates are anaesthetics but a few unexpectedly are convulsants. We recently located the anaesthetic sites on GABAA receptors (GABAA Rs) by photolabelling with an anaesthetic barbiturate. To apply the same strategy to locate the convulsant sites requires the creation and mechanistic characterization of a suitable agent. We synthesized enantiomers of a novel, photoactivable barbiturate, 1-methyl-5-propyly-5-(m-trifluoromethyldiazirinyl) phenyl barbituric acid (mTFD-MPPB). In mice, S-mTFD-MPPB acted as a convulsant, whereas R-mTFD-MPPB acted as an anticonvulsant. Using patch clamp electrophysiology and fast solution exchange on recombinant human alpha1 beta3 gamma2L GABAA Rs expressed in HEK cells, we found that S-mTFD-MPPB inhibited GABA-induced currents, whereas R-mTFD MPPB enhanced them. S-mTFD-MPPB caused inhibition by binding to either of two inhibitory sites on open channels with bimolecular kinetics. It also inhibited closed, resting state receptors at similar concentrations, decreasing the channel opening rate and shifting the GABA concentration-response curve to the right. R mTFD-MPPB, like most anaesthetics, enhanced receptor gating by rapidly binding to allosteric sites on open channels, initiating a rate-limiting conformation change to stabilized open channel states. These states had slower closing rates, thus shifting the GABA concentration-response curve to the left. Under conditions when most GABAA Rs were open, an inhibitory action of R-mTFD-MPPB was revealed that had a similar IC50 to that of S-mTFD-MPPB. Thus, the inhibitory sites are not enantioselective, and the convulsant action of S-mTFD-MPPB results from its negligible affinity for the enhancing, anaesthetic sites. Interactions with these two classes of barbiturate binding sites on GABAA Rs underlie the enantiomers' different pharmacological activities in mice. PMID- 26378887 TI - Evaluation of Kinase Activity Profiling Using Chemical Proteomics. AB - Protein kinases are important mediators of intracellular signaling and are reversibly activated by phosphorylation. Immobilized kinase inhibitors can be used to enrich these often low-abundance proteins, to identify targets of kinase inhibitors, or to probe their selectivity. It has been suggested that the binding of kinases to affinity beads reflects a kinase's activation status, a concept that is under considerable debate. To assess the merits of the idea, we performed a series of experiments including quantitative phosphoproteomics and purification of kinases by single or mixed affinity matrices from signaling activated or resting cancer cells. The data show that mixed affinity beads largely bind kinases independent of their activation status, and experiments using individual immobilized kinase inhibitors show mixed results in terms of preference for binding the active or inactive conformation. Taken together, activity- or conformation-dependent binding to such affinity resins depends (i) on the kinase, (ii) on the affinity probe, and (iii) on the activation status of the lysate or cell. As a result, great caution should be exercised when inferring kinase activity from such binding data. The results also suggest that assaying kinase activity using binding data is restricted to a limited number of well-chosen cases. PMID- 26378886 TI - Palladium-catalyzed enantioselective 1,1-fluoroarylation of aminoalkenes. AB - The development of an enantioselective palladium-catalyzed 1,1-fluoroarylation of unactivated aminoalkenes is described. The reaction uses arylboronic acids as the arene source and Selectfluor as the fluorine source to generate benzylic fluorides in good yields with excellent enantioselectivities. This transformation, likely proceeding through an oxidative Heck mechanism, affords 1,1-difunctionalized alkene products. PMID- 26378888 TI - Development and validation of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of tigecycline in rat brain tissues. AB - Tigecycline (TIG), a derivative of minocycline, is the first in the novel class of glycylcyclines and is currently indicated for the treatment of complicated skin structure and intra-abdominal infections. A selective, accurate and reversed phase high-performance liquid chromatography-tandem mass spectrometry (HPLC MS/MS) method was developed for the determination of TIG in rat brain tissues. Sample preparation was based on protein precipitation and solid phase extraction using Supel-Select HLB (30 mg/1 mL) cartridges. The samples were separated on a YMC Triart C18 column (150 mm x 3.0 mm. 3.0 um) using gradient elution. Positive electrospray ionization (ESI+) was used for the detection mechanism with the multiple reaction monitoring (MRM) mode. The method was validated over the concentration range of 150-1200 ng/mL for rat brain tissue. The precision and accuracy for all brain analyses were within the acceptable limit. The mean extraction recovery in rat brain was 83.6%. This validated method was successfully applied to a pharmacokinetic study in female Sprague Dawley rats, which were given a dose of 25 mg/kg TIG intraperitoneally at various time-points. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26378889 TI - Value-Based Payments Require Valuing What Matters to Patients. PMID- 26378890 TI - Significant enhancement of negative secondary ion yields by cluster ion bombardment combined with cesium flooding. AB - In secondary ion mass spectrometry (SIMS), the beneficial effect of cesium implantation or flooding on the enhancement of negative secondary ion yields has been investigated in detail for various semiconductor and metal samples. All results have been obtained for monatomic ion bombardment. Recent progress in SIMS is based to a large extent on the development and use of cluster primary ions. In this work we show that the enhancement of negative secondary ions induced by the combination of ion bombardment with simultaneous cesium flooding is valid not only for monatomic ion bombardment but also for cluster primary ions. Experiments carried out using C60+ and Ar4000+ bombardment on silicon show that yields of negative secondary silicon ions can be optimized in the same way as by Ga+ and Cs+ bombardment. Both for monatomic and cluster ion bombardment, the optimization does not depend on the primary ion species. Hence, it can be assumed that the silicon results are also valid for other cluster primary ions and that results obtained for monatomic ion bombardment on other semiconductor and metal samples are also valid for cluster ion bombardment. In SIMS, cluster primary ions are also largely used for the analysis of organic matter. For polycarbonate, our results show that Ar4000+ bombardment combined with cesium flooding enhances secondary ion signals by a factor of 6. This can be attributed to the removal of charging effects and/or reduced fragmentation, but no major influence on ionization processes can be observed. The use of cesium flooding for the imaging of cells was also investigated and a significant enhancement of secondary ion yields was observed. Hence, cesium flooding has also a vast potential for SIMS analyses with cluster ion bombardment. PMID- 26378891 TI - Origin of Fluorine/Sulfur Gauche Effect of beta-Fluorinated Thiol, Sulfoxide, Sulfone, and Thionium Ion. AB - The well-known gauche preference in FCCX systems, where X is an electronegative element from Period 2, is widely exploited in synthetic, medicinal, and material chemistry. It is rationalized on the basis of sigma(C-H) -> sigma*(C-F) hyperconjugation and electrostatic interactions. The recent report (Thiehoff, C.; et al. Chem. Sci. 2015, 6, 3565) showed that the fluorine gauche effect can extend to Period 3 elements, such as sulfur. The aim of the present work is to disclose factors governing conformational behavior of FCCS containing systems. We examine conformational preferences in seven classes of compounds by ab initio and DFT calculations and rationalize the results by quantitatively decomposing the anti/gauche isomerization energy into contributions from electrostatic, orbital, dispersion, and Pauli interactions, and energy spent on structural changes. The results show that the fluorine/sulfur gauche effect is primarily electrostatic (63-75%), while all orbital interactions contribute 22-41% to stabilizing interactions. Stereoelectronic effects, involved in orbital interactions, also play a role in gauche conformer stabilization. PMID- 26378892 TI - Ethnic Variation in Response to IM Triamcinolone in Children With Severe Therapy Resistant Asthma. AB - BACKGROUND: Although ethnicity may influence response to treatment of patients with asthma, this approach is controversial. The objective of this study was to determine if ethnicity influences the response to IM steroid use (eliminating adherence as an issue). METHODS: Children with severe therapy-resistant asthma who had previously undergone a detailed assessment (including a nurse-led hospital and home visit in which potentially modifiable factors had been identified and addressed) were admitted for further evaluation; this evaluation included assessment of steroid response. Children were classified as white, black, Asian, or mixed white/black. Steroid responsiveness was defined according to symptoms (Asthma Control Test), inflammation (sputum eosinophil count and exhaled nitric oxide), and spirometry (FEV1); these variables were measured before and 4 weeks after IM triamcinolone use. Data were collected regarding exacerbations. Fractional exhaled nitric oxide (Feno) response was defined as a decrease to < 24 parts per billion (ppb). RESULTS: Seventy-nine subjects were identified (white, n = 54 [68%]; black, n = 16 [20%]; Asian, n = 5 [6%]; and mixed white/black, n = 4 [5%]). After administration of triamcinolone, there was a significant drop in median Feno in white children (46.8 to 23.1 ppb; P < .001) but not in black children (52.2 to 34.5 ppb; P = .58). More black children than white children (86.7%) were Feno nonresponders (86.7% vs 45.3%; P < .05), and more black children had exacerbations compared with white children (61% vs 17%; P < .05). CONCLUSIONS: Black children with asthma were less likely to report an Feno response and had more exacerbations 4 weeks after administration of triamcinolone than white children. Further research is needed to understand the mechanisms of these differences, but they cannot be due to differences in adherence or access to care. PMID- 26378894 TI - Effects of the boscalid fungicide Filan(r) on the marine amphipod Allorchestes compressa at environmentally relevant concentrations. AB - Fungicides are widely used in agriculture to control fungal diseases. After application, fungicides can be transported offsite to surface and groundwater and ultimately enter estuarine and marine environments. The presence of fungicides in the marine environment may pose risks to marine organisms, but little is known about fungicide effects on these organisms, especially invertebrates. The present study investigated the effects of the commonly used boscalid fungicide Filan(r) on life history traits, feeding rate, and energy reserves (lipid, glycogen, and protein content) of the marine amphipod Allorchestes compressa over 6 wk under laboratory conditions. Amphipods were exposed to 3 concentrations of Filan (1 MUg, 10 MUg, and 40 MUg active ingredient [a.i.]/L), with 5 replicates per treatment. Lipid content and reproduction were the most sensitive measures of effect, with lipid content reduced by 53.8% at the highest concentration. Survival, growth, and other energy reserves of amphipods were also negatively affected by Filan, and the effects were concentration dependent. Antennal deformities were incidentally observed on the amphipods at a concentration of 40 MUg a.i./L. The results of the present study indicate comprehensive effects of the boscalid fungicide Filan on A. compressa at environmentally relevant concentrations. The decline or absence of A. compressa in marine ecosystems could impair the ecosystem function because of their important role in trophic transfer and nutrient recycling. The authors' results suggest that even though the use of fungicides is often regarded as posing only a minor risk to aquatic organisms, the assessment of their long-term effects is critical. PMID- 26378893 TI - Targeting Inhibitor of Apoptosis Proteins Protects from Bleomycin-Induced Lung Fibrosis. AB - Accumulation of apoptosis-resistant fibroblasts is a hallmark of pulmonary fibrosis. We hypothesized that disruption of inhibitor of apoptosis protein (IAP) family proteins would limit lung fibrosis. We first show that transforming growth factor-beta1 and bleomycin increase X-linked IAP (XIAP) and cellular IAP (cIAP)-1 and -2 in murine lungs and mesenchymal cells. Functional blockade of XIAP and the cIAPs with AT-406, an orally bioavailable second mitochondria-derived activator of caspases (Smac) mimetic, abrogated bleomycin-induced lung fibrosis when given both prophylactically and therapeutically. To determine whether the reduction in fibrosis was predominantly due to AT-406-mediated inhibition of XIAP, we compared the fibrotic response of XIAP-deficient mice (XIAP(-/y)) with littermate controls and found no difference. We found no alterations in total inflammatory cells of either wild-type mice treated with AT-406 or XIAP(-/y) mice. AT-406 treatment limited CCL12 and IFN-gamma production, whereas XIAP(-/y) mice exhibited increased IL-1beta expression. Surprisingly, XIAP(-/y) mesenchymal cells had increased resistance to Fas-mediated apoptosis. Functional blockade of cIAPs with AT-406 restored sensitivity to Fas-mediated apoptosis in XIAP(-/y) mesenchymal cells in vitro and increased apoptosis of mesenchymal cells in vivo, indicating that the increased apoptosis resistance in XIAP(-/y) mesenchymal cells was the result of increased cIAP expression. Collectively, these results indicate that: (1) IAPs have a role in the pathogenesis of lung fibrosis; (2) a congenital deficiency of XIAP may be overcome by compensatory mechanisms of other IAPs; and (3) broad functional inhibition of IAPs may be an effective strategy for the treatment of lung fibrosis by promoting mesenchymal cell apoptosis. PMID- 26378895 TI - Association of Behavioral Risk Factors for Chronic Diseases With Physical and Mental Health in European Adults Aged 50 Years or Older, 2004-2005. AB - INTRODUCTION: Noncommunicable diseases are the leading cause of illness and death worldwide; behavioral risk factors (BRFs) contribute to these diseases. We assessed the presence of multiple BRFs among European adults according to their physical and mental health status. METHODS: We used data from 26,026 adults aged 50 years or older from 11 countries that participated in the Survey of Health, Ageing and Retirement in Europe (2004-2005). BRFs (overweight or obesity, smoking, physical inactivity, and risky alcohol consumption) were assessed according to physical health (ie, presence of chronic diseases, disease symptoms, or limitations in activities of daily living) and mental health (depression) through multiple regression estimations. RESULTS: Overweight or obesity in men and physical inactivity in women were the most prevalent BRFs. Compared with physically active adults, physically inactive adults had a higher mean number of chronic diseases (1.33 vs 1.26) and chronic disease symptoms (1.55 vs 1.47). Risky alcohol consumption (>=4 servings of an alcohol beverage >=3 times a week) was associated with a higher mean depression score (2.84 vs 2.47). Compared with adults with 0 or 1 BRF, adults with 2 or more BRFs had significantly higher odds of having 1 or more chronic diseases (men: 1.52; women: 1.73) and functional limitations (men: 1.65; women: 1.79) and higher prevalence of high blood pressure (37.8% vs 28.2). Belgian adults with BRFs had the highest mean number of chronic diseases or functional limitations among those who were overweight or obese and the highest mean number of chronic diseases and disease symptoms among those who smoked and were physically inactive. CONCLUSION: We found revealed significant positive associations between BRFs and poor health among middle-aged and older European adults. Primary health care intervention programs should focus on developing ways to reduce BRF prevalence in this population. PMID- 26378896 TI - Disparities in Patterns of Health Care Travel Among Inpatients Diagnosed With Congestive Heart Failure, Florida, 2011. AB - INTRODUCTION: Congestive heart failure (CHF) is a major public health problem in the United States and is a leading cause of hospitalization in the elderly population. Understanding the health care travel patterns of CHF patients and their underlying cause is important to balance the supply and demand for local hospital resources. This article explores the nonclinical factors that prompt CHF patients to seek distant instead of local hospitalization. METHODS: Local hospitalization was defined as inpatients staying within hospital service areas, and distant hospitalization was defined as inpatients traveling outside hospital service areas, based on individual hospital discharge data in 2011 generated by a Dartmouth-Swiss hybrid approach. Multiple logistic and linear regression models were used to compare the travel patterns of different groups of inpatients in Florida. RESULTS: Black patients, no-charge patients, patients living in large metropolitan areas, and patients with a low socioeconomic status were more likely to seek local hospitalization than were white patients, those who were privately insured, those who lived in rural areas, and those with a high socioeconomic status, respectively. CONCLUSION: Findings indicate that different populations diagnosed with CHF had different travel patterns for hospitalization. Changes or disruptions in local hospital supply could differentially affect different groups in a population. Policy makers could target efforts to CHF patients who are less likely to travel to seek treatment. PMID- 26378897 TI - The Process of Cessation Among Current Tobacco Smokers: A Cross-Sectional Data Analysis From 21 Countries, Global Adult Tobacco Survey, 2009-2013. AB - We analyzed data from the Global Adult Tobacco Survey (GATS) from 21 countries to categorize smokers by stages of cessation and highlight interventions that could be tailored to each stage. GATS is a nationally representative household survey that measures tobacco use and other key indicators by using a standardized protocol. The distribution of smokers into precontemplation, contemplation, and preparation stages varied by country. Using the stages of change model, each country can design and implement effective interventions suitable to its cultural, social, and economic situations to help smokers advance successfully through the stages of cessation. PMID- 26378898 TI - Disparities in Potentially Preventable Hospitalizations for Chronic Conditions Among Korean Americans, Hawaii, 2010-2012. AB - INTRODUCTION: Korean Americans are a growing but understudied population group in the United States. High rates of potentially preventable hospitalizations suggest that primary care is underutilized. We compared preventable hospitalizations for chronic conditions in aggregate and for congestive heart failure (CHF) for Korean Americans and whites in Hawaii. METHODS: Discharge data from 2010 to 2012 for all hospitalizations of adults in Hawaii for preventable hospitalizations in aggregate and for CHF included 4,345 among Korean Americans and 81,570 among whites. Preventable hospitalization rates for chronic conditions and CHF were calculated for Korean Americans and whites by sex and age group (18-64 y vs >=65 y). Unadjusted rate ratios for Korean Americans were calculated relative to whites. Multivariate models, controlling for insurance type and comorbidity, provided adjusted rate ratios (aRRs). RESULTS: Korean American women and men aged 65 or older were at greater risk of preventable hospitalization overall than white women (aRR, 2.48; P = .003) and white men (aRR, 1.82; P = .049). Korean American men aged 65 or older also were at greater risk of hospitalization for CHF relative to white men (aRR, 1.87; P = .04) and for older Korean American women (aRR, 1.75; P = .07). Younger age groups did not differ significantly. CONCLUSION: Older Korean American patients may have significant disparities in preventable hospitalizations, which suggests poor access to or poor quality of primary health care. Improving primary care for Korean Americans may prevent unnecessary hospitalizations, improve quality of life for Korean Americans with chronic illness, and reduce health care costs. PMID- 26378899 TI - The Availability of Competitive Foods and Beverages to Middle School Students in Appalachian Virginia Before Implementation of the 2014 Smart Snacks in School Standards. AB - The study objective was to examine the nutritional quality of competitive foods and beverages (foods and beverages from vending machines and a la carte foods) available to rural middle school students, before implementation of the US Department of Agriculture's Smart Snacks in School standards in July 2014. In spring 2014, we audited vending machines and a la carte cafeteria foods and beverages in 8 rural Appalachian middle schools in Virginia. Few schools had vending machines. Few a la carte and vending machine foods met Smart Snacks in School standards (36.5%); however, most beverages did (78.2%). The major challenges to meeting standards were fat and sodium content of foods. Most competitive foods (62.2%) did not meet new standards, and rural schools with limited resources will likely require assistance to fully comply. PMID- 26378900 TI - Strategies to Improve the Integration of Community Health Workers Into Health Care Teams: "A Little Fish in a Big Pond". AB - INTRODUCTION: The Patient Protection and Affordable Care Act acknowledges the value of community health workers (CHWs) as frontline public health workers. Consequently, growing attention has been placed on promoting CHWs as legitimate partners to provide support to health care teams and patients in the prevention, management, and control of chronic disease, particularly among diverse populations and high-need individuals. METHODS: Using a mixed-methods research approach, we investigated the integration of CHWs into health care teams from the CHW perspective. We conducted a survey of 265 CHWs and interviews with 23 CHWs to better understand and describe their experience and their perceived opportunities and challenges regarding their integration within the context of health care reform. RESULTS: Feelings of organizational support were positively correlated with the number of CHWs in the organization. CHWs reported the following facilitators to integration: having team meetings (73.7%), training inside (70.4%) and outside of the organization (81.6%), access to electronic health records, and ability for CHWs to stay connected to the community. CONCLUSION: The perspectives of CHWs on their positive and negative experiences offer useful and innovative insight into ways of maximizing their impact on the health care team, patients, and their role as key emissaries between clinical services and community resources. PMID- 26378901 TI - 3D Reconstruction of Quasi-1D Single-Crystal Nanostructures. AB - The accurate determination of the 3D geometries of single-crystal quasi-1D nanostructures is described, including sidelengths, perimeters, areas, lengths, and azimuth and elevation angles. This is a major step toward the synthesis of quasi-1D nanostructures with superior uniformity, and tightly controlled geometrical or geometry-dependent properties. PMID- 26378902 TI - Smooth muscle tissue engineering in crosslinked electrospun gelatin scaffolds. AB - Crosslinked, multi-layer electrospun gelatin fiber scaffolds with generally +/-45 degree fiber orientation have been used to grow human umbilical vein smooth muscle cells (HUVSMCs) to create a vascular tunica media graft. Scaffolds of different fiber diameter (2-5 MUm in wet state), pore size, and porosity (16-21% in wet state) were assessed in terms of cell adherence and viability, cell proliferation, and migration in both in-plane and transverse directions through the scaffold as a function of time under static cell culture conditions. HUVSMC cell viability reached between 80 and 92% for all scaffolds after 9 days in culture. HUVSMCs adhered, elongated, and orientated in the fiber direction, and migrated through a scaffold thickness of 200-235 MUm 9 days post-seeding under static conditions. The best scaffold was then used to assess the tissue engineering of HUVSMCs under dynamic conditions for a rotating, cell seeded, tubular scaffold in the bioreactor containing the culture medium. Dynamic conditions almost doubled the rate of cell proliferation through the scaffold, forming full tissue throughout a scaffold of 250-300 MUm thickness 6 days post seeding. PMID- 26378903 TI - Erratum. PMID- 26378904 TI - Primary Tumor Resection in Metastatic Colorectal Cancer: Please Pass the Salt. PMID- 26378905 TI - Arthroscopic Partial Meniscectomy for Meniscal Tears: A Review and Commentary on a Study by NEJM. AB - Arthroscopic partial meniscectomy (APM) has been demonstrated to be effective when performed in the appropriately indicated patient. However, a recent study published in the New England Journal of Medicine (NEJM) questioned whether or not the procedure actually had any clinical benefit whatsoever. Despite being a prospective, Level 1, randomized study, there are several aspects of the study that must be taken into consideration when interpreting the findings, including but not limited to the patient selection criteria, limited sample size, and lack of information regarding meniscal tear patterns. This study will critically review the recently published NEJM article, as well as analyze and assess the current body of APM literature. PMID- 26378906 TI - Patient-Specific Instrumentation in Total Knee Arthroplasty: What Is the Evidence? AB - With a steady increase in the demand for primary and revision total knee arthroplasty (TKA), any potential reduction in the number of failures can be a topic of significant clinical importance. Patient-specific instrumentation (PSI) is introduced to potentially achieve more reproducible alignment with reduced outliers by creating more accurate and patient-specific femoral and tibial cuts based on neutral mechanical axis. However, there is no widely accepted consensus on the efficacy and indication of using PSI in TKA. The purpose of this review was to assess the current literature on patient-specific TKA and its effect on perioperative outcomes, including templating and preoperative planning, mechanical alignment, clinical outcomes, perioperative blood loss, and economic evaluations. Based on the current literature, more prospective studies are necessary to evaluate the routine use of PSI in TKA. PMID- 26378907 TI - Role of Osteotomy in Posterolateral Instability of the Knee. AB - Injuries to the posterolateral corner (PLC) can be difficult injuries to successfully treat and are often associated with other injuries around the knee. Patients with varus malalignment can be even more difficult to manage when they have a PLC injury, resulting in double or triple varus and subsequent varus thrust during gait. A high tibial osteotomy (HTO) is a useful and necessary operation in patients with varus malalignment and a PLC injury, particularly in the chronic setting. The biomechanics, indications, surgical approach, and outcomes of HTO in the setting of PLC injury are reviewed in this article. PMID- 26378909 TI - Integrated Source Case Investigation for Tuberculosis (TB) and HIV in the Caregivers and Household Contacts of Hospitalised Young Children Diagnosed with TB in South Africa: An Observational Study. AB - BACKGROUND: Contact tracing, to identify source cases with untreated tuberculosis (TB), is rarely performed in high disease burden settings when the index case is a young child with TB. As TB is strongly associated with HIV infection in these settings, we used source case investigation to determine the prevalence of undiagnosed TB and HIV in the caregivers and household contacts of hospitalised young children diagnosed with TB in South Africa. METHODS: Caregivers and household contacts of 576 young children (age <=7 years) with TB diagnosed between May 2010 and August 2012 were screened for TB and HIV. The primary outcome was the detection of laboratory-confirmed, newly-diagnosed TB disease and/or HIV-infection in close contacts. RESULTS: Of 576 caregivers, 301 (52.3%) self-reported HIV-positivity. Newly-diagnosed HIV infection was detected in 63 (22.9%) of the remaining 275 caregivers who self-reported an unknown or negative HIV status. Screening identified 133 (23.1%) caregivers eligible for immediate anti-retroviral therapy (ART). Newly-diagnosed TB disease was detected in 23 (4.0%) caregivers. In non-caregiver household contacts (n = 1341), the prevalence of newly-diagnosed HIV infection and TB disease was 10.0% and 3.2% respectively. On average, screening contacts of every nine children with TB resulted in the identification of one case of newly-diagnosed TB disease, three cases of newly diagnosed HIV-infection, and three HIV-infected persons eligible for ART. CONCLUSION: In high burden countries, source case investigation yields high rates of previously undiagnosed HIV and TB infection in the close contacts of hospitalised young children diagnosed with TB. Furthermore, integrated screening identifies many individuals who are eligible for immediate ART. Similar studies, with costing analyses, should be undertaken in other high burden settings integrated source case investigation for TB and HIV should be routinely undertaken if our findings are confirmed. PMID- 26378908 TI - Tubal ligation and ovarian cancer risk in a large cohort: Substantial variation by histological type. AB - Histopathological and molecular studies suggest that different histological subtypes (histotypes) of ovarian cancer have different aetiologies. Few studies have been large enough to explore reliably the effect of tubal ligation (sterilization), which has been associated with a reduced overall risk of ovarian cancer, on different tumour histotypes. In a prospective study of 1.1 million UK women without prior cancer or bilateral oophorectomy, 8,035 ovarian cancers occurred during mean follow-up of 13.8 years. Using a Cox proportional hazards model, we estimated adjusted relative risks of ovarian cancer associated with tubal ligation. Overall, there was substantial heterogeneity in tumour risk associated with tubal ligation for the four main histotypes, serous, endometrioid, mucinous and clear cell (heterogeneity: p < 0.0001). For serous tumours, the most common histotype (n = 3,515), risks differed significantly between high-grade (RR: 0.77, 95% CI: 0.67-0.89) and low-grade tumours (RR: 1.13, 95% CI: 0.89-1.42); heterogeneity: p = 0.007. Relative risks were almost halved for endometrioid (n = 690, RR: 0.54, 95% CI: 0.43-0.69) and clear cell tumours (n = 401, RR: 0.55, 95% CI: 0.39-0.77), but there was no association between tubal ligation and mucinous tumours (n = 836, RR: 0.99, 95% CI: 0.84-1.18). For the main tumour histotypes we found little variation of risk by timing of tubal ligation. The significant differences by tumour histotype are unlikely to be due to confounding and are consistent with hypotheses that high-grade and low-grade serous tumours have different origins, and that some endometrioid and clear cell tumours might arise from cells and/or carcinogens travelling through the fallopian tubes. PMID- 26378910 TI - Local and Regional Impacts of Pollution on Coral Reefs along the Thousand Islands North of the Megacity Jakarta, Indonesia. AB - Worldwide, coral reefs are challenged by multiple stressors due to growing urbanization, industrialization and coastal development. Coral reefs along the Thousand Islands off Jakarta, one of the largest megacities worldwide, have degraded dramatically over recent decades. The shift and decline in coral cover and composition has been extensively studied with a focus on large-scale gradients (i.e. regional drivers), however special focus on local drivers in shaping spatial community composition is still lacking. Here, the spatial impact of anthropogenic stressors on local and regional scales on coral reefs north of Jakarta was investigated. Results indicate that the direct impact of Jakarta is mainly restricted to inshore reefs, separating reefs in Jakarta Bay from reefs along the Thousand Islands further north. A spatial patchwork of differentially degraded reefs is present along the islands as a result of localized anthropogenic effects rather than regional gradients. Pollution is the main anthropogenic stressor, with over 80% of variation in benthic community composition driven by sedimentation rate, NO2, PO4 and Chlorophyll a. Thus, the spatial structure of reefs is directly related to intense anthropogenic pressure from local as well as regional sources. Therefore, improved spatial management that accounts for both local and regional stressors is needed for effective marine conservation. PMID- 26378912 TI - Chlamydia trachomatis IgG3 seropositivity is associated with gastroschisis. AB - OBJECTIVE: To investigate the association between Chlamydia trachomatis (CT) infection seropositivity and gastroschisis. STUDY DESIGN: In this case-control study we enrolled pregnant women either prenatally diagnosed with gastroschisis (cases, n=33) or with a normal ultrasound (controls, n=66). Both groups attended the University of Utah's Maternal Fetal Medicine Diagnostic Center for their diagnostic ultrasound or because of a community obstetrician referral. Participants completed a structured interview on potential risk factors. Anti-CT immunoglobulin (IgG)1 and IgG3 were measured by a CT elementary body enzyme linked immunosorbent assay. RESULT: Median age at sexual debut was lower and reported sexual partner number higher in cases compared with controls. Risk factors for gastroschisis included having ? 3 sexual partners (odds ratio (OR)=3.3, 95% CI 1.2, 9.4), change in partner from the previous pregnancy (OR=3.6, 95% CI 0.9, 13.9) and anti-CT IgG3 seropositivity (age-adjusted OR=3.9, 95% CI: 1.1, 13.2). CONCLUSION: Anti-CT IgG3 seropositivity was associated with greater than a threefold risk for gastroschisis. PMID- 26378911 TI - Identifying Breeding Priorities for Blueberry Flavor Using Biochemical, Sensory, and Genotype by Environment Analyses. AB - Breeding for a subjective goal such as flavor is challenging, as many blueberry cultivars are grown worldwide, and identifying breeding targets relating to blueberry flavor biochemistry that have a high degree of genetic control and low environmental variability are priorities. A variety of biochemical compounds and physical characters induce the sensory responses of taste, olfaction, and somatosensation, all of which interact to create what is perceived flavor. The goal of this study was to identify the flavor compounds with a larger genetic versus environmental component regulating their expression over an array of cultivars, locations, and years. Over the course of three years, consumer panelists rated overall liking, texture, sweetness, sourness, and flavor intensity of 19 southern highbush blueberry (Vaccinium corymbosum hybrids) genotypes in 30 sensory panels. Significant positive correlations to overall liking of blueberry fruit (P<0.001) were found with sweetness (R2 = 0.70), texture (R2 = 0.68), and flavor (R2 = 0.63). Sourness had a significantly negative relationship with overall liking (R2 = 0.55). The relationship between flavor and texture liking was also linear (R2 = 0.73, P<0.0001) demonstrating interaction between olfaction and somatosensation. Partial least squares analysis was used to identify sugars, acids, and volatile compounds contributing to liking and sensory intensities, and revealed strong effects of fructose, pH, and several volatile compounds upon all sensory parameters measured. To assess the feasibility of breeding for flavor components, a three year study was conducted to compare genetic and environmental influences on flavor biochemistry. Panelists could discern genotypic variation in blueberry sensory components, and many of the compounds affecting consumer favor of blueberries, such as fructose, pH, beta caryophyllene oxide and 2-heptanone, were sufficiently genetically controlled that allocating resources for their breeding is worthwhile. PMID- 26378913 TI - Early neonatal deaths with perinatal asphyxia in very low birth weight Brazilian infants. AB - OBJECTIVE: The objective of this study was to assess the frequency of early deaths associated with birth asphyxia of very low birth weight infants between 2005 and 2010, in Brazil. STUDY DESIGN: This population study enrolled all live births with birth weight from 400 to 1499 g, gestational age ? 22 weeks, without malformations that died up to 6 days after birth with perinatal asphyxia. Asphyxia was defined if intrauterine hypoxia, asphyxia at birth or meconium aspiration syndrome were written in any line of the death certificate. Active search was carried out in 27 Brazilian federative units. RESULT: For every 1000 live births of very low birth weight infants without congenital malformations, 40.25 and 32.38 died with birth asphyxia in the first week after birth, respectively, in 2005 and 2010 (P<0.001). The contribution of birth asphyxia to early neonatal death of these infants was approximately 10 to 12% all study years. CONCLUSION: Reduction of birth asphyxia in very low birth weight infants is essential to reducing neonatal mortality in Brazil. PMID- 26378914 TI - Obesity and Aerobic Fitness among Urban Public School Students in Elementary, Middle, and High School. AB - AIMS AND OBJECTIVES: To assess the prevalence of cardiovascular disease risk among urban public school students through a collaborative school district and university partnership. METHODS: Children and adolescents in grades K-12 from 24 urban public schools participated in measurements of height, weight, and other health metrics during the 2009-2010 school year. Body mass index (BMI) percentiles and z-scores were computed for 4673 students. President's Challenge 1 mile endurance run was completed by 1075 students ages 9-19 years. Maximal oxygen consumption (?O2max) was predicted using an age-, sex-, and BMI-specific formula to determine health-related fitness. Resting blood pressure (BP) was assessed in 1467 students. Regression analyses were used to compare BMI z-scores, fitness, and age- and sex-specific BP percentiles across grade levels. Chi-square tests were used to explore the effect of sex and grade-level on health-related outcomes. RESULTS: Based on BMI, 19.8% were categorized as overweight and 24.4% were obese. Included in the obese category were 454 students (9.7% of sample) classified with severe obesity. Using FITNESSGRAM criteria, 50.2% of students did not achieve the Healthy Fitness Zone (HFZ); the proportion of students in the Needs Improvement categories increased from elementary to middle school to high school. Male students demonstrated higher fitness than female students, with 61.4% of boys and only 35.4% of girls meeting HFZ standards. Elevated BP was observed among 24% of 1467 students assessed. Systolic and diastolic BP z-scores revealed low correlation with BMI z-scores. CONCLUSIONS: A community-university collaboration identified obesity, severe obesity, overweight, and low aerobic fitness to be common risk factors among urban public school students. PMID- 26378915 TI - Lithium Decreases Glial Fibrillary Acidic Protein in a Mouse Model of Alexander Disease. AB - Alexander disease is a fatal neurodegenerative disease caused by mutations in the astrocyte intermediate filament glial fibrillary acidic protein (GFAP). The disease is characterized by elevated levels of GFAP and the formation of protein aggregates, known as Rosenthal fibers, within astrocytes. Lithium has previously been shown to decrease protein aggregates by increasing the autophagy pathway for protein degradation. In addition, lithium has also been reported to decrease activation of the transcription factor STAT3, which is a regulator of GFAP transcription and astrogliogenesis. Here we tested whether lithium treatment would decrease levels of GFAP in a mouse model of Alexander disease. Mice with the Gfap-R236H point mutation were fed lithium food pellets for 4 to 8 weeks. Four weeks of treatment with LiCl at 0.5% in food pellets decreased GFAP protein and transcripts in several brain regions, although with mild side effects and some mortality. Extending the duration of treatment to 8 weeks resulted in higher mortality, and again with a decrease in GFAP in the surviving animals. Indicators of autophagy, such as LC3, were not increased, suggesting that lithium may decrease levels of GFAP through other pathways. Lithium reduced the levels of phosphorylated STAT3, suggesting this as one pathway mediating the effects on GFAP. In conclusion, lithium has the potential to decrease GFAP levels in Alexander disease, but with a narrow therapeutic window separating efficacy and toxicity. PMID- 26378917 TI - Changes in Laminin Expression Pattern during Early Differentiation of Human Embryonic Stem Cells. AB - Laminin isoforms laminin-511 and -521 are expressed by human embryonic stem cells (hESC) and can be used as a growth matrix to culture these cells under pluripotent conditions. However, the expression of these laminins during the induction of hESC differentiation has not been studied in detail. Furthermore, the data regarding the expression pattern of laminin chains in differentiating hESC is scarce. In the current study we aimed to fill this gap and investigated the potential changes in laminin expression during early hESC differentiation induced by retinoic acid (RA). We found that laminin-511 but not -521 accumulates in the committed cells during early steps of hESC differentiation. We also performed a comprehensive analysis of the laminin chain repertoire and found that pluripotent hESC express a more diverse range of laminin chains than shown previously. In particular, we provide the evidence that in addition to alpha1, alpha5, beta1, beta2 and gamma1 chains, hESC express alpha2, alpha3, beta3, gamma2 and gamma3 chain proteins and mRNA. Additionally, we found that a variant of laminin alpha3 chain-145 kDa-accumulated in RA-treated hESC showing that these cells produce prevalently specifically modified version of alpha3 chain in early phase of differentiation. PMID- 26378916 TI - ARID1A Is Essential for Endometrial Function during Early Pregnancy. AB - AT-rich interactive domain 1A gene (ARID1A) loss is a frequent event in endometriosis-associated ovarian carcinomas. Endometriosis is a disease in which tissue that normally grows inside the uterus grows outside the uterus, and 50% of women with endometriosis are infertile. ARID1A protein levels were significantly lower in the eutopic endometrium of women with endometriosis compared to women without endometriosis. However, an understanding of the physiological effects of ARID1A loss remains quite poor, and the function of Arid1a in the female reproductive tract has remained elusive. In order to understand the role of Arid1a in the uterus, we have generated mice with conditional ablation of Arid1a in the PGR positive cells (Pgrcre/+Arid1af/f; Arid1ad/d). Ovarian function and uterine development of Arid1ad/d mice were normal. However, Arid1ad/d mice were sterile due to defective embryo implantation and decidualization. The epithelial proliferation was significantly increased in Arid1ad/d mice compared to control mice. Enhanced epithelial estrogen activity and reduced epithelial PGR expression, which impedes maturation of the receptive uterus, was observed in Arid1ad/d mice at the peri-implantation period. The microarray analysis revealed that ARID1A represses the genes related to cell cycle and DNA replication. We showed that ARID1A positively regulates Klf15 expression with PGR to inhibit epithelial proliferation at peri-implantation. Our results suggest that Arid1a has a critical role in modulating epithelial proliferation which is a critical requisite for fertility. This finding provides a new signaling pathway for steroid hormone regulation in female reproductive biology and furthers our understanding of the molecular mechanisms that underlie dysregulation of hormonal signaling in human reproductive disorders such as endometriosis. PMID- 26378918 TI - Hypoglycin A Content in Blood and Urine Discriminates Horses with Atypical Myopathy from Clinically Normal Horses Grazing on the Same Pasture. AB - Hypoglycin A (HGA) in seeds of Acer spp. is suspected to cause seasonal pasture myopathy in North America and equine atypical myopathy (AM) in Europe, fatal diseases in horses on pasture. In previous studies, this suspicion was substantiated by the correlation of seed HGA content with the concentrations of toxic metabolites in urine and serum (MCPA-conjugates) of affected horses. However, seed sampling was conducted after rather than during an outbreak of the disease. The aim of this study was to further confirm the causality between HGA occurrence and disease outbreak by seed sampling during an outbreak and the determination of i) HGA in seeds and of ii) HGA and MCPA-conjugates in urine and serum of diseased horses. Furthermore, cograzing healthy horses, which were present on AM affected pastures, were also investigated. AM-pastures in Germany were visited to identify seeds of Acer pseudoplatanus and serum (n = 8) as well as urine (n = 6) from a total of 16 diseased horses were analyzed for amino acid composition by LC-ESI-MS/MS, with a special focus on the content of HGA. Additionally, the content of its toxic metabolite was measured in its conjugated form in body fluids (UPLC-MS/MS). The seeds contained 1.7-319.8 MUg HGA/g seed. The content of HGA in serum of affected horses ranged from 387.8-8493.8 MUg/L (controls < 10 MUg/L), and in urine from 143.8-926.4 MUg/L (controls < 10 MUg/L), respectively. Healthy cograzing horses on AM-pastures showed higher serum (108.8 +/- 83.76 MUg/L) and urine concentrations (26.9 +/- 7.39 MUg/L) compared to control horses, but lower concentrations compared to diseased horses. The range of MCPA-carnitine and creatinine concentrations found in diseased horses in serum and urine were 0.17-0.65 mmol/L (controls < 0.01), and 0.34-2.05 MUmol/mmoL (controls < 0.001), respectively. MCPA-glycine levels in urine of cograzing horses were higher compared to controls. Thus, the causal link between HGA intoxication and disease outbreak could be further substantiated, and the early detection of HGA in cograzing horses, which are clinically normal, might be a promising step in prophylaxis. PMID- 26378922 TI - ESGCT and FSGT Collaborative Congress Helsinki, Finland September 17-20, 2015 Abstracts. PMID- 26378920 TI - Semaphorin7A Promotion of Tumoral Growth and Metastasis in Human Oral Cancer by Regulation of G1 Cell Cycle and Matrix Metalloproteases: Possible Contribution to Tumoral Angiogenesis. AB - BACKGROUND: Semaphorins (SEMAs) consist of a large family of secreted and membrane-anchored proteins that are important in neuronal pathfinding and axon guidance in selected areas of the developing nervous system. Of them, SEMA7A has been reported to have a chemotactic activity in neurogenesis and to be an immunomodulator; however, little is known about the relevance of SEMA7A in the behaviors of oral squamous cell carcinoma (OSCC). METHODS: We evaluated SEMA7A expression in OSCC-derived cell lines and primary OSCC samples using quantitative reverse transcriptase-polymerase chain reaction, immunoblotting, and semiquantitative immunohistochemistry (sq-IHC). In addition, SEMA7A knockdown cells (shSEMA7A cells) were used for functional experiments, including cellular proliferation, invasiveness, and migration assays. We also analyzed the clinical correlation between SEMA7A status and clinical behaviors in patients with OSCC. RESULTS: SEMA7A mRNA and protein were up-regulated significantly (P<0.05) in OSCC derived cell lines compared with human normal oral keratinocytes. The shSEMA7A cells showed decreased cellular growth by cell-cycle arrest at the G1 phase, resulting from up-regulation of cyclin-dependent kinase inhibitors (p21Cip1 and p27Kip1) and down-regulation of cyclins (cyclin D1, cyclin E) and cyclin dependent kinases (CDK2, CDK4, and CDK6); and decreased invasiveness and migration activities by reduced secretion of matrix metalloproteases (MMPs) (MMP 2, proMMP-2, pro-MMP-9), and expression of membrane type 1- MMP (MT1-MMP). We also found inactivation of the extracellular regulated kinase 1/2 and AKT pathways, an upstream molecule of cell-cycle arrest at the G1 phase, and reduced secretion of MMPs in shSEMA7A cells. sq-IHC showed that SEMA7A expression in the primary OSCCs was significantly (P = 0.001) greater than that in normal counterparts and was correlated with primary tumoral size (P = 0.0254) and regional lymph node metastasis (P = 0.0002). CONCLUSION: Our data provide evidence for an essential role of SEMA7A in tumoral growth and metastasis in OSCC and indicated that SEMA7A may play a potential diagnostic/therapeutic target for use in patients with OSCC. PMID- 26378921 TI - Bioinformatics in Africa: The Rise of Ghana? AB - Until recently, bioinformatics, an important discipline in the biological sciences, was largely limited to countries with advanced scientific resources. Nonetheless, several developing countries have lately been making progress in bioinformatics training and applications. In Africa, leading countries in the discipline include South Africa, Nigeria, and Kenya. However, one country that is less known when it comes to bioinformatics is Ghana. Here, I provide a first description of the development of bioinformatics activities in Ghana and how these activities contribute to the overall development of the discipline in Africa. Over the past decade, scientists in Ghana have been involved in publications incorporating bioinformatics analyses, aimed at addressing research questions in biomedical science and agriculture. Scarce research funding and inadequate training opportunities are some of the challenges that need to be addressed for Ghanaian scientists to continue developing their expertise in bioinformatics. PMID- 26378919 TI - Sex-dependent effects of developmental exposure to bisphenol A and ethinyl estradiol on metabolic parameters and voluntary physical activity. AB - Endocrine disrupting chemicals (EDC) have received considerable attention as potential obesogens. Past studies examining obesogenic potential of one widespread EDC, bisphenol A (BPA), have generally focused on metabolic and adipose tissue effects. However, physical inactivity has been proposed to be a leading cause of obesity. A paucity of studies has considered whether EDC, including BPA, affects this behavior. To test whether early exposure to BPA and ethinyl estradiol (EE, estrogen present in birth control pills) results in metabolic and such behavioral disruptions, California mice developmentally exposed to BPA and EE were tested as adults for energy expenditure (indirect calorimetry), body composition (echoMRI) and physical activity (measured by beam breaks and voluntary wheel running). Serum glucose and metabolic hormones were measured. No differences in body weight or food consumption were detected. BPA exposed females exhibited greater variation in weight than females in control and EE groups. During the dark and light cycles, BPA females exhibited a higher average respiratory quotient than control females, indicative of metabolizing carbohydrates rather than fats. Various assessments of voluntary physical activity in the home cage confirmed that during the dark cycle, BPA and EE exposed females were significantly less active in this setting than control females. Similar effects were not observed in BPA or EE-exposed males. No significant differences were detected in serum glucose, insulin, adiponectin and leptin concentrations. Results suggest that females developmentally exposed to BPA exhibit decreased motivation to engage in voluntary physical activity and altered metabolism of carbohydrates v. fats, which could have important health implications. PMID- 26378923 TI - Effect of MDMA-Induced Axotomy on the Dorsal Raphe Forebrain Tract in Rats: An In Vivo Manganese-Enhanced Magnetic Resonance Imaging Study. AB - 3,4-Methylenedioxymethamphetamine (MDMA), also known as "Ecstasy", is a common recreational drug of abuse. Several previous studies have attributed the central serotonergic neurotoxicity of MDMA to distal axotomy, since only fine serotonergic axons ascending from the raphe nucleus are lost without apparent damage to their cell bodies. However, this axotomy has never been visualized directly in vivo. The present study examined the axonal integrity of the efferent projections from the midbrain raphe nucleus after MDMA exposure using in vivo manganese-enhanced magnetic resonance imaging (MEMRI). Rats were injected subcutaneously six times with MDMA (5 mg/kg) or saline once daily. Eight days after the last injection, manganese ions (Mn2+) were injected stereotactically into the raphe nucleus, and a series of MEMRI images was acquired over a period of 38 h to monitor the evolution of Mn2+-induced signal enhancement across the ventral tegmental area, the medial forebrain bundle (MFB), and the striatum. The MDMA-induced loss of serotonin transporters was clearly evidenced by immunohistological staining consistent with the Mn2+-induced signal enhancement observed across the MFB and striatum. MEMRI successfully revealed the disruption of the serotonergic raphe-striatal projections and the variable effect of MDMA on the kinetics of Mn2+ accumulation in the MFB and striatum. PMID- 26378924 TI - Caged Fluoride: Photochemistry and Applications of 4-Hydroxyphenacyl Fluoride. AB - The quantitative, efficient (Phi = 0.8) photorelease of the fluoride ion upon UV irradiation in aqueous media is introduced. The 4-hydroxyphenacyl chromophore is simultaneously transformed into UV-transparent 4-hydroxyphenylacetate via a photo Favorskii rearrangement. The application of this process is demonstrated by photoinduced etching of mica and silicon by AFM. PMID- 26378925 TI - Intra- and Inter-Task Reliability of Spatial Attention Measures in Pseudoneglect. AB - Healthy young adults display a leftward asymmetry of spatial attention ("pseudoneglect") that has been measured with a wide range of different tasks. Yet at present there is a lack of systematic evidence that the tasks commonly used in research today are i) stable measures over time and ii) provide similar measures of spatial bias. Fifty right-handed young adults were tested on five tasks (manual line bisection, landmark, greyscales, gratingscales and lateralised visual detection) on two different days. All five tasks were found to be stable measures of bias over the two testing sessions, indicating that each is a reliable measure in itself. Surprisingly, no strongly significant inter-task correlations were found. However, principal component analysis revealed left right asymmetries to be subdivided in 4 main components, namely asymmetries in size judgements (manual line bisection and landmark), luminance judgements (greyscales), stimulus detection (lateralised visual detection) and judgements of global/local features (manual line bisection and grating scales). The results align with recent research on hemispatial neglect which conceptualises the condition as multi-component rather than a single pathological deficit of spatial attention. We conclude that spatial biases in judgment of visual stimulus features in healthy adults (e.g., pseudoneglect) is also a multi-component phenomenon that may be captured by variations in task demands which engage task dependent patterns of activation within the attention network. PMID- 26378926 TI - Long Term Development of Gut Microbiota Composition in Atopic Children: Impact of Probiotics. AB - INTRODUCTION: Imbalance of the human gut microbiota in early childhood is suggested as a risk factor for immune-mediated disorders such as allergies. With the objective to modulate the intestinal microbiota, probiotic supplementation during infancy has been used for prevention of allergic diseases in infants, with variable success. However, not much is known about the long-term consequences of neonatal use of probiotics on the microbiota composition. The aim of this study was to assess the composition and microbial diversity in stool samples of infants at high-risk for atopic disease, from birth onwards to six years of age, who were treated with probiotics or placebo during the first year of life. METHODS: In a double-blind, randomized, placebo-controlled trial, a probiotic mixture consisting of B. bifidum W23, B. lactis W52 and Lc. Lactis W58 (Ecologic(r) Panda) was administered to pregnant women during the last 6 weeks of pregnancy and to their offspring during the first year of life. During follow-up, faecal samples were collected from 99 children over a 6-year period with the following time points: first week, second week, first month, three months, first year, eighteen months, two years and six years. Bacterial profiling was performed by IS pro. Differences in bacterial abundance and diversity were assessed by conventional statistics. RESULTS: The presence of the supplemented probiotic strains in faecal samples was confirmed, and the probiotic strains had a higher abundance and prevalence in the probiotic group during supplementation. Only minor and short term differences in composition of microbiota were found between the probiotic and placebo group and between children with or without atopy. The diversity of Bacteroidetes was significantly higher after two weeks in the placebo group, and at the age of two years atopic children had a significantly higher Proteobacteria diversity (p < 0.05). Gut microbiota development continued between two and six years, whereby microbiota composition at phylum level evolved more and more towards an adult-like configuration. CONCLUSION: Perinatal supplementation with Ecologic(r) Panda, to children at high-risk for atopic disease, had minor effects on gut microbiota composition during the supplementation period. No long lasting differences were identified. Regardless of intervention or atopic disease status, children had a shared microbiota development over time determined by age that continued to develop between two and six years. PMID- 26378927 TI - Des-Aspartate-Angiotensin I Attenuates Mortality of Mice Exposed to Gamma Radiation via a Novel Mechanism of Action. AB - ACE inhibitors and ARBs (angiotensin receptor blockers) have been shown to attenuate radiation injuries in animal models of lethal gamma irradiation. These two classes of drug act by curtailing the actions of angiotensin II-linked inflammatory pathways that are up-regulated during gamma radiation in organ systems such as the brain, lung, kidney, and bone marrow. ACE inhibitors inhibit ACE and attenuate the formation of angiotensin II from angiotensin I; ARBs block the angiotensin AT1 receptor and attenuate the actions of angiotensin II that are elicited through the receptor. DAA-I (des-aspartate-angiotensin I), an orally active angiotensin peptide, also attenuates the deleterious actions of angiotensin II. It acts as an agonist on the angiotensin AT1 receptor and elicits responses that oppose those of angiotensn II. Thus, DAA-I was investigated for its anticipated radioprotection in gamma irradiated mice. DAA-I administered orally at 800 nmole/kg/day for 30 days post exposure (6.4 Gy) attenuated the death of mice during the 30-day period. The attenuation was blocked by losartan (50 nmole/kg/day, i.p.) that was administered sequential to DAA-I administration. This shows that the radioprotection was mediated via the angiotensin AT1 receptor. Furthermore, the radioprotection correlated to an increase in circulating PGE2 of surviving animals, and this suggests that PGE2 is involved in the radioprotection in DAA-I-treated mice. At the hematopoietic level, DAA-I significantly improved two syndromes of myelosuppression (leucopenia and lymphocytopenia), and mice pre-treated with DAA-I prior to gamma irradiation showed significant improvement in the four myelodysplastic syndromes that were investigated, namely leucopenia, lymphocytopenia, monocytopenia and thrombocytopenia. Based on the known ability of PGE2 to attenuate the loss of functional hematopoietic stem and progenitor cells in radiation injury, we hypothesize that PGE2 mediated the action of DAA-I. DAA-I completely attenuated the increase in circulating level of two inflammatory cytokines, TNFalpha and IL 6, in irradiated mice; and this shows that DAA-I exerted additional anti inflammatory actions, which could also have contributed to its radioprotection. These findings show that DAA-I acts via a novel mechanism of action on the angiotensin AT1 receptor to specifically release PGE2, which mediates radioprotection in the gamma irradiated mice. PMID- 26378929 TI - Correction: The Role of ExoS in Dissemination of Pseudomonas aeruginosa during Pneumonia. PMID- 26378928 TI - Recovery of Corneal Endothelial Cells from Periphery after Injury. AB - BACKGROUND: Wound healing of the endothelium occurs through cell enlargement and migration. However, the peripheral corneal endothelium may act as a cell resource for the recovery of corneal endothelium in endothelial injury. AIM: To investigate the recovery process of corneal endothelial cells (CECs) from corneal endothelial injury. METHODS: Three patients with unilateral chemical eye injuries, and 15 rabbit eyes with corneal endothelial chemical injuries were studied. Slit lamp examination, specular microscopy, and ultrasound pachymetry were performed immediately after chemical injury and 1, 3, 6, and 9 months later. The anterior chambers of eyes from New Zealand white rabbits were injected with 0.1 mL of 0.05 N NaOH for 10 min (NaOH group). Corneal edema was evaluated at day 1, 7, and 14. Vital staining was performed using alizarin red and trypan blue. RESULTS: Specular microscopy did not reveal any corneal endothelial cells immediately after injury. Corneal edema subsided from the periphery to the center, CEC density increased, and central corneal thickness decreased over time. In the animal study, corneal edema was greater in the NaOH group compared to the control at both day 1 and day 7. At day 1, no CECs were detected at the center and periphery of the corneas in the NaOH group. Two weeks after injury, small, hexagonal CECs were detected in peripheral cornea, while CECs in mid-periphery were large and non-hexagonal. CONCLUSIONS: CECs migrated from the periphery to the center of the cornea after endothelial injury. The peripheral corneal endothelium may act as a cell resource for the recovery of corneal endothelium. PMID- 26378930 TI - Lewis acidity of Si6Cl12 and its role as convenient SiCl2 source. AB - The free cyclohexasilane Si6Cl12 (1) was obtained in 66% yield from the corresponding Cl(-) diadduct [nBu4N]2[1.2Cl] and AlCl3 in C6H6. The substituted cyclohexasilane 1,1-(Cl3Si)2Si6Cl10 (2), however, cannot be liberated from [nBu4N]2[2.2Cl] under comparable reaction conditions. Instead, a mixture of several products was obtained, from which the oligosilane Si19Cl36 (3) crystallized in low yields. X-ray crystallography revealed 3 to consist of two Si5 rings, bridged by one silicon atom. Compound 1 possesses Lewis acidic sites above and below the ring centroid. Competition experiments reveal that their corresponding acid strengths are comparable to that of BCl3. The reaction of 1 with 6 equiv of 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene (Idipp) leads to a complete breakdown of the cyclic scaffold and furnishes the dichlorosilylene adduct Idipp-SiCl2. PMID- 26378931 TI - Roberts Prize for the best paper published in 2014. PMID- 26378932 TI - Correction: Motion Tracker: Camera-Based Monitoring of Bodily Movements Using Motion Silhouettes. PMID- 26378934 TI - Correction: The Evolution of Fungal Metabolic Pathways. PMID- 26378933 TI - Deletion of Chromosomal Region 8p21 Confers Resistance to Bortezomib and Is Associated with Upregulated Decoy TRAIL Receptor Expression in Patients with Multiple Myeloma. AB - Loss of the chromosomal region 8p21 negatively effects survival in patients with multiple myeloma (MM) that undergo autologous stem cell transplantation (ASCT). In this study, we aimed to identify the immunological and molecular consequences of del(8)(p21) with regards to treatment response and bortezomib resistance. In patients receiving bortezomib as a single first line agent without any high-dose therapy, we have observed that patients with del(8)(p21) responded poorly to bortezomib with 50% showing no response while patients without the deletion had a response rate of 90%. In vitro analysis revealed a higher resistance to bortezomib possibly due to an altered gene expression profile caused by del(8)(p21) including genes such as TRAIL-R4, CCDC25, RHOBTB2, PTK2B, SCARA3, MYC, BCL2 and TP53. Furthermore, while bortezomib sensitized MM cells without del(8)(p21) to TRAIL/APO2L mediated apoptosis, in cells with del(8)(p21) bortezomib failed to upregulate the pro-apoptotic death receptors TRAIL-R1 and TRAIL-R2 which are located on the 8p21 region. Also expressing higher levels of the decoy death receptor TRAIL-R4, these cells were largely resistant to TRAIL/APO2L mediated apoptosis. Corroborating the clinical outcome of the patients, our data provides a potential explanation regarding the poor response of MM patients with del(8)(p21) to bortezomib treatment. Furthermore, our clinical analysis suggests that including immunomodulatory agents such as Lenalidomide in the treatment regimen may help to overcome this negative effect, providing an alternative consideration in treatment planning of MM patients with del(8)(p21). PMID- 26378935 TI - Ionic liquids in bioanalysis. AB - Ionic liquids (ILs) are entirely composed of ions and they possess fascinating properties, including low volatility, tunable viscosity, miscibility and electrolytic conductivity, which make them promising alternatives to traditional organic solvents used in sample preparation. The recent surge in the number of publications clearly indicates an increasing interest of the analytical and bioanalytical community toward these exciting and unique solvents. This article highlights the recent advances in the use of ILs as extraction solvents, as materials for separation and preconcentration in chromatographic techniques, and as matrices in mass spectrometric techniques for bioassays in biocomplex samples. We also briefly discuss the potential applications of ILs in biocatalysis. PMID- 26378936 TI - An update on solid phase-supported liquid extraction. AB - Solid phase-supported liquid extraction (SLE) is a technique almost 40 years old being rediscovered in the last few years due to its simplicity, optimal for automation and giving very clean extracts with minimal matrix effects when analyzed by techniques like HPLC-MS/MS, GC-MS/MS, CE-MS/MS. In the next paragraphs the evolution of SLE, according to literature, will be presented first, followed by some considerations on the SLE material now available and a typical protocol of work. To conclude, considerations based on the author's practical experiences with SLE will be done, as well as few remarks on potential future areas of SLE development. PMID- 26378937 TI - Molecularly imprinted polymers for on-line extraction techniques. AB - Recent years have seen an increasing interest in the use of molecularly imprinted polymers (MIPs) as a sorbent for different extraction methods and this is due to its high selectivity. The MIP is designed to show specificity for the analyte of interest. Moreover, MIPs show physical robustness, resistance to high temperatures and pressures, and stability in the presence of acids, bases and a wide range of organic solvents. In the present article, various novel sample preparation techniques which MIPs applied as sorbent and on-line connected with analytical instruments were highlighted and discussed. The future aspects of MIPs as well were described. PMID- 26378938 TI - The Effect of Age, Parity and Body Mass Index on the Efficacy, Safety, Placement and User Satisfaction Associated With Two Low-Dose Levonorgestrel Intrauterine Contraceptive Systems: Subgroup Analyses of Data From a Phase III Trial. AB - OBJECTIVE: Two low-dose levonorgestrel intrauterine contraceptive systems (LNG IUSs; total content 13.5 mg [average approx. 8 MUg/24 hours over the first year; LNG-IUS 8] and total content 19.5 mg [average approx. 13 MUg/24 hours over the first year; LNG-IUS 13]) have previously been shown to be highly effective (3 year Pearl Indices: 0.33 and 0.31, respectively), safe and well tolerated. The present subgroup analyses evaluated whether or not outcomes were affected by parity, age (18-25 vs 26-35 years), or body mass index (BMI, <30 vs >=30 kg/m2). METHODS: Nulliparous and parous women aged 18-35 years with regular menstrual cycles (21-35 days) requesting contraception were randomized to 3 years of LNG IUS 8 or LNG-IUS 13 use. RESULTS: In the LNG-IUS 8 and LNG-IUS 13 groups, 1432 and 1452 women, respectively, had a placement attempted and were included in the full analysis set; 39.2%, 39.2% and 17.1% were 18-25 years old, nulliparous and had a BMI >=30 kg/m2, respectively. Both systems were similarly effective regardless of age, parity or BMI; the subgroup Pearl Indices had widely overlapping 95% confidence intervals. Placement of LNG-IUS 8 and LNG-IUS 13 was easier (p < 0.0001) and less painful (p < 0.0001) in women who had delivered vaginally than in women who had not. The complete/partial expulsion rate was 2.2 4.2% across all age and parity subgroups and higher in parous than in nulliparous women (p = 0.004). The incidence of pelvic inflammatory disease was 0.1-0.6% across all age and parity subgroups: nulliparous and younger women were not at higher risk than parous and older women, respectively. The ectopic pregnancy rate was 0.3-0.4% across all age and parity subgroups. Across all age and parity subgroups, the 3-year completion rate was 50.9-61.3% for LNG-IUS 8 and 57.9-61.1% for LNG-IUS 13, and was higher (p = 0.0001) among older than younger women in the LNG-IUS 8 group only. CONCLUSIONS: LNG-IUS 8 and LNG-IUS 13 were highly effective, safe and well tolerated regardless of age or parity. TRIAL REGISTRATION: Clinical trials.gov NCT00528112. PMID- 26378940 TI - Redefining the Breast Cancer Exosome Proteome by Tandem Mass Tag Quantitative Proteomics and Multivariate Cluster Analysis. AB - Exosomes are microvesicles of endocytic origin constitutively released by multiple cell types into the extracellular environment. With evidence that exosomes can be detected in the blood of patients with various malignancies, the development of a platform that uses exosomes as a diagnostic tool has been proposed. However, it has been difficult to truly define the exosome proteome due to the challenge of discerning contaminant proteins that may be identified via mass spectrometry using various exosome enrichment strategies. To better define the exosome proteome in breast cancer, we incorporated a combination of Tandem Mass-Tag (TMT) quantitative proteomics approach and Support Vector Machine (SVM) cluster analysis of three conditioned media derived fractions corresponding to a 10 000g cellular debris pellet, a 100 000g crude exosome pellet, and an Optiprep enriched exosome pellet. The quantitative analysis identified 2 179 proteins in all three fractions, with known exosomal cargo proteins displaying at least a 2 fold enrichment in the exosome fraction based on the TMT protein ratios. Employing SVM cluster analysis allowed for the classification 251 proteins as "true" exosomal cargo proteins. This study provides a robust and vigorous framework for the future development of using exosomes as a potential multiprotein marker phenotyping tool that could be useful in breast cancer diagnosis and monitoring disease progression. PMID- 26378939 TI - Patient Empowerment Improved Perioperative Quality of Care in Cancer Patients Aged >= 65 Years - A Randomized Controlled Trial. AB - PURPOSE: This randomized controlled, clinical prospective interventional trial was aimed at exploring the effect of patient empowerment on short- and long-term outcomes after major oncologic surgery in elderly cancer patients. METHODS: This trial was performed from February 2011 to January 2014 at two tertiary medical centers in Germany. The study included patients aged 65 years and older undergoing elective surgery for gastro-intestinal, genitourinary, and thoracic cancer. The patients were randomly assigned to the intervention group, i.e. patient empowerment through information booklet and diary keeping, or to the control group, which received standard care. Randomization was done by block randomization in blocks of four in order of enrollment. The primary outcome were 1,postoperative length of hospital stay (LOS) and 2. long-term global health related quality of life (HRQoL) one year postoperatively. HRQoL was assessed using the EORTC QLQ C30 questionnaire. Secondary outcomes encompassed postoperative stress and complications. Further objectives were the identification of predictors of LOS, and HRQoL at 12 months. RESULTS: Overall 652 patients were included. The mean age was 72 +/- 4.9 years, and the majority of patients were male (68.6%, n = 447). The ^median of postoperative length of stay was 9 days (IQR 7-14 day). There were no significant differences between the intervention and the control groups in postoperative LOS (p = 0.99) or global HRQoL after one year (women: p = 0.54, men: p = 0.94). While overall complications and major complications occurred in 74% and 24% of the cases, respectively, frequency and severity of complications did not differ significantly between the groups. Patients in the intervention group reported significantly less postoperative pain (p = 0.03) than the control group. Independent predictors for LOS were identified as severity of surgery, length of anesthesia, major postoperative complications, nutritional state, and pre operative physical functional capacity measured by the Timed Up and Go-test by multiple robust regressions. CONCLUSION: Patient empowerment through information booklet and diary keeping did not shorten the postoperative LOS in elderly onco surgical patients, but improved quality of care regarding postoperative pain. Postoperative length of stay is influenced by pre-operative nutritional state, pre-operative functional impairment, severity of surgery, and length of anesthesia. TRIAL REGISTRATION: Clinicaltrials.gov. Identifier NCT01278537. PMID- 26378941 TI - Ribavirin concentration determines treatment success of first-generation DAA based chronic HCV therapy. AB - BACKGROUND: Monitoring ribavirin concentrations during hepatitis C treatment with dual therapy can help optimize treatment response and minimize anaemia. A defined therapeutic range for ribavirin during direct-acting antiviral-based therapies is lacking. This analysis explores whether a therapeutic range for ribavirin concentrations can be defined in patients treated with boceprevir- or telaprevir based triple therapies. METHODS: Treatment-naive patients from ADVANCE, ILLUMINATE, OPTIMIZE and SPRINT-2, and treatment-experienced patients from RESPOND-2 were included. Multivariable logistic regression analyses were performed to evaluate whether ribavirin concentrations were an independent predictor of sustained virological response or anaemia. Optimal cutoff values and the percentage of patients within the proposed therapeutic range were determined, along with the associated chance of response. RESULTS: Overall, 1,502 patients were included. In both regimens, ribavirin concentrations were significantly associated with anaemia (haemoglobin level <10 g/dl) at all time points (1.75 < odds ratio [OR] <2.45) and sustained virological response was associated with ribavirin concentrations at week 8 (OR=1.43 for telaprevir and 1.78 for boceprevir). A therapeutic range for ribavirin at week 8 of 2.2-3.5 mg/l was defined for telaprevir treatment. Of the 48% of patients with a concentration within this range, 81% achieved sustained virological response and only 5.1% reported anaemia. For boceprevir treatment, the week 8 optimal range was defined as 2.2-3.6 mg/l and 50% of patients had a concentration within this range, of whom 69% achieved sustained virological response and 46% developed anaemia. CONCLUSIONS: We established the therapeutic range for ribavirin in boceprevir- and telaprevir-based therapy that balances safety and efficacy. PMID- 26378942 TI - The Effects of Breaking up Prolonged Sitting Time: A Review of Experimental Studies. AB - INTRODUCTION: Prolonged time spent in sedentary behaviors (i.e., activities performed while sitting or reclining) has been consistently shown as an independent risk factor for increased cardiometabolic risk and all-cause mortality, whereas breaking up sedentary time is associated with improved cardiometabolic profile. However, there is still great controversy with the respect to what would be the optimal or minimum type, intensity, and frequency of physical activity necessary to revenue such positive outcomes in different populations. OBJECTIVE: In this review, we aimed to discuss the available evidence from prospective experimental studies regarding the beneficial effects of breaking up prolonged sitting time on cardiometabolic risk factors, and the influence of intensity, frequency, and volume of the physical activity replacing sitting. METHODS: A structured computer-based search on the electronic databases PUBMED and SCOPUS was independently conducted by two researchers. Only prospective intervention studies (controlled and uncontrolled) evaluating the effects of explicitly replacing sitting time with physical activity (including standing) on metabolic parameters as outcomes were included. RESULTS: Seventeen studies were included in the review. DISCUSSION: The currently available prospective experimental studies do advocate that breaking up sitting time and replacing it with light-intensity ambulatory physical activity and standing may be a stimulus sufficient enough to induce acute favorable changes in the postprandial metabolic parameters in physically inactive and type 2 diabetic subjects, whereas a higher intensity or volume seems to be more effective in rendering such positive outcomes in young habitually physically active subjects. CONCLUSION: Prospective experimental studies provide considerable evidence of the positive effects of breaking up prolonged time spent sitting on metabolic outcomes. However, it seems that the type, intensity, and frequency of physical activity necessary to effectively counteract the detrimental effects of prolonged sitting may differ according to the subjects' characteristics, especially with respect to the subjects' habitual physical activity level. PMID- 26378944 TI - Sedentary and Active Time in Toddlers with and without Cerebral Palsy. AB - INTRODUCTION/PURPOSE: To evaluate differences in sedentary time and compare levels of physical activity and sedentary behavior to the Australian physical activity recommendations between toddlers with cerebral palsy (CP) according to functional capacity (Gross Motor Function Classification System [GMFCS]) and age matched children with typical development (CTD). METHODS: Children (2.4 +/- 0.5 yr old) were split into CTD (n = 20), GMFCS I-II (n = 32), GMFCS III (n = 14), and GMFCS IV-V (n = 12) groups and wore a triaxial ActiGraph(r) for 3 d. Validated cut points were applied to identify sedentary and active time and the number and duration of sedentary bouts and breaks for each group. Analysis of variance (ANOVA) with post hoc testing, chi-square analysis, and the Fisher exact test were used to compare groups. RESULTS: No difference between the CTD group (49%) and GMFCS I-II group (52%) was found for sedentary time as a percentage of wear time. The GMFCS III group was more sedentary than both these groups (62%, P < 0.05). The GMFCS IV-V group was more sedentary than all the other groups (74%, P < 0.05). The CTD group and GMFCS I-II group was more likely to spend 180 min or longer in active play on all 3 d than the GMFCS IV-V group (P < 0.05). The GMFCS IV-V group was more likely to have sedentary bouts >=60 min or longer than all other groups (P < 0.05). CONCLUSION: Differences in sedentary behavior between the CTD and mildly impaired children with CP (GMFCS I-II) are not evident in the toddler years. Children with moderate-to-severe functional impairment are progressively more sedentary and less likely to meet physical activity guidelines. Further research into the health implications of high levels of sedentary behavior in toddlers is required. PMID- 26378943 TI - The Potential Impact of Displacing Sedentary Time in Adults with Type 2 Diabetes. AB - PURPOSE: Sedentary time, in particular, prolonged unbroken sedentary time, is detrimental to health and displaces time spent in either light or moderate intensity physical activity. This cross-sectional study aimed to identify the potential impact of reallocating time from sedentary behaviors to more active behaviors on measures of body composition and metabolic health in people with type 2 diabetes. METHODS: Participants were 519 adults with newly diagnosed type 2 diabetes who had been recruited to the Early Activity in Diabetes (Early ACTID) randomized controlled trial. Waist-worn accelerometers were used to obtain objective measurement of sedentary time, light physical activity (LPA), and moderate-to-vigorous physical activity (MVPA) at baseline alongside clinical measurements and fasting blood samples to determine cholesterol, triglycerides, HOMA-IR, and glucose. Isotemporal substitution modeling was performed to determine the potential impact of reallocating 30 min of sedentary time accumulated in a single bout (long bout) with 30 min of interrupted sedentary time, LPA, or MVPA. RESULTS: Sedentary time accounted for 65% of the waking day, of which 45% was accumulated in prolonged (>=30 min) bouts. Reallocation of 30 min of long-bout sedentary time with 30 min of short-bout sedentary time was associated with lower body mass index (BMI) (adjusted beta, -0.60; 95% confidence interval [CI], -1.00, -0.21) and waist circumference (WC) (adjusted beta, -1.16; 95% CI, -2.08, -0.25). Stronger effects were seen for LPA and MVPA. Reallocation of 30 min of long-bout sedentary time with LPA was associated with higher HDL cholesterol (adjusted beta, 0.02; 95% CI, 0.00-0.03 mmol.L). CONCLUSIONS: Encouraging adults with newly diagnosed type 2 diabetes to break up prolonged periods of sedentary time may be an effective strategy for improving body composition and metabolic health. PMID- 26378945 TI - Motor Development and Physical Activity: A Longitudinal Discordant Twin-Pair Study. AB - INTRODUCTION: Previous longitudinal research suggests that motor proficiency in early life predicts physical activity in adulthood. Familial effects including genetic and environmental factors could explain the association, but no long-term follow-up studies have taken into account potential confounding by genetic and social family background. The present twin study investigated whether childhood motor skill development is associated with leisure-time physical activity levels in adulthood independent of family background. METHODS: Altogether, 1550 twin pairs from the FinnTwin12 study and 1752 twin pairs from the FinnTwin16 study were included in the analysis. Childhood motor development was assessed by the parents' report of whether one of the co-twins had been ahead of the other in different indicators of motor skill development in childhood. Leisure-time physical activity (MET.h.d) was self-reported by the twins in young adulthood and adulthood. Statistical analyses included conditional and ordinary linear regression models within twin pairs. RESULTS: Using all activity-discordant twin pairs, the within-pair difference in a sum score of motor development in childhood predicted the within-pair difference in the leisure-time physical activity level in young adulthood (P < 0.001). Within specific motor development indicators, learning to stand unaided earlier in infancy predicted higher leisure time MET values in young adulthood statistically significantly in both samples (FinnTwin12, P = 0.02; and FinnTwin16, P = 0.001) and also in the pooled data set of the FinnTwin12 and FinnTwin16 studies (P < 0.001). Having been more agile than the co-twin as a child predicted higher leisure-time MET values up to adulthood (P = 0.03). CONCLUSIONS: More advanced childhood motor development is associated with higher leisure-time MET values in young adulthood at least partly independent of family background in both men and women. PMID- 26378946 TI - Combined Training Reduces Subclinical Inflammation in Obese Middle-Age Men. AB - PURPOSE: We investigated the effects of 24 wk of combined training on proinflammatory and anti-inflammatory markers associated with obesity in obese middle-age men. METHODS: Thirty obese men (48.73 +/- 1.04 yr; body mass index, 31.00 +/- 0.29 kg.m) underwent 24 wk of combined training [CT (N = 17), aerobic (50%-85% of VO2peak) and resistance (6-10 maximum repetition [RM]) training)] three times per week, 60 min per session, or a control group (N = 13). Anthropometric measures, maximal strength for leg press and bench press, peak oxygen uptake (VO2peak) and serum concentrations of C-reactive protein (CRP), tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), IL-10, IL-15, resistin, leptin, and adiponectin were determined before (M1) and after 8 (M2), 16 (M3), and 24 (M4) wk of the experimental design. RESULTS: Significant increases were observed in the maximal strength for bench press and leg press, VO2peak, and serum concentrations of adiponectin and IL-15 for CT. Concomitantly, significant decreases were observed in percentage body fat and serum concentrations of CRP, resistin, and leptin for CT after the experimental period. CONCLUSION: Twenty-four weeks of moderate- to high-intensity CT reduced markers of subclinical inflammation associated with obesity and improved insulin resistance and functional capabilities of obese middle-age men, regardless of dietary intervention and weight loss. PMID- 26378947 TI - Nongrafted Skin Area Best Predicts Exercise Core Temperature Responses in Burned Humans. AB - Grafted skin impairs heat dissipation, but it is unknown to what extent this affects body temperature during exercise in the heat. PURPOSE: We examined core body temperature responses during exercise in the heat in a group of individuals with a large range of grafts covering their body surface area (BSA; 0%-75%). METHODS: Forty-three individuals (19 females) were stratified into groups based on BSA grafted: control (0% grafted, n = 9), 17%-40% (n = 19), and >40% (n = 15). Subjects exercised at a fixed rate of metabolic heat production (339 +/- 70 W; 4.3 +/- 0.8 W.kg) in an environmental chamber set at 40 degrees C, 30% relative humidity for 90 min or until exhaustion (n = 8). Whole-body sweat rate and core temperatures were measured. RESULTS: Whole-body sweat rates were similar between the groups (control: 14.7 +/- 3.4 mL.min, 17%-40%: 12.6 +/- 4.0 mL.min; and >40%: 11.7 +/- 4.4 mL.min; P > 0.05), but the increase in core temperature at the end of exercise in the >40% BSA grafted group (1.6 degrees C +/- 0.5 degrees C) was greater than the 17%-40% (1.2 degrees C +/- 0.3 degrees C) and control (0.9 degrees C +/- 0.2 degrees C) groups (P < 0.05). Absolute BSA of nongrafted skin (expressed in square meters) was the strongest independent predictor of the core temperature increase (r = 0.41). When regrouping all subjects, individuals with the lowest BSA of nongrafted skin (<1.0 m) had greater increases in core temperature (1.6 degrees C +/- 0.5 degrees C) than those with more than 1.5 m nongrafted skin (1.0 degrees C +/- 0.3 degrees C; P < 0.05). CONCLUSIONS: These data imply that individuals with grafted skin have greater increases in core temperature when exercising in the heat and that the magnitude of this increase is best explained by the amount of nongrafted skin available for heat dissipation. PMID- 26378949 TI - Validity and Reproducibility of a New Treadmill Protocol: The Fitkids Treadmill Test. AB - PURPOSE: This study aimed to investigate the validity and reproducibility of a new treadmill protocol in healthy children and adolescents: the Fitkids Treadmill Test (FTT). METHODS: Sixty-eight healthy children and adolescents (6-18 yr) were randomly divided into a validity group (14 boys and 20 girls; mean +/- SD age, 12.9 +/- 3.6 yr) that performed the FTT and Bruce protocol, both with respiratory gas analysis within 2 wk, and a reproducibility group (19 boys and 15 girls; mean +/- SD age, 13.5 +/- 3.5 yr) that performed the FTT twice within 2 wk. A subgroup of 21 participants within the reproducibility group performed both FTT with respiratory gas analysis. Time to exhaustion (TTE) was the main outcome of the FTT. RESULTS: VO2peak measured during the FTT showed excellent correlation with VO2peak measured during the Bruce protocol (r = 0.90; P < 0.01). Backward multiple regression analysis provided the following prediction equations for VO2peak (L.min) for boys and girls, respectively: VO2peak FTT = -0.748 + (0.117 * TTEFTT) + (0.032 * body mass) + 0.263, and VO2peak FTT = -0.748 + (0.117 * TTEFTT) + (0.032 * body mass) [R = 0.935; SEE = 0.256 L.min]. Cross-validation of the regression model showed an R value of 0.76. Reliability statistics for the FTT showed an intraclass correlation coefficient of 0.985 (95% confidence interval, 0.971-0.993; P < 0.001) for TTE. Bland-Altman analysis showed a mean bias of -0.07 min, with limits of agreement between +1.30 and -1.43 min. CONCLUSIONS: Results suggest that the FTT is a useful treadmill protocol with good validity and reproducibility in healthy children and adolescents. Exercise performance on the FTT and body mass can be used to adequately predict VO2peak when respiratory gas analysis is not available. PMID- 26378950 TI - Influence of Microbubbles on Free Radical Generation by Ultrasound in Aqueous Solution: Dependence of Ultrasound Frequency. AB - The influence of microbubbles on sonochemical efficiencies has been investigated under 28, 45, and 100 kHz ultrasound irradiation. For the 28 and 100 kHz ultrasound frequencies, microbubbles suppressed the I3(-) formation from KI solution as well as the 7-hydroxycoumarin formation from coumarin solution caused by the ultrasonic irradiation. On the other hand, for the 45 kHz ultrasound frequency, microbubbles enhanced the I3(-) formation from KI solution as well as 7-hydroxycoumarin formation from coumarin solution caused by the ultrasonic irradiation. Detection of H2O2 after the irradiation of ultrasound in the presence or absence of microbubbles was also performed, and it was found that H2O2 formation was enhanced only when microbubbles were introduced under the 45 kHz ultrasonic irradiation, which was in good agreement with the results of KI oxidation dosimetry measurements and of coumarin fluorescent probe measurements. Based on these present results, plausible mechanisms that explain the dependence of the ultrasound frequency on the enhancement and suppression of free radical formation in the presence of MBs were proposed. PMID- 26378948 TI - Quantification of the Balance Error Scoring System with Mobile Technology. AB - PURPOSE: The aim of this project was to develop a biomechanically based quantification of the Balance Error Scoring System (BESS) using data derived from the accelerometer and gyroscope of a mobile tablet device. METHODS: Thirty-two healthy young adults completed the BESS while an iPad was positioned at the sacrum. Data from the iPad were compared to position data gathered from a three dimensional motion capture system. Peak-to-peak (P2P), normalized path length (NPL), and root mean squared (RMS) were calculated for each system and compared. Additionally, a 95% ellipsoid volume, iBESS volume, was calculated using center of mass (CoM) movements in the anteroposterior (AP), mediolateral (ML), and trunk rotation planes of movement to provide a comprehensive, 3D metric of postural stability. RESULTS: Across all kinematic outcomes, data from the iPad were significantly correlated with the same outcomes derived from the motion capture system (rho range, 0.37-0.94; P < 0.05). The iBESS volume metric was able to detect a difference in postural stability across stance and surface, showing a significant increase in volume in increasingly difficult conditions, whereas traditional error scoring was not as sensitive to these factors. CONCLUSIONS: The kinematic data provided by the iPad are of sufficient quality relative to motion capture data to accurately quantify postural stability in healthy young adults. The iBESS volume provides a more sensitive measure of postural stability than error scoring alone, particularly in conditions 1 and 4, which often suffer from floor effects, and condition 5, which can experience ceiling effects. The iBESS metric is ideally suited for clinical and in the field applications in which characterizing postural stability is of interest. PMID- 26378951 TI - The three-legged stool: Balancing the PA value stream. PMID- 26378952 TI - Correction: Is there an intramolecular hydrogen bond in 2-halophenols? A theoretical and spectroscopic investigation. AB - Correction for 'Is there an intramolecular hydrogen bond in 2-halophenols? A theoretical and spectroscopic investigation' by Michael H. Abraham et al., Phys. Chem. Chem. Phys., 2015, DOI: 10.1039/c5cp04061b. PMID- 26378953 TI - Effects of prasugrel pretreatment on angiographic myocardial perfusion parameters in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention. AB - OBJECTIVE: Prasugrel is a third-generation thienopyridine, with significant pharmacodynamic and clinical advantages over clopidogrel. There are few data on the effects of prasugrel therapy, as compared with clopidogrel, in terms of perfusion during percutaneous coronary intervention (PCI), in patients with ST elevation myocardial infarction (STEMI). METHODS: A total of 128 patients with STEMI, pretreated with prasugrel 60 mg loading dose (mean age=55.9+/-9.1; 10.9% were women and 18.0% had diabetes), were compared with 128 propensity-matched patients pretreated with clopidogrel 600 mg (mean age=58.7+/-10.7; 10.2% were women and 19.5% had diabetes) for the primary endpoint of thrombolysis in myocardial infarction (TIMI) flow and myocardial blush grade at completion of the PCI. Secondary endpoints included the combined sum of major adverse events: death, reinfarction or target vessel revascularization at 1 year. RESULTS: Mean TIMI flow grade pre-PCI was similar between the two groups (1.31+/-1.3 in the prasugrel group and 1.30+/-1.2 in the clopidogrel group, P=0.96). However, after intervention, it was higher in the prasugrel group (2.94+/-0.24 vs. 2.84+/-0.37, respectively, P=0.016), as was myocardial blush (2.70+/-0.76 vs. 2.31+/-0.52, respectively, P<0.001). The percentage of TIMI 3 after intervention was also higher in the prasugrel group (97.70 vs. 90.60%, P=0.02). The combined rate of major adverse events at 1 year (8.7 vs. 11.6%, P=0.11), as well as total mortality (3.1+/-5.6 vs. 4.7+/-9.1%, P=0.52), did not differ between the two groups. CONCLUSION: In patients with STEMI undergoing primary PCI, pretreatment with prasugrel resulted in better angiographic perfusion results, as compared with pretreatment with clopidogrel. PMID- 26378954 TI - Functionally Graded Interfaces: Role and Origin of Internal Electric Field and Modulated Electrical Response. AB - We report the tunable electrical response in functionally graded interfaces in lead-free ferroelectric thin films. Multilayer thin film graded heterostructures were synthesized on platinized silicon substrate with oxide layers of varying thickness. Interestingly, the graded heterostructure thin films exhibited shift of the hysteresis loops on electric field and polarization axes depending upon the direction of an applied bias. A diode-like characteristics was observed in current-voltage behavior under forward and reverse bias. This modulated electrical behavior was attributed to the perturbed dynamics of charge carriers under internal bias (self-bias) generated due to the increased skewness of the potential wells. The cyclic sweeping of voltage further demonstrated memristor like current-voltage behavior in functionally graded heterostructure devices. The presence of an internal bias assisted the generation of photocurrent by facilitating the separation of photogenerated charges. These novel findings provide opportunity to design new circuit components for the next generation of microelectronic device architectures. PMID- 26378955 TI - DMSA-Coated Iron Oxide Nanoparticles Greatly Affect the Expression of Genes Coding Cysteine-Rich Proteins by Their DMSA Coating. AB - The dimercaptosuccinic acid (DMSA) was widely used to coat iron oxide nanoparticles (FeNPs); however, its intracellular cytotoxicity remains to be adequately elucidated. This study analyzed the differentially expressed genes (DEGs) in four mammalian cells treated by a DMSA-coated magnetite FeNP at various doses at different times. The results revealed that about one-fourth of DEGs coded cysteine-rich proteins (CRPs) in all cells under each treatment, indicating that the nanoparticles greatly affected the expressions of CRP-coding genes. Additionally, about 26% of CRP-coding DEGs were enzyme genes in all cells, indicating that the nanoparticles greatly affected the expression of enzyme genes. Further experiments with the nanoparticles and a polyethylenimine (PEI) coated magnetite FeNP revealed that the effect mainly resulted from DMSA carried into cells by the nanoparticles. This study thus first reported the cytotoxicity of DMSA at the gene transcription level as coating molecules of FeNPs. This study provides new insight into the molecular mechanism by which the DMSA-coated nanoparticles resulted in the transcriptional changes of many CRP-coding genes in cells. This study draws attention toward the intracellular cytotoxicity of DMSA as a coating molecule of nanoparticles, which has very low toxicity as an orally administered antidote due to its extracellular distribution. PMID- 26378956 TI - Exciton-Plasmon Coupling Enhancement via Metal Oxidation. AB - In this paper, we report on the effect of metal oxidation on strong coupling interactions between silver nanostructures and a J-aggregated cyanine dye. We show that metal oxidation can sensibly affect the plexcitonic system, inducing a change in the coupling strength. In particular, we demonstrate that the presence of oxide prevents the appearance of Rabi splitting in the extinction spectra for thick spacers. In contrast, below a threshold percentage, the oxide layer results in an higher coupling strength between the plasmon and the Frenkel exciton. Contrary to common belief, a thin oxide layer seems thus to act, under certain conditions, as a coupling mediator between an emitter and a localized surface plasmon excited in a metallic nanostructure. This suggests that metal oxidation can be exploited as a means to enhance light-matter interactions in strong coupling applications. PMID- 26378957 TI - Relationship between radiocesium contamination and the contents of various elements in the web spider Nephila clavata (Nephilidae: Arachnida). AB - The accident at the Fukushima Dai-ichi nuclear power plant seriously contaminated a large area in northeast Japan with a large amount of radioactive material. Consequently, various organisms, including arthropods, in the ecosystem have been contaminated with radiocesium ((137)Cs) through the food chain. We previously showed that the web spider Nephila clavata was contaminated with (137)Cs and that the level of contamination, which varied among spider individuals, was independent of the amount of prey consumed. The present study aimed to clarify the mechanisms that could determine the level of (137)Cs contamination in N. clavata. We first demonstrated the patterns of contents of over 30 elements in N. clavata that were collected at two forest sites (PS and ES) in Fukushima and then focused on the relationships between the contents of the alkali metals Li, Na, K, and Rb and the accumulation of (137)Cs in the spiders; Cs is an alkali metal and is expected to act similarly to Li, Na, K, and Rb. We also focused on the content of the non-alkali element, Cu, which is an essential element for oxygen transport in spiders. We found that Na content correlated positively with (137)Cs accumulation at both sites, which suggested that (137)Cs accumulation in N. clavata was related with the dynamics of Na. The K-, Rb-, and Cu-(137)Cs relationships were site specific; the relationships were significant at site PS, but not significant at site ES. Factors causing the site specific relationships and the probable pathway for (137)Cs transfer from soil to plants and then to higher trophic levels are discussed in terms of the transfer processes of the alkali metals. PMID- 26378958 TI - A new comparison of marine dispersion model performances for Fukushima Dai-ichi releases in the frame of IAEA MODARIA program. AB - A detailed intercomparison of marine dispersion models applied to the releases from Fukushima Dai-ichi nuclear power plant was carried out in the frame of MODARIA program, of the IAEA. Models were compared in such a way that the reasons of the discrepancies between them can be assessed (i.e., if they are due to the hydrodynamic part, the dispersion part, and the ultimate reasons). A sequential chain of dispersion exercises was carried out with this purpose. The overall idea is to harmonize models, making them run with the same forcing in a step-by-step procedure, in such a way that the main agent in producing discrepancy between models can be found. It was found that the main reason of discrepancies between models is due to the description of the hydrodynamics. However, once this has been suppressed, some variability between model outputs remains due to intrinsic differences between models (as numerical schemes). The numerical experiments were carried out for a perfectly conservative radionuclide and for (137)Cs (including water/sediment interactions). Model outputs for this radionuclide were also compared with measurements in water and sediments. PMID- 26378959 TI - Radionuclide biological half-life values for terrestrial and aquatic wildlife. AB - The equilibrium concentration ratio is typically the parameter used to estimate organism activity concentrations within wildlife dose assessment tools. Whilst this is assumed to be fit for purpose, there are scenarios such as accidental or irregular, fluctuating, releases from licensed facilities when this might not be the case. In such circumstances, the concentration ratio approach may under- or over-estimate radiation exposure depending upon the time since the release. To carrying out assessments for such releases, a dynamic approach is needed. The simplest and most practical option is representing the uptake and turnover processes by first-order kinetics, for which organism- and element-specific biological half-life data are required. In this paper we describe the development of a freely available international database of radionuclide biological half-life values. The database includes 1907 entries for terrestrial, freshwater, riparian and marine organisms. Biological half-life values are reported for 52 elements across a range of wildlife groups (marine = 9, freshwater = 10, terrestrial = 7 and riparian = 3 groups). Potential applications and limitations of the database are discussed. PMID- 26378960 TI - Sub-supercritical liquefaction of rice stalk for the production of bio-oil: Effect of solvents. AB - The effect of solvents (water and ethanol) on liquefaction characteristics of rice stalk (RS) was investigated in an autoclave. The highest conversion and liquid yield in water and ethanol were 84.95 wt%, 72.62 wt% and 78.93wt%, 63.84 wt%, respectively. FTIR and GC-MS of the bio-oils obtained from subcritical water (SubH2O, 300 degrees C) and supercritical ethanol (scEtOH, 300 degrees C) indicated that the behavior of RS liquefaction depended on solvents used. The major components of bio-oil produced in SubH2O were ketones and phenols, while esters and phenols dominated in scEtOH. ICP-OES analysis showed that the concentrations of potassium (K) and sodium (Na) in the bio-oil obtained from scEtOH were 14-15 times higher than that obtained from SubH2O. Ethanol gave rise to an improvement in the bio-oil properties including water content, density, acidity and HHV. It was concluded that the bio-oil from RS can be effectively upgraded in scEtOH. PMID- 26378961 TI - Mathematical modeling of enzyme production using Trichoderma harzianum P49P11 and sugarcane bagasse as carbon source. AB - A mathematical model to describe the kinetics of enzyme production by the filamentous fungus Trichoderma harzianum P49P11 was developed using a low cost substrate as main carbon source (pretreated sugarcane bagasse). The model describes the cell growth, variation of substrate concentration and production of three kinds of enzymes (cellulases, beta-glucosidase and xylanase) in different sugarcane bagasse concentrations (5; 10; 20; 30; 40 gL(-1)). The 10 gL(-1) concentration was used to validate the model and the other to parameter estimation. The model for enzyme production has terms implicitly representing induction and repression. Substrate variation was represented by a simple degradation rate. The models seem to represent well the kinetics with a good fit for the majority of the assays. Validation results indicate that the models are adequate to represent the kinetics for a biotechnological process. PMID- 26378962 TI - Biomass to hydrogen-rich syngas via catalytic steam gasification of bio oil/biochar slurry. AB - The catalytic steam gasification of bio-oil/biochar slurry (bioslurry) for hydrogen-rich syngas production was investigated in a fixed-bed reactor using LaXFeO3 (X=Ce, Mg, K) perovskite-type catalysts. The effects of elemental substitution in LaFeO3, temperature, water to carbon molar ratio (WCMR) and bioslurry weight hourly space velocity (WbHSV) were examined. The results showed that La0.8Ce0.2FeO3 gave the best performance among the prepared catalysts and had better catalytic activity and stability than the commercial 14 wt.% Ni/Al2O3. The deactivation caused by carbon deposition and sintering was significantly depressed in the case of La0.8Ce0.2FeO3 catalyst. Both higher temperature and lower WbHSV contributed to more H2 yield. The optimal WCMR was found to be 2, and excessive introducing of steam reduced hydrogen yield. The La0.8Ce0.2FeO3 catalyst gave a maximum H2 yield of 82.01% with carbon conversion of 65.57% under the optimum operating conditions (temperature=800 degrees C, WCMR=2 and WbHSV=15.36h(-1)). PMID- 26378964 TI - Antibacterial Surgical Silk Sutures Using a High-Performance Slow-Release Carrier Coating System. AB - Sutures are a vital part for surgical operation, and suture-associated surgical site infections are an important issue of postoperative care. Antibacterial sutures have been proved to reduce challenging complications caused by bacterial infections. In recent decades, triclosan-free sutures have been on their way to commercialization. Alternative antibacterial substances are becoming relevant to processing surgical suture materials. Most of the antibacterial substances are loaded directly on sutures by dipping or coating methods. The aim of this study was to optimize novel antibacterial braided silk sutures based on levofloxacin hydrochloride and poly(epsilon-caprolactone) by two different processing sequences, to achieve suture materials with slow-release antibacterial efficacy and ideal physical and handling properties. Silk strands were processed into sutures on a circular braiding machine, and antibacterial treatment was introduced alternatively before or after braiding by two-dipping-two-rolling method (M1 group and M2 group). The antibacterial activity and durability against Staphylococcus aureus and Escherichia coli were tested. Drug release profiles were measured in phosphate buffer with different pH values, and release kinetics model was built to analyze the sustained drug release mechanism between the interface of biomaterials and the in vitro aqueous environment. Knot-pull tensile strength, thread-to-thread friction, and bending stiffness were determined to evaluate physical and handling properties of sutures. All coated sutures showed continuous antibacterial efficacy and slow drug release features for more than 5 days. Besides, treated sutures fulfilled U.S. Pharmacopoeia required knot-pull tensile strength. The thread-to-thread friction and bending stiffness for the M1 group changed slightly when compared with those of uncoated ones. However, physical and handling characteristics of the M2 group tend to approach those of monofilament ones. The novel suture showed acceptable in vitro cytotoxicity according to ISO 10993-5. Generally speaking, all coated sutures show potential in acting as antibacterial suture materials, and M1 group is proved to have a higher prospect for clinical applications. PMID- 26378963 TI - Randomized Trial of Communication Facilitators to Reduce Family Distress and Intensity of End-of-Life Care. AB - RATIONALE: Communication with family of critically ill patients is often poor and associated with family distress. OBJECTIVES: To determine if an intensive care unit (ICU) communication facilitator reduces family distress and intensity of end of-life care. METHODS: We conducted a randomized trial at two hospitals. Eligible patients had a predicted mortality greater than or equal to 30% and a surrogate decision maker. Facilitators supported communication between clinicians and families, adapted communication to family needs, and mediated conflict. MEASUREMENTS AND MAIN RESULTS: Outcomes included depression, anxiety, and post traumatic stress disorder (PTSD) among family 3 and 6 months after ICU and resource use. We identified 488 eligible patients and randomized 168. Of 352 eligible family members, 268 participated (76%). Family follow-up at 3 and 6 months ranged from 42 to 47%. The intervention was associated with decreased depressive symptoms at 6 months (P = 0.017), but there were no significant differences in psychological symptoms at 3 months or anxiety or PTSD at 6 months. The intervention was not associated with ICU mortality (25% control vs. 21% intervention; P = 0.615) but decreased ICU costs among all patients (per patient: $75,850 control, $51,060 intervention; P = 0.042) and particularly among decedents ($98,220 control, $22,690 intervention; P = 0.028). Among decedents, the intervention reduced ICU and hospital length of stay (28.5 vs. 7.7 d and 31.8 vs. 8.0 d, respectively; P < 0.001). CONCLUSIONS: Communication facilitators may be associated with decreased family depressive symptoms at 6 months, but we found no significant difference at 3 months or in anxiety or PTSD. The intervention reduced costs and length of stay, especially among decedents. This is the first study to find a reduction in intensity of end-of-life care with similar or improved family distress. Clinical trial registered with www.clinicaltrials.gov (NCT 00720200). PMID- 26378965 TI - From necessity to sufficiency in memory research: when sleep helps to understand wake experiences. AB - Memory is the ability to adapt our behavior by using the stored information, previously encoded. The first investigations of the neuronal bases of the memory trace concerned its properties (location, cellular and molecular mechanisms, among others). However, to understand how this is achieved at the scale of neurons, we must provide evidence about the necessity of a neuronal subpopulation to support the memory trace, but also its sufficiency. Here, we will present past and recent studies that provide information about the neuronal nature of memories. We will show that research on sleep, when cells assembly supposedly carrying information from the past are replayed, could also provide valuable information about the memory processes at stake during wake. PMID- 26378966 TI - Phytoplankton and the Macondo oil spill: A comparison of the 2010 phytoplankton assemblage to baseline conditions on the Louisiana shelf. AB - The Macondo oil spill was likely the largest oil spill to ever occur in United States territorial waters. We report herein our findings comparing the available baseline phytoplankton data from coastal waters west of the Mississippi River, and samples collected monthly from the same sampling stations, during and after the oil spill (May-October, 2010). Our results indicate that overall, the phytoplankton abundance was 85% lower in 2010 versus the baseline, and that the species composition of the phytoplankton community moved towards diatoms and cyanobacteria and away from ciliates and phytoflagellates. The results of this study reaffirm the view that phytoplankton responses will vary by the seasonal timing of the oil spill and the specific composition of the spilled oil. The trophic impacts of the purported lower abundance of phytoplankton in 2010 coupled with the observed assemblage shift remain unknown. PMID- 26378967 TI - Individual and population intake fractions of diesel particulate matter (DPM) in bus stop microenvironments. AB - Diesel particulate matter (DPM) is associated with adverse human health effects. This study aims to investigate the relationship between DPM exposure and emissions by estimating the individual intake fraction (iFi) and population intake fraction (iFp) of DPM. Daily average concentrations of particulate matter at two bus stops during rush hours were measured, and then they were apportioned to DPM due to heavy-duty diesel bus emissions using Chemical Mass Balance Model. The DPM emissions of diesel buses for different driving conditions (idling, creeping and traveling) were estimated on the basis of field observations and published emission factors. The median iFi of DPM was 0.67 and 1.39 per million for commuters standing at the bus stop and pedestrians/cyclists passing through the bus stop during rush hours, respectively. The median iFp of DPM was 94 per million. Estimations of iFi and iFp of DPM are potentially significant for exposure assessment and risk management. PMID- 26378968 TI - Influence of feeding and earthworm density on compound bioaccumulation in earthworms Eisenia andrei. AB - Earthworm density and feeding during exposure to contaminated soil have been used inconsistently in bioaccumulation studies, which may lead to possible errors in risk assessment and modeling. Hydrophobic organic pollutants with a wide range of environmental properties (phenanthrene, pyrene, lindane, p,p'-DDT, and PCB 153) were used to study the effect of different earthworm densities in combination with the presence or absence of feeding on bioaccumulation factors (BAFs). Similar BAFs were found at various soil-to-worm ratios, with the exception of phenanthrene. We recommend using at least 15 gsoil dw per earthworm. The absence of feeding doubled the BAFs and, thus, using no food ration can be considered as "the worst case scenario". Whenever food is to be applied (i.e. to ensure the validity of the test in earthworm mass loss), we suggest feeding depending on the organic carbon content of the studied soil. PMID- 26378969 TI - Multigenerational contaminant exposures produce non-monotonic, transgenerational responses in Daphnia magna. AB - Generally, ecotoxicologists rely on short-term tests that assume populations to be static. Conversely, natural populations may be exposed to the same stressors for many generations, which can alter tolerance to the same (or other) stressors. The objective of this study was to improve our understanding of how multigenerational stressors alter life history traits and stressor tolerance. After continuously exposing Daphnia magna to cadmium for 120 days, we assessed life history traits and conducted a challenge at higher temperature and cadmium concentrations. Predictably, individuals exposed to cadmium showed an overall decrease in reproductive output compared to controls. Interestingly, control D. magna were the most cadmium tolerant to novel cadmium, followed by those exposed to high cadmium. Our data suggest that long-term exposure to cadmium alter tolerance traits in a non-monotonic way. Because we observed effects after one generation removal from cadmium, transgenerational effects may be possible as a result of multigenerational exposure. PMID- 26378970 TI - On sample size estimation and re-estimation adjusting for variability in confirmatory trials. AB - Sample size estimation (SSE) is an important issue in the planning of clinical studies. While larger studies are likely to have sufficient power, it may be unethical to expose more patients than necessary to answer a scientific question. Budget considerations may also cause one to limit the study to an adequate size to answer the question at hand. Typically at the planning stage, a statistically based justification for sample size is provided. An effective sample size is usually planned under a pre-specified type I error rate, a desired power under a particular alternative and variability associated with the observations recorded. The nuisance parameter such as the variance is unknown in practice. Thus, information from a preliminary pilot study is often used to estimate the variance. However, calculating the sample size based on the estimated nuisance parameter may not be stable. Sample size re-estimation (SSR) at the interim analysis may provide an opportunity to re-evaluate the uncertainties using accrued data and continue the trial with an updated sample size. This article evaluates a proposed SSR method based on controlling the variability of nuisance parameter. A numerical study is used to assess the performance of proposed method with respect to the control of type I error. The proposed method and concepts could be extended to SSR approaches with respect to other criteria, such as maintaining effect size, achieving conditional power, and reaching a desired reproducibility probability. PMID- 26378971 TI - The interplay of parental support, parental pressure and test anxiety--Gender differences in adolescents. AB - This study examined gender-specific relationships between adolescents' perceptions of school-related support/pressure from their parents and test anxiety. A sample of German students (N = 845; Mage = 15.32; SD = .49) completed questionnaires that measured their perceived parental support/pressure (for mother and father separately) as well as the four main components of test anxiety (worry, interference, lack of confidence, and emotionality). Gender-specific relations were identified using multigroup structural equation modeling: For girls, perceived maternal pressure was positively associated with emotionality and interference; for boys, perceived father pressure and father support were positively associated with interference and worry, respectively. For both genders, perceived mother pressure and support were related to lack of confidence. Our findings suggest that adolescents' perceptions of maternal attitudes are associated with students' self-confidence irrespective of the child's gender, whereas the remaining facets of test anxiety follow same-sex trajectories between perceived parental attitudes and adolescents' test anxiety. PMID- 26378972 TI - Serologic and Molecular Prevalence of Rickettsia helvetica and Anaplasma phagocytophilum in Wild Cervids and Domestic Mammals in the Central Parts of Sweden. AB - Both Rickettsia helvetica and Anaplasma phagocytophilum are common in Ixodes ricinus ticks in Sweden. Knowledge is limited regarding different animal species' competence to act as reservoirs for these organism. For this reason, blood samples were collected from wild cervids (roe deer, moose) and domestic mammals (horse, cat, dog) in central Sweden, and sera were tested using immunofluorescence assay to detect antibodies against spotted fever rickettsiae using Rickettsia helvetica as antigen. Sera with a titer >=1:64 were considered as positive, and 23.1% (104/450) of the animals scored positive. The prevalence of seropositivity was 21.5% (23/107) in roe deer, 23.3% (21/90) in moose, 36.5% (23/63) in horses, 22.1% (19/90) in cats, and 17.0% (17/100) in dogs. PCR analysis of 113 spleen samples from moose and sheep from the corresponding areas were all negative for rickettsial DNA. In roe deer, 85% (91/107) also tested seropositive for A. phagocytophilum with a titer cutoff of 1:128. The findings indicate that the surveyed animal species are commonly exposed to rickettsiae and roe deer also to A. phagocytophilum. PMID- 26378973 TI - Development of an Orientia tsutsugamushi Lc-1 Murine Intraperitoneal Challenge Model for Scrub Typhus: Determination of Murine Lethal Dose (MuLD50), Tissue Bacterial Loads, and Clinical Outcomes. AB - Currently, no vaccine has been developed to protect humans from naturally acquired heterologous Orientia tsutsugamushi infections. To enhance the validity of vaccine candidates, we are developing a murine chigger challenge model with the O. tsutsugamushi Lc-1-infected Leptotrombidium chiangraiensis Line-1. To this end, an intraperitoneal (i.p.) murine challenge model using an O. tsutsugamushi Lc-1 isolate was developed for eventual validation of the chigger challenge model. We have determined that the murine lethal dose that kills 50% of the challenged mice (MuLD50) of a liver/spleen homogenate developed from O. tsutsugamushi Lc-1-infected ICR Swiss mice to be 10(-6.9). Employing different inoculum doses of this homogenate, the bacterial load using quantitative real time PCR (qPCR) was determined to range from 60 to 1.6 * 10(5) genome equivalent copies (GEC)/MUL of liver and 33.4 to 2.2 * 10(5) GEC/MUL of spleen tissue. The clinical outcomes relative to homogenate dose levels followed a dose-dependent pattern. The successful development and characterization of the O. tsutsugamushi Lc-1 i.p. challenge model will assist in the development and validation of a mouse chigger challenge scrub typhus model. PMID- 26378974 TI - Salmonella Isolates in the Introduced Asian House Gecko (Hemidactylus frenatus) with Emphasis on Salmonella Weltevreden, in Two Regions in Costa Rica. AB - The Asian house gecko Hemidactylus frenatus has been widely introduced in Costa Rica and tends to establish in human settlements. Some studies in other invaded countries have suggested that this gecko plays a significant role in the epidemiology of salmonellosis and it is of value to public health. To our knowledge, no studies have examined Salmonella from this species in Costa Rica. Therefore, we collected 115 geckos from houses in two Costa Rican regions. We examined gut contents for Salmonella through microbiological analysis. Presumptive Salmonella spp. were sent to a reference laboratory for serotyping and antimicrobial susceptibility testing. Molecular typing was also conducted with the main Salmonella isolates of zoonotic relevance in Costa Rica. H. frenatus was found in 95% of the houses surveyed. Salmonella was isolated in 4.3% of the samples, and four zoonotic serovars were detected. None of the isolates were resistant to the antibiotics most frequently used for salmonellosis treatment in Costa Rica. All Salmonella isolates from the lower gut of H. frenatus are associated with human salmonellosis. Pulsotypes from Salmonella enterica serotype Weltevreden were identical to the only clone previously reported from human samples in Costa Rica. Molecular typing of Salmonella Weltevreden suggested that H. frenatus harbors a serovar of public health importance in Costa Rica. Results demonstrated that H. frenatus plays a role in the epidemiology of human salmonellosis in two regions of Costa Rica. However, more detailed epidemiological studies are needed to understand better the role of the Asian house gecko with human salmonellosis, especially caused by Salmonella Weltevreden, and to quantify its risk in Costa Rica accurately. PMID- 26378975 TI - ABTS as an Electron Shuttle to Enhance the Oxidation Kinetics of Substituted Phenols by Aqueous Permanganate. AB - In this study, it was, interestingly, found that 2,2'-azino-bis(3 ethylbenzothiazoline)-6-sulfonate (ABTS), a widely used electron shuttle, could greatly accelerate the oxidation of substituted phenols by potassium permanganate (Mn(VII)) in aqueous solutions at pH 5-9. This was attributed to the fact that these substituted phenols could be readily oxidized by the stable radical cation (ABTS(*+)), which was quickly produced from the oxidation of ABTS by Mn(VII). The reaction of Mn(VII) with ABTS exhibited second-order kinetics, with stoichiometries of ~5:1 at pH 5-6 and ~3:1 at pH 7-9, and the rate constants varied negligibly from pH 5 to 9 (k = (9.44 +/- 0.21) * 10(4) M(-1) s(-1)). Comparatively, the reaction of ABTS(*+) with phenol showed biphasic kinetics. The second-order rate constants for the reactions of ABTS(*+) with substituted phenols obtained in the initial phase were strongly affected by pH, and they were several orders of magnitude higher than those for the reactions of Mn(VII) with substituted phenols at each pH. Good Hammett-type correlations were found for the reactions of ABTS(*+) with undissociated (log(k) = 2.82-4.31sigma) and dissociated phenols (log(k) = 7.29-5.90sigma). The stoichiometries of (2.2 +/- 0.06):1 (ABTS(*+) in excess) and (1.38 +/- 0.18):1 (phenol in excess) were achieved in the reaction of ABTS(*+) with phenol, but they exhibited no pH dependency. PMID- 26378976 TI - Hyaluronic acid-serum hydrogels rapidly restore metabolism of encapsulated stem cells and promote engraftment. AB - BACKGROUND: Cell death due to anoikis, necrosis and cell egress from transplantation sites limits functional benefits of cellular cardiomyoplasty. Cell dissociation and suspension, which are a pre-requisite for most cell transplantation studies, lead to depression of cellular metabolism and anoikis, which contribute to low engraftment. OBJECTIVE: We tissue engineered scaffolds with the goal of rapidly restoring metabolism, promoting viability, proliferation and engraftment of encapsulated stem cells. METHODS: The carboxyl groups of HA were functionalized with N-hydroxysuccinimide (NHS) to yield HA succinimidyl succinate (HA-NHS) groups that react with free amine groups to form amide bonds. HA-NHS was cross-linked by serum to generate HA:Serum (HA:Ser) hydrogels. Physical properties of HA:Ser hydrogels were measured. Effect of encapsulating cardiosphere-derived cells (CDCs) in HA:Ser hydrogels on viability, proliferation, glucose uptake and metabolism was assessed in vitro. In vivo acute intra-myocardial cell retention of (18)FDG-labeled CDCs encapsulated in HA:Ser hydrogels was quantified. Effect of CDC encapsulation in HA:Ser hydrogels on in vivo metabolism and engraftment at 7 days was assessed by serial, dual isotope SPECT-CT and bioluminescence imaging of CDCs expressing the Na-iodide symporter and firefly luciferase genes respectively. Effect of HA:Ser hydrogels +/- CDCs on cardiac function was assessed at 7 days & 28 days post-infarct. RESULTS: HA:Ser hydrogels are highly bio-adhesive, biodegradable, promote rapid cell adhesion, glucose uptake and restore bioenergetics of encapsulated cells within 1 h of encapsulation, both in vitro and in vivo. These metabolic scaffolds can be applied epicardially as a patch to beating hearts or injected intramyocardially. HA:Ser hydrogels markedly increase acute intramyocardial retention (~6 fold), promote in vivo viability, proliferation, engraftment of encapsulated stem cells and angiogenesis. CONCLUSION: HA:Ser hydrogels serve as 'synthetic stem cell niches' that rapidly restore metabolism of encapsulated stem cells, promote stem cell engraftment and angiogenesis. These first ever, tissue engineered metabolic scaffolds hold promise for clinical translation in conjunction with CDCs and possibly other stem cell types. PMID- 26378977 TI - Insights regarding the normal and abnormal formation of the atrial and ventricular septal structures. AB - Knowledge of cardiac development can provide the basis for understanding the morphogenesis of congenital cardiac malformations. Only recently, however, has the quality of information regarding cardiac embryology been sufficient to justify this approach. In this review, we show how such knowledge of development of the normal atrial and ventricular septal structures underscores the interpretation of the lesions that provide the basis for interatrial and interventricular shunting of blood. We show that current concepts of atrial septation, which frequently depend on a suggested formation of an extensive secondary septum, are simplistic. There are additional contributions beyond growth of the primary septum, but the new tissue is added to form the ventral buttress of the definitive atrial septum, rather than its cranial margin, as is usually depicted. We show that the ventricular septum possesses muscular and membranous components, with the entirety of the muscular septum produced concomitant with the so-called ballooning of the apical ventricular component. It is expansion of the atrioventricular canal that creates the inlet of the right ventricle, with no separate formation of an "inlet" septum. The proximal parts of the outflow cushions initially form a septal structure between the developing ventricular outlets, but this becomes converted into the free-standing muscular subpulmonary infundibulum as the aortic outlet is transferred to the left ventricle. These features of normal development are then shown to provide the basis for understanding of the channels that provide the means for interatrial and interventricular shunting. PMID- 26378979 TI - An analytical quality by design (aQbD) approach for a L-asparaginase activity method. AB - L-asparaginase is an effective anti-tumor agent for acute lymphoblastic leukemia. This work presents the development of an activity determination of L-ASNase preparations for pharmaceutical quality control purposes, in accordance with analytical Quality by Design principles. Critical method attributes, the absorbance at 450 nm (A450) of the Nessler product as well as its variability, were evaluated as a function of critical method variables, by using experimental designs. The design space of the enzyme activity assay was defined (Nessler method: C(KI)/C(HgI2) of 1.90-1.95, C(NaOH)/C(HgI2) of 17.0-18.0, C(HgI2final) of 20-40 mM and time of 10-40 min; enzyme activity conditions: temperature range of 36.6-37.4 degrees C, pH range of the KH2PO4 buffer from 7.1 to 7.7, KH2PO4 buffer concentration: 0.18-0.22 M and L-Asn concentration of 18-22 mM), leading to a final enzyme activity assay method. A control strategy was ultimately implemented using system suitability tests. PMID- 26378980 TI - Lactic Acidosis in Sepsis: It's Not All Anaerobic: Implications for Diagnosis and Management. AB - Increased blood lactate concentration (hyperlactatemia) and lactic acidosis (hyperlactatemia and serum pH < 7.35) are common in patients with severe sepsis or septic shock and are associated with significant morbidity and mortality. In some patients, most of the lactate that is produced in shock states is due to inadequate oxygen delivery resulting in tissue hypoxia and causing anaerobic glycolysis. However, lactate formation during sepsis is not entirely related to tissue hypoxia or reversible by increasing oxygen delivery. In this review, we initially outline the metabolism of lactate and etiology of lactic acidosis; we then address the pathophysiology of lactic acidosis in sepsis. We discuss the clinical implications of serum lactate measurement in diagnosis, monitoring, and prognostication in acute and intensive care settings. Finally, we explore treatment of lactic acidosis and its impact on clinical outcome. PMID- 26378981 TI - Aspertetranones A-D, Putative Meroterpenoids from the Marine Algal-Associated Fungus Aspergillus sp. ZL0-1b14. AB - Aspertetranones A-D (1-4), four new highly oxygenated putative rearranged triketide-sesquiterpenoid meroterpenes, were isolated from the marine algal associated fungus Aspergillus sp. ZL0-1b14. On the basis of a comprehensive spectroscopic analysis, the planar structures of aspertetranones were determined to possess an unusual skeleton in the terpenoid part. The relative and absolute configurations of the aspertetranones were assigned on the basis of NOESY analysis, X-ray crystallography, and circular dichroism spectroscopy. Compounds 1 4 were evaluated for anti-inflammatory activity in LPS-stimulated RAW264.7 macrophages. Aspertetranone D exhibited an inhibitory effect against IL-6 production with 69% inhibition at 40 MUM. PMID- 26378982 TI - Future Directions: How Virtual Reality Can Further Improve the Assessment and Treatment of Eating Disorders and Obesity. AB - Transdisciplinary efforts for further elucidating the etiology of eating and weight disorders and improving the effectiveness of the available evidence-based interventions are imperative at this time. Recent studies indicate that computer generated graphic environments-virtual reality (VR)-can integrate and extend existing treatments for eating and weight disorders (EWDs). Future possibilities for VR to improve actual approaches include its use for altering in real time the experience of the body (embodiment) and as a cue exposure tool for reducing food craving. PMID- 26378983 TI - Vision Impairment and Chronic Health Conditions: Implications for Services. PMID- 26378985 TI - Hepatic Disposition of Gemfibrozil and Its Major Metabolite Gemfibrozil 1-O-beta Glucuronide. AB - Gemfibrozil (GEM), which decreases serum triglycerides and low density lipoprotein, perpetrates drug-drug interactions (DDIs) with several drugs. These DDIs are primarily attributed to the inhibition of drug transporters and metabolic enzymes, particularly cytochrome P450 (CYP) 2C8 by the major circulating metabolite gemfibrozil 1-O-beta-glucuronide (GG). Here, we characterized the transporter-mediated hepatic disposition of GEM and GG using sandwich-cultured human hepatocytes (SCHH) and transporter-transfect systems. Significant active uptake was noted in SCHH for the metabolite. GG, but not GEM, showed substrate affinity to organic anion transporting polypeptide (OATP) 1B1, 1B3, and 2B1. In SCHH, glucuronidation was characterized affinity constants (Km) of 7.9 and 61.4 MUM, and biliary excretion of GG was observed. Furthermore, GG showed active basolateral efflux from preloaded SCHH and ATP-dependent uptake into membrane vesicles overexpressing multidrug resistance-associated protein (MRP) 2, MRP3, and MRP4. A mathematical model was developed to estimate hepatic uptake and efflux kinetics of GEM and GG based on SCHH studies. Collectively, the hepatic transporters play a key role in the disposition and thus determine the local concentrations of GEM and more so for GG, which is the predominant inhibitory species against CYP2C8 and OATP1B1. PMID- 26378984 TI - Weak tradeoff between xylem safety and xylem-specific hydraulic efficiency across the world's woody plant species. AB - The evolution of lignified xylem allowed for the efficient transport of water under tension, but also exposed the vascular network to the risk of gas emboli and the spread of gas between xylem conduits, thus impeding sap transport to the leaves. A well-known hypothesis proposes that the safety of xylem (its ability to resist embolism formation and spread) should trade off against xylem efficiency (its capacity to transport water). We tested this safety-efficiency hypothesis in branch xylem across 335 angiosperm and 89 gymnosperm species. Safety was considered at three levels: the xylem water potentials where 12%, 50% and 88% of maximal conductivity are lost. Although correlations between safety and efficiency were weak (r(2) < 0.086), no species had high efficiency and high safety, supporting the idea for a safety-efficiency tradeoff. However, many species had low efficiency and low safety. Species with low efficiency and low safety were weakly associated (r(2) < 0.02 in most cases) with higher wood density, lower leaf- to sapwood-area and shorter stature. There appears to be no persuasive explanation for the considerable number of species with both low efficiency and low safety. These species represent a real challenge for understanding the evolution of xylem. PMID- 26378986 TI - Drugs That Bind to alpha-Synuclein: Neuroprotective or Neurotoxic? AB - The misfolding of alpha-synuclein is a critical event in the death of dopaminergic neurons and the progression of Parkinson's disease. Drugs that bind to alpha-synuclein and form a loop structure between the N- and C-terminus tend to be neuroprotective, whereas others that cause a more compact structure tend to be neurotoxic. The binding of several natural products and other drugs that are involved in dopamine metabolism were investigated by nanopore analysis and isothermal titration calorimetry. The antinausea drugs, cinnarizine and metoclopramide, do not bind to alpha-synuclein, whereas amphetamine and the herbicides, paraquat and rotenone, bind tightly and cause alpha-synuclein to adopt a more compact conformation. The recreational drug, cocaine, binds to alpha synuclein, whereas heroin and methadone do not. Metformin, which is prescribed for diabetes and is neuroprotective, binds well without causing alpha-synuclein to adopt a more compact conformation. Methylphenidate (ritalin) binds to sites in both the N- and C-terminus and causes alpha-synuclein to adopt a loop conformation. In contrast, amphetamine only binds to the N-terminus. Except for cinnarizine and metoclopramide, there is a good correlation between the mode of binding to alpha-synuclein and whether a drug is neuroprotective or neurotoxic. PMID- 26378987 TI - Determination of ecliptasaponin A in rat plasma and tissues by liquid chromatography-tandem mass spectrometry. AB - A sensitive, rapid and specific high-performance liquid chromatography tandem mass spectrometry method (HPLC-MS/MS) was developed to determine ecliptasaponin A in rat plasma and tissues after oral administration. Ginsenoside Rg1 was used as the internal standard (IS). The plasma and tissues samples were prepared by liquid-liquid extraction with ethyl acetate and separated on an Eclipse Plus C18 column (2.1 mm * 150 mm, 5 um) at a flow rate of 0.4 mL/min using acetonitrile and water (containing 0.05% acetic acid) as the mobile phase. The tandem mass detection was carried out with eletrospray ionization in negative mode. Quantification was performed by using multiple reaction monitoring (MRM), which monitored the fragmentation of m/z 633.4->587.2 for ecliptasaponin A and m/z 859.4->637.4 for the IS. The calibration curves obtained were linear in different matrices, and the lower limit of quantification (LLOQ) achieved was 0.5 ng/mL both for rat plasma and tissues. The intra- and inter-day precisions were below 15%. This method was successfully applied to pharmacokinetic study of ecliptasaponin A in rat plasma and tissues after oral administration. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26378988 TI - Performance analysis of optical coherence tomography in the context of a thickness estimation task. AB - Thickness estimation is a common task in optical coherence tomography (OCT). This study discusses and quantifies the intensity noise of three commonly used broadband sources, such as a supercontinuum source, a superluminescent diode (SLD), and a swept source. The performance of the three optical sources was evaluated for a thickness estimation task using both the fast Fourier transform (FFT) and maximum-likelihood (ML) estimators. We find that the source intensity noise has less impact on a thickness estimation task compared to the width of the axial point-spread function (PSF) and the trigger jittering noise of a swept source. Findings further show that the FFT estimator yields biased estimates, which can be as large as 10% of the thickness under test in the worst case. The ML estimator is by construction asymptotically unbiased and displays a 10* improvement in precision for both the supercontinuum and SLD sources. The ML estimator also shows the ability to estimate thickness that is at least 10* thinner compared to the FFT estimator. Finally, findings show that a supercontinuum source combined with the ML estimator enables unbiased nanometer class thickness estimation with nanometer-scale precision. PMID- 26378989 TI - Tunable Polarity in a III-V Nanowire by Droplet Wetting and Surface Energy Engineering. AB - Controllable axial switching of polarity in GaAs nanowires with minimal tapering and perfect twin-free ZB structure based on the fundamental understanding of nanowire growth and kinking mechanism is presented. The polarity of the bottom segment is confirmed to be (111)A by atomically resolved scanning transmission electron microscopy. PMID- 26378990 TI - Programmed Death Ligand 1 Promotes Early-Life Chlamydia Respiratory Infection Induced Severe Allergic Airway Disease. AB - Chlamydia infections are frequent causes of respiratory illness, particularly pneumonia in infants, and are linked to permanent reductions in lung function and the induction of asthma. However, the immune responses that protect against early life infection and the mechanisms that lead to chronic lung disease are incompletely understood. In the current study, we investigated the role of programmed death (PD)-1 and its ligands PD-L1 and PD-L2 in promoting early-life Chlamydia respiratory infection, and infection-induced airway hyperresponsiveness (AHR) and severe allergic airway disease in later life. Infection increased PD-1 and PD-L1, but not PD-L2, mRNA expression in the lung. Flow cytometric analysis of whole lung homogenates identified monocytes, dendritic cells, CD4(+), and CD8(+) T cells as major sources of PD-1 and PD-L1. Inhibition of PD-1 and PD-L1, but not PD-L2, during infection ablated infection-induced AHR in later life. Given that PD-L1 was the most highly up-regulated and its targeting prevented infection-induced AHR, subsequent analyses focused on this ligand. Inhibition of PD-L1 had no effect on Chlamydia load but suppressed infection-induced pulmonary inflammation. Infection decreased the levels of the IL-13 decoy receptor in the lung, which were restored to baseline levels by inhibition of PD-L1. Finally, inhibition of PD-L1 during infection prevented subsequent infection-induced severe allergic airways disease in later life by decreasing IL-13 levels, Gob-5 expression, mucus production, and AHR. Thus, early-life Chlamydia respiratory infection-induced PD-L1 promotes severe inflammation during infection, permanent reductions in lung function, and the development of more severe allergic airway disease in later life. PMID- 26378992 TI - The effect of bioturbation by Lumbriculus variegatus on transport and distribution of lead in a freshwater microcosm. AB - The present study investigated the effect of bioturbation by the oligochaete worm Lumbriculus variegatus on the transport and environmental distribution of lead (Pb). Experiments used L. variegatus at densities of 0 ind./m(2), 2093 ind./m(2), and 8372 ind./m(2), in freshwater microcosms with Pb-spiked sediment. At the end of the 14-d experiment, Pb levels in the water column, tissues of L. variegatus, and sediment were determined, and bioturbation was quantified using luminophores. The bioturbation by L. variegatus increased Pb transport from the sediment to the water column. However, it did not significantly affect Pb bioaccumulation by L. variegatus or Pb levels in the sediment. The biodiffusion coefficient (Db) was positively related to worm density, but did not differ between Pb-spiked sediment and uncontaminated sediment. The latter finding suggests that Pb at the 100 MUg/g concentration used in the present study did not affect L. variegatus bioturbation. The present study shows that bioturbation can enhance Pb transfer across the sediment-water interface and thus enhance Pb availability to organisms in the water column. PMID- 26378993 TI - Recent Advancements in Nanogenerators for Energy Harvesting. AB - Nanomaterial-based generators are a highly promising power supply for micro/nanoscale devices, capable of directly harvesting energy from ambient sources without the need for batteries. These generators have been designed within four main types: piezoelectric, triboelectric, thermoelectric, and electret effects, and consist of ZnO-based, silicon-based, ferroelectric-material based, polymer-based, and graphene-based examples. The representative achievements, current challenges, and future prospects of these nanogenerators are discussed. PMID- 26378991 TI - Congenital Central Hypoventilation Syndrome: Neurocognition Already Reduced in Preschool-Aged Children. AB - BACKGROUND: Congenital Central Hypoventilation Syndrome (CCHS) is a rare neurocristopathy characterized by severe hypoventilation and autonomic dysregulation, with typical presentation in the neonatal period, and deficient cognitive skills in school-aged patients. We hypothesized that younger (preschool) children with CCHS would also show neurocognitive delay and that CCHS related physiologic factors would impact neurocognitive test results. METHODS: We studied developmental (Bayley) test results collected during routine clinical care in 31 children (mean age 25.0 +/- 8.5 months; range, 6-40 months) with PHOX2B mutation-confirmed CCHS by comparing them with the normative reference mean from the Bayley standardization sample; we also examined associations between Bayley scores and CCHS disease-related factors. RESULTS: Preschool patients with CCHS fell significantly below the normative mean of 100 on Bayley indices of mental (mean, 83.35 +/- 24.75) and motor (mean, 73.33 +/- 20.48) development (P < .001 for both). Significantly lower Bayley mental and motor scores were associated with severe breath-holding spells, prolonged sinus pauses, and need for 24 h/d artificial ventilation. Lower Bayley motor scores were also associated with seizures. Bayley scores differed among children with the three most common polyalanine repeat expansion mutation genotypes (mental, P = .001; motor, P = .006), being essentially normal in children with the 20/25 genotype but significantly lower in the other genotype groups (P < .05). CONCLUSIONS: These results confirm neurodevelopmental impairment of CCHS preschoolers, with severity related to physiologic compromise and PHOX2B genotype. These findings suggest that adverse effects begin early in the disease process, supporting the need for neurodevelopmental monitoring and intervention from early infancy. PMID- 26378994 TI - Importance of education in bronchial asthma treatment - gender differences. AB - INTRODUCTION: Despite significant progress in understanding mechanisms and effective treatment there are still therapeutic failures in patients treated for bronchial asthma. Education is vital in the therapeutic process. It improves the control of the disease at the individual level by influencing the adherence and compliance. MATERIAL AND METHODS: The study included 100 patients suffering from bronchial asthma and treated according to GINA 2002 guidelines in Allergy Clinic. Asthma control test (ACT), analysis of patients' medical documentation and a self constructed questionnaire concerning health promotion and education were used in the study. Aim of this work was to assess differences in the influence of education on results of bronchial asthma control between sexes. RESULTS: Average duration of asthma was similar in women and men (13.0 +/- 11.16 vs.12.7 +/- 9.74 years). Weaker asthma control was found in women (ACT 17.7 vs. 20.4), as well as lower FEV1 values (80-50% of predicted value in 60.3% of women vs. 43.25 of men). In women an analysis of correlation concerning patients' knowledge and conducted health education with asthma control revealed a statistically significant positive correlation of knowledge acquired from the allergologist with asthma control, information about proceeding in acute attack, whereas negative correlation with asthma control with knowledge passed on by family doctor was found. Among the male respondents positive correlations of knowledge with asthma control within the scope of knowledge from allergologist and information concerning proceeding in asthmatic attack were found, while negative correlation with information coming from family doctor was revealed. CONCLUSIONS: Health education in patients with asthma should be conducted by a specialist in allergic diseases and well-prepared healthcare professionals. PMID- 26378995 TI - Thrombocytopenia as a marker of outcome in patients with acute exacerbation of chronic obstructive pulmonary disease. AB - INTRODUCTION: Thrombocytopenia (TP) is associated with poor outcome in patients who are critically ill with pneumonia, burns, and H1N1 influenza. To our knowledge, no similar study in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) has been conducted to date. The aim of this study was to determine the impact of platelet count on the outcome of patients with AECOPD. MATERIAL AND METHODS: Patients admitted to our teaching hospital for AECOPD were divided into two cohorts, those with and without TP. The outcome of all patients was followed. RESULTS: Of the 200 patients with AECOPD, 55 (27.5%) had TP. Of these, 14 (25.5%) died in the hospital, whereas of the 145 non-TP patents, 11 (7.5%) died (p-value = 0.001). There was a significantly higher transfer rate to the ICU and mechanical ventilation in TP patients. The mean platelet count was significantly lower in patients who died than those who were discharged (161,672 vs. 203,005 cell/MUL; p-value = 0.017). There was negative correlation between duration of hospitalization and platelet count. CONCLUSION: TP was associated with poor outcome in AECOPD. TP could be considered as a marker for the assessment of inflammation and prognosis in AECOPD patients based on its cost-effective features. PMID- 26378996 TI - Evaluation of the quality of life in subjects with a history of severe anaphylactic reaction to the Hymenoptera venom. AB - INTRODUCTION: Sensitization to the Hymenoptera venom is one of the main causes of anaphylaxis in Poland. Venom immunotherapy is the only effective treatment in such cases. Comprehensive patient care includes also education. The aim of our study was to assess the state of knowledge and to evaluate the quality of life and the anxiety level in patients allergic to the Hymenoptera venom after anaphylactic reaction. MATERIAL AND METHODS: The survey was carried out in the period of the insects flight in 61 adult subjects (35 wasp and 26 bee allergic), using a validated Vespid Allergy Quality of Life Questionnaire (VQLQ), Hospital Anxiety and Depression Scale, and subjective assessment of anxiety level. The majority of respondents received venom immunotherapy. RESULTS: Sensitized to the wasp venom had significantly impaired quality of life (VQLQ score) as compared to the bee venom allergic (p = 0.014). The intensity of anxiety decreased with the duration of immunotherapy (p = 0.01). The majority of subjects knew how to recognize and treat anaphylaxis, but only 8% employed an identification card and about 50% implemented rules of the pre-exposition prophylaxis. CONCLUSIONS: History of a severe anaphylaxis to the Hymenoptera venom affected the quality of life. Venom immunotherapy reduced anxiety. We hope that presented surveys and their results might be useful in qualifying for immunotherapy in clinically uncertain cases. PMID- 26378997 TI - Asthma prevalence and risk factors analysis in Tricity university students' group. AB - INTRODUCTION: Asthma is the most prevalent chronic disease in a young and middle age population worldwide. It is also one of the main reasons for the lost working days and lost days at school. Several epidemiological surveys have evidenced an increase in the prevalence of asthma in Poland. This trend is further evident in urban areas such as Tricity (Gdansk, Sopot, Gdynia). The aim of the study was to assess the prevalence of the disease as well as the risk factors affecting the university student population. MATERIAL AND METHODS: Two surveys were distributed electronically to students of the four major universities in Tricity. The first survey contained nine questions concerning asthma diagnoses and symptoms. The second survey, which evaluated the occurrence of identified risk factors, was sent to students who answered the first survey. Asthmatics also received an Asthma Control Test (ACT). The results were analyzed using the Statistica 10 software. Study group consisted of 1380 students: 1031 (75%) women and 349 (25%) men; the average age was 22.2. RESULTS: Asthma was diagnosed in 138 students (9.6%), additionally 76 students (5.5%) reported asthmatic symptoms; however, these students had no previous diagnoses. Asthma tended to occur more frequently in students living in poorly maintained houses (19%) (p = 0.06), in contrast to those living in a normal environment (10%). According to their ACTs, 81% of diagnosed patients reported that their asthma was well-controlled. CONCLUSIONS: Asthma is becoming an important issue for Tricity students. Educational activities aimed at raising university students' awareness regarding asthma treatment and control should be implemented. PMID- 26378978 TI - Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. AB - BACKGROUND: The effects of empagliflozin, an inhibitor of sodium-glucose cotransporter 2, in addition to standard care, on cardiovascular morbidity and mortality in patients with type 2 diabetes at high cardiovascular risk are not known. METHODS: We randomly assigned patients to receive 10 mg or 25 mg of empagliflozin or placebo once daily. The primary composite outcome was death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, as analyzed in the pooled empagliflozin group versus the placebo group. The key secondary composite outcome was the primary outcome plus hospitalization for unstable angina. RESULTS: A total of 7020 patients were treated (median observation time, 3.1 years). The primary outcome occurred in 490 of 4687 patients (10.5%) in the pooled empagliflozin group and in 282 of 2333 patients (12.1%) in the placebo group (hazard ratio in the empagliflozin group, 0.86; 95.02% confidence interval, 0.74 to 0.99; P=0.04 for superiority). There were no significant between-group differences in the rates of myocardial infarction or stroke, but in the empagliflozin group there were significantly lower rates of death from cardiovascular causes (3.7%, vs. 5.9% in the placebo group; 38% relative risk reduction), hospitalization for heart failure (2.7% and 4.1%, respectively; 35% relative risk reduction), and death from any cause (5.7% and 8.3%, respectively; 32% relative risk reduction). There was no significant between-group difference in the key secondary outcome (P=0.08 for superiority). Among patients receiving empagliflozin, there was an increased rate of genital infection but no increase in other adverse events. CONCLUSIONS: Patients with type 2 diabetes at high risk for cardiovascular events who received empagliflozin, as compared with placebo, had a lower rate of the primary composite cardiovascular outcome and of death from any cause when the study drug was added to standard care. (Funded by Boehringer Ingelheim and Eli Lilly; EMPA REG OUTCOME ClinicalTrials.gov number, NCT01131676.). PMID- 26378999 TI - Interstitial lung disease associated with docetaxel in a patient treated for breast cancer - a case report. AB - Docetaxel is a semisynthetic cytostatic drug that belongs to the family of taxoids. Docetaxel inhibits normal interphase and mitotic cellular function, causing cell death. Docetaxel is indicated for the treatment of breast, lung and prostate cancers, head and neck cancer and gastric adenocarcinoma. Interstitial pneumonitis is an uncommon side effect of docetaxel. We report a case of docetaxel induced interstitial lung disease (ILD) in a patient with breast cancer. PMID- 26378998 TI - Usage and usability of one dry powder inhaler compared to other inhalers at therapy start: an open, non-interventional observational study in Poland and Germany. AB - INTRODUCTION: Inhalation is the preferred route of drug administration for patients with asthma or COPD. It is generally predicted that there is a high error rate in inhaler usage, especially at the therapy start. The primary objective of this study was the validation of a questionnaire that can be used for assessing a successful inhalation technique, patient satisfaction as well as the compliance in daily practice.The secondary objective was to examine the "real life" usage of one inhalation device in comparison with other devices at the start of the therapy. MATERIAL AND METHODS: This open, multi centre and non interventional study was designed to examine usage and usability of dry powder inhaler Easyhaler(r) (EH) (Orion Pharma, Finland) and other inhalers assessed by the physicians as well as by the patients. Inclusion criteria for patients were a physician-diagnosis of COPD or asthma or children with asthmatic disease, therapy start with an inhalation device and no or only few experiences with inhaler usage (inhaler usage for not more than 3 months). Each physician enrolled an equal number of patients in each group. RESULTS: 263 adult/adolescent patients with asthma and 115 with COPD as well as 164 children with asthmatic disease were enrolled. 49.4% of the adult/adolescent patients with asthma used an EH and 50.6% other inhalers. In the case of COPD, 47.8% were treated with an EH and 52.2% used other inhalation devices. Finally, 50.6% of the children with asthmatic disease used an EH and 49.4% were treated with other inhalers. Inhaler usage, patient satisfaction, compliance and patients assessments of usability were better when the patients used an EH. Inconvenient features were mainly documented for other inhalers. The analysis of Cronbachs alpha clearly showed the consistency of the received data from all patients. In addition, there was a large association between the assessment of the inhaler usage and the general assessment of the used inhaler in all patient groups. CONCLUSION: The results of this study show that investigators found EH easy to teach, the patients found it easy to use and their satisfaction with the device was high in comparison to other inhalation devices. Thus EH can be matched to many patients already at the therapy start. In addition, the high consistency of the received data and large association of the assessment of the inhaler usage and the general assessment of the inhaler indicate that the used questionnaires were appropriate tools to examine usage and usability of inhaler devices in adult patients and children. PMID- 26379000 TI - Chronic pneumonia due to Klebsiella oxytoca mimicking pulmonary tuberculosis. AB - Klebsiella species infrequently cause acute community acquired pneumonia (CAP). The chronic form of the disease caused by K. pneumoniae (Friedlander's bacillus) was occasionally seen in the pre-antibiotic era. K. oxytoca is a singularly uncommon cause of CAP. The chronic form of the disease caused by K. oxytoca has been documented only once before. A 50-year-old immunocompetent male smoker presented with haemoptysis for 12 months. Imaging demonstrated a cavitary lesion in the right upper lobe with emphysematous changes. Sputum stains and cultures for Mycobacterium tuberculosis were negative. However, three sputum samples for aerobic culture as well as bronchial aspirate cultured pure growth of K. oxytoca. A diagnosis of chronic pneumonia due to K. oxytoca was established and with appropriate therapy, the patient was largely asymptomatic. The remarkable clinical and radiological similarity to pulmonary tuberculosis can result in patients with chronic Klebsiella pneumonia erroneously receiving anti-tuberculous therapy. PMID- 26379001 TI - Middle lobe syndrome: an extraordinary presentation of endobronchial tuberculosis. AB - Tuberculous infection of the tracheobronchial tree, termed as endobronchial tuberculosis (EBTB), is more common in young adults and females. This clinical entity is poorly understood and the diagnosis is frequently delayed as sputum smears are often negative for acid fast bacilli and the chest radiograph can be normal, resulting in diagnostic confusion. Bronchoscopy continues to play a key role in its diagnosis. Though atelectasis is not uncommon in these patients, EBTB presenting as a middle lobe syndrome (MLS) has rarely been documented. MLS refers to chronic or recurrent collapse of the right middle lobe and has a myriad of causes. The pathogenesis of this entity too is not fully established. We report this exceptional clinical manifestation in a 19-year-old male, who presented for evaluation of respiratory symptoms for 6 months along with constitutional complaints. Imaging suggested the presence of MLS and bronchoscopy established the diagnosis of endobronchial tuberculosis. GeneXpert evaluation of bronchial aspirate detected Mycobacterium tuberculosis. Histopathology confirmed the presence of granulomatous lesions. Subsequently, the cultures of bronchial aspirate and post-bronchoscopy sputum grew M. tuberculosis. Appropriate therapy with anti-tuberculosis drugs resulted in a remarkable symptomatic and radiological improvement. EBTB presenting as a MLS is a distinct rarity. PMID- 26379002 TI - "Luck's always to blame": silent wounds of a penetrating gunshot trauma sustained 20 years ago. AB - Gunshot tracheal injuries represent life-threatening events and usually necessitate emergent surgical intervention. We report a case of an exceptional finding of a patient with retained ballistic fragments in the soft tissues of the thorax, proximal to the right subclavian artery and the trachea, carrying silently his wounds for two decades without any medical or surgical intervention. The bullet pellet on the upper part of the trachea seen accidentally in the chest computed tomography, was also found during bronchoscopy. In short "luck's always to blame". PMID- 26379003 TI - Problems of patients with cystic fibrosis during transition to adulthood. AB - The proper care of cystic fibrosis patients extends over their lifetime. More than half of the children with the disease die before adulthood. An important element in the patient's care is a time of transition from a paediatric to the care of an internist and the patient's acceptance of this necessity. Transition from paediatric care to an internist should be adequately prepared. It is not only a question of transfer of medical records, but also careful preparation of patients for such transition. The patients expect not only continuity of care but also the introduction to the management with the disease. The creation of a base for specialist hospital treatment for exacerbation of the disease at the adulthood is an important element in the care of these patients. The problem has been solved in the children group, but is still waiting for solution in adults with cystic fibrosis. It has been proven that care in the centres carried out by a specialized team ensures longer life and better quality of life of these patients. The paper is an overview of these two important elements of care of adults with cystic fibrosis. PMID- 26379004 TI - The etiology of lower respiratory tract infections in people with diabetes. AB - Patients with diabetes mellitus (DM) are likely to develop many types of infections, which affect the transport of glucose into tissues. Diabetes increases the susceptibility to different kinds of respiratory infections, is often identified as an independent risk factor for developing lower respiratory tract infections. Pulmonary infections caused by Mycobacterium tuberculosis, Staphylococcus aureus, gram-negative bacteria and fungi may occur with an increased frequency, whereas infections due to Streptococcus pneumonia or influenza virus may be associated with increased morbidity and mortality. During lung infection, there are changes in the local and ciliary epithelial lining. Increased susceptibility to pneumococcal infection by people with diabetes is the result of reduced defense capability of antibodies to protein antigens. The relationship between diabetes and pulmonary tuberculosis is well known, and the incidence of tuberculosis in diabetic individuals is 4-5 times greater than among the non-diabetic population. It is thought that malfunction of monocytes in patients with diabetes may contribute to the increased susceptibility to tuberculosis and/or a worse prognosis. Hospitalization of patients with diabetes due to influenza virus or flu-like infections is up to 6 times more likely to occur compared to healthy individuals, also diabetic patients are more likely to be hospitalized due to infection complications. Immunization with influenza and anti-pneumococcal vaccines is recommended to reduce hospitalizations, deaths, and medical expenses. Diabetes, especially the uncontrolled one, predisposes to fungal infection, the most common candidiasis and mucormycosis. PMID- 26379005 TI - Cooperation between Polish and French Pneumonologists. PMID- 26379006 TI - Surgical Techniques for the Correction of Postrhinoplasty Depressed Scars on the Nasal Tip. AB - IMPORTANCE: Augmentation rhinoplasty is common in the Asian population and the lack of suitable autologous material for augmentation has led to the use of alloplastic materials. Many of these patients develop complications, including a depressed dimple-like scar of the nasal tip. Causes of such dimpling include the use of large implants, infection, extrusion, and surgeon incompetence. OBJECTIVE: To describe the various techniques that can be used to correct dimpling of the nasal tip. DESIGN, SETTING, AND PARTICIPANTS: Data were retrospectively reviewed from 28 patients who had undergone surgical procedures from January 1, 2013, through July 31, 2014, in a rhinoplasty clinic in Seoul, Korea, for the correction of a contracted nose with nasal scars secondary to previous rhinoplasties. Data analysis was conducted from August 1, 2014, through February 16, 2015. INTERVENTIONS: Before surgery, a complete rhinological examination was conducted, digital photographs were taken, and an assessment was made regarding the severity of the dimpling, the condition of the nasal skin, and the underlying supporting structures. Based on these factors, the appropriate type of procedure was planned. MAIN OUTCOMES AND MEASURES: Patient satisfaction with change after surgery was assessed using a 3-point Likert scale (3 indicates satisfied; 2, fairly satisfied; and 1, dissatisfied). Outcomes were also reviewed by 2 surgeon peers who gave an outcome score ranging from 1 to 10 (1 indicates a poor cosmetic outcome; 10, the best possible outcome). RESULTS: The nasal contour and tip symmetry were restored to aesthetic standards with these relatively simple techniques. Eleven patients (39.2%) were treated with unilobed flap, 4 (14.2%) with a bilobed flap, 3 (10.7%) with Z-plasty, 9 (32.1%) with soft-tissue interposition, and 1 (3.5%) with a transposition flap. Twenty-four of the 28 patients (85.7%) were satisfied with their outcomes and 4 (14.3%) patients were dissatisfied and were given a revision procedure, following which they were satisfied with their outcomes. The follow-up period ranged between 6 to 32 months (mean, 12.3 months). The mean surgeon-reviewed outcome score for soft-tissue interposition procedure was 8.0 of 10; for the unilobed flap, 8.0 of 10; for the bilobed flap, 7.5 of 10; for the transposition flap, 8.0 of 10; and for Z-plasty, 7.8 of 10. CONCLUSIONS AND RELEVANCE: These techniques are reproducible and the choice of the technique depends on the shape, size, and location of the scar; skin condition; patient expectations; and the surgeon's experience and comfort level with the procedure. LEVEL OF EVIDENCE: 4. PMID- 26379008 TI - Untargeted Identification of Organo-Bromine Compounds in Lake Sediments by Ultrahigh-Resolution Mass Spectrometry with the Data-Independent Precursor Isolation and Characteristic Fragment Method. AB - While previous studies have found that unknown natural and synthetic organo bromine compounds (NSOBCs) contributed more than 99% of the total organic bromine (Br) in the environment, there was no efficient method for untargeted screening to identify NSOBCs in environmental matrixes. A novel untargeted method for identifying NSOBCs, based on ultrahigh-resolution mass spectrometry (UHRMS) with the Q Exactive instrument was developed. This method included a data-independent precursor isolation and characteristic fragment (DIPIC-Frag) procedure to identify NSOBCs. A total of 180 successive 5-m/z-wide windows were used to isolate precursor ions. This resulted in a sufficient dynamic range and specificity to identify peaks of Br fragment ions for analysis. A total of 2520 peaks of NSOBC compounds containing Br were observed in sediments from Lake Michigan, United States. A new chemometric strategy which combined chromatographic profiles, isotopic peaks, precursor isolation window information, and intensities was used to identify precursor ions and chemical formulas for detecting NSOBCs. Precursor ions for 2163 of the 2520 NSOBCs peaks (86%) were identified, and chemical formulas for 2071 NSOBCs peaks (82%) were determined. After exclusion of isotopic peaks, 1593 unique NSOBCs were identified and chemical formulas derived for each. Most of the compounds identified had not been reported previously and had intensities which were 100- to 1000-fold greater than the congeners of polybrominated diphenyl ethers (PBDEs). In extracts of sediments, these compounds exhibited variations in intensities (<10(3) to ~10(8)), m/z values (170.9438-997.5217), retention times on a C18 column (1.0 29.3 min), and the number of Br atoms (1-8). Generally, compounds with greater m/z values had longer retention times and greater numbers of Br atoms. Three compounds were used in a proof-of-concept experiment to demonstrate that structures of some of the screened NSOBCs could be further predicted by combining searching of database libraries and high-resolution MS(2) spectra. PMID- 26379009 TI - Decreasing geographic bias in Conservation Biology. PMID- 26379007 TI - Fetal growth and subsequent maternal risk of thyroid cancer. AB - Thyroid cancer has peak incidence among women of reproductive age, and growth factors, which have procarcinogenic properties, may play an important etiologic role. However, the association between fetal growth rate during a woman's pregnancy and her subsequent risk of thyroid cancer has not been previously examined. We conducted a national cohort study of 1,837,634 mothers who had a total of 3,588,497 live-births in Sweden in 1973-2008, followed up for thyroid cancer incidence through 2009. There were 2,202 mothers subsequently diagnosed with thyroid cancer in 36.8 million person-years of follow-up. After adjusting for maternal age, height, weight, smoking, and sociodemographic factors, high fetal growth (birth weight standardized for gestational age and sex) was associated with a subsequent increased risk of thyroid cancer in the mother (incidence rate ratio [IRR] per additional 1 standard deviation, 1.05; 95% CI, 1.01-1.09; p = 0.02). Each 1,000 g increase in the infant's birth weight was associated with a 13% increase in the mother's subsequent risk of thyroid cancer (IRR, 1.13; 95% CI, 1.05-1.22; p = 0.001). These findings appeared to involve both papillary and follicular subtypes, and did not vary significantly by the mother's height, weight or smoking status. In this large national cohort study, high fetal growth during a woman's pregnancy was independently associated with a subsequent increased risk of her developing thyroid cancer. If confirmed, these findings suggest an important role of maternal growth factors in the development of thyroid cancer, and potentially may help facilitate the identification of high risk subgroups of women. PMID- 26379011 TI - PandemrixTM and narcolepsy: A critical appraisal of the observational studies. AB - A link between PandemrixTM (AS03-adjuvanted H1N1 pandemic influenza vaccine, GSK Vaccines, Belgium) and narcolepsy was first suspected in 2010 in Sweden and Finland following a number of reports in children and adolescents. Initial scepticism about the reported association faded as additional countries reported similar findings, leading several regulatory authorities to restrict the use of PandemrixTM. The authors acknowledge that currently available data suggest an increased risk of narcolepsy following vaccination with PandemrixTM; however, from an epidemiologist's perspective, significant methodological limitations of the studies have not been fully addressed and raise questions about the reported risk estimates. We review the most important biases and confounders that potentially occurred in 12 European studies of the observed association between PandemrixTM and narcolepsy, and call for further analyses and debate. PMID- 26379012 TI - Searching for harmony in transition-metal signaling. PMID- 26379013 TI - Host-directed drug therapy for tuberculosis. PMID- 26379014 TI - Voices of chemical biology. PMID- 26379021 TI - Metals: Calprotectin and iron match up. PMID- 26379022 TI - Metabolism: Jump-starting CoA biosynthesis. PMID- 26379023 TI - Small-molecule inhibitors: bULKing up mTOR inhibition. PMID- 26379024 TI - Metalloproteins: Simple structure, complex function. PMID- 26379025 TI - Corrigendum: Structural basis of enzymatic benzene ring reduction. PMID- 26379026 TI - Erratum: Pharmacological targeting of the Wdr5-MLL interaction in C/EBPalpha N terminal leukemia. PMID- 26379027 TI - Corrigendum: Structural basis for selective binding of m(6)A RNA by the YTHDC1 YTH domain. PMID- 26379028 TI - Higher Decorin Levels in Bone Marrow Plasma Are Associated with Superior Treatment Response to Novel Agent-Based Induction in Patients with Newly Diagnosed Myeloma - A Retrospective Study. AB - The growth of myeloma cells depends on bone marrow (BM) stroma consisting of stromal cells, secreted cytokines and the extracellular matrix (ECM). Decorin, a small leucine-rich proteoglycan in the ECM, is a signaling ligand and native anti tumor agent. However, the role of decorin in patients with myeloma is not clear. We evaluated the correlation between the decorin levels measured by enzyme-linked immunosorbent assay in BM plasma from 121 patients with newly diagnosed myeloma based on their clinical features and treatment response. The median decorin levels in the patients and the normal control group were 12.31 ng/mL [standard deviation (SD), 7.50 ng/mL; range, 2.45 to 44.46 ng/mL] and 10.31 ng/mL (SD, 2.42 ng/mL; range, 4.85-15.14 ng/mL), respectively (P < 0.001). Using 15.15 ng/mL as a cut-off, 46 patients (38%) exhibited higher decorin levels (H-DCN), whereas the other patients exhibited normal to lower decorin levels (NL-DCN). Except for the median age, which was significantly younger in the H-DCN than in the NL-DCN group (60.6 +/- 14.0 vs. 65.8 +/- 12.2 years, respectively; P = 0.034), there were no differences between the two groups. However, in 79 patients who had received novel agent-based induction, the overall response rate was significantly better in the H-DCN than in the NL-DCN (97 vs. 63%, respectively; P < 0.001), as was the depth of responses (P = 0.008), which were not observed in those who had received chemotherapeutic agents alone. Progression-free survival (PFS) was significantly longer in H-DCN than NL-DCN (not reached vs. 19.5 mo, respectively; P = 0.0003). Multivariate analyses indicated that H-DCN, as a significantly independent factor, was associated with better treatment response (odds ratio, 20.014; 95% CI, 2.187-183.150; P = 0.008) and longer PFS (hazard ratio, 0.135; 95% CI, 0.051 0.361; P < 0.001). These findings disclose the potential role of decorin in myeloma and provide a basis for further study on possible synergistic anti myeloma effects between decorin and the novel agents that target BM stroma. PMID- 26379029 TI - Cytoprotective Effect of Ferritin H in Renal Ischemia Reperfusion Injury. AB - Oxidative stress is a major contributor to kidney injury following ischemia reperfusion. Ferritin, a highly conserved iron-binding protein, is a key protein in the maintenance of cellular iron homeostasis and protection from oxidative stress. Ferritin mitigates oxidant stress by sequestering iron and preventing its participation in reactions that generate reactive oxygen species. Ferritin is composed of two subunit types, ferritin H and ferritin L. Using an in vivo model that enables conditional tissue-specific doxycycline-inducible expression of ferritin H in the mouse kidney, we tested the hypothesis that an increased level of H-rich ferritin is renoprotective in ischemic acute renal failure. Prior to induction of ischemia, doxycycline increased ferritin H in the kidneys of the transgenic mice nearly 6.5-fold. Following reperfusion for 24 hours, induction of neutrophil gelatinous-associated lipocalin (NGAL, a urine marker of renal dysfunction) was reduced in the ferritin H overexpressers compared to controls. Histopathologic examination following ischemia reperfusion revealed that ferritin H overexpression increased intact nuclei in renal tubules, reduced the frequency of tubular profiles with luminal cast materials, and reduced activated caspase-3 in the kidney. In addition, generation of 4-hydroxy 2-nonenal protein adducts, a measurement of oxidant stress, was decreased in ischemia-reperfused kidneys of ferritin H overexpressers. These studies demonstrate that ferritin H can inhibit apoptotic cell death, enhance tubular epithelial viability, and preserve renal function by limiting oxidative stress following ischemia reperfusion injury. PMID- 26379030 TI - The Unrecognized Burden of Influenza in Young Kenyan Children, 2008-2012. AB - Influenza-associated disease burden among children in tropical sub-Saharan Africa is not well established, particularly outside of the 2009 pandemic period. We estimated the burden of influenza in children aged 0-4 years through population based surveillance for influenza-like illness (ILI) and acute lower respiratory tract illness (ALRI). Household members meeting ILI or ALRI case definitions were referred to health facilities for evaluation and collection of nasopharyngeal and oropharyngeal swabs for influenza testing by real-time reverse transcription polymerase chain reaction. Estimates were adjusted for health-seeking behavior and those with ILI and ALRI who were not tested. During 2008-2012, there were 9,652 person-years of surveillance among children aged 0-4 years. The average adjusted rate of influenza-associated hospitalization was 4.3 (95% CI 3.0-6.0) per 1,000 person-years in children aged 0-4 years. Hospitalization rates were highest in the 0-5 month and 6-23 month age groups, at 7.6 (95% CI 3.2-18.2) and 8.4 (95% CI 5.4-13.0) per 1,000 person-years, respectively. The average adjusted rate of influenza-associated medically attended (inpatient or outpatient) ALRI in children aged 0-4 years was 17.4 (95% CI 14.2-19.7) per 1,000 person-years. Few children who had severe laboratory-confirmed influenza were clinically diagnosed with influenza by the treating clinician in the inpatient (0/33, 0%) or outpatient (1/109, 0.9%) settings. Influenza-associated hospitalization rates from 2008-2012 were 5-10 times higher than contemporaneous U.S. estimates. Many children with danger signs were not hospitalized; thus, influenza-associated severe disease rates in Kenyan children are likely higher than hospital-based estimates suggest. PMID- 26379031 TI - Inappropriate Use of Antibiotics and Its Associated Factors among Urban and Rural Communities of Bahir Dar City Administration, Northwest Ethiopia. AB - BACKGROUND: Inappropriate use of antibiotics in the community plays a role in the emergence and spread of bacteria resistant to antibiotics which threatens human health significantly. The present study was designed to determine inappropriate use of antibiotics and its associated factors among urban and rural communities of Bahir Dar city administration. METHODS: A comparative cross sectional study design was conducted in urban and rural kebeles of Bahir Dar city administration from February 1 to March 28, 2014. A total of 1082 participants included in the study using a systematic random sampling technique. Data was collected using pre tested and structured questionnaire. Data was coded and entered into SPSSS version 16 for statistical analysis. Bivariate and multivariate logistic regression model were used to identify factors associated with inappropriate use of antibiotics. RESULTS: Inappropriate use of antibiotics was 30.9% without significant difference between urban (33.1%) and rural (29.2%) communities. From the inappropriate antibiotic use practice, self-medication was 18.0% and the remaining (12.9%) was for family member medication. Respiratory tract symptoms (74.6%), diarrhea (74.4%), and physical injury/wound (64.3%) were the three main reasons that the communities had used antibiotics inappropriately. Factors associated with inappropriate use of antibiotics were low educational status, younger age, unsatisfaction with the health care services, engagement with a job, and low knowledge on the use of antibiotic preparations of human to animals. CONCLUSIONS: Inappropriate use of antibiotic exists in the study area with no significant difference between urban and rural communities. The study indicated an insight on what factors that intervention should be made to reduce inappropriate use of antibiotics in the community. Interventions that consider age groups, educational status, common health problems and their jobs together with improvement of health care services should be areas of focus to reduce inappropriate use of antibiotics. PMID- 26379033 TI - Dearomative Indole Bisfunctionalization via a Diastereoselective Palladium Catalyzed Arylcyanation. AB - The first Pd-catalyzed dearomative indole bisfunctionalization via a diastereoselective arylcyanation is reported. This method facilitates the formation of diverse indoline scaffolds bearing congested stereocenters with high levels of diastereoselectivity. This also represents the first example of a cyanation mechanism involving a 2 degrees benzylic Pd(II) intermediate. PMID- 26379032 TI - CD44 Binding to Hyaluronic Acid Is Redox Regulated by a Labile Disulfide Bond in the Hyaluronic Acid Binding Site. AB - CD44 is the primary leukocyte cell surface receptor for hyaluronic acid (HA), a component of the extracellular matrix. Enzymatic post translational cleavage of labile disulfide bonds is a mechanism by which proteins are structurally regulated by imparting an allosteric change and altering activity. We have identified one such disulfide bond in CD44 formed by Cys77 and Cys97 that stabilises the HA binding groove. This bond is labile on the surface of leukocytes treated with chemical and enzymatic reducing agents. Analysis of CD44 crystal structures reveal the disulfide bond to be solvent accessible and in the LH hook configuration characteristic of labile disulfide bonds. Kinetic trapping and binding experiments on CD44-Fc chimeric proteins show the bond is preferentially reduced over the other disulfide bonds in CD44 and reduction inhibits the CD44-HA interaction. Furthermore cells transfected with CD44 no longer adhere to HA coated surfaces after pre-treatment with reducing agents. The implications of CD44 redox regulation are discussed in the context of immune function, disease and therapeutic strategies. PMID- 26379035 TI - Environmental and Behavioural Determinants of Leptospirosis Transmission: A Systematic Review. AB - BACKGROUND: Leptospirosis is one of the most widespread zoonotic diseases, which is of global medical and veterinary importance, and also a re-emerging infectious disease. The main tracks of transmission are known; however, the relative importance of each of the components and the respective environmental risk factors are unclear. We aimed to assess and specify quantitative evidence of environmental risks of leptospirosis transmission. METHODS/FINDINGS: A database of pre-selected studies, with publication dates from 1970 until 2008, was provided by an expert group. The database has been updated until 2015 using a text mining algorithm. Study selection was based on stringent quality criteria. A descriptive data analysis was performed to calculate the medians of the log transformed odds ratios. From a selection of 2723 unique publications containing information on leptospirosis, 428 papers dealing with risk factors were identified. Of these, 53 fulfilled the quality criteria, allowing us to identify trends in different geo-climatic regions. Water associated exposures were, with few exceptions, associated with an increased leptospirosis risk. In resource poor countries, floods and rainfall were of particular importance, whereas recreational water activities were more relevant in developed countries. Rodents were associated with increased leptospirosis risk, but the variation among studies was high, which might be partly explained by differences in exposure definition. Livestock contact was commonly associated with increased risk; however, several studies found no association. The median odds ratios associated with dog and cat contacts were close to unity. Sanitation and behavioural risk factors were almost always strongly associated with leptospirosis, although their impact was rarely investigated in Europe or North America. CONCLUSION: This review confirms the complex environmental transmission pathways of leptospirosis, as previously established. Although, floods appeared to be among the most important drivers on islands and in Asia, the consistent pattern observed for exposure to rodents and behavioural and sanitation related risk factors indicate potential areas for intervention. PMID- 26379036 TI - Screening Physical Activity in Family Practice: Validity of the Spanish Version of a Brief Physical Activity Questionnaire. AB - OBJECTIVES: The use of brief screening tools to identify inactive patients is essential to improve the efficiency of primary care-based physical activity (PA) programs. However, the current employment of short PA questionnaires within the Spanish primary care pathway is unclear. This study evaluated the validity of the Spanish version of a Brief Physical Activity Assessment Tool (SBPAAT). METHODS: A validation study was carried out within the EVIDENT project. A convenience sample of patients (n = 1,184; age 58.9+/-13.7 years; 60.5% female) completed the SBPAAT and the 7-day Physical Activity Recall (7DPAR) and, in addition, wore an accelerometer (ActiGraph GT3X) for seven consecutive days. Validity was evaluated by measuring agreement, Kappa correlation coefficients, sensitivity and specificity in achieving current PA recommendations with the 7DPAR. Pearson correlation coefficients with the number of daily minutes engaged in moderate and vigorous intensity PA according to the accelerometer were also assessed. Comparison with accelerometer counts, daily minutes engaged in sedentary, light, moderate, and vigorous intensity PA, total daily kilocalories, and total PA and leisure time expenditure (METs-hour-week) between the sufficiently and insufficiently active groups identified by SBPAAT were reported. RESULTS: The SBPAAT identified 41.3% sufficiently active (n = 489) and 58.7% insufficiently active (n = 695) patients; it showed moderate validity (k = 0.454, 95% CI: 0.402 0.505) and a specificity and sensitivity of 74.3% and 74.6%, respectively. Validity was fair for identifying daily minutes engaged in moderate (r = 0.215, 95% CI:0.156 to 0.272) and vigorous PA (r = 0.282, 95% CI:0.165 to 0.391). Insufficiently active patients according to the SBPAAT significantly reported fewer counts/minute (-22%), fewer minutes/day of moderate (-11.38) and vigorous PA (-2.69), spent fewer total kilocalories/day (-753), and reported a lower energy cost (METs-hour-week) of physical activities globally (-26.82) and during leisure time (-19.62). CONCLUSIONS: The SBPAAT is a valid tool to identify Spanish-speaking patients who are insufficiently active to achieve health benefits. PMID- 26379039 TI - An Evolutionary Approach for Identifying Driver Mutations in Colorectal Cancer. AB - The traditional view of cancer as a genetic disease that can successfully be treated with drugs targeting mutant onco-proteins has motivated whole-genome sequencing efforts in many human cancer types. However, only a subset of mutations found within the genomic landscape of cancer is likely to provide a fitness advantage to the cell. Distinguishing such "driver" mutations from innocuous "passenger" events is critical for prioritizing the validation of candidate mutations in disease-relevant models. We design a novel statistical index, called the Hitchhiking Index, which reflects the probability that any observed candidate gene is a passenger alteration, given the frequency of alterations in a cross-sectional cancer sample set, and apply it to a mutational data set in colorectal cancer. Our methodology is based upon a population dynamics model of mutation accumulation and selection in colorectal tissue prior to cancer initiation as well as during tumorigenesis. This methodology can be used to aid in the prioritization of candidate mutations for functional validation and contributes to the process of drug discovery. PMID- 26379038 TI - Synthesis and Characterization of Cobalt(III), Nickel(II) and Copper(II) Mononuclear Complexes with the Ligand 1,3-bis[(2-aminoethyl)amino]-2-propanol and Their Catalase-Like Activity. AB - In this work, we present the synthesis and characterization of two new mononuclear complexes with the ligand 1,3-bis[(2-aminoethyl)amino]-2-propanol (HL), [Co(L)(H2O)](ClO4)2 (1), [Ni(HL)](ClO4)2 (2), as well as the known complex [Cu(HL)](ClO4)2 (3) for comparison. Their abilities to catalyze the dismutation of H2O2 and the oxidation of cyclohexane were investigated. The complexes were characterized by X-ray diffraction, elemental analysis, electronic and infrared spectroscopy, cyclic voltammetry, electrospray ionization mass spectrometry (ESI MS) and conductivity measurements. The X-ray structures showed that the nickel (2) and copper (3) complexes are tetracoordinated, with the metal ion bound to the nitrogen atoms of the ligand. On the other hand, the cobalt complex (1) is hexacoordinated, possessing additional bonds to the alkoxo group of the ligand and to a water molecule. Neither of the complexes was able to catalyze the oxidation of cyclohexane, but all of them exhibited catalase-like activity, following Michaelis-Menten kinetics, which suggest resemblance with the catalase natural enzymes. The catalytic activity followed the order: [Ni(HL)](ClO4)2 (2) > [Cu(HL)](ClO4)2 (3) > [Co(L)(H2O)](ClO4)2 (1). As far as we know, this is the first description of a nickel complex presenting a significant catalase-like activity. PMID- 26379037 TI - The Staphylococcus aureus ABC-Type Manganese Transporter MntABC Is Critical for Reinitiation of Bacterial Replication Following Exposure to Phagocytic Oxidative Burst. AB - Manganese plays a central role in cellular detoxification of reactive oxygen species (ROS). Therefore, manganese acquisition is considered to be important for bacterial pathogenesis by counteracting the oxidative burst of phagocytic cells during host infection. However, detailed analysis of the interplay between bacterial manganese acquisition and phagocytic cells and its impact on bacterial pathogenesis has remained elusive for Staphylococcus aureus, a major human pathogen. Here, we show that a mntC mutant, which lacks the functional manganese transporter MntABC, was more sensitive to killing by human neutrophils but not murine macrophages, unless the mntC mutant was pre-exposed to oxidative stress. Notably, the mntC mutant formed strikingly small colonies when recovered from both type of phagocytic cells. We show that this phenotype is a direct consequence of the inability of the mntC mutant to reinitiate growth after exposure to phagocytic oxidative burst. Transcript and quantitative proteomics analyses revealed that the manganese-dependent ribonucleotide reductase complex NrdEF, which is essential for DNA synthesis and repair, was highly induced in the mntC mutant under oxidative stress conditions including after phagocytosis. Since NrdEF proteins are essential for S. aureus viability we hypothesize that cells lacking MntABC might attempt to compensate for the impaired function of NrdEF by increasing their expression. Our data suggest that besides ROS detoxification, functional manganese acquisition is likely crucial for S. aureus pathogenesis by repairing oxidative damages, thereby ensuring efficient bacterial growth after phagocytic oxidative burst, which is an attribute critical for disseminating and establishing infection in the host. PMID- 26379040 TI - A phase II study of bendamustine in combination with rituximab as initial treatment for patients with indolent non-follicular non-Hodgkin lymphoma. AB - The purpose of this phase 2 study was to determine the activity and safety of six cycles of bendamustine and eight rituximab (RB) as first-line treatment of adult patients with advanced stage non-follicular indolent non-Hodgkin lymphomas (INFL). The primary end-point was the complete response rate (CRR) with expected CRR of 75%. Sixty-nine patients were enrolled; median age was 65 years (45-75), 65% were male, 93% of patients had stage IV disease. Complete and overall response rates were 48% (95% CI = 35.6-60.2) and 86% (CI = 75.0-92.8). The most common grade 3/4 adverse events were neutropenia (43%), thrombocytopenia (7%) and anemia (4%); whereas the rate of febrile neutropenia was very low (3%). At a median follow-up of 22 months (1-43 months), 2-year progression-free survival was 89% (CI = 79-95) and 2-year overall survival was 96% (CI = 87-99). RB combination is active and well tolerated in patients with advanced stage previously untreated INFL. PMID- 26379042 TI - Significance of CD163-Positive Macrophages in Proliferative Glomerulonephritis. AB - BACKGROUND: CD163, a marker of M2 macrophages, possesses anti-inflammatory properties. This study aims to investigate the clinicopathological significance of CD163-positive macrophages in proliferative glomerulonephritis. METHODS: Renal tissue samples from patients with lupus nephritis (LN, n = 22), antineutrophil cytoplasmic autoantibody (ANCA)-associated pauci-immune necrotizing glomerulonephritis (PNGN, n = 10), type 1 membranoproliferative glomerulonephritis (n = 5), minimal change disease (n = 8) and normal control kidneys (n = 3) were included in this study. The expression of CD163, CD68, CD20 and CD3 in renal tissues was detected by immunohistochemistry or immunofluorescence. The level of urinary neutrophil gelatinase-associated lipocalin (NGAL) was determined by enzyme-linked immunosorbent assay. RESULTS: CD163 was mainly expressed in active crescentic glomerulonephritis, proliferative glomerular lesions and areas of tubulointerstitial injury. Patients with LN-IV and PNGN had numerous CD163-positive cells in glomerular and acute tubulointerstitial lesions. CD163-positive cells in glomeruli positively correlated to proteinuria yet negatively correlated to estimated glomerular filtration rate. There was a positive correlation between the number of CD163 cells in acute tubulointerstitial lesions and NGAL levels, whereas a negative correlation between CD163 numbers and estimated glomerular filtration rate. The number of CD163-positive cells in crescentic glomerulonephritis was more than other groups. In LN, the number of CD163 cells in the tubulointerstitial and glomerular lesions had a positive correlation with activity index. Dual staining showed that CD163-positive cells also expressed CD68, although they did not show any staining for CD20 or CD3. CONCLUSIONS: CD163-positive macrophages were involved in the pathogenesis of proliferative glomerular lesions, active crescentic glomerulonephritis and acute tubular injury of patients with PNGN and active LN. PMID- 26379041 TI - Androgen and Progesterone Receptors Are Targets for Bisphenol A (BPA), 4-Methyl 2,4-bis-(P-Hydroxyphenyl)Pent-1-Ene--A Potent Metabolite of BPA, and 4-Tert Octylphenol: A Computational Insight. AB - Exposure to toxic industrial chemicals that have capacity to disrupt the endocrine system, also known as endocrine disrupting chemicals (EDCs), has been increasingly associated with reproductive problems in human population. Bisphenol A (BPA; 4,4'-(propane-2,2-diyl)diphenol) and 4-tert-octylphenol (OP; 4-(1,1,3,3 tetramethylbutyl)phenol) are among the most common environmental contaminants possessing endocrine disruption properties and are present in plastics, epoxy resins, detergents and other commercial products of common personal and industrial use. A metabolite of BPA, 4-Methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP) is about 1000 times more biologically active compared to BPA. Epidemiological, clinical, and experimental studies have shown association of BPA and OP with adverse effects on male and female reproductive system in human and animals. The endocrine disruption activity can occur through multiple pathways including binding to steroid receptors. Androgen receptor (AR) and progesterone receptor (PR) are critical for reproductive tract growth and function. Structural binding characterization of BPA, MBP, and OP with AR and PR using molecular docking simulation approaches revealed novel interactions of BPA with PR, and MBP and OP with AR and PR. For BPA, MBP, and OP, five AR interacting residues Leu 701, Leu-704, Asn-705, Met-742, and Phe-764 overlapped with those of native AR ligand testosterone, and four PR interacting residues Leu-715, Leu-718, Met-756, and Met-759 overlapped with those of PR co-complex ligand, norethindrone. For both the receptors the binding strength of MBP was maximum among the three compounds. Thus, these compounds have the potential to block or interfere in the binding of the endogenous native AR and PR ligands and, hence, resulting in dysfunction. The knowledge of the key interactions and the important amino-acid residues also allows better prediction of potential of xenobiotic molecules for disrupting AR- and PR-mediated pathways, thus, helping in design of less potent alternatives for commercial use. PMID- 26379043 TI - Value of Low Triiodothyronine and Subclinical Myocardial Injury for Clinical Outcomes in Chest Pain. AB - BACKGROUND: Low triiodothyronine (T3) levels and subclinical myocardial injury may be associated with adverse cardiac and cerebrovascular (CCV) events in individuals without clinically apparent coronary heart disease (CHD). The aim of this study was to determine the associations of a low T3 level and subclinical myocardial injury with the development of adverse CCV events in individuals without clinically apparent CHD. METHODS: T3 and high-sensitivity cardiac troponin T (hs-cTnT) levels were analyzed in 250 patients with chest pain free of CHD and heart failure. The primary end point was the composite of sudden cardiac death, ischemic stroke, newly developed atrial fibrillation, pericardial effusion and thrombosis. RESULTS: Throughout a mean follow-up of 15.6 months, the primary end point happened in 17 patients (6.8%). Kaplan-Meier analysis disclosed a notably higher overall occurrence rate in patients with hs-cTnT levels >=0.014 ng/mL and in patients with T3 <60 ng/dL. An exaggerated hazard was observed in patients with combined high hs-cTnT and low T3 levels. After adjustment, the hazard ratio for overall events in patients with high hs-cTnT/low T3 versus normal hs-cTnT/T3 was 11.72 (95% confidence interval, 2.83-48.57; P = 0.001). CONCLUSIONS: In patients with chest pain without clinically obvious CHD, high hs cTnT combined with low T3 was associated with adverse cardiac/CCV events and was an independent predictor of overall events even after adjustment. These data suggest the importance of systemic factors, such as low T3 syndrome, in the development of adverse cardiac/CCV events beyond advancing clinical atherosclerotic coronary disease in patients with chest pain. PMID- 26379044 TI - TMPRSS2 Isoform 1 Activates Respiratory Viruses and Is Expressed in Viral Target Cells. AB - The cellular protease TMPRSS2 cleaves and activates the influenza virus hemagglutinin (HA) and TMPRSS2 expression is essential for viral spread and pathogenesis in mice. Moreover, severe acute respiratory syndrome coronavirus (SARS-CoV) and other respiratory viruses are activated by TMPRSS2. However, previous studies on viral activation by TMPRSS2 focused on a 492 amino acids comprising form of the protein (isoform 2) while other TMPRSS2 isoforms, generated upon alternative splicing of the tmprss2 mRNA, have not been characterized. Here, we show that the mRNA encoding a TMPRSS2 isoform with an extended N-terminal cytoplasmic domain (isoform 1) is expressed in lung-derived cell lines and tissues. Moreover, we demonstrate that TMPRSS2 isoform 1 colocalizes with HA and cleaves and activates HA. Finally, we show that isoform 1 activates the SARS-CoV spike protein for cathepsin L-independent entry into target cells. Our results indicate that TMPRSS2 isoform 1 is expressed in viral target cells and might contribute to viral activation in the host. PMID- 26379045 TI - Dear Enemies Elicit Lower Androgen Responses to Territorial Challenges than Unfamiliar Intruders in a Cichlid Fish. AB - In many territorial species androgen hormones are known to increase in response to territorial intrusions as a way to adjust the expression of androgen-dependent behaviour to social challenges. The dear enemy effect has also been described in territorial species and posits that resident individuals show a more aggressive response to intrusions by strangers than by other territorial neighbours. Therefore, we hypothesized that the dear enemy effect may also modulate the androgen response to a territorial intrusion. Here we tested this hypothesis in male cichlid fish (Mozambique tilapia, Oreochromis mossambicus) using a paradigm of four repeated territorial intrusions, either by the same neighbour or by four different unfamiliar intruders. Neighbour intruders elicited lower aggression and a weaker androgen response than strangers on the first intrusion of the experiment. With repeated intrusions, the agonistic behaviour of the resident males against familiar intruders was similar to that displayed towards strangers. By the fourth intrusion the androgen response was significantly reduced and there was no longer a difference between the responses to the two types of intruders. These results suggest that the dear enemy effect modulates the androgen response to territorial intrusions and that repeated intrusions lead to a habituation of the androgen response. PMID- 26379046 TI - Stereochemical analysis of glycerophospholipids by vibrational circular dichroism. AB - The stereochemistry of glycerophospholipids (GPLs) has been of interest for its roles in the evolution of life and in their biological activity. However, because of their structural complexity, no convenient method to determine their configuration has been reported. In this work, through the first systematic application of vibrational circular dichroism (VCD) spectroscopy to various diacylated GPLs, we have revealed that their chirality can be assigned by the sign of a VCD exciton couplet generated by the interaction of two carbonyl groups. This paper also presents spectroscopic evidence for the stereochemistry of GPLs isolated from bacteria, eukaryotes, and mitochondria. PMID- 26379047 TI - Mercury- and cadmium-assisted [2 + 2] cyclodimerization of tert-butylselenium diimide. AB - The complexes [MCl2{N,N'-(t)BuNSe(MU-N(t)Bu)2SeN(t)Bu}] [M = Cd (1), Hg (2)] were obtained in high yields by the reaction of tert-butylselenium diimide Se(IV)(N(t)Bu)2 with CdCl2 or HgCl2 in tetrahydrofuran. Recrystallization of 1 and 2 from acetonitrile (MeCN) afforded yellow crystals of 1.MeCN and 2.MeCN, respectively. Isomorphic 1.MeCN and 2.MeCN contain an unprecedented dimeric selenium diimide ligand, which is N,N'-chelated to the metal through exocyclic imido groups. In addition to the complexes 1 and 2, the (77)Se NMR spectra of acetonitrile solutions of 1.MeCN and 2.MeCN indicated the presence of the dimeric (t)BuNSe(MU-N(t)Bu)2SeN(t)Bu, monomeric Se(IV)(N(t)Bu)2, and cyclic selenium imides. Density functional theory calculations at the PBE0/def2-TZVPP level of theory were used to assign the (77)Se resonances of the dimer. A comparison of Gibbs energies of formation of some metal dichloride complexes [MCl2{N,N' Se(IV)(N(t)Bu)2}] and [MCl2{N,N'-(t)BuNSe(MU-N(t)Bu)2SeN(t)Bu}] (M = Zn, Cd, Hg) indicated that the formation of complexes containing a dimeric selenium diimide ligand is favored over those containing a monomeric ligand for the group 12 metals. In the case of the group 10 metal halogenides (M = Ni, Pd, Pt), the Gibbs energies of the complexes with monomeric Se(IV)(N(t)Bu)2 ligands are close to those containing dimeric (t)BuNSe(MU-N(t)Bu)2SeN(t)Bu ligands. A plausible reaction pathway with a low activation energy involves the initial formation of [MCl2{N,N'-Se(IV)(N(t)Bu)2}] (M = Zn, Cd, Hg), which then reacts with another molecule of Se(N(t)Bu)2, leading to the final [MCl2{N,N'-(t)BuNSe(MU N(t)Bu)2SeN(t)Bu}] complex. Without the presence of group 12 metal halogenides, the [2 + 2] cyclodimerization of Se(IV)(N(t)Bu)2 is virtually thermoneutral, but the activation energy is relatively high, which accounts for the kinetic stability of (t)BuNSe(MU-N(t)Bu)2SeN(t)Bu in solution. A minor byproduct, [Cd7Cl14{N,N'-Se(II)(NH(t)Bu)2}6].4CH2Cl2, was identified by X-ray crystallography as a heptanuclear cluster with selenium(II) diamide ligands N,N' chelated to the cadmium centers. PMID- 26379049 TI - Small-molecule bioanalytical sample preparation method development starting from the BASICS. AB - AIM: To develop a robust small-molecule bioanalytical sample preparation method, systematic investigations of the bioanalytical handling conditions of analytes and IS of interest are preferred. So far, such investigations are done manually and are labor-intensive and error-prone. RESULT: An automation-assisted system has been developed to facilitate such systematic investigations. The system takes experimental design and automates the majority of the wet laboratory work. In addition, the system also automates the data extraction, recovery/loss computation, graphing and reporting. CONCLUSION: The automation-assisted system greatly reduces errors and labor involved in the systematic investigation of analytes and IS both for wet chemistry experiments and for data extraction and processing, enhances data processing efficiency and overall sample preparation method development productivity. PMID- 26379048 TI - The Prevalence and Characteristics of Fibromyalgia in the 2012 National Health Interview Survey. AB - BACKGROUND: Most knowledge of fibromyalgia comes from the clinical setting, where healthcare-seeking behavior and selection issues influence study results. The characteristics of fibromyalgia in the general population have not been studied in detail. METHODS: We developed and tested surrogate study specific criteria for fibromyalgia in rheumatology practices using variables from the US National Health Interview Survey (NHIS) and the modification (for surveys) of the 2010 American College of Rheumatology (ACR) preliminary fibromyalgia criteria. The surrogate criteria were applied to the 2012 NHIS and identified persons who satisfied criteria from symptom data. The NHIS weighted sample of 8446 persons represents 225.7 million US adults. RESULTS: Fibromyalgia was identified in 1.75% (95% CI 1.42, 2.07), or 3.94 million persons. However, 73% of identified cases self-reported a physician's diagnosis other than fibromyalgia. Identified cases had high levels of self-reported pain, non-pain symptoms, comorbidity, psychological distress, medical costs, Social Security and work disability. Caseness was associated with gender, education, ethnicity, citizenship and unhealthy behaviors. Demographics, behaviors, and comorbidity were predictive of case status. Examination of the surrogate polysymptomatic distress scale (PSD) of the 2010 ACR criteria found fibromyalgia symptoms extending through the full length of the scale. CONCLUSIONS: Persons identified with criteria-based fibromyalgia have severe symptoms, but most (73%) have not received a clinical diagnosis of fibromyalgia. The association of fibromyalgia-like symptoms over the full length of the PSD scale with physiological as well as mental stressors suggests PSD may be a universal response variable rather than one restricted to fibromyalgia. PMID- 26379050 TI - Elucidation of markers for monitoring morphine and its analogs in urine adulterated with pyridinium chlorochromate. AB - AIM: Currently, procedures that identify the drugs 'destroyed' in adulterated urine specimens are very limited. This study aimed to determine the effect of pyridinium chlorochromate (PCC) on routine opiate assays and identify reaction products formed. Results/methodology: Opiate-positive urines adulterated with PCC (20 and 100 mM) were analyzed using CEDIA(r) immunoassay and GC-MS. Urine and water samples spiked with 6-monoacetylmorphine, morphine and its glucuronides (10 ug/ml) and PCC (0.02-100 mM) were monitored with LC-MS, and the products characterized. CONCLUSION: PCC significantly decreased the abundance of morphine, codeine and IS. Adulterated water and urine samples containing 6 monoacetylmorphine, morphine and morphine-3-glucuronide yielded morphinone-3 glucuronide, 7,14-dihydroxy-6-monoacetylmorphine, 7,8-diketo-6-monoacetylmorphine and 7,8-diketo-morphine (tentative assignment). Reaction pathways may be different in the two matrices. PMID- 26379051 TI - Comparative Genotypes, Staphylococcal Cassette Chromosome mec (SCCmec) Genes and Antimicrobial Resistance amongst Staphylococcus epidermidis and Staphylococcus haemolyticus Isolates from Infections in Humans and Companion Animals. AB - This study compares the characteristics of Staphylococcus epidermidis (SE) and Staphylococcus haemolyticus (SH) isolates from epidemiologically unrelated infections in humans (Hu) (28 SE-Hu; 8 SH-Hu) and companion animals (CpA) (12 SE CpA; 13 SH-CpA). All isolates underwent antimicrobial susceptibility testing, multilocus sequence typing and DNA microarray profiling to detect antimicrobial resistance and SCCmec-associated genes. All methicillin-resistant (MR) isolates (33/40 SE, 20/21 SH) underwent dru and mecA allele typing. Isolates were predominantly assigned to sequence types (STs) within a single clonal complex (CC2, SE, 84.8%; CC1, SH, 95.2%). SCCmec IV predominated among MRSE with ST2-MRSE IVc common to both Hu (40.9%) and CpA (54.5%). Identical mecA alleles and nontypeable dru types (dts) were identified in one ST2-MRSE-IVc Hu and CpA isolate, however, all mecA alleles and 2/4 dts detected among 18 ST2-MRSE-IVc isolates were closely related, sharing >96.5% DNA sequence homology. Although only one ST-SCCmec type combination (ST1 with a non-typeable [NT] SCCmec NT9 [class C mec and ccrB4]) was common to four MRSH-Hu and one MRSH-CpA, all MRSH isolates were closely related based on similar STs, SCCmec genes (V/VT or components thereof), mecA alleles and dts. Overall, 39.6% of MR isolates harbored NT SCCmec elements, and ACME was more common amongst MRSE and CpA isolates. Multidrug resistance (MDR) was detected among 96.7% of isolates but they differed in the prevalence of specific macrolide, aminoglycoside and trimethoprim resistance genes amongst SE and SH isolates. Ciprofloxacin, rifampicin, chloramphenicol [fexA, cat-pC221], tetracycline [tet(K)], aminoglycosides [aadD, aphA3] and fusidic acid [fusB] resistance was significantly more common amongst CpA isolates. SE and SH isolates causing infections in Hu and CpA hosts belong predominantly to STs within a single lineage, harboring similar but variable SCCmec genes, mecA alleles and dts. Host and staphylococcal species-specific characteristics were identified in relation to antimicrobial resistance genes and phenotypes, SCCmec and ACME. PMID- 26379052 TI - Suppression of NF-kappaB and NF-kappaB-Regulated Gene Expression by Apigenin through IkappaBalpha and IKK Pathway in TRAMP Mice. AB - Aberrant Nuclear Factor-kappaappaB (NF-kappaB) activation due to rapid IkappaBalpha turnover and high basal IkappaBalpha kinase (IKK) activity has been frequently observed in prostate cancer. Apigenin, a naturally occurring plant flavone, exhibits anti-proliferative, anti-inflammatory and anti-carcinogenic activities by inhibiting NF-kappaB pathway, through a mechanism not fully understood. We found that apigenin feeding in microgram doses (bioavailable in humans) inhibited prostate tumorigenesis in TRAMP mice by interfering with NF kappaB signaling. Apigenin feeding to TRAMP mice (20 and 50 MUg/mouse/day, 6 days/week for 20 weeks) exhibited significant decrease in tumor volumes of the prostate and completely abolished metastasis, which correlated with inhibition of NF-kappaB activation and binding to the DNA. Apigenin intake blocked phosphorylation and degradation of IkappaBalpha by inhibiting IKK activation, which in turn led to suppression of NF-kappaB activation. The expression of NF kappaB-regulated gene products involved in proliferation (cyclin D1, and COX-2), anti-apoptosis (Bcl-2 and Bcl-xL), and angiogenesis (vascular endothelial growth factor) were also downregulated after apigenin feeding. These events correlated with the induction of apoptosis in tumor cells, as evident by increased cleaved caspase-3 labeling index in the dorsolateral prostate. Our results provide convincing evidence that apigenin inhibits IKK activation and restores the expression of IkappaBalpha, preventing it's phosphorylation in a fashion similar to that elicited by IKK and proteasomal inhibitors through suppression of NF kappaB signaling pathway. PMID- 26379053 TI - Percutaneous Coronary Intervention Utilization and Appropriateness across the United States. AB - BACKGROUND: Substantial geographic variation exists in percutaneous coronary intervention (PCI) use across the United States. It is unclear the extent to which high PCI utilization can be explained by PCI for inappropriate indications. The objective of this study was to examine the relationship between PCI rates across regional healthcare markets utilizing hospital referral regions (HRRs) and PCI appropriateness. METHODS: The number of PCI procedures in each HRR was obtained from the 2010 100% Medicare limited data set. HRRs were divided into quintiles of PCI utilization with increasing rates of utilization progressing to quintile 5. NCDR CathPCI Registry(r) data were used to evaluate patient characteristics, appropriate use criteria (AUC), and outcomes across the HRR quintiles defined by PCI utilization with the study population restricted to HRRs where >= 80% of the PCIs were performed at institutions participating in the registry. PCI appropriateness was defined using 2012 AUC by the American College of Cardiology (ACC)/American Heart Association (AHA)/The Society for Cardiovascular Angiography and Interventions (SCAI). RESULTS: Our study cohort comprised of 380,981 patients treated at 178 HRRs. Mean PCI rates per 1,000 increased from 4.6 in Quintile 1 to 10.8 in Quintile 5. The proportion of non acute PCIs was 27.7% in Quintile 1 increasing to 30.7% in Quintile 5. Significant variation (p < 0.001) existed across the quintiles in the categorization of appropriateness across HRRs of utilization with more appropriate PCI in lower utilization areas (Appropriate: Q1, 76.53%, Q2, 75.326%, Q3, 75.23%, Q4, 73.95%, Q5, 72.768%; Inappropriate: Q1 3.92%, Q2 4.23%, Q3 4.32%, Q4 4.35%, Q5 4.05%; Uncertain: Q1 8.29%, Q2 8.84%, Q3 8.08%, Q4 9.01%, Q5 8.93%; Not Mappable: Q1 11.26%, Q2 11.67%, Q3 12.37%, Q4 12.69%, Q5 14.34%). There was no difference in risk-adjusted mortality across quintiles of PCI utilization. CONCLUSIONS: Geographic regions with lower PCI rates have a higher proportion of PCIs performed for appropriate indications. Areas that perform more PCIs also appear to perform more elective PCI and many could not be mapped by the AUC. PMID- 26379054 TI - Correction: DNA Topoisomerase 1alpha Promotes Transcriptional Silencing of Transposable Elements through DNA Methylation and Histone Lysine 9 Dimethylation in Arabidopsis. PMID- 26379055 TI - Meta-Analysis of Microarray Data of Rainbow Trout Fry Gonad Differentiation Modulated by Ethynylestradiol. AB - Sex differentiation in fish is a highly labile process easily reversed by the use of exogenous hormonal treatment and has led to environmental concerns since low doses of estrogenic molecules can adversely impact fish reproduction. The goal of this study was to identify pathways altered by treatment with ethynylestradiol (EE2) in developing fish and to find new target genes to be tested further for their possible role in male-to-female sex transdifferentiation. To this end, we have successfully adapted a previously developed bioinformatics workflow to a meta-analysis of two datasets studying sex reversal following exposure to EE2 in juvenile rainbow trout. The meta-analysis consisted of retrieving the intersection of the top gene lists generated for both datasets, performed at different levels of stringency. The intersecting gene lists, enriched in true positive differentially expressed genes (DEGs), were subjected to over representation analysis (ORA) which allowed identifying several statistically significant enriched pathways altered by EE2 treatment and several new candidate pathways, such as progesterone-mediated oocyte maturation and PPAR signalling. Moreover, several relevant key genes potentially implicated in the early transdifferentiation process were selected. Altogether, the results show that EE2 has a great effect on gene expression in juvenile rainbow trout. The feminization process seems to result from the altered transcription of genes implicated in normal female gonad differentiation, resulting in expression similar to that observed in normal females (i.e. the repression of key testicular markers cyp17a1, cyp11b, tbx1), as well as from other genes (including transcription factors) that respond specifically to the EE2 treatment. The results also showed that the bioinformatics workflow can be applied to different types of microarray platforms and could be generalized to (eco)toxicogenomics studies for environmental risk assessment purposes. PMID- 26379057 TI - Electrophysiological correlates of processing subject's own name. AB - To understand the neurological mechanisms associated with the perception of subject's own name (SON) and provide a reference for assessing residual cognitive functions in patients with disorders of consciousness, event-related potentials were recorded in 16 healthy volunteers. Compared with event-related potentials elicited by tone stimuli, SON elicited larger MMN and P300. The amplitudes and latencies of MMN and P300 induced by subject's derived name (SDN) were similar to those induced by SON. Discriminating SON from SDN resulted in longer MMN and P300 latencies. These data showed that the SDN had similar quality as SON and might provide a useful reference for quantitatively evaluating disorders of consciousness. PMID- 26379056 TI - Neuroprotective Effect of Tauroursodeoxycholic Acid on N-Methyl-D-Aspartate Induced Retinal Ganglion Cell Degeneration. AB - Retinal ganglion cell degeneration underlies the pathophysiology of diseases affecting the retina and optic nerve. Several studies have previously evidenced the anti-apoptotic properties of the bile constituent, tauroursodeoxycholic acid, in diverse models of photoreceptor degeneration. The aim of this study was to investigate the effects of systemic administration of tauroursodeoxycholic acid on N-methyl-D-aspartate (NMDA)-induced damage in the rat retina using a functional and morphological approach. Tauroursodeoxycholic acid was administered intraperitoneally before and after intravitreal injection of NMDA. Three days after insult, full-field electroretinograms showed reductions in the amplitudes of the positive and negative-scotopic threshold responses, scotopic a- and b waves and oscillatory potentials. Quantitative morphological evaluation of whole mount retinas demonstrated a reduction in the density of retinal ganglion cells. Systemic administration of tauroursodeoxycholic acid attenuated the functional impairment induced by NMDA, which correlated with a higher retinal ganglion cell density. Our findings sustain the efficacy of tauroursodeoxycholic acid administration in vivo, suggesting it would be a good candidate for the pharmacological treatment of degenerative diseases coursing with retinal ganglion cell loss. PMID- 26379058 TI - MRI localization of the subthalamic nucleus in normal adults and its relation with age. AB - The subthalamic nucleus regulates motor and neurocognitive functions. Because of its small size and close proximity to other small subcortical structures, it has been a challenge to localize and visualize it using MRI. Here, we sought to define the optimal MRI scan method and visualization plane for locating the subthalamic nucleus on MRI images and to further delineate the geometric dimensions of the subthalamic nucleus and their correlation with age, laterality, and sex. Healthy volunteers received axial, sagittal, and coronal T2_3D_DRIVE CLEAR, coronal T1-WI, coronal T2FLAIR, coronal T2, and coronal SWI sequence. The coronal T2-3D-DRIVE CLEAR images were compared with the Schaltenbrand-Wahren Atlas for Stereotaxy of the Human Brain for localizing the subthalamic nucleus. The best visualization plane with the largest sectional area and the most distinct outline was obtained and region of interest was delineated manually on the basis of the contours of the bilateral subthalamic nuclei in T2-WI images. T2 3D-DRIVE CLEAR in the coronal view showed optimal visualization of the subthalamic nucleus and indicated that the subthalamic nucleus showed three morphological types: the double convex lens type (172, 64%), the ram's horn type (62, 23%), and the willow leaf type (34, 13%). There were no statistically significant differences because of laterality, sex, and age in the sectional area, and maximal long and short diameter of the subthalamic nucleus. On the basis of our results, the current study has shown that T2-3D-DRIVE CLEAR in the coronal view provides optimal visualization of the subthalamic nucleus, which shows three distinct morphological types on MRI images, and there is no statistically significant difference in the geometric dimensions of the subthalamic nucleus because of laterality, sex, and age in normal individuals. PMID- 26379059 TI - Characteristics of hyperpolarization-activated cyclic nucleotide-gated channels in dorsal root ganglion neurons at different ages and sizes. AB - In rat's sensory neurons, hyperpolarization-activated inward currents (Ih) play an essential role in mediating action potentials and contributing to neuronal excitability. Classified by the size of neurons and ages, we studied the Ih and transcription levels of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels using electrophysiology and the single-cell RT-PCR. In voltage-clamp studies, Ih and half-maximal activation voltage (V1/2) changed with age and size. An analysis of all HCN subtypes in dorsal root ganglion (DRG) neurons by single cell RT-PCR was carried out. HCN1 and HCN3 in medium-small elderly neurons had a weak expression. HCN2 in newborns and HCN4 in elderly rats also had a weak expression. The aim of this study is to examine the age-related Ih and HCN channels subunits in different ages and sizes of DRG neurons. The results would be significant in understanding the physiological and pathophysiological function of different sizes of DRG neurons in different age periods. PMID- 26379060 TI - To bet or not to bet? The coding of bets modulates brain potentials in outcome evaluations. AB - Decisions made on the basis of risk often require rapid evaluation of feedback before follow-up actions and feedback-related negativity in brain potential is sensitive to the poor outcome. The current study investigated the effects of feedback from one's own decision (Experiment 1) and feedback from observing others' decisions (Experiment 2) on electroencephalograph responses to winning and losing money with and without betting. Irrespective of whether the betting is self-generated or simply observed, the cognitive evaluation of the outcome evoked feedback-related negativity, indicating that one's own experience and vicarious experience give rise to the same neural response. These results indicate that participants were more sensitive to loss when it was personally relevant, irrespective of whether that loss was associated with betting. However, when observing others' losses, participants showed stronger negative responses when the losses were associated with betting. PMID- 26379061 TI - Reactions of Methanesulfonic Acid with Amines and Ammonia as a Source of New Particles in Air. AB - New particle formation (NPF) from gaseous precursors as a significant source of aerosol needs to be better understood to accurately predict the impacts on visibility, climate change, and human health. While ternary nucleation of sulfuric acid, amines/NH3, and water is recognized as a significant driver for NPF, increasing evidence suggests a contribution from methanesulfonic acid (MSA) and amines under certain conditions. Here we report the formation of particles 2.5-10 nm in diameter from the reactions of MSA with methylamine (MA), dimethylamine (DMA), and NH3 at reaction times of 2.3-7.8 s in a flow reactor and compare these particles with those previously reported to be formed from reaction with trimethylamine (TMA). The effects of water vapor and concentrations of gaseous precursors on the particle number concentration and particle size were studied. The presence of water significantly enhances particle formation and growth. Under similar experimental conditions, particle number concentrations decrease in the order MA ? TMA ~ DMA ? NH3, where NH3 is 2-3 orders of magnitude less efficient than DMA. Quantum chemical calculations of likely intermediate clusters were carried out to provide insights into the role of water and the different capacities of amines/NH3 in particle formation. Both gas-phase basicity and hydrogen-bonding capacity of amines/NH3 contribute to the potential for particles to form and grow. Our results indicate that, although amines typically have concentrations 1-3 orders of magnitude lower than that of NH3 in the atmosphere, they still play an important role in driving NPF. PMID- 26379062 TI - Genetic and Environmental Overlap Between Childhood Maltreatment and Adult Physical Health. AB - Past research demonstrates a phenotypic relationship between childhood maltreatment and adult health problems. Explanations of this association usually point to either: (a) a direct causal link, whereby exposure to early stress disrupts biological functioning during sensitive periods of development; or (b) an indirect effect operating through socioeconomic attainment, poor health behaviors, or some other pathway leading from childhood to adulthood. The current study examined whether the association between childhood maltreatment and adult health reflects genetic or environmental mediation. Using a large sample of adult American twins, we separately estimated univariate biometric models of child maltreatment and adult physical health, followed by a bivariate biometric model to estimate genetic and environmental correlations between the two variables. We found that a summary count of chronic health conditions shared non-trivial genetic overlap with childhood maltreatment. Our results have implications for understanding the relationship between maltreatment and health as one of active interplay rather than a simple cause and effect model that views maltreatment as an exogenous shock. PMID- 26379063 TI - Genetic and Environmental Effects on Weight, Height, and BMI Under 18 Years in a Chinese Population-Based Twin Sample. AB - This study examined the genetic and environmental effects on variances in weight, height, and body mass index (BMI) under 18 years in a population-based sample from China. We selected 6,644 monozygotic and 5,969 dizygotic twin pairs from the Chinese National Twin Registry (CNTR) aged under 18 years (n = 12,613). Classic twin analyses with sex limitation were used to estimate the genetic and environmental components of weight, height, and BMI in six age groups. Sex limitation of genetic and shared environmental effects was observed, especially when puberty begins. Heritability for weight, height, and BMI was low at 0-2 years old (less than 20% for both sexes) but increased over time, accounting for half or more of the variance in the 15-17 year age group for boys. For girls, heritabilities for weight, height and BMI was maintained at approximately 30% after puberty. Common environmental effects on all body measures were high for girls (59-87%) and presented a small peak during puberty. Genetics appear to play an increasingly important role in explaining the variation in weight, height, and BMI from early childhood to late adolescence, particularly in boys. Common environmental factors exert their strongest and most independent influence specifically in the pre-adolescent period and more significantly in girls. These findings emphasize the need to target family and social environmental interventions in early childhood years, especially for females. Further studies about puberty-related genes and social environment are needed to clarify the mechanism of sex differences. PMID- 26379066 TI - Comparison of NiS2 and alpha-NiS hollow spheres for supercapacitors, non enzymatic glucose sensors and water treatment. AB - NiS2 hollow spheres are successfully prepared by a one-step template free method. Meanwhile, alpha-NiS hollow spheres can also be synthesized via the calcination of the pre-obtained NiS2 hollow spheres at 400 degrees C for 1 h in air. The electrochemical performances of the as-prepared NiS2 and alpha-NiS hollow sphere products are evaluated. When used for supercapacitors, compared with NiS2 hollow spheres, the alpha-NiS hollow sphere electrode shows a large specific capacitance of 717.3 F g(-1) at 0.6 A g(-1) and a good cycle life. Furthermore, NiS2 and alpha-NiS hollow spheres are successfully applied to fabricate non-enzymatic glucose sensors. In particular, the alpha-NiS hollow spheres exhibit good catalytic activity for the oxidation of glucose, a fast amperometric response time of less than 5 s, and the detection limit is estimated to be 0.08 MUM. More importantly, compared with other normally co-existing interfering species, such as ascorbic acid, uric acid and dopamine, the electrode modified with alpha-NiS hollow spheres shows good selectivity. Moreover, the alpha-NiS hollow spheres also present good capacity to remove Congo red organic pollutants from wastewater by their surface adsorption ability. PMID- 26379067 TI - Prevalence of Anal HPV Infection Among HIV-Positive Men Who Have Sex With Men in India. AB - BACKGROUND: India has a large population of HIV-positive individuals, including men who have sex with men (MSM), and the incidence of human papillomavirus (HPV) related cancers is high. In developed countries, HIV-positive MSM exhibit the highest prevalence of anal HPV infection and incidence of anal cancer. Little is known about anal HPV infection in HIV-positive Indian MSM. METHODS: We evaluated 300 HIV-positive MSM from 2 cities in India. Men were tested for anal HPV infection using L1-HPV DNA polymerase chain reaction with probes specific for 29 types and a mixture of 10 additional types. CD4 level and plasma HIV viral load were measured. Participants completed an interviewer-administered questionnaire including a sexual history. RESULTS: The prevalence of anal HPV was 95% (95% confidence interval: 91% to 97%). The 3 most common types were HPV 35 (20%), HPV 16 (13%), and HPV 6/11 (13%). History of taking antiretroviral medications decreased risk of anal HPV 16 infection [relative risk (RR): 0.6 (0.4-1.0)]. Having an increased number of vaginal sex partners lowered risk of any anal HPV infection. Ever having receptive sex increased risk of any anal HPV [RR: 1.2 (1.1 1.4)] and anal HPV 16 [RR: 6.5 (1.8-107)]. CONCLUSIONS: Almost all Indian HIV positive MSM had anal HPV infection. The prevalence of HPV 16 was lower and the prevalence of other oncogenic HPV types was higher than in similar populations in North America and Europe. Vaccine-based prevention strategies for HPV infection in India should consider potential differences in HPV type distribution among HIV infected MSM when designing interventions. PMID- 26379068 TI - Immunization of HIV-1-Infected Persons With Autologous Dendritic Cells Transfected With mRNA Encoding HIV-1 Gag and Nef: Results of a Randomized, Placebo-Controlled Clinical Trial. AB - BACKGROUND: HIV-1 eradication may require reactivation of latent virus along with stimulation of HIV-1-specific immune responses to clear infected cells. Immunization with autologous dendritic cells (DCs) transfected with viral mRNA is a promising strategy for eliciting HIV-1-specific immune responses. We performed a randomized controlled clinical trial to evaluate the immunogenicity of this approach in HIV-1-infected persons on antiretroviral therapy. METHODS: Fifteen participants were randomized 2:1 to receive intradermal immunization with HIV-1 Gag- and Nef-transfected DCs (vaccine) or mock-transfected DCs (placebo) at weeks 0, 2, 6, and 10. All participants also received DCs pulsed with keyhole limpet hemocyanin (KLH) to assess whether responses to a neo-antigen could be induced. RESULTS: After immunization, there were no differences in interferon-gamma enzyme linked immunospot responses to HIV-1 Gag or Nef in the vaccine or placebo group. CD4 proliferative responses to KLH increased 2.4-fold (P = 0.026) and CD8 proliferative responses to KLH increased 2.5-fold (P = 0.053) after vaccination. There were increases in CD4 proliferative responses to HIV-1 Gag (2.5-fold vs. baseline, 3.4-fold vs. placebo, P = 0.054) and HIV-1 Nef (2.3-fold vs. baseline, 6.3-fold vs. placebo, P = 0.009) among vaccine recipients, but these responses were short-lived. CONCLUSION: Immunization with DCs transfected with mRNA encoding HIV-1 Gag and Nef did not induce significant interferon-gamma enzyme linked immunospot responses. There were increases in proliferative responses to HIV-1 antigens and to a neo-antigen, KLH, but the effects were transient. Dendritic cell vaccination should be optimized to elicit stronger and long lasting immune responses for this strategy to be effective as an HIV-1 therapeutic vaccine. PMID- 26379069 TI - Reassuring Birth Outcomes With Tenofovir/Emtricitabine/Efavirenz Used for Prevention of Mother-to-Child Transmission of HIV in Botswana. AB - BACKGROUND: Before introduction of tenofovir/emtricitabine/efavirenz (TDF/FTC/EFV), 3-drug antiretroviral therapy (ART) was associated with increased adverse birth outcomes when used for prevention of mother-to-child HIV transmission (PMTCT) in Botswana. METHODS: We extracted obstetric records from all women at the 2 largest maternities in Botswana from 2009-2011 when Botswana National Guidelines recommended zidovudine (ZDV) from 28 weeks gestational age (GA) for CD4 >=350 and ART for CD4 <350, and again in 2013-2014 after implementation of TDF/FTC/EFV for prevention of mother-to-child HIV transmission regardless of CD4 or GA. We compared the use of TDF/FTC/EFV in pregnancy with other 3-drug ART regimens, and with initiation of ZDV, among women with similar CD4 cell counts. Outcomes included small for gestational age (SGA), preterm delivery (PTD) (<37 weeks GA), and stillbirths (SB). RESULTS: Among 9445 HIV infected women delivering during the study period, 170 were on TDF/FTC/EFV at conception and 1468 initiated TDF/FTC/EFV during pregnancy. Adverse birth outcomes were high overall (3% SB, 21% PTD, and 18% SGA) and among women receiving TDF/FTC/EFV (3% SB, 22% PTD, and 12% SGA). There was no difference in PTD or SB among women initiating TDF/FTC/EFV compared with ZDV or other 3-drug ART, but initiating TDF/FTC/EFV was associated with fewer SGA infants than other 3-drug ART (adjusted odds ratio: 0.4, 95% confidence interval: 0.2 to 0.7). CONCLUSIONS: Adverse birth outcomes remain high among HIV-infected women. TDF/FTC/EFV was at least as safe as other ART and associated with fewer SGA infants when initiated during pregnancy. Larger studies are needed to evaluate birth outcomes and congenital abnormalities among women on TDF/FTC/EFV at conception. PMID- 26379071 TI - Enhanced Photocatalytic Activity of Ultrathin Ba5Nb4O15 Two-Dimensional Nanosheets. AB - Anisotropic two-dimensional (2D) nanosheets of the layered perovskite, Ba5Nb4O15, with thicknesses of 5-10 nm and lateral sizes of 300-1200 nm, were synthesized by a hydrothermal route. The influences of the 2D morphology of the material on the crystal and electronic structures, light absorption properties, and photocatalytic activity were investigated. The ultrathin nanosheets showed much enhanced photocatalytic activity compared to both thick nanosheets (~30 nm) and micrometer-sized particles for the evolution of H2 from water splitting under UV light illumination. This enhanced activity is predominantly attributed to the larger surface area, higher optical absorption, and charge separation ability of the 2D nanosheet, which results from the variation of the local crystal structure arising from the ultrathin morphology of the Ba5Nb4O15. PMID- 26379070 TI - Hormonal Contraception, Pregnancy, Breastfeeding, and Risk of HIV Disease Progression Among Zambian Women. AB - BACKGROUND: Some studies suggest that hormonal contraception, pregnancy, and/or breastfeeding may influence rates of HIV disease progression. METHODS: From 1994 to 2012, HIV discordant couples recruited at couples' voluntary HIV counseling and testing centers in Lusaka were followed 3-monthly. Multivariate survival analyses explored associations between time-varying contraception, pregnancy, and breastfeeding and 2 outcomes among HIV-positive women: (1) time to death and (2) time to antiretroviral treatment (ART) initiation. RESULTS: Among 1656 female seropositive, male seronegative couples followed for 3359 person-years (PY), 224 women died [6.7/100 PY; 95% confidence interval (CI): 5.8 to 7.6]. After 2003, 290 women initiated ART (14.5/100 PY; 95% CI: 12.9 to 16.2). In a multivariate model of time to death, hormonal implant [adjusted hazard ratio (aHR) = 0.30; 95% CI: 0.10 to 0.98] and injectable (aHR = 0.59; 95% CI: 0.36 to 0.97) were significantly protective relative to nonhormonal method use, whereas oral contraceptive pill (OCP) use was not (aHR = 1.08; 95% CI: 0.74 to 1.57) controlling for baseline HIV disease stage, time-varying pregnancy, time-varying breastfeeding, and year of enrollment. In a multivariate model of time-to-ART initiation, implant was significantly protective (aHR = 0.54; 95% CI: 0.31 to 0.95), whereas OCP (aHR = 0.70; 95% CI: 0.44 to 1.10) and injectable (aHR = 0.85; 95% CI: 0.55 to 1.32) were not relative to nonhormonal method use controlling for variables above, woman's age, and literacy. Pregnancy was not significantly associated with death (aHR = 1.07; 95% CI: 0.68 to 1.66) or ART initiation (aHR = 1.24; 95% CI: 0.83 to 1.86), whereas breastfeeding was protective for death (aHR = 0.34; 95% CI: 0.19 to 0.62) and ART initiation (aHR = 0.49; 95% CI: 0.29 to 0.85). CONCLUSIONS: Hormonal implants and injectables significantly predicted lower mortality; implants were protective for ART initiation. OCPs and pregnancy were not associated with death or ART initiation, whereas breastfeeding was protective for both. Findings from this 18-year cohort study suggest that (1) HIV positive women desiring pregnancy can be counseled to do so and breastfeed and (2) all effective contraceptive methods, including injectables and implants, should be promoted to prevent unintended pregnancy. PMID- 26379072 TI - Migraine and Suicidal Behaviors: A Systematic Literature Review. AB - OBJECTIVE: The aim of this systematic review was to provide a picture of suicidality (suicide ideation and behavior, both fatal and nonfatal) among indviduals with migraine. BACKGROUND: Migraine is a leading cause of disability around the world. Migraine may manifest with a number of symptoms, ranging from severe headaches to neurological sensory disturbances. Comorbid psychological conditions, such as depression, have also been linked to chronic migraine. DATA SOURCES: Articles were retrieved from SCOPUS, PubMed, Proquest, and Web of Science. SEARCH TERMS: Suicid* AND migrain* in English-language peer-reviewed journals between January 1, 1966 and December 31, 2014. ELIGIBILITY CRITERIA: Original research papers providing empirical evidence about the potential link between migraine and suicidal behaviors. RESULTS: Initial search identified 510 papers; the titles and abstracts of 360 unique results were examined for their relevance to the combination of migraine and suicidality. In total, 17 papers reporting original empirical analyses were included in this review. CONCLUSIONS: Research has empirically documented a link between migraine and suicide ideation and behavior, particularly concerning the subtype of migraine with aura. Overall, nonfatal suicidal behavior among people with migraine has primarily been investigated, with only 2 studies analyzing suicide mortality. In addition, majority of studies originated from the United States or Canada (n=10). Future research should thoroughly define migraine and investigate link between migraine and suicide mortality. PMID- 26379073 TI - Pain and Depressive Symptoms in Primary Care: Moderating Role of Positive and Negative Affect. AB - OBJECTIVES: Pain and its disruptive impact on daily life are common reasons that patients seek primary medical care. Pain contributes strongly to psychopathology, and pain and depressive symptoms are often comorbid in primary care patients. Not all those who experience pain develop depression, suggesting that the presence of individual-level characteristics, such as positive and negative affect, that may ameliorate or exacerbate this association. METHODS: We assessed the potential moderating role of positive and negative affect on the pain-depression linkage. In a sample of 101 rural, primary care patients, we administered the Brief Pain Inventory, NEO Personality Inventory-Revised positive and negative affect subclusters, and the Center for Epidemiology Scale for Depression. RESULTS: In moderation models, covarying age, sex, and ethnicity, we found that positive affect, but not negative affect, was a significant moderator of the relation between pain intensity and severity and depressive symptoms. DISCUSSION: The association between pain and depressive symptoms is attenuated when greater levels of positive affects are present. Therapeutic bolstering of positive affect in primary care patients experiencing pain may reduce the risk for depressive symptoms. PMID- 26379074 TI - Psychosocial and Functional Outcomes in Youth With Chronic Sickle Cell Pain. AB - OBJECTIVE: To describe chronic pain-pain that is present most days per month over the past 3 months-in youth with sickle cell disease (SCD). This study characterized differences in functional outcomes, psychosocial characteristics, and health care utilization for youth with SCD across 3 groups based on pain frequency: chronic pain, episodic pain, and no SCD pain in the past month. MATERIALS AND METHODS: Children and adolescents (aged 8 to 18 y) with SCD and their parents (n=100) completed measures of functional disability, health-related quality of life, depressive symptoms, pain catastrophizing, pain beliefs, and health care utilization during an outpatient comprehensive sickle cell clinic appointment. On the basis of pain frequency and duration, patients were categorized as follows: (1) chronic (>=3 d of pain per week in the past month lasting >=3 mo; range, 12 to 31 d/mo), (2) episodic (<3 d of pain per week for the past month; range, 1 to 10 d/mo), and (3) no SCD pain in the past month. RESULTS: Consistent with other pediatric chronic pain conditions, youth characterized as having chronic sickle pain (n=40) reported significantly greater functional disability, depressive symptoms, and inpatient admissions for pain relative to patients characterized with having episodic SCD pain (n=40) or no SCD pain (n=20). The chronic and episodic pain groups had comparable levels of pain intensity, pain catastrophizing, and quality of life. DISCUSSION: Specific definitions and criteria for chronic sickle pain in youth are needed. Identifying risk and protective factors related to the transition from acute to chronic pain is important to facilitate improved psychosocial functioning. PMID- 26379075 TI - Effects of Alzheimer Disease on the Facial Expression of Pain. AB - OBJECTIVES: Facial expression may be a surrogate marker of pain in Alzheimer disease (AD) when self-report of pain is compromised. Recent studies have demonstrated increased pain sensitivity in AD; however, experimental pain studies analyzing facial expressions in AD are limited and report inconsistent results. The aims of this study were to examine facial expression of pain in AD patients and its relationship to sum-scored measures of multiple pain behavioral domains and subjective pain ratings. MATERIALS AND METHODS: The Facial Action Coding System (FACS) was used to characterize facial expressions in 35 AD patients and 33 healthy seniors during pressure algometry. To improve pain specificity, facial responses were categorized as pain-relevant or pain-irrelevant before group analyses. We also assessed the relationship of AD severity to differential facial responsiveness by correlating FACS-based results with clinical pain scales (portions of the Pain Assessment in Advanced Dementia scale and the Faces Pain Scale-Revised [FPS-R]). RESULTS: No significant relationship was found between AD severity and FACS scores. Pain-relevant, but not irrelevant, FACS scores were increased in AD patients compared with seniors without AD. Pain Assessment in Advanced Dementia scale stimulus-response slopes were correlated with those of pain-relevant FACS and FPS-R in both the groups. Pain-relevant FACS slopes showed no relationship with those of the FPS-R in either group. DISCUSSION: Pain sensitivity is increased across all severities of AD when measured using the FACS. Clinical observational pain scales support the relevance of facial expression as a partial compensatory pain communication modality for AD. However, measures of pain behavior that sum across objective coding of several domains provide a better indicator of subjective pain than measures of facial expression alone. PMID- 26379076 TI - Characterization of Migraineurs Having Allodynia: Results of a Large Population based Study. AB - OBJECTIVE: Allodynia reflects the clinical correlate of central sensitization, but it is usually neglected in clinical headache management. We aimed to report the prevalence and previously unnoticed associations of allodynia in migraineurs by a nationwide face-to-face questionnaire-based study by physicians. METHODS: A total of 5323 households were examined for headache according to the diagnostic criteria of International Classification of Headache Disorders-II. Detailed headache features, premonitory signs, demographics, socio-economic status, and hormonal status of female individuals were analyzed with regard to the presence of allodynia in patients with definite migraine. RESULTS: Allodynia was present in 61.1% of migraineurs in the general population of Turkey. The duration and severity of attacks (P<0.0001), photophobia (P=0.001), phonophobia, and also osmophobia (P<0.0001), as well as premonitory signs (P=0.018), showed significant associations with allodynia. Migraineurs with aura or family history of migraine more often reported allodynia in comparison with those without (P=0.001 and 0.028, respectively). Allodynic migraineurs had a higher rate of physician consults and high levels on the Migraine Disability Assessment questionnaire, reflecting increased burden of headache. Furthermore, migraineurs with allodynia had high probability of attacks close to menses. Migraine improved during pregnancy, but it worsened after menopause or during oral contraceptive use in individuals experiencing allodynia when compared with those without allodynia. DISCUSSION: The duration, severity, and disability of migraine attacks, photophobia, phonophobia, and osmophobia, as well as premonitory signs, showed significant associations with allodynia in the general population. Moreover, migraineurs with aura or family history of migraine more often reported allodynia, and allodynic migraneurs were more sensitive to hormonal changes. Allodynia, which seems to indicate higher tendency to central sensitization, should be implemented in daily headache practice to predict the prognosis and high levels of migraineous involvement. PMID- 26379077 TI - Chronic Widespread Back Pain is Distinct From Chronic Local Back Pain: Evidence From Quantitative Sensory Testing, Pain Drawings, and Psychometrics. AB - OBJECTIVES: Whether chronic localized pain (CLP) and chronic widespread pain (CWP) have different mechanisms or to what extent they overlap in their pathophysiology is controversial. The study compared quantitative sensory testing profiles of nonspecific chronic back pain patients with CLP (n=48) and CWP (n=29) with and fibromyalgia syndrome (FMS) patients (n=90) and pain-free controls (n = 40). MATERIALS AND METHODS: The quantitative sensory testing protocol of the "German-Research-Network-on-Neuropathic-Pain" was used to measure evoked pain on the painful area in the lower back and the pain-free hand (thermal and mechanical detection and pain thresholds, vibration threshold, pain sensitivity to sharp and blunt mechanical stimuli). Ongoing pain and psychometrics were captured with pain drawings and questionnaires. RESULTS: CLP patients did not differ from pain-free controls, except for lower pressure pain threshold (PPT) on the back. CWP and FMS patients showed lower heat pain threshold and higher wind-up ratio on the back and lower heat pain threshold and cold pain threshold on the hand. FMS showed lower PPT on back and hand, and higher comorbidity of anxiety and depression and more functional impairment than all other groups. DISCUSSION: Even after long duration CLP presents with a local hypersensitivity for PPT, suggesting a somatotopically specific sensitization of nociceptive processing. However, CWP patients show widespread ongoing pain and hyperalgesia for different stimuli that is generalized in space, suggesting the involvement of descending control systems, as also suggested for FMS patients. Because mechanisms in nonspecific chronic back pain with CLP and CWP differ, these patients should be distinguished in future research and allocated to different treatments. PMID- 26379078 TI - PTEN loss in circulating tumour cells correlates with PTEN loss in fresh tumour tissue from castration-resistant prostate cancer patients. AB - BACKGROUND: PTEN gene loss occurs frequently in castration-resistant prostate cancer (CRPC) and may drive progression through activation of the PI3K/AKT pathway. Here, we developed a novel CTC-based assay to determine PTEN status and examined the correlation between PTEN status in CTCs and matched tumour tissue samples. METHODS: PTEN gene status in CTCs was evaluated on an enrichment-free platform (Epic Sciences) by fluorescence in situ hybridisation (FISH). PTEN status in archival and fresh tumour tissue was evaluated by FISH and immunohistochemistry. RESULTS: Peripheral blood was collected from 76 patients. Matched archival and fresh cancer tissue was available for 48 patients. PTEN gene status detected in CTCs was concordant with PTEN status in matched fresh tissues and archival tissue in 32 of 38 patients (84%) and 24 of 39 patients (62%), respectively. CTC counts were prognostic (continuous, P=0.001). PTEN loss in CTCs associated with worse survival in univariate analysis (HR 2.05; 95% CI 1.17-3.62; P=0.01) and with high lactate dehydrogenase (LDH) in metastatic CRPC patients. CONCLUSIONS: Our results illustrate the potential use of CTCs as a non-invasive, real-time liquid biopsy to determine PTEN gene status. The prognostic and predictive value of PTEN in CTCs warrants investigation in CRPC clinical trials of PI3K/AKT-targeted therapies. PMID- 26379081 TI - Expectancy biases in fear and anxiety and their link to biases in attention. AB - Healthy individuals often exhibit prioritized processing of aversive information, as manifested in enhanced orientation of attention to threatening stimuli compared with neutral items. In contrast to this adaptive behavior, anxious, fearful, and phobic individuals show exaggerated attention biases to threat. In addition, they overestimate the likelihood of encountering their feared stimulus and the severity of the consequences; both are examples of expectancy biases. The co-occurrence of attention and expectancy biases in fear and anxiety raises the question about causal influences. Herein, we summarize findings related to expectancy biases in fear and anxiety, and their association with attention biases. We suggest that evidence calls for more comprehensive research strategies in the investigation of mutual influences between expectancy and attention biases, as well as their combined effects on fear and anxiety. Moreover, both types of bias need to be related to other types of distorted information processing commonly observed in fear and anxiety (e.g., memory and interpretation biases). Finally, we propose new research directions that may be worth considering in developing more effective treatments for anxiety disorders. PMID- 26379079 TI - Impact of alcohol drinking on gastric cancer development according to Helicobacter pylori infection status. AB - BACKGROUND: Helicobacter pylori are major carcinogen of gastric cancer, but the associations among gastric cancer, H. pylori infection status, and alcohol consumption are not fully described. This study aimed to clarify how H. pylori infection status affects the association between alcohol consumption and gastric cancer risk. METHODS: We selected 949 case-cohort participants from the 18,863 Korean Multi-center Cancer Cohort (KMCC) populations. Gastric cancer incidence inside and outside of the subcohort were 12 and 254 cases, respectively. Seropositivities for CagA, VacA, and H. pylori infection were determined by performing immunoblot assays. Weighted Cox regression models were used to calculate hazard ratios and 95% confidence intervals (CIs). RESULTS: Relative to non-drinking, heavy drinking (?7 times a week), and binge drinking (?55 g alcohol intake per occasion) showed a 3.48-fold (95% CI, 1.13-10.73) and 3.27-fold (95% CI, 1.01-10.56) higher risk in subjects not previously infected by H. pylori. There was no significant association between drinking pattern and gastric cancer risk in H. pylori IgG seropositive subjects. An increased risk for gastric cancer in heavy- and binge-drinking subjects were also present in subjects not infected by CagA- or VacA-secreting H. pylori. CONCLUSIONS: Heavy and binge alcohol consumption is an important risk factor related to an increasing incidence of gastric cancer in a population not infected by H. pylori. PMID- 26379082 TI - Molecular simulation study of feruloyl esterase adsorption on charged surfaces: effects of surface charge density and ionic strength. AB - The surrounding conditions, such as surface charge density and ionic strength, play an important role in enzyme adsorption. The adsorption of a nonmodular type A feruloyl esterase from Aspergillus niger (AnFaeA) on charged surfaces was investigated by parallel tempering Monte Carlo (PTMC) and all-atom molecular dynamics (AAMD) simulations at different surface charge densities (+/-0.05 and +/ 0.16 C.m(-2)) and ionic strengths (0.007 and 0.154 M). The adsorption energy, orientation, and conformational changes were analyzed. Simulation results show that whether AnFaeA can adsorb onto a charged surface is mainly controlled by electrostatic interactions between AnFaeA and the charged surface. The electrostatic interactions between AnFaeA and charged surfaces are weakened when the ionic strength increases. The positively charged surface at low surface charge density and high ionic strength conditions can maximize the utilization of the immobilized AnFaeA. The counterion layer plays a key role in the adsorption of AnFaeA on the negatively charged COOH-SAM. The native conformation of AnFaeA is well preserved under all of these conditions. The results of this work can be used for the controlled immobilization of AnFaeA. PMID- 26379080 TI - Prognostic impact of discrepant Ki67 and mitotic index on hormone receptor positive, HER2-negative breast carcinoma. AB - BACKGROUND: Inconsistencies between mitotic index (MI) and Ki67 measures have been identified in many breast tumour samples. The aim of this study was to describe the prognosis of hormone receptor-positive (HR+) HER2- tumours having discrepant MI and Ki67. METHODS: We included a cohort of breast cancer patients initially treated by surgery between 2001 and 2005 in the Institut Curie. Breast cancer-specific survival (BCSS) and disease-free survival (DFS) were analysed according to three proliferation groups: high MI/high Ki67 (MI=3, Ki67>20%), low MI/low Ki67 (MI<3, Ki67?20%) and discrepant (high MI/low Ki67 or low MI/high Ki67). RESULTS: Among the 1430 patients, 19.6% had discrepant Ki67 and MI, 11.6% had high markers and 68.8% had low markers. The 5-year BCSS was 95.8%, 95% CI (0.93-0.98) in the discrepant group, 99.3%, 95% CI (0.993-0.999) in the low proliferation group and 91.8%, 95% CI (0.88-0.96) in the high-proliferation group. In multivariate analysis, the survival of the discrepant group was lower than that of the low-proliferation group: BCSS hazard ratio (HR)=3.01 (1.32-6.84; P=0.008) and DFS HR=2.07, 95% CI (1.31-3.26; P=0.002). Among grade 2 tumours in multivariate analysis, DFS of the discrepant group was lower than that of the low MI/low Ki67 group: HR=1.98, 95% CI (1.14-3.46), P=0.02. Regarding BCSS, the obtained results were similar. CONCLUSION: The prognosis of patients with discrepant MI and Ki67 appears intermediate between that of low MI/low Ki67 and high MI/high Ki67 groups. These markers should be jointly analysed to clarify prognosis. PMID- 26379083 TI - Niche Mimicking for Selection and Enrichment of Liver Cancer Stem Cells by Hyaluronic Acid-Based Multilayer Films. AB - Cancer stem cells (CSCs) represent a subpopulation of tumor cells that exhibit capacities for self-renewal, tumor initiation, disease relapse or metastasis, and resistance to chemotherapy and radiotherapy. However, the major obstacle associated with the use of CSCs is the difficulty in their isolation and enrichment. According to recent studies, CSCs share similar properties with normal stem cells, and it has been observed that hyaluronan (HA) plays a key factor in CSCs niches and that HA-mediated CD44 interaction promotes tumor progression. Therefore, HA-based multilayer films were used to fabricate sequential surface properties variation and to mimic CSC niches. A quartz crystal microbalance was used to investigate the layer-by-layer adsorption of PAH/HA multilayer films. Colony formation was observed on a series of poly(allylamine hydrochloride) PAH/HA multilayer films, and cytotoxicity and cell viability were evaluated by MTT, LDH and live/dead assay. It was observed that the cells isolated from (PAH/HA)3 displayed the best colony formation ability and that the expression of CD133/CD44 double positive cells was up-regulated to approximately 70% after 7 days of culture. Furthermore, the cells isolated from (PAH/HA)3 displayed higher chemo-resistance than the control group. The stem-cell-related genes expression of selected cells from (PAH/HA)3 after 7 days of culture was significantly different from that of the control group. In conclusion, this study provides a label-free selection and enrichment system that could serve as a new strategy for the future development of CSC selection and drug evaluation in cancer therapy. PMID- 26379084 TI - How reliable are self-reports of HIV status disclosure? Evidence from couples in Malawi. AB - INTRODUCTION: The majority of research on human immunodeficiency virus (HIV) disclosure utilizes the perspective from a single individual, which cannot be substantiated in the absence of supporting data such as from a primary partner. OBJECTIVES: The objectives of this study were to evaluate: (1) the extent to which self-reported HIV disclosure was confirmed by a primary partner; (2) individual and relationship-level predictors of self-reported versus confirmed disclosure; and (3) whether confirmed disclosure was a stronger predictor of correctly assessing a partner's HIV status compared to self-reported disclosure. METHODS: As part of an 8-wave longitudinal study from 2009 to 2011 in southern Malawi, 366 individuals (183 couples) were interviewed about their primary relationship (wave 3), individually tested for HIV (wave 4), and then asked whether they disclosed to their primary partner (wave 5). RESULTS: While 93% of respondents reported that they disclosed, only 64% of respondents had confirmed reports from their partner. Having communicated with partner about HIV was positively associated with self-reported disclosure; this association remained significant but became more precise in the models for confirmed disclosure. Confirmed disclosure, but not self-report, was a significant predictor of correctly assessing a partner's HIV status. Being male, having lower perceived partner infidelity, having higher relationship unity, and testing HIV-negative were positively and significantly associated with correct assessment. Dyadic data from two partners provide an improved measure of disclosure as compared to a single individual's self-report and could be used to identify behavioral and biomedical opportunities to prevent HIV transmission within couples. PMID- 26379085 TI - Practical designs for Phase I combination studies in oncology. AB - Phase I trials evaluating the safety of multidrug combinations are becoming more common in oncology. Despite the emergence of novel methodology in the area, it is rare that innovative approaches are used in practice. In this article, we review three methods for Phase I combination studies that are easy to understand and straightforward to implement. We demonstrate the operating characteristics of the designs through illustration in a single trial, as well as through extensive simulation studies, with the aim of increasing the use of novel approaches in Phase I combination studies. Design specifications and software capabilities are also discussed. PMID- 26379086 TI - Numerical study of variable-density flow and transport in unsaturated-saturated porous media. AB - Dense contaminant or solute transport in the unsaturated-saturated aquifer commonly exists in the natural environment. However, the influence of hydraulic properties of the unsaturated soil on penetration process of variable density flow in an unsaturated-saturated aquifer system is rarely investigated. In this study, a variable density, variably saturated flow and transport model based on FEFLOW is used to systematically investigate the penetration process of the solute through the unsaturated-saturated aquifer system, with a focus on the influence of the hydraulic parameters of the unsaturated soil on the penetration process. Vertical center of mass, and its speed and acceleration, are used to identify different stages of the penetration process through the unsaturated saturated aquifer. The hydraulic parameters in the van Genuchten-Mualem model (VGM) affect the water content distribution in the unsaturated zone, subsequently the penetration time through the unsaturated zone. Through influencing the thickness of the transition zone (0.1-0.9 maximum concentration of the plume) when the plume reaches the water table, the hydraulic parameters affect the accumulation time of the solute at the boundary layer in the saturated zone. Thus, the process in not only the unsaturated but also the saturated zones is influenced by the change of the hydraulic properties of the unsaturated zone. Furthermore, the results show that the instabilities start to occur at the zone with high water content (90% of maximum saturation) in the capillary fringe. Freshwater intrudes into the zone with high water content when fingers are completely developed at the entire system. The length of freshwater intrusion above the water table has a negative correlation with the fitting parameter alpha in the VGM model. The influence of the density difference of the solute on the penetration processes is insignificant in the unsaturated zone but significant in the saturated zone. Sensitive analysis for the hydraulic properties of the unsaturated soil on the penetration process shows that pore size distribution index is the main factor influencing the penetration time through the unsaturated zone, the penetration time through the entire aquifer, the accumulation time at the boundary layer, and the development time of the fingers. Two other parameters, fitting parameter alpha and residual saturation, have minor effects. PMID- 26379087 TI - How does it feel to lack a sense of boundaries? A case study of a long-term mindfulness meditator. AB - This paper discusses the phenomenological nature of the sense of boundaries (SB), based on the case of S, who has practiced mindfulness in the Satipathana and Theravada Vipassana traditions for about 40years and accumulated around 20,000h of meditative practice. S's unique abilities enable him to describe his inner lived experience with great precision and clarity. S was asked to shift between three different stages: (a) the default state, (b) the dissolving of the SB, and (c) the disappearance of the SB. Based on his descriptions, we identified seven categories (with some overlap) that alter during the shifts between these stages, including the senses of: (1) internal versus external, (2) time, (3) location, (4) self, (5) agency (control), (6) ownership, and (7) center (first-person egocentric-bodily perspective). Two other categories, the touching/touched structure and one's bodily feelings, do not fade away completely even when the sense-of-boundaries disappears. PMID- 26379088 TI - Mutational bias of Turnip Yellow Mosaic Virus in the context of host anti-viral gene silencing. AB - Plant Dicer-like (DCL) enzymes exhibit a GC-preference during anti-viral post transcriptional gene silencing (PTGS), delivering an evolutionary selection pressure resulting in plant viruses with GC-poor genomes. However, some viruses, e.g. Turnip Yellow Mosaic Virus (TYMV, genus Tymovirus) have GC-rich genomes, raising the question as to whether or not DCL derived selection pressure affects these viruses. In this study we analyzed the virus-derived small interfering RNAs from TYMV-infected leaves of Brassica juncea showed that the TYMV population accumulated a mutational bias with AU replacing GC (GC-AU), demonstrating PTGS pressure. Interestingly, at the highly polymorphic sites the GC-AU bias was no longer observed. This suggests the presence of an unknown mechanism preventing mutational drift of the viral population and maintaining viral genome stability, despite the host PTGS pressure. PMID- 26379089 TI - RNAP II processivity is a limiting step for HIV-1 transcription independent of orientation to and activity of endogenous neighboring promoters. AB - Since HIV-1 has a propensity to integrate into actively expressed genes, transcriptional interference from neighboring host promoters has been proposed to contribute to the establishment and maintenance HIV-1 latency. To gain insights into how endogenous promoters influence HIV-1 transcription we utilized a set of inducible T cell lines and characterized whether there were correlations between expression of endogenous genes, provirus and long terminal repeat architecture. We show that neighboring promoters are active but have minimal impact on HIV-1 transcription, in particular, expression of the endogenous gene did not prevent expression of HIV-1 following induction of latent provirus. We also demonstrate that releasing paused RNAP II by diminishing negative elongation factor (NELF) is sufficient to reactivate transcriptionally repressed HIV-1 provirus regardless of the integration site and orientation of the provirus suggesting that NELF mediated RNAP II pausing is a common mechanism of maintaining HIV-1 latency. PMID- 26379090 TI - RNA helicase MOV10 functions as a co-factor of HIV-1 Rev to facilitate Rev/RRE dependent nuclear export of viral mRNAs. AB - Human immunodeficiency virus type 1 (HIV-1) exploits multiple host factors during its replication. The REV/RRE-dependent nuclear export of unspliced/partially spliced viral transcripts needs the assistance of host proteins. Recent studies have shown that MOV10 overexpression inhibited HIV-1 replication at various steps. However, the endogenous MOV10 was required in certain step(s) of HIV-1 replication. In this report, we found that MOV10 potently enhances the nuclear export of viral mRNAs and subsequently increases the expression of Gag protein and other late products through affecting the Rev/RRE axis. The co immunoprecipitation analysis indicated that MOV10 interacts with Rev in an RNA independent manner. The DEAG-box of MOV10 was required for the enhancement of Rev/RRE-dependent nuclear export and the DEAG-box mutant showed a dominant negative activity. Our data propose that HIV-1 utilizes the anti-viral factor MOV10 to function as a co-factor of Rev and demonstrate the complicated effects of MOV10 on HIV-1 life cycle. PMID- 26379092 TI - Widely Tunable Distributed Bragg Reflectors Integrated into Nanowire Waveguides. AB - Periodic structures with dimensions on the order of the wavelength of light can tailor and improve the performance of optical components, and they can enable the creation of devices with new functionalities. For example, distributed Bragg reflectors (DBRs), which are created by periodic modulations in a structure's dielectric medium, are essential in dielectric mirrors, vertical cavity surface emitting lasers, fiber Bragg gratings, and single-frequency laser diodes. This work introduces nanoscale DBRs integrated directly into gallium nitride (GaN) nanowire waveguides. Photonic band gaps that are tunable across the visible spectrum are demonstrated by precisely controlling the grating's parameters. Numerical simulations indicate that in-wire DBRs have significantly larger reflection coefficients in comparison with the nanowire's end facet. By comparing the measured spectra with the simulated spectra, the index of refraction of the GaN nanowire waveguides was extracted to facilitate the design of photonic coupling structures that are sensitive to phase-matching conditions. This work indicates the potential to design nanowire-based devices with improved performance for optical resonators and optical routing. PMID- 26379091 TI - Human Alpha-Defensin HNP1 Increases HIV Traversal of the Epithelial Barrier: A Potential Role in STI-Mediated Enhancement of HIV Transmission. AB - Alpha-defensins, including human neutrophil peptides 1-3 (HNP1-3) and human defensin 5 (HD5), are elevated at the genital mucosa in individuals with sexually transmitted infections (STIs). The presence of STIs is associated with an increased risk of human immunodeficiency virus (HIV) transmission, suggesting there may be a role for defensins in early events of HIV transmission. HD5 has been demonstrated to contribute to STI-mediated increased HIV infectivity in vitro. HNPs exhibit anti-HIV activity in vitro. However, increased levels of HNPs have been associated with enhanced HIV acquisition and higher viral load in breast milk. This study found that HNP1, but not HD5, significantly disrupted epithelial integrity and promoted HIV traversal of epithelial barriers. Linear HNP1 with the same charges did not affect epithelial permeability, indicating that the observed effect of HNP1 on the epithelial barrier was structure dependent. These results suggest a role for HNP1 in STI-mediated enhancement of HIV transmission. PMID- 26379093 TI - Locking Compression Plate Fixation of Equine Tarsal Subluxations. AB - OBJECTIVE: To report the clinical findings and outcome of locking compression plate (LCP) fixation of tarsal subluxations in horses. STUDY DESIGN: Retrospective case series. ANIMALS: Horses (n = 3) and ponies (2). METHODS: All horses and ponies diagnosed with tarsal subluxations and treated with LCP fixation at our institution between 2011 and 2013 were included. Data were collected from the medical records, including all radiographic and computed tomographic (CT) studies and reviewed. Long-term (>1 year) followup examination, including owner interview, and clinical and radiographic examinations were performed for all cases. RESULTS: Subluxations of the tarsometatarsal (n = 3) and proximal intertarsal (2) joints were diagnosed. CT examinations revealed complex joint injuries, including a combination of avulsion fragments and compression injuries at the opposite side of the joint from the subluxation. The LCP was applied to the plantarolateral or medial side of the limb. All horses survived and were discharged from the hospital. Short-term complications included mild laminitis (n = 1) and peroneus tertius rupture (2). At long-term followup, both ponies were sound and used as intended, whereas all horses showed mild to moderate lameness at the trot and were used for pleasure riding only. Radiographic signs of osteoarthritis developed in the joint affected by subluxation in all cases and in adjacent small tarsal joints in 2 horses and 1 pony. CONCLUSION: LCP fixation of tarsal subluxations resulted in stable fixation and allowed adequate healing. Subluxation of the small tarsal joints represents a complex injury and osteoarthritis commonly develops in the affected and adjacent joints. PMID- 26379094 TI - Elevated Accumulation of Parabens and their Metabolites in Marine Mammals from the United States Coastal Waters. AB - The widespread exposure of humans to parabens present in personal care products is well-known. Nevertheless, little is known about the accumulation of parabens in marine organisms. In this study, six parabens and four common metabolites of parabens were measured in 121 tissue samples from eight species of marine mammals collected along the coastal waters of Florida, California, Washington, and Alaska. Methyl paraben (MeP) was the predominant compound found in the majority of the marine mammal tissues analyzed, and the highest concentration found was 865 ng/g (wet weight [wet wt]) in the livers of bottlenose dolphins from Sarasota Bay, FL. 4-Hydroxybenzoic acid (4-HB) was the predominant paraben metabolite found in all tissue samples. The measured concentrations of 4-HB were on the order of hundreds to thousands of ng/g tissue, and these values are some of the highest ever reported in the literature. MeP and 4-HB concentrations showed a significant positive correlation (p < 0.05), which suggested a common source of exposure to these compounds in marine mammals. Trace concentrations of MeP and 4 HB were found in the livers of polar bears from the Chuckchi Sea and Beaufort Sea, which suggested widespread distribution of MeP and 4-HB in the oceanic environment. PMID- 26379096 TI - Revisiting the surface anatomy of the sciatic nerve in the gluteal region in children using computed tomography. AB - No anatomy text specifically describes the course of the sciatic nerve (SN) in the gluteal region in children. Anatomical information is largely derived from cadaveric studies of adults, so accurate anatomical information about the location of the SN in children is required. The aim of this study is to assess the surface anatomy of the SN in children using computed tomography (CT). After excluding studies with pelvic pathology, 75 CT scans were analyzed. Three groups were selected for analysis (0-2, 4-6, and 8-10 years). The position of the SN was measured between the posterior superior iliac spine (PSIS) and the ischial tuberosity (IT) and between the IT and the greater trochanter (GT) using 3 dimensional images. In the 0-2 age group, the SN crossed the middle third of a line between the PSIS and the IT in 94% and the GT and the IT in 80% of cases. In the 4-6 age group, the SN crossed the middle third of a line between the PSIS and the IT in 96% and the GT and the IT in 87%. In the 8-10 age group, the SN crossed the middle third of a line between the PSIS and the IT in 100% and the GT and the IT in 71%. The findings indicate that the SN in children is most accurately located in the middle third along a line drawn from the PSIS to the IT and the GT to the IT. Our study is the first to provide anatomical CT data from living children to guide interventions in the gluteal region. PMID- 26379095 TI - Home Use of an Artificial Beta Cell in Type 1 Diabetes. AB - BACKGROUND: The feasibility, safety, and efficacy of prolonged use of an artificial beta cell (closed-loop insulin-delivery system) in the home setting have not been established. METHODS: In two multicenter, crossover, randomized, controlled studies conducted under free-living home conditions, we compared closed-loop insulin delivery with sensor-augmented pump therapy in 58 patients with type 1 diabetes. The closed-loop system was used day and night by 33 adults and overnight by 25 children and adolescents. Participants used the closed-loop system for a 12-week period and sensor-augmented pump therapy (control) for a similar period. The primary end point was the proportion of time that the glucose level was between 70 mg and 180 mg per deciliter for adults and between 70 mg and 145 mg per deciliter for children and adolescents. RESULTS: Among adults, the proportion of time that the glucose level was in the target range was 11.0 percentage points (95% confidence interval [CI], 8.1 to 13.8) greater with the use of the closed-loop system day and night than with control therapy (P<0.001). The mean glucose level was lower during the closed-loop phase than during the control phase (difference, -11 mg per deciliter; 95% CI, -17 to -6; P<0.001), as were the area under the curve for the period when the glucose level was less than 63 mg per deciliter (39% lower; 95% CI, 24 to 51; P<0.001) and the mean glycated hemoglobin level (difference, -0.3%; 95% CI, -0.5 to -0.1; P=0.002). Among children and adolescents, the proportion of time with the nighttime glucose level in the target range was higher during the closed-loop phase than during the control phase (by 24.7 percentage points; 95% CI, 20.6 to 28.7; P<0.001), and the mean nighttime glucose level was lower (difference, -29 mg per deciliter; 95% CI, -39 to -20; P<0.001). The area under the curve for the period in which the day and-night glucose levels were less than 63 mg per deciliter was lower by 42% (95% CI, 4 to 65; P=0.03). Three severe hypoglycemic episodes occurred during the closed-loop phase when the closed-loop system was not in use. CONCLUSIONS: Among patients with type 1 diabetes, 12-week use of a closed-loop system, as compared with sensor-augmented pump therapy, improved glucose control, reduced hypoglycemia, and, in adults, resulted in a lower glycated hemoglobin level. (Funded by the JDRF and others; AP@home04 and APCam08 ClinicalTrials.gov numbers, NCT01961622 and NCT01778348.). PMID- 26379097 TI - Net clinical benefit of edoxaban versus no treatment in a 'real world' atrial fibrillation population: A modelling analysis based on a nationwide cohort study. AB - BACKGROUND: In non-valvular atrial fibrillation (AF), oral anticoagulation reduces the risk of thromboembolism such as stroke and systemic embolism (SSE), but increases the risk of major bleeding such as intracranial haemorrhage (ICH). The risk-benefit balance between SSE versus ICH can be expressed as the net clinical benefit (NCB); however, the risk of SSE and ICH varies according to clinical factors that can be assessed using CHADS2, CHA2DS2-VASc (both quantifying risk of stroke) and HAS-BLED (quantifying risk of major bleeding) scores, respectively. METHODS: Using established modelling based on event rates for thromboembolism and haemorrhage in the Danish nationwide cohort study, we tested the hypothesis that edoxaban has a superior NCB compared with warfarin. RESULTS: In our overall model, compared to no treatment, warfarin had a NCB of 0.26 (95% CI 0.24,0.28) events prevented per 100 patient years, edoxaban 60 mg daily a NCB of 0.71 [0.69,0.76], and edoxaban 30 mg daily a NCB of 0.71 [0.0.68,0.73]. When compared to no treatment, both doses of edoxaban have superior NCB values than those of warfarin at all CHADS2 and CHA2DS2-VASc scores. At CHADS2 >=2 and CHA2DS2-VASc >=2, edoxaban 60 mg dose had a better NCB than the 30 mg dose or warfarin, when compared to no treatment. With HAS-BLED score >=3, both doses of edoxaban had a positive NCB compared to warfarin, at CHADS2 or CHA2DS2-VASc >=2. CONCLUSION: Our modelling study suggests that both 30 mg and 60 mg doses of edoxaban have a favourable NCB compared to warfarin, and the degree of benefit differs according to CHADS2, CHA2DS2-VASc and HAS-BLED scores. At CHA2DS2-VASc score >=2, both edoxaban doses were superior to warfarin, but compared to no treatment, the 60 mg dose had a better NCB than the 30 mg dose or warfarin. PMID- 26379098 TI - The Juxtaposition of Population Science and Individual Treatment Recommendations for Intermittent Androgen Deprivation Therapy. PMID- 26379099 TI - Plasma anti-Mullerian hormone as a predictive endocrine marker to select Bos taurus (Holstein) and Bos indicus (Nelore) calves for in vitro embryo production. AB - This study evaluated the association between plasma anti-Mullerian hormone (AMH) concentrations and in vitro embryo production in Bos indicus (Nelore; experiment 1) and Bos taurus (Holstein; experiment 2) calves superstimulated or not with 140 mg of porcine follicle-stimulating hormone (pFSH; 4 decreasing doses twice daily). Oocytes were recovered from calves aged 2 to 4 mo after receiving gonadotropin stimulation (Nelore, n = 15; Holstein, n = 12) or not (Nelore, n = 15; Holstein, n = 12). Cycling heifers formed a positive control group (n = 15 for Nelore [aged 18-24 mo], n = 10 for Holstein [aged 14-16 mo]). All the calves underwent laparoscopic ovum pickup, and cycling heifers underwent a regular transvaginal ultrasound-guided ovum pickup for oocyte recovery. Immediately before oocyte retrieval, blood samples were taken for subsequent AMH determination (ng/mL). Regardless of the genetic group, calves that received pFSH (3.6 +/- 1.1 in Nelore and 4.6 +/- 1.2 in Holstein) or did not receive pFSH (3.2 +/- 1.0 in Nelore and 2.5 +/- 0.8 in Holstein) had greater plasma AMH concentrations (P = 0.01 in Nelore and P = 0.003 in Holstein) than cycling heifers (1.1 +/- 0.2 in Nelore and 0.6 +/- 0.07 in Holstein). AMH concentrations in calves with or without pFSH were similar in both genetic groups (3.6 +/- 1.1 vs 3.2 +/- 1.0 in Nelore; 4.6 +/- 1.2 vs 2.5 +/- 0.8 in Holstein). In calves, positive correlations were observed between plasma AMH concentrations and the numbers of follicles >2 mm (r = 0.86, P < 0.0001 in Nelore; r = 0.78, P < 0.0001 in Holstein), cumulus-oocyte complexes (COCs) retrieved (r = 0.91, P < 0.0001 in Nelore; r = 0.82, P < 0.0001 in Holstein), COCs cultured (r = 0.71, P < 0.0001 in Nelore; r = 0.79, P < 0.0001 in Holstein), and blastocysts produced (r = 0.62, P = 0.0003 in Nelore; r = 0.58, P = 0.009 in Holstein), and these results were independent of pFSH treatment. In conclusion, calves had greater plasma AMH concentrations than cycling heifers. In addition, treatment with pFSH did not influence AMH concentrations in calves, regardless of the genetic group. More importantly, plasma AMH concentrations were positively correlated with the antral follicle population and the number of COCs retrieved, COCs cultured, and blastocysts produced in B indicus and B taurus calves. Therefore, AMH is a promising tool for selecting oocyte donor calves to maximize results during in vitro embryo production. PMID- 26379100 TI - Studies on lysophosphatidic acid action during in vitro preimplantation embryo development. AB - Assisted reproductive technologies, including in vitro embryo production (IVP), have been successfully used in animal reproduction to optimize breeding strategies for improved production and health in animal husbandry. Despite the progress in IVP techniques over the years, further improvements in in vitro embryo culture systems are required for the enhancement of oocyte and embryo developmental competence. One of the most important issues associated with IVP procedures is the optimization of the in vitro culture of oocytes and embryos. Studies in different species of animals and in humans have identified important roles for receptor-mediated lysophosphatidic acid (LPA) signaling in multiple aspects of human and animal reproductive tract function. The data on LPA signaling in the ovary and uterus suggest that LPA can directly contribute to embryo-maternal interactions via its influence on early embryo development beginning from the influence of the ovarian environment on the oocyte to the influence of the uterine environment on the preimplantation embryo. This review discusses the current status of LPA as a potential supplement in oocyte maturation, fertilization, and embryo culture media and current views on the potential involvement of the LPA signaling pathway in early embryo development. PMID- 26379102 TI - Use of intravenous insulin aspart for treatment of naturally occurring diabetic ketoacidosis in dogs. AB - OBJECTIVES: To characterize the utility and safety of IV insulin aspart in the treatment of diabetes ketoacidosis (DKA) in dogs and to determine the times to resolution of hyperglycemia, ketonemia, and acidemia in dogs treated with IV insulin aspart. DESIGN: Prospective noncontrolled single arm study of dogs with DKA between February 2010 and March 2011. SETTING: University teaching hospital. ANIMALS: Six dogs with spontaneous DKA and blood glucose (BG) concentration >13.8 mmol/L (250 mg/dL), pH between 7.0 and 7.35, and blood beta-hydroxybutyrate >2.0 mmol/L were treated with an IV continuous rate infusion (CRI) of aspart insulin. The time to biochemical resolution of DKA was defined as the time interval from when the IV CRI of aspart insulin began until marked hyperglycemia (BG concentration >13.8 mmol/L [250 mg/dL]), acidemia (venous pH <7.35), and ketonemia (beta-hydroxybutyrate concentration >2.0 mmol/L) resolved. Aspart insulin was administered as an IV CRI at an initial dose of 0.09 U/kg/h. The dose was adjusted according to a previously published protocol. MEASUREMENTS AND MAIN RESULTS: The median time to biochemical resolution of DKA in dogs treated with insulin aspart was 28 hours (range, 20-116 h). Mean BG concentration decreased significantly from the time IV fluid resuscitation began (32.0 mmol/L [576 mg/dL]; range, 14.9-38.9 mmol/L [268-700 mg/dL]) until 6 hours later when IV aspart insulin CRI began (20.1 mmol/L [363 mg/dL]; range, 9.4-26.1 mmol/L [169 470 mg/dL], P = 0.03). No adverse effects were observed in association with IV insulin aspart administration. Median cost of hospitalization was US$3,477 (range, US$1,483-10,469). Median total units per kilogram of administered IV insulin aspart was 2.97 U/kg (range, 2.04-10.52 U/kg). CONCLUSIONS: Intravenous CRI of insulin aspart is a safe and effective treatment for DKA in dogs. IV fluid resuscitation is recommended prior to insulin administration. PMID- 26379103 TI - Content Analysis of Select YouTube Postings: Comparisons of Reactions to the Sandy Hook and Aurora Shootings and Hurricane Sandy. AB - This study details an innovative and methodical content analysis of 2,207 YouTube comments from four different YouTube videos (e.g., breaking news or memorials) related to the 2012 Sandy Hook Elementary School and Aurora theater mass shootings and the catastrophic Hurricane Sandy. As expected, YouTube comments associated with the Sandy Hook shootings (particularly those from a memorial video) were especially likely to feature compassion and grief with lessened hostility. This study highlights differing online contexts by which individuals show grief and related emotions following man-made and natural calamities and how even in an online environment-powerful situational contexts greatly guide behavior. PMID- 26379101 TI - Evidence for chromosome fragility at the frataxin locus in Friedreich ataxia. AB - Friedreich ataxia (FRDA) is a member of the Repeat Expansion Diseases, a group of genetic conditions resulting from an increase/expansion in the size of a specific tandem array. FRDA results from expansion of a GAA/TTC-tract in the first intron of the frataxin gene (FXN). The disease-associated tandem repeats all form secondary structures that are thought to contribute to the propensity of the repeat to expand. The subset of these diseases that result from a CGG/CCG-repeat expansion, such as Fragile X syndrome, also express a folate-sensitive fragile site coincident with the repeat on the affected chromosome. This chromosome fragility involves the generation of chromosome/chromatid gaps or breaks, or the high frequency loss of one or both copies of the affected gene when cells are grown under folate stress or as we showed previously, in the presence of an inhibitor of the ATM checkpoint kinase. Whether Repeat Expansion Disease loci containing different repeats form similar fragile sites was not known. We show here that the region of chromosome 9 that contains the FXN locus is intrinsically prone to breakage in vivo even in control cells. However, like FXS alleles, FRDA alleles show significantly elevated levels of chromosome abnormalities in the presence of an ATM inhibitor, consistent with the formation of a fragile site. PMID- 26379104 TI - Reopening of a Full-Thickness Macular Hole 2 Years After Pharmacologic Closure With Ocriplasmin. PMID- 26379105 TI - Telomerase: a target for colorectal cancer treatment? PMID- 26379106 TI - Different rates of defense evolution and niche preferences in clonal and nonclonal milkweeds (Asclepias spp.). AB - Given the dual role of many plant traits to tolerate both herbivore attack and abiotic stress, the climatic niche of a species should be integrated into the study of plant defense strategies. Here we investigate the impact of plant reproductive strategy and components of species' climatic niche on the rate of chemical defense evolution in the milkweeds using a common garden experiment of 49 species. We found that across Asclepias species, clonal reproduction repeatedly evolved in lower temperature conditions, in species generally producing low concentrations of a toxic defense (cardenolides). Additionally, we found that rates of cardenolide evolution were lower for clonal than for nonclonal species. We thus conclude that because the clonal strategy is based on survival, long generation times, and is associated with tolerance of herbivory, it may be an alternative to toxicity in colder ecosystems. Taken together, these results indicate that the rate of chemical defense evolution is influenced by the intersection of life-history strategy and climatic niches into which plants radiate. PMID- 26379107 TI - Multidrug Efflux Pumps Attenuate the Effect of MGMT Inhibitors. AB - Various mechanisms of drug resistance attenuate the effectiveness of cancer therapeutics, including drug transport and DNA repair. The DNA repair protein O(6)-methylguanine-DNA methyltransferase (MGMT) is a key factor determining the resistance against alkylating anticancer drugs inducing the genotoxic DNA lesions O(6)-methylguanine and O(6)-chloroethylguanine, and MGMT inactivation or depletion renders cells more susceptible to treatment with methylating and chloroethylating agents. Highly specific and efficient inhibitors of the repair protein MGMT were designed, including O(6)-benzylguanine (O(6)BG) and O(6)-(4 bromothenyl)guanine (O(6)BTG) that are nontoxic on their own. Unfortunately, these inhibitors do not select between MGMT in normal and cancer cells, causing nontarget effects in the healthy tissue. Therefore, a targeting strategy for MGMT inhibitors is required. Here, we used O(6)BG and O(6)BTG conjugated to beta-d glucose (O(6)BG-Glu and O(6)BTG-Glu, respectively) in order to selectively inhibit MGMT in tumors, harnessing their high demand for glucose. Both glucose conjugates efficiently inhibited MGMT in several cancer cell lines, but with different extents of sensitization to DNA alkylating agents, with lomustine being more effective than temozolomide. We further show that the glucose conjugates are subject to ATP-binding cassette (ABC) transporter mediated efflux, involving P glycoprotein, MRP1, and BCRP, which impacts the efficiency of MGMT inhibition. Surprisingly, also O(6)BG and O(6)BTG were subject to an active transport out of the cell. We also show that pharmacological inhibition of efflux transporters increases the induction of cell death following treatment with these MGMT inhibitors and temozolomide. We conclude that strategies of attenuating the efflux by ABC transporters are required for achieving successful MGMT targeting. PMID- 26379108 TI - Skeletally Diverse Synthesis of Innovative [2,1-c]-1,4-Oxazepine and [1,4] Quinoxaline Systems. AB - An efficient, innovative synthesis of [2,1-c]-1, 4-oxazepine and [1,4] quinoxaline heterocycles along with the embodied pyrimido-pyrrolo motifs was established. Initially, the pyrrole ring was installed using microwave irradiation through an intramolecular base-catalyzed cyclization between acetyl bromomethyl pyrimidine dione and o-amino phenyl methanol or o-phenylenediamine methyl benzoates. Furthermore, oxazepine, and quinoxaline scaffolds were constructed by an acid-catalyzed condensation with a variety of aldehydes by an unconventional Pictet-Spengler reaction strategy. An important aspect of this work is to build novel heterocyclic ring systems with potential medicinal interest. PMID- 26379109 TI - Development and validation of a UHPLC-MS/MS bioanalytical method to quantify in plasma the analgesic candidate PT-31 following a preliminary pharmacokinetic study in rats. AB - A selective and sensitive UHPLC-MS/MS bioanalytical method to determine PT-31, an analgesic drug candidate, in rat plasma was developed and validated. Analyses were performed using a UHPLC-MS/MS system equipped with an electrospray ionization interface operating in the positive ionization mode using a C18 reversed-phase column with a mobile phase of water:acetonitrile (68:31, v/v) containing 0.1% acetic acid eluting in a gradient mode with a flow rate of 0.3 mL/min. Plasma samples were deproteinized with cold acetonitrile containing 0.01% TFA (1:2, v/v) and 50 MUL of the supernatant were injected into the system. PT-31 and phenytoin (internal standard) retention times were roughly 1.0 and 1.5 min, respectively. Linear standard curves were plotted for the 0.01-10 ug/mL concentration range, with a coefficient of determination > 0.99. The method's precision was over 88%. Maximum intra- and inter-day relative standard deviations were 14.6% and 11.6%, respectively. Interfering substances were not detected in the chromatogram, indicating that the method was specific. PT-31 stability was assessed under different temperature and storage settings. The method was used to characterize PT-31 plasma pharmacokinetics following administration of 5 mg/kg i.v. to Wistar rats. Therefore, the method described is sensitive, linear, precise and specific enough to determine PT-31 in preclinical pharmacokinetic investigations. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26379112 TI - Incorrect CME Quiz. PMID- 26379113 TI - Star-Shaped Polypeptides: Synthesis and Opportunities for Delivery of Therapeutics. AB - Significant advances in the synthesis of polypeptides by N-carboxyanhydride (NCA) polymerisation over the last decade have enabled the design of advanced polypeptide architectures such as star-shaped polypeptides. These materials combine the functionality offered by amino acids with the flexibility of creating stable nanoparticles with adjustable cargo space for therapeutic delivery. This review highlights recent advances in the synthesis of star polypeptides by NCA polymerisation followed by a critical review of the applications of this class of polymer in the delivery of therapeutic agents. This includes examples of traditional small-molecule drugs as well as the emerging class of biologics such as genetic therapeutics (gene delivery). PMID- 26379114 TI - Cone beam computed tomography evaluation of distance from cementoenamel junction to alveolar crest before and after nonextraction orthodontic treatment. AB - OBJECTIVE: To evaluate the distance between the cementoenamel junction and the alveolar bone crest before and after orthodontic treatment using cone beam computed tomography (CBCT). MATERIALS AND METHODS: The sample comprised 30 patients with Angle Class I malocclusion and mild to moderate crowding. The study database comprised dental CBCT scans obtained before and after orthodontic treatment. The distance between the cementoenamel junction to the bone crest of the buccal (n = 720) and lingual (n = 720) surfaces was measured in 24 teeth for each patient using a specific software tool (Xoran version 3.1.62). The Wilcoxon test was used for statistical analysis, and the level of significance was set at P < .05. RESULTS: The distance between the cementoenamel junction and the bone crest increased in 822 (57%) of the 1440 surfaces after orthodontic treatment. The buccal surface of the lower central incisors had the greatest frequency of increased distance (75%), and the lingual surface of lateral incisors had the lowest (40%). The distance between the cementoenamel junction and the alveolar bone crest was greater than 2 mm (alveolar bone dehiscence) in 162 (11%) of the 1440 surfaces before orthodontic treatment and in 279 (19%) after treatment. CONCLUSIONS: The distance from the cementoenamel junction to the bone crest changed after orthodontic treatment; the distance was greater than 2 mm in 11% of the surfaces before treatment and in 19% after treatment. PMID- 26379115 TI - The Frequency and Prognostic Impact of Pathological Microscopic Vascular Invasion According to Tumor Size in Non-Small Cell Lung Cancer. AB - BACKGROUND: Microscopic vascular invasion (MVI) in patients with non-small cell lung cancer (NSCLC) has been reported to be a strong predictor of poor outcomes but it has not been a descriptor of the TNM classification. The purposes of this study were to determine whether the presence of MVI is related to a predictor of poor outcomes and to explore the degree of MVI according to tumor size. METHODS: A total of 1,884 patients with stage pT1-4N0-2 NSCLC who underwent complete resection comprised the study sample. Overall survival (OS) and recurrence-free proportion were estimated using the Kaplan-Meier method. The Cox proportional hazards model was used to assess independent predictors of poor outcomes. RESULTS: Of 1,884 patients, 1,097 (58.2%) had MVI. Multivariate analysis showed MVI was a significant independent predictor of unfavorable OS (hazard ratio, 1.666; P < .001) and recurrence (hazard ratio, 2.268; P < .001). The frequency of MVI varied according to tumor size, and in each cohort of tumor sizes <= 2 cm, > 2 to 3 cm, and > 3 to 5 cm, there were significant differences in survival outcome by MVI status. The proportions of patients with a 5-year recurrence-free period with tumor sizes <= 2 cm, > 2 to 3 cm, and > 3 to 5 cm between MVI (+) and MVI (-) were 93.0% and 72.5% (P < .001), 90.8% and 63.3% (P < .001), and 86.4% and 59.9% (P < .001), respectively. CONCLUSIONS: This study demonstrated that MVI was a strong predictor of poor outcomes and that the effect is more prominent in patients with tumor sizes <= 5 cm. Further analysis of survival and MVI should be collected for future revision of the TNM system. PMID- 26379116 TI - Insights into the nature of uranium target proteins within zebrafish gills after chronic and acute waterborne exposures. AB - New data on the nature of the protein targets of uranium (U) within zebrafish gills were collected after waterborne exposure, with the aim of a better understanding of U toxicity mechanisms. Some common characteristics of the U protein target binding properties were found, such as their role in the regulation of other essential metals and their phosphorus content. In total, 21 potential protein targets, including hemoglobin, are identified and discussed in terms of the literature. PMID- 26379117 TI - Quantifying Changes in Nasal Tip Support. AB - IMPORTANCE: Imparting surgical change to the nasal tip remains one of the most challenging aspects of rhinoplasty. The surgeon must assess the tip preoperatively and execute the necessary maneuvers to impart the desired change. OBJECTIVE: To assess nasal tip resistance to compression in a cadaveric model before and after specific rhinoplasty maneuvers using a novel method. DESIGN, SETTING, AND MATERIALS: Open rhinoplasty maneuvers were performed at an academic tertiary care center on 6 fresh-thawed cadaver heads. Assessment of tip support was performed with a motorized, computer-controlled test stand equipped with a digital load cell. Tip support was assessed by compression to a depth of 2.5 mm from contact both preoperatively and after each surgical maneuver. All force data were recorded in pound-force and converted to newtons (N) following analysis. MAIN OUTCOMES AND MEASURES: Nasal tip support, measured as resistance to compression, before and after various rhinoplasty maneuvers. RESULTS: Following the elevation of the skin-soft-tissue envelope with septoplasty, resistance to compression (1.82 N) was not significantly different from the preoperative assessment (1.60 N for all specimens). Tip support following placement of a caudal extension graft was significantly different from all other conditions (3.16 N; P < .01), showing support increased by more than 66% from preoperative assessment. Placement of columellar strut (1.28 N) did not show significant increase in tip support. Tip support was decreased slightly after placement of intradomal sutures, which was significant (1.22 N; P < .01). CONCLUSIONS AND RELEVANCE: This study demonstrates the use of materials testing equipment to assess and quantify change in tip support after several rhinoplasty maneuvers. Minor supporting maneuvers that rely on healing and scar do not significantly alter tip support in a cadaveric model. Caudal extension graft is an important maneuver imparting significant effect on nasal tip support. LEVEL OF EVIDENCE: NA. PMID- 26379119 TI - Gold Nanocluster-Assisted Fluorescent Detection for Hydrogen Peroxide and Cholesterol Based on the Inner Filter Effect of Gold Nanoparticles. AB - We developed a simple, sensitive inner filter effect (IFE)-based fluorescent assay for sensing H2O2 and cholesterol. In the process, poly(vinylpyrrolidone) protected gold nanoparticles (PVP-AuNPs) and fluorescent BSA-protected gold nanoclusters (BSA-AuNCs) were used as an IFE absorber/fluorophore pair. PVP-AuNPs can be a powerful absorber to influence the emission of the fluorophore, BSA AuNCs, in the IFE-based fluorescent assays. That is due to the high extinction coefficient of AuNPs and the complementary overlap between the surface plasmon resonance (SPR) absorption of PVP-AuNPs and the excitation of BSA-AuNCs. The PVP Au seeds, produced by directly mixing PVP with HAuCl4, were able to catalyze H2O2 to enlarge AuNPs. The SPR absorption of PVP-AuNPs was enhanced with an increased concentration of H2O2 and, subsequently, induced significant fluorescence quenching of BSA-AuNCs. The IFE-based fluorescent assay enabled the detection of H2O2 and generation of H2O2 in the presence of O2/cholesterol and cholesterol oxidase (ChOx) by the fluorescence response of BSA-AuNCs. The present IFE-based approach can detect H2O2 ranging from 1 to 100 MUM with a detection limit of 0.8 MUM and cholesterol ranging from 1 to 100 MUM with a detection limit of 1.4 MUM. PMID- 26379118 TI - Organ-specific efficacy of HSP90 inhibitor in multiple-organ metastasis model of chemorefractory small cell lung cancer. AB - Small-cell lung cancer (SCLC) accounts for nearly 15% of lung cancer cases and exhibits aggressive clinical behavior characterized by rapid growth and metastatic spread to multiple organs. About 70% of patients with SCLC present with extensive disease and distant metastases at diagnosis. HSP90 is a 90-kDa molecular chaperone whose association is required for the stability and function of its numerous "client proteins." Here, we assessed the therapeutic potential of the HSP90 inhibitor 17-DMAG in SCLC. Notably, 17-DMAG hindered the viability of human SCLC cell lines-regardless of their chemosensitivity-via the decreased expression of client proteins, including the proto-oncogene c-Raf (also known as RAF1). In an in vivo imaging model of SCLC multiple-organ metastasis with the human SCLC cell line SBC-5, treatment with 17-DMAG remarkably inhibited the formation of metastatic sites in the liver, but was ineffective in hindering the progression of bone lesions. The latter was likely the result of activation of osteoclasts. IGF-1, which is supposed to be rich in bone environment, preserved c Raf expression and maintained viability of SBC-5 cells treated with 17-DMAG. Furthermore, the combined use of a bisphosphonate with 17-DMAG significantly attenuated the progression of metastases in both the liver and the bone. These findings suggest that therapeutic effects of HSP90 inhibitors may be organ specific and should be carefully monitored in SCLC clinical trials. PMID- 26379120 TI - A monoclonal antibody to an abrin chimera recognizing a unique epitope on abrin A chain confers protection from abrin-induced lethality. AB - Abrin, obtained from the seeds of Abrus precatorius plant, is a potent toxin belonging to the family of type II ribosome-inactivating proteins. Recently, a recombinant vaccine consisting of the A subunits of abrin and its homolog Abrus precatorius agglutinin (APA) was demonstrated to protect mice from abrin lethality. Toward identifying neutralizing epitopes recognized during this response, we generated monoclonal antibodies against the proposed vaccine candidate. One antibody, namely A7C4, the corresponding epitope of which was found to be distal to the active site of the enzymatic A chain, prevented abrin mediated toxicity on cells and abrin-induced lethality in mice but did not inhibit the catalytic activity of the A chain. The in vivo protection conferred by monoclonal antibody A7C4 highlights the potential use of this antibody as a promising immunotherapeutic. PMID- 26379123 TI - Nucleophilic Aromatic Substitution (SNAr) as an Approach to Challenging Carbohydrate-Aryl Ethers. AB - A general and practical route to carbohydrate-aryl ethers by nucleophilic aromatic substitution (SNAr) is reported. Upon treatment with KHMDS, C-O bond formation occurs between carbohydrate alcohols and a diverse range of fluorinated (hetero)aromatics to provide the targets in good to excellent yields. Commercially available arylating agents, high atom economy, and high regioselectivity are notable features of the protocol. The aryl ether products have potential for wide-ranging applications as exemplified by the synthesis of a novel chiral P,N-ligand. PMID- 26379121 TI - Understanding patient participation behaviour in studies of COPD support programmes such as pulmonary rehabilitation and self-management: a qualitative synthesis with application of theory. AB - BACKGROUND: In chronic obstructive pulmonary disease (COPD), the problem of poor patient participation in studies of self-management (SM) and pulmonary rehabilitation (PR) programmes (together referred to as COPD support programmes) is established. Understanding this problem beyond the previously reported socio demographics and clinical factors is critical. AIMS: The aim of this study was to explore factors that explain patient participation in studies of COPD support programmes. METHODS: Thematic 'framework' synthesis was conducted on literature published from 1984 to 1 February 2015. Emergent themes and subthemes were mapped onto the adapted 'attitude-social influence-external barriers' and the 'self regulation' models to produce analytical themes. RESULTS: Ten out of 12 studies were included: PR (n=9) and SM (n=1). Three descriptive themes with 38 subthemes were mapped onto the models' constructs, and it generated four analytical themes: 'attitude', 'social influences' and 'illness' and 'intervention representations'. The following factors influenced (1) attendance-helping oneself through health improvements, perceived control of worsening condition, perceived benefits and positive past experience of the programme, as well as perceived positive influence of professionals; (2) non-attendance-perceived negative effects and negative past experience of the programme, perceived physical/practical concerns related to attendance, perceived severity of condition/symptoms and perceived negative influence of professionals/friends; (3) dropout-no health improvements perceived after attending a few sessions of the programme, perceived severity of the condition and perceived physical/practical concerns related to attendance. CONCLUSIONS: Psychosocial factors including perceived practical/physical concerns related to attendance influenced patients' participation in COPD support programmes. Addressing the negative beliefs/perceptions via behaviour change interventions may help improve participation in COPD support programmes and, ultimately, patient outcomes. PMID- 26379122 TI - The effectiveness and cost-effectiveness of mindfulness-based cognitive therapy compared with maintenance antidepressant treatment in the prevention of depressive relapse/recurrence: results of a randomised controlled trial (the PREVENT study). AB - BACKGROUND: Individuals with a history of recurrent depression have a high risk of repeated depressive relapse/recurrence. Maintenance antidepressant medication (m-ADM) for at least 2 years is the current recommended treatment, but many individuals are interested in alternatives to m-ADM. Mindfulness-based cognitive therapy (MBCT) has been shown to reduce the risk of relapse/recurrence compared with usual care but has not yet been compared with m-ADM in a definitive trial. OBJECTIVES: To establish whether MBCT with support to taper and/or discontinue antidepressant medication (MBCT-TS) is superior to and more cost-effective than an approach of m-ADM in a primary care setting for patients with a history of recurrent depression followed up over a 2-year period in terms of preventing depressive relapse/recurrence. Secondary aims examined MBCT's acceptability and mechanism of action. DESIGN: Single-blind, parallel, individual randomised controlled trial. SETTING: UK general practices. PARTICIPANTS: Adult patients with a diagnosis of recurrent depression and who were taking m-ADM. INTERVENTIONS: Participants were randomised to MBCT-TS or m-ADM with stratification by centre and symptomatic status. Outcome data were collected blind to treatment allocation and the primary analysis was based on the principle of intention to treat. Process studies using quantitative and qualitative methods examined MBCT's acceptability and mechanism of action. MAIN OUTCOMES MEASURES: The primary outcome measure was time to relapse/recurrence of depression. At each follow-up the following secondary outcomes were recorded: number of depression free days, residual depressive symptoms, quality of life, health-related quality of life and psychiatric and medical comorbidities. RESULTS: In total, 212 patients were randomised to MBCT-TS and 212 to m-ADM. The primary analysis did not find any evidence that MBCT-TS was superior to m-ADM in terms of the primary outcome of time to depressive relapse/recurrence over 24 months [hazard ratio (HR) 0.89, 95% confidence interval (CI) 0.67 to 1.18] or for any of the secondary outcomes. Cost-effectiveness analysis did not support the hypothesis that MBCT-TS is more cost-effective than m-ADM in terms of either relapse/recurrence or quality-adjusted life-years. In planned subgroup analyses, a significant interaction was found between treatment group and reported childhood abuse (HR 1.89, 95% CI 1.06 to 3.38), with delayed time to relapse/recurrence for MBCT-TS participants with a more abusive childhood compared with those with a less abusive history. Although changes in mindfulness were specific to MBCT (and not m ADM), they did not predict outcome in terms of relapse/recurrence at 24 months. In terms of acceptability, the qualitative analyses suggest that many people have views about (dis)/continuing their ADM, which can serve as a facilitator or a barrier to taking part in a trial that requires either continuation for 2 years or discontinuation. CONCLUSIONS: There is no support for the hypothesis that MBCT TS is superior to m-ADM in preventing depressive relapse/recurrence among individuals at risk for depressive relapse/recurrence. Both treatments appear to confer protection against relapse/recurrence. There is an indication that MBCT may be most indicated for individuals at greatest risk of relapse/recurrence. It is important to characterise those most at risk and carefully establish if and why MBCT may be most indicated for this group. TRIAL REGISTRATION: Current Controlled Trials ISRCTN26666654. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and the National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care South West Peninsula and will be published in full in Health Technology Assessment; Vol. 19, No. 73. See the NIHR Journals Library website for further project information. PMID- 26379124 TI - Predictors of global functioning and employment 10 years following traumatic brain injury compared with orthopaedic injury. AB - OBJECTIVE: The aim of this study was to prospectively investigate predictors of global functioning and employment 10 years following traumatic brain injury (TBI) compared with orthopaedic trauma. RESEARCH DESIGN: Prospective cohort. METHODS: Ninety-seven individuals with complicated mild-to-severe TBI and 91 with traumatic orthopaedic injury were followed-up at 10 years post-injury. Global functioning (GOS-E) and employment status were recorded. RESULTS: Groups did not differ on global functioning or employment status. Post-TBI, shorter PTA and less severe orthopaedic injuries were associated with better global functioning; and shorter PTA and younger age were associated with employment. Following traumatic orthopaedic injury, younger age was associated with employment, but not after excluding individuals no longer in the labour force. CONCLUSIONS: In this sample, demographic factors and injury severity contribute to long-term outcomes following TBI, but not orthopaedic trauma. PTA continues to influence outcomes 10 years following TBI. There is ongoing detrimental influence of orthopaedic injuries on global functioning for individuals with TBI, suggesting a potential benefit in greater clinical attention to these injuries. Further understanding of the complex interplay between these predictors and other personal and environmental factors will contribute to improving individualized rehabilitation. PMID- 26379125 TI - Regulation of GacA in Pseudomonas chlororaphis Strains Shows a Niche Specificity. AB - The GacS/GacA two-component system plays a central role in the regulation of a broad range of biological functions in many bacteria. In the biocontrol organism Pseudomonas chlororaphis, the Gac system has been shown to positively control quorum sensing, biofilm formation, and phenazine production, but has an overall negative impact on motility. These studies have been performed with strains originated from the rhizosphere predominantly. To investigate the level of conservation between the GacA regulation of biocontrol-related traits in P. chlororaphis isolates from different habitats, the studies presented here focused on the endophytic isolate G5 of P. chlororaphis subsp. aurantiaca. A gacA mutant deficient in the production of N-acylhomoserine lactones (AHLs) and phenazine was isolated through transposon mutagenesis. Further phenotypic characterization revealed that in strain G5, similar to other P. chlororaphis strains, a gacA mutation caused inability to produce biocontrol factors such as phenazine, HCN and proteases responsible for antifungal activity, but overproduced siderophores. LC-MS/MS analysis revealed that AHL production was also practically abolished in this mutant. However, the wild type exhibited an extremely diverse AHL pattern which has never been identified in P. chlororaphis. In contrast to other isolates of this organism, GacA in strain G5 was shown to negatively regulate biofilm formation and oxidative stress response whilst positively regulating cell motility and biosynthesis of indole-3-acetic acid (IAA). To gain a better understanding of the overall impact of GacA in G5, a comparative proteomic analysis was performed revealing that, in addition to some of the traits like phenazine mentioned above, GacA also negatively regulated lipopolysaccharide (LPS) and trehalose biosynthesis whilst having a positive impact on energy metabolism, an effect not previously described in P. chlororaphis. Consequently, GacA regulation shows a differential strain dependency which is likely to be in line with their niche of origin. PMID- 26379126 TI - Pregnancy-Induced Hypertensive Disorders before and after a National Economic Collapse: A Population Based Cohort Study. AB - BACKGROUND: Data on the potential influence of macroeconomic recessions on maternal diseases during pregnancy are scarce. We aimed to assess potential change in prevalence of pregnancy-induced hypertensive disorders (preeclampsia and gestational hypertension) during the first years of the major national economic recession in Iceland, which started abruptly in October 2008. METHODS AND FINDINGS: Women whose pregnancies resulted in live singleton births in Iceland in 2005-2012 constituted the study population (N = 35,211). Data on pregnancy-induced hypertensive disorders were obtained from the Icelandic Medical Birth Register and use of antihypertensive drugs during pregnancy, including beta blockers and calcium channel blockers, from the Icelandic Medicines Register. With the pre-collapse period as reference, we used logistic regression analysis to assess change in pregnancy-induced hypertensive disorders and use of antihypertensives during the first four years after the economic collapse, adjusting for demographic and pregnancy characteristics, taking aggregate economic indicators into account. Compared with the pre-collapse period, we observed an increased prevalence of gestational hypertension in the first year following the economic collapse (2.4% vs. 3.9%; adjusted odds ratio [aOR] 1.47; 95 percent confidence interval [95%CI] 1.13-1.91) but not in the subsequent years. The association disappeared completely when we adjusted for aggregate unemployment rate (aOR 1.04; 95% CI 0.74-1.47). Similarly, there was an increase in prescription fills of beta-blockers in the first year following the collapse (1.9% vs.3.1%; aOR 1.43; 95% CI 1.07-1.90), which disappeared after adjusting for aggregate unemployment rate (aOR 1.05; 95% CI 0.72-1.54). No changes were observed for preeclampsia or use of calcium channel blockers between the pre- and post-collapse periods. CONCLUSIONS: Our data suggest a transient increased risk of gestational hypertension and use of beta-blockers among pregnant women in Iceland in the first and most severe year of the national economic recession. PMID- 26379127 TI - Effect of Tracheostomy on Weaning Parameters in Difficult-to-Wean Mechanically Ventilated Patients: A Prospective Observational Study. AB - BACKGROUND AND OBJECTIVE: Weaning parameters are commonly measured through an endotracheal tube in mechanically ventilated patients recovering from acute respiratory failure, however this practice has rarely been evaluated in tracheostomized patients. This study aimed to investigate changes in weaning parameters measured before and after tracheostomy, and to explore whether the data measured after tracheostomy were associated with weaning outcomes in difficult-to-wean patients. METHODS: In a two-year study period, we enrolled orotracheally intubated patients who were prepared for tracheostomy due to difficult weaning. Weaning parameters were measured before and after the conversion to tracheostomy and compared, and the post-tracheostomy data were tested for associations with weaning outcomes. RESULTS: A total of 86 patients were included. After tracheostomy, maximum inspiratory pressure (mean difference (Delta) = 4.4, 95% CI, 2.7 to 6.1, P<0.001), maximum expiratory pressure (Delta = 5.4, 95% CI, 2.9 to 8.0, P<0.001) and tidal volume (Delta = 33.7, 95% CI, 9.0 to 58.5, P<0.008) significantly increased, and rapid shallow breathing index (Delta = -14.6, 95% CI, -25.4 to -3.7, P<0.009) and airway resistance (Delta = -4.9, 95% CI, -5.8 to -4.0, P<0.001) significantly decreased. The patients who were successfully weaned within 90 days of the initiation of mechanical ventilation had greater increments in maximum inspiratory pressure (5.9 vs. 2.4, P = 0.04) and maximum expiratory pressure (8.0 vs. 2.0, P = 0.02) after tracheostomy than those who were unsuccessfully weaned. CONCLUSIONS: In conclusion, the conversion from endotracheal tube to tracheostomy significantly improved the measured values of weaning parameters in difficult-to-wean patients who subsequently weaned successfully from the mechanical ventilator. The change was significant only for airway resistance in patients who failed weaning. TRIAL REGISTRATION: ClinicalTrials.gov NCT01312142. PMID- 26379130 TI - Street Level Prostitution: A Systematic Literature Review. AB - The aim of this study was to synthesize research on female street level prostitutes for application in mental health practice and identification of future research needs. The data were from reports conducted in Westernized countries on female street level prostitutes between the years 2000 and 2014. Street level prostitutes are at high risk for HIV/STIs, chronic and acute physical/mental health problems, and violence, but there is a paucity of research on resilience and coping skills. We conclude that street level prostitutes suffer severe health disparities, yet they do not seek health care on a consistent basis. It is important for mental healthcare providers to offer women a safe, non judgmental environment while providing assessment and referral. Future research on mental health consequences as well as resilience and coping skills would support effective interventions that address the women holistically. PMID- 26379131 TI - A Conceptual Model for Nurses' Decision-making with the Aggressive Psychiatric Patient. AB - Violence in the acute care psychiatric setting is an ongoing serious problem. Maintenance of a safe therapeutic environment is a paramount responsibility of nurses practicing in this area. Ethical and legal standards demand that the nurse intervenes in aggressive situations in a manner that employs the least intrusive and restrictive measures necessary to provide safety. Therefore, accurate and effective decision-making in aggressive situations, which can escalate rapidly, is of great importance. This paper discusses a theoretical model for decision making in selecting interventions with aggressive psychiatric patients. This model may provide a basis for the development of training and education programs for effective decision-making in this area. PMID- 26379128 TI - Viral Restriction Activity of Feline BST2 Is Independent of Its N-Glycosylation and Induction of NF-kappaB Activation. AB - BST2 (CD317, tetherin, HM1.24) is an interferon-inducible transmembrane protein which can directly inhibit the release of enveloped virus particles from infected cells, and its anti-viral activity is reported to be related to the specific topological arrangement of its four structural domains. The N-terminal cytoplasmic tail of feline BST2 (fBST2) is characterized by a shorter N-terminal region compared to those of other known homologs. In this study, we investigated the functional impact of modifying the cytoplasmic tail region of fBST2 and its molecular mechanism. The fBST2 protein with the addition of a peptide at the N terminus retained anti-release activity against human immunodeficiency virus type 1 and pseudovirus based on feline immunodeficiency virus at a weaker level compared with the wild-type fBST2. However, the fBST2 protein with addition of a peptide internally in the ectodomain proximal to the GPI anchor still retained its anti-viral activity well. Notably, the N-glycosylation state and the cell surface level of the N-terminally modified variants were unlike those of the wild type protein, while no difference was observed in their intracellular localizations. However, in contrast to human BST2, the wild-type fBST2 did not show the ability to activate NF-kappaB. Consistent with previous reports, our findings showed that adding a peptide in the cytoplasmic tail region of fBST2 may influence its anti-viral activity. The shorter N-terminal cytoplasmic region of fBST2 compared with human BST2 did not apparently affect its anti-viral activity, which is independent of its N-glycosylation and ability to activate NF-kappaB. PMID- 26379132 TI - 'Responsible, but Still not a Real Treatment Partner': A Qualitative Study of the Experiences of Relatives of Patients on Outpatient Commitment Orders. AB - The aim of this study was to explore relatives' experiences when their family member is under an outpatient commitment order. A descriptive and exploratory approach was used based on qualitative interviews with 11 relatives. The relatives felt they had responsibility for the patient, but experienced a lack of recognition for their contribution to the treatment. Relatives paid little attention to coercion, but were more concerned about whether the follow-up care improved the patient's social functioning. They further reported an unmet need for information and guidance from healthcare staff to improve cooperation in the patient's care and treatment. PMID- 26379133 TI - Feasibility of Mindfulness-based Stress Reduction Intervention for Parents of Children with Developmental Delays. AB - Mindfulness-based stress reduction (MBSR) interventions are popular as a treatment strategy for myriad diagnoses in various settings, and may be beneficial for parents of children with developmental delays (DD). However, prior research suggests extreme levels of stress and extraordinary demands on time among these parents, making the feasibility of effectively implementing MBSR with this population questionable. This study examined the feasibility of administering standard MBSR to a diverse community-based sample of parents of young children with DD. The potential impact of MBSR interventions includes improvement in parents' mental health, and collateral benefits for the family environment, including improved child behavior. Nurses may have an integral role in interdisciplinary teams providing MBSR. PMID- 26379134 TI - The Electrophysiological Phenomenon of Alzheimer's Disease: A Psychopathology Theory. AB - The current understanding of Alzheimer's disease (AD) is based on the Abeta and tau pathology and the resulting neuropathological changes, which are associated with manifested clinical symptoms. However, electrophysiological brain changes may provide a more expansive understanding of AD. Hence, the objective of this systematic review is to propose a theory about the electrophysiological phenomenon of Alzheimer's disease (EPAD). The review of literature resulted from an extensive search of PubMed and MEDLINE databases. One-hundred articles were purposively selected. They provided an understanding of the concepts establishing the theory of EPAD (neuropathological changes, neurochemical changes, metabolic changes, and electrophysiological brain changes). Changes in the electrophysiology of the brain are foundational to the association or interaction of the concepts. Building on Berger's Psychophysical Model, it is evident that electrophysiological brain changes occur and affect cortical areas to generate or manifest symptoms from onset and across the stages of AD, which may be prior to pathological changes. Therefore, the interaction of the concepts demonstrates how the psychopathology results from affected electrophysiology of the brain. The theory of the EPAD provides a theoretical foundation for appropriate measurements of AD without dependence on neuropathological changes. Future research is warranted to further test this theory. Ultimately, this theory contributes to existing knowledge because it shows how electrophysiological changes are useful in understanding the risk and progression of AD across the stages. PMID- 26379135 TI - How Illegal Drug Use, Alcohol Use, Tobacco Use, and Depressive Symptoms Affect Adolescent Suicidal Ideation: A Secondary Analysis of the 2011 Youth Risk Behavior Survey. AB - The purpose of this study was to identify the major risk factors among adolescents who have either contemplated or attempted suicide. Along with successful suicides, suicide attempts and contemplation are coexisting factors that are prominent in the adolescent population and therefore warrant major concern. A secondary data analysis of the Youth Risk Behavior Survey (YRBS) was completed to explore the factors that may influence adolescents' thoughts or actions about suicidal behavior. The YRBS represents high-school students throughout 50 states. Nine questions from the YRBS were used to elicit information about the relationships among the risk factors: (1) Suicidal thoughts and attempts; (2) illegal drug use; (3) alcohol use; (4) tobacco use; and (5) depressive symptoms. Statistically significant relationships among the risk factors were found for adolescents. Adolescents considered suicide (15.8%); attempted suicide at least once (7.8%); were injured while attempting suicide (n = 2.7%). Our findings support the idea that illegal substance use can lead to suicidal thoughts and actions. Depression had a positive relationship with suicidal ideations, supporting similar studies suggesting that depression leads to suicidal action. PMID- 26379136 TI - Stress and Coping among Black Women Employed in Non-professional Service and Professional Occupations in Florida and Georgia. AB - Culture enhances the ability to address the stressors related to ethnicity/race, employment, and lifestyle. From this interaction, two coping patterns emerge: individualist-oriented or collectivist-oriented, of which women prefer the latter. However, there is limited knowledge about the impact of ethnicity/race on the coping strategies of Black working women in the USA. Therefore, the purpose of this cross-sectional survey was to examine the coping strategies of two groups of Black women, those who work in non-professional service-related jobs and those employed as professionals. We explored Black women from two southern states, Florida and Georgia, in their use of coping strategies for everyday stressors. A modified version of Lazarus and Folkman's Transactional Model was used as the framework of this study. The sample for this cross-sectional survey consisted of 313 Black women employed in non-professional service jobs and 343 in professional roles. The thoughts and actions related to coping in everyday stressors were measured with The Ways of Coping Questionnaire. PMID- 26379137 TI - A Hermeneutic Phenomenological Examination of the Lived Experience of Incarceration for those with Autism. AB - This study aimed to examine the lived experience of incarceration for those with autism using a hermeneutic phenomenological approach. Eight adults who were incarcerated in New South Wales, Australia, were interviewed. The lived experience of incarceration for the participants was about being in an unpredictable environment characterised by ever-changing routines and complex social situations. Participants were deprived of their ability to create predictability in their environment, and experienced confusion and distress when forced to comply with actions that were in conflict with their logic. Mental health nursing case management is recommended to address the needs of incarcerated persons with autism. PMID- 26379138 TI - Las Mujeres Nobles Identify their Meaning of Empowerment: A Participatory Data Analysis Project. PMID- 26379139 TI - Addressing Principles of Recovery to Engage Consumers in Outpatient Treatment. AB - Mental illness often requires hospitalization, with high readmission rates. One way to improve outcomes and reduce readmission rates is for consumers to attend outpatient appointments. However, a major challenge in delivery of mental health outpatient treatment is missed appointments. When consumers miss appointments for outpatient follow-up, they also miss an opportunity for recovery. Non-attendance rates in psychiatric outpatient clinics have been a topic of considerable interest and attendance at appointments has been used as an indicator of quality of service provision. Strategies used to address missed appointments have been met with minimal success in improving engagement in treatment and do not offer evidence-based guidance regarding solutions to this challenge. Simple measures to gain consumer feedback on levels of therapeutic alliance and engagement in shared decision-making are available and can be used in clinical sessions to support recovery-based care. Psychiatric mental health nurses can engage consumers in recovery-based services that have salience to motivate them to engage in treatment. PMID- 26379140 TI - Improving Psychiatric Nurses' Detection of Neuroleptic Malignant Syndrome. AB - Patients with psychiatric disorders receive nursing care in psychiatric units, medical units and long-term care facilities. Like other patients, their well being is reliant upon knowledgeable caregivers. The pharmacological interventions that patients are dependent on can have catastrophic effects; of particular concern is Neuroleptic Malignant Syndrome (NMS). This article affords a succinct review of the literature related to NMS and provides suggestions for psychiatric nurse educators to facilitate early recognition, thereby reducing mortality and morbidity. Emphasis is placed on educational tools to help reduce under detection. A case study illustrates how under-detection can lead to a near fatal outcome. PMID- 26379142 TI - Patterns of Lynx Predation at the Interface between Protected Areas and Multi-Use Landscapes in Central Europe. AB - In Central Europe, protected areas are too small to ensure survival of populations of large carnivores. In the surrounding areas, these species are often persecuted due to competition with game hunters. Therefore, understanding how predation intensity varies spatio-temporally across areas with different levels of protection is fundamental. We investigated the predation patterns of Eurasian lynx (Lynx lynx) on roe deer (Capreolus capreolus) and red deer (Cervus elaphus) in both protected areas and multi-use landscapes of the Bohemian Forest Ecosystem. Based on 359 roe and red deer killed by 10 GPS-collared lynx, we calculated the species-specific annual kill rates and tested for effects of season and lynx age, sex and reproductive status. Because roe and red deer in the study area concentrate in unprotected lowlands during winter, we modeled spatial distribution of kills separately for summer and winter and calculated-the probability of a deer killed by lynx and-the expected number of kills for areas with different levels of protection. Significantly more roe deer (46.05 74.71/year/individual lynx) were killed than red deer (1.57-9.63/year/individual lynx), more deer were killed in winter than in summer, and lynx family groups had higher annual kill rates than adult male, single adult female and subadult female lynx. In winter the probability of a deer killed and the expected number of kills were higher outside the most protected part of the study area than inside; in summer, this probability did not differ between areas, and the expected number of kills was slightly larger inside than outside the most protected part of the study area. This indicates that the intensity of lynx predation in the unprotected part of the Bohemian Forest Ecosystem increases in winter, thus mitigation of conflicts in these areas should be included as a priority in the lynx conservation strategy. PMID- 26379144 TI - Socioeconomic Status and Longitudinal Lung Function of Healthy Mexican Children. AB - INTRODUCTION: Our aim was to estimate the longitudinal effect of Socioeconomic status (SES) on lung function growth of Mexican children and adolescents. MATERIALS AND METHODS: A cohort of Mexican children in third grade of primary school was followed with spirometry twice a year for 6 years through secondary school. Multilevel mixed-effects lineal models were fitted for the spirometric variables of 2,641 respiratory-healthy Mexican children. Monthly family income (in 2002 U.S. dollars [USD]) and parents' years completed at school were used as proxies of SES. RESULTS: Individuals with higher SES tended to have greater height for age, and smaller sitting height/standing height and crude lung function. For each 1-year increase of parents' schooling, Forced expiratory volume in 1 sec (FEV1) and Forced vital capacity (FVC) increased 8.5 (0.4%) and 10.6 mL (0.4%), respectively (p <0.05) when models were adjusted for gender. Impact of education on lung function was reduced drastically or abolished on adjusting by anthropometric variables and ozone. CONCLUSIONS: Higher parental schooling and higher monthly family income were associated with higher lung function in healthy Mexican children, with the majority of the effect likely due to the increase in height-for-age. PMID- 26379143 TI - Global Morbidity and Mortality of Leptospirosis: A Systematic Review. AB - BACKGROUND: Leptospirosis, a spirochaetal zoonosis, occurs in diverse epidemiological settings and affects vulnerable populations, such as rural subsistence farmers and urban slum dwellers. Although leptospirosis is a life threatening disease and recognized as an important cause of pulmonary haemorrhage syndrome, the lack of global estimates for morbidity and mortality has contributed to its neglected disease status. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a systematic review of published morbidity and mortality studies and databases to extract information on disease incidence and case fatality ratios. Linear regression and Monte Carlo modelling were used to obtain age and gender adjusted estimates of disease morbidity for countries and Global Burden of Disease (GBD) and WHO regions. We estimated mortality using models that incorporated age and gender-adjusted disease morbidity and case fatality ratios. The review identified 80 studies on disease incidence from 34 countries that met quality criteria. In certain regions, such as Africa, few quality assured studies were identified. The regression model, which incorporated country-specific variables of population structure, life expectancy at birth, distance from the equator, tropical island, and urbanization, accounted for a significant proportion (R(2) = 0.60) of the variation in observed disease incidence. We estimate that there were annually 1.03 million cases (95% CI 434,000-1,750,000) and 58,900 deaths (95% CI 23,800-95,900) due to leptospirosis worldwide. A large proportion of cases (48%, 95% CI 40-61%) and deaths (42%, 95% CI 34-53%) were estimated to occur in adult males with age of 20-49 years. Highest estimates of disease morbidity and mortality were observed in GBD regions of South and Southeast Asia, Oceania, Caribbean, Andean, Central, and Tropical Latin America, and East Sub-Saharan Africa. CONCLUSIONS/SIGNIFICANCE: Leptospirosis is among the leading zoonotic causes of morbidity worldwide and accounts for numbers of deaths, which approach or exceed those for other causes of haemorrhagic fever. Highest morbidity and mortality were estimated to occur in resource-poor countries, which include regions where the burden of leptospirosis has been underappreciated. PMID- 26379146 TI - Preparation and structure of uranium-incorporated Gd2Zr2O7 compounds and their thermodynamic stabilities under oxidizing and reducing conditions. AB - Gd2Zr2O7 is being contemplated as a futuristic matrix for the incorporation of high-level radioactive nuclear waste. This compound has the unique ability to incorporate several fission products and heavy metal ions like uranium and thorium into its lattice sites without undergoing structural changes. X-ray diffraction analyses of Gd2-xUxZr2O7+delta samples indicate that the parent compound can incorporate a substantial amount of uranium, both under oxidizing and reducing conditions. The oxidation state of these samples was investigated by X-ray photoelectron spectroscopy. The thermodynamic stability of uranium substituted Gd2Zr2O7 is an important parameter that will govern the long-term storage of uranium and minor actinides in this matrix. High-temperature calorimetry has been used to investigate the stability of the Gd2-xUxZr2O7+delta (0.00 <= x <= 0.15) compositions. The standard molar free energy of the formation of Gd2-xUxZr2O7+delta (0.00 <= x <= 0.15) compositions has been estimated. From the free energy of formation data, the sample corresponding to x = 0.15 was found to be most stable in the Gd2-xUxZr2O7+delta (0.00 <= x <= 0.15) series. The relative stabilities of U(4+) and U(6+) substituted gadolinium zirconate have been discussed on the basis of the charge on the uranium ion and the incorporation of corresponding extra oxygen atoms into the lattice for charge compensation. PMID- 26379145 TI - Structural Properties of Gene Promoters Highlight More than Two Phenotypes of Diabetes. AB - Genome-wide association studies (GWAS) published in the last decade raised the number of loci associated with type 1 (T1D) and type 2 diabetes (T2D) to more than 50 for each of these diabetes phenotypes. The environmental factors seem to play an important role in the expression of these genes, acting through transcription factors that bind to promoters. Using the available databases we examined the promoters of various genes classically associated with the two main diabetes phenotypes. Our comparative analyses have revealed significant architectural differences between promoters of genes classically associated with T1D and T2D. Nevertheless, five gene promoters (about 16%) belonging to T1D and six gene promoters (over 19%) belonging to T2D have shown some intermediary structural properties, suggesting a direct relationship to either LADA (Latent Autoimmune Diabetes in Adults) phenotype or to non-autoimmune type 1 phenotype. The distribution of these promoters in at least three separate classes seems to indicate specific pathogenic pathways. The image-based patterns (DNA patterns) generated by promoters of genes associated with these three phenotypes support the clinical observation of a smooth link between specific cases of typical T1D and T2D. In addition, a global distribution of these DNA patterns suggests that promoters of genes associated with T1D appear to be evolutionary more conserved than those associated with T2D. Though, the image based patterns obtained by our method might be a new useful parameter for understanding the pathogenetic mechanism and the diabetogenic gene networks. PMID- 26379147 TI - Lymphocytic Esophagitis With CD4 T-cell-predominant Intraepithelial Lymphocytes and Primary Esophageal Motility Abnormalities: A Potential Novel Clinicopathologic Entity. AB - Lymphocytic esophagitis (LE) is an uncommon poorly defined histologic pattern. Its significance is largely unknown. The goal of our study was to characterize LE clinically, histologically, and immunophenotypically. Biopsies of 45 patients with LE and no intraepithelial granulocytes were selected throughout a 36-month period during routine diagnostic work. After reevaluation, complete absence of intraepithelial granulocytes was confirmed in 21 patients (LE-NG group), and few granulocytes were found in 24 patients (LE-FG). The control group consisted of 28 patients with active esophagitis consistent with reflux and overtly increased intraepithelial lymphocytes (REIL). The ratio of CD4:CD8 intraepithelial lymphocytes (IEL)>1 indicated predominance of CD4 IEL; the ratio <=1 indicated predominance of CD8 IEL. Dysphagia was the primary complaint in 71%, 54%, and 39% of the patients with LE-NG, LE-FG, and REIL, respectively (P=0.04, LE-NG vs. REIL). Importantly, primary esophageal motility abnormalities were found in 10/11 (91%) tested LE-NG patients, 6/10 (60%) LE-FG patients, and 6/11 (54%) REIL patients. CD4 IELs were predominant in 81%, 50%, and 39% of LE-NG, LE-FG, and REIL cases, respectively (P=0.004, LE-NG vs. REIL), and in 90%, 83%, and 88% of the cases with primary motility abnormalities from the same groups. The prevalence of primary motility abnormalities was significantly higher in patients with CD4-predominant esophagitis than in patients with CD8-predominant esophagitis from all groups (21/24 [83%] vs. 2/8 [25%], P=0.005). A distinctive type of LE with predominance of CD4 IEL is associated with primary motility abnormalities suggesting a diagnostic utility of evaluating CD4 and CD8 subpopulations of T cells in LE. PMID- 26379148 TI - Expression of S100 Protein in CD4-positive T-cell Lymphomas Is Often Associated With T-cell Prolymphocytic Leukemia. AB - S100 T-cell lymphomas are infrequent, and except 1 all have been CD4 negative. On the basis of an index case of CD4 S100 T-cell prolymphocytic leukemia (T-PLL), we studied S100 protein expression in 19 additional T-PLLs and 56 other T-cell lymphomas that are usually CD4, including 15 angioimmunoblastic T-cell lymphomas, 24 anaplastic large cell lymphomas (16 ALK and 8 ALK), 7 mycosis fungoides/Sezary syndrome, and 10 peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS). Two additional S100 CD4 PTCL, NOS cases were also reviewed. Thirty percent (6/20) of T-PLLs were S100 compared with 0/56 other T-cell lymphomas with previously unstudied S100 reactivity (40 CD4, 2 CD8, 11 CD4/CD8, 3 unknown) (P=0.0007). There were no significant differences between the S100 and S100 T-PLLs with regard to the male:female ratio (2:1 vs. 1:1), age (71.6+/-7.7 vs. 65.4+/-9.3), peripheral blood lymphocyte count (67.2+/-116.6 vs. 101.1+/-159.7*10/L), or median survival (463 vs. 578 d, where known). The 2 S100 PTCL, NOS cases occurred in a 7-year-old boy and a 45-year-old woman. Both had involvement of the bone marrow and peripheral blood but were morphologically unlike T-PLL and lacked TCL1 gene rearrangement. These results demonstrate that S100 T-cell lymphomas include a subset that are CD4 and most often, but not exclusively, are T-PLL. Although having diagnostic implications, there were no documented clinical differences between the S100 and S100 T-PLLs. PMID- 26379149 TI - IgG4-related Orbital Disease and Its Mimics in a Western Population. AB - Although chronic inflammatory disorders of the ocular adnexa are relatively common, their pathogenesis is in many cases poorly understood. Recent investigation suggests that many cases of sclerosing orbital inflammation are a manifestation of IgG4-related disease; however, most patients reported have been Asian, and it is not clear whether the results of studies from the Far East can be reliably extrapolated to draw conclusions about Western patients. We evaluated 38 cases previously diagnosed as orbital inflammatory pseudotumor or chronic dacryoadenitis to determine whether our cases fulfill the criteria for IgG4-RD (IgG4-related dacryoadenitis when involving the lacrimal gland, and IgG4-related sclerosing orbital inflammation when involving orbital soft tissue). Fifteen patients had IgG4-related dacryoadenitis or orbital inflammation. These patients included 9 men and 6 women, aged 24 to 77 years (median, 64 y). Lesions involved orbital soft tissue (8 cases), lacrimal gland (6 cases), and canthus (1 case). In 1 case, focal in situ follicular neoplasia was seen in a background of IgG4-RD. In another case, a clonal IGH gene rearrangement was detected. Four patients with IgG4-RD had evidence of IgG4-RD in other anatomic sites. Five patients, 1 man and 4 women, aged 26 to 74 years (median 50 y) had orbital lesions (2 involving lacrimal gland, 3 involving soft tissue) suspicious for, but not diagnostic of, IgG4-RD. Of 16 patients with IgG4-RD or probable IgG4-RD with information available regarding the course of their disease, 11 patients experienced recurrent or persistent orbital disease. However, no patient developed lymphoma, and no patient died of complications of IgG4-RD. Eighteen patients had lesions not representing IgG4-RD. They included 6 male and 12 female individuals aged 6 to 77 years (median, 47 y). These patients had a variety of diseases, including granulomatosis with polyangiitis (3 cases), Rosai-Dorfman disease (1 case), nonspecific chronic inflammation and fibrosis involving lacrimal gland or soft tissue (12 cases), and others. Clinical and pathologic findings among our patients with IgG4-RD involving the orbit are similar to those previously described in Asian patients. Careful evaluation of histologic and immunophenotypic features and clinical correlation are required to distinguish orbital IgG4-RD from other sclerosing inflammatory lesions in the orbit. PMID- 26379151 TI - Morphologic Features of ALK-negative Anaplastic Large Cell Lymphomas With DUSP22 Rearrangements. AB - Systemic anaplastic large cell lymphomas (ALCLs) are classified into ALK-positive and ALK-negative types. We recently reported that ALK-negative ALCLs are genetically heterogenous. The largest subset, representing 30% of cases, had rearrangements of the DUSP22 locus. These cases had favorable outcomes similar to ALK-positive ALCL, and superior to other ALK-negative ALCLs. Here, we examined the morphologic features of these cases in more detail. First, we conducted blinded review of hematoxylin and eosin slides of 108 ALCLs from our previous study, scoring cases for the presence of 3 histologic patterns and 5 cell types. Cases then were unblinded and re-reviewed to understand these features further. DUSP22-rearranged ALCLs were more likely than other ALK-negative ALCLs to have so called doughnut cells (23% vs. 5%; P=0.039), less likely to have pleomorphic cells (23% vs. 49%; P=0.042), and nearly always (95%) had areas with sheet-like growth (common pattern). To examine the reproducibility of these findings, we conducted blinded review of hematoxylin and eosin slides of 46 additional ALK negative ALCLs using a 0 to 3 scoring system to predict likelihood of DUSP22 rearrangement, the results of which correlated strongly with subsequent findings by fluorescence in situ hybridization (P<0.0001). Although all ALCLs share certain morphologic features, ALCLs with DUSP22 rearrangements show significant differences from other ALK-negative ALCLs, typically showing sheets of hallmark cells with doughnut cells and few large pleomorphic cells. These morphologic findings and our previous outcome data suggest that ALK-positive ALCLs and DUSP22 rearranged ALCLs represent prototypical ALCLs, whereas ALCLs lacking rearrangements of both DUSP22 and ALK require further study. PMID- 26379150 TI - Investigating Diagnostic Problems of CIN1 and CIN2 Associated With High-risk HPV by Combining the Novel Molecular Biomarker PanHPVE4 With P16INK4a. AB - Grading cervical intraepithelial neoplasia (CIN) determines clinical management of women after abnormal cytology with potential for overdiagnosis and overtreatment. We studied a novel biomarker of human papillomavirus (HPV) life cycle completion (panHPVE4), in combination with the minichromosome maintenance (MCM) protein cell-cycle marker and the p16INK4a transformation marker, to improve CIN diagnosis and categorization. Scoring these biomarkers alongside CIN grading by 3 pathologists was performed on 114 cervical specimens with high-risk (HR) HPV. Interobserver agreement for histopathology was moderate (kappa=0.43 for CIN1/negative, 0.54 for CIN2/<=CIN1, and 0.36 for CIN3). Agreement was good or excellent for biomarker scoring (E4: kappa=0.896; 95% confidence interval [CI]: 0.763-0.969; p16INK4a : kappa=0.798; 95% CI: 0.712-0.884; MCM: kappa=0.894; 95% CI: NC (this quantity cannot be calculated). Biomarker expression was studied by immunofluorescence and immunohistochemistry and was correlated with 104 final CIN diagnoses after histologic review. All 25 histologically negative specimens were p16INK4a and panHPVE4 negative, although 9 were MCM-positive. There were variable extents of p16INK4a positivity in 11/11 CIN1 and extensive panHPVE4 staining in 9/11. Ten CIN2 lesions expressed panHPVE4 and p16INK4a, and 13 CIN2 expressed only p16INK4a. CIN3 showed extensive p16INK4a positivity with no/minimal panHPVE4 staining. PanHPVE4, unlike MCM, distinguished CIN1 from negative. PanHPVE4 with p16INK4a separated CIN2/3 showing only expression of p16INK4a, indicating transforming HR-HPV E7 expression, from CIN1/2 showing completion of HR-HPV life cycle by E4 expression and variable p16INK4a expression. PanHPVE4 and p16INK4a staining are complementary markers that could provide simple, reliable support for diagnosing CIN. Their value in distinguishing CIN1/2 that supports HR-HPV life-cycle completion (and which might ultimately regress) from purely transforming CIN2/3 needing treatment warrants further research. PMID- 26379152 TI - Primary CNS T-cell Lymphomas: A Clinical, Morphologic, Immunophenotypic, and Molecular Analysis. AB - Primary central nervous system (CNS) lymphomas are relatively rare with the most common subtype being diffuse large B-cell lymphoma. Primary CNS T-cell lymphomas (PCNSTL) account for <5% of CNS lymphomas. We report the clinical, morphologic, immunophenotypic, and molecular characteristics of 18 PCNSTLs. Fifteen cases were classified as peripheral T-cell lymphoma, not otherwise specified, 2 of which were of gammadelta T-cell derivation and 1 was TCR silent; there was 1 anaplastic large cell lymphoma, ALK-positive and 2 anaplastic large cell lymphoma, ALK negative. Median age was 58.5 years (range, 21 to 81 y), with an M:F ratio of 11:7. Imaging results showed that 15 patients had supratentorial lesions. Regardless of subtype, necrosis and perivascular cuffing of tumor cells were frequently observed (11/18 cases). CD3 was positive in all cases but 1; 10/17 were CD8-positive, and 5/17 were CD4-positive. Most cases studied had a cytotoxic phenotype with expression of TIA1 (13/15) and granzyme-B (9/13). Polymerase chain reaction analysis of T-cell receptor gamma rearrangement confirmed a T-cell clone in 14 cases with adequate DNA quality. Next-generation sequencing showed somatic mutations in 36% of cases studied; 2 had >1 mutation, and none showed overlapping mutations. These included mutations in DNMT3A, KRAS, JAK3, STAT3, STAT5B, GNB1, and TET2 genes, genes implicated previously in other T-cell neoplasms. The outcome was heterogenous; 2 patients are alive without disease, 4 are alive with disease, and 6 died of disease. In conclusion, PCNSTLs are histologically and genomically heterogenous with frequent phenotypic aberrancy and a cytotoxic phenotype in most cases. PMID- 26379153 TI - A Method to Constrain Genome-Scale Models with 13C Labeling Data. AB - Current limitations in quantitatively predicting biological behavior hinder our efforts to engineer biological systems to produce biofuels and other desired chemicals. Here, we present a new method for calculating metabolic fluxes, key targets in metabolic engineering, that incorporates data from 13C labeling experiments and genome-scale models. The data from 13C labeling experiments provide strong flux constraints that eliminate the need to assume an evolutionary optimization principle such as the growth rate optimization assumption used in Flux Balance Analysis (FBA). This effective constraining is achieved by making the simple but biologically relevant assumption that flux flows from core to peripheral metabolism and does not flow back. The new method is significantly more robust than FBA with respect to errors in genome-scale model reconstruction. Furthermore, it can provide a comprehensive picture of metabolite balancing and predictions for unmeasured extracellular fluxes as constrained by 13C labeling data. A comparison shows that the results of this new method are similar to those found through 13C Metabolic Flux Analysis (13C MFA) for central carbon metabolism but, additionally, it provides flux estimates for peripheral metabolism. The extra validation gained by matching 48 relative labeling measurements is used to identify where and why several existing COnstraint Based Reconstruction and Analysis (COBRA) flux prediction algorithms fail. We demonstrate how to use this knowledge to refine these methods and improve their predictive capabilities. This method provides a reliable base upon which to improve the design of biological systems. PMID- 26379156 TI - Introducing specificity and sensitivity in imaging MS. PMID- 26379154 TI - Association of the FCN2 Gene Single Nucleotide Polymorphisms with Susceptibility to Pulmonary Tuberculosis. AB - Ficolin-2 (FCN2) is an innate immune pattern recognition molecule that can activate the complement pathway, opsonophagocytosis, and elimination of the pathogens. The present study aimed to investigate the association of the FCN2 gene single nucleotide polymorphisms (SNPs) with susceptibility to pulmonary tuberculosis (TB). A total of seven SNPs in exon 8 (+6359 C>T and +6424 G>T) and in the promoter region (-986 G>A, -602 G>A, -557 A>G, -64 A>C and -4 A>G) of the FCN2 gene were genotyped using the PCR amplification and DNA sequencing methods in the healthy controls group (n = 254) and the pulmonary TB group (n = 282). The correlation between SNPs and pulmonary TB was analyzed using the logistic regression method. The results showed that there were no significant differences in the distribution of allelic frequencies of seven SNPs between the pulmonary TB group and the healthy controls group. However, the frequency of the variant homozygous genotype (P = 0.037, -557 A>G; P = 0.038, -64 A>C; P = 0.024, +6424 G>T) in the TB group was significantly lower than the control group. After adjustment for age and gender, these variant homozygous genotypes were found to be recessive models in association with pulmonary TB. In addition, -64 A>C (P = 0.047) and +6424 G>T (P = 0.03) were found to be codominant models in association with pulmonary TB. There was strong linkage disequilibrium (r2 > 0.80, P < 0.0001) between 7 SNPs except the -602 G>A site. Therefore, -557 A>G, -64 A>C and +6424 G>T SNPs of the FCN2 gene were correlated with pulmonary TB, and may be protective factors for TB. This study provides a novel idea for the prevention and control of TB transmission from a genetics perspective. PMID- 26379155 TI - Ultraconserved Elements Sequencing as a Low-Cost Source of Complete Mitochondrial Genomes and Microsatellite Markers in Non-Model Amniotes. AB - Sequence capture of ultraconserved elements (UCEs) associated with massively parallel sequencing has become a common source of nuclear data for studies of animal systematics and phylogeography. However, mitochondrial and microsatellite variation are still commonly used in various kinds of molecular studies, and probably will complement genomic data in years to come. Here we show that besides providing abundant genomic data, UCE sequencing is an excellent source of both sequences for microsatellite loci design and complete mitochondrial genomes with high sequencing depth. Identification of dozens of microsatellite loci and assembly of complete mitogenomes is exemplified here using three species of Poospiza warbling finches from southern and southeastern Brazil. This strategy opens exciting opportunities to simultaneously analyze genome-wide nuclear datasets and traditionally used mtDNA and microsatellite markers in non-model amniotes at no additional cost. PMID- 26379159 TI - The Effect of Host-Plant Phylogenetic Isolation on Species Richness, Composition and Specialization of Insect Herbivores: A Comparison between Native and Exotic Hosts. AB - Understanding the drivers of plant-insect interactions is still a key issue in terrestrial ecology. Here, we used 30 well-defined plant-herbivore assemblages to assess the effects of host plant phylogenetic isolation and origin (native vs. exotic) on the species richness, composition and specialization of the insect herbivore fauna on co-occurring plant species. We also tested for differences in such effects between assemblages composed exclusively of exophagous and endophagous herbivores. We found a consistent negative effect of the phylogenetic isolation of host plants on the richness, similarity and specialization of their insect herbivore faunas. Notably, except for Jaccard dissimilarity, the effect of phylogenetic isolation on the insect herbivore faunas did not vary between native and exotic plants. Our findings show that the phylogenetic isolation of host plants is a key factor that influences the richness, composition and specialization of their local herbivore faunas, regardless of the host plant origin. PMID- 26379157 TI - Genetic Diversity and Natural Selection of the Plasmodium knowlesi Circumsporozoite Protein Nonrepeat Regions. AB - BACKGROUND: Plasmodium knowlesi is a simian malaria parasite that has been identified to cause malaria in humans. To date, several thousand cases of human knowlesi malaria have been reported around Southeast Asia. Thus far, there is no detailed study on genetic diversity and natural selection of P. knowlesi circumsporozoite protein (CSP), a prominent surface antigen on the sporozoite of the parasite. In the present study, the genetic diversity and natural selection acting on the nonrepeat regions of the gene encoding P. knowlesi CSP were investigated, focusing on the T-cell epitope regions at the C-terminal of the protein. METHODS: Blood samples from 32 knowlesi malaria patients and 2 wild monkeys (Macaca fascicularis) were used. The CSP of the P. knowlesi isolates was amplified by PCR, cloned into Escherichia coli, and sequenced. The nonrepeat regions of the CSP gene were analysed for genetic diversity, natural selection and haplotypic grouping using MEGA5 and DnaSP version 5.10.00 programmes. A haplotype network was constructed based on the C-terminal (Th2R/Th3R) T-cell epitope regions using the Median-Joining method in the NETWORK version 4.6.1.2 programme. Previously published sequences from other regions (Malaysia Borneo, Singapore) were also included in the analysis. RESULTS: A total of 123 P. knowlesi CSP sequences were analysed. Multiple sequence alignment revealed 58 amino acid changes, and 42 novel amino acid haplotypes were identified. Polymorphism was higher in the C-terminal Th2R/Th3R epitope (pi = 0.0293, n = 123) region compared to the overall combined nonrepeat regions (pi = 0.0120, n = 123). Negative natural selection was observed within the nonrepeat regions of the CSP gene. Within the C-terminal Th2R/Th3R epitope regions, there was evidence of slight positive selection. Based on haplotype network analysis of the Th2R/Th3R regions, five abundant haplotypes were identified. Sharing of haplotypes between humans and macaques were observed. CONCLUSION: This study contributes to the understanding of the type and distribution of naturally occurring polymorphism in the P. knowlesi CSP gene. This study also provides a measurement of the genetic diversity of P. knowlesi and identifies the predominant haplotypes within Malaysia based on the C-terminal Th2R/Th3R regions. PMID- 26379160 TI - Respiratory Syncytial Virus Preterm (32-36 Completed Weeks of Gestation) Risk Estimation Measure for RSV Hospitalization in Ireland: A Prospective Study. AB - BACKGROUND: In several countries, respiratory syncytial virus prophylaxis is offered to late preterm infants who are at escalated risk of respiratory syncytial virus hospitalization (RSVH). However, targeted prophylaxis should be informed by country-specific data. This study, which uniquely includes 36 weeks of gestational age (GA) infants, aims to establish the risk factors for RSVH in 32-36 weeks of GA infants in Ireland. METHODS: A prospective observational study at 13 hospitals of laboratory-confirmed RSVH in nonprophylaxed 32-36 weeks of GA infants was conducted from July 2011 to February 2014. Baseline and first-year clinical data were analyzed by using SPSS software Version 22 (IBM Corp, Armonk, NY). Significant (P < 0.05) variables were entered into multiple logistic regression to determine the independent risk factors for RSVH. RESULTS: Sixty three percent of eligible infants (1825 of 2877) were recruited. The RSVH rate was 3.6% (65 of 1807 analyzed infant records). There was no RSV-attributable mortality. Twelve infants required intensive care. Of the 15 variables correlating to RSVH, 5 independent risk factors were identified: older siblings [odds ratio (OR): 3.8; 95% confidence interval (CI): 1.97-7.41], being Caucasian (OR: 2.3; 95% CI: 1.04-5.29), neonatal respiratory morbidity (OR: 2.2; 95% CI: 1.28-3.94); birth July 15 to December 15 (OR: 2.1; 95% CI: 1.09-3.92) and family history of asthma (OR: 1.9; 95% CI: 1.01-3.39). Birth from 36 weeks to 36 + 6 days mitigated RSVH risk (relative risk: 0.58; 95% CI: 0.34-0.99); however, risk factors were similar to the 32-35 weeks of GA cohort. CONCLUSION: Neonatal respiratory morbidity or being Caucasian were the population-specific independent risk factors for RSVH in 32-36 weeks of GA in Ireland, whereas the other identified independent risk factors mirrored those established in previous studies. PMID- 26379158 TI - The Role of ARF6 in Biliary Atresia. AB - BACKGROUND & AIMS: Altered extrahepatic bile ducts, gut, and cardiovascular anomalies constitute the variable phenotype of biliary atresia (BA). METHODS: To identify potential susceptibility loci, Caucasian children, normal (controls) and with BA (cases) at two US centers were compared at >550000 SNP loci. Systems biology analysis was carried out on the data. In order to validate a key gene identified in the analysis, biliary morphogenesis was evaluated in 2-5-day post fertilization zebrafish embryos after morpholino-antisense oligonucleotide knockdown of the candidate gene ADP ribosylation factor-6 (ARF6, Mo-arf6). RESULTS: Among 39 and 24 cases at centers 1 and 2, respectively, and 1907 controls, which clustered together on principal component analysis, the SNPs rs3126184 and rs10140366 in a 3' flanking enhancer region for ARF6 demonstrated higher minor allele frequencies (MAF) in each cohort, and 63 combined cases, compared with controls (0.286 vs. 0.131, P = 5.94x10-7, OR 2.66; 0.286 vs. 0.13, P = 5.57x10-7, OR 2.66). Significance was enhanced in 77 total cases, which included 14 additional BA genotyped at rs3126184 only (p = 1.58x10-2, OR = 2.66). Pathway analysis of the 1000 top-ranked SNPs in CHP cases revealed enrichment of genes for EGF regulators (p<1 x10-7), ERK/MAPK and CREB canonical pathways (p<1 x10-34), and functional networks for cellular development and proliferation (p<1 x10-45), further supporting the role of EGFR-ARF6 signaling in BA. In zebrafish embryos, Mo-arf6 injection resulted in a sparse intrahepatic biliary network, several biliary epithelial cell defects, and poor bile excretion to the gall bladder compared with uninjected embryos. Biliary defects were reproduced with the EGFR-blocker AG1478 alone or with Mo-arf6 at lower doses of each agent and rescued with arf6 mRNA. CONCLUSIONS: The BA-associated SNPs identify a chromosome 14q21.3 susceptibility locus encompassing the ARF6 gene. arf6 knockdown in zebrafish implicates early biliary dysgenesis as a basis for BA, and also suggests a role for EGFR signaling in BA pathogenesis. PMID- 26379161 TI - A Prospective Multicenter Study of Leukopenia in Infants Younger Than Ninety Days With Fever Without Source. AB - BACKGROUND: Little is known about the value of leukopenia for assessing the risk of having a bacterial infection in young febrile infants. METHODS: Infants younger than 90 days with fever without source were prospectively recruited between October 2011 and September 2013 in 19 Spanish Pediatric Emergency Departments. We analyzed the prevalence of invasive bacterial infection (IBI, positive blood or cerebrospinal fluid culture) and non-IBI (urinary tract infections and any other microbiologically confirmed bacterial infection excluding IBIs) by leukocyte count and general appearance. RESULTS: Among the 3401 infants recruited, 680 were diagnosed with non-IBIs (19.9%) and 107 with IBIs (3.1%). Overall, 244 infants had leukopenia (<5000 cells/mcL), 2369 a normal leukocyte count and 790 leukocytosis (>15,000 cells/mcL). Among the 3034 well appearing patients, those with leukopenia had a lower prevalence of non-IBI [8.1% vs. 14.7%; odds ratio (OR) 0.51 (95% confidence interval (CI): 0.29-0.88)] and a similar prevalence of IBI [2.5% vs. 2.0%; OR, 1.20 (95% CI: 0.44-3.44)] compared with those with a normal leukocyte count. Among the 367 not-well-appearing infants, those with leukopenia had a similar prevalence of non-IBI [8.9% vs. 14.7%; OR, 0.57 (95% CI: 0.16-1.79)] and a higher prevalence of IBI [17.8% vs. 6.9%; OR, 2.90 (95% CI: 1.06-7.78)]. In the subgroup of well-appearing infants 22 90 days old without leukocyturia according to urine dipstick results, prevalence of both non-IBIs and IBIs was similar in patients with leukopenia and those with a normal leukocyte count. CONCLUSION: Leukopenia in well-appearing young febrile infants should not be considered a risk factor for having a bacterial infection. PMID- 26379162 TI - Severe Upper Extremity Dysfunction After 4CMenB Vaccination in a Young Infant. AB - The 4-component meningococcal serogroup B vaccine 4CMenB (Bexsero) is the first vaccine against this serogroup and has been approved by licensing authorities in Europe, Canada and Australia. Therefore, the vaccine may enter soon nationwide vaccine recommendation schemes. We report on a case of a 5-month-old infant who developed prolonged upper extremity dysfunction after the second injection of the 4CMenB vaccine in the left deltoid muscle and was concomitantly applied with 2 routine vaccinations. Myositis, periostitis, (peri-) vasculitis and axillary inflammation were confirmed by magnetic resonance imaging. Two months after initial initiation of an anti-inflammatory and an antibiotic treatment, symptoms completely resolved. Administration of 3 vaccines requires clear recommendations for the preferred injection site in infants because increased reactogenicity of 4CMenB may lead to local severe adverse events. PMID- 26379163 TI - Efavirenz Capsule Sprinkle and Liquid Formulations With Didanosine and Emtricitabine in HIV-1-infected Infants and Children 3 Months to 6 Years of Age: Study AI266-922. AB - BACKGROUND: AI266-922 was an open-label, dose-ranging study that assessed the pharmacokinetics, safety and efficacy of efavirenz (EFV) in children (3 months to 6 years). METHODS: Antiretroviral-naive and antiretroviral-experienced HIV-1 infected children received once-daily EFV as oral solution or capsule sprinkle plus didanosine and emtricitabine (FTC). Pharmacokinetic analyses were undertaken at week 2 and repeated at weeks 10 and 18 after an EFV dose change or switch from oral solution to capsule sprinkle. RESULTS: Thirty-seven subjects were treated. EFV area under the plasma concentration-time curve over 1 dosing interval from time 0 to 24 hours postdose values were generally suboptimal (<110 MUM * h) in subjects younger than 3 years treated with oral solution; these subjects switched to capsule sprinkle. Twenty of 21 subjects younger than 3 years treated with capsule sprinkle achieved an EFV area under the plasma concentration-time curve over 1 dosing interval from time 0 to 24 hours postdose value >110 MUM * h, although higher initial doses were administered in this age group. Interpatient variability in EFV exposure was high. By week 48, 77.8% and 63.0% of subjects achieved HIV-RNA <400 and <50 copies/mL, respectively. Median changes in log10 HIV-RNA and CD4 percentage from baseline were -3.18 copies/mL and +6%, respectively. Two (5.4%) patients discontinued because of adverse events (AEs). Serious AEs occurred in 20 (54.1%) subjects. Common AEs were diarrhea (49%), nasopharyngitis (35%) and pneumonia (30%). Overall, 43% of subjects with suboptimal EFV exposure at week 2 developed resistance. CONCLUSIONS: Once-daily EFV, given as capsule sprinkle, achieved target exposures in this study although doses were 2-3 times higher than Food and Drug Administration-approved doses for children younger than 3 years. These data are useful for dose selection modeling and simulation; however, Food and Drug Administration-approved doses should be used clinically. EFV + didanosine + FTC was efficacious with no new pediatric safety findings reported. PMID- 26379164 TI - Reduced All-cause Child Mortality After General Measles Vaccination Campaign in Rural Guinea-Bissau. AB - BACKGROUND: Randomized trials have shown that measles vaccine (MV) prevents nonmeasles deaths. MV campaigns are conducted to eliminate measles infection. The overall mortality effect of MV campaigns has not been studied. METHODS: Bandim Health Project (BHP) surveys children aged 0-4 years in rural Guinea-Bissau through a health and demographic surveillance system. A national MV campaign in 2006 targeted children aged 6 months to 15 years. In a Cox proportional hazards model with age as the underlying timescale, we compared mortality of children aged 6-59 months after the campaign with mortality in the same age group during the 2 previous years. RESULTS: Eight thousand one hundred fifty eight children aged 6-59 months were under BHP surveillance during the 2006 campaign and 7999 and 8108 during similar periods in 2004 and 2005. At least 90% of the eligible children received MV in the campaign. There were 161 nonaccident deaths in 12 months after the campaign compared with 203 and 206 deaths in the 2 previous years, the adjusted mortality rate ratio (aMRR) comparing all children in 2006 with all children in 2004 to 2005 being 0.80 (95% confidence interval: 0.66 0.96). Censoring deaths caused by measles infection, the aMRR was 0.83 (0.69 1.00). The mortality reduction was separately significant for girls [aMRR = 0.74 (0.56-0.97)] and for children who also had received routine MV [MRR = 0.59 (0.36 0.99)]. CONCLUSIONS: Mortality levels were stable during 2004 and 2005, but a significant drop occurred after the 2006 MV campaign and was not explained by the prevention of measles deaths. If MV campaigns reduce nonmeasles-related mortality, the policies for measles vaccination should take this into account. PMID- 26379165 TI - Extrapolation of Valacyclovir Posology to Children Based on Pharmacokinetic Modeling. AB - BACKGROUND: Valacyclovir is a prodrug of acyclovir. Although acyclovir is approved for children in Europe, valacyclovir is not approved, despite being used off-label. The aim of the study was to extrapolate the approved dosages of acyclovir, to valacyclovir dosages, in children using Monte Carlo simulations based on the population pharmacokinetic (PopPK) models of valacyclovir and acyclovir. METHODS: Assuming that the recommended dosages of acyclovir are efficacious, a PopPK model of acyclovir was used to perform simulations to determine a critical concentration (Ccrit) for which a target criterion is fulfilled, ie, 90% of the simulated patients have acyclovir levels above Ccrit for at least half the time. The same was done for a secondary target, drug exposure, determining a critical area under the curve in 24 hours at steady state. Then a PopPK model of valacyclovir was used to determine by simulations, dosage regimens that fulfill the criteria for both targets. This was repeated for various indications and age groups. RESULTS: Indicatively, for the treatment of varicella zoster virus, in ages 2-12 years, Ccrit and critical area under the curve in 24 hours at steady state were found to be 0.39 mg/L and 9.6 mg/L * h, respectively, using the acyclovir approved doses 20 mg/kg 4 times daily. For these breakpoints, a 20 mg/kg, 3 times daily, valacyclovir dose achieves the targets in 97% and 100% of the patients, respectively. We found that some patients receive higher than the ideal doses of acyclovir. CONCLUSIONS: Simulations were used to determine the appropriate doses of valacyclovir in children to support a pediatric investigation plan targeting a paediatric-use marketing authorization application in the European Medicines Agency. PMID- 26379166 TI - Interferon-gamma Immunotherapy in a Patient With Refractory Disseminated Candidiasis. AB - Despite advances in supportive care and novel antifungal agents, mortality caused by invasive Candida infection is high. A 3-year-old boy with disseminated Candida dubliniensis infection during induction chemotherapy for acute lymphoblastic leukemia deteriorated despite resolution of neutropenia and appropriate antifungal treatment. Monocyte human leukocyte antigen-DR expression was extremely low, suggesting immunoparalysis. Adjuvant immunotherapy with interferon gamma restored the immune response, which was accompanied by clinical and radiographic recovery. PMID- 26379167 TI - Guillain-BarrE Syndrome After Immunization in Canadian Children (1996-2012). AB - Guillain-Barre syndrome (GBS) cases admitted to Canadian pediatric tertiary care centers were ascertained through active surveillance. From 1996 to 2012, 246 cases were identified, and 24 (10%) had onset <=30 days after immunization. Annual rate of postimmunization GBS was 2.0 per 100,000 hospitalizations. Postimmunization GBS was an infrequent cause of pediatric hospitalization. PMID- 26379168 TI - Culture-positive Pediatric Tuberculosis in Toronto, Ontario: Sources of Infection and Relationship of Birthplace and Mycobacterial Lineage to Phenotype. AB - BACKGROUND: Few data relate Mycobacterium tuberculosis (Mtb) lineage and disease phenotype in the pediatric population or examine the contribution of travel to the tuberculosis (TB)-endemic country in North America. We examined clinical, demographic and Mtb genotype data from patients with TB who were treated in Toronto between 2002 and 2012. METHODS: Consecutive Mtb culture-positive, pediatric patients were included. Clinical data were collected from a prospectively populated clinical database. Mtb case isolate genotypes were identified using Mycobacterial Interspersed Repetitive Units-Variable Number Tandem Repeat (MIRU-VNTR) and spoligotyping and were categorized into phylogeographic lineages for analysis. RESULTS: The 77 patients included 30.4% of all culture-positive pediatric TB cases in Ontario from 2002 to 2012. Seventy-six (99%) patients were first or second generation Canadians. Foreign-born patients were more likely to have extrathoracic disease [odds ratios (OR) = 3.0; 95% confidence interval (CI): 1.04-8.71; P < 0.05] and less likely to have a genotype match in the Public Health Ontario Laboratories database [OR = 0.32 (95% CI: 0.11 0.90); P < 0.05] than Canadian-born patients. For those without a known TB contact, Canadian-born patients were more likely to have travelled to a TB endemic country [OR = 13.0 (95% CI: 2.5-78.5); P < 0.001]. Extrathoracic disease was less likely in patients infected with the East Asian Mtb lineage [OR = 0.1 (95% CI: 0.01-0.9); P < 0.05] and more likely in those infected with the Indo Oceanic Mtb lineage [OR = 5.4 (95% CI: 1.5-19.2); P < 0.05]. CONCLUSIONS: Travel to TB-endemic countries likely plays an important part in the etiology of pediatric TB infection and disease, especially in Canadian-born children. Mtb lineage seems to contribute to disease phenotype in children as it has been described in adults. PMID- 26379169 TI - Reducing CD4 Monitoring in Children on Antiretroviral Therapy With Virologic Suppression. AB - BACKGROUND: Ongoing CD4 monitoring in patients on antiretroviral therapy (ART) with viral suppression has been questioned. We evaluated the probability of CD4 decline in children with viral suppression and CD4 recovery after 1 year on ART. METHODS: We included children from 8 South African cohorts with routine HIV-RNA monitoring if (1) they were "responders" [HIV-RNA < 400 copies/mL and no severe immunosuppression after >=1 year on ART (time 0)] and (2) >=1 HIV-RNA and CD4 measurement within 15 months of time 0. We determined the probability of CD4 decline to World Health Organization-defined severe immunosuppression for 3 years after time 0 if viral suppression was maintained. Follow-up was censored at the earliest of the following dates: the day before first HIV-RNA measurement >400 copies/mL; day before a >15-month gap in testing and date of death, loss to follow-up, transfer out or database closure. RESULTS: Among 5984 children [median age at time 0: 5.8 years (interquartile range: 3.1-9.0)], 270 children experienced a single CD4 decline to severe immunosuppression within 3 years of time 0 with probability of 6.6% (95% CI: 5.8-7.4). A subsequent CD4 measurement within 15 months of the first low measurement was available for 63% of children with CD4 decline and 86% showed CD4 recovery. The probability of CD4 decline was lowest (2.8%) in children aged 2 years or older with no or mild immunosuppression and on ART for <18 months at time 0. This group comprised 40% of children. CONCLUSIONS: This finding suggests that it may be safe to stop routine CD4 monitoring in children older than 2 years and rely on virologic monitoring alone. PMID- 26379170 TI - Use of High-Frequency In-Home Monitoring Data May Reduce Sample Sizes Needed in Clinical Trials. AB - BACKGROUND: Trials in Alzheimer's disease are increasingly focusing on prevention in asymptomatic individuals. This poses a challenge in examining treatment effects since currently available approaches are often unable to detect cognitive and functional changes among asymptomatic individuals. Resultant small effect sizes require large sample sizes using biomarkers or secondary measures for randomized controlled trials (RCTs). Better assessment approaches and outcomes capable of capturing subtle changes during asymptomatic disease stages are needed. OBJECTIVE: We aimed to develop a new approach to track changes in functional outcomes by using individual-specific distributions (as opposed to group-norms) of unobtrusive continuously monitored in-home data. Our objective was to compare sample sizes required to achieve sufficient power to detect prevention trial effects in trajectories of outcomes in two scenarios: (1) annually assessed neuropsychological test scores (a conventional approach), and (2) the likelihood of having subject-specific low performance thresholds, both modeled as a function of time. METHODS: One hundred nineteen cognitively intact subjects were enrolled and followed over 3 years in the Intelligent Systems for Assessing Aging Change (ISAAC) study. Using the difference in empirically identified time slopes between those who remained cognitively intact during follow-up (normal control, NC) and those who transitioned to mild cognitive impairment (MCI), we estimated comparative sample sizes required to achieve up to 80% statistical power over a range of effect sizes for detecting reductions in the difference in time slopes between NC and MCI incidence before transition. RESULTS: Sample size estimates indicated approximately 2000 subjects with a follow-up duration of 4 years would be needed to achieve a 30% effect size when the outcome is an annually assessed memory test score. When the outcome is likelihood of low walking speed defined using the individual-specific distributions of walking speed collected at baseline, 262 subjects are required. Similarly for computer use, 26 subjects are required. CONCLUSIONS: Individual specific thresholds of low functional performance based on high-frequency in-home monitoring data distinguish trajectories of MCI from NC and could substantially reduce sample sizes needed in dementia prevention RCTs. PMID- 26379171 TI - Knocking on Closed Doors: Host Interferons Dynamically Regulate Blood-Brain Barrier Function during Viral Infections of the Central Nervous System. PMID- 26379173 TI - New Guidelines for Spontaneous Intracranial Hemorrhage: A Roadmap for Optimizing Outcomes. PMID- 26379174 TI - Randomized Clinical Trial of Balloon-Expandable Intracranial Stenting Versus Aggressive Medical Therapy for Symptomatic Intracranial Arterial Stenosis. PMID- 26379175 TI - The Central Role of Glycolysis in Glioblastoma. PMID- 26379176 TI - New Molecular Insights and Potential Therapies for Diffuse Intrinsic Pontine Glioma. PMID- 26379177 TI - Buzz Kill: Neuronal Activity Promotes Glioma Proliferation. PMID- 26379178 TI - Sensitization of Glioblastoma Cells to Irradiation by Modulating the Glucose Metabolism. PMID- 26379179 TI - A Novel Device for Direct Determination of Tumor Chemotherapeutic Sensitivity. PMID- 26379180 TI - Deep Brain Stimulation Therapy in Parkinson Disease: The Role of Cortical Phase Amplitude Coupling Reduction. PMID- 26379182 TI - Aggregation-based detection of M. smegmatis using D-arabinose-functionalized fluorescent silica nanoparticles. AB - Fluorescein-doped silica nanoparticles (FSNPs) functionalized with D-arabinose (Ara) showed strong interactions with Mycobacterium smegmatis (M. smegmatis) and caused the bacteria to aggregate. This aggregate formation was used as a means to detect M. smegmatis at the concentration of 10(4) CFU per mL. PMID- 26379184 TI - Correction: Comprehensive Mapping of the Escherichia coli Flagellar Regulatory Network. PMID- 26379183 TI - Magnetic Resonance Imaging Is Sensitive to Pathological Amelioration in a Model for Laminin-Deficient Congenital Muscular Dystrophy (MDC1A). AB - PURPOSE: To elucidate the reliability of MRI as a non-invasive tool for assessing in vivo muscle health and pathological amelioration in response to Losartan (Angiotensin II Type 1 receptor blocker) in DyW mice (mouse model for Laminin deficient Congenital Muscular Dystrophy Type 1A). METHODS: Multiparametric MR quantifications along with histological/biochemical analyses were utilized to measure muscle volume and composition in untreated and Losartan-treated 7-week old DyW mice. RESULTS: MRI shows that DyW mice have significantly less hind limb muscle volume and areas of hyperintensity that are absent in WT muscle. DyW mice also have significantly elevated muscle levels (suggestive of inflammation and edema). Muscle T2 returned to WT levels in response to Losartan treatment. When considering only muscle pixels without T2 elevation, DyW T2 levels are significantly lower than WT (suggestive of fibrosis) whereas Losartan-treated animals do not demonstrate this decrease in muscle T2. MRI measurements suggestive of elevated inflammation and fibrosis corroborate with increased Mac-1 positive cells as well as increased Picrosirius red staining/COL1a gene expression that is returned to WT levels in response to Losartan. CONCLUSIONS: MRI is sensitive to and tightly corresponds with pathological changes in DyW mice and thus is a viable and effective non-invasive tool for assessing pathological changes. PMID- 26379185 TI - No Major Host Genetic Risk Factor Contributed to A(H1N1)2009 Influenza Severity. AB - While most patients affected by the influenza A(H1N1) pandemic experienced mild symptoms, a small fraction required hospitalization, often without concomitant factors that could explain such a severe course. We hypothesize that host genetic factors could contribute to aggravate the disease. To test this hypothesis, we compared the allele frequencies of 547,296 genome-wide single nucleotide polymorphisms (SNPs) between 49 severe and 107 mild confirmed influenza A cases, as well as against a general population sample of 549 individuals. When comparing severe vs. mild influenza A cases, only one SNP was close to the conventional p = 5*10-8. This SNP, rs28454025, sits in an intron of the GSK233 gene, which is involved in a neural development, but seems not to have any connections with immunological or inflammatory functions. Indirectly, a previous association reported with CD55 was replicated. Although sample sizes are low, we show that the statistical power in our design was sufficient to detect highly-penetrant, quasi-Mendelian genetic factors. Hence, and assuming that rs28454025 is likely to be a false positive, no major genetic factor was detected that could explain poor influenza A course. PMID- 26379186 TI - Effects of Simulated Nitrogen Deposition on Soil Respiration in a Populus euphratica Community in the Ebinur Lake Area, a Desert Ecosystem of Northwestern China. AB - One of the primary limiting factors for biological activities in desert ecosystems is nitrogen (N). This study therefore examined the effects of N and investigated the responses of an arid ecosystem to global change. We selected the typical desert plant Populus euphratica in a desert ecosystem in the Ebinur Lake area to evaluate the effects of N deposition on desert soil respiration. Three levels of N deposition (0, 37.5 and 112.5 kg.N.ha-1.yr-1) were randomly artificially provided to simulate natural N deposition. Changes in the soil respiration rates were measured from July to September in both 2010 and 2013, after N deposition in April 2010. The different levels of N deposition affected the total soil N, soil organic matter, soil C/N ratio, microorganism number, and microbial community structure and function. However, variable effects were observed over time in relation to changes in the magnitude of N deposition. Simulated high N deposition significantly reduced the soil respiration rate by approximately 23.6+/-2.5% (P<0.05), whereas low N deposition significantly increased the soil respiration rate by approximately 66.7+/-2.7% (P<0.05). These differences were clearer in the final growth stage (September). The different levels of N deposition had little effect on soil moisture, whereas N deposition significantly increased the soil temperature in the 0-5 cm layer (P<0.05). These results suggest that in the desert ecosystem of the Ebinur Lake area, N deposition indirectly changes the soil respiration rate by altering soil properties. PMID- 26379187 TI - Endothelial cell sensing, restructuring, and invasion in collagen hydrogel structures. AB - Experimental tools to model cell-tissue interactions will likely lead to new ways to both understand and treat cancer. While the mechanical properties and regulation of invasion have been recently studied for tumor cells, they have received less attention in the context of tumor vascular dynamics. In this article, we have investigated the interaction between the surfaces of structures encountered by endothelial cells invading their surrounding extracellular matrix (ECM) during angiogenesis. For this purpose, we have fabricated round and sharp geometries with various curvature and sharpness indices in collagen hydrogel over a wide range of stiffness to mimic different microenvironments varying from normal to tumor tissues. We have then cultured endothelial cells on these structures to investigate the bi-directional interaction between the cells and ECM. We have observed that cell invasion frequency is higher from the structures with the highest sharpness and curvature index, while interestingly the dependence of invasion on the local micro-geometry is strongest for the highest density matrices. Notably, structures with the highest invasion length are linked with higher deformation of side structures, which may be related to traction force-activated signaling suggesting further investigation. We have noted that round structures are more favorable for cell adhesion and in some cases round structures drive cell invasion faster than sharp ones. These results highlight the ability of endothelial cells to sense small variations in ECM geometry, and respond with a balance of matrix invasion as well as deformation, with potential implications for feedback mechanisms that may enhance vascular abnormality in response to tumor-induced ECM alterations. PMID- 26379188 TI - Patients With Burns Versus Patients With Complex Skin and Soft-Tissue Disease: An Analysis of Outcomes in the United States. AB - With the incidence of burns decreasing nationally, burn units are caring for more patients with nonburn conditions. The American Burn Association National Burn Repository does not currently report data regarding patients cared for in burn units without a diagnosis of burn. Using the National Inpatient Sample, we examined if there was a difference in characteristics and outcomes of patients admitted for burns compared with those with a primary admitting diagnosis of necrotizing skin infections and soft-tissue infections and exfoliative skin conditions. This is a retrospective study querying the National Inpatient Sample database to identify 56,102 patients from 2007 to 2012 who were admitted with a diagnosis of a burn (burn group). This group was then compared with 375,857 patients who had a primary admitting diagnosis of a necrotizing skin and/or soft tissue infection or exfoliative skin conditions (nonburn group). Clinical and demographic variables were analyzed to determine characteristics of each patient group including length of stay, disposition, complications, comorbidities, and mortality. The average age of the nonburn group was 63.7 years, whereas the average age of the burn group was 40.1 years. Overall length of stay was higher in the nonburn patients than in burn patients (10.5 vs 8.4 days, P < .001). Nonburn patients had a higher rate of medical comorbidities. Nonburn patients had higher rates of mortality (6.9% vs 2.7%) and complications. After adjusting for confounders, such as age, gender, ethnicity, and comorbidities, the nonburn group was found to have higher rates of all recorded complications. Burn patients were more likely to undergo a major operating room procedure (39.3% vs 28.1%) and routine discharge (68.4% vs 26.3%) compared with the nonburn group. Patients with necrotizing skin and soft-tissue infections and exfoliative skin conditions are older, have more comorbidities, higher complication rates, and higher mortality rates than burn patients. Given these findings, burn units may need to adjust their resource utilization, competencies, and research priorities to improve the quality of care being delivered to these two different populations. PMID- 26379189 TI - BAC transgenic mice provide evidence that p53 expression is highly regulated in vivo. AB - p53 is an important tumor suppressor and stress response mediator. Proper control of p53 level and activity is tightly associated with its function. Posttranslational modifications and the interactions with Mdm2 and Mdm4 are major mechanisms controlling p53 activity and stability. As p53 protein is short-lived and hardly detectable in unstressed situations, less is known on its basal level expression and the corresponding controlling mechanisms in vivo. In addition, it also remains obscure how p53 expression might contribute to its functional regulation. In this study, we established bacterial artificial chromosome transgenic E.coli beta-galactosidase Z gene reporter mice to monitor p53 expression in mouse tissues and identify important regulatory elements critical for the expression in vivo. We revealed preferentially high level of p53 reporter expressions in the proliferating, but not the differentiated compartments of the majority of tissues during development and tissue homeostasis. In addition, tumors as well as regenerating tissues in the p53 reporter mice also expressed high level of beta-gal. Furthermore, both the enhancer box sequence (CANNTG) in the p53 promoter and the 3' terminal untranslated region element were critical in mediating the high-level expression of the reporter. We also provided evidence that cellular myelocytomatosis oncogene was a critical player regulating p53 mRNA expression in proliferating cells and tissues. Finally, we found robust p53 activation preferentially in the proliferating compartment of mouse tissues upon DNA damage and the proliferating cells exhibited an enhanced p53 response as compared with cells in a quiescent state. Together, these results suggested a highly regulated expression pattern of p53 in the proliferating compartment controlled by both transcriptional and posttranscriptional mechanisms, and such regulated p53 expression may impose functional significance upon stress by setting up a precautionary mode in defense of cellular transformation and tumorigenesis. PMID- 26379190 TI - Bone marrow-derived mesenchymal stem cells ameliorate chronic high glucose induced beta-cell injury through modulation of autophagy. AB - Chronic hyperglycemia causes a progressive decrease of beta-cell function and mass in type 2 diabetic patients. Growing evidence suggests that augment of autophagy may be an effective approach to protect beta cells against various extra-/intracellular stimuli. In this study, we thus investigated whether bone marrow-derived mesenchymal stem cells (BM-MSCs) could ameliorate chronic high glucose (HG)-induced beta-cell injury through modulation of autophagy. Prolonged exposure to HG decreased cell viability, increased cell apoptosis and impaired basal insulin secretion and glucose-stimulated insulin secretion of INS-1 cells, but BM-MSC treatment significantly alleviated these glucotoxic alternations. In addition, western blotting displayed upregulated expression of Beclin1 and LC3-II in INS-1 cells co-cultured with BM-MSCs. Results from immunofluorescence staining and transmission electronic microscope analysis also revealed that BM-MSCs promoted autophagosomes and autolysosomes formation in HG-treated INS-1 cells. However, it should be noted that inhibition of autophagy significantly diminished the protective effects of BM-MSCs on HG-treated INS-1 cells, suggesting that the improvement of beta-cell function and survival induced by BM-MSCs was mediated through autophagy. Furthermore, our results showed that BM-MSCs improved mitochondrial function and reduced reactive oxygen species production in HG treated INS-1 cells, largely owing to autophagic clearance of impaired mitochondria. In vivo study was performed in rats with type 2 diabetes (T2D). BM MSC infusion not only ameliorated hyperglycemia, but also promoted restoration of pancreatic beta cells in T2D rats. Meanwhile, BM-MSC infusion upregulated LAMP2 expression and enhanced formation of autophagosomes and autolysosomes, combined with reduced beta-cell apoptosis and increased number of insulin granules. These findings together indicated that BM-MSCs could protect beta cells against chronic HG-induced injury through modulation of autophagy in vitro and in vivo. This study unveiled novel evidence of BM-MSCs as an ideal strategy to enhance autophagy for treatment of T2D mellitus. PMID- 26379191 TI - Inhibitory PAS domain protein is a substrate of PINK1 and Parkin and mediates cell death in a Parkinson's disease model. PMID- 26379193 TI - Smac mimetic-induced upregulation of interferon-beta sensitizes glioblastoma to temozolomide-induced cell death. AB - Inhibitor of apoptosis (IAP) proteins are frequently expressed at high levels in cancer cells and represent attractive therapeutic targets. We previously reported that the Smac (second mitochondria-derived activator of caspases) mimetic BV6, which antagonizes IAP proteins, sensitizes glioblastoma cells to temozolomide (TMZ)-induced cell death in a nuclear factor-kappaB (NF-kappaB)-dependent manner. However, BV6-induced NF-kappaB target genes responsible for this synergistic interaction have remained elusive. Using whole-genome gene expression profiling, we here identify BV6-stimulated, NF-kappaB-dependent transcriptional upregulation of interferon-beta (IFNbeta) and IFN-mediated proapoptotic signaling as critical events that mediate BV6/TMZ-induced apoptosis. Knockdown of IFNbeta significantly rescues cells from BV6/TMZ-induced cell death. Similarly, silencing of the corresponding receptor IFNalpha/beta receptor (IFNAR) confers a significant protection against apoptosis, demonstrating that IFNbeta and IFN signaling are required for BV6/TMZ-mediated cell death. Moreover, BV6 and TMZ cooperate to transcriptionally upregulate the proapoptotic B-cell lymphoma 2 family proteins Bax (Bcl-2-associated X protein) or Puma (p53-upregulated modulator of apoptosis). Knockdown of Bax or Puma significantly decreases BV6/TMZ-induced apoptosis, showing that both proteins are necessary for apoptosis. By identifying IFNbeta as a key mediator of BV6/TMZ-induced apoptosis, our study provides novel insights into the underlying molecular mechanisms of Smac mimetic-mediated chemosensitization with important implications for the development of novel treatment strategies for glioblastoma. PMID- 26379192 TI - The interplay between inflammation and metabolism in rheumatoid arthritis. AB - Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by extensive synovitis resulting in erosions of articular cartilage and marginal bone that lead to joint destruction. The autoimmune process in RA depends on the activation of immune cells, which use intracellular kinases to respond to external stimuli such as cytokines, immune complexes, and antigens. An intricate cytokine network participates in inflammation and in perpetuation of disease by positive feedback loops promoting systemic disorder. The widespread systemic effects mediated by pro-inflammatory cytokines in RA impact on metabolism and in particular in lymphocyte metabolism. Moreover, RA pathobiology seems to share some common pathways with atherosclerosis, including endothelial dysfunction that is related to underlying chronic inflammation. The extent of the metabolic changes and the types of metabolites seen may be good markers of cytokine mediated inflammatory processes in RA. Altered metabolic fingerprints may be useful in predicting the development of RA in patients with early arthritis as well as in the evaluation of the treatment response. Evidence supports the role of metabolomic analysis as a novel and nontargeted approach for identifying potential biomarkers and for improving the clinical and therapeutical management of patients with chronic inflammatory diseases. Here, we review the metabolic changes occurring in the pathogenesis of RA as well as the implication of the metabolic features in the treatment response. PMID- 26379194 TI - Drilling into RIP1 biology: what compounds are in your toolkit? PMID- 26379196 TI - Frame shift mutations of the ZMPSTE24 gene in two siblings with restrictive dermopathy. AB - Restrictive dermopathy (RD) is a rare lethal autosomal recessive genodermatosis, characterized by abnormally rigid skin with prominent superficial vasculature, erosions and epidermal hyperkeratosis, dysplastic clavicles, joint contractures, mouth fixed in the 'O' position, small pinched nose, and neonatal death. Mutations of ZMPSTE24 and LMNA genes are reported as the causes of RD, with those of ZMPSTE24 being more prevalent. Here, we report on a familial c.50delA (p.Lys17Serfs*21) mutation of the ZMPSTE24 gene, causing RD in two siblings. PMID- 26379195 TI - SGK-1 protects kidney cells against apoptosis induced by ceramide and TNF-alpha. AB - Ceramide regulates several different cellular responses including mechanisms leading to apoptosis. Serum- and glucocorticoid-inducible protein kinase (SGK)-1 is a serine threonine kinase, which activates survival pathways in response to stress stimuli. Recently, we demonstrated an anti-apoptotic role of SGK-1 in human umbilical endothelial cells treated with high glucose. In the present study, since ceramide induces apoptosis by multiple mechanisms in diabetes and its complication such as nephropathy, we aimed to investigate whether SGK-1 may protect even against apoptosis induced by ceramide in kidney cells. Human embryonic kidney (HEK)-293 cells stable transfected with SGK-1 wild type (SGK 1wt) and its dominant negative gene (SGK-1dn) have been used in this study. Apoptotic stimuli were induced by C2-ceramide and TNF-alpha to increase endogenous synthesis of ceramide. Upon activation with these stimuli, SGK-1wt transfected cells have a statistically significant reduction of apoptosis compared with SGK-1dn cells (P<0.001). This protection was dependent on activation of caspase-3 and Poly-ADP-ribose-polymerase-1 (PARP-1) cleavage. SGK-1 and AKT-1 two highly homologous kinases differently reacted to ceramide treatment, since SGK-1 increases in response to apoptotic stimulus while AKT-1 decreases. This enhancement of SGK-1 was dependent on p38-mitogen-activated protein kinases (p38MAPK), cyclic-adenosine-monophosphate/protein kinase A (cAMP/PKA) and phosphoinositide-3-kinase (PI3K) pathways. Especially, by using selective LY294002 inhibitor, we demonstrated that the most involved pathway in the SGK-1 mediated process of protection was PI3K. Treatment with inhibitor of SGK-1 (GSK650394) significantly enhanced TNF-alpha-dependent apoptosis in HEK-293 cells overexpressing SGK-1wt. Caspase-3, -8 and -9 selective inhibitors confirmed that SGK-1 reduced the activation of caspase-dependent apoptosis, probably by both intrinsic and extrinsic pathways. In conclusion, we demonstrated that in kidney cells, overexpression of SGK-1 is protective against ceramide-induced apoptosis and the role of SGK-1 can be potentially explored as a therapeutic target in conditions like diabetes, where ceramide levels are increased. PMID- 26379197 TI - Nuclear autonomy in multinucleate fungi. AB - Within many fungal syncytia, nuclei behave independently despite sharing a common cytoplasm. Creation of independent nuclear zones of control in one cell is paradoxical considering random protein synthesis sites, predicted rapid diffusion rates, and well-mixed cytosol. In studying the surprising fungal nuclear autonomy, new principles of cellular organization are emerging. We discuss the current understanding of nuclear autonomy, focusing on asynchronous cell cycle progression where most work has been directed. Mechanisms underlying nuclear autonomy are diverse including mRNA localization, ploidy variability, and nuclear spacing control. With the challenges fungal syncytia face due to cytoplasmic size and shape, they serve as powerful models for uncovering new subcellular organization modes, variability sources among isogenic uninucleate cells, and the evolution of multicellularity. PMID- 26379198 TI - Staining with 0.05% neutral red reduces nutrient uptake by wheat roots. AB - A number of studies have used a 0.05% solution of neutral red to stain live roots so that short term root growth could be measured. These studies, which used a 5 or 10 min staining time, report no effects of the stain on plant properties such as growth, respiration, or nitrate uptake. This paper reports on two experiments conducted to determine whether this staining technique, with a 15 min stain time, affected macronutrient uptake of 6- and 7-week-old wheat (Triticum aestivum L.) plants grown in solution culture. The results showed that, compared with unstained controls, staining plants with 0.05% neutral red halted or halved nitrate uptake measured over a 4 h period the following day. Potassium uptake was also significantly reduced by staining. In the experiment with smaller plants nutrient uptake rate recovered 5 days after staining, but not in the second experiment with larger plants. Stained roots were 19% narrower than unstained roots, suggesting that the stain affected the root structure. We do not recommend the use of 0.05% neutral red staining, for wheat at least, in experiments where accurate measurement of nutrient uptake rate is important. PMID- 26379199 TI - Foliar application of methyl jasmonate induced physio-hormonal changes in Pisum sativum under diverse temperature regimes. AB - Global climate change brings with it unwarranted shifts in both abiotic (heat stress, cold stress, wind, precipitation) and biotic (pathogens, pests) environmental factors, thus posing a threat to agricultural productivity across the world. In plants, lodging due to storms or herbivory causes wounding stress and consequently enhances endogenous jasmonates. In response, the plant growth is arrested as plant defense is prioritized. We pre-treated pea plants with elevated methyl jasmonate (MeJA) levels i.e. 50 MUM, 100 MUM and 200 MUM under controlled growth chamber conditions. The pre-treated plants were then kept at 40 degrees C (heat stress--HS), 4 degrees C (cold stress--CS) and 20 degrees C (optimum/control temperature--OT) for 72 h. The effect of such treatments on plant growth attributes, photosynthesis, stomatal conductance, cell death rate, and regulation of endogenous hormones were observed. Elevated MeJA application hindered plant growth attributes under HS, CS and OT conditions. Moreover, elevated MeJA levels lowered the rate of photosynthesis and stomatal conductance, induced stomatal closure, caused higher cells mortality in leaves under HS, CS, and OT conditions. Endogenous ABA contents significantly declined in all MeJA treatments under HS and OT, but increased under CS conditions. Exogenous MeJA enhanced endogenous jasmonic acid contents of pea plants, but altered endogenous salicylic acid contents under varying temperatures. Current study shows that higher concentrations of exogenous MeJA strengthen plant defense mechanism by hindering plant growth under stress conditions. PMID- 26379200 TI - Ecological risks of home and personal care products in the riverine environment of a rural region in South China without domestic wastewater treatment facilities. AB - Home and personal care products (HPCPs) including biocides, benzotriazoles (BTs) and ultraviolet (UV) filters are widely used in our daily life. After use, they are discharged with domestic wastewater into the receiving environment. This study investigated the occurrence of 29 representative HPCPs, including biocides, BTs and UV filters, in the riverine environment of a rural region of South China where no wastewater treatment plants were present, and assessed their potential ecological risks to aquatic organisms. The results showed the detection of 11 biocides and 4 BTs in surface water, and 9 biocides, 3 BTs and 4 UV filters in sediment. In surface water, methylparaben (MeP), triclocarban (TCC), and triclosan (TCS) were detected at all sites with median concentrations of 9.23 ng/L, 2.64 ng/L and 5.39 ng/L, respectively. However, the highest median concentrations were found for clotrimazole (CLOT), 5-methyl-1H-benzotriazole (MBT) and carbendazim (CARB) at 55.6 ng/L, 33.7 ng/L and 13.8 ng/L, respectively. In sediment, TCC, TCS, and UV-326 were detected with their maximum concentrations up to 353 ng/g, 155 ng/g, and 133 ng/g, respectively. The concentrations for those detected HPCPs in surface water and sediment were generally lower in the upper reach (rural area) of Sha River than in the lower reach of Sha River with close proximity to Dongjiang River (Pt-test<0.05), indicating other input sources of HPCPs in the lower reach. Biocides showed significantly higher levels in surface water in the wet season than in the dry and intermediate seasons. Preliminary risk assessment demonstrated that the majority of HPCPs monitored represented low risk in surface waters. There are potentially greater risks to aquatic organisms from the use of TCS and TCC in the wet season than in dry and intermediate seasons in surface waters. This preliminary assessment also indicates potential concerns associated with TCC, TCS, DEET, CARB, and CLOT in sediments, although additional data should be generated to assess this fully. Thus future research is needed to investigate ecological effects of these HPCPs on benthic organisms in sediment of rural rivers receiving untreated wastewater discharge. PMID- 26379201 TI - Combination effects of pyrethroids and neonicotinoids on development and survival of Chironomus riparius. AB - Standard ecotoxicological risk assessments are conducted on individual substances, however monitoring of streams in agricultural areas has shown that pesticides are rarely present alone. In fact, brief but intense pulse events such as storm water runoff and spray drift during application subject freshwater environments to complex mixtures of pesticides at high concentrations. This study investigates the potential risks to non-target aquatic organisms exposed to a brief but intense mixture of the neonicotinoid pesticides imidacloprid and thiacloprid and the pyrethroid pesticides deltamethrin and esfenvalerate, compared to single substance exposure. All four of these pesticides have been detected in surface waters at concentrations higher than benchmark values and both classes of pesticides are known to exert adverse effects on non-target aquatic organisms under single substance exposure scenarios. First instar midge larvae of the non-target aquatic organism, Chironomus riparius, were exposed to combinations of these four pesticides at 50% of their LC50 (96 h) values in a 1h pulse. They were then reared to adulthood in uncontaminated conditions and assessed for survival, development time and fecundity. Our results show that the risk of disruption to survival and development of non-target aquatic organisms under this scenario is not negligible on account of the significant increases in mortality of C. riparius found in the majority of the pesticide exposures and the delays in development after pyrethroid exposure. While none of the deleterious effects appear to be amplified by combination of the pesticides, there is some evidence for antagonism. No effects on fecundity by any of the pesticide treatments were observed. PMID- 26379202 TI - Wastewater compounds in urban shallow groundwater wells correspond to exfiltration probabilities of nearby sewers. AB - Wastewater compounds are frequently detected in urban shallow groundwater. Sources include sewage or reclaimed wastewater, but origins are often unknown. In a prior study, wastewater compounds were quantified in waters sampled from shallow groundwater wells in a small coastal California city. Here, we resampled those wells and expanded sample analyses to include sewage- or reclaimed water specific indicators, i.e. pharmaceutical and personal care product chemicals or disinfection byproducts. Also, we developed a geographic information system (GIS) based model of sanitary sewer exfiltration probability--combining a published pipe failure model accounting for sewer pipe size, age, materials of construction, with interpolated depths to groundwater--to determine if sewer system attributes relate to wastewater compounds in urban shallow groundwater. Across the wells, groundwater samples contained varying wastewater compounds, including acesulfame, sucralose, bisphenol A, 4-tert-octylphenol, estrone and perfluorobutanesulfonic acid (PFBS). Fecal indicator bacterial concentrations and toxicological bioactivities were less than known benchmarks. However, the reclaimed water in this study was positive for all bioactivity tested. Excluding one well intruded by seawater, the similarity of groundwater to sewage, based on multiple indicators, increased with increasing sanitary sewer exfiltration probability (modeled from infrastructure within ca. 300 m of each well). In the absence of direct exfiltration or defect measurements, sewer exfiltration probabilities modeled from the collection system's physical data can indicate potential locations where urban shallow groundwater is contaminated by sewage. PMID- 26379203 TI - Reaction of bromine and chlorine with phenolic compounds and natural organic matter extracts--Electrophilic aromatic substitution and oxidation. AB - Phenolic compounds are known structural moieties of natural organic matter (NOM), and their reactivity is a key parameter for understanding the reactivity of NOM and the disinfection by-product formation during oxidative water treatment. In this study, species-specific and/or apparent second order rate constants and mechanisms for the reactions of bromine and chlorine have been determined for various phenolic compounds (phenol, resorcinol, catechol, hydroquinone, phloroglucinol, bisphenol A, p-hydroxybenzoic acid, gallic acid, hesperetin and tannic acid) and flavone. The reactivity of bromine with phenolic compounds is very high, with apparent second order rate constants at pH 7 in the range of 10(4) to 10(7) M(-1) s(-1). The highest value was recorded for the reaction between HOBr and the fully deprotonated resorcinol (k = 2.1 * 10(9) M(-1) s(-1)). The reactivity of phenolic compounds is enhanced by the activating character of the phenolic substituents, e.g. further hydroxyl groups. With the data set from this study, the ratio between the species-specific rate constants for the reactions of chlorine versus bromine with phenolic compounds was confirmed to be about 3000. Phenolic compounds react with bromine or chlorine either by oxidation (electron transfer, ET) or electrophilic aromatic substitution (EAS) processes. The dominant process mainly depends on the relative position of the hydroxyl substituents and the possibility of quinone formation. While phenol, p hydroxybenzoic acid and bisphenol A undergo EAS, hydroquinone, catechol, gallic acid and tannic acid, with hydroxyl substituents in ortho or para positions, react with bromine by ET leading to quantitative formation of the corresponding quinones. Some compounds (e.g. phloroglucinol) show both partial oxidation and partial electrophilic aromatic substitution and the ratio observed for the pathways depends on the pH. For the reaction of six NOM extracts with bromine, electrophilic aromatic substitution accounted for only 20% of the reaction, and for one NOM extract (Pony Lake fulvic acid) it accounted for <10%. This shows that for natural organic matter samples, oxidation (ET) is far more important than bromine incorporation (EAS). PMID- 26379204 TI - Evaluation of sustainable electron donors for nitrate removal in different water media. AB - An external electron donor is usually included in wastewater and groundwater treatment systems to enhance nitrate removal through denitrification. The choice of electron donor is critical for both satisfactory denitrification rates and sustainable long-term performance. Electron donors that are waste products are preferred to pure organic chemicals. Different electron donors have been used to treat different water types and little is known as to whether there are any electron donors that are suitable for multiple applications. Seven different carbon rich waste products, including liquid and solid electron donors, were studied in comparison to pure acetate. Batch-scale tests were used to measure their ability to reduce nitrate concentrations in a pure nutrient solution, light greywater, secondary-treated wastewater and tertiary-treated wastewater. The tested electron donors removed oxidised nitrogen (NOx) at varying rates, ranging from 48 mg N/L/d (acetate) to 0.3 mg N/L/d (hardwood). The concentrations of transient nitrite accumulation also varied across the electron donors. The different water types had an influence on NOx removal rates, the extent of which was dependent on the type of electron donor. Overall, the highest rates were recorded in light greywater, followed by the pure nutrient solution and the two partially treated wastewaters. Cotton wool and rice hulls were found to be promising electron donors with good NOx removal rates, lower leachable nutrients and had the least variation in performance across water types. PMID- 26379205 TI - Euler-Lagrange CFD modelling of unconfined gas mixing in anaerobic digestion. AB - A novel Euler-Lagrangian (EL) computational fluid dynamics (CFD) finite volume based model to simulate the gas mixing of sludge for anaerobic digestion is developed and described. Fluid motion is driven by momentum transfer from bubbles to liquid. Model validation is undertaken by assessing the flow field in a labscale model with particle image velocimetry (PIV). Conclusions are drawn about the upscaling and applicability of the model to full-scale problems, and recommendations are given for optimum application. PMID- 26379206 TI - The anococcygeal ligaments: Cadaveric study with application to our understanding of incontinence in the elderly. AB - The term "anococcygeal ligament (ACL)" has been used to refer to two distinct structures: a superficial fibrous band originating from the myosepta of the external anal sphincter (EAS) and running upwards to the coccyx (the superficial ACL); and a deep fibrous band originating from the periosteum of the coccyx, merging with the thick presacral fascia and attaching to the superior end of the EAS (the deep ACL). In the present work, elastic fiber histology and muscle immunohistochemistry of sagittal sections obtained from 15 donated elderly male cadavers showed that superficial ACL, corresponding to a superficial fascia or skin ligament, was composed of very tortuous elastic fibers, with a fine elastic fiber mesh at their coccygeal attachment; whereas the deep ACL was composed of almost straight collagen and elastic fibers, intermingled with the coccygeal periosteum. Due to the weak insertion into the coccyx and the wavy course, the superficial ACL is unlikely to provide, even in association with contraction of the longitudinal anal muscle, a stable mechanical support to maintain the configuration of the EAS. Being similar to the suspensory ligament of breast, tissue repair of the skin ligament would not have a mechanical role. In contrast, the deep ACL, in association with the thick presacral fascia, likely plays a role in maintaining a suitable positioning of the anorectum to the coccyx. However, their relative lack of smooth muscles compared with rich elastic fibers indicates that both ACLs may become permanently overextended under conditions of long-term mechanical stress. PMID- 26379207 TI - Aldoxorubicin in Sarcoma: Teaching an Old Drug New Tricks. PMID- 26379208 TI - Role of endocannabinoids in the progression of diabetic retinopathy. AB - In the past decades, the role of numerous factors in the pathophysiology of diabetic retinopathy has been explored, following which marked progress has been made in developing several novel therapeutic options, such as anti-vascular endothelial growth factor, anti-tumor necrosis factor-alpha and various other anti-inflammatory and anti-angiogenic agents, for the treatment of diabetic retinopathy. However, the involvement of endocannabinoid system in its pathogenesis has not been much explored. This review aims at unveiling every aspect of association of the endocannabinoid system and its interactions with various physiological and pathological pathways to induce disease progression. The various alterations induced by endocannabinoids, such as anandamide and 2 arachidonylglycerol, in retina during hyperglycaemia clearly demonstrate and verify their involvement in aggravating the pathological conditions, hence leading to the progression of diabetic retinopathy. Exploring this involvement furthermore, in greater depths, might be beneficial in acknowledging and understanding the hidden aspects of the pathogenesis of this complication even better and might provide a therapeutically beneficial alternative target to combat and restrict its progression amongst diabetic patients. PMID- 26379209 TI - Extent of Exacerbation of Chronic Health Conditions by Visual Impairment in Terms of Health-Related Quality of Life. AB - IMPORTANCE: Visual impairment (VI) causes a considerable public health burden and substantial deterioration in health-related quality of life (HRQoL). However, the relative effect of VI on HRQoL compared with other chronic health conditions is unknown as is the additive effect of VI with other conditions. OBJECTIVE: To investigate whether the impact of chronic health conditions on HRQoL varies according to VI presence. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study involving 29,639 participants aged 19 years and older and using a multistage, probability-cluster survey, which can produce nationally representative estimates. We analyzed data from the 2008-2012 Korean National Health and Nutrition Examination Survey, which included results for vision assessment and HRQoL, measured using the European Quality of Life-5 Dimensions Questionnaire (EQ-5D). All analyses were conducted in October and November 2014. Visual impairment was defined as the presenting distance best-corrected visual acuity of less than decimal 0.32 (approximate Snellen equivalent 20/63). Linear regression models accounting for sample weights were used to examine interactions between VI and each of 14 chronic health conditions on the EQ-5D index score, adjusted for demographic and socioeconomic covariates. MAIN OUTCOMES AND MEASURES: The EQ-5D index score for participants with VI or 14 chronic health conditions, as well as the effect of the interactions between VI and each condition on the EQ-5D index score. RESULTS: The EQ-5D index score with VI was substantially lower than without VI (mean difference, -0.158; 95% CI, -0.186 to 0.130; P < .001). In most conditions, the comorbidity with VI resulted in lower EQ-5D index scores; furthermore, participants with stroke, osteoarthritis or rheumatic arthritis, hepatitis B or C, and depression showed lower EQ-5D index scores than expected when they were comorbid with VI, indicating an interaction between VI and each condition. The estimated beta coefficients for interaction terms were -0.256 (95% CI, -0.480 to -0.032) for stroke, -0.124 (95% CI, -0.223 to -0.026) for osteoarthritis or rheumatic arthritis, -0.183 (95% CI, -0.327 to 0.038) for hepatitis B or C, and -0.130 (95% CI, -0.229 to -0.032) for depression. CONCLUSIONS AND RELEVANCE: These results suggest that VI has a substantial effect on HRQoL, even in the presence of concurrent chronic health conditions, and the combined effect of VI and stroke, osteoarthritis/rheumatic arthritis, hepatitis, or depression on HRQoL was greater. However, because this study group was a representative sampling of South Koreans, generalization to other races/ethnicities and countries should be approached with caution. PMID- 26379210 TI - Somatosensory mu activity reflects imagined pain intensity of others. AB - In accordance with simulation theories of empathy, the somatosensory cortex is involved in the perception of pain of others. Cognitive processes, like perspective taking, can alter empathy-related activity within the somatosensory cortex. The current study investigates whether this modulation is caused by the imagined sensation of pain or by the cognitive load of a perspective-taking task. Applying a within-subject design, participants (N = 30) watched pictures of painful and nonpainful actions, while imagining reduced, normal, or increased pain perception of the observed individual. Mu activity (8-13 Hz), which is inversely correlated with sensorimotor-cortex activity, was measured via EEG. To calculate mu activity (central electrodes) and alpha activity (occipital electrodes), which served as a control for effects of cognitive load, a fast Fourier transform was applied. Mu suppression linearly increased from reduced to normal to increased imagined pain (p < .05), while alpha activity was unaffected by the imagined pain (p > .80). Suppression of the 8-13 Hz band at central and occipital electrodes was stronger in response to painful actions compared to nonpainful actions (p < .01). These results indicate that modulation of mu activity through perspective taking reflects the imagined pain intensity and not the cognitive load induced by the task. PMID- 26379211 TI - A simple and high-resolution HPLC-PDA method for simultaneous quantification of local anesthetics in in vitro buccal permeation enhancement studies. AB - A simple, isocratic, high-resolution and prompt HPLC-PDA method was developed and validated for the simultaneous quantification of prilocaine (PCL) and lidocaine (LCL) hydrochlorides in in vitro buccal iontophoresis-driven permeation studies. A reversed-phase C18 column (250 mm x 4.6 mm, 3MUm, 110A) was used for the chromatographic separation. The mobile phase contained acetonitrile: 0.1M sodium phosphate buffer, pH 7.0 (1:1, v/v), plus 0.05% (v/v) diethylamine. The isocratic flow rate was set at 1 mL/min and the detection wavelength was 203 nm. PCL and LCL eluted in 8.9 min and 13 min, respectively, and the system suitability parameters varied within an acceptable range. The method was selective, sensitive, precise, accurate and robust, producing a linear plot at the concentration range of 0.25 to 10 ug/mL. The application of this method was demonstrated by a significant enhancement of the permeation of PCL and LCL with the application of iontophoresis (1 mA/cm(2) per 1 h) through isolated porcine esophageal epithelium. The amount of the drug retained in the epithelium also increased with the application of an electrical current. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26379214 TI - Error in Byline. PMID- 26379215 TI - Surfactant-Free Emulsion-Based Preparation of Redox-Responsive Nanogels. AB - A surfactant-free emulsion-based approach is developed for preparation of nanogels. A water-in-oil emulsion is generated feasibly from a mixture of water and a solution of disulfide-containing hyperbranched PEGylated poly(amido amine)s, poly(BAC2-AMPD1)-PEG, in chloroform. The water droplets in the emulsion are stabilized and filled with poly(BAC2-AMPD1)-PEG, and the crosslinked poly(amido amine)s nanogels are formed via the intermolecular disulfide exchange reaction. FITC-dextran is loaded within the nanogels by dissolving the compound in water before emulsification. Transmission electron microscopy and dynamic light scattering are applied to characterize the emulsion and the nanogels. The effects of the homogenization rate and the ratio of water/polymer are investigated. Redox-induced degradation and FITC-dextran release profile of the nanogels are monitored, and the results show efficient loading and redox responsive release of FITC-dextran. This is a promising approach for the preparation of nanogels for drug delivery, especially for neutral charged carbohydrate-based drugs. PMID- 26379216 TI - Validation of the four-dimensional symptom questionnaire (4DSQ) and prevalence of psychological symptoms in orthopedic shoulder patients. AB - Psychological problems are common in shoulder patients. A validated psychological questionnaire measuring clinically relevant psychological symptoms (including distress, depression, anxiety, and somatization) in shoulder patients is lacking. The Four-Dimensional Symptom Questionnaire (4DSQ) is a self-report questionnaire to identify distress, depression, anxiety, and somatization which has been validated in primary care populations. The aim of this study was to validate the 4DSQ in orthopedic shoulder patients. We assessed whether the 4DSQ measures these four constructs the same way in an orthopedic population with shoulder problems compared to a general practice population. We also investigated the prevalence of psychological symptoms in shoulder patients. The shoulder group consisted of 200 consecutive patients and the general practice group comprised 368 patients, matched for gender and age. Differential item functioning analysis showed that the 4DSQ measures the different psychological symptoms in orthopedic shoulder patients the same way as in general practice patients. The shoulder patients tended to score higher on the somatization scale, resulting in a new cut-off point for somatization. The prevalence of distress, somatization, anxiety, and depression in the shoulder group was 23%, 14%, 10%, and 8%, respectively. It can be concluded from this study that the 4DSQ in orthopedic shoulder patients measures the same constructs as in general practice patients and can therefore be used in orthopedic practice to measure psychological symptoms in patients with shoulder complaints. PMID- 26379220 TI - Calcite single crystals as hosts for atomic-scale entrapment and slow release of drugs. PMID- 26379225 TI - Alterations of the Plasma Peptidome Profiling in Colorectal Cancer Progression. AB - Early detection of colorectal cancer (CRC) remains a challenge. It has been highlighted that the pathological alterations within an organ and tissues might be reflected in serum or plasma proteomic/peptidic patterns. The aim of the study was to follow the changes in the plasma peptides associated to colorectal cancer progression by mass spectrometry. This study included 27 adenoma, 67 CRC (n = 33 I-II stage and n = 34 III-IV stage), 23 liver metastasis from CRC patients and 34 subjects disease-free as controls. For plasma peptides analysis, samples purification was performed on the Nanoporous Silica Chips technology followed by matrix-assisted laser desorption/ionisation-time of flight analysis. Since the high complexity of the obtained dataset, multivariate statistical analysis, and discriminant pattern recognition were performed for study groups classification. Forty-four of 88 ionic species were successfully identified as fragments of peptides and proteins physiologically circulating in the blood and belonging to immune and coagulation systems and inflammatory mediators. Many peptides clustered into sets of overlapping sequences with ladder-like truncation clearly associated to proteolytic processes of both endo- and exoproteases activity. Comparing to controls, a different median ion intensity of the group-type fragments distribution was observed. Moreover, the degradation pattern obtained by proteolytic cleavage was different into study groups. This pattern was specific and characteristic of each group: controls, colon tumour disease (including adenoma and CRC), and liver metastasis, revealing a role as biomarker in early diagnosis and prognosis. Our findings highlighted peculiar changes in protease activity characteristic of CRC progression from pre-cancer lesion to metastatic disease. J. Cell. Physiol. 231: 915-925, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26379222 TI - Harnessing the multifunctionality in nature: a bioactive agent release system with self-antimicrobial and immunomodulatory properties. AB - Major problems with biomedical devices in particular implants located in nonsterile environments concern: (i) excessive immune response to the implant, (ii) development of bacterial biofilms, and (iii) yeast and fungi infections. An original multifunctional coating that addresses all these issues concomitantly is developed. A new exponentially growing polyelectrolyte multilayer film based on polyarginine (PAR) and hyaluronic acid (HA) is designed. The films have a strong inhibitory effect on the production of inflammatory cytokines released by human primary macrophage subpopulations. This could reduce potential chronic inflammatory reaction following implantation. Next, it is shown that PAR, due to its positive charges, has an antimicrobial activity in film format against Staphylococcus aureus for 24 h. In order to have a long-term antimicrobial activity, a precursor nanoscale silver coating is deposited on the surface before adding the PAR/HA films. Moreover, the PAR/HA films can be easily further functionalized by embedding antimicrobial peptides, like catestatin (CAT), a natural host defense peptide. This PAR/HA+CAT film proves to be effective as an antimicrobial coating against yeast and fungi and its cytocompatibility is also assessed. Finally, this all-in-one system constitutes an original strategy to limit inflammation and prevents bacteria, yeast, and fungi infections. PMID- 26379226 TI - Rapid Progression of Necrotic Lesion of the Mandibular Gingiva in a Pancytopenic Patient. Invasive necrotizing fungal gingivitis. PMID- 26379227 TI - Understanding public perceptions of risk regarding outdoor pet cats to inform conservation action. AB - Free-ranging domestic cats (Felis catus) incur and impose risks on ecosystems and represent a complex issue of critical importance to biodiversity conservation and cat and human health globally. Prior social science research on this topic is limited and has emphasized feral cats even though owned cats often comprise a large proportion of the outdoor cat population, particularly in urban areas. To address this gap, we examined public risk perceptions and attitudes toward outdoor pet cats across varying levels of urbanization, including along the wildland-urban interface, in Colorado (U.S.A.), through a mail survey of 1397 residents. Residents did not view all types of risks uniformly. They viewed risks of cat predation on wildlife and carnivore predation on cats as more likely than disease-related risks. Additionally, risk perceptions were related to attitudes, prior experiences with cats and cat-wildlife interactions, and cat-owner behavior. Our findings suggest that changes in risk perceptions may result in behavior change. Therefore, knowledge of cat-related risk perceptions and attitudes could be used to develop communication programs aimed at promoting risk aversive behaviors among cat owners and cat-management strategies that are acceptable to the public and that directly advance the conservation of native species. PMID- 26379228 TI - MicroRNA-based conversion of human fibroblasts into striatal medium spiny neurons. AB - The ability to generate human neurons of specific subtypes of clinical importance offers experimental platforms that may be instrumental for disease modeling. We recently published a study demonstrating the use of neuronal microRNAs (miRNAs) and transcription factors to directly convert human fibroblasts to a highly enriched population of striatal medium spiny neurons (MSNs), a neuronal subpopulation that has a crucial role in motor control and harbors selective susceptibility to cell death in Huntington's disease. Here we describe a stepwise protocol for the generation of MSNs by direct neuronal conversion of human fibroblasts in 30 d. We provide descriptions of cellular behaviors during reprogramming and crucial steps involved in gene delivery, cell adhesion and culturing conditions that promote cell survival. Our protocol offers a unique approach to combine microRNAs and transcription factors to guide the neuronal conversion of human fibroblasts toward a specific neuronal subtype. PMID- 26379229 TI - Genomic variant annotation and prioritization with ANNOVAR and wANNOVAR. AB - Recent developments in sequencing techniques have enabled rapid and high throughput generation of sequence data, democratizing the ability to compile information on large amounts of genetic variations in individual laboratories. However, there is a growing gap between the generation of raw sequencing data and the extraction of meaningful biological information. Here, we describe a protocol to use the ANNOVAR (ANNOtate VARiation) software to facilitate fast and easy variant annotations, including gene-based, region-based and filter-based annotations on a variant call format (VCF) file generated from human genomes. We further describe a protocol for gene-based annotation of a newly sequenced nonhuman species. Finally, we describe how to use a user-friendly and easily accessible web server called wANNOVAR to prioritize candidate genes for a Mendelian disease. The variant annotation protocols take 5-30 min of computer time, depending on the size of the variant file, and 5-10 min of hands-on time. In summary, through the command-line tool and the web server, these protocols provide a convenient means to analyze genetic variants generated in humans and other species. PMID- 26379230 TI - Thermal proteome profiling for unbiased identification of direct and indirect drug targets using multiplexed quantitative mass spectrometry. AB - The direct detection of drug-protein interactions in living cells is a major challenge in drug discovery research. Recently, we introduced an approach termed thermal proteome profiling (TPP), which enables the monitoring of changes in protein thermal stability across the proteome using quantitative mass spectrometry. We determined the intracellular thermal profiles for up to 7,000 proteins, and by comparing profiles derived from cultured mammalian cells in the presence or absence of a drug we showed that it was possible to identify direct and indirect targets of drugs in living cells in an unbiased manner. Here we demonstrate the complete workflow using the histone deacetylase inhibitor panobinostat. The key to this approach is the use of isobaric tandem mass tag 10 plex (TMT10) reagents to label digested protein samples corresponding to each temperature point in the melting curve so that the samples can be analyzed by multiplexed quantitative mass spectrometry. Important steps in the bioinformatic analysis include data normalization, melting curve fitting and statistical significance determination of compound concentration-dependent changes in protein stability. All analysis tools are made freely available as R and Python packages. The workflow can be completed in 2 weeks. PMID- 26379231 TI - Birth Preparedness and Complication Readiness among Pregnant Women in Duguna Fango District, Wolayta Zone, Ethiopia. AB - BACKGROUND: Birth Preparedness and Complication Readiness is a strategy to promote the timely use of skilled maternal and neonatal care, especially during childbirth, based on the theory that preparing for childbirth and being ready for complications reduces delays in obtaining this care. OBJECTIVE: This study was conducted to assess birth preparedness and complication readiness and its associated factors among pregnant woman in Duguna Fango District in Wolayta Zone, South Ethiopia. METHODS: A community based cross-sectional study was conducted in 2013, on a sample of 578 pregnant women. Data were collected using pre-tested and structured questionnaire. The collected data were analyzed by SPSS for windows version 16.0. The women were asked whether they followed the desired five steps while pregnant: identified a trained birth attendant, identified a health facility, arranged for transport, identified blood donor and saved money for emergency. Taking at least three steps was considered being well-prepared. RESULTS: Among 578 pregnant women only one tenth (10.7%) of pregnant women identified skilled provider. Only 103 (18.1%) arranged transportation to health facility. Two hundred forty eight (43.6%) identified health facility for delivery and/or for obstetric emergencies. more than half (54.1%) of families saved money for incurred costs of delivery and emergency if needed. only few 17(3%) identified potential blood donor in case of emergency. Two hundred sixty four (46.4%) of the respondents reported that they intended to deliver at home, and more than half (53.6) planned to deliver at health facilities. Overall less than one fifth 18.3% of pregnant women were well prepared. The adjusted multivariate model showed that significant predictors for being well-prepared were maternal availing of antenatal services (AOR = 2.95, 95% CI: 1.62-5.37), being pregnant for the first time (AOR = 3.37, 95% CI: 1.45-7.82), having knowledge of at least two danger signs during pregnancy (AOR = 2.81, 95% CI: 1.69-4.67) and history of past obstetric complication (AOR = 2.98, 95% CI: 1.35-6.58). CONCLUSION: Birth preparedness practice in the study area was found to be low. Information, Education and Communication (IEC) on birth preparedness and complication readiness for young people should start early adolescence. The government officials and partners that are working in areas of maternal health should come up with strategies to improve birth preparedness at individual and community level. PMID- 26379232 TI - EEGNET: An Open Source Tool for Analyzing and Visualizing M/EEG Connectome. AB - The brain is a large-scale complex network often referred to as the "connectome". Exploring the dynamic behavior of the connectome is a challenging issue as both excellent time and space resolution is required. In this context Magneto/Electroencephalography (M/EEG) are effective neuroimaging techniques allowing for analysis of the dynamics of functional brain networks at scalp level and/or at reconstructed sources. However, a tool that can cover all the processing steps of identifying brain networks from M/EEG data is still missing. In this paper, we report a novel software package, called EEGNET, running under MATLAB (Math works, inc), and allowing for analysis and visualization of functional brain networks from M/EEG recordings. EEGNET is developed to analyze networks either at the level of scalp electrodes or at the level of reconstructed cortical sources. It includes i) Basic steps in preprocessing M/EEG signals, ii) the solution of the inverse problem to localize / reconstruct the cortical sources, iii) the computation of functional connectivity among signals collected at surface electrodes or/and time courses of reconstructed sources and iv) the computation of the network measures based on graph theory analysis. EEGNET is the unique tool that combines the M/EEG functional connectivity analysis and the computation of network measures derived from the graph theory. The first version of EEGNET is easy to use, flexible and user friendly. EEGNET is an open source tool and can be freely downloaded from this webpage: https://sites.google.com/site/eegnetworks/. PMID- 26379233 TI - Reliability and Validity of Selected PROMIS Measures in People with Rheumatoid Arthritis. AB - PURPOSE: To evaluate the reliability and validity of 11 PROMIS measures to assess symptoms and impacts identified as important by people with rheumatoid arthritis (RA). METHODS: Consecutive patients (N = 177) in an observational study completed PROMIS computer adapted tests (CATs) and a short form (SF) assessing pain, fatigue, physical function, mood, sleep, and participation. We assessed test-test reliability and internal consistency using correlation and Cronbach's alpha. We assessed convergent validity by examining Pearson correlations between PROMIS measures and existing measures of similar domains and known groups validity by comparing scores across disease activity levels using ANOVA. RESULTS: Participants were mostly female (82%) and white (83%) with mean (SD) age of 56 (13) years; 24% had <= high school, 29% had RA <= 5 years with 13% <= 2 years, and 22% were disabled. PROMIS Physical Function, Pain Interference and Fatigue instruments correlated moderately to strongly (rho's >= 0.68) with corresponding PROs. Test-retest reliability ranged from .725-.883, and Cronbach's alpha from .906-.991. A dose-response relationship with disease activity was evident in Physical Function with similar trends in other scales except Anger. CONCLUSIONS: These data provide preliminary evidence of reliability and construct validity of PROMIS CATs to assess RA symptoms and impacts, and feasibility of use in clinical care. PROMIS instruments captured the experiences of RA patients across the broad continuum of RA symptoms and function, especially at low disease activity levels. Future research is needed to evaluate performance in relevant subgroups, assess responsiveness and identify clinically meaningful changes. PMID- 26379235 TI - A Call for Incorporating Social Research in the Global Struggle against Snakebite. PMID- 26379234 TI - A Multi-Marker Genetic Association Test Based on the Rasch Model Applied to Alzheimer's Disease. AB - Results from Genome-Wide Association Studies (GWAS) have shown that the genetic basis of complex traits often include many genetic variants with small to moderate effects whose identification remains a challenging problem. In this context multi-marker analysis at the gene and pathway level can complement traditional point-wise approaches that treat the genetic markers individually. In this paper we propose a novel statistical approach for multi-marker analysis based on the Rasch model. The method summarizes the categorical genotypes of SNPs by a generalized logistic function into a genetic score that can be used for association analysis. Through different sets of simulations, the false-positive rate and power of the proposed approach are compared to a set of existing methods, and shows good performances. The application of the Rasch model on Alzheimer's Disease (AD) ADNI GWAS dataset also allows a coherent interpretation of the results. Our analysis supports the idea that APOE is a major susceptibility gene for AD. In the top genes selected by proposed method, several could be functionally linked to AD. In particular, a pathway analysis of these genes also highlights the metabolism of cholesterol, that is known to play a key role in AD pathogenesis. Interestingly, many of these top genes can be integrated in a hypothetic signalling network. PMID- 26379237 TI - Inter-Tributary Movements by Resident Salmonids across a Boreal Riverscape. AB - Stream-dwelling fishes inhabit river networks where resources are distributed heterogeneously across space and time. Current theory emphasizes that fishes often perform large-scale movements among habitat patches for reproduction and seeking refugia, but assumes that fish are relatively sedentary during growth phases of their life cycle. Using stationary passive integrated transponder (PIT) tag antennas and snorkel surveys, we assessed the individual and population level movement patterns of two species of fish across a network of tributaries within the Wood River basin in southwestern Alaska where summer foraging opportunities vary substantially among streams, seasons, and years. Across two years, Arctic grayling (Thymallus arcticus) and rainbow trout (Oncorhynchus mykiss) exhibited kilometer-scale movements among streams during the summer growing season. Although we monitored movements at a small fraction of all tributaries used by grayling and rainbow trout, approximately 50% of individuals moved among two or more streams separated by at least 7 km within a single summer. Movements were concentrated in June and July, and subsided by early August. The decline in movements coincided with spawning by anadromous sockeye salmon, which offer a high-quality resource pulse of food to resident species. Inter-stream movements may represent prospecting behavior as individuals seek out the most profitable foraging opportunities that are patchily distributed across space and time. Our results highlight that large-scale movements may not only be necessary for individuals to fulfill their life-cycle, but also to exploit heterogeneously spaced trophic resources. Therefore, habitat fragmentation and homogenization may have strong, but currently undescribed, ecological effects on the access to critical food resources in stream-dwelling fish populations. PMID- 26379236 TI - Inhibition of Inactive States of Tetrodotoxin-Sensitive Sodium Channels Reduces Spontaneous Firing of C-Fiber Nociceptors and Produces Analgesia in Formalin and Complete Freund's Adjuvant Models of Pain. AB - While genetic evidence shows that the Nav1.7 voltage-gated sodium ion channel is a key regulator of pain, it is unclear exactly how Nav1.7 governs neuronal firing and what biophysical, physiological, and distribution properties of a pharmacological Nav1.7 inhibitor are required to produce analgesia. Here we characterize a series of aminotriazine inhibitors of Nav1.7 in vitro and in rodent models of pain and test the effects of the previously reported "compound 52" aminotriazine inhibitor on the spiking properties of nociceptors in vivo. Multiple aminotriazines, including some with low terminal brain to plasma concentration ratios, showed analgesic efficacy in the formalin model of pain. Effective concentrations were consistent with the in vitro potency as measured on partially-inactivated Nav1.7 but were far below concentrations required to inhibit non-inactivated Nav1.7. Compound 52 also reversed thermal hyperalgesia in the complete Freund's adjuvant (CFA) model of pain. To study neuronal mechanisms, electrophysiological recordings were made in vivo from single nociceptive fibers from the rat tibial nerve one day after CFA injection. Compound 52 reduced the spontaneous firing of C-fiber nociceptors from approximately 0.7 Hz to 0.2 Hz and decreased the number of action potentials evoked by suprathreshold tactile and heat stimuli. It did not, however, appreciably alter the C-fiber thresholds for response to tactile or thermal stimuli. Surprisingly, compound 52 did not affect spontaneous activity or evoked responses of Adelta-fiber nociceptors. Results suggest that inhibition of inactivated states of TTX-S channels, mostly likely Nav1.7, in the peripheral nervous system produces analgesia by regulating the spontaneous discharge of C-fiber nociceptors. PMID- 26379238 TI - Methylatable Signaling Helix Coordinated Inhibitory Receiver Domain in Sensor Kinase Modulates Environmental Stress Response in Bacillus Cereus. AB - sigmaB, an alternative transcription factor, controls the response of the cell to a variety of environmental stresses in Bacillus cereus. Previously, we reported that RsbM negatively regulates sigmaB through the methylation of RsbK, a hybrid sensor kinase, on a signaling helix (S-helix). However, RsbK comprises a C terminal receiver (REC) domain whose function remains unclear. In this study, deletion of the C-terminal REC domain of RsbK resulted in high constitutive sigmaB expression independent of environmental stimuli. Thus, the REC domain may serve as an inhibitory element. Mutagenic substitution was employed to modify the putative phospho-acceptor residue D827 in the REC domain of RsbK. The expression of RsbKD827N and RsbKD827E exhibited high constitutive sigmaB, indicating that D827, if phosphorylatable, possibly participates in sigmaB regulation. Bacterial two-hybrid analyses demonstrated that RsbK forms a homodimer and the REC domain interacts mainly with the histidine kinase (HK) domain and partly with the S helix. In particular, co-expression of RsbM strengthens the interaction between the REC domain and the S-helix. Consistently, our structural model predicts a significant interaction between the HK and REC domains of the RsbK intradimer. Here, we demonstrated that coordinated the methylatable S-helix and the REC domain of RsbK is functionally required to modulate sigmaB-mediated stress response in B. cereus and maybe ubiquitous in microorganisms encoded RsbK-type sensor kinases. PMID- 26379239 TI - Model-Based Reasoning in Humans Becomes Automatic with Training. AB - Model-based and model-free reinforcement learning (RL) have been suggested as algorithmic realizations of goal-directed and habitual action strategies. Model based RL is more flexible than model-free but requires sophisticated calculations using a learnt model of the world. This has led model-based RL to be identified with slow, deliberative processing, and model-free RL with fast, automatic processing. In support of this distinction, it has recently been shown that model based reasoning is impaired by placing subjects under cognitive load--a hallmark of non-automaticity. Here, using the same task, we show that cognitive load does not impair model-based reasoning if subjects receive prior training on the task. This finding is replicated across two studies and a variety of analysis methods. Thus, task familiarity permits use of model-based reasoning in parallel with other cognitive demands. The ability to deploy model-based reasoning in an automatic, parallelizable fashion has widespread theoretical implications, particularly for the learning and execution of complex behaviors. It also suggests a range of important failure modes in psychiatric disorders. PMID- 26379240 TI - Acinetobacter baumannii Virulence Is Mediated by the Concerted Action of Three Phospholipases D. AB - Acinetobacter baumannii causes a broad range of opportunistic infections in humans. Its success as an emerging pathogen is due to a combination of increasing antibiotic resistance, environmental persistence and adaptation to the human host. To date very little is known about the molecular basis of the latter. Here we demonstrate that A. baumannii can use phosphatidylcholine, an integral part of human cell membranes, as sole carbon and energy source. We report on the identification of three phospholipases belonging to the PLD superfamily. PLD1 and PLD2 appear restricted to the bacteria and display the general features of bacterial phospholipases D. They possess two PLDc_2 PFAM domains each encompassing the HxKx4Dx6GS/GGxN (HKD) motif necessary for forming the catalytic core. The third candidate, PLD3, is found in bacteria as well as in eukaryotes and harbours only one PLDc_2 PFAM domain and one conserved HKD motif, which however do not overlap. Employing a markerless mutagenesis system for A. baumannii ATCC 19606T, we generated a full set of PLD knock-out mutants. Galleria mellonella infection studies as well as invasion experiments using A549 human lung epithelial cells revealed that the three PLDs act in a concerted manner as virulence factors and are playing an important role in host cell invasion. PMID- 26379241 TI - Conservation Status of a Recently Described Endemic Land Snail, Candidula coudensis, from the Iberian Peninsula. AB - We assessed the distribution, population size and conservation status of Candidula coudensis, a recently described endemic land snail from Portugal. From March 2013 to April 2014, surveys were carried out in the region where the species was described. We found an extent of occurrence larger than originally described, but still quite small (13.5 km2). The species was found mainly in olive groves, although it occurred in a variety of other habitats with limestone soils, including grasslands, scrublands and stone walls. Minimum population estimate ranged from 110,000-311,000 individuals. The main identified potential threats to the species include wildfires, pesticides and quarrying. Following the application of IUCN criteria, we advise a conservation status of either "Least Concern" or "Near-threatened" under criterion D (restricted population). PMID- 26379243 TI - Environmental Limits of Tall Shrubs in Alaska's Arctic National Parks. AB - We sampled shrub canopy volume (height times area) and environmental factors (soil wetness, soil depth of thaw, soil pH, mean July air temperature, and typical date of spring snow loss) on 471 plots across five National Park Service units in northern Alaska. Our goal was to determine the environments where tall shrubs thrive and use this information to predict the location of future shrub expansion. The study area covers over 80,000 km2 and has mostly tundra vegetation. Large canopy volumes were uncommon, with volumes over 0.5 m3/m2 present on just 8% of plots. Shrub canopy volumes were highest where mean July temperatures were above 10.5 degrees C and on weakly acid to neutral soils (pH of 6 to 7) with deep summer thaw (>80 cm) and good drainage. On many sites, flooding helped maintain favorable soil conditions for shrub growth. Canopy volumes were highest where the typical snow loss date was near 20 May; these represent sites that are neither strongly wind-scoured in the winter nor late to melt from deep snowdrifts. Individual species varied widely in the canopy volumes they attained and their response to the environmental factors. Betula sp. shrubs were the most common and quite tolerant of soil acidity, cold July temperatures, and shallow thaw depths, but they did not form high-volume canopies under these conditions. Alnus viridis formed the largest canopies and was tolerant of soil acidity down to about pH 5, but required more summer warmth (over 12 degrees C) than the other species. The Salix species varied widely from S. pulchra, tolerant of wet and moderately acid soils, to S. alaxensis, requiring well-drained soils with near neutral pH. Nearly half of the land area in ARCN has mean July temperatures of 10.5 to 12.5 degrees C, where 2 degrees C of warming would bring temperatures into the range needed for all of the potential tall shrub species to form large canopies. However, limitations in the other environmental factors would probably prevent the formation of large shrub canopies on at least half of the land area with newly favorable temperatures after 2 degrees C of warming. PMID- 26379242 TI - B Cells and Programmed Death-Ligand 2 Signaling Are Required for Maximal Interferon-gamma Recall Response by Splenic CD4+ Memory T Cells of Mice Vaccinated with Mycobacterium tuberculosis Ag85B. AB - CD4+ T cells producing interferon-gamma are crucial for protection against Mycobacterium tuberculosis infection and are the cornerstone of tuberculosis vaccination and immunological diagnostic assays. Since emerging evidence indicates that B cells can modulate T cell responses to M. tuberculosis infection, we investigated the contribution of B cells in regulating interferon gamma recall response by memory Thelper1 cells specific for Ag85B, a leading candidate for tuberculosis sub-unit vaccines. We found that B cells were able to maximize the reactivation of CD4+ memory T cells and the interferon-gamma response against ex vivo antigen recall in spleens of mice vaccinated with Ag85B. B cell-mediated increase of interferon-gamma response was particular evident for high interferon-gamma producer CD4+ memory T cells, likely because those T cells were required for triggering and amplification of B cell activation. A positive feedback loop of mutual activation between B cells, not necessarily antigen experienced but with integral phosphatidylinositol-3 kinase (PI3K) pathway and a peculiar interferon-gamma-producing CD4highT cell subset was established. Programed death-ligand 2 (PD-L2), expressed both on B and the highly activated CD4high T cells, contributed to the increase of interferon-gamma recall response through a PD1-independent pathway. In B cell-deficient mice, interferon-gamma production and activation of Ag85B-specific CD4+ T cells were blunted against ex vivo antigen recall but these responses could be restored by adding B cells. On the other hand, B cells appeared to down-regulate interleukin-22 recall response. Our data point out that nature of antigen presenting cells determines quality and size of T cell cytokine recall responses. Thus, antigen presenting cells, including B cells, deserve to be considered for a better prediction of cytokine responses by peripheral memory T cells specific for M. tuberculosis antigens. We also invite to consider B cells, PD-L2 and PI3K as potential targets for therapeutic modulation of T cell cytokine responses for tuberculosis control. PMID- 26379244 TI - Chronic Running Exercise Alleviates Early Progression of Nephropathy with Upregulation of Nitric Oxide Synthases and Suppression of Glycation in Zucker Diabetic Rats. AB - Exercise training is known to exert multiple beneficial effects including renal protection in type 2 diabetes mellitus and obesity. However, the mechanisms regulating these actions remain unclear. The present study evaluated the effects of chronic running exercise on the early stage of diabetic nephropathy, focusing on nitric oxide synthase (NOS), oxidative stress and glycation in the kidneys of Zucker diabetic fatty (ZDF) rats. Male ZDF rats (6 weeks old) underwent forced treadmill exercise for 8 weeks (Ex-ZDF). Sedentary ZDF (Sed-ZDF) and Zucker lean (Sed-ZL) rats served as controls. Exercise attenuated hyperglycemia (plasma glucose; 242 +/- 43 mg/dL in Sed-ZDF and 115 +/- 5 mg/dL in Ex-ZDF) with increased insulin secretion (plasma insulin; 2.3 +/- 0.7 and 5.3 +/- 0.9 ng/mL), reduced albumin excretion (urine albumin; 492 +/- 70 and 176 +/- 11 mg/g creatinine) and normalized creatinine clearance (9.7 +/- 1.4 and 4.5 +/- 0.8 mL/min per body weight) in ZDF rats. Endothelial (e) and neuronal (n) NOS expression in kidneys of Sed-ZDF rats were lower compared with Sed-ZL rats (p<0.01), while both eNOS and nNOS expression were upregulated by exercise (p<0.01). Furthermore, exercise decreased NADPH oxidase activity, p47phox expression (p<0.01) and alpha-oxoaldehydes (the precursors for advanced glycation end products) (p<0.01) in the kidneys of ZDF rats. Additionally, morphometric evidence indicated renal damage was reduced in response to exercise. These data suggest that upregulation of NOS expression, suppression of NADPH oxidase and alpha-oxoaldehydes in the kidneys may, at least in part, contribute to the renal protective effects of exercise in the early progression of diabetic nephropathy in ZDF rats. Moreover, this study supports the theory that chronic aerobic exercise could be recommended as an effective non-pharmacological therapy for renoprotection in the early stages of type 2 diabetes mellitus and obesity. PMID- 26379245 TI - Statins Increase Plasminogen Activator Inhibitor Type 1 Gene Transcription through a Pregnane X Receptor Regulated Element. AB - Plasminogen activator inhibitor type 1 (PAI-1) is a multifunctional protein that has important roles in inflammation and wound healing. Its aberrant regulation may contribute to many disease processes such as heart disease. The PAI-1 promoter is responsive to multiple inputs including cytokines, growth factors, steroids and oxidative stress. The statin drugs, atorvastatin, mevastatin and rosuvastatin, increased basal and stimulated expression of the PAI-1 promoter 3 fold. A statin-responsive, nuclear hormone response element was previously identified in the PAI-1 promoter, but it was incompletely characterized. We characterized this direct repeat (DR) of AGGTCA with a 3-nucleotide spacer at 269/-255 using deletion and directed mutagenesis. Deletion or mutation of this element increased basal transcription from the promoter suggesting that it repressed PAI-1 transcription in the unliganded state. The half-site spacing and the ligand specificity suggested that this might be a pregnane X receptor (PXR) responsive element. Computational molecular docking showed that atorvastatin, mevastatin and rosuvastatin were structurally compatible with the PXR ligand binding pocket in its agonist conformation. Experiments with Gal4 DNA binding domain fusion proteins showed that Gal4-PXR was activated by statins while other DR + 3 binding nuclear receptor fusions were not. Overexpression of PXR further enhanced PAI-1 transcription in response to statins. Finally, ChIP experiments using Halo-tagged PXR and RXR demonstrated that both components of the PXR-RXR heterodimer bound to this region of the PAI-1 promoter. PMID- 26379246 TI - Microbial Regulation of p53 Tumor Suppressor. AB - p53 tumor suppressor has been identified as a protein interacting with the large T antigen produced by simian vacuolating virus 40 (SV40). Subsequent research on p53 inhibition by SV40 and other tumor viruses has not only helped to gain a better understanding of viral biology, but also shaped our knowledge of human tumorigenesis. Recent studies have found, however, that inhibition of p53 is not strictly in the realm of viruses. Some bacterial pathogens also actively inhibit p53 protein and induce its degradation, resulting in alteration of cellular stress responses. This phenomenon was initially characterized in gastric epithelial cells infected with Helicobacter pylori, a bacterial pathogen that commonly infects the human stomach and is strongly linked to gastric cancer. Besides H. pylori, a number of other bacterial species were recently discovered to inhibit p53. These findings provide novel insights into host-bacteria interactions and tumorigenesis associated with bacterial infections. PMID- 26379247 TI - A Mitochondrion-Targeted Antioxidant Ameliorates Isoflurane-Induced Cognitive Deficits in Aging Mice. AB - Isoflurane possesses neurotoxicity and can induce cognitive deficits, particularly in aging mammals. Mitochondrial reactive oxygen species (mtROS) have been linked to the early pathogenesis of this disorder. However, the role of mtROS remains to be evaluated due to a lack of targeted method to treat mtROS. Here, we determined in aging mice the effects of the mitochondrion-targeted antioxidant SS-31, on cognitive deficits induced by isoflurane, a general inhalation anesthetic. We further investigated the possible mechanisms underlying the effects of SS-31 on hippocampal neuro-inflammation and apoptosis. The results showed that isoflurane induced hippocampus-dependent memory deficit, which was associated with mitochondrial dysfunction including reduced ATP contents, increased ROS levels, and mitochondrial swelling. Treatment with SS-31 significantly ameliorated isoflurane-induced cognitive deficits through the improvement of mitochondrial integrity and function. Mechanistically, SS-31 treatment suppressed pro-inflammatory responses by decreasing the levels of NF kappaB, NLRP3, caspase 1, IL-1beta, and TNF-alpha; and inhibited the apoptotic pathway by decreasing the Bax/Bcl-2 ratio, reducing the release of cytochrome C, and blocking the cleavage of caspase 3. Our results indicate that isoflurane induced cognitive deficits may be attenuated by mitochondrion-targeted antioxidants, such as SS-31. Therefore, SS-31 may have therapeutic potentials in preventing injuries from oxidative stresses that contribute to anesthetic-induced neurotoxicity. PMID- 26379250 TI - Correction: In vivo Modeling Implicates APOL1 in Nephropathy: Evidence for Dominant Negative Effects and Epistasis under Anemic Stress. PMID- 26379248 TI - Two Distinct Isoforms of Matrix Metalloproteinase-2 Are Associated with Human Delayed Kidney Graft Function. AB - Delayed graft function (DGF) is a frequent complication of renal transplantation, particularly in the setting of transplantation of kidneys derived from deceased donors and expanded-criteria donors. DGF results from tubular epithelial cell injury and has immediate and long term consequences. These include requirement for post-transplantation dialysis, increased incidence of acute rejection, and poorer long-term outcomes. DGF represents one of the clearest clinical examples of renal acute ischemia/reperfusion injury. Experimental studies have demonstrated that ischemia/reperfusion injury induces the synthesis of the full length secreted isoform of matrix metalloproteinase-2 (FL-MMP-2), as well as an intracellular N-terminal truncated MMP-2 isoform (NTT-MMP-2) that initiates an innate immune response. We hypothesized that the two MMP-2 isoforms mediate tubular epithelial cell injury in DGF. Archival renal biopsy sections from 10 protocol biopsy controls and 41 cases with a clinical diagnosis of DGF were analyzed for the extent of tubular injury, expression of the FL-MMP-2 and NTT-MMP 2 isoforms by immunohistochemistry (IHC), in situ hybridization, and qPCR to determine isoform abundance. Differences in transcript abundance were related to tubular injury score. Markers of MMP-2-mediated injury included TUNEL staining and assessment of peritubular capillary density. There was a clear relationship between tubular epithelial cell expression of both FL-MMP-2 and NTT-MMP-2 IHC with the extent of tubular injury. The MMP-2 isoforms were detected in the same tubular segments and were present at sites of tubular injury. qPCR demonstrated highly significant increases in both the FL-MMP-2 and NTT-MMP-2 transcripts. Statistical analysis revealed highly significant associations between FL-MMP-2 and NTT-MMP-2 transcript abundance and the extent of tubular injury, with NTT-MMP 2 having the strongest association. We conclude that two distinct MMP-2 isoforms are associated with tubular injury in DGF and offer novel therapeutic targets for the prevention of this disorder. PMID- 26379249 TI - Predicting the Effects of Woody Encroachment on Mammal Communities, Grazing Biomass and Fire Frequency in African Savannas. AB - With grasslands and savannas covering 20% of the world's land surface, accounting for 30-35% of worldwide Net Primary Productivity and supporting hundreds of millions of people, predicting changes in tree/grass systems is priority. Inappropriate land management and rising atmospheric CO2 levels result in increased woody cover in savannas. Although woody encroachment occurs world-wide, Africa's tourism and livestock grazing industries may be particularly vulnerable. Forecasts of responses of African wildlife and available grazing biomass to increases in woody cover are thus urgently needed. These predictions are hard to make due to non-linear responses and poorly understood feedback mechanisms between woody cover and other ecological responders, problems further amplified by the lack of long-term and large-scale datasets. We propose that a space-for time analysis along an existing woody cover gradient overcomes some of these forecasting problems. Here we show, using an existing woody cover gradient (0 65%) across the Kruger National Park, South Africa, that increased woody cover is associated with (i) changed herbivore assemblage composition, (ii) reduced grass biomass, and (iii) reduced fire frequency. Furthermore, although increased woody cover is associated with reduced livestock production, we found indigenous herbivore biomass (excluding elephants) remains unchanged between 20-65% woody cover. This is due to a significant reorganization in the herbivore assemblage composition, mostly as a result of meso-grazers being substituted by browsers at increasing woody cover. Our results suggest that woody encroachment will have cascading consequences for Africa's grazing systems, fire regimes and iconic wildlife. These effects will pose challenges and require adaptation of livelihoods and industries dependent on conditions currently prevailing. PMID- 26379251 TI - Different characteristics of circular staplers make the difference in anastomotic tensile strength. AB - Anastomotic leak after gastrointestinal surgery is a severe complication associated with relevant short and long-term sequelae. Most of the anastomoses are currently performed with a surgical stapler that is required to have appropriate characteristics in order to guarantee good performances. The aim of our study was to evaluate, ex vivo, pressure resistance and tensile strength of anastomosis performed with different circular staplers available in the market. We studied 7 circular staplers of 3 different companies, 3 of them used for gastrointestinal anastomosis and 4 staplers for hemorrhoidal prolapse excision. A total of 350 anastomoses, 50 for each of the 7 staplers, were performed using healthy pig fresh intestine, then injected saline solution and recorded the leaking pressure. There were no statistically significant differences between the mean pressure necessary to induce an anastomotic leak in the various instruments (p>0.05). For studying tensile strength, we performed a total of 350 anastomoses with 7 different circular staplers on a special strong paper (Tyvek), and then recorded the maximal tensile force that could open the anastomosis. There were statistically significant differences between one brand stapler vs other 2 companies staplers about the strength necessary to open the staple line (p<0.05). In conclusion, we demonstrated that different circular staplers of three companies available in the market give comparable anastomotic pressure resistance but different tensile strengths. This is probably due to different technical characteristics. PMID- 26379252 TI - Appearance comparison in individuals with body dysmorphic disorder and controls. AB - Research investigating appearance comparison in body dysmorphic disorder (BDD) remains very limited, despite the fact that this is one of the most commonly observed behaviors in individuals with the disorder. The present study investigated the self-reported extent and nature of appearance comparison in 35 BDD participants relative to 45 controls using a newly devised and a standardized appearance comparison measure. The results showed that BDD participants reported significantly higher levels of appearance comparison than controls. Individuals with BDD also reported greater levels of comparing in terms of the specific feature(s) of their appearance they were most concerned about as compared to overall appearance, whilst controls showed the opposite pattern. Levels of comparing in BDD participants increased as targets increased in terms of attractiveness, and individuals with BDD rated themselves as being markedly less attractive than targets, and feeling markedly less satisfied with their appearance after comparing. Cognitive-behavioral treatment implications are discussed. PMID- 26379253 TI - Interrater Reliability of the ENERGY Photo-Rating Instrument for School Environments Related to Physical Activity and Eating. AB - BACKGROUND: The school environment can play an important role in the prevention of childhood overweight and obesity. Photos of the school environment may contribute to more adequate measurement of the school environment, as photos can be rated by different assessors. We aimed to examine the interrater reliability for rating characteristics of primary school environments related to physical activity and eating. METHODS: Photos taken at 172 primary schools in 7 European countries were rated according to a standardized protocol. Briefly, after categorizing all photos in subsections of physical activity or eating opportunities, 2 researchers independently rated aspects of safety, functionality, aesthetics, type of food/drinks advertised, type/variety of foods provided. Interrater reliability was assessed using the intraclass correlation coefficient (ICC) and Cohen's kappa. RESULTS: Six subsections of the photo-rating instrument showed excellent (ICC or Cohen's kappa >=0.81) or good (ICC or Cohen's kappa 0.61 to 0.80) interrater reliability. Outdoor physical activity facilities (ICC = 0.54) showed moderate, and school canteens (Cohen's kappa = 0.05) and vending machines showed poor (Cohen's kappa = 0.16) interrater reliability. CONCLUSION: Interrater reliability of the ENERGY (EuropeaN Energy balance Research to prevent excessive weight Gain among Youth) photo-rating instrument was good-to-excellent for 6 out of 9 characteristics of primary school environment components related to physical activity and eating. PMID- 26379254 TI - Assessing the effect of agricultural land abandonment on bird communities in southern-eastern Europe. AB - Agricultural land abandonment is recognized as a major environmental threat in Europe, being particularly pronounced in south-eastern Europe, where knowledge on its effects is limited. Taking the Balkan Peninsula as a case study, we investigated agricultural abandonment impact on passerine communities at regional level. We set up a standard methodology for site selection (70 sites) and data collection, along a well-defined forest-encroachment gradient that reflects land abandonment in four countries: Albania, Bulgaria, Croatia and Greece. Regardless the different socio-economic and political histories in the Balkans that led to diverse land abandonment patterns in space and time, rural abandonment had a consistent negative effect on bird communities, while regional-level analysis revealed patterns that were hidden at local level. The general trends were an increase of forest-dwelling bird species at the expense of farmland birds, the decline of overall bird species richness, as well as the decline of Species of European Conservation Concern (SPECs) richness and abundance. Many farmland bird species declined with land abandonment, whereas few forest species benefited from the process. In conclusion, our results support CAP towards hampering rural land abandonment and preserving semi-open rural mosaics in remote upland areas, using a suite of management measures carefully tailored to local needs. The maintenance of traditional rural landscapes should be prioritized in the Balkans, through the timely identification of HNV farmland that is most prone to abandonment. We also suggest that coordinated transnational research is needed, for a better assessment of conservation options in remote rural landscapes at European scale, including the enhancement of wild grazers' populations as an alternative in areas where traditional land management is rather unlikely to be re-established. PMID- 26379255 TI - A review of corporate sustainability reporting tools (SRTs). AB - Sustainability reporting has been increasingly adopted by corporations worldwide given the demand of stakeholders for greater transparency on both environmental and social issues. The popularity of such reporting is evidenced by the development of a range of tools in the last two decades - Global Reporting Initiative (GRI), AA1000 and Carbon Disclosure Project (CDP) inter alia. These tools, referred to collectively as corporate sustainability reporting tools (SRTs) are important as they serve to inform the progress of corporations towards achieving sustainability goals. However, the rapid growth of corporate SRTs, with different criteria and methodology has created major complications for stakeholders. This paper makes a genuine contribution by providing a review of some of these major tools, spanning across a wide spectrum - framework, standards, ratings and indices. A critique of SRTs is also given. Institutional investors, governments, practitioners and individuals may find this review useful in terms of understanding the nature of different corporate SRTs. As well, it can serve as a useful reference for the development of the next generation of corporate SRTs. PMID- 26379256 TI - Characterizing the conformational dynamics of metal-free PsaA using molecular dynamics simulations and electron paramagnetic resonance spectroscopy. AB - Prokaryotic metal-ion receptor proteins, or solute-binding proteins, facilitate the acquisition of metal ions from the extracellular environment. Pneumococcal surface antigen A (PsaA) is the primary Mn(2+)-recruiting protein of the human pathogen Streptococcus pneumoniae and is essential for its in vivo colonization and virulence. The recently reported high-resolution structures of metal-free and metal-bound PsaA have provided the first insights into the mechanism of PsaA facilitated metal binding. However, the conformational dynamics of metal-free PsaA in solution remain unknown. Here, we use continuous wave electron paramagnetic resonance (EPR) spectroscopy and molecular dynamics (MD) simulations to study the relative flexibility of the structural domains in metal-free PsaA and its distribution of conformations in solution. The results show that the crystal structure of metal-free PsaA is a good representation of the dominant conformation in solution, but the protein also samples structurally distinct conformations that are not captured by the crystal structure. Further, these results suggest that the metal binding site is both larger and more solvent exposed than indicated by the metal-free crystal structure. Collectively, this study provides atomic-resolution insight into the conformational dynamics of PsaA prior to metal binding and lays the groundwork for future EPR and MD based studies of PsaA in solution. PMID- 26379257 TI - Landscape history improves detection of marginal habitats on semi-natural grasslands. AB - Semi-natural grassland habitats have markedly declined from their historical coverage, thus causing substantial losses for agricultural biodiversity and establishing a consequent need to spot the remaining habitat patches. These patches are generally remnants of once larger habitat areas, formed by uninterrupted and low-intensity management for centuries, but then later being isolated and fragmented into smaller pieces. In the light of this development, past landscape phases have a crucial role for the present existence of semi natural grasslands. The importance of historical factors has been indicated in many studies but evaluation of their added value, or actual site-specific effects compared to observations of only the present landscape characteristics, is not generally provided. As data related to the past is often difficult to obtain, tedious to process and challenging to interpret, assessment of its advantages and related effects - or consequences of potential exclusion - would be needed. In this study, we used maximum entropy approach to model the distribution of Fumewort (Corydalis solida) which in the study area is a good indicator of valuable semi-natural habitats. We constructed three different models - one based on only the contemporary environment with expected indicators of habitat stability, one solely on the historical landscape phases and long-term dynamics, and one combining variables from the past and the present. Predictions of the three models were validated and compared with each other, followed by an analysis indicating the similarity of model results with known Fumewort occurrences. Our results indicate that present landscapes may provide workable surrogates to delineate larger core habitats, but utilization of historical data markedly improves the detection of small outlying patches. These conclusions emphasize the importance of previous landscape phases particularly in detecting marginal semi natural grassland habitats, existing in contemporarily suboptimal conditions and being prone to disappear if no further actions are taken. PMID- 26379258 TI - Long term fluctuations of groundwater mine pollution in a sulfide mining district with dry Mediterranean climate: Implications for water resources management and remediation. AB - Water resources management and restoration strategies, and subsequently ecological and human life quality, are highly influenced by the presence of short and long term cycles affecting the intensity of a targeted pollution. On this respect, a typical acid mine drainage (AMD) groundwater from a sulfide mining district with dry Mediterranean climate (Iberian Pyrite Belt, SW Spain) was studied to unravel the effect of long term weather changes in water flow rate and metal pollutants concentration. Three well differentiated polluting stages were observed and the specific geochemical, mineralogical and hydrological processes involved (pyrite and enclosing rocks dissolution, evaporitic salts precipitation redisolution and pluviometric long term fluctuations) were discussed. Evidencing the importance of including longer background monitoring stage in AMD management and restoration strategies, the present study strongly advise a minimum 5-years period of AMD continuous monitoring previous to the design of any AMD remediation system in regions with dry Mediterranean climate. PMID- 26379259 TI - Evaluating the coupling effects of climate aridity and vegetation restoration on soil erosion over the Loess Plateau in China. AB - In this study, the coupling effects of climate aridity and vegetation restoration on runoff and sediment yield over the Loess Plateau were examined and characterized. To take into consideration the complexity of drought, as well as the varied strengths and weaknesses of different drought measures, two drought indices are selected to identify and evaluate drought variability. The Normalized Difference Vegetation Index (NDVI) data were obtained to monitor and express spatiotemporal variations in vegetation cover. The results show that most regions of the Loess Plateau experienced increasingly severe droughts over the past 40years, and these regions comprise the major source of the Yellow River sediment. Climatic drying initially occurred in the 1990s, and became statistically significant in 2000s. The increasingly severe droughts could negatively impact surface and groundwater supplies as well as soil water storage, but may also minimize surface runoff yield, which is one of the major causes of soil erosion on the Loess Plateau. Vegetation cover on the Loess Plateau was significantly improved after the implementation of "Grain for Green" project, which were helpful for controlling severe soil erosion. With the impacts of the construction of check dams, terraces and large reservoirs, runoff and sediment yield over the Loess Plateau initially exhibited downward trends between 1970 and 1990. After 1990, with the effects of the climate warming and drying, a second sharp reduction in runoff and sediment yield occurred. The coupling effects of climate aridity and vegetation restoration have led to a third significant decrease in runoff and sediment yield over the Loess Plateau after 2000. PMID- 26379260 TI - Characteristics of the alkylphenol and bisphenol A distributions in marine organisms and implications for human health: A case study of the East China Sea. AB - The distributions of alkylphenol (AP) and bisphenol A (BPA) in marine organisms, including fish, prawns and molluscs, could reflect the exposure of AP and BPA directly and effectively. This paper provides the first report on the species dependent distribution and the human health risks of four APs (4-t-octylphenol, 4 t-OP; 4-octylphenol, 4-OP;4-nonylphenol, 4-NP; 4-n-nonylphenol, 4-n-NP) and BPA in 95 wild and 88 processed marine biota samples from the East China Sea of the Yangtze River Delta area. 4-NP was the predominant compound with the highest detected concentration of 19,890.50ng/g ww. Significant pollution was observed in Taizhou, Shanghai and Ningbo. The species-dependent distribution was related to food habits, living patterns and trophic transfer. Higher residual concentrations of 4-t-OP, 4-OP, 4-n-NP and BPA were observed in fish species that consumed benthic organisms or demersal fish species, whereas 4-NP showed different results due to trophic dilution. The trophic magnification factors (TMFs) of the linear APs (4-OP and 4-n-NP) (1.22-2.93) were higher than those of the branched ones (4 t-OP and 4-NP) (0.72-0.90), indicating the relative metabolism stability of linear APs. 4-NP has the lowest TMF value of 0.72, and its trophic dilution might be observed because the branched carbon chain exhibits the lowest dispersion force compared to that of the other APs. As for the health risk, 7-year old children may be exposed to the highest health risk of 4-NP with 95th percentile values of the hazard quotient of 0.22 to 0.23; however, the risks of the other chemicals were relatively low. PMID- 26379261 TI - Estimating the cost of improving service quality in water supply: A shadow price approach for England and wales. AB - Service quality to customers is an aspect that cannot be ignored in the performance assessment of water companies. Nowadays water regulators introduce awards or penalties to incentivize companies to improve service quality to customers when setting prices. In this study, the directional distance function is employed to estimate the shadow prices of variables indicating the lack of service quality to customers in the water industry i.e., written complaints, unplanned interruptions and properties below the reference level. To calculate the shadow price of each undesirable output for each water company, it is needed to ascribe a reference price for the desirable output which is the volume of water delivered. An empirical application is carried out for water companies in England and Wales. Hence, the shadow price of each undesirable output is expressed both as a percentage of the price of the desirable output and in pence per cubic meter of water delivered The estimated results indicate that on average, each additional written complaint that needs to be dealt with by the water company includes a service quality cost of 0.399p/m(3). As expected, when looking at the other service quality variables which involve network repair or replacement, these values are considerably higher. On average, the water company must spend an extra 0.622p/m(3) to prevent one unplanned interruption and 0.702p/m(3) to avoid one water pressure below the reference level. The findings of this study are of great importance for regulated companies and regulators as it has been illustrated that improvements in the service quality in terms of customer service could be challenging and therefore ongoing investments will be required to address these issues. PMID- 26379262 TI - How long can culturable bacteria and total DNA persist in environmental waters? The role of sunlight and solid particles. AB - In this work, sunlight inactivation of two indicator bacteria in freshwater, with and without solid particles, was studied and the persistence of culturable cells and total DNA was compared. Environmental water was used to prepare two matrices, with and without solid particles, which were spiked with Escherichia coli and Enterococcus faecalis. These matrices were used to prepare microcosm bags that were placed in two containers: one exposed to sunlight and the other in the dark. During one month, samples were removed from each container and detection was done by membrane filter technique and real-time PCR. Kinetic parameters were calculated to assess sunlight effect. Indicator bacteria without solid particles exposed to sunlight suffered an immediate decay (<4h) compared with the ones which were shielded from them. In addition, the survival of both bacteria with solid particles varied depending on the situation analyzed (T99 from 3 up to 60days), being always culturable E. coli more persistent than E. faecalis. On the other side, E. faecalis DNA persisted much longer than culturable cells (T99>40h in the dark with particles). In this case active cells were more prone to sunlight than total DNA and the protective effect of solid particles was also observed. Results highlight that the effects caused by the parameters which describe the behavior of culturable microorganisms and total DNA in water are different and must be included in simulation models but without forgetting that these parameters will also depend on bacterial properties, sensitizers, composition, type, and uses of the aquatic environment under assessment. PMID- 26379263 TI - Dynamics of toxicity within different compartments of a peri-urban river subject to combined sewer overflow discharges. AB - Combined Sewer Overflows (CSO) in small peri-urban streams and rivers are potentially toxic for their biocenosis. Improving the management of CSO discharges requires better knowledge of their dynamics and toxicity. In view to characterizing this toxicity, we sampled the different compartments (benthic and hyporheic zone) of a peri-urban stream located near the city of Lyon in France. The samples were taken at different distances from a CSO and at three period characteristic of different hydrological conditions. Their toxic effects were assessed by bioassays on the dissolved fraction (D. magna, V. fisheri and B. calyciflorus bioassays) and on the particle fraction (V. fisheri and H. incongruens bioassays). The results highlighted significant toxicity of the particulate fraction for the benthic and hyporheic samples, in particular downstream of the CSO, but with high spatio-temporal variability. This variability can first be attributed to the variability of CSO discharge sampling as a function of season and rainfall, and the dynamics of polluted particles (trapping of transported particles in infiltration zones, mobilization during floods). These parameters play a fundamental role in the distribution of pollutants according to the geomorphology of stream facies. Regarding dissolved pollutants, the chemical exchanges taking place at the "water-sediment" interface trigger the transfer of pollutants from one phase to another, after which the dispersion of these pollutants is governed by hydraulic flows. Finally, critical zones and periods are identified for the peri-urban river toxicity studied: benthic sediments under mean flow downstream; hyporheic sediments after a storm event downstream, close to the CSO. Recommendations are made on the basis of the knowledge obtained to optimize the management of these discharges. PMID- 26379264 TI - Continuity and change in the development of category-based induction: The test case of diversity-based reasoning. AB - The present research examined the extent to which the cognitive mechanisms available to support inductive inference stay constant across development or undergo fundamental change. Four studies tested how children (ages 5-10) incorporate information about sample composition into their category-based generalizations. Children's use of sample composition varied across age and type of category. For familiar natural kinds, children ages 5-8 generalized similarly from diverse and non-diverse samples of evidence, whereas older children generalized more broadly from more diverse sets. In contrast, for novel categories, children of each age made broader generalizations from diverse than non-diverse samples. These studies provide the first clear evidence that young children are able to incorporate sample diversity into their inductive reasoning. These findings suggest developmental continuity in the cognitive mechanisms available for inductive inference, but developmental changes in the role that prior knowledge plays in shaping these processes. PMID- 26379265 TI - Clinical and radiography results of mini-plate fixation compared to suture suspensory fixation in cervical laminoplasty: A five-year follow-up study. AB - OBJECTIVES: Lamina closure is the most common reason for failure of unilateral open-door laminoplasty. Mini-plate fixation was designed to solve such problem. We assessed the clinical outcomes and radiography results of mini-plate fixation by comparing it with suture suspension fixation. PATIENTS AND METHODS: This prospective study enrolled 57 patients with multi-segment cervical spondylotic myelopathy between January 2008 and March 2010. Thirty-four patients underwent laminoplasty with mini-plate fixation (mini-plate group) whereas 23 patients underwent laminoplasty with suture suspension fixation (suture group). The neurological function was measured with the Japanese Orthopedic Association (JOA) score. Cervical range of motion (ROM), C2-7 angle, and the spinal canal expansive parameters (anteroposterior diameter, Pavlov's ratio, cross-sectional area, and open angles) were evaluated. RESULTS: The mean follow-up time was 64 (60-82) months. There were no significant differences in preoperative JOA scores (p=0.191), postoperative JOA scores (p=0.700), preoperative cervical ROM (p=0.315) and preoperative C2-7 angle (p=0.074) between the two groups. Both groups had significant postoperative JOA improvement (p<0.05). The mini-plate group had larger cervical ROM (p=0.041) and C2-7 angle (p=0.040) than the suture group at the final follow-up. Both groups showed significant improvement in the spinal canal expansive parameters immediately after the surgery. In the suture group, the parameters, such as anteroposterior diameter, Pavlov's ratio, cross sectional area, and open angles, decreased along with time, mainly within the first 6 months following the operation. In the mini-plate group, these parameters remained unchanged. The spinal canal expansive parameters between the 2 groups were not significantly different immediately following the operation, but were significantly different at the final follow-up (p<0.05). Three patients in the suture group displayed neurological deterioration due to lamina reclosure. CONCLUSIONS: Laminoplasty by mini-plate fixation preserved more cervical ROM and better cervical alignment, maintained cervical spine canal expansive stability and effectively avoided lamina reclosure for a long-term follow-up. PMID- 26379266 TI - Sensory Differences and Mealtime Behavior in Children With Autism. AB - This study examined sensory differences and mealtime behaviors in children with autism spectrum disorder (ASD; n=34) and compared the results with those of similarly aged peers who were typically developing (TD; n=34). Results from parent-report and child-report questionnaires indicated that children with ASD scored significantly differently from TD peers on the measures of sensory differences and eating behaviors. Data also supported a correlation between sensory differences and eating difficulties in children with ASD. The results of this study will help caregivers and their children with ASD identify problem eating behaviors that may be associated with sensory differences. Sensory strategies and techniques offered by occupational therapy practitioners may contribute to greater success during mealtimes for children with ASD and their families, with increased comfort and less stress. The findings also support a need to further explore the influence of sensory differences on mealtime behaviors. PMID- 26379267 TI - Doing Philosophy Effectively: Student Learning in Classroom Teaching. AB - An important aim of teaching philosophy in Dutch secondary schools is to learn about philosophy (i.e., the great philosophers) by doing philosophy. We examined doing philosophy and focused specifically on the relationship between student learning activities and teacher behavior; in doing so, a qualitative cross-case analysis of eight philosophy lessons was performed. The effectiveness of doing philosophy was operationalized into five learning activities comprising rationalizing, analyzing, testing, producing criticism, and reflecting, and scored by means of qualitative graphical time registration. Using CA we find a quantitative one-dimensional scale for the lessons that contrasts lessons that are more and less effective in terms of learning and teaching. A relationship was found between teaching by teachers and doing philosophy by students. In particular we found students to produce a higher level of doing philosophy with teachers who chose to organize a philosophical discussion with shared guidance by the teacher together with the students. PMID- 26379268 TI - ZnO Hierarchical Nanostructure Photoanode in a CdS Quantum Dot-Sensitized Solar Cell. AB - A hierarchical array of ZnO nanocones covered with ZnO nanospikes was hydrothermally fabricated and employed as the photoanode in a CdS quantum dot sensitized solar cell (QDSSC). This QDSSC outperformed the QDSSC based on a simple ZnO nanocone photoanode in all the four principal photovoltaic parameters. Using the hierarchical photoanode dramatically increased the short circuit current density and also slightly raised the open circuit voltage and the fill factor. As a result, the conversion efficiency of the QDSSC based on the hierarchical photoanode was more than twice that of the QDSSC based on the simple ZnO nanocone photoanode. This improvement is attributable to both the enlarged specific area of the photoanode and the reduction in the recombination of the photoexcited electrons. PMID- 26379269 TI - Control of Francisella tularensis Intracellular Growth by Pulmonary Epithelial Cells. AB - The virulence of F. tularensis is often associated with its ability to grow in macrophages, although recent studies show that Francisella proliferates in multiple host cell types, including pulmonary epithelial cells. Thus far little is known about the requirements for killing of F. tularensis in the non macrophage host cell types that support replication of this organism. Here we sought to address this question through the use of a murine lung epithelial cell line (TC-1 cells). Our data show that combinations of the cytokines IFN-gamma, TNF, and IL-17A activated murine pulmonary epithelial cells to inhibit the intracellular growth of the F. tularensis Live Vaccine Strain (LVS) and the highly virulent F. tularensis Schu S4 strain. Although paired combinations of IFN gamma, TNF, and IL-17A all significantly controlled LVS growth, simultaneous treatment with all three cytokines had the greatest effect on LVS growth inhibition. In contrast, Schu S4 was more resistant to cytokine-induced growth effects, exhibiting significant growth inhibition only in response to all three cytokines. Since one of the main antimicrobial mechanisms of activated macrophages is the release of reactive nitrogen intermediates (RNI) via the activity of iNOS, we investigated the role of RNI and iNOS in Francisella growth control by pulmonary epithelial cells. NOS2 gene expression was significantly up regulated in infected, cytokine-treated pulmonary epithelial cells in a manner that correlated with LVS and Schu S4 growth control. Treatment of LVS-infected cells with an iNOS inhibitor significantly reversed LVS killing in cytokine treated cultures. Further, we found that mouse pulmonary epithelial cells produced iNOS during in vivo respiratory LVS infection. Overall, these data demonstrate that lung epithelial cells produce iNOS both in vitro and in vivo, and can inhibit Francisella intracellular growth via reactive nitrogen intermediates. PMID- 26379270 TI - The Role of Google Scholar in Evidence Reviews and Its Applicability to Grey Literature Searching. AB - Google Scholar (GS), a commonly used web-based academic search engine, catalogues between 2 and 100 million records of both academic and grey literature (articles not formally published by commercial academic publishers). Google Scholar collates results from across the internet and is free to use. As a result it has received considerable attention as a method for searching for literature, particularly in searches for grey literature, as required by systematic reviews. The reliance on GS as a standalone resource has been greatly debated, however, and its efficacy in grey literature searching has not yet been investigated. Using systematic review case studies from environmental science, we investigated the utility of GS in systematic reviews and in searches for grey literature. Our findings show that GS results contain moderate amounts of grey literature, with the majority found on average at page 80. We also found that, when searched for specifically, the majority of literature identified using Web of Science was also found using GS. However, our findings showed moderate/poor overlap in results when similar search strings were used in Web of Science and GS (10-67%), and that GS missed some important literature in five of six case studies. Furthermore, a general GS search failed to find any grey literature from a case study that involved manual searching of organisations' websites. If used in systematic reviews for grey literature, we recommend that searches of article titles focus on the first 200 to 300 results. We conclude that whilst Google Scholar can find much grey literature and specific, known studies, it should not be used alone for systematic review searches. Rather, it forms a powerful addition to other traditional search methods. In addition, we advocate the use of tools to transparently document and catalogue GS search results to maintain high levels of transparency and the ability to be updated, critical to systematic reviews. PMID- 26379271 TI - Correction: Weather Regulates Location, Timing, and Intensity of Dengue Virus Transmission between Humans and Mosquitoes. PMID- 26379272 TI - Reproducibility of Volumetric Computed Tomography of Stable Small Pulmonary Nodules with Implications on Estimated Growth Rate and Optimal Scan Interval. AB - PURPOSE: To use clinically measured reproducibility of volumetric CT (vCT) of lung nodules to estimate error in nodule growth rate in order to determine optimal scan interval for patient follow-up. METHODS: We performed quantitative vCT on 89 stable non-calcified nodules and 49 calcified nodules measuring 3-13 mm diameter in 71 patients who underwent 3-9 repeat vCT studies for clinical evaluation of pulmonary nodules. Calculated volume standard deviation as a function of mean nodule volume was used to compute error in estimated growth rate. This error was then used to determine the optimal patient follow-up scan interval while fixing the false positive rate at 5%. RESULTS: Linear regression of nodule volume standard deviation versus the mean nodule volume for stable non calcified nodules yielded a slope of 0.057 +/- 0.002 (r2 = 0.79, p<0.001). For calcified stable nodules, the regression slope was 0.052 +/- 0.005 (r2 = 0.65, p = 0.03). Using this with the error propagation formula, the optimal patient follow-up scan interval was calculated to be 81 days, independent of initial nodule volume. CONCLUSIONS: Reproducibility of vCT is excellent, and the standard error is proportional to the mean calculated nodule volume for the range of nodules examined. This relationship constrains statistical certainty of vCT calculated doubling times and results in an optimal scan interval that is independent of the initial nodule volume. PMID- 26379273 TI - Osteogenic Surface Modification Based on Functionalized Poly-P-Xylylene Coating. AB - The biotechnology to immobilize biomolecules on material surfaces has been developed vigorously due to its high potentials in medical applications. In this study, a simple and effective method was designed to immobilize biomolecules via amine-N-hydroxysuccinimide (NHS) ester conjugation reaction using functionalized poly-p-xylylene coating on material surfaces. The NHS ester functionalized coating is synthesized via chemical vapor deposition, a facile and solvent-less method, creating a surface which is ready to perform a one-step conjugation reaction. Bone morphogenetic protein 2 (BMP-2) is immobilized onto material surfaces by this coating method, forming an osteogenic environment. The immobilization process is controlled at a low temperature which does not damage proteins. This modified surface induces differentiation of preosteoblast into osteoblast, manifested by alkaline phosphatase (ALP) activity assay, Alizarin Red S (ARS) staining and the expression of osteogenic gene markers, Alpl and Bglap3. With this coating technology, immobilization of growth factors onto material surface can be achieved more simply and more effectively. PMID- 26379274 TI - Exendin-4 Prevents Vascular Smooth Muscle Cell Proliferation and Migration by Angiotensin II via the Inhibition of ERK1/2 and JNK Signaling Pathways. AB - Angiotensin II (Ang II) is a main pathophysiological culprit peptide for hypertension and atherosclerosis by causing vascular smooth muscle cell (VSMC) proliferation and migration. Exendin-4, a glucagon-like peptide-1 (GLP-1) receptor agonist, is currently used for the treatment of type-2 diabetes, and is believed to have beneficial effects for cardiovascular diseases. However, the vascular protective mechanisms of GLP-1 receptor agonists remain largely unexplained. In the present study, we examined the effect of exendin-4 on Ang II induced proliferation and migration of cultured rat aortic smooth muscle cells (RASMC). The major findings of the present study are as follows: (1) Ang II caused a phenotypic switch of RASMC from contractile type to synthetic proliferative type cells; (2) Ang II caused concentration-dependent RASMC proliferation, which was significantly inhibited by the pretreatment with exendin 4; (3) Ang II caused concentration-dependent RASMC migration, which was effectively inhibited by the pretreatment with exendin-4; (4) exendin-4 inhibited Ang II-induced phosphorylation of ERK1/2 and JNK in a pre-incubation time dependent manner; and (5) U0126 (an ERK1/2 kinase inhibitor) and SP600125 (a JNK inhibitor) also inhibited both RASMC proliferation and migration induced by Ang II stimulation. These results suggest that exendin-4 prevented Ang II-induced VSMC proliferation and migration through the inhibition of ERK1/2 and JNK phosphorylation caused by Ang II stimulation. This indicates that GLP-1 receptor agonists should be considered for use in the treatment of cardiovascular diseases in addition to their current use in the treatment of diabetes mellitus. PMID- 26379275 TI - Efficient Optimization of Stimuli for Model-Based Design of Experiments to Resolve Dynamical Uncertainty. AB - This model-based design of experiments (MBDOE) method determines the input magnitudes of an experimental stimuli to apply and the associated measurements that should be taken to optimally constrain the uncertain dynamics of a biological system under study. The ideal global solution for this experiment design problem is generally computationally intractable because of parametric uncertainties in the mathematical model of the biological system. Others have addressed this issue by limiting the solution to a local estimate of the model parameters. Here we present an approach that is independent of the local parameter constraint. This approach is made computationally efficient and tractable by the use of: (1) sparse grid interpolation that approximates the biological system dynamics, (2) representative parameters that uniformly represent the data-consistent dynamical space, and (3) probability weights of the represented experimentally distinguishable dynamics. Our approach identifies data consistent representative parameters using sparse grid interpolants, constructs the optimal input sequence from a greedy search, and defines the associated optimal measurements using a scenario tree. We explore the optimality of this MBDOE algorithm using a 3-dimensional Hes1 model and a 19-dimensional T-cell receptor model. The 19-dimensional T-cell model also demonstrates the MBDOE algorithm's scalability to higher dimensions. In both cases, the dynamical uncertainty region that bounds the trajectories of the target system states were reduced by as much as 86% and 99% respectively after completing the designed experiments in silico. Our results suggest that for resolving dynamical uncertainty, the ability to design an input sequence paired with its associated measurements is particularly important when limited by the number of measurements. PMID- 26379277 TI - Nucleotides Flanking the Start Codon in hsp70 mRNAs with Very Short 5'-UTRs Greatly Affect Gene Expression in Haloarchaea. AB - Leaderless translation is prevalent in haloarchaea, with many of these leaderless transcripts possessing short 5'-untranslated regions (UTRs) less than 10 nucleotides. Whereas, little is known about the function of this very short 5' UTR. Our previous studies determined that just four nucleotides preceded the start codon of hsp70 mRNA in Natrinema sp. J7, with residues -3A and +4G, relative to the A of the ATG start codon, acting as the preferred bases around the start codon of all known haloarchaeal hsp70 genes. Here, we examined the effects of nucleotides flanking the start codon on gene expression. The results revealed that shortening and deletion of the short 5'-UTR enhanced transcript levels; however, it led to significant reductions in overall translational efficiency. AUG was efficiently used as start codons, in both the presence and absence of short 5'-UTRs. GUG also could initiate translation, even though it was so inefficient that it would not be detected without considerably elevated transcript. Nucleotide substitutions at position -4 to +6 were shown to affect gene expression by transcript and/or translational levels. Notably, -3A and A/U nucleotides at position +4~+6 were more optimal for gene expression. Nucleotide transversions of -3A to -3C and +4G to +4T with hsp70 promoter from either Haloferax volcanii DS70 or Halobacterium salinarum NRC-1 showed the same effects on gene expression as that of Natrinema sp. J7. Taken together, our results suggest that the nucleotides flanking the start codon in hsp70 mRNAs with very short 5'-UTRs play an important role in haloarchaeal gene expression. PMID- 26379276 TI - Novel miRNA-31 and miRNA-200a-Mediated Regulation of Retinoblastoma Proliferation. AB - Retinoblastoma is the most common intraocular tumor in children. Current management includes broad-based treatments such as chemotherapy, enucleation, laser therapy, or cryotherapy. However, therapies that target specific pathways important for retinoblastoma progression could provide valuable alternatives for treatment. MicroRNAs are short, noncoding RNA transcripts that can regulate the expression of target genes, and their aberrant expression often facilitates disease. The identification of post-transcriptional events that occur after the initiating genetic lesions could further define the rapidly aggressive growth displayed by retinoblastoma tumors. In this study, we used two phenotypically different retinoblastoma cell lines to elucidate the roles of miRNA-31 and miRNA 200a in tumor proliferation. Our approach confirmed that miRNAs-31 and -200a expression is significantly reduced in human retinoblastomas. Moreover, overexpression of these two miRNAs restricts the expansion of a highly proliferative cell line (Y79), but does not restrict the growth rate of a less aggressive cell line (Weri1). Gene expression profiling of miRNA-31 and/or miRNA 200a-overexpressing cells identified differentially expressed mRNAs associated with the divergent response of the two cell lines. This work has the potential to enhance the development of targeted therapeutic approaches for retinoblastoma and improve the efficacy of treatment. PMID- 26379278 TI - Are Microalbuminuria and Elevated 24 H Urinary Microalbumin Excretion within Normal Range Associated with Metabolic Syndrome in Chinese Adults? AB - The association of microalbuminuria and elevated 24 h urinary microalbumin excretion (UAE) with metabolic syndrome (MetS) has not been well examined in Chinese Adults. In the present study, a population-based cross-sectional study was conducted among Chinese adults aged 18-69 years in Shandong province in 2011 to determine the relationship between them. Data on 24 h UAE and other variables were obtained and components of MetS were examined. The prevalence of MetS and mean 24 h UAE was 24.7% and 6.7 mg, respectively. Compared with participants with normoalbuminuria, the odds of MetS and its components including central obesity, elevated blood pressure and elevated fasting glucose, but not the odds of low HDL cholesterol and elevated triglycerides, significantly increased in those with microalbuminuria. Additionally, the odds of MetS and its three components significantly increased across increasing quartiles of 24 h UAE within normal range (1.00, 1.11, 1.02 and 1.58, respectively, for MetS; 1.00, 1.14, 1.21, and 1.68, respectively, for central obesity; 1.00, 1.35, 1.26 and 1.68, respectively, for elevated blood pressure; and 1.00, 1.32, 1.06 and 1.47, respectively, for elevated triglycerides; p for linear trend <=0.05 for all). Furthermore, for each increment of 10 mg 24 h UAE within normal range, the odds of MetS and its components including central obesity, elevated blood pressure, and elevated triglycerides significantly increased by 53%, 65%, 55%, and 41%, respectively. These findings suggest that both microalbuminuria and elevated 24 h UAE within normal range might be important risk factors for MetS in Chinese adults. PMID- 26379279 TI - Selective Production of 9R-Hydroxy-10E,12Z,15Z-Octadecatrienoic Acid from alpha Linolenic Acid in Perilla Seed Oil Hydrolyzate by a Lipoxygenase from Nostoc Sp. SAG 25.82. AB - Hydroxy fatty acids (HFAs) derived from omega-3 polyunsaturated fatty acids have been known as versatile bioactive molecules. However, its practical production from omega-3 or omega-3 rich oil has not been well established. In the present study, the stereo-selective enzymatic production of 9R-hydroxy-10E,12Z,15Z octadecatrienoic acid (9R-HOTE) from alpha-linolenic acid (ALA) in perilla seed oil (PO) hydrolyzate was achieved using purified recombinant 9R-lipoxygenase (9R LOX) from Nostoc sp. SAG 25.82. The specific activity of the enzyme followed the order linoleic acid (LA) > ALA > gamma-linolenic acid (GLA). A total of 75% fatty acids (ALA and LA) were used as a substrate for 9R-LOX from commercial PO by hydrolysis of Candida rugosa lipase. The optimal reaction conditions for the production of 9R-HOTE from ALA using 9R-LOX were pH 8.5, 15 degrees C, 5% (v/v) acetone, 0.2% (w/v) Tween 80, 40 g/L ALA, and 1 g/L enzyme. Under these conditions, 9R-LOX produced 37.6 g/L 9R-HOTE from 40 g/L ALA for 1 h, with a conversion yield of 94% and a productivity of 37.6 g/L/h; and the enzyme produced 34 g/L 9R-HOTE from 40 g/L ALA in PO hydrolyzate for 1 h, with a conversion yields of 85% and a productivity of 34 g/L/h. The enzyme also converted 9R hydroxy-10E,12Z-octadecadienoic acid (9R-HODE) from 40 g/L LA for 1.0 h, with a conversion yield of 95% and a productivity of 38.4 g/L. This is the highest productivity of HFA from both ALA and ALA-rich vegetable oil using LOX ever reported. Therefore, our result suggests an efficient method for the production of 9R-HFAs from LA and ALA in vegetable oil using recombinant LOX in biotechnology. PMID- 26379280 TI - Evaluation of Off-Hour Emergency Care in Acute Ischemic Stroke: Results from the China National Stroke Registry. AB - BACKGROUND AND PURPOSE: The quality of after-hour emergency care of patients with acute ischemic stroke is debatable. We therefore, sought to analyze the performance measures, quality of care and clinical outcomes in these patients admitted during off-hours. METHODS: Our study included 4493 patients from a selected cohort of patients admitted to the hospitals with ischemic stroke in the China National Stroke Registry (CNSR) from September 2007 to August 2008. On-hour presentation was defined as arrival at the emergency department from the scene between 8AM and 5PM from Monday through Friday. Off-hours included the remainder of the on-hours and statutory holidays. The association between off-hour presentation and outcome was analyzed using multivariate logistic-regression models. RESULTS: Off-hour presentation was identified in 2672 (59.5%) patients with ischemic stroke. Comparison of patients admitted during off-hours with those admitted during on-hours revealed an unadjusted odds ratio of in-hospital mortality of 1.38 (95% confidence interval, 1.04-1.85), which declined to 1.34 (95% confidence interval, 0.93-1.93) after adjusting for patient characteristics (especially, pre-hospital delay). No difference in 30-day mortality, total death or dependence at three, six and 12 months between two groups was observed. No association between off-hour admission and quality of care was found. CONCLUSIONS: In the CNSR database, compared with on-hour patients, off-hour patients with acute ischemic stroke admitted to the emergency departments from scene manifested a higher incidence of in-hospital mortality. However, the difference in incidence and quality of care between the groups disappeared after adjusting for pre-hospital delay and other variables. PMID- 26379281 TI - Association between Highly Active Antiretroviral Therapy and Type of Infectious Respiratory Disease and All-Cause In-Hospital Mortality in Patients with HIV/AIDS: A Case Series. AB - BACKGROUND: Respiratory manifestations of HIV disease differ globally due to differences in current availability of effective highly active antiretroviral therapy (HAART) programs and epidemiology of infectious diseases. OBJECTIVE: To describe the association between HAART and discharge diagnosis and all-cause in hospital mortality among hospitalized patients with infectious respiratory disease and HIV/AIDS. MATERIAL AND METHODS: We retrospectively reviewed the records of patients hospitalized at a specialty hospital for respiratory diseases in Mexico City between January 1st, 2010 and December 31st, 2011. We included patients whose discharge diagnosis included HIV or AIDS and at least one infectious respiratory diagnosis. The information source was the clinical chart. We analyzed the association between HAART for 180 days or more and type of respiratory disease using polytomous logistic regression and all-cause hospital mortality by multiple logistic regressions. RESULTS: We studied 308 patients, of whom 206 (66.9%) had been diagnosed with HIV infection before admission to the hospital. The CD4+ lymphocyte median count was 68 cells/mm3 [interquartile range (IQR): 30-150]. Seventy-five (24.4%) cases had received HAART for more than 180 days. Pneumocystis jirovecii pneumonia (PJP) (n = 142), tuberculosis (n = 63), and bacterial community-acquired pneumonia (n = 60) were the most frequent discharge diagnoses. Receiving HAART for more than 180 days was associated with a lower probability of PJP [Adjusted odd ratio (aOR): 0.245, 95% Confidence Interval (CI): 0.08-0.8, p = 0.02], adjusted for sociodemographic and clinical covariates. HAART was independently associated with reduced odds (aOR 0.214, 95% CI 0.06-0.75) of all-cause in-hospital mortality, adjusting for HIV diagnosis previous to hospitalization, age, access to social security, low socioeconomic level, CD4 cell count, viral load, and discharge diagnoses. CONCLUSIONS: HAART for 180 days or more was associated with 79% decrease in all-cause in-hospital mortality and lower frequency of PJP as discharge diagnosis. The prevalence of poorly controlled HIV was high, regardless of whether HIV was diagnosed before or during admission. HIV diagnosis and treatment resources should be improved, and strengthening of HAART program needs to be promoted. PMID- 26379283 TI - Correction: Chronic Conditions and Sleep Problems among Adults Aged 50 years or over in Nine Countries: A Multi-Country Study. PMID- 26379282 TI - The Depsipeptide Romidepsin Reverses HIV-1 Latency In Vivo. AB - Pharmacologically-induced activation of replication competent proviruses from latency in the presence of antiretroviral treatment (ART) has been proposed as a step towards curing HIV-1 infection. However, until now, approaches to reverse HIV-1 latency in humans have yielded mixed results. Here, we report a proof-of concept phase Ib/IIa trial where 6 aviremic HIV-1 infected adults received intravenous 5 mg/m2 romidepsin (Celgene) once weekly for 3 weeks while maintaining ART. Lymphocyte histone H3 acetylation, a cellular measure of the pharmacodynamic response to romidepsin, increased rapidly (maximum fold range: 3.7-7.7 relative to baseline) within the first hours following each romidepsin administration. Concurrently, HIV-1 transcription quantified as copies of cell associated un-spliced HIV-1 RNA increased significantly from baseline during treatment (range of fold-increase: 2.4-5.0; p = 0.03). Plasma HIV-1 RNA increased from <20 copies/mL at baseline to readily quantifiable levels at multiple post infusion time-points in 5 of 6 patients (range 46-103 copies/mL following the second infusion, p = 0.04). Importantly, romidepsin did not decrease the number of HIV-specific T cells or inhibit T cell cytokine production. Adverse events (all grade 1-2) were consistent with the known side effects of romidepsin. In conclusion, romidepsin safely induced HIV-1 transcription resulting in plasma HIV 1 RNA that was readily detected with standard commercial assays demonstrating that significant reversal of HIV-1 latency in vivo is possible without blunting T cell-mediated immune responses. These finding have major implications for future trials aiming to eradicate the HIV-1 reservoir. TRIAL REGISTRATION: clinicaltrials.gov NTC02092116. PMID- 26379284 TI - Multiple Days of Heat Exposure on Firefighters' Work Performance and Physiology. AB - This study assessed the accumulated effect of ambient heat on the performance of, and physiological and perceptual responses to, intermittent, simulated wildfire fighting tasks over three consecutive days. Firefighters (n = 36) were matched and allocated to either the CON (19 degrees C) or HOT (33 degrees C) condition. They performed three days of intermittent, self-paced simulated firefighting work, interspersed with physiological testing. Task repetitions were counted (and converted to distance or area) to determine work performance. Participants were asked to rate their perceived exertion and thermal sensation after each task. Heart rate, core temperature (Tc), and skin temperature (Tsk) were recorded continuously throughout the simulation. Fluids were consumed ad libitum. Urine volume was measured throughout, and urine specific gravity (USG) analysed, to estimate hydration. All food and fluid consumption was recorded. There was no difference in work output between experimental conditions. However, significant variation in performance responses between individuals was observed. All measures of thermal stress were elevated in the HOT, with core and skin temperature reaching, on average, 0.24 +/- 0.08 degrees C and 2.81 +/- 0.20 degrees C higher than the CON group. Participants' doubled their fluid intake in the HOT condition, and this was reflected in the USG scores, where the HOT participants reported significantly lower values. Heart rate was comparable between conditions at nearly all time points, however the peak heart rate reached each circuit was 7 +/- 3% higher in the CON trial. Likewise, RPE was slightly elevated in the CON trial for the majority of tasks. Participants' work output was comparable between the CON and HOT conditions, however the performance change over time varied significantly between individuals. It is likely that the increased fluid replacement in the heat, in concert with frequent rest breaks and task rotation, assisted with the regulation of physiological responses (e.g., heart rate, core temperature). PMID- 26379285 TI - RAMBO-K: Rapid and Sensitive Removal of Background Sequences from Next Generation Sequencing Data. AB - BACKGROUND: The assembly of viral or endosymbiont genomes from Next Generation Sequencing (NGS) data is often hampered by the predominant abundance of reads originating from the host organism. These reads increase the memory and CPU time usage of the assembler and can lead to misassemblies. RESULTS: We developed RAMBO K (Read Assignment Method Based On K-mers), a tool which allows rapid and sensitive removal of unwanted host sequences from NGS datasets. Reaching a speed of 10 Megabases/s on 4 CPU cores and a standard hard drive, RAMBO-K is faster than any tool we tested, while showing a consistently high sensitivity and specificity across different datasets. CONCLUSIONS: RAMBO-K rapidly and reliably separates reads from different species without data preprocessing. It is suitable as a straightforward standard solution for workflows dealing with mixed datasets. Binaries and source code (java and python) are available from http://sourceforge.net/projects/rambok/. PMID- 26379287 TI - When Do Fathers Care? Mothers' Economic Contribution and Fathers' Involvement in Child Care. AB - Previous literature suggests a tenuous link between fathers' care of children and maternal employment and earnings. This study shows that the link is stronger when measures of caregiving capture fathers' increased responsibility for children. The analysis of time diary data from 6,572 married fathers and 7,376 married mothers with children under age 13 indicates that fathers (1) engage in more "solo" care of children when their wives are employed, (2) are more likely to do the kind of child care associated with responsibility for their children when their wives spend more time in the labor market, and (3) participate more in routine care when their wives contribute a greater share of the couple's earnings. In addition, the "father care" to "mother care" ratio rises when mothers contribute a greater share of household earnings. PMID- 26379286 TI - Recurrent Domestication by Lepidoptera of Genes from Their Parasites Mediated by Bracoviruses. AB - Bracoviruses are symbiotic viruses associated with tens of thousands of species of parasitic wasps that develop within the body of lepidopteran hosts and that collectively parasitize caterpillars of virtually every lepidopteran species. Viral particles are produced in the wasp ovaries and injected into host larvae with the wasp eggs. Once in the host body, the viral DNA circles enclosed in the particles integrate into lepidopteran host cell DNA. Here we show that bracovirus DNA sequences have been inserted repeatedly into lepidopteran genomes, indicating this viral DNA can also enter germline cells. The original mode of Horizontal Gene Transfer (HGT) unveiled here is based on the integrative properties of an endogenous virus that has evolved as a gene transfer agent within parasitic wasp genomes for ~100 million years. Among the bracovirus genes thus transferred, a phylogenetic analysis indicated that those encoding C-type-lectins most likely originated from the wasp gene set, showing that a bracovirus-mediated gene flux exists between the 2 insect orders Hymenoptera and Lepidoptera. Furthermore, the acquisition of bracovirus sequences that can be expressed by Lepidoptera has resulted in the domestication of several genes that could result in adaptive advantages for the host. Indeed, functional analyses suggest that two of the acquired genes could have a protective role against a common pathogen in the field, baculovirus. From these results, we hypothesize that bracovirus-mediated HGT has played an important role in the evolutionary arms race between Lepidoptera and their pathogens. PMID- 26379288 TI - 'Scholarly peer reviewing': The art, its joys and woes. AB - Research and publications are an important part of academics. Nowadays, there is an increasing trend amongst professionals including anaesthesiologists to submit scientific articles to journals for publication. Most journals are peer-reviewed which means that the articles they publish go through the peer review process. Peer review is carried out for assessing the inadequacies of research and manuscript preparation so that the best papers are published in a journal. Although peer review is a key part of the process for the publishing of medical research, there are some limitations in the system. Keeping this in mind, all aspects of peer reviewing were searched from books and journals for full text from PubMed and Google search. The information so gathered is presented in this article which focuses on the general aspects of the peer review process. PMID- 26379289 TI - Comparison of different doses of magnesium sulphate and fentanyl as adjuvants to bupivacaine for infraumbilical surgeries under subarachnoid block. AB - BACKGROUND AND AIMS: Spinal anaesthesia is used for many years for surgeries below the level of umbilicus. It has certain disadvantages such as limited duration of blockade and post-operative analgesia. This study was undertaken to evaluate the effects of additives fentanyl and magnesium sulphate along with bupivacaine during spinal anaesthesia for prolongation of analgesia and motor blockade. METHODS: This randomised study was conducted in 120 patients of either sex of American Society of Anesthesiologists physical status I and II, posted for infraumbilical surgeries. Patients were randomly allocated to four groups and were given the following drugs intrathecally as per group distribution; group A - bupivacaine 15 mg (0.5% heavy) with fentanyl 25 MUg, group B - bupivacaine 15 mg (0.5% heavy) with magnesium 100 mg, group C - bupivacaine 15 mg (0.5% heavy) with magnesium 50 mg and group D - bupivacaine 15 mg (0.5% heavy) with 0.5 ml normal saline. Parameters monitored were duration of analgesia along with haemodynamic parameters and side effects. Data were analysed using the Student's t-test for the continuous variables and two-tailed Fisher exact test or Chi-square test for categorical variables. RESULTS: There was significant increase in duration of analgesia in group A (374.37 min) and B (328.13 min) as compared to group C (274.87 min) and D (246.03 min). In group A, all haemodynamic parameters decreased by more than 20%, compared to baseline parameters, which was clinically and statistically significant as compared to other groups. There was also increase in duration of motor blockade in groups A and B. CONCLUSION: Addition of magnesium sulphate at 100 mg dose or fentanyl 25 MUg as adjuvants to intrathecal bupivacaine significantly prolongs the duration of analgesia, though in the given doses, magnesium provides better haemodynamic stability than fentanyl, with fewer side effects. PMID- 26379290 TI - A prospective comparative study to evaluate the utility of lung ultrasonography to improve the accuracy of traditional clinical methods to confirm position of left sided double lumen tube in elective thoracic surgeries. AB - BACKGROUND AND AIMS: Traditional clinical methods like auscultation or inspection have been found to be inaccurate in confirmation of double-lumen tube (DLT) position. Lung ultrasonography (USG) reliably identifies the tidal movement (lung sliding) and the collapse of the lung (lung pulse). We intended to check whether the accuracy of clinical methods can be improved by the addition of USG in confirmation of left DLT (LDLT) position. METHODS: A single centred, prospective, comparative study was conducted involving 70 patients undergoing thoracic surgeries requiring the use of LDLT. The patients were assigned to Group A - where LDLT position was assessed by using clinical methods alone, and Group B - where LDLT position was assessed by USG and clinical methods. The correct position was predicted when USG demonstrated the absence of lung sliding and the presence of lung pulse on the operative side, the presence of lung sliding on non operative side, along with normal airway pressures and oxygenation. The final verification of LDLT position was done by direct observation of lung isolation by one surgeon who was blinded to the method of confirmation. Contingency tables were drawn to calculate sensitivity, specificity, positive predictive value, negative predictive value and accuracy of each method. RESULTS: Compared to clinical methods alone, addition of lung USG improved sensitivity (75% vs. 88%), specificity (18% vs. 75%) and accuracy (57% vs. 85%) for correct prediction of LDLT position. CONCLUSION: USG is a useful addition to the armamentarium of anaesthesiologist for the confirmation of LDLT position. PMID- 26379291 TI - Comparison between sevoflurane and desflurane on emergence and recovery characteristics of children undergoing surgery for spinal dysraphism. AB - BACKGROUND AND AIMS: Rapid recovery is desirable after neurosurgery as it enables early post-operative neurological evaluation and prompt management of complications. Studies have been rare comparing the recovery characteristics in paediatric neurosurgical patients. Hence, this study was carried out to compare the effect of sevoflurane and desflurane anaesthesia on emergence and extubation in children undergoing spinal surgery. METHODS: Sixty children, aged 1-12 years, undergoing elective surgery for lumbo-sacral spinal dysraphism were enrolled. Anaesthesia was induced with sevoflurane using a face mask. The children were then randomised to receive either sevoflurane or desflurane with oxygen and nitrous oxide, fentanyl (1 MUg/kg/h) and rocuronium. The anaesthetic depth was guided by bispectral index (BIS((r))) monitoring with a target BIS((r)) between 45 and 55. Perioperative data with regard to demographic profile, haemodynamics, emergence and extubation times, modified Aldrete score (MAS), pain (objective pain score), agitation (Cole's agitation score), time to first analgesic and complications, thereof, were recorded. Statistical analysis was done using STATA 11.2 (StataCorp., College Station, TX, USA) and data are presented as median (range) or mean +/- standard deviation. RESULTS: The demographic profile, haemodynamics, MAS, pain and agitation scores and time to first analgesic were comparable in between the two groups (P > 0.05). The emergence time was shorter in desflurane group (2.75 [0.85-12] min) as compared to sevoflurane (8 [2.5-14] min) (P < 0.0001). The extubation time was also shorter in desflurane group (3 [0.8-10] min) as compared to the sevoflurane group (5.5 [1.2-14] min) (P = 0.0003). CONCLUSION: Desflurane provided earlier tracheal extubation and emergence as compared to sevoflurane in children undergoing surgery for lumbo sacral spinal dysraphism. PMID- 26379292 TI - Dexmedetomidine versus ketamine infusion to alleviate propofol injection pain: A prospective randomized and double-blind study. AB - BACKGROUND AND AIMS: The use of propofol as the most common induction agent and the high prevalence of propofol injection pain (PIP) highlight the significance of finding the ideal combination of drug, dosage and mode of administration of premedicants to alleviate PIP. A number of bolus drugs with variable efficacy have been studied to reduce PIP. The aim of our study was to assess the efficacy of single dose intravenous (IV) infusion of dexmedetomidine 0.5 MUg/kg compared with ketamine 0.5 mg/kg to alleviate PIP. METHODS: In this prospective, randomised and double-blind study, 108 patients undergoing elective surgeries under general anaesthesia were randomly allocated to two groups: Group D to receive dexmedetomidine 0.5MUg/kg or Group K to receive ketamine 0.5 mg/kg in 20 ml of normal saline over 10 min. Immediately after the infusion, 1% propofol 2 mg/kg IV was injected over 25 s. The patients were assessed for pain every 5 s by asking the question 'does it hurt?' until the loss of consciousness. The pain scoring was done using McCririck and Hunter scale. Statistical analysis was done using SPSS 17.0. RESULTS: The incidence of PIP and moderate-severe PIP was higher with Group D (79.6%; 16.7%) compared with Group K (40.7; 1.9%) (P < 0.001; 0.016). No patient in either group had arm withdrawal upon propofol injection. The incidence of hypertension and tachycardia was statistically significant in Group K as compared to Group D (P = 0.027). CONCLUSION: There was no difference in elimination of the arm withdrawal response and in incidence of moderate to severe PIP between the groups. PMID- 26379293 TI - Comparative study of ultrasound-guided paravertebral block with ropivacaine versus bupivacaine for post-operative pain relief in children undergoing thoracotomy for patent ductus arteriosus ligation surgery. AB - BACKGROUND AND AIMS: Thoracotomy incision following patent ductus arteriosus (PDA) ligation surgery is often associated with severe post-operative pain that has deleterious effects on respiratory function. We aimed to assess pain relief with thoracic paravertebral block using either bupivacaine or ropivacaine in these surgeries. METHODS: One hundred paediatric patients of age group between 2 and 10 years undergoing PDA ligation surgery were randomised either to bupivacaine or ropivacaine group in this prospective double-blinded study. After induction of general anaesthesia, the ultrasound-guided paravertebral block was carried out using 0.25% bupivacaine 0.4 ml/kg in Group B patients and 0.2% ropivacaine 0.4 ml/kg in Group R patients. Monitoring included minimum mandatory monitoring with pulse rate, pulseoximetry (SpO2), electrocardiogram, blood pressure, temperature during surgery and also in Intensive Care Unit (ICU). Additionally, modified objective pain score (MOPS) was used in ICU for assessment of pain for 12 h after surgery. Incidence of complications was noted. RESULTS: Mean values of MOPSs were comparable in both the groups. The time to rescue analgesic was 8 to 10 h in over 80% of patients in both the groups. More patients had hypotension and bradycardia in bupivacaine group compared to ropivacaine group. CONCLUSION: Paravertebral injection of 0.4 ml/kg of either 0.2% ropivacaine or 0.25% bupivacaine provided equipotent analgesia, but ropivacaine had a better side effect profile. Ultrasound-guided paravertebral block is a safe and effective mode of analgesia in paediatric patients undergoing thoracotomy. PMID- 26379294 TI - Ruptured intrathoracic cyst during induction of anaesthesia: Anaesthetic challenges. AB - Congenital benign cysts are among the rare types of mediastinal masses. When symptomatic, complete surgical excision through thoracotomy is the definitive treatment. Rarely they may present with symptoms due to complications like rupture. However, rupture following the induction of general anaesthesia poses unique challenges for anaesthesiologist. We report our experience of a rare variant of intraparenchymal cyst (lung), which was subsequently found to be a bronchogenic cyst. PMID- 26379295 TI - Thrombocytosis following splenectomy and aortic valve replacement for idiopathic thrombocytopaenic purpura with bicuspid aortic valve. AB - Idiopathic thrombocytopaenic purpura (ITP) patients are at high risk for complications during and after cardiac surgeries involving cardiopulmonary bypass. The main clinical problem of primary ITP is an increased risk of bleeding although bleeding may not always be present. More recently, thrombosis has become appreciated as another potential complication of the procedure. We report a 22 year-old female patient with ITP with bicuspid aortic valve and splenomegaly, who underwent uncomplicated aortic valve replacement and splenectomy simultaneously. She was readmitted with chest pain due to coronary thrombosis following splenectomy which made the management difficult. We describe our experience in managing this patient who presented with thrombotic complication rather than bleeding in post-operative period and the challenges met in maintaining appropriate anticoagulation for aortic valve replacement as well as thrombosis, post-splenectomy. PMID- 26379296 TI - Evaluation of levetiracetam as a pre-operative anxiolytic: A randomized, double blind, placebo-controlled study. PMID- 26379297 TI - Flaccid paralysis following subarachnoid block: A diagnostic dilemma. PMID- 26379298 TI - Anaesthesia information booklet: Is it better than a pre-operative visit? PMID- 26379299 TI - Anaesthesiologist's role in the multidisciplinary approach to placenta percreta. PMID- 26379300 TI - Anaesthetic concerns in an infant with a rare genetic condition; chromosome 9p22 deletion syndrome. PMID- 26379301 TI - A case of Behcet's disease posted for surgery: Anaesthetic implications. PMID- 26379302 TI - Spinal epidural haematoma following rivaroxaban administration after total knee replacement. PMID- 26379303 TI - Noninvasive cardiac output monitoring during anaesthetic management for caesarean delivery in parturient with severe mitral stenosis: A more relaxed look. PMID- 26379304 TI - Sternal cleft: Anaesthetic management of a rare congenital anomaly. PMID- 26379305 TI - The anaesthetic management of patient with amiodarone-induced thyrotoxicosis posted for thyroidectomy. PMID- 26379306 TI - A novel technique for safe paediatric blood transfusion. PMID- 26379307 TI - Is flat line truly asystole? PMID- 26379308 TI - Comparative evaluation of femoral nerve block and intravenous fentanyl for positioning during spinal anaesthesia for surgery of femur fracture. PMID- 26379309 TI - Glycine induced retinotoxicity is avoidable. PMID- 26379310 TI - A Simulation Study on the Performance of the Simple Difference and Covariance Adjusted Scores in Randomized Experimental Designs. AB - Research by Huck and McLean (1975) demonstrated that the covariance-adjusted score is more powerful than the simple difference score, yet recent reviews indicate researchers are equally likely to use either score type in two-wave randomized experimental designs. A Monte Carlo simulation was conducted to examine the conditions under which the simple difference and covariance-adjusted scores were more or less powerful to detect treatment effects when relaxing certain assumptions made by Huck and McLean (1975). Four factors were manipulated in the design including sample size, normality of the pretest and posttest distributions, the correlation between pretest and posttest, and posttest variance. A 5 * 5 * 4 * 3 mostly crossed design was run with 1,000 replications per condition, resulting in 226,000 unique samples. The gain score was nearly as powerful as the covariance-adjusted score when pretest and posttest variances were equal, and as powerful in fan-spread growth conditions; thus, under certain circumstances the gain score could be used in two-wave randomized experimental designs. PMID- 26379311 TI - Does Biology Justify Ideology? The Politics of Genetic Attribution. AB - Conventional wisdom suggests that political conservatives are more likely than liberals to endorse genetic explanations for many human characteristics and behaviors. Whether and to what extent this is true has received surprisingly limited systematic attention. We examine evidence from a large U.S. public opinion survey that measured the extent to which respondents believed genetic explanations account for a variety of differences among individuals as well as groups in society. We find that conservatives were indeed more likely than liberals to endorse genetic explanations for perceived race and class differences in characteristics often associated with socioeconomic inequality (intelligence, math skills, drive, and violence). Different ideological divisions emerged, however, with respect to respondents' explanations for sexual orientation. Here, liberals were more likely than conservatives to say that sexual orientation is due to genes and less likely to say that it is due to choice or the environment. These patterns suggest that conservative and liberal ideologues will tend to endorse genetic explanations where their policy positions are bolstered by "naturalizing" human differences. That said, debates over genetic influence may be more politicized with respect to race, class, and sexual orientation than population differences generally: We find that left/right political ideology was not significantly associated with genetic (or other) attributions for individual differences in intelligence, math skills, drive, or violence. We conclude that conceptions of the proper role of government are closely intertwined with assumptions about the causes of human difference, but that this relationship is a complex one. PMID- 26379312 TI - Vitamin D3 May Ameliorate the Ketoconazole Induced Adrenal Injury: Histological and Immunohistochemical Studies on Albino Rats. AB - Ketoconazole (KZ) is used widely for treating the superficial, systemic fungal activities and hyperandrogenemic states. Its uses are limited by its deleterious effect on histological structure and function of the adrenal cortex. This study investigates whether vitamin D3 supplement can ameliorate the morphological changes induced by KZ. Thirty four adult male albino rats were randomized into control group (Group I) which was subdivided into: control 1 (n=7) and control 2 (n=7): In control 1, rats were intraperitoneal (I.P) injected once with 1 ml of polyethylene glycol-400 for 15 consecutive days and control 2 rats were injected I.P with (1 MUg/kg) of vitamin D3 for the same period. Group II (n=10): rats were I.P injected with KZ (10 mg/100 g of body weight) once daily for 15 days; Group III (n=10): rats were I.P concomitantly injected with KZ and vitamin D3 similar doses to animals in groups II and control 2 respectively. Blood samples were collected to determine plasma ACTH, corticosterone and aldosterone levels. The right adrenal specimens sections were stained with Haematoxylin & Eosin and Masson Trichrome for histological studies and treated with Bax, Ubiquitin and vitamin D receptors for immunohistochemical studies. KZ induced adrenal cortical morphological changes in forms of disturbed adrenocorticocyte cytological architecture, nuclear changes, and intracellular lipid accumulation. KZ also increased adrenal Bax and Ub but decreased the vitamin D receptors immunopositive staining expression, in addition to increased plasma ACTH as well as decreased corticosterone and aldosterone levels. These changes were ameliorated by supplementing with vitamin D3. PMID- 26379313 TI - Reactivation of CDX2 in Gastric Cancer as Mark for Gene Silencing Memory. AB - To explore the epigenetic mechanism that reactivates CDX2 (a homeobox transcription factor that serves as a tumor-suppressor gene) in intestinal-type gastric cancer during cancer progression, we examined the methylation status of the CDX2 gene promoter and the expression pattern of methyl-CpG binding protein-2 (MeCP2). From archives of the pathology records of surgically excised advanced stomach cancer cases in the Department of Molecular Pathology, Ehime University in a past decate (n=265), 10 cases of intestinal-type tubular adenocarcinoma, well-differentiated type (wel) with minor poorly-differentiated adenocarcinoma (por) components were selected. The expression pattern of CDX2, MUC2 and MeCP2 in these 10 cases was analyzed by immunohistochemistry. The cancerous and non cancerous areas were selectively obtained by microdissection, and the methylation status of the CDX2 promoter of each area was assessed by methylation-specific polymerase chain reaction (MSP). In all 10 cases, CDX2 expression was clearly observed in the nucleus of the non-cancerous background of the intestinal metaplasic area, where the unmethylation pattern of the CDX2 gene promoter prevailed with reduced MeCP2 expression. In this metaplastic area, CDX2 expression was co-localized with its target gene, MUC2. CDX2 expression then disappeared from the deep invasive wel area. Reflecting the reduced CDX2 expression, microdissected samples from all the wel areas showed hypermethylation of the CDX2 gene promoter by MSP, with prominent MeCP2 expression. Interestingly, while hypermethylation of the CDX2 gene promoter was maintained in the por area in 8 of the 10 cases, CDX2 expression was restored in por areas where MeCP2 expression was markedly and selectively reduced. The other two cases, however, showed a constant MeCP2 expression level comparable to the surrounding deep invasive wel area with negative CDX2 expression. Therefore, gene silencing by hypermethylation may be overcome by the reduction of methyl-CpG binding proteins, resulting in apparent but non-functional reactivation of CDX2 as a mere molecular mark for gene silencing memory. PMID- 26379314 TI - Localization of Nitric Oxide Synthase-containing Neurons in the Bat Visual Cortex and Co-localization with Calcium-binding Proteins. AB - Microchiroptera (microbats) is a suborder of bats thought to have degenerated vision. However, many recent studies have shown that they have visual ability. In this study, we labeled neuronal nitric oxide synthase (nNOS)-the synthesizing enzyme of the gaseous non-synaptic neurotransmitter nitric oxide-and co-localized it with calbindin D28K (CB), calretinin (CR), and parvalbumin (PV) in the visual cortex of the greater horseshoe bat (Rhinolophus ferrumequinum, a species of microbats). nNOS-immunoreactive (IR) neurons were found in all layers of the visual cortex. Intensely labeled neurons were most common in layer IV, and weakly labeled neurons were most common in layer VI. Majority of the nNOS-IR neurons were round- or oval-type neurons; no pyramidal-type neurons were found. None of these neurons co-localized with CB, CR, or PV. However, the synthesis of nitric oxide in the bat visual cortex by nNOS does not depend on CB, CR, or PV. PMID- 26379315 TI - What's wrong? Moral understanding in psychopathic offenders. PMID- 26379316 TI - Sensitivity to imputation models and assumptions in receiver operating characteristic analysis with incomplete data. AB - Modern statistical methods using incomplete data have been increasingly applied in a wide variety of substantive problems. Similarly, receiver operating characteristic (ROC) analysis, a method used in evaluating diagnostic tests or biomarkers in medical research, has also been increasingly popular problem in both its development and application. While missing-data methods have been applied in ROC analysis, the impact of model mis-specification and/or assumptions (e.g. missing at random) underlying the missing data has not been thoroughly studied. In this work, we study the performance of multiple imputation (MI) inference in ROC analysis. Particularly, we investigate parametric and non parametric techniques for MI inference under common missingness mechanisms. Depending on the coherency of the imputation model with the underlying data generation mechanism, our results show that MI generally leads to well-calibrated inferences under ignorable missingness mechanisms. PMID- 26379317 TI - Can chest high-resolution computed tomography findings diagnose pulmonary alveolar microlithiasis? AB - OBJECTIVE: The present study was aimed at retrospectively reviewing high resolution computed tomography (HRCT) findings in patients with pulmonary alveolar microlithiasis in order to evaluate the frequency of tomographic findings and their distribution in the lung parenchyma. MATERIALS AND METHODS: Thirteen patients (9 females and 4 males; age, 9 to 59 years; mean age, 34.5 years) were included in the present study. The HRCT images were independently evaluated by two observers whose decisions were made by consensus. The inclusion criterion was the presence of abnormalities typical of pulmonary alveolar microlithiasis at HRCT, which precludes lung biopsy. However, in 6 cases lung biopsy was performed. RESULTS: Ground-glass opacities and small parenchymal nodules were the predominant tomographic findings, present in 100% of cases, followed by small subpleural nodules (92.3%), subpleural cysts (84.6%), subpleural linear calcifications (69.2%), crazy-paving pattern (69.2%), fissure nodularity (53.8%), calcification along interlobular septa (46.2%) and dense consolidation (46.2%). CONCLUSION: As regards distribution of the lesions, there was preferential involvement of the lower third of the lungs. No predominance of distribution in axial and anteroposterior directions was observed. PMID- 26379318 TI - Computed tomography-guided percutaneous trephine removal of the nidus in osteoid osteoma patients: experience of a single center in Brazil. AB - OBJECTIVE: To report the results of computed tomography (CT)-guided percutaneous resection of the nidus in 18 cases of osteoid osteoma. MATERIALS AND METHODS: The medical records of 18 cases of osteoid osteoma in children, adolescents and young adults, who underwent CT-guided removal of the nidus between November, 2004 and March, 2009 were reviewed retrospectively for demographic data, lesion site, clinical outcome and complications after procedure. RESULTS: Clinical follow-up was available for all cases at a median of 29 months (range 6-60 months). No persistence of pre-procedural pain was noted on 17 patients. Only one patient experienced recurrence of symptoms 12 months after percutaneous resection, and was successfully retreated by the same technique, resulting in a secondary success rate of 18/18 (100%). CONCLUSION: CT-guided removal or destruction of the nidus is a safe and effective alternative to surgical resection of the osteoid osteoma nidus. PMID- 26379319 TI - Magnetic resonance imaging and BMB score in the evaluation of bone involvement in Gaucher's disease patients. AB - OBJECTIVE: To evaluate by magnetic resonance imaging changes in bone marrow of patients undergoing treatment for type I Gaucher's disease. MATERIALS AND METHODS: Descriptive, cross-sectional study of Gaucher's disease patients submitted to 3 T magnetic resonance imaging of femurs and lumbar spine. The images were blindly reviewed and the findings were classified according to the semiquantitative bone marrow burden (BMB) scoring system. RESULTS: All of the seven evaluated patients (three men and four women) presented signs of bone marrow infiltration. Osteonecrosis of the femoral head was found in three patients, Erlenmeyer flask deformity in five, and no patient had vertebral body collapse. The mean BMB score was 11, ranging from 9 to 14. CONCLUSION: Magnetic resonance imaging is currently the method of choice for assessing bone involvement in Gaucher's disease in adults due to its high sensitivity to detect both focal and diffuse bone marrow changes, and the BMB score is a simplified method for semiquantitative analysis, without depending on advanced sequences or sophisticated hardware, allowing for the classification of the disease extent and assisting in the treatment monitoring. PMID- 26379320 TI - Sonographic evaluation of children with congenital hypothyroidism. AB - OBJECTIVE: To establish benchmarks and study some sonographic characteristics of the thyroid gland in a group of euthyroid children aged up to 5 years as compared with age-matched children with congenital hypothyroidism. MATERIALS AND METHODS: Thirty-six children (17 female and 19 male) aged between 2 months and 5 years were divided into two groups - 23 euthyroid children and 13 children with congenital hypothyroidism - and were called to undergo ultrasonography. RESULTS: In the group of euthyroid children (n = 23), mean total volume of the thyroid gland was 1.12 mL (minimum, 0.39 mL; maximum, 2.72 mL); a homogeneous gland was found in 17 children (73.91%) and 6 children (26.08%) had a heterogeneous gland. In the group of children with congenital hypothyroidism (n = 13), mean total volume of the thyroid gland was 2.73 mL (minimum, 0.20 mL; maximum, 11.00 mL). As regards thyroid location, 3 patients (23.07%) had ectopic thyroid, and 10 (69.23%) had topic thyroid, and out of the latter, 5 had a homogeneous gland (50%) and 5, a heterogeneous gland (50%). In the group with congenital hypothyroidism, 6 (46.15%) children had etiological diagnosis of dyshormoniogenesis, 3 (23.07%), of ectopic thyroid, and 4 (30.76%), of thyroid hypoplasia. CONCLUSION: Thyroid ultrasonography is a noninvasive imaging method, widely available, easy to perform and for these reasons could, and should, be performed at any time, including at birth, with no preparation or treatment discontinuation, to aid in the early etiological definition of congenital hypothyroidism. PMID- 26379322 TI - Coronary anomalies: what the radiologist should know. AB - Coronary anomalies comprise a diverse group of malformations, some of them asymptomatic with a benign course, and the others related to symptoms as chest pain and sudden death. Such anomalies may be classified as follows: 1) anomalies of origination and course; 2) anomalies of intrinsic coronary arterial anatomy; 3) anomalies of coronary termination. The origin and the proximal course of anomalous coronary arteries are the main prognostic factors, and interarterial course or a coronary artery is considered to be malignant due its association with increased risk of sudden death. Coronary computed tomography angiography has become the reference method for such an assessment as it detects not only anomalies in origination of these arteries, but also its course in relation to other mediastinal structures, which plays a relevant role in the definition of the therapeutic management. Finally, it is essential for radiologists to recognize and characterize such anomalies. PMID- 26379321 TI - Accuracy of computer-aided ultrasound as compared with magnetic resonance imaging in the evaluation of nonalcoholic fatty liver disease in obese and eutrophic adolescents. AB - OBJECTIVE: To compare the accuracy of computer-aided ultrasound (US) and magnetic resonance imaging (MRI) by means of hepatorenal gradient analysis in the evaluation of nonalcoholic fatty liver disease (NAFLD) in adolescents. MATERIALS AND METHODS: This prospective, cross-sectional study evaluated 50 adolescents (aged 11-17 years), including 24 obese and 26 eutrophic individuals. All adolescents underwent computer-aided US, MRI, laboratory tests, and anthropometric evaluation. Sensitivity, specificity, positive and negative predictive values and accuracy were evaluated for both imaging methods, with subsequent generation of the receiver operating characteristic (ROC) curve and calculation of the area under the ROC curve to determine the most appropriate cutoff point for the hepatorenal gradient in order to predict the degree of steatosis, utilizing MRI results as the gold-standard. RESULTS: The obese group included 29.2% girls and 70.8% boys, and the eutrophic group, 69.2% girls and 30.8% boys. The prevalence of NAFLD corresponded to 19.2% for the eutrophic group and 83% for the obese group. The ROC curve generated for the hepatorenal gradient with a cutoff point of 13 presented 100% sensitivity and 100% specificity. As the same cutoff point was considered for the eutrophic group, false-positive results were observed in 9.5% of cases (90.5% specificity) and false-negative results in 0% (100% sensitivity). CONCLUSION: Computer-aided US with hepatorenal gradient calculation is a simple and noninvasive technique for semiquantitative evaluation of hepatic echogenicity and could be useful in the follow-up of adolescents with NAFLD, population screening for this disease as well as for clinical studies. PMID- 26379323 TI - Artifacts and pitfalls in shoulder magnetic resonance imaging. AB - Magnetic resonance imaging has revolutionized the diagnosis of shoulder lesions, in many cases becoming the method of choice. However, anatomical variations, artifacts and the particularity of the method may be a source of pitfalls, especially for less experienced radiologists. In order to avoid false-positive and false-negative results, the authors carried out a compilation of imaging findings that may simulate injury. It is the authors' intention to provide a useful, consistent and comprehensive reference for both beginner residents and skilled radiologists who work with musculoskeletal magnetic resonance imaging, allowing for them to develop more precise reports and helping them to avoid making mistakes. PMID- 26379324 TI - Magnetic resonance imaging of the vagina: an overview for radiologists with emphasis on clinical decision making. AB - Magnetic resonance imaging is a method with high contrast resolution widely used in the assessment of pelvic gynecological diseases. However, the potential of such method to diagnose vaginal lesions is still underestimated, probably due to the scarce literature approaching the theme, the poor familiarity of radiologists with vaginal diseases, some of them relatively rare, and to the many peculiarities involved in the assessment of the vagina. Thus, the authors illustrate the role of magnetic resonance imaging in the evaluation of vaginal diseases and the main relevant findings to be considered in the clinical decision making process. PMID- 26379325 TI - Ortner's syndrome: a case report and literature review. AB - The authors report the case of a 55-year-old female, hypertensive, smoker patient presenting with dysphonia, dysphagia and persistent dry cough. Laryngoscopy diagnosed left vocal cord paralysis. Computed tomography demonstrated saccular aneurysm of the inferior wall of the aortic arch, stretching the left recurrent laryngeal nerve, a finding compatible with Ortner's syndrome. PMID- 26379326 TI - Teratoma: a set of teeth in the pelvis. PMID- 26379327 TI - Dactylolysis spontanea (ainhum). PMID- 26379328 TI - Uncommon presentation of perforated Meckel's diverticulum in preterm newborn. PMID- 26379329 TI - Desmoplastic fibroma with perineural spread: conventional and diffusion-weighted magnetic resonance imaging findings. PMID- 26379330 TI - Creutzfeldt-Jakob dementia. PMID- 26379331 TI - Glomus tumor: revitalizing concepts. PMID- 26379332 TI - Incidentalomas: managing risks. PMID- 26379333 TI - Osteoid osteoma: diagnosis and treatment. PMID- 26379334 TI - (18)F-fluoride PET/CT in clinical practice. PMID- 26379335 TI - Brain stem cell division and maintenance studied using multi-isotope imaging mass spectrometry (MIMS). AB - New neurons are continuously produced from neural stem cells in specific regions of the adult brain of animals and humans. In the hippocampus, a region crucial for cognitive function, neurogenesis responds to a multitude of extrinsic stimuli; emerging evidence indicates that it may be important for behavior, pathophysiology, brain repair, and response to drugs. We have developed an approach to identify and quantify the cellular targets of pro- and anti neurogenic stimuli, based on reporter transgenic mouse lines in which neural stem and progenitor cells or their progeny are marked by fluorescent proteins. Here, we demonstrate the feasibility of using MIMS for studying adult neurogenesis. PMID- 26379336 TI - Effect of an anti-depressant on mouse hippocampus protein turnover using MIMS. AB - Although antidepressants have been used in the treatment of affective disorders for over fifty years, the precise mechanism of their action remains unknown. Treatment regimens are based by and large on empirical parameters and characterized by a trial and error scheme. A better understanding of the mechanisms involved in antidepressant drug response is of fundamental importance for the development of new compounds that have a higher success rate and specificity. In order to elucidate the molecular pathways involved in the action of antidepressants, we wish to identify brain areas, cell types, and organelles that are targeted by antidepressant treatment in mice. Multi-isotope Imaging Mass Spectrometry (MIMS) allows a quantitative approach to this analysis, allowing us to delineate antidepressant effect on protein synthesis in the brain at single cell and organelle resolution. In these experiments, we obtained a global analysis of protein turnover in the hippocampus dentate gyrus (DG) and in the Cornu Ammonis (CA) regions, together with a subcellular analysis in the granular cells and others. PMID- 26379337 TI - Detection of immunolabels with multi-isotope imaging mass spectrometry (MIMS). AB - We have developed a method that combines the use of stable isotopes, MIMS and antibody. We began with using well-established antibodies, anti-actin and anti synaptophysin, in mouse intestinal cells. We extended the method to an immunogold assay to specifically localize Ribeye, a major protein component of retina synaptic ribbons, or to localize a synaptic vesicle-containing protein, synaptophysin. Both are localized in presynaptic nerve terminal of photoreceptors cells in retina. Our results show that by MIMS analysis of the Au signal we can directly identify antibodies tagged with non amplified 1.4 nm gold nanoparticles. They also demonstrate that the gold nanoparticle-tagged antibodies do not dilute the 15N/14N signal used for measuring protein turnover. Thus we can simultaneously and directly use MIMS to measure protein turnover and to identify cell type or specific protein. PMID- 26379338 TI - Quantitative imaging of selenoprotein with multi-isotope imaging mass spectrometry (MIMS). AB - Multi-isotope imaging mass spectrometry (MIMS) allows high resolution quantitative imaging of protein and nucleic acid synthesis at the level of a single cell using stable isotope labels. We employed MIMS to determine the compartmental localization of selenoproteins tagged with stable isotope selenium compounds in human aortic endothelial cells (HAEC), and to compare the efficiency of labeling (to determine the ideal selenium source) from these compounds: [82Se] selenite, [77Se]-seleno-methionine, and [76Se]-methyl-selenocysteine. We found that all three selenium sources appear to be localized in the nucleus as well as in the cytoplasm in HAEC. Seleno-methionine appears to be a better source for (seleno)protein synthesis. For MIMS detection, we compared freeze-drying to thin layer vs. thin sectioning for sample preparation. MIMS provides a unique and novel way to dissect selenoprotein synthesis in cells. PMID- 26379339 TI - Study of protein and RNA in dendritic spines using multi-isotope imaging mass spectrometry (MIMS). AB - The classical view of neuronal protein synthesis is that proteins are made in the cell body and then transported to their functional sites in the dendrites and the dendritic spines. Indirect evidence, however, suggests that protein synthesis can directly occur in the distal dendrites, far from the cell body. We are developing protocols for dual labeling of RNA and proteins using 15N-uridine and 18O- or 13C leucine pulse chase in cultured neurons to identify and localize both protein synthesis and fate of newly synthesized proteins. Pilot experiments show discrete localization of both RNA and newly synthesized proteins in dendrites, close to dendritic spines. We have for the first time directly imaged and measured the production of proteins at the subcellular level in the neuronal dendrites, close to the functional sites, the dendritic spines. This will open a powerful way to study neural growth and synapse plasticity in health and disease. PMID- 26379340 TI - Quantifying cell division with deuterated water and multi-isotope imaging mass spectrometry (MIMS). AB - Cell division is commonly quantified by the administration of nucleotide labels that are incorporated by the nucleotide salvage pathway. A new approach uses precursors of the de novo nucleotide synthesis pathway, such as labeled water or glucose. Because such precursors are not specific for DNA synthesis, studies utilizing this approach have analyzed isolated genomic DNA to exclude nonspecific background labeling. We hypothesized that pulse-chase administration of stable isotope labeled water would result in sufficient nuclear labeling to enable discrimination of recently divided cells by quantitative ion microscopy. We administered deuterated (D)-water and 15N-thymidine to mice concurrently, guided by the rationale that 15N-thymidine incorporation would serve as a "gold standard" to identify dividing cells. We show both qualitatively and quantitatively that dividing cells in the small intestine (15N-labeled) demonstrate a discernable D-signal in the nucleus not observed in undivided cells (15N-unlabled). Correlation with 31P- and 12C15N-:12C14N- images demonstrate preferential localization of 2H labeling in regions of the nucleus with high DNA content as expected of labeling being incorporated during DNA synthesis and cell division. These data support the concept that stable isotope tagged precursors of the de novo nucleotide synthesis pathway can be used in concert with NanoSIMS to study cell division in vivo. A major implication of this study then is the possibility of using stable isotope tagged water and MIMS to study human cell turnover. PMID- 26379341 TI - Approaches to increasing analytical throughput of human samples with multi isotope imaging mass spectrometry. AB - Multi-isotope imaging mass spectrometry (MIMS) combines stable isotope tracers with the quantitative imaging of NanoSIMS ion microscopy. With extensive safety precedent, use of stable isotopes in MIMS applications opens the possibility of studying a wide array of biological questions in humans[1]. Here we describe a series of approaches to increase the effective analytical throughput for detecting rare nuclear labeling events with MIMS. At the level of sample preparation, cells in suspension were either smeared at high density or pelleted cells were embedded and sectioned to reach nuclear depth. Presputtering conditions were optimized for each cell type to ensure the reproducible sampling of nuclei. Adipose tissue posed a different challenge as the large volume of adipocytes results in an obligatorily low density of nuclei in any given plane. Before introducing samples to the NanoSIMS instrument, all nuclei were fluorescently stained, imaged, and their coordinates recorded, allowing automated analysis of fields that contained at least one nucleus and therefore minimizing analysis of dead space. These data emphasize unique challenges posed by human studies, where both ethical and practical issues may limit the administration of stable isotope labels for prolonged periods of time as may be necessary to achieve high labeling frequencies in cells that divide infrequently. PMID- 26379342 TI - Quantitative imaging of inositol distribution in yeast using multi-isotope imaging mass spectrometry (MIMS). AB - Despite the widely recognized importance of the several species of inositol polyphosphates in cell biology, inositol has not been successfully imaged and quantified inside cells using traditional spectrophotometry. Multi-isotope imaging mass spectrometry (MIMS) technology, however, has facilitated direct imaging and measurement of cellular inositol. After pulsing cells with inositol labeled with the stable isotope Carbon-13 (13C), the label was detected in subcellular volumes by MIMS. The tridimensional localization of 13C within the cell illustrated cellular distribution and local accumulation of inositol. In parallel, we performed control experiments with 13C-Glucose to compare a different 13C distribution pattern. Because many functions recently attributed to inositol polyphosphates are localized in the nucleus, we analyzed its relative nuclear concentration. We engineered yeast with human thymidine permease and viral thymidine kinase, then fed them with 15N-thymidine. This permitted direct analysis of the nuclear DNA through the detection of the 15N isotopic signal. We found practically no co-localization between inositol signal (13C-isotope) and nuclear signal (15N-isotope). The 13C-tag (inositol) accumulation was highest at the plasma membrane and in cytoplasmic domains. In time-course labeling experiments performed with wild type yeast (WT) or modified yeast unable to synthesize inositol from glucose (ino1Delta), the half-time of labeled inositol accumulation was ~1 hour in WT and longer in ino1Delta. These studies should serve as a template to study metabolism and physiological role of inositol using genetically modified yeasts. PMID- 26379343 TI - Anticipated Job Benefits, Career Aspiration, and Generalized Self-efficacy as Predictors for Migration Decision-Making. AB - This study aims to identify person-level factors, rather than economic situations, that influence migration decision-making and actual migration. Building on the theory of planned behavior, this study investigated potential migrants' expectations and attitudes toward migration and career (i.e., anticipated job benefits of migration, career aspiration) as well as beliefs (i.e., generalized self-efficacy) as predictors of migration decision-making conceptualized in three phases: the pre-decisional, pre-actional, and actional phases. This was examined with cross-sectional pre-migration questionnaire data from 1163 potential migrants from Spain to Germany. We also examined whether the migration decision-making phases predicted actual migration with a subsample (n=249) which provided follow-up data within twelve months. For the cross sectional sample, multinomial logistic regressions revealed that anticipated job benefits and career aspiration are predictive for all migration phases. Self efficacy predicts the preactional (e.g., gathering information) and actional phases (e.g., making practical arrangements). Finally, for those with low self efficacy, anticipated job benefits play a stronger role for taking action. For the longitudinal subsample, a logistic regression revealed that being in the preactional and actional phases at baseline is predictive of actual migration within twelve months. This study expands previous research on migration intentions and behaviors by focusing on expectations, values, and beliefs as person-level predictors for migration decision-making. With a longitudinal sample, it shows that international migration is a process that involves multiple phases. PMID- 26379344 TI - Prevalence and Incidence of Multiple Sclerosis in Fars Province, Southern Iran. AB - BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of the central nervous system, which is accompanied by significant disabilities. Although there are some published data regarding the epidemiological features of MS in other parts of Iran, scarce data are available about the prevalence and demographic characteristics of MS in Fars province. The current study aimed to address the prevalence and incidence rate of MS as well as the temporal trend of the disease in Fars province, southern Iran. METHODS: This historical retrospective cohort study was carried out in Fars Multiple Sclerosis Society affiliated with Shiraz University of Medical Sciences. All the consecutive patients who fulfilled 2010 McDonald criteria for definite MS were included in the study. The patients' gender, age at time of diagnosis, education, and clinical course were recorded. The prevalence and incidence rates were also calculated. RESULTS: This study was conducted on 3,354 patients. Among the patients, 2,689 (80.2%) were female and 665 (19.8%) were male. The female/male ratio was 4.04. The point prevalence rate of the disease was 72.1/100,000 persons in October 2013. This index was 116.5 per 100,000 persons in females (95% CI: 113.4-119.6) and 28.3 per 100,000 persons in males (95% CI: 26.8-29.9). The mean annual incidence rate was 5.2/100,000 from 2002 until 2012. CONCLUSION: Considering Kurtzke classification, Fars is a high-risk area for MS and women are affected more compared with men. Moreover, the incidence rate sharply increased in the last decade. PMID- 26379345 TI - The Effect of Cognitive Behavior Therapy in Insomnia due to Methadone Maintenance Therapy: A Randomized Clinical Trial. AB - BACKGROUND: Sleep disturbance is a common complaint of patients undergoing methadone maintenance therapy (MMT). There are limited studies about the effect of different treatments on insomnia due to MMT. In this study, we evaluated the effect of cognitive-behavioral treatment for insomnia (CBTI) on sleep disorders in patients undergoing MMT. METHODS: Twenty-two patients with insomnia due to MMT (aged 18-60 years) participated in this randomized double-blind clinical trial. The intervention group received CBTI from a clinical psychologist for 8 weeks, whereas the control group received behavioral placebo therapy (BPT). The duration of individual sessions was 45 minutes, which was conducted once a week. The primary outcome was sleep disturbance assessed with Pittsburgh Sleep Quality Index (PSQI). Data were analyzed using SPSS software version 19. RESULTS: Eleven patients were assigned to each group. Two groups were matched according to demographic characteristics (age, marital status, education, and daily methadone doses). Although PSQI score was significantly reduced during weeks 5 and 8 after both interventions, there was a significant difference in intervention versus time interaction (P<0.02). The effects of CBTI versus placebo were significantly different (P<0.001). The time course was also significant (P<0.001). CONCLUSION: This study showed that CBTI is more effective than BPT in overall sleep quality. We recommend further studies, with a larger sample, on CBTI in patients undergoing MMT. PMID- 26379346 TI - Oxford Shoulder Score: A Cross-Cultural Adaptation and Validation Study of the Persian Version in Iran. AB - BACKGROUND: Oxford shoulder score is a specific 12-item patient-reported tool for evaluation of patients with inflammatory and degenerative disorders of the shoulder. Since its introduction, it has been translated and culturally adapted in some Western and Eastern countries. The aim of this study was to translate the Oxford Shoulder Score (OSS) in Persian and to test its validity and reliability in Persian speaking population in Iran. METHODS: One hundred patients with degenerative or inflammatory shoulder problem participated in the survey in 2012. All patients completed the Persian version of OSS, Persian DASH and the SF-36 for testing validity. Randomly, 37 patients filled out the Persian OSS again three days after the initial visit to assess the reliability of the questionnaire. RESULTS: Cronbach's alpha coefficient was 0.93. The intraclass correlation coefficient was 0.93. In terms of validity, there was a significant correlation between the Persian OSS and DASH and SF-36 scores (P < 0.001). CONCLUSION: The Persian version of the OSS proved to be a valid, reliable, and reproducible tool as demonstrated by high Cronbach's alpha and Pearson's correlation coefficients. The Persian transcript of OSS is administrable to Persian speaking patients with shoulder condition and it is understandable by them. PMID- 26379347 TI - QuantiFERON-TB Gold and Tuberculin Skin Test for the Diagnosis of Latent Tuberculosis Infection in Children. AB - BACKGROUND: Appropriate diagnosis and treatment of latent tuberculosis infection (LTBI) play the most important role in the control of tuberculosis. This study aimed to determine the prevalence of LTBI among healthy tuberculosis unexposed children vaccinated with BCG using the tuberculin skin test (TST) and QuantiFERON TB Gold In-Tube (QFT-GIT) and comparing the agreement between the two tests. METHODS: A cross-sectional study was carried out between October 2009 and March 2010 in 24 schools and 11 daycare centers. A total of 967 children were divided into 15 age groups, with a minimum of 64 children per group. RESULTS: The prevalence rates of LTBI with TST were 3.8%, and 2.2% with QFT-GIT. One case was positive in TST and QFT-GIT, 20 cases were QFT-GIT positive, but TST negative and 36 cases were TST positive, but QFT-GIT negative, and finally, 910 cases were negative in both. There was poor agreement between TST and QFT-GIT (1.8%, 95%, CI: 0%-5.3%, k=0.007). The specificity of QFT-GIT in the BCG vaccinated, children aged 1-15 years old, was 97.8% (97.8%, 95% CI: 96.8%-98.8%). After three months, 2/17 (11.8%) of those initially QFT-GIT negative converted, and 10/15 (66%) of those initially QFT-GIT positive reverted. CONCLUSION: It seems that TST and QFT GIT are not appropriate tests for the diagnosis of LTBI among healthy tuberculosis unexposed BCG vaccinated children. There was a low reproducibility rate of QFT-GIT. The cause of the the poor agreement requires further studies. PMID- 26379348 TI - Cementless Hip Arthroplasty in Southern Iran, Midterm Outcome and Comparison of Two Designs. AB - BACKGROUND: Cementless hip prosthesis was designed to provide biologic fixation, without the use of cement. The second generation components have shown more reliable bone ingrowths and survival rates. We are reporting a midterm result of two designs of cementless prosthesis in a unique culture with different social habits and expectations. METHODS: 52 primary cementless total hip arthroplasty in 42 patients with the mean age of 48.8 years were retrospectively studied. Two groups of prosthesis had been implanted: Harris-Galante II (HGII) in 15 and Versys-Trilogy (V-T) in 37 hips, both from Zimmer company. The patients were assessed clinically, radiographically and with Harris hip score, SF36, WOMAC, and MACTAR questionnaires, with 65 months (26-136) mean follow-up. RESULTS: All the V T prostheses had survived well. Eight of HG II were revised by the last follow-up in 19-102 months. All had undergone acetabular revision and 2 combined with femoral revision. Broken tines of HGII cups were seen in 4 radiographs. The 65 months overall survival was 96.2% for femoral and 84.6% for acetabular components. 90% had good or excellent Harris hip scores. The functional scores were poorer in the HG II group. Pain relief and improved walking were the two main patients' expectations fulfilled in 97.6% and 92.8%, respectively. CONCLUSIONS: The outcome of cementless total hip arthroplasty (THA) is satisfactory and comparable with the literature based on the results of function and survival of this small comparative group. The use of HGII acetabular component should be abandoned. PMID- 26379349 TI - Totally Transanal Laparo-Endoscopic Single-Site ProctoColectomy-Ileoanal J-Pouch (TLPC-J): An Experimental Study of a Novel Approach. AB - BACKGROUND: The natural orifice transluminal endoscopic surgery (NOTES) has become a commonly considered novel approach in the surgical field. The NOTES provide possibility of operation through the natural orifice and decreases the intentional puncture of the systemic organ and subsequent complications. Totally transanal laparo-endoscopic single-site proctoColectomy-Ileoanal J-Pouch (TLPC-J) is a novel method in minimally invasive surgery for total colectomy. The main goal of this study is to perform this new method on an animal model, to assess probable complication and to resolve probable issues by using patients that are candidate for total colectomy. METHOD: Five dogs were prepared in lithotomy position. The TLPC-I procedure consists of endorectal technique with full thickness rectal dissection starting 1 cm orally from the dentate line above the peritoneal reflection and the proximal bowel was replaced into the abdominal cavity. Afterwards, the TriPort system was inserted in the anal canal and mesentrial resection of the total colon, mobilization of a distal ileal segment and intracorporeal suture of an ileal J-loop was accomplished by this system. An incision in the J-loop was conducted transanally. The J-pouch was created with an Endo-GIA(r) and sutured to the rectal wall. RESULTS: All animals survived and passed stool with clear post operation situation. There was no infection in site of anastomosis. CONCLUSION: The TLPC-I provides the possibility of surgery without abdominal wall incision and decreases post operation complication such as pain, abdominal wound infection and wound dehiscence. This technique increases the quality of life and surgeons can discharge the patients early. PMID- 26379350 TI - The Effects of NDRG2 Overexpression on Cell Proliferation and Invasiveness of SW48 Colorectal Cancer Cell Line. AB - BACKGROUND: Colorectal cancer (CRC) is one of the most common causes of cancer related death in the world. The expression of N-myc downstream-regulated gene 2 (NDRG2) is down-regulated in CRC. The aim of this study was to investigate the effect of NDRG2 overexpression on cell proliferation and invasive potential of SW48 cells. METHODS: SW48 cells were transfected with a plasmid overexpressing NDRG2. After stable transfection, the effect of NDRG2 overexpression on cell proliferation was evaluated by MTT assay. The effects of NDRG2 overexpression on cell migration, invasion and cell motility and matrix metalloproteinase 9 (MMP9) activities were also investigated using matrigel transwell assay, wound healing assay and gelatin zymography, respectively. RESULTS: MTT assay showed that overexpression of NDRG2 caused attenuation of SW48 cell proliferation. Transwell and wound healing assay revealed that NDRG2 overexpression led to inhibition of migration, invasion, and motility of SW48 cells. The overexpression of NDRG2 also reduced the activity of secreted MMP-9. CONCLUSIONS: The results of this study suggest that NDRG2 overexpression inhibits proliferation and invasive potential of SW48 cells, which likely occurs via suppression of MMP-9 activity. PMID- 26379351 TI - How Iranian Medical Trainees Approach their Responsibilities in Clinical Settings; A Grounded Theory Research. AB - BACKGROUND: It seems we are now experiencing "responsibility problems" among medical trainees (MTs) and some of those recently graduated from medical schools in Iran. Training responsible professionals have always been one of the main concerns of medical educators. Nevertheless, there is a dearth of research in the literature on "responsibility" especially from the medical education point of view. Therefore, the present study was carried out with the aim of presenting a theoretical based framework for understanding how MTs approach their responsibilities in educational settings. METHOD: This qualitative study was conducted at Shiraz University of Medical Sciences (SUMS) using the grounded theory methodology. 15 MTs and 10 clinical experts and professional nurses were purposefully chosen as participants. Data was analyzed using the methodology suggested by Corbin and Strauss, 1998. RESULTS: "Try to find acceptance toward expectations", "try to be committed to meet the expectations" and "try to cope with unacceptable expectations" were three main categories extracted based on the research data. Abstractly, the main objective for using these processes was "to preserve the integrity of student identity" which was the core category of this research too. Moreover, it was also found that practically, "responsibility" is considerably influenced by lots of positive and negative contextual and intervening conditions. CONCLUSION: "Acceptance" was the most decisive variable highly effective in MTs' responsibility. Therefore, investigating the "process of acceptance" regarding the involved contextual and intervening conditions might help medical educators correctly identify and effectively control negative factors and reinforce the constructive ones that affect the concept of responsibility in MTs. PMID- 26379352 TI - The Prevalence and Risk Factors of Hepatitis Delta Virus in HIV/HBV Co-Infected Patients in Shiraz, Iran, 2012. AB - Evidence has shown that liver disease caused by hepatitis viruses can be more aggressive and severe in HIV infected subjects. Therefore, the present cross sectional study aimed to evaluate the seroprevalence of HDV infection among HIV/HBV co-infected clients in Shiraz, southwest Iran. In this study, 178 patients co-infected with HBV and HIV individuals were enrolled. The diagnosis of HIV infection was documented based on serological assays. The demographic and complementary data were collected by a questionnaire. HBsAg and HDV Ab were detected by commercial quantitative enzyme linked immunosorbent assay kits according to the manufacturer's instructions. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were also measured. The mean age of the participants was 37.4+/-7.4 years (range 22-63). 175 (98.4 %) patients were male and 3 (1.6 %) were female. Among 178 patients co-infected with HIV/HBV, 35 cases (19.7%, 95% CI: 14%-25%) were anti-HDV? positive and 143 (80.3%) were negative for anti-HDV. HDV exposure in HIV/HBV co-infected patients was associated with blood transfusion (P=0.002, OR: 14.3) and prison history (P=0.01, OR: 2.31) but not with age, marital status, unsafe sex contact, and injection drug abuse. Our data showed a relatively high prevalence of HDV infection in HIV infected population in Shiraz, Iran. The high frequency of HDV Ab in patients with blood transfusion and prison history reveals that HDV transmission occurs more frequently in the parental route than sexual contacts; therefore, blood screening for HDV diagnosis in the high-risk group is recommended. PMID- 26379353 TI - K-ras Mutation in Colorectal Cancer, A Report from Southern Iran. AB - There are very few studies about K-ras mutations in colorectal cancer (CRC) from developing countries such as Iran. It is therefore essential to conduct studies to learn about the molecular signature of such tumors, allowing the determination of an appropriate management plan. In the present study, we aimed to determine the frequency and types of K-ras mutations among patients with CRC in Iran. Formalin-fixed paraffin-embedded specimens of 100 cases of CRC were collected from hospitals affiliated with Shiraz University of Medical Sciences (June 2011 to June 2013). All of the H&E slides were examined and proper slide with a minimum of necrosis and maximum of well-preserved tumor cells (at least 70% tumor in each slide) were selected. Recurrent, metastatic, and post chemotherapy cases were excluded from the study. Mutation of codons 12 and 13 of K-ras gene by PCR was performed, followed by direct sequencing by Sanger method. From 100 eligible cases (55 male and 45 females with mean age of 59 years), 32% had mutant K-ras gene; the most common substitution was 12G>C followed by 12G>A and 13G>A, respectively. It is found that K-ras mutation rate, among the selected population of the southern province of Iran, was as high as 32% (codon 12: 71.8% and in codon 13: 25% and one in both codons: 3.1%). PMID- 26379354 TI - Hereditary Spherocytosis Unmasked by Human Parvovirus B19 Induced Aplastic Crisis in a Family. AB - Human parvovirus (HPV) B19 induced aplastic crisis in a family leading to the diagnosis of hereditary spherocytosis (HS) is a very rare condition being barely reported in the literature. We herein report a 4-year-old girl, her brother, and their mother who all presented with progressive pallor and jaundice after a febrile illness. The HPV B19 was diagnosed using polymerase chain reaction (PCR) and positive serology for specific anti-HPV B19 IgM. They were further diagnosed with having HS. The clinical importance of this report is that in the case of an abrupt onset of unexplained severe anemia and jaundice, one should consider underlying hemolytic anemias mostly hereditary spherocytosis complicated by HPV B19 aplastic crisis. Herein, we report the occurrence of this condition, simultaneously in three members of a family. The distinguished feature of this report is that all affected family members developed some degrees of transient pancytopenia, not only anemia, all simultaneously in the course of their disease. PMID- 26379355 TI - Three Living Fasciola Hepatica in the Biliary Tract of a Woman. AB - Fasciola hepatica (F. hepatica) as a foodborne trematode can occasionally cause hepatobiliary diseases. We report a 67-year-old woman who was referred to our center because of the diagnosis of cholangitis. She was a resident of mountainous area with the history of unsafe water and contaminated vegetables. Endoscopic retrograde cholangiopancreatography (ERCP) was performed as a diagnostic and therapeutic modality for her. Three living F. hepatica was removed from biliary tract with a basket via ERCP. Clinical and laboratory condition of the patient improved after therapy of antibiotics and triclabendazole. PMID- 26379356 TI - Asymptomatic Isolated Retroperitoneal Castleman's Disease: A Case Report. AB - Castleman's disease, giant lymph node hyperplasia, is a kind of benign lymphoproliferative disease with gentle behavior. Its etiology and prevalence are unclear. This rare disease is usually found in mediastinal area asymptomatically and incidentally. It is also rare to see this tumor in the retroperitoneum. In this study, we have introduced a 34-year-old woman who referred just with occasional abdominal pain caused by compressive symptoms. Laboratory findings only reported microcytic anemia (MCH: 18.5, MCV: 63, Hemoglobin 10.2 g/dl). Chest and abdominal X-ray imaging showed no remarkable point. In abdominal ultrasonography, a solid and firm tumor with 12.2*5.3*6.6 cm was reported in patient's retroperitoneum. Patient's surgery was done and the tumor (covered by a fibrous thick capsule, with no bizarre appearance and bleeding) was completely removed. Pathologic examination indicated a Castleman's tumor, type of unicentric and hyaline-vascular. This item had been one of the rare reported items of Castleman's disease in the retroperitoneal space. PMID- 26379357 TI - First recorded eruption of Nabro volcano, Eritrea, 2011. AB - We present a synthesis of diverse observations of the first recorded eruption of Nabro volcano, Eritrea, which began on 12 June 2011. While no monitoring of the volcano was in effect at the time, it has been possible to reconstruct the nature and evolution of the eruption through analysis of regional seismological and infrasound data and satellite remote sensing data, supplemented by petrological analysis of erupted products and brief field surveys. The event is notable for the comparative rarity of recorded historical eruptions in the region and of caldera systems in general, for the prodigious quantity of SO2 emitted into the atmosphere and the significant human impacts that ensued notwithstanding the low population density of the Afar region. It is also relevant in understanding the broader magmatic and tectonic significance of the volcanic massif of which Nabro forms a part and which strikes obliquely to the principal rifting directions in the Red Sea and northern Afar. The whole-rock compositions of the erupted lavas and tephra range from trachybasaltic to trachybasaltic andesite, and crystal hosted melt inclusions contain up to 3,000 ppm of sulphur by weight. The eruption was preceded by significant seismicity, detected by regional networks of sensors and accompanied by sustained tremor. Substantial infrasound was recorded at distances of hundreds to thousands of kilometres from the vent, beginning at the onset of the eruption and continuing for weeks. Analysis of ground deformation suggests the eruption was fed by a shallow, NW-SE-trending dike, which is consistent with field and satellite observations of vent distributions. Despite lack of prior planning and preparedness for volcanic events in the country, rapid coordination of the emergency response mitigated the human costs of the eruption. PMID- 26379358 TI - Verb and sentence production and comprehension in aphasia: Northwestern Assessment of Verbs and Sentences (NAVS). AB - BACKGROUND: Verbs and sentences are often impaired in individuals with aphasia, and differential impairment patterns are associated with different types of aphasia. With currently available test batteries, however, it is challenging to provide a comprehensive profile of aphasic language impairments because they do not examine syntactically important properties of verbs and sentences. AIMS: This study presents data derived from the Northwestern Assessment of Verbs and Sentences (NAVS; Thompson, 2011), a new test battery designed to examine syntactic deficits in aphasia. The NAVS includes tests for verb naming and comprehension, and production of verb argument structure in simple active sentences, with each examining the effects of the number and optionality of arguments. The NAVS also tests production and comprehension of canonical and non canonical sentences. METHODS & PROCEDURES: A total of 59 aphasic participants (35 agrammatic and 24 anomic) were tested using a set of action pictures. Participants produced verbs or sentences for the production subtests and identified pictures corresponding to auditorily provided verbs or sentences for the comprehension subtests. OUTCOMES & RESULTS: The agrammatic group, compared to the anomic group, performed significantly more poorly on all subtests except verb comprehension, and for both groups comprehension was less impaired than production. On verb naming and argument structure production tests both groups exhibited difficulty with three-argument verbs, affected by the number and optionality of arguments. However, production of sentences using three-argument verbs was more impaired in the agrammatic, compared to the anomic, group. On sentence production and comprehension tests, the agrammatic group showed impairments in all types of non-canonical sentences, whereas the anomic group exhibited difficulty primarily with the most difficult, object relative, structures. CONCLUSIONS: Results show that verb and sentence deficits seen in individuals with agrammatic aphasia are largely influenced by syntactic complexity; however, individuals with anomic aphasia appear to exhibit these impairments only for the most complex forms of verbs and sentences. The present data indicate that the NAVS is useful for characterising verb and sentence deficits in people with aphasia. PMID- 26379359 TI - Site-Specific Secretome Map Evidences VSMC-Related Markers of Coronary Atherosclerosis Grade and Extent in the Hypercholesterolemic Swine. AB - A major drawback in coronary atherosclerosis (ATS) research is the difficulty of investigating early phase of plaque growth and related features in the clinical context. In this study, secreted proteins from atherosclerotic coronary arteries in a hypercholesterolemic swine model were characterized by a proteomics approach and their expression was correlated to site-specific ATS stage and extent. A wide coronary artery map of secreted proteins has been obtained in high fat (HF) diet induced ATS swine model and a significantly different expression of many proteins related to vascular smooth muscle cell (VSMC) activation/migration has been identified. Significant associations with ATS stage of HF coronary lesions were found for several VSMC-derived proteins and validated for chitinase 3 like protein 1 (CHI3L1) by tissue immunoexpression. A direct correlation (R(2) = 0.85) was evidenced with intima to media thickness ratio values and ELISA confirmed the higher blood concentrations of CHI3L1 in HF cases. These findings confirmed the pivotal role of VSMCs in coronary plaque development and demonstrated a strong site-specific relation between VSMC-secreted CHI3L1 and lesion grade, suggesting that this protein could be proposed as a useful biomarker for diagnosing and staging of atherosclerotic lesions in coronary artery disease. PMID- 26379361 TI - A Genetic Variant in miRNA-219-1 Is Associated with Risk of Esophageal Squamous Cell Carcinoma in Chinese Kazakhs. AB - BACKGROUND: Esophageal cancer (EC), an aggressive digestive tract malignancy, is one of the leading causes of cancer-related deaths worldwide. Besides environmental risk factors, genetic factors might play a key role in the EC carcinogenesis. The aim of the study is to evaluate the association of miR219-1 single-nucleotide polymorphisms (SNPs) with EC. METHODS: A total of 248 Kazakh esophageal squamous cell carcinoma (ESCC) cases and 300 frequency-matched control subjects were recruited for this study. Genomic DNA was isolated from the samples. The miR-219-1 rs107822G > A and rs213210T > C genotypes were determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Linkage disequilibrium (LD) and haplotype analysis were used to detect the degree of association on miR-219-1 rs107822 and rs213210. Real-time quantitative polymerase chain reaction (qRT-PCR) was performed to detect miR-219 1 expression with miR-219-1 rs107822 polymorphism. RESULT: The SNP rs107822G > A in the miR-219-1 gene decreased the risk of Kazakh ESCC. Furthermore, two miR-219 1 SNPs, namely, rs107822 and rs213210, may tag each other to decrease the risk of Kazakh ESCC. These findings indicated that functional polymorphisms miR-219-1 rs107822G > A might change individual susceptibility to Kazakh ESCC. PMID- 26379360 TI - Noncoding Genomics in Gastric Cancer and the Gastric Precancerous Cascade: Pathogenesis and Biomarkers. AB - Gastric cancer is the fifth most common cancer and the third leading cause of cancer-related death, whose patterns vary among geographical regions and ethnicities. It is a multifactorial disease, and its development depends on infection by Helicobacter pylori (H. pylori) and Epstein-Barr virus (EBV), host genetic factors, and environmental factors. The heterogeneity of the disease has begun to be unraveled by a comprehensive mutational evaluation of primary tumors. The low-abundance of mutations suggests that other mechanisms participate in the evolution of the disease, such as those found through analyses of noncoding genomics. Noncoding genomics includes single nucleotide polymorphisms (SNPs), regulation of gene expression through DNA methylation of promoter sites, miRNAs, other noncoding RNAs in regulatory regions, and other topics. These processes and molecules ultimately control gene expression. Potential biomarkers are appearing from analyses of noncoding genomics. This review focuses on noncoding genomics and potential biomarkers in the context of gastric cancer and the gastric precancerous cascade. PMID- 26379363 TI - Statistical inference for the additive hazards model under outcome-dependent sampling. AB - Cost-effective study design and proper inference procedures for data from such designs are always of particular interests to study investigators. In this article, we propose a biased sampling scheme, an outcome-dependent sampling (ODS) design for survival data with right censoring under the additive hazards model. We develop a weighted pseudo-score estimator for the regression parameters for the proposed design and derive the asymptotic properties of the proposed estimator. We also provide some suggestions for using the proposed method by evaluating the relative efficiency of the proposed method against simple random sampling design and derive the optimal allocation of the subsamples for the proposed design. Simulation studies show that the proposed ODS design is more powerful than other existing designs and the proposed estimator is more efficient than other estimators. We apply our method to analyze a cancer study conducted at NIEHS, the Cancer Incidence and Mortality of Uranium Miners Study, to study the risk of radon exposure to cancer. PMID- 26379362 TI - The Prognostic Role of Red Blood Cell Distribution Width in Coronary Artery Disease: A Review of the Pathophysiology. AB - Red blood cell distribution width (RDW) is a measure of red blood cell volume variations (anisocytosis) and is reported as part of a standard complete blood count. In recent years, numerous studies have noted the importance of RDW as a predictor of poor clinical outcomes in the settings of various diseases, including coronary artery disease (CAD). In this paper, we discuss the prognostic value of RDW in CAD and describe the pathophysiological connection between RDW and acute coronary syndrome. In our opinion, the negative prognostic effects of elevated RDW levels may be attributed to the adverse effects of independent risk factors such as inflammation, oxidative stress, and vitamin D3 and iron deficiency on bone marrow function (erythropoiesis). Elevated RDW values may reflect the intensity of these phenomena and their unfavorable impacts on bone marrow erythropoiesis. Furthermore, decreased red blood cell deformability among patients with higher RDW values impairs blood flow through the microcirculation, resulting in the diminution of oxygen supply at the tissue level, particularly among patients suffering from myocardial infarction treated with urgent revascularization. PMID- 26379364 TI - Female multiple matings and male harassment and their effects on fitness of arrhenotokous Thrips tabaci (Thysanoptera: Thripidae). AB - Although it is generally assumed that one or a few matings are sufficient to maximize female fitness and that mating is generally assumed to be costly to females, multiple matings of females have been reported across a wide and taxonomically diverse set of animals. Here, we investigated female mating frequency and male harassment rate in arrhenotokous Thrips tabaci. In addition, the cost to females of mating, multiple matings, and male harassment to females was evaluated. We found that T. tabaci females mated multiple times during their lifetime and were subjected to a high rate of male harassment at all the ages we tested. Mating was costly to females in terms of reducing longevity and delaying the initiation of egg laying, although mating did not affect the survivorship and longevity of males. Furthermore, continual exposure to males also resulted in a fitness cost to mated females in terms of delayed egg production and reduced fecundity. Virgin females of arrhenotokous thrips produce only male progeny whereas mated females of arrhenotokous thrips produce males from unfertilized eggs and females from fertilized eggs. However, multiple matings did not allow females to fertilize a larger proportion of their eggs to increase the female offspring ratio. Our study demonstrates the conflicts between the occurrence of multiple matings and the cost of sexual activities. This raises questions about the evolution of multiple matings and polyandry in this species. Furthermore, these findings suggest that such phenomena may occur in other animal species and influence the evolution of their mating systems. PMID- 26379366 TI - Improving stopping construction to minimize leakage. AB - The proper sealing of stoppings is an important step in reducing leakage from the intake to the return airways. Leakage and the subsequent loss of ventilation resulting from improperly sealed stoppings can lead to unhealthy and unsafe working conditions. The research presented in this paper investigates the total leakage of a stopping, including air leakage through the stopping, at the stopping perimeter, and through the coalbed. The study also examines sealing considerations for stoppings that are constructed under roof control screen, the effects that wooden wedges had on inhibiting efficient application of polyurethane foam sealant, and airflow leakage through the surrounding coal. The work involved building a stopping in a dead end room of the NIOSH Safety Research Coal Mine and then pressurising the room using compressed air. Stopping leakage was evaluated by measuring air pressure loss in the enclosed room due to the air leakage. Part of the research utilises a diluted soap solution that was applied to the stopping and the surrounding coal to detect air leakage signified by bubble formations. The results show that stopping leakage can be minimised with proper sealing. PMID- 26379365 TI - Male rhesus macaques use vocalizations to distinguish female maternal, but not paternal, kin from non-kin. AB - Recognizing close kin and adjusting one's behavior accordingly (i.e., favor kin in social interactions, but avoid mating with them) would be an important skill that can increase an animals' inclusive fitness. Previous studies showed that philopatric female rhesus macaques (Macaca mulatta) bias their social behavior toward maternal and paternal kin. Benefits gained from selecting kin should, however, not only apply to the philopatric sex, for which the enduring spatial proximity facilitates kin discrimination. Given that dispersal is costly, the dispersing sex may benefit from migrating together with their kin or into groups containing kin. In male rhesus macaques, natal migrants bias their spatial proximity toward familiar male kin rather than familiar non-kin. Here, we set up playback experiments to test if males use the acoustic modality to discriminate familiar female kin from non-kin in a non-sexual context. Males responded differently to the presentation of "coo" calls of related and unrelated females, with their reaction depending on the interaction between kin-line (maternal vs paternal kin) and degree of relatedness (r = 0.5, 0.25). Specifically, males were more likely to respond to close kin compared to more distant kin or unrelated females, with this effect being significant in the maternal, but not paternal kin line. The present study adds to our knowledge of kin recognition abilities of the dispersing sex, suggesting that male rhesus macaques are also able to identify kin using the acoustic modality. We discuss that the probability of response might be affected by the potential benefit of the social partner. PMID- 26379367 TI - Education in Juvenile Detention Facilities in the State of Connecticut: A Glance at the System. AB - The state of Connecticut detained 7,444 children and youth and committed approximately 270 to the Department of Children and Families for out of home placement in the 2007-2008 calendar year. A significant number of children and youth have special education needs that are often unidentified by home school districts. State and federal law mandate the provision of special education and related services to this population. In addition, education of these individuals is imperative as research indicates educational success is a key component for decreasing recidivism (relapse into unlawful activity) rates and providing opportunities toward productive adulthood. The cost of recidivism to detention is not only monetary; criminal misconduct also threatens the safety of society members as well. The Yale University Child Study Center under the auspices of the Connecticut Judicial Branch, Court Support Services Division (CSSD) conducted a situational analysis of the juvenile detention centers and community residential centers. The focus of this analysis was to: (1) describe the educational characteristics of detained children and youth; (2) describe the educational programs currently used in detention and assess whether the educational programming provided is consistent with the framework of the State of Connecticut Department of Education; (3) typify the community of teachers working with students in detention, identify systemic obstacles and/or challenges to educating this population, ascertain the pathways of educational records of detained children and youth; and (4) identify system barriers or challenges to delivering education to this population and teaching in detention or alternative to detention settings. This report is a summary of findings. PMID- 26379368 TI - Psychometric Evaluation of the Brief Infant-Toddler Social and Emotional Assessment (BITSEA) in a Predominately Hispanic, Low-Income Sample. AB - The goal of the present study was to evaluate the psychometric properties of the Brief Infant-Toddler Social and Emotional Assessment (BITSEA) with 12- to 15 month-old infants from predominately Hispanic, low-income families. Mothers of 144 infants were screened at a pediatric clinic as part of a larger study examining a brief home-based intervention for infants at-risk for behavior problems. Reliability was good for the BITSEA problem scale in all analyses and acceptable for the BITSEA competence scale in most analyses. Discriminative validity was supported by scores on the BITSEA competence scale significantly predicting delayed status on all ASQ-3 subscales. BITSEA problem scale scores significantly predicted scores on the total problems scale of the Child Behavior Checklist, supporting predictive validity. Analyses revealed a main effect of group on BITSEA problem scale scores, providing preliminary support for sensitivity to change for the BITSEA problem scale. Results support the BITSEA as an effective screening tool for use with young infants, Hispanic and Spanish speaking populations, and low-income families. PMID- 26379369 TI - Does Head Start differentially benefit children with risks targeted by the program's service model? AB - Data from the Head Start Impact Study (N = 3540) were used to test for differential benefits of Head Start after one program year and after kindergarten on pre-academic and behavior outcomes for children at risk in the domains targeted by the program's comprehensive services. Although random assignment to Head Start produced positive treatment main effects on children's pre-academic skills and behavior problems, residualized growth models showed that random assignment to Head Start did not differentially benefit the pre-academic skills of children with risk factors targeted by the Head Start service model. The models showed detrimental impacts of Head Start for maternal-reported behavior problems of high-risk children, but slightly more positive impacts for teacher reported behavior. Policy implications for Head Start are discussed. PMID- 26379371 TI - Political dimensions of 'the psychosocial': The 1948 International Congress on Mental Health and the Mental Hygiene Movement. AB - The Foucauldian sociologist Nikolas Rose has influentially argued that psychosocial technologies have offered means through which the ideals of democracy can be made congruent with the management of social life and the government of citizens in modern Western liberal democracies. This interpretation is contested here through an examination of the 1948 International Congress on Mental Health held in London and the mental hygiene movement that organised it. It is argued that, in Britain, this movement's theory and practice represents an uneasy and ambiguous attempt to reconcile visions of 'the modern' with 'the traditional'. The mental hygienist emphasis on the family is central. Here it appears as a forcing-house of the modern self-sustaining individual. Mental hygienists cast the social organisation of 'traditional' communities as static, with rigid authority frustrating both social progress and the full emergence of individual personality. Yet mental hygienists were also concerned about threats to social cohesion and secure personhood under modernity. If the social organisation of 'traditional' communities was patterned by the archetype of the family, with its personal relations of authority, mental hygienists compressed these relations into the 'private' family. Situated here they became part of a developmental process of mental adjustment through which 'mature', responsible citizens emerged. This reformulation of the family's centrality for the social order informed mental hygienist critiques of the growth of state power under existing forms of democracy, as well as suspicion of popular political participation or protest, and of movements towards greater egalitarianism. PMID- 26379370 TI - Parallel functional category deficits in clauses and nominal phrases: The case of English agrammatism. AB - Individuals with agrammatic aphasia exhibit restricted patterns of impairment of functional morphemes, however, syntactic characterization of the impairment is controversial. Previous studies have focused on functional morphology in clauses only. This study extends the empirical domain by testing functional morphemes in English nominal phrases in aphasia and comparing patients' impairment to their impairment of functional morphemes in English clauses. In the linguistics literature, it is assumed that clauses and nominal phrases are structurally parallel but exhibit inflectional differences. The results of the present study indicated that aphasic speakers evinced similar impairment patterns in clauses and nominal phrases. These findings are consistent with the Distributed Morphology Hypothesis (DMH), suggesting that the source of functional morphology deficits among agrammatics relates to difficulty implementing rules that convert inflectional features into morphemes. Our findings, however, are inconsistent with the Tree Pruning Hypothesis (TPH), which suggests that patients have difficulty building complex hierarchical structures. PMID- 26379372 TI - Transcriptional Regulatory Network for the Development of Innate Lymphoid Cells. AB - Recent studies on innate lymphoid cells (ILCs) have expanded our knowledge about the innate arm of the immune system. Helper-like ILCs share both the "innate" feature of conventional natural killer (cNK) cells and the "helper" feature of CD4(+) T helper (Th) cells. With this combination, helper-like ILCs are capable of initiating early immune responses similar to cNK cells, but via secretion of a set of effector cytokines similar to those produced by Th cells. Although many studies have revealed the functional similarity between helper-like ILCs and Th cells, some aspects of ILCs including the development of this lineage remain elusive. It is intriguing that the majority of transcription factors involved in multiple stages of T cell development, differentiation, and function also play critical roles during ILC development. Regulators such as Id2, GATA-3, Nfil3, TOX, and TCF-1 are expressed and function at various stages of ILC development. In this review, we will summarize the expression and functions of these transcription factors shared by ILCs and Th cells. We will also propose a complex transcriptional regulatory network for the lineage commitment of ILCs. PMID- 26379373 TI - Oral Hygiene Facilitators and Barriers in Greek 10 Years Old Schoolchildren. AB - AIM: The aim of this study was to determine the oral hygiene facilitators and barriers for 10 years old Greek children, via a questionnaire and clinical examination. MATERIALS AND METHODS: This was a cross-sectional study of 266, 10 years old, children recruited from schools in 3 locations in Greece. Data were collected via questionnaires and clinical examination. Questionnaires referred to Children's oral hygiene knowledge, behavior and attitude as well as parents' oral hygiene behavior and educational level. Children were clinically examined by two calibrated pediatric dentists using a WHO probe and artificial light to assess dental plaque (hygiene index-HI), gingivitis (simplified gingival index-GIs) and dental caries (DMFT-BASCD criteria). RESULTS: Regarding oral hygiene knowledge, although 80% of the children were literate of the proper means of oral hygiene, only 58.64% brushed their teeth twice daily and 36.84% used dental floss. Children's oral hygiene knowledge was positively correlated with both parental brushing frequency (rho = 0.175, p < 0.05) and educational level (rho = -0.216, p < 0.05). Toothpaste use was reported by 92.11% of the children. Regarding Children's attitude, 62.28% were concerned whether their teeth were clean, with girls showing greater concern than boys (p < 0.001). Their reported beliefs regarding brushing avoidance were boredom (84.06%), low oral health literacy (73.91%) and forgetfulness (56.52%). CONCLUSION: Oral hygiene facilitators were found to be the concern about how clean were their teeth, oral health literacy of both children and parents and toothpaste appeal to children. Oral hygiene barriers were Children's boredom, low oral health literacy, forgetfulness and low socioeconomic level. How to cite this article: Angelopoulou M, Kavvadia K, Oulis C, Reppa C. Oral Hygiene Facilitators and Barriers in Greek 10 Years Old Schoolchildren. Int J Clin Pediatr Dent 2015;8(2):87-93. PMID- 26379374 TI - Comparative Study of Pulp Vitality in Primary and Young Permanent Molars in Human Children with Pulse Oximeter and Electric Pulp Tester. AB - AIM AND OBJECTIVE: The purpose of this study was to compare the pulp testing methods (pulse oximetry and electric pulp test) in primary and young permanent teeth of children. MATERIALS AND METHODS: The study included a total of 155 children aged 4 to 15 years. Twenty children formed control group I. Study group included all healthy, 85 primary 2nd molars in group II and 85 permanent 1st molars in group III. Fifty children needing endodontics treatment formed test group IV. The readings were recorded as true positive (TP), false positive (FP), true negative (TN), false negative (FN). Based on this, the sensitivity, specificity, positive predictive value and negative predictive value were calculated for each method. The results were statistically analyzed using Chi square test. RESULTS: On comparing pulse oximetry with electric pulp test 'p value' was found to be 0.487 and 1.00 for groups 1 and 2 respectively and was statistically not significant. Whereas 'p-value' for groups 3 and 4 was < 0.0001 and 0.003 respectively and was statistically highly significant. CONCLUSION: The present study indicates that pulse oximetry can be used as a routine method for assessing the pulp vitality in primary, young permanent and mature permanent teeth. How to cite this article: Shahi P, Sood PB, Sharma A, Madan M, Shahi N, Gandhi G. Comparative Study of Pulp Vitality in Primary and Young Permanent Molars in Human Children with Pulse Oximeter and Electric Pulp Tester. Int J Clin Pediatr Dent 2015;8(2):94-98. PMID- 26379375 TI - Use of an Extract of Indian Sacred Plant Ocimum sanctum as an Anticariogenic Agent: An in vitro Study. AB - AIM: To analyze the efficacy of three different concentrations of Ocimum sanctum extract against various microorganisms, Streptococcus mutans, Streptococcus mitis, Streptococcus sanguis, Lactobacillus acidophilus. MATERIALS AND METHODS: Ethanolic extract of Ocimum sanctum was prepared by the hot extraction method. The extract was diluted with an inert solvent, dimethyl sulfoxide to obtain 3 different concentrations (2.5, 5 and 10%) of the extract. 0.2% chlorhexidine was used as a positive control and dimethyl sul-foxide was used as a negative control. The extract, along with the controls, was then subjected to microbiological investigation to determine which concentration among the 3 different concentrations of extract gave a wider inhibition zone against S. mutans, S. mitis, S. sanguis, L. acidophilus. The zones of inhibition were measured in millimeters. RESULTS: Ocimum sanctum leaf extract demonstrated maximum antimicrobial activity against microorganisms responsible for dental caries at the 10% concentration level although 5 and 2.5% were also effective. Maximum activity was seen against S. mutans and S. sanguis with 10% extract. CONCLUSION: Ocimum sanctum leaf extract was effective against all the microorganisms. How to cite this article: Pai RK, Bhat SS, Salman A, Chandra J. Use of an Extract of Indian Sacred Plant Ocimum Sanctum as an Anticariogenic Agent: An in vitro Study. Int J Clin Pediatr Dent 2015;8(2):99-101. PMID- 26379376 TI - Children and Parent's Attitude and Preferences of Dentist's Attire in Pediatric Dental Practice. AB - BACKGROUND: Before arrival into doctor's clinic, child might have acquired an impression of a clinical environment and doctor's appearance. Different kind of doctor's attire may evoke different reactions. By understanding children and parent's perception and preferences about dentist's attire, a suitable dress code could be adopted to establish good rapport with children. AIM: To evaluate children and parental perceptions and preferences towards dentist attire. MATERIALS AND METHODS: A questionnaire designed with series of photographs of male and female dental students in different attires was responded by 150 parents aged 29 to 63 years and 150 children aged 9 to 13 years. RESULTS: Seventy percent of children participants (n = 104) and 42% of parents participants (n = 63) favored the traditional white coat attire. However, 58% parents (n = 87) significantly preferred non-white coat attires in comparison to 30% of children (n = 46) (chi(2) = 21.61, p < 0.001). No statistical significant difference was noted among the children and the parents, both favoring the use of protective wear (chi(2) = 0.99 p > 0.05), no-significant association was found between parents and children response to white coat (chi(2) = 0.39, p = 0.53). A highly significant difference was found between the male participants, who favored the male dentist and female participants preferring the female dentist (chi(2) = 47.16, p < 0.001). CONCLUSION: Our study attempted to rule out the stereotyped concept of 'white coat fear' among children, both children and parents favored traditional white coat attire, contrary to popular misconception 'white coat syndrome'. However, use of child friendly attires could be useful in anxious children for better practice management. How to cite this article: Ellore VPK, Mohammed M, Taranath M, Ramagoni NK, Kumar V, Gunjalli G. Children and Parent's Attitude and Preferences of Dentist's Attire in Pediatric Dental Practice. Int J Clin Pediatr Dent 2015;8(2):102-107. PMID- 26379377 TI - Evaluation of Microleakage and Marginal Ridge Fracture Resistance of Primary Molars Restored with Three Restorative Materials: A Comparative in vitro Study. AB - Composite restorations are popular because of their superior esthetics and acceptable clinical performance. But shrinkage is still a drawback. Polymerization shrinkage results in volumetric contraction, leading to deformation of the cusps, microleakage, decrease of marginal adaptation, enamel micro-cracks and postoperative sensitivity. A new class of ring opening resin composite based on silorane chemistry has been introduced with claims of less than 1% shrinkage during polymerization. The present study was conducted to evaluate and compare the ability of low shrink silorane based material, a packable composite and a compomer to resist microleakage in class II restorations on primary molars and evaluate marginal ridge fracture resistance of these materials. Sixty human primary molars were selected. Class II cavities were prepared and the teeth were divided into three groups of twenty each. Groups were as follows group I: low shrink composite resin (Filtek P90). Group II: packable composite (Filtek P60) and Group III: compomer (Compoglass F). Half of the teeth were used for microleakage and the rest for marginal ridge fracture resistance. For microleakage testing, dye penetration method was used with 1% methylene blue dye. Followed by evaluation and grading under stereomicroscope at 10* magnification. Fracture resistance was tested with universal testing machine. It was concluded that low shrink silorane based composite resin showed the least amount of microleakage, whereas compomer showed the highest microleakage. Packable composite resisted fracture of marginal ridge better than other composite resins. Marginal ridge fracture resistance of packable composite was comparable to the intact side. How to cite this article: Yeolekar TS, Chowdhary NR, Mukunda KS, Kiran NK. Evaluation of Microleakage and Marginal Ridge Fracture Resistance of Primary Molars Restored with Three Restorative Materials: A Comparative in vitro Study. Int J Clin Pediatr Dent 2015;8(2):108-113. PMID- 26379378 TI - Comparative Evaluation of the Effects of Fluoride Mouthrinse, Herbal Mouthrinse and Oil Pulling on the Caries Activity and Streptococcus mutans Count using Oratest and Dentocult SM Strip Mutans Kit. AB - BACKGROUND: As the technological level of healthcare increases, it is important not to lose sight of the basics of patient care. No matter how sophisticated dental techniques have become, preventive dentistry still remains the foundation for oral health. Therefore, antimicrobial mouthrinses are developed to provide an effective means of preventing colonization by micro-organisms. AIM: The aim of this study was to evaluate and compare the antimicrobial activity of oil pulling, herbal mouthrinses and fluoride mouthwash on the caries activity and S. mutans counts in the saliva of children, using Oratest and Dentocult SM kit. DESIGN: Fifty-two healthy children between the age group of 6 to 12 years were selected for the study and divided into four groups based on the mouthrinse used as group 1: fluoride, group 2: herbal, group 3: oil pulling and group 4: control. The estimation of caries activity and S. mutans was done prior to and after the subjects were instructed to use the mouthrinse twice daily for a period of 2 weeks. STATISTICAL ANALYSIS: The comparisons were made by applying paired 't' test with the level of significance set at p < 0.05. Difference between more than two mean values was done by using ANOVA and Post hoc Bonferroni test was used for multiple comparisons. RESULTS AND CONCLUSION: The efficacy of fluoride and herbal mouthrinses was found to be comparable while oil pulling did not provide any additional benefit to be used as an effective antimicrobial agent in reducing the bacterial colonization of an individual. How to cite this article: Jauhari D, Srivastava N, Rana V, Chandna P. Comparative Evaluation of the Effects of Fluoride Mouthrinse, Herbal Mouthrinse and Oil Pulling on the Caries Activity and Streptococcus mutans Count using Oratest and Dentocult SM Strip Mutans Kit. Int J Clin Pediatr Dent 2015;8(2):114-118. PMID- 26379379 TI - Efficacy of Different Precooling Agents and Topical Anesthetics on the Pain Perception during Intraoral Injection: A Comparative Clinical Study. AB - Topical anesthesia is widely advocated in pediatric dentistry practice to reduce pain and anxiety produced by administration of local anesthesia. Cryoanesthesia to lessen the injection pain has also been reported to be promising. However, sparse literature reports exist regarding clinical efficacy of these agents. AIM: The purpose of this study was to compare the efficacy of the refrigerant (1,1,1,3,3-pentafluoropropane/1,1,1,2-tetrafluo-roethane), benzocaine and ice on the pain perception during intraoral injection using visual analog scale (VAS) and sound, eye, motor (SEM) scale. STUDY DESIGN: In this Spit-mouth design study, a total of 160 patients between the age group of 5 and 8 years were selected and were randomly divided into two equal groups having 80 patients in each group. RESULTS: Ice cone has shown lower mean scores (p < 0.001) as compared to benzocaine and refrigerant whereas no significant difference was observed between refrigerant and benzocaine (p > 0.05) on both the scales. CONCLUSION: Ice cone had shown significantly higher efficacy as compared to benzocaine and refrigerant. How to cite this article: Lathwal G, Pandit IK, Gugnani N, Gupta M. Efficacy of Different Precooling Agents and Topical Anesthetics on the Pain Perception during Intraoral Injection: A Comparative Clinical Study. Int J Clin Pediatr Dent 2015;8(2):119-122. PMID- 26379380 TI - Effect of Conventional and Game-based Teaching on Oral Health Status of Children: A Randomized Controlled Trial. AB - AIM: To compare the effectiveness of conventional and game-based teaching on the level of knowledge and practice regarding oral hygiene among 7 to 10-year-old school children. MATERIALS AND METHODS: A total of 60 children aged 8 to 10 years were randomly divided into two groups: groups A and B. The intervention was started after the pretest evaluation of their knowledge regarding oral health and estimation of Debris Index-simplified (DI-S). Children in group A were given oral health education through flash cards once daily for 7 days. Children in group B were educated through the play-way method, i.e. connect the dots game combined with flash cards. The evaluations, regarding oral hygiene and DI-S were recorded on the 8th day after intervention. A follow-up score was also recorded after 1 and 3 months. Statistical analysis was done using paired t-test and Chi-square test. RESULTS: There was significant increase in oral hygiene scores and decrease in debris scores compared to baseline in both groups at 1 week and 1 month. At 3 months interval, both groups showed a decrease in oral hygiene scores from baseline with group B showing highly significant reduction. The mean increase in knowledge score was also significantly better in group B (p < 0.05). CONCLUSION: The connect the dots game that includes oral health guidelines including good dental hygiene and dietary habits can thus be an effective intervention aid for teaching the basic oral health concepts among school going children. How to cite this article: Kumar Y, Asokan S, John B, Gopalan T. Effect of Conventional and Game-based Teaching on Oral Health Status of Children: A Randomized Controlled Trial. Int J Clin Pediatr Dent 2015;8(2):123-126. PMID- 26379381 TI - Management of Symphysis and Parasymphysis Mandibular Fractures in Children Treated with MacLennan Splint: Stability and Early Results. AB - OBJECTIVE: The aim of this study was to assess the safety and efficiency of MacLennan splint in symphysis and parasymphysis mandibular fractures in children. STUDY DESIGN: Six patients (four boys and two girls, mean age 3 years, range between 2 and 5 years) were operated on parasymphysis fractures of children. The mean follow-up time was 12 months. MacLennan splint was applied in these case upto 3 weeks. RESULTS: Primary healing of the fractured mandible was observed in all patients. Postoperative complications were minor and transient. The outcome of the operation was not endangered. Adverse tissue reaction like infection, malocclusion, swelling and growth restrictions did not occur during observation period. CONCLUSION: MacLennan splint is having various advantages like faster mobilization and the avoidance of secondary removal operations. Based on this preliminary results MacLennan splints are safe and efficient in the treatment of pediatric mandible fracture. How to cite this article: Khairwa A, Bhat M, Sharma A, Sharma R. Management of Symphysis and Parasymphysis Mandibular Fractures in Children Treated with MacLennan Splint: Stability and Early RESULTS. Int J Clin Pediatr Dent 2015;8(2):127-132. PMID- 26379382 TI - Treatment of Large Periapical Cyst Like Lesion: A Noninvasive Approach: A Report of Two Cases. AB - Periapical lesions develop as sequelae to pulp disease. Periapical radiolucent areas are generally diagnosed either during routine dental radiographic examination or following acute toothache. Various methods can be used in the nonsurgical management of periapical lesions: the conservative root canal treatment, decompression technique, active nonsurgical decompression technique, aspiration-irrigation technique, method using calcium hydroxide, lesion sterilization and repair therapy and the apexum procedure. Monitoring the healing of periapical lesions is essential through periodic follow-up examinations. The ultimate goal of endodontic therapy should be to return the involved teeth to a state of health and function without surgical intervention. All inflammatory periapical lesions should be initially treated with conservative nonsurgical procedures. Surgical intervention is recommended only after nonsurgical techniques have failed. Besides, surgery has many drawbacks, which limit its use in the management of periapical lesions. How to cite this article: Sood N, Maheshwari N, Gothi R, Sood N. Treatment of Large Periapical Cyst Like Lesion: A Noninvasive Approach: A Report of Two Cases. Int J Clin Pediatr Dent 2015;8(2):133-137. PMID- 26379383 TI - Treatment of Oroantral Fistula in Pediatric Patient using Buccal Fat Pad. AB - Brief background: Oroantral communication (OAC) is the space created between the maxillary sinus and the oral cavity, which, if not treated, will progress to oroantral fistula (OAF). Several methods of surgical OAC repair have been described, but only a few have gained recognition. MATERIALS AND METHODS: A 13 years old male child patient with complaint of difficulty in drinking water and change in voice diagnosed as OAF managed with closure with buccal fat pad (BFP). DISCUSSION: Oroantral fistula is an abnormal communication resulting most frequently from extraction of the upper posterior teeth. Many techniques have been proposed for the closure. The preferred technique may vary from one surgeon to another. CONCLUSION: The adequate availability of BFP in children, effortless mobilization excellent blood supply and minimal donor site morbidity make it a perfect flap for OAF closure in pediatric patient. How to cite this article: Agrawal A, Singhal R, Kumar P, Singh V, Bhagol A. Treatment of Oroantral Fistula in Pediatric Patient using Buccal Fat Pad. Int J Clin Pediatr Dent 2015;8(2):138 140. PMID- 26379384 TI - Oral and Dental Considerations in Management of Sickle Cell Anemia. AB - Sickle cell anemia is a genetic disease that primarily affects the black population. This anemia is due to a homozygous state of the abnormal hemoglobin S. An alteration occurs on the DNA molecule involving the substitution of the amino acid valine for glutamic acid at the sixth position on the beta polypeptide chain. This biochemical variation on the DNA molecule creates a physiological change that causes sickle-shaped red blood cells to be produced. The sickle shaped cells are the result of the hemoglobin S being deoxygenated. This case report presents a case of 16-year-old female with sickle cell disease and its dental management. How to cite this article: Acharya S. Oral and Dental Considerations in Management of Sickle Cell Anemia. Int J Clin Pediatr Dent 2015;8(2):141-144. PMID- 26379385 TI - Surgical Retrieval of Tooth Fragment from Lower Lip and Reattachment after 6 Months of Trauma. AB - Dental traumas are one of the most frequent facial traumas especially in children. Maxillary incisors are the most frequently involved teeth. Here we present, a report of a child who sustained a crown fracture with lost portion of tooth embedded in her lower lip for 6 months. The fragment was surgically retrieved and successfully reattached to the fractured 21 using acid-etch resin technique. How to cite this article: Marwaha M, Bansal K, Srivastava A, Maheshwari N. Surgical Retrieval of Tooth Fragment from Lower Lip and Reattachment after 6 Months of Trauma. Int J Clin Pediatr Dent 2015;8(2):145-148. PMID- 26379386 TI - Robinow Syndrome: A Rare Case Report and Review of Literature. AB - Robinow syndrome is an extremely rare genetic disorder. Short-limbed dwarfism, abnormalities in the head, face, and external genitalia, as well as vertebral defects comprise its distinct features. This disorder exists in dominant and recessive patterns. Patients with the dominant pattern exhibit moderate symptoms. More physical characteristics and skeletal abnormalities characterize the recessive group. The syndrome is also known as Robinow-Silverman-Smith syndrome, Robinow dwarfism, fetal face, fetal face syndrome, fetal facies syndrome, acral dysostosis with facial and genital abnormalities, or mesomelic dwarfism-small genitalia syndrome. Covesdem syndrome was the name entitled for the recessive form previously. Here, we report a case of 8-year-old female with a autosomal recessive Robinow syndrome having skeletal and vertebral defects. How to cite this article: Soman C, Lingappa A. Robinow Syndrome: A Rare Case Report and Review of Literature. Int J Clin Pediatr Dent 2015;8(2):149-152. PMID- 26379387 TI - Adverse Reaction of Sodium Hypochlorite during Endodontic Treatment of Primary Teeth. AB - Sodium hypochlorite (NaOCl) is the most common and effective intracanal medicament used in root canal treatments, because of its low-cost and a very effective antimicrobial activity against microbiota of infected root canals. Sodium hypochlorite is an effective intracanal irrigant and is used in concentrations ranging from 0.5 to 5.25%. At these concentrations, it is highly hypertonic and strongly alkaline with pH 11 to 13. Despite its safe properties, serious complications can result from inadvertent use due to its cytotoxic features. Most of the complications are the result of accidental extrusion of the solution from the apical foramen or accessory canals or perforations into the periapical area. Although it is an effective solution for disinfection of root canal system, fewer incidence of complications are reported, especially in primary teeth. Present article highlights one of such cases of NaOCl accident and its successful management in a 4-year-old child. How to cite this article: Chaugule VB, Panse AM, Gawali PN. Adverse Reaction of Sodium Hypochlorite during Endo-dontic Treatment of Primary Teeth. Int J Clin Pediatr Dent 2015;8(2):153 156. PMID- 26379388 TI - Dental Treatment of a Child Suffering from Non-bullous Congenital Ichthyosiform Erythroderma under General Anesthesia. AB - Non-bullous congenital ichthyosiform erythroderma (NBCIE) is an autosomal recessive form of inherited icthyosis appears as fine white scales that gradually replace collodion membrane. This case report describes management of 5 years and 11-month-old child with NBCIE suffering from early childhood caries (ECC) under general anesthesia. How to cite this article: Choudhary R, Satish V. Dental Treatment of a Child Suffering from Non-bullous Congenital Ichthyosiform Erythroderma under General Anesthesia. Int J Clin Pediatr Dent 2015;8(2):157-162. PMID- 26379389 TI - A Rare Case Report of Neurodegenerative Disease: Duchenne Muscular Dystrophy in Two Male Siblings. AB - Duchenne muscular dystrophy (DMD) is an recessive X-linked mediated, musculoskeletal disorder that affects only males. It is the most common and severe form of muscular dystrophy where there is failure to manufacture dystrophin. Clinically, it is characterized by progressive muscle wasting eventually leading to premature death. This case report describes the genetic, oral and systemic findings in two cases of DMD in male siblings. How to cite this article: Suneja B, Suneja ES, Adlakha VK, Chandna P. A Rare Case Report of Neurodegenerative Disease: Duchenne Muscular Dystrophy in Two Male Siblings. Int J Clin Pediatr Dent 2015;8(2):163-165. PMID- 26379390 TI - International guidelines for the management of pancreatic intraductal papillary mucinous neoplasms. AB - The management of intraductal papillary mucinous neoplasms (IPMN) is presently evolving as a result of the improved understanding of the natural history and biological behavior of the different pancreatic cystic neoplasms; and better preoperative diagnosis of these neoplasms due to advancement in preoperative diagnostic tools. International consensus guidelines for the management of IPMN were first formulated in 2006 and subsequently revised in 2012. Both these guidelines were constructed based on expert opinion and not on robust clinical data. The main limitation of the original Sendai guidelines was that it had a low positive predictive value resulting in many benign neoplasms being resected. Hence, these guidelines were revised in 2012. However, although the updated guidelines resulted in an improvement in the positive predictive value over the Sendai Guidelines, the results of several studies validating these guidelines demonstrated that its positive predictive value remained low. Furthermore, although both guidelines were associated with high negative predictive values, several investigators have demonstrated that some malignant IPMNs may be missed. Finally, it is imperative to emphasize that major considerations when managing a patient with IPMN including the patient's surgical risk, life-expectancy and even cost of investigations are not taken into account in current guidelines. The management of a patient with IPMN should be individualized and tailored according to a patient's risk benefit profile for resection vs surveillance. PMID- 26379391 TI - Recent advances in the molecular diagnostics of gastric cancer. AB - Gastric cancer (GC) is the third most common cause of cancer-related death in the world, representing a major global health issue. Although the incidence of GC is declining, the outcomes for GC patients remain dismal because of the lack of effective biomarkers to detect early GC and predict both recurrence and chemosensitivity. Current tumor markers for GC, including serum carcinoembryonic antigen and carbohydrate antigen 19-9, are not ideal due to their relatively low sensitivity and specificity. Recent improvements in molecular techniques are better able to identify aberrant expression of GC-related molecules, including oncogenes, tumor suppressor genes, microRNAs and long non-coding RNAs, and DNA methylation, as novel molecular markers, although the molecular pathogenesis of GC is complicated by tumor heterogeneity. Detection of genetic and epigenetic alterations from gastric tissue or blood samples has diagnostic value in the management of GC. There are high expectations for molecular markers that can be used as new screening tools for early detection of GC as well as for patient stratification towards personalized treatment of GC through prediction of prognosis and drug-sensitivity. In this review, the studies of potential molecular biomarkers for GC that have been reported in the publicly available literature between 2012 and 2015 are reviewed and summarized, and certain highlighted papers are examined. PMID- 26379392 TI - Circulating microRNAs as diagnostic and prognostic tools for hepatocellular carcinoma. AB - Hepatocellular carcinoma (HCC) is an aggressive malignancy and the second leading cause of cancer-related deaths worldwide. Conventional biomarkers exhibit poor performance in the surveillance, diagnosis, and prognosis of HCC. MicroRNAs (miRNAs) are a class of evolutionarily conserved small non-coding RNAs that are involved in the regulation of gene expression and protein translation, and they play critical roles in cell growth, differentiation, and the development of various types of cancers, including HCC. Recent evidence revealed the role of miRNAs as potential novel and ideal biomarkers for HCC. miRNAs are released to extracellular spaces, and they are extremely stable in bodily fluids, including serum or plasma, where they are packaged into various microparticles or associated with RNA-binding proteins. Numerous studies have demonstrated that circulating miRNAs have potential applications as minimally invasive biomarkers for HCC diagnosis and prognosis. The present review highlights current understanding of miRNA biogenesis and the origins and types of circulating miRNAs. We summarize recent progress in the use of circulating miRNAs as diagnostic and prognostic biomarkers for HCC. We also discuss the challenges and perspectives of the clinical utility of circulating miRNAs in HCC. PMID- 26379394 TI - Dexamethasone inhibits hypoxia-induced epithelial-mesenchymal transition in colon cancer. AB - AIM: To elucidate the effects of dexamethasone on hypoxia-induced epithelial-to mesenchymal transition (EMT) in colon cancer. METHODS: Human colon cancer HCT116 and HT29 cells were exposed to normoxic (21%) and hypoxic (1%) conditions. First, the effect of dexamethasone on cell viability was examined by MTT cell proliferation assay. In order to measure the expression levels of EMT markers (Snail, Slug, Twist, E-cadherin, and integrin alphaVbeta6) and hypoxia-related genes [Hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF)] by dexamethasone, quantitative real-time polymerase chain reaction and western blot analysis were performed. Furthermore, the morphological changes of colon cancer cells and the expression pattern of E-cadherin by dexamethasone were detected through immunocytochemistry. Finally, the effects of dexamethasone on the invasiveness and migration of colon cancer cells were elucidated using matrigel invasion, migration, and wound healing migration assays. RESULTS: Under hypoxia, dexamethasone treatment inhibited HIF-1alpha protein level and its downstream gene, VEGF mRNA level in the colon cancer cell lines, HCT116 and HT29. In addition, the presence of dexamethasone down-regulated the mRNA levels of hypoxia-induced Snail, Slug, and Twist, all transcriptional factors of EMT, as well as hypoxia-induced integrin alphaVbeta6 protein level, a well-known EMT marker for colon cancer cells. Furthermore, reduced E-cadherin in hypoxic condition was found to be recoverable by treating with dexamethasone in both colon cancer cell lines. Similarly, under hypoxic conditions, dexamethasone restored the growth pattern and morphological phenotype reminiscent of colon cancer cells grown under normoxic conditions; dexamethasone blocked the migration and invasion of both colorectal cancer cell lines in hypoxia. CONCLUSION: Our study suggested that dexamethasone has inhibitory effects on cell migration and invasion by suppressing EMT of colon cancer cell lines in hypoxic condition. PMID- 26379395 TI - MiR-9a-5p regulates proliferation and migration of hepatic stellate cells under pressure through inhibition of Sirt1. AB - AIM: To reveal the functions of microRNAs (miRNAs) with respect to hepatic stellate cells (HSCs) in response to portal hypertension. METHODS: Primary rat HSCs were exposed to static water pressure (10 mmHg, 1 h) and the pressure induced miRNA expression profile was detected by next-generation sequencing. Quantitative real-time polymerase chain reaction was used to verify the expression of miRNAs. A potential target of MiR-9a-5p was measured by a luciferase reporter assay and Western blot. CCK-8 assay and Transwell assay were used to detect the proliferation and migration of HSCs under pressure. RESULTS: According to the profile, the expression of miR-9a-5p was further confirmed to be significantly increased after pressure overload in HSCs (3.70 +/- 0.61 vs 0.97 +/ 0.15, P = 0.0226), which resulted in the proliferation, migration and activation of HSCs. In vivo, the up-regulation of miR-9a-5p (2.09 +/- 0.91 vs 4.27 +/- 1.74, P = 0.0025) and the down-regulation of Sirt1 (2.41 +/- 0.51 vs 1.13 +/- 0.11, P = 0.0006) were observed in rat fibrotic liver with portal hypertension. Sirt1 was a potential target gene of miR-9a-5p. Through restoring the expression of Sirt1 in miR-9a-5p transfected HSCs on pressure overload, we found that overexpression of Sirt1 could partially abrogate the miR-9a-5p mediated suppression of the proliferation, migration and activation of HSCs. CONCLUSION: Our results suggest that during liver fibrosis, portal hypertension may induce the proliferation, migration and activation of HSCs through the up-regulation of miR-9a-5p, which targets Sirt1. PMID- 26379396 TI - Macrophage migration inhibitory factor as a potential prognostic factor in gastric cancer. AB - AIM: To investigate macrophage migration inhibitory factor (MIF) expression and its clinical relevance in gastric cancer, and effects of MIF knockdown on proliferation of gastric cancer cells. METHODS: Tissue microarray containing 117 samples of gastric cancer and adjacent non-cancer normal tissues was studied for MIF expression by immunohistochemistry (IHC) semiquantitatively, and the association of MIF expression with clinical parameters was analyzed. MIF expression in gastric cancer cell lines was detected by reverse transcription polymerase chain reaction (RT-PCR) and Western blot. Two pairs of siRNA targeting the MIF gene (MIF si-1 and MIF si-2) and one pair of scrambled siRNA as a negative control (NC) were designed and chemically synthesized. All siRNAs were transiently transfected in AGS cells with Oligofectamine(TM) to knock down the MIF expression, with the NC group and mock group (Oligofectamine(TM) alone) as controls. At 24, 48, and 72 h after transfection, MIF mRNA was analyzed by RT PCR, and MIF and proliferating cell nuclear antigen (PCNA) proteins were detected by Western blot. The proliferative rate of AGS cells was assessed by methylthiazolyl tetrazolium (MTT) assay and colony forming assay. RESULTS: The tissue microarray was informative for IHC staining, in which the MIF expression in gastric cancer tissues was higher than that in adjacent non-cancer normal tissues (P < 0.001), and high level of MIF was related to poor tumor differentiation, advanced T stage, advanced tumor stage, lymph node metastasis, and poor patient survival (P < 0.05 for all). After siRNA transfection, MIF mRNA was measured by real-time PCR, and MIF protein and PCNA were assessed by Western blot analysis. We found that compared to the NC group and mock group, MIF expression was knocked down successfully in gastric cancer cells, and PCNA expression was downregulated with MIF knockdown as well. The cell counts and the doubling times were assayed by MTT 4 d after transfection, and colonies formed were assayed by colony forming assay 10 d after transfection; all these showed significant changes in gastric cancer cells transfected with specific siRNA compared with the control siRNA and mock groups (P < 0.001 for all). CONCLUSION: MIF could be of prognostic value in gastric cancer and might be a potential target for small-molecule therapy. PMID- 26379393 TI - Circulating microRNAs and long non-coding RNAs in gastric cancer diagnosis: An update and review. AB - Gastric cancer (GC) is the fourth most common cancer and the third leading cause of cancer mortality worldwide. MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are the most popular non-coding RNAs in cancer research. To date, the roles of miRNAs and lncRNAs have been extensively studied in GC, suggesting that miRNAs and lncRNAs represent a vital component of tumor biology. Furthermore, circulating miRNAs and lncRNAs are found to be dysregulated in patients with GC compared with healthy individuals. Circulating miRNAs and lncRNAs may function as promising biomarkers to improve the early detection of GC. Multiple possibilities for miRNA secretion have been elucidated, including active secretion by microvesicles, exosomes, apoptotic bodies, high-density lipoproteins and protein complexes as well as passive leakage from cells. However, the mechanism underlying lncRNA secretion and the functions of circulating miRNAs and lncRNAs have not been fully illuminated. Concurrently, to standardize results of global investigations of circulating miRNAs and lncRNAs biomarker studies, several recommendations for pre-analytic considerations are put forward. In this review, we summarize the known circulating miRNAs and lncRNAs for GC diagnosis. The possible mechanism of miRNA and lncRNA secretion as well as methodologies for identification of circulating miRNAs and lncRNAs are also discussed. The topics covered here highlight new insights into GC diagnosis and screening. PMID- 26379397 TI - Development of a rat model of D-galactosamine/lipopolysaccharide induced hepatorenal syndrome. AB - AIM: To develop a practical and reproducible rat model of hepatorenal syndrome for further study of the pathophysiology of human hepatorenal syndrome. METHODS: Sprague-Dawley rats were intravenously injected with D-galactosamine and lipopolysaccharide (LPS) via the tail vein to induce fulminant hepatic failure to develop a model of hepatorenal syndrome. Liver and kidney function tests and plasma cytokine levels were measured after D-galactosamine/LPS administration, and hepatic and renal pathology was studied. Glomerular filtration rate was detected in conscious rats using micro-osmotic pump technology with fluorescein isothiocyanate-labelled inulin as a surrogate marker. RESULTS: Serum levels of biochemical indicators including liver and kidney function indexes and cytokines all significantly changed, especially at 12 h after D-galactosamine/LPS administration [alanine aminotransferase, 3389.5 +/- 499.5 IU/L; blood urea nitrogen, 13.9 +/- 1.3 mmol/L; Cr, 78.1 +/- 2.9 MUmol/L; K(+), 6.1 +/- 0.5 mmol/L; Na(+), 130.9 +/- 1.9 mmol/L; Cl(-), 90.2 +/- 1.9 mmol/L; tumor necrosis factor-alpha, 1699.6 +/- 599.1 pg/mL; endothelin-1, 95.9 +/- 25.9 pg/mL; P < 0.05 compared with normal saline control group]. Hepatocyte necrosis was aggravated gradually, which was most significant at 12 h after treatment with D galactosamine/LPS, and was characterized by massive hepatocyte necrosis, while the structures of glomeruli, proximal and distal tubules were normal. Glomerular filtration rate was significantly decreased to 30%-35% of the control group at 12 h after D-galactosamine/LPS administration [Glomerular filtration rate (GFR)1, 0.79 +/- 0.11 mL/min; GFR2, 3.58 +/- 0.49 mL/min.kgBW(-1); GFR3, 0.39 +/- 0.99 mL/min.gKW(-1)]. The decreasing timing of GFR was consistent with that of the presence of hepatocyte necrosis and liver and kidney dysfunction. CONCLUSION: The joint use of D-galactosamine and LPS can induce liver and kidney dysfunction and decline of glomerular filtration rate in rats which is a successful rat model of hepatorenal syndrome. PMID- 26379398 TI - Neurochemical features of endomorphin-2-containing neurons in the submucosal plexus of the rat colon. AB - AIM: To investigate the distribution and neurochemical phenotype of endomorphin-2 (EM-2)-containing neurons in the submucosal plexus of the rat colon. METHODS: The mid-colons between the right and left flexures were removed from rats, and transferred into Kreb's solution. For whole-mount preparations, the mucosal, outer longitudinal muscle and inner circular muscle layers of the tissues were separated from the submucosal layer attached to the submucosal plexus. The whole mount preparations from each rat mid-colon were mounted onto seven gelatin-coated glass slides, and processed for immunofluorescence histochemical double-staining of EM-2 with calcitonin gene-related peptide (CGRP), choline acetyltransferase (ChAT), nitric oxide synthetase (NOS), neuron-specific enolase (NSE), substance P (SP) and vasoactive intestinal peptide (VIP). After staining, all the fluorescence-labeled sections were observed with a confocal laser scanning microscope. To estimate the extent of the co-localization of EM-2 with CGRP, ChAT, NOS, NSE, SP and VIP, ganglia, which have a clear boundary and neuronal cell outline, were randomly selected from each specimen for this analysis. RESULTS: In the submucosal plexus of the mid-colon, many EM-2-immunoreactive (IR) and NSE-IR neuronal cell bodies were found in the submucosal plexus of the rat mid-colon. Approximately 6 +/- 4.2 EM-2-IR neurons aggregated within each ganglion and a few EM-2-IR neurons were also found outside the ganglia. The EM-2 IR neurons were also immunopositive for ChAT, SP, VIP or NOS. EM-2-IR nerve fibers coursed near ChAT-IR neurons, and some of these fibers were even distributed around ChAT-IR neuronal cell bodies. Some EM-2-IR neuronal cell bodies were surrounded by SP-IR nerve fibers, but many long processes connecting adjacent ganglia were negative for EM-2 immunostaining. Long VIP-IR processes with many branches coursed through the ganglia and surrounded the EM-2-IR neurons. The percentages of the EM-2-IR neurons that were also positive for ChAT, SP, VIP or NOS were approximately 91% +/- 2.6%, 36% +/- 2.4%, 44% +/- 2.5% and 44% +/- 4.7%, respectively, but EM-2 did not co-localize with CGRP. CONCLUSION: EM-2-IR neurons are present in the submucosal plexus of the rat colon and express distinct neurochemical markers. PMID- 26379399 TI - beta-elemene enhances the radiosensitivity of gastric cancer cells by inhibiting Pak1 activation. AB - AIM: To explore the potential of beta-elemene as a radiosensitizer for gastric cancer cells and the underlying mechanisms. METHODS: SGC7901, MKN45, MKN28, N87, and AGS human gastric cancer cell lines were used to screen for radioresistant gastric cancer cell lines. A 3-(4,5-dimeth-ylthiazol-2-yl)-2,5 diphenyltetrazolium (MTT) assay was used to determine the effects of beta-elemene and IPA-3 on cell viability in MKN45 and SGC7901 gastric cancer cell lines. A clonogenic survival assay and annexin V-FITC/PI apoptosis detection assay were used to evaluate cellular radiosensitivity and radiation-induced cell death, respectively. A proteomic method, isobaric tags for relative and absolute quantitation (iTRAQ), was employed to screen the proteins regulated by beta elemene pretreatment prior to ionizing radiation (IR) in SGC7901 gastric cancer cell line. IPA-3 was used as a specific small molecule inhibitor of p21-activated protein kinase 1 (Pak1) to target Pak1 signaling. Protein levels of PAK1IP1 (p21 activated protein kinase-interacting protein 1), total Pak1 (t-Pak1), phospho Pak1 (T423), phospho-ERK1/2 (Thr202/Tyr204), and cleaved caspase-3 (17 kDa) were assessed by western blotting. RESULTS: MKN45 and SGC7901 gastric cancer cell lines were relatively more resistant to IR. beta-elemene pretreatment decreased clonogenic survival following IR in MKN45 and SGC7901 gastric cancer cell lines. Additionally, beta-elemene pretreatment prior to IR increased radiation-induced cell death compared with IR alone in MKN45 (10.4% +/- 0.9% vs 34.8% +/- 2.8%, P < 0.05) and SGC7901 (11.6% +/- 0.9% vs 46.7% +/- 5.2%, P < 0.05) human gastric cancer cell lines, respectively, consistent with the level of cleaved caspase-3 (17 kDa). Through iTRAQ analysis and western blot validation, we found that beta elemene upregulated PAK1IP1 and downregulated phospho-Pak1 (T423) and phospho ERK1/2 in SGC7901 gastric cancer cells. IR increased the level of phospho-Pak1 (T423). Pretreatment with beta-elemene decreased radiation-induced Pak1 and ERK1/2 phosphorylation. Inhibition of Pak1 using IPA-3 decreased clonogenic survival following IR. In addition, IPA-3 increased radiation-induced cell death in MKN45 (13.4% +/- 0.3% vs 26.6% +/- 1.0%, P < 0.05) and SGC7901 (16.0% +/- 0.6% vs 37.3% +/- 1.7%, P < 0.05) gastric cancer cell lines, respectively, consistent with the level of cleaved caspase-3 (17 kDa). Western blotting showed that IPA-3 decreased radiation-induced Pak1 and ERK1/2 phosphorylation. CONCLUSION: This is the first demonstration that beta-elemene enhances radiosensitivity of gastric cancer cells, and that the mechanism involves inhibition of Pak1 signaling. PMID- 26379400 TI - Association of serum gamma-glutamyl transferase with treatment outcome in chronic hepatitis B patients. AB - AIM: To investigate the association of serum gamma-glutamyl transferase (GGT) levels with chronic hepatitis B infection and hepatitis B e antigen (HBeAg) seroconversion. METHODS: A retrospective study was performed on clinical data collected from patients who had been positive for hepatitis B surface antigen for > 6 mo and who were antiviral-treatment naive (n = 215) attending the Hepatitis Clinic at Nanjing Drum Tower Hospital between August 2010 and December 2013. Healthy individuals without liver disease (n = 83) were included as controls. Patients were categorized into four groups based on disease status as recommended by the European Association for the Study of the Liver: immune tolerance (IT; n = 47), HBeAg-positive hepatitis (EPH; n = 93), HBeAg-negative hepatitis (ENH; n = 20), and inactive carrier (IC; n = 55). Prediction of complete response (CR) based on serum GGT was also examined in EPH patients (n = 33) treated for 48 wk with nucleos(t)ide analogue (NA) therapy, including lamivudine plus adefovir combination therapy (n = 20) or entecavir monotherapy (n = 13). CR was defined as a serum hepatitis B virus DNA level < 500 copies/mL and HBeAg seroconversion by 48 wk of treatment. RESULTS: Serum GGT levels were significantly increased in EPH and ENH patients relative to the IT, IC, and healthy control groups (P < 0.01 for all). However, no significant difference in serum GGT levels was found between the EPH and ENH groups. Baseline serum GGT levels were significantly higher in patients who achieved CR (7/33; 21.2%) compared to patients in the non-CR group (26/33; 78.8%; P = 0.011). In addition, the decline in serum GGT was greater in CR patients compared to non-CR patients after 24 wk and 48 wk of treatment (P = 0.012 and P = 0.008, respectively). The receiver operating characteristic curve yielded a sensitivity of 85.71% and a specificity of 61.54% at a threshold value of 0.89 times the upper limit of normal for baseline serum GGT in the prediction of CR following NA therapy. CONCLUSION: Serum GGT is significantly elevated in EPH and ENH patients and is a potential biomarker for the prediction of HBeAg seroconversion following NA therapy. PMID- 26379401 TI - Prognostic significance of the lymphocyte-to-monocyte ratio in patients with metastatic colorectal cancer. AB - AIM: To evaluate the prognostic significance of the lymphocyte to monocyte ratio (LMR) in patients with unresectable metastatic colorectal cancer who received palliative chemotherapy. METHODS: A total of 104 patients with unresectable metastatic colorectal cancer who underwent palliative chemotherapy were enrolled. The LMR was calculated from blood samples by dividing the absolute lymphocyte count by the absolute monocyte count. Pre-treatment LMR values were measured within one week before the initiation of chemotherapy, while post-treatment LMR values were measured eight weeks after the initiation of chemotherapy. RESULTS: The median pre-treatment LMR was 4.16 (range: 0.58-14.06). We set 3.38 as the cut off level based on the receiver operating characteristic curve. Based on the cut off level of 3.38, 66 patients were classified into the high pre-treatment LMR group and 38 patients were classified into the low pre-treatment LMR group. The low pre-treatment LMR group had a significantly worse overall survival rate (P = 0.0011). Moreover, patients who demonstrated low pre-treatment LMR and normalization after treatment exhibited a better overall survival rate than the patients with low pre-treatment and post-treatment LMR values. CONCLUSION: The lymphocyte to monocyte ratio is a useful prognostic marker in patients with unresectable metastatic colorectal cancer who receive palliative chemotherapy. PMID- 26379402 TI - Clinical utility of a new endoscopic scoring system for Crohn's disease. AB - AIM: To evaluate the clinical value of the newly modified Simple Endoscopic Score for Crohn's disease (mSES-CD). METHODS: Seventy-six Crohn's disease (CD) patients who underwent transanal double balloon endoscopy (DBE) in our hospital between 2003 and 2012 were retrospectively reviewed. DBE is defined as small intestinal endoscopy using two attached balloons. We included patients with stenosis which hampered passage of the scope and those who underwent DBE with observation for at least 80 cm from the ileocecal valve. Our new mSES-CD assesses the endoscopic activity of two consecutive small intestinal segments located 0-40 cm and 40-80 cm from the ileocecal valve by DBE, in addition to the activity of four colorectal segments. To compare the usefulness of mSES-CD with SES-CD, we similarly divided the patients into two groups according to total mSES-CD score (low disease activity group, < 4; high disease activity group, >= 4). The clinical value of mSES-CD in predicting clinical outcome in patients with CD was evaluated using the occurrence of surgery after DBE as an endpoint. RESULTS: Median age of the 76 CD patients was 36 years (range, 16-71). Thirty-nine patients had stenosis which hampered passage of the DBE to 80 cm on the proximal side from the ileocecal valve. Median evaluable length of small intestine by DBE was 80 cm (range, 3-200). A total of 74 patients had one or more small intestinal lesions detected by DBE, of which 62 (83.8%) were within 80 cm of the ileocecal valve on the proximal side. Only two patients (2.7%) with proximal-side lesions more than 80 cm from the ileocecal valve did not have lesions within 80 cm. Patients with high mSES-CD scores showed significantly shorter surgery-free survival than those with low scores (P < 0.05). In contrast, surgery-free survival did not significantly differ between the low and high SES-CD groups (P > 0.05). Multivariate analysis by a Cox proportional hazards model identified mSES CD as an independent factor for surgery-free survival. CONCLUSION: mSES-CD is useful in evaluating the risk of surgery-free survival in patients with CD. PMID- 26379404 TI - Detection of gallbladder stones by dual-energy spectral computed tomography imaging. AB - AIM: To evaluate the detectability of gallbladder stones by dual-energy spectral computed tomography (CT) imaging. METHODS: Totally 217 patients with surgically confirmed gallbladder stones were retrospectively analyzed who underwent single source dual-energy CT scanning from August 2011 to December 2013. Polychromatic images were acquired. And post-processing software was used to reconstruct monochromatic (40 keV and 140 keV) images, and calcium-lipid pair-wise base substance was selected to acquire calcium base images and lipid base images. The above 5 groups of images were evaluated by two radiologists separately with 10 year experience in CT image reading. In the 5 groups of images, the cases in the positive group and negative group were counted and then the detection rate was calculated. The inter-observer agreement on the scoring results was analyzed by Kappa test, and the scoring results were analyzed by Wilcoxon test, with P < 0.05 indicating that the difference was statistically significant. The stone detection results of the 5 groups of images were analyzed by chi(2) test. RESULTS: There was good inter-observer agreement (kappa = 0.772). In 217 patients with gallbladder stones, there was a statistically significant difference in stone visualization between spectral images (40 keV, 140 keV, calcium base and lipid base images) and polychromatic images (P < 0.05). 40 keV monochromatic images were better than 140 keV monochromatic images (4.90 +/- 0.35 vs 4.53 +/- 1.15, P < 0.05), and calcium base images were superior to lipid base images (4.91 +/- 0.43 vs 4.77 +/- 0.63, P < 0.05), but there was no statistically significant difference between 40 keV monochromatic images and calcium base images (4.90 +/- 0.35 vs 4.91 +/- 0.43, P > 0.05). In 217 gallbladder stone patients, there were 21, 3, 28, 5 and 12 negative stone cases in polychromatic images, 40 keV images, 140 keV images, calcium base images and lipid base images, respectively, and the differences among the five groups were statistically significant (P < 0.05). CONCLUSION: Monochromatic images and base substance images have a good clinical prospect in the iso-density stone detection. PMID- 26379403 TI - Novel 3-dimensional virtual hepatectomy simulation combined with real-time deformation. AB - AIM: To develop a novel 3-dimensional (3D) virtual hepatectomy simulation software, Liversim, to visualize the real-time deformation of the liver. METHODS: We developed a novel real-time virtual hepatectomy simulation software program called Liversim. The software provides 4 basic functions: viewing 3D models from arbitrary directions, changing the colors and opacities of the models, deforming the models based on user interaction, and incising the liver parenchyma and intrahepatic vessels based on user operations. From April 2010 through 2013, 99 patients underwent virtual hepatectomies that used the conventional software program SYNAPSE VINCENT preoperatively. Between April 2012 and October 2013, 11 patients received virtual hepatectomies using the novel software program Liversim; these hepatectomies were performed both preoperatively and at the same that the actual hepatectomy was performed in an operating room. The perioperative outcomes were analyzed between the patients for whom SYNAPSE VINCENT was used and those for whom Liversim was used. Furthermore, medical students and surgical residents were asked to complete questionnaires regarding the new software. RESULTS: There were no obvious discrepancies (i.e., the emergence of branches in the portal vein or hepatic vein or the depth and direction of the resection line) between our simulation and the actual surgery during the resection process. The median operating time was 304 min (range, 110 to 846) in the VINCENT group and 397 min (range, 232 to 497) in the Liversim group (P = 0.30). The median amount of intraoperative bleeding was 510 mL (range, 18 to 5120) in the VINCENT group and 470 mL (range, 130 to 1600) in the Liversim group (P = 0.44). The median postoperative stay was 12 d (range, 6 to 100) in the VINCENT group and 13 d (range, 9 to 21) in the Liversim group (P = 0.36). There were no significant differences in the preoperative outcomes between the two groups. Liversim was not found to be clinically inferior to SYNAPSE VINCENT. Both students and surgical residents reported that the Liversim image was almost the same as the actual hepatectomy. CONCLUSION: Virtual hepatectomy with real-time deformation of the liver using Liversim is useful for the safe performance of hepatectomies and for surgical education. PMID- 26379405 TI - Clinical comparison of antrum-preserving double tract reconstruction vs roux-en-Y reconstruction after gastrectomy for Siewert types II and III adenocarcinoma of the esophagogastric junction. AB - AIM: To explore a reasonable method of digestive tract reconstruction, namely, antrum-preserving double-tract reconstruction (ADTR), for patients with adenocarcinoma of the esophagogastric junction (AEG) and to assess its efficacy and safety in terms of long-term survival, complications, morbidity and mortality. METHODS: A total of 55 cases were retrospectively collected, including 18 cases undergoing ADTR and 37 cases of Roux-en-Y reconstruction (RY) for AEG (Siewert types II and III) at North Sichuan Medical College. The cases were divided into two groups. The clinicopathological characteristics, perioperative outcomes, postoperative complications, morbidity and overall survival (OS) were compared for the two different reconstruction methods. RESULTS: Basic characteristics including sex, age, body mass index (BMI), Siewert type, pT status, pN stage, and lymph node metastasis were similar in the two groups. No significant differences were found between the two groups in terms of perioperative outcomes (including the length of postoperative hospital stay, operating time, and intraoperative blood loss) and postoperative complications (consisting of anastomosis-related complications, wound infection, respiratory infection, pleural effusion, lymphorrhagia, and cholelithiasis). For the ADTR group, perioperative recovery indexes such as time to first flatus (P = 0.002) and time to resuming a liquid diet (P = 0.001) were faster than those for the RY group. Moreover, the incidence of reflux esophagitis was significantly decreased compared with the RY group (P = 0.048). The postoperative morbidity and mortality rates for overall postoperative complications and the rates of tumor recurrence and metastasis were not significantly different between the two groups. Survival curves plotted using the Kaplan-Meier method and compared by log-rank test demonstrated similar outcomes for the ADTR and RY groups. Multivariate analysis of significantly different factors that presented as covariates on Cox regression analysis to assess the survival and recurrence among AEG patients showed that age, gender, BMI, pleural effusion, time to resuming a liquid diet, lymphorrhagia and tumor-node-metastasis stage were important prognostic factors for OS of AEG patients, whereas the selection of surgical method between ADTR and RY was shown to be a similar prognostic factor for OS of AEG patients. CONCLUSION: ADTR by jejunal interposition presents similar rates of tumor recurrence, metastasis and long-term survival compared with classical reconstruction with RY esophagojejunostomy; however, it offers considerably improved near-term quality of life, especially in terms of early recovery and decreased reflux esophagitis. Thus, ADTR is recommended as a worthwhile digestive tract reconstruction method for Siewert types II and III AEG. PMID- 26379406 TI - Computed tomography and magnetic resonance imaging features of lipid-rich neuroendocrine tumors of the pancreas. AB - AIM: To clarify the computed tomography (CT) and magnetic resonance imaging (MRI) characteristics of lipid-rich pancreatic neuroendocrine tumors (PanNETs). METHODS: Enhanced CT and MRI performed before pancreatectomy in 29 patients with 34 histologically-confirmed PanNETs was retrospectively reviewed. Tumor attenuation on CT and signal intensities on conventional (T1- and T2-weighted) and chemical shift MRI were qualitatively analyzed and compared alongside adipose differentiation-related protein (ADRP) immunostaining (ADRP-positive: lipid-rich; ADRP-negative: non-lipid-rich) results using Fisher's exact test or the Mann Whitney U test. Signal intensity index on chemical shift MRI was quantitatively assessed. RESULTS: There were 15 lipid-rich PanNETs (44.1%) in 12 patients (41.4%). Tumor attenuation during the early, portal venous, and delayed phases of enhanced CT (P = 0.888, 0.443, and 0.359, respectively) and signal intensities on conventional MRI (P = 0.698 and 0.798, respectively) were not significantly different between lipid-rich and non-lipid-rich PanNETs. Four of the 15 lipid rich PanNETs exhibited high signal intensity on subtraction chemical shift MRI, and the association of high signal intensity on subtraction imaging with lipid rich PanNETs was significant (4 of 15 lipid-rich PanNETs, 26.73%, vs 0 of 19 non lipid-rich PanNETs, 0%, P = 0.029). Lipid-rich PanNETs showed a significantly higher signal intensity index than non-lipid-rich PanNETs (0.6% +/- 14.1% vs 10.4% +/- 14.4%, P = 0.004). Eight of 15 lipid-rich PanNETs, vs 0 of 19 non-lipid rich PanNETs, had positive signal intensity index values in concordance with lipid contents. CONCLUSION: CT contrast enhancement and conventional MR signal intensities are similar in lipid-rich and non-lipid-rich PanNETs. Chemical shift MRI can demonstrate cytoplasmic lipids in PanNETs. PMID- 26379407 TI - Accuracy of abdominal auscultation for bowel obstruction. AB - AIM: To investigate the accuracy and inter-observer variation of bowel sound assessment in patients with clinically suspected bowel obstruction. METHODS: Bowel sounds were recorded in patients with suspected bowel obstruction using a Littmann((r)) Electronic Stethoscope. The recordings were processed to yield 25-s sound sequences in random order on PCs. Observers, recruited from doctors within the department, classified the sound sequences as either normal or pathological. The reference tests for bowel obstruction were intraoperative and endoscopic findings and clinical follow up. Sensitivity and specificity were calculated for each observer and compared between junior and senior doctors. Interobserver variation was measured using the Kappa statistic. RESULTS: Bowel sound sequences from 98 patients were assessed by 53 (33 junior and 20 senior) doctors. Laparotomy was performed in 47 patients, 35 of whom had bowel obstruction. Two patients underwent colorectal stenting due to large bowel obstruction. The median sensitivity and specificity was 0.42 (range: 0.19-0.64) and 0.78 (range: 0.35 0.98), respectively. There was no significant difference in accuracy between junior and senior doctors. The median frequency with which doctors classified bowel sounds as abnormal did not differ significantly between patients with and without bowel obstruction (26% vs 23%, P = 0.08). The 53 doctors made up 1378 unique pairs and the median Kappa value was 0.29 (range: -0.15-0.66). CONCLUSION: Accuracy and inter-observer agreement was generally low. Clinical decisions in patients with possible bowel obstruction should not be based on auscultatory assessment of bowel sounds. PMID- 26379408 TI - CTLA-4 and MDR1 polymorphisms increase the risk for ulcerative colitis: A meta analysis. AB - AIM: To evaluate the correlations between cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and multi-drug resistance 1 (MDR1) genes polymorphisms with ulcerative colitis (UC) risk. METHODS: PubMed, EMBASE, Web of Science, Cochrane Library, CBM databases, Springerlink, Wiley, EBSCO, Ovid, Wanfang database, VIP database, China National Knowledge Infrastructure, and Weipu Journal databases were exhaustively searched using combinations of keywords relating to CTLA-4, MDR1 and UC. The published studies were filtered using our stringent inclusion and exclusion criteria, the quality assessment for each eligible study was conducted using Critical Appraisal Skill Program and the resultant high-quality data from final selected studies were analyzed using Comprehensive Meta-analysis 2.0 (CMA 2.0) software. The correlations between SNPs of CTLA-4 gene, MDR1 gene and the risk of UC were evaluated by OR at 95%CI. Z test was carried out to evaluate the significance of overall effect values. Cochran's Q-statistic and I(2) tests were applied to quantify heterogeneity among studies. Funnel plots, classic fail-safe N and Egger's linear regression test were inspected for indication of publication bias. RESULTS: A total of 107 studies were initially retrieved and 12 studies were eventually selected for meta-analysis. These 12 case-control studies involved 1860 UC patients and 2663 healthy controls. Our major result revealed that single nucleotide polymorphisms (SNPs) of CTLA-4 gene rs3087243 G > A and rs231775 G > A may increase the risk of UC (rs3087243 G > A: allele model: OR = 1.365, 95%CI: 1.023-1.822, P = 0.035; dominant model: OR = 1.569, 95%CI: 1.269-1.940, P < 0.001; rs231775 G > A: allele model: OR = 1.583, 95%CI: = 1.306-1.918, P < 0.001; dominant model: OR = 1.805, 95%CI: 1.393-2.340, P < 0.001). In addition, based on our result, SNPs of MDR1 gene rs1045642 C > T might also confer a significant increases for the risk of UC (allele model: OR = 1.389, 95%CI: 1.214-1.590, P < 0.001; dominant model: OR = 1.518, 95%CI: 1.222 1.886, P < 0.001). CONCLUSION: CTLA-4 gene rs3087243 G > A and rs231775 G > A, and MDR1 gene rs1045642 C > T might confer an increase for UC risk. PMID- 26379409 TI - Ligation-assisted endoscopic submucosal resection with circumferential mucosal incision for duodenal carcinoid tumor. AB - Here we present the case of a 64-year-old female with a duodenal carcinoid tumor treated by ligation-assisted endoscopic submucosal resection (ESMR-L) with circumferential mucosal incision (CMI). Band ligation was effective in resecting the duodenal carcinoid tumor after CMI, with an uneventful post-procedural course. Histopathological examination showed clear tumor margins at deeper tissue levels. Thus, in the present case, ESMR-L with CMI was useful for the treatment of duodenal carcinoid tumor. PMID- 26379410 TI - Endoscopic ultrasound-guided biliary drainage: Bilateral systems drainage via left duct approach. AB - Endoscopic ultrasound (EUS)-guided biliary drainage is accepted as a less invasive, alternative treatment for patients in whom endoscopic retrograde cholangiopancreatography has failed. Most patients with malignant hilar obstruction undergo EUS-guided hepaticogastrostomy. The authors present the case of a 77-year-old man with advanced hilar cholangiocarcinoma who had undergone a roux-en-Y hepaticojejunostomy several months prior. He developed progressive jaundice and a low-grade fever that persisted for one week. The enteroscopic assisted endoscopic retrograde cholangiopancreatography failed, thus the patient was scheduled for EUS-guided biliary drainage. In order to obtain adequate drainage, both intrahepatic systems were drained. This report describes the technique used for bilateral drainage via a transgastric approach. Currently, only a few different techniques for EUS-guided right system drainage have been reported in the literature. This case demonstrates that bilateral EUS-guided biliary drainage is feasible and effective in patients with hilar cholangiocarcinoma, and thus can be used as an alternative to percutaneous biliary drainage. PMID- 26379411 TI - Trousseau's syndrome in a patient with advanced stage gastric cancer. AB - Patients with cancer are at high risk for thrombotic events, which are known collectively as Trousseau's syndrome. Herein, we report a 66-year-old male patient who was diagnosed with terminal stage gastric cancer and liver metastasis and who had an initial clinical presentation of upper gastrointestinal bleeding. Acute ischemia of the left lower leg that resulted in gangrenous changes occurred during admission. Subsequent angiography of the left lower limb was then performed. This procedure revealed arterial thrombosis of the left common iliac artery with extension to the external iliac artery, the left common iliac artery, the posterior tibial artery, and the peroneal artery, which were occluded by thrombi. Aspiration of the thrombi demonstrated that these were not tumor thrombi. The interesting aspect of our case was that the disease it presented as arterial thrombotic events, which may correlate with gastric adenocarcinoma. In summary, we suggested that the unexplained thrombotic events might be one of the initial presentations of occult malignancy and that thromboprophylaxis should always be considered. PMID- 26379412 TI - PNPLA3 I148M variant affects non-alcoholic fatty liver disease in liver transplant recipients. AB - De novo non-alcoholic fatty liver disease (NAFLD) is a common late complication for long-term survivors after liver transplantation. Genomic studies confirmed that PNPLA3 I148M and TM6SF2 E167K polymorphisms affected NAFLD susceptibility in the general population. However, this association was not validated in survivors after liver transplantation (LT). We performed a cross-sectional survey to investigate this relationship. A comprehensive survey, including anthropometric measurements, fasting venous blood sampling, ultrasound, and questionnaires was performed in the short-term. The clinical indications and patient's steatosis status before LT were collected from inpatient medical records. Sixty-five long term recipients with a survival exceeding 10 years were enrolled in the final analysis. De novo NAFLD was more frequent in PNPLA3 GG carriers (0.33 vs 0.10 for GG vs CC + CG carriers, P = 0.018), while the genetic impact on NAFLD susceptibility was insignificant when categorized by the TM6SF2 polymorphism (0.19 in CC vs 0.14 in CT + TT carriers, P = 0.883). Multi-covariate analysis revealed that PNPLA3 exerted a significant genetic effect on de novo NAFLD following a recessive model (GG vs CC + CG, OR = 14.2, 95%CI: 1.78-113, P = 0.012). Compared to recipients with only the PNPLA3 GG allele or obesity (defined as body mass index > 25 kg/m(2)), steatosis was highly prevalent (71.4%) in PNPLA3 GG carriers with obesity. In conclusion, PNPLA3 I148M, but not TM6SF2 E167K, affects de novo NAFLD occurrence with a prominent interaction with obesity. Weight control might be a meaningful method to reduce the genetic susceptibility to NAFLD exerted by PNPLA3 variants. PMID- 26379413 TI - Do the benefits of polyandry scale with outbreeding? AB - There have been many potential explanations put forward as to why polyandry often persists despite the multiple costs it can inflict on females. One such explanation is avoidance of costs associated with mating with genetically incompatible males. Genetic incompatibility can be thought of as a spectrum from individuals that are genetically too similar (inbreeding) to those that are too dissimilar (outbreeding or hybridization). Here we look for evidence that the level of outbreeding influences the benefits of polyandry in the seed bug Lygaeus equestris. Our system allows us to test for benefits of polyandry at levels of genetic similarity ranging from full siblings to heterospecifics, both in terms of egg production and hatching success. We found that while outbreeding level appeared to have no effect on fitness for intraspecific matings, and polyandry did not appear to result in any increase in fertility or fecundity, hybridization with a closely related species, Lygaeus simulans, carried considerable fitness costs. However, these costs could be rescued with a single mating to a conspecific. Thus, polyandry may be beneficial in populations that co-occur with closely related species and where there is reproductive interference. However, within-species genetic incompatibility is unlikely to be the driving force behind polyandry in this species. Furthermore, the mechanism underlying this rescue of fertility remains unclear as manipulation of male cuticular hydrocarbon profile, a possible mechanism by which females can assess male identity, had no effect on female offspring production. PMID- 26379414 TI - The Influence of Parental Divorce on Educational Ambitions of 18/19 Year-Old Adolescents from Oslo, Norway. AB - Former studies have shown that children and adolescents of divorced parents have significantly poorer educational attainment than their peers from continuously married parents. Educational ambition is important because it has relationship with educational attainment. Our aim was to investigate the associations between parental divorce and educational ambitions among adolescents in the Scandinavian region. Data were used from Young-HUBRO surveys that were conducted in Oslo in the years 2000/2001 and 2004. A change in educational ambition was investigated in a prospective study (n = 1,861) by comparing 18/19 year-olds who experienced late parental divorce with adolescents of continuously married parents. 18/19 year-old adolescents who experienced parental divorce during childhood or adolescence were compared in a cross-sectional study (n = 2,391) with their peers from continuously married parents. Multinomial logistic regression models were fitted to include, among others, mental health problem as a potential confounder. The prospective study showed that a change from ambition for university/college education to having undecided educational ambition was significantly higher among adolescents with experience of late parental divorce than among adolescents of continuously married parents (OR 1.8; 95 % CI 1.1-3.0). In the cross-sectional study, adolescents who experienced parental divorce during childhood or adolescence were more likely to have undecided educational ambition, compared to their peers from continuously married parents (OR 1.3; 95 % CI 1.1-1.8). In conclusion, experience of parental divorce seems to be associated with undecided educational ambition among 18/19 year-old adolescents. Mechanisms that reduce the adverse influence of parental divorce on educational ambitions need to be in place. PMID- 26379415 TI - Matrix-Similarity Based Loss Function and Feature Selection for Alzheimer's Disease Diagnosis. AB - Recent studies on Alzheimer's Disease (AD) or its prodromal stage, Mild Cognitive Impairment (MCI), diagnosis presented that the tasks of identifying brain disease status and predicting clinical scores based on neuroimaging features were highly related to each other. However, these tasks were often conducted independently in the previous studies. Regarding the feature selection, to our best knowledge, most of the previous work considered a loss function defined as an element-wise difference between the target values and the predicted ones. In this paper, we consider the problems of joint regression and classification for AD/MCI diagnosis and propose a novel matrix-similarity based loss function that uses high-level information inherent in the target response matrix and imposes the information to be preserved in the predicted response matrix. The newly devised loss function is combined with a group lasso method for joint feature selection across tasks, i.e., clinical scores prediction and disease status identification. We conducted experiments on the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset, and showed that the newly devised loss function was effective to enhance the performances of both clinical score prediction and disease status identification, outperforming the state-of-the-art methods. PMID- 26379416 TI - Loop Entropy Assists Tertiary Order: Loopy Stabilization of Stacking Motifs. AB - The free energy of an RNA fold is a combination of favorable base pairing and stacking interactions competing with entropic costs of forming loops. Here we show how loop entropy, surprisingly, can promote tertiary order. A general formula for the free energy of forming multibranch and other RNA loops is derived with a polymer-physics based theory. We also derive a formula for the free energy of coaxial stacking in the context of a loop. Simulations support the analytic formulas. The effects of stacking of unpaired bases are also studied with simulations. PMID- 26379418 TI - BCR-ABL Mutation-Guided Therapy for CML Blast Crisis: A Case Report. AB - The management of patients with chronic myeloid leukemia (CML) in advanced phases is challenging and requires the consideration of different treatment approaches, including targeted therapy with tyrosine kinase inhibitors, cytotoxic chemotherapy, and allogeneic stem cell transplantation. Here, we present the case of a patient with CML in mixed phenotype blast phase illustrating the integration of these strategies and demonstrating the need for close monitoring of treatment response in order to individually adjust treatment regimens. PMID- 26379417 TI - Stem Cells and Progenitor Cells for Tissue-Engineered Solutions to Congenital Heart Defects. AB - Synthetic patches and fixed grafts currently used in the repair of congenital heart defects are nonliving, noncontractile, and not electrically responsive, leading to increased risk of complication, reoperation, and sudden cardiac death. Studies suggest that tissue-engineered patches made from living, functional cells could grow with the patient, facilitate healing, and help recover cardiac function. In this paper, we review the research into possible sources of cardiomyocytes and other cardiac cells, including embryonic stem cells, induced pluripotent stem cells, mesenchymal stem cells, adipose-derived stem cells, umbilical cord blood cells, amniotic fluid-derived stem cells, and cardiac progenitor cells. Each cell source has advantages, but also has technical hurdles to overcome, including heterogeneity, functional maturity, immunogenicity, and pathogenicity. Additionally, biomaterials used as patch materials will need to attract and support desired cells and induce minimal immune responses. PMID- 26379419 TI - Ocular pain and discomfort after advanced surface ablation: an ignored complaint. AB - PURPOSE: Laser vision correction is one of the most commonly performed elective surgical procedures in ophthalmology. Generally, discomfort besides pain (photophobia, burning sensation, tearing, and foreign body sensation) after these procedures is not taken into consideration in the clinical practice. The objective is to provide data on these symptoms and their relevance after advanced surface ablation (ASA). METHODS: Single-center survey study based on a structured questionnaire relative to the patients' perceived symptoms after ASA. Inclusion criteria were: >=18 years old, no ocular disease, with myopia (0.75 to 9 D) or hyperopia (0.25 to 5 D) with or without astigmatism, receiving ASA on at least one eye. All procedures were performed by the same surgeon. A descriptive analysis was performed. RESULTS: Seventy-three consecutive patients (34 men and 39 women) were included in the study. The median (range) of age was 33 (19-64) years. Sixty-nine patients had surgery done on both eyes. Postoperative pain was the most frequent comorbidity (97% [95% confidence interval {CI}: 90-100]) with a median (range) of intensity (verbal numerical rating scale) score of 7 (2-10). Photophobia: 85% (95% CI: 75-92); burning sensation: 62% (95% CI: 50-73); tearing: 59% (95% CI: 47-70); and foreign body sensation: 48% (95% CI: 36-60) were also prevalent postoperative symptoms. Pain during ASA was reported for 44% (95% CI: 32-56) of patients. CONCLUSION: Comorbidities such as pain, photophobia, burning sensation, tearing, and foreign body sensation are prevalent after ASA procedure. Postoperative pain should be taken into consideration due to its prevalence and intensity. A new and more efficient postoperative analgesic protocol should be established. PMID- 26379420 TI - Ocular manifestations and management recommendations of lysosomal storage disorders I: mucopolysaccharidoses. AB - The mucopolysaccharidoses (MPS) are a group of lysosomal storage disorders caused by inborn errors of glycosaminoglycan (GAG) metabolism. These diseases are classified by enzyme deficiency into seven groups: type I, II, III, IV, VI, VII, and IX. GAG accumulation leads to characteristic clinical features. Some ophthalmic findings that are characteristic of MPS diseases include corneal clouding, retinal degeneration, decreased electroretinogram wave amplitude, optic atrophy, papilledema, and glaucoma. Current treatments such as hematopoietic stem cell transplantation and enzyme replacement therapy have increased the life span of many MPS patients and created the need to improve management of ocular symptoms. This article aims to provide a comprehensive review of ocular manifestations and treatment options for the various types of MPS. PMID- 26379421 TI - Does the type of treatment have an influence on utility values in a glaucoma population? AB - PURPOSE: To assess the impact of glaucoma therapy on utility values in a glaucoma population. METHODS: A cross-sectional study of consecutive glaucoma patients was conducted. Utility values were obtained using the time trade-off method. Visual function variables (visual acuity and mean deviation in the better eye) and sociodemographic and clinical characteristics (age, sex, race, educational level, type of glaucoma, current and past glaucoma treatments, and comorbidities) were also obtained for statistical analysis. We divided the patients into three groups: medical treatment (group 1), surgical treatment (group 2), and mixed surgical and medical treatment (group 3). RESULTS: Mean age of the study population (n=225) was 65.7 years. After controlling for glaucoma stage (early, moderate, and advanced), the difference among the groups in mean utility values was not statistically significant. Number of medications per patient, type of medication, or type of surgical technique did not have an impact on the utility values. CONCLUSION: Our findings suggest that the type of therapy did not affect the utility values in a glaucoma population. PMID- 26379422 TI - Repurposing paclitaxel for the treatment of fibrosis: indication discovery for existing drugs. PMID- 26379423 TI - Anthocyanins inhibit high-glucose-induced cholesterol accumulation and inflammation by activating LXRalpha pathway in HK-2 cells. AB - The dysregulation of cholesterol metabolism and inflammation plays a significant role in the progression of diabetic nephropathy (DN). Anthocyanins are polyphenols widely distributed in food and exert various biological effects including antioxidative, anti-inflammatory, and antihyperlipidemic effects. However, it remains unclear whether anthocyanins are associated with DN, and the mechanisms involved in the reciprocal regulation of inflammation and cholesterol efflux are yet to be elucidated. In this study, we evaluated the regulation of cholesterol metabolism and the anti-inflammatory effects exerted by anthocyanins (cyanidin-3-O-beta-glucoside chloride [C3G] or cyanidin chloride [Cy]) and investigated the underlying molecular mechanism of action using high-glucose (HG) stimulated HK-2 cells. We found that anthocyanins enhanced cholesterol efflux and ABCA1 expression markedly in HK-2 cells. In addition, they increased peroxisome proliferator-activated receptor alpha (PPARalpha) and liver X receptor alpha (LXRalpha) expression and decreased the HG-induced expression of the proinflammatory cytokines intercellular adhesion molecule-1 (ICAM1), monocyte chemoattractant protein-1 (MCP1), and transforming growth factor-beta1 (TGFbeta1), as well as NFkappaB activation. Incubation with the PPARalpha specific inhibitor GW6471 and LXRalpha shRNA attenuated the anthocyanin-mediated promotion of ABCA1 expression and cholesterol efflux, suggesting that anthocyanins activated PPARalpha-LXRalpha-ABCA1-dependent cholesterol efflux in HK-2 cells. Moreover, the knockout of LXRalpha abrogated the anti-inflammatory effect of anthocyanins, whereas the PPARalpha antagonist GW6471 does not have this effect. Further investigations revealed that LXRalpha might interfere with anthocyanin-induced decreased ICAM1, MCP1, and TGFbeta1 expression by reducing the nuclear translocation of NFkappaB. Collectively, these findings suggest that blocking cholesterol deposition and inhibiting the LXRalpha pathway-induced inflammatory response might be one of the main mechanisms by which anthocyanins exert their protective effects in DN. PMID- 26379424 TI - The association of CXCR4 expression with clinicopathological significance and potential drug target in prostate cancer: a meta-analysis and literature review. AB - CXCR4/CXCL12 axis plays an important role in tumor growth, angiogenesis, metastasis, and therapeutic resistance. The aim of this study is to perform a meta-analysis and literature review to evaluate the association of CXCR4 expression with clinicopathological significance and prognosis in patients with prostate cancer (PCa). A detailed literature search was made in Medline, EMBASE, Web of Science, and Google Scholar for related research publications. The data were extracted and assessed independently. Analysis of pooled data was performed using Review Manager 5.2. Odds ratio (OR) with corresponding confidence intervals were calculated and summarized. The meta-analysis included a total of eleven studies and 630 patients. The rate of CXCR4 protein expression in PCa was significantly higher than in nonmalignant prostate tissues (OR =35.71, P<0.00001). The expression of CXCR4 protein was not significantly associated with Gleason score (P=0.73). However, the frequency of CXCR4 protein expression was significantly higher in T3-4 stage than in T1-2 stage of PCa (OR =2.35, P=0.001). The expression of CXCR4 protein was significantly associated with the presence of lymph node and bone metastasis of PCa: for lymph node metastasis positive versus negative, OR was 5.07 and P=0.0003, and for bone metastasis positive versus negative, OR was 7.03 and P=0.003. Cancer-specific survival of patients with PCa was significantly associated with CXCR4 protein expression, and the pooled Hazard ratio was 0.24 and P=0.002. In conclusion, the high expression of CXCR4 protein is a diagnostic biomarker of PCa, and it is significantly associated with T stages. The increased expression of CXCR4 protein is significantly associated with lymph nodes or bone metastasis, and CXCR4 is a poor prognosis predictor for patients with PCa. Taken together, our findings indicate that CXCR4 could be a target not only for the development of therapeutic intervention but also for the noninvasive monitoring of PCa progression. PMID- 26379425 TI - Novel synthesizing method of pH-dependent doxorubicin-loaded anti-CD22-labelled drug delivery nanosystem. AB - The objective of this study was to investigate the anticancer efficacy of dimercaptosuccinic acid-modified iron oxide magnetic nanoparticles coloaded with anti-CD22 antibodies and doxorubicin (anti-CD22-MNPs-DOX) on non-Hodgkin's lymphoma cells. The physical properties of anti-CD22-MNPs-DOX were studied and its antitumor effect on Raji cells in vitro was evaluated using the Cell Counting Kit-8 assay. Furthermore, cell apoptosis and intracellular accumulation of doxorubicin were determined by flow cytometry. The results revealed that anti CD22-MNPs-DOX inhibited the proliferation of Raji cells, significantly increased the uptake of doxorubicin, and induced apoptosis. Therefore, it was concluded that a coloaded antibody and chemotherapeutic drug with magnetic nanoparticles might be an efficient targeted treatment strategy for non-Hodgkin's lymphoma. PMID- 26379426 TI - Novel levocetirizine HCl tablets with enhanced palatability: synergistic effect of combining taste modifiers and effervescence technique. AB - OBJECTIVES: Levocetirizine HCl, a second-generation piperazine derivative and H1 selective antihistaminic agent, possesses few side effects. The first objective of the study was to compare and evaluate the taste-masking effect of different ratios of 2-hydroxypropyl-beta-cyclodextrin and mannitol on levocetirizine HCl using an inclusion complex and solid dispersion, respectively. The second objective was to study the possibility of preparing and evaluating effervescent tablets from the best-chosen taste-masked blends for the purpose of their use either as orodispersible tablets or as water-soluble effervescent tablets, according to patients' will. MATERIALS AND METHODS: Prepared taste-masked blends were prepared and subjected to palatability, Fourier-transform infrared spectroscopy, and differential scanning calorimetry studies. Tablets containing different percentages of effervescent mixtures were prepared by direct compression on the selected taste-modified blends. Evaluation tests were conducted, including flowability and compressibility on the precompressed blends and hardness, friability, wetting time, effervescent time, in vitro, in vivo disintegration time, and in vitro dissolution study on the compressed tablets. Formulated tablets were evaluated and compared to marketed orodispersible tablets for mouth feel and palatability. RESULTS: All prepared tablets showed convenient physical and palatability properties compared to the selected brand. The in vitro drug-release study revealed fast release of levocetirizine HCl within 5 minutes from all prepared tablets. CONCLUSION: Levocetirizine HCl effervescent tablets are likely to increase patient compliance with drug administration. Moreover, the use of these effervescent tablets in an orodispersible dosage form can improve oral drug bioavailability and act as an attractive pediatric dosage form. PMID- 26379427 TI - Icariside II ameliorates diabetic nephropathy in streptozotocin-induced diabetic rats. AB - PURPOSE: To investigate the therapeutic effects and potential mechanisms of icariside II (ICA II) on reversing diabetic nephropathy in streptozotocin (STZ) induced type I diabetic rats. METHODS: Newborn male Sprague Dawley rats were labeled with thymidine analog 5-ethynyl-2-deoxyuridine (EdU) for tracking endogenous label retaining progenitor cells (LRCs). At age of 8 weeks, 48 rats were randomly divided into three groups: normal control group (n=16), diabetes mellitus group (DM; n=16), and diabetes mellitus plus ICA II therapy group (DM+ICA II, n=16). Eight weeks induced for diabetes with STZ, rats in DM group and DM+ICA II group were treated with vehicle or ICA II (5 mg/kg/day) for another 8 weeks, respectively. Then, blood creatinine, 24-hour urine protein, blood urea nitrogen, and glycosylated hemoglobin were measured, as well as the expression of von Willebrand factor, malondialdehyde, transforming growth factor beta/drosophila mothers against decapentaplegic protein/connective tissue growth factor (TGF-beta/Smad/CTGF) signaling, marker of proliferation Ki-67, and EdU+ LRCs in renal tissues. RESULTS: Increased levels of creatinine, 24-hour urine protein, and blood urea nitrogen and remarkably decreased proportion of normal glomeruli and increased proportions of I, IIa, IIb, and III glomeruli were observed in diabetic rats, while ICA II could reverse these changes. Interestingly, ICA II could significantly downregulate the levels of malondialdehyde and TGF-beta/Smad/CTGF signaling and increase the expression of von Willebrand factor, Ki-67, and EdU+ LRCs in the kidney. CONCLUSION: ICA II treatment could ameliorate diabetic nephropathy in STZ-induced diabetic rats by increasing endothelial cell contents, downregulating TGF-beta/Smad/CTGF signaling pathway and oxidative stress level, and promoting cell proliferation both in kidney cortex and medulla. These beneficial effects appear to be mediated by its antioxidant capacity and recruitment of endogenous EdU+ progenitor cells into the kidney tissue. PMID- 26379428 TI - Integrated insulin pump therapy with continuous glucose monitoring for improved adherence: technology update. AB - Insulin pump therapy combined with real-time continuous glucose monitoring, known as sensor-augmented pump (SAP) therapy, has been shown to improve metabolic control and to reduce the rate of hypoglycemia in adults with type 1 diabetes compared to multiple daily injections or standard continuous subcutaneous insulin infusion. Glycemic variability is also reduced in patients on SAP therapy. This approach allows patients to monitor their glucose levels being informed of glycemic concentration and trend. Trained diabetic patients, therefore, can appropriately modify insulin infusion and/or carbohydrate intake in order to prevent hypo- or hyperglycemia. For these reasons, SAP therapy is now considered the gold standard for type 1 diabetes treatment. To be clinically effective, however, devices and techniques using advanced technology should not only have the potential to theoretically ameliorate metabolic control, but also be well accepted by patients in terms of satisfaction and health-related quality of life, because these factors will improve treatment adherence and consequently overall outcome. SAP therapy is generally well tolerated by patients; however, many clinical trials have identified significant noncompliance in the use of this device, most notably in the pediatric and adolescent populations. In this review we aim to analyze the main reasons for good or poor adherence to SAP therapy and to provide useful tips in order to fully benefit from this kind of novel therapeutic approach. PMID- 26379429 TI - Transient cerebral ischemia in an elderly patient with patent foramen ovale and atrial septal aneurysm. AB - Cerebrovascular disease is one of the most common causes of cerebrovascular morbidity and mortality in developed countries; up to 40% of acute ischemic strokes in young adults are cryptogenic in nature - that is, no cause is determined. However, in more than half of these patients, patent foramen ovale (PFO) is seen along with an increased incidence of atrial septal aneurysm (ASA). The following is a report of an interesting case: a 68-year-old man with ASA and transient cerebral ischemia. Transesophageal echocardiography (TEE) showed the presence of ASA; a test with microbubbles derived from a mixture of air and saline or colloids pointed out a shunt on the foramen ovale following Valsalva's maneuver. The patient underwent percutaneous transcatheter closure of the interatrial communication by an interventional cardiologist. TEE and transcranial Doppler or TEE with the microbubbles test are the recommended methods for detecting and quantifying intracardiac shunts, both at rest and following Valsalva's maneuver. In patients following the first event of transient ischemic attack, and without clinical and anatomical risk factors (such as the presence of ASA, PFO, and basal shunt), pharmacological treatment with antiplatelets or anticoagulants is closely recommended. On the contrary, in patients following the first event of transient ischemic attack, or a recurrent event during antiplatelet treatment, the percutaneous closure of PFO is recommended. PMID- 26379430 TI - Severe aortic valve stenosis in the elderly: high prevalence of sleep-related breathing disorders. AB - BACKGROUND: Aortic valve stenosis is common in the elderly, with a prevalence of nearly 3% in patients aged 75 years or older. Despite the fact that sleep-related breathing disorders (SRBD) are thought to be associated with cardiac disease, little is known about their prevalence in this patient cohort. The purpose of this study was to evaluate the prevalence of SRBD in older patients with aortic valve stenosis admitted for transcatheter aortic valve implantation. METHODS: Forty-eight consecutive patients (mean age 81+/-6 years; 37.5% male) with symptomatic aortic valve stenosis and considered for transcatheter aortic valve replacement were screened for SRBD. Sleep studies were performed by in-hospital unattended cardiorespiratory polygraphy measuring nasal air flow, chest and abdominal efforts, as well as oxygen saturation and body position. The patients were divided in subgroups dependent on the documented apnea-hypopnea index (AHI; no SRBD was defined as an AHI of <5 events/hour; mild SRBD as AHI 5-15 events/hour, and moderate to severe SRBD as AHI >=15 events/hour). RESULTS: Thirty-seven patients (77%) had SRBD defined as an AHI of >=5 events/hour. Eleven patients had an unremarkable investigation, with AHI <5 events/hour (mean 3.0+/ 1.3 events/hour). Among patients with sleep apnea, 19 patients had mild SRBD, with an AHI of 5-15 events/hour (mean 9.9+/-3.4 events/hour) and 18 patients had moderate to severe SRBD (mean 26.6+/-11.3 events/hour). Mainly, obstructive apneas were found. Subgroups were not different regarding EuroSCORE (European System for Cardiac Operative Risk Evaluation) or aortic valve area. Also, no correlations were found between AHI and the additive or logistic EuroSCORE or aortic valve area. Significant correlations were found for AHI and N-terminal of the prohormone brain natriuretic peptide (r=0.53; P=0.003) and for AHI and glomerular filtration rate (r = -0.39; P=0.007). CONCLUSION: SRBD is common in elderly patients with symptomatic aortic valve stenosis admitted for transcatheter aortic valve replacement. Interestingly, this finding is not reflected by the currently used risk scores. Further randomized studies are needed to evaluate the clinical significance of concomitant SRBD in the management of severe aortic stenosis. PMID- 26379431 TI - Association between vitamin D receptor polymorphisms and osteoporosis in patients with COPD. AB - BACKGROUND: Patients with COPD are at an increased risk of osteoporosis. Although many studies have addressed the relationship between the vitamin D receptor (VDR) polymorphisms and bone health, this relationship has not been fully investigated in patients with COPD. In this study, we investigated the association of VDR polymorphisms with bone mineral density (BMD) and other clinical parameters in patients with COPD. PATIENTS AND METHODS: In total, 200 patients with COPD were included in this study. The VDR polymorphisms rs1544410 (A/G-BsmI), rs7975232 (A/C-ApaI), rs731236 (C/T-TaqI), and rs10735810 (C/T-FokI) were determined by Sanger sequencing using blood DNA samples. BMD of the lumbar vertebra and the femoral neck was measured by dual-energy X-ray absorptiometry. Other clinical parameters were also evaluated. Haplotype and multivariate analyses were also performed. RESULTS: Sex, body mass index, steroid use, percentage of forced expiratory volume in 1 second (FEV1), alkaline phosphatase, and 25-hydroxyvitamin D significantly influenced the risk of osteoporosis. Patients with osteoporosis were more likely to carry the rs7975232 C allele compared to normal patients with BMD. Haplotypes GCT and GAT were related to osteoporosis. Patients without the haplotype GAT allele showed a significantly lower T-score at the femoral neck and an increased risk of osteoporosis (odds ratio [OR]= 2.78, 95% confidence interval [CI]= 1.20-6.48, P=0.018) compared with carriers in the dominant model. CONCLUSION: Genetic variations in VDR are significantly associated with osteoporosis among patients with COPD. Further studies are required to confirm the role of the VDR polymorphisms in osteoporosis among patients with COPD. PMID- 26379432 TI - Lung function decline rates according to GOLD group in patients with chronic obstructive pulmonary disease. AB - BACKGROUND: Since the Global Initiative for Chronic Obstructive Lung Disease (GOLD) groups A-D were introduced, the lung function changes according to group have been evaluated rarely. OBJECTIVE: We investigated the rate of decline in annual lung function in patients categorized according to the 2014 GOLD guidelines. METHODS: Patients with COPD included in the Korean Obstructive Lung Disease (KOLD) prospective study, who underwent yearly postbronchodilator spirometry at least three times, were included. The main outcome was the annual decline in postbronchodilator forced expiratory volume in 1 second (FEV1), which was analyzed by random-slope and random-intercept mixed linear regression. RESULTS: A total 175 participants were included. No significant postbronchodilator FEV1 decline was observed between the groups (-34.4+/-7.9 [group A]; -26.2+/-9.4 [group B]; -22.7+/-16.0 [group C]; and -24.0+/-8.7 mL/year [group D]) (P=0.79). The group with less symptoms (-32.3+/-7.2 vs -25.0+/-6.5 mL/year) (P=0.44) and the low risk group (-31.0+/-6.1 vs -23.6+/-7.7 mL/year) (P=0.44) at baseline showed a more rapid decline in the postbronchodilator FEV1, but the trends were not statistically significant. However, GOLD stages classified by FEV1 were significantly related to the annual lung function decline. CONCLUSION: There was no significant difference in lung function decline rates according to the GOLD groups. Prior classification using postbronchodilator FEV1 predicts decline in lung function better than does the new classification. PMID- 26379433 TI - The relationship between cough-specific quality of life and abdominal muscle endurance, fatigue, and depression in patients with COPD. AB - BACKGROUND: Cough is a prevalent symptom that impacts quality of life in COPD. The aim of this study was to assess the relationship between cough-specific quality of life, abdominal muscle endurance, fatigue, and depression in stable patients with COPD. METHODS: Twenty-eight patients with COPD (mean age 60.6+/-8.7 years) referred for pulmonary rehabilitation participated in this cross-sectional study. Sit-ups test was used for assessing abdominal muscle endurance. Leicester Cough Questionnaire (LCQ) was used to evaluate symptom-specific quality of life. Fatigue perception was evaluated with Fatigue Impact Scale (FIS). Beck Depression Inventory (BDI) was used for assessing depression level. RESULTS: The LCQ total score was significantly associated with number of sit-ups; BDI score; FIS total; physical, cognitive, and psychosocial scores (P<0.05). Scores of the LCQ physical, social, and psychological domains were also significantly related with number of sit-ups, FIS total score, and BDI score (P<0.05). FIS total score and number of sit-ups explained 58% of the variance in LCQ total score (r=0.76, r (2)=0.577, F(2-20)=12.296, P<0.001). CONCLUSION: Chronic cough may adversely affect performance in daily life due to its negative effect on fatigue and decrease abdominal muscle endurance in patients with COPD. Decreased cough related quality of life is related with increased level of depression in COPD patients. Effects of increased abdominal muscle endurance and decreased fatigue in COPD patients with chronic cough need further investigation. PMID- 26379434 TI - Influence of cationic lipid concentration on properties of lipid-polymer hybrid nanospheres for gene delivery. AB - Nanoparticles have been widely used for nonviral gene delivery. Recently, cationic hybrid nanoparticles consisting of two different materials were suggested as a promising delivery vehicle. In this study, nanospheres with a poly(D,L-lactic-co-glycolic acid) (PLGA) core and cationic lipid shell were prepared, and the effect of cationic lipid concentrations on the properties of lipid polymer hybrid nanocarriers investigated. Lipid-polymer hybrid nanospheres (LPHNSs) were fabricated by the emulsion-solvent evaporation method using different concentrations of cationic lipids and characterized for size, surface charge, stability, plasmid DNA-binding capacity, cytotoxicity, and transfection efficiency. All LPHNSs had narrow size distribution with positive surface charges (zeta-potential 52-60 mV), and showed excellent plasmid DNA-binding capacity. In vitro cytotoxicity measurements with HEK293T, HeLa, HaCaT, and HepG2 cells also showed that LPHNSs exhibited less cytotoxicity than conventional transfection agents, such as Lipofectamine and polyethyleneimine-PLGA. As cationic lipid concentrations increased, the particle size of LPHNSs decreased while their zeta potential increased. In addition, the in vitro transfection efficiency of LPHNSs increased as lipid concentration increased. PMID- 26379436 TI - Free radical scavenging in vitro and biological activity of diphenyl diselenide loaded nanocapsules: DPDS-NCS antioxidant and toxicological effects. AB - Selenium compounds, such as diphenyl diselenide (DPDS), have been shown to exhibit biological activity, including antioxidant effects. However, the use of DPDS in pharmacology is limited due to in vivo pro-oxidative effects. In addition, studies have shown that DPDS-loaded nanocapsules (DPDS-NCS) have greater bioavailability than free DPDS in mice. Accordingly, the aim of this study was to investigate the antioxidant properties of DPDS-NCS in vitro and biological activity in mice. Our in vitro results suggested that DPDS-NCS significantly reduced the production of reactive oxygen species and Fe(II) induced lipid peroxidation (LPO) in brain. The administration of DPDS-NCS did not result in death or change the levels of endogenous reduced or oxidized glutathione after 72 hours of exposure. Moreover, ex vivo assays demonstrated that DPDS-NCS significantly decreased the LPO and reactive oxygen species levels in the brain. In addition, the highest dose of DPDS-NCS significantly reduced Fe(II)- and sodium nitroprusside-induced LPO in the brain and Fe(II)-induced LPO in the liver. Also, delta-aminolevulinate acid dehydratase within the brain was inhibited only in the highest dose of DPDS-NCS. In conclusion, our data demonstrated that DPDS-NCS exhibited low toxicity in mice and have significant antioxidant characteristics, indicating that nanoencapsulation is a safer method of DPDS administration. PMID- 26379435 TI - Different patterns of nuclear and mitochondrial penetration by the G3 PAMAM dendrimer and its biotin-pyridoxal bioconjugate BC-PAMAM in normal and cancer cells in vitro. AB - The intracellular localization and colocalization of a fluorescently labeled G3 amine-terminated cationic polyamidoamine (PAMAM) dendrimer and its biotin pyridoxal (BC-PAMAM) bioconjugate were investigated in a concentration-dependent manner in normal human fibroblast (BJ) and squamous epithelial carcinoma (SCC-15) cell lines. After 24 hours treatment, both cell lines revealed different patterns of intracellular dendrimer accumulation depending on their cytotoxic effects. Cancer cells exhibited much higher (20-fold) tolerance for native PAMAM treatment than fibroblasts, whereas BC-PAMAM was significantly toxic only for fibroblasts at 50 uM concentration. Fibroblasts accumulated the native and bioconjugated dendrimers in a concentration-dependent manner at nontoxic range of concentration, with significantly lower bioconjugate loading. After reaching the cytotoxicity level, fluorescein isothiocyanate-PAMAM accumulation remains at high, comparable level. In cancer cells, native PAMAM loading at higher, but not cytotoxic concentrations, was kept at constant level with a sharp increase at toxic concentration. Mander's coefficient calculated for fibroblasts and cancer cells confirmed more efficient native PAMAM penetration as compared to BC-PAMAM. Significant differences in nuclear dendrimer penetration were observed for both cell lines. In cancer cells, PAMAM signals amounted to ~25%-35% of the total nuclei area at all investigated concentrations, with lower level (15%-25%) observed for BC-PAMAM. In fibroblasts, the dendrimer nuclear signal amounted to 15% at nontoxic and up to 70% at toxic concentrations, whereas BC-PAMAM remained at a lower concentration-dependent level (0.3%-20%). Mitochondrial localization of PAMAM and BC-PAMAM revealed similar patterns in both cell lines, depending on the extracellular dendrimer concentration, and presented significantly lower signals from BC-PAMAM, which correlated well with the cytotoxicity. PMID- 26379437 TI - Platelet activating factors are associated with depressive symptoms in coronary artery disease patients: a hypothesis-generating study. AB - INTRODUCTION: Depression is a frequent complication of coronary artery disease (CAD) with an unknown etiology. Platelet activating factor (PAF) lipids, which are associated with CAD, have recently been linked with novel proposed etiopathological mechanisms for depression such as inflammation, oxidative/nitrosative stress, and vascular endothelial dysfunction. METHODS AND RESULTS: This hypothesis-generating study investigated the relationships between various PAF species and depressive symptoms in 26 CAD patients (age: 60.6+/-9.2 years, 69% male, mean Hamilton Depression Rating Scale [HAM-D] score: 11.8+/-5.2, HAM-D range: 3-20). Plasma PAF analyses were performed using high performance liquid chromatography electrospray ionization mass spectrometry in precursor ion scan. Significant associations between depressive symptom severity (HAM-D score) and a greater plasma abundance of the PAFs phosphocholine (PC) PC(O-12:0/2:0) (r=0.49, P=0.01), PC(O-14:1/2:0) (r=0.43, P=0.03), PC(O-17:3/2:0) (r=0.44, P=0.04), and PC(O-18:3/2:0) (r=0.50, P=0.01) were observed. Associations between those PAFs and HAM-D score persisted after adjusting for age and sex. CONCLUSION: These preliminary findings support the exploration of the PAF lipidome for depressive symptom biomarkers in CAD patients. Patients were recruited as part of the following clinical trial: NCT00981383. PMID- 26379438 TI - Real-world analysis of the Celgene Global Drug Safety database: early discontinuation of lenalidomide in patients with myelodysplastic syndromes due to non-serious rash. AB - BACKGROUND: Lenalidomide is approved for treating transfusion-dependent anemia due to lower-risk del(5q) myelodysplastic syndromes (MDS). In clinical trials, rash was common, although severe rash was infrequent. To examine rash in patients with MDS treated with lenalidomide in the real world, the Celgene Global Drug Safety database was analyzed and compared with clinical trials. MATERIALS AND METHODS: Adverse event reports in the post-marketing setting and in the MDS 003/004 clinical trials were analyzed by action taken with lenalidomide, seriousness/grade, time to onset, and treatment duration. RESULTS: Globally, 16,942 reports representing 36,793 adverse events from the post-marketing setting were submitted to the Global Drug Safety database between December 27, 2005 and June 13, 2013. Most rash adverse events were non-serious (Global Drug Safety database, 91%) or grade 1/2 (MDS-003/004 trials, 87%-93%). Unexpectedly, rash, occurring at a median of 9 days after treatment initiation, was the leading cause of permanent discontinuation of lenalidomide. Seventy-two percent of non-serious rash adverse events led to early permanent discontinuation within two cycles, while in the MDS-003/004 pivotal clinical trials, only 2%-3% of rash adverse events led to permanent discontinuation. CONCLUSION: Non-serious rash was the most common reason for permanent discontinuation of lenalidomide in real-world settings. Managing lenalidomide-related rash using published recommendations might improve treatment duration and optimize patient outcomes. PMID- 26379439 TI - A case series of pregnancy- and lactation-associated osteoporosis and a review of the literature. AB - The syndrome of pregnancy- and lactation-associated osteoporosis is a rare disorder whose precise etiology and treatment are largely unknown. We herein report two such cases occurring in the early postpartum period that led to multiple fragility compression fractures. Combination therapy of vitamin D and vitamin K enabled a marked gradual increase in bone mineral density. PMID- 26379440 TI - The hepatitis B virus reactivation after transarterial chemoembolization in Chinese hepatocellular carcinoma patients with low serum hepatitis B virus DNA level. AB - OBJECTIVE: To investigate the reactivation of the hepatitis B virus (HBV) following transarterial chemoembolization (TACE) in Chinese hepatocellular carcinoma (HCC) patients with low serum HBV DNA level, and to analyze the factors related to HBV reactivation in HCC patients with low serum HBV DNA level. METHODS: From November 2011 to January 2014, 109 patients newly diagnosed with HCC with an HBV DNA level less than 2,000 IU/mL were enrolled in the study. These patients underwent at least two TACE procedures and were followed-up for at least 3 months to assess the reactivation of HBV DNA. Ten variables were compared in patients with and without HBV reactivation to evaluate the factors related to HBV reactivation in HCC patients with low serum HBV DNA level. RESULTS: Of 109 HCC patients with low level HBV DNA, nine patients were HBeAg-positive, the other 100 patients were HBeAg-negative. Twenty-three of 109 (21.1%) patients developed HBV reactivation after TACE. Of nine HBeAg-positive patients, 55.6% (5/9) developed HBV reactivation, while in 100 HBeAg-negative patients, the rate of HBV reactivation was 18% (18/100) (P=0.019). Of ten variables of patients with low level HBV DNA, the levels of AFP and HBeAg status were found to be significantly correlated with HBV reactivation. Nevertheless, on binary logistic regression analysis, only HBeAg-positive status was the independent predictor of HBV reactivation in HCC patients with low serum HBV DNA level (odds ratio, 7.41; P=0.013). CONCLUSION: HCC patients with low serum HBV DNA level still remain associated with risk of viral reactivation after TACE, and HBeAg-positive HCC patients have a higher risk than patients with HBeAg-negative status. PMID- 26379441 TI - No associations between aromatase gene polymorphisms and breast cancer risk in Saudi patients. AB - BACKGROUND: Cytochrome P450 (CYP)19A1 encodes aromatase, the enzyme responsible for the conversion of androgens to estrogens, and may play a role in variation in outcomes among women with breast cancer. The aim of this study was to analyze the genetic association of rs4646 (A > C) and rs700518 (Val > Val) in the CYP19A1 gene with the risk of breast cancer. METHODS: These two single nucleotide polymorphisms (SNPs) were analyzed in a primary study group of breast cancer patients and healthy control subjects. Genotypes were determined by the TaqMan SNP analysis technique. The study data were analyzed using the chi-square or t test and logistic regression analysis by Statistical Package for the Social Sciences version 16 software. RESULTS: rs4646 and rs700518 had no association with susceptibility to breast cancer. There was no significant association for either of these SNPs overall in breast cancer samples when compared with healthy control samples. Our data do not support a relationship between the CYP19A1 rs4646 and rs700518 SNPs and risk of breast cancer. It may be that there are ethnic differences with regard to this relationship. CONCLUSION: This study demonstrated that CYP19A1 rs4646 and rs700518 SNPs may not be involved in the etiology of breast cancer in the Saudi population. Confirmation of our findings in larger populations of other ethnicities could provide evidence for the role of the CYP19A1 gene in breast carcinomas. PMID- 26379442 TI - C-reactive protein is associated with low-density lipoprotein cholesterol and obesity in type 2 diabetic Sudanese. AB - BACKGROUND: Type 2 diabetes is emerging in Sudan and is associated with obesity. Deregulated lipid metabolism and inflammatory states are suggested risk factors for cardiovascular disease, which is a leading cause of diabetic death. This study aimed to investigate C-reactive protein (CRP) levels and the lipid profile in type 2 diabetic adult Sudanese compared with nondiabetics, and to test their associations with other characteristics. METHODS: A cross-sectional study including 70 diabetics and 40 nondiabetics was conducted. Anthropometric measurements were assessed, and demographic and medical data were obtained using a structured questionnaire. Blood specimens were collected and biochemical parameters were analyzed applying standard methods. RESULTS: CRP and triglycerides were significantly higher in the diabetic group (P<0.001 and P=0.01, respectively). Differences in total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were not statistically significant between the diabetic and nondiabetic groups. In the diabetic group, correlation analysis revealed that the CRP level had a significant positive correlation with LDL-C (r=0.255, P=0.034) and body mass index (r=0.29, P=0.016). Body mass index showed a significant positive correlation with triglycerides (r=0.386, P=0.001). Within the lipid parameters, a number of significant correlations were observed. Elevated levels of CRP, LDL-C, and triglycerides were markedly more prevalent in the diabetic group of patients. Diabetics showed significantly higher CRP levels compared with nondiabetics (odds ratio 5.56, P=0.001). CONCLUSION: The high prevalence of obesity among diabetics, together with elevated levels of triglycerides and CRP, suggest coexistence of dyslipidemia and inflammation in diabetes. Our findings emphasize that diabetics were 5.6 times more likely to have high CRP levels than nondiabetics; as CRP is a predictor of cardiovascular disease risk, it can be recognized that diabetics are at more risk of cardiovascular disease than nondiabetics. Considering evaluation of CRP together with the lipid profile in prediction of cardiovascular disease risk in Sudanese diabetics should be further tested in large-scale studies. PMID- 26379443 TI - Practical and clinical considerations in assessing patients with atrial fibrillation for switching to non-vitamin K antagonist oral anticoagulants in primary care. AB - Atrial fibrillation (AF) is an important risk factor for thromboembolic events, and anticoagulation therapy can reduce this risk. Vitamin K antagonists (VKAs), such as warfarin, have been used for decades in patients with AF for stroke prevention. Currently, non-VKA oral anticoagulants (NOACs) are approved and available for non-valvular AF patients who are at increased risk of stroke. These agents are safe and effective and have important advantages over VKAs, such as significant reduction in intracranial hemorrhage and no need for routine laboratory monitoring. Thus, should all VKA-treated patients be switched to a NOAC? The aims of this article are: 1) to review the advantages of NOACs over VKAs; 2) to identify the group of patients who most benefit from receiving a NOAC and, therefore, are higher priority to be switched from VKAs; and 3) to provide clinical and practical guidance on how to switch patients safely from VKAs to NOACs. PMID- 26379444 TI - The Effect of Subchronic Dosing of Ciproxifan and Clobenpropit on Dopamine and Histamine Levels in Rats. AB - The present study was designed to investigate the effect of once daily for 7-day (subchronic treatment) dosing of histamine H3 receptor antagonists, ciproxifan (CPX) (3 mg/kg, i.p.), and clobenpropit (CBP) (15 mg/kg, i.p), including clozapine (CLZ) (3.0 mg/kg, i.p.) and chlorpromazine (CPZ) (3.0 mg/kg, i.p.), the atypical and typical antipsychotic, respectively, on MK-801(0.2 mg/kg, i.p.) induced locomotor activity, and dopamine and histamine levels in rats. Dopamine and histamine levels were measured in striatum and hypothalamus, respectively, of rat brain. Atypical and typical antipsychotics were used to serve as clinically relevant reference agents to compare the effects of the H3 receptor antagonists. MK-801-induced increase of horizontal activity was reduced with CPX and CBP. The attenuation of MK-801-induced locomotor hyperactivity produced by CPX and CBP was comparable to CLZ and CPZ. MK-801 raised dopamine levels in the striatum, which was reduced in rats pretreated with CPX and CBP. CPZ also lowered striatal dopamine levels, though the decrease was less robust compared to CLZ, CPX and CBP. MK-801 increased histamine content although to a lesser degree. Subchronic treatment with CPX and CBP exhibited further increase in histamine levels in the hypothalamus compared to the MK-801 treatment alone. Histamine H3 receptor agonist, R-alpha methylhistamine (10 mg/kg, i.p.) counteracted the effects of CPX and CBP. In conclusion, the subchronic dosing of CPX/CBP suggests some antipsychotic-like activities as CPX/CBP counteracts the modulatory effects of MK 801 on dopamine and histamine levels and prevents MK-801-induced hyperlocomotor behaviors. PMID- 26379445 TI - Are there efficacious treatments for treating the fatigue-sleep disturbance depression symptom cluster in breast cancer patients? A Rapid Evidence Assessment of the Literature (REAL((c))). AB - PURPOSE: While fatigue, sleep disturbance, and depression often co-occur in breast cancer patients, treatment efficacy for this symptom cluster is unknown. A systematic review was conducted to determine whether there are specific interventions (ie, medical, pharmacological, behavioral, psychological, and complementary medicine approaches) that are effective in mitigating the fatigue sleep disturbance-depression symptom cluster in breast cancer patients, using the Rapid Evidence Assessment of the Literature (REAL((c))) process. METHODS: Peer reviewed literature was searched across multiple databases; from database inception - October 2011, using keywords pre-identified to capture randomized controlled trials (RCT) relevant to the research question. Methodological bias was assessed using the Scottish Intercollegiate Guidelines Network (SIGN) 50 checklist. Confidence in the estimate of effect and assessment of safety were also evaluated across the categories of included interventions via the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) methodology. RESULTS: The initial search yielded 531 citations, of which 41 met the inclusion criteria. Of these, twelve RCTs reported on all three symptoms, and eight of these were able to be included in the GRADE analysis. The remaining 29 RCTs reported on two symptoms. Studies were of mixed quality and many were underpowered. Overall, results suggest that there is: 1) promising evidence for the effectiveness of various treatment types in mitigating sleep disturbance in breast cancer patients; 2) mixed evidence for fatigue; 3) little evidence for treating depression; and 4) no clear evidence that treatment of one symptom results in effective treatment for other symptoms. CONCLUSION: More high-quality studies are needed to determine the impact of varied treatments in mitigating the fatigue-sleep disturbance-depression symptom cluster in breast cancer patients. Furthermore, we encourage future studies to examine the psychometric and clinical validity of the hypothesized relationship between the symptoms in the fatigue sleep disturbance-depression symptom cluster. PMID- 26379446 TI - Taxanes in the elderly patient with metastatic breast cancer. AB - More than 40% of all breast cancer cases are diagnosed in patients aged >=65 years, accounting for an ever-increasing disease burden in the elderly. Historically, however, this growing population of breast cancer patients has been underrepresented in clinical trials, resulting in a paucity of data that clinicians can reference in making treatment decisions for their older patients. A consequence may be the undertreatment of elderly patients, who have the highest incidence of breast cancer. However, subgroup analyses of elderly patients in multiple early-Phase (I or II) studies and a handful of small studies with elderly-specific populations have suggested that older patients may experience similar benefit from cancer therapy as younger patients with otherwise similar baseline characteristics. Although steps should be taken to avoid undertreating older patients, a balance must be achieved to avoid overtreatment. Guidelines have been released detailing recommendations for the treatment of elderly breast cancer patients, including a discussion of various geriatric assessments that might aid physicians in selecting patients appropriate for recommended treatment options. Chemotherapy remains a key component of treatment regimens for many older patients. However, the benefit of some agents may be limited by tolerability issues. Taxanes, one of the most established classes of chemotherapy for breast cancer, are known to be highly active and efficacious and to have well characterized safety profiles. This review discusses factors that influence treatment choices for elderly patients with metastatic breast cancer, and then focuses on clinical data for taxanes in this patient population. PMID- 26379448 TI - Anterior uveitis following eyebrow epilation with alexandrite laser. AB - Ocular tissues are known to be sensitive to damage from exposure to laser emissions. This study reports the case of a female patient with acute unilateral anterior uveitis caused by alexandrite laser-assisted hair removal of the eyebrows. We report a 38-year-old female who presented with unilateral eye pain, redness, and photophobia after receiving alexandrite (755 nm) laser epilation of both eyebrows. Best corrected visual acuity was 20/20 in both eyes. Right eye examination was normal. Left eye examination showed conjunctival injection and 2+/3+ cells in the anterior chamber. Intraocular pressure and fundus examination were normal. Topical steroids and cycloplegic drops were prescribed for 3 weeks. At the end of the 3-week follow-up, best corrected visual acuity was 20/20, and intraocular pressure and fundus examination were normal in both eyes. The left eye was white, and the anterior chamber was clear. The patient continues to be monitored. In conclusion, without adequate protective eyewear, laser hair removal of the eyebrows with alexandrite laser can lead to ocular damage. PMID- 26379449 TI - Diagnostic and therapeutic considerations in idiopathic hypereosinophilia with warm autoimmune hemolytic anemia. AB - Hypereosinophilic syndrome (HES) encompasses numerous diverse conditions resulting in peripheral hypereosinophilia that cannot be explained by hypersensitivity, infection, or atopy and that is not associated with known systemic diseases with specific organ involvement. HES is often attributed to neoplastic or reactive causes, such as chronic eosinophilic leukemia, although a majority of cases remains unexplained and are considered idiopathic. Here, we review the current diagnosis and management of HES and present a unique case of profound hypereosinophilia associated with warm autoimmune hemolytic anemia requiring intensive management. This case clearly illustrates the limitations of current knowledge with respect to hypereosinophilia syndrome as well as the challenges associated with its classification and management. PMID- 26379447 TI - The network of pluripotency, epithelial-mesenchymal transition, and prognosis of breast cancer. AB - Breast cancer is the leading female cancer in terms of prevalence. Progress in molecular biology has brought forward a better understanding of its pathogenesis that has led to better prognostication and treatment. Subtypes of breast cancer have been identified at the genomic level and guide therapeutic decisions based on their biology and the expected benefit from various interventions. Despite this progress, a significant percentage of patients die from their disease and further improvements are needed. The cancer stem cell theory and the epithelial mesenchymal transition are two comparatively novel concepts that have been introduced in the area of cancer research and are actively investigated. Both processes have their physiologic roots in normal development and common mediators have begun to surface. This review discusses the associations of these networks as a prognostic framework in breast cancer. PMID- 26379450 TI - Complex Coronary Interventions with the Novel MozecTM CTO Balloon: The MOZART Registry. AB - BACKGROUND: MozecTM CTO is a novel semicompliant rapid-exchange PTCA balloon catheter with specific features dedicated to treat complex coronary lesions like chronic total occlusions (CTOs). However, no data have been reported about the performance of this device in an all-comers population with complex coronary lesions. METHODS: We evaluated the safety and success rate of MozecTM CTO balloon in 41 consecutive patients with chronic stable angina and complex coronary lesions (15 severe calcified coronary stenoses, 15 bifurcation lesions with planned two-stent intervention, and 11 CTOs). Safety was assessed reporting the balloon burst rate after inflation exceeding the rated burst pressure (RBP) according to the manufacturer's reference table. Success was defined as the possibility to advance the device further the target lesion. RESULTS: The MozecTM CTO balloon showed an excellent performance with a 93.3% success in crossing tight and severely calcified lesions (14/15 pts), a 93.3% success in engaging jailed side branches after stent deployment across bifurcations (14/15 pts), and a 90.9% success in crossing CTO lesions (10/11 pts). The burst rate at RBP of the MozecTM CTO balloon was 6.7% (1/15 balloons) in the tight and severely calcified lesions, 6.7% (1/15 balloons) when dilating jailed vessels, and 9.1% (1/11 balloons) in CTOs. CONCLUSIONS: The novel MozecTM CTO balloon dilatation catheter showed promising results when employed to treat complex lesions in an all-comers population. Further studies should clarify if this kind of balloon might reduce the need of more costly devices like over-the-wire balloons and microcatheters for complex lesions treatment. PMID- 26379451 TI - Cytomegalovirus-induced Hemorrhagic Colitis in a Patient with Chronic Myeloid Leukemia (Chronic Phase) on Dasatinib as an Upfront Therapy. AB - Dasatinib is a kinase inhibitor indicated for the treatment of newly diagnosed adults with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase and accelerated (myeloid or lymphoid blast) phase, and CML with resistance or intolerance to prior therapy including imatinib and in adults with Ph+ acute lymphoblastic leukemia1 The most common adverse reactions (>=15%) in patients with newly diagnosed chronic-phase (CP) CML include myelosuppression, fluid retention, and diarrhea, whereas in patients with resistance or intolerance to prior imatinib therapy, side effects include myelosuppression, fluid retention, diarrhea, headache, dyspnea, skin rash, fatigue, nausea, and hemorrhage. We report a 39-year-old Ethiopian female patient who received dasatinib as upfront therapy for the treatment of CP-CML who experienced chronic diarrhea for two months, which progressed to hemorrhagic colitis due to cytomegalovirus (CMV) infection of the colon. To our knowledge, this is the first case of CMV colitis in a patient receiving dasatinib as upfront therapy. PMID- 26379452 TI - Knowledge and Attitude of Patients, and Practice of the Arrest of Breast Cancer in Outpatient Consultations in Mastology at the General Hospital of Huambo, Angola. AB - This work aims to understand the knowledge and perceptions of women aged over 40 years with breast cancer seen in mastology outpatients at the Maternity Hospital of Huambo, central Angola, from February to August 2010. It also examines the clinical practice of prevention and detection of breast cancer. The research consisted of a collection of descriptive, cross-sectional data through a questionnaire. Statistical analysis of the data was performed using Epi Info, version 6.04b. In our sample, half of the women were single, all had history of breast cancer in the family, and most had heard of breast self-examination, with the primary source of information being the mass media. Almost all women reported that it was important to perform self-examination and that they were aware of the seriousness of breast cancer, and although most of them had not been taught how to do breast self-examination, almost all knew the basics of how to do it. Some 17.6% had heard of mammography, but none had ever had a mammogram. PMID- 26379453 TI - Nurse educators' perceptions of critical thinking in developing countries: Ghana as a case study. AB - The ability to critically evaluate information for the purpose of rendering health care is a prerequisite for modern nurses in a complex and ever-changing health care environment. The nurse educators' perceptions influence the utilization of critical thinking strategies in the classroom. The purpose of this study was to assess nursing faculty's perceptions of critical thinking. Using a questionnaire 106 nurse educators from two types of nursing educational program self-reported their perceptions. Data were collected from November 2013 to March 2014. Results were presented using frequencies, percentages, and t-test. The findings revealed that majority (95.3%) of nurse educators could not provide definitions that captured both affective and cognitive aspects of critical thinking. However, the majority of nurse educators had positive perceptions of critical thinking. Nurse educators in universities had more positive perceptions of critical thinking than those in the nurses' training colleges (P=0.007). The results suggested that the current nursing programs are not preparing nurses with the necessary critical thinking skills for the complex health care environment. Professional development programs in critical thinking should be instituted for nurse educators to assist them in developing appropriate teaching strategies to foster students' acquisition of critical thinking skills. PMID- 26379455 TI - A new species of Harpactea Bristowe, 1939 from Turkey (Araneae: Dysderidae). AB - A new species of Harpactea Bristowe, 1939, H. alanyana sp. n. is described from southern Turkey. The new species appears closely related to H. osellai Brignoli, 1978. Detailed description and illustrations of the new and related species are provided. The relationships of the two species are discussed. PMID- 26379454 TI - The pharmacology of neurokinin receptors in addiction: prospects for therapy. AB - Addiction is a chronic disorder in which consumption of a substance or a habitual behavior becomes compulsive and often recurrent, despite adverse consequences. Substance p (SP) is an undecapeptide and was the first neuropeptide of the neurokinin family to be discovered. The subsequent decades of research after its discovery implicated SP and its neurokinin relatives as neurotransmitters involved in the modulation of the reward pathway. Here, we review the neurokinin literature, giving a brief historical perspective of neurokinin pharmacology, localization in various brain regions involved in addictive behaviors, and the functional aspects of neurokinin pharmacology in relation to reward in preclinical models of addiction that have shaped the rational drug design of neurokinin antagonists that could translate into human research. Finally, we will cover the clinical investigations using neurokinin antagonists and discuss their potential as a therapy for drug abuse. PMID- 26379456 TI - Three new species of Trigonospila Pokorny (Diptera: Tachinidae), from Area de Conservacion Guanacaste, northwestern Costa Rica, with a key for their identification. AB - We describe three new species of Trigonospila Pokorny (Tachinidae: Blondeliini) from Area de Conservacion Guanacaste (ACG), northwestern Costa Rica. All were reared from -various species of ACG caterpillars during an ongoing inventory of caterpillars, their food plants and their parasitoids in dry forest, rain forest and cloud forest. By coupling morphology, photographic documentation, life history and molecular data, we provide a clear and concise description of each species. All species published as new, are known to be previously undescribed as a result of careful study of the genus by DMW. This study builds on the current knowledge of the genus by adding three new species to the current 7 described in the New World. Trigonospila edwinbermudezi sp. n., Trigonospila uniformis sp. n., and Trigonospila josemariamoragai sp. n. are all authored and described as new by Fleming and Wood, with a key to their identification. The authors also offer a new record and description of the previously unknown male of Trigonospila panamensis (Townsend), reared from ACG caterpillars. PMID- 26379457 TI - Morpho-physiolological and qualitative traits of a bread wheat collection spanning a century of breeding in Italy. AB - Evaluation and characterization are crucial steps in the exploitation of germplasm collections. The Sant'Angelo Lodigiano unit of the Consiglio per la ricerca in agricoltura e l'analisi dell'economia agraria (CREA) maintains a broad collection of Triticum spp, including more than 4000 genotypes of T. aestivum. Such collection represents a wide source of genetic variability for many agronomic and qualitative traits, extremely useful in modern breeding programs. The collection size, however, makes very difficult its management as a whole. A reduced subset, representing the process of wheat breeding in Italy during the last hundred years, was hence identified for an in-depth characterization. The lines were cropped in two locations over two growing seasons, and analyzed using 16 morpho-agronomic and qualitative descriptors. Most of the analysed characters showed a broad variation throughout the collection, allowing to follow the plant ideotype changes across the breeding progress in Italy during the 20th century. PMID- 26379458 TI - Three new species of Ametadoria Townsend (Diptera: Tachinidae) from Area de Conservacion Guanacaste, Costa Rica. AB - We describe three new species in the genus Ametadoria Townsend from Area de Conservacion Guanacaste (ACG), Costa Rica. All three were reared from wild-caught Zygaenidae and Lacturidae caterpillars. We provide a concise description of each species using morphology, life history and molecular data, with photographic documentation. The new species are authored and described by Fleming and Wood: Ametadoria karolramosae sp. nov., Ametadoria leticiamartinezae sp. nov., and Ametadoria mauriciogurdiani sp. nov. The following are proposed by Wood as new synonyms of Ametadoria Townsend: Adidyma Townsend syn. nov., and Abolodoria Townsend syn. nov. The following new combinations occur as a result of these new synonymies: Ametadoria abdominalis (Townsend) comb. nov., Ametadoria austrina (Coquillett) comb. nov., Ametadoria humilis (Wulp) comb. nov., Ametadoria misella (Wulp) comb. nov. Ametadoria adversa (Townsend) is proposed as a junior synonym of Ametadoria unispinosa Townsend, syn. nov. PMID- 26379459 TI - New data on the rare Afrotropical scarab beetles Orphnus drumonti Frolov and Delopleurus naviauxi Frolov et Cambefort (Coleoptera, Scarabaeidae, Orphninae and Scarabaeinae). AB - BACKGROUND: The scarab beetle genera Orphnus Macleay and Delopleurus Boheman are most speciose in the Afrotropical region. However, a number of species are only known from type specimens, sometimes only from one sex. NEW INFORMATION: New locality records of Orphnus drumonti Frolov (Orphninae) and Delopleurus naviauxi Frolov et Cambefort (Scarabaeinae) are given. The previously unknown female of the former and male of the latter species are described. PMID- 26379460 TI - A new species and new records of Molophilus Curtis, 1833 (Diptera: Limoniidae) from the Western Palaearctic Region. AB - BACKGROUND: Molophilus Curtis, 1833 is the most species-rich Limoniidae genus with a total number of 1006 species and subspecies, from which 97 are recorded in the Western-Palaearctic region so far. However new species are still expected from less investigated regions, like the Balkans or the Eastern Europe. NEW INFORMATION: In the present article, we desrcibe a new limonid crane fly species, Molophilus balcanicus Kolcsar sp. n. from the Central Balkan area (Bulgaria). This new taxa is closely related to M. serpentiger Edwards, 1938 and M. variispinus Stary, 1971 based on the external male genital structures, but differs from its siblings mostly in the structure of the inner and outer gonostylus. Additionally, a number of species are reported for the first time from various European countries, like M. variispinus Stary, 1971 and M. occultus de Meijere, 1918 from Romania; M. crassipygus de Meijere 1918, M. obsoletus Lackschewitz, 1940 and M. medius de Meijere, 1918 from Greece; M. flavus Goetghebuer, 1920 from Andorra; M. cinereifrons de Meijere, 1920 from Bulgaria and M. corniger Meijere, 1920 from Spain. PMID- 26379461 TI - A general methodology for collecting and preserving xystodesmid and other large millipedes for biodiversity research. AB - BACKGROUND: With an estimated 80% of species remaining undescribed (but see Brewer et al. 2012), millipede taxonomy offers the opportunity to discover new species and explore biodiversity. The lack of basic alpha taxonomic information regarding millipedes belies their significant ecological role and potential as premier models in ecological and evolutionary studies. The group possesses many fascinating biological properties (e.g., bioluminescence, mimicry, and complex chemical secretions) that have been the focus of several recent studies and are emerging avenues of future investigation. NEW INFORMATION: Here we summarize a methodology for large-bodied millipede collection, curation, and preservation for genetic analyses with the hope that sharing these techniques will stimulate interest in these charismatic detritivores. PMID- 26379462 TI - Range extension of Myotis midastactus (Chiroptera, Vespertilionidae) to Paraguay. AB - BACKGROUND: Myotis midastactus Moratelli and Wilson, 2014 (Vespertilionidae, Myotinae) was described from the Myotis simus Thomas, 1901 complex based on collections from the Bolivian Savannah. NEW INFORMATION: Four vouchers previously assigned to M. simus from the Alto Chaco in Paraguay (West of the Paraguay River) are reassigned here to M. midastactus. These specimens extend the geographic distribution of M. midastactus 1200 km southward, and constitute the first evidence of the species in the country. Based on other material from the Brazilian Pantanal and Cerrado, Central Paraguay and north-eastern Argentina, we also discuss the identity of simus-like populations south of the Amazon Basin. The status of these populations is still unclear, but the little evidence we have at hand indicates that these populations may represent another taxon-M. guaycuru Proenca, 1943; whereas M. simus seems to be restricted to the Amazon basin. This hypothesis is still very speculative and requires further investigation. With the assignment of material from Alto Chaco to M. midastactus, seven species of Myotis are confirmed for Paraguay: M. albescens, M. lavali, M. levis, M. midastactus, M. nigricans, M. riparius, and M. ruber. PMID- 26379463 TI - Fauna Europaea: Annelida - Terrestrial Oligochaeta (Enchytraeidae and Megadrili), Aphanoneura and Polychaeta. AB - Fauna Europaea provides a public web-service with an index of scientific names (including important synonyms) of all living European land and freshwater animals, their geographical distribution at country level (up to the Urals, excluding the Caucasus region), and some additional information. The Fauna Europaea project covers about 230,000 taxonomic names, including 130,000 accepted species and 14,000 accepted subspecies, which is much more than the originally projected number of 100,000 species. This represents a huge effort by more than 400 contributing specialists throughout Europe and is a unique (standard) reference suitable for many users in science, government, industry, nature conservation and education. This paper provides updated information on the taxonomic composition and distribution of the Annelida - terrestrial Oligochaeta (Megadrili and Enchytraeidae), Aphanoneura and Polychaeta, recorded in Europe. Data on 18 families, 11 autochthonous and 7 allochthonous, represented in our continent by a total of 800 species, are reviewed, beginning from their distinctness, phylogenetic status, diversity and global distribution, and following with major recent developments in taxonomic and faunistic research in Europe. A rich list of relevant references is appended. The Fauna Europaea Annelida - terrestrial Oligochaeta data-set, as completed in 2004, will be updated accordingly. PMID- 26379464 TI - Description of Aegialoalaimus bratteni sp. n. from Skagerrak and a review of the genus (Aegialoalaimidae, Nematoda incertae sedis). AB - BACKGROUND: The genus Aegialoalaimus de Man, 1907 includes 12 nominal species, of which three species are considered valid, two species were transferred to other genera and seven species have uncertain taxonomic status. NEW INFORMATION: New species, Aegialoalaimus bratteni sp. n. was found in Skagerrak off the west coast of Sweden. It is particularly characterized by the 1.5-1.8 mm long body, short papilliform cephalic sensilla, excretory pore opening just posterior to nerve ring level, spicules that are straight in shape, supplements and gubernaculum absent, separating it from other valid species of the genus. It can be further differentiated from Aegialoalaimus elegans in having longer body (1.5-1.8 mm in A. bratteni sp. n. vs 0.8-1.3 mm in A. elegans), shape and size of spicules (straight and 22-29 um long in A. bratteni sp. n. vs arcuate and 34 um long in A. elegans), absence of precloacal supplements (vs seven-eight in A. elegans), absence of gubernaculum (vs present in A. elegans); from A. setosa in having shorter tail (c'=2.6-3.1 in A. bratteni sp. n. vs c'=4.2 in A. setosa), shorter cephalic sensilla (0.5-1.0 um in A. bratteni sp. n. vs 9 um in A. setosa), shape and size of spicules (straight and 22-29 um long in A. bratteni sp. n. vs arcuate and 40-45 um long in A. setosa), absence of precloacal supplements (vs eight in A. setosa), absence of gubernaculum (vs present in A. setosa); from A. leptosoma in having longer body (1.5-1.8 mm in A. bratteni sp. n. vs 0.5-0.7 mm in A. leptosoma) and other measurements, shape of spicules (straight in A. bratteni sp. n. vs arcuate in A. leptosoma), absence of precloacal supplements (vs three-five in A. leptosoma), absence of gubernaculum (vs present in A. leptosoma). Type specimens of Aegialoalaimus cylindricauda Allgen, 1933 and A. paratenuicaudatus Allgen, 1959 are redescribed and taxonomic status of these two species is re evaluated. A taxonomic review, tabular compendium and identification key for species of the genus Aegialoalaimus are also given. PMID- 26379465 TI - Global Cicada Sound Collection I: Recordings from South Africa and Malawi by B. W. Price & M. H. Villet and harvesting of BioAcoustica data by GBIF. AB - BACKGROUND: Sound collections for singing insects provide important repositories that underpin existing research (e.g. Price et al. 2007 at http://bio.acousti.ca/node/11801; Price et al. 2010) and make bioacoustic collections available for future work, including insect communication (Ordish 1992), systematics (e.g. David et al. 2003), and automated identification (Bennett et al. 2015). The BioAcoustica platform (Baker et al. 2015) is both a repository and analysis platform for bioacoustic collections: allowing collections to be available in perpetuity, and also facilitating complex analyses using the BioVeL cloud infrastructure (Vicario et al. 2011). The Global Cicada Sound Collection is a project to make recordings of the world's cicadas (Hemiptera: Cicadidae) available using open licences to maximise their potential for study and reuse. This first component of the Global Cicada Sound Collection comprises recordings made between 2006 and 2008 of Cicadidae in South Africa and Malawi. NEW INFORMATION: This collection of sounds includes 219 recordings of 133 voucher specimens, comprising 42 taxa (25 identified to species, all identified to genus) from South Africa and Malawi. The recordings have been used to underpin work on the species limits of cicadas in southern Africa, including Price et al. (2007) and Price et al. (2010). The specimens are deposited in the Albany Museum, Grahamstown, South Africa (AMGS). The harvesting of acoustic data as occurrence records by GBIF has been implemented by the Scratchpads Team at the Natural History Museum, London. This link increases the value of individual recordings and the BioAcoustica platform within the global infrastructure of biodiversity informatics by making specimen/occurence records from BioAcoustica available to a wider audience, and allowing their integration with other occurence datasets that also contribute to GBIF. PMID- 26379466 TI - New records of Orussus minutus Middlekauff, 1983 (Hymenoptera: Orussidae) represent a significant western range expansion. AB - BACKGROUND: Orussus minutus is an uncommonly collected parasitoid sawfly known from the eastern United States. NEW INFORMATION: We report specimens Orussus minutus Middlekauff, 1983, from Arkansas, Iowa, Minnesota, and Manitoba, which represent new state and province records and significantly expand the known range of the species west from previous records; provide collection information for unpublished specimens housed in the United States National Museum collection, which includes new state records for West Virginia and Michigan; and report two specimens housed in the Biological Museum at Lund University that represent new state records for Connecticut. PMID- 26379467 TI - Fauna Europaea: Gastrotricha. AB - Fauna Europaea provides a public web-service with an index of scientific names (including important synonyms) of all living European land and freshwater animals, their geographical distribution at country level (up to the Urals, excluding the Caucasus region), and some additional information. The Fauna Europaea project covers about 230,000 taxonomic names, including 130,000 accepted species and 14,000 accepted subspecies, which is much more than the originally projected number of 100,000 species. This represents a huge effort by more than 400 contributing specialists throughout Europe and is a unique (standard) reference suitable for many users in science, government, industry, nature conservation and education. Gastrotricha are a meiobenthic phylum composed of 813 species known so far (2 orders, 17 families) of free-living microinvertebrates commonly present and actively moving on and into sediments of aquatic ecosystems, 339 of which live in fresh and brackish waters. The Fauna Europaea database includes 214 species of Chaetonotida (4 families) plus a single species of Macrodasyida incertae sedis. This paper deals with the 224 European freshwater species known so far, 9 of which, all of Chaetonotida, have been described subsequently and will be included in the next database version. Basic information on their biology and ecology are summarized, and a list of selected, main references is given. As a general conclusion the gastrotrich fauna from Europe is the best known compared with that of other continents, but shows some important gaps of knowledge in Eastern and Southern regions. PMID- 26379468 TI - New distribution records for the critically endangered frog Indirana gundia (Dubois, 1986) from Kerala part of Western Ghats, India. AB - BACKGROUND: Indirana gundia is one of the critically endangered frog species of Western Ghats, India, and known only from the type locality (Gundya in Karnataka State, India) at an elevation of 200 m Mean Sea Level. We provide data on the geographical distribution of this species using molecular tools. NEW INFORMATION: Our results expand the geographical distribution range of this species about 111 km south up to the northern part of Kerala State and recorded at an elevation ranging from 115 m to 200 m asl. PMID- 26379470 TI - One-step extraction and concentration of estrogens for an adequate monitoring of wastewater using ionic-liquid-based aqueous biphasic systems. AB - Ethinylestradiol (EE2) is a synthetic hormone that has been recognized as one of the most prominent endocrine disruptors found in the aqueous environment. Nevertheless, the low content of EE2 in wastewater makes its identification/quantification unfeasible - a major drawback for the evaluation of its persistence and environmental impact. In this context, a novel extraction/concentration method for EE2 from wastewater is proposed here based on aqueous biphasic systems composed of ionic liquids (ILs). Aqueous biphasic systems formed by several hydrophilic ILs and KNaC4H4O6 were initially screened and optimized, with extraction efficiencies of EE2 for the IL-rich phase ranging between 92 and 100%. Remarkable results were obtained with systems that allow the complete extraction of EE2 in a single-step, and without loss of EE2 or the saturation of the extractive phase. Further, the concentration factors of EE2 attainable with these systems were investigated by a suitable manipulation of the composition of the phase-forming components and the corresponding volumes of the coexisting phases. An outstanding concentration of EE2 up to 1000-fold (from ng L 1 to MUg L-1) in a single extraction and concentration step was achieved for the first time with IL-based aqueous biphasic systems. These systems are straightforwardly envisaged for the monitoring of wastewater as one-step extraction and concentration routes for a wide array of endocrine disrupting chemicals while allowing an adequate evaluation of their environmental impact. PMID- 26379471 TI - The magic of aqueous solutions of ionic liquids: ionic liquids as a powerful class of catanionic hydrotropes. AB - Hydrotropes are compounds able to enhance the solubility of hydrophobic substances in aqueous media and therefore are widely used in the formulation of drugs, cleaning and personal care products. In this work, it is shown that ionic liquids are a new class of powerful catanionic hydrotropes where both the cation and the anion synergistically contribute to increase the solubility of biomolecules in water. The effects of the ionic liquid chemical structures, their concentration and the temperature on the solubility of two model biomolecules, vanillin and gallic acid were evaluated and compared with the performance of conventional hydrotropes. The solubility of these two biomolecules was studied in the entire composition range, from pure water to pure ionic liquids, and an increase in the solubility of up to 40-fold was observed, confirming the potential of ionic liquids to act as hydrotropes. Using dynamic light scattering, NMR and molecular dynamics simulations, it was possible to infer that the enhanced solubility of the biomolecule in the IL aqueous solutions is related to the formation of ionic-liquid-biomolecules aggregates. Finally, it was demonstrated that hydrotropy induced by ionic liquids can be used to recover solutes from aqueous media by precipitation, simply by using water as an anti solvent. The results reported here have a significant impact on the understanding of the role of ionic liquid aqueous solutions in the extraction of value-added compounds from biomass as well as in the design of novel processes for their recovery from aqueous media. PMID- 26379472 TI - A synthetic standard for the analysis of carbon isotopes of carbon in silicates, and the observation of a significant water-associated matrix effect. AB - BACKGROUND: Due to the biogeochemical fractionation of isotopes, organic material can be heterogeneous at the microscale. Because this heterogentiy preserves in the rock record, the microscale measurement of carbon isotopes is an important frontier of geobiology. Such analyses via secondary ion mass spectrometry (SIMS) have been, however, held back by the lack of an appropriate homogeneous synthetic standard that can be shared between laboratories. Such a standard would need to yield a carbon signal intensity within the same instrument dynamic range as that found for typical rocks, exhibit minimal matrix effects under typical SIMS conditions, and be widely available. In this work, five possible standards were tested with repeated delta(13)C ion microprobe measurements against the PPRG #215 1 Precambrian chert that has been used as a working standard for these types of analyses by several laboratories. RESULTS: Results showed that silica powder, pressed, and bonded with Ceramacast 905 produced a useful synthetic standard. The material produced has a secondary ion carbon yield of only about 15* that of the PPRG #215-1 organic-rich chert. Finally, the material, once dried sufficiently, did not demonstrate an observable matrix effect when the carbon isotopes were measured. Another similar material (silica nanopowder, pressed, and bonded with Aremco-Bond 526N) appears to have retained its hydration after a substantial effect to dry it. The isotopes measurements of this more hydrated material showed a significant matrix effect that was diminished by intense pre-sputtering. The results indicate water can affect SIMS carbon isotopic measurements, and an intense beam reduces the effect. A hydrated standard might be useful to monitor the effect. CONCLUSIONS: A suitable artificial standard for SIMS isotopic measurements of organic material in rocks has been found, and it will allow an acute growth in both the quantity and quality of studies of ancient carbon at the microscale. Also, this work has revealed a novel water-associated matrix effect for carbon isotopes. This newly revealed matrix effect is important because it might have misled previous research. The effect could lead to increased observed heterogeneity of partially hydrated samples and/or produced systematic differences between natural targets and the standards used. PMID- 26379469 TI - Biodiversity inventories in high gear: DNA barcoding facilitates a rapid biotic survey of a temperate nature reserve. AB - BACKGROUND: Comprehensive biotic surveys, or 'all taxon biodiversity inventories' (ATBI), have traditionally been limited in scale or scope due to the complications surrounding specimen sorting and species identification. To circumvent these issues, several ATBI projects have successfully integrated DNA barcoding into their identification procedures and witnessed acceleration in their surveys and subsequent increase in project scope and scale. The Biodiversity Institute of Ontario partnered with the rare Charitable Research Reserve and delegates of the 6th International Barcode of Life Conference to complete its own rapid, barcode-assisted ATBI of an established land trust in Cambridge, Ontario, Canada. NEW INFORMATION: The existing species inventory for the rare Charitable Research Reserve was rapidly expanded by integrating a DNA barcoding workflow with two surveying strategies - a comprehensive sampling scheme over four months, followed by a one-day bioblitz involving international taxonomic experts. The two surveys resulted in 25,287 and 3,502 specimens barcoded, respectively, as well as 127 human observations. This barcoded material, all vouchered at the Biodiversity Institute of Ontario collection, covers 14 phyla, 29 classes, 117 orders, and 531 families of animals, plants, fungi, and lichens. Overall, the ATBI documented 1,102 new species records for the nature reserve, expanding the existing long-term inventory by 49%. In addition, 2,793 distinct Barcode Index Numbers (BINs) were assigned to genus or higher level taxonomy, and represent additional species that will be added once their taxonomy is resolved. For the 3,502 specimens, the collection, sequence analysis, taxonomic assignment, data release and manuscript submission by 100+ co authors all occurred in less than one week. This demonstrates the speed at which barcode-assisted inventories can be completed and the utility that barcoding provides in minimizing and guiding valuable taxonomic specialist time. The final product is more than a comprehensive biotic inventory - it is also a rich dataset of fine-scale occurrence and sequence data, all archived and cross-linked in the major biodiversity data repositories. This model of rapid generation and dissemination of essential biodiversity data could be followed to conduct regional assessments of biodiversity status and change, and potentially be employed for evaluating progress towards the Aichi Targets of the Strategic Plan for Biodiversity 2011-2020. PMID- 26379473 TI - Ecology and Distribution of Thaumarchaea in the Deep Hypolimnion of Lake Maggiore. AB - Ammonia-oxidizing Archaea (AOA) play an important role in the oxidation of ammonia in terrestrial, marine, and geothermal habitats, as confirmed by a number of studies specifically focused on those environments. Much less is known about the ecological role of AOA in freshwaters. In order to reach a high resolution at the Thaumarchaea community level, the probe MGI-535 was specifically designed for this study and applied to fluorescence in situ hybridization and catalyzed reporter deposition (CARD-FISH) analysis. We then applied it to a fine analysis of diversity and relative abundance of AOA in the deepest layers of the oligotrophic Lake Maggiore, confirming previous published results of AOA presence, but showing differences in abundance and distribution within the water column without significant seasonal trends with respect to Bacteria. Furthermore, phylogenetic analysis of AOA clone libraries from deep lake water and from a lake tributary, River Maggia, suggested the riverine origin of AOA of the deep hypolimnion of the lake. PMID- 26379474 TI - RIG-I contributes to the innate immune response after cerebral ischemia. AB - BACKGROUND: Focal cerebral ischemia induces an inflammatory response that when exacerbated contributes to deleterious outcomes. The molecular basis regarding the regulation of the innate immune response after focal cerebral ischemia remains poorly understood. METHODS: In this study we examined the expression of retinoic acid-inducible gene (RIG)-like receptor-I (RIG-I) and its involvement in regulating inflammation after ischemia in the brain of rats subjected to middle cerebral artery occlusion (MCAO). In addition, we studied the regulation of RIG-I after oxygen glucose deprivation (OGD) in astrocytes in culture. RESULTS: In this study we show that in the hippocampus of rats, RIG-I and IFN-alpha are elevated after MCAO. Consistent with these results was an increased in RIG-I and IFN-alpha after OGD in astrocytes in culture. These data are consistent with immunohistochemical analysis of hippocampal sections, indicating that in GFAP positive cells there was an increase in RIG-I after MCAO. In addition, in this study we have identified n-propyl gallate as an inhibitor of IFN-alpha signaling in astrocytes. CONCLUSION: Our findings suggest a role for RIG-I in contributing to the innate immune response after focal cerebral ischemia. PMID- 26379475 TI - Green Tea Epigallocatechin-3-Gallate Suppresses Autoimmune Arthritis Through Indoleamine-2,3-Dioxygenase Expressing Dendritic Cells and the Nuclear Factor, Erythroid 2-Like 2 Antioxidant Pathway. AB - BACKGROUND: The activity of one of the major catechins in Green Tea, the polyphenol (-)-epigallocatechin-3-gallate (EGCG), has been shown to have a variety of health benefits. Recent studies suggest that EGCG can modulate both the innate and adaptive arms of the immune system. The goal of the current studies was to examine the immunomodulatory effects and mechanisms of action of EGCG on experimental arthritis in mice. METHODS: EGCG (10 mg/kg) was administered by oral gavage after CIA induction, while control mice were administered phosphate buffered saline (PBS). Disease mechanisms were studied in both groups of mice. Phenotypes were examined using repeated measure analysis of variance (ANOVA) and data from in vitro and ex vivo experiments were analyzed for significance using the Mann-Whitney U test. RESULTS: EGCG treatment ameliorated clinical symptoms and reduced histological scores in arthritic mice. Serum type II collagen-specific immunoglobulin (Ig) IgG2a antibodies were significantly lower in EGCG-fed mice compared to PBS-treated mice. EGCG significantly suppressed T cell proliferation and relative frequencies of CD4 T cells, CD8 T cells and B cell subsets including marginal zone B cells, T1 and T2 transitional B cells, while increasing the frequency of CD4(+) Foxp3(+) regulatory T cells (Tregs) and indoleamine-2,3-dioxygenase (IDO) expression by CD11b(+) dendritic cells (DC). Splenic CD11b(+) DC from EGCG fed mice induced an increased frequency of Tregs via an IDO-dependent mechanism in in vitro cultures. Importantly, joint homogenates from EGCG-fed mice exhibited significantly increased levels of Nuclear Factor, Erythroid 2-Like 2 (Nrf-2) and Heme oxygenase-1 (HO-1) compared with PBS-fed mice. CONCLUSIONS: This is the first report of upregulation of the Nrf-2 antioxidant pathway in EGCG-mediated immunoregulation. EGCG ameliorated experimental arthritis in mice by eliciting IDO-producing DCs, increasing frequencies of T regs and inducing the activation of the Nrf-2 antioxidant pathway. It remains to be established whether EGCG is useful for the prevention and treatment of rheumatoid arthritis and other inflammatory disorders. PMID- 26379478 TI - Estimating the current mean age of mothers at the birth of their first child from household surveys. AB - BACKGROUND: Estimates of the period mean age at first birth are readily available for countries with accurate vital statistics (i.e., in much of the developed world). In contrast, in most developing countries vital statistics are lacking or incomplete and estimates of the period mean age at first birth are therefore often unavailable. The Demographic and Health Surveys (DHS) program provides a large set of demographic and health statistics for many developing countries, but not the mean age at childbearing or the mean age at first birth. METHODS: We propose two different methods for the estimation of the period mean age at first birth from information collected in DHS surveys. The first method is the same as the one used in populations with accurate vital statistics and is based on a weighted average of single year of age first birth rates. The second is the singulate mean age at first birth. RESULTS: A comparison of the two estimates obtained from the latest surveys in 62 countries shows excellent agreement in countries in which there is no evidence of a rise in childlessness. But, as expected on theoretical grounds, there is less agreement in populations that have experienced an increase in the proportion childless. CONCLUSIONS: Based on these results, we recommend the first method. The measure is relatively straightforward to calculate and, since it refers to recent births, is presumably more accurately reported than indicators based on events that occurred in the more distant past. This measure makes it possible for the first time to assess recent trends in the onset of childbearing in developing countries with multiple DHS surveys and to compare recent period estimates of the mean age at first birth among countries. PMID- 26379477 TI - Unsuccessful percutaneous mechanical thrombectomy in fibrin-rich high-risk pulmonary thromboembolism. AB - BACKGROUND: We report a case of unsuccessful percutaneous mechanical thrombectomy in treatment of a high-risk pulmonary embolism (PE). Pulmonary thromboemboli are commonly expected as a homogenous mass, rich with red blood cell content, which respond well to percutaneous mechanical thrombectomy (PMT). Catheter-based approach or surgical embolectomy are two treatment options that are usually considered for treatment of high-risk PE when the thrombolytic therapy fails or it is contraindicated due to a patient's persisting hemodynamic compromise. Currently, selection criteria for PE treatment options are based mostly on the assessment of patient's history. The aim of this report is to highlight a possible treatment complication in PMT of structurally heterogeneous thrombotic mass due to PMT inadequacy. CASE PRESENTATION: A 32 year-old male with polytrauma was admitted to an intensive care unit after a right-sided nephrectomy and evacuation of retroperitoneal hematoma. The patient initial haemostatic disorder was improved by administration of blood preparations, an anti-fibrinolytic agent and concentrates of fibrinogen. On the third day he presented sudden onset of hemodynamic instability and was incapable of standard CTA diagnostic procedure. Urgent and relevant investigations including transthoracic and transesophageal echocardiogram confirmed a high-risk PE. PMT was performed due to contraindications for systemic thrombolysis. Long-term PMT was attempted using aspiration with several devices. No major improvement was achieved in any of the treatments and the patient died. Autopsy confirmed a large heterogeneous thrombotic mass in the pulmonary trunk folding to the right main artery. Additional histological analysis revealed a high fibrin-rich content in the peripheral surroundings of the thrombus. CONCLUSION: In the case, it was confirmed that the outcome of PMT was directly influenced by mechanical and histological features of the thromboembolus in high-risk PE. Formation of a rather complex thromboembolus in high-risk PE favors surgical embolectomy as the only life-saving treatment option. Current diagnostic imaging techniques do not enable precise assessment of thrombi structure and are therefore unable to identify patients who might benefit from PMT or open surgical embolectomy. Surgical backup treatment should be considered if there are no contraindications in the event of a failed catheter intervention. PMID- 26379476 TI - The role of phosphodiesterase-5 inhibitors in prostatic inflammation: a review. AB - Clinical and basic experimental evidence indicates that chronic inflammation is the greatest factor in benign prostatic hyperplasia (BPH) progression, which is the most common cause of Lower Urinary Tract Symptoms (LUTS). The use of anti inflammatory agents such as steroids, cyclooxygenase-2 (COX-2) and phytotherapics have been investigated as forms of treatment for various prostate diseases. Recent evidence has demonstrated that PDE5 inhibitors (PDE5Is) improve symptoms of BPH/LUTS, possibly as a result of the relaxing of the smooth muscle fibers of the bladder and prostate by NO/cGMPc signaling, or by improving RhoA/Rho-kinase (ROCK), and reduction of the hyperactivity of the autonomic nervous system. However, some results have suggested that besides vasodilatation and their anti proliferative effect, PDE5Is exert a direct anti-inflammatory effect, by raising cGMP. Given that inflammation is major factor in benign prostatic hyperplasia (BPH) progression, PDE5Is could act also restore prostatic function as they act as potent anti-inflammatory drugs. This review aims to provide a comprehensive summary of the use of phosphodiesterase-5 inhibitors to treat prostatic inflammation. PMID- 26379480 TI - Supervised discriminant analysis for droplet micro-magnetofluidics. AB - We apply the technique of supervised discriminant analysis (SDA) for in-flow detection in droplet-based magnetofluidics. Based on the SDA, we successfully discriminate bivariant droplets of different volumes containing different encapsulated magnetic content produced by a GMR-based lab-on-chip platform. We demonstrate that the accuracy of discrimination is superior when the correlation of variables for data training is included to the case when the spatial distribution of variables is considered. Droplets produced with differences in ferrofluid concentration of 2.5 mg/ml and volume of 200 pl have been identified with high accuracy (98 %), indicating the significance of SDA for e.g. the discrimination in magnetic immuno-agglutination assays. Furthermore, the results open the way for the development of a unique magnetofluidic platform for future applications in multiplexed droplet-based barcoding assays and screening. PMID- 26379481 TI - Interactions between visceral afferent signaling and stimulus processing. AB - Visceral afferent signals to the brain influence thoughts, feelings and behavior. Here we highlight the findings of a set of empirical investigations in humans concerning body-mind interaction that focus on how feedback from states of autonomic arousal shapes cognition and emotion. There is a longstanding debate regarding the contribution of the body to mental processes. Recent theoretical models broadly acknowledge the role of (autonomically-mediated) physiological arousal to emotional, social and motivational behaviors, yet the underlying mechanisms are only partially characterized. Neuroimaging is overcoming this shortfall; first, by demonstrating correlations between autonomic change and discrete patterns of evoked, and task-independent, neural activity; second, by mapping the central consequences of clinical perturbations in autonomic response and; third, by probing how dynamic fluctuations in peripheral autonomic state are integrated with perceptual, cognitive and emotional processes. Building on the notion that an important source of the brain's representation of physiological arousal is derived from afferent information from arterial baroreceptors, we have exploited the phasic nature of these signals to show their differential contribution to the processing of emotionally-salient stimuli. This recent work highlights the facilitation at neural and behavioral levels of fear and threat processing that contrasts with the more established observations of the inhibition of central pain processing during baroreceptors activation. The implications of this body-brain-mind axis are discussed. PMID- 26379482 TI - Cognitive cost as dynamic allocation of energetic resources. AB - While it is widely recognized that thinking is somehow costly, involving cognitive effort and producing mental fatigue, these costs have alternatively been assumed to exist, treated as the brain's assessment of lost opportunities, or suggested to be metabolic but with implausible biological bases. We present a model of cognitive cost based on the novel idea that the brain senses and plans for longer-term allocation of metabolic resources by purposively conserving brain activity. We identify several distinct ways the brain might control its metabolic output, and show how a control-theoretic model that models decision-making with an energy budget can explain cognitive effort avoidance in terms of an optimal allocation of limited energetic resources. The model accounts for both subject responsiveness to reward and the detrimental effects of hypoglycemia on cognitive function. A critical component of the model is using astrocytic glycogen as a plausible basis for limited energetic reserves. Glycogen acts as an energy buffer that can temporarily support high neural activity beyond the rate supported by blood glucose supply. The published dynamics of glycogen depletion and repletion are consonant with a broad array of phenomena associated with cognitive cost. Our model thus subsumes both the "cost/benefit" and "limited resource" models of cognitive cost while retaining valuable contributions of each. We discuss how the rational control of metabolic resources could underpin the control of attention, working memory, cognitive look ahead, and model-free vs. model-based policy learning. PMID- 26379483 TI - The smell of fear: innate threat of 2,5-dihydro-2,4,5-trimethylthiazoline, a single molecule component of a predator odor. AB - In the last several years, the importance of understanding what innate threat and fear is, in addition to learning of threat and fear, has become evident. Odors from predators are ecologically relevant stimuli used by prey animals as warnings for the presence of danger. Of importance, these odors are not necessarily noxious or painful, but they have innate threat-like properties. This review summarizes the progress made on the behavioral and neuroanatomical fundamentals of innate fear of the predator odor, 2,5-dihydro-2,4,5-trimethylthiazoline (TMT), a component of fox feces. TMT is one of several single molecule components of predator odors that have been isolated in the last several years. Isolation of these single molecules has allowed for rapid advances in delineating the behavioral constraints and selective neuroanatomical pathways of predator odor induced fear. In naive mice and rats, TMT induces a number of fear and defensive behaviors, including robust freezing, indicating it is an innate threat stimulus. However, there are a number of behavioral constraints that we do not yet understand. Similarly, while some of the early olfactory sensory pathways for TMT induced fear are being delineated, the pathways from olfactory systems to emotional and motor output regions are less well understood. This review will focus on what we know and what we still need to learn about the behavior and neuroanatomy of TMT-induced fear. PMID- 26379485 TI - Rewiring, forgetting and learning. Commentary: A critical period for experience dependent remodeling of adult-born neuron connectivity. PMID- 26379486 TI - Response: "Commentary: Utility-free heuristic models of two-option choice can mimic predictions of utility-stage models under many conditions". PMID- 26379484 TI - Effects of anabolic-androgens on brain reward function. AB - Androgens are mainly prescribed to treat several diseases caused by testosterone deficiency. However, athletes try to promote muscle growth by manipulating testosterone levels or assuming androgen anabolic steroids (AAS). These substances were originally synthesized to obtain anabolic effects greater than testosterone. Although AAS are rarely prescribed compared to testosterone, their off-label utilization is very wide. Furthermore, combinations of different steroids and doses generally higher than those used in therapy are common. Symptoms of the chronic use of supra-therapeutic doses of AAS include anxiety, depression, aggression, paranoia, distractibility, confusion, amnesia. Interestingly, some studies have shown that AAS elicited electroencephalographic changes similar to those observed with amphetamine abuse. The frequency of side effects is higher among AAS abusers, with psychiatric complications such as labile mood, lack of impulse control and high violence. On the other hand, AAS addiction studies are complex because data collection is very difficult due to the subjects' reticence and can be biased by many variables, including physical exercise, that alter the reward system. Moreover, it has been reported that AAS may imbalance neurotransmitter systems involved in the reward process, leading to increased sensitivity toward opioid narcotics and central stimulants. The goal of this article is to review the literature on steroid abuse and changes to the reward system in preclinical and clinical studies. PMID- 26379487 TI - Low serum sphingolipids in children with attention deficit-hyperactivity disorder. AB - BACKGROUND: Attention deficit-hyperactivity disorder (ADHD) is the most prevalent neuropsychiatric condition in childhood. ADHD is a multifactorial trait with a strong genetic component. One neurodevelopmental hypothesis is that ADHD is associated with a lag in brain maturation. Sphingolipids are essential for brain development and neuronal functioning, but their role in ADHD pathogenesis is unexplored. We hypothesized that serum sphingolipid levels distinguish ADHD patients from unaffected subjects. METHODS: We characterized serum sphingolipid profiles of ADHD patients and two control groups: non-affected relatives and non affected subjects without a family history of ADHD. Sphingolipids were measured by LC-MS/MS in 77 participants (28 ADHD patients, 28 related controls, and 21 unrelated controls). ADHD diagnosis was based on the Diagnostic and Statistical Manual of Mental Disorders (DSM IV-TR). Diagnostic criteria were assessed by two independent observers. Groups were compared by parametrical statistics. RESULTS: Serum sphingomyelins C16:0, C18:0, C18:1, C24:1, ceramide C24:0, and deoxy ceramide C24:1 were significantly decreased in ADHD patients at 20-30% relative reductions. In our sample, decreased serum sphingomyelin levels distinguished ADHD patients with 79% sensitivity and 78% specificity. CONCLUSIONS: Our results showed lower levels of all major serum sphingomyelins in ADHD. These findings may reflect brain maturation and affect neuro-functional pathways characteristic for ADHD. PMID- 26379488 TI - Characterizing donation behavior from psychophysiological indices of narrative experience. AB - Research on narrative persuasion has yet to investigate whether this process influences behavior. The current study explored whether: (1) a narrative could persuade participants to donate to a charity, a prosocial, behavioral decision; (2) psychophysiological metrics can delineate the differences between donation/non-donation behaviors; and (3) donation behavior can be correlated with measures of psychophysiology, self-reported reactions to the narrative, and intrinsic characteristics. Participants (n = 49) completed personality/disposition questionnaires, viewed one of two versions of a narrative while EEG and ECG were recorded, completed a questionnaire regarding their reactions to the narrative, and were given an opportunity to donate to a charity related to the themes of the narrative. Results showed that: (1) 34.7% of participants donated; (2) psychophysiological metrics successfully delineated between donation behaviors and the effects of narrative version; and (3) psychophysiology and reactions to the narrative were better able to explain the variance (88 and 65%, respectively) in the amount donated than all 3 metrics combined as well as any metric alone. These findings demonstrate the promise of narrative persuasion for influencing prosocial, behavioral decisions. Our results also illustrate the utility of the previously stated metrics for understanding and possibly even manipulating behaviors resulting from narrative persuasion. PMID- 26379489 TI - A posteriori model validation for the temporal order of directed functional connectivity maps. AB - A posteriori model validation for the temporal order of neural directed functional connectivity maps is rare. This is striking because models that require sequential independence among residuals are regularly implemented. The aim of the current study was (a) to apply to directed functional connectivity maps of functional magnetic resonance imaging data an a posteriori model validation procedure (i.e., white noise tests of one-step-ahead prediction errors combined with decision criteria for revising the maps based upon Lagrange Multiplier tests), and (b) to demonstrate how the procedure applies to single subject simulated, single-subject task-related, and multi-subject resting state data. Directed functional connectivity was determined by the unified structural equation model family of approaches in order to map contemporaneous and first order lagged connections among brain regions at the group- and individual-levels while incorporating external input, then white noise tests were run. Findings revealed that the validation procedure successfully detected unmodeled sequential dependencies among residuals and recovered higher order (greater than one) simulated connections, and that the procedure can accommodate task-related input. Findings also revealed that lags greater than one were present in resting state data: With a group-level network that contained only contemporaneous and first order connections, 44% of subjects required second order, individual-level connections in order to obtain maps with white noise residuals. Results have broad methodological relevance (e.g., temporal validation is necessary after directed functional connectivity analyses because the presence of unmodeled higher order sequential dependencies may bias parameter estimates) and substantive implications (e.g., higher order lags may be common in resting state data). PMID- 26379490 TI - Prohormone convertase 2 activity is increased in the hippocampus of Wfs1 knockout mice. AB - BACKGROUND: Mutations in WFS1 gene cause Wolfram syndrome, which is a rare autosomal recessive disorder, characterized by diabetes insipidus, diabetes mellitus, optic nerve atrophy, and deafness. The WFS1 gene product wolframin is located in the endoplasmic reticulum. Mice lacking this gene exhibit disturbances in the processing and secretion of peptides, such as vasopressin and insulin. In the brain, high levels of the wolframin protein have been observed in the hippocampus, amygdala, and limbic structures. The aim of this study was to investigate the effect of Wfs1 knockout (KO) on peptide processing in mouse hippocampus. A peptidomic approach was used to characterize individual peptides in the hippocampus of wild-type and Wfs1 KO mice. RESULTS: We identified 126 peptides in hippocampal extracts and the levels of 10 peptides differed between Wfs1 KO and wild-type mice at P < 0.05. The peptide with the largest alteration was little-LEN, which level was 25 times higher in the hippocampus of Wfs1 KO mice compared to wild-type mice. Processing (cleavage) of little-LEN from the Pcsk1n gene product proSAAS involves prohormone convertase 2 (PC2). Thus, PC2 activity was measured in extracts prepared from the hippocampus of Wfs1 KO mice. The activity of PC2 in Wfs1 mutant mice was significantly higher (149.9 +/- 2.3%, p < 0.0001, n = 8) than in wild-type mice (100.0 +/- 7.0%, n = 8). However, Western blot analysis showed that protein levels of 7B2, proPC2 and PC2 were same in both groups, and so were gene expression levels. CONCLUSION: Processing of proSAAS is altered in the hippocampus of Wfs1-KO mice, which is caused by increased activity of PC2. Increased activity of PC2 in Wfs1 KO mice is not caused by alteration in the levels of PC2 protein. Our results suggest a functional link between Wfs1 and PC2. Thus, the detailed molecular mechanism of the role of Wfs1 in the regulation of PC2 activity needs further investigation. PMID- 26379492 TI - Developmental axon stretch stimulates neuron growth while maintaining normal electrical activity, intracellular calcium flux, and somatic morphology. AB - Elongation of nerve fibers intuitively occurs throughout mammalian development, and is synchronized with expansion of the growing body. While most tissue systems enlarge through mitosis and differentiation, elongation of nerve fibers is remarkably unique. The emerging paradigm suggests that axons undergo stretch as contiguous tissues enlarge between the proximal and distal segments of spanning nerve fibers. While stretch is distinct from growth, tension is a known stimulus which regulates the growth of axons. Here, we hypothesized that the axon stretch growth process may be a natural form of injury, whereby regenerative processes fortify elongating axons in order to prevent disconnection. Harnessing the live imaging capability of our axon stretch-growth bioreactors, we assessed neurons both during and following stretch for biomarkers associated with injury. Utilizing whole-cell patch clamp recording, we found no evidence of changes in spontaneous action potential activity or degradation of elicited action potentials during real-time axon stretch at strains of up to 18% applied over 5 min. Unlike traumatic axonal injury, functional calcium imaging of the soma revealed no shifts in free intracellular calcium during axon stretch. Finally, the cross-sectional areas of nuclei and cytoplasms were normal, with no evidence of chromatolysis following week-long stretch-growth limited to the lower of 25% strain or 3 mm total daily stretch. The neuronal growth cascade coupled to stretch was concluded to be independent of the changes in membrane potential, action potential generation, or calcium flux associated with traumatic injury. While axon stretch-growth is likely to share overlap with regenerative processes, we conclude that developmental stretch is a distinct stimulus from traumatic axon injury. PMID- 26379491 TI - A new perspective on the role of the CREB family of transcription factors in memory consolidation via adult hippocampal neurogenesis. AB - Adult neurogenesis is the process by which new neurons are generated in the brains of adults. Since its discovery 50 years ago, adult neurogenesis has been widely studied in the mammalian brain and has provided a new perspective on the pathophysiology of many psychiatric and neurodegenerative disorders, some of which affect memory. In this regard, adult hippocampal neurogenesis (AHN), which occurs in the subgranular zone (SGZ) of the dentate gyrus (DG), has been suggested to play a role in the formation and consolidation of new memories. This process involves many transcription factors, of which cyclic AMP (cAMP) responsive element-binding protein (CREB) is a well-documented one. In the developing brain, CREB regulates crucial cell stages (e.g., proliferation, differentiation, and survival), and in the adult brain, it participates in neuronal plasticity, learning, and memory. In addition, new evidence supports the hypothesis that CREB may also participate in learning and memory through its involvement in AHN. This review examines the CREB family of transcription factors, including the different members and known signaling pathways. It highlights the role of CREB as a modulator of AHN, which could underlie its function in memory consolidation mechanisms. PMID- 26379493 TI - Cell-type-specific tuning of Cav1.3 Ca(2+)-channels by a C-terminal automodulatory domain. AB - Cav1.3 L-type Ca(2+)-channel function is regulated by a C-terminal automodulatory domain (CTM). It affects channel binding of calmodulin and thereby tunes channel activity by interfering with Ca(2+)- and voltage-dependent gating. Alternative splicing generates short C-terminal channel variants lacking the CTM resulting in enhanced Ca(2+)-dependent inactivation and stronger voltage-sensitivity upon heterologous expression. However, the role of this modulatory domain for channel function in its native environment is unkown. To determine its functional significance in vivo, we interrupted the CTM with a hemagglutinin tag in mutant mice (Cav1.3DCRD(HA/HA)). Using these mice we provide biochemical evidence for the existence of long (CTM-containing) and short (CTM-deficient) Cav1.3 alpha1 subunits in brain. The long (HA-labeled) Cav1.3 isoform was present in all ribbon synapses of cochlear inner hair cells. CTM-elimination impaired Ca(2+)-dependent inactivation of Ca(2+)-currents in hair cells but increased it in chromaffin cells, resulting in hyperpolarized resting potentials and reduced pacemaking. CTM disruption did not affect hearing thresholds. We show that the modulatory function of the CTM is affected by its native environment in different cells and thus occurs in a cell-type specific manner in vivo. It stabilizes gating properties of Cav1.3 channels required for normal electrical excitability. PMID- 26379495 TI - HSP70 mediates survival in apoptotic cells-Boolean network prediction and experimental validation. AB - Neuronal stress or injury results in the activation of proteins, which regulate the balance between survival and apoptosis. However, the complex mechanism of cell signaling involving cell death and survival, activated in response to cellular stress is not yet completely understood. To bring more clarity about these mechanisms, a Boolean network was constructed that represented the apoptotic pathway in neuronal cells. FasL and neurotrophic growth factor (NGF) were considered as inputs in the absence and presence of heat shock proteins known to shift the balance toward survival by rescuing pro-apoptotic cells. The probabilities of survival, DNA repair and apoptosis as cellular fates, in the presence of either the growth factor or FasL, revealed a survival bias encoded in the network. Boolean predictions tested by measuring the mRNA level of caspase-3, caspase-8, and BAX in neuronal Neuro2a (N2a) cell line with NGF and FasL as external input, showed positive correlation with the observed experimental results for survival and apoptotic states. It was observed that HSP70 contributed more toward rescuing cells from apoptosis in comparison to HSP27, HSP40, and HSP90. Overexpression of HSP70 in N2a transfected cells showed reversal of cellular fate from FasL-induced apoptosis to survival. Further, the pro-survival role of the proteins BCL2, IAP, cFLIP, and NFkappaB determined by vertex perturbation analysis was experimentally validated through protein inhibition experiments using EM20-25, Embelin and Wedelolactone, which resulted in 1.27-, 1.26-, and 1.46-fold increase in apoptosis of N2a cells. The existence of a one to-one correspondence between cellular fates and attractor states shows that Boolean networks may be employed with confidence in qualitative analytical studies of biological networks. PMID- 26379496 TI - In vivo characterization of microglial engulfment of dying neurons in the zebrafish spinal cord. AB - Microglia are specialized phagocytes in the vertebrate central nervous system (CNS). As the resident immune cells of the CNS they play an important role in the removal of dying neurons during both development and in several neuronal pathologies. Microglia have been shown to prevent the diffusion of damaging degradation products of dying neurons by engulfment and ingestion. Here we describe a live imaging approach that uses UV laser ablation to selectively stress and kill spinal neurons and visualize the clearance of neuronal remnants by microglia in the zebrafish spinal cord. In vivo imaging confirmed the motile nature of microglia within the uninjured spinal cord. However, selective neuronal ablation triggered rapid activation of microglia, leading to phagocytic uptake of neuronal debris by microglia within 20-30 min. This process of microglial engulfment is highly dynamic, involving the extension of processes toward the lesion site and consequently the ingestion of the dying neuron. 3D rendering analysis of time-lapse recordings revealed the formation of phagosome-like structures in the activated microglia located at the site of neuronal ablation. This real-time representation of microglial phagocytosis in the living zebrafish spinal cord provides novel opportunities to study the mechanisms of microglia mediated neuronal clearance. PMID- 26379497 TI - Lipidome of midbody released from neural stem and progenitor cells during mammalian cortical neurogenesis. AB - Midbody release from proliferative neural progenitor cells is tightly associated with the neuronal commitment of neural progenitor cells during the progression of neurogenesis in the mammalian cerebral cortex. While the central portion of the midbody, a cytoplasmic bridge between nascent daughter cells, is engulfed by one of the daughter cell by most cells in vitro, it is shown to be released into the extracellular cerebrospinal fluid (CF) in vivo in mouse embryos. Several proteins have been involved in midbody release; however, few studies have addressed the participation of the plasma membrane's lipids in this process. Here, we show by Shotgun Lipidomic analysis that phosphatydylserine (PS), among other lipids, is enriched in the released midbodies compared to lipoparticles and cellular membranes, both collected from the CF of the developing mouse embryos. Moreover, the developing mouse embryo neural progenitor cells released two distinct types of midbodies carrying either internalized PS or externalized PS on their membrane. This strongly suggests that phagocytosis and an alternative fate of released midbodies exists. HeLa cells, which are known to mainly engulf the midbody show almost no PS exposure, if any, on the outer leaflet of the midbody membrane. These results point toward that PS exposure might be involved in the selection of recipients of released midbodies, either to be engulfed by daughter cells or phagocytosed by non-daughter cells or another cell type in the developing cerebral cortex. PMID- 26379494 TI - Gene expression parallels synaptic excitability and plasticity changes in Alzheimer's disease. AB - Alzheimer's disease (AD) is a neurodegenerative disorder characterized by abnormal accumulation of beta-amyloid and tau and synapse dysfunction in memory related neural circuits. Pathological and functional changes in the medial temporal lobe, a region essential for explicit memory encoding, contribute to cognitive decline in AD. Surprisingly, functional imaging studies show increased activity of the hippocampus and associated cortical regions during memory tasks in presymptomatic and early AD stages, whereas brain activity declines as the disease progresses. These findings suggest an emerging scenario where early pathogenic events might increase neuronal excitability leading to enhanced brain activity before clinical manifestations of the disease, a stage that is followed by decreased brain activity as neurodegeneration progresses. The mechanisms linking pathology with synaptic excitability and plasticity changes leading to memory loss in AD remain largely unclear. Recent studies suggest that increased brain activity parallels enhanced expression of genes involved in synaptic transmission and plasticity in preclinical stages, whereas expression of synaptic and activity-dependent genes are reduced by the onset of pathological and cognitive symptoms. Here, we review recent evidences indicating a relationship between transcriptional deregulation of synaptic genes and neuronal activity and memory loss in AD and mouse models. These findings provide the basis for potential clinical applications of memory-related transcriptional programs and their regulatory mechanisms as novel biomarkers and therapeutic targets to restore brain function in AD and other cognitive disorders. PMID- 26379498 TI - Long term ex vivo culturing of Drosophila brain as a method to live image pupal brains: insights into the cellular mechanisms of neuronal remodeling. AB - Holometabolous insects, including Drosophila melanogaster, undergo complete metamorphosis that includes a pupal stage. During metamorphosis, the Drosophila nervous system undergoes massive remodeling and growth, that include cell death and large-scale axon and synapse elimination as well as neurogenesis, developmental axon regrowth, and formation of new connections. Neuronal remodeling is an essential step in the development of vertebrate and invertebrate nervous systems. Research on the stereotypic remodeling of Drosophila mushroom body (MB) gamma neurons has contributed to our knowledge of the molecular mechanisms of remodeling but our knowledge of the cellular mechanisms remain poorly understood. A major hurdle in understanding various dynamic processes that occur during metamorphosis is the lack of time-lapse resolution. The pupal case and opaque fat bodies that enwrap the central nervous system (CNS) make live imaging of the central brain in-vivo impossible. We have established an ex vivo long-term brain culture system that supports the development and neuronal remodeling of pupal brains. By optimizing culture conditions and dissection protocols, we have observed development in culture at kinetics similar to what occurs in vivo. Using this new method, we have obtained the first time-lapse sequence of MB gamma neurons undergoing remodeling in up to a single cell resolution. We found that axon pruning is initiated by blebbing, followed by one two nicks that seem to initiate a more widely spread axon fragmentation. As such, we have set up some of the tools and methodologies needed for further exploration of the cellular mechanisms of neuronal remodeling, not limited to the MB. The long-term ex vivo brain culture system that we report here could be used to study dynamic aspects of neurodevelopment of any Drosophila neuron. PMID- 26379499 TI - Oligodendroglial Argonaute protein Ago2 associates with molecules of the Mbp mRNA localization machinery and is a downstream target of Fyn kinase. AB - Oligodendrocytes myelinate neuronal axons in the central nervous system (CNS) facilitating rapid transmission of action potentials by saltatory conduction. Myelin basic protein (MBP) is an essential component of myelin and its absence results in severe hypomyelination in the CNS of rodents. Mbp mRNA is not translated immediately after exit from the nucleus in the cytoplasm, but is transported to the plasma membrane in RNA transport granules in a translationally silenced state. We have previously identified the small non-coding RNA 715 (sncRNA715) as an inhibitor of Mbp translation associated with RNA granules. Argonaute (Ago) proteins and small RNAs form the minimal core of the RNA induced silencing complex and together recognize target mRNAs to be translationally inhibited or degraded. Recently, tyrosine phosphorylation of Ago2 was reported to be a regulator of small RNA binding. The oligodendroglial non-receptor tyrosine kinase Fyn is activated by neuronal signals and stimulates the translation of Mbp mRNA at the axon-glial contact site. Here we analyzed the expression of Ago proteins in oligodendrocytes, if they associate with Mbp mRNA transport granules and are tyrosine phosphorylated by Fyn. We show that all Ago proteins (Ago1-4) are expressed by oligodendrocytes and that Ago2 colocalizes with hnRNP A2 in granular cytoplasmic structures. Ago2 associates with hnRNP A2, Mbp mRNA, sncRNA715 and Fyn kinase and is tyrosine phosphorylated in response to Fyn activity. Our findings suggest an involvement of Ago2 in the translational regulation of Mbp. The identification of Ago proteins as Fyn targets will foster further research to understand in more molecular detail how Fyn activity regulates Mbp translation. PMID- 26379500 TI - Effects of bone marrow mesenchymal stem cells (BM-MSCs) on rat pial microvascular remodeling after transient middle cerebral artery occlusion. AB - Previous studies have shown that the pial microcirculation remodeling improves neurological outcome after middle cerebral artery occlusion (MCAO), accompanied by higher expression of vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS), modulating in vivo angiogenesis. This study was aimed to assess the effects of bone marrow mesenchymal stem cells (BM-MSCs) infused after MCAO on rat pial microcirculation. Animals were subjected to 2 h MCAO followed by BM-MSCs infusion into internal carotid artery. Pial microcirculation was observed at different reperfusion times by fluorescence microscopy. Geometric characteristics of arteriolar networks, permeability increase, leukocyte adhesion, perfused capillary density, VEGF, and endothelial nitric oxide synthase (e-NOS) expression were evaluated. Green fluorescent protein (GFP)-BM-MSCs were used to evaluate their distribution and cell phenotype development during reperfusion. BM-MSCs stimulated a geometric rearrangement of pial networks with formation of new anastomotic vessels sprouting from preexistent arterioles in the penumbra at 7-14-28 days of reperfusion. At the same time VEGF and eNOS expression increased. GFP-BM-MSCs appear to be involved in endothelial and smooth muscle cell programming in the infarcted area. In conclusion, transient MCAO induced pial vascular remodeling characterized by arteriolar anastomotic arcades (originated from preexistent arterioles in penumbra area) able to overlap the ischemic core supplying blood to the neuronal tissue. BM-MSCs appear to accelerate angiogenic processes facilitating new vessel formation; this mechanism was promoted by an increase in VEGF and eNOS expression. PMID- 26379501 TI - Blockade of pathological retinal ganglion cell hyperactivity improves optogenetically evoked light responses in rd1 mice. AB - Retinitis pigmentosa (RP) is a progressive retinal dystrophy that causes visual impairment and eventual blindness. Retinal prostheses are the best currently available vision-restoring treatment for RP, but only restore crude vision. One possible contributing factor to the poor quality of vision achieved with prosthetic devices is the pathological retinal ganglion cell (RGC) hyperactivity that occurs in photoreceptor dystrophic disorders. Gap junction blockade with meclofenamic acid (MFA) was recently shown to diminish RGC hyperactivity and improve the signal-to-noise ratio (SNR) of RGC responses to light flashes and electrical stimulation in the rd10 mouse model of RP. We sought to extend these results to spatiotemporally patterned optogenetic stimulation in the faster degenerating rd1 model and compare the effectiveness of a number of drugs known to disrupt rd1 hyperactivity. We crossed rd1 mice with a transgenic mouse line expressing the light-sensitive cation channel channelrhodopsin2 (ChR2) in RGCs, allowing them to be stimulated directly using high-intensity blue light. We used 60-channel ITO multielectrode arrays to record ChR2-mediated RGC responses from wholemount, ex-vivo retinas to full-field and patterned stimuli before and after application of MFA, 18-beta-glycyrrhetinic acid (18BGA, another gap junction blocker) or flupirtine (Flu, a Kv7 potassium channel opener). All three drugs decreased spontaneous RGC firing, but 18BGA and Flu also decreased the sensitivity of RGCs to optogenetic stimulation. Nevertheless, all three drugs improved the SNR of ChR2-mediated responses. MFA also made it easier to discern motion direction of a moving bar from RGC population responses. Our results support the hypothesis that reduction of pathological RGC spontaneous activity characteristic in retinal degenerative disorders may improve the quality of visual responses in retinal prostheses and they provide insights into how best to achieve this for optogenetic prostheses. PMID- 26379502 TI - Dynamic DNA methylation in the brain: a new epigenetic mark for experience dependent plasticity. AB - Experience-dependent plasticity is the ability of brain circuits to undergo molecular, structural and functional changes as a function of neural activity. Neural activity continuously shapes our brain during all the stages of our life, from infancy through adulthood and beyond. Epigenetic modifications of histone proteins and DNA seem to be a leading molecular mechanism to modulate the transcriptional changes underlying the fine-tuning of synaptic connections and circuitry rewiring during activity-dependent plasticity. The recent discovery that cytosine methylation is an epigenetic mark particularly dynamic in brain cells has strongly increased the interest of neuroscientists in understanding the role of covalent modifications of DNA in activity-induced remodeling of neuronal circuits. Here, we provide an overview of the role of DNA methylation and hydroxylmethylation in brain plasticity both during adulthood, with emphasis on learning and memory related processes, and during postnatal development, focusing specifically on experience-dependent plasticity in the visual cortex. PMID- 26379503 TI - Cdc42 and RhoA reveal different spatio-temporal dynamics upon local stimulation with Semaphorin-3A. AB - Small RhoGTPases, such as Cdc42 and RhoA, are key players in integrating external cues and intracellular signaling pathways that regulate growth cone (GC) motility. Indeed, Cdc42 is involved in actin polymerization and filopodia formation, whereas RhoA induces GC collapse and neurite retraction through actomyosin contraction. In this study we employed Forster Resonance Energy Transfer (FRET) microscopy to study the spatio-temporal dynamics of Cdc42 and RhoA in GCs in response to local Semaphorin-3A (Sema3A) stimulation obtained with lipid vesicles filled with Sema3A and positioned near the selected GC using optical tweezers. We found that Cdc42 and RhoA were activated at the leading edge of NG108-15 neuroblastoma cells during spontaneous cycles of protrusion and retraction, respectively. The release of Sema3A brought to a progressive activation of RhoA within 30 s from the stimulus in the central region of the GC that collapsed and retracted. In contrast, the same stimulation evoked waves of Cdc42 activation propagating away from the stimulated region. A more localized stimulation obtained with Sema3A coated beads placed on the GC, led to Cdc42 active waves that propagated in a retrograde manner with a mean period of 70 s, and followed by GC retraction. Therefore, Sema3A activates both Cdc42 and RhoA with a complex and different spatial-temporal dynamics. PMID- 26379504 TI - Editorial: Stem cells and progenitor cells in ischemic stroke-fashion or future? PMID- 26379507 TI - Corrigendum: An electromechanical model of neuronal dynamics using Hamilton's principle. PMID- 26379506 TI - Modular and coordinated expression of immune system regulatory and signaling components in the developing and adult nervous system. AB - During development, the nervous system (NS) is assembled and sculpted through a concerted series of neurodevelopmental events orchestrated by a complex genetic programme. While neural-specific gene expression plays a critical part in this process, in recent years, a number of immune-related signaling and regulatory components have also been shown to play key physiological roles in the developing and adult NS. While the involvement of individual immune-related signaling components in neural functions may reflect their ubiquitous character, it may also reflect a much wider, as yet undescribed, genetic network of immune-related molecules acting as an intrinsic component of the neural-specific regulatory machinery that ultimately shapes the NS. In order to gain insights into the scale and wider functional organization of immune-related genetic networks in the NS, we examined the large scale pattern of expression of these genes in the brain. Our results show a highly significant correlated expression and transcriptional clustering among immune-related genes in the developing and adult brain, and this correlation was the highest in the brain when compared to muscle, liver, kidney and endothelial cells. We experimentally tested the regulatory clustering of immune system (IS) genes by using microarray expression profiling in cultures of dissociated neurons stimulated with the pro-inflammatory cytokine TNF-alpha, and found a highly significant enrichment of immune system-related genes among the resulting differentially expressed genes. Our findings strongly suggest a coherent recruitment of entire immune-related genetic regulatory modules by the neural-specific genetic programme that shapes the NS. PMID- 26379505 TI - SOD1 misplacing and mitochondrial dysfunction in amyotrophic lateral sclerosis pathogenesis. AB - Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease presenting as sporadic (sALS) or familial (fALS) forms. Even if the list of the genes underlining ALS greatly expanded, defects in superoxide dismutase 1 (SOD1), encoding the copper/zinc SOD1, still remain a major cause of fALS and are likely involved also in apparently sporadic presentations. The pathogenesis of ALS is still unknown, but several lines of evidence indicate that the mitochondrial accumulation of mutant SOD1 is an important mechanism of mitochondrial dysfunction, leading to motor neuron pathology and death. The intramitochondrial localization of mutant SOD1 is debated. Mutant SOD1 might accumulate inside the intermembrane space (IMS), overriding the physiological retention regulated by the copper chaperone for superoxide dismutase (CCS). On the other hand, misfolded SOD1 might deposit onto the outer mitochondrial membrane (OMM), clumping the transport across mitochondrial membranes and engaging mitochondrial-dependent cell apoptosis. The elucidation of the mechanisms ruling SOD1 localization and misplacing might shed light on peculiar ALS features such as cell selectivity and late onset. More importantly, these studies might disclose novel targets for therapeutic intervention in familial ALS as well as non-genetic forms. Finally, pharmacological or genetic manipulation aimed to prevent or counteract the intracellular shifting of mutant SOD1 could be effective for other neurodegenerative disorders featuring the toxic accumulation of misfolded proteins. PMID- 26379508 TI - Periodotopy in the gerbil inferior colliculus: local clustering rather than a gradient map. AB - Periodicities in sound waveforms are widespread, and shape important perceptual attributes of sound including rhythm and pitch. Previous studies have indicated that, in the inferior colliculus (IC), a key processing stage in the auditory midbrain, neurons tuned to different periodicities might be arranged along a periodotopic axis which runs approximately orthogonal to the tonotopic axis. Here we map out the topography of frequency and periodicity tuning in the IC of gerbils in unprecedented detail, using pure tones and different periodic sounds, including click trains, sinusoidally amplitude modulated (SAM) noise and iterated rippled noise. We found that while the tonotopic map exhibited a clear and highly reproducible gradient across all animals, periodotopic maps varied greatly across different types of periodic sound and from animal to animal. Furthermore, periodotopic gradients typically explained only about 10% of the variance in modulation tuning between recording sites. However, there was a strong local clustering of periodicity tuning at a spatial scale of ca. 0.5 mm, which also differed from animal to animal. PMID- 26379510 TI - Harvesting of olfactory ensheathing cells for autologous transplantation into the spinal cord injury. Its complexity in dogs. PMID- 26379509 TI - Prenatal and acute cocaine exposure affects neural responses and habituation to visual stimuli. AB - Psychostimulants have many effects on visual function, from adverse following acute and prenatal exposure to therapeutic on attention deficit. To determine the impact of prenatal and acute cocaine exposure on visual processing, we studied neuronal responses to visual stimuli in two brain regions of a transgenic larval zebrafish expressing the calcium indicator GCaMP-HS. We found that both red light (LF) and dark (DF) flashes elicited similar responses in the optic tectum neuropil (TOn), while the dorsal telencephalon (dTe) responded only to LF. Acute cocaine (0.5 MUM) reduced neuronal responses to LF in both brain regions but did not affect responses to DF. Repeated stimulus presentation (RSP) led to habituation of dTe neurons to LF. Acute cocaine prevented habituation. TOn habituated to DF, but not LF, and DF habituation was not modified by cocaine. Remarkably, prenatal cocaine exposure (PCE) prevented the effects of acute cocaine on LF response amplitude and habituation later in development in both brain regions, but did not affect DF responses. We discovered that, in spite of similar neural responses to LF and DF in the TO (superior colliculus in mammals), responses to LF are more complex, involving dTe (homologous to the cerebral cortex), and are more vulnerable to cocaine. Our results demonstrate that acute cocaine exposure affects visual processing differentially by brain region, and that PCE modifies zebrafish visual processing in multiple structures in a stimulus-dependent manner. These findings are in accordance with the major role that the optic tectum and cerebral cortex play in sustaining visual attention, and support the hypothesis that modification of these areas by PCE may be responsible for visual deficits noted in humans. This model offers new methodological approaches for studying the adverse and therapeutic effects of psychostimulants on attention, and for the development of new pharmacological interventions. PMID- 26379511 TI - Abnormal surface morphology of the central sulcus in children with attention deficit/hyperactivity disorder. AB - The central sulcus (CS) divides the primary motor and somatosensory areas, and its three-dimensional (3D) anatomy reveals the structural changes of the sensorimotor regions. Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that is associated with sensorimotor and executive function deficits. However, it is largely unknown whether the morphology of the CS alters due to inappropriate development in the ADHD brain. Here, we employed the sulcus-based morphometry approach to investigate the 3D morphology of the CS in 42 children whose ages spanned from 8.8 to 13.5 years (21 with ADHD and 21 controls). After automatic labeling of each CS, we computed seven regional shape metrics for each CS, including the global average length, average depth, maximum depth, average span, surface area, average cortical thickness, and local sulcal profile. We found that the average depth and maximum depth of the left CS as well as the average cortical thickness of bilateral CS in the ADHD group were significantly larger than those in the healthy children. Moreover, significant between-group differences in the sulcal profile had been found in middle sections of the CSs bilaterally, and these changes were positively correlated with the hyperactivity-impulsivity scores in the children with ADHD. Altogether, our results provide evidence for the abnormity of the CS anatomical morphology in children with ADHD due to the structural changes in the motor cortex, which significantly contribute to the clinical symptomatology of the disorder. PMID- 26379512 TI - The autistic brain in the context of normal neurodevelopment. AB - The etiology of autism spectrum disorders (ASDs) is complex and largely unclear. Among various lines of inquiry, many have suggested convergence onto disruptions in both neural circuitry and immune regulation/glial cell function pathways. However, the interpretation of the relationship between these two putative mechanisms has largely focused on the role of exogenous factors and insults, such as maternal infection, in activating immune pathways that in turn result in neural network abnormalities. Yet, given recent insights into our understanding of human neurodevelopment, and in particular the critical role of glia and the immune system in normal brain development, it is important to consider these putative pathological processes in their appropriate normal neurodevelopmental context. In this review, we explore the hypothesis that the autistic brain cellular phenotype likely represents intrinsic abnormalities of glial/immune processes constitutively operant in normal brain development that result in the observed neural network dysfunction. We review recent studies demonstrating the intercalated role of neural circuit development, the immune system, and glial cells in the normal developing brain, and integrate them with studies demonstrating pathological alterations in these processes in autism. By discussing known abnormalities in the autistic brain in the context of normal brain development, we explore the hypothesis that the glial/immune component of ASD may instead be related to intrinsic exaggerated/abnormal constitutive neurodevelopmental processes such as network pruning. Moreover, this hypothesis may be relevant to other neurodevelopmental disorders that share genetic, pathologic, and clinical features with autism. PMID- 26379514 TI - Global segregation of cortical activity and metastable dynamics. AB - Cortical activity exhibits persistent metastable dynamics. Assemblies of neurons transiently couple (integrate) and decouple (segregate) at multiple spatiotemporal scales; both integration and segregation are required to support metastability. Integration of distant brain regions can be achieved through long range excitatory projections, but the mechanism supporting long range segregation is not clear. We argue that the thalamocortical matrix connections, which project diffusely from the thalamus to the cortex and have long been thought to support cortical gain control, play an equally-important role in cortical segregation. We present a computational model of the diffuse thalamocortical loop, called the competitive cross-coupling (CXC) spiking network. Simulations of the model show how different levels of tonic input from the brainstem to the thalamus could control dynamical complexity in the cortex, directing transitions between sleep, wakefulness and high attention or vigilance. The model also explains how mutually exclusive activity could arise across large portions of the cortex, such as between the default-mode and task-positive networks. It is robust to noise but does not require noise to autonomously generate metastability. We conclude that the long range segregation observed in brain activity and required for global metastable dynamics could be provided by the thalamocortical matrix, and is strongly modulated by brainstem input to the thalamus. PMID- 26379513 TI - A multi-pathway hypothesis for human visual fear signaling. AB - A hypothesis is proposed for five visual fear signaling pathways in humans, based on an analysis of anatomical connectivity from primate studies and human functional connectvity and tractography from brain imaging studies. Earlier work has identified possible subcortical and cortical fear pathways known as the "low road" and "high road," which arrive at the amygdala independently. In addition to a subcortical pathway, we propose four cortical signaling pathways in humans along the visual ventral stream. All four of these traverse through the LGN to the visual cortex (VC) and branching off at the inferior temporal area, with one projection directly to the amygdala; another traversing the orbitofrontal cortex; and two others passing through the parietal and then prefrontal cortex, one excitatory pathway via the ventral-medial area and one regulatory pathway via the ventral-lateral area. These pathways have progressively longer propagation latencies and may have progressively evolved with brain development to take advantage of higher-level processing. Using the anatomical path lengths and latency estimates for each of these five pathways, predictions are made for the relative processing times at selective ROIs and arrival at the amygdala, based on the presentation of a fear-relevant visual stimulus. Partial verification of the temporal dynamics of this hypothesis might be accomplished using experimental MEG analysis. Possible experimental protocols are suggested. PMID- 26379515 TI - A neurophenomenological model for the role of the hippocampus in temporal consciousness. Evidence from confabulation. AB - Confabulation, the production of statements or actions that are unintentionally incongruous to the subject's history, background, present and future situation, is a rather infrequent disorder with different aetiologies and anatomical lesions. Although they may differ in many ways, confabulations show major similarities. Their content, with some minor exceptions, is plausible and therefore indistinguishable from true memories, unless one is familiar with the patient's history, background, present and future situation. They extend through the whole individuals' temporality, including their past, present and future. Accordingly, we have proposed that rather than a mere memory disorder; confabulation reflects a distortion of Temporal Consciousness (TC), i.e., a specific form of consciousness that allows individuals to locate objects and events according to their subjective temporality. Another feature that confabulators share is that, regardless of their lesion's location, they all have a relatively preserved hippocampus (Hip), at least unilaterally. In this article, we review data showing differences and similarities among forms of confabulation. We then describe a model showing that the hippocampus is crucial both for the normal functioning of TC and as the generator of confabulations, and that different types of confabulation can be traced back to a distortion of TC resulting from damage or disconnection of brain areas directly or indirectly connected to the hippocampus. We conclude by comparing our model with other models of memory and confabulation. PMID- 26379516 TI - The olfactory hole-board test in rats: a new paradigm to study aversion and preferences to odors. AB - Odors of biological relevance (e.g., predator odors, sex odors) are known to effectively influence basic survival needs of rodents such as anti-predatory defensiveness and mating behaviors. Research focused on the effects of these odors on rats' behavior mostly includes multi-trial paradigms where animals experience single odor exposures in subsequent, separated experimental sessions. In the present study, we introduce a modification of the olfactory hole-board test that allows studying the effects of different odors on rats' behavior within single trials. First, we demonstrated that the corner holes of the hole-board were preferentially visited by rats. The placement of different odors under the corner holes changed this hole preference. We showed that holes with carnivore urine samples were avoided, while corner holes with female rat urine samples were preferred. Furthermore, corner holes with urine samples from a carnivore, herbivore, and omnivore were differentially visited indicating that rats can discriminate these odors. To test whether anxiolytic treatment specifically modulates the avoidance of carnivore urine holes, we treated rats with buspirone. Buspirone treatment completely abolished the avoidance of carnivore urine holes. Taken together, our findings indicate that the olfactory hole-board test is a valuable tool for measuring avoidance and preference responses to biologically relevant odors. PMID- 26379517 TI - Editorial: Oxytocin's routes in social behavior: into the 21st century. PMID- 26379518 TI - Modeling choice and reaction time during arbitrary visuomotor learning through the coordination of adaptive working memory and reinforcement learning. AB - Current learning theory provides a comprehensive description of how humans and other animals learn, and places behavioral flexibility and automaticity at heart of adaptive behaviors. However, the computations supporting the interactions between goal-directed and habitual decision-making systems are still poorly understood. Previous functional magnetic resonance imaging (fMRI) results suggest that the brain hosts complementary computations that may differentially support goal-directed and habitual processes in the form of a dynamical interplay rather than a serial recruitment of strategies. To better elucidate the computations underlying flexible behavior, we develop a dual-system computational model that can predict both performance (i.e., participants' choices) and modulations in reaction times during learning of a stimulus-response association task. The habitual system is modeled with a simple Q-Learning algorithm (QL). For the goal directed system, we propose a new Bayesian Working Memory (BWM) model that searches for information in the history of previous trials in order to minimize Shannon entropy. We propose a model for QL and BWM coordination such that the expensive memory manipulation is under control of, among others, the level of convergence of the habitual learning. We test the ability of QL or BWM alone to explain human behavior, and compare them with the performance of model combinations, to highlight the need for such combinations to explain behavior. Two of the tested combination models are derived from the literature, and the latter being our new proposal. In conclusion, all subjects were better explained by model combinations, and the majority of them are explained by our new coordination proposal. PMID- 26379519 TI - Assessment and rehabilitation of neglect using virtual reality: a systematic review. AB - After experiencing a stroke in the right hemisphere, almost 50% of patients showed Unilateral Spatial Neglect (USN). In recent decades, Virtual Reality (VR) has been used as an effective tool both for the assessment and rehabilitation of USN. Indeed, this advanced technology allows post-stroke patients to interact with ecological and engaging environments similar to real ones, but in a safe and controlled way. To provide an overview of the most recent VR applications for the assessment and rehabilitation of USN, a systematic review has been carried out. Since 2010, 13 studies have proposed and tested innovative VR tools for USN. After a wide description of the selected studies, we discuss the main features of these VR tools in order to provide crucial indications for future studies, neurorehabilitation interventions, and clinical practice. PMID- 26379520 TI - Early adversity disrupts the adult use of aversive prediction errors to reduce fear in uncertainty. AB - Early life adversity increases anxiety in adult rodents and primates, and increases the risk for developing post-traumatic disorder (PTSD) in humans. We hypothesized that early adversity impairs the use of learning signals -negative, aversive prediction errors-to reduce fear in uncertainty. To test this hypothesis, we gave adolescent rats a battery of adverse experiences then assessed adult performance in probabilistic Pavlovian fear conditioning and fear extinction. Rats were confronted with three cues associated with different probabilities of foot shock: one cue never predicted shock, another cue predicted shock with uncertainty, and a final cue always predicted shock. Control rats initially acquired fear to all cues, but rapidly reduced fear to the non predictive and uncertain cues. Early adversity rats were slower to reduce fear to the non-predictive cue and never fully reduced fear to the uncertain cue. In extinction, all cues were presented in the absence of shock. Fear to the uncertain cue in discrimination, but not early adversity itself, predicted the reduction of fear in extinction. These results demonstrate early adversity impairs the use of negative aversive prediction errors to reduce fear, especially in situations of uncertainty. PMID- 26379521 TI - A pilot study investigating changes in neural processing after mindfulness training in elite athletes. AB - The ability to pay close attention to the present moment can be a crucial factor for performing well in a competitive situation. Training mindfulness is one approach to potentially improve elite athletes' ability to focus their attention on the present moment. However, virtually nothing is known about whether these types of interventions alter neural systems that are important for optimal performance. This pilot study examined whether an intervention aimed at improving mindfulness [Mindful Performance Enhancement, Awareness and Knowledge (mPEAK)] changes neural activation patterns during an interoceptive challenge. Participants completed a task involving anticipation and experience of loaded breathing during functional magnetic resonance imaging recording. There were five main results following mPEAK training: (1) elite athletes self-reported higher levels of interoceptive awareness and mindfulness and lower levels of alexithymia; (2) greater insula and anterior cingulate cortex (ACC) activation during anticipation and post-breathing load conditions; (3) increased ACC activation during the anticipation condition was associated with increased scores on the describing subscale of the Five Facet Mindfulness Questionnaire; (4) increased insula activation during the post-load condition was associated with decreases in the Toronto Alexithymia Scale identifying feelings subscale; (5) decreased resting state functional connectivity between the PCC and the right medial frontal cortex and the ACC. Taken together, this pilot study suggests that mPEAK training may lead to increased attention to bodily signals and greater neural processing during the anticipation and recovery from interoceptive perturbations. This association between attention to and processing of interoceptive afferents may result in greater adaptation during stressful situations in elite athletes. PMID- 26379523 TI - Do intuitive and deliberate judgments rely on two distinct neural systems? A case study in face processing. AB - Arguably the most influential models of human decision-making today are based on the assumption that two separable systems - intuition and deliberation - underlie the judgments that people make. Our recent work is among the first to present neural evidence contrary to the predictions of these dual-systems accounts. We measured brain activations using functional magnetic resonance imaging while participants were specifically instructed to either intuitively or deliberately judge the authenticity of emotional facial expressions. Results from three different analyses revealed both common brain networks of activation across decision mode and differential activations as a function of strategy adherence. We take our results to contradict popular dual-systems accounts that propose a clear-cut dichotomy of the processing systems, and to support rather a unified model. According to this, intuitive and deliberate judgment processes rely on the same rules, though only the former are thought to be characterized by non conscious processing. PMID- 26379522 TI - The sensory-motor theory of rhythm and beat induction 20 years on: a new synthesis and future perspectives. AB - Some 20 years ago Todd and colleagues proposed that rhythm perception is mediated by the conjunction of a sensory representation of the auditory input and a motor representation of the body (Todd, 1994a, 1995), and that a sense of motion from sound is mediated by the vestibular system (Todd, 1992a, 1993b). These ideas were developed into a sensory-motor theory of rhythm and beat induction (Todd et al., 1999). A neurological substrate was proposed which might form the biological basis of the theory (Todd et al., 2002). The theory was implemented as a computational model and a number of experiments conducted to test it. In the following time there have been several key developments. One is the demonstration that the vestibular system is primal to rhythm perception, and in related work several experiments have provided further evidence that rhythm perception is body dependent. Another is independent advances in imaging, which have revealed the brain areas associated with both vestibular processing and rhythm perception. A third is the finding that vestibular receptors contribute to auditory evoked potentials (Todd et al., 2014a,b). These behavioral and neurobiological developments demand a theoretical overview which could provide a new synthesis over the domain of rhythm perception. In this paper we suggest four propositions as the basis for such a synthesis. (1) Rhythm perception is a form of vestibular perception; (2) Rhythm perception evokes both external and internal guidance of somatotopic representations; (3) A link from the limbic system to the internal guidance pathway mediates the "dance habit"; (4) The vestibular reward mechanism is innate. The new synthesis provides an explanation for a number of phenomena not often considered by rhythm researchers. We discuss these along with possible computational implementations and alternative models and propose a number of new directions for future research. PMID- 26379524 TI - A reinforcement learning approach to gait training improves retention. AB - Many gait training programs are based on supervised learning principles: an individual is guided towards a desired gait pattern with directional error feedback. While this results in rapid adaptation, improvements quickly disappear. This study tested the hypothesis that a reinforcement learning approach improves retention and transfer of a new gait pattern. The results of a pilot study and larger experiment are presented. Healthy subjects were randomly assigned to either a supervised group, who received explicit instructions and directional error feedback while they learned a new gait pattern on a treadmill, or a reinforcement group, who was only shown whether they were close to or far from the desired gait. Subjects practiced for 10 min, followed by immediate and overnight retention and over-ground transfer tests. The pilot study showed that subjects could learn a new gait pattern under a reinforcement learning paradigm. The larger experiment, which had twice as many subjects (16 in each group) showed that the reinforcement group had better overnight retention than the supervised group (a 32% vs. 120% error increase, respectively), but there were no differences for over-ground transfer. These results suggest that encouraging participants to find rewarding actions through self-guided exploration is beneficial for retention. PMID- 26379525 TI - Normal Visual Acuity and Electrophysiological Contrast Gain in Adults with High Functioning Autism Spectrum Disorder. AB - A common neurodevelopmental disorder, autism spectrum disorder (ASD), is defined by specific patterns in social perception, social competence, communication, highly circumscribed interests, and a strong subjective need for behavioral routines. Furthermore, distinctive features of visual perception, such as markedly reduced eye contact and a tendency to focus more on small, visual items than on holistic perception, have long been recognized as typical ASD characteristics. Recent debate in the scientific community discusses whether the physiology of low-level visual perception might explain such higher visual abnormalities. While reports of this enhanced, "eagle-like" visual acuity contained methodological errors and could not be substantiated, several authors have reported alterations in even earlier stages of visual processing, such as contrast perception and motion perception at the occipital cortex level. Therefore, in this project, we have investigated the electrophysiology of very early visual processing by analyzing the pattern electroretinogram-based contrast gain, the background noise amplitude, and the psychophysical visual acuities of participants with high-functioning ASD and controls with equal education. Based on earlier findings, we hypothesized that alterations in early vision would be present in ASD participants. This study included 33 individuals with ASD (11 female) and 33 control individuals (12 female). The groups were matched in terms of age, gender, and education level. We found no evidence of altered electrophysiological retinal contrast processing or psychophysical measured visual acuities. There appears to be no evidence for abnormalities in retinal visual processing in ASD patients, at least with respect to contrast detection. PMID- 26379526 TI - Mindfulness is associated with intrinsic functional connectivity between default mode and salience networks. AB - Mindfulness is attention to present moment experience without judgment. Mindfulness practice is associated with brain activity in areas overlapping with the default mode, salience, and central executive networks (DMN, SN, CEN). We hypothesized that intrinsic functional connectivity (iFC; i.e., synchronized ongoing activity) across these networks is associated with mindfulness scores. After 2 weeks of daily 20 min attention to breath training, healthy participants were assessed by mindfulness questionnaires and resting-state functional MRI. Independent component analysis (ICA) of imaging data revealed networks of interest, whose activity time series defined inter-network intrinsic functional connectivity (inter-iFC) by temporal correlation. Inter-iFC between subnetworks of the DMN and SN-and inter-iFC between subnetworks of the SN and left CEN at trend-was correlated with mindfulness scores. Additional control analyses about visual networks' inter-iFC support the specificity of our findings. Results provide evidence that mindfulness is associated with iFC between DMN and SN. Data suggest that ongoing interactions among central intrinsic brain networks link with the ability to attend to current experience without judgment. PMID- 26379527 TI - Titles change the esthetic appreciations of paintings. AB - Esthetic experiences of artworks are influenced by contextualizing information such as titles. However, how titles contribute to positive esthetic experiences is still an open issue. Considering that fluency, as well as effortful elaborate processing, potentially influence esthetic experiences, we tested how three different title types-semantically matching (fluent), semantically non-matching (non-fluent), and an "untitled" condition (control)-affected experiences of abstract, semi-abstract, and representational art. While participants viewed title/artwork combinations we assessed facial electromygraphic (fEMG) recordings over M. corrugator supercilii and M. zygomaticus major muscle to capture subtle changes in emotional and cognitive processing, and asked for subjective liking and interest. Matching titles, but also the more effortful untitled condition, produced higher liking compared to non-fluently processed, non-matching titles especially in abstract art. These results were reflected in fEMG with stronger M. corrugator activations in the non-matching condition followed by the untitled condition. This implies high cognitive effort as well as negative emotions. Only in the matching condition, M. zygomaticus was more strongly activated indicating positive emotions due to fluency. Interest, however, was hardly affected. These results show that high levels of dis-fluency and cognitive effort reduce liking. However, fluency as well as moderate levels of effort contribute to more positive esthetic experiences. PMID- 26379528 TI - Higher cardiorespiratory fitness levels are associated with greater hippocampal volume in breast cancer survivors. AB - As breast cancer treatment is associated with declines in brain and cognitive health, it is important to identify strategies to enhance the cognitive vitality of cancer survivors. In particular, the hippocampus is known to play an important role in brain and memory declines following cancer treatment. The hippocampus is also known for its plasticity and positive association with cardiorespiratory fitness (CRF). The present study explores whether CRF may hold promise for lessening declines in brain and cognitive health of a sample of breast cancer survivors within 3 years of completion of primary cancer treatment. We explored the role of cardiovascular fitness in hippocampal structure in breast cancer survivors and non-cancer female controls, as well as performed a median split to compare differences in hippocampal volume in relatively higher fit and lower fit cancer survivors and non-cancer controls. Indeed, CRF and total hippocampal volume were positively correlated in the cancer survivors. In particular, higher fit breast cancer survivors had comparable hippocampal volumes to non-cancer control participants (Cohen's d = 0.13; p > 0.3), whereas lower fit breast cancer survivors showed significantly smaller hippocampal volumes compared to both lower fit and higher fit control participants (Cohen's d = 0.87, p < 0.05). These results are the first to identify that CRF may protect the brain health of breast cancer survivors within 3 years of treatment. The present study uniquely contributes to the field of cancer and cognition and emphasizes the importance of investigating how individual differences in CRF play a role in brain changes of breast cancer survivors. PMID- 26379529 TI - Maladaptive and adaptive emotion regulation through music: a behavioral and neuroimaging study of males and females. AB - Music therapists use guided affect regulation in the treatment of mood disorders. However, self-directed uses of music in affect regulation are not fully understood. Some uses of music may have negative effects on mental health, as can non-music regulation strategies, such as rumination. Psychological testing and functional magnetic resonance imaging (fMRI) were used explore music listening strategies in relation to mental health. Participants (n = 123) were assessed for depression, anxiety and Neuroticism, and uses of Music in Mood Regulation (MMR). Neural responses to music were measured in the medial prefrontal cortex (mPFC) in a subset of participants (n = 56). Discharge, using music to express negative emotions, related to increased anxiety and Neuroticism in all participants and particularly in males. Males high in Discharge showed decreased activity of mPFC during music listening compared with those using less Discharge. Females high in Diversion, using music to distract from negative emotions, showed more mPFC activity than females using less Diversion. These results suggest that the use of Discharge strategy can be associated with maladaptive patterns of emotional regulation, and may even have long-term negative effects on mental health. This finding has real-world applications in psychotherapy and particularly in clinical music therapy. PMID- 26379531 TI - Editorial: Habits: plasticity, learning and freedom. PMID- 26379530 TI - Alteration of Basal Ganglia and Right Frontoparietal Network in Early Drug-Naive Parkinson's Disease during Heat Pain Stimuli and Resting State. AB - BACKGROUND: The symptoms and pathogenesis of Parkinson's disease (PD) are complicated and an accurate diagnosis of PD is difficult, particularly in early stage. Because functional magnetic resonance imaging (fMRI) is non-invasive and is characterized by the integration of different brain areas in terms of functional connectivity (FC), fMRI has been widely used in PD research. Non-motor symptom (NMS) features are also frequently present in PD before the onset of classical motor symptoms with pain as the primary NMS. Considering that PD could affect the pain process at multiple levels, we hypothesized that pain is one of the earliest symptoms in PD and investigated whether FC of the pain network was disrupted in PD without pain. To better understand the pathogenesis of pain in PD, we combined resting state and pain-stimuli-induced task state fMRI to identify alterations in FC related to pain in PD. METHODS: Fourteen early drug naive PD without pain and 17 age- and sex-matched healthy controls (HC) participated in our testing task. We used independent component analysis to select seven functional networks related to PD and pain. We focused on abnormalities in FC and in functional network connectivity (FNC) in PD compared with HC during the task (51 degrees C heat pain stimuli) and at rest. RESULTS: Compared with HC, PD showed decreased FC in putamen within basal ganglia network (BGN) in task state and decreased FC in putamen of salience network (SN) and mid cingulate cortex of sensorimotor network in rest state. FNC between the BGN and the SN are reduced during both states in PD compared with HC. In addition, right frontoparietal network (RFPN), which is considered as a bridge between the SN and default-mode network, was significantly disturbed during the task. CONCLUSION: These findings suggest that BGN plays a role in the pathological mechanisms of pain underlying PD, and RFPN likely contributes greatly to harmonization between intrinsic brain activity and external stimuli. PMID- 26379532 TI - Adults with high social anhedonia have altered neural connectivity with ventral lateral prefrontal cortex when processing positive social signals. AB - Social anhedonia (SA) is a debilitating characteristic of schizophrenia, a common feature in individuals at psychosis-risk, and a vulnerability for developing schizophrenia-spectrum disorders. Prior work (Hooker et al., 2014) revealed neural deficits in the ventral lateral prefrontal cortex (VLPFC) when processing positive social cues in a community sample of people with high SA. Lower VLPFC neural activity was related to more severe self-reported schizophrenia-spectrum symptoms as well as the exacerbation of symptoms after social stress. In the current study, psycho-physiological interaction (PPI) analysis was applied to further investigate the neural mechanisms mediated by the VLPFC during emotion processing. PPI analysis revealed that, compared to low SA controls, participants with high SA exhibited reduced connectivity between the VLPFC and the motor cortex, the inferior parietal and the posterior temporal regions when viewing socially positive (relative to neutral) emotions. Across all participants, VLPFC connectivity correlated with behavioral and self-reported measures of attentional control, emotion management, and reward processing. Our results suggest that impairments to the VLPFC mediated neural circuitry underlie the cognitive and emotional deficits associated with social anhedonia, and may serve as neural targets for prevention and treatment of schizophrenia-spectrum disorders. PMID- 26379533 TI - Attention deficits revealed by passive auditory change detection for pure tones and lexical tones in ADHD children. AB - Inattention (IA) has been a major problem in children with attention deficit/hyperactivity disorder (ADHD), accounting for their behavioral and cognitive dysfunctions. However, there are at least three processing steps underlying attentional control for auditory change detection, namely pre attentive change detection, involuntary attention orienting, and attention reorienting for further evaluation. This study aimed to examine whether children with ADHD would show deficits in any of these subcomponents by using mismatch negativity (MMN), P3a, and late discriminative negativity (LDN) as event-related potential (ERP) markers, under the passive auditory oddball paradigm. Two types of stimuli-pure tones and Mandarin lexical tones-were used to examine if the deficits were general across linguistic and non-linguistic domains. Participants included 15 native Mandarin-speaking children with ADHD and 16 age-matched controls (across groups, age ranged between 6 and 15 years). Two passive auditory oddball paradigms (lexical tones and pure tones) were applied. The pure tone oddball paradigm included a standard stimulus (1000 Hz, 80%) and two deviant stimuli (1015 and 1090 Hz, 10% each). The Mandarin lexical tone oddball paradigm's standard stimulus was /yi3/ (80%) and two deviant stimuli were /yi1/ and /yi2/ (10% each). The results showed no MMN difference, but did show attenuated P3a and enhanced LDN to the large deviants for both pure and lexical tone changes in the ADHD group. Correlation analysis showed that children with higher ADHD tendency, as indexed by parents' and teachers' ratings on ADHD symptoms, showed less positive P3a amplitudes when responding to large lexical tone deviants. Thus, children with ADHD showed impaired auditory change detection for both pure tones and lexical tones in both involuntary attention switching, and attention reorienting for further evaluation. These ERP markers may therefore be used for the evaluation of anti-ADHD drugs that aim to alleviate these dysfunctions. PMID- 26379534 TI - Altered Functional Connectivity of Fusiform Gyrus in Subjects with Amnestic Mild Cognitive Impairment: A Resting-State fMRI Study. AB - Visual cognition such as face recognition requests a high degree of functional integration between distributed brain areas of a network. It has been reported that the fusiform gyrus (FG) is an important brain area involved in facial cognition; altered connectivity of FG to some other regions may lead to a deficit in visual cognition especially face recognition. However, whether functional connectivity between the FG and other brain areas changes remains unclear in the resting state in amnestic mild cognitive impairment (aMCI) subjects. Here, we employed a resting-state functional MRI (fMRI) to examine alterations in functional connectivity of left/right FG comparing aMCI patients with age-matched control subjects. Forty-eight aMCI and 38 control subjects from the Alzheimer's disease Neuroimaging Initiative were analyzed. We concentrated on the correlation between low frequency fMRI time courses in the FG and those in all other brain regions. Relative to the control group, we found some discrepant regions in the aMCI group which presented increased or decreased connectivity with the left/right FG including the left precuneus, left lingual gyrus, right thalamus, supramarginal gyrus, left supplementary motor area, left inferior temporal gyrus, and left parahippocampus. More importantly, we also obtained that both left and right FG have increased functional connections with the left middle occipital gyrus (MOG) and right anterior cingulate gyrus (ACC) in aMCI patients. That was not a coincidence and might imply that the MOG and ACC also play a critical role in visual cognition, especially face recognition. These findings in a large part supported our hypothesis and provided a new insight in understanding the important subtype of MCI. PMID- 26379535 TI - Personality disorder symptomatology is associated with anomalies in striatal and prefrontal morphology. AB - Personality disorder symptomatology (PD-Sx) can result in personal distress and impaired interpersonal functioning, even in the absence of a clinical diagnosis, and is frequently comorbid with psychiatric disorders such as substance use, mood, and anxiety disorders; however, they often remain untreated, and are not taken into account in clinical studies. To investigate brain morphological correlates of PD-Sx, we measured subcortical volume and shape, and cortical thickness/surface area, based on structural magnetic resonance images. We investigated 37 subjects who reported PD-Sx exceeding DSM-IV Axis-II screening thresholds, and 35 age, sex, and smoking status-matched control subjects. Subjects reporting PD-Sx were then grouped into symptom-based clusters: N = 20 into Cluster B (reporting Antisocial, Borderline, Histrionic, or Narcissistic PD Sx) and N = 28 into Cluster C (reporting Obsessive-Compulsive, Avoidant, or Dependent PD-Sx); N = 11 subjects reported PD-Sx from both clusters, and none reported Cluster A (Paranoid, Schizoid, or Schizotypal) PD-Sx. Compared to control, Cluster C PD-Sx was associated with greater striatal surface area localized to the caudate tail, smaller ventral striatum volumes, and greater cortical thickness in right prefrontal cortex. Both Cluster B and C PD-Sx groups also showed trends toward greater posterior caudate volumes and orbitofrontal surface area anomalies, but these findings did not survive correction for multiple comparisons. The results point to morphological abnormalities that could contribute to Cluster C PD-Sx. In addition, the observations parallel those in substance use disorders, pointing to the importance of considering PD-Sx when interpreting findings in often-comorbid psychiatric disorders. PMID- 26379536 TI - The time course and characteristics of procedural learning in schizophrenia patients and healthy individuals. AB - Patients with schizophrenia have deficits in some types of procedural learning. Several mechanisms contribute to this learning in healthy individuals, including statistical and sequence-learning. To find preserved and impaired learning mechanisms in schizophrenia, we studied the time course and characteristics of implicitly introduced sequence-learning (SRT task) in 15 schizophrenia patients (seven mild and eight severe) and nine healthy controls, in short sessions over multiple days (5-22). The data show speed gains of similar magnitude for all groups, but the groups differed in overall speed and in the characteristics of the learning. By analyzing the data according to its spatial-position and temporal-order components, we provide evidence for two types of learning that could differentiate the groups: while the learning of the slower, severe group was dominated by statistical learning, the control group moved from a fast learning phase of statistical-related performance to subsequence learning (chunking). Our findings oppose the naive assumption that a similar gain of speed reflects a similar learning process; they indicate that the slower performance reflects the activation of a different motor plan than does the faster performance; and demonstrate that statistical learning and subsequence learning are two successive stages in implicit sequence learning, with chunks inferred from prior statistical computations. Our results indicate that statistical learning is intact in patients with schizophrenia, but is slower to develop in the severe patients. We suggest that this slow learning rate and the associated slow performance contribute to their deficit in developing sequence-specific learning by setting a temporal constraint on developing higher order associations. PMID- 26379537 TI - A Mozart is not a Pavarotti: singers outperform instrumentalists on foreign accent imitation. AB - Recent findings have shown that people with higher musical aptitude were also better in oral language imitation tasks. However, whether singing capacity and instrument playing contribute differently to the imitation of speech has been ignored so far. Research has just recently started to understand that instrumentalists develop quite distinct skills when compared to vocalists. In the same vein the role of the vocal motor system in language acquisition processes has poorly been investigated as most investigations (neurobiological and behavioral) favor to examine speech perception. We set out to test whether the vocal motor system can influence an ability to learn, produce and perceive new languages by contrasting instrumentalists and vocalists. Therefore, we investigated 96 participants, 27 instrumentalists, 33 vocalists and 36 non musicians/non-singers. They were tested for their abilities to imitate foreign speech: unknown language (Hindi), second language (English) and their musical aptitude. Results revealed that both instrumentalists and vocalists have a higher ability to imitate unintelligible speech and foreign accents than non musicians/non-singers. Within the musician group, vocalists outperformed instrumentalists significantly. CONCLUSION: First, adaptive plasticity for speech imitation is not reliant on audition alone but also on vocal-motor induced processes. Second, vocal flexibility of singers goes together with higher speech imitation aptitude. Third, vocal motor training, as of singers, may speed up foreign language acquisition processes. PMID- 26379538 TI - Time resolution dependence of information measures for spiking neurons: scaling and universality. AB - The mutual information between stimulus and spike-train response is commonly used to monitor neural coding efficiency, but neuronal computation broadly conceived requires more refined and targeted information measures of input-output joint processes. A first step toward that larger goal is to develop information measures for individual output processes, including information generation (entropy rate), stored information (statistical complexity), predictable information (excess entropy), and active information accumulation (bound information rate). We calculate these for spike trains generated by a variety of noise-driven integrate-and-fire neurons as a function of time resolution and for alternating renewal processes. We show that their time-resolution dependence reveals coarse-grained structural properties of interspike interval statistics; e.g., tau-entropy rates that diverge less quickly than the firing rate indicated by interspike interval correlations. We also find evidence that the excess entropy and regularized statistical complexity of different types of integrate and-fire neurons are universal in the continuous-time limit in the sense that they do not depend on mechanism details. This suggests a surprising simplicity in the spike trains generated by these model neurons. Interestingly, neurons with gamma-distributed ISIs and neurons whose spike trains are alternating renewal processes do not fall into the same universality class. These results lead to two conclusions. First, the dependence of information measures on time resolution reveals mechanistic details about spike train generation. Second, information measures can be used as model selection tools for analyzing spike train processes. PMID- 26379539 TI - Identification of neural firing patterns, frequency and temporal coding mechanisms in individual aortic baroreceptors. AB - In rabbit depressor nerve fibers, an on-off firing pattern, period-1 firing, and integer multiple firing with quiescent state were observed as the static pressure level was increased. A bursting pattern with bursts at the systolic phase of blood pressure, continuous firing, and bursting with burst at diastolic phase and quiescent state at systolic phase were observed as the mean level of the dynamic blood pressure was increased. For both static and dynamic pressures, the firing frequency of the first two firing patterns increased and of the last firing pattern decreased due to the quiescent state. If the quiescent state is disregarded, the spike frequency becomes an increasing trend. The instantaneous spike frequency of the systolic phase bursting, continuous firing, and diastolic phase bursting can reflect the temporal process of the systolic phase, whole procedure, and diastolic phase of the dynamic blood pressure signal, respectively. With increasing the static current corresponding to pressure level, the deterministic Hodgkin-Huxley (HH) model manifests a process from a resting state first to period-1 firing via a subcritical Hopf bifurcation and then to a resting state via a supercritical Hopf bifurcation, and the firing frequency increases. The on-off firing and integer multiple firing were here identified as noise-induced firing patterns near the subcritical and supercritical Hopf bifurcation points, respectively, using the stochastic HH model. The systolic phase bursting and diastolic phase bursting were identified as pressure-induced firings near the subcritical and supercritical Hopf bifurcation points, respectively, using an HH model with a dynamic signal. The firing, spike frequency, and instantaneous spike frequency observed in the experiment were simulated and explained using HH models. The results illustrate the dynamics of different firing patterns and the frequency and temporal coding mechanisms of aortic baroreceptor. PMID- 26379541 TI - Corrigendum: Cortico-striatal spike-timing dependent plasticity after activation of subcortical pathways. PMID- 26379540 TI - A machine learning methodology for the selection and classification of spontaneous spinal cord dorsum potentials allows disclosure of structured (non random) changes in neuronal connectivity induced by nociceptive stimulation. AB - Previous studies aimed to disclose the functional organization of the neuronal networks involved in the generation of the spontaneous cord dorsum potentials (CDPs) generated in the lumbosacral spinal segments used predetermined templates to select specific classes of spontaneous CDPs. Since this procedure was time consuming and required continuous supervision, it was limited to the analysis of two specific types of CDPs (negative CDPs and negative positive CDPs), thus excluding potentials that may reflect activation of other neuronal networks of presumed functional relevance. We now present a novel procedure based in machine learning that allows the efficient and unbiased selection of a variety of spontaneous CDPs with different shapes and amplitudes. The reliability and performance of the present method is evaluated by analyzing the effects on the probabilities of generation of different classes of spontaneous CDPs induced by the intradermic injection of small amounts of capsaicin in the anesthetized cat, a procedure known to induce a state of central sensitization leading to allodynia and hyperalgesia. The results obtained with the selection method presently described allowed detection of spontaneous CDPs with specific shapes and amplitudes that are assumed to represent the activation of functionally coupled sets of dorsal horn neurones that acquire different, structured configurations in response to nociceptive stimuli. These changes are considered as responses tending to adequate transmission of sensory information to specific functional requirements as part of homeostatic adjustments. PMID- 26379542 TI - Changes in voiding behavior in a mouse model of Alzheimer's disease. AB - Besides cognitive decline and behavioral alteration, urinary incontinence often occurs in patients suffering from Alzheimer's disease (AD). To determine whether the transgenic mouse model of AD, APP/PS1 (APP(SL)/PS1(M146L)) mouse, shows alteration of the urinary bladder function and anxiety, as for patients with AD, we examined the urinary marking behavior in relation to affective behavior. At 18 months of age voiding behavior of APP/PS1 and wild type (WT) mice was assessed by using a modified filter paper assay in combination with video tracing, with the cage divided into a center and corner zones. Anxiety-related behavior and locomotion were respectively tested in an elevated zero maze (EZM) and an open field (OF). The APP/PS1 mice urinated more in the center zone than the WT mice. The total volume of markings was significantly lower in the APP/PS1 mice. In both groups, the average volume of a marking in the corner zone was larger than in the center zone. In the EZM, the APP/PS1 mice spent less time in the open arms of the arena, considered as anxiogenic zones, than the WT mice. During the OF task, the APP/PS1 mice covered a longer distance than the WT mice. These findings show that the APP/PS1 mice have a different voiding behavior compared to the WT mice, i.e., urinating with small volumes and voiding in the center of the cage, and suggest that increased locomotor activity and anxiety-related behaviors are factors in the change in voiding pattern in the APP/PS1 mouse. PMID- 26379543 TI - A population of Pax7-expressing muscle progenitor cells show differential responses to muscle injury dependent on developmental stage and injury extent. AB - Skeletal muscle regeneration in vertebrates occurs by the activation of quiescent progenitor cells that express pax7 to repair and replace damaged myofibers. We have developed a mechanical injury paradigm in zebrafish to determine whether developmental stage and injury size affect the regeneration dynamics of skeletal muscle. We found that both small focal injuries, and large injuries affecting the entire myotome, lead to expression of myf5 and myogenin, which was prolonged in older larvae, indicating a slower process of regeneration. We characterized the endogenous behavior of a population of muscle-resident Pax7-expressing cells using a pax7a:eGFP transgenic line and found that GFP+ cell migration in the myotome dramatically declined between 5 and 7 days post-fertilization (dpf). Following a small single myotome injury, GFP+ cells responded by extending processes, before migrating to the injured myofibers. Furthermore, these cells responded more rapidly to injury in 4 dpf larvae compared to 7 dpf. Interestingly, we did not see GFP+ myofibers after repair of small injuries, indicating that pax7a-expressing cells did not contribute to myofiber formation in this injury context. On the contrary, numerous GFP+ myofibers could be observed after an extensive single myotome injury. Both injury models were accompanied by an increased number of proliferating GFP+ cells, which was more pronounced in larvae injured at 4 dpf than 7 dpf. This indicates intriguing developmental differences, at these early ages. Our data also suggests an interesting disparity in the role that pax7a-expressing muscle progenitor cells play during skeletal muscle regeneration, which may reflect the extent of muscle damage. PMID- 26379545 TI - Overestimating the Effects of Healthy Aging. PMID- 26379544 TI - The impacts of a GO-game (Chinese chess) intervention on Alzheimer disease in a Northeast Chinese population. AB - A GO game can enhance mental health, but its effects on Alzheimer Disease (AD) remains unknown. To address the issue, 147 AD patients were randomly assigned into control (without GO-game intervention), Short-time GO-Game Intervention (SGGI, 1 h daily) and Long-time GO-game Intervention (LGGI, 2 h daily) groups. After 6-month follow-up, the game reduced the mean score of Montgomery-Asberg Depression Rating Scales (MADRS) of 4.72 (95% CI, 0.69 to 9.12) and Hospital Anxiety and Depression Scale (HADS) of 1.75 (95% CI, 0.17-3.68), and increased the mean score of Global Assessment of Functioning (GAF) of 4.95 (95% CI, -1.37 9.18) and RAND-36 of 4.61 (95% CI, -2.75-11.32) (P < 0.05 via controls). A GO game intervention improved 9 of 11 items of KICA-dep (Kimberley Indigenous Cognitive Assessment of Depression). Meanwhile, serum levels of brain derived neurotrophic factor (BDNF) were higher in SGGI and LGGI groups (24.02 +/- 7.16 and 28.88 +/- 4.12 ng/ml respectively, P = 0.051) than those in controls (17.28 +/- 7.75 ng/ml) (P < 0.001). The serum levels of BDNF showed a negative relation with MADRS and a positive relation with RAND-36 (P < 0.01). A GO-game intervention ameliorates AD manifestations by up-regulating BDNF levels. PMID- 26379546 TI - Measuring physical activity in older adults: calibrating cut-points for the MotionWatch 8((c)). AB - Given the world's aging population, the staggering economic impact of dementia, the lack of effective treatments, and the fact a cure for dementia is likely many years away - there is an urgent need to develop interventions to prevent or at least delay dementia's progression. Thus, lifestyle approaches to promote healthy aging are an important line of scientific inquiry. Good sleep quality and physical activity (PA) are pillars of healthy aging, and as such, are an increasing focus for intervention studies aimed at promoting health and cognitive function in older adults. However, PA and sleep quality are difficult constructs to evaluate empirically. Wrist-worn actigraphy (WWA) is currently accepted as a valid objective measure of sleep quality. The MotionWatch 8((c)) (MW8) is the latest WWA, replacing the discontinued Actiwatch 4 and Actiwatch 7. In the current study, concurrent measurement of WWA and indirect calorimetry was performed during 10 different activities of daily living for 23 healthy older adults (aged 57-80 years) to determine cut-points for sedentary and moderate vigorous PA - using receiver operating characteristic curves - with the cut-point for light activity being the boundaries between sedentary and moderate to vigorous PA. In addition, simultaneous multi-unit reliability was determined for the MW8 using inter-class correlations. The current study is the first to validate MW8 activity count cut-points - for sedentary, light, and moderate to vigorous PA - specifically for use with healthy older adults. These cut-points provide important context for better interpretation of MW8 activity counts, and a greater understanding of what these counts mean in terms of PA. Hence, our results validate another level of analysis for researchers using the MW8 in studies aiming to examine PA and sleep quality concurrently in older adults. PMID- 26379547 TI - Aberrant Brain Network Efficiency in Parkinson's Disease Patients with Tremor: A Multi-Modality Study. AB - The coordination of spontaneous brain activity is widely enhanced relative to compensation activity in Parkinson's disease (PD) with tremor; however, the associated topological organization remains unclear. This study collected magnetic resonance imaging data from 36 participants [i.e., 16 PD patients and 20 matched normal controls (NCs)] and constructed wavelet-based functional and morphological brain networks for individual participants. Graph-based network analysis indicated that the information translation efficiency in the functional brain network was disrupted within the wavelet scale 2 (i.e., 0.063-0.125 Hz) in PD patients. Compared with the NCs, the network local efficiency was decreased and the network global efficiency was increased in PD patients. Network local efficiency could effectively discriminate PD patients from the NCs using multivariate pattern analysis, and could also describe the variability of tremor based on a multiple linear regression model (MLRM). However, these observations were not identified in the network global efficiency. Notably, the global and local efficiency were both significantly increased in the morphological brain network of PD patients. We further found that the global and local network efficiency both worked well on PD classifications (i.e., using MVPA) and clinical performance descriptions (i.e., using MLRM). More importantly, functional and morphological brain networks were highly associated in terms of network local efficiency in PD patients. This study sheds lights on network disorganization in PD with tremor and helps for understanding the neural basis underlying this type of PD. PMID- 26379548 TI - Imaging alterations of cardiomyocyte cAMP microdomains in disease. AB - 3',5'-cyclic adenosine monophosphate (cAMP) is an important second messenger which regulates heart function by acting in distinct subcellular microdomains. Recent years have provided deeper mechanistic insights into compartmentalized cAMP signaling and its link to cardiac disease. In this mini review, we summarize newest developments in this field achieved by cutting-edge biochemical and biophysical techniques. We further compile the data from different studies into a bigger picture of so far uncovered alterations in cardiomyocyte cAMP microdomains which occur in compensated cardiac hypertrophy and chronic heart failure. Finally, future research directions and translational perspectives are briefly discussed. PMID- 26379549 TI - Editorial: Improving the safety of cell therapy products by suicide gene transfer. PMID- 26379550 TI - Traditional Japanese herbal medicines for treatment of odontopathy. AB - This article highlights several refractory oral diseases, such as stomatitis, burning mouth syndrome (BMS), glossalgia, atypical facial pain (AFP), oral cancer, dry mouth, and Sjogren's syndrome (SJS), in which use of Japanese herbal medicines, Kampo medicines (KM), on the basis of Kampo theory could exert the maximum effects on human body. (1) In acute stomatitis, heat because of agitated vital energy may affect the head, chest, and middle abdominal region. Stomatitis is also related to the generation of reactive oxygen species (ROS). There are many antioxidants in the crude extracts of KM. Thus, we can control environmental factors (cold, heat, dampness, dryness) and vital energy, blood, and fluid of the organ systemically using KM to treat stomatitis and eliminate local ROS accumulation. (2) BMS, glossalgia, and AFP are multifactorial syndromes involving the interaction of biological and psychological factors. Local temperature decrease and edema often occur in chronic pain. These are local circulatory disturbances that can be resolved by improving the flow of blood and fluid. Several KM, such as Tokishakuyakusan and Kamishoyosan (KSS), are effective for enhancing peripheral circulation. Those such as Saikokaryukotuboreito, Yokukansan, KSS, and Saibokutou can reduce stress and associated pain by altering glutamatergic and monoaminergic transmission in the brain. The clinical efficacy of KM for BMS and AFP may depend on the regulation of the mesolimbic dopaminergic and descending glutamatergic pain modulation systems. (3) Regarding oral cancer treatment, I introduce four possible applications of KM, inhibition of the proliferation of cancer cells, complementation of the main cancer therapy, reduction of side effect caused by the main anti-cancer therapy and improvement of quality of life such as the overall status and/or oral discomfort. This review explains in more details Hozai such as Hochuekkito (HET), Juzendaihoto, and Ninjinyoeito (NYT) that are frequently used to improve both immunosuppression and deficiencies of Ki, Ketsu, and Sui in oral cancer patients. (4) Heat- and cold dryness stages exist in dry mouth and SJS. Byakkokaninjinto is useful for heat dryness, while NYT, Bakumondoto, and HET have moisturizing effects in the cold dryness stage. Thus, Kampo therapy is useful for many oral diseases that cannot be cured by western medicine. PMID- 26379551 TI - Regulation of CaMKII signaling in cardiovascular disease. AB - Heart failure (HF) is a major cause of death in the developed countries (Murray and Lopez, 1996; Koitabashi and Kass, 2012). Adverse cardiac remodeling that precedes heart muscle dysfunction is characterized by a myriad of molecular changes affecting the cardiomyocyte. Among these, alterations in protein kinase pathways play often an important mediator role since they link upstream pathologic stress signaling with downstream regulatory programs and thus affect both the structural and functional integrity of the heart muscle. In the context of cardiac disease, a profound understanding for the overriding mechanisms that regulate protein kinase activity (protein-protein interactions, post translational modifications, or targeting via anchoring proteins) is crucial for the development of specific and effective pharmacological treatment strategies targeting the failing myocardium. In this review, we focus on several mechanisms of upstream regulation of Ca(2+)-calmodulin-dependent protein kinase II that play a relevant pathophysiological role in the development and progression of cardiovascular disease; precise targeting of these mechanisms might therefore represent novel and promising tools for prevention and treatment of HF. PMID- 26379554 TI - Functional aortic stiffness: role of CD4(+) T lymphocytes. AB - The immune system is suggested to be essential in vascular remodeling and stiffening. To study the dependence upon lymphocytes in vascular stiffening, we compared an angiotensin II-model of vascular stiffening in normal C57BL/6J mice with lymphocyte-deficient RAG 1(-/-) mice and additionally characterized the component of vascular stiffness due to vasoconstriction vs. vascular remodeling. Chronic angiotensin II increased aortic pulse wave velocity, effective wall stiffness, and effective Young's modulus in C57BL/6J mice by three-fold but caused no change in the RAG 1(-/-) mice. These functional measurements were supported by aortic morphometric analysis. Adoptive transfer of CD4(+) T helper lymphocytes restored the angiotensin II-mediated aortic stiffening in the RAG 1( /-) mice. In order to account for the hydraulic vs. material effects of angiotensin II on pulse wave velocity, subcutaneous osmotic pumps were removed after 21 days of angiotensin II-infusion in the WT mice to achieve normotensive values. The pulse wave velocity (PWV) decreased from three- to two-fold above baseline values up to 7 days following pump removal. This study supports the pivotal role of the CD4(+) T-lymphocytes in angiotensin II-mediated vascular stiffening and that angiotensin II-mediated aortic stiffening is due to the additive effect of active vascular smooth muscle vasoconstriction and vascular remodeling. PMID- 26379555 TI - Commentary: Echolocation and vision complement each other in two bat species. PMID- 26379552 TI - Computational drug repositioning for peripheral arterial disease: prediction of anti-inflammatory and pro-angiogenic therapeutics. AB - Peripheral arterial disease (PAD) results from atherosclerosis that leads to blocked arteries and reduced blood flow, most commonly in the arteries of the legs. PAD clinical trials to induce angiogenesis to improve blood flow conducted in the last decade have not succeeded. We have recently constructed PADPIN, protein-protein interaction network (PIN) of PAD, and here we combine it with the drug-target relations to identify potential drug targets for PAD. Specifically, the proteins in the PADPIN were classified as belonging to the angiome, immunome, and arteriome, characterizing the processes of angiogenesis, immune response/inflammation, and arteriogenesis, respectively. Using the network-based approach we predict the candidate drugs for repositioning that have potential applications to PAD. By compiling the drug information in two drug databases DrugBank and PharmGKB, we predict FDA-approved drugs whose targets are the proteins annotated as anti-angiogenic and pro-inflammatory, respectively. Examples of pro-angiogenic drugs are carvedilol and urokinase. Examples of anti inflammatory drugs are ACE inhibitors and maraviroc. This is the first computational drug repositioning study for PAD. PMID- 26379553 TI - Does the sympathetic nervous system contribute to the pathophysiology of metabolic syndrome? AB - The metabolic syndrome (MS), formally known as syndrome X, is a clustering of several risk factors such as obesity, hypertension, insulin resistance, and dislypidemia which could lead to the development of diabetes and cardiovascular diseases (CVD). The frequent changes in the definition and diagnostic criteria of MS are indications of the controversy and the challenges surrounding the understanding of this syndrome among researchers. Obesity and insulin resistance are leading risk factors of MS. Moreover, obesity and hypertension are closely associated to the increase and aggravation of oxidative stress. The recommended treatment of MS frequently involves change of lifestyles to prevent weight gain. MS is not only an important screening tool for the identification of individuals at high risk of CVD and diabetes but also an indicator of suitable treatment. As sympathetic disturbances and oxidative stress are often associated with obesity and hypertension, the present review summarizes the role of sympathetic nervous system and oxidative stress in the MS. PMID- 26379556 TI - Knock-in mice harboring a Ca(2+) desensitizing mutation in cardiac troponin C develop early onset dilated cardiomyopathy. AB - The physiological consequences of aberrant Ca(2+) binding and exchange with cardiac myofilaments are not clearly understood. In order to examine the effect of decreasing Ca(2+) sensitivity of cTnC on cardiac function, we generated knock in mice carrying a D73N mutation (not known to be associated with heart disease in human patients) in cTnC. The D73N mutation was engineered into the regulatory N-domain of cTnC in order to reduce Ca(2+) sensitivity of reconstituted thin filaments by increasing the rate of Ca(2+) dissociation. In addition, the D73N mutation drastically blunted the extent of Ca(2+) desensitization of reconstituted thin filaments induced by cTnI pseudo-phosphorylation. Compared to wild-type mice, heterozygous knock-in mice carrying the D73N mutation exhibited a substantially decreased Ca(2+) sensitivity of force development in skinned ventricular trabeculae. Kaplan-Meier survival analysis revealed that median survival time for knock-in mice was 12 weeks. Echocardiographic analysis revealed that knock-in mice exhibited increased left ventricular dimensions with thinner walls. Echocardiographic analysis also revealed that measures of systolic function, such as ejection fraction (EF) and fractional shortening (FS), were dramatically reduced in knock-in mice. In addition, knock-in mice displayed electrophysiological abnormalities, namely prolonged QRS and QT intervals. Furthermore, ventricular myocytes isolated from knock-in mice did not respond to beta-adrenergic stimulation. Thus, knock-in mice developed pathological features similar to those observed in human patients with dilated cardiomyopathy (DCM). In conclusion, our results suggest that decreasing Ca(2+) sensitivity of the regulatory N-domain of cTnC is sufficient to trigger the development of DCM. PMID- 26379557 TI - The new nitric oxide donor cyclohexane nitrate induces vasorelaxation, hypotension, and antihypertensive effects via NO/cGMP/PKG pathway. AB - We investigated the cardiovascular effects induced by the nitric oxide donor Cyclohexane Nitrate (HEX). Vasodilatation, NO release and the effects of acute or sub-chronic treatment with HEX on cardiovascular parameters were evaluated. HEX induced endothelium-independent vasodilatation (Maximum effect [efficacy, ME] = 100.4 +/- 4.1%; potency [pD2] = 5.1 +/- 0.1). Relaxation was attenuated by scavenging nitric oxide (ME = 44.9 +/- 9.4% vs. 100.4 +/- 4.1%) or by inhibiting the soluble guanylyl cyclase (ME = 38.5 +/- 9.7% vs. 100.4 +/- 4.1%). In addition, pD2 was decreased after non-selective blockade of K(+) channels (pD2 = 3.6 +/- 0.1 vs. 5.1 +/- 0.1) or by inhibiting KATP channels (pD2 = 4.3 +/- 0.1 vs. 5.1 +/- 0.1). HEX increased NO levels in mesenteric arteries (33.2 +/- 2.3 vs. 10.7 +/- 0.2 au, p < 0.0001). Intravenous acute administration of HEX (1-20 mg/kg) induced hypotension and bradycardia in normotensive and hypertensive rats. Furthermore, starting at 6 weeks after the induction of 2K1C hypertension, oral treatment with the HEX (10 mg/Kg/day) for 7 days reduced blood pressure in hypertensive animals (134 +/- 6 vs. 170 +/- 4 mmHg, respectively). Our data demonstrate that HEX is a NO donor able to produce vasodilatation via NO/cGMP/PKG pathway and activation of the ATP-sensitive K(+) channels. Furthermore, HEX acutely reduces blood pressure and heart rate as well as produces antihypertensive effect in renovascular hypertensive rats. PMID- 26379558 TI - The Role of Prospection in Steep Temporal Reward Discounting in Gambling Addiction. AB - Addiction and pathological gambling (PG) have been consistently associated with high impulsivity and a steep devaluation of delayed rewards, a process that is known as temporal discounting (TD). Recent studies indicated that enhanced episodic future thinking (EFT) results in less impulsive TD in healthy controls (HCs). In a separate line of research, it has been suggested that non-linearities in time perception might contribute to reward devaluation during inter-temporal choice. Therefore, in addition to deficits in valuation processes and executive control, impairments in EFT and non-linearities in time perception have been hypothesized to contribute to steep TD in addiction. In this study, we explore such a potential association of impairments in EFT and time perception with steep TD in PG. We investigated 20 PGs and 20 matched HCs. TD was assessed via a standard computerized binary choice task. EFT was measured using a variation of the Autobiographical Memory Interview by Levine et al. (1). Time perception was assessed with a novel task, utilizing a non-linear rating procedure via circle size adjustments. Groups did not differ in baseline EFT. In both groups, a power law accounted time perception best, and the degree of non-linearity in time perception correlated with discounting across groups. A multiple regression analysis across all predictors and covariates revealed that only group status (PG/HC) and depression were significantly associated with discounting behavior such that PG increased TD and depression attenuated TD. Our findings speak against the idea that steep TD in PG is due to a skewed perception of time or impairments in EFT, at least under the present task conditions. The lack of overall group differences in EFT does not rule out the possibility of more complex interactions of EFT and decision-making. These interactions might be diminished in pathological gambling or addiction more generally, when other task configurations are used. PMID- 26379559 TI - Circadian Rhythms and Mood Disorders: Are the Phenomena and Mechanisms Causally Related? AB - This paper reviews some of the compelling evidence of disrupted circadian rhythms in individuals with mood disorders (major depressive disorder, seasonal affective disorder, and bipolar disorder) and that treatments such as bright light, designed to alter circadian rhythms, are effective in treating these disorders. Neurotransmitters in brain regions implicated in mood regulation exhibit circadian rhythms. A mouse model originally employed to identify a circadian gene has proven a potent model for mania. While this evidence is suggestive of an etiological role for altered circadian rhythms in mood disorders, it is compatible with other explanations, including that disrupted circadian rhythms and mood disorders are effects of a common cause and that genes and proteins implicated in both simply have pleiotropic effects. In light of this, the paper advances a proposal as to what evidence would be needed to establish a direct causal link between disruption of circadian rhythms and mood disorders. PMID- 26379560 TI - Non-Invasive Brain Stimulation for the Treatment of Symptoms Following Traumatic Brain Injury. AB - BACKGROUND: Traumatic brain injury (TBI) is a common cause of physical, psychological, and cognitive impairment, but many current treatments for TBI are ineffective or produce adverse side effects. Non-invasive methods of brain stimulation could help ameliorate some common trauma-induced symptoms. OBJECTIVE: This review summarizes instances in which repetitive Transcranial Magnetic Stimulation (rTMS) and transcranial Direct Current Stimulation (tDCS) have been used to treat symptoms following a TBI. A subsequent discussion attempts to determine the value of these methods in light of their potential risks. METHODS: The research databases of PubMed/MEDLINE and PsycINFO were electronically searched using terms relevant to the use of rTMS and tDCS as a tool to decrease symptoms in the context of rehabilitation post-TBI. RESULTS: Eight case-studies and four multi-subject reports using rTMS and six multi--subject studies using tDCS were found. Two instances of seizure are discussed. CONCLUSION: There is evidence that rTMS can be an effective treatment option for some post-TBI symptoms, such as depression, tinnitus, and neglect. Although the safety of this method remains uncertain, the use of rTMS in cases of mild TBI without obvious structural damage may be justified. Evidence on the effectiveness of tDCS is mixed, highlighting the need for additional investigations. PMID- 26379561 TI - mHealth App for Cannabis Users: Satisfaction and Perceived Usefulness. AB - OBJECTIVE: The aim of this study was to describe the characteristics of cannabis users and their levels of satisfaction with Stop-cannabis, an app intended for cannabis users who want to stop or reduce their cannabis use or prevent relapse. METHODS: A cross-sectional online survey was administered to users of Stop cannabis, a French-language app for iOS and Android devices. All app users were invited to participate in the survey via a message sent to the app. RESULTS: For hundred and eighty-two users answered the survey. The app was used daily by 348 of the participants (around 70%). More than 80% of participants (397) considered the app to have helped them "a little" or "a lot" to stop or reduce cannabis consumption. Most of the users' suggestions were related to the number or the quality of the messages sent by, or displayed in, the app. CONCLUSION: This pilot study supports the feasibility of such an app and its perceived usefulness. A self-selection bias, however, limits the conclusions of the study. The efficacy of the app should be evaluated in a randomized controlled trial. PMID- 26379562 TI - Acquisition of Chinese characters: the effects of character properties and individual differences among second language learners. AB - In light of the dramatic growth of Chinese learners worldwide and a need for cross-linguistic research on Chinese literacy development, this study drew upon theories of visual complexity effect (Su and Samuels, 2010) and dual-coding processing (Sadoski and Paivio, 2013) and investigated (a) the effects of character properties (i.e., visual complexity and radical presence) on character acquisition and (b) the relationship between individual learner differences in radical awareness and character acquisition. Participants included adolescent English-speaking beginning learners of Chinese in the U.S. Following Kuo et al. (2014), a novel character acquisition task was used to investigate the process of acquiring the meaning of new characters. Results showed that (a) characters with radicals and with less visual complexity were easier to acquire than characters without radicals and with greater visual complexity; and (b) individual differences in radical awareness were associated with the acquisition of all types of characters, but the association was more pronounced with the acquisition of characters with radicals. Theoretical and practical implications of the findings were discussed. PMID- 26379563 TI - Editorial: Frontiers in the acquisition of literacy. PMID- 26379565 TI - Action-projection in Japanese conversation: topic particles wa, mo, and tte for triggering categorization activities. AB - Conversation analytic work has revealed how anticipatory completions and preemptive actions can offer invaluable glimpses into the cognitive, contextual, grammatical, and temporal bases of projectability in turn-taking, by virtue of their potential not only as a display of participants' online prediction of roughly what it might take to complete a turn-in-progress but also to plan the next move. While the predicate-final word order and the incremental transformability of turns in Japanese generally lead to delayed projectability of turn-endings, this may be partially offset by the capacity of certain postpositional particles to trigger and propel prospective action trajectories. This article engages in a case study of the topic particle wa (and related particles mo and tte), by demonstrating how its grammatical affordances, the categorization activities, and cognitive processing it can set in motion, coupled with the immediate contextual, and temporal-productional features may coalesce to a point of critical mass, thereby enhancing the projectability of the not-yet produced trajectory of the current turn. The discussion attempts to contribute to recent debates on ways language-specific lexicogrammatical resources are deeply interlinked with the types of opportunities that are provided for social action. PMID- 26379564 TI - How might contact with nature promote human health? Promising mechanisms and a possible central pathway. AB - How might contact with nature promote human health? Myriad studies have linked the two; at this time the task of identifying the mechanisms underlying this link is paramount. This article offers: (1) a compilation of plausible pathways between nature and health; (2) criteria for identifying a possible central pathway; and (3) one promising candidate for a central pathway. The 21 pathways identified here include environmental factors, physiological and psychological states, and behaviors or conditions, each of which has been empirically tied to nature and has implications for specific physical and mental health outcomes. While each is likely to contribute to nature's impacts on health to some degree and under some circumstances, this paper explores the possibility of a central pathway by proposing criteria for identifying such a pathway and illustrating their use. A particular pathway is more likely to be central if it can account for the size of nature's impacts on health, account for nature's specific health outcomes, and subsume other pathways. By these criteria, enhanced immune functioning emerges as one promising candidate for a central pathway between nature and health. There may be others. PMID- 26379566 TI - The contribution of phonological knowledge, memory, and language background to reading comprehension in deaf populations. AB - While reading is challenging for many deaf individuals, some become proficient readers. Little is known about the component processes that support reading comprehension in these individuals. Speech-based phonological knowledge is one of the strongest predictors of reading comprehension in hearing individuals, yet its role in deaf readers is controversial. This could reflect the highly varied language backgrounds among deaf readers as well as the difficulty of disentangling the relative contribution of phonological versus orthographic knowledge of spoken language, in our case 'English,' in this population. Here we assessed the impact of language experience on reading comprehension in deaf readers by recruiting oral deaf individuals, who use spoken English as their primary mode of communication, and deaf native signers of American Sign Language. First, to address the contribution of spoken English phonological knowledge in deaf readers, we present novel tasks that evaluate phonological versus orthographic knowledge. Second, the impact of this knowledge, as well as memory measures that rely differentially on phonological (serial recall) and semantic (free recall) processing, on reading comprehension was evaluated. The best predictor of reading comprehension differed as a function of language experience, with free recall being a better predictor in deaf native signers than in oral deaf. In contrast, the measures of English phonological knowledge, independent of orthographic knowledge, best predicted reading comprehension in oral deaf individuals. These results suggest successful reading strategies differ across deaf readers as a function of their language experience, and highlight a possible alternative route to literacy in deaf native signers. HIGHLIGHTS: 1. Deaf individuals vary in their orthographic and phonological knowledge of English as a function of their language experience. 2. Reading comprehension was best predicted by different factors in oral deaf and deaf native signers. 3. Free recall memory (primacy effect) better predicted reading comprehension in deaf native signers as compared to oral deaf or hearing individuals. 4. Language experience should be taken into account when considering cognitive processes that mediate reading in deaf individuals. PMID- 26379568 TI - Temporal prediction errors modulate task-switching performance. AB - We have previously shown that temporal prediction errors (PEs, the differences between the expected and the actual stimulus' onset times) modulate the effective connectivity between the anterior cingulate cortex and the right anterior insular cortex (rAI), causing the activity of the rAI to decrease. The activity of the rAI is associated with efficient performance under uncertainty (e.g., changing a prepared behavior when a change demand is not expected), which leads to hypothesize that temporal PEs might disrupt behavior-change performance under uncertainty. This hypothesis has not been tested at a behavioral level. In this work, we evaluated this hypothesis within the context of task switching and concurrent temporal predictions. Our participants performed temporal predictions while observing one moving ball striking a stationary ball which bounced off with a variable temporal gap. Simultaneously, they performed a simple color comparison task. In some trials, a change signal made the participants change their behaviors. Performance accuracy decreased as a function of both the temporal PE and the delay. Explaining these results without appealing to ad hoc concepts such as "executive control" is a challenge for cognitive neuroscience. We provide a predictive coding explanation. We hypothesize that exteroceptive and proprioceptive minimization of PEs would converge in a fronto-basal ganglia network which would include the rAI. Both temporal gaps (or uncertainty) and temporal PEs would drive and modulate this network respectively. Whereas the temporal gaps would drive the activity of the rAI, the temporal PEs would modulate the endogenous excitatory connections of the fronto-striatal network. We conclude that in the context of perceptual uncertainty, the system is not able to minimize perceptual PE, causing the ongoing behavior to finalize and, in consequence, disrupting task switching. PMID- 26379567 TI - The language faculty that wasn't: a usage-based account of natural language recursion. AB - In the generative tradition, the language faculty has been shrinking-perhaps to include only the mechanism of recursion. This paper argues that even this view of the language faculty is too expansive. We first argue that a language faculty is difficult to reconcile with evolutionary considerations. We then focus on recursion as a detailed case study, arguing that our ability to process recursive structure does not rely on recursion as a property of the grammar, but instead emerges gradually by piggybacking on domain-general sequence learning abilities. Evidence from genetics, comparative work on non-human primates, and cognitive neuroscience suggests that humans have evolved complex sequence learning skills, which were subsequently pressed into service to accommodate language. Constraints on sequence learning therefore have played an important role in shaping the cultural evolution of linguistic structure, including our limited abilities for processing recursive structure. Finally, we re-evaluate some of the key considerations that have often been taken to require the postulation of a language faculty. PMID- 26379569 TI - Effects of visualizing statistical information - an empirical study on tree diagrams and 2 * 2 tables. AB - In their research articles, scholars often use 2 * 2 tables or tree diagrams including natural frequencies in order to illustrate Bayesian reasoning situations to their peers. Interestingly, the effect of these visualizations on participants' performance has not been tested empirically so far (apart from explicit training studies). In the present article, we report on an empirical study (3 * 2 * 2 design) in which we systematically vary visualization (no visualization vs. 2 * 2 table vs. tree diagram) and information format (probabilities vs. natural frequencies) for two contexts (medical vs. economical context; not a factor of interest). Each of N = 259 participants (students of age 16-18) had to solve two typical Bayesian reasoning tasks ("mammography problem" and "economics problem"). The hypothesis is that 2 * 2 tables and tree diagrams - especially when natural frequencies are included - can foster insight into the notoriously difficult structure of Bayesian reasoning situations. In contrast to many other visualizations (e.g., icon arrays, Euler diagrams), 2 * 2 tables and tree diagrams have the advantage that they can be constructed easily. The implications of our findings for teaching Bayesian reasoning will be discussed. PMID- 26379570 TI - Emotion word processing: does mood make a difference? AB - Visual emotion word processing has been in the focus of recent psycholinguistic research. In general, emotion words provoke differential responses in comparison to neutral words. However, words are typically processed within a context rather than in isolation. For instance, how does one's inner emotional state influence the comprehension of emotion words? To address this question, the current study examined lexical decision responses to emotionally positive, negative, and neutral words as a function of induced mood as well as their word frequency. Mood was manipulated by exposing participants to different types of music. Participants were randomly assigned to one of three conditions-no music, positive music, and negative music. Participants' moods were assessed during the experiment to confirm the mood induction manipulation. Reaction time results confirmed prior demonstrations of an interaction between a word's emotionality and its frequency. Results also showed a significant interaction between participant mood and word emotionality. However, the pattern of results was not consistent with mood-congruency effects. Although positive and negative mood facilitated responses overall in comparison to the control group, neither positive nor negative mood appeared to additionally facilitate responses to mood congruent words. Instead, the pattern of findings seemed to be the consequence of attentional effects arising from induced mood. Positive mood broadens attention to a global level, eliminating the category distinction of positive-negative valence but leaving the high-low arousal dimension intact. In contrast, negative mood narrows attention to a local level, enhancing within-category distinctions, in particular, for negative words, resulting in less effective facilitation. PMID- 26379571 TI - Investigating the relationship between interoceptive accuracy, interoceptive awareness, and emotional susceptibility. AB - Interoception, the sense of the physiological condition of the body, provides a basis for subjective feelings and emotions. Anterior insular cortex activity represents the state of the body and varies according to personality traits, such as emotional susceptibility (ES)-the tendency to experience feelings of discomfort and vulnerability when facing emotionally-laden stimuli. The accuracy of perceiving one's own bodily signals, or interoceptive accuracy (IAc), can be assessed with the heartbeat perception task (HPT), which is the experimental measure used by most of the existing research on interoception. However, IAc is only one facet of interoception. Interoceptive awareness (IAw) is the conscious perception of sensations from inside the body, such as heart beat, respiration, satiety, and the autonomic nervous system sensations related to emotions, which create the sense of the physiological condition of the body. We developed an Italian version of the recent self-report Multidimensional Assessment of Interoceptive Awareness (MAIA), tested its psychometric properties (reliability, dimensionality, and construct validity), and examined its relationship to ES, as assessed using the Emotional Susceptibility Scale, in a sample (n = 321) of healthy Italian psychology students (293 females, mean age: 20.5 years). In a subgroup of females (n = 135), we measured IAc with the HPT. We used a series of correlation/regression analyses to examine the complex interplay between the three constructs. We provide further evidence for a substantial independence of the IAc and IAw measures, confirming previous reports and current theoretical models that differentiate between IAc and IAw. Our analyses elucidate the complex relationship between distinct dimensions of IAw and ES, highlighting the need for continued efforts to shed more light on this topic. PMID- 26379572 TI - Are there right hemisphere contributions to visually-guided movement? Manipulating left hand reaction time advantages in dextrals. AB - Many studies have argued for distinct but complementary contributions from each hemisphere in the control of movements to visual targets. Investigators have attempted to extend observations from patients with unilateral left- and right hemisphere damage, to those using neurologically-intact participants, by assuming that each hand has privileged access to the contralateral hemisphere. Previous attempts to illustrate right hemispheric contributions to the control of aiming have focussed on increasing the spatial demands of an aiming task, to attenuate the typical right hand advantages, to try to enhance a left hand reaction time advantage in right-handed participants. These early attempts have not been successful. The present study circumnavigates some of the theoretical and methodological difficulties of some of the earlier experiments, by using three different tasks linked directly to specialized functions of the right hemisphere: bisecting, the gap effect, and visuospatial localization. None of these tasks were effective in reducing the magnitude of left hand reaction time advantages in right handers. Results are discussed in terms of alternatives to right hemispheric functional explanations of the effect, the one-dimensional nature of our target arrays, power and precision given the size of the left hand RT effect, and the utility of examining the proportions of participants who show these effects, rather than exclusive reliance on measures of central tendency and their associated null hypothesis significance tests. PMID- 26379574 TI - The influence of observers' sex on attention-demanding performance depends on performers' sex. AB - Post-error slowing (PES) indicates the slower responses after errors than after correct responses. Prior studies mainly focus on how the observation errors influence one own's performance, there is no study investigating how other's monitoring influence one own's performance. Additionally, the issue that whether social context influences the PES effect differently for females and males is still unclear. To address aforementioned issues, we required the participants to interact with a same-sex or opposite-sex partner to complete a color flanker task together (they sat next to each other, Experiment 1). One was the performer (perform the flanker task), and the other was the observer (monitor the error responses of performer). They alternated their roles in two successive blocks. To further verify the role of the interaction context, a control experiment was conducted in the individual context (Experiment 2). The results revealed that (1) larger PES effect was observed in females than in males in the interaction context; (2) the sex difference of PES effect mainly benefited from the opposite sex interaction; (3) larger PES effect was observed in the interaction context than in the individual context; (4) females' performance was influenced after an interaction with a same-sex or opposite-sex partner, whereas males' performance was merely influenced after an interaction with an opposite-sex partner. Taken together, these findings may suggest that (1) interaction context modulates the PES effect differently for females and males; (2) females are more susceptible to social information and hence more effective to adjust the post-error behaviors. PMID- 26379575 TI - Can lies be detected unconsciously? AB - People are typically poor at telling apart truthful and deceptive statements. Based on the Unconscious Thought Theory, it has been suggested that poor lie detection arises from the intrinsic limitations of conscious thinking and can be improved by facilitating the contribution of unconscious thought (UT). In support of this hypothesis, Reinhard et al. (2013) observed improved lie detection among participants engaging in UT. The present study aimed to replicate this UT advantage using a similar experimental procedure but with an important improvement in a key control condition. Specifically, participants judged the truthfulness of eight video recordings in three thinking modes: immediately after watching them or after a period of unconscious or conscious deliberation. Results from two experiments (combined N = 226) failed to reveal a significant difference in lie detection accuracy between the thinking modes, even after efforts were made to facilitate the occurrence of an UT advantage in Experiment 2. The results imply that the UT advantage in deception detection is not a robust phenomenon. PMID- 26379576 TI - Maternal depression and attachment: the evaluation of mother-child interactions during feeding practice. AB - Internal working models (IWMs) of attachment can moderate the effect of maternal depression on mother-child interactions and child development. Clinical depression pre-dating birthgiving has been found to predict incoherent and less sensitive caregiving. Dysfunctional patterns observed, included interactive modes linked to feeding behaviors which may interfere with hunger-satiation, biological rhythms, and the establishment of children's autonomy and individuation. Feeding interactions between depressed mothers and their children seem to be characterized by repetitive interactive failures: children refuse food through oppositional behavior or negativity. The aim of this study was to investigate parenting skills in the context of feeding in mothers with major depression from the point of view of attachment theory. This perspective emphasizes parents' emotion, relational and affective history and personal resources. The sample consisted of 60 mother-child dyads. Mothers were divided into two groups: 30 with Major Depression and 30 without disorders. Children's age ranged between 12 and 36 months The measures employed were the Adult Attachment Interview and the Scale for the Evaluation of Alimentary Interactions between Mothers and Children. Insecure attachment prevailed in mothers with major depression, with differences on the Subjective Experience and State of Mind Scales. Groups also differed in maternal sensitivity, degrees of interactive conflicts and negative affective states, all of which can hinder the development of adequate interactive patterns during feeding. The results suggest that IWMs can constitute an indicator for the evaluation of the relational quality of the dyad and that evaluations of dyadic interactions should be considered when programming interventions. PMID- 26379577 TI - Theory of mind in women with borderline personality disorder or schizophrenia: differences in overall ability and error patterns. AB - Although borderline personality disorder (BPD) and schizophrenia (SZ) are notably different mental disorders, they share problems in social cognition-or understanding the feelings, intentions and thoughts of other people. To date no studies have directly compared the social cognitive abilities of individuals with these two disorders. In this study, the social cognitive subdomain theory of mind was investigated in women with BPD (n = 25), women with SZ (n = 25) and healthy women (n = 25). An ecologically valid video-based measure (Movie for the Assessment of Social Cognition) was used. For the overall score, women with SZ performed markedly below both healthy women and women with BPD, whereas women with BPD did not perform significantly different compared to the healthy control group. A statistically significant error type * group interaction effect indicated that the groups differed with respect to kind of errors. Whereas women with BPD made mostly overmentalizing errors, women with SZ in addition committed undermentalizing errors. Our study suggests different magnitude and pattern of social cognitive problems in BPD and SZ. PMID- 26379573 TI - A unified 3D default space consciousness model combining neurological and physiological processes that underlie conscious experience. AB - The Global Workspace Theory and Information Integration Theory are two of the most currently accepted consciousness models; however, these models do not address many aspects of conscious experience. We compare these models to our previously proposed consciousness model in which the thalamus fills-in processed sensory information from corticothalamic feedback loops within a proposed 3D default space, resulting in the recreation of the internal and external worlds within the mind. This 3D default space is composed of all cells of the body, which communicate via gap junctions and electrical potentials to create this unified space. We use 3D illustrations to explain how both visual and non-visual sensory information may be filled-in within this dynamic space, creating a unified seamless conscious experience. This neural sensory memory space is likely generated by baseline neural oscillatory activity from the default mode network, other salient networks, brainstem, and reticular activating system. PMID- 26379578 TI - Neural basis of attachment-caregiving systems interaction: insights from neuroimaging studies. AB - The attachment and the caregiving system are complementary systems which are active simultaneously in infant and mother interactions. This ensures the infant survival and optimal social, emotional, and cognitive development. In this brief review we first define the characteristics of these two behavioral systems and the theory that links them, according to what Bowlby called the "attachment caregiving social bond" (Bowlby, 1969). We then follow with those neuroimaging studies that have focused on this particular issue, i.e., those which have studied the activation of the careging system in women (using infant stimuli) and have explored how the individual attachment model (through the Adult Attachment Interview) modulates its activity. Studies report altered activation in limbic and prefrontal areas and in basal ganglia and hypothalamus/pituitary regions. These altered activations are thought to be the neural substrate of the attachment-caregiving systems interaction. PMID- 26379579 TI - A general auditory bias for handling speaker variability in speech? Evidence in humans and songbirds. AB - Different speakers produce the same speech sound differently, yet listeners are still able to reliably identify the speech sound. How listeners can adjust their perception to compensate for speaker differences in speech, and whether these compensatory processes are unique only to humans, is still not fully understood. In this study we compare the ability of humans and zebra finches to categorize vowels despite speaker variation in speech in order to test the hypothesis that accommodating speaker and gender differences in isolated vowels can be achieved without prior experience with speaker-related variability. Using a behavioral Go/No-go task and identical stimuli, we compared Australian English adults' (naive to Dutch) and zebra finches' (naive to human speech) ability to categorize / I/ and /epsilon/ vowels of an novel Dutch speaker after learning to discriminate those vowels from only one other speaker. Experiments 1 and 2 presented vowels of two speakers interspersed or blocked, respectively. Results demonstrate that categorization of vowels is possible without prior exposure to speaker-related variability in speech for zebra finches, and in non-native vowel categories for humans. Therefore, this study is the first to provide evidence for what might be a species-shared auditory bias that may supersede speaker-related information during vowel categorization. It additionally provides behavioral evidence contradicting a prior hypothesis that accommodation of speaker differences is achieved via the use of formant ratios. Therefore, investigations of alternative accounts of vowel normalization that incorporate the possibility of an auditory bias for disregarding inter-speaker variability are warranted. PMID- 26379580 TI - Action dynamics reveal two types of cognitive flexibility in a homonym relatedness judgment task. AB - Cognitive flexibility is a central component of executive functions that allow us to behave meaningful in an ever changing environment. Here, we support a distinction between two different types of cognitive flexibility, shifting flexibility and spreading flexibility, based on independent underlying mechanisms commonly subsumed under the ability to shift cognitive sets. We use a homonym relatedness judgment task and combine it with mouse tracking to show that these two types of cognitive flexibility follow independent temporal patterns in their influence on participants' mouse movements during relatedness judgments. Our results are in concordance with the predictions of a neural field based framework that assumes the independence of the two types of flexibility. We propose that future studies about cognitive flexibility in the area of executive functions should take independent types into account, especially when studying moderators of cognitive flexibility. PMID- 26379581 TI - Iconicity in the lab: a review of behavioral, developmental, and neuroimaging research into sound-symbolism. AB - This review covers experimental approaches to sound-symbolism-from infants to adults, and from Sapir's foundational studies to twenty-first century product naming. It synthesizes recent behavioral, developmental, and neuroimaging work into a systematic overview of the cross-modal correspondences that underpin iconic links between form and meaning. It also identifies open questions and opportunities, showing how the future course of experimental iconicity research can benefit from an integrated interdisciplinary perspective. Combining insights from psychology and neuroscience with evidence from natural languages provides us with opportunities for the experimental investigation of the role of sound symbolism in language learning, language processing, and communication. The review finishes by describing how hypothesis-testing and model-building will help contribute to a cumulative science of sound-symbolism in human language. PMID- 26379582 TI - Family identification: a beneficial process for young adults who grow up in homes affected by parental intimate partner violence. AB - Exposure to parental intimate partner violence (parental IPV) is a complex trauma. Research within social psychology establishes that identification with social groups impacts positively on how we appraise, respond to and recover from traumatic events. IPV is also a highly stigmatized social phenomenon and social isolation is a major factor for families affected by IPV, yet strong identification with the family group may act as a beneficial psychological resource to young people who grew up in homes affected by IPV. The current study, an online survey of 355 students (M age = 20, 70% female), investigated if a psychosocial process, specifically identification with the family, may influence the relationship between the predictor, exposure to parental IPV, and outcomes, global self-esteem and state anxiety. Mediation analysis suggests that identification with the family has a positive influence on the relationship between exposure to parental IPV and psychological outcomes; exposure to parental IPV results in reduced family identification, but when family identification is strong it results in both reduced anxiety and increased self-esteem for young people. The findings highlight the importance of having a strong sense of belonging to the extended family for young people who were exposed to parental IPV, thus has implications for prevention, intervention, and social policy. PMID- 26379583 TI - Music and literature: are there shared empathy and predictive mechanisms underlying their affective impact? AB - It has been suggested that music and language had a shared evolutionary precursor before becoming mainly responsible for the communication of emotive and referential meaning respectively. However, emphasis on potential differences between music and language may discourage a consideration of the commonalities that music and literature share. Indeed, one possibility is that common mechanisms underlie their affective impact, and the current paper carefully reviews relevant neuroscientific findings to examine such a prospect. First and foremost, it will be demonstrated that considerable evidence of a common role of empathy and predictive processes now exists for the two domains. However, it will also be noted that an important open question remains: namely, whether the mechanisms underlying the subjective experience of uncertainty differ between the two domains with respect to recruitment of phylogenetically ancient emotion areas. It will be concluded that a comparative approach may not only help to reveal general mechanisms underlying our responses to music and literature, but may also help us better understand any idiosyncrasies in their capacity for affective impact. PMID- 26379584 TI - Do not play God: contrasting effects of deontological guilt and pride on decision making. AB - Recent accounts support the existence of two distinct feelings of guilt: altruistic guilt (AG), arising from the appraisal of not having been altruistic toward a victim and deontological guilt (DG), emerging from the appraisal of having violated an intuitive moral rule. Neuroimaging data has shown that the two guilt feelings trigger different neural networks, with DG selectively activating the insula, a brain area involved in the processing of disgust and self-reproach. Thus, insula activation could reflect the major involvement of self-reproach in DG rather than in AG. However, only a few studies have empirically tested whether and how DG and AG differently affect decision making and none have compared enhanced self-worth. Here we asked three groups of participants, respectively, induced with either pride, DG or AG, to participate in a third-party version of the ultimatum game in which they were asked to decide on behalf of others to accept or reject economic offers with several degrees of fairness. Results revealed that only deontological participants had higher median acceptances of Moderately Unfair offers as compared to proud participants. However fairness judgments were not different between groups, suggesting that deontological participants' moral standards had not decreased. Crucially, a higher increase in DG was associated with an increase in the odds of accepting 30:70 offers. The opposite effects that DG and pride exert on self-worth can account for these results. Specifically, proud participants felt entitled enough to take action in order to restore equity, while deontological participants followed the "Do not play God" principle, which limited their decisional autonomy, not allowing them to decide on behalf of others. PMID- 26379585 TI - Robot Comedy Lab: experimenting with the social dynamics of live performance. AB - The success of live comedy depends on a performer's ability to "work" an audience. Ethnographic studies suggest that this involves the co-ordinated use of subtle social signals such as body orientation, gesture, gaze by both performers and audience members. Robots provide a unique opportunity to test the effects of these signals experimentally. Using a life-size humanoid robot, programmed to perform a stand-up comedy routine, we manipulated the robot's patterns of gesture and gaze and examined their effects on the real-time responses of a live audience. The strength and type of responses were captured using SHORETMcomputer vision analytics. The results highlight the complex, reciprocal social dynamics of performer and audience behavior. People respond more positively when the robot looks at them, negatively when it looks away and performative gestures also contribute to different patterns of audience response. This demonstrates how the responses of individual audience members depend on the specific interaction they're having with the performer. This work provides insights into how to design more effective, more socially engaging forms of robot interaction that can be used in a variety of service contexts. PMID- 26379586 TI - Global-local visual processing impacts risk taking behaviors, but only at first. AB - We investigated the impact of early visual processing on decision-making during unpredictable, risky situations. Participants undertook Navon's (1977) task and attended to either global letters or local letters only, following which they completed the Balloon Analogue Risk Task (BART). It was observed that global focused individuals made more balloon pumps during the BART (i.e., took more risk), whereas local-focused individuals took less risk, albeit only initially. The theory of predictive and reactive control systems (PARCS) provides an excellent account of the data. Implications and future directions are discussed. PMID- 26379587 TI - Working memory load disrupts gaze-cued orienting of attention. AB - A large body of work has shown that a perceived gaze shift produces a shift in a viewer's spatial attention in the direction of the seen gaze. A controversial issue surrounds the extent to which this gaze-cued orienting effect is stimulus driven, or is under a degree of top-down control. In two experiments we show that the gaze-cued orienting effect is disrupted by a concurrent task that has been shown to place high demands on executive resources: random number generation (RNG). In Experiment 1 participants were faster to locate targets that appeared in gaze-cued locations relative to targets that appeared in locations opposite to those indicated by the gaze shifts, while simultaneously and continuously reciting aloud the digits 1-9 in order; however, this gaze-cueing effect was eliminated when participants continuously recited the same digits in a random order. RNG was also found to interfere with gaze-cued orienting in Experiment 2 where participants performed a speeded letter identification response. Together, these data suggest that gaze-cued orienting is actually under top-down control. We argue that top-down signals sustain a goal to shift attention in response to gazes, such that orienting ordinarily occurs when they are perceived; however, the goal cannot always be maintained when concurrent, multiple, competing goals are simultaneously active in working memory. PMID- 26379588 TI - A perfect storm: examining the synergistic effects of negative and positive emotional instability on promoting weight loss activities in anorexia nervosa. AB - Growing evidence indicates that both positive and negative emotion potentially influence the development and maintenance of anorexia nervosa, through both positive and negative reinforcement of weight loss activities. Such reactive emotional experience may be characterized by frequent and intense fluctuations in emotion, a construct known as "emotional instability." The purpose of this study was to investigate the association between positive emotional instability and weight loss activities in anorexia nervosa, and to investigate the synergistic effects of positive and negative emotional instability on promoting weight loss activities. Using ecological momentary assessment methods, 118 participants with anorexia nervosa reported their emotional experiences and behaviors at least six times daily over 2 weeks using a portable digital device. Using generalized linear modeling, results indicated that high levels of both positive and negative emotional instability, and the interaction between the two, were associated with more frequent weight-loss activities, beyond anorexia subtype and mean levels of emotional intensity. These findings indicate that when women with anorexia exhibit both high levels of both positive and negative emotional instability they are more prone to a variety of weight loss activities. The importance of addressing the role of both positive and negative emotion in anorexia treatment is discussed. PMID- 26379589 TI - The impact of anticipated stigma on psychological and physical health problems in the unemployed group. AB - Previous research has demonstrated that the unemployed suffer increased psychological and physical health problems compared to their employed counterparts. Further, unemployment leads to an unwanted new social identity that is stigmatizing, and stigma is known to be a stressor causing psychological and physical health problems. However, it is not yet known whether being stigmatized as an unemployed group member is associated with psychological and physical health in this group. The current study tested the impact of anticipated stigma (AS) on psychological distress (PD) and physical health problems, operationalized as somatic symptoms (SSs), in a volunteer sample of unemployed people. Results revealed that AS had a direct effect on both PD and SSs, such that greater AS significantly predicted higher levels of both. Moreover, the direct effect on SSs became non-significant when PD was taken into account. Thus, to the extent that unemployed participants anticipated experiencing greater stigma, they also reported increased PD, and this PD predicted increased SSs. Our findings complement and extend the existing literature on the relationships between stigmatized identities, PD and physical health problems, particularly in relation to the unemployed group. This group is important to consider both theoretically, given the unwanted and transient nature of the identity compared to other stigmatized identities, but also practically, as the findings indicate a need to orient to the perceived valence of the unemployed identity and its effects on psychological and physical health. PMID- 26379590 TI - Improving spatial-simultaneous working memory in Down syndrome: effect of a training program led by parents instead of an expert. AB - Recent studies have suggested that the visuospatial component of working memory (WM) is selectively impaired in individuals with Down syndrome (DS), the deficit relating specifically to the spatial-simultaneous component, which is involved when stimuli are presented simultaneously. The present study aimed to analyze the effects of a computer-based program for training the spatial-simultaneous component of WM in terms of: specific effects (on spatial-simultaneous WM tasks); near and far transfer effects (on spatial-sequential and visuospatial abilities, and everyday memory tasks); and maintenance effects (1 month after the training). A comparison was drawn between the results obtained when the training was led by parents at home as opposed to an expert in psychology. Thirty-nine children and adolescents with DS were allocated to one of two groups: the training was administered by an expert in one, and by appropriately instructed parents in the other. The training was administered individually twice a week for a month, in eight sessions lasting approximately 30 min each. Our participants' performance improved after the training, and these results were maintained a month later in both groups. Overall, our findings suggest that spatial-simultaneous WM performance can be improved, obtaining specific and transfer gains; above all, it seems that, with adequate support, parents could effectively administer a WM training to their child. PMID- 26379591 TI - Novel methodology to examine cognitive and experiential factors in language development: combining eye-tracking and LENA technology. AB - Developmental systems theory posits that development cannot be segmented by influences acting in isolation, but should be studied through a scientific lens that highlights the complex interactions between these forces over time (Overton, 2013a). This poses a unique challenge for developmental psychologists studying complex processes like language development. In this paper, we advocate for the combining of highly sophisticated data collection technologies in an effort to move toward a more systemic approach to studying language development. We investigate the efficiency and appropriateness of combining eye-tracking technology and the LENA (Language Environment Analysis) system, an automated language analysis tool, in an effort to explore the relation between language processing in early development, and external dynamic influences like parent and educator language input in the home and school environments. Eye-tracking allows us to study language processing via eye movement analysis; these eye movements have been linked to both conscious and unconscious cognitive processing, and thus provide one means of evaluating cognitive processes underlying language development that does not require the use of subjective parent reports or checklists. The LENA system, on the other hand, provides automated language output that describes a child's language-rich environment. In combination, these technologies provide critical information not only about a child's language processing abilities but also about the complexity of the child's language environment. Thus, when used in conjunction these technologies allow researchers to explore the nature of interacting systems involved in language development. PMID- 26379592 TI - Reading is for girls!? The negative impact of preschool teachers' traditional gender role attitudes on boys' reading related motivation and skills. AB - According to gender stereotypes, reading is for girls. In this study, we investigated the role of preschool teachers in transmitting such gendered expectations. We suggest that boys are less motivated to read in preschool, and less competent in reading 1 year later in primary school, if their preschool teacher holds a traditional gender role attitude than if the teacher has egalitarian beliefs. In 135 independent dyads of a female preschool teacher (N = 135) and one boy (n = 65) or one girl (n = 70) we measured teacher's gender role attitude, child's reading related motivation as well as precursors of reading skills in preschool, and child's reading skills at the end of first grade in primary school. As expected, the more traditional preschool teachers' gender role attitude was, the weaker was boys' motivation to (learn to) read while girls' motivation was unrelated to teachers' gender role attitude. In either gender, motivation in preschool predicted reading skills at the end of first grade. PMID- 26379593 TI - Commentary: Pre-crastination: hastening subgoal completion at the expense of extra physical effort. PMID- 26379594 TI - The quadratic relationship between difficulty of intelligence test items and their correlations with working memory. AB - Fluid intelligence (Gf) is a crucial cognitive ability that involves abstract reasoning in order to solve novel problems. Recent research demonstrated that Gf strongly depends on the individual effectiveness of working memory (WM). We investigated a popular claim that if the storage capacity underlay the WM-Gf correlation, then such a correlation should increase with an increasing number of items or rules (load) in a Gf-test. As often no such link is observed, on that basis the storage-capacity account is rejected, and alternative accounts of Gf (e.g., related to executive control or processing speed) are proposed. Using both analytical inference and numerical simulations, we demonstrated that the load dependent change in correlation is primarily a function of the amount of floor/ceiling effect for particular items. Thus, the item-wise WM correlation of a Gf-test depends on its overall difficulty, and the difficulty distribution across its items. When the early test items yield huge ceiling, but the late items do not approach floor, that correlation will increase throughout the test. If the early items locate themselves between ceiling and floor, but the late items approach floor, the respective correlation will decrease. For a hallmark Gf test, the Raven-test, whose items span from ceiling to floor, the quadratic relationship is expected, and it was shown empirically using a large sample and two types of WMC tasks. In consequence, no changes in correlation due to varying WM/Gf load, or lack of them, can yield an argument for or against any theory of WM/Gf. Moreover, as the mathematical properties of the correlation formula make it relatively immune to ceiling/floor effects for overall moderate correlations, only minor changes (if any) in the WM-Gf correlation should be expected for many psychological tests. PMID- 26379595 TI - Cascadedness in Chinese written word production. AB - In written word production, is activation transmitted from lexical-semantic selection to orthographic encoding in a serial or cascaded fashion? Very few previous studies have addressed this issue, and the existing evidence comes from languages with alphabetic orthographic systems. We report a study in which Chinese participants were presented with colored line drawings of objects and were instructed to write the name of the color while attempting to ignore the object. Significant priming was found when on a trial, the written response shared an orthographic radical with the written name of the object. This finding constitutes clear evidence that task-irrelevant lexical codes activate their corresponding orthographic representation, and hence suggests that activation flows in a cascaded fashion within the written production system. Additionally, the results speak to how the time interval between processing of target and distractor dimensions affects and modulates the emergence of orthographic facilitation effects. PMID- 26379596 TI - Self-compassion influences PTSD symptoms in the process of change in trauma focused cognitive-behavioral therapies: a study of within-person processes. AB - Although self-compassion is considered a promising change agent in the treatment of posttraumatic stress disorder (PTSD), no studies of this hypothesis exist. This study examined the within-person relationship of self-compassion components (self-kindness, common humanity, mindfulness, self-judgment, isolation, over identification) and subsequent PTSD symptoms over the course of therapy. METHOD: PTSD patients (n = 65) were randomized to either standard prolonged exposure, which includes imaginal exposure (IE) to the traumatic memory, or modified prolonged exposure, where imagery re-scripting (IR) of the memory replaced IE as the imagery component of prolonged exposure in a 10 weeks residential program. They were assessed weekly on self-compassion and PTSD symptom measures. The centering method of detrending was used to separate the variance related to the within-person process of change over the course of treatment from between-person variance. RESULTS: The self-compassion components self-kindness, self-judgment, isolation, and over-identification had a within-person effect on subsequent PTSD symptoms. These relationships were independent of therapy form. The within-person relationship between self-judgment and subsequent PTSD symptoms was stronger in patients with higher initial self-judgment. By contrast, there were few indications that within-person variations in PTSD symptoms predict subsequent self-compassion components. CONCLUSION: The results support the role of self compassion components in maintaining PTSD and imply the recommendation to facilitate decrease of self-judgment, isolation, and over-identification and increase of self-kindness in the treatment of PTSD patients. The reduction of self-judgment appears to be most important, especially for patients with a high initial level of self-judgment. PMID- 26379597 TI - The smell of death: evidence that putrescine elicits threat management mechanisms. AB - The ability to detect and respond to chemosensory threat cues in the environment plays a vital role in survival across species. However, little is known about which chemical compounds can act as olfactory threat signals in humans. We hypothesized that brief exposure to putrescine, a chemical compound produced by the breakdown of fatty acids in the decaying tissue of dead bodies, can function as a chemosensory warning signal, activating threat management responses (e.g., heightened alertness, fight-or-flight responses). This hypothesis was tested by gaging people's responses to conscious and non-conscious exposure to putrescine. In Experiment 1, putrescine increased vigilance, as measured by a reaction time task. In Experiments 2 and 3, brief exposure to putrescine (vs. ammonia and a scentless control condition) prompted participants to walk away faster from the exposure site. Experiment 3 also showed that putrescine elicited implicit cognitions related to escape and threat. Experiment 4 found that exposure to putrescine, presented here below the threshold of conscious awareness, increased hostility toward an out-group member. Together, the results are the first to indicate that humans can process putrescine as a warning signal that mobilizes protective responses to deal with relevant threats. The implications of these results are briefly discussed. PMID- 26379598 TI - Balancing emotional processing with ongoing cognitive activity: the effects of task modality on intrusions and rumination. AB - In the present paper we aimed to show that competition for resources between post emotional processes and the execution of a cognitive task will result in two possible effects: (1) an impairment of the cognitive task in the short run and (2) an elongation of intrusions and rumination in the long run. The outcome of this competition is influenced by the interaction of the modality (verbal vs. visuospatial) of cognitive tasks run in the aftermath of an emotional experience and the nature (verbal vs. visuospatial) of the same experience. Non-clinical participants were given a working memory task (OSPAN vs. an analog Visual task) before and after the presentation of negative vs. neutral material (a novel excerpt in Experiment 1 and a video clip in Experiment 2). Intrusions and rumination were measured after a 24-h delay. Rumination was also assessed immediately after the experimental induction. Results showed that exposure to verbal negative material impaired verbal performance (Experiment 1); by contrast, exposure to visual negative material impaired both verbal and visuospatial performance (Experiment 2). Intrusions were only affected by the emotional valence of the original experience, while performing a visuospatial task resulted in enhanced rumination only after exposure to verbal emotional material. The findings of both experiments suggest that emotional processing spreads over time in balance with ongoing cognitive activities, and, in such a balance, the visuospatial processing mode tends to prevail over verbal engagements. PMID- 26379599 TI - Emotional expressions of old faces are perceived as more positive and less negative than young faces in young adults. AB - Interpreting the emotions of others through their facial expressions can provide important social information, yet the way in which we judge an emotion is subject to psychosocial factors. We hypothesized that the age of a face would bias how the emotional expressions are judged, with older faces generally more likely to be viewed as having more positive and less negative expressions than younger faces. Using two-alternative forced-choice perceptual decision tasks, participants sorted young and old faces of which emotional expressions were gradually morphed into one of two categories-"neutral vs. happy" and "neutral vs. angry." The results indicated that old faces were more frequently perceived as having a happy expression at the lower emotional intensity levels, and less frequently perceived as having an angry expression at the higher emotional intensity levels than younger faces in young adults. Critically, the perceptual decision threshold at which old faces were judged as happy was lower than for young faces, and higher for angry old faces compared to young faces. These findings suggest that the age of the face influences how its emotional expression is interpreted in social interactions. PMID- 26379601 TI - A large receptive-expressive gap in bilingual children. AB - The present study focuses on the discrepancy between receptive and expressive language competence among bilingual children and tests possible explanatory factors of this gap. The sample consisted of 406 bilingual children with German as their second language (L2) and 46 different first languages. Receptive and expressive German language competence (L2) were measured with a standardized language development test at the age of 43 months. As expected, a significant gap in receptive and expressive German language competence (L2) emerged in all language groups. The size of the gap reached 1 SD and correlated with the amount of language contact and thus provides support for the language exposure hypothesis. However, we found no evidence for the language familiarity hypothesis. The present study contributes to the understanding of mechanisms in bilingual language development and, hence, is consequential for both basic research and language assessment practice. PMID- 26379600 TI - Reduction in ventral striatal activity when anticipating a reward in depression and schizophrenia: a replicated cross-diagnostic finding. AB - In the research domain framework (RDoC), dysfunctional reward expectation has been proposed to be a cross-diagnostic domain in psychiatry, which may contribute to symptoms common to various neuropsychiatric conditions, such as anhedonia or apathy/avolition. We used a modified version of the Monetary Incentive Delay (MID) paradigm to obtain functional MRI images from 22 patients with schizophrenia, 24 with depression and 21 controls. Anhedonia and other symptoms of depression, and overall positive and negative symptomatology were also measured. We hypothesized that the two clinical groups would have a reduced activity in the ventral striatum when anticipating reward (compared to anticipation of a neutral outcome) and that striatal activation would correlate with clinical measures of motivational problems and anhedonia. Results were consistent with the first hypothesis: two clusters in both the left and right ventral striatum were found to differ between the groups in reward anticipation. Post-hoc analysis showed that this was due to higher activation in the controls compared to the schizophrenia and the depression groups in the right ventral striatum, with activation differences between depression and controls also seen in the left ventral striatum. No differences were found between the two patient groups, and there were no areas of abnormal cortical activation in either group that survived correction for multiple comparisons. Reduced ventral striatal activity was related to greater anhedonia and overall depressive symptoms in the schizophrenia group, but not in the participants with depression. Findings are discussed in relation to previous literature but overall are supporting evidence of reward system dysfunction across the neuropsychiatric continuum, even if the specific clinical relevance is still not fully understood. We also discuss how the RDoC approach may help to solve some of the replication problems in psychiatric fMRI research. PMID- 26379603 TI - To make people save energy tell them what others do but also who they are: a preliminary study. AB - A way to make people save energy is by informing them that "comparable others" save more. We investigated whether, one can further improve this nudge by manipulating Who the "comparable others" are. We asked participants to imagine receiving feedback stating that their energy consumption exceeded that of "comparable others" by 10%. We varied Who the "comparable others" were in a 2 * 2 design: they were a household that was located either in the same neighborhood as themselves or in a different neighborhood, and its members were either identified (by names and a photograph) or unidentified. We also included two control conditions: one where no feedback was provided, and one where only statistical feedback was provided (feedback about an average household). We found that it matters Who the "comparable others" are. The most effective feedback was when the referent household was from the same neighborhood as the individual's and its members were not identified. PMID- 26379602 TI - Theory of mind in utterance interpretation: the case from clinical pragmatics. AB - The cognitive basis of utterance interpretation is an area that continues to provoke intense theoretical debate among pragmatists. That utterance interpretation involves some type of mind-reading or theory of mind (ToM) is indisputable. However, theorists are divided on the exact nature of this ToM based mechanism. In this paper, it is argued that the only type of ToM-based mechanism that can adequately represent the cognitive basis of utterance interpretation is one which reflects the rational, intentional, holistic character of interpretation. Such a ToM-based mechanism is supported on conceptual and empirical grounds. Empirical support for this view derives from the study of children and adults with pragmatic disorders. Specifically, three types of clinical case are considered. In the first case, evidence is advanced which indicates that individuals with pragmatic disorders exhibit deficits in reasoning and the use of inferences. These deficits compromise the ability of children and adults with pragmatic disorders to comply with the rational dimension of utterance interpretation. In the second case, evidence is presented which suggests that subjects with pragmatic disorders struggle with the intentional dimension of utterance interpretation. This dimension extends beyond the recognition of communicative intentions to include the attribution of a range of cognitive and affective mental states that play a role in utterance interpretation. In the third case, evidence is presented that children and adults with pragmatic disorders struggle with the holistic character of utterance interpretation. This serves to distort the contexts in which utterances are processed for their implicated meanings. The paper concludes with some thoughts about the role of theorizing in relation to utterance interpretation. PMID- 26379604 TI - The duality of temporal encoding - the intrinsic and extrinsic representation of time. AB - While time is well acknowledged for having a fundamental part in our perception, questions on how it is represented are still matters of great debate. One of the main issues in question is whether time is represented intrinsically at the neural level, or is it represented within dedicated brain regions. We used an fMRI block design to test if we can impose covert encoding of temporal features of faces and natural scenes stimuli within category selective neural populations by exposing subjects to four types of temporal variance, ranging from 0% up to 50% variance. We found a gradual increase in neural activation associated with the gradual increase in temporal variance within category selective areas. A second level analysis showed the same pattern of activations within known brain regions associated with time representation, such as the Cerebellum, the Caudate, and the Thalamus. We concluded that temporal features are integral to perception and are simultaneously represented within category selective regions and globally within dedicated regions. Our second conclusion, drown from our covert procedure, is that time encoding, at its basic level, is an automated process that does not require attention allocated toward the temporal features nor does it require dedicated resources. PMID- 26379607 TI - The meaning of significance in data testing. PMID- 26379606 TI - Counter-stereotypical pictures as a strategy for overcoming spontaneous gender stereotypes. AB - The present research investigated the use of counter-stereotypical pictures as a strategy for overcoming spontaneous gender stereotypes when certain social role nouns and professional terms are read. Across two experiments, participants completed a judgment task in which they were presented with word pairs comprised of a role noun with a stereotypical gender bias (e.g., beautician) and a kinship term with definitional gender (e.g., brother). Their task was to quickly decide whether or not both terms could refer to one person. In each experiment they completed two blocks of such judgment trials separated by a training session in which they were presented with pictures of people working in gender counter stereotypical (Experiment 1) or gender stereotypical roles (Experiment 2). To ensure participants were focused on the pictures, they were also required to answer four questions on each one relating to the character's leisure activities, earnings, job satisfaction, and personal life. Accuracy of judgments to stereotype incongruent pairings was found to improve significantly across blocks when participants were exposed to counter-stereotype images (9.87%) as opposed to stereotypical images (0.12%), while response times decreased significantly across blocks in both studies. It is concluded that exposure to counter-stereotypical pictures is a valuable strategy for overcoming spontaneous gender stereotype biases in the short term. PMID- 26379605 TI - The perception of speech modulation cues in lexical tones is guided by early language-specific experience. AB - A number of studies showed that infants reorganize their perception of speech sounds according to their native language categories during their first year of life. Still, information is lacking about the contribution of basic auditory mechanisms to this process. This study aimed to evaluate when native language experience starts to noticeably affect the perceptual processing of basic acoustic cues [i.e., frequency-modulation (FM) and amplitude-modulation information] known to be crucial for speech perception in adults. The discrimination of a lexical-tone contrast (rising versus low) was assessed in 6- and 10-month-old infants learning either French or Mandarin using a visual habituation paradigm. The lexical tones were presented in two conditions designed to either keep intact or to severely degrade the FM and fine spectral cues needed to accurately perceive voice-pitch trajectory. A third condition was designed to assess the discrimination of the same voice-pitch trajectories using click trains containing only the FM cues related to the fundamental-frequency (F0) in French- and Mandarin-learning 10-month-old infants. Results showed that the younger infants of both language groups and the Mandarin-learning 10-month-olds discriminated the intact lexical-tone contrast while French-learning 10-month olds failed. However, only the French 10-month-olds discriminated degraded lexical tones when FM, and thus voice-pitch cues were reduced. Moreover, Mandarin learning 10-month-olds were found to discriminate the pitch trajectories as presented in click trains better than French infants. Altogether, these results reveal that the perceptual reorganization occurring during the first year of life for lexical tones is coupled with changes in the auditory ability to use speech modulation cues. PMID- 26379608 TI - That's not funny! - But it should be: effects of humorous emotion regulation on emotional experience and memory. AB - Previous research has shown that humorous reappraisal can reduce elicited negative emotions, suggesting that humor may be a functional strategy to cope with emotionally negative situations. However, the effect of humorous reappraisal on later memory about the emotion-eliciting situation is currently unknown, although this is crucial for more adaptive responding in future situations. To address this issue, we examined the effects of humorous reappraisal on both emotional experience and memory, compared to non-humorous rational reappraisal and a non-reappraisal control condition. Replicating previous findings, humorous reappraisal reduced evoked negative valence and arousal levels very effectively, and the down-regulation of experienced negative emotions was even more pronounced after humorous compared to rational reappraisal. Regarding later memory for emotion-eliciting stimuli, both humorous and rational reappraisal reduced free recall, but recognition memory was unaffected, with memory strength being stronger after humorous than after rational reappraisal. These results indicate that humor seems to be indeed an optimal strategy to cope with negative situations because humor can help us to feel better when confronted with negative stimuli, but still allows us to retrieve stimulus information later when afforded to do so by the presence of appropriate contextual features. PMID- 26379610 TI - A reverse order interview does not aid deception detection regarding intentions. AB - Promising recent research suggests that more cognitively demanding interviews improve deception detection accuracy. Would these cognitively demanding techniques work in the same way when discriminating between true and false future intentions? In Experiment 1 participants planned to complete a task, but instead were intercepted and interviewed about their intentions. Participants lied or told the truth, and were subjected to high (reverse order) or low (sequential order) cognitive load interviews. Third-party observers watched these interviews and indicated whether they thought the person was lying or telling the truth. Subjecting participants to a reverse compared to sequential interview increased the misidentification rate and the appearance of cognitive load in truth tellers. People lying about false intentions were not better identified. In Experiment 2, a second set of third-party observers rated behavioral cues. Consistent with Experiment 1, truth tellers, but not liars, exhibited more behaviors associated with lying and fewer behaviors associated with truth telling in the reverse than sequential interview. Together these results suggest that certain cognitively demanding interviews may be less useful when interviewing to detect false intentions. Explaining a true intention while under higher cognitive demand places truth tellers at risk of being misclassified. There may be such a thing as too much cognitive load induced by certain techniques. PMID- 26379609 TI - From specificity to sensitivity: affective states modulate visual working memory for emotional expressive faces. AB - Previous findings suggest that visual working memory (VWM) preferentially remembers angry looking faces. However, the meaning of facial actions is construed in relation to context. To date, there are no studies investigating the role of perceiver-based context when processing emotional cues in VWM. To explore the influence of affective context on VWM for faces, we conducted two experiments using both a VWM task for emotionally expressive faces and a mood induction procedure. Affective context was manipulated by unpleasant (Experiment 1) and pleasant (Experiment 2) IAPS pictures in order to induce an affect high in motivational intensity (defensive or appetitive, respectively) compared to a low arousal control condition. Results indicated specifically increased sensitivity of VWM for angry looking faces in the neutral condition. Enhanced VWM for angry faces was prevented by inducing affects of high motivational intensity. In both experiments, affective states led to a switch from specific enhancement of angry expressions in VWM to an equally sensitive representation of all emotional expressions. Our findings demonstrate that emotional expressions are of different behavioral relevance for the receiver depending on the affective context, supporting a functional organization of VWM along with flexible resource allocation. In VWM, stimulus processing adjusts to situational requirements and transitions from a specifically prioritizing default mode in predictable environments to a sensitive, hypervigilant mode in exposure to emotional events. PMID- 26379611 TI - Grounding grammatical categories: attention bias in hand space influences grammatical congruency judgment of Chinese nominal classifiers. AB - Embodied cognitive theories predict that linguistic conceptual representations are grounded and continually represented in real world, sensorimotor experiences. However, there is an on-going debate on whether this also holds for abstract concepts. Grammar is the archetype of abstract knowledge, and therefore constitutes a test case against embodied theories of language representation. Former studies have largely focussed on lexical-level embodied representations. In the present study we take the grounding-by-modality idea a step further by using reaction time (RT) data from the linguistic processing of nominal classifiers in Chinese. We take advantage of an independent body of research, which shows that attention in hand space is biased. Specifically, objects near the hand consistently yield shorter RTs as a function of readiness for action on graspable objects within reaching space, and the same biased attention inhibits attentional disengagement. We predicted that this attention bias would equally apply to the graspable object classifier but not to the big object classifier. Chinese speakers (N = 22) judged grammatical congruency of classifier-noun combinations in two conditions: graspable object classifier and big object classifier. We found that RTs for the graspable object classifier were significantly faster in congruent combinations, and significantly slower in incongruent combinations, than the big object classifier. There was no main effect on grammatical violations, but rather an interaction effect of classifier type. Thus, we demonstrate here grammatical category-specific effects pertaining to the semantic content and by extension the visual and tactile modality of acquisition underlying the acquisition of these categories. We conclude that abstract grammatical categories are subjected to the same mechanisms as general cognitive and neurophysiological processes and may therefore be grounded. PMID- 26379612 TI - Hair penalties: the negative influence of Afrocentric hair on ratings of Black women's dominance and professionalism. AB - PURPOSE: Women are penalized if they do not behave in a stereotype-congruent manner (Heilman, 1983, 2001; Eagly and Carli, 2007). For example, because women are not expected to be agentic they incur an "agency penalty" for expressing anger, dominance or assertiveness (Rudman, 1998; Rudman and Glick, 1999, 2001; Eagly and Karau, 2002; Rudman and Fairchild, 2004; Brescoll and Uhlmann, 2008; Livingston et al., 2012). Yet, all women are not equally penalized (Livingston et al., 2012). We make a novel contribution by examining how both White and Black evaluators respond to displays of Black women's dominance, in this case, whether Black women choose to wear Afrocentric or Eurocentric hairstyles. DESIGN/METHODOLOGY/APPROACH: We conducted three experimental studies to examine the influence of target hairstyle and participant race on ratings of the target's professionalism (Studies 1, 2, and 3) and dominance (Study 2). Study 1 was an online experimental study with 200 participants (112 females, 87 males, 1 missing gender; 160 Whites, 19 Blacks, 11 Latinos, 7 Asian Americans and 3 who identify as "other"; M age = 35.5, SD = 11.4). Study 2 was an online experimental study with 510 participants (276 women, 234 males; 256 Blacks, 254 Whites; M age = 41.25 years, SD = 12.21). Study 3 was an online experimental study with 291 participants (141 Blacks, 150 Whites, M age = 47.5 years, SD = 11.66). FINDINGS: Black, as compared to White, evaluators gave higher agency penalties to Black employment candidates when they donned Afrocentric versus Eurocentric hair, rating them as more dominant and less professional. IMPLICATIONS: The present research illustrates the significance of considering both target and evaluator race when examining the influence of agency, and specifically dominance, on ratings of professionalism. PMID- 26379613 TI - Perceptual influence of elementary three-dimensional geometry: (1) objectness. AB - Commonly complex cognitive concepts cannot consistently be connected to simple features of the world. Geometrical shape parameters and (e.g., edge features, compactness, color) may play a role for defining individual objects, but might be too variable to allow for concept formation. Earlier works had suggested that the formation of object concepts is strongly influenced by the division of our world along convex to concave surface transitions. In this first paper in a sequence of two we address this issue using abstract 3D geometrical structures (polycubes). In a first experiment, we let our subjects manipulate and compare polycubes with different compactness and different concavity/convexity asking which of them they would perceive as "an object." Both parameters (compactness and concavity/convexity) are not correlated in these stimuli. Nonetheless, we find that subjects with clear prevalence choose compact and convex ones. We continue to ask how strongly this influences the way we construct objects. Thus, in a second experiment we let humans combine polycubes to form an object. Also here we find that they prefer compact and convex configurations. This suggests that this simple geometric feature may underlie our cognitive understanding of objectness not only with respect to perception but also by influencing how we build our world. PMID- 26379614 TI - The precision of 12-month-old infants' link between language and categorization predicts vocabulary size at 12 and 18 months. AB - Infants' initially broad links between language and object categories are increasingly tuned, becoming more precise by the end of their first year. In a longitudinal study, we asked whether individual differences in the precision of infants' links at 12 months of age are related to vocabulary development. We found that, at 12 months, infants who had already established a precise link between labels and categories understood more words than those whose link was still broad. Six months later, this advantage held: At 18 months, infants who had demonstrated a precise link at 12 months knew and produced more words than did infants who had demonstrated a broad link at 12 months. We conclude that individual differences in the precision of 12-month-old infants' links between language and categories provide a reliable window into their vocabulary development. We consider several causal explanations of this relation. PMID- 26379615 TI - Deficits in the Activation of Human Oculomotor Nuclei in Chronic Traumatic Brain Injury. AB - Binocular eye movements form a finely tuned system that requires accurate coordination of the oculomotor dynamics of the brainstem control nuclei when tracking the fine binocular disparities required for 3D vision. They are particularly susceptible to disruption by brain injury and other neural dysfunctions. Here, we report functional magnetic resonance imaging activation of the brainstem oculomotor control nuclei by binocular saccadic and vergence eye movements, and significant reductions in their response amplitudes in mild or diffuse traumatic brain injury (dTBI). Bilateral signals were recorded from a non TBI control group (n = 11) in the oculomotor control system of the superior colliculi, the oculomotor nuclei, the abducens nuclei, and in the supra oculomotor area (SOA), which mediate vergence eye movements. Signals from these nuclei were significantly reduced overall in a dTBI group (n = 12) and in particular for the SOA for vergence movements, which also showed significant decreases in velocity for both the convergence and divergence directions. PMID- 26379616 TI - Central Nervous System and Peripheral Inflammatory Processes in Alzheimer's Disease: Biomarker Profiling Approach. AB - Brain inflammation is one of the hallmarks of Alzheimer disease (AD) and a current trend is that inflammatory mediators, particularly cytokines and chemokines, may represent valuable biomarkers for early screening and diagnosis of the disease. Various studies have reported differences in serum level of cytokines, chemokines, and growth factors in patients with mild cognitive impairment or AD. However, data were often inconsistent and the exact function of inflammation in neurodegeneration is still a matter of debate. In the present work, we measured the expression of 120 biomarkers (corresponding to cytokines, chemokines, growth factors, and related signaling proteins) in the serum of 49 patients with the following diagnosis distribution: 15 controls, 14 AD, and 20 MCI. In addition, we performed the same analysis in the cerebrospinal fluid (CSF) of 20 of these patients (10 AD and 10 controls). Among the biomarkers tested, none showed significant changes in the serum, but 13 were significantly modified in the CSF of AD patients. Interestingly, all of these biomarkers were implicated in neurogenesis or neural stem cells migration and differentiation. In the second part of the study, 10 of these putative biomarkers (plus 4 additional) were quantified using quantitative multiplex ELISA methods in the CSF and the serum of an enlarged cohort composed of 31 AD and 24 control patients. Our results confirm the potential diagnosis interest of previously published blood biomarkers, and proposes new ones (such as IL-8 and TNFR-I). Further studies will be needed to validate these biomarkers which could be used alone, combined, or in association with the classical amyloid and tau biomarkers. PMID- 26379617 TI - Correlation of Resting Elbow Angle with Spasticity in Chronic Stroke Survivors. AB - OBJECTIVE: To evaluate whether resting joint angle is indicative of severity of spasticity of the elbow flexors in chronic stroke survivors. METHODS: Seventeen hemiparetic stroke subjects (male: n = 13; female: n = 4; age: 37-89 years; 11 right and 6 left hemiplegia; averaged 54.8 months after stroke, ranging 12-107 months) participated in the study. The number of subjects with modified Ashworth scale score (MAS) = 0, 1, 1+, 2, and 3 was 3, 3, 5, 3, and 3, respectively. In a single experimental session, resting elbow joint angle, MAS, and Tardieu scale score (Tardieu R1) were measured. A customized motorized stretching device was used to stretch elbow flexors at 5, 50, and 100 degrees /s, respectively. Biomechanical responses (peak reflex torque and reflex stiffness) of elbow flexors were quantified. Correlation analyses between clinical and biomechanical assessments were performed. RESULTS: Resting elbow joint angle showed a strong positive correlation with Tardieu R1 (r = 0.77, p < 0.01) and a very strong negative correlation with MAS (r = -0.89, p < 0.01). The resting angle also had strong correlations with biomechanical measures (r = -0.63 to -0.76, p < 0.01). CONCLUSION: Our study provides experimental evidence for anecdotal observation that the resting elbow joint angle correlates with severity of spasticity in chronic stroke. Resting angle observation for spasticity assessment can and will be an easy, yet a valid way of spasticity estimation in clinical settings, particularly for small muscles or muscles which are not easily measurable by common clinical methods. PMID- 26379618 TI - Lateralization of Temporal Lobe Epilepsy Based on Resting-State Functional Magnetic Resonance Imaging and Machine Learning. AB - Lateralization of temporal lobe epilepsy (TLE) is critical for successful outcome of surgery to relieve seizures. TLE affects brain regions beyond the temporal lobes and has been associated with aberrant brain networks, based on evidence from functional magnetic resonance imaging. We present here a machine learning based method for determining the laterality of TLE, using features extracted from resting-state functional connectivity of the brain. A comprehensive feature space was constructed to include network properties within local brain regions, between brain regions, and across the whole network. Feature selection was performed based on random forest and a support vector machine was employed to train a linear model to predict the laterality of TLE on unseen patients. A leave-one patient-out cross validation was carried out on 12 patients and a prediction accuracy of 83% was achieved. The importance of selected features was analyzed to demonstrate the contribution of resting-state connectivity attributes at voxel, region, and network levels to TLE lateralization. PMID- 26379619 TI - Music Therapy Interventions in Parkinson's Disease: The State-of-the-Art. PMID- 26379622 TI - Changes in the Peripheral Blood Gene Expression Profile Induced by 3 Months of Valproate Treatment in Patients with Newly Diagnosed Epilepsy. AB - Valproic acid (VPA) is a widely used antiepileptic drug with a broad range of effects and broad clinical efficacy. As a well-known histone deacetylase (HDAC) inhibitor, VPA regulates epigenetic programming by altering the expression of many genes. The aim of study was to analyze differences in gene expression profiles before and after the start of VPA treatment in patients with newly diagnosed epilepsy. RNA sequencing was used to compare whole-genome gene expression patterns of peripheral blood from nine patients with epilepsy before and 3 months after the start of treatment with VPA. Of the 23,099 analyzed genes, only 11 showed statistically significant differential expression with false discovery rate-adjusted p-values below 0.1. Functional annotation and network analyses showed activation of only one genetic network (enrichment score = 30), which included genes for cardiovascular system development and function, cell morphology, and hematological system development and function. The finding of such a small number of differently expressed genes between before and after the start of treatment suggests a lack of HDAC inhibition in these patients, which could be explained by the relatively low doses of VPA that were used. In conclusion, VPA at standard therapeutic dosages modulates the expression of a small number of genes. Therefore, to minimize the potential side effects of HDAC inhibition, it is recommended that the lowest effective dose of VPA be used for treating epilepsy. PMID- 26379621 TI - Biochemical Markers of Physical Exercise on Mild Cognitive Impairment and Dementia: Systematic Review and Perspectives. AB - BACKGROUND: The cognitive effects of physical exercise in patients with dementia disorders or mild cognitive impairment have been examined in various studies; however the biochemical effects of exercise from intervention studies are largely unknown. The objective of this systematic review is to investigate the published results on biomarkers in physical exercise intervention studies in patients with MCI or dementia. METHODS: The PubMed database was searched for studies from 1976 to February 2015. We included intervention studies investigating the effect of physical exercise activity on biomarkers in patients with MCI or dementia. RESULTS: A total of eight studies were identified (n = 447 patients) evaluating exercise regimes with variable duration (single session-three sessions/week for 26 weeks) and intensity (light-resistance training-high-intensity aerobic exercise). Various biomarkers were measured before and after intervention. Seven of the eight studies found a significant effect on their selected biomarkers with a positive effect of exercise on brain-derived neurotrophic factor, cholesterol, testosterone, estradiol, dehydroepiadrosterone, and insulin in the intervention groups compared with controls. CONCLUSION: Although few studies suggest a beneficial effect on selected biomarkers, we need more knowledge of the biochemical effect of physical exercise in dementia or MCI. PMID- 26379620 TI - Fluid Biomarkers in Clinical Trials of Alzheimer's Disease Therapeutics. AB - With the demographic shift of the global population toward longer life expectancy, the number of people living with Alzheimer's disease (AD) has rapidly expanded and is projected to triple by the year 2050. Current treatments provide symptomatic relief but do not affect the underlying pathology of the disease. Therapies that prevent or slow the progression of the disease are urgently needed to avoid this growing public health emergency. Insights gained from decades of research have begun to unlock the pathophysiology of this complex disease and have provided targets for disease-modifying therapies. In the last decade, few therapeutic agents designed to modify the underlying disease process have progressed to clinical trials and none have been brought to market. With the focus on disease modification, biomarkers promise to play an increasingly important role in clinical trials. Six biomarkers have now been included in diagnostic criteria for AD and are regularly incorporated into clinical trials. Three biomarkers are neuroimaging measures - hippocampal atrophy measured by magnetic resonance imaging (MRI), amyloid uptake as measured by Pittsburg compound B positron emission tomography (PiB-PET), and decreased fluorodeoxyglucose (18F) uptake as measured by PET (FDG-PET) - and three are sampled from fluid sources - cerebrospinal fluid levels of amyloid beta42 (Abeta42), total tau, and phosphorylated tau. Fluid biomarkers are important because they can provide information regarding the underlying biochemical processes that are occurring in the brain. The purpose of this paper is to review the literature regarding the existing and emerging fluid biomarkers and to examine how fluid biomarkers have been incorporated into clinical trials. PMID- 26379623 TI - Serum from a Patient with GAD65 Antibody-Associated Limbic Encephalitis Did Not Alter GABAergic Neurotransmission in Cultured Hippocampal Networks. AB - BACKGROUND: Glutamate decarboxylase is an intracellular enzyme converting glutamate into GABA. Antibodies (abs) to its isoform GAD65 were described in limbic encephalitis and other neurological conditions. The significance of GAD65 abs for epilepsy is unclear, but alterations of inhibitory GABAergic neurotransmission may be involved. Here, we investigated the effects of the serum of a female patient suffering from GAD65 ab-associated LE on GABAA currents in cultured hippocampal networks. METHODS: Spontaneous or evoked post-synaptic GABAA currents were measured in cultured hippocampal neurons prepared from embryonic mice after 11-21 days in vitro using the patch-clamp technique in the whole-cell mode after incubation with serum of a healthy control or the LE-patient at a final concentration of 1% for 5-8 h. RESULTS: Properties of miniature inhibitory post-synaptic currents were not different in cultures treated with control and LE serum. Likewise, paired-pulse ratio of evoked GABAA currents as a measure of release probability was not different in both conditions. Evoked GABAA currents were significantly depressed during 10 Hz stimulation without significant differences between control and LE-serum treated cultures. CONCLUSION: In our experimental paradigms, serum of a patient with confirmed GAD65 ab-associated LE had no apparent effect on GABAergic neurotransmission in murine-cultured hippocampal networks. These results challenge the view that the presence of GAD65 abs invariably compromise inhibitory network function. PMID- 26379624 TI - Assessing Gonadotropin Receptor Function by Resonance Energy Transfer-Based Assays. AB - Gonadotropin receptors belong to the super family of G protein-coupled receptors and mediate the physiological effects of follicle-stimulating hormone (FSHR) and luteinizing hormone (LHR). Their central role in the control of reproductive function has made them the focus of intensive studies. Upon binding to their cognate hormone, they trigger complex signaling and trafficking mechanisms that are tightly regulated in concentration, time, and space. Classical cellular assays often fail to capture all these dynamics. Here, we describe the use of various bioluminescence and fluorescence resonance energy transfer (BRET and FRET) assays to investigate the activation and regulation of FSHR and LHR in real time, in living cells (i.e., transiently expressed in human embryonic kidney 293 cells). Indeed, the dynamics of hormone-mediated heterotrimeric G protein activation, cyclic adenosine-monophosphate (cAMP) production, calcium release, beta-arrestin 2 recruitment, and receptor internalization/recycling was assessed. Kinetics and dose-response analyses confirmed the expected pharmacological and signaling properties of hFSHR and hLHR but revealed interesting characteristics when considering the two major pathways (cAMP and beta-arrestin 2) of the two receptors assessed by BRET. Indeed, the EC50 values were in picomolar range for cAMP production while nanomolar range was observed for beta-arrestin 2 recruitment as well as receptor internalization. Interestingly, the predicted receptor occupancy indicates that the maximal G protein activation and cAMP response occur at <10% of receptor occupancy whereas >90% of activated receptors is required to achieve full beta-arrestin 2 recruitment and subsequent receptor internalization. The rapid receptor internalization was also followed by a recycling phase. Collectively, our data reveal that beta-arrestin-mediated desensitization, internalization, and the subsequent fast recycling of receptors at the plasma membrane may provide a mechanistic ground to the "spare receptor" paradigm. More generally, the novel tools described here will undoubtedly provide the scientific community investigating gonadotropin receptors with powerful means to decipher their pharmacology and signaling with the prospect of pathophysiological and drug discovery applications. PMID- 26379626 TI - Editorial: Control of Adipocyte Differentiation and Metabolism. PMID- 26379625 TI - LGR4 and Its Role in Intestinal Protection and Energy Metabolism. AB - Leucine-rich repeat-containing G protein-coupled receptors were identified by the unique nature of their long leucine-rich repeat extracellular domains. Distinct from classical G protein-coupled receptors which act via G proteins, LGR4 functions mainly through Wnt/beta-catenin signaling to regulate cell proliferation, differentiation, and adult stem cell homeostasis. LGR4 is widely expressed in tissues ranging from the reproductive system, urinary system, sensory organs, digestive system, and the central nervous system, indicating LGR4 may have multiple functions in development. Here, we focus on the digestive system by reviewing its effects on crypt cells differentiation and stem cells maintenance, which are important for cell regeneration after injury. Through effects on Wnt/beta-catenin signaling and cell proliferation, LGR4 and its endogenous ligands, R-spondins, are involved in colon tumorigenesis. LGR4 also contributes to regulation of energy metabolism, including food intake, energy expenditure, and lipid metabolism, as well as pancreatic beta-cell proliferation and insulin secretion. This review summarizes the identification of LGR4, its endogenous ligand, ligand-receptor binding and intracellular signaling. Physiological functions include intestinal development and energy metabolism. The potential effects of LGR4 and its ligand in the treatment of inflammatory bowel disease, chemoradiotherapy-induced gut damage, colorectal cancer, and diabetes are also discussed. PMID- 26379627 TI - FGF21 and Cardiac Physiopathology. AB - The heart is not traditionally considered either a target or a site of fibroblast growth factor-21 (FGF21) production. However, recent findings indicate that FGF21 can act as a cardiomyokine; that is, it is produced by cardiac cells at significant levels and acts in an autocrine manner on the heart itself. The heart is sensitive to the effects of FGF21, both systemic and locally generated, owing to the expression in cardiomyocytes of beta-Klotho, the key co-receptor known to confer specific responsiveness to FGF21 action. FGF21 has been demonstrated to protect against cardiac hypertrophy, cardiac inflammation, and oxidative stress. FGF21 expression in the heart is induced in response to cardiac insults, such as experimental cardiac hypertrophy and myocardial infarction in rodents, as well as in failing human hearts. Intracellular mechanisms involving PPARalpha and Sirt1 mediate transcriptional regulation of the FGF21 gene in response to exogenous stimuli. In humans, circulating FGF21 levels are elevated in coronary heart disease and atherosclerosis, and are associated with a higher risk of cardiovascular events in patients with type 2 diabetes. These findings provide new insights into the role of FGF21 in the heart and may offer potential therapeutic strategies for cardiac disease. PMID- 26379629 TI - Natural attenuation model and biodegradation for 1,1,1-trichloroethane contaminant in shallow groundwater. AB - Natural attenuation is an effective and feasible technology for controlling groundwater contamination. This study investigated the potential effectiveness and mechanisms of natural attenuation of 1,1,1-trichloroethane (TCA) contaminants in shallow groundwater in Shanghai by using a column simulation experiment, reactive transport model, and 16S rRNA gene clone library. The results indicated that the majority of the contaminant mass was present at 2-6 m in depth, the contaminated area was approximately 1000 m * 1000 m, and natural attenuation processes were occurring at the site. The effluent breakthrough curves from the column experiments demonstrated that the effectiveness of TCA natural attenuation in the groundwater accorded with the advection-dispersion-reaction equation. The kinetic parameter of adsorption and biotic dehydrochlorination of TCA was 0.068 m(3)/kg and 0.0045 d(-1). The contamination plume was predicted to diminish and the maximum concentration of TCA decreased to 280 MUg/L. The bacterial community during TCA degradation in groundwater belonged to Trichococcus, Geobacteraceae, Geobacter, Mucilaginibacter, and Arthrobacter. PMID- 26379628 TI - Hypothalamic Regulation of Brown Adipose Tissue Thermogenesis and Energy Homeostasis. AB - Obesity and diabetes are increasing at an alarming rate worldwide, but the strategies for the prevention and treatment of these disorders remain inadequate. Brown adipose tissue (BAT) is important for cold protection by producing heat using lipids and glucose as metabolic fuels. This thermogenic action causes increased energy expenditure and significant lipid/glucose disposal. In addition, BAT in white adipose tissue (WAT) or beige cells have been found and they also exhibit the thermogenic action similar to BAT. These data provide evidence indicating BAT/beige cells as a potential target for combating obesity and diabetes. Recent discoveries of active BAT and beige cells in adult humans have further highlighted this potential. Growing studies have also shown the importance of central nervous system in the control of BAT thermogenesis and WAT browning using animal models. This review is focused on central neural thermoregulation, particularly addressing our current understanding of the importance of hypothalamic neural signaling in the regulation of BAT/beige thermogenesis and energy homeostasis. PMID- 26379630 TI - Characterization of Chlamydomonas reinhardtii phosphatidylglycerophosphate synthase in Synechocystis sp. PCC 6803. AB - Phosphatidylglycerol (PG) is an indispensable phospholipid class with photosynthetic function in plants and cyanobacteria. However, its biosynthesis in eukaryotic green microalgae is poorly studied. Here, we report the isolation and characterization of two homologs (CrPGP1 and CrPGP2) of phosphatidylglycerophosphate synthase (PGPS), the rate-limiting enzyme in PG biosynthesis, in Chlamydomonas reinhardtii. Heterologous complementation of Synechocystis sp. PCC 6803 pgsA mutant by CrPGP1 and CrPGP2 rescued the PG dependent growth phenotype, but the PG level and its fatty acid composition were not fully rescued in the complemented strains. As well, oxygen evolution activity was not fully recovered, although electron transport activity of photosystem II was restored to the wild-type level. Gene expression study of CrPGP1 and CrPGP2 in nutrient-starved C. reinhardtii showed differential response to phosphorus and nitrogen deficiency. Taken together, these results highlight the distinct and overlapping function of PGPS in cyanobacteria and eukaryotic algae. PMID- 26379631 TI - Formate, acetate, and propionate as substrates for sulfate reduction in sub arctic sediments of Southwest Greenland. AB - Volatile fatty acids (VFAs) are key intermediates in the anaerobic mineralization of organic matter in marine sediments. We studied the role of VFAs in the carbon and energy turnover in the sulfate reduction zone of sediments from the sub arctic Godthabsfjord (SW Greenland) and the adjacent continental shelf in the NE Labrador Sea. VFA porewater concentrations were measured by a new two-dimensional ion chromatography-mass spectrometry method that enabled the direct analysis of VFAs without sample pretreatment. VFA concentrations were low and surprisingly constant (4-6 MUmol L(-1) for formate and acetate, and 0.5 MUmol L(-1) for propionate) throughout the sulfate reduction zone. Hence, VFAs are turned over while maintaining a stable concentration that is suggested to be under a strong microbial control. Estimated mean diffusion times of acetate between neighboring cells were <1 s, whereas VFA turnover times increased from several hours at the sediment surface to several years at the bottom of the sulfate reduction zone. Thus, diffusion was not limiting the VFA turnover. Despite constant VFA concentrations, the Gibbs energies (DeltaGr) of VFA-dependent sulfate reduction decreased downcore, from -28 to -16 kJ (mol formate)(-1), -68 to -31 kJ (mol acetate)(-1), and -124 to -65 kJ (mol propionate)(-1). Thus, DeltaGr is apparently not determining the in-situ VFA concentrations directly. However, at the bottom of the sulfate zone of the shelf station, acetoclastic sulfate reduction might operate at its energetic limit at ~ -30 kJ (mol acetate)(-1). It is not clear what controls VFA concentrations in the porewater but cell physiological constraints such as energetic costs of VFA activation or uptake could be important. We suggest that such constraints control the substrate turnover and result in a minimum DeltaGr that depends on cell physiology and is different for individual substrates. PMID- 26379632 TI - Overproduction of the membrane-bound [NiFe]-hydrogenase in Thermococcus kodakarensis and its effect on hydrogen production. AB - The hyperthermophilic archaeon Thermococcus kodakarensis can utilize sugars or pyruvate for growth. In the absence of elemental sulfur, the electrons via oxidation of these substrates are accepted by protons, generating molecular hydrogen (H2). The hydrogenase responsible for this reaction is a membrane-bound [NiFe]-hydrogenase (Mbh). In this study, we have examined several possibilities to increase the protein levels of Mbh in T. kodakarensis by genetic engineering. Highest levels of intracellular Mbh levels were achieved when the promoter of the entire mbh operon (TK2080-TK2093) was exchanged to a strong constitutive promoter from the glutamate dehydrogenase gene (TK1431) (strain MHG1). When MHG1 was cultivated under continuous culture conditions using pyruvate-based medium, a nearly 25% higher specific hydrogen production rate (SHPR) of 35.3 mmol H2 g-dcw( 1) h(-1) was observed at a dilution rate of 0.31 h(-1). We also combined mbh overexpression using an even stronger constitutive promoter from the cell surface glycoprotein gene (TK0895) with disruption of the genes encoding the cytosolic hydrogenase (Hyh) and an alanine aminotransferase (AlaAT), both of which are involved in hydrogen consumption (strain MAH1). At a dilution rate of 0.30 h(-1), the SHPR was 36.2 mmol H2 g-dcw(-1) h(-1), corresponding to a 28% increase compared to that of the host T. kodakarensis strain. Increasing the dilution rate to 0.83 h(-1) or 1.07 h(-1) resulted in a SHPR of 120 mmol H2 g-dcw(-1) h(-1), which is one of the highest production rates observed in microbial fermentation. PMID- 26379633 TI - Combination of RNAseq and SNP nanofluidic array reveals the center of genetic diversity of cacao pathogen Moniliophthora roreri in the upper Magdalena Valley of Colombia and its clonality. AB - Moniliophthora roreri is the fungal pathogen that causes frosty pod rot (FPR) disease of Theobroma cacao L., the source of chocolate. FPR occurs in most of the cacao producing countries in the Western Hemisphere, causing yield losses up to 80%. Genetic diversity within the FPR pathogen population may allow the population to adapt to changing environmental conditions and adapt to enhanced resistance in the host plant. The present study developed single nucleotide polymorphism (SNP) markers from RNASeq results for 13 M. roreri isolates and validated the markers for their ability to reveal genetic diversity in an international M. roreri collection. The SNP resources reported herein represent the first study of RNA sequencing (RNASeq)-derived SNP validation in M. roreri and demonstrates the utility of RNASeq as an approach for de novo SNP identification in M. roreri. A total of 88 polymorphic SNPs were used to evaluate the genetic diversity of 172 M. roreri cacao isolates resulting in 37 distinct genotypes (including 14 synonymous groups). Absence of heterozygosity for the 88 SNP markers indicates reproduction in M. roreri is clonal and likely due to a homothallic life style. The upper Magdalena Valley of Colombia showed the highest levels of genetic diversity with 20 distinct genotypes of which 13 were limited to this region, and indicates this region as the possible center of origin for M. roreri. PMID- 26379634 TI - The diversity of PAH-degrading bacteria in a deep-sea water column above the Southwest Indian Ridge. AB - The bacteria involved in organic pollutant degradation in pelagic deep-sea environments are largely unknown. In this report, the diversity of polycyclic aromatic hydrocarbon (PAH)-degrading bacteria was analyzed in deep-sea water on the Southwest Indian Ridge (SWIR). After enrichment with a PAH mixture (phenanthrene, anthracene, fluoranthene, and pyrene), nine bacterial consortia were obtained from depths of 3946-4746 m. While the consortia degraded all four PAHs when supplied in a mixture, when PAHs were tested individually, only phenanthrene supported growth. Thus, degradation of the PAH mixture reflected a cometabolism of anthracene, fluoranthene, and pyrene with phenanthrene. Further, both culture-dependent and independent methods revealed many new bacteria involved in PAH degradation. Specifically, the alpha and gamma subclasses of Proteobacteria were confirmed as the major groups within the communities. Additionally, Actinobacteria, the CFB group and Firmicutes were detected. Denaturing Gradient Gel Electrophoresis (DGGE) analysis showed that bacteria closely affiliated with Alcanivorax, Novosphingobium, and Rhodovulum occurred most frequently in different PAH-degrading consortia. By using general heterotrophic media, 51 bacteria were isolated from the consortia and of these 34 grew with the PAH mixture as a sole carbon source. Of these, isolates most closely related to Alterierythrobacter, Citricella, Erythrobacter, Idiomarina, Lutibacterium, Maricaulis, Marinobacter, Martelella, Pseudidiomarina, Rhodobacter, Roseovarius, Salipiger, Sphingopyxis, and Stappia were found to be PAH degraders. To the best of our knowledge, this is the first time these bacteria have been identified in this context. In summary, this report revealed significant diversity among the PAH-degrading bacteria in the deep-sea water column. These bacteria may play a role in PAH removal in deep-sea environments. PMID- 26379635 TI - Response of leaf endophytic bacterial community to elevated CO2 at different growth stages of rice plant. AB - Plant endophytic bacteria play an important role in plant growth and health. In the context of climate change, the response of plant endophytic bacterial communities to elevated CO2 at different rice growing stages is poorly understood. Using 454 pyrosequencing, we investigated the response of leaf endophytic bacterial communities to elevated CO2 (eCO2) at the tillering, filling, and maturity stages of the rice plant under different nitrogen fertilization conditions [low nitrogen fertilization (LN) and high nitrogen fertilization (HN)]. The results revealed that the leaf endophytic bacterial community was dominated by Gammaproteobacteria-affiliated families, such as Enterobacteriaceae and Xanthomonadaceae, which represent 28.7-86.8% and 2.14 42.6% of the total sequence reads, respectively, at all tested growth stages. The difference in the bacterial community structure between the different growth stages was greater than the difference resulting from the CO2 and nitrogen fertilization treatments. The eCO2 effect on the bacterial communities differed greatly under different nitrogen application conditions and at different growth stages. Specifically, eCO2 revealed a significant effect on the community structure under both LN and HN levels at the tillering stage; however, the significant effect of eCO2 was only observed under HN, rather than under the LN condition at the filling stage; no significant effect of eCO2 on the community structure at both the LN and HN fertilization levels was found at the maturity stage. These results provide useful insights into the response of leaf endophytic bacterial communities to elevated CO2 across rice growth stages. PMID- 26379637 TI - Microbial mineral colonization across a subsurface redox transition zone. AB - This study employed 16S rRNA gene amplicon pyrosequencing to examine the hypothesis that chemolithotrophic Fe(II)-oxidizing bacteria (FeOB) would preferentially colonize the Fe(II)-bearing mineral biotite compared to quartz sand when the minerals were incubated in situ within a subsurface redox transition zone (RTZ) at the Hanford 300 Area site in Richland, WA, USA. The work was motivated by the recently documented presence of neutral-pH chemolithotrophic FeOB capable of oxidizing structural Fe(II) in primary silicate and secondary phyllosilicate minerals in 300 Area sediments and groundwater (Benzine et al., 2013). Sterilized portions of sand+biotite or sand alone were incubated in situ for 5 months within a multilevel sampling (MLS) apparatus that spanned a ca. 2-m interval across the RTZ in two separate groundwater wells. Parallel MLS measurements of aqueous geochemical species were performed prior to deployment of the minerals. Contrary to expectations, the 16S rRNA gene libraries showed no significant difference in microbial communities that colonized the sand+biotite vs. sand-only deployments. Both mineral-associated and groundwater communities were dominated by heterotrophic taxa, with organisms from the Pseudomonadaceae accounting for up to 70% of all reads from the colonized minerals. These results are consistent with previous results indicating the capacity for heterotrophic metabolism (including anaerobic metabolism below the RTZ) as well as the predominance of heterotrophic taxa within 300 Area sediments and groundwater. Although heterotrophic organisms clearly dominated the colonized minerals, several putative lithotrophic (NH4 (+), H2, Fe(II), and HS(-) oxidizing) taxa were detected in significant abundance above and within the RTZ. Such organisms may play a role in the coupling of anaerobic microbial metabolism to oxidative pathways with attendant impacts on elemental cycling and redox-sensitive contaminant behavior in the vicinity of the RTZ. PMID- 26379638 TI - Differential response of kabuli and desi chickpea genotypes toward inoculation with PGPR in different soils. AB - Pakistan is among top three chickpea producing countries but the crop is usually grown on marginal lands without irrigation and fertilizer application which significantly hampers its yield. Soil fertility and inoculation with beneficial rhizobacteria play a key role in nodulation and yield of legumes. Four kabuli and six desi chickpea genotypes were, therefore, evaluated for inoculation response with IAA-producing Ochrobactrum ciceri Ca-34(T) and nitrogen fixing Mesorhizobium ciceri TAL-1148 in single and co-inoculation in two soils. The soil type 1 was previously unplanted marginal soil having low organic matter, P and N contents compared to soil type 2 which was a fertile routinely legume-cultivated soil. The effect of soil fertility status was pronounced and fertile soil on average, produced 31% more nodules, 62% more biomass and 111% grain yield than marginal soil. Inoculation either with O. ciceri alone or its co-inoculation with M. ciceri produced on average higher nodules (42%), biomass (31%), grains yield (64%) and harvest index (72%) in both chickpea genotypes over non-inoculated controls in both soils. Soil 1 showed maximum relative effectiveness of Ca-34(T) inoculation for kabuli genotypes while soil 2 showed for desi genotypes except B8/02. Desi genotype B8/02 in soil type 1 and Pb-2008 in soil type 2 showed significant yield increase as compared to respective un-inoculated controls. Across bacterial inoculation treatments, grain yield was positively correlated to growth and yield contributing parameters (r = 0.294(*) to 0.838(***) for desi and r = 0.388(*) to 0.857(**) for kabuli). PCA and CAT-PCA analyses clearly showed a site-specific response of genotype x bacterial inoculation. Furthermore, the inoculated bacterial strains were able to persist in the rhizosphere showing colonization on root and within nodules. Present study shows that plant growth promoting rhizobacteria (PGPR) inoculation should be integrated with national chickpea breading program in Pakistan especially for marginal soils. Furthermore, the study shows the potential of phytohormone producing strain Ca-34(T) as promising candidate for development of biofertilizer alongwith nodulating strains to get sustainable yield of kabuli and desi chickpea with minimum inputs at marginal land. PMID- 26379636 TI - Microbial diversity in a submarine carbonate edifice from the serpentinizing hydrothermal system of the Prony Bay (New Caledonia) over a 6-year period. AB - Active carbonate chimneys from the shallow marine serpentinizing Prony Hydrothermal Field were sampled 3 times over a 6 years period at site ST09. Archaeal and bacterial communities composition was investigated using PCR-based methods (clone libraries, Denaturating Gel Gradient Electrophoresis, quantitative PCR) targeting 16S rRNA genes, methyl coenzyme M reductase A and dissimilatory sulfite reductase subunit B genes. Methanosarcinales (Euryarchaeota) and Thaumarchaea were the main archaeal members. The Methanosarcinales, also observed by epifluorescent microscopy and FISH, consisted of two phylotypes that were previously solely detected in two other serpentinitzing ecosystems (The Cedars and Lost City Hydrothermal Field). Surprisingly, members of the hyperthermophilic order Thermococcales were also found which may indicate the presence of a hot subsurface biosphere. The bacterial community mainly consisted of Firmicutes, Chloroflexi, Alpha-, Gamma-, Beta-, and Delta-proteobacteria and of the candidate division NPL-UPA2. Members of these taxa were consistently found each year and may therefore represent a stable core of the indigenous bacterial community of the PHF chimneys. Firmicutes isolates representing new bacterial taxa were obtained by cultivation under anaerobic conditions. Our study revealed diverse microbial communities in PHF ST09 related to methane and sulfur compounds that share common populations with other terrestrial or submarine serpentinizing ecosystems. PMID- 26379639 TI - Recent trends and perspectives of molecular markers against fungal diseases in wheat. AB - Wheat accounts for 19% of the total production of major cereal crops in the world. In view of ever increasing population and demand for global food production, there is an imperative need of 40-60% increase in wheat production to meet the requirement of developing world in coming 40 years. However, both biotic and abiotic stresses are major hurdles for attaining the goal. Among the most important diseases in wheat, fungal diseases pose serious threat for widening the gap between actual and attainable yield. Fungal disease management, mainly, depends on the pathogen detection, genetic and pathological variability in population, development of resistant cultivars and deployment of effective resistant genes in different epidemiological regions. Wheat protection and breeding of resistant cultivars using conventional methods are time-consuming, intricate and slow processes. Molecular markers offer an excellent alternative in development of improved disease resistant cultivars that would lead to increase in crop yield. They are employed for tagging the important disease resistance genes and provide valuable assistance in increasing selection efficiency for valuable traits via marker assisted selection (MAS). Plant breeding strategies with known molecular markers for resistance and functional genomics enable a breeder for developing resistant cultivars of wheat against different fungal diseases. PMID- 26379640 TI - Response of bacterioplankton to iron fertilization of the Southern Ocean, Antarctica. AB - Ocean iron fertilization is an approach to increase CO2 sequestration. The Indo German iron fertilization experiment "LOHAFEX" was carried out in the Southern Ocean surrounding Antarctica in 2009 to monitor changes in bacterial community structure following iron fertilization-induced phytoplankton bloom of the seawater from different depths. 16S rRNA gene libraries were constructed using metagenomic DNA from seawater prior to and after iron fertilization and the clones were sequenced for identification of the major bacterial groups present and for phylogenetic analyses. A total of 4439 clones of 16S rRNA genes from ten 16S rRNA gene libraries were sequenced. More than 97.35% of the sequences represented four bacterial lineages i.e. Alphaproteobacteria, Gammaproteobacteria, Bacteroidetes, and Firmicutes and confirmed their role in scavenging of phytoplankton blooms induced following iron fertilization. The present study demonstrates the response of Firmicutes due to Iron fertilization which was not observed in previous southern ocean Iron fertilization studies. In addition, this study identifies three unique phylogenetic clusters LOHAFEX Cluster 1 (affiliated to Bacteroidetes), 2, and 3 (affiliated to Firmicutes) which were not detected in any of the earlier studies on iron fertilization. The relative abundance of these clusters in response to iron fertilization was different. The increase in abundance of LOHAFEX Cluster 2 and Papillibacter sp. another dominant Firmicutes may imply a role in phytoplankton degradation. Disappearance of LOHAFEX Cluster 3 and other bacterial genera after iron fertilization may imply conditions not conducive for their survival. It is hypothesized that heterotrophic bacterial abundance in the Southern Ocean would depend on their ability to utilize algal exudates, decaying algal biomass and other nutrients thus resulting in a dynamic bacterial succession of distinct genera. PMID- 26379641 TI - The horizontal transfer of antibiotic resistance genes is enhanced by ionic liquid with different structure of varying alkyl chain length. AB - Antibiotic resistance genes (ARGs) have become a global health concern. In our previous study, an ionic liquid (IL) 1-butyl-3-methylimidazolium hexafluorophosphate ([BMIm][PF6]) had been proven to facilitate the dissemination of ARGs in the environment. However, enhanced alkyl group chain length or the substitution of alkyl groups with the cation ring corresponded with increased antimicrobial effects. In this study, we investigated how different structures of ILs with 4, 6, and 8 C atoms in the longer alkyl chain on the imidazolium cations facilitated the dissemination of ARGs. The promotion of plasmid RP4 transfer frequency decreased with [CnMIM][BF4] increasing the alkyl chain length from 4 carbon atoms to 8 carbon atoms on the imidazolium cations, which is observed with [BMIM][BF4] (n = 4, 5.9 fold) > HMIM][BF4] (n = 6, 2.2 fold) > [OMIM][BF4] (n = 8, 1.7 fold). This illustrates that [CnMIM][BF4] with increasing the alkyl chain length exert decreasing ability in facilitating plasmid RP4 horizontal transfer, which is possibly related to IL-structure dependent toxicity. The IL-structure dependent plasmid RP4 transfer frequency was attributable to bacterial cell membrane permeability weaken with increasing alkyl chain length of [CnMIM][PF4], which was evidenced by flow cytometry. In freshwater microcosm, [CnMIm][BF4] promoted the relative abundance of the sulI and intI genes for 4.6 folds, aphA and traF for 5.2 folds higher than the untreated groups, promoting the propagation of ARGs in the aquatic environment. This is the first report that ILs with different structure of varying alkyl chain length facilitate horizontal transfer of plasmid RP4 which is widely distributed in the environment, and thus add the adverse effects of the environmental risk of ILs. PMID- 26379642 TI - Warming reduces the cover and diversity of biocrust-forming mosses and lichens, and increases the physiological stress of soil microbial communities in a semi arid Pinus halepensis plantation. AB - Soil communities dominated by lichens and mosses (biocrusts) play key roles in maintaining ecosystem structure and functioning in drylands worldwide. However, few studies have explicitly evaluated how climate change-induced impacts on biocrusts affect associated soil microbial communities. We report results from a field experiment conducted in a semiarid Pinus halepensis plantation, where we setup an experiment with two factors: cover of biocrusts (low [<15%] versus high [>50%]), and warming (control versus a ~2 degrees C temperature increase). Warming reduced the richness and cover (~45%) of high biocrust cover areas 53 months after the onset of the experiment. This treatment did not change the ratios between the major microbial groups, as measured by phospholipid fatty acid analysis. Warming increased the physiological stress of the Gram negative bacterial community, as indicated by the cy17:0/16:1omega7 ratio. This response was modulated by the initial biocrust cover, as the increase in this ratio with warming was higher in areas with low cover. Our findings suggest that biocrusts can slow down the negative effects of warming on the physiological status of the Gram negative bacterial community. However, as warming will likely reduce the cover and diversity of biocrusts, these positive effects will be reduced under climate change. PMID- 26379643 TI - Pseudomonas aeruginosa inhibits the growth of Scedosporium aurantiacum, an opportunistic fungal pathogen isolated from the lungs of cystic fibrosis patients. AB - The filamentous fungus Scedosporium aurantiacum and the bacterium Pseudomonas aeruginosa are opportunistic pathogens isolated from lungs of the cystic fibrosis (CF) patients. P. aeruginosa has been known to suppress the growth of a number of CF related fungi such as Aspergillus fumigatus, Candida albicans, and Cryptococcus neoformans. However, the interactions between P. aeruginosa and S. aurantiacum have not been investigated in depth. Hence we assessed the effect of P. aeruginosa reference strain PAO1 and two clinical isolates PASS1 and PASS2 on the growth of two clinical S. aurantiacum isolates WM 06.482 and WM 08.202 using solid plate assays and liquid cultures, in a synthetic medium mimicking the nutrient condition in the CF sputum. Solid plate assays showed a clear inhibition of growth of both S. aurantiacum strains when cultured with P. aeruginosa strains PASS1 and PAO1. The inhibitory effect was confirmed by confocal microscopy. In addition to using chemical fluorescent stains, strains tagged with yfp (P. aeruginosa PASS1) and mCherry (S. aurantiacum WM 06.482) were created to facilitate detailed microscopic observations on strain interaction. To our knowledge, this is the first study describing successful genetic transformation of S. aurantiacum. Inhibition of growth was observed only in co-cultures of P. aeruginosa and S. aurantiacum; the cell fractions obtained from independent bacterial monocultures failed to initiate a response against the fungus. In the liquid co-cultures, biofilm forming P. aeruginosa strains PASS1 and PAO1 displayed higher inhibition of fungal growth when compared to PASS2. No change was observed in the inhibition pattern when direct cell contact between the bacterial and fungal strains was prevented using a separation membrane suggesting the involvement of extracellular metabolites in the fungal inhibition. However, one of the most commonly described bacterial virulence factors, pyocyanin, had no effect against either of the S. aurantiacum strains. This study shows that P. aeruginosa has a substantial inhibitory effect on the growth of the recently described CF fungal pathogen S. aurantiacum. The findings also highlighted that P. aeruginosa biofilm formation is important but not crucial for inhibiting the growth of S. aurantiacum in a lung- mimicking environment. PMID- 26379644 TI - Effects of growth stage and fulvic acid on the diversity and dynamics of endophytic bacterial community in Stevia rebaudiana Bertoni leaves. AB - The aim of this study was to learn the interactions among the endophytic bacteria, the plant growth, the foliar spray of fulvic acid, and the accumulation of steviol glycosides in the leaves of Stevia rebaudiana. Metagenomic DNA was extracted from the Stevia leaves at different growth stages with or without the fulvic acid treatment; and the diversity of endophytic bacteria in Stevia leaves was estimated by pyrosequencing of 16S rRNA genes. As results, Proteobacteria, Actinobacteria, Bacteroidetes, and Firmicutes were found to be the dominant phyla despite the growth stages and fulvic acid application. Stevia growth stages strongly regulated composition of endophytic community. The genera Agrobacterium (12.3%) and Erwinia (7.2%) dominated in seedling stage were apparently declined in the vegetable and initial flowering stages, while Sphingomonas and Methylobacterium increased in mature leaves at harvest time, which showed that the mature leaves of Stevia preferred to accumulate some certain endophytic bacteria. Sphingomonas and Methylobacterium constituted an important part of the core endophytic community and were positively correlated with the stevioside content and UGT74G1 gene expression, respectively; while Erwinia, Agrobacterium, and Bacillus were negatively correlated with the stevioside accumulation. Fulvic acid treatment accelerated the variation of endophytes along the growth stages and increased the steviol glycosides content. This is the first study to reveal the community composition of endophytic bacteria in the Stevia leaves, to evidence the strong effects of growth stage and fulvic acid application on the endophytes of Stevia, and to demonstrate the correlation between the endophytic bacteria and the steviol glycosides accumulation. PMID- 26379645 TI - Rapidly diverging evolution of an atypical alkaline phosphatase (PhoA(aty)) in marine phytoplankton: insights from dinoflagellate alkaline phosphatases. AB - Alkaline phosphatase (AP) is a key enzyme that enables marine phytoplankton to scavenge phosphorus (P) from dissolved organic phosphorus (DOP) when inorganic phosphate is scarce in the ocean. Yet how the AP gene has evolved in phytoplankton, particularly dinoflagellates, is poorly understood. We sequenced full-length AP genes and corresponding complementary DNA (cDNA) from 15 strains (10 species), representing four classes of the core dinoflagellate lineage, Gymnodiniales, Prorocentrales, Suessiales, and Gonyaulacales. Dinoflagellate AP gene sequences exhibited high variability, containing variable introns, pseudogenes, single nucleotide polymorphisms and consequent variations in amino acid sequence, indicative of gene duplication events and consistent with the "birth-and-death" model of gene evolution. Further sequence comparison showed that dinoflagellate APs likely belong to an atypical type AP (PhoA(aty)), which shares conserved motifs with counterparts in marine bacteria, cyanobacteria, green algae, haptophytes, and stramenopiles. Phylogenetic analysis suggested that PhoA(aty) probably originated from an ancestral gene in bacteria and evolved divergently in marine phytoplankton. Because variations in AP amino acid sequences may lead to differential subcellular localization and potentially different metal ion requirements, the multiple types of APs in algae may have resulted from selection for diversifying strategies to utilize DOP in the P variable marine environment. PMID- 26379646 TI - Analysis of the pathogenic potential of nosocomial Pseudomonas putida strains. AB - Pseudomonas putida strains are ubiquitous in soil and water but have also been reported as opportunistic human pathogens capable of causing nosocomial infections. In this study we describe the multilocus sequence typing of four P. putida strains (HB13667, HB8234, HB4184, and HB3267) isolated from in-patients at the Besancon Hospital (France). The four isolates (in particular HB3267) were resistant to a number of antibiotics. The pathogenicity and virulence potential of the strains was tested ex vivo and in vivo using different biological models: human tissue culture, mammalian tissues, and insect larvae. Our results showed a significant variability in the ability of the four strains to damage the host; HB13667 did not exhibit any pathogenic traits, HB4184 caused damage only ex vivo in human tissue cultures, and HB8234 had a deleterious effect in tissue culture and in vivo on rat skin, but not in insect larvae. Interestingly, strain HB3267 caused damage in all the model systems studied. The putative evolution of these strains in medical environments is discussed. PMID- 26379647 TI - Abundant Atribacteria in deep marine sediment from the Adelie Basin, Antarctica. AB - Bacteria belonging to the newly classified candidate phylum "Atribacteria" (formerly referred to as "OP9" and "JS1") are common in anoxic methane-rich sediments. However, the metabolic functions and biogeochemical role of these microorganisms in the subsurface remains unrealized due to the lack of pure culture representatives. In this study of deep sediment from Antarctica's Adelie Basin, collected during Expedition 318 of the Integrated Ocean Drilling Program (IODP), Atribacteria-related sequences of the 16S rRNA gene were abundant (up to 51% of the sequences) and steadily increased in relative abundance with depth throughout the methane-rich zones. To better understand the metabolic potential of Atribacteria within this environment, and to compare with phylogenetically distinct Atribacteria from non-deep-sea environments, individual cells were sorted for single cell genomics from sediment collected from 97.41 m below the seafloor from IODP Hole U1357C. As observed for non-marine Atribacteria, a partial single cell genome suggests a heterotrophic metabolism, with Atribacteria potentially producing fermentation products such as acetate, ethanol, and CO2. These products may in turn support methanogens within the sediment microbial community and explain the frequent occurrence of Atribacteria in anoxic methane rich sediments. This first report of a single cell genome from deep sediment broadens the known diversity within the Atribacteria phylum and highlights the potential role of Atribacteria in carbon cycling in deep sediment. PMID- 26379648 TI - Presence of toxic microbial metabolites in table olives. AB - Table olives have an enormous importance in the diet and culture of many Mediterranean countries. Albeit there are different ways to produce this fermented vegetable, brining/salting, fermentation, and acidification are common practices for all of them. Preservation methods such as pasteurization or sterilization are frequently used to guarantee the stability and safety of fermented olives. However, final products are not always subjected to a heat treatment. Thus, microbiota is not always removed and appropriate levels of acidity and salt must be obtained before commercialization. Despite the physicochemical conditions not being favorable for the growth of foodborne pathogens, some illness outbreaks have been reported in the literature. Street markets, inappropriate manipulation and storage conditions were the origin of many of the samples in which foodborne pathogens or their metabolites were detected. Many authors have also studied the survival of pathogens in different styles of table olive elaboration, finding in general that olive environment is not appropriate for their presence. Inhibitory compounds such as polyphenols, low availability of nutrients, high salt content, low pH levels, bacteriocins, or the addition of preservatives act as hurdles against undesirable microorganisms, which contribute to obtaining a safe and good quality product. PMID- 26379649 TI - Genetic islands in pome fruit pathogenic and non-pathogenic Erwinia species and related plasmids. AB - New pathogenic bacteria belonging to the genus Erwinia associated with pome fruit trees (Erwinia, E. piriflorinigrans, E. uzenensis) have been increasingly described in the last years, and comparative analyses have found that all these species share several genetic characteristics. Studies at different level (whole genome comparison, virulence genes, plasmid content, etc.) show a high intraspecies homogeneity (i.e., among E. amylovora strains) and also abundant similarities appear between the different Erwinia species: presence of plasmids of similar size in the pathogenic species; high similarity in several genes associated with exopolysaccharide production and hence, with virulence, as well as in some other genes, in the chromosomes. Many genetic similarities have been observed also among some of the plasmids (and genomes) from the pathogenic species and E. tasmaniensis or E. billingiae, two epiphytic species on the same hosts. The amount of genetic material shared in this genus varies from individual genes to clusters, genomic islands and genetic material that even may constitute a whole plasmid. Recent research on evolution of erwinias point out the horizontal transfer acquisition of some genomic islands that were subsequently lost in some species and several pathogenic traits that are still present. How this common material has been obtained and is efficiently maintained in different species belonging to the same genus sharing a common ecological niche provides an idea of the origin and evolution of the pathogenic Erwinia and the interaction with non-pathogenic species present in the same niche, and the role of the genes that are conserved in all of them. PMID- 26379650 TI - Variation in the nuclear effects of infection by different human rhinovirus serotypes. AB - Human rhinovirus (HRV) is a positive sense RNA virus, which, despite replicating in the cytoplasm, has a significant impact on nuclear transport and nuclear localization of host proteins. A number of studies have identified differences between HRV serotypes, with respect to host response, protease activity and replicative ability. Here we report the sero-specific effects of two group-A HRV serotypes, the minor group HRV2 and the major group HRV16, on nuclear transport and nuclear protein localization. Using Western analysis, immunofluorescence and real time PCR, we show that HRV2 replicates at a faster rate than HRV16, which correlates with earlier production of viral proteases and disruption of host nuclear transport. There is significant variation in the nuclear effects of different rhinovirus species, which in turn may impact disease progression and patient response. PMID- 26379651 TI - Purification and synergistic antibacterial activity of arginine derived cyclic dipeptides, from Achromobacter sp. associated with a rhabditid entomopathogenic nematode against major clinically relevant biofilm forming wound bacteria. AB - Skin and chronic wound infections caused by various pathogenic bacteria are an increasing and urgent health problem worldwide. In the present investigation ethyl acetate extract of an Achromobacter sp. associated with a Rhabditis entomopathogenic nematode (EPN), displayed promising antibacterial property and was further purified by silica gel column chromatography to get three different cyclic dipeptides (CDPs). Based on the spectral data and Marfey's analyses, the CDPs were identified as cyclo(D-Leu-D-Arg) (1), cyclo(L-Trp-L-Arg) (2), and cyclo(D-Trp-D-Arg) (3), respectively. Three CDPs were active against all the 10 wound associated bacteria tested. The significant antibacterial activity was recorded by CDP 3, and highest activity of 0.5 MUg/ml was recorded against Staphylococcus aureus and Pseudomonas aeruginosa. The synergistic antibacterial activities of CDPs and ampicillin were assessed using the checkerboard microdilution method. The results of the current study recorded that the combined effects of CDPs and ampicillin principally recorded synergistic activity. Interestingly, the combination of CDPs and ampicillin also recorded enhanced inhibition of biofilm formation by bacteria. Moreover, CDPs significantly stimulate the production of IL-10 and IL-4 (anti-inflammatory cytokines) by human peripheral blood mononuclear cells. CDPs do not make any significant effect on the production of pro-inflammatory cytokines like TNF-alpha. The three CDPs have been studied for their effect on intracellular S. aureus in murine macrophages (J774) using 24 h exposure to 0.5X, 1X, and 2X MIC concentrations. Significant decrease in intracellular S. aureus burden was recorded by CDPs. CDPs also recorded no cytotoxicity toward FS normal fibroblast, VERO, and L231 normal lung epithelial cell lines. Antimicrobial activity of the arginine containing CDPs against the wound associated bacteria is reported here for the first. Moreover, this is also the first report on the production of CDPs by Achromobacter sp. Finally, we conclude that the Achromobacter sp. is an incredibly promising source of natural bioactive secondary metabolites especially against wound pathogenic bacteria that may receive significant benefit in the field of human medicine in near future as topical agents. PMID- 26379652 TI - Responses in colonic microbial community and gene expression of pigs to a long term high resistant starch diet. AB - Intake of raw potato starch (RPS) has been associated with various intestinal health benefits, but knowledge of its mechanism in a long-term is limited. The aim of this study was to investigate the effects of long-term intake of RPS on microbial composition, genes expression profiles in the colon of pigs. Thirty-six Duroc * Landrace * Large White growing barrows were randomly allocated to corn starch (CS) and RPS groups with a randomized block design. Each group consisted of six replicates (pens), with three pigs per pen. Pigs in the CS group were offered a corn/soybean-based diet, while pigs in the RPS group were put on a diet in which 230 g/kg (growing period) or 280 g/kg (finishing period) purified CS was replaced with purified RPS during a 100-day trial. Real-time PCR assay showed that RPS significantly decreased the number of total bacteria in the colonic digesta. MiSeq sequencing of the V3-V4 region of the 16S rRNA genes showed that RPS significantly decreased the relative abundance of Clostridium, Treponema, Oscillospira, Phascolarctobacterium, RC9 gut group, and S24-7-related operational taxonomic units (OTUs), and increased the relative abundance of Turicibacter, Blautia, Ruminococcus, Coprococcus, Marvinbryantia, and Ruminococcus bromii related OTUs in colonic digesta and mucosa. Analysis of the colonic transcriptome profiles revealed that the RPS diet changed the colonic expression profile of the host genes mainly involved in immune response pathways. RPS significantly increased proinflammartory cytokine IL-1beta gene expression and suppressed genes involved in lysosome. Our findings suggest that long-term intake of high resistant starch (RS) diet may result in both positive and negative roles in gut health. PMID- 26379653 TI - The dual action of poly(ADP-ribose) polymerase -1 (PARP-1) inhibition in HIV-1 infection: HIV-1 LTR inhibition and diminution in Rho GTPase activity. AB - Multifactorial mechanisms comprising countless cellular factors and virus-encoded transactivators regulate the transcription of HIV-1 (HIV). Since poly(ADP-ribose) polymerase 1 (PARP-1) regulates numerous genes through its interaction with various transcription factors, inhibition of PARP-1 has surfaced recently as a powerful anti-inflammatory tool. We suggest a novel tactic to diminish HIV replication via PARP-1 inhibition in an in vitro model system, exploiting human primary monocyte-derived macrophages (MDM). PARP-1 inhibition was capable to lessen HIV replication in MDM by 60-80% after 7 days infection. Tat, tumor necrosis factor alpha (TNFalpha), and phorbol 12-myristate 13-acetate (PMA) are known triggers of the Long Terminal Repeat (LTR), which can switch virus replication. Tat overexpression in MDM transfected with an LTR reporter plasmid resulted in a 4.2-fold increase in LTR activation; PARP inhibition caused 70% reduction of LTR activity. LTR activity, which increased 3-fold after PMA or TNFalpha treatment, was reduced by PARP inhibition (by 85-95%). PARP inhibition in MDM exhibited 90% diminution in NFkappaB activity (known to mediate TNFalpha- and PMA-induced HIV LTR activation). Cytoskeleton rearrangements are important in effective HIV-1 infection. PARP inactivation reduced actin cytoskeleton rearrangements by affecting Rho GTPase machinery. These discoveries suggest that inactivation of PARP suppresses HIV replication in MDM by via attenuation of LTR activation, NFkappaB suppression and its effects on the cytoskeleton. PARP appears to be essential for HIV replication and its inhibition may provide an effective approach to management of HIV infection. PMID- 26379654 TI - Biocontrol agent Bacillus amyloliquefaciens LJ02 induces systemic resistance against cucurbits powdery mildew. AB - Powdery mildew is a fungal disease found in a wide range of plants and can significantly reduce crop yields. Bacterial strain LJ02 is a biocontrol agent (BCA) isolated from a greenhouse in Tianjin, China. In combination of morphological, physiological, biochemical and phylogenetic analyses, strain LJ02 was classified as a new member of Bacillus amyloliquefaciens. Greenhouse trials showed that LJ02 fermentation broth (LJ02FB) can effectively diminish the occurrence of cucurbits powdery mildew. When treated with LJ02FB, cucumber seedlings produced significantly elevated production of superoxide dismutase, peroxidase, polyphenol oxidase and phenylalanine ammonia lyase as compared to that of the control. We further confirmed that the production of free salicylic acid (SA) and expression of one pathogenesis-related (PR) gene PR-1 in cucumber leaves were markedly elevated after treating with LJ02FB, suggesting that SA mediated defense response was stimulated. Moreover, LJ02FB-treated cucumber leaves could secrete resistance-related substances into rhizosphere that inhibit the germination of fungi spores and the growth of pathogens. Finally, we separated bacterium and its fermented substances to test their respective effects and found that both components have SA-inducing activity and bacterium plays major roles. Altogether, we identified a BCA against powdery mildew and its mode of action by inducing systemic resistance such as SA signaling pathway. PMID- 26379655 TI - Histatin 5 inhibits adhesion of C. albicans to Reconstructed Human Oral Epithelium. AB - Candida albicans is the most pathogenic fungal species, commonly colonizing on human mucosal surfaces. As a polymorphic species, C. albicans is capable of switching between yeast and hyphal forms, causing an array of mucosal and disseminated infections with high mortality. While the yeast form is most commonly associated with systemic disease, the hyphae are more adept at adhering to and penetrating host tissue and are therefore frequently observed in mucosal fungal infections, most commonly oral candidiasis. The formation of a saliva derived protein pellicle on the mucosa surface can provide protection against C. albicans on oral epithelial cells, and narrow information is available on the mucosal pellicle composition. Histatins are one of the most abundant salivary proteins and presents antifungal and antibacterial activities against many species of the oral microbiota, however, its presence has never been studied in oral mucosa pellicle. The objective of this study was to evaluate the potential of histatin 5 to protect the Human Oral Epithelium against C. albicans adhesion. Human Oral Epithelial Tissues (HOET) were incubated with PBS containing histatin 5 for 2 h, followed by incubation with C. albicans for 1 h at 37 degrees C. The tissues were then washed several times in PBS, transferred to fresh RPMI and incubated for 16 h at 37 degrees C at 5% CO2. HOET were then prepared for histopathological analysis using light microscopy. In addition, the TUNEL assay was employed to evaluate the apoptosis of epithelial cells using fluorescent microscopy. HOET pre-incubated with histatin 5 showed a lower rate of C. albicans growth and cell apoptosis when compared to the control groups (HOET alone and HOET incubated with C. albicans). The data suggest that the coating with histatin 5 is able to reduce C. albicans colonization on epithelial cell surfaces and also protect the basal cell layers from undergoing apoptosis. PMID- 26379656 TI - Microbiome interplay: plants alter microbial abundance and diversity within the built environment. AB - The built indoor microbiome has importance for human health. Residents leave their microbial fingerprint but nothing is known about the transfer from plants. Our hypothesis that indoor plants contribute substantially to the microbial abundance and diversity in the built environment was experimentally confirmed as proof of principle by analyzing the microbiome of the spider plant Chlorophytum comosum in relation to their surroundings. The abundance of Archaea, Bacteria, and Eukaryota (fungi) increased on surrounding floor and wall surfaces within 6 months of plant isolation in a cleaned indoor environment, whereas the microbial abundance on plant leaves and indoor air remained stable. We observed a microbiome shift: the bacterial diversity on surfaces increased significantly but fungal diversity decreased. The majority of cells were intact at the time of samplings and thus most probably alive including diverse Archaea as yet unknown phyllosphere inhabitants. LEfSe and network analysis showed that most microbes were dispersed from plant leaves to the surrounding surfaces. This led to an increase of specific taxa including spore-forming fungi with potential allergic potential but also beneficial plant-associated bacteria, e.g., Paenibacillus. This study demonstrates for the first time that plants can alter the microbiome of a built environment, which supports the significance of plants and provides insights into the complex interplay of plants, microbiomes and human beings. PMID- 26379657 TI - Changes in primary metabolism under light and dark conditions in response to overproduction of a response regulator RpaA in the unicellular cyanobacterium Synechocystis sp. PCC 6803. AB - The study of the primary metabolism of cyanobacteria in response to light conditions is important for environmental biology because cyanobacteria are widely distributed among various ecological niches. Cyanobacteria uniquely possess circadian rhythms, with central oscillators consisting from three proteins, KaiA, KaiB, and KaiC. The two-component histidine kinase SasA/Hik8 and response regulator RpaA transduce the circadian signal from KaiABC to control gene expression. Here, we generated a strain overexpressing rpaA in a unicellular cyanobacterium Synechocystis sp. PCC 6803. The rpaA-overexpressing strain showed pleiotropic phenotypes, including slower growth, aberrant degradation of an RNA polymerase sigma factor SigE after the light-to-dark transition, and higher accumulation of sugar catabolic enzyme transcripts under dark conditions. Metabolome analysis revealed delayed glycogen degradation, decreased sugar phosphates and organic acids in the tricarboxylic acid cycle, and increased amino acids under dark conditions. The current results demonstrate that in this cyanobacterium, RpaA is a regulator of primary metabolism and involved in adaptation to changes in light conditions. PMID- 26379659 TI - The effect of human settlement on the abundance and community structure of ammonia oxidizers in tropical stream sediments. AB - Ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB) are a diverse and functionally important group in the nitrogen cycle. Nevertheless, AOA and AOB communities driving this process remain uncharacterized in tropical freshwater sediment. Here, the effect of human settlement on the AOA and AOB diversity and abundance have been assessed by phylogenetic and quantitative PCR analyses, using archaeal and bacterial amoA and 16S rRNA genes. Overall, each environment contained specific clades of amoA and 16S rRNA genes sequences, suggesting that selective pressures lead to AOA and AOB inhabiting distinct ecological niches. Human settlement activities, as derived from increased metal and mineral nitrogen contents, appear to cause a response among the AOB community, with Nitrosomonas taking advantage over Nitrosospira in impacted environments. We also observed a dominance of AOB over AOA in mining-impacted sediments, suggesting that AOB might be the primary drivers of ammonia oxidation in these sediments. In addition, ammonia concentrations demonstrated to be the driver for the abundance of AOA, with an inversely proportional correlation between them. Our findings also revealed the presence of novel ecotypes of Thaumarchaeota, such as those related to the obligate acidophilic Nitrosotalea devanaterra at ammonia-rich places of circumneutral pH. These data add significant new information regarding AOA and AOB from tropical freshwater sediments, albeit future studies would be required to provide additional insights into the niche differentiation among these microorganisms. PMID- 26379658 TI - Targeted metagenomics as a tool to tap into marine natural product diversity for the discovery and production of drug candidates. AB - Microbial natural products exhibit immense structural diversity and complexity and have captured the attention of researchers for several decades. They have been explored for a wide spectrum of applications, most noteworthy being their prominent role in medicine, and their versatility expands to application as drugs for many diseases. Accessing unexplored environments harboring unique microorganisms is expected to yield novel bioactive metabolites with distinguishing functionalities, which can be supplied to the starved pharmaceutical market. For this purpose the oceans have turned out to be an attractive and productive field. Owing to the enormous biodiversity of marine microorganisms, as well as the growing evidence that many metabolites previously isolated from marine invertebrates and algae are actually produced by their associated bacteria, the interest in marine microorganisms has intensified. Since the majority of the microorganisms are uncultured, metagenomic tools are required to exploit the untapped biochemistry. However, after years of employing metagenomics for marine drug discovery, new drugs are vastly under-represented. While a plethora of natural product biosynthetic genes and clusters are reported, only a minor number of potential therapeutic compounds have resulted through functional metagenomic screening. This review explores specific obstacles that have led to the low success rate. In addition to the typical problems encountered with traditional functional metagenomic-based screens for novel biocatalysts, there are enormous limitations which are particular to drug-like metabolites. We also present how targeted and function-guided strategies, employing modern, and multi-disciplinary approaches have yielded some of the most exciting discoveries attributed to uncultured marine bacteria. These discoveries set the stage for progressing the production of drug candidates from uncultured bacteria for pre clinical and clinical development. PMID- 26379661 TI - Evidence for Infection and Inflammation in Infant Deaths in a Country with Historically Low Incidences of Sudden Infant Death Syndrome. AB - Total infant mortality in Hungary has been higher than other European countries; however, the reported incidence of sudden infant death syndrome (SIDS) has been lower. The low incidence of SIDS in Hungary has been supported by evidence obtained from the high rate of scene of death investigation and medico-legal autopsy mandatory since the 1950s. In this study, we compared the incidence of explained and unexplained infant deaths in Hungary for three periods: 1979-1989 when the incidence of SIDS was high in western Europe; 1990-1999 when the incidence of infant deaths was falling following introduction of the public health campaigns to reduce the risk factors associated with SIDS; and 2000-2012 to determine if introduction of Haemophilus influenzae type b or pneumococcal vaccines or introduction of an earlier immunization schedule during this period had an effect on SIDS. Explained infant deaths fell consistently during this period; however, SIDS rose during the second period when the incidence of SIDS was falling in other European countries. Evidence for infection and/or inflammation was observed for the majority of SIDS during each period. The results are discussed in relation to campaigns to reduce infant mortality in Hungary and the introduction of new vaccines and an earlier immunization schedule in 2006. PMID- 26379660 TI - Cell aggregation promotes pyoverdine-dependent iron uptake and virulence in Pseudomonas aeruginosa. AB - In Pseudomonas aeruginosa the Gac signaling system and the second messenger cyclic diguanylate (c-di-GMP) participate in the control of the switch between planktonic and biofilm lifestyles, by regulating the production of the two exopolysaccharides Pel and Psl. The Gac and c-di-GMP regulatory networks also coordinately promote the production of the pyoverdine siderophore, and the extracellular polysaccharides Pel and Psl have recently been found to mediate c di-GMP-dependent regulation of pyoverdine genes. Here we demonstrate that Pel and Psl are also essential for Gac-mediated activation of pyoverdine production. A pel psl double mutant produces very low levels of pyoverdine and shows a marked reduction in the expression of the pyoverdine-dependent virulence factors exotoxin A and PrpL protease. While the exopolysaccharide-proficient parent strain forms multicellular planktonic aggregates in liquid cultures, the Pel and Psl-deficient mutant mainly grows as dispersed cells. Notably, artificially induced cell aggregation is able to restore pyoverdine-dependent gene expression in the pel psl mutant, in a way that appears to be independent of iron diffusion or siderophore signaling, as well as of recently described contact-dependent mechanosensitive systems. This study demonstrates that cell aggregation represents an important cue triggering the expression of pyoverdine-related genes in P. aeruginosa, suggesting a novel link between virulence gene expression, cell cell interaction and the multicellular community lifestyle. PMID- 26379662 TI - Prebiotic Supplementation has Only Minimal Effects on Growth Efficiency, Intestinal Health and Disease Resistance of Westslope Cutthroat Trout Oncorhynchus clarkii lewisi Fed 30% Soybean Meal. AB - Prebiotics have successfully been used to prevent infectious diseases in aquaculture and there is an increasing amount of literature that suggests that these products can also improve alternative protein utilization and digestion. Therefore, the objective of this study was to examine whether prebiotic supplementation increased the growth efficiency, intestinal health, and disease resistance of cutthroat trout fed a high level of dietary soybean meal. To achieve this objective, juvenile Westslope cutthroat trout (Oncorhynchus clarkii lewisi) were fed a practical type formulation with 0 or 30% dietary soybean meal with or without the commercial prebiotic (Grobiotic-A) prior to experimental exposure to Flavobacterium psychrophilum. Juvenile Westslope cutthroat trout (initial weight 7.8 g/fish +/-SD of 0.5 g) were stocked at 30 fish/tank in 75 L tanks with six replicate tanks per diet and fed their respective diets for 20 weeks. Final weights of Westslope cutthroat trout were affected by neither dietary soybean meal inclusion level (P = 0.9582) nor prebiotic inclusion (P = 0.9348) and no interaction was observed (P = 0.1242). Feed conversion ratios were similarly not affected by soybean meal level (P = 0.4895), prebiotic inclusion (P = 0.3258) or their interaction (P = 0.1478). Histological examination of the distal intestine of Westslope cutthroat trout demonstrated increases in inflammation due to both increased soybean meal inclusion level (P = 0.0038) and prebiotic inclusion (P = 0.0327) without significant interaction (P = 0.3370). Feeding dietary soybean meal level at 30% increased mortality of F. psychrophilum cohabitation challenged Westslope cutthroat trout (P = 0.0345) while prebiotic inclusion tended to decrease mortality (P = 0.0671). These results indicate that subclinical alterations in intestinal inflammation levels due to high dietary inclusion levels of soybean meal could predispose Westslope cutthroat trout to F. psychrophilum infection. PMID- 26379663 TI - Targeting C-Type Lectin Receptors for Cancer Immunity. AB - C-type lectin receptors (CLRs) are a large family of soluble and trans-membrane pattern recognition receptors that are widely and primarily expressed on myeloid cells. CLRs are important for cell-cell communication and host defense against pathogens through the recognition of specific carbohydrate structures. Similar to a family of Toll-like receptors, CLRs signaling are involved in the various steps for initiation of innate immune responses and promote secretion of soluble factors such as cytokines and interferons. Moreover, CLRs contribute to endocytosis and antigen presentation, thereby fine-tune adaptive immune responses. In addition, there may also be a direct activation of acquired immunity. On the other hand, glycans, such as mannose structures, Lewis-type antigens, or GalNAc are components of tumor antigens and ligate CLRs, leading to immunoregulation. Therefore, agonists or antagonists of CLRs signaling are potential therapeutic reagents for cancer immunotherapy. We aim to overview the current knowledge of CLRs signaling and the application of their ligands on tumor associating immune response. PMID- 26379664 TI - Immune Reactivation by Cell-Free Fetal DNA in Healthy Pregnancies Re-Purposed to Target Tumors: Novel Checkpoint Inhibition in Cancer Therapeutics. AB - The role of the immune system in cancer progression has become increasingly evident over the past decade. Chronic inflammation in the promotion of tumorigenesis is well established, and cancer-associated tolerance/immune evasion has long been appreciated. Recent developments of immunotherapies targeting cancer-associated inflammation and immune tolerance, such as cancer vaccines, cell therapies, neutralizing antibodies, and immune checkpoint inhibitors, have shown promising clinical results. However, despite significant therapeutic advances, most patients diagnosed with metastatic cancer still succumb to their malignancy. Treatments are often toxic, and the financial burden of novel therapies is significant. Thus, new methods for utilizing similar biological systems to compare complex biological processes can give us new hypotheses for combating cancer. One such approach is comparing trophoblastic growth and regulation to tumor invasion and immune escape. Novel concepts regarding immune activation in pregnancy, especially reactivation of the immune system at labor through toll like receptor engagement by fetal derived DNA, may be applicable to cancer immunotherapy. This review summarizes mechanisms of inflammation in cancer, current immunotherapies used in the clinic, and suggestions for looking beyond oncology for novel methods to reverse cancer-associated tolerance and immunologic exhaustion utilizing mechanisms encountered in normal human pregnancy. PMID- 26379666 TI - Characterization of the Antigen-Specific CD4(+) T Cell Response Induced by Prime Boost Strategies with CAF01 and CpG Adjuvants Administered by the Intranasal and Subcutaneous Routes. AB - The design of heterologous prime-boost vaccine combinations that optimally shape the immune response is of critical importance for the development of next generation vaccines. Here, we tested different prime-boost combinations using the tuberculosis vaccine antigen H56 with CAF01 or CpG ODN 1826 adjuvants, administered by the parenteral and nasal routes. Using peptide-MHC class II tetramers, antigen-specific CD4(+) T cells were tracked following primary and booster immunizations. Both parenteral priming with H56 plus CAF01 and nasal priming with H56 plus CpG elicited significant expansion of CD4(+) tetramer positive T cells in the spleen; however, only parenterally primed cells responded to booster immunization. Subcutaneous (SC) priming with H56 and CAF01 followed by nasal boosting with H56 and CpG showed the greater expansion of CD4(+) tetramer positive T cells in the spleen and lungs compared to all the other homologous and heterologous prime-boost combinations. Nasal boosting exerted a recruitment of primed CD4(+) T cells into lungs that was stronger in subcutaneously than nasally primed mice, in accordance with different chemokine receptor expression induced by primary immunization. These data demonstrate that SC priming is fundamental for eliciting CD4(+) T cells that can be efficiently boosted by the nasal route and results in the recruitment of antigen-experienced cells into the lungs. Combination of different vaccine formulations and routes of delivery for priming and boosting is a strategic approach for improving and directing vaccine-induced immune responses. PMID- 26379667 TI - Therapeutic Immunoglobulin Selected for High Antibody Titer to RSV also Contains High Antibody Titers to Other Respiratory Viruses. AB - Specific antibodies against infections most relevant to patients with primary immunodeficiency diseases are not routinely evaluated in commercial polyclonal immunoglobulin preparations. A polyclonal immunoglobulin prepared from plasma of donors having high neutralizing antibody titers to respiratory syncytial virus (RSV) was studied for the presence of antibody titers against seven additional respiratory viruses. While donors were not selected for antibody titers other than against RSV, the immunoglobulin preparation had significantly higher titers to 6 of 7 viruses compared to those present in 10 commercially available therapeutic immunoglobulin products (p <= 0.01 to p <= 0.001). To consider this as a donor-specific attribute, 20 random donor plasma samples were studied individually and identified a significant correlation between the RSV antibody titer and other respiratory virus titers: donors with high RSV titers were more likely to have higher titers to other respiratory viruses. These findings suggest either some humoral antiviral response bias or more frequent viral exposure of certain individuals. PMID- 26379665 TI - A Review of the Immunological Mechanisms Following Mucosal Vaccination of Finfish. AB - Mucosal organs are principle portals of entry for microbial invasion and as such developing protective vaccines against these pathogens can serve as a first line of defense against infections. In general, all mucosal organs in finfish are covered by a layer of mucus whose main function is not only to prevent pathogen attachment by being continuously secreted and sloughing-off but it serves as a vehicle for antimicrobial compounds, complement, and immunoglobulins that degrade, opsonize, and neutralize invading pathogens on mucosal surfaces. In addition, all mucosal organs in finfish possess antigen-presenting cells (APCs) that activate cells of the adaptive immune system to generate long-lasting protective immune responses. The functional activities of APCs are orchestrated by a vast array of proinflammatory cytokines and chemokines found in all mucosal organs. The adaptive immune system in mucosal organs is made of humoral immune responses that are able to neutralize invading pathogens as well as cellular mediated immune responses whose kinetics are comparable to those induced by parenteral vaccines. In general, finfish mucosal immune system has the capacity to serve as the first-line defense mechanism against microbial invasion as well as being responsive to vaccination. PMID- 26379668 TI - Multiplex Analysis of Serum Cytokines in Humans with Hantavirus Pulmonary Syndrome. AB - Hantavirus pulmonary syndrome (HPS) is an acute zoonotic disease transmitted primarily through inhalation of virus-contaminated aerosols. Hantavirus infection of endothelial cells leads to increased vascular permeability without a visible cytopathic effect. For this reason, it has been suggested that the pathogenesis of HPS is indirect with immune responses, such as cytokine production, playing a dominant role. In order to investigate their potential contribution to HPS pathogenesis, we analyzed the serum of hantavirus-infected subjects and healthy controls for 68 different cytokines, chemokines, angiogenic, and growth factors. Our analysis identified differential expression of cytokines that promote tissue migration of mononuclear cells including T lymphocytes, natural killer cells, and dendritic cells. Additionally, we observed a significant upregulation of cytokines known to regulate leukocyte migration and subsequent repair of lung tissue, as well as cytokines known to increase endothelial monolayer permeability and facilitate leukocyte transendothelial migration. Conversely, we observed a downregulation of cytokines associated with platelet numbers and function, consistent with the thrombocytopenia observed in subjects with HPS. This study corroborates clinical findings and extends our current knowledge regarding immunological and laboratory findings in subjects with HPS. PMID- 26379670 TI - Hypothetical Atopic Dermatitis-Myeloproliferative Neoplasm Syndrome. AB - Atopic dermatitis (AD) is a chronic inflammatory skin disease. Myeloproliferative neoplasms (MPNs) are hematopoietic malignancies caused by uncontrolled proliferation of hematopoietic stem/progenitor cells. Recent studies have described several mutant mice exhibiting both AD-like skin inflammation and MPN. Common pathways for skin inflammation encompass overexpression of thymic stromal lymphopoietin and reduced signaling of epidermal growth factor receptor in the epidermis, while overproduction of granulocyte-colony-stimulating factor by keratinocytes and constitutive activation of Stat5 in hematopoietic stem cells are important for the development of MPN. The murine studies suggest the existence of a similar human disease tentatively termed as the atopic dermatitis myeloproliferative neoplasm syndrome. PMID- 26379669 TI - Human Immunodeficiencies Related to Defective APC/T Cell Interaction. AB - The primary event for initiating adaptive immune responses is the encounter between T lymphocytes and antigen presenting cells (APCs) in the T cell area of secondary lymphoid organs and the formation of highly organized intercellular junctions referred to as immune synapses (IS). In vivo live-cell imaging of APC-T cell interactions combined to functional studies unveiled that T cell fate is dictated, in large part, by the stability of the initial contact. Immune cell interaction is equally important during delivery of T cell help to B cells and for the killing of target cells by cytotoxic T cells and NK cells. The critical role of contact dynamics and synapse stability on the immune response is well illustrated by human immune deficiencies in which disease pathogenesis is linked to altered adhesion or defective cross-talk between the synaptic partners. The Wiskott-Aldrich syndrome (WAS) is a severe primary immunodeficiency caused by mutations in the Wiskott-Aldrich syndrome protein (WASp), a scaffold that promotes actin polymerization and links TCR stimulation to T cell activation. Absence or mutations in WASp affects intercellular APC-T cell communications by interfering with multiple mechanisms on both sides of the IS. The warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome is caused by mutations in CXCR4, a chemokine receptor that in mutant form leads to impairment of APC-T cell interactions. Present evidences suggest that other recently characterized primary immune deficiencies caused by mutation in genes linked to actin cytoskeletal reorganization, such as WIP and DOCK8, may also depend on altered synapse stability. Here, we will discuss in details the mechanisms of disturbed APC-T cell interactions in WAS and WHIM. Moreover, we will summarize the evidence pointing to a compromised conjugate formation in WIP, DOCK8, and X linked lymphoproliferative syndrome. PMID- 26379671 TI - Editorial: Immunoglobulin Therapy in the 21st Century - the Dark Side of the Moon. PMID- 26379672 TI - An in silico Approach Reveals Associations between Genetic and Epigenetic Factors within Regulatory Elements in B Cells from Primary Sjogren's Syndrome Patients. AB - Recent advances in genetics have highlighted several regions and candidate genes associated with primary Sjogren's syndrome (SS), a systemic autoimmune epithelitis that combines exocrine gland dysfunctions, and focal lymphocytic infiltrations. In addition to genetic factors, it is now clear that epigenetic deregulations are present during SS and restricted to specific cell type subsets, such as lymphocytes and salivary gland epithelial cells. In this study, 72 single nucleotide polymorphisms (SNPs) associated with 43 SS gene risk factors were selected from publicly available and peer reviewed literature for further in silico analysis. SS risk variant location was tested revealing a broad distribution in coding sequences (5.6%), intronic sequences (55.6%), upstream/downstream genic regions (30.5%), and intergenic regions (8.3%). Moreover, a significant enrichment of regulatory motifs (promoter, enhancer, insulator, DNAse peak, and expression quantitative trait loci) characterizes SS risk variants (94.4%). Next, screening SNPs in high linkage disequilibrium (r (2) >= 0.8 in Caucasians) revealed 645 new variants including 5 SNPs with missense mutations, and indicated an enrichment of transcriptionally active motifs according to the cell type (B cells > monocytes > T cells ? A549). Finally, we looked at SS risk variants for histone markers in B cells (GM12878), monocytes (CD14(+)) and epithelial cells (A548). Active histone markers were associated with SS risk variants at both promoters and enhancers in B cells, and within enhancers in monocytes. In conclusion and based on the obtained in silico results that need further confirmation, associations were observed between SS genetic risk factors and epigenetic factors and these associations predominate in B cells, such as those observed at the FAM167A-BLK locus. PMID- 26379674 TI - The Role of Dipeptidyl Peptidase - 4 Inhibitors in Diabetic Kidney Disease. AB - Despite major advances in the understanding of the molecular mechanisms that underpin the development of diabetic kidney disease, current best practice still leaves a significant proportion of patients with end-stage kidney disease requiring renal replacement therapy. This is on a background of an increasing diabetes epidemic worldwide. Although kidney failure is a major cause of morbidity the main cause of death remains cardiovascular in nature. Hence, diabetic therapies which are both "cardio-renal" protective seem the logical way forward. In this review, we discuss the dipeptidyl peptidase 4 (DPP4) inhibitors (DPP4inh), which are glucose-lowering agents used clinically and their role in diabetic kidney disease with specific focus on renoprotection and surrogate markers of cardiovascular disease. We highlight the novel pleiotropic effects of DPP4 that make it an attractive additional target to combat the fibrotic and inflammatory pathways in diabetic kidney disease and also discuss the current literature on the cardiovascular safety profile of DPP4inh. Clearly, these observed renoprotective effects will need to be confirmed by clinical trials to determine whether they translate into beneficial effects to patients with diabetes. PMID- 26379675 TI - Commentary: "Can Selective MHC Downregulation Explain the Specificity and Genetic Diversity of NK Cell Receptors?". PMID- 26379673 TI - Regulatory T Cells: Serious Contenders in the Promise for Immunological Tolerance in Transplantation. AB - Regulatory T cells (Tregs) play an important role in immunoregulation and have been shown in animal models to promote transplantation tolerance and curb autoimmunity following their adoptive transfer. The safety and potential therapeutic efficacy of these cells has already been reported in Phase I trials of bone-marrow transplantation and type I diabetes, the success of which has motivated the broadened application of these cells in solid-organ transplantation. Despite major advances in the clinical translation of these cells, there are still key questions to be addressed to ensure that Tregs attest their reputation as ideal candidates for tolerance induction. In this review, we will discuss the unique traits of Tregs that have attracted such fame in the arena of tolerance induction. We will outline the protocols used for their ex vivo expansion and discuss the future directions of Treg cell therapy. In this regard, we will review the concept of Treg heterogeneity, the desire to isolate and expand a functionally superior Treg population and report on the effect of differing culture conditions. The relevance of Treg migratory capacity will also be discussed together with methods of in vivo visualization of the infused cells. Moreover, we will highlight key advances in the identification and expansion of antigen-specific Tregs and discuss their significance for cell therapy application. We will also summarize the clinical parameters that are of importance, alongside cell manufacture, from the choice of immunosuppression regimens to the number of injections in order to direct the success of future efficacy trials of Treg cell therapy. Years of research in the field of tolerance have seen an accumulation of knowledge and expertise in the field of Treg biology. This perpetual progression has been the driving force behind the many successes to date and has put us now within touching distance of our ultimate success, immunological tolerance. PMID- 26379676 TI - Arabidopsis PCNAs form complexes with selected D-type cyclins. AB - Proliferating Cell Nuclear Antigen (PCNA) is a key nuclear protein of eukaryotic cells. It has been shown to form complexes with cyclin dependent kinases, cyclin dependent kinase inhibitors and the D-type cyclins which are involved in the cell cycle control. In Arabidopsis two genes coding for PCNA1 and PCNA2 proteins have been identified. In this study by analyzing Arabidopsis PCNA/CycD complexes we tested the possible functional differentiation of PCNA1/2 proteins in cell cycle control. Most out of the 10 cyclins investigated showed only nuclear localization except CycD2;1, CycD4;1, and CycD4;2 which were observed both in the nucleus and cytoplasm. Using the Y2H, BiFC and FLIM-FRET techniques we identified D-type cyclins which formed complexes with either PCNA1 or PCNA2. Among the candidates tested only CycD1;1, CycD3;1, and CycD3;3 were not detected in a complex with the PCNA proteins. Moreover, our results indicate that the formation of CycD3;2/PCNA and CycD4;1/PCNA complexes can be regulated by other as yet unidentified factor(s). Additionally, FLIM-FRET analyses suggested that in planta the distance between PCNA1/CycD4;1, PCNA1/CycD6;1, PCNA1/CycD7;1, and PCNA2/CycD4;2 proteins was shorter than that between PCNA2/CycD4;1, PCNA2/CycD6;1, PCNA2/CycD7;1, and PCNA1/CycD4;2 pairs. These data indicate that the nine amino acid differences between PCNA1 and PCNA2 have an impact on the architecture of Arabidopsis CycD/PCNA complexes. PMID- 26379677 TI - An overview of methods using (13)C for improved compound identification in metabolomics and natural products. AB - Compound identification is a major bottleneck in metabolomics studies. In nuclear magnetic resonance (NMR) investigations, resonance overlap often hinders unambiguous database matching or de novo compound identification. In liquid chromatography-mass spectrometry (LC-MS), discriminating between biological signals and background artifacts and reliable determination of molecular formulae are not always straightforward. We have designed and implemented several NMR and LC-MS approaches that utilize (13)C, either enriched or at natural abundance, in metabolomics applications. For LC-MS applications, we describe a technique called isotopic ratio outlier analysis (IROA), which utilizes samples that are isotopically labeled with 5% (test) and 95% (control) (13)C. This labeling strategy leads to characteristic isotopic patterns that allow the differentiation of biological signals from artifacts and yield the exact number of carbons, significantly reducing possible molecular formulae. The relative abundance between the test and control samples for every IROA feature can be determined simply by integrating the peaks that arise from the 5 and 95% channels. For NMR applications, we describe two (13)C-based approaches. For samples at natural abundance, we have developed a workflow to obtain (13)C-(13)C and (13)C-(1)H statistical correlations using 1D (13)C and (1)H NMR spectra. For samples that can be isotopically labeled, we describe another NMR approach to obtain direct (13)C-(13)C spectroscopic correlations. These methods both provide extensive information about the carbon framework of compounds in the mixture for either database matching or de novo compound identification. We also discuss strategies in which (13)C NMR can be used to identify unknown compounds from IROA experiments. By combining technologies with the same samples, we can identify important biomarkers and corresponding metabolites of interest. PMID- 26379678 TI - Physio-biochemical and morphological characters of halophyte legume shrub, Acacia ampliceps seedlings in response to salt stress under greenhouse. AB - Acacia ampliceps (salt wattle), a leguminous shrub, has been introduced in salt affected areas in the northeast of Thailand for the remediation of saline soils. However, the defense mechanisms underlying salt tolerance A. ampliceps are unknown. We investigated various physio-biochemical and morphological attributes of A. ampliceps in response to varying levels of salt treatment (200-600 mM NaCl). Seedlings of A. ampliceps (25 +/- 2 cm in plant height) raised from seeds were treated with 200 mM (mild stress), 400 and 600 mM (extreme stress) of salt treatment (NaCl) under greenhouse conditions. Na(+) and Ca(2+) contents in the leaf tissues increased significantly under salt treatment, whereas K(+) content declined in salt-stressed plants. Free proline and soluble sugar contents in plants grown under extreme salt stress (600 mM NaCl) for 9 days significantly increased by 28.7 (53.33 MUmol g(-1) FW) and 3.2 (42.11 mg g(-1) DW) folds, respectively over the control, thereby playing a major role as osmotic adjustment. Na(+) enrichment in the phyllode tissues of salt-stressed seedlings positively related to total chlorophyll (TC) degradation (R (2) = 0.72). Photosynthetic pigments and chlorophyll fluorescence in salt-stressed plants increased under mild salt stress (200 mM NaCl). However, these declined under high levels of salinity (400-600 mM NaCl), consequently resulting in a reduced net photosynthetic rate (R (2) = 0.81) and plant dry weight (R (2) = 0.91). The study concludes that A. ampliceps has an osmotic adjustment and Na(+) compartmentation as effective salt defense mechanisms, and thus it could be an excellent species to grow in salt-affected soils. PMID- 26379679 TI - Ethylene responsive factors in the orchestration of stress responses in monocotyledonous plants. AB - The APETALA2/Ethylene-Responsive Factor (AP2/ERF) superfamily of transcription factors (TFs) regulates physiological, developmental and stress responses. Most of the AP2/ERF TFs belong to the ERF family in both dicotyledonous and monocotyledonous plants. ERFs are implicated in the responses to both biotic and abiotic stress and occasionally impart multiple stress tolerance. Studies have revealed that ERF gene function is conserved in dicots and monocots. Moreover, successful stress tolerance phenotypes are observed on expression in heterologous systems, making ERFs promising candidates for engineering stress tolerance in plants. In this review, we summarize the role of ERFs in general stress tolerance, including responses to biotic and abiotic stress factors, and endeavor to understand the cascade of ERF regulation resulting in successful signal-to response translation in monocotyledonous plants. PMID- 26379681 TI - Relaxed random walk model coupled with ecological niche modeling unravel the dispersal dynamics of a Neotropical savanna tree species in the deeper Quaternary. AB - Understanding the dispersal routes of Neotropical savanna tree species is an essential step to unravel the effects of past climate change on genetic patterns, species distribution and population demography. Here we reconstruct the demographic history and dispersal dynamics of the Neotropical savanna tree species Tabebuia aurea to understand the effects of Quaternary climate change on its current spatial patterns of genetic diversity. We sampled 285 individuals from 21 populations throughout Brazilian savannas and sequenced all individuals for three chloroplast intergenic spacers and ITS nrDNA. We analyzed data using a multi-model inference framework by coupling the relaxed random walk model (RRW), ecological niche modeling (ENM) and statistical phylogeography. The most recent common ancestor of T. aurea lineages dated from ~4.0 +/- 2.5 Ma. T. aurea lineages cyclically dispersed from the West toward the Central-West Brazil, and from the Southeast toward the East and Northeast Brazil, following the paleodistribution dynamics shown by the ENMs through the last glacial cycle. A historical refugium through time may have allowed dispersal of lineages among populations of Central Brazil, overlapping with population expansion during interglacial periods and the diversification of new lineages. Range and population expansion through the Quaternary were, respectively, the most frequent prediction from ENMs and the most likely demographic scenario from coalescent simulations. Consistent phylogeographic patterns among multiple modeling inferences indicate a promising approach, allowing us to understand how cyclical climate changes through the Quaternary drove complex population dynamics and the current patterns of species distribution and genetic diversity. PMID- 26379680 TI - Circadian regulation of abiotic stress tolerance in plants. AB - Extremes of temperatures, drought and salinity cause widespread crop losses throughout the world and impose severe limitations on the amount of land that can be used for agricultural purposes. Hence, there is an urgent need to develop crops that perform better under such abiotic stress conditions. Here, we discuss intriguing, recent evidence that circadian clock contributes to plants' ability to tolerate different types of environmental stress, and to acclimate to them. The clock controls expression of a large fraction of abiotic stress-responsive genes, as well as biosynthesis and signaling downstream of stress response hormones. Conversely, abiotic stress results in altered expression and differential splicing of the clock genes, leading to altered oscillations of downstream stress-response pathways. We propose a range of mechanisms by which this intimate coupling between the circadian clock and environmental stress response pathways may contribute to plant growth and survival under abiotic stress. PMID- 26379682 TI - The role of MYB34, MYB51 and MYB122 in the regulation of camalexin biosynthesis in Arabidopsis thaliana. AB - The phytoalexin camalexin and indolic glucosinolates share not only a common evolutionary origin and a tightly interconnected biosynthetic pathway, but regulatory proteins controlling the shared enzymatic steps are also modulated by the same R2R3-MYB transcription factors. The indolic phytoalexin camalexin is a crucial defense metabolite in the model plant Arabidopsis. Indolic phytoalexins and glucosinolates appear to have a common evolutionary origin and are interconnected on the biosynthetic level: a key intermediate in the biosynthesis of camalexin, indole-3-acetaldoxime (IAOx), is also required for the biosynthesis of indolic glucosinolates and is under tight control by the transcription factors MYB34, MYB51, and MYB122. The abundance of camalexin was strongly reduced in myb34/51 and myb51/122 double and in triple myb mutant, suggesting that these transcription factors are important in camalexin biosynthesis. Furthermore, expression of MYB51 and MYB122 was significantly increased by biotic and abiotic camalexin-inducing agents. Feeding of the triple myb34/51/122 mutant with IAOx or indole-3-acetonitrile largely restored camalexin biosynthesis. Conversely, tryptophan could not complement the low camalexin phenotype of this mutant, which supports a role for the three MYB factors in camalexin biosynthesis upstream of IAOx. Consistently expression of the camalexin biosynthesis genes CYP71B15/PAD3 and CYP71A13 was not negatively affected in the triple myb mutant and the MYBs could not activate pCYP71B15::uidA expression in trans-activation assays with cultured Arabidopsis cells. In conclusion, this study reveals the importance of MYB factors regulating the generation of IAOx as precursor of camalexin. PMID- 26379684 TI - Significance of galactinol and raffinose family oligosaccharide synthesis in plants. AB - Abiotic stress induces differential expression of genes responsible for the synthesis of raffinose family of oligosaccharides (RFOs) in plants. RFOs are described as the most widespread D-galactose containing oligosaccharides in higher plants. Biosynthesis of RFOs begin with the activity of galactinol synthase (GolS; EC 2.4.1.123), a GT8 family glycosyltransferase that galactosylates myo-inositol to produce galactinol. Raffinose and the subsequent higher molecular weight RFOs (Stachyose, Verbascose, and Ajugose) are synthesized from sucrose by the subsequent addition of activated galactose moieties donated by Galactinol. Interestingly, GolS, the key enzyme of this pathway is functional only in the flowering plants. It is thus assumed that RFO synthesis is a specialized metabolic event in higher plants; although it is not known whether lower plant groups synthesize any galactinol or RFOs. In higher plants, several functional importance of RFOs have been reported, e.g., RFOs protect the embryo from maturation associated desiccation, are predominant transport carbohydrates in some plant families, act as signaling molecule following pathogen attack and wounding and accumulate in vegetative tissues in response to a range of abiotic stresses. However, the loss-of-function mutants reported so far fail to show any perturbation in those biological functions. The role of RFOs in biotic and abiotic stress is therefore still in debate and their specificity and related components remains to be demonstrated. The present review discusses the biology and stress-linked regulation of this less studied extension of inositol metabolic pathway. PMID- 26379683 TI - Plant-derived immunomodulators: an insight on their preclinical evaluation and clinical trials. AB - The phagocyte-microbe interactions in the immune system is a defense mechanism but when excessively or inappropriately deployed can harm host tissues and participate in the development of different non-immune and immune chronic inflammatory diseases such as autoimmune problems, allergies, some rheumatoid disorders, cancers and others. Immunodrugs include organic synthetics, biological agents such as cytokines and antibodies acting on single targets or pathways have been used to treat immune-related diseases but with limited success. Most of immunostimulants and immunosuppressants in clinical use are the cytotoxic drugs which possess serious side effects. There is a growing interest to use herbal medicines as multi-component agents to modulate the complex immune system in the prevention of infections rather than treating the immune-related diseases. Many therapeutic effects of plant extracts have been suggested to be due to their wide array of immunomodulatory effects and influence on the immune system of the human body. Phytochemicals such as flavonoids, polysaccharides, lactones, alkaloids, diterpenoids and glycosides, present in several plants, have been reported to be responsible for the plants immunomodulating properties. Thus the search for natural products of plant origin as new leads for development of potent and safe immunosuppressant and immunostimulant agents is gaining much major research interest. The present review will give an overview of widely investigated plant derived compounds (curcumin, resveratrol, epigallocatechol-3-gallate, quercetin, colchicine, capsaicin, andrographolide, and genistein) which have exhibited potent effects on cellular and humoral immune functions in pre-clinical investigations and will highlight their clinical potential. PMID- 26379685 TI - A nitrogen source-dependent inducible and repressible gene expression system in the red alga Cyanidioschyzon merolae. AB - The unicellular red alga Cyanidioschyzon merolae is a model organism for studying the basic biology of photosynthetic organisms. The C. merolae cell is composed of an extremely simple set of organelles. The genome is completely sequenced. Gene targeting and a heat-shock inducible gene expression system has been recently established. However, a conditional gene knockdown system has not been established, which is required for the examination of function of genes that are essential to cell viability and primary mutant defects. In the current study, we first evaluated the expression of a transgene from two chromosomal neutral loci located in the intergenic region between CMD184C and CMD185C, and a region upstream of the URA5.3 gene. There was no significant difference in expression between them and this result suggests that both may be used as neutral loci. We then designed an inducible and repressible gene expression by using promoters of nitrate-assimilation genes. The expression of nitrate-assimilation genes such as NR (nitrate reductase), NIR (nitrite reductase), and NRT (the nitrate/nitrite transporter) are reversibly regulated by their dependence on nitrogen sources. We constructed stable strains in which a cassette containing the NR, NIR, or NRT promoter and sfGFP gene was inserted in a region upstream of URA5.3 and examined the efficacy of the promoters. The NR, NIR, and NRT promoters were constitutively activated in the nitrate medium, whereas their activities were extremely low in presence of ammonium. The activation of each promoter was immediately inhibited within a period of 1 h by the addition of ammonium. Thus, a conditional knockdown system in C. merolae was successfully established. The activity varies among the promoters, and each is selectable according to the expression level of a target gene estimated by RNA-sequencing. This method is applicable to defects in genes of interest in photosynthetic organism. PMID- 26379686 TI - Peroxisomes contribute to reactive oxygen species homeostasis and cell division induction in Arabidopsis protoplasts. AB - The ability to induce Arabidopsis protoplasts to dedifferentiate and divide provides a convenient system to analyze organelle dynamics in plant cells acquiring totipotency. Using peroxisome-targeted fluorescent proteins, we show that during protoplast culture, peroxisomes undergo massive proliferation and disperse uniformly around the cell before cell division. Peroxisome dispersion is influenced by the cytoskeleton, ensuring unbiased segregation during cell division. Considering their role in oxidative metabolism, we also investigated how peroxisomes influence homeostasis of reactive oxygen species (ROS). Protoplast isolation induces an oxidative burst, with mitochondria the likely major ROS producers. Subsequently ROS levels in protoplast cultures decline, correlating with the increase in peroxisomes, suggesting that peroxisome proliferation may also aid restoration of ROS homeostasis. Transcriptional profiling showed up-regulation of several peroxisome-localized antioxidant enzymes, most notably catalase (CAT). Analysis of antioxidant levels, CAT activity and CAT isoform 3 mutants (cat3) indicate that peroxisome-localized CAT plays a major role in restoring ROS homeostasis. Furthermore, protoplast cultures of pex11a, a peroxisome division mutant, and cat3 mutants show reduced induction of cell division. Taken together, the data indicate that peroxisome proliferation and CAT contribute to ROS homeostasis and subsequent protoplast division induction. PMID- 26379687 TI - Controlling weeds with fungi, bacteria and viruses: a review. AB - Weeds are a nuisance in a variety of land uses. The increasing prevalence of both herbicide resistant weeds and bans on cosmetic pesticide use has created a strong impetus to develop novel strategies for controlling weeds. The application of bacteria, fungi and viruses to achieving this goal has received increasingly great attention over the last three decades. Proposed benefits to this strategy include reduced environmental impact, increased target specificity, reduced development costs compared to conventional herbicides and the identification of novel herbicidal mechanisms. This review focuses on examples from North America. Among fungi, the prominent genera to receive attention as bioherbicide candidates include Colletotrichum, Phoma, and Sclerotinia. Among bacteria, Xanthomonas and Pseudomonas share this distinction. The available reports on the application of viruses to controlling weeds are also reviewed. Focus is given to the phytotoxic mechanisms associated with bioherbicide candidates. Achieving consistent suppression of weeds in field conditions is a common challenge to this control strategy, as the efficacy of a bioherbicide candidate is generally more sensitive to environmental variation than a conventional herbicide. Common themes and lessons emerging from the available literature in regard to this challenge are presented. Additionally, future directions for this crop protection strategy are suggested. PMID- 26379688 TI - Molecular dissection of Phaseolus vulgaris polygalacturonase-inhibiting protein 2 reveals the presence of hold/release domains affecting protein trafficking toward the cell wall. AB - The plant endomembrane system is massively involved in the synthesis, transport and secretion of cell wall polysaccharides and proteins; however, the molecular mechanisms underlying trafficking toward the apoplast are largely unknown. Besides constitutive, the existence of a regulated secretory pathway has been proposed. A polygalacturonase inhibitor protein (PGIP2), known to move as soluble cargo and reach the cell wall through a mechanism distinguishable from default, was dissected in its main functional domains (A, B, C, D), and C sub-fragments (C1-10), to identify signals essential for its regulated targeting. The secretion patterns of the fluorescent chimeras obtained by fusing different PGIP2 domains to the green fluorescent protein (GFP) were analyzed. PGIP2 N-terminal and leucine-rich repeat domains (B and C, respectively) seem to operate as holding/releasing signals, respectively, during PGIP2 transit through the Golgi. The B domain slows down PGIP2 secretion by transiently interacting with Golgi membranes. Its depletion leads, in fact, to the secretion via default (Sp2 susceptible) of the ACD-GFP chimera faster than PGIP2. Depending on its length (at least the first 5 leucine-rich repeats are required), the C domain modulates B interaction with Golgi membranes allowing the release of chimeras and their extracellular secretion through a Sp2 independent pathway. The addition of the vacuolar sorting determinant Chi to PGIP2 diverts the path of the protein from cell wall to vacuole, suggesting that C domain is a releasing rather than a cell wall sorting signal. PMID- 26379689 TI - Comparative analysis of complete chloroplast genome sequences of two tropical trees Machilus yunnanensis and Machilus balansae in the family Lauraceae. AB - Machilus is a large (c. 100 sp.) genus of trees in the family Lauraceae, distributed in tropical and subtropical East Asia. Both molecular species identification and phylogenetic studies of this morphologically uniform genus have been constrained by insufficient variable sites among frequently used biomarkers. To better understand the mutation patterns in the chloroplast genome of Machilus, the complete plastomes of two species were sequenced. The plastomes of Machilus yunnanensis and M. balansae were 152, 622 and 152, 721 bp, respectively. Seven highly variable regions between the two Machilus species were identified and 297 mutation events, including one micro-inversion in the ccsA ndhD region, 65 indels, and 231 substitutions, were accurately located. Thirty six microsatellite sites were found for use in species identification and 95 single-nucleotide changes were identified in gene coding regions. PMID- 26379690 TI - An engineered lipid remodeling system using a galactolipid synthase promoter during phosphate starvation enhances oil accumulation in plants. AB - Inorganic phosphate (Pi) depletion is a serious problem for plant growth. Membrane lipid remodeling is a defense mechanism that plants use to survive Pi depleted conditions. During Pi starvation, phospholipids are degraded to supply Pi for other essential biological processes, whereas galactolipid synthesis in plastids is up-regulated via the transcriptional activation of monogalactosyldiacylglycerol synthase 3 (MGD3). Thus, the produced galactolipids are transferred to extraplastidial membranes to substitute for phospholipids. We found that, Pi starvation induced oil accumulation in the vegetative tissues of various seed plants without activating the transcription of enzymes involved in the later steps of triacylglycerol (TAG) biosynthesis. Moreover, the Arabidopsis starchless phosphoglucomutase mutant, pgm-1, accumulated higher TAG levels than did wild-type plants under Pi-depleted conditions. We generated transgenic plants that expressed a key gene involved in TAG synthesis using the Pi deficiency responsive MGD3 promoter in wild-type and pgm-1 backgrounds. During Pi starvation, the transgenic plants accumulated higher TAG amounts compared with the non-transgenic plants, suggesting that the Pi deficiency-responsive promoter of galactolipid synthase in plastids may be useful for producing transgenic plants that accumulate more oil under Pi-depleted conditions. PMID- 26379691 TI - Intracellular delivery of fluorescent protein into viable wheat microspores using cationic peptides. AB - Microspores are specialized generative cells with haploid genome that demonstrate the amenability toward embryogenesis under certain conditions. The induced microspore culture technique is largely exploited by the breeding programs of wheat and other crops due to its high efficiency for generation of the large number of haploid plants in the relatively short period of time. The ability to produce mature double haploid plant from a single cell has also attracted attention of the plant biotechnologists in the past few years. More importantly, the possibility to deliver proteins for improvement of embryogenesis and the genome modification purposes holds great potential for transgene-free wheat biotechnology. In the present study, we examined the ability of cationic and amphipathic cell penetrating peptides (CPPs) to convey a covalently-linked mCherry protein inside the viable microspores. We demonstrate that the affinity of CPPs to the microspore cells dependents on their charge with the highest efficiency of CPP-mCherry binding to the cells achieved by cationic CPPs (penetratin and R9). Additionally, due to overall negative charge of the microspore cell wall, the successful uptake of the protein cargo by live microspore cells is attained by utilization of a reversible disulfide bond between the R9 CPP and mCherry protein. Overall, the approach proposed herein can be applied by the other biotechnology groups for the fast and efficient screening of the different CPP candidates for their ability to deliver proteins inside the viable plant cells. PMID- 26379692 TI - Limited DNA methylation variation and the transcription of MET1 and DDM1 in the genus Chrysanthemum (Asteraceae): following the track of polyploidy. AB - Polyploidy has been recognized as a widespread and common phenomenon among flowering plants. DNA-5'-CCGG site cytosine methylation (C-methylation) is one of the major and immediate epigenetic responses of the plant genome. Elucidating the ways in which altered C-methylation patterns, either at the whole genomic level or at specific sites can affect genome stability in polyploidy will require substantial additional investigation. Methylation sensitive amplification polymorphism profiling was used to evaluate variation in C-methylation among a set of 20 Chrysanthemum species and their close relatives of varying ploidy levels from diploid to decaploid. The range in relative C-methylation level was within 10%, and there was no significant difference neither between different ploidy levels nor between different species in the same ploidy level (U-values < 1.96). The transcript abundances of MET1 and DDM1 genes, which both involved in the regulation of C-methylation at CpG sites, were enhanced with increased ploidy level, but only MET1 was positively correlated with the nuclear DNA content. Considering the key role and efficiency of MET1 in maintaining CpG methylation, the limited variation observed with respect to C-methylation may reflect a balance between the increased activity of MET1 in the higher ploidy genomes and the larger number of CpG dinucleotide sites available for methylation. PMID- 26379693 TI - Comparative proteomic analysis of a membrane-enriched fraction from flag leaves reveals responses to chemical hybridization agent SQ-1 in wheat. AB - The induction of wheat male fertile lines by using the chemical hybridizing agent SQ-1 (CHA-SQ-1) is an effective approach in the utilization of heterosis; however, the molecular basis of male fertility remains unknown. Wheat flag leaves are the initial receptors of CHA-SQ-1 and their membrane structure plays a vital role in response to CHA-SQ-1 stress. To investigate the response of wheat flag leaves to CHA-SQ-1 stress, we compared their quantitative proteomic profiles in the absence and presence of CHA-SQ-1. Our results indicated that wheat flag leaves suffered oxidative stress during CHA-SQ-1 treatments. Leaf O2 (-), H2O2, and malonaldehyde levels were significantly increased within 10 h after CHA-SQ-1 treatment, while the activities of major antioxidant enzymes such as superoxide dismutase, catalase, and guaiacol peroxidase were significantly reduced. Proteome profiles of membrane-enriched fraction showed a change in the abundance of a battery of membrane proteins involved in multiple biological processes. These variable proteins mainly impaired photosynthesis, ATP synthesis protein mechanisms and were involved in the response to stress. These results provide an explanation of the relationships between membrane proteomes and anther abortion and the practical application of CHA for hybrid breeding. PMID- 26379695 TI - Biostimulants in agriculture. PMID- 26379694 TI - Identification of B6T173 (ZmPrx35) as the prevailing peroxidase in highly insect resistant maize (Zea mays, p84C3) kernels by activity-directed purification. AB - Plant peroxidases (PODs) are involved in diverse physiological processes, including defense against pathogens and insects. Contrary to their biological importance, only very few plant PODs have been proven on protein level, because their low abundance makes them difficult to detect in standard proteomics work flows. A statistically significant positive correlation between POD activity and post-harvest insect resistance has been found for maize (Zea mays, p84C3) kernels. In combining activity-directed protein purification, genomic and proteomic tools we found that protein B6T173 (ZmPrx35) is responsible for the majority of the POD activity of the kernel. We successfully produced recombinant ZmPrx35 protein in Escherichia coli and demonstrate both, in vitro activity and the presence of a haem (heme) cofactor of the enzyme. Our findings support the screening for insect resistant maize variants and the construction of genetically optimized maize plants. PMID- 26379696 TI - Characterization of protein N-glycosylation by tandem mass spectrometry using complementary fragmentation techniques. AB - The analysis of post-translational modifications (PTMs) by proteomics is regarded as a technically challenging undertaking. While in recent years approaches to examine and quantify protein phosphorylation have greatly improved, the analysis of many protein modifications, such as glycosylation, are still regarded as problematic. Limitations in the standard proteomics workflow, such as use of suboptimal peptide fragmentation methods, can significantly prevent the identification of glycopeptides. The current generation of tandem mass spectrometers has made available a variety of fragmentation options, many of which are becoming standard features on these instruments. We have used three common fragmentation techniques, namely CID, HCD, and ETD, to analyze a glycopeptide and highlight how an integrated fragmentation approach can be used to identify the modified residue and characterize the N-glycan on a peptide. PMID- 26379697 TI - Detecting modules in biological networks by edge weight clustering and entropy significance. AB - Detection of the modular structure of biological networks is of interest to researchers adopting a systems perspective for the analysis of omics data. Computational systems biology has provided a rich array of methods for network clustering. To date, the majority of approaches address this task through a network node classification based on topological or external quantifiable properties of network nodes. Conversely, numerical properties of network edges are underused, even though the information content which can be associated with network edges has augmented due to steady advances in molecular biology technology over the last decade. Properly accounting for network edges in the development of clustering approaches can become crucial to improve quantitative interpretation of omics data, finally resulting in more biologically plausible models. In this study, we present a novel technique for network module detection, named WG-Cluster (Weighted Graph CLUSTERing). WG-Cluster's notable features, compared to current approaches, lie in: (1) the simultaneous exploitation of network node and edge weights to improve the biological interpretability of the connected components detected, (2) the assessment of their statistical significance, and (3) the identification of emerging topological properties in the detected connected components. WG-Cluster utilizes three major steps: (i) an unsupervised version of k-means edge-based algorithm detects sub-graphs with similar edge weights, (ii) a fast-greedy algorithm detects connected components which are then scored and selected according to the statistical significance of their scores, and (iii) an analysis of the convolution between sub-graph mean edge weight and connected component score provides a summarizing view of the connected components. WG-Cluster can be applied to directed and undirected networks of different types of interacting entities and scales up to large omics data sets. Here, we show that WG-Cluster can be successfully used in the differential analysis of physical protein-protein interaction (PPI) networks. Specifically, applying WG-Cluster to a PPI network weighted by measurements of differential gene expression permits to explore the changes in network topology under two distinct (normal vs. tumor) conditions. WG-Cluster code is available at https://sites.google.com/site/paolaleccapersonalpage/. PMID- 26379698 TI - A porcine model system of BRCA1 driven breast cancer. AB - BRCA1 is a breast and ovarian tumor suppressor. Hereditary mutations in BRCA1 result in a predisposition to breast cancer, and BRCA1 expression is down regulated in ~30% of sporadic cases. The function of BRCA1 remains poorly understood, but it appears to play an important role in DNA repair and the maintenance of genetic stability. Mouse models of BRCA1 deficiency have been developed in an attempt to understand the role of the gene in vivo. However, the subtle nature of BRCA1 function and the well-known discrepancies between human and murine breast cancer biology and genetics may limit the utility of mouse systems in defining the function of BRCA1 in cancer and validating the development of novel therapeutics for breast cancer. In contrast to mice, pig biological systems, and cancer genetics appear to more closely resemble their human counterparts. To determine if BRCA1 inactivation in pig cells promotes their transformation and may serve as a model for the human disease, we developed an immortalized porcine breast cell line and stably inactivated BRCA1 using miRNA. The cell line developed characteristics of breast cancer stem cells and exhibited a transformed phenotype. These results validate the concept of using pigs as a model to study BRCA1 defects in breast cancer and establish the first porcine breast tumor cell line. PMID- 26379699 TI - Characterization of circulating transfer RNA-derived RNA fragments in cattle. AB - The objective was to characterize naturally occurring circulating transfer RNA derived RNA fragments (tRFs) in cattle. Serum from eight clinically normal adult dairy cows was collected, and small non-coding RNAs were extracted immediately after collection and sequenced by Illumina MiSeq. Sequences aligned to transfer RNA (tRNA) genes or their flanking sequences were characterized. Sequences aligned to the beginning of 5' end of the mature tRNA were classified as tRF5; those aligned to the 3' end of mature tRNA were classified as tRF3; and those aligned to the beginning of the 3' end flanking sequences were classified as tRF1. There were 3,190,962 sequences that mapped to transfer RNA and small non coding RNAs in the bovine genome. Of these, 2,323,520 were identified as tRF5s, 562 were tRF3s, and 81 were tRF1s. There were 866,799 sequences identified as other small non-coding RNAs (microRNA, rRNA, snoRNA, etc.) and were excluded from the study. The tRF5s ranged from 28 to 40 nucleotides; and 98.7% ranged from 30 to 34 nucleotides in length. The tRFs with the greatest number of sequences were derived from tRNA of histidine, glutamic acid, lysine, glycine, and valine. There was no association between number of codons for each amino acid and number of tRFs in the samples. The reason for tRF5s being the most abundant can only be explained if these sequences are associated with function within the animal. PMID- 26379700 TI - Evidence for the multiple hits genetic theory for inherited language impairment: a case study. AB - Communication disorders have complex genetic origins, with constellations of relevant gene markers that vary across individuals. Some genetic variants are present in healthy individuals as well as those affected by developmental disorders. Growing evidence suggests that some variants may increase susceptibility to these disorders in the presence of other pathogenic gene mutations. In the current study, we describe eight children with specific language impairment and four of these children had a copy number variant in one of these potential susceptibility regions on chromosome 15. Three of these four children also had variants in other genes previously associated with language impairment. Our data support the theory that 15q11.2 is a susceptibility region for developmental disorders, specifically language impairment. PMID- 26379701 TI - mRNA fragments in in vitro culture media are associated with bovine preimplantation embryonic development. AB - In vitro production (IVP) systems have been used to bypass problems of fertilization and early embryonic development. However, embryos produced by IVP are commonly selected for implantation based on morphological assessment, which is not a strong indicator of establishment and maintenance of pregnancy. Thus, there is a need to identify additional indicators of embryonic developmental potential. Previous studies have identified microRNA expression in in vitro culture media to be indicative of embryo quality in both bovine and human embryos. Like microRNAs, mRNAs have been shown to be secreted from cells into the extracellular environment, but it is unknown whether or not these RNAs are secreted by embryos. Thus, the objective of the present study was to determine whether mRNAs are secreted into in vitro culture media and if their expression in the media is indicative of embryo quality. In vitro culture medium was generated and collected from both blastocyst and degenerate (those which fail to develop from the morula to blastocyst stage) embryos. Small-RNA sequencing revealed that many mRNA fragments were present in the culture media. A total of 17 mRNA fragments were differentially expressed between blastocyst and degenerate conditioned media. Differential expression was confirmed by quantitative real time PCR for fragments of mRNA POSTN and VSNL-1, in four additional biological replicates of media. To better understand the mechanisms of mRNA secretion into the media, the expression of a predicted RNA binding protein of POSTN, PUM2, was knocked down using an antisense oligonucleotide gapmer. Supplementation of a PUM2 gapmer significantly reduced blastocyst development and decreased secretion of POSTN mRNA into the media. Overall, differential mRNA expression in the media was repeatable and sets the framework for future study of mRNA biomarkers in in vitro culture media to improve predictability of reproductive performance. PMID- 26379702 TI - Prolactin and growth hormone affect metaphase-II chromosomes in aging oocytes via cumulus cells using similar signaling pathways. AB - General senescence of the adult organism is closely connected with reproductive one. Meanwhile, the age-related reduction in the female fertility is primarily associated with a decline in the gamete quality. Molecular and cellular changes in oocytes of old mammalian females are very similar to those occurring during aging of matured ova of their young counterparts, suggesting similarities in underlying mechanisms. The aim of the present work was to study actions of two related pituitary hormones, prolactin (PRL) and growth hormone (GH), on age associated modifications of metaphase-II (M-II) chromosomes in bovine oocytes using a model of the prolonged culture. We analyzed: (1) effects of PRL and GH on abnormal changes in the chromosome morphology in aging matured oocytes and the role of cumulus cells in these effects and (2) signaling pathways involved in the hormone actions. During the prolonged culture of oocytes, a gradual rise in the frequency of destructive modifications of M-II chromosomes was revealed. In the case of cumulus-enclosed oocytes (CEOs), PRL and GH exerted dose-dependent biphasic effects on the frequency of these modifications. Both PRL (50 ng/ml) and GH (10 ng/ml) decelerated the abnormal chromosome changes in CEOs, but did not affect the chromosome configuration in denuded oocytes. Concurrently, the presence of PRL and GH receptors in cumulus cells surrounding matured oocytes was demonstrated. Attenuating effects of both hormones on the chromosome modifications in aging CEOs were abolished by PP2 (an inhibitor of Src-family tyrosine kinases), triciribine (an inhibitor of Akt kinase), and calphostin C (a protein kinase C inhibitor). Our findings indicate that PRL and GH can exert the similar decelerating action on age-associated alterations in the M-II chromosome morphology in bovine ova, which is mediated by cumulus cells and may be related to activation of Src-family tyrosine kinases as well as Akt- and protein kinase C dependent signal pathways. PMID- 26379703 TI - An Enhanced Differential Evolution with Elite Chaotic Local Search. AB - Differential evolution (DE) is a simple yet efficient evolutionary algorithm for real-world engineering problems. However, its search ability should be further enhanced to obtain better solutions when DE is applied to solve complex optimization problems. This paper presents an enhanced differential evolution with elite chaotic local search (DEECL). In DEECL, it utilizes a chaotic search strategy based on the heuristic information from the elite individuals to promote the exploitation power. Moreover, DEECL employs a simple and effective parameter adaptation mechanism to enhance the robustness. Experiments are conducted on a set of classical test functions. The experimental results show that DEECL is very competitive on the majority of the test functions. PMID- 26379704 TI - Provider Perspectives on the Influence of Family on Nursing Home Resident Transfers to the Emergency Department: Crises at the End of Life. AB - Background. Nursing home (NH) residents often experience burdensome and unnecessary care transitions, especially towards the end of life. This paper explores provider perspectives on the role that families play in the decision to transfer NH residents to the emergency department (ED). Methods. Multiple stakeholder focus groups (n = 35 participants) were conducted with NH nurses, NH physicians, nurse practitioners, physician assistants, NH administrators, ED nurses, ED physicians, and a hospitalist. Stakeholders described experiences and challenges with NH resident transfers to the ED. Focus group interviews were recorded and transcribed verbatim. Transcripts and field notes were analyzed using a Grounded Theory approach. Findings. Providers perceive that families often play a significant role in ED transfer decisions as they frequently react to a resident change of condition as a crisis. This sense of crisis is driven by 4 main influences: insecurities with NH care; families being unprepared for end of life; absent/inadequate advance care planning; and lack of communication and agreement within families regarding goals of care. Conclusions. Suboptimal communication and lack of access to appropriate and timely palliative care support and expertise in the NH setting may contribute to frequent ED transfers. PMID- 26379705 TI - Diagnosis and Treatment of Childhood Pulmonary Tuberculosis: A Cross-Sectional Study of Practices among Paediatricians in Private Sector, Mumbai. AB - Majority of children with tuberculosis are treated in private sector in India with no available data on management practices. The study assessed diagnostic and treatment practices related to childhood pulmonary tuberculosis among paediatricians in Mumbai's private sector in comparison with International Standards for Tuberculosis Care (ISTC) 2009. In this cross-sectional study, 64 paediatricians from private sector filled self-administered questionnaires. Cough was reported as a symptom of childhood TB by 77.8% of respondents. 38.1% request sputum smear or culture for diagnosis and fewer (32.8%) use it for patients positive on chest radiographs and 32.8% induce sputum for those unable to produce it. Sputum negative TB suspect is always tested with X-ray or tuberculin skin test. 61.4% prescribe regimen as recommended in ISTC and all monitor progress to treatment clinically. Drug-resistance at beginning of treatment is suspected for child in contact with a drug-resistant patient (67.7%) and with prior history of antitubercular treatment (12.9%). About half of them (48%) request drug resistance test for rifampicin in case of nonresponse after two to three months of therapy and regimen prescribed by 41.7% for multidrug-resistant TB was as per ISTC. The study highlights inappropriate diagnostic and treatment practices for managing childhood pulmonary TB among paediatricians in private sector. PMID- 26379706 TI - Comparison of Conventional Open Thyroidectomy and Endoscopic Thyroidectomy via Breast Approach for Papillary Thyroid Carcinoma. AB - Purpose. The aim of this study was to evaluate the feasibility of endoscopic thyroidectomy via breast approach for papillary thyroid carcinoma (PTC). Methods. Between March 2008 and March 2013, 34 patients with PTC received endoscopic thyroidectomy (endo group) and 30 patients received conventional open thyroidectomy (open group). Patients in two groups underwent ipsilateral central compartment node dissection. The two groups were compared in terms of patient characteristics, perioperative clinical results, and postoperative complication. Results. The rates of lymph node metastasis in endo group and open group were 23.5% (8/34) and 13.3% (4/30), respectively, without statistically significant difference (P = 0.351). The mean number of lymph nodes dissected was 2.4 +/- 2.9 in endoscopic group and 2.2 +/- 1.9 in open group (P = 0.774). During the follow up period, there was no recurrence or metastatic patients in two groups. All patients received the excellent cosmetic results in endo group, while 25 patients were satisfied with the cosmetic result and 5 were unsatisfied in the open group. Conclusions. The efficacy of endoscopic thyroidectomy via breast approach could be comparable to conventional open thyroidectomy in selected patients with PTC. PMID- 26379707 TI - Tumor-Associated Mast Cells in Thyroid Cancer. AB - There is compelling evidence that the tumor microenvironment plays a major role in mediating aggressive features of cancer cells, including invasive capacity and resistance to conventional and novel therapies. Among the different cell populations that infiltrate cancer stroma, mast cells (MCs) can influence several aspects of tumor biology, including tumor development and progression, angiogenesis, lymphangiogenesis, and tissue remodelling. Thyroid cancer (TC), the most frequent neoplasia of the endocrine system, is characterized by a MC infiltrate, whose density correlates with extrathyroidal extension and invasiveness. Recent evidence suggests the occurrence of epithelial-to mesenchymal transition (EMT) and stemness in human TC. The precise role of immune cells and their mediators responsible for these features in TC remains unknown. Here, we review the relevance of MC-derived mediators (e.g., the chemokines CXCL1/GRO-alpha, CXCL10/IP-10, and CXCL8/IL-8) in the context of TC. CXCL1/GRO alpha and CXCL10/IP-10 appear to be involved in the stimulation of cell proliferation, while CXCL8/IL-8 participates in the acquisition of TC malignant traits through its ability to induce/enhance the EMT and stem-like features of TC cells. The inhibition of chemokine signaling may offer novel therapeutic approaches for the treatment of refractory forms of TC. PMID- 26379708 TI - Investigation of Stilbenoids as Potential Therapeutic Agents for Rotavirus Gastroenteritis. AB - Rotavirus (RV) infections cause severe diarrhea in infants and young children worldwide. Vaccines are available but cost prohibitive for many countries and only reduce severe symptoms. Vaccinated infants continue to shed infectious particles, and studies show decreased efficacy of the RV vaccines in tropical and subtropical countries where they are needed most. Continuing surveillance for new RV strains, assessment of vaccine efficacy, and development of cost effective antiviral drugs remain an important aspect of RV studies. This study was to determine the efficacy of antioxidant and anti-inflammatory stilbenoids to inhibit RV replication. Peanut (A. hypogaea) hairy root cultures were induced to produce stilbenoids, which were purified by high performance countercurrent chromatography (HPCCC) and analyzed by HPLC. HT29.f8 cells were infected with RV in the presence stilbenoids. Cell viability counts showed no cytotoxic effects on HT29.f8 cells. Viral infectivity titers were calculated and comparatively assessed to determine the effects of stilbenoid treatments. Two stilbenoids, trans-arachidin-1 and trans-arachidin-3, show a significant decrease in RV infectivity titers. Western blot analyses performed on the infected cell lysates complemented the infectivity titrations and indicated a significant decrease in viral replication. These studies show the therapeutic potential of the stilbenoids against RV replication. PMID- 26379709 TI - Isolation of Fungi and Bacteria Associated with the Guts of Tropical Wood-Feeding Coleoptera and Determination of Their Lignocellulolytic Activities. AB - The guts of beetle larvae constitute a complex system where relationships among fungi, bacteria, and the insect host occur. In this study, we collected larvae of five families of wood-feeding Coleoptera in tropical forests of Costa Rica, isolated fungi and bacteria from their intestinal tracts, and determined the presence of five different pathways for lignocellulolytic activity. The fungal isolates were assigned to three phyla, 16 orders, 24 families, and 40 genera; Trichoderma was the most abundant genus, detected in all insect families and at all sites. The bacterial isolates were assigned to five phyla, 13 orders, 22 families, and 35 genera; Bacillus, Serratia, and Pseudomonas were the dominant genera, present in all the Coleopteran families. Positive results for activities related to degradation of wood components were determined in 65% and 48% of the fungal and bacterial genera, respectively. Our results showed that both the fungal and bacterial populations were highly diverse in terms of number of species and their phylogenetic composition, although the structure of the microbial communities varied with insect host family and the surrounding environment. The recurrent identification of some lignocellulolytic-positive inhabitants suggests that particular microbial groups play important roles in providing nutritional needs for the Coleopteran host. PMID- 26379710 TI - Ultrastructure of Placenta of Gravidas with Gestational Diabetes Mellitus. AB - Objectives. Gestational diabetes mellitus (GDM) leads to an abnormal placental environment which may cause some structural alterations of placenta and affect placental development and function. In this study, the ultrastructural appearances of term placentas from women with GDM and normal pregnancy were meticulously compared. Materials and Methods. The placenta tissues of term birth from 10 women with GDM and 10 women with normal pregnancy were applied with the signed informed consent. The morphology of fetomaternal interface of placenta was examined using light microscopy (LM) and transmission electron microscopy (TEM). Results. On LM, the following morphological changes in villous tissues were found in the GDM placentas when compared with the control placentas: edematous stroma, apparent increase in the number of syncytial knots, and perivillous fibrin deposition. On TEM, the distinct ultrastructural alterations indicating the degeneration of terminal villi were found in the GDM placentas as follows: thickening of the basal membrane (BM) of vasculosyncytial membrane (VSM) and the VSM itself, significantly fewer or even absent syncytiotrophoblastic microvilli, swollen or completely destroyed mitochondria and endoplasmic reticulum, and syncytiotrophoblasts with multiple vacuoles. Conclusion. Ultrastructural differences exist between GDM and control placentas. The differences of placenta ultrastructure are likely responsible for the impairment of placental barrier and function in GDM. PMID- 26379711 TI - Sinus of Valsalva Aneurysm: A Rare Cause of Dyspnea. AB - Sinus of Valsalva aneurysm (SOVA) is a rare clinical entity. Clinical manifestations can vary from an incidental finding on an imaging study to a life threatening emergency. We report a case of a 51-year-old female with a large symptomatic left SOVA. Echocardiogram and computed tomography angiography (CTA) of the chest revealed marked dilatation of the left sinus of Valsalva, measuring 7.5 cm. This resulted in superior displacement of the left main coronary artery. Surgical repair of the aneurysm with reimplantation of the right and left coronary arteries was performed in addition to aortic valve replacement (Bentall procedure). The patient had an uneventful postoperative course and remains asymptomatic at the three-month follow-up visit. PMID- 26379712 TI - Determinants of Adherence with Malaria Chemoprophylactic Drugs Used in a Traveler's Health Clinic. AB - Background. The WHO recommends mefloquine, atovaquone/proguanil, and doxycycline for malaria chemoprophylaxis. Adherence to a drug is determined by many factors. Objective. To detect the determinants of travelers' adherence to malaria chemoprophylaxis. Methods. A prospective comparative study was conducted from January 2012 to July 2013 that included travelers (928 travelers) to malaria endemic countries who visited the THC. They were classified into 3 groups: the 1st is the mefloquine group (396 travelers), the 2nd is the doxycycline group (370 travelers), and finally those who did not receive any drugs (162 travelers). The participants from the 1st and 2nd groups enrolled in the study. Results. Univariate and multivariate analyses were performed. The predictors for adherence in the mefloquine group were travel to an African destination [OR = 51 (6.8 2385)], higher than a secondary school education [OR = 21 (4.1-144.2)], organized travel [OR = 4 (2.1-6.5)], traveling for leisure [OR = 2.1 (1.1-0.4)], and nationality [OR = 2 (1.11-4.00)]. In the doxycycline group, the predictors included higher than a secondary education [OR = 20.1 (4.5-125.1)], organized travel [OR = 11.4 (5.5-20.9)], travel for leisure [OR = 7 (2.3-22.9)], travel to an African destination [OR = 6.1 (0.41-417)], and nationality [OR = 4.5 (2.3 9.5)]. Conclusion. Adherence with malaria chemoprophylaxis could be affected by many factors such as nationality, education, and organized travel. PMID- 26379713 TI - Clinicoradiological Profile of Lower Lung Field Tuberculosis Cases among Young Adult and Elderly People in a Teaching Hospital of Madhya Pradesh, India. AB - Aim. To study the clinical and radiological features of lower lung field tuberculosis (LLFTB) in relation to the patients of nonlower lung field tuberculosis (non-LLFTB). Material and Methods. All the patients of lower lung field tuberculosis defined by the lesions below an arbitrary line across the hila in their chest X-rays were included in the study. Their sputum for acid fast bacilli, HIV, blood sugar, and other relevant investigations were performed. Results. The total of 2136 cases of pulmonary tuberculosis was studied. Among them 215 (10%) cases of patients were diagnosed as the case of lower lung field tuberculosis. Females (62%) were more commonly affected. Most common clinical feature in non-LLFTB was cough (69%) followed by fever (65%), chest pain (54.7%), and weight loss (54.4%). Chest X-ray showed predominance of right side (60.9%) in cases of LLFTB. The relative risk of having the LLFTB in diabetes patients, HIV seropositive patients, end stage renal disease patients, and patients on corticosteroid therapy was high. Conclusion. Lower lung field tuberculosis is not an uncommon entity. It is more common in diabetes, HIV positive, end stage renal disease, and corticosteroid treated patients. Clinical and radiological features are different from upper lobe tuberculosis patients. PMID- 26379714 TI - Protective Effect of Aqueous Crude Extract of Neem (Azadirachta indica) Leaves on Plasmodium berghei-Induced Renal Damage in Mice. AB - Malaria is a major public health problem in the world because it can cause of death in patients. Malaria-associated renal injury is associated with 45% of mortality in adult patients hospitalized with severe form of the disease. Therefore, new plant extracts to protect against renal injury induced by malaria infection are urgently needed. In this study, we investigated the protective effect of aqueous crude extract of Azadirachta indica (neem) leaves on renal injury induced by Plasmodium berghei ANKA infection in mice. ICR mice were injected intraperitoneally with 1 * 10(7) parasitized erythrocytes of PbANKA, and neem extracts (500, 1,000, and 2,000 mg/kg) were given orally for 4 consecutive days. Plasma blood urea nitrogen (BUN) and creatinine levels were subsequently measured. Malaria-induced renal injury was evidenced as marked increases of BUN and creatinine levels. However, the oral administration of neem leaf extract to PbANKA infected mice for 4 days brought back BUN and creatinine levels to near normalcy, and the highest activity was observed at doses of 1,000 and 2,000 mg/kg. Additionally, no toxic effects were found in normal mice treated with this extract. Hence, neem leaf extract can be considered a potential candidate for protection against renal injury induced by malaria. PMID- 26379715 TI - Perceptions of Weight and Health Practices in Hispanic Children: A Mixed-Methods Study. AB - Background. Perception of weight by parents of obese children may be associated with willingness to engage in behavior change. The relationship between parents' perception of their child's weight and their health beliefs and practices is poorly understood, especially among the Hispanic population which experiences disparities in childhood obesity. This study sought to explore the relationship between perceptions of weight and health beliefs and practices in a Hispanic population. Methods. A cross-sectional, mixed-methods approach was used with semistructured interviews conducted with parent-child (2-5 years old) dyads in a primarily Hispanic, low-income population. Parents were queried on their perceptions of their child's health, health practices, activities, behaviors, and beliefs. A grounded theory approach was used to analyze participants' discussion of health practices and behaviors. Results. Forty parent-child dyads completed the interview. Most (58%) of the parents of overweight and obese children misclassified their child's weight status. The qualitative analysis showed that accurate perception of weight was associated with internal motivation and more concrete ideas of what healthy meant for their child. Conclusions. The qualitative data suggest there may be populations at different stages of readiness for change among parents of overweight and obese children, incorporating this understanding should be considered for interventions. PMID- 26379716 TI - The Social Determinants of Health in Military Forces of Iran: A Qualitative Study. AB - Providing effective health interventions and achieving equity in health need to apply the community-based approaches such as social determinants of health. In the military organizations, these determinants have received less attention from the military health researchers and policymakers. Therefore, this study aimed to identify and explain the social determinants affecting the health of military forces in Iran. This was a qualitative study which was conducted in 2014. The required data were collected through semistructured interviews and analyzed through Conventional Content Analysis. The studied sample consisted of 22 military health experts, policymakers, and senior managers selected using purposeful sampling method with maximum variation sampling. MAXQDA.2007 was used to analyze the collected data. After analyzing the collected data, two main contents, that is, "general social determinants of health" and "military social determinants of health," with 22 themes and 90 subthemes were identified as the social determinants of military forces' health. Main themes were religious rule, spirituality promotion policies, international military factors, military command, and so forth. Given the role and importance of social factors determining the military forces' health, it can be recommended that the military organizations should pay more attention to these determinants in making policies and creating social, economic, and cultural structures for their forces. PMID- 26379717 TI - Focal form of congenital hyperinsulinism clearly detectable by contrast-enhanced computed tomography imaging. AB - The focal form of congenital hyperinsulinism (CHI) is characterized by a cluster of abnormal insulin-oversecreting beta cells within a restricted area of the pancreas. Although identification of the focal lesion is very important in the management of CHI, it has been reported that imaging studies, including computed tomography (CT), magnetic resonance imaging (MRI) scans, or angiography, are not helpful in identifying the focal lesion. Currently, fluorine-18-L dihydroxyphenylalanine positron emission tomography ((18)F-DOPA PET) is believed to be the only imaging modality that can identify the focal lesions. In this report, however, we present a case of a 7-month-old girl with the focal form of CHI, caused by a loss-of-function mutation in the ABCC8 gene, whose lesion was clearly visible as a hyperenhancing nodule on contrast-enhanced CT and dynamic MRI imaging. PMID- 26379718 TI - Next Generation Sequencing and the Child and Youth Psychiatrist. PMID- 26379719 TI - A Voxel Based Morphometry Study of Brain Gray Matter Volumes in Juvenile Obsessive Compulsive Disorder. AB - INTRODUCTION: Adult patients with Obsessive Compulsive Disorder (OCD) have been shown to have gray matter (GM) volume differences from healthy controls in multiple regions - the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), medial frontal gyri (MFG), striatum, thalamus, and superior parietal lobule. However, there is paucity of data with regard to juvenile OCD. Hence, we examined GM volume differences between juvenile OCD patients and matched healthy controls using voxel based morphometry (VBM) with the above apriori regions of interest. METHOD: Fifteen right handed juvenile patients with OCD and age- sex- handedness- matched healthy controls were recruited after administering the Mini International Neuropsychiatric Interview-KID and the Children's Yale-Brown Obsessive Compulsive Scale, and scanned using a 3 Tesla magnetic resonance imaging scanner. VBM methodology was followed. RESULTS: In comparison with healthy controls, patients had significantly smaller GM volumes in left ACC. YBOCS total score (current) showed significant negative correlation with GM volumes in bilateral OFC, and left superior parietal lobule. CONCLUSION: These findings while reiterating the important role of the orbito-fronto-striatal circuitry, also implicate in the parietal lobe - especially the superior parietal lobule as an important structure involved in the pathogenesis of OCD. PMID- 26379720 TI - The Effect of Maternal Stress during Pregnancy on IQ and ADHD Symptomatology. AB - OBJECTIVE: Maternal stress during pregnancy (MSDP) has been linked to a decrease in Intelligence Quotient (IQ) in the general population. The purpose of this study is to first examine the association between MSDP and IQ in children with Attention-Deficit/Hyperactivity Disorder (ADHD) and second, to confirm, in a large sample, the link between MSDP and ADHD behavioral symptomatology. METHODS: Four hundred ten children diagnosed with ADHD, ages six to 12, were consecutively recruited from the ADHD clinic and day hospital at the Douglas Institute from 1999 to 2013. IQ was assessed using the WISC III and IV. Symptom severity was evaluated using the Child Behavior Checklist (CBCL) and Connor's Global Index for Parents (CGI-P) and Teachers (CGI-T). RESULTS: No significant effect of MSDP on full scale IQ was observed, but MSDP had a significant effect on CBCL and CGI scores. Elevated MSDP was significantly associated with increased CBCL internalizing scores (beta=4.2, p<.01), CBCL externalizing scores (beta=1.9, p=.04), CGI-P restless-impulsive scores (beta=2.6, p=.01), CGI-P emotional lability scores (beta=3.1, p=.02), and CGI-T restless-impulsive (beta=2.2, p=.05) and emotional lability (beta=3.4, p=.04) scores. MSDP increased the variance explained of ADHD symptomatology even after controlling for various factors (i.e. familial income, parental education, smoking and drinking during pregnancy, gender and age). CONCLUSION: The study demonstrates that in children with ADHD, MSDP does not have an impact on IQ but rather on ADHD symptomatology, highlighting the importance of potentially offering psychological and social support to mothers who experience stress during pregnancy. PMID- 26379722 TI - Increased Risk of Asthma in Children with ADHD: Role of Prematurity and Maternal Stress during Pregnancy. AB - OBJECTIVE: ADHD and asthma are prevalent conditions in childhood, with complex pathophysiology involving genetic-environmental interplay. The study objective is to examine the prevalence of asthma in our ADHD population and explore factors that may increase the risk of developing asthma in children with ADHD. METHODS: We retrospectively analyzed the presence of maternal stress during pregnancy and history of asthma in 201 children diagnosed with ADHD. RESULTS: Chi-square analysis indicated significant higher presence of asthma in our ADHD sample compared to Quebec children, chi(2)(1, N = 201) = 15.37, P<0.001. Only prematurity and stress during pregnancy significantly predicted asthma in a logistic regression model, chi(2)(2)=23.70, P<0.001, with odds ratios of 10.6 (95% CI: 2.8-39.5) and 3.2 (95% CI: 1.4-7.3), respectively. CONCLUSION: Children with ADHD have a higher prevalence of asthma than the general Quebec pediatric population. Children with ADHD born prematurely and/or those whose mothers experienced stress during pregnancy have a significantly increased risk of developing asthma. The study highlights the importance of potentially offering social and psychological support to mothers who experienced stress during pregnancy and/or are at risk of delivering prematurely. PMID- 26379721 TI - Mental Health Implications of Traumatic Brain Injury (TBI) in Children and Youth. AB - OBJECTIVE: Traumatic brain injury (TBI) is the most common cause of death and disability in children and adolescents. Psychopathology is an established risk factor for, and a frequent consequence of, TBI. This paper reviews the literature relating psychopathology and TBI. METHOD: Selective literature review. RESULTS: The risk of sustaining a TBI is increased by pre-existing psychopathology (particularly ADHD and aggression) and psychosocial adversity. Even among individuals with no psychopathology prior to the injury, TBI is frequently followed by mental illness especially ADHD, personality change, conduct disorder and, less frequently, by post-traumatic stress and anxiety disorders. The outcome of TBI can be partially predicted by pre-injury adjustment and injury severity, but less well by age at injury. Few individuals receive treatment for mental illness following TBI. CONCLUSION: TBI has substantial relevance to mental health professionals and their clinical practice. Available evidence, while limited, indicates that the risk for TBI in children and adolescents is increased in the presence of several, potentially treatable mental health conditions and that the outcome of TBI involves a range of mental health problems, many of which are treatable. Prevention and management efforts targeting psychiatric risks and outcomes are an urgent priority. Child and adolescent mental health professionals can play a critical role in the prevention and treatment of TBI through advocacy, education, policy development and clinical practice. PMID- 26379723 TI - Engaging Street-Involved Youth in Dialectical Behaviour Therapy: A Secondary Analysis. AB - OBJECTIVE: The objective of this secondary analysis was to identify factors associated with engagement of street-involved youth in a Dialectical Behavioural Therapy (DBT) intervention. METHODS: This was a cross-sectional correlational study. Youth were recruited from two agencies providing services to street involved youth in Canada. Mental health indicators were selected for this secondary analysis to gain a better understanding of characteristics that may account for levels of engagement. RESULTS: Three distinct groups of participants were identified in the data, a) youth who expressed intention to engage, but did not start DBT (n=16); b) youth who started DBT but subsequently dropped out (n=39); and c) youth who completed the DBT intervention (n=67). Youth who did engage in the DBT intervention demonstrated increased years of education; increased depressive symptoms and suicidality; and lower levels of resilience and self-esteem compared to youth participants who did not engage in the intervention. CONCLUSIONS: These findings indicate that it is possible to engage street-involved youth in a DBT intervention who exhibit a high degree of mental health challenges. Despite the growing literature describing the difficult psychological and interpersonal circumstances of street-involved youth, there remains limited research regarding the process of engaging these youth in service. PMID- 26379724 TI - Next Generation Sequencing and Health Technology Assessment in Autism Spectrum Disorder. AB - Next generation sequencing (NGS) is a new genome-based technology showing great promise in delineating the genetic basis of autism thus facilitating diagnosis and in the future, the selection of treatment. NGS can have a targeted use as well as provide clinically important findings from medically actionable variants regarding the risk of other disorders. As more is learned about the genomic basis of autism, the clinical utility of the risk information will increase. But at what cost? As the medical management that ensues from primary and secondary (incidental) findings grows, there will be increased pressure on sub-specialists with a longer and more circuitous pathway to care. This will result in higher costs to health care systems and to families. Health technology assessment is needed to measure the additional costs associated with NGS compared to standard care and to weigh these costs against additional health benefits. Well-designed data collection systems should be implemented early in clinical translation of this technology to enable assessment of clinical utility and cost-effectiveness and to generate high quality evidence to inform clinical and budget allocation decision-making. PMID- 26379725 TI - Three Reasons why Studying Hoarding in Children and Adolescents is Important. AB - Hoarding is traditionally considered a disorder of adulthood but hoarding symptoms often begin in childhood and adolescence. However, there is very little published research into hoarding in youth. As described in this commentary, the study of hoarding in childhood and adolescence is important because hoarding symptoms: 1) often begin in childhood and adolescence; 2) often are chronic and persist into adulthood; and, 3) are associated with a number of negative outcomes and sequelae. Research into hoarding in youth could help identify individuals at risk for chronic and persistent hoarding disorder as well as determine interventions to change their trajectories. Improved understanding of hoarding in children and adolescents could in turn help minimize the negative effect of hoarding on the affected individuals, their families and society. PMID- 26379726 TI - Persisting without Evidence is a Problem: Suicide Prevention and Other Well Intentioned Interventions. PMID- 26379728 TI - [Not Available]. PMID- 26379729 TI - A comparison of the risk factors of intrahepatic recurrence, early recurrencen, and multiple recurrences after resection for single nodular hepatocellular carcinoma. AB - BACKGROUNDS/AIMS: Intrahepatic recurrence is one of the most important causes of compromised prognosis after surgical resection of hepatocellular carcinoma (HCC). This retrospective study was designed to identify and compare the risks of recurrence, early recurrence and multiple recurrences in a single patient population. METHODS: A series of 92 consecutive patients, who received resection for single nodular HCC at our institute from January 2007 to December 2013, were enrolled in this study. The patients were divided into recurrent and non recurrent groups; the recurrent group was further divided into subgroups by applying two criteria: early and late recurrence (with a cutoff of 18 months), and single and multiple (>=2) recurrence. The potential risk factors were compared using univariate and multivariate analyses. The subgroup analysis was performed to determine the effects of different cut-off values on the analysis. RESULTS: 41 recurrences (44.6%) occurred during a mean follow-up of 42.4 months. The Child-Pugh score, and the portal vein invasion were found to be independent risk factors of recurrence, but differentiation was the only independent risk factor of early recurrence. The serum alpha-fetoprotein, tumor size, tumor necrosis, and hemorrhage were found to be the risk factors of multiple recurrences according to the univariate analysis, but lacked significance according to the multivariate analysis. When the cutoffs for early and multiple recurrences were changed to <=10 months and >3 nodules, respectively, different risk factors were identified. CONCLUSIONS: Our results implicated that different factors can predict the recurrence, timing, and multiplicity of an HCC recurrence. Further studies should be conducted to prove the complex relationships between tumor burden, invasiveness, and underlying liver cirrhosis for initial tumors, and the timing and multiplicity of recurrent HCC. PMID- 26379730 TI - Hepatectomy, combined with intraoperative radiofrequency ablation in patients with multiple hepatocellular carcinomas. AB - BACKGROUNDS/AIMS: We compared the efficacy and safety of a hepatectomy, combined with intraoperative radiofrequency ablation to those of wider extent hepatectomy, alone, in patients with multiple hepatocellular carcinomas (HCCs). METHODS: Between January 2004 and December 2013, 78 patients with multiple HCCs underwent surgery. 25 patients were treated by hepatectomy, combined with intraoperative radiofrequency ablation (RFA) (group A), and 53 underwent hepatectomy only (group B). We retrospectively analyzed medical records to compare the clinical features of these two groups. RESULTS: Patients in group A had more limited resections (less than 2 segments) than those in group B (p<0.001). Patients in group A also tended to have fewer red blood cell transfusions than those in group B (p=0.060). Liver function- and surgery-related complications occurred only in group B. There were no in-hospital mortalities in both groups. The overall survival and disease free survival outcomes were not significantly different between groups A and B (p=0.177 and p=0.305, respectively). CONCLUSIONS: Hepatectomy combined with intraoperative RFA could be a safe and effective treatment option for patients with multiple HCCs, comparable to extended hepatectomy alone. PMID- 26379731 TI - Comparison between operative versus non-operative management of traumatic liver injury. AB - BACKGROUNDS/AIMS: The aim of this study was to compare operative versus non operative management of patients with liver injury and to ascertain the differences of the clinical features. METHODS: From April 2000 to July 2012, 191 patients were admitted to Seoul St. Mary's Hospital and St. Vincent's Hospital for liver injuries. Of these, 148 patients were included in this study. All patients were diagnosed using computed tomography (CT). The liver injury was graded in accordance with the American Association for the Surgery of Trauma liver injury scoring scale. Patients were divided into two groups: those who underwent surgery and those treated with non-operative management (NOM). There was a comparison between these two groups concerning the clinical characteristics, grade of liver injury, hemodynamic stability, laboratory findings, and mortality. RESULTS: According to the 148 patient records evaluated, 108 (72.9%) patients were treated with NOM, and 40 (27.1%) underwent surgery. Patients treated with NOM had significantly fewer severe injuries as rated using the Revised Traumatic Injury Scale, Injury Severity Score, and Glasgow Coma Scale. Grade of liver injury and number of patients with extravasation of contrast dye on CT and hemoperitoneum were higher in the operative group than in the NOM group. There were significant differences between the two groups for: heart rate, respiratory rate, systolic blood pressure, and mean hemoglobin levels at admission and after 4 hours. The operative group experienced a significantly higher mortality than the NOM group. CONCLUSIONS: The results of our study suggest that hemodynamic stability and the following should be considered for deciding the treatment for liver injuries: grade of liver injury, amount of blood loss, and injury scales scores. PMID- 26379732 TI - Feasibility and safety of day-surgery laparoscopic cholecystectomy: a single institution 5-year experience of 1140 cases. AB - BACKGROUNDS/AIMS: We report our experience with day-surgery laparoscopic cholecystectomy and assess its feasibility and safety. METHODS: Data was collected on all the patients who underwent day-surgery laparoscopic cholecystectomy between February 2009 and February 2014 at Prince Sultan Military Medical City, Riyadh, Kingdom of Saudi Arabia. All patients had symptomatic cholelithiasis that was proven on imaging studies with clearance of the common bile duct. The patient biographical data (age, gender, American Society of Anaesthesiology status, medical comorbidities) and surgical outcomes were then obtained. There was an evaluation of the success rate of day-surgery laparoscopic cholecystectomy, reasons for unexpected admission, and the re-admission rate. RESULTS: A total of 1,140 patients were included in this study. The success rate for day-surgery laparoscopic cholecystectomy was 96%. The reasons for unexpected hospital admission for 46 patients (4%) included persistent abdominal pain and postoperative emesis. The postoperative re-admission rate was 0.4% (5 patients). There were no major complications, and the conversion rate was 0.5% (6 patients). CONCLUSIONS: We suggest that day-surgery laparoscopic cholecystectomy is both safe and feasible in a local setting. Careful patient selection is essential in ensuring a high success rate. PMID- 26379733 TI - Branch duct intraductal papillary mucinous neoplasm of the pancreas: single center experience with 324 patients who underwent surgical resection. AB - BACKGROUNDS/AIMS: International treatment guidelines for branch duct intraductal papillary mucinous neoplasm (BD-IPMN) of the pancreas have been proposed, for features associated with malignancy and invasiveness. We investigated the clinicopathological characteristics that are predictive of malignancy or invasiveness and disease recurrence. METHODS: A review of 324 patients with resected and pathologically confirmed BD-IPMN, between March 1997 and December 2013, was conducted. RESULTS: There were 144 (44.4%) low grade dysplasia (LGD), 138 (42.6%) intermediate grade dysplasia (IMGD), 17 (5.3%) high grade dysplasia (HGD), and 25 (7.7%) invasive carcinoma (invIPMC) cases. The 5-year survival rates were 98.1% for LGD, 95.3% for IMGD, 100% for HGD, and 71.8% for invIPMC. Through a univariate analysis, the male sex was associated with malignancy, and CA19-9 was related to both malignant and invasive IPMN. The high risk or worrisome features of the international guidelines were associated with both malignant and invasive IPMN: the total bilirubin of the head/uncinate lesion, tumor size, mural nodule, and the size of the main pancreatic duct (MPD). Through a multivariate analysis, the male sex, elevated CA19-9, mural nodule, and dilated MPD diameter were independently correlated with the malignant IPMN. The elevated CA19-9 and dilated MPD diameter were also correlated with invasive carcinoma. The patient age and the initial pathological diagnosis were strongly associated with disease recurrence following surgical resection. CONCLUSIONS: The high risk or worrisome features in the current treatment guidelines for BD-IPMN are confined to the morphological characteristics of the disease. Patient factors and biological features should also be considered in order to develop optimal therapeutic or surveillance strategies. PMID- 26379734 TI - A case of gallbladder cancer combined with ectopic individual opening of pancreatic and bile ducts to the duodenal bulb. AB - Ectopic opening of the pancreatic and bile ducts (EOPBD) into the duodenal bulb is an extremely rare congenital anomaly with unknown clinical implications. We presented a case of gallbladder cancer with EOPBD into the duodenal bulb. A 57 year-old male was referred to our hospital with intermittent right upper abdominal pain. Endoscopic retrograde cholangiopancreatography and magnetic resonance cholangiopancreatography showed individual EOPBD into the duodenal bulb with no papillary structure, and a focal nodular lesion in the gallbladder. A follow-up abdominal computed tomography scan 9 months later revealed a slight increase in the size of the fundal nodule, which was suspected as gallbladder cancer. An intraoperative frozen biopsy identified the nodular lesion as adenocarcinoma involving the cystic duct, and the patient underwent radical cholecystectomy including bile duct resection with hepaticojejunostomy. EOPBD is an extremely rare condition that can be associated with gallbladder malignancy as well as benign disease. Clinicians should follow up carefully and consider surgical treatment for suspected malignant lesions. PMID- 26379735 TI - Metastatic mucinous adenocarcinoma of the distal common bile duct, from transverse colon cancer presenting as obstructive jaundice. AB - The patient was a 70-year-old male whose chief complaints were obstructive jaundice and weight loss. Abdominal imaging studies showed a 2.5 cm sized mass at the distal common bile duct, which was suggestive of bile duct cancer. Eccentric enhancing wall thickening in the transverse colon was also shown, suggesting concomitant colon cancer. A colonoscopy revealed a lumen-encircling ulcerofungating mass in the transverse colon, that was pathologically proven to be adenocarcinoma. The bile duct pathology was also adenocarcinoma. Pylorus preserving pancreaticoduodenectomy and extended right hemicolectomy were performed under the diagnosis of double primary cancers. Postoperative histopathologic examination revealed moderately differentiated mucinous adenocarcinoma of transverse colon cancer, and mucinous adenocarcinoma of the distal common bile duct. Immunohistochemical staining studies showed that the bile duct cancer had metastasized from the colon cancer. The patient recovered uneventfully from surgery and will be undergoing chemotherapy for three months. PMID- 26379736 TI - Lymphoepithelial cyst of the pancreas mimicking malignant cystic tumor: report of a case. AB - Lymphoepithelial cysts of the pancreas are a type of true cyst that can mimic pseudocysts and cystic neoplasms. They are very rare, non-malignant lesions that are unilocular or multilocular cystic lesions lined predominantly by mature squamous epithelium and surrounded by non-neoplastic lymphoid elements. We, herein, present a patient with a cystic pancreas tumor mimicking a malignant cystic neoplasm. The patient was admitted with upper abdominal discomfort. Computed tomography showed a 64*39 mm cystic mass in the pancreas tail. She underwent distal pancreatectomy and splenectomy. In the fluid analysis of the pancreas cystic mass, the CEA and CA19-9 were 618 ng/ml and 3.9 U/ml, respectively. The resected pancreas specimen showed a 6.5 cm-sized cyst the pancreas tail. The cyst was well circumscribed and multilocular. The final pathology report of the resected pancreas specimen noted that the cyst was multilocular, and the cyst lining was showing stratified squamous epithelium covering the lymphoid tissue (containing lymphoid follicles), which was consistent with a lymphoepithelial cyst. The patient recovered uneventfully from surgery and has been doing well for the past 3 months. A differential diagnosis of cystic pancreatic lesions is important. We suggest that lymphoepithelial cysts, although very rare, may be included in the differential diagnosis of cystic pancreatic tumors. PMID- 26379737 TI - New Developments in the Primo Vascular System: Imaging and Functions with regard to Acupuncture. PMID- 26379738 TI - Effects of the Pinggan Qianyang Recipe on MicroRNA Gene Expression in the Aortic Tissue of Spontaneously Hypertensive Rats. AB - The present study aimed to investigate the relationship between miRNAs and in spontaneously hypertensive rats (SHR) vascular remodeling and analyze the impact of the Pinggan Qianyang recipe (PQR) on miRNAs. Mammalian miRNA microarrays containing 509 miRNA genes were employed to analyze the differentially expressed miRNAs in the three groups. MiRNAs were considered to be up- or downregulated when the fluorescent intensity ratio between the two groups was over 4-fold. Validation of those miRNAs changed in SHR after PQR treatment was used by real time quantitative RT-PCR (qRT-PCR). Compared with the normal group, a total of 32 miRNAs were differentially expressed by more than twofold; among these, 18 were upregulated and 14 were downregulated in the model group. Compared with the normal group, there were a number of 17 miRNAs which were significantly expressed by more than twofold in the different expressions of 32 miRNAs; among these, 10 were downregulated and 7 were upregulated in the PQR group. qRT-PCR verified that miR-20a, miR-145, miR-30, and miR-98 were significantly expressed in the three groups. These data show that PQR could exert its antihypertensive effect through deterioration of the vascular remodeling process. The mechanism might be associated with regulating differentially expressed miRNAs in aorta tissue. PMID- 26379739 TI - Antrodia camphorata Potentiates Neuroprotection against Cerebral Ischemia in Rats via Downregulation of iNOS/HO-1/Bax and Activated Caspase-3 and Inhibition of Hydroxyl Radical Formation. AB - Antrodia camphorata (A. camphorata) is a fungus generally used in Chinese folk medicine for treatment of viral hepatitis and cancer. Our previous study found A. camphorata has neuroprotective properties and could reduce stroke injury in cerebral ischemia animal models. In this study, we sought to investigate the molecular mechanisms of neuroprotective effects of A. camphorata in middle cerebral artery occlusion (MCAO) rats. A selective occlusion of the middle cerebral artery (MCA) with whole blood clots was used to induce ischemic stroke in rats and they were orally treated with A. camphorata (0.25 and 0.75 g/kg/day) alone or combined with aspirin (5 mg/kg/day). To provide insight into the functions of A. camphorata mediated neuroprotection, the expression of Bax, inducible nitric oxide synthase (iNOS), haem oxygenase-1 (HO-1), and activated caspase-3 was determined by Western blot assay. Treatment of aspirin alone significantly reduced the expressions of HO-1 (P < 0.001), iNOS (P < 0.001), and Bax (P < 0.01) in ischemic regions. The reduction of these expressions was more potentiated when rats treated by aspirin combined with A. camphorata (0.75 g/kg/day). Combination treatment also reduced apoptosis as measured by a significant reduction in active caspase-3 expression in the ischemic brain compared to MCAO group (P < 0.01). Moreover, treatment of A. camphorata significantly (P < 0.05) reduced fenton reaction-induced hydroxyl radical (OH(*)) formation at a dose of 40 mg/mL. Taken together, A. camphorata has shown neuroprotective effects in embolic rats, and the molecular mechanisms may correlate with the downregulation of Bax, iNOS, HO-1, and activated caspase-3 and the inhibition of OH(*) signals. PMID- 26379740 TI - Keishibukuryogan, a Traditional Japanese Medicine, Inhibits Platelet Aggregation in Guinea Pig Whole Blood. AB - Effects of keishibukuryogan (KBG) on platelet aggregation were investigated. To ensure the specificity of KBG, tokishakuyakusan (TSS) and kamisyoyosan (KSS), which are known to have platelet aggregation-inhibiting effects, and rikkunshito (RKT) and shakuyakukanzoto (SKT), which are considered to be devoid of such effects, were used for comparison. The platelet aggregation of each test drug was measured by the screen filtration pressure method using whole blood of guinea pigs and expressed as a collagen-induced pressure rate (%) or a collagen concentration required for 50% increase in the pressure rate (PATI value). KBG suppressed the collagen-induced whole blood pressure rate increase and increased the PATI value, like TSS and KSS. Neither RKT nor SKT showed these effects. The Moutan cortex and Cinnamomi cortex, the constituent crude drugs of KBG, showed KBG-like pressure rate suppression and PATI-increasing effects. Furthermore, paeonol, a representative component of Moutan cortex, and aspirin which is known to have platelet aggregation-inhibiting activity (COX-1 inhibitor) also showed similar effects. These results suggest that the platelet aggregation-inhibiting activity of the constituent crude drugs Moutan cortex and Cinnamomi cortex is involved in the improving effects of KBG on impaired microcirculation and that paeonol plays a role in these effects. PMID- 26379741 TI - Fascia and Primo Vascular System. AB - The anatomical basis for the concept of acupuncture points/meridians in traditional Chinese medicine (TCM) has not been resolved. This paper reviews the fascia research progress and the relationship among acupuncture points/meridians, primo vascular system (PVS), and fascia. Fascia is as a covering, with common origins of layers of the fascial system despite diverse names for individual parts. Fascia assists gliding and fluid flow and holds memory and is highly innervated. Fascia is intimately involved with nourishment of all cells of the body, including those of disease and cancer. The human body's fascia network may be the physical substrate represented by the meridians of TCM. The PVS is a newly found circulatory system; recent increased interest has led to new research and new discoveries in the anatomical and functional aspects of the PVS. The fasciology theory provides new insights into the physiological effects of acupuncture needling on basic cellular mechanisms including connective tissue mechanotransduction and regeneration. This view represents a theoretical basis and means for applying modern biomedical research to examining TCM principles and therapies, and it favors a holistic approach to diagnosis and treatment. PMID- 26379742 TI - Bioactives and Traditional Herbal Medicine for the Treatment of Cardiovascular/Cerebrovascular Diseases 2015. PMID- 26379743 TI - Primo-Vascular System as Presented by Bong Han Kim. AB - In the 1960s Bong Han Kim discovered and characterized a new vascular system. He was able to differentiate it clearly from vascular blood and lymph systems by the use of a variety of methods, which were available to him in the mid-20th century. He gave detailed characterization of the system and created comprehensive diagrams and photographs in his publications. He demonstrated that this system is composed of nodes and vessels, and it was responsible for tissue regeneration. However, he did not disclose in detail his methods. Consequently, his results are relatively obscure from the vantage point of contemporary scientists. The stains that Kim used had been perfected and had been in use for more than 100 years. Therefore, the names of the stains were directed to the explicit protocols for the usage with the particular cells or molecules. Traditionally, it was not normally necessary to describe the method used unless it is significantly deviated from the original method. In this present work, we have been able to disclose staining methods used by Kim. PMID- 26379744 TI - Effects of Tetramethylpyrazine on Functional Recovery and Neuronal Dendritic Plasticity after Experimental Stroke. AB - The 2,3,5,6-tetramethylpyrazine (TMP) has been widely used in the treatment of ischemic stroke by Chinese doctors. Here, we report the effects of TMP on functional recovery and dendritic plasticity after ischemic stroke. A classical model of middle cerebral artery occlusion (MCAO) was established in this study. The rats were assigned into 3 groups: sham group (sham operated rats treated with saline), model group (MCAO rats treated with saline) and TMP group (MCAO rats treated with 20 mg/kg/d TMP). The neurological function test of animals was evaluated using the modified neurological severity score (mNSS) at 3 d, 7 d, and 14 d after MCAO. Animals were euthanized for immunohistochemical labeling to measure MAP-2 levels in the peri-infarct area. Golgi-Cox staining was performed to test effect of TMP on dendritic plasticity at 14 d after MCAO. TMP significantly improved neurological function at 7 d and 14 d after ischemia, increased MAP-2 level at 14 d after ischemia, and enhanced spine density of basilar dendrites. TMP failed to affect the spine density of apical dendrites and the total dendritic length. Data analyses indicate that there was significant negative correlation between mNSS and plasticity measured at 14 d after MCAO. Thus, enhanced dendritic plasticity contributes to TMP-elicited functional recovery after ischemic stroke. PMID- 26379745 TI - The Mechanism Research of Qishen Yiqi Formula by Module-Network Analysis. AB - Qishen Yiqi formula (QSYQ) has the effect of tonifying Qi and promoting blood circulation, which is widely used to treat the cardiovascular diseases with Qi deficiency and blood stasis syndrome. However, the mechanism of QSYQ to tonify Qi and promote blood circulation is rarely reported at molecular or systems level. This study aimed to elucidate the mechanism of QSYQ based on the protein interaction network (PIN) analysis. The targets' information of the active components was obtained from ChEMBL and STITCH databases and was further used to search against protein-protein interactions by String database. Next, the PINs of QSYQ were constructed by Cytoscape and were analyzed by gene ontology enrichment analysis based on Markov Cluster algorithm. Finally, based on the topological parameters, the properties of scale-free, small world, and modularity of the QSYQ's PINs were analyzed. And based on function modules, the mechanism of QSYQ was elucidated. The results indicated that Qi-tonifying efficacy of QSYQ may be partly attributed to the regulation of amino acid metabolism, carbohydrate metabolism, lipid metabolism, and cAMP metabolism, while QSYQ improves the blood stasis through the regulation of blood coagulation and cardiac muscle contraction. Meanwhile, the "synergy" of formula compatibility was also illuminated. PMID- 26379746 TI - Biothermodynamic Assay of Coptis-Evodia Herb Couples. AB - Objective. To illustrate the difference in cold/hot natural properties and therapeutic effect of coptis-evodia herb couples by using cold/hot plate differentiating technology and microcalorimetry combined with material basis analysis in vivo and in vitro. It showed that animal retention ratio in hot pad significantly decreased along with the decrease in coptis proportion in coptis evodia herb couples. In addition, Zuojin wan markedly reduced the retention ratio of gastritis mice in the hot pad, while Fanzuojin wan displayed an opposite result. Further, Mg(2+)-ATPase, Ca(2+)-ATPase, and T-AOC activity significantly weakened in coptis-treated group in the livers of the mice. In the gastric cells from the gastritis mice, Fanzuojin wan remarkably increased calorific value for growth and metabolism, while Zuojin wan significantly reduced the calorigenic effect. It suggested that the changes in the major chemical compositions (especially alkaloids) were the material base-induced transformation between "cold" and "hot" syndromes. The material basis which affected the transformation between "cold" and "hot" syndromes might be X2, X3, X4, X8, epiberberine hydrochloride, jatrorrhizine hydrochloride, coptisine sulphate, palmatine hydrochloride, and berberine hydrochloride. The CHPD combined with microcalorimetry technology is a good method to determine the differences in the "cold" and "hot" natural properties of coptis-evodia herb couples. PMID- 26379747 TI - Hinokitiol Negatively Regulates Immune Responses through Cell Cycle Arrest in Concanavalin A-Activated Lymphocytes. AB - Autoimmune diseases are a group of chronic inflammatory diseases that arise from inappropriate inflammatory responses. Hinokitiol, isolated from the wood of Chamaecyparis taiwanensis, engages in multiple biological activities. Although hinokitiol has been reported to inhibit inflammation, its immunological regulation in lymphocytes remains incomplete. Thus, we determined the effects of hinokitiol on concanavalin A- (ConA-) stimulated T lymphocytes from the spleens of mice. In the present study, the MTT assay revealed that hinokitiol (1-5 MUM) alone did not affect cell viability of lymphocytes, but at the concentration of 5 MUM it could reduce ConA-stimulated T lymphocyte proliferation. Moreover, propidium iodide (PI) staining revealed that hinokitiol arrested cell cycle of T lymphocytes at the G0/G1 phase. Hinokitiol also reduced interferon gamma (IFN gamma) secretion from ConA-activated T lymphocytes, as detected by an ELISA assay. In addition, hinokitiol also downregulated cyclin D3, E2F1, and Cdk4 expression and upregulated p21 expression. These results revealed that hinokitiol may regulate immune responses. In conclusion, we for the first time demonstrated that hinokitiol upregulates p21 expression and attenuates IFN-gamma secretion in ConA-stimulated T lymphocytes, thereby arresting cell cycle at the G0/G1 phase. In addition, our findings also indicated that hinokitiol may provide benefits to treating patients with autoimmune diseases. PMID- 26379748 TI - Methyl Protodioscin from the Roots of Asparagus cochinchinensis Attenuates Airway Inflammation by Inhibiting Cytokine Production. AB - The present study was designed to find pharmacologically active compound against airway inflammation from the roots of Asparagus cochinchinensis. The 70% ethanol extract of the roots of A. cochinchinensis (ACE) was found to inhibit IL-6 production from IL-1beta-treated lung epithelial cells (A549) and the major constituent, methyl protodioscin (MP), also strongly inhibited the production of IL-6, IL-8, and tumor necrosis factor- (TNF-) alpha from A549 cells at 10-100 MUM. This downregulating effect of proinflammatory cytokine production was found to be mediated, at least in part, via inhibition of c-Jun N-terminal kinase (JNK) and c-Jun activation pathway. When examined on an in vivo model of airway inflammation in mice, lipopolysaccharide- (LPS-) induced acute lung injury, ACE, and MP significantly inhibited cell infiltration in the bronchoalveolar lavage fluid by the oral treatment at doses of 100-400 mg/kg and 30-60 mg/kg, respectively. MP also inhibited the production of proinflammatory cytokines such as IL-6, TNF-alpha, and IL-1beta in lung tissue. All of these findings provide scientific evidence supporting the role of A. cochinchinensis as a herbal remedy in treating airway inflammation and also suggest a therapeutic value of MP on airway inflammatory disorders. PMID- 26379749 TI - Comparison of Alcian Blue, Trypan Blue, and Toluidine Blue for Visualization of the Primo Vascular System Floating in Lymph Ducts. AB - The primo vascular system (PVS), floating in lymph ducts, was too transparent to be observed by using a stereomicroscope. It was only detectable with the aid of staining dyes, for instance, Alcian blue, which was injected into the lymph nodes. Some dyes were absorbed preferentially by the PVS than the lymph wall. It remains a standing problem to know what dyes are absorbed better by the PVS than the lymph walls. Such information would be useful to unravel the biochemical properties of the PVS that are badly in need for obtaining large amount of PVS specimens. In the current work we tried two other familiar dyes which were used in PVS research before. We found that Trypan blue and toluidine blue did not visualize the PVS. Trypan blue was cleared by the natural washing. Toluidine blue did not stain the PVS, but it did leave stained spots in the lymph wall and its surrounding tissues, and it leaked out of the lymph wall to stain surrounding connective tissues. These completely different behaviors of the three dyes were found for the first time in the current work and provide valuable information to elucidate the mechanism through which some special dyes stained the PVS preferentially compared to the lymphatic wall. PMID- 26379750 TI - Cardioprotective Potential of Polyphenolic Rich Green Combination in Catecholamine Induced Myocardial Necrosis in Rabbits. AB - The present study was designed to develop safer, effective, and viable cardioprotective herbal combination to control oxidative stress related cardiac ailments as new alternatives to synthetic drugs. The synergetic cardioprotective potential of herbal combination of four plants T. arjuna (T.A.), P. nigrum (P.N), C. grandiflorus (C), and C. oxyacantha (Cr) was assessed through curative and preventive mode of treatment. In preventive mode of treatment, the cardiac injury was induced with synthetic catecholamine (salbutamol) to pretreated rabbits with the proposed herbal combination for three weeks. In curative mode of treatment, cardiotoxicity/oxidative stress was induced in rabbits with salbutamol prior to treating them with plant mixture. Cardiac marker enzymes, lipids profile, and antioxidant enzymes as biomarker of cardiotoxicity were determined in experimental animals. Rabbits administrated with mere salbutamol showed a significant increase in cardiac marker enzymes and lipid profile and decrease in antioxidant enzymes as compared to normal control indicating cardiotoxicity and myocardial cell necrosis. However, pre- and postadministration of plant mixture appreciably restored the levels of all biomarkers. Histopathological examination confirmed that the said combination was safer cardioprotective product. PMID- 26379751 TI - Identification of Primo-Vascular System in Abdominal Subcutaneous Tissue Layer of Rats. AB - The primo-vascular system (PVS) is a novel network identified in various animal tissues. However, the PVS in subcutaneous tissue has not been well identified. Here, we examined the putative PVS on the surface of abdominal subcutaneous tissue in rats. Hemacolor staining revealed dark blue threadlike structures consisting of nodes and vessels, which were frequently observed bundled with blood vessels. The structure was filled with various immune cells including mast cells and WBCs. In the structure, there were inner spaces (20-60 um) with low cellularity. Electron microscopy revealed a bundle structure and typical cytology common with the well-established organ surface PVS, which were different from those of the lymphatic vessel. Among several subcutaneous (sc) PVS tissues identified on the rat abdominal space, the most outstanding was the scPVS aligned along the ventral midline. The distribution pattern of nodes and vessels in the scPVS closely resembled that of the conception vessel meridian and its acupoints. In conclusion, our results newly revealed that the PVS is present in the abdominal subcutaneous tissue layer and indicate that the scPVS tissues are closely correlated with acupuncture meridians. Our findings will help to characterize the PVS in the other superficial tissues and its physiological roles. PMID- 26379752 TI - Primo Vascular System: An Endothelial-to-Mesenchymal Potential Transitional Tissue Involved in Gastric Cancer Metastasis. AB - Gastric cancer is the fourth commonest cancer in the world and the second leading cause of cancer-related death. Investigation of gastric cancer metastasis is one of the hottest and major focuses in cancer research. Growing evidence manifested that primo vascular system (PVS) is a new kind of circulatory system beyond vascular and lymphatic system. Previous researches revealed that PVS is a specific tissue between endothelium and mesenchyme and is involved in cancer, especially in tumor metastasis and regeneration. In current study, we investigated the role of primo vessels in gastric cancer metastasis and its possible relationship to vascular vessels formation. Our results indicated that primo vessels were involved in gastric cancer metastasis. We observed blood vessel-mediated metastasis, primo vessel-mediated metastasis, and an intermediate state between them. We deduced that primo vessels may be precursors of blood vessels. These results possibly provided a thoroughly new theoretic development in cancer metastasis. PMID- 26379753 TI - Systemic Review and Meta-Analysis of the Clinical Efficacy and Adverse Effects of Zhengqing Fengtongning Combined with Methotrexate in Rheumatoid Arthritis. AB - Chinese medicines are gaining wider acceptance. They have been used for treating rheumatoid arthritis (RA) for thousands of years, and the need to investigate the interaction between Chinese medicines and western medicines is widely recognized. In this study, a large number of RCTs and CCTs were analyzed to systematically assess the effects and adverse events of Zhengqing Fengtongning (ZQFTN) for RA. Eleven studies that contained 956 participants (508 in the treatment group; 448 in the control group) were included. The results showed that although ZQFTN combined with methotrexate MTX could not decrease the swollen joint count and tender joint count of RA patients better than MTX alone, the combination therapy might relieve the duration of morning stiffness (SMD: -16.06; 95% CI: -28.77 to 3.34), reduce laboratory indexes (RF: SMD: -10.84; 95% CI: -19.39 to -2.29; ESR: SMD: -7.26; 95% CI: -11.54 to -2.99; CRP: SMD: -3.66; 95% CI: -5.94 to -1.38), and improve the overall effect (RR: 1.08; CI: 1.01 to 1.16) better than monotherapy. The combination therapy was significantly better in controlling adverse drug reactions (RR: 0.60; 95% CI: 0.46 to 0.79). Through this systematic review, we found that ZQFTN combined with MTX for the treatment of RA might have better clinical efficacy than MTX only and might be superior in terms of controlling adverse drug reactions. PMID- 26379754 TI - Intervention Effect of Electroacupuncture Combined with EPCs Transplantation on the Mice in Aging Model. AB - The results of this experiment suggested that electroacupuncture promotes the endothelialization of liver endothelial progenitor cells (EPCs) for mice in D-gal model and improves the repair of vascular endothelial function, as well as increasing the vascular endothelial growth factor (VEGF) expression in liver tissue fluorescence and KL protein levels. Also, it reduces the malondialdehyde (MDA) activity and delays vascular aging and even overall aging. Results showed that the in vivo fluorescence intensity for D-gal EA group was significantly lower than that of D-gal group, P < 0.05; VEGF fluorescence expression in liver tissue for D-gal EA group was significantly higher than that for D-gal group, P < 0.05; KL protein content in liver tissue for D-gal EA group was significantly higher than that for D-gal group, P < 0.05; MDA activity for D-gal EA group was significantly lower than that for D-gal group, P < 0.05. PMID- 26379755 TI - Visualizing sound: counting wolves by using a spectral view of the chorus howling. AB - INTRODUCTION: Monitoring large carnivores is a central issue in conservation biology. The wolf (Canis lupus) is the most studied large carnivore in the world. After a massive decline and several local extinctions, mostly due to direct persecutions, wolves are now recolonizing many areas of their historical natural range. One of the main monitoring techniques is the howling survey, which is based on the wolves' tendency to use vocalisations to mark territory ownership in response to howls of unknown individuals. In most cases wolf howling sessions are useful for the localisation of the pack, but they provide only an aural estimation of the chorus size. We tested and present a new bioacoustic approach to estimate chorus size by recording wolves' replies and visualising choruses through spectrograms and spectral envelopes. To test the methodology, we compared: a) the values detected by visual inspections with the true chorus size to test for accuracy; b) the bioacoustic estimations of a sample of free-ranging wolves' replies developed by different operators to test for precision of the method; c) the aural field estimation of chorus size of a sample of free-ranging wolves' replies with the sonogram analysis of the same recordings to test for difference between methods. RESULTS: Visual inspection of the chorus by spectrogram and spectrum proved to be useful in determining the number of concurrent voices in a wolf chorus. Estimations of chorus size were highly correlated with the number of wolves counted in a pack, and 92 % of 29 known chorus sizes were recognized by means of bioacoustic analysis. On the basis of spectrographic evidence, it was also possible to identify up to seven concurrent vocalisations in a chorus of nine wolves. Spectral analysis of 37 free ranging wolves' replies showed a high correlation between the chorus size estimations of the different operators (92.8 %), but a low correlation with the aural estimation (59.2 %). CONCLUSIONS: Wolf howling monitoring technique could be improved by recording wolves' replies and by using bioacoustic tools such as spectrograms and spectral envelopes to determine the size of the wolf chorus. Compared with other monitoring techniques (i.e., genetic analysis), bioacoustic analysis requires widely available informatic tools (i.e., sound recording set of devices and sound analysis software) and a low budget. Information obtained by means of chorus analysis can also be combined with that provided by other techniques. Moreover, howls can be recorded and stored in audio file format with a good resolution (i.e. in "Wave" format), thus representing a useful tool for future listening and investigations, which can be countlessly employed without risks of time deterioration. PMID- 26379756 TI - The phantoms of a high-seven - or - why do our thumbs stick out? AB - The earliest tetrapods had hands and feet with up to eight digits but this number was subsequently reduced during evolution. It was assumed that lineages with more than five digits no longer exist but investigations of clawed-frogs now indicate that they posses a rudimentary or atavistic sixth digit in their hindlimb. A recent reevaluation of the stem tetrapod Ichthyostega predicts that its seven digits evolved from two different types of ancestral fin radials, pre-axial and post-axial. In this context we now ask the question, should we consider a pre axial origin of the thumb as reason for its unique genetic signature? PMID- 26379757 TI - Dietary restriction in obese children and its relation with eating behavior, fibroblast growth factor 21 and leptin: a prospective clinical intervention study. AB - BACKGROUND: Obesity is significant problem involving eating behavior and peripheral metabolic conditions. The effect of carbohydrate and fat restriction on appetite regulation, fibroblast growth factor 21 (FGF21) and leptin in children has not been defined. Our objective was to compare the effect of both diets. METHODS: One hundred and twenty children with body mass index (BMI) higher than the equivalent of 30 kg/m(2) for an adult, as corrected for gender and age were randomly assigned to (n = 60) a low-carbohydrate (L-CHO) diet or (n = 60) a low-fat (L-F) diet for 2 months. Fifty-three (88.3 %) subjects on the low carbohydrate-diet and 45 (75 %) on the low-fat diet completed the study. Anthropometric measures, leptin and FGF21 levels were measured before and after the intervention. Comparison of the data for both of the diet groups was carried out using the t-test for independent variables. Intragroup comparisons before and after of each of the dietary treatments were performed using ANOVA for repeated measures. Factors associated with FGF21, leptin levels and satiety, were analyzed by multiple regression. RESULTS: After both of the diets, weight, leptin, food responsiveness, and enjoyment of food significantly decreased and high density lipoprotein cholesterol (HDL) increased, but FGF21 decreased. Before and after both of the interventions FGF21 was associated with triglycerides. Before the diet, satiety was associated with lower screen time (p < 0.04) and insulin levels (p < 0.05). CONCLUSIONS: Both dietary restrictions improved the metabolic and hormonal parameters of obese children. FGF21 is an indicator of a beneficial metabolic response in younger children. After 2 months an adaptation of the eating behavior to food restriction was observed. PMID- 26379758 TI - A systematic appraisal of allegiance effect in randomized controlled trials of psychotherapy. AB - BACKGROUND: Experimenter's allegiance (EA) refers to a personal confidence of the superiority of a specific psychotherapy treatment. This factor has been linked with larger treatment effects in favor of the preferred treatment. However, various studies have displayed contradictory results between EA and the pattern of treatment effects. AIMS: Using a systematic approach followed by meta analysis, we aimed to evaluate the impact of an allegiance effect on the results of psychotherapeutic studies. METHOD: We considered the meta-analyses of randomized controlled trials (RCTs) of different types of psychotherapies in the Cochrane Database of Systematic Reviews. Eligible articles included meta-analyses of RCTs with at least one study showing evidence of EA (i.e., allegiant study). Effect sizes in allegiant RCTs were compared with non-allegiant using random and fixed models and a summary relative odds ratio (ROR) were calculated. Heterogeneity was quantified with the I (2) metric. RESULTS: A total of 30 meta analyses including 240 RCTs were analyzed. The summary ROR was 1.31 [(95 % confidence interval (CI: 1.03-1.66) P = 0.30, I (2) = 53 %] indicating larger effects when allegiance exists. The impact of allegiance did not differ significantly (P > 0.05) when we compared psychiatric versus medical outcomes. Allegiance effect was significant for all forms of psychotherapy except for cognitive behavioral therapy. Moreover, the impact of allegiance was significant only when the treatment integrity of delivered psychotherapy was not assessed. Allegiance effect was even stronger where the experimenter was also both the developer of the preferred treatment and supervised or trained the therapists. No significant differences were found between allegiant and non-allegiant studies in terms of overall quality of studies. CONCLUSIONS: Experimenter's allegiance influences the effect sizes of psychotherapy RCTs and can be considered non financial conflict of interest introducing a form of optimism bias, especially since blinding is problematic in this kind of research. A clear reporting of EA in every single study should be given an opportunity to investigators of minimizing its overestimation effects. PMID- 26379759 TI - A controlled trial of quetiapine XR coadministration treatment of SSRI-resistant panic disorder. AB - BACKGROUND: Open-label quetiapine coadministration with SSRI therapy, in a diagnostically mixed sample of comorbid anxiety patients, offered additional anxiolytic benefit. Therefore, we designed the following controlled trial to confirm these findings in a comorbid, SSRI-resistant, panic disorder (PD) patient sample. METHODS: This was a single-site, double-blind, placebo-controlled (PLAC), randomized, parallel group (2 groups), 8-week, quetiapine extended release (XR) coadministration trial. SSRI resistance was determined either historically or prospectively. Patients were randomized if they remained moderately ill (CGI-S score >= 4). Change in the PDSS scale total score was the primary efficacy outcome measure. Responders were identified as those with a >=50 % decrease from their baseline PDSS score. In the early weeks of therapy, XR was flexibly and gradually titrated from 50 to 400 mg/day. RESULTS: 43 patients were screened in total, and 26 of these were randomized and evaluable. 21 patients (78 % of the randomized group) completed the trial (10 XR; 11 PLAC). The endpoint quetiapine XR mean daily dose +/- SD was 150 +/- 106 mg. While, in the sample as a whole, there was improvement in PDSS scores across the 8-week trial (ANOVA main effect of time, F = 10.9, df 8,192, p < 0.0001), the treatment * time interaction effect was not statistically significant (F = 0.8, df 8,192, p = 0.61). There was no between-group difference in responder frequency at endpoint. CONCLUSIONS: This proof-of-concept RCT did not support the efficacy of this treatment strategy for SSRI-resistant PD. Quetiapine XR was generally well-tolerated. Important limitations were the small sample size, and the relatively low average dose of quetiapine XR used. ClinicalTrials.gov ID#: NCT00619892. PMID- 26379760 TI - Therapeutic intervention in Crimean-Congo hemorrhagic fever: where are we now? PMID- 26379761 TI - Risk Prediction of One-Year Mortality in Patients with Cardiac Arrhythmias Using Random Survival Forest. AB - Existing models for predicting mortality based on traditional Cox proportional hazard approach (CPH) often have low prediction accuracy. This paper aims to develop a clinical risk model with good accuracy for predicting 1-year mortality in cardiac arrhythmias patients using random survival forest (RSF), a robust approach for survival analysis. 10,488 cardiac arrhythmias patients available in the public MIMIC II clinical database were investigated, with 3,452 deaths occurring within 1-year followups. Forty risk factors including demographics and clinical and laboratory information and antiarrhythmic agents were analyzed as potential predictors of all-cause mortality. RSF was adopted to build a comprehensive survival model and a simplified risk model composed of 14 top risk factors. The built comprehensive model achieved a prediction accuracy of 0.81 measured by c-statistic with 10-fold cross validation. The simplified risk model also achieved a good accuracy of 0.799. Both results outperformed traditional CPH (which achieved a c-statistic of 0.733 for the comprehensive model and 0.718 for the simplified model). Moreover, various factors are observed to have nonlinear impact on cardiac arrhythmias prognosis. As a result, RSF based model which took nonlinearity into account significantly outperformed traditional Cox proportional hazard model and has great potential to be a more effective approach for survival analysis. PMID- 26379762 TI - Dependence of Shape-Based Descriptors and Mass Segmentation Areas on Initial Contour Placement Using the Chan-Vese Method on Digital Mammograms. AB - Variation in signal intensity within mass lesions and missing boundary information are intensity inhomogeneities inherent in digital mammograms. These inhomogeneities render the performance of a deformable contour susceptible to the location of its initial position and may lead to poor segmentation results for these images. We investigate the dependence of shape-based descriptors and mass segmentation areas on initial contour placement with the Chan-Vese segmentation method and compare these results to the active contours with selective local or global segmentation model. For each mass lesion, final contours were obtained by propagation of a proposed initial level set contour and by propagation of a manually drawn contour enclosing the region of interest. Differences in shape based descriptors were quantified using absolute percentage differences, Euclidean distances, and Bland-Altman analysis. Segmented areas were evaluated with the area overlap measure. Differences were dependent upon the characteristics of the mass margins. Boundary moments presented large percentage differences. Pearson correlation analysis showed statistically significant correlations between shape-based descriptors from both initial locations. In conclusion, boundary moments of digital mass lesions are sensitive to the placement of initial level set contours while shape-based descriptors such as Fourier descriptors, shape convexity, and shape rectangularity exhibit a certain degree of robustness to changes in the location of the initial level set contours for both segmentation algorithms. PMID- 26379763 TI - Elevated white blood cell count, decreased hematocrit and presence of macrohematuria correlate with abdominal organ injury in pediatric blunt trauma patients: a retrospective study. AB - INTRODUCTION: Computerized tomography (CT) has become an important diagnostic modality in trauma patients. Pediatric patients are particularly susceptible to ionized radiation making liberal CT use in this age group unacceptable. We aimed to identify parameters that might predict abnormal findings on abdominal CT leading to patient management changes. METHODS: Data on blunt trauma patients up to 15 years of age admitted to Assaf Harofeh Medical Center from January 2007 to October 2014 was retrospectively collected. All patients with abdominal CT scan as part of initial assessment were included. Medical and surgical data were extracted from the medial charts. Patients were divided into two groups. Group I: patients whose management was changed solely based on abdominal CT findings and Group II: patients with normal abdominal CT. The groups were compared by all the data parameters. RESULTS: Overall, 182 patients were included in the study. The groups were comparable by age and mechanism of injury. Management changes based on CT findings were found in 68 (37.4 %) patients. White blood cell count >14000, abnormally low hematocrit level and macrohematuria were associated with a diagnosis of intra-abdominal injury requiring patient management changes (p < 0.05). Group I patients had longer LOS. Fifteen patients (22 %) required active intervention based solely on CT findings. Physical examination, arterial blood gases and initial radiology examinations results did not correlate with abdominal CT findings. CONCLUSIONS: Elevated WBC, decreased hematocrit and presence of macrohematuria strongly correlate with abdominal CT findings and lead to changes in patient management. PMID- 26379764 TI - The significance of Bartonella henselae bacterias for oncological diagnosis in children. AB - BACKGROUND: Cat-scratch disease (CSD) is a common infection in children; however, the wide spectrum of its clinical picture may lead to delayed diagnosis. An unusual presentation of CSD includes in the differential diagnosis malignant diseases, Epstein-Barr and cytomegalovirus infections, tuberculosis, and mycobacterioses. The diagnostic procedure is difficult, and it is important to consider CSD as the etiology of untypical lesion. PATIENTS AND METHOD: We present the analysis of 22 immunocompetent children treated with the clinical diagnosis of CSD in our hospital. Their ages were 2 to 16 years (mean 9.15 +/- 2.2 years). Four of them presented classical papulas at admission time. Asymmetric, local lymphadenopathy was present in 16 patients. Five children, who presented an untypical course of CSD mimicking the oncological process, were analysed carefully. There were 3 patients with skull osteomyelitis, 1 with inflammation of the parotid gland, and 1 with an extra peripharyngeal mass. The diagnosis in these children was based on epidemiological, radiological, serological, and histological factors. RESULTS: About 25 % of children with bartonellosis present an untypical spectrum of symptoms, including the lack of documented cat contact, primary lesions, or peripheral lymphadenopathy. Radiological methods like USG, CT, MRI present the unspecific masses, but they are not enough to distinguish the Bartonella inflammatory and oncological process. The final diagnosis was based on a histological method with additional polymerase chain reaction test. CONCLUSION: CSD should be considered in differential diagnosis of any patient with untypical lesions located on the head, neck, and upper extremities. PMID- 26379765 TI - A Pilot Study Examining the Use of the Autism Diagnostic Observation Schedule in Community-Based Mental Health Clinics. AB - Community-based mental health (CMH) services play an important, but relatively understudied role in the identification and treatment of youth with autism spectrum disorder (ASD) who may be receiving care for other psychiatric conditions. Little is known about the role of standardized ASD assessment measures administered by providers working in generalist community-based mental health (CMH) settings. This pilot study extracted data from three CMH clinics to examine the use of the Autism Diagnostic Observation Schedule (ADOS) by 17 CMH providers who received ASD assessment training with 62 youth (Mean = 10.69 years) referred for an ASD diagnostic evaluation. Results indicated that 57% of youths assessed ultimately received an ASD diagnosis. All cases given a final ASD diagnosis were classified as "Autism" or "ASD" on the ADOS. Seventy percent of youth who did not receive a final ASD diagnosis were classified as "Non-Spectrum" on the ADOS. In these false positive cases, report narratives indicated that social communication difficulties identified on the ADOS were explained by symptoms of other mental health conditions (e.g., ADHD, anxiety). Future research is needed to examine the utility of the ADOS when used by CMH providers to facilitate CMH capacity to identify ASD. PMID- 26379766 TI - Pathways Between Concealable Stigmatized Identities and Substance Misuse. AB - Individuals with concealable stigmatized identities often possess no obviously devalued attributes, yet are at greater risk for problematic substance use compared to their privileged counterparts. We present a conceptual model, which proposes that identity-relevant content and characteristics have important implications for cognitive, affective, and behavioral consequences of stigma related stress. In doing so, we synthesize stigma-related models from the extant literature and attempt to integrate these concepts with previous work detailing potential contributors to substance use behaviors specifically. Finally, we ask readers to consider the various ways in which the content and characteristics of an individual's stigmatized identity might combine with situational and additional individual difference factors to influence the likelihood of substance misuse. PMID- 26379767 TI - Conflict, displacement and sexual and reproductive health services in Mali: analysis of 2013 health resources availability mapping system (HeRAMS) survey. AB - OBJECTIVE: Little is known specifically about the effects of conflict and displacement on provision of sexual and reproductive health (SRH) services. We aimed to understand the association between levels of conflict and displacement and the availability of SRH services in post-conflict Mali. METHODS: A national assessment was conducted between April and May 2013 employing Health Systems Availability Mapping System (HeRAMS). Data from 1581 primary care facilities were analysed, focusing on SRH services. Descriptive analyses and multivariable logistic regression models were used to examine the availability of SRH services by different levels of conflict and displacement. FINDINGS: Of 1581 facilities, 1551 had data available to identify the details of service provision. The majority of the facilities were part of the public sector (79.1 %), identified as basic community primary care facilities (71.9 %). Overall 15.7 % of the facilities were in the zones under occupation, 40.3 % in the areas with high concentration of displaced population and 44 % in areas with low concentration of displaced populations. Between zones of low concentration of displaced populations and under occupation the likelihood of service availability varied between OR: 2.9 (95 % CI 2.0-4.4) for basic emergency obstetric care and OR: 41.7 (95 % CI 20.4-85.3) for family planning. All of the services within the three domains of SRH were more likely to be available in the low and high concentration displaced population areas compared to the facilities in the under occupation zones, after adjusting for other facility-related variables. CONCLUSION: Areas with high concentration of displaced population had less service availability, and areas formerly under occupation had the least service availability. This suggests that those living in conflict areas, and many of those who are internally displaced, have poor access to essential SRH interventions. The systematic measurement of the availability of health services, including SRH, is feasible and can contribute to recovery planning in post-conflict and humanitarian settings. PMID- 26379768 TI - Sandal reactive dyes decolorization and cytotoxicity reduction using manganese peroxidase immobilized onto polyvinyl alcohol-alginate beads. AB - BACKGROUND: Fungal manganese peroxidases (MnPs) have great potential as bio remediating agents and can be used continuously in the immobilized form like many other enzymes. RESULTS: In the present study, purified manganese peroxidase (MnP) enzyme isolated from Ganoderma lucidum IBL-05 was immobilized onto polyvinyl alcohol-alginate beads and investigated its potential for the decolorization and detoxification of new class of reactive dyes and textile wastewater. The optimal conditions for MnP immobilization were 10 % (w/v) PVA, 1.5 % sodium alginate, 3 % boric acid and 2 % CaCl2 solution. The optimum pH, temperature and kinetic parameters (K m and V max ) for free and immobilized MnP were found to be significantly altered after immobilization. The immobilized MnP showed high decolorization efficiency for Sandal reactive dyes (78.14-92.29 %) and textile wastewater (61-80 %). Reusability studies showed that after six consecutive dye decolorization cycles, the PVA coupled MnP retained more than 60 % of its initial activity (64.9 % after 6th cycle form 92.29 % in 1st cycle) for Sandal-fix Foron Blue E2BLN dye. The water quality assurance parameters (BOD, COD and TOC) and cytotoxicity (haemolytic and brine shrimp lethality tests) studies before and after treatment were employed and results revealed that both the dyes aqueous solution and textile wastewater were cytotoxic that reduced significantly after treatment. CONCLUSIONS: The decolorization and cytotoxicity outcomes indicated that immobilized MnP in PVA-alginate beads can be efficiently exploited for industrial and environmental applications, especially for remediation of textile dyes containing wastewater effluents. Graphical abstractDye decolorizing potential of immobilized MnP. PMID- 26379769 TI - A bioenergetic assessment of photosynthetic growth of Synechocystis sp. PCC 6803 in continuous cultures. AB - BACKGROUND: Synechocystis sp. PCC 6803, a model organism used for bioenergy and bioplastic production, was grown in continuous culture to assess its most important bioenergetic parameters. RESULTS: Biomass yield on light energy of 1.237 g mol photons(-1) and maintenance energy requirement of 0.00312 mol photons g(-1) h(-1) were calculated. This corresponded to a light conversion efficiency of 12.5 %, based on the model of Pirt which was about 35 % lower than the theoretical one based on the stoichiometric equation for the formation of biomass on carbon dioxide, water, and nitrate. The maximum F v/F m ratio recorded in the Synechocystis cultures was 0.57; it progressively declined to 0.45 as the dilution rate increased. An over-reduction of reaction centers at a high dilution rate was also recorded, together with an increased VJ phase for the chlorophyll fluorescence transient. In contrast, the chlorophyll optical cross section increased by about 40 % at the fastest dilution rate, and compensated for the decline in F v/F m, thus resulting in a constant total photosynthesis rate (photosynthesis plus respiration). Chlorophyll content was maximum at the lowest dilution rate and was 48 % lower at the highest one, while phycocyanin, and total carotenoids decreased by about 42 % and 37 %, respectively. Carotenoid analysis revealed increased echinenone, zeaxanthin, and myxoxanthophyll contents as the dilution rate increased (40.6, 63.8 and 35.5 %, respectively, at the fastest dilution rate). A biochemical analysis of the biomass harvested at each different dilution rates showed no changes in the lipid content (averaging 11.2 +/- 0.6 % of the dry weight), while the protein content decreased as the dilution rate increased, ranging between 60.7 +/- 1.1 and 72.6 +/- 0.6 %. Amino acids pattern did not vary with the dilution rate. Carbohydrate content ranged from 9.4 to 16.2 % with a mean value of 11.2 +/- 1.4 %. CONCLUSIONS: The present work provides useful information on the threshold of light conversion efficiency in Synechocystis, as well as basic bioenergetic parameters that will be helpful for future studies related to its genetic transformation and metabolic network reconstruction. PMID- 26379770 TI - Physiological roles of pyruvate ferredoxin oxidoreductase and pyruvate formate lyase in Thermoanaerobacterium saccharolyticum JW/SL-YS485. AB - BACKGROUND: Thermoanaerobacter saccharolyticum is a thermophilic microorganism that has been engineered to produce ethanol at high titer (30-70 g/L) and greater than 90 % theoretical yield. However, few genes involved in pyruvate to ethanol production pathway have been unambiguously identified. In T. saccharolyticum, the products of six putative pfor gene clusters and one pfl gene may be responsible for the conversion of pyruvate to acetyl-CoA. To gain insights into the physiological roles of PFOR and PFL, we studied the effect of deletions of several genes thought to encode these activities. RESULTS: It was found that pyruvate ferredoxin oxidoreductase enzyme (PFOR) is encoded by the pforA gene and plays a key role in pyruvate dissimilation. We further demonstrated that pyruvate formate-lyase activity (PFL) is encoded by the pfl gene. Although the pfl gene is normally expressed at low levels, it is crucial for biosynthesis in T. saccharolyticum. In pforA deletion strains, pfl expression increased and was able to partially compensate for the loss of PFOR activity. Deletion of both pforA and pfl resulted in a strain that required acetate and formate for growth and produced lactate as the primary fermentation product, achieving 88 % theoretical lactate yield. CONCLUSION: PFOR encoded by Tsac_0046 and PFL encoded by Tsac_0628 are only two routes for converting pyruvate to acetyl-CoA in T. saccharolyticum. The physiological role of PFOR is pyruvate dissimilation, whereas that of PFL is supplying C1 units for biosynthesis. PMID- 26379771 TI - Gaseous ammonia pretreatment lowers the required energy input for fine milling enhanced enzymatic saccharification of switchgrass. AB - BACKGROUND: Fine milling of dry lignocellulosic biomass, without prior chemical pretreatment, can produce a high percent theoretical yield of sugars during subsequent enzymatic saccharification. However, the high sugar yields, necessary for a commercial biofuels process, are costly, with the milling energy input, necessary to achieve such yields even exceeding the energy content of the biomass. In this study, we show that low moisture gaseous ammonia pretreatment of switchgrass, in advance of the milling step, significantly reduces the milling energy required to give high sugar titers. RESULTS: We have found that the increase in monomeric sugar yields upon enzymatic saccharification of ball milled, but not chemically treated switchgrass, is more closely tied to the formation of crystallites of cellulose with a negative linear dependence on the coherent domain size than to a decrease in particle size or to an increase in surface area of the biomass. The milling energy required to reach ~80 % of theoretical yield of glucose under these conditions is intolerably high, however, approximating two times the energy content of the biomass. Two different low moisture content ammonia pretreatments, prior to milling, significantly reduce the required milling energy (four to eightfold, depending on the pretreatment). These involve either heating the biomass at 150-160 degrees C for 1 h at 10 wt% gaseous ammonia or incubating at room temperature for 9 days at 20 wt% gaseous ammonia, the latter mimicking potential treatment during biomass storage. We have tested this combination of pretreatment and milling on switchgrass using a variety of milling methods, but mostly using ball and attritor milling. In the case of the high-temperature gaseous ammonia treatment followed by attritor milling, the increase in the monomeric sugar yield upon saccharification shows a negative linear dependence on the second or third power of the cellulose crystalline coherent domain size, implying that the surfaces as well as the ends of the cellulose fibrils are accessible to cellulolytic enzymes. CONCLUSIONS: The combination of knife milling, low moisture gaseous ammonia pretreatment followed by attritor milling that costs only ~5 % of the energy content of the biomass for a total energy input of ~11 % of the biomass energy content, is capable of delivering high sugar titers upon enzymatic saccharification. These results show, therefore, how to better integrate a mechanochemical step into the pretreatment of switchgrass in a commercial biomass to biofuels conversion process. PMID- 26379772 TI - Ultrasonic intensification as a tool for enhanced microbial biofuel yields. AB - Ultrasonication has recently received attention as a novel bioprocessing tool for process intensification in many areas of downstream processing. Ultrasonic intensification (periodic ultrasonic treatment during the fermentation process) can result in a more effective homogenization of biomass and faster energy and mass transfer to biomass over short time periods which can result in enhanced microbial growth. Ultrasonic intensification can allow the rapid selective extraction of specific biomass components and can enhance product yields which can be of economic benefit. This review focuses on the role of ultrasonication in the extraction and yield enhancement of compounds from various microbial sources, specifically algal and cyanobacterial biomass with a focus on the production of biofuels. The operating principles associated with the process of ultrasonication and the influence of various operating conditions including ultrasonic frequency, power intensity, ultrasonic duration, reactor designs and kinetics applied for ultrasonic intensification are also described. PMID- 26379773 TI - Mechanism, kinetics and microbiology of inhibition caused by long-chain fatty acids in anaerobic digestion of algal biomass. AB - BACKGROUND: Oleaginous microalgae contain a high level of lipids, which can be extracted and converted to biofuel. The lipid-extracted residue can then be further utilized through anaerobic digestion to produce biogas. However, long chain fatty acids (LCFAs) have been identified as the main inhibitory factor on microbial activity of anaerobic consortium. In this study, the mechanism of LCFA inhibition on anaerobic digestion of whole and lipid-extracted algal biomass was investigated with a range of calcium concentrations against various inoculum to substrate ratios as a means to alleviate the LCFA inhibition. RESULTS: Whole algal biomass of Nannochloropsis salina represents high lipid content algal biomass while lipid-extracted residue represents its low lipid counterpart. The anaerobic digestion experiments were conducted in a series of serum bottles at 35 degrees C for 20 days. A kinetic model, considering LCFA inhibition on hydrolysis, acidogenesis as well as methanogenesis steps, was developed from the observed phenomenon of inhibition factors as a function of the LCFA concentration and specific biomass content or calcium concentration. The results showed that inoculum to substrate ratio had a stronger effect on biogas production than calcium, and calcium had no effect on biogas production when inoculum concentration was extremely low. The microbial community analysis by high throughput Illumina Miseq sequencing indicated that diversity of both bacterial and methanogenic communities decreased with elevation of lipid concentration. Hydrolytic bacteria and aceticlastic methanogens dominated bacterial and archaea communities, respectively, in both high and low LCFA concentration digesters. CONCLUSIONS: This study demonstrated that inoculum concentration has a more significant effect on alleviating LCFA inhibition than calcium concentration, while calcium only played a role when inoculum concentration met a threshold level. The model revealed that each functional microbial group was subject to different levels of LCFA inhibition. Although methanogens were the most susceptible microbes to LCFA inhibition, the inhibition factor for hydrolytic bacteria was more highly affected by inoculum concentration. The microbial community analysis indicated that the bacterial community was affected more than the methanogenic community by high LCFAs concentration. Syntrophic acetogens were sensitive to high LCFA concentrations and thus showed a decreased abundance in such an environment. Graphical abstractProposed mechanism of calcium mitigated LCFA inhibition. PMID- 26379774 TI - Increasing proline and myo-inositol improves tolerance of Saccharomyces cerevisiae to the mixture of multiple lignocellulose-derived inhibitors. AB - BACKGROUND: The development of robust microbes with tolerance to the combined lignocellulose-derived inhibitors is critical for the efficient cellulosic ethanol production. However, the lack of understanding on the inhibition mechanism limited the rational engineering of tolerant strain. Here, through the metabolomic analysis of an adaptation process of Saccharomyces cerevisiae to representative inhibitors, i.e., furfural, acetic acid and phenol (FAP), we figured out the new candidates for improving inhibitor tolerance. RESULTS: After metabolomic analysis, proline and myo-inositol were identified as the potential metabolites responsible for strain tolerance to inhibitors. The deletion of genes involved in proline or myo-inositol synthesis weakened strain tolerance against FAP stress. On the contrary, the addition of proline or myo-inositol in medium exerted a protective effect on cell growth under FAP stress. Furthermore, the enhancement of proline or myo-inositol synthesis by overexpressing key gene PRO1 or INO1 conferred yeast strain significantly increased FAP tolerance. All the recombinant strains finished the fermentation within 60 h under FAP stress, while the control strain was still in the lag phase. Meanwhile, it was found that the intracellular level of reactive oxygen species (ROS) under FAP condition was decreased with the increase of proline content, suggesting the function of proline as a ROS scavenger to protect strains from inhibitor damage. CONCLUSION: Increasing proline and myo-inositol were uncovered as the new determinants for improving strain tolerance to FAP under the guidance of metabolomics. Meanwhile, this study displayed the powerful application of metabolomics to develop rational strategies to increase stress tolerance and provided valuable insights into the design of recombinant microbes for the complex traits. PMID- 26379775 TI - Metabolic engineering of Escherichia coli for production of (2S,3S)-butane-2,3 diol from glucose. AB - BACKGROUND: Butane-2,3-diol (2,3-BD) is a fuel and platform biochemical with various industrial applications. 2,3-BD exists in three stereoisomeric forms: (2R,3R)-2,3-BD, meso-2,3-BD and (2S,3S)-2,3-BD. Microbial fermentative processes have been reported for (2R,3R)-2,3-BD and meso-2,3-BD production. RESULTS: The production of (2S,3S)-2,3-BD from glucose was acquired by whole cells of recombinant Escherichia coli coexpressing the alpha-acetolactate synthase and meso-butane-2,3-diol dehydrogenase of Enterobacter cloacae subsp. dissolvens strain SDM. An optimal biocatalyst for (2S,3S)-2,3-BD production, E. coli BL21 (pETDuet-PT7-budB-PT7-budC), was constructed and the bioconversion conditions were optimized. With the addition of 10 mM FeCl3 in the bioconversion system, (2S,3S)-2,3-BD at a concentration of 2.2 g/L was obtained with a stereoisomeric purity of 95.0 % using the metabolically engineered strain from glucose. CONCLUSIONS: The engineered E. coli strain is the first one that can be used in the direct production of (2S,3S)-2,3-BD from glucose. The results demonstrated that the method developed here would be a promising process for efficient (2S,3S) 2,3-BD production. PMID- 26379776 TI - A metabolomics-based strategy for identification of gene targets for phenotype improvement and its application to 1-butanol tolerance in Saccharomyces cerevisiae. AB - BACKGROUND: Traditional approaches to phenotype improvement include rational selection of genes for modification, and probability-driven processes such as laboratory evolution or random mutagenesis. A promising middle-ground approach is semi-rational engineering, where genetic modification targets are inferred from system-wide comparison of strains. Here, we have applied a metabolomics-based, semi-rational strategy of phenotype improvement to 1-butanol tolerance in Saccharomyces cerevisiae. RESULTS: Nineteen yeast single-deletion mutant strains with varying growth rates under 1-butanol stress were subjected to non-targeted metabolome analysis by GC/MS, and a regression model was constructed using metabolite peak intensities as predictors and stress growth rates as the response. From this model, metabolites positively and negatively correlated with growth rate were identified including threonine and citric acid. Based on the assumption that these metabolites were linked to 1-butanol tolerance, new deletion strains accumulating higher threonine or lower citric acid were selected and subjected to tolerance measurement and metabolome analysis. The new strains exhibiting the predicted changes in metabolite levels also displayed significantly higher growth rate under stress over the control strain, thus validating the link between these metabolites and 1-butanol tolerance. CONCLUSIONS: A strategy for semi-rational phenotype improvement using metabolomics was proposed and applied to the 1-butanol tolerance of S. cerevisiae. Metabolites correlated with growth rate under 1-butanol stress were identified, and new mutant strains showing higher growth rate under stress could be selected based on these metabolites. The results demonstrate the potential of metabolomics in semi-rational strain engineering. PMID- 26379777 TI - Lignin engineering through laccase modification: a promising field for energy plant improvement. AB - Laccase (p-diphenol:dioxygen oxidoreductase, EC 1.10.3.2) is a member of the multicopper oxidases and catalyzes the one-electron oxidation of a wide range of substrates, coupled with the reduction of oxygen to water. It is widely distributed in bacteria, fungi, plants and insects. Laccases are encoded by multigene family, and have been characterized mostly from fungi till now, with abundant industrial applications in pulp and paper, textile, food industries, organic synthesis, bioremediation and nanobiotechnology, while limited researches have been performed in plants, and no application has been reported. Plant laccases share the common molecular architecture and reaction mechanism with fungal ones, despite of difference in redox potential and pH optima. Plant laccases are implicated in lignin biosynthesis since genetic evidence was derived from the Arabidopsis LAC4 and LAC17. Manipulation of plant laccases has been considered as a promising and innovative strategy in plant biomass engineering for desirable lignin content and/or composition, since lignin is the major recalcitrant component to saccharification in biofuel production from lignocellulose, and therefore directly limits the fermentation yields. Moreover, plant laccases have been reported to be involved in wound healing, maintenance of cell wall structure and integrity, and plant responses to environmental stresses. Here, we summarize the properties and functions of plant laccase, and discuss the potential of biotechnological application, thus providing a new insight into plant laccase, an old enzyme with a promising beginning in lignocellulose biofuel production. PMID- 26379778 TI - High production of 2,3-butanediol from biodiesel-derived crude glycerol by metabolically engineered Klebsiella oxytoca M1. AB - BACKGROUND: 2,3-Butanediol (2,3-BDO) is a promising bio-based chemical because of its wide industrial applications. Previous studies on microbial production of 2,3 BDO has focused on sugar fermentation. Alternatively, biodiesel-derived crude glycerol can be used as a cheap resource for 2,3-BDO production; however, a considerable formation of 1,3-propanediol (1,3-PDO) and low concentration, productivity, and yield of 2,3-BDO from glycerol fermentation are limitations. RESULTS: Here, we report a high production of 2,3-BDO from crude glycerol using the engineered Klebsiella oxytoca M3 in which pduC (encoding glycerol dehydratase large subunit) and ldhA (encoding lactate dehydrogenase) were deleted to reduce the formation of 1,3-PDO and lactic acid. In fed-batch fermentation with the parent strain K. oxytoca M1, crude glycerol was more effective than pure glycerol as a carbon source in 2,3-BDO production (59.4 vs. 73.8 g/L) and by-product reduction (1,3-PDO, 8.9 vs. 3.7 g/L; lactic acid, 18.6 vs. 9.8 g/L). When the double mutant was used in fed-batch fermentation with pure glycerol, cell growth and glycerol consumption were significantly enhanced and 2,3-BDO production was 1.9-fold higher than that of the parent strain (59.4 vs. 115.0 g/L) with 6.9 g/L of 1,3-PDO and a small amount of lactic acid (0.7 g/L). Notably, when crude glycerol was supplied, the double mutant showed 1,3-PDO-free 2,3-BDO production with high concentration (131.5 g/L), productivity (0.84 g/L/h), and yield (0.44 g/g crude glycerol). This result is the highest 2,3-BDO production from glycerol fermentation to date. CONCLUSIONS: 2,3-BDO production from glycerol was dramatically enhanced by disruption of the pduC and ldhA genes in K. oxytoca M1 and 1,3-PDO-free 2,3-BDO production was achieved by using the double mutant and crude glycerol. 2,3-BDO production obtained in this study is comparable to 2,3 BDO production from sugar fermentation, demonstrating the feasibility of economic industrial 2,3-BDO production using crude glycerol. PMID- 26379779 TI - Engineering Yarrowia lipolytica to produce biodiesel from raw starch. AB - BACKGROUND: In the last year, the worldwide concern about the abuse of fossil fuels and the seeking for alternatives sources to produce energy have found microbial oils has potential candidates for diesel substitutes. Yarrowia lipolytica has emerged as a paradigm organism for the production of bio-lipids in white biotechnology. It accumulates high amounts of lipids from glucose as sole carbon sources. Nonetheless, to lower the cost of microbial oil production and rival plant-based fuels, the use of raw and waste materials as fermentation substrate is required. Starch is one of the most abundant carbohydrates in nature and it is constituted by glucose monomers. Y. lipolytica lacks the capacity to breakdown this polymer and thus expensive enzymatic and/or physical pre treatments are needed. RESULTS: In this work, we express heterologous alpha amylase and glucoamylase enzymes in Y. lipolytica. The modified strains were able to produce and secrete high amounts of active form of both proteins in the culture media. These strains were able to grow on starch as sole carbon source and produce certain amount of lipids. Thereafter, we expressed both enzymes in an engineered strain able to overaccumulate lipids. This strain was able to produce up to 21 % of DCW as fatty acids from soluble starch, 5.7 times more than the modified strain in the wild-type background. Media optimization to increase the C/N ratio to 90 increased total lipid content up to 27 % of DCW. We also tested these strains in industrial raw starch as a proof of concept of the feasibility of the consolidated bioprocess. Lipid production from raw starch was further enhanced by the expression of a second copy of each enzyme. Finally, we determined in silico that the properties of a biodiesel produced by this strain from raw starch would fit the established standards. CONCLUSIONS: In this work, we performed a strain engineering approach to obtain a consolidated bioprocess to directly produce biolipids from raw starch. Additionally, we proved that lipid production from starch can be enhanced by both metabolic engineering and culture condition optimization, setting up the basis for further studies. PMID- 26379780 TI - Effect of bupivacaine soaked gauze in postoperative pain relief in laparoscopic cholecystectomy: a prospective observational controlled trial in 120 patients. AB - BACKGROUND: Symptomatic gallstone disease is one of the most common problem attended by a general surgeon. The application of minimally invasive surgical techniques for the removal of gallbladder is now an accepted and preferred method for treating this condition. The avoidance of a subcostal incision and minimal bowel handling leads to decreased postoperative pain, early returning to function and overall shorter duration of hospital stay. Nevertheless, patients do have significant postoperative pain, and newer techniques to further reduce this pain are the subject of many ongoing studies. Many intraoperative techniques for reducing postoperative pain have been described. The current practice at many institutions, including ours, is to discharge the patient on the first postoperative day on oral analgesics. Better control of postoperative pain may help establishing laparoscopic cholecystectomy as a day care procedure in selected patients. The aim of this study is to determine the effect of 0.5 % bupivacaine soaked oxidized regenerated cellulose surgical versus normal saline soaked surgical applied at the gallbladder bed on postoperative mean pain score after laparoscopic cholecystectomy for symptomatic gallstones. PATIENTS AND METHODS: Patients scheduled for laparoscopic cholecystectomy were enrolled in the study after meeting the inclusion criteria. Relevant history was taken and clinical examination was done. Necessary investigations were carried out. All patients were divided to receive either 0.5 % bupivacaine soaked surgicel or normal saline soaked surgicel after laparoscopic cholecystectomy with each group having equal number of patients. The pain score was measured with a visual analogue scale (VAS) at 4, 12 and 24 h after the procedure in both groups. All data was recorded on performa and SPSS-19 was used for analysis. RESULTS: The demographic characteristic of the two groups has shown that studied patients were matched as regarding gender, age, weight, ASA status and duration of surgery. Post-operative abdominal pain was significantly lower in bupivacaine Group than Saline group. This difference was reported from 4 h till 12 h post-operatively. Bradycardia, Hypotension and Urinary retention were the most common perioperative symptoms reported, with an incidence of 28.3 % in the saline Group and 15 % in the bupivacaine group with no significant differences. Evaluation of postoperative details such as oral intake, time to walk and length of hospital stay revealed that bupivacaine group reported better outcomes as compared to saline group. CONCLUSION: Placing bupivacaine soaked surgicel has been shown to decrease the mean postoperative pain score in patients. No significant complication was noticed with the use of surgicel. Because adequate pain control requires intravenous medications, additional methods for pain control need to be studied before laparoscopic cholecystectomy can be routinely performed as a day care case. PMID- 26379781 TI - L(59) TGF-beta LAP degradation products serve as a promising blood biomarker for liver fibrogenesis in mice. AB - BACKGROUND: Hepatic fibrosis, which is the excessive accumulation of extracellular matrices (ECMs) produced mainly from activated hepatic stellate cells (HSCs), develops to cirrhosis over several decades. There are no validated biomarkers that can non-invasively monitor excessive production of ECM (i.e., fibrogenesis). Transforming growth factor (TGF)-beta, a key driver of fibrogenesis, is produced as an inactive latent complex, in which active TGF-beta is enveloped by its pro-peptide, the latency-associated protein (LAP). Thus, active TGF-beta must be released from the complex for binding to its receptor and inducing ECM synthesis. We recently reported that during the pathogenesis of liver fibrosis, plasma kallikrein (PLK) activates TGF-beta by cleavage between R(58) and L(59) residues within LAP and that one of its by-products, the N terminal side LAP degradation products ending at residue R(58) (R(58) LAP-DPs), can be detected mainly around activated HSCs by specific antibodies against R(58) cleavage edges and functions as a footprint of PLK-dependent TGF-beta activation. Here, we describe a sandwich enzyme-linked immunosorbent assay (ELISA) that detects the other by-products, the C-terminal side LAP-DPs starting from residue L(59) (L(59) LAP-DPs). We demonstrated that the L(59) LAP-DPs are a potentially novel blood biomarker reflecting hepatic fibrogenesis. RESULTS: We established a specific sandwich ELISA to quantify L(59) LAP-DPs as low as 2 pM and measured L(59) LAP-DP levels in the culture media of a human activated HSC line, TWNT-4 cells. L(59) LAP-DPs could be detected in their media, and after treatment of TWNT-4 cells with a TGF-beta receptor kinase inhibitor, SB431542, a simultaneous reduction was observed in both L(59) LAP-DP levels in the culture media and the mRNA expression levels of collagen type (I) alpha1. In carbon tetrachloride- and bile duct ligation-induced liver fibrosis models in mice, plasma L(59) LAP-DP levels increased prior to increase of hepatic hydroxyproline (HDP) contents and well correlated with alpha-smooth muscle actin (alphaSMA) expression in liver tissues. At this time, alphaSMA-positive cells as well as R(58) LAP-DPs were seen in their liver tissues. CONCLUSIONS: L(59) LAP-DPs reflect PLK-dependent TGF-beta activation and the increase in alphaSMA-positive activated HSCs in liver injury, thereby serving as a novel blood biomarker for liver fibrogenesis. PMID- 26379782 TI - RRegrs: an R package for computer-aided model selection with multiple regression models. AB - BACKGROUND: Predictive regression models can be created with many different modelling approaches. Choices need to be made for data set splitting, cross validation methods, specific regression parameters and best model criteria, as they all affect the accuracy and efficiency of the produced predictive models, and therefore, raising model reproducibility and comparison issues. Cheminformatics and bioinformatics are extensively using predictive modelling and exhibit a need for standardization of these methodologies in order to assist model selection and speed up the process of predictive model development. A tool accessible to all users, irrespectively of their statistical knowledge, would be valuable if it tests several simple and complex regression models and validation schemes, produce unified reports, and offer the option to be integrated into more extensive studies. Additionally, such methodology should be implemented as a free programming package, in order to be continuously adapted and redistributed by others. RESULTS: We propose an integrated framework for creating multiple regression models, called RRegrs. The tool offers the option of ten simple and complex regression methods combined with repeated 10-fold and leave-one-out cross validation. Methods include Multiple Linear regression, Generalized Linear Model with Stepwise Feature Selection, Partial Least Squares regression, Lasso regression, and Support Vector Machines Recursive Feature Elimination. The new framework is an automated fully validated procedure which produces standardized reports to quickly oversee the impact of choices in modelling algorithms and assess the model and cross-validation results. The methodology was implemented as an open source R package, available at https://www.github.com/enanomapper/RRegrs, by reusing and extending on the caret package. CONCLUSION: The universality of the new methodology is demonstrated using five standard data sets from different scientific fields. Its efficiency in cheminformatics and QSAR modelling is shown with three use cases: proteomics data for surface-modified gold nanoparticles, nano-metal oxides descriptor data, and molecular descriptors for acute aquatic toxicity data. The results show that for all data sets RRegrs reports models with equal or better performance for both training and test sets than those reported in the original publications. Its good performance as well as its adaptability in terms of parameter optimization could make RRegrs a popular framework to assist the initial exploration of predictive models, and with that, the design of more comprehensive in silico screening applications.Graphical abstractRRegrs is a computer-aided model selection framework for R multiple regression models; this is a fully validated procedure with application to QSAR modelling. PMID- 26379783 TI - The short-term effect of bariatric surgery on non-invasive markers of artery function in patients with metabolic syndrome. AB - BACKGROUND: An improved understanding of the vascular function, measured in non invasive way, in constantly growing group of patients at increased risk of cardiovascular events is necessary. To evaluate the effects of metabolic syndrome in morbidly obese patients and body mass reduction secondary to gastric bypass surgery on convenient and new non-invasive markers of artery function: pulse wave velocity (PWV), flow- and nitroglycerin-mediated dilatation (FMD, NTG). METHODS: There were 40 patients included into prospective study, who were qualified for bariatric surgery (OB1) and evaluated again 6 m after surgery (OB2). A control group (CG) consisted of 15 healthy women. A second control group (CG2) consisted of 15 women with grade 1 obesity. PWV, FMD, NTG were assessed. RESULTS: The reduction of BMI (kg/m(2)) from 47.73 +/- 6.18 (OB1) to 35.22 +/- 5.20 (OB2) was observed. The PWV turned out to be higher before bariatric surgery (OB1 vs. OB2 8.53 +/- 1.76 vs. 7.82 +/- 1.49 m/s; p < 0.001), however it was no different than PWV in CG. In OB1 group PWV showed correlation with age (r = 0.492, p = 0.001), HR (r = 0.324, p = 0.04), %FM (r = 0.328; p = 0.039), NTG% (r = -0.332, p = 0.036) as well as hsCRP (r = 0.394, p = 0.014). A multivariate analysis showed that the most significant factors influencing PWV were age (p = 0.0005) and hsCRP (p = 0.0014), pseudo R(2) index 0.44365. The values of FMD differed between OB1 and OB2 groups (12.83 +/- 5.15 vs. 17.52 +/- 5.50 %; p < 0.0001), however, they were similar to results obtained in CG (14.45 +/- 6.14 %; NS). The values of nitroglycerin-mediated dilatation differed between OB1 and OB2 groups (21.47 +/- 8.31 vs. 28.54 +/- 8.16 %; p < 0.0001) and were lower as compared with CG (31.42 +/- 5.95 %; p = 0.0005). CONCLUSION: Body mass reduction secondary to bariatric surgery in patients with severe obesity and metabolic syndrome results in improvement of functional markers of artery function and advantageous metabolic changes. The improvement in functional markers of artery function (NTG%) was correlated with change in triglyceride blood concentration. PMID- 26379784 TI - Assessment of Inflammation in an Acute on Chronic Model of Inflammatory Bowel Disease with Ultrasound Molecular Imaging. AB - BACKGROUND: Ultrasound (US) molecular imaging has shown promise in assessing inflammation in preclinical, murine models of inflammatory bowel disease. These models, however, initiated acute inflammation on previously normal colons, in contrast to patients where acute exacerbations are often in chronically inflamed regions. In this study, we explored the potential of dual P- and E-selectin targeted US imaging for assessing acute inflammation on a murine quiescent chronic inflammatory background. METHODS: Chronic colitis was induced using three cycles of 4% DSS in male FVB mice. Acute inflammation was initiated 2 weeks after the final DSS cycle through rectal administration of 1% TNBS. Mice at different stages of inflammation were imaged using a small animal ultrasound system following i.v. injection of microbubbles targeted to P- and E-selectin. In vivo imaging results were correlated with ex vivo immunofluorescence and histology. RESULTS: Induction of acute inflammation resulted in an increase in the targeted US signal from 5.5 +/- 5.1 arbitrary units (a.u.) at day 0 to 61.0 +/- 45.2 a.u. (P < 0.0001) at day 1, 36.3 +/- 33.1 a.u. at day 3, returning to levels similar to control at day 5. Immunofluorescence showed significant increase in the percentage of P- and E-selectin positive vessels at day 1 (P-selectin: 21.0 +/- 7.1% of vessels; P < 0.05; E-selectin: 16.4 +/-3.7%; P < 0.05) compared to day 0 (P-selectin: 10.3 +/- 5.7%; E-selectin: 7.3 +/- 7.0%). CONCLUSIONS: Acute inflammation can be accurately measured in a clinically relevant murine model of chronic IBD using ultrasound molecular imaging with a dual P- and E- selectin targeted contrast agent. PMID- 26379785 TI - Unmasking Silent Endothelial Activation in the Cardiovascular System Using Molecular Magnetic Resonance Imaging. AB - Endothelial activation is a hallmark of cardiovascular diseases, acting either as a cause or a consequence of organ injury. To date, we lack suitable methods to measure endothelial activation in vivo. In the present study, we developed a magnetic resonance imaging (MRI) method allowing non-invasive endothelial activation mapping in the vasculature of the main organs affected during cardiovascular diseases. In clinically relevant contexts in mice (including systemic inflammation, acute and chronic kidney diseases, diabetes mellitus and normal aging), we provided evidence that this method allows detecting endothelial activation before any clinical manifestation of organ failure in the brain, kidney and heart with an exceptional sensitivity. In particular, we demonstrated that diabetes mellitus induces chronic endothelial cells activation in the kidney and heart. Moreover, aged mice presented activated endothelial cells in the kidneys and the cerebrovasculature. Interestingly, depending on the underlying condition, the temporospatial patterns of endothelial activation in the vascular beds of the cardiovascular system were different. These results demonstrate the feasibility of detecting silent endothelial activation occurring in conditions associated with high cardiovascular risk using molecular MRI. PMID- 26379786 TI - A Disposable Microfluidic Device for Controlled Drug Release from Thermal Sensitive Liposomes by High Intensity Focused Ultrasound. AB - The drug release triggered thermally by high intensity focused ultrasound (HIFU) has been considered a promising drug delivery strategy due to its localized energy and non-invasive characters. However, the mechanism underlying the HIFU mediated drug delivery remains unclear due to its complexity at the cellular level. In this paper, micro-HIFU (MHIFU) generated by a microfluidic device is introduced which is able to control the drug release from temperature-sensitive liposomes (TSL) and evaluate the thermal and mechanical effects of ultrasound on the cellular drug uptake and apoptosis. By simply adjusting the input electrical signal to the device, the temperature of sample can be maintained at 37 degrees C, 42 degrees C and 50 degrees C with the deviation of +/- 0.3 degrees C as desired. The flow cytometry results show that the drug delivery under MHIFU sonication leads to a significant increase in apoptosis compared to the drug release by incubation alone at elevated temperature of 42 degrees C. Furthermore, increased squamous and protruding structures on the surface membrane of cells were detected by atomic force microscopy (AFM) after MHIFU irradiation of TSL. We demonstrate that compared to the routine HIFU treatment, MHIFU enables monitoring of in situ interactions between the ultrasound and cell in real time. Furthermore, it can quantitatively analyze and characterize the alterations of the cell membrane as a function of the treatment time. PMID- 26379787 TI - Identification of 7 Proteins in Sera of RA Patients with Potential to Predict ETA/MTX Treatment Response. AB - OBJECTIVE: The recent growth of innovating biologics has opened fascinating avenues for the management of patients. In rheumatoid arthritis, many biologics are currently available, the choice of which being mostly determined empirically. Importantly, a given biologic may not be active in a fraction of patients and may even provoke side effects. Here, we conducted a comparative proteomics study in attempt to identify a predictive theranostic signature of non-response in patients with rheumatoid arthritis treated by etanercept/methotrexate combination. METHODS: A serum sample was collected prior to treatment exposure from a cohort of 22 patients with active RA. A proteomic "label free" approach was then designed to quantitate protein biomarkers using mass spectrometry. To verify these results, a relative quantification followed by an absolute quantification of interesting protein candidates were performed on a second cohort. The criterion of judgment was the response to etanercept/methotrexate combination according to the EULAR criteria assessed at 6 months of treatment. RESULTS: These investigations led to the identification of a set of 12 biomarkers with capacity to predict treatment response. A targeted quantitative analysis allowed to confirm the potential of 7 proteins from the latter combination on a new cohort of 16 patients. Two highly discriminating proteins, PROS and CO7, were further evaluated by ELISA on this second cohort. By combining the concentration threshold of each protein associated to a right classification (responders vs non responders), the sensitivity and specificity reached 88.9 % and 100 %, respectively. CONCLUSION: Prior to methotrexate/etanercept treatment, abundance of several sera proteins, notably PROS and CO7, were associated to response status of RA patients 6 month after treatment initiation. PMID- 26379788 TI - Casein-Coated Fe5C2 Nanoparticles with Superior r2 Relaxivity for Liver-Specific Magnetic Resonance Imaging. AB - Iron oxide nanoparticles have been extensively used as T2 contrast agents for liver-specific magnetic resonance imaging (MRI). The applications, however, have been limited by their mediocre magnetism and r2 relaxivity. Recent studies show that Fe5C2 nanoparticles can be prepared by high temperature thermal decomposition. The resulting nanoparticles possess strong and air stable magnetism, suggesting their potential as a novel type of T2 contrast agent. To this end, we improve the synthetic and surface modification methods of Fe5C2 nanoparticles, and investigated the impact of size and coating on their performances for liver MRI. Specifically, we prepared 5, 14, and 22 nm Fe5C2 nanoparticles and engineered their surface by: 1) ligand addition with phospholipids, 2) ligand exchange with zwitterion-dopamine-sulfonate (ZDS), and 3) protein adsorption with casein. It was found that the size and surface coating have varied levels of impact on the particles' hydrodynamic size, viability, uptake by macrophages, and r2 relaxivity. Interestingly, while phospholipid- and ZDS-coated Fe5C2 nanoparticles showed comparable r2, the casein coating led to an r2 enhancement by more than 2 fold. In particular, casein coated 22 nm Fe5C2 nanoparticle show a striking r2 of 973 mM(-1)s(-1), which is one of the highest among all of the T2 contrast agents reported to date. Small animal studies confirmed the advantage of Fe5C2 nanoparticles over iron oxide nanoparticles in inducing hypointensities on T2-weighted MR images, and the particles caused little toxicity to the host. The improvements are important for transforming Fe5C2 nanoparticles into a new class of MRI contrast agents. The observations also shed light on protein-based surface modification as a means to modulate contrast ability of magnetic nanoparticles. PMID- 26379789 TI - Targeted Mesoporous Iron Oxide Nanoparticles-Encapsulated Perfluorohexane and a Hydrophobic Drug for Deep Tumor Penetration and Therapy. AB - A magneto-responsive energy/drug carrier that enhances deep tumor penetration with a porous nano-composite is constructed by using a tumor-targeted lactoferrin (Lf) bio-gate as a cap on mesoporous iron oxide nanoparticles (MIONs). With a large payload of a gas-generated molecule, perfluorohexane (PFH), and a hydrophobic anti-cancer drug, paclitaxel (PTX), Lf-MIONs can simultaneously perform bursting gas generation and on-demand drug release upon high-frequency magnetic field (MF) exposure. Biocompatible PFH was chosen and encapsulated in MIONs due to its favorable phase transition temperature (56 degrees C) and its hydrophobicity. After a short-duration MF treatment induces heat generation, the local pressure increase via the gasifying of the PFH embedded in MION can substantially rupture the three-dimensional tumor spheroids in vitro as well as enhance drug and carrier penetration. As the MF treatment duration increases, Lf MIONs entering the tumor spheroids provide an intense heat and burst-like drug release, leading to superior drug delivery and deep tumor thermo-chemo-therapy. With their high efficiency for targeting tumors, Lf-MIONs/PTX-PFH suppressed subcutaneous tumors in 16 days after a single MF exposure. This work presents the first study of using MF-induced PFH gasification as a deep tumor-penetrating agent for drug delivery. PMID- 26379791 TI - Biomimetic Acoustically-Responsive Vesicles for Theranostic Applications. AB - In recent years, biomimetic cell membrane-derived particles have emerged as a new class of drug delivery system with advantages of biocompatibility, ease of isolation and long circulation profile. Here we report the development and potential theranostic applications of a new biomimetic acoustically-responsive droplet system derived from mammalian red blood cell membrane (RBCM). We hypothesized that drug-loaded RBCM droplets (RBCMDs) would undergo a transition from liquid (droplets) to gas (bubbles) upon high intensity focused ultrasound (HIFU) insonation, resulting in on-demand drug release. The generated microbubbles could also serve as a contrast agent to enhance ultrasound imaging. As-synthesized RBCMDs exhibited uniform size, good dispersity and preservation of RBCM-associated proteins that prevented uptake by macrophages. Camptothecin (CPT), an anti-cancer drug, was successfully loaded in the RBCMDs with a loading efficiency of 2-3% and an encapsulation efficiency of 62-97%. A short (3 min) exposure to HIFU irradiation triggered release of CPT from the RBCMDs and the physical explosion of droplets damaged nearby cancer cells resulting in significant cell death. In addition, the acoustically vaporized RBCMDs significantly increased the ultrasound echo signal to 30 dB. Lastly, we demonstrated that RBCMDs could be acoustically vaporized in vivo in target tissues, and enhancing ultrasound imaging. Taken together, we have developed a new class of naturally derived RBCMDs which show great potential for future application in remotely triggered drug delivery and ultrasound imaging enhancement. PMID- 26379792 TI - Zigzag Generalized Levy Walk: the In Vivo Search Strategy of Immunocytes. AB - Immune responses are based on the coordinated searching behaviors of immunocytes that are aimed at tracking down specific targets. The search efficiency of immunocytes significantly affects the speed of initiation and development of immune responses. Previous studies have shown that not only the intermittent walk but also the zigzag turning preference of immunocytes contributes to the search efficiency. However, among existing models describing immunocytes' search strategy, none has captured both features. Here we propose a zigzag generalized Levy walk model to describe the search strategy of immunocytes more accurately and comprehensively by considering both the intermittent and the zigzag-turning walk features. Based on the analysis of the searching behaviors of typical immune cell types, dendritic cells and leukocytes, in their native physiological environment, we demonstrate that the model can describe the in vivo search strategy of immunocytes well. Furthermore, by analyzing the search efficiency, we find that this type of search strategy enables immunocytes to capture rare targets in approximately half the time than the previously proposed generalized Levy walk. This study sheds new light on the fundamental mechanisms that drive the efficient initiation and development of immune responses and in turn may lead to the development of novel therapeutic approaches for diseases ranging from infection to cancer. PMID- 26379790 TI - Magnetic Nanoparticles in Cancer Theranostics. AB - In a report from 2008, The International Agency for Research on Cancer predicted a tripled cancer incidence from 1975, projecting a possible 13-17 million cancer deaths worldwide by 2030. While new treatments are evolving and reaching approval for different cancer types, the main prevention of cancer mortality is through early diagnosis, detection and treatment of malignant cell growth. The last decades have seen a development of new imaging techniques now in widespread clinical use. The development of nano-imaging through fluorescent imaging and magnetic resonance imaging (MRI) has the potential to detect and diagnose cancer at an earlier stage than with current imaging methods. The characteristic properties of nanoparticles result in their theranostic potential allowing for simultaneous detection of and treatment of the disease. This review provides state of the art of the nanotechnological applications for cancer therapy. Furthermore, it advances a novel concept of personalized nanomedical theranostic therapy using iron oxide magnetic nanoparticles in conjunction with MRI imaging. Regulatory and industrial perspectives are also included to outline future perspectives in nanotechnological cancer research. PMID- 26379793 TI - CO2 bubbling-based 'Nanobomb' System for Targetedly Suppressing Panc-1 Pancreatic Tumor via Low Intensity Ultrasound-activated Inertial Cavitation. AB - Noninvasive and targeted physical treatment is still desirable especially for those cancerous patients. Herein, we develop a new physical treatment protocol by employing CO2 bubbling-based 'nanobomb' system consisting of low-intensity ultrasound (1.0 W/cm(2)) and a well-constructed pH/temperature dual-responsive CO2 release system. Depending on the temperature elevation caused by exogenous low-intensity therapeutic ultrasound irradiation and the low pH caused by the endogenous acidic-environment around/within tumor, dual-responsive CO2 release system can quickly release CO2 bubbles, and afterwards, the generated CO2 bubbles waves will timely explode before dissolution due to triggering by therapeutic ultrasound waves. Related bio-effects (e.g., cavitation, mechanical, shock waves, etc) caused by CO2 bubbles' explosion effectively induce instant necrosis of panc 1 cells and blood vessel destruction within panc-1 tumor, and consequently inhibit the growth of panc-1 solid tumor, simultaneously minimizing the side effects to normal organs. This new physiotherapy employing CO2 bubbling-based 'nanobomb' system promises significant potentials in targetedly suppressing tumors, especially for those highly deadly cancers. PMID- 26379794 TI - Anxiety-like behavior in Rett syndrome: characteristics and assessment by anxiety scales. AB - BACKGROUND: Rett syndrome (RTT) is a severe neurodevelopmental disorder characterized by regression of language and motor skills, cognitive impairment, and frequent seizures. Although the diagnostic criteria focus on communication, motor impairments, and hand stereotypies, behavioral abnormalities are a prevalent and disabling component of the RTT phenotype. Among these problematic behaviors, anxiety is a prominent symptom. While the introduction of the Rett Syndrome Behavioral Questionnaire (RSBQ) represented a major advancement in the field, no systematic characterization of anxious behavior using the RSBQ or other standardized measures has been reported. METHODS: This study examined the profiles of anxious behavior in a sample of 74 girls with RTT, with a focus on identifying the instrument with the best psychometric properties in this population. The parent-rated RSBQ, Anxiety, Depression, and Mood Scale (ADAMS), and Aberrant Behavior Checklist-Community (ABC-C), two instruments previously employed in children with neurodevelopmental disorders, were analyzed in terms of score profiles, relationship with age and clinical severity, reliability, concurrent validity, and functional implications. The latter were determined by regression analyses with the Vineland Adaptive Behavior Scales-Second Edition (Vineland-II) and the Child Health Questionnaire (CHQ), a quality of life measure validated in RTT. RESULTS: We found that scores on anxiety subscales were intermediate in range with respect to other behavioral constructs measured by the RSBQ, ADAMS, and ABC-C. Age did not affect scores, and severity of general anxiety was inversely correlated with clinical severity. We demonstrated that the internal consistency of the anxiety-related subscales were among the highest. Test-retest and intra-rater reliability was superior for the ADAMS subscales. Convergent and discriminant validity were measured by inter-scale correlations, which showed the best profile for the social anxiety subscales. Of these, only the ADAMS Social Avoidance showed correlation with quality of life. CONCLUSIONS: We conclude that anxiety-like behavior is a prominent component of RTT's behavioral phenotype, which affects predominantly children with less severe neurologic impairment and has functional consequences. Based on available data on standardized instruments, the ADAMS and in particular its Social Avoidance subscale has the best psychometric properties and functional correlates that make it suitable for clinical and research applications. PMID- 26379795 TI - Disciplined Improvisation: Characteristics of Inquiry in Mindfulness-Based Teaching. AB - Evidence for the effectiveness of mindfulness-based stress reduction (MBSR) and mindfulness-based cognitive therapy (MBCT) is rapidly growing as interest in this field expands. By contrast, there are few empirical analyses of the pedagogy of MBSR and MBCT. Development of the evidence base concerning the teaching of MBCT or MBSR would support the integrity of the approach in the context of rapid expansion. This paper describes an applied conversation analysis (CA) of the characteristics of inquiry in the MBSR and MBCT teaching process. Audio recordings of three 8-week MBCT and MBSR classes, with 24, 12, and 6 participants, were transcribed and systematically examined. The study focused on the teacher-led interactive inquiry which takes place in each session after a guided meditation practice. The study describes and analyzes three practices within the inquiry process that can be identified in sequences of talk: turn taking talk involving questions and reformulations; the development of participant skills in a particular way of describing experience; and talk that constructs intersubjective connection and affiliation within the group. CA enables fine-grained analysis of the interactional work of mindfulness-based inquiry. Inquiry is a process of disciplined improvisation which is both highly specific to the conditions of the moment it took place in and uses repeated and recognizable patterns of interaction. PMID- 26379796 TI - Some Reflections on Being Good, on not Being Good and on Just Being. PMID- 26379798 TI - Teaching computational neuroscience. AB - The problems and beauty of teaching computational neuroscience are discussed by reviewing three new textbooks. PMID- 26379797 TI - Information processing in the CNS: a supramolecular chemistry? AB - How does central nervous system process information? Current theories are based on two tenets: (a) information is transmitted by action potentials, the language by which neurons communicate with each other-and (b) homogeneous neuronal assemblies of cortical circuits operate on these neuronal messages where the operations are characterized by the intrinsic connectivity among neuronal populations. In this view, the size and time course of any spike is stereotypic and the information is restricted to the temporal sequence of the spikes; namely, the "neural code". However, an increasing amount of novel data point towards an alternative hypothesis: (a) the role of neural code in information processing is overemphasized. Instead of simply passing messages, action potentials play a role in dynamic coordination at multiple spatial and temporal scales, establishing network interactions across several levels of a hierarchical modular architecture, modulating and regulating the propagation of neuronal messages. (b) Information is processed at all levels of neuronal infrastructure from macromolecules to population dynamics. For example, intra-neuronal (changes in protein conformation, concentration and synthesis) and extra-neuronal factors (extracellular proteolysis, substrate patterning, myelin plasticity, microbes, metabolic status) can have a profound effect on neuronal computations. This means molecular message passing may have cognitive connotations. This essay introduces the concept of "supramolecular chemistry", involving the storage of information at the molecular level and its retrieval, transfer and processing at the supramolecular level, through transitory non-covalent molecular processes that are self-organized, self-assembled and dynamic. Finally, we note that the cortex comprises extremely heterogeneous cells, with distinct regional variations, macromolecular assembly, receptor repertoire and intrinsic microcircuitry. This suggests that every neuron (or group of neurons) embodies different molecular information that hands an operational effect on neuronal computation. PMID- 26379799 TI - Phase reset affects auditory-visual simultaneity judgment. AB - We continuously receive the external information from multiple sensors simultaneously. The brain must judge a source event of these sensory informations and integrate them. It is thought that judging the simultaneity of such multisensory stimuli is an important cue when we discriminate whether the stimuli are derived from one event or not. Although previous studies have investigated the correspondence between an auditory-visual (AV) simultaneity perceptions and the neural responses, there are still few studies of this. Electrophysiological studies have reported that ongoing oscillations in human cortex affect perception. Especially, the phase resetting of ongoing oscillations has been examined as it plays an important role in multisensory integration. The aim of this study was to investigate the relationship of phase resetting for the judgment of AV simultaneity judgement tasks. The subjects were successively presented with auditory and visual stimuli with intervals that were controlled as [Formula: see text] and they were asked to report whether they perceived them simultaneously or not. We investigated the effects of the phase of ongoing oscillations on simultaneity judgments with AV stimuli with SOAs in which the detection rate of asynchrony was 50 %. It was found that phase resetting at the beta frequency band in the brain area that related to the modality of the following stimulus occurred after preceding stimulus onset only when the subjects perceived AV stimuli as simultaneous. This result suggested that beta phase resetting occurred in areas that are related to the subsequent stimulus, supporting perception multisensory stimuli as simultaneous. PMID- 26379800 TI - Localization of neural efficiency of the mathematically gifted brain through a feature subset selection method. AB - Based on the neural efficiency hypothesis and task-induced EEG gamma-band response (GBR), this study investigated the brain regions where neural resource could be most efficiently recruited by the math-gifted adolescents in response to varying cognitive demands. In this experiment, various GBR-based mental states were generated with three factors (level of mathematical ability, task complexity, and short-term learning) modulating the level of neural activation. A feature subset selection method based on the sequential forward floating search algorithm was used to identify an "optimal" combination of EEG channel locations, where the corresponding GBR feature subset could obtain the highest accuracy in discriminating pairwise mental states influenced by each experiment factor. The integrative results from multi-factor selections suggest that the right-lateral fronto-parietal system is highly involved in neural efficiency of the math-gifted brain, primarily including the bilateral superior frontal, right inferior frontal, right-lateral central and right temporal regions. By means of the localization method based on single-trial classification of mental states, new GBR features and EEG channel-based brain regions related to mathematical giftedness were identified, which could be useful for the brain function improvement of children/adolescents in mathematical learning through brain computer interface systems. PMID- 26379801 TI - Evaluation of local field potential signals in decoding of visual attention. AB - In the field of brain research, attention as one of the main issues in cognitive neuroscience is an important mechanism to be studied. The complicated structure of the brain cannot process all the information it receives at any moment. Attention, in fact, is considered as a possible useful mechanism in which brain concentrates on the processing of important information which is required at any certain moment. The main goal of this study is decoding the location of visual attention from local field potential signals recorded from medial temporal (MT) area of a macaque monkey. To this end, feature extraction and feature selection are applied in both the time and the frequency domains. After applying feature extraction methods such as the short time Fourier transform, continuous wavelet transform (CWT), and wavelet energy (scalogram), feature selection methods are evaluated. Feature selection methods used here are T-test, Entropy, receiver operating characteristic, and Bhattacharyya. Subsequently, different classifiers are utilized in order to decode the location of visual attention. At last, the performances of the employed classifiers are compared. The results show that the maximum information about the visual attention in area MT exists in the low frequency features. Interestingly, low frequency features over all the time-axis and all of the frequency features at the initial time interval in the spectrogram domain contain the most valuable information related to the decoding of spatial attention. In the CWT and scalogram domains, this information exists in the low frequency features at the initial time interval. Furthermore, high performances are obtained for these features in both the time and the frequency domains. Among different employed classifiers, the best achieved performance which is about 84.5 % belongs to the K-nearest neighbor classifier combined with the T-test method for feature selection in the time domain. Additionally, the best achieved result (82.9 %) is related to the spectrogram with the least number of selected features as large as 200 features using the T-test method and SVM classifier in the time frequency domain. PMID- 26379802 TI - Modeling spatial-temporal operations with context-dependent associative memories. AB - We organize our behavior and store structured information with many procedures that require the coding of spatial and temporal order in specific neural modules. In the simplest cases, spatial and temporal relations are condensed in prepositions like "below" and "above", "behind" and "in front of", or "before" and "after", etc. Neural operators lie beneath these words, sharing some similarities with logical gates that compute spatial and temporal asymmetric relations. We show how these operators can be modeled by means of neural matrix memories acting on Kronecker tensor products of vectors. The complexity of these memories is further enhanced by their ability to store episodes unfolding in space and time. How does the brain scale up from the raw plasticity of contingent episodic memories to the apparent stable connectivity of large neural networks? We clarify this transition by analyzing a model that flexibly codes episodic spatial and temporal structures into contextual markers capable of linking different memory modules. PMID- 26379803 TI - Stochastic S-system modeling of gene regulatory network. AB - Microarray gene expression data can provide insights into biological processes at a system-wide level and is commonly used for reverse engineering gene regulatory networks (GRN). Due to the amalgamation of noise from different sources, microarray expression profiles become inherently noisy leading to significant impact on the GRN reconstruction process. Microarray replicates (both biological and technical), generated to increase the reliability of data obtained under noisy conditions, have limited influence in enhancing the accuracy of reconstruction . Therefore, instead of the conventional GRN modeling approaches which are deterministic, stochastic techniques are becoming increasingly necessary for inferring GRN from noisy microarray data. In this paper, we propose a new stochastic GRN model by investigating incorporation of various standard noise measurements in the deterministic S-system model. Experimental evaluations performed for varying sizes of synthetic network, representing different stochastic processes, demonstrate the effect of noise on the accuracy of genetic network modeling and the significance of stochastic modeling for GRN reconstruction . The proposed stochastic model is subsequently applied to infer the regulations among genes in two real life networks: (1) the well-studied IRMA network, a real-life in-vivo synthetic network constructed within the Saccharomyces cerevisiae yeast, and (2) the SOS DNA repair network in Escherichia coli. PMID- 26379804 TI - Power-rate synchronization of coupled genetic oscillators with unbounded time varying delay. AB - In this paper, a new synchronization problem for the collective dynamics among genetic oscillators with unbounded time-varying delay is investigated. The dynamical system under consideration consists of an array of linearly coupled identical genetic oscillators with each oscillators having unbounded time-delays. A new concept called power-rate synchronization, which is different from both the asymptotical synchronization and the exponential synchronization, is put forward to facilitate handling the unbounded time-varying delays. By using a combination of the Lyapunov functional method, matrix inequality techniques and properties of Kronecker product, we derive several sufficient conditions that ensure the coupled genetic oscillators to be power-rate synchronized. The criteria obtained in this paper are in the form of matrix inequalities. Illustrative example is presented to show the effectiveness of the obtained results. PMID- 26379805 TI - Strategic aspects of higher education reform to cultivate specialists in diagnostic and biopharma industry as applicable to Predictive, Preventive and Personalized Medicine as the Medicine of the Future. AB - Predictive, Preventive and Personalized Medicine as the Medicine of the Future represents an innovative model for advanced healthcare and robust platform for relevant industrial branches for diagnostics and pharmaceutics. However, rapid market penetration of new medicines and technologies demands the implementation of reforms not only in the spheres of biopharmaceutical industries and healthcare, but also in education. Therefore, the problem of the fundamental, modern preparation of specialists in bioengineering and affiliated fields is becoming particularly urgent, and it requires significant revision of training programs of higher education practice into current medical universities. Modernization and integration of widely accepted medical and teaching standards require consolidation of both the natural sciences and medical sciences that may become the conceptual basis for a university medical education. The main goal of this training is not simply to achieve advanced training and expansion of technological skills, but to provide development of novel multifaceted approaches to build academic schools for future generations. PMID- 26379806 TI - In Response to the Article "Usefulness of Ultrasound Examinations in the Diagnostics of Necrotizing Enterocolitis". Pol J Radiol, 2015; 80: 1-9. PMID- 26379807 TI - Hippocampal Changes in Febrile Infection-Related Epilepsy Syndrome (FIRES). AB - BACKGROUND: Febrile seizures are the most common seizure disorder in childhood, associated with a significant rise in body temperature. However, post-infectious refractory afebrile form of seizures in previously healthy children is being increasingly recognized in around the world, which evolves into a chronic refractory form of epilepsy. The term 'Febrile infection-related epilepsy syndrome' (FIRES) has been proposed for these conditions and represents a refractory severe post-infectious epileptic condition in previously normal children. CASE REPORT: We report the initial and follow-up MR imaging findings in a 5year-old with refractory epilepsy post-febrile seizures. CONCLUSIONS: In summary, acute post-infectious seizures are increasingly being recognized across the globe with the newly coined term 'Febrile infection-related epilepsy syndrome'(FIRES) for this group of immune-mediated epileptic encephalopathy in previously healthy children. This has three phases: episode of simple febrile infection, followed by acute refractory seizures and lastly the chronic phase of neuropsychological impairments and seizures. PMID- 26379808 TI - Congenital Epulis: A Rare Benign Jaw Tumour in a 2-Day-Old Male Baby. AB - BACKGROUND: Congenital epulis is a rare benign jaw tumor. It is a reactive or degenerative lesion having a mesenchymal origin; presenting as an obvious mass arising from the gingival mucosa of the maxilla or mandible, presenting in neonates. Its etiology, histopathogenesis and natural history are still not well established. It is seen usually in the female gender and mostly involves the maxillary alveolar ridge. MATERIAL/MEHODS: We report a case of a 2.7 kg male baby born with growth on his mandibular ridge which was excised and was proved to be epulis on histopathology. RESULTS: Congenital epulis is often misdiagnosed before surgery because of its rarity and a lack of awareness of the condition by clinicians. It is important for the attending pediatricians, pediatric surgeon to be aware of this rare but benign congenital tumor. CONCLUSIONS: Congenital epulis is often misdiagnosed before surgery because of its rarity and a lack of awareness of the condition by clinicians. As the clinical presentation of this congenital tumor can be distressing due to its size and aggressive appearance, it is important for the attending pediatricians, pediatric surgeon to be aware of this rare but benign congenital tumor. PMID- 26379809 TI - Gangliocapsular Bleed with Ipsilateral Internal Carotid Artery Aplasia. AB - BACKGROUND: Agenesis requires an extensive work-up as a number of associated other vascular and nonvascular anomalies can be expected. In this scenario, an associated ipsilateral basal ganglia bleeding with subarachnoid haemorrhage with no aetiology is uncommon. We present such a case of moderate ipsilateral ganglio capsular bleed of unknown cause with associate aortic arch vessel anomaly. CASE REPORT: A 45-year-old diabetic man of Indian origin with complaints of a sudden onset of giddiness, left-sided weakness and slurring of speech. Motor system examination revealed power of grade 2. Computed tomography scan revealed a moderate bleeding in the basal ganglia and the right temporo-parietal lobe. Angiography revealed unilateral aplasia of the internal carotid artery. Patient improved symptomatically with a motor system power of grade 4 after hematoma evacuation and treatment with antibiotics, anti-edema measures and neuroprotective drugs. CONCLUSIONS: Developmental anomalies of the carotid and aortic arch with intracranial bleeding is a rare occurrence and any arterial anomaly requires extensive evaluation. PMID- 26379810 TI - Mitral Valve Clip for Treatment of Mitral Regurgitation: An Evidence-Based Analysis. AB - BACKGROUND: Many of the 500,000 North American patients with chronic mitral regurgitation may be poor candidates for mitral valve surgery. OBJECTIVE: The objective of this study was to investigate the comparative effectiveness, harms, and cost-effectiveness of percutaneous mitral valve repair using mitral valve clips in candidates at prohibitive risk for surgery. DATA SOURCES: We searched articles in MEDLINE, Embase, and the Cochrane Library published from 1994 to February 2014 for evidence of effectiveness and harms; for economic literature we also searched NHS EED and Tufts CEA registry. Grey literature was also searched. REVIEW METHODS: Primary studies were sought from existing systematic reviews that had employed reliable search and screening methods. Newer studies were sought by searching the period subsequent to the last search date of the review. Two reviewers screened records and assessed study validity. We used the Cochrane risk of bias tool for randomized, generic assessment for non-randomized studies, and the Phillips checklist for economic studies. RESULTS: Ten studies including 1 randomized trial were included. The majority of the direct comparative evidence compared the mitral valve clip repair with surgery in patients not particularly at prohibitive surgical risk. Irrespective of degenerative or functional chronic mitral regurgitation etiology, evidence of effectiveness and harms is inconclusive and of very low quality. Very-low-quality evidence indicates that percutaneous mitral valve clip repair may provide a survival advantage, at least during the first 1 to 2 years, particularly in medically managed chronic functional mitral regurgitation. Because of limitations in the design of studies, the cost-effectiveness of mitral valve clips in patients at prohibitive risk for surgery also could not be established. LIMITATIONS: Because of serious concerns of risk of bias, indirectness, and imprecision, evidence is of very low quality. CONCLUSIONS: No meaningful conclusions can be drawn about the comparative effectiveness, harms, and cost-effectiveness of mitral valve clips in the population with chronic mitral regurgitation who are at prohibitive risk for surgery. PMID- 26379811 TI - Recruitment and retention of women in fishing communities in HIV prevention research. AB - INTRODUCTION: Women in fishing communities in Uganda are more at risk and have higher rates of HIV infection. Socio-cultural gender norms, limited access to health information and services, economic disempowerment, sexual abuse and their biological susceptibility make women more at risk of infection. There is need to design interventions that cater for women's vulnerability. We explore factors affecting recruitment and retention of women from fishing communities in HIV prevention research. METHODS: An HIV incidence cohort screened 2074 volunteers (1057 men and 1017 women) aged 13-49 years from 5 fishing communities along Lake Victoria using demographic, medical history, risk behaviour assessment questionnaires.1000 HIV negative high risk volunteers were enrolled and followed every 6 months for 18 months. Factors associated with completion of study visits among women were analyzed using multivariable logistic regression. RESULTS: Women constituted 1,017(49%) of those screened, and 449(45%) of those enrolled with a median (IQR) age of 27 (22-33) years. Main reasons for non-enrolment were HIV infection (33.9%) and reported low risk behaviour (37.5%). A total of 382 (74%) women and 332 (69%) men completed all follow up visits. Older women (>24 yrs) and those unemployed, who had lived in the community for 5 years or more, were more likely to complete all study visits. CONCLUSION: Women had better retention rates than men at 18 months. Strategies for recruiting and retaining younger women and those who have stayed for less than 5 years need to be developed for improved retention of women in fishing communities in HIV prevention and research Programs. PMID- 26379812 TI - [Trali or acute post-transfusion pulmonary edema: report of a case with review of the literature]. PMID- 26379813 TI - Perception and Action in Teleoperated Needle Insertion. AB - We studied the effect of delay on perception and action in contact with a force field that emulates elastic soft tissue with a rigid nonlinear boundary. Such a field is similar to forces exerted on a needle during teleoperated needle insertion. We found that delay causes motor underestimation of the stiffness of this nonlinear soft tissue, without perceptual change. These experimental results are supported by simulation of a simplified mechanical model of the arm and neural controller, and a model for perception of stiffness, which is based on regression in the force-position space. In addition, we show that changing the gain of the teleoperation channel cancels the motor effect of delay without adding perceptual distortion. We conclude that it is possible to achieve perceptual and motor transparency in virtual one-dimensional remote needle insertion task. PMID- 26379814 TI - Prognostic value of Caspase-3 expression in cancers of digestive tract: a meta analysis and systematic review. AB - Various studies have evaluated the relationship between Caspase-3 expression and cancers of digestive tract. However, the prognostic value of Caspase-3 expression remains unclear. Hence, a meta-analysis was conducted with eligible studies which quantitatively evaluated the relationship between Caspase-3 expression and survival of patients in gastrointestinal tract cancers. Electronic databases updated to April 12(th), 2015 were searched to obtain relevant primary articles. Twelve studies were finally included with 2402 patients of esophageal, gastric or colorectal cancers. The detection of Caspase-3 was performed by immunohistochemistry (IHC). Survival data were aggregated and quantitatively analyzed. Combined hazard ratios (HRs) suggested that Caspase-3 expression had no specific impact on the overall survival (OS) (HR=0.94, 95% CI (0.64-1.37), I(2)=79.6%, P<0.001) of cancers of digestive tract. When each subtype of gastrointestinal cancer was analyzed separately, the over-expression of Caspase-3 was associated with favorable prognosis of OS in esophageal cancer HR=0.31, 95% CI (0.09-1.09), I(2)=54.6%, P=0.138). On the contrary, high level of Caspase-3 was correlated with poor prognosis of OS in gastric cancer HR=1.53, 95% CI (0.93 2.50), I(2)=46.4%, P=0.172). However, the expression of Caspase-3 showed no relationship of OS for patients with colorectal cancer (HR=1.03, 95% CI (0.66 1.63), I(2)=0.0%, P=0.410). Furthermore, the Caspase-3 expression was an indicator of poor prognosis of recurrence-free survival (RFS) for digestive tract cancer (HR=1.65, 95% CI (1.12-2.41), I(2)=43.9%, P=0.148). More studies need to be carried out to certify the prognostic value of Caspase-3 expression for patients with digestive tract cancers. PMID- 26379815 TI - Clinicopathological and prognostic significance of high Ki-67 labeling index in hepatocellular carcinoma patients: a meta-analysis. AB - BACKGROUND: The relationship between Ki-67 labeling index (LI) and clinical outcome in hepatocellular carcinoma (HCC) has been investigated by various studies, but no consistent result has been concluded. To define the prognostic significance of Ki-67 LI in patients with HCC, we performed a meta-analysis. METHODS: We searched for literatures in the following databases: PubMed, ISI Web of Science, EMBASE, Cochrane Central Register of Controlled Trials, Science Direct, Wiley Online Library, Google Scholar, China National Knowledge Infrastructure (CNKI), Chinese VIP and WanFang Databases. Our search ended on April 6th, 2015. Data were extracted from eligible studies and the correlation between Ki-67 LI and clinicopathological features of HCC was analyzed and pooled hazard ratios (HRs) for eligible studies were calculated by STATA 11.0 (STATA Corp., College, TX). RESULTS: In total, 54 studies involving 4996 patients were included in the current meta-analysis. The meta-analysis provided evidence that high Ki-67 LI was closely associated with histological grade, tumor size, number of tumor nodes, the status of metastasis, cirrhosis and vein invasion in HCC patients. The pooled HRs showed that high Ki-67 LI had an unfavorable impact on disease-free survival (DFS) (HR=1.626, 95% confidence interval (CI): 1.364-1.939, P<0.001), relapse-free survival (RFS) (HR=1.820, 95% CI: 1.215-2.725, P=0.004) and overall survival (OS) (HR=1.170, 95% CI: 1.102-1.243, P<0.001), respectively. Additionally, subgroup analysis indicated that high Ki-67 LI was related to poorer DFS, RFS and OS independent of regions, treatment strategies or statistical methods, except that no statistical significance was found on RFS (HR=2.413, 95% CI: 0.523-11.142, P=0.259) and OS (HR=1.998, 95% CI: 0.797-5.009, P=0.14) in patients with liver transplantation. CONCLUSIONS: Our meta-analysis suggests that higher Ki-67 LI confers a fast progression and poor prognosis for HCC patients. PMID- 26379816 TI - DNA repair gene ERCC1 polymorphisms and glioma susceptibility among Chinese population: a meta-analysis. AB - BACKGROUND: Excision repair cross complementation group 1 (ERCC1) has been shown to be involved in the progression of glioma susceptibility. However, the results remain conflict. The aim of this study was to systematically review and evaluate the role of ERCC1 C118T and C8092A polymorphisms in glioma risk among Chinese population. METHODS: Related case-control studies were searched in online electronic databases. Odds ratio (OR) with its 95% confidence interval (CI) were employed to calculate the extracted data. RESULTS: Total seven articles were retrieved, including 4426 subjects (1926 were glioma patients and 2500 were matched controls). No significant heterogeneity was found between studies (I(2)=0%, P>0.01). Our results demonstrated that A allele and AA genotype of ERCC1 C8092A polymorphism have a positive association with increasing the risk of glioma in the fixed-effect model (A vs. C: OR=1.13, 95% CI=1.02-1.25, P=0.02; AA vs. CC: OR=1.29, 95% CI=1.04-1.61, P=0.02; AA vs. CA+CC: OR=1.25, 95% CI=1.01 1.55, P=0.04). However, no significant relationship was found between C118T variant and glioma susceptibility. CONCLUSIONS: Our results indicated that ERCC1 C8092A, not C118T polymorphism might be a biomarker for patients with glioma among Chinese population. Future studies with more ethnicities are needed to explore the precise association. PMID- 26379817 TI - Meta-analysis of Huangqi injection for the adjunctive therapy of aplastic anemia. AB - Aplastic anemia therapy remains difficult, due to lack of effective treatment regimens. In recent years, Huangqi injection for the adjunctive therapy of aplastic anemia has been reported in many clinical trials. Considering that Huangqi injection may be a novel approach to aplastic anemia treatment, we conducted a meta-analysis of clinical controlled trials to assess the clinical value of Huangqi injection in the treatment of aplastic anemia. We searched the Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Full-text Database (VIP), Wanfang Database, PubMed and EMBASE database to collect the data about the trials of Huangqi injection combined with androgens for treating aplastic anemia. A total of ten studies involving 720 patients with aplastic anemia were included in this study. The meta-analysis showed significant increases in the pool effectiveness rate, white blood cells (WBC), haematoglobin (Hb), platelets (PLT), and reticulocytes (Ret) between the experimental group versus the control group. No severe side effects were found in this study. However, the lower Jadad scores and asymmetric funnel plot degrades the validity of the meta-analysis as the clinical evidence. Therefore, Huangqi injection may significantly enhance the efficacy of androgens for aplastic anemia, suggesting that the novel approach of Chinese traditional medicine combined with Western medicine is promising. The exact outcome required confirmation with rigorously well-designed multi-center trials. PMID- 26379818 TI - Efficacy and safety of landiolol for prevention of atrial fibrillation after cardiac surgery: a meta-analysis of randomized controlled trials. AB - Atrial fibrillation (AF) is a quite common complication during the postoperative period after cardiac surgery. Increasing studies have reported that landiolol may be effective in prevention of AF after cardiac surgery. Its efficacy and safety are seldom explored; hence we conducted a meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy and safety of landiolol in prevention of AF after cardiac surgery. Databases of PubMed, Embase and Cochrane Central Register of Controlled Trials were searched from inception through to December 2014 for RCTs that explored the efficacy and safety of landiolol on the prevention of AF after cardiac surgery. Pooled results were expressed as risk ratios (RRs) with 95% confidence intervals (CIs). Nine eligible RCTs involving 807 patients were included in this meta-analysis. Compared with the control group, landiolol was associated with a significant reduction of AF after cardiac surgery (RR=0.41; 95% CI 0.32-0.52; P<0.001), and the administration of landiolol seems more effective in patients who underwent coronary artery bypass grafting (CABG) (RR=0.36; 95% CI 0.25-0.52; P<0.001). Compared with placebo, no difference was detected in the incidence of major complications (RR=0.77; 95% CI 0.34-1.72; P=0.52). Landiolol is effective in prevention of AF after cardiac surgery and without increasing the risk of major complications. PMID- 26379819 TI - Clinicopathological and prognostic significance of MUC4 expression in cancers: evidence from meta-analysis. AB - Mucin4 (MUC4) is a secreted glycoprotein. Numerous studies had indicated that MUC4 was an attractive prognostic tumor biomarker. However, the results of different studies have been inconsistent. So we conducted this meta-analysis to explore the association between MUC4 expression and cancer prognosis. A systematically comprehensive search was performed through PubMed, EMBASE and CNKI (Chinese National Knowledge Infrastructure). Prognostic value of MUC4 expression in malignancy patients was evaluated by pooled hazard ratios (HRs) and their 95% confidence intervals (CIs). Meanwhile, pooled odds ratio (OR) with 95% CI was appropriate for the association between MUC4 expression and clinicopathological parameters. Eighteen studies including 1,933 patients were enrolled in this meta analysis. Significant association was found between elevated MUC4 expression and poorer overall survival (OS) with pooled hazard ratio (HR) of 1.87 [95% confidence interval (CI): 1.58-2.23, P<0.001]. Significant associations were also detected in biliary tract carcinoma (HR: 2.41, 95% CI: 1.69-3.42, P<0.001), pancreatic cancer (HR: 2.01, 95% CI: 1.42-2.86, P<0.001) and colorectal cancer (HR: 1.73, 95% CI: 1.17-2.54, P=0.006). Moreover, combined odds ratio (OR) of MUC4 indicated that MUC4 overexpression was associated with tumor stage, tumor invasion and lymph node metastasis. Our results demonstrated that MUC4 may be exploited as a novel prognostic biomarker for cancer patients. PMID- 26379821 TI - Autophagy knocked down by high-risk HPV infection and uterine cervical carcinogenesis. AB - Cervical cancer is a leading cause of cancer death among women in the world. The specific etiopathogenesis of cervical cancer is indeed complex. Even so, we should make arduous efforts to have a precise understanding of the complicate cellular/molecular mechanisms underlying initiation, progression and/or prevention of the cervical cancer. The high-risk human papillomavirus (hrHPV) is considered as the major causative agent of cervical cancer. But with the existence of hrHPV only is not sufficient, autophagy plays a vital character in the development of cervical cancer. Autophagy is the endogenous, tightly regulated cellular "housekeeping" process responsible for the degradation of damaged and dysfunctional cellular organelles and protein aggregates. Our aims in this review were (1) to provide a brief synopsis of process of autophagy (including an overview of the key molecular mediators of this catabolic process and its relationship with hrHPV infection) and (2) most importantly, summarize the current evidence for autophagy-mediated cervical carcinogenesis. One of the latest opinions about the etiopathogenesis is that hrHPV leads to the occurrence of cervical cancer via inhibiting the host's autophagy. The infection of hrHPV will cause the autophagy of cancerous cells, resulting in autophagic cell death, which will suppress the further infection of HPV in return. But the autophagy would be knocked down by the hrHPV, which means the protecting action would end with failure. What's worse, the negative denouement will enhance the infectivity of HPV ultimately, which leads to accelerate cervical carcinogenesis. PMID- 26379822 TI - Application of elderly donor for liver transplantation. AB - Recently, much more attention has been paid on application of elderly donor due to the shortage of organs. Although liver quality of elderly donors may be sub optimal comparing with that from younger donors, primary non-function of a liver graft is a rare event. On the other hand, long-term graft and recipient survival for usage of elderly grafts has become a major concern and focus of research. Many transplant centers have changed the upper limit of donor age from previous 50 to 70 or even 75-year-old and achieved good graft function. Although some scholars believed that liver transplant using elderly grafts was associated with high probability of delayed liver function recovery, graft loss and hepatitis C recurrence, reports from several transplant centers document that long-term survival of grafts and recipients may be significantly improved through certain screening of donors and recipients before transplant. In conclusion, it is very important and relatively safe to use grafts from elderly donors to expand the donor pool. However, elderly donors and corresponding recipients must be carefully selected before transplant. The long-term effect of advanced age on grafts and recipients need to be evaluated through a comprehensive and long-term in-depth observation. PMID- 26379823 TI - A comparison of surgical procedures and postoperative cares for minimally invasive laparoscopic gastrectomy and open gastrectomy in gastric cancer. AB - Minimally invasive, laparoscopic gastrectomy (LG) has assumed an ever-expanding role in gastric cancer treatment. Accumulating data so far seem to suggest that LG is at least a viable alternative of conventional open gastrectomy (OG) in different contexts. However, even though reviews and meta-analyses have compared the advantages and limitations of each option, it is still controversial whether LG is a better alternative to OG, especially in advanced gastric cancer (AGC). The major goal of this study is to evaluate the readouts of LG, in comparison with OG. A literature search was performed for studies published from 2009 to 2013. Medical records of 20868 gastric cancer patients from 32 independent studies were reviewed and analyzed. All 32 studies concluded that LG is at least comparable with OG. LG is superior to OG in offering less blood loss, shorter hospital stay, and lower risk of complications, although LG is probably inferior in operative time, and not different from OG in mortality. Considering the merits and the potential future technical improvement, it is reasonable to speculate that LG may eventually replace OG in most clinical contexts. PMID- 26379820 TI - Vitamin D and chronic hepatitis C: effects on success rate and prevention of side effects associated with pegylated interferon-alpha and ribavirin. AB - Chronic hepatitis C (CHC) is one of the most common causes of liver diseases worldwide, affecting 3% of the world population and 3 to 4 million people acquire new infection annually. Despite the recent introduction of novel antiviral drugs for the treatment of CHC, these drugs are expensive and the access to them is not an option for many patients. Hence, the traditional therapy by pegylated interferon-alpha (Peg-IFN-alpha) and ribavirin may still have a role in the clinical management of CHC especially in developing countries. However, this standard therapy is associated with several severe extra-hepatic side effects and the most common adverse events are hematological abnormalities and thyroid disorders and they could result in dose reduction and/or termination of therapy. Vitamin D has been shown to be a key regulatory element of the immune system, and its serum concentrations correlate with the severity of liver damage and the development of liver fibrosis/cirrhosis. Furthermore, supplementation with vitamin D with Peg-IFN-alpha based therapy for the treatment of CHC could be beneficial in increase the response rate to Peg-INF-alpha based therapy. Vitamin D has also been shown to regulate the thyroid functions and the process of erythropoiesis. This review appraises the data to date researching the role of vitamin D during the treatment of CHC and the potential role of vitamin D in preventing/treating Peg-IFN-alpha induced thyroiditis and anemia during the course of treatment. PMID- 26379824 TI - Progress of EGFR-TKI and ALK/ROS1 inhibitors in advanced non-small cell lung cancer. AB - To discuss the mechanism and clinical application of EGFR-TKI and ALK/ROS1 inhibitors in non-small cell lung cancer (NSCLC), we reviewed recent available data mainly from PubMed. We found that chemotherapy, progression-free survival (PFS), objective response rate (ORR), and quality of life of patients with advanced NSCLC can be greatly improved in these drugs medication compared with conventional chemotherapy. Though many questions like resistance to EGFR-TKI and ALK/ROS1 inhibitors exist, molecular targeted therapy is an important therapeutic method for the management of NSCLC. The role of molecule targeted therapy in the initiation and development of NSCLC deserves further study. PMID- 26379826 TI - Effect of L-arginine supplementation on insulin resistance and serum adiponectin concentration in rats with fat diet. AB - OBJECT: The purpose of this study was to determine whether supplementation with L arginine, a substrate used in the production of nitric oxide, had an effect on adiponectin concentration in rats fed a high-fat diet. The influence of L arginine on insulin resistance was also evaluated. MATERIALS AND METHODS: The experiment was performed using 36 Wistar rats divided into three groups: group 1 was fed a standard diet, group 2 a high-fat (HF) diet, group 3 a HF diet supplemented with L-arginine. After 42 days, serum levels of lipids, glucose, insulin, NO, and adiponectin were measured. Insulin resistance (IR) was estimated by the Homeostasis Model Assessment (HOMA). RESULTS: Body mass was equal in all 3 groups, at the beginning as well as at the end of the study, however, in group 2 the amount of visceral fat was greater after 42 days. In group 3, there was a tendency for visceral fat to decrease. An increase in cholesterol, triglycerides, insulin and HOMA-IR, as well as a decrease in NO and adiponectin were seen in group 2, while in group 3, L-arginine supplementation ameliorated these disturbances. CONCLUSIONS: Our study shows that L-arginine supplementation in rats fed a HF diet is associated with an increase in insulin sensitivity. Our findings suggest that the underlying mechanism could be at least partially related to an increase in adiponectin concentration. PMID- 26379827 TI - Effect of calcitonin pretreatment on naturally occurring intervertebral disc degeneration in guinea pig. AB - INTRODUCTION: Our previous study suggested protective effects of calcitonin (CT) on experimental osteoarthritis. The aim of the present study was to provide evidence of whether CT pretreatment could prevent naturally occurring intervertebral disc degeneration in guinea pigs. METHODS: Forty-two 3 months old female guinea pigs were randomly assigned into 2 groups as follows: Twenty-four were treated by normal saline as control group and sacrificed at 3, 6, 9 and 12 months of age (6 animals at each time point), the other 18 were received salmon CT (8 ug/kg/day, everyday) treatment at 3 months of age and sacrificed at the age of 6, 9 and 12 months respectively. Van Gieson stain and the histological score were used to identify the histological changes of the lumbar intervertebral discs. The disc height and vertebral body height were measured. Immunohistochemistry measurements for glycosaminoglycan, type II collagen, and matrix metalloprotease (MMP)-1 expressions were performed. Bone quality and microstructural changes in the L3-6 lumbar vertebral bodies were assessed by bone mineral density (BMD), micro-CT analysis and biomechanical testing. RESULTS: Histological analysis indicated significantly higher disc degeneration scores in 9-month-old guinea pigs in comparison with younger animals, and grew higher with increasing age. CT treatment significantly reduced the histological score, and increased the disc height and the ratio to vertebral body height in 12 months old animals, as well as upregulated the glycosaminoglycan, type II collagen and inhibited the MMP-1 expression. Micro-CT analysis showed decreased percent bone volume (BV/TV) and increased trabecular separation (Tb.Sp), structural model index (SMI) in 12 months old animals in comparison with the younger animals. Markedly increased BV/TV and decreased Tb.Sp were observed in CT treated animals when compared with control animals. The biomechanical properties including maximum load, maximum stress, yield stress and elastic modulus increased from 3 to 6 months old and thereafter maintained in a stable level, which were enhanced by CT treatment. CONCLUSION: Pretreatment with CT could prevent naturally occurring intervertebral disc degeneration in guinea pigs, which might be related to the modulation of extracellular matrix metabolism and the integrity and biomechanical properties in adjacent vertebral body. PMID- 26379825 TI - Biomarkers of head and neck cancer, tools or a gordian knot? AB - Head and neck tumors comprise a wide spectrum of heterogeneous neoplasms for which biomarkers are needed to aid in earlier diagnosis, risk assessment and therapy response. Personalized medicine based on predictive markers linked to drug response, it is hoped, will lead to improvements in outcomes and avoidance of unnecessary treatment in carcinoma of the head and neck. Because of the heterogeneity of head and neck tumors, the integration of multiple selected markers in association with the histopathologic features is advocated for risk assessment. Validation of each biomarker in the context of clinical trials will be required before a specific marker can be incorporated into daily practice. Furthermore, we will give evidence that some proteins implicated in cell-cell interaction, such as CD44 may be involved in the multiple mechanism of the development and progression of laryngeal lesions and may help to predict the risk of transformation of the benign or precancerous lesions to cancer. PMID- 26379828 TI - Role of ((E)-(E)-4-(4-hydroxy-3-methoxyphenyl)-2-oxobut-3-en-1-yl 3-(4-hydroxy-3 methoxyphenyl) acrylate in preservation of spatial cognitive functions of rats with chronic epilepsy. AB - The present study demonstrates the effect of ((E)-(E)-4-(4-hydroxy-3 methoxyphenyl)-2-oxobut-3-en-1-yl 3-(4-hydroxy-3-methoxyphenyl) acrylate (CA) on spatial cognitive functions of rats with lobal cerebrovascular hypoperfusion. The bilateral common carotid arteries occlusion (2VO) surgery was performed to prepare the cerebrovascular hypoperfusion rat model. The effect of CA on spatial cognitive function was analysed using Morris water maze (MWM) test prior to and after 2VO operation. Sixty rats were randomly assigned into two groups of 30 each; long-term memory (LTM) and short-term memory (STM) groups. Both the groups were further divided into 3 subgroups: control, untreated and CA treated groups. The animals received 50 MUg/kg of CA for 10 weeks of 2VO operation following which all the subgroups were tested with MWM. Both the escape latency time and total distance travelled were significantly lower for control and CA treated groups compared to untreated group revealed by working memory test. The maze test performance for control and CA treated groups was found to be improved markedly. Similarly, the results from probe memory test performance revealed significant improvement for CA treated groups compared to untreated group. Therefore, CA exhibits significant effect on the spatial cognitive preservation in rats with chronic epilepsy. PMID- 26379829 TI - Transarterial chemoembolization (TACE) plus percutaneous ethanol injection (PEI) for the treatment of unresectable hepatocellular carcinoma: a meta-analysis of randomized controlled trials. AB - Transarterial chemoembolization (TACE) plus percutaneous ethanol injection (PEI) have been used for patients with unresectable hepatocellular carcinoma (HCC). However, whether the combination therapy of TACE plus PEI is better than TACE or PEI alone in the treatment of HCC remains controversial. Thus, we conducted this meta-analysis to assess the efficacy of combined therapy for unresectable HCC compared with that of TACE or PEI alone. Randomized controlled trials (RCTs) published from Pubmed, Embase, Web Of Science, Chinese Biomedical Literature database (SinoMed), China National Knowledge Infrastructure (CNKI), and Wanfang database, were systematically reviewed to assess the survival benefits and tumor recurrence for HCC patients treated with TACE plus PEI. Pooled risk ratio (RR) with 95% confidence intervals (95% CIs) for survival rate and tumor recurrence rate were calculated using a random-effects or fixed-effects model, depending on the heterogeneity between the included studies. 19 RCTs met the inclusion criteria were included in this meta-analysis with a total number of 1948 patients. The pooled results showed that the combination therapy of TACE plus PEI significantly improved 1, 2, 3-year survival rate [RR1-year = 1.24, 95% CI: 1.17 1.31, P = 0.000; RR2-year = 1.64, 95% CI: 1.44-1.87, P = 0.000; RR3-year = 2.27, 95% CI: 1.93-2.67, P = 0.000] compared with that of TACE or PEI alone. The local tumor recurrence rate in HCC patients treated with TACE plus PEI was lower than that of monotherapy (RR = 0.53, 95% CI: 0.29-0.96; P = 0.035). The combined therapy of TACE with PEI also significantly reduced the AFP level (RR = 1.40, 95% CI: 1.19-1.66, P = 0.000) and tumor size (>50%) (RR = 1.61, 95% CI: 1.40-1.85, P = 0.000). This meta-analysis confirms the benefits of TACE + PEI in the treatment of unresectable HCC, with an improvement in survival rate, and a reduction in local tumor recurrence, AFP level, and tumor size. PMID- 26379830 TI - Gene function analysis in osteosarcoma based on microarray gene expression profiling. AB - Osteosa rcoma is an aggressive malignant neoplasm that exhibits osteoblastic differentiation and produces malignant osteoid. The aim of this study was to find feature genes associated with osteosarcoma and correlative gene functions which can distinguish cancer tissues from non-tumor tissues. Gene expression profile GSE14359 was downloaded from Gene Expression Omnibus (GEO) database, including 10 osteosarcoma samples and 2 normal samples. The differentially expressed genes (DEGs) between osteosarcoma and normal specimens were identified using limma package of R. DAVID was applied to mine osteosarcoma associated genes and analyze the GO enrichment on gene functions and KEGG pathways. Then, corresponding protein-protein interaction (PPI) network of DEGs was constructed based on the data collected from STRING datasets. Principal component of top10 DEGs and PPI network of top 20 DEGs were further analyzed. Finally, transcription factors were predicted by uploading the two groups of DEGs to TfactS database. A total of 437 genes, including 114 up-regulated genes and 323 down-regulated genes, were filtered as DEGs, of which 46 were associated with osteosarcoma by Disease Module. GO and KEGG pathway enrichment analysis showed that genes mainly affected the process of immune response and the development of skeletal and vascular system. The PPI network analysis elucidated that hemoglobin and histocompatibility proteins and enzymes, which were associated with immune response, were closely associated with osteosarcoma. Transcription factors MYC and SP1 were predicted to be significantly related to osteosarcoma. The discovery of gene functions and transcription factors has the potential to use in clinic for diagnosis of osteosarcoma in future. In addition, it will pave the way to studying mechanism and effective therapies for osteosarcoma. PMID- 26379831 TI - Effects of sericin on the testicular growth hormone/insulin-like growth factor-1 axis in a rat model of type 2 diabetes. AB - This study investigated the effects of sericin on the testicular growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis in rats with type 2 diabetes mellitus. Forty rats were randomly assigned to normal control, type 2 diabetes mellitus, sericin and metformin treated groups. Type 2 diabetes was established by repeated intraperitoneal injection of streptozotocin, and identified by blood glucose >=16.7 mmol/L at 1 week. The diabetic rats were given no other treatment, these rats in the sericin group were intragastrically perfused with 2.4 g/kg sericin and the metformin treated rats were intragastrically perfused with 55.33 mg/kg Metformin daily for 35 consecutive days. Enzyme-linked immunosorbent assays were used to determine serum testosterone, growth hormone and IGF-1 levels. Immunohistochemical staining, western blotting and reverse transcription-PCR were used to determine testicular growth hormone, growth hormone receptor and IGF-1 expression. The sericin significantly reduced serum growth hormone levels, downregulated growth hormone expression, increased serum testosterone and IGF-1 levels, and upregulated testicular growth hormone receptor and IGF-1 expression. Moreover, there were no significant differences in any of the parameters between the sericin and metformin treated groups. These findings indicated that sericin improved spermatogenic function through regulating the growth hormone/IGF-1 axis, thereby protecting reproductive function against diabetes-induced damage. PMID- 26379832 TI - Resveratrol attenuates inflammation and oxidative stress induced by myocardial ischemia-reperfusion injury: role of Nrf2/ARE pathway. AB - The protective role of resveratrol in myocardial ischemia/reperfusion is not well understood. The aim of this study was to investigate whether resveratrol modulates inflammation and oxidative stress and the possible role of nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway in an ischemia/reperfusion injured rat heart model. Rats were randomly exposed to sham operation, myocardial ischemia/reperfusion (MI/R) alone, and MI/R + resveratrol. The results demonstrated that compared to MI/R, resveratrol improved cardiac function, reduced myocardial infarction area, myocardial myeloperoxidase (MPO) levels, serum creatinine kinase (CK) and lactate dehydrogenase (LDH) levels. Resveratrol also markedly enhanced the activities of antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH PX), and reduced the level of malondialdehyde (MDA) in MI/R rats. Resveratrol also enhanced levels of Nrf2 and heme oxygenase-1. In summary, these results demonstrated that resveratrol exerted significant antioxidant and cardioprotective effects following myocardial ischemia, possibly through the activation of the Nrf2/ARE signaling pathway. PMID- 26379833 TI - XRCC1 Arg399Gln polymorphism is not associated with breast cancer in Chinese. AB - BACKGROUND: A number of studies have been conducted to explore the association of XRCC1 polymorphisms with Breast cancer (BC) risk in Asians, but the results have been inconsistent. We therefore performed the present meta-analysis to explore the relationship in detail. MATERIALS AND METHODS: Reported studies were searched from 1990 to October 15, 2014 in PubMed and Wan fang Med Online. We performed a meta-analysis of 13 published case-control studies fitting our eligibility criteria. These studies involved XRCC1 Arg399Gln polymorphisms in 4984 BC cases and 5744 controls in dominant (ArgArg vs. GlnGln+ArgGln), recessive (ArgGln+ArgArg vs. GlnGln), and co-dominant (ArgArg vs. GlnGln) inheritance models. The total odds Ratio (OR) and 95% CI were calculated and analyzed by Review Manager 5.2 and STATE 12. RESULTS: Overall, significantly increased BC risk was observed in any genetic model (dominant model: odds ration [OR] = 1.31, 95% confidence interval [CI] = [1.08, 1.58]; recessive model: OR = 0.63, 95% CI = [0.50, 0.81]; codominant model: OR = 2.52, 95% CI: [1.38, 4.60]) when all eligible studies were pooled into the meta-analysis. In further stratified analyses, no association was found between Arg399Gln polymorphism and BC risk in Chinese fewer than three hereditary models. CONCLUSIONS: Our results suggest that the XRCC1 Arg399Gln polymorphism may be associated with increased Breast cancer risk among Asians, except Chinese population. PMID- 26379834 TI - Co-culture of neuroepithelial stem cells with interstitial cells of Cajal results in neuron differentiation. AB - OBJECTIVE: The interstitial cells of Cajal (ICCs) interact morphologically and functionally with the elements of the enteric nervous system in the digestive tract. However, direct evidence that ICCs participate in the differentiation of the enteric nervous system is lacking. In this work, we examined in co-culture experiments whether ICCs could stimulate the differentiation of neuroepithelial stem cells (NESCs) to neurons. METHODS: NESCs were harvested from the neural tube of embryonic (E11.5) rats, and ICCs were isolated from the colons of newborn rats. Various cell types were identified immunohistochemically. RESULTS: NESCs reacted with antibodies to the stem-cell marker nest in; ICCs reacted with c-kit antibodies. NESCs, when differentiated into astrocytes, were identified with a marker GFAP, and neurons with marker MAP2. NESCs co-cultured with ICCs, compared with NESCs cultured alone, yielded a significantly greater number of cells positive for the neuronal markers PGP9.5 and nNOS. The co-cultured NESCs also produced more PGP9.5 and nNOS proteins, as measured by Western blotting. In addition, co-cultured ICCs connected morphologically with differentiated NESCs. CONCLUSION: These in vitro findings demonstrated that ICCs could induce the neuronal differentiation of NESCs, which connected with differentiated neurons into a network morphologically. The findings provide an experimental basis for in vivo application of the simultaneous transplantation of NESCs and ICCs. PMID- 26379836 TI - Homeobox B7 promotes the osteogenic differentiation potential of mesenchymal stem cells by activating RUNX2 and transcript of BSP. AB - Mesenchymal stem cells (MSCs) are a reliable cell source for tissue regeneration. However, the molecular mechanisms underlying the directed differentiation of MSCs remain unclear; thus, their use is limited. Here, we investigate HOXB7 function in the osteogenic differentiation potentials of MSCs using stem cells from apical papilla (SCAPs) and bone marrow stem cells (BMSCs). The HOXB7 gene is highly expressed in BMSCs compared with dental tissue-derived MSCs. We found that, in vitro, over-expression of HOXB7 in SCAPs enhanced alkaline phosphatase (ALP) activity and mineralization. HOXB7 over-expression affected the mRNA expression of osteonectin (ON), collagen alpha-2(I) chain (COL1A2), bone sialoprotein (BSP), and osteocalcin (OCN), led to the expression of the key transcription factor, runt-related transcription factor 2 (RUNX2), and promoted SCAP osteogenic differentiation in vitro. The knock-down of HOXB7 inhibited ALP activity, mineralization, and the expression of ON, BSP, COL1A2, OCN, and RUNX2 in BMSCs in vitro. In addition, transplant experiments in nude mice confirmed that SCAP osteogenesis was triggered when HOXB7 was activated. Furthermore, Over-expression of HOXB7 significantly increased the levels of HOXB7 associated with the BSP promoter by ChIP assays. Taken together, these results indicate that HOXB7 enhances SCAP osteogenic differentiation by up-regulating RUNX2 and directly activating transcript of BSP. Thus, the activation of HOXB7 signaling might improve tissue regeneration mediated by MSCs. These results provide insight into the mechanism underlying the directed differentiation of MSCs. PMID- 26379835 TI - Neuroprotective properties of vitamin C on equipotent anesthetic concentrations of desflurane, isoflurane, or sevoflurane in high fat diet fed neonatal mice. AB - Obesity has been reported to be one of the significant contributors to various chronic disease conditions. Childhood obesity has been on an alarming increase over recent years leading to various health complications. Millions of children undergo surgery each year as a part of medical care on various health grounds. In the present study, influence of vitamin C on the effect of obesity and over weight under anaesthetic exposure was analysed. Separate groups of neonatal mice (C57BL/6) were fed on high-fat diet to induce obesity. The mice were administered with vitamin C at 30 and 60 mg/kg b.wt post natal day 1 (P1) to P21. P7 mice were exposed to equipotent doses of isoflurane or sevoflurane or desflurane. Neuroapoptosis was assessed by measuring activated caspase-3 and TUNEL assay. Plasma S100beta levels were detected by ELISA. The mice were assessed for their general behaviour. Morris water maze test was performed to assess the spatial working memory. Anesthesia exposure caused severe neuroapoptosis and also raised the levels of plasma S100beta. Neuroapotosis, working memory and learning impairments observed following anesthetics were comparatively more profound on high fat diet fed mice. Desflurane exposure resulted in higher apoptotic counts, learning and memory deficits than equipotent dose of isoflurane and sevoflurane. Vitamin C supplementation offered significant protection against anesthetic induced neurotoxicity and behavioural alterations. Vitamin C administration resulted in marked reduction in neurotoxicity induced by anesthesia and as well improved learning and memory of both normal and high fat diet fed mice. PMID- 26379837 TI - Folic acid in combination with adult neural stem cells for the treatment of spinal cord injury in rats. AB - PURPOSE: To observe the therapeutic effect of folic acid in combination with adult neural stem cells on spinal cord injury and to investigate the possible mechanism. METHODS: A total of 120 Wistar rats were randomly assigned to six groups: normal, model, sham-surgery, folic acid injection, adult neural stem cell transplantation, and combination (folic acid injection + adult neural stem cells transplantation) groups. Morphology of neural stem cells was observed by inverted microscopy. Expression of CD105, CD45, CD44, and CD29 were detected by flow cytometry; expression of neuron-specific enolase and glial fibrillary acidic protein were determined by immunofluorescence. Motor coordination and integration capabilities were assessed using BBB scores; Morphology of spinal cord tissues was observed by hematoxylin-eosin staining and 5-bromodeoxyuridine immunohistochemistry. GDNF, BDNF and NT-3 expression in spinal cord tissues were determined by ELISA; while expression of the apoptosis-related proteins BCL-2, Bax and caspase-3 was detected using western blotting. RESULTS: Flow cytometry showed that the isolated cells were positive for CD44 and CD29 and negative for CD105 and CD45. Combination treatment significantly improved the behavior of model rats with spinal cord injury, attenuated inflammatory reaction of spinal cord tissues, restored injured nerve cells, and increased expression of GDNF, BDNF and NT-3 in spinal cord tissues, up regulated BCL-2 expression, and down regulated Bax and caspase-3 expression. CONCLUSIONS: Folic acid in combination with adult neural stem cells significantly improved nerve function and plays a key role in maintaining microenvironment homeostasis in the neurons of rats with spinal cord injury. PMID- 26379838 TI - Silencing of DUSP6 gene by RNAi-mediation inhibits proliferation and growth in MDA-MB-231 breast cancer cells: an in vitro study. AB - BACKGROUND: Dual-specificity phosphatase 6 (DUSP6) is a negative feedback mechanism of the mitogen-activated protein (MAP) kinase superfamily (MAPK/ERK, SAPK/JNK, p38), that is associated with cellular proliferation and differentiation. It has been reported that the expression of DUSP6 in different types of breast cancer is diverse and therefore it has altered functions in various types of breast cancer. Our aim was to explore the exact function of DUSP6 in triple-negative breast cancer cells (MDA-MB-231 cell) and to determine whether the suppression of DUSP6 by small interfering RNA (siRNA) and mircroRNA (miRNA) inhibits the growth of human MDA-MB-231 breast cancer cells. METHODS: DUSP6-siRNA was used to inhibit the expression of DUSP6 directly and miR-145 to inhibit the expression of DUSP6 either in MDA-MB-231 breast cancer cells and successful transfection being confirmed by Real-time PCR and Western Blotting. Down regulation of DUSP6 in MDA-MB-231 cells suppressed the cell proliferation as investigated by MTT assay and colony form assay. Transwell test and Scratch assay were conducted to investigate the migration and invasion of MDA-MB-231 cells. T test (two-tailed) was used to compare differences between groups, and the significance level was set at P<0.05. RESULTS: DUSP6 mRNA expression and protein expression were reduced after transfection with DUSP6-siRNA directly and similar trend with transfection with miR-145. The treated group with DUSP6-siRNA or miR 145 suppressed MDA-MB-231 cells proliferation, migration and invasion, and meanwhile the cells were arrested at G0/G1 phase. CONCLUSIONS: DUSP6 plays a role in triple-negative breast cancer cells that might promote growth in MDA-MB-231 triple-negative breast cancer cells. PMID- 26379839 TI - Protective effect of resveratrol against methotrexate-induced oxidative stress in the small intestinal tissues of rats. AB - The effect of resveratrol on the damage induced by methotrexate (MTX) in rat duodenum and jejunum tissue was investigated and evaluated in comparison with famotidine. The rats were divided into four groups as healthy group (HG), resveratrol+MTX (RMTX) group, famotidine+MTX (FMTX) group and the control group which received MTX (MTXC). RMTX group was given resveratrol 25 mg/kg and FMTX group famotidin 25 mg/kg, while MTXC and HG groups were orally administered distilled water once a day for 30 days. The rats in RMTX, FMTX and MTXC groups were given MTX of 5 mg/kg dose by the same way for 30 days. At the end of this period, amount of MDA, 8-OH/Gua and tGSH, and MPO gene expression were measured in the duodenal and jejunal tissues and the results were histopathologically evaluated. Resveratrol and famotidine were found to significantly prevent elevation of the MDA, 8-OH/Gua and MPO parameters with MTX and decrease of the levels of tGSH in the duodenal and jejunal tissues. Both drugs prevented severe damage to the villus and crypt epithelium in the duodenum and jejunum, congestion and hemorrhage, inflammatory cell infiltration and necrosis in the mucosa and submucosa due to MTX administration. Resveratrol could be considered in the clinical practice for treatment of the tissue damage in the intestines due to use of MTX, in comparison with famotidine. Resveratrol may be more advantageous than famotidine in long-term use against MTX toxicity since it does not inhibit gastric acid secretion. PMID- 26379840 TI - Promising potency of retinoic acid-poly(ethylene glycol)-thiol gold nanoparticle conjugates for cervical cancer treatment. AB - We investigated the effect of synthesized retinoic acid-poly(ethylene glycol) thiol gold nanoparticle conjugates on cervical carcinoma cells. Cervical cancer is the major cause of deaths for the women of reproductive age in the developing countries. Compared to retinoic acid, the nanoparticle conjugates exhibited better activity against cervical carcinoma. Selective delivery of gold nanoparticle conjugates to estrogen receptor positive cervical cancer cells with 6-fold enhanced drug potency was observed. Transfer of gold nanoparticles was found to be dominated by estrogen ligand and receptor. It appeared that retinoic acid nanoparticle conjugates were selectively taken and retained by the estrogen receptor alpha present in the plasma membrane. Thus IC50 values for RA-PEG-SH were significantly improvedon nanoparticle ligation. Cells on treatment with RA PEG-SH-AuNPsshowed growth inhibition at 12 and 24 h after incubation. The IC50 for RA in RA-PEG-SH-AuNPs after 12 and 24 h were 3 and 1 MUM, respectively. Thus, the use of RA nanoparticle conjugates can be a better strategy for cervical carcinoma treatment. PMID- 26379841 TI - Interaction between carbenoxolone and valproic acid on pentylenetetrazole kindling model of epilepsy. AB - Gap junctions play an important role in the synchronized neuronal discharges. The main reason of the epileptic seizures is disruption of this synchronization. Therefore, the aim of the present study is to explore the combination valproic acid with carbenoxolone in pentylenetetrazole-kindled rats. In the first set of experiments, pentylenetetrazole (35 mg/kg intraperitoneally was administered to the rats to produce the kindling and then permanent screw electrodes to record electroencephalographic signals. The kindled rats were divided into six groups. While electroencephalographic recordings received from animals, behavioral evaluation was done by an observer. The data analysis was performed using T test and Mann-Whitney U tests. The dose of 40 mg/kg carbenoxolone was the most effective in carbenoxolone treatment groups. It prevented generalized seizures by 50%, reduced seizure stage, seizure duration and spike frequency. There was no significant difference between carbenoxolone-valproic acid combination and valproic acid on any seizure parameters. The current study is the first study which shows the interaction of carbenoxolone with valproic acid in pentylenetetrazole kindling model. As a result, carbenoxolone-valproic acid combination was not more effective than the standalone use of these drugs. PMID- 26379842 TI - Prognostic significance of interleukin-17 in solid tumors: a meta-analysis. AB - BACKGROUND: The prognostic significance of intratumoral and peripheral interleukin-17 (IL-17) in tumors has been studied worldwide during these years, providing un-uniformed conclusions. METHODS: We conducted a meta-analysis of published literatures that evaluated the correlation between IL-17 and clinical staging, overall survival (OS) and/or disease free survival (DFS). RESULTS: A total of 28 studies enrolling 2902 patients were included. For the overall population, a high expression of IL-17 was found significantly correlated with worse DFS (HR = 1.59, 95% CI: 1.24-2.03) in patients with solid tumors. For gastrointestinal tumors, patients with IL-17 high seemed to have worse OS (HR = 1.85, 95% CI: 1.24-2.75) and DFS (HR = 2.41, 95% CI: 1.98-2.92). Sub-group meta analysis revealed that IL-17 indicated late clinical staging in non-small cell lung cancer (NSCLC) patients (HR = 2.33, 95% CI: 1.25-4.32), on the other hand, early clinical staging in patients with esophageal squamous carcinoma (HR = 0.63, 95% CI: 0.42-0.94). Negative impacts of IL-17 on OS were shown in patients with hepatocellular carcinoma (HCC) (HR = 1.87, 95% CI: 1.23-2.84) or NSCLC (HR = 1.55, 95% CI: 1.02-2.35). However, positive impacts on OS were provided in patients with esophageal squamous carcinoma (HR = 0.65, 95% CI: 0.50-0.84). Besides, a high expression of IL-17 predicted better DFS in ovarian cancer patients (HR = 0.33, 95% CI: 0.11-1.00). CONCLUSIONS: Our meta-analysis revealed that IL-17 might correlate with poor OS and DFS in gastrointestinal tumors. Specifically, IL-17 was a detrimental factor for HCC and NSCLC patients, whereas a beneficial factor for patients with esophageal squamous carcinoma and ovarian cancer. PMID- 26379843 TI - Gender disparity in the role of TLR2 in post-ischemic myocardial inflammation and injury. AB - It is unclear whether Toll-like receptor (TLR) 2 plays a role in post-ischemic myocardial inflammatory response and cardiac dysfunction in both males and females. Permanent ischemia was induced in male and female C57BL/6J (wild-type, WT) and TLR2 knockout (KO) mice. Infarct size and left ventricular (LV) function were analyzed at day 7. Myocardial levels of monocyte chemoattractant protein-1 (MCP-1) and intercellular adhesion molecule-1 (ICAM-1), as well as neutrophil infiltration, were assessed at day 3, and mononuclear cell accumulation was determined at day 7. Lower MCP-1 and ICAM-1 levels, and reduced leukocyte accumulation correlated with smaller infarct size and improved LV function in male TLR2 KO mice. Female WT mice exhibited attenuated myocardial inflammatory response and injury, and TLR2 KO in females did not provide a protective effect although myocardial TLR2 levels in female WT mice were unaltered, and their cardiac cells responded to bacterial TLR2 agonist properly. TLR2 KO in male mice reduced post-ischemic myocardial inflammatory response, resulting in smaller infarct sizes and improved cardiac function. However, TLR2 KO was not beneficial in female mice. The gender disparity in the role of TLR2 in post-ischemic myocardial inflammatory response and myocardial injury suggests that interception with TLR2 signaling may have therapeutic potentials only in males. PMID- 26379844 TI - APOBEC3A possesses anticancer and antiviral effects by differential inhibition of HPV E6 and E7 expression on cervical cancer. AB - Cervical cancer is the second most common cancer among women worldwide and is the leading cause of deaths in developing countries. Persistent infections with a subset of HPVs, called "high-risk HPVs", including HPV16 and HPV18, are the primary cause of cervical cancer. The apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC) family of proteins is a group of cellular enzymes that catalyze the deamination of cytidine (C) to uracil (U) in single stranded DNA/RNA, and functions as antiviral factors in the innate immune system of the host. Recent studies have shown that APOBEC3A could restrict certain DNA viruses, including HPVs. In this study, we confirmed that the expression of APOBEC3A was decreased in cervical cancer tissues. Furthermore, APOBEC3A inhibited the cervical cells proliferation, migration as well as invasion, and promoted apoptosis depend on cytidine deaminase. In addition, APOBEC3A decreased HPV16-E6, HPV16-E7 and HPV18-E6 depend on cytidine deaminase, but no effect on HPV18-E7. Therefore, we believe that, in cervical cancer cells, the expression of APOBEC3A possesses anticancer and antiviral effects by differential inhibition of HPV E6 and E7 expression depend on cytidine deaminase. PMID- 26379845 TI - Application of chrysophanol in zebrafish to reduce dietary introduced lipid and its possible mechanism. AB - PURPOSE: To explore the therapeutic potential and mechanism of chrysophanol on lipid-lowering function. METHODS: Zebrafish or larvae were employed to evaluate the effect of chrysophanol on lipid-lowering. Zebrafish of 5 day post fertilization (dpf, larva) and 13-week old were fed with high-cholesterol diet or high-fat to investigate the influence of chrysophanol comparing with atorvastain and co-administration of chrysophanol and atorvastain on subsistent blood lipid using the fluorescence microscope and lipid panel screen. Thereafter, we enrolled zebrafish of 7 dpf fed with high-fat diet to explore the lipid-lowering mechanism of chrysophanol basing on the frequency of peristalsis and the residual on the digestive wall. RESULTS: Chrysophanol could significantly lower cholesterol both in zebrafish and larvae (P < 0.05), and the co-administration of chrysophanol and atorvastatin had the best performance in reducing cholesterol (P < 0.05). Chrysophanol and atorvastain could also significantly lower triglyceride. Moreover, we found that chrysophanol attached on the digestive wall for a long time and enhanced the frequency of peristalsis. CONCLUSIONS: Chrysophanol has lipid-lowering effect both in zebrafish and larvae which may be attributed to the effect on the frequency of peristalsis and fat absorption, and co-administration with atorvastain performs better lipid-lowering effect in zebrafish. PMID- 26379846 TI - Effects of repeated high dosage of chloral hydrate and pentobarbital sodium anesthesia on hepatocellular system in rats. AB - This study aims to investigate the possible effects of repeated high dosage of chloral hydrate and pentobarbital sodium anesthesia on hepatocellular system in rats. Thirty Sprague Dawley rats were randomly divided into 3 groups: control group (group A), chloral hydrate group (group B) and pentobarbital sodium group (group C). Antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione s transferase (GST) and catalase (CAT) activities and thiobarbituric acid-reactive substances (TBARS) level as well as serum biochemical parameters alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and total bilirubin (T-BIL) were determined. Liver histopathological examinations were performed at termination. Furthermore, Bax and Bcl-2 expression, and caspase-3 activity were also evaluated. The SOD, GSH-Px, GST and CAT activities significantly decreased but TBARS levels increased in group B and C compared with group A. Hepatic injury was evidenced by a significant increase in serum ALT, AST and ALP activities in group B and C, which also confirmed by the histopathological alterations. Moreover, administration of chloral hydrate and pentobarbital sodium could induce certain hepatic apoptosis accompanied by the upregulated Bax expression, the downregulated Bcl-2 expression and Bcl-2/Bax ratio, and the increase of caspase-3 activity. Repeated high dosage of chloral hydrate and pentobarbital sodium anesthesia could produce hepatotoxicity. PMID- 26379847 TI - Clinical significance of incidental FDG uptake in the prostate gland detected by PET/CT. AB - The value of FDG-positron emission tomography/computed tomography (PET/CT) for detecting prostate cancer is unknown. We aimed to investigate the clinical value of incidental prostate FDG uptake on PET/CT scans. We reviewed 6128 male patients who underwent FDG-PET/CT scans and selected cases that reported hypermetabolic lesion in the prostate. The patients who have prior history of prostate carcinoma or prostate surgery were excluded from the study. We have analyzed the correlation between PET/CT findings and serum prostate-specific antigen (PSA) levels, imaging (USG), urological examinations and biopsy. Incidental 18F-FDG uptake of the prostate gland was observed in 79 patients (1.3%). While sixteen of them were excluded due to inadequate clinical data, the remaining 63 patients were included for further analysis. The patients were divided into two groups; 8 patients (12.7%) in the malignant group and 55 patients (87.3%) in the benign group. The SUVmax values were not significantly different between the two groups. In 6 (75%) patients with prostate cancer, FDG uptake was observed focally in the peripheral zone of the prostate glands. There was no significant correlation between the SUVmax and the PSA levels. Incidental 18F-FDG uptake in the prostate gland is a rare condition, but a substantial portion of it is associated with the cancer. Benign and malignant lesions of the prostate gland in FDG-PET/CT imaging could not be reliably distinguished. The peripheral focally FDG uptake of prostate glands should be further examined with the clinical and labaratory evaluations. PMID- 26379848 TI - Comparision of ultrasound-based methods of jugular vein and inferior vena cava for estimating central venous pressure. AB - OBJECTIVE: The aim in this study was to compare the ultrasound estimation of the jugular vein diameter (IJVmax, IJVmin) and area (IJVarea), the height of the right internal jugular vein (CVPusg), the vena cava diameter (IVCmax, IVCmin), and the vena cava index (IVCindex) with direct estimation of central venous pressure (CVPinv). METHODS: Ultrasonography was performed on 37 nonventilated and 36 ventilated patients while monitoring central venous pressure. The IJV and IVC were measured during the respiratory cycle and the IJVarea and IVCindex were calculated. Tapering portion of the right IJV defined and height from this point to the sternal angle was used to estimate CVPusg. RESULTS: A CVP of 10 mmHg was chosen as a clinically significant cutoff for high CVP, and 6 mmHg was chosen for low CVP estimation. The CVPusg, IJVmax and IJVmin correlated moderately with CVPinv (R2 = 0.66, 0.53, and 0.54, respectively) whereas the IVCmax, IVCmin and IVCindex showed poor correlation (R2 = 0.29, 0.32 and 0.27, respectively). The CVPusg cutoff value of 7 predicted CVPinv > 10 mmHg with sensitivity of 90%, specific-ity of 67.3% and predicted CVPinv < 6 mmHg with sensitivity of 77%, specificity of 68%. IJVmax, IJVmin, IJVarea and IVCmax showed high sensitivity (90.32%, 83.87%, 90.32%, and 93.10%, respectively) for low CVP levels. The IVCindex has high sensitivity (95.2%) and poor specificity (42.9%) for high CVP levels. CONCLUSION: IVCindex and CVPusg has better diagnostic performance for estimating high CVP. IJVmax, IJV area, and IVCmax showed high sensitivity and NPV for low CVP levels. PMID- 26379849 TI - Angioplasty versus bypass surgery in patients with critical limb ischemia-a meta analysis. AB - Background-Critical limb ischemia (CLI) is one of the most severe peripheral artery diseases. Angioplasty and bypass surgery are two major approaches for the treatment of CLI, however, it remains unclear which treatment has better benefit/risk ratio. In this paper, we performed a meta-analysis on the available clinical trials to compare these two approaches in terms of mortality, amputation free survival, 5-year leg salvage, and freedom from surgical re-intervention. The results of this article will provide evidence based information for clinical treatment of CLI. Method-Randomized clinical trials comparing results between angioplasty and bypass surgery in CLI were identified by searching Pubmed (2000 2014) and EMBASE (2000-2014) using the search terms "angioplasty" or "bypass", "CLI" and "clinical trials". Primary outcome subjected to meta-analysis was amputation (of trial leg) free survival in 5 years. Secondary outcomes were 30 day mortality; mortality, re-interventions and leg salvage in 1, 3 and 5 years. Results-Seven clinical trials were selected for meta-analysis. No significant difference was found in the primary outcome-amputation free survival, between angioplasty and bypass surgery groups. The amputation free survival in 1, 3 and 5 years were 332/498 (66.7%), 169/346 (48.8%) and 21/60 (35%) in angioplasty group, versus 484/749 (64.6%), 250/494 (50.6%) and 46/132 (34.8%), in bypass group, respectively. The 30 days mortality rate was significantly higher in bypass treatment group [79/1304 (6.1%)] than in angioplasty group [30/918 (3.3%) [95% CI 0.55 [0.36, 0.86], P=0.008). However, there was no statistical significance in 1, 3 and 5 years mortality between these two groups. Two clinical trials showed that there was no difference in leg salvage between angioplasty and bypass surgery groups either. In addition, no difference was observed in re-vasculation between the two groups. Conclusion-Angioplasty is non-inferior to bypass surgery in regarding the amputation free survival, re-vasculation, leg amputation and overall mortality. However, angioplasty is safer, simple, and less invasive and less cost procedure. It should be considered as the first choice for feasible CLI patients. PMID- 26379850 TI - Diagnostic value of IMP3 in pancreatic cancer: a meta-analysis. AB - BACKGROUND AND OBJECTIVES: An increasing number of studies have examined the ability of IMP3 (insulin-like growth factor 2 messenger RNA binding protein 3) to be a marker for the diagnosis of pancreatic cancer (PCa). The exact role of IMP3 needs to be elucidated. The aim of this study is to determine the overall accuracy of IMP3 in PCa through a meta-analysis of published studies. MATERIALS AND METHODS: Publications addressing the accuracy of IMP3 in the diagnosis of PCa were selected from Pubmed, Embase, Cochrane Library, Web of Science, and The Chinese Journals Full-text Database (CNKI). The following indexes of test accuracy were computed for each study: sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR). The diagnostic threshold identified for each study was used to plot a summary receiver operating characteristic (SROC) curve. Statistical analysis was performed by Meta-Disc 1.4 and STATA 12.0 software. RESULTS: 10 studies met the inclusion criteria. The summary estimates for IMP3 in the diagnosis of PCa were: sensitivity 0.82 (95% CI, 0.78-0.85), specificity 0.87 (95% CI, 0.83-0.90), positive likelihood ratio (PLR) 15.04 (95% CI, 1.83-123.26), negative likelihood ratio (NLR) 0.21 (95% CI, 0.10-0.46) and diagnostic odds ratio 70.10 (95% CI, 16.74-293.56). The SROC curve indicated that the maximum joint sensitivity and specificity (Q-value) was 0.87; the area under the curve was 0.94. CONCLUSION: Our findings suggest that IMP3 may be a useful diagnostic adjunctive tool for confirming PCa. However, further large scale studies are needed to confirm these findings. PMID- 26379851 TI - Polymorphisms in the nuclear excision repair gene ERCC2/XPD and susceptibility to cutaneous basal cell carcinoma. AB - Studies have investigated the relationship between XPD Lys751Gln and Asp312Asn genetic variants and risk of cutaneous basal cell carcinoma (BCC). However, the results remain inconclusive. We performed a meta-analysis, using a comprehensive strategy based on the allele model and a model-free approach, to investigate the association of between XPD Lys751Gln and Asp312Asn polymorphisms with BCC risk. For XPD Lys751Gln, no significant BCC risk was found in the allele model (OR = 0.97, 95% CI 0.90-1.04, I (2) = 35.3%, P heterogeneity = 0.125) and with model free approach (ORG = 0.95, 95% CI 0.87-1.04, I (2) = 15.9%, P heterogeneity = 0.296). For XPD Asp312Asn, there was also no association between this polymorphism and BCC risk in the allele model (OR = 0.94, 95% CI 0.86-1.03, I (2) = 0, P heterogeneity = 0.650) and with the model-free approach (ORG = 0.94, 95% CI 0.85-1.05, I (2) = 0, P heterogeneity = 0.603). Therefore, this meta-analysis suggests that the XPD Lys751Gln and Asp312Asn polymorphisms were not associated with BCC risk. Further large and well-designed studies are needed to confirm these findings. PMID- 26379852 TI - Experimental study of high-energy fractures delayed operation in promote bone healing. AB - To investigate role of delayed operation to stimulate growth of strong external callus in high-energy fractures, and explore a new way for bone healing. Twenty adult dogs were employed, and randomly divided into four groups, including group A-D. The dogs underwent osteotomy by wire saw in middle of femur, electric coagulation damaged surrounding periosteum, forming a 1 cm defect. Group A were internal fixed 14 days after osteotomy (higher-energy fractures delayed operation), Group B and C were internal fixed immediately (no delayed operation), Group D were internal fixed 14 days after osteotomy (delayed operation, but resected granulations around extremities). The results showed that groups of early fixed have no external callus growth and almost no growth in internal callus, these conditions leads to atrophy nonunion. On contrary, the porosis was strong and callus union was steady in group A and D, which have a delayed operation. In conclusion, early surgical fixation of high-energy fracture restrains external callus growth, easily lead to poor callus healing phenomenon of low-quality. Delayed surgical fixation can begin to repair soft tissues injury, stimulate external callus growth and improve fracture healing, so a small incision open reduction produce more robust growth effect than closed reduction. PMID- 26379853 TI - A meta-analysis of glutathione S-transferase M1 and T1 genetic polymorphism in relation to susceptibility to nasopharyngeal carcinoma. AB - OBJECTIVE: To investigate the relationship between glutathione S-transferase M1 (GSTM1), and T1 (GSTT1) genetic polymorphism and susceptibility to nasopharyngeal carcinoma (NPC) using meta-analysis method. METHODS: Data of published case control studies on the relationship between GSTT1, GSTM1 genetic polymorphism and susceptibility to NPC were collected from EMBASE, PubMed, Web of Science, China Academic Journals Full-text Database, Chinese Biomedical Literature Database, and Wanfang Database. Meta-analysis was conducted using Revman 5.2 software. RESULTS: Nine studies were included for meta-analysis with a total of 1295 cases of NPC patients and 1967 control individuals. Meta-analysis showed that the risk of NPC was significantly higher in population with GSTM1 gene deletion (OR=1.43, 95% CI: 1.42-1.65; P<0.001). Similarly, the risk of NPC was significantly higher in Chinese population with GSTM1 gene deletion (OR=1.38, 95% CI: 1.18-1.62; P<0.001). We did not find association between GSTT1 gene deletion and NPC risk not only in total population (OR=1.32, 95% CI: 0.92-1.87; P=0.12), but in Chinese population (OR=1.41, 95% CI: 0.97-2.04; P=0.07). CONCLUSION: GSTM1 genetic polymorphism, but GSTT1, is associated with susceptibility to NPC. PMID- 26379854 TI - Association between serum C-reactive protein value and prognosis of patients with non-small cell lung cancer: a meta-analysis. AB - OBJECTIVE: C-reactive protein (CRP) has been reported, with controversy, to be associated with poor survival of patients with non-small cell lung cancer (NSCLC). This meta-analysis aimed to evaluate the prognostic role of CRP in NSCLC. METHODS: We searched PubMed, EMBASE and CNKI databases for published studies that evaluated the prognostic role of CRP in NSCLC up to March 1, 2014. The data were analyzed using STATA software (Version 12.0; Stata Corporation). Hazard ratios (HRs) with a 95% CI and 5-year survival rates were calculated to evaluate the relationships between CRP levels and the prognosis of NSCLC patients. RESULTS: Eight studies were included, totaling 1668 NSCLC patients. The results revealed that elevated CRP values might predict poor 5-year overall survival rates (RR=2.15, 95% CI: 1.78-2.59) and poor 5-year disease-specific survival rates (RR=2.12, 95% CI: 1.56-2.88). The pooled HR between stage I/II and stage III/IV patients was 0.98 (95% CI: 0.26-3.63, P=0.976), which indicated that the difference between the survival rates of the patients with elevated CRP and those with undetectable CRP was not significant. In our survival analysis, the results of Egger's testing did not demonstrate evidence of publication bias (P=0.099). CONCLUSION: Elevated CRP level is relevant to poorer survival of NSCLC patients and might be used as a prognostic biomarker for NSCLC. PMID- 26379855 TI - IL-21 does not involve in OVA-induced airway remodeling and chronic airway inflammation. AB - Interleukin (IL-21) is a member of the type I cytokine family with sequence homology to IL-2, IL-4, and IL-15. IL-21 has been reported to improve symptoms of allergic rhinitis in mice. In this study we examined whether IL-21 signaling involved in allergic airway inflammation and remodeling in vivo by using ovalbumin (OVA)-induced chronic asthma model. We showed IL-21 level was increased in the serum of asthma models but not bronchoalveolar lavage fluid (BALF). Intranasal administration with recombinant mouse IL-21 or anti-IL-21 receptor (IL 21R) antibody did not affect OVA-induced chronic airway inflammation and airway remodeling in vivo and also not affect the expression of IL-13 and TGF-beta in BALF. Moreover, expression of IL-13 and TGF-beta was not affect by intranasal administration with recombinant mouse IL-21 or anti-IL-21R antibody. These results indicated that IL-21 signaling might not play an important role in airway inflammation and remodeling. PMID- 26379856 TI - Establishment of a new animal model for ischemic lumbar vertebrae. AB - Degeneration and ischemia of lumbar intervertebral disc has become a more and more important issue for elder people. However the mechanism for this is still known, largely due to a lack of a suitable animal model. In this study, we constructed a new animal model for the study of ischemic lumbar vertebrae. 42 New Zealand white rabbits were chosen for the study. For each rabbit, two vertebrae were used. L5 was set as the experimental group and L4 was set as the control group. Percutaneous lumbar puncture needles were applied in vertebrae adjacent to endplate for L5 and L4. For L4 1 ml saline was injected and for L5 1 ml pingyangmycin (2 mg/mL) was used. 1, 2, 3, 4, 5 weeks; 2 and 3 months after surgery, 6 rabbits at each time point were randomly chosen and underwent MRI, pathological test. The results in L5 and L4 were compared. Another 6 rabbits were used for DSA (Digital Subtraction Angiography) and vascular cast to study the length and diameters of the branches of lumbar artery. It was identified that since the third week, slightly hyperintense signal on T2-weighted image (T2WI) and fat-suppression T2-weighted image (FS T2WI) were detected. Lumbar vertebrae damage could be identified since the fourth week. Results of MRI and the size of pathological area were positively related (r=0.965, P<0.05). DSA and vascular cast could both clearly show the third level branches of lumbar artery. Our study suggested that injection of pingyangmycin via percutaneous lumbar needle could successfully induce ischemia in lumbar endplate. This method had little trauma, required a simple operation process and is highly repetitive. Besides, by vascular cast, the most important source of blood supply is the media branch of the lumbar artery. This branch could be a new therapy pathway for the degeneration of lumbar vertebrae. PMID- 26379857 TI - The Effect of NRAGE on cell cycle and apoptosis of human dental pulp cells and MDPC-23. AB - OBJECTIVES: Neurotrophin receptor-mediated melanoma antigen-encoding gene homology (NRAGE) is an important regulator of proliferation, cell cycle arrest and apoptosis. Our previous study showed that NRAGE is an important regulator of proliferation and odontogenic differentiation of mouse dental pulp cells. This study aimed to investigate the effects of NRAGE on the cell cycle and apoptosis on human dental pulp cells (hDPCs) and MDPC-23. MATERIALS AND METHODS: Cells were infected by recombinant lentivirus to stably knockdown the expression of NRAGE, then the biological effects of NRAGE on the MDPC-23 was detected. The cell cycle distributions and apoptosis of hDPCs and MCPC-23 were performed by flow cytometric analysis. Simultaneously, the cell cycle and apoptosis were also detected after cells treated with IKK inhibitor. RESULTS: The mRNA and protein levels of NRAGE decreased significantly after infected by recombinant lentivirus. Knockdown of NRAGE inhibited the apoptosis in hDPCs and MCPC-23. Knockdown of NRAGE show significantly G0G1 arrest in hDPCs, while no significantly difference in MDPC-23. Meanwhile, Knockdown of NRAGE activated the NF-kappaB signaling pathway. After treated with IKK inhibitor, the effect of NRAGE knockdown on apoptosis was reversed in both hDPCs and MDPC-23. CONCLUSION: NRAGE is a potent regulator for cell cycle and apoptosis of hDPCs. Knockdown of NRAGE inhibited apoptosis of hDPCs and MDPC-23 through the NF-kappaB signaling pathway. PMID- 26379858 TI - Turning left or right? A comparative analysis in adenocarcinomas of the esophagogastric junction according to the seventh AJCC TNM classification for cancers of the esophagus and stomach: experience in a Chinese single institution. AB - The seventh AJCC TNM classification defines rules for classifying adenocarcinomas of esophagogastric junction (AEG II and III) as a part of esophageal cancer. But there are still many controversies over the classification system. The study aims to evaluate and compare whether AEG should be classified as cancers of esophagus or stomach. A single-center cohort of patients with AEG or proximal third gastric adenocarcinoma underwent surgical resection with curative intent in Shanghai from November 2004 to July 2011. We compared the clinicopathologic features between AEG (n=291) and proximal third gastric adenocarcinoma (n=176) and analyzed overall survival probabilities of AEG using the latest seventh AJCC TNM classification for cancers. Patients with AEG not only show more advanced diseases, but also have a significantly worse 5-year survival rate than those with proximal third gastric adenocarcinoma (P=0.027). In 291 patients with AEG, the gastric T classification is monotone but indistinct except for pT2 versus pT3 (P=0.001) and pT4a versus pT4b (P=0.012). The esophageal T classification is neither monotone nor distinct. For the N classification, both schemes are monotone and distinct. The gastric scheme is indistinctive for stages IA versus IB (P=0.428), for IIA versus IIB (P=0.376), for IIB versus IIIA (P=0.086), for IIIA versus IIIB (P=0.087), and for IIIC versus IV (P=0.928). The esophageal scheme is indistinct only except for IIIB versus IIIC (P=0.002). The gastric scheme includes one heterogeneous stage group (stage IIIC, P<0.001), whereas all stage groups are homogeneous in the esophageal scheme. Although AEG shows different clinicopathological features and surgical outcomes of patients, the current seventh AJCC TNM classification which stages the AEG in the esophageal scheme does not demonstrate the advantages in the assessment of the patient prognosis. We propose a revised staging system to clarify the AEG with esophageal invasion. PMID- 26379859 TI - Polymorphisms in the GCKR are associated with serum lipid traits, the risk of coronary artery disease and ischemic stroke. AB - The present study was to determine the association of two single nucleotide polymorphisms (SNPs) in the glucokinase regulator gene (GCKR) and serum lipid levels, and the risk of coronary artery disease (CAD) and ischemic stroke (IS). Genotypes of the GCKR rs1260326 and rs8179206 in 1736 unrelated subjects (CAD, 584; IS, 555; and healthy controls; 597) were determined by the Snapshot technology platform. The genotypic and allelic frequencies of rs1260326 and rs8179206 were not different among the three groups (P > 0.05). The subjects with rs1260326TT genotype had higher serum low-density lipoprotein cholesterol (LDL-C) levels in controls, and higher triglyceride (TG) levels in CAD patients than the subjects with CC and CT genotypes after adjustment for age, sex, body mass index, blood pressure, alcohol consumption, and cigarette smoking (P < 0.05). The rs1260326TT genotype was also associated with decreased risk of IS in females (OR = 0.37, 95% CI: 0.18-0.76, P = 0.007). The present study shows that the GCKR rs1260326TT genotype is associated with high LDL-C in controls, high TG levels in CAD patients, and a decreased risk of IS in females. PMID- 26379860 TI - Design and finite element analysis of a novel sliding rod microscrew implantation device for mandibular prognathism. AB - Tooth distalization is an effective approach for mandibular prognathism. Current distalization devices are bulky and clinically complicated. Here, we designed a novel molar distalization device by using a sliding rod and a microscrew and performed a mechanical analysis and finite element model (FEM) analysis of force distribution and displacement of the upper canine, first and second premolar and first molar. A 2D FEM was constructed using the Beam3 element and a 3D FEM was constructed of the mandibular teeth, the periodontal membrane, and the alveolar bones using the UG software. The upper first molar was divided into 12 points on the dental surface to facilitate stress analysis. Force analysis using the ANSYS WORKBECNH revealed that, both horizontally and vertically, the traction force causing distalization of the first molar decreased when the spring coil moved down the L shaped sliding rod. The 3D FEM force analysis revealed distomedial displacement of the upper first molar when the sliding rod microscrew implantation device caused distalization of the molar. These findings support further exploration for the use of the sliding rod microscrew implants as an anchorage for group distal movement of the teeth of patients with mandibular prognathism. PMID- 26379861 TI - Long-term action of propofol on cognitive function and hippocampal neuroapoptosis in neonatal rats. AB - Propofol is a short-acting anesthetic and generally is utilized for the induction and maintenance of anesthesia in pediatrics and adults. However, whether repeated use of propofol affects long-term cognitive function remains unclear. This study investigated the effects of propofol on cognitive function and hippocampal neuroapoptosis in neonatal rat. A total of 112 male newborn 7-day old Sprague Dawley rats were randomly divided into 8 groups (n=14 rats per group) and intraperitoneally injected either with saline or propofol at 50, 100, and 150 mg/kg/day for 5 consecutive days. Four non-surgical groups were assigned as Con1, P50, P100, and P150. Four surgical groups were received an appendicectomy under propofol anesthesia and assigned as Con2, SP50, SP100, SP150. After 2 months raising, cognitive function, hippocampal neuroapoptosis, and intracephalic inflammatory cytokines were evaluated. There was no obvious effect on the cognitive function and neuroapoptosis after repeated use of propofol at a low dose for 5 days, whereas repeated use of propofol at a middle/high dose significantly increase the expression of apoptotic factors (caspase-3 and Bax), pro-inflammatory cytokines (IL-1beta, IL-6, and TNF-alpha), and impair the cognitive function. Thus, our data suggest that repeated use of propofol at a low dose may be safe during the period of brain growth spurt. Using propofol at a recommended or higher dose for anaesthesia may lead to the cognitive defects, attributed to hippocampal neuroapoptosis and the overexpression of pro inflammatory cytokines in the brain. PMID- 26379862 TI - Lenalidomide alone or in combination with chemotherapy treatment for subtypes of diffuse large B cell lymphoma: a systematic review and meta-analysis. AB - Lenalidomide has been shown to produce durable responses in patients with relapsed or refractory diffuse large B cell lymphoma (DLBCL). In order to gain better understanding of the efficacy of lenalidomide and compared the difference in clinical outcome between two subtypes of DLBCL. Seven eligible trials involving 375 adult patients were included in this meta-analysis. The patients in non-germinal center B-cell (non-GCB) subtype had higher overall response (OR) rate compared with GCB patients (P=0.21). In subgroup analysis, as first-line and second-line treatment for DLBCL patient, GCB DLBCL did not show significantly better outcome compared with non-GCB subtype patients (P=0.96; P=0.27). More importantly, after lenalidomide treatment, the patients with non-GCB DLBCL did not show significantly worse progression-free survival (PFS) and overall survival (OS) compared with GCB subtype. Lenalidomide as treatments for DLBCL patients, non-GCB DLBCL patients did not show significantly worse prognosis compared with GCB DLBCL. PMID- 26379863 TI - Matrine suppresses invasion and metastasis of NCI-H1299 cells by enhancing microRNA-133a expression. AB - Matrine has been proved to inhibit proliferation and induce apoptosis of human lung cancer cells. However, less studies involved in evaluating the effects and mechanism of matrine in cell migration and invasion of lung cancer. This study was aim to investigate the involvement of miR-133a in matrine's anti-invasion and anti-metastasis in lung cancer. MTT assay was used to assess the inhibition of proliferation effects of matrine in NCI-H1299 cells. Migration and invasion abilities of NCI-H1299 cells were investigated by Transwell assays. Expression of miR-133a was detected by real-time PCR. Anti-miR technique was applied to inhibit miR-133a in matrine treated HCI-H1299 cells. Real-time PCR and Western blotting were performed to evaluate the activation of EGFR/Akt/MMP-9 pathway. As results, matrine treatment significantly inhibited proliferation, migration and invasion of NCI-H1299 cells in a concentration-dependent manner, accompanied by significantly elevation of miR-133a expression. However, matrine failed to inhibit the metastatic ability when cells transfected with anti-miR-133a. Matrine treatment also suppressed activation of EGFR/Akt/MMP-9 pathway. The inhibitory effects of matrine on activation of EGFR pathway were also reversed by anti-miR 133a transfection in NCI-H1299 cells. In conclusion, matrine inhibited the invasion and metastasis of lung cancer cell by elevating expression of miR-133a which further suppressed activation of EGFR/Akt/MMP-9 pathway. PMID- 26379864 TI - Rapamycin, an mTOR inhibitor, induced apoptosis via independent mitochondrial and death receptor pathway in retinoblastoma Y79 cell. AB - Rapamycin is helpful in the treatment of certain cancers by inhibiting mTOR (mammalian target of rapamycin) pathway. Here, rapamycin mediated apoptosis were investigated in human retinoblastoma Y79 cells. The MTT assay showed that the IC50 value of rapamycin against Y79 cells was 0.136 +/- 0.032 MUmol/L. Flow cytometry analysis indicated that the percentage of apoptotic cells was increased from 2.16 +/- 0.41% to 12.24 +/- 3.10%, 20.16 +/- 4.22%, and 31.32 +/- 5.78% after 0.1, 0.2, and 0.4 MUmol/L rapamycin or without rapamycin treatment for 48 hours. Flow cytometry analysis showed that rapamycin induced mitochondrial membrane potential (?Psim) collapse in Y79 cells in a concentration-dependent manner. Western blot assay showed that rapamycin led to release of cytochrome c from mitochondrial membranes to cytosol. Further Western blot assays showed that rapamycin induced activation of caspase-9 and caspase-8 and the cleavage of caspase-3. Rapamycin induced cleavages of caspase-3 and apoptosis was inhibited by both Z-LETD-FMK and Z-IETD-FMK treatment. Together, all these results illustrated that rapamycin induced apoptosis in human retinoblastoma Y79 cells involvement of both intrinsic and extrinsic pathways. PMID- 26379865 TI - Methylation of sodium iodide symporter promoter correlated with aggressiveness and metastasis in papillary thyroid carcinoma: a meta-analysis. AB - BACKGROUND: Methylation of sodium iodide symporter promoter has been reported to increase the incidence of papillary thyroid carcinoma (PTC). In this meta analysis stratified via methylation of sodium iodide symporter promoter, we evaluate the relationship between methylation of sodium iodide symporter promoter and PTC. The association between methylation with aggressiveness and metastasis potential of PTC is also discussed. METHODS: We searched electronic databases for original articles and references of included studies both in English and Chinese from 1966 to 2014. Two reviewers selected the case-control study and extracted data from relevant literature independently. RESULTS: Seven articles, including 360 cases and 268 controls, were involved in this meta-analysis. The prevalence of PTC in patients with methylated sodium iodide symporter promoter was significantly higher than those with non-methylated promoter (OR=7.36, 95% CI: 4.25-12.74, P<0.001). Stratified analysis showed that PTC patients with multiple lesions, capsule invasion and lymphatic metastasis had significantly higher rates of methylation (OR=2.22, 95% CI: 1.12-4.41, P=0.02; OR=2.14, 95% CI: 1.12-4.08, P=0.02; OR=3.56, 95% CI: 1.97-6.46, P<0.0001). But no relationship was found among the methylation of sodium iodide symporter and age, gender and size of tumor. CONCLUSIONS: The methylation of sodium iodide symporter promoter is related with PTC and its aggressive and metastatic potential. Due to the limited sample size, more clinical researches should be taken in the future. PMID- 26379866 TI - Experimental study of doxorubicin interventional chemotherapy in the treatment of rabbit VX2 renal transplantation carcinoma. AB - OBJECTIVE: This study aims to explore the effect of doxorubicin interventional chemotherapy on rabbit VX2 renal transplantation carcinoma and its mechanism. METHODS: Thirty healthy New Zealand white rabbits were chosen to establish VX2 renal transplantation carcinoma models. The experimental rabbits were randomly divided into three groups with 10 rabbits in each group. The rabbits in the control group (negative control), doxorubicin group and cisplatin group were treated with saline, 5 mg/kg doxorubicin and 2 mg/kg cisplatin respectively. The tumor volume was monitored with B-mode ultrasonography. The rabbits were anesthetized and killed after two weeks of interventional chemotherapy. The changes of Bcl-2 and Bax at the levels of mRNA and protein were analyzed with real-time PCR and immunohistochemistry. RESULTS: The efficacy of interventional chemotherapy was evaluated with tumor volume changes monitored by B-mode ultrasonography. The tumor volume of control group and doxorubicin group was 1.29+/-0.60 cm(3) and 0.47+/-0.12 cm(3) respectively. Further fluorescence quantitative PCR detection results showed that doxorubicin could reduce the Bcl-2 expression and increase the Bax expression (P < 0.05). The result of immunohistochemistry was consistent with that of fluorescence quantitative PCR. CONCLUSIONS: The effect of doxorubicin interventional chemotherapy on renal transplantation carcinoma is obvious and the mechanism may be related to the down regulation of Bcl-2 expression and up-regulation of Bax expression thus inducing the apoptosis of tumor cells. PMID- 26379867 TI - Lymphocyte CD64 increased in patients with chronic HBV infection. AB - CD64 was up-regulated in infection diseases, but there was no report about the change of CD64 in chronic hepatitis B virus (HBV) infection. The purpose of this study was to determine whether there was a dynamic change of CD 64 index and to judge the value to antiviral treatment. 96 CHB patients were enrolled and selected 33 healthy adults as control. We detected the level of CD64, found the level of CD64 were significantly increased in chronic HBV infection patients, especially the lymphocyte CD64 (8.12 +/- 0.23 vs. 6.25 +/- 0.27; P < 0.001). Further, we proved CD64 index was increased in various stages of chronic HBV infection. ROC curve analysis showed the level of lymphocyte CD64 had higher AUC value than neutrophil or monocyte. Then we monitor longitudinally the impact of the treatment with interferon-alpha and found that the suppression of viral replication induced by interferon-alpha resulted in a decrease in CD64 index. In conclusion, this study showed that CD64 index was increased in chronic HBV infection patients and changed with the course of disease, the therapy of interferon-alpha would correct it, and analysis prompted that the level of lymphocyte CD64 would be more suitable for as a biomarker to judge the condition of chronic HBV infection and the curative effect of interferon-alpha treatment. PMID- 26379868 TI - A new surgical method for penile girth enhancement. AB - OBJECTIVE: We developed a new surgical model of penile girth enhancement in dog, with minimal damage, fewer complications, and high success rate, to enable the experimental investigation of penile implants. METHODS: We obtained materials for penile girth enhancement by processing the pericardium and blood vessel wall collected from pigs. Incisions were made at the penile bulb for the implantation of the materials, and facilitate observation and data collection, based on the anatomical features of dog's penis. We measured the girth of the flaccid penis before and after the operation, and erectile function at 1-month postoperation. In addition to evaluation of recovery from the incision and local pathological changes, ultrasonic examination was performed to monitor the long-term changes associated with implantation. RESULTS: The mean girth of the flaccid penis significantly increased from 7.37+/-0.40 cm before the operation, to 8.70+/-0.56 cm postoperation. Dogs resumed normal mating at 1 month after the operation, without any significant change in the mating time. Ultrasonic examination clearly illustrated the implants, and helped in the measurement of the distance between the materials and the baculum. CONCLUSION: Chinese Rural dog is a promising animal model for penile girth enhancement surgery. The findings demonstrated that surgical implantation into penile bulb was associated with less damage, faster postoperative recovery, and higher success. For the first time, ultrasonic examination provided objective data on the surgical outcomes of penile girth enhancement. PMID- 26379869 TI - Cauda equina syndrome: an uncommon symptom of aortic diseases. AB - BACKGROUND: In order to help diagnose and deal with the fetal aortic diseases in time, we retrospectively reviewed 8 patients who presented with cauda equina syndrome (CES) but actually suffered from low spinal nerve ischemia due to aortic diseases. MATERIAL AND METHODS: 8 patients were initially diagnosed as CES. 7 patients were confirmed with aortic diseases. 1 patient was confirmed with aortic saddle embolism post emergent laminectomy. Relief of CES symptoms was evaluated during preoperation and follow-up period. RESULTS: 1 patient was diagnosed as aortic dissection and 5 patients as AAA. These 6 patients underwent endovascular aortic repair (EVAR). The CES was relieved in 5-10 d post procedure. The 7th patient was diagnosed with acute abdominal aortic occlusion and then underwent catheter directed thrombolysis with recombinant tissue plasminogen activator (rTPA) for 20 h and CES disappeared. The JOA scores of the 7 patients were recovered from preoperative 15.14+/-1.21 to 21.00+/-2.16 within 5-10 d (P<0.01), and evaluated to be 24.12+/-1.34, 25.88+/-1.21 and 26.29+/-1.11 at 3 m-, 6 m- and 12 m-follow-up point, respectively. The 8th patient was initially diagnosed as lumbar spinal stenosis and lumbar disc herniation. The patient underwent emergent vertebral canal decompression and presented with serious CES symptoms. CTA confirmed that the patient had been suffered from aortic saddle embolism (ASE). CONCLUSION: CES caused by abdominal aortic diseases is a special event with fetal consequences if it is not recognized and treated promptly. Orthopedists and neurosurgeons should pay attentions particularly to this issue to preserve the cauda equina functions to their maximums. PMID- 26379870 TI - Aldehyde dehydrogenase 2 (ALDH2) Glu504Lys polymorphism is associated with hypertension risk in Asians: a meta-analysis. AB - BACKGROUND: The association of the aldehyde dehydrogenases-2 (ALDH2) Glu504Lys polymorphism and hypertension in Asians has been investigated. This meta-analysis aims to comprehensively assess the influence of this polymorphism on the hypertension risk. METHOD: An electronic literature search was conducted using the following database: PubMed, Embase and China National Knowledge Infrastructure (CNKI) till to Mar 25th, 2015. The strength of the association between statins and fractures risk was calculated with the OR and respective 95% CIs. The random effect model was used. RESULTS: Nine studies evaluating the relationship between ALDH2 Glu504Lys polymorphism and hypertension risk in Asians were selected in this meta-analysis. A total of 12161 subjects were included. The data showed that ALDH2 Glu504Lys polymorphism could increase the risk of hypertension of Asians (OR = 1.31; 95% CI, 1.18-1.47; P < 0.00001). In the subgroup analysis of race, both Japanese and Chinese with ALDH2 Glu504Lys polymorphism showed increased hypertension risk (OR = 1.23; 95% CI, 1.09-1.38; P = 0.0006 and OR = 1.46; 95% CI, 1.21-1.77; P = 0.0001), respectively. In the subgroup analysis of gender, males with this polymorphism showed increased hypertension risk (OR = 1.59; 95% CI, 1.40-1.80; P < 0.00001). However, females did not showed this result (OR = 0.94; 95% CI, 0.69-1.30; P = 0.71). When considered alcohol consumption, we found that drinkers and non-drinkers all had increased hypertension risk, if they carried this polymorphism. CONCLUSION: This meta-analysis suggested that ALDH2 Glu504Lys polymorphism was a risk factor of hypertension in Asians. PMID- 26379871 TI - Effects of alveolar ridge preservation on delayed implant osseointegration. AB - To evaluate the effects of alveolar ridge preservation with Bio-Oss bone substitute (Geistlich Pharma) on delayed implant osseointegration. The 3rd and 4th left and right mandibular premolars were extracted from four adult healthy male and female dogs. For the experimental group, we randomly selected two extraction sockets in each dog to be filled with Bio-Oss bone substitute (Geistlich Pharma). The two remaining extraction sockets remained untreated and served as the control group. Three months after Bio-Oss placement, dental implants were inserted into the alveolar bone of the experimental group and the control group. The osteogenic activity of the bone around the implants was assessed by evaluating the histological morphology and by estimating histomorphometric parameters at 3 and 6 months after delayed implantation. At 3 months, Goldner's trichrome staining analysis showed that the bone-implant contact rate and mineralised bone area around the implant were significantly higher in the experimental group (75.98% +/- 8.97% and 69.52% +/- 9.63%, respectively) than in the control group (56.13% +/- 8.18% and 52.82% +/- 7.25%, respectively; P < 0.05). However, at 6 months, the two groups showed no significant difference. Fluorescence microscopy analysis revealed that the average mineralisation apposition rate of the bone tissue around the dental implant in the experimental group at 3 and 6 months was 6.80 +/- 0.43 MUm and 8.38 +/- 0.84 MUm, respectively, which was significantly higher than the rate in the control group (P < 0.05). These data indicated that alveolar ridge preservation by using Bio-Oss placement can promote osseointegration of delayed implantation. This may be a promising option for clinical use. PMID- 26379872 TI - Microvascular invasion as a prognostic indicator in renal cell carcinoma: a systematic review and meta-analysis. AB - Microvascular invasion (MVI), an omen of potential hematogenous spread of tumor cells, has been identified as an accepted risk factor for poor prognosis in some solid tumors. But its prognostic value in renal cell carcinoma (RCC) remains disputable. In order to address this question rigorously, we performed a systematical review of the published literature on MVI and RCC prognosis. According to the PRISMA statement, we searched PubMed, Web of science, and Cochrane Library database and identified 33 cohort articles that met the eligibility criteria and involved 14,946 patients (48-2596 per study) in this meta-analysis. Using the random effects model, the association between MVI and four generally recognized end points were estimated, including cancer-specific survival (CSS), recurrence-free survival (RFS), metastasis-free survival (MFS) and overall survival (OS). The presence of MVI was detected in 14.4% of the pathological specimens. A higher incidence of MVI was associated with some acknowledged prognostic risk factors such as higher pathological TNM stages and higher tumor grades. Statistical significance of the combined hazard ratio (HR) was detected for CSS (HR, 2.090; 95% CI, 1.530-2.857), RFS (HR = 2.749; 95% CI, 1.974-3.828), MFS (HR = 1.621; 95% CI, 1.095-2.400). However, the association between MVI and worse overall survival did not address statistical significance (HR = 1.371; 95% CI, 0.978-1.923). These findings suggest that the presence of MVI has a detrimental effect on clinicopathological features of RCC and could serve as a poor prognostic factor for patient with RCC. PMID- 26379873 TI - Morphological effects of MMPs inhibitors on the dentin bonding. AB - Matrix metalloproteinases (MMPs) have been studied extensively, and MMP inhibitors have been used as dental pretreatment agents prior to dentin bonding because they reduce collagen fiber degradation and improve bonding strength. However, morphologic characteristics of the collagen network after etching and of the post-adhesive dentin hybrid layers (DHL) after MMP inhibitors pretreatment have not been evaluated. Thus, we investigated demineralized dentin pretreated with chlorhexidine (CHX) and minocycline (MI) in an etch- and -rinse adhesive system with field emission scanning electron microscopy (FESEM) and immuno-gold labeling markers to observe the collagen network and DHL. FESEM revealed after CHX and MI, a demineralized dentin surface and improved collagen network formation, reduced collagen degradation, and distinct gold-labeling signals. Applying adhesive after either MMP inhibitor created a better dentin interface as evidenced by immuno-gold staining, better adhesive penetration, and higher DHL quality. With microtensile bond strength tests (uTBS) we estimated bonding strength using uTBS data. Immediate uTBS was enhanced with MMP inhibitor application to the bonding surface, and the CHX group was significantly different than non-treated etched surfaces, but no significant change was detected in the MI group. Surface micromorphology of the fractured dentin resin restoration showed that the CHX group had a better resin and dentin tube combination. Both MMP inhibitors created uniform resin coverage. Thus, morphologic results and uTBS data suggest that CHX and MI can inhibit MMP activity, improve immediate bonding strength, and enhance dentin bonding stability with an etch- and -rinse adhesive system. PMID- 26379874 TI - Associations of polymorphisms of rs1015213 with primary angle closure glaucoma recent evidence and a meta-analysis. AB - BACKGROUND: Primary angle closure glaucoma (PACG) has been thought to have a significantly genetic basis for a long time, and genome-wide association studies (GWAS) have identified various candidate genes including PCMTD1-ST18 rs1015213 as susceptibility loci. However, different results produced inconsistent results and make the conclusions controversial in some extent. Thus, we carried out a systematic review, attempting to summarize the recent evidence and determine the association of rs1015213 with PACG risk. METHODS: A systematic literature search was conducted to identify all published studies on associations of rs1015213 (PCMTD1-ST18) polymorphism and PACG risk up to April 30, 2015. Selection of eligible studies was undertaken by two investigators according to inclusion criteria. Summary odds ratios (ORs) and 95% confidence intervals (95% CIs), as well as the pooled ocular biometric measures in different genotype or allele groups, were collected and analyzed. Heterogeneity was measured using the chi square-based Q statistic test and I(2) metric. Publication bias of the included articles was evaluated using funnel plots. RESULTS: 21 eligible studies were included, among them 15 studies with enough data to estimate OR were included for meta-analysis, with a total of 24764 subjects (4737 PACG patients and 20027 controls), including 19416 Asian subjects (4378 PACG patients and 15038 controls) and 5348 Caucasian subjects (359 PACG patients and 4989 controls). Low heterogeneity was detected among studies (for Asian subgroups P=0.80, I(2)=0%, for Caucasian subgroups P=0.78, I(2)=0%, for all groups, P=0.89, I(2)=0%), thus, only fixed-effects model was used in the meta-analysis. The results showed that the frequencies of the TT genotype of rs1015213 were significant higher in PACG group than the controls in Asians (OR=1.51, 95% CI 1.27-1.79, P<0.01) but not in Caucasians (OR=1.54, 95% CI 0.94-2.54, P=0.09). In sensitivity analysis the significance of the pooled OR remained almost the same when removing studies individually. Visual inspection of the funnel plots revealed no asymmetry. 6 studies were included for evaluating the association between rs1015213 polymorphism with axial length (AL) and anterior chamber depth (ACD), all of them showed that rs1015213 polymorphism is independent with AL (Shi, P=0.528; Day, P=0.74; Nongpiur, pooled P=0.067, respectively). 5 studies showed that rs1015213 polymorphism was significantly associated with a shallow ACD (P<0.05) but the other study did not support this result. CONCLUSION: Our meta-analysis suggests that rs1015213 (TT genotype) is associated with PACG in Asian populations, but this association is not significant in Caucasian population and need more data. Some literatures also supported that rs1015213 polymorphism was associated with a shallow ACD but not with a short AL, however the evidences are not sufficient yet. PMID- 26379875 TI - Effect of enoxaparin on clinical events after percutaneous coronary intervention. AB - OBJECTIVE: To explore the influence of enoxaparin on clinical events after percutaneous coronary intervention (PCI). METHODS: We recruited 400 patients that had undergone the percutaneous coronary intervention without complications in the Cardiology Department of Changhai Hospital consecutively from May 2011 to December 2012. The patients were randomly assigned to receive anticoagulation therapy (enoxaparin) or no anticoagulant. Patients were assessed for major adverse cardiac and cerebrovascular events (MACCEs) during hospitalization and at 1 and 12 months after PCI. RESULTS: There were no significant differences in the frequency of MACCEs between the two groups during hospitalization, at 1 month or 12 months post-PCI. During hospitalization, MACCEs occurred in 1.5% of the anticoagulation group versus 1.6% of the non-anticoagulation group (P>0.9). The groups had comparable rates of major bleeding (3.6% vs 2.1%, P=0.37), but minor bleeding was increased in the anticoagulation group (29.1% vs. 18.7%, P=0.016). At 1 month post-PCI, MACCEs occurred in 1.5% of the anticoagulation group and 2.6% of the non-anticoagulation group, (P=0.5), and at 12 months post-PCI, the rates were 5.6% vs. 6.2%, respectively (P=0.8). CONCLUSIONS: The frequency of MACCEs after PCI in the non-anticoagulation group was not significantly increased compared with that of the anticoagulation group. However, the rate of minor bleeding during hospitalization is significantly lower in non-anticoagulation group than that in anticoagulation group. The results suggest that routine anticoagulation therapy after PCI is not necessary for patients without procedure complications. PMID- 26379876 TI - Fish consumption doesn't reduce the risk of hepatocellular carcinoma. AB - BACKGROUND: Several observational studies have investigated the association between fish consumption and the risk of hepatocellular carcinoma (HCC), however, the results were inconsistent. Hence, we performed a meta-analysis of observational studies to evaluate the effect of fish consumption on HCC risk. METHODS: A systematic search was performed using the Pubmed, Embase, and Cochrane Library Central database for case-control and coshort studies that assessed fish intake and HCC risk. Fixed-effect and random-effect models were used to estimate summary relative risks (RR) and the corresponding 95% confidence intervals (CIs). Subgroup analyses and sensitivity analysis were also performed. RESULTS: Nine case-control studies and three cohort studies were included, involving a total of 1,071,458 participants and 2,627 HCC cases. Meta-analysis showed that there was no association between fish consumption and a significant reduction in HCC incidence (RR = 0.85, 95% CI [0.62, 1.17]). In our subgroup analyses, the result was substantially affected by adjustment for hepatic viruses' infection status. Sensitivity analysis confirmed the stability of results. Furthermore, there was no evidence of publication bias as suggested by Begg's P value (P = 0.411) and Egger's (P = 0.596) test. CONCLUSIONS: In conclusion, our results do not support a significant inverse association of fish consumption with HCC risk. More in depth studies are warranted to report more detailed results, including stratified results by fish types, preparation methods, and gender. PMID- 26379877 TI - Chemotherapy-induced neutropenia during adjuvant treatment for cervical cancer patients: development and validation of a prediction model. AB - An artificial neuron network (ANN) model combining both the genetic risk factors and clinical factorsmay be effective in prediction of chemotherapy-induced adverse events. PURPOSE: To identify genetic factors and clinical factors associated with bone marrow suppression in cervical cancer patient, and to build a model for chemotherapy-induced neutropenia prediction. METHODS: We performed a genome wide association study on a cohort to identify genetic determinants. Samples were genotyped using the Axiom CHB 1.0. The primary analyses focused on the scan of 657178 single-nucleotide polymorphisms (SNPs). Artificial neural network were used to integrating clinical factors and genetic factors to predict the occurrence of neutropenia. RESULTS: 32 variants associated with neutropenia in the patients after chemotherapy were found (P<1 * 10(-4)). During internal validation and external validation, artificial neural network performed well in predicting neutropenia with considerable accuracy, which is 88.9% and 81.7% respectively. ROC analysis had acceptable areas under the curve of 0.897 for the internal validation sample and 0.782 for the external validation sample. CONCLUSION: Neutropenia may be associated with both genetic factors and clinical factors. Our study found that the artificial neural networks model based on the multiple risk factors jointly, can effectively predict the occurring of neutropenia, which provides some guidance before the starting of chemotherapy. PMID- 26379878 TI - The association between MMP-12 82 A/G polymorphism and susceptibility to various malignant tumors: a meta-analysis. AB - Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases responsible for degrading essentially all components of the extracellular matrix (ECM). Accumulating evidence suggests that MMPs might play a critical role in growth, invasion, and metastasis of malignant tumors. A single nucleotide polymorphism (SNP) in the promoter region of MMP-12, MMP-12 82 A/G (rs2276109), has been recognized to play a critical role in regulating the expression of MMP 12, however, its correlation with tumor susceptibility remains controversial. To address this issue, we performed meta-analysis to investigate the association MMP 12 82 A/G polymorphism and susceptibility of nine malignant tumors from 11 studies, including 6153 cancer patients and 6838 controls. Two reviewers independently screened studies for eligibility and extracted data for included studies. While overall no evident association between MMP-12 82 A/G and tumor susceptibility was observed, subgroup analysis revealed a specific role of G allele in increasing the susceptibility for epithelial ovarian carcinoma (EOC) using the allele model (fixed effects OR = 2.45, 95% CI = 1.46-4.10, P = 0.001) and the dominant model (fixed effects OR = 2.52, 95% CI = 1.49-4.24, P = 0.001). We thus suggest that G allele of MMP-12 82 A/G polymorphism is a genetic risk factor for EOC. PMID- 26379879 TI - Identification of low miR-105 expression as a novel poor prognostic predictor for human glioma. AB - Glioma is the most common and aggressive brain tumor with poor clinical outcome. Identification and development of new biomarkers could be beneficial for diagnosis and prognosis of glioma patients. Recent studies have showed evidences that dysregulation of microRNAs (miRNAs) is involved in glioma tumorigenesis. Therefore, we attempted to identify specific miRNAs as prognostic and predictive markers for glioma. We statistically compared expression profile of 365 miRNAs between WHO grade IV and grade III gliomas, by qRT-PCR. MiR-105 was identified as a remarkably decreased miRNA in grade IV gliomas compared with grade III gliomas (P=0.012, fold change =0.04). We subsequently examined its expression levels in an independent series of gliomas, and statistically analyzed the associations between miR-105 expression and clinicopathological characteristics and survivals of these glioma patients. MiR-105 showed remarkably decreased expression in gliomas as compared to non-neoplastic brains. And grade IV gliomas had significantly lower miR-105 expression compared with grade III and II gliomas (both P<0.001). Additionally, low miR-105 expression was statistically associated with advanced tumor grade, advanced patient's age and low pre-operative Karnofsky performance score (all P<0.001). Furthermore, patients with low miR-105 expression had significantly poorer survival by Kaplan-Meier method (P<0.001). Multivariate analysis indicated miR-105 as an independent prognostic indicator for glioma patients (P=0.018, risk ratio =4.2). Our results suggested that low expression of miR-105 may correlate with unfavorable clinical outcome and be involved in tumorigenesis and aggressive progression of glioma. And miR-105 may be a novel biomarker in prognostic prediction for glioma. PMID- 26379880 TI - Combination of propranolol and sclerotherapy for treatment of infantile parotid hemangiomas. AB - We aimed to evaluate the efficacy of combination of propranolol and sclerotherapy in treating parotid hemangiomas. Twenty-six parotid hemangiomas patients were subjected to combined treatment from January 2009 and June 2014. The effects of the therapy modality were evaluated. Nineteen patients were females and 7 were males. The median age of treatment initiation was 4.96 months. Twelve lesions were located on the left side parotid glands, while thirteen lesions affected the right side. One infant had bilateral lesions. One to six (average 2.04) injections were performed and the mean period for propranolol was 8.94 months. All the patients got satisfied aesthetic outcomes. No complications of propranolol or sclerotherapy occurred during the whole medication period. The study demonstrated that combination of propranolol and sclerotherapy was an effective and safe method for infantile parotid hemangiomas. Larger-scale studies should be performed to further investigate the long-term efficacy and results of the present combined method for infantile parotid hemangiomas. PMID- 26379881 TI - Differential expression of T cell-related genes in AMI and SA stages of coronary artery disease. AB - OBJECTIVE: To identify differentially expressed T cells-related genes in peripheral blood mononuclear cells and compare their differences in T cell activation and subset functions in different stages of coronary atherosclerosis disease (CAD). METHODS: 20 patients with acute myocardial infarction patients (AMI), 20 patients with stable angina pectoris (SA) and 20 healthy volunteers were recruited into the study. Whole human genome microarray analysis was used to detect the expression of T cell related genes among three groups. RESULTS: mRNA expression of 68 genes involved in T cell was detected. 1) Antigen recognition: in the AMI patients 12 genes were down-regulated and 9 were significantly down regulated among all 13 genes, compared with those of the SA and the control group, respectively. 2) Co-stimulators and regulators of T cell activation: among 16 genes in the AMI patients, 15 genes were lower and 8 were significantly lower than the other two groups. 3) T cell subsets, CTL: all 11 genes in the AMI patients were down-regulated, particularly GZMM and CASP8 were significantly down regulated compared with the SA patients and controls. Th1/Th2: in the AMI patients, gene expressions including IL1 and IL18 were significantly higher, whereas GATA3 mRNA was significantly lower than those in other two groups. Th17/Treg: in the AMI group, RORC and CCR6 mRNAs were significantly down regulated compared with the control group, while CD25 and CD127 expressions were significantly lower than SA group. There was no difference in T cell related genes between the SA patients and the controls. CONCLUSIONS: In the AMI patients, the mRNA expression of T cell antigen recognition, activation and subset functions was imbalanced or decreased, indicating the dysfunction of cellular immunity in patients with AMI. Then improving T cell mediated cellular immunity may be considered as a potential target for medical interventions in the patients with AMI. PMID- 26379882 TI - An event-related potentials study on the attention function of posttraumatic stress disorder. AB - OBJECTIVE: In order to examine the functional defects and attentional bias in post-traumatic stress disorder (PTSD) patients, event-related potentials (ERP) of attention was investigated. METHODS: Three groups of emotion pictures, positive, negative (or violent) and neutral, were viewed by 19 PTSD patients and 15 normal controls. Each picture had a frame, and participants reacted to the color of the frame by clicking buttons. Electroencephalogram (EEG) and behavior data were recorded. Peak latencies and amplitudes of P2 were measured. RESULTS: For the three groups of pictures, PTSD patients had longer reaction time than the controls. Significant difference was found between PTSD patients and controls in response to violent, positive and neutral pictures. PMID- 26379883 TI - Pycnogenol((r)) treatment inhibits bone mineral density loss and trabecular deterioration in ovariectomized rats. AB - CONTEXT: Pycnogenol((r)) extracted from French maritime pine bark (Pinus pinaster Ait. subsp. atlantica) is functional for its antioxidant activity. OBJECTIVE: To investigate the effects of Pycnogenol((r)) on bone mineral density (BMD), trabecular microarchitecture and bone metabolism in ovariectomized (OVX) rats. MATERIALS AND METHODS: Thirty Sprague-Dawley rats were randomized into 3 groups: SHAM group (sham-operated rats), OVX group (OVX rats), and treatment group (OVX rats supplemented with 40 mg/kg Pycnogenol((r)) by oral gavage). Serum levels of procollagen type I N-terminal propeptide (PINP), alkaline phosphatase (ALP) and minerals were detected at the end of 9 weeks of gavage. Deoxypyridinoline/creatinine (DPYD/Cr) and N-telopeptide of type I collagen/creatinine (NTX/Cr) rate in urine were also calculated. Left femora were collected for BMD determination, and the right distal femora were made into undecalcified specimens for histomorphometry analysis. RESULTS: At the end of study, PINP level, DPYD/Cr and NTX/Cr rate were significantly increased, and femoral BMD were dramatically decreased in OVX group compared with SHAM group (P < 0.01) while serum minerals and ALP concentrations showed no significant difference. The treatment group had dramatically decreased biomarkers and increased BMD than OVX group (P < 0.01). Histomorphometry analysis showed worse bone microarchitecture parameters in the OVX group compared with the SHAM group which were significantly improved in the treatment group compared with the OVX group (P < 0.01). DISCUSSION AND CONCLUSION: Pycnogenol((r)) (40 mg/kg) can inhibit aggravated bone resorption, prevent BMD loss, and restore the impaired trabecular microarchitecture in OVX rats after 9-week-intervention. PMID- 26379884 TI - Celecoxib can suppress expression of genes associated with PGE2 pathway in chondrocytes under inflammatory conditions. AB - This study aimed to investigate the effect of a selective cyclooxygenase-2 (COX 2) inhibitor (celecoxib) on the expression of arachidonate-associated inflammatory genes in cultured human normal chondrocytes. Normal chondrocytes were obtained from the cartilage of three different amputated patients without osteoarthritis (OA). Affymetrix Human microarray was used to assess the alterations in gene expression in three groups of cells: untreated cells (negative control group), cells treated with interleukin-1beta (IL-1beta) (positive control group), and cells treated with IL-1beta and celecoxib. The patterns of up-regulation and down-regulation of gene expression were further validated by real-time PCR. A total of 1091 up-regulated genes and 1252 down regulated genes were identified in the positive control group compared with the negative control group. Among them, PTGS2, ADAMTS5, PTGER2, mPTGES and PTGER4 are known to be involved in chondrocyte inflammation, while VEGFA, BCL2, TRAF1, CYR61, BMP6, DAPK1, DUSP7, IL1RN, MMP13 and TNFSF10 were reported being associated with cytokine and chemokine signaling. 189 up-regulated genes and 177 down-regulated genes were identified in the positive control group compared with intervention group. PTGS1, PTGS2, ADAMTS5, PTGER2, mPTGES and PTGER4 were among the genes down-regulated upon the treatment with celecoxib. Our results demonstrated that the OA chondrocytes are the site of active eicosanoid production. IL-1beta can activate inflammation in chondrocytes and trigger the production of various proteins involved in cyclooxygenase pathway. The expression of genes corresponding to these proteins can be down-regulated by celecoxib. The findings indicate that the therapy with prostaglandin E2 (PGE2)-blocking agents may decrease the PGE2 production not only by direct inhibition of COX-2 activity, but also by down-regulating the expression of genes encoding for COX-2, microsomal prostaglandin-endoperoxide synthase 1 (mPGES-1) and prostaglandin E receptors 4 (EP4) in the articular chondrocytes. PMID- 26379885 TI - Physical training improves body weight and energy balance but does not protect against hepatic steatosis in obese mice. AB - This study sought to determine the role of physical training (PT) on body weight (BW), energy balance, histological markers of nonalcoholic fatty liver disease (NAFLD) and metabolic gene expression in the liver of ob/ob mice. Adult male ob/ob mice were assigned into groups sedentary (S; n = 8) and trained (T; n = 9). PT consisted in running sessions of 60 min at 60% of maximal speed conducted five days per week for eight weeks. BW of S group was higher from the 4(th) to 8(th) week of PT compared to their own BW at the beginning of the experiment. PT decreased daily food intake and increased resting oxygen consumption and energy expenditure in T group. No difference was observed in respiratory exchange ratio, but the rates of carbohydrate and lipids oxidation, and maximal running capacity were greater in T than S group. Both groups showed liver steatosis but not inflammation. PT increased CPT1a and SREBP1c mRNA expression in T group, but did not change MTP, PPAR-alpha, PPAR-gamma, and NFKB mRNA expression. In conclusion, PT prevented body weight gain in ob/ob mice by inducing negative energy balance and increased physical exercise tolerance. However, PT did not change inflammatory gene expression and failed to prevent liver steatosis possible due to an upregulation in the expression of SREBP1c transcription factor. These findings reveal that PT has positive effect on body weight control but not in the liver steatosis in a leptin deficiency condition. PMID- 26379886 TI - A novel two-dimensional quantitative shear wave elastography for differentiating malignant from benign breast lesions. AB - OBJECTIVE: The purpose of this study was to evaluate the diagnostic performance of a novel quantitative shear wave elastography (SWE) of virtual touch tissue imaging quantification (VTIQ) in diagnosis of breast lesions. METHODS: The conventional ultrasound (US) and VTIQ images of 133 pathologically proven breast lesions in 98 patients were assessed. The breast lesions were classified by US breast imaging reporting and data system (BI-RADS) category. The maximum, minimum, mean and median shear wave velocity (SWV) values on VTIQ in the lesions were obtained. The area under the receiver operating curve (AUC) was computed. RESULTS: Twenty-six of 133 lesions were malignant and 107 were benign. The sensitivity and specificity for US BI-RADS assessment were 96.2% and 62.6% respectively. The SWVs in malignant lesions were all significantly higher than those in benign ones (all P < 0.001). The AUC for mean SWV value was slightly higher than AUC for maximum, minimum and median SWV values, whereas no significant differences among them were found (all P > 0.05). The cut-off value of mean SWV was 3.68 m/s, with associated sensitivity and specificity of 93.3% and 79.4% respectively. CONCLUSION: The novel quantitative SWE of VTIQ is helpful in differentiating breast lesions. Adding the quantitative SWE of VTIQ to the US BI-RADS assessment improves the specificity in diagnosing breast lesions without loss of sensitivity. PMID- 26379887 TI - Polymorphism in epidermal growth factor is related to clinical outcomes of metastatic colorectal cancer patients treated with cetuximab: a systematic review and meta-analysis. AB - Numerous studies focusing on genetic variants in order to find cetuximab subpopulation biomarkers have emerged, yet the significance of each biomarker is diverse. Based on these results, we carried out a meta-analysis to assess the correlation between epidermal growth factor (EGF) A61G polymorphism and clinical outcomes of metastatic colorectal cancer (mCRC) patients treated with cetuximab. We aim to prove that EGF polymorphisms may be potential biomarkers for cetuximab therapeutic strategies. We identified 6 previously published studies including 569 patients treated with cetuximab-based regimens. Outcomes included clinical response, progression-free survival (PFS), and overall survival (OS). GG homozygote showed association with better response rates (GG vs. AA+AG, OR = 2.82; 95% CI = 1.58-5.04) and than AA+AG genotypes. This meta-analysis showed that mCRC patients harboring GG genotype of EGF A61G polymorphism inclined to have a better response rate with cetuximab treatment. PMID- 26379889 TI - Value of sequential 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in prediction of the overall survival of esophageal cancer patients treated with chemoradiotherapy. AB - This study is to investigate the value of the metabolic parameters measured by sequential FDG PET/CT in predicting the overall survival of patients with esophageal squamous cell carcinoma (ESCC). A total of 160 patients who were newly diagnosed as ESCC patients and treated with chemoradiotherapy were included in this study. The FDG PET/CT was carried out prior to radiotherapy (PET1), when the cumulative dose of radiotherapy reached 50 Gy (PET2), at the end of radiotherapy (PET3) and 1 month after radiotherapy (PET4). The max of the standard uptake value (SUVmax) of the primary tumor, the metabolic tumor volume (MTV) and the total lesion glycolisis (TLG) prior to treatment were measured. The correlation of the measured parameters and the derived parameters of SUVmax with the overall survival was analyzed. The relatively reduced percentage of the SUVmax of PET3 and PET4 to the SUVmax of PET1 and PET2, had predictive value for the overall survival. The area under researcher operation curve (ROC) was between 0.62 and 0.73 (P < 0.01). The MTV and TLG prior to treatment might be used to predict the overall survival, and the area under ROC were both 0.69 (P < 0.001). Sequential FDG PET/CT scanning is useful to predict the overall survival of chemoradiotherapy for ESCC. The metabolic parameters and the derived parameters of FDG PET/CT have predictive values for overall survival. PMID- 26379888 TI - Reduction in pulmonary function after CABG surgery is related to postoperative inflammation and hypercortisolemia. AB - Pulmonary function is significantly reduced in the acute phase after coronary artery bypass graft (CABG) surgery. Because pulmonary function partly depends on respiratory muscle strength, we studied whether reductions in pulmonary function are related to postoperative alterations in circulatory factors that affect muscle protein synthesis. METHODS: Slow vital capacity (SVC) was assessed in 22 subjects before and 9 +/- 3 days after CABG surgery. Blood testosterone, cortisol, insulin-like growth factor-1 (IGF-1), growth hormone, sex-hormone binding globulin (SHBG), glucose, insulin, c-peptide, c-reactive protein (CRP) content, and free androgen index, cortisol/testosterone ratio, HOMA-IR index were assessed before surgery and during the first three days after surgery. Intubation, surgery time and cumulative chest tube drainage were measured. Correlations between changes in SVC and blood parameters after surgery or subject characteristics were studied. This was a prospective observational study. RESULTS: After CABG surgery SVC decreased by 37 +/- 18% (P < 0.01). Free androgen index, blood SHBG, testosterone and IGF-1 content decreased, while HOMA-IR index, cortisol/testosterone ratio, blood growth hormone, insulin and CRP content increased (P < 0.0025) in the first three days after surgery. Decrease in SVC was independently (P < 0.05) related to higher preoperative SVC (SC beta = 0.66), and greater increase in blood cortisol (SC beta = 0.54) and CRP (SC beta = 0.37) content after surgery. CONCLUSIONS: Larger reductions in pulmonary function after CABG surgery are present in patients experiencing greater postoperative increases in blood CRP and cortisol levels. Decrements in pulmonary function after CABG surgery are, at least in part, thus related to alterations in circulatory factors that affect muscle protein synthesis. PMID- 26379890 TI - Acoustic radiation force impulse induced strain elastography and point shear wave elastography for evaluation of thyroid nodules. AB - The aim of the study was to evaluate the diagnostic performance of acoustic radiation force impulse (ARFI) induced strain elastography (SE), point shear wave elastography (p-SWE), and their combined use in differentiating thyroid nodules. This retrospective study included 155 thyroid nodules (94 benign and 61 malignant) in 136 patients. Ultrasound, ARFI-induced SE and p-SWE were performed on each nodule. Receiver operating characteristic curve (ROC) analyses were performed to assess the diagnostic efficacy of ARFI-induced SE, p-SWE and their combined use to distinguish benign from malignant thyroid nodules with histological results used as the reference standard. The areas under the ROC for ARFI-induced SE, p-SWE, and their combined use were 0.828, 0.829, and 0.840, respectively (both P > 0.05). The specificity of ARFI-induced SE was higher than that of p-SWE as well as their combined use (both P < 0.05). The combination of the two methods significantly improved the diagnostic sensitivity and NPV compared with either ARFI-induced SE or p-SWE alone (both P < 0.05). For nodules <= 10 mm, the combination of the two methods significantly improved the diagnostic sensitivity only. For nodules > 10 mm, there were no significant differences in sensitivity and NPV among the three methods in differentiating thyroid nodules (all P > 0.05). In conclusions, ARFI-induced SE and p-SWE are both valuable tools for detecting malignant thyroid nodules. The combined use of ARFI-induced SE and p-SWE improves the diagnostic sensitivity and NPV significantly whereas ARFI-induced SE alone achieves the highest specificity. PMID- 26379891 TI - Can the peak E2/follicle ratio be a quantitative indicator of pregnancy outcomes following assisted reproductive cycles? A retrospective study. AB - As one of the limited reference parameters for the appropriate timing of human chorionic gonadotropin (hCG) priming and embryo transfer (ET), peak serum estradiol (E2) level and related parameters have been considered to be a possible marker of in vitro fertilization (IVF) outcomes. To our knowledge, few reports have investigated the correlation between the ratio of peak serum E2 to the number of follicles >= 14 mm on the day of hCG administration (i.e., the E2/fol. ratio) and the miscarriage rate (MR) in assisted reproductive cycles. In this study, a total of 1376 cycles were examined and grouped into quartiles by E2/fol. ratio. The patient characteristics, controlled ovarian hyperstimulation (COH) performance, and IVF/ICSI results were compared between the four groups. Patients were further categorized as younger than 35 years of age or 35 years of age and older. The association between the E2/fol. ratio and the implantation rate (IR) or MR was examined using the Mantel-Haenszel test for each group. We found that the E2/fol. ratio correlated with the IR and MR for women younger than 35 years of age. There was a statistically significant increase in the IR with E2/fol. ratio between 279.83 and 552.28 pg/ml, and women with an E2/fol. ratio > 552.28 pg/ml were more likely to suffer miscarriages. Our data support a role for cryopreservation of all embryos when E2/fol. ratio exceeds 552.28 pg/ml for women younger than 35 years of age. PMID- 26379892 TI - Degradation of dexamethasone by acclimated strain of Pseudomonas Alcaligenes. AB - This study is to investigate the use of microbial remediation technology for degradation of dexamethasone in polluted water. A strain of Pseudomonas Alcaligenes with the ability of dexamethasone degradation was isolated from hospital polluted water. This strain was further acclimated into a bacterial strain that could highly degrade dexamethasone. Domesticated bacterial proteins were separated by osmotic shock method and were analyzed using SDS-PAGE. Enzyme activity of dexamethasone degradation was detected by high performance liquid chromatography. Protein bands with different molecular weight were found in all regions of the bacteria and a band with molecular weight of about 100 kDa was most obvious. In intracellular and periplasmic liquid, there was a band with molecular weight of about 41 kDa. Enzyme activity mainly existed in intracellular liquid. The 41 kDa protease was purified using ammonium sulfate precipitation, DEAE-52 ion exchange column and Sephadex G-100 column. Dexamethasone and dexamethasone sodium phosphate degrading rates of the purified enzyme were 36% and 95%, respectively. The 100 kDa protein had a 19% coverage rate to TonB receptor dependent protein, with 11 peptides matching. The 41 kDa protein had a 56% coverage rate to isovaleryl coenzyme A dehydrogenase, with 5 peptides matching. The 41 kDa protein had good degradation between the temperature of 25 40 degrees C and PH value of 6.5-8.5. The enzyme kinetics equation was Ct = C0 e( 0.1769t), in accordance with the first-order kinetic equation. This study laid the foundation for further preparation of bioremediation agents for clearance of dexamethasone pollution in water. PMID- 26379893 TI - Association between VEGF -634G/C polymorphism and osteonecrosis of the femoral head susceptibility: a meta analysis. AB - BACKGROUND: VEGF plays an important role in bone formation and repair. However, the effects of VEGF -634G/C polymorphisms on the pathogenesis of osteonecrosis of the femoral head (ONFH) were not conclusive. Our research was aimed to further analyze the association of VEGF -634G/C polymorphism with ONFH risk. METHODS: The relevant articles were searched in PubMed, Elsevier, EMBASE, Web of Science and Chinese National Knowledge Infrastructure (CNKI) database. And a total of 692 cases and 875 controls were included. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the correlation of VEGF 634G/C polymorphism and ONFH susceptibility. Chi-square based Q-statistic test was used to evaluate heterogeneity among the studies. The random-effects model or fixed-effects model was used depending on heterogeneity. RESULTS: The sensitivity analysis and publication bias test indicated that our results were stable and credible. And the results suggested that VEGF -634G/C polymorphism was significantly related with increased risk for ONFH in Asian population (CC versus GG: OR=1.34, 95% CI=1.02-1.76). CONCLUSION: The results indicated that VEGF 634G/C polymorphism might serve as genetic-susceptibility factor for ONFH. PMID- 26379894 TI - Metabonomics study on Polygonum multiflorum induced liver toxicity in rats by GC MS. AB - Polygonum multiflorum, a traditional Chinese medicinal herb, is widely used in liver and liver nourishing. Recent years, drug regulatory departments reported that Polygonum multiflorum caused serious adverse reaction in clinic, especially liver injury. In this study, we detected the changes in rat serum and liver tissue metabolites through gas chromatography-mass spectrometry (GC-MS). Mass spectrometry, partial least squares-discriminate analysis (PLS-DA) and other diversified techniques were used to analyze the differences among their metabolites. Compared to the control group, the serum concentrations of L threonine and serine in water extraction groups increased. The serum concentrations of 9,12-octadecadienoic acid, hexadecanoic acid, oleic acid, D glucose and octadecanoic acid in alcohol extraction groups increased, while lactic acid decreased to a great extent. For liver tissue, compared to the control group, the concentrations of myo-inositol, oleic acid and cholesterol in water extraction groups increased, while those of hexadecanoic acid, octadecanoic acid, ribitol and butanedioic acid decreased to a great extent. The concentrations of myo-inositol, phosphoric acid, uridine, oleic acid, cholesterol and butanoic acid in alcohol extraction groups increased to a great extent, while those of hexadecanoic acid, octadecanoic acid, ribitol and butanedioic acid decreased. The results indicate that Polygonum multiflorum induces the metabolic disorders of energy metabolism, amino acid and lipid metabolism. What's more, liver injury of alcohol extraction group was more serious than group of water extraction. PMID- 26379895 TI - Association analysis of selenoprotein S polymorphisms in Chinese Han with susceptibility to gastric cancer. AB - OBJECTIVE: selenoprotein S (SelS) gene polymorphism is closely related to a variety of malignant tumours. Here, we evaluate the association between SelS polymorphism and genetic susceptibility to gastric cancer. METHODS: A case control study was conducted to investigate the role of two SelS single nucleotide polymorphisms (SNPs) on the susceptibility to gastric cancer. The genotypes and genotype frequencies of the SelS were determined in 260 gastric cancer patients and 278 age-matched healthy controls. Polymerase chain reaction restriction fragment length of polymorphism (PCR-RFLP) was taken to genotype rs28665122 (G 105A) and rs34713741 (G-254A) within the SelS gene. The differences in the genotypic distribution between gastric cancer patients and healthy controls were analyzed with the Chi-square test for trends. Logistic-regression analysis was used to estimate odds ratios (OR) and 95% confidence intervals (CI), adjusting for age and sex. RESULTS: For rs34713741 in SelS, the allele frequencies analysis indicated that the allele frequency of the T was higher in patients than in controls (P=0.001). There were significant differences of genotype frequencies and allele of rs34713741 polymorphism between gastric cancer group and control group (P<0.05). The relative risk of suffering from gastric cancer in T allele was 1.62 times of CC genotype in Hunan Han population (OR=1.62, 95% CI: 1.15~2.29). But there were no differences of genotype frequencies and allele of SelS rs28665122 polymorphism between gastric cancer group and control group. CONCLUSIONS: Allele T of SelS rs34713741 polymorphism is significantly associated with an increased risk of gastric cancer in Chinese population. PMID- 26379896 TI - Topical use of olive oil preparation to prevent radiodermatitis: results of a prospective study in nasopharyngeal carcinoma patients. AB - BACKGROUND: Radiodermatitis is a common side effect of radiotherapy. However, an effective method for the prevention of radiodermatitis has not yet been identified. The purpose of this study was to evaluate the effectiveness of topical olive oil in the prevention of acute radiodermatitis in patients with nasopharyngeal carcinoma (NPC) who were undergoing concurrent chemoradiotherapy. METHODS: A prospective study was conducted in patients with NPC. The patients were randomized into the intervention (n = 47) and control (n = 47) groups. Patients in the control group were treated with a general skin care regimen (placebo), whereas patients in the intervention group were treated with olive oil thrice daily for 7 weeks during chemoradiotherapy and for two weeks thereafter. On a weekly basis for a total duration of 9 weeks, a blinded observer assessed the severity of dermatitis, which was graded from 0 to 4 according to the Radiation Therapy Oncology Group (RTOG) criteria and the Visual Analog Scale (VAS) score. RESULTS: Mild reactions due to radiation (grades I and II) occurred in 93.6% of the intervention group and in 72.3% of the control group. Patients in the intervention group encountered significantly less severe dermatitis during chemoradiotherapy compared with patients in the control group (P < 0.01). A multivariate analysis revealed that the use of olive oil (P < 0.01) was significantly associated with a decrease in skin injuries. CONCLUSIONS: The prophylactic use of olive oil was associated with a significant decrease in the intensity of acute dermatitis in NPC patients. The results of this trial indicate that olive oil holds promise as a safe and effective prophylactic treatment for radiodermatitis. PMID- 26379897 TI - Relevance of plasma malondialdehyde level and severity of portal hypertension in cirrhotic patients. AB - BACKGROUND: Portal hypertension is one of the death reasons for the liver cirrhosis patients. The oxidative stress is related to the occurrence and development of portal hypertension in cirrhosis. Malondialdehyde (MDA), one of the lipid peroxides, increases substantially in cirrhotic patients. AIMS: To evaluate the relevance between the MDA level and portal hypertension in cirrhotic patients. METHODS: 60 liver cirrhotic patients and 30 healthy controls were enrolled. The plasma MDA level and general blood tests including ALT, AST, ALB, total bilirubin, and platelet were measured. All people enrolled accepted endoscopic examination and B-Ultrasound check to evaluate the severity of portal hypertension. RESULTS: The MDA plasma level of cirrhotic patients was significantly higher than the controls (P<0.001) and increased significantly accompanied by the severity of liver fibrosis and portal hypertension (P<0.01). Further, the plasma MDA level of cirrhotic patients was significantly correlated with Child-Pugh classification of cirrhosis (r=0.820, P<0.001), the degree of esophageal varices (r=0.857, P<0.001) and the width of portal vein (r=0.652, P<0.001). The ROC curve analyses showed that the plasma MDA level is a strong predictor of liver cirrhosis and portal hypertension. CONCLUSIONS: Plasma MDA level may correlate with the severity of portal hypertension in cirrhotic patients. PMID- 26379898 TI - Risk factors of intracranial hemorrhage after brain AVM interventional therapy and its effects on prognosis. AB - OBJECTIVE: This study is to investigate risk factors of intracranial hemorrhage and their effects on prognosis in patients with brain intracranial arteriovenous malformation (AVM) after interventional therapy. METHODS: A total of 80 cases of brain AVM patients were admitted to our hospital and received interventional embolism treatment from December 2011 to July 2014. The patients all were confirmed by digital subtraction angiography. Risk factors of intracranial hemorrhage after interventional therapy were analyzed by multivariate analysis. The factors included age, sex, AVM diameter, vein drainage types, embolism area, etc. Meanwhile, the patients were followed up for 60 months after interventional embolism therapy, so as to assess the impact of related risk factors on prognosis. RESULTS: By logistic regression analysis, it was found that age, AVM diameter, AVM combined with aneurysm, embolism area and venous drainage types were related risk factors those could lead to intracranial hemorrhage. Meanwhile, it was identified by receiver operating characteristic curve that embolism area, AVM diameter and AVM combined with aneurysm were risk factors had considerable influence on prognosis while the diagnosis significance of age and venous drainage types was poor (P > 0.05). The survival curves of embolism area and AVM diameter on prognosis had been identified by Kaplan-Meier analysis and it showed that embolism area < 50% and AVM diameter >= 3 cm had a better prognosis than embolism area >= 50% and AVM diameter < 3 cm (P < 0.05). CONCLUSIONS: A series of risk factors were related to intracranial hemorrhage and some of them had considerable influence on prognosis, which, could help to reduce the risk of intracranial hemorrhage and improve long-term survival rate. PMID- 26379899 TI - Zoster duplex: a clinical report and etiologic analysis. AB - OBJECTIVE: Herpes zoster (HZ) duplex is a rare disease presentation. The mechanisms of varicella zoster virus (VZV) reactivation in multiple dermal regions are unknown. To present a HZ duplex case occurring in an immunocompetent woman and to analyze the possible underlying causes of HZ duplex. METHODS: We present a HZ duplex case in an immunocompetent woman and analyzed the possible contributing factors in 36 HZ duplex cases. Continuously distributed variables were categorized by numbers and percentages. RESULTS: In our study, 24 cases (66.7%) were from Asia, 16 cases (44.4%) were in individuals >= 50 years of age, and 17 cases (47.2%) occurred in immunocompromised patients. Of the 36 cases, 23 involved women (63.9%) and 13 involved men. Eighteen patients suffering from HZ duplex, 13 of which were women (72.2%), did not suffer from any chronic systemic disease or have a long history of taking drugs. CONCLUSION: HZ duplex is a rare event that can occur in both immunocompetent and immunosuppressed individuals. HZ duplex might be associated with the Asia region, advanced age, immunosuppression, and being female. PMID- 26379900 TI - Neutrophil-lymphocyte ratio in systemic lupus erythematosus disease: a retrospective study. AB - BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease. Lupus nephritis (LN) is an important cause of morbidity and even mortality in patients with SLE. Some evidences suggest that neutrophil-lymphocyte ratio (NLR) associated with different inflammatory malignancies, ischemic injury and cardiovascular disease. Few scholars have investigated the relationship between NLR and SLE. This study aims to evaluate the role of NLR in SLE without nephritis and LN patients. METHODS: A total of 228 subjects were participated in this study. 79 diagnosed with SLE in patients group and 149 healthy age-and sex matched in control group. In patient team, 20 of them were diagnosed with LN. RESULTS: The SLE without nephritis group showed significantly higher NLR than control group (control=2.00+/-0.76, SLE=4.26+/-3.38, P<0.001), and the NLR values of the patients with LN were higher than those of the patients without LN (SLE=4.26+/-3.38, LN=7.21+/-6.01, P<0.001). Receiver-operating characteristics analysis (ROC) of NLR to predict SLE showed that the area under the curve (AUC) was 0.757. The cutoff value using the ROC curve was 3.13 (sensitivity, 0.574; specificity, 0.926; 95% confidence interval (CI), 0.668-0.845; P<0.001). While ROC analysis of NLR to predict LN showed that the AUC was 0.828). Logistic regression analysis showed that SLE without nephritis and LN were independently related to NLR. CONCLUSION: NLR is independently associated with SLE, and it may be a promising marker that reflects renal involvement in patients with SLE. PMID- 26379901 TI - Comparison of two different circular-stapler techniques for creation of gastrojejunostomy anastomosis in bariatric Roux-en Y gastric bypass. AB - BACKGROUND: Circular-stapled anastomosis with trans-oral anvil insertion is one of the most commonly used methods for the creation of the gastrojejunostomy in laparoscopic Roux-en-Y gastric bypass (LRYGB). We present a retrospective analysis of laparoscopic gastric bypass by comparing 2 techniques of circular stapled gastrojejunostomy; Orvil(TM) and hand-made Orvil. METHODS: Patients who were subjected to LRYGB without any concomitant procedures were observed over a 13-months period at the "Obesity clinic of a University". A total of 94 patients with morbid obesity were subjected to LRYGB. Gastrojejunostomy with circular stapler and Orvil(TM) (CS-O) was performed to 58 patients and 36 patients underwent through the surgery with circular-stapler and hand-made Orvil (CS-HMO). Demographics, clinic, intraoperative data, postoperative complications, and the length of hospital stay were evaluated. RESULTS: Ninety-four patients with mean age of 37.2 years and average body mass index of 58.1 kg/m(2) underwent laparoscopic Roux-en-Y gastric bypass. Laparoscopic surgeries of all patients were successful and major intraoperative complications were not reported. Demographic data and complication rates were similar in both groups. The operative time in group CS-HMO was significantly higher (P=0.03) when compared to group CS-O. There was no anastomotic leak in both groups. CONCLUSION: The use of hand-made Orvil is a technically feasible and safe method for performing the gastrojejunostomy. This technique can be successfully used in case of difficulties for obtaining the Orvil(TM) or reducing the operational costs. PMID- 26379902 TI - Acute pulmonary embolism with electrocardiagraphic changes mimicking acute coronary syndrome: a case report and literature review. AB - Acute pulmonary embolism (PE) is potentially a life threatening emergency that needs prompt management to reduce preventable deaths. Symptoms like dyspnoea and chest discomfort often lack specificity and overlap with acute coronary syndrome (ACS). Importantly, electrocardiographic changes associated with PE are reported to be variable with some ECG patterns mimicking ACS, posing problems in the differential diagnosis. More recently, precordial T wave inversion has been described to be a clue to suggest PE. However, this ECG change is more likely to present in ACS. We herein reported a case of a 78-year-old man presenting with progressive shortness of breath on exertion secondary to submassive pulmonary embolism which was initially misdiagnosed as ACS due to diffuse T wave inversion in both precordial leads V1-6 and inferior Leads II, III and aVF. Here, we discussed the diagnosis of this case and reviewed the medical literature with an emphasis on the limitations of ECG for the differentiation between PE and ACS. PMID- 26379903 TI - Effects of endovenous laser ablation on vascular tissue: molecular genetics approach. AB - BACKGROUND: Endovenous laser ablation (EVLA) is a treatment option for lower extremity varicose veins. In the present study, we investigate to the genetic changes and possibility of living tissue in the saphenous vein wall after the EVLA procedure. METHODS: Eleven saphenous vein grafts were randomized in two groups: (1) 4 cm SVG segments of performed EVLA procedure in study group, (2) 4 cm segments of SVG none performed EVLA procedure in control group. SVG were taken from the remnants of distal saphenous vein grafts prepared for the bypass procedure but not used. SVG was approximately 8 cm in length and was divided into two parts 4 cm in length. One half was exposed to laser energy, while the other half of the same vein graft was untreated as a control. EVLA was performed on complete saphenous veins in the study group. Abnormal genetic changes of the SVG were observed with a Tri-Reagent method and quantified with a NanodropTM spectrophotometer. RESULTS: Histopathological changes indicated that the intima including the endothelium was completely necrotized in the study group. It was observed that intimal thermal-energy-induced injury did not reach the media. Histopathological examination showed that homogenous eosinophilic discoloration and coagulation necrosis characterized the laser related thermal damage as well. CONCLUSIONS: In this preliminary study, we found that living tissue remained in the SVG wall after application of laser ablation, and we also detected abnormal genetic changes in the study group compared with the control group. PMID- 26379904 TI - Neurofibroma and lipoma in association with giant congenital melanocytic nevus coexisting in one nodule: a case report. AB - Giant congenital melanocytic nevi (GCMN) are rare conditions that defined as melanocytic lesion recognized at birth, which will reach a diameter larger than 20 cm, and they occur in about 1 per 500,000 newborns. Despite its rarity, they may associate with severe abnormalities like spina bifida occulta, meningocele, club foot and hypertrophy or atrophy of deeper structures of a limb, Carney complex, premature aging syndromes, neurofibroma, vitiligo, lipoma and dysplasia of bilateral hip impact on the patient. In this case, we report a 3-years-old male child presenting a GCMN with large, blackish, and thick nevus covering over the entire neck, back, and lower to the waist level. We highlight the importance of proper histopathological examination of the biopsy taken from the single huge nodule which revealed features of both neurofibroma and lipoma coexisting. The objective of this paper is to report a rare case with the clinical and pathologic findings. PMID- 26379905 TI - Metabolomics in bladder cancer: a systematic review. AB - Bladder cancer (BC) is the most common urological malignancy. Early diagnosis of BC is crucial to improve patient outcomes. Currently, metabolomics is a potential technique that can be used to detect BC. We reviewed current publications and synthesised the findings on BC and metabolomics, i.e. metabolite upregulation and downregulation. Fourteen metabolites (lactic acid, leucine, valine, phenylalanine, glutamate, histidine, aspartic acid, tyrosine, serine, uracil, hypoxanthine, carnitine, pyruvic acid and citric acid) were identified as potential biomarkers for BC. In conclusion, this systematic review presents new opportunities for the diagnosis of BC. PMID- 26379906 TI - A prospective, proof-of-concept investigation of KPAX002 in chronic fatigue syndrome. AB - Stimulant drugs and various micronutrient interventions have previously been studied in chronic fatigue syndrome (CFS) but they have never been studied in combination. This proof of concept investigation seeks to examine the clinical effects and safety profile of KPAX002 (a combination of methylphenidate hydrochloride and mitochondrial support nutrients) in patients with CFS. Fifteen patients diagnosed with CFS by 1994 Fukuda criteria were recruited and treated with KPAX002 to explore a potential synergistic effect of this combination. Fatigue and concentration disturbance symptoms were measured at baseline, 4 weeks, and 12 weeks using two clinically validated tools: Checklist Individual Strength (CIS) and Visual Analog Scale (VAS). The primary outcome objective was a decrease in the total CIS score of >=25% in at least 50% of the subjects. The mean total CIS score decreased by 36.4 points (34%) at 12 weeks (P<0.0001), corresponding to a >=25% decrease in 87% of the participants. Treatment with KPAX002 was well tolerated and significantly improved fatigue and concentration disturbance symptoms in greater than 50% of patients with CFS. These results were statistically significant. This combination treatment is worthy of additional investigation. PMID- 26379907 TI - Molecular analysis of biofilms on the surface of neonatal endotracheal tubes based on 16S rRNA PCR-DGGE and species-specific PCR. AB - Ventilator-associated pneumonia (VAP) results in considerable morbidity and mortality in neonatal intensive care units. VAP is associated with polymicrobial biofilms that form on endotracheal tubes (ETTs). We aimed to evaluate the diversity and the bacterial community in biofilms on ETTs extubated from mechanically ventilated newborns. ETTs (N = 29) and aerobic sputum cultures were obtained from 20 mechanically ventilated newborns. Denaturing gradient gel electrophoresis (DGGE) was used to characterize the bacterial species in the biofilms on the ETTs. Species-specific PCR was used to detect common oropharyngeal Streptococcus species and known ETT-associated pathogens. DGGE profiling of ETT biofilms showed multiple banding patterns indicating a diverse bacterial community. The dominant bacterial species were Klebsiella spp. (29/29), Streptococcus spp. (27/29), and Pseudomonas spp. (24/29). The most frequently occurring Streptococcus species was Streptococcus mitis (N = 18). Oropharyngeal bacteria were present in 25 of 29 ETT specimens. Streptococcus spp. often co existed with K. pneumoniae and/or P. aeruginosa. In contrast, only one bacterial species was isolated from each sputum culture, K. pneumoniae or Acinetobacter baumannii. Our results demonstrated that Klebsiella spp., Streptococcus spp., and Pseudomonas spp. were the most frequent microbes on the surface of neonatal ETTs. The co-existence of oral commensals and pathogenic bacteria on the same tubes may play a crucial role for biofilm formation. PMID- 26379908 TI - The predictive value of physical examination in the decision of laparotomy in penetrating anterior abdominal stab injury. AB - A selective conservative treatment for penetrating anterior abdominal stab injuries is an increasingly recognized approach. We analyzed patients who followed-up and treated for penetrating anterior abdominal stab injuries. The anterior region was defined as the area between the arcus costa at the top and the mid-axillary lines at the laterals and the inguinal ligaments and symphysis pubis at the bottom. An emergency laparotomy was performed on patients who were hemodynamically unstable or had symptoms of peritonitis or organ evisceration; the remaining patients were followed-up selectively and conservatively. A total of 175 patients with purely anterior abdominal injuries were included in the study. One hundred and sixty-five of the patients (94.29%) were males and 10 (5.71%) were females; the mean age of the cohort was 30.85 years (range: 14-69 years). While 16 patients (9%) were made an emergency laparotomy due to hemodynamic instability, peritonitis or evisceration, the remaining patients were hospitalized for observation. During the selective conservative follow-up, an early laparotomy was performed in 20 patients (12%), and a late laparotomy was performed in 13 patients (7%); the remaining 126 patients (72%) were discharged after non-operative follow-up. A laparotomy was performed on 49 patients (28%); the laparotomy was therapeutic for 42 patients (86%), non-therapeutic for 4 patients (8%), and negative for 3 patients (6%). A selective conservative approach based on physical examination and clinical follow-up in penetrating anterior abdominal stab injuries is an effective treatment approach. PMID- 26379909 TI - Image classification of liver cancer surrounding right hepatic pedicle and its guide to precise liver resection. AB - PURPOSE: The aim of this study was to explore the feasibility of image classification of liver cancer surrounding right hepatic pedicle (RHP) and its guide to precise liver resection. METHODS: Twenty-five patients with single liver cancer surrounding RHP were collected. According to the adjacent relationship between neoplasm and RHP shown in CT or MRI, the liver neoplasms were divided into the 4 types, type A neoplasm infiltrating or surrounding RHP, type B neoplasm locating in the anterior side of RHP, type C neoplasm locating in the dorsal side of RHP and type D neoplasm locating between the two branches. On the basis of image classification, operation project including hepatic vascular occlusion (HVO) and surgical resection procedure was designed. In the end, preoperative classification and surgical design was compared with operative results. RESULTS: The locations of liver neoplasms were completely in line with preoperative classification. The methods of HVO and range of surgical resection were essentially coincident with preoperative plan. Pringle maneuver, total hepatic and hemihepatic vascular occlusion were applied. Four patients with type A neoplasms underwent right hemihepatectomy or extended right hepatectomy. Seven with type B received right anterior lobectomy or mesohepatectomy. Six with type C underwent segment V, VI resection, and eight with type D received right anterior or posterior lobectomy. All operations were smoothly finished. CONCLUSION: Preoperative classification guided by RHP can provide the accurate location information for liver cancer surrounding RHP, contribute to choosing suitable method of HVO and reasonable range of hepatic resection for precise surgery. PMID- 26379910 TI - p53 mediated apoptosis in osteosarcoma MG-63 cells by inhibition of FANCD2 gene expression. AB - PURPOSE: The aim of this study was to investigate the association between osteosarcoma (OS) and Fanconi anemia (FA) related pathways and the molecular mechanisms. METHODS: siRNA for Fanconi anemia complementation group D2 (FANCD2) was constructed and transfected into the osteosarcoma cell line MG-63 cells. Expression of TP53INP1, p53, p21, caspase-9, and caspase-3 mRNA in MG-63 cells were examined by real-time fluorescence quantitative PCR, and the protein levels were also determined by western blot. RESULTS: After silence of the FANCD2 gene in MG-63 cells, cell proliferation was inhibited, cell cycle was arrested and cell apoptosis was induced. The apoptosis was mediated by the p53 signaling pathway. After FANCD2 expression was inhibited, TP53INP1 gene expression was up regulated, phosphorylation of p53 was promoted and the p21 protein was activated, leading to cell cycle arrested in G1, finally resulted in caspase-dependent cell apoptosis. CONCLUSIONS: Inhibition of FANCD2 gene expression can induce apoptosis of osteosarcoma cells, which indicated that FANCD2 played an important role in the development of osteosarcoma and it might be a potential target for treatment of osteosarcoma. PMID- 26379911 TI - Clinical, pathological and sonographic characteristics of unexpected gallbladder carcinoma. AB - OBJECTIVES: To investigate the clinical, pathological, and sonographic characteristics of unexpected gallbladder carcinoma (UGC). METHODS: Of 5424 patients who had undergone cholecystectomy from December 2006 to October 2013, 54 patients with primary gallbladder carcinomas confirmed by pathological diagnosis were identified. The patients were divided into two groups: diagnosed before operation (n=34) and UGC groups (n=20), of whom the clinical, pathological, and sonographic characteristics were compared. RESULTS: No significant differences in age, gender, location of lesion, histological type, length of the gallbladder, existence of biliary sludge, and intestinal gas interference between the two groups were found (all P>0.05). The clinical symptoms, laboratory abnormalities, tumor markers, coexisting gallbladder stones, lesion size, lesion type, degree of differentiation, and tumor staging showed statistically significant differences between the two groups (all P<0.05). On ultrasound, the width of the gallbladder, gallbladder wall thickness, vascularity on color Doppler ultrasound, and bile volume in the gallbladder showed significant differences (all P<0.05). CONCLUSIONS: UGCs are commonly found at an early stage, often well differentiated, wall thickened, and are generally accompanied with cholelithiasis. UGCs should be taken into consideration in cases with cholelithiasis or small gallbladder on ultrasound. PMID- 26379912 TI - Alcohol dehydrogenase 1C (ADH1C) gene polymorphism and alcoholic liver cirrhosis risk: a meta analysis. AB - The association between alcohol dehydrogenase 1C (ADH1C) gene polymorphism and alcoholic liver cirrhosis (ALC) has been analyzed in several studies, but results have been conflicting. In this study, a meta-analysis was performed to assess the associations between the ADH1C polymorphism and risk of ALC. Relevant studies were identified using PubMed, Web of Science, CNKI and Wanfang databases up to January 10, 2015. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association using the fixed or random effect model. A total of 16 case-control studies, including 1375 cases and 1802 controls, were included. Overall, no significant association between the ADH1C polymorphism and ALC risk was found (dominant model: OR=0.87, 95% CI: 0.62-1.23; recessive model: OR=1.30, 95% CI: 0.84-1.99; *1/*2 vs. *1/*1: OR=0.87, 95% CI: 0.63-1.21; *2/*2 vs. *1/*1: OR=1.10, 95% CI: 0.71-1.70). In the subgroup analysis by ethnicity, we observed a significant association in Asian descent (*1/*2 vs. *1/*1: OR=1.63, 95% CI: 1.07-2.49), while a decreased risk was found among Caucasians (dominant model: OR=0.81, 95% CI: 0.66-0.99; *1/*2 vs. *1/*1: OR=0.76, 95% CI: 0.61-0.95). This meta-analysis demonstrated that the ADH1C polymorphism might increase the risk of ALC in Asians, while it may be a protective factor for ALC among Caucasians. PMID- 26379913 TI - Correlation of bone fragments reposition and related parameters in thoracolumbar burst fractures patients. AB - The aim of this study is to determine if thoracolumbar vertebral body collapse or canal compromise (CC) is associated with reposition of bone fragment. We retrospective review medical charts of patients with thoracolumbar burst fractures from July 2010 to September 2013. The fractures were classified according to the Arbeit Fuer Osteoosynthese (AO) classification system. Neurological status was classified according to American Spinal Injury Association (ASIA). Patients were divided into two groups (reposition group and non-reposition group) according to whether the bone fragments were reposition or non-reposition after surgery. Mimics measured mid-sagittal canal diameter (MSD), transverse canal diameter (TCD), local kyphosis (LK) and calculated anterior vertebral body compression ratio (AVBCR), middle vertebral body compression ratio (MVBCR), posterior vertebral body compression ratio (PVBCR), and mid-sagittal canal diameter compression ratio (MSDCR) on the preoperative CT image. The results indicated that 55 patients were included in the study. There are 35 patients with reposition of bone fragment and 20 patients with non-reposition of bone fragment after surgery. There were significant difference on MSD (t = 3.258, P = 0.002), TCD (t = 2.197, P = 0.032), AVBCR (t = -2.063, P = 0.044), MVBCR (t = -2.526, P = 0.015), PVBCR (t = -2.211, P = 0.031), MSDCR (t = -4.975, P = 0.000) between two groups before surgery. There was a significant correlation between reposition of bone fragment and AO classification (OR = 5.251, P = 0.022), and MSDCR (OR = 7.366, P = 0.007). There was no significant correlation between reposition and AVBCR, MVBCR, PVBCR, LK, MSD and TCD. In conclusion, this study indicates that AO classification and MSDCR are predictors of reposition of bone fragment. PMID- 26379914 TI - Genetic risk of lung cancer associated with a single nucleotide polymorphism from EXO1: a meta analysis. AB - BACKGROUND/AIM: Several reports have investigated the role of exonuclease 1 (EXO1) rs1047840 in lung cancer risk in different ethnic populations. Nevertheless, the results have been controversial. We aimed to assess the possible association between EXO1 rs1047840 and risk of lung cancer in a meta analysis. METHODS: Human hospital- or population-based studies released before December 16, 2013 were identified by systematic search of the PubMed and Embase databases. Data were extracted in duplicate from each study. An OR and 95% CI (odds ratio and 95% confidence interval) was calculated to evaluate the effects of EXO1 rs1047840 on lung carcinogenesis. RESULTS: A total of 1,114 lung cancer patients and 1,166 well-matched controls were analyzed in this study. The fixed effects meta-analysis revealed that carriage of a single A allele, compared to the carriage of single G allele, was associated with 1.18 times increased risk of lung cancer (A vs. G: OR =1.18; 95% CI: 1.03-1.35; PHeterogeneity, 0.121). CONCLUSION: This first meta-analysis demonstrates that the A allele of EXO1 rs1047840 may confer modulating effects on the risk of lung cancer and could be used as a marker for early detection and primary prevention. PMID- 26379915 TI - Analysis of different fractionations of three-dimensional conformable radiotherapy for esophageal cancer. AB - This study aims to observe and discuss the curative and side effects of three different fractionation regimen of three-dimensional conformable radiotherapy (3DCRT) for esophageal cancer. A total of 169 untreated patients of esophageal cancer were randomized into three groups: groups A (conventional group, 2.0 Gy per time), B (2.5 Gy group, 2 Gy per time), and C (3.0 Gy group, 3.0 Gy per time), respectively. Groups A, B, and C are similar in terms of partial response (P = 0.35). However, the three groups had no significant differences in terms of the complete response (P = 0.63). The three-year survival rate of group B was higher than those of the other two groups, and the difference was significant (P = 0.047). For the three-year local control rate, that of group B was also higher than those of groups A and C, but the difference was not significant (P = 0.067). The incidence rate of 3 level esophagitis and bronchitis was highest in group C (P = 0.023 and P = 0.064). The 3 level tardive radioactive esophagitis in group C was higher than those in other two groups (P = 0.037 and P = 0.04). The incidence rate of the 3 level advanced lung reaction was also the highest in the three groups (P = 0.041). The effect is better and the side effect is tolerable for the 2.5 Gy per fraction, 5 times per week; thus, it can be used clinically for 3DCRT for esophageal carcinoma. PMID- 26379916 TI - The role of FDG PET/CT in evaluation of mediastinal masses and neurogenic tumors of chest wall. AB - We evaluated the efficiency of FDG PET/CT for the differentiation of malignant from benign mediastinal masses and neurogenic tumors of chest-wall. METHODS: The 88 patients with chest wall-mediastinal masses who underwent examination before operation were retrospectively reviewed. Size, CT density (HU mean) and SUVmax of mediastinal and chest wall lesions were determined. Statistical differences of these parameters were compared between groups by Mann-Whitney U test. Receiver operating characteristic curve (ROC) analysis with respect to SUVmax was performed to determine the best cutoff value for differentiating benign from malignant masses. RESULTS: The overall sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of PET/CT in detection of malignancy were 90%, 55.17%, 67%, 50.94% and 91.43%, respectively. The SUVmax, HU mean and size were higher in malignant cases (P < 0.05). To distinguish benign and malignant lesions, the cut off value of SUVmax was 4.67. The lesion SUVmax was significantly associated with the lesion size and lesion HU mean values (P < 0.05). The value of SUVmax and HU mean were higher in solid benign lesions than those of cystic benign lesions (P < 0.05). The lesion size was higher in cystic lesions (P = 0.000). The mean SUVmax was significantly higher in invasive thymomas than those of non-invasive forms (P = 0.029). CONCLUSION: FDG PET/CT may be complementary to conventional imaging methods for the evaluation of mediastinal and chest wall masses. PET/CT may reduce unnecessary invasive investigations for diagnosis in patients with nonavid or low avid FDG lesions. However confirmatory tissue sampling is required to confirm PET positive findings for the definite diagnosis. PMID- 26379917 TI - Using suture and locking anatomical bridging plate to fix comminuted mid-shaft clavicle fractures with intramedullary nail assistance in reduction. AB - BACKGROUND: During conventional plate fixation of comminuted midshaft fracture of the clavicle, wedge-shaped fragments often need to be fixed with lag screws. A new procedure, which included intramedullary K-wire assistance in reduction, binding fragments by suture, and eventually bridging plate fixation, was compared with conventional techniques. HYPOTHESIS: This new procedure is more effective than the conventional techniques, and the fixation of free fragments using lag screws is not necessary. MATERIAL AND METHODS: This was a retrospective study of 60 patients from August 2008 to March 2013 with comminuted midshaft clavicular fractures with wedge-shaped fragments. Seventeen patients were treated with conventional plate fixation, and the wedge-shaped fragments were fixed using lag screws (LSPF). Another 43 patients were treated with the new procedure, including intramedullary K-wire assistance in reduction, binding of wedge-shaped fragments by suture, and bridging plate fixation (KSB). Patients were followed for an average of 13 months and radiographs were used to observe fracture healing. Shoulder function was assessed using the Constant Score System (CSS). RESULTS: There was no significant difference in bone healing time and shoulder function between the two study groups. The operating time for KSB was significantly shorter than conventional LSPF (P=0.014). Fractures healed in 14.9+/-5.59 weeks for the conventional LSPF group and in 13.6+/-3.59 weeks for the KSB group. One patient treated with conventional LSPF had implant failure and underwent a second operation. CONCLUSIONS: KSB is a simple and effective procedure for comminuted midshaft clavicular fractures. The wedge-shaped fragments in comminuted midshaft clavicular fractures do not always need to be fixed by lag screws and the new procedure described is an effective treatment alternative. LEVEL OF EVIDENCE: Level IV. PMID- 26379918 TI - Gender dependent association of 25-hydroxyvitamin D and circulating leptin in saudi subjects: influence of dyslipidemia. AB - BACKGROUND AND OBJECTIVE: Leptin and vitamin D play an important role in obesity development and metabolic effects; however, the association between leptin and vitamin D is not well studied in Saudi subjects. We aimed to examine gender dependent association between serum leptin and 25-OH-VitD in adult Saudi subjects. SUBJECTS AND METHODS: For this cross-sectional study in a cohort of 259 Saudi adults (100 male, age: 46.4 +/- 0.9 yr [mean +/- SD]; BMI: 27.8 +/- 0.5 Kg/m(2)) and (159 female, age 46.5 +/- 0.7 [mean +/- SD]; BMI: 28.4 +/- 0.4 Kg/m(2)) anthropometrics, fasting bloods, and biochemical data were collected. Serum leptin and 25-hydroxyvitamin D (vitamin D or 25-OH-VitD) were quantified using an enzyme-linked immunosorbent assay. RESULTS: Circulating leptin and vitamin D levels were significantly higher in females compared to male (P<0.001 and P<0.01 respectively). Visceral adiposity index (VAI), triglycerides and total cholesterol were significantly higher (P<0.05, P<0.001, and P<0.05, respectively) while HDL-cholesterol were lower (P<0.001) in male compared to female subjects. In males, vitamin D levels were positively associated with leptin (r = 0.196, P<0.05). CONCLUSION: Vitamin D was positively associated with serum leptin in male Saudi subjects. Additionally, male subjects were found to be dyslipidemic, which might be a responsible factor for this discordant association between vitamin D and leptin in Saudi population. PMID- 26379919 TI - Pharmacogenetic association between XRCC1 polymorphisms and improved outcomes in bladder cancer patients following intravesical instillation of epirubicin. AB - BACKGROUND: XRCC1 is a multi-domain protein associated with bladder cancer. We investigated the relationship between the distribution of XRCC1 polymorphisms (rs915927 and rs2854501) and clinical outcomes following intravesical instillation with epirubicin (EPI) or mitomycin C (MMC). METHODS: A TaqMan assay was performed to determine genotypes of 240 individuals diagnosed with bladder cancer. Logistic regression was used to assess the association between polymorphisms and relapse-free survival (RFS) of patients. Quantitative real-time polymerase chain reaction was performed to determine expression of XRCC1 polymorphisms. Survival curves were generated using the Kaplan-Meier method. RESULTS: Risk of bladder cancer recurrence was significantly reduced in patients receiving EPI who had higher incidences of XRCC1 polymorphisms (P=0.009 for rs915927, P=0.001 for rs2854501). In participants administered MMC, results were not statistically significant. CONCLUSIONS: Polymorphisms in XRCC1 SNP variants (rs915927 and rs2854501) were associated with improved clinical outcomes following EPI treatment. PMID- 26379920 TI - Association between plasma homocysteine and progression of early nephropathy in type 2 diabetic patients. AB - There is now growing evidence supporting the association between renal insufficiency and accumulation of plasma homocysteine (Hcy). However, the role of Hcy in the development of diabetic nephropathy (DN) in type 2 diabetic patients is not clearly elucidated. To this end, we performed a prospective observational study in 208 patients and 49 controls. We show that baseline level of Hcy is significantly enhanced in patients with DN and is associated with the severity of the disease. Focusing on patients at early DN stage (n = 157), after four-year follow-up, we find that increase in plasma Hcy level correlates with greater renal failure characterized by faster decline in estimated glomerular filtration rate (eGFR). Using a multivariate linear regression model, we show that plasma Hcy remains significantly associated with eGFR decline after controlling for other progression promoters. Our results support that plasma Hcy is an independent risk factor as well as an early predictor for DN progression in type 2 diabetic patients. PMID- 26379921 TI - Effects of ketamine exposure on dopamine concentrations and dopamine type 2 receptor mRNA expression in rat brain tissue. AB - OBJECTIVE: To explore the effects of ketamine abuse on the concentration of dopamine (DA), a monoamine neurotransmitter, and the mRNA expression of dopamine type 2 (D2) receptors in brain tissue, we used male Wistar rats to model ketamine abuse through chronic intraperitoneal infusion of ketamine across different doses. METHODS: The rats were sacrificed 45 minutes and 1, 2, and 3 weeks after initiating the administration of ketamine or normal saline, as well as 3 days following discontinuation. Brain tissue was harvested to examine the concentration of 2,5-dihydroxyphenylacetic acid and homovanillic acid, the primary metabolites of DA, as well as the expression of D2 receptor mRNA. In addition, behavioral changes were observed within 30 minutes of administration, and withdrawal symptoms were also documented. A factorial experimental design was used to investigate variations and correlations in the primary outcome measures across the four doses and five time points. Brain DA concentrations were significantly higher in the ketamine-treated groups compared with the saline treated group, with 30 mg/kg > 10 mg/kg > 60 mg/kg > saline (P < 0.05). The D2 receptor mRNA expression exhibited an inverse downregulation pattern, with 30 mg/kg < 10 mg/kg < 60 mg/kg < saline (P < 0.05). In the 10 mg/kg and 30 mg/kg ketamine-treated groups, the DA concentration and D2 receptor mRNA level in the brain tissue correlated with the dose of ketamine (r = 0.752, r = -0.806), but no significant correlation was found in the 60 mg/kg group. RESULT: These findings indicated that chronic dosing with ketamine increased the concentration of DA in rat brain tissue by increasing DA release or interrupting DA degradation. D2 receptor mRNA expression likely decreased because of stimulation with excessive DA. CONCLUSION: High-dose (60 mg/kg) ketamine had potent paralyzing effects on the central nervous system of rats and weakened the excitatory effects of the limbic system. Brain DA and D2 receptor mRNA may be associated with ketamine abuse. PMID- 26379922 TI - Application of total parathyroidectomy with auto-transplantation for uremia secondary hyperparathyroidism treatment. AB - BACKGROUND: Secondary hyperparathyroidism (sHPT) is a common acquired disorder in patients with chronic renal failure. Despite the development of new therapeutic agents, a majority of patients will require parathyroidectomy. The aim of this study was to evaluate total parathyroidectomy with auto-transplantation of trace amounts of parathyroid tissue as a surgical option in uremia sHPT treatment. METHODS: Clinical data of 50 sHPT patients who underwent total parathyroidectomy with auto-transplantation between January 2011 and December 2013 were reviewed retrospectively. Symptoms such as bone pain and fractures, concentrations of intact parathyroid hormone (iPTH), levels of ionized calcium and serum phosphorus, and activity of alkaline phosphatase were recorded before and after parathyroidectomy. RESULTS: After operation, signs of pruritus, bone pain and muscle weakness was disappeared, iPTH level and serum phosphate concentration were declined markedly. No serious postoperative complications were observed. Follow-up observation was around 28 months. One female patient (2%) died 3 months after surgery due to heart failure, and another patient (2%) had persistent disease. All other patients recovered during the follow-up period. CONCLUSIONS: Total parathyroidectomy with auto-transplantation of trace amounts of parathyroid tissue was considered to be a feasible, safe and effective surgical option for the treatment of sHPT. PMID- 26379923 TI - Over-expression of miR-675 in formalin-fixed paraffin-embedded (FFPE) tissues of breast cancer patients. AB - BACKGROUND: Dysregulation of miR-675 has been found in a variety of solid tumors. MiR-675 has been suggested as having both oncogenic and tumor suppression properties in cancer. However, there is no evidence whether miR-675 is involved in breast cancer. The objective of this study was to evaluate the expression status of miR-675 and its clinical relevance in breast cancer patients. METHODS: The expression level of miR-675 was detected in 100 breast cancer patients and 38 cancer-free controls using real-time quantitative PCR. The clinicopathological characteristics of miR-675 in breast cancer were also investigated. All statistical analyses were performed using SPSS 20.0. RESULTS: The study showed that miR-675 was significantly up-regulated in breast cancer patients compared with controls (P < 0.01). There was no significant difference in age, lymph nodes stage, ER status and PR status between patients with and without miR-675 over expression (P > 0.05). The frequency of miR-675 over-expression was higher in the patients of histological grade I-II than in others (50% versus 9%, P = 0.011). The expression level of miR-675 had a high correlation with miR-24/93/98/378 in breast cancer patients. CONCLUSIONS: Taken together, our study demonstrated that miR-675 in formalin-fixed paraffin-embedded (FFPE) tissues might serve as a good source for biomarker discovery and breast cancer validation. PMID- 26379924 TI - Analgesic effect of TAK-242 on neuropathic pain in rats. AB - BACKGROUND: The current study investigated the analgesic effect of the Toll-like receptor 4 (TLR4) specific antagonist TAK-242 on neuropathic pain in rats and its underlying mechanism. METHODS: A total of 132 adult Sprague-Dawley (SD) rats were randomly divided into four groups: the sham operation group, the neuropathic pain model group, the TAK-242 low-dose treatment group, and the TAK-242 high-dose treatment group. The heat pain and mechanic pain thresholds of rats were detected on preoperative day 1 and postoperative days 1, 3, 7, and 10. The expression levels of IkappaBalpha, p65, IL-1beta, and TNF-alpha in the spinal cord dorsal horn were detected on postoperative day 7 in one group of rats. RESULTS: Compared with rats in the sham operation group, the heat pain and mechanic pain thresholds of the rats in the neuropathic pain model group significantly decreased; their expression levels of p65, IL-1beta, and TNF-alpha significantly increased; and their expression level of IkBalpha significantly decreased. Compared with the neuropathic pain group, high doses of TAK-242 significantly inhibited the expression of p65, IL-1beta, and TNF-alpha; significantly increased the expression level of IkBalpha; and upregulated the heat pain and mechanic pain thresholds. CONCLUSION: TAK-242 might improve neuropathic pain through downregulation of the NF-kappaB pathway. PMID- 26379925 TI - Description of intraoral pressures on sub-palatal space in young adult patients with normal occlusion. AB - Under normal conditions, the oral cavity presents a perfect system of equilibrium between teeth, soft tissues and tongue. The equilibrium of soft tissues forms a closed capsular matrix, generating differences with the atmospheric environment. This difference is known as intraoral pressure. Negative intraoral pressure is fundamental to the stabilization of the soft palate and tongue, reducing neuromuscular activity for the permeability of the respiratory tract. Thus, the aim of this study was to describe the variations of intraoral pressure of the sub palatal space (SPS) under different physiological conditions and biofunctional phases. A case series was conducted with 20 individuals aged between 18 and 25. The intraoral pressures were measured through a system of cannulae connected to a digital pressure meter in the SPS during seven biofunctional phases. Descriptive statistics were used based on the mean and standard deviation. The data recorded pressure variations under physiological conditions, reaching 65 mbar as the intraoral peak in forced inspiration. In the swallowing phase, peaks reached 91.9 mbar. No pressure variations were recorded in terms of atmospheric changes with the mouth open and semi-open. The data obtained during the swallowing and forced inspiration phases indicated forced lingual activity. In the swallowing phase, the adequate position of the tongue creates negative intraoral pressure, which represents a fundamental mechanism for the physical stabilization of the soft palate. This information could contribute to subsequent research into the treatment of primary roncopathies. PMID- 26379926 TI - The "temporary caging" technique for catheter navigation in patients with intracranial wide-necked aneurysms. AB - Endovascular treatment of wide-necked aneurysms with preservation of the parent artery remains a challenge. The authors describe a novel and simple technique to navigate a balloon or stent-delivery catheter across a wide-necked aneurysm in which previously existing methods could have failed to pass the catheter across the neck of the aneurysm, which we have named "temporary caging" technique. The technical results using this method are presented in 6 cases. PMID- 26379927 TI - Age-related changes of normal prostate: evaluation by MR diffusion tensor imaging. AB - In this study, fifty healthy normal volunteers were divided into 3 groups according to age: group A (15-30 years, n=14), group B (31-50 years, n=24), group C (>51 years, n=12). The FA and ADC values in PZ and CZ were measured, and difference between the PZ and CZ were assessed. The results indicated that no significant difference were found in the FA and ADC values between the left and right of PZ (P>0.05), but significant differences were observed in the FA and ADC values between PZ and CZ within each group (P<0.05). The FA values of PZ in three groups were 0.227+/-0.052, 0.202+/-0.055, and 0.145+/-0.034, respectively. The ADC values were found to be 1.439+/-0.160*10(-3), 1.652+/-0.256*10(-3), and 2.001+/-0.266*10(-3) mm(2)/s, accordingly. The FA and ADC values in PZ were significantly (P<0.05) different between groups. The FA values of CZ in different groups were found to be 0.291+/-0.083, 0.287+/-0.045, and 0.257+/-0.059, respectively; while the corresponding ADC values were 1.374+/-0.171*10(-3), 1.382+/-0.178*10(-3), and 1.415+/-0.136*10(-3) mm(2)/s, respectively. The FA and ADC values in CZ were not statistically (P>0.05) different between groups. Pearson correlation analysis results showedthat the FA values in PZ havenegative correlation with age (r=-0.498, P<0.05), while the ADC values exhibited a positive correlation with age (r=0.682, P<0.05). No correlations between the changes of FA and ADC values and age were noted in CZ. In conclusion, the FA and ADC values in the normal prostatic PZ were age-dependent. FA decreases and ADC increases with age. In contrast, the FA and ADC values in the normal prostatic CZ were not significantly age-related. PMID- 26379928 TI - Prothrombin C20209T mutation in deep vein thrombosis: a case report. AB - Thrombophilias is a recognized risk factor for thrombotic events. The prothrombin variant G20210A gene mutation has been commonly examined using polymerase chain reaction (PCR). Currently, in many clinical laboratories, performing the PCR in real-time technique, which, in addition to identifying the G20210A mutation, makes possible the detection of other mutations in the 3'UTR of the prothrombin gene by melting curve analysis, due to the ability of this analysis to be amplicon-dependent (e.g., C20209T, C20221T and A20218G). We report the first case in Chile that describes the atypical prothrombin C20209T mutation, in a 50-year old male patient diagnosed with deep vein thrombosis in the lower limb and family history of thrombophilia. In the literature, there are few studies of the prevalence and functionality of this mutation; its association with thrombotic events is controversial. PMID- 26379929 TI - LMNA gene single nucleotide polymorphisms in dilated cardiomyopathy of Han children. AB - OBJECTIVE: To investigate whether LMNA gene mutation is associated with dilated cardiomyopathy (DCM) in Chinese Han Race children. METHODS: DNA was isolated from 78 patients with DCM and 100 healthy Chinese children who served as controls. 12 exons in the functional regions and the adjacent part of introns of the LMNA gene were amplified with polymerase chain reactions (PCR) and the PCR products were sequenced with DNA sequencer. We compared the DNA sequence with Blast software online PubMed website. The differences of allele and genotype between the groups were detected by chi(2) test. RESULTS: No disease-causing mutation in LMNA gene was found in all DCM patients. Three nonsense single nucleotide polymorphisms (SNPs) were identified. 1 The first is c.1908C>T (H566H, rs4641) which was located at exon 10 of LMNA gene. It was found in 29 DCM cases and 15 control subjects. Compared to healthy controls, the frequency of TT and TC genotypes, and the C allele were significantly increased in DCM patients (P<0.05). 2 The second was c.861C>T (A287A, rs5380) which was located at exon 5 of LMNA gene. It was found in 9 DCM cases and 2 control subjects. The frequency of TC genotype was significantly increased in DCM patients (P<0.05). 3 The third was c.1338C>T (D446D, rs5058) which located at exon 7 of LMNA gene. It was found in 8 DCM cases and 3 control subjects. The frequency of TC genotype was significantly increased in DCM patients (P<0.05). CONCLUSION: The SNP of LMNA gene may be associated with the susceptivity of DCM in Chinese Han children. PMID- 26379930 TI - Association between polymorphism of CD20 gene and chronic lymphocytic leukemia in Chinese population. AB - Rituximab was widely used in clinical practice. Some chronic lymphocytic leukemia (CLL) patients were primary or secondary resistance to rituximab, but the mechanism has not been yet clear. CD20 gene coding region was amplified by PCR in 92 cases of newly diagnosed CLL patients and 200 healthy donors. The expression of CD20 was conducted in peripheral blood specimens of CLL patients. Proportions of CD20 expression and fluorescence intensity were detected by flow cytometry. Exon-3 c.246C>T (rs17155019) and Exon-4 c.632C>T (rs2070770) were present in 4.35% (4/92) and 9.78% (9/92) of newly diagnosed CLL patients. The mutations were not found in remaining exons. The frequency of C/C genotype and C allele of rs2070770 were significantly higher than the normal control population (90.22% vs 81.00%, P=0.04; 95.11% vs 90%, P=0.04). There was no significant relationship between genotypes with CLL development (P>0.05), however, C allele of rs2070770 may be associated with CLL (P=0.04, OR=0.46, 95% CI=0.22-0.98). The expression CD20 mRNA, proportion and intensity of CD20 were no significant different between genotypes of two polymorphic loci (P>0.05). Low expression of CD20 for CLL was not associated with mutation of CD20 gene coding region. Other mechanisms, such as promoter methylation, may result in low expression of CD20. PMID- 26379931 TI - In-hospital clinical outcomes of elderly patients (>=60 years) undergoing primary percutaneous coronary intervention. AB - Elderly patients are at high risk of mortality when they present with ST elevation myocardial infarction (STEMI). However, the clinical outcomes of this sub-group undergoing primary percutaneous coronary intervention (PPCI) have not been well established, despite recent advances in both devices and techniques. In the present retrospective cohort study from a Chinese single center, we assessed the clinical outcomes and predictors of mortality in elderly patients (>=60 years) underwent with PPCI. The primary endpoints were immediate angiographic success and in-hospital procedural success. The secondary endpoints were all cause death in hospital. Between January 2011 and December 2013, a total of 184 consecutive patients with acute STEMI underwent PPCI were enrolled. 116 (63.04%) patients were in the elderly group. Despite the difference in lesion complexity between groups, the immediate angiographic success rate was similar (93.97% in the elderly group, and 94.12% in the non-elderly group, P=0.966). The procedural success rate were not significantly different between the two groups (90.52% in the elderly group, and 94.12% in the non-elderly group, P=0.389). However, in hospital mortality was statistically higher in elderly group than in the non elderly group (8.62% Vs 1.47%, P=0.048). The major causes of death were cardiac shock and malignant arrhythmias (ventricular tachycardia and fibrillation). Our results indicate that PPCI in the elderly is feasible and has a high likelihood of immediate angiographic and procedural success. PMID- 26379932 TI - Risk factors of infectious complications following flexible ureteroscope with a holmium laser: a retrospective study. AB - PURPOSE: We aimed to evaluate the effectiveness of flexible ureteroscope for treating kidney stones and the risk factors for infectious complications following flexible ureteroscope (FURS) with a holmium laser. METHODS: We retrospectively reviewed the data of 227 patients with kidney stones who underwent flexible ureteroscope with a holmium laser at our hospital from January 2012 to September 2014, including gender, age, comorbidity, urine analysis results, urine culture results, blood test results, stone size, operative duration, and residual stones. Patients with and without infectious complications were assigned to groups A and B, respectively. The dependent variables were postoperative infectious complications, and the risk factors for infectious complications following FURS were assessed using Chi-square tests and multivariate logistic regression analyses. RESULTS: All the surgeries were successfully completed. The total stone-free rate was 81.9% (n = 186), and the incidence of infectious complications after FURS was 8.37% (n = 19). Fifteen patients (6.61%) developed fever postoperatively, 10 patients (4.41%) developed systemic inflammatory response syndrome (SIRS), 6 patients with fever were considered to have SIRS (2.64%), and 2 patients had sepsis (0.88%). Univariate analyses of groups A and B indicated that pyuria, stone size, operative duration, and infectious stones were risk factors for infectious complications after FURS (P < 0.05). Multivariate logistic regression analyses indicated that pyuria (P = 0.017), operative duration (P = 0.026), and infectious stones (P = 0.030) were independently related to infectious complications. CONCLUSION: Pyuria, operative duration, and infectious stones were risk factors for infectious complications following FURS. Hence, routine urinalysis findings should be carefully considered, particularly the finding of pyuria. PMID- 26379933 TI - Correlation of leptin and soluble leptin receptor levels with anthropometric parameters in mother-newborn pairs. AB - The aim of this study was to investigate if anthropometric parameters are associated with both leptin and soluble leptin receptor (sLEPR) levels in newborns and their mothers. This cross-sectional study was performed in 118 mother-newborn pairs. The venous blood sample of mothers was taken before delivery and immediately after delivery an umbilical cord blood sample was collected. Levels of leptin and sLEPR in maternal and umbilical cord sera were assessed by ELISA. Maternal serum concentration of leptin and sLEPR (6.2 and 25.7 ng/ml, respectively) were higher than in umbilical cord blood (2.4 and 14.2 ng/ml, respectively). However, the newborns and their mothers had higher sLEPR levels than leptin levels. In mothers was observed that leptin levels increase with weight gain in pregnancy and decreased sLEPR levels. Cord leptin levels correlated with neonatal birth weight and length, the body circumferences, placental weight and maternal leptin levels. Cord sLEPR levels correlated with maternal sLEPR and leptin levels. Maternal serum concentration of leptin correlated with pre-pregnancy BMI, weight gain, cord sLEPR and leptin levels. Maternal sLEPR concentration correlated with cord sLEPR levels. The leptin and sLEPR levels in mother-newborn pairs are related with anthropometric parameters and an inverse correlation between leptin levels and sLEPR was observed in pairs. PMID- 26379934 TI - Therapeutic efficacy of Cernilton in benign prostatic hyperplasia patients with histological prostatitis after transurethral resection of the prostate. AB - OBJECTIVE: This study was to prospectively evaluate the therapeutic efficacy of Cernilton in benign prostatic hyperplasia (BPH) patients with histological prostatitis after transurethral resection of the prostate (TURP). MATERIALS AND METHODS: One hundred patients with histological prostatitis were recruited from January 2007 to January 2013. All patients were divided into groups A (mild), B (moderate), and C (severe) based on symptom severity, and then randomly subgrouped into Cernilton group and control group. Patients in Cernilton group were treated with Cernilton for 3 months after TURP, while patients in control group received placebo. A series of patient indicators were evaluated before, perioperatively (peri), and after TURP. RESULTS: The assessed indicators remained unchanged peri-TURP as compared to those before surgery. 6 months after TURP, indicators remained stable in group A, and significant differences were observed in the International Index of Erectile Function-5 (IIEF-5) in group B and in the storage symptom score (Ss), quality of life (QoL) and IEFF-5 in group C. In addition, there were significant differences in Ss, QoL and IEFF-5 between Cernilton group and control group. CONCLUSION: In BPH patients with histological prostatitis after TURP, Cernilton can improve the lower urinary tract symptoms and sexual dysfunction depending on the grade of prostatitis. PMID- 26379935 TI - Pyrosequencing analysis for mutations in embB codon306 among clinical mycobacterium tuberculosis isolates from Qingdao, China. AB - In this study, our objectives was to analyze the molecular characteristics of mutation at embB codon306 in Mycobacterium tuberculosis in Qingdao by pyrosequencing technology, and to assess the value of embB codon306 used as a molecular marker to diagnose multidrug resistant (MDR) TB strains. Pyrosequencing was used to detect mutations at embB codon306 among M. tuberculosis isolates from tuberculosis (TB) patients in Qingdao. The correlation between embB306 mutation and MDR phenotype was evaluated by comparing with conventional drug susceptibility testing results. 60.9% of MDR strains and 15.2% of non-MDR strains carried embB306 mutation, respectively. The percentage of MDR-TB harboring embB306 mutation was significantly higher than that of non- MDR-TB (chi(2)=15.09, P < 0.01). EmbB306 mutation serving as a marker to diagnose MDR-TB comparing with the traditional susceptibility test, the specificity, sensitivity and accuracy were 85%, 61%, and 77%, respectively. EmbB306 mutation is the main mechanism of TB resistance to multidrug in Qingdao, showing an association with the MDR. Pyrosequencing should be a good diagnostic tool for MDR-TB in Qingdao. PMID- 26379936 TI - Gallstone disease founded by ultrasonography in functional dyspepsia: prevalence and associated factors. AB - The aim of this study was to evaluate the frequency of gallbladder stone in functional dyspepsia (FD) by abdominal ultrasonography and to determine the factors associated with this frequency in Guilan province. A total of 195 subjects who referred to outpatient clinic of Razi Hospital, a tertiary referral center (Guilan, Iran) to evaluate FD were included in this study. They were interviewed by using a questionnaire and underwent ultrasonography. Among the 195 subjects were 18.5% male and 81.5% female. The overall frequency of Gallstones (GS) was 19% (37/195) with 17% males and 83% female. In patients with dyspepsia, the presence of fatty liver evidenced by ultrasonography was 67% (131/195). From 131 patients with fatty liver disease 24 (18.3%) have been reported GS. The most frequent symptom in all participants as well as patients with GS and patients with fatty liver was abdominal pain (69.7%, 81% and 66%, respectively) followed by excess flatus. Risk factor associated with increased odds ratios (ORs) for the development of gall stones was diabetes mellitus (OR = 2.63). It also showed that gallbladder wall thickening was more common in patients with GS (OR = 36.63). GS disease was not significantly related to the age, gender, fatty liver, renal stone, history of hypertension (HTN) and hyperlipidemia (HLP), alcohol consumption and smoking status. Patients with FD especially if they have diabetes should be referred for upper abdominal ultrasonography for screening and early detection of GS disease. PMID- 26379937 TI - Effect of obesity and hyperglycemia on benign prostatic hyperplasia in elderly patients with newly diagnosed type 2 diabetes. AB - PURPOSE: To investigate the relationship between blood glucose levels, age, body mass index (BMI), and benign prostatic hyperplasia (BPH) in patients with newly diagnosed type 2 diabetes. METHODS: A total of 141 BPH patients with newly diagnosed type 2 diabetes participated in this study. Their glucose level, international prostate symptom score (IPSS), prostate volume (PV), and maximum urinary flow rate (Qmax) were determined and analyzed. RESULTS: Compared to patients in 60-69 years of age, those in 70-79 years of age had higher IPSS and PV values (11.10+/-2.68 vs. 16.09+/-2.64, respectively; P<0.01; 38.67+/-4.65 vs. 44.76+/-2.84, respectively; P<0.01) as did patients >=80 y (11.10+/-2.68 vs. 19.87+/-3.35, respectively; P<0.01; 38.67+/-4.65 vs. 51.38+/-3.74, respectively; P<0.01). The Qmax was lower in the >=80 y group compared to the 60-69 y group (7.91+/-2.13 vs. 13.50+/-1.75, respectively; P<0.01). IPSS, PV, and insulin resistance index (HOMA-IR) were higher in patients with a BMI >=28 kg/m(2) group as compared to those with a BMI <24 kg/m(2) group. IPSS and PV values were higher in patients with HbA1c levels >=6.5% than in those with HbA1c<6.5% (16.30+/-3.31 vs. 9.87+/-1.07, respectively; P<0.01; 45.69+/-3.97 vs. 36.64+/-3.30, respectively; P<0.01), and the Qmax was lower (10.61+/-1.98 vs. 14.40+/-0.82, respectively; P<0.01). CONCLUSIONS: Aging, obesity, high glucose level, and insulin resistance increase the risk of BPH progression in elderly patients with newly diagnosed type 2 diabetes. Managing body weight and lowering the level of glycosylated hemoglobin may slow the progression of BPH in people with type 2 diabetes. PMID- 26379938 TI - Diagnostic value of Cyfra21-1, SCC and CEA for differentiation of early-stage NSCLC from benign lung disease. AB - Non-small cell lung cancer (NSCLC), which account for the most of lung carcinoma, is sometimes difficult to differentiate from benign lung diseases presented with nodular shadow in imaging scan. There is a need to find another non-invasive way to diagnosis early-stage NSCLC. To examine the potential diagnostic value of SCC, CFYRA 21-1 and CEA for the differentiation of early-stage NCSCL from benign lung diseases, we analyzed serum levels of tumor markers in 278 patients, including 248 patients with NSCLC and 30 patients with benign lung diseases. These benign lung diseases were presented with evidence of a high likelihood of having lung cancer. After surgical operation, diagnosis of lung cancer and benign lung disease were confirmed by histological examination. Preoperative tumor marker levels were quantified. Mann-Whitney U test was used to compare median levels of SCC, CFYRA 21-1 and CEA between the benign group and lung cancer group. Analysis of variance results were used for differences between different clinical stages of NSCLC. ROC was used to evaluate the diagnostic value of tumor markers. The median levels of Cyfra21-1, SCC and CEA were much higher in NSCLC than those in benign lung diseases. And we found that the mean levels of tumor marker were higher in advanced stage of NSCLC. The combination of tumor markers resulted in a higher sensitivity (91.3%) and a lower specificity (86.7%). In conclusion, the combination of positive SCC, positive CEA and positive Cyfra21-1 appear to be helpful in distinguishing early-stage NSCLC from benign lung disease which presented with suspicious pulmonary masses. PMID- 26379939 TI - Decreased mean platelet volume is associated with the developing stage of fetoplacental unit in spontaneous abortion. AB - AIM: The aim was to evaluate the place of mean platelet volume (MPV) in predicting spontaneous miscarriage and to identify any differences in its values following miscarriage after biochemical and clinical pregnancy. MATERIAL AND METHOD: We retrospectively evaluated the data of 305 spontaneous miscarriages and 168 control subjects. The miscarriage subjects were evaluated in two groups: miscarriage after biochemical pregnancy (n=79) (BA group) and miscarriage after clinical pregnancy (n=226) (CA group). Demographic and laboratory data of all subjects were statistically compared. RESULTS: No statistically significant difference was found between the miscarriage and control subjects in terms of demographic data and Hb, Htc, WBC, and Plt values. The mean platelet volume (MPV) value in the miscarriage group (8.99+/-1.47 fl) was statistically significantly lower than in the control group (9.66+/-1.64 fl) (P<0.001). A statistically significant difference was present between the BA, CA and control group, with the lowest MPV value in the BA group (8.64+/-1.34 fl, 9.11+/-1.49 fl, and 9.66+/-1.64 fl, respectively) (P<0.001). DISCUSSION: MPV was significantly lower in patients with miscarriage than the control group, and this was correlated with the gestational stage when the miscarriage occurred. PMID- 26379940 TI - Chinese medicinal plants for advanced endometriosis after conservative surgery: a prospective, multi-center and controlled trial. AB - The trial was to explore the effects of Chinese medicinal plants (CMP) treatment on the advanced endometriosis (stage III-IV) after conservative surgery. A prospective, multi-center and controlled trial was conducted from June 2012 to September 2013. Sixty-five post-operative women with advanced endometriosis (stage III-IV) after conservative surgery were included in the trial. They had undergone laparoscopic surgical excision of the endometriosis lesions and the diagnosis of endometriosis was confirmed by pathological examination. The patients received either CMP treatment or goserelin acetate sustained-release depot treatment (as comparison) according to the willingness of the patients. In the post-treatment follow-up visit at 6 and 12 months, the patients were respectively undergone ultrasonic and gynecological examinations. The serum levels of cancer antigen 125 (CA-125) and interleukin 18 (IL-18) were also detected in the post-treatment follow-up visit at 12 months. We found that in the post-treatment follow-up visit at 6 months, the recurrence rate of CMP group and comparison group was 1/31 (3.23%) and 1/34 (2.94%), respectively. In the post treatment follow-up visit at 12 months, the recurrence rate of CMP group and comparison group was 5/31 (16.13%) and 6/34 (17.65%), respectively. There were no significant differences between the two groups (P>0.05). The serum levels of CA 125 and IL-18 significantly decreased in both of the two groups (P<0.05) and no marked differences existed between them on the serum levels of IL-18 (P>0.05). The serum CA-125 levels of CMP group were significantly lower than those of the comparison group (P<0.05). No adverse effect was reported in both of the two groups during the research and the follow-up period. It concluded that CMP showed promise in preventing the recurrence of stage III-IV endometriosis after conservative surgery, although the conclusion is somewhat limited due to the small size of the trial. PMID- 26379941 TI - Skelate changes induced by orthodontic in class II division 1 by CBCT: a long term follow-up prospective study. AB - OBJECTIVE: To identify and evaluate changes in the sagittal position of point B due to orthodontic treatment using CBCT. MATERIALS AND METHODS: The subjects comprised 80 patients received fixed appliance. In this population, group 1 consisting of 40 patients with Class II division 2 malocclusion and group 2 consisting of 40 patients with minor crowding in the beginning of the treatment and required no or minimal maxillary anterior tooth movement. Treatment changes in incisor inclination, sagittal position of point B, SNB and movement of incisor root apex and incisal edge were calculated on pretreatment and post treatment on CBCT. RESULTS: Assessment of local changes in point B revealed that the point had moved backward. No significant change was observed in the value of the sella nasion-point B angle (SNB) in both the study and control groups. However, the changes of horizontal displacement after treatment in SNB between the two groups were found to be significant. There were no significant changes in the vertical and Z position of points B in both group. CONCLUSIONS: The position of point B was affected by local bone remodeling during orthodontic treatment. These changes significantly affect the SNB angle. PMID- 26379942 TI - EMP acupoint stimulation conducive to increase the effect of weight reduction through aerobic exercise. AB - PURPOSE: to observe whether weight reduction through aerobic exercise is more effective with the intervention of electromagnetic pulse (EMP) Acupoint stimulation. METHOD: based on the need of this study, we choose 48 young and middle-aged obese patients and randomly divide them into Experimental Group and Control Group with each group consisting of 24 of them. The Control Group has an aerobic endurance running each day with each running lasting for about 45 minutes and covering about 6 KM; the Experimental Group has the same exercise as the CG, but, after their running, stimulation by electromagnetic pulse meter is given to their Sanyinjiao Acupoint and Zushanli Acupoint. Then the content of body fat and the lipid indexes of the two groups before the treatment are compared with their counterparts after the said treatment. RESULT: after 6 weeks of treatment, the various indexes of the two groups are improved to different degrees (P<0.05); the effect on lipid indexes of the Experimental Group is obviously better than that of the Control Group (P<0.05), but the content of their body fat shows no conspicuous difference (P>0.05). CONCLUSION: after 6 weeks of treatment, the intervention of EMP acupoint stimulation can more evidently improve the lipid indexes than it has done to the group only having aerobic exercise; but it has little effect in terms of the improvement of the body fat content, which may be because of the short time of such intervention. PMID- 26379943 TI - Association of beta-fibrinogen gene polymorphism and plasma fibrinogen and allergic purpura nephritis. AB - OBJECTIVE: To investigate the association of beta-fibrinogen gene polymorphism with plasma fibrinogen and allergic purpura nephritis. METHODS: We designed a case-control study (334 case and 300 control) to genotype the beta-fibrinogen gene -455G/A polymorphism. The genotype and allele frequencies between the case and control group were compared. And we also compared the Fg concentration between different genotype. RESULTS: In the case group, there were 143 cases of GA type, accounting for 42.8%; there were 168 cases of GG type, accounting for 50.3%; there were 23 cases of AA type, accounting for 6.9%. While in the control group, GG type was the most common. There were 228 cases of GG type, accounting for 76%; there were 66 cases of GA type, accounting for 22%; there was 6 case of AA type, accounting for 2%. The frequency of Fgbeta-455G/A genotype between the two groups showed statistical significance (P<0.05). The levels of plasma Fg in the two groups showed statistical significance (P<0.01). In HSPN group Fgbeta GA and AA-type the concentration of Fg [(4.2 +/- 0.5) g/L], compared with the GG genotype [(3.1 +/- 0.4) g/L], was significantly increased with statistical significance (P<0.01). CONCLUSION: The Fgbeta-455G/A polymorphism was associated with the risk for HSPN and Fg concentration. PMID- 26379944 TI - Impact of estrogen-to-oocyte ratio on live birth rate in women undergoing in vitro fertilization and embryo transfer. AB - In order to evaluate whether the ratio of serum estrogen level on the day of human chorionic gonadotrophin (hCG) administration to number of oocyte retrieved has any impact on live birth rate in women undergoing in vitro fertilization (IVF), we retrospectively analyzed the clinical data from 7,112 women treated with GnRH-a long protocol in our center. Cycles were firstly divided into 6 groups according to the E2/oocyte ratio (< 150 pg/ml; 150~300 pg/ml; 300~450 pg/ml; 450-600 pg/ml; 600-750 pg/ml; >= 750 pg/ml). Live birth rate (39.4%) in women with E2/oocyte ratio >= 750 pg/ml was the lowest compared with that in other groups. We further divided the top 10% of patients into high estrogen group (E2/oocyte >= 740 pg/ml; n = 713). Compared with controls, those with high E2/oocyte ratio had significantly higher peak E2 level (6711.85 pg/ml versus 4670.89 pg/ml; P = 0.000) on the day of hCG administration; however, the live birth rate (39.27% versus 45.67%; P = 0.001) was significantly lower for women with high estrogen level. Thus, we conclude that high E2/oocyte ratio adversely affects live birth rate in women undergoing IVF treated with GnRH-a long protocol. PMID- 26379945 TI - Magnesium sulphate suppresses fentanyl-induced cough during general anesthesia induction: a double-blind, randomized, and placebo-controlled study. AB - Fentanyl-induced cough is a common phenomenon during anesthesia induction. Magnesium sulphate (MgSO4) is reported to have a powerful relaxation of airway smooth muscle. This study is to investigate the effects of prophylactic MgSO4 on the incidence and severity of fentanyl-induced cough. A total of 120 patients, scheduled for elective surgery under general anesthesia, were randomly allocated into three groups (n = 40, each group) and injected with 50 ml normal saline, 30 mg/kg and 50 mg/kg of MgSO4 (diluted with normal saline into 50 ml) in groups I, II and III, respectively. One minute later all patients were injected with 5.0 MUg/kg of fentanyl within 5 s. The incidence and severity of cough were recorded 30 s after fentanyl injection. Hemodynamic parameters and plasma magnesium concentration of the patients were also noted. Three patients dropped off the study due to obvious burning sense during injection of 50 mg/kg of MgSO4. Injection with 50 mg/kg of MgSO4 increased plasma magnesium level at the end of its infusion, but the latter still remained within therapeutic range (2-4 mmol/L). The incidence of cough in group I was much higher than those in groups II and III (45.0% vs. 15.0% and 8.1%, P < 0.05). Compared with the group I, both the groups II and III had lower incidence of moderate cough (P < 0.05). There were no differences in the hemodynamic data at three timepoints among the three groups. In conclusion, fentanyl-induced cough may be suppressed effectively and safely by prophylactic 30 mg/kg of MgSO4 during anesthetic induction. PMID- 26379946 TI - Correlation of mean platelet volume, neutrophil-to-lymphocyte ratio, and disease activity in children with juvenile idiopathic arthritis. AB - Juvenile idiopathic arthritis (JIA) is a chronic inflammatory arthritis characterized by periods of remission and relapse. Mean platelet volume (MPV) is an indicator of systemic inflammation. In the present study, we aimed to determine the association between mean platelet volume (MPV), neutrophil/lymphocyte ratio (NLR), platelet distribution width (PDW) and clinical measures of diseases activity in children with JIA. The study included 115 patients with JIA (64 with active disease and 51 with inactive disease) and 64 age-gender matched healthy control subjects. Routine laboratory methods were used to measure white blood cell count (WBC), platelet count (PLT), neutrophil count, lymphocyte count, hemoglobin (Hb), MPV, PDW, NLR, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) in all subjects of both the patient and control groups. Active disease was associated with significantly increased MPV (8.23 +/- 1.16 fl) compared with inactive disease (7.00 +/- 1. 08 fl) and control subjects (6.77 +/- 1.08 fl) P<0.001, P<0.001, P=NS, respectively). NLR was significantly higher in patients with active (2.11 +/- 1.19) and inactive (2.03 +/- 1.51) disease relative to the control subjects (1.33 +/- 0.66) (P<0.001, P=0.017, respectively). Mean PDW was significantly higher in patients with active disease (17.84 +/- 1.06) compared with the control group (17.19 +/- 0.93) (P=0.01). Our results suggest that MPV may be a useful marker of disease activity in patients with JIA. Regular treatment may decrease platelet activation in JIA patients. However, NLR was not a predictive marker of disease activity in patients with JIA. PMID- 26379947 TI - Comparison between photodynamic therapy with topical application of 5 aminolevulinic acid and CO2 laser therapy in the treatment of cervical condylomata acuminate: a randomized controlled trial. AB - The present study aimed to evaluate the efficacy of photodynamic therapy with topical applied 5-aminolevulinic acid (ALA-PDT) for the treatment of cervical condylomata accuminate (CA). 161 Patients with cervical CA were randomly divided into ALA-PDT group and CO2 laser (control) group. Patients (n=89) in the ALA-PDT group were treated with topical 5% ALA under occlusive dressing for 3 h followed by irradiation with semiconductor laser at a dose of 1000 J/cm(-2) and a power of 100 mW. Patients were treated 2 weeks later if necessary. Patients (n=72) in the control group were treated with CO2 laser. The treatment was repeated at 1-week interval when necessary. No response rate, complete response rate (CR) and recurrence rate of wart lesions as well as rate of eradication of HPVs were analyzed. The CR rate was 90.2% in the ALA-PDT group and 96.2% in the control group. The eradication rate was 90.2% in the ALA-PDT group and 65.8% in the control group after 3 months of follow-up. Both the eradication rate and recurrence rate in the ALA-PDT group were significantly lower than those in the control group (P<0.001). The adverse event in patients receiving ALA-PDT was mainly mild bleeding. ALA-PDT is a more effective and well-tolerated treatment for cervical CA compared with conventional CO2 laser therapy. PMID- 26379948 TI - Diabetes alters the blood glucose response to ketamine in streptozotocin-diabetic rats. AB - Ketamine is a commonly used short-acting anesthetic and recently attempted to treat pain which is a complication of diabetes. In this study we investigated the effect of ketamine on glucose levels of normal rats and diabetic rats. The results showed that no significance between the glucose levels in ketamine treatment group and saline treatment group at all time points was observed in normal rats. Ketamine did not produce hyperglycemia in normal fasted rats. However, ketamine dose dependently elevated glucose in diabetic rats from 80 mg/kg to 120 mg/kg at 1 hour after injection. The glucose did not return to the levels before treatment in streptozotocin (STZ) induced diabetic rats. Insulin revealed a powerful potency in decreasing glucose levels in diabetic rats. Ketamine did not induce acute hyperglycemia any more after diabetic rats pretreated with insulin. Serum corticosterone was significantly increased in all treatment groups including saline group after 1 hour treatment compared with baseline values. Then the corticosterone declined in both saline treatment groups. However, ketamine induced a more significant increase in corticosterone at 1 hour after injection compared with that of saline control group of diabetic rats. And no decline trend of corticosterone was observed after ketamine treatment 2 hours. Insulin did not reduce the elevated corticosterone level induced by ketamine either. The results suggested that the diabetic rats had a risk of hyperglycaemia when they were treated with ketamine. Pretreatment with insulin is a good symptomatic treatment for hyperglycaemia induced by ketamine. PMID- 26379949 TI - The value of HbA1c for diagnosing type 2 diabetes mellitus between Chinese Uyghurs and Hans in Xinjiang. AB - OBJECTIVE: To compare the difference of glycosylated hemoglobin (HbA1c) for diagnosing type 2 diabetes mellitus (T2DM) between Chinese Uyghurs and Hans in xinjiang. METHODS: we collected 707 subjects, including 456 Uyghurs and 251 Hans in Xinjiang Kashi region. All the subjects were underwent oral glucose tolerance test (OGTT) for diagnosing T2DM, at the same time their clinical biochemical markers and HbA1c levels were also measured. Then the data were analyzed, the receiver operating characteristic (ROC) curve was plotted and correlation analysis were made by SPSS 19.0 software. RESULTS: 1. The levels of body mess index (BMI), 2-hour plasma glucose (2 h PG), diastolic blood pressure (DBP) total cholestero (TC) and triglycerides (TG) were 26.6+/-4.75 kg/m(2), 14.3+/-6.2 mmol/l, 81.6+/-13.4 mmHg, 4.5+/-1.3 mmol/l and 4.3+/-2.8 mmol/l in Uyghurs, moreover those were higher than Hans [25.4+/-13.3 kg/m(2), 13.1+/-6.9 mmol/l, 78.4+/-9.9 mmHg, 2.3+/-2.1 mmol/l and 2.0+/-1.4 mmol/l, (P<0.05)]. 2. Otherwise, the optimal cut-off value for HbA1c to diagnose T2DM was 6.95% in Uyghurs. At this cut-off value, the sensitivity, specificity, positive likelihood ratio (+LR), negative likelihood ratio (-LR) and the area under the ROC curve (AUC) were 98.3%, 97.7%, 43.64, 0.017 and 0.997. While the optimal cut-off value was 7.05% in Hans, and, the sensitivity, specificity, +LR, -LR and AUC separately were 91.1%, 92.8%, 0.971, 12.6, 0.096 and 0.971. 3. The correlation analysis was made in two populations. It demonstrated that HbA1c was positively correlated with BMI, TC and TG in Uyghurs (r=0.138, 0.273, 0.482, P<0.05). However, in Hans, the HbA1c only was positively correlated with TG (r=0.178, P<0.05). CONCLUSION: The Uyghurs have higher metabolic markers, for example, BMI, TC, DBP and TG. It reveals that Uyghurs may have more severe insulin resistance (IR) comparing with Hans. And then, the cut-off value of HbA1c for diagnosing and screening T2DM is different between Uyghurs and Hans in Xinjiang. PMID- 26379950 TI - An in vitro and in vivo validation of a novel color-coded syringe device for measuring the intracuff pressure in cuffed endotracheal tubes. AB - BACKGROUND: The clinical practice of pediatric anesthesiology has changed with a transition to the use of cuffed endotracheal tubes (ETTs) in infants and children. The monitoring of intracuff pressure has been suggested as one means to limit the potential for damage to the tracheal mucosa. The current study evaluates the accuracy of a novel, color-coded syringe device which provides three zones (green, clear, and red) to estimate the intracuff pressure. METHOD: The study was conducted in two phases. Phase 1 was an in vitro study where cuffed ETTs of sizes 4.0 mm, 5.0 mm and 6.0 mm ID were placed into polyvinylchloride tubing of appropriate sizes. A manometer and the syringe device were simultaneously attached to measure the intracuff pressure at the middle of the 3 different zones on the device (red, clear, and green). Phase 2 was an in vivo study where the syringe device and the manometer were simultaneously attached to the pilot balloon to measure the intracuff pressure and the corresponding zone on the color-coded syringe following endotracheal intubation. Statistical analysis included a descriptive reporting of the mean +/- SD, median, range, and 95% confidence intervals (CI) of the actual intracuff pressure readings at the three zones of the syringe device during both its in vitro and in vivo use. RESULTS: For phase 1 of the study, the 95% CI for the green, clear, and red zones were 21.5-21.8, 29.2-29.5, and 46.5-47.4 cmH2O respectively. This correlated well with the manufacturer reported values of 20-30, 30-40, and 40-60 cmH2O for the 3 zones (green, clear, and red respectively). Phase 2 of the study included 200 patients ranging in age from 0.1 to 21.8 years (6.7 +/- 5.1 years) and in weight from 4.0 to 129.1 kilograms (29.4 +/- 23.3 kgs). The size of the ETTs ranged from 3.0 to 7.0 mm ID. The intracuff pressure measured by the manometer ranged from 4 to 65 cmH2O (27.6 +/- 9.7 cmH2O). The 95% CI for the green, clear, and red zones were 20.5-21.7, 27.7-29.1, and 41.2-46.5 cmH2O respectively. There was no significant differences noted when comparing different patient ages or sizes of ETT. CONCLUSION: The current study demonstrates a clinically acceptable correlation between the zones on this novel, color-coded syringe device and the actual measurement of the intracuff pressure obtained by a manometer for both in vitro and in vivo use. This device is a simple, reliable, portable and affordable method to monitor intracuff pressure. PMID- 26379951 TI - Efficacy and safety of different doses of tirofiban combined with ticagrelor on diabetic patients with AMI receiving in emergency percutaneous coronary intervention (PCI). AB - OBJECTIVE: The aim of this study was to investigate the efficacy and safety of dual antiplatelet drugs combined with different doses of tirofiban on diabetic patients with acute myocardial infarction (AMI) receiving emergency percutaneous coronary intervention (PCI). METHODS: 158 diabetic patients with AMI undergone emergency PCI were randomly divided into three groups: Group A (53 cases) as the control group-dual anti-platelet agents (aspirin + ticagrelor); Group B (52 cases)-dual anti-platelet agents + conventional dose of tirofiban [10 MUg/kg by PCI and 0.15 MUg/(kg.min) by continue venous pump for 24 h]; Group C (53 cases) dual antiplatelet agents + half-dose tirofiban [10 MUg/kg by PCI and 0.075 MUg/(kg.min) by continue venous pump for 24 h]. RESULTS: Compared with group A, thrombolysis in myocardial infarction 3 (TIMI3) blood flow and TIMI myocardial perfusion grade 3 (TMPG3) myocardial perfusion of patients in group B and group C after PCI was significantly higher (P < 0.05), the average day of hospitalization was significantly shorter (P < 0.05), reinfarction during hospitalization, post infarction angina, severe arrhythmia, the incidence of cardiac function above KillipIII level was significantly lower (P < 0.05). And the differences between group B and C was not statistically significant (P > 0.05). Severe bleeding and moderate incidence of bleeding in group B was significantly higher than that in group A and group C (P < 0.05). CONCLUSIONS: Based on combination of dual the anti-platelet agents and ticagrelor for diabetic patients with AMI receiving PCI, the combination of half-dose tirofiban can effectively improve TIMI flow and TMPG myocardial tissue perfusion, and reduce the incidence of major adverse cardiac events (MACE) and severe bleeding. PMID- 26379952 TI - Paternal factors to the offspring birth weight: the 829 birth cohort study. AB - OBJECTIVE: To investigate the contributions of parental, especially paternal factors to the offspring birth weight. METHODS: Eligible 829 live-born, singleton children living in Hubei, China were recruited. Birth weight were measured immediately after birth and information about the parents were collected by face to-face interview using questionnaire. Association between parental factors and birth weight was evaluated using univariate linear regression and multinomial logistic regression models. RESULTS: Fathers living in the rural area had offspring with higher risk of low birth weight when compared with fathers who live in the capital city. Maternal lower education, lower gestational weight gain, being primipara and shorter gestational age were risk factors for low birth weight. In addition, Mothers with the history of chronic disease had higher risk to deliver a low birth weight baby. On the contrary, women who increased non staple food consumption during pregnancy had higher risk to have a macrosomic pregnancy. However, lifestyle factors including diet, exercise, screen time, drinking and smoking from both maternal and paternal exhibited little influence on fetal birth weight. CONCLUSION: Paternal as well as maternal factors exert influence on the fetal birth weight, although maternal factors make bigger contributions. Compared with socioeconomic and obstetric factors, lifestyle before and during pregnancy has less influence on fetal birth weight, suggested that special attention should be paid to antenatal care for the pregnant women with lower socioeconomic status in rural area. PMID- 26379954 TI - Effects of dexmedetomidine on anesthesia recovery period and postoperative cognitive function of patients after robot-assisted laparoscopic radical cystectomy. AB - OBJECTIVE: The purpose of the study was to evaluate the neuroprotective effect of dexmedetomidine on anesthesia recovery period and postoperative cognitive function of patients after robot-assisted laparoscopic radical cystectomy and ileal conduit diversion. METHODS: A total of 40 elective patients who would undergo robot-assisted laparoscopic radical cystectomy and ileal conduit diversion. They were randomly divided into two groups in a double-blind manner. After pneumoperitoneum established, all patients adopted 40 degrees trendelenberg position. Mean arterial pressure (MAP), heart rate (HR), and bispectral index (BIS) of each patient were recorded at four moments respectively, namely the end of surgery (T0), palinesthesia (T1), extubation (T2), 10 min after extubation (T3). RESULTS: In the dexmedetomidine group, the mean arterial pressure and heart rate decreased at T1 and T2 compared with controls (P<0.05); in addition, the delirium rating scale was lower than the latter (P<0.05) while Ramsay sedation score was significantly higher (P<0.05). POCD was observed on 28 patients, containing 17 controls and 11 dexmedetomidine individuals, one day after operation, and 21 patients (12 controls, 9 dexmedetomidine people) five days after operation. One- and five-day after operation, the levels of TNF-alpha, NSE and IL-6 in the dexmedetomidine group were significantly lower than those in the control group (P<0.05), and serum SOD significantly increased in the former (P<0.05). CONCLUSION: Dexmedetomidine had a neuroprotective effect on anesthesia recovery and postoperative period of the elderly patients undergone robot-assisted laparoscopic radical cystectomy, which might be related to the reduction of inflammatory reaction induced by dexmedetomidine. PMID- 26379953 TI - An epidemiological study of risk factors of thyroid nodule and goiter in Chinese women. AB - Thyroid nodule (TN) and goiter are two common disorders of the thyroid. Despite their benign nature, both conditions are associated with multiple pathologic conditions including thyroiditis, endocrine dysregulation, and autoimmune disease. In this study we conducted a large-scale epidemiological study in Chinese women to identify risk factors implicated in the pathogenesis of TN and goiter. We analyzed demographic data, medical history, menstrual status, smoking, alcohol consumption, body height, weight, waist circumference, and body mass index (BMI). Thyroid ultrasonography was performed for all subjects. Our results showed that age, menstrual status, BMI, waist circumference, hypertension, dyslipidemia and hyperglycemia had a significant relationship with the prevalence of TN and goiter. There was also a significant association between parity, educational level, smoking, seafood consumption, salt consumption and TN. Waist hip ratio, BMI, and triglyceride had a significant association with both TN and goiter, and total cholesterol only correlated with TN. Medical management of hypertension significantly affected TN prevalence. Our study also demonstrated age to be a strong predictor of TN and goiter, and obesity a predictor of the likelihood of developing goiter. Thus, our study suggests that the female Chinese population with advance age, menopause, obesity and metabolic syndrome be examined for TN and goiter, and those patients with confirmed TN and goiter be screened for age and obesity related disorders such as metabolic syndrome. PMID- 26379955 TI - Different study conditions between dental students in China and Japan. AB - BACKGROUND: The purpose of this study was to compare the study conditions of dental students towards dental education in China and Japan. METHODS: 60 students from the Stomatology School of China Medical University and 51 students from the Dental Faculty of Kyushu University, Japan, participated in this study. Information was derived from a self-answered questionnaire consisting of 10 items. RESULTS: More Japanese students (60%) compared to Chinese students (28%) were satisfied with their lives in dental school. For the main reason of discontent, 23.5% of the Japanese students attributed to busy study and lacking of spare time, while 38.3% of the Chinese students indicated small campus lacking of infrastructure. CONCLUSIONS: Both students of two countries think they were in big pressure. The main stressor of Japanese students was the examination, but that of Chinese students was anxiety of their future and obtains employment. The main source of tuition and maintenance was family in the both countries, but more Japanese students (25.5%) were dependent on scholarship compared with Chinese students (3.3%). CLINICAL IMPLICATIONS: The findings from this study enhance our understanding of study conditions among dental students and help to define strategies to improve student management in both Japan and China. PMID- 26379956 TI - Outcomes of transradial primary percutaneous intervention from a tertiary cardiac centre in Turkey. AB - OBJECTIVES: The aim was to study transradial approach (TRA) and transfemoral approach (TFA) in terms of feasibility, effectiveness, usefulness, and procedure characteristics in patients having ST-segment elevation myocardial infarction (STEMI) and undergoing primary percutaneous coronary intervention (PCI). Along with the said aim, major adverse cardiovascular events (MACE) at follow-up were also compared. METHODS: The present study was conducted on 344 consecutive patients having ST-segment elevation myocardial infarction and qualifying for PCI. Patients were classified into two groups according to radial and femoral approaches. Patients were followed-up for MACE. RESULTS: PCI was found to be successful in all patients. In TRA group the time between the end of the intervention to removal of the sheath, and duration of mobilization and hospitalization were significantly shorter when compared to TFA group (12 +/- 2 minutes vs. 240 +/- 12 minutes; P = 0.001, 13 +/- 2 hours vs. 22 +/- 2 hours; P = 0.001, and 96 +/- 45 hours vs. 125 +/- 55 hours; P = 0.001, respectively). In TRA group, two patients had hematomas greater than 2 cm while fourteen patients in TFA group had hematomas greater than 5 cm (1% vs. 8%; P = 0.002). TRA group had lower in-hospital MACE rates (5% vs. 11%; P = 0.036). The long terms MACE rates of the groups were similar (23% vs. 22%; P = 0.888). CONCLUSIONS: In patients with STEMI, PCI via TRA had the same effectiveness as TFA. Moreover, Time to ambulation and rates of bleeding complications were reduced by TRA, which allowed early rehabilitation. TRA reduced the incidence of in-hospital MACEs. PMID- 26379957 TI - Relationship between menopause and periodontal disease: a cross-sectional study in a Portuguese population. AB - BACKGROUND: Menopause is associated with important systemic and oral changes. Many researchers have tried to evaluate the influence of hormonal changes associated with menopause in the periodontium, however results are contradictory. OBJECTIVE: Evaluate the possible effects of menopause on the severity of periodontal disease and tooth loss, by considering several general, oral and periodontal parameters. METHODS: 102 women with chronic periodontitis, and at least six teeth, were divided into two groups: a study group (SG) consisting of 68 menopausal women and a control group (CG) consisting of 34 premenopausal women. The participants had extensive anamnesis, made by a single senior periodontologist, which collected demographic data, medical and gynaecological history and habits. Additionally, oral and periodontal parameters including: number of teeth, plaque index, presence of calculi, probing depth, bleeding on probing, gingival recession and attachment loss were recorded. The following statistical tests were used: Chi-square, Fisher's t-test for independent samples, non-parametric Wilcoxon-Mann-Whitney, and linear multiple regression. RESULTS: The number of teeth was significantly lower in postmenopausal women (SG 10.8 +/- 5.9, CG 6.8 +/- 4.6), however, after adjusting for age, smoking and plaque index, the difference was no longer statistically significant (P=0.169). The attachment loss was slightly higher in the study group, although the difference is not significant (SG 4.31 +/- 1.08, CG 4.05 +/- 1.28). CONCLUSIONS: Menopause does not appear to significantly influence the severity of periodontal disease and tooth loss. Other factors may exert a greater influence on the progression of periodontal disease rather than menopause itself. PMID- 26379958 TI - Association of hematological indicies with diabetes, impaired glucose regulation and microvascular complications of diabetes. AB - In recent years, there has been renewed interest in hematological parameters as predictors of endothelial dysfunction and inflammation. The aim of our study is to evaluate the relationship between HbA1c and hematological indices, and to evaluate the relationship between these parameters and microvascular complications of diabetes. Three hundred and seven diabetic patients (124 male, 183 female; mean age 50.8+/-8.5), and 187 controls (76 male, 111 female; mean age 51.1+/-10.1) were included in the study. In the diabetic group, mean platelet volume (MPV), plateletcrit (PCT), platelet distribution width (PDW), white blood cell count (WBC), platelet count, platelet to lymphocyte ratio (PLR) and neutrophil to lymphocyte ratio (NLR) were significantly higher than the control group (P<0.05). Diabetic patients were divided into two group according to their HbA1c levels (Group 1; HbA1c <7 (n=82) and group 2; HbA1c >=7 (n=225)). Mean platelet volume, PCT and PDW levels were significantly increased in group 2. Mean platelet volume was significantly increased in diabetic patients with retinopathy compared to those without retinopathy (P=0.006). The neutrophil to lymphocyte ratio and PLR levels were significantly higher in patients with nephropathy (P=0.004, P=0.004 respectively). There was statistically significant difference of lymphocyte count between patients with and without neuropathy. In correlation analysis, positive correlation between HbA1c and PCT (rs=0.192, P<0.001), HbA1c and PDW (rs=0.305, P<0.001), HbA1c and MPV (rs=0.352, P<0.001) were determined. In binary logistic regression analysis; WBC, PDW and PLR levels were found to be independently associated with diagnosis of diabetes while WBC, MPV, PLR and NLR levels were found to be independently associated with impaired glucose regulation. This study demonstrates that altered hematological indices are closely associated with HbA1c levels in individuals with and without diabetes and some of these parameters are associated with diabetic microvascular complications. These associations may be explained by connection between these easy accessible and inexpensive hematological indices and inflammation, tendency to coagulation and thrombosis in patients with diabetes. PMID- 26379959 TI - Association of apneic oxygenation with decreased desaturation rates during rapid sequence intubation by a Chinese emergency medicine service. AB - Rapid and safe airway management has always been of paramount importance in successful management of critically ill and injured patients in the emergency department. The achievement rate of emergency medicine inhabitants in airway management improved enhanced essentially subsequent to finishing anaesthesiology turn. There was a slightly higher rate of quick sequence intubation in the postapneic oxygenation groups (preapneic oxygenation 6.4%; postapneic oxygenation 9.1%). The majority of patients intubated in both groups were men (preapneic oxygenation 72.3%; postapneic oxygenation 63.5%). A higher percentage of patients in the preapneic oxygenation group had a Cormack-Lehane grade III or worse view (23.2% versus 11.8%). Anaesthesiology turns should be considered as an essential component of emergency medicine training programs. A collateral curriculum of this nature should also focus on the acquisition of skills in airway management. PMID- 26379960 TI - Relationship between the total length of the stents and patients' quality of life after percutaneous coronary intervention. AB - The aim of this study was to examine the relationship between the total length of the stents and the postoperative life quality of patients with multi-vessel coronary artery disease who undergo percutaneous coronary intervention (PCI). Using the short-form health survey (SF-36) items, we analyzed the data on the postoperative life quality of 166 patients with multi-vessel coronary artery disease who underwent percutaneous transluminal coronary intervention in the Department of Cardiology of the First Affiliated Hospital of Henan University of Science and Technology from September 2011 to September 2013. Follow-up was performed 6 months later. All of the dimensionalities, except general health and mental health, showed significantly higher scores after PCI. No significant relationships were observed between the total length of the stents and the postoperative life quality of patients with multi-vessel coronary artery disease who underwent PCI. PCI can effectively improve the postoperative life quality of patients; however, there was no significant relationship between the total length of the stents and postoperative life quality of patients. PMID- 26379961 TI - Mortal quintet of sickle cell diseases. AB - BACKGROUND: Sickle cell diseases (SCDs) are chronic inflammatory processes on capillary level. We tried to understand some possible correlations between stroke and severity of SCDs. METHODS: All patients with SCDs were taken into the study. RESULTS: The study included 343 patients (174 males and 169 females). There were 30 cases (8.7%) with stroke. The mean ages were similar in both groups (32.5 versus 29.1 years in the stroke group and other, respectively, P>0.05). The female ratios were similar in both groups, too (43.3% versus 49.8%, respectively, P>0.05). Prevalences of associated thalassemia minors were also similar in them (73.3% versus 65.1%, respectively, P>0.05). Smoking was higher among the stroke cases, significantly (26.6% versus 13.0%, P<0.05). Mean white blood cell count, hematocrit value, and mean platelet count of the peripheric blood were similar in both groups (P>0.05 for all). On the other hand, although the painful crises per year, tonsilectomy, priapism, ileus, pulmonary hypertension, chronic obstructive pulmonary disease, coronary heart disease, chronic renal disease, rheumatic heart disease, avascular necrosis of bones, cirrhosis, and mortality were all higher in the stroke group, the differences were only significant for acute chest syndrome (ACS), digital clubbing, and leg ulcers (P<0.05 for all), probably due to the small sample size of the stroke group. CONCLUSION: SCDs and smoking are chronic destructive processes on endothelium, and both terminate with early organ failures in life. Probably smoking, digital clubbing, leg ulcers, ACS, and stroke are mortal quintet of the SCDs that may indicate shortened survival in such patients. PMID- 26379962 TI - Oxidative stress parameters and their correlation with clinical, metabolic and polysomnographic parameters in severe obstructive sleep apnea syndrome. AB - The aim of the present study was to assess the levels of oxidative stress markers, catalase (CAT), glutathione peroxidase (GPX) and malondialdehyde (MDA) in severe OSAS and to investigate any correlation between oxidative stress markers and clinical, metabolic and polysomnographic parameters. A total of 30 patients with severe OSAS and 30 healthy controls were included in this cross sectional, clinical study. Demographic data, polysomnographic, biochemical and clinical indices as well as serum levels of CAT, MDA and GPX were measured and compared in OSAS and control groups. Furthermore, OSAS patients with and without pulmonary hypertension (PHT) were evaluated in terms of levels of CAT, MDA and GPX. Patients with severe OSAS exhibited significantly lower serum levels of CAT (P<0.001) and GPX (P<0.001). Serum MDA levels were remarkably higher in OSAS group (P<0.001). Correlation analysis revealed that levels of CAT and GPX were correlated with apnea-hypopnea index and there was a correlation between serum levels of MDA and CRP. Severe OSAS patients with and without PHT did not reveal any differences for CAT (P=0.789), MDA (P=0.805) and GPX levels (P=0.281). Our results have shown that oxidative stress markers significantly changed in patients with severe OSAS. This information is noteworthy because documentation of the role of oxidative stress in OSAS may have important implications regarding diagnosis, monitoring, treatment and prognosis. PMID- 26379963 TI - Clinical significance of dynamic monitoring by transcranial doppler ultrasound and intracranial pressure monitor after surgery of hypertensive intracerebral hemorrhage. AB - The aim of this study was to investigate the surgical method of hypertensive intracerebral hemorrhage (HIH) and how to control the postoperative blood pressure. 96 HIH patients were performed the craniotomic hematoma dissection (CHD) and the hematoma-cavity drilling drainage (HCDD), respectively. Meanwhile, the intracranial pressure and mean arterial pressure of each patient were continuously monitored for 7 days, the postoperative 1(st), 3(rd), 7(th) and 14(th)-day average flow velocities and pulsatility indexes of the bilateral middle cerebral arteries were monitored. CHD exhibited the significant difference in the long-term quality of life (ADL classification 6 months later) of patients with hematoma >50 ml than HCDD; furthermore, the postoperative 1(st), 3(rd), 7(th) and 14(th)-day TCD parameter analysis revealed that CHD exhibited better results in relieving the intracranial pressure and improving the cerebral blood flow than HCDD, and the postoperative ICP and MAP monitoring towards all patients could effectively control the blood pressure and prevent the further bleeding. The patients with hematoma >50 ml should choose CHD, and all HIH patients should be routinely performed the ICP and MAP monitoring. PMID- 26379964 TI - An investigation into the in-vitro effectiveness of electrolyzed water against various microorganisms. AB - The aim of this study was to investigate the in-vitro antimicrobial activity of usage and normal concentrations of electrolyzed water in hospital. In our study, the effects of different concentrations of electrolyzed water named Envirolyte(r) (Industries International Ltd., Estonia) on two gram positive, four gram negative standard strains and clinical isolates of four gram negative, two gram positive, one spore-forming bacillus and Myroides spp strains that lead to hospital infections were researched. The effects of different concentrations and different contact times of Envirolyte(r) electrolyzed water on cited strains were researched through method of qualitative suspension tests. Petri dishes fo bacteria have been incubated at 37 degrees C 48 hours. Bactericidal disinfectant was interpreted to be effective at the end of the period due to the lack of growth. Solutions to which disinfectant were not added were prepared with an eye to control reproduction and controlcultures were made by using neutralizing agents. 1/1, 1/2, and 1/10 concentrations of Envirolyte(r) electrolyzed water were found to be effective on the bacteria that lead to hospital infections used during all test times. As a conclusion, based upon the results we acquired, it was observed that Envirolyte(r) electrolyzed water of 100% concentration would be convenient to be used for disinfection when diluted to a usage concentration of 1/10. PMID- 26379965 TI - Associations of immunity-related single nucleotide polymorphisms with overall survival among prostate cancer patients. AB - The progression of prostate cancer is influenced by systemic inflammation, and may be attributed, in part, to genetic predisposition. Single nucleotide polymorphisms associated with the immune response may help mediate prostate cancer progression. We analyzed data from a hospital-based case-control study of 164 prostate cancer patients and 157 healthy male controls from the Memorial Sloan Kettering Cancer Center. We evaluated associations between six immunity related polymorphisms (CRP rs1205 and rs1800947, FGFR2 rs1219648 and rs2981582, IFNGR1 rs11914, and IL10 rs1800871) and overall survival among prostate cancer patients, calculating adjusted hazard ratios (HR) and 95% confidence intervals (CI) using Cox proportional hazards regression. FGFR2 rs1219648 (GG vs. AA) and rs2981582 (TT vs. CC) polymorphisms were associated with more favorable overall survival (HR: 0.13, 95% CI: 0.03-0.62 and HR: 0.13, 95% CI: 0.03-0.53, respectively) in patients with primary prostate cancer. These observations highlight the need to validate and identify these and other immunity-related polymorphisms in larger studies examining survival of prostate cancer patients. PMID- 26379966 TI - Hemodynamic responses to endotracheal intubation performed with video and direct laryngoscopy in patients scheduled for major cardiac surgery. AB - This study aims to compare the hemodynamic responses to endotracheal intubation performed with direct and video laryngoscope in patients scheduled for cardiac surgery and to assess the airway and laryngoscopic characteristics. One hundred ten patients were equally allocated to either direct Macintosh laryngoscope (n = 55) or indirect Macintosh C-MAC video laryngoscope (n = 55). Systolic, diastolic, and mean arterial pressure, and heart rate were recorded prior to induction anesthesia, and immediately and two minutes after intubation. Airway characteristics (modified Mallampati, thyromental distance, sternomental distance, mouth opening, upper lip bite test, Wilson risk sum score), mask ventilation, laryngoscopic characteristics (Cormack-Lehane, percentage of glottic opening), intubation time, number of attempts, external pressure application, use of stylet and predictors of difficult intubation (modified Mallampati grade 3-4, thyromental distance < 6 cm, upper lip bite test class 3, Wilson risk sum score >= 2, Cormack-Lehane grade 3-4) were recorded. Hemodynamic parameters were similar between the groups at all time points of measurement. Airway characteristics and mask ventilation were no significant between the groups. The C-MAC video laryngoscope group had better laryngoscopic view as assessed by Cormack-Lehane and percentage of glottic view, and a longer intubation time. Number of attempts, external pressure, use of stylet, and difficult intubation parameters were similar. Endotracheal intubation performed with direct Macintosh laryngoscope or indirect Macintosh C-MAC video laryngoscope causes similar and stable hemodynamic responses. PMID- 26379967 TI - Association between polymorphisms in APE1 and XRCC1 and the risk of gastric cancer in Korean population. AB - The DNA repair system plays a pivotal role in maintaining genomic integrity and protection against mutations that could lead to cancer development. The aim of this study was to explore the association between common polymorphisms of DNA repair genes, APE1 (rs1760944 and rs1130409) and XRCC1 (rs1799782, rs25487, and rs25489), and gastric cancer (GC) risk in the Korean population. We conducted a case-control study of 368 GC patients and 398 controls by using TaqMan genotyping assay. None of the polymorphisms was associated with the risk of GC. Further analysis showed a lack of association between APE1 and XRCC1 polymorphisms or haplotypes and the risk of GC and GC subgroups. The heterozygous CT genotype of XRCC1 rs25487 was related to 1.94 times increased risk of lymph node metastasis (LNM) in diffuse type GC compared to the XRCC1 rs25487 CC genotype (adjusted OR = 1.94, 95% CI = 1.06-3.53, P = 0.031) after adjusting for gender and age, whereas the remaining polymorphisms showed no association with GC or GC subgroups. This result suggests that genetic variation of XRCC1 rs25487 could be a risk factor for LNM in diffuse type of GC in the Korean population. PMID- 26379968 TI - The correlation between HLA-DRB1 and HLA-DQB1 gene polymorphisms and cytokines in HPV16 infected women with advanced cervical cancer. AB - OBJECTIVE: To analyze the distribution of HLA-DRB1 and HLA-DQB1 alleles and its correlation with IFN-gamma, IL-2, IL-6, IL-10 in HPV16 infected women with advanced cervical carcinoma. METHODS: We collected 137 blood samples of cervical carcinoma patients diagnosed by pathology as cervical cancer in stage IIb-IVb before the treatment, and we gathered 175 blood samples of healthy women living in the local. We determined the genetic subtypes of HLA-DRB1 and HLA-DQB1, and we measured the concentration of IFN-gamma, IL-2, IL-6 and IL-10. We compared the difference of cytokines in patients with different clinical stages and the healthy in the control group. According to genetic subtypes of HLA-DRB1 and HLA DQB1, we also compared the concentration of cytokine (CK) in different genetic subtypes. RESULTS: Eight HLA-DRB1 alleles and four HLA-DQB1 alleles were found. There were not significant differences between each allele in the concentration of IFN-gamma, IL-2, IL-6, and IL-10. CONCLUSION: HLA-DRB1*07, HLA-DQB1*02 and HLA DQB1*03 were the differentially expressed gene in HPV16 infected patients with advanced cervical cancer. There may be correlations between the occurrence, development of cervical cancer and IFN-gamma, IL-2, IL-6, IL-10. PMID- 26379969 TI - Escopoletin treatment induces apoptosis and arrests cell cycle at G0/G1 phase in the oral squamous cancer cell lines. AB - This study was aimed to investigate the antiproliferative effect of escopoletin on CAL 27 and CAL 33 oral squamous cancer cell lines. MTT assay and flow cytometry were used for the analysis of escopoletin effect on cell viability and apoptosis, respectively. Western blot analysis was used for the examination of cyclin and cyclin-dependent kinase expression after treatment of CAL 33 cells with escopoletin. The results showed a marked decrease in the viability of CAL 27 and CAL 33 cell lines after 48 h of escopoletin treatment. Treatment of CAL 33 cells with escopoletin led to the induction of apoptosis and arrest of cell cycle at G0/G1 phase. In the cells treated with escopoletin cyclin D1 and E expression was reduced and CDK1 expression was inactivated. The above findings suggest that escopoletin exhibits inhibitory effect on the oral squamous cancer through induction of apoptosis and arrest of cell cycle. Therefore escopoletin can be a promising candidate for the prevention of oral squamous cancer. PMID- 26379970 TI - A comparison on the prevalence and outcomes of gestational versus type 2 diabetes mellitus in 1718 Saudi pregnancies. AB - The presence of either diabetes mellitus type 2 (DMT2) or GDM constitute a high risk pregnancy. Given the high rate of DMT2 and GDM in the kingdom of Saudi Arabia (KSA), no study has ever compared whether GDM outcomes are comparable to those with DMT2. The present study aims to compare for the first time, maternal and neonatal outcomes among Saudi patients with GDM, DMT2 and non-DM groups. This is a retrospective study covering data from 1718 pregnant patients admitted at King Fahad Medical City, Riyadh, KSA from April 2011 to March 2013. The prevalence of GDM was 13.8%, DMT2 was 0.9%. DMT2 group had the highest mean parity and shortest mean gestational age as compared to other groups. Half of all the subjects in the DMT2 group also experienced preterm labor, as opposed to only 10% in GDM and 14% in the non-DM group, respectively. Finally, neonates delivered by DMT2 mothers had the highest percentage of admissions to NICU (33%) as compared to 10% in the non-DM group and only 5% in the GDM group. Outcomes of the GDM group are almost comparable with the non-DM group. While the results of the present study reflect the efficient management of GDM cases in Saudi patients, DMT2 complicated pregnancies, which are considered to be at a much higher risk for maternal and neonatal complications, should be given equally special attention. PMID- 26379971 TI - Fasting blood glucose levels affect hospitalization time and relapse and mortality rates of cerebral infarction patients. AB - OBJECTIVE: This study determined the relationship between fasting glucose levels of cerebral infarction patients and the hospitalization time and relapse and mortality rates. METHODS: A retrospective study was conducted between February 1996 and December 2006 involving 974 inpatients with cerebral infarctions. Fasting blood glucose and lipid levels and blood pressure were measured the morning after hospitalization. The length of hospital stay, and data obtained from telephone follow-up interviews regarding relapse and complications were recorded. The data were analyzed using multiple linear regressions, logistic regression, the chi-square test, and the Kruskal-Wallis analysis of variance of ranks test. RESULTS: Our data show that the duration of hospitalization and relapse and mortality rates of patients with cerebral infarctions correlate with the admission fasting blood glucose levels. Cerebral infarction patients with fasting blood glucose levels > 11.1 mmol/L and LDL levels > 3.5 mmol/L have higher mortality rates (50.00%). Patients with fasting blood glucose levels > 11.1 mmol/L combined with a diastolic pressure < 80 mmHg or > 100 mmHg also have high mortality rates (33.33% and 30.00%, respectively). CONCLUSIONS: Fasting glucose levels of inpatients with cerebral infarctions are closely related to the duration of hospitalization and relapse and mortality rates. Higher fasting blood glucose levels exacerbate damage to cerebral blood vessels caused by alterations in blood lipid levels and blood pressure. Therefore, blood glucose levels should be monitored during the early stage of cerebral infarction and intervention should be provided promptly to decrease the length of hospital stay and the risk of relapse and mortality. PMID- 26379972 TI - Association of ADRB1 gene polymorphisms with pain sensitivity in a Chinese population. AB - OBJECTIVE: The present study aims to observe the influence of single-nucleotide polymorphisms (SNPs) in the ADRB1 gene on individual differences in pain sensitivity. METHODS: We analyzed the associations between pain sensitivity and ADRB1 gene SNPs (A145 G and G1165 C) in 324 Chinese patients who underwent surgery. The genotyping was performed using PCR-RFLP technique. RESULTS: The patients who carried the A-allele of the A145 G SNP were more sensitive to cold pressor-induced pain than those who did not carry this allele (P < 0.05). We did not found G1165 C polymorphism associated with pain sensitive in the present study. The haplotype analysis revealed A-C haplotype carriers have reduced fentanyl use in 24-h postoperative (P < 0.05). CONCLUSION: ADRB1 gene polymorphisms are associated with pain and analgesic sensitivity. PMID- 26379973 TI - Cytotoxic T lymphocyte-associated antigen-4 +49A>G polymorphism and the risk of non-small cell lung cancer in a Chinese population. AB - BACKGROUND: CTLA-4 is a potent immunoregulatory molecule and plays a pivotal role in the negative regulation of T-cell proliferation and activation. Previously, the association between CTLA-4 +49A>G polymorphism and the risk of NSCLC has been investigated in several studies, however, their results were inconsistent. Therefore, we aimed to investigated the association between CTLA-4 +49A>G polymorphism and the risk of NSCLC in a Chinese population. METHODS: We recruited 231 NSCLC patients and 250 healthy controls in the present case-control study. PCR-RFLP was used to analyze the polymorphism of CTLA-4. The chi-squared test was used to examine differences between NSCLC patients and controls. The odds ratio (OR) and its 95% confidence interval (95% CI) were obtained by logistic regression methodology to determine correlations between the CTLA-4 polymorphism and the incidence of NSCLC. RESULTS: When the AA genotype was used as the reference group, the GG genotype was significantly associated with increased risk for NSCLC (OR=2.181, 95% CI: 1.244-5.198; P=0.007), however, the AG genotype was not significantly associated with increased risk for NSCLC (OR=2.018, 95% CI: 0.826-3.881; P=0.099). Under the dominant model of inheritance, the AG+GG genotype was significantly associated with increased risk for NSCLC (OR=3.271, 95% CI: 1.827-4.559; P=0.015). In addition, the G allele had a 2.754-fold higher risk of NSCLC in comparison with the A allele (OR=2.754, 95% CI: 1.365-6.891, P=0.005). CONCLUSIONS: Our data provided evidence that the CTLA-4 +49A>G polymorphism is associated with increased risk of NSLCL in Chinese population. PMID- 26379974 TI - TGF-beta1-509C/T polymorphism and the risk of ESCC in a Chinese Han population. AB - BACKGROUND: The studies investigating whether transforming growth factor (TGF) beta1-509C/T polymorphism is associated with the risk of ESCC is inconsistent. METHODS: The TGF-beta1-509C/T genotypes were determined by using a polymerase chain reaction (PCR)-restriction fragment length polymorphism assay and DNA sequencing analysis. The differences in demographic variables and genotype distributions of TGF-beta1-509C/T polymorphism between ESCC patients and controls were calculated by Pearson's Chi square test. Associations between TGF-beta1 509C/T polymorphism genotypes and ESCC risk were estimated by OR and their 95% CIs computed using unconditional logistic regression model. RESULTS: There was a significant difference of TGF-beta1-509C/T polymorphism genotype distribution between ESCC group and control group (P<0.001). With the CC genotype as reference, the adjusted OR for CT genotype reached to 0.78 (95% CI: 0.65-0.89; P=0.041), and the adjusted OR for TT homozygous carriers was 0.52 (95% CI: 0.33 0.78; P=0.017). The T allele carriage also presented a lower risk for ESCC (adjusted OR=0.43; 95% CI, 0.29-0.71; P=0.009). CONCLUSION: TGF-beta1-509C/T polymorphism may contributes to ESCC susceptibility in Chinese population. PMID- 26379975 TI - Clinical characteristics of patients with malignancies combined with acute kidney injury. AB - OBJECTIVE: To analyze clinical characteristics and prognostic factors of patients with malignancies combined with acute kidney injury (AKI), providing a basis for clinical AKI prevention and prognosis improvement. METHOD: Hospitalized patients in the Central Hospital of Nephrology from January 2008 to December 2013 were screened by electronic medical record system; Statistical analysis formalignant tumor patients associated with AKI was conducted. The clinical features of these patients in 6 years were analyzed and compared, and Logistic regression analysis was used to analyze the risk factors of hospitalized mortality in patients with and malignant tumor and AKI. RESULTS: There were 340 cases of malignancies associated with AKI patients, accounting for 30.0% (340/1133) of AKI patients in the same period. In malignancy patients, hematological malignancies accounted for 12.9% (44/340); non-metastatic solid tumor accounted for 54.7% (186/340); metastatic solid tumor accounted for 32.4% (110/340). In factors leading to AKI, post-renal obstruction [60% (204/340)], nephrotoxic drugs or contrast agents [27.9% (95/340)] and hypovolemia [41/340 (12.1%)] were common in patients with malignant tumors. There was no significant difference in the cause of AKI between early 3 years and later 3 years (P>0.05). Hospital mortality in patients with malignancies associated with AKI was [22.9% (78/340)], with an annually declining trend. Multivariate Logistic regression showed that: multiple etiologies, multiple organ failure, metastatic solid tumor, sepsis, and continuous renal replacement therapy were independent risk factors for hospital mortality. CONCLUSION: AKI is a common complication in patients with malignant tumors, with post-renal obstruction as the most common factors. Hospital mortality in malignant tumor patients associated with AKI was higher, and the prevention of AKI is crucial in clinical. PMID- 26379976 TI - Anesthetic management for craniotomy in a patient with massive cerebellar infarction and severe aortic stenosis: a case report. AB - Severe aortic stenosis combined with coronary heart disease remarkably increases the risk of perioperative morbidity and mortality during noncardiac surgery. Surgery and anesthesia often complicate the perioperative outcome if adequate monitoring and proper care are not taken. Therefore, understanding of the hemodynamic changes and anesthetic implications is an important for successful perioperative outcome. This report described the anesthetic management of a patient with a massive cerebellar infarction who was diagnosed with severe aortic stenosis combined with moderate aortic insufficiency and coronary heart disease and hypertension. He was prepared for aortic valve replacement and coronary bypass operation before massive cerebellar infarction occurred. And he received decompressive craniotomy and external ventricular drainage in the prone position under general anesthesia with endotracheal intubation. PMID- 26379977 TI - Effect of sildenafil on erectile dysfunction and improvement in the quality of sexual life in China: a multi-center study. AB - BACKGROUND: Erectile dysfunction (ED) is a common medical condition in middle aged and elderly men; however, large-scale and multi-center epidemiologic studies about the treatment effects on ED in China are lacking. OBJECTIVE: To elucidate the efficacy and safety of a phosphodiesterase type 5 inhibitor (PDE5-i) in the treatment of men with ED in China. METHODS: Patients clinically diagnosed with ED from 53 andrology centers in 15 metropolitan areas in China who were willing to undergo treatment for ED were enrolled in the study. Each participant received 4 weeks of unique PDE5-i treatment, and completed the following forms (International Index of Erectile Function score 5 [IIEF-5], the Erection Hardness Score [EHS], Self-Esteem and Relationship [SEAR], and SF-36 of Health Related Quality of Life). Pre-and post-treatment data were compared using descriptive analysis. RESULTS: A total of 1956 ED patients were included in this study; 1922 patients provided valid questionnaires for analysis. Four weeks of sildenafil treatment was considered effective and safe. Specifically, the IIEF-5 sores (11.30 +/- 3.7 vs. 20.02 +/- 5.1, P < 0.05), EHS levels (99.1% patients increases to level 3 or 4), and the SEAR scores (32.5 vs. 55.1, P < 0.05) were significantly improved compared to baseline. Sildenafil therapy also significantly improved the satisfaction, enjoyment, and frequency of sexual attempts and sexual activity, as well as physical vigor and mental health scores. CONCLUSION: The present study provides direct evidence regarding the efficacy and safety of sildenafil therapy in a large sample of Chinese men with ED, thus verifying that sildenafil improved the symptoms and quality of sexual life. PMID- 26379978 TI - A bioabsorbable membrane (Seprafilm(r)) may prevent postoperative mediastinal adhesions following mediastinoscopy: an experimental study in rats. AB - INTRODUCTION: The aim of this experimental study was to investigate the anti adhesion property of a bioabsorbable membrane following mediastinoscopy in a rat model. METHODS: The study was conducted in 20 male Sprague-Dawley rats. Mediastinoscopy was performed all of them. Rats were divided into two groups; control group (n=10); mediastinoscopy alone, study group (n=10); mediastinoscopy and sodiumhyaluronate-carboxymethlycellulose film (Seprafilm(r); Genzyme Corporation, Cambridge, Mass. USA). It was used to the mediastinal surface at the end of the surgical procedure in study group. Re-mediastinoscopy was performed after 7 days. Adhesion and vascularity grade description scores were analyzed. The parameters evaluated were presence of polymorhphonucleer leucocyte, macrophage, lymphocyte, fibroblasts, edema, neovascularisation, collagenisation, and foreing body reaction. RESULTS: All the rats survived uneventfully until being sacrificed without any postoperative complications. The mean adhesion score was found to be significantly higher in control group (n=2.5+/-0.5) compared with study group (n=1.0+/-0.1) (P=0.007). Vascularity grade description score was significantly higher in control group (n=2.3+/-0.6) than in study group (n=1.4+/ 0.6) (P=0.009). There were no statistical differences between the groups with regard to edema, lymphocyte and macrophage infiltration, fibroblast proliferation and foreign body reactions (P>0.05). CONCLUSION: The used of Seprafilm(r) during the primary procedure can reduce to the mediastinal adhesions. However, further studies are required to assess the precise impact of the anti-adhesive agents on adhesion. PMID- 26379979 TI - Relationship between body mass index and incidence of breast cancer. AB - OBJECTIVE: To investigate the relationship between body mass index (BMI) and the breast cancer incidence, so as to making contribution to breast cancer screening in high-risk groups, to adjustment from passive medical treatment to active treatment Methods: BMI status of 206 breast cancer patients and that of 210 healthy subjects at different ages were compared and analyzed. RESULTS: The mean BMI was significantly higher in breast cancer patients than in healthy subjects 24.45+/-3.50 vs. 23.80+/-3.10 kg/m(2), t=-2.189, P=0.001. When stratified by age, BMI were significantly higher in >=60 age for breast cancer than that of control group (Z=-3.408, P=0.001) and no significant difference in <60 years old .Logistic regression analysis showed that BMI was a risk factor of breast cancer (OR=1.886, 95% CI: 1.122-3.009). CONCLUSION: BMI have a relationship with the occurrence of breast cancer, especially for >=60 years old. PMID- 26379980 TI - The relationship between mean platelet volume and other platelet indices with testicular artery blood flow and fertility: a preliminary study. AB - OBJECTIVES: To examine the relationship between platelets (PLT) and platelets indices such as mean platelet volume (MPV), platelet distribution width (PDW), and plateletcrit (PCT) as noninvasive biomarkers with testicular artery blood flow and fertility. METHODS: Fifty-seven healthy and fertile men with normal semen values and 52 patients with abnormal semen values were included in the study. The participants' PLT, MPV, PDW and PCT values were analyzed. Four different levels of the testicular artery, peak systolic velocity (PSV), end diastolic velocity (EDV), and resistive index (RI) were measured using color Doppler ultrasound. RESULTS: There was no significant difference in terms of platelet and platelet indices (MPV, PDW and PCT) between the fertile and infertile group. There were no between group differences in the RI values of the testicular- and intra-testicular artery. When all fertile and infertile participants were considered together, there was no statistically significant correlation between the parameters of the testicular artery blood flow (PSV, EDV and RI) and platelet and platelet indices (MPV, PDW and PCT) (P > 0.05). CONCLUSIONS: There is not statistically significant correlation between any of the following parameters: platelets and platelet indices such as MPV, PDW and PCT, RI of the testicular artery, and fertility. PMID- 26379981 TI - Analysis on safety and value of CT-guided percutaneous chemical ablation in treatment of pelvic hypovascular metastasis. AB - OBJECTIVE: To investigate the clinical efficacy of CT-guided percutaneous chemical ablation in treatment of pelvic hypovascular metastasis. METHODS: Based on a retrospective analysis of the clinical data of 78 patients with pelvic hypovascular metastasis, CT-guided percutaneous chemical ablation was used to directly puncture lesions. The emulsion consisting of ultra-liquid iodized oil, anhydrous ethanol and oxaliplatin in the proportion of 1:2:2 was slowly injected to the lesions, which should be filled to the greatest extent. The postoperative follow-up lasted for 2~51 months. RESULTS: After surgery, 23 of these 78 cases were reported with merely residual fibrous cords or calcified shadow or complete recovery, and the lesion volume was reduced by >= 50% in 55 cases compared to that before surgery, indicating a total effective rate of 100% (78/78). The tumor size after treatment was significantly reduced compared to that before treatment [(4.5 +/- 1.9) cm(2) vs (20.6 +/- 10.1) cm(2)], and the difference was statistically significant (P = 0.018). Of 34 patients suffering from pain in perineum, buttocks and/or legs and limited mobility of the lower extremities, eliminated pain were reported in 13 cases and relieved symptoms in 21 cases. No intraoperative and postoperative complications were observed. CONCLUSION: In treatment of pelvic hypovascular metastasis, CT-guided percutaneous chemical ablation proves to be minimally invasive, effective and worthy of clinical promotion. PMID- 26379982 TI - A new diagnostic parameter for patellofemoral pain. AB - PURPOSE: Q-angle measurement procedure have not been well standardised. There is a lack of consensus about subject position and knee flexion angle while measuring the Q-angle. Morover Q-angle value which obtained in a single position is a static value and gives an information about the subject's current position. The aim of this study is to obtain a more significant parameter which includes different postures (supine, standing, sitting) and different knee flexion angles instead of a single Q-angle in a fixed position. At the same time this parameter must be functional and dynamic,not a static value like Q-angle. We named this parameter as DeltaQ. METHODS: Our study was applied on case and control groups. All subjects in both groups were male. Case group was consisted of 14 subjects who had patellofemoral pain. Control group was consisted of 14 subjects who had normal knees and normal lower extremities with no reported knee problems. We obtained 3 different Q-angle values and 3 different DeltaQ values for each subject in both groups. Pearson correlation analysis was used for investigation of continuous variables in normal distribution, Spearman correlation analysis was used in abnormal distribution. t test was used in the comparison of values. Logistic regression analysis(forward conditional mod) was used for detecting of determinants of pain. RESULTS: DeltaQ1s of both groups were found as the only statistical significant predictive value for patellofemoral pain. CONCLUSION: There is not an agreement about a standardised q-angle measurement procedure in the literature. Moreover, present procedures provide information about a single and fixed position. In this situation Q-angles which obtained in these fixed positions are static values. We think that we can overcome these problems with this new value. DeltaQ contains multiple q-angles and gives information about all. Also it is a dynamic value for being oriented to position change. Therefore, DeltaQ is an useful indicator for evaluating patellofemoral pain. PMID- 26379983 TI - A different disease: extrasacrococcygeal pilonidal sinuses etiopathogenesis. AB - Pilonidal sinuses (PS) predominantly affect young male adults, usually occurring in the sacrococcygeal region. However, PS occasionally occurs in other parts of the body, referred to as extrasacrococcygeal pilonidal sinus (ESPS). We herein evaluate ESPS ethiopathogenesis and treatment. Of a total of 949 PS cases treated between 2006 and 2011, 21 were of ESPS (2.2% of the total), which were evaluated retrospectively. The affected regions were the breast (n = 1), scalp (n = 2), sternum (n = 2), abdominal wall (n = 5), neck (n = 2), groin (n = 4), and axilla (n = 5). Lesions of the abdominal wall are rare, but less so than lesions in other regions. PS may mimic hidradenitis suppurativa histologically. To our knowledge, PS of the breast and groin have not previously been reported. Twelve of our patients reported shaving the affected region; we suggest this may have played a role in the disease pathogenesis. PMID- 26379984 TI - Intravitreal ranibizumab therapy for retinal arterial macroaneurysm. AB - AIM: To evaluate the anatomic and functional results of intravitreal ranibizumab injection for treatment of symptomatic retinal arterial macroaneurysm (RAM). MATERIALS AND METHODS: A series of seven patients (seven eyes) who had been diagnosed with symptomatic RAM were assessed by comprehensive ophthalmologic examination, fluorescein angiography (FA), optical coherence tomography (OCT), and indocyanine green angiography (ICGA). All patients were treated by intravitreal ranibizumab injection within one week of diagnosis and retreated upon evidence of persistent serous detachment or hemorrhage involving the macula on OCT. Anatomical recovery was examined by FA, OCT, and ICGA. Best-corrected visual acuity (BCVA) and central macular thickness (CMT) were evaluated using the Snellen chart and optical coherence tomography, respectively, at baseline; at 1, 3, and 6 months; and at the final visit. The BCVA and CMT values at baseline and the final visit were compared using the Wilcoxon signed rank test and determination of logarithm of the minimal angle of resolution (logMAR) of BCVA value. RESULTS: Over a mean follow-up period of 10.86 +/- 5.4 months, significant visual and anatomical recovery was observed, with visual acuity improving by three or more lines in all seven patients. The mean logMAR of BCVA improved from 1.09 +/- 0.60 to 0.16 +/- 0.16 (p = 0.018) and mean CMT decreased from 427.5 +/- 132.4 MUm to 208.7 +/- 23.1 MUm (P = 0.018). No complications were observed with intravitreal ranibizumab injection. CONCLUSION: Intravitreal ranibizumab is an effective therapy for symptomatic RAM, improving BCVA and decreasing CMT. PMID- 26379985 TI - Two cases of matrix-producing carcinoma showing chondromyxoid matrix in cytological specimens. AB - Matrix-producing carcinoma (MPC) is extremely rare. Limited reports have described the cytological aspects of MPC. Herein, we present 2 cases of MPC, both of which showed ring-enhancement on magnetic resonance imaging (MRI) and chondromyxoid matrix on cytological specimens. In these cases, the diagnosis of MPC was preoperatively suspected. Recognizing extracellular matrix as chondromyxoid matrix on the cytological specimen is important in making a distinction between MPC and mucinous carcinoma. They share some features on cytology and MRI (ring-enhancement) but have different prognoses and involve different approaches for obtaining histological specimens for neoadjuvant therapy. The reason for the different approaches for obtaining the histological specimens is that tumor cells usually distribute peripherally in MPC in contrast to the relatively uniform distribution of mucinous carcinoma. Therefore, it would be helpful if the diagnosis of MPC can be suspected by examination of the cytological specimen. PMID- 26379986 TI - Whether inflammatory myofibroblastic tumor of the thigh relapses after surgical excision? AB - As reported previously, the 61-year-old male Chinese patient suffering from the inflammatory myofibroblastic tumor of the right thigh without bone involvement was performed a surgical excision and a local radiotherapy two years ago. However, a moderately soft and painful 200 * 100 mm mass of the posterior thigh, where magnetic resonance imaging (MRI) scans revealed an inhomogeneously hyperintense on T1-weighted imaging (T1WI), T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI), was found forty days after the operation. Two years into follow-up, we intend to judge whether the tumor relapses by regular imaging examination including thoracic computed tomography (CT) scans and local MRI scans of lower extremities. The diagnosis of postoperative cyst is suggested. PMID- 26379987 TI - Digital resection and reconstruction of TMJ synovial chondrosarcoma involving the skull base: report of a case. AB - Synovial chondrosarcoma (SCS) is a very rare malignant cartilaginous tumor. To the best of our knowledge, only three reported studies presented the involvement of the temporomandibular joint (TMJ). Hereby, we present a case of surgical management of a SCS of the TMJ, arising from SC and involving the skull base. The surgical procedure includes digital design, resection guided by digital templates, as well as immediate reconstruction with free iliac bone graft (IBG) and pedicled sternoclavicular joint (SCJ). At 1-year follow-up, the TMJ function and form were improved with no sign of local recurrence or metastasis to bone or other joints. However, its distant metastasis to lung was observed. PMID- 26379988 TI - A late diagnosed case of Spontaneous esophageal perforation in an elderly patient. AB - Spontaneous esophageal perforation, also known as Boerhaave's syndrome, is a rare but potentially life-threatening condition, especially in elderly patients with more complications, speedy development and higher mortality. Successful handling of the disease depends on a timely diagnosis and the appropriate choice of treatment. Unfortunately, late diagnosis is common because of the non-specific clinical presentation. We here present a 72-year-old patient of spontaneous esophageal perforation who complained of chest pain, but sharply deteriorated with septic shock. With a vomiting history and gastrointestinal-genic bacterium identified in the chest fluid, the patient was highly suspected for esophageal perforation, though the oral methylene blue test was negative for three times. The diagnosis was finally established by esophagoscopy on the 10(th) day. The perforation was successfully healed by active conservative management and the patient was discharged home on the 43(rd) day eating normal diet. PMID- 26379989 TI - Giant retroperitoneal schwannoma: a case report. AB - Schwannomas are rare tumors originating from the Schwann sheath of the peripheral or cranial nerves. They are usually benign tumors and in 95% of the cases they originate from the peripheral nerves. Occurrence in the retroperitoneum is rare. We report a case of giant retroperitoneal schwannoma. The patient was a 71-year old female. She was admitted in with the complaints of finding abdominal mass for 8 years and emaciation for 1 year. CT scan showed a 15 cm * 11 cm mass located between the liver and the upper pole of the right kidney. After adequate preparation, the patient underwent surgery. During the procedure, we found a 15 cm * 11 cm * 6 cm mass located between the right liver, right kidney, adrenal gland and vena cava and adhered to them. The pathologic diagnosis was schwannoma. PMID- 26379990 TI - Imaging manifestations of intravascular leiomyoma involving the right atrium: a case report and literature review. AB - The aim of this study is to investigate the imaging features of intravascular leiomyoma (IVL) involving the heart and the imaging techniques in the diagnosis of this disease. The imaging features of contrast-enhanced computed tomography (CT), the clinical data and the pathological data of a case of IVL involving the right atrium were retrospectively analyzed and the literatures were reviewed. A 42-year-old woman was admitted to Jinan Central Hospital with a 7-day history of lower extremity weakness, chest tightness and short breath. Contrast-enhanced CT scanning revealed that there was a mass in the inferior vena cava and right atrium, which was heterogeneously enhanced. There was a gap between the vessel wall and the mass. Spiral CT scanning with multiplanner reformation (MPR) reconstruction revealed the morphology, scope and extension pathways of the tumor clearly. Ultrasonography (US) and magnetic resonance imaging (MRI) also played important roles in the diagnosis and differential diagnosis of IVL. To the patients with a history of uterine fibroids, spiral CT scanning, US and MRI could be used to improve the correct diagnosis rates of IVL before surgery. PMID- 26379991 TI - Aortic dissection in women during the course of pregnancy or puerperium: a report of 11 cases in central south China. AB - We have characterized 11 women diagnosed with aortic dissection during the course pregnancy or puerperium by analysis of 1,271 patients enrolled at the Second Xiangya Hospital in central south university of China from 2010 to 2013. The age of these patients ranged from 22 to 39 years old (30.6 +/- 5.6 years old). Among which, 5 cases were noted secondary to Marfan syndrome. Three patients were diagnosed at the late stage of pregnancy, 6 cases were in the postpartum stage, and 2 cases occurred in the early stage of pregnancy. Six patients were Stanford A-type, 4 patients were Stanford B-type, and the rest one was diagnosed as aorta aneurysm. The major symptom for 9 patients was manifested by chest/back pain, 1 patient was characterized by chest pain along with dyspnea, while the other one was featured by dyspnea only. Five out of 6 A-type patients were undergone surgical treatment, and 3 patients were survived, while the rest 1 patient refused surgical treatment and died soon in a local hospital. All 4 B-type patients were survived after surgical therapy, and the patient with aorta aneurysm was also survived after surgical treatment. Together, our data suggest that pregnancy associated aortic dissection is more common in late pregnancy or puerperium, and Marfan's syndrome is likely the highest risk factor to this special group of patients. A quick and accurate diagnosis along with appropriate surgical treatments would be necessary to save the lives for both mother and baby. PMID- 26379992 TI - A presenting with obstructive jaundice in pulmonary adenocarcinoma: a case report. AB - INTRODUCTION: Obstructive jaundice caused by metastases to the distal common bile duct or the ampulla of Vater is often observed in patients with various advanced cancers; however, metastasis of lung cancer to the ampulla of Vater with subsequent development of jaundice is rare. CASE PRESENTATION: The patient was a 41-year-old Chinese female who presented with apparent jaundice and itching. An enlarged right supraclavicular lymph node was found during physical examination. Laboratory tests revealed significantly elevated bilirubin and aminotransferase. Imaging examinations, including ultrasonography, computed tomography (CT), and magnetic resonance cholangiopancreatography (MRCP) revealed a 3.1*2.5*2 cm mass in the distal common bile duct and the ampulla of Vater. The routine chest x-ray film revealed a 4-cm nodule in the upper lobe of the left lung and further CT scan confirmed the diagnosis of left lung cancer. A biopsy of supraclavicular lymph node was performed and the histopathology showed poorly differentiated adenocarcinoma with cytokeratin-7 (CK-7) and thyroid transcription factor-1 (TTF 1) being positive immunohistochemically. The patient underwent a pylorus preserving pancreaticoduodenectomy and the histology of the resected specimen revealed characteristic of pulmonary adenocarcinoma. Thus, the final diagnosis was periampullary metastasis from pulmonary adenocarcinoma. The patient's postoperative recovery was uneventful and the jaundice was disappeared one month later. A pulmonary lobectomy was followed by chemotherapy with combination of vinorelbine and cisplatin for six cycles. CONCLUSION: Similar situations are bound to occur again in the future and we believe that this report could demonstrate that there is a case for aggressive surgical management in patients with periampullary metastasis from pulmonary adenocarcinoma. PMID- 26379993 TI - Posterior reversible encephalopathy syndrome following paroxysmal nocturnal hemoglobinuria: a case report and literature review. AB - Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired disorder characterized by hemolytic anemia, marrow failure, and a high incidence of life threatening venous thrombosis. It is subject to a considerable variety of complications like intestinal obstruction and visceral embolism. The current study firstly presents a 40-year-old male with a previous diagnosis of PNH who developed posterior reversible encephalopathy syndrome (PRES) during treatment with methylprednisolone. He was referred to our department with headache and two episodes of generalized tonic-clonic seizures. Laboratory examination revealed peripheral blood cytopenias and elevated count of reticulocyte. Brain magnetic resonance imaging (MRI) exhibited abnormal signal in the bilateral parieto occipital lobes with symmetric distribution which confirmed the diagnosis of PRES. After receive treatment of dexamethasone, anti-hypertensive and neurotropic drugs, the patient made a complete clinical recovery; and the abnormal signals of MRI were almost completely absorbed. This case shows that PRES might be a rare complication of PNH. Furthermore, it points out the necessity of rapid diagnosis and treatment of PRES. PMID- 26379994 TI - Acute torsion of wandering spleen in a 17-year-old girl. AB - The acute torsion of wandering spleen is a very rare disease characterized by acute abdominal pain. Without early surgical intervention, wandering spleen can lead to splenic infarction or rupture. However, early clinical diagnosis is very difficult, so imaging modalities play an important role. We present a case of acute abdominal pain due to torsion of the wandering spleen in a 17-year-old girl, diagnosed by computed tomography and effectively managed by splenectomy for splenic infarction. PMID- 26379995 TI - Acute hepatitis induced by a Chinese herbal product Qibao Meiran Wan: a case study. AB - Qibao Meiran Wan is a Chinese herbal product sold as a therapy for tonifying the liver and kidney, dizziness, premature graying of hair, backache, constipation, and night sweats. It is widely available in Chinese pharmacies and drugstores and is sold without prescription. We describe a case of acute liver injury in a 26 year-old Chinese man who developed symptomatic hepatitis 1 month after starting Qibao Meiran Wan. There was no evidence of viral hepatitis, Epstein-Barr virus, cytomegalovirus, autoimmune hepatitis, or Budd-Chiari syndrome. The liver injury slowly resolved over 20 days after discontinuing the herbal product. Herbal toxicity was later confirmed by a liver biopsy. Qibao Meiran Wan contains a mixture of several plants including Polygonum multiflorum, which was previously associated with hepatotoxicity. To our knowledge, this is the first report of hepatotoxicity by Qibao Meiran Wan. Clinicians treating patients with acute hepatitis of unclear etiology should pay attention to the consumption of Qibao Meiran Wan. PMID- 26379996 TI - Prosthetic hip joint infection caused by Rothia dentocariosa. AB - Rothia dentocariosa is an aerobic, pleomorphic, catalase-positive, non-motile, gram-positive bacteria that is a part of the normal flora in the oral cavity and respiratory tract. Although it is a rare cause of systemic infection, it may be observed in immunosuppressed individuals. Here we report the case of an 85-year old man who developed prosthetic joint infection that was caused by R. dentocariosa after hemiarthroplasty. This is the first case report of a prosthetic hip joint infection caused by R. dentocariosa in the literature. PMID- 26379997 TI - Anesthesia management of surgery for sigmoid perforation and acute peritonitis patient following heart transplantation: case report. AB - Here we described a case in which a patient underwent emergency laparotomy for acute peritonitis and sigmoid perforation under general anesthesia with a history of heart transplantation. A good knowledge in the physiology of the transplanted heart is critical for effective and safe general anesthesia. We chose etomidate that have a weaker impact on cardiovascular function plus propofol for induction, and propofol plus cisatracurium for maintenance with intermittently analgesics and vasoactive drugs to facilitate the anesthesia. In addition, fluid input, electrolyte and acid-base balance were well adjusted during the whole procedure. The patient was in good condition after the surgery. In this case report we are aiming to provide some guidance for those scheduled for non-cardiac surgery after heart transplant. PMID- 26379998 TI - A case of de novo autoimmune hepatitis. AB - In this study, we reported a case of de novo autoimmune hepatitis. In this case, liver puncture biopsy was carried out and the result showed autoimmune hepatitis. In this report, we described the characteristics of this patient. PMID- 26379999 TI - Sudden discontinuation and reinstitution of olanzapine-associated atypical neuroleptic malignant syndrome in a patient undergoing lung surgery. AB - Neuroleptic malignant syndrome (NMS) is a potentially life-threatening idiosyncratic reaction generally associated with neuroleptics. NMS is characterized by hyperthermia, extrapyramidal symptoms, elevated creatinine kinase (CK), altered mental state, leukocytosis, and problems with vegetative functions. Due to its lower affinity for dopaminergic receptors and higher affinity for serotonin receptors, olanzapine-associated atypical NMS were less common than typical neuroleptics. Here we report a case of NMS induced by sudden discontinuation and reinstitution of olanzapine in a patient with schizophrenia during perioperative period of lung resection, drawing attention to adverse events occurring with reinstitution of atypical neuroleptics in high-risk patients. PMID- 26380000 TI - Letter to the editor in response to the article "The effect of laser epilation on recurrence and satisfaction in patients with sacrococcygeal pilonidal disease: a prospective randomized controlled trial" by Demircan et al. Int J Clin Exp Med 2015; 8(2): 2929-2933. PMID- 26380001 TI - Efficacy of limited fluid resuscitation in patients with hemorrhagic shock: a meta-analysis. AB - BACKGROUNDS: The objective of this meta-analysis was to evaluate the efficacy of limited fluid resuscitation during active hemorrhage compared with regular fluid resuscitation and provide strong evidences for the improvement of fluid resuscitation strategies in uncontrolled hemorrhagic shock. METHODS: Electronic searches were performed using PubMed, Medline, Embase and CNKI in accordance with pre-set guidelines. Clinical trials and observation studies were included or excluded according to the criteria. The endpoints examined were mortality, hemoglobin (Hb), platelets (PLT), hematocrit (Hct), prothrombin Time (PT), activated partial thromboplastin time (APTT), base excess (BE), blood lactic acid (BLA) and the main complications, such as multiple organ dysfunction syndrome (MODS) and acute Respiratory Distress Syndrome (ARDS). Risk ratios (RR), mean differences (MDs) and 95% confidence intervals (95% Cl) were calculated using fixed/random effect model. RESULTS: The search indentified 11 studies including 1482 subjects. 725 hemorrhagic patients were treated with limited fluid resuscitation while 757 patients undertook regular fluid resuscitation during active hemorrhage. Limited fluid resuscitation had its advantage to reduce the mortality in hemorrhagic shock (RR = 0.67; 95% CI = 0.56-0.81; P < 0.0001) and easily controlled the blood routine index close to normal compared with regular fluid resuscitation (Hb: MD = 13.04; 95% CI = 2.69-23.38; P = 0.01. PLT: MD = 23.16; 95% CI = 6.41-39.91; P = 0.007. Hct: MD = 0.02; 95% CI = 0.02-0.03; P < 0.00001). LFR also had shorter PT and APTT compared with RFR (PT: MD = -2.81; 95% CI = -3.44--2.17; P < 0.00001 and APTT: MD = -5.14; 95% CI = -6.16--4.12; P < 0.00001). As for blood gas analysis, LFR reduced the decrease of BE (MD = 2.48; 95% CI = 1.11-3.85; P = 0.0004) and increase of BLA (MD = -0.65; 95% CI = -0.85- 0.44; P < 0.00001). Besides, LFR may also reduce the occurrence of postoperative complications (MODS: RR= 0.37; 95% CI = 0.21-0.66; P = 0.0008. ARDS: RR = 0.35; 95% CI = 0.21-0.60; P < 0.0001). CONCLUSION: The results provide convincing evidence that support the continued investigation and use of limited fluid resuscitation during active hemorrhage in the trauma setting. PMID- 26380002 TI - Association between coffee consumption and the risk of oral cancer: a meta analysis of observational studies. AB - OBJECTIVE: Quantification of the association between the coffee consumption and risk of oral cancer is still conflicting. Thus, we conducted a meta-analysis to summarize the evidence from epidemiological studies of coffee consumption with the risk of oral cancer. METHODS: Pertinent studies were identified by a search of PubMed and Web of Knowledge to March 2015. The random effect model was used. Sensitivity analysis and publication bias were conducted. RESULTS: Data from 12 studies including 4,037 oral cancer cases and 1,872,231 participants were used in this meta-analysis. Pooled results suggested that highest coffee consumption amount versus lowest amount was significantly associated with the risk of oral cancer [summary relative risk (RR) = 0.694, 95% CI = 0.543-0.886, I(2) = 65.0%]. The association was also significant in Europe [summary RR = 0.571, 95% CI = 0.378-0.863], but not in America. No publication bias was found. CONCLUSIONS: Our analysis suggested that the higher coffee consumption might reduce the risk of oral cancer, especially in Europe. PMID- 26380003 TI - The effect of early external X-ray radiation on arterial restenosis post percutaneous transluminal angioplasty. AB - BACKGROUND: Arterial restenosis after percutaneous transluminal angioplasty (PTA) significantly reduces its therapeutic efficacy in treating lower extremity atherosclerotic occlusive diseases (LEAOD). Early external X-ray external radiation has demonstrated positive effects on restenosis; however, effective dosing and the mechanism(s) underlying its efficacy remain unknown. This study explored the effect of early external X-ray radiation on preventing post-PTA restenosis in an iliac intimal injury model. METHODS: Twenty rabbits underwent iliac intimal injury via PTA and received five different radiation doses: 0 Gy (n = 4), 3 Gy (n = 4), 6 Gy (n = 4), 9 Gy (n = 4), and 12 Gy (n = 4). Four rabbits were used as controls. All subjects were fed a high-fat diet prior to PTA and for an additional four-week period post-PTA and then sacrificed for immunohistochemical and Western blotting analysis. RESULTS: Arterial stenosis was significantly improved post-PTA. Alpha smooth muscle actin (alpha-SMA) expression in the 0 Gy to 9 Gy groups was significantly increased post-PTA. Cytochrome C (Cyt C) expression was significantly increased post-PTA and was positively correlated with radiation intensity. Proliferating cell nuclear antigen (PCNA) expression was significantly increased post-PTA with the 0 Gy group showing significantly higher expression than the 3 Gy group. No significant differences were found in CD34 levels between the groups. CONCLUSIONS: Early external X-ray radiation at 6-24 Gy doses effectively restrained VSMC hyperplasia post-PTA, likely through inducing VSMC apoptosis via mitochondrial Cyt C release. However, this technique did not significantly affect the integrity of the vascular endothelium. Therefore, early external X-ray radiation shows promise in preventing post-PTA restenosis. PMID- 26380004 TI - Controversies regarding T status and N status for non-small cell lung cancer. AB - According to the newest version of NCCN Clinical Practice Guidelines for Non Small Cell Lung Cancer (NSCLC), increasing attentions are paid to the role of nodal status and other high-risk factors, including vascular invasion, wedge resection, tumors > 4 cm, visceral pleural involvement, and incomplete lymph node sampling in the individual clinical treatment. Precise definitions of T status and N status, closely associated with prognosis and treatment, are worth expanding further. However, complexity arises because no unity definition exists regarding individual T and N descriptors. In an attempt to explore the potential prognostic values of the T status and N status, we systematically review relevant literature and found that there still remained some disputes about the definitions and prognosis. The adjacent lobe invasion regarded as T2 or T3 has not been reached consensus yet so far. Lymph node spread patterns are associated with the treatment strategies of NSCLC. This review mainly focus on the role of T status and N status and tried to seek appropriate and individual treatment strategies in NSCLC. PMID- 26380005 TI - Tumor markers CA19-9, CA242 and CEA in the diagnosis of pancreatic cancer: a meta analysis. AB - BACKGROUND: Pancreatic cancer has the worst prognosis and early detection is crucial for improving patient prognosis. Therefore, we performed a meta-analysis to evaluate and compare the sensitivity and specificity of single test of CA19-9, CA242, and CEA, as well as combination test in pancreatic cancer detection. METHODS: We searched PubMed, Embase, Medline, and Wanfang databases for studies that evaluated the diagnostic validity of CA19-9, CA242, and CEA between January 1990 and September 2014. Data were analyzed by Meta-Disc and STATA software. RESULTS: A total of 21 studies including 3497 participants, which fulfilled the inclusion criteria were considered for analysis. The pooled sensitivities for CA19-9, CA242, and CEA were 75.4 (95% CI: 73.4-77.4), 67.8 (95% CI: 65.5-70), and 39.5 (95% CI: 37.3-41.7), respectively. The pooled specificities of CA19-9, CA242, and CEA were 77.6 (95% CI: 75.4-79.7), 83 (95% CI: 81-85), and 81.3 (95% CI: 79.3-83.2), respectively. Parallel combination of CA19-9+CA242 has a higher sensitivity (89, 95% CI: 80-95) without impairing the specificity (75, 95% CI: 67 82). CONCLUSIONS: Our meta-analysis showed that CA242 and CA19-9 have better performance in the diagnosis of pancreatic cancer than CEA. Furthermore, parallel combination test of CA19-9+CA242 could be of better diagnostic value than individual CA242 or CA19-9 test. PMID- 26380006 TI - CDK4/6 inhibitor suppresses gastric cancer with CDKN2A mutation. AB - AIM: Gastric cancer is a major health problem and current treatment lacks lasting effect. Targeted therapy for gastric cancer with specific genetic background is in urgent need. METHODS: We have studied The Cancer Genomic Atlas (TCGA) and The Genomics of Drug Sensitivity in Cancer (GDSC) databases to reveal genes with high frequency of mutation and possible sensitive compound against such gene mutation. In vitro studies were conducted to validate the in silico findings. RESULTS: CDKN2A is frequently mutated in gastric cancer, revealed in TCGA database. CDK4/6 inhibitor PD-0332991 was sensitive in cancer cells with CDKN2A mutation, revealed in GDSC database. In vitro studies showed that PD-0332991 could selectively inhibit proliferation of gastric cancer cell with CDKN2A mutation. PD-0332991 could also inhibit cell invasion, migration, and colony formation of gastric cancer cell with CDKN2A mutation. PD-0332991 induced cell cycle arrest but not apoptosis. PD-0332991 inhibited xenograft gastric cancer mouse model. CONCLUSION: Gastric cancer with CDKN2A mutation is sensitive to CDK4/6 inhibitor. PD-0332991 is a potential therapeutic agent for gastric cancer. PMID- 26380007 TI - Efficacy of high-intensity focused ultrasound ablation for adenomyosis therapy and sexual life quality. AB - OBJECTIVE: The aim of this study was to evaluate the efficacy, safety and sexual life quality outcomes of ultrasound-guided high-intensity focused ultrasound (HIFU) ablations for the treatment of patients with symptomatic adenomyosis and uterine volumes >200 cm(3). METHODS: In our prospective clinical trial 47 patients with uterine volumes >200 cm(3) and symptomatic adenomyosis were treated with single treatment sessions of ultrasound-guided HIFU ablations. Beside uterus and adenomyosis lesion size reductions, outcome measures were symptom severity score (SSS), visual analogue scale (VAS) of dysmenorrhea, female sexual function index (FSFI) scores and the incidence of complications. RESULTS: In all 47 patients, the adenomyosis lesions sizes were significantly reduced 12 months after the interventions (P<0.01). The SSS and dysmenorrhea VAS scores were significantly reduced 12 months after the interventions (P<0.01) and the FSFI scores gradually improved during 12 months after the HIFU ablations (P<0.001). No serious complication occurred. CONCLUSION: Ultrasound-guided HIFU ablation is a safe and effective noninvasive alternative for the treatment of uterine volumes >200 cm(3) with symptomatic adenomyosis. Particularly maintaining the integrity of patients' uteri leads to significant FSFI score improvements, which were essentially reduced before the HIFU treatments. PMID- 26380008 TI - The anti-leukemic effect of carnosic acid combined with adriamycin in a K562/A02/SCID leukemia mouse model. AB - The effects of carnosic acid (CA) were investigated on the acute myeloid leukemia (AML) cell growth in vivo. A NOD/SCID AML mouse model, which was set up by inoculation with K562/A02 cells, was used to study whether tumor growth in vivo can be inhibited by CA combined with adriamycin. After being inoculated with K562/A02 cells, the NOD/SCID mice were expressed positive human mdr1 and bcr/abl genes. This result indicates that the K562/A02/SCID leukemia mouse model is successfully established. The mice treated with CA combined with adriamycin exhibit a significant lower number of leukemia cells (20%) than that of untreated animals (32.5%) (P<0.05), in particular with higher percentages of apoptotic cells than the mice treated by single adriamycin (control) group. The median of 95% CI survival time is 19 (10.0-44.2) and 33 (29.4-36.6) days for the control group and the CA-treated group, respectively. The difference is statistically significant (P<0.05). It is illustrated that the natural compound CA, combined with Adriamycin, has high potential to inhibit the growth of malignant cells in vivo, and is a promising adjuvant anti-cancer drug. Prospective studies should be conducted to understand the functional mechanism of CA at the molecular level. PMID- 26380009 TI - Spontaneous resolution of idiopathic vitreomacular traction syndrome in a healthy young man. AB - PURPOSE: To report a case of spontaneous resolution of idiopathic vitreomacular traction syndrome developed in a healthy young man. METHOD: To exam the macular region using Optical coherence tomography (OCT). RESULT: OCT examination revealed an incomplete posterior vitreous detachment (PVD) which remains broad vitreous adhesion at the macular area. The foveal thickness increase to 573 MUm. The maximal diameter of the adhesion suggested the broad Vitreomacular traction (VMT) type. The posterior vitreous cortex was revealed as a highly reflective band. After 6 weeks without surgery, the patient reported spontaneous improvement in visual symptoms. OCT revealed a complete PVD without macular traction. The foveal contour restored and the foveal thickness decreased markedly to 213 MUm. CONCLUSION: A comprehensive OCT evaluation of the vitreoretinal interface, including VMT types, concurrent conditions like CME and ERM, should be taken into consideration before surgery. PMID- 26380010 TI - Prevalence and variation of sesamoid bones in the hand: a multi-center radiographic study. AB - There is rare studies with regard to sesamoid bone variations of the hand in addition to its prevalence and distribution. This study aims to assess both the prevalence and variation of sesamoid bones of the hand. A retrospective review of posteroanterior (PA) and oblique radiographs of 436 left and 414 right hands of 850 adult patients obtained from four hospitals was performed. All X-ray films were examined independently for existing sesamoid bones. The presence of sesamoid bones was confirmed if oblique views revealed a small oval bone volar to the metacarpophalangeal (MCP) joint or interphalangeal (IP) joint of the thumb or finger. The X-ray films consistently revealed two sesamoid bones at the MCP joint of the thumb, and 30.4% were identified with variation, which can be classified into three distinct types based upon the number of ossification centers and the shape of fusion lines seen on standard PA and oblique films. The prevalence of sesamoid bones was 60.8% for index finger MCP joint and 59.1% for small finger MCP joint. At the thumb IP joints, sesamoid bones were only seen in 15.9% hands. Two sesamoid bones were rarely seen in other joints of the hand except thumb MCP joints. PMID- 26380011 TI - Acupoint massage nursing conducive to improve curative effect of the obesity patients who are complicated with hypertension and are treated by oral drugs. AB - OBJECTIVE: observe the curative effect of the simple obesity patients who are complicated with hypertension and are treated by oral drugs under the adjuvant treatment of acupoint massage nursing. METHODS: a total of 42 patients, who suffer from simple obesity but are complicated with mild to moderate hypertension, are selected and then randomly divided into an observation group and a control group by the digital table method. Each group consists of 21 patients. The patients in the control group are treated by the normal oral drugs, while those in the observation group are intervened by acupoint massage except the normal oral drug treatment provided for the control group. Respectively test the body fat percentage content, blood fat and blood pressure indicators of the selected patients in the two groups before treatment and after 12 weeks' treatment. RESULTS: after 12 weeks' treatment, systolic blood pressure, diastolic blood pressure and blood fat indicators of the patients in the control group are improved significantly compared with those before treatment, P < 0.05, but their percentage of body fat does not change significantly, P > 0.05; systolic blood pressure, diastolic blood pressure, blood fat and body fat percentage of the patients in the observation group are significantly improved compared with those before treatment and their improvement effect is better than that of the control group, P < 0.05. Moreover, the relapse rate of the patients in the observation group, who have been cured, is also obviously lower than that of the control group. CONCLUSION: as for the simple obesity patients who are complicated with hypertension, if they accept acupoint massage stimulation therapy, assisted with oral drugs for treatment, their curative effect is obviously superior to that of the single drug treatment. PMID- 26380012 TI - Effect of Androctonus bicolor scorpion venom on the activities of serum enzymes in rats. AB - We studied the effects of black fat-tailed scorpion (Androctonus bicolor) venom on the activities of liver enzymes including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), lactate dehydrogenase (LDH) and creatine kinase (CK) in the sera of rats. The animals were subcutaneously injected with a single dose of crude Androctonus bicolor venom (200 MUg/kg bodyweight) and were sacrificed at different time intervals including 30 min, 1 h, 2 h, 4 h, 8 h and 24 h after venom injection. There was no significant change in ALT activity in rats injected with Androctonus bicolor venom. Although Androctonus bicolor venom did not produce any change in serum AST activity until 1 h post-dosing, it significantly decreased this enzyme activity at 2 h onwards. There were significant decreases in ALP activities throughout the study though mild surges in the enzyme activity were observed at 1 h and 8 h post-dosing. There was a continued significant decrease in serum LDH activity until 8 h after Androctonus bicolor venom injection followed by normalization of LDH activity at 24 h. The activities of serum CK and GGT were significantly decreased at all the time points following Androctonus bicolor envenomation in rats. In conclusion, Androctonus bicolor envenomation in rats significantly reduced the activities of serum enzymes including AST, ALP, LDH, CK and GGT. Androctonus bicolor venom induced hypomagnesemia may account for persistently reduced activities of liver enzymes due to the cofactor role of magnesium in enzyme activities. PMID- 26380013 TI - Video-assisted thoracoscopic surgery for non-small-cell lung cancer in elderly patients: a single-center, case-matched study. AB - The incidence of non-small-cell lung cancer among elderly patients has increased; therefore, older patients are increasingly being considered for radical pulmonary resection. However, data regarding the outcome of video-assisted thoracoscopic surgery (VATS) in elderly patients are limited. The aim of this study was to evaluate the safety and feasibility of VATS in elderly patients with non-small cell lung cancer. From January 2008 to January 2014, a total of 78 patients aged >= 70 years (elderly group) undergoing VATS for NSCLC were matched with 78 patients < 70 years (young group) by demographics, tumor characteristics, and details of surgical procedures. The elderly group was characterized by a higher incidence of hypertension (P = 0.001) and diabetes mellitus (P = 0.014), and >= 2 comorbidities (P = 0.009). Intraoperative variables, such as surgical duration blood loss, and transfusion rate, were not notably different between the groups. Postoperative 30-day mortality, 30-day complications, and 30-day major complications were comparable between the groups. The 5-year overall survival rates were 69% in the young group and 64% in the elderly group, respectively (P = 0.258). The 5-year disease-free survival rates were 65% in the young group and 60% in the elderly group, respectively (P = 0.327). Our results clearly demonstrated that VATS for non-small-cell lung cancer could be safely and efficacy performed in elderly patients; thus, advanced age itself should not be regarded as a contraindication for VATS. PMID- 26380014 TI - Platelet to lymphocyte ratio plays an important role in prostate cancer's diagnosis and prognosis. AB - OBJECTIVE: To compare the platelet to lymphocyte ratio (PLR) in normal people, benign prostatic hyperplasia (BPH) patients and prostate cancer (PCA) patients, and to explore the prognostic role of PLR in PCA. METHODS: 155 normal people, 168 BPH patients and 103 PCA patients were enrolled. PCA patients were divided into PLR low value group (PLR<150) and PLR high value group (PLR>=150), and the difference of patients' clinical characteristics between high value group and low value group was comparative studied. RESULTS: The differences of PLR among normal people, BPH patients and PCA patients were statistically significant. In addition, platelet counts, neutrophil counts, PSA level, LDH level, AKP level, CRP level and alkaline phosphatase level were also significantly increased in PLR high value group, while the hemoglobin level was decreased. Besides, serious events such as coma during hospitalization were also more likely to appear in PLR high value group. PCA patients had an average follow-up of 3 years, and a total of 25 cases of patients died, including 11 (16.4%) cases in the PLR low value group, and 14 (38.9%) cases in PLR high value group with. Three years survival rate of patients in high value group was significantly reduced. Additionally, PLR was a possible risk factor associated with mortality, and an independent predictor of all-cause mortality during follow-up. CONCLUSION: PLR is significantly increased in PCA patients, and it is an independent predictor of 3 year mortality in PCA patients. PMID- 26380015 TI - Elevated expression of E-cadherin in primary breast cancer and its corresponding metastatic lymph node. AB - AIM: This study was to investigate the E-cadherin expression patterns in primary breast cancers and metastatic lymph node. METHODS: Only lymph nodes which were pathologically identified as metastases were included in this study to pair up the primary tumors. E-cadherin RNA expression levels in invasive ductal breast cancer subjects were detected. E-cadherin gene copies were normalized using beta actin gene copies. ER, PR, cerbB2 expressions in the primary tumor were routinely examined by immunohistochemistry method. Tumor characteristics and number of metastatic lymph nodes were gathered from the pathology reports. RESULTS: We tried to explore the relationship between E-cadherin expression in 21 primary tumors and their corresponding metastatic lymph nodes. However, the Q-RT-PCR data show that an aberrant expression existed in both primary tumors and the corresponding lymph nodes (P=0.115), in which metastatic lymph nodes showed slight higher gene copies compared with primary sites (77.77+/-94.74 vs 43.35+/ 40.03, respectively). It is noteworthy that nodal E-cadherin expression was closely but negatively correlated with tumor size (P<0.01, r=-0.775) and number of metastasized lymph nodes (P<0.05, r=-0.519), as tumor size and number of metastasized lymph nodes were already clinically proven to be important prognostic factors. There was no correlation between ER, PR, cerbB2 status in primary tumors and the nodal E-cadherin expression (P>0.05). CONCLUSIONS: It is indicated that E-cadherin expression is aberrant in invasive ductal cancers and their corresponding metastatic lymph nodes. E-cadherin expression in the metastasized lymph node is closely related to tumor size and number of metastasized lymph nodes. PMID- 26380016 TI - miR-23 regulate the pathogenesis of patients with coronary artery disease. AB - OBJECTIVE: To study whether miR-23 is regulated in coronary artery disease (CAD) patients and what is the possible mechanism of miR-23 in regulating CAD progression. Method Three different cohorts (including 13 AMI patients, 176 angina pectoris patients and 127 control subjects) were enrolled to investigate the expression levels of circulating miR-23 in patients with myocardial ischemia and also the relationship between plasma miR-23 and severity of coronary stenosis. Plasma miR-23 levels of participants were examined by real-time quantitative PCR. We further detected the correlation of miR-23 and VEGF by molecular and animal assays. Result miR-23 was enriched in not only diseased endothelial progenitor cells (EPCs) but also the plasma of CAD patients. Besides, we found out miR-23 was able to suppress VEGF expression and EPC activities. Reporter assays confirmed the direct binding and repression of miR-23 to the 3' UTR of VEGF mRNA. Knock down of miR-23 not only restored VEGF levels and angiogenic activities of diseased EPCs in vitro, but further promoted blood flow recovery in ischemic limbs of mice. Conclusion Circulating miR-23 may be a new biomarker for CAD and as a potential diagnostic tool. And increased miR-23 level may be used to predict the presence and severity of coronary lesions in CAD patients. PMID- 26380017 TI - Risk factors of failed transradial approach for percutaneous coronary interventions in Chaoshan Chinese: a locally retrospective analysis. AB - BACKGROUND: Transradial approach PCI reduces vascular complications compared with a transfemoral approach (TFA). TRA-PCI failure has been reported in 5-10% of cases. Reported studies showed that age > 75 years, previous CABG, short stature, female sex, and cardiogenic shock were independent predictors of TRA-PCI failure. However, related risk factors and causes of TRA-PCI failure are not well characterized, especially among Asians. OBJECTIVES: To explore the risk factors and causes of transfemoral approach (TRA)-PCI failure in Chaoshan area. METHODS: We retrospectively analyzed our databases for all patients who underwent TRA-PCI from January 2011 to June 2014 in the First Affiliated Hospital of Shantou University Medical College. Univariate and multivariate analyses were performed to determine independent risk factors of TRA-PCI failure and the causes of TRA PCI failure. RESULTS: A total of 1,276 patients underwent TRA-PCI. From univariate analyses, patients in the TRA-PCI failure group were significantly in women, and more likely to be age > 75 years compared with TRA-PCI success group. Besides, patients in the TRA-PCI failure group were significantly more likely to suffer from left main coronary disease, more heparin dose, longer fluoroscopy time, and more PCI procedural failure compared with the TRA-PCI successful group. From multivariate analysis, female and age > 75 years were independent predictors of TRA-PCI failure. The causes of TRA-PCI failure included unsuccessful radial artery puncture in 34, vascular anomaly in 54, and the problems of guide catheter and guide wire in 26 patients. CONCLUSIONS: Being female and age > 75 years were independent risk factors of TRA-PCI failure. TRA-PCI failures indicated more possibility to suffer from left main coronary disease. The causes of TRA-PCI failure were complicated, among of those vascular abnormalities was an important factor. PMID- 26380018 TI - Rapid prototyping for tissue-engineered bone scaffold by 3D printing and biocompatibility study. AB - The prototyping of tissue-engineered bone scaffold (calcined goat spongy bone biphasic ceramic composite/PVA gel) by 3D printing was performed, and the biocompatibility of the fabricated bone scaffold was studied. Pre-designed STL file was imported into the GXYZ303010-XYLE 3D printing system, and the tissue engineered bone scaffold was fabricated by 3D printing using gel extrusion. Rabbit bone marrow stromal cells (BMSCs) were cultured in vitro and then inoculated to the sterilized bone scaffold obtained by 3D printing. The growth of rabbit BMSCs on the bone scaffold was observed under the scanning electron microscope (SEM). The effect of the tissue-engineered bone scaffold on the proliferation and differentiation of rabbit BMSCs using MTT assay. Universal testing machine was adopted to test the tensile strength of the bone scaffold. The leachate of the bone scaffold was prepared and injected into the New Zealand rabbits. Cytotoxicity test, acute toxicity test, pyrogenic test and intracutaneous stimulation test were performed to assess the biocompatibility of the bone scaffold. Bone scaffold manufactured by 3D printing had uniform pore size with the porosity of about 68.3%. The pores were well interconnected, and the bone scaffold showed excellent mechanical property. Rabbit BMSCs grew and proliferated on the surface of the bone scaffold after adherence. MTT assay indicated that the proliferation and differentiation of rabbit BMSCs on the bone scaffold did not differ significantly from that of the cells in the control. In vivo experiments proved that the bone scaffold fabricated by 3D printing had no acute toxicity, pyrogenic reaction or stimulation. Bone scaffold manufactured by 3D printing allows the rabbit BMSCs to adhere, grow and proliferate and exhibits excellent biomechanical property and high biocompatibility. 3D printing has a good application prospect in the prototyping of tissue-engineered bone scaffold. PMID- 26380019 TI - Quantitative analysis of suspicious thyroid nodules by contrast-enhanced ultrasonography. AB - OBJECTIVE: This study aimed to investigate the characteristics of suspicious thyroid nodules of different pathological types on contrast-enhanced ultrasound (CEUS) with quantitative analysis software (Qlab). METHODS: A total of 101 suspicious thyroid nodules were recruited from 90 adult patients undergoing ultrasound (US), CEUS and fine-needle aspiration cytology (FNCA). The CEUS characteristics were quantitatively analyzed by investigators blind to the pathological information. RESULTS: In 68 benign thyroid nodules, the proportion of single nodules was higher (54.4%) than that of miliary nodules (n = 2-4), and most of them were identical-in, slow-out and hypoenhancement as compared to adjacent normal tissues. In 17 malignant thyroid nodules, most of them were slow in, identical-out and more hypoenhancement as compared to adjacent normal tissues on CEUS. CONCLUSION: Benign thyroid nodules show identical-in, slow-out and hypoenhancement while malignant thyroid nodules have slow-in, identical-out and more hypoenhancement as compared to adjacent normal tissues on CEUS. Quantitative analysis of thyroid nodules on CEUS may help to identify suspicious nodules and select a proper treatment. PMID- 26380021 TI - Association of atrial fibrillation with gene polymorphisms of connexin 40 and angiotensin II receptor type 1 in Chongming adults of Shanghai. AB - OBJECTIVE: To characterized the gene polymorphisms of connexin 40 (cx40) and angiotensin II receptor type 1 (AT1R) in Chongming adults with atrial fibrillation (AF) and to explore their relationships with AF. METHODS: 82 patients with AF, and 82 subjects without AF were enrolled. Polymorphisms of cx40 G-44A and AT1 A1166C were detected. Moreover, several samples were randomly selected to validate the gene polymorphisms of cx40 and AT1. RESULTS: Genotypes AA, AG and GG of cx40 G-44A were found in both AF patients and controls. The frequencies of genotypes AA, AG and GG were 39%, 29% and 32%, respectively, in AF patients and 31%, 35% and 34%, respectively in controls. The frequencies of alleles A and G were 54% and 46%, respectively in AF patients and 48% and 52%, respectively, in controls (P < 0.05). The risk for AF in patients with allele A increased 1.31 times (OR = 1.31, P < 0.05). The frequencies of genotypes AA, AC and CC were 88%, 8% and 4%, respectively in AF patients and 93%, 6% and 1%, respectively in controls. The frequencies of alleles A and C were 92% and 8%, respectively in AF patients and 96% and 4%, respectively in controls (P < 0.05). More AF patients had allele C as compared to controls. The risk for AF increased by 1.43 times in patients with allele C (OR = 1.43, P < 0.05). CONCLUSION: There were relationships between gene polymorphisms of cx40 and AT1 and AF in Chongming adults. Allele A of cx40 G-44A and allele C of AT1 A1166C significantly increase the risk for AF. PMID- 26380020 TI - Caspofungin as secondary antifungal prophylaxis and subsequent maintenance antifungal prophylaxis therapy in hematological malignancy patients. AB - AIM: This study aimed to investigate the efficacy and safety of caspofungin as secondary antifungal prophylaxis (SAP) and subsequent maintenance therapy for SAP in hematological malignancy patients. METHODS: Forty four patients receiving caspofungin for SAP and 43 patients not receiving any SAP agents during their subsequent chemotherapy or HSCT were reviewed retrospectively. The clinical characteristics and diagnosis were analyzed according to the diagnostic criteria for IFD. RESULTS: The recurrence rate of IFD in 44 patients with caspofungin for SAP was 9.1% (4/44), which was much lower than that in 43 patients without SAP (9.1% vs 46.5%, P = 0.000). Patients with SAP had lower recurrent IFD-related mortality than that without SAP (12.5% vs 55.6%, P = 0.131). Among the 44 patients with SAP, caspofungin continued as maintenance antifungal prophylaxis therapy in 18 patients after neutropenia and oral medication became possible, while voriconazole in 14 patients and itraconazole in 12 patients. The recurrent IFD occurred in 2, 1, 1 patient respectively. There was no statistical difference in recurrence rates among different maintenance antifungal prophylaxis therapies (P = 0.922). No severe adverse events were observed during SAP treatment. CONCLUSIONS: Caspofungin is effective and safe to prevent IFD recurrence in hematological malignancy patients undergoing chemotherapy or HSCT. A subsequent maintenance antifungal prophylaxis therapy of oral voriconazole or itraconazole instead of caspofungin after caspofungin as SAP during neutropenia is as effective as caspofungin given constantly. PMID- 26380022 TI - Selective serotonin reuptake inhibitor combined with dengzhanshengmai capsule improves the fatigue symptoms: a 12-week open-label pilot study. AB - OBJECTIVE: This study was to assess the efficacy and safety of selective serotonin reuptake inhibitor (SSRI) plus Dengzhanshengmai capsule in patients with chronic fatigue syndrome (CFS). METHODS: SSRI at a moderate dose plus Dengzhanshengmai (n = 134) with SSRI alone (n = 134) were compared for the efficacy and safety in the treatment of CFS. The therapeutic efficacy and safety were evaluated. RESULTS: As compared to monotherapy group, the efficacy in combined therapy group was better and characterized by the improvement of general fatigue (0.8+/-0.6 vs. 1.3+/-0.7), physical fatigue (0.6+/-0.3 vs. 1.0+/-0.4) and reduced activity (1.0+/-0.5 vs. 1.3+/-0.6) since the 2nd week (P<0.01) and in reduced motivation (2.1+/-0.8 vs. 2.4+/-1.0) since the 8th week (P<0.01) and the improvement continued thereafter. The mental fatigue score and HAD score were comparable between two groups (P>0.05). No significant difference was found in the drop-out rate between SSRI group (15.7%) and SSRI plus Dengzhanshengmai group (18.0%). The reasons for drop out were adverse events (7.5% vs. 9.7%), requests of the patients or career requirement (3.7% vs. 4.5%), loss to follow-up and others (2.2% vs. 3.0%) and lack of efficacy (2.2% vs. 0.7%). Although the patients in combined therapy group experienced a higher rate of hypertension than (5.8% vs. 1.5%), no significant difference was observed (P = 0.08). CONCLUSION: SSRI combined with Dengzhanshengmai capsule may significantly improve the general fatigue, physical fatigue, reduced activity and reduced motivation of CFS patients as compared to monotherapy with SSRI. Furthermore, this combined therapy is safe and tolerable. PMID- 26380023 TI - Up-regulation of HDAC9 promotes cell proliferation through suppressing p53 transcription in osteosarcoma. AB - Increasing studies have demonstrated that altered expression of histone deacetylases (HDACs) plays a critical role in the tumorigenesis through up regulation or down-regulation of key genes involved in cell proliferation, cell cycle regulation and apoptosis. In the present study, the expression and function of HDAC9 were investigated in osteosarcoma. Quantitative real-time PCR and Western blot analysis found that HDAC9 was up-regulated in osteosarcoma tissues, when compared with that in adjacent normal tissues. In vitro studies further demonstrated that overexpression of HDAC9 in U2OS and MG63 cells promoted cell proliferation and invasion. Using chromatin immunoprecipitation (ChIP) assay, we found that HDAC9 epigenetically repressed p53 transcription through binding to its proximal promoter region. Therefore, our data suggest an important role for HDAC9/p53 regulatory pathway in the osteosarcoma progression. PMID- 26380024 TI - Upregulated lncRNA-UCA1 contributes to progression of lung cancer and is closely related to clinical diagnosis as a predictive biomarker in plasma. AB - OBJECTIVE: Long non-coding RNAs (lncRNAs) have been shown to play an important regulatory roles in cancer biology, and the lncRNA-UCA1 is upregulated in several cancers such as bladder cancer, breast cancer and colorectal cancer, however, the contributions of UCA1 to non-small cell lung cancer (NSCLC) remain largely unknown. METHODS: Expression levels of lncRNA-UCA1 in tumor tissues and plasma from NSCLC patients was evaluated by quantitative real-time PCR, and its association with overall survival of patients was analyzed by statistical analysis. Moreover, the UCA1 expression correlation between tumor tissues and plasma was demonstrated by linear regression analysis. RESULTS: the results showed that the expression of UCA1 in NSCLC tissues was obviously higher than that observed in pair-matched adjacent nontumourous tissues, (P < 0.001). The agarose gel electrophoretogram of RT-PCR products further confirmed that UCA1 was increased in NSCLC tissues. To assess the correlation of UCA1 expression with Clinicopathological data, we found that the expression level of UCA1 was associate with histological grade (P < 0.001) and lymph node metastasis (P < 0.001). Intriguingly, the expression of UCA1 was significantly increased in plasma from NSCLC patients. The UCA1 expression measurements obtained from plasma and tumor tissues were strongly correlated in 60 patient samples (r = 0.881). By receiver operating characteristic curve (ROC) analysis, plasma UCA1 provided the highly diagnostic performance for detection of NSCLC (the area under the ROC curve (AUC), 0.886; P < 0.001). In conclusion, the current results indicated that Plasma UCA1 could serve as a potential biomarker for diagnosis of NSCLC. UCA1 as a biomarker in clinical application might significantly improve the efficacy of human NSCLC screening. PMID- 26380025 TI - Efficacy of one- vs. two-stent implantation for coronary bifurcation lesions in diabetic patients utilizing AIR2 as an endpoint. AB - OBJECTIVE: This study aimed to assess the long term outcomes (all-cause death, myocardial infarction, target vessel revascularization, and silent restenosis at 12 months) of one-stent vs. two-stent implantation due to coronary bifurcation lesionsin diabetic patients using AIR2 as a new endpoint. METHODS AND RESULTS: A total of 178 diabetic patients with true coronary bifurcation lesions underwent percutaneous coronary intervention in the DK-Crush trials. All patients were stratified based on the stent placement strategy: one-stent group (n=76) and two stent group (n=102). Results showed the primary endpoint, AIR2, in one-stent group was twice that in two-stent group (32.9% vs. 16.7%, P=0.013). The incidence of silent restenosis at 12 months was also significantly higher in one-stent group (19.7% versus 4.9%, P=0.003). Moreover, Kaplan-Meier analysis revealed the cumulative AIR2-free survival rate after a 12-month follow-up was markedly lower in one-stent group than in two-stent group. Interestingly, MACEs, including death, myocardial infarction and repeat revascularization, were not comparable between 2 groups (13.2% vs. 12.7%, P=0.935). Likewise, the incidence of definite or probable ST in one-stent group was also similar to that in two-stent group (2.6% vs. 4.9%, P=0.761). CONCLUSION: Our study indicates that, in terms of the AIR2 as a combined clinical and angiographic endpoint, two-stent implantation is superior to one-stent implantation for the treatment of coronary bifurcation intervention in diabetic patients. PMID- 26380026 TI - Autophagy involving age-related cognitive behavior and hippocampus injury is modulated by different caloric intake in mice. AB - Recent studies indicated that different caloric intake may influence neuronal function. Excessive caloric intake associated with accelerated aging of the brain and increased the risk of neurodegenerative disorders. And low caloric intake (caloric restriction, CR) could delay aging, and protect the central nervous system from neurodegenerative disorders. The underlying mechanisms remain poorly understood. In this study, thirty six-week-old male C57/BL male mice were randomly divided into three different dietary groups: normal control (NC) group (fed standard diet), CR group (fed low-caloric diet) and high-calorie (HC) group (fed high-caloric diet). After 10 months, spatial memory ability was determined by Morris water maze. Pathological changes of the hippocampus cells were detected with HE and Nissl staining. The expression of proteins involved in autophagy in the hippocampus was determined by immunofluorescence and Western blot. The result of Morris water maze showed that the learning and memory capacity significantly increased in the CR group, and significantly decreased in the HC group. HE and Nissl staining showed cells damaged obviously in the HC group. The expression of mTOR and p62 was increased in the HC group, and decreased in the CR group. The expression of Beclin1, LC3 and cathepsin B was decreased in the HC group, and increased in the CR group. Our findings demonstrate that long-term high caloric intake is a risk factor that can significantly contribute to the development of neurological disease via suppressing autophagy, and CR may prevent age-related learning ability impairment via activating autophagy in mice. PMID- 26380028 TI - Role of microRNAs in diagnosis and treatment of the pathogenesis of gastric cancer [Retraction]. AB - [This retracts the article on p. 5947 in vol. 7, PMID: 25664140.]. PMID- 26380027 TI - Refractive status and optical components of premature babies with or without retinopathy of prematurity at 3-4 years old. AB - PURPOSE: To investigate the refractive status and optical components of premature babies with or without retinopathy of prematurity (ROP) at 3-4 years old, and to explore the influence of prematurity and ROP on the refractive status and optical components. METHODS: Premature babies receiving fundus examination were recruited into ROP group and non-ROP group, with age-matched full-term babies as controls. RESULTS: The incidence of myopia was the highest in ROP (3/59, 5.08%). The incidence of astigmatism was significantly different between ROP (37.29%, 22/59) and controls (17.86%, 15/84). The corneal refractive power in ROP and non-ROP was more potent compared with controls (P<0.05); corneal curvature was steeper (P<0.05); lens thickness was thinner (P<0.05); ocular axial length was shorter P<0.05). The gestational age was negatively related to corneal astigmatism and astigmatism, positively associated with vitreous thickness and axial length. The birth-weight was negatively associated with corneal astigmatism, astigmatism and corneal refractive power, positively related to corneal radius of curvature, vitreous thickness and ocular axial length. CONCLUSION: Premature babies with or without ROP are susceptible to myopia and astigmatism. ROP, prematurity and low birth-weight synergistically influence the development of refractive status and optical components, of which the prematurity and low birth-weight are more important. PMID- 26380029 TI - Ahead of the Curve. PMID- 26380031 TI - Guiding Employer Management of Specialty Drugs. PMID- 26380030 TI - Trends in Medicare Part D Medication Therapy Management Eligibility Criteria. AB - BACKGROUND: To increase the enrollment rate of medication therapy management (MTM) programs in Medicare Part D plans, the US Centers for Medicare & Medicaid Services (CMS) lowered the allowable eligibility thresholds based on the number of chronic diseases and Part D drugs for Medicare Part D plans for 2010 and after. However, an increase in MTM enrollment rates has not been realized. OBJECTIVES: To describe trends in MTM eligibility thresholds used by Medicare Part D plans and to identify patterns that may hinder enrollment in MTM programs. METHODS: This study analyzed data extracted from the Medicare Part D MTM Programs Fact Sheets (2008-2014). The annual percentages of utilizing each threshold value of the number of chronic diseases and Part D drugs, as well as other aspects of MTM enrollment practices, were analyzed among Medicare MTM programs that were established by Medicare Part D plans. RESULTS: For 2010 and after, increased proportions of Medicare Part D plans set their eligibility thresholds at the maximum numbers allowable. For example, in 2008, 48.7% of Medicare Part D plans (N = 347:712) opened MTM enrollment to Medicare beneficiaries with only 2 chronic disease states (specific diseases varied between plans), whereas the other half restricted enrollment to patients with a minimum of 3 to 5 chronic disease states. After 2010, only approximately 20% of plans opened their MTM enrollment to patients with 2 chronic disease states, with the remaining 80% restricting enrollment to patients with 3 or more chronic diseases. CONCLUSION: The policy change by CMS for 2010 and after is associated with increased proportions of plans setting their MTM eligibility thresholds at the maximum numbers allowable. Changes to the eligibility thresholds by Medicare Part D plans might have acted as a barrier for increased MTM enrollment. Thus, CMS may need to identify alternative strategies to increase MTM enrollment in Medicare plans. PMID- 26380033 TI - US Healthcare Annual Spending Estimated to Rise by 5.8% on Average Through 2024. PMID- 26380032 TI - Value-Based Benefit Design to Improve Medication Adherence for Employees with Anxiety or Depression. AB - BACKGROUND: Through reduced out-of-pocket costs and wellness offerings, value based benefit design (VBBD) is a promising strategy to improve medication adherence and other health-related outcomes across populations. There is limited evidence, however, of the effectiveness of these policy-level changes among individuals with anxiety or depression. OBJECTIVES: To assess the impact of a multifaceted VBBD policy that incorporates waived copayments, wellness offerings, and on-site services on medication adherence among plan members with anxiety or depression, and to explore how this intervention and its resulting improved adherence affects other health-related outcomes. METHODS: A retrospective longitudinal pre/post design was utilized to measure outcomes before and after the VBBD policy change. Repeated measures statistical regression models with correlated error terms were utilized to evaluate outcomes among employees of a self-insured global health company and their spouses (N = 529) who had anxiety or depression after the VBBD policy change. A multivariable linear regression model was chosen as the best fit to evaluate a change in medication possession ratio (MPR) after comparing parameters for several distributions. The repeated measures multivariable regression models were adjusted for baseline MPR and potential confounders, including continuous age, sex, continuous modified Charlson Comorbidity Index, and the continuous number of prescriptions filled that year. The outcomes were assessed for the 1 year before the policy change (January 1, 2011, through December 31, 2011) and for 2 years after the change (January 1, 2012, through December 31, 2013). The primary outcome was a change in MPR. The secondary outcomes included healthcare utilization, medical or pharmacy costs, the initiation of medication, generic medication use, and employee absenteeism (the total number of sick days). RESULTS: The implementation of the VBBD strategy was associated with a significant increase in average MPR (0.65 vs 0.61 in the pre-VBBD period; P = .004), the initiation of new medications for anxiety or depression (31.4% vs 29.5%, respectively; P = .033), and the filling of generic medications for anxiety or depression (85.1% vs 80.5%, respectively; P <.001). A multivariable adjusted analysis revealed a 0.05 increase in MPR after the benefit enhancement (P = .002). Healthcare utilization, costs, and absenteeism were not statistically different before and after the VBBD policy change. CONCLUSION: The VBBD strategy was associated with improved medication adherence and cost conscious medication use. Future analyses should explore whether these trends persist over time, and if they can further impact healthcare utilization, cost, and absenteeism. PMID- 26380034 TI - Resource Utilization for Chemotherapy-Induced Nausea and Vomiting Events in Patients with Solid Tumors Treated with Antiemetic Regimens. AB - BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) can lead to increased emergency department visits and hospitalizations, which may contribute to increased cost of care. Antiemetic agents, such as neurokinin-1 (NK1) receptor antagonists and 5-hydroxytryptamine (5-HT3) receptor antagonists, are prescribed for patients receiving highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC). The current guidelines recommend a 3-drug combination of an NK1 receptor antagonist, a 5-HT3 receptor antagonist, and dexamethasone with HEC regimens and certain MEC regimens. OBJECTIVE: To compare the incidence of CINV and CINV-related resource utilization among patients who receive guideline-adherent HEC and MEC regimens and patients who receive non guideline-adherent regimens. METHODS: In this retrospective, claims-based study, Inovalon's Medical Outcomes Research for Effectiveness and Economics Registry (MORE2 Registry) Research Edition database was used to identify 8089 patients with solid tumors receiving therapy with anthracycline plus cyclophosphamide (AC), cisplatin, or carboplatin from June 2013 to December 2013. The patients were stratified according to the use of an NK1 receptor antagonist regimen. International Classification of Diseases, Ninth Revision, Clinical Modification codes were used to identify CINV events associated with hospital, emergency department, and outpatient office visits among patients in the NK1 receptor antagonist group and the non-NK1 receptor antagonist group. RESULTS: A total of 1059 patients were included in the analysis, of whom 51% (N = 536) used an NK1 receptor antagonist-based regimen and 49% (N = 523) used non-NK1 receptor antagonist therapy. A higher percentage of patients receiving AC (73%) than cisplatin (56%) or carboplatin (23%) received an NK1 receptor antagonist. The incidence rates of total CINV events and CINV-related emergency department visits were lower in the group receiving an NK1 receptor antagonist (44% and 9%, respectively) than in the group receiving a non-NK1 receptor antagonist (50% and 15%, respectively). CONCLUSION: The patients receiving an NK1 receptor antagonists had a lower rate of resource utilization, suggesting that the use of NK1 receptor antagonist-containing regimens according to current national guidelines may reduce healthcare resource utilization, such as CINV-related office, hospital, and emergency department visits for patients receiving highly and moderately emetogenic chemotherapy. PMID- 26380035 TI - Tau-er of Power. PMID- 26380036 TI - New Movement in Neuroscience: A Purpose-Driven Life. PMID- 26380037 TI - High-quality permanent draft genome sequence of Bradyrhizobium sp. Ai1a-2; a microsymbiont of Andira inermis discovered in Costa Rica. AB - Bradyrhizobium sp. Ai1a-2 is is an aerobic, motile, Gram-negative, non-spore forming rod that was isolated from an effective nitrogen fixing root nodule of Andira inermis collected from Tres Piedras in Costa Rica. In this report we describe, for the first time, the genome sequence information and annotation of this legume microsymbiont. The 9,029,266 bp genome has a GC content of 62.56% with 247 contigs arranged into 246 scaffolds. The assembled genome contains 8,482 protein-coding genes and 102 RNA-only encoding genes. This rhizobial genome was sequenced as part of the DOE Joint Genome Institute 2010 Genomic Encyclopedia for Bacteria and Archaea-Root Nodule Bacteria (GEBA-RNB) project proposal. PMID- 26380038 TI - High-quality permanent draft genome sequence of Ensifer meliloti strain 4H41, an effective salt- and drought-tolerant microsymbiont of Phaseolus vulgaris. AB - Ensifer meliloti 4H41 is an aerobic, motile, Gram-negative, non-spore-forming rod that can exist as a soil saprophyte or as a legume microsymbiont of common bean (Phaseolus vulgaris). Strain 4H41 was isolated in 2002 from root nodules of P. vulgaris grown in South Tunisia from the oasis of Rjim-Maatoug. Strain 4H41 is salt- and drought-tolerant and highly effective at fixing nitrogen with P. vulgaris. Here we describe the features of E. meliloti 4H41, together with genome sequence information and its annotation. The 6,795,637 bp high-quality permanent draft genome is arranged into 47 scaffolds of 47 contigs containing 6,350 protein coding genes and 72 RNA-only encoding genes, and is one of the rhizobial genomes sequenced as part of the DOE Joint Genome Institute 2010 Genomic Encyclopedia for Bacteria and Archaea-Root Nodule Bacteria (GEBA-RNB) project proposal. PMID- 26380039 TI - Draft genome sequence of the extremely halophilic archaeon Haladaptatus cibarius type strain D43(T) isolated from fermented seafood. AB - An extremely halophilic archaeon, Haladaptatus cibarius D43(T), was isolated from traditional Korean salt-rich fermented seafood. Strain D43(T) shows the highest 16S rRNA gene sequence similarity (98.7 %) with Haladaptatus litoreus RO1-28(T), is Gram-negative staining, motile, and extremely halophilic. Despite potential industrial applications of extremely halophilic archaea, their genome characteristics remain obscure. Here, we describe the whole genome sequence and annotated features of strain D43(T). The 3,926,724 bp genome includes 4,092 protein-coding and 57 RNA genes (including 6 rRNA and 49 tRNA genes) with an average G + C content of 57.76 %. PMID- 26380040 TI - Permanent draft genome sequence of Acidiphilium sp. JA12-A1. AB - The tenacious association between strains of the heterotrophic alphaproteobacterial genus Acidiphilium and chemolithotrophic iron oxidizing bacteria has long been known. In this context the genome of the heterotroph Acidiphilium sp. JA12-A1, an isolate from an iron oxidizing mixed culture derived from a pilot plant for bioremediation of acid mine drainage, was determined with the aim to reveal metabolic properties that are fundamental for the syntrophic interaction between Acidiphilium sp. JA12-A1 and the co-occurring chemolithoautotrophic iron oxidizer. The genome sequence consists of 4.18 Mbp on 297 contigs and harbors 4015 protein-coding genes and 50 RNA genes. Additionally, the molecular and functional organization of the Acidiphilium sp. JA12-A1 draft genome was compared to those of the close relatives Acidiphilium cryptum JF-5, Acidiphilium multivorum AIU301 and Acidiphilium sp. PM DSM 24941. The comparative genome analysis underlines the close relationship between these strains and the highly similar metabolic potential supports the idea that other Acidiphilium strains play a similar role in various acid mine drainage communities. Nevertheless, in contrast to other closely related strains Acidiphilium sp. JA12 A1 may be able to take up phosphonates as an additional source of phosphor. PMID- 26380041 TI - Negative viscosity can enhance learning of inertial dynamics. AB - We investigated how learning of inertial load manipulation is influenced by movement amplification with negative viscosity. Using a force-feedback device, subjects trained on anisotropic loads (5 orientations) with free movements in one of three conditions (inertia only, negative viscosity only, or combined), prior to common evaluation conditions (prescribed circular pattern with inertia only). Training with Combined-Load resulted in lower error (6.89+/-3.25%) compared to Inertia-Only (8.40+/-4.32%) and Viscosity-Only (8.17+/-4.13%) according to radial deviation analysis (% of trial mean radius). Combined-Load and Inertia-Only groups exhibited similar unexpected no-load trials (8.38+/-4.31% versus 8.91+/ 4.70% of trial mean radius), which suggests comparable low-impedance strategies. These findings are remarkable since negative viscosity, only available during training, evidently enhanced learning when combined with inertia. Modeling analysis suggests that a feedforward after-effect of negative viscosity cannot predict such performance gains. Instead, results from Combined-Load training are consistent with greater feedforward inertia compensation along with a small increase in impedance control. The capability of the nervous system to generalize learning from negative viscosity suggests an intriguing new method for enhancing sensorimotor adaptation. PMID- 26380042 TI - Targeting Kupffer cells in non-alcoholic fatty liver disease/non-alcoholic steatohepatitis: Why and how? AB - Mechanisms for non-alcoholic steatohepatitis (NASH) development are under investigation in an era of increased prevalence of obesity and metabolic syndrome. Previous findings have pointed to the role of adipose tissue, adipose tissue macrophages and their secretory products in the development of a chronic inflammatory status inducing insulin resistance and a higher risk of liver steatosis called non-alcoholic fatty liver disease. The activation of resident macrophages [Kupffer cells (KC)] and the recruitment of blood derived monocytes/macrophages into the diseased liver have now been identified as key elements for disease initiation and progression. Those cells could be activated through gut flora modifications and an altered gut barrier function but also through the internalization of toxic lipid compounds in adjacent hepatocytes or in KC themselves. Due to the role of activated KC in insulin resistance, fibrosis development and inflammation amplification, they became a target in clinical trials. A shift towards an anti-inflammatory KC phenotype through peroxisome proliferator activator-receptordelta agonists, an inhibition of macrophage recruitment through anti-C-C chemokine receptor 2 action and a specific blocking of internalization of toxic lipoxidation or glycation compounds into KC by galectin-3 receptor inhibitors are now under investigation in human NASH. PMID- 26380043 TI - Herbal medicine-related hepatotoxicity. AB - Herbal medicine products represent a common therapeutic approach in the East and are gaining increasing popularity in Western countries. They are unjustifiably considered to be side-effect free; on the contrary, severe toxicity, including catastrophic hepatic injury has been reported in association with their use. Vigilance is required from both physicians and the general public. Physicians should always suspect herbal medicines when evaluating a patient with unexplained liver injury. Regulation standards for herbal products need to be reconsidered, so that the efficacy and safety of these products have been clearly demonstrated before they enter the markets. PMID- 26380044 TI - Chronic hepatitis E: A brief review. AB - Hepatitis E viral infection has traditionally been considered an acute, self limited, water borne disease similar to hepatitis A, endemic to developing countries. However, over the past decade, zoonotic transmission and progression to chronicity in human patients has been identified, resulting in persistently elevated transaminase levels, progressive liver injury and cirrhosis. In addition to liver injury, neurological, renal and rheumatological manifestations have also been reported. Chronic hepatitis E occurs mainly in immunosuppressed individuals such as transplant recipients, human immunodeficiency virus patients with low CD4 counts and in patients with hematological malignancies receiving chemotherapy. Diagnosis is established by persistent elevation of hepatitis E virus RNA in the stool or serum. This population often requires treatment with antiviral agents, particularly ribavirin, as spontaneous clearance with reduction in immunosuppression occurs only in about a third of the patients. The purpose of this review, is to further discuss the clinical presentation, and recent advances in diagnosis, treatment and prophylaxis of chronic hepatitis E. PMID- 26380045 TI - Dendritic cells: The warriors upfront-turned defunct in chronic hepatitis C infection. AB - Hepatitis C virus (HCV) infection causes tremendous morbidity and mortality with over 170 million people infected worldwide. HCV gives rise to a sustained, chronic disease in the majority of infected individuals owing to a failure of the host immune system to clear the virus. In general, an adequate immune response is elicited by an efficient antigen presentation by dendritic cells (DCs), the cells that connect innate and adaptive immune system to generate a specific immune response against a pathogen. However, HCV seems to dysregulate the activity of DCs, making them less proficient antigen presenting cells for the optimal stimulation of virus-specific T cells, hence interfering with an optimal anti viral immune response. There are discordant reports on the functional status of DCs in chronic HCV infection (CHC), from no phenotypic or functional defects to abnormal functions of DCs. Furthermore, the molecular mechanisms behind the impairment of DC function are even so not completely elucidated during CHC. Understanding the mechanisms of immune dysfunction would help in devising strategies for better management of the disease at the immunological level and help to predict the prognosis of the disease in the patients receiving antiviral therapy. In this review, we have discussed the outcomes of the interaction of DCs with HCV and the mechanisms of DC impairment during HCV infection with its adverse effects on the immune response in the infected host. PMID- 26380046 TI - Psychosocial assessment and monitoring in the new era of non-interferon-alpha hepatitis C virus treatments. AB - Chronic hepatitis C virus (HCV) is a global concern. With the 2014 Food and Drug Administration approvals of two direct-acting antiviral (DAA) regimens, ledipasvir/sofosbuvir regimen and the ombitasvir/paritaprevir/ritonavir and dasabuvir regimen, we may now be in the era of all-pill regimens for HCV. Until this development, interferon-alpha along with Ribavirin has remained part of the standard of care for HCV patients. That regimen necessitates psychosocial assessment of factors affecting treatment eligibility, including interferon-alpha related depressive symptoms, confounding psychiatric conditions, and social aspects such as homelessness affecting treatment eligibility. These factors have delayed as much as 70% of otherwise eligible candidates from interferon-based treatment, and have required treating physicians to monitor psychiatric as well as medical side effects throughout treatment. All-pill DAA regimens with the efficaciousness that would preclude reliance upon interferon-alpha or ribavirin have been anticipated for years. Efficacy studies for these recently approved DAA regimens provide evidence to assess the degree that psychosocial assessment and monitoring will be required. With shorter treatment timelines, greatly reduced side effect profiles, and easier regimens, psychosocial contraindications are greatly reduced. However, current or recent psychiatric comorbidity, and drug drug interactions with psychiatric drugs, will require some level of clinical attention. Evidence from these efficacy studies tentatively demonstrate that the era of needing significant psychosocial assessment and monitoring may be at an end, as long as a manageable handful of clinical issues are managed. PMID- 26380047 TI - Assessing cardiovascular risk in hepatitis C: An unmet need. AB - Chronic hepatitis C virus (HCV) is associated with significant morbidity and mortality, as a result of the progression towards cirrhosis and hepatocellular carcinoma. Additionally, HCV seems to be an independent risk factor for cardiovascular diseases (CVD) due to its association with insulin resistance, diabetes and steatosis. HCV infection represents an initial step in the chronic inflammatory cascade, showing a direct role in altering glucose metabolism. After achieving sustained virological response, the incidence of insulin resistance and diabetes dramatically decrease. HCV core protein plays an essential role in promoting insulin resistance and oxidative stress. On the other hand, atherosclerosis is a common disease in which the artery wall thickens due to accumulation of fatty deposits. The main step in the formation of atherosclerotic plaques is the oxidation of low density lipoprotein particles, together with the increased production of proinflammatory markers [tumor necrosis factor-alpha, interleukin (IL)-6, IL-18 or C-reactive protein]. The advent of new direct acting antiviral therapy has dramatically increased the sustained virological response rates of hepatitis C infection. In this scenario, the cardiovascular risk has emerged and represents a major concern after the eradication of the virus. Consequently, the number of studies evaluating this association is growing. Data derived from these studies have demonstrated the strong link between HCV infection and the atherogenic process, showing a higher risk of coronary heart disease, carotid atherosclerosis, peripheral artery disease and, ultimately, CVD related mortality. PMID- 26380048 TI - Alpha-fetoprotein before and after pegylated interferon therapy for predicting hepatocellular carcinoma development. AB - AIM: To investigate factors that accurately predict hepatocellular carcinoma (HCC) development after antiviral therapy in chronic hepatitis C (CHC) patients. METHODS: CHC patients who received pegylated interferon and ribavirin were enrolled in this cohort study that investigated the ability of alpha-fetoprotein (AFP) to predict HCC development after interferon (IFN) therapy. RESULTS: Of 1255 patients enrolled, 665 developed sustained virological response (SVR) during mean follow-up period of 5.4 years. HCC was occurred in 89 patients, and 20 SVR patients were included. Proportional hazard models showed that HCC occurred in SVR patients showing AFP >= 5 ng/mL before therapy and in non-SVR patients showing AFP >= 5 ng/mL before and 1 year after therapy besides older age, and low platelet counts. SVR patients showing AFP >= 5 ng/mL before therapy and no decrease in AFP to < 5 ng/mL 1 year after therapy had significantly higher HCC incidence than non-SVR patients showing AFP >= 5 ng/mL before therapy and decreased AFP (P = 0.043). AFP >= 5 ng/mL before therapy was significantly associated with low platelet counts and high values of alanine aminotransferase (ALT) in stepwise logistic regression analysis. After age, gender, platelet count, and ALT was matched by propensity score, significantly lower HCC incidence was shown in SVR patients showing AFP < 5 ng/mL before therapy than in those showing AFP >= 5 ng/mL. CONCLUSION: The criteria of AFP < 5 ng/mL before and 1 year after IFN therapy is a benefical predictor for HCC development in CHC patients. PMID- 26380049 TI - Liver transplantation in a patient with primary antiphospholipid syndrome and Budd-Chiari syndrome. AB - The antiphospholipid syndrome (APS) is an acquired thrombophilic disorder in which autoantibodies are produced to a variety of phospholipids determinants of cell membranes or phospholipid binding proteins. There are few reports about association between antiphospholipid antibodies and development of Budd-Chiari syndrome (BCS). We report the case of BCS development in young Russian male with primary APS. The patient underwent orthotopic liver transplantation on August 26, 2012. At present time his state is good, the blood flow in the liver restored and its function is not impaired. We report about the first time the successful use of dabigatran etexilate for prolonged anticoagulation therapy in APS patient with BCS. In addition patient is managed with immunosuppressive drugs. PMID- 26380050 TI - Laparoscopic surgery for rectal prolapse and pelvic floor disorders. AB - Pelvic floor disorders are different dysfunctions of gynaecological, urinary or anorectal organs, which can present as incontinence, outlet-obstruction and organ prolapse or as a combination of these symptoms. Pelvic floor disorders affect a substantial amount of people, predominantly women. Transabdominal procedures play a major role in the treatment of these disorders. With the development of new techniques established open procedures are now increasingly performed laparoscopically. Operation techniques consist of various rectopexies with suture, staples or meshes eventually combined with sigmoid resection. The different approaches need to be measured by their operative and functional outcome and their recurrence rates. Although these operations are performed frequently a comparison and evaluation of the different methods is difficult, as most of the used outcome measures in the available studies have not been standardised and data from randomised studies comparing these outcome measures directly are lacking. Therefore evidence based guidelines do not exist. Currently the laparoscopic approach with ventral mesh rectopexy or resection rectopexy is the two most commonly used techniques. Observational and retrospective studies show good functional results, a low rate of complications and a low recurrence rate. As high quality evidence is missing, an individualized approach is recommend for every patient considering age, individual health status and the underlying morphological and functional disorders. PMID- 26380051 TI - Coagulation syndrome: Delayed perforation after colorectal endoscopic treatments. AB - Various procedure-related adverse events related to colonoscopic treatment have been reported. Previous studies on the complications of colonoscopic treatment have focused primarily on perforation or bleeding. Coagulation syndrome (CS), which is synonymous with transmural burn syndrome following endoscopic treatment, is another typical adverse event. CS is the result of electrocoagulation injury to the bowel wall that induces a transmural burn and localized peritonitis resulting in serosal inflammation. CS occurs after polypectomy, endoscopic mucosal resection (EMR), and even endoscopic submucosal dissection (ESD). The occurrence of CS after polypectomy or EMR varies according previous reports; most report an occurrence rate around 1%. However, artificial ulcers after ESD are largely theoretical, and CS following ESD was reported in about 9% of cases, which is higher than that for CS after polypectomy or EMR. Most cases of post polypectomy syndrome (PPS) have an excellent prognosis, and they are managed conservatively with medical therapy. PPS rarely develops into delayed perforation. Delayed perforation is a severe adverse event that often requires emergency surgery. Since few studies have reported on CS and delayed perforation associated with CS, we focused on CS after colonoscopic treatments in this review. Clinicians should consider delayed perforation in CS patients. PMID- 26380052 TI - Treatment modalities for early gastric cancer. AB - Different treatment modalities have been proposed in the treatment of early gastric cancer (EGC). Endoscopic resection (ER) is an established treatment that allows curative treatment, in selected cases. In addition, ER allows for an accurate histological staging, which is crucial when deciding on the best treatment option for EGC. Recently, endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) have become alternatives to surgery in early gastric cancer, mainly in Asian countries. Patients with "standard" criteria can be successfully treated by EMR techniques. Those who meet "expanded" criteria may benefit from treatment by ESD, reducing the need for surgery. Standardized ESD training system is imperative to promulgate effective and safe ESD technique to practices with limited expertise. Although endoscopic resection is an option in patients with EGC, surgical treatment continues to be a widespread therapeutic option worldwide. In this review we tried to point out the treatment modalities for early gastric cancer. PMID- 26380054 TI - Laparoscopic right-sided colonic resection with transluminal colonoscopic specimen extraction. AB - AIM: To study the transcolonic extraction of the proximally resected colonic specimens by colonoscopic assistance at laparoscopic colonic surgery. METHODS: The diagnoses of our patients were Crohn's disease, carcinoid of appendix and adenocarcinoma of cecum. We preferred laparoscopic total mesocolic resections. Colon and terminal ileum were divided with endoscopic staplers. A colonoscope was placed per anal and moved proximally in the colon till to reach the colonic closed end under the laparoscopic guidance. The stump of the colon was opened with laparoscopic scissors. A snare of colonoscope was released and the intraperitoneal complete free colonic specimen was grasped. Specimen was moved in to the colon with the help of the laparoscopic graspers and pulled gently through the large bowel and extracted through the anus. The open end of the colon was closed again and the ileal limb and the colon were anastomosed intracorporeally with a 60-mm laparoscopic stapler. The common enterotomy orifice was closed in two layers with a running intracorporeal suture. RESULTS: There were three patients with laparoscopic right-sided colonic resections and their specimens were intended to remove through the remnant colon by colonoscopy but the procedure failed in one patient (adenocarcinoma) due to a bulky mass and the specimen extraction was converted to transvaginal route. All the patients had prior abdominal surgeries and had related adhesions. The operating times were 210, 300 and 500 min. The lengths of the specimens were 13, 17 and 27 cm. In our cases, there were no superficial or deep surgical site infections or any other complications. The patients were discharged uneventfully within 4-5 d and they were asymptomatic after a mean 7.6 mo follow-up (ranged 4-12). As far as we know, there were only 12 cases reported yet on transcolonic extraction of the proximal colonic specimens by colonoscopic assistance after laparoscopic resections. With our cases, success rate of the overall experience in the literature was 80% (12/15) in selected cases. CONCLUSION: Transcolonic specimen extraction for right sided colonic resection is feasible in selected patients. Both natural orifice surgery and intracorporeal anastomosis avoids mini-laparotomy for specimen extraction or anastomosis. PMID- 26380053 TI - Diagnosis of small intramucosal signet ring cell carcinoma of the stomach by non magnifying narrow-band imaging: A pilot study. AB - AIM: To examine the efficacy of non-magnifying narrow-band imaging (NM-NBI) imaging for small signet ring cell carcinoma (SRC). METHODS: We retrospectively analyzed 14 consecutive small intramucosal SRCs that had been treated with endoscopic submucosal dissection (ESD) and 14 randomly selected whitish gastric ulcer scars (control). The strength and shape of the SRCs and whitish scars by NM NBI and white-light imaging (WLI) were assessed with Image J (NIH, Bethesda). RESULTS: NM-NBI findings of SRC showed a clearly isolated whitish area amid the brown color of the surrounding normal mucosa. The NBI index, which indicates the potency of NBI for visualizing SRC, was significantly higher than the WLI index (P = 0.001), indicating SRC was more clearly identified by NM-NBI. Although the NBI index was not significantly different between SRCs and controls, the circle (C)-index, as an index of circularity of tumor shape, was significantly higher in SRCs (P = 0.001). According to the receiver-operating characteristic analysis, the resulting cut-off value of the circularity index (C-index) for SRC was 0.60 (85.7% sensitivity, 85.7% specificity). Thus a lesion with a C-index >= 0.6 was significantly more likely to be an SRC than a gastric ulcer scar (OR = 36.0; 95%CI: 4.33-299.09; P = 0.0009). CONCLUSION: Small isolated whitish round area by NM-NBI endoscopy is a useful finding of SRCs which is the indication for ESD. PMID- 26380055 TI - Fish oils in parenteral nutrition: Why could these be important for gastrointestinal oncology? AB - By the time a gastroenterology patient is moved to parenteral nutrition, he or she is usually in poor health. All parenteral nutrition formulae contain essential nutrients, avoiding components that could cause an adverse reaction. The lipid component is often provided by a soy extract, containing all the fatty acids considered to be essential in the diet. Several trials have considered parenteral nutrition formulas with added fish oils, high in the long chain omega 3 polyunsaturated fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Given the range of biological functions associated with such compounds, especially in reducing inflammatory symptoms, this move would appear rational. However, while data from such trials are often positive, there has been variability among results. Some of this variability could be caused by environmental contaminants in the fish, and/or oxidation of the lipids because of poor storage. The situation is complicated by a recent report that fish oils may counter the effects of platinum chemotherapy. However, this effect associated with a minor component, hexadeca-4,7,10,13-tetraenoic acid. It is suggested that pure DHA and EPA would be beneficial additions to parenteral nutrition, reducing the probability of carcinogenesis and enhancing rational disease management. However, the jury is still out on fish oils more generally. PMID- 26380057 TI - Proton therapy for pancreatic cancer. AB - Radiotherapy is commonly offered to patients with pancreatic malignancies although its ultimate utility is compromised since the pancreas is surrounded by exquisitely radiosensitive normal tissues, such as the duodenum, stomach, jejunum, liver, and kidneys. Proton radiotherapy can be used to create dose distributions that conform to tumor targets with significant normal tissue sparing. Because of this, protons appear to represent a superior modality for radiotherapy delivery to patients with unresectable tumors and those receiving postoperative radiotherapy. A particularly exciting opportunity for protons also exists for patients with resectable and marginally resectable disease. In this paper, we review the current literature on proton therapy for pancreatic cancer and discuss scenarios wherein the improvement in the therapeutic index with protons may have the potential to change the management paradigm for this malignancy. PMID- 26380058 TI - Intrahepatic therapy for liver-dominant metastatic colorectal cancer. AB - In patients with metastatic colorectal cancer, the liver is the most common site of metastatic disease. In patients with liver-dominant disease, consideration needs to be given to locoregional treatments such as hepatic arterial infusion chemotherapy, transarterial chemoembolisation and selective internal radiation therapy because hepatic metastases are a major cause of liver failure especially in chemorefractory disease. In this review we provide insights on the published literature for locoregional treatment of liver metastases in metastatic colorectal cancer. PMID- 26380056 TI - Adenosquamous carcinoma of the pancreas: Molecular characterization of 23 patients along with a literature review. AB - Adenosquamous carcinoma of the pancreas (ASCP) is a rare entity. Like adenocarcinoma of the pancreas, overall survival is poor. Characteristics of ASCP include central tumor necrosis, along with osteoclasts and hypercalcemia. Various theories exist as to why this histological subtype exists, as normal pancreas tissue has no benign squamous epithelium. Due to the rarity of this disease, limited molecular analysis has been performed, and those reports indicate unique molecular features of ASCP. In this paper, we characterize 23 patients diagnosed with ASCP through molecular profiling using immunohistochemistry staining, fluorescent in situ hybridization, chromogenic in situ hybridization, and gene sequencing, Additionally, we provide a comprehensive literature review of what is known to date of ASCP. Molecular characterization revealed overexpression in MRP1 (80%), MGMT (79%), TOP2A (75), RRM1 (42%), TOPO1 (42%), PTEN (45%), CMET (40%), and C-KIT (10%) among others. One hundred percent of samples tested were positive for KRAS mutations. This analysis shows heretofore unsuspected leads to be considered for treatments of this rare type of exocrine pancreas cancer. Molecular profiling may be appropriate to provide maximum information regarding the patient's tumor. Further work should be pursued to better characterize this disease. PMID- 26380059 TI - Hereditary diffuse gastric cancer: What the clinician should know. AB - Hereditary diffuse gastric cancer (HDGC) is an inherited autosomal dominant syndrome with a penetrance of up to 80% affecting diverse geographic populations. While it has been shown to be caused mainly by germline alterations in the E cadherin gene (CDH1), problematically, the genetic diagnosis remains unknown in up to 60% of patients. Given the important knowledge gaps regarding the syndrome, asymptomatic carriers of CDH1 mutations are advised for a prophylactic total gastrectomy. Intensive annual endoscopic surveillance is the alternative for carriers who decline gastrectomy. As HDGCs have a prolonged indolent phase, this provides a window of opportunity for surveillance and treatment. Recent findings of other gene defects in CTNNA1 and MAP3K6, as well as further characterization of CDH1 mutations and their pathogenicity will change the way HDGC patients are counselled for screening, surveillance and treatment. This review will bring the reader up to date with these changes and discuss future directions for research; namely more accurate risk stratification and surveillance methods to improve clinical care of HDGC patients. PMID- 26380061 TI - Computational pharmacokinetics and in vitro-in vivo correlation of anti-diabetic synergistic phyto-composite blend. AB - Despite tremendous strides in modern medicine stringent control over insulin resistance or restoration of normoglycemia has not yet been achieved. With the growth of molecular biology, omics technologies, docking studies, and in silico pharmacology, modulators of enzymes and receptors affecting the molecular pathogenesis of the disease are being considered as the latest targets for anti diabetic therapy. Therapeutic molecular targets are now being developed basing on the up or down regulation of different signaling pathways affecting the disease. Phytosynergistic anti-diabetic therapy is in vogue both with classical and non classical medicinal systems. However its chemo-profiling, structural and pharmacokinetic validation awaits providing recognition to such formulations for international acceptance. Translational health research with its focus on benchside product development and its sequential transition to patient bedside puts the pharma RDs to a challenge to develop bio-waiver protocols. Pharmacokinetic simulation models and establishment of in vitro-in vivo correlation can help to replace in vivo bioavailability studies and provide means of quality control for scale up and post approval modification. This review attempts to bring different shades highlighting phyto-synergy, molecular targeting of antidiabetic agents via different signaling pathways and bio-waiver studies under a single umbrella. PMID- 26380060 TI - Screening for hepatocellular carcinoma by Egyptian physicians. AB - AIM: To assess the practice of Egyptian physicians in screening patients for hepatocellular carcinoma (HCC). METHODS: The study included 154 physicians from all over Egypt caring for patients at risk for HCC. The study was based on a questionnaire with 20 items. Each questionnaire consisted of two parts: (1) personal information regarding the physician (name, age, specialty and type of health care setting); and (2) professional experience in the care of patients at risk for HCC development (screening, knowledge about the cause and natural course of liver diseases and HCC risk). RESULTS: Sixty-eight percent of doctors with an MD degree, 48% of doctors with a master degree or a diploma and 40% of doctors with a Bachelor of Medicine, Bachelor of Surgery certificate considered the hepatitis C virus (HCV) genotype as risk factor for HCC development (P < 0.05). Ninety percent of physicians specialized in tropical medicine, internal medicine or gastroenterology and 67% of physicians in other specialties advise patients to undergo screening for HCV and hepatitis B virus infection as well as liver cirrhosis (P < 0.05). Eighty-six percent of doctors in University Hospitals and 69% of Ministry of Health (MOH) doctors consider HCV infection as the leading cause of HCC in Egypt (P < 0.05). Seventy-two percent of doctors with an MD degree, 55% of doctors with a master degree or a diploma, 56% of doctors with an MBBCH certificate, 74% of doctors in University Hospitals and 46% of MOH hospital doctors consider abdominal ultrasonography as the most important investigation in HCC screening (P < 0.05). Sixty-five percent of physicians in tropical medicine, internal medicine or gastroenterology and 37% of physicians in other specialties recommend as HCC screening interval of 3 mo (P < 0.05). Seventy-one percent of doctors with an MD degree, 50% of doctors with a master degree or diploma and 60% of doctors with an MBBCH certificate follow the same recommendation. CONCLUSION: In Egypt, physicians specialized in tropical medicine, internal medicine or gastroenterology with an MD degree and working in a University Hospital are best informed about HCC. PMID- 26380063 TI - Initial validation of the Yin-Yang Assessment Questionnaire for persons with diabetes mellitus. AB - AIM: To initially test for the content validity, comprehensibility, test-retest reliability and internal consistency reliability of the Yin-Yang Assessment Questionnaire (YY-AQ). METHODS: The process of initial validity and reliability test covered: (1) content validation from the findings of 18 multiple-case studies, validated Yin- and Yang-deficiency assessment questionnaires, relevant literatures and registered Chinese medicine practitioners; (2) comprehension with the levels of comprehensibility for each item categorized on a 3-point scale (not comprehensible; moderately comprehensible; highly comprehensible). A minimum of three respondents selecting for each item of moderately or highly comprehensible were regarded as comprehensive; (3) test-retest reliability conducted with a 2-wk interval. The intraclass correlation coefficients (ICCs) and their 95%CIs were calculated using a two-way random effects model. Wilcoxon Signed Rank test for related samples was adopted to compare the medians of test-retest scores. An ICC value of 0.85 or higher together with P > 0.05, was considered acceptable; and (4) internal consistency of the total items was measured and evaluated by Cronbach's coefficient alpha (alpha). A Cronbach's alpha of 0.7 or higher was considered to represent good internal consistency. RESULTS: Eighteen Yin deficiency and 14 Yang-deficiency presentation items were finalized from content validation. Five participants with type 2 diabetes mellitus (T2DM) performed the comprehensibility and test-retest reliability tests. Comprehensibility score level of each presentation item was found to be moderate or high in three out of the five participants. Test-retest reliability showed that the single measure ICC of the total Yin-deficiency presentation items was 0.99 (95%CI: 0.89-0.99) and the median scores on the first and 14(th) days were 17 (IQR 6.5-27) and 21 (IQR 6 29) (P = 0.144) respectively. The single measure ICC of the total Yang-deficiency presentation items was 0.88 (95%CI: 0.79-0.99) and the median scores on the first and 14(th) days were 10 (IQR 6-18) and 14 (IQR 7-23) (P = 0.144) respectively. The results of a descriptive correlation study on 140 survey participants with T2DM using the YY-AQ showed that internal consistency of the total Yin-deficiency and Yang-deficiency presentation items was satisfactory, with Cronbach's alpha of 0.79 and 0.78 respectively. CONCLUSION: The YY-AQ will be tested further for comprehensibility, test-retest and internal consistency reliabilities, scoring system validity, construct validity, convergent and discriminant validities, responsiveness and predictive validity. PMID- 26380062 TI - Incretins and selective renal sodium-glucose co-transporter 2 inhibitors in hypertension and coronary heart disease. AB - Hyperglycemia is associated with an increased risk of cardiovascular disease, and the consequences of intensive therapy may depend on the mechanism of the anti diabetic agent(s) used to achieve a tight control. In animal models, stable analogues of glucagon-like peptide-1 (GLP-1) were able to reduce body weight and blood pressure and also had favorable effects on ischemia following coronary reperfusion. In a similar way, dipeptidyl peptidase IV (DPP-IV) showed to have favorable effects in animal models of ischemia/reperfusion. This could be due to the fact that DPP-IV inhibitors were able to prevent the breakdown of GLP-1 and glucose-dependent insulinotropic polypeptide, but they also decreased the degradation of several vasoactive peptides. Preclinical data for GLP-1, its derivatives and inhibitors of the DPP-IV enzyme degradation suggests that these agents may be able to, besides controlling glycaemia, induce cardio-protective and vasodilator effects. Notwithstanding the many favorable cardiovascular effects of GLP-1/incretins reported in different studies, many questions remain unanswered due the limited number of studies in human beings that aim to examine the effects of GLP-1 on cardiovascular endpoints. For this reason, long-term trials searching for positive cardiovascular effects are now in process, such as the CAROLINA and CARMELINA trials, which are supported by small pilot studies performed in humans (and many more animal studies) with incretin-based therapies. On the other hand, selective renal sodium-glucose co-transporter 2 inhibitors were also evaluated in the prevention of cardiovascular outcomes in type 2 diabetes. However, it is quite early to draw conclusions, since data on cardiovascular outcomes and cardiovascular death are limited and long-term studies are still ongoing. In this review, we will analyze the mechanisms underlying the cardiovascular effects of incretins and, at the same time, we will present a critical position about the real value of these compounds in the cardiovascular system and its protection. PMID- 26380064 TI - Visuo-tactile integration in autism: atypical temporal binding may underlie greater reliance on proprioceptive information. AB - BACKGROUND: Evidence indicates that social functioning deficits and sensory sensitivities in autism spectrum disorder (ASD) are related to atypical sensory integration. The exact mechanisms underlying these integration difficulties are unknown; however, two leading accounts are (1) an over-reliance on proprioception and (2) atypical visuo-tactile temporal binding. We directly tested these theories by selectively manipulating proprioceptive alignment and visuo-tactile synchrony to assess the extent that these impact upon body ownership. METHODS: Children with ASD and typically developing controls placed their hand into a multisensory illusion apparatus, which presented two, identical live video images of their own hand in the same plane as their actual hand. One virtual hand was aligned proprioceptively with the actual hand (the veridical hand), and the other was displaced to the left or right. While a brushstroke was applied to the participants' actual (hidden) hand, they observed the two virtual images of their hand also being stroked and were asked to identify their real hand. During brushing, one of three different temporal delays was applied to either the displaced hand or the veridical hand. Thus, only one virtual hand had synchronous visuo-tactile inputs. RESULTS: Results showed that visuo-tactile synchrony overrides incongruent proprioceptive inputs in typically developing children but not in autistic children. Evidence for both temporally extended visuo-tactile binding and a greater reliance on proprioception are discussed. CONCLUSIONS: This is the first study to provide definitive evidence for temporally extended visuo tactile binding in ASD. This may result in reduced processing of amodal inputs (i.e. temporal synchrony) over modal-specific information (i.e. proprioception). This would likely lead to failures in appropriately binding information from related events, which would impact upon sensitivity to sensory stimuli, body representation and social processes such as empathy and imitation. PMID- 26380065 TI - Isolation of adipose and bone marrow mesenchymal stem cells using CD29 and CD90 modifies their capacity for osteogenic and adipogenic differentiation. AB - Mesenchymal stem cells isolated from rats are frequently used for tissue engineering research. However, considerable differences have been identified between rat mesenchymal stem cells and those derived from humans, and no defined panel of markers currently exists for the isolation of these cells. The aim of this study was to examine the effects of cell sorting for CD29(+)/CD90(+) cells from rat adipose and bone marrow tissues on their differentiation and expression of stem cell-associated genes. Flow cytometry showed 66% and 78% CD29(+)/CD90(+) positivity within passage 1 of adipose and bone marrow cultures, respectively. CD29(+)/CD90(+) cells showed a reduction in both osteogenic and adipogenic differentiation when compared with unsorted cells, as determined by alizarin red and Oil Red-O staining, respectively. These findings could not entirely be explained by fluorescence-activated cell sorting-induced cell injury as sort recovery was only modestly affected in adipose-derived cells. Maintaining cells in fluorescence-activated cell sorting buffer did not affect adipose-derived cell viability, but a significant (p < 0.05) reduction was found in bone marrow derived cell viability. Additionally, CD29(+)/CD90(+) selection was associated with a significant decrease in the expression of Lin28, Sox2, Nanog and CD73 in adipose-derived cell cultures, whereas differences in stem cell-associated gene expression were not observed in sorted bone marrow-derived cell cultures. In summary, this study demonstrated that fluorescence-activated cell sorting had differential effects on adipose-derived cells and bone marrow-derived cells, and both CD29(+)/CD90(+) cells displayed a significantly reduced capacity for osteogenic/adipogenic differentiation. In conclusion, we identify that maintaining heterogeneity within the mesenchymal stem cell population may be important for optimal differentiation. PMID- 26380067 TI - Toward the way forward: building an emergency mental health system for Israel. AB - A number of related changes have evolved over the past 25 years: the development of a truly national disaster mental health service in Israel; progress in the science of risk, resilience and evidence base care for those suffering from traumatic stress related disorders; and the development of conceptual models of population level disaster mental health response in the context of emergency management systems such as the Incident Command System. In a recent IJHPR article, Bodas, et al. report on the dynamic history of disaster mental health response in Israel, which informed by the all too numerous real world events affecting the region. What is most striking is that the system now in place reflects true "lessons learned" in that problems and issues identified in incidents informed deliberative planning, and the current system reflects many iterations of "lessons observed and learned". There appears to be commitment across sectors of government in Israel that the mental health consequences of disasters and terrorism are important and a priority. This is advanced thinking and sound policy. As the system in Israel continues to evolve, additional possibilities are offered for further consideration, based on the author's US centric experience, to advance emergency response systems in Israel, the Middle East and around the world. PMID- 26380066 TI - Platelet-rich plasma releasate differently stimulates cellular commitment toward the chondrogenic lineage according to concentration. AB - Platelet-rich plasma has been used to treat articular cartilage defects, with the expectations of anabolic and anti-inflammatory effects. However, its role on cellular chondrogenic or fibrogenic commitment is still a controversy. Herein, the role of platelet-rich plasma releasate, the product obtained following platelet-rich plasma activation, on cellular commitment toward the chondrogenic lineage was evaluated in vitro. Human nasoseptal chondrogenic cells and human bone marrow mesenchymal stromal cells were used as cell types already committed to the chondrogenic lineage and undifferentiated cells, respectively, as different concentrations of platelet-rich plasma releasate were tested in comparison to commonly used fetal bovine serum. Low concentration of platelet rich plasma releasate (2.5%) presented similar effects on cellular growth compared to 10% fetal bovine serum, for both cell types. In a three-dimensional culture system, platelet-rich plasma releasate alone did not induce full nasoseptal chondrogenic cells cartilage-like pellet formation. Nonetheless, platelet-rich plasma releasate played a significant role on cell commitment as high-passage nasoseptal chondrogenic cells only originated cartilage-like pellets when expanded in the presence of platelet-rich plasma releasate rather than fetal bovine serum. Histological analyses and measurements of pellet area demonstrated that even low concentrations of platelet-rich plasma releasate were enough to prevent nasoseptal chondrogenic cells from losing their chondrogenic potential due to in vitro expansion thereby promoting their recommitment. Low concentration of platelet-rich plasma releasate supplemented in chondrogenic medium also increased the chondrogenic potential of mesenchymal stromal cells seeded on collagen-hyaluronic acid scaffolds, as observed by an increase in chondrogenic related gene expression, sulfated glycosaminoglycan production, and compressive modulus following in vitro culture. On the contrary, higher concentration of platelet-rich plasma releasate (10%) hampered some of these features. In conclusion, platelet-rich plasma releasate was able to prevent cellular chondrogenic capacity loss, inducing regain of their phenotype, and modulate cell commitment. Our data support the hypothesis of platelet-rich plasma chondrogenic potential, allowing fetal bovine serum substitution for platelet-rich plasma releasate at specific concentrations in culture medium when chondrogenic commitment is desired on specific cell types and moments of culture. PMID- 26380068 TI - Erratum to: Innate lymphoid cells in asthma phenotypes. AB - [This corrects the article DOI: 10.1186/s13601-015-0068-5.]. PMID- 26380069 TI - The chiropractic profession in Denmark 2010-2014: a descriptive report. AB - BACKGROUND: The chiropractic profession has been well established in Denmark for several decades with state authorization, partial reimbursement by the state and a formal academic education. Biennial systematic data collections among all chiropractors and clinics have been performed since 2010 in order to provide exact information on the profession to The Danish Chiropractic Association (DCA). It is the aim of this study to outline the major characteristics and developments of the chiropractic profession in Denmark to make this information accessible to other stakeholders, domestic as well as foreign. METHODS: Using contact information from the DCA, two questionnaires were distributed electronically to all individual members of the association actively working as chiropractors and all clinics respectively in 2010, 2012 and 2014. The questions asked were developed for this specific survey. RESULTS: Response rates varied between 59 and 78 % for the clinic questionnaires and 75 to 86 % for the individual questionnaires. Almost half the Danish chiropractors were educated in Denmark and a small majority was female. The average Danish chiropractor of 2014 was 44 years old, graduated 17 years earlier, and worked full time in a primary care clinic with at least one colleague. Half the chiropractors spent more than 20 h a year on continued professional development. Danish chiropractic clinics had a median of 3 treatment rooms, most had digital X-ray equipment, around 6 out of 10 had exercise facilities, and 1 out of 4 employed a physiotherapist. Three out of 4 clinics employed a secretary, too. The average duration of a consultation was 40 min for a new patient and 13 min for a follow-up consultation. Virtually all Danish chiropractors working in the primary sector made use of manipulation as one of their treatment modalities. CONCLUSION: This is the first study to describe the state and latest development of the chiropractic profession in Denmark using repeated surveys. Displaying various characteristics of both clinics and individual chiropractors, the image emerging is one of a stable profession where rapid or drastic changes are not taking place over short intervals of time. PMID- 26380070 TI - Case Report: Bone fragment in the third ventricle of a 22 year-old woman. AB - Here we present a very rare case of a woman with a bone fragment in the third ventricle of the brain following compound-depressed skull fractures due to a road traffic accident. There are only few case reports of bullets and textiloma being removed from the third ventricle. Following operative removal of the fragment, the patient was started on cortisol, mineralocorticoid and thyroid hormone replacement. However, the patient eventually died of the severe traumatic hypothalamic insult. PMID- 26380071 TI - A new hypothesis on HIV cure. AB - In this opinion article, I provide the rationale for my hypothesis that nucleoside reverse transcriptase inhibitors (NRTIs) may prevent human immunodeficiency virus (HIV) cure by promoting the survival of cells with integrated provirus. If correct, we may be closer to a cure than we realize. PMID- 26380072 TI - Sevoflurane. AB - Sevoflurane has been available for clinical practice for about 20 years. Nowadays, its pharmacodynamic and pharmacokinetic properties together with its absence of major adverse side effects on the different organ systems have made this drug accepted worldwide as a safe and reliable anesthetic agent for clinical practice in various settings. PMID- 26380073 TI - Advances in understanding cartilage remodeling. AB - Cartilage remodeling is currently among the most popular topics in osteoarthritis research. Remodeling includes removal of the existing cartilage and replacement by neo-cartilage. As a loss of balance between removal and replacement of articular cartilage develops (particularly, the rate of removal surpasses the rate of replacement), joints will begin to degrade. In the last few years, significant progress in molecular understanding of the cartilage remodeling process has been made. In this brief review, we focus on the discussion of some current "controversial" observations in articular cartilage degeneration: (1) the biological effect of transforming growth factor-beta 1 on developing and mature articular cartilages, (2) the question of whether aggrecanase 1 (ADAMTS4) and aggrecanase 2 (ADAMTS5) are key enzymes in articular cartilage destruction, and (3) chondrocytes versus chondron in the development of osteoarthritis. It is hoped that continued discussion and investigation will follow to better clarify these topics. Clarification will be critical for those in search of novel therapeutic targets for the treatment of osteoarthritis. PMID- 26380075 TI - A close look at protein function prediction evaluation protocols. AB - BACKGROUND: The recently held Critical Assessment of Function Annotation challenge (CAFA2) required its participants to submit predictions for a large number of target proteins regardless of whether they have previous annotations or not. This is in contrast to the original CAFA challenge in which participants were asked to submit predictions for proteins with no existing annotations. The CAFA2 task is more realistic, in that it more closely mimics the accumulation of annotations over time. In this study we compare these tasks in terms of their difficulty, and determine whether cross-validation provides a good estimate of performance. RESULTS: The CAFA2 task is a combination of two subtasks: making predictions on annotated proteins and making predictions on previously unannotated proteins. In this study we analyze the performance of several function prediction methods in these two scenarios. Our results show that several methods (structured support vector machine, binary support vector machines and guilt-by-association methods) do not usually achieve the same level of accuracy on these two tasks as that achieved by cross-validation, and that predicting novel annotations for previously annotated proteins is a harder problem than predicting annotations for uncharacterized proteins. We also find that different methods have different performance characteristics in these tasks, and that cross validation is not adequate at estimating performance and ranking methods. CONCLUSIONS: These results have implications for the design of computational experiments in the area of automated function prediction and can provide useful insight for the understanding and design of future CAFA competitions. PMID- 26380074 TI - Engineering food crops to grow in harsh environments. AB - Achieving sustainable agriculture and producing enough food for the increasing global population will require effective strategies to cope with harsh environments such as water and nutrient stress, high temperatures and compacted soils with high impedance that drastically reduce crop yield. Recent advances in the understanding of the molecular, cellular and epigenetic mechanisms that orchestrate plant responses to abiotic stress will serve as the platform to engineer improved crop plants with better designed root system architecture and optimized metabolism to enhance water and nutrients uptake and use efficiency and/or soil penetration. In this review we discuss such advances and how the generated knowledge could be used to integrate effective strategies to engineer crops by gene transfer or genome editing technologies. PMID- 26380076 TI - Metabolome of human gut microbiome is predictive of host dysbiosis. AB - BACKGROUND: Humans live in constant and vital symbiosis with a closely linked bacterial ecosystem called the microbiome, which influences many aspects of human health. When this microbial ecosystem becomes disrupted, the health of the human host can suffer; a condition called dysbiosis. However, the community compositions of human microbiomes also vary dramatically from individual to individual, and over time, making it difficult to uncover the underlying mechanisms linking the microbiome to human health. We propose that a microbiome's interaction with its human host is not necessarily dependent upon the presence or absence of particular bacterial species, but instead is dependent on its community metabolome; an emergent property of the microbiome. RESULTS: Using data from a previously published, longitudinal study of microbiome populations of the human gut, we extrapolated information about microbiome community enzyme profiles and metabolome models. Using machine learning techniques, we demonstrated that the aggregate predicted community enzyme function profiles and modeled metabolomes of a microbiome are more predictive of dysbiosis than either observed microbiome community composition or predicted enzyme function profiles. CONCLUSIONS: Specific enzyme functions and metabolites predictive of dysbiosis provide insights into the molecular mechanisms of microbiome-host interactions. The ability to use machine learning to predict dysbiosis from microbiome community interaction data provides a potentially powerful tool for understanding the links between the human microbiome and human health, pointing to potential microbiome-based diagnostics and therapeutic interventions. PMID- 26380077 TI - The PFP and ESG protein function prediction methods in 2014: effect of database updates and ensemble approaches. AB - BACKGROUND: Functional annotation of novel proteins is one of the central problems in bioinformatics. With the ever-increasing development of genome sequencing technologies, more and more sequence information is becoming available to analyze and annotate. To achieve fast and automatic function annotation, many computational (automated) function prediction (AFP) methods have been developed. To objectively evaluate the performance of such methods on a large scale, community-wide assessment experiments have been conducted. The second round of the Critical Assessment of Function Annotation (CAFA) experiment was held in 2013 2014. Evaluation of participating groups was reported in a special interest group meeting at the Intelligent Systems in Molecular Biology (ISMB) conference in Boston in 2014. Our group participated in both CAFA1 and CAFA2 using multiple, in house AFP methods. Here, we report benchmark results of our methods obtained in the course of preparation for CAFA2 prior to submitting function predictions for CAFA2 targets. RESULTS: For CAFA2, we updated the annotation databases used by our methods, protein function prediction (PFP) and extended similarity group (ESG), and benchmarked their function prediction performances using the original (older) and updated databases. Performance evaluation for PFP with different settings and ESG are discussed. We also developed two ensemble methods that combine function predictions from six independent, sequence-based AFP methods. We further analyzed the performances of our prediction methods by enriching the predictions with prior distribution of gene ontology (GO) terms. Examples of predictions by the ensemble methods are discussed. CONCLUSIONS: Updating the annotation database was successful, improving the Fmax prediction accuracy score for both PFP and ESG. Adding the prior distribution of GO terms did not make much improvement. Both of the ensemble methods we developed improved the average Fmax score over all individual component methods except for ESG. Our benchmark results will not only complement the overall assessment that will be done by the CAFA organizers, but also help elucidate the predictive powers of sequence-based function prediction methods in general. PMID- 26380078 TI - Determination of nonlinear genetic architecture using compressed sensing. AB - BACKGROUND: One of the fundamental problems of modern genomics is to extract the genetic architecture of a complex trait from a data set of individual genotypes and trait values. Establishing this important connection between genotype and phenotype is complicated by the large number of candidate genes, the potentially large number of causal loci, and the likely presence of some nonlinear interactions between different genes. Compressed Sensing methods obtain solutions to under-constrained systems of linear equations. These methods can be applied to the problem of determining the best model relating genotype to phenotype, and generally deliver better performance than simply regressing the phenotype against each genetic variant, one at a time. We introduce a Compressed Sensing method that can reconstruct nonlinear genetic models (i.e., including epistasis, or gene gene interactions) from phenotype-genotype (GWAS) data. Our method uses L1 penalized regression applied to nonlinear functions of the sensing matrix. RESULTS: The computational and data resource requirements for our method are similar to those necessary for reconstruction of linear genetic models (or identification of gene-trait associations), assuming a condition of generalized sparsity, which limits the total number of gene-gene interactions. An example of a sparse nonlinear model is one in which a typical locus interacts with several or even many others, but only a small subset of all possible interactions exist. It seems plausible that most genetic architectures fall in this category. We give theoretical arguments suggesting that the method is nearly optimal in performance, and demonstrate its effectiveness on broad classes of nonlinear genetic models using simulated human genomes and the small amount of currently available real data. A phase transition (i.e., dramatic and qualitative change) in the behavior of the algorithm indicates when sufficient data is available for its successful application. CONCLUSION: Our results indicate that predictive models for many complex traits, including a variety of human disease susceptibilities (e.g., with additive heritability h (2)~0.5), can be extracted from data sets comprised of n ?~100s individuals, where s is the number of distinct causal variants influencing the trait. For example, given a trait controlled by ~10 k loci, roughly a million individuals would be sufficient for application of the method. PMID- 26380079 TI - The molecular epidemiology of incident methicillin-resistant Staphylococcus aureus cases among hospitalized patients in Alberta, Canada: a retrospective cohort study. AB - BACKGROUND: Infection Prevention and Control (IPC) surveillance for incident methicillin-resistant Staphylococcus aureus (MRSA) in hospitalized patients is performed in a complete provincial surveillance network of all acute care facilities in Alberta, Canada. IPC surveillance is centralized using a web-based data entry platform so that each patient is counted only once. All diagnostic laboratories submit the first clinical MRSA isolate associated with a patient without previous MRSA positive clinical cultures in the preceding year to the Provincial Laboratory for Public Health (ProvLab) for molecular typing. This study will investigate the relationship between the IPC epidemiological classification based on time of detection following admission to hospital (Hospital Acquired and Community Associated) and the matched laboratory MRSA surveillance data using a retrospective cohort study design. METHODS: Incident IPC MRSA cases were classified according to IPC epidemiologic definitions. DNA sequencing of the Staphylococcus protein A (spa) gene and pulsed-field gel electrophoresis (PFGE) typing was performed. IPC MRSA surveillance data were matched to the ProvLab molecular surveillance data. Univariate comparisons of proportions were performed for categorical variables and the Student's t test for continuous variables. RESULTS: MRSA molecular typing data were available for matching for 46.7 % (2248/4818) of incident IPC cases. There was agreement in definitions for traditional nosocomial clones (USA100/CMRSA2) with Hospital Acquired (HA)-MRSA (65.1 % of all IPC HA-MRSA) and traditional community clones (USA400/CMRSA7 and USA300/CMRSA10) with Community Acquired (CA)-MRSA (62.4 % of CA-MRSA). However, we observed discordance for both traditional nosocomial/CA MRSA (30.4 % of CA-MRSA) and for traditional community/HA-MRSA (26.9 % of HA MRSA). CONCLUSIONS: We note agreement between traditional nosocomial clones and HA-MRSA, and traditional community clones and CA-MRSA. However, approximately one quarter of HA-MRSA are those of traditional community clones while approximately one-third of CA-MRSA are those of traditional nosocomial clones. Collaborative provincial MRSA surveillance is important as the distinction between IPC case attribution in acute care settings and the historical definitions of MRSA clones as community- or healthcare-associated have blurred. PMID- 26380080 TI - The fracture mechanics of human bone: influence of disease and treatment. AB - Aging and bone diseases are associated with increased fracture risk. It is therefore pertinent to seek an understanding of the origins of such disease related deterioration in bone's mechanical properties. The mechanical integrity of bone derives from its hierarchical structure, which in healthy tissue is able to resist complex physiological loading patterns and tolerate damage. Indeed, the mechanisms through which bone derives its mechanical properties make fracture mechanics an ideal framework to study bone's mechanical resistance, where crack growth resistance curves give a measure of the intrinsic resistance to the initiation of cracks and the extrinsic resistance to the growth of cracks. Recent research on healthy cortical bone has demonstrated how this hierarchical structure can develop intrinsic toughness at the collagen fibril scale mainly through sliding and sacrificial bonding mechanisms that promote plasticity. Furthermore, the bone-matrix structure develops extrinsic toughness at much larger micrometer length-scales, where the structural features are large enough to resist crack growth through crack-tip shielding mechanisms. Although healthy bone tissue can generally resist physiological loading environments, certain conditions such as aging and disease can significantly increase fracture risk. In simple terms, the reduced mechanical integrity originates from alterations to the hierarchical structure. Here, we review how human cortical bone resists fracture in healthy bone and how changes to the bone structure due to aging, osteoporosis, vitamin D deficiency and Paget's disease can affect the mechanical integrity of bone tissue. PMID- 26380081 TI - No effect of exogenous melatonin on development of cryopreserved metaphase II oocytes in mouse. AB - BACKGROUND: This study was conducted to investigate effect of exogenous melatonin on the development of mouse mature oocytes after cryopreservation. RESULTS: First, mouse metaphase II (MII) oocytes were vitrified in the open-pulled straws (OPS). After warming, they were cultured for 1 h in M2 medium containing melatonin at different concentrations (0, 10(-9), 10(-7), 10(-5), 10(-3) mol/L). Then the oocytes were used to detect reactive oxygen species (ROS) and glutathione (GSH) levels (fluorescence microscopy), and the developmental potential after parthenogenetic activation. The experimental results showed that the ROS level and cleavage rate in 10(-3) mol/L melatonin group was significantly lower than that in melatonin-free group (control). The GSH levels and blastocyst rates in all melatonin-treated groups were similar to that in control. Based on the above results, we detected the expression of gene Hsp90aa1, Hsf1, Hspa1b, Nrf2 and Bcl-x1 with qRT-PCR in oocytes treated with 10(-7), or 10(-3) mol/L melatonin and untreated control. After warming and culture for 1 h, the oocytes showed higher Hsp90aa1 expression in 10(-7) mol/L melatonin-treated group than in the control (P < 0.05); the Hsf1, Hsp90aa1 and Bcl-x1 expression were significantly decreased in 10(-3) mol/L melatonin-treated group when compared to the control. Based on the above results and previous research, we detected the development of vitrified-warmed oocytes treated with either 10(-7) or 0 mol/L melatonin by in vitro fertilization. No difference was observed between them. CONCLUSIONS: Our results indicate that the supplementation of melatonin (10(-9) to 10(-3) mol/L) in culture medium and incubation for 1 h did not improve the subsequent developmental potential of vitrified-warmed mouse MII oocytes, even if there were alteration in gene expression. PMID- 26380082 TI - (13)C-labeled biochemical probes for the study of cancer metabolism with dynamic nuclear polarization-enhanced magnetic resonance imaging. AB - In recent years, advances in metabolic imaging have become dependable tools for the diagnosis and treatment assessment in cancer. Dynamic nuclear polarization (DNP) has recently emerged as a promising technology in hyperpolarized (HP) magnetic resonance imaging (MRI) and has reached clinical relevance with the successful visualization of [1-(13)C] pyruvate as a molecular imaging probe in human prostate cancer. This review focuses on introducing representative compounds relevant to metabolism that are characteristic of cancer tissue: aerobic glycolysis and pyruvate metabolism, glutamine addiction and glutamine/glutamate metabolism, and the redox state and ascorbate/dehydroascorbate metabolism. In addition, a brief introduction of probes that can be used to trace necrosis, pH changes, and other pathways relevant to cancer is presented to demonstrate the potential that HP MRI has to revolutionize the use of molecular imaging for diagnosis and assessment of treatments in cancer. PMID- 26380083 TI - Predictors of breast self - examination among female teachers in Ethiopia using health belief model. AB - BACKGROUND: Breast cancer is by far the most frequent cancer of women. It is the second leading cause of death in women worldwide. Approximately one out of eight women develops breast cancer all over the world. Majority of cases of cancer of the breast are detected by women themselves, stressing the importance of breast self-examination. The main objective of this study was to assess predictors of breast self-examination among female teachers in Kafa Zone, South West part of Ethiopia. METHODS: A cross-sectional study was conducted among randomly selected 315 female teachers. Self administered a structured questionnaire including socio demographic characteristics, knowledge about breast cancer and perception of teachers on breast self examination using the Champion's revised Health Belief Model sub scales used as data collection instrument. Multivariable logistic regression analyses were used to identify independent predictors of breast self examination performance. RESULT: Three hundred and fifteen female teachers were participated in this study. Their mean age was 33 SD [+/-7] years. Only 52 (16.5 %) participants ever heard about breast self examination and from those who heard about breast self examination 38 (73.07 %) of them ever performed breast self examination. After controlling for possible confounding factors, the result showed that knowledge towards breast self examination, perceived susceptibility, perceived severity and the net perceived benefit were found to be the major predictors of breast self examination. CONCLUSION: This study revealed that breast self examination performance among female teachers was very low. Therefore, behavior change communication and interventions that emphasize different domains that increase the perceived threat to breast cancer as well as on the benefits of breast self-examination to increase the perception of the teachers in an integrated manner may be the most effective strategies that should be considered by the health offices and educational offices. These may help to increase the knowledge and skill of female teachers on how to perform breast self examination and its importance hence helpful for wider of the community. PMID- 26380084 TI - Venous thromboembolism and lung cancer: a review. AB - Venous thromboembolism (VTE) is a common complication of malignancies and epidemiological studies suggest that lung cancer belonged to the group of malignancies with the highest incidence rates of VTE. Risk factors for VTE in lung cancer patients are adenocarcinoma, NSCLC in comparison with SCLC, advanced disease, pneumonectomy, chemotherapy including antiangiogenic therapy. Other risk factors are pretreatment platelet counts and increased release of TF-positive microparticles. Elevated D-dimer levels do not necessarily indicate an increased risk of VTE but have been shown to be predictive for a worse clinical outcome in lung cancer patients. Mechanisms responsible for the increase in venous thrombosis in patients with lung cancer are not understood. Currently no biomarker is recognized as a predictor for VTE in lung cancer patients. Although several clinical trials have reported the efficacy of antithrombotic prophylaxis in patients with lung cancer who are receiving chemotherapy, further trials are needed to assess the clinical benefit since these patients are at an increased risk of developing a thromboembolism. PMID- 26380085 TI - Perceptions of the causes of eating disorders: a comparison of individuals with and without eating disorders. AB - BACKGROUND: In this study, we examined perceptions regarding the causes of eating disorders, both among those with eating disorders as well as those without. By understanding the differences in perceived causes between the two groups, better educational programs for lay people and those suffering from eating disorders can be developed. METHOD: This study used open-ended questions to assess the beliefs of 57 individuals with self-reported eating disorders and 220 without. Participants responded to the questions, "What do you think was (were) the cause(s) of your eating disorder?" and "What do you think is (are) the cause(s) of eating disorders?". RESULTS: A list of possible codes for the causes of eating disorders was created based on a thorough review of the literature. A manually generated set of eight codes was then created from individuals' actual responses. Frequencies and chi square analyses demonstrated differences in rates of endorsement between those with eating disorders and those without. Participants with eating disorders most frequently endorsed psychological/emotional and social problems, with genetics/biology and media/culture ideals least endorsed. Participants without eating disorders most frequently endorsed psychological/emotional problems and media/culture ideals, with traumatic life events and sports/health least endorsed. There was a difference between groups in the endorsement of the media as a cause of eating disorders, suggesting that those without eating disorders may overly attribute the media as the main cause while those with eating disorders may not be fully aware of the media's impact. Additionally, while both groups highly endorsed psychological/emotional problems, there was a noticeable stigma about eating disorders among those without eating disorders. CONCLUSIONS: There were noteworthy differences between samples; such differences suggest that there is a need for more education on the topic of eating disorders. Furthermore, despite empirical support for the effects of genetics, sports, and family factors, these were infrequently endorsed as causes of eating disorders by both groups. Our results suggest that there is a need for more education regarding the factors associated with eating disorders, in order to reduce the stigma surrounding these disorders and to potentially aid the treatment process. PMID- 26380086 TI - Baseline circulating IL-17 predicts toxicity while TGF-beta1 and IL-10 are prognostic of relapse in ipilimumab neoadjuvant therapy of melanoma. AB - BACKGROUND: We evaluated candidate circulating serum cytokines, chemokines and growth factors in patients with locally/regionally advanced melanoma receiving neoadjuvant ipilimumab with toxicity and clinical outcome. METHODS: Patients were treated with ipilimumab (10 mg/kg IV every 3 weeks, 2 doses) before and after surgery. xMAP multiplex serum testing for 36 functionally selected cytokines and chemokines was performed at baseline and at six weeks (following ipilimumab). Based on our prior data, the association of IL-17 and immune related colitis was tested. Serum cytokines were divided into functional groups (Th1, Th2, Regulatory, Proinflammatory) and were assessed at baseline and week 6 using sparse-group Lasso modeling to assess the association of various cytokine groups with progression free survival (PFS). The linear combination of the cytokines/chemokines in this model was then used as a risk score and a Kaplan Meier curve was generated to examine the association of the dichotomized score and PFS. RESULTS: Thirty-five patients were enrolled whose staging was: IIIB (3; N2b), IIIC (30; N2c, N3), IV (2). Median follow-up was 18 months. Among 33 evaluable patients, median PFS was 11 months (95 % CI = 6.2-19.2). IL-17 was found to correlate significantly with the incidence of grade 3 diarrhea/colitis when measured at baseline (p = 0.02) with a trend towards significance at 6 weeks (p = 0.06). In the modeling analysis, at baseline, the linear combination of 2 regulatory cytokines [TGF- beta1 (rho = 0.19) and IL-10 (rho = -0.34)] was significantly associated with PFS (HR 2.66; p = 0.035). No significant correlations with clinical outcomes were found in examining the week 6 cytokines. CONCLUSIONS: Baseline IL-17 level was significantly associated with the later development of severe diarrhea/colitis while the combination of baseline TGF- beta1 and IL-10 levels were associated with therapeutic clinical outcome after neoadjuvant ipilimumab. These findings warrant further investigation and validation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT00972933. PMID- 26380087 TI - Intrathecal trastuzumab: immunotherapy improves the prognosis of leptomeningeal metastases in HER-2+ breast cancer patient. AB - We describe the clinical and therapeutic course of a 51-year-old woman with HER 2+ breast cancer who developed leptomeningeal (LM) and spinal cord metastases after 8 years of stable disease on combination therapy with intravenous (IV) trastuzumab. Due to progressive CNS disease, intrathecal (IT) trastuzumab was introduced to enhance HER-2+ therapy into the CSF space. A combination HER-2+ targeted approach achieved clinical remission with stable disease in our patient 46 months after she was diagnosed with LM metastases. However, spinal cord C-1 metastasis was not fully controlled with IT trastuzumab, ultimately leading to the patient's respiratory compromise. In our patient, IT trastuzumab immunotherapy improved prognosis and was an effective strategy to manage HER-2+ LM disease. Given alone or alongside other anti-HER-2+ therapeutics with sufficient CNS penetration, IT trastuzumab could extend the lifespan of patients with leptomeningeal and CNS metastases. PMID- 26380088 TI - A new paradigm for tumor immune escape: beta-catenin-driven immune exclusion. AB - Increasing evidence is emerging that immunotherapeutic interventions, including checkpoint blockade, are predominantly effective in patients with a pre-existing T cell-inflamed tumor microenvironment. Understanding the mechanisms leading to a non-T cell-inflamed microenvironment are crucial for the development of novel treatment modalities to expand the fraction of patients benefiting from immunotherapy. Based on the hypothesis that one source of inter-patient heterogeneity would lie at differential activation of specific oncogene pathways within the tumor cells themselves, our group recently observed that tumor-cell intrinsic activation of the WNT/beta-catenin pathway correlates with absence of T cells from the microenvironment in metastatic melanoma. Genetically-engineered mouse models confirmed a causal relationship, via a mechanism of failed Batf3 lineage dendritic cell recruitment. Hence, tumor cell-intrinsic activation of beta-catenin is the first oncogenic pathway demonstrated to exclude the anti tumor immune response, revealing a potential therapeutic target for improving immunotherapy responsiveness. PMID- 26380089 TI - Immune monitoring technology primer: flow and mass cytometry. PMID- 26380091 TI - Fluconazole and acetazolamide in the treatment of ectopic Cushing's syndrome with severe metabolic alkalosis. AB - Cushing's syndrome (CS) due to ectopic ACTH production accounts for about 10% of all types of CS and is frequently associated with metabolic alkalosis. Treatment of CS involves surgical resection and/or medical therapy to control hypercortisolism. We present the case of an 80-year-old woman affected by CS due to an unknown cause. The patient had severe metabolic alkalosis with refractory hypokalemia. To treat the underlying CS, fluconazole was initiated due to unavailability of ketoconazole. In spite of markedly decreasing cortisol levels, metabolic alkalosis persisted. Treatment of metabolic alkalosis with acetazolamide was thus initiated and pH levels successfully lowered. This case report shows that hypercortisolism can be effectively treated with fluconazole in cases where ketoconazole is unavailable or not tolerated and that persistent severe metabolic alkalosis caused by glucocorticoid excess can be safely and successfully treated with acetazolamide. LEARNING POINTS: Hypercortisolism can be effectively treated with fluconazole where ketoconazole is unavailable or not tolerated.Glucocorticoid excess can cause severe metabolic alkalosis.Persistent severe metabolic alkalosis can be safely and successfully treated with acetazolamide. PMID- 26380090 TI - Summing the strokes: energy economy in northern elephant seals during large-scale foraging migrations. AB - BACKGROUND: The energy requirements of free-ranging marine mammals are challenging to measure due to cryptic and far-ranging feeding habits, but are important to quantify given the potential impacts of high-level predators on ecosystems. Given their large body size and carnivorous lifestyle, we would predict that northern elephant seals (Mirounga angustirostris) have elevated field metabolic rates (FMRs) that require high prey intake rates, especially during pregnancy. Disturbance associated with climate change or human activity is predicted to further elevate energy requirements due to an increase in locomotor costs required to accommodate a reduction in prey or time available to forage. In this study, we determined the FMRs, total energy requirements, and energy budgets of adult, female northern elephant seals. We also examined the impact of increased locomotor costs on foraging success in this species. RESULTS: Body size, time spent at sea and reproductive status strongly influenced FMR. During the short foraging migration, FMR averaged 90.1 (SE = 1.7) kJ kg(-1)d(-1) - only 36 % greater than predicted basal metabolic rate. During the long migration, when seals were pregnant, FMRs averaged 69.4 (+/-3.0) kJ kg(-1)d(-1) - values approaching those predicted to be necessary to support basal metabolism in mammals of this size. Low FMRs in pregnant seals were driven by hypometabolism coupled with a positive feedback loop between improving body condition and reduced flipper stroking frequency. In contrast, three additional seals carrying large, non-streamlined instrumentation saw a four-fold increase in energy partitioned toward locomotion, resulting in elevated FMRs and only half the mass gain of normally-swimming study animals. CONCLUSIONS: These results highlight the importance of keeping locomotion costs low for successful foraging in this species. In preparation for lactation and two fasting periods with high demands on energy reserves, migrating elephant seals utilize an economical foraging strategy whereby energy savings from reduced locomotion costs are shuttled towards somatic growth and fetal gestation. Remarkably, the energy requirements of this species, particularly during pregnancy, are 70-80 % lower than expected for mammalian carnivores, approaching or even falling below values predicted to be necessary to support basal metabolism in mammals of this size. PMID- 26380092 TI - Long-term trends of Nitrogen oxides and surface ozone concentrations in Tehran city, 2002-2011. AB - BACKGROUND AND AIM: Tropospheric ozone is a problem with multi aspects - hazard to human health, plant, and welfare and a key factor to climate change, air pollution and atmosphere chemistry, as well. Behavior of ozone and nitrogen oxides (NO, and NO2) concentration is highly complex and variable; therefore, their trends as short and long-term were significantly attended. Most of the studies were carried out on the behavior of pollutant concentrations in North America, Europe, and East Asia, but few studies have been conducted in west Asia. The aim of this study was to assess daily changes and long-term trend of ozone and nitrogen oxides concentrations in Tehran city, Iran from March 2002 to September 2011. MATERIAL AND METHODS: Data were collected from 18 air quality monitoring stations. The data were sorted as daily mean of 10 years (daily changes) and annual mean for each year (long-term trend). One-sample test was used to assess the statistical significance. RESULTS: Current findings indicated that changes of ozone, NO, and NO2 concentrations are dependent from job shifts and photochemical reactions. Annual mean concentrations of ozone and NO2 were gradually increased, long-term trend of ozone and NO2 concentration indicated. The correlation between long term trend of ozone and NO2 was significant (p < 0.05). CONCLUSION: The controlling program was the most important factor in long term concentration of ozone, and nitrogen oxides, but some problems and difficulties were accounted to perform controlling program. PMID- 26380093 TI - Precise navigation surgery of tumours in the lung in mouse models enabled by in situ fluorescence labelling with a killer-reporter adenovirus. AB - BACKGROUND: Current methods of image-guided surgery of tumours of the lung mostly rely on CT. A sensitive procedure of selective tumour fluorescence labelling would allow simple and high-resolution visualisation of the tumour for precise surgical navigation. METHODS: Human lung cancer cell lines H460 and A549 were genetically transformed to express red fluorescent protein (RFP). Tumours were grown subcutaneously for each cell line and harvested and minced for surgical orthotopic implantation on the left lung of nude mice. Tumour growth was measured by fluorescence imaging. After the tumours reached 5 mm in diameter, they were injected under fluorescence guidance with the telomerase-dependent green fluorescent protein (GFP)-containing adenovirus, OBP-401. Viral labelling of the lung tumours with GFP precisely colocalised with tumour RFP expression. Three days after administration of OBP-401, fluorescence-guided surgery (FGS) was performed. RESULTS: FGS of tumours in the lung was enabled by labelling with a telomerase-dependent adenovirus containing the GFP gene. Tumours in the lung were selectively and brightly labelled. FGS enabled complete lung tumour resection with no residual fluorescent tumour. CONCLUSIONS: FGS of tumours in the lung is feasible and more effective than bright-light surgery. PMID- 26380094 TI - Culture-centered approaches: the relevance of assessing emotional health for Latinos with type 2 diabetes. AB - OBJECTIVE: Within Latino culture, there is a belief that strong emotions can cause diabetes. Because of this belief and evidence regarding the bi-directional relationship between depression and diabetes, the objectives of this study were to determine if medical doctors are asking Latinos with diabetes about emotional problems and to assess attitudes toward professional help for emotional problems. RESEARCH DESIGN AND METHODS: Data come from the nationally representative National Latino and Asian American Study and the National Comorbidity Survey Replication study. Only Latino subsamples were included (n=3076). A smaller subsample with complete data (n=2568) was used for the inquiry outcome variable. Weighted chi(2) analysis and logistic regression were conducted to determine the likelihood of being asked about emotional problems and attitudes toward professional help. RESULTS: Latinos with mood disorders or anxiety (MD/AX; OR 2.84, 95% CI 2.02 to 4.00), diabetes only (OR 1.69, 95% CI 1.06 to 2.69), and co occurring diabetes and MD/AX (OR 6.67, 95% CI 2.33 to 19.04) were more likely to be asked about emotional problems, relative to Latinos without diabetes or MD/AX. A minority of respondents with diabetes (32%) were asked about emotional problems. Respondents with diabetes only were more likely to feel comfortable talking to a professional for personal problems compared with those without diabetes or MD/AX (OR 1.44, 95% CI 0.99 to 2.09). Although the relationship between having diabetes and feeling comfortable taking to a professional is not statistically significant, z-test statistics indicate that having diabetes influences attitudes about discussing emotional problems. CONCLUSIONS: Among Latinos, having diabetes is associated with greater likelihood of being asked about emotional problems and feeling comfortable talking to a professional about personal problems. Consistent with the cultural relevance of emotions as a cause of diabetes, asking about emotional problems may be a useful approach for engaging Latinos into a discussion about their diabetes self-care activities. PMID- 26380095 TI - Inpatient HbA1c testing: a prospective observational study. AB - OBJECTIVE: To use admission inpatient glycated hemoglobin (HbA1c) testing to help investigate the prevalence of unrecognized diabetes, the cumulative prevalence of unrecognized and known diabetes, and the prevalence of poor glycemic control in both. Moreover, we aimed to determine the 6-month outcomes for these patients. Finally, we aimed to assess the independent association of diabetes with these outcomes. RESEARCH DESIGN AND METHODS: Prospective observational cohort study conducted in a tertiary hospital in Melbourne, Australia. PATIENTS: A cohort of 5082 inpatients >=54 years admitted between July 2013 and January 2014 underwent HbA1c measurement. A previous diagnosis of diabetes was obtained from the hospital medical record. Patient follow-up was extended to 6 months. RESULTS: The prevalence of diabetes (known and unrecognized) was 34%. In particular, we identified that unrecognized but HbA1c-confirmed diabetes in 271 (5%, 95% CI 4.7% to 6.0%) patients, previously known diabetes in 1452 (29%, 95% CI 27.3% to 29.8%) patients; no diabetes in 3359 (66%, 95% CI 64.8-67.4%) patients. Overall 17% (95% CI 15.3% to 18.9%) of patients with an HbA1c of >6.5% had an HbA1c >=8.5%. After adjusting for age, gender, Charlson Index score, estimated glomerular filtration rate, and hemoglobin levels, with admission unit treated as a random effect, patients with previously known diabetes had lower 6-month mortality (OR 0.69, 95% CI 0.56 to 0.87, p=0.001). However, there were no significant differences in proportions of intensive care unit admission, mechanical ventilation or readmission within 6 months between the 3 groups. CONCLUSIONS: Approximately one third of all inpatients >=54 years of age admitted to hospital have diabetes of which about 1 in 6 was previously unrecognized. Moreover, poor glycemic control was common. Proportions of intensive care unit admission, mechanical ventilation, or readmission were similar between the groups. Finally, diabetes was independently associated with lower 6-month mortality. PMID- 26380096 TI - Obesity and inflammation markers in relation to leukocyte telomere length in a cross-sectional study of persons with Barrett's esophagus. AB - BACKGROUND: Telomere shortening is associated with increasing age, male gender and lifestyle factors such as obesity and smoking. Inflammation has also been implicated in cellular senescence and may promote telomere shortening in chronic conditions such as obesity and diabetes. However, little is known about the relationship between markers of obesity and inflammation, and leukocyte telomere length (LTL). METHODS: LTL was measured using quantitative polymerase chain reaction in peripheral leukocytes from 295 individuals diagnosed with Barrett's esophagus (BE) between 1995 and 2009. Data on lifestyle variables including obesity and smoking were collected at in-person interviews. Biomarkers of obesity (leptin, adiponectin), diabetes (glucose, insulin), inflammation (C-reactive protein, Interleukin-6, surface tumor necrosis factor receptor (sTNFR) I & II) and oxidative stress (F2-isoprostanes) were measured in stored blood samples. We examined associations between these covariates and LTL in a cross-sectional analysis using linear and logistic regression models, adjusting for possible confounders. RESULTS: LTL was significantly associated with age (r = -0.30, p < 0.001), gender (r = 0.14 for females, p = 0.01) and inversely associated with cigarette pack-years (r = -0.11, p = 0.04). Odds of having short LTL were significantly higher for participants in the highest tertile for sTNF-RI (Odds ratio adjusted for age, gender, smoking, and obesity = 2.19; 95 % CI 1.00-4.85, p trend = 0.02). LTL was not significantly associated with any other lifestyle factors, including smoking or obesity, or other inflammation-, obesity-/diabetes related biomarkers measured. CONCLUSIONS: Increasing age, male gender, smoking history, and sTNF-RI levels were associated with short LTL among persons with BE but no correlations were observed between LTL and other inflammatory markers or measures of obesity. Larger longitudinal studies are necessary in order to further establish the potential relationships between obesity, inflammation markers and LTL. PMID- 26380097 TI - Cardioprotective role of zofenopril in patients with acute myocardial infarction: a pooled individual data analysis of four randomised, double-blind, controlled, prospective studies. AB - BACKGROUND: Early administration of zofenopril following acute myocardial infarction (AMI) proved to be prognostically beneficial in the four individual randomised, double-blind, parallel-group, prospective SMILE (Survival of Myocardial Infarction Long-term Evaluation) studies. In the present analysis, we evaluated the cumulative efficacy of zofenopril by pooling individual data from the four SMILE studies. METHODS: 3630 patients with AMI were enrolled and treated for 6-48 weeks with zofenopril 30-60 mg/day (n=1808), placebo (n=951), lisinopril 5-10 mg/day (n=520) or ramipril 10 mg/day (n=351). The primary study end point of this pooled analysis was set to 1 year combined occurrence of death or hospitalisation for cardiovascular (CV) causes. RESULTS: Occurrence of major CV outcomes was significantly reduced with zofenopril versus placebo (-40%; HR=0.60, 95% CI 0.49 to 0.74; p=0.0001) and versus the other ACE inhibitors (-23%; HR=0.77, 0.63 to 0.95; p=0.015). The risk reduction observed under treatment with the other ACE inhibitors was nearly statistically significant (-22%; HR=0.78, 0.60 to 1.02; p=0.072). The benefit of zofenopril versus placebo was already evident after the first 6 weeks of treatment (-28%; HR=0.72, 0.54 to 0.97; p=0.029), while this was not the case for the other ACE inhibitors (-19%; HR=0.81, 0.57 to 1.17; p=0.262). In this early phase of treatment, zofenopril showed a non-significant trend towards a larger reduction in CV events versus the other ACE inhibitors (-11%; HR=0.89, 0.69 to 1.15; p=0.372). CONCLUSIONS: The pooled data analysis from the SMILE Programme confirms the favourable effects of zofenopril treatment in patients with post-AMI and its long-term benefit in terms of prevention of CV morbidity and mortality. PMID- 26380098 TI - Atrioesophageal fistula following ablation procedures for atrial fibrillation: systematic review of case reports. AB - BACKGROUND: Atrioesophageal fistula (AEF) is a rare but serious adverse event of atrial fibrillation (AF) ablation. OBJECTIVE: To identify the clinical characteristics of AEF following ablation procedures for AF and determine the associated mortality. METHODS: A systematic review of observational cases of AEF following ablation procedures for AF was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement protocol. RESULTS: 53 cases were identified. Mean age was 54+/-13 years; 73% (39/53) of cases occurred in males. Mean interval between procedure and presentation was 20+/-12 days, ranging from 2 to 60 days. AEF was observed in 12 patients who underwent surgical radiofrequency ablation (RFA) and in 41 patients with percutaneous RFA. Fever was the most common presenting symptom (n=44) followed by neurological deficits (n=27) and haematemesis (n=19). CT of the chest (n=27) was the preferred diagnostic test. Patients who did not receive a primary esophageal repair were more likely to have a deadly outcome (34% vs 83%; p<0.05). No difference in mortality rate was found between patients who underwent surgical RFA when compared with percutaneous RFA (58% vs 56%; p=0.579). No association was found between onset of symptoms and mortality (19+/-10 vs 23+/-14 days; p=0.355). CONCLUSIONS: AEF following ablation procedures for AF is a serious complication with high mortality rates. Presenting symptoms most often include a triad of fever, neurological deficit and/or haematemesis within 60 days of procedure. The preferred diagnostic test is CT of the chest. The treatments of choice is surgical repair. PMID- 26380099 TI - Impact of frailty on outcomes after percutaneous coronary intervention: a prospective cohort study. AB - BACKGROUND: Average life expectancy is rising, resulting in increasing numbers of elderly, frail individuals presenting with coronary artery disease and requiring percutaneous coronary intervention (PCI). PCI can be of value for this population, but little is known about the balance of benefit versus risk, particularly in the frail. OBJECTIVE: To determine the relationship between frailty and clinical outcomes in patients undergoing PCI. METHODS: Patients undergoing PCI, for either stable angina or acute coronary syndrome, were prospectively assessed for frailty using the Canadian Study of Health and Ageing Clinical Frailty Scale. Demographics, clinical and angiographic data were extracted from the hospital database. Mortality was obtained from the Office of National Statistics. RESULTS: Frailty was assessed in 745 patients undergoing PCI. The mean age of patients was 62+/-12 years and 70% were males. The median frailty score was 3 (IQR 2-4). A frailty score >=5, indicating significant frailty, was present in 81 (11%) patients. Frail patients required longer hospitalisation after PCI. Frailty was also associated with increased 30-day (HR 4.8, 95% CI 1.4 to 16.3, p=0.013) and 1 year mortality (HR 5.9, 95% CI 2.5 to 13.8, p<0.001). Frailty was a predictor of length of hospital stay and mortality, independent of age, gender and comorbidities. CONCLUSIONS: A simple assessment of frailty can help predict mortality and the length of hospital stay, and may therefore guide healthcare providers to plan PCI and appropriate resources for frail patients. PMID- 26380100 TI - Effect of catheter ablation on quality of life in patients with atrial fibrillation and its correlation with arrhythmia outcome. AB - OBJECTIVE: To assess the effect of catheter ablation on atrial fibrillation (AF) symptoms and quality of life (QoL). METHODS: Patients with AF scheduled for ablation were recruited. Pulmonary vein isolation (PVI) was performed and complex fractionated atrial electrogram (CFAE)+/-linear ablation undertaken in patients in AF despite PVI. QoL and AF symptoms were assessed using SF-36 V2 and Atrial Fibrillation Effect on Quality-of-Life (AFEQT) questionnaires before and 3 months after ablation. Change in QoL scores after ablation was correlated with clinical parameters and the extent of ablation. Magnitude of QoL change was compared between AFEQT and SF-36 physical component summary (PCS) and mental component summary (MCS) scores and correlated with arrhythmia outcome. RESULTS: 80 patients were studied. Summative and individual health scores for both AFEQT (51.5+/-22.0 vs 81.3+/-18.2; p<0.01) and SF-36 (PCS 43.3+/-10.5 vs 47.9+/-11.3; p<0.01 and MCS 45.0+/-11.5 vs 51.5+/-9.4; p<0.01) improved significantly in patients who maintained sinus rhythm after ablation, but not in those with recurrent AF. Improvement in AFEQT (25.4+/-19) was significantly greater than change in PCS (6.8+/-6.4; p<0.01) and MCS (8.5+/-7.9; p<0.01) scores and correlated more closely with arrhythmia outcome (AFEQT r=0.55; PCS r=0.26; MCS r=0.30). CONCLUSIONS: Patients who maintained sinus rhythm after ablation had a significant improvement in AF symptoms and QoL; however, no improvement was observed in patients with recurrent AF. QoL change after ablation did not correlate with baseline clinical parameters or ablation strategy. AF specific QoL scales are more responsive to change and correlate better with ablation outcome. PMID- 26380102 TI - An unusual presentation of patent foramen ovale. AB - We report a case of retinal artery occlusion in a young adult in early pregnancy found to have a patent foramen ovale as the source of the embolism. This report suggests the importance of early cardiac investigation in such individuals. PMID- 26380101 TI - Significantly reduced lymphadenopathy, salivary gland infiltrates and proteinuria in MRL-lpr/lpr mice treated with ultrasoluble curcumin/turmeric: increased survival with curcumin treatment. AB - OBJECTIVES: Commercial curcumin (CU), derived from food spice turmeric (TU), has been widely studied as a potential therapeutic for a variety of oncological and inflammatory conditions. Lack of solubility/bioavailability has hindered curcumin's therapeutic efficacy in human diseases. We have solubilised curcumin in water applying heat/pressure, obtaining up to 35-fold increase in solubility (ultrasoluble curcumin (UsC)). We hypothesised that UsC or ultrasoluble turmeric (UsT) will ameliorate systemic lupus erythematosus (SLE) and Sjogren's syndrome (SS)-like disease in MRL-lpr/lpr mice. METHODS: Eighteen female MRL-lpr/lpr (6 weeks old) and 18 female MRL-MpJ mice (6 weeks old) were used. Female MRL-lpr/lpr mice develop lupus-like disease at the 10th week and die at an average age of 17 weeks. MRL-MpJ mice develop lupus-like disease around 47 weeks and typically die at 73 weeks. Six mice of each strain received autoclaved water only (lpr-water or MpJ-water group), UsC (lpr-CU or MpJ-CU group) or UsT (lpr-TU or MpJ-TU group) in the water bottle. RESULTS: UsC or UsT ameliorates SLE in the MRL-lpr/lpr mice by significantly reducing lymphoproliferation, proteinuria, lesions (tail) and autoantibodies. lpr-CU group had a 20% survival advantage over lpr-water group. However, lpr-TU group lived an average of 16 days shorter than lpr-water group due to complications unrelated to lupus-like illness. CU/TU treatment inhibited lymphadenopathy significantly compared with lpr-water group (p=0.03 and p=0.02, respectively) by induction of apoptosis. Average lymph node weights were 2606+/ 1147, 742+/-331 and 385+/-68 mg, respectively, for lpr-water, lpr-CU and lpr-TU mice. Transferase dUTP nick end labelling assay showed that lymphocytes in lymph nodes of lpr-CU and lpr-TU mice underwent apoptosis. Significantly reduced cellular infiltration of the salivary glands in the lpr-TU group compared with the lpr-water group, and a trend towards reduced kidney damage was observed in the lpr-CU and lpr-TU groups. CONCLUSIONS: These studies show that UsC/UsT could prove useful as a therapeutic intervention in SLE/SS. PMID- 26380103 TI - Making clinical academic careers more attractive: views from questionnaire surveys of senior UK doctors. AB - OBJECTIVES: To report on doctors' reasons, as expressed to our research group, for choosing academic careers and on factors that would make a career in clinical academic medicine more attractive to them. DESIGN: Postal, email and web questionnaires. SETTING: UK. PARTICIPANTS: A total of 6936 UK-trained doctors who graduated in 1996, 1999 and 2000. MAIN OUTCOME MEASURES: Open-ended comments about a career in clinical academic medicine. RESULTS: Of doctors who provided reasons for pursuing a long-term career in clinical academic medicine, the main reasons were enjoyment of academic work and personal satisfaction, whether expressed directly in those terms, or in terms of intellectual stimulation, enjoyment of research, teaching and the advancement of medicine, and the job being more varied than and preferable to clinical work alone. Doctors' suggestions for making clinical academic medicine more attractive included improved pay and job security, better funding of research, greater availability of academic posts, more dedicated time for research (and less service work) and more support and mentoring. Women were more likely than men to prioritise flexible working hours and part-time posts. CONCLUSIONS: Medical schools could provide more information, as part of student teaching, about the opportunities for and realities of a career in clinical academic medicine. Women, in particular, commented that they lacked the role models and information which would encourage them to consider seriously an academic career. Employers could increase academic opportunities by allowing more time for teaching, research and study and should assess whether job plans make adequate allowance for academic work. PMID- 26380104 TI - Recurrence of crystalline nephropathy after kidney transplantation in APRT deficiency and primary hyperoxaluria. AB - PURPOSE OF REVIEW: To provide transplant physicians with a summary of the pathogenesis and diagnosis of adenine phosphoribosyl transferase (APRT) deficiency and primary hyperoxaluria and, focussed on kidney transplantation, and to discuss interventions aimed at preventing and treating the recurrence of crystalline nephropathy in renal transplant recipients. SOURCE OF INFORMATION: Pubmed literature search. SETTING: Primary hyperoxaluria and APRT deficiency are rare inborn errors of human metabolism. The hallmark of these diseases is the overproduction and urinary excretion of compounds (2,8 dihydroxyadenine in APRT deficiency, oxalate in primary hyperoxaluria) that form urinary crystals. Although recurrent urolithiasis represents the main clinical feature of these diseases, kidney injury can occur as a result of crystal precipitation within the tubules and interstitium, a condition referred to as crystalline nephropathy. Some patients develop end-stage renal disease (ESRD) and may become candidates for kidney transplantation. Since kidney transplantation does not correct the underlying metabolic defect, transplant recipients have a high risk of recurrence of crystalline nephropathy, which can lead to graft loss. In some instances, the disease remains undiagnosed until after the occurrence of ESRD or even after kidney transplantation. KEY MESSAGES: Patients with APRT deficiency or primary hyperoxaluria may develop ESRD as a result of crystalline nephropathy. In the absence of diagnosis and adequate management, the disease is likely to recur after kidney transplantation, which often leads to rapid loss of renal allograft function. Primary hyperoxaluria, but not APRT deficiency, becomes a systemic disease at low GFR with oxalate deposition leading to malfunction in non-renal organs (systemic oxalosis). We suggest that these diagnoses should be considered in patients with low glomerular filtration rate (GFR) and a history of kidney stones. In APRT deficiency, stones may be confused with uric acid stones, unless specialized techniques are used (infrared spectroscopy or X-ray crystallography for urinary crystals or stone analysis; Fourier transform infrared microscopy for crystals in kidney biopsy). Where these are unavailable, and for confirmation, the diagnosis can be made by measurement of enzyme activity in red blood cell lysates or by genetic testing. In patients with primary hyperoxaluria, levels of urinary and plasma oxalate; and the presence of nearly pure calcium oxalate monohydrate in stones, which often also have an unusually pale colour and unorganized structure, increase diagnostic suspicion. Molecular genetic testing is the criterion measure. Lifelong allopurinol therapy, with high fluid intake if appropriate, may stabilize kidney function in APRT deficiency; if ESRD has occurred or is near, results with kidney transplantation after initiation of allopurinol are excellent. In primary hyperoxaluria recognized before ESRD, pyridoxine treatment and high fluid intake may lead to a substantial decrease in urinary calcium oxalate supersaturation and prevent renal failure. In non responsive patients or those recognized later in their disease, liver transplantation cures the underlying defect and should be considered when the GFR falls below 30 ml/min/1.73 m(2); in those which or near ESRD, liver transplantation and intensive dialysis before kidney transplantation may be considered to reduce the total body oxalate burden before kidney transplantation. LIMITATIONS: The availability of diagnostic tests varies between countries and centres. Data on long term outcomes after kidney transplantation are limited, especially for APRT deficiency patients. IMPLICATIONS: Increasing transplant physicians knowledge of APRT deficiency and primary hyperoxaluria should enable them to implement adequate diagnostic and therapeutic interventions, thereby achieving good outcomes after kidney transplantation. PMID- 26380105 TI - Expression and Purification of the Recombinant Cytochrome P450 CYP141 Protein of Mycobacterium Tuberculosis as a Diagnostic Tool and Vaccine Production. AB - BACKGROUND: Tuberculosis (TB) is regarded as a health problem worldwide, particularly in developing countries. Mycobacterium tuberculosis (M. tuberculosis) is the cause of this disease. Approximately two billion people worldwide are infected by M. tuberculosis and annually about two million individuals die in consequence. Forty million people are estimated to die because of M. tuberculosis over the next 25 years if the measures for controlling this infection are not extensively developed. In the vaccination field, Bacillus Calmette-Guerin (BCG) is still the most effective vaccine but it shows no efficacy in adult pulmonary patients. One of the other problems regarding TB is its appropriate diagnosis. OBJECTIVES: In this experimental study, the recombinant cytochrome P450 CYP141 protein of M. tuberculosis was expressed and purified to be used as a vaccine candidate and diagnostic purpose in subsequent investigations. MATERIALS AND METHODS: The optimization of the cytochrome P450 CYP141 protein expression was evaluated in different conditions. Then, this protein was purified with a resin column of nickel-nitrilotriacetic acid and investigated via Sodium Dodecyl Sulfate Polyacrylamide Gel Electrophoresis (SDS PAGE) and Western Blotting. RESULTS: The highest expression of the cytochrome P450 CYP141 protein was obtained by the addition of 1 mM of isopropyl beta-D-1 thiogalactopyranoside (IPTG) to the bacterial culture grown to an optical density at 600 nm (OD600) of 0.6, 16 hours after induction. This protein was subsequently purified with a purification of higher than 80%. The results of Western Blotting indicated that the purified protein was specifically detected. CONCLUSIONS: In this experimental study, for the first time in Iran the expression and purification of this recombinant protein was done successfully. This recombinant protein could be used as a vaccine candidate and diagnostic purpose in subsequent investigations. PMID- 26380106 TI - Effect of Motivational Interviewing on a Weight Loss Program Based on the Protection Motivation Theory. AB - BACKGROUND: The prevalence of overweight and obesity is on the increase the world over, which imposes an ever-increasing burden on societies and health care systems. OBJECTIVES: This study sought to investigate the effect of motivational interviewing (MI) on a weight-loss program based on the protection motivation theory (PMT). PATIENTS AND METHODS: This randomized clinical trial study, comprising pretest-posttest with a control group, was conducted on 150 overweight and obese women attending a private nutrition clinic for the first time. Samples were randomly selected using the clinic's records and then allocated to three groups (50 women in each group) receiving: 1) a standard weight-control program; 2) motivational interviewing; and 3) MI plus intention intervention. Data were collected using a researcher-made questionnaire through in-person interviews and were analyzed using SPSS (version 11) and statistical tests, including the Kruskal-Wallis test, one-way analysis of variance, paired t-test, and linear regression model. RESULTS: In the two intervention groups, the PMT construct scores, namely susceptibility (P = 0.001), severity (P = 0.001), rewards (P =0.004), self-efficacy (P = 0.001), response efficacy (P = 0.001), and costs (P = 0.014), were significantly increased compared to those in the control group. The anthropometric status was statistically significant in the MI group (P = 0.001) and the MI plus intention-intervention group (P = 0.001) at 2 months' follow-up, while in the control group, weight was meaningfully different after the intervention (P = 0.027). Weight was different between the groups after the intervention, with the Tukey test demonstrating that the differences were statistically significant between the control group and the MI group. CONCLUSIONS: Our results demonstrated that MI, combined with the implementation of intention intervention, increased weight loss and PMT construct scores in our study population. PMID- 26380107 TI - Constipation Risk in Patients Undergoing Abdominal Surgery. AB - BACKGROUND: Problems regarding bowel elimination are quite common in patients undergoing abdominal surgery. OBJECTIVES: To determine constipation risk before the surgery, bowel elimination during postoperative period, and the factors affecting bowel elimination. PATIENTS AND METHODS: This is a cross-sectional study. It was conducted in a general surgery ward of a university hospital in Zonguldak, Turkey between January 2013 and May 2013. A total of 107 patients were included in the study, who were selected by convenience sampling. Constipation Risk Assessment Scale (CRAS), patient information form, medical and nursing records were used in the study. RESULTS: The mean age of the patients was found to be 55.97 +/- 15.74 (year). Most of the patients have undergone colon (37.4%) and stomach surgeries (21.5%). Open surgical intervention (83.2%) was performed on almost all patients (96.3%) under general anesthesia. Patients were at moderate risk for constipation with average scores of 11.71 before the surgery. A total of 77 patients (72%) did not have bowel elimination problem during postoperative period. The type of the surgery (P < 0.05), starting time for oral feeding after the surgery (P < 0.05), and mobilization (P < 0.05) were effective on postoperative bowel elimination. CONCLUSIONS: There is a risk for constipation after abdominal surgery. Postoperative practices are effective on the risk of constipation. PMID- 26380108 TI - Indicators for Evaluating the Performance and Quality of Care of Ambulatory Care Nurses. AB - The quality and safety of nursing care vary from one service to another. We have only very limited information on the quality and safety of nursing care in outpatient settings, an expanding area of practice. Our aim in this study was to make available, from the scientific literature, indicators potentially sensitive to nursing that can be used to evaluate the performance of nursing care in outpatient settings and to integrate those indicators into the theoretical framework of Dubois et al. (2013). We conducted a scoping review in three databases (CINAHL, MEDLINE, and EMBASE) and the bibliographies of selected articles. From a total of 116 articles, we selected 22. The results of our study not only enable that framework to be extended to ambulatory nursing care but also enhance it with the addition of five new indicators. Our work offers nurses and managers in ambulatory nursing units indicators potentially sensitive to nursing that can be used to evaluate performance. For researchers, it presents the current state of knowledge on this construct and a framework with theoretical foundations for future research in ambulatory settings. This work opens an unexplored field for further research. PMID- 26380109 TI - Nummular Eczema of Breast: A Potential Dermatologic Complication after Mastectomy and Subsequent Breast Reconstruction. AB - Purposes. The present paper reports clinical cases where nummular eczema developed during the course of breast reconstruction by means of implantation and evaluates the occurrence patterns and ratios of this complication. Methods. 1662 patients undergoing breast reconstruction were reviewed. Patients who developed nummular eczema during the treatment were selected, and a survey was conducted on these patients regarding three items: (1) the stage of the treatment at which nummular eczema developed; (2) time required for the lesion to heal; (3) location of the lesion on the reconstructed breast(s). Furthermore, histopathological examination was conducted to elucidate the etiology of the lesion. Results. 48 patients (2.89%) developed nummular eczema. The timing of onset varied among these patients, with lesions developing after the placement of tissue expanders for 22 patients (45.8%); after the tissue expanders were replaced with silicone implants for 12 patients (25%); and after nipple-areola complex reconstruction for 14 patients (29.2%). Nummular eczema developed both in periwound regions (20 cases: 41.7%) and in nonperiwound regions (32 cases: 66.7%). Histopathological examination showed epidermal acanthosis, psoriasiform patterns, and reduction of sebaceous glands. Conclusions. Surgeons should recognize that nummular eczema is a potential complication of breast reconstruction with tissue expanders and silicone implants. PMID- 26380111 TI - Forceps, Actual Use, and Potential Cesarean Section Prevention: Study in a Selected Mexican Population. AB - OBJECTIVE: Assessment of the frequency of complications observed with various forceps and operative vaginal delivery (OVD) techniques performed at the ABC Medical Center (Mexico City) to evaluate their safety, bearing in mind the importance of decreasing our country's high cesarean section incidence. METHODS: We reviewed 5,375 deliveries performed between the years 2007 and 2012, only 146 were delivered by OVD. RESULTS: Only 1.0% of the cases had a serious, life threatening situation (uterine rupture). The Simpson forceps was the most favored instrument (46%) due to its simplicity of use, effectiveness, and familiarity. Prophylactic use was the most common indication (30.8%) and significant complications observed were vaginal lacerations (p = 0.016), relative risk (RR) of 3.4 (95% confidence interval [CI]: 1.15-10.04), and fourth degree perineal tear (p = 0.016), RR of 3.4 (95% CI: 1.15-10.04). CONCLUSIONS: Forceps use and other OVD techniques are a safe alternative to be considered, diminishing C section incidence and its complications. PMID- 26380110 TI - Using the Promise of Sonodynamic Therapy in the Clinical Setting against Disseminated Cancers. AB - Sonodynamic therapy (SDT) is a form of ultrasound therapy in which specialized chemotherapeutic agents known as sonosensitizers are administered to increase the efficacy of ultrasound-mediated preferential damage of neoplastic cells. Multiple in vitro and in vivo studies have indicated that SDT has the ability to exhibit profound physical and chemical changes on cellular structure. As supportive as the data have been, assessment of this method at the clinical level has been limited to only solid tumors. Although SDT has shown efficacy against multiple adherent neoplastic cell lines, it has also shown particular promise with leukemia-derived cell lines. Potential procedures to administer SDT to leukemia patients are heating the appendages as ultrasound is applied to these areas (Heat and Treat), using an ultrasound probe to scan the body for malignant growths (Target and Destroy), and extracorporeal blood sonication (EBS) through dialysis. Each method offers a unique set of benefits and concerns that will need to be evaluated in preclinical mammalian models of malignancy before clinical examination can be considered. PMID- 26380112 TI - Inner Synovial Membrane Footprint of the Anterior Elbow Capsule: An Arthroscopic Boundary. AB - Introduction. The purpose of this study is to describe the inner synovial membrane (SM) of the anterior elbow capsule, both qualitatively and quantitatively. Materials and Methods. Twenty-two cadaveric human elbows were dissected and the distal humerus and SM attachments were digitized using a digitizer. The transepicondylar line (TEL) was used as the primary descriptor of various landmarks. The distance between the medial epicondyle and medial SM edge, SM apex overlying the coronoid fossa, the central SM nadir, and the apex of the SM insertion overlying the radial fossa and distance from the lateral epicondyle to lateral SM edge along the TEL were measured and further analyzed. Gender and side-to-side statistical comparisons were calculated. Results. The mean age of the subjects was 80.4 years, with six male and five female cadavers. The SM had a distinctive double arched attachment overlying the radial and coronoid fossae. No gender-based or side-to-side quantitative differences were noted. In 18 out of 22 specimens (81.8%), an infolding extension of the SM was observed overlying the medial aspect of the trochlea. The SM did not coincide with the outer fibrous attachment in any specimen. Conclusion. The humeral footprint of the synovial membrane of the anterior elbow capsule is more complex and not as capacious as commonly understood from the current literature. The synovial membrane nadir between the two anterior fossae may help to explain and hence preempt technical difficulties, a reduction in working arthroscopic volume in inflammatory and posttraumatic pathologies. This knowledge should allow the surgeon to approach this aspect of the anterior elbow compartment space with the confidence that detachment of this synovial attachment, to create working space, does not equate to breaching the capsule. Alternatively, stripping the synovial attachment from the anterior humerus does not constitute an anterior capsular release. PMID- 26380113 TI - Association Study between Idiopathic Scoliosis and Polymorphic Variants of VDR, IGF-1, and AMPD1 Genes. AB - Idiopathic scoliosis (IS) is a complex genetic disorder of the musculoskeletal system, characterized by three-dimensional rotation of the spine with unknown etiology. For the aims of the current study we selected 3 single nucleotide polymorphisms with a low incidence of the polymorphic allele in Bulgarian population, AMPD1 (rs17602729), VDR (rs2228670), and IGF-1 (rs5742612), trying to investigate the association between these genetic polymorphisms and susceptibility to and progression of IS. The polymorphic regions of the genes were amplified by polymerase chain reaction (PCR). The PCR products were cleaved with the appropriate restriction enzymes. The statistical analysis was performed by Pearson's chi-squared test. A value of p < 0.05 was considered to be statistically significant. In conclusion, this case-control study revealed no statistically significant association between the VDR, IGF-1, and AMPD1 polymorphisms and the susceptibility to IS or curve severity in Bulgarian patients. Replication case-control studies will be needed to examine the association between these candidate-genes and IS in different populations. The identification of molecular markers for IS could be useful for early detection and prognosis of the risk for a rapid progression of the curve. That would permit early stage treatment of the patient with the least invasive procedures. PMID- 26380114 TI - New Insights on Retrieval-Induced and Ongoing Memory Consolidation: Lessons from Arc. AB - The mainstream view on the neurobiological mechanisms underlying memory formation states that memory traces reside on the network of cells activated during initial acquisition that becomes active again upon retrieval (reactivation). These activation and reactivation processes have been called "conjunctive trace." This process implies that singular molecular events must occur during acquisition, strengthening the connection between the implicated cells whose synchronous activity must underlie subsequent reactivations. The strongest experimental support for the conjunctive trace model comes from the study of immediate early genes such as c-fos, zif268, and activity-regulated cytoskeletal-associated protein. The expressions of these genes are reliably induced by behaviorally relevant neuronal activity and their products often play a central role in long term memory formation. In this review, we propose that the peculiar characteristics of Arc protein, such as its optimal expression after ongoing experience or familiar behavior, together with its versatile and central functions in synaptic plasticity could explain how familiarization and recognition memories are stored and preserved in the mammalian brain. PMID- 26380115 TI - Retrosplenial Cortex and Long-Term Memory: Molecules to Behavior. AB - The retrosplenial cortex (RSC) is reciprocally connected with the hippocampus and various parahippocampal cortical regions, suggesting that RSC is well-positioned to contribute to hippocampal-dependent memory. Consistent with this, substantial behavioral evidence indicates that RSC is essential for consolidating and/or retrieving contextual and spatial memories. In addition, there is growing evidence that RSC neurons undergo activity-dependent plastic changes during memory formation and retrieval. In this paper we review both the behavioral and cellular/molecular data and posit that the RSC has a particularly important role in the storage and retrieval of spatial and contextual memories perhaps due its involvement in binding together multiple cues in the environment. We identify remaining questions and avenues for future research that take advantage of emerging methods to selectively manipulate RSC neurons both spatially and temporally and to image the RSC in awake, behaving animals. PMID- 26380116 TI - Evidence of Maintenance Tagging in the Hippocampus for the Persistence of Long Lasting Memory Storage. AB - The synaptic tagging and capture (STC) hypothesis provides a compelling explanation for synaptic specificity and facilitation of long-term potentiation. Its implication on long-term memory (LTM) formation led to postulate the behavioral tagging mechanism. Here we show that a maintenance tagging process may operate in the hippocampus late after acquisition for the persistence of long lasting memory storage. The proposed maintenance tagging has several characteristics: (1) the tag is transient and time-dependent; (2) it sets in a late critical time window after an aversive training which induces a short lasting LTM; (3) exposing rats to a novel environment specifically within this tag time window enables the consolidation to a long-lasting LTM; (4) a familiar environment exploration was not effective; (5) the effect of novelty on the promotion of memory persistence requires dopamine D1/D5 receptors and Arc expression in the dorsal hippocampus. The present results can be explained by a broader version of the behavioral tagging hypothesis and highlight the idea that the durability of a memory trace depends either on late tag mechanisms induced by a training session or on events experienced close in time to this tag. PMID- 26380118 TI - Muscarinic ACh Receptors Contribute to Aversive Olfactory Learning in Drosophila. AB - The most studied form of associative learning in Drosophila consists in pairing an odorant, the conditioned stimulus (CS), with an unconditioned stimulus (US). The timely arrival of the CS and US information to a specific Drosophila brain association region, the mushroom bodies (MB), can induce new olfactory memories. Thus, the MB is considered a coincidence detector. It has been shown that olfactory information is conveyed to the MB through cholinergic inputs that activate acetylcholine (ACh) receptors, while the US is encoded by biogenic amine (BA) systems. In recent years, we have advanced our understanding on the specific neural BA pathways and receptors involved in olfactory learning and memory. However, little information exists on the contribution of cholinergic receptors to this process. Here we evaluate for the first time the proposition that, as in mammals, muscarinic ACh receptors (mAChRs) contribute to memory formation in Drosophila. Our results show that pharmacological and genetic blockade of mAChRs in MB disrupts olfactory aversive memory in larvae. This effect is not explained by an alteration in the ability of animals to respond to odorants or to execute motor programs. These results show that mAChRs in MB contribute to generating olfactory memories in Drosophila. PMID- 26380117 TI - Behavioral Tagging: A Translation of the Synaptic Tagging and Capture Hypothesis. AB - Similar molecular machinery is activated in neurons following an electrical stimulus that induces synaptic changes and after learning sessions that trigger memory formation. Then, to achieve perdurability of these processes protein synthesis is required for the reinforcement of the changes induced in the network. The synaptic tagging and capture theory provided a strong framework to explain synaptic specificity and persistence of electrophysiological induced plastic changes. Ten years later, the behavioral tagging hypothesis (BT) made use of the same argument, applying it to learning and memory models. The hypothesis postulates that the formation of lasting memories relies on at least two processes: the setting of a learning tag and the synthesis of plasticity related proteins, which once captured at tagged sites allow memory consolidation. BT explains how weak events, only capable of inducing transient forms of memories, can result in lasting memories when occurring close in time with other behaviorally relevant experiences that provide proteins. In this review, we detail the findings supporting the existence of BT process in rodents, leading to the consolidation, persistence, and interference of a memory. We focus on the molecular machinery taking place in these processes and describe the experimental data supporting the BT in humans. PMID- 26380119 TI - Molecular Mechanisms of Memory Consolidation, Reconsolidation, and Persistence. PMID- 26380120 TI - Involvement of Adult Hippocampal Neurogenesis in Learning and Forgetting. AB - Adult hippocampal neurogenesis is a process involving the continuous generation of newborn neurons in the hippocampus of adult animals. Mounting evidence has suggested that hippocampal neurogenesis contributes to some forms of hippocampus dependent learning and memory; however, the detailed mechanism concerning how this small number of newborn neurons could affect learning and memory remains unclear. In this review, we discuss the relationship between adult-born neurons and learning and memory, with a highlight on recently discovered potential roles of neurogenesis in pattern separation and forgetting. PMID- 26380121 TI - Autobiographical Memory Disturbances in Depression: A Novel Therapeutic Target? AB - Major depressive disorder (MDD) is characterized by a dysfunctional processing of autobiographical memories. We review the following core domains of deficit: systematic biases favoring materials of negative emotional valence; diminished access and response to positive memories; a recollection of overgeneral memories in detriment of specific autobiographical memories; and the role of ruminative processes and avoidance when dealing with autobiographical memories. Furthermore, we review evidence from functional neuroimaging studies of neural circuits activated by the recollection of autobiographical memories in both healthy and depressive individuals. Disruptions in autobiographical memories predispose and portend onset and maintenance of depression. Thus, we discuss emerging therapeutics that target memory difficulties in those with depression. We review strategies for this clinical domain, including memory specificity training, method-of-loci, memory rescripting, and real-time fMRI neurofeedback training of amygdala activity in depression. We propose that the manipulation of the reconsolidation of autobiographical memories in depression might represent a novel yet largely unexplored, domain-specific, therapeutic opportunity for depression treatment. PMID- 26380122 TI - Genotype-Dependent Difference in 5-HT2C Receptor-Induced Hypolocomotion: Comparison with 5-HT2A Receptor Functional Activity. AB - In the present study behavioral effects of the 5-HT2C serotonin receptor were investigated in different mouse strains. The 5-HT2C receptor agonist MK-212 applied intraperitoneally induced significant dose-dependent reduction of distance traveled in the open field test in CBA/Lac mice. This effect was receptor-specific because it was inhibited by the 5-HT2C receptor antagonist RS102221. To study the role of genotype in 5-HT2C receptor-induced hypolocomotion, locomotor activity of seven inbred mouse strains was measured after MK-212 acute treatment. We found that the 5-HT2C receptor stimulation by MK 212 decreased distance traveled in the open field test in CBA/Lac, C57Bl/6, C3H/He, and ICR mice, whereas it failed to affect locomotor activity in DBA/2J, Asn, and Balb/c mice. We also compared the interstrain differences in functional response to 5-HT2C and 5-HT2A receptors activation measured by the quantification of receptor-mediated head-twitches. These experiments revealed significant positive correlation between 5-HT2C and 5-HT2A receptors functional responses for all investigated mouse strains. Moreover, we found that 5-HT2A receptor activation with DOI did not change locomotor activity in CBA/Lac mice. Taken together, our data indicate the implication of 5-HT2C receptors in regulation of locomotor activity and suggest the shared mechanism for functional responses mediated by 5-HT2C and 5-HT2A receptors. PMID- 26380124 TI - Uncommon Cause of Trigeminal Neuralgia: Tentorial Ossification over Trigeminal Notch. AB - Ossification of the tentorium cerebelli over the trigeminal notch is rare, but it may cause compression of the trigeminal nerve, leading to trigeminal neuralgia (TN). We were unable to find any previously reported cases with radiological evaluation, although we did find one case with surgically proven ossification of the tentorium cerebelli. Here, we present a case of TN caused by tentorial ossification over the trigeminal notch depicted on magnetic resonance imaging (MRI) and computed tomography (CT). PMID- 26380125 TI - Case of Rapid Progression of Hemiatrophy on the Face: A New Clinical Entity? AB - A lot of diseases, including lupus profundus, morphea, lipodystrophy, and Parry Romberg syndrome, may manifest progressive hemifacial atrophy. These diseases usually progress slowly and rapid progression of atrophy is extremely rare. We report a case of elderly-onset rapid progression of hemifacial atrophy only in three weeks. Our case did not meet variable differential diagnoses. We discuss the clinical character of the patient against the past of literature and suppose it may be a new clinical entity. PMID- 26380123 TI - Hippocampal Infusion of Zeta Inhibitory Peptide Impairs Recent, but Not Remote, Recognition Memory in Rats. AB - Spatial memory in rodents can be erased following the infusion of zeta inhibitory peptide (ZIP) into the dorsal hippocampus via indwelling guide cannulas. It is believed that ZIP impairs spatial memory by reversing established late-phase long term potentiation (LTP). However, it is unclear whether other forms of hippocampus-dependent memory, such as recognition memory, are also supported by hippocampal LTP. In the current study, we tested recognition memory in rats following hippocampal ZIP infusion. In order to combat the limited targeting of infusions via cannula, we implemented a stereotaxic approach for infusing ZIP throughout the dorsal, intermediate, and ventral hippocampus. Rats infused with ZIP 3-7 days after training on the novel object recognition task exhibited impaired object recognition memory compared to control rats (those infused with aCSF). In contrast, rats infused with ZIP 1 month after training performed similar to control rats. The ability to form new memories after ZIP infusions remained intact. We suggest that enhanced recognition memory for recent events is supported by hippocampal LTP, which can be reversed by hippocampal ZIP infusion. PMID- 26380126 TI - Late Onset Traumatic Diaphragmatic Herniation Leading to Intestinal Obstruction and Pancreatitis: Two Separate Cases. AB - Although diaphragmatic injuries caused by blunt or penetrating trauma are rare entities, they are the most commonly misdiagnosed injuries in trauma patients and occur in approximately 3-7% of all abdominal or thoracic traumas. Acute pancreatitis secondary to late presenting diaphragmatic hernia is very rare. Here we present two separate cases: one with acute bowel obstruction and the other with acute pancreatitis secondary to late onset traumatic diaphragmatic hernia (three and twenty-eight years after chest trauma, resp.). PMID- 26380127 TI - IgG4-Seronegative Autoimmune Pancreatitis and Sclerosing Cholangitis. AB - IgG4-related disease is a relatively novel clinical entity whose gastrointestinal manifestations include type 1 autoimmune pancreatitis (AIP) and IgG4-associated sclerosing cholangitis. The presence of elevated serum IgG4 is suggestive but not essential for the diagnosis of type 1 AIP and is a pervasive feature of the proposed diagnostic criteria. The differential diagnosis of type 1 AIP includes malignant conditions, emphasizing the importance of a deliberate, comprehensive evaluation. Management of patients with a suggestive clinical presentation, but without serum IgG4 elevation, is difficult. Here we present three cases of IgG4 seronegative AIP and sclerosing cholangitis that responded to empiric steroid therapy and discuss approach considerations. These cases demonstrate the value of meticulous application of existing diagnostic algorithms to achieve a clinical diagnosis and avoid surgical intervention. PMID- 26380128 TI - B Cell Lymphoma, Unclassifiable, Transformed from Follicular Lymphoma: A Rare Presentation with Review of the Literature. AB - B cell lymphoma, unclassifiable, with features of diffuse large B cell lymphoma and classical Hodgkin's lymphoma (BCLu-DLBCL/CHL) is more commonly known as gray zone lymphoma. These cases more often present with mediastinal disease. In this report, we present a very rare case of BCLu-DLBCL/CHL without mediastinal involvement, transformed from follicular lymphoma (FL) to BCLu-DLBCL/CHL. This patient initially presented with a mass in the right neck; biopsy of the lymph node showed predominantly nodular, follicular pattern. Immunohistochemical (IHC) staining of tumor cells expressed positivity for mature B cell markers CD20, CD19, CD10, CD23, CD45, and CD38 but negative for CD5,11c. Hence, diagnosed with FL, he was given rituximab, cyclophosphamide, vincristine, and prednisone (RCVP) regimen, followed by maintenance rituximab. He showed good response. After 2 years, he presented again with a mass in the right side of the neck. Although the needle core biopsy of this mass was suggestive of B cell lymphoma, excisional biopsy showed morphological features of DLBCL as well as foci of histological pattern of CHL. IHC staining expressed positivity for CD20, CD79a, PAX5, and CD15 and CD30 consistent with DLBCL and CHL. He was diagnosed with BCLu-DLBCL/CHL. The patient received "ACVBP" (doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone) followed by radiation. BCLu-DLBCL/CHL is clinically an aggressive tumor with poorer outcomes, but our case showed complete response to ACVBP regimen with tumor regression. PMID- 26380129 TI - Fatal Case of Probable Invasive Aspergillosis after Five Years of Heart Transplant: A Case Report and Review of the Literature. AB - Invasive fungal infections are very common in solid organ transplants and occur most frequently in the first three months after transplant. A 49-year-old female with a history of two remote heart transplants with the most recent one occurring 5 years ago was admitted for increasing shortness of breath, cough, and fever. Computerized tomography (CT) scan of the chest showed left lower lung ground glass and tree-in-bud opacities. She was started on broad spectrum antibiotics along with ganciclovir and micafungin. Ganciclovir was added due to the patient's past history of CMV infection and empiric fungal coverage with micafungin. Bronchoalveolar lavage (BAL) was performed as her respiratory status worsened and voriconazole was added for possible aspergillosis in combination therapy with micafungin. BAL galactomannan returned positive which was suggestive of aspergillosis. Patient worsened clinically and subsequently succumbed to cardiorespiratory arrest despite our best efforts. It is important to have a high degree of clinical suspicion for invasive aspergillosis in transplant patients even many years after transplant and initiate aggressive therapy due to poor outcomes. PMID- 26380130 TI - Biopsy Induced Arteriovenous Fistula and Venous Stenosis in a Renal Transplant. AB - Renal transplant vein stenosis is a rare cause of allograft dysfunction. Percutaneous stenting appears to be safe and effective treatment for this condition. A 56-year-old Caucasian female with end stage renal disease received a deceased donor renal transplant. After transplant, her serum creatinine improved to a nadir of 1.2 mg/dL. During the third posttransplant month, her serum creatinine increased to 2.2 mg/dL. Renal transplant biopsy showed BK nephropathy. Mycophenolate was discontinued. Over the next 2 months, her serum creatinine crept up to 6.2 mg/dL. BK viremia improved from 36464 copies/mL to 15398 copies/mL. A renal transplant ultrasound showed lower pole arteriovenous fistula and abnormal waveforms in the renal vein. Carbon dioxide (CO2) angiography demonstrated severe stenosis of the transplant renal vein. Successful coil occlusion of fistula was performed along with angioplasty and deployment of stent in the renal transplant vein. Serum creatinine improved to 1.5 mg/dL after. PMID- 26380131 TI - Atypical Miller Fisher Syndrome with Anisocoria and Rapidly Fluctuating Pupillary Diameter. AB - Miller Fisher syndrome is a variant of Guillain-Barre syndrome characterized by the classic triad of ophthalmoplegia, ataxia, and areflexia. Pupillary involvement is common in MFS and has been reported in 35-42% of MFS patients. Although case reports have discussed isolated ophthalmoplegia as a presentation of MFS, anisocoria and rapid fluctuation of pupillary diameter have not been reported in anti-GQ1b antibody positive individuals. Here we describe an individual who presented with diplopia and was found to have progressive internal and external ophthalmoplegia with frequent fluctuations in pupillary diameter and anisocoria. These exam findings are not commonly described even in atypical presentations of MFS. The onset of symptoms was preceded by an upper respiratory infection but no gastrointestinal symptoms. Imaging and CSF studies were unremarkable; however serum levels of immunoglobulin G anti-GQ1b antibody and anti-GAD antibody were elevated confirming the diagnosis of MFS. The patient was treated with IVIG and intravenous steroids with mild resolution of external ophthalmoplegia. He did not go on to develop more typical features of MFS such as ataxia or areflexia. This demonstrates that isolated external and internal ophthalmoparesis with rapidly fluctuating pupillary diameter and associated anisocoria can be the sole manifestation of atypical MFS. PMID- 26380132 TI - Uterus Wrapping: A Novel Concept in the Management of Uterine Atony during Cesarean Delivery. AB - Uterine atony during cesarean delivery is a serious cause of maternal morbidity and mortality. Management strategies include medical treatment with uterotonic agents, manual compression of the uterus, and interventional or surgical procedures. A novel technique to compress the uterus by wrapping it with an elastic bandage and its outcome in 3 cases of uterine atony during cesarean section are presented. Our novel method of intermittent wrapping of the uterus during cesarean delivery seems to be a successful additional approach in the management of uterine atony during cesarean delivery and may be an alternative treatment option to other compressing procedures in order to avoid high blood loss and last but not least postpartum hysterectomy. PMID- 26380133 TI - Spontaneous Expulsion of Intramural Fibroid Six Weeks after Emergency Caesarean Section. AB - We present a thirty-six-year-old woman with a high risk pregnancy, complicated by multiple congenital anomalies, severe hyperemesis, a pulmonary embolus, and a large intramural fibroid. This fibroid grew in size during the pregnancy. At 34 + 5 weeks, there were reduced fetal movements and a pathological CTG. A live infant was delivered by an emergency cesarean section. Five weeks postpartum, she presented with abdominal pain, offensive vaginal discharge, and fevers. She was given antibiotics and ferrous sulphate. An abdominal ultrasound showed an 11 * 12 * 9 cm fibroid with a coarse degenerative appearance. Clinically, she showed signs of sepsis; a CT scan and laparotomy performed under general anesthetic did not find any collections as a source of sepsis. When stable, she was discharged. She re-presented two days later with a large mass (necrotic fibroid) in her vagina. This is the first case of spontaneous expulsion of fibroid six weeks after caesarean section. Presentation of pain and fever after the delivery may be due to red degeneration of the fibroid, caused by diminished blood supply, ischaemia, and necrosis. This case highlights the importance of considering fibroids as a cause for abdominal pain during and after pregnancy, even up to 6 weeks after delivery. PMID- 26380134 TI - Primary Cutaneous Peripheral T-Cell Lymphoma Not Otherwise Specified: A Rapidly Progressive Variant of Cutaneous T-Cell Lymphoma. AB - Primary Cutaneous Peripheral T-Cell Lymphoma NOS (PTL-NOS) is a rare, progressive, fatal dermatologic disease that presents with features similar to many common benign plaque-like skin conditions, making recognition of its distinguishing features critical for early diagnosis and treatment (Bolognia et al., 2008). A 78-year-old woman presented to ambulatory care with a single 5 cm nodule on her shoulder that had developed rapidly over 1-2 weeks. Examination was suspicious for malignancy and a biopsy was performed. Biopsy results demonstrated CD4 positivity, consistent with Mycosis Fungoides with coexpression of CD5, CD47, and CD7. Within three months her cancer had progressed into diffuse lesions spanning her entire body. As rapid progression is usually uncharacteristic of Mycosis Fungoides, her diagnosis was amended to PTL-NOS. Cutaneous T-Cell Lymphoma (CTCL) should be suspected in patients with patches, plaques, erythroderma, or papules that persist or multiply despite conservative treatment. Singular biopsies are often nondiagnostic, requiring a high degree of suspicion if there is deviation from the anticipated clinical course. Multiple biopsies are often necessary to make the diagnosis. Physicians caring for patients with rapidly progressive, nonspecific dermatoses with features described above should keep more uncommon forms of CTCL in mind and refer for early biopsy. PMID- 26380135 TI - Primary Mesenteric Undifferentiated Pleomorphic Sarcoma Masquerading as a Colon Carcinoma: A Case Report and Review of the Literature. AB - Undifferentiated pleomorphic sarcoma (UPS) is the most common sarcoma that appears in older patients, usually in the extremities and the retroperitoneum. Other locations are rare. By definition, in UPS, although the malignant cells tend to appear fibroblastic or myofibroblastic, they should not show differentiation towards a more specific line of differentiation. In this sense, we report the case of an 80-year-old patient with an initial clinical diagnosis of a locally advanced colonic neoplasm that was later confirmed as a primary mesenteric UPS. Primary mesenteric UPS are extremely rare with less than 20 cases reported. We also review the pathologic and radiologic diagnostic criteria and the natural history of these tumours. PMID- 26380136 TI - Systemic Chemotherapy for Progression of Brain Metastases in Extensive-Stage Small Cell Lung Cancer. AB - Lung cancer is the most common cause of cancer related mortality in men and women. Approximately 15% of lung cancers are small cell type. Chemotherapy and radiation are the mainstay treatments. Currently, the standard chemotherapy regimen includes platinum/etoposide. For extensive small cell lung cancer, irinotecan and cisplatin have also been used. Patients with relapsed small cell lung cancer have a very poor prognosis, and the morbidity increases with brain metastases. Approximately 10%-14% of small cell lung cancer patients exhibit brain metastases at the time of diagnosis, which increases to 50%-80% as the disease progresses. Mean survival with brain metastases is reported to be less than six months, thus calling for improved regimens. Here we present a case series of patients treated with irinotecan for progressive brain metastases in small cell lung cancer, which serves as a reminder of the role of systemic chemotherapy in this setting. PMID- 26380137 TI - Atraumatic Occult Odontoid Fracture in Patients with Osteoporosis-Associated Thoracic Kyphotic Deformity: Report of a Case and Review of the Literature. AB - Anderson type II odontoid fractures are reported to be the most common injury of the odontoid process in patients over the age of 65. However, atraumatic occult Anderson type III odontoid fractures have been rarely described and remain a diagnostic challenge. In the present report, we illustrate a 78-year-old female with osteoporosis-associated marked thoracic kyphotic deformity who developed atraumatic Anderson type III occult odontoid fracture and raise awareness of this condition. Anteroposterior and lateral standard radiographs of cervical spine failed to disclose odontoid fracture. Magnetic resonance imaging demonstrated intensity changes of the axis. Subsequent computed tomography clearly demonstrated Anderson type III odontoid fracture. Conservative treatment achieved complete bone union without neurological deteriorations. At 3-year follow-up, the patient was doing well without neurological and radiological deteriorations. Even if the patients have no traumatic event, we have to keep odontoid fractures in our mind as one of the differential diagnoses when we encounter elderly patients with neck pain, especially in patients with osteoporosis-associated marked thoracic kyphotic deformity. PMID- 26380138 TI - Supraspinatus Intramuscular Calcified Hematoma or Necrosis Associated with Tendon Tear. AB - Introduction. Rotator cuff intramuscular calcification is a rare condition usually caused by heterotopic ossification and myositis ossificans. Case Presentation. We describe a patient with voluminous calcified mass entrapped in supraspinatus muscle associated with corresponding tendon tear. Histological examination corresponded to a calcified hematoma or necrosis. Patient was surgically managed with open excision of the calcified hematoma and rotator cuff arthroscopic repair. At 6 months, supraspinatus muscle was healed, and functional outcome was good. Discussion and Conclusion. We hypothesized that supraspinatus intramuscular calcified hematoma was responsible for mechanical stress on the tendon. This association has never been described. PMID- 26380139 TI - Pyoderma Gangrenosum Mimicking an Infected Wound following Dynamic Hip Screw Fixation. AB - Pyoderma gangrenosum (PG) is an inflammatory ulcerative neutrophilic dermatosis that can occur following skin trauma. The correct diagnosis is not often made immediately as the condition can mimic an infective appearance. This leads to delays in the appropriate management of high dose steroids. Although debridement can offer aid in resolving lesions, this is contraindicated in the acute phase as this can cause acceleration of the pathogenic process. Biopsy of the lesion does not offer a definitive diagnosis; therefore suspicion must be maintained as the diagnosis is ultimately a clinical one. Any postoperative pustular ulcerative lesion not improving despite antibiotic therapy that also yields negative bacteriological and fungal studies should lead to consideration of this diagnosis. We document the first case of PG developing following intertrochanteric femur fracture fixation using dynamic hip screw. PMID- 26380140 TI - Aural Myiasis, a Rare Cause of Earache. AB - Myiasis of the ear is an infestation of the ear by maggots (the larval stage of flies). In the literature, there are only few cases reported about aural myiasis. It is more common to occur in tropical regions, where humidity and warm weather provide a good environment for this infestation. In this paper, a 12-year-old boy is reported to have unilateral earache for 3-day duration. Examination of the painful ear showed a tympanic membrane perforation with larvae (maggots) in the middle ear. They were removed by using a forceps and gentle irrigation of ear to expel any remnant. Further management included assessment of hearing, computed tomography (CT) scan, and outpatient follow-up. PMID- 26380141 TI - Pleuroparenchymal Fibroelastosis: A New Entity within the Spectrum of Rare Idiopathic Interstitial Pneumonias. AB - Pleuroparenchymal fibroelastosis (PPFE) is a rare entity that has been recently included in the official American Thoracic Society/European Respiratory Society (ATS/ERS) statement in 2013 as a group of rare idiopathic interstitial pneumonias (IIPs). PPFE is characterized by pleural and subpleural parenchymal thickening due to elastic fiber proliferation, mainly in the upper lobes. The etiology of the disease is unclear, although some cases have been associated as a complication after bone marrow transplantation, lung transplantation (LT), chemotherapy, and recurrent respiratory infections. The patients usually report progressive dyspnea and dry cough and are predisposed to develop spontaneous or iatrogenic pneumothoraces after surgical lung biopsy (SLB) for its diagnosis. That is why better awareness with the clinical and radiologic features can help optimal management by the multidisciplinary team. Novel invasive techniques such as cryobiopsy may become useful tools in these patients as it could spare SLB. We present the first reported cases in Spain. PMID- 26380142 TI - Postoperative Complications of Beger Procedure. AB - Introduction. Chronic pancreatitis (CP) is considered an inflammatory disease that may cause varying degrees of pancreatic dysfunction. Conservative and surgical treatment options are available depending on dysfunction severity. Presentation of Case. A 36-year-old male with history of heavy alcohol consumption and diagnosed CP underwent a duodenal-preserving pancreatic head resection (DPPHR or Beger procedure) after conservative treatment failure. Refractory pain was reported on follow-up three months after surgery and postoperative imaging uncovered stones within the main pancreatic duct and intestinal dilation. The patient was subsequently subjected to another surgical procedure and intraoperative findings included protein plugs within the main pancreatic duct and pancreaticojejunal anastomosis stricture. A V-shaped enlargement and main pancreatic duct dilation in addition to the reconstruction of the previous pancreaticojejunal anastomosis were performed. The patient recovered with no further postoperative complications in the follow-up at an outpatient clinic. Discussion. Main duct and pancreaticojejunal strictures are an unusual complication of the Beger procedure but were identified intraoperatively as the cause of patient's refractory pain and explained intraductal protein plugs accumulation. Conclusion. Patients that undergo Beger procedures should receive close outpatient clinical follow-up in order to guarantee postoperative conservative treatment success and therefore guarantee an early detection of postoperative complications. PMID- 26380143 TI - Abnormal Cystic Tumor in a Patient with Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome: Evidence of a Precursor Lesion? AB - The hereditary leiomyomatosis and renal cell cancer (HLRCC) association is a rare syndrome caused by mutation of the Kreb's cycle enzyme, fumarate hydratase (FH). It is characterized by unusually aggressive type 2 papillary renal cell histology. FH is responsible for catalyzing the conversion of fumarate to malate. Its absence leads to a state of "pseudohypoxia," inducing hypoxia inducible factor 1alpha (HIF-1alpha) and leading to increased growth factor transcription (e.g., vascular endothelial growth factor, VEGF; glucose transporter 1, GLUT1). Ultimately, this results in tumorigenesis. We present a patient who was diagnosed with HLRCC and underwent bilateral nephrectomies. One of the nephrectomy specimens was notable for benign cystic lesions that stained positive immunohistochemically for succinated proteins, a finding only noted in FH deficient cells. Thus, we posit a potential precursor lesion to type 2 papillary renal cell carcinoma in the HLRCC syndrome. PMID- 26380144 TI - Successful Use of the MYNXGRIP Closure Device during Repeated Transbrachial Percutaneous Peripheral Intervention. AB - The use of closure devices after transbrachial arterial puncture is still controversial. Here we report on a case where the MYNXGRIP (AccessClosure Inc., Santa Clara, CA, USA) could be used successfully in a patient, who underwent percutaneous peripheral arterial intervention twice via transbrachial access. PMID- 26380145 TI - Successful Implantation of a Coronary Stent Graft in a Peripheral Vessel. AB - Peripheral artery disease (PAD) is a complex, often underdiagnosed illness with rising prevalence in western world countries. During the past decade there has been a rapid advance especially in the field of endovascular treatment of PAD. Here we present for the first time a case reporting on the placement of coronary stent graft in a peripheral vessel for the management of a peripheral side branch perforation. Interventional angiologists or radiologists may consider such an option for complication management after injury of smaller vessels during peripheral percutaneous interventions. Further specialization and novel options of complication management as described in our case may shift the treatment from surgical to even more endovascular treatment procedures in the future. PMID- 26380146 TI - Relation between Apolipoprotein E Gene Polymorphism and Severity of Coronary Artery Disease in Acute Myocardial Infarction. AB - Apolipoprotein E (ApoE) is a plasma protein and associated with cholesterol transport system. In several studies, the relationship between ApoE gene polymorphism and severity of coronary artery disease (CAD) has been shown. However, the relationship between ApoE gene polymorphism and severity of CAD in patients with acute myocardial infarction (MI) has not been well known. The aim of this study is to investigate the relation between ApoE polymorphism and severity of CAD in patients with acute MI by using the Gensini Score. In this study, 138 patients were admitted to cardiology clinic with diagnosis of acute MI, and angiographic assessment was performed using the Gensini Score. Blood samples were obtained from all patients in the first day. The patients with ApoE34 genotype had high Gensini scores. Besides, the patients with E4 allele carriers were associated with high Gensini score compared with the patients without E4 allele carriers (p:0,22). The patients with E4 allele carriers were associated with higher LDL cholesterol and total cholesterol compared with the patients without E4 allele carriers (p:0,001 and p:0,03, resp.). There were no statistically significant differences between ApoE genotypes and severity of CAD by using the Gensini Score. But, the patients with E4 allele carriers were associated with high lipid levels. PMID- 26380147 TI - Early mobilization in the pediatric intensive care unit: a systematic review. AB - Children admitted to the pediatric intensive care unit (PICU) can experience significant morbidity as a consequence of mechanical ventilation and sedative medications. This morbidity could potentially be decreased with the implementation of activities to promote early mobilization during critical illness. The objective of this systematic review is to summarize the current evidence regarding rehabilitation therapies in the PICU and to highlight the knowledge gaps and avenues for future research on early mobilization in the PICU. Using a combination of controlled vocabulary and key word terms PubMed, CINAHL, and EMBASE databases were searched; no limiters were imposed on search strategies. Two reviewers abstracted data and assessed quality independently. From the 1928 articles identified in the search 168 abstracts were identified for full text review. Fifty-nine articles were chosen for data extraction and five were identified for inclusion in review. A sixth article was identified through expert clinician query. The studies were categorized into three groups based on the outcomes discussed: safety and feasibility, functional outcomes, and length of stay. A synthesis of the studies indicates that early rehabilitation in the PICU is safe and feasible with potential short and long-term benefits. Institutional, provider and patient-related barriers to initiation of early rehabilitation in the PICU are identified. Recommendations for future investigation include early rehabilitation protocols for children hospitalized in the PICU and identification of outcome measures. PMID- 26380148 TI - THE FEMALE ATHLETE TRIAD-WHAT EVERY PHYSICAL THERAPIST SHOULD KNOW. AB - Females participating in sports have the potential of developing one or multiple parts of the Female Athlete Triad, defined as the inter-relationship among energy availability, menstrual function, and bone mineral density. Energy availability, defined as dietary energy intake minus exercise energy expended, is believed to be at the cornerstone of the triad, and complications from low energy availability span many of the bodily systems and can have psychological implications. Treatment of the triad requires a comprehensive multi-disciplinary approach. Physical therapists frequently treat injured athletes and may have prolonged interactions with athletes depending on the length of the rehabilitation process. In addition to examination, assessment, and treatment of injuries, the role of the physical therapist includes prevention, and the promotion of health, wellness, and fitness. Thus, the goal of this clinical commentary is to identify and describe essential knowledge for the physical therapist, clearly identify the role of the physical therapist as part of multi disciplinary management team, and outline resources for the physical therapist and athletes relevant to the female athlete triad. LEVEL OF EVIDENCE: 5. PMID- 26380149 TI - Novel antidotes for target specific oral anticoagulants. AB - Target specific oral anticoagulants (dabigatran, rivaroxaban, apixaban, and edoxaban) are changing the landscape of anticoagulation. The major drawback is the absence of an effective antidote for severe bleedings and/or prior to procedures. Currently there are a few promising antidotes undergoing clinical trials. This review summarized the latest development in idarucizumab, andexanet alpha and PER977. PMID- 26380151 TI - CD57+ T-cells are a subpopulation of T-follicular helper cells in nodular lymphocyte predominant Hodgkin lymphoma. AB - BACKGROUND: Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is characterized by lymphocyte-predominant (LP) cells in a background of CD4+ CD57+ T-cells. These cells are normally present in the germinal center of lymphoid tissues. The cells rosetting LP cells are described to be PD-1 and BCL-6 positive, which are markers of T-follicular helper cells. This study was designed to address the question: are the CD57+ T cells in germinal centers of tonsil and NLPHL TFH cells? RESULTS: Immunohistochemistry was performed on tonsil and NLPHL. For tonsil, cells per germinal center and for NLPHL, the area around LP cells was counted. Cells rosetting LP cells were also determined. In addition, flowcytometry was performed on cell suspensions. Cells directly rosetting LP cells are positive for CD57 and/or for two markers of T-follicular helper (TFH) cells, PD-1 and BCL-6. We show that in both tonsil and NLPHL more than 90 % of CD57+ T-cells are also positive for PD-1, whereas roughly half of the PD-1+ T cells are CD57+. CD57+ cells co-express BCL-6 in tonsil and in the rosetting cells of NLPHL. CONCLUSIONS: We conclude that CD57+ T-cells are TFH cells and form a subpopulation of TFH cells in tonsils and NLPHL. PMID- 26380152 TI - Database: A New Article Type in CPT: Pharmacometrics & Systems Pharmacology. PMID- 26380150 TI - The use of erythropoiesis-stimulating agents with ruxolitinib in patients with myelofibrosis in COMFORT-II: an open-label, phase 3 study assessing efficacy and safety of ruxolitinib versus best available therapy in the treatment of myelofibrosis. AB - BACKGROUND: Anemia is considered a negative prognostic risk factor for survival in patients with myelofibrosis. Most patients with myelofibrosis are anemic, and 35-54 % present with anemia at diagnosis. Ruxolitinib, a potent inhibitor of Janus kinase (JAK) 1 and JAK2, was associated with an overall survival benefit and improvements in splenomegaly and patient-reported outcomes in patients with myelofibrosis in the two phase 3 COMFORT studies. Consistent with the ruxolitinib mechanism of action, anemia was a frequently reported adverse event. In clinical practice, anemia is sometimes managed with erythropoiesis-stimulating agents (ESAs). This post hoc analysis evaluated the safety and efficacy of concomitant ruxolitinib and ESA administration in patients enrolled in COMFORT-II, an open label, phase 3 study comparing the efficacy and safety of ruxolitinib with best available therapy for treatment of myelofibrosis. Patients were randomized (2:1) to receive ruxolitinib 15 or 20 mg twice daily or best available therapy. Spleen volume was assessed by magnetic resonance imaging or computed tomography scan. RESULTS: Thirteen of 146 ruxolitinib-treated patients had concomitant ESA administration (+ESA). The median exposure to ruxolitinib was 114 weeks in the +ESA group and 111 weeks in the overall ruxolitinib arm; the median ruxolitinib dose intensity was 33 mg/day for each group. Six weeks before the first ESA administration, 10 of the 13 patients had grade 3/4 hemoglobin abnormalities. These had improved to grade 2 in 7 of the 13 patients by 6 weeks after the first ESA administration. The rate of packed red blood cell transfusions per month within 12 weeks before and after first ESA administration remained the same in 1 patient, decreased in 2 patients, and increased in 3 patients; 7 patients remained transfusion independent. Reductions in splenomegaly were observed in 69 % of evaluable patients (9/13) following first ESA administration. CONCLUSIONS: Concomitant use of an ESA with ruxolitinib was well tolerated and did not affect the efficacy of ruxolitinib. Further investigations evaluating the effects of ESAs to alleviate anemia in ruxolitinib-treated patients are warranted (ClinicalTrials.gov identifier, NCT00934544; July 6, 2009). PMID- 26380153 TI - Modeling Suggests a Mechanism of Synergy Between Hepatitis C Virus Entry Inhibitors and Drugs of Other Classes. AB - Hepatitis C virus (HCV) entry inhibitors (EIs) act synergistically with drugs targeting other stages of the HCV lifecycle. The origin of this synergy remains unknown. Here, we argue that the synergy may arise from the complementary activities of the drugs across cell subpopulations expressing different levels of HCV entry receptors. We employ mathematical modeling of viral kinetics in vitro, where cells with a distribution of entry receptor expression levels are exposed to HCV with or without drugs. The drugs act independently in each cell, as expected in the absence of underlying interactions. Yet, at the cell population level our model predicts that the drugs exhibit synergy. EIs effectively block infection of cells with low receptor levels. With high receptor levels, where EIs are compromised, other drugs are potent. This novel mechanism of synergy, arising at the cell population level may facilitate interpretation of drug activity and treatment optimization. PMID- 26380154 TI - Population Pharmacokinetic Model Characterizing 24-Hour Variation in the Pharmacokinetics of Oral and Intravenous Midazolam in Healthy Volunteers. AB - Daily rhythms in physiology may affect the pharmacokinetics of a drug. The aim of this study was to evaluate 24-hour variation in the pharmacokinetics of the CYP3A substrate midazolam. Oral (2 mg) and intravenous (1 mg) midazolam was administered at six timepoints throughout the 24-hour period in 12 healthy volunteers. Oral bioavailability (population mean value [RSE%] of 0.28 (7.1%)) showed 24-hour variation that was best parameterized as a cosine function with an amplitude of 0.04 (17.3%) and a peak at 12:14 in the afternoon. The absorption rate constant was 1.41 (4.7%) times increased after drug administration at 14:00. Clearance (0.38 L/min (4.8%)) showed a minor 24-hour variation with an amplitude of 0.03 (14.8%) L/min and a peak at 18:50. Simulations show that dosing time minimally affects the concentration time profiles after intravenous administration, while concentrations are higher during the day compared to the night after oral dosing, reflecting considerable variation in intestinal processes. PMID- 26380156 TI - A Mixture Dose-Response Model for Identifying High-Dimensional Drug Interaction Effects on Myopathy Using Electronic Medical Record Databases. AB - Interactions between multiple drugs may yield excessive risk of adverse effects. This increased risk is not uniform for all combinations, although some combinations may have constant adverse effect risks. We developed a statistical model using medical record data to identify drug combinations that induce myopathy risk. Such combinations are revealed using a novel mixture model, comprised of a constant risk model and a dose-response risk model. The dose represents the number of drug combinations. Using an empirical Bayes estimation method, we successfully identified high-dimensional (two to six) drug combinations that are associated with excessive myopathy risk at significantly low local false-discovery rates. From the curve of a dose-response model and high dimensional drug interaction data, we observed that myopathy risk increases as the drug interaction dimension increases. This is the first time that such a dose response relationship for high-dimensional drug interactions was observed and extracted from the medical record database. PMID- 26380155 TI - Analysis of "On/Off" Kinetics of a CETP Inhibitor Using a Mechanistic Model of Lipoprotein Metabolism and Kinetics. AB - RG7232 is a potent inhibitor of cholesteryl-ester transfer protein (CETP). Daily oral administration of RG7232 produces a dose- and time-dependent increase in high-density lipoprotein-cholesterol (HDL-C) and apolipoproteinA-I (ApoA-I) levels and a corresponding decrease in low-density lipoprotein-cholesterol (LDL C) and apolipoproteinB (ApoB) levels. Due to its short plasma half-life (~3 hours), RG7232 transiently inhibits CETP activity during each dosing interval ("on/off" kinetics), as reflected by the temporal effects on HDL-C and LDL-C. The influence of RG7232 on lipid-poor ApoA-I (i.e., pre-beta 1) levels and reverse cholesterol transport rates is unclear. To investigate this, a published model of lipoprotein metabolism and kinetics was combined with a pharmacokinetic model of RG7232. After calibration and validation of the combined model, the effect of RG7232 on pre-beta 1 levels was simulated. A dose-dependent oscillation of pre beta 1, driven by the "on/off" kinetics of RG7232 was observed. The possible implications of these findings are discussed. PMID- 26380157 TI - Graphic Mining of High-Order Drug Interactions and Their Directional Effects on Myopathy Using Electronic Medical Records. AB - We propose to study a novel pharmacovigilance problem for mining directional effects of high-order drug interactions on an adverse drug event (ADE). Our goal is to estimate each individual risk of adding a new drug to an existing drug combination. In this proof-of-concept study, we analyzed a large electronic medical records database and extracted myopathy-relevant case control drug co occurrence data. We applied frequent itemset mining to discover frequent drug combinations within the extracted data, evaluated directional drug interactions related to these combinations, and identified directional drug interactions with large effect sizes. Furthermore, we developed a novel visualization method to organize multiple directional drug interaction effects depicted as a tree, to generate an intuitive graphical and visual representation of our data-mining results. This translational bioinformatics approach yields promising results, adds valuable and complementary information to the existing pharmacovigilance literature, and has the potential to impact clinical practice. PMID- 26380158 TI - Organ Impairment-Drug-Drug Interaction Database: A Tool for Evaluating the Impact of Renal or Hepatic Impairment and Pharmacologic Inhibition on the Systemic Exposure of Drugs. AB - The organ impairment and drug-drug interaction (OI-DDI) database is the first rigorously assembled database of pharmacokinetic drug exposure data from publicly available renal and hepatic impairment studies presented together with the maximum change in drug exposure from drug interaction inhibition studies. The database was used to conduct a systematic comparison of the effect of renal/hepatic impairment and pharmacologic inhibition on drug exposure. Additional applications are feasible with the public availability of this database. PMID- 26380159 TI - Impact of Kidney Function on Effects of the Dietary Approaches to Stop Hypertension (Dash) Diet. AB - OBJECTIVES: Although the Dietary Approaches to Stop Hypertension (DASH) diet lowers blood pressure in adults with hypertension, how kidney function impacts this effect is not known. We evaluated whether Estimated Glomerular Filtration Rate (eGFR) modifies the effect of the DASH diet on blood pressure, markers of mineral metabolism, and markers of kidney function. METHODS: Secondary analysis of the DASH-Sodium trial, a multicenter, randomized, controlled human feeding study that evaluated the blood pressure lowering effect of the DASH diet at three levels of sodium intake. Data from 92 participants with pre-hypertension or stage 1 hypertension during the 3450 mg /day sodium diet assignment contributed to this analysis. Stored frozen plasma and urine specimens were used to measure kidney related laboratory outcomes. RESULTS: Effects of the DASH diet on blood pressure, phosphorus, intact parathyroid hormone, creatinine, and albuminuria were not modified by baseline eGFR (mean 84.5 +/- 18.0 ml/min/1.73 m2, range 44.1 to 138.6 ml/min/1.73 m2) or the presence of chronic kidney disease (N=13%). CONCLUSIONS: The impact of the DASH diet on blood pressure, markers of mineral metabolism, and markers of kidney function does not appear to be modified by eGFR in this small subset of DASH-Sodium trial participants with relatively preserved kidney function. Whether greater reduction in eGFR modifies the effects of DASH on kidney related measures is yet to be determined. A larger study in individuals with more advanced kidney disease is needed to establish the efficacy and safety of the DASH diet in this patient population. PMID- 26380160 TI - Erratum to: The effectiveness of varicocele embolisation for the treatment of varicocele related orchalgia. AB - [This corrects the article DOI: 10.1186/s40064-015-1177-2.]. PMID- 26380162 TI - Assessing developmental toxicity of caffeine and sweeteners in medaka (Oryzias latipes). AB - The use of artificial sweeteners (ASWs) has increased and become more widespread, and consequently ASWs have appeared in aquatic environments around the world. However, their safety to the health of humans and wildlife remains inconclusive. In this study, using medaka embryos (Oryzias latipes), we investigated developmental toxicity of aspartame (ASP) and saccharin (SAC). Since ASWs are often consumed with caffeine (CAF) and CAF with sucrose (SUC), we tested biological activities of these four substances and the mixtures of CAF with each sweetener. The embryos were exposed to ASP at 0.2 and 1.0 mM, SAC at 0.005 and 0.050 mM, CAF at 0.05 and 0.5 mM, or SUC at 29 and 146 mM, starting from less than 5 h post fertilization until hatch. Control embryos were treated with embryo solution only. Several endpoints were used to evaluate embryonic development. Some of the hatchlings were also tested for anxiety-like behavior with the white preference test. The results showed that all four substances and the mixtures of CAF with the sweeteners affected development. The most sensitive endpoints were the heart rate, eye density, and hatchling body length. The hatchlings of several treatment groups also exhibited anxiety-like behavior. We then used the Integrated Biological Response (IBR) as an index to evaluate the overall developmental toxicity of the substances. We found that the ranking of developmental toxicity was SAC > CAF > ASP > SUC, and there was a cumulative effect when CAF was combined with the sweeteners. PMID- 26380161 TI - A pressure-reversible cellular mechanism of general anesthetics capable of altering a possible mechanism for consciousness. AB - Different anesthetics are known to modulate different types of membrane-bound receptors. Their common mechanism of action is expected to alter the mechanism for consciousness. Consciousness is hypothesized as the integral of all the units of internal sensations induced by reactivation of inter-postsynaptic membrane functional LINKs during mechanisms that lead to oscillating potentials. The thermodynamics of the spontaneous lateral curvature of lipid membranes induced by lipophilic anesthetics can lead to the formation of non-specific inter postsynaptic membrane functional LINKs by different mechanisms. These include direct membrane contact by excluding the inter-membrane hydrophilic region and readily reversible partial membrane hemifusion. The constant reorganization of the lipid membranes at the lateral edges of the postsynaptic terminals (dendritic spines) resulting from AMPA receptor-subunit vesicle exocytosis and endocytosis can favor the effect of anesthetic molecules on lipid membranes at this location. Induction of a large number of non-specific LINKs can alter the conformation of the integral of the units of internal sensations that maintain consciousness. Anesthetic requirement is reduced in the presence of dopamine that causes enlargement of dendritic spines. Externally applied pressure can transduce from the middle ear through the perilymph, cerebrospinal fluid, and the recently discovered glymphatic pathway to the extracellular matrix space, and finally to the paravenular space. The pressure gradient reduce solubility and displace anesthetic molecules from the membranes into the paravenular space, explaining the pressure reversal of anesthesia. Changes in membrane composition and the conversion of membrane hemifusion to fusion due to defects in the checkpoint mechanisms can lead to cytoplasmic content mixing between neurons and cause neurodegenerative changes. The common mechanism of anesthetics presented here can operate along with the known specific actions of different anesthetics. PMID- 26380163 TI - Fructose affecting morphology and inducing beta-fructofuranosidases in Penicillium janczewskii. AB - Fructose, glucose, and an equimolar mixture of both sugars affected differently hyphae thickness, biomass production and secretion of beta-fructofuranosidase in Penicillium janczewskii. Reduced growth, thinner hyphae and visible injuries were early observed during fungal cultivation in fructose-containing medium, reaching the maximum between 12 and 15 days of culture. Total sugar content from the cell wall was lower when fructose was supplied and polysaccharides lower than 10 kDa predominated, regardless the culture age. Maximal inulinase and invertase activities were detected in culture filtrates after 12 days, excepting in the glucose-containing medium. Structural changes in cell walls coincided with the increase of extracellular enzyme activity in the fructose-containing medium. The fragility of the hyphae might be related with both low carbohydrate content and predominance of low molecular weight glucans in the walls. Data presented here suggest changes in carbohydrate component of the cell walls are induced by the carbon source. PMID- 26380164 TI - Alkaline thermostable pectinase enzyme from Aspergillus niger strain MCAS2 isolated from Manaslu Conservation Area, Gorkha, Nepal. AB - Pectinase enzymes are one of the commercially important enzymes having great potential in various industries especially in food industry. Pectinases accounts for 25 % of global food enzymes produced and their market is increasing day by day. Therefore, the exploration of microorganism with novel characteristics has always been the focus of the research. Microorganism dwelling in unique habitat may possess unique characteristics. As such, a pectinase producing fungus Aspergillus niger strain MCAS2 was isolated from soil of Manaslu Conservation Area (MCA), Gorkha, Nepal. The optimum production of pectinase enzyme was observed at 48 h of fermentation. The pectinase enzyme was partially purified by cold acetone treatment followed by Sephadex G-75 gel filtration chromatography. The partially purified enzyme exhibited maximum activity 60 U/mg which was almost 8.5-fold higher than the crude pectinase. The approximate molecular weight of the enzyme was found to be 66 kDa as observed from SDS-PAGE. The pectinase enzyme was active at broad range of temperature (30-70 degrees C) and pH (6.2-9.2). Optimum temperature and pH of the pectinase enzyme were 50 degrees C and 8.2 respectively. The enzyme was stable up to 70 degrees C and about 82 % of pectinase activity was still observed at 100 degrees C. The thermostable and alkaline nature of this pectinase can meet the demand of various industrial processes like paper and pulp industry, in textile industry, fruit juice industry, plant tissue maceration and wastewater treatment. In addition, the effect of different metal ions on pectinase activity was also studied. PMID- 26380165 TI - Using eDNA to experimentally test ungulate browsing preferences. AB - Large herbivores may affect ecosystem processes and states, but such effects can be difficult to quantify, especially within multispecies assemblages. To better understand such processes and improve our predictive ability of systems undergoing change, herbivore diets can be studied using controlled feeding trials (or cafeteria tests). With some wildlife, such as large herbivores, it is impractical to empirically verify these findings, because it requires visually observing animals in forested environments, which can disturb them from their natural behaviors. Yet, in field-based cafeteria trials it is nearly impossible to differentiate selection between herbivore species that forage on similar plants and make very similar bite marks. However, during browsing ungulates leave saliva residue which includes some buccal cells and DNA that can be extracted for species identification. Here we used a newly developed eDNA-based method (biteDNA) to test the browsing preferences of four sympatric ungulate species in the wild. Overall, food preferences varied between species, but all species strongly preferred deciduous over coniferous species. Our method allows the study of plant-animal interactions in multispecies assemblages at very fine detail. PMID- 26380166 TI - Fed-batch like cultivation in a micro-bioreactor: screening conditions relevant for Escherichia coli based production processes. AB - OBJECTIVES: Recombinant protein production processes in Escherichia coli are usually operated in fed-batch mode; therefore, the elaboration of a fed-batch cultivation protocol in microtiter plates that allows for screening under production like conditions is particularly appealing. RESULTS: A highly reproducible fed-batch like microtiter plate cultivation protocol for E. coli in a micro-bioreactor system with advanced online monitoring capabilities was developed. A synthetic enzymatic glucose release medium was employed to provide carbon limited growth conditions without external substrate feed and the required buffer capacity to keep the pH value within 7 +/- 1. Accurate process design allowed for cultivation up to cell densities of 10 g biomass l(-1) without any limitations in oxygen supply [dissolved oxygen (DO) level above 30 %]. In the micro-bioreactor system (BioLector) online monitoring of cell growth, DO and pH was performed. Furthermore, the influence of the cultivation temperature, the applicability for different host strains as well as the transferability of results to lab-scale bioreactor cultivations was evaluated. CONCLUSION: This robust microtiter plate cultivation protocol allows for screening of E. coli systems under conditions comparable to lab-scale bioreactor cultivations. PMID- 26380167 TI - Post renal biopsy complication rate and diagnostic yield comparing hands free (ultrasound-assisted) and ultrasound-guided biopsy techniques of renal allografts and native kidneys. AB - BACKGROUND: Real time ultrasound guided percutaneous kidney biopsy has become the standard procedure to assess the pathology of native kidneys and renal transplants. No specific technique has shown to be totally free of post biopsy bleeding complications. Few Studies have looked at the rates of post biopsy bleeding complications comparing different needle size, post biopsy haematoma size, or clinical predictors of the complication rates. In this study we aim to assess safety and adequacy of the real time ultrasound guided biopsy using free hands (ultrasound-assisted) and ultrasound-guided technique. METHOD: The results of 527 elective native and kidney transplant biopsy performed as a day case procedure at Lancashire Teaching Hospitals were retrospectively reviewed (499 native and 28 allograft biopsies). Biopsies were grouped into 4 groups according to the technique and the needle size; group 1 (n = 119; performed by free hands ultrasound assisted- technique using 14G needle) Group 2 (n = 59; performed by free hands-ultrasound-assisted technique using 16G needle), group 3 (n = 195; performed by ultrasound-guided technique using 14G), and group 4 (n = 154; performed by ultrasound-guided technique using 16G). The 4 groups were matched in age, sex, weight, haemoglobin, serum creatinine, INR, PT, and PTT time. RESULTS: The overall tissue specimen was adequate in 80.45 % of the cases, with no difference between group 1 and 3 (81.5 and 80.52 % respectively, p = 0.82) or between group 2 and 4 (86.44 and 77.3 % respectively, p = 0.13). The overall major complications rate was 2.84 %, with no difference between group 1 and 3 (2.5 and 1 % respectively, p = 0.30) or group 2 and 4 (5 and 4.5 % respectively, p = 0.86). The overall minor complications was 3.7 % with no difference between group 2 and 4 (3.3 and 5.84 % respectively, p = 0.46), however, minor complications were higher in group 1 compared to group 3 (5.8 and 1 % respectively, p = 0.01).There was no difference between using 14G and 16G needle size in terms of tissue adequacy(p = 0.7), major complications (p = 0.2 for drop in Hb >10 g/l, p = 0.08 for blood transfusion, p = 0.35 for embolization) or minor complication items(p = 0.4 for drop in Hb, 10 g/l,p = 0.1 for haematuria, p = 0.7 for hematoma). CONCLUSION: When using a 14G needle, there is higher risk of minor complications in the free hands-(ultrasound-assisted) technique compared to the ultrasound-guided technique. There is no difference in the rates of major or minor complications between free hand and needle-guided technique using 16G needles. Both techniques showed adequate tissue sampling. PMID- 26380168 TI - Massive Bioaccumulation and Self-Assembly of Phenazine Compounds in Live Cells. AB - Clofazimine is an orally administered, FDA-approved drug that massively bioaccumulates in macrophages, forming membrane-bound intracellular structures possessing nanoscale supramolecular features. Here, a library of phenazine compounds derived from clofazimine was synthesized and tested for their ability to accumulate and form ordered molecular aggregates inside cells. Regardless of chemical structure or physicochemical properties, bioaccumulation was consistently greater in macrophages than in epithelial cells. Microscopically, some self-assembled structures exhibited a pronounced, diattenuation anisotropy signal, evident by the differential absorption of linearly polarized light, at the peak absorbance wavelength of the phenazine core. The measured anisotropy was well above the background anisotropy of endogenous cellular components, reflecting the self-assembly of condensed, insoluble complexes of ordered phenazine molecules. Chemical variations introduced at the R-imino position of the phenazine core led to idiosyncratic effects on the compounds' bioaccumulation behavior, as well as on the morphology and organization of the resulting intracellular structures. Beyond clofazimine, these results demonstrate how the self-assembly of membrane-permeant, orally-bioavailable small molecule building blocks can endow cells with unnatural structural elements possessing chemical, physical and functional characteristics unlike those of other natural cellular components. PMID- 26380169 TI - Leiomyosarcoma arising in irradiated region after breast-conserving surgery: a case report. AB - BACKGROUND: Radiation therapy (RT) is considered a risk factor for the development of sarcoma in patients with breast cancer. However, there are few reports regarding post-irradiation sarcoma (PIS). CASE PRESENTATION: The patient was a 59-year-old woman who presented with a chief complaint of induration in the lower outer quadrant of the left breast. She underwent breast-conserving surgery (BCS) for breast cancer located in the left upper inner region and received endocrine therapy following RT (50 Gy/25 fractions/5 weeks) for breast conservation 6 years previously. Core needle biopsy revealed leiomyosarcoma. There was no distant metastasis. Repeat BCS including part of the pectoralis major muscle was performed. Chest wall resection was not performed because of the lack of invasion. Based on the morphological and immunohistochemical features, a diagnosis of leiomyosarcoma was made. All of the resection margins in the specimen were tumor-free. She has been disease-free for over 20 months. CONCLUSIONS: Post-irradiation leiomyosarcoma is an extremely rare tumor with high malignant potential, and thus, multidisciplinary therapy and close follow-up are advised. PMID- 26380170 TI - Inferior vena caval thrombosis complicating pyogenic liver abscess after pancreatoduodenectomy: a case report. AB - Pyogenic liver abscess (PLA) complicated by inferior vena caval (IVC) thrombosis is rare but life-threatening. We experienced a case of PLA complicated by an IVC thrombus close to the right atrium after pancreatoduodenectomy. A 75-year-old man had undergone pancreatoduodenectomy with modified-Child reconstruction for pancreatic cancer 3 years prior, and no recurrence was noted on follow-up. He was admitted to our hospital owing to fever and general fatigue. PLA and septic shock were diagnosed, and conservative therapy with antibiotics was initiated. His general condition gradually improved, but a thrombus in the middle hepatic vein and IVC was noted on follow-up computed tomography on hospital day 8. Although anticoagulant therapy using heparin was started, the thrombus size increase and extended to the right atrium. Considering the risk of pulmonary embolism, we planned a surgical intervention with a cardiovascular surgeon to remove the thrombus. During surgery, we made an incision in the right atrium and removed the thrombus using extracorporeal circulation. After removal, we dissected the middle hepatic vein using an automated suturing device to prevent the thrombus from extending into the IVC. The patient was discharged 10 weeks after surgery. Eighteen months post-intervention, there was no recurrence of either PLA or thrombi. Our experience suggests that physicians should consider the existence of a middle hepatic vein and IVC thrombi when examining PLA patients and that surgical intervention can be applied successfully in such cases. PMID- 26380171 TI - MEISENHEIMER COMPLEX BETWEEN 2,4,6-TRINITROTOLUENE AND 3 AMINOPROPYLTRIETHOXYSILANE AND ITS USE FOR A PAPER-BASED SENSOR. AB - 2,4,6-Trinitrotoluene (TNT) forms a red-colored Meisenheimer complex with 3 aminopropyltrenthoxysilane (APTES) both in solution and on solid phase. The TNT APTES complex is unique since it forms yellow-colored complexes with 2,4,6 trinitrophenol and 4-nitrophenol, and no complex with 2,4-dinitrotoluene. The absorption spectrum of TNT-APTES has two absorption bands at 530 and 650 nm, while APTES complexes with 2,4,6-trinitrophenol and 4-nitrophenol have absorption maxima at around 420 nm, and no absorption change for 2,4-dinitrotoluene. The TNT APTES complex facilitates the exchange of the TNT-CH3 proton/deuteron with solvent molecules. The red color of TNT-APTES is immediately visible at 1 uM of TNT. PMID- 26380172 TI - Behr's Syndrome is Typically Associated with Disturbed Mitochondrial Translation and Mutations in the C12orf65 Gene. AB - BACKGROUND: Behr's syndrome is a classical phenotypic description of childhood onset optic atrophy combined with various neurological symptoms, including ophthalmoparesis, nystagmus, spastic paraparesis, ataxia, peripheral neuropathy and learning difficulties. OBJECTIVE: Here we describe 4 patients with the classical Behr's syndrome phenotype from 3 unrelated families who carry homozygous nonsense mutations in the C12orf65 gene encoding a protein involved in mitochondrial translation. METHODS: Whole exome sequencing was performed in genomic DNA and oxygen consumption was measured in patient cell lines. RESULTS: We detected 2 different homozygous C12orf65 nonsense mutations in 4 patients with a homogeneous clinical presentation matching the historical description of Behr's syndrome. The first symptom in all patients was childhood-onset optic atrophy, followed by spastic paraparesis, distal weakness, motor neuropathy and ophthalmoparesis. CONCLUSIONS: We think that C12orf65 mutations are more frequent than previously suggested and screening of this gene should be considered not only in patients with mitochondrial respiratory chain deficiencies, but also in inherited peripheral neuropathies, spastic paraplegias and ataxias, especially with pre-existing optic atrophy. PMID- 26380173 TI - Editorial preface to this special issue "Improving the quality and outcomes of lung cancer care: an interdisciplinary approach". PMID- 26380174 TI - Global trends of lung cancer mortality and smoking prevalence. AB - Lung cancer killed approximately 1,590,000 persons in 2012 and currently is the leading cause of cancer death worldwide. There is large variation in mortality rates across the world in both males and females. This variation follows trend of smoking, as tobacco smoking is responsible for the majority of lung cancer cases. In this article, we present estimated worldwide lung cancer mortality rates in 2012 using the World Health Organization (WHO) GLOBOCAN 2012 and changes in the rates during recent decades in select countries using WHO Mortality Database. We also show smoking prevalence and trends globally and at the regional level. By region, the highest lung cancer mortality rates (per 100,000) in 2012 were in Central and Eastern Europe (47.6) and Eastern Asia (44.8) among males and in Northern America (23.5) and Northern Europe (19.1) among females; the lowest rates were in sub-Saharan Africa in both males (4.4) and females (2.2). The highest smoking prevalence among males is generally in Eastern and South-Eastern Asia and Eastern Europe, and among females is in European countries, followed by Oceania and Northern and Southern America. Many countries, notably high-income countries, have seen a considerable decrease in smoking prevalence in both males and females, but in many other countries there has been little decrease or even an increase in smoking prevalence. Consequently, depending on whether or when smoking prevalence has started to decline, the lung cancer mortality trend is a mixture of decreasing, stable, or increasing. Despite major achievements in tobacco control, with current smoking patterns lung cancer will remain a major cause of death worldwide for several decades. The main priority to reduce the burden of lung cancer is to implement or enforce effective tobacco control policies in order to reduce smoking prevalence in all countries and prevent an increase in smoking in sub-Saharan Africa and women in low- and middle-income countries (LMICs). PMID- 26380175 TI - Integration of tobacco cessation services into multidisciplinary lung cancer care: rationale, state of the art, and future directions. AB - Tobacco use is the largest risk factor for lung cancer and many lung cancer patients still smoke at the time of diagnosis. Although clinical practice guidelines recommend that all patients receive evidence-based tobacco treatment, implementation of these services in oncology practices is inconsistent and inadequate. Multidisciplinary lung cancer treatment programs offer an ideal environment to optimally deliver effective smoking cessation services. This article reviews best practice recommendations and current status of tobacco treatment for oncology patients, and provides recommendations to optimize delivery of tobacco treatment in multidisciplinary practice. PMID- 26380176 TI - Implementing lung cancer screening in the real world: opportunity, challenges and solutions. AB - The World Health Organization estimates that, in 2012, there were 1,589,925 deaths from lung cancer worldwide. Screening for lung cancer with low-dose computed tomography (LDCT) has the potential to significantly alter this statistic, by identifying lung cancers in earlier stages, enabling curative treatment. Challenges remain, however, in replicating the 20% mortality benefit demonstrated by the National Lung Screening Trial (NLST), in populations outside the confines of a research trial, not only in the US but around the world. We review the history of lung cancer screening, the current evidence for LDCT screening, and the key elements needed for a successful screening program. PMID- 26380177 TI - What is quality, and can we define it in lung cancer?-the case for quality improvement. AB - Decades worth of advances in diagnostics and therapeutics are associated with only marginal improvements in survival among lung cancer patients. An obvious explanation is late stage at presentation, but gaps in the quality of care may be another reason for stifled improvements in survival rates. A framework for quality put forth by Avedis Donabedian consists of measuring structures-of-care, processes, and outcomes. Using this approach to explore for potential quality gaps, there is evidence of inexplicable variability in outcomes across patients and hospitals; variation in outcomes across differing provider types (structures of-care); and variation in approaches to staging (processes-of-care). However, this research has limitations and incontrovertible evidence of quality gaps is challenging to obtain. Other challenges to defining quality include scientific and clinical uncertainty among providers and the fact that quality is a multi dimensional construct that cannot be measured by a single metric. Nonetheless, two facts compel us to pursue quality improvement: (I) both empirically and anecdotally, actual care falls short of expected care; and (II) evidence of potential quality gaps is not ignorable primarily on ethical grounds. PMID- 26380178 TI - Measuring improvement in populations: implementing and evaluating successful change in lung cancer care. AB - Improving quality of care in lung cancer, the leading cause of cancer death worldwide and in the United States, is a major public health challenge. Such improvement requires accurate and meaningful measurement of quality of care. Preliminary indicators have been derived from clinical practice guidelines and expert opinions, but there are few standard sets of quality of care measures for lung cancer in the United States or elsewhere. Research to develop validated evidence-based quality of care measures is critical in promoting population improvement initiatives in lung cancer. Furthermore, novel research designs beyond the traditional randomized controlled trials (RCTs) are needed for wide scale applications of quality improvement and should extend into alternative designs such as quasi-experimental designs, rigorous observational studies, population modeling, and other pragmatic study designs. We discuss several study design options to aid the development of practical, actionable, and measurable quality standards for lung cancer care. We also provide examples of ongoing pragmatic studies for the dissemination and implementation of lung cancer quality improvement interventions in community settings. PMID- 26380179 TI - Lung cancer care: the impact of facilities and area measures. AB - Lung cancer is the leading cause of cancer related mortality in the US, and while treatment disparities by race and class have been well described in the literature, the impact of social determinates of health, and specific characteristics of the treatment centers have been less well characterized. As the treatment of lung cancer relies more upon a precision and personalized medicine approach, where patients obtain treatment has an impact on outcomes and could be a major factor in treatment disparities. The purpose of this manuscript is to discuss the manner in which lung cancer care can be impacted by poor access to high quality treatment centers, and how the built environment can be a mitigating factor in the pursuit of treatment equity. PMID- 26380180 TI - Lung cancer diagnosis and staging in the minimally invasive age with increasing demands for tissue analysis. AB - The diagnosis and staging of patients with lung cancer in recent decades has increasingly relied on minimally invasive tissue sampling techniques, such as endobronchial ultrasound (EBUS) or endoscopic ultrasound (EUS) needle aspiration, transbronchial biopsy, and transthoracic image guided core needle biopsy. These modalities have been shown to have low complication rates, and provide adequate cellular material for pathologic diagnosis and necessary ancillary molecular testing. As an important component to a multidisciplinary team approach in the care of patients with lung cancer, these minimally invasive modalities have proven invaluable for the rapid and safe acquisition of tissue used for the diagnosis, staging, and molecular testing of tumors to identify the best evidence based treatment plan. The continuous evolution of the field of lung cancer staging and treatment has translated into improvements in survival and quality of life for patients. Although differences in clinical practice between academic and community hospital settings still exist, improvements in physician education and training as well as adoption of technological advancements should help narrow this gap going forward. PMID- 26380181 TI - Computer modeling of lung cancer diagnosis-to-treatment process. AB - We introduce an example of a rigorous, quantitative method for quality improvement in lung cancer care-delivery. Computer process modeling methods are introduced for lung cancer diagnosis, staging and treatment selection process. Two types of process modeling techniques, discrete event simulation (DES) and analytical models, are briefly reviewed. Recent developments in DES are outlined and the necessary data and procedures to develop a DES model for lung cancer diagnosis, leading up to surgical treatment process are summarized. The analytical models include both Markov chain model and closed formulas. The Markov chain models with its application in healthcare are introduced and the approach to derive a lung cancer diagnosis process model is presented. Similarly, the procedure to derive closed formulas evaluating the diagnosis process performance is outlined. Finally, the pros and cons of these methods are discussed. PMID- 26380182 TI - Predicting the prognosis of lung cancer: the evolution of tumor, node and metastasis in the molecular age-challenges and opportunities. AB - The tumor, node and metastasis (TNM) classification of malignant tumors was proposed by Pierre Denoit in the mid-20(th) century to code the anatomic extent of tumors. Soon after, it was accepted by the Union for International Cancer Control and by the American Joint Committee on Cancer, and published in their respective staging manuals. Till 2002, the revisions of the TNM classification were based on the analyses of a database that included over 5,000 patients, and that was managed by Clifton Mountain. These patients originated from North America and almost all of them had undergone surgical treatment. To overcome these limitations, the International Association for the Study of Lung Cancer proposed the creation of an international database of lung cancer patients treated with a wider range of therapeutic modalities. The changes introduced in the 7(th) edition of the TNM classification of lung cancer, published in 2009, derived from the analysis of an international retrospective database of 81,495 patients. The revisions for the 8(th) edition, to be published in 2016, will be based on a new retrospective and prospective international database of 77,156 patients, and will mainly concern tumor size, extrathoracic metastatic disease, and stage grouping. These revisions will improve our capacity to indicate prognosis and will make the TNM classification more robust. In the future the TNM classification will be combined with non-anatomic parameters to define prognostic groups to further refine personalized prognosis. PMID- 26380183 TI - Improving lung cancer outcomes by improving the quality of surgical care. AB - Surgical resection remains the most important curative treatment modality for non small cell lung cancer, but variations in short- and long-term surgical outcomes jeopardize the benefit of surgery for certain patients, operated on by certain types of surgeons, at certain types of institutions. We discuss current understanding of surgical quality measures, and their role in promoting understanding of the causes of outcome disparities after lung cancer surgery. We also discuss the use of minimally invasive surgical resection approaches to expand the playing field for surgery in lung cancer care, and end with a discussion of the future role of surgery in a world of alternative treatment possibilities. PMID- 26380184 TI - Improving the pathologic evaluation of lung cancer resection specimens. AB - Accurate post-operative prognostication and management heavily depend on pathologic nodal stage. Patients with nodal metastasis benefit from post operative adjuvant chemotherapy, those with mediastinal nodal involvement may also benefit from adjuvant radiation therapy. However, the quality of pathologic nodal staging varies significantly, with major survival implications in large populations of patients. We describe the quality gap in pathologic nodal staging, and provide evidence of its potential reversibility by targeted corrective interventions. One intervention, designed to improve the surgical lymphadenectomy, specimen labeling, and secure transfer between the operating theatre and the pathology laboratory, involves use of pre-labeled specimen collection kits. Another intervention involves application of an improved method of gross dissection of lung resection specimens, to reduce the inadvertent loss of intrapulmonary lymph nodes to histologic examination for metastasis. These corrective interventions are the subject of a regional dissemination and implementation project in diverse healthcare systems in a tri-state region of the United States with some of the highest lung cancer incidence and mortality rates. We discuss the potential of these interventions to significantly improve the accuracy of pathologic nodal staging, risk stratification, and the quality of specimens available for development of stage-independent prognostic markers in lung cancer. PMID- 26380185 TI - Triaging early-stage lung cancer patients into non-surgical pathways: who, when, and what? AB - More lung cancer patients are being diagnosed at an earlier stage due to improved diagnostic imaging techniques, a trend that is expected to accelerate with the dissemination of lung cancer screening. Surgical resection has always been considered the standard treatment for patients with early-stage non-small cell lung cancer (NSCLC). However, non-surgical treatment options for patients with early-stage NSCLC have evolved significantly over the past decade with many new and exciting alternative treatments now available. These alternative treatments include radiofrequency ablation (RFA), microwave ablation (MWA), percutaneous cryoablation therapy (PCT), photodynamic therapy (PDT) and external beam radiation therapy (EBRT), including stereotactic body radiation therapy (SBRT) and accelerated hypofractionated radiation therapy. We describe the established alternatives to surgical resection, their advantages and disadvantages, potential complications and efficacy. We then describe the optimal treatment approach for patients with early-stage NSCLC based on tumor operability, size and location. Finally, we discuss future directions and whether any alternative therapies will challenge surgical resection as the treatment of choice for patients with operable early-stage lung cancer. PMID- 26380186 TI - Implementing effective and sustainable multidisciplinary clinical thoracic oncology programs. AB - Three models of care are described, including two models of multidisciplinary care for thoracic malignancies. The pros and cons of each model are discussed, the evidence supporting each is reviewed, and the need for more (and better) research into care delivery models is highlighted. Key stakeholders in thoracic oncology care delivery outcomes are identified, and the need to consider stakeholder perspectives in designing, validating and implementing multidisciplinary programs as a vehicle for quality improvement in thoracic oncology is emphasized. The importance of reconciling stakeholder perspectives, and identify meaningful stakeholder-relevant benchmarks is also emphasized. Metrics for measuring program implementation and overall success are proposed. PMID- 26380187 TI - 'One-stop shop': lung cancer patients' and caregivers' perceptions of multidisciplinary care in a community healthcare setting. AB - BACKGROUND: Multidisciplinary care is rarely practiced in community healthcare settings where the majority of patients receive lung cancer care in the US. We sought direct input from patients and their informal caregivers on their experience of lung cancer care delivery. METHODS: We conducted focus groups of patient and caregiver dyads. Patients had received care for lung cancer in or out of a multidisciplinary thoracic oncology clinic coordinated by a nurse navigator. Focus groups were audiotaped, transcribed, and analyzed using Creswell's 7-step process. Recurring overlapping themes were developed using constant comparative methods within the Grounded Theory framework. RESULTS: A total of 46 participants were interviewed in focus groups of 5 patient-caregiver dyads. Overlapping themes were a perception that multidisciplinary care improved physician collaboration, patient-physician communication, and patient convenience, while reducing redundancy in testing. Improved coordination decreased confusion, stress, and anxiety. Negative experience of serial care included poor communication among physicians, insensitive communication about illness, delays in diagnosis and treatment, misdiagnosis, and mistreatment. Physician-to-physician communication and patient education were suggested areas for improvement in the multidisciplinary model. CONCLUSIONS: Multidisciplinary care was perceived as more patient-centered, effective, safe, and efficient than standard serial care. It was also believed to improve the timeliness of care and equitable access to high quality care. Additional studies to compare these perspectives to those of other key stakeholders, including clinicians, hospital administrators and representatives of third party payers, will facilitate better understanding of the role of multidisciplinary care programs in lung cancer care delivery. PMID- 26380189 TI - Exploring controversies in lung cancer using structured pro-con debates. PMID- 26380188 TI - Erlotinib therapy after initial platinum doublet therapy in patients with EGFR wild type non-small cell lung cancer: results of a combined patient-level analysis of the NCIC CTG BR.21 and SATURN trials. AB - BACKGROUND: The clinical benefit of erlotinib in treating epidermal growth factor receptor (EGFR) wildtype non-small cell lung cancer (NSCLC) has been questioned. We examined the impact of erlotinib in confirmed EGFR wildtype patients in two placebo-controlled phase III trials: the National Cancer Institute of Canada Clinical Trials Group BR.21 (BR.21) and Sequential Tarceva in Unresectable Non Small Cell Lung Cancer (SATURN) trials. METHODS: Combined re-analysis of progression-free survival (PFS) and overall survival (OS) in patients with known wildtype EGFR, estimated by Kaplan-Meier curves and compared by two-sided log rank test. Cox proportional hazards model was used to estimate hazard ratios (HR) adjusted for potential confounders. Additional analyses assessed comparability of patients with known and unknown EGFR mutation status to determine generalizability of the two study populations. RESULTS: Mutation status was known in 25% (n=184 of 731) of the BR.21, and 49% (n=437 of 889) of the SATURN populations, of which 82% (n=150) and 89% (n=388) respectively had wildtype EGFR. HR for PFS was 0.71 (95% CI, 0.59-0.85; P<0.01) and for OS was 0.72 (95% CI, 0.59 0.88; P<0.01). Baseline characteristics and outcome (PFS and OS) distributions were similar for patients with known and unknown EGFR status, suggesting generalizability of the EGFR wildtype data. Erlotinib benefit was sustained in all clinical subsets. CONCLUSIONS: Erlotinib provided a consistent and significant improvement in survival for patients with EGFR wildtype NSCLC in both studies, individually and in combination. The benefit of erlotinib does not appear to be limited to patients with activating mutations of EGFR. PMID- 26380190 TI - Pros: long-term CT scan follow-up should be the standard of care in patients who are curatively treated for an early-stage non-small cell lung cancer. PMID- 26380191 TI - Cons: long-term CT-scan follow-up is not the standard of care in patients curatively treated for an early stage non-small cell lung cancer. PMID- 26380192 TI - Rebuttal from Dr Hanna. PMID- 26380193 TI - Rebuttal from Dr van Meerbeeck. PMID- 26380194 TI - A meta-analysis of safety and efficacy on first-line S-1 therapy in cancer patients. AB - BACKGROUND: The incidence of grade 3/4 adverse effects due to S-1 therapy and the efficacy of S-1-based therapy vs. S-1 monotherapy have not been well described. We conducted an updated meta-analysis to evaluate this problem. METHODS: We searched the electronic databases, including PubMed, Embase, and Cochrane database to investigate the effects of phase 2 and 3 prospective clinical trials on first-line S-1 therapy in cancer patients. Data from included studies were pooled using Stata version 12.0. RESULTS: Twenty eight studies were included. First-line S-1 monotherapy showed low incidence of grade 3/4 adverse effects. And the highest rate grade 3/4 hematological event was neutropenia [7%, 95% confidence interval (CI): 5-8%]; the highest rate grade 3/4 non-hematological event was anorexia (7%, 95% CI: 6-9%). Longer overall survival (OS) time and progression-free survival (PFS) time was exhibited in S-1-based therapy, compared with S-1 monotherapy [hazard ratio (HR) 0.836, 95% CI: 0.761-0.911, P=0.000, and HR 0.650, 95% CI: 0.540-0.759, P=0.000, respectively]. However, the incidence of grade 3/4 adverse effects was also higher in S-1-based therapy than S-1 monotherapy in cancer patients, with relative risk (RR) of neutropenia and anorexia were respectively 4.62 (95% CI: 2.92-7.30) and 1.46 (95% CI: 0.84-2.55). CONCLUSIONS: S-1 monotherapy was demonstrated with low incidence of high grade adverse effects, therefore it is well tolerated for majority cancer patients; S-1 based therapy significantly improved OS and PFS compared with S-1 monotherapy, with an increased risk of high grade adverse effects. PMID- 26380195 TI - Professor Caicun Zhou: a successful step forward for international exchange on combating lung cancer. PMID- 26380196 TI - Pediatric primary urolithiasis: Symptoms, medical management and prevention strategies. AB - In the past few decades pediatric urolithiasis has become more frequent. The reason for this increase is not completely clear but has been attributed to changes in climate, nutritional habits and possibly other environmental factors. Although less frequent than adult stone disease, urolithiasis in the pediatric age group is also related to significant morbidity, particularly since stones tend to recur, and, thus, should not be underestimated. Most children with idiopathic stone disease have an underlying metabolic abnormality substantiating the importance of metabolic evaluation already following initial diagnosis of urolithiasis. Identification of the metabolic abnormality allows for more specific prescription of non pharmacological and pharmacological interventions aimed at preventing recurrent stone formation. A better understanding of the causes of kidney stone disease will provide better strategies for stone prevention in children. PMID- 26380197 TI - Update on immunoglobulin A nephropathy, Part I: Pathophysiology. AB - Immunoglobulin A (IgA) nephropathy is one of the most common glomerulonephritis and its frequency is probably underestimated because in most patients the disease has an indolent course and the kidney biopsy is essential for the diagnosis. In the last years its pathogenesis has been better identified even if still now several questions remain to be answered. The genetic wide association studies have allowed to identifying the relevance of genetics and several putative genes have been identified. The genetics has also allowed explaining why some ancestral groups are affected with higher frequency. To date is clear that IgA nephropathy is related to auto antibodies against immunoglobulin A1 (IgA1) with poor O glycosylation. The role of mucosal infections is confirmed, but which are the pathogens involved and which is the role of Toll-like receptor polymorphism is less clear. Similarly to date whether the disease is due to the circulating immunocomplexes deposition on the mesangium or whether the antigen is already present on the mesangial cell as a "lanthanic" deposition remains to be clarified. Finally also the link between the mesangial and the podocyte injury and the tubulointerstitial scarring, as well as the mechanisms involved need to be better clarified. PMID- 26380198 TI - Current management of autosomal dominant polycystic kidney disease. AB - Autosomal dominant polycystic kidney disease (ADPKD), the most frequent cause of genetic renal disease affecting approximately 4 to 7 million individuals worldwide and accounting for 7%-15% of patients on renal replacement therapy, is a systemic disorder mainly involving the kidney but cysts can also occur in other organs such as the liver, pancreas, arachnoid membrane and seminal vesicles. Though computed tomography and magnetic resonance imaging (MRI) were similar in evaluating 81% of cystic lesions of the kidney, MRI may depict septa, wall thickening or enhancement leading to upgrade in cyst classification that can affect management. A screening strategy for intracranial aneurysms would provide 1.0 additional year of life without neurological disability to a 20-year-old patient with ADPKD and reduce the financial impact on society of the disease. Current treatment strategies include reducing: cyclic adenosine monophosphate levels, cell proliferation and fluid secretion. Several randomised clinical trials (RCT) including mammalian target of rapamycin inhibitors, somatostatin analogues and a vasopressin V2 receptor antagonist have been performed to study the effect of diverse drugs on growth of renal and hepatic cysts, and on deterioration of renal function. Prophylactic native nephrectomy is indicated in patients with a history of cyst infection or recurrent haemorrhage or to those in whom space must be made to implant the graft. The absence of large RCT on various aspects of the disease and its treatment leaves considerable uncertainty and ambiguity in many aspects of ADPKD patient care as it relates to end stage renal disease (ESRD). The outlook of patients with ADPKD is improving and is in fact much better than that for patients in ESRD due to other causes. This review highlights the need for well-structured RCTs as a first step towards trying newer interventions so as to develop updated clinical management guidelines. PMID- 26380199 TI - Project-based faculty development: Indian perspectives. PMID- 26380200 TI - Implementation of cardiopulmonary resuscitation workshop in first MBBS. AB - CONTEXT: Students should be exposed to early clinical scenario so that they start developing competency-based learning right from their MBBS 1(st) year. Medical Council of India has recognized this need and has suggested early clinical exposure of MBBS 1(st) year students in their document Vision 2015. Medical education in India needs change for achieving desired competencies. It has been concluded that Indian medical undergraduates have inadequate knowledge in cardiopulmonary resuscitation (CPR). AIMS: To implement CPR workshop in MBBS 1(st) year, and to study the impact of CPR workshop among MBBS 1(st) year students. DESIGN: Interventional study. MATERIALS AND METHODS: CPR workshop was conducted with the help of Faculty of Anesthesia and Physiology among MBBS 1(st) year students. Teaching learning methods employed were lecture, demonstration, and hand-on practice on mannequin in small groups. The evaluation was done by pre and post-standardized, validated questionnaire; direct observation procedural skill, and feedback questionnaire. RESULTS: There was a significant improvement in knowledge of students as shown from results of pre- and post-questionnaire. About 84.24% students found the presentation excellent, 71.23% students found the demonstration excellent in terms of visibility and clarity, 63.7% students found the instructions excellent. All students were successful in acquiring skills of CPR as shown by results of directly observed procedural skills. CONCLUSIONS: Results of this study suggest that the workshop provided students with sound basic knowledge and adequate practical skills in CPR. CPR workshop should be carried out every year among undergraduate students. CPR workshop should be introduced in MBBS 1(st) year curriculum. PMID- 26380201 TI - Involving postgraduate's students in undergraduate small group teaching promotes active learning in both. AB - BACKGROUND: Lecture is a common traditional method for teaching, but it may not stimulate higher order thinking and students may also be hesitant to express and interact. The postgraduate (PG) students are less involved with undergraduate (UG) teaching. Team based small group active learning method can contribute to better learning experience. AIM: To-promote active learning skills among the UG students using small group teaching methods involving PG students as facilitators to impart hands-on supervised training in teaching and managerial skills. METHODOLOGY: After Institutional approval under faculty supervision 92 UGs and 8 PGs participated in 6 small group sessions utilizing the jigsaw technique. Feedback was collected from both. OBSERVATIONS: Undergraduate Feedback (Percentage of Students Agreed): Learning in small groups was a good experience as it helped in better understanding of the subject (72%), students explored multiple reading resources (79%), they were actively involved in self-learning (88%), students reported initial apprehension of performance (71%), identified their learning gaps (86%), team enhanced their learning process (71%), informal learning in place of lecture was a welcome change (86%), it improved their communication skills (82%), small group learning can be useful for future self learning (75%). Postgraduate Feedback: Majority performed facilitation for first time, perceived their performance as good (75%), it was helpful in self-learning (100%), felt confident of managing students in small groups (100%), as facilitator they improved their teaching skills, found it more useful and better identified own learning gaps (87.5%). CONCLUSIONS: Learning in small groups adopting team based approach involving both UGs and PGs promoted active learning in both and enhanced the teaching skills of the PGs. PMID- 26380202 TI - Small group discussion: Students perspectives. AB - CONTEXT: Various alternative methods are being used in many medical colleges to reinforce didactic lectures in physiology. Small group teaching can take on a variety of different tasks such as problem-solving, role play, discussions, brainstorming, and debate. Research has demonstrated that group discussion promotes greater synthesis and retention of materials. AIMS: The aims of this study were to adopt a problem-solving approach by relating basic sciences with the clinical scenario through self-learning. To develop soft skills, to understand principles of group dynamics, and adopt a new teaching learning methodology. SUBJECTS AND METHODS: Experimental study design was conducted in Phase I 1(st) year medical students of 2014-2015 batch (n = 120). On the day of the session, the students were grouped into small groups (15 each). The session started with the facilitator starting off the discussion. Feedback forms from five students in each group was taken (n = 40). A five point Likert scale was used ranging from strongly agree to strongly disagree. Data were analyzed using IBM SPSS Statistics for Windows, Version 21.0. Armonk, NY: IBM Corp. RESULTS: Our results show that 70% of the students opined that small group discussion were interactive, friendly, innovative, built interaction between teacher and student. Small group discussion increased their thought process and helped them in better communication. CONCLUSIONS: The small group discussion was interactive, friendly, and bridged the gap between the teacher and student. The student's communication skills are also improved. In conclusion, small group discussion is more effective than the traditional teaching methods. PMID- 26380203 TI - Case-based learning in pharmacology: Moving from teaching to learning. AB - CONTEXT: The knowledge of pharmacology is an important necessity for the prevention and treatment of diseases. The study aimed to find out the beneficial effects of case-based learning (CBL) compare to didactic lecture in pharmacology and to evaluate the perceptions of students regarding the CBL. METHODS: A total of 68 students took part in the study and were randomly assigned to two equal groups: Group 1 (CBL group) and Group 2 (lecture group). Cases, test items, students feedback questionnaires were developed and peer viewed by experts. Group 1 underwent the CBL and the same topics were handled as a didactic lecture in Group 2 concurrently. Written tests were conducted after completion of each session and the perceptions of students were evaluated. RESULTS: The Group 1 showed significantly increased (P < 0.001) test score in knowledge-based and critical thinking (clinical application) as compared to Group 2. The perceptions of students were quite positive regarding the CBL as a majority revealed that they has better understanding of concepts (82.35%), self-learning approach (91.17%), critical thinking with integration clinical subjects (97.05%), and active participation in discussion (76.47%) as well as interest in subject (88.24%) through the CBL process. CONCLUSION: Self-learning approach, critical thinking with the integration of subject, and arousal of interest in the subject were positive effects of CBL in the teaching of concepts of pharmacology. PMID- 26380204 TI - Integrated teaching program using case-based learning. AB - BACKGROUND: At present, in a medical school, students are taught in different departments, subject-wise, without integration to interrelate or unify subjects and these results in compartmentalization of medical education, with no stress on case-based learning. Therefore, an effort was made to develop and adopt integrated teaching in order to have a better contextual knowledge among students. METHODOLOGY AND IMPLEMENTATION: After the faculty orientation training, four "topic committees" with faculty members from different departments were constituted which decided and agreed on the content material to be taught, different methodologies to be used, along with the logical sequencing of the same for the purpose of implementation. Different teaching methodologies used, during the program, were didactic lectures, case stimulated sessions, clinical visits, laboratory work, and small group student's seminar. RESULTS: After the implementation of program, the comparison between two batches as well as between topics taught with integrated learning program versus traditional method showed that students performed better in the topics, taught with integrated approach. Students rated "clinical visits" as very good methodology, followed by "case stimulated interactive sessions." Students believed that they felt more actively involved, and their queries are better addressed with such interactive sessions. CONCLUSION: There is a very good perception of students toward integrated teaching. Students performed better if they are taught using this technique. Although majority of faculty found integrated teaching, as useful method of teaching, nevertheless extra work burden and interdepartmental coordination remained a challenging task. PMID- 26380205 TI - Effectiveness of skeleton handouts during ophthalmology theory lectures for undergraduate medical students. AB - BACKGROUND: Although lecture handouts are commonly given to students during theory lectures, students' perception, as well as their performance, can vary depending on the type of handouts they receive for information processing. METHODOLOGY: This is a quasi-experimental study involving 6(th) semester medical students. The study was conducted during theory lectures on ophthalmology. The two types of notes given to the students were comprehensive handout and a skeleton handout, which included some lecture notes but required substantial annotation by the students. Pre-test and post-test in the form of multiple choice questions were conducted before and after the lecture session, respectively. RESULTS: There was a significant difference of mean score of pre- and post-test between skeletal handout (pre = 1.85 +/- 1.275, post = 4.85 +/- 0.363) and full handout (pre = 1.92 +/- 1.09 post = 2.61 +/- 0.771) with P < 0.001. However, the students' responses to questionnaires indicated a strong preference for much detailed handouts as essential to preparation for examinations. CONCLUSION: The student can improve their performance during examination while working on skeletal handouts during theory lectures in spite of showing a preference for complete handouts. PMID- 26380206 TI - Assessment of the acceptance and effectiveness of peer-assisted learning in pediatrics. AB - BACKGROUND: Peer-assisted learning (PAL) is the development of knowledge and skill through active help and support of equals. However, this has not been tested in medical education in India. OBJECTIVES: To assess the effectiveness of PAL on improvement in cognitive assessment scores and its acceptance among undergraduate medical students in one public teaching medical university in North India. METHODOLOGY: After approval from the Institutional Ethics Committee, three PAL sessions, 1 per week, each on specific topic, were conducted using small group discussion methodology with a faculty contact and student leader and 4-6 peer-learners, in 9(th) semester MBBS students. A pretest with multiple choice questions (MCQs) was followed by distribution of learning objectives and list of resource material. PAL session was conducted after 72 h, followed by posttest by MCQs and then focus group discussion (FGD) on students' experiences. RESULTS: Of the 26 students enrolled, three PAL sessions was completed by 22 (84.6%) students. The correlation coefficient between pre- and post-test scores was 0.48 (P < 0.0001), with a 24.2% improvement in posttest scores. In the nine FGDs most said that PALs helped in the better preparation of the topic, clarifying doubts, lessened examination anxiety, improved communication skills, and increased self confidence. CONCLUSION: PAL was well accepted, and it improved assessment scores. Therefore, it can be adopted for teaching selected topics across all subjects of MBBS course. PMID- 26380207 TI - The usefulness of Mini Clinical Evaluation Exercise as a learning tool in different pediatric clinical settings. AB - BACKGROUND: Mini Clinical Evaluation Exercise (Mini-CEX), have been an underutilized tool for the formative assessment in India. Not many studies have been done in India to examine its feasibility and acceptability in residency programs of most clinical subjects. AIM: To assess the feasibility and acceptability of Mini-CEX in different pediatric clinical settings and to know if it helped the residents with improved learning. METHODS: Pediatric residents were regularly evaluated with Mini-CEX over a period of 1 year by standard methodology. Each encounter was followed by case specific feedback given to the residents. Several such encounters were held in different pediatric clinical settings like pediatric outpatient departments (POPDs), pediatric wards, Pediatric Intensive Care Unit (PICU), Neonatal Intensive Care Unit (NICU), etc. By the end of the year, both teachers and residents were asked to give feedback on 5 point Likert scale based on their experience with the exercise. RESULTS: The entire exercise was participated by 11 teachers and 23 residents. Mini-CEX encounters were conducted in POPDs 38%, pediatrics ward 22%, PICU 19%, NICU 15%, and casualty 6%. The overall average score for all students was 5.65. An average improvement in scores by 1.9 points was observed over a period of 1 year all students and teachers felt that the exercise was feasible in most pediatric clinical settings. Students accepted that the feedback given by the teachers well and accepted that this feedback helped them with improved learning. CONCLUSIONS: Residents and teachers, both considered Mini-CEX as a feasible exercise. Residents accepted that the feedback after each exercise helped them in their learning. PMID- 26380208 TI - Comparison of two formats for student evaluation of teacher effectiveness. AB - CONTEXT: Student evaluation of faculty is an essential part of the academic process. The study was designed to compare two formats of student evaluation of teachers (SETs) with a view to determine the method with minimum bias. AIMS: To compare student ratings of teacher effectiveness obtained from two different SET formats and determine factors contributing to the student bias. MATERIALS AND METHODS: Faculty members of first professional were evaluated by MBBS students using a SET-I questionnaire already in use. Faculty perceived types of bias were documented using a separate semi-structured questionnaire. Based on this, a second SET-II questionnaire with Likert scale was designed and filled out by the same students as before. The faculty was apprised of the scores granted to them, and their acceptance of the preferred SET format was determined with the help of another questionnaire. RESULTS: Ratings obtained from 71 students using both the SET-I and SET-II formats showed no difference. However, the level of students satisfaction with teacher effectiveness, compared with the total teacher score, indicated that when a score of the faculty was below 50%, the level of students satisfaction reduced considerably. The major causes of perceived negative bias identified were strictness, seniority, gender, classes taken, less interest in the subject, and lower student grades. SET-II was preferred by faculty but didn't eliminate all bias factors. CONCLUSIONS: Although it was not possible to remove all causes of bias from the modified student questionnaire, the faculty perception of bias affecting the students rating seems to be largely ungrounded as there was no difference between the scores obtained. PMID- 26380209 TI - To design and implement a prescription writing teaching module for second professional medical students. AB - CONTEXT: There is ample evidence to prove that medical graduates are not prescribing rationally and this can be improved by proper training. AIMS: To design and implement a prescription writing teaching module for second professional medical students. SUBJECTS AND METHODS: A module of 3 h duration consisting of didactic lecture, interactive audiovisual small group session, and evaluation method was framed for every disease and implemented. Completeness of the prescriptions was evaluated on a scale of 1-4. Appropriateness of the prescription, knowledge about the rationale behind the drugs used and adverse events related to the drugs used was judged in three categories, that is, appropriate and complete; appropriate but insufficient; and inappropriate. RESULTS: One thousand six hundred and seven response sheets to 24 health problems were collected. Completeness score of 18% was 2, 59% was 3% and 24% was 4.41% prescriptions were appropriate and complete, 58% appropriate but insufficient and 1% inappropriate. The rationale behind the drugs used was appropriate and complete 24%, appropriate but insufficient 68%, inappropriate 8%. Documentation of adverse events was appropriate and complete 23%, appropriate but insufficient 49%, inappropriate 28%. All facilitators were satisfied with the duration, contents and conduct of the sessions. CONCLUSIONS: A module is an effective tool for teaching prescription writing to undergraduate students; modifications required in contents and strategy to emphasize the need of complete documentation. PMID- 26380211 TI - Introduction of problem-based learning in undergraduate dentistry program in Nepal. AB - CONTEXT: Problem-based learning (PBL) is a methodology widely used in medical education and is growing in dental education. Initiation of new ideas and teaching methods requires a change in perception from faculty and institute management. Student-centered education is a need of the day and PBL provides the best outlet to it. AIM: To introduce PBL, assess feasibility and challenges in undergraduate dentistry program and evaluate the impact on their learning. SETTINGS AND DESIGN: PBL was used as a teaching methodology on 37 students in 2(nd) year BDS program. The PBL was duplicated as that of MBBS program. PBL was spread over 5 days. Pre- and post-test questions along with different questionnaires were designed for the students and tutors/faculty to be administered after PBL session. SUBJECTS AND METHODS: Case with temporomandibular joint and muscles of mastication and occlusion was designed as a module with five triggers given to students who were divided into five groups over two tutorials facilitated by tutor. Resource sessions were held by involved departments (Oral Biology, Oral Pathology, Oral Medicine and Radiology, Orthodontics, and Oral Surgery). Students were allotted time for search, research and discover to search literature. STATISTICAL ANALYSIS USED: Descriptive statistics. RESULTS: Pre and post-test comparison showed that the knowledge increased immensely following PBL sessions. Students' assessment by tutors following two PBL tutorials showed a mean score of 34.9 +/- 4.01 and 35.5 +/- 3.86, respectively. Students' feedback showed that most of them preferred PBL because they found it interactive, collaborative, goal and research oriented. Students were motivated to learn new topic because learning objectives were formulated by themselves and they developed self-directed learning skills. The tutors learned to design cases. CONCLUSIONS: PBL encouraged students to use more interactive methods of learning which possibly will make them lifelong learners. PMID- 26380210 TI - Teaching communications skills to medical students: Introducing the fine art of medical practice. AB - INTRODUCTION: Like many other people based professions, communications skills are essential to medical practice also. Traditional medical teaching in India does not address communication skills which are most essential in dealing with patients. Communication skills can be taught to medical students to increase clinical competence. OBJECTIVE: To teach basic communication and counseling skills to fourth-year undergraduate students to increase their clinical competence. METHODOLOGY: A total of 48, fourth-year MBBS students participated in the study. They were given training in basic communication and counseling skills and taught the patient interview technique according to Calgary-Cambridge guide format. Improvement in communication was assessed by change in pre- and post training multiple choice questions, clinical patient examination, and Standardized Patient Satisfaction Questionnaire (SPSQ) scores. RESULTS AND ANALYSIS: About 88% of the students in the sample were convinced of the importance of learning communication skills for effective practice. Almost 90% students were communicating better after training, as tested by improved SPSQ. As judged by Communication Skill Attitude Scale, student's positive attitude toward learning communication skill indicated that there is a necessity of communication skill training during undergraduate years. CONCLUSION: The ability to communicate effectively is a core competency for medical practitioners. Inculcating habits of good communications skill during formative years will help the medical students and future practitioners. Regular courses on effective communication should be included in the medical school curriculum. PMID- 26380212 TI - Evaluation of orientation program for fresh MBBS entrants: Faculty and students' perspectives. AB - CONTEXT: One-day orientation program (OP) for fresh MBBS entrants is running in our institute since 2010, but has never been evaluated. AIMS AND OBJECTIVES: To evaluate the OP from students' and faculty perspectives and to recommend a revised program. METHODOLOGY: Totally 439 students of three MBBS batches were enrolled in the study. Students were asked to fill an anonymous semi-structured, pretested questionnaire. Views of faculty members were recorded by conducting three focus group discussions. RESULTS: More than half of the students have never attended the institutional OP due to timings issue. Overall rating of the program was good, but many students and faculty members suggested changes in the duration, timings and course content of the OP. A revised OP was proposed to the authorities. CONCLUSION: The current institutional program though rated good, requires a lot of amendments. The revised proposed OP should be implemented from the coming session. PMID- 26380213 TI - Educational interventions to improve knowledge and skills of interns towards prevention and control of hospital-associated infections. AB - CONTEXT: We believe that there is significant educational deficit amongst interns regarding up-to-date formal knowledge and skills on healthcare-associated infections (HAIs) which might compromise patient safety. This urgently requires curriculum innovations to ensure their formal training on HAIs prevention and control. AIM: Education of interns to improve their knowledge and skills toward HAIs prevention and control. SUBJECTS AND METHODS: This pilot study was conducted in interns using a multimodal approach consisting of a combination of videos, PowerPoint presentation, and hands-on demonstration to provide applied and practical teaching on prevention and control of HAIs. Pre- and post-test assessment of knowledge, attitude, and skills was carried out by multiple choice questions, 5-point Likert scale, and Objective Structured Practical Examination respectively. STATISTICAL ANALYSIS USED: Paired t-test. RESULTS: A statistically significant improvement in the overall score rates between pre- and post-test of intern's was seen, suggesting that educational programs have a positive effect. Intern's felt benefitted from interventions focused on HAIs prevention and control and hoped that such sessions are integrated in the regular undergraduate curriculum. A majority of the students felt that their learning style assessment matched well with their own perception of learning preference. CONCLUSIONS: Assessment drives learning; hence strengthening the contribution of health-care workers to HAIs prevention programs should include measures that enhance knowledge, improve skills and develop appropriate attitudes, resulting in safety and quality of patient care. PMID- 26380214 TI - Students awareness of learning styles and their perceptions to a mixed method approach for learning. AB - BACKGROUND: Individualization of instructional method does not contribute significantly to learning outcomes although it is known that students have differing learning styles (LSs). Hence, in order to maximally enhance learning, one must try to use a mixed method approach. HYPOTHESIS: Our hypothesis was that awareness of preferred LS and motivation to incorporate multiple learning strategies might enhance learning outcomes. AIM: Our aim was to determine the impact of awareness of LS among medical undergraduates and motivating students to use mixed methods of learning. MATERIALS AND METHODS: Before awareness lecture, LS preferences were determined using Visual, Aural, Read/Write, and Kinesthetic (VARK) questionnaire. Awareness of LS was assessed using a validated questionnaire. Through a lecture, students were oriented to various LSs, impact of LS on their performance, and benefit of using mixed method approach for learning. Subsequently, group discussions were organized. After 3 months, VARK preferences and awareness of LSs were reassessed. Student narratives were collected. Qualitative analysis of the data was done. RESULTS: There was a significant increase in the number of students who were aware of LS. The number of participants showing a change in VARK scores for various modalities of learning was also significant (P < 0.001). CONCLUSION: Thus, awareness of LSs motivated students to adapt other learning strategies and use mixed methods for learning. PMID- 26380215 TI - Formative assessment in postgraduate medical education - Perceptions of students and teachers. AB - CONTEXT: One of the most important factors of medical education that can revolutionize the learning process in postgraduate students (PGs) is assessment for learning by means of formative assessment (FA). FA is directed at steering and fostering learning of the students by providing feedback to the learner. However, though theoretically well suited to postgraduate training, evidence are emerging that engaging stakeholders in FA in daily clinical practice is quite complex. AIMS: To explore perceptions of PGs and teachers (Ts) about factors that determines active engagement in FA. SUBJECTS AND METHODS: It was a descriptive qualitative study involving focus group discussions (FGDs) with PGs and Ts from Departments of Pediatrics and Orthopedics. FGDs data were processed through points/remarks, data reduction, data display, coding followed by theme generation for content analysis. RESULTS: Four higher order themes emerged: Harsh reality of present summative assessment structure, individual perspectives on feedback, supportiveness of the learning environment, and the credibility of feedback and/or feedback giver. CONCLUSIONS: Engaging in FA with a genuine impact on learning is complex and quite a challenge to both students and Ts. Increased acceptability along with the effective implementation of FA structure, individual perspectives on feedback, a supportive learning environment and credibility of feedback are all important in this process. Every one of these should be taken into account when the utility of FA in postgraduate medical training is evaluated. PMID- 26380216 TI - Implementation of an education development project in pathology to improve student competency-lessons learnt. AB - CONTEXT: Basic medical sciences and clinical teachings are not coordinated in the present medical education system. They are not taught keeping in mind the outcomes required at the time of actual handling of patients in the community. AIMS: An educational development project was implemented in the Department of Pathology with the aim that it will result in the student learning to link the pathophysiology of the disease to clinical scenarios and become fully competent for lifelong medical practice. SUBJECTS AND METHODS: The pathology teaching of the second professional batch was modified by starting with defining the desired outcomes/competencies in the student's knowledge, skills, and attitude which were then addressed by lectures, demonstrations, practical classes and small group activities where case scenarios and laboratory reports were included. The outcome was assessed by Objectively Structured Clinical/Practical Examination and multiple choice questions. Force field analysis, faculty and student interviews, and questionnaires were used to assess the factors affecting its implementation and impact. RESULTS: Totally 80 students of the 2(nd) Professional MBBS were exposed to a competency-based education development project. It was found that the system was appreciated by faculty and students, especially the integration with clinical scenarios. There were many factors which influenced the execution of this program, including motivation level of students and faculty, time, logistics and meticulous planning. CONCLUSIONS: There was a significant improvement in student's performance and satisfaction. Many factors including prior planning were a major determinant for the success of this education development project. PMID- 26380217 TI - Assessment for learning with Objectively Structured Practical Examination in Biochemistry. AB - CONTEXT: Despite a radical shift in assessment methodologies over the last decade, the majority of medical colleges still follow the Traditional Practical Examination (TPE). TPE raises concerns about examiner variability, standardization, and uniformity of assessment. To address these issues and in line with the notion of assessments as motivating what and how students learn, Objectively Structured Practical Examination (OSPE) was introduced, as an assessment modality. Despite its usefulness, awareness and motivation to use the same, still needs to be probed. AIMS: To implement OSPE in the assessment of practical skills in biochemistry, and to know student and faculty perspectives regarding OSPE. SETTINGS AND DESIGN: OSPE was introduced at the stage of formative assessment of practical skills, for 94 year one MBBS students. SUBJECTS AND METHODS: Students were divided into two groups; the first group was evaluated by the traditional method and the second by OSPE. Students were crossed over on a second examination. The mean score obtained by both the methods was compared statistically. Students and faculty perspectives regarding OSPE were obtained by a questionnaire. Student performance was compared using "Bland-Altman technique," and Student's t-test. RESULTS: The mean scores of students was found to be significantly higher (P < 0.0001) when assessed with OSPE as compared to TPE. Number of students achieving >70% marks was also significantly higher with OSPE. Validity was supported by a significant correlation coefficient of comparison of marks by the two methods. Feedback from students and faculty indicated that they endorsed OSPE. CONCLUSIONS: This evaluation demonstrated the need for a structured approach to assessment. Going in line with the notion that assessment drives learning, introducing OSPE would help tailoring teaching-learning to optimize student satisfaction and learning. PMID- 26380218 TI - Blueprinting in assessment: A tool to increase the validity of undergraduate written examinations in pathology. AB - CONTEXT/BACKGROUND: Written examinations are the most commonly employed method for assessment of cognitive skills in medical education. The few disadvantages of essay questions are less number of questions, limited sampling, unfair distribution of questions over topics, vague questions etc., Blueprinting overcomes these issues, increasing the validity of examinations. OBJECTIVES: To describe the process of developing a blueprint for undergraduate written examinations in pathology; and to evaluate its effect as a tool to increase the content validity of assessment. METHODOLOGY: A workshop was conducted in the Department of Pathology to sensitize the faculty about the importance of blueprinting. A blueprint was prepared for written examinations in pathology, question papers were set accordingly and administered in preliminary examinations. Feedback was collected from the students and faculty to know their perceptions about the question papers with reference to blueprinting. RESULTS: The students and faculty felt that there was appropriate distribution of questions across topics (77% and 89%, respectively), appropriate weightage given to topics of public health importance (65% and 100%), examinations were fair (86% and 89%). All the faculty felt that blueprints aligns assessment with objectives and helps as a guide and to paper construction. CONCLUSIONS: Students were satisfied as blueprinting helped them to attempt examination better. The faculty who validated the blueprint felt that it helps in distribution of appropriate weightage and questions across the topics and blueprinting should be an integral part of assessment. PMID- 26380219 TI - The Non-Canonical Role of Aurora-A in DNA Replication. AB - Aurora-A is a well-known mitotic kinase that regulates mitotic entry, spindle formation, and chromosome maturation as a canonical role. During mitosis, Aurora A protein is stabilized by its phosphorylation at Ser51 via blocking anaphase promoting complex/cyclosome-mediated proteolysis. Importantly, overexpression and/or hyperactivation of Aurora-A is involved in tumorigenesis via aneuploidy and genomic instability. Recently, the novel function of Aurora-A for DNA replication has been revealed. In mammalian cells, DNA replication is strictly regulated for preventing over-replication. Pre-replication complex (pre-RC) formation is required for DNA replication as an initiation step occurring at the origin of replication. The timing of pre-RC formation depends on the protein level of geminin, which is controlled by the ubiquitin-proteasome pathway. Aurora A phosphorylates geminin to prevent its ubiquitin-mediated proteolysis at the mitotic phase to ensure proper pre-RC formation and ensuing DNA replication. In this review, we introduce the novel non-canonical role of Aurora-A in DNA replication. PMID- 26380220 TI - Scientific Rationale Supporting the Clinical Development Strategy for the Investigational Aurora A Kinase Inhibitor Alisertib in Cancer. AB - Alisertib (MLN8237) is a selective small molecule inhibitor of Aurora A kinase that is being developed in multiple cancer indications as a single agent and in combination with other therapies. A significant amount of research has elucidated a role for Aurora A in orchestrating numerous activities of cells transiting through mitosis and has begun to shed light on potential non-mitotic roles for Aurora A as well. These biological insights laid the foundation for multiple clinical trials evaluating the antitumor activity of alisertib in both solid cancers and heme-lymphatic malignancies. Several key facets of Aurora A biology as well as empirical data collected in experimental systems and early clinical trials have directed the development of alisertib toward certain cancer types, including neuroblastoma, small cell lung cancer, neuroendocrine prostate cancer, atypical teratoid/rhabdoid tumors, and breast cancer among others. In addition, these scientific insights provided the rationale for combining alisertib with other therapies, including microtubule perturbing agents, such as taxanes, EGFR inhibitors, hormonal therapies, platinums, and HDAC inhibitors among others. Here, we link the key aspects of the current clinical development of alisertib to the originating scientific rationale and provide an overview of the alisertib clinical experience to date. PMID- 26380221 TI - Disseminated Medulloblastoma in a Child with Germline BRCA2 6174delT Mutation and without Fanconi Anemia. AB - Medulloblastoma, the most common malignant brain tumor in children, occurs with increased frequency in individuals with Fanconi anemia who have biallelic germline mutations in BRCA2. We describe an 8-year-old child who had disseminated anaplastic medulloblastoma and a deleterious heterozygous BRCA2 6174delT germline mutation. Molecular profiling was consistent with Group 4 medulloblastoma. The posterior fossa mass was resected and the patient received intensive chemotherapy and craniospinal irradiation. Despite this, the patient succumbed to a second recurrence of his medulloblastoma, which presented 8 months after diagnosis as malignant pleural and peritoneal effusions. Continuous medulloblastoma cell lines were isolated from the original tumor (CHLA-01-MED) and the malignant pleural effusion (CHLA-01R-MED). Here, we provide their analyses, including in vitro and in vivo growth, drug sensitivity, comparative genomic hybridization, and next generation sequencing analysis. In addition to the BRCA2 6174delT, the medulloblastoma cells had amplification of MYC, deletion at Xp11.2, and isochromosome 17, but no structural variations or overexpression of GFI1 or GFI1B. To our knowledge, this is the first pair of diagnosis/recurrence medulloblastoma cell lines, the only medulloblastoma cell lines with BRCA2 6174delT described to date, and the first reported case of a child with medulloblastoma associated with a germline BRCA2 6174delT who did not also have Fanconi anemia. PMID- 26380222 TI - Breaching the Castle Walls: Hyaluronan Depletion as a Therapeutic Approach to Cancer Therapy. AB - Hyaluronan (HA) has many functions in the extracellular milieu of normal and diseased tissues. Disease-associated HA accumulation has been shown to predict a worsened prognosis in cancer patients, with tumors having a high-extracellular HA content (HA-high) being more aggressive than their HA-low counterparts. HA-high tumor aggressiveness is derived from the specialized biomechanical and molecular properties of the HA-based assembly of HA binding proteins and the growth promoting factors that accumulate in it. Biophysical characteristics of an HA high tumor microenvironment include high tumor interstitial pressure, compression of tumor vasculature, and resulting tumor hypoxia. Within the tumor cell membrane, HA receptors, primarily CD44 and RHAMM, anchor the HA-high extracellular network. HA-CD44 association on the tumor cell surface enhances receptor tyrosine kinase activity to drive tumor progression and treatment resistance. Together, malignant cells in this HA-high matrix may evolve dependency on it for growth. This yields the hypothesis that depleting HA in HA high tumors may be associated with a therapeutic benefit. A pegylated form of recombinant human hyaluronidase PH20 (PEGPH20) has been deployed as a potential cancer therapeutic in HA-high tumors. PEGPH20 can collapse this matrix by degrading the HA-assembled tumor extracellular framework, leading to tumor growth inhibition, preferentially in HA-high tumors. Enzymatic depletion of HA by PEGPH20 results in re-expansion of the tumor vasculature, reduction in tumor hypoxia, and increased penetration of therapeutic molecules into the tumor. Finally, HA-depletion results in reduced signaling via CD44/RHAMM. Taken together, HA-depletion strategies accomplish their antitumor effects by multiple mechanisms that include targeting both biophysical and molecular signaling pathways. Ongoing clinical trials are examining the potential of PEGPH20 in combination with partner therapeutics in several cancers. PMID- 26380224 TI - Sunitinib in Metastatic Renal Cell Carcinoma: A Systematic Review of UK Real World Data. AB - BACKGROUND: Real world data (RWD) are increasingly used to inform drug reimbursement decisions, but it is unclear how well outcomes from real world studies compare to those of clinical trials. This systematic review seeks to compare outcomes for sunitinib in routine UK clinical practice with the sunitinib registrational and expanded-access program clinical trials. METHOD: Systematic review of the real world published literature was undertaken. UK observational studies recording first- or second-line sunitinib efficacy were included. A qualitative summary of the results and comparison to the controlled clinical trials was conducted. Fifteen real world studies were included, 14 of which were only available as posters/presentations. RESULTS: Real world study reporting quality was generally low, making comparisons with the clinical trials difficult. Practice relating to starting dose, dose modification, timing of therapy initiation, and other factors varied between centers. Median progression-free survival and adverse events were generally comparable to the clinical trial outcomes, but overall survival was not. CONCLUSION: There are few published data on sunitinib use in UK clinical practice. Studies are characterized by lack of peer reviewed publication and heterogeneity in design, reporting, and analysis. For use of RWD in the reimbursement setting, data collection and reporting will need to improve. HIGHLIGHTS: There are few published data on sunitinib use in UK clinical practice. Studies are characterized by lack of peer reviewed publication and heterogeneity in design, reporting, and analysis. Practice varies considerably between different UK centers. Median progression-free survival and adverse events are generally comparable to the clinical trial outcomes, but overall survival is not. For use of real world data in the reimbursement setting, data collection and reporting will need to improve. PMID- 26380223 TI - Preclinical Childhood Sarcoma Models: Drug Efficacy Biomarker Identification and Validation. AB - Over the past 35 years, cure rates for pediatric cancers have increased dramatically. However, it is clear that further dose intensification using cytotoxic agents or radiation therapy is not possible without enhancing morbidity and long-term effects. Consequently, novel, less genotoxic, agents are being sought to complement existing treatments. Here, we discuss preclinical human tumor xenograft models of pediatric cancers that may be used practically to identify novel agents for soft tissue and bone sarcomas, and "omics" approaches to identifying biomarkers that may identify sensitive and resistant tumors to these agents. PMID- 26380225 TI - Nicotine: Carcinogenicity and Effects on Response to Cancer Treatment - A Review. AB - Tobacco use is considered the single most important man-made cause of cancer that can be avoided. The evidence that nicotine is involved in cancer development is reviewed and discussed in this paper. Both tobacco smoke and tobacco products for oral use contain a number of carcinogenic substances, such as polycyclic hydrocarbons and tobacco-specific N-nitrosamines (TSNA), which undoubtedly contribute to tobacco related cancer. Recent studies have shown that nicotine can affect several important steps in the development of cancer, and suggest that it may cause aggravation and recurrence of the disease. TSNA may be formed from nicotine in the body. The role of nicotine as the major addictive component of tobacco products may have distracted our attention from toxicological effects on cell growth, angiogenesis, and tumor malignancy. Effects on cancer disease are important aspects in the evaluation of possible long-term effects from sources of nicotine, such as e-cigarettes and products for nicotine replacement therapy, which both have a potential for life-long use. PMID- 26380226 TI - Evidence for genes associated with the ability of Mycobacterium avium subsp. hominissuis to escape apoptotic macrophages. AB - Mycobacterium avium subsp. hominissuis (MAH) is an environmental bacteria that infects immunocompromised humans. MAH cases are increasing in incidence, making it crucial to gain knowledge of the pathogenic mechanisms associated with the bacterium. MAH infects macrophages and after several days the infection triggers the phagocyte apoptosis. Many of the intracellular MAH escape the cell undergoing apoptosis leading to infection of neighboring macrophages. We screened a transposon bank of MAH mutants in U937 mononuclear phagocytes for the inability to escape macrophages undergoing apoptosis. Mutations in genes; MAV_2235, MAV_2120, MAV_2410, and MAV_4563 resulted in the inability of the bacteria to exit macrophages upon apoptosis. Complementation of the mutations corrected the phenotype either completely or partially. Testing for the ability of the mutants to survive in macrophages compared to the wild-type bacterium revealed that the mutant clones were not attenuated up to 4 days of infection. Testing in vivo, however, demonstrated that all the MAH clones were attenuated compared with the wild-type MAC 104 in tissues of mice. Although the mechanism associated with the bacterial inability to leave apoptotic macrophages is unknown, the identification of macrophage cytoplasm targets for the MAH proteins suggest that they interfere either with protein degradation machinery or post-translation mechanisms. The identification of tatC as a MAH protein involved in the ability of MAH to leave macrophages, suggests that secreted effector(s) are involved in the process. The study reveals a pathway of escape from macrophages, not shared with Mycobacterium tuberculosis. PMID- 26380227 TI - Direct association of visit-to-visit HbA1c variation with annual decline in estimated glomerular filtration rate in patients with type 2 diabetes. AB - BACKGROUND/AIMS: This study examined associations of visit-to-visit variability of glycemic control with annual decline in estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes attending an outpatient clinic. METHODS: Intrapersonal mean and coefficient of variation (CV) of 8-12 measurements of HbA1c and those of 4-6 measurements of fasting and post-breakfast plasma glucose (FPG and PPG, respectively) during the first 12 months after enrollment were calculated in a cohort of 168 patients with type 2 diabetes. Annual changes in eGFR were computed using 52 (median) creatinine measurements obtained over a median follow-up of 6.0 years. Multivariate linear regressions assessed the independent correlates of changes in eGFR. RESULTS: CV-HbA1c (standardized beta, 0.257,p = 0.004) were significantly and log urine albumin/creatinine ratio (standardized beta,-0.155,p = 0.085) and smoking (standardized beta,-0.186,p = 0.062) tended to be associated with annual eGFR decline independently of mean HbA1c, age, sex, BMI, waist circumference, diabetes duration and therapy, means and CVs of FPG, PPG and systolic blood pressure, baseline eGFR, and uses of anti hypertensive and lipid-lowering medications. Association between HbA1c variability and renal function decline was stronger in patients with albumin/creatinine ratio ? 30 mg/g than in those with normoalbuminuria (r = 0.400, p = 0.003 and r = -0.169, p = 0.07, respectively). CONCLUSIONS: Consistency of glycemic control is important to preserve kidney function in type 2 diabetic patients, in particular, in those with nephropathy. PMID- 26380228 TI - Association between serum uric acid level and metabolic syndrome components. AB - BACKGROUND: Serum uric acid levels is reported to be associated with a variety of cardiometabolic risk factors; however, its direct association with metabolic syndrome (MetS) remains controversial. Thus, we examined the association of serum uric acid concentrations with the MetS components. METHODS: MetS was defined according to the National Cholesterol Education Program (NCEP) criteria. This case-control study comprised 101 non-smoking individuals (41 in the MetS group and 60 in the non-MetS group). Blood pressure, fasting plasma glucose, insulin, HOMA-IR, lipid profiles, uric acid, and anthropometric measures were determined, and body composition was assessed by using bioelectrical impedance analysis (BIA). RESULTS: After adjustment for confounding factors, serum uric acid was significantly higher in MetS group than non-MetS group (5.70 +/- 1.62 vs 4.97 +/- 1.30 mg/dL, respectively, P = 0.001). After controlling for age, sex and body mass index in partial correlation analysis, uric acid was positively correlated with triglycerides, and negatively with HDL-C. In multiple logistic regression analysis, every 1 mg/dl elevation in the serum uric acid level increased the risk of MetS approximately by 2-folds (OR: 2.11, 95 % CI: 1.30-3.41). CONCLUSION: This study showed that those individuals with MetS have higher uric acid levels; the association of uric acid and MetS components supports that it might be an additional components of MetS. PMID- 26380229 TI - Semi-rigid penile prosthesis as a salvage management of idiopathic ischemic stuttering priapism. AB - INTRODUCTION: Priapism is the persistent erection resulting from dysfunction of the mechanisms that regulate penile swelling, stiffness, and sagging. It is a full or partial erection that persists for a period more than 4 hours beyond sexual stimulation and/or orgasm or is unrelated to sexual stimulation. Ischemic priapism should be managed in a step-by-step fashion. OBJECTIVE: To demonstrate step-by-step management of stuttering refractory ischemic priapism. We report a case of stuttering refractory ischemic priapism. Moreover, we reviewed different approaches to priapism management in the literature. CASE PRESENTATION: A 53-year old male presented with a painful erection of 29 hours' duration, probably caused by consumption of alcohol. The penile blood gas showed a pH of 7.08, PCO2 of 75 mmHg and PO2 of 39 mmHg. Aspiration was followed by irrigation of an alpha adrenergic, Winter and T-shunt operations were preformed, and finally a semi rigid penile prosthesis was implanted to overcome the refractory stuttering ischemic priapism. CONCLUSION: In case of stuttering refractory ischemic priapism, immediate implantation of a penile prosthesis is a simple and effective procedure that manages both the acute episode and the inevitable erectile dysfunction that would otherwise occur, while preserving penile length. PMID- 26380230 TI - Optimal management of muscle-invasive bladder cancer - a review. AB - Muscle-invasive bladder cancer is a complex disease requiring aggressive management. Patients are often older with comorbid conditions that impact treatment options. This review describes the available therapies for invasive urothelial carcinoma, including chemotherapy, radical extirpative surgery, and bladder-preserving strategies. PMID- 26380231 TI - DESIGNING DRUG TRIALS FOR SARCOPENIA IN OLDER ADULTS WITH HIP FRACTURE - A TASK FORCE FROM THE INTERNATIONAL CONFERENCE ONFRAILTY AND SARCOPENIA RESEARCH (ICFSR). AB - In May 2012, a Sarcopenia Consensus Summit was convened by the Foundation of the National Institutes of Health (FNIH), National Institute of Aging (NIA), and the U.S. Food and Drug Administration (FDA); and co-sponsored by five pharmaceutical companies. At this summit, sarcopenia experts from around the world worked to develop agreement on a working definition of sarcopenia, building on the work of previous efforts to generate a consensus. With the ultimate goal of improving function and independence in individuals with sarcopenia, the Task Force focused its attention on people at greatly increased risk of muscle atrophy as a consequence of hip fracture. The rationale for looking at this population is that since hip fracture is a recognized condition, there is a clear regulatory path forward for developing interventions. Moreover, patients with hip fracture may provide an appropriate population to advance understanding of sarcopenia, for example helping to define diagnostic criteria, develop biomarkers, understand the mechanisms that underlie the age-related loss of muscle mass and strength, and identify endpoints for clinical trials that are reliable, objective, and clinically meaningful. Task Force members agreed that progress in treating sarcopenia will require strengthening of partnerships between academia, industry, and government agencies, and across continents to reach consensus on diagnostic criteria, optimization of clinical trials design, and identification of improved treatment and preventive strategies. In this report, the main results of the Task Force discussion are presented. PMID- 26380233 TI - Cigarette smoking effect on human cochlea responses. AB - BACKGROUND: Smoking is one of the most important risk factor in increasing of non communicable disorders, especially chronic diseases such as cancer, stroke, heart and respiratory diseases. Cigarette smoking could damage the cochlea and causing hearing loss. The otoacoustic emission (OAE) is a source of information for determining cochlear responses to sound stimuli and how to change the response of the auditory system in some diseases. OAE test was sensitive to outer hair cells (OHCs) activity. MATERIALS AND METHODS: In this study, tried to evaluate a hearing threshold of the smoker group versus non-smoker ones through pure tone audiometery, transient evoked otoacoustic emission (TEOAE) and distortion product otoacoustic emission (DPOAE) tests. RESULTS: The results indicated that significant decrement of 8000 Hz threshold, reduced DPOAE/TEOAE amplitude in the smoker group than non-smoker one (P < 0.05). DPOAE amplitudes decline reflects the cochlear damage caused by smoking. CONCLUSION: OAEs test was clinically non invasive, accurate, and objective evaluation of the performance of cochlear OHCs. PMID- 26380232 TI - Bridging the Translation Gap: From Dementia Risk Assessment to Advice on Risk Reduction. AB - Dementia risk reduction is a global health and fiscal priority given the current lack of effective treatments and the projected increased number of dementia cases due to population ageing. There are often gaps among academic research, clinical practice, and public policy. We present information on the evidence for dementia risk reduction and evaluate the progress required to formulate this evidence into clinical practice guidelines. This narrative review provides capsule summaries of current evidence for 25 risk and protective factors associated with AD and dementia according to domains including biomarkers, demographic, lifestyle, medical, and environment. We identify the factors for which evidence is strong and thereby especially useful for risk assessment with the goal of personalising recommendations for risk reduction. We also note gaps in knowledge, and discuss how the field may progress towards clinical practice guidelines for dementia risk reduction. PMID- 26380234 TI - Isolation, cloning, and expression of E. coli BirA gene for biotinylation applications. AB - BACKGROUND: The key enzyme in biotin-(strept) avidin systems, Escherichia coli BirA biotin ligase, is currently obtained by overexpression of the long protein tagged versions of the gene to prevent its toxic effect in E. coli. Herein we describe a rather simple and efficient system for expression of E. coli BirA without the application of long-tag proteins. MATERIALS AND METHODS: The coding sequence of BirA gene was isolated by polymerase chain reaction using DNA extract of E. coli-DH5alpha as template. BirA amplicon harboring a GS-linker at its C terminal was cloned into NdeI-XhoI sites of pET24a(+) vector under control of T7 promoter and upstream of the vector-derived 6xHis-tag. pET24-BirA transformed BL21-cells were induced for protein expression by IPTG and analyzed by SDS-PAGE and Western blotting. Protein expression yields were assessed by image analysis of the SDS-PAGE scans using ImageJ software. RESULT: Agarose gel electrophoresis indicated proper size of the BirA gene amplicon (963 bp) and accuracy of the recombinant pET24-BirA construct. Sequence alignment analysis indicated identical sequence (100%) of our isolate with that of the standard E. coli-K12 BirA gene sequence (accession number: NC_000913.3). SDS-PAGE and Western blot results indicated specific expression of the 36.6 kDa protein corresponding to the BirA protein. Image analysis estimated a yield of 12% of total protein for the BirA expression. CONCLUSIONS: By application of pET24a(+) we achieved relatively high expression of BirA in E. coli without application of any long protein-tags. Introduction of the present expression system may provide more readily available source of BirA enzyme for (strept) avidin-biotin applications and studies. PMID- 26380235 TI - Effects of repeated treatment with cholecystokinin sulfated octapeptide on passive avoidance memory under chronic restraint stress in male rats. AB - BACKGROUND: Cholecystokinin (CCK), a peptide hormone found in the gut is the most abundant peptide neurotransmitter in the brain as well, and its effects on learning, memory, and anxiety have been shown. However, it is not clear whether this substance acts as a mediator for anxiety and stress induction or inhibits them. Hence, the purpose of this study was to evaluate the effects of CCK on memory function under stress conditions. MATERIALS AND METHODS: Male Wistar rats were divided into four groups: The control, the control-CCK, the stress, and stress-CCK. To induce stress, the rats were placed within adjustable restraint chambers for 6 h daily, for 24 days. CCK-8S (cholecystokinin sulfated octapeptide was injected before induction of stress (1.6 MUg/kg, intraperitoneal) for 24 days. Passive avoidance learning test was used for evaluation of learning and memory. Rats received foot electrical shock before stress induction and CCK injection and step through latencies were evaluated 1-day after the last session of stress and treatments. RESULTS: Stress impaired memory significantly (P < 0.05). Although CCK per se decreased memory (P < 0.05), it prevented the memory impairments in the stress group as there was no significant difference between the control and stress-CCK groups. CONCLUSION: Stress has a profound effect on cognition and CCK probably acts as a mediator for its action. Our results showed that a high concentration of CCK during stress may be helpful in alleviating the effects of stress on the brain. PMID- 26380236 TI - Evaluation of the circulating CD34(+), CD309(+), and endothelial progenitor cells in patients with first attack of optic neuritis. AB - BACKGROUND: Endothelial progenitor cells (EPCs) are present in circulation and contribute to vasculogenesis in adults. The aim of the present study was to determine the number of circulating EPCs in patients with optic neuritis (ON). MATERIALS AND METHODS: Fifty patients with ON were diagnosed by expert neurologist and optometrist at the Feiz Hospital, Isfahan, Iran (2012-2013). Blood samples were collected from ON patients in the first attack. The number of EPCs was measured by flow cytometry through the assessment of CD34(+) and CD309(+) in patients and healthy individuals. RESULTS: With using flow cytometry, CD34(+) and CD309(+) cells detected in peripheral blood cells of patients (n = 50) with ON, and healthy individuals (n = 30). Patients with ON had (mean = 66.71 +/- 17.82) CD34(+) and CD309(+) cells compared with healthy controls (mean = 28.72 +/- 22.46). In addition, there was no significant difference in CD309(+) cells in both groups. CONCLUSION: This study showed elevated CD34(+) and CD309(+) cells in the early stage of the disease. Regarded to EPC increment in neural repair, it expected the EPC level be increased in these patients, but no detectable differences were observed among both markers in healthy and patient with first attack. PMID- 26380237 TI - Molecular typing of Iranian mycobacteria isolates by polymerase chain reaction restriction fragment length polymorphism analysis of 360-bp rpoB gene. AB - BACKGROUND: Diagnosis and typing of Mycobacterium genus provides basic tools for investigating the epidemiology and pathogenesis of this group of bacteria. Polymerase chain reaction (PCR)-restriction fragment length polymorphism analysis (PRA) is an accurate method providing diagnosis and typing of species of mycobacteria. The present study is conducted by the purpose of determining restriction fragment profiles of common types of mycobacteria by PRA method of rpoB gene in this geographical region. MATERIALS AND METHODS: Totally 60 clinical and environmental isolates from February to October, 2013 were collected and subcultured and identified by phenotypic methods. A 360 bp fragment of the rpoB gene amplified by PCR and products were digested by MspI and HaeIII enzymes. RESULTS: In the present study, of all mycobacteria isolates identified by PRA method, 13 isolates (21.66%) were Mycobacterium tuberculosis, 34 isolates (56.66%) were rapidly growing Nontuberculosis Mycobacteria (NTM) that including 26 clinical isolates (43.33%) and 8 environmental isolates (13.33%), 11 isolates (18.33%) were clinical slowly growing NTM. among the clinical NTM isolates, Mycobacterium fortuitum Type I with the frequency of 57.77% was the most prevalent type isolates. Furthermore, an unrecorded of the PRA pattern of Mycobacterium conceptionense (HeaIII: 120/90/80, MspI: 120/105/80) was found. This study demonstrated that the PRA method was high discriminatory power for identification and typing of mycobacteria species and was able to identify 96.6% of all isolates. CONCLUSION: Based on the result of this study, rpoB gene could be a potentially useful tool for identification and investigation of molecular epidemiology of mycobacterial species. PMID- 26380238 TI - The effect of preemptive pudendal nerve block on pain after anterior and posterior vaginal repair. AB - INTRODUCTION: Anterior and posterior vaginal repair (APR) is a common surgery for women with prolapse of pelvic organs which creates post-operative pain because of damage of tissues that we should manage and control this pain. For this purpose, this study was conducted in order to evaluate the effect of preemptive pudendal nerve block on post-operative pain in anterior and posterior vaginal wall repair. MATERIALS AND METHODS: In a double-blinded clinical trial study, 60 women candidates of APR were randomly divided to two groups. In both of them was injected 0.3 cc/kg bupivacaine 0.25% for the intervention group or normal saline for the control group in pudendal nerve tract with the guide of nerve stimulator. A visual analog scale was used to measure pain during the first 48 h after the surgery. Data were analyzed by repeated measures analysis of variance (ANOVA). RESULTS: Compared with the intervention group, the control group experienced greater pain during rest and walking. There were significant differences between the two groups from the first post-operative hour (P = 0.003) until 48 h after the operation (P = 0.021). Furthermore, the mean +/- SD values of pain in the sitting position was not significantly different between control and intervention groups at the same time (P = 0.340). CONCLUSION: Preemptive pudendal nerve block can reduce post-operative pain score in anterior and posterior vaginal wall repair and this method was suggested in anterior and posterior vaginal wall repair. PMID- 26380239 TI - Immunohistochemical (Ki-67) study of endometrial maturation in mice after use of phosphodiesterase type 5 inhibitor. AB - BACKGROUND: Uterine receptivity for the implantation is a complicated process, that ovarian factors (hormonal), endometrium and embryo simultaneously are involved in this phenomenon. A successful implantation needs appropriate development of the endometrium. Furthermore, embryo must be capable of reacting with the endometrium and producing suitable adhesion molecules. This study aimed to examine one of endometrial maturation indices in mice before implantation, i.e., proliferation of stromal cells. MATERIALS AND METHODS: A total of 40 adult female mice were divided into four groups: Control, gonadotropin, gonadotropin + progesterone, and gonadotropin + sildenafil citrate. The three experimental groups were first injected 7.5 IU of human chorionic gonadotropin (HCG) and then 7.5 IU of human menopausal gonadotropin (HMG). Then, every two female mice were placed in a cage with a male mouse for mating. Two groups were injected 1 mg of progesterone and 3 mg/kg of sildenafil citrate at intervals of 24, 48, and 72 h after injection of HMG. After 96 h, all the mice were killed, and their uterine samples subjected to tissue passage and prepared for analysis. Immunohistochemical method, Ki-67, and stromal mitotic cell count were used in this study. RESULTS: Our observations in all groups showed changes in the luminal epithelium. ANOVA analysis Ki-67-positive stromal cells among all groups were not statistically significant. CONCLUSION: The results showed that administration of HMG and HCG following that of progesterone and sildenafil citrate could change the indices of endometrial maturation, and they were not involved in the phase immediately before implantation in stromal mitotic index. PMID- 26380240 TI - Survey of the detoxification effect of green tea extract on the reproductive system in rats exposed to lead acetate. AB - BACKGROUND: Lead poisoning has been an old but perpetual public health problem in developing countries. Lead has an adverse effect on fertility, and this study aimed to examine the effect of consuming green tea extract (GTE) on fertility parameters in rats exposed to lead. MATERIALS AND METHODS: In this experimental study, 70 rats have been classified, as it is described later, into 4 groups of 10 and were studied over 2 months. Group 1: Normal diet and tap water; Group 2: 10 mg/kg intraperitoneal lead acetate weekly over 8 weeks; Group 3: Lead acetate + 100 mg/kg green tea, Group 4: Extract green tea. Distal epididymal sperm samples were collected to assess the sperm counts, motility, and morphology. Testicular tissue and blood level of testosterone were also studies. Data were analyzed by SPSS-17 software using ANOVA and independent t-test with a significant level of 0.05. RESULTS: The rats exposed to lead acetate had the lowest weight, and green tea had the highest weight. Green tea consumption in rats exposed to lead, reduced the effect of lead and the difference in mean body weight in these rats, compared to other groups, was minimized (P < 0.05). The group exposed to lead acetate had the highest sperm abnormalities, and the lowest sperm abnormalities were observed in groups taking green tea. CONCLUSION: Consumption of green tea can reduce the adverse effects of lead, and also can effectively prevent fertility reduction. PMID- 26380241 TI - Genetic characterization of Pseudomonas aeruginosa-resistant isolates at the university teaching hospital in Iran. AB - BACKGROUND: Pseudomonas aeruginosa is an opportunistic pathogen that is commonly responsible for nosocomial infections. The aim of this study was to perform a genotyping analysis of the Pseudomonas aeruginosa-resistant isolates by the multilocus sequence typing (MLST) method at the university teaching hospital in Iran. MATERIALS AND METHODS: Antimicrobial susceptibility was analyzed for P. aeruginosa isolates. Ceftazidime-resistant (CAZres) isolates with a positive double-disc synergy test were screened for the presence of extended-spectrum beta lactamase-encoding genes. Phenotypic tests to detect the metallo-beta-lactamase strains of P. aeruginosa were performed on imipenem-resistant (IMPres) isolates. Selected strains were characterized by MLST. RESULTS: Of 35 P. aeruginosa isolates, 71%, 45% and 45% of isolates were CAZres, IMPres and multidrug resistant (MDR), respectively. Fifty-seven percent of the isolates carried the bla OXAgroup-1. All the five typed isolates were ST235. Isolates of ST235 that were MDR showed a unique resistance pattern. CONCLUSION: This study shows a high rate of MDR P. aeruginosa isolates at the university teaching hospital in Iran. It seems MDR isolates of P. aeruginosa ST235 with unique resistance pattern disseminated in this hospital. PMID- 26380242 TI - Music therapy: An effective approach in improving social skills of children with autism. AB - BACKGROUND: The existing methodological weakness in conducted researches concerning music therapy (MT) for children with autism led to ambiguity and confusion in this scope of studies. The aim of the present research is to identify the effectiveness of MT method in improving social skills of children with autism and its stability, as well. MATERIALS AND METHODS: In the form of a clinical trial study with design of pretest/posttest/follow-up with control group, among the children with autism in community of Tehran city, on the basis of childhood autism rating scale, 27 children with mild to moderate autism were chosen and were divided into two groups of experiment (n = 13), and control (n = 14). Social skills' level of both groups was measured and recorded with the help of social skills rating system scale. The children of the experiment group participated in MT programs of Orff-Schulwerk for 45 days in 12 sessions (two sessions of 1-h/week), whereas the control group received no intervention. The data were analyzed with Statistic Package For Social Science (SPSS) software t test and analysis of covariance was used to compare groups. RESULTS: In posttest, the results of covariance analysis showed a significant increase in social skills' scores of the experiment group (P < 0.001). Also, results of the paired sample t-test showed that the effectiveness of MT has been persistent up to the follow-up phase. CONCLUSIONS: The study showed that MT is an effective method with deep and consistent effects on improving social skills of children with autism. PMID- 26380243 TI - Effect of Gamma-aminobutyric acid on kidney injury induced by renal ischemia reperfusion in male and female rats: Gender-related difference. AB - BACKGROUND: The most important cause of kidney injury is renal ischemia/reperfusion injury (IRI), which is gender-related. This study was designed to investigate the protective role of Gamma-aminobutyric acid (GABA (against IRI in male and female rats. MATERIALS AND METHODS: Thirty-six female and male wistar rats were assigned to six experimental groups. The IRI was induced by clamping renal vessels for 45 min then was performed reperfusion for 24 h. The group sex posed to IRI were pretreated with GABA and were compared with the control groups. RESULTS: Serum levels of creatinine and blood urea nitrogen, kidney weight, and kidney tissue damage score increased in the IRI alone groups, (P < 0.05), while GABA decreased these parameters in female significantly (P < 0.05), but not in male rats. Uterus weight decreased significantly in female rats treated with GABA. Testis weight did not alter in male rats. Serum level of nitrite and kidney level of malondialdehyde (MDA) had no significant change in both female and male rats. Kidney level of nitrite increased significantly in female rats experienced IRI and serum level of MDA increased significantly in males that were exposed to IRI (P < 0.05). CONCLUSION: GABA could ameliorate kidney injury induced by renal IRI in a gender dependent manner. PMID- 26380244 TI - Partial purification and biochemical characterization of peroxidase from rosemary (Rosmarinus officinalis L.) leaves. AB - BACKGROUND: In this study, it is aimed to purify POD from leaves of Rosmarinus officinalis L. and determine its some biochemical properties. PODs are a group of oxidoreductase enzymes that catalyze the oxidation of a wide variety of phenolic compounds in the presence of hydrogen peroxide as an electron acceptor. MATERIALS AND METHODS: In this investigation, POD was purified 9.3-fold with a yield of 32.1% from the leaves of Rosemary by ammonium sulfate precipitation and ion exchange chromatography. The enzyme biochemical properties, including the effect of pH, temperature and ionic strength were investigated with guaiacol as an electron donor. For substrate specificity investigation of the enzyme, Michaelis constant and the maximum velocity of an enzymatic reaction values for substrates guaiacol and 3,3', 5,5'-TetraMethyle-Benzidine were calculated from the Lineweaver-Burk graphs. RESULTS: The POD optimum pH and temperature were 6.0 and 40 degrees C. The POD activity was maximal at 0.3 M of sodium phosphate buffer concentration (pH 6.0). Sodium dodecyl sulphate polyacrylamide gel electrophoresis was performed for molecular weight (Mw) determination and Mw of the enzyme was found to be 33 kDa. To investigate the homogeneity of the POD, native-PAGE was done and a single band was observed. CONCLUSION: The stability against high temperature and extreme pH demonstrated that the enzyme could be a potential POD source for various applications in the medicine, chemical and food industries. PMID- 26380246 TI - Erythropoietin Attenuates Pulmonary Vascular Remodeling in Experimental Pulmonary Arterial Hypertension through Interplay between Endothelial Progenitor Cells and Heme Oxygenase. AB - BACKGROUND: Pulmonary arterial hypertension (PAH) is a pulmonary vascular disease with a high mortality, characterized by typical angio-proliferative lesions. Erythropoietin (EPO) attenuates pulmonary vascular remodeling in PAH. We postulated that EPO acts through mobilization of endothelial progenitor cells (EPCs) and activation of the cytoprotective enzyme heme oxygenase-1 (HO-1). METHODS: Rats with flow-associated PAH, resembling pediatric PAH, were treated with HO-1 inducer EPO in the presence or absence of the selective HO-activity inhibitor tin-mesoporphyrin (SnMP). HO activity, circulating EPCs and pulmonary vascular lesions were assessed after 3 weeks. RESULTS: In PAH rats, circulating EPCs were decreased and HO activity was increased compared to control. EPO treatment restored circulating EPCs and improved pulmonary vascular remodeling, as shown by a reduced wall thickness and occlusion rate of the intra-acinar vessels. Inhibition of HO activity with SnMP aggravated PAH. Moreover, SnMP treatment abrogated EPO-induced amelioration of pulmonary vascular remodeling, while surprisingly further increasing circulating EPCs as compared with EPO alone. CONCLUSION: In experimental PAH, EPO treatment restored the number of circulating EPCs to control level, improved pulmonary vascular remodeling, and showed important interplay with HO activity. Inhibition of increased HO activity in PAH rats exacerbated progression of pulmonary vascular remodeling, despite the presence of restored number of circulating EPCs. We suggest that both EPO-induced HO-1 and EPCs are promising targets to ameliorate the pulmonary vasculature in PAH. PMID- 26380247 TI - Investigation on the Factors Affecting Cronobacter sakazakii Contamination Levels in Reconstituted Powdered Infant Formula. AB - INTRODUCTION: Certain strains of Cronobacter sakazakii can cause serious invasive infections in children, mainly those <2 months old and fed with powdered infant formula (PIF). The infectious dose of C. sakazakii is unknown but evidence suggests that it is approximately 1000 colony forming units (CFU). PIF is currently considered safe if its end-product C. sakazakii level is <1 CFU/g. In this study, we determined the lag time, generation time (GT), and growth rate of five pooled C. sakazakii isolates to evaluate the factors affecting contamination levels in reconstituted PIF. METHODS: 1.71 log CFU/ml of C. sakazakii were inoculated into 100 and 3000 ml of reconstituted PIF and incubated at 22 and 35 degrees C. Growth was evaluated over a 24-h period. ComBase was used for modeling. RESULTS: In 3000 ml, the growth rate was 0.45 +/- 0.02 log CFU/h with a lag phase of 3 +/- 0.05 h and GT of 0.67 h at 22 degrees C, while the growth rate was 0.73 +/- 0.01 log CFU/h with a lag phase of 0.45 +/- 0.03 h and GT of 0.41 h at 35 degrees C. CONCLUSION: Cronobacter sakazakii grows rapidly in reconstituted PIF, especially at 35 degrees C. PMID- 26380245 TI - MicroRNAs and Potential Targets in Osteosarcoma: Review. AB - Osteosarcoma is the most common bone cancer in children and young adults. Surgery and multi-agent chemotherapy are the standard treatment regimens for this disease. New therapies are being investigated to improve overall survival in patients. Molecular targets that actively modulate cell processes, such as cell cycle control, cell proliferation, metabolism, and apoptosis, have been studied, but it remains a challenge to develop novel, effective-targeted therapies to treat this heterogeneous and complex disease. MicroRNAs (miRNAs) are small non coding RNAs that play critical roles in regulating cell processes including growth, development, and disease. miRNAs function as oncogenes or tumor suppressors to regulate gene and protein expression. Several studies have demonstrated the involvement of miRNAs in the pathogenesis of osteosarcoma with the potential for development in disease diagnostics and therapeutics. In this review, we discuss the current knowledge on the role of miRNAs and their target genes and evaluate their potential use as therapeutic agents in osteosarcoma. We also summarize the efficacy of inhibition of oncogenic miRNAs or expression of tumor suppressor miRNAs in preclinical models of osteosarcoma. Recent progress on systemic delivery as well as current applications for miRNAs as therapeutic agents has seen the advancement of miR-34a in clinical trials for adult patients with non-resectable primary liver cancer or metastatic cancer with liver involvement. We suggest a global approach to the understanding of the pathogenesis of osteosarcoma may identify candidate miRNAs as promising biomarkers for this rare disease. PMID- 26380248 TI - Capturing Public Opinion on Public Health Topics: A Comparison of Experiences from a Systematic Review, Focus Group Study, and Analysis of Online, User Generated Content. AB - BACKGROUND: Capturing public opinion toward public health topics is important to ensure that services, policy, and research are aligned with the beliefs and priorities of the general public. A number of approaches can be used to capture public opinion. METHODS: We are conducting a program of work on the effectiveness and acceptability of health promoting financial incentive interventions. We have captured public opinion on financial incentive interventions using three methods: a systematic review, focus group study, and analysis of online user-generated comments to news media reports. In this short editorial-style piece, we compare and contrast our experiences with these three methods. RESULTS: Each of these methods had their advantages and disadvantages. Advantages include tailoring of the research question for systematic reviews, probing of answers during focus groups, and the ability to aggregate a large data set using online user-generated content. However, disadvantages include needing to update systematic reviews, participants conforming to a dominant perspective in focus groups, and being unable to collect respondent characteristics during analysis of user-generated online content. That said, analysis of user-generated online content offers additional time and resource advantages, and we found it elicited similar findings to those obtained via more traditional methods, such as systematic reviews and focus groups. CONCLUSION: A number of methods for capturing public opinions on public health topics are available. Public health researchers, policy makers, and practitioners should choose methods appropriate to their aims. Analysis of user-generated online content, especially in the context of news media reports, may be a quicker and cheaper alternative to more traditional methods, without compromising on the breadth of opinions captured. PMID- 26380249 TI - Estimating the Fiscal Effects of Public Pharmaceutical Expenditure Reduction in Greece. AB - The purpose of the present study is to estimate the impact of pharmaceutical spending reduction on public revenue, based on data from the national health accounts as well as on reports of Greece's organizations. The methodology of the analysis is structured in two basic parts. The first part presents the urgency for rapid cutbacks on public pharmaceutical costs due to the financial crisis and provides a conceptual framework for the contribution of the Greek pharmaceutical branch to the country's economy. In the second part, we perform a quantitative analysis for the estimation of multiplier effects of public pharmaceutical expenditure reduction on main revenue sources, such as taxes and social contributions. We also fit projection models with multipliers as regressands for the evaluation of the efficiency of the particular fiscal measure in the short run. According to the results, nearly half of the gains from the measure's application is offset by financially equivalent decreases in the government's revenue, i.e., losses in tax revenues and social security contributions alone, not considering any other direct or indirect costs. The findings of multipliers' high value and increasing short-term trend imply the measure's inefficiency henceforward and signal the risk of vicious circles that will provoke the economy's deprivation of useful resources. PMID- 26380250 TI - Adding Dimensions to the Analysis of the Quality of Health Information of Websites Returned by Google: Cluster Analysis Identifies Patterns of Websites According to their Classification and the Type of Intervention Described. AB - BACKGROUND AND AIMS: Most of the instruments used to assess the quality of health information on the Web (e.g., the JAMA criteria) only analyze one dimension of information quality (IQ), trustworthiness. In this study, we analyzed the type of intervention that websites describe, whether supported by evidence-based medicine (EBM) or not, to provide a further dimension of IQ, accuracy, and correlated this with the established criteria. METHODS: We searched Google for "migraine cure" and analyzed the first 200 websites for: (1) JAMA criteria (authorship, attribution, disclosure, currency); (2) class of websites (commercial, health portals, professional, patient groups, no-profit); and (3) type of intervention described (approved drugs, alternative medicine, food, procedures, lifestyle, drugs still at the research stage). We used hierarchical cluster analysis to identify different patterns of websites according to their classification and the information provided. Subgroup analysis on the first 10 websites returned was performed. RESULTS: Google returned health portals (44%), followed by commercial websites (31%) and journalism websites (11%). The type of intervention mentioned most often was alternative medicine (55%), followed by procedures (49%), lifestyle (42%), food (41%), and approved drugs (35%). Cluster analysis indicated that health portals are more likely to describe more than one type of treatment while commercial websites most often describe only one. The average JAMA score of commercial websites was significantly lower than for health portals or journalism websites, and this was mainly due to lack of information on the authors of the text and indication of the date the information was written. Looking at the first 10 websites from Google, commercial websites are underrepresented and approved drugs overrepresented. CONCLUSION: Analyzing the type of therapies/prevention methods provides additional information to the trustworthiness measures, such as the JAMA score, and could be a convenient and objective indicator of websites whose information is based on EBM. PMID- 26380251 TI - Improvements in Neonatal and Childhood Medical Care - Perspective from the Balkans. PMID- 26380252 TI - Paying Out-of-Pocket and Informally for Health Care in Albania: The Impoverishing Effect on Households. PMID- 26380253 TI - Editorial: Health Education - Fostering Public Health Literacy through Innovative Educational Activities and Resources. PMID- 26380254 TI - Editorial: Radiation-induced and oxidative DNA damages. PMID- 26380255 TI - An epidemiological analysis of potential associations between C-reactive protein, inflammation, and prostate cancer in the male US population using the 2009-2010 National Health and Nutrition Examination Survey (NHANES) data. AB - Prostate cancer is the second leading cause of cancer-related deaths in US males, yet much remains to be learned about the role of inflammation in its etiology. We hypothesized that preexisting exposure to chronic inflammatory conditions caused by infectious agents or inflammatory diseases increase the risk of prostate cancer. Using the 2009-2010 National Health and Nutrition Examination Survey, we examined the relationships between demographic variables, inflammation, infection, circulating plasma C-reactive protein (CRP), and the risk of occurrence of prostate cancer in US men over 18 years of age. Using IBM SPSS, we performed bivariate and logistic regression analyses using high CRP values as the dependent variable and five study covariates including prostate cancer status. From 2009-2010, an estimated 5,448,373 men reported having prostate cancer of which the majority were Caucasian (70.1%) and were aged 40 years and older (62.7%). Bivariate analyses demonstrated that high CRP was not associated with an increased risk of prostate cancer. Greater odds of having prostate cancer were revealed for men that had inflammation related to disease (OR = 1.029, CI 1.029 1.029) and those who were not taking drugs to control inflammation (OR = 1.330, CI 1.324-1.336). Men who did not have inflammation resulting from non-infectious diseases had greater odds of not having prostate cancer (OR = 1.031, CI 1.030 1.031). Logistic regression analysis yielded that men with the highest CRP values had greater odds of having higher household incomes and lower odds of having received higher education, being aged 40 years or older, being of a race or ethnicity different from other, and of having prostate cancer. Our results show that chronic inflammation of multiple etiologies is a risk factor for prostate cancer and that CRP is not associated with this increased risk. Further research is needed to elucidate the complex interactions between inflammation and prostate cancer. PMID- 26380256 TI - Comparison of Standard and Novel Signal Analysis Approaches to Obstructive Sleep Apnea Classification. AB - Obstructive sleep apnea (OSA) is a disorder characterized by repeated pauses in breathing during sleep, which leads to deoxygenation and voiced chokes at the end of each episode. OSA is associated by daytime sleepiness and an increased risk of serious conditions such as cardiovascular disease, diabetes, and stroke. Between 2 and 7% of the adult population globally has OSA, but it is estimated that up to 90% of those are undiagnosed and untreated. Diagnosis of OSA requires expensive and cumbersome screening. Audio offers a potential non-contact alternative, particularly with the ubiquity of excellent signal processing on every phone. Previous studies have focused on the classification of snoring and apneic chokes. However, such approaches require accurate identification of events. This leads to limited accuracy and small study populations. In this work, we propose an alternative approach which uses multiscale entropy (MSE) coefficients presented to a classifier to identify disorder in vocal patterns indicative of sleep apnea. A database of 858 patients was used, the largest reported in this domain. Apneic choke, snore, and noise events encoded with speech analysis features were input into a linear classifier. Coefficients of MSE derived from the first 4 h of each recording were used to train and test a random forest to classify patients as apneic or not. Standard speech analysis approaches for event classification achieved an out-of-sample accuracy (Ac) of 76.9% with a sensitivity (Se) of 29.2% and a specificity (Sp) of 88.7% but high variance. For OSA severity classification, MSE provided an out-of-sample Ac of 79.9%, Se of 66.0%, and Sp = 88.8%. Including demographic information improved the MSE-based classification performance to Ac = 80.5%, Se = 69.2%, and Sp = 87.9%. These results indicate that audio recordings could be used in screening for OSA, but are generally under sensitive. PMID- 26380259 TI - Predicting Fatigue and Psychophysiological Test Performance from Speech for Safety-Critical Environments. AB - Automatic systems for estimating operator fatigue have application in safety critical environments. A system which could estimate level of fatigue from speech would have application in domains where operators engage in regular verbal communication as part of their duties. Previous studies on the prediction of fatigue from speech have been limited because of their reliance on subjective ratings and because they lack comparison to other methods for assessing fatigue. In this paper, we present an analysis of voice recordings and psychophysiological test scores collected from seven aerospace personnel during a training task in which they remained awake for 60 h. We show that voice features and test scores are affected by both the total time spent awake and the time position within each subject's circadian cycle. However, we show that time spent awake and time-of-day information are poor predictors of the test results, while voice features can give good predictions of the psychophysiological test scores and sleep latency. Mean absolute errors of prediction are possible within about 17.5% for sleep latency and 5-12% for test scores. We discuss the implications for the use of voice as a means to monitor the effects of fatigue on cognitive performance in practical applications. PMID- 26380258 TI - Isolation of Extracellular Polymeric Substances from Biofilms of the Thermoacidophilic Archaeon Sulfolobus acidocaldarius. AB - Extracellular polymeric substances (EPS) are the major structural and functional components of microbial biofilms. The aim of this study was to establish a method for EPS isolation from biofilms of the thermoacidophilic archaeon, Sulfolobus acidocaldarius, as a basis for EPS analysis. Biofilms of S. acidocaldarius were cultivated on the surface of gellan gum-solidified Brock medium at 78 degrees C for 4 days. Five EPS extraction methods were compared, including shaking of biofilm suspensions in phosphate buffer, cation-exchange resin (CER) extraction, and stirring with addition of EDTA, crown ether, or NaOH. With respect to EPS yield, impact on cell viability, and compatibility with subsequent biochemical analysis, the CER extraction method was found to be the best suited isolation procedure resulting in the detection of carbohydrates and proteins as the major constituents and DNA as a minor component of the EPS. Culturability of CER treated cells was not impaired. Analysis of the extracellular proteome using two dimensional gel electrophoresis resulted in the detection of several hundreds of protein spots, mainly with molecular masses of 25-116 kDa and pI values of 5-8. Identification of proteins suggested a cytoplasmic origin for many of these proteins, possibly released via membrane vesicles or biofilm-inherent cell lysis during biofilm maturation. Functional analysis of EPS proteins, using fluorogenic substrates as well as zymography, demonstrated the activity of diverse enzyme classes, such as proteases, lipases, esterases, phosphatases, and glucosidases. In conclusion, the CER extraction method, as previously applied to bacterial biofilms, also represents a suitable method for isolation of water soluble EPS from the archaeal biofilms of S. acidocaldarius, allowing the investigation of composition and function of EPS components in these types of biofilms. PMID- 26380257 TI - Direct and Propagated Effects of Small Molecules on Protein-Protein Interaction Networks. AB - Networks of protein-protein interactions (PPIs) link all aspects of cellular biology. Dysfunction in the assembly or dynamics of PPI networks is a hallmark of human disease, and as such, there is growing interest in the discovery of small molecules that either promote or inhibit PPIs. PPIs were once considered undruggable because of their relatively large buried surface areas and difficult topologies. Despite these challenges, recent advances in chemical screening methodologies, combined with improvements in structural and computational biology have made some of these targets more tractable. In this review, we highlight developments that have opened the door to potent chemical modulators. We focus on how allostery is being used to produce surprisingly robust changes in PPIs, even for the most challenging targets. We also discuss how interfering with one PPI can propagate changes through the broader web of interactions. Through this analysis, it is becoming clear that a combination of direct and propagated effects on PPI networks is ultimately how small molecules re-shape biology. PMID- 26380260 TI - Surface-Bound Molecular Gradients for the High-Throughput Screening of Cell Responses. AB - Chemical gradient surfaces are described as surfaces with a gradually varying composition along their length. Continuous chemical gradients have recently been proposed as an alternative to discrete microarrays for the high-throughput screening of the effects of ligand concentration in cells. Here, we review some of the most recent examples in which gradients have been used to evaluate the effect of a varying ligand concentration in cell adhesion, morphology, growth, and differentiation of cells, including some of our recent findings. They show the importance of the organization of ligands at the nanoscale, which is highlighted by abrupt changes in cell behavior at critical concentration thresholds. PMID- 26380261 TI - Focus on the Controversial Aspects of (64)Cu-ATSM in Tumoral Hypoxia Mapping by PET Imaging. AB - Mapping tumor hypoxia is a great challenge in positron emission tomography (PET) imaging as the precise functional information of the biological processes is needed for many effective therapeutic strategies. Tumor hypoxia has been widely reported as a poor prognostic indicator and is often associated with tumor aggressiveness, chemo- and radio-resistance. An accurate diagnosis of hypoxia is a challenge and is crucial for providing accurate treatment for patients' survival benefits. This challenge has led to the emergence of new and novel PET tracers for the functional and metabolic characterization of tumor hypoxia non invasively. Among these tracers, copper semicarbazone compound [64Cu]-diacetyl bis(N (4)-methylthiosemicarbazone) (=64Cu-ATSM) has been developed as a tracer for hypoxia imaging. This review focuses on 64Cu-ATSM PET imaging and the concept is presented in two sections. The first section describes its in vitro development and pre-clinical testing and particularly its affinity in different cell lines. The second section describes the controversial reports on its specificity for hypoxia imaging. The review concludes that 64Cu-ATSM - more than a hypoxic tracer, exhibits tracer accumulation in tumor, which is linked to the redox potential and reactive oxygen species. The authors concluded that 64Cu ATSNM is a marker of over-reduced cell state and thus an indirect marker for hypoxia imaging. The affinity of 64Cu-ATSM for over-reduced cells was observed to be a complex phenomenon. And to provide a definitive and convincing mechanism, more in vivo studies are needed to prove the diagnostic utility of 64Cu-ATSM. PMID- 26380262 TI - Chronic Kidney Disease and Fibrosis: The Role of Uremic Retention Solutes. AB - Chronic kidney disease (CKD) is a major global health concern, and the uremic state is highly associated with fibrogenesis in several organs and tissues. Fibrosis is characterized by excessive production and deposition of extracellular matrix proteins with a detrimental impact on organ function. Another key feature of CKD is the retention and subsequent accumulation of solutes that are normally cleared by the healthy kidney. Several of these uremic retention solutes, including indoxyl sulfate and p-cresyl sulfate, have been suggested to be CKD specific triggers for the development and perpetuation of fibrosis. The purpose of this brief review is to gather and discuss the current body of evidence linking uremic retention solutes to the fibrotic response during CKD, with a special emphasis on the pathophysiological mechanisms in the kidney. PMID- 26380263 TI - Using mHealth to Improve Usage of Antenatal Care, Postnatal Care, and Immunization: A Systematic Review of the Literature. AB - Mobile health (mHealth) technologies have been implemented in many low- and middle-income countries to address challenges in maternal and child health. Many of these technologies attempt to influence patients', caretakers', or health workers' behavior. The purpose of this study was to conduct a systematic review of the literature to determine what evidence exists for the effectiveness of mHealth tools to increase the coverage and use of antenatal care (ANC), postnatal care (PNC), and childhood immunizations through behavior change in low- and middle-income countries. The full text of 53 articles was reviewed and 10 articles were identified that met all inclusion criteria. The majority of studies used text or voice message reminders to influence patient behavior change (80%, n = 8) and most were conducted in African countries (80%, n = 8). All studies showed at least some evidence of effectiveness at changing behavior to improve antenatal care attendance, postnatal care attendance, or childhood immunization rates. However, many of the studies were observational and further rigorous evaluation of mHealth programs is needed in a broader variety of settings. PMID- 26380264 TI - Endogenous Asymmetric Dimethylarginine Pathway in High Altitude Adapted Yaks. AB - Hypoxia-induced and high altitude pulmonary hypertension are a major problem in the mountain areas of the world. The asymmetric methylarginines (ADMA) inhibit nitric oxide (NO) synthesis by competing with L-arginine, and high levels of plasma ADMA predict adverse outcomes in pulmonary hypertension. However, little is known about the regulation of the ADMA-NO pathway in animals adapted to high altitudes. We measured the plasma ADMA concentration, endothelial NO synthase (eNOS), dimethylarginine dimethylaminohydrolases (DDAH) protein expression, and DDAH activities in the lungs from yaks. Although the yaks are hypoxemic, cardiac function and pulmonary arterial pressures are almost normal, and we found decreased DDAH expression and activity in association with reduced plasma ADMA concentrations. The eNOS expression was significantly higher in yaks. These results indicate that augmented endogenous NO activity in yaks through the ADMA DDAH pathway and eNOS upregulation account for the low pulmonary vascular tone observed in high altitude adapted yaks. PMID- 26380265 TI - Relationship of Baseline Hemoglobin Level with Serum Ferritin, Postphlebotomy Hemoglobin Changes, and Phlebotomy Requirements among HFE C282Y Homozygotes. AB - Objectives. We aimed to examine whether baseline hemoglobin levels in C282Y homozygous patients are related to the degree of serum ferritin (SF) elevation and whether patients with different baseline hemoglobin have different phlebotomy requirements. Methods. A total of 196 patients (124 males and 72 females) who had undergone therapeutic phlebotomy and had SF and both pre- and posttreatment hemoglobin values were included in the study. Results. Bivariate correlation analysis suggested that baseline SF explains approximately 6 to 7% of the variation in baseline hemoglobin. The results also showed that males who had higher (>=150 g/L) baseline hemoglobin levels had a significantly greater reduction in their posttreatment hemoglobin despite requiring fewer phlebotomies to achieve iron depletion than those who had lower (<150 g/L) baseline hemoglobin, regardless of whether baseline SF was below or above 1000 ug/L. There were no significant differences between hemoglobin subgroups regarding baseline and treatment characteristics, except for transferrin saturation between male subgroups with SF above 1000 ug/L. Similar differences were observed when females with higher (>=138 g/L) baseline hemoglobin were compared with those with lower (<138 g/L) baseline hemoglobin. Conclusion. Dividing C282Y-homozygous patients into just two subgroups according to the degree of baseline SF elevation may obscure important subgroup variations. PMID- 26380266 TI - In Vivo Anti-Candida Activity of Phenolic Extracts and Compounds: Future Perspectives Focusing on Effective Clinical Interventions. AB - Candida species have increasingly deserved a special attention among the medical community. In spite of the presence of Candida species as a human commensal, alarming rates of local and systemic infections have been observed, varying from moderate to severe impact. Currently available antifungal drugs have progressively lost their effectiveness, pointing urgently the problem of the microorganisms with acquired-resistance. Natural matrices are secularly used for numerous purposes, being inclusive and highly effective as antimicrobials. Increasing evidence gives a particular emphasis to the contribution of phenolic extracts and related individual compounds. In vitro studies clearly confirm their prominent effects, but the confirmation through in vivo studies, including the involved mechanisms of action, is not so much deepened. Therefore, the present report aims to provide extensive knowledge about all these aspects, highlighting the most efficient phytochemical formulations, including therapeutic doses. Further studies need to be incited to deepen knowledge on this area, namely, focused on clinical trials to provide safer and more effective antimicrobials than the current ones. PMID- 26380267 TI - The Combinational Polymorphisms of ORAI1 Gene Are Associated with Preventive Models of Breast Cancer in the Taiwanese. AB - The ORAI calcium release-activated calcium modulator 1 (ORAI1) has been proven to be an important gene for breast cancer progression and metastasis. However, the protective association model between the single nucleotide polymorphisms (SNPs) of ORAI1 gene was not investigated. Based on a published data set of 345 female breast cancer patients and 290 female controls, we used a particle swarm optimization (PSO) algorithm to identify the possible protective models of breast cancer association in terms of the SNPs of ORAI1 gene. Results showed that the PSO-generated models of 2-SNP (rs12320939-TT/rs12313273-CC), 3-SNP (rs12320939 TT/rs12313273-CC/rs712853-(TT/TC)), 4-SNP (rs12320939-TT/rs12313273-CC/rs7135617 (GG/GT)/rs712853-(TT/TC)), and 5-SNP (rs12320939-TT/rs12313273-CC/rs7135617 (GG/GT)/rs6486795-CC/rs712853-(TT/TC)) displayed low values of odds ratios (0.409 0.425) for breast cancer association. Taken together, these results suggested that our proposed PSO strategy is powerful to identify the combinational SNPs of rs12320939, rs12313273, rs7135617, rs6486795, and rs712853 of ORAI1 gene with a strongly protective association in breast cancer. PMID- 26380268 TI - PE Teacher and Classmate Support in Level of Physical Activity: The Role of Sex and BMI Status in Adolescents from Kosovo. AB - The aim of this paper is to examine the role of physical education (PE) teacher and classmate support in relation to sex and BMI status in adolescents' physical activity (PA) in Kosovo. A Classmate and Teacher Support Scale (with additional questions) was used on a cross-sectional sample of 608 girls and 620 boys aged 15 18, randomly selected from secondary schools of seven major municipalities in Kosovo. PA level was determined with a Physical Activity Screening Measure questionnaire. Descriptive statistics and a three-way ANOVA, along with Tukey's HSD post hoc test, were employed. The findings showed the levels of teacher and classmate support to be important factors in stimulating adolescents' PA. It was found that boys with normal weight, high support from teachers, and medium or high support from classmates were more physically active, compared with girls. PMID- 26380269 TI - Promotion and Prevention Focused Feeding Strategies: Exploring the Effects on Healthy and Unhealthy Child Eating. AB - There is a general lack of research addressing the motivations behind parental use of various feeding practices. Therefore, the present work aims to extend the current literature on parent-child feeding interactions by integrating the traditional developmental psychological perspective on feeding practices with elements of Regulatory Focus Theory (RFT) derived from the field of motivational psychology. In this paper, we seek to explain associations between parental feeding practices and child (un)healthy eating behaviors by categorizing parental feeding practices into promotion and prevention focused strategies, thus exploring parent-child feeding interactions within the framework of RFT. Our analyses partly supported the idea that (1) child healthy eating is positively associated with feeding practices characterized as promotion focused, and (2) child unhealthy eating is negatively associated with feeding practices characterized as prevention focused. However, a general observation following from our results suggests that parents' major driving forces behind reducing children's consumption of unhealthy food items and increasing their consumption of healthy food items are strategies that motivate rather than restrict. In particular, parents' provision of a healthy home food environment seems to be essential for child eating. PMID- 26380270 TI - MetaRNA-Seq: An Interactive Tool to Browse and Annotate Metadata from RNA-Seq Studies. AB - The number of RNA-Seq studies has grown in recent years. The design of RNA-Seq studies varies from very simple (e.g., two-condition case-control) to very complicated (e.g., time series involving multiple samples at each time point with separate drug treatments). Most of these publically available RNA-Seq studies are deposited in NCBI databases, but their metadata are scattered throughout four different databases: Sequence Read Archive (SRA), Biosample, Bioprojects, and Gene Expression Omnibus (GEO). Although the NCBI web interface is able to provide all of the metadata information, it often requires significant effort to retrieve study- or project-level information by traversing through multiple hyperlinks and going to another page. Moreover, project- and study-level metadata lack manual or automatic curation by categories, such as disease type, time series, case control, or replicate type, which are vital to comprehending any RNA-Seq study. Here we describe "MetaRNA-Seq," a new tool for interactively browsing, searching, and annotating RNA-Seq metadata with the capability of semiautomatic curation at the study level. PMID- 26380271 TI - A Universal Mental Health Promotion Programme for Young People in Italy. AB - In Italy, the Mental Health Unit of the National Institute of Public Health has developed a school-based mental health programme based on a structured handbook. The aim of this programme is to promote self-efficacy, psychological well-being, and life satisfaction. In this study, we evaluated the effectiveness of this programme. We used data from 308 students who participated in a study in 9 Italian high schools during the 2011-2012 school year. In order to analyse the school intervention programme, we set up a pre-post test design study involving 18 classrooms (8 of which acting as a control). The schools were selected via a snowball technique, and then the classrooms that agreed to participate were randomly assigned to intervention and control groups. The programme was performed during regular school hours in one-hour a week sessions for a total of 20 hours of classroom time. Assessments before and 2 months after the programme were performed using Regulatory Emotional Self-Efficacy, Satisfaction With Life, and Ryff's Psychological Well-Being Scales. The results showed an improvement in self efficacy in regulating negative affect, overall psychological well-being, and satisfaction with life. These results demonstrate that the programme produced significant positive effects on the mental health status of participating students. PMID- 26380272 TI - Text Mining for Translational Bioinformatics. PMID- 26380274 TI - Muscular Dystrophy: Disease Mechanisms and Therapies. PMID- 26380273 TI - Transcriptional Pathways Associated with Skeletal Muscle Changes after Spinal Cord Injury and Treadmill Locomotor Training. AB - The genetic and molecular events associated with changes in muscle mass and function after SCI and after the implementation of candidate therapeutic approaches are still not completely known. The overall objective of this study was to identify key molecular pathways activated with muscle remodeling after SCI and locomotor training. We implemented treadmill training in a well-characterized rat model of moderate SCI and performed genome wide expression profiling on soleus muscles at multiple time points: 3, 8, and 14 days after SCI. We found that the activity of the protein ubiquitination and mitochondrial function related pathways was altered with SCI and corrected with treadmill training. The BMP pathway was differentially activated with early treadmill training as shown by Ingenuity Pathway Analysis. The expression of several muscle mass regulators was modulated by treadmill training, including Fst, Jun, Bmpr2, Actr2b, and Smad3. In addition, key players in fatty acids metabolism (Lpl and Fabp3) responded to both SCI induced inactivity and reloading with training. The decrease in Smad3 and Fst early after the initiation of treadmill training was confirmed by RT-PCR. Our data suggest that TGFbeta/Smad3 signaling may be mainly involved in the decrease in muscle mass observed with SCI, while the BMP pathway was activated with treadmill training. PMID- 26380275 TI - Simultaneous Labyrinthectomy and Cochlear Implantation for Patients with Single Sided Meniere's Disease and Profound Sensorineural Hearing Loss. AB - Objective. To investigate the treatment outcome of a simultaneous labyrinthectomy and cochlear implantation in patients with single-sided Meniere's disease and profound sensorineural hearing loss. Study Design. Prospective study. Method. Five patients with single-sided Meniere's disease with active vertigo and functional deafness were included. In all cases, simultaneous cochlear implantation combined with labyrinthectomy surgery was performed. The outcome has been evaluated by the Dizziness Handicap Inventory (DHI) and speech recognition. Results. The combined labyrinthectomy and cochlear implantation led in all patients to a highly significant reduction of dizziness up to a restitutio ad integrum. After activation of the cochlear implant and rehabilitation, a mean monosyllabic speech understanding of 69% at 65 dB was observed. Conclusion. For patients with single-sided Meniere's disease and profound sensorineural hearing loss the simultaneous labyrinthectomy and cochlear implantation are efficient method for the treatment of vertigo as well as the rehabilitation of the auditory system. PMID- 26380276 TI - One-Year Results of the BeweegKuur Lifestyle Intervention Implemented in Dutch Primary Healthcare Settings. AB - Background. Lifestyle interventions focusing on healthy diet and physical activity (PA) are effective in reducing health risks in controlled research settings. The aim of this study was to investigate the one-year results of the BeweegKuur lifestyle intervention implemented nationwide in Netherlands for people with a weight-related health risk. Materials and Methods. Data were requested from all 160 locations participating in the BeweegKuur. In a one group pretest/posttest study, one-year changes in health outcome variables and time spent on physical activity were tested with dependent t-tests. Associations between one-year changes in weight and waist circumference and sociodemographic factors and uptake of the program were analysed with ANOVA. Results. Data for 517 participants from 47 locations were available for analysis. One year after the intervention, weight reduced by 2.9 kg (95% CI -3.3;, -2.5), waist circumference by 4.3 cm (-4.9; -3.7), and blood glucose by 0.5 mmol/L (-0.8; -0.3). Physical activity increased significantly. Higher uptake of the program was associated with a larger decrease in waist circumference. Conclusion. The results of the study suggest that lifestyle interventions implemented in real-life primary healthcare settings with tailor-made supervision can contribute meaningfully to primary prevention. PMID- 26380277 TI - Facilitators and Barriers to Health-Seeking Behaviours among Filipino Migrants: Inductive Analysis to Inform Health Promotion. AB - Understanding factors that influence health-seeking behaviour of migrants is necessary to intervene for behaviour change. This paper explores Filipino migrants' perceptions of facilitators and barriers to maintaining health in Australia. Open-ended survey item responses reflecting factors that assisted and hindered health following migration to Australia were inductively analysed. Three hundred and thirty-seven of the 552 survey respondents (61%) provided open-ended responses. Responses were grouped into two major categories: individual factors, including personal resources and cultural influences, and environmental factors encompassing both the physical conditions in the host country and health service access. Awareness of practices that enhance health was a major personal facilitator of health-seeking behaviour; however, competing priorities of daily living were perceived as barriers. Cultural beliefs and practices influenced health-seeking behaviour. Despite high self-rated English language skills in this population, new migrants and the elderly cited communication difficulties as barriers to accessing health services. Insight into facilitators and barriers to health-seeking behaviour in this less researched migrant population revealed tools for enhancing engagement in health promotion programs addressing healthy lifestyle. PMID- 26380278 TI - A Data Hiding Technique to Synchronously Embed Physiological Signals in H.264/AVC Encoded Video for Medicine Healthcare. AB - The recognition of clinical manifestations in both video images and physiological signal waveforms is an important aid to improve the safety and effectiveness in medical care. Physicians can rely on video-waveform (VW) observations to recognize difficult-to-spot signs and symptoms. The VW observations can also reduce the number of false positive incidents and expand the recognition coverage to abnormal health conditions. The synchronization between the video images and the physiological-signal waveforms is fundamental for the successful recognition of the clinical manifestations. The use of conventional equipment to synchronously acquire and display the video-waveform information involves complex tasks such as the video capture/compression, the acquisition/compression of each physiological signal, and the video-waveform synchronization based on timestamps. This paper introduces a data hiding technique capable of both enabling embedding channels and synchronously hiding samples of physiological signals into encoded video sequences. Our data hiding technique offers large data capacity and simplifies the complexity of the video-waveform acquisition and reproduction. The experimental results revealed successful embedding and full restoration of signal's samples. Our results also demonstrated a small distortion in the video objective quality, a small increment in bit-rate, and embedded cost savings of 2.6196% for high and medium motion video sequences. PMID- 26380279 TI - Data Acquisition and Processing in Biology and Medicine. PMID- 26380280 TI - Socioeconomic Impact on the Prevalence of Cardiovascular Risk Factors in Wallonia, Belgium: A Population-Based Study. AB - Background. Monitoring the epidemiology of cardiovascular risk factors (CRFs) and their determinants is important to develop appropriate recommendations to prevent cardiovascular diseases in specific risk groups. The NESCaV study was designed to collect standardized data to estimate the prevalence of CRFs in relation to socioeconomic parameters among the general adult population in the province of Liege, Wallonia, Belgium. Methods. A representative stratified random sample of 1017 subjects, aged 20-69 years, participated in the NESCaV study (2010-2012). A self-administered questionnaire, a clinical examination, and laboratory tests were performed on participants. CRFs included hypertension, dyslipidemia, global obesity, abdominal obesity, diabetes, current smoking, and physical inactivity. Covariates were education and subjective and objective socioeconomic levels. Data were analyzed by weighted logistic regression. Results. The prevalence of hypertension, abdominal obesity, global obesity, current smoking, and physical inactivity was higher in subjects with low education and who considered themselves "financially in need." Living below poverty threshold also increased the risk of global and abdominal obesity, current smoking, and physical inactivity. Conclusion. The study shows that socioeconomic factors impact the prevalence of CRFs in the adult population of Wallonia. Current public health policies should be adjusted to reduce health inequalities in specific risk groups. PMID- 26380281 TI - Tennis Elbow Diagnosis Using Equivalent Uniform Voltage to Fit the Logistic and the Probit Diseased Probability Models. AB - To develop the logistic and the probit models to analyse electromyographic (EMG) equivalent uniform voltage- (EUV-) response for the tenderness of tennis elbow. In total, 78 hands from 39 subjects were enrolled. In this study, surface EMG (sEMG) signal is obtained by an innovative device with electrodes over forearm region. The analytical endpoint was defined as Visual Analog Score (VAS) 3+ tenderness of tennis elbow. The logistic and the probit diseased probability (DP) models were established for the VAS score and EMG absolute voltage-time histograms (AVTH). TV50 is the threshold equivalent uniform voltage predicting a 50% risk of disease. Twenty-one out of 78 samples (27%) developed VAS 3+ tenderness of tennis elbow reported by the subject and confirmed by the physician. The fitted DP parameters were TV50 = 153.0 mV (CI: 136.3-169.7 mV), gamma 50 = 0.84 (CI: 0.78-0.90) and TV50 = 155.6 mV (CI: 138.9-172.4 mV), m = 0.54 (CI: 0.49-0.59) for logistic and probit models, respectively. When the EUV >= 153 mV, the DP of the patient is greater than 50% and vice versa. The logistic and the probit models are valuable tools to predict the DP of VAS 3+ tenderness of tennis elbow. PMID- 26380282 TI - Primary Murine Myotubes as a Model for Investigating Muscular Dystrophy. AB - Muscular dystrophies caused by defects in various genes are often associated with impairment of calcium homeostasis. Studies of calcium currents are hampered because of the lack of a robust cellular model. Primary murine myotubes, formed upon satellite cell fusion, were examined for their utilization as a model of adult skeletal muscle. We enzymatically isolated satellite cells and induced them to differentiation to myotubes. Myotubes displayed morphological and physiological properties resembling adult muscle fibers. Desmin and myosin heavy chain immunoreactivity in the differentiated myotubes were similar to the mature muscle cross-striated pattern. The myotubes responded to electrical and chemical stimulations with sarcoplasmic reticulum calcium release. Presence of L-type calcium channels in the myotubes sarcolemma was confirmed via whole-cell patch clamp technique. To assess the use of myotubes for studying functional mutation effects lentiviral transduction was applied. Satellite cells easily underwent transduction and were able to retain a positive expression of lentivirally encoded GFP up to and after the formation of myotubes, without changes in their physiological and morphological properties. Thus, we conclude that murine myotubes may serve as a fruitful cell model for investigating calcium homeostasis in muscular dystrophy and the effects of gene modifications can be assessed due to lentiviral transduction. PMID- 26380283 TI - Examining the Relationship between Heavy Alcohol Use and Assaults: With Adjustment for the Effects of Unmeasured Confounders. AB - BACKGROUND: Experimental studies suggest that alcohol can lead to aggression in laboratory settings; however, it is impossible to test the causal relationship between alcohol use and real-life violence among humans in randomized clinical trials. Objectives. (i) To examine the relationship between heavy alcohol use and assaults in a population based study; (ii) to demonstrate the proxy outcome method, as a means of controlling the effects of unknown/unmeasured confounders in observational studies. METHODS: This study used data collected from three waves of the National Survey on Drug Use and Health (NSDUH). The effects of heavy alcohol use on assault were measured using multivariable logistic regressions in conjunction with the proxy outcome method. RESULTS: Application of the proxy outcome method indicated that effect sizes of heavy alcohol use on the risk of assault were overestimated in the standard models. After adjusting for the effects of unknown/unmeasured confounders, the risk of assault remained 43% and 63% higher (P < 0.05) among participants who consumed 5+ drinks/day for 5-8 days/month and 9-30 days/month, respectively. CONCLUSIONS: Even after adjustment for unknown/unmeasured confounders the association between heavy alcohol use and risk of violence remained significant. These findings support the hypothesis that heavy alcohol use can cause violence. PMID- 26380284 TI - Behaviour Change in Public Health: Evidence and Implications. PMID- 26380285 TI - Adolescents Perceptions of Pro- and Antitobacco Imagery and Marketing: Qualitative Study of Students from Suva, Fiji. AB - BACKGROUND: Many studies examining smoking uptake among young people in the Pacific have not included their exposure to tobacco control promotions in the media in their assessment. This study examines how Fijian students view tobacco and tobacco-related media depictions to gain insight into both drivers of smoking uptake and potential directions for prevention interventions. METHODS: A sample of thirty Fijian students (15 male and 15 female) aged 14-17 years, was recruited from a Suva school between September and October 2013 and participated in a one to-one in-depth interview about their views on tobacco use, media consumption patterns and preferences and awareness of tobacco use in media. RESULTS: Despite radical developments in access to media, television remains the most popular. Yet, the majority of participants were unaware of any protobacco imagery on television or other entertainment media. Tobacco-related imagery was more likely to be seen in connection with point of sale advertising and branding. The advertising potential of the shop counter was acutely apparent to some participants and this space was considered highly influential. CONCLUSIONS: Despite the fact that the recently introduced graphic health warnings were generally well received, more can be done to extend the use of media for tobacco control benefits in Fiji. PMID- 26380286 TI - Tetramethylpyrazine Inhibits Activation of Hepatic Stellate Cells through Hedgehog Signaling Pathways In Vitro. AB - BACKGROUND AND AIM: Tetramethylpyrazine (TMP), a major alkaloid isolated from Ligusticum chuanxiong, has been reported in hepatic fibrosis models. However, the action mechanism remains unclear. In the present study, effects of tetramethylpyrazine (TMP) against hepatic stellate cell (HSC) activation as well as the possible mechanisms were evaluated. METHODS: Western blot assay was used to detect TMP effects on protein expression of Smo, Patched, Hhip, and Gli and to investigate the effects of TMP on Cyclin D1, Cyclin E1, CDK2, Bcl-2, Bax, and caspase expression with cyclopamine supplementation. RESULTS: Our results showed that TMP significantly inhibits the expression of Cyclin D1, Cyclin E1, and Cyclin-dependent kinase CDK2 and changes the HSC cycle by inhibiting the proliferation of HSC. Moreover, TMP has also been shown to decrease the expression of Bcl-2 and increase the expression of Bax in HSC-T6 cells. Furthermore, TMP can inhibit the expression of connective tissue growth factor (CTGF), and the inhibitory effect was intensified after the application of joint treatment with TMP and cyclopamine. CONCLUSION: TMP may be an effective Hh signaling pathway inhibitor for hepatic fibrosis treatment. PMID- 26380287 TI - Screening of the Seed Region of MIR184 in Keratoconus Patients from Saudi Arabia. AB - Micro-RNAs (miRNAs) are regulators of gene expression that control various biological processes. The role of many identified miRNAs is not yet resolved. Recent evidence suggests that miRNA mutations and/or misexpression may contribute to genetic disorders. Point mutations in the seed region of MIR184 have been recently identified in Keratoconus (KC) patients with or without other corneal and lens abnormalities. We investigated mutations within MIR184 in KC patients from Saudi Arabia and examined the relative expression of miR-184 and miR-205 in human cornea. Ethnically matched KC cases (n = 134) were recruited and sequencing was performed using PCR-based Sanger sequencing and analyzed using the Sequencher 5.2 software. Expression of miR-184 and miR-205 was profiled in postmortem unaffected ocular tissues obtained from donors with no history of ocular diseases. miR-184 expression was 15-fold higher than that of miR-205 in cornea samples. No mutation(s) within the screened genomic region of MIR184 in KC cases was detected. This suggests that mutation in MIR184 is a rare cause of KC alone and may be more relevant to cases of KC associated with other ocular abnormalities. The increased expression of miR-184 versus miR-205 in normal cornea samples implies a possible role of miR184 in cornea development and/or corneal diseases. PMID- 26380288 TI - Khat (Catha edulis Forsk.) Dependence Potential and Pattern of Use in Saudi Arabia. AB - BACKGROUND: Catha edulis Forsk. (Khat) is used for its psychoactive effects among people in Africa and the Arabian Peninsula, although its utilization is illegal in some countries such as Saudi Arabia. This study examined the pattern of Khat use and assessed the applicability of the Drug Abuse Screening Test-10 (DAST-10) to measure Khat dependence. METHODS: A pretested questionnaire was used to gather data from 603 respondents. Variables included demographic characteristics, pattern of use, reasons for Khat chewing, and DAST-10. Stepwise-logistic regression was used to explore predictors of Khat dependence. RESULTS: The majority of the respondents were married, had a secondary school level of education, were employed, were younger than 35 years old, and were living in rural areas. Many chewers gave more than one reason for using Khat. It was mainly used to increase mental capacity, physical strength, and social entertainment, as well as enhance cheerfulness and orgasms. Statistical modeling of Khat dependence suggested that the most significant predictors were residence (OR = 1.67, P < 0.02), frequency of Khat chewing (OR = 4.8, P < 0.01), age of starting Khat chewing (OR = 1.15, P < 0.01), and time of Khat effect (OR = 1.15, P < 0.04). CONCLUSION: Our study provides important information on the pattern of Khat use and its potential to cause dependence. PMID- 26380289 TI - Genetic Engineering of Dystroglycan in Animal Models of Muscular Dystrophy. AB - In skeletal muscle, dystroglycan (DG) is the central component of the dystrophin glycoprotein complex (DGC), a multimeric protein complex that ensures a strong mechanical link between the extracellular matrix and the cytoskeleton. Several muscular dystrophies arise from mutations hitting most of the components of the DGC. Mutations within the DG gene (DAG1) have been recently associated with two forms of muscular dystrophy, one displaying a milder and one a more severe phenotype. This review focuses specifically on the animal (murine and others) model systems that have been developed with the aim of directly engineering DAG1 in order to study the DG function in skeletal muscle as well as in other tissues. In the last years, conditional animal models overcoming the embryonic lethality of the DG knock-out in mouse have been generated and helped clarifying the crucial role of DG in skeletal muscle, while an increasing number of studies on knock-in mice are aimed at understanding the contribution of single amino acids to the stability of DG and to the possible development of muscular dystrophy. PMID- 26380290 TI - Identification and Progression of Heart Disease Risk Factors in Diabetic Patients from Longitudinal Electronic Health Records. AB - Heart disease is the leading cause of death worldwide. Therefore, assessing the risk of its occurrence is a crucial step in predicting serious cardiac events. Identifying heart disease risk factors and tracking their progression is a preliminary step in heart disease risk assessment. A large number of studies have reported the use of risk factor data collected prospectively. Electronic health record systems are a great resource of the required risk factor data. Unfortunately, most of the valuable information on risk factor data is buried in the form of unstructured clinical notes in electronic health records. In this study, we present an information extraction system to extract related information on heart disease risk factors from unstructured clinical notes using a hybrid approach. The hybrid approach employs both machine learning and rule-based clinical text mining techniques. The developed system achieved an overall microaveraged F-score of 0.8302. PMID- 26380291 TI - Supervised Learning Based Hypothesis Generation from Biomedical Literature. AB - Nowadays, the amount of biomedical literatures is growing at an explosive speed, and there is much useful knowledge undiscovered in this literature. Researchers can form biomedical hypotheses through mining these works. In this paper, we propose a supervised learning based approach to generate hypotheses from biomedical literature. This approach splits the traditional processing of hypothesis generation with classic ABC model into AB model and BC model which are constructed with supervised learning method. Compared with the concept cooccurrence and grammar engineering-based approaches like SemRep, machine learning based models usually can achieve better performance in information extraction (IE) from texts. Then through combining the two models, the approach reconstructs the ABC model and generates biomedical hypotheses from literature. The experimental results on the three classic Swanson hypotheses show that our approach outperforms SemRep system. PMID- 26380292 TI - Risk Factors for Development of Septic Shock in Patients with Urinary Tract Infection. AB - INTRODUCTION: Severe sepsis and septic shock are associated with substantial mortality. However, few studies have assessed the risk of septic shock among patients who suffered from urinary tract infection (UTI). MATERIALS AND METHODS: This retrospective study recruited UTI cases from an acute care hospital between January 2006 and October 2012 with prospective data collection. RESULTS: Of the 710 participants admitted for UTI, 80 patients (11.3%) had septic shock. The rate of bacteremia is 27.9%; acute kidney injury is 12.7%, and the mortality rate is 0.28%. Multivariable logistic regression analyses indicated that coronary artery disease (CAD) (OR: 2.521, 95% CI: 1.129-5.628, P = 0.024), congestive heart failure (CHF) (OR: 4.638, 95% CI: 1.908-11.273, P = 0.001), and acute kidney injury (AKI) (OR: 2.992, 95% CI: 1.610-5.561, P = 0.001) were independently associated with septic shock in patients admitted with UTI. In addition, congestive heart failure (female, OR: 4.076, 95% CI: 1.355-12.262, P = 0.012; male, OR: 5.676, 95% CI: 1.103-29.220, P = 0.038, resp.) and AKI (female, OR: 2.995, 95% CI: 1.355-6.621, P = 0.007; male, OR: 3.359, 95% CI: 1.158-9.747, P = 0.026, resp.) were significantly associated with risk of septic shock in both gender groups. CONCLUSION: This study showed that patients with a medical history of CAD or CHF have a higher risk of shock when admitted for UTI treatment. AKI, a complication of UTI, was also associated with septic shock. Therefore, prompt and aggressive management is recommended for those with higher risks to prevent subsequent treatment failure in UTI patients. PMID- 26380293 TI - Effects of a Health Promotion Program Based on a Train-the-Trainer Approach on Quality of Life and Mental Health of Long-Term Unemployed Persons. AB - BACKGROUND: Long-term unemployment is associated with poorer mental health. The aim of this study was to evaluate the effectiveness of a health promotion program using the train-the-trainer approach on health-related quality of life (HRQoL) and mental health of long-term unemployed persons. METHODS: A prospective parallel-group study was conducted among 365 long-term unemployed persons. 287 participants (179 members of the intervention group IG and 108 members of the control group) were reassessed after three months. The intervention comprised both individual sessions based on Motivational Interviewing and participatory group sessions; no health promotion program was administered in the control group. The endpoints were HRQoL (SF-12), depression, and anxiety. The effect size of the change across time in the IG and CG was measured by Cohen's d. To assess the significance of group differences in the change across time, a random effects model was used. RESULTS: Within three months HRQoL improved and anxiety and depression decreased significantly in the IG. A significant intervention effect was observed for anxiety (p = 0.012). Effect sizes in the IG were small to moderate in terms of Cohen's d (anxiety: d = -0.33; SF-12 mental: d = 0.31; depression: d = -0.25; SF-12 physical: d = 0.19). CONCLUSIONS: The health promotion program, based on a train-the-trainer approach, showed positive effects on HRQoL and mental health, especially anxiety, of long-term unemployed persons, a highly burdened target group where an improvement in mental health is a crucial prerequisite to social participation and successful reintegration into the job market. PMID- 26380294 TI - Automatic Artifact Removal from Electroencephalogram Data Based on A Priori Artifact Information. AB - Electroencephalogram (EEG) is susceptible to various nonneural physiological artifacts. Automatic artifact removal from EEG data remains a key challenge for extracting relevant information from brain activities. To adapt to variable subjects and EEG acquisition environments, this paper presents an automatic online artifact removal method based on a priori artifact information. The combination of discrete wavelet transform and independent component analysis (ICA), wavelet-ICA, was utilized to separate artifact components. The artifact components were then automatically identified using a priori artifact information, which was acquired in advance. Subsequently, signal reconstruction without artifact components was performed to obtain artifact-free signals. The results showed that, using this automatic online artifact removal method, there were statistical significant improvements of the classification accuracies in both two experiments, namely, motor imagery and emotion recognition. PMID- 26380295 TI - Gene Network Analysis of Glucose Linked Signaling Pathways and Their Role in Human Hepatocellular Carcinoma Cell Growth and Survival in HuH7 and HepG2 Cell Lines. AB - Cancer progression may be affected by metabolism. In this study, we aimed to analyze the effect of glucose on the proliferation and/or survival of human hepatocellular carcinoma (HCC) cells. Human gene datasets regulated by glucose were compared to gene datasets either dysregulated in HCC or regulated by other signaling pathways. Significant numbers of common genes suggested putative involvement in transcriptional regulations by glucose. Real-time proliferation assays using high (4.5 g/L) versus low (1 g/L) glucose on two human HCC cell lines and specific inhibitors of selected pathways were used for experimental validations. High glucose promoted HuH7 cell proliferation but not that of HepG2 cell line. Gene network analyses suggest that gene transcription by glucose could be mediated at 92% through ChREBP in HepG2 cells, compared to 40% in either other human cells or rodent healthy liver, with alteration of LKB1 (serine/threonine kinase 11) and NOX (NADPH oxidases) signaling pathways and loss of transcriptional regulation of PPARGC1A (peroxisome-proliferator activated receptors gamma coactivator 1) target genes by high glucose. Both PPARA and PPARGC1A regulate transcription of genes commonly regulated by glycolysis, by the antidiabetic agent metformin and by NOX, suggesting their major interplay in the control of HCC progression. PMID- 26380296 TI - Secular Changes of Adiposity and Motor Development in Czech Preschool Children: Lifestyle Changes in Fifty-Five Year Retrospective Study. AB - Secular trends of adiposity and motor development in preschool children since the fifties of the last century up to the beginning of this millennium were analyzed so as to reveal possible changes due to continuously differentiating lifestyle. In preschool children (n = 3678) height, weight, skinfold thickness over triceps, subscapular, and suprailiac were measured by Harpenden caliper in 1957, 1977, 1980, 1985, 1990, and 2012. Simultaneously, motor performance was tested by evaluating the achievements in broad jump and throwing a ball, as a marker of adaptation to changing level of physical activity, free games, and exercise. Along the period of five decades the values of skinfold thickness increased significantly until 2012, mainly on the trunk. Simultaneously, the level of motor performance significantly decreased. Modifications of the way of life during the mentioned five decades characterized by sedentarism and inadequate food intake as related to energy output influenced negatively both adiposity and motor performance already in preschool children. Mostly increased deposition of fat on the trunk which is considered as a marker of possible development of metabolic syndrome was apparent already in preschool age, indicating the importance of early intervention concerning also physical activity and availability for exercise since early life. PMID- 26380297 TI - Information-Theoretical Quantifier of Brain Rhythm Based on Data-Driven Multiscale Representation. AB - This paper presents a data-driven multiscale entropy measure to reveal the scale dependent information quantity of electroencephalogram (EEG) recordings. This work is motivated by the previous observations on the nonlinear and nonstationary nature of EEG over multiple time scales. Here, a new framework of entropy measures considering changing dynamics over multiple oscillatory scales is presented. First, to deal with nonstationarity over multiple scales, EEG recording is decomposed by applying the empirical mode decomposition (EMD) which is known to be effective for extracting the constituent narrowband components without a predetermined basis. Following calculation of Renyi entropy of the probability distributions of the intrinsic mode functions extracted by EMD leads to a data-driven multiscale Renyi entropy. To validate the performance of the proposed entropy measure, actual EEG recordings from rats (n = 9) experiencing 7 min cardiac arrest followed by resuscitation were analyzed. Simulation and experimental results demonstrate that the use of the multiscale Renyi entropy leads to better discriminative capability of the injury levels and improved correlations with the neurological deficit evaluation after 72 hours after cardiac arrest, thus suggesting an effective diagnostic and prognostic tool. PMID- 26380298 TI - Using a Smartphone Application to Promote Healthy Dietary Behaviours and Local Food Consumption. AB - Smartphone "apps" are a powerful tool for public health promotion, but unidimensional interventions have been ineffective at sustaining behavioural change. Various logistical issues exist in successful app development for health intervention programs and for sustaining behavioural change. This study reports on a smartphone application and messaging service, called "SmartAPPetite," which uses validated behaviour change techniques and a behavioural economic approach to "nudge" users into healthy dietary behaviours. To help gauge participation in and influence of the program, data were collected using an upfront food survey, message uptake tracking, experience sampling interviews, and a follow-up survey. Logistical and content-based issues in the deployment of the messaging service were subsequently addressed to strengthen the effectiveness of the app in changing dietary behaviours. Challenges included creating relevant food goal categories for participants, providing messaging appropriate to self-reported food literacy and ensuring continued participation in the program. SmartAPPetite was effective at creating a sense of improved awareness and consumption of healthy foods, as well as drawing people to local food vendors with greater frequency. This work serves as a storehouse of methods and best practices for multidimensional local food-based smartphone interventions aimed at improving the "triple bottom line" of health, economy, and environment. PMID- 26380299 TI - Tyrosine 705 Phosphorylation of STAT3 Is Associated with Phenotype Severity in TGFbeta1 Transgenic Mice. AB - Transforming growth factor beta 1 (TGFbeta1) is a key player in skeletal muscle degenerative and regenerative processes. We previously showed that conditionally overexpressing TGFbeta1 in skeletal muscles caused myofiber atrophy and endomysial fibrosis in mice. However, the disease severity varied significantly among individual mice. While 40% of mice developed severe muscle pathology and lost body weight within 2 weeks of TGFbeta1 transgene induction in muscles, the rest showed milder or no phenotype. This study aims at determining whether signal transducer and activator of transcription 3 (STAT3) plays a role in the phenotypic difference and whether it can be activated by TGFbeta1 directly in muscle cells. Our results show that while total STAT3 was not differentially expressed between the two groups of mice, there was significantly higher pSTAT3 (Tyr705) in the muscles of the mice with severe phenotype. Immunohistochemistry showed that pSTAT3 (Tyr705) was localized in approximately 50% of the nuclei of the muscles. We further showed that TGFbeta1 induced Tyr705 phosphorylation of STAT3 in C2C12 cells within 30 minutes of treatment while total STAT3 was not affected. Our findings suggest that TGFbeta1 alone can induce Tyr705 phosphorylation of STAT3 in skeletal muscle cells and contribute to disease severity in transgenic TGFbeta1 mice. PMID- 26380300 TI - The Assessment of Oral Microflora Exposed to 3% Ethanolic Extract of Brazilian Green Propolis Preparation Used for Hygiene Maintenance following Minor Oral Surgeries. AB - The aim of this study was to investigate the influence of a topically administered hygienic preparation containing a 3% ethanolic extract of Brazilian green propolis (EEP-B) on oral microflora spectrum changes in a group of patients who underwent common oral surgery procedures. Two gel samples were compared: the tested gel containing an active ingredient, that is, a 3% EEP-B (gel GA), and a placebo as the negative control (gel GC). The collection of microbiological material included 14 patients requiring surgical extraction of wisdom molars and short endosseous implant installation. Clinical examinations were carried out as follow-up, that is, baseline and after 5-6 weeks' time. During the first and subsequent assessment, swabs were taken from the mucosal surface. The number of microorganism species was found to have increased following the application of GC gel over the period of 5-6 weeks. This mainly affected Gram-positive rods and bacilli as well as Gram-negative rods. Application of the GA gel enriched with 3% EEP-B caused a profound reduction in the amount of Neisseria spp. and Bifidobacterium spp. strains. Elimination of seven species of microorganisms was observed: Streptococcus acidominimus, Streptococcus oralis, Staphylococcus epidermidis, Veillonella parvula, Bifidobacterium breve, Bifidobacterium longum, and Lactobacillus acidophilus. PMID- 26380301 TI - Evaluation of Influence of Various Polymers on Dissolution and Phase Behavior of Carbamazepine-Succinic Acid Cocrystal in Matrix Tablets. AB - The aim of current study was to explore the influence of three commonly used polymers, that is, cellulosics and noncellulosics, for example, Methocel K4M, Kollidon VA/64, and Soluplus, on the phase disproportionation and drug release profile of carbamazepine-succinic acid (CBZ-SUC) cocrystal at varying drug to polymer ratios (1 : 1 to 1 : 0.25) in matrix tablets. The polymorphic phase disproportionation during in-depth dissolution studies of CBZ-SUC cocrystals and its crystalline properties were scrutinized by X-ray powder diffractrometry and Raman spectroscopy. The percent drug release from HPMC formulations (CSH) showed inverse relation with the concentration of polymer; that is, drug release increased with decrease in polymer concentration. On contrary, direct relation was observed between percent drug release and polymer concentrations of Kollidon VA 64/Soluplus (CSK, CSS). At similar polymer concentration, drug release from pure carbamazepine was slightly lower with HPMC formulations than that of cocrystal; however, opposite trend in release rate was observed with Kollidon VA/64 and Soluplus. The significant increase in dissolution rate of cocrystal occurred with Kollidon VA/64 and Soluplus at higher polymer concentration. Moreover, no phase change took place in Methocel and Kollidon formulations. No tablet residue was left for Soluplus formulation so the impact of polymer on cocrystal integrity cannot be predicted. PMID- 26380302 TI - Recognition and Evaluation of Clinical Section Headings in Clinical Documents Using Token-Based Formulation with Conditional Random Fields. AB - Electronic health record (EHR) is a digital data format that collects electronic health information about an individual patient or population. To enhance the meaningful use of EHRs, information extraction techniques have been developed to recognize clinical concepts mentioned in EHRs. Nevertheless, the clinical judgment of an EHR cannot be known solely based on the recognized concepts without considering its contextual information. In order to improve the readability and accessibility of EHRs, this work developed a section heading recognition system for clinical documents. In contrast to formulating the section heading recognition task as a sentence classification problem, this work proposed a token-based formulation with the conditional random field (CRF) model. A standard section heading recognition corpus was compiled by annotators with clinical experience to evaluate the performance and compare it with sentence classification and dictionary-based approaches. The results of the experiments showed that the proposed method achieved a satisfactory F-score of 0.942, which outperformed the sentence-based approach and the best dictionary-based system by 0.087 and 0.096, respectively. One important advantage of our formulation over the sentence-based approach is that it presented an integrated solution without the need to develop additional heuristics rules for isolating the headings from the surrounding section contents. PMID- 26380303 TI - Systemic Inflammation in Duchenne Muscular Dystrophy: Association with Muscle Function and Nutritional Status. AB - Inflammation described in patients with Duchenne muscular dystrophy (DMD) may be related to loss of muscle function or to obesity. It is unknown if circulating proinflammatory cytokines (IL-6, IL-1, and TNF-alpha) levels are associated with muscle function. The purpose was to evaluate whether an association exists between systemic inflammation with muscle function and nutritional status in DMD patients. In 66 DMD patients without corticosteroid treatment, the following were evaluated in serum: cytokines (IL-1, IL-6, and TNF-alpha), C-reactive protein (CRP), leptin, adiponectin, and creatine kinase (CK). Muscle function was evaluated using Vignos Scale. Patients with better muscle function had the highest concentration of CK, IL-1, and TNF-alpha compared with less muscle function. No differences in IL-6 and adiponectin concentration were identified among groups with different levels of muscle function. Also, no differences were observed in the concentration of cytokines among groups with different nutritional status levels (underweight, normal weight, and overweight/obese). However, CRP and leptin were increased in the obese group compared with normal and underweight subjects. Systemic inflammation is increased in patients with better muscle function and decreases in DMD patients with poorer muscle function; nevertheless, systemic inflammation is similar among different levels of nutritional status in DMD patients. PMID- 26380304 TI - Comparison of Simultaneous Nitrification and Denitrification for Three Different Reactors. AB - Discharge of high NH4-N containing wastewater into water bodies has become a critical and serious issue due to its negative impact on water and environmental quality. In this research, the performance of three different reactors was assessed and compared with regard to the removal of NH4-N from wastewater. The highest nitrogen removal efficiency of 98.3% was found when the entrapped sludge reactor (ESR), in which the sludge was entrapped in polyethylene glycol polymer, was used. Under intermittent aeration, nitrification and denitrification occurred simultaneously in the aerobic and anaerobic periods. Moreover, internal carbon was consumed efficiently for denitrification. On the other hand, internal carbon consumption was not found to occur in the suspended sludge reactor (SSR) and the mixed sludge reactor (MSR) and this resulted in nitrogen removal efficiencies of SSR and MSR being 64.7 and 45.1%, respectively. Nitrification and denitrification were the main nitrogen removal processes in the aerobic and anaerobic periods, respectively. However, due to the absence of sufficient organic carbon, denitrification was uncompleted resulting in high NO3-N contents in the effluent. PMID- 26380305 TI - Using Photovoice as a Community Based Participatory Research Tool for Changing Water, Sanitation, and Hygiene Behaviours in Usoma, Kenya. AB - Recent years have witnessed an increase in the use of community based participatory research (CBPR) tools for understanding environment and health issues and facilitating social action. This paper explores the application and utility of photovoice for understanding water, sanitation, and hygiene (WASH) behaviours and catalysing community led solutions to change behaviours. Between June and August 2013, photovoice was conducted with eight (8) women in Usoma, a lakeshore community in Western Kenya with a follow-up community meeting (baraza) in May 2014 to discuss findings with the community members and government officials. In the first part of the study, photovoice one-on-one interviews were used to explore local perceptions and practices around water-health linkages and how the ecological and socio-political environment shapes these perceptions and practices. This paper, which is the second component of the study, uses photovoice group discussions to explore participants' experiences with and (re)action to the photographs and the photovoice project. The findings illustrate that photovoice was an effective CBPR methodology for understanding behaviours, creating awareness, facilitating collective action, and engaging with local government and local health officials at the water-health nexus. PMID- 26380306 TI - GNormPlus: An Integrative Approach for Tagging Genes, Gene Families, and Protein Domains. AB - The automatic recognition of gene names and their associated database identifiers from biomedical text has been widely studied in recent years, as these tasks play an important role in many downstream text-mining applications. Despite significant previous research, only a small number of tools are publicly available and these tools are typically restricted to detecting only mention level gene names or only document level gene identifiers. In this work, we report GNormPlus: an end-to-end and open source system that handles both gene mention and identifier detection. We created a new corpus of 694 PubMed articles to support our development of GNormPlus, containing manual annotations for not only gene names and their identifiers, but also closely related concepts useful for gene name disambiguation, such as gene families and protein domains. GNormPlus integrates several advanced text-mining techniques, including SimConcept for resolving composite gene names. As a result, GNormPlus compares favorably to other state-of-the-art methods when evaluated on two widely used public benchmarking datasets, achieving 86.7% F1-score on the BioCreative II Gene Normalization task dataset and 50.1% F1-score on the BioCreative III Gene Normalization task dataset. The GNormPlus source code and its annotated corpus are freely available, and the results of applying GNormPlus to the entire PubMed are freely accessible through our web-based tool PubTator. PMID- 26380307 TI - Perspectives of Fijian Policymakers on the Obesity Prevention Policy Landscape. AB - In Fiji and other Pacific Island countries, obesity has rapidly increased in the past decade. Therefore, several obesity prevention policies have been developed. Studies show that their development has been hampered by factors within Fiji's policy landscape such as pressure from industry. Since policymakers in the Fijian national government are primarily responsible for the development of obesity policies, it is important to understand their perspectives; we therefore interviewed 15 policymakers from nine Fijian ministries. By applying the "attractor landscape" metaphor from dynamic systems theory, we captured perceived barriers and facilitators in the policy landscape. A poor economic situation, low food self-sufficiency, power inequalities, inappropriate framing of obesity, limited policy evidence, and limited resource sharing hamper obesity policy developments in Fiji. Facilitators include policy entrepreneurs and policy brokers who were active when a window of opportunity opened and who strengthened intersectoral collaboration. Fiji's policy landscape can become more conducive to obesity policies if power inequalities are reduced. In Fiji and other Pacific Island countries, this may be achievable through increased food self-sufficiency, strengthened intersectoral collaboration, and the establishment of an explicit functional focal unit within government to monitor and forecast the health impact of policy changes in non-health sectors. PMID- 26380308 TI - Adherence, Compliance, and Health Risk Factor Changes following Short-Term Physical Activity Interventions. AB - BACKGROUND: Low physical activity (PA) levels are associated with poor health risk factor profiles. Intervention strategies to increase PA and quantify the rate and magnitude of change in risk factors are important. METHODS: Interventions were conducted over 40 days to increase PA in 736 insufficiently active (<150 min/wk PA) participants using either a pedometer or instructor-led group protocol. There were a further 135 active participants as controls. Major cardiovascular and metabolic risk factors, including fitness parameters, were measured before and after intervention. RESULTS: Adherence to the interventions was higher for the group versus pedometer participants (87.1% versus 79.8%) and compliance rates for achieving sufficient levels of PA (>=150 min/wk) were also higher for the group participants (95.8% versus 77.6%). Total weekly PA patterns increased by 300 and 435 minutes, for the pedometer and group participants, respectively. Improvements were found for waist girth, total cholesterol, aerobic fitness, and flexibility relative to controls. The change in vigorous PA, but not moderate PA, was a significant predictor of the change in eight of 11 risk factor variables measured. CONCLUSIONS: Rapid and dramatic increases in PA among previously insufficiently active adults can result in important health benefits. PMID- 26380309 TI - Comparison of Monkeypox Virus Clade Kinetics and Pathology within the Prairie Dog Animal Model Using a Serial Sacrifice Study Design. AB - Monkeypox virus (MPXV) infection of the prairie dog is valuable to studying systemic orthopoxvirus disease. To further characterize differences in MPXV clade pathogenesis, groups of prairie dogs were intranasally infected (8 * 10(3) p.f.u.) with Congo Basin (CB) or West African (WA) MPXV, and 28 tissues were harvested on days 2, 4, 6, 9, 12, 17, and 24 postinfection. Samples were evaluated for the presence of virus and gross and microscopic lesions. Virus was recovered from nasal mucosa, oropharyngeal lymph nodes, and spleen earlier in CB challenged animals (day 4) than WA challenged animals (day 6). For both groups, primary viremia (indicated by viral DNA) was seen on days 6-9 through day 17. CB MPXV spread more rapidly, accumulated to greater levels, and caused greater morbidity in animals compared to WA MPXV. Histopathology and immunohistochemistry (IHC) findings, however, were similar. Two animals that succumbed to disease demonstrated abundant viral antigen in all organs tested, except for brain. Dual IHC staining of select liver and spleen sections showed that apoptotic cells (identified by TUNEL) tended to colocalize with poxvirus antigen. Interestingly splenocytes were labelled positive for apoptosis more often than hepatocytes in both MPXV groups. These findings allow for further characterization of differences between MPXV clade pathogenesis, including identifying sites that are important during early viral replication and cellular response to viral infection. PMID- 26380310 TI - Biological Activities of Tetrodotoxin-Producing Enterococcus faecium AD1 Isolated from Puffer Fishes. AB - Puffer fishes were collected from the central sea in Vietnam from spring to summer season. The eggs were incubated in MRS broth that was used to test the toxicity in mice and isolate the lactic acid bacteria community that could produce tetrodotoxin (TTX). Thin layer chromatography (TLC) and high performance lipid chromatography (HPLC) were used to detect and quantify TTX. As a result, Enterococcus faecium AD1 which was identified by biochemical test and 16S rRNA analysis could produce TTX 0.3 mg/mL when cultured in MRS broth. The bacterium was optimized for TTX production and gave 0.18 mg/mL, 0.07 mg/mL, and 0.15 mg/mL in media prepared from the meat-washing water of freshwater fishes (Pangasius bocourti, Oreochromis sp.) and sea fish (Auxis thazard), respectively, that are also hopeful to answer some poisoning cases related to eating fishes. Enterococcus faecium also showed the wide antimicrobial activities on yeast, Gram negative and -positive bacteria. Extracted exopolysaccharide (EPS) that reacted with 2,2-diphenyl-1-picrylhydrazyl to give IC50 at 5 mg/mL equaled 11 mg/mL ascorbic acid which could show effects on Hela-6 and Hep G2 using sulforhodamine B test. Enterococcus faecium can be claimed as a promising source in tetrodotoxin and biological compounds. PMID- 26380311 TI - Inhibition of Ceramide De Novo Synthesis Ameliorates Diet Induced Skeletal Muscles Insulin Resistance. AB - Nowadays wrong nutritional habits and lack of physical activity give a rich soil for the development of insulin resistance and obesity. Many researches indicate lipids, especially the one from the sphingolipids class, as the group of molecules heavily implicated in the progress of insulin resistance in skeletal muscle. Recently, scientists have focused their scrutiny on myriocin, a potent chemical compound that inhibits ceramide (i.e., central hub of sphingolipids signaling pathway) de novo synthesis. In the present research we evaluated the effects of myriocin application on type 2 diabetes mellitus in three different types of skeletal muscles: (1) slow-oxidative (red gastrocnemius), (2) oxidative glycolytic (soleus), and (3) glycolytic (white gastrocnemius). For these reasons the animals were randomly divided into four groups: "control" (C), "myriocin" (M), "high fat diet" (HFD), "high fat diet" (HFD), and "high fat diet + myriocin" (HFD + M). Our in vivo study demonstrated that ceramide synthesis inhibition reduces intramuscular ceramide, its precursor sphinganine, and its derivatives sphingosine and sphingosine-1-phosphate concentrations. Moreover, FFA and TG contents were also decreased after myriocin treatment. Thus, myriocin presents potential therapeutic perspectives with respect to the treatment of insulin resistance and its serious consequences in obese patients. PMID- 26380312 TI - Urinary Angiotensinogen Could Be a Prognostic Marker of Renoprotective Effects of Alogliptin in Patients with Type 2 Diabetes. AB - BACKGROUND: The aims of this study were (1) to examine the renoprotective effects of alogliptin and (2) to establish urinary angiotensinogen (AGT) as a prognostic marker of renoprotective effects of alogliptin in patients with type 2 diabetes (T2D). METHODS: In 43 patients with T2D (18 women, 66.1 +/- 1.71 years), 25 mg/day of alogliptin was added to the traditional hypoglycemic agents and/or nondrug treatments. Urinary concentrations of albumin (Alb) and AGT, normalized by urinary concentrations of creatinine (Cr) (UAlbCR and UAGTCR, respectively), were measured before and after the 12-week alogliptin treatment. RESULTS: Alogliptin treatment tended to decrease UAlbCR (99.6 +/- 26.8 versus 114.6 +/- 36.0 mg/g Cr, P = 0.198). Based on % change in UAlbCR, patients were divided into two groups, responders (< -25%) and nonresponders (>= -25%), and a logistic analysis of UAGTCR before treatment showed cutoff value of 20.8 ug/g Cr. When all patients were redivided into two groups, those with higher values of UAGTCR before the treatment (Group H, n = 20) and those with lower values (Group L), Group H showed significantly decreased UAlbCR in response to alogliptin (-14.6 +/ 8.6 versus +22.8 +/- 16.8%, P = 0.033). CONCLUSION: Urinary AGT could be a prognostic marker of renoprotective effects of alogliptin in patients with T2D. PMID- 26380313 TI - Serum Calprotectin: A Potential Biomarker for Neonatal Sepsis. AB - INTRODUCTION: The correct diagnosis of neonatal sepsis is a relevant problem because sepsis is one of the most important causes of neonatal morbidity, mortality, and prolonged hospital stay. Calprotectin is an antimicrobial, calcium and zinc binding heterocomplex protein that could be used as a nonspecific marker for activation of granulocytes and mononuclear phagocytes. Calprotectin has been proposed for the diagnosis of inflammatory conditions. Our aim is to study serum calprotectin as a biomarker for neonatal sepsis diagnosis. METHODS: 41 (20 females, 21 males) infants who underwent blood culture due to suspected sepsis were enrolled in the study. Serum calprotectin was measured by a commercial ELISA assay (Calprest, Eurospital, Trieste, Italy). Statistical analysis was performed using the statistical software package Stata 13.1 (Stata Corporation, College Station, Texas, USA). RESULTS: 8 neonates (19.51%) showed sepsis with positive culture and 33 (80.49%) showed suspected sepsis. The optimal cut-off for calprotectin is 2.2 MUg/mL with a sensitivity of 62.5% and a specificity of 69.7%. CONCLUSIONS: Calprotectin may be considered a promising early, sensitive, specific marker of sepsis thanks to the importance of calprotectin in defense mechanisms and physiological functions of the immune system. PMID- 26380314 TI - Mesenchymal Stromal Cell-Derived Factors Promote Tissue Repair in a Small-for Size Ischemic Liver Model but Do Not Protect against Early Effects of Ischemia and Reperfusion Injury. AB - Loss of liver mass and ischemia/reperfusion injury (IRI) are major contributors to postresectional liver failure and small-for-size syndrome. Mesenchymal stromal cell- (MSC-) secreted factors are described to stimulate regeneration after partial hepatectomy. This study investigates if liver-derived MSC-secreted factors also promote liver regeneration after resection in the presence of IRI. C57BL/6 mice underwent IRI of 70% of their liver mass, alone or combined with 50% partial hepatectomy (PH). Mice were treated with MSC-conditioned medium (MSC-CM) or unconditioned medium (UM) and sacrificed after 6 or 24 hours (IRI group) or after 48 hours (IRI + PH group). Blood and liver tissue were analyzed for tissue injury, hepatocyte proliferation, and gene expression. In the IRI alone model, serum ALT and AST levels, hepatic tissue damage, and inflammatory cytokine gene expression showed no significant differences between both treatment groups. In the IRI + PH model, significant reduction in hepatic tissue damage as well as a significant increase in hepatocyte proliferation was observed after MSC-CM treatment. CONCLUSION: Mesenchymal stromal cell-derived factors promote tissue regeneration of small-for-size livers exposed to ischemic conditions but do not protect against early ischemia and reperfusion injury itself. MSC-derived factors therefore represent a promising treatment strategy for small-for-size syndrome and postresectional liver failure. PMID- 26380315 TI - Possible Triggering Effect of Influenza Vaccination on Psoriasis. AB - Psoriasis is a chronic, recurrent, immune-mediated inflammatory disease and it can be provoked or exacerbated by a variety of different environmental factors, particularly infections and drugs. In addition, a possible association between vaccination and the new onset and/or exacerbation of psoriasis has been reported by a number of different authors. The aim of this study is to investigate the effects of influenza vaccination on patients with psoriasis. Here, we report the findings from 43 patients suffering from psoriasis (clinical phenotypes as mixed guttate/plaque lesions, palmoplantar or scalp psoriasis) whose diseases had been triggered after influenza vaccination applied in the 2009-2010 season. The short time intervals between vaccination and psoriasis flares in our patients and the lack of other possible triggers suggest that influenza vaccinations may have provocative effects on psoriasis. However, further large and controlled studies need to be carried out to confirm this relationship. PMID- 26380316 TI - Adsorption of Toll-Like Receptor 4 Agonist to Alum-Based Tetanus Toxoid Vaccine Dampens Pro-T Helper 2 Activities and Enhances Antibody Responses. AB - Aluminum salts gels (alum) are TLR-independent adjuvants and have been used to boost antibody responses in alum-based vaccines such as diphtheria, pertussis, and tetanus toxoid (DPT) triple vaccine. However, the pro-Th2 activity of alum based vaccine formulations has not been fully appreciated. Here we found that alum-based tetanus toxoid (TT) vaccine was biased toward a Th-2 profile as shown by TT-induced airway eosinophilic inflammation, type 2 cytokine production, and high levels of IgE anaphylactic antibodies. The adsorption into alum of prototypic TLR4 agonists such as lipopolysaccharides (LPS) derived from Escherichia coli consistently dampened TT-induced Th2 activities without inducing IFNgamma or Th1-like responses in the lung. Conversely, adsorption of monophosphoryl lipid A (MPLA) extracted from Salmonella minnesota, which is a TIR domain-containing adapter-inducing interferon-beta- (TRIF-) biased TLR4 agonist, was less effective in decreasing Th-2 responses. Importantly, in a situation with antigenic competition (OVA plus TT), TT-specific IgG1 or IgG2a was decreased compared with TT sensitization. Notably, LPS increased the production of IgG1 and IgG2a TT-specific antibodies. In conclusion, the addition of LPS induces a more robust IgG1 and IgG2a TT-specific antibody production and concomitantly decreases Th2-cellular and humoral responses, indicating a potential use of alum/TLR-based vaccines. PMID- 26380318 TI - Targeted Collection of Plasmid DNA in Large and Growing Animal Muscles 6 Weeks after DNA Vaccination with and without Electroporation. AB - DNA vaccination has been developed in the last two decades in human and animal species as a promising alternative to conventional vaccination. It consists in the injection, in the muscle, for example, of plasmid DNA encoding the vaccinating polypeptide. Electroporation which forces the entrance of the plasmid DNA in cells at the injection point has been described as a powerful and promising strategy to enhance DNA vaccine efficacy. Due to the fact that the vaccine is composed of DNA, close attention on the fate of the plasmid DNA upon vaccination has to be taken into account, especially at the injection point. To perform such studies, the muscle injection point has to be precisely recovered and collected several weeks after injection. This is even more difficult for large and growing animals. A technique has been developed to localize precisely and collect efficiently the muscle injection points in growing piglets 6 weeks after DNA vaccination accompanied or not by electroporation. Electroporation did not significantly increase the level of remaining plasmids compared to nonelectroporated piglets, and, in all the cases, the levels were below the limit recommended by the FDA to research integration events of plasmid DNA into the host DNA. PMID- 26380317 TI - Development of Nonaggregating Poly-A Tailed Immunostimulatory A/D Type CpG Oligodeoxynucleotides Applicable for Clinical Use. AB - Immunostimulatory CpG ODNs have been developed and utilized as TLR9-dependent innate immune activators and vaccine adjuvants. Four different types of immunostimulatory CpG ODNs (A/D, B/K, C, and P type) have been reported. A/D type ODNs are characterized by high IFN-alpha production but intrinsically form aggregates, hindering its good manufacturing practice grade preparation. In this study, we developed several D35-derived ODNs (a commonly used A/D type ODN), which were modified with the addition of a phosphorothioate polynucleotide tail (such as dAs40), and examined their physical properties, solubility in saline, immunostimulatory activity on human PBMCs, and vaccine adjuvant potential in monkeys. We found that two modified ODNs including D35-dAs40 and D35core-dAs40 were immunostimulatory, similar to original D35 in human PBMCs, resulting in high IFN-alpha secretion in a dose-dependent manner. Physical property analysis by dynamic light scattering revealed that both D35-dAs40 and D35core-dAs40 did not form aggregates in saline, which is currently impossible for the original D35. Furthermore, D35-dAs40 and D35core-dAs40 worked as better vaccine adjuvant in monkeys. These results suggested that D35-dAs40 and D35core-dAs40 are two promising prototypes of nonaggregating A/D type ODN with advantages of ease of drug preparation for clinical applications as vaccine adjuvants or IFN-alpha inducing immunomodifiers. PMID- 26380319 TI - Non-CpG Oligonucleotides Exert Adjuvant Effects by Enhancing Cognate B Cell-T Cell Interactions, Leading to B Cell Activation, Differentiation, and Isotype Switching. AB - Natural and synthetic nucleic acids are known to exert immunomodulatory properties. Notably, nucleic acids are known to modulate immune function via several different pathways and various cell types, necessitating a complex interpretation of their effects. In this study we set out to compare the effects of a CpG motif containing oligodeoxynucleotide (ODN) with those of a control and an inhibitory non-CpG ODN during cognate B cell-T cell interactions. We employed an antigen presentation system using splenocytes from TCR transgenic DO11.10 mice and the ovalbumin peptide recognized by the TCR as model antigen. We followed early activation events by measuring CD69 expression, late activation by MHC class II expression, cell division and antibody production of switched, and nonswitched isotypes. We found that both of the tested non-CpG ODN exerted significant immunomodulatory effects on early T cell and on late B cell activation events. Importantly, a synergism between non-CpG effects and T cell help acting on B cells was observed, resulting in enhanced IgG production following cognate T cell-B cell interactions. We propose that non-CpG ODN may perform as better adjuvants when a strong antigen-independent immune activation, elicited by CpG ODNs, is undesirable. PMID- 26380320 TI - Differential Immune Response against Recombinant Leishmania donovani Peroxidoxin 1 and Peroxidoxin 2 Proteins in BALB/c Mice. AB - We assessed the immune response against recombinant proteins of two related, albeit functionally different, peroxidoxins from Leishmania donovani: peroxidoxin 1 (LdPxn1) and peroxidoxin 2 (LdPxn2) in BALB/c mice. We also evaluated the effect of coadministration of TLR agonists (CpG ODN and GLA-SE) on the antigen specific immune response. Immunization with recombinant LdPxn1 alone induced a predominantly Th2 type immune response that is associated with the production of high level of IgG1 and no IgG2a isotype while rLdPxn2 resulted in a mixed Th1/Th2 response characterized by the production of antigen-specific IgG2a in addition to IgG1 isotype. Antigen-stimulated spleen cells from mice that were immunized with rLdPxn1 produced low level of IL-10 and IL-4 and no IFN-gamma, whereas cells from mice immunized with rLdPxn2 secreted high level of IFN-gamma, low IL-4, and no IL 10. Coadministration of CpG ODN or GLA-SE with rLdPxn1 skewed the immune response towards a Th 1 type as indicated by robust production of IgG2a isotype. Furthermore, the presence of TLR agonists together with rLdPxn1 antigen enhanced the production of IFN-gamma and to a lesser extent of IL-10. TLR agonists also enhanced a more polarized Th 1 type immune response against rLdPxn2. PMID- 26380321 TI - Are the Two Human Papillomavirus Vaccines Really Similar? A Systematic Review of Available Evidence: Efficacy of the Two Vaccines against HPV. AB - BACKGROUND: When the bivalent and the quadrivalent HPV vaccines were marketed they were presented as having comparable efficacy against cervical cancer. Differences between the vaccines are HPV types included and formulation of the adjuvant. METHOD: A systematic review was conducted to assess the efficacy of the two vaccines against cervical cancer. Outcomes considered were CIN2+, CIN3+, and AIS. RESULTS: Nine reports (38,419 women) were included. At enrollment mean age of women was 20 years, 90% had negative cytology, and 80% were seronegative and/or DNA negative for HPV 16 or 18 (naive women). In the TVC-naive, VE against CIN2+ was 58% (95% CI: 35, 72); heterogeneity was detected, VE being 65% (95% CI: 54, 74) for the bivalent and 43% (95% CI: 23, 57) for the quadrivalent. VE against CIN3+ was 78% (95% CI: <0, 97); heterogeneity was substantial, VE being 93% (95% CI: 77, 98) for the bivalent and 43% (95% CI: 12, 63) for the quadrivalent. VE in the TVC was much lower. No sufficient data were available on AIS. CONCLUSIONS: In naive girls bivalent vaccine shows higher efficacy, even if the number of events detected is low. In women already infected the benefit of the vaccination seems negligible. PMID- 26380322 TI - Innate Immune Memory: The Latest Frontier of Adjuvanticity. AB - Recent findings in the field of immune memory have demonstrated that B and T cell mediated immunity following infections are enhanced by the so-called trained immunity. This effect has been most extensively investigated for the tuberculosis vaccine strain Bacillus Calmette-Guerin (BCG). Epidemiological studies suggest that this vaccine is associated with a substantial reduction in overall child mortality that cannot be solely explained by prevention of the target disease but that it seems to rely on inducing resistance to other infections. Upon infection or vaccination, monocytes/macrophages can be functionally reprogrammed so as to display an enhanced defensive response against unrelated infections. Epigenetic modifications seem to play a key role in the induction of this "innate memory." These findings are revolutionising our knowledge of the immune system, introducing the concept of memory also for mammalian innate immunity. Thus, vaccines are likely to nonspecifically affect the overall immunological status of individuals in a clinically relevant manner. As a consequence, future vaccine strategies ought to take into account the contribution of innate memory through appropriate design of formulations and administration scheduling. PMID- 26380324 TI - Stimulation of Innate and Adaptive Immunity by Using Filamentous Bacteriophage fd Targeted to DEC-205. AB - The filamentous bacteriophage fd, codisplaying antigenic determinants and a single chain antibody fragment directed against the dendritic cell receptor DEC 205, is a promising vaccine candidate for its safety and its ability to elicit innate and adaptive immune response in absence of adjuvants. By using a system vaccinology approach based on RNA-Sequencing (RNA-Seq) analysis, we describe a relevant gene modulation in dendritic cells pulsed with anti-DEC-205 bacteriophages fd. RNA-Seq data analysis indicates that the bacteriophage fd virions are sensed as a pathogen by dendritic cells; they activate the danger receptors that trigger an innate immune response and thus confer a strong adjuvanticity that is needed to obtain a long-lasting adaptive immune response. PMID- 26380323 TI - Local and Systemic IKKepsilon and NF-kappaB Signaling Associated with Sjogren's Syndrome Immunopathogenesis. AB - The activated NF-kappaB signaling pathway plays an important role in pathogenesis of primary Sjogren's syndrome (pSS). The inhibitor of kappaB (IkappaB) kinase (IKK) family such as IKKalpha, IKKbeta, IKKgamma, and IKKepsilon, is required for this signaling. Our aim was to investigate the role of IKKalpha/beta/gamma/epsilon in patients with untreated pSS. In minor salivary glands from pSS patients, phosphorylated IKKepsilon (pIKKepsilon), pIkappaBalpha, and pNF-kappaB p65 (p-p65) were highly expressed in ductal epithelium and infiltrating mononuclear cells by immunohistochemistry, compared to healthy individuals. pIKKalpha/beta and pIKKgamma were both negative. And pIKKepsilon positively related to expression of p-p65. Furthermore, pIKKepsilon and p-p65 expression significantly correlated with biopsy focus score and overall disease activity. Meanwhile, in peripheral blood mononuclear cells from pSS patients, pIKKepsilon, total IKKepsilon, pIKKalpha/beta, and p-p65 were significantly increased by western blot, compared to healthy controls. However, there was no difference in IKKgamma and IkappaBalpha between pSS patients and healthy individuals. These results demonstrated an abnormality of IKKepsilon, IkappaBalpha, and NF-kappaB in pSS, suggesting a potential target of treatment for pSS based on the downregulation of IKKepsilon expression and deregulation of NF-kappaB pathway. PMID- 26380325 TI - Vaccines of the Future: The Role of Inflammation and Adjuvanticity. PMID- 26380327 TI - Application of "Systems Vaccinology" to Evaluate Inflammation and Reactogenicity of Adjuvanted Preventative Vaccines. AB - Advances in "omics" technology (transcriptomics, proteomics, metabolomics, genomics/epigenomics, etc.) allied with statistical and bioinformatics tools are providing insights into basic mechanisms of vaccine and adjuvant efficacy or inflammation/reactogenicity. Predictive biomarkers of relatively frequent inflammatory reactogenicity may be identified in systems vaccinology studies involving tens or hundreds of participants and used to screen new vaccines and adjuvants in in vitro, ex vivo, animal, or human models. The identification of rare events (such as those observed with initial rotavirus vaccine or suspected autoimmune complications) will require interrogation of large data sets and population-based research before application of systems vaccinology. The Innovative Medicine Initiative funded public-private project BIOVACSAFE is an initial attempt to systematically identify biomarkers of relatively common inflammatory events after adjuvanted immunization using human, animal, and population-based models. Discriminatory profiles or biomarkers are being identified, which require validation in large trials involving thousands of participants before they can be generalized. Ultimately, it is to be hoped that the knowledge gained from such initiatives will provide tools to the industry, academia, and regulators to select optimal noninflammatory but immunogenic and effective vaccine adjuvant combinations, thereby shortening product development cycles and identifying unsuitable vaccine candidates that would fail in expensive late stage development or postmarketing. PMID- 26380328 TI - Buprenorphine Prescribing Availability in a Sample of Ohio Specialty Treatment Organizations. AB - OBJECTIVE: Buprenorphine, a medication for treating opioid dependence, is underutilized in specialty addiction treatment organizations. Only physicians who have obtained a buprenorphine prescribing license or "waiver" may administer this medication. A limited number of physicians are pursuing this waiver, and a concern in the substance use disorder treatment field is that the shortage of prescribers could be contributing to the low use of buprenorphine at specialty addiction treatment centers. The objective of this study is to assess Ohio specialty treatment organizations' access to buprenorphine prescribers and the barriers they encounter when seeking new physician prescribing capacity. METHODS: Forty-one Ohio specialty addiction treatment organizations were invited to complete a survey of their buprenorphine practices and availability of buprenorphine prescribers during August-October 2014. Data was collected on pharmacotherapies used in the treatment of opioid dependence, arrangements treatment organizations have with prescribing physicians, buprenorphine prescribing capacity, and barriers encountered in recruiting new physician prescribers. RESULTS: Thirty-seven treatment organizations responded, for a response rate of 90.2%. Seventy-eight percent (n=29) of the sample provided buprenorphine therapy. Of those treatment organizations, 48.3% (n=14) reported insufficient prescribing capacity. Of those, 50% (n=7) indicated they had to turn patients away from buprenorphine therapy due to limited physician prescribing capacity. CONCLUSION: The study suggests that buprenorphine use is constrained by limited physician prescribing capacity, to the degree that 24.1% of the organizations surveyed using buprenorphine therapy had to turn patients away. Potential remedies include encouraging more specialty treatment organizations to have physicians on staff, removing the Drug Addiction Treatment Act (DATA 2000) cap that limits physician buprenorphine caseloads at 100 patients (after year 1), and developing strategies to recruit physicians into addiction treatment practice. Additional research is needed to increase the knowledge of physician prescribing capacity as a barrier to buprenorphine use, how to overcome these barriers, and to understand the extent physician capacity shortages are affecting buprenorphine use. PMID- 26380329 TI - Leadership Styles of Oxford House Officers. AB - Oxford House recovery homes are unusual compared to most recovery homes in that they function entirely without the use of staff; instead members are elected to officer positions. The aim of this study was to perform preliminary analysis of the types of leadership styles utilized by members of oxford house. Twentynine house residents of five Oxford Houses were asked to rate their own leadership styles using the leader behavior description questionnaire and the multifactor leader questionnaire. Results showed that participants were more likely to use person-oriented behaviors above task-oriented actions. Transformational leadership was associated with higher outcomes than Transactional leadership. Implications for future research are discussed. PMID- 26380326 TI - Extracellular Vesicles: Role in Inflammatory Responses and Potential Uses in Vaccination in Cancer and Infectious Diseases. AB - Almost all cells and organisms release membrane structures containing proteins, lipids, and nucleic acids called extracellular vesicles (EVs), which have a wide range of functions concerning intercellular communication and signaling events. Recently, the characterization and understanding of their biological role have become a main research area due to their potential role in vaccination, as biomarkers antigens, early diagnostic tools, and therapeutic applications. Here, we will overview the recent advances and studies of Evs shed by tumor cells, bacteria, parasites, and fungi, focusing on their inflammatory role and their potential use in vaccination and diagnostic of cancer and infectious diseases. PMID- 26380330 TI - Self Portrait With Dr. Arrieta and the Medical Profession's Tenuous Status in the Public Eye. PMID- 26380331 TI - Facklamia Species and Streptococcus pneumoniae Meningitis: A Case Report and Review of the Literature. AB - Facklamia sp are Gram-positive cocci that are often mistaken for viridans streptococci, but they rarely cause invasive disease. In this report, we describe a case of mixed Facklamia sp and Streptococcus pneumoniae meningitis in an immunocompetent host with sinusitis. This case demonstrates that Facklamia sp may be part of normal human flora but can be associated with invasive disease. PMID- 26380332 TI - A Case of Aggregatibacter aphrophilus Multiple Abscess. AB - We report a case of brain and lung abscesses caused by Agreggatibacter aphrophilus in a 43-YEAR-OLD man with past history of splenectomy and drug addiction, in the absence of endocarditis. Microbiological samples remain negatives and diagnosis was made by 16S rDNA PCR performance on abscess fluid for this coccobacillus that belongs to the HACEK group. The patient's clinical symptoms resolved within 6 weeks of treatment with cefotaxim. PMID- 26380333 TI - Adult T-Cell Leukemia/Lymphoma in a Caucasian Patient After Sexual Transmission of Human T-Cell Lymphotropic Virus Type 1. AB - Adult T-cell leukemia/lymphoma (ATLL), a T-cell neoplasm caused by human T-cell lymphotropic virus type 1 (HTLV-1), develops in the majority of cases in individuals who were infected with HTLV-1 as young children, by their mother during prolonged breastfeeding. We report the case of a Caucasian French man, whose parents were HTLV-1-seronegative and who developed ATLL after HTLV-1 sexual transmission by a Cameroonian woman. This hypothesis was corroborated by genotyping of the patient's virus, which revealed an HTLV-1B strain, found only in Central Africa, especially in Cameroon. Thus, ATLL may develop after HTLV-1 infection during adulthood, outside breastfeeding. PMID- 26380334 TI - Fever and Cardiac Arrest in a Patient With a Left Ventricular Assist Device. AB - A 68-year-old avid deer hunter with ischemic cardiomyopathy underwent left ventricular assist device (LVAD) implantation for destination therapy two years ago. He was living an active lifestyle, tracking deer and fishing in a Midwestern forest in November. His wife removed an engorged tick on his thorax. A few days later, he experienced fever, confusion, and ataxia and was hospitalized with septic shock and ventricular fibrillation. The LVAD site had no signs of trauma, drainage, warmth, or tenderness. A peripheral blood smear revealed intraleukocytic anaplasma microcolony inclusions. After completing 14 days of doxycycline, he recovered. Typical non-device-associated infections in LVAD recipients include pneumonia, urinary tract infection, or Clostridium difficile colitis. Human granulocytic anaplasmosis (HGA) is a very atypical non-LVAD infection, and the incidence of tickborne illnesses in LVAD recipients is unknown. PMID- 26380335 TI - Specific Behaviors Predict Staphylococcus aureus Colonization and Skin and Soft Tissue Infections Among Human Immunodeficiency Virus-Infected Persons. AB - Background. Few data exist on the incidence and risk factors of Staphylococcus aureus colonization and skin and soft tissue infections (SSTIs) among patients infected with human immunodeficiency virus (HIV). Methods. Over a 2-year period, we prospectively evaluated adults infected with HIV for incident S aureus colonization at 5 body sites and SSTIs. Cox proportional hazard models using time updated covariates were performed. Results. Three hundred twenty-two participants had a median age of 42 years (interquartile range, 32-49), an HIV duration of 9.4 years (2.7-17.4), and 58% were on highly active antiretroviral therapy (HAART). Overall, 102 patients (32%) became colonized with S aureus with an incidence rate of 20.6 (95% confidence interval [CI], 16.8-25.0) per 100 person-years [PYs]. Predictors of colonization in the final multivariable model included illicit drug use (hazard ratios [HR], 4.26; 95% CI, 1.33-13.69) and public gym use (HR 1.66, 95% CI, 1.04-2.66), whereas antibacterial soap use was protective (HR, 0.50; 95% CI, 0.32-0.78). In a separate model, perigenital colonization was associated with recent syphilis infection (HR, 4.63; 95% CI, 1.01-21.42). Fifteen percent of participants developed an SSTI (incidence rate of 9.4 cases [95% CI, 6.8-12.7] per 100 PYs). Risk factors for an SSTI included incident S aureus colonization (HR 2.52; 95% CI, 1.35-4.69), public shower use (HR, 2.59; 95% CI, 1.48-4.56), and hospitalization (HR 3.54; 95% CI, 1.67-7.53). The perigenital location for S aureus colonization was predictive of SSTIs. Human immunodeficiency virus-related factors (CD4 count, HIV RNA level, and HAART) were not associated with colonization or SSTIs. Conclusions. Specific behaviors, but not HIV-related factors, are predictors of colonization and SSTIs. Behavioral modifications may be the most important strategies in preventing S aureus colonization and SSTIs among persons infected with HIV. PMID- 26380336 TI - The Control of Methicillin-Resistant Staphylococcus aureus Blood Stream Infections in England. AB - Methicillin-resistant Staphylococcus aureus (MRSA) blood stream infection (BSI) is a major healthcare burden in some but not all healthcare settings, and it is associated with 10%-20% mortality. The introduction of mandatory reporting in England of MRSA BSI in 2001 was followed in 2004 by the setting of target reductions for all National Health Service hospitals. The original national target of a 50% reduction in MRSA BSI was considered by many experts to be unattainable, and yet this goal has been far exceeded (~80% reduction with rates still declining). The transformation from endemic to sporadic MRSA BSI involved the implementation of serial national infection prevention directives, and the deployment of expert improvement teams in organizations failed to meet their improvement trajectory targets. We describe and appraise the components of the major public health infection prevention campaign that yielded major reductions in MRSA infection. There are important lessons and opportunities for other healthcare systems where MRSA infection remains endemic. PMID- 26380337 TI - Effect of Intercurrent Infections and Vaccinations on Immune and Inflammatory Biomarkers Among Human Immunodeficiency Virus-Infected Adults on Suppressive Antiretroviral Therapy. AB - We used generalized estimating equations to quantify the impact of recent vaccination or intercurrent infections on immune and inflammatory biomarkers among 144 human immunodeficiency virus (HIV)-infected adults with HIV RNA < 50 copies/mL on antiretroviral therapy. These events were associated with a 2.244 ug/mL increase in high sensitivity C-reactive protein and should be routinely assessed in future studies. PMID- 26380338 TI - Does Iron Increase the Risk of Malaria in Pregnancy? AB - Background. Pregnancy-associated malaria (PAM) remains a significant health concern in sub-Saharan Africa. Cross-sectional studies report that iron might be associated with increased malaria morbidity, raising fears that current iron supplementation policies will cause harm in the present context of increasing resistance against intermittent preventive treatment in pregnancy (IPTp). Therefore, it is necessary to assess the relation of iron levels with malaria risk during the entire pregnancy. Methods. To investigate the association of maternal iron levels on malaria risk in the context of an IPTp clinical trial, 1005 human immunodeficiency virus-negative, pregnant Beninese women were monitored throughout their pregnancy between January 2010 and May 2011. Multilevel models with random intercept at the individual levels and random slope for gestational age were used to analyze the factors associated with increased risk of a positive blood smear and increased Plasmodium falciparum density. Results. During the follow-up, 29% of the women had at least 1 episode of malaria. On average, women had 0.52 positive smears (95% confidence interval [CI], 0.44-0.60). High iron levels (measured by the log10 of ferritin corrected on inflammation) were significantly associated with increased risk of a positive blood smear (adjusted odds ratio = 1.75; 95% CI, 1.46-2.11; P < .001) and high P falciparum density (beta estimate = 0.22; 95% CI, 0.18-0.27; P < .001) during the follow-up period adjusted on pregnancy parameters, comorbidities, environmental and socioeconomic indicators, and IPTp regime. Furthermore, iron-deficient women were significantly less likely to have a positive blood smear and high P falciparum density (P < .001 in both cases). Conclusions. Iron levels were positively associated with increased PAM during pregnancy in the context of IPTp. Supplementary interventional studies are needed to determine the benefits and risks of differently dosed iron and folate supplements in malaria-endemic regions. PMID- 26380339 TI - A Human Immunodeficiency Virus Controller With a Large Population of CD4(+)CD8(+) Double-Positive T Cells. AB - Human immunodeficiency virus (HIV) controllers are patients who control viral replication without antiretroviral therapy. We present the case of an HIV controller who had CD4 and CD8 coexpressed on 40% of his T cells. Although a recent study found that double-positive T cells had superior antiviral capacity in HIV-1 controllers, in this case, the CD4(+)CD8(+) T cells did not have strong antiviral activity. PMID- 26380340 TI - Safety and Immunogenicity of Modified Vaccinia Ankara-Bavarian Nordic Smallpox Vaccine in Vaccinia-Naive and Experienced Human Immunodeficiency Virus-Infected Individuals: An Open-Label, Controlled Clinical Phase II Trial. AB - Background. First- and second-generation smallpox vaccines are contraindicated in individuals infected with human immunodeficiency virus (HIV). A new smallpox vaccine is needed to protect this population in the context of biodefense preparedness. The focus of this study was to compare the safety and immunogenicity of a replication-deficient, highly attenuated smallpox vaccine modified vaccinia Ankara (MVA) in HIV-infected and healthy subjects. Methods. An open-label, controlled Phase II trial was conducted at 36 centers in the United States and Puerto Rico for HIV-infected and healthy subjects. Subjects received 2 doses of MVA administered 4 weeks apart. Safety was evaluated by assessment of adverse events, focused physical exams, electrocardiogram recordings, and safety laboratories. Immune responses were assessed using enzyme-linked immunosorbent assay (ELISA) and a plaque reduction neutralization test (PRNT). Results. Five hundred seventy-nine subjects were vaccinated at least once and had data available for analysis. Rates of ELISA seropositivity were comparably high in vaccinia-naive healthy and HIV-infected subjects, whereas PRNT seropositivity rates were higher in healthy compared with HIV-infected subjects. Modified vaccinia Ankara was safe and well tolerated with no adverse impact on viral load or CD4 counts. There were no cases of myo-/pericarditis reported. Conclusions. Modified vaccinia Ankara was safe and immunogenic in subjects infected with HIV and represents a promising smallpox vaccine candidate for use in immunocompromised populations. PMID- 26380341 TI - An Audit-Based, Infectious Disease Specialist-Guided Antimicrobial Stewardship Program Profoundly Reduced Antibiotic Use Without Negatively Affecting Patient Outcomes. AB - Background. Antimicrobial stewardship programs are increasingly implemented in hospital care. They aim to simultaneously optimize outcomes for individual patients with infections and reduce financial and health-associated costs of overuse of antibiotics. Few studies have examined the effects of antimicrobial stewardship programs in settings with low proportions of antimicrobial resistance, such as in Sweden. Methods. An antimicrobial stewardship program was introduced during 5 months of 2013 in a department of internal medicine in southern Sweden. The intervention consisted of audits twice weekly on all patients given antibiotic treatment. The intervention period was compared with a historical control consisting of patients treated with antibiotics in the same wards in 2012. Studied outcome variables included 28-day mortality and readmission, length of hospital stay, and use of antibiotics. Results. A reduction of 27% in total antibiotic use (2387 days of any antibiotic) was observed in the intervention period compared with the control period. The reduction was due to fewer patients started on antibiotics as well as to significantly shorter durations of antibiotic courses (P < .001). An earlier switch to oral therapy and a specific reduction in use of third-generation cephalosporins and fluoroquinolones was also evident. Mortality, total readmissions, and lengths of stay in hospital were unchanged compared with the control period, whereas readmissions due to a nonresolved infection were fewer during the intervention of 2013. Conclusions. This study demonstrates that an infectious disease specialist-guided antimicrobial stewardship program can profoundly reduce antibiotic use in a low-resistance setting with no negative effect on patient outcome. PMID- 26380342 TI - Antibody-Dependent Cellular Inhibition Is Associated With Reduced Risk Against Febrile Malaria in a Longitudinal Cohort Study Involving Ghanaian Children. AB - The antibody-dependent respiratory burst and opsonic phagocytosis assays have been associated with protection against malaria; however, other mechanisms may also be involved. The antibody-dependent cellular inhibition (ADCI) assay is yet to be correlated with protection in longitudinal cohort studies (LCS). We investigated the relationship between ADCI activity of immunoglobulin G before malaria season and risk of malaria in a LCS involving Ghanaian children. High ADCI activity was significantly associated with reduced risk against malaria. Findings here suggest a potential usefulness of the ADCI assay as a correlate of protection to guide malaria vaccine studies. PMID- 26380343 TI - Transcriptional Changes in CD8(+) T Cells During Antiretroviral Therapy Intensified With Raltegravir. AB - Background. Intensification of antiretroviral therapy with raltegravir does not affect levels of residual human immunodeficiency virus (HIV)-1 viremia, but it has led to increased levels of episomal HIV-1 DNA in some patients, suggesting antiviral activity against otherwise unresponsive components of the viral reservoir. Effects of raltegravir on host cells remain less well understood. Methods. We used comprehensive and unbiased microarray-based transcriptional profiling to analyze gene expression changes in CD8(+) T cells from participants in a randomized clinical trial (AIDS Clinical Trials Group [ACTG] A5244) comparing raltegravir-intensified to nonintensified antiretroviral therapy. Results. Although raltegravir intensification failed to induce statistically significant changes in HIV-1 DNA or residual plasma viremia, we observed significant increases in the expression intensity of 121 host gene transcripts. In functional annotations of these transcripts, we found that they were mainly involved in glucose and carbohydrate metabolism, immune regulation, control of cell proliferation, and tumor suppression. Two of the raltegravir-responsive gene transcripts were statistically correlated with levels of residual HIV-1 RNA, but none of the remaining 119 transcripts were associated with immunologic or virologic characteristics of the study patients. Conclusions. Together, these findings demonstrate that raltegravir intensification can induce previously unrecognized, statistically significant gene expression changes in host CD8(+) T lymphocytes. PMID- 26380344 TI - Preexisting Immunity, More Than Aging, Influences Influenza Vaccine Responses. AB - Background. Influenza disproportionately impacts older adults while current vaccines have reduced effectiveness in the older population. Methods. We conducted a comprehensive evaluation of cellular and humoral immune responses of adults aged 50 years and older to the 2008-2009 seasonal trivalent inactivated influenza vaccine and assessed factors influencing vaccine response. Results. Vaccination increased hemagglutination inhibition and neutralizing antibody; however, 66.3% of subjects did not reach hemagglutination inhibition titers >= 40 for H1N1, compared with 22.5% for H3N2. Increasing age had a minor negative impact on antibody responses, whereas prevaccination titers were the best predictors of postvaccination antibody levels. Preexisting memory B cells declined with age, especially for H3N2. However, older adults still demonstrated a significant increase in antigen-specific IgG(+) and IgA(+) memory B cells postvaccination. Despite reduced frequency of preexisting memory B cells associated with advanced age, fold-rise in memory B cell frequency in subjects 60+ was comparable to subjects age 50-59. Conclusions. Older adults mounted statistically significant humoral and cell-mediated immune responses, but many failed to reach hemagglutination inhibition titers >=40, especially for H1N1. Although age had a modest negative effect on vaccine responses, prevaccination titers were the best predictor of postvaccination antibody levels, irrespective of age. PMID- 26380346 TI - Disseminated Mycobacterial Infection After International Medical Tourism. AB - International travel for the purpose of receiving medical care is increasing. We report a case of disseminated mycobacterial infection after fetal stem cell infusion. PMID- 26380345 TI - Corynebacterium pseudotuberculosis Pneumonia in a Veterinary Student Infected During Laboratory Work. AB - We present a case of Corynebacterium pseudotuberculosis pneumonia in a veterinary student, with molecular genetic evidence of acquisition during laboratory work, an observation relevant for laboratory personnel working with C pseudotuberculosis isolates. The patient was clinically cured with 14 months trimethoprim/sulfamethoxazole and rifampicin combination treatment. PMID- 26380347 TI - Histoplasmosis-Induced Hemophagocytic Syndrome: A Case Series and Review of the Literature. AB - Background. Histoplasmosis-associated hemophagocytic lymphohistiocytosis (HLH) is a relatively rare disorder for which data are limited regarding optimal treatment and clinical outcomes in adults. We describe the clinical features, treatment, and outcomes of patients with histoplasmosis-associated HLH at our institution. Methods. We performed a retrospective chart review of all inpatients at Parkland Hospital diagnosed with HLH associated with Histoplasma capsulatum from 2003 to 2013. Results. Eleven cases of histoplasmosis-associated HLH over this time period were identified. Nine of eleven cases were males (82%). Nine of these patients had human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS), 1 was a renal transplant patient on immunosuppressants, and the other had no documented immunocompromise. The most common HLH criteria were splenomegaly (n = 10), fever (n = 10), and ferritin >500 ng/dL (n = 9). Urine Histoplasma antigen was positive in every patient tested (n = 9 of 9), and most antibodies for Histoplasma were positive if checked (n = 4 of 5). A majority of patients received liposomal amphotericin B (n = 9) with an average treatment duration of 11 days, and 5 patients also received prednisone, intravenous immunoglobulin (IVIG), or both. Overall, 5 patients died within 30 days (45.5%), and 7 patients died within 90 days (63.6%). Of the 5 patients that received immunosuppression, 4 died (80%), whereas in the group not given additional immunosuppression (n = 5), 2 died (40%). Conclusions. Histoplasmosis associated HLH among adults is a lethal disease of highly immunocompromised patients, especially patients with HIV/AIDS. Clinical features such as splenomegaly, elevated ferritin, and cytopenias should prompt evaluation for HLH in this population. Further data are needed to define the role of immunosuppression, IVIG, and highly active antiretroviral therapy in treating this condition. PMID- 26380349 TI - ERRATUM. AB - [This corrects the article DOI: 10.1093/ofid/ofu046.]. PMID- 26380348 TI - Analysis of Subgroup Differences in the ION-3 Trial of Ledipasvir-Sofosbuvir in Chronic Hepatitis C Infection. PMID- 26380350 TI - Switch to Raltegravir From Protease Inhibitor or Nonnucleoside Reverse Transcriptase Inhibitor Does not Reduce Visceral Fat In Human Immunodeficiency Virus-Infected Women With Central Adiposity. AB - Human immunodeficiency virus-infected women with central adiposity switched to raltegravir-based antiretroviral therapy immediately or after 24 weeks. No statistically significant changes in computed tomography-quantified visceral adipose tissue (VAT) or subcutaneous fat were observed, although 48 weeks of raltegravir was associated with a 6.4% VAT decline. Raltegravir for 24 weeks was associated with improvements in lipids. PMID- 26380351 TI - Changes in Clinical Presentation and Epidemiology of Respiratory Pathogens Associated With Acute Respiratory Illness in Military Trainees After Reintroduction of Adenovirus Vaccine. AB - Background. Adenovirus (Ad) has long been the predominant cause of acute respiratory illness (ARI) in military trainees. In 2011, live oral Ad vaccines for serotypes 4 and 7 were reintroduced into US basic military training populations. This study evaluated the impact on clinical presentations and other respiratory pathogens. Methods. The Center for Advanced Molecular Detection at Joint Base San Antonio-Lackland prospectively collects demographic, clinical, and polymerase chain reaction data from respiratory specimens (throat swab and nasal wash) among Air Force trainees presenting for care of ARI. Results. From June 2008 to August 2013, 2660 trainees enrolled and were tested for selected respiratory pathogens. Post-vaccine introduction (VI), reported systemic symptoms were less frequent, including fever (38% vs 94%) and myalgia (37% vs 67%; P < .01). Median temperature and heart rate decreased (98.4 vs 101.3 degrees F, 81 vs 96 beats per minute; P < .01). Ad detection decreased for all Ad (3% vs 68%), Ad4 (1% vs 70%), 7 (0% vs 8%), 14 (0% vs 5%), and 3 (0.1% vs 2%); P < .01). Rhinovirus and cases with no pathogen identified increased in frequency (35% vs 18%, 51% vs 14%; P < .01). Conclusions. Acute respiratory illness in military trainees post-VI is associated with decreased severity of systemic symptoms and reduced fever and heart rate. Marked reductions in frequency of Ad serotypes are seen, including those in the vaccine, with no serotype shift. However, detection of several other respiratory pathogens, most notably rhinovirus, is observed in increasing proportions, and a majority are now undiagnosed clinical syndromes. PMID- 26380352 TI - I Want Your Sex: The Role of Sexual Exploration in Fostering Positive Sexual Self Concepts for Heterosexual and Sexual Minority Women. AB - Openness and self-exploration have been associated with myriad benefits. Within the realm of sexuality, sexual exploration may be 1 facet of openness and self exploration that yields benefits. Prior literature suggests that such exploration may have benefits for sexual orientation minority persons, though limited research has investigated the benefits of sexual exploration for heterosexuals. The present study used data from 346 adult women (185 exclusively heterosexual, 161 not exclusively heterosexual) to investigate the role of sexual exploration as a mediator between sexual orientation status and positivity toward sex. Results of a structural equation modeling analysis supported mediation of the relationship between sexual orientation and sexual positivity via sexual exploration. Implications for future research and clinical interventions are presented. PMID- 26380353 TI - Immunologic monitoring during a phase 2a trial of the GNbAC1 antibody in patients with MS. AB - OBJECTIVE: To monitor the systemic immune responses of patients with multiple sclerosis (MS) under treatment with GNbAC1, a monoclonal antibody against the envelope protein of the MS- associated retrovirus, during a phase 2a trial. METHODS: We analyzed the composition of immune cell subsets and the activation level of monocytes by flow cytometry and the response against viral and vaccine antigens by ELISpot. RESULTS: None of the endpoints measured revealed any immunosuppressive effect of the therapeutic antibody. Activation of monocytes slightly decreased during treatment as predicted by the hypothesized mechanism of action of GNbAC1. CONCLUSION: These results support the conclusion that the antibody is safe for use in patients with MS. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that in patients with MS GNbAC1 does not significantly affect several biomarkers of systemic immune response. PMID- 26380354 TI - Deregulated Fcgamma receptor expression in patients with CIDP. AB - OBJECTIVE: To evaluate the expression of activating and inhibitory Fc-gamma receptors (FcgammaRs) before and during clinically effective therapy with IV immunoglobulin (IVIg) in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). METHODS: Peripheral blood leukocyte subsets, including classical CD14(high)CD16(-) and nonclassical inflammatory CD14(low)CD16(+) monocytes as well as naive CD19(+)CD27(-) and memory CD19(+)CD27(+) B cells, were obtained at baseline and monitored at 2 and 4-8 weeks after initiation of IVIg therapy. RESULTS: Compared with healthy donors matched by age and sex, patients with CIDP showed increased expression levels of the activating high-affinity FcgammaR1 on CD14(high)CD16(-) (p < 0.001) and CD14(low)CD16(+) monocytes (p < 0.001). Expression of the activating low-affinity FcgammaRIIA was increased on CD14(low)CD16(+) monocytes (p = 0.023). Conversely, expression of the inhibitory FcgammaRIIB was reduced on naive (p = 0.009) and memory (p = 0.002) B cells as well as on CD14(high)CD16(-) monocytes (p = 0.046). Clinically effective IVIg therapy partially restored deregulated FcgammaR expression on B cell subsets and monocytes. CONCLUSIONS: The FcgammaR regulatory system is disturbed in patients with CIDP. Balancing activating vs inhibitory FcgammaR expression might provide a clinical benefit for patients with CIDP. PMID- 26380355 TI - The Pathogenesis and Treatment of Emotion Dysregulation in Borderline Personality Disorder. AB - Uncontrollable emotional lability and impulsivity are a paramount phenomenon of Borderline Personality Disorder (BPD). This paper aims to review theories that entertain emotion dysregulation as the core deficit of BPD and a key factor in the etiology of BPD, in order, then, to propose the author's own theory, which arguably transcends certain limitations of the earlier ones. The author asserts that his psychodynamic theory explains the symptoms of BPD more thoroughly and it inspires a more parsimonious interpretation of brain imaging findings. In closing, the author draws implications of the proposed theory for clinical practice. He reports an efficacy study for treatment of emotion dysregulation based on that theory. PMID- 26380356 TI - Exploring Environment-Intervention Fit: A Study of a Work Environment Intervention Program for the Care Sector. AB - Targeting occupational health and safety interventions to different groups of employees and sectors is important. The aim of this study was to explore the environment-intervention fit of a Danish psychosocial work environment intervention program for the residential and home care sector. Focus group interviews with employees and interviews with mangers were conducted at 12 selected workplaces and a questionnaire survey was conducted with managers at all 115 workplaces. The interventions enhanced the probability of employees experiencing more "good" work days, where they could make a difference to the lives of clients. The interventions may therefore be characterized as culturally compelling and having a good fit with the immediate work environment of employees. The interventions furthermore seemed to fit well with the wider organizational environment and with recent changes in the societal and economic context of workplaces. However, some workplaces had difficulties with involving all employees and adapting the interventions to the organization of work. The findings suggest that flexibility and a variety of strategies to involve all employees are important aspects, if interventions are to fit well with the care sector. The focus on employees' conceptualization of a "good" work day may be useful for intervention research in other sectors. PMID- 26380357 TI - A Modern Syllogistic Method in Intuitionistic Fuzzy Logic with Realistic Tautology. AB - The Modern Syllogistic Method (MSM) of propositional logic ferrets out from a set of premises all that can be concluded from it in the most compact form. The MSM combines the premises into a single function equated to 1 and then produces the complete product of this function. Two fuzzy versions of MSM are developed in Ordinary Fuzzy Logic (OFL) and in Intuitionistic Fuzzy Logic (IFL) with these logics augmented by the concept of Realistic Fuzzy Tautology (RFT) which is a variable whose truth exceeds 0.5. The paper formally proves each of the steps needed in the conversion of the ordinary MSM into a fuzzy one. The proofs rely mainly on the successful replacement of logic 1 (or ordinary tautology) by an RFT. An improved version of Blake-Tison algorithm for generating the complete product of a logical function is also presented and shown to be applicable to both crisp and fuzzy versions of the MSM. The fuzzy MSM methodology is illustrated by three specific examples, which delineate differences with the crisp MSM, address the question of validity values of consequences, tackle the problem of inconsistency when it arises, and demonstrate the utility of the concept of Realistic Fuzzy Tautology. PMID- 26380358 TI - Tailoring Healthy Workplace Interventions to Local Healthcare Settings: A Complexity Theory-Informed Workplace of Well-Being Framework. AB - Many healthy workplace interventions have been developed for healthcare settings to address the consistently low scores of healthcare professionals on assessments of mental and physical well-being. Complex healthcare settings present challenges for the scale-up and spread of successful interventions from one setting to another. Despite general agreement regarding the importance of the local setting in affecting intervention success across different settings, there is no consensus on what it is about a local setting that needs to be taken into account to design healthy workplace interventions appropriate for different local settings. Complexity theory principles were used to understand a workplace as a complex adaptive system and to create a framework of eight domains (system characteristics) that affect the emergence of system-level behaviour. This Workplace of Well-being (WoW) framework is responsive and adaptive to local settings and allows a shared understanding of the enablers and barriers to behaviour change by capturing local information for each of the eight domains. We use the results of applying the WoW framework to one workplace, a UK National Health Service ward, to describe the utility of this approach in informing design of setting-appropriate healthy workplace interventions that create workplaces conducive to healthy behaviour change. PMID- 26380359 TI - One-Year Follow-Up of the Effectiveness of Cognitive Behavioral Group Therapy for Patients' Depression: A Randomized, Single-Blinded, Controlled Study. AB - The aim of the study was to investigate the long-term (one year) effectiveness of a 12-session weekly cognitive behavior group therapy (CBGT) on patients with depression. This was a single-blind randomized controlled study with a 2-arm parallel group design. Eighty-one subjects were randomly assigned to 12 sessions intervention group (CBGT) or control group (usual outpatient psychiatric care group) and 62 completed the study. The primary outcome was depression measured with Beck Depression Inventory (BDI-II) and Hamilton Rating Scale for Depression (HRSD). The secondary outcomes were automatic thoughts measured by automatic thoughts questionnaire (ATQ). Both groups were evaluated at the pretest (before 2 weeks), posttest (after 12 therapy sessions), and short- (3 months), medium- (6 months), and long-term (12 months) follow-up. After receiving CBGT, the experimental group had a statistically significant reduction in the BDI-II from 40.30 at baseline to 17.82 points at session eight and to 10.17 points at postintervention (P < 0.001). Similar effects were seen on the HRSD. ATQ significantly decreased at the 12th session, 6 months after sessions, and 1 year after the sessions ended (P < 0.001). We concluded that CBGT is effective for reducing depression and continued to be effective at 1 year of follow-up. PMID- 26380360 TI - Considering the Differential Impact of Three Facets of Organizational Health Climate on Employees' Well-Being. AB - One potential way that healthy organizations can impact employee health is by promoting a climate for health within the organization. Using a definition of health climate that includes support for health from multiple levels within the organization, this study examines whether all three facets of health climate--the workgroup, supervisor, and organization--work together to contribute to employee well-being. Two samples are used in this study to examine health climate at the individual level and group level in order to provide a clearer picture of the impact of the three health climate facets. k-means cluster analysis was used on each sample to determine groups of individuals based on their levels of the three health climate facets. A discriminant function analysis was then run on each sample to determine if clusters differed on a function of employee well-being variables. Results provide evidence that having strength in all three of the facets is the most beneficial in terms of employee well-being at work. Findings from this study suggest that organizations must consider how health is treated within workgroups, how supervisors support employee health, and what the organization does to support employee health when promoting employee health. PMID- 26380361 TI - When Intervention Meets Organisation, a Qualitative Study of Motivation and Barriers to Physical Exercise at the Workplace. AB - OBJECTIVE: To provide a comprehensive understanding of the motivational factors and barriers that are important for compliance with high-intensity workplace physical exercise that is aimed at reducing musculoskeletal disorders. METHOD: The present study, which used semideductive, thematic, and structured in-depth interviews, was nested in a 20-week cluster randomised controlled trial among office workers. Interviews were conducted with 18 informants with diverse fields of sedentary office work who participated in strength training at the workplace for 20 minutes, three times per week. Organisational, implementational, and individual motives and barriers were explored. RESULTS & DISCUSSION: The results show that attention should be given to the interaction between the management, the employees, and the intervention, as the main barrier to compliance was the internal working culture. The results emphasised the need for a clear connection between the management's implementational intentions and the actual implementation. The results emphasise the importance of ensuring the legitimacy of the intervention among managers, participants, and colleagues. Moreover, it is important to centrally organise, structure, and ensure flexibility in the working day to free time for participants to attend the intervention. Recommendations from this study suggest that a thorough intervention mapping process should be performed to analyse organisational and implementational factors before initiating workplace physical exercise training. PMID- 26380362 TI - Workplace Health Promotion and Wellbeing. PMID- 26380363 TI - Probability and Statistics with Applications in Finance and Economics. PMID- 26380364 TI - Universal Keyword Classifier on Public Key Based Encrypted Multikeyword Fuzzy Search in Public Cloud. AB - Cloud computing has pioneered the emerging world by manifesting itself as a service through internet and facilitates third party infrastructure and applications. While customers have no visibility on how their data is stored on service provider's premises, it offers greater benefits in lowering infrastructure costs and delivering more flexibility and simplicity in managing private data. The opportunity to use cloud services on pay-per-use basis provides comfort for private data owners in managing costs and data. With the pervasive usage of internet, the focus has now shifted towards effective data utilization on the cloud without compromising security concerns. In the pursuit of increasing data utilization on public cloud storage, the key is to make effective data access through several fuzzy searching techniques. In this paper, we have discussed the existing fuzzy searching techniques and focused on reducing the searching time on the cloud storage server for effective data utilization. Our proposed Asymmetric Classifier Multikeyword Fuzzy Search method provides classifier search server that creates universal keyword classifier for the multiple keyword request which greatly reduces the searching time by learning the search path pattern for all the keywords in the fuzzy keyword set. The objective of using BTree fuzzy searchable index is to resolve typos and representation inconsistencies and also to facilitate effective data utilization. PMID- 26380365 TI - Game Theory Based Trust Model for Cloud Environment. AB - The aim of this work is to propose a method to establish trust at bootload level in cloud computing environment. This work proposes a game theoretic based approach for achieving trust at bootload level of both resources and users perception. Nash equilibrium (NE) enhances the trust evaluation of the first-time users and providers. It also restricts the service providers and the users to violate service level agreement (SLA). Significantly, the problem of cold start and whitewashing issues are addressed by the proposed method. In addition appropriate mapping of cloud user's application to cloud service provider for segregating trust level is achieved as a part of mapping. Thus, time complexity and space complexity are handled efficiently. Experiments were carried out to compare and contrast the performance of the conventional methods and the proposed method. Several metrics like execution time, accuracy, error identification, and undecidability of the resources were considered. PMID- 26380366 TI - Evaluation of the Effectiveness of a Psychoeducational Intervention in Treatment Naive Patients with Antidepressant Medication in Primary Care: A Randomized Controlled Trial. AB - BACKGROUND: There is evidence supporting the effectiveness of psychoeducation (PE) in patients with symptoms of depression in primary care (PC), but very few studies have assessed this intervention in antidepressant-naive patients. The aim of this study is to assess the effectiveness of a PE program in these patients, since the use of antidepressant (AD) medication may interfere with the effects of the intervention. METHODS: 106 participants were included, 50 from the PE program (12 weekly 1.5-hour sessions) and 56 from the control group (CG) that received the usual care. Patients were assessed at baseline and at 3, 6, and 9 months. The main outcome measures were the Beck Depression Inventory (BDI) and remission based on the BDI. The analysis was carried out on an intention-to-treat basis. RESULTS: The PE program group showed remission of symptoms of 40% (P = 0.001) posttreatment and 42% (P = 0.012) at 6 months. The analysis only showed significant differences in the BDI score posttreatment (P = 0.008; effect size Cohen's d' = 0.55). CONCLUSIONS: The PE intervention is an effective treatment in the depressive population not treated with AD medication. Before taking an AD, psychoeducational intervention should be considered. PMID- 26380367 TI - Social Anxiety among Chinese People. AB - The experience of social anxiety has largely been investigated among Western populations; much less is known about social anxiety in other cultures. Unlike the Western culture, the Chinese emphasize interdependence and harmony with social others. In addition, it is unclear if Western constructed instruments adequately capture culturally conditioned conceptualizations and manifestations of social anxiety that might be specific to the Chinese. The present study employed a sequence of qualitative and quantitative approaches to examine the assessment of social anxiety among the Chinese people. Interviews and focus group discussions with Chinese participants revealed that some items containing the experience of social anxiety among the Chinese are not present in existing Western measures. Factor analysis was employed to examine the factor structure of the more comprehensive scale. This approach revealed an "other concerned anxiety" factor that appears to be specific to the Chinese. Subsequent analysis found that the new factor-other concerned anxiety-functioned the same as other social anxiety factors in their association with risk factors of social anxiety, such as attachment, parenting, behavioral inhibition/activation, and attitude toward group. The implications of these findings for a more culturally sensitive assessment tool of social anxiety among the Chinese were discussed. PMID- 26380368 TI - The State of the Art of the DSM-5 "with Mixed Features" Specifier. AB - The new DSM-5 "with mixed features" specifier (MFS) has renewed the interest of the scientific community in mixed states, leading not only to new clinical studies but also to new criticisms of the current nosology. Consequently, in our paper we have reviewed the latest literature, trying to understand the reactions of psychiatrists to the new nosology and its epidemiological, prognostic, and clinical consequences. It seems that the most widespread major criticism is the exclusion from the DSM-5 MFS of overlapping symptoms (such as psychomotor agitation, irritability, and distractibility), with a consequent reduction in diagnostic power. On the other hand, undoubtedly the new DSM-5 classification has helped to identify more patients suffering from a mixed state by broadening the narrow DSM-IV-TR criteria. As for the clinical presentation, the epidemiological data, and the therapeutic outcomes, the latest literature does not point out a univocal point of view and further research is needed to fully assess the implications of the new DSM-5 MFS. It is our view that a diagnostic category should be preferred to a specifier and mixed states should be better considered as a spectrum of states, according to what was stated many years ago by Kraepelin. PMID- 26380369 TI - Temperature Effect on Exploitation and Interference Competition among Microcystis aeruginosa, Planktothrix agardhii and, Cyclotella meneghiniana. AB - We studied the effect of temperature (18 and 30 degrees C) on growth and on the exploitation and interference competition of three species: Microcystis aeruginosa (MIJAC), Planktothrix agardhii (PAT), and Cyclotella meneghiniana (CCAP). Coculturing the organisms in batch systems allowed for the examination of both competitive interactions, while the interference competition was studied in cross-cultures. The experiments were done during 10-12 days, and samples were taken for chlorophyll-a analysis, using PHYTO-PAM. The temperature did not influence exploitation competition between MIJAC and other competitors and it was the best competitor in both temperatures. PAT presented higher growth rates than CCAP in competition at 18 and 30 degrees C. The temperature influenced the interference competition. The growth of MIJAC was favored in strains exudates at 30 degrees C, while CCAP was favored at 18 degrees C, revealing that the optimum growth temperature was important to establish the competitive superiority. Therefore, we can propose two hypotheses: (i) different temperatures may results in production of distinct compounds that influence the competition among phytoplankton species and (ii) the target species may have different vulnerability to these compounds depending on the temperature. At last, we suggest that both the sensitivity and the physiological status of competing species can determine their lasting coexistence. PMID- 26380370 TI - Supervisors' Strategies to Facilitate Work Functioning among Employees with Musculoskeletal Complaints: A Focus Group Study. AB - AIM: To explore what strategies the supervisors found beneficial to prevent or reduce sickness absence among employees with musculoskeletal complaints. METHODS: Five focus groups were conducted and 26 supervisors from health and social sector participated. Commonly used strategies to prevent sickness absence and interdisciplinary cooperation in this work were discussed in the focus groups. Systematic text condensation was used to analyse the data. RESULTS: The supervisors described five strategies for sick leave management: (1) promoting well-being and a healthy working environment, (2) providing early support and adjustments, (3) making employees more responsible, (4) using confrontational strategies in relation to employees on long-term sick leave, and (5) cooperation with general practitioners (GPs). CONCLUSIONS: Strategies of promoting a healthy working environment and facilitating early return to work were utilised in the follow-up of employees with musculoskeletal complaints. Supportive strategies were found most useful especially in the early phases, while finding a balance between being supportive, on one side, and confronting the employee, on the other, was endeavoured in cases of recurrent or long-term sick leave. Further, the supervisors requested a closer cooperation with the GPs, which they believed would facilitate return to work. PMID- 26380371 TI - Shear Bond Strength of Orthodontic Brackets Fixed with Remineralizing Adhesive Systems after Simulating One Year of Orthodontic Treatment. AB - The objective of this study is to assess, in vitro, the shear bond strength of orthodontic brackets fixed with remineralizing adhesive systems submitted to thermomechanical cycling, simulating one year of orthodontic treatment. Sixty four bovine incisor teeth were randomly divided into 4 experimental groups (n = 16): XT: Transbond XT, QC: Quick Cure, OL: Ortholite Color, and SEP: Transbond Plus Self-Etching Primer. The samples were submitted to thermomechanical cycling simulating one year of orthodontic treatment. Shear bond strength tests were carried out using a universal testing machine with a load cell of 50 KgF at 0.5 mm/minute. The samples were examined with a stereomicroscope and a scanning electron microscope (SEM) in order to analyze enamel surface and Adhesive Remnant Index (ARI). Kruskal-Wallis and Mann-Whitney (with Bonferroni correction) tests showed a significant difference between the studied groups (p < 0.05). Groups XT, QC, and SEP presented the highest values of adhesive resistance and no statistical differences were found between them. The highest frequency of failures between enamel and adhesive was observed in groups XT, QC, and OL. Quick Cure (QC) remineralizing adhesive system presented average adhesive resistance values similar to conventional (XT) and self-etching (SEP) adhesives, while remineralizing system (OL) provided the lowest values of adhesive resistance. PMID- 26380372 TI - The Lambert Way to Gaussianize Heavy-Tailed Data with the Inverse of Tukey's h Transformation as a Special Case. AB - I present a parametric, bijective transformation to generate heavy tail versions of arbitrary random variables. The tail behavior of this heavy tail Lambert W * F X random variable depends on a tail parameter delta >= 0: for delta = 0, Y = X, for delta > 0 Y has heavier tails than X. For X being Gaussian it reduces to Tukey's h distribution. The Lambert W function provides an explicit inverse transformation, which can thus remove heavy tails from observed data. It also provides closed-form expressions for the cumulative distribution (cdf) and probability density function (pdf). As a special case, these yield analytic expression for Tukey's h pdf and cdf. Parameters can be estimated by maximum likelihood and applications to S&P 500 log-returns demonstrate the usefulness of the presented methodology. The R package Lambert W implements most of the introduced methodology and is publicly available on CRAN. PMID- 26380374 TI - The Productivity Dilemma in Workplace Health Promotion. AB - BACKGROUND: Worksite-based programs to improve workforce health and well-being (Workplace Health Promotion (WHP)) have been advanced as conduits for improved worker productivity and decreased health care costs. There has been a countervailing health economics contention that return on investment (ROI) does not merit preventive health investment. METHODS/PROCEDURES: Pertinent studies were reviewed and results reconsidered. A simple economic model is presented based on conventional and alternate assumptions used in cost benefit analysis (CBA), such as discounting and negative value. The issues are presented in the format of 3 conceptual dilemmas. PRINCIPAL FINDINGS: In some occupations such as nursing, the utility of patient survival and staff health is undervalued. WHP may miss important components of work related health risk. Altering assumptions on discounting and eliminating the drag of negative value radically change the CBA value. SIGNIFICANCE: Simple monetization of a work life and calculation of return on workforce health investment as a simple alternate opportunity involve highly selective interpretations of productivity and utility. PMID- 26380375 TI - Recent Advances in General Game Playing. AB - The goal of General Game Playing (GGP) has been to develop computer programs that can perform well across various game types. It is natural for human game players to transfer knowledge from games they already know how to play to other similar games. GGP research attempts to design systems that work well across different game types, including unknown new games. In this review, we present a survey of recent advances (2011 to 2014) in GGP for both traditional games and video games. It is notable that research on GGP has been expanding into modern video games. Monte-Carlo Tree Search and its enhancements have been the most influential techniques in GGP for both research domains. Additionally, international competitions have become important events that promote and increase GGP research. Recently, a video GGP competition was launched. In this survey, we review recent progress in the most challenging research areas of Artificial Intelligence (AI) related to universal game playing. PMID- 26380373 TI - Health Behaviors and Overweight in Nursing Home Employees: Contribution of Workplace Stressors and Implications for Worksite Health Promotion. AB - BACKGROUND: Many worksite health promotion programs ignore the potential influence of working conditions on unhealthy behaviors. METHODS: A study of nursing home employees (56% nursing aides) utilized a standardized questionnaire. We analyzed the cross-sectional associations between workplace stressors and obesity, cigarette smoking, and physical inactivity. RESULTS: Of 1506 respondents, 20% reported exposure to three or more workplace stressors (physical or organizational), such as lifting heavy loads, low decision latitude, low coworker support, regular night work, and physical assault. For each outcome, the prevalence ratio was between 1.5 and 2 for respondents with four or five job stressors. Individuals under age 40 had stronger associations between workplace stressors and smoking and obesity. CONCLUSIONS: Workplace stressors were strongly associated with smoking, obesity, and physical inactivity, even among the lowest status workers. Current working conditions affected younger workers more than older workers. Although this study is cross-sectional, it has other strengths, including the broad range of work stressors studied. Strenuous physical work and psychosocial strain are common among low-wage workers such as nursing home aides. Workplace health promotion programs may be more effective if they include measures to reduce stressful work environment features, so that working conditions support rather than interfere with employee health. PMID- 26380376 TI - Multivariate Statistical Analysis as a Supplementary Tool for Interpretation of Variations in Salivary Cortisol Level in Women with Major Depressive Disorder. AB - Multivariate statistical analysis is widely used in medical studies as a profitable tool facilitating diagnosis of some diseases, for instance, cancer, allergy, pneumonia, or Alzheimer's and psychiatric diseases. Taking this in consideration, the aim of this study was to use two multivariate techniques, hierarchical cluster analysis (HCA) and principal component analysis (PCA), to disclose the relationship between the drugs used in the therapy of major depressive disorder and the salivary cortisol level and the period of hospitalization. The cortisol contents in saliva of depressed women were quantified by HPLC with UV detection day-to-day during the whole period of hospitalization. A data set with 16 variables (e.g., the patients' age, multiplicity and period of hospitalization, initial and final cortisol level, highest and lowest hormone level, mean contents, and medians) characterizing 97 subjects was used for HCA and PCA calculations. Multivariate statistical analysis reveals that various groups of antidepressants affect at the varying degree the salivary cortisol level. The SSRIs, SNRIs, and the polypragmasy reduce most effectively the hormone secretion. Thus, both unsupervised pattern recognition methods, HCA and PCA, can be used as complementary tools for interpretation of the results obtained by laboratory diagnostic methods. PMID- 26380377 TI - Factors Associated with Perforated Appendicitis in Elderly Patients in a Tertiary Care Hospital. AB - Background. The incidence of perforated appendicitis in elderly patients is high and carries increased morbidity and mortality rates. The aim of this study was to identify risk factors of perforation in elderly patients who presented with clinical of acute appendicitis. Methods. This was a retrospective study, reviewing medical records of patients over the age of 60 years who had a confirmed diagnosis of acute appendicitis. Patients were classified into two groups: those with perforated appendicitis and those with nonperforated appendicitis. Demographic data, clinical presentations, and laboratory analysis were compared. Results. Of the 206 acute appendicitis patients over the age of 60 years, perforated appendicitis was found in 106 (50%) patients. The four factors which predicted appendiceal rupture were as follows: male; duration of pain in preadmission period; fever (>38 degrees C); and anorexia. The overall complication rate was 34% in the perforation group and 12.6% in the nonperforation group. Conclusions. The incidence of perforated appendicitis in elderly patients was higher in males and those who had certain clinical features such as fever and anorexia. Duration of pain in the preadmission period was also an important factor in appendiceal rupture. Early diagnosis may decrease the incidence of perforated appendicitis in elderly patients. PMID- 26380379 TI - (-)-Oleocanthal rapidly and selectively induces cancer cell death via lysosomal membrane permeabilization. AB - (-)-Oleocanthal (OC), a phenolic compound present in extra-virgin olive oil (EVOO), has been implicated in the health benefits associated with diets rich in EVOO. We investigated the effect of OC on human cancer cell lines in culture and found that OC induced cell death in all cancer cells examined as rapidly as 30 minutes after treatment in the absence of serum. OC treatment of non-transformed cells suppressed their proliferation but did not cause cell death. OC induced both primary necrotic and apoptotic cell death via induction of lysosomal membrane permeabilization (LMP). We provide evidence that OC promotes LMP by inhibiting acid sphingomyelinase (ASM) activity, which destabilizes the interaction between proteins required for lysosomal membrane stability. The data presented here indicate that cancer cells, which tend to have fragile lysosomal membranes compared to non-cancerous cells, are susceptible to cell death induced by lysosomotropic agents. Therefore, targeting lysosomal membrane stability represents a novel approach for the induction of cancer-specific cell death. PMID- 26380378 TI - Lifestyle Modification Experiences of African American Breast Cancer Survivors: A Needs Assessment. AB - BACKGROUND: Little is known about the rates of obesity among African American (AA) breast cancer survivors (BCSs), the availability and use of lifestyle modification methods suitable for this population, and the impact of changes in dietary intake and physical activity on health-related quality of life (HR-QoL). OBJECTIVE: The objectives of the study were to describe obesity rates, dietary intake, and physical activity as lifestyle modification strategies; examine predictors of engagement in these strategies post diagnosis; and learn more about salient features of lifestyle interventions from AA BCSs participating in a breast cancer support group. METHODS: The needs assessment included four components: (1) a literature review to determine existing lifestyle modification strategies of AA BCSs; (2) secondary data analysis of the 2010 National Health Interview Survey, Cancer Control Supplement to examine HR-QoL; (3) administration, to 200 AA BCSs, of an assessment tool relating to weight and breast cancer history, dietary intake, and physical activity through a variety of approaches (eg, Internet, mail, in-person, and telephone); and (4) focus group discussions to frame lifestyle interventions. RESULTS: Preliminary findings indicate that AA BCSs are underrepresented in lifestyle intervention research, have disparities in HR-QoL outcomes, do not meet current cancer prevention guidelines, and have recommendations for effective strategies for lifestyle modification. CONCLUSIONS: As analyses of the needs assessment are completed, the research team is partnering with community coalitions and breast cancer support groups in Miami, Chicago, Houston, Los Angeles, and Philadelphia to develop community-engaged intervention approaches for promoting adherence to cancer prevention guidelines. PMID- 26380380 TI - Prospects of Cinnamon in Multiple Sclerosis. PMID- 26380381 TI - Interplay of catalytic subsite residues in the positioning of alpha-d-glucose 1 phosphate in sucrose phosphorylase. AB - Kinetic and molecular docking studies were performed to characterize the binding of alpha-d-glucose 1-phosphate (alphaGlc 1-P) at the catalytic subsite of a family GH-13 sucrose phosphorylase (from L. mesenteroides) in wild-type and mutated form. The best-fit binding mode of alphaGlc 1-P dianion had the phosphate group placed anti relative to the glucosyl moiety (adopting a relaxed 4C1 chair conformation) and was stabilized mainly by hydrogen bonds from residues of the enzyme's catalytic triad (Asp196, Glu237 and Asp295) and from Arg137. Additional feature of the alphaGlc 1-P docking pose was an intramolecular hydrogen bond (2.7 A) between the glucosyl C2-hydroxyl and the phosphate oxygen. An inactive phosphonate analog of alphaGlc 1-P did not show binding to sucrose phosphorylase in different experimental assays (saturation transfer difference NMR, steady state reversible inhibition), consistent with evidence from molecular docking study that also suggested a completely different and strongly disfavored binding mode of the analog as compared to alphaGlc 1-P. Molecular docking results also support kinetic data in showing that mutation of Phe52, a key residue at the catalytic subsite involved in transition state stabilization, had little effect on the ground-state binding of alphaGlc 1-P by the phosphorylase. However, when combined with a second mutation involving one of the catalytic triad residues, the mutation of Phe52 by Ala caused complete (F52A_D196A; F52A_E237A) or very large (F52A_D295A) disruption of the proposed productive binding mode of alphaGlc 1-P with consequent effects on the enzyme activity. Effects of positioning of alphaGlc 1-P for efficient glucosyl transfer from phosphate to the catalytic nucleophile of the enzyme (Asp196) are suggested. High similarity between the alphaGlc 1-P conformers bound to sucrose phosphorylase (modeled) and the structurally and mechanistically unrelated maltodextrin phosphorylase (experimental) is revealed. PMID- 26380382 TI - Tumor Enucleation of Renal Cell Carcinoma in a Solitary Kidney. AB - We describe the case of a 57 year old man with a solitary kidney after undergoing resection of a Wilm's tumor as a child and a recent left partial colectomy who presents with an incidentally found clinical T1b renal mass. The patient underwent tumor enucleation and had no change in his renal function twelve days after surgery as compared to his preoperative baseline, highlighting the additional nephron-sparing associated with tumor enucleation as compared to partial nephrectomy that includes a gross margin of normal parenchyma. PMID- 26380383 TI - Perception and Action in Simulated Telesurgery. AB - We studied the effect of delay on perception and action in contact with a force field that emulates elastic soft tissue with a specific rigid nonlinear boundary. Such field is similar to forces exerted on a needle during teleoperated needle insertion tasks. We found that a nonlinear boundary region causes both psychometric and motor overestimation of stiffness, and that delay causes motor but not psychometric underestimation of the stiffness of this nonlinear soft tissue. In addition we show that changing the teleoperation channel gain reduces and can even cancel the motor effect of delay. PMID- 26380384 TI - Collagenase Clostridium histolyticum for the pharmacological management of Peyronie's disease. AB - Peyronie's disease (PD) is defined as the abnormal accumulation of connective tissue in the tunica albuginea of the penis, and is an ongoing physical and psychological challenge for thousands of Americans. In vitro studies in the 1950s uncovered the potential of collagenase Clostridium histolyticum (CCH) to disrupt the collagen-containing plaques in PD, and opened the door to more in-depth clinical trials. Results indicated that with multiple dosage cycles followed by plaque modeling, penile curvature can be corrected, on average, in up to 35% of cases, with the majority of patients achieving >= 25% improvement in penile curvature. Most studies also indicated an improvement in patient-reported symptoms from the Peyronie's Disease Questionnaire. Adverse events from treatment with CCH included penile bruising, pain and edema, but most were mild to moderate in severity and usually resolved without intervention, suggesting that CCH is an effective and safe treatment for PD. PMID- 26380385 TI - Fluticasone furoate/vilanterol combination for the treatment of COPD and asthma. AB - The critical role of the combination therapy of an inhaled corticosteroid (ICS) and a long-acting beta-adrenoceptor agonist (LABA) in the treatment of patients suffering from asthma and also severe chronic obstructive pulmonary disease (COPD) patients with frequent exacerbations explains why there is a strong interest within the pharmaceutical industry in developing a once-daily ICS/LABA fixed-dose combination (FDC), in an attempt to simplify the treatment and, consequently, increase adherence to the prescribed therapy, and also to overcome the loss of patent protection. GlaxoSmithKline and Theravance have developed an inhaled FDC of the ICS fluticasone furoate (FF) and the LABA vilanterol (VI) as a once-daily treatment for asthma and COPD. FF/VI, by simplifying the dosing schedule, allows, for the first time, a shift from twice-daily to once-daily treatment, with an acceptable safety and tolerability profile that is consistent with the ICS/LABA class. The decision to prescribe FF/VI rather than another ICS/LABA FDC is likely to be based on the patient's preference for the inhaler device, their ability to use the device correctly and the convenience of once daily dosing frequency as well as comparative costs with other combination products. However, further studies are required to specifically assess these possibilities. PMID- 26380386 TI - Naloxegol: the first orally administered, peripherally acting, mu opioid receptor antagonist, approved for the treatment of opioid-induced constipation. AB - Treatment of opioid-induced constipation (OIC) is becoming a relevant clinical challenge as most of the treatments demonstrated to be more effective than placebo in treating OIC have safety issues limiting a broad clinical application. Naloxegol is the first orally administered, peripherally acting, u opioid receptor antagonist approved by the FDA and EMA specifically for the treatment of noncancer patients with OIC. This review summarizes the results of the studies regarding the effects of naloxegol in OIC. Pharmacodynamic studies have demonstrated that naloxegol was able to inhibit gastrointestinal opioid effects while preserving central analgesic actions. Phase II and phase III studies in patients with noncancer OIC have confirmed the efficacy of naloxegol to inhibit OIC, and the most consistent efficacy was seen with the 25-mg dose once daily. Side effects were mainly gastrointestinal in origin (and usually transient and mild) and there were no signs of opioid withdrawal in the studies. Safety and tolerability were shown in a long-term safety study. Considering its efficacy, safety, route of administration and the limitations of most of the other available treatments, naloxegol has the potential to become the first-line treatment for noncancer patients with OIC. PMID- 26380387 TI - Panobinostat, a pan-histone deacetylase inhibitor: rationale for and application to treatment of multiple myeloma. AB - Histone deacetylase inhibitors (HDACis) have emerged as novel therapeutic agents for cancer. Currently, four HDACis are approved by the Food and Drug Administration (FDA) to treat various hematologic malignancies. Panobinostat (LBH 589, trade name Farydak(r), developed and marketed by Novartis) is a potent pan HDACi with demonstrated anticancer activities against multiple myeloma, a B-cell malignancy, at a low nanomolar range in preclinical settings, and in 2015 was granted FDA approval for the treatment of relapsed and refractory multiple myeloma. Here, we review the development of HDACis, the unique features of panobinostat, and the rationale for developing panobinostat in a combination setting for the treatment of multiple myeloma. We also review the completed and ongoing clinical trials testing the efficacy of panobinostat in combination therapies and highlight future therapeutically relevant strategies. PMID- 26380389 TI - Role of the NLRP3 inflammasome in the progression of nonalcoholic fatty liver disease to nonalcoholic steatohepatitis. PMID- 26380388 TI - Drug-device combination products: regulatory landscape and market growth. AB - Combination products are therapeutic and diagnostic products that combine drugs, devices and/or biological products, leading to safer and more effective treatments thanks to careful and precise drug targeting, local administration and individualized therapy. These technologies can especially benefit patients suffering from serious diseases and conditions such as cancer, heart disease, multiple sclerosis and diabetes, among others. On the other hand, drug-device combination products have also introduced a new dynamic in medical product development, regulatory approval and corporate interaction. Due to the increasing integration of drugs and devices observed in the latest generation of combination products, regulatory agencies have developed specific competences and regulations over the last decade. Manufacturers are required to fully understand the specific requirements in each country in order to ensure timely and accurate market access of new combination products, and the development of combination products involves a very specific pattern of interactions between manufacturers and regulatory agencies. The increased sophistication of the products brought to market over the last couple of decades has accentuated the need to develop drugs and devices collaboratively using resources from both industries, fostering the need of business partnering and technology licensing. This review will provide a global overview of the market trends, as well as (in the last section) an analysis of the drug-device combination products approved by the FDA during the latest 5 years. PMID- 26380390 TI - The Role of Scientific Collections in Scientific Preparedness. PMID- 26380391 TI - Response to Comment on "Release of Arsenic to the Environment from CCA-Treated Wood. 2. Leaching and Speciation during Disposal". PMID- 26380393 TI - Factors Influencing the Management of Chronic Orofacial Pain and Headche. PMID- 26380392 TI - [Editorial note]. PMID- 26380395 TI - [The new concept of the Journal of Czech Physicians]. PMID- 26380394 TI - [Personalities in the history of medicine. Iwan Petrowitsch Pawlow]]. PMID- 26380396 TI - HONE IN ON THE RANGE. PMID- 26380397 TI - Diabetes Management: It Takes a Team. PMID- 26380398 TI - Diabetic Cooking. PMID- 26380399 TI - Which outcomes? PMID- 26380400 TI - Welcome to Diabetes. PMID- 26380402 TI - [Progress in synthetic biology of pinocembrin]. AB - Pinocembrin, belonging to flavanons, was isolated from various plants. Pinocembrin has a variety of pharmacological activities, such as neuroprotective effect, antimicrobial activity, and antioxidant efficacy. Pinocembrin was approved as class I drugs to its phase II clinical trial by CFDA in 2009, mainly used for the treatment of ischemic stroke. As a promising compound, the manufacturing technologies of pinocembrin, including chemical synthesis, extraction from plant and synthetic biology, have attracted many attentions. Compared with the first two technologies, synthetic biology has many advantages, such as environment-friendly and low-cost. Construction of biosynthetic pathway in microorganism offers promising results for large scale pinocembrin production by fermentation after taking lots of effective strategies. This article reviews some of recent strategies in microorganisms to improve the yield, with focus on the selection of appropriate the key enzyme sources, the supply of precursors and cofactors by microorganisms, the choice of substance and the level of the key enzyme expression. PMID- 26380403 TI - [Progress in molecular biology of a semi-mangrove, Millettia pinnata]. AB - Millettia pinnata L. is a leguminous tree with great potential in biodiesel applications and also a typical semi-mangrove. In this review, we presented several aspects about the recent research progress in molecular biology of M. pinnata. We descrived several types of molecular markers used to assess the genetic diversity and phylogeny of this species, genome and transcriptome analyses based on high-throughput sequencing platform accomplished for this species, and several gene and genomic sequences of this species isolated for further research. Finally, based on the current research progress, we proposed some orientations for future molecular biology research on M. pinnata. PMID- 26380404 TI - [Progress in co-immobilization of multiple enzymes]. AB - Enzyme immobilization is the core technology of biocatalysis. Over the past few decades, enzyme immobilization research mainly focused on single enzyme immobilization. In recent years, multi-enzyme immobilization attracts more and more attention as it could increase the local concentration of reaction and improve the reaction yield. In this review, a summary of the recent progress, together with our research, is presented. Special emphasis is placed on four methods in multi-enzymes co-immobilization, namely, the nonspecific covalent co immobilization, the nonspecific non-covalent co-immobilization, the non-covalent encapsulation co-immobilized and the site specificity co-immobilized. Finally, some industrial uses of immobilized multi-enzymes were addressed and the application prospect of multi-enzyme immobilization was highlighted. PMID- 26380405 TI - [Progress in glucaric acid]. AB - Glucaric acid (GA) is derived from glucose and commonly used in chemical industry. It is also considered as one of the "Top value-added chemicals from biomass" as carbohydrate monomers to produce various synthetic polymers and bioenergy. The demand for GA in food manufacture is increasing. GA has also attracted public attentions due to its therapeutic uses such as regulating hormones, increasing the immune function and reducing the risks of cancers. Currently GA is produced by chemical oxidation. Research on production of GA via microbial synthesis is still at preliminary stage. We reviewed the advances of glucaric acid applications, preparation and quantification methods. The prospects on production of GA by microbial fermentation were also discussed. PMID- 26380406 TI - [Cloning and regulation of pig estrogen related receptor beta gene (ESRRB) promoter]. AB - The estrogen related receptor family member Esrrb (Estrogen related receptor beta) is a gene that expresses in the early stage of embryo and plays an important role in the core pluripotent network. Its function has been analyzed in human and mouse, although no report so far related to pig. Therefore, to explore its mechanism of transcriptional regulation and expression pattern, we cloned a 3.3 kb pig ESRRB promoter by PCR and constructed the green fluorescence protein (GFP) reporter vector pE3.3. We used these vectors to study the ESRRB expression pattern in 293T, Hela and C2C12. Sequence was analyzed for regulatory elements that share homology to known transcription factor binding sites by TFSEARCH and JASPER program. Some pluripotency related genes such as SMAD, STAT3, MYC, KLF4 and ESRRB have been found within the 3.3 kb sequence by co-transfected pig ESRRB promoter and these potential regulators. We found that ESRRB only expressed in 293T and SMAD could activate ESRRB expression obviously. To determine the core promoter region, a series of ESRRB promoter fragments with gradually truncated 5' end were produced by PCR and inserted into pGL3-Basic vector. After transient transfection into 293T, dual luciferase assay was used to measure these promoter activities. The result suggested that the core promoter of pig ESRRB located within -25 bp to -269 bp region. These results suggest that these transcription factor binding sites and the core promoter region may be essential for transcriptional regulation of pig ESRRB gene. PMID- 26380407 TI - [Cloning, expression of gene SjOST48 from Schistosoma japonicum and evaluation of the immunoprotective efficacy of rSjOST48 in mice]. AB - To identify SJCHGC01743 gene of Schistosoma japonicum and evaluate the potential of the recombinant protein as a new vaccine candidate for schistosomiasis, polymerase chain reaction (PCR) technique was used to amplify the cDNA of the gene and real-time RT-PCR was used to analyze the transcription profiles of SJCHGC01743 at different development stages. Recombinant plasmid was successfully constructed and transformed into competent Escherichia coli BL21 (DE3). Then the recombinant protein was expressed, purified and emulsified with ISA206 adjuvant to immunize BALB/c mice for three times. The immunogenicity was confirmed by Western blotting and tissue localization was detected by indirect immunofluorescent assay. The specific antibody level was detected by ELISA. The immunoprotection of rSjOST48 was evaluated by the reduction in worm and egg counts in mice. A cDNA with 1 248 nucleotides was isolated from 28-day-old schistosomes cDNAs by PCR. Sequence analysis revealed that SJCHGC01743 was a 48 kDa subunit of the oligosaccharyltransferase complex (OST48) and named as SjOST48. Real-time PCR analysis indicated that this gene was expressed in all investigated stages and had the highest expression level in 28 d worms, the level of gene transcription in female worms was significantly higher than that of male worms. Then recombinant plasmid pET28a(+)-SjOST48 was successfully constructed and expressed in E. coli BL21 (DE3). Western blotting analysis showed that rSjOST48 had good immunogenicity. Indirect immunofluorescent analysis revealed that SjOST48 was mainly distributed on the tegument of the worms. The result of ELISA indicated that the rSjOST48 vaccinated group could induce a significant increase in the level of specific IgG, IgG1 and IgG2a. An immunoprotection experiment showed that the vaccination of rSjOST48 in mice induced 32.62% (P < 0.05) reduction in the numbers of worms and 57.61% (P < 0.01) in eggs in liver, compared with that of the control group. This study provides the foundation for proceeding further research on the biological function of SjOST48 and screening new vaccine candidates for schistosomiasis. PMID- 26380408 TI - Molecular cloning and over-expression of a fructosyltransferase from Aspergillus niger QU10. AB - The main commercial production of fructooligosaccharides (FOS) comes from enzymatic transformation using sucrose as substrate by microbial enzyme fructosyltransferase. A fructosyltransferase genomic DNA was isolated from Aspergillus niger QU10 by PCR. The nucleotide sequence showed a 1 941 bp size, and has been submitted to GenBank (KF699529). The cDNA of the fructosyltransferase, containing an open reading frame of 1 887 bp, was further cloned by RT-PCR. The fructosyltransferase gene from Aspergillus niger was functionally expressed both in Escherichia coli and Pichia pastoris GS 115. The highest activity value for the construction with the alpha-factor signal peptide reached 431 U/mL after 3 days of incubation. The recombinant enzyme is extensively glycosylated, and the active form is probably represented by a homodimer with an apparent molecular mass of 200 kDa as judged from mobility in seminative PAGE gels. The extracellular recombinant enzyme converted sucrose mostly to FOS, mainly 1-kestose and nystose, liberating glucose. FOS reached a maximal value and represented about 58% of total sugars present in the reaction mixture after 4 h reaction. The results suggest that the availability of recombinant Pichia pastoris as a new source of a FOS-producing enzyme might result of biotechnology interest for industrial application. PMID- 26380409 TI - [Accumulation of 9alpha-hydroxy-4-androstene-3,17-dione by co-expressing kshA and kshB encoding component of 3-ketosteroid-9alpha-hydroxylase in Mycobacterium sp. NRRL B-3805]. AB - 9alpha-hydroxy-4-androstene-3,17-dione (9-OH-AD) is an important intermediate in the steroidal drugs production. 3-ketosteroid-9alpha-hydroxylase (KSH), a two protein system of KshA and KshB, is a key-enzyme in the microbial steroid ring B opening pathway. KSH catalyzes the transformation of 4-androstene-3,17-dione (AD) into 9-OH-AD specifically. In the present study, the putative KshA and KshB genes were cloned from Mycobacterium smegmatis mc(2)155 and Gordonia neofelifaecis NRRL B-59395 respectively, and were inserted into the expression vector pNIT, the co expression plasmids of kshA-kshB were obtained and electroporated into Mycobacterium sp. NRRL B-3805 cells. The recombinants were used to transform steroids, the main product was characterized as 9alpha-hydroxy-4-androstene-3,17 dione (9-OH-AD), showing that kshA and kshB were expressed successfully. Different from the original strain Mycobacterium sp. NRRL B-3805 that accumulates 4-androstene-3,17-dione, the recombinants accumulates 9alpha-hydroxy-4-androstene 3,17-dione as the main product. This results indicates that the putative genes kshA, kshB encode active KshA and KshB, respectively. The process of biotransformation was investigated and the results show that phytosterol is the most suitable substrate for biotransformation, kshA and kshB from M. smegmatis mc(2)155 seemed to exhibit high activity, because the resultant recombinant of them catalyzed the biotransformation of phytosterol to 9-OH-AD in a percent conversion of 90%, which was much higher than that of G. neofelifaecis NRRL B 59395. This study on the manipulation of the ksh genes in Mycobacterium sp. NRRL B-3805 provides a new pathway for producing steroid medicines. PMID- 26380410 TI - [Succinic acid production from sucrose and sugarcane molasses by metabolically engineered Escherichia coli]. AB - Sugarcane molasses containing large amounts of sucrose is an economical substrate for succinic acid production. However, Escherichia coli AFP111 cannot metabolize sucrose although it is a promising candidate for succinic acid production. To achieve sucrose utilizing ability, we cloned and expressed cscBKA genes encoding sucrose permease, fructokinase and invertase of non-PTS sucrose-utilization system from E. coli W in E. coli AFP111 to generate a recombinant strain AFP111/pMD19T-cscBKA. After 72 h of anaerobic fermentation of the recombinant in serum bottles, 20 g/L sucrose was consumed and 12 g/L succinic acid was produced. During dual-phase fermentation comprised of initial aerobic growth phase followed by anaerobic fermentation phase, the concentration of succinic acid from sucrose and sugarcane molasses was 34 g/L and 30 g/L, respectively, at 30 h of anaerobic phase in a 3 L fermentor. The results show that the introduction of non-PTS sucrose-utilization system has sucrose-metabolizing capability for cell growth and succinic acid production, and can use cheap sugarcane molasses to produce succinic acid. PMID- 26380411 TI - [Agrobacterium-mediated transformation of Cymbidium sinensis]. AB - Genetic transformation is an effective method to improve breeding objective traits of orchids. However, there is little information about genetic transformation of Cymbidium sinensis. Rhizomes from shoot-tip culture of C. sinensis cv. 'Qijianbaimo' were used to establish a practical transformation protocol of C. sinensis. Pre-culture time, concentration and treating methods of acetosyringone, concentration of infection bacteria fluid (OD600), infection time, and co-culture time had significant effects on beta-glucuronidase (GUS) transient expression rate of C. sinensis cv. 'Qijianbaimo' rhizome. The GUS transient expression rate of rhizome was the highest (11.67%) when rhizomes pre cultured for 39 d were soaked in bacterium suspension (OD600 = 0.9) supplemented with 200 MUmol/L acetosyringone for 35 min, followed by culturing on co-culture medium supplemented with 200 MUmol/L acetosyringone for 7 d. Under this transformation conditions, 3 transgenic plantlets, confirmed by GUS histochemical assay and PCR, were obtained from 400 regenerated plantlets, and the genetic transformation rate was 0.75%. This proved that it was feasible to create new cultivars by the use of Agrobacterium-mediated genetic transformation in C. sinense. PMID- 26380412 TI - [Identifying transcription factors involved in Arabidopsis adventious shoot regeneration by RNA-Seq technology]. AB - Transcriptional regulation is one of the major regulations in plant adventious shoot regeneration, but the exact mechanism remains unclear. In our study, the RNA-seq technology based on the IlluminaHiSeq 2000 sequencing platform was used to identify differentially expressed transcription factor (TF) encoding genes during callus formation stage and adventious shoot regeneration stage between wild type and adventious shoot formation defective mutant be1-3 and during the transition from dedifferentiation to redifferentiation stage in wildtype WS. Results show that 155 TFs were differentially expressed between be1-3 mutant and wild type during callus formation, of which 97 genes were up-regulated, and 58 genes were down-regulated; and that 68 genes were differentially expressed during redifferentiation stage, with 40 genes up-regulated and 28 genes down-regulated; whereas at the transition stage from dedifferentiation to redifferention in WS wild type explants, a total of 231 differentially expressed TF genes were identified, including 160 up-regualted genes and 71 down-regulated genes. Among these TF genes, the adventious shoot related transcription factor 1 (ART1) gene encoding a MYB-related (v-myb avian myeloblastosis viral oncogene homolog) TF, was up-regulated 3 217 folds, and was the highest up-regulated gene during be1-3 callus formation. Over expression of the ART1 gene caused defects in callus formation and shoot regeneration and inhibited seedling growth, indicating that the ART1 gene is a negative regulator of callus formation and shoot regeneration. This work not only enriches our knowledge about the transcriptional regulation mechanism of adventious shoot regeneration, but also provides valuable information on candidate TF genes associated with adventious shoot regeneration for future research. PMID- 26380413 TI - [Optimized expression, preparation of human papillomavirus 16 L2E7 fusion protein and its inhibitory effect on tumor growth in mice]. AB - HPV16 L2E7 is a fusion protein used for therapeutical vaccine targeting HPV virus. To increase its expression in Escherichia coli, we optimized the codon usage of HPV16 l2e7 gene based on its codon usage bias. The optimized gene of HPV16 sl2e7 was cloned into three different vectors: pGEX-5X-1, pQE30, ET41a, and expressed in JM109, JM109 (DE3) and BL21 (DE3) lines separately. A high expression line was selected with pET41a vector in BL21 (DE3) cells. After optimization of the growth condition, including inoculation amount, IPTG concentration, induction time and temperature, the expression level of HPV16 L2E7 was increased from less than 10% to about 28% of total protein. HPV16 L2E7 protein was then purified from 15 L culture by means of SP Sepharose Fast Flow, Q Sepharose Fast Flow and Superdex 200 pg. After renaturing, HPV16 L2E7 protein with >= 95% purity was achieved, which was confirmed via SDS-PAGE gel and Western blotting. The combined use of purified HPV16 L2E7 and CpG helper has shown clear inhibition of tumor growth in mice injected with tumor cells, with six out of eight mice shown no sign of tumor. This study lays a solid foundation for a new pipeline of large-scale vaccine production. PMID- 26380414 TI - [Optimization and application of targeted LC-MS metabolomic analyses in photosynthetic cyanobacteria]. AB - To accurately analyze metabolites in industry-important photosynthetic microbes, LC-MS based metabolomics protocol needs to be optimized specifically for individual species. In this study, an LC-MS based metabolomics method was optimized for cyanobacterium Synechocystis sp. PCC 6803. With the optimized extraction, liquid chromatographic and mass spectral parameters, the method was capable of detecting 24 important metabolites related to central carbohydrate and energy metabolism in Synechocystis sp. PCC 6803. The study laid an important foundation for the metabolomics analysis of cyanobacteria. PMID- 26380415 TI - [Modified baculovirus system for high expression of Bombyx mori bidensovirus NS1 in silkworm]. AB - To improve the expression of heterologous genes using baculovirus expression system, we constructed a novel shuttle vector based on the Bm-Bacmid. In the Bm Bacmid, partial sequences of Chitinase and Cystein Protease were replaced with a tandem cassette of Cm and egfp through homologous recombination. Bombyx mori bidensovirus (BmBDV) ns1 under the control of polyhedrin promoter was inserted into the modified Bm-bacmid by transposition. For comparison, BmBDV ns1 under the control of polyhedrin promoter was also cloned in the wild type Bm-bacmid. The resulting Bm-bacmids were transfected into the cultured BmN cells to prepare recombinant virus to infect silkworms for expression of BmBDV ns1. Total proteins of hemocyte from infected silkworms were subjected to Western blotting and ELISA analysis. The yield of BmBDV NS1 1 with the modified vector was three times as much as that with the unmodified vector. The method to improve the yield of BmBDV NS1 in silkworms will facilitate the function and three-dimensional structure study of BmBDV NS1. PMID- 26380416 TI - [THE ROLE OF beta-AMYLOID AND MITOCHONDRIAL DYSFUNCTION IN THE PATHOGENESIS OF ALZHEIMER'S DISEASE]. AB - Alzheimer's disease is the most common form of dementia in mid- and late life. The 7-10% of the population over 65 and the 50-60% of the population over 85 are affected by this disease. In spite of its prevalence, the pathogenesis of the disease is not well defined and there is no effective neuroprotective therapeutic agent. Three predominant neuropathologic features of the brain in Alzheimer disease are: the intracellular neurofibrillary tangles consisting mainly of the hyperphosphorylated protein tau; the extracellular amyloid deposits (neuritic plaques) consisting of amyloid beta peptide; and the extensive neuronal cell loss in the hippocampus and in portions of the cerebral cortex. The possible reason of the extensive neuronal cell loss can be the mitochondrial dysfunction observed in Alzheimer's disease. Beyond the uncertain pathogenesis, the causality of these characteristic neuropathologic phenomena are still unknown. In this study we present two hypotheses, one of the amyloid cascade and one of the mitochondrial cascade. We give an overview of these two hypotheses and discuss their correlations. PMID- 26380417 TI - [RADIOSURGERY OF INTRACEREBRAL CAVERNOMAS--CURRENT INTERNATIONAL TRENDS]. AB - Although still a controversial management option, radio-surgery of intracranial cavernomas has become increasingly popular world-wide during the last decade. Microsurgery is a safe and effective treatment for symptomatic hemispheric cavernomas. However, the indication for microsurgical resection of deep eloquent cavernomas is relatively limited even in experienced hands. The importance of radiosurgery has recently been appreciated in parallel with increasing positive experiences both in terms of effectiveness and safety, especially for cases high risk for surgical resection, in the brainstem, thalamus and basal ganglia. While radiosurgery was earlier indicated mainly for surgically inaccessible lesions that had bled multiple times, a more proactive policy has recently become more accepted. In our opinion preventive treatment with the low morbidity radiosurgery serves the patients' interest especially for deep eloquent lesions that had bled not more than once, due to the cumulative morbidity of repeated hemorrhages. Despite our increasing knowledge on natural history, there is currently no available treatment algorithm for cavernomas. Arguments for all three treatment modalities (observation, microsurgery and radiosurgery) are established, but their indication criteria are yet to be defined. It is time to organize a prospective population based data collection in Hungary, which appears to be the most realistic way to clarify indication criteria. PMID- 26380418 TI - [RADIOSURGERY OF INTRACEREBRAL CAVERNOMAS--CURRENT HUNGARIAN PRACTICE]. AB - BACKGROUND AND PURPOSE: Radiosurgery is an increasingly popular treatment option especially for deep eloquent intracerebral cavernomas that are often too risky for surgical removal, but their re-bleed carries significant risk for persisting neurological deficit. Gamma-radiation based radiosurgery has been being available since 2007 in Hungary in Debrecen. Our aim is to summarize our experience accumulated during the first five years of treatment and to compare it to the international experience. PATIENT SELECTION AND METHODS: We retrospectively analyzed 51 cavernomas in 45 patients treated between 2008 and 2012 in terms of localization, natural history, and the effect of radiosurgery on re-bleed risk and epilepsy, and its side effects. RESULTS: We treated 26.5% deep eloquent (brainstem, thalamic/basal ganglia) and 72.5% superficial hemispheric cavernomas. The median presentation age was 25 years (13-60) for deep, and 45 years (6-67) for superficial cavernomas. They were treated median of 1 year after presentation. 64.5% of deep cavernomas bled before treatment, the annual risk of first hemorrhage was 2%/lesion, re-bleed risk 21.7%, with 44% persisting morbidity. 13.5% of superficial cavernomas bled prior to treatment, the risk of first bleed was 0.3%, there was no re-bleed, and 35% caused epilepsy. We used GammaART-6000TM rotating gamma system for treatment, marginal dose was 14 Gy (10 16), and treatment volume 1.38-1.53 cm3. Re-bleed risk of deep eloquent lesions fell to 4% during the first two years after treatment and to 0% thereafter, and no hemorrhage occurred from superficial lesions after treatment. Persisting morbidity in deep lesions came from adverse radiation effect in 7% and from re bleed in 7%, and there was no persisting side effect in superficial cavernomas. 87.5% of cases of epilepsy resistant to medical therapy improved. Radiological regression was found in 37.5% and progression in 2% after treatment. CONCLUSIONS: Radiosurgery of cavernomas is safe and effective. Early preventive treatment for deep cavernomas carrying high surgical risk is justified. Moreover, for superficial lesions that are surgically easily accessible radiosurgery also appears to be an attractive alternative. PMID- 26380419 TI - [NEUROINTERVENTIONAL TREATMENT OF ACUTE ISCHEMIC STROKE: OUR EXPERIENCE IN KAPOSVAR, HUNGARY]. AB - AIM OF THE STUDY: In the present study, we report procedural and mid-term functional outcome data on the first 50 neurointerventional treatments of acute ischemic stroke in the Kaposi Mor County Hospital, Kaposvar, Hungary. MATERIALS AND METHODS: Endovascular recanalization of occluded large cervical and intracranial arteries was performed following an unsuccessful intravenous lysis or when intravenous lysis was contraindicated. A control cohort was retrospectively formed by analyzing data of 16 patients who has been unsuccesfully treated with iv. lysis before neurointervention was available in our hospital. RESULTS AND CONCLUSION: Recanalization rate was 84% and major complication rate was 2% in the neurointerventional group. Mid-term good functional outcome, defined as mRS 0-2, was achieved in 44% in the neurointerventional and in 13% in the intravenous lysis group, after 11.5 and 39.7 months follow-up period, respectively. Subgroup analysis revealed patient age as the strongest predictive factor of good functional outcome. Our data shows that neurointerventional treatment of acute ischemic stroke gives substantially improved functional outcome, in accordance with the results of the recently published international randomized trials. PMID- 26380420 TI - MENTAL HEALTH OF PHYSICIANS--NATIONWIDE REPRESENTATIVE STUDY FROM HUNGARY. AB - BACKGROUND AND AIM: Somatic and mental health and stress factors of physicians became an issue of growing interest in both national and international investigations. Our aim is to give an overview of the mental state of Hungarian physicians. METHODS: Cross-sectional, quantitative survey on a representative sample of Hungarian physicians (n = 4784). The control group was formed by the population group of a national survey conducted by "Hungarostudy 2013" (n = 2000). RESULTS: Suicidal thoughts (18.8% vs. 9.6%, p < 0.001), the scores of Somatic Symptom Scale (PHQ-10, 20.4% vs. 13.6%, p < 0.001) were significantly higher among physicians. The suicidal attempts (1.9% vs. 3.5%, p = 0.053) and BDI depression scores (7.9% vs. 29.5%, p < 0.001) were significantly higher in the control group. High Perceived Stress Scale (PPS) scores occurred in 43.3% of the physicians sample, and 43.4% of them had high scores in the Athenian Insomnia Scale (AIS). The young (< 35) female physicians showed significantly higher rates of suicidal thoughts, higher scores of PHQ and PPS. In the young female cohort, the AIS scores were significantly higher than of the other physicians. CONCLUSIONS: Mental health of physicians (sleep disorders, suicidal thoughts and psychosomatic symptoms) showed poorer results than the population data. BDI scores and the rate of suicidal attempts showed favourable trends. The next step in the research of physicians' mental health is to investigate the most serious risk factors, and to refine the preventive tools. PMID- 26380421 TI - THROMBOCYTOPENIA WITH GABAPENTIN USAGE. AB - Gabapentin is an antiepileptic drug approved for adjunctive therapy for partial seizures. We report a case of a patient who had thrombocytopenia with the dose of 2400 mg/day of gabapentin. The causal relationship between gabapentin and thrombocytopenia was revealed by dramatic increase in thrombocyte count following the cessation of the gabapentin treatment. To our knowledge, this is the first case report with a hematopoietic side effect of gabapentin. PMID- 26380422 TI - [TREATMENT OF POST-SPONDYLODESIS, ADJACENT-SEGMENT DISEASE WITH MINIMALLY INVASIVE, ANTEROLATERAL SURGERY ON THE LUMBAR SPINE: IS THERE IS NO NEED FOR DORSAL OPERATION?]. AB - Adjacent segment disease (ASD) occurs with a probability of 30% in the lumbar spine following spinal fusion surgery. Usually advanced degenerative changes happen cranially to the fused lumbar segment. Thus, secondary spinal instability, stenosis, spodylolisthesis, foraminal stenosis can lead to the recurrence of the pain not always amenable to conservative measures. A typical surgical solution to treat ASD consists of posterior revision surgery including decompression, change or extension of the instrumentation and fusion to the rostral level. It results in a larger operation with considerable risk of complications. We present a typical case of ASD treated surgically with a new minimally invasive method not yet performed in Hungary. We use anterolateral abdominal muscle splitting approach to reach the lumbar spine through the retroperitoneum. A discectomy is performed by retracting the psoas muscle dorsally. The intervertebral bony fusion is achieved by implanting a cage with large volume that is stuffed with autologous bone or tricalcium phosphate. A cage with large volume results in excellent annulus fibrosus tension, immediate stability and provides large surface for bony fusion. A stand-alone cage construct can be supplemented with lateral screw/rod/plate fixation. The advantage of the new technique for the treatment of ASD includes minimal blood loss, short operation time, significantly less postoperative pain and much lower complication rate. PMID- 26380423 TI - [LGI1 ENCEPHALITIS: THE FIRST HUNGARIAN PATIENT]. AB - In the recent years, it has been increasingly recognised that in a group of limbic encephalitis antibodies are directed against the scaffolding protein LGI1 (Leucine-rich glioma inactivated 1), which is part of the voltage gated potassium channel (VGKC) complex on neural synapses. Patients present with seizures and subacute history of neuropsychiatric symptoms, including psychosis and changes in memory, cognition, behaviour. Faciobrachial dystonic seizures can be observed, which are highly characteristic for LGI1 encephalitis. MRI shows medial temporal abnormalities in more than half of the cases. CSF evaluation is usually normal. Hyponatremia is frequently associated and may confuse the initial diagnosis. Early recognition and prompt initiation of immunotherapies are of great importance. The clinical improvements often correlate with the antibody levels. We present the case of a 64-year old man, who responded quickly to plasma exchange and major improvement was noted within few weeks. PMID- 26380424 TI - [FOCAL MOTOR SEIZURES AND STATUS EPILEPTICUS PROVOKED BY MIRTAZAPINE]. AB - The seizure-provoking effect of the tetracyclic antidepressant mirtazapine is not a well-known adverse effect of the drug. The authors report on a 39-year-old non epileptic patient who had been treated for depression with the usual daily dose of mirtazapine. Having increased the daily dose of the drug from 30 to 45 milligrams he experienced a few clonic seizures of the right lower limb. This symptom and insomnia erroneously intended the patient to further increase the daily dose of mirtazapine, which immediately resulted in the evolution of focal clonic status epilepticus in the same limb. After admission, this condition was recorded by video-EEG and abolished by intravenous administration of levetiracetam after the intravenous clonazepam had been ineffective. Discontinuation of mirtazapine and administration of carbamazepine resulted in completely seizure-free state that persisted even after carbamazepine treatment was terminated. The clinical and laboratory data indicate the seizure-provoking effect of mirtazapine in the reported case. PMID- 26380425 TI - The Hidden Curriculum. PMID- 26380426 TI - Fighting Addiction. PMID- 26380427 TI - Relationship Between Severity of Illness and Length of Stay on Costs Incurred During a Pediatric Critical Care Hospitalization. AB - OBJECTIVE: To estimate the impact of severity of illness and length of stay on costs incurred during a pediatric intensive care unit (PICU) hospitalization. STUDY DESIGN: This is a retrospective cohort study at an academic PICU located in the U.S. that examined 850 patients admitted to the PICU from Jan. 1 to Dec. 31, 2009. The study population was segmented into three severity levels based on pediatric risk of mortality (PRISM) III scores: low (PRISM score 0), medium (PRISM score 1-5), and high (PRISM score greater than 5). Outcome measures were total and daily PICU costs (2009 U.S. dollars). RESULTS: Eight hundred and fifty patients were admitted to the PICU during the study period. Forty-eight patients (5.6 percent) had incomplete financial data and were excluded from further analysis. Mean total PICU costs for low (n = 429), medium (n = 211), and high (n = 162) severity populations were $21,043, $37,980, and $55,620 (p < 0.001). Mean daily PICU costs for the low, medium, and high severity groups were $5,138, $5,903, and $5,595 (p = 0.02). CONCLUSIONS: Higher severity of illness resulted in higher total PICU costs. Interestingly, although daily PICU costs across severity of illness showed a statistically significant difference, the practical economic difference was minimal, emphasizing the importance of length of stay to total PICU costs. Thus, the study suggested that reducing length of stay independent of illness severity may be a practical cost control measure within the pediatric intensive care setting. PMID- 26380428 TI - An Unusual Case of Licorice-Induced Hypertensive Crisis. AB - BACKGROUND: Black licorice induced hypertension is an uncommon cause of hypertension in modern times because newer types of licorice rarely use the active ingredients in licorice root in large quantities. However, certain licorices and candies still contain glycyrrhizic acid (GZA) in sufficient quantities to affect blood pressure and cause other health issues. CASE: A 65 year-old woman with previously well controlled hypertension on a single medication presented to the emergency room with acute, symptomatic hypertension with blood pressures running 200s/140s. Despite IV medications, her hypertension remained refractory to treatment. This prompted a hospital admission with treatment using nicardipine in the ICU. Her blood pressure was difficult to control without a short acting antihypertensive medication infusion. She required a seven-day hospitalization (five of which were in the ICU) until her symptoms and hypertension were controlled with a three-drug regimen. Labs were notable for potassium's running on the low side of normal and low levels of both renin (less than 0.6 with normal less than or equal to 0.6-3.0) and aldosterone (1.0 with normal 3-16 ng/dL). Ten days after discharge, she was having symptomatic hypotension and was seen in the clinic. She in fact was eating large amounts of Snaps licorice which uses its original 1930s recipe including licorice granules. Her licorice habit abruptly started six months prior and included a minimum of two to four boxes per day every day. CONCLUSION/DISCUSSION: The patient currently is doing well and is down to only two antihypertensive medications at lower doses. She has given up her licorice habit. Natural licorice is extracted from Glycyrrhiza glabra root containing glycyrrhizin or glycyrrhizic acid (GZA). GZA inhibits the type 2 isoenzyme of 11 beta-hydroxysteroid dehydrogenase (11 beta HSD), which prevents local inactivation of cortisol, specifically in the renal collecting tubules. There is increased availability of cortisol to bind to renal mineralocorticoid receptors resulting in excess mineralocorticoid activity or pseudohyperaldosteronism. The patient may present with findings similar to primary aldosteronism: hypertension with sodium retention, edema, hypokalemia, metabolic alkalosis and low plasma renin activity. Plasma aldosterone levels would be low (in primary aldosteronism it is elevated). Specific testing can be performed, but resolution of symptoms after the patient stops eating licorice strongly suggests the diagnosis. PMID- 26380429 TI - Influence of Resident Physician "Moonlighting" Activities on Educational Experience and Practice Choice. AB - OBJECTIVES: Moonlighting by resident physicians, though a long-standing practice in the U.S., is a controversial topic. Conflicting claims of both detriment and benefit to resident education have been made. In this study, we sought to evaluate practicing family physicians' perceptions of the influence of moonlighting during their residency on their educational experience and selection of future practice site. METHODS: Graduates of two Midwestern family medicine residency programs in the U.S., one located in a metropolitan area of a populous state, one from a small city in a rural state, were surveyed via an internet survey tool as to their motivation for moonlighting, perceived educational effects--positive or negative--and its role in practice selection. RESULTS: Seventy-eight percent of respondents reported that they participated in moonlighting. Supplementation of income was the most commonly reported motivation (identified by 95.4 percent of respondents), followed closely by acquisition of additional clinical experience (87 percent). The majority perceived moonlighting as overall beneficial to residency program education (91.1 percent), beneficial in preparation for clinical practice (98.5 percent), and having a role in selection of future practice (89 percent). CONCLUSIONS: Practicing Midwestern family physicians perceive an important role for moonlighting in residents' clinical educational experiences and practice selection. PMID- 26380430 TI - Review of Acute Coronary Syndromes: Diagnosis and Management of ST-Elevation Myocardial Infarction. AB - Acute coronary syndrome is a life-threatening event that affects millions of people each year and accounts for a big portion of hospital visits. With an ever growing elderly patient population, ischemic heart disease is more prevalent than ever before. It is paramount that physicians of all fields are cognizant of the various presentations of acute coronary syndrome (ACS), as its prompt diagnosis and treatment profoundly decreases mortality and morbidity. Under the American College of Cardiology Foundation and the American Heart Association, guidelines are published for the optimal management of patients with acute coronary syndromes. Guidelines are continuously evolving as more multicenter randomized trials, new medications and new technologies continue to change the way we treat acute coronary syndromes. The focus of this review is ST-elevation myocardial infarction and it provides answers to some of the fundamental questions through evidence-based guidelines. PMID- 26380431 TI - Methods for Benefit and Risk Assessment of Drugs. PMID- 26380432 TI - Extenuating Circumstances: Smoking--A Deadly Addiction. PMID- 26380433 TI - Quality Focus: Improving Health with Immunizations. PMID- 26380434 TI - DAKOTACARE Update: Healthcare Quality. Part 3: Cancer Screenings. PMID- 26380435 TI - Patient Education: Blessing and Curse of Alcohol. PMID- 26380436 TI - [Vegetarian Diet and Cardiovascular Health--a Speech at the 12th National Academic Conference of Integrative Medicine on Cardiovascular Disease by Academician]. PMID- 26380437 TI - [Protection and Mechanism of Qingyuan Shenghua Decoction on Multiple Organs of Sepsis Patients after Bone Trauma]. AB - OBJECTIVE: To observe the protection of Qingyuan Shenghua Decoction (QSD) on multiple organs of sepsis patients after bone trauma, and to preliminarily explore its mechanism. METHODS: Totally 60 sepsis patients after bone trauma were randomly assigned to the treatment group and the control group according to random digit table, 30 in each group. All patients received routine Western medical treatment. Patients in the treatment group additionally took QSD or were nasally fed with QSD, one dose per day for 1 week. Changes of WBC, oxygenation index (PaO2/FiO2), serum creatinine (SCr), total bilirubin (TBIL), aspartate aminotransferase (AST), fibrinogen (FIB), D-dimer (DD), activated partial thromboplastin time (APTT), pro-calcitonin (PCT), C-reactive protein (CRP), heart rate (HR), mean arterial pressure (MAP), intra-abdominal pressure, scores for Acute Physiology and Chronic Health Evaluation II (APACHE II), sequential organ failure assessment (SOFA) scores were observed before treatment and on day 1, 3 and 7 after treatment. RESULTS: Compared with the control group at the same time point, MAP increased at post-treatment day 1 and 3; CRP, APTT, HR, SCr, TBIL, AST, intra-abdominal pressure at post-treatment day 3 obviously decreased in the treatment group (P < 0.05, P < 0.01). WBC, SOFA scores, PCT, CRP, APACHE II, APTT, D-D, HR, SCr, TBIL, AST and intra-abdominal pressure significantly decreased; FIB, MAP and PaO2/FiO2 obviously increased at post-treatment day 7 (P < 0.05, P < 0.01). CONCLUSION: QSD had good protective effect on multiple organ function in sepsis patients after bone trauma, and its mechanism might be related with effectively clearing endotoxin, alleviating inflammatory reactions, and fighting against coagulation dysfunction. PMID- 26380438 TI - [Effect of Acupuncture on Prognosis and Immune Function of Sepsis Patients]. AB - OBJECTIVE: To study the effect of acupuncture on the immune function of sepsis patients. METHODS: Ninety sepsis patients were assigned to the control group, the thymosin a1 group, and the acupuncture treatment group according to random digit table, 30 patients in each group. Patients in the control group were treated according to the guideline of Surviving Sepsis Campaign (SSC). Patients in the control group received routine treatment. Those in the thymosin alpha1 group additionally received subdermal injection of thymosin alpha1 (1.6 mg), once per day for 6 successive days. Needling at related points such as Zusanli (ST36), Yanglingquan (GB34), Neiguan (PC6), Guanyuan (RN4), and so on, was performed in patients of the acupuncture treatment group, once per day for 6 successive days. T cell subgroups (CD3+, CD4+, CD8+, CD4+ /CD8+) and immunoglobulin levels (IgG, IgA, IgM) were detected. The length of ICU hospital stay, hospital readmission rate, and 28-day mortality were compared among the three groups. RESULTS: After six days of treatment, CD3+, CD4+, CD8+, IgG, IgA, IgM, and CD4+ /CD8+ ratio of three groups were all significantly increased (P < 0.01). Of them, CD3+, CD4+, CD8+, IgG, IgA, and IgM increased more significantly in the thymosin alpha1 group and the acupuncture treatment group (P < 0.01). Compared with the control group, the ICU hospitalization length was significantly shortened, the hospital readmission rate and the 28-day mortality were lower in the thymosin alpha1 group and the acupuncture treatment group (P < 0.05, P < 0.01). There was no statistical difference in each index between the thymosin alpha1 group and the acupuncture treatment group (P > 0.05). CONCLUSION: Acupuncture could adjust the immune function of sepsis patients, improve their immunological indicators and prognoses. PMID- 26380439 TI - [Effect of Compound Tongfu Granule on Intestinal Permeability in Elderly Sepsis Patients]. AB - OBJECTIVE: To explore the effect of Compound Tongtu Granule (CTG) on intestinal permeability in elderly sepsis patients. METHODS: Eighty elderly sepsis patients were randomly assigned to the experimental group and the control group by randomized double blinded method, 40 in each group. On the basis of conventional antiseptic treatment program, patients in the experimental group took CTG, while those in the control group took placebos. The dosage for CTG or placebos was 14.3 g each package, one package each time, twice daily for 14 successive days. Patients' abdominal symptoms and signs, levels of serum inflammatory factors (high-sensitivity C-reactive protein and procalcitonin), levels of plasma endotoxin, and the intestinal permeability (IP, represented by urinary lactulose/mannitol excretion rate) were compared between the two groups before and after treatment. RESULTS: After 14-day treatment, patients in the experimental group had improved abdominal symptoms, increased frequency of defecation, significantly decreased levels of plasma endotoxin and IP, when compared with the control group (P < 0.05). CONCLUSION: CTG could improve the intestinal barrier function in elderly sepsis patients. PMID- 26380440 TI - [Treatment of Sepsis-associated Encephalopathy by Xingnaojing Injection: a Clinical Observation]. AB - OBJECTIVE: To observe the efficacy of Xingnaojing Injection (XI) in treatment of sepsis-associated encephalopathy (SAE). METHODS: Totally 65 SAE patients were retrospectively analyzed at EICU from September 2010 to September 2013. They were assigned to the control group (32 cases) and the treatment group (33 cases) according to whether they received XI. Patients in the control group received anti-infection and symptomatic support, while those in the treatment group were intravenously injected with XI at 20 mL per day for additional 7-10 days. The fever clearance time, Glasgow coma scale (GCS), C-reactive protein (CRP), neuron specific enolase (NSE), and improvement of electroen-cephalogram (EEG) were observed in the two groups. RESULTS: Compared with the control group, the fever clearance time was shortened, CRP levels decreased, GCS score and efficacy of EEG was alleviated in the treatment group after treatment with statistical difference (P < 0.05). No adverse reaction occurred during medication. CONCLUSION: X1 was safe and effective in treatment of SAE. PMID- 26380441 TI - [Treatment of Chronic Heart Failure Patients with Qi-Yang Deficiency and Blood Stasis Resistance Syndrome by Xnmallong Injection: a Multi-center Randomized Control Study]. AB - OBJECTIVE: To evaluate the efficacy and safety of Xinmailong Injection (XI) in treatment of chronic heart failure (CHF) patients with qi-yang deficiency and blood stasis resistance syndrome (QY-DBSRS). METHODS: Totally 238 CHF patients with QYDBSRS were assigned to the treatment group (118 cases) and the control group (120 cases) by randomized, double-blind, placebo parallel controlled method. Patients in the treatment group received routine therapy and XI (100 mg/2 mL, by dripping at 5 mg/kg, twice per day for 5 consecutive days), while those in the control group received routine therapy and XI mimetic agent (100 mg/2 mL, by dripping at 5 mg/kg, twice per day for 5 consecutive days). The heart function classification of New York Heart Association (NYHA), 6-min walking distance, left ventricular ejection fraction (LVEF), scores for Chinese medical symptoms were observed before and after treatment, and safety assessed. RESULTS: Totally 235 patients actually entered full analysis set (FAS), including 120 cases in the control group and 115 cases in the treatment group. The total effective rate of heart function, 6-min walking distance and increased post-pre-treatment distance in the experimental group were superior to those of the control group with statistical difference (all P < 0.05). Compared with the control group, increased value of post-pre-treatment LVEF, the total effective rate of Chinese medical syndrome efficacy, scores for Chinese medical symptoms and decreased post-pre treatment value of Chinese medical syndrome scores were obviously improved (all P < 0.05). There was no significant difference in the incidence of adverse events between the two groups (P > 0.05). CONCLUSIONS: XI could improve the heart function of CHF patients, improve Chinese medical symptoms, elevate exercise tolerance, and improve LVEF. It had no obvious toxic and side effects. PMID- 26380442 TI - [Treatment of Level 2 Hypertension by Diagnosis and Treatment Program of Integrative Medicine: a Multi-centre, Randomized Controlled Trial]. AB - OBJECTIVE: To explore the therapeutic effect of diagnosis and treatment program of integrative medicine (IM) on level 2 hypertension in the young and middle-aged patients and their ambulatory blood pressure. METHODS: A randomized, placebo parallel and controlled, multi-center clinical trial was performed. Totally 199 young and middle-aged level 2 hypertension patients were randomly assigned to the treatment group (99 cases) and the control group (100 cases). All received combined hypotensive treatment program by taking Nifedipine Sustained Release Tablet and Hydrochlorothiazide as basic drugs. Patients in the treatment group additionally took Western medicine (WM) combined Jiangyabao serial drugs (0.31 g per tablet, 2 tablets each time, twice daily), while those in the control group additionally took WM combined simulative agents of Jiangyabao serial drugs (0.31 g per tablet, 2 tablets each time, twice daily). The treatment course was 8 weeks for all, and 24-week follow-ups performed. 24 h ambulatory blood pressure and casual blood pressure, and their efficacies were compared between the two groups, and safety assessed as well. RESULTS: Compared with before treatment in the same group, daytime and night casual blood pressure, as well as 24 h ambulatory blood pressure were all obviously improved in the two groups (P < 0.01). Average diastolic and systolic blood pressures at night decreased more in the treatment group than in the control group with statistical difference (P < 0.05). There was no statistical difference in total efficacies of daytime casual blood pressure or ambulatory blood pressure (P > 0.05). CONCLUSION: Jiangyabao serial drugs combined WM in treating young and middle-aged level 2 hypertension patients showed obvious effect in improving night blood pressure, especially for night diastolic blood pressure. PMID- 26380443 TI - [Development and Evaluation of GS-SF for Gastric Stuffiness (Wei PI) Patients Based on Item Response Theory, Computerized Adaptive Testing, and Data Simiuation]. AB - OBJECTIVE: To develop and evaluate the short version of patient reported outcomes (PROs) questionnaire for gastric stuffiness (Wei Pi) patients with modern test theory and technologies, hoping to provide testing tools for related clinical practice and scientific researches with higher quality and less administrative and response burdens. METHODS: Using descriptive study design, clinical data were collected with sociological questionnaire and previous developed full items version of PROs instrument for gastric stuffiness (Wei Pi) patients via field and online surveys between Sep 2011 and Mar 2012. The statistical analysis group identified the termination parameters firstly, and then selected items with discrimination, fitting residual, item information curve (IIC) , item characteristic curve (ICC), and the rank of computerized adaptive testing (CAT) select proportion, etc. After assumption evaluation of item response theory (IRT), IIC, ICC, difficulty coefficient distribution, items-response relation and thresholds, etc. were used for psychometric evaluation of instrument. RESULTS: A total of 331 patients [Ages: 31.99 +/- 10.29 yrs; Male: 186 (56.3%)] were enrolled in statistical analysis. The test termination criterion was Max SE = 0.2 or Max items number =16. After items selection, a 15-item short version of instrument, which contains symptoms facet (8 items) and impact facet (7 items) was generated. With good unidimensionality, local independence, and monotonicity, the IC and ICC in IRT analysis showed good working capability of the questionnaire. The difficulty coefficient distribution and items-response relation were also rational, as well as response thresholds. CONCLUSIONS: The short version of PROs instrument for adult gastric stuffiness (Wei Pi) patients was successfully developed and assessed. The instrument with good methodological and reporting quality could be used in clinical and scientific evaluating their symptoms and impact. PMID- 26380444 TI - [Treatment of Recurrent Oral Ulceration (Yin Deficiency Fire Excess Type) by Qianjin Kouchuang Jiawei Granule: a Clinical Observation]. AB - OBJECTIVE: To observe the curative effect of Qianjin Kouchuang Jiawei Granule (QKJG) on recurrent oral ulceration [yin deficiency fire excess type (YDFET)]. METHODS: Totally 120 patients who suffered from recurrent oral ulceration (YDFET) were randomly assigned to two groups, the experiment group and the control group, 60 in each group. Patients in the experiment group took QKJG, 20 g each time, twice per day, while those in the control group took Kouyanqing Granule (KG) , 20 g each time, twice per day. Fourteen days consisted of one therapeutic course, two for all. Scores for patients' symptoms and signs (ulcer area, exudation, hyperaemia, edema, the number of ulceration, burning sensation, and pain degrees) were assessed before treatment, at day 3 and 7 after treatment. Short-term efficacy was assessed by visual analogue scale (VAS). The total paralysis time and the total number of ulceration at month 12 after treatment were taken as judgment for long-term efficacy. Results Compared with before treatment in the same group, symptoms and signs were obviously improved at day 3 and 7 after treatment in the two groups (P < 0.05). Compared with the control group at day 3 after treatment, the improvement of edema, exudation, pain degree, and burning sensation was more obvious in the experiment group (P < 0.05, P < 0.01). The improvement of edema, pain degree, and burning sensation at day 7 after treatment was more obvious in the experiment group than in the control group (P < 0.05). As for short-term efficacy, the total effective rate was 86.67% (52/60 cases) in the experiment group and 83.33% (50/60 cases) in the control group, with no statistical difference between the two groups (P > 0.05). As for long-term efficacy, the total effective rate was 90.00% (54/60 cases) in the experiment group, significantly higher than that of the control group with statistical difference [81.67% (49/60 cases), P < 0.05]. At month 12 after treatment, the total number of ulceration was reduced and the paralysis time of ulcer attack prolonged in the experiment group, with statistical difference when compared with the control group (P < 0.05). CONCLUSION: QKJG showed better long-term efficacy than that of KG in treating recurrent oral ulceration (YDFET). PMID- 26380445 TI - [Treatment of Epidermal Growth Factor Receptor Inhibitors Associated Adverse Skin Reactions by Zhiyang Pingfu Liquid: a Clinical Study]. AB - OBJECTIVE: To study the curative effect of Zhiyang Pingfu Liquid (ZPL) in treating epidermal growth factor receptor inhibitors (EGFRIs) associated adverse reactions of the skin. METHODS: All 54 patients with pathologically confirmed malignant tumor had EGFRIs induced adverse reactions of the skin to various degrees. ZPL was externally applied for them all, once or twice per day, 14 days consisting of one therapeutic course. Changes of adverse skin reactions, time for symptoms relief, adverse skin reaction types suitable for ZPL were observed before and after treatment. RESULTS: EGFRIs associated skin adverse reactions were improved to various degrees after they used ZPL. The shortest symptoms relief time was 1 day while the longest was 12 days, with an average of 6.93 days and the median time 7 days. Compared with before treatment, itching, rash/scaling, acne/acneform eruptions were obviously improved (P < 0.05). CONCLUSION: ZPL could alleviate EGFRls associated adverse skin reactions, especially showed better effect on itching, rash/scaling, acne/acneform eruptions. PMID- 26380446 TI - [Investigation of Evolution Rules of Phlegm and Blood Stasis Syndrome in Hyperlipidemia and Ath- erosclerosis by NMR-based Metabolic Profiling and Metabonomic Approaches]. AB - OBJECTIVE: To explore evolution rules of phlegm and blood stasis syndrome ( PBSS) in hyperlipidemia and atherosclerosis (AS) using NMR-based metabolic profiling and metabonomic approaches based on formulas corresponding to syndrome. METHODS: Totally 150 SD rats were divided into the normal group, the model group, the Erchen Decoction (ED) group, the Xuefu Zhuyu Decoction (XZD) group, the Lipitor group, 30 in each group. The hyperlipidemia and AS rat model was duplicated by suturing carotid artery, injecting vitamin D3, and feeding with high fat diet. ED and XZD were used as drug probes. Blood samples were withdrawn at week 2, 4, and 8 after modeling. Blood lipids, blood rheology, histopathology and metabolomics were detected and analyzed. Results Results of blood lipids and pathology showed hyperlipidemia and early AS rat models were successfully established. At week 2 after modeling, levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) significantly increased, which reached the peak at week 4 and maintained at higher levels at week 8. ED exerted obvious effect in improving TC and LDL-C levels of early models, while XZD could greatly improve levels of TC and LDL-C of late models. Rheological results showed at week 2, there was no significant difference in whole blood viscosity, plasma viscosity, or hematocrit between the model group and the normal group (P > 0.05). At week 4 partial hemorheological indicators (such as plasma viscosity) were abnormal. Till week 8 whole blood viscosity, plasma viscosity, and hematocrit were significantly abnormal (P <0. 05, P < 0.01). As time went by, whole blood viscosity, plasma viscosity, and hematocrit showed gradual increasing tendency in the ED group, while they showed gradual decreasing tendency in the XZD group. Results of metabonomics showed significant difference in spectra of metabolites between the normal group and the model group. As modeling time was prolonged, contents of acetyl glucoprotein and glucose in the model group increased in late stage, which was in. line with results of blood lipids and hemorheology. ED showed more obvious effect in early and mid-term modeling (at week 2 and 4), and increased contents of partial metabolites (such as choline, phosphatidyl choline, glycerophosphocholine), but these changes in the XZD group were consistent with those of the model group. In late modeling (at week 8) XZD showed more obvious effect in improving contents of lactic acid, acetyl glycoprotein, LDL, creatine, choline, and glucose. CONCLUSIONS: ED and XZD not only showed regulatory effects on lipid disorders, but also could improve dysbolism of Chos. In formulas corresponding to syndrome, damp-phlegm was main pathogenesis of hyperlipidema and AS in early and mid stages. Blood stasis syndrome began to occur along with it progressed. Phlegm can result in blood stasis and intermingles with stasis. Phlegm turbidity runs through the whole process. PMID- 26380447 TI - [Changes of HPAA in Different Rat Models of Gan Stagnation, Pi Deficiency, Gan Stagnation Pi Defi- ciency and Interventional Effect of Chaishu Sijun Decoction]. AB - OBJECTIVE: To compare changes of hypothalamus-pituitary-adrenal axis (HPAA) in different rat models of Gan stagnation (GS), Pi deficiency (PD), Gan stagnation Pi deficiency (GSPD) syndromes, and to observe interventional effect of Chaishu Sijun Decoction (CSD, capable of soothing Gan-qi invigorating Pi) on them. METHODS: Seventy Wistar rats were divided into the normal control group (group 1), the GS group (group 2), the PD group (group 3), the GSPD group (group 4), the GS intervention group (group 5), the PD intervention group (group 6), and the GSPD intervention group (group 7) according to random digit table, 10 in each group. Rats in group 1 received no treatment. Rats in group 2 and 5 were modeled by chronic restraint method. Rats in group 3 and 6 were modeled by excess fatigue plus alimentary abstinence method. Rats in group 4 and 7 were modeled by chronic restraint, excess fatigue, and alimentary abstinence method. At the 2nd weekend of modeling, CSD at 2.86 g/kg was fed to rats in group 5, 6, and 7 by gastrogavage for 2 successive weeks. Equal volume of distilled water was given to rats in the rest 4 groups. On the 29th day, rats were killed, adrenal weight weighed, and adrenal index calculated. Levels of plasma and hypothalamus corticotropin-releasing hormone (CRH), plasma and pituitary adrenocorticotrophic hormone (ACTH), and plasma corticosterone (CORT) were determined using radioimmunity. RESULTS: Compared with group 1, adrenal index significantly decreased in group 2, 3, and 4 (P < 0.05). Of them, plasma and hypothalamus CRH, plasma CORT increased significantly in group 2 and 4 (P < 0.05). Besides, plasma and pituitary ACTH increased in group 4 (P < 0.05). Plasma and pituitary ACTH, as well as plasma CORT decreased significantly in group 3 (P < 0.05). Compared with group 2, 3, and 4, adrenal index increased significantly in group 5, 6, and 7 (P < 0.05). Compared with group 2, plasma CORT, hypothalamus CRH, and pituitary ACTH decreased significantly in group 5 (P < 0.05). Compared with group 3, plasma ACTH and CORT increased significantly in group 6 (P < 0.05). Compared with group 4, plasma CRH, ACTH, CORT, hypothalamus CRH, and pituitary ACTH decreased in group 7 (P < 0.05). CONCLUSIONS: The function of HPA .axis was damaged to varying degrees in rats of the three models in this experiment. Hyperactivity of HPA axis existed in GS syndrome and GSPD syndrome. Impairment of feedback regulation in hypothalamus and pituitary was accompanied in GSPD syndrome. Hypofunction of HPA axis existed in PDS. CSD, capable of soothing Gan-qi invigorating'Pi, showed improvement on disarranged HPAA, but with optimal effect on GSPD syndrome. CSD had higher correlation with GSPD syndrome. PMID- 26380448 TI - [Icariin Promoted Osteogenic Differentiation of SD Rat Bone Marrow Mesenchymal Stem Cells: an Experimental Study]. AB - OBJECTIVE: To observe features of Icariin in promoting osteogenic differentiation of SD rat bone marrow mesenchymal stem cells (BMSCs) in vitro. METHODS: (1) SD rats' BMSCs were isolated and purified by mechanically isolated and cultured by whole bone marrow adherent method. Effects of various concentrations Icariin on serum activities of alkaline phosphatase (ALP) were detected using amino antipyrine phenol determination method at day 3, 6, 9, 12, 15, 18, and 21. Calcium nodes of each groups were detected using alizarin red staining. Roles of various concentrations Icariin in promoting osteogenic differentiation of BMSCs were observed. (2) BMSCs were divided into the blank control group, the osteogenic induced group, and the Icariin group (0.5 microg/mL). ALP activities were detected at day 7, 14, and 21 of culture. Meanwhile, ALP positive staining rate and calcium nodes were detected at day 14 and 21 respectively. Additionally, mRNA expressions of Runt-related transcription factor-2 (Runx2) and Osteocalcin were detected at day 7, 14, and 21 by real-time fluorescent quantitative PCR. RESULTS: (1) 0.05-5.0 microg/mL Icariin could significantly elevate serum ALP activities. Of them, 0.2-2.0 microg/mL Icariin significantly increased calcium nodes numbers (P < 0.01). (2) When Icariin promoted osteogenic differentiation of BMSCs, Runx2 mRNA expression levels and ALP activities increased earlier and then decreased, while osteocalcin mRNA expression levels continued to increase (P < 0.01). Compared with the osteogenic induced group, ALP activities and ALP positive staining rate were both elevated after 14 days of Icariin treatment in the Icariin group (P < 0.05, P < 0.01). CONCLUSIONS: Icariin could promote the differentiation of BMSCs to osteoblasts by up-regulating Runx2 mRNA expression levels. It also could promote the mineralization by increasing ALP secretion and Osteocalcin mRNA expression levels, thereby promoting mature of newly generated osteoblasts. PMID- 26380449 TI - [Effective Ingredients of Yangjing Zhongyu Decoction Regulated Androgen Biosyntheses by Mitogen-Activated Protein Kinase Pathway in Porcine Granulose Cells]. AB - OBJECTIVE: To study the molecular mechanism of Yangjing Zhongyu Decoction (YZD) n butanol extracts (ZDC) and ethyl acetate extracts (YSYZ) in reducing androgen in porcine granulose cells by mitogen-activated protein kinase (MAPK) pathway. METHODS: Porcine granulose cells were isolated and cultured. They were inoculated by MAPK inhibitor PD98059 at different concentrations, and then they were divided into the blank control group (0), 1, 3, 10, and 25 micromol/L groups. After 24-h culture the cytochrome P450c17a (CYP17) mRNA expression level was detected using Real-time fluorescent quantitative PCR. Contents of androgen (testosterone) in the supernate were detected using RIA and optimal PD98059 concentration screened. After intervened by 10 micromol/L PD98059 for 24 h, the culture solution was intervened by effective ingredients of with or without YZD or YSYZ at various concentrations (0, 1 , 5, 25, 50 mg/mL) at various time points (3, 6, 18, 24 h). Expression levels of p-ERK1/2, c-Fos and CYP17 were detected by Western blot. Testosterone content in the supernate was determined by radioimmunoassay (RIA). RESULTS: Ten pLmol/L PD98059 could obviously decrease p-ERK1/2 protein expression and increase CYP17 mRMA expression, and elevate testosterone content in the supernate (P < 0.05). ZDC and YSYZ at 25 ng/mL could increase p-ERK1/2 protein expression and c-Fos levels, and reduce CYP17 protein expression, and lower testosterone content in the supernate after 6-h intervention (P < 0.01). CONCLUSION: Effective ingredients of YZD could reduce androgen production in porcine granulose cells through increasing activities of MAPK. PMID- 26380450 TI - [Effects of Nourishing Yin Removing Fire Chinese Herbs on Gene Expression of Hypothalamic Ghrelin and its Receptor in Female Precocious Rats]. AB - OBJECTIVE: To observe the effect of nourishing yin removing fire Chinese herbs (NYRF-CH) on the gene expression of hypothalamic growth hormone secretion peptide (Ghrelin) and its receptor growth hormone secretion peptide receptor 1alpha (GHSR1-alpha) at the puberty onset of danazol induced female precocious rats. METHODS: Forty female SD rats were randomly divided into 4 groups, i.e., the normal group (N), the model group (M), the normal saline intervention group (NS), and the NYRFCH intervention group (NI), 10 in each group. 300 microg danazol was subcutaneously injected to all rats except those in the N group to prepare precocious rat model. NYRFCH and normal saline was respectively administered to rats in the NI and the NS group from the 15th day old for 7-10 days. No treatment was given to rats in the N group. Time of rats' vulva opening was recorded. Ovary index and uterus index were calculated. Peripheral blood levels of estradiol (E2), follicle stimulating hormone (FSH), and luteinizing hormone (LH), and hypothalamic contents of gonadotropin releasing hormone (GnRH) as well as the gene expression of hypothalamic Ghrelin and GHSR1-alpha were determined. Results Compared with the N group, the vulva opening time was advanced in the model group; peripheral blood levels of E2 and LH, uterus index, hypothalamic contents of GnRH increased; peripheral blood FSH levels and mRNA levels of hypothalamic Ghrelin and GHSR1-alpha decreased (P < 0.05, P < 0.01). Compared with the M group and the NS group, the vulva opening time was not advanced in the NI group; peripheral blood levels of E2 and LH, uterus index and hypothalamic contents of GnRH obviously decreased (P < 0.05, P < 0.01); mRNA levels of hypothalamic Ghrelin and GHSR1-alpha increased (all P < 0.01). But there was no statistical difference in the hypothalamic contents of Ghrelin, or the number and activity of GHSR1-alpha (P > 0.05). CONCLUSION: NYRFCH had regulatory effect on regulating hypothalamic Ghrelin and GHSR1-alpha at gene transcription levels. PMID- 26380451 TI - [Treatment of Chemotherapy Related Leukocytopenia by Oral Administration of Multiple Leucogenic Drugs Combined with G-CSF: an Experimental Study]. AB - OBJECTIVE: To evaluate efficacies of three commonly used oral drugs including Berbamine Hydrochloride Tablet (B), Qijiao Shengbai Capsule (Q), and Leucogen Tablet (L) (by single drug, two drugs or three drugs) combined with granulocyte colony-stimulating factor (G-CSF) for treat ment of chemotherapy related leukocytopenia in mice. METHODS: Totally 156 Kunming male mice were divided into the normal control group (A, n=24), the model group (B, n=24), the G-CSF group (C, n =24), the G-CSF+Q group (D, n=12), G-CSF+ B (E, n=12), the G-CSF+L group (F, n=12), the G-CSF + Q + B group (G, n=12), the G-CSF + Q + L group (H, n=12), the G-CSF + L + B group (I, n=12), and the G-CSF + L + Q + B (J, n=12). Mouse models of chemotherapy related leukocytopenia were established by intraperitoneal injection of cyclophosphamide (CTX). A G-CSF group was set up as a positive control. Mice were treated by a single oral drug, a single oral drug combined with G-CSF, and two or three drugs combined with G-CSF respectively, and the death rate calculated. Hemocytes [such as white blood cells (WBC) and its classification, red blood cells (RBC), platelet (PLT), hemoglobin (Hb)] were calculated by hematology analyzer. Mice were anatomized and important organs weighed. Organ indices were calculated. RESULTS: There was no statistical difference in the mortality rate among all groups (P > 0.05). Compared with Group B, WBC was elevated in all other groups (P < 0.01). WBC and PLT were elevated most in Group J, Hb and RBC were also increased at the same time (P < 0.05, P < 0. 01). Compared with Group B, RBC increased in Group E, F, G, I, and J (P < 0.01); Hb obviously increased in Group C, E, F, H, I, and J (P<0.01). Compared with Group B and D, the promotion of erythroid hematopoiesis by G-CSF could be elevated in any group contained drug B and L (P < 0.05, P < 0.01). The spleen index of model mice could be significantly improved in Group C, D, and G (P < 0.01). The thymus index of model mice could be significantly improved in Group H (P < 0.05). CONCLUSIONS: The best scheme to treat mice with chemotherapy related leukopenia or decreased three blood series was to administrate three commonly oral drugs combined with G-CSF. Authors speculated that G-CSF and Q might have a certain effect on CTX induced immune inhibition. PMID- 26380452 TI - [Mechanism of Polypeptide Extract from Scorpion Venom Combined Rapamycin in Enhancing Autophagy of H22 Hepatoma Cells: an Experimental Study]. AB - OBJECTIVE: To observe enhanced effects of polypeptide extract from scorpion venom (PESV) combined Rapamycin on autophagy of H22 hepatoma cells in mice and to explore its possible mechanism. METHODS: The H22 hepatocarcinoma cell suspension was subcutaneously inoculated into 40 Kunming mice. Then tumor-bearing mice were randomly divided into four groups, i.e., the control group,the high dose PESV group, the low dose PESV group, and the combination group (high dose PESV + Rapamycin), 10 in each group. Mice in high and dose PESV groups were administered with 20 mg/kg and 10 mg/kg PESV respectively by gastrogavage. Mice in the combination group were administered with 2 mg/kg rapamycin and 20 mg/kg PESV by gastrogavage. The intervention lasted for 14 successive days. The tumor volume was measured once every other day, the tumor growth curve was drawn, and then the tumor inhibitory rate calculated. Pathological changes of the tumor tissue were observed by HE staining. Protein expression levels of mammal target of rapamycin (mTOR), UNC-51-like kinase-1 (ULK1), microtubule-associated protein1 light chain3 (MAPILC3A), and Beclin1 were detected by immunohistochemical assay. RESULTS: The growth of H22 hepatoma transplantation tumor was inhibited in high and low dose PESV groups and the combination group (P < 0.05). And there was statistical difference in tumor weight and tumor volume between the combination group and high and low dose PESV groups (P < 0.05). There was no statistical difference in tumor weight or tumor volume between the high dose PESV group and the low dose PESV group (P > 0.05). lmmunohistochemical assay showed that the protein expression of mTOR was higher, but protein expressions of ULK1, MAP1LC3A, Beclin1 were lower in the control group than in the rest 3 groups (P < 0.05, P < 0.01). Compared with the high dose PESV group, protein expressions of ULK1, MAP1LC3A, and Beclin1 were obviously lower (P < 0.05). CONCLUSION: PESV combined Rapamycin might inhibit the development of H22 hepatoma transplantation tumor in mice possibly through inhibiting the activity of mTOR, enhancing expressions of ULK1, MAP1LC3A, and Beclin1. PMID- 26380453 TI - [Effects of Salvianolate on Myosin Heavy Chain in Cardiomyocytes of Congestive Heart Failure Rats]. AB - OBJECTIVE: To explore the effect of Salvianolate on myosin heavy chain (MHC) in cardiomyocytes of congestive heart failure (CHF) rats. METHODS: Sixty male SD rats were divided into 6 groups according to random digit table, i.e., the normal control group (NCG), the model group, the Captopril group (CAG), the low dose Salvianolate group (LSG), the high dose Salvianolate group (HSG), the Captopril and high dose Salvianolate group (CSG), 10 in each group. CHF rat model was established with peritoneal injection of adriamycin in all rats except those in the NCG. Equal volume of normal saline was peritoneally injected to rats in the NCG, once per week for 6 successive weeks. Corresponding medication was started from the 5th week of injecting adriamycin. Rats in the CAG were administered with Captopril solution at the daily dose of 10 mg/kg by gastrogavage. Rats in the LSG and the HSG were administered with Salvianolate solution at the daily dose of 24.219 mg/kg and 48.438 mg/kg respectively by gastrogavage. Salvianolate was dissolved in 2 mL 5% glucose solution and administered by peritoneal injection. Rats in the CSG were peritoneally injected with high dose Salvianolate solution and administered with Captopril solution by gastrogavage. Two mL normal saline was peritoneally injected to rats in the model group, once per day for 8 successive weeks. Eight weeks later, the cardiac function and myocardial hypertrophy indices were detected by biological signal collecting and processing system. mRNA expression levels of alpha-MHC and beta-MHC in cardiac muscle were detected by fluorescence quantitative PCR. Expressions of protein kinase C (PKC) in cardiac muscle were detected by Western blot. RESULTS: Compared with the normal control group, heart mass index (HMI) and left ventricular mass index (LVMI) obviously increased in the model group (P < 0.01). Compared with the model group, HMI and LVMI decreased in HSG, CAG, and CSG groups (P < 0.05, P < 0.01). It was more obviously lowered in the CSG group than in the CAG group (P < 0.05). Compared with the NCG, the mRNA expression level of alpha-MHC in cardiac muscle decreased, the mRNA expression level of p-MHC and the expression of PKC in cardiac muscle increased in the model group (P < 0.01). Compared with the model group, the mRNA expression level of alpha-MHC in cardiac muscle was increased, and the mRNA expression level of beta-MHC and the expression of PKC in cardiac muscle were decreased in HSG, CAG, and CSG groups (P < 0.05, P < 0.01). There was statistical difference between the CSG group and the CAG group (P < 0.05). CONCLUSIONS: Salvianolate could up-regulate the mRNA expression level of alpha MHC, and down-regulate the mRNA expression level of beta-MHC in cardiac muscle. Its mechanism might be related to decreasing the expression of PKC. PMID- 26380454 TI - [English Translation Study on Culture-loaded Words in Shanghanlun under Culture Translation Theory]. PMID- 26380455 TI - [Thinking on the Relationship of Formulas Corresponding to Diseases in Chinese Medicine]. AB - "Treatment based on diseases identification and formulas corresponding to diseases" is one of important therapy modes of Chinese medicine. Although it originates from Huangdi Neijing, it is seldom systematically discussed. Modern Chinese medicine (CM) now faces diseases mostly with comparatively confirmed Western medical diagnoses. Most of them have specific pathophysiological changes. How to interpret these specific pathophysiological changes, play CM's advantages, and improve clinical efficacies has become an inevitable problem for modern CM in clinic. Authors expounded historic development and clinical application of "formulas corresponding to diseases", and its difference from "formulas corresponding to syndromes", put forward that we should combine "formulas corresponding to diseases" and "formulas corresponding to syndromes" in CM clinics. We should focus on the disease and summarize treatment rules, thereby improving targeted CM formulas. PMID- 26380456 TI - [Strategies and Progress of Chinese Medicine in Reversing Tumor Multidrug Resistance]. PMID- 26380457 TI - [Placement of metal clips as a means for identifying the tumor bed in women post lumpectomy]. AB - INTRODUCTION: Surgical clips inserted during breast-conserving surgery [BCS] serve as a surrogate of the lumpectomy cavity. Visualization of the surgical clips by imaging prior to radiotherapy (RT), during treatment planning, aids in designing the treatment volume for breast irradiation. OBJECTIVES: The aim of this study was to evaluate whether there is a distinct difference in the tendency to insert a metal clip during BCS, that is related to the hospital where the procedure was performed and to evaluate whether there are differences in the boost planning treatment volume (PTV). METHODS: This is a retrospective study. The records of all patients treated by adjuvant RT after BCS were reviewed. Boost PTV was calculated in cubic centimeters (ccj and compared between the groups. RESULTS: Of the 143 patients included in the study, 31% were operated on in private hospitals and 69% were operated on in public hospitals. A statistically significant difference was found in clip insertion in patients treated in private hospitals compared to public hospitals. No statistical differences were found in the boost PTV size between the groups (p = 0.448). A similar difference was found when comparing tertiary public centers to smaller secondary public centers. CONCLUSION: Our study demonstrates a higher tendency to insert metal clips during BCS in private hospitals as compared to public hospitals. There were no differences in the tumor bed PTV in patients with or without surgical clips. PMID- 26380458 TI - [Tuberculosis among patients in Israel with anti-TNF]. AB - Treatment with anti-TNF increases the rate of the reactivation of latent tuberculosis (TB) infection. We present five case reports of patients who were treated with anti-TNF and developed active TB infection. Physicians should be aware of this possible complication and should conduct screening with the purified protein derivative test (PPD) or the interferon gamma release assay (IGRA) before anti-TNF treatment. PMID- 26380459 TI - [Re-implantation of a mitraclip device in a patient with recurrent mitral regurgitation]. AB - Mitral regurgitation is a common disease in patients with cardiomyopathies, constituting poor prognosis when present. In patients with an increased risk for surgery, a minimally-invasive, percutaneous procedure currently exists, in the form of an edge-to-edge repair technique using the MitraClip device. This approach allows for great flexibility in specific situations, such as in the addition of another clip when necessary, either during the procedure or after a follow-up period. The following case study depicts the course of therapy for a patient with ischemic cardiomyopathy and severe bi-ventricular failure. The patient was implanted with a MitraClip device five months before the current event, and now presents with clinical deterioration, and a renewed mitral valve insufficiency. PMID- 26380460 TI - [Successful termination of ventricular fibrillation using the precordial thump]. AB - A 75 year old female underwent angiography which revealed diffuse restenosis in a bare metal stent implanted in the right coronary artery, three month earlier. A wire was used to cross the lesion; balloon angioplasty was performed followed by drug eluting stent implantation. Inflation times were short. As the balloon of the stent was retrieved, the patient went into ventricular fibrillation (VF). An order to charge the defibrillator for DC shock was given. The operating physician immediately delivered a quick strong blow to the patient's thorax (precordial thump) which stopped the VF rhythm and converted it into atrial fibrillation. The patient regained consciousness and had no recollection of what had happened. No DC shock was needed. PMID- 26380461 TI - [Of worms and men--Administration of helminth products as an innovative approach to treatment of autoimmune diseases]. AB - In areas where helminth infections are common, there is a low prevalence of autoimmune diseases. This observation gave rise to the hygiene hypothesis, claiming that certain organisms which were abundant in the human microenvironment hold an immunoregulatory and immunosuppressive effect, therefore, their eradication led to an increase in immune mediated diseases. This hypothesis laid the foundation for several directions of research which demonstrated an immunosuppressive and immunoregulatory effect of helminths on both the acquired and the innate immune systems. These studies led to the examination of the therapeutic potential of helminths and their components in treating different autoimmune diseases such as inflammatory bowel disease, rheumatoid arthritis, multiple sclerosis, and systemic lupus erythematosus. The administration of helminth products in murine models of these diseases exhibited a positive effect on disease expression, morbidity and mortality, as well as the ability to prevent the onset of disease to some extent (when given in a preventive protocol). Recently, a synthetic molecule composed of phosphorylcholine (a product of the nematode a. vitae) combined with the protein tuftsin, which is produced by human splenocytes, was shown to exert the aforementioned positive effects on a murine model of systemic lupus erythematosus (SLE). These discoveries point to a new direction in research for developing helminth-based therapies for autoimmune diseases. PMID- 26380462 TI - [Allegations of sexual misconduct against physicians and possible defence strategies]. AB - Allegations of sexual misconduct against physicians by patients, as well as their relatives, are becoming more prevalent recently. No physician is immuned against such allegations. However, several medical specialties are at an increased risk for such claims; among them are Obstetrics and Gynecology, Pediatrics, Psychiatry and Family Physicians. Such claims can also be forwarded by relatives or friends. The law that deals with sexual harassment is probably one of the most elusive and troublesome regulations. In the present review, the magnitude of the phenomenon, as well as preventive measures, including the use of a chaperone nurse, are discussed. PMID- 26380463 TI - [Atrial fibrillation ablation]. AB - Atrial fibrillation (AF) is the most commonly encountered arrhythmia. Atrial fibrillation has significant implications in terms of morbidity and effects on quality of life, especially due to the risk of embolic phenomena and in particular embolic stroke that may have significant prognostic implications. The prevalence of AF increases with age and in patients with cardiac disease. Atrial fibrillation ablation is becoming a viable option and the number of procedures is on the rise in suitable patients. In this review we describe the rationale behind this procedure in terms of underlying mechanisms of AF, various techniques and risks vs. benefits in different patient groups. Whether atrial fibrillation ablation, should be used as first line therapy is still controversial. In addition, it should be remembered that even after a presumably successful ablation, it is not an indication to stop anticoagulation therapy. Anticoagulation should be maintained if appropriate guideline indications exist. e PMID- 26380464 TI - [Pre-labor maternity leave for working women in physically demanding occupations]. AB - Pregnant women, when employed in physically demanding occupations, may encounter difficulties in carrying out their work throughout pregnancy. Many such "blue collar" workers are unable to proceed in strenuous work during advanced stages of pregnancy. However, scientific evidence is not sufficient to support the widely accepted assumption of health risks due to the hard work during pregnancy. Therefore, in Israel, as long as pregnancy is normal, and the good health of both the mother and fetus is maintained, such workers are not entitled to sick leave or any other form of compensation. Nevertheless, many agree that strenuous work is not suitable for pregnant women, as a medical survey partly demonstrates. Identification of this problem and review of relevant literature led to the formation of a committee by the Israeli National Council for Women's Health. We hereby summarize relevant literature, describe the committee's work and elaborate its recommendations, mainly to consider and establish a unique compensated pre birth leave for pregnant women whose work is physically strenuous. PMID- 26380465 TI - [Novel therapies for idiopathic pulmonary fibrosis]. AB - Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease of unknown cause. The clinical course is unpredictable, but the disease is usually progressive with a median survival of 2-5 years as a result of advanced respiratory failure. The current hypothesis of the disease mechanism is recurrent injury to the respiratory epithelium which leads to an uncontrolled wound healing process resulting in fibrosis rather than repair. Despite better understanding of the pathogenesis, there is no effective therapy for the disease. In this review, we present the positive results of recently published clinical trials regarding therapy for IPF, with emphasis on pirfenidone and nintedanib. PMID- 26380466 TI - [The development of the rehabilitation medicine concept in Israel (1948-1974)]. AB - The field of physical medicine and rehabilitation in Israel was developed in different ways. Some services were developed as a part of comprehensive rehabilitation centers like the Loewenstein Hospital and others were developed as a part of specific disciplines, like the Polio-Rehabilitation Center at Assaf Harofeh hospital. Moreover, the various fields of rehabilitation medicine were developed at different rates. The origin of each stemmed from different circumstances. Sometimes they were developed with a direct connection to a national event and sometimes separately. Occasionally, the field was developed as a result of one person's initiation and others as a result of the establishment's recognition of the value and the essentiality of the field. This essay will focus, in a chronological manner, on the development of the medical rehabilitation fields, that took place in the two leading rehabilitation centers in Israel, the Loewenstein Hospital and at Tel Hashomer. These rehabilitation centers were established in Israel close to the establishment of the State of Israel and their activity will be discussed until 1974, the year in which the Israeli society had to deal with the results of the Yom Kippur war, which had drastic implications on rehabilitation medicine. PMID- 26380467 TI - [Pregnancy in anorexia nervosa--an oxymoron that has become reality]. AB - In the last decade there has been a significant increase in the incidence of pregnancy in patients suffering from anorexia nervosa. This change is partly explained by the social processes that constitute a significant factor in the etiology of the disease. Yearning for thinness as representing the values of control and success has become a major cultural desire and this swept into a vortex of the disease many sexually active women at childbearing age, which was rare in anorexic patients in the past. Additionally, because amenorrhea is a common condition in anorexia nervosa, pregnancy during active disease seems to be an impossible oxymoron. While some patients succeed in conceiving spontaneously, fertility clinics provide an alternative solution for those who have difficulties conceiving. It seems that fertility professionals have little knowledge about anorexia nervosa and even when they diagnose it, the dilemma as to whether to refuse to treat these patients is not easy to solve. Pregnancy in anorectic patients during active disease puts the fetus at increased risk for complications during pregnancy and labor. Common complications are spontaneous abortion and growth retardation. One must take into consideration that underweight pregnant women require a professional eating disorders assessment and, if indeed it turns out that anorexia nervosa is active, it is necessary to refer her to an eating disorders clinic for treatment and to define the pregnancy as a pregnancy at risk. PMID- 26380468 TI - [DR. Hanka Weinberg-Heruti: the pediatrician from Merchavia--the first woman doctor 'Kibbutznik' in the Kibbutz Ha'artzi]. AB - Dr. Hanka Weinberg-Heruti, a pediatrician at the Ha'Emek Hospital and a member of Kibbutz Merchavia is regarded in the history of medicine in Eretz Israel as the first female physician in the Kibbutz Ha'Artzi movement-Hashomer Hatsa'ir, and one of the founders of children's medicine in the country. Dr. Weinberg-Heruti was able to break the accepted norms of the period and prove "you could be both a hospital doctor and a loyal kibbutz member". This was far from simple for there was an iron rule in that kibbutz movement: "Every member must perform physical labour to build the kibbutz and to work in its framework. This principle is inviolable nor can one deviate from the norm". Dr. Weinberg-Heruti dared to break that rule and prove that a successful combination of both her purposes in life was possible. Thus, the aim of the article is twofold: to survey her unique position as hospital doctor and faithful 'kibbutznik', who dared to break the "holy" principle at the ideological roots of kibbutz life--that it was unthinkable for a member to refrain from physical labour. Secondly, to illuminate her medical career as pediatrician in Ha'Emek Hospital, and describe the innovations she introduced to the children's ward, survey her groundbreaking research, that examined the influence of the Beit Shean Valley climate on infant development. Her conclusions dramatically affected the treatment and upbringing of children in that climate, and were adopted not only in local kibbutzim but throughout the country. PMID- 26380469 TI - [Thoughts on "fitness for detention"]. PMID- 26380470 TI - [21st European Society Pediatric Rheumatology Congress (PRES 2014)-- Belgrade, Serbia. 17th-21st September 2014]. PMID- 26380471 TI - [CLINICAL GUIDELINES FOR DIAGNOSIS, TREATMENT AND MONITORING OF PATIENTS WITH INVASIVE BREAST CANCER--CROATIAN ONCOLOGY SOCIETY]. AB - Breast cancer is the most common cancer in women. It can be diagnosed in early stage through screening, early detection and educational programs, and when diagnosed early it can be efficiently treated. Treatment modalities include surgery, chemotherapy, radiotherapy, hormonal therapy and targeted biologic therapy, according to the stage of the disease and patient condition. Treatment decisions should be made after multidisciplinary team discussion. Due to the significance of this disease it is important to define and implement standardized approach for diagnostic, treatment and monitoring algorithm as well. The following text presents the clinical guidelines in order to standardize the procedures and criteria for diagnosis, management, treatment and monitoring of patients with breast cancer in the Republic of Croatia. PMID- 26380472 TI - [DIFFERENCE IN THE PREVALENCE OF BURNOUT SYNDROME IN PRECLINICAL AND CLINICAL TEACHING DOCTORS OF MOSTAR SCHOOL OF MEDICINE]. AB - AIM: The aim of this study was to determine the difference in the prevalence of burnout syndrome in preclinical and clinical teaching doctors of Mostar School of Medicine in the academic year 2011/2012. Special attention was also focused on finding out the possible difference between the syndrome incidence that was correlated to gender and years of service. The main hypothesis was that the probability of burnout syndrome incidence was higher in the group of female clinical teaching doctors having more years of service. SUBJECTS AND METHODS: The study involved 62 people with high academic education employed at Mostar School of Medicine who were surveyed during a randomly selected consecutive 3-month period (February to May) of the academic year 2011/2012. The data were prospectively collected through a standardized questionnaire survey. The studied parameters were gender, years of work experience and the engagement in preclinical or clinical departments of the Medical School. RESULTS: The survey showed that 43 out of 62 (69.4%) respondents did not suffer the burnout syndrome, while moderate syndrome was recodred in 19 (30.6%) of them. No person had serious symptoms of the syndrome. The difference between the respondents who suffered the syndrome and those who did not was not statistically significant (P=0.002). Considering the gender of respondents, statistically significant differences were not confirmed (P=0.444). Considering the years of service, the highest incidence of the syndrome was found in people with more work experience (in the group of 21 25 years), but the difference between the groups was not statistically significant (P=0.271). Observing the work in preclinical and clinical departments, because of the limited number of patients we could not confirm the hypothesis. The syndrome had affected 13 (21%) clinical teaching doctors and 6 (9,7%) preclinical doctors, while the differenece between them was not statistically significant (P=0.054). CONCLUSION: Considering the results of this research, it has not been proven that the burnout syndrome occurred more frequently in doctors who were involved in clinical teaching than in doctors who tought in preclinical departments. Also, there was no difference in the appearance of the syndrome that was related to gender and years of service. PMID- 26380473 TI - [PREDICTORS OF POOR BOWEL PREPARATION FOR COLONOSCOPY: A SINGLE-CENTRE PROSPECTIVE STUDY]. AB - Adequate bowel preparation is the key of a successful colonoscopy. The aim of the study was to analyze sociodemographic and clinical characteristics in our population of patients referred for colonoscopy. Bowel cleanness was evaluated using the Boston Bowel Preparation Scale (BBPS) where values 7 were considered a criterion of successful bowel preparation. The study involved 286 subjects (61.5% male, median 61 years, interquartile range 50-71). BBPS score 7 was found in 145 subjects (50.7%). Multivariate analysis indicated that subjects with severe comorbidity (ASA status 3, OR = 0,29; 95% CI: 0.12-0.72; p = 0,008) represented a risk factor for poor bowel preparation. Regimens with polyethyleneglycol (PEG) were superior compared with other protocols (OR = 2.54; 95% CI: 1.27-5.10; p = 0.008). Timing of the colonoscopy also contributed to better bowel preparation (OR = 5.50; 95% CI: 2.07-14.67; p = 0.001). This study confirms that presence of comorbidity and non-use of PEG regimens are predictors of poor bowel preparation in our population of patients referred for colonoscopy. PMID- 26380474 TI - [CLAVICLE FRACTURES IN CHILDREN--CIRCUMSTANCES AND CAUSES OF INJURY]. AB - Clavicle fractures in children occur twice as often as in adults. During a child's growth period they account for 10-15% of all fractures sustained. The questions which should be asked are how these fractures are sustained and under which circumstances are the children injured. In the study 256 children with clavicle fractures treated during the period 2008-2013 were analyzed. The underlying cause and place of injuries were classified using the ICD-10 classification system, using environmental causes of injury. The circumstances were in each case accidental injury. Environmental causes were traffic accidents (V01-V99) or mishaps/accidents (W00-X59). Fracture injuries were caused in traffic accidents in 24 (9.4%), and in mishaps/accidents in 232 (90.6%) children. Of the injuries caused by mishaps/accidents, in 204 children these were caused by falls (W00-W19). In 123 of them the injuries were caused by falls from a ground level, and in 81 were from a greater height. Direct blow injuries, caused by another person or a blunt instrument, weere the causes of fractures seen in 28 children. Place of fracture sustainment was dominantly at home. This was followed by injuries sustained outside in recreational areas, while least were suffered at school or kindergarden facilities. Bicycle riding was the cause of clavicle fractures in 48 children, which was 18.7% of all fractures seen. Sports related injuries and fractures were seen in 47 (18.4%) out of 256 children: 30 in football, 10 in defensive sports (wrestling, judo, karate), three in hockey, while basketball and gymnastics accounted for two each. Preschool children were injured more often while in the care of their parents while school aged children were adaquately protected, but in after-school activities they were often injured. The most common injuries after school were those suffered in traffic accidents and recreational sports activities. In the adolescent period, the most common injuries seen were again those in traffic accidents, bicycle riding, recreational sports activities and injuries sustained at home. PMID- 26380475 TI - [COLONIC MUCO-SUBMUCOSAL ELONGATED POLYP: A CASE REPORT AND LITERATURE REVIEW]. AB - Recently a new entity has been described--a colonic muco-submucosal elongated polyp (CMSEP)--that did not fall into traditional classification of colorectal polyps. The CMSEP is endoscopically characterised by elongated, worm-like appearance with a normal overlying mucosa. Histologic characteristics of the CMSEP comprise mucosa and expanded submucosa with dilated vasculature and lymphatics. Herein, we report a case of CMSEP, that to the best of our knowledge, has not been previously described in our literature. With regard to the on-going National colorectal cancer screening programme, our intention is to draw attention of gastrointestinal pathologists and endoscopists to this distinctive and very rare phenomenon. PMID- 26380477 TI - [VATS THYMECTOMY IN MYASTHENIA GRAVIS TREATMENT--A CASE REPORT]. AB - Myasthenia gravis (MG) is a chronic autoimmune disease characterized by weakness of skeletal muscles, specifically ocular. Relationship between the thymus gland and MG is not fully understood yet. Thymectomy is recommended for individuals with thymoma, but should be considered in all patients under 60 years of age with generalized MG in cases with no thymomatous tissue. We report a 27-year-old female patient with ocular type myasthenia gravis and radiological findings of anterior mediastinal mass, treated by VATS thymectomy. The intervention was carried out by 3-portal right-sided thoracoscopic approach. Single-lung ventilation and carbon-dioxide insufflation provided working space, and harmonic scalpel was used for the dissection and ligation. The patient's postoperative course was uncomplicated and the patient was discharged on the third postoperative day. The aim of our case report is to stress the importance of VATS technique in faster recovery and better cosmetic effect than in sternotomy procedures. PMID- 26380476 TI - [GOODPASTURE'S SYNDROME--CASE REPORTS]. AB - Goodpasture's syndrome is a rare clinical entity characterized by rapidly progressive glomerulonephritis, diffuse pulmonary hemorrhage and the presence of circulating autoantibodies to the glomerular basement membrane (GBM). Autoantibodies bind to reactive epitopes of noncollagenous domain of the collagen type IV alpha-3 chain in glomerular and alveolar basement membranes. Autoantibodies activate the complement cascade resulting in tissue injury by the type II hypersensitivity reaction according to the Coombs and Gell classification of antigen-antibody reactions. Prognostic factors include the renal excretory function and the degree of renal and lung damage at the time of presentation. Prompt diagnosis and early and adequate medical treatment is vital for patients. Clinical treatment must be aggressive in order of achieving better outcome. This article describes three patients who clinically presented with renopulmonary syndrome, renal failure, hematuria, proteinuria and hemoptysis. Kidney biopsy diagnosis was crescentic glomerulonephritis due to antibodies against GBM. In all three patients we started therapy with glucocorticoids and cyclophosphamide combined with plasma exchange therapy. In two patients who initially had severe impairment of renal function and high percentage of crescents in the renal biopsy, kidney function recovery was not achieved. In one patient, who at the time of clinical presentation showed milder renal failure and lower percentage of crescents in renal biopsy, the full recovery of renal function was obtained. PMID- 26380478 TI - [AMIODARONE AND THE THYROID FUNCTION]. AB - Amiodarone is a benzofuran derivative that contains up to 40% of iodine. Amiodarone is used for treatment and prevention of life threatening supraventricular and ventricular tachyarrhythmias. The effects on thyroid gland vary from abnormalities in thyroid function tests to overt amiodarone induced hypothyroidism (AIH) and thyrotoxicosis (AIT). Patients with AIH are treated with L-thyroxine and may continue treatment with amiodarone. Two different forms of AIT have to be distinguished: amiodarone induced hyperthyroidism (AIT I) and thyroiditis (AIT II). AIT I is treated with antithyroid drugs, while total thyroidectomy and iodine-131 are used for definitive treatment. AIT II is treated with glucocorticoids. Patients with AIT have to stop treatment with amiodarone. Dronedarone is a less potent antiarrhythmic agent with structural and pharmacological properties similar to amiodarone. Dronedarone is devoid of iodine with fewer adverse effects and therefore it may be used in high risk patients for development of AIT or AIH. PMID- 26380479 TI - [MICROARRAY AND GENE EXPRESSION ANALYSIS]. AB - Microarray gene expression analysis is high-throughput method in which many different sized DNA molecules are attached to solid surface in designated spots. These molecules are used for the discovery of specific RNA molecules isolated from various biological samples of interest. Core principle of this method is hybridization of complementary nucleotides (A-T and G-C), which leads to creation of double stranded nucleic acids. Gene expression differences in two groups of samples are discovered and quantificated by comparison of signal intensity values in microarray spots. Systemic analysis of data gathered in microarray gene expression measurement is performed by various bioinformatic methods such as group analysis, annotation analysis as well as network and pathway analysis. Expression comparison of all genes in different cells of the same individual or same cells of different individuals provides an insight into the mechanism responsible for development of a certain condition or disease. PMID- 26380480 TI - [STRATEGY OF USE AND MAINTENANCE OF CLINICAL HOSPITAL CENTER RIJEKA IN ACCORDANCE WITH KEY PERFORMANCE INDICATORS FOR STRATEGIC HEALTHCARE FACILITIES MAINTENANCE]. AB - Building usage is the phase in the building life cycle that is most time consuming, most functional, most significant due to building purpose and often systematically ignored. Maintenance is the set of activities that ensure the planned duration of facility exploitation phase in accordance with the requirements for quality maintenance of a large number of important building features as well as other elements immanent to the nature of facilities' life. The aim of the study is to show the analysis of the current state of organized, planned and comprehensive managerial approach in hospital utilization and maintenance in the Republic of Croatia, given on the case study of Clinical hospital center in Rijeka. The methodology used consists of relevant literature section of theory of facility utilization, maintenance and management in general, hospital buildings especially, display of practice on case study, and comparison of key performance indicators values obtained through interview with those that author Igal M. Shohet defined in his study by field surveys and statistical analyses. Despite many positive indicators of Clinical hospital center Rijeka maintenance, an additional research is needed in order to define a more complete national hospital maintenance strategy. PMID- 26380481 TI - [Some more on Croatian medical nomenclature, language editor's comments]. PMID- 26380483 TI - [Not Available]. PMID- 26380482 TI - [Not Available]. PMID- 26380485 TI - Number of Intermediate Follicles. An Independent Risk Factor of Multiple Pregnancies in Intrauterine Insemination Cycles with Recombinant Follicle Stimulating Hormone. AB - OBJECTIVE: To identify risk factors for multiple pregnancies in intrauterine insemination (IUI) cycles with recombinant follicle-stimulating hormone (r-FSH). STUDY DESIGN: A retrospective study including 205 IUI cycles with r-FSH which led to clinical pregnancies was conducted. A total of 145, singleton pregnancies and 60 multiple pregnancies were compared according to clinical characteristics and parameters of ovarian stimulation and IUI procedure. The relationships between size and number of follicles and serum estradiol (E2) levels and the risk of multiple pregnancies were investigated using multiple logistic regression analyses. RESULTS: The means of infertility length, serum E2 levels, the number of follicles 10 mm, 12 mm, and >= 16 mm, and the number of intermediate follicles (from 12 to <= 15 mm) at the day of ovulation triggering were significantly higher in the multiple pregnancy group as compared to in the singleton pregnancy group (p < 0.05). We first demonstrated that high E2 levels (>= 1,000 pg/nL) and the number of intermediate follicles represent 2 independent and significant risk factors for multiple gestation in IUI cycles that used ovarian stimulation by r FSH (p = 0.002 and p = 0.007, respectively). CONCLUSION: This study shows that high E2 levels and the number of intermediate follicles, independently of large follicles, can predict an increased risk of multiple pregnancy in r-FSH IUI cycles. PMID- 26380486 TI - Vaginal Swab Levels of CA125 Are Related to Time of Cycle in Ovulatory Women. A Pilot Study. AB - OBJECTIVE: To develop an assay for vaginal CA125 and determine if vaginal levels correlate with the phase of the menstrual cycle. STUDY DESIGN: Fifteen women through a total of 20 ovulatory cycles obtained daily vaginal swabs for assay. Sampling began within the first 3 days after menses in and continued into the luteal phase. The subjects eluted the cotton swab tips in vials containing a standard volume of water. At the completion of each cycle the vial concentrations of CA125 were measured with the Siemens IMMULITE 2000. These "Qvaginal" levels of CA125 were indexed to the first day of positive urine luteinizing hormone signal, day 0. RESULTS: Qvaginal CA125 levels ranged from background (< 1 U/mL) to 5,740 U/mL and followed a periodic pattern: low during the early preovulatory phase, a maximum generally during day -4 to day +1, and low during the luteal phase. Qvaginal CA125 levels during the interval of presumptive fertility, day -4 to day +1, were statistically higher than levels during the preovulatory interval ending at day -5 and the postovulatory interval starting at day +2 (p value < 0.02). CONCLUSIONS: The vaginal swab assay for CA125 can potentially track the phase of the ovulatory cycle and therefore may have applications for fertility awareness and diagnosis of reproductive disorders. PMID- 26380487 TI - Use of Gammaglobulin to Lower Elevated Natural Killer Cells in Patients with Recurrent Miscarriage. AB - OBJECTIVE: To evaluate the effectiveness of intravenous immunoglobulin (IVIG) in patients presenting with recurrent miscarriage and abnormally elevated natural killer (NK) cells. STUDY DESIGN: This retrospective patient controlled evidence level II-2 pilot study was conducted at Cohen Center, P.A., Medical City Dallas Hospital. Ninety women with a history of recurrent miscarriage (average, 5) and elevated NK cells were retrospectively evaluated to document the outcome of their treatment with IVIG. RESULTS: Of 90 women with elevated NK cells who received IVIG treatment, 78 (86.7%) became pregnant. Sixty-four (82.0%) of those pregnancies had a successful viable outcome. Fourteen (18.0%) gestations ended as first trimester miscarriages. CONCLUSION: We conclude at evidence level II-2 that, with adequate precautions, low-dose IVIG therapy is safe and effective for women with immunologic abortion and documented abnormally elevated NK cells. PMID- 26380488 TI - Screening for Chlamydia and Gonorrhea Cervicitis and Implications for Pregnancy Outcome. Are We Testing and Treating at the Right Time? AB - OBJECTIVE: To evaluate the effect of gonorrheal and chlamydial cervicitis (GCC) on the risk of preterm labor (PTL) and preterm premature rupture of membranes (PPROM). STUDY DESIGN: A large cross-sectional sample of patients (N = 1,120) was studied. Data on samples for GCC and pregnancy outcome were entered into a database from a retrospective chart review. RESULTS: There were 1,120 pregnancies with adequate data for analysis. Of those pregnancies 933 were unaffected by GCC, and 187 were affected. The rates of preterm delivery were 17.79% and 16.58% for GCC-negative and GCC-positive pregnancies, respectively. PPROM occurred in 3.97% and 2.67% of GCC-negative and GCC-positive pregnancies, respectively. PTL occurred in 8.25% and 8.02% of GCC-negative and GCC-positive pregnancies, respectively. No outcomes met statistical significance. When pregnancy outcomes were analyzed by trimester of infection, there was a higher risk of preterm delivery but not preterm labor with earlier infection. This did meet statistical significance. There was a trend towards lower rate of cesarean section in the infected group of patients, which did not meet statistical significance. CONCLUSION: Maternal infection with gonorrhea and/or chlamydia is not associated with PPROM or PTL. PMID- 26380489 TI - Is Intracytoplasmic Sperm Injection Success Affected by the Testicular Histopathology in Nonobstructive Azoospermic Patients? AB - OBJECTIVE: To investigate whether the histological changes observed in testicular tissue might be correlated with pregnancy outcome in intracytoplasmic sperm injection-testicular sperm extraction (TESE) cycles in nonobstructive azoospermic patients. Embryo quality was also tested in various types of histology. STUDY DESIGN: We retrospectively analyzed the pathology results of 209 testicular biopsies from nonobstructive azoospermic patients in our assisted reproductive technologies clinic. According to the final pathology reports, the study group was divided into the following categories: Group A (Sertoli-cell-only), Group B (maturation arrest), Group C (hypospermatogenesis), Group D (normal spermatogenesis), and Group E (mixed pattern). RESULTS: Spermatozoa were identified in 114 of 209 cases (54.5%). Sperm retrieval and presence of motile spermatozoa after TESE was highest in normal spermatogenesis and lowest in Sertoli-cell-only groups. Fertilization rate was highest in the normal spermatogenesis and hypospermatogenesis groups. Embryo grades on day 3 were comparable between groups. Clinical pregnancy per embryo transfer was also similar. Both fertilization and clinical pregnancy rates were statistically higher in favor of motile spermatozoa group. CONCLUSION: Testicular histopathology not only gives information regarding the probability of retrieving sperm at TESE, but also is a good predictor of fertilization. Once a motile spermatozoon is identified, the chance of clinical pregnancy might improve probably due to relatively good optimal microenvironment within the testis. PMID- 26380490 TI - Development of an Endometrial Ablation Model in New Zealand White Rabbits. AB - OBJECTIVE: To develop an animal model for radiofrequency endometrial ablation (EA) and evaluate histopathologic outcomes of EA in New Zealand White (NZW) rabbits. STUDY DESIGN: A pilot study was conducted. A radiofrequency EA device was developed and a variety of EA settings were tested on euthanized NZW rabbits. An algorithm was developed to determine target EA parameters. Bilateral radiofrequency EA was performed via laparotomy using 5.2 mm, 6.1 mm, or 7.1 mm diameter x 100 mm bipolar probes on 10 live NZW rabbits. All rabbits were screened for endometrial cancer (EC). Rabbits were euthanized 3 weeks following EA, and histopathologic analysis of postablation hysterectomy specimens was performed. RESULTS: Bilateral radiofrequency EA was successful in rabbits that were candidates for the procedure, and uterine assessment was feasible in all rabbits. One case of EC was detected. Uterine anatomy was variable among rabbits. The optimal EA setting was 4.5 W/cm2 x 20 seconds, which provided consistent thermal destruction to the endometrium and inner myometrium as verified by histology. CONCLUSION: Use of a radiofrequency EA algorithm tailored to individual NZW rabbits produces consistent thermal destruction of the endometrium and inner myometrium. This animal model can be used to study the long-term consequences of EA and the association with EC. PMID- 26380491 TI - Institute of Medicine Guidelines for Appropiate Pregnancy Weight Gain for Obese Women May Be Too High. AB - OBJECTIVE: To investigate how the 2009 Institute of Medicine (IOM) guidelines for pregnancy weight gain for obese women relate to the longer-term outcome of childhood obesity. STUDY DESIGN: Maternal, neonatal, soioeconomic, and nutritional histories were collected for mothers with children age 2-5 years old. Women in each body mass index (BMI) category were categorized based on under, appropriate (AG), and over weight gain per IOM guidelines and compared with rates of childhood obesity in each category. RESULTS: A total of 502 mother-child pairs were enrolled; 36.4% of women were obese at the start of pregnancy. Obese women who were AG by IOM guidelines were more likely than underweight, normal weight, and overweight women to have obese offspring (29.5% vs. 14.2%, p = 0.04). The BMI percentiles of the offspring of obese AG women were 10 percentile points higher than the 55th percentile of the other groups. CONCLUSION: The 2009 IOM pregnancy weight gain guidelines for obese women may still be too high when considering longer-term outcomes such as childhood obesity. Further studies are needed. PMID- 26380492 TI - Clinical Significance of Pyometra. AB - OBJECTIVE: To review the clinical profiles and management outcomes of patients with pyometra. STUDY DESIGN: A retrospective review of all women admitted with a confirmed diagnosis of pyometra over an 8-year period (January 2003 to December 2010). The medical records, including operation notes, histological and microbiological results, were reviewed. RESULTS: A total of 57 patients accounting for 76 admissions were identified. The mean patient age was 82.0 +/- 11.3 years. The most common presenting symptom was postmenopausal bleeding (59.2%), followed by vaginal discharge (40.8%), fever (6.6%), and abdominal pain (5.3%). Drainage of pyometra was either by uterine Foley catheter insertion (48 patients [84.2%]) or repeated endometrial aspiration (2 patients [3.5%]). Antibiotics were prescribed to 49 patients (86.0%). Diagnostic hysteroscopy with mechanical cervical dilation was performed in 6 patients (10.5%). Gynecological malignancy was identified in only 1 patient, while colorectal cancer was identified in 2 patients. No patient had spontaneous uterine perforation or sepsis. Sixteen patients had recurrent pyometra within a mean follow-up period of 5.1 +/- 5.8 months (range, 0.5-23 months). CONCLUSION: Pyometra usually presents with postmenopausal bleeding and can be treated with drainage and antibiotics treatment. In contrast to previous reports, our study indicates that spontaneous uterine perforation and gynecological malignancies are not commonly associated with pyometra. PMID- 26380493 TI - Is Laparoscopic Incidental Appendectomy in Gynecological Diseases Related to Postoperative Intraabdominal Infection and Complications? AB - OBJECTIVE: To establish whether laparoscopic incidental appendectomy in gynecological diseases is related to postoperative intraabdominal infection and complications. STUDY DESIGN: This study was performed prospectively in 443 patients who underwent laparoscopic surgery without appendectomy (n = 222) or with appendectomy (n = 221). On postoperative day 1, drain fluid was cultured in all patients. All data were compared using Student's t test and chi2 test. RESULTS: Bacteria grew in cultures of 93 patients (21.0%): 38 (17.1%) in the nonappendectomy group and 55 (24.9%) in the appendectomy group (p < 0.01). There were statistical differences in the incidence of bacterial growth, postoperative complications, and post-operative laboratory changes for percentage of neutrophils (p < 0.01) and C-reactive protein (p < 0.01). Thirteen genera of bacteria grew in the drain culture. The 9 commensal organisms of the human intestine were identified in all patients, each 8 genera of bacteria in both groups. The surgical type did not affect the postoperative drain culture results. CONCLUSION: Postoperative bacterial growth and complications were increased in the laparoscopic incidental appendectomy group. Infections with bacteria from the intestine in both groups were also related to contamination during surgery and postoperative care. PMID- 26380494 TI - Coping with the Stress of Infertility. Males Versus Females. AB - OBJECTIVE: To investigate ways of coping with stress in infertile men and women. STUDY DESIGN: The study population was composed of 255 women and 238 men (total, 493) admitted to an infertility clinic between May 2012 and December 2012. A questionnaire was used to gather information and the Ways of Coping inventory was used for the evaluation of patients. RESULTS: The mean age of the study population was 28.33 +/- 5.59 (mean +/- SD) for females and 31.60 +/- 5.64 for males. We found similar coping scores for men and women in all subscales (Self confident, Desperate, Obedient, Optimistic, Social Support Seeking) (p > 0.05). The variables affected Coping with Stress Scores in a similar way for both women and men except for "age" and "the desire for psychological support." The Optimistic approach score was worse in men over age 35 and better in those desiring psychological support in both sexes (p < 0.05). CONCLUSION: Infertile men and women use similar coping strategies and have similar coping scores. They mainly use active strategies at a moderate level. Increasing age in the male group, and lack of desire for psychological support in both sexes, are the factors negatively affecting the Optimistic approach scores. PMID- 26380496 TI - Emergent Oocyte Cryopreservation with a Novel Ovarian Transposition Technique in a Colorectal Cancer Patient: A Combined Approach for Fertility Preservation. A Case Report. AB - BACKGROUND: Fertility preservation has become a standard of care in reproductive age oncology patients. However, research has demonstrated that the knowledge of the provider and referral practice patterns remain suboptimal. Fertility preservation should be discussed with oncology patients of reproductive age, with the full knowledge of the individual. A combined medical and surgical approach may further ensure their reproductive successes in the future. CASE: A 38-year old, nulliparous woman with colorectal cancer desired fertility preservation prior to cancer therapy. She underwent a laparoscopic ovarian transposition using a novel percutaneous suturing technique after emergent ovarian stimulation, followed by oocyte retrieval and cryopreservation. One year after chemotherapy and pelvic radiation the patient resumed regular menstrual cycles. CONCLUSION: A combined approach using emergent oocyte cryopreservation and a novel laparoscopic ovarian transposition is an optimal fertility preservation strategy in women with colorectal cancer. Fertility preservation success is dependent upon a multidisciplinary approach of well-informed medical teams consisting of an oncologist, a surgeon, a radiation oncologist, and a reproductive specialist. PMID- 26380495 TI - Diminished Utilization of in Vitro Fertilization Following Ovarian Transposition in Cervical Cancer Patients. AB - OBJECTIVE: To assess subsequent utilization of fertility treatment in reproductive-age women with cervical cancer (CC) who underwent ovarian transposition (OT) to preserve fertility prior to pelvic radiation. STUDY DESIGN: This is a case series of 216 CC patients seen in a comprehensive cancer center. Sixteen patients underwent OT for fertility preservation prior to pelvic radiation. Patients were assessed for utilization of fertility treatment, follicle-stimulating hormone (FSH) levels as a measure of ovarian reserve, and functional assessment of chronic illness therapy-cervix cancer (FACT-CX) to assess quality of life after OT. RESULTS: Of the patients, 94% of patients [corrected] maintained regular menstrual cycles 3 years after ovarian transposition (OT) [corrected] surgery (15/16). When measured (n = 5), serum FSH was normal at baseline and showed a transient elevation at 3 months following chemoradiation, with a return to normal levels at 6 months (means, 6.33 +/- 2.94, 48.44 +/- 18.63, and 12.52 +/- 8.25 mIU/mL, respectively). Only 1 patient in this series attempted fertility treatment (in vitro fertilization) following OT, and she did not become pregnant. FACT-CX indicated that quality of life did not change significantly over the 6 months' duration following OT and chemoradiation therapy. CONCLUSION: OT preserves menstrual cycle regularity without negatively impacting patients' quality of life. The utility of OT as an effective fertility preservation option is hampered by the low utilization rate of in vitro fertilization and lack of ovarian reserve assessment following OT. PMID- 26380497 TI - Wandering Spleen. A Case of Spontaneous Hemoperitoneum in an HIV-positive Patient with Recurrent Tuboovarian Abscess. AB - BACKGROUND: Wandering spleen is a rare and potentially devastating condition that can present in a variety of ways. Here we present a case that led to acute abdomen and hemoperitoneum in a young woman. CASE: A 27-year-old woman with a history of human immunodeficiency virus (HIV), pelvic inflammatory disease, and tuboovarian abscess was readmitted to the hospital for intravenous antibiotic treatment. When her clinical picture did not improve, she underwent placement of a pelvic drain for abscess drainage. Overnight she developed an acute abdomen and hemorrhagic shock. She was taken to the operating room for an exploratory laparotomy, which revealed a ruptured spleen with a single, elongated vascular pedicle. CONCLUSION: Wandering spleen is a rare diagnosis, more common in reproductive-aged women, with potentially fatal complications. It is a necessary component of a differential diagnosis for acute abdomen in reproductive-aged women. PMID- 26380498 TI - Vertebral Osteomyelitis in Pregnancy from a Methicillin-resistant Staphylococcus Aureus Vulvar Abscess. A Case Report. AB - BACKGROUND: Osteomyelitis is a rare problem in pregnancy but can present challenges for diagnosis and treatment. This case report describes a patient with a history of vulvar abscess who developed methicillin-resistant Staphylococcus aureus (MRSA) bacteremia and osteomyelitis during pregnancy. CASE: A 20-year-old woman, gravida 1, at 33 weeks' gestation, developed sepsis from MRSA bacteremia after a vulvar abscess drainage. She developed acute respiratory distress syndrome (ARDS) and was found to have osteomyelitis on her thoracic spine level 7. The diagnosis of osteomyelitis was based on clinical findings and magnetic resonance imaging. An emergent cesarean section was undertaken due to worsening ARDS. The osteomyelitis was treated with intravenous daptomycin with symptomatic improvement. However, back pain returned and the patient was readmitted and required a spinal brace and 6 weeks of intravenous vancomycin. CONCLUSION: Osteomyelitis in pregnancy is a rare complication and a challenging diagnosis that requires a high index of suspicion. The treatment of osteomyelitis in pregnancy versus nonpregnancy is the same. This case is unique because this pregnant patient developed osteomyelitis secondary to a vulvar abscess. PMID- 26380499 TI - Furcate Umbilical Cord Insertion: Disparate Outcomes of a Rare Obstetrical Finding. A Case Report. AB - BACKGROUND: Furcate umbilical cord insertions are rare obstetrical findings. This variant is defined by an umbilical cord which branches prior to contacting the placental surface. The vessels are left vulnerable to injury as they often separate from the cord substance. CASES: In case 1, a duplex placenta and bifurcate umbilical cord were diagnosed at routine anatomy ultrasound, and no significant fetal anomalies were associated with these findings. There was difficulty with placental extraction, leading to postpartum dilation and curettage. In case 2, the furcate umbilical cord was diagnosed on postpartum evaluation after emergent delivery. It was found in conjunction with VACTERL association of the fetus. CONCLUSION: Abnormal placentation and umbilical cord insertion can be diagnosed prenatally. Earlier recognition will allow for earlier identification of possible associated fetal anomalies, delivery planning, and close observation for maternal and fetal complications. PMID- 26380501 TI - Patch: A Skin Lesion in Need of Definition. PMID- 26380500 TI - Cutaneous Adaptations and Subcutaneous Soft Tissue Alterations Following Mechanical Stress: The Coxsackie A6 Virus May Offer a Solution. PMID- 26380502 TI - Topical Nitroglycerine in Perniosis/Chilblains. AB - The treatment of perniosis is largely inadequate. The success rate of 0.2% nitroglycerine ointment is demonstrated in the present series. Twenty-two patients clinically diagnosed with severe perniosis were prescribed the topical vasodilator nitroglycerine. Digital photography and patient self-report of the clinical appearance, degree of irritation, and pain and soreness of the lesions were assessed on a 3-point scale to assess therapeutic response. A total of 18 of the 22 patients had regression of the lesions within the first week of treatment and complete regression in 2 weeks. Of these patients, 2 who experienced a relapse were successfully treated with another course of topical nitroglycerine. Two of 22 patients had regression of the lesions during the second week and complete regression in another week. Response was delayed in patients with a longer duration of disease. Topical 0.2% nitroglycerine ointment may be a promising alternative treatment option in perniosis. PMID- 26380503 TI - Oral Finasteride Presents With Sexual-Unrelated Withdrawal in Long-Term Treated Androgenic Alopecia in Men. AB - Side effects associated with oral finasteride (FT) (1 mg/d) and topical 5% minoxidil (M5) have been previously described. The authors have evaluated long term adverse effects and causes of long-term therapy withdrawal in patients with androgenic alopecia (AGA) treated with M5+FT vs M5 without FT. A total of 130 AGA patients with a minimum 2-year follow-up volunteered to complete a questionnaire on side effects. Patients' responses were classified as "never," "rarely," "sometimes," "often," and "all the time." An adverse effect was considered in the presence of an "often" or "all the time" response. A total of 100 patients received combined M5+FT and were compared with 30 patients receiving single therapy M5 according to the physician's clinical criteria. Erectile dysfunction (3%), diminished libido (4%), and reduced ejaculation (7%) were present in patients taking M5+FT but were absent in patients taking M5. Only 1 of 100 patients taking M5+FT quit long-term therapy due to sexual adverse effects (diminished libido). The main causes for therapy withdrawal in the FT group were lack of positive results in 11% and in the M5 group side effects in 4% (P < .02). Increased body hair was different between groups: with 6.6% in the M5 group and 4% in the M5+FT group (P < .03). FT demonstrates sexual-unrelated reasons as the main cause of therapy withdrawal in long-term treated AGA patients. PMID- 26380504 TI - Topical Minoxidil: Systematic Review and Meta-Analysis of Its Efficacy in Androgenetic Alopecia. AB - Topical minoxidil has become a mainstay in the treatment of androgenetic alopecia (AGA). Despite being a longstanding treatment for AGA, relatively few reviews of its efficacy have been published. The current study sought to synthesize the available efficacy data by performing a systematic review of the literature and conducting random-effects pairwise meta-analyses for the outcomes percent increase in hair count from baseline, investigator assessment, and patient self assessment. Results showed that minoxidil is more effective than placebo in promoting total and nonvellus hair growth (mean difference [MD], 16.68; 95% confidence interval [CI], 9.34-24.03 and MD, 20.90; 95% CI, 9.07-32.74). A significantly higher proportion of participants in the minoxidil group had greater hair growth than participants in the placebo group as judged by both investigators and self-reports (relative risk [RR], 2.28; 95% CI, 1.58-3.31 and RR, 1.56; 95% CI, 1.34-1.80). Despite significant clinical efficacy, cosmetically acceptable results are present in only a subset of patients. Compliance is thought to be a major limiting factor and is being addressed by novel formulations and combinations. PMID- 26380505 TI - Cosmetic Regulations: A Comparative Study. AB - The regulatory framework, compliance requirement, efficacy, safety, and marketing of cosmetic products are considered the most important factors for growth of the cosmetic industry. There are different regulatory bodies across the globe that have their own insights for regulation; moreover, governments such as the United States, European Union, and Japan follow a stringent regulatory framework, whereas cosmetics are not so much strictly regulated in countries such as India, Brazil, and China. The alignment of a regulatory framework will play a significant role in the removal of barriers to trade, growth of market at an international level, innovation in the development and presentation of new products, and most importantly safety and efficacy of the marketed products. The present contribution gives insight into the important cosmetic regulations in areas of premarket approval, ingredient control, and labeling and warnings, with a special focus on the cosmetic regulatory environments in the United States, European Union, Japan, and India. Most importantly, the authors highlight the dark side of cosmetics associated with allergic reactions and even skin cancer. The importance of cosmetic regulations has been highlighted by dint of which the society can be healthier, accomplished by more stringent and harmonized regulations. PMID- 26380506 TI - The Use of Traditional Chinese Medicine in Some Dermatologic Diseases: Part II- Autoimmune Bullous Disorders and Lichen Planus. AB - Over the centuries, traditional Chinese medicine (TCM) and Western medicine have traveled along parallel lines with no opportunity for collaboration. In recent decades, while an interest in TCM has been growing among Western clinicians, progress has been made in the comprehension of pathogenic mechanisms of skin disorders, and the communication between Western and Eastern medicines has become more and more intensive. In this paper, the authors discuss TCM remedies used in the treatment of autoimmune bullous disorders (pemphigus and bullous pemphigoid) and lichen planus. Future studies on the active components of the TCM will certainly shed new light on the still obscure aspects of some dermatologic diseases. PMID- 26380507 TI - Basal Cell Carcinoma. Part 1: Basal Cell Carcinoma Has Come of Age. AB - Almost 2 centuries after its recognition, basal cell carcinoma (BCC) remains the most common cancer worldwide, with a 30% overall lifetime risk in the United States and an incidence that continues to increase annually. The increasing incidence of BCC is multifactorial and likely correlates to multiple risk factors, including exposure to both ionizing and UV radiation. Despite its relatively indolent growth, what was once referred to as a rodent ulcer or basal cell epithelioma is now identified as a full-fledged malignancy. The authors describe the societal burden of this disease and characterize its malignant potential, emphasizing associated clinical and histopathologic prognostic features. PMID- 26380508 TI - Attack of the Living Dead: Why You Need a GMS Stain With a PAS Stain to Detect Fungi in Dermatopathology Specimens. PMID- 26380509 TI - 1% Ivermectin Cream (Soolantra) for the Treatment of Rosacea. PMID- 26380511 TI - Necrotic Carpal Tunnel Syndrome: A Standard Deviation From the Median Nerve. PMID- 26380510 TI - XELJANZ (Tofacitinib) for Chronic Plaque Psoriasis. PMID- 26380512 TI - Patch Testing Pearls: Solutions to Common Clinical Dilemmas. PMID- 26380513 TI - Dissecting Cellulitis. PMID- 26380514 TI - Onychomycosis. PMID- 26380515 TI - Weightlifter's Nodule: A New Variant of Athlete's Nodule. AB - A 17-year-old high school football player presented to our dermatology clinic complaining of two asymptomatic lumps on the upper part of his back. The first lump was noticed on the right side of the upper aspect of his back following a weightlifting session. The second lump appeared on the left side of the upper part of his back several weeks later. The patient's personal and family medical history was unremarkable. Physical examination revealed an ill-defined, firm, mobile subcutaneous nodule measuring approximately 3 cm on the right upper part of the back and a similar but smaller nodule on the left upper portion of the back (Figure 1). The location of the lesions corresponded to the areas of maximal pressure produced by a squat bar that he uses frequently during weightlifting (Figure 2). Histologic analysis of the right lesion revealed a markedly expanded dermis caused by a striking increase in the number of collagen bundles that were relatively normal in thickness, accompanied by a subtle increase in the number of fibroblasts (Figure 3). In some foci, fibroplasia along with increased deposition of mucin further contributed to the expansion of the dermis (Figure 3). Although the process spanned the entire dermis, it was more pronounced in the deep reticular dermis, particularly near the subcutis as collagen bundles were arranged in a more haphazard array in this region. Verhoeff-Van Gieson stain revealed diminished and fragmented elastic fibers within some of the involved areas. This reactive fibrosis can be seen in athlete's nodules as a result of repetitive blunt pressure. We proposed a diagnosis of weightlifter's nodule to further classify these lesions and the patient was instructed to discontinue associated weightlifting activities. PMID- 26380516 TI - Chromoblastomycosis Caused by Cladophialophora bantiana in a Renal Transplant Recipient From Delhi, India. AB - A 45-year-old accountant residing in Delhi, India, presented to our dermatology clinic with a small asymptomatic plaque on the little finger of his left hand of 3 months' duration. The onset of the lesion was insidious and gradually progressed to 4 cm across at the time of his first visit. The patient had undergone renal transplantation twice (the first procedure 3 months prior and the second 18 months prior). Since then, he had been receiving cyclosporine A (400 mg daily) and prednisolone (40 mg) daily in immunosuppessive doses. The patient denied any kind of cutaneous injury prior to the onset of the lesion and any similar lesions in the past. PMID- 26380517 TI - Properties and molecular mechanisms of resveratrol: a review. AB - Resveratrol, for example widely present in the Chinese herbal medicine Polygonum cuspidatum, it is a natural phytoalexin, and has many biochemical activities, such as anti-tumor, anti-cardiovascular diseases, anti-bacterial, anti inflammatory, anti-aging and other effects. This article will concentrate on the physical and chemical properties of resveratrol, the biological and pharmacological effects for its anticancer activities. An outlook is given to the development and application prospects in this drug. PMID- 26380518 TI - Synthesis of imidazo[1,2-a]pyridines in a sequential one-pot Groebke-Blackburn modification using 2-aminopyridines, aldehydes and amines. AB - Herein we present a novel synthetic procedure for the synthesis of imidazo[1,2 a]pyridines in a modified Groebke-Blackburn fashion. In a sequential three-step one-pot protocol the commercially hardly available isocyanide-component is formed in situ using standard reagents. Cyclization to the desired products can be afforded in the same reaction mixture. The absent need of isolation of the isocyanide in this protocol eases its handling considerably and workup is only needed to finally furnish the imidazo[1,2-a]pyridines via coloumn chromatography. This protocol is a convenient way to more diverse libraries of imidazo[1,2 a]pyridines extending the functionality of the Groebke-Blackburn synthesis. PMID- 26380519 TI - Synthesis and receptor binding assay of indolin-2-one derivatives as dopamine D4 receptor ligands. AB - Five indolin-2-one derivatives bearing piperazinylbutyl side chains attached to the amide nitrogen were synthesized from 2-indolinone. 1-(4-Bromobutyl)-indolin-2 one was reacted with 1-piperazinecarboxaldehyde to form 1-(4-(4-formyl-1 piperazinyl)butyl)indolin-2-one (2). In the presence of H2SO4, the aldehyde moiety was removed from 1-(4-(4-formyl-1-piperazinyl)butyl)indolin-2-one and then 1-(4-(1-piperazinyl)butyl)indolin-2-one (3) was obtained, this compound was reacted with benzaldehyde derivatives to give the target compounds 4 a-e by N alkylation reaction. The structures of the intermediates and the target compounds were characterized by 1H NMR, ESI-MS spectra and elemental analyses. In vitro receptor binding assays at D2, D3, D4 receptor subtypes of the target compounds were performed and the five compounds showed selectivity towards D2-like receptors. Among them, 1-(4-(4-(4-hydroxybenzy)-1-piperazinyl)butyl) indolin-2 one (4c) exhibited a remarkable affinity and selectivity to D4 receptor with K(i) value of 0.5 nM. The results indicated that 1-(4-(4-(4-hydroxybenzy)-1 piperazinyl)butyl)indolin-2-one might be a potential dopamine D4 receptor ligand. PMID- 26380520 TI - LC method for determination of prasugrel and mass spectrometry detection for thermal and alkaline degradation products. AB - A stability-indicating RP-LC method for the determination of prasugrel in tablets was developed and validated. Stress testing of prasugrel was carried out in accordance with ICH guidelines, where the drug was submitted to acidic and basic hydrolysis, oxidative, thermal and photolytic conditions. Prasugrel was unstable under all the conditions and the degradations products were analyzed by HPLC-UV. Furthermore, two main degradation products found under alkaline and thermal conditions were investigated by LC-MS. Based on the fragmentation patterns, two products resulted from hydrolysis of the acetate ester moiety of prasugrel were observed. Due the chemical equilibrium, tautomerism occurs between the ketone and alcohol functions justifying the similar molecular weight and fragment pattern obtained in degradation products analysis. Successful separation was achieved on a RP-18 octadecyl silane column using acetonitrile and triethylamine 0.5% mixture (50:50, v/v) as the mobile phase at 25 degrees C. The flow rate was 1.0 mL/min and the detector wavelength was 263 nm. The method proposed in this work was successfully applied to quality control of prasugrel and contribute to stability assessment of pharmaceutical products containing this drug. PMID- 26380521 TI - Gastrointestinal symptoms after the substitution of sevelamer hydrochloride with lanthanum carbonate in Japanese patients undergoing hemodialysis. AB - Lanthanum carbonate has the same phosphorus depressant effect as the other phosphorus adsorbents, and is expected to decrease digestive symptom onset such as constipation in Japanese patients undergoing hemodialysis compared to sevelamar hydrochloride. In this study, we investigated the short- and long-term changes in digestive symptoms in these patients after substituting sevelamar hydrochloride with lanthanum carbonate. We studied 16 patients (4 men, 12 women) and evaluated their gastrointestinal symptoms before administration, at the time of administration, and 2, 4, 8, and 12 weeks after administration, using the Gastrointestinal Symptom Rating Scale. In addition, we conducted repeat evaluations 52 weeks after administration for the patients in whom lanthanum carbonate was administered continuously for 52 weeks. Fourteen (87.5%) out of the 16 patients could tolerate continuous administration for 12 weeks. The constipation score was 3.21 +/- 1.74 before administration, 2.07 +/- 0.83 2 weeks after administration, 1.76 +/- 0.83 4 weeks after administration, 1.57 +/- 0.56 8 weeks after administration, and 11.41 +/- 0.48 12 weeks after administration. The scores improved significantly 4 weeks after administration (p < 0.05) and even 12 weeks after continuous administration. Among the 16 study patients, 9 patients (1 men, 8 women) were received lanthanum carbonate continuously for 52 weeks. The constipation score was 3.74 +/- 1.92 at the start of administration, 1.37 +/- 0.56 12 weeks after administration, and 1.85 +/- 0.63 52 weeks after administration, with significant improvement even 52 weeks after administration (p < 0.05). This study shows that substituting sevelamar hydrochloride with lanthanum carbonate improves constipation symptoms in hemodialysis patients from an early stage, which indicates its usefulness in improving constipation symptoms caused by sevelamar hydrochloride. PMID- 26380522 TI - Charge heterogeneity study of a Fc-fusion protein, abatacept, using two dimensional gel electrophoresis. AB - Medicinal products obtained by recombinant DNA technology are complex molecules and demonstrate a high degree of molecular heterogeneity. Charge heterogeneity and isoform pattern of this class of medicines, are parameters important for their quality, safety, and efficacy. In this study we report the application of two-dimensional gel electrophoresis (2-D electrophoresis) for the quality assessment, identification, charge heterogeneity and isoform pattern study of recombinant protein, CTLA4-Ig (abatacept), which has been selected as an example of the drug class, known as Fc-fusion proteins. In order to achieve an efficient separation of this complex analyte,2-D electrophoresis was optimized employing different experimental conditions regarding the selection of an immobilized pH gradient (IPG), sample pretreatment, presentation and detection procedure. Experimental datadocumented that 2-D electrophoresis is a suitable method for the assessment of identity, purity, structural integrity, isoform pattern and to monitor charge heterogeneity and post-translational glycosylation of the Fc fusion protein, abatacept. PMID- 26380523 TI - Similar in vitro drug release as a surrogate of therapeutic equivalence of locally acting gastrointestinal products--what is the right in vitro method? AB - There is--apart from clinical trials--an ongoing discussion on how to demonstrate therapeutic equivalence for locally applied and locally acting products in the gastrointestinal tract. Possibly, among other alternatives, in vitro drug release models could be considered surrogates of drug release and availability at the site of action. However, to date the conditions in which in vitro models provide valid surrogates of in vivo release and availability at the site of action would have to be defined. To demonstrate the potential applicability of in vitro test methods for screening therapeutic equivalence of locally applied and locally acting gastrointestinal products and also to get an idea of which would be the right dosage form for an individual patient a series of in vitro studies was performed comparing a variety of in vitro release methods ranging from pharmacopoeial methods to "patient-specific" release methods in examining drug release of four mesalazine tablet formulations intended for local drug delivery in the gastrointestinal tract. Results from this study indicated that pharmacopoeial quality control methods are hardly applicable to predict the therapeutic equivalence of such products. Moreover, comparison of the results obtained with the different in vitro methods reveal that a prediction of the therapeutic equivalence for locally acting products in the gastrointestinal tract is unlikely based on release profiles obtained in a single drug release experiment. However, results from the study also indicated that a set of individualized biorelevant in vitro test scenarios might be very useful for both demonstrating therapeutic equivalence and selecting the appropriate drug product for a particular patient. PMID- 26380524 TI - Deleterious effect of salusin-beta in paraventricular nucleus on sympathetic activity and blood pressure via NF-kappaB signaling in a rat model of obesity hypertension. AB - The paraventricular nucleus (PVN) has been shown to play a critical role in regulating blood pressure and sympathetic activity in obesity hypertension (OH). Salusin-beta is a bioactive peptide with potential roles in mediating cardiovascular activity. The study was designed to test the hypothesis that salusin-beta in the PVN can modulate sympathetic activity and blood pressure in OH. Male Sprague-Dawley rats were used to induce OH by a 12-week feeding of a high-fat diet (42% kcal as fat). Microinjection of salusin-beta into the PVN increased the renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP) and heart rate (HR) in a dose-dependent manner, whereas salusin-beta antibody elicited significant decreases in RSNA, MAP and HR, and abolished the effects of salusin-beta only in the OH rats. As expected, the OH rats had a higher norepinephrine level, which was further increased by salusin-beta. Furthermore, salusin-beta in the PVN accelerated the nuclear translocation of the p65 subunit of nuclear factor kappa B (NF-KB) and the degradation of IKB-alpha (an endogenous inhibitor of NF-KB). Pretreatment with pyrrolidine dithiocarbamate (an exogenous inhibitor of NF-KB) decreased RSNA, MAP and HR, and abolished the effects of salusin-beta in the PVN in the OH rats. We concluded that salusin-beta in the PVN markedly increased sympathetic outflow and blood pressure in diet induced OH rats via NF-kappaB signaling. PMID- 26380525 TI - Orally co-administrated oleo-gum resin of Commiphora myrrha decreases the bioavailability of cyclosporine A in rats. AB - Cyclosporine A is a narrow therapeutic indexed immunosuppressant used after organ transplantation. Several herbs have been reported to alter its pharmacokinetics. Myrrh, dried oleogum resin obtained from Commiphora myrrha (Burseraceae) has been used for many common ailments. The present study was carried out to investigate the effect of myrrh on the pharmacokinetics of cyclosporine A. The rats of the control group received 60 mg/kg, p.o. cyclosporine A, and blood samples were collected at predetermined time intervals. Rats of the test group were treated with an aqueous suspension of myrrh (380 mg/kg p.o.) for eight days and on 8th day a single dose of cyclosporine A was administered to the treated group after 1 h of myrrh administration. Blood samples were drawn at predetermined time points and the drug was analyzed in whole blood by using H-Class UPLC-TQD. Pharmacokinetic profiles of control and test group were compared. Statistically significant differences were observed between the pharmacokinetic parameters of control and treated groups. In the myrrh treated group, the AUC(0-t) and C(max) of cyclosporine A was decreased by about 45% and 48%, respectively. The time to reach maximum concentration (T(max)) remained almost unchanged in both groups. Results indicated that the bioavailability of cyclosporine A was reduced by about 45% when co-administered with myrrh. This observation suggests that concurrent consumption of myrrh and cyclosporine A should be avoided. To confirm the clinical relevance of these findings, P-gp and CYP3A based molecular investigations can be performed along with a well-planned clinical study. PMID- 26380526 TI - Phenolics from Caesalpinia ferrea Mart.: antioxidant, cytotoxic and hypolipidemic activity. AB - Nine phenolics were isolated from the aqueous ethanol extract of the leaves of Caesalpinia ferrea. The isolates were characterized for the first time from that plant. The structures of all isolates (1-9) were elucidated by conventional methods, spectroscopic analysis, including 1 D and 2D NMR, and by HR-ESIMS as well. The antioxidant capacities using the ORAC method and the cytotoxic activity using the neutral red assay (NRU) for that extract and three major isolates have been evaluated. In addition, the hypolipidemic activity (in vitro and in vivo) of the extract has been assessed. PMID- 26380527 TI - The potential role of clinical pharmacists in elderly patients during hospital admission. AB - The aim of this study was to show the potential impact of services directed by clinical pharmacists, including medication reconciliation and medication review, on the hospital admission process for elderly patients. This study was conducted in an internal medicine ward between April 24 and July 25, 2014. Patients hospitalized due to any reason were eligible if they were 65 years or older and regularly used at least one medication at home. The clinical pharmacist evaluated potentially inappropriate medications (PIM), medication related problems (MRPs) and medication discrepancies at the time when these eligible elderly patients were admitted to the hospital. The physician acceptance rate as related the clinical pharmacist's recommendation was evaluated retrospectively. A total of 133 elderly patients (mean age 76.62 +/- 8.12 years old; 70 female) were included in the study. Out of 394 medication discrepancies, 88.32% were found to be unintended discrepancies among 111 elderly patients upon hospital admission. PIM was found in 19.55% of these cases. A total of 396 MRPs among 115 patients were identified, with the most common being that the drug had not been taken/administered at all. The doctor acceptance rate of the clinical pharmacist's recommendation was found to be 85.60%. In conclusion, it was found that medication related problems and inappropriate medication utilization at admission could be prevented at a high rate of success by clinical pharmacist driven medication reconciliation and medication review services. PMID- 26380528 TI - MIGRATION PATTERNS, USE OF STOPOVER AREAS, AND AUSTRAL SUMMER MOVEMENTS OF SWAINSON'S HAWKS. AB - From 1995-1998, we tracked movements of adult Swainson's Hawks (Buteo swainsoni) using satellite telemetry to characterize migration, important stopover areas, and austral summer movements. We tagged 46 hawks from July - September on their nesting grounds in seven U.S. states and two Canadian provinces. Swainson's Hawks basically followed three routes south on a broad front, converged along the east coast of central Mexico, and followed a concentrated corridor to a communal austral summer area in central Argentina. North of 20 degrees N, southward and northward tracks differed little for individuals from east of the Continental Divide but differed greatly (up to 1700 km) for individuals from west of the Continental Divide. Hawks left the breeding grounds mid-August to mid-October; departure dates did not differ by location, year, or sex. South migration lasted 42 to 98 days, and north migration took 51 to 82 days. On south migration, 36% of the Swainson's Hawks departed the nesting grounds nearly 3 weeks earlier than the other radio marked hawks and made stopovers 9.0 - 26.0 days long in seven separate areas, mainly in the southern Great Plains, southern Arizona and New Mexico, and north-central Mexico. The austral period lasted 76 to 128 days. All Swainson's Hawks used a core area in central Argentina within 23% of the 738800 km2 austral summer range where they frequently moved long distances (up to 1600 km). Conservation of Swainson's Hawks must be an international effort that considers habitats used during nesting and non-nesting seasons including migration stopovers. PMID- 26380529 TI - Helmet-Cam: tool for assessing miners' respirable dust exposure. AB - Video technology coupled with datalogging exposure monitors have been used to evaluate worker exposure to different types of contaminants. However, previous application of this technology used a stationary video camera to record the worker's activity while the worker wore some type of contaminant monitor. These techniques are not applicable to mobile workers in the mining industry because of their need to move around the operation while performing their duties. The Helmet Cam is a recently developed exposure assessment tool that integrates a person wearable video recorder with a datalogging dust monitor. These are worn by the miner in a backpack, safety belt or safety vest to identify areas or job tasks of elevated exposure. After a miner performs his or her job while wearing the unit, the video and dust exposure data files are downloaded to a computer and then merged together through a NIOSH-developed computer software program called Enhanced Video Analysis of Dust Exposure (EVADE). By providing synchronized playback of the merged video footage and dust exposure data, the EVADE software allows for the assessment and identification of key work areas and processes, as well as work tasks that significantly impact a worker's personal respirable dust exposure. The Helmet-Cam technology has been tested at a number of metal/nonmetal mining operations and has proven to be a valuable assessment tool. Mining companies wishing to use this technique can purchase a commercially available video camera and an instantaneous dust monitor to obtain the necessary data, and the NIOSH-developed EVADE software will be available for download at no cost on the NIOSH website. PMID- 26380530 TI - Concentrating childhood cancer treatment in the Netherlands. AB - Paediatric tertiary care is highly centralized in the Netherlands. The country is small (16 million inhabitants, overall unemployment rates were approximately 7 % in 2014, while young adult (< 25 years) unemployment rates were 12 %) with the majority of the population living in Amsterdam and Rotterdam and their neighbouring cities/villages. There are 90 hospitals taking care for children in the Netherlands. Specific types of highly specialized care, such as transplantation, are provided in a maximum of three centres (kidney transplants in 3, bone marrow tranplants in 2, liver transplants in only one center), while neonatal intensive care is offered in 10 hospitals. Recently, patients with solid tumours in the thorax and abdomen were concentrated in a single centre with five university centres who provide care during the less intensive part of the treatment (in shared care). Similar changes are planned for congenital surgery, aiming for two such centres in the Netherlands. The general view of the Dutch Paediatric Association underscores the need for centralisation, while high-level care should be guaranteed at those hospitals where no specialized centre is present. PMID- 26380531 TI - Nonideal Transport of Contaminants in Heterogeneous Porous Media: 11. Testing the Experiment Condition Dependency of the Continuous-Distribution Rate Model for Sorption-Desorption. AB - A series of miscible-displacement experiments was conducted to examine the impact of experiment conditions (detection limit, input-pulse size, input concentration, pore-water velocity, contact time) on the performance of a mathematical solute transport model incorporating nonlinear, rate-limited sorption/desorption described by a continuous-distribution reaction function. Effluent solute concentrations were monitored over a range of approximately seven orders of magnitude, allowing characterization of asymptotic tailing phenomenon. The model successfully simulated the extensive elution tailing observed for the measured data. Values for the mean desorption rate coefficient (ln k2) and the variance of ln k2 were obtained through calibration of the model to measured data. Similar parameter values were obtained for experiments with different input-pulse size, input concentration, pore-water velocity, contact time. This suggests that the model provided a robust representation of sorption-desorption for this system tested. The impact of analytical detection limit was examined by calibrating the model to subsets of the breakthrough curves wherein the extent of the elution tail was artificially reduced to mimic a poorer detection limit. The parameters varied as a function of the extent of elution tail used for the calibrations, indicating the importance of measuring as full an extent of the tail as possible. PMID- 26380532 TI - Using a Gas-Phase Tracer Test to Characterize the Impact of Landfill Gas Generation on Advective-Dispersive Transport of VOCs in the Vadose Zone. AB - A gas-phase tracer test (GTT) was conducted at a landfill in Tucson, AZ, to help elucidate the impact of landfill gas generation on the transport and fate of chlorinated aliphatic volatile organic contaminants (VOCs). Sulfur hexafluoride (SF6) was used as the non-reactive gas tracer. Gas samples were collected from a multiport monitoring well located 15.2 m from the injection well, and analyzed for SF6, CH4, CO2, and VOCs. The travel times determined for SF6 from the tracer test are approximately two to ten times smaller than estimated travel times that incorporate transport by only gas-phase diffusion. In addition, significant concentrations of CH4 and CO2 were measured, indicating production of landfill gas. Based on these results, it is hypothesized that the enhanced rates of transport observed for SF6 are caused by advective transport associated with landfill gas generation. The rates of transport varied vertically, which is attributed to multiple factors including spatial variability of water content, refuse mass, refuse permeability, and gas generation. PMID- 26380533 TI - The effects of strength-based versus deficit-based self-regulated learning strategies on students' effort intentions. AB - In two randomized experiments, one conducted online (n = 174) and one in the classroom (n = 267), we tested the effects of two types of self-regulated learning (SRL) strategies on students' intentions to put effort into professional development activities: strength-based SRL strategies (i.e., identifying perceived relative strengths and, subsequently, selecting professional development activities to further improve those strengths) versus deficit-based SRL strategies (i.e., identifying perceived relative shortcomings and, subsequently, selecting professional development activities to improve those shortcomings). Across both studies, analysis of variance revealed that, relative to students who used deficit-based SRL strategies, students who used strength based SRL strategies were higher in perceived competence, intrinsic motivation, and effort intentions. Moreover, the results of multi-mediator analysis and structural equation modeling supported the hypothesis that the effect of strength based versus deficit-based SRL strategies on students' effort intentions was sequentially mediated by perceived competence and intrinsic motivation. Implications for the application of self-regulated learning strategies in the context of professional self-development are discussed. PMID- 26380534 TI - The role of implicit affective responses and trait self-control in ego resource management. AB - Exertion of self-control requires reliance on ego resources. Impaired performance typically results once those resources have been depleted by previous use. Yet the mechanism behind the depletion processes is little understood. Beliefs, motivation, and physiological changes have been implicated, yet the source behind these remains unknown. We propose that implicit may form the fundamental building blocks that these processes rely upon to operate. Implicit affective responses to energy may trigger management of ego resources after depletion. Findings suggest that inhibitory trait self-control may interact with the depletion effect, indicating the importance of taking individual differences in chronic availability of ego-resources into account. After depletion, individuals high in trait self-control may be less motivated to conserve remaining resources than those low in self-control. This mechanism may also help explain the conservation of resources observed when expecting multiple tasks requiring self-control. PMID- 26380535 TI - Social networks and life satisfaction: The interplay of network density and regulatory focus. AB - We propose that an individual's regulatory focus moderates the significant role social network density-the degree of interconnectedness among a person's social contacts-plays in shaping life satisfaction. Evidence from Study 1 indicates that participants with high prevention effectiveness reported higher life satisfaction when they were embedded in a high-density network, whereas participants with low promotion effectiveness reported lower life satisfaction when they were embedded in a low-density network. Study 2 further specifies the underlying mechanism, namely that participants with high prevention effectiveness are more likely to obtain support for meeting obligations and responsibilities when they are embedded in a high-density network, whereas participants with low promotion effectiveness suffer from the support for creative inspiration and personal development in a low-density network (by highlighting their promotion failure). Implications for studying the interplay between social networks and individuals' self-regulatory motives are discussed. PMID- 26380536 TI - 3D Cine Magnetic Resonance Imaging of Rat Lung ARDS using Gradient-modulated SWIFT with Retrospective Respiratory Gating. AB - SWeep Imaging with Fourier Transformation (SWIFT) with gradient modulation and DC navigator retrospective gating is introduced as a 3D cine magnetic resonance imaging (MRI) method for the lung. The quasi-simultaneous excitation and acquisition in SWIFT enabled extremely high sensitivity to the fast-decaying parenchymal signals (TE=~4 MUs), which are invisible with conventional MRI techniques. Based on respiratory motion information extracted from DC navigator signals, the SWIFT data were reconstructed to 3D cine images with 16 respiratory phases. To test the capability of the proposed technique, rats exposed to > 95% O2 for 60 hours for induction of acute respiratory distress syndrome (ARDS), were imaged and compared with normal rat lungs (N=7 and 5 for ARDS and normal group, respectively). SWIFT images showed lung tissue density difference along the gravity direction. In the cine SWIFT images, parenchymal signal drop at the inhalation phase was consistently observed for both normal and ARDS rats due to inflation of the lung (i.e. decrease of the proton density), but the drop was less for ARDS rats. Depending on the respiration phase and lung region, the lungs from the ARDS rats showed 1-24% higher parenchymal signal intensities relative to the normal rat lungs, which would be mainly from accumulation of extravascular water (EVLW). Those results demonstrate that SWIFT has high enough sensitivity for detecting the lung proton density changes due to gravity, different respiration phases and accumulation of EVLW in the rat ARDS lungs. PMID- 26380537 TI - What underlies waves of agitation in starling flocks. AB - Fast transfer of information in groups can have survival value. An example is the so-called wave of agitation observed in groups of animals of several taxa under attack. It has been shown to reduce predator success. It usually involves the repetition of a manoeuvre throughout the group, transmitting the information of the attack quickly, faster than the group moves itself. The specific manoeuvre underlying a wave is typically known, but not so in starlings (Sturnus vulgaris). Although waves of agitation in starling flocks have been suggested to reflect density waves, exact escape manoeuvres cannot be distinguished because flocks are spatially too far away. Therefore, waves may also reflect orientation waves (due to escape by rolling). In the present study, we investigate this issue in a computational model, StarDisplay. We use this model because its flocks have been shown to resemble starling flocks in many traits. In the model, we show that agitation waves result from changes in orientation rather than in density. They resemble empirical data both qualitatively in visual appearance and quantitatively in wave speed. In the model, local interactions with only two to seven closest neighbours suffice to generate empirical wave speed. Wave speed increases with the number of neighbours mimicked or repeated from and the distance to them. It decreases with reaction time and with time to identify the escape manoeuvre of others and is not affected by flock size. Our findings can be used as predictions for empirical studies. PMID- 26380538 TI - Nanoparticles functionalized with collagenase exhibit improved tumor accumulation in a murine xenograft model. AB - Nanoparticles have garnered widespread interest for both the imaging and treatment of cancer due to their unique and tunable pharmacokinetics and their ability to carry a high payload of diverse compounds. However, despite these favorable attributes, the extent of tumor accumulation can be severely restricted due to the dense stroma surrounding the often-permeable blood vessel wall and high intratumoral pressure. In this study, we investigated whether modifying the surface of pegylated gold nanoparticles (AuNPs) with collagenase could improve the accumulation of nanoparticles within a murine tumor xenograft. It was determined that collagenase remains active after surface conjugation and the presence of collagenase has no measureable effect on cell proliferation in vitro. Following intravenous injection, the largest fractions of collagenase-labeled AuNPs were found in the liver and spleen. Histological analysis revealed no signs of toxicity in either of these organs. Blood chemistry revealed normal levels of liver enzymes, but a slightly elevated level of total bilirubin. Within the tumor, AuNPs labeled with collagenase exhibited a 35% increase in accumulation compared with unlabeled AuNPs. Therefore, these studies provide preliminary evidence that the functionalization of nanoparticles with collagenase represent an effective and safe approach to improve tumor accumulation. PMID- 26380539 TI - Disparities in Survival Patterns for Oral and Pharyngeal Cancer in Florida: Can We Do Anything about It? PMID- 26380540 TI - Development and application of an eDNA method to detect and quantify a pathogenic parasite in aquatic ecosystems. AB - Approaches based on organismal DNA found in the environment (eDNA) have become increasingly utilized for ecological studies and biodiversity inventories as an alternative to traditional field survey methods. Such DNA-based techniques have largely been used to establish the presence of free-living organisms, but have much potential for detecting and quantifying infectious agents in the environment, which is necessary to evaluate disease risk. We developed an eDNA method to examine the distribution and abundance of the trematode Ribeiroia ondatrae, a pathogenic parasite known to cause malformations in North American amphibians. In addition to comparing this eDNA approach to classical host necropsy, we examined the detectability of R. ondatrae in water samples subject to different degradation conditions (time and temperature). Our test exhibited high specificity and sensitivity to R. ondatrae, capable of detecting as little as 14 fg (femtograms) of this parasite's DNA (1/2500th of a single infectious stage) from field water samples. Compared to our results from amphibian host necropsy, quantitative PCR was -90% concordant with respect to R. ondatrae detection from 15 field sites and was also a significant predictor of host infection abundance. DNA was still detectable in lab samples after 21 days at 25 degrees C, indicating that our method is robust to field conditions. By comparing the advantages and disadvantages of eDNA vs. traditional survey methods for determining pathogen presence and abundance in the field, we found that the lower cost and effort associated with eDNA approaches provide many advantages. The development of alternative tools is critical for disease ecology, as wildlife management and conservation efforts require reliable establishment and monitoring of pathogens. PMID- 26380541 TI - Psychometric Evaluation of the Symptoms and Functioning Severity Scale (SFSS) Short Forms with Out-of-Home Care Youth. AB - BACKGROUND: There is a need for brief progress monitoring measures of behavioral and emotional symptoms for youth in out-of-home care. The Symptoms and Functioning Severity Scale (SFSS; Bickman et al., 2010) is one measure that has clinician and youth short forms (SFSS-SFs); however, the psychometric soundness of the SFSS-SFs with youth in out-of-home care has yet to be examined. OBJECTIVE: The objective was to determine if the psychometric characteristics of the clinician and youth SFSS-SFs are viable for use in out-of-home care programs. METHODS: The participants included 143 youth receiving residential treatment and 52 direct care residential staff. The current study assessed internal consistency and alternate forms reliability for SFSS-SFs for youth in a residential care setting. Further, a binary classification test was completed to determine if the SFSS-SFs similarly classified youth as the SFSS full version for low- and elevated-severity. RESULTS: The internal consistency for the clinician and youth SFSS-SFs was adequate (alpha = .75 to .82) as was the parallel forms reliability (r = .85 to .97). The sensitivity (0.80 to 0.95), specificity (0.88 to 0.97), and overall accuracy (0.89 to 0.93) for differentiating low and elevated symptom severity was acceptable. CONCLUSIONS: The clinician and youth SFSS-SFs have acceptable psychometrics and may be beneficial for progress monitoring and additional research should clarify their potential for progress monitoring of youth in out-of-home programs. PMID- 26380542 TI - Cardiomyopathies in Noonan syndrome and the other RASopathies. AB - Noonan syndrome and related disorders (Noonan syndrome with multiple lentigines, Costello syndrome, cardiofaciocutaneous syndrome, Noonan syndrome with loose anagen hair, and other related traits) are autosomal dominant traits. Mutations causing these disorders alter proteins relevant for signaling through RAS. Thus, these traits are now collectively called the RASopathies. While the RASopathies have pleiomorphic features, this review will focus on the hypertrophic cardiomyopathy observed in varying percentages of all of these traits. In addition, inherited abnormalities in one pathway gene, RAF1, cause pediatric onset dilated cardiomyopathy. The pathogeneses for the RASopathy-associated cardiomyopathies are being elucidated, principally using animal models, leading to genotype-specific insights into how signal transduction is perturbed. Based on those findings, small molecule therapies seem possible for RASopathy-associated cardiomyopathies. PMID- 26380544 TI - Tendon-Driven Continuum Robot for Endoscopic Surgery: Preclinical Development and Validation of a Tension Propagation Model. AB - In this paper, we present a tendon-driven continuum robot for endoscopic surgery. The robot has two sections for articulation actuated by tendon wires. By actuating the two sections independently, the robot can generate a variety of tip positions while maintaining the tip direction. This feature offers more flexibility in positioning the tip for large viewing angles of up to 180 degrees than does a conventional endoscope. To accurately estimate the tip position at large viewing angles, we employed kinematic mapping with a tension propagation model including friction between the tendon wires and the robot body. In a simulation study using this kinematic-mapping, the two-section robot at a target scale (outer diameter 1.7 mm and length 60 mm) produced a variety of tip positions within 50-mm ranges at the 180 degrees -angle view. In the experimental validation, a 10:1 scale prototype performed three salient postures with different tip positions at the 180 degrees -angle view. The proposed forward kinematic mapping (FKM) predicted the tip position within a tip-to-tip error of 6 mm over the 208-mm articulating length. The tip-to-tip error by FKM was significantly less than the one by conventional piecewise-constant-curvature approximation (PCCA) (FKM: 5.9 +/- 2.9 mm vs. PCCA: 23.7 +/- 3.6 mm, n=15, P < 0.01). PMID- 26380543 TI - Toward Personalized Medicine: Does Genetic Diagnosis of Pediatric Cardiomyopathy Influence Patient Management? AB - A goal of personalized medicine is to provide increasingly sophisticated, individualized approaches to management and therapy for disease. Genetics is the engine that drives personalized medicine, holding the promise of therapeutics directed toward the unique needs of each patient. The 3rd International Conference on Cardiomyopathy in Children provided a forum to discuss the current status of personalized approaches to diagnosis, management, and therapy in the pediatric cardiomyopathy population. This review will focus on the importance of genetic diagnosis in this population as a necessary first step toward understanding the best approach to management and influencing disease outcome. The genetic heterogeneity of cardiomyopathy in children, the implications of specific genotypes, the ability to risk stratify based on genotype, and the impact on cascade screening in family members will be discussed. PMID- 26380545 TI - ASSESSING THE POTENTIAL EFFECTS OF FUNGICIDES ON NONTARGET GUT FUNGI (TRICHOMYCETES) AND THEIR ASSOCIATED LARVAL BLACK FLY HOSTS. AB - Fungicides are moderately hydrophobic and have been detected in water and sediment, particularly in agricultural watersheds, but typically are not included in routine water quality monitoring efforts. This is despite their widespread use and frequent application to combat fungal pathogens. Whereas the efficacy of these compounds on fungal pathogens is well documented, little is known about their effects on nontarget fungi. This pilot study, a field survey in southwestern Idaho from April to December 2010 on four streams with varying pesticide inputs (two agricultural and two reference sites), was conducted to assess nontarget impact of fungicides on gut fungi, or trichomycetes. Tissues of larval black flies (Diptera: Simuliidae), hosts of gut fungi, were analyzed for pesticide accumulation. Fungicides were detected in hosts from streams within agricultural watersheds but were not detected in hosts from reference streams. Gut fungi from agricultural sites exhibited decreased percent infestation, density within the gut, and sporulation, and black fly tissues had elevated pesticide concentrations. Differences observed between the sites demonstrate a potential effect on this symbiotic system. Future research is needed to parse out the details of the complex biotic and abiotic relationships; however, these preliminary results indicate that impacts to nontarget organisms could have far reaching consequences within aquatic ecosystems. PMID- 26380546 TI - In Silico Characterization of Functional Divergence of Two Cathelicidin Variants in Indian Sheep. AB - The present work focuses on the in silico characterization of functional divergence of two ovine cathelicidin coding sequence (cds) variants (ie, Cath1 and Cath2) of Indian sheep. Overlapping partial cds of both the cathelicidin variants were cloned in pJet1.2/blunt vector and sequenced. Evolutionary analysis of the Cath2 and Cath1 indicated that the mammalian cathelicidins clustered separately from avian fowlicidins. The avian fowlicidins, which are very different from mammalian cathelicidins (Caths), clearly displayed signatures of purifying selection. The pairwise sequence alignments of translated amino acid sequences of these two sheep cathelicidins showed gaps in the antimicrobial domain of Cath1 variant; however, the amino terminal cathelin regions of both the Caths were conserved. Amino acid sequence analysis of full-length cathelicidins available at public database revealed that Cath1, Cath2, and Cath7 of different ruminant species (including our Cath1 and Cath2 variants) formed individual clads, suggesting that these types have evolved to target specific types of microbes. In silico analysis of Cath1 and Cath2 peptide sequences indicated that the C-terminal antimicrobial peptide domain of Cath2 is more immunogenic than that of the ovine Cath1 due to its higher positive antigenic index, making Cath1 a promising antigen for production of monoclonal antibodies. PMID- 26380547 TI - Preprocessing Steps for Agilent MicroRNA Arrays: Does the Order Matter? AB - MOTIVATION/BACKGROUND: Previous publications on microarray preprocessing mostly focused on method development or comparison for an individual preprocessing step. Very few, if any, focused on recommending an effective ordering of the preprocessing steps, in particular, normalization in relationship to log transformation and probe set summarization. In this study, we aim to study how the relative ordering of the preprocessing steps influences differential expression analysis for Agilent microRNA array data. METHODS: A set of 192 untreated primary gynecologic tumor samples (96 endometrial tumors and 96 ovarian tumors) were collected at Memorial Sloan Kettering Cancer Center during the period of 2000-2012. From this same sample set, two datasets were generated: one dataset had no confounding array effects by experimental design and served as the benchmark, and another dataset exhibited array effects and served as the test data. We preprocessed our test dataset using different orderings between the following three steps: quantile normalization, log transformation, and median summarization. Differential expression analysis was performed on each preprocessed test dataset, and the results were compared against the results from the benchmark dataset. True positive rate, false positive rate, and false discovery rate were used to assess the effectiveness of the orderings. RESULTS: The ordering of log transformation, quantile normalization (on probe-level data), and median summarization slightly outperforms the other orderings. CONCLUSION: Our results ease the anxiety over the uncertain effect that the orderings could have on the analysis of Agilent microRNA array data. PMID- 26380548 TI - Computer Simulation, Bioinformatics, and Statistical Analysis of Cancer Data and Processes. PMID- 26380549 TI - CoGNaC: A Chaste Plugin for the Multiscale Simulation of Gene Regulatory Networks Driving the Spatial Dynamics of Tissues and Cancer. AB - We introduce a Chaste plugin for the generation and the simulation of Gene Regulatory Networks (GRNs) in multiscale models of multicellular systems. Chaste is a widely used and versatile computational framework for the multiscale modeling and simulation of multicellular biological systems. The plugin, named CoGNaC (Chaste and Gene Networks for Cancer), allows the linking of the regulatory dynamics to key properties of the cell cycle and of the differentiation process in populations of cells, which can subsequently be modeled using different spatial modeling scenarios. The approach of CoGNaC focuses on the emergent dynamical behavior of gene networks, in terms of gene activation patterns characterizing the different cellular phenotypes of real cells and, especially, on the overall robustness to perturbations and biological noise. The integration of this approach within Chaste's modular simulation framework provides a powerful tool to model multicellular systems, possibly allowing for the formulation of novel hypotheses on gene regulation, cell differentiation, and, in particular, cancer emergence and development. In order to demonstrate the usefulness of CoGNaC over a range of modeling paradigms, two example applications are presented. The first of these concerns the characterization of the gene activation patterns of human T-helper cells. The second example is a multiscale simulation of a simplified intestinal crypt, in which, given certain conditions, tumor cells can emerge and colonize the tissue. PMID- 26380550 TI - Development and Validation of a Clinical Risk-Assessment Tool Predictive of All Cause Mortality. AB - In clinical settings, the diagnosis of medical conditions is often aided by measurement of various serum biomarkers through the use of laboratory tests. These biomarkers provide information about different aspects of a patient's health and overall function of multiple organ systems. We have developed a statistical procedure that condenses the information from a variety of health biomarkers into a composite index, which could be used as a risk score for predicting all-cause mortality. It could also be viewed as a holistic measure of overall physiological health status. This health status metric is computed as a function of standardized values of each biomarker measurement, weighted according to their empirically determined relative strength of association with mortality. The underlying risk model was developed using the biomonitoring and mortality data of a large sample of US residents obtained from the National Health and Nutrition Examination Survey (NHANES) and the National Death Index (NDI). Biomarker concentration levels were standardized using spline-based Cox regression models, and optimization algorithms were used to estimate the weights. The predictive accuracy of the tool was optimized by bootstrap aggregation. We also demonstrate how stacked generalization, a machine learning technique, can be used for further enhancement of the prediction power. The index was shown to be highly predictive of all-cause mortality and long-term outcomes for specific health conditions. It also exhibited a robust association with concurrent chronic conditions, recent hospital utilization, and current health status as assessed by self-rated health. PMID- 26380551 TI - Clinical Outcomes with First-line Endocrine Therapy or Chemotherapy in Postmenopausal HR+/HER2- Metastatic Breast Cancer. AB - OBJECTIVE: To describe patient profiles and clinical outcomes associated with first-line endocrine monotherapy (ET) and chemotherapy (CT) for postmenopausal HR+/HER2- metastatic breast cancer (mBC) patients. METHODS: This is a retrospective chart review of 139 postmenopausal HR+/HER2- mBC patients initiating first-line ET monotherapy or CT. Overall survival (OS) was described using Kaplan-Meier curves. Exploratory comparative proportional hazards regression was conducted. RESULTS: Patients on first-line CT had significantly more frequent liver metastases than patients on first-line ET monotherapy at baseline. The median OS was 35.5 months [95% confidence interval (CI), 22.7-41.2 months] for patients on first-line ET monotherapy and 22.2 months (95% CI, 13.6 25.9 months) for those on first-line CT (P = 0.021). Adjusting for baseline characteristics, the OS between first-line ET monotherapy and CT was not significantly different. CONCLUSIONS: Patients who were prescribed CT as first line treatment had evidence of more advanced disease at baseline and shorter OS than those who received ET monotherapy as first-line treatment, suggesting a need for additional safe and effective treatment options for these patients. PMID- 26380552 TI - Targeting Breast Cancer Metastasis. AB - Metastasis is the leading cause of breast cancer-associated deaths. Despite the significant improvement in current therapies in extending patient life, 30-40% of patients may eventually suffer from distant relapse and succumb to the disease. Consequently, a deeper understanding of the metastasis biology is key to developing better treatment strategies and achieving long-lasting therapeutic efficacies against breast cancer. This review covers recent breakthroughs in the discovery of various metastatic traits that contribute to the metastasis cascade of breast cancer, which may provide novel avenues for therapeutic targeting. PMID- 26380553 TI - Single and Multiple Gene Manipulations in Mouse Models of Human Cancer. AB - Mouse models of human cancer play a critical role in understanding the molecular and cellular mechanisms of tumorigenesis. Advances continue to be made in modeling human disease in a mouse, though the relevance of a mouse model often relies on how closely it is able to mimic the histologic, molecular, and physiologic characteristics of the respective human cancer. A classic use of a genetically engineered mouse in studying cancer is through the overexpression or deletion of a gene. However, the manipulation of a single gene often falls short of mimicking all the characteristics of the carcinoma in humans; thus a multiple gene approach is needed. Here we review genetic mouse models of cancers and their abilities to recapitulate human carcinoma with single versus combinatorial approaches with genes commonly involved in cancer. PMID- 26380555 TI - Emerging and Evolving Ovarian Cancer Animal Models. AB - Ovarian cancer (OC) is the leading cause of death from a gynecological malignancy in the United States. By the time a woman is diagnosed with OC, the tumor has usually metastasized. Mouse models that are used to recapitulate different aspects of human OC have been evolving for nearly 40 years. Xenograft studies in immunocompromised and immunocompetent mice have enhanced our knowledge of metastasis and immune cell involvement in cancer. Patient-derived xenografts (PDXs) can accurately reflect metastasis, response to therapy, and diverse genetics found in patients. Additionally, multiple genetically engineered mouse models have increased our understanding of possible tissues of origin for OC and what role individual mutations play in establishing ovarian tumors. Many of these models are used to test novel therapeutics. As no single model perfectly copies the human disease, we can use a variety of OC animal models in hypothesis testing that will lead to novel treatment options. The goal of this review is to provide an overview of the utility of different mouse models in the study of OC and their suitability for cancer research. PMID- 26380554 TI - Skin Carcinogenesis Studies Using Mouse Models with Altered Polyamines. AB - Nonmelanoma skin cancer (NMSC) is a major health concern worldwide. With increasing numbers in high-risk groups such as organ transplant recipients and patients taking photosensitizing medications, the incidence of NMSC continues to rise. Mouse models of NMSC allow us to better understand the molecular signaling cascades involved in skin tumor development in order to identify novel therapeutic strategies. Here we review the models designed to determine the role of the polyamines in NMSC development and maintenance. Elevated polyamines are absolutely required for tumor growth, and dysregulation of their biosynthetic and catabolic enzymes has been observed in NMSC. Studies using mice with genetic alterations in epidermal polyamines suggest that they play key roles in tumor promotion and epithelial cell survival pathways, and recent clinical trials indicate that pharmacological inhibitors of polyamine metabolism show promise in individuals at high risk for NMSC. PMID- 26380557 TI - Impaired Spatial Learning Memory after Isoflurane Anesthesia or Appendectomy in Aged Mice is Associated with Microglia Activation. AB - Postoperative cognitive dysfunction (POCD) has been one of the most common problems in elderly patients following surgery. But the specific mechanism of POCD is still not clear. To further understand the reason of these postoperative behavioral deficits, we evaluated the spatial learning memory of both adult (3 months) and aged (18 months) male mice, 3 or 28 days after isoflurane (Iso) exposure for two hours or appendectomy (App). Hippocampal microglia activation and IL-1beta, TNF-alpha, and IFN-gamma expression were also evaluated at day 3, day 14 and day 28 after Iso exposure or appendectomy. Results showed that spatial learning memory of aged, but not adult, mice was impaired after Iso exposure or appendectomy, accompanied with more hippocampal microglia activation and IL 1beta, TNF-alpha, and IFN-gamma overexpression. These findings suggest that the cognitive deficits of elderly patients who have undergone surgeries are quite possibly caused by hippocampal microglia overactivation and the subsequent inflammation. PMID- 26380556 TI - Esophageal Cancer: Insights From Mouse Models. AB - Esophageal cancer is the eighth leading cause of cancer and the sixth most common cause of cancer-related death worldwide. Despite recent advances in the development of surgical techniques in combination with the use of radiotherapy and chemotherapy, the prognosis for esophageal cancer remains poor. The cellular and molecular mechanisms that drive the pathogenesis of esophageal cancer are still poorly understood. Hence, understanding these mechanisms is crucial to improving outcomes for patients with esophageal cancer. Mouse models constitute valuable tools for modeling human cancers and for the preclinical testing of therapeutic strategies in a manner not possible in human subjects. Mice are excellent models for studying human cancers because they are similar to humans at the physiological and molecular levels and because they have a shorter gestation time and life cycle. Moreover, a wide range of well-developed technologies for introducing genetic modifications into mice are currently available. In this review, we describe how different mouse models are used to study esophageal cancer. PMID- 26380558 TI - Effect of Vitamin E Administration on Learning of the Young Male Rats. AB - The effect of vitamin E intake on spatial learning and working memory performances of young rats has been investigated in the Morris water maze and locomotor activity has been assessed by an open-field test. A total of 45 young male Wistar albino rats aged two months were divided into three equal groups: control, olive oil, and vitamin E groups. These groups were treated for 30 days with a once daily intraperitoneal injection. The rats were then tested for their ability to find the location of the platform (spatial learning). The results revealed that there was no statistically significant difference between the time spent to find the platform and the time spent in half area of the tank, including the platform among the group, while the time spent to find the platform was found to have increased from the first day to the fourth day in all the groups. In the open-field test, the locomotor activity quite significantly increased in the peripheral area in the olive oil group. The supplementation with vitamin E for a short period had not improved the learning performance of the healthy young rats. It was concluded that the beneficial effect of vitamin E intake on learning is related to the beginning time and the duration of vitamin E intake. PMID- 26380559 TI - Computational Shape Models Characterize Shape Change of the Left Atrium in Atrial Fibrillation. AB - Shape change of the left atrium (LA) and LA appendage in atrial fibrillation (AF) patients is hypothesized to be linked to AF pathology and to play a role in thrombogenesis; however, many aspects of shape variation in the heart are poorly understood. To date, studies of the LA shape in AF have been limited to empirical observation and summary metrics, such as volume and its likeness to a sphere. This paper describes a more comprehensive approach to the study of the LA shape through the use of computationally derived statistical shape models. We describe practical approaches that we have developed to extract shape parameters automatically from the three-dimensional MR images of the patient. From these images and our techniques, we can produce a more comprehensive description of LA geometric variability than that has been previously possible. We present the methodology and results from two examples of specific analyses using shape models: (1) we describe statistically significant group differences between the normal control and AF patient populations (n = 137) and (2) we describe characteristic shapes of the LA appendage that are associated with the risk of thrombogenesis determined by transesophageal echocardiography (n = 203). PMID- 26380560 TI - Secondary Sclerosing Cholangitis and Hodgkin's Lymphoma. AB - CONTEXT: Liver damage is relatively common in patients affected by HL, but paraneoplastic cholestasis is an uncommon presenting symptom in HL. CASE REPORT: We report the case of a 38-year-old man who came to our hospital with jaundice, pruritis, nausea, vomiting, weight loss, and recurrent episodes of fever without any hepatosplenomegaly or lymphadenopathy. Laboratory findings showed abnormal liver functioning with mixed hepatocellular and cholestatic patterns. Sonographic evaluation of the biliary tract was normal. We ruled out viral infections, autoimmune process, and hemochromatosis. The patient was put on ursobile and NAC (N-acetyl-systeine) and prednisolone treatment. In magnetic resonance cholangiopancreatography examination, there were multiple strictures in the intrahepatic and extrahepatic bile ducts with mild dilatation. Histologic finding of liver biopsy was compatible with sclerosing cholangitis or drug-induced cholestasis. General condition and laboratory examination results of the patient became better, but we found lymph-adenopathy on monthly follow-up examination. Histological finding of the lymph node was compatible with HL. CONCLUSION: This report emphasizes that HL can be presented with different paraneoplastic symptoms and that one of them is secondary sclerosing cholangitis. It has better prognosis than vanishing bile duct syndrome, and perhaps steroid treatment can be suggested. PMID- 26380561 TI - Parathyroidectomy Ameliorates Glucose and Blood Pressure Control in a Patient with Primary Hyperparathyroidism, Type 2 Diabetes, and Hypertension. AB - Effect of parathyroidectomy on glucose control and hypertension is controversial. Here, we report a case of a patient with primary hyperparathyroidism, type 2 diabetes mellitus, and hypertension in whom parathyroidectomy ameliorated both glucose control and blood pressure. Once high serum calcium levels were noticed, ultrasonography of neck confirmed a well-defined oval hypoechoic mass posterior to the right lobe of the thyroid, confirmed by scintiscan. Parathyroidectomy resulted in improvement of blood pressure and blood glucose. We could stop insulin and antihypertensive medications. We conclude that in patients with type 2 diabetes with vague complaints like fatigue, body ache, and refractory hypertension, as a part of the diagnostic workup, clinicians should also check serum calcium levels and parathyroid hormone to rule out hyperparathyroidism. Correction of hyperparathyroidism may result in improvement of hypertension and glucose control. PMID- 26380562 TI - Gemcitabine-Induced Pulmonary Toxicity: A Case Report of Pulmonary Veno-Occlusive Disease. AB - INTRODUCTION: Gemcitabine is a chemotherapeutic agent frequently used by for the treatment of several malignancies both in the adjuvant and metastatic setting. Although myelosuppression is the most adverse event of this therapy, gemcitabine might induce severe pulmonary toxicities. We describe a case of pulmonary veno occlusive disease (PVOD) related to gemcitabine. CASE PRESENTATION: The patient was an 83-year-old man with a metastatic pancreatic cancer who was treated by gemcitabine as first-line therapy. He was in good health and received no other chemotherapy. A dose of 1000 mg/m(2) of gemcitabine was administered over a 30 minute intravenous infusion on days 1, 8, and 15 of a 28-day cycle. After a period of 6 months, a complete response was observed. Nevertheless, the patient developed a severe dyspnea, with arterial hypoxemia and very low lung diffusion for carbon monoxide. A CT scan showed diffuse ground glass opacities with septal lines, bilateral pleural effusion, and lymph node enlargement. On echocardiography, there was a suspicion of pulmonary hypertension with elevated systolic pulmonary artery pressure and normal left ventricular pressures. Right heart catheterization confirmed pulmonary hypertension and normal pulmonary artery occlusion pressure. Diagnosis of PVOD was made, and a gemcitabine-induced toxicity was suspected. A symptomatic treatment was started. At last follow-up, patient was in functional class I with near-normal of CT scan, arterial blood gases, and echocardiography. A gemcitabine-induced PVOD is the more likely diagnosis. PMID- 26380563 TI - Law enforcement officers' risk perceptions toward on-duty motor-vehicle events. AB - PURPOSE: Motor-vehicle-related events (MVEs) are the leading cause of on-duty death for law enforcement officers, yet little is known about how officers view this significant job hazard. The purpose of this paper is to explore officers' motor-vehicle risk perception and examine how prior on-duty MVEs and the death or injury of a fellow officer influences this perception. DESIGN/METHODOLOGY/APPROACH: A state-wide random sample of 136 law enforcement agencies was drawn using publically accessible databases, stratified on type and size of agency. In total, 60 agencies agreed to participate and a cross-sectional questionnaire was distributed to 1,466 officers. Using six-point Likert scales, composite scores for motor-vehicle and intentional violence risk perception were derived. A linear regression multivariable model was used to examine factors affecting motor-vehicle risk perception. FINDINGS: Motor-vehicle risk perception scores were significantly higher than intentional violence scores. A prior on duty motor-vehicle crash, prior roadside incident, or knowledge of fellow officer's injury or death from a MVE significantly increased motor-vehicle risk perception scores. After controlling for potential confounders though, only prior on-duty crashes and roadside incidents impacted motor-vehicle risk perception. RESEARCH LIMITATIONS/IMPLICATIONS: The study comprised primarily small, rural agencies and generalizability may be limited. Also, although the data were collected anonymously, reporting and response biases may affect these findings. ORIGINALITY/VALUE: This study involved a large and diverse cohort of officers and explored motor-vehicle risk perception. A better understanding of officers' risk perceptions will assist in the development and implementation of occupational injury prevention programs, training, and policy. PMID- 26380564 TI - A comparison of alternative strategies for choosing control populations in observational studies. AB - Various approaches have been used to select control groups in observational studies: (1) from within the intervention area; (2) from a convenience sample, or randomly chosen areas; (3) from areas matched on area-level characteristics; and (4) nationally. The consequences of the decision are rarely assessed but, as we show, it can have complex impacts on confounding at both the area and individual levels. We began by reanalyzing data collected for an evaluation of a rapid response service on rates of unplanned hospital admission. Balance on observed individual-level variables was better with external than local controls, after matching. Further, when important prognostic variables were omitted from the matching algorithm, imbalances on those variables were also minimized using external controls. Treatment effects varied markedly depending on the choice of control area, but in the case study the variation was minimal after adjusting for the characteristics of areas. We used simulations to assess relative bias and means-squared error, as this could not be done in the case study. A particular feature of the simulations was unexplained variation in the outcome between areas. We found that the likely impact of unexplained variation for hospital admissions dwarfed the benefits of better balance on individual-level variables, leading us to prefer local controls in this instance. In other scenarios, in which there was less unexplained variation in the outcome between areas, bias and mean-squared error were optimized using external controls. We identify some general considerations relevant to the choice of control population in observational studies. PMID- 26380566 TI - The [Formula: see text] transition form factor from space- and time-like experimental data. AB - The [Formula: see text] transition form factor is analyzed for the first time in both space- and time-like regions at low and intermediate energies in a model independent approach through the use of rational approximants. The [Formula: see text] experimental data provided by the A2 Collaboration in the very low-energy region of the dielectron invariant mass distribution allows for the extraction of the most precise up-to-date slope and curvature parameters of the form factors as well as their values at zero and infinity. The impact of these new results on the mixing parameters of the [Formula: see text]-[Formula: see text] system, together with the role played by renormalization dependent effects, and on the determination of the [Formula: see text] couplings from [Formula: see text] and [Formula: see text] radiative decays is also discussed. PMID- 26380569 TI - Impact of Clinical Pharmacist on the Pediatric Intensive Care Practice: An 11 Year Tertiary Center Experience. AB - OBJECTIVES: With increasing complexity of critical care medicine comes an increasing need for multidisciplinary involvement in care. In many institutions, pharmacists are an integral part of this team, but long-term data on the interventions performed by pharmacists and their effects on patient care and outcomes are limited. We aimed to describe the role of pediatric clinical pharmacists in pediatric intensive care unit (PICU) practice. METHODS: We retrospectively reviewed the records of pharmacy interventions in the PICU at the Mayo Clinic in Rochester, Minnesota, from 2003-2013, with a distinct period of increased pharmacist presence in the PICU from 2008 onward. We compared demographic and outcome data on patients who did and who did not have pharmacy interventions during 2 periods (2003-2007 and 2008-2013). RESULTS: We identified 27,773 total interventions by pharmacists during the 11-year period, of which 79.8% were accepted by the clinical team. These interventions were made on 10,963 unique PICU admissions and prevented 5867 order entry errors. Pharmacists' interventions increased year over year, including a significant change in 2008. Patients who required pharmacy involvement were younger, sicker, and had longer intensive care unit, hospital, and ventilator duration. Average central line infections and central line entry rates decreased significantly over the study period. CONCLUSIONS: Increased pharmacist presence in the PICU is associated with increased interventions and prevention of adverse drug events. Pharmacist participation during rounds and order entry substantially improved the care of critically sick children and should be encouraged. PMID- 26380570 TI - Current Opinions on Stress-Related Mucosal Disease Prevention in Canadian Pediatric Intensive Care Units. AB - OBJECTIVE: To describe current opinions about stress-related mucosal disease (SRMD) prevention in Canadian pediatric intensive care units (PICUs). METHODS: A 22-question survey covering several aspects of SRMD was sent to all identified PICU attendings in Canada. RESULTS: Sixty-eight percent of identified attendings completed the questionnaire. Thirty-eight percent were based in Quebec, 31% in Alberta, and 31% from other provinces. Most attendings (78%) had worked in a PICU for 6 years or more. When asked about risk factors for prescribing SRMD prevention drugs (more than 1 answer was accepted), the most popular answers were prior history of gastric ulceration/bleeding (33 respondents), coagulopathy (28 respondents), and major neurologic insult (18 respondents). Almost half of the attendings (48%) mentioned that they prescribe SRMD prophylaxis directly upon PICU admission to more than 25% of their patients. Forty-nine percent of respondents subjectively estimated that clinically significant upper gastrointestinal bleeding (UGIB; defined as UGIB associated with either hypotension, transfusion within 24 hours of the event, or death) occurred in less than 1% of their patients. Fifty-seven respondents (93%) used ranitidine as first line therapy (average dose: 4.1 mg/kg/day, mainly intravenously). As second-line therapy, 32 attendings (52%) used pantoprazole and 13 (21%) used omeprazole. CONCLUSIONS: Despite the paucity of guidelines on SRMD prevention and the low reported incidence of clinically significant UGIB, SRMD prevention is frequently used in Canadian PICUs. Ranitidine is the first-line drug used by most attendings. PMID- 26380571 TI - Dosing of Appropriate Antibiotics and Time to Administration of First Doses in the Pediatric Emergency Department. AB - OBJECTIVES: Emergency department (ED) providers are faced with the challenge of diagnosing and treating patients in a timely fashion given many obstacles including limited patient information, complex disease states, and high patient turnover. Time delays in administration or selection of appropriate drug therapies have been associated with negative outcomes in severe infections. This study was conducted to assess the impact of an emergency medicine pharmacist (EPh) on the selection of appropriate antibiotics and the timeliness of administration in pediatric patients in the ED. METHODS: Patients younger than 18 years were evaluated who were admitted through the ED and received 1 dose of intravenous antibiotic for the following conditions: community-acquired pneumonia, complicated skin and soft tissue infection (SSTI), meningitis, and sepsis. To evaluate the impact of the presence of an EPh, patients with orders placed during the EPh's hours of 1 pm and 11 pm were compared to those with an order placed between 11 pm and 1 pm. RESULTS: A total of 142 patients were included in the study. Patients seen during EPh hours received an appropriate first antibiotic 93.4% of the time (p = 0.157) and second antibiotic 96.8% of the time (p = 0.023). Time from order to verification was significantly shorter for the first 2 antimicrobials in the EPh group (10.5 minutes [p = 0.003] and 11.4 minutes [p = 0.047], respectively). The days from discharge to return to readmission to the ED were also significantly different (17.5 days vs. 62.4 days, p = 0.008). CONCLUSIONS: The available data suggest that patients are more likely to receive appropriate doses of antimicrobials, and in a more timely fashion, whenever the EPh is present. Areas for future investigation include whether the presence of EPhs at the bedside has the potential to impact areas of patient care, including readmission rates, drug costs, and medication errors. PMID- 26380572 TI - Unlicensed and Off-Label Drug Use in Children Before and After Pediatric Governmental Initiatives. AB - OBJECTIVES: Governmental agencies (US Food and Drug Administration and European Medicines Agency) implemented initiatives to improve pediatric clinical research, starting in 1997 and 2007, respectively. The aim of this review was to quantify the unlicensed and off-label drug uses in children before and after these implementations. METHODS: Literature review of unlicensed and off-label drug uses was performed on PubMed and Google-Scholar from 1985 to 2014. Relevant titles/abstracts were reviewed, and articles were included if evaluating unlicensed/off-label drug uses, with a clear description of health care setting and studied population. Included articles were divided into 3 groups: studies conducted in United States (before/after 2007), in Europe (before/after 2007), and in other countries. RESULTS: Of the 48 articles reviewed, 27 were included. Before implementation of pediatric initiatives, global unlicensed drug use rate in Europe was found to be 0.2% to 36% for inpatients and 0.3% to 16.6% for outpatients. After implementation, it marginally decreased to 11.4% and 1.26% to 6.7%, respectively. Concerning off-label drug use rates, it was found to be 18% to 66% for inpatients and 10.5% to 37.5% for outpatients before the implementation. After implementation, it decreased marginally to 33.2% to 46.5% and to 3.3% to 13.5%, respectively. In other countries, unlicensed and off-label drug use rates were found to be, respectively, 8% to 27.3% and 11% to 47%. CONCLUSIONS: Governmental initiatives to improve clinical research conducted in children seem to have had a marginal effect to decrease the unlicensed and off label drug uses prevalence in Europe. PMID- 26380567 TI - 2-Hydroxy Acids in Plant Metabolism. AB - Glycolate, malate, lactate, and 2-hydroxyglutarate are important 2-hydroxy acids (2HA) in plant metabolism. Most of them can be found as D- and L-stereoisomers. These 2HA play an integral role in plant primary metabolism, where they are involved in fundamental pathways such as photorespiration, tricarboxylic acid cycle, glyoxylate cycle, methylglyoxal pathway, and lysine catabolism. Recent molecular studies in Arabidopsis thaliana have helped elucidate the participation of these 2HA in in plant metabolism and physiology. In this chapter, we summarize the current knowledge about the metabolic pathways and cellular processes in which they are involved, focusing on the proteins that participate in their metabolism and cellular/intracellular transport in Arabidopsis. PMID- 26380568 TI - Treatment of Generalized Convulsive Status Epilepticus in Pediatric Patients. AB - Generalized convulsive status epilepticus (GCSE) is one of the most common neurologic emergencies and can be associated with significant morbidity and mortality if not treated promptly and aggressively. Management of GCSE is staged and generally involves the use of life support measures, identification and management of underlying causes, and rapid initiation of anticonvulsants. The purpose of this article is to review and evaluate published reports regarding the treatment of impending, established, refractory, and super-refractory GCSE in pediatric patients. PMID- 26380573 TI - Dexmedetomidine Infusion to Control Agitation due to Anticholinergic Toxidromes in Adolescents, a Case Series. AB - Dexmedetomidine is an alpha2-adrenergic agonist approved by the US Food and Drug Administration for the sedation of adults who are intubated on mechanical ventilation and in non-intubated adults who are undergoing surgical procedures. However, it has also recently become a commonly used sedative agent in varied clinical settings for the pediatric patient as well. We present the use of dexmedetomidine for sedation in a unique clinical scenario, the severely agitated and combative patient following the intentional misuse of anticholinergic drugs. Its applications in this situation are discussed, and previous reports in the literature are reviewed. PMID- 26380574 TI - Morphine: An Effective Abortive Therapy for Pediatric Paroxysmal Sympathetic Hyperactivity After Hypoxic Brain Injury. AB - Paroxysmal sympathetic hyperactivity (PSH) is a life-threatening condition characterized by hyperadrenergic activity and autonomic dysfunction. Also termed autonomic storms, PSH can occur after a variety of cerebral insults, most commonly traumatic brain injury. Limited pediatric literature is available, especially in patients with brain injury from hypoxia. No consensus exists for the terminology, diagnostic criteria, or treatment algorithm for PSH. Thus, the optimal management, including medication selection and dosing, remains unclear. We present the detailed treatment of a 9-year-old, African American male with hypoxic brain injury after pulseless arrest following status asthmaticus, who subsequently developed PSH. The patient began to experience episodes of tachycardia, hypertension, tachypnea, diaphoresis, rigidity, and dystonic posturing on hospital day 5. After ruling out other potential causes, a diagnosis of PSH was made. Episodes of PSH failed to respond to lorazepam or labetalol but were aborted successfully with morphine. Management of PSH after hypoxic brain injury required medications for acute treatment as well as for prevention of PSH. Morphine was found to be highly effective and safe for aborting the autonomic crises. Other agents more commonly described in the literature did not result in an adequate response and were associated with significant adverse effects. A combination of clonazepam, baclofen, and either propranolol or clonidine aided in reducing the frequency of episodes of PSH. We suggest using morphine for aborting severe episodes of PSH that do not respond to antihypertensive agents or benzodiazepines. PMID- 26380575 TI - Concentric Tube Robot Design and Optimization Based on Task and Anatomical Constraints. AB - Concentric tube robots are catheter-sized continuum robots that are well suited for minimally invasive surgery inside confined body cavities. These robots are constructed from sets of pre-curved superelastic tubes and are capable of assuming complex 3D curves. The family of 3D curves that the robot can assume depends on the number, curvatures, lengths and stiffnesses of the tubes in its tube set. The robot design problem involves solving for a tube set that will produce the family of curves necessary to perform a surgical procedure. At a minimum, these curves must enable the robot to smoothly extend into the body and to manipulate tools over the desired surgical workspace while respecting anatomical constraints. This paper introduces an optimization framework that utilizes procedureor patient-specific image-based anatomical models along with surgical workspace requirements to generate robot tube set designs. The algorithm searches for designs that minimize robot length and curvature and for which all paths required for the procedure consist of stable robot configurations. Two mechanics-based kinematic models are used. Initial designs are sought using a model assuming torsional rigidity. These designs are then refined using a torsionally-compliant model. The approach is illustrated with clinically relevant examples from neurosurgery and intracardiac surgery. PMID- 26380576 TI - Optical Response of Silver Nanoneedles on a Mirror. AB - Plasmonic properties of metal nanostructures are appealing due to their potential to enhance photovoltaics or sensing performance. Our aim was to identify the plasmonic characteristics of silver nanoneedles on a reflective layer in the polarized optical response. Experimental ellipsometry results are complemented by finite-difference time-domain (FDTD) calculations. Plasmon resonances on the nanoneedles can indeed be observed in the polarized optical response. This study reveals the details of the complex antenna-like behaviour of the nanoneedles which gives an agreement between experiment and FDTD simulation. The simulations show that the plasmon resonances lead to an effective negative refractive index, originating from the negative refractive index of the nanoneedles in combination with its supporting substrate, i.e. a mirror. This original study of a complex plasmonic system by ellipsometry and FDTD has great relevance for applications, making use of intricate light matter interaction. PMID- 26380577 TI - Sibling popularity: A moderator of sibling influence for adolescent substance use. AB - Sibling substance use is a known correlate of adolescent substance use. Yet, not all siblings are equally influential. Sibling influence has been found to vary by age gap, sex, and birth order. Little research, however, has investigated whether siblings' peer context is also a source of variation. The present study tested whether more popular siblings were more influential for adolescent use of cigarettes, alcohol, and marijuana. Data were obtained from sibling pairs in the National Longitudinal Study of Adolescent Health. Findings indicate that older siblings have more influence on younger sibling marijuana use when they have more friends. These findings contribute to prior work examining which siblings are more influential and highlight the need to consider siblings as part of a greater peer context. PMID- 26380579 TI - Contamination of health care workers' coats at the University Teaching Hospital in Lusaka, Zambia: the nosocomial risk. AB - BACKGROUND: Health care Associated Infections (HAIs) are a major public health problem in both developed and developing countries. They pose a severe impact in resource-poor settings, where the rate of infection is estimated to be relatively high. Therefore, this study was conducted to establish empirical evidence related to HAIs in Zambia. METHOD: This was a prospective cross-sectional study conducted from October, 2013 to May 2014 at the University Teaching Hospital (UTH) in Lusaka. A total of 107 white coats worn by health care-workers at UTH were sampled for possible bacteriological contamination. RESULTS: Of the 107 white coats screened, 94 (72.8 %) were contaminated with bacteria. There was no difference in the contamination levels between white coats worn for more than 60 min (47.8 %) compared to those worn for 30-60 min (46.7 %) (p = 0.612). Further, the antibiotic sensitivity tests indicated that the bacterial isolates were resistant to some of the antibiotics assessed. Isolates of Staphylococcus aureus and Klebsiella pnumoniae exhibited the highest resistance to most of the antibiotics assessed. CONCLUSION: This study has shown that white coats worn by health care-workers at the University Teaching Hospital generally have high microbial contaminations and hence pose a nosocomial risk. It is therefore, recommended that white coats be regularly sanitized, and health care workers also be sensitized on public health risk of HAIs associated with contaminated coats. PMID- 26380578 TI - Hormetic effect of rotenone in primary human fibroblasts. AB - BACKGROUND: Rotenone inhibits the electron transfer from complex I to ubiquinone, in this way interfering with the electron transport chain in mitochondria. This chain of events induces increased levels of intracellular reactive oxygen species, which in turn can contribute to acceleration of telomere shortening and induction of DNA damage, ultimately resulting in aging. In this study, we investigated the effect of rotenone treatment in human fibroblast strains. RESULTS: For the first time we here describe that rotenone treatment induced a hormetic effect in human fibroblast strains. We identified a number of genes which were commonly differentially regulated due to low dose rotenone treatment in fibroblasts independent of their cell origin. However, these genes were not among the most strongly differentially regulated genes in the fibroblast strains on treatment with rotenone. Thus, if there is a common hormesis regulation, it is superimposed by cell strain specific individual responses. We found the rotenone induced differential regulation of pathways common between the two fibroblast strains, being weaker than the pathways individually regulated in the single fibroblast cell strains. Furthermore, within the common pathways different genes were responsible for this different regulation. Thus, rotenone induced hormesis was related to a weak pathway signal, superimposed by a stronger individual cellular response, a situation as found for the differentially expressed genes. CONCLUSION: We found that the concept of hormesis also applies to in vitro aging of primary human fibroblasts. However, in depth analysis of the genes as well as the pathways differentially regulated due to rotenone treatment revealed cellular hormesis being related to weak signals which are superimposed by stronger individual cell-internal responses. This would explain that in general hormesis is a small effect. Our data indicate that the observed hormetic phenotype does not result from a specific strong well-defined gene or pathway regulation but from weak common cellular processes induced by low levels of reactive oxygen species. This conclusion also holds when comparing our results with those obtained for C. elegans in which the same low dose rotenone level induced a life span extending, thus hormetic effect. PMID- 26380580 TI - Coincident polio and Ebola crises expose similar fault lines in the current global health regime. AB - BACKGROUND: In 2014, the World Health Organization (WHO) declared two "public health emergencies of international concern", in response to the worldwide polio situation and the Ebola epidemic in West Africa respectively. Both emergencies can be seen as testing moments, challenging the current model of epidemic governance, where two worldviews co-exist: global health security and humanitarian biomedicine. DISCUSSION: The resurgence of polio and the spread of Ebola in 2014 have not only exposed the weaknesses of national health systems, but also the shortcomings of the current global health regime in dealing with transnational epidemic threats. These shortcomings are of three sorts. Firstly, the global health regime is fragmented and dominated by the domestic security priorities of industrialised nations. Secondly, the WHO has been constrained by constitutional country allegiances, crippling reforms and the limited impact of the (2005) International Health Regulations (IHR) framework. Thirdly, the securitization of infectious diseases and the militarization of humanitarian aid undermine the establishment of credible public health surveillance networks and the capacity to control epidemic threats. SUMMARY: The securitization of communicable diseases has so far led foreign aid policies to sideline health systems. It has also been the source of ongoing misperceptions over the aims of global health initiatives. With its strict allegiance to Member States, the WHO mandate is problematic, particularly when it comes to controlling epidemic diseases. In this context, humanitarian medical organizations are expected to palliate the absence of public health services in the most destitute areas, particularly in conflict zones. The militarization of humanitarian aid itself threatens this fragile and imperfect equilibrium. None of the reforms announced by the WHO in the wake of the 68(th) World Health Assembly address these fundamental issues. PMID- 26380581 TI - Butanol production from food waste: a novel process for producing sustainable energy and reducing environmental pollution. AB - BACKGROUND: Waste is currently a major problem in the world, both in the developing and the developed countries. Efficient utilization of food waste for fuel and chemical production can positively influence both the energy and environmental sustainability. This study investigated using food waste to produce acetone, butanol, and ethanol (ABE) by Clostridium beijerinckii P260. RESULTS: In control fermentation, 40.5 g/L of glucose (initial glucose 56.7 g/L) was used to produce 14.2 g/L of ABE with a fermentation productivity and a yield of 0.22 g/L/h and 0.35 g/g, respectively. In a similar fermentation 81 g/L of food waste (containing equivalent glucose of 60.1 g/L) was used as substrate, and the culture produced 18.9 g/L ABE with a high ABE productivity of 0.46 g/L/h and a yield of 0.38 g/g. Fermentation of food waste at higher concentrations (129, 181 and 228 g/L) did not remarkably increase ABE production but resulted in high residual glucose due to the culture butanol inhibition. An integrated vacuum stripping system was designed and applied to recover butanol from the fermentation broth simultaneously to relieve the culture butanol inhibition, thereby allowing the fermentation of food waste at high concentrations. ABE fermentation integrated with vacuum stripping successfully recovered the ABE from the fermentation broth and controlled the ABE concentrations below 10 g/L during fermentation when 129 g/L food waste was used. The ABE productivity with vacuum fermentation was 0.49 g/L/h, which was 109 % higher than the control fermentation (glucose based). More importantly, ABE vacuum recovery and fermentation allowed near-complete utilization of the sugars (~98 %) in the broth. CONCLUSIONS: In these studies it was demonstrated that food waste is a superior feedstock for producing butanol using Clostridium beijerinckii. Compared to costly glucose, ABE fermentation of food waste has several advantages including lower feedstock cost, higher productivity, and less residual sugars. PMID- 26380583 TI - Autonomous Driver Based on an Intelligent System of Decision-Making. AB - The paper presents and discusses a system (xDriver) which uses an Intelligent System of Decision-making (ISD) for the task of car driving. The principal subject is the implementation, simulation and testing of the ISD system described earlier in our publications (Kowalczuk and Czubenko in artificial intelligence and soft computing lecture notes in computer science, lecture notes in artificial intelligence, Springer, Berlin, 2010, 2010, In Int J Appl Math Comput Sci 21(4):621-635, 2011, In Pomiary Autom Robot 2(17):60-5, 2013) for the task of autonomous driving. The design of the whole ISD system is a result of a thorough modelling of human psychology based on an extensive literature study. Concepts somehow similar to the ISD system can be found in the literature (Muhlestein in Cognit Comput 5(1):99-105, 2012; Wiggins in Cognit Comput 4(3):306-319, 2012), but there are no reports of a system which would model the human psychology for the purpose of autonomously driving a car. The paper describes assumptions for simulation, the set of needs and reactions (characterizing the ISD system), the road model and the vehicle model, as well as presents some results of simulation. It proves that the xDriver system may behave on the road as a very inexperienced driver. PMID- 26380582 TI - Cells adapt to the epigenomic disruption caused by histone deacetylase inhibitors through a coordinated, chromatin-mediated transcriptional response. AB - BACKGROUND: The genome-wide hyperacetylation of chromatin caused by histone deacetylase inhibitors (HDACi) is surprisingly well tolerated by most eukaryotic cells. The homeostatic mechanisms that underlie this tolerance are unknown. Here we identify the transcriptional and epigenomic changes that constitute the earliest response of human lymphoblastoid cells to two HDACi, valproic acid and suberoylanilide hydroxamic acid (Vorinostat), both in widespread clinical use. RESULTS: Dynamic changes in transcript levels over the first 2 h of exposure to HDACi were assayed on High Density microarrays. There was a consistent response to the two different inhibitors at several concentrations. Strikingly, components of all known lysine acetyltransferase (KAT) complexes were down-regulated, as were genes required for growth and maintenance of the lymphoid phenotype. Up regulated gene clusters were enriched in regulators of transcription, development and phenotypic change. In untreated cells, HDACi-responsive genes, whether up- or down-regulated, were packaged in highly acetylated chromatin. This was essentially unaffected by HDACi. In contrast, HDACi induced a strong increase in H3K27me3 at transcription start sites, irrespective of their transcriptional response. Inhibition of the H3K27 methylating enzymes, EZH1/2, altered the transcriptional response to HDACi, confirming the functional significance of H3K27 methylation for specific genes. CONCLUSIONS: We propose that the observed transcriptional changes constitute an inbuilt adaptive response to HDACi that promotes cell survival by minimising protein hyperacetylation, slowing growth and re-balancing patterns of gene expression. The transcriptional response to HDACi is mediated by a precisely timed increase in H3K27me3 at transcription start sites. In contrast, histone acetylation, at least at the three lysine residues tested, seems to play no direct role. Instead, it may provide a stable chromatin environment that allows transcriptional change to be induced by other factors, possibly acetylated non-histone proteins. PMID- 26380584 TI - Decreased efficacy of drugs targeting the vascular endothelial growth factor pathway by the epigenetic silencing of FLT1 in renal cancer cells. AB - BACKGROUND: The vascular endothelial growth factor (VEGF)-VEGF receptor (VEGFR) signaling pathway is involved in cancer-related biological functions and is a therapeutic target in cancer. However, the influence of epigenetic regulation of VEGF-VEGFR signaling-related genes remains unclear. Here, we evaluated the effects of FLT1 and KDR promoter hypermethylation combined with drugs targeting VEGF-VEGFR signaling on cancer-related phenotypes in renal cancer cells (RCCs) and examined changes in FLT1 and KDR promoter hypermethylation in tissues from patients with renal cancer. RESULTS: In vitro experiments were performed to evaluate the effects of beavacizumab (an anti-VEGF antibody), an anti-FLT1 peptide, an anti-KDR antibody, and the VEGFR tyrosine kinase inhibitors (TKIs) sunitinib and axitinib in 13 RCC lines with different levels of FLT1 and/or KDR promoter methylation and in 2 FLT1 or KDR in vitro knockdown models. The synergistic effects of sunitinib and axitinib treatment were also evaluated in four RCC lines having different levels of FLT1 and/or KDR methylation. In our in vitro experiments, bevacizumab and an anti-KDR antibody did not affect the proliferation of RCCs having FLT1 and/or KDR hypermethylation. In contrast, in RCCs with FLT1 hypermethylation, proliferation inhibition was counteracted by treatment with an anti-FLT1 peptide and both VEGF-TKIs (sunitinib and axitinib). Demethylation with sunitinib or axitinib synergistically increased proliferation inhibition in the RCCs exhibiting FLT1 hypermethylation. Using in vitro FLT1 or KDR knockdown models, decreased proliferation inhibition following anti-FLT1 peptide, sunitinib, and axitinib treatment was observed only in FLT1-knockdown cells. In patients with renal cancer who received sunitinib, FLT1 promoter methylation was higher in renal cancer tissues from eight nonresponders (stable or progressive disease assessed by the Response Evaluation Criteria in Solid Tumors) than in cancer tissues from five responders (complete response or partial response). CONCLUSIONS: The present data showed that hypermethylated FLT1 was important for the efficacy of anti-VEGF/VEGFR drugs targeting FLT1 or intracellular VEGFR signaling. FLT1 hypermethylation causing alterations of FLT1 function could serve as a useful biomarker for predicting changes in FLT1 status in RCCs. PMID- 26380585 TI - Whole-genome bisulfite sequencing of cell-free DNA identifies signature associated with metastatic breast cancer. AB - BACKGROUND: A number of clinico-pathological criteria and molecular profiles have been used to stratify patients into high- and low-risk groups. Currently, there are still no effective methods to determine which patients harbor micrometastatic disease after standard breast cancer therapy and who will eventually develop local or distant recurrence. The purpose of our study was to identify circulating DNA methylation changes that can be used for prediction of metastatic breast cancer (MBC). RESULTS: Differential methylation analysis revealed ~5.0 * 10(6) differentially methylated CpG loci in MBC compared with healthy individuals (H) or disease-free survivors (DFS). In contrast, there was a strong degree of similarity between H and DFS. Overall, MBC demonstrated global hypomethylation and focal CpG island (CPGI) hypermethylation. Data analysis identified 21 novel hotspots, within CpG islands, that differed most dramatically in MBC compared with H or DFS. CONCLUSIONS: This unbiased analysis of cell-free (cf) DNA identified 21 DNA hypermethylation hotspots associated with MBC and demonstrated the ability to distinguish tumor-specific changes from normal-derived signals at the whole-genome level. This signature is a potential blood-based biomarker that could be advantageous at the time of surgery and/or after the completion of chemotherapy to indicate patients with micrometastatic disease who are at a high risk of recurrence and who could benefit from additional therapy. PMID- 26380586 TI - Reactions of community members regarding community health workers' activities as a measure of the impact of a training program in Amazonas, Brazil. AB - OBJECTIVES: The aim of this study was to evaluate the impact of community health worker (CHW) training on recognition and satisfaction regarding the performance of CHWs among members of the community in Amazonas, Brazil, which is a resource poor area underserved with regard to medical health-care accessibility. METHODS: Baseline and endline surveys concerning recognition and satisfaction with respect to CHW performance among members of the community were conducted by interview using a questionnaire before and after implementation of a program to strengthen community health projects in Manicore, Amazonas, Brazil. One of the components of the project was CHW refresher training, which focused on facilitating adequate use of health-care services and providing primary health care, including health guidance. The baseline survey was performed in February 2004 at the beginning of the project, and the endline survey was performed in February 2006 at the end of the project. There were 82 and 120 CHWs working in Manicore at the times of the baseline and endline surveys, respectively. Statistical analysis was performed to determine the significance of changes in experience with CHW activities, expected functions of CHWs, and satisfaction regarding the performance of CHWs between the baseline and endline surveys. In addition, qualitative analysis was conducted to evaluate the acceptability, feasibility, and sustainability of CHW refresher training. RESULTS: Overall recognition and level of satisfaction regarding CHW performance among members of the community were improved from the baseline to the endline survey, regardless of type of residential area, such as town and/or remote area. Members of the community came to not expect CHWs to "provide strong medicine" (P < 0.001) and "provide injections" (P < 0.001), and came to appreciate "go to hospital with a sick person" (P = 0.031) as a function and role of CHWs. CONCLUSIONS: The results of the present study indicated that steady approaches to motivate and support CHWs in resource-limited settings could improve performance of CHWs and satisfaction of people in the community regarding the activities of CHWs to sustain their health. PMID- 26380587 TI - The effects of coaching on salivary cortisol stress marker in mothers with young children, a randomized controlled trial. AB - OBJECTIVES: The purpose of this study was to evaluate the effects of a coaching program on saliva cortisol sensitivity in normal healthy mothers with young children. METHODS: A randomized controlled trial (RCT) was conducted with objective and subjective outcome measurements of the stress indicator. A postal survey to assess emotional intelligence (EI) was administered by random sampling to mothers of young children aged 3 months to 6 years in Japan. A total of 74 mothers with median EI scores or lower were enrolled in a RCT involving the coaching program. The intervention group received a 3-month coaching program. The control group was given the coaching program at follow-up. Stress state outcomes (saliva cortisol level, EI score, and Profile of Mood States (POMS)) were measured at baseline and immediate follow-up, with salivary cortisol measured again at a one-month follow-up. RESULTS: Significant differences were found for saliva cortisol level and the EI score within and between the intervention and control groups. Some POMS subscale scores were significantly different within the intervention and control groups. CONCLUSION: The participants in the coaching program had significantly reduced saliva cortisol levels and better secondary outcomes than those in the control group. PMID- 26380588 TI - Perspectives concerning living wills in medical staff of a main regional hospital in Japan. AB - OBJECTIVE: Living wills, written types of advanced directives, are now widespread in western countries, but in Japan, their recognition still remains restricted to a small part of the population. As an initial step to introduction of such patient-oriented medicine, we surveyed present recognition and acceptance patterns concerning living wills in a main regional hospital located in a suburban area of Tokyo. METHODS: Without any preceding guidance on living wills, the questionnaire on living wills was distributed to all the staff working at JA Toride Medical Center in September 2013, and their responses were collected for analysis within one month. RESULTS: Questionnaires were distributed to all hospital staff, 843 in total, and 674 responses (80.0% of distributed) were obtained. The term of living will was known by 304 (45.1%) of the respondents, and introduction of living wills to patients was accepted in 373 (55.3%) of the respondents, meanwhile, 286 (42.4%) respondents did not indicate their attitude toward living wills. As to styles of document form, 332 respondents (49.3%) supported selection of wanted or unwanted medical treatments and care from a prepared list, and 102 respondents (15.1%) supported description of living wills in free form. As preferred treatment options that should be provided as a checklist, cardiac massage (chest compression) and a ventilator were selected by more than half of the respondents. Based on their responses, we developed an original type of living wills available to patients visiting the hospital. CONCLUSIONS: Although not all the respondents were aware of living wills even in this main regional hospital, introduction of living wills to patients was accepted by many of the hospital staff. Awareness programs or information campaigns are needed to introduce living wills to support patient-centered medicine. PMID- 26380589 TI - Development of a nursing care problems coping scale for male caregivers for people with dementia living at home. AB - OBJECTIVE: The number of male caregivers has increased, but male caregivers face several problems that reduce their quality of life and psychological condition. This study focused on the coping problems of men who care for people with dementia at home. It aimed to develop a coping scale for male caregivers so that they can continue caring for people with dementia at home and improve their own quality of life. The study also aimed to verify the reliability and validity of the scale. PATIENTS/MATERIAL AND METHODS: The subjects were 759 men who care for people with dementia at home. The Care Problems Coping Scale consists of 21 questions based on elements of questions extracted from a pilot study. Additionally, subjects completed three self-administered questionnaires: the Japanese version of the Zarit Caregiver Burden Scale, the Depressive Symptoms and the Self-esteem Emotional Scale, and Rosenberg Self-Esteem Scale. RESULTS: There were 274 valid responses (36.1% response rate). Regarding the answer distribution, each average value of the 21 items ranged from 1.56 to 2.68. The median answer distribution of the 21 items was 39 (SD = 6.6). Five items had a ceiling effect, and two items had a floor effect. The scale stability was about 50%, and Cronbach's alpha was 0.49. There were significant correlations between the Care Problems Coping Scale and total scores of the Japanese version of the Zarit Caregiver Burden Scale, the Depressive Symptoms and Self-esteem Emotional Scale, and the Rosenberg Self-Esteem Scale. CONCLUSION: The answers provided on the Care Problems Coping Scale questionnaire indicated that male caregivers experience care problems. In terms of validity, there were significant correlations between the external questionnaires and 19 of the 21 items in this scale. This scale can therefore be used to measure problems with coping for male caregivers who care for people with dementia at home. PMID- 26380590 TI - Nontraumatic central fracture dislocation of the hip in a patient with chronic kidney disease and post gastrectomy. AB - OBJECTIVE: PATIENTs with secondary hyperparathyroidism caused by chronic kidney disease (CKD) develop secondary osteoporosis, which increases fracture risk. We report a case of insufficiency fractures complicated by secondary osteoporosis caused by chronic renal failure and gastrectomy. PATIENT: A 78-year-old man with a medical history of nephrotic syndrome and gastric cancer experienced an occult intertrochanteric fracture of his left femur after falling. RESULTS: Ten days after the first fracture, the patient was treated with hemodialysis for acute uremic symptoms. Eight weeks after this fracture, he sustained a right insufficiency acetabular fracture and was treated with total hip arthroplasty (THA). CONCLUSION: For patients with CKD, effective fracture prevention is difficult. THA with reconstruction of the acetabulum was an effective therapy in a patient with nontraumatic central fracture dislocation of the hip. PMID- 26380591 TI - Are eating habits effective screening indicators for anemia in elderly Japanese people? The Kyushu-Asakura Project (KAP). AB - OBJECTIVE: The aim of the present study was to explore whether the presence of unhealthy eating habits is an effective indicator of anemia among older people or not. METHODS: We used data from a prospective observational cohort study of all users who underwent an annual health checkup at a public clinic in a rural area. The subjects of the present study were 150 users aged 75 years and older who underwent the checkup between January and September 2010. The subjects were first divided by gender and further separated into anemic and non-anemic subgroups according to their estimated anemia prevalences: Hb < 130 g/L for males and Hb < 120 g/L for females. For each category, we compared the subjects' lifestyles including eating habits between the anemic and non-anemic groups. RESULTS: Both among the women and the men aged 75 and over, there were no significant differences in any items including eating habits between the two anemic subgroups. CONCLUSION: Our results suggest that the presence of unhealthy eating habits is not an effective indicator of anemia among older people. PMID- 26380593 TI - Oncology Pipeline Full, and Not Just with Immunotherapies. PMID- 26380592 TI - EXPERIENCE OF FORCED SEX AND SUBSEQUENT SEXUAL, DRUG, AND MENTAL HEALTH OUTCOMES: AFRICAN AMERICAN AND HISPANIC WOMEN IN THE SOUTHEASTERN UNITED STATES. AB - OBJECTIVES: This cross-sectional study examined African American and Hispanic women's (N = 1,509) self-reports of unwanted forced sex and its association with behavioral and mental health outcomes after the event. METHODS: Twenty percent of the women had experienced forced sex (1st occurrence at age 15 years or younger for 10%, 1st occurrence at older than 15 years of age for 10%). RESULTS: Regardless of when forced sex 1st occurred, women were more likely to have engaged in unprotected vaginal and anal sex, to have had multiple unprotected sex partners, to have sexually transmitted infections, to have reported binge drinking and illicit drug use, and to exhibit distress and have received mental health counseling. CONCLUSIONS: Forced sex may have wide-ranging behavioral and mental health consequences years later. PMID- 26380594 TI - Value-Based Healthcare Delivery: The Agenda for Oncology. PMID- 26380595 TI - Nivolumab Beats Docetaxel as Second-Line Therapy for Patients with NSCLC. PMID- 26380596 TI - Searching for the Tipping Point in Drug Pricing. PMID- 26380597 TI - FDA Update. PMID- 26380598 TI - Aetna Examines Impact of Site of Service on Chemotherapy Cost. PMID- 26380600 TI - Researchers Dissect the Cost of Targeted Agents. PMID- 26380599 TI - Treating with Checkpoint Inhibitors-Figure $1 Million per Patient. PMID- 26380601 TI - Bevacizumab Wins Cost-Effectiveness Contest in First-Line Metastatic Colorectal Cancer. PMID- 26380603 TI - UnitedHealthcare's Episode-Based Payment Model Program Cuts Cost. PMID- 26380602 TI - Will Necitumumab Be Cost-Effective? PMID- 26380605 TI - Care Pathway for NSCLC Cuts Chemotherapy Cost. PMID- 26380604 TI - Oral Nicotinamide Prevents Common Skin Cancers in High-Risk Patients, Reduces Costs. PMID- 26380606 TI - CAR-T Cells: The Transplants of the Future. PMID- 26380608 TI - Elotuzumab, First-in-Class Monoclonal Antibody Immunotherapy, Improves Outcomes in Patients with Multiple Myeloma. PMID- 26380607 TI - Encouraging Results for Pembrolizumab in Head and Neck Cancer. PMID- 26380609 TI - Lenvatinib Extends Survival in Metastatic Renal-Cell Carcinoma. PMID- 26380610 TI - Study Shows Promise of Precision Medicine for Most Common Type of Lymphoma. PMID- 26380611 TI - Nivolumab Makes Headwinds into Liver Cancer. PMID- 26380612 TI - Value Propositions in Oncology: The Physician Perspective. PMID- 26380613 TI - Anthem's Clinical Pathways Demonstrate Value: The Payer Perspective. PMID- 26380614 TI - ASCO's Value Initiative: A New Framework Seeking to Standardize Patient-Physician Interactions. PMID- 26380616 TI - ASP plus 6% Will Fall by the Wayside, but What Are the Alternatives? PMID- 26380615 TI - Communication Gap with Oncologists, Not Cost, Tops Patients' Value Priorities. PMID- 26380617 TI - Monthly Care Management Payments Called "Win-Win-Win" Reform. PMID- 26380618 TI - Bundling Payments: UnitedHealthcare Dips a Toe in the Water. PMID- 26380619 TI - Enhanced Reimbursement for Oncology Services Pays for Patient-Centered Care. PMID- 26380620 TI - The Push Toward Value-Based Payment for Oncology. PMID- 26380622 TI - ASCO and NCI Launch Largest Precision Medicine Trials Using Real-World Evidence. PMID- 26380621 TI - Palbociclib Prolongs Progression-Free Survival in Patients with Advanced Breast Cancer. PMID- 26380624 TI - Urine Biopsies Detect Early Mutations in Patients with Advanced Cancers. PMID- 26380623 TI - Genetic Abnormality Pinpointed for Intensive Therapy in Wilms Tumor. PMID- 26380625 TI - Adding Ibrutinib to Standard Therapy Reduces Disease Progression by 80% in Previously Treated Patients with CLL. PMID- 26380627 TI - Immunotherapies Steal the Show at ASCO 2015. PMID- 26380626 TI - Adherence to Ibrutinib Therapy Improves Outcomes in Patients with CLL. PMID- 26380628 TI - Combination Immunotherapy Superior to Monotherapy in Patients with Melanoma. PMID- 26380629 TI - Arming Providers and Payers with Treatment- and Value-Based Management Tools for Battling Cancer. PMID- 26380630 TI - Complete genome sequence of Roseophage vB_DshP-R1, which infects Dinoroseobacter shibae DFL12. AB - The Roseophages, a group of marine viruses that uniquely infect the Roseobacter clade of bacteria, play a significant role in marine ecosystems. Here we present a complete genomic sequence of an N4 phage 'vB_DshP-R1', which infects Dinoroseobacter shibae DFL12, together with its structural and genomic features. vB_DshP-R1 has an ~ 75 nm diameter icosahedral structure and a complete genome of 75,028 bp. This is the first genome sequence of a lytic phage of the genus Dinoroseobacter. PMID- 26380631 TI - Draft-genome sequence of Shewanella algae strain C6G3. AB - Shewanella algae strain C6G3, isolated from the 2 uppermost centimeters of muddy sediment of Arcachon Bay (SW Atlantic French coast, sampled in October 2007) has the capability to use a large panel of terminal electron acceptors under anaerobic condition, such as nitrate, nitrite and metal-oxide, and presents a great metabolic versatility. Here, we present the non-contiguous draft-genome sequence of Shewanella algae C6G3, which consists of a 4,879,425 bp. The chromosome contains 5792 predicted genes. In total, the genome consists of 24 rRNA genes, 86 tRNA genes and 5660 genes assigned as protein-coding genes. PMID- 26380632 TI - High-quality permanent draft genome sequence of Rhizobium sullae strain WSM1592; a Hedysarum coronarium microsymbiont from Sassari, Italy. AB - Rhizobium sullae strain WSM1592 is an aerobic, Gram-negative, non-spore-forming rod that was isolated from an effective nitrogen (N2) fixing root nodule formed on the short-lived perennial legume Hedysarum coronarium (also known as Sulla coronaria or Sulla). WSM1592 was isolated from a nodule recovered from H. coronarium roots located in Ottava, bordering Sassari, Sardinia in 1995. WSM1592 is highly effective at fixing nitrogen with H. coronarium, and is currently the commercial Sulla inoculant strain in Australia. Here we describe the features of R. sullae strain WSM1592, together with genome sequence information and its annotation. The 7,530,820 bp high-quality permanent draft genome is arranged into 118 scaffolds of 118 contigs containing 7.453 protein-coding genes and 73 RNA only encoding genes. This rhizobial genome is sequenced as part of the DOE Joint Genome Institute 2010 Genomic Encyclopedia for Bacteria and Archaea-Root Nodule Bacteria (GEBA-RNB) project. PMID- 26380633 TI - Toward a standard in structural genome annotation for prokaryotes. AB - BACKGROUND: In an effort to identify the best practice for finding genes in prokaryotic genomes and propose it as a standard for automated annotation pipelines, 1,004,576 peptides were collected from various publicly available resources, and were used as a basis to evaluate various gene-calling methods. The peptides came from 45 bacterial replicons with an average GC content from 31 % to 74 %, biased toward higher GC content genomes. Automated, manual, and semi-manual methods were used to tally errors in three widely used gene calling methods, as evidenced by peptides mapped outside the boundaries of called genes. RESULTS: We found that the consensus set of identical genes predicted by the three methods constitutes only about 70 % of the genes predicted by each individual method (with start and stop required to coincide). Peptide data was useful for evaluating some of the differences between gene callers, but not reliable enough to make the results conclusive, due to limitations inherent in any proteogenomic study. CONCLUSIONS: A single, unambiguous, unanimous best practice did not emerge from this analysis, since the available proteomics data were not adequate to provide an objective measurement of differences in the accuracy between these methods. However, as a result of this study, software, reference data, and procedures have been better matched among participants, representing a step toward a much-needed standard. In the absence of sufficient amount of exprimental data to achieve a universal standard, our recommendation is that any of these methods can be used by the community, as long as a single method is employed across all datasets to be compared. PMID- 26380634 TI - High quality draft genome sequence of Flavobacterium rivuli type strain WB 3.3 2(T) (DSM 21788(T)), a valuable source of polysaccharide decomposing enzymes. AB - Flavobacterium rivuli Ali et al. 2009 emend. Dong et al. 2013 is one of about 100 species in the genus Flavobacterium (family Flavobacteriacae, phylum Bacteroidetes) with a validly published name, and has been isolated from the spring of a hard water rivulet in Northern Germany. Including all type strains of the genus Myroides and Flavobacterium into the 16S rRNA gene sequence phylogeny revealed a clustering of members of the genus Myroides as a monophyletic group within the genus Flavobacterium. Furthermore, F. rivuli WB 3.3-2(T) and its next relatives seem more closely related to the genus Myroides than to the type species of the genus Flavobacterium, F. aquatile. The 4,489,248 bp long genome with its 3,391 protein-coding and 65 RNA genes is part of the G enomic E ncyclopedia of B acteria and A rchaea project. The genome of F. rivuli has almost as many genes encoding carbohydrate active enzymes (151 CAZymes) as genes encoding peptidases (177). Peptidases comprised mostly metallo (M) and serine (S) peptidases. Among CAZymes, 30 glycoside hydrolase families, 10 glycosyl transferase families, 7 carbohydrate binding module families and 7 carbohydrate esterase families were identified. Furthermore, we found four polysaccharide utilization loci (PUL) and one large CAZy rich gene cluster that might enable strain WB 3.3-2(T) to decompose plant and algae derived polysaccharides. Based on these results we propose F. rivuli as an interesting candidate for further physiological studies and the role of Bacteroidetes in the decomposition of complex polymers in the environment. PMID- 26380635 TI - Non contiguous-finished genome sequence and description of Bacillus jeddahensis sp. nov. AB - Strain JCE(T) was isolated from the fecal sample of a 24-year-old obese man living in Jeddah, Saudi Arabia. It is an aerobic, Gram-positive, rod-shaped bacterium. This strain exhibits a 16S rRNA nucleotide sequence similarity of 97.5 % with Bacillus niacini, the phylogenetically closest species with standing nomenclature. Moreover, the strain JCE(T) presents many phenotypic differences, when it is compared to other Bacillus species, and shows a low MALDI-TOF Mass Spectrometry score that does not allow any identification. Thus, it is likely that this strain represents a new species. Here we describe the features of this organism, together with the complete genome sequence and annotation. The 4,762,944 bp long genome (1 chromosome but no plasmid) contains 4,654 protein coding and 98 RNAs genes, including 92 tRNA genes. The strain JCE(T) differs from most of the other closely Bacillus species by more than 1 % in G + C content. In addition, digital DNA-DNA hybridization values for the genome of the strain JCE(T) against the closest Bacillus genomes range between 19.5 to 28.1, that confirming again its new species status. On the basis of these polyphasic data made of phenotypic and genomic analyses, we propose the creation of Bacillus jeddahensis sp. nov. that contains the strain JCE(T). PMID- 26380636 TI - High quality draft genome sequence of Bacteroides barnesiae type strain BL2(T) (DSM 18169(T)) from chicken caecum. AB - Bacteroides barnesiae Lan et al. 2006 is a species of the genus Bacteroides, which belongs to the family Bacteroidaceae. Strain BL2(T) is of interest because it was isolated from the gut of a chicken and the growing awareness that the anaerobic microbiota of the caecum is of benefit for the host and may impact poultry farming. The 3,621,509 bp long genome with its 3,059 protein-coding and 97 RNA genes is a part of the Genomic Encyclopedia of Type Strains, Phase I: the one thousand microbial genomes (KMG) project. PMID- 26380637 TI - Genome sequence of the haloarchaeon Haloterrigena jeotgali type strain A29(T) isolated from salt-fermented food. AB - Haloterrigena jeotgali is a halophilic archaeon within the family Natrialbaceae that was isolated from shrimp jeotgal, a traditional Korean salt-fermented food. A29(T) is the type strain of H. jeotgali, and is a Gram-negative staining, non motile, rod-shaped archaeon that grows in 10 %-30 % (w/v) NaCl. We present the annotated H. jeotgali A29(T) genome sequence along with a summary of its features. The 4,131,621 bp genome with a GC content of 64.9 % comprises 4,215 protein-coding genes and 127 RNA genes. The sequence can provide useful information on genetic mechanisms that enable haloarchaea to endure a hypersaline environment. PMID- 26380638 TI - High quality draft genome sequence of Corynebacterium ulceribovis type strain IMMIB-L1395(T) (DSM 45146(T)). AB - Corynebacterium ulceribovis strain IMMIB L-1395(T) (= DSM 45146(T)) is an aerobic to facultative anaerobic, Gram-positive, non-spore-forming, non-motile rod-shaped bacterium that was isolated from the skin of the udder of a cow, in Schleswig Holstein, Germany. The cell wall of C. ulceribovis contains corynemycolic acids. The cellular fatty acids are those described for the genus Corynebacterium, but tuberculostearic acid is not present. Here we describe the features of C. ulceribovis strain IMMIB L-1395(T), together with genome sequence information and its annotation. The 2,300,451 bp long genome containing 2,104 protein-coding genes and 54 RNA-encoding genes and is part of the Genomic Encyclopedia of Type Strains, Phase I: the one thousand microbial genomes (KMG) project. PMID- 26380640 TI - High-quality permanent draft genome sequence of the extremely osmotolerant diphenol degrading bacterium Halotalea alkalilenta AW-7(T), and emended description of the genus Halotalea. AB - Members of the genus Halotalea (family Halomonadaceae) are of high significance since they can tolerate the greatest glucose and maltose concentrations ever reported for known bacteria and are involved in the degradation of industrial effluents. Here, the characteristics and the permanent-draft genome sequence and annotation of Halotalea alkalilenta AW-7(T) are described. The microorganism was sequenced as a part of the Genomic Encyclopedia of Type Strains, Phase I: the one thousand microbial genomes (KMG) project at the DOE Joint Genome Institute, and it is the only strain within the genus Halotalea having its genome sequenced. The genome is 4,467,826 bp long and consists of 40 scaffolds with 64.62 % average GC content. A total of 4,104 genes were predicted, comprising of 4,028 protein coding and 76 RNA genes. Most protein-coding genes (87.79 %) were assigned to a putative function. Halotalea alkalilenta AW-7(T) encodes the catechol and protocatechuate degradation to beta-ketoadipate via the beta-ketoadipate and protocatechuate ortho-cleavage degradation pathway, and it possesses the genetic ability to detoxify fluoroacetate, cyanate and acrylonitrile. An emended description of the genus Halotalea Ntougias et al. 2007 is also provided in order to describe the delayed fermentation ability of the type strain. PMID- 26380639 TI - Genome sequence of the pink-pigmented marine bacterium Loktanella hongkongensis type strain (UST950701-009P(T)), a representative of the Roseobacter group. AB - Loktanella hongkongensis UST950701-009P(T) is a Gram-negative, non-motile and rod shaped bacterium isolated from a marine biofilm in the subtropical seawater of Hong Kong. When growing as a monospecies biofilm on polystyrene surfaces, this bacterium is able to induce larval settlement and metamorphosis of a ubiquitous polychaete tubeworm Hydroides elegans. The inductive cues are low-molecular weight compounds bound to the exopolymeric matrix of the bacterial cells. In the present study we describe the features of L. hongkongensis strain DSM 17492(T) together with its genome sequence and annotation and novel aspects of its phenotype. The 3,198,444 bp long genome sequence encodes 3104 protein-coding genes and 57 RNA genes. The two unambiguously identified extrachromosomal replicons contain replication modules of the RepB and the Rhodobacteraceae specific DnaA-like type, respectively. PMID- 26380641 TI - High-Quality draft genome sequence of the Lotus spp. microsymbiont Mesorhizobium loti strain CJ3Sym. AB - Mesorhizobium loti strain CJ3Sym was isolated in 1998 following transfer of the integrative and conjugative element ICEMlSym(R7A), also known as the R7A symbiosis island, in a laboratory mating from the donor M. loti strain R7A to a nonsymbiotic recipient Mesorhizobium strain CJ3. Strain CJ3 was originally isolated from a field site in the Rocklands range in New Zealand in 1994. CJ3Sym is an aerobic, Gram-negative, non-spore-forming rod. This report reveals the genome of M. loti strain CJ3Sym currently comprises 70 scaffolds totaling 7,563,725 bp. The high-quality draft genome is arranged in 70 scaffolds of 71 contigs, contains 7,331 protein-coding genes and 70 RNA-only encoding genes, and is part of the GEBA-RNB project proposal. PMID- 26380642 TI - Complete genome sequence of the phenanthrene-degrading soil bacterium Delftia acidovorans Cs1-4. AB - Polycyclic aromatic hydrocarbons (PAH) are ubiquitous environmental pollutants and microbial biodegradation is an important means of remediation of PAH contaminated soil. Delftia acidovorans Cs1-4 (formerly Delftia sp. Cs1-4) was isolated by using phenanthrene as the sole carbon source from PAH contaminated soil in Wisconsin. Its full genome sequence was determined to gain insights into a mechanisms underlying biodegradation of PAH. Three genomic libraries were constructed and sequenced: an Illumina GAii shotgun library (916,416,493 reads), a 454 Titanium standard library (770,171 reads) and one paired-end 454 library (average insert size of 8 kb, 508,092 reads). The initial assembly contained 40 contigs in two scaffolds. The 454 Titanium standard data and the 454 paired end data were assembled together and the consensus sequences were computationally shredded into 2 kb overlapping shreds. Illumina sequencing data was assembled, and the consensus sequence was computationally shredded into 1.5 kb overlapping shreds. Gaps between contigs were closed by editing in Consed, by PCR and by Bubble PCR primer walks. A total of 182 additional reactions were needed to close gaps and to raise the quality of the finished sequence. The final assembly is based on 253.3 Mb of 454 draft data (averaging 38.4 X coverage) and 590.2 Mb of Illumina draft data (averaging 89.4 X coverage). The genome of strain Cs1-4 consists of a single circular chromosome of 6,685,842 bp (66.7 %G+C) containing 6,028 predicted genes; 5,931 of these genes were protein-encoding and 4,425 gene products were assigned to a putative function. Genes encoding phenanthrene degradation were localized to a 232 kb genomic island (termed the phn island), which contained near its 3' end a bacteriophage P4-like integrase, an enzyme often associated with chromosomal integration of mobile genetic elements. Other biodegradation pathways reconstructed from the genome sequence included: benzoate (by the acetyl-CoA pathway), styrene, nicotinic acid (by the maleamate pathway) and the pesticides Dicamba and Fenitrothion. Determination of the complete genome sequence of D. acidovorans Cs1-4 has provided new insights the microbial mechanisms of PAH biodegradation that may shape the process in the environment. PMID- 26380643 TI - Draft genome sequence of marine-derived Streptomyces sp. TP-A0598, a producer of anti-MRSA antibiotic lydicamycins. AB - Streptomyces sp. TP-A0598, isolated from seawater, produces lydicamycin, structurally unique type I polyketide bearing two nitrogen-containing five membered rings, and four congeners TPU-0037-A, -B, -C, and -D. We herein report the 8 Mb draft genome sequence of this strain, together with classification and features of the organism and generation, annotation and analysis of the genome sequence. The genome encodes 7,240 putative ORFs, of which 4,450 ORFs were assigned with COG categories. Also, 66 tRNA genes and one rRNA operon were identified. The genome contains eight gene clusters involved in the production of polyketides and nonribosomal peptides. Among them, a PKS/NRPS gene cluster was assigned to be responsible for lydicamycin biosynthesis and a plausible biosynthetic pathway was proposed on the basis of gene function prediction. This genome sequence data will facilitate to probe the potential of secondary metabolism in marine-derived Streptomyces. PMID- 26380644 TI - High quality draft genomic sequence of Arenimonas donghaensis DSM 18148(T). AB - Arenimonas donghaensis is the type species of genus Arenimonas which belongs to family Xanthomonadaceae within Gammaproteobacteria. In this study, a total of five type strains of Arenimonas were sequenced. The draft genomic information of A. donghaensis DSM 18148(T) is described and compared with other four genomes of Arenimonas. The genome size of A. donghaensis DSM 18148(T) is 2,977,056 bp distributed in 51 contigs, containing 2685 protein-coding genes and 49 RNA genes. PMID- 26380645 TI - Complete genome sequence of Vibrio anguillarum strain NB10, a virulent isolate from the Gulf of Bothnia. AB - Vibrio anguillarum causes a fatal hemorrhagic septicemia in marine fish that leads to great economical losses in aquaculture world-wide. Vibrio anguillarum strain NB10 serotype O1 is a Gram-negative, motile, curved rod-shaped bacterium, isolated from a diseased fish on the Swedish coast of the Gulf of Bothnia, and is slightly halophilic. Strain NB10 is a virulent isolate that readily colonizes fish skin and intestinal tissues. Here, the features of this bacterium are described and the annotation and analysis of its complete genome sequence is presented. The genome is 4,373,835 bp in size, consists of two circular chromosomes and one plasmid, and contains 3,783 protein-coding genes and 129 RNA genes. PMID- 26380646 TI - Improved-high-quality draft genome sequence of Rhodococcus sp. JG-3, a eurypsychrophilic Actinobacteria from Antarctic Dry Valley permafrost. AB - The actinobacterium Rhodococcus sp. JG-3 is an aerobic, eurypsychrophilic, soil bacterium isolated from permafrost in the hyper arid Upper Dry Valleys of Antarctica. It is yellow pigmented, gram positive, moderately halotolerant and capable of growth from 30 degrees C down to at least -5 degrees C. The 5.28 Mb high-quality-draft genome is arranged into 6 scaffolds, containing 9 contigs and 4998 protein coding genes, with 64 % GC content. Increasing the availability of genome sequences from cold-adapted species is crucial to gaining a better understanding of the molecular traits of cold adaptation in microbes. PMID- 26380647 TI - Complete genome sequence of Bacillus thuringiensis strain HD521. AB - Bacillus thuringiensis is the most widely used biological pesticide in the world. It belongs to the Bacillus cereus sensu lato group, which contains six species. Among these six species, B. thuringiensis, B. anthracis, and B. cereus have a low genetic diversity. B. thuringiensis strain HD521 shows maroon colony which is different from most of the B. thuringiensis strains. Strain HD521 also displays an ability to inhibit plant sheath blight disease pathogen (Rhizoctonia solani AG1 IB) growth and can form bipyramidal parasporal crystals consisting of three cry7 genes. These crystals have an insecticidal activity against Henosepilachna vigintioctomaculata larva (Coleoptera). Here we report the complete genome sequence of strain HD521, which has one chromosome and six circular plasmids. PMID- 26380648 TI - Role of liver resection in the management of multinodular hepatocellular carcinoma. AB - Hepatocellular carcinoma (HCC) is the third leading cause of cancer related deaths worldwide. Various treatment modalities have been applied to HCC depending on the tumor load, functional capacity of the liver and the general condition of the patient. According to Barcelona Clinic Liver Cancer staging strategy and The American Association for the Study of Liver Disease guidelines, surgical resection is not advocated in the tretment of multinodular HCC. Despite this, many recent clinical studies show that, resection can achieve good results in patients with multinodular HCC and 5-year survival rate around 40% can be reached. If resection or transplantation is not performed, these patients are usually managed with palliative procedures such as transarterial chemoembolization, radioembolization and cytotoxic chemotherapy and 5-year survival of this group of patients will be extremely low. Although survival rates are lower and complications may be increased in this group of patients, liver resection can safely be performed in selected patients in experienced centers for the management of multinodular HCC. PMID- 26380649 TI - Compartmentalization of hepatitis B virus: Looking beyond the liver. AB - Hepatitis B virus (HBV) is classically considered to be hepatotropic, but accumulating evidences strongly support its extra-hepatotropic nature too. HBV nucleic acids and proteins have long been reported in a variety of extra-hepatic tissues. Of these, HBV has been studied in details in the peripheral blood mononuclear cells (PBMCs), due to its accessibility. From these studies, it is now well established that PBMCs are permissive to HBV infection, replication, transcription and production of infective virions. Furthermore, molecular evolutionary studies have provided definite evidences towards evolution of HBV genome in PBMCs, which is independent of evolution occurring in the liver, leading to the emergence and selection of compartment specific escape variants or drug resistant strains. These variants/resistant strains of HBV remain restricted within the PBMCs and are rarely detected in the serum/plasma. In addition, HBV infected PBMCs have been reported to be directly transmitted through intrauterine modes, and this infection does not correlate significantly with serum HBV surface antigen or HBV DNA markers. This editorial briefly reviews the current knowledge on this topic, emphasizes and delineates the gaps that are required to be filled to properly understand the biological and clinical relevance of extrahepatic tropism of HBV. PMID- 26380650 TI - Evaluation of antiangiogenic efficacy in advanced hepatocellular carcinoma: Biomarkers and functional imaging. AB - Many years after therapeutic wilderness, sorafenib finally showed a clinical benefit in patients with advanced hepatocellular carcinoma. After the primary general enthusiasm worldwide, some disappointments emerged particularly since no new treatment could exceed or at least match sorafenib in this setting. Without these new drugs, research focused on optimizing care of patients treated with sorafenib. One challenging research approach deals with identifying prognostic and predictive biomarkers of sorafenib in this population. The task still seems difficult; however appropriate investigations could resolve this dilemma, as observed for some malignancies where other drugs were used. PMID- 26380651 TI - Markers of bacterial translocation in end-stage liver disease. AB - Bacterial translocation (BT) refers to the passage of viable bacteria or bacterial products from the intestinal lumen, through the intestinal epithelium, into the systemic circulation and extraintestinal locations. The three principal mechanisms that are thought to be involved in BT include bacterial overgrowth, disruption of the gut mucosal barrier and an impaired host defence. BT is commonly observed in liver cirrhosis and has been shown to play an important role in the pathogenesis of the complications of end stage liver disease, including infections as well as hepatic encephalopathy and hepatorenal syndrome. Due to the importance of BT in the natural history of cirrhosis, there is intense interest for the discovery of biomarkers of BT. To date, several such candidates have been proposed, which include bacterial DNA, soluble CD14, lipopolysaccharides endotoxin, lipopolysaccharide-binding protein, calprotectin and procalcitonin. Studies on the association of these markers with BT have demonstrated not only promising data but, oftentimes, contradictory results. As a consequence, currently, there is no optimal marker that may be used in clinical practice as a surrogate for the presence of BT. PMID- 26380654 TI - Fast track anesthesia for liver transplantation: Review of the current practice. AB - Historically, patients undergoing liver transplantation were left intubated and extubated in the intensive care unit (ICU) after a period of recovery. Proponents of this practice argued that these patients were critically ill and need time to be properly optimized from a physiological and pain standpoint prior to extubation. Recently, there has been a growing movement toward early extubation in transplant centers worldwide. Initially fueled by research into early extubation following cardiac surgery, extubation in the operating room or soon after arrival to the ICU, has been shown to be safe with proper patient selection. Additionally, as experience at determining appropriate candidates has improved, some institutions have developed systems to allow select patients to bypass the ICU entirely and be admitted to the surgical ward after transplant. We discuss the history of early extubation and the arguments in favor and against fast track anesthesia. We also described our practice of fast track anesthesia at Mayo Clinic Florida, in which, we extubate approximately 60% of our patients in the operating room and send them to the surgical ward after a period of time in the post anesthesia recovery unit. PMID- 26380653 TI - Management before hepatectomy for hepatocellular carcinoma with cirrhosis. AB - The global distribution of hepatocellular carcinoma (HCC) varies markedly among regions, and patients in East Asia and Central Africa account for about 80% of all cases. The risk factors are hepatitis B, hepatitis C, alcohol, and etc. The risk of carcinogenesis further increases with progression to hepatic cirrhosis in all liver disorders. Radical treatment of HCC by liver resection without causing liver failure has been established as a safe approach through selection of an appropriate range of resection of the damaged liver. This background indicates that both evaluation of hepatic functional reserve and measures against concomitant diseases such as thrombocytopenia accompanying portal hypertension, prevention of rupture of esophageal varices, reliable control of ascites, and improvement of hypoalbuminemia are important issues in liver resection in patients with hepatic cirrhosis. We review the latest information on perioperative management of liver resection in HCC patients with hepatic cirrhosis. PMID- 26380652 TI - Hepatocellular carcinoma: From clinical practice to evidence-based treatment protocols. AB - Hepatocellular carcinoma (HCC) is one of the major malignant diseases in many healthcare systems. The growing number of new cases diagnosed each year is nearly equal to the number of deaths from this cancer. Worldwide, HCC is a leading cause of cancer-related deaths, as it is the fifth most common cancer and the third most important cause of cancer related death in men. Among various risk factors the two are prevailing: viral hepatitis, namely chronic hepatitis C virus is a well-established risk factor contributing to the rising incidence of HCC. The epidemic of obesity and the metabolic syndrome, not only in the United States but also in Asia, tend to become the leading cause of the long-term rise in the HCC incidence. Today, the diagnosis of HCC is established within the national surveillance programs in developed countries while the diagnosis of symptomatic, advanced stage disease still remains the characteristic of underdeveloped countries. Although many different staging systems have been developed and evaluated the Barcelona-Clinic Liver Cancer staging system has emerged as the most useful to guide HCC treatment. Treatment allocation should be decided by a multidisciplinary board involving hepatologists, pathologists, radiologists, liver surgeons and oncologists guided by personalized -based medicine. This approach is important not only to balance between different oncologic treatments strategies but also due to the complexity of the disease (chronic liver disease and the cancer) and due to the large number of potentially efficient therapies. Careful patient selection and a tailored treatment modality for every patient, either potentially curative (surgical treatment and tumor ablation) or palliative (transarterial therapy, radioembolization and medical treatment, i.e., sorafenib) is mandatory to achieve the best treatment outcome. PMID- 26380655 TI - Progress in the treatment of pulmonary metastases after liver transplantation for hepatocellular carcinoma. AB - Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world, and is the third leading cause of cancer-related death. Liver transplantation (LT) has become a curative treatment for patients with HCC. However, recurrence and metastasis after LT are the main factors reducing long-term survival in patients, and the lung is the most common site of metastasis after LT for HCC, although metastasis to liver, para-aortic lymph nodes and renal periphery are observed. Thus, the treatment of pulmonary metastases after LT for HCC has become a hot research topic, the successful treatment of pulmonary metastases can significantly prolong the survival of LT patients. Although single conventional treatment (chemotherapy, surgery and external beam radiation therapy), immunosuppression, image-guided minimally invasive therapy (radiofrequency ablation, microwave ablation, cryoablation, and brachytherapy) and molecular targeted drugs have had a significant effect, patients do not have durable remission and the long-term survival rate is disappointing. Therefore, improving existing treatments and identifying a more effective combination therapy are important research issues in the prevention and treatment of pulmonary metastases after LT for HCC. The paper reviewed single conventional treatments, new treatments, and combination therapy, to provide a basis for the best treatment of these patients. PMID- 26380656 TI - Differential Expression of MicroRNAs in Papillary Thyroid Carcinoma and Their Role in Racial Disparity. AB - OBJECTIVE: MicroRNAs (miRNAs) are known to play important roles in the diagnosis and prognosis of papillary thyroid cancer (PTC), and they are useful in developing targeted therapies. However, there have been no studies on the existence of racial differences in miRNAs expression that could explain differential overall survival of PTC patients. Expression analysis of miRNAs in major racial groups would be important for optimizing personalized treatment strategies. In the current study, we assessed the differential expression of 8 miRNAs between normal and tumor tissues, and also assessed racial differences between African American (AA) and Caucasian American (CA). METHODS: First, the miRNA expression profiling was performed using formalin-fixed paraffin embedded (FFPE) tissue sections of tumor containing over 70% tumor cells. Normal and tumor sections of thyroid tissues were studied from AA and CA patients. The miRNA microarray profiling was done using miRBase version 18 (LC Sciences, Houston, TX, USA). Quantitative real-time PCR (qRT-PCR) was used to validate expression of 8 selected miRNAs. RESULTS: Ingenuity pathway analysis showed involvement of target genes, such as Ras and NF-kappaB. Deregulated miRNAs such as miR-221 and miR-31 were found to be statistically significant between the two races. Using qRT-PCR, we found that miR-21, miR-146b, miR-221, miR-222, miR-31, and miR-3613 were up regulated while miR-138 and miR-98 were down-regulated in tumors compared to normal tissues. CONCLUSION: Though sample size was small, we found several deregulated miRNAs having racial differences. The differential expression of miRNAs suggest that these miRNAs and their target genes could be useful to gain further mechanistic insight of PTC and their clinical implications, including miRNA replacement therapy or their knockdown strategies. PMID- 26380657 TI - Molecular classification and prediction in gastric cancer. AB - Gastric cancer, a highly heterogeneous disease, is the second leading cause of cancer death and the fourth most common cancer globally, with East Asia accounting for more than half of cases annually. Alongside TNM staging, gastric cancer clinic has two well-recognized classification systems, the Lauren classification that subdivides gastric adenocarcinoma into intestinal and diffuse types and the alternative World Health Organization system that divides gastric cancer into papillary, tubular, mucinous (colloid), and poorly cohesive carcinomas. Both classification systems enable a better understanding of the histogenesis and the biology of gastric cancer yet have a limited clinical utility in guiding patient therapy due to the molecular heterogeneity of gastric cancer. Unprecedented whole-genome-scale data have been catalyzing and advancing the molecular subtyping approach. Here we cataloged and compared those published gene expression profiling signatures in gastric cancer. We summarized recent integrated genomic characterization of gastric cancer based on additional data of somatic mutation, chromosomal instability, EBV virus infection, and DNA methylation. We identified the consensus patterns across these signatures and identified the underlying molecular pathways and biological functions. The identification of molecular subtyping of gastric adenocarcinoma and the development of integrated genomics approaches for clinical applications such as prediction of clinical intervening emerge as an essential phase toward personalized medicine in treating gastric cancer. PMID- 26380659 TI - Local habitat conditions explain the variation in the strength of self-thinning in a stream salmonid. AB - Self-thinning patterns are frequently used to describe density dependence in populations on timescales shorter than the organism's life span and have been used to infer carrying capacity of the environment. Among mobile animals, this concept has been used to document density dependence in stream salmonids, which compete over access to food and space. The carrying capacity, growth conditions, and initial cohort sizes often vary between streams and stream sections, which would influence the onset and strength of the density dependence. Despite much effort in describing habitat relationships in stream fishes, few studies have explicitly tested how the physical environment affects the slope of the thinning curves. Here, we investigate the prevalence and strength of self-thinning in juvenile stages of a steelhead (Oncorhynchus mykiss) population in Idaho, USA. Further, we investigate the roles of local physical habitat and metabolic constraints in explaining the variation in thinning curves among study sites in the watershed. Only yearling steelhead exhibited an overall significant thinning trend, but the slope of the mass-density relationship (-0.53) was shallower than predicted by theory and reported from empirical studies. There was no detectable relationship in subyearling steelhead. Certain abiotic factors explained a relatively large portion of the variation in the strength of the self-thinning among the study reaches. For subyearling steelhead, the slopes were negatively associated with the average water depth and flow velocity in the study sites, whereas slopes in yearlings were steeper in sites that incurred a higher metabolic cost. Our results show that the prevalence and strength of density dependence in natural fish populations can vary across heterogeneous watersheds and can be more pronounced during certain stages of a species' life history, and that environmental factors can mediate the extent to which density dependence is manifested in predictable ways. PMID- 26380660 TI - Validation of daily increment formation in otoliths for Gymnocypris selincuoensis in the Tibetan Plateau, China. AB - Daily increment validation in fish otolith is fundamental to studies on fish otolith microstructure, age determination and life history traits, and thus is critical for species conservation and fishery management. However, it has never been done for Schizothoracine fish, which is the dominant component of fish fauna in the Tibetan Plateau. This study validated the daily increment formation of Gymnocypris selincuoensis, as a representative of Schizothoracine fish, by monitoring the growth of hatchery-reared larvae group and wild-caught post-yolk sac larvae group under controlled experiments. The results from monitoring the hatchery-reared larvae group showed that sagittae and lapilli were found in yolk sac larvae, and formed 5-7 days before hatching, but asterisci were not found until 11 days post-hatching. The first increment in sagittae and lapilli was formed in the first day after hatching. The daily periodicity of increment formation was examined and confirmed in sagittae and lapilli of both larvae groups. However, sagittae were better for age determination than lapilli for larvae at earlier days. For larval G. selincuoensis older than 50 days, lapilli were the only otolith pair suitable for larvae daily age determination. This study validated the daily increment formation in Schizothoracine fish for the first time has primary implications to other fishes from this subfamily. PMID- 26380658 TI - Knotted proteins: A tangled tale of Structural Biology. AB - Knotted proteins have their native structures arranged in the form of an open knot. In the last ten years researchers have been making significant efforts to reveal their folding mechanism and understand which functional advantage(s) knots convey to their carriers. Molecular simulations have been playing a fundamental role in this endeavor, and early computational predictions about the knotting mechanism have just been confirmed in wet lab experiments. Here we review a collection of simulation results that allow outlining the current status of the field of knotted proteins, and discuss directions for future research. PMID- 26380661 TI - Ten years of life in compost: temporal and spatial variation of North German Caenorhabditis elegans populations. AB - The nematode Caenorhabditis elegans is a central laboratory model system in almost all biological disciplines, yet its natural life history and population biology are largely unexplored. Such information is essential for in-depth understanding of the nematode's biology because its natural ecology provides the context, in which its traits and the underlying molecular mechanisms evolved. We characterized natural phenotypic and genetic variation among North German C. elegans isolates. We used the unique opportunity to compare samples collected 10 years apart from the same compost heap and additionally included recent samples for this and a second site, collected across a 1.5-year period. Our analysis revealed significant population genetic differentiation between locations, across the 10-year time period, but for only one location a trend across the shorter time frame. Significant variation was similarly found for phenotypic traits of likely importance in nature, such as choice behavior and population growth in the presence of pathogens or naturally associated bacteria. Phenotypic variation was significantly influenced by C. elegans genotype, time of isolation, and sampling site. The here studied C. elegans isolates may provide a valuable, genetically variable resource for future dissection of naturally relevant gene functions. PMID- 26380662 TI - Lineage sorting in multihost parasites: Eidmanniella albescens and Fregatiella aurifasciata on seabirds from the Galapagos Islands. AB - Parasites comprise a significant percentage of the biodiversity of the planet and are useful systems to test evolutionary and ecological hypotheses. In this study, we analyze the effect of host species identity and the immediate local species assemblage within mixed species colonies of nesting seabirds on patterns of genetic clustering within two species of multihost ectoparasitic lice. We use three genetic markers (one mitochondrial, COI, and two nuclear, EF1-alpha and wingless) and maximum likelihood phylogenetic trees to test whether (1) parasites show lineage sorting based on their host species; and (2) switching of lineages to the alternate host species depends on the immediate local species assemblage of individual hosts within a colony. Specifically, we examine the genetic structure of two louse species: Eidmanniella albescens, infecting both Nazca (Sula granti) and blue-footed boobies (Sula nebouxii), and Fregatiella aurifasciata, infecting both great (Fregata minor) and magnificent frigatebirds (Fregata magnificens). We found that host species identity was the only factor explaining the patterns of genetic structure in both parasites. In both cases, there is evident genetic differentiation depending on the host species. Thus, a revision of the taxonomy of these louse species is needed. One possible explanation of this pattern is extremely low louse migration rates between host species, perhaps influenced by fine-scale spatial separation of host species within mixed colonies, and low parasite infrapopulation numbers. PMID- 26380663 TI - Linking stream ecology with morphological variability in a native freshwater fish from semi-arid Australia. AB - Environmental variation is a potent force affecting phenotypic expression. While freshwater fishes have provided a compelling example of the link between the environment and phenotypic diversity, few studies have been conducted with arid zone fishes, particularly those that occur in geographically isolated regions where species typically inhabit intermittent and ephemeral creeks. We investigated morphological variation of a freshwater fish (the western rainbowfish, Melanotaenia australis) inhabiting creeks in the Pilbara region of northwest Australia to determine whether body shape variation correlated with local environmental characteristics, including water velocity, habitat complexity, predator presence, and food availability. We expected that the geographic isolation of creeks within this arid region would result in habitat specific morphological specializations. We used landmark-based geometric morphometrics to quantify the level of morphological variability in fish captured from 14 locations within three distinct subcatchments of a major river system. Western rainbowfish exhibited a range of morphologies, with variation in body depth accounting for a significant proportion (>42%) of the total variance in shape. Sexual dimorphism was also apparent, with males displaying deeper bodies than females. While the measured local habitat characteristics explained little of the observed morphological variation, fish displayed significant morphological differentiation at the level of the subcatchment. Local adaptation may partly explain the geographic patterns of body shape variation, but fine-scale genetic studies are required to disentangle the effects of genetic differentiation from environmentally determined phenotypic plasticity in body shape. Developing a better understanding of environment-phenotype relationships in species from arid regions will provide important insights into ecological and evolutionary processes in these unique and understudied habitats. PMID- 26380664 TI - Size matters: nest colonization patterns for twig-nesting ants. AB - Understanding the drivers of ant diversity and co-occurrence in agroecosystems is fundamental because ants participate in interactions that influence agroecosystem processes. Multiple local and regional factors influence ant community assembly.We examined local factors that influence the structure of a twig-nesting ant community in a coffee system in Mexico using an experimental approach. We investigated whether twig characteristics (nest entrance size and diversity of nest entrance sizes) and nest strata (canopy shade tree or coffee shrub) affected occupation, species richness, and community composition of twig-nesting ants and whether frequency of occupation of ant species varied with particular nest entrance sizes or strata.We conducted our study in a shaded coffee farm in Chiapas, Mexico, between March and June 2012. We studied ant nest colonization by placing artificial nests (bamboo twigs) on coffee shrubs and shade trees either in diverse or uniform treatments. We also examined whether differences in vegetation (no. of trees, canopy cover and coffee density) influenced nest colonization.We found 33 ant species occupying 73% of nests placed. Nest colonization did not differ with nest strata or size. Mean species richness of colonizing ants was significantly higher in the diverse nest size entrance treatment, but did not differ with nest strata. Community composition differed between strata and also between the diverse and uniform size treatments on coffee shrubs, but not on shade trees. Some individual ant species were more frequently found in certain nest strata and in nests with certain entrance sizes.Our results indicate that twig-nesting ants are nest-site limited, quickly occupy artificial nests of many sizes, and that trees or shrubs with twigs of a diversity of entrance sizes likely support higher ant species richness. Further, individual ant species more frequently occupy nests with different sized entrances promoting ant richness on individual coffee plants and trees. PMID- 26380665 TI - Dynamics of novel forests of Castilla elastica in Puerto Rico: from species to ecosystems. AB - Novel forests (NFs)-forests that contain a combination of introduced and native species-are a consequence of intense anthropogenic disturbances and the natural resilience of disturbed ecosystems. The extent to which NFs have similar forest function as comparable native secondary forests is a matter of debate in the scientific community. Little is known about the performance of individual species in those forests. This study focuses on the functional attributes of Castilla elastica NFs in Puerto Rico and on the differences between introduced and native species growing side by side in these forests. Rates of processes measured here were later compared with data from literature about NSFs. I hypothesize that juvenile plants of C. elastica in NFs have higher survival rate than those of native species and that C. elastica trees have faster biomass fluxes than native trees. To test the hypotheses, I measured survival rates of juvenile plants and tree growth and characterized the aboveground litter fluxes and storage. Although juvenile plants of native species displayed higher survival rates than those of C. elastica (53% vs. 28%), the latter was dominant in the understory (96%). Stand biomass growth rate was 2.0 +/- 0.4 (average +/- one standard deviation) Mg.ha( 1).year(-1) for the whole forest, and Guarea guidonia, a native species, exhibited the highest tree growth. Total litter fall was 9.6 +/- 0.5 Mg.ha( 1).year(-1), and mean litter standing stock was 4.4 +/- 0.1 Mg.ha(-1). Castilla elastica litter fall decomposed twice as fast as that of native species (5.8 +/- 1.1 vs. 3.03 +/- 1 k.year(-1)). Literature comparisons show that the present NFs differ in some rates of processes from NSFs. This study brings unique and detailed supporting data about the ecological dynamics under mature novel forest stands. Further comprehensive studies about NFs are important to strengthen the body of knowledge about the wide range of variation of emerging tropical ecosystems. Due to the large increase in the area covered by NFs, greater attention is needed to understand their functioning, delivery of ecological services and management requirements. PMID- 26380666 TI - Spore sensitivity to sunlight and freezing can restrict dispersal in wood-decay fungi. AB - Assessment of the costs and benefits of dispersal is central to understanding species' life-history strategies as well as explaining and predicting spatial population dynamics in the changing world. While mortality during active movement has received much attention, few have studied the costs of passive movement such as the airborne transport of fungal spores. Here, we examine the potential of extreme environmental conditions to cause dispersal mortality in wood-decay fungi. These fungi play a key role as decomposers and habitat creators in forest ecosystems and the populations of many species have declined due to habitat loss and fragmentation. We measured the effect of simulated solar radiation (including ultraviolet A and B) and freezing at -25 degrees C on the spore germinability of 17 species. Both treatments but especially sunlight markedly reduced spore germinability in most species, and species with thin-walled spores were particularly light sensitive. Extrapolating the species' laboratory responses to natural irradiance conditions, we predict that sunlight is a relevant source of dispersal mortality at least at larger spatial scales. In addition, we found a positive effect of spore size on spore germinability, suggesting a trade-off between dispersal distance and establishment. We conclude that freezing and particularly sunlight can be important sources of dispersal mortality in wood decay fungi which can make it difficult for some species to colonize isolated habitat patches and habitat edges. PMID- 26380667 TI - The avoidance strategy of environmental constraints by an aquatic plant Potamogeton alpinus in running waters. AB - Aquatic plants anchored in streams are under pressure from various constraints linked to the water flow and display strategies to prevent their damage or destruction. We assume that the responses of aquatic plants to fast-water flow are a manifestation of a trade-off consisting in either maximizing the resistance to damage (tolerance strategy) in minimizing the hydrodynamic forces (avoidance strategy), or both. Our main hypothesis was that Potamogeton alpinus demonstrate the avoidance strategy. We analyzed architecture traits of the modules of this clonal plant from slow- and fast-flowing streams. In fast-flowing waters, the avoidance strategy of P. alpinus is reflected by the following: (1) the presence of floating leaves that stabilize the vertical position of the stem and protect the inflorescence against immersion; (2) elongation of submerged leaves (weakens the pressure of water); and (3) shoot diameter reduction and increase in shoot density (weakens the pressure of water, increases shoot elasticity), and by contrast in slow-water flow include the following: (4) the absence of floating leaves in high intensity of light (avoiding unnecessary outlays on a redundant organ); (5) the presence of floating leaves in low intensity of light (avoidance of stress caused by an insufficient assimilation area of submerged leaves). PMID- 26380668 TI - Does Acacia dealbata express shade tolerance in Mediterranean forest ecosystems of South America? AB - The distribution of Acacia dealbata Link (Fabaceae) in its non-native range is associated with disturbed areas. However, the possibility that it can penetrate the native forest during the invasion process cannot be ruled out. This statement is supported by the fact that this species has been experimentally established successfully under the canopy of native forest. Nonetheless, it is unknown whether A. dealbata can express shade tolerance traits to help increase its invasive potential. We investigated the shade tolerance of A. dealbata under the canopy of two native forests and one non-native for three consecutive years, as well as its early growth and photosynthetic performance at low light intensities (9, 30, and 70 MUmol m(-2)sec(-1)) under controlled conditions. We found many A. dealbata plants surviving and growing under the canopy of native and non-native forests. The number of plants of this invasive species remained almost constant under the canopy of native forests during the years of study. However, the largest number of A. dealbata plants was found under the canopy of non-native forest. In every case, the distribution pattern varied with a highest density of plants in forest edges decreasing progressively toward the inside. Germination and early growth of A. dealbata were slow but successful at three low light intensities tested under controlled conditions. For all tested light regimes, we observed that in this species, most of the energy was dissipated by photochemical processes, in accordance with the high photosynthetic rates that this plant showed, despite the really low light intensities under which it was grown. Our study reveals that A. dealbata expressed shade tolerance traits under the canopy of native and non-native forests. This behavior is supported by the efficient photosynthetic performance that A. dealbata showed at low light intensities. Therefore, these results suggest that Mediterranean forest ecosystems of South America can become progressively invaded by A. dealbata and provide a basis for estimating the possible impacts that this invasive species can cause in these ecosystems in a timescale. PMID- 26380669 TI - Widespread positive but weak assortative mating by diet within stickleback populations. AB - Assortative mating - correlation between male and female traits - is common within populations and has the potential to promote genetic diversity and in some cases speciation. Despite its importance, few studies have sought to explain variation in the extent of assortativeness across populations. Here, we measure assortative mating based on an ecologically important trait, diet as inferred from stable isotopes, in 16 unmanipulated lake populations of three-spine stickleback. As predicted, we find a tendency toward positive assortment on the littoral-pelagic axis, although the magnitude is consistently weak. These populations vary relatively little in the strength of assortativeness, and what variation occurs is not explained by hypothesized drivers including habitat cosegregation, the potential for disruptive selection, costs to choosiness, and the strength of the relationship between diet and body size. Our results support recent findings that most assortative mating is positive, while suggesting that new approaches may be required to identify the environmental variables that drive the evolution of nonrandom mating within populations. PMID- 26380670 TI - Spatio-temporal variation in European starling reproductive success at multiple small spatial scales. AB - Understanding population dynamics requires spatio-temporal variation in demography to be measured across appropriate spatial and temporal scales. However, the most appropriate spatial scale(s) may not be obvious, few datasets cover sufficient time periods, and key demographic rates are often incompletely measured. Consequently, it is often assumed that demography will be spatially homogeneous within populations that lack obvious subdivision. Here, we quantify small-scale spatial and temporal variation in a key demographic rate, reproductive success (RS), within an apparently contiguous population of European starlings. We used hierarchical cluster analysis to define spatial clusters of nest sites at multiple small spatial scales and long-term data to test the hypothesis that small-scale spatio-temporal variation in RS occurred. RS was measured as the number of chicks alive ca. 12 days posthatch either per first brood or per nest site per breeding season (thereby incorporating multiple breeding attempts). First brood RS varied substantially among spatial clusters and years. Furthermore, the pattern of spatial variation was stable across years; some nest clusters consistently produced more chicks than others. Total seasonal RS also varied substantially among spatial clusters and years. However, the magnitude of variation was much larger and the pattern of spatial variation was no longer temporally consistent. Furthermore, the estimated magnitude of spatial variation in RS was greater at smaller spatial scales. We thereby demonstrate substantial spatial, temporal, and spatio-temporal variation in RS occurring at very small spatial scales. We show that the estimated magnitude of this variation depended on spatial scale and that spatio-temporal variation would not have been detected if season-long RS had not been measured. Such small-scale spatio temporal variation should be incorporated into empirical and theoretical treatments of population dynamics. PMID- 26380671 TI - Improving inferences from short-term ecological studies with Bayesian hierarchical modeling: white-headed woodpeckers in managed forests. AB - Pilot studies are often used to design short-term research projects and long-term ecological monitoring programs, but data are sometimes discarded when they do not match the eventual survey design. Bayesian hierarchical modeling provides a convenient framework for integrating multiple data sources while explicitly separating sample variation into observation and ecological state processes. Such an approach can better estimate state uncertainty and improve inferences from short-term studies in dynamic systems. We used a dynamic multistate occupancy model to estimate the probabilities of occurrence and nesting for white-headed woodpeckers Picoides albolarvatus in recent harvest units within managed forests of northern California, USA. Our objectives were to examine how occupancy states and state transitions were related to forest management practices, and how the probabilities changed over time. Using Gibbs variable selection, we made inferences using multiple model structures and generated model-averaged estimates. Probabilities of white-headed woodpecker occurrence and nesting were high in 2009 and 2010, and the probability that nesting persisted at a site was positively related to the snag density in harvest units. Prior-year nesting resulted in higher probabilities of subsequent occurrence and nesting. We demonstrate the benefit of forest management practices that increase the density of retained snags in harvest units for providing white-headed woodpecker nesting habitat. While including an additional year of data from our pilot study did not drastically alter management recommendations, it changed the interpretation of the mechanism behind the observed dynamics. Bayesian hierarchical modeling has the potential to maximize the utility of studies based on small sample sizes while fully accounting for measurement error and both estimation and model uncertainty, thereby improving the ability of observational data to inform conservation and management strategies. PMID- 26380672 TI - The ubiquity of phenotypic plasticity in plants: a synthesis. AB - Adaptation to heterogeneous environments can occur via phenotypic plasticity, but how often this occurs is unknown. Reciprocal transplant studies provide a rich dataset to address this issue in plant populations because they allow for a determination of the prevalence of plastic versus canalized responses. From 31 reciprocal transplant studies, we quantified the frequency of five possible evolutionary patterns: (1) canalized response-no differentiation: no plasticity, the mean phenotypes of the populations are not different; (2) canalized response population differentiation: no plasticity, the mean phenotypes of the populations are different; (3) perfect adaptive plasticity: plastic responses with similar reaction norms between populations; (4) adaptive plasticity: plastic responses with parallel, but not congruent reaction norms between populations; and (5) nonadaptive plasticity: plastic responses with differences in the slope of the reaction norms. The analysis included 362 records: 50.8% life-history traits, 43.6% morphological traits, and 5.5% physiological traits. Across all traits, 52% of the trait records were not plastic, and either showed no difference in means across sites (17%) or differed among sites (83%). Among the 48% of trait records that showed some sort of plasticity, 49.4% showed perfect adaptive plasticity, 19.5% adaptive plasticity, and 31% nonadaptive plasticity. These results suggest that canalized responses are more common than adaptive plasticity as an evolutionary response to environmental heterogeneity. PMID- 26380673 TI - Temporal dynamics of linkage disequilibrium in two populations of bighorn sheep. AB - Linkage disequilibrium (LD) is the nonrandom association of alleles at two markers. Patterns of LD have biological implications as well as practical ones when designing association studies or conservation programs aimed at identifying the genetic basis of fitness differences within and among populations. However, the temporal dynamics of LD in wild populations has received little empirical attention. In this study, we examined the overall extent of LD, the effect of sample size on the accuracy and precision of LD estimates, and the temporal dynamics of LD in two populations of bighorn sheep (Ovis canadensis) with different demographic histories. Using over 200 microsatellite loci, we assessed two metrics of multi-allelic LD, D', and chi ('2). We found that both populations exhibited high levels of LD, although the extent was much shorter in a native population than one that was founded via translocation, experienced a prolonged bottleneck post founding, followed by recent admixture. In addition, we observed significant variation in LD in relation to the sample size used, with small sample sizes leading to depressed estimates of the extent of LD but inflated estimates of background levels of LD. In contrast, there was not much variation in LD among yearly cross-sections within either population once sample size was accounted for. Lack of pronounced interannual variability suggests that researchers may not have to worry about interannual variation when estimating LD in a population and can instead focus on obtaining the largest sample size possible. PMID- 26380674 TI - Positive selection drives adaptive diversification of the 4-coumarate: CoA ligase (4CL) gene in angiosperms. AB - Lignin and flavonoids play a vital role in the adaption of plants to a terrestrial environment. 4-Coumarate: coenzyme A ligase (4CL) is a key enzyme of general phenylpropanoid metabolism which provides the precursors for both lignin and flavonoids biosynthesis. However, very little is known about how such essential enzymatic functions evolve and diversify. Here, we analyze 4CL sequence variation patterns in a phylogenetic framework to further identify the evolutionary forces that lead to functional divergence. The results reveal that lignin-biosynthetic 4CLs are under positive selection. The majority of the positively selected sites are located in the substrate-binding pocket and the catalytic center, indicating that nonsynonymous substitutions might contribute to the functional evolution of 4CLs for lignin biosynthesis. The evolution of 4CLs involved in flavonoid biosynthesis is constrained by purifying selection and maintains the ancestral role of the protein in response to biotic and abiotic factors. Overall, our results demonstrate that protein sequence evolution via positive selection is an important evolutionary force driving adaptive diversification in 4CL proteins in angiosperms. This diversification is associated with adaption to a terrestrial environment. PMID- 26380675 TI - Freshwater wetlands: fertile grounds for the invasive Phragmites australis in a climate change context. AB - Climate change will likely affect flooding regimes, which have a large influence on the functioning of freshwater riparian wetlands. Low water levels predicted for several fluvial systems make wetlands especially vulnerable to the spread of invaders, such as the common reed (Phragmites australis), one of the most invasive species in North America. We developed a model to map the distribution of potential germination grounds of the common reed in freshwater wetlands of the St. Lawrence River (Quebec, Canada) under current climate conditions and used this model to predict their future distribution under two climate change scenarios simulated for 2050. We gathered historical and recent (remote sensing) data on the distribution of common reed stands for model calibration and validation purposes, then determined the parameters controlling the species establishment by seed. A two-dimensional model and the identified parameters were used to simulate the current (2010) and future (2050) distribution of germination grounds. Common reed stands are not widespread along the St. Lawrence River (212 ha), but our model suggests that current climate conditions are already conducive to considerable further expansion (>16,000 ha). Climate change may also exacerbate the expansion, particularly if river water levels drop, which will expose large bare areas propitious to seed germination. This phenomenon may be particularly important in one sector of the river, where existing common reed stands could increase their areas by a factor of 100, potentially creating the most extensive reedbed complex in North America. After colonizing salt and brackishwater marshes, the common reed could considerably expand into the freshwater marshes of North America which cover several million hectares. The effects of common reed expansion on biodiversity are difficult to predict, but likely to be highly deleterious given the competitiveness of the invader and the biological richness of freshwater wetlands. PMID- 26380677 TI - Environmental effects on survival rates: robust regression, recovery planning and endangered Atlantic salmon. AB - Describing how population-level survival rates are influenced by environmental change becomes necessary during recovery planning to identify threats that should be the focus for future remediation efforts. However, the ways in which data are analyzed have the potential to change our ecological understanding and thus subsequent recommendations for remedial actions to address threats. In regression, distributional assumptions underlying short time series of survival estimates cannot be investigated a priori and data likely contain points that do not follow the general trend (outliers) as well as contain additional variation relative to an assumed distribution (overdispersion). Using juvenile survival data from three endangered Atlantic salmon Salmo salar L. populations in response to hydrological variation, four distributions for the response were compared using lognormal and generalized linear models (GLM). The influence of outliers as well as overdispersion was investigated by comparing conclusions from robust regressions with these lognormal models and GLMs. The analyses strongly supported the use of a lognormal distribution for survival estimates (i.e., modeling the instantaneous rate of mortality as the response) and would have led to ambiguity in the identification of significant hydrological predictors as well as low overall confidence in the predicted relationships if only GLMs had been considered. However, using robust regression to evaluate the effect of additional variation and outliers in the data relative to regression assumptions resulted in a better understanding of relationships between hydrological variables and survival that could be used for population-specific recovery planning. This manuscript highlights how a systematic analysis that explicitly considers what monitoring data represent and where variation is likely to come from is required in order to draw meaningful conclusions when analyzing changes in survival relative to environmental variation to aid in recovery planning. PMID- 26380676 TI - Quantitative genetics of plumage color: lifetime effects of early nest environment on a colorful sexual signal. AB - Phenotypic differences among individuals are often linked to differential survival and mating success. Quantifying the relative influence of genetic and environmental variation on phenotype allows evolutionary biologists to make predictions about the potential for a given trait to respond to selection and various aspects of environmental variation. In particular, the environment individuals experience during early development can have lasting effects on phenotype later in life. Here, we used a natural full-sib/half-sib design as well as within-individual longitudinal analyses to examine genetic and various environmental influences on plumage color. We find that variation in melanin based plumage color - a trait known to influence mating success in adult North American barn swallows (Hirundo rustica erythrogaster) - is influenced by both genetics and aspects of the developmental environment, including variation due to the maternal phenotype and the nest environment. Within individuals, nestling color is predictive of adult color. Accordingly, these early environmental influences are relevant to the sexually selected plumage color variation in adults. Early environmental conditions appear to have important lifelong implications for individual reproductive performance through sexual signal development in barn swallows. Our results indicate that feather color variation conveys information about developmental conditions and maternal care alleles to potential mates in North American barn swallows. Melanin-based colors are used for sexual signaling in many organisms, and our study suggests that these signals may be more sensitive to environmental variation than previously thought. PMID- 26380678 TI - Indirect effects of habitat disturbance on invasion: nutritious litter from a grazing resistant plant favors alien over native Collembola. AB - Biological invasions are major threats to biodiversity, with impacts that may be compounded by other forms of environmental change. Observations of high density of the invasive springtail (Collembola), Hypogastrura manubrialis in heavily grazed renosterveld vegetation in the Western Cape, South Africa, raised the question of whether the invasion was favored by changes in plant litter quality associated with habitat disturbance in this vegetation type. To examine the likely mechanisms underlying the high abundance of H. manubrialis, cages with three types of naturally occurring litter with different nutrient content were placed out in the area and collected after different periods of time. Hypogastrura manubrialis was mainly found in the nutrient-rich litter of the yellowbush (Galenia africana), which responds positively to disturbance in the form of overgrazing. This suggests that invasion may have been facilitated by a positive interaction with this grazing resistant plant. By contrast, indigenous Collembola were least abundant in yellowbush litter. Negative correlations between high abundance of H. manubrialis and the abundance and diversity of other species suggest that competitive interactions might underlie low abundance of these other species at the patch level. Group behavior enables H. manubrialis to utilize efficiently this ephemeral, high quality resource, and might improve its competitive ability. The results suggest that interactions among environmental change drivers may lead to unforeseen invasion effects. H. manubrialis is not likely to be very successful in un-grazed renosterveld, but in combination with grazing, favoring the nutrient-rich yellowbush, it may become highly invasive. Field manipulations are required to fully verify these conclusions. PMID- 26380680 TI - Contrasting demographic history and gene flow patterns of two mangrove species on either side of the Central American Isthmus. AB - Comparative phylogeography offers a unique opportunity to understand the interplay between past environmental events and life-history traits on diversification of unrelated but co-distributed species. Here, we examined the effects of the quaternary climate fluctuations and palaeomarine currents and present-day marine currents on the extant patterns of genetic diversity in the two most conspicuous mangrove species of the Neotropics. The black (Avicennia germinans, Avicenniaceae) and the red (Rhizophora mangle, Rhizophoraceae) mangroves have similar geographic ranges but are very distantly related and show striking differences on their life-history traits. We sampled 18 Atlantic and 26 Pacific locations for A. germinans (N = 292) and R. mangle (N = 422). We performed coalescence simulations using microsatellite diversity to test for evidence of population change associated with quaternary climate fluctuations. In addition, we examined whether patterns of genetic variation were consistent with the directions of major marine (historical and present day) currents in the region. Our demographic analysis was grounded within a phylogeographic framework provided by the sequence analysis of two chloroplasts and one flanking microsatellite region in a subsample of individuals. The two mangrove species shared similar biogeographic histories including: (1) strong genetic breaks between Atlantic and Pacific ocean basins associated with the final closure of the Central American Isthmus (CAI), (2) evidence for simultaneous population declines between the mid-Pleistocene and early Holocene, (3) asymmetric historical migration with higher gene flow from the Atlantic to the Pacific oceans following the direction of the palaeomarine current, and (4) contemporary gene flow between West Africa and South America following the major Atlantic Ocean currents. Despite the remarkable differences in life-history traits of mangrove species, which should have had a strong influence on seed dispersal capability and, thus, population connectivity, we found that vicariant events, climate fluctuations and marine currents have shaped the distribution of genetic diversity in strikingly similar ways. PMID- 26380679 TI - Ecological connectivity assessment in a strongly structured fire salamander (Salamandra salamandra) population. AB - Small populations are more prone to extinction if the dispersal among them is not adequately maintained by ecological connections. The degree of isolation between populations could be evaluated measuring their genetic distance, which depends on the respective geographic (isolation by distance, IBD) and/or ecological (isolation by resistance, IBR) distances. The aim of this study was to assess the ecological connectivity of fire salamander Salamandra salamandra populations by means of a landscape genetic approach. The species lives in broad-leaved forest ecosystems and is particularly affected by fragmentation due to its habitat selectivity and low dispersal capability. We analyzed 477 biological samples collected in 47 sampling locations (SLs) in the mainly continuous populations of the Prealpine and Eastern foothill lowland (PEF) and 10 SLs in the fragmented populations of the Western foothill (WF) lowland of Lombardy (northern Italy). Pairwise genetic distances (Chord distance, DC) were estimated from allele frequencies of 16 microsatellites loci. Ecological distances were calculated using one of the most promising methodology in landscape genetics studies, the circuit theory, applied to habitat suitability maps. We realized two habitat suitability models: one without barriers (EcoD) and a second one accounting for the possible barrier effect of main roads (EcoDb). Mantel tests between distance matrices highlighted how the Log-DC in PEF populations was related to log transformed geographic distance (confirming a prevalence of IBD), while it was explained by the Log-EcoD, and particularly by the Log-EcoDb, in WF populations, even when accounting for the confounding effect of geographic distance (highlighting a prevalence of IBR). Moreover, we also demonstrated how considering the overall population, the effect of Euclidean or ecological distances on genetic distances acting at the level of a single group (PEF or WF populations) could not be detected, when population are strongly structured. PMID- 26380681 TI - Limited catching bias in a wild population of birds with near-complete census information. AB - Animal research often relies on catching wild animals; however, individuals may have different trappability, and this can generate bias. We studied bias in mist netting, the main method for catching wild birds. The unusually high resighting rate in our study population-house sparrows (Passer domesticus) on Lundy Island (England)-allowed us to obtain accurate estimates of the population size. This unique situation enabled us to test for catching bias in mist netting using deviations from the expected Poisson distribution. There was no evidence that a fraction of the birds in the population consistently remained uncaught. However, we detected a different bias: More birds than expected were captured only once within a year. This bias probably resulted from a mixture of fieldworkers sometimes ignoring rapid recaptures and birds becoming net shy after their first capture. We had sufficient statistical power with the available data to detect a substantial uncaught fraction. Therefore, our data are probably unbiased toward catching specific individuals from our population. Our analyses demonstrate that intensively monitored natural insular populations, in which population size can be estimated precisely, provide the potential to address important unanswered questions without concerns about a fraction of the population remaining uncaught. Our approach can help researchers to test for catching bias in closely monitored wild populations for which reliable estimates of population size and dispersal are available. PMID- 26380682 TI - Comparative genetic diversity in a sample of pony breeds from the U.K. and North America: a case study in the conservation of global genetic resources. AB - Most species exist as subdivided ex situ daughter population(s) derived from a single original group of individuals. Such subdivision occurs for many reasons both natural and manmade. Traditional British and Irish pony breeds were introduced to North America (U.S.A. and Canada) within the last 150 years, and subsequently equivalent breed societies were established. We have analyzed selected U.K. and North American equivalent pony populations as a case study for understanding the relationship between putative source and derived subpopulations. Diversity was measured using mitochondrial DNA and a panel of microsatellite markers. Genetic signatures differed between the North American subpopulations according to historical management processes. Founder effect and stochastic drift was apparent, particularly pronounced in some breeds, with evidence of admixture of imported mares of different North American breeds. This demonstrates the importance of analysis of subpopulations to facilitate understanding the genetic effects of past management practices and to lead to informed future conservation strategies. PMID- 26380683 TI - Experimental evidence that wildflower strips increase pollinator visits to crops. AB - Wild bees provide a free and potentially diverse ecosystem service to farmers growing pollination-dependent crops. While many crops benefit from insect pollination, soft fruit crops, including strawberries are highly dependent on this ecosystem service to produce viable fruit. However, as a result of intensive farming practices and declining pollinator populations, farmers are increasingly turning to commercially reared bees to ensure that crops are adequately pollinated throughout the season. Wildflower strips are a commonly used measure aimed at the conservation of wild pollinators. It has been suggested that commercial crops may also benefit from the presence of noncrop flowers; however, the efficacy and economic benefits of sowing flower strips for crops remain relatively unstudied. In a study system that utilizes both wild and commercial pollinators, we test whether wildflower strips increase the number of visits to adjacent commercial strawberry crops by pollinating insects. We quantified this by experimentally sowing wildflower strips approximately 20 meters away from the crop and recording the number of pollinator visits to crops with, and without, flower strips. Between June and August 2013, we walked 292 crop transects at six farms in Scotland, recording a total of 2826 pollinators. On average, the frequency of pollinator visits was 25% higher for crops with adjacent flower strips compared to those without, with a combination of wild and commercial bumblebees (Bombus spp.) accounting for 67% of all pollinators observed. This effect was independent of other confounding effects, such as the number of flowers on the crop, date, and temperature. Synthesis and applications. This study provides evidence that soft fruit farmers can increase the number of pollinators that visit their crops by sowing inexpensive flower seed mixes nearby. By investing in this management option, farmers have the potential to increase and sustain pollinator populations over time. PMID- 26380684 TI - The challenge of accurately documenting bee species richness in agroecosystems: bee diversity in eastern apple orchards. AB - Bees are important pollinators of agricultural crops, and bee diversity has been shown to be closely associated with pollination, a valuable ecosystem service. Higher functional diversity and species richness of bees have been shown to lead to higher crop yield. Bees simultaneously represent a mega-diverse taxon that is extremely challenging to sample thoroughly and an important group to understand because of pollination services. We sampled bees visiting apple blossoms in 28 orchards over 6 years. We used species rarefaction analyses to test for the completeness of sampling and the relationship between species richness and sampling effort, orchard size, and percent agriculture in the surrounding landscape. We performed more than 190 h of sampling, collecting 11,219 specimens representing 104 species. Despite the sampling intensity, we captured <75% of expected species richness at more than half of the sites. For most of these, the variation in bee community composition between years was greater than among sites. Species richness was influenced by percent agriculture, orchard size, and sampling effort, but we found no factors explaining the difference between observed and expected species richness. Competition between honeybees and wild bees did not appear to be a factor, as we found no correlation between honeybee and wild bee abundance. Our study shows that the pollinator fauna of agroecosystems can be diverse and challenging to thoroughly sample. We demonstrate that there is high temporal variation in community composition and that sites vary widely in the sampling effort required to fully describe their diversity. In order to maximize pollination services provided by wild bee species, we must first accurately estimate species richness. For researchers interested in providing this estimate, we recommend multiyear studies and rarefaction analyses to quantify the gap between observed and expected species richness. PMID- 26380685 TI - Early subtropical forest growth is driven by community mean trait values and functional diversity rather than the abiotic environment. AB - While functional diversity (FD) has been shown to be positively related to a number of ecosystem functions including biomass production, it may have a much less pronounced effect than that of environmental factors or species-specific properties. Leaf and wood traits can be considered particularly relevant to tree growth, as they reflect a trade-off between resources invested into growth and persistence. Our study focussed on the degree to which early forest growth was driven by FD, the environment (11 variables characterizing abiotic habitat conditions), and community-weighted mean (CWM) values of species traits in the context of a large-scale tree diversity experiment (BEF-China). Growth rates of trees with respect to crown diameter were aggregated across 231 plots (hosting between one and 23 tree species) and related to environmental variables, FD, and CWM, the latter two of which were based on 41 plant functional traits. The effects of each of the three predictor groups were analyzed separately by mixed model optimization and jointly by variance partitioning. Numerous single traits predicted plot-level tree growth, both in the models based on CWMs and FD, but none of the environmental variables was able to predict tree growth. In the best models, environment and FD explained only 4 and 31% of variation in crown growth rates, respectively, while CWM trait values explained 42%. In total, the best models accounted for 51% of crown growth. The marginal role of the selected environmental variables was unexpected, given the high topographic heterogeneity and large size of the experiment, as was the significant impact of FD, demonstrating that positive diversity effects already occur during the early stages in tree plantations. PMID- 26380686 TI - Phylogenetic and ecological patterns in nighttime transpiration among five members of the genus Rubus co-occurring in western Oregon. AB - Nighttime transpiration is a substantial portion of ecosystem water budgets, but few studies compare water use of closely related co-occurring species in a phylogenetic context. Nighttime transpiration can range up to 69% of daytime rates and vary between species, ecosystem, and functional type. We examined leaf level daytime and nighttime gas exchange of five species of the genus Rubus co occurring in the Pacific Northwest of western North America in a greenhouse common garden. Contrary to expectations, nighttime transpiration was not correlated to daytime water use. Nighttime transpiration showed pronounced phylogenetic signals, but the proportion of variation explained by different phylogenetic groupings varied across datasets. Leaf osmotic water potential, water potential at turgor loss point, stomatal size, and specific leaf area were correlated with phylogeny but did not readily explain variation in nighttime transpiration. Patterns in interspecific variation as well as a disconnect between rates of daytime and nighttime transpiration suggest that variation in nighttime water use may be at least partly driven by genetic factors independent of those that control daytime water use. Future work with co-occurring congeneric systems is needed to establish the generality of these results and may help determine the mechanism driving interspecific variation in nighttime water use. PMID- 26380687 TI - Population structure of the Indonesian giant tiger shrimp Penaeus monodon: a window into evolutionary similarities between paralogous mitochondrial DNA sequences and their genomes. AB - Here we used both microsatellites and mtCR (mitochondrial DNA control region) sequences as genetic markers to examine the genetic diversity and population structure of Penaeus monodon shrimp from six Indonesian regions. The microsatellite data showed that shrimp from the Indian and the Pacific Ocean were genetically distinct from each other. It has been reported previously that P. monodon mtCR sequences from the Indo-Pacific group into two major paralogous clades of unclear origin. Here we show that the population structure inferred from mtCR sequences matches the microsatellite-based population structure for one of these clades. This is consistent with the notion that this mtCR clade shares evolutionary history with nuclear DNA and may thus represent nuclear mitochondrial pseudogenes (Numts). PMID- 26380688 TI - Individual variation in parental workload and breeding productivity in female European starlings: is the effort worth it? AB - We analyzed individual variation in work load (nest visit rate) during chick rearing, and the consequences of this variation in terms of breeding productivity, in a highly synchronous breeder, the European starling (Sturnus vulgaris) focusing on female birds. There was marked (10- to 16-fold) variation in total, female and male nest visit rates, among individuals, but individual variation in female nest visit rate was independent of environment (rainfall, temperature) and metrics of individual quality (laying date, clutch size, amount of male provisioning help), and was only weakly associated with chick demand (i.e., day 6 brood size). Female nest visit rate was independent of date and experimentally delayed birds provisioned at the same rate as peak-nesting birds; supporting a lack of effect of date per se. Brood size at fledging was positively but weakly related to total nest visit rate (male + female), with >fivefold variation in nest visit rate for any given brood size, and in females brood size at fledging and chick mass at fledging were independent of female nest visit rate, that is, individual variation in workload was not associated with higher productivity. Nevertheless, nest visit rate in females was repeatable among consecutive days (6-8 posthatching), and between peak (first) and second broods, but not among years. Our data suggest that individual females behave as if committed to a certain level of parental care at the outset of their annual breeding attempt, but this varies among years, that is, behavior is not fixed throughout an individual's life but represents an annually variable decision. We suggest females are making predictable decisions about their workload during provisioning that maximizes their overall fitness based on an integration of information on their current environment (although these cues currently remain unidentified). PMID- 26380689 TI - Quantification of correlational selection on thermal physiology, thermoregulatory behavior, and energy metabolism in lizards. AB - Phenotypic selection is widely accepted as the primary cause of adaptive evolution in natural populations, but selection on complex functional properties linking physiology, behavior, and morphology has been rarely quantified. In ectotherms, correlational selection on thermal physiology, thermoregulatory behavior, and energy metabolism is of special interest because of their potential coadaptation. We quantified phenotypic selection on thermal sensitivity of locomotor performance (sprint speed), thermal preferences, and resting metabolic rate in captive populations of an ectothermic vertebrate, the common lizard, Zootoca vivipara. No correlational selection between thermal sensitivity of performance, thermoregulatory behavior, and energy metabolism was found. A combination of high body mass and resting metabolic rate was positively correlated with survival and negatively correlated with fecundity. Thus, different mechanisms underlie selection on metabolism in lizards with small body mass than in lizards with high body mass. In addition, lizards that selected the near average preferred body temperature grew faster that their congeners. This is one of the few studies that quantifies significant correlational selection on a proxy of energy expenditure and stabilizing selection on thermoregulatory behavior. PMID- 26380690 TI - Living in isolation - population structure, reproduction, and genetic variation of the endangered plant species Dianthus gratianopolitanus (Cheddar pink). AB - The endangered plant species Dianthus gratianopolitanus exhibits a highly fragmented distribution range comprising many isolated populations. Based upon this pattern of distribution, we selected a study region in Switzerland with a lower magnitude of isolation (Swiss Jura) and another study region in Germany with a higher degree of isolation (Franconian Jura). In each region, we chose ten populations to analyze population structure, reproduction, and genetic variation in a comparative approach. Therefore, we determined population density, cushion size, and cushion density to analyze population structure, investigated reproductive traits, including number of flowers, capsules, and germination rate, and analyzed amplified fragment length polymorphisms to study genetic variation. Population and cushion density were credibly higher in German than in Swiss populations, whereas reproductive traits and genetic variation within populations were similar in both study regions. However, genetic variation among populations and isolation by distance were stronger in Germany than in Switzerland. Generally, cushion size and density as well as flower and capsule production increased with population size and density, whereas genetic variation decreased with population density. In contrast to our assumptions, we observed denser populations and cushions in the region with the higher magnitude of isolation, whereas reproductive traits and genetic variation within populations were comparable in both regions. This corroborates the assumption that stronger isolation must not necessarily result in the loss of fitness and genetic variation. Furthermore, it supports our conclusion that the protection of strongly isolated populations contributes essentially to the conservation of a species' full evolutionary potential. PMID- 26380691 TI - An experimental test on time constraint and sexual conflict over parental care. AB - Because parental care is costly, a sexual conflict between parents over parental investment is expected to arise. Parental care behavior is an adaptive decision, involving trade-offs between remating, and consequently desertion of the brood, and continuing parental effort. If the main advantage of desertion is remating, then this will be a time constraint, because the deserting individual will require a certain minimum period of time to breed again in the same breeding season. So, a short breeding season should force certain individuals to desert the first brood to have enough time to successfully complete their second breeding attempt. The rock sparrow, Petronia petronia, is an unusual species in which brood desertion can occur in both sexes and the breeding season is quite short so it is a good species to investigate the role of time constraint on brood desertion. For 3 years, I investigated the brood desertion modality of the rock sparrow. Then, for 2 years, I removed a group of experimental nest boxes during the autumn. Later, I re-installed the experimental nest boxes after the start of the breeding season (2 weeks after the first egg was laid), mimicking a shortening of the breeding season for the (experimental) pairs that used experimental nest boxes. I found that in the experimental pairs, the percentage of deserting individuals was significantly higher than in the control groups, and the deserting individuals were older females. This experiment adds to our knowledge of timing of reproduction effects on individual decisions to desert by showing that a short and delayed breeding season may have different effects on males and females. To my knowledge, this is the first experimental study that demonstrates a direct link between time constraint and brood desertion. PMID- 26380692 TI - Candidate gene-environment interactions and their relationships with timing of breeding in a wild bird population. AB - Monitoring and predicting evolutionary changes underlying current environmental modifications are complex challenges. Recent approaches to achieve these objectives include assessing the genetic variation and effects of candidate genes on traits indicating adaptive potential. In birds, for example, short tandem repeat polymorphism at four candidate genes (CLOCK, NPAS2, ADCYAP1, and CREB1) has been linked to variation in phenological traits such as laying date and timing of migration. However, our understanding of their importance as evolutionary predictors is still limited, mainly because the extent of genotype environment interactions (GxE) related to these genes has yet to be assessed. Here, we studied a population of Tree swallow (Tachycineta bicolor) over 4 years in southern Quebec (Canada) to assess the relationships between those four candidate genes and two phenological traits related to reproduction (laying date and incubation duration) and also determine the importance of GxE in this system. Our results showed that NPAS2 female genotypes were nonrandomly distributed across the study system and formed a longitudinal cline with longer genotypes located to the east. We observed relationships between length polymorphism at all candidate genes and laying date and/or incubation duration, and most of these relationships were affected by environmental variables (breeding density, latitude, or temperature). In particular, the positive relationships detected between laying date and both CLOCK and NPAS2 female genotypes were variable depending on breeding density. Our results suggest that all four candidate genes potentially affect timing of breeding in birds and that GxE are more prevalent and important than previously reported in this context. PMID- 26380693 TI - Insect responses to host plant provision beyond natural boundaries: latitudinal and altitudinal variation in a Chinese fig wasp community. AB - Many plants are grown outside their natural ranges. Plantings adjacent to native ranges provide an opportunity to monitor community assembly among associated insects and their parasitoids in novel environments, to determine whether gradients in species richness emerge and to examine their consequences for host plant reproductive success. We recorded the fig wasps (Chalcidoidea) associated with a single plant resource (ovules of Ficus microcarpa) along a 1200 km transect in southwest China that extended for 1000 km beyond the tree's natural northern range margin. The fig wasps included the tree's agaonid pollinator and other species that feed on the ovules or are their parasitoids. Phytophagous fig wasps (12 species) were more numerous than parasitoids (nine species). The proportion of figs occupied by fig wasps declined with increasing latitude, as did the proportion of utilized ovules in occupied figs. Species richness, diversity, and abundance of fig wasps also significantly changed along both latitudinal and altitudinal gradients. Parasitoids declined more steeply with latitude than phytophages. Seed production declined beyond the natural northern range margin, and at high elevation, because pollinator fig wasps became rare or absent. This suggests that pollinator climatic tolerances helped limit the tree's natural distribution, although competition with another species may have excluded pollinators at the highest altitude site. Isolation by distance may prevent colonization of northern sites by some fig wasps and act in combination with direct and host-mediated climatic effects to generate gradients in community composition, with parasitoids inherently more sensitive because of declines in the abundance of potential hosts. PMID- 26380694 TI - Induced responses to grazing by an insect herbivore (Acentria ephemerella) in an immature macrophyte (Myriophyllum spicatum): an isotopic study. AB - While the mechanisms by which adult terrestrial plants deploy constitutive and induced responses to grazing pressure are well known, the means by which young aquatic plants defend themselves from herbivory are little studied. This study addresses nitrogen transport in the aquatic angiosperm Myriophyllum spicatum in response to herbivore exposure. Nitrogen tracers were used to monitor nitrogen uptake and reallocation in young plants in response to grazing by the generalist insect herbivore Acentria ephemerella. Total nitrogen content (N%) and patterns of nitrogen uptake and allocation (delta(15)N) were assessed in various plant tissues after 24 and 48 h. Following 24 h exposure to herbivore damage (Experiment 1), nitrogen content of plant apices was significantly elevated. This rapid early reaction may be an adaptation allowing the grazer to be sated as fast as possible, or indicate the accumulation of nitrogenous defense chemicals. After 48 h (Experiment 2), plants' tips showed depletion in nitrogen levels of ca. 600/00 in stem sections vulnerable to grazing. In addition, nitrogen uptake by grazed and grazing-prone upper plant parts was reduced and nutrient allocation into the relatively secure lower parts increased. The results point to three conclusions: (1) exposure to an insect herbivore induces a similar response in immature M. spicatum as previously observed in mature terrestrial species, namely a rapid (within 48 h) reduction in the nutritional value (N%) of vulnerable tissues, (2) high grazing intensity (100% of growing tips affected) did not limit the ability of young plants to induce resistance; and (3) young plants exposed to herbivory exhibit different patterns of nutrient allocation in vulnerable and secure tissues. These results provide evidence of induced defense and resource reallocation in immature aquatic macrophytes which is in line with the responses shown for mature aquatic macrophytes and terrestrial plants. PMID- 26380695 TI - American pika in a low-elevation lava landscape: expanding the known distribution of a temperature-sensitive species. AB - In 2010, the American pika (Ochotona princeps fenisex) was denied federal protection based on limited evidence of persistence in low-elevation environments. Studies in nonalpine areas have been limited to relatively few environments, and it is unclear whether patterns observed elsewhere (e.g., Bodie, CA) represent other nonalpine habitats. This study was designed to establish pika presence in a new location, determine distribution within the surveyed area, and evaluate influences of elevation, vegetation, lava complexity, and distance to habitat edge on pika site occupancy. In 2011 and 2012, we conducted surveys for American pika on four distinct subalpine lava flows of Newberry National Volcanic Monument, Oregon, USA. Field surveys were conducted at predetermined locations within lava flows via silent observation and active searching for pika sign. Site habitat characteristics were included as predictors of occupancy in multinomial regression models. Above and belowground temperatures were recorded at a subsample of pika detection sites. Pika were detected in 26% (2011) and 19% (2012) of survey plots. Seventy-four pika were detected outside survey plot boundaries. Lava complexity was the strongest predictor of pika occurrence, where pika were up to seven times more likely to occur in the most complicated lava formations. Pika were two times more likely to occur with increasing elevation, although they were found at all elevations in the study area. This study expands the known distribution of the species and provides additional evidence for persistence in nonalpine habitats. Results partially support the predictive occupancy model developed for pika at Craters of the Moon National Monument, another lava environment. Characteristics of the lava environment clearly influence pika site occupancy, but habitat variables reported as important in other studies were inconclusive here. Further work is needed to gain a better understanding of the species' current distribution and ability to persist under future climate conditions. PMID- 26380696 TI - Tracking changes in life-history traits related to unnecessary virulence in a plant-parasitic nematode. AB - Evaluating trade-offs in life-history traits of plant pathogens is essential to understand the evolution and epidemiology of diseases. In particular, virulence costs when the corresponding host resistance gene is lacking play a major role in the adaptive biology of pathogens and contribute to the maintenance of their genetic diversity. Here, we investigated whether life-history traits directly linked to the establishment of plant-nematode interactions, that is, ability to locate and move toward the roots of the host plant, and to invade roots and develop into mature females, are affected in Meloidogyne incognita lines virulent against the tomato Mi-1.2 resistance gene. Virulent and avirulent near-isogenic lines only differing in their capacity to reproduce or not on resistant tomatoes were compared in single inoculation or pairwise competition experiments. Data highlighted (1) a global lack of trade-off in traits associated with unnecessary virulence with respect to the nematode ability to successfully infest plant roots and (2) variability in these traits when the genetic background of the nematode is considered irrespective of its (a)virulence status. These data suggest that the variation detected here is independent from the adaptation of M. incognita to host resistance, but rather reflects some genetic polymorphism in this asexual organism. PMID- 26380697 TI - An example of phenotypic adherence to the island rule? - Anticosti gray jays are heavier but not structurally larger than mainland conspecifics. AB - The island rule refers to the tendency of small vertebrates to become larger when isolated on islands and the frequent dwarfing of large forms. It implies genetic control, and a necessary linkage, of size and body-mass differences between insular and mainland populations. To examine the island rule, we compared body size and mass of gray jays (Perisoreus canadensis) on Anticosti Island, Quebec, located in the Gulf of St. Lawrence, with three mainland populations (2 in Quebec and 1 in Ontario). Although gray jays on Anticosti Island were ca 10% heavier, they were not structurally larger, than the three mainland populations. This suggests that Anticosti jays are not necessarily genetically distinct from mainland gray jays and that they may have achieved their greater body masses solely through packing more mass onto mainland-sized body frames. As such, they may be the first-known example of a proposed, purely phenotypic initial step in the adherence to the island rule by an insular population. Greater jay body mass is probably advantageous in Anticosti's high-density, intensely competitive social environment that may have resulted from the island's lack of mammalian nest predators. PMID- 26380698 TI - Host range and community structure of avian nest parasites in the genus Philornis (Diptera: Muscidae) on the island of Trinidad. AB - Parasite host range can be influenced by physiological, behavioral, and ecological factors. Combining data sets on host-parasite associations with phylogenetic information of the hosts and the parasites involved can generate evolutionary hypotheses about the selective forces shaping host range. Here, we analyzed associations between the nest-parasitic flies in the genus Philornis and their host birds on Trinidad. Four of ten Philornis species were only reared from one species of bird. Of the parasite species with more than one host bird species, P. falsificus was the least specific and P. deceptivus the most specific attacking only Passeriformes. Philornis flies in Trinidad thus include both specialists and generalists, with varying degrees of specificity within the generalists. We used three quantities to more formally compare the host range of Philornis flies: the number of bird species attacked by each species of Philornis, a phylogenetically informed host specificity index (Poulin and Mouillot's S TD), and a branch length-based S TD. We then assessed the phylogenetic signal of these measures of host range for 29 bird species. None of these measures showed significant phylogenetic signal, suggesting that clades of Philornis did not differ significantly in their ability to exploit hosts. We also calculated two quantities of parasite species load for the birds - the parasite species richness, and a variant of the S TD index based on nodes rather than on taxonomic levels - and assessed the signal of these measures on the bird phylogeny. We did not find significant phylogenetic signal for the parasite species load or the node-based S TD index. Finally, we calculated the parasite associations for all bird pairs using the Jaccard index and regressed these similarity values against the number of nodes in the phylogeny separating bird pairs. This analysis showed that Philornis on Trinidad tend to feed on closely related bird species more often than expected by chance. PMID- 26380699 TI - Persistence at distributional edges: Columbia spotted frog habitat in the arid Great Basin, USA. AB - A common challenge in the conservation of broadly distributed, yet imperiled species is understanding which factors facilitate persistence at distributional edges, locations where populations are often vulnerable to extirpation due to changes in climate, land use, or distributions of other species. For Columbia spotted frogs (Rana luteiventris) in the Great Basin (USA), a genetically distinct population segment of conservation concern, we approached this problem by examining (1) landscape-scale habitat availability and distribution, (2) water body-scale habitat associations, and (3) resource management-identified threats to persistence. We found that areas with perennial aquatic habitat and suitable climate are extremely limited in the southern portion of the species' range. Within these suitable areas, native and non-native predators (trout and American bullfrogs [Lithobates catesbeianus]) are widespread and may further limit habitat availability in upper- and lower-elevation areas, respectively. At the water body scale, spotted frog occupancy was associated with deeper sites containing abundant emergent vegetation and nontrout fish species. Streams with American beaver (Castor canadensis) frequently had these structural characteristics and were significantly more likely to be occupied than ponds, lakes, streams without beaver, or streams with inactive beaver ponds, highlighting the importance of active manipulation of stream environments by beaver. Native and non-native trout reduced the likelihood of spotted frog occupancy, especially where emergent vegetation cover was sparse. Intensive livestock grazing, low aquatic connectivity, and ephemeral hydroperiods were also negatively associated with spotted frog occupancy. We conclude that persistence of this species at the arid end of its range has been largely facilitated by habitat stability (i.e., permanent hydroperiod), connectivity, predator-free refugia, and a commensalistic interaction with an ecosystem engineer. Beaver-induced changes to habitat quality, stability, and connectivity may increase spotted frog population resistance and resilience to seasonal drought, grazing, non-native predators, and climate change, factors which threaten local or regional persistence. PMID- 26380700 TI - Context matters: sexual signaling loss in digital organisms. AB - Sexual signals are important in attracting and choosing mates; however, these signals and their associated preferences are often costly and frequently lost. Despite the prevalence of signaling system loss in many taxa, the factors leading to signal loss remain poorly understood. Here, we test the hypothesis that complexity in signal loss scenarios is due to the context-dependent nature of the many factors affecting signal loss itself. Using the Avida digital life platform, we evolved 50 replicates of ~250 lineages, each with a unique combination of parameters, including whether signaling is obligate or facultative; genetic linkage between signaling and receiving genes; population size; and strength of preference for signals. Each of these factors ostensibly plays a crucial role in signal loss, but was found to do so only under specific conditions. Under obligate signaling, genetic linkage, but not population size, influenced signal loss; under facultative signaling, genetic linkage does not have significant influence. Somewhat surprisingly, only a total loss of preference in the obligate signaling populations led to total signal loss, indicating that even a modest amount of preference is enough to maintain signaling systems. Strength of preference proved to be the strongest single force preventing signal loss, as it consistently overcame the potential effects of drift within our study. Our findings suggest that signaling loss is often dependent on not just preference for signals, population size, and genetic linkage, but also whether signals are required to initiate mating. These data provide an understanding of the factors (and their interactions) that may facilitate the maintenance of sexual signals. PMID- 26380701 TI - Baiting improves CPUE in nine-spined stickleback (Pungitius pungitius) minnow trap fishery. AB - Whether or not baiting influences stickleback catch per unit effort (CPUE) remains a matter of debate among stickleback researchers: While the opinions about the impact of baiting on CPUE differ, supporting quantitative data are scarce. The effect of baiting and trap type on nine-spined stickleback (Pungitius pungitius) CPUE was studied in a field experiment conducted over four consecutive days in a small pond in northeastern Finland. The results show that baited traps yielded better (mean CPUE = 1.24 fish/trap/d) catches than unbaited traps (mean CPUE = 0.66); however, there were also differences in CPUE depending on the type of collapsible trap that was used. The trap type effect on CPUE seemed to differ among age classes - the finer meshed trap caught more young-of-the-year fish than the coarse-meshed one, whereas the opposite was true for the older and larger individuals. The results agree with those of an earlier more restricted study conducted in the same locality: Together, these results provide strong evidence for the positive impact of baiting on nine-spined stickleback CPUE. PMID- 26380703 TI - Interrelated effects of mycorrhiza and free-living nitrogen fixers cascade up to aboveground herbivores. AB - Aboveground plant performance is strongly influenced by belowground microorganisms, some of which are pathogenic and have negative effects, while others, such as nitrogen-fixing bacteria and arbuscular mycorrhizal fungi, usually have positive effects. Recent research revealed that belowground interactions between plants and functionally distinct groups of microorganisms cascade up to aboveground plant associates such as herbivores and their natural enemies. However, while functionally distinct belowground microorganisms commonly co-occur in the rhizosphere, their combined effects, and relative contributions, respectively, on performance of aboveground plant-associated organisms are virtually unexplored. Here, we scrutinized and disentangled the effects of free living nitrogen-fixing (diazotrophic) bacteria Azotobacter chroococcum (DB) and arbuscular mycorrhizal fungi Glomus mosseae (AMF) on host plant choice and reproduction of the herbivorous two-spotted spider mite Tetranychus urticae on common bean plants Phaseolus vulgaris. Additionally, we assessed plant growth, and AMF and DB occurrence and density as affected by each other. Both AMF alone and DB alone increased spider mite reproduction to similar levels, as compared to the control, and exerted additive effects under co-occurrence. These effects were similarly apparent in host plant choice, that is, the mites preferred leaves from plants with both AMF and DB to plants with AMF or DB to plants grown without AMF and DB. DB, which also act as AMF helper bacteria, enhanced root colonization by AMF, whereas AMF did not affect DB abundance. AMF but not DB increased growth of reproductive plant tissue and seed production, respectively. Both AMF and DB increased the biomass of vegetative aboveground plant tissue. Our study breaks new ground in multitrophic belowground-aboveground research by providing first insights into the fitness implications of plant-mediated interactions between interrelated belowground fungi-bacteria and aboveground herbivores. PMID- 26380702 TI - Potential merger of ancient lineages in a passerine bird discovered based on evidence from host-specific ectoparasites. AB - The merger of formerly isolated lineages is hypothesized to occur in vertebrates under certain conditions. However, despite many demonstrated instances of introgression between taxa in secondary contact, examples of lineage mergers are rare. Preliminary mtDNA sequencing of a Malagasy passerine, Xanthomixis zosterops (Passeriformes: Bernieridae), indicated a possible instance of merging lineages. We tested the hypothesis that X. zosterops lineages are merging by comparing mtDNA sequence and microsatellite data, as well as mtDNA sequence data from host specific feather lice in the genus Myrsidea (Phthiraptera: Menoponidae). Xanthomixis zosterops comprises four deeply divergent, broadly sympatric, cryptic mtDNA clades that likely began diverging approximately 3.6 million years ago. Despite this level of divergence, the microsatellite data indicate that the X. zosterops mtDNA clades are virtually panmictic. Three major phylogroups of Myrsidea were found, supporting previous allopatry of the X. zosterops clades. In combination, the datasets from X. zosterops and its Myrsidea document a potential merger of previously allopatric lineages that likely date to the Pliocene. This represents the first report of sympatric apparent hybridization among more than two terrestrial vertebrate lineages. Further, the mtDNA phylogeographic pattern of X. zosterops, namely the syntopy of more than two deeply divergent cryptic clades, appears to be a novel scenario among vertebrates. We highlight the value of gathering multiple types of data in phylogeographic studies to contribute to the study of vertebrate speciation. PMID- 26380704 TI - Effects of spatial scale of sampling on food web structure. AB - This study asks whether the spatial scale of sampling alters structural properties of food webs and whether any differences are attributable to changes in species richness and connectance with scale. Understanding how different aspects of sampling effort affect ecological network structure is important for both fundamental ecological knowledge and the application of network analysis in conservation and management. Using a highly resolved food web for the marine intertidal ecosystem of the Sanak Archipelago in the Eastern Aleutian Islands, Alaska, we assess how commonly studied properties of network structure differ for 281 versions of the food web sampled at five levels of spatial scale representing six orders of magnitude in area spread across the archipelago. Species (S) and link (L) richness both increased by approximately one order of magnitude across the five spatial scales. Links per species (L/S) more than doubled, while connectance (C) decreased by approximately two-thirds. Fourteen commonly studied properties of network structure varied systematically with spatial scale of sampling, some increasing and others decreasing. While ecological network properties varied systematically with sampling extent, analyses using the niche model and a power-law scaling relationship indicate that for many properties, this apparent sensitivity is attributable to the increasing S and decreasing C of webs with increasing spatial scale. As long as effects of S and C are accounted for, areal sampling bias does not have a special impact on our understanding of many aspects of network structure. However, attention does need be paid to some properties such as the fraction of species in loops, which increases more than expected with greater spatial scales of sampling. PMID- 26380705 TI - Maintenance of brucellosis in Yellowstone bison: linking seasonal food resources, host-pathogen interaction, and life-history trade-offs. AB - The seasonal availability of food resources is an important factor shaping the life-history strategies of organisms. During times of nutritional restriction, physiological trade-offs can induce periods of immune suppression, thereby increasing susceptibility to infectious disease. Our goal was to provide a conceptual framework describing how the endemic level bovine brucellosis (Brucella abortus) may be maintained in Yellowstone bison based on the seasonality of food resources and the life-history strategies of the host and pathogen. Our analysis was based on active B. abortus infection (measured via bacterial culture), nutritional indicators (measured as metabolites and hormones in plasma), and carcass measurements of 402 slaughtered bison. Data from Yellowstone bison were used to investigate (1) whether seasonal changes in diet quality affect nutritional condition and coincide with the reproductive needs of female bison; (2) whether active B. abortus infection and infection intensities vary with host nutrition and nutritional condition; and (3) the evidence for seasonal changes in immune responses, which may offer protection against B. abortus, in relation to nutritional condition. Female bison experienced a decline in nutritional condition during winter as reproductive demands of late gestation increased while forage quality and availability declined. Active B. abortus infection was negatively associated with bison age and nutritional condition, with the intensity of infection negatively associated with indicators of nutrition (e.g., dietary protein and energy) and body weight. Data suggest that protective cell-mediated immune responses may be reduced during the B. abortus transmission period, which coincides with nutritional insufficiencies and elevated reproductive demands during spring. Our results illustrate how seasonal food restriction can drive physiological trade-offs that suppress immune function and create infection and transmission opportunities for pathogens. PMID- 26380706 TI - Mining from transcriptomes: 315 single-copy orthologous genes concatenated for the phylogenetic analyses of Orchidaceae. AB - Phylogenetic relationships are hotspots for orchid studies with controversial standpoints. Traditionally, the phylogenies of orchids are based on morphology and subjective factors. Although more reliable than classic phylogenic analyses, the current methods are based on a few gene markers and PCR amplification, which are labor intensive and cannot identify the placement of some species with degenerated plastid genomes. Therefore, a more efficient, labor-saving and reliable method is needed for phylogenic analysis. Here, we present a method of orchid phylogeny construction using transcriptomes. Ten representative species covering five subfamilies of Orchidaceae were selected, and 315 single-copy orthologous genes extracted from the transcriptomes of these organisms were applied to reconstruct a more robust phylogeny of orchids. This approach provided a rapid and reliable method of phylogeny construction for Orchidaceae, one of the most diversified family of angiosperms. We also showed the rigorous systematic position of holomycotrophic species, which has previously been difficult to determine because of the degenerated plastid genome. We concluded that the method presented in this study is more efficient and reliable than methods based on a few gene markers for phylogenic analyses, especially for the holomycotrophic species or those whose DNA sequences have been difficult to amplify. Meanwhile, a total of 315 single-copy orthologous genes of orchids are offered and more informative loci could be used in the future orchid phylogenetic studies. PMID- 26380707 TI - Large-scale spatial variation in feather corticosterone in invasive house sparrows (Passer domesticus) in Mexico is related to climate. AB - Ecologists frequently use physiological tools to understand how organisms cope with their surroundings but rarely at macroecological scales. This study describes spatial variation in corticosterone (CORT) levels in feathers of invasive house sparrows (Passer domesticus) across their range in Mexico and evaluates CORT-climate relationships with a focus on temperature and precipitation. Samples were collected from 49 sites across Mexico. Feather CORT (CORTf) was measured using methanol-based extraction and radioimmunoassay. Relationships between CORTf and spatial and climate variables were examined using simple linear regressions. Ordination was used on climate data, CORTf was plotted against the resulting axes, and univariate regression trees were used to identify important predictors of CORTf. Universal kriging interpolation was used to illustrate spatial variation in CORTf across Mexico. Correlations with ordination axes showed that high CORTf was associated with low precipitation during the rainy season and low dry season temperatures. Specifically, CORTf was negatively related to May precipitation and January and July minimum temperatures, and positively related to April deuterium excess and June minimum temperatures. CORTf was higher in second-year birds compared to after-hatch years and after-second years. House sparrows had higher CORTf levels in the hot, dry, north-central region of Mexico, and CORTf was negatively related to temperature and precipitation. House sparrows molt primarily from August-September but climate conditions throughout the year were important predictors of CORTf, suggesting that conditions outside of molt can carry over to influence energetics during feather growth. These data suggest that dry conditions are challenging for house sparrows in Mexico, supporting previous work showing that precipitation is an important predictor of broad-scale CORT variation. This work highlights the utility of CORTf for evaluating the influence of physiology on current avian range limits; furthermore, these data may allow us to predict future changes in species distributions. PMID- 26380708 TI - Role of phenotypic plasticity and population differentiation in adaptation to novel environmental conditions. AB - Species can adapt to new environmental conditions either through individual phenotypic plasticity, intraspecific genetic differentiation in adaptive traits, or both. Wild emmer wheat, Triticum dicoccoides, an annual grass with major distribution in Eastern Mediterranean region, is predicted to experience in the near future, as a result of global climate change, conditions more arid than in any part of the current species distribution. To understand the role of the above two means of adaptation, and the effect of population range position, we analyzed reaction norms, extent of plasticity, and phenotypic selection across two experimental environments of high and low water availability in two core and two peripheral populations of this species. We studied 12 quantitative traits, but focused primarily on the onset of reproduction and maternal investment, which are traits that are closely related to fitness and presumably involved in local adaptation in the studied species. We hypothesized that the population showing superior performance under novel environmental conditions will either be genetically differentiated in quantitative traits or exhibit higher phenotypic plasticity than the less successful populations. We found the core population K to be the most plastic in all three trait categories (phenology, reproductive traits, and fitness) and most successful among populations studied, in both experimental environments; at the same time, the core K population was clearly genetically differentiated from the two edge populations. Our results suggest that (1) two means of successful adaptation to new environmental conditions, phenotypic plasticity and adaptive genetic differentiation, are not mutually exclusive ways of achieving high adaptive ability; and (2) colonists from some core populations can be more successful in establishing beyond the current species range than colonists from the range extreme periphery with conditions seemingly closest to those in the new environment. PMID- 26380709 TI - Fuel moisture content enhances nonadditive effects of plant mixtures on flammability and fire behavior. AB - Fire behavior of plant mixtures includes a complex set of processes for which the interactive contributions of its drivers, such as plant identity and moisture, have not yet been unraveled fully. Plant flammability parameters of species mixtures can show substantial deviations of fire properties from those expected based on the component species when burnt alone; that is, there are nonadditive mixture effects. Here, we investigated how fuel moisture content affects nonadditive effects in fire behavior. We hypothesized that both the magnitude and variance of nonadditivity in flammability parameters are greater in moist than in dry fuel beds. We conducted a series of experimental burns in monocultures and 2 species mixtures with two ericaceous dwarf shrubs and two bryophyte species from temperate fire-prone heathlands. For a set of fire behavior parameters, we found that magnitude and variability of nonadditive effects are, on average, respectively 5.8 and 1.8 times larger in moist (30% MC) species mixtures compared to dry (10% MC) mixed fuel beds. In general, the moist mixtures caused negative nonadditive effects, but due to the larger variability these mixtures occasionally caused large positive nonadditive effects, while this did not occur in dry mixtures. Thus, at moister conditions, mixtures occasionally pass the moisture threshold for ignition and fire spread, which the monospecific fuel beds are unable to pass. We also show that the magnitude of nonadditivity is highly species dependent. Thus, contrary to common belief, the strong nonadditive effects in mixtures can cause higher fire occurrence at moister conditions. This new integration of surface fuel moisture and species interactions will help us to better understand fire behavior in the complexity of natural ecosystems. PMID- 26380710 TI - Exposing the structure of an Arctic food web. AB - How food webs are structured has major implications for their stability and dynamics. While poorly studied to date, arctic food webs are commonly assumed to be simple in structure, with few links per species. If this is the case, then different parts of the web may be weakly connected to each other, with populations and species united by only a low number of links. We provide the first highly resolved description of trophic link structure for a large part of a high-arctic food web. For this purpose, we apply a combination of recent techniques to describing the links between three predator guilds (insectivorous birds, spiders, and lepidopteran parasitoids) and their two dominant prey orders (Diptera and Lepidoptera). The resultant web shows a dense link structure and no compartmentalization or modularity across the three predator guilds. Thus, both individual predators and predator guilds tap heavily into the prey community of each other, offering versatile scope for indirect interactions across different parts of the web. The current description of a first but single arctic web may serve as a benchmark toward which to gauge future webs resolved by similar techniques. Targeting an unusual breadth of predator guilds, and relying on techniques with a high resolution, it suggests that species in this web are closely connected. Thus, our findings call for similar explorations of link structure across multiple guilds in both arctic and other webs. From an applied perspective, our description of an arctic web suggests new avenues for understanding how arctic food webs are built and function and of how they respond to current climate change. It suggests that to comprehend the community-level consequences of rapid arctic warming, we should turn from analyses of populations, population pairs, and isolated predator-prey interactions to considering the full set of interacting species. PMID- 26380711 TI - Step by step: reconstruction of terrestrial animal movement paths by dead reckoning. AB - BACKGROUND: Research on wild animal ecology is increasingly employing GPS telemetry in order to determine animal movement. However, GPS systems record position intermittently, providing no information on latent position or track tortuosity. High frequency GPS have high power requirements, which necessitates large batteries (often effectively precluding their use on small animals) or reduced deployment duration. Dead-reckoning is an alternative approach which has the potential to 'fill in the gaps' between less resolute forms of telemetry without incurring the power costs. However, although this method has been used in aquatic environments, no explicit demonstration of terrestrial dead-reckoning has been presented. RESULTS: We perform a simple validation experiment to assess the rate of error accumulation in terrestrial dead-reckoning. In addition, examples of successful implementation of dead-reckoning are given using data from the domestic dog Canus lupus, horse Equus ferus, cow Bos taurus and wild badger Meles meles. CONCLUSIONS: This study documents how terrestrial dead-reckoning can be undertaken, describing derivation of heading from tri-axial accelerometer and tri axial magnetometer data, correction for hard and soft iron distortions on the magnetometer output, and presenting a novel correction procedure to marry dead reckoned paths to ground-truthed positions. This study is the first explicit demonstration of terrestrial dead-reckoning, which provides a workable method of deriving the paths of animals on a step-by-step scale. The wider implications of this method for the understanding of animal movement ecology are discussed. PMID- 26380712 TI - In search of rules behind environmental framing; the case of head pitch. AB - BACKGROUND: Whether, and how, animals move requires them to assess their environment to determine the most appropriate action and trajectory, although the precise way the environment is scanned has been little studied. We hypothesized that head attitude, which effectively frames the environment for the eyes, and the way it changes over time, would be modulated by the environment. METHOD: To test this, we used a head-mounted device (Human-Interfaced Personal Observation platform - HIPOP) on people moving through three different environments; a botanical garden ('green' space), a reef ('blue' space), and a featureless corridor, to examine if head movement in the vertical axis differed between environments. Template matching was used to identify and quantify distinct behaviours. CONCLUSIONS: The data on head pitch from all subjects and environments over time showed essentially continuous clear waveforms with varying amplitude and wavelength. There were three stylised behaviours consisting of smooth, regular peaks and troughs in head pitch angle and variable length fixations during which the head pitch remained constant. These three behaviours accounted for ca. 40 % of the total time, with irregular head pitch changes accounting for the rest. There were differences in rates of manifestation of behaviour according to environment as well as environmentally different head pitch values of peaks, troughs and fixations. Finally, although there was considerable variation in head pitch angles, the peak and trough values bounded most of the variation in the fixation pitch values. It is suggested that the constant waveforms in head pitch serve to inform people about their environment, providing a scanning mechanism. Particular emphasis to certain sectors is manifest within the peak and trough limits and these appear modulated by the distribution of the points where fixation, interpreted as being due to objects of interest, occurs. This behaviour explains how animals allocate processing resources to the environment and shows promise for movement studies attempting to elucidate which parts of the environment affect movement trajectories. PMID- 26380713 TI - Circadian behaviour of Tectus (Trochus) niloticus in the southwest Pacific inferred from accelerometry. AB - BACKGROUND: Behaviour and time spent active and inactive are key factors in animal ecology, with important consequences for bioenergetics. For the first time, here, we equipped the gastropod Tectus (= Trochus) niloticus with accelerometers to describe activity rhythms at two sites in the Southwest Pacific with different temperature regimes: New Caledonia and Vanuatu. RESULTS: Based on a 24-hour cycle, T. niloticus activity began at dusk and gradually stopped during the night, before sunrise. This nocturnal behaviour was characterised by short (duration <30 s), low intensity (acceleration < 0.12 g) movements and was probably associated with foraging behaviour. We assumed that activity ceased once the animal was satiated. Our analysis of two size groups in Vanuatu (80-90 mm vs. 120-140 mm, basal shell diameter) revealed a size effect; smaller specimens displayed greater activity, reflected by more intense and longer movements while migrating at night toward the edge of the reef. This nocturnal behaviour is not uncommon for grazing gastropods and is mainly associated with attempting to avoid visual predators whilst feeding. CONCLUSIONS: The use of accelerometers coupled with light and temperature sensors provided detailed information on topshell behaviour and physiology under natural conditions. These data provide a foundation for identifying potential changes in the fine-scale behaviour of T. niloticus in response to environmental changes, which is essential in animal ecology and stock conservation. PMID- 26380714 TI - Early detection of extended-spectrum beta-lactamase from blood culture positive for an Enterobacteriaceae using betaLACTA test. AB - Bacterial pellets from Enterobacteriaceae positive blood cultures prepared using ammonium chloride were tested for rapid detection of beta-lactamase using the commercial betaLACTA test and read after 30 minutes. During 7 months, 137 bacterial pellets were tested prospectively. betaLACTA test exhibited a sensitivity of 75% and a specificity of 100% for the detection of third generation cephalosporin resistance. False negative tests were mainly observed with hyperproduced chromosomal or plasmid-borne AmpC. PMID- 26380715 TI - Early and sustained blood pressure control is necessary for stroke prevention. PMID- 26380716 TI - Video-assisted thoracoscopic lobectomy versus stereotactic radiotherapy for stage I lung cancer. PMID- 26380717 TI - Improve survival from prolonged mechanical ventilation: beginning with first step. PMID- 26380718 TI - A new free-cost e-service supporting clinicians to manage their difficult-to treat TB cases: the ERS-WHO TB consilium. PMID- 26380719 TI - Full or hypocaloric nutritional support for the critically ill patient: is less really more? PMID- 26380565 TI - Search for Higgs boson pair production in the [Formula: see text] final state from pp collisions at [Formula: see text] TeVwith the ATLAS detector. AB - A search for Higgs boson pair production [Formula: see text] is performed with 19.5 fb[Formula: see text] of proton-proton collision data at [Formula: see text] TeV, which were recorded by the ATLAS detector at the Large Hadron Collider in 2012. The decay products of each Higgs boson are reconstructed as a high-momentum [Formula: see text] system with either a pair of small-radius jets or a single large-radius jet, the latter exploiting jet substructure techniques and associated b-tagged track-jets. No evidence for resonant or non-resonant Higgs boson pair production is observed. The data are interpreted in the context of the Randall-Sundrum model with a warped extra dimension as well as the two-Higgs doublet model. An upper limit on the cross-section for [Formula: see text] of 3.2 (2.3) fb is set for a Kaluza-Klein graviton [Formula: see text] mass of 1.0 (1.5) TeV, at the 95 % confidence level. The search for non-resonant Standard Model hh production sets an observed 95 % confidence level upper limit on the production cross-section [Formula: see text] of 202 fb, compared to a Standard Model prediction of [Formula: see text] fb. PMID- 26380720 TI - Noninvasive respiratory support for acute respiratory failure-high flow nasal cannula oxygen or non-invasive ventilation? PMID- 26380721 TI - Magnetic resonance imaging for staging of non-small-cell lung cancer-technical advances and unmet needs. PMID- 26380722 TI - Management of subsolid pulmonary nodules in CT lung cancer screening. AB - The distinct appearance and behavior of subsolid pulmonary nodules (SSNs) has resulted in separate recommendations for the management of solitary SSNs, both for incidentally detected as well as for screen detected nodules. However, these guidelines have been based primarily on expert opinion. Recently two studies were published regarding SSNs detected in low-dose computed tomography (LDCT) lung cancer screening, including management advices. PMID- 26380724 TI - Illuminating anthracycline cardiotoxicity: the renaissance of evidence-based onco cardiology. PMID- 26380723 TI - The impact of percutaneous coronary intervention of chronic total occlusions on left ventricular function and clinical outcomes. AB - A meta-analysis by Hoebers et al. reported that successful chronic total occlusion (CTO) recanalization resulted in an increase in left ventricular (LV) ejection fraction by 4.44% (P<0.01) and a reduction in LV end-diastolic volume by 6.14 mL/m(2) during follow-up as compared with baseline, suggesting beneficial LV remodeling. These findings are important as the myocardium supplied by a CTO frequently has sustained irreversible injury and further support the clinical benefits of CTO interventions. PMID- 26380725 TI - The role of SOX-2 on the survival of patients with non-small cell lung cancer. AB - BACKGROUND: Lung cancer is the most commonly diagnosed cancer as well as the leading cause of cancer death worldwide. Observational studies on the prognostic role of SOX-2 in non-small-cell lung cancer (NSCLC) are controversial. METHODS: To clarify the impact of SOX-2 in NSCLC survival, we performed this meta-analysis that included eligible studies. The combined hazard ratios and their corresponding 95% confidence intervals (95% CI) were calculated in terms of overall survival. RESULTS: A total of seven studies with 1,944 patients were evaluable for this meta-analysis. The studies were categorized by histology, disease stage and patient race. Our results suggested that SOX-2 overexpression had a favorable impact on survival of patients with NSCLC, the HR (95% CI) was 0.57 (0.48 to 0.65). However, highly significant heterogeneity was detected among these studies (I(2)=76.7%, P=0.000). CONCLUSIONS: SOX-2 overexpression indicates a favorable prognosis for patients with NSCLC. PMID- 26380726 TI - A chest drainage system with a real-time pressure monitoring device. AB - BACKGROUND: Tube thoracostomy is a common procedure. A chest bottle may be used to both collect fluids and monitor the recovery of the chest condition. The presence of the "tidaling phenomenon" in the bottle can be reflective of the extent of patient's recovery. OBJECTIVES: However, current practice essentially depends on gross observation of the bottle. The device used here is designed for a real-time monitoring of change in pleural pressure to allow clinicians to objectively determine when the lung has recovered, which is crucially important in order to judge when to remove the chest tube. METHODS: The device is made of a pressure sensor with an operating range between -100 to +100 cmH2O and an amplifying using the "Wheatstone bridge" concept. Recording and analysis was performed with LABview software. The data can be shown in real-time on screen and also be checked retrospectively. The device was connected to the second part of a three-bottle drain system by a three-way connector. RESULTS: The test animals were two 40-kg pigs. We used a thoracoscopic procedure to create an artificial lung laceration with endoscopic scissors. Active air leaks could result in vigorous tidaling phenomenon up to 20 cmH2O. In the absence of gross tidaling phenomenon, the pressure changes were around 0.25 cmH2O. CONCLUSIONS: This real time pleural pressure monitoring device can help clinicians objectively judge the extent of recovery of the chest condition. It can be used as an effective adjunct with the current chest drain system. PMID- 26380727 TI - EPHX1 rs2234922 polymorphism and lung cancer susceptibility in Asian populations: a meta-analysis. AB - OBJECTIVE: Polymorphisms of epoxide hydrolase 1 (EPHX1) rs2234922 have been reported to be associated with variations in EPHX1 activity. Many studies have investigated the association between EPHX1 rs2234922 polymorphism and lung cancer risk, but their results have been inconsistent. The purpose of this study was to perform a meta-analysis of all eligible studies to derive a more precise estimation of the associations of EPHX1 rs2234922 polymorphism with lung cancer. METHODS: The PubMed was searched for case-control studies published up to Oct 01, 2014. Data were extracted and pooled odds ratios (ORs) with 95% confidence interval (CI) were calculated. The pooled ORs for the risk associated with the genotypes of homozygote G/G and G allele carriers (A/G + G/G) with the A/A genotype were calculated. Heterogeneity assumption was checked by the chi-square based Q-test. A P value greater than 0.10 for the Q-test indicates a lack of heterogeneity among studies, so the pooled OR estimate of the each study was calculated by the fixed-effects model (the Mantel-Haenszel method). Otherwise, the random-effects model (the DerSimonian and Laird method) was used. RESULTS: In this meta-analysis, we assessed eight published studies involving comprising 1,175 cases and 1,550 controls of the association between EPHX1 rs2234922 polymorphism and lung cancer risk. For the homozygote G/G and G allele carriers (A/G + G/G), the pooled ORs were 1.47 (95% CI: 1.18-1.79, P=0.007 for heterogeneity) and 1.36 (95% CI: 1.14-1.62, P=0.828 for heterogeneity), when compared with the homozygous wild-type genotype (A/A). CONCLUSIONS: EPHX1 rs2234922 polymorphism contributes to risk of lung cancer among Asian population. PMID- 26380728 TI - A modified nebulization modality versus classical ultrasonic nebulization and oxygen-driven nebulization in facilitating airway clearance in patients with acute exacerbation of chronic obstructive pulmonary disease: a randomized controlled trial. AB - BACKGROUND: Ultrasonic nebulization (UN) and oxygen-driven nebulization (ON), two commonly used modalities for nebulization inhalation, are not ideally suitable for patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). METHODS: A total of 91 patients with AECOPD were randomized to three groups given different nebulization modalities: ON, UN, and ultrasonic nebulization with warming and oxygen (UNWO). The sputum clearance, lung function, changes in physiological measures such as peripheral oxygen saturation (SpO2) and tolerance to these nebulization modalities were recorded and compared among the three groups. RESULTS: The time to the first expectoration was shorter and the sputum volume was larger after UN and UNWO than after ON (both P<0.01). Compared with pre-nebulization, SpO2 significantly increased (P<0.01) and the dyspnea decreased significantly (P<0.05) after UNWO. The SpO2 and dyspnea post-UNWO were significantly better than those post-UN (P<0.01, P<0.05), but not statistically different from those post-ON (both P>0.05). UNWO demonstrated significantly greater comfort and longer duration of nebulization than UN (P<0.01, P<0.05), but no significant differences in these respects from ON (both P>0.05). Forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and peak expiratory flow (PEF) decreased significantly after UNWO (P<0.05, P<0.01, and P<0.01, respectively). CONCLUSIONS: UNWO may promote expectoration of sputum with fewer adverse reactions and a higher level of comfort than simple UN and ON. Therefore, it can be used as an adjuvant therapy for AECOPD patients. PMID- 26380729 TI - Predictors of dynamic hyperinflation during the 6-minute walk test in stable chronic obstructive pulmonary disease patients. AB - BACKGROUND: Dynamic hyperinflation (DH) is a major contributor to exercise limitation in chronic obstructive pulmonary disease (COPD). Therefore, we aimed to elucidate the physiological factors responsible for DH development during the 6-minute walk test (6MWT) in COPD patients and compare ventilatory response to the 6MWT in hyperinflators and non-hyperinflators. METHODS: A total of 105 consecutive subjects with stable COPD underwent a 6MWT, and the Borg dyspnea scale, oxygen saturation (SpO2), breathing pattern, and inspiratory capacity (IC) were recorded before and immediately after walking. The change in IC was measured, and subjects were divided into hyperinflators (DeltaIC >0.0 L) and non hyperinflators (DeltaIC <=0.0 L). Spirometry, the Modified Medical Research Council (MMRC) dyspnea scale and St George's Respiratory Questionnaire (SGRQ) were also assessed. RESULTS: DH was present in 66.67% of subjects. DeltaIC/IC was significantly and negatively correlated with the small airway function. On multiple stepwise regression analysis forced expiratory flow after exhaling 50% of the forced vital capacity (FEF50%) was the only predictor of DeltaIC/IC. Non hyperinflators had a higher post-walking VT (t=2.419, P=0.017) and post-walking VE (t=2.599, P=0.011) than the hyperinflators did. Age and resting IC were independent predictors of the 6-minute walk distance (6MWD) in hyperinflators. CONCLUSIONS: DH was considerably common in subjects with COPD. Small airway function may partly contribute to the DH severity during walking. The ventilator response to the 6MWT differed between hyperinflators and non-hyperinflators. Resting hyperinflation is an important predictor of functional exercise capacity in hyperinflators. PMID- 26380730 TI - Human embryonic lung fibroblasts treated with artesunate exhibit reduced rates of proliferation and human cytomegalovirus infection in vitro. AB - BACKGROUND: Cytomegalovirus (CMV) pneumonia is a major cause of death in immunosuppressed patients. Despite the effective treatment with ganciclovir (GCV) and other antiviral agents, the mortality rate remains between 30% to 50%. Recently, the anti-malarial drug artesunate (ART) wasfound to exhibit significant anti-viral activity. Here, we examined the effects of ART on human cytomegalovirus (HCMV) infection and human embryonic lung fibroblast (HELF) proliferation in vitro. METHODS: HELFs infected with the GFP-expressing Towne-BAC strain of HCMV were divided into three treatment groups: Group I, cells treated with ART for 1.5 h before HCMV inoculation; Group II, cells infected with HCMV that was pre-treated with ART for 1.5 h before HCMV inoculation; Group III, cells that were treated with ART at 1.5 h post-HCMV inoculation. GFP expression was observed daily by fluorescence microscopy, and the number of GFP-positive cells in each experimental group was recorded at 4-5 days post-infection. At 10 days post-infection, the viability of cells in each group was recorded. GCV treatment was used as a control. RESULTS: While no significant effects on cytotoxicity, cell viability, viral infection rates, or antiviral activity were observed upon treatment of Group I or II cells with GCV or low levels of ART, the ART-treated Group III population exhibited significantly reduced rates of infection at drug concentrations higher than 12.5 uM. Similarly, we observed a GCV concentration dependent reduction in the viral infection rate in Group III cells. Notably, ART treated, but not GCV-treated, cells also exhibited decreased proliferation. The 50% cytostatic concentrations (CC50) and the half maximal inhibitory concentrations (IC50) of ART and GCV were 54.382 uM and 12.679 uM, and 3.76 M and 14.479 uM, respectively. CONCLUSIONS: In addition to its robust antiviral activity, ART inhibits proliferation of HCMV-infected lung fibroblasts, making it a potential next-generation drug for CMV pneumonia treatment and for reducing fibroproliferation and fibrosis in these patients. PMID- 26380731 TI - Low molecular weight heparin once versus twice for thromboprophylaxis following esophagectomy: a randomised, double-blind and placebo-controlled trial. AB - BACKGROUND: Venous thromboembolism (VTE) remained common complication following surgical resection of esophageal cancer. In this prospective randomized double blind placebo-controlled trial (NCT01267305), we aim to compare the safety and efficacy between low molecular weight heparin (LMWH) once-daily (QD) and twice daily (BID) for the prophylaxis of VTE following esophagectomy. METHODS: During August 2012 to July 2013, patients underwent esophagectomy were randomly assigned to nadroparin calcium QD (4,100 AxaIU qd + placebo qd, group QD), or nadroparin calcium BID (4,100 AxaIU q12h, group BID) in the prophylaxis of VTE. All patients received thrombelastography (TEG) before and 0/24/48/72 hours after operation. Daily vascular ultrasound of lower extremities was followed during the first 7 postoperative days to confirm the suspected deep venous thrombosis (DVT). Cumulatively postoperative chest drainage at 72 hours after the surgery was collected to identify the difference in volume and red blood cell (RBC) counts between the two groups. Any bleeding events and thromboembolic events were also documented. RESULTS: A total of 117 patients were enrolled in this study, and 111 eligible patients were randomly assigned (group QD: 55 patients; group BID: 56 patients). Patients' clinical features were close between the two groups. TEG analysis [R time, K time, alpha angel and maximum amplitude (MA)] before and instantly after operation showed nearly identical results. However, compared with group QD, all TEG measurements of 24/48/72 hours postoperatively showed significantly prolonged R time and K time, and decreased alpha angel in group BID. In ultrasound follow-ups, a total of four cases of DVT (four cases in group QD and no case in group BID) were found in this cohort (7.27% versus 0%, P=0.046), and one case of pulmonary embolism (PE) (in group QD) was observed. The incidence of VTE was lower in group BID (9.09% versus 0%, P=0.032). At 72 hours after surgery, the cumulative volume of chest drainage were close between these two groups (1,001.39+/-424.58 versus 1,133.61+/-513.93 mL, P=0.406). RBC counts in chest drainage were also identical between two groups [(2.56+/-1.98)*10(5) versus (2.71+/-4.67)*10(5), P=0.61]. No patient died due to VTE or bleeding events. CONCLUSIONS: For the prophylaxis of VTE, BID LMWH provided more potent efficacy and equal safety when compared to QD LMWH in patients undergoing selective esophagectomy. Further study based on larger population is required to confirm these findings. PMID- 26380732 TI - Midterm results of "treat and repair" for adults with non-restrictive ventricular septal defect and severe pulmonary hypertension. AB - BACKGROUND: A non-restrictive ventricular septal defect (VSD) can cause intracardiac left to right shunt, which leads to increased pulmonary vascular resistance (PVR) and pulmonary hypertension causes bi-directional or even right left shunt, namely the Eisenmenger's syndrome. For patients with non-restrictive VSD with severe pulmonary hypertension at stage of near or to be Eisenmenger's syndrome, traditional VSD repair carries high mortality and poor prognosis. Recently, targeted drug therapy was used to decrease pulmonary circulation resistance in these patients before they receive defect repair surgery, namely "treat and repair" strategy, however, there is few reports about the midterm result of this strategy in adults with non-restrictive VSD with severe pulmonary hypertension at stage of near or to be Eisenmenger's syndrome. METHODS: In this study, we used this strategy to treat 41 adult VSD patients who received bosentan as the targeted therapy to decrease their PVR before and after repair surgery. RESULTS: A total of 39 patients were followed up for an average of 37 months. None of the patients died during follow-up. Among them, 36 cases continued targeted drug therapy, whose mean pulmonary artery pressure (mPAP) was significantly reduced, including 31 cases with mPAP <50 mmHg, and the valve of tap hole was closed. Besides, the SpO2 was significantly elevated. CONCLUSIONS: These results demonstrated that "treat-and-repair" strategy may be a viable approach for the adults with non-restrictive VSD with severe pulmonary hypertension at stage of near or to be Eisenmenger's syndrome. PMID- 26380733 TI - Major morbidity after video-assisted thoracic surgery lung resections: a comparison between the European Society of Thoracic Surgeons definition and the Thoracic Morbidity and Mortality system. AB - BACKGROUND: The thoracic morbidity and mortality (TM&M) classification system univocally encodes the postoperative adverse events by their management complexity. This study aims to compare the distribution of the severity of complications according to the TM&M system versus the distribution according to the classification proposed by European Society of Thoracic Surgeons (ESTS) Database in a population of patients submitted to video assisted thoracoscopic surgery (VATS) lung resection. METHODS: A total of 227 consecutive patients submitted to VATS lobectomy for lung cancer were analyzed. Any complication developed postoperatively was graded from I to V according to the TM&M system, reflecting the increasing severity of its management. We verified the distribution of the different grades of complications and analyzed their frequency among those defined as "major cardiopulmonary complications" by the ESTS Database. RESULTS: Following the ESTS definitions, 20 were the major cardiopulmonary complications [atrial fibrillation (AF): 10, 50%; adult respiratory distress syndrome (ARDS): 1, 5%; pulmonary embolism: 2, 10%; mechanical ventilation >24 h: 1, 5%; pneumonia: 3, 15%; myocardial infarct: 1, 5%; atelectasis requiring bronchoscopy: 2, 10%] of which 9 (45%) were reclassified as minor complications (grade II) by the TM&M classification system. According to the TM&M system, 10/34 (29.4%) of all complications were considered minor (grade I or II) while 21/34 (71.4%) as major (IIIa: 8, 23.5%; IIIb: 4, 11.7%; IVa: 8, 23.5%; IVb: 1, 2.9%; V: 3, 8.8%). Other 14 surgical complications occurred and were classified as major complications according to the TM&M system. CONCLUSIONS: The distribution of postoperative complications differs between the two classification systems. The TM&M grading system questions the traditional classification of major complications following VATS lung resection and may be used as an additional endpoint for outcome analyses. PMID- 26380734 TI - Clinical efficacy of crizotinib in Chinese patients with ALK-positive non-small cell lung cancer with brain metastases. AB - BACKGROUND: Crizotinib has been associated with intracranial disease control in anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC) patients with brain metastases. Continued crizotinib treatment has also been used for prolonged disease control in patients experiencing isolated central nervous system (CNS) failure. However, there are few studies of crizotinib efficacy in ALK-positive Chinese patients. Thus, we retrospectively investigated the clinical efficacy of crizotinib in Chinese ALK-positive NSCLC patients with brain metastases at baseline, and evaluated the clinical benefit of continuing crizotinib beyond CNS failure. METHODS: A total of 120 advanced ALK-positive NSCLC patients treated with crizotinib were enrolled with 38 having brain metastases at baseline. The objective response rate (ORR) and progression-free survival (PFS) were compared between patients with and without brain metastases at baseline. A subset of patients who developed CNS failure continued crizotinib treatment beyond progressive disease (PD), and the second PFS from the time of the first progression was also evaluated. RESULTS: The ORR of crizotinib was similar between patients with and without brain metastases at baseline (68.4% vs. 69.5%, P=0.904). However, the patients without brain metastases at baseline experienced a longer median PFS [10.0 months, 95% confidence interval (CI), 7.6 12.5 vs. 7.0 months, 95% CI, 6.4-7.6; P=0.021]. Among 88 patients with PD defined Response Evaluation Criteria in Solid Tumors (RECIST), 33 developed CNS failure. A total of 24 patients who developed CNS failure continued crizotinib treatment beyond PD, and they achieved a second median PFS of 6.3 months (95% CI, 2.9-9.7). CONCLUSIONS: Chinese ALK-positive NSCLC patients with brain metastases achieved a similar response to crizotinib and significantly shorter PFS compared to those without brain metastases at baseline. Continuous administration of crizotinib beyond PD in patients developing CNS failure appeared to be a valid treatment strategy. PMID- 26380735 TI - Clarithromycin might attenuate the airway inflammation of smoke-exposed asthmatic mice via affecting HDAC2. AB - BACKGROUND: Smoke has been proved to be one of the most dangerous ingredients leading to the unsatisfying treatment response of asthmatics to inhaled corticosteroids (ICS) therapy. Macrolides, a class of antibiotics, possess the traits of immunomodulation and anti-inflammation besides antimicrobial activity. Given that studies on the efficacy of macrolides on the refractory asthma patient have diverting conclusions, this article was carried on to investigate the effects of macrolide on the airway inflammation of smoke-exposed asthmatic mice. METHODS: BALB/c mice were chosen to be the subjects of this study. They were raised to establish asthma model (OVA group); and one asthma group were exposed to the smoke (SEA group), one asthma group were treat with clarithromycin (CAM group) after smoke exposure. Control group mice were used as parallel comparison. Total inspiratory resistance (RL), expiratory resistance of the lung (Re) and lung compliance (Cdyn) were the main index to evaluate airway hyperresponsiveness (AHR). The histopathological change was studied to assess lung tissue inflammation. Cell counts in bronchoalveolar lavage fluid (BALF) were also tested to represent airway inflammation. IL-4 and CXCL1 in BALF and serum were also used to evaluate the airway inflammation. Histone deacelytase2 (HDAC2) activity of lung tissues was measure by assay kit. HDAC2 expression in the lung tissue had been detected by western blot. RESULTS: Re, RL and Cdyn were monitored to represent airway responsiveness. All of the three indicators in SEA group were significantly different from control group, while clarithromycin improved airway responsiveness and the three indicator were statistically significant (P<0.01). Histopathology observation had showed massive infiltration of inflammatory cells in both OVA group and SEA group, while inflammation infiltration attenuated in CAM group. Total cell counts in SEA group was much higher than that in CAM group (P=0.019), so were neutrophils (P=0.022) and eosinophils (P=0.042); while macrophages in SEA group decreased when compared to CAM group (P=0.026), IL-4 and CXCL1 level in CAM group were significantly decreased in comparison to those in SEA group (P=0.031, P=0.017). HDAC2 activity in SEA group decreased significantly when compared to control group (P=0.010); while HDAC2 activity in CAM group was improved and significantly better than that in SEA group (P=0.038). The expression of HADC2 in CAM group improved significantly when compared to that in SEA group (P=0.022). CONCLUSIONS: Clarithromycin could improve AHR and attenuate airway inflammation in smoke exposed asthmatic mice which may involve HDAC2. Macrolides might have the potential to serve as the adjunctive treatment to some refractory asthmatics who are smokers or passive smokers. PMID- 26380736 TI - Urinary excretion of 9alpha,11beta-prostaglandin F2 and leukotriene E4 in patients with exercise-induced bronchoconstriction. AB - BACKGROUND: Increased levels of mast cell-derived eicosanoids, such as prostaglandin (PG) D2 and cysteinyl leukotrienes (CysLTs), have been reported in patients with exercise-induced bronchoconstriction (EIB), suggesting that mast cell activation is involved in the mechanism of EIB. However, it is still controversial since these results have not been reproduced in other studies. The aim of this study was to evaluate the role of PGD2 and LTE4 in adult asthma with EIB, as measuring urinary levels of their metabolites-9alpha,11beta-PGF2 and LTE4 before and after an exercise challenge test. METHODS: Eight patients with asthma and EIB and five normal controls without EIB were enrolled. Exercise challenge tests comprised of 6 min of treadmill exercise or free running were performed in all study subjects, and urine samples before and 1 h after the challenge were collected. Urinary levels of 9alpha,11beta-PGF2 and LTE4 were measured by enzyme immunoassay (EIA). RESULTS: No significant differences were observed in 9alpha,11beta-PGF2 and LTE4 levels before/after the exercise challenge between patients with EIB and normal controls. No significant increases in urinary levels of 9alpha,11beta-PGF2 or LTE4 were detected during the exercise challenge in patients with EIB and normal controls. No significant correlations were observed between the percent decrease in forced expiratory volume in 1 s (FEV1) or percent changes in 9alpha,11beta-PGF2 and LTE4 levels after the exercise challenge. CONCLUSIONS: Urinary 9alpha,11beta-PGF2 and LTE4 levels did not increase after an exercise challenge in patients with EIB, suggesting that urinary excretion of 9alpha,11beta-PGF2 and LTE4 may not be a good marker of mast cell activation in patients with EIB. PMID- 26380737 TI - Effectiveness of hemostasis with Foley catheter after vacuum-assisted breast biopsy. AB - BACKGROUND: Interventional bleeding and post-interventional hematoma are the most common complications following vacuum-assisted breast biopsy (VABB). The aim of the current study was to evaluate the effectiveness of Foley catheter-induced hemostasis in VABB. METHODS: A randomized prospective controlled trial was conducted using a total of 437 consecutive 8-gauge ultrasound-guided VABB procedures that were performed in 282 patients from June 2012 to October 2013. In each procedure, hemostasis was induced with either a Foley catheter or with external compression. Bleeding during intervention, hematoma post-intervention and the time of procedure were recorded. Statistical analysis included a Chi Square test and an independent-samples t-test, and P value <0.05 was considered to be significant. RESULTS: Significantly less bleeding and post-interventional hematoma resulted when hemostasis was induced using a Foley catheter vs. compression (7.6% vs. 17.4%, P=0.002; 8.9% vs. 27.9%, P<0.001). The mean time of breast biopsy was significantly less when using a Foley catheter vs. compression (33.6 vs. 45.5 min, P<0.001). No post-procedural infectious was encountered. In stratification analysis, there were no significantly different bleeding rates between the Foley catheter and compression methods in cases of single lesions (6.7% vs. 14.1%, P=0.346). In cases of multiple lesions, the Foley catheter method produced less bleeding/hematoma than compression (10.4% vs. 47.4%, P=0.018; 16.7% vs. 52.6%, P=0.020). Whether using a Foley catheter or compression to induce hemostasis, no significant difference was found in the rate of bleeding or hematoma when lesions <15 mm were removed (3.8% vs. 6.1%, P=0.531; 6.1% vs. 11.4%, P=0.340). When lesions >=15 mm were excised, the rates of interventional bleeding and post-interventional hematoma were significantly lower in the Foley catheter study group than the compression control group (12.5% vs. 32.2%, P=0.034; 12.5% vs. 49.4%, P<0.001). There was significantly less bleeding (P=0.004) and hematoma (P<0.001) in the upper external quadrant when using a Foley catheter compared with compression (4.5% vs. 15.7%, P=0.004; 9.8% vs. 40.2%, P<0.001), but no significant differences for other quadrants. CONCLUSIONS: Inducing hemostasis with a Foley catheter after VABB is a very effective and safe alternative to hemostasis with compression. PMID- 26380738 TI - Female breast cancer incidence and mortality in 2011, China. AB - BACKGROUND: Breast cancer is the most common cancer diagnosis in women. During the past 30 years, mortality of breast cancer in Chinese women showing a gradual upward trend, it has become the crucial death reasons of female. METHODS: In 2014, there were 234 population-based cancer registries submitting their data of 2011 to the National Central Cancer Registry (NCCR) of China and 177 cancer registries' data were selected after quality evaluation. The selected cancer registries were classified as urban areas and rural areas, in each level. The crude incidence and mortality rates of female breast cancer were calculated by age-groups. Age-standardized rates were described by China and World standard population. And the national population data of China was used to combine with the cancer registries' data to estimate the female breast cancer burden in 2011 in China. RESULTS: The estimated number of female breast cancer cases was 248,620. The crude incidence rate, age-standardized rate by China and World population were 37.86 per 100,000, 28.51 per 100,000 and 26.65 per 100,000, respectively. The estimated number of female breast cancer death in 2011 of China was about 60,473. The crude, age-standardized mortalities by China population and World population were 9.21 per 100,000, 6.57 per 100,000 and 6.38 per 100,000, respectively. The incidence and mortality rates were both higher in urban areas than rural areas. Trend of age-specific incidence rates in urban and rural was similar, reaching peak at 55-59 years old. The trend of age-specific mortality rates was very similar before 60 between urban and rural areas, but after that, the urban areas curve was rapidly mounting as the age growing and much higher than rural. CONCLUSIONS: Breast cancer is still a major health burden for Chinese women especially in urban areas. Prevention strategies such as weight control, high-quality screening, diagnosis and treatment may help control the disease. PMID- 26380739 TI - Clinical experience with titanium mesh in reconstruction of massive chest wall defects following oncological resection. AB - OBJECTIVES: To present our experience of reconstructing wide defects with porously titanium mesh after radical resection of malignant chest wall tumors. METHODS: A retrospective review of surgical reconstruction for large chest wall resections with titanium mesh was conducted from January 2009 to August 2014 in Shanghai Chest Hospital. RESULTS: A total of 27 patients underwent major chest wall reconstructions with titanium mesh, following oncological resections. Chest wall sarcomas were the most frequent (63.0%). The mean tumor size was 72.4 (range, 36-140) cm(2). The average size of the applied porously titanium mesh was 140.9 (range, 80-225) cm(2). Mean postoperative length of stay was 7.1 (range, 4 14) days. There were no perioperative mortalities. Four (14.8%) patients experienced treatable complications. All had a resection of at least 3 ribs (median 3, mean 3.5 ribs). A total of 22 patients underwent ribs without sternal resections, and five patients underwent partial sternal resections with adjacent costal cartilage. Anterior chest wall resections were performed in 13 patients while lateral chest wall resections were performed in 9 patients. Three patients had extended resections beyond the chest wall in patients with primary chest wall malignancies, including two with wedge resections of lung and one with partial resection of pericardium. No patient was lost to follow-up. Mean follow-up was 30.7 months. Neither chest wall instability nor wound infection/necrosis was observed. Of these, 23 patients (85.2%) were alive at the last follow-up. Local recurrence was detected in three cases. The 5-year disease-free and overall survivals of primary chest tumors were 72.1% and 80.8%, respectively. CONCLUSIONS: Our results showed that chest wall reconstruction utilizing synthetic titanium meshes following extensive resections of the chest wall malignant tumors allowed adequate resection size, with acceptable complications and survival benefits. PMID- 26380740 TI - Mediastinoscopic esophagectomy for patients with early esophageal cancer. AB - OBJECTIVE: The purpose of this study was to detect the feasibility, safety, and effectiveness of mediastinoscopic esophagectomy for early esophageal cancer. METHODS: The clinical data of 194 patients who underwent mediastinoscopic esophagectomy for early esophageal cancer in our center from December 2005 to October 2014 were retrospectively analyzed. RESULTS: All the surgery was performed successfully. The average duration of thoracic surgery was 48.2+/-7.8 min and the average intra-operative blood loss was 128.1+/-34.5 mL. An average of 3.1+/-1.6 lymph node stations were dissected, with an average number of dissected lymph nodes being 9.38+/-6.2, among which 4.2+/-5.4 were mediastinal lymph nodes. No peri-operative mortality was noted, and the rate of peri-operative morbidity was 13.4%. The median duration of follow-up was 39 [3-108] months, and the overall survival was 72.73%. The overall survival rates significantly differed among different T stages; more specifically, the 5-year survival was 95.23% in patients with stage T1a esophageal cancer, 70.15% for T1b, and 55.56% for T2 (P<0.001). The overall survival was significantly better in patients with negative lymph nodes than those with lymph nodes metastasis (P=0.003); more specifically, the 5-year survival rate was 84.9% for N0, 62.5% for N1, and 50.0% for N2 + N3. CONCLUSIONS: The mediastinoscopic esophagectomy can achieve a similar effectiveness as the conventional thoracoscopic surgery for patients with early stage esophageal cancer. PMID- 26380741 TI - Single-port video-assisted thoracoscopic surgery lung resection: experiences in Fujian Medical University Union Hospital. AB - Video-assisted thoracoscopic surgery (VATS) is currently a better choice than thoracotomy for lung resection, and then single-port VATS has been increasingly applied in clinical settings with the improvements in both endoscopic instruments and surgical skills. Our center began to perform single-port VATS lobectomy in May 2014 and had performed all sort of lung resection in 168 patients till December 2014, including wedge resection, routine lobectomy, sleeve lobectomy, segmentectomy and pneumonectomy. All these procedures were successfully performed without any severe complication. We believe the single-port VATS lung resection is a safe and feasible procedure after surgery practice. PMID- 26380742 TI - From open to single port video-assisted thoracoscopic lobectomy: a stepwise and return progression of the experience from Department of Thoracic Surgery, General Hospital of Guangzhou Military Command of P.L.A. PMID- 26380743 TI - A video demonstration of the Li's anastomosis-the key part of the "non-tube no fasting" fast track program for resectable esophageal carcinoma. AB - The main obstacle of fast track surgery for esophagectomy is early oral feeding. The main concern of early oral feeding is the possibility of increasing the incidence of anastomotic leakage. Dr. Yin Li used the Li's anastomosis to ensure oral feeding at will the first day after esophagectomy. This safe and efficient anastomosis method significantly reduced the anastomotic leak rate, the number of post-operative days and stricture. Importantly, the "non-tube no fasting" fast track program for esophageal cancer patients was conducted smoothly with Li's anastomosis. This article was focused on the surgical procedure of Li's anastomosis. PMID- 26380744 TI - Strategy analysis of cardiopulmonary resuscitation training in the community. AB - Bystander cardiopulmonary resuscitation (CPR) is a crucial therapy for sudden cardiac arrest. This appreciation produced immense efforts by professional organizations to train laypeople for CPR skills. However, the rate of CPR training is low and varies widely across communities. Several strategies are used in order to improve the rate of CPR training and are performed in some advanced countries. The Chinese CPR training in communities could gain enlightenment from them. PMID- 26380746 TI - Some tips about statistics on medical research. PMID- 26380745 TI - Extra Corporeal Membrane Oxygenation (ECMO) review of a lifesaving technology. AB - Extra Corporeal Membrane Oxygenation (ECMO) indications and usage has strikingly progressed over the last 20 years; it has become essential tool in the care of adults and children with severe cardiac and pulmonary dysfunction refractory to conventional management. In this article we will provide a review of ECMO development, clinical indications, patients' management, options and cannulations techniques, complications, outcomes, and the appropriate strategy of organ management while on ECMO. PMID- 26380747 TI - Primary squamous cell carcinoma in the chest wall mimicking abscess. AB - We report a case of squamous cell carcinoma (SCC) presenting a painful cystic mass which originated from the chest wall with bony destructions. The patient underwent complete excision with chest wall reconstruction. Although the imaging characteristics of chest wall tumor can be variable, SCC should be considered in differential diagnosis in the case of symptomatic cystic mass in elderly patients. PMID- 26380748 TI - Bilateral multiple intrapulmonary nodules: a puzzled and rare disease. AB - Primary intrapulmonary spindle cell thymomas (PISCT) are rare lesions that may be mistaken for a variety of benign and malignant epithelial or mesenchymal tumors. It is thought as one subtype of primary intrapulmonary thymomas (PIT). To the best of our knowledge, no bilateral multiple primary intrapulmonary spindle thymomas and treatment had been reported in literature. We fortunately diagnosed and managed this unique case, which might provide some experience for physicians who were interested in this disease. PMID- 26380749 TI - Right lung cancer with partial anomalous pulmonary venous return and absent right upper lobe. AB - When a vascular shunt is present, major lung resection may cause acute right heart failure. We report a case of right lung cancer with ipsilateral partial anomalous pulmonary venous return (PAPVR) and absent right upper lobe managed by pneumonectomy. A 48-year-old former smoker was diagnosed as right lung cancer; chest computed tomography (CT) revealed an anomalous right pulmonary vein draining into inferior vena cava. Bronchus of right upper lobe was not found in fiberoptic bronchoscopy. Right pneumonectomy was performed. Pathological examination revealed a T2aN2M0 squamous lung cancer. The patient tolerated well without notable descending of arterial oxygen pressure. PMID- 26380750 TI - Anemia resolved by thoracoscopic resection of a mediastinal mass: a case report of unicentric Castleman's disease. AB - Castleman's disease (CD) is an uncommon benign lymphoproliferative disorder that usually presents as a single or multiple mediastinal mass. In unicentric CD, constitutional symptoms are rare, but are curable with surgical resection. However, serious intraoperative bleeding often requires conversion to thoracotomy. We present a case of unicentric CD in a 25-year-old woman with anemia, who was successfully treated by thoracoscopic resection. We describe the clinical course from the initial presentation to diagnosis and surgical cure. PMID- 26380751 TI - Transcatheter arterial embolization for intercostal arterial bleeding in a patient after chest tube insertion. AB - Retrograde tube radiography is commonly used in cholangiography and pyelography. We present a case of massive chest tube bleeding 10 days after tube insertion with no noted contrast extravasation on contrast enhanced chest CT with active bleeding detected by retrograde radiography via the chest tube. Subsequent transcatheter arterial embolization (TAE) was successfully performed as a definitive treatment to stop active bleeding. We consider that retrograde tube radiography may be an alternative diagnostic method for patients with active bleeding from a drainage tube, helping to localize bleeding points and presenting TAE an attractive, minimally invasive and effective treatment modality for intercostal artery rupture. PMID- 26380752 TI - A late visceral hernia after diaphragmatic flap coverage of the bronchial stump. AB - A 54-year-old man presented with sudden and severe abdominal pain, and vomiting. He had underwent a right pneumonectomy with bronchial stump reinforcement using diaphragmatic muscle flap 9 years ago, due to non-small cell lung cancer after neoadjuvant chemotherapy. A right partial visceral herniation had been detected 5 years ago during the follow-up which was not present at previous visits. He had refused any surgical intervention since he had been asymptomatic. The chest computed tomography demonstrated visceral herniation. The patient underwent an urgent operation via thoracoabdominal incision to repair the herniation. This type of late catastrophic complication of diaphragmatic muscle flap reinforcement is extremely rare. PMID- 26380754 TI - Erratum to Study on risk factors and phenotypes of acute exacerbations of chronic obstructive pulmonary disease in Guangzhou, China-design and baseline characteristics. AB - [This corrects the article on p. 720 in vol. 7, PMID: 25973239.]. PMID- 26380753 TI - Exponential growth of publications on carbon nanodots by Chinese authors. AB - Publication statistics was retrieved on carbon nanodots (C-dots) from 2004 up till 2014 using the web of Science(TM) search engine. The number of publications from Chinese authors increased exponentially during this period. Till 2014 China mainland authors contributed 47% of the total publications. Publications on pharmacology and toxicology lagged far behind the publications on chemistry and material science, indicating that research is not solidly moving toward the direction of application. PMID- 26380755 TI - Sleep apnoea: a major and under-recognised public health concern. PMID- 26380756 TI - Chronic hypoventilation syndromes and sleep-related hypoventilation. AB - Chronic hypoventilation affects patients with disorders on any level of the respiratory system. The generation of respiratory impulses can be impaired in congenital disorders, such as central congenital alveolar hypoventilation, in alterations of the brain stem or complex diseases like obesity hypoventilation. The translation of the impulses via spinal cord and nerves to the respiratory muscles can be impaired in neurological diseases. Thoraco-skeletal or muscular diseases may inhibit the execution of the impulses. All hypoventilation disorders are characterized by a reduction of the minute ventilation with an increase of daytime hypercapnia. As sleep reduces minute ventilation substantially in healthy persons and much more pronounced in patients with underlying thoraco-pulmonary diseases, hypoventilation manifests firstly during sleep. Therefore, sleep related hypoventilation may be an early stage of chronic hypoventilation disorders. After treatment of any prevailing underlying disease, symptomatic therapy with non-invasive ventilation (NIV) is required. The adaptation of the treatment should be performed under close medical supervision. Pressure support algorithms have become most frequently used. The most recent devices automatically apply pressure support and vary inspiratory and expiratory pressures and breathing frequency in order to stabilize upper airways, normalize ventilation, achieve best synchronicity between patient and device and aim at optimizing patients' adherence. PMID- 26380757 TI - Emerging technology: electrical stimulation in obstructive sleep apnoea. AB - Electrical stimulation (ES) of the upper airway (UAW) dilator muscles for patients with obstructive sleep apnoea (OSA) has been used for several decades, but in recent years research in this field has experienced a renaissance; the results of several studies have triggered a steady rise in the interest in this topic. Prospective trials, although still lacking a sham-controlled and randomised approach, have revealed the potential of ES. Hypoglossal nerve stimulation (HNS) leads to a significant reduction in the apnoea-hypopnoea index and the oxygen desaturation index (ODI). There are similar results published from feasibility studies for transcutaneous ES. A limitation of HNS remains the invasive procedure, the costs involved and severe adverse events, while for the non-invasive approach complications are rare and limited. The limiting step for transcutaneous ES is to deliver a sufficient current without causing arousal from sleep. Despite the progress up to date, numerous variables including optimal stimulation settings, different devices and procedures remain to be further defined for the invasive and the non-invasive method. Further studies are required to identify which patients respond to this treatment. ES of the UAW dilator muscles in OSA has the potential to develop into a clinical alternative to continuous positive airway pressure (CPAP) therapy. It could benefit selected patients who fail standard therapy due to poor long-term compliance. It is likely that international societies will need to review and update their existing guidance on the use of ES in OSA. PMID- 26380758 TI - Respiratory sleep disorders in patients with congestive heart failure. AB - Respiratory sleep disorders (RSD) occur in about 40-50% of patients with symptomatic congestive heart failure (CHF). Obstructive sleep apnea (OSA) is considered a cause of CHF, whereas central sleep apnea (CSA) is considered a response to heart failure, perhaps even compensatory. In the setting of heart failure, continuous positive airway pressure (CPAP) has a definite role in treating OSA with improvements in cardiac parameters expected. However in CSA, CPAP is an adjunctive therapy to other standard therapies directed towards the heart failure (pharmacological, device and surgical options). Whether adaptive servo controlled ventilatory support, a variant of CPAP, is beneficial is yet to be proven. Supplemental oxygen therapy should be used with caution in heart failure, in particular, by avoiding hyperoxia as indicated by SpO2 values >95%. PMID- 26380759 TI - Obstructive sleep apnea is a common disorder in the population-a review on the epidemiology of sleep apnea. AB - The prevalence of obstructive sleep apnea (OSA) defined at an apnea-hypopnea index (AHI) >=5 was a mean of 22% (range, 9-37%) in men and 17% (range, 4-50%) in women in eleven published epidemiological studies published between 1993 and 2013. OSA with excessive daytime sleepiness occurred in 6% (range, 3-18%) of men and in 4% (range, 1-17%) of women. The prevalence increased with time and OSA was reported in 37% of men and in 50% of women in studies from 2008 and 2013 respectively. OSA is more prevalent in men than in women and increases with age and obesity. Smoking and alcohol consumption are also suggested as risk factors, but the results are conflicting. Excessive daytime sleepiness is suggested as the most important symptom of OSA, but only a fraction of subjects with AHI >5 report daytime sleepiness and one study did not find any relationship between daytime sleepiness and sleep apnea in women. Stroke and hypertension and coronary artery disease are associated with sleep apnea. Cross-sectional studies indicate an association between OSA and diabetes mellitus. Patients younger than 70 years run an increased risk of early death if they suffer from OSA. It is concluded that OSA is highly prevalent in the population. It is related to age and obesity. Only a part of subjects with OSA in the population have symptoms of daytime sleepiness. The prevalence of OSA has increased in epidemiological studies over time. Differences and the increase in prevalence of sleep apnea are probably due to different diagnostic equipment, definitions, study design and characteristics of included subjects including effects of the obesity epidemic. Cardiovascular disease, especially stroke is related to OSA, and subjects under the age of 70 run an increased risk of early death if they suffer from OSA. PMID- 26380761 TI - Insulin resistance, glucose intolerance and diabetes mellitus in obstructive sleep apnoea. AB - Obstructive sleep apnoea (OSA) is a highly prevalent disorder, which conveys an increased risk of cardiovascular disease and death. Type 2 diabetes mellitus (T2DM), glucose intolerance and insulin resistance (IR) are common in subjects with OSA, but a shared intimate relationship with obesity makes discerning an independent link challenging. Nonetheless, mechanistic studies suggest that OSA could contribute to impaired glucose metabolism via the effects of sleep fragmentation, sympathetic excitation and intermittent hypoxia (IH) on pancreatic B-cell function, insulin sensitivity, and systemic inflammation. In particular, emerging data suggest that IH may have an important detrimental effect on adipose tissue function and inflammation. Similarly, data from population-and clinic level studies suggest that OSA is independently related with the prevalence and incidence of T2DM and IR, and may also lead to worse glycaemic control in diabetics. However, the ability of continuous positive airway pressure (CPAP) therapy to make a meaningful impact on T2DM or IR remains uncertain. In this review we explore the available evidence linking OSA with IR, glucose intolerance and T2DM, and discuss potential pathobiological mechanisms by which sleep disordered breathing can affect metabolic health. PMID- 26380760 TI - New developments in the use of positive airway pressure for obstructive sleep apnea. AB - Obstructive sleep apnea (OSA) is a disorder which afflicts a large number of individuals around the world. OSA causes sleepiness and is a major cardiovascular risk factor. Since its inception in the early 1980's, continuous positive airway pressure (CPAP) has emerged as the major treatment of OSA, and it has been shown to improve sleepiness, hypertension, and a number of cardiovascular indices. Despite its successes, adherence with treatment remains a major limitation. Herein we will review the evidence behind the use of positive airway pressure (PAP) therapy, its various modes, and the methods employed to improve adherence. We will also discuss the future of PAP therapy in OSA and personalization of care. PMID- 26380763 TI - Diagnostic approaches to respiratory sleep disorders. AB - Sleep disordered breathing (SDB) comprises a number of breathing disturbances occurring during sleep including snoring, the obstructive sleep apnoea/hypopnea syndrome (OSAHS), central sleep apnoea (CSA) and hypoventilation syndromes. This review focuses on sleep disordered breathing and diagnostic approaches in adults, in particular clinical assessment and overnight assessment during sleep. Although diagnostic approaches to respiratory sleep disorders are reasonably straightforward, they do require a degree of clinical acumen when it comes to assessing severity and management options. Diagnosing respiratory sleep disorders on clinical features alone has limitations. Monitoring and measuring respiration during sleep has undergone many advances in the last 40 years in respect of quality and validity, largely regarding OSAHS. Despite the improvement in our diagnostic standards and recognition of sleep disordered breathing, many limitations still need to be overcome. Apart from assessing the individual patient, population screening for sleep disorders continues to preoccupy health professionals and policy makers in many countries. Research in the field is pushing current boundaries in terms of simplifying diagnosis and enhancing screening for sleep disordered breathing in large populations. At present, a number of these newer approaches require further validation. PMID- 26380762 TI - The pathogenesis of obstructive sleep apnea. AB - Obstructive sleep apnea (OSA) is a major source of cardiovascular morbidity and mortality, and represents an increasing burden on health care resources. Understanding underlying pathogenic mechanisms of OSA will ultimately allow for the development of rational therapeutic strategies. In this article, we review current concepts about the pathogenesis of OSA. Specifically, we consider the evidence that the upper airway plays a primary role in OSA pathogenesis and provide a framework for modelling its biomechanical properties and propensity to collapse during sleep. Anatomical and neuromuscular factors that modulate upper airway obstruction are also discussed. Finally, we consider models of periodic breathing, and elaborate generalizable mechanisms by which upper airway obstruction destabilizes respiratory patterns during sleep. In our model, upper airway obstruction triggers a mismatch between ventilatory supply and demand. In this model, trade-offs between maintaining sleep stability or ventilation can account for a full range of OSA disease severity and expression. Recurrent arousals and transient increases in airway patency may restore ventilation between periods of sleep, while alterations in neuromuscular and arousal responses to upper airway obstruction may improve sleep stability at still suboptimal levels of ventilation. PMID- 26380764 TI - Risk factors for acute kidney injury in overweight patients with acute type A aortic dissection: a retrospective study. AB - BACKGROUND: To identify risk factors for acute kidney injury (AKI) in overweight patients who underwent surgery for acute type A aortic dissection (TAAD). METHODS: A retrospective study including 108 consecutive overweight patients [body mass index (BMI) >=24] between December 2009 and April 2013 in Beijing Anzhen Hospital has been performed. AKI was defined by Acute Kidney Injury Network (AKIN) criteria, which is based on serum creatinine (sCr) or urine output. RESULTS: The mean age of the patients was 43.69+/-9.66 years. Seventy-two patients (66.7%) developed AKI during the postoperative period. A logistic regression analysis was performed to identify two independent risk factors for AKI: elevated preoperative sCr level and 72-h drainage volume. Renal replacement therapy (RRT) was required in 15 patients (13.9%). The overall postoperative mortality rate was 7.4%, 8.3% in AKI group and 5.6% in non-AKI group. There is no statistically significant difference between the two groups (P=0.32). CONCLUSIONS: A higher incidence of AKI (66.7%) in overweight patients with acute TAAD was confirmed. The logistic regression model identified elevated preoperative sCr level and 72-h drainage volume as independent risk factors for AKI in overweight patients. We should pay more attention to prevent AKI in overweight patients with TAAD. PMID- 26380765 TI - Quantative computerized tomography assessment of lung density as a predictor of postoperative pulmonary morbidity in patients with lung cancer. AB - BACKGROUND: The aim of this study was to evaluate the pulmonary reserve of the patients via preoperative quantitative computerized tomography (CT) and to determine if these preoperative quantitative measurements could predict the postoperative pulmonary morbidity. METHODS: Fifty patients with lung cancer who underwent lobectomy/segmentectomy were included in the study. Preoperative quantitative CT scans and pulmonary function tests data were evaluated retrospectively. We compare these measurements with postoperative morbidity. RESULTS: There were 32 males and 18 females with a mean age of 54.4+/-13.9 years. Mean total density was -790.6+/-73.4 HU. The volume of emphysematous lung was (< 900 HU) 885.2+/-1,378.4 cm(3). Forced expiratory volume in one second (FEV1) (r= 0.494, P=0.02) and diffusion capacity of carbon monoxide (DLCO) (r=-0.643, P<0.001) were found to be correlate with the volume of emphysematous lung. Furthermore FEV1 (r=0.59, P<0.001) and DLCO (r=0.48, P<0.001) were also found to be correlate with mean lung density. Postoperative pulmonary morbidity was significantly higher in patients with lower lung density (P<0.001), larger volume of emphysema (P<0.001) and lower DLCO (P=0.039). A cut-off point of -787.5 HU for lung density showed 86.96% sensitivity and 81.48% specificity for predicting the pulmonary morbidity (kappa =-0.68, P<0.001). Additionally a cut-off point of 5.41% for emphysematous volume showed 84.00% sensitivity and 80.00% specificity for predicting the pulmonary morbidity (kappa =0.64, P<0.001). According to logistic regression analyses emphysematous volume >5.41% (P=0.014) and lung density <-787.5 HU (P=0.009) were independent prognostic factors associated with postoperative pulmonary morbidity. CONCLUSIONS: In this study, the patients with a lower lung density than -787.5 HU and a higher volume of emphysema than 5.41% were found to be at increased risk for developing postoperative pulmonary morbidity. More stringent precautions should be taken in those patients that were found to be at high risk to avoid pulmonary complications. PMID- 26380767 TI - Bronchial artery embolization for malignant hemoptysis: a single institutional experience. AB - OBJECTIVE: To assess the effectiveness of bronchial artery embolization (BAE) in patients with malignant hemoptysis. METHODS: An IRB-approved retrospective study at our academic institution was conducted on all patients treated by BAE for hemoptysis from lung malignancy. Outcome and safety measures were documented according to Society of Interventional Radiology (SIR) practice guidelines. RESULTS: A total of 26 patients (13 male, 13 female) with lung malignancy underwent BAE for hemoptysis from 2003-2013. Histologic analysis revealed 80% (21/26) of cases were from primary lung malignancies, while the remaining 20% (4/26) represented metastatic disease. Sixty-five percent (17/26) of patients underwent bronchoscopy prior to BAE. Follow-up ranged from 2 to 1,909 days, with average of 155 days. Technical success was achieved in 77% of patients (20/26). Clinical success rate was 75% (15/20). Eighty-five percent of embolized patients (17/20) were treated with particles, 15% (3/20) with gelfoam, and 20% (4/20) with coils. Single-vessel embolization was performed in 70% (14/20), two-vessel in 20% (4/20), and multiple vessels in 10% (2/20). No complications were reported. Six month all-cause mortality of treated cases was 55% (11/20) with an in-hospital mortality of 25% (5/20). Ten percent (2/20) had remote re-bleeding events beyond 6 months. Statistically significant predictors of mortality were intubation status, hemoglobin/hematocrit at presentation, and thrombocytopenia. CONCLUSIONS: BAE is a safe and useful treatment for clinically significant hemoptysis in patients with primary or metastatic lung masses despite high overall mortality. Intubation status, low hemoglobin/hematocrit, and thrombocytopenia may represent clinical predictors of short term mortality following BAE. ADVANCES IN KNOWLEDGE: Most patients undergoing BAE for malignant hemoptysis achieve high clinical success despite suffering a high mortality from underlying disease. PMID- 26380766 TI - Identification of immunohistochemical markers for distinguishing lung adenocarcinoma from squamous cell carcinoma. AB - BACKGROUND: Immunohistochemical staining has been widely used in distinguishing lung adenocarcinoma (LUAD) from lung squamous cell carcinoma (LUSC), which is of vital importance for the diagnosis and treatment of lung cancer. Due to the lack of a comprehensive analysis of different lung cancer subtypes, there may still be undiscovered markers with higher diagnostic accuracy. METHODS: Herein first, we systematically analyzed high-throughput data obtained from The Cancer Genome Atlas (TCGA) database. Combining differently expressed gene screening and receiver operating characteristic (ROC) curve analysis, we attempted to identify the genes which might be suitable as immunohistochemical markers in distinguishing LUAD from LUSC. Then we detected the expression of six of these genes (MLPH, TMC5, SFTA3, DSG3, DSC3 and CALML3) in lung cancer sections using immunohistochemical staining. RESULTS: A number of genes were identified as candidate immunohistochemical markers with high sensitivity and specificity in distinguishing LUAD from LUSC. Then the staining results confirmed the potentials of the six genes (MLPH, TMC5, SFTA3, DSG3, DSC3 and CALML3) in distinguishing LUAD from LUSC, and their sensitivity and specificity were not less than many commonly used markers. CONCLUSIONS: The results revealed that the six genes (MLPH, TMC5, SFTA3, DSG3, DSC3 and CALML3) might be suitable markers in distinguishing LUAD from LUSC, and also validated the feasibility of our methods for identification of candidate markers from high-throughput data. PMID- 26380768 TI - Randomized controlled trials of induction treatment and surgery versus combined chemotherapy and radiotherapy in stages IIIA-N2 NSCLC: a systematic review and meta-analysis. AB - BACKGROUND: The efficacy of induction treatment plus surgery for improving postoperative survival in patients with non-small-cell lung cancer (NSCLC) in stages IIIA-N2 is controversial, especially compared with the combined chemotherapy and radiotherapy. We therefore performed a systematic review and meta-analysis of the published phase III randomized clinical trials (RCTs) to quantitatively evaluate the survival benefit of preoperative induction treatment vs. combined chemoradiotherapy. METHODS: We systematically searched for trials that started after January, 1980. We excluded relevant studies using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) standards. Our primary endpoint, overall survival (OS), was defined as the time from randomisation until death (any cause). Secondary endpoint was progression free survival (PFS). PubMed, EMBASE and Cochrane library were used for the study search. All analyses were by intention to treat. RESULTS: Three studies (1,084 patients) were centrally selected and analyzed for the present meta-analysis. Combination of the three randomized controlled trials showed that there was no significant benefit of induction treatment plus surgery compared to combined chemoradiotherapy on 2-year OS [risk ratio (RR) =1.00; 95% CI, 0.85-1.17; P=0.98] and 4-year OS (RR =1.13; 95% CI, 0.85-1.51; P=0.39). However, from the subgroup analysis, it showed a significant PFS benefit (RR =1.78; 95% CI, 1.08-2.92; P=0.02) regarded chemoradiotherapy as preoperative induction treatment, compared with chemotherapy alone for induction treatment (PFS) (RR =1.05; 95% CI, 0.61 1.81; P=0.86). CONCLUSIONS: There was no significant OS benefit of induction treatment plus surgery compared with combined chemoradiotherapy in patients with NSCLC (stages IIIA-pN2) at 2 and 4 years. However, we could conclude PFS could be improved when radiation therapy was added into preoperative induction treatment. Given the potential advantages of adding radiation preoperatively, clinicians should consider using this treatment strategy in the stage IIIA-N2 disease after fully assessment of the patients. PMID- 26380769 TI - Vitamin D binding protein gene polymorphisms and chronic obstructive pulmonary disease: a meta-analysis. AB - BACKGROUND: A number of polymorphisms in vitamin D binding protein (VDBP) (GC) gene have been implicated in risk of chronic obstructive pulmonary disease (COPD), but the results were controversial. GC1F, GC1S, and GC2 are three common variants of the VDBP gene [single nucleotide polymorphisms (SNPs): rs7041 and rs4588], which were reported to be associated with COPD. This study aimed to explore the association between VDBP gene polymorphisms and COPD. METHODS: PubMed, EMBASE, Web of Science (Medline) and Chinese National Knowledge Infrastructure (CNKI) were searched for eligible case-control studies. Study quality was evaluated using the Newcastle-ottawa quality assessment scale (NOS). After the most appreciated genetic model was identified, a meta-analysis was performed to test the association between VDBP gene polymorphism and COPD. The pooled odds ratios (ORs) were performed respectively for the most appreciated genetic model, single allele comparison and homozygous gene model analysis. Summary receiver operating characteristic curve (SROC) analyses were applied to evaluate the diagnostic performance of polymorphism of VDBP to COPD. RESULTS: Eight studies containing 2,216 participants were included. The analyses of the most appropriate genetic models offered significant results in recessive model of GC1F/1S group (OR =2.18), co-dominant genetic model in GC1F/2 group (1F-1F vs. 2 2: OR =4.87; 1F-2 vs. 2-2: OR =1.73; 1F-1F vs. 1F-2: OR =2.27). In single allele comparison, significant results were obtained in GC1F vs. GC1S and GC1F vs. GC2, with ORs were 1.47 and 1.77, respectively. In homozygous genes comparison, the OR was 2.51 in GC1F homozygote vs. other genotypes. Subgroup analyses offered the same significant results in Asian population, but not in Caucasian population. The SROC analyses showed the less accurate performance of polymorphism of VDBP to COPD. CONCLUSIONS: There is a close association between COPD and GC gene polymorphisms. The GC1F allele could be a risk factor, the GC1S and GC2 allele may be protective factors in Asian, but not in Caucasians. PMID- 26380770 TI - Prognostic factors for resection of isolated pulmonary metastases in breast cancer patients: a systematic review and meta-analysis. AB - BACKGROUND: Lung is a common organ of metastases in patients with primary breast cancer. Pulmonary metastasis of primary breast cancer is usually considered as a systemic disease, however, the systemic approaches have achieved little progress in terms of prolonging survival time. In contrast, some studies revealed a probable survival benefit of pulmonary metastasectomy for such patients. However, the prognostic factor for pulmonary metastasectomy in breast cancer patients is still a controversial issue. The aim of this study was to conduct a systematic review and meta-analysis of cohort studies to assess the pooled 5-year overall survival (OS) rate and the prognostic factors for pulmonary metastasectomy from breast cancer. METHODS: An electronic search in MEDLINE (via PubMed), EMBASE (via OVID), CENTRAL (via Cochrane Library), and Chinese BioMedical Literature Database (CBM) complemented by manual searches in article references were conducted to identify eligible studies. All cohort studies in which survival and/or prognostic factors for pulmonary metastasectomy from breast cancer were reported were included in the analysis. We calculated the pooled 5-year survival rates, identified the prognostic factors for OS and combined the hazard ratios (HRs) of the identified prognostic factors. RESULTS: Sixteen studies with a total of 1937 patients were included in this meta-analysis. The pooled 5-year survival rates after pulmonary metastasectomy was 46% [95% confidence interval (95% CI): 43 49%]. The poor prognostic factors were disease-free interval (DFI) (<3 years) with HR =1.70 (95% CI: 1.37-2.10), resection of metastases (incomplete) with HR =2.06 (95% CI: 1.63-2.62), No. of pulmonary metastases (>1) with HR =1.31 (95% CI: 1.13-1.50) and the hormone receptor status of metastases (negative) with HR =2.30 (95% CI: 1.43-3.70). CONCLUSIONS: Surgery with a relatively high 5-year OS rate after pulmonary metastasectomy (46%), may be a promising treatment for pulmonary metastases in the breast cancer patients with a good performance status and limited disease. The main poor prognostic factors were DFI (<3 years), resection of metastases (incomplete), No. of pulmonary metastasis (>1) and hormone receptor status of metastases (negative). And prospective randomized trials will be needed to address these issues in the future. PMID- 26380771 TI - Surgical treatment for pulmonary tuberculosis: is video-assisted thoracic surgery "better" than thoracotomy? AB - OBJECTIVE: To compare video-assisted thoracoscopic surgery (VATS) lobectomy and conventional open lobectomy in patients with pulmonary tuberculosis (TB) who require surgery. METHODS: Forty patients with pulmonary TB who required lobectomy were randomized to receive either VATS or open lobectomy. Patient demographic, pulmonary function, operative, and postoperative data were compared between the groups. RESULTS: There were 20 patients who received VATS lobectomy (median age 31.5 years, range 19-67 years) and 20 that received open lobectomy (median age 33.5 years, range 16-60 years). The two groups were similar with respect to gender, age and pulmonary function (all, P>0.05). Lobectomy was completed by VATS in 19 of 20 patients (95%), and by thoracoscope-assisted mini-incision lobectomy in 1 patient. The median intraoperative blood loss was 345 mL (range, 100-800 mL), and the median duration of pleural cavity closed drainage was 5 days (range, 3-7 days). All open lobectomies were completed successfully, and the median intraoperative blood loss was 445 mL (range, 150-950 mL) and the median duration of pleural cavity closed drainage was 5 days (range, 3-9 days). No statistically significant differences were found between the groups with respect to operation completion rates, type of lung resection, intraoperative blood loss, closed pleural drainage duration and volume of postoperative chest drainage. The operation time, number of postoperative complications, postoperative pain index at 24 hours after surgery and postoperative hospital stay were all significantly less in the VATS group. With a median follow-up duration of 14 months (range, 8 18 months) no positive sputum examination results were found in either group. CONCLUSIONS: VATS lobectomy is an effective and minimally invasive method for treating patients with pulmonary TB. PMID- 26380772 TI - Functional residual capacity in beagle dogs with and without acute respiratory distress syndrome. AB - BACKGROUND: Traditionally, the choice of tidal volume for mechanical ventilation was based on body weight (BW) and usually, predicted BW was used to correct actual BW inter-individual variations in obesity and muscle weight. The method of selecting tidal volume depended on the fact that normal lung volumes, especially functional residual capacity (FRC), were mainly determined by height (indirectly by predicted BW), sex and age in healthy persons. However, FRCs in patients with acute respiratory distress syndrome (ARDS) might not abide by the same rule and be significantly different from each other in patients with the same height and sex. We hypothesized that FRC was determined by body length (surrogate for predicted BW) and age in healthy male beagle dogs but not in lung injured ones. METHODS: A total of 24 dogs were recruited and ARDS model was induced by intravenous injection of oleic acid. FRC was measured by chest computer tomography. Blood gas analysis, extra vascular lung water and respiratory system mechanics were tested at baseline and post-lung injury. Age, body length and actual BW were also recorded before experiments. RESULTS: After lung injury, FRC decreased sharply from baseline (414+/-84) to (214+/-70) mL. For healthy lungs, FRC could be estimated by the following formula: FRC =21.86 * age (months) + 20.55 * body length (cm) - 1,337.98 (P<0.05), while for injured lungs, the formula of multiple linear regression was invalid (P=0.305). CONCLUSIONS: FRC was linearly related to body length in healthy dogs but not in lung injured ones. The traditional view of setting tidal volume based on predicted BW should be challenged cautiously. PMID- 26380773 TI - Effect of dobutamine on lung aquaporin 5 in endotoxine shock-induced acute lung injury rabbit. AB - BACKGROUND: Dobutamine, a commonly used vasoactive drug, has been reported to reduce pulmonary edema and protect against acute lung injury (ALI) by up regulating aquaporin 5 (AQP5) expressions. However, the underlying mechanism is still elusive. METHODS: ALI was induced by intravenous injection of LPS. Seventy male New Zealand white rabbits were randomly divided into seven groups: sham group, ALI group, dobutamine low-dose group [group ALI + Dob (L)], dobutamine medium-dose group [group ALI + Dob (M)], dobutamine high-dose group [group ALI + Dob (H)], ALI + Dob (H) + ICI group and sham + ICI group. ICI 118,551, a potent and specific beta-2 antagonist, could block the effect of dobutamine. The animals were sacrificed at 3 h after endotoxic shock and lungs were removed. The arterial blood gas was analyzed. The lung wet to dry (W/D) ratio was determined. The level of cyclic AMP (cAMP) in lung tissue was assessed by ELISA. The expression of AQP5 protein was determined by western blotting and immunohistochemistry. The pathological alteration in lung tissue was evaluated by optical microscopy and electron microscope, and lung injury score was assessed. RESULTS: Dobutamine increased AQP5 protein expression and cAMP level in a dose-dependent manner. Meanwhile, the degree of lung pathological and ultrastructural lesion was ameliorated and arterial blood gas was improved obviously. Additionally, W/D ratio and histological scores decreased significantly. However, the AQP5 protein expression and cAMP level were significantly decreased in group ALI + Dob (H) + ICI than that in group ALI + Dob (H), the degree of lung pathological and ultrastructural lesion was more serious in group ALI + Dob (H) + ICI than that in group ALI + Dob (H) and the arterial blood gas was not obviously improved. CONCLUSIONS: These results suggested that protective effect of dobutamine against endotoxin shock-induced ALI may be due to its ability of up-regulating AQP5 protein expression via increasing intracellular cAMP concentration. PMID- 26380774 TI - Endobronchial closure of bronchopleural fistula using Amplatzer device. AB - BACKGROUND: Bronchopleural fistulas (BPF) are a dreaded complication after lobectomy and pneumonectomy and are associated with high morbidity and mortality. BPF are treated by a range of surgical and endoscopic techniques. Amplatzer devices (ADs), normally used for the closure of cardiac defects, may enable the minimally invasive occlusion of these defects. METHODS: Three patients with BPF were treated with the bronchoscopic closure of BPF using AD. Under general anaesthesia, the fistula was located using bronchography and the self-expanding AD was placed under direct bronchoscopic and fluoroscopic guidance into the fistula. Bronchography was used to control the complete occlusion of the BPF. RESULTS: Three male patients with a mean age of 63 years (range, 53-73 years) were successfully treated by AD. Two BPF occurred after lobectomy of the right lower lobe for lung cancer and one after right pneumonectomy for lung cancer. In all patients the bronchoscopic procedure was successful and symptoms of empyema and BPF showed no recurrence over a median follow-up of 22 months. CONCLUSIONS: Endobronchial closure of BPF using AD represents a safe, effective and promising method for postoperative BPF. PMID- 26380775 TI - Incidental bronchial injury by soft coagulation. AB - Soft coagulation is a hemostat system of electrosurgical units, which automatically regulates its output voltage below 200 V, to avoid excessive output that causes carbonization of the target tissue. However, this new minimally invasive technology still has the potential risk of tissue damage during surgery. We encountered three patients with bronchial injury caused by the above system; one of whom had bronchopleural fistula. This is believed to be the first report emphasizing the adverse effects of the soft coagulation system in thoracic surgery, giving a warning to the application of this convenient device. PMID- 26380776 TI - Minimally invasive esophageal resection and intrathoracic anastomosis for lower thoracic esophageal cancer with single position. AB - There are various esophagectomy approaches for lower thoracic esophageal cancer, and the minimally invasive esophagectomy (MIE) approach shows the advantages of less discomfort, shorter length of stay and a faster recovery to baseline status than open approaches. The current study reports a case of lower thoracic esophageal cancer was treated using a single-position, minimally invasive surgical technique with laparoscopy and thoracoscopy. A 68-year-old man, whose gastroscopy identified the esophageal carcinoma, came to our medical center due to dysphagia for over 1 year. The patient underwent tumor radical resection and intrathoracic anastomosis by laparoscopy and thoracoscopy with single position. The patient has recovered well after the surgery. PMID- 26380777 TI - Uniportal VATS-a new era in lung cancer surgery. PMID- 26380778 TI - High-flow oxygen cannula: a very effective method to correct severe hypoxemia. PMID- 26380779 TI - Issues of energy and protein feeding in critically ill: the permissive underfeeding trial. PMID- 26380780 TI - Solitary pure ground-glass nodules measuring 5 mm or less: current imaging management, question and suggestion. PMID- 26380781 TI - (18)F-fluorodeoxyglucose positron emission tomography/computed tomography characterization of solitary pulmonary nodules: can we do better? PMID- 26380782 TI - Chronic total occlusion: no more meta-analysis, please-a randomized clinical trial is urgently needed. PMID- 26380783 TI - Chronic total improvement in ventricular function and survival. AB - Coronary chronic total occlusions (CTOs) represent a frequent lesions' subset observed in everyday catheterization laboratory practice. Previously considered to be an indication for surgical myocardial revascularization, the interest of interventional community in CTOs has exponentially grown during the last decade, particularly thanks to an important development in dedicated equipment and techniques, and has led to the achievement of high rates of success and low rates of complications by expert operators. In absence of available data from randomized trials, several observational studies have shown the benefits of CTO percutaneous coronary intervention (PCI) in insuring better cardiovascular outcome, particularly by improving ventricular function and reducing cardiac mortality. PMID- 26380784 TI - A meta-analysis of left atrial appendage closure for stroke prevention in atrial fibrillation-adding to the debate but elements remain unresolved. PMID- 26380785 TI - High flow on the rise-pediatric perspectives on the FLORALI trial. PMID- 26380786 TI - High flow nasal cannula-coming to a hypoxic patient near you! PMID- 26380787 TI - Surgical treatment of atrial fibrillation-what have we learned? PMID- 26380788 TI - Surgical ablation for atrial fibrillation: an editorial. PMID- 26380789 TI - Big-data Clinical Trial (BCT): the third talk. PMID- 26380790 TI - The air we breathe and lung disease. PMID- 26380791 TI - Electronic cigarettes: the new face of nicotine delivery and addiction. PMID- 26380792 TI - Spontaneous pneumothorax as the first manifestation of lung cancer: two case report. AB - Spontaneous pneumothorax (SP), as the first manifestation of lung cancer, is relatively rare, with reported occurrence rate of between 0.03% and 0.05%. The mechanism of concurrent pneumothorax with lung cancer is not clear, however several theories were proposed, including tumor necrosis mechanism and rupture of the bulla which contains tumor. We herein report two cases of lung cancer, in which the initial manifestations was only limited to SP. Without any radiologic abnormalities preoperatively, wedge resection of bullatous lung and subsequent histologic study followed. Pathologic study revealed the presence of bullatous change of the lung and combined lung cancer. PMID- 26380793 TI - A case of recurrent pneumothorax related to oral methylphenidate. AB - Primary spontaneous pneumothorax (PSP) commonly occurs in young, tall, and thin males, without any identifiable cause except for emphysema-like changes (ELCs). However, other risk factors may be overlooked. Herein, we report the case of a 19 year-old male who presented with recurrent spontaneous pneumothorax while taking oral methylphenidate. PMID- 26380794 TI - Precision medicine initiative-report of the 10th Lung Cancer Summit Forum for Chinese Directors of Thoracic Surgery and the 4th Summit Forum for Chinese Lung Cancer Collaborative Group (CLCCG). PMID- 26380795 TI - AME College: a Clinical Research Training Program. PMID- 26380796 TI - Prof. He Jianxing was granted AATS membership. PMID- 26380797 TI - Time to change: big show for revolution in the 8(th) National Forum on Minimally Invasive Surgery for Lung Cancer. PMID- 26380798 TI - Stress Among Iranian Nurses in Critical Wards. AB - BACKGROUND: Stress has been recognized as a significant psychosocial and physiologic component in educational and practical processes. OBJECTIVES: The purpose of present study was to survey stress among Iranian nurses in critical wards. PATIENTS AND METHODS: In this cross-sectional study, 3643 anonymous questionnaires were disseminated among nurses in different hospitals in Tehran, Iran, by utilizing multistage random sampling. The questionnaire consisted of two sections: demographic characteristics and a 22-item list on a five-point Likert scale. The association of variables with stress was evaluated using hierarchical logistic regression. RESULTS: A total of 3043 completed questionnaires were completed and returned (response rate, 83.53%). Age (> 33 years, 1571 (51.63%); < 33 years old, 1472 (48.37%)), marital status (single, 188 (6.18%); married, 2685 (88.24%); and widow, 170 (5.59%)), working shift (morning, 605 (19.88%); evening, 631 (20.74%); night, 603 (19.82%); and rotation, 1204 (39.57%)), and the years of experience of nurses (1 - 5 years, 413 (13.57%); 6 - 10 years, 589 (19.36%); 11 - 15 years, 832 (27.34%); 16 - 20 years, 758 (24.91%); and 21-25 years, 451 (14.82%)) had significant association with the level of stress (P < 0.05 for all parameters). However, sex (male, 937 (30.79%); and female, 2106 (69.21%)), education (associate, 444 (14.59%); baccalaureate, 2250 (73.94%); and master, 349 (11.47%)), and body mass index (> 24.6 kg/m(2), 2514 (49.75%); and < 24.6 kg/m(2), 1529 (50.25%)) showed no significant association with the level of stress (P > 0.05 for all parameters). CONCLUSIONS: Considering the personal and background characteristics of personnel and understanding their association with stress and stressful situations encompasses the ability to persevere and adapt to contextual stressors. PMID- 26380800 TI - Anatomy, feeding ecology, and ontogeny of a transitional baleen whale: a new genus and species of Eomysticetidae (Mammalia: Cetacea) from the Oligocene of New Zealand. AB - The Eocene history of cetacean evolution is now represented by the expansive fossil record of archaeocetes elucidating major morphofunctional shifts relating to the land to sea transition, but the change from archaeocetes to modern cetaceans is poorly established. New fossil material of the recently recognized family Eomysticetidae from the upper Oligocene Otekaike Limestone includes a new genus and species, Waharoa ruwhenua, represented by skulls and partial skeletons of an adult, juvenile, and a smaller juvenile. Ontogenetic status is confirmed by osteohistology of ribs. Waharoa ruwhenua is characterized by an elongate and narrow rostrum which retains vestigial alveoli and alveolar grooves. Palatal foramina and sulci are present only on the posterior half of the palate. The nasals are elongate, and the bony nares are positioned far anteriorly. Enormous temporal fossae are present adjacent to an elongate and narrow intertemporal region with a sharp sagittal crest. The earbones are characterized by retaining inner and outer posterior pedicles, lacking fused posterior processes, and retaining a separate accessory ossicle. Phylogenetic analysis supports inclusion of Waharoa ruwhenua within a monophyletic Eomysticetidae as the earliest diverging clade of toothless mysticetes. This eomysticetid clade also included Eomysticetus whitmorei, Micromysticetus rothauseni, Tohoraata raekohao, Tokarahia kauaeroa, Tokarahia lophocephalus, and Yamatocetus canaliculatus. Detailed study of ontogenetic change demonstrates postnatal elaboration of the sagittal and nuchal crests, elongation of the intertemporal region, inflation of the zygomatic processes, and an extreme proportional increase in rostral length. Tympanic bullae are nearly full sized during early postnatal ontogeny indicating precocial development of auditory structures, but do increase slightly in size. Positive allometry of the rostrum suggests an ontogenetic change in feeding ecology, from neonatal suckling to a more specialized adult feeding behaviour. Possible absence of baleen anteriorly, a delicate temporomandibular joint with probable synovial capsule, non-laterally deflected coronoid process, and anteroposteriorly expanded palate suggests skim feeding as likely mode of adult feeding for zooplankton. Isotopic data in concert with preservation of young juveniles suggests the continental shelf of Zealandia was an important calving ground for latitudinally migrating Oligocene baleen whales. PMID- 26380799 TI - Strained Dating Relationships, A Sense of Mattering and Emerging Adults' Depressive Symptoms. AB - Dating relationships become increasingly important as individuals transition into young adulthood. Such relationships often involve positive and negative interactions, which may have implications for psychological well-being. We analyzed data from the fourth interview of the Toledo Adolescent Relationships Study (TARS), when respondents were ages 18-24, to assess the influence of relationship dynamics on depressive symptoms. Using ordinary least squares regression models, among individuals currently dating (n=422), we first examined the influence of a sense of mattering as well as strained dynamics of dating relationships (e.g., communication awkwardness, conflict, sexual non-exclusivity and influence attempts) as correlates of depressive symptoms. Next, we tested whether these correlates differed for male and female daters. We found that a sense of mattering, communication awkwardness, conflict, sexual non-exclusivity and influence attempts were significant correlates of depressive symptoms. However, gender interactions were not significant suggesting that these same correlates were associated with depressive symptoms in a similar manner for both men and women in dating relationships. We also found that a sense of mattering mediated the relationship between conflict and depressive symptoms, and partially mediated the relationship between communication awkwardness, partner sexually non exclusivity and partner influence dynamics and depressive symptoms. This suggested that feeling that one matters is important in dating relationships and may reduce the risk of depressive symptoms. PMID- 26380801 TI - Attitudes towards suicide attempts broadcast on social media: an exploratory study of Chinese microblogs. AB - Introduction. Broadcasting a suicide attempt on social media has become a public health concern in many countries, particularly in China. In these cases, social media users are likely to be the first to witness the suicide attempt, and their attitudes may determine their likelihood of joining rescue efforts. This paper examines Chinese social media (Weibo) users' attitudes towards suicide attempts broadcast on Weibo. Methods. A total of 4,969 Weibo posts were selected from a customised Weibo User Pool which consisted of 1.06 million active users. The selected posts were then independently coded by two researchers using a coding framework that assessed: (a) Themes, (b) General attitudes, (c) Stigmatising attitudes, (d) Perceived motivations, and (e) Desired responses. Results and Discussion. More than one third of Weibo posts were coded as "stigmatising" (35%). Among these, 22%, 16%, and 15% of posts were coded as "deceitful," "pathetic," and "stupid," respectively. Among the posts which reflected different types of perceived motivations, 57% of posts were coded as "seeking attention." Among the posts which reflected desired responses, 37% were "not saving" and 28% were "encouraging suicide." Furthermore, among the posts with negative desired responses (i.e., "not saving" and "encouraging suicide"), 57% and 17% of them were related to different types of stigmatising attitudes and perceived motivations, respectively. Specifically, 29% and 26% of posts reflecting both stigmatising attitudes and negative desired responses were coded as "deceitful" and "pathetic," respectively, while 66% of posts reflecting both perceived motivations, and negative desired responses were coded as "seeking attention." Very few posts "promoted literacy" (2%) or "provided resources" (8%). Gender differences existed in multiple categories. Conclusions. This paper confirms the need for stigma reduction campaigns for Chinese social media users to improve their attitudes towards those who broadcast their suicide attempts on social media. Results of this study support the need for improved public health programs in China and may be insightful for other countries and other social media platforms. PMID- 26380802 TI - Positive Behavioral Interventions and Family Support for Fetal Alcohol Spectrum Disorders. AB - Although the scientific community has recognized the effects of prenatal alcohol exposure on development for over 40 years, the empirical study of positive behavioral interventions and family support programs for people with fetal alcohol spectrum disorders (FASD) has only just emerged over the last 10 to 15 years. In this time, dedicated researchers have developed innovative programs that have generally produced large effects and have been acceptable to children with FASD and their families. This body of work demonstrates that children with FASD can benefit from interventions that are appropriately tailored to their neurodevelopmental disabilities. Despite this progress, much work lies ahead to meet the significant needs of people with FASD. This review evaluates available sources of information, including theoretical and Lived Experience models, empirical evidence on existing programs, and best practice guidelines, to guide future research priorities and clinical practice. Three priorities for future intervention research are offered. PMID- 26380803 TI - Adult onset of ganglioneuroblastoma of the adrenal gland: case report and review of the literature. AB - Ganglioneuroblastoma (GBN) is a malignant neoplasm of the autonomic nervous system. Adult onset of ganglioneuroblastoma is extremely rare. Only 16 cases have been reported in English literature, to date. Surgery represents the first-line therapy for the treatment of ganglioneuroblastoma. Radiation therapy is indicated in patients with localized unresectable disease. Chemotherapy is reserved for metastatic disease. We present the case of a 63-year-old man affected by ganglioneuroblastoma of the adrenal gland. The diagnosis was made incidentally. The tumor, measuring 5 * 3 cm, was successfully surgically removed. PMID- 26380804 TI - A peripheral primitive neuroectodermal tumor originating from the pancreas: a case report and review of the literature. AB - A peripheral primitive neuroectodermal tumor (pPNET) is a small round cell tumor occurring mostly in children or young adults and categorized into the Ewing sarcoma family of tumors. pPNETs originating from the pancreas are especially rare, and only 25 cases have been reported in the literature. We report a case of a 22-year-old man who had a giant expansive tumor located in the uncinate process of the pancreas, 80 mm in diameter resulting in obstruction in the duodenum. The patient underwent a pancreaticoduodenectomy. The histological examination showed that the pancreatic tumor was composed of atypical small round cells. Immunohistochemical findings were positive for CD99. An Ewing sarcoma breakpoint region 1 gene 22q12 rearrangement was proven by a two-color fluorescence in situ hybridization assay. We diagnosed the tumor as a pPNET of the pancreas, which, according to the literature, is highly aggressive with poor prognosis. A multidisciplinary approach to treat these neoplasms should improve the prognoses. PMID- 26380805 TI - Adenomyoepithelioma of the breast coexisting with ductal carcinoma in situ: a case report and review of the literature. AB - We herein report a case of adenomyoepithelioma (AME) of the breast with ductal carcinoma in situ (DCIS) involving a 71-year-old Japanese woman. She presented with bloody discharge from the left nipple. Mammography and ultrasonography showed a well-defined polygonal tumor. Fine-needle aspiration cytology of the mass and stamp cytology of the bloody nipple discharge showed malignancy. Mastectomy and a sentinel lymph node biopsy were performed. The final diagnosis was AME of the breast with DCIS. There are no reports of AME of the breast presenting with bloody nipple discharge; upon a diagnosis of AME of the breast with bloody nipple discharge, the possibility of the coexistence of breast cancer should thus be considered when encountering such cases. PMID- 26380806 TI - Total colectomy for multiple metachronous colon cancers in a patient with Lynch syndrome. AB - Lynch syndrome (LS) is a disorder caused by mismatch repair gene mutations, which have been recognized to be associated with an increased frequency of colorectal and extracolorectal tumors. However, it remains controversial as to whether total or segmental colectomy should be performed to treat colorectal cancer in patients with LS. A 58-year-old male underwent total colectomy with ileostomy for advanced transverse colon cancer. He was also found to have LS based on his characteristic family history and the findings of a preoperative examination, including a microsatellite instability analysis of past multiple metachronous cancers. The postoperative histological findings showed mucinous adenocarcinoma without lymph node metastasis, and the loss of the MSH2 protein expression was confirmed on an immunohistochemical examination. The present case provided important information on the clinical management of multiple developing metachronous colorectal cancers in patients with LS. PMID- 26380807 TI - Ultra-Marathon Athletes at Risk for the Female Athlete Triad. AB - BACKGROUND: Worldwide female participation in ultra-endurance events may place them at risk for the female athlete triad (FAT). The study objectives were to establish triad knowledge, occurrence of disordered eating and triad risk amongst participants of the 2014 89-km Comrades Marathon event. METHODS: A survey utilising the Low Energy Availability in Females questionnaire (LEAF-Q) and Female Athlete Screening Tool (FAST) questionnaire was conducted on female participants in order to determine the risk. In addition, seven questions pertaining to the triad were asked in order to determine the athlete's knowledge of the triad. Athletes were requested to complete the anonymous questionnaire after written informed consent was obtained while waiting in the event registration queues. Statistical analyses included Pearson product-moment correlations, chi-square tests and cross-tabulations to evaluate associations of interest. RESULTS: Knowledge of the triad was poor with 92.5 % of participants having not heard of the triad before and most of those who had, gained their knowledge from school or university. Only three athletes were able to name all 3 components of the triad. Amenorrhoea was the most commonly recalled component while five participants were able to name the component of low bone mineral density. Of the 306 athletes included in the study, 44.1 % were found to be at risk for the female athlete triad. One-third of participants demonstrated disordered eating behaviours with nearly half reporting restrictive eating behaviours. There is a significant association between athletes at risk for the triad according to the LEAF-Q and those with disordered eating (chi2(1) = 8.411, p = 0.014) but no association (or interaction) between triad knowledge and category (at risk/not at risk) of LEAF-Q score (chi2(1) = 0.004, p = 0.949). More athletes in the groups with clinical and sub-clinical eating disorders are at risk for the triad than expected under the null hypothesis for no association. CONCLUSIONS: Only 7.5 % of the female Comrades Marathon runners knew about the triad despite 44.1 % being at a high risk for the triad. Therefore, education and regular screening programmes targeting these athletes are overdue. Postmenopausal athletes are at particularly high risk for large losses in bone mass if they experience chronic energy deficiency and hence require special focus. PMID- 26380808 TI - Bioimaging of microRNA124a-independent neuronal differentiation of human G2 neural stem cells. AB - Evaluation of the function of microRNAs (miRNAs or miRs) through miRNA expression profiles during neuronal differentiation plays a critical role not only in identifying unique miRNAs relevant to cellular development but also in understanding regulatory functions of the cell-specific miRNAs in living organisms. Here, we examined the microarray-based miRNA expression profiles of G2 cells (recently developed human neural stem cells) and monitored the expression pattern of known neuron-specific miR-9 and miR-124a during neuronal differentiation of G2 cells in vitro and in vivo. Of 500 miRNAs analyzed by microarray of G2 cells, the expression of 90 miRNAs was significantly increased during doxycycline-dependent neuronal differentiation of G2 cells and about 60 miRNAs showed a gradual enhancement of gene expression as neuronal differentiation progressed. Real-time PCR showed that expression of endogenous mature miR-9 was continuously and gradually increased in a pattern dependent on the period of neuronal differentiation of G2 cells while the increased expression of neuron-specific mature miR-124a was barely observed during neurogenesis. Our recently developed miRNA reporter imaging vectors (CMV/Gluc/3*PT_miR-9 and CMV/Gluc/3*PT_miR-124a) containing Gaussia luciferase, CMV promoter and three copies of complementary nucleotides of each corresponding miRNA showed that luciferase activity from CMV/Gluc/3*PT_miR-9 was gradually decreased both in vitro and in vivo in G2 cells induced to differentiate into neurons. However, in vitro and in vivo bioluminescence signals for CMV/Gluc/3*PT_miR-124a were not significantly different between undifferentiated and differentiated G2 cells. Our results demonstrate that biogenesis of neuron-specific miR-124a is not necessary for doxycycline-dependent neurogenesis of G2 cells. PMID- 26380809 TI - Activation of Notch3 promotes pulmonary arterial smooth muscle cells proliferation via Hes1/p27Kip1 signaling pathway. AB - Activation of the Notch3 cascade is involved in the development of pulmonary arterial hypertension by stimulating the proliferation of vascular smooth muscle cells. However, the detailed molecular mechanisms underlying this effect are still unclear. The present study aims to address this issue. We demonstrated that over-expression of intracellular domain of the Notch3 receptor (NICD3) by adenovirus transfection dramatically induced proliferation of primary cultured pulmonary artery smooth muscle cells. This was accompanied with up-regulation of Hes1 protein and down-regulation of p27Kip1 protein. More importantly, we observed that prior silencing of Hes1 with siRNA blocked NICD3 over-expression induced p27Kip1 reduction and cell proliferation. The present study suggests that Hes1 lies downstream of NICD3 and particularly mediates Notch3 signaling-induced proliferation of pulmonary arterial smooth muscle cells by down-regulation of p27Kip1 expression. PMID- 26380810 TI - A new high-resolution crystal structure of the Drosophila melanogaster angiotensin converting enzyme homologue, AnCE. AB - Angiotensin converting enzyme (ACE) is a zinc-dependent dipeptidyl carboxypeptidase with an essential role in blood pressure homeostasis in mammals. ACE has long been targeted in the treatment of hypertension through ACE inhibitors, however current inhibitors are known to cause severe side effects. Therefore, there is a requirement for a new generation of ACE inhibitors and structural information will be invaluable in their development. ACE is a challenging enzyme to work with due to its extensive glycosylation. As such, the Drosophila melanogaster ACE homologue, AnCE, which shares ~60% sequence similarity with human ACE, can be used as a model for studying inhibitor binding. The presence of ligands originating from the crystallisation condition at the AnCE active site has proved an obstacle to studying the binding of new inhibitor precursors. Here we present the crystal structure of AnCE (in a new crystal form) at 1.85 A resolution, using crystals grown under different conditions. This new structure may be more suitable for studying the binding of new compounds, with the potential of developing a new generation of improved ACE inhibitors. PMID- 26380811 TI - NDRG2 promotes myoblast proliferation and caspase 3/7 activities during differentiation, and attenuates hydrogen peroxide - But not palmitate-induced toxicity. AB - The function of the stress-responsive N-myc downstream-regulated gene 2 (NDRG2) in the control of myoblast growth, and the amino acids contributing to its function, are not well characterized. Here, we investigated the effect of increased NDRG2 levels on the proliferation, differentiation and apoptosis in skeletal muscle cells under basal and stress conditions. NDRG2 overexpression increased C2C12 myoblast proliferation and the expression of positive cell cycle regulators, cdk2, cyclin B and cyclin D, and phosphorylation of Rb, while the serine/threonine-deficient NDRG2, 3A-NDRG2, had less effect. The onset of differentiation was enhanced by NDRG2 as determined through the myogenic regulatory factor expression profiles and myocyte fusion index. However, the overall level of differentiation in myotubes was not different. While NDRG2 up regulated caspase 3/7 activities during differentiation, no increase in apoptosis was measured by TUNEL assay or through cleavage of caspase 3 and PARP proteins. During H2O2 treatment to induce oxidative stress, NDRG2 helped protect against the loss of proliferation and ER stress as measured by GRP78 expression with 3A NDRG2 displaying less protection. NDRG2 also attenuated apoptosis by reducing cleavage of PARP and caspase 3 and expression of pro-apoptotic Bax while enhancing the pro-survival Bcl-2 and Bcl-xL levels. In contrast, Mcl-1 was not altered, and NDRG2 did not protect against palmitate-induced lipotoxicity. Our findings show that NDRG2 overexpression increases myoblast proliferation and caspase 3/7 activities without increasing overall differentiation. Furthermore, NDRG2 attenuates H2O2-induced oxidative stress and specific serine and threonine amino acid residues appear to contribute to its function in muscle cells. PMID- 26380812 TI - Pre-operative lymphocyte-to-monocyte ratio as a predictor of overall survival in patients suffering from osteosarcoma. AB - Inflammatory markers have been proposed to predict clinical outcomes in many types of cancers. The purpose of this study was to explore the influence of the lymphocyte-to-monocyte ratio (LMR) on clinical prognosis of patients with osteosarcoma. This study collected 327 patients who underwent surgical treatment for osteosarcoma during the period 2006-2010. LMR was calculated from pre operative peripheral blood cells counts. The optimal cut-off value of LMR was determined based on receiver operating characteristic curve analysis. Overall survival (OS) and event free survival (EFS) was plotted using the Kaplan-Meier method and evaluated by the log-rank test. A predictive model was established to predict clinical prognosis for OS, and the predictive accuracy of this model was determined by concordance index (c-index). Our results showed that young age, elevated alkaline phosphatase, metastasis at diagnosis, chemotherapy, lymphocyte and monocyte counts were significantly associated with LMR. Low LMR was associated with shorter OS and EFS (P < 0.001), and was an independent predictor of both OS and EFS (HR = 1.72, 95% CI = 1.14-2.60, P = 0.010; HR = 1.89, 95% CI = 1.32-2.57, P = 0.009). The nomogram performed well in the prediction of overall survival in patients with osteosarcoma (c-index 0.630). In conclusion, low pre operative LMR is associated with a poor prognosis in patients suffering from osteosarcoma. A prospective study is warranted for further validation of our results. PMID- 26380813 TI - GIT2 deficiency attenuates concanavalin A-induced hepatitis in mice. AB - G protein-coupled receptor kinase interactor 2 (GIT2) is a signaling scaffold protein involved in regulation of cytoskeletal dynamics and the internalization of G protein-coupled receptors (GPCRs). The short-splice form of GIT2 is expressed in peripheral T cells and thymocytes. However, the functions of GIT2 in T cells have not yet been determined. We show that treatment with Con A in a model of polyclonal T-lymphocyte activation resulted in marked inhibitions in the intrahepatic infiltration of inflammatory cells, cytokine response and acute liver failure in Git2 (-/-) mice. CD4(+) T cells from Git2 (-/-) mice showed significant impairment in proliferation, cytokine production and signal transduction upon TCR-stimulated activation. Our results suggested that GIT2 plays an important role in T-cell function in vivo and in vitro. PMID- 26380814 TI - Association of the NAD(P)H oxidase p22 phox gene C242T polymorphism with type 2 diabetes mellitus, diabetic nephropathy, and carotid atherosclerosis with type 2 diabetes mellitus: A meta-analysis. AB - BACKGROUND: Several epidemiological studies have evaluated the association between the NAD(P)H oxidase p22 phox gene C242T polymorphism and the risk of type 2 diabetes mellitus (T2DM), diabetic nephropathy (DN), and carotid atherosclerosis with T2DM (CA), but the results are inconclusive. This meta analysis was therefore designed to clarify these controversies. METHODS: Systematic searches were performed using electronic databases such as MEDLINE, PubMed, EMBASE, and China National Knowledge Infrastructure, as well as through manual searching of the references of identified articles. A total of 11 publications were eligible for this meta-analysis after running a search on the NAD(P)H oxidase p22 phox gene C242T polymorphism, including 7 with outcomes for T2DM, 7 with outcomes for DN, and 3 with outcomes for CA. The pooled odds ratio (OR) with a 95% confidence interval (CI) was calculated using a fixed effects model (FEM) or a random effects model (REM). Publication bias was tested by Begg's funnel plot analysis. Sensitivity analysis was also performed. RESULTS: The results showed a significant association between the NAD(P)H oxidase p22 phox gene C242T polymorphism and T2DM risk in the allelic model (REM: OR = 1.23, 95% CI = 1.06-1.43), additive model (FEM: OR = 1.61, 95% CI = 1.14-2.26), and recessive model (FEM: OR = 1.50, 95% CI = 1.10-2.05). A significant association was also observed for DN in the allelic model (REM: OR = 1.25, 95% CI = 1.06 1.47), additive model (FEM: OR = 1.61, 95% CI = 1.08-2.38), and dominant model (REM: OR = 1.26, 95% CI = 1.03-1.54). However, no association was observed for CA. Similar results were obtained in subgroup analysis based on ethnicity. CONCLUSIONS: Results of this meta-analysis suggest that the NAD(P)H oxidase p22 phox gene 242T allele might be associated with an increased risk of T2DM and DN, but not CA. PMID- 26380815 TI - Association between pro-(IL-8) and anti-inflammatory (IL-10) cytokine variants and their serum levels and H. pylori-related gastric carcinogenesis in northern India. AB - BACKGROUND: Interleukin (IL)-8 -251 T/A and IL-10 (-1082 G/A and -819/592 C/T) polymorphisms and their expression may influence gastritis, atrophy, intestinal metaplasia (IM) and gastric cancer (GC) following H. pylori infection. METHODS: Genotyping of these genes was performed (ASO-PCR) in 200, 182 and 250 with GC, functional dyspepsia (FD) and healthy controls (HC), respectively. Anti-H. pylori IgG-antibody was tested in all and serums IL-8 and IL-10 were measured randomly in 60 subjects of each group by ELISA. RESULTS: Pro-(IL-8)-251 AA and anti inflammatory (IL-10)-819 TT genotypes were commoner among GC than HC (p = 0.023, OR 1.86 [1.09-3.2] and p = 0.020, OR 2.0 [1.11-3.5]) but comparable with FD. IL-8 AA and IL-10-819 T allele carriage was also commoner in H. pylori-infected GC than HC (p = 0.011, OR 2.47 [1.23-5.0], and p = 0.018, OR 2.3 (1.16-4.59). IL-10 1082 G/A genotype and haplotypes (ACC, GCC, ATA and GTA) were comparable in all groups. Circulating levels of IL-8 and IL-10 were higher among GC than HC but comparable to FD (IL-8; 57.64 [6.44-319.46] vs. 54.35 [4.24-318.96] and 26.33 [4.67-304.54] pg/ml, p < 0.001 and IL-10; 15.47 [1.01-270.87] vs. 12.28 [0.96 64.88] and 3.79 [1.24-56.65], p < 0.001 for GC vs. HC). IL-8/IL-10 ratio was lower among GC than HC but higher than FD (3.7 [0.18-38.41] vs. 6.59 [0.98 130.2], p < 0.001 and 4.22 [0.15-61.4], p < 0.01). Circulating levels of IL-8, IL 10 and IL-8/lL-10 ratios were different among H. pylori-infected and non-infected GC than HC (p < 0.001, p < 0.001 and p < 0.01). CONCLUSIONS: Pro-(IL-8)-251 T/A and anti-inflammatory (IL-10)-819 C/T gene polymorphisms and their circulating levels may play a role in H. pylori-associated gastric carcinogenesis in northern India. PMID- 26380817 TI - Correction. AB - [This corrects the article DOI: 10.7860/JCDR/2013/5704.3613.]. PMID- 26380818 TI - Correction. AB - [This corrects the article DOI: 10.7860/JCDR/2014/8481.5063.]. PMID- 26380816 TI - Expression profile of six stress-related genes and productive performances of fast and slow growing broiler strains reared under heat stress conditions. AB - High temperature is one of the prominent environmental factors causing economic losses to the poultry industry as it negatively affects growth and production performance in broiler chickens. We used One Step TaqMan real time RT-PCR (reverse transcription polymerase chain reaction) technology to study the effects of chronic heat stress on the expression of genes codifying for the antioxidative enzymes superoxide dismutase (SOD), and catalase (CAT), as well as for heat shock protein (HSP) 70, HSP90, glucocorticoid receptor (NR3C1), and caspase 6 (CASP6) in the liver of two different broiler genetic strains: Red JA Cou Nu Hubbard (CN) and Ross 508 Aviagen (RO). CN is a naked neck slow growing broiler intended for the free range and/or organic markets, whereas RO is selected for fast growing. We also analysed the effect of chronic heat stress on productive performances, and plasma corticosterone levels as well as the association between transcriptomic response and specific SNPs (single nucleotide polymorphisms) in each genetic strain of broiler chickens. RO and CN broilers, 4 weeks of age, were maintained for 4 weeks at either 34 degrees C or 22 degrees C. The results demonstrated that there was a genotype and a temperature main effect on the broilers' growth from the 4th to the 8th week of age, but the interaction effect between genotype and temperature resulted not statistically significant. By considering the genotype effect, fast growing broilers (RO) grew more than the slow growing ones (CN), whereas by considering the temperature effect, broilers in unheated conditions grew more than the heat stressed ones. Corticosterone levels increased significantly in the blood of heat stressed broilers, due to the activation of the HPA (hypothalamic-pituitary-adrenocortical axis). Carcass yield at slaughter was of similar values in the 4 cohorts (genotype/temperature combinations or treatment groups), ranging from 86.5 to 88.6%, whereas carcass weight was negatively influenced by heat stress in both broiler strains. Heat stress affected gene expression by downregulating CASP6 and upregulating CAT transcript levels. HSPs, SOD and NR3C1 mRNA levels remained unaffected by heat stress. The differences found in the mRNA copies of CASP6 gene could be partly explained by SNPs. PMID- 26380819 TI - Association Between Epicardial Fat Thickness and Premature Coronary Artery Disease: A Case Control Study. AB - BACKGROUND: The association between epicardial fat thickness (EFT) and premature coronary artery disease (CAD) has not been elaborately studied. OBJECTIVES: In the present study, we sought whether such a relationship between EFT and CAD exists. PATIENTS AND METHODS: Sixty two consecutive subjects, under 50 years of age, who underwent coronary angiography (CAG) with the aspect of CAD, were included in this case control study. They were divided into two groups of 31 subjects, namely CAD (cases) and non-CAD (controls) group, according to CAG data. Presence of conventional coronary risk factors, drug history, and anthropometric data were recorded. Then, each subject underwent standard transthoracic echocardiography for measuring EFT in the proximal part of right ventricular outflow tract in the parasternal long axis view at end diastole, as well as other parameters of systolic and diastolic function, and left ventricle (LV) mass. Images were stored for offline analysis when the echocardiocardiographers were blind to CAG data. RESULTS: Among baseline characteristics, waist circumference, triglyceride levels, cigarette smoking and history of statin use were significantly higher in the CAD group. The body mass index (BMI) was significantly higher in the non-CAD group. According to echocardiographic data, the EFT with a cut off value of 2.95 mm could well differentiate subjects in each group. The LV mass and E/e were significantly higher in CAD group, in addition to EFT. Also, there was a significant correlation between EFT and waist circumference, as well as LV mass. However, no significant relation was between EFT and LV systolic and diastolic function. CONCLUSIONS: The EFT, as measured by echocardiography, with a cut off value 2.95 mm has a strong association with premature CAD. PMID- 26380820 TI - Unusual Presentation of Melioidosis in a Case of Pseudoaneurysm of Descending Thoracic Aorta: Review of Two Case Reports. AB - INTRODUCTION: Melioidosis is a rapidly fatal infectious disease caused by Burkholderia pseudomallei, an agent of potential biothreat, endemic in several parts of India. Most melioidosis-induced infected aneurysms are located in the abdominal or thoracic aorta. CASE PRESENTATION: We reported two unusual cases of melioidosis resulting in pseudoaneurysm of the descending thoracic aorta. In both cases, blood cultures yielded B. pseudomallei. The first patient was managed with resection of aneurysm and reconstruction with Dacron graft followed by medical treatment and was discharged uneventfully. The second patient died within one week of admission before the infecting etiological agent was identified and aneurysmal repair was planned. CONCLUSIONS: A high clinical index of suspicion, especially in areas of endemicity is essential for timely management of intracavitary infected pseudoaneurysms caused by B. pseudomallei and use of rapid microbiological techniques, such as bact/alert 3D system, which enables rapid and early recovery of the etiological agent. PMID- 26380821 TI - Characterization of a Novel Mutation in SLC1A1 Associated with Schizophrenia. AB - We have recently described a hemi-deletion on chromosome 9p24.2 at the SLC1A1 gene locus and its co-segregation with schizophrenia in an extended Palauan pedigree. This finding represents a point of convergence for several pathophysiological models of schizophrenia. The present report sought to characterize the biological consequences of this hemi-deletion. Dual luciferase assays demonstrated that the partially deleted allele (lacking exon 1 and the native promoter) can drive expression of a 5'-truncated SLC1A1 using sequence upstream of exon 2 as a surrogate promoter. However, confocal microscopy and electrophysiological recordings demonstrate that the 5'-truncated SLC1A1 lacks normal membrane localization and glutamate transport ability. To identify downstream consequences of the hemi-deletion, we first used a themed qRT-PCR array to compare expression of 84 GABA and glutamate genes in RNA from peripheral blood leukocytes in deletion carriers (n = 11) versus noncarriers (n = 8) as well as deletion carriers with psychosis (n = 5) versus those without (n = 3). Then, targeted RNA-Seq (TREx) was used to quantify expression of 375 genes associated with neuropsychiatric disorders in HEK293 cells subjected to either knockdown of SLC1A1 or overexpression of full-length or 5'-truncated SLC1A1. Expression changes of several genes strongly implicated in schizophrenia pathophysiology were detected (e.g. SLC1A2, SLC1A3, SLC1A6, SLC7A11, GRIN2A, GRIA1 and DLX1). PMID- 26380823 TI - Intraoperative neurophysiological monitoring in spinal surgery. AB - Recently, many surgeons have been using intraoperative neurophysiological monitoring (IOM) in spinal surgery to reduce the incidence of postoperative neurological complications, including level of the spinal cord, cauda equina and nerve root. Several established technologies are available and combined motor and somatosensory evoked potentials are considered mandatory for practical and successful IOM. Spinal cord evoked potentials are elicited compound potentials recorded over the spinal cord. Electrical stimulation is provoked on the dorsal spinal cord from an epidural electrode. Somatosensory evoked potentials assess the functional integrity of sensory pathways from the peripheral nerve through the dorsal column and to the sensory cortex. For identification of the physiological midline, the dorsal column mapping technique can be used. It is helpful for reducing the postoperative morbidity associated with dorsal column dysfunction when distortion of the normal spinal cord anatomy caused by an intramedullary cord lesion results in confusion in localizing the midline for the myelotomy. Motor evoked potentials (MEPs) consist of spinal, neurogenic and muscle MEPs. MEPs allow selective and specific assessment of the functional integrity of descending motor pathways, from the motor cortex to peripheral muscles. Spinal surgeons should understand the concept of the monitoring techniques and interpret monitoring records adequately to use IOM for the decision making during the surgery for safe surgery and a favorable surgical outcome. PMID- 26380822 TI - Vitamin K and hepatocellular carcinoma: The basic and clinic. AB - Vitamin K (VK), which was originally identified as a cofactor involved in the production of functional coagulation factors in the liver, has been shown to be involved in various aspects of physiological and pathological events, including bone metabolism, cardiovascular diseases and tumor biology. The mechanisms and roles of VK are gradually becoming clear. Several novel enzymes involved in the VK cycle were identified and have been shown to be linked to tumorigenesis. The VKs have been shown to suppress liver cancer cell growth through multiple signaling pathways via the transcription factors and protein kinases. A VK2 analog was applied to the chemoprevention of hepatocellular carcinoma (HCC) recurrence after curative therapy and was shown to have beneficial effects, both in the suppression of HCC recurrence and in patient survival. Although a large scale randomized control study failed to demonstrate the suppression of HCC recurrence, a meta-analysis suggested a beneficial effect on the long-term survival of HCC patients. However, the beneficial effects of VK administration alone were not sufficient to prevent or treat HCC in clinical settings. Thus its combination with other anti-cancer reagents and the development of more potent novel VK derivatives are the focus of ongoing research which seeks to achieve satisfactory therapeutic effects against HCC. PMID- 26380824 TI - Esthesioneuroblastoma: Multimodal management and review of literature. AB - Esthesioneuroblastoma (ENB) is a rare malignant neoplasm arising from the olfactory neuroepithelium. ENB constitutes only 3% of all malignant intranasal neoplasm. Because of the rarity, the number of patients of ENB treated in individual departments is small. Most of these patients presents in locally advanced stages and require multimodality treatment in form of surgery, chemotherapy and radiotherapy. Multimodality approach with a risk-adapted strategy is required to achieve good control rates while minimizing treatment related toxicity. PMID- 26380825 TI - Gingival enlargements: Differential diagnosis and review of literature. AB - Gingival enlargement is one of the frequent features of gingival diseases. However due to their varied presentations, the diagnosis of these entities becomes challenging for the clinician. They can be categorized based on their etiopathogenesis, location, size, extent, etc. Based on the existing knowledge and clinical experience, a differential diagnosis can be formulated. Subsequently, after detailed investigation, clinician makes a final diagnosis or diagnosis of exclusion. A perfect diagnosis is critically important, since the management of these lesions and prevention of their recurrence is completely dependent on it. Furthermore, in some cases where gingival enlargement could be the primary sign of potentially lethal systemic diseases, a correct diagnosis of these enlargements could prove life saving for the patient or at least initiate early treatment and improve the quality of life. The purpose of this review article is to highlight significant findings of different types of gingival enlargement which would help clinician to differentiate between them. A detailed decision tree is also designed for the practitioners, which will help them arrive at a diagnosis in a systematic manner. There still could be some lesions which may present in an unusual manner and make the diagnosis challenging. By knowing the existence of common and rare presentations of gingival enlargement, one can keep a broad view when formulating a differential diagnosis of localized (isolated, discrete, regional) or generalized gingival enlargement. PMID- 26380826 TI - Current trends in laparoscopic groin hernia repair: A review. AB - Hernia is a common problem of the modern world with its incidence more in developing countries. Inguinal hernia is the most common groin hernia repaired worldwide. With advancement in technology operative techniques of repair have also evolved. A PubMed and COCHRANE database search was accomplished in this regard to establish the current status of laparoscopic inguinal hernia repair in view of recent published literature. Published literature support that laparoscopic hernia repair is best suited for recurrent and bilateral inguinal hernia although it may be offered for primary inguinal hernia if expertise is available. PMID- 26380827 TI - Leukocyte function-associated antigen-1 deficiency impairs responses to polymicrobial sepsis. AB - AIM: To determine the role of leukocyte function-associated antigen-1 (LFA-1) in polymicrobial sepsis model in mice. METHODS: Cecal ligation and puncture model was used to study polymicrobial sepsis in wild type and LFA-1 knockout (KO) (= CD11a KO) mice. Their survivals were examined. Neutrophil recruitment to the abdominal cavity, bacterial tissue load and bacterial killing by neutrophils, tissue cytokine profiles, and serum cytokines were examined. Apoptosis of tissues was assessed using cleaved-caspase 3 and TUNNEL staining. The recruitment of neutrophils to various tissues was assessed using myeloperoxidase staining or measuring myeloperoxidase activity. RESULTS: LFA-1 deficiency significantly decreased survival (P = 0.0024) with the reduction of neutrophil recruitment to the abdominal cavity and higher bacterial load in blood. It was also associated with increased apoptosis in spleen and more organ injuries probed by interleukin 6 mRNA level. However, the deficiency of LFA-1 did not prevent neutrophil recruitment to lung, liver, spleen or kidney, which suggested the existence of LFA-1 independent recruitment mechanism in these organs. CONCLUSION: LFA-1 deficiency did not attenuate neutrophil recruitment to various organs to adequately mitigate secondary tissue injury in sepsis. It was associated with decreased neutrophil recruitment to the abdominal cavity, higher bacterial load, leading to increased mortality in an abdominal, polymicrobial sepsis. PMID- 26380830 TI - Coumadin ridge: An incidental finding of a left atrial pseudotumor on transthoracic echocardiography. AB - Coumadin ridge is a normal anatomic variant that is occasionally found in the left atrium. It can present as a linear or nodular mass which can undulate with cardiac motion and if particularly prominent, can easily be mistaken for a tumor or thrombus. Careful evaluation and consideration of the common variants discussed in this review can help limit misdiagnosis, as well as unnecessary workup and treatment. We present a case of coumadin ridge that was found on a patient using two-dimensional transthoracic echocardiography. PMID- 26380829 TI - Sports hernia and femoroacetabular impingement in athletes: A systematic review. AB - AIM: To investigate the association between sports hernias and femoroacetabular impingement (FAI) in athletes. METHODS: PubMed, MEDLINE, CINAHL, Embase, Cochrane Controlled Trials Register, and Google Scholar databases were electronically searched for articles relating to sports hernia, athletic pubalgia, groin pain, long-standing adductor-related groin pain, Gilmore groin, adductor pain syndrome, and FAI. The initial search identified 196 studies, of which only articles reporting on the association of sports hernia and FAI or laparoscopic treatment of sports hernia were selected for systematic review. Finally, 24 studies were reviewed to evaluate the prevalence of FAI in cases of sports hernia and examine treatment outcomes and evidence for a common underlying pathogenic mechanism. RESULTS: FAI has been reported in as few as 12% to as high as 94% of patients with sports hernias, athletic pubalgia or adductor-related groin pain. Cam-type impingement is proposed to lead to increased symphyseal motion with overload on the surrounding extra-articular structures and muscle, which can result in the development of sports hernia and athletic pubalgia. Laparoscopic repair of sports hernias, via either the transabdominal preperitoneal or extraperitoneal approach, has a high success rate and earlier recovery of full sports activity compared to open surgery or conservative treatment. For patients with FAI and sports hernia, the surgical management of both pathologies is more effective than sports pubalgia treatment or hip arthroscopy alone (89% vs 33% of cases). As sports hernias and FAI are typically treated by general and orthopedic surgeons, respectively, a multidisciplinary approach for diagnosis and treatment is recommended for optimal treatment of patients with these injuries. CONCLUSION: The restriction in range of motion due to FAI likely contributes to sports hernias; therefore, surgical treatment of both pathologies represents an optimal therapy. PMID- 26380828 TI - Role of genetic polymorphisms in hepatitis C virus chronic infection. AB - AIM: To analyze the host genetics factors influencing the clinical course and the response to antiviral treatment in patients with chronic hepatitis C (CHC). METHODS: We conducted an electronic search on the PubMed and MEDLINE (2000-2014) databases and Cochrane library (2000-2014). A total of 73 articles were retrieved and their data were extensively evaluated and discussed by the authors and then analyzed in this review article. RESULTS: Several studies associated polymorphisms in the interleukin 28B gene on chromosome 19 (19q13.13) with a spontaneous viral clearance in acute hepatitis C and with the response to pegylated interferon (Peg-IFN)-based treatment in chronic hepatitis C patients. Other investigations demonstrated that inosine triphosphate pyrophosphatase genetic variants protect hepatitis C virus-genotype-1 CHC patients from ribavirin induced anemia, and other studies that a polymorphism in the patatin-like phospholipase domain-containing protein 3 was associated with hepatic steatosis in CHC patients. Although not conclusive, some investigations suggested that the vitamin D-associated polymorphisms play an important role in the achievement of sustained virologic response in CHC patients treated with Peg-IFN-based antiviral therapy. Several other polymorphisms have been investigated to ascertain their possible impact on the natural history and on the response to treatment in patients with CHC, but the data are preliminary and warrant confirmation. CONCLUSION: Several genetic polymorphisms seem to influence the clinical course and the response to antiviral treatment in patients with CHC, suggesting individualized follow up and treatment strategies. PMID- 26380831 TI - Transhepatic venous approach to permanent pacemaker placement in a patient with limited central venous access. AB - The end-stage renal disease population poses a challenge for obtaining venous access required for life-saving invasive cardiac procedures. In this case report, we describe an adult patient with end-stage renal disease in whom the hepatic vein was the only available access to implant a single-lead permanent cardiac pacemaker. A 63-year-old male with end-stage renal disease on maintenance hemodialysis and permanent atrial fibrillation/atrial flutter presented with symptomatic bradycardia. Imaging studies revealed all traditional central venous access sites to be occluded/non-accessible. With the assistance of vascular interventional radiology, a trans-hepatic venous catheter was placed. This was then used to place a right ventricular pacing lead with close attention to numerous technical aspects. The procedure was completed successfully with placement of a single-lead permanent cardiac pacemaker. PMID- 26380832 TI - Horseshoe thrombus in a patient with mechanical prosthetic mitral valve: A case report and review of literature. AB - Patients with prosthetic cardiac valves are at high risk for thromboembolic complications and need life long anticoagulation with warfarin, which can be associated with variable dose requirements and fluctuating level of systemic anticoagulation and may predispose to thromboembolic and or hemorrhagic complications. Prosthetic cardiac valve thrombosis is associated with high morbidity and mortality. A high index of suspicion is essential for prompt diagnosis. Transthoracic echocardiography, and if required transesophageal echocardiography are the main diagnostic imaging modalities. Medically stable patients can be managed with thrombolytic therapy and anticoagulation, while some patients may require surgical thrombectomy or valve replacement. We present a case report of a patient with prosthetic mitral valve and an unusually large left atrial thrombus with both thromboembolic and hemorrhagic complications. PMID- 26380833 TI - Do inhaled corticosteroids increase the risk of Pneumocystis pneumonia in people with lung cancer? AB - Pneumocystis pneumonia (PCP) is a life-threatening infection in immunocompromised patients. It is relatively uncommon in patients with lung cancer. We report a case of PCP in a 59-year-old man with a past medical history of chronic obstructive pulmonary disease treated with formoterol and a moderate daily dose of inhaled budesonide. He had also advanced stage non-small lung cancer treated with concurrent chemo-radiation with a cisplatin-etoposide containing regimen. The diagnosis of PCP was suspected based on the context of rapidly increasing dyspnea, lymphopenia and the imaging findings. Polymerase chain reaction testing on an induced sputum specimen was positive for Pneumocystis jirovecii. The patient was treated with oral trimethoprim-sulfamethoxazole and systemic corticotherapy and had showed clinical and radiological improvement. Six months after the PCP diagnosis, he developed a malignant pleural effusion and expired on hospice care. Through this case, we remind the importance of screening for PCP in lung cancer patients under chemotherapeutic regimens and with increasing dyspnea. In addition, we alert to the fact that long-term inhaled corticosteroids may be a risk factor for PCP in patients with lung cancer. Despite intensive treatment, the mortality of PCP remains high, hence the importance of chemoprophylaxis should be considered. PMID- 26380834 TI - Perianal tuberculosis: A case report and review of the literature. AB - Tuberculosis (TB) is still a major health problem worldwide. We present a rare case of an immuno-competent patient with perianal TB. A 38-year-old man visited a clinic with pain, swelling, and redness in the perineum. He had been persistently coughing for the past 6 mo. The abscess had formed a fistula to the perianal region, indicating perianal abscess. Mycobacterium tuberculosis was found in sputum and perianal abscess. Surgical drainage was performed, and oral anti tuberculous drugs were administered for 6 mo. The patient's clinical course was favorable. On review of the literature on 58 cases of perianal TB, we found that the duration of persistent perianal lesion was much longer in patients without active pulmonary TB (APTB) than in those with APTB (66.4 mo vs 8.3 mo; confidence interval, 0.0760-0.9620, P = 0.0380). Thus, in cases of non-healing or recurrent perianal lesions, TB should be considered. PMID- 26380836 TI - The Conditions under which Growth-Fostering Relationships Promote Resilience and Alleviate Psychological Distress among Sexual Minorities: Applications of Relational Cultural Theory. AB - Relational cultural theory posits that resilience and psychological growth are rooted in relational connections and are facilitated through growth-fostering relationships. Framed within this theory, the current study examined the associations between growth-fostering relationships (i.e., relationships characterized by authenticity and mutuality) with a close friend and psychological distress among sexual minorities. More specifically, we tested the moderating effects of individuals' internalized homophobia and their friend's sexual orientation on the associations between growth-fostering relationship with their close friend and level of psychological distress. A sample of sexual minorities (N = 661) were recruited online and completed a questionnaire. The 3 way interaction between (a) growth-fostering relationship with a close friend, (b) the close friend's sexual orientation, and (c) internalized homophobia was significant in predicting psychological distress. Among participants with low levels of internalized homophobia, a stronger growth-fostering relationship with a close heterosexual or LGBT friend was associated with less psychological distress. Among participants with high levels of internalized homophobia, a stronger growth-fostering relationship with a close LGBT friend was associated with less psychological distress but not with a heterosexual friend. Our results demonstrate that growth-fostering relationships may be associated with less psychological distress but under specific conditions. These findings illuminate a potential mechanism for sexual minorities' resilience and provide support for relational cultural theory. Understanding resilience factors among sexual minorities is critical for culturally sensitive and affirmative clinical practice and future research. PMID- 26380835 TI - Two case reports of bilateral adrenal myelolipomas. AB - Primary adrenal myelolipoma is a rare, non-functioning adrenal benign tumor that is composed of mature adipose tissue and a variable amount of haemopoietic elements. Clinically, it is difficult to get diagnosed with adrenal myelolipoma because the patient usually doesn't have obvious symptoms and signs in early stage. In the present study, two cases of primary bilateral adrenal myelolipomas are reported. Clinical presentation, imaging diagnostic features, histopathological changes and surgical treatments of the two patients are discussed. Preoperative diagnostic imaging examinations (B-mode ultrasonography, computed tomography and magnetic resonance imaging sans) assisted getting a prediction diagnosis of bilateral adrenal myelolipomas. A two-stage surgery was used to successfully excise bilateral adrenal myelolipomas in the two patients. Conventional open adrenalectomy was applied to remove the adrenal myelolipomas greater than 6 cm, and laparoscopic adrenalectomy was performed to excise the adrenal tumors smaller than 6 cm. Bilateral adrenal myelolipomas of the two patients were finally confirmed by postoperative histopathological examinations. Understanding clinical, imaging diagnostic and histopathological features of bilateral adrenal myelolipomas will facilitate timely diagnosis and treatment of this condition. Surgical removal of bilateral adrenal myelolipomas is safe, curative and beneficial. The two-stage surgery appears to be the best treatment option for the patients with bilateral adrenal myelolipomas because it achieves optimal treatment effectiveness with minimized sequelae. PMID- 26380837 TI - Data for comparative proteomics of ovaries from five non-model, crustacean amphipods. AB - Ovaries were taken from five sexually mature amphipods: Gammarus fossarum, Gammarus pulex, Gammarus roeseli, Hyallela azteca and Parhyale hawaiensis. The soluble proteome extracted from individual pair of ovaries from five biological replicates was trypsin digested and the resulting peptides were analyzed by high resolution tandem mass spectrometry. The spectra were assigned with four protein sequence databases with different specificities: a RNAseq-derived G. fossarum database; a RNAseq-derived P. hawaiensis database; both originating from ovaries transcriptome; the Daphnia pulex database derived from whole-genome sequencing and the NCBInr database. The best interpretation was obtained for most animals with the specific RNA-seq protein database previously established by means of RNAseq carried out on G. fossarum. Proteins identified in the five amphipod species allow defining the core-proteome of female reproductive tissues of the Senticaudata suborder. The data accompanying the manuscript describing the database searches and comparative analysis Trapp et al., 2015 [1] have been deposited to the ProteomeXchange with identifiers PXD002253 (G. fossarum), PXD002254 (G. pulex), PXD002255 (G. roeseli), PXD002256 (H. Azteca), and PXD002257 (P. hawaiensis). PMID- 26380838 TI - Infrared thermography videos of the elastocaloric effect for shape memory alloys NiTi and Ni2FeGa. AB - Infrared thermogrpahy was utilized to record the temperature change during tensile loading cycles of two shape memory alloy single crystals with pseudoelastic behavior. During unloading, a giant temperature drop was measured in the gage section due to the elastocaloric effect. This data article provides a video of a [001] oriented Ni2FeGa single crystal, including the corresponding stress-strain curve, shows the temperature drop over one cycle. The second video of a [148] oriented NiTi single crystal depicts the repeatability of the elastocaloric effect by showing two consecutive cycles. The videos are supplied in this paper. For further analysis and enhanced discussion of large temperature change in shape memory alloys, see Pataky et al. [1]. PMID- 26380839 TI - Survey of viral populations within Lake Michigan nearshore waters at four Chicago area beaches. AB - In comparison to the oceans, freshwater environments represent a more diverse community of microorganisms, exhibiting comparatively high levels of variability both temporally and spatially Maranger and Bird, Microb. Ecol. 31 (1996) 141-151. This level of variability is likely to extend to the world of viruses as well, in particular bacteria-infecting viruses (bacteriophages). Phages are known to influence bacterial diversity, and therefore key processes, in environmental niches across the globe Clokie et al., Bacteriophage 1 (2011) 31-45; Jacquet et al., Adv. Ocean Limn. 1 (2010) 97-141; Wilhelm and Suttle, Bioscience 49 (1999) 781-788; Bratback et al., Microb. Ecol. 28 (1994) 209-221. Despite their prevalence and likely critical role in freshwater environments, very few viral species have been characterized. Metagenomic approaches, however, have allowed for a glimpse into phage diversity. We collected surface water samples from four Chicago area beaches - Gillson Park, Montrose Beach, 57th Street Beach, and Calumet Beach - every two weeks from May 13 through August 5, 2014. Sampling was conducted with four biological replicates for each sampling date and location, resulting in 112 samples. DNA isolated from each of the individual samples for a given collection date/location was pooled together, with one exception - Calumet Beach on August 5, 2014 - in which each biological replicate was sequenced individually. Raw sequence data is available via NCBI's SRA database (part of BioProject PRJNA248239). PMID- 26380840 TI - Dataset for the validation and use of DiameterJ an open source nanofiber diameter measurement tool. AB - DiameterJ is an open source image analysis plugin for ImageJ. DiameterJ produces ten files for every image that it analyzes. These files include the images that were analyzed, the data to create histograms of fiber radius, pore size, fiber orientation, and summary statistics, as well as images to check the output of DiameterJ. DiameterJ was validated with 130 in silico-derived, digital, synthetic images and 24 scanning electron microscope (SEM) images of steel wire samples with a known diameter distribution. Once validated, DiameterJ was used to analyze SEM images of electrospun polymeric nanofibers, including a comparison of different segmentation algorithms. In this article, all digital synthetic images, SEM images, and their segmentations are included. Additionally, DiameterJ's raw output files, and processed data is included for the reader. The data provided herein was used to generate the figures in DiameterJ: A Validated Open Source Nanofiber Diameter Measurement Tool[1], where more discussion can be found. PMID- 26380841 TI - Data from a proteomic baseline study of Assemblage A in Giardia duodenalis. AB - Eight Assemblage A strains from the protozoan parasite Giardia duodenalis were analysed using label-free quantitative shotgun proteomics, to evaluate inter- and intra-assemblage variation and complement available genetic and transcriptomic data. Isolates were grown in biological triplicate in axenic culture, and protein extracts were subjected to in-solution digest and online fractionation using Gas Phase Fractionation (GPF). Recent reclassification of genome databases for subassemblages was evaluated for database-dependent loss of information, and proteome composition of different isolates was analysed for biologically relevant assemblage-independent variation. The data from this study are related to the research article "Quantitative proteomics analysis of Giardia duodenalis Assemblage A - a baseline for host, assemblage and isolate variation" published in Proteomics (Emery et al., 2015 [1]). PMID- 26380843 TI - Microscopic images dataset for automation of RBCs counting. AB - A method for Red Blood Corpuscles (RBCs) counting has been developed using RBCs light microscopic images and Matlab algorithm. The Dataset consists of Red Blood Corpuscles (RBCs) images and there RBCs segmented images. A detailed description using flow chart is given in order to show how to produce RBCs mask. The RBCs mask was used to count the number of RBCs in the blood smear image. PMID- 26380842 TI - Inhibition of DNA nanotube-conjugated mTOR siRNA on the growth of pulmonary arterial smooth muscle cells. AB - Here we provide raw and processed data and methods behind mTOR siRNA loaded DNA nanotubes (siRNA-DNA-NTs) in the growth of pulmonary arterial smooth muscle cells (PASMCs) under both normoxic and hypoxic condition, and also related to (You et al., Biomaterials, 2015, 67:137-150, [1]). The MTT analysis, Semi-quantitative RT PCR data presented here were used to probe cytotoxicity of mTOR siRNA-DNA-NT complex in its TAE-Mg(2+) buffer. siRNA-DNA-NTs have a lower cytotoxicity and higher transfection efficiency and can, based on inhibition of mTOR expression, decrease PASMCs growth both hypoxic and normal condition. PMID- 26380844 TI - Cognitive testing in older primary care patients: A cluster-randomized trial. AB - INTRODUCTION: This study investigated whether neuropsychological testing in primary care (PC) offices altered physician-initiated interventions related to cognitive impairment (CI) or slowed the rate of CI progression. METHODS: This 24 month, cluster-randomized study included 11 community-based PC practices randomized to either treatment as usual (5 practices) or cognitive report (CR; 6 practices) arms. From 2005 to 2008, 533 patients aged >=65 years and without a diagnosis of CI were recruited; 423 were retested 24 months after baseline. RESULTS: CR physicians were significantly more likely to order cognitive-related interventions (P = .02), document discussions about cognition (P = .003), and order blood tests to rule out reversible CI (P = .002). At follow-up, significantly more CR patients had a medication for cognition listed in their chart (P = .02). There was no difference in the rate of cognitive decline between the groups. DISCUSSION: Providing cognitive information to physicians resulted in higher rates of physician-initiated interventions for patients with CI. PMID- 26380845 TI - Robotics in Colonoscopy. AB - Colorectal cancer is the second leading cause of mortality in men and women in the United States. While there is a definite advantage regarding the use of colonoscopies in screening, there is still a lack of widespread acceptance of colonoscopy use in the general public. This is evident by the fact that up to 75% of patients diagnosed with colorectal cancer present with locally advanced disease. In order to make colonoscopy and in turn colorectal cancer screening a patient friendly and a comfortable test some changes in tool are necessary. The conventional colonoscope has not changed much since its development. There are several new advances in colorectal screening practices. One of the most promising new advances is the advent of robotic endoscopic techniques. PMID- 26380847 TI - Posttranslational Modifications and Secretion of the Hedgehog (Hh) Proteins. Preface. PMID- 26380846 TI - Response to Comments on "Magnetic Resonance Spectroscopy Identifies Neural Progenitor Cells in the Live Human Brain". AB - We reported on a neural progenitor cell biomarker, a lipid-based metabolite enriched in these cells, which we detected using spectroscopy both in vitro and in vivo, and singular value decomposition-based signal processing. The study provided an outline of our computational methodology. Herein, we report more extensively on the method of spectrum analysis used, demonstrating the specificity of our findings. PMID- 26380848 TI - Preface. PMID- 26380849 TI - Developing the evidentiary basis for family medicine in the global context: The Besrour Papers: a series on the state of family medicine in the world. AB - OBJECTIVE: To provide an overview of the main methodologic challenges to finding definitive evidence of the positive effects of family medicine and family medicine training on a global scale. COMPOSITION OF THE COMMITTEE: In 2012, 2013, and 2014, the College of Family Physicians of Canada hosted the Besrour Conferences to reflect on its role in advancing the discipline of family medicine globally. The Besrour Papers Working Group, which was struck at the 2013 conference, was tasked with developing a series of papers to highlight the key issues, lessons learned, and outcomes emerging from the various activities of the Besrour collaboration. The working group comprised members of various academic departments of family medicine in Canada and abroad who attended the conferences. METHODS: We performed a scoping review to determine the methodologic obstacles to understanding the positive effects of family medicine globally. REPORT: The main obstacle to evaluating family medicine globally is that one of its core dimensions and assets is its local adaptability. Family medicine takes on very different roles in different health systems, making aggregation of data difficult. In many countries family medicine competes with other disciplines rather than performing a gatekeeping role. Further, most research that has been conducted thus far comes from industrialized contexts, and patient continuity and its benefits might not be achievable in the short term in developing countries when clinical demands are great. We must find frameworks to permit strengthening the evidentiary basis of the discipline across different contexts without sacrificing its beneficial adaptability. CONCLUSION: We believe that developing family medicine and its attributes is one of the keys to achieving global health. These attributes-including its comprehensiveness, adaptability, and attention to both local and patient needs-are key to advancing global health priorities, but make common evaluative frameworks for the discipline a challenge. The spread of family medicine over the past decades is indirect evidence of its utility, but we need to generate more evidence. We present some of the initial challenges to a broader and more rigorous evaluative framework. PMID- 26380850 TI - Models of primary care for frail patients. AB - OBJECTIVE: To discuss models of care for frail seniors provided in primary care settings and those developed by Canadian FPs. SOURCES OF INFORMATION: Ovid MEDLINE and the Cochrane database were searched from 2010 to January 2014 using the terms models of care, family medicine, elderly, and geriatrics. MAIN MESSAGE: New models of funding for primary care have opened opportunities for ways of caring for complex frail older patients. Severity of frailty is an important factor, and more severe frailty should prompt consideration of using an alternate model of care for a senior. In Canada, models in use include integrated care systems, shared care models, home-based care models, and family medicine specialty clinics. No one model should take precedence but FPs should be involved in developing and implementing strategies that meet the needs of individual patients and communities. Organizational and remunerative supports will need to be put in place to achieve widespread uptake of such models. CONCLUSION: Given the increased numbers of frail seniors and the decrease in access to hospital beds, prioritized care models should include ones focused on optimizing health, decreasing frailty, and helping to avoid hospitalization of frail and well seniors alike. The Health Care of the Elderly Program Committee at the College of Family Physicians of Canada is hosting a repository for models of care used by FPs and is asking physicians to submit their ideas for how to best care for frail seniors. PMID- 26380851 TI - Retraction notice to "A randomised prospective study of two different combined internal and external fixation techniques for distal tibia shaft fractures" [Injury 45 (2014) 1990 - 1995]. PMID- 26380853 TI - Foreword. PMID- 26380852 TI - Dietary exclusion for childhood atopic dermatitis. AB - QUESTION: Atopic dermatitis (AD) (eczema) is very common in childhood. Parents are often concerned that food allergy plays a role in their child's eczema presentation and practise elimination diets for symptom control. Should I recommend that children with AD eliminate cow's milk or eggs from their diets? ANSWER: There is insufficient evidence about the benefit of eliminating cow's milk in unselected patients with AD. Some evidence suggests that egg elimination might benefit those children with AD who are suspected of being allergic to eggs and who are sensitized to eggs; however, more research is needed in this population to guide the use of food elimination. Prolonged elimination diets that are not physician guided also put patients at risk of nutritional deficiencies and failure to thrive, and might actually contribute to the development of clinical food allergy. PMID- 26380854 TI - Global Health in Family Medicine Summer Primer: Course for residents and faculty. AB - PROBLEM ADDRESSED: Despite the rapid emergence of global health training across North American universities, there remains a gap in educational programs focusing on the unique role of family medicine and primary care in global health. OBJECTIVE OF PROGRAM: The objective of the Global Health in Family Medicine Summer Primer, developed in 2013 by the Department of Family and Community Medicine at the University of Toronto in Ontario, is to strengthen global health competencies among family medicine residents and faculty. PROGRAM DESCRIPTION: The course covers the meaning of global health; global health ethics; the place of family medicine, primary care, and primary health care in the global health context; epidemiology; infectious diseases; the social determinants of health; and care of vulnerable populations locally and globally. The course is delivered in an intensive 5-day format with didactic lectures, group discussions, interactive workshops, and lived-experience panels. CONCLUSION: The Global Health in Family Medicine Summer Primer has proven to be a successful educational initiative and provides valuable lessons learned for other academic science centres in developing global health training programs for family medicine residents and faculty. PMID- 26380855 TI - Care of adults with developmental disabilities: Effects of a continuing education course for primary care providers. AB - OBJECTIVE: To evaluate the effects of an interdisciplinary, guideline-based continuing education course on measures related to the care of adults with developmental disabilities (DD). DESIGN: Before-and-after study with a control group. SETTING: Ontario. PARTICIPANTS: Forty-seven primary care providers (physicians, registered nurses, and nurse practitioners). INTERVENTION: Participants either only received reference material about primary care of people with DD (control group) or participated in a continuing education course on primary care of people with DD in addition to receiving the reference material (intervention group). MAIN OUTCOME MEASURES: Participants reported on 5 key measures related to care of adults with DD: frequency of using guidelines, frequency of performing periodic health examinations, frequency of assessing patients who present with behaviour changes, level of comfort while caring for adults with DD, and knowledge of primary care related to adults with DD. RESULTS: Over time, the intervention group showed significant increases in 4 of the 5 key measures of care compared with the control group: the frequency of guideline use (P < .001), frequency of assessment of patients' behaviour change (P = .03), comfort level in caring for people with DD (P = .01), and knowledge of primary care related to adults with DD (P = .01). CONCLUSION: A continuing education course on primary care of adults with DD is a useful interdisciplinary model to train health professionals who provide primary care services to these patients. PMID- 26380856 TI - Rural family medicine training site: Proposed framework. AB - OBJECTIVE: To develop a framework for a successful rural family medicine training program and to assess the potential for a rural family medicine residency training program using the Weyburn and Estevan areas of Saskatchewan as test sites. DESIGN: A mixed-method design was used; however, the focus of this article was on the qualitative data collected. Questions formulated for the semistructured interviews evolved from the literature. SETTING: Rural Saskatchewan. PARTICIPANTS: Community physicians and representatives from the Sun Country Regional Health Authority, the Saskatchewan Ministry of Health, and the University of Saskatchewan. METHODS: The data were documented during the interviews using a laptop computer, and the responses were reviewed with participants at the end of their interviews to ensure accuracy. The qualitative data collected were analyzed using inductive thematic analysis. MAIN FINDINGS: Through the analysis of the data several themes emerged related to implementing a rural family medicine residency training program. Key predictors of success were physical resources, physician champions, physician teachers, educational support, administrative support, and other specialist support. Barriers to the development of a rural family medicine training site were differing priorities, lack of human resources, and lack of physical resources. CONCLUSION: A project of this magnitude requires many people at different levels collaborating to be successful. PMID- 26380857 TI - Author reply: To PMID 25209356. PMID- 26380858 TI - Preface. PMID- 26380859 TI - Cooking Oils. PMID- 26380860 TI - Assessment of Polarity in GaN Self-Assembled Nanowires by Electrical Force Microscopy. AB - In this work, we demonstrate the capabilities of atomic force microscopies (AFMs) for the nondestructive determination of the polarity of GaN nanowires (NWs). Three complementary AFMs are analyzed here: Kelvin probe force microscopy (KPFM), light-assisted KPFM, and piezo-force microscopy (PFM). These techniques allow us to assess the polarity of individual NWs over an area of tens of MUm(2) and provide statistics on the polarity of the ensemble with an accuracy hardly reachable by other methods. The precise quantitative analysis of the tip-sample interaction by multidimensional spectroscopic measurements, combined with advanced data analysis, has allowed the separate characterization of electrostatic and van der Waals forces as a function of tip-sample distance. Besides their polarity, the net surface charge density of individual NWs was estimated. PMID- 26380861 TI - Asthma and asthma medication use among 4-year-old offspring of subfertile couples -association with IVF? AB - This study evaluated the prevalence of asthma and asthma medication use in 213 4 year-old singletons followed from birth onwards, including three groups of children born following: (i) controlled ovarian hyperstimulation IVF/intracytoplasmic sperm injection (ICSI); (ii) modified natural cycle IVF/ICSI; and (iii) natural conception in subfertile couples. The rate of asthma medication was higher in the ovarian hyperstimulation-IVF/ICSI than in the subfertile group (adjusted odds ratios [aOR]: 1.96 [1.00-3.84]). Time to pregnancy, a proxy for the severity of subfertility, was not associated with asthma and asthma medication. In conclusion, controlled ovarian hyperstimulation IVF/ICSI is associated with the use of asthma medication in 4-year-old offspring of subfertile couples. PMID- 26380862 TI - Cryopreservation and transplantation of ovarian tissue exclusively to postpone menopause: technically possible but endocrinologically doubtful. AB - Transplantation of cryopreserved ovarian tissue has been shown to induce pregnancies and puberty successfully. Therefore, using cryopreserved ovarian tissue to postpone menopause (tissue hormone therapy [THT]) seems to be an interesting option to avoid conventional menopause hormone therapy (MHT). Pregnancy induction and replacing MHT by THT, however, are completely different topics as different requirements need to be met. First, MHT requires long-lasting and continuous hormone production. It still needs to be proven if the transplanted tissue is active for at least 5 years with a continuous follicle growth to avoid phases with low oestrogen production, which would otherwise cause menopausal symptoms and could reduce the postulated benefit for women's health. Second, the advantage of a physiological hormone production over a non physiological MHT is still hypothetical. Third, women who have undergone hysterectomies who do not need progesterone for endometrial protection would only require oestrogens, imposing more health benefits (cardiovascular system, mammary gland) than oestrogen and progesterone production or replacement. Therefore, transplanting ovarian tissue exclusively to postpone menopause is endocrinologically doubtful and should only be carried out within clinical trials. PMID- 26380863 TI - Paternal obesity negatively affects male fertility and assisted reproduction outcomes: a systematic review and meta-analysis. AB - This systematic review investigated the effect of paternal obesity on reproductive potential. Databases searched were Pubmed, Ovid, Web of Science, Scopus, Cinahl and Embase. Papers were critically appraised by two reviewers, and data were extracted using a standardized tool. Outcomes were: likelihood of infertility, embryo development, clinical pregnancy, live birth, pregnancy viability, infant development, sperm; concentration, morphology, motility, volume, DNA fragmentation, chromatin condensation, mitochondrial membrane potential (MMP), and seminal plasma factors. Thirty papers were included, with a total participant number of 115,158. Obese men were more likely to experience infertility (OR = 1.66, 95% CI 1.53-1.79), their rate of live birth per cycle of assisted reproduction technology (ART) was reduced (OR = 0.65, 95% CI 0.44-0.97) and they had a 10% absolute risk increase of pregnancy non-viability. Additionally, obese men had an increased percentage of sperm with low MMP, DNA fragmentation, and abnormal morphology. Clinically significant differences were not found for conventional semen parameters. From these findings it can be concluded that male obesity is associated with reduced reproductive potential. Furthermore, it may be informative to incorporate DNA fragmentation analysis and MMP assessment into semen testing, especially for obese men whose results suggest they should have normal fertility. PMID- 26380864 TI - Non-invasive assessment of in-vitro embryo quality to improve transfer success. AB - Although IVF has been performed routinely for many years to help couples with fertility problems and in relation to modern breeding of farm animals, pregnancy rates after transfer to a recipient have not improved during the last decade. Early prediction of the viability of in-vitro developed embryos before the transfer to a recipient still remains challenging. Presently, the predominant non invasive technique for selecting viable embryos is based on morphology, where parameters such as rates of cleavage and blastocyst formation as well as developmental kinetics are evaluated mostly subjectively. The simple morphological approach is, however, inadequate for the prediction of embryo quality, and several studies have focused on developing new non-invasive methods using molecular approaches based particularly on proteomics, metabolomics and most recently small non-coding RNA, including microRNA. This review outlines the potential of several non-invasive in-vitro methods based on analysis of spent embryo culture medium. PMID- 26380865 TI - Karyomapping identifies second polar body DNA persisting to the blastocyst stage: implications for embryo biopsy. AB - Blastocyst biopsy is now widely used for both preimplantation genetic screening (PGS) and preimplantation genetic diagnosis (PGD). Although this approach yields good results, variable embryo quality and rates of development remain a challenge. Here, a case is reported in which a blastocyst was biopsied for PGS by array comparative genomic hybridization on day 6 after insemination, having hatched completely. In addition to a small trophectoderm sample, excluded cell fragments from the subzonal space from this embryo were also sampled. Unexpectedly, the array comparative genomic hybridization results from the fragments and trophectoderm sample were non-concordant: 47,XX,+19 and 46,XY, respectively. DNA fingerprinting by short tandem repeat and amelogenin analysis confirmed the sex chromosome difference but seemed to show that the two samples were related but non-identical. Genome-wide single nucleotide polymorphism genotyping and karyomapping identified that the origin of the DNA amplified from the fragments was that of the second polar body corresponding to the oocyte from which the biopsied embryo developed. The fact that polar body DNA can persist to the blastocyst stage provides evidence that excluded cell fragments should not be used for diagnostic purposes and should be avoided when performing embryo biopsies as there is a risk of diagnostic errors. PMID- 26380866 TI - Role of PAFAH1B1 in human spermatogenesis, fertilization and early embryonic development. AB - Spermatogenesis, fertilization and subsequent embryonic development are complex processes that require tight regulation. The PAFAH1B1 gene plays important roles in these reproductive events in mice, but its expression and roles in human reproduction have not been investigated. Expression analysis of testicular tissue by reverse transcription quantitative PCR and immunohistochemistry revealed varied expression levels among samples of different spermatogenic abilities (as assessed by the Johnsen score), with protein expression restricted to spermatogonia, spermatocytes and spermatids. Immunofluorescence on spermatozoa showed expression over the acrosome and midpiece regions of ejaculated samples, whereas a high proportion of percutaneous epididymal sperm aspiration-derived spermatozoa showed expression restricted to the midpiece. Analysis for PAFAH1B1 mRNA also revealed different expression levels among unfertilized oocytes, zygotes, cleavage stage embryos and blastocysts, with protein localized at the membrane level in oocytes and zygotes, and gradually distributing within the cytoplasm of cleavage stage embryos and blastocysts. Interestingly, microinjection of PAFAH1B1 siRNA into zygotes significantly (P = 0.024) increased fragmentation formation rates in subsequent embryonic development stages. Altogether, these are the first results to support a role for PAFAH1B1 in human spermatogenesis and early embryonic development. PMID- 26380867 TI - Preimplantation genetic risk reduction: a new dilemma in the era of chromosomal microarrays and exome sequencing. AB - New technologies are revealing genetic variants of unknown significance (VUS), raising questions about the indications that call for preimplanation genetic diagnosis (PGD). Two couples requesting PGD for VUS are presented. The first couple requested PGD for Lynch syndrome. Whole exome sequencing identified in a healthy male with a family history of Lynch-associated tumours, a MLH1 missense variant. The variant had not been reported as pathogenic, but was predicted as damaging by algorithms. The second couple had a child diagnosed with pervasive developmental disorder and intellectual disability, carrying a microduplication on chr:Xp.22.3, and a microdeletion on chr:17q21.31. The maternally inherited X linked microduplication was also present in the mother's healthy brother and daughter, whereas the chr17 microdeletion was a de-novo event. As chromosomal microarrays and whole-exome sequencing are becoming standard tests, couples are requesting PGD for these VUS. The risk of possible genetic diseases can be reduced by carrying out PGD for uncertain findings, yet will inevitably lead to the birth of affected children despite the transfer of embryos that are not carriers of the familial variants. Findings of unknown significance demand urgent discussion and guidelines for their use as a risk-reduction measure in the preimplantation setting. PMID- 26380868 TI - Obesity induced by cafeteria diet disrupts fertility in the rat by affecting multiple ovarian targets. AB - Obesity constitutes a health problem of increasing worldwide prevalence. Among the health detriments caused by obesity, reproduction is disrupted. However, the mechanisms involved in this disruption are not fully understood. Animals fed a cafeteria diet constitute the model for the study of obesity that most closely reflects Western diet habits. The aims of this study were to evaluate whether a cafeteria diet affects ovarian function and to contribute to the understanding of the mechanisms involved. For that purpose, 22-day-old female Wistar rats were fed ad libitum with a standard diet (control group; n = 20) or cafeteria diet (CAF group; n = 20). The cafeteria diet induced obesity and hyperglycaemia, without altering serum triglycerides, cholesterol or C-reactive protein concentrations. This diet also altered ovarian function: the rats showed prolonged dioestrous phases, decreased serum oestradiol concentrations and increased number of antral atretic follicles. Moreover, follicular cysts were detected in the CAF group, concomitantly with a decrease in the number of anti-Mullerian hormone immunoreactive pre-antral follicles and COX-2-positive antral and pre-ovulatory follicles. The authors conclude that a cafeteria diet reduces ovarian reserve, induces the presence of follicular cysts and disturbs the ovulatory process, leading to the delayed pregnancy observed in these animals. PMID- 26380869 TI - MTHFR-Ala222Val and male infertility: a study in Iranian men, an updated meta analysis and an in silico-analysis. AB - Methylenetetrahydrofolate reductase (MTHFR) functions as a main regulatory enzyme in folate metabolism. The association of MTHFR gene Ala222Val polymorphism with male infertility in an Iranian population was investigated by undertaking a meta analysis and in-silico approach. A genetic association study included 497 men; 242 had unexplained infertility and 255 were healthy controls. Polymerase chain reaction restriction fragment length polymorphism was used for genotyping MTHFR Ala222Val. OpenMeta[Analyst] software was used to conduct the analysis; 22 studies were identified by searching PubMed and the currently reported genetic association study. A novel in-silico approach was used to analyse the effects of Ala222Val substitution on the structure of mRNA and protein. Genetic association study revealed a significant association of MTHFR-222Val/Val genotype with oligozoospermia (OR 2.32; 95% CI, 1.12 to 4.78; P = 0.0451) and azoospermia (OR 2.59; 95% CI 1.09 to 6.17; P = 0.0314). Meta-analysis for allelic, dominant and codominant models showed a significant association between Ala222Val polymorphism and the risk of male infertility (P < 0.001). In silico-analysis showed MTHFR Ala222Val affects enzyme structure and could also change the mRNA properties (P = 0.1641; P < 0.2 is significant). The meta-analysis suggested significant association of MTHFR-Ala222Val with risk of male infertility, especially in Asian populations. PMID- 26380870 TI - Fertility-preservation counselling and treatment for medical reasons: data from a multinational network of over 5000 women. AB - Fertility-preservation techniques for medical reasons are increasingly offered in national networks. Knowledge of the characteristics of counselled patients and techniques used are essential. The FertiPROTEKT network registry was analysed between 2007 and 2013, and included up to 85 university and non-university centres in Germany, Austria and Switzerland; 5159 women were counselled and 4060 women underwent fertility preservation. In 2013, fertility-preservation counselling for medical reasons increased significantly among nullipara and women aged between 21 and 35 years (n = 1043; P < 0.001). Frequency of GnRH applications slowly decreased, whereas tissue, oocytes and zygote cryopreservation increased. In 2013, women with breast cancer mainly opted for tissue freezing, whereas women with lymphoma opted for GnRH agonist. Women younger than 20 years predominantly opted for GnRH agonists and ovarian tissue cryopreservation; women aged between 20 and 40 years underwent a variety of techniques; and women over 40 years opted for GnRH agonists. The average number of aspirated oocytes per stimulation cycle decreased as age increased (< 30 years: 12.9; 31-35 years: 12.3; 36-46: 9.0; > 41 years: 5.7). For ovarian tissue cryopreservation, removal and cryopreservation of fewer than one ovary was preferred and carried out in 97% of cases in 2013. PMID- 26380871 TI - Prognostic Biomarkers for Hodgkin Lymphoma. AB - The prognosis of patients with classical Hodgkin lymphoma following chemo- and radiotherapy has been excellent during the last 4 decades. However, the development of secondary malignancies is of major concern. Therefore, the reduction of radiotherapy application is a major objective of ongoing clinical trials. De-escalation of treatment may increase the risk of relapses and thus may lead to reappearance of prognostic factors. Prognostic biomarkers might help to identify patients who are at increased risk of relapse. This review summarizes the current knowledge about potential prognostic biomarkers for patients with classical Hodgkin lymphoma. PMID- 26380872 TI - Homochiral [2]Catenane and Bis[2]catenane from Alleno-Acetylenic Helicates - A Highly Selective Narcissistic Self-Sorting Process. AB - Homochiral strands of alternating alleno-acetylenes and phenanthroline ligands (P)-1 and (P2)-2, as well as their corresponding enantiomers, selectively assemble with the addition of silver(I) salt to yield dinuclear and trinuclear double helicates, respectively. Upon increasing the solvent polarity, the dinuclear and trinuclear helicates interlock to form a [2]catenane and bis[2]catenane, bearing 14 chirality elements, respectively. The solid-state structure of the [2]catenane reveals a nearly perfect fit of the interlocked strands, and the ECD spectra show a significant amplification of the chiroptical properties upon catenation, indicating stabilization of the helical secondary structure. Highly selective narcissistic self-sorting was demonstrated for a racemic mixture consisting of both short and long alleno-acetylenic strands, highlighting their potential for the preparation of linear catenanes of higher order. PMID- 26380873 TI - National trends in hospital-treated self-harm events among middle-aged adults. AB - OBJECTIVE: To assess national trends in hospital-treated self-harm events focusing on adults aged 45-64years. METHOD: Healthcare Cost and Utilization Project data from 2001 (N=7,452,727) to 2011 (N=7,893,587) were used to assess national trends in hospital stays for suicide and self-inflicted injury among youth (0-24years), young adults (35-44years), middle-aged adults (45-64years) and older adults (>=65years). RESULTS: Among middle-aged adults, hospital-treated self-harm events increased from 5.1 (2001) to 7.1 (2011) per 10,000 population (OR=1.4, 95% CI=1.2, 1.6). This increase was larger than corresponding changes among youth (5.2-4.9) (interaction P=.0003), young adults (10.0-10.6) (interaction P=.006) or older adults (2.2-2.4) (interaction P=.07). Among middle aged adults, hospital-treated self-harm events per 100 hospital discharges significantly increased (OR=1.4, 95% CI=1.3, 1.6), but there was not a significant increase in self-harm discharges per 100 mental disorder discharges (OR=1.2, 95% CI=1.0, 1.4). CONCLUSIONS: Between 2001 and 2011, there was a disproportionate national increase in hospital-treated self-harm events among middle-aged adults that mirrored national trends in suicide. Because the increase was largely accounted for by an overall increase in mental health hospitalizations of middle-aged adults, the rising rate of hospital-treated self harm events may reflect broader population-based mental health challenges facing US middle-aged adults. PMID- 26380874 TI - Predictors of inpatient psychiatric admission in patients presenting to the emergency department: the role of dimensional assessment. AB - OBJECTIVE: To identify which patient factors predict psychiatric hospitalization in patients presenting to the emergency department and to examine the role of the dimensional approach to psychopathology in predicting hospitalization. METHODS: We consecutively recruited 312 patients undergoing psychiatric evaluation in the emergency room of a hospital in Rome over a 6-month period. Patients were rated on the SVARAD (Scala per la Valutazione Rapida Dimensionale), a scale designed for the rapid assessment of the main psychopathological dimensions. Information about patient history, as well as sociodemographic and clinical variables, was also collected. Univariate analysis was performed to detect the variables associated with recommendation of psychiatric hospitalization. Multiple logistic regression analysis was used to identify independent predictors of hospitalization and compare their strength. A replication study was performed in another hospital on a random sample of 118 patients. RESULTS: In both studies, patients who were recommended for psychiatric hospitalization showed significantly higher levels of anger/aggressiveness, apathy, impulsivity, reality distortion, thought disorganization and activation. Multivariate analysis identified psychopathological dimensions (reality distortion, impulsivity, apathy), diagnosis of psychotic or mood disorders and proposal for compulsory admission as independent predictors of psychiatric hospitalization. Hierarchical regression analysis revealed that the dimensional evaluation was the strongest predictor. CONCLUSIONS: Our findings suggest that, in emergency setting, a systematic dimensional assessment may usefully complement the categorical assessment. Future research should aim at developing an operational assessment model, including both categorical and dimensional approaches to psychopathology. PMID- 26380875 TI - Differences in clinical and psychiatric outcomes between prevalent HIV-1 molecular subtypes in a multiethnic Southeast Asian sample. AB - OBJECTIVE: In Southeast Asia, subtypes B and CRF01_AE are the prevalent human immunodeficiency virus-1 (HIV-1) subtypes. This study examines the intersubtype differences in clinical indicators and psychiatric symptoms in a multiethnic sample. METHODS: The study site was a national HIV treatment center. Data were extracted from the Molecular Epidemiology Research study and the HIV-Psychiatry Integrated Mental Health Project, and analyzed according to groups defined by viral subtype. RESULTS: Of 177 subjects, 54.8% were infected with subtype CRF01_AE; 42.9% screened positive on the Hospital Anxiety and Depression Scale (HADS). The CRF01_AE group was significantly older (mean 38.29 years vs. 34.62 years, P=.031) and had advanced immunosuppression (CD4 <200) just prior to HADS screening (33.0% vs. 13.5%, P=.003). By multivariate logistic regression, homosexual transmission [odds ratio (OR) 0.388, 95% confidence interval (CI) 0.158-0.951, P=.038], subtype CRF01_AE (OR 2.898, 95% CI 1.199-7.001, P=.018) and positive HADS screening (OR 2.859, 95% CI 1.261-8.484, P=.012) were associated with advanced immunosuppression; and only advanced immunosuppression was associated with screening positive on the HADS (OR 3.270, 95% CI 1.299-8.227, P=.012). CONCLUSION: Subtype CRF01_AE is associated with advanced immunosuppression but not with symptoms of anxiety and depression. The results suggest that psychiatric symptoms are associated with advanced HIV disease regardless of subtype. PMID- 26380876 TI - VA mental health clinician experiences and attitudes toward OpenNotes. AB - OBJECTIVE: To describe Department of Veterans Affairs (VA) mental health clinician attitudes toward and experiences with OpenNotes (also known as Blue Button), which provides patients direct access to clinical notes online. METHOD: A 35-item online survey was administered to 263 mental health clinicians and nurses from one VA Medical Center. RESULTS: Seventy-nine percent of eligible subjects participated. Most respondents agreed or somewhat agreed that OpenNotes is a good idea in general, but only half agreed that making mental health notes available online is a good idea. Most believed that patients will better remember plans of care and be better prepared for visits. Most also felt that patients will worry more and request changes in notes. Many clinicians reported being less detailed and changing the tone of their notes. CONCLUSION: As a group, mental health clinicians are positive about OpenNotes in general but ambivalent about the use of OpenNotes in mental health care. The results call for research on outcomes of OpenNotes use in mental health and to develop education and support to help clinicians adapt to OpenNotes. PMID- 26380877 TI - Impact of a change in protected environment on the occurrence of severe bacterial and fungal infections in children undergoing hematopoietic stem cell transplantation. AB - BACKGROUND: Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a procedure with a high infection risk. Strict isolation of patients is the rule to prevent such condition. OBJECTIVE: We compared the occurrence of severe infections (bacteremia and invasive fungal infection, IFI) in children undergoing alloHSCT before and after the move to a new protected unit with decreases in isolation methods. METHODS: The study was conducted over a 10-year period. Unit 1 (2002-2007) consisted of laminar airflow rooms where caregivers were required to wear a sterile outfit (gown, gloves, hat, and mask). Unit 2 (2008-2012) included spacious positive air pressure rooms with HEPA filters where only a clean gown and mask were required to be worn. RESULTS: Two hundred eighty-six alloHSCTs were performed (144 in Unit 1 and 142 in Unit 2). We reported a total incidence of 4.78 infections/1000 hospital-days including 4.4 episodes of bacteremia and 0.38 episodes of IFI. There was no statistical difference in the incidence of infections: n = 4.98/1000 hospital-days in Unit 1 vs. n = 4.6/1000 in Unit 2 (P = 0.63). CONCLUSION: The lack of difference in the occurrence of severe infection supports our decision to decrease unnecessary high protection in alloHSCT units to improve children's daily life. PMID- 26380878 TI - Large-scale multi-site OSCEs for national competency examination of medical doctors in Indonesia. AB - BACKGROUND: Implementing large-scale multi-site objective structured clinical examination (OSCEs) for national competency examination in a low resource country is challenging. AIMS: To describe the first national OSCE for national competency examination of medical doctors in Indonesia and evaluate the reliability, validity, feasibility, acceptability, and educational impact. METHODS: We collected electronically the OSCE scores from 49 out of 73 medical schools that participated to assess reliability and validity. We conducted electronic survey to examiners, examinees, SP trainers, and OSCE coordinators to assess feasibility, acceptability, and educational impact. RESULTS: The Cronbach's alpha coefficient across station was 0.79. There was strong correlation between rubric and global rating scores in each station (coefficient correlation ranges from 0.705 to 0.82). The content validity ratio was 0.97. The coefficient correlation between OSCE and MCQ was 0.335 (p = 0.00). All 49 medical schools were able to conduct OSCE simultaneously. Examiners, examinees, SP trainers, and OSCE coordinators had good perception regarding feasibility and acceptability of OSCE. Both examiners and examinees indicated good educational impact of OSCE application. The cutting score based on the borderline regression method was 61.96%. There were 67.39% of the examinees achieved similar or above the cutting score. CONCLUSION: With 12 stations 15 min each, the reliability coefficient across station is intermediate. Content validity is good. It is feasible and acceptable to implement large-scale multi-site OSCEs in Indonesia. Examiners and examinees perceive good educational impact on OSCE implementation. PMID- 26380879 TI - Immunomodulatory Potency of Microcystin, an Important Water-Polluting Cyanobacterial Toxin. AB - Microcystins (MCs) are primarily hepatotoxins produced by cyanobacteria and are responsible for intoxication in humans and animals. There are many incidents of chronic exposure to MCs, which have been attributed to the inappropriate treatment of water supplies or contaminated food. Using RAW 264.7 macrophages, we showed the potency of microcystin-LR (MC-LR) to stimulate production of pro inflammatory cytokines (tumor necrosis factor alpha and interleukin-6) as a consequence of fast nuclear factor kappaB and nitrogen-activated protein kinase activation. In contrast to other studies, the observed effects were not attributed to the intracellular inhibition of protein phosphatases 1/2A due to lack of specific transmembrane transporters for MCs. However, the MC-LR-induced activation of macrophages was effectively inhibited by a specific peptide that blocks signaling of receptors, which play a pivotal role in the innate immune responses. Taken together, we showed for the first time that MC-LR could interfere with macrophage receptors that are responsible for triggering the above mentioned signaling pathways. These findings provide an interesting mechanistic explanation of some adverse health outcomes associated with toxic cyanobacteria and MCs. PMID- 26380880 TI - Crystal structure and tartrate inhibition of Legionella pneumophila histidine acid phosphatase. AB - Histidine acid phosphatases (HAPs) utilize a nucleophilic histidine residue to catalyze the transfer of a phosphoryl group from phosphomonoesters to water. HAPs function as protein phosphatases and pain suppressors in mammals, are essential for Giardia lamblia excystation, and contribute to virulence of the category A pathogen Francisella tularensis. Herein we report the first crystal structure and steady-state kinetics measurements of the HAP from Legionella pneumophila (LpHAP), also known as Legionella major acid phosphatase. The structure of LpHAP complexed with the inhibitor l(+)-tartrate was determined at 2.0 A resolution. Kinetics assays show that l(+)-tartrate is a 50-fold more potent inhibitor of LpHAP than of other HAPs. Electrostatic potential calculations provide insight into the basis for the enhanced tartrate potency: the tartrate pocket of LpHAP is more positive than other HAPs because of the absence of an ion pair partner for the second Arg of the conserved RHGXRXP HAP signature sequence. The structure also reveals that LpHAP has an atypically expansive active site entrance and lacks the nucleotide substrate base clamp found in other HAPs. These features imply that nucleoside monophosphates may not be preferred substrates. Kinetics measurements confirm that AMP is a relatively inefficient in vitro substrate of LpHAP. PMID- 26380881 TI - The persistence of pertussis and developments in vaccination strategies. PMID- 26380882 TI - Pakistan Government faces legal challenge over images on tobacco packaging. PMID- 26380883 TI - Thomas "Tommy" Francis Jr. PMID- 26380885 TI - The real challenge is to make e-cigarettes accessible for poor smokers--Author's reply. PMID- 26380886 TI - The real challenge is to make e-cigarettes accessible for poor smokers. PMID- 26380887 TI - New guideline on treatment of idiopathic pulmonary fibrosis. PMID- 26380889 TI - Corrections. PMID- 26380888 TI - Invasive mediastinal staging is irrelevant for PET/CT positive N2 lung cancer if the primary tumour and ipsilateral lymph nodes are resectable. PMID- 26380890 TI - Corrections. PMID- 26380891 TI - Design Principles for Nanoparticles Enveloped by a Polymer-Tethered Lipid Membrane. AB - We propose the design for a nanoparticle carrier that combines three existing motifs into a single construct: a liposome is stabilized by anchoring it to an enclosed solid core via extended polymeric tethers that are chemically grafted to the core and physisorb into the surrounding lipid membrane. Such a design would exhibit several enticing properties, among them: (i) the anchoring stabilizes the liposome against a variety of external stresses, while preserving an aqueous compartment between core and membrane; (ii) the interplay of design parameters such as polymer length or grafting density enforces strong constraints on nanoparticle size and hence ensures a high degree of uniformity; and (iii) the physical and chemical characteristics of the individual constituents equip the construct with numerous functionalities that can be exploited in many ways. However, navigating the large parameter space requires a sound prior understanding for how various design features work together, and how this impacts potential pathways for synthesizing and assembling these nanoparticles. In this paper, we examine these connections in detail, using both soft matter theory and computer simulations at all levels of resolution. We thereby derive strong constraints on the experimentally relevant parameter space, and also propose potential equilibrium and nonequilibrium pathways for nanoparticle assembly. PMID- 26380892 TI - Fish Oil Supplementation and Quality of Life in Stage II Colorectal Cancer Patients: A 24-Month Follow-Up Study. AB - Research suggests that cancer survivors have an interest in lifestyle changes following a diagnosis. However, few studies have prospectively investigated whether these changes result in positive outcomes. The objective of this study was to examine the associations between fish oil supplementation and quality of life (QoL), cancer recurrence, and all-cause mortality in Stage 2 colorectal cancer (CRC) patients following diagnosis. Four hundred fifty-three patients were enrolled from the North Carolina Cancer Registry from 2009 to 2011. Data on demography, treatment, and health behaviors were collected at diagnosis, 12-, and 24 mo postdiagnosis. Generalized estimating equations were performed to examine fish oil supplementation in relation to QoL, recurrence, and all-cause mortality. An increase in fish oil supplementation over 24 mo postdiagnosis was associated with an increase in the physical component score of the 12-item Medical Outcomes Short Form (beta = 2.43, 95% CI: 0.10-4.76). Supplementation showed no association with the Functional Assessment of Cancer-Colorectal, cancer recurrence or mortality across the 24-mo follow-up. This study suggests that fish oil supplementation may improve symptom-related QoL (i.e., physical functioning) in Stage 2 CRC patients following diagnosis. Future research should address the dose-dependent effects of this relationship. PMID- 26380893 TI - Wire-in-Tube IrOx Architectures: Alternative Label-Free Immunosensor for Amperometric Immunoassay toward alpha-Fetoprotein. AB - A sensitive, label-free immunosensor based on iridium oxide (IrOx, 0<=x<=2) nanofibers, which were synthesized through a simple one-spinneret electrospinning method, was first developed for immunoassay of the cancer biomarker alpha fetoprotein (AFP). The specific wire-in-tube nanostructure could be obtained and the composition of IrOx nanofibers also could be controlled through changing the annealing temperature. The unique structure and properties of IrOx nanofibers obtained at 500 degrees C not only led to increased electrode surface area and accelerated electron transfer kinetics but also could provide a highly stable matrix for the convenient conjugation of biomolecules together with chitosan (CS). The good electrochemical properties of the IrOx-nanofiber-modified immunosensor allowed one to detect AFP over a wide concentration range from 0.05 to 150 ng/mL, with a detection limit of 20 pg/mL. The proposed immunosensor also has been used to determine AFP in human serum with satisfactory results. The present protocol was shown to be quite promising for clinical screening of cancer biomarkers and point-of-care diagnostics applications. PMID- 26380894 TI - beta-Lactam Resistance Genes: Characterization, Epidemiology, and First Detection of blaCTX-M-1 and blaCTX-M-14 in Salmonella spp. Isolated from Poultry in Brazil Brazil Ministry of Agriculture's Pathogen Reduction Program. AB - Salmonella spp. are widespread in nature; however, human infections occur mainly through ingestion of contaminated food, specially poultry and eggs. In Brazil, the Ministry of Agriculture (MAPA) oversees food production in general, with the goal of preventing transmission of pathogens through the food chain. In 2004, MAPA initiated a program to monitor and control levels of Salmonella in poultry during slaughter. This study analyzes isolates from MAPA's program for beta lactam resistance and the resistance genes involved, as well as the geographic distributions of potentially clonal populations of resistant isolates within Brazil. Initially, 1,939 Salmonella spp. isolated between 2004 and 2011 were examined. These isolates were tested for antimicrobial susceptibility, and 100 isolates resistant or intermediate to ampicillin and ceftriaxone were screened initially for the presence of blaSHV, blaTEM, blaOXA, blaPSA, blaCMY-1, and blaCMY-2 genes. There were 55 isolates whose resistance genes were not identified by this panel and these isolates are the subject of this report. These 55 isolates were differentiated into 31 distinct ribogroups, with multiple beta lactam resistance genes, including AmpC blaCMY, blaTEM, blaCTX-M-1, blaCTX-M-2, blaCTX-M-8, and blaCTX-M-14. Isolates carrying variants of blaCTX-M were identified in three geographic regions. Salmonella carrying particular genetic variants of blaCTX-M and belonging to the same ribogroup were identified from multiple poultry slaughtering facilities. In some instances, these presumptive clonal-related isolates were from facilities over 300 miles apart, indicating potential clonal spread between two geographic regions. This is the first report of blaCTX-M-1 and blaCTX-M-14 in Salmonella in Brazil. PMID- 26380895 TI - Fluoroscopy-guided jejunal extension tube placement through existing gastrostomy tubes: analysis of 391 procedures. AB - PURPOSE: We aimed to evaluate the safety and efficacy of fluoroscopically placed jejunal extension tubes (J-arm) in patients with existing gastrostomy tubes. METHODS: We conducted a retrospective review of 391 J-arm placements performed in 174 patients. Indications for jejunal nutrition were aspiration risk (35%), pancreatitis (17%), gastroparesis (13%), gastric outlet obstruction (12%), and other (23%). Technical success, complications, malfunctions, and patency were assessed. Percutaneous gastrostomy (PEG) tube location, J-arm course, and fluoroscopy time were correlated with success/failure. Failure was defined as inability to exit the stomach. Procedure-related complications were defined as adverse events related to tube placement occurring within seven days. Tube malfunctions and aspiration events were recorded and assessed. RESULTS: Technical success was achieved in 91.9% (95% CI, 86.7%-95.2%) of new tubes versus 94.2% (95% CI, 86.7%-95.2%) of replacements (P = 0.373). Periprocedural complications occurred in three patients (0.8%). Malfunctions occurred in 197 patients (50%). Median tube patency was 103 days (95% CI, 71-134 days). No association was found between successful J-arm placement and gastric PEG tube position (P = 0.677), indication for jejunal nutrition (P = 0.349), J-arm trajectory in the stomach and incidence of malfunction (P = 0.365), risk of tube migration and PEG tube position (P = 0.173), or J-arm length (P = 0.987). A fluoroscopy time of 21.3 min was identified as a threshold for failure. Malfunctions occurred more often in tubes replaced after 90 days than in tubes replaced before 90 days (P < 0.001). A total of 42 aspiration events occurred (OR 6.4, P < 0.001, compared with nonmalfunctioning tubes). CONCLUSION: Fluoroscopy-guided J-arm placement is safe for patients requiring jejunal nutrition. Tubes indwelling for longer than 90 days have higher rates of malfunction and aspiration. PMID- 26380896 TI - MRI features of breast lymphoma: preliminary experience in seven cases. AB - PURPOSE: We aimed to evaluate the imaging features of breast lymphoma using magnetic resonance imaging (MRI). METHODS: This retrospective study consisted of seven patients with pathologically confirmed breast lymphoma. The breast lymphomas were primary in six patients and secondary in one patient. All patients underwent preoperative dynamic contrast-enhanced MRI and one underwent additional diffusion-weighted imaging (DWI) with a b value of 600 s/mm2. Morphologic characteristics, enhancement features, and apparent diffusion coefficient (ADC) values were reviewed. RESULTS: On MRI, three patients presented with a single mass, one with two masses, two with multiple masses, and one with a single mass and a contralateral focal enhancement. The MRI features of the eight biopsied masses in seven patients were analyzed. On MRI, the margins were irregular in six masses (75%) and spiculated in two (25%). Seven masses (87.5%) displayed homogeneous internal enhancement, while one (12.5%) showed rim enhancement. Seven masses (87.5%) showed a washout pattern and one (12.5%) showed a plateau pattern. The penetrating vessel sign was found in two masses (25%). One patient with two masses underwent DWI. Both masses showed hyperintense signal on DWI with ADC values of 0.867*10-3 mm2/s and 0.732*10-3 mm2/s, respectively. CONCLUSION: Breast lymphoma commonly presents as a homogeneously enhancing mass with irregular margins and displays a washout curve pattern on dynamic MRI. A low ADC value may also indicate a possible diagnosis of breast lymphoma. PMID- 26380897 TI - Symptoms seem to be mild in children infected with avian influenza A (H5N6) and other subtypes. PMID- 26380898 TI - Clinical and economic impact of urinary tract infections caused by ESBL-producing Escherichia coli requiring hospitalization: A matched cohort study. AB - OBJECTIVE: To analyze the clinical and economic impact of urinary tract infections (UTIs) caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli requiring hospitalization. METHODS: Matched cohort study including adults with UTI caused by ESBL-producing E. coli admitted to a tertiary care hospital in Barcelona, Spain, between August 2010 and July 2013. Demographic, clinical and economic data were analyzed. RESULTS: One hundred and twenty episodes of UTI were studied: 60 due to ESBL-producing E. coli and 60 due to non-ESBL-producing E. coli. Bivariate analysis showed that prior antimicrobial treatment (p = 0.007) and ESBL production (p < 0.001) were related to clinical failure during the first 7 days. Multivariate analysis selected ESBL as the sole risk factor for clinical failure (p = 0.002). Regarding the economic impact of infections caused by ESBL-producing E. coli, an ESBL-producing infection cost more than a non-ESBL-producing E. coli infection (mean ?4980 vs. ?2612). Looking at hospital expenses separately, the total pharmacy costs and antibiotic costs of ESBL infections were considerably higher than for non-ESBL infections (p < 0.001), as was the need for outpatient parenteral antibiotic therapy (OPAT) and its related costs. Multivariate analysis performed for the higher costs of UTI episodes found statistically significant differences for males (p = 0.004), chronic renal failure (p = 0.025), ESBL production (p = 0.008) and OPAT (p = 0.009). CONCLUSION: UTIs caused by EBSL-producing E. coli requiring hospital admission are associated with worse clinical and economic outcomes. PMID- 26380899 TI - Spatiotemporal patterns of non-genetically modified crops in the era of expansion of genetically modified food. AB - Despite heated debates over the safety of genetically modified (GM) food, GM crops have been expanding rapidly. Much research has focused on the expansion of GM crops. However, the spatiotemporal dynamics of non-genetically modified (non GM) crops are not clear, although they may have significant environmental and agronomic impacts and important policy implications. To understand the dynamics of non-GM crops and to inform the debates among relevant stakeholders, we conducted spatiotemporal analyses of China's major non-GM soybean production region, the Heilongjiang Province. Even though the total soybean planting area decreased from 2005 to 2010, surprisingly, there were hotspots of increase. The results also showed hotspots of loss as well as a large decline in the number and continuity of soybean plots. Since China is the largest non-GM soybean producer in the world, the decline of its major production region may signal the continual decline of global non-GM soybeans. PMID- 26380900 TI - I had a dream.... PMID- 26380901 TI - Toxic effect of aflatoxin B1 and the role of recovery on the rat cerebral cortex and hippocampus. AB - Aflatoxin B1 (AFB1) is the most toxic and well-known mycotoxin that exists in many food stuff. Exposure to AFB1 has been reported to produce serious biochemical and structural alterations in human and animal organs, however, its effect on the brain is not well studied. Therefore, this study was aimed to investigate the possible histopathological effect of AFB1 and its withdrawal on the cerebral cortex and hippocampus. Fifteen adult female Wistar rats were divided into 3 equal groups: control, AFB1 (15.75 MUg/kg/orally, once weekly, for 8 weeks) and recovery groups. Brain sections were processed for hematoxylin and eosin staining as well as for NeuN and GFAP immunostaining. AFB1 administration resulted in several histopathological alterations including; cellular degeneration, dilatation of the blood vessels and significant decrease in the thickness of the frontal cortex and the hippocampal CA1 pyramidal cell layer. In the frontal cortex, there was a significant reduction in the percentage of astrocyte distribution without changes in neuronal numbers. On the other hand, in the hippocampal CA1 region, there was a significant reduction of neuronal number and a significant increase in the percentage of astrocyte distribution. Importantly, AFB1-induced structural alterations were rescued following AFB1 withdrawal. In conclusion, AFB1 induce histological alterations in the rat brain which are potentially reversible upon withdrawal. PMID- 26380902 TI - Facile Access to 5'-S-(4,4'-Dimethoxytrityl)-2',5'-Dideoxyribonucleosides via Stable Disulfide Intermediates. AB - Thionucleosides represent an important class of modified nucleos(t)ides that have found distinct applications in the chemical biology of synthetic oligonucleotides, but the use of these compounds is substantially lessened by the instability or high reactivity of the sulfhydryl group. This unit describes a protocol for the synthesis of 2',5'-dideoxy-5'-thioribonucleoside disulfides by utilizing Mitsunobu reaction conditions on 3'-O-levulinyl-2'-deoxyribonucleosides in the presence of thiobenzoic acid followed by facile hydrolysis and in situ oxidation of the resulting 5'-thiolated nucleosides using methanolic ammonia. The utility of these disulfides has been demonstrated as stable precursors for the synthesis of 5'-thio-modified 2'-deoxynucleosides. To validate the potential of the methodology, 5'-S-(4,4'-dimethoxytrityl)-2',5'-dideoxythymidine phosphoramidite has been synthesized by in situ cleavage of the disulfide linkage of 2',5'-dideoxy-5'-thiothymidine disulfide followed by protection with a dimethoxytriphenyl (DMT) group and 3'-phosphitylation using 2-cyanoethyl N,N diisopropylchlorophosphoramidite. PMID- 26380903 TI - A New Nucleic Acid Prodrug Responsive to High Thiol Concentration: Synthesis of 2'-O-Methyldithiomethyl-Modified Oligonucleotides by Post-Synthetic Modification. AB - This unit describes the synthesis of 2'-O-methyldithiomethyluridine-containing oligonucleotides, which can be deprotected to yield the parental oligoribonucleotides under high concentrations of glutathione similar in cytoplasm. The 2'-O-methyldithiomethyl group is sensitive to reductive conditions, so that it is incompatible to 3'-O-phosphoramidite modification in nucleosides. Thus, a novel post-synthetic approach to obtain 2'-O methyldithiomethyluridine-containing oligonucleotides was developed, in which 2' O-(2,4,6-trimethoxybenzylthiomethyl)uridine-modified oligonucleotides are readily converted by treatment with dimethyl(methylthio)sulfonium tetrafluoroborate to the 2'-O-methyldithiomethyluridine-modified oligonucleotides. The 2'-O methyldithiomethyluridine-modified oligonucleotides are readily and cleanly converted to the parental oligonucleotides under high thiol conditions, such as 10 mM glutathione and dithiothreitol. PMID- 26380904 TI - Native Chemical Ligation of Hydrolysis-Resistant 3'-NH-Cysteine-Modified RNA. AB - Hydrolysis-resistant RNA-peptide conjugates that contain a 3'-NH linkage between the adenosine ribose and the C-terminal carboxyl group of a peptide moiety instead of the natural ester mimic acylated tRNA termini. Their detailed preparation that combines solid-phase oligonucleotide synthesis and bioconjugation is described here. The key step is native chemical ligation (NCL) of 3'-NH-cysteine-modified RNA to highly soluble peptide thioesters. These hydrolysis-resistant 3'-NH-peptide-modified RNAs, containing the universally conserved 3'-CCA end of tRNA, are biologically active and can bind to the ribosome. They can be used as valuable probes for structural and functional studies of the ribosomal elongation cycle. PMID- 26380905 TI - Synthesis of Morpholino Monomers, Chlorophosphoramidate Monomers, and Solid-Phase Synthesis of Short Morpholino Oligomers. AB - Phosphorodiamidate morpholino oligomers (PMOs) are a highly capable class of synthetic antisense oligonucleotides that are used to study gene functions in in vitro and in vivo models. This unit describes the synthesis of exocyclic-amine protected 7'-hydroxy and 7'-chlorophosphoramidate-activated morpholino monomers of A, T, G, and C, together with their incorporation into short PMO oligomers by solid-phase synthesis. Starting from ribonucleosides, the exocyclic-amine protected 7'-hydroxy monomers are prepared following a modified Summerton protocol, which consists of a periodate cleavage/Schiff base formation/reduction cycle. The exocyclic amine protections are installed at a later stage (except G) to avoid the use of costly exocyclic-amine-protected counterparts that give control over protecting group manipulation. The 7'-hydroxy monomers with N-Trit/N MMTr are then converted to the 7'-chlorophosphoramidate morpholino monomers in one step employing a combination of lithium bromide and DBU. These chlorophosphoramidate monomers are finally assembled by solid-support synthesis to obtain the short PMO oligomers. PMID- 26380906 TI - Synthesis of Fluorescent Potassium Ion-Sensing Probes Based on a Thrombin-Binding DNA Aptamer-Peptide Conjugate. AB - This unit provides a procedure for synthesis of the potassium-sensing peptide oligodeoxyribonucleotide conjugate PSO-5 for visualizing potassium ions (K(+) ) in living cells. It is constructed by combining an oligodeoxyribonucleotide carrying a thrombin-binding DNA aptamer (TBA) sequence with an uncharged peptide carrying biotin and the fluorescence tags fluorescein (FAM) and tetramethylrhodamine (TAMRA). The PSO-5 and biotin-modified nuclear export signal peptide are conjugated through streptavidin, and this sensing molecule is introduced into the cell where it is localized in the cytoplasm. The TBA part of PSO-5 shows a conformational change from a random coil to a tetraplex structure induced by K(+) and a change in the fluorescence resonance energy transfer (FRET) efficiency between FAM and TAMRA arising from its conformational change, enabling fluorometric detection of changes in K(+) concentration. PMID- 26380907 TI - [ALLERGEN IMMUNOTHERAPY IN ADULT PATIENTS WITH ALLERGIC DISEASES]. PMID- 26380908 TI - [ALLERGEN IMMUNOTHERAPY IN CHILDREN]. AB - Children are thought to have high plasticity in the immune system. Thus, it is expected that allergen immunotherapy for children may have higher efficacy than adults and has real disease-modifying potential to allergic diseases. For clinical efficacy in ameliorating allergic symptoms, however, current systematic reviews have not shown any superior effect in children, partly because of less number of studies in this age group. On the other hand, preventive effects against asthma inception in children with allergic rhinitis and sensitization "spreading" to new allergens have been reported, implicating that allergen immunotherapy has a potential to stop "allergy march" in children. To make the therapy more effective, it is preferable to start it as early as possible, hopefully in infancy. But it is still difficult at present because of relatively frequent adverse events and invasive manner of administering allergen extracts for young children. We need safer and more effective methods in performing immunotherapy for children. PMID- 26380909 TI - [JAPANESE GUIDELINE FOR FOOD ALLERGY 2012 SPECIFIC TYPE OF FOOD ALLERGY]. PMID- 26380910 TI - [REGULATION OF ANTIBODY RESPONSES BY T FOLLICULAR HELPER CELLS -POTENTIAL ROLE IN IgE PRODUCTION IN ALLERGY]. PMID- 26380911 TI - [ORAL IMMUNOTHERAPY, ITS PRACTICE AND PROBLEMS]. PMID- 26380912 TI - [A CASE OF NATTOU (FERMENTED-SOYBEAN)-INDUCED LATE-ONSET ANAPHYLAXIS FOLLOWING SCUBA DIVING]. AB - We here report a 34-years old male who had nattou-(fermented-soybean) induced late-onset anaphylaxis following SCUBA diving to about 20 m in the ocean off a small remote Japanese island (Kuroshima, Okinawa). He had eaten nattou for breakfast at 7:30 am. He traveled by boat to the dive site, dove twice and then ate lunch at 12:30 on the diving boat (no nattou at lunch). After lunch at 14:30 he dove again (third dive of the day) during which time itchiness started. Back on the diving boat, urticarial was noticed. At 15:30, while washing his diving gear at the diving shop near the harbor, he fainted. A physician arrived on the scene at 15:45. Chest sound was clear and SpO2 was 98%, and blood pressure was 60/- mmHg. Intra-venous hydrocortisone was given, however, his recovery was not satisfactory. Then he was transferred to the Yaeyama Hospital by helicopter at 17:45. The examination of diving computer analysis reveals no sign of increased residual nitrogen, denying the possibility of decompression syndrome. Prick to prick test shows a strongly positive response to nattou. Nattou-induced late onset anaphylaxis following SCUBA diving was suspected. PMID- 26380913 TI - Lumbar spine kinematics during walking in people with and people without low back pain. AB - Low back pain (LBP) is a problem that can contribute to functional limitations and disability. Understanding kinematics during walking can provide a basis for examination and treatment in people with LBP. Prior research related to kinematics during walking is conflicting. However, investigators have not considered regional differences in lumbar spine kinematics or movement-based LBP subgroups. In the current study, three-dimensional kinematics of the upper and lower lumbar regions were examined in people with and without LBP. A clinical examination then was conducted to assign people with LBP to a movement-based subgroup and differences in kinematics among subgroups were examined. All subjects displayed significantly more upper than lower lumbar movement in the axial and coronal planes (P<.01). People with LBP displayed significantly less overall lumbar rotation than controls (P<.05). There were no significant group differences in sagittal plane kinematics (P>.05). Walking was limited by or provocative of pain in <25% of subjects with LBP. There were predictable differences in kinematics among some movement-based LBP subgroups that approached statistical significance (P=.09-.11). Walking was provocative of LBP in few subjects, and differences between people with and without LBP and among LBP subgroups were minimal. Limitations include that attempts to standardize gait speed may have minimized observed effects, and there was limited power to detect movement-based LBP subgroup differences. PMID- 26380914 TI - Latent class analysis of diagnostic tests for adenovirus, Bordetella pertussis and influenza virus infections in German adults with longer lasting coughs. AB - Laboratory tests in adult outpatients with longer lasting coughs to identify a potential causal pathogen are rarely performed, and there is no gold standard for these diagnostic tests. While the diagnostic validity of serological tests for pertussis is well established their potential contribution for diagnosing adenovirus and influenza virus A and B infections is unclear. A sentinel study into the population-based incidence of longer lasting coughs in adults was done in Rostock (former East Germany) and Krefeld (former West Germany). A total of 971 outpatients who consulted general practitioners or internists were included. Inclusion criteria were coughing for ?1 week and no chronic respiratory diseases. We evaluated the performance of polymerase chain reaction (PCR) as well as IgG and IgA serology, applying a latent class model for diagnosing infections with adenovirus, B. pertussis, and influenza virus A and B. The adult outpatients first sought medical attention when they had been coughing for a median of 3 weeks. In this situation, direct detection of infectious agents by PCR had a low sensitivity. Modelling showed that additional serological tests equally improved sensitivity and specificity for diagnosis for adenovirus, B. pertussis and influenza virus A and B infections. The combination of serology and PCR may improve the overall performance of diagnostic tests for B. pertussis and also for adenovirus, and influenza virus A and B infections. PMID- 26380917 TI - IGFBP-1 predicts all-cause mortality in elderly women independently of IGF-I. AB - OBJECTIVE: Previous studies on the insulin-like growth factor (IGF) system and mortality have shown ambiguous results. We investigated the association between IGF-I and insulin- like growth factor binding protein-1 (IGFBP-1) with all-cause mortality in an elderly female Swedish population. DESIGN AND METHODS: A prospective cohort study of elderly women (n=338) aged between 68 and 79 years (mean age 72 years) with a mean follow-up time of 9.9 years. Baseline data in the PRIMOS (Primary Health Care and Osteoporosis) study were collected between 1999 and 2001. Data of risk factors for cardiovascular disease were collected. Death rates were registered from the Swedish Cause of Death register for the period 1999-2009. Cox regression models were used to calculate hazard ratios. IGF-I and IGFBP-1 levels were separately divided into 3 groups (high, medium and low), with cut offs at the 30th and the 70th percentiles. RESULTS: In a fully adjusted Cox proportional hazard model, increased risk of mortality was shown for women with high serum levels of IGFBP-1, HR 3.03 (95% CI 1.64-5.63) and also with low serum levels of IGFBP-1, HR 1.98 (95% CI 1.03-3.81), compared to women with moderate levels. No significant association between IGF-I and mortality was observed. CONCLUSIONS: High and low serum insulin-like IGFBP-1 levels were associated with an increased risk of all-cause mortality in elderly women, compared to moderate levels. PMID- 26380915 TI - Full-length soluble urokinase plasminogen activator receptor down-modulates nephrin expression in podocytes. AB - Increased plasma level of soluble urokinase-type plasminogen activator receptor (suPAR) was associated recently with focal segmental glomerulosclerosis (FSGS). In addition, different clinical studies observed increased concentration of suPAR in various glomerular diseases and in other human pathologies with nephrotic syndromes such as HIV and Hantavirus infection, diabetes and cardiovascular disorders. Here, we show that suPAR induces nephrin down-modulation in human podocytes. This phenomenon is mediated only by full-length suPAR, is time-and dose-dependent and is associated with the suppression of Wilms' tumor 1 (WT-1) transcription factor expression. Moreover, an antagonist of alphavbeta3 integrin RGDfv blocked suPAR-induced suppression of nephrin. These in vitro data were confirmed in an in vivo uPAR knock out Plaur(-/-) mice model by demonstrating that the infusion of suPAR inhibits expression of nephrin and WT-1 in podocytes and induces proteinuria. This study unveiled that interaction of full-length suPAR with alphavbeta3 integrin expressed on podocytes results in down-modulation of nephrin that may affect kidney functionality in different human pathologies characterized by increased concentration of suPAR. PMID- 26380916 TI - The development of a micro-shunt made from poly(styrene-block-isobutylene-block styrene) to treat glaucoma. AB - Glaucoma is the second leading cause of blindness with ~70 million people worldwide who are blind from this disease. The currently practiced trabeculectomy surgery, the gold standard treatment used to stop the progression of vision loss, is rather draconian, traumatic to the patient and requires much surgical skill to perform. This article summarizes the more than 10-year development path of a novel device called the InnFocus MicroShunt(r), which is a minimally invasive glaucoma drainage micro-tube used to shunt aqueous humor from the anterior chamber of the eye to a flap formed under the conjunctiva and Tenon's Capsule. The safety and clinical performance of this device approaches that of trabeculectomy. The impetus to develop this device stemmed from the invention of a new biomaterial called poly(styrene-block-isobutylene-block-styrene), or "SIBS." SIBS is ultra-stable with virtually no foreign body reaction in the body, which manifests in the eye as clinically insignificant inflammation and capsule formation. The quest for an easier, safer, and more effective method of treating glaucoma led to the marriage of SIBS with this glaucoma drainage micro-tube. This article summarizes the development of SIBS and the subsequent three iterations of design and four clinical trials that drove the one-year qualified success rate of the device from 43% to 100%. (c) 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 211-221, 2017. PMID- 26380918 TI - Special Issue: The NYU Silver School of Social Work's Zelda Foster Studies Program: Selected Works from the Leadership Fellowship. Editor's Introduction. PMID- 26380919 TI - The NYU Silver School of Social Work's Zelda Foster Studies Program: Selected Works From the Leadership Fellowship. PMID- 26380920 TI - Building a Bridge to Connect Patients to Their Homeland at End of Life. PMID- 26380921 TI - Cultivating a Culture of Mentorship in Palliative Social Work. PMID- 26380922 TI - Mentoring the Next Generation of Social Workers in Palliative and End-of-Life Care: The Zelda Foster Studies Program. AB - As Americans live longer with chronic illnesses, there is a growing need for social workers with the knowledge and skills to deliver quality palliative care to older adults and their families. Nevertheless, there remains a critical shortage of social workers prepared to provide quality palliative and end-of-life care (PELC) and to maintain the field into the next generation. Formal mentorship programs represent an innovative approach to enhancing practice, providing support and guidance, and promoting social work leadership in the field. This article reviews the literature on mentorship as an approach to professional and leadership development for emerging social workers in PELC. The Zelda Foster Studies Program in Palliative and End-of-Life Care bolsters competencies and mentors social workers in PELC over the trajectory of their careers, and enhances the capacity in the field. Findings from the first six years of two components of the ZF Program are examined to illustrate the feasibility, benefits, and challenges of formal mentorship programs. The authors describe the background, structure, and evaluation of the initiative's mentorship programs, and discuss the implications of mentorship in PELC for social work education, practice, and research. PMID- 26380923 TI - Practicing End-of-Life Conversations: Physician Communication Training Program in Palliative Care. AB - A Physician Communication Training Program (PCTP) utilizing scripts based on actual family conferences with patients, families, and the health care team was developed at one medical center in the Northeast. The program was designed, adapted, and directed by a palliative care social worker. The primary goal of the program is to help residents and attending physicians build better communication skills in establishing goals of care and in end-of-life planning. The scripts focus on improving physicians' basic skills in conducting family meetings, discussing advance directives, prognosis, brain death, and withdrawal of life support. Excerpts from the scripts utilized in the program are included. Feedback from participants has been positive, with all respondents indicating improvement in their capacity to take part in these challenging conversations. PMID- 26380924 TI - Educating Aging Service Agency Staff About Discussing End-of-Life Wishes. AB - Seventy-five percent of Americans support the idea of Advance Directives (ADs) but less than 20% complete one, resulting in increased hospitalization costs, unwanted treatment, and difficult family decisions. Engaging community resources for public education may be effective for increasing understanding and completion of ADs. This project focused on workers in an agency serving older adults. A training program was developed with the goal of increasing their understanding of the process and benefits of Health Care Proxies (HCPs) and ADs through hands-on experience, increasing relevant skills and willingness to discuss with consumers, and to implement an agency protocol increasing documentation of HCPs for consumers. After a small proof-of-concept pilot, all staff members were asked to participate in the educational program. The pilot program delivery found increased staff knowledge as well as motivation to complete HCPs among the staff themselves and their own families. This program resulted in increased staff knowledge of EOL documents, willingness to engage in EOL discussions, and an increase in documented HCPs. This program has relevance for workers in other agencies as they engage older consumers to encourage completion of ADs. This experiential approach to staff education increased their understanding and willingness to initiate EOL discussion with consumers. PMID- 26380925 TI - Palliative Care in Your Nursing Home: Program Development and Innovation in Transitional Care. AB - Each year in the United States, 31% of elders who die do so in hospitals, accounting for over half a million deaths often involving expensive and unnecessary treatments (Zhao & Encinosa, 2010 ). Re-hospitalizations of frail elders with end-stage illnesses are a concern for the hospitals that have discharged them and for the facilities in which they live. In 2011, Schervier Nursing Care Center, a 364-bed skilled nursing and rehabilitation facility in the Bronx, NY, looked at its re-hospitalization rates. It was discovered that a large percentage of the residents being sent to the hospital were from the long-term and subacute populations with end-stage diseases that were no longer responding to treatment. This article describes the development of two innovative programs whose goals were to increase the number of residents receiving palliative care, increase the number of completed advance directives, reduce re-hospitalizations, and increase hospital referrals to the nursing home for palliative care. The key components of both programs and their outcomes are described. The development and implementation of these programs were the author's capstone project for the Zelda Foster Social Work Leadership Fellowship in Palliative and End-of-Life Care. PMID- 26380926 TI - Social Work Practice with LGBT Elders at End of Life: Developing Practice Evaluation and Clinical Skills Through a Cultural Perspective. AB - This article focuses on culturally sensitive clinical issues related to best practices with lesbian, gay, bisexual, transgender (LGBT) elder patients at end of-life (EOL) at key points in the therapeutic relationship. Vital concepts, including practice evaluation and clinical skills, are presented through a cultural and oncology lens. There is a paucity of LGBT research and literature as well as a shortfall of MSW graduate school education specific to social work palliative and end-of-life care (PELC) practice with LGBT elders. The content of this article is designed to be adapted and used as an educational tool for institutions, agencies, graduate programs, medical professions, social work, and students. Learning the unique elements of LGBT cultural history and their implications on EOL care can improve social work practice. This article provides an examination from assessment and engagement basics to advance care planning incorporating specific LGBT EOL issues. PMID- 26380928 TI - Plant protein phosphatases 2C: from genomic diversity to functional multiplicity and importance in stress management. AB - Protein phosphatases (PPs) counteract kinases in reversible phosphorylation events during numerous signal transduction pathways in eukaryotes. Type 2C PPs (PP2Cs) represent the major group of PPs in plants, and recent discovery of novel abscisic acid (ABA) receptors (ABARs) has placed the PP2Cs at the center stage of the major signaling pathway regulating plant responses to stresses and plant development. Several studies have provided deep insight into vital roles of the PP2Cs in various plant processes. Global analyses of the PP2C gene family in model plants have contributed to our understanding of their genomic diversity and conservation, across plant species. In this review, we discuss the genomic and structural accounts of PP2Cs in plants. Recent advancements in their interaction paradigm with ABARs and sucrose nonfermenting related kinases 2 (SnRK2s) in ABA signaling are also highlighted. In addition, expression analyses and important roles of PP2Cs in the regulation of biotic and abiotic stress responses, potassium (K+) deficiency signaling, plant immunity and development are elaborated. Knowledge of functional roles of specific PP2Cs could be exploited for the genetic manipulation of crop plants. Genetic engineering using PP2C genes could provide great impetus in the agricultural biotechnology sector in terms of imparting desired traits, including a higher degree of stress tolerance and productivity without a yield penalty. PMID- 26380929 TI - Genetic Polymorphism and Messenger Ribonucleic Acid Concentrations of TNFalpha and TGFbeta Genes in Patients with Chronic Lower Limb Infections. AB - BACKGROUND: The number of chronic lower limb infections and their complications as venous and diabetic ulcers and chronic calf dermatitis is increasing worldwide. The clinical course and outcome in the immune responses to infection have been shown to be associated with genetic polymorphisms. The aim of study was to investigate frequencies of chosen single nucleotide polymorphisms (SNPs) in TNFalpha and TGFbeta genes in patients with chronic lower limb infections and evaluate expression of messenger ribonucleic acid (mRNA) concentrations in chronic leg ulcers. METHODS: Patients were divided into three groups: (group A) chronic venous leg ulcers, (group B) chronic post-traumatic non-healing wounds, and (group C) infected ischemic necrosis of the foot. Blood donors comprised the control group. Detection of polymorphisms was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and gene expression by real-time PCR methods. RESULTS: Patients in all groups showed higher frequency of TNFalpha gene polymorphism -308GG and lower frequency of -308GA genotypes than controls. The mutated homozygote AA was higher in groups A and B than in controls. The TGFbeta74GG genotype was represented at highest values in group B. The GC genotype was found in all groups at a similar concentration lower than in controls. Genotypes TGFbeta29TT and TC were represented at similar concentrations as controls. Analyses showed that the presence of the polymorphic allele -308A of TNFalpha gene was correlated with an increased concentration of gene expression in patients with chronic leg ulcers (group A). In the case of both TGFbeta gene polymorphisms the presence of polymorphic allele C resulted in increased TGFbeta gene expression. CONCLUSIONS: Comparison of genotypes in polymorphic sites in TNFalpha and TGFbeta genes with their expression concentrations showed that the presence of polymorphic alleles could predispose to increased production of their proteins. Patients with prolonged non-healing wounds should have their genotypes studied, and in cases of mutation, long-term antibiotic and immune protein supply should be considered. PMID- 26380927 TI - Serum exosomal microRNAs as novel biomarkers for hepatocellular carcinoma. AB - Recent studies have shown that circulating microRNAs are a potential biomarker in various types of malignancies. The aim of this study was to investigate the feasibility of using serum exosomal microRNAs as novel serological biomarkers for hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). We measured the serum exosomal microRNAs and serum circulating microRNAs in patients with CHB (n=20), liver cirrhosis (LC) (n=20) and HCC (n=20). Serum exosomal microRNA was extracted from 500 MUl of serum using an Exosome RNA Isolation kit. The expression levels of microRNAs were quantified by real-time PCR. The expression levels of selected microRNAs were normalized to Caenorhabditis elegans microRNA (Cel-miR-39). The serum levels of exosomal miR-18a, miR-221, miR-222 and miR-224 were significantly higher in patients with HCC than those with CHB or LC (P<0.05). Further, the serum levels of exosomal miR-101, miR-106b, miR-122 and miR-195 were lower in patients with HCC than in patients with CHB (P=0.014, P<0.001, P<0.001 and P<0.001, respectively). There was no significant difference in the levels of miR-21 and miR-93 among the three groups. Additionally, the serum levels of circulating microRNAs showed a smaller difference between HCC and either CHB or LC. This study suggests that serum exosomal microRNAs may be used as novel serological biomarkers for HCC. PMID- 26380930 TI - Designing alpha-helical peptides with enhanced synergism and selectivity against Mycobacterium smegmatis: Discerning the role of hydrophobicity and helicity. AB - Recently, we reported on a series of short amphipathic alpha-helical peptides, comprising the backbone sequence (LLKK)2, with the ability to kill susceptible and drug-resistant Mycobacterium tuberculosis. In this study, the effect of key physicochemical parameters including hydrophobicity and helicity of alpha-helical peptides on anti-mycobacterial activity and synergism with rifampicin was investigated. The most hydrophobic analogue, W(LLKK)2W, displayed low selectivity against mycobacteria while peptides with intermediate hydrophobicity were shown to be equally active, yet significantly less toxic. Furthermore, proline substitution impeded the formation of stable amphipathic structures, rendering P(LLKK)2P as one of the least active analogues. Terminal capping with isoleucine was found to promote alpha-helical folding and the resultant peptide demonstrated the highest selectivity and minimal cytotoxicity against mammalian macrophages. Flow cytometric analysis revealed that enhancements in hydrophobicity and alpha helicity increased the rate and extent of peptide-mediated membrane permeabilization. This finding corroborated the hypothesis that synergism between the peptides and rifampicin was likely mediated via peptide-induced pore formation. The rapid, concentration-dependent membrane depolarization, leakage of intracellular ATP and calcein release from PE/PG LUVs supported the membrane lytic mechanism of action of the peptides. Together, these findings suggest that hydrophobicity and alpha-helicity significantly impact anti-mycobacterial activity and optimization of both parameters is necessary to develop synthetic analogues with superior selectivity indices and enhanced synergistic potential with conventional antibiotics. STATEMENT OF SIGNIFICANCE: There is an urgent clinical need for the discovery of new antimicrobials, effective not just for drug susceptible, but also rapidly emerging drug-resistant TB. Recently, we reported on a series of short amphipathic alpha-helical peptides, comprising the backbone sequence (LLKK)2, with the ability to kill susceptible and drug resistant M. tuberculosis. In this study, we evaluated a series of synthetic alpha-helical (LLKK)2 peptides over a range of hydrophobicities for their activity against mycobacteria and provide the first report on the modulating effect of hydrophobicity and alpha-helicity on the antimicrobial mechanisms of synthetic AMPs and their synergism with first-line antibiotics. These findings demonstrate the applicability of strategies employed here for the rational design of AMPs with the aim of improving cell selectivity and synergistic interactions when co-administered with first-line antibiotics in the fight against drug resistant tuberculosis. PMID- 26380932 TI - C3 functionalization of indolizines via In(iii)-catalyzed three-component reaction. AB - Post-functionalization at the C3 position of indolizines via In(iii)-catalyzed three-component coupling reaction with amines and aldehydes allowed rapid access to a new class of indolizines with diverse functional groups at the C3 position in good to excellent yields. PMID- 26380931 TI - Synoptic operative reports enhance documentation of best practices for rectal cancer. AB - BACKGROUND: Implementation of best practices surgical checklists improves patient safety and outcomes. However, documenting performance of these practices can be challenging. The American Society of Colon and Rectal Surgeons developed a Best Practices for Rectal Cancer Checklist (RCC) to standardize and improve the quality of rectal cancer surgery. This study compared the degree to which synoptic (SR) and narrative (NR) operative reports document RCC items. METHODS: Two reviewers independently reviewed a cohort of prospectively collected SR for rectal cancer surgery and a case-matched historical cohort of NR. Reports were reviewed for documentation of performance of operative items on the RCC. Abstraction time and inter-rater agreement were also measured. RESULTS: SR scored significantly higher than NR on the overall checklist score (mean adjusted score +/- standard deviation 12.4 +/- 0.9 vs. 5.7 +/- 1.9, maximum possible score 18, P < 0.001). Reviewers abstracted data significantly faster from SR. Inter-rater agreement between reviewers was high for both types of reports. CONCLUSIONS: SR were associated with reliable and more complete and reliable documentation of items on the RCC. Use of an SR system standardizes operative reporting, providing the opportunity to enhance checklist compliance, and enable timely feedback to improve surgical outcomes for rectal cancer patients. PMID- 26380933 TI - Electrical transport properties of AlAs under compression: reversible boundary effect. AB - Herein, we report on the intriguing electrical transport properties of compressed AlAs. The relative permittivity and the resistances of both the grain and bulk boundaries vary abnormally at ~10.9 GPa, accompanied by the cubic-hexagonal structural transition of AlAs. With further compression, the boundary effect becomes undistinguished, and subsequently, the electrical transport mechanism converts from boundary- to bulk-dominated, which gives rise to a significant reduction in the total resistance of AlAs. After being quenched to ambient pressure, resistances recover to the initial values followed by the re-emergence of the boundary effect. Eg decreases with pressure and its pressure dependence changes at ~14.0 GPa, which rationalizes the anomalous variation of the electrical transport properties. The experimental results indicate that the boundary effect can be modulated by compression and increases the resistance difference between the two states. This opens up a new possible basis for optimizing the performance of AlAs-based applications, including multilevel phase change memories. PMID- 26380934 TI - Filling in the Acupuncture Jigsaw Puzzle. PMID- 26380935 TI - Toward a Neuroimmunoendocrinology of Adipose Tissue. PMID- 26380936 TI - Long-Lasting Consequences of Testosterone Exposure. PMID- 26380937 TI - It Takes Two Gonadotropins to Tango in Zebrafish But With a Mixed Tune. PMID- 26380938 TI - Insights Into the Progression of beta-Cell Dysfunction Caused by Preterm Birth. PMID- 26380941 TI - Using Peptide-Level Proteomics Data for Detecting Differentially Expressed Proteins. AB - The expression of proteins can be quantified in high-throughput means using different types of mass spectrometers. In recent years, there have emerged label free methods for determining protein abundance. Although the expression is initially measured at the peptide level, a common approach is to combine the peptide-level measurements into protein-level values before differential expression analysis. However, this simple combination is prone to inconsistencies between peptides and may lose valuable information. To this end, we introduce here a method for detecting differentially expressed proteins by combining peptide-level expression-change statistics. Using controlled spike-in experiments, we show that the approach of averaging peptide-level expression changes yields more accurate lists of differentially expressed proteins than does the conventional protein-level approach. This is particularly true when there are only few replicate samples or the differences between the sample groups are small. The proposed technique is implemented in the Bioconductor package PECA, and it can be downloaded from http://www.bioconductor.org. PMID- 26380942 TI - Pharmacological study of direction selectivity in the archer fish retina. AB - Direction selective cells have been found in the retina, the first level of the visual system, in mammals and recently also in the archer fish. These cells are involved in a variety of fast neural computation processes, from the control of eye movements to the detection of prey by the archer fish. The standard model for this mechanism in mammalian retina is well understood and is based on the asymmetry of inhibitory and excitatory inputs to the retinal ganglion cells. However, it remains unclear whether the mechanism that underlies direction selectivity is similar across animal classes. This study reports a pharmacological investigation designed to elucidate the mechanism that underlies motion detection in the archer fish retina. Direction selectivity in the retina was characterized under the influence of specific channel blockers that are known to be present in the different types of neurons of the retina. The results show that the direction-selective mechanism in the archer fish retina is modified only when the inhibitory channels of GABA and Glycine are manipulated. This suggests that the mechanism of direction selectivity in the archer fish retina is fundamentally different from the mechanism of direction selectivity in the mammalian retina. PMID- 26380943 TI - Suppressed phase transition and giant ionic conductivity in La2Mo2O9 nanowires. AB - Improving the ionic conductivity of solid electrolytes at low temperatures represents a major challenge and an opportunity for enabling a variety of solid state ionic devices for energy conversion and storage, as well as for environmental protection. Here we report a giant ionic conductivity of 0.20 Scm( 1), achieved at 500 degrees C, in the La2Mo2O9 nanowires with a bamboo-wire morphology, corresponding to a 1000-fold enhancement in conductivity over conventional bulk material. Stabilization of the high-temperature phase is observed to account for about a 10-fold increase in the conductivity. We further demonstrate that fast surface conduction in ~3 nm thick, partially ordered, surface 'amorphous' films, under strain on the curved surfaces of the nanowires (as a non-autonomous surface phase or complexion), contributes to an enhancement of the conductivity by another two orders of magnitude. Exemplified here by the study of the La2Mo2O9 nanowires, new possibilities for improvement of conductivity and for miniaturization of solid-state ionic devices by the careful use of one-dimensional nanomaterials can be envisioned. PMID- 26380944 TI - Minimal clinically important difference and Edmonton Symptom Assessment Scale. PMID- 26380946 TI - Serological detection of infection dynamics for respiratory viruses among dairy calves. AB - The aim of this study is to reveal infection dynamics of bovine respiratory syncytial virus (BRSV), bovine parainfluenza virus type 3 (PI-3), bovine herpesvirus 1 (BHV-1), bovine viral diarrhea virus (BVDV), bovine adenovirus type 3 (BAV-3) and bovine coronavirus (BCoV), which are important viral pathogens of respiratory disease complex in ruminants. Through such an analysis, the regression period of maternally derived antibodies and optimum vaccination time in calves can be recommended. A total of 10 farms were grouped as large (4)-, medium (2)- and small (4)- sized enterprises according to their animal population. Newborn calves (n: 94) delivered during a calendar month on the farms were studied. Blood samples were collected from these calves during their 1st, 2nd, 3rd, 4th, 6th, 8th, 10th and 12th months of age. Blood samples were also taken from their dams during the first sampling. Neutralizing antibody titers were detected using the serum neutralization test (SN50). New PI-3 and BVDV infections at the early stages of life were determined in the calves. Maternal antibodies began to decrease in the 2nd month for BRSV, BHV-1 and BAV-3 (97.8%, 25.5% and 91.4%) and in the 3rd month for PI-3, BVDV and BCoV (85.1%, 67% and 93.6%). It was concluded that maternal antibodies begin to decrease after the 1st month and that the possible first exposure of calves to respiratory viruses is after the 2nd month. Therefore, it is recommended that the first vaccination program including prime and booster doses can be applied between 2 and 4 months of age. Furthermore, re-vaccination of animals at 6 months after the booster dose is also suggested. PMID- 26380945 TI - The ubiquitin ligase Siah2 regulates obesity-induced adipose tissue inflammation. AB - OBJECTIVE: Chronic, low-grade adipose tissue inflammation associated with adipocyte hypertrophy is an important link in the relationship between obesity and insulin resistance. Although ubiquitin ligases regulate inflammatory processes, the role of these enzymes in metabolically driven adipose tissue inflammation is relatively unexplored. Herein, the effect of the ubiquitin ligase Siah2 on obesity-related adipose tissue inflammation was examined. METHODS: Wild type and Siah2KO mice were fed a low- or high-fat diet for 16 weeks. Indirect calorimetry, body composition, and glucose and insulin tolerance were assayed along with glucose and insulin levels. Gene and protein expression, immunohistochemistry, adipocyte size distribution, and lipolysis were also analyzed. RESULTS: Enlarged adipocytes in obese Siah2KO mice were not associated with obesity-induced insulin resistance. Proinflammatory gene expression, stress kinase signaling, fibrosis, and crown-like structures were reduced in the Siah2KO adipose tissue, and Siah2KO adipocytes were more responsive to insulin-dependent inhibition of lipolysis. Loss of Siah2 increased expression of PPARgamma target genes involved in lipid metabolism and decreased expression of proinflammatory adipokines regulated by PPARgamma. CONCLUSIONS: Siah2 links adipocyte hypertrophy with adipocyte dysfunction and recruitment of proinflammatory immune cells to adipose tissue. Selective regulation of PPARgamma activity is a Siah2-mediated mechanism contributing to obesity-induced adipose tissue inflammation. PMID- 26380947 TI - Assessment and treatment of pica and destruction of holiday decorations. AB - Problem behavior exhibited by individuals with autism can be disruptive to family traditions, such as decorating for the holidays. We present data for a 6-year-old girl who engaged in automatically reinforced pica and destruction of holiday decorations. Treatment was evaluated within an ABCDCD reversal design. During baseline (Phases A and B), we observed elevated rates of problem behavior. We implemented differential reinforcement of alternative behavior in Phase C to teach a response to compete with problem behavior. Little change in toy play or problem behavior occurred. In Phase D, we added a facial screen to the differential reinforcement procedures, which resulted in increases in toy play and decreases in problem behavior. Findings are discussed in terms of how interventions for problem behavior can promote alternative behavior while they facilitate household activities and traditions. PMID- 26380948 TI - The Hubbard dimer: a density functional case study of a many-body problem. AB - This review explains the relationship between density functional theory and strongly correlated models using the simplest possible example, the two-site Hubbard model. The relationship to traditional quantum chemistry is included. Even in this elementary example, where the exact ground-state energy and site occupations can be found analytically, there is much to be explained in terms of the underlying logic and aims of density functional theory. Although the usual solution is analytic, the density functional is given only implicitly. We overcome this difficulty using the Levy-Lieb construction to create a parametrization of the exact function with negligible errors. The symmetric case is most commonly studied, but we find a rich variation in behavior by including asymmetry, as strong correlation physics vies with charge-transfer effects. We explore the behavior of the gap and the many-body Green's function, demonstrating the 'failure' of the Kohn-Sham (KS) method to reproduce the fundamental gap. We perform benchmark calculations of the occupation and components of the KS potentials, the correlation kinetic energies, and the adiabatic connection. We test several approximate functionals (restricted and unrestricted Hartree-Fock and Bethe ansatz local density approximation) to show their successes and limitations. We also discuss and illustrate the concept of the derivative discontinuity. Useful appendices include analytic expressions for density functional energy components, several limits of the exact functional (weak- and strong-coupling, symmetric and asymmetric), various adiabatic connection results, proofs of exact conditions for this model, and the origin of the Hubbard model from a minimal basis model for stretched H2. PMID- 26380949 TI - Solid-state reaction as a mechanism of 1T <-> 2H transformation in MoS2 monolayers. AB - Monolayers of molybdenum disulfide MoS2 are considered to be prospective materials for nanoelectronics and various catalytic processes. Since in certain conditions they undergo 1T <-> 2H phase transitions, studying these phase changes is an urgent task. We present a DFT research of these transitions to show that they can proceed as a solid-state reaction. Two transition states were discovered with energy barriers 1.03 and 1.40 eV. Sulfur atoms in the transition states are shown to be displaced relative to molybdenum atoms so that a tendency of one structural modification to transform into the other modification is seen. This kind of displacements agrees with electron microscopy data reported earlier. The energy parameters indicate that 1T -> 2H reactions are exothermic for both transition states and can possibly proceed in a self-sustained manner when initially activated by some external energy impact. PMID- 26380950 TI - The influence of GAP-43 on orientation of cell division through G proteins. AB - Recent studies have shown that GAP-43 is highly expressed in horizontally dividing neural progenitor cells, and G protein complex are required for proper mitotic-spindle orientation of those progenitors in the mammalian developing cortex. In order to verify the hypothesis that GAP-43 may influence the orientation of cell division through interacting with G proteins during neurogenesis, the GAP-43 RNA from adult C57 mouse was cloned into the pEGFP-N1 vector, which was then transfected into Madin-Darby Canine Kidney (MDCK) cells cultured in a three-dimensional (3D) cell culture system. The interaction of GAP 43 with Galphai was detected by co-immunoprecipitation (co-IP), while cystogenesis of 3D morphogenesis of MDCK cells and expression of GAP-43 and Galphai were determined by immunofluorescence and Western blotting. The results showed are as follows: After being transfected by pEGFP-N1-GAP-43, GAP-43 was localized on the cell membrane and co-localized with Galphai, and this dramatically induced a defective cystogenesis in 3D morphogenesis of MDCK cells. The functional interaction between GAP-43 and Galphai proteins was proven by the co-IP assay. It can be considered from the results that the GAP-43 is involved in the orientation of cell division by interacting with Galphai and this should be an important mechanism for neurogenesis in the mammalian brain. PMID- 26380952 TI - Redefining the Recreational Drug User Population in Human Abuse Potential Studies. PMID- 26380951 TI - Striatal and Cortical beta-Amyloidopathy and Cognition in Parkinson's Disease. AB - INTRODUCTION: Although most previous cognitive studies of beta-amyloidopathy in PD focused on cortical plaque deposition, recent postmortem studies point to an important role of striatal beta-amyloid plaque deposition. The aim of this study was to investigate the relative contributions of striatal and cortical beta amyloidopathy to cognitive impairment in PD. METHODS: Patients with PD (n = 62; age, 68.9 +/- 6.4 years; H & Y stage: 2.7 +/- 0.5; MoCA score: 25.2 +/- 3.0) underwent [(11) C]Pittsburgh compound B beta-amyloid, [(11) C]dihydrotetrabenazine monoaminergic, and [(11) C]methyl-4-piperidinyl propionate acetylcholinesterase brain PET imaging and neuropsychological assessment. [(11) C]Pittsburgh compound B beta-amyloid data from young to middle-aged healthy subjects were used to define elevated [(11) C]Pittsburgh compound B binding in patients. RESULTS: Elevated cortical and striatal beta-amyloid deposition were present in 37% and 16%, respectively, of this predominantly nondemented cohort of patients with PD. Increased striatal beta-amyloid deposition occurred in half of all subjects with increased cortical beta-amyloid deposition. In contrast, increased striatal beta-amyloid deposition did not occur in the absence of increased cortical beta-amyloid deposition. Analysis of covariance using global composite cognitive z scores as the outcome parameter showed significant regressor effects for combined striatal and cortical beta-amyloidopathy (F = 4.18; P = 0.02) after adjusting for covariate effects of cortical cholinergic activity (F = 5.67; P = 0.02), caudate nucleus monoaminergic binding, duration of disease, and age (total model: F = 3.55; P = 0.0048). Post-hoc analysis showed significantly lower cognitive z score for combined striatal and cortical beta amyloidopathy, compared to cortical-only beta-amyloidopathy and non-beta amyloidopathy subgroups. CONCLUSIONS: The combined presence of striatal and cortical beta-amyloidopathy is associated with greater cognitive impairment than cortical beta-amyloidopathy alone in PD. PMID- 26380953 TI - Distinctive Capillary Action by Micro-channels in Bone-like Templates can Enhance Recruitment of Cells for Restoration of Large Bony Defect. AB - Without an active, thriving cell population that is well-distributed and stably anchored to the inserted template, exceptional bone regeneration does not occur. With conventional templates, the absence of internal micro-channels results in the lack of cell infiltration, distribution, and inhabitance deep inside the templates. Hence, a highly porous and uniformly interconnected trabecular-bone like template with micro-channels (biogenic microenvironment template; BMT) has been developed to address these obstacles. The novel BMT was created by innovative concepts (capillary action) and fabricated with a sponge-template coating technique. The BMT consists of several structural components: inter connected primary-pores (300-400 um) that mimic pores in trabecular bone, micro channels (25-70 um) within each trabecula, and nanopores (100-400 nm) on the surface to allow cells to anchor. Moreover, the BMT has been documented by mechanical test study to have similar mechanical strength properties to those of human trabecular bone (~3.8 MPa)12. The BMT exhibited high absorption, retention, and habitation of cells throughout the bridge-shaped (Pi) templates (3 cm height and 4 cm length). The cells that were initially seeded into one end of the templates immediately mobilized to the other end (10 cm distance) by capillary action of the BMT on the cell media. After 4 hr, the cells homogenously occupied the entire BMT and exhibited normal cellular behavior. The capillary action accounted for the infiltration of the cells suspended in the media and the distribution (active migration) throughout the BMT. Having observed these capabilities of the BMT, we project that BMTs will absorb bone marrow cells, growth factors, and nutrients from the periphery under physiological conditions. The BMT may resolve current limitations via rapid infiltration, homogenous distribution and inhabitance of cells in large, volumetric templates to repair massive skeletal defects. PMID- 26380954 TI - Pri-miR-34b/c rs4938723 polymorphism contributes to acute lymphoblastic leukemia susceptibility in Chinese children. AB - A polymorphism rs4938723 (T > C) within the promoter region of pri-miR-34b/c has been found to not only affect the expression of mature miR-34b/c but also contribute to the susceptibility to several cancer types. We designed a case control study to evaluate the role of rs4938723 in childhood acute lymphoblastic leukemia (ALL). The rs4938723 CC genotype was significantly associated with reduced ALL risk (p = 0.003, ORadjusted = 0.51, 95% CI = 0.33-0.80 for CC vs. TT). Stratification analyses showed the differences were pronounced in older (> 6 years), male subjects, as well as in patients in low risk and T-ALL subtypes. The in vitro luciferase assays in Jurkat and K-562 cell lines showed that the transcription activity of miR-34b/c was increased when T allele transited to C allele (p < 0.05). In conclusion, rs4938723 genetic variant contributed to the susceptibility to Chinese childhood ALL by influencing the transcription activity of miR-34b/c promoter. PMID- 26380955 TI - Fracture Load Before and After Veneering Zirconia Posterior Fixed Dental Prostheses. AB - PURPOSE: To evaluate the fracture load of 3-unit zirconia-based posterior fixed dental prostheses (FDPs) before and after veneering the frameworks. MATERIALS AND METHODS: Forty standardized stainless-steel master dies were fabricated (height: 5 mm, convergence: 6o, chamfer: 1 mm) and randomly screwed in pairs onto metal bases. The bases were randomly divided into two groups (n = 20 each) according to the zirconia CAD/CAM system used for constructing 3-unit structures for FDPs: group 1 (L): Lava All-ceramic, group 2 (Z): IPS e.max ZirCAD. Half of the zirconia structures per group were randomly selected and veneered, while the remaining half was left unveneered. The specimens were luted in standard fashion onto the stainless steel master dies using conventional glass ionomer cement. All specimens were tested for fracture load (FL). Specimens were subjected to a three point bending test until fracture by applying an axial compressive load at the central fossa of the pontics with a universal testing machine at a 0.5 mm/min crosshead speed. Wilcoxon's rank-sum test and Weibull statistics were used for statistical analysis (alpha = 0.05). RESULTS: L structures recorded significantly higher values of load to fracture than the Z group both before and after veneering. Within each ceramic group, no differences were found between unveneered and veneered frameworks. CONCLUSIONS: Although further studies are necessary to corroborate these findings, both zirconia systems could be recommended for restoring posterior teeth on the basis of the fracture load values recorded in this experiment (>1000 N). The veneering procedure did not affect the overall load to fracture in any group. PMID- 26380956 TI - Site selective syntheses of [(3)H]omeprazole using hydrogen isotope exchange chemistry. AB - Omeprazole (Prilosec(r)) is a selective and irreversible proton pump inhibitor used to treat various medical conditions related to the production of excess stomach acids. It functions by suppressing secretion of those acids. Radiolabeled compounds are commonly employed in the drug discovery and development process to support efforts including library screening, target identification, receptor binding, assay development and validation and safety assessment. Herein, we describe synthetic approaches to the controlled and selective labeling of omeprazole with tritium via hydrogen isotope exchange chemistry. The chemistry may also be used to prepare tritium labeled esomeprazole (Nexium(r)), the active pure (S)-enantiomer of omeprazole. PMID- 26380958 TI - Stress urinary incontinence and endogenous sex steroids in postmenopausal women. AB - AIMS: Urinary incontinence in general is a major cause of quality of life impairment, morbidity and hospitalization. Its onset is strongly linked to the menopause. Our study aimed to elucidate the possible relationship between endogenous circulating estrogens and the onset and development of stress urinary incontinence (SUI). METHODS: One hundred and thirty eight peri- and postmenopausal women with SUI were matched 1:1 with continent women based on age and BMI. Morning fasting blood samples were drawn from all subjects for assessment of estradiol (E2), FSH, LH, Testosterone, Delta4-Androstendione (Delta4Alpha), DHEAS, prolactin, SBHG as well as a biochemical profile (glucose, insulin, triglycerides, cholesterol, HDL, LDL, ApoA1, ApoB). Hormone and biochemical parameters were compared between continent and incontinent women. RESULTS: Incontinent women had significantly lower serum estradiol levels compared to those in the control group (17.30 +/- 8.16 vs. 24.22 +/- 8.99, P < 0.001). Furthermore, the same association was observed for serum Delta4Alpha (146.07 +/- 52.63 vs. 159.99 +/- 42.62, P = 0.017). These associations remained significant after controlling for age, menopausal age, BMI, and number of deliveries. CONCLUSIONS: These results may indicate that within the postmenopausal range, endogenous sex hormones may be associated with the presence of SUI in women not on menopausal hormone therapy. Neurourol. Urodynam. 36:121 125, 2017. (c) 2015 Wiley Periodicals, Inc. PMID- 26380957 TI - Chronic Alcohol Exposure Enhances Lipopolysaccharide-Induced Lung Injury in Mice: Potential Role of Systemic Tumor Necrosis Factor-Alpha. AB - BACKGROUND: It is well known that liver and lung injury can occur simultaneously during severe inflammation (e.g., multiple organ failure). However, whether these are parallel or interdependent (i.e., liver-lung axis) mechanisms is unclear. Previous studies have shown that chronic ethanol (EtOH) consumption greatly increases mortality in the setting of sepsis-induced acute lung injury (ALI). The potential contribution of subclinical liver disease in driving this effect of EtOH on the lung remains unknown. Therefore, the purpose of this study was to characterize the impact of chronic EtOH exposure on concomitant liver and lung injury. METHODS: Male mice were exposed to EtOH-containing Lieber-DeCarli diet or pair-fed control diet for 6 weeks. Some animals were administered lipopolysaccharide (LPS) 4 or 24 hours prior to sacrifice to mimic sepsis-induced ALI. Some animals received the tumor necrosis factor-alpha (TNF-alpha)-blocking drug, etanercept, for the duration of alcohol exposure. The expression of cytokine mRNA in lung and liver tissue was determined by quantitative PCR. Cytokine levels in the bronchoalveolar lavage fluid and plasma were determined by Luminex assay. RESULTS: As expected, the combination of EtOH and LPS caused liver injury, as indicated by significantly increased levels of the transaminases alanine aminotransferase/aspartate aminotransferase in the plasma and by changes in liver histology. In the lung, EtOH preexposure enhanced pulmonary inflammation and alveolar hemorrhage caused by LPS. These changes corresponded with unique alterations in the expression of pro-inflammatory cytokines in the liver (i.e., TNF-alpha) and lung (i.e., macrophage inflammatory protein-2 [MIP-2], keratinocyte chemoattractant [KC]). Systemic depletion of TNF-alpha (etanercept) blunted injury and the increase in MIP-2 and KC caused by the combination of EtOH and LPS in the lung. CONCLUSIONS: Chronic EtOH preexposure enhanced both liver and lung injury caused by LPS. Enhanced organ injury corresponded with unique changes in the pro-inflammatory cytokine expression profiles in the liver and the lung. PMID- 26380959 TI - One-Step Borylation of 1,3-Diaryloxybenzenes Towards Efficient Materials for Organic Light-Emitting Diodes. AB - The development of a one-step borylation of 1,3-diaryloxybenzenes, yielding novel boron-containing polycyclic aromatic compounds, is reported. The resulting boron containing compounds possess high singlet-triplet excitation energies as a result of localized frontier molecular orbitals induced by boron and oxygen. Using these compounds as a host material, we successfully prepared phosphorescent organic light-emitting diodes exhibiting high efficiency and adequate lifetimes. Moreover, using the present one-step borylation, we succeeded in the synthesis of an efficient, thermally activated delayed fluorescence emitter and boron-fused benzo[6]helicene. PMID- 26380960 TI - Ectopic gastric mucosal ulcer of the jejunum without congenital anomaly causing intestinal obstruction. PMID- 26380961 TI - Gd2Cu(SO4)2(OH)4: a 3d-4f hydroxysulfate with an enhanced cryogenic magnetocaloric effect. AB - A 3d-4f hydroxysulfate, Gd2Cu(SO4)2(OH)4, is synthesized by means of a conventional hydrothermal method. Magnetic measurements confirm that the title compound exhibits a paramagnetic behavior down to 2 K, in which an enhanced magnetocaloric effect with a maximum -DeltaSm (45.52(1) J kg(-1) K(-1), 212.8(6) mJ cm(-3) K(-1)) is observed at ~4 K for DeltaH = 8 T. The thermal stability using TG analysis and a FT-IR spectrum are also investigated. PMID- 26380962 TI - Green synthesis of carbon-supported nanoparticle catalysts by physical vapor deposition on soluble powder substrates. AB - Metal and metal oxide nanoparticles (NPs) supported on high surface area carbon (NP/Cs) were prepared by the physical vapor deposition of bulk materials on an alpha-D-glucose (Glu) substrate, followed by the deposition of the NPs on carbon supports. Using Glu as a carrier for the transport of NPs from the bulk materials to the carbon support surfaces, ultrafine NPs were obtained, exhibiting a stabilizing effect through OH moieties on the Glu surfaces. This stabilizing effect was strong enough to stabilize the NPs, but weak enough to not significantly block the metal surfaces. As only the target materials and Glu are required in our procedure, it can be considered environmentally friendly, with the NPs being devoid of hazardous chemicals. Furthermore, the resulting NP/Cs exhibited an improvement in activity for various electrochemical reactions, mainly attributed to their high surface area. PMID- 26380963 TI - Appropriateness of care and moral distress among neonatal intensive care unit staff: repeated measurements. AB - BACKGROUND: Perceived constraints to providing patient care in their own morally justified way may cause moral distress (MD) in neonatal nurses and physicians. Negative long-term effects of MD include substandard patient care, burnout and leaving the profession. AIM: To assess the immediate impact of perceived inappropriate patient care on nurses' and physicians' MD intensity, and explore a possible moderating effect of ethical climate. DESIGN: In a repeated measures design, after baseline assessment, each participant completed self-report questionnaires after five randomly selected shifts. Data were analysed with logistic and Tobit regression. PARTICIPANTS: Data were collected among 117 of 147 eligible nurses and physicians (80%) in a level-III neonatal intensive care unit in the Netherlands. RESULTS: At baseline, overall MD was relatively low; in nurses, it was significantly higher than in physicians. Few morally distressing situations were reported in the repeated measurements, but distress could be intense in these cases; nurses' and physicians' scores were comparable. Physicians were significantly more likely than nurses to disagree with their patients' level of care (p = 0.02). Still, perceived overtreatment, but not undertreatment, was significantly related to distress intensity in both professional groups; ethical climate did not moderate this effect. Substandard patient care due to lack of continuity, poor communication and unsafe levels of staffing were rated as more important causes of MD than perceived inappropriate care. CONCLUSIONS: Although infrequently perceived, overtreatment of patients caused considerable distress in nurses and physicians. Our unit introduced multidisciplinary medical ethical decision making 5 years ago, which may partly explain the low MD at baseline. RELEVANCE TO CLINICAL PRACTICE: MD might be prevented by improved continuity of care, safe levels of staffing and better team communication, along with other targeted interventions with demonstrated effectiveness, such as palliative care programs and facilitated ethics conversations. PMID- 26380964 TI - How are your berries? Perspectives of Alaska's environmental managers on trends in wild berry abundance. AB - BACKGROUND: Wild berries are a valued traditional food in Alaska. Phytochemicals in wild berries may contribute to the prevention of vascular disease, cancer and cognitive decline, making berry consumption important to community health in rural areas. Little was known regarding which species of berries were important to Alaskan communities, the number of species typically picked in communities and whether recent environmental change has affected berry abundance or quality. OBJECTIVE: To identify species of wild berries that were consumed by people in different ecological regions of Alaska and to determine if perceived berry abundance was changing for some species or in some regions. DESIGN: We asked tribal environmental managers throughout Alaska for their views on which among 12 types of wild berries were important to their communities and whether berry harvests over the past decade were different than in previous years. We received responses from 96 individuals in 73 communities. RESULTS: Berries that were considered very important to communities differed among ecological regions of Alaska. Low-bush blueberry (Vaccinium uliginosum and V. caespitosum), cloudberry (Rubus chamaemorus) and salmonberry (Rubus spectabilis) were most frequently identified as very important berries for communities in the boreal, polar and maritime ecoregions, respectively. For 7 of the 12 berries on the survey, a majority of respondents indicated that in the past decade abundance had either declined or become more variable. CONCLUSIONS: Our study is an example of how environmental managers and participants in local observer networks can report on the status of wild resources in rural Alaska. Their observations suggest that there have been changes in the productivity of some wild berries in the past decade, resulting in greater uncertainty among communities regarding the security of berry harvests. Monitoring and experimental studies are needed to determine how environmental change may affect berry abundance. PMID- 26380965 TI - Preliteracy Speech Sound Production Skill and Linguistic Characteristics of Grade 3 Spellings: A Study Using the Templin Archive. AB - PURPOSE: This archival investigation examined the relationship between preliteracy speech sound production skill (SSPS) and spelling in Grade 3 using a dataset in which children's receptive vocabulary was generally within normal limits, speech therapy was not provided until Grade 2, and phonological awareness instruction was discouraged at the time data were collected. METHOD: Participants (N = 250), selected from the Templin Archive (Templin, 2004), varied on prekindergarten SSPS. Participants' real word spellings in Grade 3 were evaluated using a metric of linguistic knowledge, the Computerized Spelling Sensitivity System (Masterson & Apel, 2013). Relationships between kindergarten speech error types and later spellings also were explored. RESULTS: Prekindergarten children in the lowest SPSS (7th percentile) scored poorest among articulatory subgroups on both individual spelling elements (phonetic elements, junctures, and affixes) and acceptable spelling (using relatively more omissions and illegal spelling patterns). Within the 7th percentile subgroup, there were no statistical spelling differences between those with mostly atypical speech sound errors and those with mostly typical speech sound errors. CONCLUSIONS: Findings were consistent with predictions from dual route models of spelling that SSPS is one of many variables associated with spelling skill and that children with impaired SSPS are at risk for spelling difficulty. PMID- 26380966 TI - Cell-free protein synthesis of a cytotoxic cancer therapeutic: Onconase production and a just-add-water cell-free system. AB - Biotherapeutics have many promising applications, such as anti-cancer treatments, immune suppression, and vaccines. However, due to their biological nature, some biotherapeutics can be challenging to rapidly express and screen for activity through traditional recombinant methods. For example, difficult-to-express proteins may be cytotoxic or form inclusion bodies during expression, increasing the time, labor, and difficulty of purification and downstream characterization. One potential pathway to simplify the expression and screening of such therapeutics is to utilize cell-free protein synthesis. Cell-free systems offer a compelling alternative to in vivo production, due to their open and malleable reaction environments. In this work, we demonstrate the use of cell-free systems for the expression and direct screening of the difficult-to-express cytotoxic protein onconase. Using cell-free systems, onconase can be rapidly expressed in soluble, active form. Furthermore, the open nature of the reaction environment allows for direct and immediate downstream characterization without the need of purification. Also, we report the ability of a "just-add-water" lyophilized cell fee system to produce onconase. This lyophilized system remains viable after being stored above freezing for up to one year. The beneficial features of these cell-free systems make them compelling candidates for future biotherapeutic screening and production. PMID- 26380967 TI - A reliability assessment of a direct-observation park evaluation tool: the parks, activity and recreation among kids (PARK) tool. AB - BACKGROUND: Parks are increasingly being viewed as a resource that may influence youth obesity and physical activity (PA). Assessing park quality can be challenging as few tools assess park characteristics geared towards youth PA. Additionally, no studies have compared reliability estimates of items assessed in different countries, hindering aims towards generalizable park audit items. Finally, new satellite imaging technology is allowing for desktop identification of parks, however it remains unclear how this compares to direct observation park identification. The purpose of this study is 1) to describe the development and reliability of a youth-oriented direct-observation park audit tool tested in Montreal, Canada, and; 2) to compare reliability estimates of items with those drawn from a tool previously tested in Perth, Australia, with those same items tested in Montreal, Canada. METHODS: Items were drawn and adapted from two existing tools and 13 new items were newly developed for a total of 92 items. Parks were pre-identified using a GIS software and then verified and audited on site by observers. A total of 576 parks were evaluated. Cohen's kappa and percent agreement were used to assess the inter- and intra-rater reliability of each item. Inter-rater reliabilities of 17 items drawn from a tool previously tested in Australia were compared. RESULTS: Eighty-six percent of items had >= 75 % agreement and 83 % had kappa coefficients between 0.41 and 1. Among 40 test retest episodes kappa agreement was relatively high (>= 0.40) for all but four items. Percent agreement was excellent (>= 75 % agreement) for all but eight items. Inter-rater reliability estimates of the 17 items tested in Montreal and Perth were of similar magnitude. CONCLUSIONS: The tool is generally reliable and can be used to assess park characteristics that may be associated with youth PA. The items tested in Montreal and Perth are likely generalizable to other urban environments. PMID- 26380968 TI - The Oxford Shoulder Instability Score; validation in Dutch and first-time assessment of its smallest detectable change. AB - BACKGROUND: The Oxford Shoulder Instability Score (OSIS) is a short, self reported outcome measurement for patients with shoulder instability. In this study, the OSIS was validated in Dutch by testing the internal consistency, reliability, measurement error, validity and the floor and ceiling effects, and its smallest detectable change (SDC) was calculated. METHODS: A total of 138 patients were included. Internal consistency was calculated with Cronbach's alpha. Reliability (test-retest) was calculated with the intraclass correlation coefficient (ICC). The measurement error was calculated (SEM), and the SDC was estimated in a subgroup of 99 patients that completed the re-test after a mean of 13 days (5-30 days). Construct validity was evaluated by comparing the OSIS with the Western Ontario Shoulder Instability index (WOSI), the Simple Shoulder Test (SST), the Oxford Shoulder Score (OSS), the Disability of the Arm, Shoulder, and Hand assessment (DASH), and the Short Form-36 (SF-36). RESULTS: Internal consistency was good, with a Cronbach's alpha of 0.88. The reliability was excellent, with an ICC of 0.87. The SEM was 3.3 and the SDC was 9 points (on a scale of 0-48). Regarding the construct validity, 80% of the results were in accordance with the hypotheses, including a high correlation (0.82) with the WOSI. No floor or ceiling effects were found. CONCLUSIONS: The Dutch version of the OSIS showed good reliability and validity in a cohort of patients with shoulder instability. PMID- 26380970 TI - phoP, SPI1, SPI2 and aroA mutants of Salmonella Enteritidis induce a different immune response in chickens. AB - Poultry is the most frequent reservoir of non-typhoid Salmonella enterica for humans. Understanding the interactions between chickens and S. enterica is therefore important for vaccine design and subsequent decrease in the incidence of human salmonellosis. In this study we therefore characterized the interactions between chickens and phoP, aroA, SPI1 and SPI2 mutants of S. Enteritidis. First we tested the response of HD11 chicken macrophage-like cell line to S. Enteritidis infection monitoring the transcription of 36 genes related to immune response. All the mutants and the wild type strain induced inflammatory signaling in the HD11 cell line though the response to SPI1 mutant infection was different from the rest of the mutants. When newly hatched chickens were inoculated, the phoP as well as the SPI1 mutant did not induce an expression of any of the tested genes in the cecum. Despite this, such chickens were protected against challenge with wild-type S. Enteritidis. On the other hand, inoculation of chickens with the aroA or SPI2 mutant induced expression of 27 and 18 genes, respectively, including genes encoding immunoglobulins. Challenge of chickens inoculated with these two mutants resulted in repeated induction of 11 and 13 tested genes, respectively, including the genes encoding immunoglobulins. In conclusion, SPI1 and phoP mutants induced protective immunity without inducing an inflammatory response and antibody production. Inoculation of chickens with the SPI2 and aroA mutants also led to protective immunity but was associated with inflammation and antibody production. The differences in interaction between the mutants and chicken host can be used for a more detailed understanding of the chicken immune system. PMID- 26380969 TI - Challenges in the provision of healthcare services for migrants: a systematic review through providers' lens. AB - BACKGROUND: In recent years, cross-border migration has gained significant attention in high-level policy dialogues in numerous countries. While there exists some literature describing the health status of migrants, and exploring migrants' perceptions of service utilisation in receiving countries, there is still little evidence that examines the issue of health services for migrants through the lens of providers. This study therefore aims to systematically review the latest literature, which investigated perceptions and attitudes of healthcare providers in managing care for migrants, as well as examining the challenges and barriers faced in their practices. METHODS: A systematic review was performed by gathering evidence from three main online databases: Medline, Embase and Scopus, plus a purposive search from the World Health Organization's website and grey literature sources. The articles, published in English since 2000, were reviewed according to the following topics: (1) how healthcare providers interacted with individual migrant patients, (2) how workplace factors shaped services for migrants, and (3) how the external environment, specifically laws and professional norms influenced their practices. Key message of the articles were analysed by thematic analysis. RESULTS: Thirty seven articles were recruited for the final review. Key findings of the selected articles were synthesised and presented in the data extraction form. Quality of retrieved articles varied substantially. Almost all the selected articles had congruent findings regarding language andcultural challenges, and a lack of knowledge of a host country's health system amongst migrant patients. Most respondents expressed concerns over in-house constraints resulting from heavy workloads and the inadequacy of human resources. Professional norms strongly influenced the behaviours and attitudes of healthcare providers despite conflicting with laws that limited right to health services access for illegal migrants. DISCUSSION: The perceptions, attitudes and practices of practitioners in the provision of healthcare services for migrants were mainly influenced by: (1) diverse cultural beliefs and language differences, (2) limited institutional capacity, in terms of time and/or resource constraints, (3) the contradiction between professional ethics and laws that limited migrants' right to health care. Nevertheless, healthcare providers addressedsuch problems by partially ignoring the immigrants'precarious legal status, and using numerous tactics, including seeking help from civil society groups, to support their clinical practice. CONCLUSION: It was evident that healthcare providers faced several challenges in managing care for migrants, which included not only language and cultural barriers, but also resource constraints within their workplaces, and disharmony between the law and their professional norms. Further studies, which explore health care management for migrants in countries with different health insurance models, are recommended. PMID- 26380971 TI - Exploration of alternative splicing events in ten different grapevine cultivars. AB - BACKGROUND: The complex dynamics of gene regulation in plants are still far from being fully understood. Among many factors involved, alternative splicing (AS) in particular is one of the least well documented. For many years, AS has been considered of less relevant in plants, especially when compared to animals, however, since the introduction of next generation sequencing techniques the number of plant genes believed to be alternatively spliced has increased exponentially. RESULTS: Here, we performed a comprehensive high-throughput transcript sequencing of ten different grapevine cultivars, which resulted in the first high coverage atlas of the grape berry transcriptome. We also developed findAS, a software tool for the analysis of alternatively spliced junctions. We demonstrate that at least 44% of multi-exonic genes undergo AS and a large number of low abundance splice variants is present within the 131.622 splice junctions we have annotated from Pinot noir. CONCLUSIONS: Our analysis shows that ~70% of AS events have relatively low expression levels, furthermore alternative splice sites seem to be enriched near the constitutive ones in some extent showing the noise of the splicing mechanisms. However, AS seems to be extensively conserved among the 10 cultivars. PMID- 26380973 TI - Severe Methanol Poisoning with Supralethal Serum Formate Concentration: A Case Report. AB - OBJECTIVE: To present a case of survival without visual and central nervous system sequelae at a formate concentration of twice the reported lethal level. CLINICAL PRESENTATION AND INTERVENTION: This was a case of a 33-year-old man who ingested 1 liter of a toxic mixture of methanol and ethanol. Upon admission, he presented with anxiety, tachycardia and hypertension and had a serum formate level of 1,400 mg/l (normal range 0.9-2.1 mg/l), a methanol level of 806 mg/l (normal range 2-30 mg/l), an undetectable ethanol concentration and a normal lactate level. A 10% solution of ethanol and folinic acid was administered intravenously and two 8-hour sessions of intermittent hemodialysis were performed. The patient was discharged on the fifth day without sequelae of poisoning. The follow-up examinations 3 months and 2 years later revealed no damage to the basal ganglia. The patient had normal visual-evoked potential and findings on optical coherence tomography. The genetic analysis revealed a rare minor allele for the gene coding CYP2E1 enzyme of the microsomal ethanol oxidizing system. CONCLUSION: The patient survived acute methanol poisoning without long-term sequelae despite a high serum level of formic acid upon admission. PMID- 26380972 TI - Selenium Level and Dyslipidemia in Rural Elderly Chinese. AB - OBJECTIVE: Higher selenium level has been hypothesized to have the potential to reduce the risk of cardiovascular diseases including dyslipidemia. However, results from previous studies are inconsistent. This study aims to determine the association between selenium level and dyslipidemia in elderly Chinese with relatively low selenium status. METHODS: A cross-sectional study of 1859 participants aged 65 or older from four rural counties in China was conducted. Serum total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDLC) and low-density lipoprotein-cholesterol (LDLC), nail selenium concentration and APOE genotype were measured in all subjects. The four types of dyslipidemia were defined as >5.17 mmol/L for High-TC, >1.69 mmol/L for High-TG, >3.36 mmol/L for High-LDLC, and <1.04 mmol/L for Low-HDLC according to Chinese Guidelines on Prevention and Treatment of Dyslipidemia in Adults. Logistic models adjusting for age, gender, APOE genotype, body mass index, alcohol consumption, smoking, physical activity, medication use for cardiovascular diseases were used to examine the relationship between selenium levels and the risk of dyslipidemia. RESULTS: Mean nail selenium concentration was 0.465 MUg/gin this sample. Rates for High-TC, High-LDLC, High-TG, Low-HDLC were 18.13%, 13.23%, 12.21% and 32.76% respectively. Results from logistic models indicated that higher selenium levels were significantly associated with higher risk of High-TC, High-LDLC and lower risk of Low-HDLC adjusting for covariates (p < 0.0001). Compared with the lowest selenium quartile group, participants in selenium quartile groups 2, 3 and 4 had significantly higher rates of High-TC, High-LDLC, High-TG, and lower rate of Low HDLC adjusting for covariates. No significant association was observed between selenium level and the risk of High-TG. APOEepsilon4 carriers had higher rates of High-TC and High-LDLC. There was no interaction between selenium level and APOE with the rates of dyslipidemia. CONCLUSIONS: Our results suggest long-term selenium exposure level may be associated with the risk of dyslipidemia in elderly population. Future studies are needed to examine the underlying mechanism of the association. PMID- 26380974 TI - The association between maternal urinary phthalate concentrations and blood pressure in pregnancy: The HOME Study. AB - BACKGROUND: Exposure to phthalates, a class of endocrine disrupting chemicals, is ubiquitous. We examined the association of urinary phthalate metabolite concentrations during pregnancy with maternal blood pressure and risk of pregnancy-induced hypertensive diseases. METHODS: We used data from the Health Outcomes and Measures of the Environment Study, a prospective birth cohort of low risk pregnant women recruited between March 2003 and January 2006. We analyzed maternal urine samples collected at 16 and 26 weeks gestation for 9 phthalate monoester metabolites reflecting exposure to 6 phthalate diesters. Outcomes included maternal blood pressure at <20 and >= 20 weeks gestation and pregnancy induced hypertensive diseases (gestational hypertension, preeclampsia, eclampsia, and HELLP syndrome). RESULTS: Data were available for 369 women who gave birth to singleton, live-born infants without congenital anomalies. Of the phthalate metabolites evaluated, only mono-benzyl phthalate (MBzP) concentrations were significantly associated with maternal diastolic blood pressure at <20 weeks gestation. Women in the third MBzP tercile at 16 weeks gestation had diastolic blood pressure 2.2 (95% CI: 0.5-3.9) mm Hg higher at <20 weeks gestation and 2.8 (95% CI: 0.9-4.7) mm Hg higher at >= 20 weeks gestation compared to women in the first tercile. Compared to women in the first tercile, women in the top MBzP tercile at 16 weeks had an increased risk of developing pregnancy-induced hypertensive diseases (RR = 2.92, 95 % CI 1.15-7.41, p-value for trend = 0.01). MBzP concentrations at 26 weeks gestation were not as strongly associated with blood pressure at >= 20 weeks gestation or risk of pregnancy-induced hypertensive diseases. CONCLUSION: This study suggests that maternal urinary MBzP concentrations may be associated with increased diastolic blood pressure and risk of pregnancy-induced hypertensive diseases. PMID- 26380975 TI - Determination of the optimal mating age of colonised Glossina brevipalpis and Glossina austeni using walk-in field cages in South Africa. AB - BACKGROUND: For the control of Glossina brevipalpis and Glossina austeni that occur in South Africa an area-wide integrated pest management (AW-IPM) program with a sterile insect technique (SIT) component has been proposed. The quality of the released sterile male tsetse flies will greatly determine the success of the SIT component of the programme. Sterile males need to be able to compete with wild males immediately after their release in the affected area. The mating competitiveness can be affected by many factors including the optimal mating age of the fly which can have an impact on the timing of the release. METHODS: To assess the optimal mating age for G. brevipalpis and G. austeni, mating competitiveness studies were carried out in a walk-in field cage. First, the time of peak fly activity was determined by performing the experiment in the morning and then again in the afternoon. Thereafter, 3, 6 and 9-day-old male flies competed for 3-day-old virgin females. RESULTS: There were no significant differences in mating performance when the field cage experiments were done in the morning or in the afternoon. However, the mating latency was shorter in the afternoon than in the morning. For both species 9-day-old males mated significantly more often than 6 or 3-day-old males. Age did not affect the males' ability to transfer sperm, mating duration or the mating latency. All females that mated were inseminated. CONCLUSIONS: Age did influence the mating competitiveness of G. brevipalpis and G. austeni and it is recommended that sterile males are not released before the age of 9 days. Keeping the male flies in the rearing facility for 8 days will have economic and logistic consequences for AW-IPM programmes that have a SIT component. PMID- 26380976 TI - Combinatorial microRNAs suppress hypoxia-induced cardiomyocytes apoptosis. AB - BACKGROUND/AIMS: Our previous in silico analysis revealed potential synergy in the activities of micro(mi)RNAs in myocardial infarction. The present study investigated whether miR-1 and -21 act synergistically to protect against cardiomyocytes apoptosis. METHODS: Cell survival was analyzed with cell viability assay; apoptosis was detected by flow cytometry, terminal deoxynucleotidyl transferase dUTP nick end labeling, and the caspase-3 activity assay; and protein expression level was determined by western blotting. RESULTS: MiR-1:miR-21 and several other miRNA pairs were evaluated for their potentially synergistic effects against myocardial hypoxia in neonatal rat ventricular cardiomyocytes. Lower combination indices suggested that miRNA pairs acted synergistically to inhibit apoptosis; miR-1 and -21 jointly blocked hypoxia-induced cardiomyocytes apoptosis. Moreover, combined application of miR-1 and -21 activated Akt and blocked hypoxia-induced upregulation of p53 in these cells. CONCLUSION: MiR-1 and -21 exert synergistic effects against hypoxia-induced cardiomyocytes apoptosis. These results provide a basis for the development of combined miRNA-based therapeutics to treat cardiovascular diseases. PMID- 26380978 TI - Correction: Increased MU-Calpain Activity in Blasts of Common B-Precursor Childhood Acute Lymphoblastic Leukemia Correlates with Their Lower Susceptibility to Apoptosis. PMID- 26380977 TI - A Novel Detection Platform for Shrimp White Spot Syndrome Virus Using an ICP11 Dependent Immunomagnetic Reduction (IMR) Assay. AB - Shrimp white spot disease (WSD), which is caused by white spot syndrome virus (WSSV), is one of the world's most serious shrimp diseases. Our objective in this study was to use an immunomagnetic reduction (IMR) assay to develop a highly sensitive, automatic WSSV detection platform targeted against ICP11 (the most highly expressed WSSV protein). After characterizing the magnetic reagents (Fe3O4 magnetic nanoparticles coated with anti ICP11), the detection limit for ICP11 protein using IMR was approximately 2 x 10(-3) ng/ml, and the linear dynamic range of the assay was 0.1~1 x 10(6) ng/ml. In assays of ICP11 protein in pleopod protein lysates from healthy and WSSV-infected shrimp, IMR signals were successfully detected from shrimp with low WSSV genome copy numbers. We concluded that this IMR assay targeting ICP11 has potential for detecting the WSSV. PMID- 26380979 TI - Lysyl Hydroxylase 3 Localizes to Epidermal Basement Membrane and Is Reduced in Patients with Recessive Dystrophic Epidermolysis Bullosa. AB - Recessive dystrophic epidermolysis bullosa (RDEB) is caused by mutations in COL7A1 resulting in reduced or absent type VII collagen, aberrant anchoring fibril formation and subsequent dermal-epidermal fragility. Here, we identify a significant decrease in PLOD3 expression and its encoded protein, the collagen modifying enzyme lysyl hydroxylase 3 (LH3), in RDEB. We show abundant LH3 localising to the basement membrane in normal skin which is severely depleted in RDEB patient skin. We demonstrate expression is in-part regulated by endogenous type VII collagen and that, in agreement with previous studies, even small reductions in LH3 expression lead to significantly less secreted LH3 protein. Exogenous type VII collagen did not alter LH3 expression in cultured RDEB keratinocytes and we show that RDEB patients receiving bone marrow transplantation who demonstrate significant increase in type VII collagen do not show increased levels of LH3 at the basement membrane. Our data report a direct link between LH3 and endogenous type VII collagen expression concluding that reduction of LH3 at the basement membrane in patients with RDEB will likely have significant implications for disease progression and therapeutic intervention. PMID- 26380980 TI - Nurses' Practice Environment and Their Job Satisfaction: A Study on Nurses Caring for Older Adults in Shanghai. AB - AIM: To examine the job satisfaction of nurses who are caring for older adults in healthcare settings in Shanghai, and to explore the underlying factors in order to explain and predict nurses' job satisfaction. BACKGROUND: China has the largest elderly population in the world, and its population is aging rapidly. Studies on job satisfaction of nurses providing care for the elderly in China can help to identify problem areas and develop strategies for the improvement of nurses' working conditions. However, to date, this subject matter has not been thoroughly studied in the Chinese context. Previous studies in other countries show that many factors impact nurses' job satisfaction, with the practice environment being a critical factor. There is a serious nursing shortage in China, especially in the big cities such as Shanghai. Given the increasing care demand of the aging population, learning about the job satisfaction level among nurses who are caring for older adults can provide essential information to help attract and retain nurses in this specialty area. METHODS: A cross-sectional survey was conducted among 444 nurses in 22 elderly care institutions in Shanghai. The Chinese version of the Index of Work Satisfaction (IWS) and the Nursing Practice Environment Scale were instruments used. Inferential statistical tests used to analyze the data included Spearman correlation analysis, one-way analysis of variance, and hierarchical regression tests. RESULTS: The average overall IWS (part B) score was 135.21 +/- 19.34. Personality, job and organizational characteristics were found to be the most influential factors, and the practice environment was identified as having the strongest impact on job satisfaction (Beta = 0.494). CONCLUSION: Job satisfaction level among nurses who are caring for older adults in Shanghai is moderate, but the data suggest that this could be greatly increased if the nursing practice environment was improved. PMID- 26380981 TI - Exposure to ethanol during neurodevelopment modifies crucial offspring rat brain enzyme activities in a region-specific manner. AB - The experimental simulation of conditions falling within "the fetal alcohol spectrum disorder" (FASD) requires the maternal exposure to ethanol (EtOH) during crucial neurodevelopmental periods; EtOH has been linked to a number of neurotoxic effects on the fetus, which are dependent upon the extent and the magnitude of the maternal exposure to EtOH and for which very little is known with regard to the exact mechanism(s) involved. The current study has examined the effects of moderate maternal exposure to EtOH (10 % v/v in the drinking water) throughout gestation, or gestation and lactation, on crucial 21-day-old offspring Wistar rat brain parameters, such as the activities of acetylcholinesterase (AChE) and two adenosine triphosphatases (Na(+),K(+)-ATPase and Mg(2+)-ATPase), in major offspring CNS regions (frontal cortex, hippocampus, hypothalamus, cerebellum and pons). The implemented experimental setting has provided a comparative view of the neurotoxic effects of maternal exposure to EtOH between gestation alone and a wider exposure timeframe that better covers the human third trimester-matching CNS neurodevelopment period (gestation and lactation), and has revealed a CNS region-specific susceptibility of the examined crucial neurochemical parameters to the EtOH exposure schemes attempted. Amongst these parameters, of particular importance is the recorded extensive stimulation of Na(+),K(+)-ATPase in the frontal cortex of the EtOH-exposed offspring that seems to be a result of the deleterious effect of EtOH during gestation. Although this stimulation could be inversely related to the observed inhibition of AChE in the same CNS region, its dependency upon the EtOH-induced modulation of other systems of neurotransmission cannot be excluded and must be further clarified in future experimental attempts aiming to simulate and to shed more light on the milder forms of the FASD-related pathophysiology. PMID- 26380982 TI - The Prognostic Importance of Changes in Renal Function during Treatment for Acute Heart Failure Depends on Admission Renal Function. AB - BACKGROUND: Worsening and improving renal function during acute heart failure have been associated with adverse outcomes but few studies have considered the admission level of renal function upon which these changes are superimposed. OBJECTIVES: The objective of this study was to evaluate definitions that incorporate both admission renal function and change in renal function. METHODS: 696 patients with acute heart failure with calculable eGFR were classified by admission renal function (Reduced [R, eGFR<45 ml/min] or Preserved [P, eGFR>=45 ml/min]) and change over hospital admission (worsening [WRF]: eGFR >=20% decline; stable [SRF]; and improving [IRF]: eGFR >=20% increase). The primary outcome was all-cause mortality. The prevalence of Pres and Red renal function was 47.8% and 52.2%. The frequency of R-WRF, R-SRF, and R-IRF was 11.4%, 28.7%, and 12.1%, respectively; the incidence of P-WRF, P-SRF, and P-IRF was 5.7%, 35.3%, and 6.8%, respectively. Survival was shorter for patients with R-WRF compared to R-IRF (median survival times 13.9 months (95%CI 7.7-24.9) and 32.5 months (95%CI 18.8 56.1), respectively), resulting in an acceleration factor of 2.3 (p = 0.016). Thus, an increase compared with a decrease in renal function was associated with greater than two times longer survival among patients with Reduced renal function. PMID- 26380983 TI - Hypoxic Preconditioning Increases Survival and Pro-Angiogenic Capacity of Human Cord Blood Mesenchymal Stromal Cells In Vitro. AB - Hypoxic preconditioning was shown to improve the therapeutic efficacy of bone marrow-derived multipotent mesenchymal stromal cells (MSCs) upon transplantation in ischemic tissue. Given the interest in clinical applications of umbilical cord blood-derived MSCs, we developed a specific hypoxic preconditioning protocol and investigated its anti-apoptotic and pro-angiogenic effects on cord blood MSCs undergoing simulated ischemia in vitro by subjecting them to hypoxia and nutrient deprivation with or without preceding hypoxic preconditioning. Cell number, metabolic activity, surface marker expression, chromosomal stability, apoptosis (caspases-3/7 activity) and necrosis were determined, and phosphorylation, mRNA expression and protein secretion of selected apoptosis and angiogenesis regulating factors were quantified. Then, human umbilical vein endothelial cells (HUVEC) were subjected to simulated ischemia in co-culture with hypoxically preconditioned or naive cord blood MSCs, and HUVEC proliferation was measured. Migration, proliferation and nitric oxide production of HUVECs were determined in presence of cord blood MSC-conditioned medium. Cord blood MSCs proved least sensitive to simulated ischemia when they were preconditioned for 24 h, while their basic behavior, immunophenotype and karyotype in culture remained unchanged. Here, "post-ischemic" cell number and metabolic activity were enhanced and caspase-3/7 activity and lactate dehydrogenase release were reduced as compared to non-preconditioned cells. Phosphorylation of AKT and BAD, mRNA expression of BCL-XL, BAG1 and VEGF, and VEGF protein secretion were higher in preconditioned cells. Hypoxically preconditioned cord blood MSCs enhanced HUVEC proliferation and migration, while nitric oxide production remained unchanged. We conclude that hypoxic preconditioning protects cord blood MSCs by activation of anti-apoptotic signaling mechanisms and enhances their angiogenic potential. Hence, hypoxic preconditioning might be a translationally relevant strategy to increase the tolerance of cord blood MSCs to ischemia and improve their therapeutic efficacy in clinical applications. PMID- 26380984 TI - Soluble Urokinase Receptor Levels Are Correlated with Focal Segmental Glomerulosclerosis Lesions in IgA Nephropathy: A Cohort Study from China. AB - BACKGROUND: Soluble urokinase receptor (suPAR) may be involved in the pathological mechanisms of focal segmental glomerulosclerosis (FSGS) changes. However, it remains unclear whether suPAR is correlated with the FSGS-like lesions in IgA nephropathy (IgAN). METHODS: We measured the plasma suPAR levels in 138 patients with IgAN, and then their clinical and pathological relationships were analyzed. RESULTS: We found that the plasma suPAR levels were significantly correlated with age and renal function by both univariate and multivariate analysis in our IgAN patient cohort. Female had higher plasma suPAR levels and no significant correlation was observed between plasma suPAR levels and 24-h urine protein and highly sensitive C-reaction protein with multivariate analysis. In our cohort, sixty of these IgAN patients could be diagnosed with a type of FSGS lesions. The plasma suPAR levels were higher in the IgAN patients with FSGS lesions than in the IgAN patients without FSGS lesions by univariate (P < 0.0001) and multivariate (P < 0.001) analysis adjusting for other predictor variables, which might be helpful to differentiate the pathological changes with and without FSGS lesions. And the optimal cutoff value was 1806 pg/ml in this study. The plasma suPAR concentrations were also associated with the degree of tubular atrophy/interstitial fibrosis in both univariate and multivariate analysis. In multivariate analysis, the plasma suPAR levels were correlated with the percentage of crescents, not global sclerosis and arterial lesions. CONCLUSIONS: Our study suggested that the plasma suPAR levels were associated with age, gender, renal function, the degree of tubular atrophy/interstitial fibrosis and the percentage of crescent formation. The plasma suPAR might be a potential predictor for the presence of FSGS pathological lesions in Chinese patients with IgAN. PMID- 26380985 TI - Severity of the metabolic syndrome as a predictor of type 2 diabetes between childhood and adulthood: the Princeton Lipid Research Cohort Study. AB - AIMS/HYPOTHESIS: The aim of this study was to determine the long-term associations of a sex- and race/ethnicity-specific metabolic syndrome (MetS) severity z score from childhood and adulthood with a future diagnosis of type 2 diabetes mellitus. METHODS: We performed a prospective cohort study with evaluations from the Cincinnati Clinic of the National Heart Lung and Blood Institute Lipids Research Clinic (LRC) 1973-1976 and Princeton Follow-up Study (PFS) 1998-2003, and further disease status from the Princeton Health Update (PHU) 2010-2014. We assessed MetS severity as a predictor of incident type 2 diabetes among 629 cohort participants assessed at both the LRC and PFS and 354 participants at the PHU. RESULTS: Cohort participants had a mean age of 12.9 years at baseline (LRC), 38.4 years at the PFS and 49.6 years at the most recent follow-up. Childhood MetS z scores were associated with adult MetS z scores (p < 0.01). Compared with individuals who were disease-free at all time-points, those who developed type 2 diabetes by 1998-2003 and 2010-2014 had higher MetS severity z scores in childhood (p < 0.05). For every one-unit elevation in childhood MetS z score, the OR of developing future type 2 diabetes was 2.7 for incident disease by a mean age of 38.5 years (p < 0.01) and 2.8 for incident disease by a mean age of 49.6 years (p < 0.05). Regarding associations with the change in z score from childhood to adulthood, for every one-unit increase in MetS z score over time the OR of developing incident type 2 diabetes by a mean age of 49.6 years was 7.3 (p < 0.01). CONCLUSIONS/INTERPRETATION: The severity of MetS in childhood was associated with the incidence of adult type 2 diabetes and the degree of increase in this severity predicted future disease. These findings provide evidence of potential clinical utility in assessing MetS severity to detect risk and follow clinical progress over time. PMID- 26380987 TI - Matters arising from The BMJ's stance on assisted dying. PMID- 26380986 TI - Use of Targeted Exome Sequencing for Molecular Diagnosis of Skeletal Disorders. AB - Genetic disorders of the skeleton comprise a large group of more than 450 clinically distinct and genetically heterogeneous diseases associated with mutations in more than 300 genes. Achieving a definitive diagnosis is complicated due to the genetic heterogeneity of these disorders, their individual rarity and their diverse radiographic presentations. We used targeted exome sequencing and designed a 1.4 Mb panel for simultaneous testing of more than 4,800 exons in 309 genes involved in skeletal disorders. DNA from 69 individuals from 66 families with a known or suspected clinical diagnosis of a skeletal disorder was analyzed. Of 36 cases with a specific clinical hypothesis with a known genetic basis, mutations were identified for eight cases (22%). Of 20 cases with a suspected skeletal disorder but without a specific diagnosis, four causative mutations were identified. Also included were 11 cases with a specific skeletal disorder but for which there was at the time no known associated gene. For these cases, one mutation was identified in a known skeletal disease genes, and re-evaluation of the clinical phenotype in this case changed the diagnoses from osteodysplasia syndrome to Apert syndrome. These results suggest that the NGS panel provides a fast, accurate and cost-effective molecular diagnostic tool for identifying mutations in a highly genetically heterogeneous set of disorders such as genetic skeletal disorders. The data also stress the importance of a thorough clinical evaluation before DNA sequencing. The strategy should be applicable to other groups of disorders in which the molecular basis is largely known. PMID- 26380988 TI - The Acute Effect of Humic Acid on Iron Accumulation in Rats. AB - Free iron leads to the formation of pro-oxidant reactive oxygen species (ROS). Humic acids (HAs) enhance permeability of cellular wall and act as a chelator through electron transferring. This study was designed to test chelator effect of HA on iron as well as its anti-oxidant effect against the iron-induced hepatotoxicity and cardiotoxicity. The rats used were randomly divided into four groups (n = 8/group): group I (the control group); group II (the HA group), humic acid (562 mg/kg) was given over 10 days by oral gavage; group III (the iron group), iron III hydroxide polymaltose (250 mg/kg) was given over 10 days by intraperitoneal route; and group IV (the HA plus iron group), received the iron (similar to group II) plus humic acid (similar to those in groups II and III) group. Blood and two tissue samples both from liver and heart were obtained for biochemical and histopathological evaluations. Iron deposition, the iron-induced hepatotoxicity, and cardiotoxicity were demonstrated by histopathological and biochemical manner. However, no significant differences were observed in the serum biochemical values and the histopathological results among the iron and the HA plus iron groups in the liver tissue but not in the heart tissue. The protective effects of humic acid against iron-induced cardiotoxicity were shown but not against hepatotoxicity in our study. PMID- 26380989 TI - Ataxia-Telangiectasia Presenting as Cerebral Palsy and Recurrent Wheezing: A Case Report. AB - BACKGROUND: Ataxia-telangiectasia (A-T) is an autosomal recessive disease that consists of progressive cerebellar ataxia, variable immunodeficiency, sinopulmonary infections, oculocutaneous telangiectasia, radiosensitivity, early aging, and increased incidence of cancer. CASE REPORT: We report the case of an 8 year-old boy affected by A-T. At 12 months of age, he had a waddling gait, with his upper body leaning forward. Dystonic/dyskinetic cerebral palsy was diagnosed at the age of 3 years. At age 6 he was diagnosed with asthma based on recurrent wheezing episodes. A-T was confirmed at the age 8 years on the basis of clinical signs and laboratory findings (increased alpha fetoprotein--AFP, immunodeficiency, undetectable ataxia-telangiectasia mutated (ATM) protein on immunoblotting, and identification A-T mutation, 5932G>T). CONCLUSIONS: The clinical and immunological presentation of ataxia-telangiectasia (A-T) is very heterogeneous and diagnostically challenging, especially at an early age, leading to frequent misdiagnosis. PMID- 26380991 TI - Admission vitamin D status is associated with discharge destination in critically ill surgical patients. AB - BACKGROUND: Discharge destination after critical illness is increasingly recognized as a valuable patient-centered outcome. Recently, vitamin D status has been shown to be associated with important outcomes such as length of stay (LOS) and mortality in intensive care unit (ICU) patients. Our goal was to investigate whether vitamin D status on ICU admission is associated with discharge destination. METHODS: We performed a retrospective analysis from an ongoing prospective cohort study of vitamin D status in critical illness. Patients were recruited from two surgical ICUs at a single teaching hospital in Boston, Massachusetts. All patients had 25-hydroxyvitamin D (25OHD) levels measured within 24 h of ICU admission. Discharge destination was dichotomized as non-home or home. Locally weighted scatterplot smoothing (LOWESS) was used to graph the relationship between 25OHD levels and discharge destination. To investigate the association between 25OHD level and discharge destination, we performed logistic regression analyses, controlling for age, sex, race, body mass index, socioeconomic status, acute physiology and chronic health evaluation II score, need for emergent vs. non-emergent surgery, vitamin D supplementation status, and hospital LOS. RESULTS: 300 patients comprised the analytic cohort. Mean 25OHD level was 19 (standard deviation 8) ng/mL and 41 % of patients had a non-home discharge destination. LOWESS analysis demonstrated a near-inverse linear relationship between vitamin D status and non-home discharge destination to 25OHD levels around 10 ng/mL, with rapid flattening of the curve between levels of 10 and 20 ng/mL. Overall, 25OHD level at the outset of critical illness was inversely associated with non-home discharge destination (adjusted OR, 0.88; 95 % CI 0.82-0.95). When vitamin D status was dichotomized, patients with 25OHD levels <20 ng/mL had an almost 3-fold risk of a non-home discharge destination (adjusted OR, 2.74; 95 % CI 1.23-6.14) compared to patients with 25OHD levels >=20 ng/mL. CONCLUSIONS: Our results suggest that vitamin D status may be a modifiable risk factor for non-home discharge destination in surgical ICU patients. Future randomized, controlled trials are needed to determine whether vitamin D supplementation in surgical ICU patients can improve clinical outcomes such as the successful rate of discharge to home after critical illness. PMID- 26380990 TI - Breakthrough in cardiac arrest: reports from the 4th Paris International Conference. AB - Jean-Luc Diehl The French Intensive Care Society organized on 5th and 6th June 2014 its 4th "Paris International Conference in Intensive Care", whose principle is to bring together the best international experts on a hot topic in critical care medicine. The 2014 theme was "Breakthrough in cardiac arrest", with many high-quality updates on epidemiology, public health data, pre-hospital and in-ICU cares. The present review includes short summaries of the major presentations, classified into six main chapters: Epidemiology of CA Pre-hospital management Post-resuscitation management: targeted temperature management Post-resuscitation management: optimizing organ perfusion and metabolic parameters Neurological assessment of brain damages Public healthcare. PMID- 26380992 TI - Non-invasive monitoring of oxygen delivery in acutely ill patients: new frontiers. AB - Hypovolemia, anemia and hypoxemia may cause critical deterioration in the oxygen delivery (DO2). Their early detection followed by a prompt and appropriate intervention is a cornerstone in the care of critically ill patients. And yet, the remedies for these life-threatening conditions, namely fluids, blood and oxygen, have to be carefully titrated as they are all associated with severe side effects when administered in excess. New technological developments enable us to monitor the components of DO2 in a continuous non-invasive manner via the sensor of the traditional pulse oximeter. The ability to better assess oxygenation, hemoglobin levels and fluid responsiveness continuously and simultaneously may be of great help in managing the DO2. The non-invasive nature of this technology may also extend the benefits of advanced monitoring to wider patient populations. PMID- 26380993 TI - Right over left ventricular end-diastolic area relevance to predict hemodynamic intolerance of high-frequency oscillatory ventilation in patients with severe ARDS. AB - BACKGROUND: High-frequency oscillatory ventilation (HFOV) does not improve the prognosis of ARDS patients despite an improvement in oxygenation. This paradox may partly be explained by HFOV hemodynamic side-effects on right ventricular function. Our goal was to study the link between HFOV and hemodynamic effects and to test if the pre-HFOV right over left ventricular end-diastolic area (RVEDA/LVEDA) ratio, as a simple parameter of afterload-related RV dysfunction, could be used to predict HFOV hemodynamic intolerance in patients with severe ARDS. METHODS: Twenty-four patients were studied just before and within 3 h of HFOV using transthoracic echocardiography and transpulmonary thermodilution. RESULTS: Before HFOV, the mean PaO2/FiO2 ratio was 89 +/- 23. The number of patients with a RVEDA/LVEDA ratio >0.6 significantly increased after HFOV [11 (46 %) vs. 17 (71 %)]. Although HFOV did not significantly decrease the arterial pressure (systolic, diastolic, mean and pulse pressure), it significantly decreased the cardiac index (CI) by 13 +/- 18 % and significantly increased the RVEDA/LVEDA ratio by 14 +/- 11 %. A significant correlation was observed between pre-HFOV RVEDA/LVEDA ratio and CI diminution after HFOV (r = 0.78; p < 0.0001). A RVEDA/LVEDA ratio superior to 0.6 resulted in a CI decrease >15 % during HFOV with a sensitivity of 80 % (95 % confidence interval 44-98 %) and a specificity of 79 % (confidence interval 49-95 %). CONCLUSION: The RVEDA/LVEDA ratio measured just before HFOV predicts the hemodynamic intolerance of this technique in patients with severe ARDS. A high ratio under CMV raises questions about the use of HFOV in such patients. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01167621. PMID- 26380994 TI - Lowering bed occupancy: a life-saving intervention? PMID- 26380995 TI - Lowering levels of bed occupancy is associated with decreased inhospital mortality and improved performance on the 4-hour target in a UK District General Hospital. AB - OBJECTIVE: To evaluate whether there is an association between an intervention to reduce medical bed occupancy and performance on the 4-hour target and hospital mortality. METHODS: This before-and-after study was undertaken in a large UK District General Hospital over a 32 month period. A range of interventions were undertaken to reduce medical bed occupancy within the Trust. Performance on the 4 hour target and hospital mortality (hospital standardised mortality ratio (HSMR), summary hospital-level mortality indicator (SHMI) and crude mortality) were compared before, and after, intervention. Daily data on medical bed occupancy and percentage of patients meeting the 4-hour target was collected from hospital records. Segmented regression analysis of interrupted time-series method was used to estimate the changes in levels and trends in average medical bed occupancy, monthly performance on the target and monthly mortality measures (HSMR, SHMI and crude mortality) that followed the intervention. RESULTS: Mean medical bed occupancy decreased significantly from 93.7% to 90.2% (p=0.02). The trend change in target performance, when comparing preintervention and postintervention, revealed a significant improvement (p=0.019). The intervention was associated with a mean reduction in all markers of mortality (range 4.5-4.8%). SHMI (p=0.02) and crude mortality (p=0.018) showed significant trend changes after intervention. CONCLUSIONS: Lowering medical bed occupancy is associated with reduced patient mortality and improved ability of the acute Trust to achieve the 95% 4-hour target. Whole system transformation is required to create lower average medical bed occupancy. PMID- 26380996 TI - Factors Contributing to Speech Performance in Elderly Cochlear Implanted Patients: An FDG-PET Study: A Preliminary Study. AB - OBJECTIVE: The purpose was to evaluate brain plasticity that contributes to speech performance after cochlear implantation (CI) in postlingual elderly (>60 years) patients. MATERIALS AND METHODS: Fifteen elderly postlingual deaf patients who underwent preoperative brain fluorodeoxyglucose positron emission tomography (FDG-PET) and were followed-up for more than 1 year after CI were included. The mean age of these patients was 64.6 years (range, 60-80 years). Based on their sentence score at 1 year after CI surgery, the patients were classified into two groups: poor performers (CID score of <80) and good performers (CID score of >=80). The duration of deafness, age at operation, preoperative residual hearing, and preoperative brain metabolism were analyzed. SPM5 software was used for FDG PET image preprocessing and statistical analysis. RESULTS: Neither deafness duration nor preoperative residual hearing was associated with speech performance. The age at operation had little association with speech performance. Deaf patients whose brain metabolism was higher in frontotemporal regions became good CI users but those with higher metabolism in visual association areas became poor CI users. No significant cortical area of higher metabolism was associated with the duration of deafness. CONCLUSION: Overactivation in the visual processing pathway correlated with a poor CI outcome at 1 year. Deaf patients who are going to be poorer performers with CI devices maintain visual information processing during preoperative silent resting periods. PMID- 26380997 TI - Hearing Risk among Young Personal Listening Device Users: Effects at High Frequency and Extended High-Frequency Audiogram Thresholds. AB - OBJECTIVE: The usage of personal listening devices (PLDs) is associated with risks of hearing loss. The aim of this study is to evaluate the effects of music exposure from these devices on high-frequency hearing thresholds of PLD users. MATERIALS AND METHODS: A total of 282 young adults were questioned regarding their listening habits and symptoms associated with PLD listening. Their audiogram thresholds were determined at high (3-8 kHz) frequencies and extended high frequencies (EHFs, 9-16 kHz). The preferred listening volumes of PLD users were used to compute their overall 8-h equivalent music exposure levels (LAeq8h). RESULTS: Approximately 80% of the subjects were regular PLD users. Of these, 20.1% had LAeq8h of >=75 dBA, while 4.4% of them had LAeq8h of >=85 dBA, which carries a high risk of hearing damage. Compared with those exposed to LAeq8h of <75 dBA, subjects who had LAeq8h of >=75 dBA reported a significantly higher incidence of tinnitus and difficulty in hearing others immediately after using PLDs. PLD users who were exposed to LAeq8h of >=75 dBA and had been using their devices for >=4 years also showed significantly higher mean audiogram thresholds compared with non-users at most EHFs tested. In addition, the thresholds of PLD users at EHFs showed a weak but significant positive correlation with their LAeq8h. CONCLUSION: The present findings suggest that excessive exposure to music among PLD users may lead to initial effects on their hearing at very high frequencies. PMID- 26380999 TI - Binaural Interaction Component in Speech Evoked Auditory Brainstem Responses. AB - OBJECTIVE: This article aims to describe the characteristics of the binaural interaction component (BIC) of speech-evoked auditory brainstem response (ABR). MATERIALS AND METHODS: All 15 subjects had normal peripheral hearing sensitivity. ABRs were elicited by speech stimulus /da/. RESULTS: The first BIC (BIC-SP1) in the speech-evoked ABR occurred at around 6 ms in the region of peak V. The second BIC (BIC-SP2) was present around 8 ms in the latency region of peak A. The third and fourth BICs of speech-evoked ABR (BIC-SP3 & BIC-SP4) were observed at around 36 ms and 46 ms, respectively, in the latency regions of peaks E and F, respectively. BIC-SP1 and BIC-SP2 were present in all subjects tested (100%), whereas BIC-SP3 and BIC-SP4 were present in 11 (73%). CONCLUSION: Because ABRs are not affected by sleep and mature early, this tool can be evaluated in identifying binaural interaction in younger and difficult-to-test populations. PMID- 26380998 TI - Recent Rehabilitation Experience with Pediatric ABI Users. AB - OBJECTIVE: The aim of this study is to describe the rehabilitative outcomes of pediatric auditory brainstem implant (ABI) users in the Department of Otolaryngology in the Hacettepe University. It was a retrospective study, and all patients' files were reviewed. MATERIALS AND METHODS: The data was collected from 41 children who were fitted with ABI between 2005 and 2013. Inclusion criteria for children in our study are profound, congenital bilateral sensory-neural hearing loss with anomalies (such as cochlear, labyrinthine, and cochlear nerve aplasia) and more than one year of auditory experience with ABI. Post-meningitis patients and neurofibromatosis type 2 (NF2) patients were excluded. Auditory perception was evaluated using the Meaningful Auditory Integration Scale (MAIS), Functioning after Pediatric Cochlear Implantation (FAPCI) instrument, Categories of Auditory Performance (CAP), and Children's Auditory Perception Skills Test in Turkish (CIAT). Speech intelligibility was categorized with speech intelligibility rating (SIR), and language development was assessed using the Test of Early Language Development-Third Edition (TELD-3) and Manchester Spoken Language Development Scale (MSLD). RESULTS: All patients gained basic audiological functions and were able to recognize and discriminate sounds by the third month of ABI surgery. According to the duration of ABI use and learning skills, patients revealed development from word identification to sentence recognition level in a wide spectrum. CONCLUSION: Preliminary results indicate that all children have gained basic auditory perception skills. On the other hand, language and speech development data were varying among children. Additional handicaps seemed to slow down progression. Secondary improvement was seen at psychosocial areas with respect to behavioral and social adjustment as well as eagerness to start communication. PMID- 26381000 TI - The Prevalence of Gap Junction Protein Beta 2 (GJB2) Mutations in Non Syndromic Sensorineural Hearing Loss in Cukurova Region. AB - OBJECTIVE: To date, studies in all populations showed that mutations in the gene of Gap junction protein beta 2 (GJB2) play an important role in non-syndromic autosomal recessive congenital hearing loss. The aim of this study was to evaluate GJB2 gene of patients with hearing loss in our region using deoxyribonucleic acid (DNA) sequencing method and to demonstrate region-specific mutation and polymorphism distribution. MATERIALS AND METHODS: Patients who had bilateral severe sensorineural non-syndromic hearing loss identified by audiologic evaluation were included. Peripheral blood samples were collected and the GJB2 gene exon1 and exon 2 regions were amplified by polymerase chain reaction (PCR). Obtained PCR products were sequenced by the DNA sequence analysis method (SeqFinder Sequencing System; ABI 3130; Foster City, CA, USA) and analyzed using the SeqScape software. RESULTS: Of the 77 patients, 16 had homozygous or heterozygous mutation. CONCLUSION: The mutation of 35delG, which is known as the most frequent mutation of GJB2 gene, was also the most frequently seen mutation at a ratio of 5.5% in patients with hearing loss in our region; this was followed by the V27I mutation. As this is the first study conducted by sequence analysis in our region, it was worth to be presented in terms of showing the distribution of mutation. PMID- 26381001 TI - Recovery of Idiopathic Sudden Sensorineural Hearing Loss. AB - OBJECTIVE: The objective was to identify and evaluate factors that may influence the recovery rate in patients with idiopathic sudden sensorineural hearing loss (ISSNHL). MATERIALS AND METHODS: A retrospective analysis was performed for patients with sudden sensorineural hearing loss between 2009 and 2013. Those with an identified etiology were excluded. The patients were divided into four treatment groups: (i) systemic corticosteroids (SC) only, (ii) SC+low-molecular weight heparin (LMWH), (iii) SC+hyperbaric oxygen (HBO), and (iv) SC+LMWH+HBO. Recovery was evaluated according to Siegel's criteria. Age, initial hearing level, onset, treatment and audiogram types, comorbidities, and associated tinnitus and vestibular symptoms were investigated for their impact on prognosis. RESULTS: Two hundred five patients with ISSNHL were included. Recovery was seen in 59% of the patients. The complete recovery rate was significantly lower in patients older than 60 years and in patients presenting with profound hearing loss. Different audiogram curves had no significant effect on recovery. Sudden hearing loss was accompanied by tinnitus in 107 (52.1%) patients and vestibular symptoms in 55 (26.8%); however, neither was noted to affect prognosis. Different treatment combinations did not significantly affect prognosis. However, hypertension and a delay in treatment by more than 10 days from the onset of hearing loss were associated with a worse prognosis. CONCLUSION: Profound hearing loss, older than 60 years, a delay in treatment by more than 10 days, and hypertension were negative prognostic factors in this study, whereas, the type of audiogram curve and addition of HBO to SC did not affect prognosis. PMID- 26381002 TI - Analysis of Vestibular Evoked Myogenic Potentials and Electrocochleography in Noise Induced Hearing Loss. AB - OBJECTIVE: Our objective was to analyze the electrocochleography (ECoG) and cervical vestibular evoked myogenic potential (cVEMP) results of patients with noise-induced hearing loss (NIHL). MATERIALS AND METHODS: The study included 20 patients with NIHL. Pure-tone audiometry, tympanic membrane ECoG, and cVEMP were performed on all patients. The patients were divided into two groups based on averaged thresholds at 4, 6, and 8 kHz; whereby, group 1 comprised patients who had a threshold higher than 68.3 dB HL, whereas group 2 comprised patients with a threshold lower than 68.3 dB HL. RESULTS: Group 2 had a significantly higher number of patients with abnormal cVEMP values (63% versus 28%) (p=0.028). There was no significant difference in the incidence of ECoG abnormality between the groups (p>0.05), but there was a significant difference in the incidence of recognizable ECoG potentials between the groups (p<0.05). When only patients with vertigo/dizziness were considered, the group with vertigo and a lower degree of hearing loss (group 2) showed a higher incidence of abnormal cVEMP (p<0.05). CONCLUSION: Although the anatomical proximity of the sacculus to the cochlea leads to the consideration of a common involvement of these structures in NIHL, our results did not support the idea of a common and proportional involvement of the vestibular and auditory systems. Our study shows that saccular involvement is disproportionate to auditory involvement in NIHL. PMID- 26381003 TI - Normal Gain of VOR with Refixation Saccades in Patients with Unilateral Vestibulopathy. AB - OBJECTIVE: To characterize the response in the video head-impulse test for the assessment of the vestibulo-ocular reflex (VOR) in patients because of vertigo and dizziness. MATERIALS AND METHODS: After rightward and leftward head impulses, the following results evaluated were: gain of the reflex and appearance of refixation saccades. A particular type of response (normal gain VOR and refixation saccades) was evaluated in a group of patients. RESULTS: In patients with a unilateral abnormality consisting of normal gain and refixation saccades, there was a close concordance with the diseased side and the side to which head impulses elicited the abnormal result. CONCLUSION: In the assessment of patients with dizziness, finding a normal gain VOR with refixation saccades indicates the existence of a peripheral vestibulopathy and localizes to the side of the lesion. PMID- 26381004 TI - Histamine Antagonists for Treatment of Peripheral Vertigo: A Meta-Analysis. AB - OBJECTIVE: Vertigo, the hallucination of movement of oneself or one's surroundings, can have substantial adverse effects on the quality of life of affected patients. It is essential to decrease the frequency, severity, and duration of vertigo attacks using effective medications with minimal debilitating adverse effects. We performed a meta-analysis of available clinical trials to evaluate the efficacy of histamine antagonists in the treatment of vertigo compared to the rate of resolution in untreated control groups. MATERIALS AND METHODS: A systematic search of articles in any language from January 1970 to March 2015 was performed through the following databases: the Cochrane Central Register of Controlled Trials, Medical Literature Analysis and Retrieval System Online, the Excerpta Medica Database, Cumulative Index to Nursing and Allied Health Literature, Latin American and Caribbean Health Sciences Literature, Allied and Complementary Medicine Database, Web of Science, ClinicalTrials.gov, and Google. Randomized controlled trials comparing each kind of antihistamine to untreated control participants in the treatment of vertigo (blinded/unblinded) were screened for inclusion. Three reviewers separately performed data extraction from the included trials using a standard data abstraction form. Three other researchers read the final list of all articles retained. Discrepancies were settled by mutual consensus between the authors. Random effects models were applied to estimate the pooled odds ratio (OR) and 95% confidence interval (CI) using the Review Manager software. The evaluation of publication bias was performed by Egger's test and Begg's funnel plot. RESULTS: We identified 13 eligible citations. The pooled OR was 5.370, 95% CI (3.263-8.839), and I2=56.0%, with no obvious evidence of publication bias. CONCLUSION: Our results provide clarification of the effectiveness of several categories of histamine antagonists compared with placebos in controlling peripheral vertigo. PMID- 26381005 TI - Ossicular Chain Lesions in Tympanic Perforations and Chronic Otitis Media without Cholesteatoma. AB - OBJECTIVE: The first aim was to determine the prevalence, kind, and functional effects on hearing of ossicular chain suffering (OCS) in chronic otitis without cholesteatoma (NCOM) and tympanic perforations (TP). The second aim was to correlate the findings with clinical parameters and hearing level. MATERIALS AND METHODS: The study group comprised 250 consecutive patients affected by NCOM and who were subjected to tympanoplasty and never operated on before. Each patient underwent preoperative pure tone audiometry. Ossicles were evaluated during surgery. The incidence of OCS in NCOM was reported in 15-62% of the patients. RESULTS: Ossicular chain suffering was found in 26 out of the 250 patients included in the overall sample (10%). It was found in 7% of the patients affected by TP without otorrhea and in 19% of the patients affected by chronic ear discharge with drum perforation. OCS was found most frequently in posterior eardrum perforations and in patients with bilateral disease. The incus was the ossicle most frequently interested by resorption (92% of the patients). The air conduction threshold and air bone gap were more impaired in NCOM than in TP. CONCLUSION: Ossicular chain damages in patients with non-cholesteatomatous middle ear pathologies are not frequent and are present in no more than 10% of the patients, but lesions found were similar to those reported in patients with cholesteatoma. Otorrhea, posterior perforation, and bilateral disease can be considered as good predictors of OCS. PMID- 26381006 TI - Management of Acquired Atresia of the External Auditory Canal. AB - OBJECTIVE: The aim was to evaluate surgical techniques and their relationship to postoperative success rate and hearing outcomes in acquired atresia of the external auditory canal. MATERIALS AND METHODS: In this article, 24 patients with acquired atresia of the external auditory canal were retrospectively evaluated regarding their canal status, hearing, and postoperative success. RESULTS: Acquired stenosis occurs more commonly in males with a male: female ratio of 2 3:1; it seems to be a disorder affecting young adults. Previous ear surgery (13 patients, 54.2%) and external ear trauma (11 patients, 45.8%) were the main etiological factors of acquired ear canal stenosis. Mastoidectomy (12/13) and traffic accidents (8/11) comprise the majority of these etiological factors. Endaural incision is performed in 79.2% and postauricular incision for 20.8% of cases during the operation. As types of surgical approach, transcanal (70.8%), transmastoid (20.8%), and combined (8.4%) approaches are chosen. The atretic plate is generally located at the bony-cartilaginous junction (37.5%) and in the cartilaginous canal (33.3%); the bony canal is involved in a few cases only. Preserved healthy canal skin, split- or full-thickness skin grafts, or pre- or postauricular skin flaps are used to line the ear canal, but preserved healthy canal skin is preferred. CONCLUSION: The results of surgery are generally satisfactory, and complications are few if surgical principles are followed. PMID- 26381007 TI - Change in Detection Rate of Methicillin-Resistant Staphylococcus aureus and Pseudomonas aeruginosa and Their Antibiotic Sensitivities in Patients with Chronic Suppurative Otitis Media. AB - OBJECTIVE: To investigate changes in Pseudomonas aeruginosa (PA) and methicillin resistant Staphylococcus aureus (MRSA) and their antibiotic sensitivities over 13 years in patients diagnosed with chronic suppurative otitis media (CSOM). MATERIALS AND METHODS: The current study reports on a retrospective analysis of the outcomes of 2256 outpatients who visited the Department of Otorhinolaryngology clinics of 3 tertiary medical centers and who were diagnosed with chronic otitis media (COM) or chronic cholesteatomatous otitis media (CCOM) from January 2001 to December 2013. Aural discharge was collected from each patient. Infectious bacteria were identified, and their antibiotic sensitivities were determined. RESULTS: The most frequent age range of patients diagnosed with CSOM was 41 to 50 years. In patients aged more than 30 years, CSOM was more frequent in females than in males, whereas in those aged less than 30 years, it was more frequent in males. Regardless of age, the isolated MRSA strains showed high sensitivity to vancomycin, teicoplanin, and trimethoprim/sulfamethoxazole, whereas the isolated PA strains showed high sensitivity to cefepime, amikacin, and ceftazidime. The isolation rate of MRSA in patients with CSOM slightly decreased over the 13-year study period; however, PA resistance to quinolones and aminoglycosides showed a tendency to increase. CONCLUSION: Bacteria isolated from patients with CSOM showed little change between 2001 and 2013, whereas their antibiotic resistance showed changes; in particular, increased PA resistance to quinolones was observed. Empirical antibiotic treatment can lead to bacterial resistance, and changes in antimicrobial agents commonly used to treat CSOM should be considered. PMID- 26381008 TI - Wideband Tympanometry Normative Data for Turkish Young Adult Population. AB - OBJECTIVE: The aim of this study was to obtain norm values for a young adult Turkish group and to investigate the differences between female and male subjects in terms of wideband tympanometry. MATERIALS AND METHODS: One hundred ten young adult volunteers (mean+/-SD: 21.1+/-1.9 years) participated in this study. The measurements of wideband tympanometry were performed at octave frequencies between 226 Hz and 8000 Hz using Titan version 3.1. The stimulus level was set at 100 dB peSPL. RESULTS: A cross-sectional study design was used. In total, 218 ears were tested. A significant relationship was found between gender and absorbance values for the frequency band from 3100 Hz to 6900 Hz. The difference between the middle ear resonance frequency and ear canal volume (ECV) of the male and female subjects was also found to be significant. The difference in ECV may result from the difference in body size between the male and female subjects because there was a significant relationship among ECV and the height and weight. CONCLUSION: According to these results, it can be concluded that using separate norms for males and females may increase test specificity and sensitivity for the diagnosis of disorders, such as ossicular discontinuity and tympanic membrane perforations, affecting the high-frequency region. PMID- 26381009 TI - Bonebridge Implantation for Conductive Hearing Loss in a Patient with Oval Window Atresia. AB - The occurrence of oval window atresia is a rare anomaly with conductive hearing loss. Traditional atresia surgeries involve challenging surgical techniques with risks of irreversible inner ear damage. Recent reports on Bonebridge (Medel, Innsbruck, Austria), a novel implantable bone conduction hearing aid system, assert that the device is safe and effective for conductive hearing loss. We present a case of Bonebridge implantation in an eight-year-old girl with bilateral oval window atresia. PMID- 26381010 TI - A Rare Cause of Hearing Loss: Susac Syndrome. AB - Susac's syndrome is a rare autoimmune disease, which is characterized by microangiopathic changes that affects the brain, retina, and cochlea. It is mainly characterized by asymptomatic cerebral infarctions, low-and mid-frequency sensorineural hearing loss, and bilateral distal retinal artery occlusions. Otolaryngologists should be familiar with Susac's syndrome because hearing loss may be the initial presenting symptom. The recommended treatment options vary from antithrombotic to immunomodulatory drugs. Although in its early stage, remission from the disease or self-limiting clinical course may be observed. Residual disabilities such as blindness, deafness, and dementia may also be presented in its late stages. Awareness of the condition and suspicion in selected patients will provide early diagnosis and treatment, which are both important to prevent the development of severe sequelae. PMID- 26381011 TI - A Rare Case of Hearing Impairment due to Cerebello-Pontine Angle Lesion: Trigeminal Schwannoma. AB - Schwannoma of the trigeminal nerve is a rare condition. Even rarer is hearing loss occurring as a result of this lesion. The aim of this study is to highlight this rare cause of hearing impairment. Here we report the clinical features and findings of the imaging and audiological investigations of a case of trigeminal schwannoma diagnosed at our institution. Our patient presented with headache, giddiness, tinnitus, left-sided facial weakness, left-sided hearing loss, right sided hemiplegia, and unintelligible speech. Radiological studies revealed a large well-defined mass lesion in the left cerebellopontine angle with a significant mass effect on posterior fossa structures, suggestive of trigeminal nerve tumor. Audio-vestibular assessment was done with pure tone audiometry, impedance audiometry, otoacoustic emission, brainstem-evoked response audiometry, and electronystagmography, which pointed toward a retrocochlear pathology for hearing loss and imbalance. PMID- 26381012 TI - Osteopetrosis of the Temporal Bone Treated with Cochlear Implant. AB - Osteopetrosis is a heterogeneous group of skeletal disorders. It is a rare genetic disease caused by osteoclast dysfunction, leading to invalid bone desorption and remodeling and an increase in skeletal mass and density. We present the case of a 52-year-old female with osteopetrosis of the temporal bone. She reported loss of hearing in her left ear 14 years ago because of a head trauma. Four months ago, she was conservatively treated because of sudden sensorineural hearing loss in her right ear with no improvement. Her pure tone average audiogram was bilaterally 90 dB with 10% speech recognition. The patient was implanted with a cochlear implant. Except for the extremely thick and dense cortical bone of the mastoid, surgery was uneventful. Speech recognition 6 months after the surgery showed 75%. The results were stable for 3 years follow-up. Patients with profound hearing loss caused by osteopetrosis may benefit from cochlear implantation. PMID- 26381013 TI - Audiovestibular Manifestations in Patients with Ankylosing Spondylitis--A Case Report and Review of the Literature. AB - Ankylosing spondylitis is a chronic systemic inflammatory disease of unknown origin affecting up to 1% of the population. Audiovestibular impairment has been observed in ankylosing spondylitis and sensorineural hearing loss (SNHL) is the most common form. The cause of SNHL is still unknown but the possible causes are as follows: vascular inflammation (obliterative vasculitis) of small vessels, ossification of the articular tissue of the middle ear, and use of non-steroid anti-inflammatory drugs. This is a case report of a patient with ankylosing spondylitis and SNHL along with a discussion of the literature regarding cochleovestibular impairment in ankylosing spondylitis. PMID- 26381014 TI - Ruthenium Catalyzed Selective Hydroboration of Carbonyl Compounds. AB - Using the [Ru(p-cymene)Cl2]2 (1) complex, catalytic hydroboration of aldehydes and ketones with pinacolborane under neat and mild conditions is reported. At rt, chemoselective hydroboration of aldehydes over the ketones is also attained. Mechanistic studies confirmed the immediate formation of monohydride bridged dinuclear complex [{(eta(6)-p-cymene)RuCl}2(MU-H-MU-Cl)] (1b) from the reaction of 1 with pinacolborane, which catalyzed the highly efficient hydroboration reactions. The catalytic cycle containing mononuclear Ru-H species and intramolecular 1,3-hydride transfer is postulated. PMID- 26381015 TI - Vascular, but not luminal, activation of FFAR1 (GPR40) stimulates GLP-1 secretion from isolated perfused rat small intestine. AB - Glucagon-like peptide 1 (GLP-1) plays a central role in modern treatment of type 2 diabetes (T2DM) in the form of GLP-1 enhancers and GLP-1 mimetics. An alternative treatment strategy is to stimulate endogenous GLP-1 secretion from enteroendocrine L cells using a targeted approach. The G-protein-coupled receptor, FFAR1 (previously GPR40), expressed on L cells and activated by long chain fatty acids (LCFAs) is a potential target. A link between FFAR1 activation and GLP-1 secretion has been demonstrated in cellular models and small-molecule FFAR1 agonists have been developed. In this study, we examined the effect of FFAR1 activation on GLP-1 secretion using isolated, perfused small intestines from rats, a physiologically relevant model allowing distinction between direct and indirect effects of FFAR1 activation. The endogenous FFAR1 ligand, linoleic acid (LA), and four synthetic FFAR1 agonists (TAK-875, AMG 837, AM-1638, and AM 5262) were administered through intraluminal and intra-arterial routes, respectively, and dynamic changes in GLP-1 secretion were evaluated. Vascular administration of 10 MUmol/L TAK-875, 10 MUmol/L AMG 837, 1 MUmol/L and 0.1 MUmol/L AM-1638, 1 MUmol/L AM-6252, and 1 mmol/L LA, all significantly increased GLP-1 secretion compared to basal levels (P < 0.05), whereas luminal administration of LA and FFAR1 agonists was ineffective. Thus, both natural and small-molecule agonists of the FFAR1 receptor appear to require absorption prior to stimulating GLP-1 secretion, indicating that therapies based on activation of nutrient sensing may be more complex than hitherto expected. PMID- 26381016 TI - Transmembrane proteoglycans syndecan-2, 4, receptor candidates for the impact of HGF and FGF2 on semaphorin 3A expression in early-differentiated myoblasts. AB - Regenerative mechanisms that regulate intramuscular motor innervation are thought to reside in the spatiotemporal expression of axon-guidance molecules. Our previous studies proposed an unexplored role of resident myogenic stem cell (satellite cell)-derived myoblasts as a key presenter of a secreted neural chemorepellent semaphorin 3A (Sema3A); hepatocyte growth factor (HGF) and basic fibroblast growth factor (FGF2) triggered its expression exclusively at the early differentiation phase. In order to advance this concept, the present study described that transmembrane heparan/chondroitin sulfate proteoglycans syndecan 2, 4 may be the plausible receptor candidates for HGF and FGF2 to signal Sema3A expression. Results showed that mRNA expression of syndecan-2, 4 was abundant (two magnitudes higher than syndecan-1, 3) in early-differentiated myoblasts and their in vitro knockdown diminished the HGF/FGF2-induced expression of Sema3A down to a baseline level. Pretreatment with heparitinase and chondroitinase ABC decreased the HGF and FGF2 responses, respectively, in non-knockdown cultures, supporting a possible model that HGF and FGF2 may bind to heparan and chondroitin sulfate chains of syndecan-2, 4 to signal Sema3A expression. The findings, therefore, extend our understanding that HGF/FGF2-syndecan-2, 4 association may stimulate a burst of Sema3A secretion by myoblasts recruited to the site of muscle injury; this would ensure a coordinated delay in the attachment of motoneuron terminals onto fibers early in muscle regeneration, and thus synchronize the recovery of muscle fiber integrity and the early resolution of inflammation after injury with reinnervation toward functional recovery. PMID- 26381017 TI - Effects of leptin on sympathetic nerve activity in conscious mice. AB - The adipocyte-derived hormone, leptin, has emerged as an important regulator of regional sympathetic nerve activity (SNA) with pathophysiological implications in obesity. Genetically engineered mice are useful to understand the molecular pathways underlying the SNA responses evoked by leptin. However, so far the effect of leptin on direct SNA in mice has been studied under general anesthesia. Here, we examined the sympathetic responses evoked by leptin in conscious mice. Mice were instrumented, under ketamine/xylazine anesthesia, with renal or lumbar SNA recordings using a thin (40 gauge) bipolar platinum-iridium wire. The electrodes were exteriorized at the nape of the neck and mice were allowed (5 h) to recover from anesthesia. Interestingly, the reflex increases in renal and lumbar SNA caused by sodium nitroprusside (SNP)-induced hypotension was higher in the conscious phase versus the anesthetized state, whereas the increase in both renal and lumbar SNA evoked by leptin did not differ between anesthetized or conscious mice. Next, we assessed whether isoflurane anesthesia would yield a better outcome. Again, the SNP-induced increase in renal SNA and baroreceptor renal SNA reflex were significantly elevated in the conscious states relative to isoflurane-anesthetized phase, but the renal SNA response induced by leptin in the conscious states were qualitatively comparable to those evoked above. Thus, despite improvement in sympathetic reflexes in conscious mice the sympathetic responses evoked by leptin mimic those induced during anesthesia. PMID- 26381018 TI - Grain Size and Interface Dependence of Bias Stress Stability of n-Type Organic Field Effect Transistors. AB - The effect of grain size and interface dependence of bias stress stability of C60 based n-type organic field effect transistors (OFETs) has been studied. It has been realized that, with increasing grain size of C60, the bias stress induced threshold voltage shift can be controlled and this effect is mainly attributed to the mechanism of charge trapping at grain boundaries. It is further studied that the growth of C60 on the surface of parylene at elevated substrate temperature leads to the creation of radicals at the interface between the active layer and the gate dielectric. These radicals help to improve the bias stress stability of C60-based n-type OFETs. For achieving the bias stress stability, we have presented a procedure of creation of radicals at the interface between C60 and parylene in single gate OFETs instead of dual gate OFETs. PMID- 26381019 TI - Effects-Directed Analysis of Dissolved Organic Compounds in Oil Sands Process Affected Water. AB - Acute toxicity of oil sands process-affected water (OSPW) is caused by its complex mixture of bitumen-derived organics, but the specific chemical classes that are most toxic have not been demonstrated. Here, effects-directed analysis was used to determine the most acutely toxic chemical classes in OSPW collected from the world's first oil sands end-pit lake. Three sequential rounds of fractionation, chemical analysis (ultrahigh resolution mass spectrometry), and acute toxicity testing (96 h fathead minnow embryo lethality and 15 min Microtox bioassay) were conducted. Following primary fractionation, toxicity was primarily attributable to the neutral extractable fraction (F1-NE), containing 27% of original organics mass. In secondary fractionation, F1-NE was subfractionated by alkaline water washing, and toxicity was primarily isolated to the ionizable fraction (F2-NE2), containing 18.5% of the original organic mass. In the final round, chromatographic subfractionation of F2-NE2 resulted in two toxic fractions, with the most potent (F3-NE2a, 11% of original organic mass) containing predominantly naphthenic acids (O2(-)). The less-toxic fraction (F3 NE2b, 8% of original organic mass) contained predominantly nonacid species (O(+), O2(+), SO(+), NO(+)). Evidence supports naphthenic acids as among the most acutely toxic chemical classes in OSPW, but nonacidic species also contribute to acute toxicity of OSPW. PMID- 26381020 TI - Proteomic Investigation of Protein Profile Changes and Amino Acid Residue Level Modification in Cooked Lamb Meat: The Effect of Boiling. AB - Hydrothermal treatment (heating in water) is a common method of general food processing and preparation. For red-meat-based foods, boiling is common; however, how the molecular level effects of this treatment correlate to the overall food properties is not yet well-understood. The effects of differing boiling times on lamb meat and the resultant cooking water were here examined through proteomic evaluation. The longer boiling time was found to result in increased protein aggregation involving particularly proteins such as glyceraldehyde-3-phosphate dehydrogenase, as well as truncation in proteins such as in alpha-actinin-2. Heat induced protein backbone cleavage was observed adjacent to aspartic acid and asparagine residues. Side-chain modifications of amino acid residues resulting from the heating, including oxidation of phenylalanine and formation of carboxyethyllysine, were characterized in the cooked samples. Actin and myoglobin bands from the cooked meat per se remained visible on sodium dodecyl sulfate polyacrylamide gel electrophoresis, even after significant cooking time. These proteins were also found to be the major source of observed heat-induced modifications. This study provides new insights into molecular-level modifications occurring in lamb meat proteins during boiling and a protein chemistry basis for better understanding the effect of this common treatment on the nutritional and functional properties of red-meat-based foods. PMID- 26381021 TI - Evidence for Strong Electronic Correlations in the Spectra of Gate-Doped Single Wall Carbon Nanotubes. AB - We have investigated the photophysical properties of electrochemically gate-doped semiconducting single-wall carbon nanotubes (s-SWNTs). A comparison of photoluminescence (PL) and simultaneously recorded absorption spectra reveals that free-carrier densities correlate well with the first sub-band exciton or trion oscillator strengths but not with PL intensities. We thus used a global analysis of the first sub-band exciton absorption for a detailed investigation of gate-doping, here of the (6,5) SWNT valence band. Our data are consistent with a doping-induced valence band shift according to Deltaepsilonv = n * b, where n is the free-carrier density, epsilonv is the valence band edge, and b = 0.15 +/- 0.05 eV.nm. We also predict such band gap renormalization of one-dimensional gate doped semiconductors to be accompanied by a stepwise increase of the carrier density by Deltan = (32meffb)/(pih)(2) (meff is effective carrier mass). Moreover, we show that the width of the spectroelectrochemical window of the first sub-band exciton of 1.55 +/- 0.05 eV corresponds to the fundamental band gap of the undoped (6,5) SWNTs in our samples and not to the renormalized band gap of the doped system. These observations as well as a previously unidentified absorption band emerging at high doping levels in the Pauli-blocked region of the single-particle Hartree band structure provide clear evidence for strong electronic correlations in the optical spectra of SWNTs. PMID- 26381022 TI - Regional Variations in the Histology of the Skin. AB - In this article, we present a compendium of the most relevant histological features of the skin in terms of their regional variations along with histological clues that facilitate the topographic identification of cutaneous biopsies. PMID- 26381023 TI - The Incidence of Acantholysis in Pityriasis Rubra Pilaris-Histopathological Study Using Multiple-Step Sections and Clinicopathologic Correlations. AB - BACKGROUND: The classical histopathological findings in the epidermis of pityriasis rubra pilaris (PRP) do not include acantholysis; however, acantholysis was described in several case reports and a few series of PRP with variable frequencies. We sought to establish the incidence of acantholysis in biopsies from consecutively referred PRP cases using multiple-step sections and clinicopathologic correlations. METHODS: Twenty-three biopsies from 12 consecutively referred patients with classical (type 1) PRP were studied histopathologically. Each specimen was completely step sectioned. The clinical files of the patients were also reviewed. RESULTS: Small foci of acantholysis were observed in some of the step sections of 5 of 23 (22%) biopsies obtained from 4 patients. Three biopsies showed suprabasal acantholysis, 1 of which also demonstrated mild dyskeratosis and 2 showed midepidermal acantholytic foci as well. The remaining 2 biopsies demonstrated midepidermal and subcorneal acantholysis, respectively. Small erosions were described in the physical examination of 2 of the 4 (50%) patients with acantholysis and in 1 of the 8 (12.5%) patients without acantholysis. LIMITATIONS: The number of cases. CONCLUSIONS: Small foci of acantholysis may be found in the minority of PRP biopsies, and it may be related to small erosions clinically in some patients. PMID- 26381024 TI - Actinic Keratosis, Transected: What Lies Beneath? AB - Evaluation of superficial transected shave biopsies of squamous neoplasms often presents a diagnostic dilemma for the dermatopathologist because of the lack of complete visualization of the base of the epidermis. Fear of "missing" an invasive carcinoma must be balanced with avoidance of overdiagnosis of precancerous actinic keratosis (AK), especially on cosmetically sensitive areas such as the face. If a concern exists that a more invasive component may be present, a diagnosis of AK transected at the base (AKT) will often be rendered to alert the dermatologist of this concern. Because of lack of objective data regarding the malignant transformation of this diagnosis, the method of treatment is often based on the clinical appearance of the residual lesion or the lesion is rebiopsied to establish a more definitive diagnosis, costing patient and physician time and increasing health care costs. This study aims to provide objective data regarding (1) how often dermatologists are resampling these lesions and (2) how accurately an AKT diagnosis identifies patient risk for a more aggressive lesion, to establish whether there is a benefit in providing more tissue for the initial biopsy. We performed a retrospective study examining 274 biopsies with a diagnosis of AKT. We found only 27% had follow-up rebiopsy or excision. Of these 73 cases, 63% showed residual AK and 20% showed a more serious lesion, which warrants more aggressive treatment. Because the health care culture slowly shifts to metric-driven medicine and value-based payment, providing objective data for the progression of diagnosis, such as AKT, will be important (1) to aid the clinician in taking adequate tissue samples for diagnosis to make adequately informed management decisions, (2) to reduce the conversion of AK to squamous cell carcinoma, the resultant depth of squamous cell invasion, and the patient's risk of metastases to improve the patient's long-term outcomes, and (3) to decrease the overall cost of the patient's health care by improving the patient's long-term outcomes. PMID- 26381025 TI - CD4, IL-17, and COX-2 Are Associated With Subclinical Inflammation in Malar Melasma. AB - The pathogenesis of melasma, a common, photo-induced hyperpigmentary disorder, is not clearly understood. Significant factors linked to melasma are ultraviolet radiation exposure and genetic predisposition. Histological analysis has demonstrated that melasma is caused by a network of cellular interactions among melanocytes, keratinocytes, mast cells, fibroblasts, and dermal vasculature exhibits, features similar to chronic sun damage. Dermal inflammation caused by ultraviolet radiation might play an important role in the hyperpigmentation and reactivation of melasma lesions through the production of melanogenic cytokines and growth factors. Because the role of inflammation in this disorder is unknown, we used histochemistry, immunohistochemistry, and quantitative real-time polymerase chain reaction to evaluate melasma lesions from healthy female patients (n = 20) with malar melasma. Lesional skin without specific solar exposure or photoprotection measures within the previous 4 weeks was compared with nonlesional skin. The increased lymphocytic infiltrate in lesional skin was mainly composed of CD4 T cells, mast cells, and macrophages. Levels of the cytokine interleukin (IL)-17 and the proinflammatory mediator cyclooxygenase (COX)-2 were significantly elevated in affected skin compared with healthy skin. In addition, the Melasma Activity and Severity Index score, fraction of solar elastosis, and epidermal melanin were positively associated with COX-2 expression. There was no statistically significant difference in IL-1alpha, IL 1beta, R-IL1, IL-6, IL-8, vascular endothelial growth factor, and tumor necrosis factor alpha expression levels. Together, these data indicated that melasma under unchallenged conditions is characterized by chronic inflammatory cells and mediators, which may explain its recurrent nature. PMID- 26381026 TI - Occult Dermal Lymphatic Involvement Is Frequent in Primary Cutaneous Anaplastic Large Cell Lymphoma. AB - Primary cutaneous anaplastic large cell lymphoma (pcALCL) is an indolent T-cell lymphoproliferative disorder managed with low-dose radiation therapy, surgery, and/or mild chemotherapy; patients with extensive limb disease (ELD) have a more aggressive clinical course. We have previously demonstrated that histologically apparent vascular involvement in pcALCL is lymphatic. We hypothesized that histologically occult lymphatic involvement may be associated with particular patterns of disease spread that could involve lymphangitic spread including locoregional spread of disease in the form of ELD and extracutaneous spread of disease. We have therefore set out to quantitate the incidence of occult lymphovascular involvement in pcALCL and to assess for an association between lymphovascular involvement and these patterns of disease. We performed immunohistochemistry for the lymphovascular marker D2-40 on skin biopsies from 29 patients with pcALCL followed in the Stanford Cutaneous Lymphoma Clinic. Immunohistochemically evident dermal lymphovascular involvement was found in nearly half of cases examined (48%; 95% confidence interval, 29%-67%). There was a nonsignificant trend toward a higher prevalence of ELD among patients with pcALCL involving dermal lymphatics (7% vs. 29%; p = 0.12). In this small cohort, there was no indication of a significantly more aggressive disease course in patients with lymphatic involvement either in the form of disease-related mortality (one each in the lymphatic and nonlymphatic groups) or in time to extracutaneous involvement. PMID- 26381027 TI - Bright Red Papules in a HIV-Positive 20-Year-Old Man: Challenge. PMID- 26381028 TI - BRAF Inhibitor-Induced Antitumoral Granulomatous Dermatitis Eruption in Advanced Melanoma. AB - Recent advances in targeting BRAF mutations, which occur in roughly 50% of the melanomas, have improved response rates and overall survival in patients with advanced disease. With the increasingly extensive use of the drug, new, nonpreventable, cutaneous and noncutaneous toxicities keep arising as infrequent adverse effects. We report a 55-year-old man with a history of metastatic melanoma treated with the dabrafenib who presented, 10 months after the initiation of the treatment, with erythematous, slightly squamous, round plaques on his upper trunk and on his left upper arm. Two skin biopsies from the lesions revealed a granulomatous dermatitis in the superficial reticular dermis. One of them showed admixed abundant melanophages from tumoral melanosis. No melanoma cells were seen in any of the specimens. No interruption of the treatment was necessary. Our observation indicates that such a response may represent a positive immune activation triggered by BRAF inhibitors. The erythematous rash was initially concerning for progression of metastatic disease, which suggests that a close monitoring of the patients with advanced melanomas treated with vemurafenib is advisable to prevent unnecessary discontinuation of the therapy. PMID- 26381030 TI - Multispectral Imaging Approach to the Diagnosis of a CD20+ Cutaneous T-cell Lymphoproliferative Disorder: A Case Report. AB - Expression of the pan B-cell marker CD20 by T-cell lymphoproliferative disorders is exceedingly rare. We present a 52-year-old man with a unilesional cutaneous CD20 T-cell lymphoproliferative disorder. Multispectral imaging analysis of CD3 CD20 double-stained lesional tissue sections allowed (1) the visualization of double-positive T lymphocytes in situ with sensitivity superior to that of conventional immunohistochemistry and (2) the quantitative assessment of marker coexpression. Here, 23% of CD3 signals in the patient's lesion were also CD20, whereas 38% of CD20 signals were also CD3. In contrast, both parameters were below 1% in the tonsil control. Overall, the percentage of double-positive cells in lesional skin was 35%, although only 0.4% of such cells were detected in the tonsil. This is the first demonstration of aberrant CD20 expression by skin infiltrating T cells using multispectral imaging. PMID- 26381031 TI - Direct Antiglobulin Test Positivity in Children With Acute Lymphoblastic Leukemia at Diagnosis. AB - Direct antiglobulin test positivity had been reported in the course of some lymphoproliferative neoplasms. However, there are a few case reports describing direct antiglobulin test (DAT) positivity in children with acute lymphoblastic leukemia (ALL). We herein report 8 patients who had positive DAT among 95 newly diagnosed children with ALL. None of these patients had evidence of hemolysis during the follow-up. An antibody was detected in 2 of 8 patients with positive DAT. These 2 children also had positive indirect antiglobulin test (IAT); an autoantibody that was reactive at 4 degrees C, and an alloantibody (anti E) that was reactive at 37 degrees C was detected. We believe DAT positivity in ALL without significant hemolysis is not a rare disorder, and a need for further prospective studies is apparent. PMID- 26381033 TI - What does fetal autopsy unmask in oligohydramnios? AB - OBJECTIVE: We aimed to determine the value of autopsy in fetuses with antenatally diagnosed oligohydramnios. PATIENTS AND METHODS: We evaluated all fetal losses over a period of 6.5 years. Those with oligohydramnios on antenatal scan were critically analyzed. Oligohydramnios was defined as amniotic fluid index of less than five objectively or as an obvious lack of liquor at subjective assessment. A detailed postmortem examination was carried out in all the fetuses after obtaining an informed consent. RESULTS: Fetal autopsy was conducted in 255 cases. Fifty-five (21.5%) fetuses were diagnosed to have oligohydramnios on antenatal ultrasonography. On analysis of antenatal causes of oligohydramnios, maternal/placental factors were noted in 18%, ultrasound findings known to affect amniotic fluid in 27% while cause remained unidentified in 54.5% of cases. On autopsy, fetal malformations were noted in 61.8% cases, intrauterine growth retardation in 21.8% fetuses and no obvious malformations in 16.3% fetuses. Renal anomalies were noted in 40% cases and non-renal malformations in 21.8% cases. CONCLUSION: The postmortem examination helped us to identify the cause of fetal loss in 46 (83.6%) fetuses with antenatal oligohydramnios. A working diagnosis could not have been established without autopsy in 19 (34.5%) cases. PMID- 26381032 TI - AP-1-Targeted Inhibition of Macrophage Function and Lipopolysaccharide/D Galactosamine-Induced Hepatitis by Phyllanthus acidus Methanolic Extract. AB - Traditionally, Phyllanthus acidus (Phyllanthaceae) has been used for the treatment of rheumatism, bronchitis, asthma, respiratory disorders, and hepatitis. Recently, we showed that a methanol extract of Phyllanthaceae (Pa-ME) has a potent anti-inflammatory activity in RAW264.7 cells and strongly ameliorates HCl / EtOH -induced gastric ulcers in mice by targeting the Src/Syk of NF-kappaB. In the present study, we explored the molecular mechanism of Pa-ME on the AP-1 activation pathway and evaluated its potential hepatoprotective effects. To do this, we employed lipopolysaccharide (LPS)-stimulated RAW264.7 cells and U937 cells and an LPS/D-galactosamine (D- GaIN )-induced acute hepatitis mouse model. We utilized a multitude of assays, including immunoblotting analysis, reporter gene assays, and mRNA expression analysis, to determine the effect of Pa-ME on the AP-1 pathway. Pa-ME strikingly suppressed the production of LPS-induced pro-inflammatory cytokines including interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha (TNF-alpha). Furthermore, Pa-ME also strongly inhibited activator protein-1 (AP-1) activation and mitogen activated protein kinase (MAPK) phosphorylation in LPS-stimulated RAW264.7 macrophages cells and the U937 monocyte like human cell line. Moreover, pre treatment with Pa-ME exhibited strong hepatoprotective and curative effects in an LPS/D-Gal-induced mouse hepatitis model as evidenced by a decrease in elevated serum AST and ALT levels and the amelioration of histological damage. Taken together, our data suggest that Pa-ME might play a crucial ethnopharmacological role as a hepatoprotective herbal remedy by suppressing MAPK signaling and the activity of the downstream transcription factor AP-1. PMID- 26381034 TI - Effect of Glucose on GLUT1-Dependent Intracellular Ascorbate Accumulation and Viability of Thyroid Cancer Cells. AB - Enhanced glucose requirement of cancer cells is associated with an increased glucose transport across plasma membrane that is mediated by a family of facilitated glucose transporter proteins, named GLUTs. GLUT1 is the main transporter in thyroid cancer cells. Glucose is the principal physiological substrate of GLUT1; however, it is also capable of transporting of oxidized form of vitamin C [i.e., dehydroascorbic acid (DHAA) which inside the cells is reduced to ascorbic acid (AA)]. The objective of this study was to determine the effect of normo-, hypo-, and hyperglycemia conditions on GLUT1-dependent intracellular ascorbate accumulation and viability of thyroid cancer cells. GLUT1 seems to be the main DHAA transporter in thyroid cancer cells because its knockdown by RNAi reduced DHAA accumulation by more than 80%. The results showed that in thyroid cancer cells high glucose inhibits both transport of AA and DHAA. Inhibition of vitamin C transport by glucose had a cytotoxic effect on the cells. However, stabilization of vitamin C in one of 2 forms (i.e., AA or DHAA) abolished this effect. These results suggest that cytotoxic effect is rather associated with extracellular accumulation of vitamin C and changes of its oxidation state than with intracellular level of ascorbate. PMID- 26381035 TI - Metagenomics for the development of new biocatalysts to advance lignocellulose saccharification for bioeconomic development. AB - The world economy is moving toward the use of renewable and nonedible lignocellulosic biomasses as substitutes for fossil sources in order to decrease the environmental impact of manufacturing processes and overcome the conflict with food production. Enzymatic hydrolysis of the feedstock is a key technology for bio-based chemical production, and the identification of novel, less expensive and more efficient biocatalysts is one of the main challenges. As the genomic era has shown that only a few microorganisms can be cultured under standard laboratory conditions, the extraction and analysis of genetic material directly from environmental samples, termed metagenomics, is a promising way to overcome this bottleneck. Two screening methodologies can be used on metagenomic material: the function-driven approach of expression libraries and sequence driven analysis based on gene homology. Both techniques have been shown to be useful for the discovery of novel biocatalysts for lignocellulose conversion, and they enabled identification of several (hemi)cellulases and accessory enzymes involved in (hemi)cellulose hydrolysis. This review summarizes the latest progress in metagenomics aimed at discovering new enzymes for lignocellulose saccharification. PMID- 26381036 TI - Effect of Peritoneal Lavage with Clindamycin-Gentamicin Solution during Elective Colorectal Cancer Surgery on the Oncologic Outcome. AB - BACKGROUND: Antibiotics combined with lavage have demonstrated a reduction in the bacterial contamination and decreases surgical site infection (SSI) rate. SSI leads to an immunocompromised situation, as immunologic defense is focused on controlling the septic focus, leaving unattended the neoplasm. It has been described that SSI may result in a worse oncologic outcome. The aim of this study is to evaluate prospectively the effect of peritoneal lavage with clindamycin and gentamicin on the oncologic outcome of colorectal tumors. METHODS: A randomized study of patients with diagnosis of colorectal neoplasms and undergoing elective surgery was performed at our institutions between January and September 2011. Patients were randomly assigned into two groups: Those undergoing an intra abdominal lavage with normal saline (Group 1) and those undergoing an intra abdominal lavage with a gentamicin-clindamycin solution (Group 2). Recurrence, global survival, and disease-free survival were investigated. RESULTS: One hundred and four patients were analyzed, with 52 in each group. After a minimum follow-up of 42 mo, mean disease-free survival was 37.2 +/- 14.2 mo in Group 1 and 25.8 +/- 16.3 mo in Group 2 (mean difference 11.4; confidence interval (CI) 95% (2.2-25.1); p = 0.009). Mean global survival was 44.2 +/- 11.9 mo in Group 1 and 34.1 +/- 14.1 mo in Group 2 (mean difference 10.1; CI 95% (2.2-18);p = 0.016). CONCLUSION: The intra-peritoneal lavage with gentamicin and clindamycin increases the disease-free and global survival colorectal tumors. PMID- 26381037 TI - Can We Provide Low Intrarenal Pressures with Good Irrigation Flow by Decreasing the Size of Ureteral Access Sheaths? AB - BACKGROUND AND PURPOSE: Flexible ureterorenoscopy (F-URS) plays a major role in the management of kidney stones. Ureteral access sheaths (UAS) are important tools for F-URS. In this study, we aimed to evaluate the difference in intrarenal pressures between different flexible ureteroscopes while using the same UAS and to calculate the irrigation flow variance. MATERIALS AND METHODS: Eight different flexible ureteroscopes were tested with five different UAS on an artificial kidney model to measure intrarenal pressures and irrigation flow. Irrigation at 60 cmH2O pressure was performed; the pressure and the irrigation flow amount were recorded with different states of the operator channel: Free, with the laser fiber (272 MUm), and with the nitinol basket (1.9F) inside. RESULTS: The highest pressure recorded was 46.68 cmH2O with Wolf Boa and 9.5/11.5F Cook Medical UAS. All the ureteroscopes that fit inside the 10/12F Coloplast ReTrace provided pressures below 40 cmH2O. The inner diameter of the 10/12F Rocamed Bi-Flex is actually 11F, so intrarenal pressures were lower and irrigation flow was higher. With the 11/13F Boston Scientific Navigator HD and 12/14F Coloplast ReTrace, the pressures were very low. The irrigation flow measurements were in concordance with pressure measurements. CONCLUSION: The ureteroscope sizes diminished with advancements in technology. Small-sized ureteroscopes can provide low intrarenal pressures with good irrigation flow when used with convenient small-sized access sheaths. The compatibility between the ureteroscopes and UASs should be anticipated by all endourologists and considered during F-URS. The advantages of 10/12 UASs in terms of intrarenal pressure and irrigational flow should make these access sheaths an interesting first-line choice. PMID- 26381038 TI - Metabolic Youth in Middle Age: Predicting Aging in Caenorhabditis elegans Using Metabolomics. AB - Many mutations and allelic variants are known that influence the rate at which animals age, but when in life do such variants diverge from normal patterns of aging? Is this divergence visible in their physiologies? To investigate these questions, we have used (1)H NMR spectroscopy to study how the metabolome of the nematode Caenorhabditis elegans changes as it grows older. We identify a series of metabolic changes that, collectively, predict the age of wild-type worms. We then show that long-lived mutant daf-2(m41) worms are metabolically youthful compared to wild-type worms, but that this relative youth only appears in middle age. Finally, we show that metabolic age predicts the timing and magnitude of differences in age-specific mortality between these strains. Thus, the future mortality of these two genotypes can be predicted long before most of the worms die. PMID- 26381039 TI - Activated Conventional T-Cells Are Present in Langerhans Cell Histiocytosis Lesions Despite the Presence of Immune Suppressive Cytokines. AB - Langerhans cell histiocytosis (LCH) lesions are characterized by neoplastic CD1a(+)/Langerin(+) histiocytes (LCH-cells) and display many features of chronic inflammation. Cancer cells can escape immune-surveillance through intra-tumoral secretion of immune-suppressive cytokines. We therefore studied by immunohistochemistry the local cytokine milieu and phenotypic characteristics of T-cells and LCH-cells present in LCH lesions collected from 25 therapy naive patients. LCH biopsies predominantly expressed interleukin-10 (IL-10) (10/25), transforming growth factor-beta (TGF-beta) (9/25), or both cytokines (6/25). The absolute number of CD3(+)T-cells and the CD3(+)FOXP3(-) conventional cell (T CONV) versus the CD3(+)FOXP3(+) regulatory T-cell (T-REG) was comparable for each suppressive cytokine profile (5:1). IL-10-expressing lesions contained, however, a higher proportion of T-CONV expressing the activation markers CD25 98% (38% 100%) and inducible costimulatory molecule (ICOS) 86% (47%-100%) than lesions wherein solely TGF-beta was detected (CD25(+) 20% (6%-54%); ICOS(+) 29% (7% 51%)). Virtually all T-REG expressed CD25 and ICOS in IL-10 lesions, whereas TGF beta(+) lesions contained a lower proportion of ICOS(+) T-REG (P=0.05). IL-10(+) lesions contained more LCH-cells expressing high intensity of ICOS ligand (ICOSL) compared with TGF-beta(+) lesions (P=0.03). ICOS expression by lesion infiltrating T-CONV and T-REG positively correlated to the extent of ICOSL expression by LCH-cells (P=0.004). Our study points out that the combined detection of interlesional IL-10 and ICOSL expression by LCH-cells is associated with the highest prevalence of activated T-CONV. Immune profiling of LCH-affected tissues obtained at the time of diagnosis may set the stage for the development of new types of therapies, which aim at local boosting of immune cells that recognize and eliminate neoplastic LCH-cells. PMID- 26381040 TI - Low-dose cyclophosphamide effectively mobilizes peripheral blood stem cells in patients with autoimmune disease. AB - For patients with severe and refractory autoimmune diseases, high-dose chemotherapy and autologous hematopoietic stem cell transplantation has been established as a considerable therapeutic option in recent years. In this retrospective single-center analysis, we assessed the feasibility and efficacy of peripheral blood stem cells (PBSC) mobilization and collection in 35 patients with refractory autoimmune disease (AID). The mobilization data of 15 patients with systemic sclerosis (SSc), 11 patients with multiple sclerosis (MS), and 9 patients with other AID were analyzed. Stem cell mobilization with cyclophosphamide chemotherapy 2 * 2 g/m(2) (n = 16) or 1 * 2 g/m(2) (n = 17) and G-CSF followed by PBSC collection was performed between 1999 and 2015. Leukapheresis was performed in 16 inpatients and 19 outpatients. All patients reached their collection goal and no collection failures were observed. The median PBSC collection result was 12.2 (SSc), 8.0 (MS), and 8.2 (other AID) * 10(6) CD34+ cells/kg, respectively. Twenty-five of 35 (71%) patients achieved a sufficient collection with one leukapheresis session, while 6 patients (17%) required two and 4 patients (11%) required three or more leukapheresis sessions. No correlation of the collected PBSC number was observed regarding age, body weight, diagnosis, disease duration, skin sclerosis, or previous cyclophosphamide. Mobilization chemotherapy with cyclophosphamide 2 * 2 g/m(2) and 1 * 2 g/m(2) delivered comparable mobilization results with leukapheresis on day 13 or 14. In summary, we demonstrate that PBSC collection is safe and feasible in patients with AID. Mobilization chemotherapy with cyclophosphamide 1 * 2 g/m(2) and 2 * 2 g/m(2) is equally effective in those patients. PMID- 26381041 TI - Antiviral therapy and hepatocellular carcinogenesis. PMID- 26381042 TI - Loss of ACSS2 expression predicts poor prognosis in patients with gastric cancer. AB - BACKGROUND: Recent studies have demonstrated that acetyl-CoA synthetase 2 (ACSS2) plays a critical role in cancer cell survival; however, the role of ACSS2 in gastric carcinogenesis has not been determined. METHODS: We investigated the expression of ACSS2 in human gastric cancer (GC) tissues using immunohistochemistry, and analyzed its clinicopathological correlation and prognostic relevance. RESULTS: Among 350 GCs, 219 cases (62.6%) were classified as ACSS2-low, whereas 131 cases (37.4%) were ACSS2-high. Loss of ACSS2 expression (ACSS2-low) was more frequently observed in undifferentiated histology (P = 0.002), in cases with MLH1-loss (P = 0.003), and in cases with SIRT3-low (P < 0.001). The ACSS2-low cases showed significantly lower mean disease-free survival (DFS, 68.5 vs. 81.8 months; P = 0.025) and overall survival (OS, 73.5 vs. 86.6 months; P = 0.029). In multivariate analysis, loss of ACSS2 expression was identified as one of the independent prognostic factors predicting worse DFS (HR: 1.547, P = 0.018) and OS (HR: 1.476, P = 0.036). CONCLUSIONS: We revealed that the loss of ACSS2 expression is a reliable independent poor prognostic factor in GC. Our results may expand our understanding of the involvement of glucose metabolism, including the role of ACSS2, in the pathogenesis of GC. PMID- 26381043 TI - Expanding the Reach of Participatory Risk Management: Testing an Online Decision Aiding Framework for Informing Internally Consistent Choices. AB - This article presents research aimed at developing and testing an online, multistakeholder decision-aiding framework for informing multiattribute risk management choices associated with energy development and climate change. The framework was designed to provide necessary background information and facilitate internally consistent choices, or choices that are in line with users' prioritized objectives. In order to test different components of the decision aiding framework, a six-part, 2 * 2 * 2 factorial experiment was conducted, yielding eight treatment scenarios. The three factors included: (1) whether or not users could construct their own alternatives; (2) the level of detail regarding the composition of alternatives users would evaluate; and (3) the way in which a final choice between users' own constructed (or highest-ranked) portfolio and an internally consistent portfolio was presented. Participants' self-reports revealed the framework was easy to use and providing an opportunity to develop one's own risk-management alternatives (Factor 1) led to the highest knowledge gains. Empirical measures showed the internal consistency of users' decisions across all treatments to be lower than expected and confirmed that providing information about alternatives' composition (Factor 2) resulted in the least internally consistent choices. At the same time, those users who did not develop their own alternatives and were not shown detailed information about the composition of alternatives believed their choices to be the most internally consistent. These results raise concerns about how the amount of information provided and the ability to construct alternatives may inversely affect users' real and perceived internal consistency. PMID- 26381044 TI - The immunological barriers to xenotransplantation. AB - The availability of cells, tissues and organs from a non-human species such as the pig could, at least in theory, meet the demand of organs necessary for clinical transplantation. At this stage, the important goal of getting over the first year of survival has been reported for both cellular and solid organ xenotransplantation in relevant preclinical primate models. In addition, xenotransplantation is already in the clinic as shown by the broad use of animal derived medical devices, such as bioprosthetic heart valves and biological materials used for surgical tissue repair. At this stage, however, prior to starting a wide-scale clinical application of xenotransplantation of viable cells and organs, the important obstacle represented by the humoral immune response will need to be overcome. Likewise, the barriers posed by the activation of the innate immune system and coagulative pathway will have to be controlled. As far as xenogeneic nonviable xenografts, increasing evidence suggests that considerable immune reactions, mediated by both innate and adaptive immunity, take place and influence the long-term outcome of xenogeneic materials in patients, possibly precluding the use of bioprosthetic heart valves in young individuals. In this context, the present article provides an overview of current knowledge on the immune processes following xenotransplantation and on the possible therapeutic interventions to overcome the immunological drawbacks involved in xenotransplantation. PMID- 26381046 TI - Sequence variations of the locus-specific 5' untranslated regions of SLA class I genes and the development of a comprehensive genomic DNA-based high-resolution typing method for SLA-2. AB - The genetic diversity of the major histocompatibility complex (MHC) class I molecules of pigs has not been well characterized. Therefore, the influence of MHC genetic diversity on the immune-related traits of pigs, including disease resistance and other MHC-dependent traits, is not well understood. Here, we attempted to develop an efficient method for systemic analysis of the polymorphisms in the epitope-binding region of swine leukocyte antigens (SLA) class I genes. We performed a comparative analysis of the last 92 bp of the 5' untranslated region (UTR) to the beginning of exon 4 of six SLA classical class I related genes, SLA-1, -2, -3, -4, -5, and -9, from 36 different sequences. Based on this information, we developed a genomic polymerase chain reaction (PCR) and direct sequencing-based comprehensive typing method for SLA-2. We successfully typed SLA-2 from 400 pigs and 8 cell lines, consisting of 9 different pig breeds, and identified 49 SLA-2 alleles, including 31 previously reported alleles and 18 new alleles. We observed differences in the composition of SLA-2 alleles among different breeds. Our method can be used to study other SLA class I loci and to deepen our knowledge of MHC class I genes in pigs. PMID- 26381048 TI - Identification of a novel allele: DQB1*06:127 in Hispanic sisters. AB - Newly identified allele, HLA-DQB1*06:127, differs from DQB1*06:02:01 by the single nucleotide substitution 426C-A at codon 110 in exon 3. PMID- 26381047 TI - The interaction of genetic determinants in the outcome of HCV infection: evidence for discrete immunological pathways. AB - Diversity within the innate and adaptive immune response to hepatitis C is important in determining spontaneous resolution (SR) and treatment response. The aim of this study was to analyze how these variables interact in combination; furthering our understanding of the mechanisms that drive successful immunological clearance. Multivariate analysis was performed on retrospectively collected data for 357 patients previously genotyped for interferon (IFN) lambda3/4, killer cell immunoglobulin (KIR), human leukocyte antigen (HLA) class I and II and tapasin. High resolution KIR genotyping was performed for individuals with chronic infection and haplotypes determined. Outcomes for SR, IFN response and cirrhosis were examined. Statistical analysis included univariate methods, chi(2) test for trend, multivariate logistic regression, synergy and principal component analysis (PCA). Although KIR2DL3:HLA-C1C1 (P = 0.027), IFN-lambda3/4 rs12979860 CC (P = 0.027), tapasin G in individuals with aspartate at residue 114 of HLA-B (TapG:HLA-B(114D) ) (P = 0.007) and HLA DRB1*04:01 (P = 0.014) were associated with SR with a strong additive influence (chi(2) test for trend P < 0.0001); favorable polymorphisms did not interact synergistically, nor did patients cluster by outcome. In the treatment cohort, IFN-lambda3/4 rs12979860 CC was protective in hepatitis C virus (HCV) G1 infection and KIR2DL3:HLA-C1 in HCV G2/3. In common with SR, variables did not interact synergistically. Polymorphisms predictive of viral clearance did not predict disease progression. In summary, different individuals resolve HCV infection using discrete and non-interacting immunological pathways. These pathways are influenced by viral genotype. This work provides novel insights into the complexity of the interaction between host and viral factors in determining the outcome of HCV infection. PMID- 26381049 TI - A novel HLA allele, HLA-DRB1*13:204, detected in a Brazilian unrelated hematopoietic stem cell donor. AB - The HLA-DRB1*13:204 allele differs from HLA*13:64 by two nucleotide substitutions at positions 181 and 189 in the exon 2. PMID- 26381050 TI - FTIR and SEM analysis applied in tissue engineering for root recovering surgery. AB - Gingival recession is defined by the displacement of the gingival margin in the apical direction, which overcomes the cementum enamel junction. The etiology of gingival retraction is related to tissue inflammation caused by the accumulation of biofilm, by trauma from brushing action. Aesthetic periodontal surgery aims to return the root coverage to aesthetic harmony, and reduce the risk of periodontal disease and caries. To assist in the root coverage process, the porcine collagen matrix (PCM) has been widely studied. The objectives of this study are to identify the types of collagen that make up the PCM and analyze their morphology. For this, five PCM fragments, 2 mm (thickness) * 2.6 mm (width), were analyzed with the aid of scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). The analysis by SEM showed that the PCM consists of two layers; the surface layer is compact, low porosity, and smooth surface, and a foamed underlying layer has high porosity. Through FTIR we identified that the surface and underlying layers are composed of collagen types I and III, respectively. This biomaterial is conducive to root coverage; it allows adsorption and cell proliferation following the matrix resorption and periodontal tissue neoformation. (c) 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1326-1329, 2017. PMID- 26381052 TI - A comprehensive study of the (2?3 * 2?3)R30 degrees structure of silicene on Ag(1 1 1). AB - The deposition of one silicon monolayer on Ag(1 1 1) gives rise to a set of superstructures depending on growth conditions. These superstructures are correlated to the epitaxy between the honeycomb structure of silicon (so called silicene) and the silver substrate. In this paper, from a detailed re-analysis of experimental results, obtained by scanning tunneling microscopy and by low energy electron diffraction on the (2?3 * 2?3)R30 degrees structure, we propose a new atomic model of the silicene layer based on periodic arrangements of perfect areas of (2?3 * 2?3)R30 degrees surrounded by defect areas. A generalization of this model explains the main experimental observations: deviation of the average direction, Moire patterns and apparent global disorder. In the frame of the proposed model, the apparent disorders observed on the STM images, would be topological effects, i.e. the silicene would keep a quasi-perfect honeycomb structure. PMID- 26381051 TI - Regulation of cardiac miR-208a, an inducer of obesity, by rapamycin and nebivolol. AB - OBJECTIVE: Resistance to obesity is observed in rodents and humans treated with rapamycin (Rap) or nebivolol (Neb). Because cardiac miR-208a promotes obesity, this study tested whether the modes of actions of Rap and Neb involve inhibition of miR-208a. METHODS: Mouse cardiomyocyte HL-1 cells and Zucker obese (ZO) rats were used to investigate regulation of cardiac miR-208a. RESULTS: Angiotensin II (Ang II) increased miR-208a expression in HL-1 cells. Pretreatment with an AT1 receptor (AT1R) antagonist, losartan (1 MUM), antagonized this effect, whereas a phospholipase C inhibitor, U73122 (10 MUM), and an NADPH oxidase inhibitor, apocynin (0.5 mM), did not. Ang II-induced increase in miR-208a was suppressed by Rap (10 nM), an inhibitor of nutrient sensor kinase mTORC1, and Neb (1 MUM), a 3rd generation beta-blocker that suppressed bioavailable AT1R binding of (125) I Ang II. Thus, suppression of AT1R expression by Neb, inhibition of AT1R activation by losartan, and inhibition of AT1R-induced activation of mTORC1 by Rap attenuated the Ang II-induced increase in miR-208a. In ZO rats, Rap treatment (750 MUg kg(-1) day(-1) ; 12 weeks) reduced obesity despite similar food intake, suppressed cardiac miR-208a, and increased cardiac MED13, a suppresser of obesity. CONCLUSIONS: Rap and Neb suppressed cardiac miR-208a. Suppression of miR 208a and increase in MED13 correlated with attenuated weight gain despite leptin resistance. PMID- 26381053 TI - The Severity and Pattern of Autonomic Dysfunction in Idiopathic Rapid Eye Movement Sleep Behavior Disorder. AB - BACKGROUND: Autonomic dysfunction in idiopathic rapid eye movement sleep behavior disorder patients has not yet been quantified. The aim of this study was to characterize dysautonomia in patients with idiopathic rapid eye movement sleep behavior disorder using the Composite Autonomic Severity Score, which is a validated instrument for the quantitation of autonomic failure. METHODS: We prospectively enrolled patients with idiopathic rapid eye movement sleep behavior disorder. A battery of standardized autonomic function tests was performed. Autonomic data obtained from the patients were compared to age- and sex-matched healthy controls. RESULTS: Seventeen patients were enrolled. All but 1 patient showed at least one autonomic deficit. These deficits were predominantly adrenergic and cardiovagal and involved relatively few sudomotor problems. The degree of autonomic dysfunction according to the Composite Autonomic Severity Score was mild to moderate in most patients. CONCLUSIONS: Idiopathic rapid eye movement sleep behavior disorder is linked to mild-to-moderate autonomic dysfunction, which is predominantly adrenergic and cardiovagal. PMID- 26381054 TI - Lack of Pharmacokinetic Interactions Between Macitentan and a Combined Oral Contraceptive in Healthy Female Subjects. AB - Macitentan, a dual endothelin receptor antagonist used in pulmonary arterial hypertension, induces cytochrome P450 (CYP) 3A at supratherapeutic concentrations in vitro. Most combined oral hormonal contraceptives (OCs) are CYP3A substrates and their efficacy can be affected by CYP3A inducers. This randomized crossover study assessed possible pharmacokinetic (PK) interactions between macitentan and an OC containing ethinyl estradiol and norethindrone (or norethisterone). Twenty six healthy women received a single oral dose of OC alone (reference) and concomitantly with 10 mg macitentan at steady state (test). No PK interaction was concluded if the 90% confidence intervals (CIs) of geometric mean ratios (GMRs; test/reference) of the peak plasma concentration (Cmax ) and the exposure from 0 to infinity (AUC0 - infinity ) to the OC components were within the equivalence limits of 0.8 to 1.25. Cmax and AUC0-infinity of the OC were within the equivalence limits. For ethinyl estradiol, GMRs (90%CIs) of Cmax and AUC0 infinity were 0.92 (0.85-0.99) and 0.95 (0.90-0.99). For norethindrone, these values were 1.02 (0.95-1.09) and 1.04 (0.98-1.09), respectively. Overall, study treatments were well tolerated. No major changes from baseline in safety parameters were reported in either treatment. Macitentan does not affect the PK of OCs. PMID- 26381055 TI - Phase Diagram Characterization Using Magnetic Beads as Liquid Carriers. AB - Magnetic beads with ~1.9 um average diameter were used to transport microliter volumes of liquids between contiguous liquid segments with a tube for the purpose of investigating phase change of those liquid segments. The magnetic beads were externally controlled using a magnet, allowing for the beads to bridge the air valve between the adjacent liquid segments. A hydrophobic coating was applied to the inner surface of the tube to enhance the separation between two liquid segments. The applied magnetic field formed an aggregate cluster of magnetic beads, capturing a certain liquid amount within the cluster that is referred to as carry-over volume. A fluorescent dye was added to one liquid segment, followed by a series of liquid transfers, which then changed the fluorescence intensity in the neighboring liquid segment. Based on the numerical analysis of the measured fluorescence intensity change, the carry-over volume per mass of magnetic beads has been found to be ~2 to 3 ul/mg. This small amount of liquid allowed for the use of comparatively small liquid segments of a couple hundred microliters, enhancing the feasibility of the device for a lab-in-tube approach. This technique of applying small compositional variation in a liquid volume was applied to analyzing the binary phase diagram between water and the surfactant C12E5 (pentaethylene glycol monododecyl ether), leading to quicker analysis with smaller sample volumes than conventional methods. PMID- 26381056 TI - SN-38 active loading in poly(lactic-co-glycolic acid) nanoparticles and assessment of their anticancer properties on COLO-205 human colon adenocarcinoma cells. AB - SN-38 is a highly effective drug against many cancers. The development of an optimal delivery system for SN-38 is extremely challenging due to its low solubility and labile lactone ring. Herein, SN-38 encapsulated in poly(D,L lactide-co-glycolide) nanoparticles (NPs) is introduced to enhance its solubility, stability and cellular uptake. SN-38-loaded NPs prepared by spontaneous emulsification solvent diffusion (SESD) method had an average diameter of 310 nm, a zeta potential of -9.69 mV and a loading efficiency of 71%. They were able to protect the active lactone ring of SN-38 against inactivation under physiological condition. A colorectal adenocarcinoma cell line (COLO-205) was used to assess the NPs effects on cytotoxicity and cellular uptake. Result showed a significant decreased cell proliferation and cell apoptosis. These results suggest that these SN-38-loaded NPs can be an effective delivery system for the treatment of colon cancer and potentially for other types of cancers. PMID- 26381057 TI - MTB-DR-RIF 9G test: Detection and discrimination of tuberculosis and multi-drug resistant tuberculosis strains. AB - This report describes the evaluation of the novel MTB-DR-RIF 9G test for the accurate detection and discrimination of Mycobacterium tuberculosis (MTB) and rifampicin-resistant M. tuberculosis (MTB-DR-RIF) in the clinical samples. The procedure included the amplification of a nucleotide fragment of the rpoB gene of the MTB and MTB-DR-RIF strains and their hybridization with the immobilized probes. The MTB-DR-RIF 9G test was evaluated for its ability to detect and discriminate MTB and MTB-DR-RIF strains in 113 known clinical samples. The accuracy of the MTB-DR-RIF 9G test was determined by comparing its results with sequencing analysis and drug susceptibility testing. The sensitivity and specificity of the MTB-DR-RIF 9G test at 95% confidence interval were found to be 95.4% (89.5-98.5) and 100% (69.2-100), respectively. The positive predictive value and negative predictive value of the MTB-DR-RIF 9G test at 95% confidence interval were found to be 100% (85.0-95.9) and 66.7% (38.4-88.18), respectively. Sequencing analysis of all samples indicated that the mutations present in the regions identified with the MTB-DR-RIF 9G assay can be detected accurately. PMID- 26381058 TI - Comparative Accuracy of Facial Models Fabricated Using Traditional and 3D Imaging Techniques. AB - PURPOSE: The purpose of this investigation was to compare the accuracy of facial models fabricated using facial moulage impression methods to the three dimensional printed (3DP) fabrication methods using soft tissue images obtained from cone beam computed tomography (CBCT) and 3D stereophotogrammetry (3D-SPG) scans. MATERIALS AND METHODS: A reference phantom model was fabricated using a 3D SPG image of a human control form with ten fiducial markers placed on common anthropometric landmarks. This image was converted into the investigation control phantom model (CPM) using 3DP methods. The CPM was attached to a camera tripod for ease of image capture. Three CBCT and three 3D-SPG images of the CPM were captured. The DICOM and STL files from the three 3dMD and three CBCT were imported to the 3DP, and six testing models were made. Reversible hydrocolloid and dental stone were used to make three facial moulages of the CPM, and the impressions/casts were poured in type IV gypsum dental stone. A coordinate measuring machine (CMM) was used to measure the distances between each of the ten fiducial markers. Each measurement was made using one point as a static reference to the other nine points. The same measuring procedures were accomplished on all specimens. All measurements were compared between specimens and the control. The data were analyzed using ANOVA and Tukey pairwise comparison of the raters, methods, and fiducial markers. RESULTS: The ANOVA multiple comparisons showed significant difference among the three methods (p < 0.05). Further, the interaction of methods versus fiducial markers also showed significant difference (p < 0.05). The CBCT and facial moulage method showed the greatest accuracy. CONCLUSIONS: 3DP models fabricated using 3D-SPG showed statistical difference in comparison to the models fabricated using the traditional method of facial moulage and 3DP models fabricated from CBCT imaging. 3DP models fabricated using 3D-SPG were less accurate than the CPM and models fabricated using facial moulage and CBCT imaging techniques. PMID- 26381059 TI - Another Look at the PART-O Using the Traumatic Brain Injury Model Systems National Database: Scoring to Optimize Psychometrics. AB - OBJECTIVE: To integrate previous approaches to scoring the Participation Assessment with Recombined Tools-Objective (PART-O) in a unidimensional scale. DESIGN: Retrospective analysis of PART-O data from the Traumatic Brain Injury Model Systems. SETTING: Community. PARTICIPANTS: Data from individuals (N=469) selected randomly from participants who completed 1-year follow-up in the Traumatic Brain Injury Model Systems were used in Rasch model development. The model was subsequently tested on data from additional random samples of similar size at 1-, 2-, 5-, 10-, and >15-year follow-ups. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: PART-O. RESULTS: After combining items for productivity and social interaction, the initial analysis at 1-year follow-up indicated relatively good fit to the Rasch model (person reliability=.80) but also suggested item misfit and that the 0-to-5 scale used for most items did not consistently show clear separation between rating levels. Reducing item rating scales to 3 levels (except combined and dichotomous items) resolved these issues and demonstrated good item level discrimination, fit, and person reliability (.81), with no evidence of multidimensionality. These results replicated in analyses at each additional follow-up period. CONCLUSIONS: Modifications to item scoring for the PART-O resulted in a unidimensional parametric equivalent measure that addresses previous concerns about competing item relations, and it fit the Rasch model consistently across follow-up periods. The person-item map shows a progression toward greater community participation from solitary and dyadic activities, such as leaving the house and having a friend through social and productivity activities, to group activities with others who share interests or beliefs. PMID- 26381060 TI - HIV-1 Thai B strain has spread out of former plasma donors into general population through sexual contact in Henan, China. AB - Henan, China is characterized by the outbreak of HIV epidemic of Thai B strain in former plasma donors in 1990s. After the forbidden of paid blood donation, whether Thai B strain will spread out of former plasma donors into sexual transmitted population is unknown. To answer the question, phylogenetic analysis was used to explore relationships of HIV strains circulating in those two populations in the study. HIV-1 sero-positive drug-naive patients infected through sexual contact were enrolled into the study. Full length gag and pol genes were amplified with nested RT-PCR followed by sequencing and phylogenetic analysis. The genotypes of anti-HIV drug resistance were also analyzed with available pol genes. HIV subtypes were determined in 249 individuals from 288 participants. Subtype B was dominant (202/249, 81.1%), followed by CRF01_AE (25/249, 10.0%), CRF07_BC (14/249, 5.6%), C (4/249, 1.6%), URF (3/249, 1.2%), and CRF08_BC (1/249, 0.4%). Most of subtype B strains belong to Thailand B lineage. All of Thai B strains identified in sexual transmitted population intermixed with those from former blood donors in phylogenetic tree, suggesting close phylogenetic relationship between strains epidemic in those two populations. TDR was identified in 9.9% individuals. Thai B strain has spread out of former blood donors in Henan province. The finding will contribute to understanding the distribution and evolution of HIV-1 in Henan province and also provide clue to behavior change intervention. PMID- 26381061 TI - Combined electrophysiological and biosensor approaches to study purinergic regulation of epileptiform activity in cortical tissue. AB - BACKGROUND: Cortical brain slices offer a readily accessible experimental model of a region of the brain commonly affected by epilepsy. The diversity of recording techniques, seizure-promoting protocols and mutant mouse models provides a rich diversity of avenues of investigation, which is facilitated by the regular arrangement of distinct neuronal populations and afferent fibre pathways, particularly in the hippocampus. NEW METHOD AND RESULTS: We have been interested in the regulation of seizure activity in hippocampal and neocortical slices by the purines, adenosine and ATP. Via the use of microelectrode biosensors we have been able to measure the release of these important neuroactive compounds simultaneously with on-going epileptiform activity, even of brief durations. In addition, detailed numerical analysis and computational modelling has produced new insights into the kinetics and spatial distribution of elevations in purine concentration that occur during seizure activity. COMPARISON AND CONCLUSIONS: Such an approach allows the spatio-temporal characteristics of neurotransmitter/neuromodulator release to be directly correlated with electrophysiological measures of synaptic and seizure activity, and can provide greater insight into the role of purines in epilepsy. PMID- 26381062 TI - Hydrolytic Transformation of Microporous Metal-Organic Frameworks to Hierarchical Micro- and Mesoporous MOFs. AB - A new approach to the synthesis of hierarchical micro- and mesoporous MOFs from microporous MOFs involves a simple hydrolytic post-synthetic procedure. As a proof of concept, a new microporous MOF, POST-66(Y), was synthesized and its transformation into a hierarchical micro- and mesoporous MOF by water treatment was studied. This method produced mesopores in the range of 3 to 20 nm in the MOF while maintaining the original microporous structure, at least in part. The degree of micro- and mesoporosity can be controlled by adjusting the time and temperature of hydrolysis. The resulting hierarchical porous MOF, POST-66(Y)-wt, can be utilized to encapsulate nanometer-sized guests such as proteins, and the enhanced stability and recyclability of an encapsulated enzyme is demonstrated. PMID- 26381064 TI - [Twelve hour work shifts, an opportunity?]. PMID- 26381063 TI - Synthesis, in vitro biological activities and in silico study of dihydropyrimidines derivatives. AB - We describe here the synthesis of dihydropyrimidines derivatives 3a-p, and evaluation of their alpha-glucosidase enzyme inhibition activities. Compounds 3b (IC50=62.4+/-1.5 MUM), 3c (IC50=25.3+/-1.26 MUM), 3d (IC50=12.4+/-0.15 MUM), 3e (IC50=22.9+/-0.25 MUM), 3g (IC50=23.8+/-0.17 MUM), 3h (IC50=163.3+/-5.1 MUM), 3i (IC50=30.6+/-0.6 MUM), 3m (IC50=26.4+/-0.34 MUM), and 3o (IC50=136.1+/-6.63 MUM) were found to be potent alpha-glucosidase inhibitors in comparison to the standard drug acarbose (IC50=840+/-1.73 MUM). The compounds were also evaluated for their in vitro cytotoxic activity against PC-3, HeLa, and MCF-3 cancer cell lines, and 3T3 mouse fibroblast cell line. All compounds were found to be non cytotoxic, except compounds 3f and 3m (IC50=17.79+/-0.66-20.44+/-0.30 MUM), which showed a weak cytotoxic activity against the HeLa, and 3T3 cell lines. In molecular docking simulation study, all the compounds were docked into the active site of the predicted homology model of alpha-glucosidase enzyme. From the docking result, it was observed that most of the synthesized compounds showed interaction through carbonyl oxygen atom and polar phenyl ring with active site residues of the enzyme. PMID- 26381065 TI - [Adolescence and distress. The body is severely tested]. PMID- 26381066 TI - [Obesity in adolescents: simple to diagnose, complex to treat]. AB - Obesity concerns 3 to 4% of adolescents between the ages of 11-18. It comes with multiple difficulties. On an immediate level, psychological suffering, the cause and consequence of a social malaise, favours the worsening of the obesity. To a lesser extent, somatic complications are either silent, or associated with a functional impact. Treatment is multi-disciplinary. PMID- 26381067 TI - [Anorexia, treating and caring for the mistreated body]. AB - Anorexia is a complex, multifactorial disease, emerging during puberty and requiring cross-disciplinary care. The body, taken hostage, expresses psychological suffering and the patient's developmental impasse. Compassionate treatment and the care given to this mistreated and undernourished body facilitate the access to the psychological care and are an essential step towards recovery. PMID- 26381068 TI - [Bulimia nervosa, a pathology with multiple complications]. AB - Bulimia nervosa is an eating disorder associating binge eating with inappropriate compensatory methods. Patients suffer from multiple organic, psychological and social complications. Of these, the somatic consequences are numerous and of varying degrees of seriousness. Regular monitoring is therefore essential in order to identify them and treat them. PMID- 26381069 TI - [Supporting a teenager confronted with a traumatic experience]. AB - Everyone reacts differently to a traumatic event. There is a risk of underestimating a teenager's traumatic experience by considering only the usual post-traumatic stress diagnosis criteria. However, when the trauma has not been able to be sufficiently developed, the adolescent's suffering is revealed through their behaviour. The therapeutic support of the youngster and their family enables them to reposition the traumatic event within the continuity of their history and to relaunch a thought process, often frozen by the traumatic experience. PMID- 26381071 TI - [Pediatric consultation receptionist, at the crossroads of two professions]. AB - As part of the reorganisation of a paediatric consultations department, the observation of the reception staff and its analysis opened up a discussion around the hospital's usual approach of separating administrative and nursing activities. Focusing on theoretical concepts of clinical analysis of work, the fonction of the reception staff was analysed in detail, revealing at the same time its invisible, often indescribable character. PMID- 26381070 TI - [The parents' experience of school refusal in adolescence]. AB - While today's society places considerable importance on schooling and performances, school absenteeism is currently very high. One of the causes is anxiety-based school refusal. This phenomenon affects the adolescent but also has an impact on their family. Exploring the experience of the parents of teenagers presenting anxiety-based school refusal enables these families to be given better support. PMID- 26381072 TI - [School inclusion of autistic children in adapted classes]. AB - A study was carried out into the subjective experience of the main people concerned by the schooling of autistic children in an inclusion classroom: the children, the parents and the teaching professionals. It highlights the need to take into account the transferential dimension of the pedagogical relationships. It also offers interesting perspectives with regard to clinical applications concerning the role of the school psychologist in supporting the professionals as well as the families. PMID- 26381073 TI - Stereotyped behaviours as precursors of self-injurious behaviours: a longitudinal study with infants and toddlers at risk for developmental delay. AB - BACKGROUND: The notion that stereotypic behaviours may be precursors of self injurious behaviour (SIB) has been considered in the past, but the available empirical evidence is still inconsistent and ambiguous. METHOD: In a longitudinal study, we collected data on stereotypic behaviour and SIB from 160 infants and toddlers who were at-risk for developmental delay. Interviews were conducted with parents at three time points during a one-year span using the Behaviour Problems Inventory-01 which contains subscales for SIB and stereotyped behaviour. We used growth modelling to estimate linear trends in several models. Model fit was evaluated according to a combination of fit statistics as is recommended in structural equation or latent variable modelling approaches such as latent growth modelling. RESULTS: In examining the relationship between stereotyped behaviours and SIB across time, the model that represented earlier stereotyped behaviour as predicting later SIB fit the data better than the other models. CONCLUSIONS: The findings corroborate the notion that stereotyped behaviour can be a precursor of SIB. If replicated by other studies, it makes a case for considering early intervening with stereotyped behaviour as a SIB prevention strategy. PMID- 26381074 TI - Carrier density distribution in silicon nanowires investigated by scanning thermal microscopy and Kelvin probe force microscopy. AB - The use of scanning thermal microscopy (SThM) and Kelvin probe force microscopy (KPFM) to investigate silicon nanowires (SiNWs) is presented. SThM allows imaging of temperature distribution at the nanoscale, while KPFM images the potential distribution with AFM-related ultra-high spatial resolution. Both techniques are therefore suitable for imaging the resistance distribution. We show results of experimental examination of dual channel n-type SiNWs with channel width of 100 nm, while the channel was open and current was flowing through the SiNW. To investigate the carrier distribution in the SiNWs we performed SThM and KPFM scans. The SThM results showed non-symmetrical temperature distribution along the SiNWs with temperature maximum shifted towards the contact of higher potential. These results corresponded to those expressed by the distribution of potential gradient along the SiNWs, obtained using the KPFM method. Consequently, non uniform distribution of resistance was shown, being a result of non-uniform carrier density distribution in the structure and showing the pinch-off effect. Last but not least, the results were also compared with results of finite-element method modeling. PMID- 26381075 TI - A study of threshold switching of NbO2 using atom probe tomography and transmission electron microscopy. AB - Threshold switching is a phenomenon where the resistivity of an insulating material changes and the insulator exhibits metallic behavior. This could be explained by phase transformation in oxide materials; however, this behavior is also seen in amorphous insulators. In this study, through an ex-situ experiment using transmission electron microscopy (TEM), we proved that threshold switching of amorphous NbO2 accompanies local crystallization. The change in I-V characteristics after electroforming was examined by evaluating the concentration profile. Atom probe tomography (APT) combined with in-situ TEM probing technique was performed to understand the threshold switching in amorphous NbO2. The local crystallization in amorphous NbO2 was validated by the observed difference in time-of-flight (ToF) between amorphous and crystalline NbO2. We concluded that the slower ToF of amorphous NbO2 (a-NbO2) compared with crystalline NbO2 (c-NbO2) is due to the resistivity difference and trap-assisted recombination. PMID- 26381076 TI - A cost-comparison of midwife-led compared with consultant-led maternity care in Ireland (the MidU study). AB - OBJECTIVE: to compare the cost of maternity care between two midwife-led units, and their linked consultant-led units, following a large randomised trial in Ireland. DESIGN: ethical approval was received for this unblinded, pragmatic randomised trial (MidU) funded by the Health Service Executive (Dublin North East, Ireland), conducted 2004-2009. A comparison of costs analysis was conducted on the outcomes from the trial. SETTING: two maternity units in Ireland, with 'alongside' midwife-led units. PARTICIPANTS: all women without risk factors for labour and birth who booked at the two maternity units before 24 weeks' gestation were assessed for inclusion. Consenting women (n=1653) were centrally randomised on a 2:1 ratio (1101:552) to midwife-led or consultant-led care. INTERVENTIONS: women randomised to consultant-led care received standard care. Women randomised to the midwife-led arm received midwife-led care provided by a small group of midwives in two units, situated 'alongside' the consultant-led units, throughout pregnancy, birth and postnatal. MEASUREMENTS: mean difference in clinician salaries, cost of care based on managers' data, known costs of postnatal bed days and costs of key interventions were measured. FINDINGS: the average cost of caring for a woman allocated to the midwife-led units was ?2598, compared to ?2780 in the consultant-led units (average difference ?182 per woman, analysed by 'intention to treat'). KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: care in these two midwife-led units costs less than care provided by the consultant-led units. Given the clinical findings, which showed that care provided in the midwife-led units is as safe as that in the consultant-led units and results in less intervention, more midwife-led units should be incorporated into maternity care in Ireland so that scarce resources can be used more effectively. PMID- 26381077 TI - Respiratory muscle training (RMT) in late-onset Pompe disease (LOPD): Effects of training and detraining. AB - BACKGROUND: Determine the effects of a 12-week respiratory muscle training (RMT) program in late-onset Pompe disease (LOPD). METHODS: We investigated the effects of 12-weeks of RMT followed by 3-months detraining using a single-subject A-B-A experimental design replicated across 8 adults with LOPD. To assess maximal volitional respiratory strength, our primary outcomes were maximum inspiratory pressure (MIP) and maximum expiratory pressure (MEP). Effect sizes for changes in MIP and MEP were determined using Cohen's d statistic. Exploratory outcomes targeted motor function, and peak cough flow (PCF) was measured in the last 5 subjects. RESULTS: From pretest to posttest, all 8 subjects exhibited increases in MIP, and 7 of 8 showed increases in MEP. Effect size data reveal the magnitude of increases in MIP to be large in 4 (d>=1.0) and very large in 4 (d>=2.0), and effect sizes for increases in MEP were large in 1 (d>=1.0) and very large in 6 (d>=2.0). Across participants, pretest to posttest MIP and MEP increased by a mean of 19.6% (sd=9.9) and 16.1% (sd=17.3), respectively. Respiratory strength increases, particularly for the inspiratory muscles, were generally durable to 3 months detraining. CONCLUSIONS: These data suggest our 12-week RMT program results in large to very large increases in inspiratory and expiratory muscle strength in adults with LOPD. Additionally, increases in respiratory strength appeared to be relatively durable following 3-months detraining. Although additional research is needed, RMT appears to offer promise as an adjunctive treatment for respiratory weakness in LOPD. PMID- 26381078 TI - Rapidly growing massive pleomorphic rhabdomyosarcoma of the bladder presenting with bladder outlet obstruction. PMID- 26381079 TI - Adolescent spinal pain: The pediatric orthopedist's point of view. AB - INTRODUCTION: Ten to twenty percent of persons experience spinal pain during growth. Causes are diverse in adolescents, and it is essential to determine etiology rapidly so as to guide optimal management. HYPOTHESIS: It is important for the pediatric orthopedist to understand the natural history of conditions inducing spinal pain. MATERIAL AND METHODS: A retrospective study included 116 adolescents presenting with spinal pain at the Hopital Nord (Marseille, France) between January 1, 2009 and January 1, 2014. Malignant tumoral etiologies were excluded. Mean patient age was 13.6 years. Risser ranged between >0 and <5. Interview and clinical examination (skin, spine, neurologic examination, general clinical examination) were systematic; depending on results, complementary examinations (imaging, biology, biopsy) were prescribed. RESULTS: There were 32 cases of non-specific adolescent low back pain, 31 of lumbar or thoracolumbar scoliosis, 23 of spinal growth dystrophy (Scheuermann's disease), 13 of isthmic lysis, 5 of spondylolisthesis, 8 of transitional lumbosacral hinge abnormality, 2 of discal hernia, 1 of osteoid osteoma and 1 of eosinophil granuloma. Treatment was often non-operative when diagnosis was sufficiently early. In case of failure, surgery could generally be considered. DISCUSSION: Correctly indicated non-operative management or surgery changes the natural history of these pathologies. The aim of treatment is to resolve pain in adolescence, as it risks becoming chronic and disabling by adulthood. PMID- 26381080 TI - Mating activity and sperm penetration assay in prediction of the reproduction potential of domestic goose ganders in a harem system. AB - In a natural mating system, the sexual behavior of birds has an important role in fertility success. Non-competitive mating system provides special conditions to study gander-goose interactions. Behavioral and physiological data from a domestic geese breeding flock was used to determine interrelationships between mating activity (MA) parameters, sperm penetration assay (SPA), plasma testosterone (T) concentration, and fertility (F). Moreover, variation in the frequency of gander-goose interactions during the intensive breeding period and the diurnal rhythm (short day - 10L:14D) were evaluated. The 2-/3-year-old ganders (n=15) and 1-/3-year-old geese (1?:4?) were observed. On the basis of successful copulation (SCop), groups of ganders with low (33.3%), intermediate (40%), and high (26.7%) frequency were categorized. Frequency of SCop was greater in the morning than in the afternoon. For the entire breeding period, SPA results obtained for the low frequency group were less than for the intermediate group. Fertility success for ganders from both low and intermediate groups was similar. There was a lack of association between MA, plasma T concentration, and SPA results. However, SCop was positively correlated with fertility. It is recommended that SCop be considered as a prognostic parameter for monitoring of ganders' reproductive potential. It is recommended that the sexual behavior of ganders be evaluated before the 1200h of the day. The SCop with an average frequency of 0.4-0.8 times during the day light hours appears to be associated with fertility results that are satisfactory for geese husbandry. Additionally, the SPA may be considered for identification of ganders with poor reproductive potential to facilitate the decision of changes in harem social structure during the first half of the breeding season. PMID- 26381081 TI - Phenotypic and phylogenetic segregation of Alternaria infectoria from small spored Alternaria species isolated from wheat in Germany and Russia. AB - AIMS: To identify the taxonomic differences between phytopathogenic small-spored Alternaria strains isolated from wheat kernels in Germany and Russia by a polyphasic approach. METHODS AND RESULTS: Ninety-five Alternaria (A.) strains were characterized by their colony colour, their three-dimensional sporulation patterns, mycotoxin production and phylogenetic relationships based on sequence variation in translation elongation factor 1-alpha (TEF1-alpha). The examination of toxin profiles and the phylogenetic features via TEF1-alpha resulted in two distinct clusters, in each case containing Alternaria infectoria isolates (92 and 96% respectively) in the first and the Alternaria alternata, Alternaria arborescens and Alternaria tenuissima isolates (77 and 79% respectively) in the other combined cluster. The production of Alternariol, Altertoxin and Altenuene has not been reported previously in the A. infectoria species group. The isolates from Germany and Russia differ slightly in species composition and mycotoxin production capacity. CONCLUSIONS: We identified that the A. infectoria species group can be differentiated from the A. alternata, A. arborescens and A. tenuissima species group by colour, low mycotoxin production and by the sequence variation in TEF1-alpha gene. SIGNIFICANCE AND IMPACT OF THE STUDY: These results allow a reliable toxic risk assessment when detecting different Alternaria fungi on cereals. PMID- 26381082 TI - MSH2 role in BRCA1-driven tumorigenesis: A preliminary study in yeast and in human tumors from BRCA1-VUS carriers. AB - BRCA1 interacts with several proteins implicated in homologous and non homologous recombination and in mismatch repair. The aim of this study is to determine if MSH2, a well known partner of BRCA1 involved in DNA repair, may contribute to breast and ovarian cancer development and progression. To better understand the functional interaction between BRCA1 and MSH2, we studied the effect of the deletion of MSH2 gene on BRCA1-induced genome instability in yeast. Preliminary results in yeast indicated that MSH2 and BRCA1 may interact to modulate homologous recombination (HR). We also carried out a genetic and epigenetic profiling of MSH2 gene by mutational analysis and promoter methylation evaluation in 9 breast and 2 ovarian tumors from carriers of BRCA1 unknown significance variants (VUS). 2/2 ovarian and 2/9 breast tumors carried MSH2 somatic mutations possible pathogenics (4/11, 36%): a missense mutation in exon 3 (p.G162R), a duplication of exon 1 and a deletion of exon 2. In addition, two germline synonymous variants in exon 11 were identified. None of the tumors showed promoter methylation. In conclusion, a surprisingly high frequency of MSH2 gene mutations has been found in tumor tissues from BRCA1 VUS carrier patients. This result supports the indication deriving from the yeast model that BRCA1 driven tumorigenesis may be modulated by MSH2. PMID- 26381083 TI - Aerobic Exercise as a Warm-Up for Singing: Aerodynamic Changes. AB - OBJECTIVES: This study was designed to determine the impact of aerobic exercise on vocal warm-up. STUDY DESIGN: This is a cohort experimental study. METHODS: Sixteen graduate and six undergraduate students in an academic vocal performance program participated. They completed a 30-minute treadmill workout in their target aerobic heart range. Aerodynamic data during singing were acquired before and after the treadmill workout. In full voice, participants sang the first seven notes of the Star Spangled Banner on "pah," repeating the seventh note seven times, at 1.5 syllables/s after an inhalation. The key was determined by voice type, with the target note within the range of passaggio for men, and in head voice for women. RESULTS: Paired t tests were performed on the data from 17 singers who maintained or increased sound pressure level (SPL) after exercise. Significant pre- to post-exercise increases were found for mean SPL and mean airflow during voicing, although increased estimated subglottal pressure approached significance. These measures were essentially unchanged in individuals who decreased SPL after exercise. There was no significant difference in vocal efficiency after the aerobic exercise, primarily due to large standard deviations within the pre- and post-exercise conditions. CONCLUSIONS: Most participants demonstrated favorable aerodynamic changes during singing after aerobic exercise. It is possible that in certain situations, a general aerobic warm-up could set the stage for a less-demanding vocal-specific warm-up, especially for a high voice performing early in the morning. PMID- 26381084 TI - Toxic effects of n-3 polyunsaturated fatty acids in human lung A549 cells. AB - N-3 polyunsaturated fatty acids (PUFAs), particularly eicosapentaenoic acid (EPA, 20:5) and docosahexaenoic acid (DHA, 22:6) are crucial for the prevention of lung cancer. PUFAs may act through alteration of membrane fluidity and cell surface receptor functions; modulation of cyclooxygenase activity; and increased cellular oxidative stress, which may induce apoptosis and autophagy. Therefore the aim of the study was to investigate whether EPA and DHA (25-100 MUM) are able to reduce human lung cancer cell growth through oxidative stress influence on autophagy and apoptosis. It was found that both EPA and DHA in the concentration-dependent manner suppressed the cell viability, enhanced cell death, induced activation of caspase-3/7 and potentiated intracellular oxidative DNA and protein damage. In response to PUFAs intracellular autophagic vacuolization occurred and the observed effect was reverted when the autophagy inhibitor 3-methyladenine (3-MA) was applied. The inhibition of the autophagic process enhanced the cell viability, suppressed cell death, and decreased activation of caspase-3/7 indicating that EPA and DHA-induced autophagy amplified A549 apoptotic cell death. PMID- 26381085 TI - In vitro toxicity of carbon nanotubes, nano-graphite and carbon black, similar impacts of acid functionalization. AB - Carbon nanotubes (CNT) and nano-graphite (NG) are graphene-based nanomaterials which share exceptional physicochemical properties, but whose health impacts are unfortunately still not well understood. On the other hand, carbon black (CB) is a conventional and widely studied material. The comparison of these three carbon based nanomaterials is thus of great interest to improve our understanding of their toxicity. An acid functionalization was carried out on CNT, NG and CB so that, after a thorough characterization, their impacts on RAW 264.7 macrophages could be compared for a similar surface chemistry (15 to 120 MUg.mL(-1) nanomaterials, 90-min to 24-h contact). Functionalized nanomaterials triggered a weak cytotoxicity similar to the pristine nanomaterials. Acid functionalization increased the pro-inflammatory response except for CB which did not trigger any TNF-alpha production before or after functionalization, and seemed to strongly decrease the oxidative stress. The toxicological impact of acid functionalization appeared thus to follow a similar trend whatever the carbon-based nanomaterial. At equivalent dose expressed in surface and equivalent surface chemistry, the toxicological responses from murine macrophages to NG were higher than for CNT and CB. It seemed to correspond to the hypothesis of a platelet and fiber paradigm. PMID- 26381086 TI - Predictors of hospitalization for lower respiratory tract infection in children aged <2 years in the province of Quebec, Canada. AB - Young age, adverse environmental conditions and infectious agents are established risk factors of lower respiratory tract infection (LRTI), whereas pneumococcal conjugate vaccines may be protective. To explore their relative role as predictors of hospitalizations under the continental climate prevailing in the province of Quebec, Canada, an ecological study was performed. Records with a main diagnosis of LRTI in children born during 2007-2010 and observed up to their second-year anniversary were extracted from the provincial hospital administrative database. Respiratory virus surveillance data and statistics on ambient air temperature were obtained. Vaccine use in different birth cohorts was derived from the Quebec City Immunization Registry. Additive and multiplicative Poisson regression models were applied to estimate attributable fractions. Age, month of birth, ambient temperature, and respiratory syncytial virus (RSV), human metapneumovirus (hMPV) and influenza-positive test proportions were significant predictors of LRTI hospitalizations. No substantial differences were observed in cohorts exposed to the 7-valent or 10-valent pneumococcal conjugate vaccines. In the additive model, the fraction of hospitalizations explained by temperature variation was 37%, whereas RSV circulation explained 28%, hMPV 4% and influenza 1%. Complex interplay between biological, environmental and social mechanisms may explain the important role of ambient air temperature in predicting LRTI hospitalization risk in young children. PMID- 26381087 TI - Phage Selection of Bicyclic Peptide Ligands of the Notch1 Receptor. AB - Precise regulation of the Notch signaling pathway is crucial, as increases or deficiencies in signaling are associated with diseases, including a wide range of cancers. Recent studies have demonstrated that monoclonal antibodies that bind and stabilize the structure of the negative regulatory region (NRR) in the extracellular domain of the Notch receptor can inhibit Notch signaling. In this work, we posed the question whether bicyclic peptides, being around 100-fold smaller than antibodies, can also stabilize the NRR and inhibit Notch signaling. Bicyclic peptides that bind the NRR of human Notch1 were isolated from combinatorial libraries by phage display. Affinity maturation yielded ligands with dissociation constant (Kd ) values as low as 150 nM. The bicyclic peptides increased the melting temperature of the NRR by up to 8 degrees C, thus substantially stabilizing the protein structure, but they did not inhibit Notch signaling in cellular assays. Although Notch signaling could not be inhibited, this work demonstrates that phage-selected bicyclic peptides can stabilize proteins; this capacity of bicyclic peptides may be exploited for modulating the conformation of other disease targets. PMID- 26381088 TI - Lead in Chinese villager house dust: Geographical variation and influencing factors. AB - House dust has been recognized as an important contributor to Pb exposure of children. Here we conducted a comprehensive study to investigate geographical variation of Pb in Chinese villager house dust. The influences of outdoor soil Pb concentrations, dates of construction, house decoration materials, heating types, and site specific pollution on Pb concentrations in house dust were evaluated. The concentrations of Pb in 477 house dust samples collected from twenty eight areas throughout China varied from 12 to 2510 mg/kg, with a median concentration of 42 mg/kg. The median Pb concentrations in different geographical areas ranged from 16 (Zhangjiakou, Hebei) to 195 mg/kg (Loudi, Hunan). No correlations were found between the house dust Pb concentrations and the age of houses, as well as house decoration materials. Whereas outdoor soil, coal combustion, and site specific pollution may be potential Pb sources. Principal component analysis (PCA) confirmed that elemental compositions of the house dust were controlled by both anthropogenic and geogenic sources. Using scanning electron microscopy (SEM), the Pb bearing particles in the house dust were also studied. PMID- 26381089 TI - Investing in success: student experiences in a structured, decelerated preclinical medical school curriculum. AB - PURPOSE: Many students in the Michigan State University College of Human Medicine (CHM) are non-traditional with unique needs and experiences. To meet these needs, in 1988 CHM developed a structured Extended Curriculum Program (ECP), which allows students to take longer than 2 years to complete the preclinical curriculum. This work examined the reasons why students extended their programs, their perceptions of that experience, and the outcome with respect to satisfaction and success in their careers after graduation. METHODS: The analysis used data from the college database, follow-up surveys of residency directors and graduates, surveys of graduates who extended, and the AMA Physician Masterfile. RESULTS: Graduates who responded to the survey were evenly split between those who extended for academic reasons and those who extended for other reasons. Although feelings about extending were mixed at the time of extension, nearly all respondents agreed that extending was the right decision in the long run. Extended students continued to face academic challenges having lower basic science averages, lower USMLE Step 1 and 2 first attempt pass rates, and more instances of repeated clerkships compared to those who did not extend, however, most were able to secure a residency in the specialty they desired and had comparable career satisfaction ratings. CONCLUSIONS: The ECP allows some students to complete medical school who otherwise may not have been able to do so. This analysis has provided valuable information that was used to improve the program, allowing CHM to continue its mission of training a diverse set of students to be exemplary physicians. PMID- 26381090 TI - Compensatory T-type Ca2+ channel activity alters D2-autoreceptor responses of Substantia nigra dopamine neurons from Cav1.3 L-type Ca2+ channel KO mice. AB - The preferential degeneration of Substantia nigra dopamine midbrain neurons (SN DA) causes the motor-symptoms of Parkinson's disease (PD). Voltage-gated L-type calcium channels (LTCCs), especially the Cav1.3-subtype, generate an activity related oscillatory Ca(2+) burden in SN DA neurons, contributing to their degeneration and PD. While LTCC-blockers are already in clinical trials as PD therapy, age-dependent functional roles of Cav1.3 LTCCs in SN DA neurons remain unclear. Thus, we analysed juvenile and adult Cav1.3-deficient mice with electrophysiological and molecular techniques. To unmask compensatory effects, we compared Cav1.3 KO mice with pharmacological LTCC-inhibition. LTCC-function was not necessary for SN DA pacemaker-activity at either age, but rather contributed to their pacemaker-precision. Moreover, juvenile Cav1.3 KO but not WT mice displayed adult wildtype-like, sensitised inhibitory dopamine-D2-autoreceptor (D2 AR) responses that depended upon both, interaction of the neuronal calcium sensor NCS-1 with D2-ARs, and on voltage-gated T-type calcium channel (TTCC) activity. This functional KO-phenotype was accompanied by cell-specific up-regulation of NCS-1 and Cav3.1-TTCC mRNA. Furthermore, in wildtype we identified an age dependent switch of TTCC-function from contributing to SN DA pacemaker-precision in juveniles to pacemaker-frequency in adults. This novel interplay of Cav1.3 L type and Cav3.1 T-type channels, and their modulation of SN DA activity-pattern and D2-AR-sensitisation, provide new insights into flexible age- and calcium dependent activity-control of SN DA neurons and its pharmacological modulation. PMID- 26381091 TI - 'Obesity' is healthy for cetaceans? Evidence from pervasive positive selection in genes related to triacylglycerol metabolism. AB - Cetaceans are a group of secondarily adapted marine mammals with an enigmatic history of transition from terrestrial to fully aquatic habitat and subsequent adaptive radiation in waters around the world. Numerous physiological and morphological cetacean characteristics have been acquired in response to this drastic habitat transition; for example, the thickened blubber is one of the most striking changes that increases their buoyancy, supports locomotion, and provides thermal insulation. However, the genetic basis underlying the blubber thickening in cetaceans remains poorly explored. Here, 88 candidate genes associated with triacylglycerol metabolism were investigated in representative cetaceans and other mammals to test whether the thickened blubber matched adaptive evolution of triacylglycerol metabolism-related genes. Positive selection was detected in 41 of the 88 candidate genes, and functional characterization of these genes indicated that these are involved mainly in triacylglycerol synthesis and lipolysis processes. In addition, some essential regulatory genes underwent significant positive selection in cetacean-specific lineages, whereas no selection signal was detected in the counterpart terrestrial mammals. The extensive occurrence of positive selection in triacylglycerol metabolism-related genes is suggestive of their essential role in secondary adaptation to an aquatic life, and further implying that 'obesity' might be an indicator of good health for cetaceans. PMID- 26381092 TI - Discovery of small molecule inhibitors of MyD88-dependent signaling pathways using a computational screen. AB - In this study, we used high-throughput computational screening to discover drug like inhibitors of the host MyD88 protein-protein signaling interaction implicated in the potentially lethal immune response associated with Staphylococcal enterotoxins. We built a protein-protein dimeric docking model of the Toll-interleukin receptor (TIR)-domain of MyD88 and identified a binding site for docking small molecules. Computational screening of 5 million drug-like compounds led to testing of 30 small molecules; one of these molecules inhibits the TIR-TIR domain interaction and attenuates pro-inflammatory cytokine production in human primary cell cultures. Compounds chemically similar to this hit from the PubChem database were observed to be more potent with improved drug like properties. Most of these 2(nd) generation compounds inhibit Staphylococcal enterotoxin B (SEB)-induced TNF-alpha, IFN-gamma, IL-6, and IL-1beta production at 2-10 MUM in human primary cells. Biochemical analysis and a cell-based reporter assay revealed that the most promising compound, T6167923, disrupts MyD88 homodimeric formation, which is critical for its signaling function. Furthermore, we observed that administration of a single dose of T6167923 completely protects mice from lethal SEB-induced toxic shock. In summary, our in silico approach has identified anti-inflammatory inhibitors against in vitro and in vivo toxin exposure with promise to treat other MyD88-related pro-inflammatory diseases. PMID- 26381093 TI - In vivo confocal microscopy of early corneal epithelial recovery in patients with chemical injury. AB - PURPOSE: To investigate the early recovery of corneal epithelium in patients with chemical injuries by the application of in vivo laser scanning confocal microscopy (LSCM). METHODS: LSCM was performed on 26 eyes of 18 consecutive patients at 1, 2, and 3 months post injury. The morphology of central corneal epithelium and limbus was evaluated. Analysis was performed to compare the densities of corneal apical surface cells (ASCs) and basal epithelial cells (BECs) among different injury severity and time points after injury. The comparisons were also made on inflammatory cells (ICs) and dendritic cells (DCs) infiltrating at the limbus. Moreover, the presence rate of palisades of Vogt (POV) was analyzed at 3 months post injury. RESULTS: Corneal re-epithelialization was found within 3 months post injury in all eyes, except that persistent epithelium defect was identified in grade IV injured eyes even at 3 months after injury. The injury severity had a significantly negative correlation with the densities of ASCs. However, it had no relationship with the densities of BECs. The density of ICs at the limbus decreased significantly with the prolongation of follow-up, except in the grade I injured eyes. The presence rate of POV also had a significantly negative correlation with injury severity. CONCLUSION: Epithelial recovery after chemical injury varied in cellular morphology and the densities of ASCs among eyes with different injury severity. The presence rates of POV decreased with the aggravation of injury. LSCM is a feasible method for observing the early recovery of corneal epithelium in patients with chemical injuries. PMID- 26381094 TI - Optical coherence tomographic angiography shows reduced deep capillary flow in paracentral acute middle maculopathy. AB - INTRODUCTION: Paracentral acute middle maculopathy (PAMM) has been described as an ischemic lesion of the middle retinal layers with a characteristic lamellar hyper-reflective placoid appearance in the acute phase and thinning of the involved retinal layers in the chronic phase. Optical coherence tomographic angiography (OCTA) is a novel and non-invasive technique for imaging retinal capillary vasculature with en face segmentation capabilities. METHOD: Case series. We describe two patients with PAMM who underwent clinical examination and multimodal imaging including OCTA. RESULTS: In the first patient, who presented with PAMM secondary to acute cilioretinal artery occlusion, OCTA demonstrated reduction in flow in the deep capillary plexus (DCP). One month later, OCTA revealed a flow void due to thinning of the GCL, INL, and OPL and paradoxical apparent ONL thickening. Similar findings of focal retinal lamellar ectopia were seen in the second patient, who had an incidentally detected chronic PAMM lesion. CONCLUSIONS: OCTA images the superficial and deep capillary plexi independently. PAMM is characterized by acute and chronic attenuation of the DCP flow signature. Focal lamellar ectopia in PAMM is discussed. PMID- 26381095 TI - Comment on 'Failure of intravitreal bevacizumab in the treatment of choroidal metastasis'. PMID- 26381096 TI - Intravitreal bevacizumab for choroidal metastases: the key to efficacy is simultaneous administration of systemic therapy. PMID- 26381097 TI - Incidence and risk factors for traumatic intraocular pressure elevation and traumatic glaucoma after open-globe injury. AB - PURPOSE: To examine traumatic intraocular pressure (IOP) elevation and glaucoma after open-globe injury. DESIGN: Retrospective, observational case series. METHODS: Review of patients with open-globe repair at the University of Washington from May 1997 through July 2010. Traumatic IOP elevation and glaucoma were defined respectively as intraocular pressure (IOP) >=22 mm Hg at >1 visit or need for glaucoma medication, and long-term (at least 3 months) glaucoma medication use or glaucoma surgery. RESULTS: We included 515 eyes (515 patients). The mean follow-up was 12.6+/-20.1 months. One hundred twenty eyes (23.3%) developed traumatic IOP elevation, of which 32 (6.2%) developed glaucoma; six eyes (1.2%) required glaucoma surgery. The mean time to development of traumatic IOP elevation was 1.5+/-3.4 months (range 1 day to 2 years). Kaplan-Meier 6- and 12-month estimates for development of traumatic IOP elevation were 27.2 and 32.4%, respectively, and for development of traumatic glaucoma were 7.1 and 11.0%, respectively. Multivariate regression revealed associations between traumatic IOP elevation and older age, and traumatic glaucoma and prior penetrating keratoplasty, initial vitreous hemorrhage, Zone II injury, and penetrating keratoplasty after open-globe repair. Traumatic glaucoma was controlled (IOP <22 mm Hg) in 78.1% of eyes at final follow-up, with mean IOP of 18.2 mm Hg on 1.7 medications. CONCLUSIONS: Traumatic IOP elevation and glaucoma were common after visually salvageable open-globe injury. Most cases developed within 6 months, although longer follow-up remains important for case detection. Penetrating keratoplasty before or after repair, and vitreous hemorrhage were notable risk factors. PMID- 26381099 TI - Understanding the patient's lived experience of neovascular age-related macular degeneration: a qualitative study. AB - PURPOSE: In industrialised populations age-related macular degeneration (ARMD) is the leading cause of visual disability of the elderly. Successful new treatment with anti-endothelial growth factors for neovascular-classified ARMD has led to a divergence in treatment and experiences of people ARMD. This study aimed to understand the participant's experience of neovascular ARMD, including ongoing treatment with anti-vascular endothelial growth factor. METHODS: Twenty-five participants from one clinical site were qualitatively interviewed to elicit their experiences of treatment for neovascular ARMD. RESULTS: Two major themes were identified. A life negotiated by neovascular ARMD captures the participants' experience of living with the condition and treatment regime for neovascular ARMD. The second major theme: Uncertainty displayed their appraisal of life, treatment and their perceived future. CONCLUSIONS: Anxieties concerning the injections, new limitations to lifestyles, and an uncertain future all emerged from the data analysis. However, thankfulness for the treatment, the importance of familiar patterns in treatments and recovery and a guarded optimism also emerged. Knowledge of the experiences, anxieties and concerns of this patient population can be used to inform clinical practice and lead to patient-centred care. PMID- 26381098 TI - Associations of FPG, A1C and disease duration with protein markers of oxidative damage and antioxidative defense in type 2 diabetes and diabetic retinopathy. AB - PURPOSE: To investigate the role of protein oxidative damage and antioxidant defense in relationship to hyperglycemia measured as fasting plasma glucose (FPG), glycated hemoglobin (A1C), and duration of disease in type 2 diabetes mellitus (DM) and diabetic retinopathy (DR). METHODS: This study recruited 23 non diabetic subjects, 16 DM patients without any complications and 18 DR patients. The serum ischemia modified albumin (IMA) and glutathione (GSH) levels were measured. The IMA results were corrected for serum albumin. Between-group differences were studied by analysis of variance and between-variable associations were studied by Spearman's and partial correlations. RESULTS: IMA and cIMA values were elevated, whereas GSH was decreased in both patient groups vs controls (P<0.05), and the increase in IMA formation is not related to serum albumin changes. DR patients have much severe oxidative stress (OS) status with high IMA and cIMA, and low GSH than in the DM group (P<0.05). Both FPG and A1C levels were positively associated with IMA in DM group, while in the DR group, duration of disease too had a positive association with IMA. The antioxidant GSH had negative correlations with FPG (r=-0.52, P=0.02) and IMA (r=-0.49, P=0.03) in the DR group. Partial correlation analyses predicted mutual or independent associations among parameters. CONCLUSIONS: Severe OS in DR has been associated with increased FPG, A1C, and disease duration. Both hyperglycemia and elevated oxidative damage detected as IMA are collectively associated with depleted GSH status. Our study unravels the need for monitoring of OS in addition to standard glycemic management in DR. PMID- 26381100 TI - Horner's syndrome in patients admitted to the intensive care unit that have undergone central venous catheterization: a prospective study. AB - PurposeCentral venous catheterization (CVC) is estimated to be performed in millions of patients per year. Swan-Ganz catheters used for CVC are most often inserted into the internal jugular vein and during this procedure they may come into contact with the sympathetic chain. This study aims to determine the incidence of Horner's syndrome in patients admitted to intensive care unit that have undergone internal jugular CVC insertion during their admission and to determine whether ultrasonography-assisted insertion has decreased the frequency of this complication.Patients and methodsA total of 100 prospective patients admitted to the ICU were examined for the presence of anisocoria and ptosis after undergoing recent CVC. Presence of Horner's syndrome was confirmed by testing with 0.5% apraclonidine and looking for the reversal of anisocoria.ResultsFrequency of Horner's syndrome after CVC was 2% in a sample of 100 prospectively examined patients.ConclusionHorner's syndrome remains a relatively rare but definitive complication of CVC. ICU physicians should be educated about its existence and prevalence and ophthalmologists should inquire about any history of ICU admission necessitating CVC insertion in any patient presenting with Horner's syndrome. PMID- 26381101 TI - Ultrafast multidimensional Laplace NMR for a rapid and sensitive chemical analysis. AB - Traditional nuclear magnetic resonance (NMR) spectroscopy relies on the versatile chemical information conveyed by spectra. To complement conventional NMR, Laplace NMR explores diffusion and relaxation phenomena to reveal details on molecular motions. Under a broad concept of ultrafast multidimensional Laplace NMR, here we introduce an ultrafast diffusion-relaxation correlation experiment enhancing the resolution and information content of corresponding 1D experiments as well as reducing the experiment time by one to two orders of magnitude or more as compared with its conventional 2D counterpart. We demonstrate that the method allows one to distinguish identical molecules in different physical environments and provides chemical resolution missing in NMR spectra. Although the sensitivity of the new method is reduced due to spatial encoding, the single-scan approach enables one to use hyperpolarized substances to boost the sensitivity by several orders of magnitude, significantly enhancing the overall sensitivity of multidimensional Laplace NMR. PMID- 26381102 TI - Brief Report: Increasing Acceptance of Homosexuality in the United States Across Racial and Ethnic Subgroups. AB - After recent civil rights expansions for sexual minorities in the United States, we updated previous findings on population-level attitudes toward homosexuality measured in the General Social Survey. In 2014, 40.1% of respondents reported that homosexuality was "always wrong" compared with 54.8% in 2008 (P < 0.001). Although black and Hispanic respondents consistently reported more negative attitudes regarding homosexuality than white respondents throughout 2008 to 2014, the percentage declined among all racial/ethnic groups. Among MSM, more positive attitudes were associated with HIV testing. Research shows a potential association between homophobia and HIV risk; thus, these population-level changes may promote better health among MSM. PMID- 26381103 TI - Genetic Sequencing Analysis of A307 Subgroup of ABO Blood Group. AB - BACKGROUND The aim of this study was to investigate the serology and gene sequence characteristics of the A307 subgroup of the ABO blood group. MATERIAL AND METHODS Monoclonal anti-A and anti-B antibodies were used to detect the ABO antigens of a proband whose positive blood type was not consistent with the negative blood type of the ABO blood group. Standard A-, B-, and O-negative typing cells were used to test for ABO antibodies in the serum. Additionally, polymerase chain reaction with sequence-specific primer (PCR-SSP) was used to confirm the genotype, and subsequently, exons 6 and 7 of the ABO gene were detected by gene sequencing. Samples from the wife and daughters of the proband were also used for serological and genetic testing. RESULTS Red blood cells of the proband showed weak agglutination reaction with anti-A antibody, while anti-B antibody was detected in the serum. Moreover, PCR-SSP detected A307 and O02 alleles, while gene sequencing revealed mutation of c.745C>T in exon 7, which produced a polypeptide chain p.R249W. The A307 gene of the proband was not inherited by his daughters. CONCLUSIONS A mutation (c.745 C>T) in exon 7 of the ABO blood group gene resulted in low activity of a-1,3-N-acetyl-galactosaminyl transferase, producing A3 phenotype. PMID- 26381104 TI - Home Telehealth Video Conferencing: Perceptions and Performance. AB - BACKGROUND: The Flinders Telehealth in the Home trial (FTH trial), conducted in South Australia, was an action research initiative to test and evaluate the inclusion of telehealth services and broadband access technologies for palliative care patients living in the community and home-based rehabilitation services for the elderly at home. Telehealth services at home were supported by video conferencing between a therapist, nurse or doctor, and a patient using the iPad tablet. OBJECTIVE: The aims of this study are to identify which technical factors influence the quality of video conferencing in the home setting and to assess the impact of these factors on the clinical perceptions and acceptance of video conferencing for health care delivery into the home. Finally, we aim to identify any relationships between technical factors and clinical acceptance of this technology. METHODS: An action research process developed several quantitative and qualitative procedures during the FTH trial to investigate technology performance and users perceptions of the technology including measurements of signal power, data transmission throughput, objective assessment of user perceptions of videoconference quality, and questionnaires administered to clinical users. RESULTS: The effectiveness of telehealth was judged by clinicians as equivalent to or better than a home visit on 192 (71.6%, 192/268) occasions, and clinicians rated the experience of conducting a telehealth session compared with a home visit as equivalent or better in 90.3% (489/540) of the sessions. It was found that the quality of video conferencing when using a third generation mobile data service (3G) in comparison to broadband fiber-based services was concerning as 23.5% (220/936) of the calls failed during the telehealth sessions. The experimental field tests indicated that video conferencing audio and video quality was worse when using mobile data services compared with fiber to the home services. As well, statistically significant associations were found between audio/video quality and patient comfort with the technology as well as the clinician ratings for effectiveness of telehealth. CONCLUSIONS: These results showed that the quality of video conferencing when using 3G-based mobile data services instead of broadband fiber-based services was less due to failed calls, audio/ video jitter, and video pixilation during the telehealth sessions. Nevertheless, clinicians felt able to deliver effective services to patients at home using 3G-based mobile data services. PMID- 26381105 TI - Density-functional calculations of the conversion of methane to methanol on platinum-decorated sheets of graphene oxide. AB - By means of calculations based on density-functional theory (DFT), we have investigated the conversion of methane on two platinum atoms supported with a graphene-oxide sheet (Pt2/GO). In our calculations, a CH4 molecule can be adsorbed around the Pt atoms of the Pt2/GO sheet with adsorption energies within 0.11 to -0.53 eV; an elongated C-H bond indicates that Pt atoms on that sheet can activate the C-H bond of a CH4 molecule. The role of the GO sheet in the activation of CH4 was identified according to an analysis of the electronic density: the GO sheet induces the d-band of Pt atoms to generate several specific dz(2) state features above the Fermi level, which enabled the activation of the C H bond of CH4 in generating an evident area of overlap with the hydrogen s orbital of the C-H bond. Upon a dioxygen molecule being added onto the Pt2/GO sheet, this molecule can react with activated CH4 according to mechanisms of form 2CH4 + O2 [Pt2/GO]--> 2CH3OH, and restore the original Pt2/GO sheet. PMID- 26381106 TI - Environmental potential of carbon dioxide utilization in the polyurethane supply chain. AB - Potential environmental benefits have been identified for the utilization of carbon dioxide (CO2) as a feedstock for polyurethanes (PUR). CO2 can be utilized in the PUR supply chain in a wide variety of ways ranging from direct CO2 utilization for polyols as a PUR precursor, to indirect CO2 utilization for basic chemicals in the PUR supply chain. In this paper, we present a systematic exploration and environmental evaluation of all direct and indirect CO2 utilization options for flexible and rigid PUR foams. The analysis is based on an LCA-based PUR supply chain optimization model using linear programming to identify PUR production with minimal environmental impacts. The direct utilization of CO2 for polyols allows for large specific impact reductions of up to 4 kg CO2-eq. and 2 kg oil-eq. per kg CO2 utilized, but the amounts of CO2 that can be utilized are limited to 0.30 kg CO2 per kg PUR. The amount of CO2 utilized can be increased to up to 1.7 kg CO2 per kg PUR by indirect CO2 utilization in the PUR supply chain. Indirect CO2 utilization requires hydrogen (H2). The environmental impacts of H2 production strongly affect the impact of indirect CO2 utilization in PUR. To achieve optimal environmental performance under the current fossil-based H2 generation, PUR production can only utilize much less CO2 than theoretically possible. Thus, utilizing as much CO2 in the PUR supply chain as possible is not always environmentally optimal. Clean H2 production is required to exploit the full CO2 utilization potential for environmental impact reduction in PUR production. PMID- 26381108 TI - Ruthenium Catalyzed Selective alpha- and alpha,beta-Deuteration of Alcohols Using D2O. AB - Highly selective ruthenium catalyzed alpha-deuteration of primary alcohols and alpha,beta-deuteration of secondary alcohols are achieved using deuterium oxide (D2O) as a source of deuterium and reaction solvent. Minimal loading of catalyst (Ru-macho), base (KO(t)Bu), and low temperature heating provided efficient selective deuteration of alcohols making the process practically attractive and environmentally benign. Mechanistic studies indicate the D-O(D/R) bond activations by metal-ligand cooperation and intermediacy of carbonyl compounds resulting from dehydrogenation of alcohols. PMID- 26381107 TI - A latent reactive handle for functionalising heparin-like and LMWH deca- and dodecasaccharides. AB - d-Glucosamine derivatives bearing latent O4 functionality provide modified H/HS type disaccharide donors for a final stage capping approach enabling introduction of conjugation-suitable, non-reducing terminal functionality to biologically important glycosaminoglycan oligosaccharides. Application to the synthesis of the first O4-terminus modified synthetic LMWH decasaccharide and an HS-like dodecasaccharide is reported. PMID- 26381109 TI - Double Detection of Mycotoxins Based on SERS Labels Embedded Ag@Au Core-Shell Nanoparticles. AB - A sensitive surface-enhanced Raman scattering (SERS) signal dependent double detection of mycotoxins is achieved for the first time, without the aid of nucleic acid amplification strategies. SERS labels embedded Ag@Au core-shell (CS) nanoparticles (NPs) as novel SERS tags are successfully prepared through a galvanic replacement-free deposition. SERS tags produce stable and quantitative SERS signal, emerging from the plasmonic coupling at the junction of Ag core and Au shell. SERS tags engineered Raman aptasensors are developed for the double detection of ochratoxin A (OTA) and aflatoxin B1 (AFB1) in maize meal. The limits of detection (LODs) are as low as 0.006 ng/mL for OTA and 0.03 ng/mL for AFB1. The developed protocol can be extended to a large set of different SERS tags for the sensitive detection of multiple targets that possess different lengths of aptamers. PMID- 26381110 TI - How Does Poly(hydroxyalkanoate) Affect Methane Production from the Anaerobic Digestion of Waste-Activated Sludge? AB - Recent studies demonstrate that, besides being used for production of biodegradable plastics, poly(hydroxyalkanoate) (PHA) that is accumulated in heterotrophic microorganisms during wastewater treatment has another novel application direction, i.e., being utilized for enhancing methane yield during the anaerobic digestion of waste-activated sludge (WAS). To date, however, the underlying mechanism of how PHA affects methane production remains largely unknown, and this limits optimization and application of the strategy. This study therefore aims to fill this knowledge gap. Experimental results showed that with the increase of sludge PHA levels from 21 to 184 mg/g of volatile suspended solids (VSS) the methane yield linearly increased from 168.0 to 246.1 mL/g of VSS (R(2) = 0.9834). Compared with protein and carbohydrate (the main components of a cell), PHA exhibited a higher biochemical methane potential on a unit VSS basis. It was also found that the increased PHA not only enhanced cell disruption of PHA cells but also benefited the soluble protein conversion of both PHA- and non-PHA cells. Moreover, the reactor fed with higher PHA sludge showed greater sludge hydrolysis and acidification than those fed with the lower PHA sludges. Further investigations using fluorescence in situ hybridization and enzyme analysis revealed that the increased PHA enhanced the abundance of methanogenic Archaea and increased the activities of protease, acetate kinase, and coenzyme F420, which were consistent with the observed methane yield. This work provides insights into PHA-involved WAS digestion systems and may have important implications for future operation of wastewater treatment plants. PMID- 26381111 TI - Counting the Isomers and Estimation of Anisotropy of Polarizability of the Selected C60 and C70 Bisadducts Promising for Organic Solar Cells. AB - Currently, bisadducts of C60 and C70 fullerenes are widely studied as electron acceptor materials for organic solar cells. These compounds are usually used as mixtures of the positional isomers. However, as recently shown, the separate use of the purified isomers with lowest anisotropies of polarizability may enhance solar cell output parameters. To predict the structures of the compounds appropriate for this purpose, we calculated anisotropies of polarizability of four classes of fullerene bisadducts, namely, bis-[60]PCBM, [60]OQMF, bis [70]PCBM, and [70]OQMF (18, 16, 41, and 42 positional isomers, respectively). As found, the anisotropies quadratically correlate with the interaddend distances in fullerene bisadducts, whereas there are no obvious correlations between the structures and lowest unoccupied molecular orbital levels, traditionally used for assessing the efficiency of candidates for organic solar cell electron acceptors. According to our calculations, bisadducts bis-[60]PCBM-ee-1, [60]OQMF-cis-3.2, [60]OQMF-trans-4.2, cc(1.1)cc(2'.1)-bis-[70]PCBM, and cc1cc(2'.1)-[70]OQMF have the lowest anisotropies of polarizability. These compounds have a primary interest for synthesis, purification, and further separate testing in solar cells. The structures of these adducts have a common feature, which we describe with the "not so close and not so far" rule: the distances between the addends in the most isotropic fullerene bisaddicts should be medium among the possible values. These are ee, ef, cis-3, and trans-4 positions in the case of the C60 bisadducts and cc bonds placed on the different poles and the same hemisphere of the C70 skeleton. PMID- 26381112 TI - Insights into Solid-State Electron Transport through Proteins from Inelastic Tunneling Spectroscopy: The Case of Azurin. AB - Surprisingly efficient solid-state electron transport has recently been demonstrated through "dry" proteins (with only structural, tightly bound H2O left), suggesting proteins as promising candidates for molecular (bio)electronics. Using inelastic electron tunneling spectroscopy (IETS), we explored electron-phonon interaction in metal/protein/metal junctions, to help understand solid-state electronic transport across the redox protein azurin. To that end an oriented azurin monolayer on Au is contacted by soft Au electrodes. Characteristic vibrational modes of amide and amino acid side groups as well as of the azurin-electrode contact were observed, revealing the azurin native conformation in the junction and the critical role of side groups in the charge transport. The lack of abrupt changes in the conductance and the line shape of IETS point to far off-resonance tunneling as the dominant transport mechanism across azurin, in line with previously reported (and herein confirmed) azurin junctions. The inelastic current and hence electron-phonon interaction appear to be rather weak and comparable in magnitude with the inelastic fraction of tunneling current via alkyl chains, which may reflect the known structural rigidity of azurin. PMID- 26381113 TI - Combined Squamomelanocytic Tumor of the Plantar Surface of the Foot: Histogenetic Insights. PMID- 26381114 TI - The Challenge of Diagnosing Mycosis Fungoides. PMID- 26381115 TI - Milia En Plaque as a Distinct Follicular Hamartoma With Cystic Trichoepitheliomatous Features. AB - Milia en plaque (MEP) is an uncommon disorder characterized by an erythematous plaque containing numerous milia. The pathogenesis of MEP is not clear. The authors report a man with an erythematous plaque on the right retroauricular area, containing numerous white-yellow cysts varying in size. Histological examination showed that multiple cystic structures at various levels of the dermis that were lined by stratified squamous epithelium and contained keratinous material-these findings were consistent with the diagnosis of multiple milia. In addition to epidermal cysts, however, the lesion consisted of a branched proliferation of pale-staining keratinocytes lined with basal keratinocytes budding from the overlying epidermis. Moreover, some cysts were formed within the branched epithelial proliferation, had thicker cyst walls than the ordinary milium, or had irregular or branched projections toward the surrounding dermis. From these findings, the authors conclude that MEP is a distinct follicular hamartoma with cystic trichoepitheliomatous features. PMID- 26381116 TI - Expression of Malic Enzymes in Sebaceous Lesions. AB - Malic enzymes (MEs) are involved in fatty acid biosynthesis and lipid accumulation, and their expression in sebocytes and sebaceous lesions has not been investigated. The aims of this study were to examine ME1 and ME2 expression in normal skin and sebaceous lesions. A total of 68 cases including 5 specimens of normal skin, 12 facial lesions showing sebaceous hyperplasia, 18 sebaceous adenomas, 10 sebaceomas, 13 steatocystomas, and 10 sebaceous carcinomas were examined for the expression of ME1 and ME2. All benign and malignant sebaceous lesions showed ME1 in clear cells and ME2 in nonclear cells, respectively. ME1/ME2 phenotype is seen in basal sebocytes, basal keratinocytes, sweat glands, and outer root sheath cells and hence not specific. This study demonstrates that ME1/ME2 expression phenotype may have a potential to be a valuable marker for sebaceous differentiation. It is necessary to perform large-scale studies including skin tumors with a clear cell morphology that may mimic sebaceous differentiation. PMID- 26381118 TI - Effects of different rapid maxillary expansion appliances on facial soft tissues using three-dimensional imaging. AB - OBJECTIVE: To determine three-dimensional (3D) effects of three different rapid maxillary expansion (RME) appliances on facial soft tissues. MATERIALS AND METHODS: Forty-two children (18 boys, 24 girls) who required RME treatment were included in this study. Patients were randomly divided into three equal groups: banded RME, acrylic splint RME, and modified acrylic splint RME. For each patient, 3D images were obtained before treatment (T1) and at the end of the 3 month retention (T2) with the 3dMD system. RESULTS: When three RME appliances were compared in terms of the effects on the facial soft tissues, there were no significant differences among them. The mouth and nasal width showed a significant increase in all groups. Although the effect of the acrylic splint RME appliances on total face height was less than that of the banded RME, there was no significant difference between the appliances. The effect of the modified acrylic splint appliance on the upper lip was significant according to the volumetric measurements (P < .01). CONCLUSIONS: There were no significant differences among three RME appliances on the facial soft tissues. The modified acrylic splint RME produced a more protrusive effect on the upper lip. PMID- 26381119 TI - Variability and Diagnostic Accuracy of Speech Intelligibility Scores in Children. AB - PURPOSE: We examined variability of speech intelligibility scores and how well intelligibility scores predicted group membership among 5-year-old children with speech motor impairment (SMI) secondary to cerebral palsy and an age-matched group of typically developing (TD) children. METHOD: Speech samples varying in length from 1-4 words were elicited from 24 children with cerebral palsy (mean age 60.50 months) and 20 TD children (mean age 60.33 months). Two hundred twenty adult listeners made orthographic transcriptions of speech samples (n = 5 per child). RESULTS: Variability associated with listeners made a significant contribution to explaining the variance in intelligibility scores for TD and SMI children, but the magnitude was greater for TD children. Intelligibility scores differentiated very well between children who have SMI and TD children when intelligibility was at or below approximately 75% and above approximately 85%. CONCLUSIONS: Intelligibility seems to be a useful clinical tool for differentiating between TD children and children with SMI at 5 years of age; however, there is considerable variability within and between listeners, highlighting the need for more than one listener per child to ensure validity of an intelligibility measure. PMID- 26381120 TI - Family planning use and fertility desires among women living with HIV in Kenya. AB - BACKGROUND: Enabling women living with HIV to effectively plan whether and when to become pregnant is an essential right; effective prevention of unintended pregnancies is also critical to reduce maternal morbidity and mortality as well as vertical transmission of HIV. The objective of this study is to examine the use of family planning (FP) services by HIV-positive and HIV-negative women in Kenya and their ability to achieve their fertility desires. METHODS: Data are derived from a random sample of women seeking family planning services in public health facilities in Kenya who had declared their HIV status (1887 at baseline and 1224 at endline) and who participated in a longitudinal study (the INTEGRA Initiative) that measured the benefits/costs of integrating HIV and sexual/reproductive health services in public health facilities. The dependent variables were FP use in the last 12 months and fertility desires (whether a woman wants more children or not). The key independent variable was HIV status (positive and negative). Descriptive statistics and multivariate logistic regression analysis were used to describe the women's characteristics and to examine the relationship between FP use, fertility desires and HIV status. RESULTS: At baseline, 13 % of the women sampled were HIV-positive. A slightly higher proportion of HIV-positive women were significantly associated with the use of FP in the last 12 months and dual use of FP compared to HIV-negative women. Regardless of HIV status, short-acting contraceptives were the most commonly used FP methods. A higher proportion of HIV-positive women were more likely to be associated with unintended (both mistimed and unwanted) pregnancies and a desire not to have more children. After adjusting for confounding factors, the multivariate results showed that HIV-positive women were significantly more likely to be associated with dual use of FP (OR = 3.2; p < 0.05). Type of health facility, marital status and household wealth status were factors associated with FP use. Factors associated with fertility desires were age, education level and household wealth status. CONCLUSIONS: The findings highlight important gaps related to utilization of FP among WLHIV. Despite having a greater likelihood of reported use of FP, HIV-positive women were more likely to have had an unintended pregnancy compared to HIV-negative women. This calls for need to strengthen family planning services for WLHIV to ensure they have better access to a wide range of FP methods. There is need to encourage the use of long-acting reversible contraceptive (LARC) to reduce the risk of unintended pregnancy and prevention of vertical transmission of HIV. However, such policies should be based on respect for women's right to informed reproductive choice in the context of HIV/AIDS. TRIAL REGISTRATION: NCT01694862. PMID- 26381121 TI - Phosphoproteome dynamics mediate revival of bacterial spores. AB - BACKGROUND: Bacterial spores can remain dormant for decades, yet harbor the exceptional capacity to rapidly resume metabolic activity and recommence life. Although germinants and their corresponding receptors have been known for more than 30 years, the molecular events underlying this remarkable cellular transition from dormancy to full metabolic activity are only partially defined. RESULTS: Here, we examined whether protein phospho-modifications occur during germination, the first step of exiting dormancy, thereby facilitating spore revival. Utilizing Bacillus subtilis as a model organism, we performed phosphoproteomic analysis to define the Ser/Thr/Tyr phosphoproteome of a reviving spore. The phosphoproteome was found to chiefly comprise newly identified phosphorylation sites located within proteins involved in basic biological functions, such as transcription, translation, carbon metabolism, and spore specific determinants. Quantitative comparison of dormant and germinating spore phosphoproteomes revealed phosphorylation dynamics, indicating that phospho modifications could modulate protein activity during this cellular transition. Furthermore, by mutating select phosphorylation sites located within proteins representative of key biological processes, we established a functional connection between phosphorylation and the progression of spore revival. CONCLUSIONS: Herein, we provide, for the first time, a phosphoproteomic view of a germinating bacterial spore. We further show that the spore phosphoproteome is dynamic and present evidence that phosphorylation events play an integral role in facilitating spore revival. PMID- 26381122 TI - Induction of granulation tissue for the secretion of growth factors and the promotion of bone defect repair. AB - BACKGROUND: The use of the Masquelet technique in the repair of large bone defects has gained increased acceptance in recent years. The core of this technique is the induction of granulation tissue membrane formation and the implantation of an autologous cancellous bone to reconstruct bone defects in the membrane. In this study, we purpose to explore the structure of induced membrane and the content of growth factors as well to compare between the structure and the effects on osteogenesis of induced membranes and the periosteum in animal models. METHODS: Bilateral radial bone defects were generated in 32 healthy adult rabbits. The defects were implanted with bone cement. The induced membranes and periosteum were removed after 2, 4, 6, and 8 weeks. Thereafter, hematoxylin-eosin staining (HE) and an enzyme-linked immunosorbent assay (ELISA) were performed to detect vascular endothelial growth factor (VEGF), angiotensin II (ANG-II), bone morphogenetic protein 2 (BMP2), fibroblast growth factor 2 (FGF2), and prostaglandin E2 (PGE2). Proteins isolated from total cell lysates were cultured with mesenchymal stem cells to test the cell proliferation and alkaline phosphatase activity using epimysium as a control. RESULTS: The induced membrane and periosteum exhibited similar structures and growth factor levels after 4 and 6 weeks. The highest concentration of BMP-2 and VEGF in the induced membranes occurred in week 6, and FGF-2 and ANG-II concentrations peaked in week 4. The thickness and vascular density of induced membranes gradually decreased with time. CONCLUSION: Induced membrane matured between the 4th and the 6th week and secreted growth factors to promote osteogenesis. The matured induced membrane and periosteum had similar structures and abilities to promote the osteogenesis of mesenchymal stem cells. However, the induced membrane was thicker than the periosteum. PMID- 26381123 TI - Attention and executive function in children with and without single-suture craniosynostosis. AB - Children with single-suture craniosynostosis (SSC) have higher rates of learning disabilities and related neurocognitive problems than unaffected peers. Executive function (EF) and attention are thought to be areas of particular vulnerability, though studies to date have been limited by small sample sizes and a lack of control groups. We evaluated 179 school-aged children with SSC (cases) and 183 unaffected controls at an average age of 7 years using clinician-administered and parent and teacher report measures of EF and attention. Among children with SSC, we examined differences as a function of suture location (sagittal, metopic, unicoronal, or lambdoid) and age of corrective surgery. We used linear regression analyses, adjusted for potential confounders, to compare the two groups on all outcome measures. Cases scored lower than controls on most measures, though the magnitude of these differences was small and most were statistically insignificant. The largest relative deficit was on a measure of inhibitory control. Results changed little in sensitivity analyses adjusting for potential attrition bias and for the effects of developmental and academic interventions. Among cases, there were few differences in relation to the location of suture fusion or timing of surgery. Overall, we found limited evidence of broad deficits in EF or attention in children with SSC relative to unaffected controls. Neurocognitive development for children with SSC appears to be variable, across affected children and outcomes assessed. Further research is needed to understand the potential sources of this variability. PMID- 26381124 TI - The senescent methylome and its relationship with cancer, ageing and germline genetic variation in humans. AB - BACKGROUND: Cellular senescence is a stable arrest of proliferation and is considered a key component of processes associated with carcinogenesis and other ageing-related phenotypes. Here, we perform methylome analysis of actively dividing and deeply senescent normal human epithelial cells. RESULTS: We identify senescence-associated differentially methylated positions (senDMPs) from multiple experiments using cells from one donor. We find that human senDMP epigenetic signatures are positively and significantly correlated with both cancer and ageing-associated methylation dynamics. We also identify germline genetic variants, including those associated with the p16INK4A locus, which are associated with the presence of in vivo senDMP signatures. Importantly, we also demonstrate that a single senDMP signature can be effectively reversed in a newly developed protocol of transient senescence reversal. CONCLUSIONS: The senDMP signature has significant potential for understanding some of the key (epi)genetic etiological factors that may lead to cancer and age-related diseases in humans. PMID- 26381125 TI - Characterization of early transcriptional responses to cadmium in the root and leaf of Cd-resistant Salix matsudana Koidz. AB - BACKGROUND: Salix matsudana Koidz. is a fast growing tree species. It has a high cadmium (Cd) tolerance capacity, making it potentially suitable for phytoremediation. Presently, transcriptomic and physiological Cd response mechanisms are poorly understood. Transcriptomic analysis in early response to high (50 MUM) Cd levels was investigated in leaf and root of Cd-resistant S. matsudana Koidz.. RESULTS: Analysis of the response profiles demonstrate the existence of a complex transcriptional network in the root and leaf when exposed to Cd. The main response in the root involved up-regulation of genes associated with defence response via callose deposition in the cell wall and cell wall thickening. In the leaf, transcripts related to biotic stress signalling and secondary metabolism were activated. Additionally, many lignin and brassinosteroids synthesis pathway genes were induced mainly in the leaf, indicating that gene response to Cd was tissue-specific. The Cd transcriptome results were consistent with observed physiological changes. CONCLUSION: The sub localization, transcriptional network, and physiological regulation demonstrate the tissue-specific manner of Cd response, and provide a novel insight into in early response of tree species to Cd exposure. PMID- 26381126 TI - Validity of the Aboriginal children's health and well-being measure: Aaniish Naa Gegii? AB - BACKGROUND: Aboriginal children experience challenges to their health and well being, yet also have unique strengths. It has been difficult to accurately assess their health outcomes due to the lack of culturally relevant measures. The Aboriginal Children's Health and Well-Being Measure (ACHWM) was developed to address this gap. This paper describes the validity of the new measure. METHODS: We recruited First Nations children from one First Nation reserve in Canada. Participants were asked to complete the ACHWM independently using a computer tablet. Participants also completed the PedsQL. The ACHWM total score and 4 Quadrant scores were expected to have a moderate correlation of between 0.4 and 0.6 with the parallel PedsQL total score, domains (scale scores), and summary scores. RESULTS: Paired ACHWM and PedsQL scores were available for 48 participants. They had a mean age of 14.6 (range of 7 to 19) years and 60.4 % were girls. The Pearson's correlation between the total ACHWM score and a total PedsQL aggregate score was 0.52 (p = 0.0001). The correlations with the Physical Health Summary Scores and the Psychosocial Health Summary Scores were slightly lower range (r = 0.35 p = 0.016; and r = 0.51 p = 0.0002 respectively) and approached the expected range. The ACHWM Quadrant scores were moderately correlated with the parallel PedsQL domains ranging from r = 0.45 to r = 0.64 (p <= 0.001). The Spiritual Quadrant of the ACHWM did not have a parallel domain in the PedsQL. CONCLUSIONS: These results establish the validity of the ACHWM. The children gave this measure an Ojibway name, Aaniish Naa Gegii, meaning "how are you?". This measure is now ready for implementation, and will contribute to a better understanding of the health of Aboriginal children. PMID- 26381127 TI - Molecular and Phylogenetic analysis revealed new genotypes of Theileria annulata parasites from India. AB - BACKGROUND: Tick borne diseases impinge cattle worldwide causing mortality and resulting in huge economic losses. Theileriosis is one of the important tick borne diseases mainly caused by Theileria annulata and one of the commonly occurring infections among the livestock. T. annulata causes immense loss to the livestock industry and therefore, efficacious eradication and control strategies are needed for the control of the disease. Genetic diversity among T. annulata parasites is another important aspect which is overlooked in India. Thus, the present study aims to evaluate the prevalence along with genetic diversity and phylogeny of the prevailing T. annulata population of India. METHODS: Genomic DNA was extracted from cattle blood samples (n = 862) from different regions of Andhra Pradesh. Molecular diagnosis using T. annulata 18S rRNA based PCR was performed to detect parasites in cattle. Further, 18S rRNA gene was cloned and sequenced to determine similarity and diversity from the known T. annulata sequences. RESULTS: We observed an overall prevalence rate of 32.40 % T. annulata infection in Andhra Pradesh based on PCR assay. The sequence analysis revealed novel genotypes among the T. annulata strains from India. Thirteen strains showed closed proximity with a strain from China whereas one Indian strain showed similarity with a South African strain [Theileria sp (buffalo)] based on phylogenetic analysis. Nucleotide heterogeneity of the 18S rRNA sequence among the strains examined varied from 0.1 to 8.6 % when compared with the published strains. CONCLUSION: The present study provides us with the molecular prevalence of theileriosis, and will support the accomplishment of actions or in design of strategy to control theileriosis transmission to cattle. Additionally, it highlights the emergence of strains with novel genotypes from India. PMID- 26381128 TI - Borderline hypotension: how does it influence cerebral regional tissue oxygenation in preterm infants? AB - AIM: To monitor cerebral regional tissue oxygenation (crSO2) of preterm infants continuously and to analyze the influence of arterial hypotension on crSO2. METHODS: In this prospective, observational study crSO2, peripheral oxygen saturation (SpO2), heart rate (HR) and mean arterial blood pressure (MABP) were monitored continuously for 24 h, starting within the first 6 h after birth. Furthermore, cerebral fractional tissue oxygen extraction (cFTOE) was calculated. Preterm neonates with and without arterial hypotension (MABP below the gestational age in weeks) were compared to each other. RESULTS: Forty-six preterm infants could be analyzed, 17 with (33.4 +/- 1.9 weeks, 2016.5 +/- 548.5 g) and 29 without arterial hypotension (33.3 +/- 1.3 weeks, 1924.7 +/- 451.9 g). Altogether, we detected 30 episodes of hypotension, with a mean duration of 1.6 +/- 1.2 h per infant and a mean decrease in MABP of 2.2 +/- 0.9 mmHg. During hypotension mean crSO2 was 7 5 +/- 11%, 2 h prior to that 76 +/- 10% and 2 h after the hypotension 7 7 +/- 10%, therefore no significant alterations could be observed. Moreover, there was no significant difference in mean 24-h crSO2, SpO2 and cFTOE between the two groups. CONCLUSION: Mild short-term hypotensive episodes in preterm infants did not affect crSO2. This suggests that cerebral autoregulation is maintained in case of borderline-hypotension and may protect infants from cerebral injury. PMID- 26381129 TI - Oxidative stress and cancer; the role of hesperidin, a citrus natural bioflavonoid, as a cancer chemoprotective agent. AB - Cancer is the third cause of death worldwide, with complex etiology, and is defined as an uncontrolled growth of cells. A high proportion of cancer incidence and deaths are due to different environmental and genetic factors such as high body mass index, low fruit and vegetable intake, lack of physical activity, tobacco use, alcohol consumption, exposure to radiation, chronic infections, and heredity also. In addition, oxidative stress plays a crucial role in the pathophysiology of different types of cancer. Hence, screening and testing of more effective compounds with minimum side effects for the prevention and treatment of cancers started a few decades ago. Regarding this, much attention has been paid to natural antioxidants as a novel prevention and treatment strategy for cancer. Flavonoids are one of the most important ingredients in vegetables and fruits, especially in the genus Citrus. Hesperidin is a flavonone glycoside, belonging to the flavonoid family, which is widely found in Citrus species and acts as a potent antioxidant and anticancer agent. In the present review, we attempt to provide an overview and summarize the scientific literature about the cancer chemoprotective effects of hesperidin with an emphasis on its relation to the protection roles against oxidative stress. PMID- 26381130 TI - The filamentous fungal pellet and forces driving its formation. AB - Filamentous fungi play an important role not only in the bio-manufacturing of value-added products, but also in bioenergy and environmental research. The bioprocess manipulation of filamentous fungi is more difficult than that of other microbial species because of their different pellet morphologies and the presence of tangled mycelia under different cultivation conditions. Fungal pellets, which have the advantages of harvest ease, low fermentation broth viscosity and high yield of some proteins, have been used for a long time. Many attempts have been made to establish the relationship between pellet and product yield using quantitative approaches. Fungal pellet formation is attributed to the combination of electrostatic interactions, hydrophobicity and specific interactions from spore wall components. Electrostatic interactions result from van der Waals forces and negative charge repulsion from carboxyl groups in the spore wall structure. Electrostatic interactions are also affected by counter-ions (cations) and the physiologic conditions of spores that modify the carboxyl groups. Fungal aggregates are promoted by the hydrophobicity generated by hydrophobins, which form a hydrophobic coat that covers the spore. The specific interactions of spore wall components contribute to spore aggregation through salt bridging. A model of spore aggregation was proposed based on these forces. Additionally, some challenges were addressed, including the limitations of research techniques, the quantitative determination of forces and the complex information of biological systems, to clarify the mechanism of fungal pellet formation. PMID- 26381131 TI - Impact and Progression of Organ Dysfunction in Patients with Necrotizing Soft Tissue Infections: A Multicenter Study. AB - BACKGROUND: Necrotizing soft tissue infections (NSTI) represent a rare but devastating disease for which the systemic manifestations have been poorly characterized. In an effort to define an optimal endpoint for clinical trials in this condition, the objective of this study was to establish the pattern of organ dysfunction over time and determine the correlation between organ dysfunction and clinical outcome in patients with NSTI. METHODS: We conducted a multicenter, retrospective clinical study of patients with NSTI presenting to 12 academic medical centers in the U.S. during 2013. Patients with a diagnosis of NSTI confirmed by surgical findings were included. Organ dysfunction was assessed using a modified Sequential Organ Failure Assessment (SOFA) score (mSOFA: excluding liver) on admission and on hospital days 1, 2, 3, 7, 10, and 14. The presence of organ dysfunction on admission and resolution of organ dysfunction were correlated with clinical parameters, including intensive care unit (ICU) free days (of 28 d), ventilator-free days, number of debridements, and mortality rate. The incidence of acute kidney injury (AKI) and recovery also were assessed. RESULTS: There were 198 patients enrolled, of whom 62% were male, the mean age was 51 years, and 40% had monomicrobial infections. The mean mSOFA score on admission was 2.4 +/- 3.0, with 49% of the patients having a score >=2 and 35% a score of >=3. Patients typically demonstrated worsening of the mSOFA score over the first 24 h followed by gradual resolution. An mSOFA >=3 at admission was associated with a significant decrease in ventilator-free days (mean 20.1 vs. 25.6 days; p < 0.001); ICU-free days (15.2 vs. 23.1, p < 0.001); more debridements (mean 2.3 vs. 2.0; p = 0.11); a higher mortality rate (15.9% vs. 3.1%; p = 0.003); and a higher rate of AKI (59.4 vs. 35.9%; p < 0.001). The persistence of organ dysfunction (mSOFA >1) among survivors at day 14 was associated with fewer ICU-free days (17.8 vs. 23.6; p < 0.001) and ventilator free days (23.6 vs. 27; p = 0.001) and a lower recovery rate from AKI (38.7% vs. 81.3%; p < 0.001). CONCLUSION: Early development of systemic organ dysfunction in patients with NSTI is associated with higher morbidity and mortality rates. Failure of the resolution of organ dysfunction by day 14 forecasts a poor outcome. The mSOFA score may be a useful marker for patient selection for inclusion in interventional trials, and the resolution of organ dysfunction by day 14 may be an important clinical endpoint. PMID- 26381132 TI - Formononetin induces apoptosis of human osteosarcoma cell line U2OS by regulating the expression of Bcl-2, Bax and MiR-375 in vitro and in vivo. AB - BACKGROUND/AIMS: Phytoestrogens are known to prevent tumor progression by inhibiting proliferation and inducing apoptosis in cancer cells. Formononetin is one of the main components of red clover plants, and is considered as a typical phytoestrogen. This study investigates formononetin induction of apoptosis of human osteosarcoma cell line U2OS by regulating Bcl-2 and Bax expression in vitro and in vivo. METHODS: U2OS cells were treated with different concentrations of formononetin and the proliferation of the cells was measured using an MTT assay. Cell apoptosis was examined by flow cytometry. The levels of miR-375, Bax and Bcl 2 protein expression in treated cells were determined by Western blot and RT-PCR. The antitumor activity of formononetin was also evaluated in vivo in nude mice bearing orthotopic tumor implants. RESULTS: High concentrations of formononetin significantly suppress the proliferation of U2OS cells and induce cell apoptosis. Moreover, compared to control group the expression of Bcl-2 and miR-375 decreases with formononetin in the U2OS cells, while Bax increases. CONCLUSION: Formononetin has inhibitory effects on the proliferation of U2SO cells, both in vitro and in vivo. This antitumor effect is directly correlated with formononetin concentration. PMID- 26381133 TI - Morphological Changes in the Overall Mycobacterium tuberculosis H37Ra Cell Shape and Cytoplasm Homogeneity due to Mutellina purpurea L. Essential Oil and Its Main Constituents. AB - OBJECTIVE: The aim of this study was to evaluate the antimycobacterial activity of the essential oil (EO) of Mutellina purpurea L. and its main constituents against the M. tuberculosis H37Ra strain. MATERIALS AND METHODS: The M. purpurea EO was obtained by hydrodistillation, while its main constituents were purchased. The minimal inhibitory concentration values were determined by the log2 dilution method. Visualization of the effects of the tested substances on M. tuberculosis was performed using a transmission electron microscope (TEM). Mathematical shape descriptors such as area, circularity, aspect ratio and roundness were calculated to describe morphological changes in bacterial cell shape. RESULTS: The EO of M.purpurea and all substances tested in this experiment showed a significant antimycobacterial activity. The most active was alpha-pinene followed by bisabolol and myrcene (8, 16 and 32 ug/ml, respectively). The EO and limonene exhibited the same antimicrobial activity (64 ug/ml). The TEM images and shape descriptors showed significant changes in the overall tuberculosis cell shape and cytoplasm homogeneity (uniformity and consistency) CONCLUSIONS: In this study, the low molecular weight compounds of mono- and sesquiterpenes penetrated/destabilized the complex mycobacterial cell wall and decreased its viability. There is a need for further experiments to explain the mechanism of action of these small particles. PMID- 26381134 TI - Concise postsynthetic preparation of oligonucleotide-oligopeptide conjugates through facile disulfide bond formation. AB - BACKGROUND: Despite recent advances, major hurdles still need to be cleared for widespread application of therapeutic antisense technologies. In particular, pharmacokinetic properties and efficient cellular uptake need to be improved through chemical derivatization or bioconjugation. RESULTS: The 2'-O-thioethylene nucleotide building block affords easy implementation into standard oligonucleotide synthesis protocols and was used to attach oligolysine chains to phosphodiester oligonucleotides by direct reaction with S-sulfonate protected peptides. Efficient gene silencing was induced in a cell culture model after transfection reagent-free application of the conjugates. CONCLUSION: A facile optimized procedure for generating oligonucleotide-peptide conjugates was established. The attachment of short basic peptides via a labile linker is sufficient to enhance membrane permeability of oligonucleotides and result in successful gene silencing. PMID- 26381135 TI - Highly Pathogenic H5N1 and Novel H7N9 Influenza A Viruses Induce More Profound Proteomic Host Responses than Seasonal and Pandemic H1N1 Strains. AB - Influenza A viruses (IAV) are important human and animal pathogens with potential for causing pandemics. IAVs exhibit a wide spectrum of clinical illness in humans, from relatively mild infections by seasonal strains to acute respiratory distress syndrome during infections with some highly pathogenic avian influenza (HPAI) viruses. In the present study, we infected A549 human cells with seasonal H1N1 (sH1N1), 2009 pandemic H1N1 (pdmH1N1), or novel H7N9 and HPAI H5N1 strains. We used multiplexed isobaric tags for relative and absolute quantification to measure proteomic host responses to these different strains at 1, 3, and 6 h post infection. Our analyses revealed that both H7N9 and H5N1 strains induced more profound changes to the A549 global proteome compared to those with low pathogenicity H1N1 virus infection, which correlates with the higher pathogenicity these strains exhibit at the organismal level. Bioinformatics analysis revealed important modulation of the nuclear factor erythroid 2-related factor 2 (NRF2) oxidative stress response in infection. Cellular fractionation and Western blotting suggested that the phosphorylated form of NRF2 is not imported to the nucleus in H5N1 and H7N9 virus infections. Fibronectin was also strongly inhibited in infection with H5N1 and H7N9 strains. This is the first known comparative proteomic study of the host response to H7N9, H5N1, and H1N1 viruses and the first time NRF2 is shown to be implicated in infection with highly pathogenic strains of influenza. PMID- 26381136 TI - Bioactives in Commonly Consumed Cereal Grains: Implications for Oxidative Stress and Inflammation. AB - Oxidative stress and inflammation are closely linked to various chronic diseases. Thus, targeting this axis of oxidative stress and inflammation is a particularly interesting area of study for reducing the risk of chronic diseases, including, but not limited to, metabolic disorders, cancer, cardiovascular disease, and Alzheimer's disease. It is well known that antioxidants play a pivotal role in tuning this axis. In this review, we introduce five different cereal grains, which are the most commonly consumed throughout the world and are functionally reported to have antioxidant activity: oat (Avena spp.), barley (Hordeum spp.), rice (Oryza spp.), wheat (Triticum spp.), and rye (Secale spp.). Bioactive components of these grains, partial grains or whole grains, have demonstrated antioxidant and anti-inflammatory activities in cells and animals. Although further study is required to establish their efficacy for treating patients with chronic diseases, we suggest that grains, which are a great source of antioxidants, have potential in the prevention of oxidative stress and inflammation-related chronic diseases. PMID- 26381137 TI - Nevus sebaceus: a clinicopathological study of 168 cases and review of the literature. AB - BACKGROUND: Nevus sebaceus is a hamartoma composed of abnormal epidermal and dermal components with clinical and histopathological features that change with aging. Prophylactic excision of the lesion was advised historically considering its potential for giving rise to malignant tumors. However, whether early prophylactic excision should be performed has been questioned recently as most of the tumors have been found to be benign in origin. METHODS: The histopathologic features of 168 patients with nevus sebaceus were reviewed to determine the frequency of different histologic features as well as associated neoplastic growths. RESULTS: Acanthosis, papillomatosis, and basal layer pigmentation were the most frequent findings. Hyperplastic changes of the sebaceous glands became obvious during the second decade and were present in 60% of the specimens from individuals older than 20. Inflammatory infiltrate was almost invariably present. Skin adnexal changes were frequently noted, including sebaceous gland hyperplasia (93.5%) and primitive hair follicles (76.8%). In 88.5% of scalp lesions, markedly decreased terminal hair was observed. Ectopic apocrine glands were present in 55.4% of specimens, while 24.4% showed anomalous ductal sweat gland structures resembling eccrine hyperplasia. Neoplastic changes were detected in nine cases, including four trichoblastomas, three tricholemmomas, and two syringocystadenoma papilliferums. CONCLUSION: Development of malignancies in sebaceus nevi is a rare phenomenon, and decision for excision of the lesion should be made after thorough evaluation of the pros and cons. PMID- 26381138 TI - Developing a prognostic model for patients with localized osteosarcoma treated with uniform chemotherapy protocol without high dose methotrexate: A single center experience of 237 patients. AB - BACKGROUND: Studies of baseline prognostic factors in patients with localized osteosarcoma treated without high dose methotrexate are limited. METHODS: This is single-institutional review of localized osteosarcoma patients treated without high dose methotrexate between June 2003-December 2012. A multivariate analysis of impact of baseline and treatment characteristics on outcome was performed and a prognostic model was developed based solely on baseline factors for predicting event-free survival (EFS) and overall survival (OS). RESULTS: Of 237 patients with median age of 17 years (range 2-66 yrs), neoadjuvant chemotherapy (NACT) was administered in 220 (92.82%) patients. Post NACT, 200/237 (84.38%) patients underwent surgery. At 30 months median follow-up, 5-year EFS and OS were 36.60 +/ 0.03%, and 50.33 +/- 0.04%, respectively. In multivariate analysis, baseline factors including duration of symptom >4 months (P < 0.001) and good performance status (PS) (P < 0.001) predicted better EFS whereas good PS (P = 0.01) and normal serum alkaline phosphatase (SAP) (P = 0.03) predicted better OS. The 5 year EFS without any risk factor (symptom duration <4 months, PS>1) was 58.7 +/- 0.1%, with either one factor 31.5 +/- 0.1% and with both factors 21.9 +/- 0.1%. The 5-year OS without any risk factor (PS>1, elevated SAP) was 66.9 +/- 0.1%, with either one factor 57.9 +/- 0.1% and with both factors 25.6 +/- 0.1%. CONCLUSIONS: This prognostic model assists in categorizing risk-groups within localized osteosarcoma. PMID- 26381139 TI - Advancing a multidisciplinary research framework on school environment, occupant health, and performance. PMID- 26381140 TI - The Influence of Adult Attachment on Patient Self-Management in Primary Care--The Need for a Personalized Approach and Patient-Centred Care. AB - OBJECTIVE: Self-management strategies are essential elements of evidence-based treatment in patients with chronic conditions in primary care. Our objective was to analyse different self-management skills and behaviours and their association to adult attachment in primary care patients with multiple chronic conditions. METHODS: In the apricare study (Adult Attachment in Primary Care) we used a prospective longitudinal design to examine the association between adult attachment and self-management in primary care patients with multimorbidity. The attachment dimensions avoidance and anxiety were measured using the ECR-RD. Self management skills were measured by the FERUS (motivation to change, coping, self efficacy, hope, social support) and self-management-behaviour by the DSMQ (glucose management, dietary control, physical activity, health-care use). Clinical diagnosis and severity of disease were assessed by the patients' GPs. Multivariate analyses (GLM) were used to assess the relationship between the dimensions of adult attachment and patient self-management. RESULTS: 219 patients in primary care with multiple chronic conditions (type II diabetes, hypertension and at least one other chronic condition) between the ages of 50 and 85 were included in the study. The attachment dimension anxiety was positively associated with motivation to change and negatively associated with coping, self-efficacy and hope, dietary control and physical activity. Avoidance was negatively associated with coping, self-efficacy, social support and health care use. CONCLUSION: The two attachment dimensions anxiety and avoidance are associated with different components of self-management. A personalized, attachment-based view on patients with chronic diseases could be the key to effective, individual self-management approaches in primary care. PMID- 26381141 TI - Bayesian Wavelet Shrinkage of the Haar-Fisz Transformed Wavelet Periodogram. AB - It is increasingly being realised that many real world time series are not stationary and exhibit evolving second-order autocovariance or spectral structure. This article introduces a Bayesian approach for modelling the evolving wavelet spectrum of a locally stationary wavelet time series. Our new method works by combining the advantages of a Haar-Fisz transformed spectrum with a simple, but powerful, Bayesian wavelet shrinkage method. Our new method produces excellent and stable spectral estimates and this is demonstrated via simulated data and on differenced infant electrocardiogram data. A major additional benefit of the Bayesian paradigm is that we obtain rigorous and useful credible intervals of the evolving spectral structure. We show how the Bayesian credible intervals provide extra insight into the infant electrocardiogram data. PMID- 26381143 TI - Identification of a Potential Regulatory Variant for Colorectal Cancer Risk Mapping to Chromosome 5q31.1: A Post-GWAS Study. AB - Large-scale genome-wide association studies (GWAS) have established chromosome 5q31.1 as a susceptibility locus for colorectal cancer (CRC), which was still lack of causal genetic variants. We searched potentially regulatory single nucleotide polymorphisms (SNPs) in the overlap region between linkage disequilibrium (LD) block of 5q31.1 and regulatory elements predicted by histone modifications, then tested their association with CRC via a case-control study. Among three candidate common variants, we found rs17716310 conferred significantly (heterozygous model: OR = 1.273, 95% confidence interval (95%CI) = 1.016-1.595, P = 0.036) and marginally (dominant model: OR = 1.238, 95%CI = 1.000 1.532, P = 0.050) increase risk for CRC in a Chinese population including 695 cases and 709 controls. This variation was suggested to be regulatory altering the activity of enhancer that control PITX1 expression. Using epigenetic information such as chromatin immunoprecipitation-sequencing (ChIP-seq) data might help researchers to interpret the results of GWAS and locate causal variants for diseases in post-GWAS era. PMID- 26381142 TI - Does Glucagon-like Peptide-1 Ameliorate Oxidative Stress in Diabetes? Evidence Based on Experimental and Clinical Studies. AB - Glucagon-like peptide-1 (GLP-1) has shown to influence the oxidative stress status in a number of in vitro, in vivo and clinical studies. Well-known effects of GLP-1 including better glycemic control, decreased food intake, increased insulin release and increased insulin sensitivity may indirectly contribute to this phenomenon, but glucose-independent effects on ROS level, production and antioxidant capacity have been suggested to also play a role. The potential 'antioxidant' activity of GLP-1 along with other proposed glucose-independent modes of action related to ameliorating redox imbalance remains a controversial topic but could hold a therapeutic potential against micro- and macrovascular diabetic complications. This review discusses the presently available knowledge from experimental and clinical studies on the effects of GLP-1 on oxidative stress in diabetes and diabetes-related complications. PMID- 26381144 TI - Propofol Increases Host Susceptibility to Microbial Infection by Reducing Subpopulations of Mature Immune Effector Cells at Sites of Infection. AB - Anesthetics are known to modulate host immune responses, but separating the variables of surgery from anesthesia when analyzing hospital acquired infections is often difficult. Here, the bacterial pathogen Listeria monocytogenes (Lm) was used to assess the impact of the common anesthetic propofol on host susceptibility to infection. Brief sedation of mice with physiologically relevant concentrations of propofol increased bacterial burdens in target organs by more than 10,000-fold relative to infected control animals. The adverse effects of propofol sedation on immune clearance of Lm persisted after recovery from sedation, as animals given the drug remained susceptible to infection for days following anesthesia. In contrast to propofol, sedation with alternative anesthetics such as ketamine/xylazine or pentobarbital did not increase susceptibility to systemic Lm infection. Propofol altered systemic cytokine and chemokine expression during infection, and prevented effective bacterial clearance by inhibiting the recruitment and/or activity of immune effector cells at sites of infection. Propofol exposure induced a marked reduction in marginal zone macrophages in the spleens of Lm infected mice, resulting in bacterial dissemination into deep tissue. Propofol also significantly increased mouse kidney abscess formation following infection with the common nosocomial pathogen Staphylococcus aureus. Taken together, these data indicate that even brief exposure to propofol severely compromises host resistance to microbial infection for days after recovery from sedation. PMID- 26381145 TI - The Impact of Iterative Reconstruction on Computed Tomography Radiation Dosimetry: Evaluation in a Routine Clinical Setting. AB - PURPOSE: To evaluate the effect of introduction of iterative reconstruction as a mandated software upgrade on radiation dosimetry in routine clinical practice over a range of computed tomography examinations. METHODS: Random samples of scanning data were extracted from a centralised Picture Archiving Communication System pertaining to 10 commonly performed computed tomography examination types undertaken at two hospitals in Western Australia, before and after the introduction of iterative reconstruction. Changes in the mean dose length product and effective dose were evaluated along with estimations of associated changes to annual cancer incidence. RESULTS: We observed statistically significant reductions in the effective radiation dose for head computed tomography (22-27%) consistent with those reported in the literature. In contrast the reductions observed for non-contrast chest (37-47%); chest pulmonary embolism study (28%), chest/abdominal/pelvic study (16%) and thoracic spine (39%) computed tomography. Statistically significant reductions in radiation dose were not identified in angiographic computed tomography. Dose reductions translated to substantial lowering of the lifetime attributable risk, especially for younger females, and estimated numbers of incident cancers. CONCLUSION: Reduction of CT dose is a priority Iterative reconstruction algorithms have the potential to significantly assist with dose reduction across a range of protocols. However, this reduction in dose is achieved via reductions in image noise. Fully realising the potential dose reduction of iterative reconstruction requires the adjustment of image factors and forgoing the noise reduction potential of the iterative algorithm. Our study has demonstrated a reduction in radiation dose for some scanning protocols, but not to the extent experimental studies had previously shown or in all protocols expected, raising questions about the extent to which iterative reconstruction achieves dose reduction in real world clinical practice. PMID- 26381146 TI - Factors Affecting Use and Delay (>=8 Weeks) of Adjuvant Chemotherapy after Colorectal Cancer Surgery and the Impact of Chemotherapy-Use and Delay on Oncologic Outcomes. AB - PURPOSE: To evaluate factors affecting the use and delay >=8 weeks of adjuvant chemotherapy and the impact of chemotherapy use and delay on survival. METHODS: Between 2005 and 2012, consecutive patients with stage II and III colorectal cancer who were treated with major curative resection were enrolled. RESULTS: Among 750 patients with stage II (n = 318) and III (n = 432) disease, 153 (20.4%) did not receive chemotherapy. Among 597 patients with adjuvant chemotherapy, 31 (5.2%) began chemotherapy 8 weeks or more after surgery. Factors associated with not receiving chemotherapy were: age >=80 years (hazard ratio [HR] = 5.2), American Society of Anesthesiologists score >=3 (HR = 1.9), underlying cerebrovascular disease (HR = 1.7), stage II disease (HR = 2.0), presence of postoperative complications (HR = 2.2), or intensive care unit admission (HR = 2.4). Factors associated with chemotherapy delay >=8 weeks were: male sex (HR = 4.2), rectal primary cancer (HR = 5.4), or presence of postoperative complications (HR = 2.5). Independent prognostic factors for overall survival included TNM III stage (HR = 2.04) and chemotherapy delay >=8 weeks (HR = 0.39) or <8 weeks (HR = 0.22). Independent prognostic factors for recurrence-free survival were TNM III stage (HR = 2.26) and chemotherapy delay <8 weeks (HR = 0.35). CONCLUSIONS: Postoperative complications were associated with both lack of and delayed chemotherapy. Timely initiation of chemotherapy, defined as <8 weeks, was a favorable prognostic factor for overall and recurrence-free survival. To increase the proportion of patients receiving chemotherapy and timely initiation of chemotherapy, surgical complications should be minimized after curative resection. PMID- 26381147 TI - Using Visual Methods to Understand Physical Activity Maintenance following Cardiac Rehabilitation. AB - Few studies have explored the factors associated with long-term maintenance of exercise following cardiac rehabilitation. The present study used auto photography and interviews to explore the factors that influence motivation and continued participation in physical activity among post cardiac rehabilitation patients. Twenty-three semi-structured interviews were conducted alongside participant-selected photographs or drawings with participants that had continued participation in physical activity for at least two years following the cardiac rehabilitation programme. Participants were recruited from circuit training classes in East Sussex in the UK. Thematic content analysis revealed seven main themes: fear of death and ill health avoidance, critical incidents, overcoming aging, social influences, being able to enjoy life, provision of routine and structure, enjoyment and psychological well-being. Fear of death, illness avoidance, overcoming aging, and being able to enjoy life were powerful motives for continued participation in exercise. The social nature of the exercise class was also identified as a key facilitator of continued participation. Group-based exercise suited those that continued exercise participation post cardiac rehabilitation and fostered adherence. PMID- 26381148 TI - Incorporation of nested frailties into semiparametric multi-state models. AB - Proportional hazards models are among the most popular regression models in survival analysis. Multi-state models generalize them by jointly considering different types of events and their interrelations, whereas frailty models incorporate random effects to account for unobserved risk factors, possibly shared by clusters of subjects. The integration of multi-state and frailty methodology is an interesting way to control for unobserved heterogeneity in the presence of complex event history structures and is particularly appealing for multicenter clinical trials. We propose the incorporation of correlated frailties in the transition-specific hazard function, thanks to a nested hierarchy. We studied a semiparametric estimation approach based on maximum integrated partial likelihood. We show in a simulation study that the nested frailty multi-state model improves the estimation of the effect of covariates, as well as the coverage probability of their confidence intervals. We present a case study concerning a prostate cancer multicenter clinical trial. The multi-state nature of the model allows us to evidence the effect of treatment on death taking into account intermediate events. PMID- 26381149 TI - Consistent Richness-Biomass Relationship across Environmental Gradients in a Marine Macroalgal-Dominated Subtidal Community on the Western Antarctic Peninsula. AB - Biodiversity loss has spurred the biodiversity-ecosystem functioning research over a range of ecosystems. In Antarctica, however, the relationship of taxonomic and functional diversity with ecosystem properties (e.g., community biomass) has received less attention, despite the presence of sharp and dynamic environmental stress gradients that might modulate these properties. Here, we investigated whether the richness-biomass relationship in macrobenthic subtidal communities is still apparent after accounting for environmental stress gradients in Fildes Bay, King George Island, Antarctica. Measurements of biomass of mobile and sessile macrobenthic taxa were conducted in the austral summer 2013/4 across two environmental stress gradients: distance from nearest glaciers and subtidal depth (from 5 to 30 m). In general, community biomass increased with distance from glaciers and water depth. However, generalised additive models showed that distance from glaciers and depth accounted for negligible proportions of variation in the number of functional groups (i.e., functional richness) and community biomass when compared to taxonomic richness. Functional richness and community biomass were positive and saturating functions of taxonomic richness. Large endemic, canopy-forming brown algae of the order Desmarestiales dominated the community biomass across both gradients. Accordingly, differences in the composition of taxa accounted for a significant and large proportion (51%) of variation in community biomass in comparison with functional richness (10%). Our results suggest that the environmental factors here analysed may be less important than biodiversity in shaping mesoscale (several km) biomass patterns in this Antarctic system. We suggest that further manipulative, hypothesis-driven research should address the role of biodiversity and species' functional traits in the responses of Antarctic subtidal communities to environmental variation. PMID- 26381150 TI - Pediatric weekend admission and increased unplanned readmission rates. AB - Outcomes for patients hospitalized on weekends are often worse for adults-the so called "weekend effect." Less is known about the weekend effect for children. We examined 55,383 hospitalizations at a tertiary care children's hospital. We used logistic regression to examine the associations of weekend admission and weekend discharge with unplanned 30-day readmission. We adjusted analyses for patient and hospitalization characteristics including number of complex chronic conditions, technology dependency, and length of stay. The 30-day unplanned readmission rate was 10.3%. Children admitted on the weekend had significantly higher odds of unplanned readmission compared to children admitted on weekdays (adjusted odds ratio = 1.09 [95% confidence interval: 1.004-1.18]). In contrast, being discharged on the weekend was not associated with readmission. In conclusion, children admitted on the weekend have higher rates of 30-day unplanned readmission than children admitted during the week, suggesting care differences on the weekend related to initial clinical management rather than discharge planning. PMID- 26381151 TI - The SELF trial: A self-efficacy-based behavioral intervention trial for weight loss maintenance. AB - OBJECTIVE: The SELF Trial examined the effect of adding individual self-efficacy (SE) enhancement sessions to standard behavioral weight loss treatment (SBT). METHODS: Participants were randomly assigned to SBT or SBT plus SE sessions (SBT+SE). Outcome measures were weight loss maintenance, quality of life, intervention adherence, and self-efficacy at 12 and 18 months. RESULTS: The sample (N = 130) was female (83.08%) with a mean (SD) body mass index of 33.15 (4.11) kg m(2) . There was a significant time effect for percent weight change (P = 0.002) yet no significant group or group-by-time effects. The weight loss for the SBT+SE group was 8.38% (7.48) at 12 months and 8.00% (7.87) at 18 months, with no significant difference between the two time points (P = 0.06). However, weight loss for the SBT group was 6.95% (6.67) at 12 months and 5.96% (7.35) at 18 months, which was significantly different between the two time points (P = 0.005), indicating that the SBT group had significant weight regain. CONCLUSIONS: Both groups achieved clinically significant weight loss. The group receiving an intervention targeting enhanced self-efficacy had greater weight loss maintenance whereas the SBT group demonstrated significant weight regain possibly related to the greater attention provided to the SBT+SE group. PMID- 26381152 TI - Mechanical Loading Stimulates Expression of Collagen Cross-Linking Associated Enzymes in Periodontal Ligament. AB - Type I collagen, a major extracellular component of the periodontal ligament (PDL), is post-translationally modified by a series of specific enzymes. Among the collagen-modifying enzymes, lysyl oxidase (LOX) is essential to initiate collagen cross-linking and lysyl hydroxylases (LHs) to regulate the cross-linking pathways that are important for tissue specific mechanical properties. The purpose of this study was to investigate the effects of mechanical loading on the expression of collagen-modifying enzymes and subsequent tissue changes in PDL. Primary human PDL cells were subjected to mechanical loading in a 3D collagen gel, and gene expression and collagen component were analyzed. Wistar rats were subjected to excessive occlusal loading with or without intra-peritoneal injection of a LOX inhibitor, beta-aminopropionitrile (BAPN). Upon mechanical loading, gene expression of LH2 and LOX was significantly elevated, while that of COL1A2 was not affected on hPDL-derived cells. The mechanical loading also elevated formation of collagen alpha-chain dimers in 3D culture. The numbers of LH2 and LOX positive cells in PDL were significantly increased in an excessive occlusal loading model. Notably, an increase of LH2-positive cells was observed only at the bone-side of PDL. Intensity of picrosirius red staining was increased by excessive occlusal loading, but significantly diminished by BAPN treatment. These results demonstrated that mechanical loading induced collagen maturation in PDL by up-regulating collagen-modifying enzymes and subsequent collagen cross linking which are important for PDL tissue maintenance. J. Cell. Physiol. 231: 926-933, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26381153 TI - [In Process Citation]. PMID- 26381154 TI - alpha2-containing GABA(A) receptors: a requirement for midazolam-escalated aggression and social approach in mice. AB - RATIONALE: Benzodiazepines (BZDs) are prescribed to reduce anxiety, agitation, and muscle spasms and for their sedative-hypnotic and anticonvulsant effects. Under specific conditions, BZDs escalate aggression in some individuals. Specific effects of BZDs have been linked to the alpha-subunit subtype composition of GABAA receptors. OBJECTIVES: Point-mutated mice rendered selectively insensitive to BZDs at alpha1-, alpha2-, or alpha3-containing GABAA receptors were used to determine which alpha-subunit subtypes are necessary for BZDs to escalate aggression and social approach and to reduce fear-motivated behavior. METHODS: During resident-intruder confrontations, male wild-type (WT) and point-mutated alpha1(H101R), alpha2(H101R), and alpha3(H126R) mice were treated with midazolam (0-1.7 mg/kg, i.p.) and evaluated for aggression in an unfamiliar environment. Separate midazolam-treated WT and point-mutated mice were assessed for social approach toward a female or investigated in a 6-day fear-potentiated startle procedure. RESULTS: Moderate doses of midazolam (0.3-0.56 mg/kg, i.p.) escalated aggression in WT and alpha3(H126R) mutants and increased social approach in WT and alpha1(H101R) mice. The highest dose of midazolam (1.0 mg/kg) reduced fear potentiated startle responding. All mice were sensitive to the sedative effect of midazolam (1.7 mg/kg) except alpha1(H101R) mutants. CONCLUSIONS: Midazolam requires BZD-sensitive alpha1- and alpha2-containing GABAA receptors in order to escalate aggression and alpha2- and alpha3-containing receptors to reduce social anxiety-like behavior. GABAA receptors containing the alpha1-subunit are crucial for BZD-induced sedation, while alpha2-containing GABAA receptors may be a shared site of action for the pro-aggressive and anxiolytic effects of BZDs. PMID- 26381155 TI - Effect of combined doses of Delta(9)-tetrahydrocannabinol (THC) and cannabidiolic acid (CBDA) on acute and anticipatory nausea using rat (Sprague- Dawley) models of conditioned gaping. AB - RATIONALE: Delta(9)-Tetrahydrocannabinol (THC) and cannabidiolic acid (CBDA) found in cannabis both reduce the distressing symptom of nausea, but their combined effects are not understood. OBJECTIVE: The potential of combined doses of THC and CBDA to reduce acute nausea and anticipatory nausea in rodent models was assessed. MATERIALS AND METHODS: For acute nausea, the potential of cannabinoid pretreatment(s) to reduce LiCl-induced nausea paired with saccharin was evaluated in a subsequent drug free taste reactivity test, followed by a taste avoidance test. For anticipatory nausea, the potential of the cannabinoid pretreatment(s) to reduce the expression of LiCl-induced contextually elicited conditioned gaping was evaluated. RESULTS: Combined subthreshold doses of THC (0.01 and 0.1 mg/kg) and CBDA (0.01 and 0.1 MUg/kg) reduced acute nausea. Higher doses of THC (1.0, 10 mg/kg) or CBDA (1.0, 10 MUg/kg) alone, as well as these combined doses also reduced acute nausea. THC (10 mg/kg) interfered with conditioned taste avoidance, an effect attenuated by CBDA (10 MUg/kg). On the other hand, combined subthreshold doses of THC (0.01 and 0.1 mg/kg) and CBDA (0.01 and 0.1 MUg/kg) did not suppress contextually elicited conditioned gaping in a test for anticipatory nausea. However, higher doses of THC (1.0, 10 mg/kg) or CBDA (1.0, 10 MUg/kg) alone, as well as these combined doses, also reduced anticipatory nausea. Only at the highest dose (10 mg/kg) did THC impair locomotor activity, but CBDA did not at any dose. CONCLUSIONS: Combined subthreshold doses of THC:CBDA are particularly effective as a treatment for acute nausea. At higher doses, CBDA may attenuate THC-induced interference with learning. PMID- 26381156 TI - Candida albicans Amphotericin B-Tolerant Persister Formation is Closely Related to Surface Adhesion. AB - Candida albicans persisters have so far been observed only in biofilm environment; the biofilm element(s) that trigger(s) persister formation are still unknown. In this study, we tried to further elucidate the possible relationship between C. albicans persisters and the early phases of biofilm formation, especially the surface adhesion phase. Three C. albicans strains were surveyed for the formation of persisters. We tested C. albicans persister formation dynamically at different time points during the process of adhesion and biofilm formation. The number of persister cells was determined based on an assessment of cell viability after amphotericin B treatment and colony-forming unit assay. None of the planktonic cultures contained persisters. Immediately following adhesion of C. albicans cells to the surface, persister cells emerged and the proportion of persisters reached a peak of 0.2-0.69 % in approximately 2-h biofilm. As the biofilm matured, the proportion of persisters decreased and was only 0.01-0.02 % by 24 h, while the number of persisters remained stable with no significant change. Persisters were not detected in the absence of an attachment surface which was pre-coated. Persisters were also absent in biofilms that were scraped to disrupt surface adhesion prior to amphotericin B treatment. These results indicate that C. albicans antifungal-tolerant persisters are produced mainly in surface adhesion phase and surface adhesion is required for the emergence and maintenance of C. albicans persisters. PMID- 26381157 TI - Transglycosidase-like activity of Mucor hiemalis endoglycosidase mutants enabling the synthesis of glycoconjugates using a natural glycan donor. AB - Glycan conversion of glycoprotein via the transglycosylation activity of endo beta-N-acetylglucosaminidase is a promising chemoenzymatic technology for the production of glycoproteins including bio-medicines with a homogeneous glycoform. Although Endo-M is a key enzyme in this process, its product undergoes rehydrolysis, which leads to a lower yield, and limits the practical application of this enzyme. We developed several Endo-M mutant enzymes including N175Q with glycosynthase-like activity and/or transglycosidase-like activity. We found that the Endo-M N175H mutant showed glycosynthase-like activity comparable to N175Q as well as transglycosidase-like activity superior to N175Q. Using a natural sialylglycopeptide as a donor substrate, N175H readily transferred the sialo glycan onto an N-acetylglucosamine residue attached to bovine ribonuclease B (RNase B), yielding a nonnative sialoglycosylated RNase B. These results demonstrate that use of Endo-M N175H is an alternative glycoengineering technique, which provides a relatively high yield of transglycosylation product and avoids the laborious synthesis of a sugar oxazoline as a donor substrate. PMID- 26381158 TI - Young people should be educated about the dangers of temporary tattoos. PMID- 26381159 TI - A New MRI-Based Pediatric Subcortical Segmentation Technique (PSST). AB - Volumetric and morphometric neuroimaging studies of the basal ganglia and thalamus in pediatric populations have utilized existing automated segmentation tools including FIRST (Functional Magnetic Resonance Imaging of the Brain's Integrated Registration and Segmentation Tool) and FreeSurfer. These segmentation packages, however, are mostly based on adult training data. Given that there are marked differences between the pediatric and adult brain, it is likely an age specific segmentation technique will produce more accurate segmentation results. In this study, we describe a new automated segmentation technique for analysis of 7-year-old basal ganglia and thalamus, called Pediatric Subcortical Segmentation Technique (PSST). PSST consists of a probabilistic 7-year-old subcortical gray matter atlas (accumbens, caudate, pallidum, putamen and thalamus) combined with a customized segmentation pipeline using existing tools: ANTs (Advanced Normalization Tools) and SPM (Statistical Parametric Mapping). The segmentation accuracy of PSST in 7-year-old data was compared against FIRST and FreeSurfer, relative to manual segmentation as the ground truth, utilizing spatial overlap (Dice's coefficient), volume correlation (intraclass correlation coefficient, ICC) and limits of agreement (Bland-Altman plots). PSST achieved spatial overlap scores >=90% and ICC scores >=0.77 when compared with manual segmentation, for all structures except the accumbens. Compared with FIRST and FreeSurfer, PSST showed higher spatial overlap (p FDR < 0.05) and ICC scores, with less volumetric bias according to Bland-Altman plots. PSST is a customized segmentation pipeline with an age-specific atlas that accurately segments typical and atypical basal ganglia and thalami at age 7 years, and has the potential to be applied to other pediatric datasets. PMID- 26381160 TI - Need for improved monitoring in patients with acromegaly. AB - Acromegaly is a rare and insidious disease characterized by the overproduction of growth hormone (GH) and insulin-like growth factor 1 (IGF1) and is most commonly due to a pituitary adenoma. Patients with acromegaly who experience prolonged exposure to elevated levels of GH and IGF1 have an increased mortality risk and progressive worsening of disease-related comorbidities. Multimodal treatment with surgery, medical therapy, and radiotherapy provides biochemical control, defined by recent acromegaly clinical guidelines from the Endocrine Society as a reduction of GH levels to <1.0 ng/ml and normalization of IGF1 levels, to a substantial proportion of patients and is associated with improved clinical outcomes. Patients with acromegaly, even those without clinical symptoms of disease, require long-term monitoring of GH and IGF1 levels if the benefits associated with biochemical control are to be maintained and the risk of developing recurrent disease is to be abated. However, suboptimal monitoring is common in patients with acromegaly, and this can have negative health effects due to delays in detection of recurrent disease and implementation of appropriate treatment. Because of the significant health consequences associated with prolonged exposure to elevated levels of GH and IGF1, optimal monitoring in patients with acromegaly is needed. This review article will discuss the biochemical assessments used for therapeutic monitoring in acromegaly, the importance of monitoring after surgery and medical therapy or radiotherapy, the consequences of suboptimal monitoring, and the need for improved monitoring algorithms for patients with acromegaly. PMID- 26381161 TI - Raman and Brillouin scattering studies of bulk 2H-WSe2. AB - Raman and Brillouin spectroscopy were used to probe optic and acoustic phonons in bulk 2H-WSe2. Raman spectra collected under different polarization conditions allowed assignment of spectral peaks to various first- and second-order processes. In contrast to some previous studies, a Raman peak at ~259 cm(-1)was found not to be due to the A(1g) mode but to a second-order process involving phonons at either the M or K point of the Brillouin zone. Resonance effects due to excitons were also observed in the Raman spectra. Brillouin spectra of 2H-WSe2 contain a single peak doublet arising from a Rayleigh surface mode propagating with a velocity of [Formula: see text] m s(-1). This value is comparable to that estimated from Density Functional Theory calculations and also to those for the transition metal diselenides 2H-TaSe2 and 2H-NbSe2. Unlike these two materials, however, peaks arising from scattering via the elasto-optic mechanism were not observed in Brillouin spectra of WSe2 despite its lower opacity. PMID- 26381162 TI - Revision of the Genus Pseudaethria Schaus (Lepidoptera, Erebidae). AB - The genus Pseudaethria Schaus is revised and redescribed based on morphological characters of male and female adults. Its type species, Pseudaethria cessogae Schaus, was found out to be a junior subjective synonym of Heliura cosmosomodes Dognin. Therefore, the new combination Pseudaethria cosmosomodes is proposed along with another one: Pseudaethria analis Gaede new combination. A lectotype is designated to P. cessogae, which was described from an undetermined number of specimens. The distribution of the species is discussed as well as its systematic placement. PMID- 26381163 TI - DNA Crossover Motifs Associated with Epigenetic Modifications Delineate Open Chromatin Regions in Arabidopsis. AB - The rate of crossover, the reciprocal exchanges of homologous chromosomal segments, is not uniform along chromosomes differing between male and female meiocytes. To better understand the factors regulating this variable landscape, we performed a detailed genetic and epigenetic analysis of 737 crossover events in Arabidopsis thaliana. Crossovers were more frequent than expected in promoters. Three DNA motifs enriched in crossover regions and less abundant in crossover-poor pericentric regions were identified. One of these motifs, the CCN repeat, was previously unknown in plants. The A-rich motif was preferentially associated with promoters, while the CCN repeat and the CTT repeat motifs were preferentially associated with genes. Analysis of epigenetic modifications around the motifs showed, in most cases, a specific epigenetic architecture. For example, we show that there is a peak of nucleosome occupancy and of H3K4me3 around the CCN and CTT repeat motifs while nucleosome occupancy was lowest around the A-rich motif. Cytosine methylation levels showed a gradual decrease within ~2 kb of the three motifs, being lowest at sites where crossover occurred. This landscape was conserved in the decreased DNA methylation1 mutant. In summary, the crossover motifs are associated with epigenetic landscapes corresponding to open chromatin and contributing to the nonuniformity of crossovers in Arabidopsis. PMID- 26381165 TI - Lack of Potential Pharmacokinetic and Pharmacodynamic Interactions Between Piragliatin, a Glucokinase Activator, and Simvastatin in Patients With Type 2 Diabetes Mellitus. AB - To evaluate the potential pharmacokinetic (PK) and pharmacodynamic (PD, glucose lowering effect) interaction between simvastatin and piragliatin, both CYP3A substrates, 30 patients with type 2 diabetes mellitus participated in this open label, randomized, 6-sequence, 3-way crossover (William's design) study. During 3 periods, patients were randomized to receive a single dose of 80 mg simvastatin alone, a single dose of 100 mg piragliatin alone, as well as single doses of 80 mg simvastatin and 100 mg piragliatin together. Primary PK and PD parameters were AUCs on dosing days. The ratio of geometric means (90% confidence intervals) of the AUCinf of piragliatin coadministered with simvastatin compared with piragliatin alone was 0.98 (0.92-1.05), whereas that of the AUCinf of simvastatin acid (active metabolite) coadministered with piragliatin compared with simvastatin alone, was 1.02 (0.90-1.16), suggesting lack of pharmacokinetic interaction between piragliatin and simvastatin. Piragliatin's glucose-lowering effect was not affected by coadministration of simvastatin. Overall, administration of piragliatin with simvastatin was without additional clinically relevant adverse effects as well as abnormality in laboratory tests, vital signs, and electrocardiogram parameters. Concomitant administration of simvastatin and piragliatin, both CYP3A substrates, has no clinically relevant effect on the pharmacokinetics of either piragliatin or simvastatin or on the pharmacodynamics for piragliatin. PMID- 26381164 TI - A robust and efficient method for estimating enzyme complex abundance and metabolic flux from expression data. AB - A major theme in constraint-based modeling is unifying experimental data, such as biochemical information about the reactions that can occur in a system or the composition and localization of enzyme complexes, with high-throughput data including expression data, metabolomics, or DNA sequencing. The desired result is to increase predictive capability and improve our understanding of metabolism. The approach typically employed when only gene (or protein) intensities are available is the creation of tissue-specific models, which reduces the available reactions in an organism model, and does not provide an objective function for the estimation of fluxes. We develop a method, flux assignment with LAD (least absolute deviation) convex objectives and normalization (FALCON), that employs metabolic network reconstructions along with expression data to estimate fluxes. In order to use such a method, accurate measures of enzyme complex abundance are needed, so we first present an algorithm that addresses quantification of complex abundance. Our extensions to prior techniques include the capability to work with large models and significantly improved run-time performance even for smaller models, an improved analysis of enzyme complex formation, the ability to handle large enzyme complex rules that may incorporate multiple isoforms, and either maintained or significantly improved correlation with experimentally measured fluxes. FALCON has been implemented in MATLAB and ATS, and can be downloaded from: https://github.com/bbarker/FALCON. ATS is not required to compile the software, as intermediate C source code is available. FALCON requires use of the COBRA Toolbox, also implemented in MATLAB. PMID- 26381166 TI - TRAP-rc, Translating Ribosome Affinity Purification from Rare Cell Populations of Drosophila Embryos. AB - Measuring levels of mRNAs in the process of translation in individual cells provides information on the proteins involved in cellular functions at a given point in time. The protocol dubbed Translating Ribosome Affinity Purification (TRAP) is able to capture this mRNA translation process in a cell-type-specific manner. Based on the affinity purification of polysomes carrying a tagged ribosomal subunit, TRAP can be applied to translatome analyses in individual cells, making it possible to compare cell types during the course of developmental processes or to track disease development progress and the impact of potential therapies at molecular level. Here we report an optimized version of the TRAP protocol, called TRAP-rc (rare cells), dedicated to identifying engaged in-translation RNAs from rare cell populations. TRAP-rc was validated using the Gal4/UAS targeting system in a restricted population of muscle cells in Drosophila embryos. This novel protocol allows the recovery of cell-type-specific RNA in sufficient quantities for global gene expression analytics such as microarrays or RNA-seq. The robustness of the protocol and the large collections of Gal4 drivers make TRAP-rc a highly versatile approach with potential applications in cell-specific genome-wide studies. PMID- 26381167 TI - Isolated proximal tibiofibular joint arthritis in a patient with juvenile idiopathic arthritis: A case report. AB - We report the case of a 14-year-old girl of juvenile idiopathic arthritis (JIA) with isolated and chronic proximal tibiofibular (PTF) joint arthritis. The clinical history, magnetic resonance imaging, and pathological findings of the patient are presented. We should be careful to evaluate the patient for chronic lateral knee pain, and consider concomitant evaluation for JIA, including rheumatoid arthritis. PMID- 26381169 TI - Foxp3-dependent transformation of human primary CD4+ T lymphocytes by the retroviral protein tax. AB - The retroviral Tax proteins of human T cell leukemia virus type 1 and 2 (HTLV-1 and -2) are highly homologous viral transactivators. Both viral proteins can immortalize human primary CD4+ memory T cells, but when expressed alone they rarely transform T cells. In the present study, we found that the Tax proteins displayed a differential ability to immortalize human CD4+Foxp3+ T cells with characteristic expression of CTLA-4 and GITR. Because epidermal growth factor receptor (EGFR) was reportedly expressed and activated in a subset of CD4+Foxp3+ T cells, we introduced an activated EGFR into Tax-immortalized CD4+Foxp3+ T cells. We observed that these modified cells were grown independently of exogenous IL-2, correlating with a T cell transformation phenotype. In Tax immortalized CD4+Foxp3- T cells, ectopic expression of Foxp3 was a prerequisite for Tax transformation of T cells. Accordingly, treatment of the transformed T cells with erlotinib, a selective inhibitor of EGFR, induced degradation of EGFR in lysosome, consequently causing T cell growth inhibition. Further, we identified autophagy as a crucial cellular survival pathway for the transformed T cells. Silencing key autophagy molecules including Beclin1, Atg5 and PI3 kinase class III (PI3KC3) resulted in drastic impairment of T cell growth. Our data, therefore, unveiled a previously unidentified role of Foxp3 in T cell transformation, providing a molecular basis for HTLV-1 transformation of CD4+Foxp3+ T cells. PMID- 26381168 TI - Individual prediction of chronic motor outcome in the acute post-stroke stage: Behavioral parameters versus functional imaging. AB - Several neurobiological factors have been found to correlate with functional recovery after brain lesions. However, predicting the individual potential of recovery remains difficult. Here we used multivariate support vector machine (SVM) classification to explore the prognostic value of functional magnetic resonance imaging (fMRI) to predict individual motor outcome at 4-6 months post stroke. To this end, 21 first-ever stroke patients with hand motor deficits participated in an fMRI hand motor task in the first few days post-stroke. Motor impairment was quantified assessing grip force and the Action Research Arm Test. Linear SVM classifiers were trained to predict good versus poor motor outcome of unseen new patients. We found that fMRI activity acquired in the first week post stroke correctly predicted the outcome for 86% of all patients. In contrast, the concurrent assessment of motor function provided 76% accuracy with low sensitivity (<60%). Furthermore, the outcome of patients with initially moderate impairment and high outcome variability could not be predicted based on motor tests. In contrast, fMRI provided 87.5% prediction accuracy in these patients. Classifications were driven by activity in ipsilesional motor areas and contralesional cerebellum. The accuracy of subacute fMRI data (two weeks post stroke), age, time post-stroke, lesion volume, and location were at 50%-chance level. In conclusion, multivariate decoding of fMRI data with SVM early after stroke enables a robust prediction of motor recovery. The potential for recovery is influenced by the initial dysfunction of the active motor system, particularly in those patients whose outcome cannot be predicted by behavioral tests. PMID- 26381170 TI - Pharmacology of hSlo3 channels and their contribution in the capacitation associated hyperpolarization of human sperm. AB - Slo3 channels (mSlo3) primarily mediate mouse sperm K(+) currents and are essential for the capacitation-associated hyperpolarization (CAH). Whether Slo3 and/or Slo1, two Slo family K(+) channels are functionally expressed in human sperm is controversial. Our recent pharmacological studies of the human sperm CAH suggested the participation of both. Lack of a detailed pharmacology of heterologously expressed human Slo3 (hSlo3) prevented precisely identifying the K(+) channel(s) involved. In the present report, we compare the pharmacological profile of expressed hSlo3 in CHO cells with that of the CAH to advance this matter. Whole-cell patch-clamp recordings showed that hSlo3 currents are inhibited: significantly by progesterone, Ba(2+) and quinidine; partially by Penitrem A and Charybdotoxin; and poorly by Iberiotoxin and Slotoxin. Surprisingly, hSlo3 currents were resistant to Clofilium and 60 mM TEA(+) which inhibit mSlo3. Pharmacological comparison of the CAH and hSlo3 profiles indicates in addition to hSlo3, other K(+) channels, possibly Slo1, may participate in CAH. The pharmacological profile of heterologously expressed hSlo3 channels differs from that of mSlo3 K(+) channels, consistent with species-specific differences observed among other sperm ion channels. While the pharmacological correlation analysis of the hSlo3 currents and the CAH confirmed the participation of hSlo3 channels, it suggests that additional K(+) channels may be involved, in particular Slo1 channels. PMID- 26381171 TI - Mouse somatic mutation orthologous to MELAS A3302G mutation in the mitochondrial tRNA(Leu(UUR)) gene confers respiration defects. AB - We searched for mtDNA harboring somatic mutations in mouse B82 cells, and found an A2748G mutation orthologous to the A3302G mutation in tRNA(Leu(UUR)) gene reported in a patient with MELAS, the most prevalent mitochondrial disease. We isolated subclones of B82 cells until we obtained one subclone harboring >95% A2748G mtDNA. Cytoplasmic transfer of A2748G mtDNA resulted in cotransfer of A2748G mtDNA and respiration defects into mouse ES cells. Thus, A2748G mtDNA is responsible for respiration defects, and the ES cells harboring A2748G mtDNA may be useful for generation of transmitochondrial mice harboring A2748G mtDNA as potential disease models of MELAS. PMID- 26381172 TI - Effects of lysine residues on structural characteristics and stability of tau proteins. AB - Pathological amyloid proteins have been implicated in neuro-degenerative diseases, specifically Alzheimer's, Parkinson's, Lewy-body diseases and prion related diseases. In prion related diseases, functional tau proteins can be transformed into pathological agents by environmental factors, including oxidative stress, inflammation, Abeta-mediated toxicity and covalent modification. These pathological agents are stable under physiological conditions and are not easily degraded. This un-degradable characteristic of tau proteins enables their utilization as functional materials to capturing the carbon dioxides. For the proper utilization of amyloid proteins as functional materials efficiently, a basic study regarding their structural characteristic is necessary. Here, we investigated the basic tau protein structure of wild-type (WT) and tau proteins with lysine residues mutation at glutamic residue (Q2K) on tau protein at atomistic scale. We also reported the size effect of both the WT and Q2K structures, which allowed us to identify the stability of those amyloid structures. PMID- 26381173 TI - Effect of DNMT inhibitor on bovine parthenogenetic embryo development. AB - DNA methylation catalyzed by DNA methyltransferase (DNMT) family plays an important role during mammal preimplanted embryo development. However, the effects of RG108, a DNMT inhibitor (DNMTi), on DNMT in the development of bovine preimplanted embryos are not fully elucidated. In this study, we investigated the role of RG108 on the development, dynamics of gene-specific DNA methylation and transcription of bovine parthenogenetic preimplantation embryos. We found that Dnmt1 and Dnmt3b showed highly transcription in parthenogenetic 2-cell embryos, and then the transcription levels decreased during the following development stages, whereas Dnmt3a was always maintained at a lower transcription level during bovine parthenogenetic preimplantation embryo development. Treatment with RG108 blocked the development of bovine parthenogenetic preimplantation embryos and induced hypomethylation in the embryos. RG108 decreased the methylation level of the Nanog gene promoter region, which caused activation of the Nanog gene in 8 cell embryos and increased the transcription level. RG108 also induced the hypomethylation of the repeat elements (satellite I and alpha-satellite), which may cause genome instability, increasing the number of apoptotic cells in the blastocysts and also the transcription level of the apoptotic gene Bax. These results indicate that RG108, a DNMT inhibitor (DNMTi), inhibits the development of bovine parthenogenetic preimplantation embryos, suggesting that the DNMT is necessary for bovine parthenogenetic preimplanatation embryo development. PMID- 26381174 TI - Autophagy regulated by prolyl isomerase Pin1 and phospho-Ser-GSK3alphabeta involved in protection of oral squamous cell carcinoma against cadmium toxicity. AB - Prolyl isomerase Pin1 plays an important role in cell proliferation and is overexpressed in many human tumors. However, its role in autophagy induction remains undefined. Here we show that Pin1 regulates cell survival via autophagy in cadmium (Cd)-exposed oral squamous cell carcinoma (OSCC). OSCC exposure to Cd induced autophagy, as demonstrated by the formation of green fluorescent punctae in transfected cells expressing GFP-conjugated microtubule-associated protein light chain 3 (LC3) and by LC3 flux in the presence of autophagy inhibitors. Suppression of Atg5 enhanced Cd-induced apoptosis, indicating that autophagy is involved in cell protection. In dose-response experiments, cleavage of procaspase 3, PARP-1, and LC3-II was induced by Cd with an IC50 of 45 MUM. Expression of Pin1 was decreased at or above the Cd IC50 value and was inversely correlated with the level of phospho(p)-Ser-GSK3alphabeta. Genetic or pharmacologic inhibition of Pin1 suppressed Cd-induced autophagy, but increased p-Akt-mediated p-Ser-GSK3alphabeta; this was reversed by overexpression of Pin1. However, suppression of GSK3alphabeta inhibited Cd-induced autophagy and induced apoptosis, which could be reversed by overexpression of GSK3beta. The PI3K inhibitor Ly294002 blocked p-Akt-mediated increases in p-Ser-GSK3alphabeta and autophagy and induced apoptosis. Therefore, p-Ser-GSK3alphabeta can directly regulate Cd-induced autophagy, although its function is suppressed by Pin1. Collectively, the present results indicate that targeting Pin1 and GSK3alphabeta at the same time could be an effective therapeutic tool for Cd-induced carcinogenesis. PMID- 26381175 TI - Endurance exercise training induces fat depot-specific differences in basal autophagic activity. AB - The purpose of this study was to uncover the effect of exercise training on the expression of autophagy marker proteins in epididymal white adipose tissue (eWAT), inguinal WAT (iWAT), and the stromal vascular fraction (SVF) collected from eWAT. Male Wistar rats aged 4-5 weeks were randomly divided into two groups, sedentary control (n = 7) and exercise-trained (n = 7). Rats in the exercise trained group were exercised on a treadmill set at a 5 degrees incline 5 days/week for 9 weeks. We determined that the expression levels of an autophagosome-associating form of microtubule-associated protein 1 light chain 3 (LC3)-II and of p62 were significantly higher in eWAT from exercise-trained than from control rats, while those of adipose-specific deletion of autophagy-related protein (ATG7) and lysosomal-associated membrane protein type 2A (LAMP2a) showed no difference between groups. However, in iWAT, the expression levels of LC3-II and ATG7 were significantly higher in exercise-trained than in control rats. The expression of p62 was highly correlated with that of peroxisome proliferator activated receptor gamma (PPARgamma), a master regulator of adipogenesis and lipid metabolism, in both WAT types (eWAT, r = 0.856, P < 0.05; iWAT, r = 0.762, P < 0.05), whereas LC3-II and PPARgamma levels were highly correlated in eWAT (r = 0.765, P < 0.05) but not in iWAT (r = -0.306, ns). In SVF, the expression levels of LC3II, ATG7, and LAMP2a were significantly higher in exercise-trained than in control rats. These results suggest that exercise training suppresses basal autophagy activity in eWAT, but that this activity is enhanced in iWAT and SVF collected from eWAT. Thus, the adaptation of basal autophagic activity following exercise training exhibits fat depot-specific differences. PMID- 26381176 TI - Ginsenoside Rb1 promotes browning through regulation of PPARgamma in 3T3-L1 adipocytes. AB - Browning of white adipocyte tissue (WAT) has received considerable attention due to its potential implication in preventing obesity and related comorbidities. Ginsenoside Rb1 is reported to improve glycolipid metabolism and reduce body weight in obese animals. However whether the body reducing effect mediates by browning effect remains unclear. For this purpose, 3T3-L1 adipocytes were used to study the effect of ginsenoside Rb1 on browning adipocytes specific genes and oxygen consumptions. The results demonstrate that 10 MUM of ginsenoside Rb1 increases basal glucose uptake and promoted browning evidenced by significant increases in mRNA expressions of UCP-1, PGC-1alpha and PRDM16 in 3T3-L1 mature adipocytes. Further, ginsenoside Rb1 also increases PPARgamma activity. And the browning effect is abrogated by GW9692, a PPARgamma antagonist. In addition, ginsenoside Rb1 increases basal respiration rate, ATP production and uncoupling capacity in 3T3-L1 adipocytes. Those effects are also blunted by GW9692. The results suggest that ginsenoside Rb1 promote browning of 3T3-L1 adipocytes through induction of PPARgamma. Our finding offer a new source to discover browning agonists and also useful to understand and extend the applications of ginseng and its constituents. PMID- 26381177 TI - Skeletal muscle-specific HMG-CoA reductase knockout mice exhibit rhabdomyolysis: A model for statin-induced myopathy. AB - HMG-CoA reductase (HMGCR) catalyzes the conversion of HMG-CoA to mevalonic acid (MVA); this is the rate-limiting enzyme of the mevalonate pathway that synthesizes cholesterol. Statins, HMGCR inhibitors, are widely used as cholesterol-reducing drugs. However, statin-induced myopathy is the most adverse side effect of statins. To eludicate the mechanisms underlying statin the myotoxicity and HMGCR function in the skeletal muscle, we developed the skeletal muscle-specific HMGCR knockout mice. Knockout mice exhibited postnatal myopathy with elevated serum creatine kinase levels and necrosis. Myopathy in knockout mice was completely rescued by the oral administration of MVA. These results suggest that skeletal muscle toxicity caused by statins is dependent on the deficiencies of HMGCR enzyme activity and downstream metabolites of the mevalonate pathway in skeletal muscles rather than the liver or other organs. PMID- 26381178 TI - PF-4708671, a specific inhibitor of p70 ribosomal S6 kinase 1, activates Nrf2 by promoting p62-dependent autophagic degradation of Keap1. AB - p70 ribosomal S6 kinase 1 (S6K1) is an important serine/threonine kinase and downstream target of the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway. PF-4708671 is a specific inhibitor of S6K1, and prevents S6K1 mediated phosphorylation of the S6 protein. PF-4708671 treatment often leads to apoptotic cell death. However, the protective mechanism against PF-4708671 induced cell death has not been elucidated. The nuclear factor erythroid 2 related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) pathway is essential for protecting cells against oxidative stress. p62, an adaptor protein in the autophagic process, enhances Nrf2 activation through the impairment of Keap1 activity. In this study, we showed that PF-4708671 induces autophagic Keap1 degradation-mediated Nrf2 activation in p62-dependent manner. Furthermore, p62 dependent Nrf2 activation plays a crucial role in protecting cells from PF 4708671-mediated apoptosis. PMID- 26381179 TI - DNA-PKcs interference sensitizes colorectal cancer cells to a mTOR kinase inhibitor WAY-600. AB - Colorectal cancer (CRC) is one leading contributor of cancer-related mortalities. Mammalian target of rapamycin (mTOR), existing in two complexes (mTORC1/2), is a valuable target for possible CRC interference. In the current study, we showed that WAY-600, a potent mTOR inhibitor, only exerted moderate activity against primary and HT-29 CRC cells. We proposed that DNA-dependent protein kinase catalytic subunit (DNA-PKcs) could be the major resistance factor of WAY-600 in CRC cells. DNA-PKcs inhibitors, including NU7026 and NU7441, dramatically enhanced WAY-600-induced cytotoxic and pro-apoptotic effect against the CRC cells. Further, WAY-600-exerted cytotoxicity was significantly increased in DNA PKcs-silenced (by targeted siRNA/shRNA) CRC cells, but was attenuated with DNA PKcs overexpression. Our evidence suggested that DNA-PKcs Thr-2609 phosphorylation might be critical for WAY-600's resistance. Mutation of this site through introducing a dominant negative DNA-PKcs (T2609A) dramatically potentiated WAY-600's sensitivity in HT-29 cells. Meanwhile, overexpression of protein phosphatase 5 (PP5) dephosphorylated DNA-PKcs at Thr-2609, and significantly increased WAY-600's sensitivity in HT-29 cells. In vivo, WAY-600 induced anti-HT-29 xenograft growth activity was significantly potentiated with NU7026 co-administration. These results suggest that DNA-PKcs could be the major resistance factor of WAY-600 in CRC cells. PMID- 26381180 TI - A high-sensitive HMab-2 specifically detects IDH1-R132H, the most common IDH mutation in gliomas. AB - Isocitrate dehydrogenase 1 (IDH1) mutations have been detected in gliomas and other tumors. Although IDH1 catalyzes the oxidative carboxylation of isocitrate to alpha-ketoglutarate (alpha-KG) in cytosol, mutated IDH1 proteins possess the ability to change alpha-KG into the oncometabolite D-2-hydroxyglutarate (D-2HG). Several monoclonal antibodies (mAbs) specific for IDH1 mutations have been established, such as H09, IMab-1, and HMab-1 against IDH1-R132H, which is the most frequent IDH1 mutation in gliomas. In this study, we established a novel high-sensitive mAb HMab-2, which reacts with IDH1-R132H but not with wild type IDH1 in ELISA. HMab-2 reacted only with IDH1-R132H, not with wild type IDH1/2 and other IDH1/2 mutants in Western-blot analysis. Furthermore, HMab-2 recognized IDH1-R132H more sensitively compared with our previously established HMab-1. HMab 2 detected endogenous IDH1-R132H protein expressed in glioblastoma in immunohistochemical analysis. HMab-2 is expected to be useful for the diagnosis of IDH1-R132H-bearing tumors. PMID- 26381181 TI - RNAi knockdown of fatty acid elongase1 alters fatty acid composition in Brassica napus. AB - The quality and end-use of oil from oilseed crops is determined by its fatty acid composition. In particular, the relative proportions of erucic and oleic acids are key selection traits for breeders. The goal of our research is to genetically improve the nutritional quality of Brassica napus cultivar CY2, the oil of which is high in erucic acid (about 40%) and low in oleic acid (about 20%). Here, we report the use of a seed-specific napin A promoter to drive the knockdown of BnFAE1 in transgenic CY2. Southern blotting results confirmed the presence of the transgene. RT-PCR analysis showed that the levels of BnFAE1 were greatly decreased in BnFAE1-Ri lines compared with the CY2 cultivar. Knockdown of BnFAE1 sharply decreased the levels of erucic acid (less than 3%), largely increased the contents of oleic acid (more than 60%) and slightly increased the polyunsaturated chain fatty acids. Compared with high erucic acid parents, expression of BnFAE1 was dramatically decreased in developing F1 seeds derived from reciprocally crossed BnFAE1-Ri lines and high erucic acid cultivars. In addition, F1 seeds derived from reciprocal crosses between BnFAE1-Ri lines and high erucic acid cultivars showed significantly increased oleic acid (more than 52%) and sharply decreased erucic acid (less than 4%), demonstrating that the RNAi construct of BnFAE1 can effectively interfere with the target gene in F1 seeds. Taken together, our results demonstrate that BnFAE1 is a reliable target for genetic improvement of rapeseed in seed oil quality promotion. PMID- 26381182 TI - Metacognitive processes in psychometrically defined schizotypy. AB - Metacognitive abnormalities have been implicated in the experience of psychotic symptoms; however, the process through which this occurs remains unclear. The aim of this study was to clarify the association of self-reported schizotypy with metacognitive beliefs and neural activity related to higher-order cognition. Event-related potentials (ERPs) including the error-related negativity (ERN) and error positivity (Pe) were recorded during a Flanker task in 20 controls and 22 individuals with high self-reported schizotypy on the Schizotypal Personality Questionnaire-Brief Revised (SPQ-BR). Participants continuously evaluated their task performance and completed the Metacognitions Questionnaire-30 (MCQ-30). The high schizotypy group demonstrated higher scores on all subscales of the MCQ-30. In contrast, task performance, accuracy of self-performance evaluation, and amplitudes of the ERN and Pe did not differ between groups. The MCQ-30 factors that measure cognitive confidence and positive beliefs about worry significantly predicted SPQ-BR total score, whereas ERPs did not. High self-reported schizotypy appears to be more associated with dysfunctional metacognitive beliefs than physiological abnormalities in brain areas related to metacognition. PMID- 26381183 TI - PBA regulates neurogenesis and cognition dysfunction after repeated electroconvulsive shock in a rat model. AB - Electroconvulsive therapy (ECT) was widely used to treat the refractory depression. But ECT led to the cognitive deficits plaguing the depression patients. The underlying mechanisms of the cognitive deficits remain elusive. Repeated electroconvulsive shock (rECS) was used to simulate ECT and explore the mechanisms of ECT during the animal studies. Previous studies showed rECS could lead to neurogenesis and cognitive impairment. But it was well known that neurogenesis could improve the cognition. So these suggested that the mechanism of the cognitive deficit after rECS was very complex. In present study, we explored the probable mechanisms of the cognitive deficit after rECS from neurogenesis aspect. We found the cognitive deficit was reversible and neurogenesis could bring a long-term beneficial effect on cognition. Astrogliosis and NR1 down-regulation probably participated in the reversible cognitive deficits after rECS. Phenylbutyric acid (PBA), generally as an agent to investigate the roles of histone acetylation, could prevent the reversible cognitive dysfunction, but PBA could diminish the long-term effect of enhanced cognition by rECS. These suggested that ECT could possibly bring the long-term beneficial cognitive effect by regulating neurogenesis. PMID- 26381184 TI - The impact of ecological momentary assessment on posttraumatic stress symptom trajectory. AB - Ecological momentary assessment includes continuous, real-time gathering of self report data in a participant's natural environment. The current study evaluated the possible impact of this assessment strategy on severity of posttraumatic stress (PTS) in a sample of participants who reported experiencing a past traumatic event. Participants with clinically elevated PTS symptoms reported symptom severity at three time-points: during an initial screening, following an unmonitored period, and following two weeks of monitoring. During the monitoring period, participants carried an Android device which prompted them to report PTS symptoms and negative emotions six times daily. PTS severity scores were then compared across these three time-points. Results indicated that participating in the ecological momentary assessment protocol was associated with a significant reduction in PTS severity, whereas significant changes were not noted over the unmonitored control condition. The authors conclude that ecological momentary assessment may have therapeutic value even when not combined with formal intervention, and it may be a useful tool for improving the efficiency of a stepped-care approach to treating PTS symptoms. PMID- 26381185 TI - Presence of anti-HBc is associated to high rates of HBV resolved infection and low threshold for Occult HBV Infection in HIV patients with negative HBsAg in Chile. AB - HBV-HIV coinfection is prevalent. Frequently, anti-HBc is the only serological marker of HBV, which can be indicative of HBV resolved infection, when found together with anti-HBs reactivity; or present as "isolated anti-HBc," related to HBV occult infection with presence of detectable DNA HBV, more prevalent in HIV positive individuals. Regional data about this condition are scarce. Anti-HBc rapid test has been used as screening, but its performance has not been described in HIV-positive patients. The aim of this study was determine prevalence of anti HBc in HIV-positive patients, serological pattern of HBV resolved infection and isolated anti-HBc, evaluating presence of HBV occult infection. Assess anti-HBc rapid test compared to ECLIA. Methods included measurement of anti-HBc and anti HBs in HIV-positive patients with negative HBsAg. Serum HBV DNA quantification and HBV booster vaccination to "isolated anti-HBc" individuals. Detection of anti HBc by rapid test and ECLIA. In 192 patients, prevalence of anti-HBc was 42.7% (82/192); associated to male gender, drug use, men-sex-men, positive-VDRL, and longer time HIV diagnosis. 34.4% (66/192) had presence of anti-HBs, mean titers of 637 ui/ml. Isolated anti-HBc in 8.3% (16/192), associated to detectable HIV viral load and no-use of HAART; in them, HBV DNA was undetectable, and 60% responded to HBV vaccination booster. Anti-HBc rapid test showed low sensibility (32.9%) compared to ECLIA. These results show that prevalence of anti-HBc in HIV positive individuals is high, in most cases accompanied with anti-HBs as HBV resolved infection. Low prevalence of "isolated anti-HBc," with undetectable HBV DNA, and most had anamnestic response to HBV vaccination; suggest low possibility of occult HBV infection. Anti-HBc rapid test cannot be recommended as screening method for anti-HBc. PMID- 26381187 TI - The Link that Lasts: A New Frontier in Supramolecular Block Copolymer Design. AB - Lasting link: A supramolecular linkage between two parts of an amphiphilic block copolymer was developed that is sufficiently strong to allow phase-separation driven nanopatterning as well as chromatographic characterization. The link can also be severed in response to a solvent trigger signal. This powerful approach will open new avenues for the production of self-healing materials, triggered release systems, and reversible surface designs. PMID- 26381186 TI - New TLR7 agonists with improved humoral and cellular immune responses. AB - Toll-like receptor 7 (TLR7) agonists are of interest as vaccine adjuvants and cancer therapeutics. Therefore, development of new TLR7 agonists that can efficiently promote host immune responses without evoking side effects is of great importance. Here, we describe two new compounds, J4 and F4, which elicit intracellular signaling exclusively via TLR7. Interestingly, both J4 and F4 induced less cytokine secretion (IL-1beta, IL-6, IL-10, IL-12p40, TNFalpha, and IL-12p70) from myeloid dendritic cells (mDCs) and monocytes than CL075 and R848; however, they all generated similar levels of phenotype maturation of antigen presenting cells (APCs), including plasmacytoid DCs. We further found that J4- and F4-induced APC activation was largely dependent on the activation of NF kappaB and p38. Lastly, J4 and F4 could efficiently promote B cell proliferation and plasmablast differentiation as well as antigen-specific CD8(+) T cell responses in human in vitro. Therefore, these new TLR7 agonists could be employed to facilitate the development of new therapeutics and vaccine adjuvants against cancers and microbial infections. PMID- 26381190 TI - Correction for Lo et al., Deletion of nfnAB in Thermoanaerobacterium saccharolyticum and Its Effect on Metabolism. PMID- 26381189 TI - Mapping Type IV Secretion Signals on the Primase Encoded by the Broad-Host-Range Plasmid R1162 (RSF1010). AB - The plasmid R1162 (RSF1010) encodes a primase essential for its replication. This primase makes up the C-terminal part of MobA, a multifunctional protein with the relaxase as a separate N-terminal domain. The primase is also translated separately as the protein RepB'. Here, we map two signals for type IV secretion onto the recently solved structure of RepB'. One signal is located internally within RepB' and consists of a long alpha-helix and an adjacent disordered region rich in arginines. The second signal is made up of the same alpha-helix and a second, arginine-rich region at the C-terminal end of the protein. Successive arginine-to-alanine substitutions revealed that either signal can be utilized by the type IV secretion complex of the plasmid R751. The internal signal also enables conjugal transfer when linked to the relaxase part of MobA. Both signals are similar to those previously identified for type IV secretion substrates in the Vir system of Agrobacterium tumefaciens. Moreover, the C-terminal arginine rich segment of RepB' has been shown to be secreted by Vir. However, with R751, the signals require MobB, an R1162-encoded accessory protein active in conjugal transfer. The results of two-hybrid assays revealed that MobB interacts, via its membrane-associated domain, with the R751 plasmid coupling protein TraG. In addition, MobB interacts with a region of MobA just outside the RepB' domain. Therefore, MobB is likely an adaptor that is essential for recognition of the primase-associated signals by the R751 secretion machinery. IMPORTANCE: For most plasmids, type IV secretion is an intrinsic part of the mechanism for conjugal transfer. Protein relaxases, bound to the 5' end of the transferring strand, are mobilized into recipient cells by the type IV pathway. In this work, we identify and characterize two signals for secretion in the primase domain of MobA, the relaxase of the IncQ plasmid R1162 (RSF1010). We also show that the adaptor protein MobB is required for engagement of these signals with the R751 coupling protein TraG. These results clarify the location and properties of secretion signals active during the conjugal transfer of plasmid DNA. PMID- 26381192 TI - Effects of robotic gait rehabilitation on biomechanical parameters in the chronic hemiplegic patients. AB - Hemiplegia is a more or less complete loss of hemibody voluntary motricity following a brain injury, usually resulting in alterations of the locomotor system with persistent disorders of movement and posture. We were interested in studying the gait pattern called "stiff knee gait" with the main objective to highlight the role of a robotic rehabilitation in improving or modifying/changing the walking pattern in adults with chronic hemiplegic disorders. Data were collected by a motion analysis system (Vicon((r))--Oxford Metrics, Oxford, UK) in order to achieve a Clinical Gait Analysis before and after a robotic gait rehabilitation (Lokomat((r))). Four intensive sessions per weeks during five weeks were performed by ten chronic hemiplegic adults. The results show a significant improvement in locomotor parameters (walking speed, step length, single and double support time) and in the knee kinematics. This first study provides experimental evidence of the importance and usefulness of the robotic rehabilitation as an aid in the rehabilitation of gait pattern in adults with chronic hemiplegia. PMID- 26381194 TI - Phosphoenolpyruvate carboxykinase (PEPCK) deficiency affects the germination, growth and fruit sugar content in tomato (Solanum lycopersicum L.). AB - Phosphoenolpyruvate carboxykinase (PEPCK) is a key regulatory enzyme and is utilized in the gluconeogenesis pathway in plants. Although, its catalytic and regulatory properties are quite well understood, there are uncertainties regarding its physiological role in many plants tissues such as the flesh of developing fruits. To further understand the function of PEPCK in fruits and other tissues, RNAi transgenic tomato plants in which SlPEPCK transcription was down-regulated by either CaMV 35S constitutive promoter or the fruit-specific E8 promoter were generated and characterized on the basis of their phenotypic and metabolic aspects. In the PEPCK-deficient lines, prominent growth suppression of germinated seedlings was observed and other vegetative suppression appeared during the early stage of plant growth in the 35S promoter-driven lines. In particular, root elongation was most obviously suppressed in the germinated seedlings, indicating that the gluconeogenesis pathway is involved in the root growth of seedlings. Regarding the primary metabolism in fruit, the soluble sugar content tended to decrease, whereas the malate content tended to increase in ripening fruits of the RNAi lines compared with the wild type. These results indicate that activation of the gluconeogenesis pathway from organic acids to sugars occurs during ripening but is suppressed by the knocking down of the PEPCK gene, suggesting that PEPCK participates in determining the sugar/acid ratio in ripening fruit. PMID- 26381193 TI - Declining and rebounding unhealthy alcohol consumption during the first year of HIV care in rural Uganda, using phosphatidylethanol to augment self-report. AB - AIMS: We examined whether unhealthy alcohol consumption, which negatively impacts HIV outcomes, changes after HIV care entry overall and by several factors. We also compared using phosphatidylethanol (PEth, an alcohol biomarker) to augment self-report to using self-report alone. DESIGN: A prospective 1-year observational cohort study with quarterly visits. SETTING: Large rural HIV clinic in Mbarara, Uganda. PARTICIPANTS: A total of 208 adults (89 women and 119 men) entering HIV care, reporting any prior year alcohol consumption. MEASUREMENTS: Unhealthy drinking was PEth+ (>= 50 ng/ml) or Alcohol Use Disorders Identification Test-Consumption+ (AUDIT-C+, over 3 months, women >= 3; men >= 4). We calculated adjusted odds ratios (AOR) for unhealthy drinking per month since baseline, and interactions of month since baseline with perceived health, number of HIV symptoms, antiretroviral therapy (ART), gender and self-reported prior unhealthy alcohol use. FINDINGS: The majority of participants (64%) were unhealthy drinkers (PEth+ or AUDIT-C+) at baseline. There was no significant trend in unhealthy drinking overall [per-month AOR: 1.01; 95% confidence interval (CI) = 0.94-1.07], while the per-month AORs were 0.91 (95% CI = 0.83-1.00) and 1.11 (95% CI = 1.01-1.22) when participants were not yet on ART and on ART, respectively (interaction P-value < 0.01). In contrast, 44% were AUDIT-C+; the per-month AORs for being AUDIT-C+ were 0.89 (95% CI = 0.85-0.95) overall, and 0.84 (95% CI = 0.78-0.91) and 0.97 (95% CI = 0.89-1.05) when participants were not on and were on ART, respectively. CONCLUSIONS: Unhealthy alcohol use among Ugandan adults entering HIV care declines prior to the start of anti-retroviral therapy but rebounds with time. Augmenting self-reported alcohol use with biomarkers increases the ability of current alcohol use measurements to detect unhealthy alcohol use. PMID- 26381195 TI - The toc132toc120 heterozygote mutant of Arabidopsis thaliana accumulates reduced levels of hexadecatrienoic acid. AB - A null and heterozygous mutant for the Arabidopsis thaliana TOC132 and TOC120 genes accumulates increased levels of 16:0 and decreased 16:3, suggesting altered homeostasis in fatty acid synthesis. The FAD5 gene encodes a plastid desaturase that catalyzes the first step in the synthesis of 16:3 in monogalactosyldiacylglycerol (MGDG). In non-acclimated toc132toc120+/- mutant plants, the FAD5 gene was repressed and this correlated with decreased levels of 16:3. In cold-acclimated mutant however, the FAD5 gene was upregulated and there was a small increase in 16:3 levels relative to the non-acclimated mutant plants. The MGD1 gene was expressed at control levels and the mutant accumulated levels of MGDG that were similar to the wild type. In the mutant however, MGDG had decreased 16:3 levels, suggesting that the activity of FAD5 desaturase was compromised. In the mutant, the FAD2 and FAD3 genes were downregulated but levels of 18:3-PC were increased, suggesting posttranscriptional regulation for the ER localized fatty acid desaturases. The Toc120 or Toc159 receptor is likely to compensate for a defective Toc132 receptor. In the cold-acclimated mutant, the TOC159 gene was repressed ca. 300-fold, whereas the TOC120 gene was repressed 7 fold relative to the non-acclimated wild type. Thus, the TOC159 gene is more sensitive to cold-stress and might not compensate for defect in the TOC132 gene under these conditions. Overall, these data show that a mutation in the TOC132 gene results in decreased 16:3 levels, indicating the need for an intact Toc132/Toc120 receptor, presumably to facilitate the import of the FAD5 preprotein into chloroplasts. PMID- 26381196 TI - Q-angle static or dynamic measurements, which is the best choice for patellofemoral pain? AB - BACKGROUND: The elevated Q-angle seems to be one of the most suggested factors contributing to patellofemoral pain. Females with patellofemoral pain are often evaluated through static clinical tests in clinical practice. However, the adaptations seem to appear more frequently in dynamic conditions. Performing static vs. dynamic evaluations of widely used measures would add to the knowledge in this area. Therefore, the aim of this study was to determine the reliability and discriminatory capability of three Q-angle measurements: a static clinical test, peak dynamic knee valgus during stair ascent and a static measurement using a three-dimensional system. METHOD: Twenty-nine females with patellofemoral pain and twenty-five pain-free females underwent clinical Q-angle measurement and static and dynamic knee valgus measurements during stair ascent, using a three dimensional system. All measurements were obtained and comparisons between groups, reliability and discriminatory capability were calculated. FINDINGS: Peak dynamic knee valgus was found to be greater in the patellofemoral pain group. On the other hand, no significant effects were found for static knee valgus or clinical Q-angle measurements between groups. The dynamic variable demonstrated the best discriminatory capability. Low values of reliability were found for clinical Q-angle, in contrast to the high values found for the three-dimensional system measurements. INTERPRETATION: Based on our findings, avoiding or correcting dynamic knee valgus during stair ascent may be an important component of rehabilitation programs in females with patellofemoral pain who demonstrate excessive dynamic knee valgus. Q-angle static measurements were not different between groups and presented poor values of discriminatory capability. PMID- 26381197 TI - Bronchogenic cyst: the rarest adrenal incidentaloma. PMID- 26381198 TI - Interest of the Ergo-Kit((r)) for the clinical practice of the occupational physician. A study of 149 patients recruited in a rehabilitation program. AB - OBJECTIVE: Functional capacity evaluation is commonly used to assess the abilities of patients to perform some tasks. Ergo-Kit((r)) is a validated tool assessing both functional capacities of patients and workplace demands. The objective of this study was to evaluate the relevance of the Ergo-Kit((r)) data for occupational physicians during the return-to-work process. METHODS: A retrospective and monocenter study was conducted on all patients included in a rehabilitation program and assessed with the Ergo-Kit((r)) tool between 2005 and 2014. Workplace demands and patients' functional capacities were evaluated and confronted. Self-beliefs and perceived disability were also assessed and compared to the functional capacity evaluation. RESULTS: One hundred and forty-nine working-age patients (85 men, 64 women; 39+/-12 years) suffering from musculoskeletal disorders or other diseases were included. Main causes of mismatch between workplace demands and functional capacities were manual handling of loads, postures with arms away from the body and repetitive motions at work; sitting posture was correlated with a lesser physical workload; and Oswestry score was correlated with functional capacities evaluated by the Ergo-Kit((r)). CONCLUSION: Ergo-Kit((r)) is a relevant tool to assess the multidimensional aspects of workplace demands and functional capacities. It could be very helpful for occupational physicians to manage return-to-work. PMID- 26381199 TI - [Disseminated tuberculosis in elderly patients]. PMID- 26381200 TI - A clinical approach to elimination of perinatal HIV transmission in resource-rich settings. PMID- 26381201 TI - Addition of growth hormone to the microflare stimulation protocol among women with poor ovarian response. AB - OBJECTIVE: To assess the efficacy of adding growth hormone (GH) to the microflare stimulation protocol among women with poor ovarian response. METHODS: A parallel, open-label, randomized controlled trial was conducted among patients with poor ovarian response who attended a center in Cairo, Egypt, between July 10 and December 31, 2014. Participants were randomly assigned using a computer program (random block size of 4-8) to undergo the microflare protocol with or without GH. Primary outcomes were the mean numbers of mature oocytes retrieved and fertilized. Analyses were done per protocol: women with cycle cancellations were excluded. RESULTS: The analysis included 72 women in the GH group and 73 in the microflare only group. The mean number of oocytes collected was 7.2+/-1.5 in the GH group versus 4.7+/-1.2 in the microflare only group (P<0.001). The mean number of metaphase II oocytes was 5.2+/-1.2 in the GH group and 2.8+/-1.0 in the microflare only group (P<0.001). The mean number of fertilized oocytes was higher in the GH group (4.2+/-1.1) than in the microflare only group (2.5+/-0.7; P<0.001). CONCLUSION: Addition of GH to the microflare stimulation protocol provided some potential benefits to women with poor ovarian response. However, further studies are required before it could be recommended for routine clinical use. ClinicalTrials.gov:NCT02185326. PMID- 26381202 TI - Quantitative proteomics reveals the central changes of wheat in response to powdery mildew. AB - Powdery mildew (Pm), caused by Blumeria graminis f. sp. tritici (Bgt), is one of the most important crop diseases, causing severe economic losses to wheat production worldwide. However, there are few reports about the proteomic response to Bgt infection in resistant wheat. Hence, quantitative proteomic analysis of N9134, a resistant wheat line, was performed to explore the molecular mechanism of wheat in defense against Bgt. Comparing the leaf proteins of Bgt-inoculated N9134 with that of mock-inoculated controls, a total of 2182 protein-species were quantified by iTRAQ at 24, 48 and 72h postinoculation (hpi) with Bgt, of which 394 showed differential accumulation. These differentially accumulated protein species (DAPs) mainly included pathogenesis-related (PR) polypeptides, oxidative stress responsive proteins and components involved in primary metabolic pathways. KEGG enrichment analysis showed that phenylpropanoid biosynthesis, phenylalanine metabolism and photosynthesis-antenna proteins were the key pathways in response to Bgt infection. InterProScan 5 and the Gibbs Motif Sampler cluster 394 DAPs into eight conserved motifs, which shared leucine repeats and histidine sites in the sequence motifs. Moreover, eight separate protein-protein interaction (PPI) networks were predicted from STRING database. This study provides a powerful platform for further exploration of the molecular mechanism underlying resistant wheat responding to Bgt. SIGNIFICANCE: Powdery mildew, caused by Blumeria graminis f. sp. tritici (Bgt), is a destructive pathogenic disease in wheat producing regions worldwide, resulting in severe yield reductions. Although many resistant wheat varieties have been cultivated, there are few reports about the proteomic response to Bgt infection in resistant wheat. Therefore, an iTRAQ-based quantitative proteomic analysis of a resistant wheat line (N9134) in response to Bgt infection has been performed. This paper provides new insights into the underlying molecular mechanism of wheat in response to Bgt. The proteomic analysis can significantly narrow the field of potential defense-related protein species, and is conducive to recognize the critical or effector protein under Bgt infection more precisely. Taken together, large amounts of high-throughput data provide a powerful platform for further exploration of the molecular mechanism on wheat-Bgt interactions. PMID- 26381203 TI - Quantitative proteogenomics of human pathogens using DIA-MS. AB - The increasing number of bacterial genomes in combination with reproducible quantitative proteome measurements provides new opportunities to explore how genetic differences modulate proteome composition and virulence. It is challenging to combine genome and proteome data as the underlying genome influences the proteome. We present a strategy to facilitate the integration of genome data from several genetically similar bacterial strains with data independent analysis mass spectrometry (DIA-MS) for rapid interrogation of the combined data sets. The strategy relies on the construction of a composite genome combining all genetic data in a compact format, which can accommodate the fusion with quantitative peptide and protein information determined via DIA-MS. We demonstrate the method by combining data sets from whole genome sequencing, shotgun MS and DIA-MS from 34 clinical isolates of Streptococcus pyogenes. The data structure allows for fast exploration of the data showing that undetected proteins are on average more amenable to amino acid substitution than expressed proteins. We identified several significantly differentially expressed proteins between invasive and non-invasive strains. The work underlines how integration of whole genome sequencing with accurately quantified proteomes can further advance the interpretation of the relationship between genomes, proteomes and virulence. This article is part of a Special Issue entitled: Computational Proteomics. PMID- 26381204 TI - mapDIA: Preprocessing and statistical analysis of quantitative proteomics data from data independent acquisition mass spectrometry. AB - Data independent acquisition (DIA) mass spectrometry is an emerging technique that offers more complete detection and quantification of peptides and proteins across multiple samples. DIA allows fragment-level quantification, which can be considered as repeated measurements of the abundance of the corresponding peptides and proteins in the downstream statistical analysis. However, few statistical approaches are available for aggregating these complex fragment-level data into peptide- or protein-level statistical summaries. In this work, we describe a software package, mapDIA, for statistical analysis of differential protein expression using DIA fragment-level intensities. The workflow consists of three major steps: intensity normalization, peptide/fragment selection, and statistical analysis. First, mapDIA offers normalization of fragment-level intensities by total intensity sums as well as a novel alternative normalization by local intensity sums in retention time space. Second, mapDIA removes outlier observations and selects peptides/fragments that preserve the major quantitative patterns across all samples for each protein. Last, using the selected fragments and peptides, mapDIA performs model-based statistical significance analysis of protein-level differential expression between specified groups of samples. Using a comprehensive set of simulation datasets, we show that mapDIA detects differentially expressed proteins with accurate control of the false discovery rates. We also describe the analysis procedure in detail using two recently published DIA datasets generated for 14-3-3beta dynamic interaction network and prostate cancer glycoproteome. AVAILABILITY: The software was written in C++ language and the source code is available for free through SourceForge website http://sourceforge.net/projects/mapdia/.This article is part of a Special Issue entitled: Computational Proteomics. PMID- 26381205 TI - Microbial community dynamics and biogas production from manure fractions in sludge bed anaerobic digestion. AB - AIMS: To elucidate how granular sludge inoculum and particle-rich organic loading affect the structure of the microbial communities and process performance in upflow anaerobic sludge bed (UASB) reactors. METHODS AND RESULTS: We investigated four reactors run on dairy manure filtrate and four on pig manure supernatant for three months achieving similar methane yields. The reactors fed with less particle rich pig manure stabilized faster and had highest capacity. Microbial community dynamics analysed by a PCR/denaturing gradient gel electrophoresis approach showed that influent was a major determinant for the composition of the reactor communities. Comparisons of pre- and non-adapted inoculum in the reactors run on pig manure supernatant showed that the community structure of the nonadapted inoculum adapted in approximately two months. Microbiota variance partitioning analysis revealed that running time, organic loading rate and inoculum together explained 26 and 31% of the variance in bacterial and archaeal communities respectively. CONCLUSIONS: The microbial communities of UASBs adapted to the reactor conditions in treatment of particle rich manure fractions, obtaining high capacity, especially on pig manure supernatant. SIGNIFICANCE AND IMPACT OF THE STUDY: These findings provide relevant insight into the microbial community dynamics in startup and operation of sludge bed reactors for methane production from slurry fractions, a major potential source of biogas. PMID- 26381206 TI - There's no place like biome: Can helminths restore the body's ecosystem? PMID- 26381207 TI - A multi-outcome analysis of the effects of treatment timing in the management of zygomatic fractures. AB - The aim of this study was to analyze the effects of surgical treatment delay in the management of zygomatic fractures. A retrospective case series of 99 patients was undertaken. Four outcome measures were analyzed in relation to delay: facial symmetry, facial scarring, trismus, and radiographic outcome. Five additional variables were subsequently analyzed: operation, diagnosis, primary operator, regular alcohol use, and regular cigarette use. Statistically significant associations were found between delay and facial scarring, and delay and radiographic outcome. For each additional delay of a day, the odds of facial scarring being present, compared to absent, decreased by 13% (odds ratio (OR) 0.87, 95% confidence interval (CI) 0.76-0.98). For regular cigarette users, for each additional day of delay there was a 306-fold increased risk of having a radiographic outcome of major deviation from premorbid compared to equivalent to premorbid (OR 306.38, 95% CI 2.08-45,161.49). For non-regular cigarette users/non users, for each additional day of delay there was a 1.5-fold increased risk of having a radiographic outcome of major deviation from premorbid compared to equivalent to premorbid (OR 1.50, 95% CI 1.08-2.09). These findings correlate with commonly held beliefs and anecdotal evidence. Despite the limitations, this study allows for an evidence-based approach to the timing of treatment of zygomatic fractures. PMID- 26381208 TI - Micro-computed tomography and histomorphometric analysis of human alveolar bone repair induced by laser phototherapy: a pilot study. AB - Immediate dental implant placement in the molar region is critical, because of the high amount of bone loss and the discrepancy between alveolar crest thickness and the implant platform. Laser phototherapy (LPT) improves bone repair. The aim of this study was to evaluate the human alveolar bone repair 40 days after molar extraction in patients submitted to LPT. Twenty patients were selected for this randomized controlled clinical trial; 10 underwent LPT (laser group) with a GaAlAs diode laser (808 nm, 100 mW, 0.04 cm(2), 75 J/cm(2), 30s per point, 3 J per point, at five points). The control group patients (n=10) were not irradiated. Forty days later, the tissue formed inside the sockets was analyzed by micro-computed tomography and histomorphometry. Data from the two groups were compared with Student's t-test and Pearson's correlation test. The relative bone volume was significantly higher in the laser group (P<0.0001). The control group showed negative correlations (P<0.01) between number and thickness, and between number and separation of trabeculae, and a positive correlation between thickness and separation of trabeculae. The laser group showed a significant negative correlation between the number and thickness of trabeculae (P<0.01). The results suggest that LPT is able to accelerate alveolar bone repair after molar extraction, leading to a more homogeneous trabecular configuration represented by thin and close trabeculae. PMID- 26381209 TI - Prenatal diagnosis of isolated coronary artery fistulas: progression and outcome in five cases. AB - OBJECTIVES: The aim of this study was to describe the clinical characteristics, progression, treatment, and outcomes in isolated coronary artery fistula cases diagnosed prenatally. METHODS: We carried out a retrospective review of babies diagnosed prenatally with coronary artery fistulas between January, 2000 and December, 2013; five fetuses were included. Echocardiographic features and measurements were noted during pregnancy and after birth. Treatment and outcome were noted. RESULTS: Gestational age at initial diagnosis was between 19 and 22 weeks; four coronary artery fistulas originated from the right and one from the left circumflex coronary artery. Drainage was into the right atrium in four cases and into the left ventricle in one case. There was cardiomegaly in two cases at the initial scan. The size of the fistulas increased during pregnancy in all except one. All prenatal diagnoses were confirmed postnatally. Among all, two patients developed congestive cardiac failure soon after birth and required transcatheter closure of the coronary artery fistula, 5 and 17 days after birth, respectively; three patients remained asymptomatic, and all of them showed progressive dilation of the feeding artery and had closure of the fistula at 20 months, 4 years, and 7 years of age, respectively. During the follow-up period, which ranged 2-14 years, all the patients were alive and well. CONCLUSIONS: Coronary artery fistulas can be diagnosed accurately during fetal life. Some babies may develop congestive cardiac failure soon after birth requiring early treatment. Those treated conservatively should be kept under review as intervention may be required later. PMID- 26381210 TI - Discovery of Inhibitors of Trypanosoma brucei by Phenotypic Screening of a Focused Protein Kinase Library. AB - A screen of a focused kinase inhibitor library against Trypanosoma brucei rhodesiense led to the identification of seven series, totaling 121 compounds, which showed >50 % inhibition at 5 MUm. Screening of these hits in a T. b. brucei proliferation assay highlighted three compounds with a 1H-imidazo[4,5-b]pyrazin 2(3H)-one scaffold that showed sub-micromolar activity and excellent selectivity against the MRC5 cell line. Subsequent rounds of optimisation led to the identification of compounds that exhibited good in vitro drug metabolism and pharmacokinetics (DMPK) properties, although in general this series suffered from poor solubility. A scaffold-hopping exercise led to the identification of a 1H pyrazolo[3,4-b]pyridine scaffold, which retained potency. A number of examples were assessed in a T. b. brucei growth assay, which could differentiate static and cidal action. Compounds from the 1H-imidazo[4,5-b]pyrazin-2(3H)-one series were found to be either static or growth-slowing and not cidal. Compounds with the 1H-pyrazolo[3,4-b]pyridine scaffold were found to be cidal and showed an unusual biphasic nature in this assay, suggesting they act by at least two mechanisms. PMID- 26381212 TI - A moment from before 365 Ma frozen in time and space. AB - This study presents a detailed analysis of an exceptionally well-preserved articulated specimen of the trilobite Trimerocephalus from the Late Devonian of the Holy Cross Mountains in Poland. X-ray microtomography reveals the oldest direct evidence for a moulting episode known from the fossil record. The process of moulting as well as associated features observed in the investigated specimen are interpreted by comparison with extinct and extant Xiphosurida arthropods, which survived global P/T extinction and are among the closest extant relatives of trilobites. A very special moment frozen in time and space millions years ago provides rare insights into the behavior and physiology of these long-extinct arthropods. PMID- 26381211 TI - Experimental hookworm infection and escalating gluten challenges are associated with increased microbial richness in celiac subjects. AB - The intestinal microbiota plays a critical role in the development of the immune system. Recent investigations have highlighted the potential of helminth therapy for treating a range of inflammatory disorders, including celiac disease (CeD); however, the mechanisms by which helminths modulate the immune response of the human host and ameliorate CeD pathology are unknown. In this study, we investigated the potential role of alterations in the human gut microbiota in helminth-mediated suppression of an inflammatory disease. We assessed the qualitative and quantitative changes in the microbiota of human volunteers with CeD prior to and following infection with human hookworms, and following challenge with escalating doses of dietary gluten. Experimental hookworm infection of the trial subjects resulted in maintenance of the composition of the intestinal flora, even after a moderate gluten challenge. Notably, we observed a significant increase in microbial species richness over the course of the trial, which could represent a potential mechanism by which hookworms can regulate gluten-induced inflammation and maintain intestinal immune homeostasis. PMID- 26381213 TI - Small angle X-ray scattering studies of CTNNBL1 dimerization and CTNNBL1/CDC5L complex. AB - The hPrp19/CDC5L complex is a non-snRNP spliceosome complex that plays a key role in the spliceosome activation during pre-mRNA splicing, and CTNNBL1 and CDC5L are essential components of the complex. In this study, to investigate the oligomeric state of CTNNBL1 in solution, we performed small angle X-ray scattering experiments in various concentrations of NaCl. We observed that CTNNBL1 existed as a dimer in physiological NaCl concentrations. Site-directed mutagenesis experiment of CTNNBL1 confirmed that N-terminal capping region and the first four ARM repeats are important for dimerization of the protein. We also found that the positively-charged NLS3-containing region (residues 197-235) of CDC5L bound to the negatively-charged patch of CTNNBL1 and that the CTNNBL1/CDC5L complex formed a heterotetramer consisting of one CTNNBL1 dimer and one CDC5L dimer. Moreover, reconstruction of 3D models of CTNNBL1/CDC5L complexes containing CTNNBL1 and three different truncated forms of CDC5L showed that the CDC5L(141-196) region and the CDC5L(236-377) region were positioned at the top of the N-terminal capping region and at the bottom of ARM VII of CTNNBL1, respectively. PMID- 26381215 TI - Depression Worsening Associated With Lorcaserin: A Case Report. PMID- 26381214 TI - Regulation of NKT cell-mediated immune responses to tumours and liver inflammation by mitochondrial PGAM5-Drp1 signalling. AB - The receptor-interacting protein kinase 3 (RIPK3) plays crucial roles in programmed necrosis and innate inflammatory responses. However, a little is known about the involvement of RIPK3 in NKT cell-mediated immune responses. Here, we demonstrate that RIPK3 plays an essential role in NKT cell function via activation of the mitochondrial phosphatase phosphoglycerate mutase 5 (PGAM5). RIPK3-mediated activation of PGAM5 promotes the expression of cytokines by facilitating nuclear translocation of NFAT and dephosphorylation of dynamin related protein 1 (Drp1), a GTPase is essential for mitochondrial homoeostasis. Ripk3(-/-) mice show reduced NKT cell responses to metastatic tumour cells, and both deletion of RIPK3 and pharmacological inhibition of Drp1 protects mice from NKT cell-mediated induction of acute liver damage. Collectively, the results identify a crucial role for RIPK3-PGAM5-Drp1/NFAT signalling in NKT cell activation, and further suggest that RIPK3-PGAM5 signalling may mediate crosstalk between mitochondrial function and immune signalling. PMID- 26381216 TI - Patient characteristics and outcomes of carotid endarterectomy and carotid artery stenting: analysis of the German mandatory national quality assurance registry - 2003 to 2014. AB - AIM: In Germany, every surgical or endovascular procedure on the extracranial carotid artery is documented in a mandatory quality assurance registry. The purpose of this study is to describe the patient characteristics, the indications for treatment, and the short-term outcomes as well as to analyse the corresponding trends from 2003 to 2014. METHODS: Data on demographics, peri procedural measures, and outcomes were extracted from the annual quality reports published by the Federal Agency for Quality Assurance and the Institute for Applied Quality Improvement and Research in Health Care. Data were available from 2003 to 2014 for carotid endarterectomy (CEA) and from 2012 to 2014 for carotid artery stenting (CAS). The primary outcome event of this study is any stroke or death until discharge from hospital. Temporal trends of categorical variables were statistically analysed using the Cochran-Armitage test for trend. RESULTS: Between 2003 and 2014, 309,405 CEAs and 18,047 CAS procedures were documented in the database; 68.1% of all patients were male. The mean age of patients treated with CEA increased from 68.9 years in 2003 to 70.9 years in 2014. The proportion of patients with ASA stages III to V increased from 65% to 71% in CEA, whereas it decreased from 44% to 41% in CAS patients. 53.1% of all CEAs were performed for asymptomatic patients (group A), 34.4% for symptomatic patients treated electively (group B), and 11.2% a in a collective group including other indications for CEA or CAS (such as recurrent stenosis, carotid aneurysms, emergency treatment due to stroke-in-evolution). The corresponding data for CAS are 49.3%, 26.1% and 26.3% respectively. In group B, the interval between the neurological index event and CEA decreased from 28 to 8 days (P<0.001). In patients treated with CAS, this interval was 9 days in 2012 (no further data available). On average, 67.1% and 48.2% of surgically treated patients as well as 77.8% and 69.8% of CAS patients were neurologically assessed before and after the procedure, respectively. From 2003 to 2014, CEA procedures were performed more frequently in locoregional anesthesia (10.1% to 29.1%, P<0.001). The same trend was observed for the application of the eversion technique (37.0% to 41.6%, P<0.001), the neurophysiological monitoring (49.8% to 61.8%, P<0.001), and the intra-procedural assessment of the treated artery (44.5% to 69.7%, P<0.001). In contrast, shunting was used less frequently (48.1% to 43.0%, P<0.001). Averagely 95.7% of all endovascular procedures were performed using stent-angioplasty. In 54.2% a protection device was used. Nitinol and bare metal stents were used in 74.1% and 21.4% of cases, respectively. The in-hospital rate of any stroke or death decreased from 2.0% to 1.1% in asymptomatic patients treated with CEA without a contralateral stenosis >=75% or occlusion, P<0.001). In patients treated with CAS this rate did not increase (1.7% to 1.8%, p=0.909). The corresponding rates in CEA and CAS patients with severe contralateral stenosis or occlusion varied between 1.9%-3.1% and 2.2%-2.6%, respectively. In symptomatic patients (group B) with a stenosis of 50 percent or more, the rate of any stroke or death decreased significantly after CEA from 4.2% to 2.4% (P<0.001) and remained stable after CAS (3.9% to 3.5%, P=0.577). CONCLUSION: This report on 327,452 carotid procedures analysed one of the largest quality registries on CEA and CAS worldwide. Data indicate that treated patients became older and sicker, whereas in contrast, the in-hospital rates of stroke or death are decreasing over time. PMID- 26381217 TI - The social well-being of nurses shows a thirst for a holistic support: A qualitative study. AB - INTRODUCTION: Social well-being is one of the important aspects of health. In fact, this is a reflection of experience in a social environment, indicating how social challenges are determined. In other words, social well-being is an explanation of people's perception and experience of being in a good situation, satisfaction with the structure, and social interaction. This qualitative study intended to explore nurses' experience of social well-being. METHODS: Qualitative content analysis was used to conduct the study. Through purposive sampling, a total of 18 nurses with various clinical experiences participated in semi structured interviews. The data were analysed using the five-step, qualitative content analysis introduced by Graneheim and Lundman. RESULTS: The main theme extracted from the data analysis was "thirst for a holistic support" in nurses. It consisted of two subthemes including internal support (family's support, colleague's support, and organizational support) and external support (society's support and media's support). CONCLUSIONS AND DISCUSSION: Nurses' experiences in shaping their social well-being show that nurses need support in order to rebuild their social well-being. It is supported in partnership with the media, the community, health-related organizations, and by nurses and family. This improves job satisfaction, hope, motivation, commitment, and confidence so as to ultimately facilitate improvement of social well-being of nurses. PMID- 26381218 TI - Adeno-associated virus-2-mediated TGF-beta1 microRNA transfection inhibits adhesion formation after digital flexor tendon injury. AB - Adhesion formation after digital flexor tendon injury greatly affects gliding function of the tendon, which is a major clinical complication after hand surgery. Transforming growth factor beta 1 (TGF-beta1) has a critical role in adhesion formation during tendon healing. Persistent regulation of TGF-beta1 through application of microRNA (miRNA) specifically inhibiting the function of TGF-beta1 (TGF-beta1-miRNA) holds promise for treatment of such a complication. Adeno-associated virus (AAV) was used to transfer TGF-beta1-miRNA to the chicken digital flexor tendons, which had been injured and surgically repaired. Four doses of AAV2-TGF-beta1-miRNA (2 * 1011, 2 * 1010, 2 * 109 and 2 * 108 vector genomes (vg)) were used to determine the transfection efficiency. At postoperative 3 weeks, we found a positive correlation between the administered AAV2-TGF-beta1-miRNA doses and transfection efficiency. The transfection rate ranged from 10% to 77% as the doses increased. Production of TGF-beta1 protein in the tendons decreased on increasing vector dosage. When 2 * 1011 and 2 * 1010) vg were injected into the tendon, gliding excursion of the repaired tendon and work of flexion of chicken toes were significantly increased and adhesion score decreased 6 and 8 weeks later, indicating the improvement of tendon gliding and decreases in adhesion formations. However, the ultimate strength of the tendons transfected at the dose of 2 * 1010 vg was 12-24% lower than that of the control tendons. The results of this study demonstrate that application of TGF-beta1 miRNA had a mixed impact on tendon healing: adhesion around the tendon is reduced but strength of the tendon healing is adversely affected. Future studies should aim at maintaining the beneficial effects of reducing tendon adhesions, while eliminating the adverse effects of decreasing the healing strength. PMID- 26381219 TI - A bifurcated molecular pentad capable of sequential electronic energy transfer and intramolecular charge transfer. AB - An extended molecular array, comprising three distinct types of chromophores and two additional redox-active subunits, that harvests photons over most of the visible spectral range has been synthesized and characterised. The array exhibits a rich variety of electrochemical waves when examined by cyclic voltammetry but assignment can be made on the basis of control compounds and molecular orbital calculations. Stepwise electronic energy transfer occurs along the molecular axis, corresponding to a gradient of excitation energies, to populate the lowest energy excited state of the ultimate acceptor. The latter species, which absorbs and emits in the far-red region, enters into light-induced charge transfer with a terminal amine group. The array is relatively stable under illumination with white light but degrades slowly via a series of well-defined steps, the first of which is autocatalytic. One of the main attributes of this system is the capability to harvest an unusually high fraction of sunlight while providing protection against exposure to UV light. PMID- 26381220 TI - Fluid displacement during droplet formation at microfluidic flow-focusing junctions. AB - Microdroplets and microcapsules have been widely produced using microfluidic flow focusing junctions for biomedical and chemical applications. However, the multiphase microfluidic flow at the flow-focusing junction has not been well investigated. In this study, the displacement of two (core and shell) aqueous fluids that disperse into droplets altogether in a carrier oil emulsion was investigated both numerically and experimentally. It was found that extensive displacement of the two aqueous fluids within the droplet during its formation could occur as a result of the shear effect of the carrier fluid and the capillary effect of interfacial tension. We further identified that the two mechanisms of fluid displacement can be evaluated by two dimensionless parameters. The quantitative relationship between the degree of fluid displacement and these two dimensionless parameters was determined experimentally. Finally, we demonstrated that the degree of fluid displacement could be controlled to generate hydrogel microparticles of different morphologies using planar or nonplanar flow-focusing junctions. These findings should provide useful guidance to the microfluidic production of microscale droplets or capsules for various biomedical and chemical applications. PMID- 26381221 TI - A Mobile Internet Service for Self-Management of Physical Activity in People With Rheumatoid Arthritis: Challenges in Advancing the Co-Design Process During the Requirements Specification Phase. AB - BACKGROUND: User involvement in the development of health care services is important for the viability, usability, and effectiveness of services. This study reports on the second step of the co-design process. OBJECTIVE: The aim was to explore the significant challenges in advancing the co-design process during the requirements specification phase of a mobile Internet service for the self management of physical activity (PA) in rheumatoid arthritis (RA). METHODS: A participatory action research design was used to involve lead users and stakeholders as co-designers. Lead users (n=5), a clinical physiotherapist (n=1), researchers (n=2) with knowledge in PA in RA and behavioral learning theories, an eHealth strategist (n=1), and an officer from the patient organization (n=1) collaborated in 4 workshops. Data-collection methods included video recordings and naturalistic observations. RESULTS: The inductive qualitative video-based analysis resulted in 1 overarching theme, merging perspectives, and 2 subthemes reflecting different aspects of merging: (1) finding a common starting point and (2) deciding on design solutions. Seven categories illustrated the specific challenges: reaching shared understanding of goals, clarifying and handling the complexity of participants' roles, clarifying terminology related to system development, establishing the rationale for features, negotiating features, transforming ideas into concrete features, and participants' alignment with the agreed goal and task. CONCLUSIONS: Co-designing the system requirements of a mobile Internet service including multiple stakeholders was a complex and extensive collaborative decision-making process. Considering, valuing, counterbalancing, and integrating different perspectives into agreements and solutions (ie, the merging of participants' perspectives) were crucial for moving the process forward and were considered the core challenges of co-design. Further research is needed to replicate the results and to increase knowledge on key factors for a successful co-design of health care services. PMID- 26381222 TI - Dereplication of natural products using minimal NMR data inputs. AB - A strategy for the dereplication of a complete or a partial structure using (1)H NMR, (1)H-(13)C HSQC and (1)H-(1)H COSY spectral data, a molecular formula composition range and structural fragments against a massive database of about 22 million compounds is considered. As the increasing availability of public online databases containing natural products continues to grow the potential of utilizing these resources for dereplication purposes increases. This work examines approaches for NMR dereplication of natural products and includes a comparison with approaches for molecular formula and mass-based dereplication. The strategy is an application of computer-assisted structure elucidation using ACD/Structure Elucidator and data obtained from the ChemSpider database hosted by the Royal Society of Chemistry. PMID- 26381223 TI - Palladium-Catalyzed Decarboxylative Ortho-Ethoxycarbonylation of O-Methyl Ketoximes and 2-Arylpyridines with Potassium Oxalate Monoester. AB - A novel method for introducing an ester group via palladium-catalyzed ligand directed C-H activation has been explored. The ortho-ethoxycarbonylation of O methyl ketoximes proceeded smoothly with the nontoxic and easily handled reagent potassium oxalate monoester, affording the desired products in moderate to good yields. Furthermore, pyridine could also be employed as a directing group to obtain similar results in this transformation. PMID- 26381224 TI - Tuning Surface Charge and Morphology for the Efficient Detection of Dopamine under the Interferences of Uric Acid, Ascorbic Acid, and Protein Adsorption. AB - In this research, we aimed to evaluate the impact of the surface charges and morphologies of electrodes on electrochemically detecting dopamine (DA) in the presence of protein adsorption, uric acid (UA), and ascorbic acid (AA). Through the electropolymerization of functionalized 3,4-ethylenedioxythiophenes (EDOT) directly on Au electrodes, we successfully created PEDOT-coated electrodes with three different functional groups and nanostructures. Negatively charged carboxylic acid groups attracted DA while reducing the interferences of UA and AA due to electrostatic effect. We used charge-free tetra(ethylene glycol) and zwitterionic phosphocholine groups are used to evaluate the interference of protein adsorption on DA sensing because they both can effectively prevent the nonspecific adsorption of proteins. These two electrodes can avoid protein adsorption, yet proved ineffective for DA sensing: both tetra(ethylene glycol) and the phosphocholine groups are electroneutral and have minimal electrostatic interactions with DA. We also used three proteins of different isoelectric points - bovine serum albumin, lysozyme, and fibrinogen - to evaluate the influence of protein adsorption on DA detection. We found that for an electrode coated with carboxylic acid-functionalized PEDOT, the adsorption of positively charged lysozyme can promote the detection sensitivity of AA and UA, and that all protein adsorption lowers the sensitivity of DA. In contrast, nanostructures promote the detection sensitivity of all three molecules. All of our tested functionalized PEDOT-coated electrodes demonstrated good stability and functionality in buffers. PMID- 26381225 TI - Structural flexibilities and gas adsorption properties of one-dimensional copper(II) polymers with paddle-wheel units by modification of benzoate ligands. AB - CO2 and N2 gas adsorption/desorption properties of one-dimensional copper(II) polymers with paddle-wheel units [Cu(II)2(p-XBA)4(pyrazine)]infinity were successfully controlled through the tuning of interchain interactions by modification of para-substituent X groups on the benzoate (BA) ligands (X = Cl, Br, I, and OCH3). Although none of the four crystals had sufficient void space to integrate the crystallization solvents, gate-opening gas adsorption and desorption behaviors coupled with structural phase transitions were observed for CO2 (T = 195 K) and N2 (T = 77 K), with differences depending on the precise substituent. van der Waals interchain interactions, specifically pi...pi, halogen...pi, and C-H...pi contacts, were dominant in forming the crystal lattice; their magnitude was associated with gate-opening pressure and hysteresis behaviors. Both the type and magnitude of the interactions were evaluated by Hirshfeld surface analysis, which indicated that structural flexibility decreased as larger halogen atoms were included. Overall, weak interchain interaction and structural flexibility generated new void spaces to adsorb CO2 and N2 gases. PMID- 26381226 TI - Assessing the Potential for the Reactions of Epoxides with Amines on Secondary Organic Aerosol Particles. AB - Nuclear magnetic resonance techniques were used to study the kinetics and products of the reaction of a variety of epoxides with various amines under varying pH conditions. In agreement with a previous finding, the amine-epoxide reactions were found to be water-catalyzed and not directly dependent on the pH of the reaction environment. At pH values higher than the pK(a) of the particular amine, the amine-epoxide reactions were extremely efficient, outcompeting hydrolysis reactions even for conditions where water was the solvent and the amine was a relatively low-concentration solute. This finding was rationalized by measurements that showed that the relative nucleophilic strength of amines relative to water was on the order of 1000, while the nucleophilic strength of protonated amines (which are predominant when pH < pK(a)) was negligible. The epoxide carbon substitution environment was found to have a large effect on the measured rate constants (more substituted epoxides had slower rate constants), while the amine carbon substitution environment had a much more limited effect. While the amine-epoxide rate constants are large enough such that amine-epoxide reactions may be kinetically feasible for isoprene-derived epoxides and high amine secondary organic aerosol (SOA) concentrations, most atmospheric amines are expected to be present in protonated form on the largely acidic SOA found in the atmosphere and thus are expected to be largely unreactive toward epoxides. PMID- 26381227 TI - Fabrication of One-Dimensional Zigzag [6,6]-Phenyl-C61-Butyric Acid Methyl Ester Nanoribbons from Two-Dimensional Nanosheets. AB - One-dimensional (1D) zigzag [6,6]-phenyl-C61-butyric acid methyl ester (PCBM) nanoribbons are produced by folding two-dimensional ultrathin PCBM nanosheets in a simple solvent process. The unique 1D PCBM nanostructures exhibit uniform width of 3.8 +/- 0.3 nm, equivalent to four PCBM molecules, and lengths of 20-400 nm. These nanoribbons show well-defined crystalline structure, comprising PCBM molecules in a hexagonal arrangement without trapped solvent molecules. First principle calculations and detailed experimental characterization provide an insight into the structure and formation mechanism of the 1D PCBM nanoribbons. Given their dimensions and physical properties, we foresee that these nanostructures should be ideal as acceptor material in organic solar cells. PMID- 26381228 TI - A New Class of Thioredoxin-Related Protein Able to Bind Iron-Sulfur Clusters. AB - AIMS: Members of the thioredoxin (Trx) protein family participate mainly in redox pathways and have not been associated with Fe/S binding, in contrast to some closely related glutaredoxins (Grxs). Cestode parasites possess an unusual diversity of Trxs and Trx-related proteins with unexplored functions. In this study, we addressed the biochemical characterization of a new class of Trx related protein (IsTRP) and a classical monothiol Grx (EgGrx5) from the human pathogen Echinococcus granulosus. RESULTS: The dimeric form of IsTRP coordinates Fe2S2 in a glutathione-independent manner; instead, Fe/S binding relies on the CXXC motif conserved among Trxs. This novel binding mechanism allows holo-IsTRP to be highly resistant to oxidation. IsTRP lacks canonical reductase activities. Mitochondrially targeted IsTRP aids growth of a Grx5 null yeast strain. Similar complementation assays performed with EgGrx5 revealed functional conservation for class II Grxs, despite the presence of nonconserved structural elements. IsTRP is a cestode lineage-specific protein highly expressed in the gravid adult worm, which releases the infective stage critical for dissemination. INNOVATION: IsTRP is the first member from the Trx family to be reported to bind Fe/S. We disclose a novel mechanism of Fe/S coordination within the Trx folding unit, which renders the cluster highly resistant to oxidation-mediated disassembly. CONCLUSION: We demonstrate that IsTRP defines a new protein family within the Trx superfamily, confirm the conservation of function for class II Grx from nonphylogenetically related species, and highlight the versatility of the Trx folding unit to acquire Fe/S binding as a recurrent emergent function. Antioxid. Redox Signal. 00, 000 000. PMID- 26381229 TI - A Randomized Trial of 12-Week Interventions for the Treatment of Developmental Phonological Disorder in Francophone Children. AB - PURPOSE: This study was designed to test the relative efficacy of different combinations of intervention approaches when targeting speech production accuracy and phonological awareness skills. All children received individual speech therapy, a home program, and a small-group phonological awareness intervention. METHOD: Sixty-five 4-year-olds with a developmental phonological disorder received these intervention components in different combinations over 12 weeks, resulting in 4 groups: output-oriented individual intervention and articulation practice home program, output-oriented individual intervention and dialogic reading home program, input-oriented individual intervention and articulation practice home program, and input-oriented individual intervention and dialogic reading home program. RESULTS: A significant interaction of the individual treatment condition and the home program condition was observed for 2 outcome measures: targeted feature match (which reflected changes in speech production accuracy for features and word shape structures that were targeted in therapy) and explicit phonological awareness skills. CONCLUSION: In this context, in which the children received a brief period of direct therapy and a home program component provided sequentially, the most effective strategy was to teach the parents to use treatment procedures at home that were congruent with the direct therapy component. PMID- 26381230 TI - Potential role of gut microbiota and tissue barriers in Parkinson's disease and amyotrophic lateral sclerosis. AB - Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS) are neurodegenerative diseases with pathophysiology that may be related to the gastrointestinal tract. It is well established that tissue barriers maintain homeostasis and health. Furthermore, gut microbiota may have an impact on brain activity through the gut-microbiota-brain axis under both physiological and pathological conditions. In this review, we highlight the current knowledge regarding the role of gut microbiota and tissue barriers in PD and ALS. To our knowledge, this is the first review of the key issues involving both the altered gut microbiota and impaired tissue barriers in the pathophysiology of PD and ALS. PMID- 26381231 TI - Vitamin D status of psychiatric inpatients at a community teaching hospital in the Midwest. AB - BACKGROUND: Vitamin D deficiency is a re-emerging epidemic in North America. It is increasingly linked to the pathology of cognition and mental illness and is also common in psychiatric patients. AIMS: This study was designed to determine the prevalence of vitamin D deficiency among psychiatric inpatients in Kansas City, to explore the association between vitamin D status and clinical characteristics, and to identify the association of medical problems related to vitamin D deficiency in mental illness. METHODS: In this descriptive study we recruited 52 psychiatric inpatients at a community teaching hospital in Kansas City between August and November 2013. A vitamin D-deficient state was defined as serum 25-hydroxyvitamin D (25-(OH) D) level <= 20 ng/mL. In addition to descriptive statistics, the Student t-test and Pearson test were used in the study. RESULTS: A total of 15 patients (28.8%) were classified as deficient, 20 patients (38.5%) had an insufficiency, 17 patients (32.7%) were categorized as sufficient. Interestingly, there was a statistically significant difference in 25 (OH) D levels between African Americans and Caucasians (t = -2.216, p = 0.03) but no significant relationship between 25-(OH) D level and gender, major psychiatric diagnoses, type 2 diabetes mellitus or obesity. There was also no correlation between 25-(OH) D level and age, body mass index or haemoglobin A1C. CONCLUSIONS: Low 25-(OH) D level was found in a high percentage of psychiatric inpatients in Kansas City. Screening for vitamin D deficiency could be a routine work-up for psychiatric inpatients. Vitamin D supplement for African American inpatients with low vitamin D levels could be considered. PMID- 26381232 TI - Immunity and clinical efficacy of an inactivated enterovirus 71 vaccine in healthy Chinese children: a report of further observations. AB - BACKGROUND: To investigate the long-term effects on immunity of an inactivated enterovirus 71 (EV71) vaccine and its protective efficacy. METHODS: A sub-cohort of 1,100 volunteers from Guangxi Province in China was eligible for enrolment and randomly administered either the EV71 vaccine or a placebo on days 0 and 28 in a phase III clinical trial and then observed for the following 2 years with approval by an independent ethics committee of Guangxi Zhuang Autonomous Region, China. Serum samples from the 350 participants who provided a full series of blood samples (at all the sampling points) within the 2-year period were collected. Vaccine-induced immune effects, including the neutralizing antibody titres and cross-protection against different genotypes of EV71, were examined. This study also evaluated the protective efficacy of this vaccine based upon clinical diagnosis. RESULTS: This sub-cohort showed a >60% drop-out rate over 2 years. The seroconversion rates among the 161 immunized subjects remained >95% at the end of study. The geometric mean titres of neutralizing antibodies (anti genotype C4) 360 days after vaccination in 350 subjects were 81.0 (subjects aged 6-11 months), 98.4 (12-23 months), 95.0 (24-35 months), and 81.8 (36-71 months). These titres subsequently increased to 423.1, 659.0, 545.0, and 321.9, respectively, at 540 days post-immunization (d.p.i.), and similar levels were maintained at 720 d.p.i. Higher IFN-gamma/IL-4-specific responses to the C4 genotype of EV71 and cross-neutralization reactivity against major EV71 genotype strains were observed in the vaccine group compared to those in the placebo group. Five EV71-infected subjects were observed in the placebo-treated control group and none in the vaccine-immunized group in per-protocol analysis. CONCLUSION: These results are consistent with the induction of dynamic immune responses and protective efficacy of the vaccine against most circulating EV71 strains. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov, NCT01569581, Trial registration date: March 2012. PMID- 26381233 TI - Socioeconomic gradients in the effects of universal school-based health behaviour interventions: a systematic review of intervention studies. AB - BACKGROUND: Socioeconomic inequalities in health behaviour emerge in early life before tracking into adulthood. Many interventions to improve childhood health behaviours are delivered via schools, often targeting poorer areas. However, targeted approaches may fail to address inequalities within more affluent schools. Little is known about types of universal school-based interventions which make inequalities better or worse. METHODS: Seven databases were searched using a range of natural language phrases, to identify trials and quasi experimental evaluations of universal school-based interventions focused on smoking, alcohol, diet and/or physical activity, published from 2008-14. Articles which examined differential effects by socioeconomic status (N = 20) were synthesised using harvest plot methodology. Content analysis of 98 intervention studies examined potential reasons for attention or inattention to effects on inequality. RESULTS: Searches identified approximately 12,000 hits. Ninety-eight evaluations were identified, including 90 completed studies, of which 20 reported effects on SES inequality. There were substantial geographical biases in reporting of inequality, with only 1 of 23 completed North American studies testing differential effects, compared to 15 out of 52 completed European studies. Studies reported a range of positive, neutral or negative SES gradients in effects. All studies with a negative gradient in effect (i.e. which widened inequality) included educational components alone or in combination with environmental change or family involvement. All studies with positive gradients in effects included environmental change components, alone or combined with education. Effects of multi-level interventions on inequality were inconsistent. Content analyses indicated that in approximately 1 in 4 studies SES inequalities were discussed in defining the problem or rationale for intervention. Other potential barriers to testing effect on inequality included assumptions that universal delivery guaranteed universal effect, or that interventions would work better for poorer groups because they had most to gain. CONCLUSIONS: Universal school-based interventions may narrow, widen or have no effect on inequality. There is a significant need for more routine testing of the effects of such interventions on inequality to enable firmer conclusions regarding types of interventions which affect inequality. PROSPERO REGISTRATION NUMBER: CRD42014014548. PMID- 26381234 TI - Prospective sonographic detection of spina bifida at 11-14 weeks and systematic literature review. AB - OBJECTIVE: To conduct a literature review to assess the effectiveness of first trimester ultrasonographic markers of spina bifida (SB) integrating data with our prospective experience. METHODS: The analysis of the SB cases that we prospectively detected in the first trimester, between January 2012 and February 2014, and a systematic review of all the papers evaluating the effectiveness of SB ultrasonographic markers at 11-14 weeks, namely brain stem diameter (BS), fourth ventricle/intracranial translucency (IT), cisterna magna (CM), brain stem/occipital bone distance (BSOB), the ratio between BS and BSOB. Some studies assess only the effectiveness of IT, others include more parameters, and few include them all. RESULTS: We prospectively detected four SB cases, three open (OSB) and one closed (CSB), in a low risk population undergoing first trimester screening. In the three OSB, CM (in 2/3 cases) and BSOB (3/3) distance were below the 5th percentile, BS and BS/BSOB ratio (3/3) were above the 95th percentile. In the CSB, all the measurements were within normal limits. CONCLUSION: The literature and our data agree that most fetuses with OSB demonstrate in the first trimester positive sonographic markers in the posterior fossa, but additional prospective studies are needed to establish the best protocol for OSB screening. PMID- 26381235 TI - An ensemble approach to accurately detect somatic mutations using SomaticSeq. AB - SomaticSeq is an accurate somatic mutation detection pipeline implementing a stochastic boosting algorithm to produce highly accurate somatic mutation calls for both single nucleotide variants and small insertions and deletions. The workflow currently incorporates five state-of-the-art somatic mutation callers, and extracts over 70 individual genomic and sequencing features for each candidate site. A training set is provided to an adaptively boosted decision tree learner to create a classifier for predicting mutation statuses. We validate our results with both synthetic and real data. We report that SomaticSeq is able to achieve better overall accuracy than any individual tool incorporated. PMID- 26381236 TI - Zero-profile implant versus conventional cage-plate implant in anterior cervical discectomy and fusion for the treatment of degenerative cervical spondylosis: a meta-analysis. AB - BACKGROUND: Zero-profile implant has become more and more popular in anterior cervical discectomy and fusion (ACDF) for the treatment of degenerative cervical spondylosis. However, there was no enough evidence judging its efficiency and safety. The aim of this analysis was to evaluate the efficacy and safety of Zero profile implant compared with conventional cage-plate (CCP) in ACDF. METHODS: All studies directly comparing the outcomes between the Zero-profile implant and CCP implant in ACDF were included, and the search strategy followed the requirements of the Cochrane Library Handbook. Two of the authors extracted relevant data and checked the accuracy independently using standardized data collection form. RESULTS: Seven studies involving 560 patients were included, 262 in the Zero profile group and 298 in the CCP group. Zero-profile implant had a lower rate of postoperative dysphagia at 2 weeks, 6 months, and 1 year (p = 0.0002, p = 0.008, and p = 0.001, respectively) than CCP implant. Zero-profile also reduced blood loss (p = 0.0001), while operation time and incidence of postoperative transient dysphagia had no statistical significance (p = 0.92, p = 0.42, respectively) between two groups. CONCLUSION: Based on the results of our analysis, the application of Zero-profile implant in ACDF had a lower rate of postoperative dysphagia at 2 weeks, 6 months, and 1 year than CCP implant. Zero-profile implant also had fewer blood loss during operation. More rigorous and adequately powered prospective randomized controlled trials with larger sample size are required to elucidate a more objective outcome. PMID- 26381238 TI - Deploying aptameric sensing technology for rapid pandemic monitoring. AB - The genome of virulent strains may possess the ability to mutate by means of antigenic shift and/or antigenic drift as well as being resistant to antibiotics with time. The outbreak and spread of these virulent diseases including avian influenza (H1N1), severe acute respiratory syndrome (SARS-Corona virus), cholera (Vibrio cholera), tuberculosis (Mycobacterium tuberculosis), Ebola hemorrhagic fever (Ebola Virus) and AIDS (HIV-1) necessitate urgent attention to develop diagnostic protocols and assays for rapid detection and screening. Rapid and accurate detection of first cases with certainty will contribute significantly in preventing disease transmission and escalation to pandemic levels. As a result, there is a need to develop technologies that can meet the heavy demand of an all embedded, inexpensive, specific and fast biosensing for the detection and screening of pathogens in active or latent forms to offer quick diagnosis and early treatments in order to avoid disease aggravation and unnecessary late treatment costs. Nucleic acid aptamers are short, single-stranded RNA or DNA sequences that can selectively bind to specific cellular and biomolecular targets. Aptamers, as new-age bioaffinity probes, have the necessary biophysical characteristics for improved pathogen detection. This article seeks to review global pandemic situations in relation to advances in pathogen detection systems. It particularly discusses aptameric biosensing and establishes application opportunities for effective pandemic monitoring. Insights into the application of continuous polymeric supports as the synthetic base for aptamer coupling to provide the needed convective mass transport for rapid screening is also presented. PMID- 26381237 TI - Potent Chemopreventive/Antioxidant Activity Detected in Common Spices of the Apiaceae Family. AB - Spices are used worldwide, particularly in the Asian and Middle Eastern countries, and considered protective against degenerative diseases, including cancer. Here, we report the efficacy of aqueous and non-aqueous extracts of 11 Apiaceae spices for free radical-scavenging activity and to inhibit cytochrome P450s in two separate reactions involving: 1) 4-hydroxy-17beta-estradiol (4E2), DNA, and CuCl2 and 2) 17beta-estradiol, rat liver microsomes, cofactors, DNA and CuCl2. Oxidative DNA adducts resulting from redox cycling of 4E2 were analyzed by (32)P-postlabeling. Aqueous (5 mg/ml) and non-aqueous extracts (6 mg/ml) substantially inhibited (83-98%) formation of DNA adducts in the microsomal reaction. However, in nonmicrosomal reaction, only aqueous extracts showed the inhibitory activity (83-96%). Adduct inhibition was also observed at five-fold lower concentrations of aqueous extracts of cumin (60%) and caraway (90%), and 10 fold lower concentrations of carrot seeds (76%) and ajowan (90%). These results suggests the presence of 2 groups of phytochemicals: polar compounds that have free radical-scavenging activity and lipophilic compounds that selectively inhibit P450 activity associated with estrogen metabolism. Because most of these Apiaceae spices are used widely with no known toxicity, the phytochemicals from the Apiaceae spices used in foods may be potentially protective against estrogen mediated breast cancer. PMID- 26381239 TI - Sentinel node biopsy using indocyanine green in oral/oropharyngeal cancer. AB - BACKGROUNDS: Radioactive tracer-based detection has been proposed as a standard procedure in identifying sentinel nodes for cN0 oral/oropharyngeal carcinoma. However, access to radioactive isotopes may be limited in some surgical centers, and there is potential risk of the radioactive tracers to the operators. This study was designed to evaluate the feasibility of near-infrared fluorescence imaging with indocyanine green combined with blue dye mapping in sentinel node biopsy for cN0 oral/oropharyngeal carcinoma. METHODS: Twenty-six cases of previously untreated oral/oropharyngeal carcinoma staged cT1-2N0M0 were enrolled in this study. One milliliter of indocyanine green (5 mg/ml) and 1.5 ml of methylene blue (1 mg/ml) were injected sequentially around the primary tumor in a four-quadrant pattern before skin incision. After elevation of the platysma flap and posterior retraction of the sternocleidomastoid muscle, fluorescence images were taken with a near-infrared detector, with special attention paid to any blue dyed lymph nodes. Lymph nodes identified first with fluorescent hot spots with or without blue dye were defined as sentinel nodes, and they were harvested and sent for pathologic study. RESULTS: Sentinel nodes were successfully harvested in all 26 cases. The number of sentinel nodes (SNs) per case varied from 1 to 9, with an average of 3.4. Routine pathology demonstrated occult metastasis exclusively in SNs in four cases (15.4 %). No tracer-associated side effects occurred in this series. CONCLUSIONS: Near-infrared imaging using indocyanine green combined with methylene blue mapping is a feasible and reliable new method for SN biopsy in cN0 oral/oropharyngeal carcinoma. PMID- 26381240 TI - Timing of shoot development transitions affects degree of perenniality in Arabidopsis lyrata (Brassicaceae). AB - BACKGROUND: Perenniality is best understood in quantitative terms, involving the relationship between production vs. turnover of meristems, biomass, or energy reserves. Previous quantitative trait locus (QTL) studies using divergent populations of the perennial rock cress Arabidopsis lyrata have shown that trade offs in vegetative growth vs. reproduction are due to cascading effects of differences in early vegetative development, which contribute to local adaptation. However, details of the developmental differences and how they affect perenniality remained unclear. In this study, we investigated in detail the developmental differences in perenniality between populations. A. lyrata from Norway and North Carolina populations, representing contrasting environments and degrees of perenniality, were grown under controlled conditions, and data were collected on plant phenology and shoot-level development. We tested hypotheses that differences in perenniality involve strict allocation of lateral meristems to vegetative vs. reproductive fates, or alternatively quantitative effects of pre-reproductive vegetative development. RESULTS: The two populations showed large differences in the degree of vegetative development on individual shoots prior to reproductive transitions. The number of leaves produced on shoots prior to bolting, and not strict meristem allocation or variation in apical dominance, was able to explain variation in the number of inflorescences on individual plants. These results suggested that allocation of time to shoot vegetative vs. reproductive development could be a major factor in resource allocation differences between the populations. CONCLUSIONS: Based on these results and those of previous QTL studies, we propose a model in which the degree of shoot vegetative development shapes the developmental context for reproduction and subsequent vegetative growth in different environments. Climate-specific effects of shoot development patterns on reproductive output and survival may result in divergent evolutionary trajectories along a perenniality continuum, which may have broader relevance for plant life history evolution. PMID- 26381241 TI - Protein-protein interactions between SWCNT/chitosan/EGF and EGF receptor: a model of drug delivery system. AB - Epidermal growth factor (EGF) was used as the targeting ligand to enhance the specificity of a cancer drug delivery system (DDS) via its specific interaction with the EGF receptor (EGFR) that is overexpressed on the surface of some cancer cells. To investigate the intermolecular interaction and binding affinity between the EGF-conjugated DDS and the EGFR, 50 ns molecular dynamics simulations were performed on the complex of tethered EGFR and EGF linked to single-wall carbon nanotube (SWCNT) through a biopolymer chitosan wrapping the tube outer surface (EGFR.EGF-CS-SWCNT-Drug complex), and compared to the EGFR.EGF complex and free EGFR. The binding pattern of the EGF-CS-SWCNT-Drug complex to the EGFR was broadly comparable to that for EGF, but the binding affinity of the EGF-CS-SWCNT Drug complex was predicted to be somewhat better than that for EGF alone. Additionally, the chitosan chain could prevent undesired interactions of SWCNT at the binding pocket region. Therefore, EGF connected to SWCNT via a chitosan linker is a seemingly good formulation for developing a smart DDS served as part of an alternative cancer therapy. PMID- 26381242 TI - Baseline susceptibility to alpha-cypermethrin in Lutzomyia longipalpis (Lutz & Neiva, 1912) from Lapinha Cave (Brazil). AB - BACKGROUND: Given the increase in cases of visceral leishmaniasis in recent years, associated with the socio-economic impact of this disease, as well as the wide distribution of Lutzomyia longipalpis in Brazil and the likelihood that this vector may develop resistance to insecticides used for control, the Ministry of Health considers as crucial the creation of a network in order to study and monitor the resistance of this vector to insecticides used for control. In this sense, this study aimed: 1) to characterize the susceptibility of L. longipalpis from Lapinha Cave (Lagoa Santa, MG - Brazil) to Alfateck SC200 in field bioassays, and 2) to define the susceptibility baseline to alpha-cypermethrin in laboratory bioassays, checking the possibility of using it as susceptibility reference lineage (SRL). FINDINGS: The field bioassays revealed that the tested population was highly susceptible to alpha-cypermethrin in all time periods with high mortality (~100 %) in all treated surfaces before six months after spraying. In the laboratory bioassays, the studied population presented LD50, LD95 and LD99 to 0.78013, 10.5580 and 31.067 mg/m(2), respectively. The slope was 1.454121. CONCLUSIONS: The studied population of L. longipalpis was considered as adequate for SRL according criterion recommended by Pan-American Health Organization and has proven susceptibility to tested insecticide in the field. One cannot rule out the possibility of finding populations of L. longipalpis more susceptible to alpha-cypermethrin; therefore, further research is necessary on other populations with potential use as a SRL. PMID- 26381243 TI - Sequence-Defined Energetic Shifts Control the Disassembly Kinetics and Microstructure of Amelogenin Adsorbed onto Hydroxyapatite (100). AB - The interactions between proteins and surfaces are critical to a number of important processes including biomineralization, the biocompatibility of biomaterials, and the function of biosensors. Although many proteins exist as monomers or small oligomers, amelogenin is a unique protein that self-assembles into supramolecular structures called "nanospheres," aggregates of hundreds of monomers that are 20-60 nm in diameter. The nanosphere quaternary structure is observed in solution; however, the quaternary structure of amelogenin adsorbed onto hydroxyapatite (HAP) surfaces is not known even though it may be important to amelogenin's function in forming highly elongated and intricately assembled HAP crystallites during enamel formation. We report studies of the interactions of the enamel protein, amelogenin (rpM179), with a well-defined (100) face prepared by the synthesis of large crystals of HAP. High-resolution in situ atomic force microscopy (AFM) was used to directly observe protein adsorption onto HAP at the molecular level within an aqueous solution environment. Our study shows that the amelogenin nanospheres disassemble onto the HAP surface, breaking down into oligomeric (25-mer) subunits of the larger nanosphere. In some cases, the disassembly event is directly observed by in situ imaging for the first time. Quantification of the adsorbate amounts by size analysis led to the determination of a protein binding energy (17.1k(b)T) to a specific face of HAP (100). The kinetics of disassembly are greatly slowed in aged solutions, indicating that there are time-dependent increases in oligomer-oligomer binding interactions within the nanosphere. A small change in the sequence of amelogenin by the attachment of a histidine tag to the N-terminus of rpM179 to form rp(H)M180 results in the adsorption of a complete second layer on top of the underlying first layer. Our research elucidates how supramolecular protein structures interact and break down at surfaces and how small changes in the primary sequence of amelogenin can affect the disassembly process. PMID- 26381244 TI - DNAzyme-based therapeutics for cancer treatment. AB - Gene-silencing strategies based on catalytic nucleic acids have been rapidly developed in the past decades. Ribozymes, antisense oligonucleotides and RNA interference have been actively pursued for years due to their potential application in gene inactivation. Pioneered by Joyce et al., a new class of catalytic nucleic acid composed of deoxyribonucleotides has emerged via an in vitro selection system. The therapeutic potential of these RNA-cleaving DNAzymes have been shown both in vitro and in vivo. Although they rival the activity and stability of synthetic ribozymes, they are limited by inefficient delivery to the intracellular targets. Recent successes in clinical testing of the DNAzymes in cancer patients have revitalized the potential clinical utility of DNAzymes. PMID- 26381245 TI - Topical application of propolis enhances cutaneous wound healing by promoting TGF beta/Smad-mediated collagen production in a streptozotocin-induced type I diabetic mouse model. AB - BACKGROUND/AIMS: Impaired wound healing is considered to be one of the most serious complications associated with diabetes as it significantly increases the susceptibility of patients to infection. Propolis is a natural bee product used extensively in foods and beverages that has significant benefits to human health. In particular, propolis has antioxidant, anti-inflammatory and analgesic effects that could be useful for improving wound healing. In this study, we investigated the effects of topical application of propolis on the healing and closure of diabetic wounds in a streptozotocin (STZ)-induced type I diabetic mouse model. METHODS: Sixty male mice were distributed equally into 3 experimental groups: group 1, non-diabetic control mice; group 2, diabetic mice; and group 3, diabetic mice treated daily with a topical application of propolis. RESULTS: We found that diabetic mice exhibited delayed wound closure characterized by a significant decrease in the levels of TGF-beta1 and a prolonged elevation of the levels of inflammatory cytokines (IL-1beta, IL-6 and TNF-alpha) and MMP9 in wound tissues compared with control non-diabetic mice. Moreover, the wound tissues of diabetic mice showed a marked reduction in the phosphorylation of Smad2 and Smad3 as well as a marked reduction in collagen production. Interestingly, compared with untreated diabetic mice, topical application of propolis significantly enhanced the closure of diabetic wounds and decreased the levels of IL-1beta, IL-6, TNF alpha and MMP9 to near normal levels. Most importantly, compared with untreated diabetic mice, the treatment of diabetic mice with propolis significantly enhanced the production of collagen via the TGF-beta1/Smad2,3 signaling axis in wounded tissues. CONCLUSION: Our findings reveal the molecular mechanisms underlying the improved healing and closure of diabetic wounds following topical propolis application. PMID- 26381246 TI - Assessment of image-derived risk factors for natural course of unruptured cerebral aneurysms. AB - OBJECTIVE: The goal of this prospective longitudinal study was to test whether image-derived metrics can differentiate unruptured aneurysms that will become unstable (grow and/or rupture) from those that will remain stable. METHODS: One hundred seventy-eight patients harboring 198 unruptured cerebral aneurysms for whom clinical observation and follow-up with imaging surveillance was recommended at 4 clinical centers were prospectively recruited into this study. Imaging data (predominantly CT angiography) at initial presentation was recorded. Computational geometry was used to estimate numerous metrics of aneurysm morphology that described the size and shape of the aneurysm. The nonlinear, finite element method was used to estimate uniform pressure-induced peak wall tension. Computational fluid dynamics was used to estimate blood flow metrics. The median follow-up period was 645 days. Longitudinal outcome data on these aneurysm patients-whether their aneurysms grew or ruptured (the unstable group) or remained unchanged (the stable group)-was documented based on follow-up at 4 years after the beginning of recruitment. RESULTS: Twenty aneurysms (10.1%) grew, but none ruptured. One hundred forty-nine aneurysms (75.3%) remained stable and 29 (14.6%) were lost to follow-up. None of the metrics-including aneurysm size, nonsphericity index, peak wall tension, and low shear stress area-differentiated the stable from unstable groups with statistical significance. CONCLUSIONS: The findings in this highly selected group do not support the hypothesis that image derived metrics can predict aneurysm growth in patients who have been selected for observation and imaging surveillance. If aneurysm shape is a significant determinant of invasive versus expectant management, selection bias is a key limitation of this study. PMID- 26381247 TI - Therapeutic temperature modulation in severe or moderate traumatic brain injury: a propensity score analysis of data from the Nationwide Japan Neurotrauma Data Bank. AB - OBJECTIVE: In patients with severe traumatic brain injury (TBI), a randomized controlled trial revealed that outcomes did not significantly improve after therapeutic hypothermia (TH) or normothermia (TN). However, avoiding pyrexia, which is often associated with intracranial disorders, might improve clinical outcomes. The objective of this study was to compare neurological outcomes among patients with moderate and severe TBI after therapeutic temperature modulation (TTM) in the absence of other interventions. METHODS: Data from 1091 patients were obtained from the Japan Neurotrauma Data Bank Project 2009, a cohort observational study. Patients with cardiac arrest, those with a Glasgow Coma Scale score of 3 and dilated fixed pupils, and those whose cause of death was injury to another area of the body were excluded, leaving 687 patients aged 16 years or older in this study. The patients were divided into 2 groups: the TTM group underwent TN (213 patients) or TH (82 patients), and the control group (392 patients) did not receive TTM. The primary end point for this study was the rate of poor outcome at hospital discharge, and the secondary end point was in hospital death. Out of the 208 total items in the database, 29 variables that could potentially affect outcome were matched using the propensity score (PS) method in order to reduce selection bias and balance the baseline characteristics. RESULTS: From each group, 141 patients were extracted using the PS-matching process. Among the patients in the TTM group, 29 had undergone TH and 112 had undergone TN. In a log-rank test using Kaplan-Meier survival curves, no significant differences in patient outcome or death were observed between the 2 groups (poor outcome, p = 0.83; death, p = 0.18). A Cox proportional-hazards regression analysis established the HR for poor outcome and mortality at 1.03 (95% CI 0.78-1.36, p = 0.83) and 1.34 (95% CI 0.87-2.07, p = 0.18), respectively. CONCLUSIONS: There was no clear improvement in neurological outcomes after TTM in patients with moderate or severe TBI. To elucidate the role of TTM in patients with these injuries, a prospective study is needed with long-term follow-up using specific target temperatures. PMID- 26381249 TI - Editorial: Rupture risk of unruptured aneurysms: beyond size and shape. PMID- 26381248 TI - Reconsidering the logic of World Federation of Neurosurgical Societies grading in patients with severe subarachnoid hemorrhage. AB - OBJECTIVE: Current data show a favorable outcome in up to 50% of patients with World Federation of Neurosurgical Societies (WFNS) Grade V subarachnoid hemorrhage (SAH) and a rather poor prediction of worst cases. Thus, the usefulness of the current WFNS grading system for identifying the worst scenarios for clinical studies and for making treatment decisions is limited. One reason for this lack of differentiation is the use of "negative" or "silent" diagnostic signs as part of the WFNS Grade V definition. The authors therefore reevaluated the WFNS scale by using "positive" clinical signs and the logic of the Glasgow Coma Scale as a progressive herniation score. METHODS: The authors performed a retrospective analysis of 182 patients with SAH who had poor grades on the WFNS scale. Patients were graded according to the original WFNS scale and additionally according to a modified classification, the WFNS herniation (hWFNS) scale (Grade IV, no clinical signs of herniation; Grade V, clinical signs of herniation). The prediction of poor outcome was compared between these two grading systems. RESULTS: The positive predictive values of Grade V for poor outcome were 74.3% (OR 3.79, 95% CI 1.94-7.54) for WFNS Grade V and 85.7% (OR 8.27, 95% CI 3.78 19.47) for hWFNS Grade V. With respect to mortality, the positive predictive values were 68.3% (OR 3.9, 95% CI 2.01-7.69) for WFNS Grade V and 77.9% (OR 6.22, 95% CI 3.07-13.14) for hWFNS Grade V. CONCLUSIONS: Limiting WFNS Grade V to the positive clinical signs of the Glasgow Coma Scale such as flexion, extension, and pupillary abnormalities instead of including "no motor response" increases the prediction of mortality and poor outcome in patients with severe SAH. PMID- 26381250 TI - Use of fat-suppressed T2 -weighted sagittal images after infusion of excess saline into the subarachnoid space as a new diagnostic modality for cerebrospinal fluid hypovolemia: technical note. AB - The diagnosis of CSF hypovolemia remains controversial. The primary diagnostic factor relies on confirmation of leakage of the CSF based on reduced spinal fluid pressure. Determining the specific leakage site is the most important issue for effective treatment but remains a difficult task. Although CT myelography, radioisotope cisternography, and MRI are commonly performed in the diagnosis of CSF hypovolemia, these techniques can rarely identify the precise leakage site. Therefore, an epidural blood patch is performed in the lumbar spine in many cases. This study reports a new diagnostic modality that can help to confirm the leakage site. Fat-suppressed T2-weighted sagittal images were compared before and after the infusion of 20 ml of saline into the subarachnoid space of the lumbar region to detect the specific leakage site with high probability. Three patients were successfully treated by the epidural blood patch based on data obtained with the new diagnostic modality. Two patients were treated in the cervical region and 1 in the lumbar region. The use of fat-suppressed T2-weighted sagittal images after saline infusion could be a relevant diagnostic modality compared with images obtained by CT myelography, radioisotope cisternography, and ordinary MRI to achieve accurate diagnosis and effective treatment of patients with CSF hypovolemia. PMID- 26381251 TI - Unruptured intracranial aneurysm treatment effects on cognitive function: a meta analysis. AB - OBJECTIVE: The treatment of an unruptured intracranial aneurysm (UIA) is not free of morbidity and mortality, and the decision is made by weighing the risks of treatment complications against the risk of aneurysm rupture. This meta-analysis quantitatively analyzed the literature on the effects of UIA treatment on cognition. METHODS: MEDLINE, Embase, and PsycInfo were systematically searched for studies that reported on the cognitive status of UIA patients before and after aneurysm treatment. The search was restricted to prospective cohort and case-control studies published between January 1, 1998, and January 1, 2013. The analyses focused on the effect of treatment on general cognitive functioning, with an emphasis on 4 specific cognitive domains: executive functions, verbal and visual memory, and visuospatial functions. RESULTS: Eight studies, with a total of 281 patients, were included in the meta-analysis. Treatment did not affect general cognitive functioning (effect size [ES] -0.22 [95% CI -0.78 to 0.34]). Executive functions and verbal memory domains trended toward posttreatment impairment (ES -0.46 [95% CI -0.93 to 0.01] and ES -0.31 [95% CI -1.24 to 0.61]), and performance of visual memory tasks trended toward posttreatment improvement (ES 1.48 [95% CI -0.36 to 3.31]). Lastly, treatment did not significantly affect visuospatial functions (ES -0.08 [95% CI -0.30 to 0.45]). CONCLUSIONS: The treatment of an UIA does not seem to affect long-term cognitive function. However, definitive conclusions were not possible due to the paucity of studies addressing this issue. PMID- 26381252 TI - Cavitation-enhanced nonthermal ablation in deep brain targets: feasibility in a large animal model. AB - OBJECT Transcranial MRI-guided focused ultrasound (TcMRgFUS) is an emerging noninvasive alternative to surgery and radiosurgery that is undergoing testing for tumor ablation and functional neurosurgery. The method is currently limited to central brain targets due to skull heating and other factors. An alternative ablative approach combines very low intensity ultrasound bursts and an intravenously administered microbubble agent to locally destroy the vasculature. The objective of this work was to investigate whether it is feasible to use this approach at deep brain targets near the skull base in nonhuman primates. METHODS In 4 rhesus macaques, targets near the skull base were ablated using a clinical TcMRgFUS system operating at 220 kHz. Low-duty-cycle ultrasound exposures (sonications) were applied for 5 minutes in conjunction with the ultrasound contrast agent Definity, which was administered as a bolus injection or continuous infusion. The acoustic power level was set to be near the inertial cavitation threshold, which was measured using passive monitoring of the acoustic emissions. The resulting tissue effects were investigated with MRI and with histological analysis performed 3 hours to 1 week after sonication. RESULTS Thirteen targets were sonicated in regions next to the optic tract in the 4 animals. Inertial cavitation, indicated by broadband acoustic emissions, occurred at acoustic pressure amplitudes ranging from 340 to 540 kPa. MRI analysis suggested that the lesions had a central region containing red blood cell extravasations that was surrounded by edema. Blood-brain barrier disruption was observed on contrast-enhanced MRI in the lesions and in a surrounding region corresponding to the prefocal area of the FUS system. In histology, lesions consisting of tissue undergoing ischemic necrosis were found in all regions that were sonicated above the inertial cavitation threshold. Tissue damage in prefocal areas was found in several cases, suggesting that in those cases the sonication exceeded the inertial cavitation threshold in the beam path. CONCLUSIONS It is feasible to use a clinical TcMRgFUS system to ablate skull base targets in nonhuman primates at time-averaged acoustic power levels at least 2 orders of magnitude below what is needed for thermal ablation with this device. The results point to the risks associated with the method if the exposure levels are not carefully controlled to avoid inertial cavitation in the acoustic beam path. If methods can be developed to provide this control, this nonthermal approach could greatly expand the use of TcMRgFUS for precisely targeted ablation to locations across the entire brain. PMID- 26381253 TI - Safety and efficacy of aneurysm treatment with WEB: results of the WEBCAST study. AB - OBJECT WEB is an innovative intrasaccular treatment for intracranial aneurysms. Preliminary series have shown good safety and efficacy. The WEB Clinical Assessment of Intrasaccular Aneurysm Therapy (WEBCAST) trial is a prospective European trial evaluating the safety and efficacy of WEB in wide-neck bifurcation aneurysms. METHODS Patients with wide-neck bifurcation aneurysms for which WEB treatment was indicated were included in this multicentergood clinical practices study. Clinical data including adverse events and clinical status at 1 and 6 months were collected and independently analyzed by a medical monitor. Six-month follow-up digital subtraction angiography was also performed and independently analyzed by a core laboratory. Success was defined at 6 months as complete occlusion or stable neck remnant, no worsening in angiographic appearance from postprocedure, and no retreatment performed or planned. RESULTS Ten European neurointerventional centers enrolled 51 patients with 51 aneurysms. Treatment with WEB was achieved in 48 of 51 aneurysms (94.1%). Adjunctive implants (coils/stents) were used in 4 of 48 aneurysms (8.3%). Thromboembolic events were observed in 9 of 51 patients (17.6%), resulting in a permanent deficit (modified Rankin Scale [mRS] Score 1) in 1 patient (2.0%). Intraoperative rupture was not observed. Morbidity (mRS score > 2) and mortality were 2.0% (1 of 51 patients, related to rupture status on entry to study) and 0.0% at 1 month, respectively. Success was achieved at 6 months in 85.4% of patients treated with WEB: 23 of 41 patients (56.1%) had complete occlusion, 12 of 41 (29.3%) had a neck remnant, and 6 of 41 (14.6%) had an aneurysm remnant. CONCLUSIONS The WEBCAST study showed good procedural and short-term safety of aneurysm treatment with WEB and good 6 month anatomical results. PMID- 26381254 TI - Safety, efficacy, and life satisfaction following epilepsy surgery in patients aged 60 years and older. AB - OBJECTIVE: Despite its potential to offer seizure freedom, resective epilepsy surgery (RES) is seldom performed in patients 60 years of age or older. Demonstrating successful outcomes including an improved quality of life may raise awareness about the advantages of referring this underrepresented population for specialized evaluation. Accordingly, the authors investigated outcomes and life fulfillment in patients with an age >= 60 years who had undergone RES. METHODS: All patients who, at the age of 60 years or older, had undergone RES for medically refractory focal onset seizures at the authors' center were evaluated. A modified Liverpool Life Fulfillment (LLF) tool was administered postoperatively (maximum score 32). Seizure outcomes were classified according to the Engel classification system. RESULTS: Twelve patients underwent RES. The majority of patients (9 [75%] of 12) had at least 1 medical comorbidity in addition to seizures. The mean follow-up was 3.1 +/- 2.1 years. At the time of the final follow-up, 11 (91.7%) of 12 patients were documented as having a good postsurgical outcome (Engel Class I-II). Half (6 of 12 patients) were completely seizure free (Engel Class IA). Liverpool Life Fulfillment (LLF) data were available for 11 patients. Following surgery, the mean LLF score was 26.7 +/- 6. Eight patients (72.7%) noted excellent satisfaction with their RES, with 5 (45.5%) noting postoperative improvements in overall health. CONCLUSIONS: Resective epilepsy surgery is safe and effective in patients with an age >= 60 years. Over 90% had a good surgical outcome, with 50% becoming completely seizure free despite 1 or more medical comorbidities in the majority. The study data indicated that an advancing age should not negatively influence consideration for RES. PMID- 26381255 TI - Endoplasmic reticulum stress implicated in chronic traumatic encephalopathy. AB - OBJECTIVE: Chronic traumatic encephalopathy is a progressive neurodegenerative disease characterized by neurofibrillary tau tangles following repetitive neurotrauma. The underlying mechanism linking traumatic brain injury to chronic traumatic encephalopathy has not been elucidated. The authors investigate the role of endoplasmic reticulum stress as a link between acute neurotrauma and chronic neurodegeneration. METHODS: The authors used pharmacological, biochemical, and behavioral tools to assess the role of endoplasmic reticulum stress in linking acute repetitive traumatic brain injury to the development of chronic neurodegeneration. Data from the authors' clinically relevant and validated rodent blast model were compared with those obtained from postmortem human chronic traumatic encephalopathy specimens from a National Football League player and World Wrestling Entertainment wrestler. RESULTS: The results demonstrated strong correlation of endoplasmic reticulum stress activation with subsequent tau hyperphosphorylation. Various endoplasmic reticulum stress markers were increased in human chronic traumatic encephalopathy specimens, and the endoplasmic reticulum stress response was associated with an increase in the tau kinase, glycogen synthase kinase-3beta. Docosahexaenoic acid, an endoplasmic reticulum stress inhibitor, improved cognitive performance in the rat model 3 weeks after repetitive blast exposure. The data showed that docosahexaenoic acid administration substantially reduced tau hyperphosphorylation (t = 4.111, p < 0.05), improved cognition (t = 6.532, p < 0.001), and inhibited C/EBP homology protein activation (t = 5.631, p < 0.01). Additionally the data showed, for the first time, that endoplasmic reticulum stress is involved in the pathophysiology of chronic traumatic encephalopathy. CONCLUSIONS: Docosahexaenoic acid therefore warrants further investigation as a potential therapeutic agent for the prevention of chronic traumatic encephalopathy. PMID- 26381256 TI - Letter to the Editor: Transfalcine approach. PMID- 26381257 TI - Microembolism after endovascular coiling of unruptured cerebral aneurysms: incidence and risk factors. AB - OBJECTIVE: The incidence and risk factors of microembolic lesions on MR diffusion weighted imaging (DWI) were analyzed after the endovascular coiling of unruptured intracranial aneurysms (UIAs). METHODS: Data obtained from 271 consecutive patients (70 men and 201 women; median age 57 years; range 23-79 years) who presented with UIA for coil embolization between July 2011 and June 2013 were analyzed. Two independent reviewers examined the DWI and apparent diffusion coefficient maps obtained the following day for the presence of restrictive diffusion spots and counted the number of spots. Multivariate analysis was then performed to identify independent risk factors for developing microembolism following the coiling of an aneurysm. RESULTS: Microembolic lesions were noted in 101 of 271 patients (37.3%). The results of the multivariate analysis showed that the following factors significantly influenced the risk for microembolism: age, diabetes, previous history of ischemic stroke, high-signal FLAIR lesions in the white matter, multiple aneurysms, and the insertion of an Enterprise stent (all ORs > 1.0 and all p values < 0.05). Previously known risk factors such as prolonged procedure duration, aneurysm size, and decreased antiplatelet function did not show any significant influence. CONCLUSIONS: The incidence of microembolism after endovascular coiling of UIA was not low. Lesions occurred more frequently in patients with vascular status associated with old age, diabetes, and previous stroke. Aneurysm multiplicity and the type of stent used for treatment also influenced lesion occurrence. PMID- 26381258 TI - Editorial: Subarachnoid hemorrhage grading scales. PMID- 26381259 TI - Germline CDKN2A mutations in childhood melanoma: a case of melanoma-pancreatic cancer syndrome. PMID- 26381260 TI - A systematic review of implant outcomes in treated periodontitis patients. AB - OBJECTIVES: To investigate the effect of treated periodontitis on implant outcomes in partially edentulous individuals compared with periodontally healthy patients. MATERIAL AND METHODS: Longitudinal studies reporting on implant survival, success, incidence of peri-implantitis, bone loss and periodontal status, and on partially dentate patients with a history of treated periodontitis were included. RESULTS: The search yielded 14,917 citations. Twenty-seven publications met the inclusion criteria for qualitative data synthesis. Implant success and survival were higher in periodontally healthy patients, whilst bone loss and incidence of peri-implantitis was increased in patients with history of treated periodontitis. There was a higher tendency for implant loss and biological complications in patients previously presenting with severe forms of periodontitis. The strength of the evidence was limited by the heterogeneity of the included studies in terms of study design, population, therapy, unit of analysis, inconsistent definition of baselines and outcomes, as well as by the inadequate reporting of statistical analysis and accounting for confounding factors; thus, meta-analysis could not be performed. CONCLUSIONS: Implants placed in patients treated for periodontal disease are associated with higher incidence of biological complications and lower success and survival rates than those placed in periodontally healthy patients. Severe forms of periodontal disease are associated with higher rates of implant loss. However, it is critical to develop well-designed, long-term prospective studies to provide further substantive evidence on the association of these outcomes. PMID- 26381261 TI - Performance of principal scores to estimate the marginal compliers causal effect of an intervention. AB - We examine the properties of principal scores methods to estimate the causal marginal odds ratio of an intervention for compliers in the context of a randomized controlled trial with non-compliers. The two-stage estimation approach has been proposed for a linear model by Jo and Stuart (Statistics in Medicine 2009; 28:2857-2875) under a principal ignorability (PI) assumption. Using a Monte Carlo simulation study, we compared the performance of several strategies to build and use principal score models and the robustness of the method to violations of underlying assumptions, in particular PI. Results showed that the principal score approach yielded unbiased estimates of the causal marginal log odds ratio under PI but that the method was sensitive to violations of PI, which occurs in particular when confounders are omitted from the analysis. For principal score analysis, probability weighting performed slightly better than full matching or 1:1 matching. Concerning the variables to be included in principal score models, the lowest mean squared error was generally obtained when using the true confounders. Using variables associated with the outcome only but not compliance however yielded very similar performance. PMID- 26381262 TI - A Unique Primer with an Inosine Chain at the 5'-Terminus Improves the Reliability of SNP Analysis Using the PCR-Amplified Product Length Polymorphism Method. AB - Polymerase chain reaction-amplified product length polymorphism (PCR-APLP) is one of the most convenient and reliable methods for single nucleotide polymorphism (SNP) analysis. This method is based on PCR, but uses allele-specific primers containing SNP sites at the 3'-terminus of each primer. To use this method at least two allele-specific primers and one "counter-primer", which serves as a common forward or reverse primer of the allele-specific primers, are required. The allele-specific primers have SNP sites at the 3'-terminus, and another primer should have a few non-complementary flaps at the 5'-terminus to detect SNPs by determining the difference of amplicon length by PCR and subsequent electrophoresis. A major disadvantage of the addition of a non-complementary flap is the non-specific annealing of the primer with non-complementary flaps. However, a design principle for avoiding this undesired annealing has not been fully established, therefore, it is often difficult to design effective APLP primers. Here, we report allele-specific primers with an inosine chain at the 5' terminus for PCR-APLP analysis. This unique design improves the competitiveness of allele-specific primers and the reliability of SNP analysis when using the PCR APLP method. PMID- 26381264 TI - Studies of Cream Seeded Carioca Beans (Phaseolus vulgaris L.) from a Rwandan Efficacy Trial: In Vitro and In Vivo Screening Tools Reflect Human Studies and Predict Beneficial Results from Iron Biofortified Beans. AB - Iron (Fe) deficiency is a highly prevalent micronutrient insufficiency predominantly caused by a lack of bioavailable Fe from the diet. The consumption of beans as a major food crop in some populations suffering from Fe deficiency is relatively high. Therefore, our objective was to determine whether a biofortified variety of cream seeded carioca bean (Phaseolus vulgaris L.) could provide more bioavailable-Fe than a standard variety using in-vivo (broiler chicken, Gallus gallus) and in-vitro (Caco-2 cell) models. Studies were conducted under conditions designed to mimic the actual human feeding protocol. Two carioca beans, a standard (G4825; 58 MUg Fe/g) and a biofortified (SMC; 106 MUg Fe/g), were utilized. Diets were formulated to meet the nutrient requirements of Gallus gallus except for Fe (33.7 and 48.7 MUg Fe/g, standard and biofortified diets, respectively). In-vitro observations indicated that more bioavailable-Fe was present in the biofortified beans and diet (P<0.05). In-vivo, improvements in Fe status were observed in the biofortified bean treatment, as indicated by the increased total-body-Hemoglobin-Fe, and hepatic Fe-concentration (P<0.05). Also, DMT-1 mRNA-expression was increased in the standard bean treatment (P<0.05), indicating an upregulation of absorption to compensate for less bioavailable-Fe. These results demonstrate that the biofortified beans provided more bioavailable Fe; however, the in vitro results revealed that ferritin formation values were relatively low. Such observations are indicative of the presence of high levels of polyphenols and phytate that inhibit Fe absorption. Indeed, we identified higher levels of phytate and quercetin 3-glucoside in the Fe biofortified bean variety. Our results indicate that the biofortified bean line was able to moderately improve Fe-status, and that concurrent increase in the concentration of phytate and polyphenols in beans may limit the benefit of increased Fe concentration. Therefore, specific targeting of such compounds during the breeding process may yield improved dietary Fe-bioavailability. Our findings are in agreement with the human efficacy trial that demonstrated that the biofortified carioca beans improved the Fe-status of Rwandan women. We suggest the utilization of these in vitro and in vivo screening tools to guide studies aimed to develop and evaluate biofortified staple food crops. This approach has the potential to more effectively utilize research funds and provides a means to monitor the nutritional quality of the Fe-biofortified crops once released to farmers. PMID- 26381265 TI - Infection with a Mouse-Adapted Strain of the 2009 Pandemic Virus Causes a Highly Severe Disease Associated with an Impaired T Cell Response. AB - Despite a relatively low fatality rate, the 2009 H1N1 pandemic virus differed from other seasonal viruses in that it caused mortality and severe pneumonia in the young and middle-aged population (18-59 years old). The mechanisms underlying this increased disease severity are still poorly understood. In this study, a human isolate of the 2009 H1N1 pandemic virus was adapted to the mouse (MAp2009). The pathogenicity of the MAp2009 virus and the host immune responses were evaluated in the mouse model and compared to the laboratory H1N1 strain A/Puerto Rico/8/1934 (PR8). The MAp2009 virus reached consistently higher titers in the lungs over 14 days compared to the PR8 virus, and caused severe disease associated with high morbidity and 85% mortality rate, contrasting with the 0% death rate in the PR8 group. During the early phase of infection, both viruses induced similar pathology in the lungs. However, MAp2009-induced lung inflammation was sustained until the end of the study (day 14), while there was no sign of inflammation in the PR8-infected group by day 10. Furthermore, at day 3 post-infection, MAp2009 induced up to 10- to 40-fold more cytokine and chemokine gene expression, respectively. More importantly, the numbers of CD4+ T cells and virus-specific CD8+ T cells were significantly lower in the lungs of MAp2009-infected mice compared to PR8-infected mice. Interestingly, there was no difference in the number of dendritic cells in the lung and in the draining lymph node. Moreover, mice infected with PR8 or MAp2009 had similar numbers of CCR5 and CXCR3-expressing T cells, suggesting that the impaired T cell response was not due to a lack of chemokine responsiveness or priming of T cells. This study demonstrates that a mouse-adapted virus from an isolate of the 2009 pandemic virus interferes with the adaptive immune response leading to a more severe disease. PMID- 26381266 TI - Graphite Carbon-Supported Mo2C Nanocomposites by a Single-Step Solid State Reaction for Electrochemical Oxygen Reduction. AB - Novel graphite-molybdenum carbide nanocomposites (G-Mo2C) are synthesized by a typical solid state reaction with melamine and MoO3 as precursors under inert atmosphere. The characterization results indicate that G-Mo2C composites are composed of high crystallization and purity of Mo2C and few layers of graphite carbon. Mo2C nanoparticles with sizes ranging from 5 to 50 nm are uniformly supported by surrounding graphite layers. It is believed that Mo atom resulting from the reduction of MoO3 is beneficial to the immobilization of graphite carbon. Moreover, the electrocatalytic performances of G-Mo2C for ORR in alkaline medium are investigated by cyclic voltammetry (CV), rotating disk electrode (RDE) and chronoamperometry test with 3M methanol. The results show that G-Mo2C has a considerable catalytic activity and superior methanol tolerance performance for the oxygen reduction reaction (ORR) benefiting from the chemical interaction between the carbide nanoparticles and graphite carbon. PMID- 26381268 TI - Editorial: GABAergic Modulation as Treatment Strategy: Consideration of Several Diseases. PMID- 26381267 TI - Imaging Striatal Microglial Activation in Patients with Parkinson's Disease. AB - This study investigated whether the second-generation translocator protein 18kDa (TSPO) radioligand, [18F]-FEPPA, could be used in neurodegenerative parkinsonian disorders as a biomarker for detecting neuroinflammation in the striatum. Neuroinflammation has been implicated as a potential mechanism for the progression of Parkinson's disease (PD). Positron Emission Tomography (PET) radioligand targeting for TSPO allows for the quantification of neuroinflammation in vivo. Based on genotype of the rs6791 polymorphism in the TSPO gene, 16 mixed affinity binders (MABs) (8 PD and age-matched 8 healthy controls (HCs)), 16 high affinity binders (HABs) (8 PD and age-matched 8 HCs) and 4 low-affinity binders (LABs) (3 PD and 1 HCs) were identified. Total distribution volume (VT) values in the striatum were derived from a two-tissue compartment model with arterial plasma as an input function. There was a significant main effect of genotype on [18F]-FEPPA VT values in the caudate nucleus (p = 0.001) and putamen (p < 0.001), but no main effect of disease or disease x genotype interaction in either ROI. In the HAB group, the percentage difference between PD and HC was 16% in both caudate nucleus and putamen; in the MAB group, it was -8% and 3%, respectively. While this PET study showed no evidence of increased striatal TSPO expression in PD patients, the current findings provide some insights on the possible interactions between rs6791 polymorphism and neuroinflammation in PD. PMID- 26381263 TI - Integrating mRNA and miRNA Weighted Gene Co-Expression Networks with eQTLs in the Nucleus Accumbens of Subjects with Alcohol Dependence. AB - Alcohol consumption is known to lead to gene expression changes in the brain. After performing weighted gene co-expression network analyses (WGCNA) on genome wide mRNA and microRNA (miRNA) expression in Nucleus Accumbens (NAc) of subjects with alcohol dependence (AD; N = 18) and of matched controls (N = 18), six mRNA and three miRNA modules significantly correlated with AD were identified (Bonferoni-adj. p<= 0.05). Cell-type-specific transcriptome analyses revealed two of the mRNA modules to be enriched for neuronal specific marker genes and downregulated in AD, whereas the remaining four mRNA modules were enriched for astrocyte and microglial specific marker genes and upregulated in AD. Gene set enrichment analysis demonstrated that neuronal specific modules were enriched for genes involved in oxidative phosphorylation, mitochondrial dysfunction and MAPK signaling. Glial-specific modules were predominantly enriched for genes involved in processes related to immune functions, i.e. cytokine signaling (all adj. p<= 0.05). In mRNA and miRNA modules, 461 and 25 candidate hub genes were identified, respectively. In contrast to the expected biological functions of miRNAs, correlation analyses between mRNA and miRNA hub genes revealed a higher number of positive than negative correlations (chi2 test p<= 0.0001). Integration of hub gene expression with genome-wide genotypic data resulted in 591 mRNA cis-eQTLs and 62 miRNA cis-eQTLs. mRNA cis-eQTLs were significantly enriched for AD diagnosis and AD symptom counts (adj. p = 0.014 and p = 0.024, respectively) in AD GWAS signals in a large, independent genetic sample from the Collaborative Study on Genetics of Alcohol (COGA). In conclusion, our study identified putative gene network hubs coordinating mRNA and miRNA co-expression changes in the NAc of AD subjects, and our genetic (cis-eQTL) analysis provides novel insights into the etiological mechanisms of AD. PMID- 26381269 TI - Acridine Orange is an Effective Anti-Cancer Drug that Affects Mitochondrial Function in Osteosarcoma Cells. AB - Acridine orange (AO) is an antimalarial drug that accumulates into acidic cellular compartments. Lysosomes are quite acidic in cancer cells, and on this basis we have demonstrated that photoactivated AO is selectively toxic in sarcomas. However, photodynamic therapy is only locally effective, and cannot be used to eradicate systemic residual disease. In this study, we have evaluated the activity of non-photoactivated AO on sensitive and chemoresistant osteosarcoma (OS) cells to be considered for the systemic delivery. Since lysosomes are even more acidic in chemoresistant cells (MDR), we found that AO accumulation was significantly higher in the lysosomes of MDR in respect to parental cells, and in both cell types, therapeutic doses of AO significantly inhibited cell growth. However, the level of growth inhibition was inversely related to the level of lysosomal uptake of AO, suggesting that the main target of this agent is indeed extralysosomal. A significant reduction of intracellular ATP content and of the expression of mitochondrial complex III suggests a mitochondrial targeting. Notably, MDR cells showed a lower mitochondrial activity. Finally, the combined treatment of AO with the anticancer agent doxorubicin (DXR) significantly increased chemotoxicity by promoting DXR mitochondrial targeting, as revealed by the further reduction in ATP intracellular content. In conclusion, AO is able to effectively target both sensitive and resistant OS cells through mitotoxicity. PMID- 26381270 TI - Altered intestinal neuroendocrine gene expression in humans with obesity. AB - OBJECTIVE: Gastrointestinal hormones are critically involved in the regulation of food intake and body weight. Previous studies support an interplay between gastrointestinal hormones and the serotonergic system. This study explored intestinal neuroendocrine expression patterns in humans with obesity versus nonobese humans. METHODS: Jejunum samples were collected from 164 humans with obesity (120 women; BMI (mean +/- SD): 43.5 +/- 6.6 kg/m(2) ) while they underwent Roux-en-Y gastric bypass surgery and from 18 nonobese humans (7 women; BMI: 23.5 +/- 3.0 kg/m(2) ) undergoing distinct intestinal surgeries. mRNA expression of cholecystokinin (CCK), peptide YY3-36 (PYY), nesfatin1, ghrelin, ghrelin O-acyltransferase (GOAT), leptin, leptin receptor (leptinR), glucagon like-peptide 1 receptor (GLP1R), serotonin transporter (SERT), tryptophan hydroxylase 1 (TPH1), and serotonin receptor 3A (5HT3A R) was determined with qRT PCR. Ghrelin and GOAT protein expression was quantified using immunohistological stainings. Statistical analyses were performed with SPSS. RESULTS: Jejunum samples from humans with obesity showed a higher expression of GOAT (mRNA and protein), TPH1, and SERT mRNA compared with the nonobese humans (all P < 0.05). Positive correlations were observed between TPH1, CCK, PYY, and nesfatin1 in nonobese and GOAT, ghrelin, TPH1, SERT, CCK, and PYY in humans with obesity (all P < 0.01). CONCLUSIONS: Our top-down approach substantiates the dysregulation of jejunal neuroendocrine hormones in obesity. PMID- 26381271 TI - A Framework to Simplify Combined Sampling Strategies in Rosetta. AB - A core task in computational structural biology is the search of conformational space for low energy configurations of a biological macromolecule. Because conformational space has a very high dimensionality, the most successful search methods integrate some form of prior knowledge into a general sampling algorithm to reduce the effective dimensionality. However, integrating multiple types of constraints can be challenging. To streamline the incorporation of diverse constraints, we developed the Broker: an extension of the Rosetta macromolecular modeling suite that can express a wide range of protocols using constraints by combining small, independent modules, each of which implements a different set of constraints. We demonstrate expressiveness of the Broker through several code vignettes. The framework enables rapid protocol development in both biomolecular design and structural modeling tasks and thus is an important step towards exposing the rich functionality of Rosetta's core libraries to a growing community of users addressing a diverse set of tasks in computational biology. PMID- 26381272 TI - Comparative efficacy of anti-diabetic agents on nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized and non-randomized studies. AB - BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has a high prevalence in patients with type 2 diabetes mellitus (T2DM). In this study, we sought to provide a comprehensive assessment regarding the effects of anti-diabetic agents on NAFLD in patients with T2DM. METHODS: MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched for randomized controlled trials (RCTs) with different anti-diabetic agents in T2DM. Observational trials were also recruited to expand our population. Hepatic fat content and liver histology were evaluated as primary outcomes. Pooled estimates were calculated using a fixed effect model. RESULTS: One thousand one hundred ninety-six participants in 19 RCTs and 14 non-randomized studies were included. Evidence from RCTs and observational studies suggested that greater hepatic fat content reduction and improved liver histology were seen in thiazolidinediones for 12-72 weeks; glucagon-like peptide-1 receptor agonists had beneficial effects on hepatic fat content after 26-50 weeks intervention, and insulin/metformin combination with 3 7 months improved hepatic fat content. Initiating metformin or dapagliflozin showed no benefit on hepatic fat content or liver histology in 16-48 weeks. Besides, nateglinide for 18 months was reported in a small sample-size RCT to improve hepatic fat content and liver histology. Sitagliptin therapy of 1 year also provided benefit on nonalcoholic steatohepatitis score in an observational study. CONCLUSIONS: For T2DM with NAFLD, administrating thiazolidinediones and glucagon-like peptide-1 receptor agonists seems to provide more identified advances in attenuating hepatic fat content. Further RCTs are warranted to assess the efficacy of various hypoglycemic agents on clinical outcomes associated with NAFLD in T2DM. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26381273 TI - Feeding of Whitefly on Tobacco Decreases Aphid Performance via Increased Salicylate Signaling. AB - BACKGROUND: The feeding of Bemisia tabaci nymphs trigger the SA pathway in some plant species. A previous study showed that B. tabaci nymphs induced defense against aphids (Myzus persicae) in tobacco. However, the mechanism underlying this defense response is not well understood. METHODOLOGY/PRINCIPAL FINDINGS: Here, the effect of activating the SA signaling pathway in tobacco plants through B. tabaci nymph infestation on subsequent M. persicae colonization is investigated. Performance assays showed that B. tabaci nymphs pre-infestation significantly reduced M. persicae survival and fecundity systemically in wild type (WT) but not salicylate-deficient (NahG) plants compared with respective control. However, pre-infestation had no obvious local effects on subsequent M. persicae in either WT or NahG tobacco. SA quantification results indicated that the highest accumulation of SA was induced by B. tabaci nymphs in WT plants after 15 days of infestation. These levels were 8.45- and 6.14-fold higher in the local and systemic leaves, respectively, than in controls. Meanwhile, no significant changes of SA levels were detected in NahG plants. Further, biochemical analysis of defense enzymes polyphenol oxidase (PPO), peroxidase (POD), beta-1,3 glucanase, and chitinase demonstrated that B. tabaci nymph infestation increased these enzymes' activity locally and systemically in WT plants, and there was more chitinase and beta-1, 3-glucanase activity systemically than locally, which was opposite to the changing trends of PPO. However, B. tabaci nymph infestation caused no obvious increase in enzyme activity in any NahG plants except POD. CONCLUSIONS/SIGNIFICANCE: In conclusion, these results underscore the important role that induction of the SA signaling pathway by B. tabaci nymphs plays in defeating aphids. It also indicates that the activity of beta-1, 3-glucanase and chitinase may be positively correlated with resistance to aphids. PMID- 26381274 TI - TRPV4 Channels in Human White Adipocytes: Electrophysiological Characterization and Regulation by Insulin. AB - Intracellular calcium homeostasis in adipocytes is important for the regulation of several functions and is involved in pathological changes in obesity and other associated diseases. Transient Receptor Potential Vanilloid 4 (TRPV4) channels are an important route for calcium entry that operates in a variety of cells and intervenes in a number of functions. In this study, the expression and operation of TRPV4 channels in human cultured adipocytes was evaluated using RT-PCR, Western blotting, the whole-cell patch-clamp technique and fluorescence measurements to characterize these channels and determine intracellular calcium responses. Both the hypoosmolarity and 4alpha-phorbol-didecanoate (4alphaPDD), a specific TRPV4 agonist, induced a similar HC-067047-sensitive current, which was predominantly inward, and an intracellular Ca(2+) concentration increase, which was exclusively dependent on extracellular calcium, and membrane depolarization. The current had a reverse potential of +31 +/- 6 mV and exhibited preferential permeability to Ca(2+) . Insulin, which regulates metabolic homeostasis in adipocytes, attenuated the TRPV4-mediated effects. These results confirm the function of TRPV4 in human cultured adipocytes and its regulation by insulin. J. Cell. Physiol. 231: 954-963, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26381275 TI - The effects of ketoconazole and rifampin on the single-dose pharmacokinetics of crizotinib in healthy subjects. AB - PURPOSE: To investigate the potential effects of strong CYP3A inhibitor ketoconazole and strong CYP3A inducer rifampin on the pharmacokinetics of crizotinib in human. METHODS: Two separate open-label, 2-period, 2-treatment, 1 sequence, crossover, single-dose studies were conducted in healthy subjects with and without ketoconazole or rifampin. Series of plasma samples were collected after each crizotinib dose to determine concentration of crizotinib and its metabolite PF-06260182. Relevant pharmacokinetic (PK) parameters for crizotinib and PF096269182 were estimated by standard non-compartmental analysis (NCA) method. RESULTS: Co-administration of a single 150-mg oral dose of crizotinib with the strong CYP3A inhibitor ketoconazole resulted in an area under the plasma concentration curve extrapolated to infinity (AUC0-inf) 3.2-fold that for crizotinib alone. Co-administration of a single 250-mg crizotinib dose with the strong CYP3A inducer rifampin caused an 82 % decrease in crizotinib AUC0-inf. Respective increases and decreases in systemic exposure to the crizotinib metabolite PF-06260182 following co-administration of ketoconazole and rifampin were greater than those seen for crizotinib. CONCLUSIONS: These findings suggest that CYP3A plays an important role in the metabolism of both crizotinib and PF 06260182, with the extent of this role being greater for PF-06260182. There were no serious adverse events or deaths and no dose reductions or temporary or permanent discontinuations due to drug-related adverse events in either study. PMID- 26381276 TI - Evaluation of the immunochromatographic (Leptocheck) test for detection of specific antibodies against leptospires. AB - BACKGROUND: Leptospirosis is a febrile worldwide zoonosis. Routine diagnosis of leptospiral infection is based on demonstration of specific antibodies with serological tests. Performance of the reference serological test, the microscopic agglutination test (MAT), requires significant expertise. The aim of our study was to find out if leptospiral infection can be proven with simple, rapid, commercially available immunochromatographic Leptocheck test in order to introduce it for the first level diagnosis in emergency cases with less specialized laboratory staff. METHODS: In all, 590 serum samples of patients with clinical manifestations suggestive of leptospirosis were collected and tested with MAT and Leptocheck test. For confirmation of the results some other diagnostic methods such as polymerase chain reaction (PCR) and Leptospira isolation were performed. RESULTS: Results of both serological tests were consistent in 576/590 (97.63%) cases but Leptocheck gave more positive results in comparison to MAT (36 and 12, respectively) at first patient's testing. Following up the patient, MAT became positive in majority of Leptocheck positive patients at first visit. Leptospiral DNA was detected in nine blood and six urine samples belonging to thirteen different patients while only two samples were culture positive. CONCLUSION: In comparison with serological tests, PCR and culture have low sensitivity. According to our findings we conclude that Leptocheck test can prove leptospiral infection and could be used for rapid diagnosis of leptospirosis, later the sample should be confirmed with MAT. PMID- 26381277 TI - Biosimilarity Versus Manufacturing Change: Two Distinct Concepts. AB - As products of living cells, biologics are far more complicated than small molecular-weight drugs not only with respect to size and structural complexity but also their sensitivity to manufacturing processes and post-translational changes. Most of the information on the manufacturing process of biotherapeutics is proprietary and hence not fully accessible to the public. This information gap represents a key challenge for biosimilar developers and plays a key role in explaining the differences in regulatory pathways required to demonstrate biosimilarity versus those required to ensure that a change in manufacturing process did not have implications on safety and efficacy. Manufacturing process changes are frequently needed for a variety of reasons including response to regulatory requirements, up scaling production, change in facility, change in raw materials, improving control of quality (consistency) or optimising production efficiency. The scope of the change is usually a key indicator of the scale of analysis required to evaluate the quality. In most cases, where the scope of the process change is limited, only quality and analytical studies should be sufficient while comparative clinical studies can be required in case of major changes (e.g., cell line changes). Biosimilarity exercises have been addressed differently by regulators on the understanding that biosimilar developers start with fundamental differences being a new cell line and also a knowledge gap of the innovator's processes, including culture media, purification processes, and potentially different formulations, and are thus required to ensure that differences from innovators do not result in differences in efficacy and safety. PMID- 26381280 TI - Interaction of Nd dopants with broadband emission centers in Bi2O3-B2O3 glass: local energy balance and its influence on optical properties. AB - Chemical and energetic interactions between broadband infrared intrinsic emission centers (IECs) of bismuthates and extrinsic emission centers (EECs) of Nd2O3 dopants were optically and electronically investigated. Although no visible absorption from the IEC was found in untreated Bi2O3-B2O3 glass, it was clearly observed after a moderate thermal treatment of <200 degrees C, indicating chemical activity of O-deficient sites as the origin of IECs. On the other hand, Nd2O3 doping chemically stabilized the Bi2O3-B2O3 glass and suppressed IEC formation. By using a microwave measurement sensitive to electric dipoles, we found a 'switching' in local energy balance resulting from the Nd2O3 doping. This was explained by metallization of the O-deficient sites in the Bi2O3-B2O3 glass and multi-phonon excitation of IEC and EEC complexes in the Nd2O3-Bi2O3-B2O3 glass phosphor. Although the electric dipole observed by the microwave measurement was not necessarily caused by IEC, emission properties of the IEC and EEC complexes were consistent with energy balance switching; emissions from IECs after thermal treatment were quenched by EECs with multi-phonon excitation. PMID- 26381279 TI - Pharmacokinetic Properties of a Novel D-Peptide Developed to be Therapeutically Active Against Toxic beta-Amyloid Oligomers. AB - PURPOSE: It has been shown that amyloid beta (Abeta) oligomers play an important role in the pathology of Alzheimer's disease (AD). D3, a peptide consisting solely of D-enantiomeric amino acid residues, was developed to specifically eliminate Abeta oligomers and is therapeutically active in transgenic AD mice. D peptides have several advantages over L-peptides, but little is known about their pharmacokinetic potential in vivo. Here, we analysed the pharmacokinetic properties of RD2, a rationally designed and potent D3 derivative. METHODS: The pharmacokinetic analysis was performed using (3)H-RD2 after administration via several routes in mice. The time dependent amount of radiolabelled RD2 was measured in plasma and several organ homogenates by liquid scintillation counting. Furthermore, binding to plasma proteins was estimated. RESULTS: RD2 penetrates into the brain, where it is thought to implement its therapeutic function. All administration routes result in a maximal brain concentration per dose (Cmax/D) of 0.06 (MUg/g)/(mg/kg) with brain/plasma ratios ranging between 0.7 and 1.0. RD2 shows a small elimination constant and a long terminal half-life in plasma of more than 2 days. It also exhibits high bioavailability after i.p., s.c. or p.o. administration. CONCLUSIONS: These excellent pharmacokinetic properties confirm that RD2 is a very promising drug candidate for AD. PMID- 26381278 TI - Polymeric Micelles: Recent Advancements in the Delivery of Anticancer Drugs. AB - Nanotechnology, in health and medicine, extensively improves the safety and efficacy of different therapeutic agents, particularly the aspects related to drug delivery and targeting. Among various nano-carriers, polymer based macromolecular approaches have resulted in improved drug delivery for the diseases like cancers, diabetes, autoimmune disorders and many more. Polymeric micelles consisting of hydrophilic exterior and hydrophobic core have established a record of anticancer drug delivery from the laboratory to commercial reality. The nanometric size, tailor made functionality, multiple choices of polymeric micelle synthesis and stability are the unique properties, which have attracted scientists and researchers around the world to work upon in this opportunistic drug carrier. The capability of polymeric micelles as nano-carriers are nowhere less significant than nanoparticles, liposomes and other nanocarriers, as per as the commercial feasibility and presence is concerned. In fact polymeric micelles are among the most extensively studied delivery platforms for the effective treatment of different cancers as well as non-cancerous disorders. The present review highlights the sequential and recent developments in the design, synthesis, characterization and evaluation of polymeric micelles to achieve the effective anticancer drug delivery. The future possibilities and clinical outcome have also been discussed, briefly. PMID- 26381281 TI - Interrater Reliability of Pupillary Assessments. AB - BACKGROUND: Subjective scoring of pupil reactivity is a fundamental element of the neurological examination for which the pupillometer provides an objective measure. METHODS: This single-blinded observational study examined interrater reliability of pupil exam findings between two practitioners and between practitioners and a pupillometer. RESULTS: From 2329 paired assessments, the interrater reliability between practitioners was only moderate for pupil size (k = 0.54), shape (k = 0.62), and reactivity (k = 0.40). Only 33.3% of pupils scored as non-reactive by practitioners were scored as non-reactive by pupillometry. CONCLUSIONS: Despite the strong emphasis placed on the traditional pupil examination, especially for patients with a neurological illness, there is limited interrater reliability for subjective scoring of pupillary assessments. Thus, the use of automated pupillometers should be examined as a potential method to increase the reliability of measuring of pupil reactivity. PMID- 26381282 TI - Impact of Perihemorrhagic Edema on Short-Term Outcome After Intracerebral Hemorrhage. AB - BACKGROUND: Intracerebral hemorrhage (ICH) is a devastating disease with ICH volume being the main predictor of poor outcome. The prognostic role of perihemorrhagic edema (PHE) is still unclear; however, available data are mainly derived from analyses during the first days after symptom onset. As PHE growth may continue up to 14 days after ICH, we evaluated PHE over a longer period of time and investigated its impact on short-term clinical outcome. METHODS: In this monocentric retrospective cohort study, patients with spontaneous supratentorial ICH were identified from our institutional data base. Different time points of CT scans were merged to time clusters for better comparison (day 1, 2-3, 4-6, 7-9, 10-12). Absolute volumes of ICH and PHE were obtained using a validated semiautomatic volumetric algorithm. Clinical outcome at discharge was assessed using the modified Rankin Scale (0-3 = favorable, 4-6 = poor). RESULTS: 220 patients (83 with favorable, 137 with poor outcome) were included in the final analysis. Mean ICH volume on admission was 22.8 [standard deviation (SD) 24.6] cm(3). Mean absolute PHE volume on admission was 22.5 (SD 20.8) cm(3) and increased to a mean peak volume of 38.1 (SD 31.4) cm(3) during 6.7 (SD 4.1) days on average. Besides GCS on admission, functional status before ICH, peak hematoma volume, lobar localization and fever burden, and high peak PHE volume predicted poor outcome at discharge [OR 0.977 (95 % CI 0.957-0.998)] in the multivariable analysis. CONCLUSIONS: PHE may have a negative impact on short-term functional outcome after ICH and therefore represent a possible treatment target. PMID- 26381284 TI - Susan Greenfield replies to Vaughan Bell and colleagues. PMID- 26381283 TI - EGFR and KRAS Mutations in ALK-Positive Lung Adenocarcinomas: Biological and Clinical Effect. AB - INTRODUCTION: In lung adenocarcinoma (ADC), anaplastic lymphoma receptor tyrosine kinase (ALK) rearrangements are mutually exclusive with epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations. However, the existence of double-positive (DP) patients have been sporadically described. We identified DP cases in therapy-naive ALK-rearranged ADC and characterized the biology of these tumors to better understand the clinical response to tyrosine kinase inhibitors (TKIs). MATERIALS AND METHODS: We selected 42 ALK-positive ADCs from a multicentric series of 301 cases of ADCs. A mutational analysis was performed using Sanger and/or pyrosequencing to address exons 18-21 of EGFR and codons 12-13 of the KRAS gene. In addition, the KRAS and EGFR copy number was investigated using fluorescent in situ hybridization. DP patients were treated with TKIs, and their response was evaluated according to the Response Evaluation Criteria in Solid Tumors criteria. RESULTS: Eight of 42 ALK-positive ADCs (19%) demonstrated a concomitant mutation in the EGFR (3 cases) or KRAS (5 cases) genes and were classified as DP. All DP cases displayed copy number gains in the EGFR or KRAS gene because of polysomy or gene amplification. In the latter cases, a mutant allele-specific imbalance was observed. Four patients were treated with TKIs. The 2 EGFR-mutant DP patients demonstrated a better response to crizotinib compared with erlotinib. The 2 KRAS-mutant DP patients experienced opposite responses to crizotinib. CONCLUSION: The incidence of DP ADC is not negligible. Patients with ALK/EGFR might benefit more from crizotinib compared with erlotinib administration, although the efficacy of TKIs in patients with ALK/KRAS remains unclear. An integrated targeted therapy should be considered for patients with DP ADC. PMID- 26381285 TI - Exposure to Fentanyl After Transdermal Patch Administration for Cancer Pain Management. AB - This study aimed to describe exposure after fentanyl transdermal patch administration in patients with advanced cancer to quantify variability around the exposure. Patients (n = 56) with advanced cancer who received transdermal fentanyl (Durogesic(r); median dose, 50 MUg/h; range, 12-200 MUg/h) provided venous blood samples (n = 163) at various times (0.5-72 hours) during several patch application intervals. Plasma fentanyl concentration was determined (median, 0.9 MUg/L; range, 0.04-9.7 MUg/L) by high-performance liquid chromatography coupled to tandem mass spectrometry. Pharmacokinetic analysis was performed using nonlinear mixed-effects modeling with NONMEM. A 1-compartment distribution model with first-order absorption and elimination described fentanyl exposure after transdermal patch administration. Fentanyl apparent clearance (between-subject variability [BSV], %) was estimated at 122 L/h/70 kg and 38.5%, respectively. The absorption rate constant was 0.013 h(-1) . Between-occasion variability on apparent clearance was 22.0%, which was lower than BSV, suggesting predictable exposure within the same patient and justifying therapeutic drug monitoring. Except for weight-based dosing, no other patient characteristic could be identified to guide initial fentanyl dose selection in patients with advanced cancer. PMID- 26381286 TI - Investigation of Synaptic Tagging/Capture and Cross-capture using Acute Hippocampal Slices from Rodents. AB - Synaptic tagging and capture (STC) and cross-tagging are two important mechanisms at cellular level that explain how synapse-specificity and associativity is achieved in neurons within a specific time frame. These long-term plasticity related processes are the leading candidate models to study the basis of memory formation and persistence at the cellular level. Both STC and cross-tagging involve two serial processes: (1) setting of the synaptic tag as triggered by a specific pattern of stimulation, and (2) synaptic capture, whereby the synaptic tag interacts with newly synthesized plasticity-related proteins (PRPs). Much of the understanding about the concepts of STC and cross-tagging arises from the studies done in CA1 region of the hippocampus and because of the technical complexity many of the laboratories are still unable to study these processes. Experimental conditions for the preparation of hippocampal slices and the recording of stable late-LTP/LTD are extremely important to study synaptic tagging/cross-tagging. This video article describes the experimental procedures to study long-term plasticity processes such as STC and cross-tagging in the CA1 pyramidal neurons using stable, long-term field-potential recordings from acute hippocampal slices of rats. PMID- 26381287 TI - The systemic kainic acid rat model of temporal lobe epilepsy: Long-term EEG monitoring. AB - Animal models reproducing the characteristics of human epilepsy are essential for the elucidation of the pathophysiological mechanisms. In epilepsy research there is ongoing debate on whether the epileptogenic process is a continuous process rather than a step function. The aim of this study was to assess progression of epileptogenesis over the long term and to evaluate possible correlations between SE duration and severity with the disease progression in the kainic acid model. Rats received repeated KA injections (5mg/kg) until a self-sustained SE was elicited. Continuous depth EEG recording started before KA injection and continued for 30 weeks. Mean seizure rate progression could be expressed as a sigmoid function and increased from 1 +/- 0.2 seizures per day during the second week after SE to 24.4 +/- 6.4 seizures per day during week 30. Seizure rate progressed to a plateau phase 122 +/- 9 days after SE. However, the individual seizure rate during this plateau phase varied between 14.5 seizures and 48.6 seizures per day. A circadian rhythm in seizure occurrence was observed in all rats. Histological characterization of damage to the dentate gyrus in the KA treated rats confirmed the presence of astrogliosis and aberrant mossy fiber sprouting in the dentate gyrus. This long-term EEG monitoring study confirms that epileptogenesis is a continuous process rather than a step function. PMID- 26381288 TI - The role of steroid hormones in breast cancer stem cells. AB - Breast cancer stem cells (BCSCs) are potent tumor-initiating cells in breast cancer, the most common cancer among women. BCSCs have been suggested to play a key role in tumor initiation which can lead to disease progression and formation of metastases. Moreover, BCSCs are thought to be the unit of selection for therapy-resistant clones since they survive conventional treatments, such as chemotherapy, irradiation, and hormonal therapy. The importance of the role of hormones for both normal mammary gland and breast cancer development is well established, but it was not until recently that the effects of hormones on BCSCs have been investigated. This review will discuss recent studies highlighting how ovarian steroid hormones estrogen and progesterone, as well as therapies against them, can regulate BCSC activity. PMID- 26381289 TI - The current landscape of television and movies in medical education. AB - BACKGROUND: Using commercially available television and movies is a potentially effective tool to foster humanistic, compassionate and person-centred orientations in medical students. AIM: We reviewed pedagogical applications of television and movies in medical education to explore whether and why this innovation holds promise. METHODS: We performed a literature review to provide a narrative summary on this topic. RESULTS: Further studies are needed with richer descriptions of innovations and more rigorous research designs. CONCLUSION: As we move toward evidence-informed education, we need an evidence- based examination of this topic that will move it beyond a 'show and tell' discussion toward meaningful implementation and evaluation. Further exploration regarding the theoretical basis for using television and movies in medical education will help substantiate continued efforts to use these media as teaching tools. PMID- 26381290 TI - Laryngeal penetration on videofluoroscopic swallowing study is associated with increased pneumonia in children. AB - OBJECTIVES: To determine whether children with laryngeal penetration on videofluoroscopic swallowing study are at higher risk for pneumonia than those with normal findings. METHODS: We reviewed the charts of 235 pediatric patients presenting to our Swallowing and Dysphagia clinic for videofluoroscopic swallowing study over a 3-year period. Patients with unsuccessful swallowing studies, incomplete charts, extra-laryngeal etiologies for recurrent pneumonia, or who were lost to follow up were excluded. Out of the 165 patients remaining, 58 had normal findings, 59 had laryngeal penetration, and 48 had tracheobronchial aspiration. The number of cases of pneumonia, aspiration events, and demographic data were recorded for all patients. RESULTS: Children with laryngeal penetration on videofluoroscopic swallowing study had significantly (P=0.032) more pneumonia than patients with neither penetration nor aspiration (median 2 vs. 0; mean 2.22 vs. 1.60). Furthermore, analysis revealed that glottic abnormalities (e.g. laryngeal cleft) represented a significant independent risk factor (P=0.004) for pneumonia and aspiration, while being diagnosed with a syndrome did not (P=0.343). CONCLUSION: To our knowledge, this is the first study to demonstrate that laryngeal penetration on videofluoroscopic swallowing study is associated with significantly more cases of pneumonia in children. While this remains a retrospective study demonstrating a weak association, the results suggest a need for future prospective studies to evaluate this important clinical question in children. PMID- 26381291 TI - DUSP16 ablation arrests the cell cycle and induces cellular senescence. AB - Dual-specificity phosphatases (DUSPs) are a family of protein phosphatases that dephosphorylate both phosphotyrosine and phosphoserine/phosphothreonine residues. DUSPs are de-regulated in many human diseases, including cancers. However, the function of DUSPs in tumorigenesis remains largely unknown. Here, using short hairpin RNA-based gene knockdown, we found that several members of the DUSP family play critical roles in regulating cell proliferation. In particular, we showed that DUSP16 ablation leads to a G1/S transition arrest, reduced incorporation of 5-bromodeoxyuridine, enhanced senescence-associated beta galactosidase activity, and formation of senescence-associated heterochromatic foci. Mechanistically, DUSP16 silencing causes cellular senescence by activating the tumor suppressors p53 and Rb. The phosphatase activity of DUSP16 is necessary for antagonizing cellular senescence. Importantly, the expression levels of DUSP16 are up-regulated in human liver cancers, and are positively correlated with tumor cell proliferation. Taken together, our findings indicate that DUSP16 plays a role in tumorigenesis by protecting cancer cells from senescence. PMID- 26381295 TI - Detection of human polyomaviruses MCPyV, HPyV6, and HPyV7 in malignant and non malignant tonsillar tissues. AB - Merkel cell polyomavirus (MCPyV) is associated with Merkel cell carcinoma (MCC), a rare skin malignancy. Human polyomavirus six and seven (HPyV6 and HPyV7) were identified on a skin but have not been associated with any pathology. The serology data suggest that infection with polyomaviruses occurs in childhood and they are widespread in population. However, the site of persistent infection has not been identified. Altogether, 103 formalin-fixed paraffin-embedded (FFPE) specimens and five fresh frozen tissues (FF) of non-malignant tonsils and 97 FFPE and 15 FF samples of tonsillar carcinomas were analyzed by qPCR for the presence of MCPyV, HPyV6, and HPyV7 DNA. All MCPyV DNA positive FF tissues were screened for the expression of early viral transcripts. Overall prevalence of MCPyV, HPyV6, and HPyV7 in non-malignant tonsillar tissues was 10.2%, 4.6%, and, 0.9%, respectively. The prevalence of MCPyV DNA in non-malignant tonsils increased with age (P < 0.05). While the prevalence of MCPyV DNA was significantly higher in the tumors than non-malignant tissues (35.7% vs. 10.2%) (P < 0.001), the prevalence of HPyV6 DNA (5.4% vs. 4.6%) and HPyV7 DNA (1.8% vs. 0.9%) were comparable. In all MCPyV DNA positive FF tissues early transcripts were detected. MCPyV, HPyV6, and HPyV7 DNAs were found in tonsils, suggesting that the tonsils may be a site of viral latency. The viral load was low indicating that only a fraction of cells are infected. The higher prevalence of MCPyV DNA was detected in tonsillar tumors but there was no difference in the viral load between tumor and healthy tissues. PMID- 26381296 TI - Masking with faces in central visual field under a variety of temporal schedules. AB - With a few exceptions, previous studies have explored masking using either a backward mask or a common onset trailing mask, but not both. In a series of experiments, we demonstrate the use of faces in central visual field as a viable method to study the relationship between these two types of mask schedule. We tested observers in a two alternative forced choice face identification task, where both target and mask comprised synthetic faces, and show that a simple model can successfully predict masking across a variety of masking schedules ranging from a backward mask to a common onset trailing mask and a number of intermediate variations. Our data are well accounted for by a window of sensitivity to mask interference that is centered at around 100 ms. PMID- 26381297 TI - The Existence of Tricyanomethane. AB - Calcium tricyanomethanide reacts with hydrogen fluoride under formation of tricyanomethane and Ca(HF2)2. Tricyanomethane is stable below -40 degrees C and was characterized by IR, Raman, and NMR spectroscopy. The vibrational spectra were compared to the quantum-chemical frequencies at the PBE1PBE/6-311G(3df,3dp) level of theory and confirm the predicted C(3v) symmetry of the molecule with regular C-H (109.8 pm), C-C (146.7 pm), and C=N (114.7 pm) bonds. PMID- 26381298 TI - Image-enhanced endoscopy: clinical frontier and future perspectives. PMID- 26381299 TI - Image-enhanced capsule endoscopy for characterization of small bowel lesions. AB - Video capsule endoscopy has revolutionized direct endoscopic imaging of the gut. Small-bowel video capsule endoscopy (SBVCE) is now the first-line procedure for exploring the small bowel in case of obscure digestive bleeding and has also some room in case of Crohn's disease, coeliac disease and polyposis syndrome. In case of obscure digestive bleeding the main lesions are angioectasias, erosions/ulcerations and tumors. As for conventional optical endoscopy search was done for improving the detection and characterization of small-bowel lesions. The Fujinon Intelligent Chromoendoscopy (FICE) has been adapted on the software of the SBVCE (Given Imaging((r))/Medtronics). Although there are some conflicting results on the efficacy of FICE for detecting more lesions than with conventional light, it is now recognized that FICE - particularly the setting 1 - may enhance the delineation or characterization of lesions. The use of three-dimensional representation technique is now feasible but still needs further research. PMID- 26381300 TI - Detection and characterization of early malignancy in the esophagus: what is the best management algorithm? AB - Barrett's esophagus is a known precursor for esophageal adenocarcinoma. Early detection of dysplasia provides a window of opportunity for curative intervention. Several image-enhanced technologies have been developed to improve visualization of neoplasia. These however have not been found to be superior to the standard four quadrant random biopsy protocol. Patients are risk-stratified based on the degree of dysplasia found on biopsies and undergo either surveillance or treatment. Endoscopic therapy has become the mainstay of treatment for early neoplasia. PMID- 26381301 TI - Red flag imaging in Barrett's esophagus: does it help to find the needle in the haystack? AB - Esophageal Adenocarcinoma (EAC) has suffered a sharp increase on its incidence for the last decades, and it is associated with a poor prognosis. Barrett's Esophagus (BE) is the most important identifiable risk factor for the progression to esophageal adenocarcinoma. The key to prevent and provide a curative treatment of esophageal adenocarcinoma is the detection and eradication of early neoplasia in patients with esophagus. Endoscopic surveillance is evolving from a blind or random four quadrant biopsies protocol (Seattle protocol) to a more targeted approach. A detailed white light examination with high-resolution endoscopy is the cornerstone for recognition of early neoplastic lesions in BE. Additional imaging modalities may enhance targeting of lesions or provide more information at a focused level. There are emerging data that some of these new modalities can increase the yield of detecting dysplasia, although its routine use has yet to be validated. PMID- 26381302 TI - Molecular biomarkers added to image-enhanced endoscopic imaging: will they further improve diagnostic accuracy? AB - Barrett's esophagus (BE) is a premalignant condition for esophageal adenocarcinoma (EAC) which has dismal prognosis. The risk of progression from BE to EAC increases with dysplasia grade. The purpose of surveillance exams in BE is to detect dysplasia at an early stage and intervene before development of EAC. However, the current surveillance practices have not been effective in reducing EAC incidence. Major limitations of this strategy include challenges in identifying dysplasia during endoscopic surveillance, which leads to sampling error and subjectivity in the histological diagnosis of dysplasia due to interobserver variation amongst pathologists. Advanced imaging techniques may allow targeted biopsy of suspicious foci with incremental yield in dysplasia detection and reduce sampling error. Molecular biomarker panels have the potential to objectively assess progression risk without the subjectivity associated with histology. Combining molecular markers with advanced imaging appears to be a promising strategy to further improve risk stratification and reduce EAC incidence and mortality. Few studies have investigated this strategy so far and the results are promising. Further research on different permutations between the available biomarkers and imaging techniques will help us determine the best possible combination that detects dysplasia with high sensitivity and specificity. Further research is needed to establish the combined strategy's cost effectiveness and feasibility. PMID- 26381303 TI - Advanced endoscopic imaging for early gastric cancer. AB - Considerable numbers of early gastric cancers can be missed or misdiagnosed with conventional white light imaging endoscopy (WLI), thus advanced endoscopic imaging modalities have been applied to overcome the issue. High definition endoscopy can improve diagnostic accuracy, but still misses 20-25% of early gastric cancer. Magnifying endoscopy combined with narrow band imaging (NBI) allows for very high accuracy, with sensitivity and specificity of over 95%. The algorithm for magnifying endoscopy diagnosis of gastric cancer is composed of 1) presence of demarcation line, and 2) presence of irregular microsurface and/or microvascular pattern. Ultra-high magnification of 400 times with endocytoscopy (ECS) can produce images reflecting structural and cellular atypia. Using high grade ECS atypia as the diagnostic criteria for gastric cancer, ECS achieves a high diagnostic accuracy (86% of sensitivity, 100% of specificity) although approximately 10% of target lesions are not assessable because of poor dye staining. PMID- 26381304 TI - Characterization of lesions in the stomach: will confocal laser endomicroscopy replace the pathologist? AB - Confocal laser endomicroscopy (CLE) permits microscopic visualization of the mucosa during endoscopy at an approximately 1000fold magnification, permitting endoscopists to obtain microscopic analysis during gastroscopy. This can result in optimized diagnosis of diffuse alterations such as gastric atrophy and intestinal metaplasia and may limit the sampling error of untargeted biopsies. It also allows risk stratification prior to endoscopic therapy of neoplastic lesions of the stomach. In these areas, CLE represents a valuable adjunct for targeted histopathology. In addition, CLE allows on-site in vivo imaging, and by this insight into physiologic and pathophysiologic as well as molecular events of the stomach without major artifacts. PMID- 26381305 TI - In vivo identification of pancreatic cystic neoplasms with needle-based confocal laser endomicroscopy. AB - Pancreatic cystic lesions (PCLs) are increasingly identified with the widespread use of imaging modalities. The precise diagnosis of PCLs remains a challenge despite the use of CT, MRI, and EUS-FNA. Confocal laser endomicroscopy (CLE) is a new endoscopic imaging modality that provides real-time, very high magnification images. A smaller CLE probe, which can be passed through a 19-gauge FNA needle, is now available. Needle-based CLE during EUS has recently been examined to evaluate PLCs, and the specific criteria of nCLE for the diagnosis of PLCs have been proposed. PMID- 26381306 TI - Can image-enhanced cholangioscopy distinguish benign from malignant lesions in the biliary duct? AB - A new video peroral cholangioscopy (POCS) has been developed with high-quality digital imaging, and its clinical use has been reported. Additionally, direct peroral cholangioscopy (D-POCS) using an ultraslim endoscope has been proposed recently. To improve the diagnostic yield of POCS or D-POCS, image-enhanced endoscopy has been used in combination. Chromoendoscopy with methylene blue staining (ME), autofluorescence imaging (AFI), and narrow-band imaging (NBI) has been evaluated in biliary tract diseases. Observation of the mucosal structure and vessels is reportedly important for distinguishing non-neoplasms from neoplasms. Therefore, NBI is the most promising tool among image-enhanced endoscopies as it can enhance visualization of the mucosal structure and vessels simultaneously. There are currently few reports that have evaluated the utility of POCS or D-POCS based on pathological findings. Thus, endoscopic findings of the bile duct mucosa have not yet been fully established. At present, POCS-guided biopsy should be carried out. PMID- 26381307 TI - Image-enhanced endoscopy technology in the gastrointestinal tract: what is available? AB - Gastrointestinal malignancy accounts for approximately a fifth of all cancer deaths in the United Kingdom. By the time patients are symptomatic, lesions are often advanced, with limited treatment options available. The development of effective endoscopic therapies means that neoplastic lesions can now be treated with improved patient outcomes. This has led to a paradigm shift, whereby the aim of digestive endoscopy is to identify premalignant conditions or early neoplastic change, in order to make an impact on their natural history. This has necessitated an improvement in imaging techniques in order to identify subtle mucosal changes that may harbour precancerous cells. At present there is an array of available imaging modalities, each with implications on cost, training and lesion detection. Here we describe the scientific rationale behind the major commercially available techniques as well as offering a glimpse at possible future directions. PMID- 26381308 TI - Optical diagnosis of small colorectal polyps during colonoscopy: when to resect and discard? AB - Colonoscopy with polypectomy has been shown to be effective in reducing incidence and mortality from colorectal cancer (CRC). The increase in use of colonoscopy in national bowel cancer screening programmes combined with improved technology has resulted in a large increase in detection of polyps. Most polyps detected at screening colonoscopy are small (<10 mm) or diminutive (<6 mm) and, in particular the latter, have a very small chance of containing advanced features or cancer. The main reason for resecting small adenomas and sending them to histopathology serves to inform on the future surveillance intervals. Being able to diagnose adenomas in vivo would allow for them to be resected and discarded, saving the costs associated with histopathology. Diagnosing distal hyperplastic polyps in vivo would allow for these to be left in situ reducing the risks associated with polypectomy. There are now a number of new technologies that could potentially make optical diagnosis a reality. Resect and discard policy is an attractive concept for patients, gastroenterologists and health service providers and would present an enticing change to current clinical practice. PMID- 26381309 TI - Methods to become a high performer in characterization of colorectal polyp histology. AB - The recent advent of advanced imaging technologies has brought real time characterization of polyp histology to the forefront. This concept of optical diagnosis of diminutive polyp histology can bring about a huge paradigm shift in the management of these lesions. Instead of resecting and sending all the diminutive polyps to pathology, there is the potential to practice "resect and discard" for those predicted to be adenomas and "do not resect" strategy for the recto-sigmoid polyps predicted to be hyperplastic. However, one of the major steps before the clinical implementation of real-time histology can be a reality, will be training endoscopists with varying levels of experience in novel imaging technologies. The two major methods for training include didactic teaching and the computer based method. After the initial training, it is imperative that the endoscopists practice this skill during performance of routine colonoscopy to auto validate and assess their own competency. Both practice and reinforcement can help endoscopists become high performers in the characterization of polyp histology. PMID- 26381310 TI - High-resolution microendoscopy in differentiating neoplastic from non-neoplastic colorectal polyps. AB - Colorectal cancer is one of the leading causes of death worldwide. The progression from adenoma to cancer is a well known phenomenon. Current clinical practice favors colonoscopy as the preferred modality for colorectal cancer screening. Many novel endoscopic technologies are emerging for the purposes of performing "optical biopsy" to allow real-time histologic diagnosis of polyps. High resolution microendoscopy is a low-cost endoscopic technology that has demonstrated high sensitivity and specificity in differentiating neoplastic and non-neoplastic polyps. With the ability to make real-time conclusions based on the endoscopic appearance of polyps, it is becoming increasingly possible to decrease the rate of unnecessary polypectomies and utilize a "resect and discard" strategy to decrease costs of pathology evaluation. Future directions for this technology include surveillance of premalignant conditions such as inflammatory bowel disease. Moreover, the low cost and relative ease of use of this technology lends itself to widespread applicability. PMID- 26381311 TI - Serrated lesions of the colon and rectum: the role of advanced endoscopic imaging. AB - Conventional adenomas were traditionally thought to be the only precursors to colorectal cancer (CRC). Nowadays, also serrated polyps are acknowledged as precursor lesions for CRC, responsible for up to 30% of all CRCs and probably a larger percentage of interval CRCs after colonoscopy. In recent years, much research is being done to unravel the serrated neoplasia pathway. Endoscopic detection of serrated polyps is still a challenge for gastroenterologists, which is illustrated by large variations in detection rates of serrated polyps in the proximal colon. Clinical practice is further inhibited by poor optical differentiation of SSA/Ps from conventional adenomas and HPs and difficult delineation of those lesions, resulting in incomplete resection. The main focus of this review is to highlight recent advancements in endoscopic imaging techniques with regards to detection, differentiation and resection of serrated polyps. PMID- 26381312 TI - Surveillance of long-standing colitis: the role of image-enhanced endoscopy. AB - Patients with long-standing inflammatory bowel disease of the colon are at an increased risk of developing colorectal carcinoma. Surveillance programs have been implemented with the aim of detecting neoplastic lesions in an early stage. Due to limitations of conventional white light endoscopy, several new techniques to enhance the detection of dysplastic lesions in this setting have been explored. These advanced endoscopic techniques use a variety of methods to improve visualization, such as pancolonic dye-spraying (chromoendoscopy), optical filters (narrow-band imaging) and autofluorescence of mucosal tissue (autofluorescence imaging). At present, most guidelines have adopted chromoendoscopy as the preferred method for surveillance, based on several controlled studies. It is currently unknown if widespread implementation of chromoendoscopy will lead to an improved clinical outcome. This review explores the current evidence on image-enhanced endoscopic techniques used in the detection of neoplastic lesions in patients with long standing colitis. PMID- 26381313 TI - Pluripotent stem cell based gene therapy for hematological diseases. AB - Standard treatment for severe inherited hematopoietic diseases consists of allogeneic stem cell transplantation. Alternatively, patients can be treated with gene therapy: gene-corrected autologous hematopoietic stem and progenitor cells (HSPC) are transplanted. By using retro- or lentiviral vectors, a copy of the functional gene is randomly inserted in the DNA of the HSPC and becomes constitutively expressed. Gene therapy is currently limited to monogenic diseases for which clinical trials are being actively conducted in highly specialized centers around the world. This approach, although successful, carries with it inherent safety and efficacy issues. Recently, two technologies became available that, when combined, may enable treatment of genetic defects by HSPC that have the non-functional allele replaced by a functional copy. One technology consists of the generation of induced pluripotent stem cells (iPSC) from patient blood samples or skin biopsies, the other concerns nuclease-mediated gene editing. Both technologies have been successfully combined in basic research and appear applicable in the clinic. This paper reviews recent literature, discusses what can be achieved in the clinic using present knowledge and points out further research directions. PMID- 26381314 TI - National estimates of Australian gambling prevalence: f indings from a dual-frame omnibus survey. AB - BACKGROUND, AIMS AND DESIGN: The increase in mobile telephone-only households may be a source of bias for traditional landline gambling prevalence surveys. Aims were to: (1) identify Australian gambling participation and problem gambling prevalence using a dual-frame (50% landline and 50% mobile telephone) computer assisted telephone interviewing methodology; (2) explore the predictors of sample frame and telephone status; and (3) explore the degree to which sample frame and telephone status moderate the relationships between respondent characteristics and problem gambling. SETTING AND PARTICIPANTS: A total of 2000 adult respondents residing in Australia were interviewed from March to April 2013. MEASUREMENTS: Participation in multiple gambling activities and Problem Gambling Severity Index (PGSI). FINDINGS: Estimates were: gambling participation [63.9%, 95% confidence interval (CI) = 61.4-66.3], problem gambling (0.4%, 95% CI = 0.2-0.8), moderate risk gambling (1.9%, 95% CI = 1.3-2.6) and low-risk gambling (3.0%, 95% CI = 2.2 4.0). Relative to the landline frame, the mobile frame was more likely to gamble on horse/greyhound races [odds ratio (OR) = 1.4], casino table games (OR = 5.0), sporting events (OR = 2.2), private games (OR = 1.9) and the internet (OR = 6.5); less likely to gamble on lotteries (OR = 0.6); and more likely to gamble on five or more activities (OR = 2.4), display problem gambling (OR = 6.4) and endorse PGSI items (OR = 2.4-6.1). Only casino table gambling (OR = 2.9) and internet gambling (OR = 3.5) independently predicted mobile frame membership. Telephone status (landline frame versus mobile dual users and mobile-only users) displayed similar findings. Finally, sample frame and/or telephone status moderated the relationship between gender, relationship status, health and problem gambling (OR = 2.9-7.6). CONCLUSION: Given expected future increases in the mobile telephone only population, best practice in population gambling research should use dual frame sampling methodologies (at least 50% landline and 50% mobile telephone) for telephone interviewing. PMID- 26381315 TI - Light-Induced Indeterminacy Alters Shade-Avoiding Tomato Leaf Morphology. AB - Plants sense the foliar shade of competitors and alter their developmental programs through the shade-avoidance response. Internode and petiole elongation, and changes in overall leaf area and leaf mass per area, are the stereotypical architectural responses to foliar shade in the shoot. However, changes in leaf shape and complexity in response to shade remain incompletely, and qualitatively, described. Using a meta-analysis of more than 18,000 previously published leaflet outlines, we demonstrate that shade avoidance alters leaf shape in domesticated tomato (Solanum lycopersicum) and wild relatives. The effects of shade avoidance on leaf shape are subtle with respect to individual traits but are combinatorially strong. We then seek to describe the developmental origins of shade-induced changes in leaf shape by swapping plants between light treatments. Leaf size is light responsive late into development, but patterning events, such as stomatal index, are irrevocably specified earlier. Observing that shade induces increases in shoot apical meristem size, we then describe gene expression changes in early leaf primordia and the meristem using laser microdissection. We find that in leaf primordia, shade avoidance is not mediated through canonical pathways described in mature organs but rather through the expression of KNOTTED1 LIKE HOMEOBOX and other indeterminacy genes, altering known developmental pathways responsible for patterning leaf shape. We also demonstrate that shade induced changes in leaf primordium gene expression largely do not overlap with those found in successively initiated leaf primordia, providing evidence against classic hypotheses that shaded leaf morphology results from the prolonged production of juvenile leaf types. PMID- 26381317 TI - Unexpected bowel perforation in Wegener's granulomatosis. PMID- 26381316 TI - The Rice E3-Ubiquitin Ligase HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENE1 Modulates the Expression of ROOT MEANDER CURLING, a Gene Involved in Root Mechanosensing, through the Interaction with Two ETHYLENE-RESPONSE FACTOR Transcription Factors. AB - Plant roots can sense and respond to a wide diversity of mechanical stimuli, including touch and gravity. However, little is known about the signal transduction pathways involved in mechanical stimuli responses in rice (Oryza sativa). This work shows that rice root responses to mechanical stimuli involve the E3-ubiquitin ligase rice HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENE1 (OsHOS1), which mediates protein degradation through the proteasome complex. The morphological analysis of the roots in transgenic RNA interference::OsHOS1 and wild-type plants, exposed to a mechanical barrier, revealed that the OsHOS1 silencing plants keep a straight root in contrast to wild-type plants that exhibit root curling. Moreover, it was observed that the absence of root curling in response to touch can be reverted by jasmonic acid. The straight root phenotype of the RNA interference::OsHOS1 plants was correlated with a higher expression rice ROOT MEANDER CURLING (OsRMC), which encodes a receptor-like kinase characterized as a negative regulator of rice root curling mediated by jasmonic acid. Using the yeast two-hybrid system and bimolecular fluorescence complementation assays, we showed that OsHOS1 interacts with two ETHYLENE RESPONSE FACTOR transcription factors, rice ETHYLENE-RESPONSIVE ELEMENT BINDING PROTEIN1 (OsEREBP1) and rice OsEREBP2, known to regulate OsRMC gene expression. In addition, we showed that OsHOS1 affects the stability of both transcription factors in a proteasome-dependent way, suggesting that this E3-ubiquitin ligase targets OsEREBP1 and OsEREBP2 for degradation. Our results highlight the function of the proteasome in rice response to mechanical stimuli and in the integration of these signals, through hormonal regulation, into plant growth and developmental programs. PMID- 26381318 TI - Current concepts in the prevention of pathogen transmission via blood/plasma derived products for bleeding disorders. AB - The pathogen safety of blood/plasma-derived products has historically been a subject of significant concern to the medical community. Measures such as donor selection and blood screening have contributed to increase the safety of these products, but pathogen transmission does still occur. Reasons for this include lack of sensitivity/specificity of current screening methods, lack of reliable screening tests for some pathogens (e.g. prions) and the fact that many potentially harmful infectious agents are not routinely screened for. Methods for the purification/inactivation of blood/plasma-derived products have been developed in order to further reduce the residual risk, but low concentrations of pathogens do not necessarily imply a low level of risk for the patient and so the overall challenge of minimising risk remains. This review aims to discuss the variable level of pathogenic risk and describes the current screening methods used to prevent/detect the presence of pathogens in blood/plasma-derived products. PMID- 26381319 TI - Family history of skin cancer is associated with early-onset basal cell carcinoma independent of MC1R genotype. AB - BACKGROUND: As a marker of genetic susceptibility and shared lifestyle characteristics, family history of cancer is often used to evaluate an individual's risk for developing a particular malignancy. With comprehensive data on pigment characteristics, lifestyle factors, and melanocortin 1 receptor (MC1R) gene sequence, we sought to clarify the role of family history of skin cancer in early-onset basal cell carcinoma (BCC). MATERIALS AND METHODS: Early onset BCC cases (n=376) and controls with benign skin conditions (n=383) under age 40 were identified through Yale dermatopathology. Self-report data on family history of skin cancer (melanoma and non-melanoma skin cancer), including age of onset in relatives, was available from a structured interview. Participants also provided saliva samples for sequencing of MC1R. RESULTS: A family history of skin cancer was associated with an increased risk of early-onset BCC (OR 2.49, 95% CI 1.80 3.45). In multivariate models, family history remained a strong risk factor for early-onset BCC after adjustment for pigment characteristics, UV exposure, and MC1R genotype (OR 2.41, 95% CI 1.74-3.35). CONCLUSIONS: Risk for BCC varied based upon the type and age of onset of skin cancer among affected relatives; individuals with a first-degree relative diagnosed with skin cancer prior to age 50 were at highest risk for BCC (OR 4.79, 95% CI 2.90-7.90). Even after taking into account potential confounding effects of MC1R genotype and various lifestyle factors that close relatives may share, family history of skin cancer remained strongly associated with early-onset BCC. PMID- 26381320 TI - [Benefit of clean intermittent self-catheterization in the management of urethral strictures]. AB - OBJECTIVES: Urethral stenosis has a recurrent character. The urethroplasty is often proposed for repeat stenosis. This study seeks to explore the interest of clean intermittent self-catheterization in the evolution of urethral stenosis after urethrotomy. METHODS: Single-center retrospective study from 2008 to 2013, concerning patients who received urethrotomy to treat urethral stenosis which was confirmed by endoscopy and a flow chart. Some accomplished self-catheterization in addition to urethrotomy to prevent recurrence. The monitoring was provided during consultation by a subjective assessment (patient and surgeon) and a flow chart. The restenosis were confirmed by endoscopy and flow chart. RESULTS: Ninety three patients treated with urethrotomy alone (50 patients) or associated with self-catheterization (43) was included. Urethral stenosis were mostly iatrogenic (75%), short <10mm (84%), single (74%) and primary (50.5%). Mean follow-up was 99.3+/-72.8 weeks. Eighteen patients (19%) had symptomatic recurrence suspected by flow chart with a mean Qmax at recurrence was 6.25+/-2.8mL/s (P<0.001), 8 in urethrotomy group and 10 in the urethrotomy+self-catheterization group. Recurrence rates were comparable in the 2 groups, urethrotomy (16%) urethrotomy+self-catheterization (23%) (P=0.46). The mean time to recurrence was 81.1+/-87 weeks and was different in the 2 groups: 76.8+/-76.3 weeks in urethrotomy group, 83.3+/-93.9 in urethrotomy+self-catheterization group (P=0.014). An analysis recurrence for the primitive urethral stenosis showed that the recurrence rate was not statistically different: 18% for urethrotomy+self catheterization group vs 14% for urethrotomy group. An analysis of recurrent relapses for urethral stenosis showed a rate of 26%, comparable in the 2 groups (P=1). CONCLUSION: After urethrotomy, urethral stenosis recurs in 1 patient over 5, after 18 months especially if they were complicated (multiple, recurrent, extended). Self-catheterization do not provide benefit in terms of recurrence (for the general population and for primitive urethral stenosis) compared to only urethrotomy but seem to extend the time without recurrence (76.8 weeks vs 83.3 weeks). LEVEL OF EVIDENCE: 5. PMID- 26381321 TI - A mild case of giant axonal neuropathy without central nervous system manifestation. AB - An 11-year-old boy presented with progressive walking disturbances. He exhibited severe equinovarus feet that together presented with hyperreflexia of the patellar tendon and extensor plantar, resembling spastic paraplegia or upper neuron disease. He showed mild distal muscle atrophy, as well. We did not observe signs of cognitive impairment, cerebellar signs, or brain magnetic resonance imaging abnormalities. Nerve biopsy showed giant axon swellings filled with neurofilaments. Gene analysis revealed novel compound heterozygous missense mutations in the gigaxonin gene, c.808G>A (p.G270S) and c.1727C>A (p.A576E). He was diagnosed with mild giant axonal neuropathy (GAN) without apparent central nervous system involvement. Patients with classical GAN manifest their symptoms during early childhood. Mild GAN, particularly in early stages, can be misdiagnosed because of lack of typical hair features and incomplete or indistinct peripheral and central nervous system symptoms. This case is important since it can aid to identify atypical and milder clinical courses of GAN. This report widens the mild GAN clinical spectrum, alerting physicians for correct diagnosis. PMID- 26381322 TI - Cap-dependent, scanning-free translation initiation mechanisms. AB - Eukaryotic translation initiation is an intricate and multi-step process that includes 43S Pre-Initiation Complex (PIC) assembly, attachment of the PIC to the mRNA, scanning, start codon selection and 60S subunit joining. Translation initiation of most mRNAs involves recognition of a 5'end m7G cap and ribosomal scanning in which the 5' UTR is checked for complementarity with the AUG. There is however an increasing number of mRNAs directing translation initiation that deviate from the predominant mechanism. In this review we summarize the canonical translation initiation process and describe non-canonical mechanisms that are cap dependent but operate without scanning. In particular we focus on several examples of translation initiation driven either by mRNAs with extremely short 5' leaders or by highly complex 5' UTRs that promote ribosome shunting. PMID- 26381323 TI - Insight into lncRNA biology using hybridization capture analyses. AB - Despite mounting evidence of the importance of large non-coding RNAs (lncRNAs) in biological regulation, we still know little about how these lncRNAs function. One approach to understand the function of lncRNAs is to biochemically purify endogenous lncRNAs from fixed cells using complementary oligonucleotides. These hybridization capture approaches can reveal the genomic localization of lncRNAs, as well as the proteins and RNAs with which they interact. To help researchers understand how these tools can uncover lncRNA function, this review discusses the considerations and influences of different parameters, (e.g., crosslinking reagents, oligonucleotide chemistry and hybridization conditions) and controls to avoid artifacts. By examining the application of these tools, this review will highlight the progress and pitfalls of studying lncRNAs using hybridization capture approaches.This article is part of a Special Issue entitled: Clues to long noncoding RNA taxonomy1, edited by Dr. Tetsuro Hirose and Dr. Shinichi Nakagawa. PMID- 26381324 TI - Prebiotic preferences of human lactobacilli strains in co-culture with bifidobacteria and antimicrobial activity against Clostridium difficile. AB - AIM: To evaluate robustness, prebiotic utilization of Lactobacillus paracasei F8 and Lactobacillus plantarum F44 in mono- and co-cultures with Bifidobacterium breve 46 and Bifidobacterium animalis sub sp. lactis 8 : 8 and antimicrobial activity of co-culture against Clostridium difficile. METHODS AND RESULTS: The two Lactobacillus strains showed a high acid and bile tolerance. Lactobacillus plantarum F44 showed maximum growth in de Man Rogosa Sharpe basal broth with glucose and lactulose compared to growth in galacto-oligosaccharides (GOS) and isomalto-oligosaccharides (IMOS). In co-culture system, the amylolytic Bif. breve 46 stimulated the growth of a nonamylolytic Lact. paracasei F8, probably by producing intermediate metabolites of starch metabolism. A higher growth of four strains Lact. paracasei F8, Lact. plantarum F44, Bif. breve 46 and Bif. animalis ssp lactis 8 : 8 with different prebiotic combinations was found in a MRSC basal broth with SS (soluble starch) + IMOS + GOS and IMOS + GOS respectively. The two Lactobacillus strains exhibited a high antimicrobial activity against four clinical Cl. difficile strains and a hypervirulent NAP1/027strain and suppressed the toxin titres possibly through the production of organic acids and heat stable antimicrobial proteins when grown on glucose and through the production of acids when grown on prebiotics. Culture supernatants from synbiotic combinations inhibited the growth of the Cl. difficile NAP1/027 strain and its toxin titres. CONCLUSION: Lactobacillus paracasei F8, Lact. plantarum F44 exhibited potential probiotic properties. Further, the two Lactobacillus and two bifidobacteria strains were compatible with each other and exhibited high growth in co-cultures in presence of prebiotics and SS and antimicrobial activity against clinical Cl. difficile strains and a hypervirulent NAPI/027 strain. SIGNIFICANCE AND IMPACT OF THE STUDY: Results are promising for the development of a multi-strain synergistic synbiotic supplement for protection against Cl. difficile infection. PMID- 26381325 TI - Early and Intermediate Results of Elective Endovascular Treatment of True Visceral Artery Aneurysms. AB - BACKGROUND: To retrospectively analyze early and follow-up results of endovascular management of visceral artery aneurysms (VAAs) in a single-center experience. METHODS: From 2007 to June 2013, 26 consecutive elective endovascular interventions for VAAs were performed in 26 patients; preoperative, intraoperative, and postoperative data were prospectively collected in a dedicated database. Early (<30 days) and follow-up results were evaluated. RESULTS: The site of aneurysm was splenic artery in 17 patients, common hepatic artery in 3 patients, renal artery and pancreaticoduodenal artery in 2 cases each, and gastroduodenal artery and celiac trunk in one case each. All the lesions were asymptomatic, and the mean diameter was 22.8 mm. Interventions consisted in coiling in 19 cases; in 4 patients a covered stent was placed, whereas the remaining 3 patients had a multilayer stent. Technical success was 89%. There were no perioperative deaths; 1 patient with splenic artery aneurysm had coils migration with symptomatic splenic infarction and underwent successful redo coils packing. Median duration of follow-up was 18 months. During follow-up, 1 aneurysm-unrelated death occurred. One asymptomatic thrombosis of a treated vessel was recorded, with a 2-year estimated patency rate of 91%. Mean aneurysmal diameter at the latest follow-up was 20.2 mm (P = 0.001 in comparison with preoperative values; 95% confidence interval 1.9-5.2). Complete exclusion of the aneurysm occurred in all but 1 patient, who had a limited increasing in the diameter of its splenic aneurysmal sac after coiling. Another patient developed a more distal aneurysm of the splenic artery after 24 months. No reinterventions were required. Freedom from aneurysm-related complications at 2 years was 72.9% (Standard Error, 0.09). CONCLUSIONS: In our experience, endovascular treatment of VAA, when feasible, provided excellent perioperative results with low rates of complications and reinterventions. Even if the risk of developing aneurysm related complications during follow-up is substantial, most of them can be watched without the need for repeated interventions. PMID- 26381326 TI - "Caval Reconstruction for Lower-Extremity Sarcoma Metastasis Trapped within Inferior Vena Cava Filter". AB - This report describes the management of a hematogenously spread metastasis from a lower-extremity sarcoma found trapped within an inferior vena cava (IVC) filter. Although endovascular techniques for treating thrombosed IVC filters are successful in a majority of cases, the malignant nature of this lesion required a novel approach. In this unique case, the segment of infrarenal IVC with the thrombosed filter was resected and reconstruction performed with an interposition prosthetic graft. There were no early or late complications, and the patient remains clinically free of recurrence at 24-month follow-up. PMID- 26381327 TI - Genetics, Pregnancy, and Aortic Degeneration. AB - We present a case of familial thoracic aortic aneurysm and dissection (FTAAD) in a pregnant female. FTAAD is an inherited, nonsyndromic aortopathy resulting from several genetic mutations critical to aortic wall integrity have been identified. One such mutation is the myosin heavy chain gene (MYH11) which is responsible for 1-2% of all FTAAD cases. This mutation results in aortic medial degeneration, loss of elastin, and reticulin fiber fragmentation predisposing to TAAD. Aortic disease is more aggressive during pregnancy as a result of increased wall stress from hyperdynamic cardiovascular changes and estrogen-induced aortic media degeneration. Our patient was a 29-year-old G2P1 woman at 26 weeks gestation presenting with abdominal and back pain. Work-up revealed a 6.4-cm ascending aortic aneurysm with a type A dissection extending into all arch vessels, aortic coarctation at the isthmus, and a separate focal type B aortic dissection with visceral involvement. Surgical management included concomitant cesarean section with delivery of a live premature infant, tubal ligation, ascending aortic replacement with reconstruction of the arch vessels, and aortic valve resuspension. The type B dissection was managed medically without complication. This is the first reported case of aortic dissection in a patient with FTAAD/MYH11 mutation and pregnancy. This case highlights that FTAAD and pregnancy cause aortic degeneration via distinct mechanisms and that hyperdynamics of pregnancy increase aortic wall stress. Management of pregnancy associated with aortopathy requires early transfer to a tertiary center, careful investigation to identify familial aortopathy, fetal monitoring, and a multidisciplinary team approach. PMID- 26381328 TI - Persistent high fever for more than 10 days during acute phase is a risk factor for endothelial dysfunction in children with a history of Kawasaki disease. AB - BACKGROUND: Endothelial dysfunction has previously been reported in children with a history of Kawasaki disease, but the determinants of endothelial function in Kawasaki disease patients are still unknown. In this study, we investigated endothelial function in Kawasaki disease patients and attempted to identify risk factors for persistent endothelial dysfunction. METHODS: Using high-resolution ultrasound, we measured the percent flow-mediated dilatation, an arterial response to reactive hyperemia, to evaluate endothelial function in 67 patients with a history of Kawasaki disease and 28 age- and sex-matched control subjects. We divided the Kawasaki disease patients into a group with impaired endothelial function (the percent flow-mediated dilatation below -2 standard deviations of the control group) and a group with normal endothelial function (the percent flow mediated dilatation more than -2 standard deviations of control). Logistic multiple regression analysis was performed to identify independent predictors of impaired endothelial function. RESULTS: In Kawasaki disease patients, the percent flow-mediated dilatation was significantly lower than in the control subjects (9.8+/-3.6%, compared with 13.1+/-3.4%, p<0.01). In 13 Kawasaki disease patients (3 patients with coronary artery lesions and 10 patients without coronary artery lesions), the percent flow-mediated dilatation was below -2 standard deviations of control. Logistic multiple regression analysis showed that a febrile period of longer than 10 days during the acute phase was the significant risk factor for endothelial dysfunction (odds ratio: 8.562; 95% confidence interval: 1.366 53.68). Presence of coronary artery lesions was not a determinant of endothelial dysfunction. CONCLUSIONS: Systemic endothelial dysfunction exists in children with a history of Kawasaki disease, and a febrile period of longer than 10 days during the acute phase is an independent predictor of endothelial dysfunction irrespective of coronary artery involvement. PMID- 26381329 TI - Medium-term follow-up of renal function in hypoxaemic congenital heart disease patients. AB - Introduction Hypoxaemic congenital heart disease (CHD) patients are at higher risk of complications. The aim of this study was to compare and follow-up blood and 24-hour urine analytical data in hypoxaemic and non-hypoxaemic CHD patients. METHODS: The inclusion criteria for this study were as follows: patients older than 14 years of age with a structural CHD with or without associated hypoxaemia. RESULTS: In total, 27 hypoxaemic and 48 non-hypoxaemic CHD patients were included in order to compare blood and 24-hour urine analytical data. Among hypoxaemic patients, 13 (48.1%) were male, two (7.4%) had diabetes mellitus, one of whom was a smoker, one (3.7%) had systemic arterial hypertension, and 11 (40.7%) showed pulmonary arterial hypertension. The mean follow-up time was 3.1+/-1.9 years. Hypoxaemic CHD patients showed higher proteinuria concentrations (g/24 hours) (0.09 (0.07; 0.46) versus 0.08 (0.07; 0.1), p=0.054) and 24-hour albumin excretion rate (ug/min) (16.5 (11.2; 143.5) versus 4.4 (0.0; 7.6), p<0.001) compared with non-hypoxaemic CHD patients; however, no significant differences were found in the proteinuria levels and in the 24-hour albumin excretion rate in CHD patients with associated hypoxaemia, both at baseline and at follow-up. When divided into groups, hypoxaemic patients with palliative shunts showed significantly higher proteinuria concentrations compared with hypoxaemic patients not operated on or with Fontan procedures (p=0.01). No significant differences were seen in 24-hour proteinuria and 24-hour albumin excretion rate during the follow-up of patients with palliative shunts. CONCLUSIONS: Hypoxaemic CHD patients have significant higher 24-hour proteinuria concentration and 24-hour albumin excretion rate compared with non-hypoxaemic CHD patients. Among hypoxaemic CHD patients, those with palliative shunts showed the highest 24-hour proteinuria concentrations. PMID- 26381330 TI - Imidazotriazines: Spleen Tyrosine Kinase (Syk) Inhibitors Identified by Free Energy Perturbation (FEP). AB - There has been significant interest in spleen tyrosine kinase (Syk) owing to its role in a number of disease states, including autoimmunity, inflammation, and cancer. Ongoing therapeutic programs have resulted in several compounds that are now in clinical use. Herein we report our optimization of the imidazopyrazine core scaffold of Syk inhibitors through the use of empirical and computational approaches. Free-energy perturbation (FEP) methods with MCPRO+ were undertaken to calculate the relative binding free energies for several alternate scaffolds. FEP was first applied retrospectively to determine if there is any predictive value; this resulted in 12 of 13 transformations being predicted in a directionally correct manner. FEP was then applied in a prospective manner to evaluate 17 potential targets, resulting in the realization of imidazotriazine 17 (3-(4-(3,4 dimethoxyphenylamino)imidazo[1,2-f][1,2,4]triazin-2-yl)benzamide), which shows a tenfold improvement in activity relative to the parent compound and no increase in atom count. Optimization of 17 led to compounds with nanomolar cellular activity. PMID- 26381331 TI - Towards quantitative, atomic-resolution reconstruction of the electrostatic potential via differential phase contrast using electrons. AB - Differential phase contrast images in scanning transmission electron microscopy can be directly and quantitatively related to the gradient of the projected specimen potential provided that (a) the specimen can be treated as a phase object and (b) full 2D diffraction patterns as a function of probe position can be obtained. Both are challenging to achieve in atomic resolution imaging. The former is fundamentally limited by probe spreading and dynamical electron scattering, and we explore its validity domain in the context of atomic resolution differential phase contrast imaging. The latter, for which proof-of principle experimental data sets exist, is not yet routine. We explore the extent to which more established segmented detector geometries can instead be used to reconstruct a quantitatively good approximation to the projected specimen potential. PMID- 26381332 TI - Nano-architecture of gustatory chemosensory bristles and trachea in Drosophila wings. AB - In the Drosophila wing anterior margin, the dendrites of gustatory neurons occupy the interior of thin and long bristles that present tiny pores at their extremities. Many attempts to measure ligand-evoked currents in insect wing gustatory neurons have been unsuccessful for technical reasons. The functions of this gustatory activity therefore remain elusive and controversial. To advance our knowledge on this understudied tissue, we investigated the architecture of the wing chemosensory bristles and wing trachea using Raman spectroscopy and fluorescence microscopy. We hypothesized that the wing gustatory hair, an open ended capillary tube, and the wing trachea constitute biological systems similar to nano-porous materials. We present evidence that argues in favour of the existence of a layer or a bubble of air beneath the pore inside the gustatory hair. We demonstrate that these hollow hairs and wing tracheal tubes fulfil conditions for which the physics of fluids applied to open-ended capillaries and porous materials are relevant. We also document that the wing gustatory hair and tracheal architectures are capable of trapping volatile molecules from the environment, which might increase the efficiency of their spatial detection by way of wing vibrations or during flight. PMID- 26381334 TI - The Opportunities of Interprofessional Education. PMID- 26381333 TI - miR-34/449 control apical actin network formation during multiciliogenesis through small GTPase pathways. AB - Vertebrate multiciliated cells (MCCs) contribute to fluid propulsion in several biological processes. We previously showed that microRNAs of the miR-34/449 family trigger MCC differentiation by repressing cell cycle genes and the Notch pathway. Here, using human and Xenopus MCCs, we show that beyond this initial step, miR-34/449 later promote the assembly of an apical actin network, required for proper basal bodies anchoring. Identification of miR-34/449 targets related to small GTPase pathways led us to characterize R-Ras as a key regulator of this process. Protection of RRAS messenger RNA against miR-34/449 binding impairs actin cap formation and multiciliogenesis, despite a still active RhoA. We propose that miR-34/449 also promote relocalization of the actin binding protein Filamin-A, a known RRAS interactor, near basal bodies in MCCs. Our study illustrates the intricate role played by miR-34/449 in coordinating several steps of a complex differentiation programme by regulating distinct signalling pathways. PMID- 26381335 TI - Improving Orientation Outcomes: Implementation of Phased Orientation Process in an Intermediate Special Care Nursery. AB - In response to changing needs of registered nurse orientees, the staff education committee in the Intermediate Special Care Nursery has implemented a phased orientation process. This phased process includes a mentoring experience postorientation to support a new nurse through the first year of employment. Since implementing the phased orientation process in the Intermediate Special Care Nursery, orientee satisfaction and preparation to practice have increased, and length of orientation has decreased. PMID- 26381336 TI - Non-Critical-Care Nurses' Perceptions of Facilitators and Barriers to Rapid Response Team Activation. AB - Rapid response teams can save lives but are only effective when activated. We surveyed 50 nurses for their perceptions of facilitators and barriers to activation. Findings showed that participants need more education on their role and when to activate the rapid response team. Nurses who comprise the team need help building their communication skills. We recommend nursing professional development specialists increase the frequency of offerings and expand the focus on roles, activation criteria, and communication skills. PMID- 26381337 TI - Caring in Nursing Professional Development. AB - Caring science has been identified and examined in the discipline of nursing for over 40 years. Within this period, the topic has been analyzed and studied resulting in theories, models, books, and articles published nationally and internationally. Although advancements have been made in caring knowledge development, opportunities to integrate caring science into all aspects of nursing abound, including the specialty of nursing professional development. The focus of this article is to present ways in which nursing professional development specialists may incorporate caring science into practice, using Ray's (2010) Transcultural Caring Dynamics in Nursing and Health Care model as an exceptional exemplar for understanding, awareness, and choice for nurses and patients. PMID- 26381338 TI - New Rural Acute Care Nurses Speak Up: "We're it" But We're Not Ready. AB - Many novice registered nurses feel ill-prepared for rural nursing practice. Using a mixed method design, an assessment of the learning needs of new graduate nurses (NGNs) working in rural hospitals in Alberta, Canada, was undertaken. NGNs in rural practice indicated that they struggle with becoming "multispecialists." Consequently, administrators and nurse educators need to tailor workplace structures by establishing collaborative programs with urban facilities and using orientation tailored to the learning needs of NGNs. PMID- 26381339 TI - The Lasater Clinical Judgment Rubric as a Framework to Enhance Clinical Judgment in Novice and Experienced Nurses. AB - Clinical judgment has been identified as a critical component of professional nursing practice and enables nurses to deliver safe patient care with optimal outcomes. Nurses, particularly those transitioning into clinical practice, may require assistance to enhance their clinical judgment skills. This article presents the Lasater Clinical Judgment Rubric, which has primarily been used in the academic setting, as a framework for nursing professional development specialists to enhance the clinical judgment skills of novice and experienced nurses. PMID- 26381340 TI - Nursing Professional Development Specialists as Role Models. PMID- 26381341 TI - National Accreditation Standards for Nurse Residency Programs, Part 1. PMID- 26381342 TI - Incorporating Appreciative Inquiry Into Your Teaching Tool Kit. PMID- 26381343 TI - Interprofessional Simulation: Prioritizing Interprofessional Competencies to Improve Patient Outcomes. PMID- 26381345 TI - Lead, Do Not Follow. PMID- 26381346 TI - The Effect of Instructional Method on Cardiopulmonary Resuscitation Skill Performance: A Comparison Between Instructor-Led Basic Life Support and Computer Based Basic Life Support With Voice-Activated Manikin. AB - Validating participants' ability to correctly perform cardiopulmonary resuscitation (CPR) skills during basic life support courses can be a challenge for nursing professional development specialists. This study compares two methods of basic life support training, instructor-led and computer-based learning with voice-activated manikins, to identify if one method is more effective for performance of CPR skills. The findings suggest that a computer-based learning course with voice-activated manikins is a more effective method of training for improved CPR performance. PMID- 26381349 TI - Genetic control of obesity, glucose homeostasis, dyslipidemia and fatty liver in a mouse model of diet-induced metabolic syndrome. AB - BACKGROUND/OBJECTIVES: Both genetic and dietary factors contribute to the metabolic syndrome (MetS) in humans and animal models. Characterizing their individual roles as well as relationships among these factors is critical for understanding MetS pathogenesis and developing effective therapies. By studying phenotypic responsiveness to high-risk versus control diet in two inbred mouse strains and their derivatives, we estimated the relative contributions of diet and genetic background to MetS, characterized strain-specific combinations of MetS conditions, and tested genetic and phenotypic complexity on a single substituted chromosome. METHODS: Ten measures of metabolic health were assessed in susceptible C57BL/6 J and resistant A/J male mice fed either a control or a high-fat, high-sucrose (HFHS) diet, permitting estimates of the relative influences of strain, diet and strain-diet interactions for each trait. The same traits were measured in a panel of C57BL/6 J (B6)-Chr(A/J) chromosome substitution strains (CSSs) fed the HFHS diet, followed by characterization of interstrain relationships, covariation among metabolic traits and quantitative trait loci (QTLs) on Chromosome 10. RESULTS: We identified significant genetic contributions to nine of ten metabolic traits and significant dietary influence on eight. Significant strain-diet interaction effects were detected for four traits. Although a range of HFHS-induced phenotypes were observed among the CSSs, significant associations were detected among all traits but one. Strains were grouped into three clusters based on overall phenotype and specific CSSs were identified with distinct and reproducible trait combinations. Finally, several Chr10 regions were shown to control the severity of MetS conditions. CONCLUSIONS: Generally strong genetic and dietary effects validate these CSSs as a multifactorial model of MetS. Although traits tended to segregate together, considerable phenotypic heterogeneity suggests that underlying genetic factors influence their co-occurrence and severity. Identification of multiple QTLs within and among strains highlights both the complexity of genetically regulated, diet-induced MetS and the ability of CSSs to prioritize candidate loci for mechanistic studies. PMID- 26381348 TI - Behavioral predictors of attrition in adolescents participating in a multidisciplinary obesity treatment program: EVASYON study. AB - The aims of this study were to identify the cognitive and behavioral predictors of dropping out and to estimate the attrition rate during different phases of an intervention program to treat overweight and obesity in adolescents. Overweight/obese adolescents (n=156, aged: 13-16 years; 71 male and 85 female subjects) were included in a multicomponent (diet, physical activity and psychological support) family-based group treatment program. At baseline and after 2 months (intensive phase) and 13 months (extensive phase) of follow-up, we measured adolescents' cognitive and behavioral dimensions, together with the parents' perception of their child's behavior. Of the 156 adolescents selected, 112 completed the full program (drop-out rate of 28.2%). The risk of dropping out during the extensive phase increased by 20% for each unit increase in the adolescent's social insecurity score (odds ratio=1.20, 95% confidence interval=1.07-1.34, P=0.002). The adolescents who had a high interoceptive awareness showed a significant decrease of 13.0% in the probability of dropping out (odds ratio=0.87, 95% confidence interval=0.77-0.99, P=0.040). Adolescents' social insecurity was the main predictor of drop-out in a multicomponent family group-based obesity treatment program. To reduce attrition rates in these programs, the individual's social insecurity level needs to be reduced, whereas the family's awareness of eating-related behavior needs adjustment. PMID- 26381350 TI - Highly efficient CRISPR/Cas9-mediated transgene knockin at the H11 locus in pigs. AB - Transgenic pigs play an important role in producing higher quality food in agriculture and improving human health when used as animal models for various human diseases in biomedicine. Production of transgenic pigs, however, is a lengthy and inefficient process that hinders research using pig models. Recent applications of the CRISPR/Cas9 system for generating site-specific gene knockout/knockin models, including a knockout pig model, have significantly accelerated the animal model field. However, a knockin pig model containing a site-specific transgene insertion that can be passed on to its offspring remains lacking. Here, we describe for the first time the generation of a site-specific knockin pig model using a combination of CRISPR/Cas9 and somatic cell nuclear transfer. We also report a new genomic "safe harbor" locus, named pH11, which enables stable and robust transgene expression. Our results indicate that our CRISPR/Cas9 knockin system allows highly efficient gene insertion at the pH11 locus of up to 54% using drug selection and 6% without drug selection. We successfully inserted a gene fragment larger than 9 kb at the pH11 locus using the CRISPR/Cas9 system. Our data also confirm that the gene inserted into the pH11 locus is highly expressed in cells, embryos and animals. PMID- 26381351 TI - In vivo Monitoring of Transcriptional Dynamics After Lower-Limb Muscle Injury Enables Quantitative Classification of Healing. AB - Traumatic lower-limb musculoskeletal injuries are pervasive amongst athletes and the military and typically an individual returns to activity prior to fully healing, increasing a predisposition for additional injuries and chronic pain. Monitoring healing progression after a musculoskeletal injury typically involves different types of imaging but these approaches suffer from several disadvantages. Isolating and profiling transcripts from the injured site would abrogate these shortcomings and provide enumerative insights into the regenerative potential of an individual's muscle after injury. In this study, a traumatic injury was administered to a mouse model and healing progression was examined from 3 hours to 1 month using high-throughput RNA-Sequencing (RNA-Seq). Comprehensive dissection of the genome-wide datasets revealed the injured site to be a dynamic, heterogeneous environment composed of multiple cell types and thousands of genes undergoing significant expression changes in highly regulated networks. Four independent approaches were used to determine the set of genes, isoforms, and genetic pathways most characteristic of different time points post injury and two novel approaches were developed to classify injured tissues at different time points. These results highlight the possibility to quantitatively track healing progression in situ via transcript profiling using high- throughput sequencing. PMID- 26381352 TI - Modulation of GABA and resting state functional connectivity by transcranial direct current stimulation. AB - We previously demonstrated that network level functional connectivity in the human brain could be related to levels of inhibition in a major network node at baseline (Stagg et al., 2014). In this study, we build upon this finding to directly investigate the effects of perturbing M1 GABA and resting state functional connectivity using transcranial direct current stimulation (tDCS), a neuromodulatory approach that has previously been demonstrated to modulate both metrics. FMRI data and GABA levels, as assessed by Magnetic Resonance Spectroscopy, were measured before and after 20 min of 1 mA anodal or sham tDCS. In line with previous studies, baseline GABA levels were negatively correlated with the strength of functional connectivity within the resting motor network. However, although we confirm the previously reported findings that anodal tDCS reduces GABA concentration and increases functional connectivity in the stimulated motor cortex; these changes are not correlated, suggesting they may be driven by distinct underlying mechanisms. PMID- 26381354 TI - Spectroscopic evidence of 3-hydroxyflavone sorption within MFI type zeolites: ESIPT and metal complexation. AB - Due to its chemical and photochemical properties and potential applications in numerous domains as a molecular probe, 3-hydroxyflavone (3HF) is a molecule of high interest. In particular, the processes of intramolecular proton transfer in the excited state and metallic complexation are known to be dependent on the chemical environment. In this context, the particular properties of zeolites make these microporous materials an environment adapted to study the reactivity of isolated molecules adsorbed in their porous void space. Thus, this report investigates the incorporation without any solvent of 3HF into the internal volume of various channel-type MFI zeolites. Using complementary techniques (diffuse reflectance UV-vis absorption, Raman scattering, FTIR, fluorescence emission and molecular modelling), very different spectral behaviours are observed in totally dealuminated silicalite-1 and in Al rich MZSM-5 (M = H(+), Na(+), Zn(2+)). In silicalite-1, the non-polar and non-protic internal micro environment does not induce any valuable interaction between 3HF and the channel walls. Therefore, the molecule shows easy tautomer formation upon excitation. Within HZSM-5, 3HF is adsorbed in close proximity of the acid proton of the zeolite which inhibits the intramolecular proton transfer and then, only the normal form is observed at the excited state. For NaZSM-5, the spectral data show an intermediary behaviour due to the aprotic but polar environment, in agreement with 3HF sorption in close proximity of the Na(+) extra framework cation. After mixing 3HF and ZnZSM-5, the spectral features clearly indicate metallic complexation of the guest molecule. The zeolite dependent reactivity reported here demonstrates the adsorption of the guest within the internal volume because the charge balancing cations which clearly control the reaction are principally located in the zeolite channels. The 3HF incorporation into the internal volume is proved by the decrease of the microporous volume observed by nitrogen adsorption-desorption isotherm measurements. The experimental data are confirmed by Monte Carlo molecular modelling which also predicts 3HF sorption in the zeolite channels in the proximity of charge compensating cations. Consequently, as the molecule dimensions are assumed to be slightly larger than the channel size, the flexibility of the molecule and the lattice deformation have to be considered to allow 3HF penetration into the zeolite void space. PMID- 26381353 TI - Imaging and energetics of single SSB-ssDNA molecules reveal intramolecular condensation and insight into RecOR function. AB - Escherichia coli single-stranded DNA (ssDNA) binding protein (SSB) is the defining bacterial member of ssDNA binding proteins essential for DNA maintenance. SSB binds ssDNA with a variable footprint of ~30-70 nucleotides, reflecting partial or full wrapping of ssDNA around a tetramer of SSB. We directly imaged single molecules of SSB-coated ssDNA using total internal reflection fluorescence (TIRF) microscopy and observed intramolecular condensation of nucleoprotein complexes exceeding expectations based on simple wrapping transitions. We further examined this unexpected property by single molecule force spectroscopy using magnetic tweezers. In conditions favoring complete wrapping, SSB engages in long-range reversible intramolecular interactions resulting in condensation of the SSB-ssDNA complex. RecO and RecOR, which interact with SSB, further condensed the complex. Our data support the idea that RecOR--and possibly other SSB-interacting proteins-function(s) in part to alter long-range, macroscopic interactions between or throughout nucleoprotein complexes by microscopically altering wrapping and bridging distant sites. PMID- 26381355 TI - Vibrating membrane with discontinuities for rapid and efficient microfluidic mixing. AB - This study presents a novel acoustic mixer comprising of a microfabricated silicon nitride membrane with a hole etched through it. We show that the introduction of the through hole leads to extremely fast and homogeneous mixing. When the membrane is immersed in fluid and subjected to acoustic excitation, a strong streaming field in the form of vortices is generated. The vortices are always observed to centre at the hole, pointing to the critical role it has on the streaming field. We hypothesise that the hole introduces a discontinuity to the boundary conditions of the membrane, leading to strong streaming vortices. With numerical simulations, we show that the hole's presence can increase the volume force responsible for driving the streaming field by 2 orders of magnitude, thus supporting our hypothesis. We investigate the mixing performance at different Peclet numbers by varying the flow rates for various devices containing circular, square and rectangular shaped holes of different dimensions. We demonstrate rapid mixing within 3 ms mixing time (90% mixing efficiency at 60 MUl min(-1) total flow rate, Peclet number equals 8333 +/- 3.5%) is possible with the current designs. Finally, we examine the membrane with two circular holes which are covered by air bubbles and compare it to when the membrane is fully immersed. We find that coupling between the holes' vortices occurs only when membrane is immersed; while with the bubble membrane, the upstream hole's vortices can act as a blockage to fluid flow passing it. PMID- 26381356 TI - The success of direct laryngoscopy in children with Klippel-Feil Syndrome. PMID- 26381357 TI - It is time for anesthetists to act as perioperative physicians. PMID- 26381358 TI - The Dynamics, energetics and selectivity of water chain-containing aquapores created by the self-assembly of aquafoldamer molecules. AB - Through a series of crystallographic snapshots of water chain-containing aquapores formed from numerous one-dimensionally aligned aquafoldamer molecules 2, we demonstrated here (1) a preferential recognition of the water molecules over methanol molecules by the assembled cavity-containing aquapores with a selectivity factor of at least 17.7, (2) the dynamic nature of the water chains and the aquapores in response to varying external stimuli that exert the most influential impact on the aromatic pi-pi stacking in the aquapores and (3) the aquapores undergo a significant rearrangement in order to accommodate water, rather than methanol, molecules. PMID- 26381359 TI - Three-Dimensional, Fibrous Lithium Iron Phosphate Structures Deposited by Magnetron Sputtering. AB - Crystalline, three-dimensional (3D) structured lithium iron phosphate (LiFePO4) thin films with additional carbon are fabricated by a radio frequency (RF) magnetron-sputtering process in a single step. The 3D structured thin films are obtained at deposition temperatures of 600 degrees C and deposition times longer than 60 min by using a conventional sputtering setup. In contrast to glancing angle deposition (GLAD) techniques, no tilting of the substrate is required. Thin films are characterized by X-ray diffraction (XRD), Raman spectrospcopy, scanning electron microscopy (SEM), cyclic voltammetry (CV), and galvanostatic charging and discharging. The structured LiFePO4+C thin films consist of fibers that grow perpendicular to the substrate surface. The fibers have diameters up to 500 nm and crystallize in the desired olivine structure. The 3D structured thin films have superior electrochemical properties compared with dense two-dimensional (2D) LiFePO4 thin films and are, hence, very promising for application in 3D microbatteries. PMID- 26381360 TI - Silver-Catalyzed Decarboxylative Azidation of Aliphatic Carboxylic Acids. AB - The catalytic decarboxylative nitrogenation of aliphatic carboxylic acids for the synthesis of alkyl azides is reported. A series of tertiary, secondary, and primary organoazides were prepared from easily available aliphatic carboxylic acids by using K2S2O8 as the oxidant and PhSO2N3 as the nitrogen source. The EPR experiment sufficiently proved that an alkyl radical process was generated in the process, and DFT calculations further supported the SET process followed by a stepwise SH2 reaction to afford azide product. PMID- 26381362 TI - Combustive, Postcombustive, and Tropospheric Butadiyne Oxidation by O2, Following Initial HO Attack. Theoretical Study. AB - Butadiyne (diacetylene, HC(4)H) is produced during combustions, and has been quantified in different flames as well as a biomass burning emission. Its reaction with the hydroxyl radical, HO((2)Pi(3/2)), under combustion conditions, was investigated in a thorough RRKM study by J. P. Senosiain, S. J. Klippenstein, and J. A.Miller (Proc. Combust. Inst. 2007, 31, 185-192). The present densityfunctional theory (DFT) study focuses on the mechanism of further oxidation by O(2)(3Sigma(g)(-)). The DFT(M06-2X)/cc-pVTZ reaction energy hypersurface for the system C(4)H(2)/HO*/O(2) is studied to define a variety of reaction pathways, and the relevant thermochemistry for temperatures ranging from 200 to 2500 K is assessed, thus encompassing combustive, postcombustive, and tropospheric conditions.Energies are then recomputed at the coupled cluster level[CCSD(T)/cc-pVTZ], and combined with the DFT thermochemistry.Finally, the role of the different reaction channels is assessed by RRKM-ME simulations in the same temperature range for P = 1 atm,to comprise the situation of emission in the troposphere and those pertaining to different flames. This shows that, when considering HO addition to the triple bond, dioxygen takes part in C(4)H(2) oxidation with higher efficiency at lower temperatures, whereas, as T rises, the O(2) adducts are inclined to redissociate: for instance, a 50% redissociation is estimated at T = 1800 K. For 200 < T < 1100 K, two polycarbonyl products (CHO.CO.C?CH and CHO.CO.CH?C?O) and two fragmentation products (HCOOH plus OC(*) C?CH) are the main species predicted as products from the addition channel (fragmentation is entropy-favored by higher T values). However, at higher temperatures, aninitial H abstraction by HO can give the but adiynyl radical (HC(4)(*)) as the starting point for subsequent dioxygen intervention.Then, new pathways opened by O(2) addition become accessible and bring about fragmentations mainly to HC(3)(*) + CO(2) and also to HC(3)(*)O + CO. PMID- 26381361 TI - De novo design and characterization of copper metallopeptides inspired by native cupredoxins. AB - Using de novo protein design, we incorporated a copper metal binding site within the three-helix bundle alpha3D (Walsh et al. Proc. Natl. Acad. Sci. U.S.A. 1999, 96, 5486-5491) to assess whether a cupredoxin center within an alpha-helical domain could mimic the spectroscopic, structural, and redox features of native type-1 copper (CuT1) proteins. We aimed to determine whether a CuT1 center could be realized in a markedly different scaffold rather than the native beta-barrel fold and whether the characteristic short Cu-S bond (2.1-2.2 A) and positive reduction potentials could be decoupled from the spectroscopic properties (epsilon600 nm = 5000 M(-1) cm(-1)) of such centers. We incorporated 2HisCys(Met) residues in three distinct alpha3D designs designated core (CR), chelate (CH), and chelate-core (ChC). XAS analysis revealed a coordination environment similar to reduced CuT1 proteins, producing Cu-S(Cys) bonds ranging from 2.16 to 2.23 A and Cu-N(His) bond distances of 1.92-1.99 A. However, Cu(II) binding to the CR and CH constructs resulted in tetragonal type-2 copper-like species, displaying an intense absorption band between 380 and 400 nm (>1500 M(-1) cm(-1)) and A|| values of (150-185) * 10(-4) cm(-4). The ChC construct, which possesses a metal binding site deeper in its helical bundle, yielded a CuT1-like brown copper species, with two absorption bands at 401 (4429 M(-1) cm(-1)) and 499 (2020 M(-1) cm(-1)) nm and an A|| value ~30 * 10(-4) cm(-4) greater than its native counterparts. Electrochemical studies demonstrated reduction potentials of +360 to +460 mV (vs NHE), which are within the observed range for azurin and plastocyanin. These observations showed that the designed metal binding sites lacked the necessary rigidity to enforce the appropriate structural constraints for a Cu(II) chromophore (EPR and UV-vis); however, the Cu(I) structural environment and the high positive potential of CuT1 centers were recapitulated within the alpha-helical bundle of alpha3D. PMID- 26381363 TI - Fluorescence Tracking of Genome Release during Mechanical Unpacking of Single Viruses. AB - Viruses package their genome in a robust protein coat to protect it during transmission between cells and organisms. In a reaction termed uncoating, the virus is progressively weakened during entry into cells. At the end of the uncoating process the genome separates, becomes transcriptionally active, and initiates the production of progeny. Here, we triggered the disruption of single human adenovirus capsids with atomic force microscopy and followed genome exposure by single-molecule fluorescence microscopy. This method allowed the comparison of immature (noninfectious) and mature (infectious) adenovirus particles. We observed two condensation states of the fluorescently labeled genome, a feature of the virus that may be related to infectivity. Beyond tracking the unpacking of virus genomes, this approach may find application in testing the cargo release of bioinspired delivery vehicles. PMID- 26381364 TI - Successful Treatment of Massive Pulmonary Embolism With Catheter-Directed Thrombolysis in a Patient With Lymphocele: A Rare Cause of Thromboembolism. AB - Pulmonary embolism is a frequent and mortal situation especially in high-risk patients. Although thrombolytics and anticoagulants are the main options in treatment, substantial portion of patients also have high bleeding risk. Therefore, new catheter-directed treatment strategies, such as ultrasound assisted transcatheter thrombolysis, gain importance in treatment options for intermediate and high-risk patients. Here, we report a case of massive pulmonary embolism due to the iatrogenic lymphocele after a radical retropubic prostatectomy procedure. The usage of ultrasound-assisted transcatheter thrombolysis was successful in such a high-risk patient. PMID- 26381365 TI - Treatment for Inappropriate Sinus Tachycardia. AB - Inappropriate Sinus Tachycardia (IST) is a chronic medical condition with a wide variety of clinical presentations making it, sometimes, very insidious at the time of the diagnosis. Several therapeutic options, including, pharmacotherapy, cardiac rehabilitation, and modification or ablation of the sinus node, have been proposed for the management of IST, but because of the complexity and lack of understanding of pathophysiology, it can be difficult to manage, despite the numerous treatment options currently available. The purpose of this review is to analyze the treatment for IST, focusing on the role of newer therapy and the potential benefits in the management of this cardiac rhythm disturbance. PMID- 26381366 TI - Athletic Directors' Barriers to Hiring Athletic Trainers in High Schools. AB - CONTEXT: In its best-practices recommendation, the Inter-Association Task Force for Preventing Sudden Death in Secondary School Athletics Programs urged all high schools to have a certified athletic trainer (AT) on staff. Despite the recommendation, many high schools lack the medical services of an AT. OBJECTIVE: To examine the barriers that athletic directors (ADs) face in hiring ATs in public high schools and in providing medical coverage for their student-athletes. DESIGN: Qualitative study. SETTING: Semistructured telephone interviews. PATIENTS OR OTHER PARTICIPANTS: Twenty full-time public high school ADs (17 men, 3 women) from various geographical regions of the United States (6 North, 4 South, 4 Midwest, 6 West) participated. Data saturation guided the total number of participants. DATA COLLECTION AND ANALYSIS: We completed telephone interviews guided by a semistructured questionnaire with all participants. Interviews were recorded and transcribed verbatim. Multiple-analyst triangulation and peer review were included as steps to establish data credibility. We analyzed the data using the principles of the general inductive approach. RESULTS: We identified 3 themes. Lack of power represented the inability of an AD to hire an AT, which was perceived to be a responsibility of the superintendent and school board. Budget concerns pertained to the funding allocated to specific resources within a school, which often did not include an AT. Nonbudget concerns represented rural locations without clinics or hospitals nearby; misconceptions about the role of an AT, which led to the belief that first-aid-trained coaches are appropriate medical providers; and community support from local clinics, hospitals, and volunteers. CONCLUSIONS: Many ADs would prefer to employ ATs in their schools; however, they perceive that they are bound by the hiring and budgeting decisions of superintendents and school boards. Public school systems are experiencing the consequences of national budget cuts and often do not have the freedom to hire ATs when other school staff are being laid off. PMID- 26381367 TI - Preventing Sudden Cardiac Death: Automated External Defibrillators in Ohio High Schools. AB - CONTEXT: Ohio passed legislation in 2004 for optional public funding of automated external defibrillators (AEDs) in all Ohio high schools. OBJECTIVE: To report occurrences of sudden cardiac arrest in which AEDs were used in Ohio high schools and to evaluate the adherence of Ohio high schools with AEDs to state law and published guidelines on AEDs and emergency action plans (EAPs) in schools. DESIGN: Cross-sectional survey. SETTING: Web-based survey. PATIENTS OR OTHER PARTICIPANTS: A total of 264 of 827 schools that were members of the Ohio High School Athletic Association. MAIN OUTCOME MEASURE(S): We surveyed schools on AED use, AED maintenance, and EAPs. RESULTS: Twenty-five episodes of AED deployment at 22 schools over an 11-year period were reported; 8 (32%) involved students and 17 (68%) involved adults. The reported survival rate was 60% (n = 15). Most events (n = 20, 80%) in both students and adults occurred at or near athletic facilities. The annual use rate of AEDs was 0.7%. Fifty-three percent (n = 140) of schools reported having an EAP in place for episodes of cardiac arrest. Of the schools with EAPs, 57% (n = 80) reported having rehearsed them. CONCLUSIONS: Our data supported the placement of AEDs in high schools given the frequency of use for sudden cardiac arrest and the survival rate reported. They also suggested the need for increased awareness of recommendations for EAPs and the need to formulate and practice EAPs. School EAPs should emphasize planning for events in the vicinity of athletic facilities. PMID- 26381368 TI - Pain-Coping Traits of Nontraditional Women Athletes: Relevance to Optimal Treatment and Rehabilitation. AB - CONTEXT: The primary goal of traditional treatment and rehabilitation programs is to safely return athletes to full functional capacity. Nontraditional activities such as rock climbing or rodeo are typically less training structured and coach structured; individualism, self-determination, and autonomy are more prevalent than observed in athletes in National Collegiate Athletic Association (NCAA) sponsored sports. The limited research available on nontraditional athletes has provided the athletic trainer little insight into the coping skills and adaptations to stressors that these athletes may bring into the clinical setting, especially among the growing number of women participating in these types of activities. A better understanding of the pain-coping traits of nontraditional competitors would enhance insight and triage procedures while heading off potential athlete-related risk factors in the clinical setting. OBJECTIVE: To quantify and compare pain-coping traits among individual-sport women athletes participating in nontraditional versus traditional NCAA-structured competition, with relevance to optimal treatment and rehabilitation. DESIGN: Cross-sectional study. SETTING: Data collected during each participant's respective group meeting before seasonal activity. Participants or Other Participants : A total of 298 athletes involved in either nontraditional, non-NCAA individual sports (n = 152; mean age = 20.2 +/- 1.3 years; downhill skiing, martial arts, rock climbing, rodeo, skydiving, telemark skiing) or traditional NCAA sports (n = 146; mean age = 20.3 +/- 1.4 years; equestrian, golf, swimming/diving, tennis, track). MAIN OUTCOME MEASURE(S): All participants completed the Sports Inventory for Pain, a sport-specific, self-report instrument that measures pain-coping traits relevant to competition, treatment, and rehabilitation. Trait measures were direct coping, cognitive, catastrophizing, avoidance, body awareness, and total coping response. Data were grouped for analyses by type of athlete (nontraditional, traditional). RESULTS: We found a significant main effect for type of athlete (Wilks' lambda F6,291 = 12.922; P = .0001). Nontraditional sport athletes scored lower on direct coping (P = .0001), cognitive (P = .0001), catastrophizing (P = .0001), and total coping response (P = .0001) than traditional athletes. CONCLUSIONS: Women participating in nontraditional individual-sport activity revealed less pronounced pain-coping traits than women participating in more coach-structured, traditional NCAA sports. Sport and medical personnel should consider the type of athlete when prescribing training, treatment, and rehabilitation for optimal performance and return to play. PMID- 26381370 TI - Factors associated with geographic tongue and fissured tongue. AB - OBJECTIVES: The primary objective of this study was to investigate the association of systemic diseases, use of medications, allergies and tobacco habits with geographic tongue (GT) and fissured tongue (FT) lesions. The secondary objectives were to evaluate the clinical characteristics of tongue lesions and to compare the overall results for referred and non-referred patients. METHODOLOGY: Non-referred patients with GT (GTgp; n = 130) and FT (FTgp; n = 62) were examined by general practitioners (gp) and compared to a control group without oral mucosal lesions (C; n = 1029). Referred patients with GT (GTs; n = 166) and FT (FTs; n = 15) were examined by oral medicine specialists (s) and compared to GTgp and FTgp. Statistical analyses were performed using unpaired t-test or Fisher's exact test. A multiple logistic regression model was developed to control for age and gender as confounders. RESULTS: Compared to the C group, GTgp patients used more anti-hypertensive medications and Swedish snus (p < 0.01). The GTgp group consisted of older males (p < 0.001) compared to C. Compared to the GTgp group, the GTs group was younger, more likely to have symptomatic lesions (p < 0.0001) and comprised of more females. Among the groups examined, FT patients had the highest mean age. CONCLUSION: This study identified an association between GT and anti-hypertensive medications, as well as the use of Swedish snus. It also found differences in the activities and symptoms of the lesions between referred patients and their counterparts who were seen in general dental practice; these parameters influenced the results when these conditions were taken into account. PMID- 26381369 TI - Masked Repetition Priming in Treatment of Anomia: A Phase 2 Study. AB - PURPOSE: Previous research has demonstrated that exposure to masked primes may improve naming accuracy for individuals with anomia. This study investigates the effect of repeated exposures to masked identity primes paired with pictures over multiple trials, sessions, and days on the ability of people with anomia to name those pictures. METHOD: Four participants with anomia completed this single subject, multiple-baseline design study. Twelve treatment sessions were conducted for each of 2 semantic categories. Comparisons of performance on naming probes were made between items that were primed, unprimed but seen the same number of times, and unprimed and seen only during naming probes. RESULTS: All participants showed some gains in naming trained items although to varying degrees, and trained (primed) items generally showed greater improvement than untrained items seen the same number of times. Cross-category generalization was observed for some participants, but little to no within-category generalization occurred. Minimal changes occurred on measures of general language ability. CONCLUSIONS: These data provide continued evidence that masked repetition priming can have a positive effect on naming for people with anomia. Factors that may influence participant response and additional questions that must be settled for this line of research to continue are discussed. PMID- 26381371 TI - Does performing cesarean section after onset of labor has positive effect on neonatal respiratory disorders? AB - OBJECTIVE: The aim of this study is to evaluate whether neonatal respiratory disorders relate to the onset of labor or labor pain in patients with history of previous cesarean section. METHODS: This prospective controlled study comprised 164 patients, grouped according to the presence of labor and related labor pain. All patients in both groups were applied cesarean section at 38 weeks gestational age or beyond due to previous cesarean section. The cord blood pH, Apgar scores and the need for the neonatal intensive care unit were compared. RESULTS: There was a greater need for the neonatal intensive care unit in the control group and the cord blood pH values were higher in the study group (p < 0.05). No significant difference was determined between the groups in respect of Apgar scores (p > 0.05). CONCLUSION: The onset of labor and related labor pain provide a positive contribution to a reduction in neonatal respiratory disorders. Therefore, it can be considered reasonable to perform a cesarean section after the onset of labor or related pain. PMID- 26381372 TI - The Role of Practical Advice in Bioterrorism News Coverage. AB - This study examined the role of crisis advice appearing in US news coverage of the 2001 anthrax attacks. Coverage of any crisis can spark public outrage, including fear, speculation, and contradictory or confusing evidence, especially when the stories do not contain practical advice. Five coders analyzed 833 news stories from 272 major US newspapers, the Associated Press, National Public Radio, and 4 major US television networks. Practical advice appeared in only a quarter of the stories, even though practical advice for self-protection was mentioned 3 times more often than the vague advice that simply advised people not to panic. Public health officials provided the most practical advice, while scientists provided the least practical advice. Stories containing practical advice also provided more elucidating information, explaining why the threat was low, reducible, treatable, and detectable. Over the 3 phases of the anthrax crisis, an inverse relationship appeared between the amount of news coverage containing practical advice compared to "outrage rhetoric." Stories mentioned practical advice more often during the post-impact phase than earlier in the crisis. Elucidating, explanatory advice emphasized actions, risk comparisons, and tradeoffs. The findings indicate that when journalists use credible sources to provide practical advice and avoid speculation, their coverage can prevent the spread of misinformation and confusion during a bioterror attack. Also, journalists should provide context and sourcing when discussing advice during the outbreak and impact phases of the crisis, because these explanations could counteract outrage and threat distortion. PMID- 26381373 TI - A No-Notice Drill of Hospital Preparedness in Responding to Ebola Virus Disease in Taiwan. AB - The Ebola virus was first discovered in 1976, but the outbreak of Ebola virus disease that began in Guinea, West Africa, in December 2013 shocked the world. It is the largest and most severe epidemic of Ebola virus disease to date. The US Centers for Disease Control and Prevention confirmed that inadequate implementation of the policy of acquiring travel history led to a delay in identifying the first imported Ebola virus disease case. The Taiwan Centers for Disease Control developed a no-notice drill that used a simulated patient to assess hospitals' emergency preparedness capacity in responding to Ebola virus disease. Despite the fact that regular inspection shows that more than 90% of regional hospitals and medical centers inquired about patients' travel history, occupation, contact history, and cluster information, the no-notice drill revealed that more than 40% of regional hospitals and medical centers failed to ask emergency room patients about these factors. Therefore, to assist in inquiries about travel history, occupation, contact history, and cluster information in emergency triage and outpatient settings, the Taiwan CDC revised the criteria for hospital infection control inspection. It requested that hospitals issue appropriate reminders and implement process control mechanisms to block diagnostic processes in instances in which healthcare workers do not inquire about travel history, occupation, contact history, and cluster information. Furthermore, the Taiwan CDC will continue no-notice inspections in order to strengthen hospitals' infection control measures and reduce the risk of infectious disease transmission in the healthcare system. PMID- 26381374 TI - Silicon: a duo synergy for regulating crop growth and hormonal signaling under abiotic stress conditions. AB - Abiotic stresses, such as salinity, heavy metals and drought, are some of the most devastating factors hindering sustainable crop production today. Plants use their own defensive strategies to cope with the adverse effects of these stresses, via the regulation of the expression of essential phytohormones, such as gibberellins (GA), salicylic acid (SA), jasmonates (JA), abscisic acid (ABA) and ethylene (ET). However, the efficacy of the endogenous defensive arsenals of plants often falls short if the stress persists over an extended period. Various strategies are developed to improve stress tolerance in plants. For example, silicon (Si) is widely considered to possess significant potential as a substance which ameliorate the negative effects of abiotic stresses, and improves plant growth and biomass accumulation. This review aims to explain how Si application influences the signaling of the endogenous hormones GA, SA, ABA, JA and ET during salinity, wounding, drought and metal stresses in crop plants. Phytohormonal cross talk plays an important role in the regulation of induced defences against stress. However, detailed molecular and proteomic research into these interactions is needed in order to identify the underlying mechanisms of stress tolerance that is imparted by Si application and uptake. PMID- 26381375 TI - Artemether-lumefantrine treatment of uncomplicated Plasmodium falciparum malaria: a systematic review and meta-analysis of day 7 lumefantrine concentrations and therapeutic response using individual patient data. AB - BACKGROUND: Achieving adequate antimalarial drug exposure is essential for curing malaria. Day 7 blood or plasma lumefantrine concentrations provide a simple measure of drug exposure that correlates well with artemether-lumefantrine efficacy. However, the 'therapeutic' day 7 lumefantrine concentration threshold needs to be defined better, particularly for important patient and parasite sub populations. METHODS: The WorldWide Antimalarial Resistance Network (WWARN) conducted a large pooled analysis of individual pharmacokinetic-pharmacodynamic data from patients treated with artemether-lumefantrine for uncomplicated Plasmodium falciparum malaria, to define therapeutic day 7 lumefantrine concentrations and identify patient factors that substantially alter these concentrations. A systematic review of PubMed, Embase, Google Scholar, ClinicalTrials.gov and conference proceedings identified all relevant studies. Risk of bias in individual studies was evaluated based on study design, methodology and missing data. RESULTS: Of 31 studies identified through a systematic review, 26 studies were shared with WWARN and 21 studies with 2,787 patients were included. Recrudescence was associated with low day 7 lumefantrine concentrations (HR 1.59 (95% CI 1.36 to 1.85) per halving of day 7 concentrations) and high baseline parasitemia (HR 1.87 (95% CI 1.22 to 2.87) per 10-fold increase). Adjusted for mg/kg dose, day 7 concentrations were lowest in very young children (<3 years), among whom underweight-for-age children had 23% (95% CI -1 to 41%) lower concentrations than adequately nourished children of the same age and 53% (95% CI 37 to 65%) lower concentrations than adults. Day 7 lumefantrine concentrations were 44% (95% CI 38 to 49%) lower following unsupervised treatment. The highest risk of recrudescence was observed in areas of emerging artemisinin resistance and very low transmission intensity. For all other populations studied, day 7 concentrations >=200 ng/ml were associated with >98% cure rates (if parasitemia <135,000/MUL). CONCLUSIONS: Current artemether lumefantrine dosing recommendations achieve day 7 lumefantrine concentrations >=200 ng/ml and high cure rates in most uncomplicated malaria patients. Three groups are at increased risk of treatment failure: very young children (particularly those underweight-for-age); patients with high parasitemias; and patients in very low transmission intensity areas with emerging parasite resistance. In these groups, adherence and treatment response should be monitored closely. Higher, more frequent, or prolonged dosage regimens should now be evaluated in very young children, particularly if malnourished, and in patients with hyperparasitemia. PMID- 26381376 TI - Identification of cultural determinants of antibiotic use cited in primary care in Europe: a mixed research synthesis study of integrated design "Culture is all around us". AB - BACKGROUND: Inappropriate antibiotic prescribing, particularly for respiratory tract infections (RTI) in ambulatory care, has become a worldwide public health threat due to resulting antibiotic resistance. In spite of various interventions and campaigns, wide variations in antibiotic use persist between European countries. Cultural determinants are often referred to as a potential cause, but are rarely defined. To our knowledge, so far no systematic literature review has focused on cultural determinants of antibiotic use. The aim of this study was to identify cultural determinants, on a country-specific level in ambulatory care in Europe, and to describe the influence of culture on antibiotic use, using a framework of cultural dimensions. METHOD: A computer-based systematic literature review was conducted by two research teams, in France and in Norway. Eligible publications included studies exploring antibiotic use in primary care in at least two European countries based on primary study results, featuring a description of cultural determinants, and published between 1997 and 2015. Quality assessment was conducted independently by two researchers, one in each team, using appropriate checklists according to study design. Each included paper was characterized according to method, countries involved, sampling and main results, and cultural determinants mentioned in each selected paper were extracted, described and categorized. Finally, the influence of Hofstede's cultural dimensions associated with antibiotic consumption within a primary care setting was described. RESULTS: Among 24 eligible papers, 11 were rejected according to exclusion criteria. Overall, 13 papers meeting the quality assessment criteria were included, of which 11 used quantitative methods and two qualitative or mixed methods. The study participants were patients (nine studies) and general practitioners (two studies). This literature review identified various cultural determinants either patient-related (illness perception/behaviour, health-seeking behaviour, previous experience, antibiotic awareness, drug perception, diagnosis labelling, work ethos, perception of practitioner) or practitioner-related (RTI management, initial training, antibiotic awareness, legal issues, practice context) or both (antibiotic awareness). DISCUSSION AND CONCLUSION: Cultural factors should be considered as exerting an ubiquitous influence on all the consecutive stages of the disease process and seem closely linked to education. Interactions between determinant categories, cultural dimensions and antibiotic use in primary care are multiple, complex and require further investigation within overlapping disciplines. The context of European projects seems particularly relevant. PMID- 26381377 TI - Tools and best practices for data processing in allelic expression analysis. AB - Allelic expression analysis has become important for integrating genome and transcriptome data to characterize various biological phenomena such as cis regulatory variation and nonsense-mediated decay. We analyze the properties of allelic expression read count data and technical sources of error, such as low quality or double-counted RNA-seq reads, genotyping errors, allelic mapping bias, and technical covariates due to sample preparation and sequencing, and variation in total read depth. We provide guidelines for correcting such errors, show that our quality control measures improve the detection of relevant allelic expression, and introduce tools for the high-throughput production of allelic expression data from RNA-sequencing data. PMID- 26381378 TI - Preoperative palsy score has no significant association with survival in non small-cell lung cancer patients with spinal metastases who undergo spinal surgery. AB - BACKGROUND: Survival is a key factor physicians consider when selecting a treatment modality for the treatment of spinal metastases. Various assessment systems can predict length of survival and facilitate selection of the most appropriate treatment. Spinal palsy is a prognostic parameter in the Tokuhashi scoring system but not in the Tomita scoring system. A limitation of these scoring systems is that studies of them have included different tumor types. The aim of this study was to evaluate the usefulness of preoperative neurological status as a prognostic factor in non-small-cell lung cancer patients with spinal metastases who underwent surgical treatment. METHODS: From November 2000 to March 2010, 50 patients with symptomatic metastatic spinal cord compression secondary to non-small-cell lung cancer underwent palliative surgery. Data collected included patient age and sex, tumor histology, date of surgery, death or last follow-up, preoperative and postoperative ambulatory status according to the Frankel grading system, body mass index (BMI), number of vertebra involved, number of other bone metastasis, visceral metastasis, and preoperative Karnofsky performance status. Log-rank test and multivariate Cox proportional hazard regressions were used to evaluate possible prognostic factors. RESULTS: The mean patient age was 61.6 years (range, 20-87 years), and 34 were male and 16 were female. The median postoperative survival time was 7.5 months. The median survival was 2.5 months (95% confidence interval (CI): 1.22-16.3 months) in the Frankel A + B group and 8.0 months (95% CI: 5.52-9.89 months) in the Frankel C + D group (p = 0.87). Multivariate Cox proportional hazard regressions showed that preoperative performance status was significantly associated with survival. Preoperative palsy score had no statistically significant association with survival. CONCLUSIONS: Preoperative palsy score had no statistically significant association with survival in non-small-cell lung cancer patients with spinal metastases who underwent spinal surgery in this study. PMID- 26381379 TI - epsilon-Polylysine and next-generation dendrigraft poly-L-lysine: chemistry, activity, and applications in biopharmaceuticals. AB - Polylysine is an important class of polyamino acids with a broad spectrum of applications in biomedical research and development. It can be divided into two classes, alpha-polylysine and epsilon-polylysine, the former is synthesized by artificial chemical synthesis and has limited applications due to its high toxicity, and the latter is produced by microbial synthesis as a class of natural polymers and is widely used in various food, medicinal, and electronics products. Another major class of synthetic polymers is dendrimers (after linear, cross linked, and branched polymers). Dendrigraft poly-L-lysine (DGL) has the favorable properties of polylysine and dendrimers, with a broad spectrum of applications in drug discovery and development, including drug delivery, gene carriers, diagnostic imaging, diagnostics, biosensors, and special cancer therapies (such as boron neutron capture therapy and photodynamic therapy). As there are still some problems with the development of DGL, further research is warranted for its broad applications. PMID- 26381380 TI - Evidence for the Intercalation of Lipid Acyl Chains into Polypropylene Fiber Matrices. AB - Headgroup-functionalized lipids are being developed as ligand tethers for high selectivity separations on polypropylene capillary-channeled polymer fiber stationary phases. Surface modification is affected under ambient conditions from aqueous solution. This basic methodology has promise in many areas where robust modifications are desired on hydrophobic surfaces. In order to understand the mode of adsorption of the lipid tail to the polypropylene surface, lipids labeled with the environmentally sensitive 7-nitro-2-1,3-benzoxadiazol-4-yl (NBD) fluorophore were used, with NBD covalently attached to the headgroup (NBD-PE) or the acyl chain (acyl NBD-PE) of the lipid. When modified with the acyl NBD-PE, fluorescence imaging of the fiber at excitation wavelengths increasing from 470 to 510 nm caused a 32 nm shift in emission toward the red edge of the absorption band, indicating that the NBD molecule (and thus the lipid tail) is motionally restricted. Fluorescence imaging on fibers modified with NBD-PE or the free NBD Cl dye molecule yields no change in the emission response. The results of these imaging studies provide evidence that the acyl chain portions of the lipids intercalate into free volume of the polypropylene fiber structure, yielding a robust means of surface modification and the potential for high ligand densities. PMID- 26381382 TI - The relationship between appetite and food preferences in British and Australian children. AB - BACKGROUND: Appetitive traits and food preferences are key determinants of children's eating patterns but it is unclear how these behaviours relate to one another. This study explores relationships between appetitive traits and preferences for fruits and vegetables, and energy dense, nutrient poor (noncore) foods in two distinct samples of Australian and British preschool children. METHODS: This study reports secondary analyses of data from families participating in the British GEMINI cohort study (n = 1044) and the control arm of the Australian NOURISH RCT (n = 167). Food preferences were assessed by parent completed questionnaire when children were aged 3-4 years and grouped into three categories; vegetables, fruits and noncore foods. Appetitive traits; enjoyment of food, food responsiveness, satiety responsiveness, slowness in eating, and food fussiness were measured using the Children's Eating Behaviour Questionnaire when children were 16 months (GEMINI) or 3-4 years (NOURISH). Relationships between appetitive traits and food preferences were explored using adjusted linear regression analyses that controlled for demographic and anthropometric covariates. RESULTS: Vegetable liking was positively associated with enjoyment of food (GEMINI; beta = 0.20 +/- 0.03, p < 0.001, NOURISH; beta = 0.43 +/- 0.07, p < 0.001) and negatively related to satiety responsiveness (GEMINI; beta = -0.19 +/- 0.03, p < 0.001, NOURISH; beta = -0.34 +/- 0.08, p < 0.001), slowness in eating (GEMINI; beta = -0.10 +/- 0.03, p = 0.002, NOURISH; beta = -0.30 +/- 0.08, p < 0.001) and food fussiness (GEMINI; beta = -0.30 +/- 0.03, p < 0.001, NOURISH; beta = -0.60 +/- 0.06, p < 0.001). Fruit liking was positively associated with enjoyment of food (GEMINI; beta = 0.18 +/- 0.03, p < 0.001, NOURISH; beta = 0.36 +/- 0.08, p < 0.001), and negatively associated with satiety responsiveness (GEMINI; beta = -0.13 +/- 0.03, p < 0.001, NOURISH; beta = -0.24 +/- 0.08, p = 0.003), food fussiness (GEMINI; beta = -0.26 +/- 0.03, p < 0.001, NOURISH; beta = -0.51 +/- 0.07, p < 0.001) and slowness in eating (GEMINI only; beta = -0.09 +/- 0.03, p = 0.005). Food responsiveness was unrelated to liking for fruits or vegetables in either sample but was positively associated with noncore food preference (GEMINI; beta = 0.10 +/- 0.03, p = 0.001, NOURISH; beta = 0.21 +/- 0.08, p = 0.010). CONCLUSION: Appetitive traits linked with lower obesity risk were related to lower liking for fruits and vegetables, while food responsiveness, a trait linked with greater risk of overweight, was uniquely associated with higher liking for noncore foods. PMID- 26381381 TI - Mechanistic principles of antisense targets for the treatment of spinal muscular atrophy. AB - Spinal muscular atrophy (SMA) is a major neurodegenerative disorder of children and infants. SMA is primarily caused by low levels of SMN protein owing to deletions or mutations of the SMN1 gene. SMN2, a nearly identical copy of SMN1, fails to compensate for the loss of the production of the functional SMN protein due to predominant skipping of exon 7. Several compounds, including antisense oligonucleotides (ASOs) that elevate SMN protein from SMN2 hold the promise for treatment. An ASO-based drug currently under Phase III clinical trial employs intronic splicing silencer N1 (ISS-N1) as its target. Cumulative studies on ISS N1 reveal a wealth of information with significance to the overall therapeutic development for SMA. Here, the authors summarize the mechanistic principles behind various antisense targets currently available for SMA therapy. PMID- 26381384 TI - 2014 Balint Orban Memorial Program Abstracts - Clinical Science. PMID- 26381383 TI - What research agenda could be generated from the European General Practice Research Network concept of Multimorbidity in Family Practice? AB - BACKGROUND: Multimorbidity is an intuitively appealing, yet challenging, concept for Family Medicine (FM). An EGPRN working group has published a comprehensive definition of the concept based on a systematic review of the literature which is closely linked to patient complexity and to the biopsychosocial model. This concept was identified by European Family Physicians (FPs) throughout Europe using 13 qualitative surveys. To further our understanding of the issues around multimorbidity, we needed to do innovative research to clarify this concept. The research question for this survey was: what research agenda could be generated for Family Medicine from the EGPRN concept of Multimorbidity? METHODS: Nominal group design with a purposive panel of experts in the field of multimorbidity. The nominal group worked through four phases: ideas generation phase, ideas recording phase, evaluation and analysis phase and a prioritization phase. RESULTS: Fifteen international experts participated. A research agenda was established, featuring 6 topics and 11 themes with their corresponding study designs. The highest priorities were given to the following topics: measuring multimorbidity and the impact of multimorbidity. In addition the experts stressed that the concept should be simplified. This would be best achieved by working in reverse: starting with the outcomes and working back to find the useful variables within the concept. CONCLUSION: The highest priority for future research on multimorbidity should be given to measuring multimorbidity and to simplifying the EGPRN model, using a pragmatic approach to determine the useful variables within the concept from its outcomes. PMID- 26381385 TI - Reminiscences of the Late Professor Per-Ingvar Branemark. PMID- 26381386 TI - Leptin/adiponectin ratio predicts poststroke neurological outcome. AB - BACKGROUND AND AIMS: Different adipokines have been associated with atherosclerotic plaque rupture and cardiovascular events, such as acute ischaemic stroke (AIS). However, the potential role of these molecules in postischaemic brain injury remains largely unknown. METHODS AND METHODS: We performed a substudy analysis on nonobese patients with first atherothrombotic stroke (n = 35) from a recently published prospective cohort. Primary endpoint was to investigate the predictive value of serum leptin/adiponectin ratio on neurological recovery at 90 days after AIS. The secondary endpoint was the predictive value of serum adipokine levels of clinical and radiological outcomes at a shorter follow-up (at days 1 and 7 after AIS). The radiological evaluation included ischaemic lesion volume and haemorrhagic transformation (HT). The clinical examination was based on National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS). RESULTS: At day 1 after AIS, serum leptin and leptin/adiponectin ratio were increased and inversely correlated with both radiological and clinical parameters at all follow-up time points. Once identified the best cut-off points by receiver operating characteristic (ROC) analysis, risk analysis showed that higher circulating leptin improved neurological recovery at day 90. In addition, leptin/adiponectin ratio maintained statistical significance after adjustment for age, gender and thrombolysis, also predicting the occurrence of HT in the first 7 days after AIS (adjusted OR 0.15 [95% CI 0.03-0.83); P = 0.030]). CONCLUSIONS: Higher leptin/adiponectin ratio at day 1 predicted better neurological outcomes in patients with atherothrombotic AIS and might be potentially useful as a prognostic biomarker of the disease. PMID- 26381387 TI - Host-feeding behaviour of Dermacentor reticulatus and Dermacentor marginatus in mono-specific and inter-specific infestations. AB - BACKGROUND: Given the sympatric occurrence in some regions of Europe and the great epidemiological significance of D. reticulatus and D. marginatus species, we investigated the behaviour of these ticks during inter-specific and mono specific host infestations. FINDINGS: The investigations were conducted on rabbits at 20 +/- 3 degrees C and humidity of 38 +/- 1 %. The inter-specific infestations groups consisted of 20 females and ten males of D. marginatus and 20 females and ten males of D. reticulatus on each host, whereas mono-specific infestations involved 40 females and 20 males of each species. The investigations have demonstrated competition between the two tick species resulting in modification of the behaviour on the host and the feeding course in D. marginatus females by the presence of D. reticulatus. In the inter-specific group, D. marginatus females attached for a longer time (mean 2.74 +/- 1.12 h) than in the mono-specific group (mean 1.24 +/- 0.97 h) (p < 0.0001). The feeding period of these females was shorter (9.45 +/- 1.30 days) than in the mono-specific group (13.15 +/- 2.53 days) (p < 0.0001), but they exhibited a statistically significantly higher body weight in comparison with the females from the mono specific infestation (p = 0.0155). In D. reticulatus females, no significant difference was found in the host attachment and feeding rates between the mono specific and inter-specific groups. CONCLUSIONS: The differences in the behaviour of the females from both species during co-feeding reflect physiological adaptation to environmental conditions, which enables them to ingest blood and reproduce. During co-feeding of D. reticulatus and D. marginatus on the same host, two inter-specific systems with different physiological features are formed, which may influence the transmission of tick-borne pathogens. PMID- 26381388 TI - The Role of School Social Environment on Dental Caries Experience in 8- to 12 Year-Old Brazilian Children: A Multilevel Analysis. AB - AIM: Although children spend most of their time involved in activities related to school, few studies have focused on the association between school social environment and oral health. This cross-sectional study assessed individual and school-related social environment correlates of dental caries in Brazilian schoolchildren aged 8-12 years. METHODS: A sample of children from 20 private and public schools (n=1,211) was selected. Socio-economic data were collected from parents, and data regarding children characteristics were collected from children using a questionnaire. Dental examinations were performed to assess the presence of dental plaque: dental caries experience (DMFT>=1) and dental caries severity (mean dmf-t/DMF-T). The social school environment was assessed by a questionnaire administered to school coordinators. Multilevel Poisson regression was used to investigate the association between school social environment and dental caries prevalence and experience. RESULTS: The dental caries prevalence was 32.4% (95% confidence interval: 29.7-35.2) and the mean dmf-t/DMF-T was 1.84 (standard deviation: 2.2). Multilevel models showed that the mean dmf-t/DMF-T and DMFT>=1 were associated with lower maternal schooling and higher levels of dental plaque. For contextual variables, schools offering after-hours sports activities were associated with a lower prevalence of dental caries and a lower mean of dmf-t/DMF T, while the occurrence of violence and theft episodes was positively associated with dental caries. CONCLUSIONS: The school social environment has an influence on dental caries in children. The results suggest that strategies focused on the promotion of healthier environments should be stimulated to reduce inequalities in dental caries. PMID- 26381390 TI - Polydimethylsiloxane SlipChip for mammalian cell culture applications. AB - This paper reports a polydimethylsiloxane (PDMS) SlipChip for in vitro cell culture applications, multiple-treatment assays, cell co-cultures, and cytokine detection assays. The PDMS SlipChip is composed of two PDMS layers with microfluidic channels on each surface that are separated by a thin silicone fluid (Si-fluid) layer. The integration of Si-fluid enables the two PDMS layers to be slid to different positions; therefore, the channel patterns can be re-arranged for various applications. The SlipChip design significantly reduces the complexity of sample handling, transportation, and treatment processes. To apply the developed SlipChip for cell culture applications, human lung adenocarcinoma epithelial cells (A549) and lung fibroblasts (MRC-5) were cultured to examine the biocompatibility of the developed PDMS SlipChip. Moreover, embryonic pluripotent stem cells (ES-D3) were also cultured in the device to evaluate the retention of their stemness in the device. The experimental results show that cell morphology, viability and proliferation are not affected when the cells are cultured in the SlipChip, indicating that the device is highly compatible with mammalian cell culture. In addition, the stemness of the ES-D3 cells was highly retained after they were cultured in the device, suggesting the feasibility of using the SlipChip for stem cell research. Various cell experiments, such as simultaneous triple staining of cells and co-culture of MRC-5 with A549 cells, were also performed to demonstrate the functionalities of the PDMS SlipChip. Furthermore, we used a cytokine detection assay to evaluate the effect of endotoxin (lipopolysaccharides, LPS) treatment on the cytokine secretion of A549 cells using the SlipChip. The developed PDMS SlipChip provides a straightforward and effective platform for various on-chip in vitro cell cultures and consequent analysis, which is promising for a number of cell biology studies and biomedical applications. PMID- 26381389 TI - Insights into the mechanism of idiopathic left ventricular tachycardia: a case report and literature review. AB - Left ventricular posterior fascicular tachycardia (LVPFT) is an idiopathic form of VT characterized by right bundle branch block morphology and left axis deviation. The mechanism of LPFVT is thought to be localized reentry close to the posterior fascicle. We present the case of a 24-year-old medical student who was admitted to the emergency department complaining of palpitations. The ECG showed an aspect suggestive of LVPFT. Vagal maneuvers, adenosine and i.v. Metoprolol were ineffective in terminating the arrhythmia. Conversion to sinus rhythm was obtained 10 h later, with i.v Amiodarone. The ECG in sinus rhythm showed left posterior fascicular block. Because antiarrhythmic drugs were not desired by the patient, VT ablation was proposed. The electrophysiological study identified the mechanism of arrhythmia to be reentry using the slowly conducting verapamil sensitive fibers as the antegrade limb and the posterior fascicle as the retrograde limb. Radiofrequency applications near the posterior fascicle, in the lower half of the interventricular septum, at the junction of the two proximal thirds with the distal third interrupted the tachycardia and made it non inducible at programmed stimulation. The case is unusual as the patient had a left posterior fascicular block during sinus rhythm before ablation. This demonstrates that the reentry circuit of VT does not need antegrade conduction through the posterior fascicle for perpetuation. PMID- 26381391 TI - How to Supplement Iron in Patients with Renal Anemia. AB - Iron deficiency is a major cause of hyporesponsiveness to erythropoiesis stimulating agents (ESAs) and is often observed in chronic kidney disease (CKD) patients with anemia. With iron supplementation, ESA doses can be decreased, resulting in lower treatment costs and possibly lower cardiovascular risks that are associated with high-dose ESA therapy. The 2012 Kidney Disease: Improving Global Outcomes Guideline specified ferritin <= 500 ng/ml and transferrin saturation (TSAT) <= 30% as thresholds of iron parameters for CKD patients. However, long-term safety (in terms of mortality, cardiovascular/infection risk and tissue deposition) of high-dose intravenous iron supplementation with such high target levels of ferritin/TSAT has not been confirmed. Recently, there has been increase in the use of intravenous iron and average ferritin levels in dialysis patients in the United States. Clinical trials conducted so far have been underpowered to conclusively establish the long-term safety of intravenous iron supplementation. Results from observational studies are conflicting, and many experimental studies have even shown negative effects of intravenous iron. Clearly, randomized clinical trials are urgently needed, studying various doses of intravenous iron, with sufficient patient numbers and longer observation periods, to investigate mortality, cardiovascular effects and infection risks of this treatment. Until the long-term safety of iron supplementation at high doses is established, a more prudent decision on iron supplementation with lower target levels of ferritin/TSAT seems reasonable, in light of the decades of experience with ESA that has shown that definitive clinical outcomes have been dissociated from surrogate outcomes (especially hemoglobin concentration). PMID- 26381392 TI - Undetected residual cement on standard or individualized all-ceramic abutments with cemented zirconia single crowns - a prospective randomized pilot trial. AB - OBJECTIVE: To assess the frequency and amount of residual cement after attachment of monolithic zirconia crowns to standard and individualized ceramic abutments. MATERIAL AND METHODS: Twenty patients (mean age 58.9 years at inclusion in the study; 30% male) were randomized to receive either a standard or an individualized abutment on a bone-level implant. Monolithic zirconia single crowns were attached to abutments by use of permanent glass-ionomer cement. Crowns were fabricated with an occlusal hole to enable unscrewing of the abutment crown complex. Immediately after cementation, superstructures were removed and both the peri-implant soft tissue and the abutment-crown complex were photographed in a standardized manner, to detect residual cement. Photographs were analyzed using Corel Photo Paint X7, and residual cement-to-total abutment and residual cement-to-peri-implant soft tissue area ratios were calculated. RESULTS: Residual cement was observed for 9 of 10 (90%) individualized abutments, compared with 4 of 10 (40%) standard abutments (OR = 13.5, P = 0.049). Twenty seven of 40 (68%) individualized abutment surfaces were affected, compared with 12 of 40 (30%) standard abutment surfaces. The probability of observing residual cement was approximately five times higher for the surfaces of individualized abutments than for those of standard abutments (P = 0.005). The mean amount of sulcus surface covered by cement was 1.17% (SD 2.85) for the individualized abutments and 3.78% (SD 7.40) for the standard abutments. The position of the margin significantly affected the amount of residual cement. CONCLUSION: Both individualized and standard all-ceramic abutments result in small amounts of subgingival residual cement on abutment and sulcus surfaces. However, use of individualized abutments does not guarantee complete avoidance of undetected cement rests. Undetected residual cement might be avoided by use of all-ceramic abutments with visible abutment shoulders. PMID- 26381393 TI - Pilot Study of Natural Killer Cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis. AB - Patients with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) and multiple sclerosis (MS) suffer from debilitating fatigue which is not alleviated by rest. In addition to the fatigue-related symptoms suffered by patients with CFS/ME and MS, dysfunction of the immune system and, in particular, reduced natural killer (NK) cell cytotoxic activity has also been reported in CFS/ME and MS. The purpose of this pilot study was to compare NK cellular mechanisms in patients with CFS/ME and MS to investigate potential dysfunctions in the NK cell activity pathway. Flow cytometry protocols assessed CD56(dim) CD16(+) and CD56(bright) CD16(+/-) NK cell expression of adhesion molecules, NK activating and inhibiting receptors, NK cell maturation and lytic proteins. All participants in this study were female and included 14 patients with CFS/ME, nine patients with MS and 19 non-fatigued controls. The patient groups and the non-fatigued controls were not taking any immunosuppressive or immune-enhancing medications. In the MS cohort, KIR2DL5 was significantly increased on CD56(bright) CD16(+/-) NK cells and expression of CD94 was significantly increased on CD56(dim) CD16(+) NK cells in comparison with the controls. Co-expression of CD57 and perforin was significantly increased on CD56(dim) CD16(+) NK cells from patients with CFS/ME compared to the MS and non-fatigued control participants. The results from this pilot study suggest that NK cells from patients with CFS/ME and MS may have undergone increased differentiation in response to external stimuli which may affect different mechanisms in the NK cell cytotoxic activity pathway. PMID- 26381394 TI - Performance of processes of care and outcomes in patients with Staphylococcus aureus bacteremia. AB - BACKGROUND: Staphylococcus aureus bacteremia (SAB) is associated with significant morbidity and mortality in hospitalized adults. OBJECTIVE: We aimed to identify current practice patterns in the management of SAB, and to evaluate their association with clinical outcomes. DESIGN: Retrospective cohort study. SETTING: A 1558-bed tertiary care teaching hospital. PATIENTS: Adult patients hospitalized between January 1, 2012 through April 30, 2013, who had at least 1 positive blood culture with S aureus. INTERVENTION: None MEASUREMENTS: Electronic medical records were reviewed and the processes of care in the management of SAB were identified. The main outcome was clinical failure, defined as a composite endpoint of in-hospital mortality and persistent bacteremia. RESULTS: Two hundred fifty episodes of SAB occurred in 241 patients, and 78 (32.4%) had clinical failure. Processes of care that impacted the risk of clinical failure included: timing of follow-up blood cultures (delays of >4 days had a relative risk [RR] of 6.6; 95% confidence interval [CI]: 2.1-20.5; P = 0.001), consultation with infectious diseases specialist within 6 days from diagnosis of SAB (RR: 0.3; 95% CI: 0.1-0.9; P = 0.03), and use of beta-lactams in patients with methicillin susceptible S aureus bacteremia (RR: 0.1; 95% CI: 0.04-0.5; P = 0.002). CONCLUSIONS: The processes of care identified in our study could serve as quality and patient safety indicators for the management of SAB. PMID- 26381395 TI - Dietary restraint and impulsivity modulate neural responses to food in adolescents with obesity and healthy adolescents. AB - OBJECTIVE: Despite alarming prevalence rates, surprisingly little is known about neural mechanisms underlying eating behavior in juveniles with obesity. To simulate reactivity to modern food environments, event-related potentials (ERP) to appetizing food images (relative to control images) were recorded in adolescents with obesity and healthy adolescents. METHODS: Thirty-four adolescents with obesity (patients) and 24 matched healthy control adolescents watched and rated standardized food and object images during ERP recording. Personality (impulsivity) and eating styles (trait craving and dietary restraint) were assessed as potential moderators. RESULTS: Food relative to object images triggered larger early (P100) and late (P300) ERPs. More impulsive individuals had considerably larger food-specific P100 amplitudes in both groups. Controls with higher restraint scores showed reduced food-specific P300 amplitudes and subjective palatability ratings whereas patients with higher restraint scores showed increased P300 and palatability ratings. CONCLUSIONS: This first ERP study in adolescents with obesity and controls revealed impulsivity as a general risk factor in the current obesogenic environment by increasing food-cue salience. Dietary restraint showed paradoxical effects in patients, making them more vulnerable to visual food-cues. Salutogenic therapeutic approaches that deemphasize strict dietary restraint and foster healthy food choice might reduce such paradoxical effects. PMID- 26381396 TI - Overall Survival of Stage III Colon Cancer with Only One Lymph Node Metastasis Is Independently Predicted by Preoperative Carcinoembryonic Antigen Level and Lymph Node Sampling Status. AB - BACKGROUND: This study identified predictors of favorable overall survival (OS) for stage III colon cancer patients who had only one lymph node (LN) metastasis (N1a). METHODS: Variables, including preoperative carcinoembryonic antigen (CEA) level, LN sampling status, and the choices of postoperative adjuvant chemotherapy, were recorded. Prognostic significance was determined using the log rank test and multivariate Cox regression analysis. RESULTS: The median 42-month follow-up period included 363 eligible patients. Among them, 230 (63.3%) received only 5-flurouracil (5-FU) adjuvant chemotherapy; 76 (20.9%) underwent oxaliplatin based regimens; and 57 (15.7%) chose surgery alone. The 5-year survival rate of these evaluated patients was 75%, 63%, and 77%, respectively (P = 0.823). Multivariate analysis revealed that normal preoperative CEA level (?5 ng/mL) and adequate LN sampling (LN ? 12) were significant predictors for higher 5-year OS (P < 0.001; P = 0.007, respectively). However, the use of postoperative adjuvant chemotherapy in these N1a colon cancer patients did not significantly affect their 5-year OS. CONCLUSIONS: A preoperative CEA level of less than or equal to 5 ng/mL, and curative surgery with an adequate lymphadenectomy determined a favorable OS outcome in stage III colon cancer with only one LN metastasis. PMID- 26381397 TI - Individual Effect Modifiers of Dust Exposure Effect on Cardiovascular Morbidity. AB - BACKGROUND: High concentrations of particulate matter (PM) air pollution have been associated with death and hospital admissions due to cardiovascular morbidity. However, it is not clear a) whether high levels of non-anthropogenic PM from dust storms constitute a health risk; and b) whether these health risks are exacerbated in a particular demographic. METHODS: This study comprised all patients above 18 years old admitted to Soroka University Medical Center (1000 bed tertiary hospital, Be'er-Sheva, Israel, 2001-2010) with a primary diagnosis of acute coronary syndrome (ACS). Data on meteorological parameters and PM10 (particulate matter <10 MUm in aerodiameter) were obtained from monitoring stations in the city of Be'er-Sheva. Data were analyzed using a case crossover analysis to examine the effect of dust exposure on hospitalization due to ACS and the interaction with co-morbidities and demographic factors. RESULTS: There were 16,734 hospitalizations due to ACS during the study period. The estimated odds of hospitalization due to ACS was significantly associated with PM10 during non dust storm days at the same day of the exposure (lag0); OR = 1.014 (95%CI 1.001-1.027) for a 10 MUg/m3 increase, while a delayed response (lag1) was found during the dust storm days; OR = 1.007 (95%CI 1.002-1.012). The effect size for the dust exposure association was larger for older (above the age of 65), female or Bedouin patients. CONCLUSIONS: Exposure to non-anthropogenic PM is associated with cardiovascular morbidity. Health risk associated dust exposure is gender and age specific with older women and Bedouin patients being the most vulnerable groups. PMID- 26381398 TI - A Multiplex PCR/LDR Assay for the Simultaneous Identification of Category A Infectious Pathogens: Agents of Viral Hemorrhagic Fever and Variola Virus. AB - CDC designated category A infectious agents pose a major risk to national security and require special action for public health preparedness. They include viruses that cause viral hemorrhagic fever (VHF) syndrome as well as variola virus, the agent of smallpox. VHF is characterized by hemorrhage and fever with multi-organ failure leading to high morbidity and mortality. Smallpox, a prior scourge, has been eradicated for decades, making it a particularly serious threat if released nefariously in the essentially non-immune world population. Early detection of the causative agents, and the ability to distinguish them from other pathogens, is essential to contain outbreaks, implement proper control measures, and prevent morbidity and mortality. We have developed a multiplex detection assay that uses several species-specific PCR primers to generate amplicons from multiple pathogens; these are then targeted in a ligase detection reaction (LDR). The resultant fluorescently-labeled ligation products are detected on a universal array enabling simultaneous identification of the pathogens. The assay was evaluated on 32 different isolates associated with VHF (ebolavirus, marburgvirus, Crimean Congo hemorrhagic fever virus, Lassa fever virus, Rift Valley fever virus, Dengue virus, and Yellow fever virus) as well as variola virus and vaccinia virus (the agent of smallpox and its vaccine strain, respectively). The assay was able to detect all viruses tested, including 8 sequences representative of different variola virus strains from the CDC repository. It does not cross react with other emerging zoonoses such as monkeypox virus or cowpox virus, or six flaviviruses tested (St. Louis encephalitis virus, Murray Valley encephalitis virus, Powassan virus, Tick-borne encephalitis virus, West Nile virus and Japanese encephalitis virus). PMID- 26381399 TI - Cross-Sectional Association between Length of Incarceration and Selected Risk Factors for Non-Communicable Chronic Diseases in Two Male Prisons of Mexico City. AB - BACKGROUND: Mexico City prisons are characterized by overcrowded facilities and poor living conditions for housed prisoners. Chronic disease profile is characterized by low prevalence of self reported hypertension (2.5%) and diabetes (1.8%) compared to general population; 9.5% of male inmates were obese. There is limited evidence regarding on the exposure to prison environment over prisoner's health status; particularly, on cardiovascular disease risk factors. The objective of this study is to assess the relationship between length of incarceration and selected risk factors for non-communicable chronic diseases (NCDs). METHODS AND FINDINGS: We performed a cross-sectional analysis using data from two large male prisons in Mexico City (n = 14,086). Using quantile regression models we assessed the relationship between length of incarceration and selected risk factors for NCDs; stratified analysis by age at admission to prison was performed. We found a significant negative trend in BMI and WC across incarceration length quintiles. BP had a significant positive trend with a percentage change increase around 5% mmHg. The greatest increase in systolic blood pressure was observed in the older age at admission group. CONCLUSIONS: This analysis provides insight into the relationship between length of incarceration and four selected risk factors for NCDs; screening for high blood pressure should be guarantee in order to identify at risk individuals and linked to the prison's health facility. It is important to assess prison environment features to approach potential risk for developing NCDs in this context. PMID- 26381400 TI - Training Medical Specialists to Communicate Better with Patients with Medically Unexplained Physical Symptoms (MUPS). A Randomized, Controlled Trial. AB - BACKGROUND: Patients with medically unexplained physical symptoms (MUPS) are prevalent 25-50% in general and specialist care. Medical specialists and residents often find patients without underlying pathology difficult to deal with, whereas patients sometimes don't feel understood. We developed an evidence based communication training, aimed to improve specialists' interviewing, information-giving and planning skills in MUPS consultations, and tested its effectiveness. METHODS: The intervention group in this multi-center randomized controlled trial received a 14-hour training program to which experiential learning and feedback were essential. Using techniques from Cognitive Behavioral Therapy, they were stimulated to seek interrelating factors (symptoms, cognitions, emotions, behavior, and social environment) that reinforced a patient's symptoms. They were taught to explain MUPS understandably, reassure patients effectively and avoid unnecessary diagnostic testing. Before and after the intervention training, specialists videotaped a total of six consultations with different MUPS patients. These were evaluated to assess doctors' MUPS focused communicating skills using an adapted version of the Four Habit Coding Scheme on five-point Likert scales. Participants evaluated the training by self report on three-point Likert scales. Doctors in the control group received training after completion of the study. RESULTS: 123 doctors (40% specialists, 60% residents) and 478 MUPS patients from 11 specialties were included; 98 doctors completed the study (80%) and 449 videotaped consultations were assessed. Trained doctors interviewed patients more effectively than untrained ones (p < 0.001), summarized information in a more patient-centered way (p = 0.001), and better explained MUPS and the role of perpetuating factors (p < 0.05). No effects on planning skills were found. On a 3-point scale the training was evaluated with 2.79. CONCLUSION: MUPS-focused communication training increases the interviewing and information-giving skills of medical specialists. We recommend that the training is incorporated in postgraduate education for medical specialists and residents who frequently encounter patients with MUPS. TRIAL REGISTRATION: Dutch Trial Registration NTR2612. PMID- 26381401 TI - Attenuated Recombinant Influenza A Virus Expressing HPV16 E6 and E7 as a Novel Therapeutic Vaccine Approach. AB - Persistent infection with high-risk human papillomavirus (HPV) types, most often HPV16 and HPV18, causes all cervical and most anal cancers, and a subset of vulvar, vaginal, penile and oropharyngeal carcinomas. Two prophylactic virus-like particle (VLPs)-based vaccines, are available that protect against vaccine type associated persistent infection and associated disease, yet have no therapeutic effect on existing lesions or infections. We have generated recombinant live attenuated influenza A viruses expressing the HPV16 oncogenes E6 and E7 as experimental immunotherapeutic vaccine candidates. The influenza A virus life cycle lacks DNA intermediates as important safety feature. Different serotypes were generated to ensure efficient prime and boost immunizations. The immune response to vaccination in C57BL/6 mice was characterized by peptide ELISA and IFN-gamma ELISpot, demonstrating induction of cell-mediated immunity to HPV16 E6 and E7 oncoproteins. Prophylactic and therapeutic vaccine efficacy was analyzed in the murine HPV16-positive TC-1 tumor challenge model. Subcutaneous (s.c.) prime and boost vaccinations of mice with recombinant influenza A serotypes H1N1 and H3N2, followed by challenge with TC-1 cells resulted in complete protection or significantly reduced tumor growth as compared to control animals. In a therapeutic setting, s.c. vaccination of mice with established TC-1 tumors decelerated tumor growth and significantly prolonged survival. Importantly, intralesional vaccine administration induced complete tumor regression in 25% of animals, and significantly reduced tumor growth in 50% of mice. These results suggest recombinant E6E7 influenza viruses as a promising new approach for the development of a therapeutic vaccine against HPV-induced disease. PMID- 26381404 TI - A Comprehensive Specimen-Specific Multiscale Data Set for Anatomical and Mechanical Characterization of the Tibiofemoral Joint. AB - Understanding of tibiofemoral joint mechanics at multiple spatial scales is essential for developing effective preventive measures and treatments for both pathology and injury management. Currently, there is a distinct lack of specimen specific biomechanical data at multiple spatial scales, e.g., joint, tissue, and cell scales. Comprehensive multiscale data may improve the understanding of the relationship between biomechanical and anatomical markers across various scales. Furthermore, specimen-specific multiscale data for the tibiofemoral joint may assist development and validation of specimen-specific computational models that may be useful for more thorough analyses of the biomechanical behavior of the joint. This study describes an aggregation of procedures for acquisition of multiscale anatomical and biomechanical data for the tibiofemoral joint. Magnetic resonance imaging was used to acquire anatomical morphology at the joint scale. A robotic testing system was used to quantify joint level biomechanical response under various loading scenarios. Tissue level material properties were obtained from the same specimen for the femoral and tibial articular cartilage, medial and lateral menisci, anterior and posterior cruciate ligaments, and medial and lateral collateral ligaments. Histology data were also obtained for all tissue types to measure specimen-specific cell scale information, e.g., cellular distribution. This study is the first of its kind to establish a comprehensive multiscale data set for a musculoskeletal joint and the presented data collection approach can be used as a general template to guide acquisition of specimen specific comprehensive multiscale data for musculoskeletal joints. PMID- 26381402 TI - Mitotic Inheritance of mRNA Facilitates Translational Activation of the Osteogenic-Lineage Commitment Factor Runx2 in Progeny of Osteoblastic Cells. AB - Epigenetic mechanisms mediate the acquisition of specialized cellular phenotypes during tissue development, maintenance and repair. When phenotype-committed cells transit through mitosis, chromosomal condensation counteracts epigenetic activation of gene expression. Subsequent post-mitotic re-activation of transcription depends on epigenetic DNA and histone modifications, as well as other architecturally bound proteins that "bookmark" the genome. Osteogenic lineage commitment, differentiation and progenitor proliferation require the bone related runt-related transcription factor Runx2. Here, we characterized a non genomic mRNA mediated mechanism by which osteoblast precursors retain their phenotype during self-renewal. We show that osteoblasts produce maximal levels of Runx2 mRNA, but not protein, prior to mitotic cell division. Runx2 mRNA partitions symmetrically between daughter cells in a non-chromosomal tubulin containing compartment. Subsequently, transcription-independent de novo synthesis of Runx2 protein in early G1 phase results in increased functional interactions of Runx2 with a representative osteoblast-specific target gene (osteocalcin/BGLAP2) in chromatin. Somatic transmission of Runx2 mRNAs in osteoblasts and osteosarcoma cells represents a versatile mechanism for translational rather than transcriptional induction of this principal gene regulator to maintain osteoblast phenotype identity after mitosis. PMID- 26381405 TI - Integrin alpha6beta4 Promotes Autocrine Epidermal Growth Factor Receptor (EGFR) Signaling to Stimulate Migration and Invasion toward Hepatocyte Growth Factor (HGF). AB - Integrin alpha6beta4 is up-regulated in pancreatic adenocarcinomas where it contributes to carcinoma cell invasion by altering the transcriptome. In this study, we found that integrin alpha6beta4 up-regulates several genes in the epidermal growth factor receptor (EGFR) pathway, including amphiregulin (AREG), epiregulin (EREG), and ectodomain cleavage protease MMP1, which is mediated by promoter demethylation and NFAT5. The correlation of these genes with integrin alpha6beta4 was confirmed in The Cancer Genome Atlas Pancreatic Cancer Database. Based on previous observations that integrin alpha6beta4 cooperates with c-Met in pancreatic cancers, we examined the impact of EGFR signaling on hepatocyte growth factor (HGF)-stimulated migration and invasion. We found that AREG and EREG were required for autocrine EGFR signaling, as knocking down either ligand inhibited HGF-mediated migration and invasion. We further determined that HGF induced secretion of AREG, which is dependent on integrin-growth factor signaling pathways, including MAPK, PI3K, and PKC. Moreover, matrix metalloproteinase activity and integrin alpha6beta4 signaling were required for AREG secretion. Blocking EGFR signaling with EGFR-specific antibodies or an EGFR tyrosine kinase inhibitor hindered HGF-stimulated pancreatic carcinoma cell chemotaxis and invasive growth in three-dimensional culture. Finally, we found that EGFR was phosphorylated in response to HGF stimulation that is dependent on EGFR kinase activity; however, c-Met phosphorylation in response to HGF was unaffected by EGFR signaling. Taken together, these data illustrate that integrin alpha6beta4 stimulates invasion by promoting autocrine EGFR signaling through transcriptional up-regulation of key EGFR family members and by facilitating HGF-stimulated EGFR ligand secretion. These signaling events, in turn, promote pancreatic carcinoma migration and invasion. PMID- 26381406 TI - Structural Basis for Antigenic Peptide Recognition and Processing by Endoplasmic Reticulum (ER) Aminopeptidase 2. AB - Endoplasmic reticulum (ER) aminopeptidases process antigenic peptide precursors to generate epitopes for presentation by MHC class I molecules and help shape the antigenic peptide repertoire and cytotoxic T-cell responses. To perform this function, ER aminopeptidases have to recognize and process a vast variety of peptide sequences. To understand how these enzymes recognize substrates, we determined crystal structures of ER aminopeptidase 2 (ERAP2) in complex with a substrate analogue and a peptidic product to 2.5 and 2.7 A, respectively, and compared them to the apo-form structure determined to 3.0 A. The peptides were found within the internal cavity of the enzyme with no direct access to the outside solvent. The substrate analogue extends away from the catalytic center toward the distal end of the internal cavity, making interactions with several shallow pockets along the path. A similar configuration was evident for the peptidic product, although decreasing electron density toward its C terminus indicated progressive disorder. Enzymatic analysis confirmed that visualized interactions can either positively or negatively impact in vitro trimming rates. Opportunistic side-chain interactions and lack of deep specificity pockets support a limited-selectivity model for antigenic peptide processing by ERAP2. In contrast to proposed models for the homologous ERAP1, no specific recognition of the peptide C terminus by ERAP2 was evident, consistent with functional differences in length selection and self-activation between these two enzymes. Our results suggest that ERAP2 selects substrates by sequestering them in its internal cavity and allowing opportunistic interactions to determine trimming rates, thus combining substrate permissiveness with sequence bias. PMID- 26381407 TI - Multiple structural and epigenetic defects in the human leukocyte antigen class I antigen presentation pathway in a recurrent metastatic melanoma following immunotherapy. AB - Scant information is available about the molecular basis of multiple HLA class I antigen-processing machinery defects in malignant cells, although this information contributes to our understanding of the molecular immunoescape mechanisms utilized by tumor cells and may suggest strategies to counteract them. In the present study we reveal a combination of IFN-gamma-irreversible structural and epigenetic defects in HLA class I antigen-processing machinery in a recurrent melanoma metastasis after immunotherapy. These defects include loss of tapasin and one HLA haplotype as well as selective silencing of HLA-A3 gene responsiveness to IFN-gamma. Tapasin loss is caused by a germ-line frameshift mutation in exon 3 (TAPBP(684delA)) along with a somatic loss of the other gene copy. Selective silencing of HLA-A3 gene and its IFN-gamma responsiveness is associated with promoter CpG methylation nearby site-alpha and TATA box, reversible after DNA methyltransferase 1 depletion. This treatment combined with tapasin reconstitution and IFN-gamma stimulation restored the highest level of HLA class I expression and its ability to elicit cytotoxic T cell responses. These results represent a novel tumor immune evasion mechanism through impairing multiple components at various levels in the HLA class I antigen presentation pathway. These findings may suggest a rational design of combinatorial cancer immunotherapy harnessing DNA demethylation and IFN-gamma response. PMID- 26381408 TI - Globins Scavenge Sulfur Trioxide Anion Radical. AB - Ferrous myoglobin was oxidized by sulfur trioxide anion radical (STAR) during the free radical chain oxidation of sulfite. Oxidation was inhibited by the STAR scavenger GSH and by the heme ligand CO. Bimolecular rate constants for the reaction of STAR with several ferrous globins and biomolecules were determined by kinetic competition. Reaction rate constants for myoglobin, hemoglobin, neuroglobin, and flavohemoglobin are large at 38, 120, 2,600, and >= 7,500 * 10(6) m(-1) s(-1), respectively, and correlate with redox potentials. Measured rate constants for O2, GSH, ascorbate, and NAD(P)H are also large at ~100, 10, 130, and 30 * 10(6) m(-1) s(-1), respectively, but nevertheless allow for favorable competition by globins and a capacity for STAR scavenging in vivo. Saccharomyces cerevisiae lacking sulfite oxidase and deleted of flavohemoglobin showed an O2-dependent growth impairment with nonfermentable substrates that was exacerbated by sulfide, a precursor to mitochondrial sulfite formation. Higher O2 exposures inactivated the superoxide-sensitive mitochondrial aconitase in cells, and hypoxia elicited both aconitase and NADP(+)-isocitrate dehydrogenase activity losses. Roles for STAR-derived peroxysulfate radical, superoxide radical, and sulfo-NAD(P) in the mechanism of STAR toxicity and flavohemoglobin protection in yeast are suggested. PMID- 26381409 TI - The RNA binding complexes NF45-NF90 and NF45-NF110 associate dynamically with the c-fos gene and function as transcriptional coactivators. AB - The c-fos gene is rapidly induced to high levels by various extracellular stimuli. We used a defined in vitro transcription system that utilizes the c-fos promoter to purify a coactivator activity in an unbiased manner. We report here that NF45-NF90 and NF45-NF110, which possess archetypical double-stranded RNA binding motifs, have a direct function as transcriptional coactivators. The transcriptional activities of the nuclear factor (NF) complexes (NF45-NF90 and NF45-NF110) are mediated by both the upstream enhancer and core promoter regions of the c-fos gene and do not require their double-stranded RNA binding activities. The NF complexes cooperate with general coactivators, PC4 and Mediator, to elicit a high level of transcription and display multiple interactions with activators and the components of the general transcriptional machinery. Knockdown of the endogenous NF90/NF110 in mouse cells shows an important role for the NF complexes in inducing c-fos transcription. Chromatin immunoprecipitation assays demonstrate that the NF complexes occupy the c-fos enhancer/promoter region before and after serum induction and that their occupancies within the coding region of the c-fos gene increase in parallel to that of RNAPII upon serum induction. In light of their dynamic occupancy on the c fos gene as well as direct functions in both transcription and posttranscriptional processes, the NF complexes appear to serve as multifunctional coactivators that coordinate different steps of gene expression to facilitate rapid response of inducible genes. PMID- 26381410 TI - Distinct Cellular Assembly Stoichiometry of Polycomb Complexes on Chromatin Revealed by Single-molecule Chromatin Immunoprecipitation Imaging. AB - Epigenetic complexes play an essential role in regulating chromatin structure, but information about their assembly stoichiometry on chromatin within cells is poorly understood. The cellular assembly stoichiometry is critical for appreciating the initiation, propagation, and maintenance of epigenetic inheritance during normal development and in cancer. By combining genetic engineering, chromatin biochemistry, and single-molecule fluorescence imaging, we developed a novel and sensitive approach termed single-molecule chromatin immunoprecipitation imaging (Sm-ChIPi) to enable investigation of the cellular assembly stoichiometry of epigenetic complexes on chromatin. Sm-ChIPi was validated by using chromatin complexes with known stoichiometry. The stoichiometry of subunits within a polycomb complex and the assembly stoichiometry of polycomb complexes on chromatin have been extensively studied but reached divergent views. Moreover, the cellular assembly stoichiometry of polycomb complexes on chromatin remains unexplored. Using Sm-ChIPi, we demonstrated that within mouse embryonic stem cells, one polycomb repressive complex (PRC) 1 associates with multiple nucleosomes, whereas two PRC2s can bind to a single nucleosome. Furthermore, we obtained direct physical evidence that the nucleoplasmic PRC1 is monomeric, whereas PRC2 can dimerize in the nucleoplasm. We showed that ES cell differentiation induces selective alteration of the assembly stoichiometry of Cbx2 on chromatin but not other PRC1 components. We additionally showed that the PRC2-mediated trimethylation of H3K27 is not required for the assembly stoichiometry of PRC1 on chromatin. Thus, these findings uncover that PRC1 and PRC2 employ distinct mechanisms to assemble on chromatin, and the novel Sm-ChIPi technique could provide single-molecule insight into other epigenetic complexes. PMID- 26381413 TI - Current and Emerging Drug Targets for Human Immunodeficiency Virus. PMID- 26381414 TI - Editorial: Modulations and their Biological Functions of Protein-Biomolecule Interactions. PMID- 26381411 TI - Oligomerization and Membrane-binding Properties of Covalent Adducts Formed by the Interaction of alpha-Synuclein with the Toxic Dopamine Metabolite 3,4 Dihydroxyphenylacetaldehyde (DOPAL). AB - Oxidative deamination of dopamine produces the highly toxic aldehyde 3,4 dihydroxyphenylacetaldehyde (DOPAL), enhanced production of which is found in post-mortem brains of Parkinson disease patients. When injected into the substantia nigra of rat brains, DOPAL causes the loss of dopaminergic neurons accompanied by the accumulation of potentially toxic oligomers of the presynaptic protein alpha-synuclein (aS), potentially explaining the synergistic toxicity described for dopamine metabolism and aS aggregation. In this work, we demonstrate that DOPAL interacts with aS via formation of Schiff-base and Michael addition adducts with Lys residues, in addition to causing oxidation of Met residues to Met-sulfoxide. DOPAL modification leads to the formation of small aS oligomers that may be cross-linked by DOPAL. Both monomeric and oligomeric DOPAL adducts potently inhibit the formation of mature amyloid fibrils by unmodified aS. The binding of aS to either lipid vesicles or detergent micelles, which results in a gain of alpha-helix structure in its N-terminal lipid-binding domain, protects the protein against DOPAL adduct formation and, consequently, inhibits DOPAL-induced aS oligomerization. Functionally, aS-DOPAL monomer exhibits a reduced affinity for small unilamellar vesicles with lipid composition similar to synaptic vesicles, in addition to diminished membrane-induced alpha helical content in comparison with the unmodified protein. These results suggest that DOPAL could compromise the functionality of aS, even in the absence of protein oligomerization, by affecting the interaction of aS with lipid membranes and hence its role in the regulation of synaptic vesicle traffic in neurons. PMID- 26381415 TI - Editorial: Bioactive Small Molecules in Regulating Inflammation and Metabolic Disorder. PMID- 26381412 TI - ATDC (Ataxia Telangiectasia Group D Complementing) Promotes Radioresistance through an Interaction with the RNF8 Ubiquitin Ligase. AB - Induction of DNA damage by ionizing radiation (IR) and/or cytotoxic chemotherapy is an essential component of cancer therapy. The ataxia telangiectasia group D complementing gene (ATDC, also called TRIM29) is highly expressed in many malignancies. It participates in the DNA damage response downstream of ataxia telangiectasia-mutated (ATM) and p38/MK2 and promotes cell survival after IR. To elucidate the downstream mechanisms of ATDC-induced IR protection, we performed a mass spectrometry screen to identify ATDC binding partners. We identified a direct physical interaction between ATDC and the E3 ubiquitin ligase and DNA damage response protein, RNF8, which is required for ATDC-induced radioresistance. This interaction was refined to the C-terminal portion (amino acids 348-588) of ATDC and the RING domain of RNF8 and was disrupted by mutation of ATDC Ser-550 to alanine. Mutations disrupting this interaction abrogated ATDC induced radioresistance. The interaction between RNF8 and ATDC, which was increased by IR, also promoted downstream DNA damage responses such as IR-induced gamma-H2AX ubiquitination, 53BP1 phosphorylation, and subsequent resolution of the DNA damage foci. These studies define a novel function for ATDC in the RNF8 mediated DNA damage response and implicate RNF8 binding as a key determinant of the radioprotective function of ATDC. PMID- 26381416 TI - Focusing on the Link between Diabetes, Alzheimer's Disease and Cancer for the Discovery of New Medicines. PMID- 26381417 TI - Editorial. Recent Advances in the Structure-Based Drug Design and Discovery. PMID- 26381419 TI - Cooperative magnetic behaviour in the new valence fluctuating compound Ce2Rh3Ge. AB - In this study we report the physical properties of the new ternary compound Ce2Rh3Ge that crystallizes in the rhombohedral, triple hexagonal MgCu2-type of structure. The electronic ground state properties of Ce2Rh3Ge were characterized by magnetic susceptibility, specific heat, electrical resistivity and thermal transport measurements. The results indicate the presence of short range magnetic interaction, probably of ferromagnetic origin below T(C) = 4 K. The shape of chi(-1)(T) deviates from the Curie-Weiss behavior with a broad minimum at about T(min)(chi(-1)) = 450 K reminiscent of valence fluctuating cerium systems. At T = 10 K, the magnetic part of the resistivity rho(4 f) (T) exhibits a shallow minimum followed by increase of resistivity rho(T) ? -lnT, which hints at a substantial Kondo screening effect. Ce2Rh3Ge belongs to a small group of strongly correlated cerium compounds in which the two competing effects of Kondo and RKKY interactions produce long-range magnetic order from strongly hybridized and intermediate-valent 4 f spins. At sufficiently low temperatures Ce2Rh3Ge scales well with the Kadowaki-Woods ratio A/gamma(2) and the value of the Wilson ratio chi(T -> 0)/gamma found for this compound classifies it as a mixed-valence compound. The presence of valence fluctuation and magnetic order it is rare for these attributes to be found simultaneously in same compound, in same temperature range. In our opinion a novelty of presented results of Ce2Rh3Ge is that this compound adds a new member to a small but growing class of systems bearing a strongly mixed- or intermediate-valent 4 f magnetic moment, but in which the lattice of spins nevertheless end up finding it possible to order magnetically. PMID- 26381418 TI - H-rev107 Regulates Cytochrome P450 Reductase Activity and Increases Lipid Accumulation. AB - H-rev107 is a member of the HREV107 type II tumor suppressor gene family and acts as a phospholipase to catalyze the release of fatty acids from glycerophospholipid. H-rev107 has been shown to play an important role in fat metabolism in adipocytes through the PGE2/cAMP pathway, but the detailed molecular mechanism underlying H-rev107-mediated lipid degradation has not been studied. In this study, the interaction between H-rev107 and cytochrome P450 reductase (POR), which is involved in hepatic lipid content regulation, was determined by yeast two-hybrid screen and confirmed by using in vitro pull down assays and immunofluorescent staining. The expression of POR in H-rev107 expressing cells enhanced the H-rev107-mediated release of arachidonic acid. However, H-rev107 inhibited POR activity and relieved POR-mediated decreased triglyceride content in HtTA and HeLa cervical cells. The inhibitory effect of H rev107 will be abolished when POR-expressing cells transfected with PLA2-lacking pH-rev107 or treated with PLA2 inhibitor. Silencing of H-rev107 using siRNA resulted in increased glycerol production and reversion of free fatty acid mediated growth suppression in Huh7 hepatic cells. In summary, our results revealed that H-rev107 is also involved in lipid accumulation in liver cells through the POR pathway via its PLA2 activity. PMID- 26381421 TI - Time for a new grading system for allergic reactions? PMID- 26381420 TI - N0436 (Alliance): A Phase II Trial of Irinotecan With Cetuximab in Patients With Metastatic Breast Cancer Previously Exposed to Anthracycline and/or Taxane Containing Therapy. AB - BACKGROUND: Irinotecan has a 20% to 25% response rate (RR) in patients with previously treated metastatic breast cancer (MBC). Epidermal growth factor receptor (EGFR) is overexpressed in some MBC, especially in triple-negative breast cancer (TNBC). Cetuximab is a monoclonal antibody against EGFR with additive preclinical activity with irinotecan. PATIENTS AND METHODS: We report a 1-stage phase II study on MBC, measurable disease, and previous anthracycline and/or taxane therapy. Patients received cetuximab 400 mg/m(2) on day 1 cycle 1 then 250 mg/m(2) weekly thereafter and irinotecan 80 mg/m(2) on days 1 and 8 of each 21-day cycle. The primary end point was overall RR (ORR) according to Response Evaluation Criteria in Solid Tumors criteria (version 1.1). RESULTS: Of 19 eligible patients enrolled from February to September 2006, 14 patients (74%) had visceral disease, seven patients (37%) were hormone receptor-positive, two patients (11%) HER2-positive, and 11 patients (58%) were triple-negative. Patients received a median of 2 cycles (range, 1-37). Confirmed ORR was 11% (95% confidence interval [CI], 1%-33%), with 1 partial response and 1 complete response. One patient had stable disease for 8 months. RR for TNBC versus non TNBC was 18% versus 0% (P = .49). Median time to progression was 1.4 months (95% CI, 1.0-2.2) and median overall survival was 9.4 months (95% CI, 2.8-16.1). Twelve patients had disease progression within 2 cycles during therapy. Because of a low RR and rapid disease progression, the study leadership decided to close the trial early. CONCLUSION: The tolerability of the combination of cetuximab and irinotecan is acceptable but demonstrated low overall activity. Potentially promising results were noted in patients with TNBC and further studies of these patients might be considered. PMID- 26381422 TI - A Reference Broth Microdilution Method for Dalbavancin In Vitro Susceptibility Testing of Bacteria that Grow Aerobically. AB - Antimicrobial susceptibility testing (AST) is performed to assess the in vitro activity of antimicrobial agents against various bacteria. The AST results, which are expressed as minimum inhibitory concentrations (MICs) are used in research for antimicrobial development and monitoring of resistance development and in the clinical setting for antimicrobial therapy guidance. Dalbavancin is a semi synthetic lipoglycopeptide antimicrobial agent that was approved in May 2014 by the Food and Drug Administration (FDA) for the treatment of acute bacterial skin and skin structure infections caused by Gram-positive organisms. The advantage of dalbavancin over current anti-staphylococcal therapies is its long half-life, which allows for once-weekly dosing. Dalbavancin has activity against Staphylococcus aureus (including both methicillin-susceptible S. aureus [MSSA] and methicillin-resistant S. aureus [MRSA]), coagulase-negative staphylococci, Streptococcus pneumoniae, Streptococcus anginosus group, beta-hemolytic streptococci and vancomycin susceptible enterococci. Similar to other recent lipoglycopeptide agents, optimization of CLSI and ISO broth susceptibility test methods includes the use of dimethyl sulfoxide (DMSO) as a solvent when preparing stock solutions and polysorbate 80 (P80) to alleviate adherence of the agent to plastic. Prior to the clinical studies and during the initial development of dalbavancin, susceptibility studies were not performed with the use of P-80 and MIC results tended to be 2-4 fold higher and similarly higher MIC results were obtained with the agar dilution susceptibility method. Dalbavancin was first included in CLSI broth microdilution methodology tables in 2005 and amended in 2006 to clarify use of DMSO and P-80. The broth microdilution (BMD) procedure shown here is specific to dalbavancin and is in accordance with the CLSI and ISO methods, with step-by-step detail and focus on the critical steps added for clarity. PMID- 26381423 TI - Prevalence of and factors associated with lumbar spondylolisthesis in patients with rheumatoid arthritis. AB - OBJECTIVES: To investigate the prevalence of and elucidate risk factors for lumbar spondylolisthesis in patients with rheumatoid arthritis (RA). METHODS: From 1843 patients registered to the Akita Orthopedic Group on Rheumatoid Arthritis registry, participants comprised 128 patients who had undergone comprehensive radiographic examinations. The presence of lumbar spondylolisthesis (>=5% slip percentage) was assessed from L1 to L5 on lateral plain radiographs. At the time of radiographic evaluation, we also determined the following: RA disease duration; stage and class of Steinbrocker's classification; serum levels of C-reactive protein (CRP) and matrix metalloproteinase-3; disease activity for RA; history of joint surgery; the presence of cervical spinal instability; and details and doses of medications for RA. RESULTS: Forty-seven (36.7%) patients showed lumbar spondylolisthesis (L4, 48%; L3, 29%; L2, 13%; L5, 10%). Among these, Meyerding Grade was I in 89% and II in 11%. Multivariate analysis showed lumbar spondylolisthesis as significantly and independently associated with higher serum CRP level (odds ratio (OR), 1.50; 95% confidence interval (CI), 1.00 2.25; p = 0.048) and history of joint surgery (OR, 2.87; 95%CI, 1.22-6.72; p = 0.015). CONCLUSIONS: More than one-third of patients with RA in this cohort had lumbar spondylolisthesis, and significant associations with higher serum CRP levels and history of joint surgery were identified. PMID- 26381424 TI - Proteolytic Isoforms of SPARC Induce Adipose Stromal Cell Mobilization in Obesity. AB - Adipose stromal cells (ASC) are mesenchymal adipocyte progenitors that reside in the peri-endothelium of fat tissue. ASC mobilization and migration accompany white adipose tissue (WAT) remodeling and pathological conditions. Mechanisms regulating ASC trafficking are largely unknown. We previously reported that binding of the matricellular protein secreted protein acidic and rich in cysteine (SPARC) to beta1 integrin on ASC surface induces their motility. Here, we show that SPARC is required for ASC mobilization. We report two SPARC proteolytic isoforms, C-SPARC (lacking the N terminus) and N-SPARC (lacking the C terminus), generated in mesenteric WAT of obese mice. C-SPARC, but not N-SPARC, binds to beta1 integrin on ASC, while N-SPARC preferentially binds to the extracellular matrix (ECM) and blocks ECM/integrin interaction. Interestingly, both C-SPARC and N-SPARC induce ASC deadhesion from the ECM, which is associated with modulation of integrin-dependent FAK-ERK signaling and integrin-independent ILK-Akt signaling. We show that these SPARC isoforms, acting on ASC through distinct mechanisms, have an additive effect in inducing ASC migration. PMID- 26381425 TI - Electrochemical enzyme-less urea sensor based on nano-tin oxide synthesized by hydrothermal technique. AB - Nano-Tin oxide was synthesized using hydrothermal method at 150 degrees C for 6 h and then thin films were deposited by electrophoretic method at an optimized voltage of 100 V for 5 min on electropolished aluminum substrate. Spherical particles of about 30-50 nm diameters are observed with partial agglomeration when observed under electron microscope, which are tetragonal rutile structure. XPS results showed peaks related to Sn 4d, Sn 3d, O 1s & C 1s with spin-orbit splitting of 8.4 eV for Sn 3d. Feasibility studies of enzyme less urea sensing characteristics of nano-tin oxide thin films are exhibited herein. The deposited films have been used for enzyme less urea sensing from 1 to 20 mM concentration in buffer solution. The sensors were characterized electrochemically to obtain cyclic voltammogram as a function of urea concentration and scan rate. The sensitivity is estimated as 18.9 MUA/mM below 5 mM and 2.31 MUA/mM above 5 mM with a limit of detection of 0.6 mM. PMID- 26381426 TI - Standardization of patellofemoral morphology in the pediatric knee. AB - BACKGROUND: Our understanding of osseous morphology and pathology of the patellofemoral joint continues to improve with the use of magnetic resonance imaging (MRI), but a paucity of data currently exists in the pediatric population. OBJECTIVE: We aim to formulate a reproducible means of quantitative assessment of patellofemoral morphology in children using MRI and to describe morphological changes based on sex and age. MATERIALS AND METHODS: We identified 414 children presenting between 2002 and 2014 who obtained a knee MRI to evaluate for knee pain or clinically suspected knee pathology. After application of inclusion criteria, 144 "normal" MRIs in 131 children (71 boys, 60 girls) were included in the analysis. The following MRI measurements were recorded: lateral trochlear inclination, trochlear facet asymmetry, trochlear depth, tibial tuberosity-trochlear groove distance, sulcus angle and patellar height ratio. To assess intraobserver reliability, measurements in 30 randomly selected children were repeated. Differences between patient age and sex were assessed using independent t-tests and adjusted regression analysis. RESULTS: All recorded measurements had strong to very strong inter- and intraobserver reliability: lateral trochlear inclination (0.91/0.82), trochlear facet asymmetry (0.81/0.83), trochlear depth (0.83/0.90), tibial tuberosity-trochlear groove distance (0.97/0.87), sulcus angle (0.84/0.78) and patellar height ratio (0.96/0.83). When age and sex were mutually adjusted, statistically significant differences between males and females were observed in trochlear depth (P = 0.0084) and patellar height ratio (P = 0.0035). However, statistically significant age differences were found on all measurements except for lateral trochlear inclination. As expected, mean measurement values approached adult norms throughout skeletal maturation suggestive of age-dependent patellofemoral maturation. CONCLUSION: Our data verify the development of patellofemoral morphology with advancing age. We found that six of the most commonly used patellofemoral measurements in adults can be accurately reproduced regardless of age. PMID- 26381427 TI - Measuring the impact of guideline-based antiemetic therapy on nausea and vomiting control in breast cancer patients with multiple risk factors. AB - PURPOSE: The objective of this exploratory analysis was to determine if individual patient risk factors could be used to optimize chemotherapy-induced nausea and vomiting (CINV). METHODS: Through validated risk prediction models which quantify patient risk factors, 152 patients with early-stage breast cancer scheduled to received adjuvant anthracycline-based chemotherapy were categorized as being at low (level 0) or high-risk (level 1) for CINV. Prior to the first cycle of chemotherapy, low-risk patients received ondansetron and dexamethasone, while high-risk level 1 patients also received aprepitant. For subsequent cycles, patients who experienced CINV had their antiemetics changed in a stepwise manner to level 2 (extended-duration dexamethasone) or level 3 (extended-duration dexamethasone and low-dose olanzapine). RESULTS: The study enrolled 152 patients who received 484 cycles of chemotherapy. Forty patient cycles were classified as low risk (level 0) compared to 201, 162 and 81 that were classified as high-risk levels 1, 2 and 3, respectively. Complete control of acute and delayed vomiting was comparable and was achieved in over 85 % of patients across all risk levels (p = 0.56 and p = 0.99). In contrast, complete control of acute and delayed nausea was reduced in risk levels 1 to 3 compared to level 0 (acute = 51.2, 58.0, 45.7 vs. 70.0 %; p = 0.013)-(delayed = 32.8, 45.7, 34.6 vs. 62.5 %; p < 0.001). CONCLUSIONS: Despite the addition of aprepitant, extended-duration dexamethasone and olanzapine, patients at high risk for CINV due to personal risk factors failed to achieve good nausea control. PMID- 26381428 TI - Neuronal Nitric Oxide Synthase-Mediated Genotoxicity of 2-Methoxyestradiol in Hippocampal HT22 Cell Line. AB - 2-methoxyestradiol, metabolite of 17beta-estradiol, is considered a potential anticancer agent, currently investigated in several clinical trials. This natural compound was found to be effective towards great number of cancers, including colon, breast, lung, and osteosarcoma and has been reported to be relatively non toxic towards non-malignant cells. The aim of the study was to determine the potential neurotoxicity and genotoxicity of 2-methoxyestradiol at physiological and pharmacological relevant concentrations in hippocampal HT22 cell line. Herein, we determined influence of 2-methoxyestradiol on proliferation, inhibition of cell cycle, induction of apoptosis, and DNA damage in the HT22 cells. The study was performed using imaging cytometry and comet assay techniques. Herein, we demonstrated that 2-methoxyestradiol, at pharmacologically and also physiologically relevant concentrations, increases nuclear localization of neuronal nitric oxide synthase. It potentially results in DNA strand breaks and increases in genomic instability in hippocampal HT22 cell line. Thus, we are postulating that naturally occurring 2-methoxyestradiol may be considered a physiological modulator of neuron survival. PMID- 26381429 TI - Inflammation Promotes a Conversion of Astrocytes into Neural Progenitor Cells via NF-kappaB Activation. AB - Brain inflammation, a common feature in neurodegenerative diseases, is a complex series of events, which can be detrimental and even lead to neuronal death. Nonetheless, several studies suggest that inflammatory signals are also positively influencing neural cell proliferation, survival, migration, and differentiation. Recently, correlative studies suggested that astrocytes are able to dedifferentiate upon injury and may thereby re-acquire neural stem cell (NSC) potential. However, the mechanism underlying this dedifferentiation process upon injury remains unclear. Here, we report that during the early response of reactive gliosis, inflammation induces a conversion of mature astrocytes into neural progenitors. A TNF treatment induces the decrease of specific astrocyte markers, such as glial fibrillary acidic protein (GFAP) or genes related to glycogen metabolism, while a subset of these cells re-expresses immaturity markers, such as CD44, Musashi-1, and Oct4. Thus, TNF treatment results in the appearance of cells that exhibit a neural progenitor phenotype and are able to proliferate and differentiate into neurons and/or astrocytes. This dedifferentiation process is maintained as long as TNF is present in the culture medium. In addition, we highlight a role for Oct4 in this process, since the TNF induced dedifferentiation can be prevented by inhibiting Oct4 expression. Our results show that activation of the NF-kappaB pathway through TNF plays an important role in the dedifferentiation of astrocytes via the re-expression of Oct4. These findings indicate that the first step of reactive gliosis is in fact a dedifferentiation process of resident astrocytes mediated by the NF-kappaB pathway. PMID- 26381430 TI - Longitudinal Patterns of Stages of Change for Exercise and Lifestyle Intervention Outcomes: An Application of Latent Class Analysis with Distal Outcomes. AB - Stages of change measure an individual's readiness to alter a health behavior. This study examined the latent longitudinal patterns of stages of change (SoC) for regular exercise over time among individuals participating in a lifestyle intervention project. It also investigated the association between the longitudinal patterns of SoC and intervention outcomes using a new statistical method to assess the relationship between latent class membership and distal outcomes. We analyzed data from the Special Diabetes Program for Indians Diabetes Prevention Program, a lifestyle intervention program to prevent diabetes among American Indians and Alaska Natives. Latent class analysis (LCA) was conducted to identify the longitudinal patterns of SoC for regular exercise reported at three time points. LCA with distal outcomes was performed to investigate the associations between latent class membership and behavioral changes after the intervention. The parameters and standard errors of the LCA with distal outcomes models were estimated using an improved three-step approach. Three latent classes were identified: Pre-action, Transition, and Maintenance classes. The Transition class, where stage progression occurred, had the greatest improvements in physical activity and weight outcomes at both time points post-baseline among female participants. It also had the largest improvements in weight outcomes among male participants. Furthermore, the Pre-action class had more attenuation in the improvements they had achieved initially than the other two classes. These findings suggest the potential importance of motivating participants to modify their readiness for behavioral change in future lifestyle interventions. PMID- 26381431 TI - Knowledge Lability: Within-Person Changes in Parental Knowledge and Their Associations with Adolescent Problem Behavior. AB - Higher levels of parental knowledge about youth activities have been associated with lower levels of youth risky behavior. Yet little is known about how parental knowledge fluctuates during early adolescence and how those fluctuations are associated with the development of problem behavior. We use the term lability to describe within-person fluctuations in knowledge over time with higher lability indicating greater fluctuations in knowledge from year-to-year. This longitudinal study of rural adolescents (N = 840) investigated if change in parental knowledge across four waves of data from grades 6 to 8 is characterized by lability, and if greater lability is associated with higher youth substance use, delinquency, and internalizing problems in grade 9. Our models indicated that only some of the variance in parental knowledge was accounted for by developmental trends. The remaining residual variance reflects within-person fluctuations around these trends, lability, and measurement and occasion-specific error. Even controlling for level and developmental trends in knowledge, higher knowledge lability (i.e., more fluctuation) was associated with increased risk for later alcohol and tobacco use, and for girls, higher delinquency and internalizing problems. Our findings suggest that lability in parental knowledge has unique implications for adolescent outcomes. The discussion focuses on mechanisms that may link knowledge lability to substance use. Interventions may be most effective if they teach parents to consistently and predictably decrease knowledge across early adolescence. PMID- 26381432 TI - The prevalence of mild cognitive impairment with type 2 diabetes mellitus among elderly people in China: A cross-sectional study. AB - BACKGROUND: In absence of curative treatments for dementia with type 2 diabetes mellitus (T2DM), mild cognitive impairment (MCI) in T2DM, the preclinical transitional states of dementia with T2DM has attracted dramatic attention. Our study was to estimate the prevalence and distribution of MCI in T2DM subjects from China, and identify influencing factors of subjects in MCI with T2DM. METHODS: In the present study, we performed cluster random sampling of 8213 people aged 65 years and older in Tianjin, a metropolitan city, located in northern China. All participants were interviewed and screened for T2DM. 1109 subjects with T2DM were initially screened with American Diabetes Association criteria for diagnosis of diabetes mellitus and were diagnosed with MCI and dementia according to the criteria of DSM-IIIR. The prevalence of MCI and dementia in subjects with T2DM were compared with that in ordinary subjects. Logistic regression analyses were performed to evaluate risk of MCI with T2DM. RESULTS: Among all 8213 subjects, overall MCI and dementia with T2DM prevalence were 13.5% and 2.34%, respectively. Compared with ordinary subjects, the prevalence of MCI in the present study was more frequent than the prevalence of MCI for the general population in almost each age group. In the univariate analyses, among all diabetic subjects, compared with cognitive intactly subjects, MCI subjects had significantly higher levels of age, current smoking, mean waist circumference, duration from onset of diabetes, insulin intake, systolic BP, fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c) and immunoreactive insulin (IRI). In multivariate logistic regression analyses, variables including current smoking, duration from onset of diabetes, FPG, HbA1c and IRI were significantly associated with increased risk for MCI with T2DM, the ORs were 1.36,1.33,1.17,1.25 and 1.33, respectively (all P<0.05). CONCLUSIONS: The present study confirms the high prevalence of MCI with T2DM among the elderly population of China. T2DM is related to a higher risk of MCI in a population with a high prevalence of this disorder and may aggravate the clinical picture as a concomitant factor. PMID- 26381434 TI - Estimation of the prevalence of latent tuberculosis infection in patients with moderate to severe plaque psoriasis in Spain: The Latent study. AB - BACKGROUND AND OBJECTIVE: Anti-tumor necrosis factor therapy for moderate to severe psoriasis can increase the risk of active tuberculosis in patients who have latent tuberculosis infection (LTBI). The main objective of this study was to estimate the prevalence of LTBI in patients with moderate to severe plaque psoriasis being treated in dermatology clinics in Spain. MATERIAL AND METHOD: Non interventional, cross-sectional, national epidemiological study conducted in Spain in 2011-2012. Patients with moderate to severe plaque psoriasis were included if they had undergone at least one tuberculin skin test (TST) and/or been evaluated with an interferon-gamma release assay (IGRA) based on enzyme linked immunosorbent assay (QuantiFERON((r)) TB Gold In-Tube) in the 2 years preceding the study. RESULTS: Data for 440 patients were valid for analysis. In total, 97.7% of the patients had undergone a TST, with a positive result in 23%. Of the 238 patients in whom the initial result was negative, 5% converted to positive on re-testing for a booster effect. IGRA results were available for 16.8%, 20.5% of them positive. Two of the patients with positive IGRA results had a negative TST. The prevalence of LTBI in the whole sample was 26.6%. The degree of concordance between the TST and the IGRA was moderate (kappa=0.516; P<.001). CONCLUSIONS: The prevalence of LTBI in this study was similar to previous estimates for Spain. PMID- 26381433 TI - Minocycline Attenuates Depressive-Like Behaviour Induced by Rat Model of Testicular Torsion: Involvement of Nitric Oxide Pathway. AB - Testicular torsion/detorsion (T/D) can induce depression in pre- and post pubertal patients. This study was conducted to investigate the psychological impact of testicular torsion and mechanism underlying its depressive-like behaviour, as well as antidepressant-like activity of minocycline and possible involvement of nitric oxide (NO)/cyclic GMP pathway in this paradigm in male rats undergoing testicular T/D. Unilateral T/D was performed in 36 male adult Wistar rats, and different doses of minocycline were injected alone or combined with N(omega) -nitro-l-arginine methyl ester (l-NAME), non-specific NO synthase (NOS) inhibitor; aminoguanidine (AG), specific inducible NOS inhibitor; l-arginine, an NO precursor; and selective PDE5I, sildenafil. After assessment of locomotor activity in open-field test, immobility times were recorded in the forced swimming test (FST). Moreover, 30 days after testicular T/D, testicular venous testosterone and serum nitrite concentrations were measured. A correlation was observed between either a decrease in plasma testosterone or an increase in serum nitrite concentrations with prolongation in immobility time in the testicular T/D operated rats FST. Minocycline (160 mg/kg) exerted the highest significant antidepressant-like effect in the operated rats in the FST (p < 0.001). Furthermore, combination of subeffective doses of minocycline (80 mg/kg) and either l-NAME (10 mg/kg) or AG (50 mg/kg) demonstrated a significant robust antidepressant-like activity in T/D group (p < 0.01). Consequently, NO/cGMP pathway was involved in testicular T/D-induced depressive-like behaviour and antidepressant-like activity of minocycline in the animal model. Moreover, a contribution was observed between either decreased testosterone or elevated serum nitrite levels and depressive-like behaviour following testicular T/D. PMID- 26381435 TI - Surgical training should specifically include training in day case surgery. PMID- 26381436 TI - Chronic immune thrombocytopenia and semaphorin 5A. PMID- 26381437 TI - Role of protein kinase CK2 in the dynamic interaction of platelets, leukocytes and endothelial cells during thrombus formation. AB - INTRODUCTION: Thrombus formation is a complex process, which is characterized by the dynamic interaction of platelets, leukocytes and endothelial cells. The activation of these cells is strictly mediated by different phospho-regulated signaling pathways. Recently, it has been reported that inhibition of protein kinase CK2 affects platelet function by suppressing phosphatidylinositol-4,5 bisphosphate-3-kinase (PI3K) signaling. Based on this finding, we herein analyzed whether CK2 acts as a crucial regulator of thrombus formation. MATERIALS AND METHODS: We examined the effect of CK2 inhibition on platelet activation and aggregation, the formation of platelet-leukocyte aggregates (PLA), the endothelial expression of von Willebrand factor (vWF), intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1, and the subcellular localization of nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) and phospho-p65 in human dermal microvascular endothelial cells (HDMEC). Dorsal skinfold chambers were prepared in BALB/c mice to analyze in vivo the effect of CK2 inhibition on photochemically induced thrombus formation using intravital fluorescence microscopy. RESULTS: CK2 inhibition by CX-4945 suppressed adenosin diphosphate (ADP)- and proteinase-activated receptor-1-peptide (PAR-1 AP)-stimulated platelet aggregation, which was associated with down-regulation of P-selectin, GPIIb/IIIa and a reduced formation of PLA. Expression and secretion of vWF was diminished in CX-4945-treated HDMEC. Moreover, CK2 inhibition attenuated the endothelial expression of VCAM-1, whereas the expression of ICAM-1 was not affected. Finally, CX-4945-treated mice exhibited a significantly delayed photochemically induced thrombus formation when compared to vehicle-treated controls. CONCLUSION: These results indicate that CK2 is a pleiotropic regulator of thrombus formation, affecting multiple interactions of platelets, leukocytes and endothelial cells. PMID- 26381438 TI - Probabilistic reward- and punishment-based learning in opioid addiction: Experimental and computational data. AB - Addiction is the continuation of a habit in spite of negative consequences. A vast literature gives evidence that this poor decision-making behavior in individuals addicted to drugs also generalizes to laboratory decision making tasks, suggesting that the impairment in decision-making is not limited to decisions about taking drugs. In the current experiment, opioid-addicted individuals and matched controls with no history of illicit drug use were administered a probabilistic classification task that embeds both reward-based and punishment-based learning trials, and a computational model of decision making was applied to understand the mechanisms describing individuals' performance on the task. Although behavioral results showed that opioid-addicted individuals performed as well as controls on both reward- and punishment-based learning, the modeling results suggested subtle differences in how decisions were made between the two groups. Specifically, the opioid-addicted group showed decreased tendency to repeat prior responses, meaning that they were more likely to "chase reward" when expectancies were violated, whereas controls were more likely to stick with a previously-successful response rule, despite occasional expectancy violations. This tendency to chase short-term reward, potentially at the expense of developing rules that maximize reward over the long term, may be a contributing factor to opioid addiction. Further work is indicated to better understand whether this tendency arises as a result of brain changes in the wake of continued opioid use/abuse, or might be a pre-existing factor that may contribute to risk for addiction. PMID- 26381439 TI - Inflammatory monocyte gene expression: trait or state marker in bipolar disorder? AB - BACKGROUND: This study aimed to examine whether inflammatory gene expression was a trait or a state marker in patients with bipolar disorder (BD). METHODS: 69 healthy controls (HC), 82 euthymic BD patients and 8 BD patients with a mood episode (7 depressed, 1 manic) were included from the MOODINFLAME study. Six of the eight patients who had a mood episode were also investigated when they were euthymic (6 of the 82 euthymic patients). Of these participants the expression of 35 inflammatory genes was determined in monocytes using quantitative-polymerase chain reaction, of which a total gene expression score was calculated as well as a gene expression score per sub-cluster. RESULTS: There were no significant differences in inflammatory monocyte gene expression between healthy controls and euthymic patients. Patients experiencing a mood episode, however, had a significantly higher total gene expression score (10.63 +/- 2.58) compared to healthy controls (p = .004) and euthymic patients (p = .009), as well as when compared to their own scores when they were euthymic (p = .02). This applied in particular for the sub-cluster 1 gene expression score, but not for the sub cluster 2 gene expression score. CONCLUSIONS: Our study indicates that in BD inflammatory monocyte, gene expression is especially elevated while in a mood episode compared to being euthymic. PMID- 26381440 TI - Experimental evidence of hepatitis A virus infection in pigs. AB - Hepatitis A virus (HAV) is the leading cause of acute viral hepatitis worldwide, with HAV infection being restricted to humans and nonhuman primates. In this study, HAV infection status was serologically determined in domestic pigs and experimental infections of HAV were attempted to verify HAV infectivity in pigs. Antibodies specific to HAV or HAV-like agents were detected in 3.5% of serum samples collected from pigs in swine farms. When the pigs were infected intravenously with 2 * 10(5) 50% tissue culture infectious dose (TCID50 ) of HAV, shedding of the virus in feces, viremia, and seroconversion were detected. In pigs orally infected with the same quantity of HAV, viral shedding was detected only in feces. HAV genomic RNA was detected in the liver and bile of intravenously infected pigs, but only in the bile of orally infected pigs. In further experiments, pigs were intravenously infected with 6 * 10(5) TCID50 of HAV. Shedding of HAV in feces, along with viremia and seroconversion, were confirmed in infected pigs but not in sentinel pigs. HAV genomic RNA was detected in the liver, bile, spleen, lymph node, and kidney of the infected pigs. HAV antigenomic RNA was detected in the spleen of one HAV-infected pig, suggesting HAV replication in splenic cells. Infiltration of inflammatory cells was observed in the livers of infected pigs but not in controls. This is the first experimental evidence to demonstrate that human HAV strains can infect pigs. PMID- 26381441 TI - Biomimetic [2Fe-2S] clusters with extensively delocalized mixed-valence iron centers. AB - A complete series of biomimetic [2Fe-2S] clusters, [(L(Dep) Fe)2 (MU-S)2 ] (3, L(Dep) =CH[CMeN(2,6-Et2 C6 H3 )]2 ), [(L(Dep) Fe)2 (MU-S)2 K] (4), [(L(Dep) Fe)2 (MU-S)2 ][Bu4 N] (5, Bu=n-butyl), and [(L(Dep) Fe)2 (MU-S)2 K2 ] (6), could be synthesized and characterized. The all-ferric [2Fe-2S] cluster 3 is readily accessible through the reaction of [(L(Dep) Fe)2 (MU-H)2 ] (2) with elemental sulfur. The chemical reduction of 3 with one molar equivalent of elemental potassium affords the contact ion pair K(+) [2Fe-2S](-) (4) as a one-dimensional coordination polymer, which in turn reacts with [Bu4 N]Cl to afford the separate ion pair [Bu4 N](+) [2Fe-2S](-) (5). Further reduction of 4 with potassium furnishes the super-reduced all-ferrous [2Fe-2S] cluster 6. Remarkably, complexes 4 and 5 are [2Fe-2S] clusters with extensively delocalized Fe(2+) Fe(3+) pairs as evidenced by (57) Fe Mossbauer, X-ray absorption and emission spectroscopy (XAS, XES) and in accordance with DFT calculations. PMID- 26381442 TI - Does promoting parents' negative attitudes to underage drinking reduce adolescents' drinking? The mediating process and moderators of the effects of the Orebro Prevention Programme. AB - BACKGROUND AND AIMS: The Orebro Prevention Programme (OPP) was found previously to be effective in reducing drunkenness among adolescents [Cohen's d = 0.35, number needed to treat (NNT) = 7.7]. The current study tested the mediating role of parents' restrictive attitudes to underage drinking in explaining the effectiveness of the OPP, and the potential moderating role of gender, immigration status, peers' and parents' drinking and parent-adolescent relationship quality. DESIGN: A quasi-experimental matched-control group study with assessments at baseline, and at 18- and 30-month follow-ups. PARTICIPANTS: Of the 895 target youths at ages 12-13 years, 811 youths and 651 parents at baseline, 653 youths and 524 parents at 18-month and 705 youths and 506 parents at 30-month follow-up participated in the study. MEASUREMENTS: Youths reported on their past month drunkenness, their parents' and peers' alcohol use and the quality of their relationship with parents. Parents reported on their attitudes to underage drinking. FINDINGS: The mediation analyses, using latent growth curve modeling, showed that changes in parents' restrictive attitudes to underage drinking explained the impact of the OPP on changes in youth drunkenness, which was reduced, and onset of monthly drunkenness, which was delayed, relative to controls. Mediation effect explained 57 and 45% of the effects on drunkenness and onset of monthly drunkenness, respectively. The programme effects on both parents' attitudes and youth drunkenness were similar across gender, immigrant status, parents' and peers' alcohol use and parent-youth relationship quality. CONCLUSIONS: Increasing parents' restrictive attitudes to youth drinking appears to be an effective and robust strategy for reducing heavy underage drinking regardless of the adolescents' gender, cultural origin, peers' and parents' drinking and relationship quality with parents. PMID- 26381443 TI - Ureteric stent left in situ for 27 years. PMID- 26381444 TI - Identification of a vertically transmitted strain from Anaplasma marginale (UFMG3): Molecular and phylogenetic characterization, and evaluation of virulence. AB - Bovine anaplasmosis is a disease caused by the intraerythrocytic rickettsia species Anaplasma marginale and results in great economic losses in tropical and subtropical regions. Vertical transmission is an important phenomenon that contributes to the persistence of different strains of the agent within the same herd. The identification of new strains and genetic characterization studies are essential to understanding their epidemiology and virulence and for vaccine development. The aim of this study was to perform molecular and phylogenetic characterizations of a new vertically transmitted strain from A. marginale and to evaluate its virulence by experimental inoculation of rickettsia-free calves. Thirty newborn Holstein calves were subjected to molecular tests for the detection of A. marginale, Babesia bovis and Babesia bigemina. Calves positive for A. marginale (n=3) were splenectomized and monitored for the clinical manifestations of anaplasmosis. Blood samples from one of the calves that presented rickettsemia of 42.8% and spontaneous recovery of clinical parameters were used for molecular and phylogenetic characterization (msp1a gene), and inoculum production was used for the evaluation of virulence. This strain was identified as UFMG3. Three tandem repeat forms (13 and MGI19) were identified from the analysis of the msp1a gene, in which the form MGI19 appeared twice. Analysis of these repeats revealed the presence of the sequences QASTSS and SSASGQQQESS and of aspartic acid (D) at position 20 of both repeats. Phylogenetic analysis showed a close relationship among the UFMG3, MGI19 and UFMG2 strains. For virulence evaluation, six Holstein calves were inoculated intravenously with 2*10(7)A. marginale UFMG3-infected erythrocytes. The calves showed maximum rickettsemia of 5.1%, a moderate decrease in packed cell volume and spontaneous recovery of clinical parameters without the need for treatment. The results of experimental inoculation suggest that the strain A. marginale UFMG3 has low virulence and potential application for use as a live vaccine against A. marginale. PMID- 26381445 TI - Coronary atherosclerosis: An intra or extra luminal disease? PMID- 26381446 TI - Immunoglobulin G4-associated autoimmune hepatitis later complicated by autoimmune pancreatitis: A case report. AB - Immunoglobulin G4 (IgG4)-associated autoimmune hepatitis (AIH) is a new disease entity with elevated levels of serum IgG4 and marked IgG4 positive plasma cell infiltration of the liver, and its clinical course remains unknown. A patient with IgG4-associated AIH who later developed autoimmune pancreatitis (AIP) is reported. A 73-year-old man was admitted to our hospital due to elevated liver transaminase levels, hypergammaglobulinemia and positive antinuclear antibody. A liver biopsy specimen showed severe interface hepatitis with marked lymphoplasmacytic infiltration without damage to the interlobular bile ducts, and a diagnosis of AIH was made. Abdominal computed tomography showed no abnormalities in the pancreas. Prednisolone therapy normalized the transaminase levels. Two years later, the patient developed AIP, which recurred after 5 years due to a reduction in the prednisolone dose. Three years later, he had a recurrence of AIH after discontinuation of prednisolone treatment. Evaluation of serum IgG4 levels and IgG4-bearing plasma cell infiltration of the liver at both the onset and recurrence of AIH showed that the serum IgG4 levels were 284 and 208 mg/dL, respectively, and the IgG4-bearing plasma cell infiltration levels were 30-40 cells/high-power field (HPF) per portal area and 4-10 cells/HPF per portal area, respectively. From these results, this case was finally diagnosed as IgG4-associated AIH. The course of this patient demonstrates two important clinical lessons: (i) IgG4-associated AIH can later be complicated by AIP; and (ii) discontinuation of prednisolone treatment can cause recurrence of IgG4 associated AIH. PMID- 26381447 TI - Letter to the Editor regarding "Systematic review of flexion/extension radiography of the cervical spine in trauma patients". PMID- 26381448 TI - Evidence for effects on thermoregulation after acute oral exposure to type I and type II pyrethroids in infant rats. AB - Most pyrethroid (PYR) insecticides may be classified either as type-I compounds, which produce whole body tremors and hyperthermia, or type-II compounds, which produce salivation, choreoathetosis, and hypothermia (i.e., producing T and CS neurobehavioral syndromes, respectively). This classification is based on clinical observations in adult rats and mice after intracerebroventricular or intravascular administration of highly effective acute (bolus) doses. PYR neurotoxicity in infant animals is not characterized as much as in adult animals. Endpoints informing on vital determinants of mammal's maturation, such as body temperature may help recognizing age-related differences in susceptibility to PYRs. In this work, body temperature (Tb) was monitored at 30-min intervals after acute oral exposure to T-syndrome PYR bifenthrin (BIF), CS-syndrome PYR cypermethrin (CYPM), and a BIF-CYPM mixture in weanling rats by using a subcutaneous temperature monitoring system. In both single-compound assays, a time- and dose-related decline of Tb was the most evident impact on thermoregulation observed starting at ~2-3 h after dosing.Moreover, 15-18 mg/kg BIF induced a mild increase in Tb before the hypothermic action was apparent. The lowest effective dose for temperature perturbation was 15mg/kg for BIF and 10mg/kg for CYPM, and moderate neurobehavioral alterations were evident at 12 and 10mg/kg, respectively. When low effective doses of BIF and CYPM were co administered mild behavioral effects and a transient increase in Tb (p=0.02) were observed at 1-2 h, and no Tb decline was apparent afterwards compared to control animals. Noteworthy, the hypothermic action of BIF in infant rats was quite different from the hyperthermia consistently reported in studies using mature animals. Our results suggest that body temperature monitoring may be useful as a complementary assessment to reveal qualitative age-specific pesticide effects in rats. PMID- 26381450 TI - Direct-Writing of Cu Nano-Patterns with an Electron Beam. AB - We demonstrate direct electron beam writing of a nano-scale Cu pattern on a surface with a thin aqueous layer of CuSO4 solution. Electron beams are highly maneuverable down to nano-scales. Aqueous solutions facilitate a plentiful metal ion supply for practical industrial applications, which may require continued reliable writing of sophisticated patterns. A thin aqueous layer on a surface helps to confine the writing on the surface. For this demonstration, liquid sample holder (K-kit) for transmission electron microscope (TEM) was employed to form a sealed space in a TEM. The aqueous CuSO4 solution inside the sample holder was allowed to partially dry until a uniform thin layer was left on the surface. The electron beam thus reduced Cu ions in the solution to form the desired patterns. Furthermore, the influence of e-beam exposure time and CuSO4(aq) concentration on the Cu reduction was studied in this work. Two growth stages of Cu were shown in the plot of Cu thickness versus e-beam exposure time. The measured Cu reduction rate was found to be proportional to the CuSO4(aq) concentration. PMID- 26381449 TI - The association of DNA methylation and brain volume in healthy individuals and schizophrenia patients. AB - Both methylation and brain volume patterns hold important biological information for the development and prognosis of schizophrenia (SZ). A combined study to probe the association between them provides a new perspective to understanding SZ. Genomic methylation of peripheral blood and regional brain volumes derived from magnetic resonance imaging were analyzed using parallel independent component analyses in this study. Nine methylation components and five brain volumetric components were extracted for 94 SZ patients and 106 healthy controls. After controlling for age, sex, race, and substance use, a component comprised primarily of bilateral cerebellar volumes was significantly correlated to a methylation component from 14 CpG sites in 13 genes. Both patients and healthy controls demonstrated similar associations, but patients had significantly smaller cerebellar volumes and dysmethylation in the associated epigenetic component compared to controls. The 13 genes are enriched in cellular growth and proliferation with some genes involved in neuronal growth and cerebellum development (GATA4, ADRA1D, EPHA3, and KCNK10), and these genes are prominently associated with neurological and psychological disorders. Such findings suggest that the methylation pattern of the genes coding for cellular growth may influence the cerebellar development through regulating gene expression, and the alteration in the methylation of these genes in SZ patients may contribute to the cerebellar volume reduction observed in patients. PMID- 26381451 TI - Discovery of Novel Allosteric Non-Bisphosphonate Inhibitors of Farnesyl Pyrophosphate Synthase by Integrated Lead Finding. AB - Farnesyl pyrophosphate synthase (FPPS) is an established target for the treatment of bone diseases, but also shows promise as an anticancer and anti-infective drug target. Currently available anti-FPPS drugs are active-site-directed bisphosphonate inhibitors, the peculiar pharmacological profile of which is inadequate for therapeutic indications beyond bone diseases. The recent discovery of an allosteric binding site has paved the way toward the development of novel non-bisphosphonate FPPS inhibitors with broader therapeutic potential, notably as immunomodulators in oncology. Herein we report the discovery, by an integrated lead finding approach, of two new chemical classes of allosteric FPPS inhibitors that belong to the salicylic acid and quinoline chemotypes. We present their synthesis, biochemical and cellular activities, structure-activity relationships, and provide X-ray structures of several representative FPPS complexes. These novel allosteric FPPS inhibitors are devoid of any affinity for bone mineral and could serve as leads to evaluate their potential in none-bone diseases. PMID- 26381452 TI - A comparison of the quality of fresh and frozen pork from immunologically castrated males versus gilts, physical castrates, and entire males. AB - The objective of this study was to compare pork quality and sensory characteristics of pork from gilts, physical castrates, entire males, and immunological castrates. Loins (Longissimus thoracis et lumborum) were collected at harvest, aged for 10 days, and subsequently cut into chops and roasts. Two chops and one roast were frozen for a minimum of 14 days to a maximum of 30 days and chops and roasts from the same loin were evaluated in fresh form. A trained sensory panel evaluated the samples and results showed that gilt pork, physical castrate pork, and immunological castrate pork were similar in terms of boar odor and pork flavor. The evaluated pork quality characteristics showed no differences among sexes except for marbling in the frozen samples (P<0.05). Results suggest that pork from immunologically castrated males is similar to pork from physical castrates in terms of sensory and pork quality characteristics and between fresh and frozen products. PMID- 26381453 TI - Acid stress mediated adaptive divergence in ion channel function during embryogenesis in Rana arvalis. AB - Ion channels and pumps are responsible for ion flux in cells, and are key mechanisms mediating cellular function. Many environmental stressors, such as salinity and acidification, are known to severely disrupt ionic balance of organisms thereby challenging fitness of natural populations. Although ion channels can have several vital functions during early life-stages (e.g. embryogenesis), it is currently not known i) how developing embryos maintain proper intracellular conditions when exposed to environmental stress and ii) to what extent environmental stress can drive intra-specific divergence in ion channels. Here we studied the moor frog, Rana arvalis, from three divergent populations to investigate the role of different ion channels and pumps for embryonic survival under acid stress (pH 4 vs 7.5) and whether populations adapted to contrasting acidities differ in the relative role of different ion channel/pumps. We found that ion channels that mediate Ca(2+) influx are essential for embryonic survival under acidic pH, and, intriguingly, that populations differ in calcium channel function. Our results suggest that adaptive divergence in embryonic acid stress tolerance of amphibians may in part be mediated by Ca(2+) balance. We suggest that ion flux may mediate adaptive divergence of natural populations at early life-stages in the face of environmental stress. PMID- 26381454 TI - Dynamical backaction cooling with free electrons. AB - The ability to cool single ions, atomic ensembles, and more recently macroscopic degrees of freedom down to the quantum ground state has generated considerable progress and perspectives in fundamental and technological science. These major advances have been essentially obtained by coupling mechanical motion to a resonant electromagnetic degree of freedom in what is generally known as laser cooling. Here, we experimentally demonstrate the first self-induced coherent cooling mechanism that is not mediated by an electromagnetic resonance. Using a focused electron beam, we report a 50-fold reduction of the motional temperature of a nanowire. Our result primarily relies on the sub-nanometre confinement of the electron beam and generalizes to any delayed and spatially confined interaction, with important consequences for near-field microscopy and fundamental nanoscale dissipation mechanisms. PMID- 26381455 TI - To Lecture or Not to Lecture? That is the Question. AB - A quasi-experimental mixed-methods study compared the effects of an unfolding case study with lecture in a nursing orientation class on new graduate registered nurses' knowledge, perceived learning, and satisfaction with the instructional method. Although results showed that the unfolding case study was engaging, learners who received content in a lecture format achieved significantly higher posttest scores. Nursing professional development specialists will find this article helpful when considering instructional methods for new graduate registered nurses. PMID- 26381457 TI - A field experiment with elevated atmospheric CO2-mediated changes to C4 crop herbivore interactions. AB - The effects of elevated CO2 (E-CO2) on maize and Asian corn borer (ACB), Ostrinia furnacalis, in open-top chambers were studied. The plants were infested with ACB and exposed to ambient and elevated (550 and 750 MUl/l) CO2. E-CO2 increased the plant height and kernel number per ear. The plants had lower nitrogen contents and higher TNC: N ratios under E-CO2 than at ambient CO2. The response of plant height to E-CO2 was significantly dampened in plants with ACB infestation. However, the weight gain of the survivors declined in plants grown under E-CO2. Moreover, the plant damage caused by ACB was not different among the treatments. Overwintering larvae developed under E-CO2 had a lower supercooling point than those developed under ambient CO2. The results indicated that there was a positive effect of E-CO2 on the accumulation of maize biomass, i.e., the "air fertilizer" effect, which led to a nutritional deficiency in the plants. The fitness-related parameters of ACB were adversely affected by the CO2-mediated decreased in plant nutritional quality, and ACB might alter its food consumption to compensate for these changes. Larval damage to maize under E-CO2 appears to be offset by this "air-fertilizer" effect, with reductions in larval fitness. PMID- 26381458 TI - Dynamic interface tension of a smectic liquid crystal in anionic surfactant solutions. AB - The interface tension of a smectic liquid crystal with respect to a surrounding ionic surfactant solution is investigated at concentrations above and below the critical micelle concentration (cmc). A simple measurement technique has been developed recently [Phys. Chem. Chem. Phys., 2013, 15, 7204], based on the geometrical analysis of the shape of smectic bubbles in water that are deformed by the buoyancy of trapped air bubbles. After preparation of the smectic membranes in the solution, we measure both the time dependence of their dynamic interface tension as well as the asymptotically reached static tension values. These are established about 15 minutes after the membrane preparation. At large enough concentrations of the surfactant (above the critical micelle concentration), the interface tension drops to 6 mN m(-1). At the lowest possible surfactant concentrations in our experiment, the equilibrium tension reaches 20 mN m(-1), which is almost equal to the smectic surface tension respective to air. The tension of a freshly drawn film exceeds this value by far. PMID- 26381456 TI - Positive regulation of the Shewanella oneidensis OmpS38, a major porin facilitating anaerobic respiration, by Crp and Fur. AB - Major porins are among the most abundant proteins embedded in the outer membrane (OM) of Gram-negative bacteria, playing crucial roles in maintenance of membrane structural integrity and OM permeability. Although many OM proteins (especially c type cytochromes) in Shewanella oneidensis, a research model for respiratory versatility, have been extensively studied, physiological significance of major porins remains largely unexplored. In this study, we show that OmpS38 and OmpA are two major porins, neither of which is responsive to changes in osmolarity or contributes to the intrinsic resistance to beta-lactam antibiotics. However, OmpS38 but not OmpA is largely involved in respiration of non-oxygen electron acceptors. We then provide evidence that expression of ompS38 is transcribed from two promoters, the major of which is favored under anaerobic conditions while the other appears constitutive. The major promoter is under the direct control of Crp, the master regulator dictating respiration. As a result, the increase in the level of OmpS38 correlates with an elevated activity in Crp under anaerobic conditions. In addition, we show that the activity of the major promoter is also affected by Fur, presumably indirectly, the transcription factor for iron dependent gene expression. PMID- 26381459 TI - Pleiotropic drug-resistance attenuated genomic library improves elucidation of drug mechanisms. AB - Identifying Saccharomyces cerevisiae genome-wide gene deletion mutants that confer hypersensitivity to a xenobiotic aids the elucidation of its mechanism of action (MoA). However, the biological activities of many xenobiotics are masked by the pleiotropic drug resistance (PDR) network which effluxes xenobiotics that are PDR substrates. The PDR network in S. cerevisiae is almost entirely under the control of two functionally homologous transcription factors Pdr1p and Pdr3p. Herein we report the construction of a PDR-attenuated haploid non-essential DMA (PA-DMA), lacking PDR1 and PDR3, which permits the MoA elucidation of xenobiotics that are PDR substrates at low concentrations. The functionality of four key cellular processes commonly activated in response to xenobiotic stress: oxidative stress response, general stress response, unfolded stress response and calcium signalling pathways were assessed in the absence of PDR1 and PDR3 genes and were found to unaltered, therefore, these key chemogenomic signatures are not lost when using the PA-DMA. Efficacy of the PA-DMA was demonstrated using cycloheximide and latrunculin A at low nanomolar concentrations to attain chemical genetic profiles that were more specific to their known main mechanisms. We also found a two-fold increase in the number of compounds that are bioactive in the pdr1Deltapdr3Delta compared to the wild type strain in screening the commercially available LOPAC(1280) library. The PA-DMA should be particularly applicable to mechanism determination of xenobiotics that have limited availability, such as natural products. PMID- 26381460 TI - Risk of skin cancer development in 672 patients affected by actinic keratosis. AB - BACKGROUND: Actinic keratoses (AKs) are the most common type of keratinocytic lesions worldwide. The skin areas affected by the so-called "field cancerization" harbor mutagenetic risks for the development of squamous cell carcinoma (SCC). METHODS: We retrospectively investigated the histopathological reports and clinical charts of 672 patients affected by multiple AKs, presenting at least 5 years of follow-up. The frequency of non-melanoma skin cancers (NMSC, namely SCC and basal cell carcinoma [BCC]) and malignant melanomas (MMs) in patients affected by multiple AKs were analyzed. RESULTS: More than 40% of patients with a previous diagnosis of multiple AKs developed an NMSC (SCC or BCC), or an MM, during a follow-up period of 5 to 11 years. The risk of developing another skin malignancy appeared to be higher in the age range between 61 and 80 years. The relative risk of developing a BCC and/or an MM in patients with a previous AK diagnosis was found to be 4.52. CONCLUSIONS: The presence of multiple AKs and "field cancerization" seems to be associated with a high risk not only of NMSC such as SCC and BCC, but also of MM. An adequate follow-up is required in these groups of patients. PMID- 26381461 TI - The facial grid analysis for filler injection: a cohort study of 300 patients. AB - BACKGROUND: Filler injection is widely used for facial rejuvenation. Global skin rejuvenation requires the precise sequential injections of different areas, but a standardized and reproducible method is lacking. The purpose of the study was to develop a new method for a precise measurement of the degree of facial defect before and after full-face rejuvenation with injectable fillers, so called facial filler (FAFI) grid. METHODS: Three hundreds patients were included. There were 76 males and 224 females with a median age of 30.5 years. A grid of horizontal and vertical lines was drawn on the patients' face with a rigid meter and a surgical pen to identify some precise areas for sequential filler injections. The grid was also used to measure the defects and the corrections obtained. Three different formulations of hyaluronic acid were used for treating specific facial areas. RESULTS: Correction was judged adequate in 77% and 90% of cases by the physician and patients, respectively. Prevalence of adverse events was 8.8%, with mostly mild, with resolution in few weeks. CONCLUSIONS: FAFI grid proved to be helpful in guiding sequential injections for total facial rejuvenation. PMID- 26381462 TI - Preparation of Supercapacitors on Flexible Substrates with Electrodeposited PEDOT/Graphene Composites. AB - Composite films consisting of poly(3,4-ethylenedioxythiophene) (PEDOT) and graphene oxide (GO) were electrochemically polymerized by electrooxidation of EDOT in ionic liquid (BMIMBF4) onto flexible electrode substrates. Two polymerization approaches were compared, and the cyclic voltammetry (CV) method was found to be superior to potentiostatic polymerization for the growth of PEDOT/GO films. After deposition, incorporated GO was reduced to rGO by a rapid electrochemical method of repetitive cathodic potential cycling, without using any reducing reagents. The films were characterized in 3-electrode configuration in BMIMBF4. Symmetric supercapacitors with aqueous electrolyte were assembled from the composite films and characterized through cyclic voltammetry and galvanostatic discharge tests. It was shown that PEDOT/rGO composites have better capacitive properties than pure PEDOT or the unreduced composite film. The cycling stability of the supercapacitors was also tested, and the results indicate that the specific capacitance still retains well over 90% of the initial value after 2000 consecutive charging/discharging cycles. The supercapacitors were demonstrated as energy storages in a room light energy harvester with a printed organic solar cell and printed electrochromic display. The results are promising for the development of energy-autonomous, low-power, and disposable electronics. PMID- 26381463 TI - A few key residues determine the high redox potential shift in azurin mutants. AB - The wide range of variability of the reduction potential (E(0)) of blue-copper proteins has been the subject of a large number of studies in the past several years. In particular, a series of azurin mutants have been recently rationally designed tuning E(0) over a very broad range (700 mV) without significantly altering the redox-active site [Marshall et al., Nature, 2009, 462, 113]. This clearly suggests that interactions outside the primary coordination sphere are relevant to determine E(0) in cupredoxins. However, the molecular determinants of the redox potential variability are still undisclosed. Here, by means of atomistic molecular dynamics simulations and hybrid quantum/classical calculations, the mechanisms that determine the E(0) shift of two azurin mutants with high potential shifts are unravelled. The reduction potentials of native azurin and of the mutants are calculated obtaining results in good agreement with the experiments. The analysis of the simulations reveals that only a small number of residues (including non-mutated ones) are relevant in determining the experimentally observed E(0) variation via site-specific, but diverse, mechanisms. These findings open the path to the rational design of new azurin mutants with different E(0). PMID- 26381464 TI - Negishi Approach to 1,5-Disubstituted 3-Amino-1H-1,2,4-triazoles. AB - An efficient synthesis of 1,5-disubstituted 3-amino-1H-1,2,4-triazoles has been achieved via a Negishi coupling of aryl or vinyl bromides and 1-substituted 3 amino-1H-1,2,4-triazoles in the presence of Knochel's base tetramethylpiperidinylzinc chloride lithium chloride (TMPZnCl.LiCl) and catalytic bis(di-tert-butylphenylphosphine)palladium chloride. This chemistry tolerates a variety of electronically diverse aryl or vinyl bromides and 1-substituted 3 amino-1H-1,2,4-triazoles. PMID- 26381465 TI - Strong ferromagnetic exchange interactions in hinge-like Dy(O2Cu)2 complexes involving double oxygen bridges. AB - Two trinuclear isomeric compounds, [{(Cu(II)(salpn))(Me(CO)Me)}2Dy(III)(NO3)3] (1) and [{Cu(II)(salpn)}2Dy(III)(H2O)(NO3)3].MeOH (2), along with one polymeric compound, {[{Cu(II)(salpn)}2Dy(III)(NO3)3bpy].MeOH.H2O}n (3), were synthesized using a metalloligand, [Cu(II)(salpn)], where H2salpn and bpy stand for N,N' bis(salicylidene)-1,3-propanediamine and 4,4'-bipyridine, respectively. Compounds 1 and 2 were selectively prepared with two solvents: the less polar acetone led to the exclusive crystallization of 1 with a transoid trinuclear architecture, while more polar solvent methanol provided sole construction of 2 with a cisoid trinuclear architecture. Compound 3 was prepared from 1 or 2 after bpy was introduced as a bridge. The Dy and Cu ions are doubly bridged with oxygen atoms, and the core DyO2Cu skeletons are characterized by different "butterfly angles" of 140.9(1) degrees , 147.1(19) degrees , and 142.4(2) degrees for 1, 2, and 3, respectively. We have examined the molecular structures and magnetic properties of 1-3 using high-frequency electron paramagnetic resonance (HF-EPR), magnetization, and magnetic susceptibility techniques. These compounds showed slow magnetization reversal in the measurements of alternating current magnetic susceptibility. We analyzed EPR frequency-field diagrams using an effective spin Hamiltonian including only one doublet of Dy sublevels and found that the exchange couplings are ferromagnetic in all compounds. The exchange coupling parameters JDy-Cu of 1, 2, and 3 were determined as 2.25 +/- 0.05, 1.82 +/- 0.04, and 1.79 +/- 0.04 K, respectively. These values are larger than those found in previous research using EPR analysis on [Cu(II)(L(A))(C3H6O)Dy(III)(NO3)3] (H2L(A) = N,N'-bis(3-methoxysalicylidene)-1,3-diamino-2,2-dimethylpropane) and [Dy(III)L(B)2(NO3)2{Cu(II)(CH3OH)}2](NO3)(CH3OH) (H2L(B) = 2,6 bis(acetylaceto)pyridine). The present result shows an advantage of doubly oxygen bridged motifs to built strong ferromagnetic interactions between lanthanide and transition metal ions. We found that the exchange coupling strength is sensitive to the structural parameters such as bond angles, bond lengths, and butterfly angles. Precise determination of the exchange parameters would contribute to development of exchange-coupled 4f-3d heterometallic complexes. PMID- 26381466 TI - Heterogeneous Oxidation of Atmospheric Organic Aerosol: Kinetics of Changes to the Amount and Oxidation State of Particle-Phase Organic Carbon. AB - Atmospheric oxidation reactions are known to affect the chemical composition of organic aerosol (OA) particles over timescales of several days, but the details of such oxidative aging reactions are poorly understood. In this study we examine the rates and products of a key class of aging reaction, the heterogeneous oxidation of particle-phase organic species by the gas-phase hydroxyl radical (OH). We compile and reanalyze a number of previous studies from our laboratories involving the oxidation of single-component organic particles. All kinetic and product data are described on a common basis, enabling a straightforward comparison among different chemical systems and experimental conditions. Oxidation chemistry is described in terms of changes to key ensemble properties of the OA, rather than to its detailed molecular composition, focusing on two quantities in particular, the amount and the oxidation state of the particle phase carbon. Heterogeneous oxidation increases the oxidation state of particulate carbon, with the rate of increase determined by the detailed chemical mechanism. At the same time, the amount of particle-phase carbon decreases with oxidation, due to fragmentation (C-C scission) reactions that form small, volatile products that escape to the gas phase. In contrast to the oxidation state increase, the rate of carbon loss is nearly uniform among most systems studied. Extrapolation of these results to atmospheric conditions indicates that heterogeneous oxidation can have a substantial effect on the amount and composition of atmospheric OA over timescales of several days, a prediction that is broadly in line with available measurements of OA evolution over such long timescales. In particular, 3-13% of particle-phase carbon is lost to the gas phase after one week of heterogeneous oxidation. Our results indicate that oxidative aging represents an important sink for particulate organic carbon, and more generally that fragmentation reactions play a major role in the lifecycle of atmospheric OA. PMID- 26381467 TI - Stretchable Array of Highly Sensitive Pressure Sensors Consisting of Polyaniline Nanofibers and Au-Coated Polydimethylsiloxane Micropillars. AB - We report on the facile fabrication of a stretchable array of highly sensitive pressure sensors. The proposed pressure sensor consists of the top layer of Au deposited polydimethylsiloxane (PDMS) micropillars and the bottom layer of conductive polyaniline nanofibers on a polyethylene terephthalate substrate. The sensors are operated by the changes in contact resistance between Au-coated micropillars and polyaniline according to the varying pressure. The fabricated pressure sensor exhibits a sensitivity of 2.0 kPa(-1) in the pressure range below 0.22 kPa, a low detection limit of 15 Pa, a fast response time of 50 ms, and high stability over 10000 cycles of pressure loading/unloading with a low operating voltage of 1.0 V. The sensor is also capable of noninvasively detecting human pulse waveforms from carotid and radial artery. A 5 * 5 array of the pressure sensors on the deformable substrate, which consists of PDMS islands for sensors and the mixed thin film of PDMS and Ecoflex with embedded liquid metal interconnections, shows stable sensing of pressure under biaxial stretching by 15%. The strain distribution obtained by the finite element method confirms that the maximum strain applied to the pressure sensor in the strain-suppressed region is less than 0.04% under a 15% biaxial strain of the unit module. This work demonstrates the potential application of our proposed stretchable pressure sensor array for wearable and artificial electronic skin devices. PMID- 26381469 TI - Work-Related Eye Injuries. PMID- 26381468 TI - Corneal Collagen Cross-linking: A Review of Clinical Applications. AB - Corneal collagen cross-linking (CXL) has been shown to slow down or stop the progression of keratoconus. In addition, CXL has been applied in cases of corneal ectasia. Recent reports of the use of CXL in cases of infectious keratitis have generated further interest in this treatment modality. This review discusses the principle, clinical uses, and complications associated with CXL. PMID- 26381472 TI - Sex and Employment-Setting Differences in Work-Family Conflict in Athletic Training. AB - CONTEXT: Work-family conflict (WFC) has received much attention in athletic training, yet several factors related to this phenomenon have not been examined, specifically a practitioner's sex, occupational setting, willingness to leave the profession, and willingness to use work-leave benefits. OBJECTIVE: To examine how sex and occupational differences in athletic training affect WFC and to examine willingness to leave the profession and use work-leave benefits. DESIGN: Cross sectional study. SETTING: Multiple occupational settings, including clinic/outreach, education, collegiate, industrial, professional sports, secondary school, and sales. PATIENTS OR OTHER PARTICIPANTS: A total of 246 athletic trainers (ATs) (men = 110, women = 136) participated. Of these, 61.4% (n = 151) were between 20 and 39 years old. MAIN OUTCOME MEASURES(S): Participants responded to a previously validated and reliable WFC instrument. We created and validated a 3-item instrument that assessed willingness to use work-leave benefits, which demonstrated good internal consistency (Cronbach alpha = 0.88), as well as a single question about willingness to leave the profession. RESULTS: The mean (+/- SD) WFC score was 16.88 +/- 4.4 (range = 5 [least amount of conflict] to 25 [highest amount of conflict]). Men scored 17.01 +/- 4.5, and women scored 16.76 +/- 4.36, indicating above-average WFC. We observed no difference between men and women based on conflict scores (t244 = 0.492, P = .95) or their willingness to leave the profession (t244 = -1.27, P = .21). We noted differences among ATs in different practice settings (F8,245 = 5.015, P <.001); those in collegiate and secondary school settings had higher reported WFC scores. A negative relationship existed between WFC score and comfort using work-leave benefits (2-tailed r = -0.533, P < .001). Comfort with using work-leave benefits was different among practice settings (F8,245 = 3.01, P = .003). CONCLUSIONS: The ATs employed in traditional practice settings reported higher levels of WFC. Male and female ATs had comparable experiences of WFC and willingness to leave the profession. PMID- 26381474 TI - Verbal Description of Concrete Objects: A Method for Assessing Semantic Circumlocution in Persons With Aphasia. AB - PURPOSE: We investigated from a theoretically motivated perspective what information differentiated sufficient from insufficient descriptions of objects provided by persons with aphasia. METHOD: Twenty-one adults with aphasia consequent to single left-hemisphere stroke verbally described 9 living and 9 nonliving objects. Responses were scored for accuracy (i.e., sufficiency) and tallied for type and quantity of semantic feature information provided. Main effects and interactions were identified using repeated measures analyses of variance, with significant findings followed up with planned comparisons. RESULTS: Differences between correct and incorrect descriptions were identified with respect to both feature type and feature distinctiveness for living and nonliving items, in particular highlighting the importance of distinctive features in descriptions of both domains. CONCLUSIONS: These findings add to the relatively small body of literature investigating semantic feature processing in adults with aphasia. This is a critical gap to close when considered in light of the preponderance of semantically based treatments for word-retrieval impairment in stroke-aphasia. Our findings provide preliminary support for the notion that semantically guided treatments for word-retrieval impairment in stroke-aphasia may be geared toward increasing specificity of semantic circumlocution to increase semantic self-cueing and to improve communication of information to conversation partners. PMID- 26381475 TI - Does the presence of autoantibodies without autoimmune diseases and hereditary thrombophilia have an effect on recurrent pregnancy loss? AB - OBJECTIVE: To assess whether the presence of autoantibodies has any effect on recurrent pregnancy loss (RPL) and obstetric complications in women who do not have autoimmune diseases and hereditary thrombophilia. METHODS: Retrospectively, 515 patients who underwent antibody investigation with anti-nuclear antibody, extractable nuclear antigen, anti-double stranded DNA, anti-parietal cell, anti smooth muscle, anti-mitochondrial (AMA), anti-thyroid peroxidase, anti thyroglobulin (anti-TG) and anti-phospholipid (aPL) at Hacettepe University were included. Of those patients, 212 had one or more autoantibodies whereas the remaining 303 were negative for all autoantibodies. RPL was the primary outcome and was defined as >=2 pregnancy losses (n = 119). RESULTS: The frequency of RPL was significantly higher in the autoantibody positive group than controls (28.3% versus 14.5%, p<0.001). Anti-TG (21.2% versus 7.8%, p < 0.001), aPL (18.3% versus 5.6%, p < 0.001) and AMA (4.8% versus 0.5%, p = 0.001) antibodies were more common in patients with RPL. For the view of obstetric complications, oligohydramniosis (3.8% versus 0.7%, p = 0.03) and stillbirth (17.0% versus 10.6%, p = 0.002) were significantly higher in the autoantibody-positive group. CONCLUSIONS: Even in women without autoimmune disease or hereditary thrombophilia, autoantibodies per se might directly increase the risk of RPL and obstetric complications. The screening anti-TG and aPL autoantibodies in the first step might be considered in patients with RPL. PMID- 26381473 TI - National Athletic Trainers' Association Position Statement: Exertional Heat Illnesses. AB - OBJECTIVE: To present best-practice recommendations for the prevention, recognition, and treatment of exertional heat illnesses (EHIs) and to describe the relevant physiology of thermoregulation. BACKGROUND: Certified athletic trainers recognize and treat athletes with EHIs, often in high-risk environments. Although the proper recognition and successful treatment strategies are well documented, EHIs continue to plague athletes, and exertional heat stroke remains one of the leading causes of sudden death during sport. The recommendations presented in this document provide athletic trainers and allied health providers with an integrated scientific and clinically applicable approach to the prevention, recognition, treatment of, and return-to-activity guidelines for EHIs. These recommendations are given so that proper recognition and treatment can be accomplished in order to maximize the safety and performance of athletes. RECOMMENDATIONS: Athletic trainers and other allied health care professionals should use these recommendations to establish onsite emergency action plans for their venues and athletes. The primary goal of athlete safety is addressed through the appropriate prevention strategies, proper recognition tactics, and effective treatment plans for EHIs. Athletic trainers and other allied health care professionals must be properly educated and prepared to respond in an expedient manner to alleviate symptoms and minimize the morbidity and mortality associated with these illnesses. PMID- 26381476 TI - Multifunctional copolymer coating of polyethylene glycol, glycidyl methacrylate, and REDV to enhance the selectivity of endothelial cells. AB - Multifunctional polymer coatings have potential applications in biomaterials. These coatings possess reactive functional groups for the immobilization of specific biological factors that can influence cellular behavior. These coatings also display low nonspecific protein adsorption. In this study, we prepared a multifunctional polymer coating through the deposition of random copolymers of poly(ethylene glycol) methacrylate (PEGMA) and glycidyl methacrylate (GMA) to prevent nonspecific attachment and enable the covalence of Arg-Glu-Asp-Val (REDV) peptide with endothelial cells (ECs) selectivity. Coatings were characterized by X-ray photoelectron spectroscopy (XPS). The adhesion and proliferation of ECs and smooth muscle cells (SMCs) onto the REDV-modified surface were investigated to understand the synergistic action of antifouling PEG and EC selective REDV peptide conjugated GMA. The copolymers containing GMA and PEG groups are very useful as a multifunctional coating material with anti-fouling and ECs specific adhesion for implant materials surface modification. PMID- 26381477 TI - How can novel microscopic approaches shed light on the function of nucleic acid based drugs? PMID- 26381478 TI - Wheat-dependent exercise-induced anaphylaxis. AB - Wheat-dependent exercise-induced anaphylaxis (WDEIA) is a rare, but potentially severe food allergy exclusively occurring when wheat ingestion is accompanied by augmenting cofactors. It is clinically characterized by anaphylactic reactions ranging from urticaria and angioedema to dyspnoea, hypotension, collapse, and shock. WDEIA usually develops after ingestion of wheat products followed by physical exercise. Other cofactors are acetylsalicylic acid and other non steroidal anti-inflammatory drugs, alcohol, and infections. The precise mechanisms of WDEIA remain unclear; exercise and other cofactors might increase gastrointestinal allergen permeability and osmolality, redistribute blood flow, or lower the threshold for IgE-mediated mast cell degranulation. Among wheat proteins, omega5-gliadin and high-molecular-weight glutenin subunits have been reported to be the major allergens. In some patients, WDEIA has been discussed to be caused by epicutaneous sensitization with hydrolysed wheat gluten included in cosmetics. Diagnosis is made based on the patient's history in combination with allergy skin testing, determination of wheat-specific IgE serum antibodies, basophil activation test, histamine release test, and/or exercise challenge test. Acute treatment includes application of adrenaline or antihistamines. The most reliable prophylaxis of WDEIA is a gluten-free diet. In less severe cases, a strict limitation of wheat ingestion before exercise and avoidance of other cofactors may be sufficient. PMID- 26381479 TI - Investigating the prevalence of Salmonella in dogs within the Midlands region of the United Kingdom. AB - BACKGROUND: The intimate relationship between dogs and their owners has the potential to increase the risk of human exposure to bacterial pathogens. Over the past 40 years, there have been several reports on transmission of salmonellae from dogs to humans. This study therefore aimed to determine the prevalence of Salmonella in the faeces of dogs from the Midlands region of the United Kingdom to assess exposure risk and potential for zoonotic transmission. RESULTS: A total of 436 apparently healthy dogs without diarrhoea from households (n = 126), rescue centres (n = 96), boarding kennels (n = 43), retired greyhound kennels (n = 39) and a pet nutrition facility (n = 132) were investigated for Salmonella shedding. Faecal samples were processed by an enrichment culture based method. The faeces from one dog (0.23 %; 95 % confidence limit 0.006 %, 1.27 %) was positive for Salmonella. The species was S. enterica subspecies arizonae. CONCLUSION: This study showed that the prevalence of Salmonella from faeces from apparently healthy dogs from a variety of housing conditions is low; however, Salmonella shedding was still identified. PMID- 26381480 TI - Physico-chemical and microbiological characterisation of Italian fermented sausages in relation to their size. AB - BACKGROUND: The aim of this work was to study the physico-chemical and microbiological parameters of 10 Italian fermented sausages, produced industrially, in order to highlight the differences in relation to their size. The sausages were classified as small, medium and large and the data concerning every feature considered were analysed with some statistical explorative tools: ANOVA, principal component analysis (PCA) and linear discriminant analysis (LDA). RESULTS: Significant differences in relation to the sausage size were found regarding microbial populations (in particular, enterobacteria and staphylococci). The pH was higher in the small sausages, and consequently the presence of lactate and acetate was higher in the bigger one. Also the biogenic amine content (particularly tyramine, cadaverine and putrescine) was influenced by the size. CONCLUSIONS: In spite of the extreme variability of the sausage types at the end of ripening, this work showed that it was possible to find a strict relationship between sausages diameter and some essential physico-chemical parameters. Thus, the cross-sectional size of the product is an essential parameter, which can drive the biochemical processes during ripening, not only by affecting the kinetics of water losses, but also by influencing the microbiota enzymatic activity. (c) 2015 Society of Chemical Industry. PMID- 26381481 TI - Causes of adult female deaths in Bangladesh: findings from two National Surveys. AB - BACKGROUND: Assessment of causes of death and changes in pattern of causes of death over time are needed for programmatic purposes. Limited national level data exist on the adult female causes of death in Bangladesh. METHOD: Using data from two nationally representation surveys, the 2001 and 2010 Bangladesh Maternal Mortality Surveys (BMMS), the paper examines the causes of adult female death, aged 15-49 years, and changes in the patterns of these deaths. In both surveys, all household deaths three years prior to the survey were identified. Adult female deaths were then followed by a verbal autopsy (VA) using the WHO structured questionnaire. Two physicians independently reviewed the VA forms to assign a cause of death using the ICD-10; in case of disagreement, a third physician made an independent review and assigned a cause of death. RESULTS: The overall mortality rates for women aged 15-49 in 2001 and 2010 were 182 per 100,000 and 120 per 100,000 respectively. There is a shift in the pattern of causes of death during the period covered by the two surveys. In the 2001 survey, the main causes of death were maternal (20 %), followed by diseases of the circulatory system (15 %), malignancy (14 %) and infectious diseases (13 %). However, in the 2010 survey, malignancies were the leading cause (21 %), followed by diseases of the circulatory system (16 %), maternal causes (14 %) and infectious diseases (8 %). While maternal deaths remained the number one cause of death among 20-34 years old in both surveys, unnatural deaths were the main cause for teenage deaths, and malignancies were the main cause of death for older women. Although there is an increasing trend in the proportion of women who died in hospitals, in both surveys most women died at home (74 % in 2001 and 62 % in 2010). CONCLUSION: The shift in the pattern of causes of adult female deaths is in agreement with the overall change in the disease pattern from communicable to non-communicable diseases in Bangladesh. Suicide and other violent deaths as the primary cause of deaths among teenage girls demands specific interventions to prevent such premature deaths. Prevention of deaths due to non-communicable diseases should also be a priority. PMID- 26381482 TI - Leaves of grass: focusing phenomics on maize leaf growth. AB - The detailed analysis of leaf growth dynamics, when coupled with transcriptomic research, can facilitate the discovery of genes required for leaf elongation.Please see related Research article: http://www.genomebiology.com/2015/16/1/168. PMID- 26381483 TI - Elevated free fatty acid level is a risk factor for early postoperative hypoxemia after on-pump coronary artery bypass grafting: association with endothelial activation. AB - BACKGROUND: We aimed to investigate the relationship between increased free fatty acid (FFA) level and early postoperative hypoxemia after coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB). METHODS: Ninety-eight consecutive patients undergoing CABG were enrolled. Early postoperative hypoxemia was defined as the lowest of the ratio of arterial oxygen tension (PaO2) to inspired oxygen fraction (FiO2) <= 200 mm Hg within 24 h without pleural effusion and pneumothorax. The 26 perioperative factors, serum levels of FFA and inflammatory cytokines between the hypoxemia and non-hypoxemia groups were recorded or detected using autoanalyzer and enzyme-linked immunosorbent assay, respectively. Additionally, the risk factors for early postoperative hypoxemia were evaluated using multiple logistic regression analysis. RESULTS: The incidence rate of early postoperative hypoxemia was 37.8 %. Serum FFA levels were significantly higher in the hypoxemia group than in the non-hypoxemia group (P<0.001). Further, postoperative serum FFA levels were inversely related to the lowest of the ratio of PaO2/FiO2 at 24 h after CABG (r= - 0.367, P<0.001). Multiple logistic regression analysis confirmed that age, body mass index and postoperative serum FFA concentrations were independently associated with early postoperative hypoxemia. Notably, patients with hypoxemia had markedly higher serum intercellular adhesion molecule-1 (ICAM-1) levels than those without (P<0.001). Moreover, serum FFA levels at 2 h after CABG correlated positively with ICAM-1 concentrations (r=0.492, P<0.001). CONCLUSIONS: Elevated FFA concentration is a risk factor for early postoperative hypoxemia after on-pump CABG, which may be closely associated with endothelial activation. PMID- 26381484 TI - Management of Lateral Elbow Tendinopathy: One Size Does Not Fit All. AB - Synopsis Clear guidelines for the clinical management of individuals with lateral elbow tendinopathy (LET) are hampered by many proposed interventions and the condition's prognosis, ranging from immediate resolution of symptoms following simple advice in some patients to long-lasting problems, regardless of treatment, in others. This is compounded by our lack of understanding of the complexity of the underlying pathophysiology of LET. In this article, we collate evidence and expert opinion on the pathophysiology, clinical presentation, and differential diagnosis of LET. Factors that might provide prognostic value or direction for physical rehabilitation, such as the presence of neck pain, tendon tears, or central sensitization, are canvassed. Clinical recommendations for physical rehabilitation are provided, including the prescription of exercise and adjunctive physical therapy and pharmacotherapy. A preliminary algorithm, including targeted interventions, for the management of subgroups of patients with LET based on identified prognostic factors is proposed. Further research is needed to evaluate whether such an approach may lead to improved outcomes and more efficient resource allocation. J Orthop Sports Phys Ther 2015;45(11):938 949. Epub 17 Sep 2015. doi:10.2519/jospt.2015.5841. PMID- 26381485 TI - Association Between Anatomical Characteristics, Knee Laxity, Muscle Strength, and Peak Knee Valgus During Vertical Drop-Jump Landings. AB - STUDY DESIGN: Controlled laboratory study; cross-sectional. OBJECTIVES: To investigate the relationship among anatomical variables, knee laxity, muscle strength, and peak knee valgus angles during a vertical drop-jump landing task. BACKGROUND: Excessive knee valgus has been associated with anterior cruciate ligament injury in females; however, the influence of anatomical characteristics, knee laxity, and muscle strength on frontal plane knee motion is not completely understood. METHODS: Norwegian elite female soccer players (n = 279; mean +/- SD age, 21 +/- 4 years; height, 167 +/- 6 cm; body mass, 63 +/- 7 kg) were evaluated from 2009 through 2012. The evaluation included 3-D motion analysis of a vertical drop jump, anatomical measures (height, static knee valgus, leg length, and static foot posture), knee laxity, and muscle strength (quadriceps, hamstrings, and hip abductors). Multiple linear regression analyses were used to investigate the relationships among anatomical characteristics, knee laxity, muscle strength, and peak knee valgus angles. RESULTS: Anatomical characteristics explained 11% of the variance in peak knee valgus angles (P<.001), with height and static knee valgus being significant predictors. CONCLUSION: Greater body height and static knee valgus were associated with greater peak knee valgus angles during a vertical drop-jump landing task. However, these variables only explained 11% of the variance in peak knee valgus. PMID- 26381486 TI - Gluteal Tendinopathy: Integrating Pathomechanics and Clinical Features in Its Management. AB - Synopsis Gluteal tendinopathy is now believed to be the primary local source of lateral hip pain, or greater trochanteric pain syndrome, previously referred to as trochanteric bursitis. This condition is prevalent, particularly among postmenopausal women, and has a considerable negative influence on quality of life. Improved prognosis and outcomes in the future for those with gluteal tendinopathy will be underpinned by advances in diagnostic testing, a clearer understanding of risk factors and comorbidities, and evidence-based management programs. High-quality studies that meet these requirements are still lacking. This clinical commentary provides direction to assist the clinician with assessment and management of the patient with gluteal tendinopathy, based on currently limited available evidence on this condition and the wider tendon literature and on the combined clinical experience of the authors. J Orthop Sports Phys Ther 2015;45(11):910-922. Epub 17 Sep 2015. doi:10.2519/jospt.2015.5829. PMID- 26381487 TI - A novel experimental model of Cryptococcus neoformans-related immune reconstitution inflammatory syndrome (IRIS) provides insights into pathogenesis. AB - Antiretroviral therapy (ART) has yielded major advances in fighting the HIV pandemic by restoring protective immunity. However, a significant proportion of HIV patients co-infected with the opportunistic fungal pathogen Cryptococcus neoformans paradoxically develops a life-threatening immune reconstitution inflammatory syndrome (IRIS) during antiretroviral therapy. Despite several clinical studies, the underlying pathomecha-nisms are poorly understood. Here, we present the first mouse model of cryptococcal IRIS that allows for a detailed analysis of disease development. Lymphocyte-deficient RAG-1(-/-) mice are infected with C. neoformans and 4 weeks later adoptively transferred with purified CD4(+) T cells. Reconstitution of CD4(+) T cells is sufficient to induce a severe inflammatory disease similar to clinical IRIS in C. neoformans-infected RAG-1(-/-) mice of different genetic backgrounds and immunological phenotypes (i.e. C57BL/6 and BALB/c). Multiorgan inflammation is accompanied by a systemic release of distinct proinflammatory cytokines, i.e. IFN-gamma, IL-6, and TNF alpha. IRIS development is characterized by infection-dependent activation of donor CD4(+) T cells, which are the source of IFN-gamma. Interestingly, IFN-gamma mediated effects are not required for disease induction. Taken together, this novel mouse model of cryptococcal IRIS provides a useful tool to verify potential mechanisms of pathogenesis, revealing targets for diagnosis and therapeutic interventions. PMID- 26381488 TI - Reliability and validity of three questionnaires measuring context-specific sedentary behaviour and associated correlates in adolescents, adults and older adults. AB - BACKGROUND: Reliable and valid measures of total sedentary time, context-specific sedentary behaviour (SB) and its potential correlates are useful for the development of future interventions. The purpose was to examine test-retest reliability and criterion validity of three newly developed questionnaires on total sedentary time, context-specific SB and its potential correlates in adolescents, adults and older adults. METHODS: Reliability and validity was tested in six different samples of Flemish (Belgium) residents. For the reliability study, 20 adolescents, 22 adults and 20 older adults filled out the age-specific SB questionnaire twice. Test-retest reliability was analysed using Kappa coefficients, Intraclass Correlation Coefficients and/or percentage agreement, separately for the three age groups. For the validity study, data were retrieved from 62 adolescents, 33 adults and 33 older adults, with activPALTM as criterion measure. Spearman correlations and Bland-Altman plots (or non parametric approach) were used to analyse criterion validity, separately for the three age groups and for weekday, weekend day and average day. RESULTS: The test retest reliability for self-reported total sedentary time indicated following values: ICC = 0.37-0.67 in adolescents; ICC = 0.73-0.77 in adults; ICC = 0.68 0.80 in older adults. Item-specific reliability results (e.g. context-specific SB and its potential correlates) showed good-to-excellent reliability in 67.94%, 68.90% and 66.38% of the items in adolescents, adults and older adults respectively. All items belonging to sedentary-related equipment and simultaneous SB showed good reliability. The sections of the questionnaire with lowest reliability were: context-specific SB (adolescents), potential correlates of computer use (adults) and potential correlates of motorized transport (older adults). Spearman correlations between self-reported total sedentary time and the activPALTM were different for each age group: rho = 0.02-0.42 (adolescents), rho = 0.06-0.52 (adults), rho = 0.38-0.50 (older adults). Participants over-reported total sedentary time (except for weekend day in older adults) compared to the activPALTM, for weekday, weekend day and average day respectively by +57.05%, +46.29%, +53.34% in adolescents; +40.40%, +19.15%, +32.89% in adults; +10.10%, 6.24%, +4.11% in older adults. CONCLUSIONS: The questionnaires showed acceptable test-retest reliability and criterion validity. However, over-reporting of total SB was noticeable in adolescents and adults. Nevertheless, these questionnaires will be useful in getting context-specific information on SB. PMID- 26381490 TI - A how-to approach for estimation of surface/Stern potentials considering ionic size and polarization. AB - Electrostatic potential in the electric double layer is an important parameter that significantly affects a large number of physical, chemical and biological properties and processes. In the present study, a new approach for the estimation of surface potential and Stern potential considering ionic volume and polarization was developed. Ionic strong polarization in the diffuse layer increases its effective charge and determines the Stern potential, while ionic volume in the Stern layer strongly decreases its effective charge and determines the surface potential. For example, the effective charge of K(+) is increased by 0.699 (from 1 to 1.699) resulting from polarization, while it is decreased by 1.359 (from 1.699 to 0.240) due to finite size. The determined surface potential is about 7 times as high as the Stern potential. The effects of volume and polarization on the surface/Stern potentials were quantified respectively, and the former was stronger than the latter. A new theory was verified by the experiments for aggregates stability. The present work also showed that only introduction of the strong polarization into the DLVO theory can describe the interactions of colloidal particles. PMID- 26381489 TI - Vaccination of boys or catch-up of girls above 11 years of age with the HPV-16/18 AS04-adjuvanted vaccine: where is the greatest benefit for cervical cancer prevention in Italy? AB - BACKGROUND: Since 2007, a Human Papillomavirus (HPV) vaccination programme against cervical cancer (CC) is implemented in Italy in 11-year-old girls. The extension of HPV vaccination to young adult women, or to 11-year-old boys could further reduce the CC burden, in the latter case from indirect effect on HPV transmission. The objective of the study was to compare the potential CC cases prevention from HPV-16/18 AS04-adjuvanted vaccination of adding catch-up targeting 15- or 25-year-old girls to the addition of boys vaccination in Italy. The models assessing the impact of these alternative vaccination strategies are usually dynamic models requiring numerous input data. Simpler models could however provide some insight into this question, as reported in the current study. METHODS: A published cohort model adapted to the Italian setting was used to estimate the potential CC reduction following different HPV vaccination strategies with a HPV-16/18 AS04-adjuvanted vaccine: vaccination of 11-year-old girls, female aged 15 or 25 years. The model assumed that the maximum benefit obtained from vaccinating boys equals the CC reduction that would result from immunisation of all non-vaccinated girls of the same age. Each cohort of 11-year olds (either girls or boys) was assumed to include 281,000 individuals and a 70% vaccination coverage was applied. Sensitivity analysis was performed by varying the vaccination coverage and the overlap in potential sexual contacts between vaccinated boys and girls of the same age-group. RESULTS: Under base case, compared with the screening-only scenario, HPV vaccination of 11-year-old girls, 15-year-old females, 25-year-old females or 11-year-old boys, would prevent 1,146, 1,082, 788 or 491 CC cases respectively. HPV vaccination of boys could result in more CC cases prevented than adding a female catch-up only in scenarios with low vaccination coverage in the primary target cohort and when combined with small overlap between vaccinated boys and girls of the same age cohort. CONCLUSIONS: For a fixed limited additional budget allowing the inclusion of a single catch-up cohort, the extension of HPV vaccination to girls or young women instead of boys was estimated to maximise the number of CC cases prevented. PMID- 26381491 TI - Xenotransplantation and porcine cytomegalovirus. AB - Porcine microorganisms may be transmitted to the human recipient when xenotransplantation with pig cells, tissues, and organs will be performed. Most of such microorganisms can be eliminated from the donor pig by specified or designated pathogen-free production of the animals. As human cytomegalovirus causes severe transplant rejection in allotransplantation, considerable concern is warranted on the potential pathogenicity of porcine cytomegalovirus (PCMV) in the setting of xenotransplantation. On the other hand, despite having a similar name, PCMV is different from HCMV. The impact of PCMV infection on pigs is known; however, the influence of PCMV on the human transplant recipient is unclear. However, first transplantations of pig organs infected with PCMV into non-human primates were associated with a significant reduction of the survival time of the transplants. Sensitive detection methods and strategies for elimination of PCMV from donor herds are required. PMID- 26381492 TI - Justifying clinical trials for porcine islet xenotransplantation. AB - The development of the Edmonton Protocol encouraged a great deal of optimism that a cell-based cure for type I diabetes could be achieved. However, donor organ shortages prevent islet transplantation from being a widespread solution as the supply cannot possibly equal the demand. Porcine islet xenotransplantation has the potential to address these shortages, and recent preclinical and clinical trials show promising scientific support. Consequently, it is important to consider whether the current science meets the ethical requirements for moving toward clinical trials. Despite the potential risks and the scientific unknowns that remain to be investigated, there is optimism regarding the xenotransplantation of some types of tissue, and enough evidence has been gathered to ethically justify clinical trials for the most safe and advanced area of research, porcine islet transplantation. Researchers must make a concerted effort to maintain a positive image for xenotransplantation, as a few well publicized failed trials could irrevocably damage public perception of xenotransplantation. Because all of society carries the burden of risk, it is important that the public be involved in the decision to proceed. As new information from preclinical and clinical trials develops, policy decisions should be frequently updated. If at any point evidence shows that islet xenotransplantation is unsafe, then clinical trials will no longer be justified and they should be halted. However, as of now, the expected benefit of an unlimited supply of islets, combined with adequate informed consent, justifies clinical trials for islet xenotransplantation. PMID- 26381493 TI - Impact of donor age and weaning status on pancreatic exocrine and endocrine tissue maturation in pigs. AB - BACKGROUND: During the process of islet isolation, pancreatic enzymes are activated and released, adversely affecting islet survival and function. We hypothesize that the exocrine component of pancreases harvested from pre-weaned juvenile pigs is immature and hence pancreatic tissue from these donors is protected from injury during isolation and prolonged tissue culture. METHODS: Biopsy specimens taken from pancreases harvested from neonatal (5-10 days), pre weaned juvenile (18-22 days), weaned juvenile (45-60 days), and young adult pigs (>90 days) were fixed and stained with hematoxylin and eosin. Sections were examined under a fluorescent microscope to evaluate exocrine zymogen fluorescence intensity (ZFI) and under an electron microscope to evaluate exocrine zymogen granule density (ZGD). RESULTS: Exocrine content estimation showed significantly lower ZFI and ZGD in juvenile pig pancreases (1.5 +/- 0.04 U/MUm(2) , ZFI; 1.03 +/- 0.07 * 10(3) /100 MUm(2) , ZGD) compared to young adult pigs (2.4 +/- 0.05U/MUm(2) , ZFI; 1.53 +/- 0.08 * 10(3) /100 MUm(2) ZGD). Islets in juvenile pig pancreases were on average smaller (105.2 +/- 11.2 MUm) than islets in young adult pigs (192 +/- 7.7 MUm), but their insulin content was comparable (80.9 +/- 2.2% juvenile; 84.2 +/- 0.3% young adult, P > 0.05). All data expressed as mean +/- SEM. CONCLUSION: Porcine islet xenotransplantation continues to make strides toward utilization in clinical trials of type 1 diabetes. Porcine donor age and weaning status influence the extent of exocrine maturation of the pancreas. Juvenile porcine pancreases may represent an alternative donor source for islet xenotransplantation as their exocrine component is relatively immature; this preserves islet viability during extended tissue culture following isolation. PMID- 26381494 TI - Inclusion of homologous DNA in nuclease-mediated gene targeting facilitates a higher incidence of bi-allelically modified cells. AB - BACKGROUND: Recent advancements in gene editing techniques have increased in number and utility. These techniques are an attractive alternative to conventional gene targeting methods via homologous recombination due to the ease of use and the high efficiency of gene editing. We have previously produced cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH) knockout (KO) pigs in a Minnesota miniature pig genetic background. These pigs were generated using zinc-finger nucleases (ZFNs) in combination with donor DNA containing a total homology length of 1600 bp (800-bp homology on each arm). Our next aim was to introduce the targeted disruption of alpha-1,3-galactosyltransferase (GGTA1) in the CMAH KO genetic background and evaluate the effect of donor DNA homology length on meganuclease-mediated gene targeting. METHODS: Zinc-finger nucleases from a previous CMAH KO experiment were used as a proof of concept to identify a correlation between the length of donor DNA homology and targeting efficiency. Based on those results, experiments were designed to use transcription activator like effector nucleases (TALENs) to generate bi-allelically modified GGTA1 cells using donor DNAs carrying various lengths of homology. Donor DNA was designed to symmetrically flank the predicted cleavage sites in CMAH and GGTA1 for both ZFN and TALEN cleavage sites, respectively. For both genes, the length of total homology ranged from 60 to 1799 bp. Sialyltransferase gene expression profiles were evaluated in CMAH and GGTA1 double KO pig cells and were compared to wild type and CMAH KO cells. RESULTS: Introduction of donor DNA with ZFNs demonstrated that small amounts of homology (60 bp) could facilitate homology-directed repair during ZFN-mediated targeting of CMAH; however, donor DNA with longer amounts of homology resulted in a higher frequency of homology-directed repair. For the GGTA1 KO experiments that used TALENs and donor DNA, donor DNA alone did not result in detectable bi-allelic conversion of GGTA1. As the length of donor DNA increased, the bi-allelic disruption of GGTA1 increased from 0.5% (TALENs alone, no donor DNA present) to a maximum of 3% (TALENs and donor DNA with total homology of 1799 bp). Inclusion of homologous donor DNA in TALEN-mediated gene targeting facilitated a higher incidence of bi-allelically modified cells. Using the generated cells, we were able to demonstrate the lack of GGTA1 expression and the decrease in gene expression sialyltransferase-related genes. CONCLUSIONS: The approach of using donor DNA in conjunction with a meganuclease can be used to increase the efficiency of gene targeting. The gene editing methods can be applied to other genes as well as other mammalian systems. Additionally, gene expression analysis further confirms that the CMAH/GGTA1 double KO pigs can be a valuable source for the study of pig-to-human xenotransplantation. PMID- 26381496 TI - Updating threshold-based identification of hospitalists in 2012 Medicare pay data. AB - In the absence of a unique identifier, it is difficult to assess the number of practicing hospitalists. We use a variety of thresholds of billing activity to identify hospitalists in a dataset of publicly released 2012 Medicare physician pay data. Our study updates previous estimates of the number of hospitalists practicing nationwide in 2012 and suggests the field continues to grow. This research also highlights a need for a more precise system of identifying hospitalists. PMID- 26381495 TI - Beneficial effect of a nitric oxide donor in an ex vivo model of pig-to-human pulmonary xenotransplantation. AB - BACKGROUND: Nitric oxide (NO) can reduce platelet adhesion and vascular resistance. Tempol can scavenge the reactive oxygen species (ROS) that induce tissue injury. As xenograft rejection attenuates endogenous NO production and generates ROS, we evaluated the potential effect of an NO donor (SIN-1, 3 morpholinosydnonimine) and tempol on hyperacute xenograft dysfunction using an ex vivo porcine lung perfusion model. METHODS: For the evaluation of von Willebrand factor (vWF) secretion, human endothelial cells were stimulated with thrombin. Porcine lungs were perfused with either fresh human whole blood (unmodified control group [n = 4]), SIN-1 (n = 4), or SIN and tempol (n = 4). RESULTS: SIN-1 and tempol significantly inhibited vWF secretion from endothelial cells in vitro. However, they did not suppress xenogeneic complement activation. In an ex vivo pulmonary perfusion model, SIN-1 improved pulmonary xenograft function by reducing pulmonary vascular resistance (PVR), inhibiting complement activation, and inhibiting thrombin generation. Combined treatment with tempol and SIN-1 potentiated PVR reduction, but slightly enhanced complement activation. CONCLUSIONS: An NO donor is expected to improve pulmonary xenograft function through inhibition of vWF secretion, vasoconstriction, thrombin generation, and indirectly through inhibition of complement activation. The additional effects of tempol on an NO donor were not considered significant in an ex vivo xenograft system. PMID- 26381497 TI - Late prematurity and adiposity in adolescents: Evidence from "Children of 1997" birth cohort. AB - OBJECTIVE: The association of late prematurity with later adiposity is unclear, and the mediating role of infant growth is seldom studied. We assessed the association of late prematurity with markers of adiposity in adolescence and tested whether accelerated infant weight gain mediated the association. METHODS: In the Chinese birth cohort "Children of 1997," we used multivariable linear regression to assess the adjusted association of late premature (n = 295), compared to term (n = 6874), births with markers of adiposity at 14 years. We tested whether any association was mediated by accelerated weight gain from birth to 12 months, i.e., a change in weight z-score >=0.67. RESULTS: Late premature births had greater body mass index (BMI) z-score (0.21, 95% confidence interval (CI) 0.07, 0.35), waist-hip ratio z-score (0.16, 95% CI 0.03, 0.29), and waist height ratio z-score (0.27, 95% CI 0.14, 0.40) than term births in adolescence. The association of late prematurity with higher adolescent BMI, but not waist ratios, was mediated by accelerated infant weight gain. CONCLUSIONS: Late prematurity was associated with higher BMI and waist ratios in adolescence, but only the association with BMI was mediated by infant weight gain, suggesting vulnerability to metabolic risk in late premature births may arise through multiple pathways. PMID- 26381499 TI - Effect of Dimethyl Sulfoxide and Melatonin on the Isolation of Human Primary Hepatocytes. AB - The availability of fully functional human hepatocytes is critical for progress in human hepatocyte transplantation and the development of bioartificial livers and in vitro liver systems. However, the cell isolation process impairs the hepatocyte status and determines the number of viable cells that can be obtained. This study aimed to evaluate the effects of using dimethyl sulfoxide (DMSO) and melatonin in the human hepatocyte isolation protocol. Human hepatocytes were isolated from liver pieces resected from 10 patients undergoing partial hepatectomy. Each piece was dissected into 2 equally sized pieces and randomized, in 5 of 10 isolations, to perfusion with 1% DMSO-containing perfusion buffer or buffer also containing 5 mM melatonin using the 2-step collagenase perfusion technique (experiment 1), and in the other 5 isolations to standard perfusion or perfusion including 1% DMSO (experiment 2). Tissues perfused with DMSO yielded 70.6% more viable hepatocytes per gram of tissue (p = 0.076), with a 26.1% greater albumin production (p < 0.05) than those perfused with control buffer. Melatonin did not significantly affect (p > 0.05) any of the studied parameters, but cell viability, dehydrogenase activity, albumin production, urea secretion, and 7-ethoxycoumarin O-deethylase activity were slightly higher in cells isolated with melatonin-containing perfusion buffer compared to those isolated with DMSO. In conclusion, addition of 1% DMSO to the hepatocyte isolation protocol could improve the availability and functionality of hepatocytes for transplantation, but further studies are needed to clarify the mechanisms involved. PMID- 26381500 TI - Risk for girls can be adversely affected post-term due to underestimation of gestational age by ultrasound in the second trimester. AB - INTRODUCTION: Post-term pregnancies are associated with greater risks for mother and child. Accurate determination of gestational age is necessary for safe care. Female fetuses have been shown to be smaller than males at the time of second trimester ultrasound (US) examination, leading to underestimation of their age and, potentially, greater impacts of perinatal complications in post-term girls than in post-term boys. The purpose of this study was to investigate the sex ratio of post-term births and differences in perinatal complications (stillbirth, low Apgar score, low birthweight, meconium aspiration and low umbilical artery pH) between post-term boys and girls according to dating method [second-trimester US and last menstrual period (LMP)]. MATERIAL AND METHODS: Data from gestational week >=39 to delivery of 13 338 singleton pregnancies between 13 February 2006 and 15 January 2014, were collected from the Obstetrix((r)) (Siemens Healthcare) medical records system in Dalarna County, Sweden. RESULTS: The neonatal male:female ratio increased with gestational age after week 40, as dated by US, reaching 1.69 in gestational week 42. This ratio remained 1 throughout gestation according to dating by the LMP. Post-term pregnancy increased the risks of meconium aspiration and low Apgar score, with no sex difference observed. CONCLUSIONS: US gestational dating indicated that more boys than girls were born post-term, whereas dating according to LMP revealed no sex difference. These results support the hypothesis that female fetuses are smaller than males, leading to underestimation of their gestational age, at the time of second trimester US examination. PMID- 26381498 TI - Polymorphism in drug resistance genes dihydrofolate reductase and dihydropteroate synthase in Plasmodium falciparum in some states of India. AB - BACKGROUND: Sulfadoxine-pyrimethamine (SP) combination drug is currently being used in India for the treatment of Plasmodium falciparum as partner drug in artemisinin-based combination therapy (ACT). Resistance to sulfadoxine and pyrimethamine in P. falciparum is linked with mutations in dihydropteroate synthase (pfdhps) and dihydrofolate reductase (pfdhfr) genes respectively. This study was undertaken to estimate the prevalence of such mutations in pfdhfr and pfdhps genes in four states of India. METHODS: Plasmodium falciparum isolates were collected from two states of India with high malaria incidence i.e., Jharkhand and Odisha and two states with low malaria incidence i.e., Andhra Pradesh and Uttar Pradesh between years 2006 to 2012. Part of sulfadoxine pyrimethamine (SP) drug resistance genes, pfdhfr and pfdhps were PCR-amplified, sequenced and analyzed. RESULTS: A total of 217 confirmed P. falciparum isolates were sequenced for both Pfdhfr and pfdhps gene. Two pfdhfr mutations 59R and 108N were most common mutations prevalent in all localities in 77 % of isolates. Additionally, I164L was found in Odisha and Jharkhand only (4/70 and 8/84, respectively). Another mutation 51I was found in Odisha only (3/70). The pfdhps mutations 436A, 437G, 540E and 581G were found in Jharkhand and Odisha only in 13, 26, 14 and 13 % isolates respectively, and was absent in Uttar Pradesh and Andhra Pradesh. Combined together for pfdhps and pfdhfr locus, triple, quadruple, quintuple and sextuple mutations were present in Jharkhand and Odisha while absent in Uttar Pradesh and Andhra Pradesh. CONCLUSION: While only double mutants of pfdhfr was present in low transmission area (Uttar Pradesh and Andhra Pradesh) with total absence of pfdhps mutants, up to sextuple mutations were present in high transmission areas (Odisha and Jharkhand) for both the genes combined. Presence of multiple mutations in pfdhfr and pfdhps genes linked to SP resistance in high transmission area may lead to fixation of multiple mutations in presence of high drug pressure and high recombination rate. PMID- 26381501 TI - Should we abandon regional anesthesia in open inguinal hernia repair in adults? AB - Inguinal hernia repair is a common worldwide surgical procedure usually done in the outpatient setting. The purpose of this systematic review is to make an evidence-based meta-analysis to determine the possible benefits of regional (neuraxial block) anesthesia compared to general anesthesia in open inguinal hernia repair in adults. Cochrane Library, Medline, EMBASE, CINAHL, SCI-EXPANDED, SCOPUS as well as trial registries, conference proceedings and reference lists were searched. Only randomized controlled trials (RCT) that compare neuraxial block (spinal or/and epidural) anesthesia (NABA) and general anesthesia (GA) were included. Main outcome measures were postoperative complications, urinary retention and postoperative pain. Seven RCTs were included in this review. A total of 308 patients were analyzed with 154 patients in each group. Overall complications were evenly distributed in NABA and in GA group [OR 1.17, 95 % CI (0.52-2.66)]. Urinary retention was statistically less frequent in GA group compared to NABA group [OR 0.25, 95 % CI (0.08-0.74)]. Movement-associated pain score 24 h after surgery was significantly lower in NABA group [SMD 5.59, 95 % CI (3.69-7.50)]. Time of first analgesia application was shorter in GA group [SMD 8.99, 95 % CI 6.10-11.89]. Compared to GA, NABA appears to be a more adequate technique in terms of postoperative pain control. However, when GA is applied, patients seem to have less voiding problems. PMID- 26381502 TI - Synthesis, characterization and properties of salicylhydrazide salicylacylhydrazone derivatives and their terbium complexes. AB - A series of terbium complexes with salicylhydrazide-salicylacylhydrazone derivatives were synthesized and characterized by elemental analysis, IR spectra, UV/vis spectra and thermal analysis. The luminescence and electrochemical properties of the terbium complexes were investigated. The results show that all the target complexes exhibited characteristic emissions of terbium ions and the complex substituted by the chlorine has the strongest luminescence intensity with the highest quantum yield at 0.609. The introduction of donating electron groups could increase the oxidation potential and the highest occupied molecular orbital energy level of the terbium complex; however, the introduction of accepting electron groups gave the opposite result. PMID- 26381503 TI - How the Target Hemoglobin of Renal Anemia Should Be. AB - Renal anemia is caused by the deficiency of endogenous erythropoietin (Epo) due to renal dysfunction. We think that it is possible to slow the progression of chronic kidney disease (CKD) in case we initiate Epo early in pre-dialysis patients, especially in the non-diabetic population. Erythropoiesis stimulating agent (ESA) treatments targeting mild anemia (10-12 g/dl) can decrease the risk of occurrence of cardiovascular disease (CVD) in patients with hypertension, diabetes mellitus and congestive heart failure. As the large randomized controlled trials such as Cardiovascular Risk Reduction by Early Anemia Treatment with Epoetin Beta, Correction of Hemoglobin and Outcomes in Renal Insufficiency and Trial to Reduce Cardiovascular Events with Aranesp Thearpy in the Western countries suggested, we do not recommend high doses of ESA to achieve the target hemoglobin (Hb) level. The target Hb of >13 g/dl might lead to increase in the risk of CVD although maintaining a high Hb of >12 g/dl without ESA is not harmful for CKD patients. It is desirable to determine the target Hb in dialysis patients depending on their ages. Renal anemia should be monitored constantly to start ESA and iron replacement therapy at an appropriate time, while avoiding their excess in order to minimize the occurrence of CVD and other complications. Taken all the international guidelines and our clinical experiences together, we should consider administration of ESA when the Hb level becomes <11 g/dl in pre-dialysis patients and <10 g/dl in dialysis patients. PMID- 26381504 TI - Downhill Running Excessive Training Inhibits Hypertrophy in Mice Skeletal Muscles with Different Fiber Type Composition. AB - The aim of this study was to verify the effects of running overtraining protocols performed in downhill, uphill, and without inclination on the proteins related to hypertrophy signaling pathway in extensor digitorum longus (EDL) and soleus of C57BL/6 mice. We also performed histological and stereological analyses. Rodents were divided into control (CT; sedentary mice), overtrained by downhill running (OTR/down), overtrained by uphill running (OTR/up), and overtrained by running without inclination (OTR). The incremental load, exhaustive, and grip force tests were used as performance evaluation parameters. 36 h after the grip force test, EDL and soleus were removed and immediately used for immunoblotting analysis or stored at -80 degrees C for histological and stereological analyses. For EDL, OTR/down decreased the protein kinase B (Akt) and tuberous sclerosis protein 2 (TSC2) phosphorylation (p), and increased myostatin, receptor-activated Smads (pSMAD2-3), and insulin receptor substrate-1 (pIRS-1; Ser307/636). OTR/down also presented low and high relative proportions of cytoplasm and connective tissue, respectively. OTR/up increased the mammalian target of rapamycin (pmTOR), 70-kDa ribosomal protein S6 kinase 1 (pS6K1) and pSMAD2-3, and decreased pTSC2. OTR decreased pTSC2 and increased pIRS-1 (Ser636). For soleus, OTR/down increased S6 ribosomal protein (pS6RP) and pSMAD2-3, and decreased pIRS-1 (Ser639). OTR/up decreased pS6K1, pS6RP and pIRS-1 (Ser639), and increased pTSC2 (Ser939), and pSMAD2-3. OTR increased pS6RP, 4E-binding protein-1 (p4E-BP1), pTSC2 (Ser939), and pSMAD2-3, and decreased pIRS-1 (Ser639). In summary, OTR/down inhibited the skeletal muscle hypertrophy with concomitant signs of atrophy in EDL. The effects of OTR/up and OTR depended on the analyzed skeletal muscle type. PMID- 26381505 TI - Birth Weight and Social Trust in Adulthood: Evidence for Early Calibration of Social Cognition. AB - Social trust forms the fundamental basis for social interaction within societies. Understanding the cognitive architecture of trust and the roots of individual differences in trust is of key importance. We predicted that one of the factors calibrating individual levels of trust is the intrauterine flow of nutrients from mother to child as indexed by birth weight. Birth weight forecasts both the future external environment and the internal condition of the individual in multiple ways relevant for social cognition. Specifically, we predicted that low birth weight is utilized as a forecast of a harsh environment, vulnerable condition, or both and, consequently, reduces social trust. The results of the study reported here are consistent with this prediction. Controlling for many confounds through sibling and panel designs, we found that lower birth weight reduced social trust in adulthood. Furthermore, we obtained tentative evidence that this effect is mitigated if adult environments do not induce stress. PMID- 26381507 TI - Iconic Gestures Facilitate Discourse Comprehension in Individuals With Superior Immediate Memory for Body Configurations. AB - To understand a speaker's gestures, people may draw on kinesthetic working memory (KWM)-a system for temporarily remembering body movements. The present study explored whether sensitivity to gesture meaning was related to differences in KWM capacity. KWM was evaluated through sequences of novel movements that participants viewed and reproduced with their own bodies. Gesture sensitivity was assessed through a priming paradigm. Participants judged whether multimodal utterances containing congruent, incongruent, or no gestures were related to subsequent picture probes depicting the referents of those utterances. Individuals with low KWM were primarily inhibited by incongruent speech-gesture primes, whereas those with high KWM showed facilitation-that is, they were able to identify picture probes more quickly when preceded by congruent speech and gestures than by speech alone. Group differences were most apparent for discourse with weakly congruent speech and gestures. Overall, speech-gesture congruency effects were positively correlated with KWM abilities, which may help listeners match spatial properties of gestures to concepts evoked by speech. PMID- 26381506 TI - Conceptual Conditioning: Mechanisms Mediating Conditioning Effects on Pain. AB - Classical conditioning can profoundly modify subsequent pain responses, but the mechanisms that drive this effect are unresolved. In pain-conditioning studies, cues are typically conditioned to primary aversive reinforcers; hence, subsequent pain modulation could reflect learned precognitive associations (i.e., those involving neural plasticity independent of expectations and other forms of conceptual thought) or conceptual expectancies. We isolated conceptual contributions using a thermal pain-conditioning procedure in which different conditioned stimulus (CS) cues were repeatedly paired with symbolic representations of high and low noxious heat. In a subsequent test phase, identical noxious stimuli evoked larger skin conductance responses (SCRs) and pain ratings when preceded by CS cues associated with high temperature than by those associated with low temperature. These effects were mediated by participants' self-reported expectancies. CS cues associated with high temperature also evoked larger anticipatory SCRs than did CS cues associated with low temperature, but larger anticipatory SCRs predicted smaller subsequent heat evoked SCRs. These results provide novel evidence that conditioned modulation of pain physiology can be acquired through purely conceptual processes, and that self-reported expectancies and physiological threat responses have opposing effects on pain. PMID- 26381508 TI - AS-703026 Inhibits LPS-Induced TNFalpha Production through MEK/ERK Dependent and Independent Mechanisms. AB - Chronic obstructive pulmonary disease (COPD) is characterized by intense lung infiltrations of immune cells (macrophages and monocytes). Lipopolysaccharide (LPS) activates macrophages/monocytes, leading to production of tumor necrosis factor alpha (TNFalpha) and other cytokines, which cause subsequent lung damages. In the current study, our results demonstrated that AS-703026, a novel MEK/ERK inhibitor, suppressed LPS-induced TNFalpha mRNA expression and protein secretion in RAW 264.7 murine macrophages, and in murine bone marrow-derived macrophages (BMDMs). Meanwhile, TNFalpha production in LPS-stimulated COPD patents' peripheral blood mononuclear cells (PBMCs) was also repressed by AS-703026. At the molecular level, we showed that AS-703026 blocked LPS-induced MEK/ERK activation in above macrophages/monocytes. However, restoring ERK activation in AS-703026-treated RAW 264.7 cells by introducing a constitutive-actively (CA) ERK1 only partially reinstated LPS-mediated TNFalpha production. Meanwhile, AS 703026 could still inhibit TNFalpha response in ERK1/2-depleted (by shRNA) RAW 264.7 cells. Significantly, we found that AS-703026 inhibited LPS-induced nuclear factor kappaB (NFkappaB) activation in above macrophages and COPD patients' PBMCs. In vivo, oral administration of AS-703026 inhibited LPS-induced TNFalpha production and endotoxin shock in BALB/c mice. Together, we show that AS-703026 in vitro inhibits LPS-induced TNFalpha production in macrophages/monocytes, and in vivo protects mice from LPS-induced endotoxin shock. Thus, it could be further studied as a useful anti-inflammatory therapy for COPD patients. PMID- 26381509 TI - Identification of Intrastent Pathology Associated With Late Stent Thrombosis Using Optical Coherence Tomography. AB - OBJECTIVE: To better characterize intrastent pathology using optical coherence tomography (OCT) in patients presenting with late and very late stent thrombosis (LST/VLST). BACKGROUND: The contribution of specific intrastent pathologies to the development of LST/VLST is not well understood. METHODS: In this single center, retrospective, observational study of 796 consecutive patients treated for ST-segment elevation myocardial infarction (STEMI) with primary PCI we identified 57 patients (7.2%) in whom STEMI resulted from LST/VLST. Of the patients with LST/VLST, 21 patients (37%) had OCT performed at the discretion of the operator during PCI for LST/VLST. Independent reviewers performed qualitative offline analysis of OCT images to determine the cause of stent thrombosis defined as the specific intrastent pathology associated with thrombus deposition. RESULTS: The principal intrastent pathology causing LST/VLST was determined to be stent malapposition in 11 patients (55%), of which 5 (25% of all LST/VLST patents) had findings suggestive of positive vessel remodeling. Neoatherosclerosis was determined to be the cause of LST/VLST in 7 patients (35%). LST/VLST resulted from uncovered stent struts in 2 patients (10%). Among all LST/VLST patients, in-hospital mortality (12.3%) and post-hospital target vessel failure (TVF) or cardiac death (21.7%, median follow-up 1.6 years) remained high. There was a trend towards decreased TVF or cardiac death (7.7% vs. 27.3% P = 0.24) in patients who underwent OCT-guided therapy. CONCLUSIONS: LST/VLST remains a significant cause of STEMI and is associated with considerable morbidity and mortality. OCT use at the time of PCI consistently identifies significant intrastent pathology with potentially meaningful clinical impact. PMID- 26381510 TI - Imaging Surrogates of Disease Activity in Neuromyelitis Optica Allow Distinction from Multiple Sclerosis. AB - Inflammatory demyelinating lesions of the central nervous system are a common feature of both neuromyelitis optica and multiple sclerosis. Despite this similarity, it is evident clinically that the accumulation of disability in patients with neuromyelitis optica is relapse related and that a progressive phase is very uncommon. This poses the question whether there is any pathological evidence of disease activity or neurodegeneration in neuromyelitis optica between relapses. To investigate this we conducted a longitudinal advanced MRI study of the brain and spinal cord in neuromyelitis optica patients, comparing to patients with multiple sclerosis and controls. We found both cross-sectional and longitudinal evidence of diffusely distributed neurodegenerative surrogates in the multiple sclerosis group (including thalamic atrophy, cervical cord atrophy and progressive widespread diffusion and myelin water imaging abnormalities in the normal appearing white matter) but not in those with neuromyelitis optica, where localised abnormalities in the optic radiations of those with severe visual impairment were noted. In addition, between relapses, there were no new silent brain lesions in the neuromyelitis optica group. These findings indicate that global central nervous system neurodegeneration is not a feature of neuromyelitis optica. The work also questions the theory that neurodegeneration in multiple sclerosis is a chronic sequela to prior inflammatory and demyelinating pathology, as this has not been found to be the case in neuromyelitis optica where the lesions are often more destructive. PMID- 26381511 TI - Bufalin Reverses Resistance to Sorafenib by Inhibiting Akt Activation in Hepatocellular Carcinoma: The Role of Endoplasmic Reticulum Stress. AB - Sorafenib is the standard first-line therapeutic treatment for patients with advanced hepatocellular carcinoma (HCC), but its use is hampered by the development of drug resistance. The activation of Akt by sorafenib is thought to be responsible for this resistance. Bufalin is the major active ingredient of the traditional Chinese medicine Chan su, which inhibits Akt activation; therefore, Chan su is currently used in the clinic to treat cancer. The present study aimed to investigate the ability of bufalin to reverse both inherent and acquired resistance to sorafenib. Bufalin synergized with sorafenib to inhibit tumor cell proliferation and induce apoptosis. This effect was at least partially due to the ability of bufalin to inhibit Akt activation by sorafenib. Moreover, the ability of bufalin to inactivate Akt depended on endoplasmic reticulum (ER) stress mediated by inositol-requiring enzyme 1 (IRE1). Silencing IRE1 with siRNA blocked the bufalin-induced Akt inactivation, but silencing eukaryotic initiation factor 2 (eIF2) or C/EBP-homologous protein (CHOP) did not have the same effect. Additionally, silencing Akt did not influence IRE1, CHOP or phosphorylated eIF2alpha expression. Two sorafenib-resistant HCC cell lines, which were established from human HCC HepG2 and Huh7 cells, were refractory to sorafenib induced growth inhibition but were sensitive to bufalin. Thus, Bufalin reversed acquired resistance to sorafenib by downregulating phosphorylated Akt in an ER stress-dependent manner via the IRE1 pathway. These findings warrant further studies to examine the utility of bufalin alone or in combination with sorafenib as a first- or second-line treatment after sorafenib failure for advanced HCC. PMID- 26381512 TI - Serum Urate and Incident Cardiovascular Disease: The Coronary Artery Risk Development in Young Adults (CARDIA) Study. AB - OBJECTIVE: There is controversy about whether serum urate (sUA) predicts future cardiovascular disease (CVD) independently of classical risk factors, and the age at which any prediction starts. We studied the sUA-CVD association among generally healthy adults. METHODS: CARDIA recruited 5115 black and white individuals aged 18-30 years in 1985-1986 (year-0). Fatal and nonfatal CVD events by year 27 (n = 164) were ascertained during annual contacts and classified using medical records. The association with sUA (year-0, 10, 15 and 20) was modeled using Cox proportional hazards regression, pooling over gender-specific quartiles. RESULTS: Mean sUA concentration was higher in men than women, but increased over time in both genders. Those with elevated sUA had worse metabolic profiles that substantially deteriorated over time. Adjusting for demographic and lifestyle factors (the minimal model), baseline sUA concentration was positively associated with incident CVD (hazard ratio (HR) per mg/dL = 1.21; 95% confidence interval: 1.05, 1.39; P = 0.005). This positive association attenuated to nonsignificance in the full model accounting simultaneously for classical CVD risk factors (HR = 1.09; 0.94, 1.27; P = 0.24). Both the minimal and full models appeared to show stronger associations (than year-0 sUA) between year-10 sUA and incident CVD (HR = 1.27 and 1.12, respectively), but sUA was not statistically significant in the full model. Despite fewer events, year-15 sUA showed a significant sUA-CVD association pattern, with minimal model association magnitude comparable to year-10, and remained significant in the full model (HR = 1.19; 1.02, 1.40; P = 0.03). Hyperuricemia at year-15 strongly predicted CVD risk (HR = 2.11; 1.34, 3.33; P = 0.001), with some attenuation in the full model (HR = 1.68; P = 0.04). CONCLUSIONS: sUA may be an early biomarker for CVD in adults entering middle age. The prediction of CVD by sUA appeared to strengthen with aging. The potential complex relation of sUA with deterioration of a cluster of metabolic abnormalities warrants future exploration. PMID- 26381513 TI - Serine 363 of a Hydrophobic Region of Archaeal Ribulose 1,5-Bisphosphate Carboxylase/Oxygenase from Archaeoglobus fulgidus and Thermococcus kodakaraensis Affects CO2/O2 Substrate Specificity and Oxygen Sensitivity. AB - Archaeal ribulose 1, 5-bisphospate carboxylase/oxygenase (RubisCO) is differentiated from other RubisCO enzymes and is classified as a form III enzyme, as opposed to the form I and form II RubisCOs typical of chemoautotrophic bacteria and prokaryotic and eukaryotic phototrophs. The form III enzyme from archaea is particularly interesting as several of these proteins exhibit unusual and reversible sensitivity to molecular oxygen, including the enzyme from Archaeoglobus fulgidus. Previous studies with A. fulgidus RbcL2 had shown the importance of Met-295 in oxygen sensitivity and pointed towards the potential significance of another residue (Ser-363) found in a hydrophobic pocket that is conserved in all RubisCO proteins. In the current study, further structure/function studies have been performed focusing on Ser-363 of A. fulgidus RbcL2; various changes in this and other residues of the hydrophobic pocket point to and definitively establish the importance of Ser-363 with respect to interactions with oxygen. In addition, previous findings had indicated discrepant CO2/O2 specificity determinations of the Thermococcus kodakaraensis RubisCO, a close homolog of A. fulgidus RbcL2. It is shown here that the T. kodakaraensis enzyme exhibits a similar substrate specificity as the A. fulgidus enzyme and is also oxygen sensitive, with equivalent residues involved in oxygen interactions. PMID- 26381514 TI - Efficacy and safety of World Health Organization group 5 drugs for multidrug resistant tuberculosis treatment. AB - The efficacy and toxicity of several drugs now used to treat multidrug-resistant tuberculosis (MDR-TB) have not been fully evaluated. We searched three databases for studies assessing efficacy in MDR-TB or safety during prolonged treatment of any mycobacterial infections, of drugs classified by the World Health Organization as having uncertain efficacy for MDR-TB (group 5). We included 83 out of 4002 studies identified. Evidence was inadequate for meropenem, imipenem and terizidone. For MDR-TB treatment, clarithromycin had no efficacy in two studies (risk difference (RD) -0.13, 95% CI -0.40-0.14) and amoxicillin clavulanate had no efficacy in two other studies (RD 0.07, 95% CI -0.21-0.35). The largest number of studies described prolonged use for treatment of non tuberculous mycobacteria. Azithromycin was not associated with excess serious adverse events (SAEs). Clarithromycin was not associated with excess SAEs in eight controlled trials in HIV-infected patients (RD 0.00, 95% CI -0.02-0.02), nor in six uncontrolled studies in HIV-uninfected patients, whereas six uncontrolled studies in HIV-infected patients clarithromycin caused substantial SAEs (proportion 0.20, 95% CI 0.12-0.27). For most group 5 drugs we found inadequate evidence of safety for prolonged use or for efficacy for MDR-TB, although macrolides appeared to be safe in prolonged use. PMID- 26381516 TI - How does a new breathlessness support service affect patients? PMID- 26381515 TI - Erlotinib versus carboplatin and paclitaxel in advanced lepidic adenocarcinoma: IFCT-0504. AB - The IFCT-0504 phase II trial evaluated the efficacy of erlotinib versus carboplatin-paclitaxel (CP) as first-line treatment in 130 cases of advanced lepidic-predominant adenocarcinoma (ADC).The primary objective of the study was treatment efficacy, evaluated based on an end-point of disease control at 16 weeks.The primary objective was met, with a disease control in 35 (53%) out of 66 patients treated with CP and in 25 (39.1%) out of 64 patients treated with erlotinib. Median progression-free survival (PFS) for the total population was 3.6 months. The disease control rate did not differ between either the therapeutic arms or pathological subtypes, whereas there was a strong interaction between treatment arms and tumour pathological subtypes for PFS (p=0.009). Mucinous tumour patients treated with erlotinib exhibited an increased progression risk (hazard ratio 3.4, 95% CI 1.7-6.5; p<=0.001). The PFS for nonmucinous tumour patients was similar in both arms. Median overall survival was 20.1 months and did not differ between therapeutic arms. These findings were not further elucidated by molecular analyses and the toxicity profiles were as expected.Our study demonstrated the dominant role of CP alongside erlotinib in the management of advanced lepidic ADC. Based on these findings, erlotinib should not be administered in first-line therapy to patients with lepidic ADC in the absence of an epidermal growth factor receptor mutation. PMID- 26381517 TI - Restrictive chronic lung function decline after haematopoietic stem cell transplantation. PMID- 26381518 TI - Continuous fat-free mass decline in COPD: fact or fiction? PMID- 26381519 TI - Activated protein C inhibits neutrophil migration in allergic asthma: a randomised trial. AB - Asthma patients show evidence of a procoagulant state in their airways, accompanied by an impaired function of the anticoagulant protein C system. We aimed to study the effect of recombinant human activated protein C (rhAPC) in allergic asthma patients.We conducted a randomised, double-blind, placebo controlled, proof-of-concept study in house dust mite (HDM) allergic asthma patients. Patients were randomised to receive intravenous rhAPC (24 ug.kg(-1).h( 1); n=12) or placebo (n=12) for 11 h. 4 h after the start of infusion, a first bronchoscopy was performed to challenge one lung segment with saline (control) and a contralateral segment with a combination of HDM extract and lipopolysaccharide (HDM+LPS), thereby mimicking environmental house dust exposure. A second bronchoscopy was conducted 8 h after intrabronchial challenge to obtain bronchoalveolar lavage fluid (BALF).rhAPC did not influence HDM+LPS induced procoagulant changes in the lung. In contrast, rhAPC reduced BALF leukocyte counts by 43% relative to placebo, caused by an inhibitory effect on neutrophil influx (64% reduction), while leaving eosinophil influx unaltered. rhAPC also reduced neutrophil degranulation products in the airways.Intravenous rhAPC attenuates HDM+LPS-induced neutrophil migration and protein release in allergic asthma patients by an effect that does not rely on coagulation inhibition. PMID- 26381520 TI - Phenotyping chronic pulmonary aspergillosis by cluster analysis. PMID- 26381521 TI - Progressive ventilation inhomogeneity in infants with cystic fibrosis after pulmonary infection. AB - Measures of ventilation distribution are promising for monitoring early lung disease in cystic fibrosis (CF). This study describes the cross-sectional and longitudinal impacts of pulmonary inflammation and infection on ventilation homogeneity in infants with CF.Infants diagnosed with CF underwent multiple breath washout (MBW) testing and bronchoalveolar lavage at three time points during the first 2 years of life.Measures were obtained for 108 infants on 156 occasions. Infants with a significant pulmonary infection at the time of MBW showed increases in lung clearance index (LCI) of 0.400 units (95% CI 0.150 0.648; p=0.002). The impact was long lasting, with previous pulmonary infection leading to increased ventilation inhomogeneity over time compared to those who remained free of infection (p<0.05). Infection with Haemophilus influenzae was particularly detrimental to the longitudinal lung function in young children with CF where LCI was increased by 1.069 units for each year of life (95% CI 0.484 1.612; p<0.001).Pulmonary infection during the first year of life is detrimental to later lung function. Therefore, strategies aimed at prevention, surveillance and eradication of pulmonary pathogens are paramount to preserve lung function in infants with CF. PMID- 26381523 TI - Superconductivity and disorder effect in TlNi2Se(2-x)S(x) compounds. AB - After our first discovery of multi-band superconductivity (SC) in the TlNi2Se2 crystal, we successfully grew a series of TlNi2Se(2-x)S(x) (0.0 <= x <= 2.0) single crystals. Measurements of resistivity, specific heat, and susceptibility were carried out on these crystals. Superconductivity with T(C) = 2.3 K was first observed in the TlNi2S2 crystal, which also appears to involve heavy electrons with an effective mass m* = 13-25 m(b), as inferred from the normal state electronic specific heat and the upper critical field, H(C2)(T). It was found that bulk SC and heavy-electron behavior is preserved in all the studied TlNi2Se(2-x)S(x) samples. In the mixed state, a novel change of the field dependence of the residual specific heat coefficient, gamma(N)(H), occurs in TlNi2Se(2-x)S(x) with increasing S content. We also found that the T(C) value changes with the disorder degree induced by the partial substitution of S for Se, characterized by the residual resistivity ratio (RRR). Thus, the TlNi2Se(2-x)S(x) system provides a platform to study the effect of disorder on the multi-band SC. PMID- 26381522 TI - Impact of Lymph Node Ratio on Oncologic Outcomes in ypStage III Rectal Cancer Patients Treated with Neoadjuvant Chemoradiotherapy followed by Total Mesorectal Excision, and Postoperative Adjuvant Chemotherapy. AB - PURPOSE: To evaluate the prognostic impact of the lymph node ratio (LNR) in ypStage III rectal cancer patients who were treated with neoadjuvant chemoradiotherapy (NCRT). MATERIALS AND METHODS: We retrospectively reviewed the data of 638 consecutive patients who underwent NCRT followed by total mesorectal excision, and postoperative adjuvant chemotherapy for rectal cancer from 2004 to 2011. Of these, 125 patients were positive for lymph node (LN) metastasis and were analyzed in this study. RESULTS: The median numbers of examined and metastatic LNs were 17 and 2, respectively, and the median LNR was 0.143 (range, 0.02-1). Median follow-up time was 55 months. In multivariate analyses, LNR was an independent prognostic factor for overall survival (OS) (hazard ratio [HR] 2.17, p = 0.041), disease-free survival (DFS) (HR 2.28, p = 0.005), and distant metastasis-free survival (DMFS) (HR 2.30, p = 0.010). When ypN1 patients were divided into low (low LNR ypN1 group) and high LNR (high LNR ypN1 group) according to a cut-off value of 0.152, the high LNR ypN1 group had poorer OS (p = 0.043) and DFS (p = 0.056) compared with the low LNR ypN1 group. And there were no differences between the high LNR ypN1 group and the ypN2 group in terms of the OS (p = 0.703) and DFS (p = 0.831). CONCLUSIONS: For ypN-positive rectal cancer patients, the LNR was a more effective prognostic marker than the ypN stage, circumferential resection margin, or tumor regression grade after NCRT, and could be used to discern the high-risk group among ypN1 patients. PMID- 26381524 TI - The Influence of Single Nucleotide Polymorphism Microarray-Based Molecular Karyotype on Preimplantation Embryonic Development Potential. AB - In order to investigate the influence of the molecular karyotype based on single nucleotide polymorphism (SNP) microarray on embryonic development potential in preimplantation genetic diagnosis (PGD), we retrospectively analyzed the clinical data generated by PGD using embryos retrieved from parents with chromosome rearrangements in our center. In total, 929 embryos from 119 couples had exact diagnosis and development status. The blastocyst formation rate of balanced molecular karyotype embryos was 56.6% (276/488), which was significantly higher than that of genetic imbalanced embryos 24.5% (108/441) (P<0.001). No significant difference was detected in blastocyst formation rates in the groups of maternal age <30, 30-35 and >35 respectively. Blastocyst formation rates of male and female embryos were 44.5% (183/411) and 38.8% (201/518) respectively, with no significant difference between them (P>0.05). The rates of balanced molecular karyotype embryos vary from groups of embryos with different cell numbers at 68 hours after insemination. The blastocyst formation rate of embryos with 6-8 cells (48.1%) was significantly higher than that of embryos with <6 cells (23.9%) and with >8 cells (42.9%) (P<0.05). As for the unbalanced embryos, there was no significant difference of the distribution of abnormal molecular karyotypes in the subgroup of the arrest, morula and blastocyst. Thus, we conclude that embryos with balanced molecular karyotype have significant higher development potential than those with imbalanced molecular karyotype whilst maternal age, embryo gender and types of abnormal molecular karyotype have no significant influence on blastocyst formation. Compared with embryos with <6 and >8 cells, embryos with 6 8 blastomeres have higher rate of balanced molecular karyotype and blastocyst formation. PMID- 26381525 TI - Desynchronization in EEG during perception of means-end actions and relations with infants' grasping skill. AB - The current study examined age-related differences in electroencephalogram (EEG) activity during perception of means-end actions and production of grasps, and how EEG activity may relate to infants' motor competence. We collected data from 9- and 12-month-old infants during perception of means-end actions made with a tool and during execution of their own grasps. We computed event-related desynchronization (ERD) during perception and production events and assessed infants' reach-grasp competence by looking at their latency to complete grasps. Although we found greater ERD during perception of means-end actions in 9-month olds compared with 12-month-olds, we found the relation between ERD during perception and emerging reach-grasp competence to be specific for 12-month-olds and not for 9-month-olds. These results provide evidence for an emerging neural system that supports the coupling of action and perception with infants' emerging motor competence in the first year of life. PMID- 26381526 TI - Implementing Patch Clamp and Live Fluorescence Microscopy to Monitor Functional Properties of Freshly Isolated PKD Epithelium. AB - Cyst initiation and expansion during polycystic kidney disease is a complex process characterized by abnormalities in tubular cell proliferation, luminal fluid accumulation and extracellular matrix formation. Activity of ion channels and intracellular calcium signaling are key physiologic parameters which determine functions of tubular epithelium. We developed a method suitable for real-time observation of ion channels activity with patch-clamp technique and registration of intracellular Ca2+ level in epithelial monolayers freshly isolated from renal cysts. PCK rats, a genetic model of autosomal recessive polycystic kidney disease (ARPKD), were used here for ex vivo analysis of ion channels and calcium flux. Described here is a detailed step-by-step procedure designed to isolate cystic monolayers and non-dilated tubules from PCK or normal Sprague Dawley (SD) rats, and monitor single channel activity and intracellular Ca2+ dynamics. This method does not require enzymatic processing and allows analysis in a native setting of freshly isolated epithelial monolayer. Moreover, this technique is very sensitive to intracellular calcium changes and generates high resolution images for precise measurements. Finally, isolated cystic epithelium can be further used for staining with antibodies or dyes, preparation of primary cultures and purification for various biochemical assays. PMID- 26381527 TI - Neutrophil CD64 is upregulated in RA patients with lymphoma but not in other solid cancers. AB - OBJECTIVE: To evaluate the utility of quantifying CD64 expression on neutrophils in rheumatoid arthritis patients with malignancy, especially its diagnostic role in lymphoma. METHODS: We used flow cytometry to quantify CD64 expression on neutrophils from patients diagnosed with malignancy during the follow-up period prior to initiating treatment. RESULTS: Neutrophils from 18 patients with lymphoma expressed significantly higher levels of CD64 (9635.6 +/- 2123.7 molecules/cell) than those from 32 patients with other solid cancers (carcinoma) (1250.5 +/- 91.1 molecules/cell) (p < 0.001). When the cutoff value was set at 2060 molecules/cell, the sensitivity and specificity of CD64 for diagnosing lymphoma was 88.9% and 94.4%, respectively. CONCLUSIONS: The quantitative measurement of neutrophil CD64 by flow cytometry may be useful as a subsidiary diagnostic marker in patients with suspected lymphoma. Although neutrophil CD64 is currently a well-known marker of infection, it is necessary to bear in mind that lymphoma is also a candidate in differential diagnosis when CD64 expression on neutrophils is upregulated. PMID- 26381528 TI - Examination of Learning Trajectories for Simulated Lumbar Puncture Training Using Hand Motion Analysis. AB - OBJECTIVES: A prospective cohort study was conducted using hand motion analysis (HMA) to assess the acquisition and retention of technical proficiency among first-year medical students learning the lumbar puncture (LP) skill in a simulated setting. METHODS: Twenty-five subjects attended three or four simulation sessions at 6-week intervals. The initial session consisted of an introduction to the procedure and a baseline HMA assessment. This was followed by a session involving deliberate practice and evaluation using HMA. Subject HMA metrics were followed over time and compared to performance benchmarks to determine the volume of practice required to achieve and maintain technical proficiency in the simulated setting. Performance benchmarks were derived from the assessment of experts using HMA. RESULTS: Subject baseline metrics were significantly different from expert (p < 0.01). At the outset of session 2, none of the subjects achieved the performance benchmarks. At the outset of sessions 3 and 4, 40 and 60% of subjects, respectively, demonstrated retention of technical proficiency. However, there was evidence of significant skill erosion between sessions (p < 0.01). The mean number of practice attempts required to achieve technical proficiency declined between sessions. Regression analysis indicated that there was a significant training effect for all students (overall negative slopes) over time. When examining the group as a whole, the speed at which students reached the expert benchmark was not significantly associated with number of practices in the first three sessions, although for some individuals these factors did appear associated. A total of 76% of subjects retained technical proficiency by session 4 and required a mean of 14 practices (range = 5 to 19). CONCLUSIONS: These results show that the majority of students require three to four sessions of deliberate practice to achieve a sustainable level of proficiency in the LP procedure. There is considerable variation in learning progression and retention of technical proficiency. These results have important implications for the design and resource requirements of a competency-based medical education program targeting LP training. PMID- 26381529 TI - Hypoxia Differentially Regulates Arterial and Venous Smooth Muscle Cell Migration. AB - OBJECTIVE: Intimal hyperplasia (IH) is a clinical concern leading to failure of up to 50% of vein grafts and 10% of arterial grafts after 10 years with no known current treatment. Recent studies have shown that hypoxia differentially regulates proliferation of vein derived smooth muscle cells (V-SMC) compared to artery derived smooth muscle cells (A-SMC). The objective of this study is to evaluate the effect of hypoxia on cellular migration and the mechanisms underlying the differential effects of hypoxia on A-SMC and V-SMC migration. METHODS AND RESULTS: Hypoxic treatment (3-5% O2) of Smooth Muscle Cells (SMC) resulted in differential migration in scratch wound and electric cell substrate impedance sensing (ECIS) assays. Hypoxia led to greater migration compared to normoxia with venous derived wound closure (V-SMC 30.8% Normoxia to 67% Hypoxia) greater than arterial wound closure (A-SMC 6.2% Normoxia to 24.7% Hypoxia). Paracrine factors secreted by hypoxic endothelial cells induced more migration in SMC compared to factors secreted by normoxic endothelial cells. Migration of V SMC was greater than A-SMC in the presence of paracrine factors. Neutralizing antibody to Vascular Endothelial Growth Factor Receptor -1 (VEGFR-1) completely inhibited V-SMC migration while there was only partial inhibition of A-SMC migration. A-SMC migration was completely inhibited by Platelet Derived Growth Factor BB (PDGF-BB) neutralizing antibody. p38 Mitogen Activated Protein kinase (p38 MAPK) inhibitor pre-incubation completely inhibited migration induced by paracrine factors in both A-SMC and V-SMC. CONCLUSION: Our study determines that SMC migration under hypoxia occurs via both an autocrine and paracrine mechanism and is dependent on Vascular Endothelial Growth Factor-A (VEGF-A) in V-SMC and PDGF-BB in A-SMC. Migration of both A-SMC and V-SMC is inhibited by p38 MAPK inhibitor. These studies suggest that pharmacotherapeutic strategies directed at modulating p38 MAPK activity can be exploited to prevent IH in vascular grafts. PMID- 26381530 TI - Everolimus for subependymal giant cell astrocytoma: 5-year final analysis. AB - OBJECTIVE: To analyze the cumulative efficacy and safety of everolimus in treating subependymal giant cell astrocytomas (SEGA) associated with tuberous sclerosis complex (TSC) from an open-label phase II study (NCT00411619). Updated data became available from the conclusion of the extension phase and are presented in this >=5-year analysis. METHODS: Patients aged >= 3 years with a definite diagnosis of TSC and increasing SEGA lesion size (>=2 magnetic resonance imaging scans) received everolimus starting at 3mg/m(2) /day (titrated to target blood trough levels of 5-15ng/ml). The primary efficacy endpoint was reduction from baseline in primary SEGA volume. RESULTS: As of the study completion date (January 28, 2014), 22 of 28 (78.6%) initially enrolled patients finished the study per protocol. Median (range) duration of exposure to everolimus was 67.8 (4.7-83.2) months; 12 (52.2%) and 14 (60.9%) of 23 patients experienced SEGA volume reductions of >=50% and >=30% relative to baseline, respectively, after 60 months of treatment. The proportion of patients experiencing daily seizures was reduced from 7 of 26 (26.9%) patients at baseline to 2 of 18 (11.1%) patients at month 60. Most commonly reported adverse events (AEs) were upper respiratory tract infection and stomatitis of mostly grade 1 or 2 severity. No patient discontinued treatment due to AEs. The frequency of emergence of most AEs decreased over the course of the study. INTERPRETATION: Everolimus continues to demonstrate a sustained effect on SEGA tumor reduction over >=5 years of treatment. Everolimus remained well-tolerated, and no new safety concerns were noted. PMID- 26381531 TI - Establishing a Global Radiation Oncology Collaboration in Education (GRaCE): Objectives and priorities. AB - Representatives from countries and regions world-wide who have implemented modern competency-based radiation- or clinical oncology curricula for training medical specialists, met to determine the feasibility and value of an ongoing international collaboration. In this forum, educational leaders from the ESTRO School, encompassing many European countries adopting the ESTRO Core Curriculum, and clinician educators from Canada, Denmark, the United Kingdom, Australia and New Zealand considered the training and educational arrangements within their jurisdictions, identifying similarities and challenges between programs. Common areas of educational interest and need were defined, which included development of new competency statements and assessment tools, and the application of the latter. The group concluded that such an international cooperation, which might expand to include others with similar goals, would provide a valuable vehicle to ensure training program currency, through sharing of resources and expertise, and enhance high quality radiation oncology education. Potential projects for the Global Radiation Oncology Collaboration in Education (GRaCE) were agreed upon, as was a strategy designed to maintain momentum. This paper describes the rationale for establishing this collaboration, presents a comparative view of training in the jurisdictions represented, and reports early goals and priorities. PMID- 26381532 TI - No prevention of radiotherapy-induced alopecia by scalp cooling. PMID- 26381533 TI - Sexual Concerns after (Pelvic) Radiotherapy: Is There Any Role for the Radiation Oncologist? AB - INTRODUCTION: Sexual function is an important aspect of quality of life, and may be impaired after (pelvic) radiation. AIM: The aim of this study was to identify practice, responsibility attitudes, knowledge, and barriers of Dutch radiation oncologists regarding sexual counseling. METHODS: A cross-sectional survey was performed using a 28-item questionnaire sent to all members of the Dutch Society for Radiotherapy and Oncology. MAIN OUTCOME MEASURES: Self-reported practice, knowledge, barriers, need for training and responsibility attitudes in regard to demographic characteristics. RESULTS: Of the surveyed sample, 54.6% of the radiation oncologists completed the instrument (n = 119). Frequency of discussing sexual function was fluctuating, depending on the type of tumor. The majority of the responding radiation oncologists (75%) agreed that discussing sexual function is their responsibility, about one-third (33.6%) pointed at the involved specialist (surgeon, urologist, gynecologist, or oncologist), a fifth also considered the general practitioner responsible (21%). Additional training about discussing sexuality was required according to 44.4%, the majority agreed that sexual counseling should be a regular component of radiation oncology residency (n = 110, 94%). Barriers most mentioned included patient is too ill (36.2%), no angle or reason for asking (32.4%), advanced age of the patient (27%) and culture/religion (26.1%). For prostate cancer patients, phosphodiesterase 5 inhibitor information was supplied regularly (49.2%) and often (40.7%). CONCLUSIONS: Radiation oncologists generally perform sexual counseling in case of pelvic radiation therapy, but not consistently in case of gastrointestinal, breast, and other cancers. The majority of radiation oncologists considered counseling on sexual functioning as a part of their job, some also pointed at the referring specialist or general practitioner. The findings suggest that awareness about sexual dysfunction is present among radiation oncologists, but responsibility for active counseling is uncertain. Results emphasize the need for providing educational and practical training, as well as a list for specialized referral. PMID- 26381534 TI - Relation of Lipid Content of Coronary Plaque to Level of Serum Uric Acid. AB - Elevated serum uric acid (SUA) level is known to be a prognostic factor in patients with acute coronary syndrome (ACS). However, the pathogenesis of the relation between SUA level and coronary plaque characteristics has not been fully evaluated. The aim of this study was to investigate the relation between SUA level and plaque composition of nonculprit lesions in patients with ACS. A total of 81 patients with ACS who underwent intravascular ultrasound (IVUS)-guided percutaneous coronary intervention were included. They were classified into 3 groups according to tertiles of SUA level. Using integrated backscatter (IB)-IVUS system, tissue components were classified into 4 categories: calcium deposits, dense fibrosis, fibrosis, and lipid. Tertiles of SUA level were as follows: low tertile <5.0 mg/dl; intermediate tertile 5.0 to 6.4 mg/dl; and high tertile >6.4 mg/dl. There was a trend toward greater vessel volume in the high tertile group than in the low and intermediate tertile groups (19.4 +/- 3.7 vs 17.4 +/- 4.4 vs 16.7 +/- 4.1 mm(3)/mm, p = 0.05). There was no significant difference in lumen volume between the 3 groups. Plaque volume was significantly greater in the high than in the low tertile group (8.6 +/- 2.4 vs 6.7 +/- 2.2 mm(3)/mm, p = 0.01). IB IVUS analysis demonstrated greater lipid (59.1 +/- 9.1% vs 49.7 +/- 10.9% vs 51.1 +/- 9.3%, p = 0.001) and less fibrous components (36.8 +/- 7.8% vs 44.3 +/- 7.8% vs 43.2 +/- 6.7%, p <0.001) in the high than in the low and intermediate tertile groups. Multivariate analysis showed high SUA as an independent predictor of increasing lipid volume. In conclusion, elevated SUA level is associated with greater lipid content of coronary plaque in patients with ACS than in patients with normal levels. PMID- 26381535 TI - Exercise capacity and heart rate responses to exercise as predictors of short term outcome among patients with stable coronary artery disease. AB - Although exercise capacity (EC) and autonomic responses to exercise predict clinical outcomes in various populations, they are not routinely applied in patients with coronary artery disease (CAD). We hypothesized that the composite index of EC and exercise heart rate responses would be a powerful determinant of short-term risk in CAD. Patients with angiographically documented stable CAD and treated with beta blockers (n = 1,531) underwent exercise testing to allow the calculation of age- and gender-adjusted EC, maximal chronotropic response index (CRI), and 2-minute postexercise heart rate recovery (HRR, percentage of maximal heart rate). Cardiovascular deaths and hospitalization due to heart failure, registered during a 2-year follow-up (n = 39, 2.5%), were defined as the composite primary end point. An exercise test risk score was calculated as the sum of hazard ratios related to abnormal (lowest tertile) EC, CRI, and HRR. Abnormal EC, CRI, and HRR predicted the primary end point, involving 4.5-, 2.2-, and 6.2-fold risk, respectively, independently of each other. The patients with intermediate and high exercise test risk score had 11.1-fold (95% confidence interval 2.4 to 51.1, p = 0.002) and 25.4-fold (95% confidence interval 5.5 to 116.8, p <0.001) adjusted risk for the primary end point in comparison with the low-risk group, respectively. The addition of this risk score to the established risk model enhanced discrimination by integrated discrimination index and reclassification by categorical and continuous net reclassification index (p <0.001 for all). In conclusion, the composite index of EC and heart rate responses to exercise and recovery is a powerful predictor of short-term outcome in patients with stable CAD. PMID- 26381536 TI - Cellular misfolded proteins rescued from degradation by MHC class II molecules are possible targets for autoimmune diseases. AB - The major function of major histocompatibility complex (MHC) class II molecules is the presentation of peptide antigens to helper T cells. However, when misfolded proteins are associated with MHC class II molecules in the endoplasmic reticulum, they are transported to the cell surface by MHC class II molecules without processing to peptides. Of note, misfolded proteins complexed with MHC class II molecules are specifically recognized by autoantibodies produced in patients with autoimmune diseases such as rheumatoid arthritis and antiphospholipid syndrome. Furthermore, autoantibody binding to misfolded proteins complexed with MHC class II molecules is associated with the susceptibility to autoimmune diseases conferred by each MHC class II allele. Therefore, misfolded proteins rescued from degradation by MHC class II molecules may be recognized as 'neo-self' antigens by the immune system and be involved in the pathogenicity of autoimmune diseases. PMID- 26381537 TI - Ethrel-stimulated prolongation of latex flow in the rubber tree (Hevea brasiliensis Muell. Arg.): an Hev b 7-like protein acts as a universal antagonist of rubber particle aggregating factors from lutoids and C-serum. AB - Ethrel is the most effective stimuli in prolonging the latex flow that consequently increases yield per tapping. This effect is largely ascribed to the enhanced lutoid stability, which is associated with the decreased release of initiators of rubber particle (RP) aggregation from lutoid bursting. However, the increase in both the bursting index of lutoids and the duration of latex flow after applying ethrel or ethylene gas in high concentrations suggests that a new mechanism needs to be introduced. In this study, a latex allergen Hev b 7-like protein in C-serum was identified by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI TOF MS). In vitro analysis showed that the protein acted as a universal antagonist of RP aggregating factors from lutoids and C-serum. Ethrel treatment obviously weakened the effect of C-serum on RP aggregation, which was closely associated with the increase in the level of the Hev b 7-like protein and the decrease in the level of the 37 kDa protein, as revealed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS PAGE), western blotting analysis and antibody neutralization. Thus, the increase of the Hev b 7-like protein level or the ratio of the Hev b 7-like protein to the 37 kDa protein in C-serum should be primarily ascribed to the ethrel-stimulated prolongation of latex flow duration. PMID- 26381538 TI - Bacterial Community Structure and Dynamics During Corn-Based Bioethanol Fermentation. AB - Corn-based fuel ethanol facilities mix enzymatically treated, gelatinized corn starch with water to generate a "mash" that is used as the substrate in large scale (~500,000 gallon) yeast-based fermentations. In contrast to other food and beverage fermentations (e.g., cheese, wine), bioethanol production is presumed to be optimal when bacteria are absent from the fermentation-thus maximizing conversion of glucose to ethanol-yet the facilities are not sterilized. Culture based analysis has suggested that lactic acid bacteria occupy this niche and, under certain circumstances, can outcompete the dedicated fermentation yeast for nutrients. Here, we use 16S rRNA gene amplicon sequencing to probe bacterial community structure during bioethanol fermentation. Nineteen total batches from five corn-based fuel ethanol fermentation facilities were analyzed. From each batch, five samples were taken. This includes the contents of the yeast propagation tank at inoculation, three samples taken at intervals during the fermentation, and a sample taken at the end of fermentation. Bacterial community structure was compared with time, between facility, between fermentor, between batches from the same fermentor, and against environmental variables within each fermentation. Communities were dominated by members of the Firmicutes and Proteobacteria phyla, with lactic acid bacteria dominating the communities in two of the five facilities. In the other facilities, Proteobacteria (largely members of the Pseudomonas and Escherichia-Shigella genera) outcompete the lactic acid bacteria. In most cases, the yeast propagation tank inoculum imparted a rich bacterial community, but the batches vary regarding whether this inoculum was the primary driver of the fermentation community structure. PMID- 26381540 TI - Experiences on two different stereotactic radiosurgery modalities of Gamma Knife and Cyberknife in treating brain metastases. AB - BACKGROUND: In this study, we compared the dosimetric properties between Gamma Knife (GK) and Cyberknife (CK), and investigated the clinical implications in treating brain metastases (BMs). METHODS: Between 2011 and 2013, 77 patients treated with either single-fraction GK for small BMs (n = 40) or fractionated CK for large BMs >3 cm (n = 37) were analyzed. Among a total of 160 lesions, 81 were treated with GK (median, 22 Gy) and 38 (large lesions) with three- or five fraction CK (median, 35 Gy). The median tumor volume was 1.0 cc (IQR, 0.12-4.4 cc) for GK and 17.6 cc (IQR, 12.8-23.7 cc) for fractionated CK. A lesion-to lesion dosimetric comparison was performed using the identical contour set in both systems. RESULTS: The mean dose to tumor was significantly higher in GK by 1.25-fold (P < 0.001), whereas normal tissue volume receiving 90-10 % of prescription dose was significantly larger in CK by 1.26-fold (P < 0.001). Nevertheless, no differences were observed in local tumor control (rates at 1 year, 89.7 % vs 87.0 %; P = 0.594) and overall survival (median, 14 vs 16 months; P = 0.493) between GK and fractionated CK groups. The incidences of radiation necrosis were also not different (12.3 % vs 15.8 %; P = 0.443). CONCLUSIONS: Despite slightly inferior dosimetric properties of CK, fractionated CK for large BMs appears to be as effective and safe as single-fraction GK for small BMs, representing fractionation as an effective strategy for enhancing efficacy and moderating toxicity in stereotactic radiosurgery for BMs. PMID- 26381539 TI - A House for Two--Double Bacterial Infection in Euplotes woodruffi Sq1 (Ciliophora, Euplotia) Sampled in Southeastern Brazil. AB - Several ciliated protists form symbiotic associations with a diversity of microorganisms, leading to drastic impact on their ecology and evolution. In this work, two Euplotes spp. sampled in Rio de Janeiro, Brazil, were identified based on morphological and molecular features as Euplotes woodruffi strain Sq1 and E. encysticus strain Sq2 and investigated for the presence of endosymbionts. While E. woodruffi Sq1 stably hosts two bacterial populations, namely Polynucleobacter necessarius (Betaproteobacteria) and a new member of the family "Candidatus Midichloriaceae" (Alphaproteobacteria, Rickettsiales), here described as "Candidatus Bandiella woodruffii," branching with a broad host range bacterial group found in association with cnidarians, sponges, euglenoids, and some arthropods; in E. encysticus Sq2 no symbiotic bacterium could be detected. The dispersion ability of this novel bacterium was tested by co-incubating E. woodruffi Sq1 with three different ciliate species. Among the tested strains "Ca. B. woodruffii" could only be detected in association with E. encysticus Sq2 with a prevalence of 20 % after 1 week and 40 % after 2 weeks, maintaining this level for up to 6 months. Nevertheless, this apparent in vitro association was abolished when E. woodruffi Sq1 donor was removed from the microcosm, suggesting that this bacterium has the capacity for at least a short-term survival outside its natural host and the aptitude to ephemerally interact with other organisms. Together, these findings strongly suggest the need for more detailed investigations to evaluate the host range for "Ca. B. woodruffii" and any possible pathogenic effect of this bacterium on other organisms including humans. PMID- 26381542 TI - Tumor microenvironment in diffuse large B-cell lymphoma: Matrixmetalloproteinases activation is mediated by osteopontin overexpression. AB - Non-Hodgkin lymphomas (NHL) are a heterogeneous group of lymphoproliferative malignancies with variable patterns of behavior and responses to therapy. NHL development and invasion depend on multiple interactions between tumor cells and non-neoplastic cells. Such interactions are usually modulated by several cytokines. Accordingly, it was demonstrated that matrix-metalloproteinase (MMP)-2 and MMP-9 were activated in human lymphoid cell lines by interleukin-6 (IL-6). The activation of these enzymes is associated with tumor invasion and metastasis in human cancers. MMPs are also activated in several cancers by osteopontin (OPN), a secreted glycoprotein that regulates cell adhesion, migration, and survival. However, it is still unclear if MMPs play a role in NHL development and if their activation is determined by OPN and/or IL-6. In the present study, two groups of 78 NHL patients and 95 healthy donors were recruited for the analysis of OPN, MMP-2, MMP-9 and IL-6.Significant higher circulating levels of MMP-2, MMP 9, OPN and IL-6 were observed in NHL patients when compared to healthy donors. Similar data were obtained by analyzing the activity of both MMP-2 and MMP-9. The multivariate regression model indicates that, in both NHL cases and healthy donors, OPN is associated with the increase of MMP-2 and MMP-9 levels independently of IL-6. These data were first confirmed by "in silico" analyses and then by "in vitro" experiments conducted on peripheral blood mononuclear cells randomly selected from both NHL patients and healthy donors.Overall, our data suggest that the activation of MMPs in NHL development is mostly associated with OPN. However, IL-6 may play an important role in the lymphomagenesis through the activation of other molecular pathways. This article is part of a Special Issue entitled: Tumor Microenvironment Regulation of Cancer Cell Survival, Metastasis, Inflammation, and Immune Surveillance edited by Peter Ruvolo and Gregg L. Semenza. PMID- 26381541 TI - De novo peroxisome biogenesis: Evolving concepts and conundrums. AB - Peroxisomes proliferate by growth and division of pre-existing peroxisomes or could arise de novo. Though the de novo pathway of peroxisome biogenesis is a more recent discovery, several studies have highlighted key mechanistic details of the pathway. The endoplasmic reticulum (ER) is the primary source of lipids and proteins for the newly-formed peroxisomes. More recently, an intricate sorting process functioning at the ER has been proposed, that segregates specific PMPs first to peroxisome-specific ER domains (pER) and then assembles PMPs selectively into distinct pre-peroxisomal vesicles (ppVs) that later fuse to form import-competent peroxisomes. In addition, plausible roles of the three key peroxins Pex3, Pex16 and Pex19, which are also central to the growth and division pathway, have been suggested in the de novo process. In this review, we discuss key developments and highlight the unexplored avenues in de novo peroxisome biogenesis. PMID- 26381543 TI - Body Image in Adolescents - A Clinical Issue. PMID- 26381544 TI - Precocious Puberty, GnRH Stimulation Test and Monitoring GnRH Analog Therapy. PMID- 26381545 TI - Sequential Therapy is Superior to Triple Therapy for Helicobacter pylori Infection in Children: A Meta-Analysis. AB - OBJECTIVES: To assess the efficacy and safety of 10-d sequential therapy compared to 5 to 14-d triple therapy for treating Helicobacter pylori infections in children according to the eradication rates. METHODS: The Cochrane Library, MEDLINE, EMBASE, China National Knowledge Infrastructure databases, and other sources were searched in November 2014 without language restrictions. Randomized controlled trials (RCTs) that compared sequential therapy with triple therapy for H. pylori eradication in children were included. Dichotomous data were pooled to obtain the relative risk (RR) of the eradication rate with a 95% confidence interval (CI). RESULTS: Fourteen RCTs with 1698 participants (718 and 980 for sequential and triple therapy, respectively) were included. The intention-to treat eradication rates were 73% (95% CI: 70-76) and 66% (95% CI: 64-70) for sequential and triple therapy, respectively. The pooled RR was 1.16 (95% CI: 1.09 1.23), resulting in a number needed to treat of 16 (95% CI: 10-48), favoring sequential therapy. Sequential therapy was superior to 7- and 10-d triple therapy. Sequential and triple therapy did not differ significantly in the overall risk of adverse effects. CONCLUSIONS: In children, sequential therapy appears to be superior to triple therapy for H. pylori eradication, although the eradication rates remain lower than the expected goal with both treatments. Factors-associated with a higher risk of eradication failure, such as compliance and antimicrobial resistance, remain insufficiently investigated. Therefore, further high-quality RCTs are needed to compare these different eradication treatment approaches. PMID- 26381546 TI - Investigations of selected pathogens among village pigs in Central Papua, Indonesia. AB - Village pig husbandry is an important part of livestock production in Papua Province, Eastern Indonesia. However, high level of disease and mortality constrains production. The aim of this study was to investigate the prevalence of the selected pathogens in village pigs in the Jayawijaya Region of Papua Province, Indonesia. Two studies were conducted: Study 1 determined the prevalence of selected pathogens in dead or moribund pigs sent to the main local market for sale. Study 2 recorded the prevalence of the selected pathogens, on pig farms in the Subdistrict of Wamena that had not recorded a case of pig mortality during the duration of Study 1. Blood samples of individuals from both groups were tested for CSF antigen and antibody, as well as antibody against PCV2. Organs with evident pathological changes from Study 1 and tonsilar swabs from Study 2 were subjected to bacteriological culture and identification of Streptococcus suis and Streptococcus zooepidemicus. Faecal samples from both studies were examined for eggs of strongyle parasites, Trichuris suis, Ascaris suum, Strongyloides ransomi and coccidia. The main infections in both studies were CSF, PCV2 and strongyle parasites, but prevalence was higher in Study 1 (P < 0.05). T. suis and S. zooepidemicus were prevalent in pigs in Study 1, but rare in healthy pigs (P < 0.05). Infections with coccidia, A. suum and S. ransomi were common but did not differ between groups (P < 0.05), with S. suis infections uncommon in both studies. This suggests that infections with CSF, PCV2, strongyle and T. suis are important pathogens in village pig farms in Jayawijaya. Local pig husbandry practices, such as confining pigs and heat-treating pig feeds, may be practical solutions to help minimize infection in village pigs in Jayawijaya. PMID- 26381547 TI - Synthesis and Structure of Hypervalent Iodine(III) Reagents Containing Phthalimidate and Application to Oxidative Amination Reactions. AB - A new class of hypervalent iodine reagents containing phthalimidate was synthesized, and structurally characterized by X-ray analysis. The benziodoxole based reagent displays satisfactory solubility in common organic solvents and is reasonably stable in solution as well as in the solid state. The reagent was used for the oxidative amination of the C(sp(3))-H bond of N,N-dimethylanilines. In addition, the reagent was also applicable to oxidative amination with rearrangement of trialkylamines as well as enamines that were prepared in situ from secondary amines and aldehydes. PMID- 26381548 TI - Author's reply to Datta. PMID- 26381549 TI - Cost-effectiveness of Occupational Therapy in Older People: Systematic Review of Randomized Controlled Trials. AB - A systematic review of the cost-effectiveness of occupational therapy for older people was conducted. MEDLINE, CINAHL, Web of Science, PsycINFO, Cochrane Library, OT seeker and unpublished trials registers were searched. Reference lists of all potentially eligible studies were searched with no language restrictions. We included trial-based full economic evaluations that considered both costs and outcomes in occupational therapy for older people compared with standard care (i.e. other therapy) or no intervention. We reviewed each trial for methodological quality using the Cochrane risk of bias tool and assessed the quality of economic evaluations using a Drummond checklist. In the results of this review, we included five eligible studies (1-5) that were randomized controlled trials with high-quality economic evaluation. Two studies were full economic evaluations of interventions for fall prevention (1 and 2); two studies were full economic evaluations of preventive occupational therapy interventions (3 and 4; one was a comparison of an occupational therapy group with a social work group); one study was a full economic evaluation of occupational therapy for individuals with dementia (5). Two of the studies (one was preventive occupational therapy [3] and the other was occupational therapy for dementia [5]) found a significant effect and confirmed the cost-effectiveness of occupational therapy for older people compared with the control group. These studies found that occupational therapy for older people was clinically effective and cost effective in comparison with standard care or other therapies. With reference to their clinical implication, these intervention studies (using a client-centred approach) suggested potentially cost-effective means to motivate clients to maintain their own health. However, this review has limitations because of the high heterogeneity of the reviewed studies on full economic evaluations of occupational therapy for older people. Future studies on the cost-effectiveness of occupational therapy in older people are strongly warranted. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26381550 TI - Cancer incidence among Minnesota taconite mining industry workers. AB - PURPOSE: To evaluate cancer incidence among Minnesota taconite mining workers. METHODS: We evaluated cancer incidence between 1988 and 2010 in a cohort of 40,720 Minnesota taconite mining workers used between 1937 and 1983. Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) were estimated by comparing numbers of incident cancers with frequencies in the Minnesota Cancer Surveillance System. SIRs for lung cancer by histologic subtypes were also estimated. We adjusted for out-of-state migration and conducted a probabilistic bias analysis for smoking-related cancers. RESULTS: A total of 5700 cancers were identified, including 51 mesotheliomas and 973 lung cancers. The SIRs for lung cancer and mesothelioma were 1.3 (95% CI = 1.2-1.4) and 2.4 (95% CI = 1.8-3.2), respectively. Stomach, laryngeal, and bladder cancers were also elevated. However, adjusting for potential confounding by smoking attenuated the estimates for lung (SIR = 1.1, 95% CI = 1.0-1.3), laryngeal (SIR = 1.2, 95% CI = 0.8-1.6), oral (SIR = 0.9, 95% CI = 0.7-1.2), and bladder cancers (SIR = 1.0, 95% CI = 0.8 1.1). CONCLUSIONS: Taconite workers may have an increased risk for certain cancers. Lifestyle and work-related factors may play a role in elevated morbidity. The extent to which mining-related exposures contribute to disease burden is being investigated. PMID- 26381551 TI - The Arcuate Fasciculus and Language Development in a Cohort of Pediatric Patients with Malformations of Cortical Development. AB - BACKGROUND AND PURPOSE: Patients with epilepsy and malformations of cortical development have a high prevalence of language deficits. The purpose of this study was to investigate whether the status of the arcuate fasciculus at diffusion tractography could provide a clinically meaningful marker of language function in patients with cortical malformations. MATERIALS AND METHODS: Thirty seven patients 3-18 years of age who had DTI performed at 3T and language evaluation by a pediatric neurologist were retrospectively identified. Twenty-two age-matched children without any neurologic, language, or MR imaging abnormalities who had identical DTI performed for an indication of headache were selected as a control cohort. The arcuate fasciculi were constructed and segmented by deterministic tractography for all subjects. RESULTS: Twenty-one patients had intact language; 11 had mild-to-moderate and 5, profound language impairment. All patients with normal language and all control subjects had an identifiable left arcuate. The left arcuate was absent in 11 patients; all 11 were language-impaired. Failure to identify the left arcuate was strongly associated with some degree of language impairment (P < .001). Sensitivity, specificity, and positive predictive value for language dysfunction were 65%, 100%, and 100%, respectively. The absence of the arcuate bilaterally was associated with complete failure to develop oral language (P < .015). CONCLUSIONS: Failure to identify the left arcuate fasciculus at diffusion tractography was a highly specific marker of language dysfunction in a cohort of pediatric patients with malformations of cortical development. Failure to identify the arcuate fasciculus on either side was associated with failure to develop oral language. PMID- 26381552 TI - Asymmetry of the Odontoid Lateral Mass Interval in Pediatric Trauma CT: Do We Need to Investigate Further? AB - BACKGROUND AND PURPOSE: Odontoid lateral mass interval asymmetry can be within the normal spectrum or the result of traumatic atlantoaxial injury. We sought to set radiographic guidelines for further investigation of odontoid lateral mass interval asymmetry in cervical spine CT studies of pediatric trauma patients. MATERIALS AND METHODS: Fourteen children with C1-2 ligamentous injury or atlantoaxial rotational fixation/subluxation were retrospectively identified. We identified an additional 56 children fulfilling the following inclusion criteria: 1) They underwent C-spine CT to exclude traumatic injury, and 2) C-spine clearance and follow-up. Those were matched for age, sex, and severity of traumatic insult with the injured group. Clinical data were collected, and we measured the following parameters: anterior atlantodental interval; odontoid lateral mass interval; and the rotation of the head, C1, and C2. RESULTS: A significant difference (P < .001) was found between the groups in cervical tenderness and torticollis. There was a significant difference in the atlantodental interval value (3.3 +/- 0.8 mm in injured and 2.2 +/- 0.5 mm in noninjured). The directionality of head, C1, and C2 rotation was significantly (P < .05) more toward the same direction in the noninjured group. We found significant linear correlation between head rotation and ipsilateral odontoid lateral mass interval asymmetry only in the noninjured at C1-2. With multivariant analysis, the presence of cervical tenderness and an abnormal atlantodental interval were the most significant variables. CONCLUSIONS: Odontoid lateral mass interspace asymmetry in the absence of cervical tenderness and with a normal atlantodental interval is likely in the normal range and need not be further investigated. PMID- 26381553 TI - The Combined Performance of ADC, CSF CXC Chemokine Ligand 13, and CSF Interleukin 10 in the Diagnosis of Central Nervous System Lymphoma. AB - BACKGROUND AND PURPOSE: CXC chemokine ligand 13 and interleukin 10 have emerged as CSF biomarkers for the diagnosis of CNS lymphoma. Our hypothesis is that the combined use of ADC, CXC chemokine ligand 13, and interleukin 10 will result in increased diagnostic performance compared with the use of ADC values alone. MATERIALS AND METHODS: Eighty-seven patients were included in this study, including 43 with CNS lymphoma and 44 without CNS lymphoma (21 metastases, 14 high-grade gliomas, 9 tumefactive demyelinating lesions) who had undergone CSF proteomic analysis and had a new enhancing mass on brain MR imaging. Average ADC was derived by contouring the contrast-enhancing tumor volume. Group means were compared via t tests for average ADC, CXC chemokine ligand 13, and interleukin 10. Receiver operating characteristic analysis was performed for each individual variable. Multiple-variable logistic regression with receiver operating characteristic analysis was performed, and the multiple-variable receiver operating characteristic was compared with single-variable receiver operating characteristics. RESULTS: The average ADC was lower and CSF CXC chemokine ligand 13 and interleukin 10 values were higher in CNS lymphoma (P < .001). Areas under the curve ranged from 0.739 to 0.832 for single-variable ROC. Multiple-variable logistic regression yielded statistically significant individual effects for all 3 variables in a combined model. Multiple-variable receiver operating characteristics (area under the curve, 0.928) demonstrated statistically significantly superior diagnostic performance compared with the use of single variables alone. CONCLUSIONS: The combined use of ADC, CSF CXC chemokine ligand 13, and interleukin 10 results in increased diagnostic performance for the diagnosis of CNS lymphoma. This finding highlights the importance of CSF analysis when the diagnosis of CNS lymphoma is considered on the basis of MR imaging. PMID- 26381554 TI - The Revascularization Scales Dilemma: Is It Right to Apply the Treatment in Cerebral Ischemia Scale in Posterior Circulation Stroke? AB - BACKGROUND AND PURPOSE: Although various revascularization scales are used in the angiographic evaluation of acute ischemic stroke, observer reliability tests of these scales have been rarely performed for posterior circulation stroke. We aimed to evaluate inter- and intraobserver variability of 2 scales, the modified Treatment in Cerebral Ischemia and the Arterial Occlusive Lesion, in posterior circulation stroke. MATERIALS AND METHODS: Three independent readers interpreted pre- and postthrombolytic angiographies of 62 patients with posterior circulation stroke by using the modified Treatment in Cerebral Ischemia and Arterial Occlusive Lesion scales. The kappa statistic was used to measure observer agreement for both scales, and kappa > 0.6 was considered substantial agreement. RESULTS: For the Arterial Occlusive Lesion scale, inter- and intraobserver agreement was >0.6. While intraobserver agreement of the modified Treatment in Cerebral Ischemia scale was >0.6 except for 1 reader, interobserver agreement was lower in dichotomized and original scales. In 49 cases with solely basilar artery occlusion, inter- and intraobserver agreement of both scales was similar to that in all 62 patients with posterior circulation stroke. In 2 consecutive readings, there was a significant decrease in the proportion of mTICI 2a reads (22.58% in the first versus 13.44% in the second session, P < .03) and a reciprocal increase in the sum of proportions for modified Treatment in Cerebral Ischemia 2b and modified Treatment in Cerebral Ischemia 3 reads (62.37% in the first versus 72.58% in the second session, P < .046). CONCLUSIONS: In angiographic assessment of posterior circulation stroke, inter- and intraobserver agreement for the Arterial Occlusive Lesion scale was reliable, while the modified Treatment in Cerebral Ischemia failed to achieve substantial interobserver agreement. The clinical impact of this result needs to be validated in future studies. PMID- 26381555 TI - Minimizing Radiation Exposure in Evaluation of Pediatric Head Trauma: Use of Rapid MR Imaging. AB - BACKGROUND AND PURPOSE: With >473,000 annual emergency department visits for children with traumatic brain injuries in the United States, the risk of ionizing radiation exposure during CT examinations is a real concern. The purpose of this study was to assess the validity of rapid MR imaging to replace CT in the follow up imaging of patients with head trauma. MATERIALS AND METHODS: A retrospective review of 103 pediatric patients who underwent initial head CT and subsequent follow-up rapid MR imaging between January 2010 and July 2013 was performed. Patients had minor head injuries (Glasgow Coma Scale, >13) that required imaging. Initial head CT was performed, with follow-up rapid MR imaging completed within 48 hours. A board-certified neuroradiologist, blinded to patient information and scan parameters, then independently interpreted the randomized cases. RESULTS: There was almost perfect agreement in the ability to detect extra-axial hemorrhage on rapid MR imaging and CT (kappa = 0.84, P < .001). Evaluation of hemorrhagic contusion/intraparenchymal hemorrhage demonstrated a moderate level of agreement between MR imaging and CT (kappa = 0.61, P < .001). The ability of MR imaging to detect a skull fracture also showed a substantial level of agreement with CT (kappa = 0.71, P < .001). Detection of diffuse axonal injury demonstrated a slight level of agreement between MR imaging and CT (kappa = 0.154, P = .04). However, the overall predictive agreement for the detection of an axonal injury was 91%. CONCLUSIONS: Rapid MR imaging is a valid technique for detecting traumatic cranial injuries and an adequate examination for follow-up imaging in lieu of repeat CT. PMID- 26381556 TI - Diagnostic and Prognostic Value of 11C-Methionine PET for Nonenhancing Gliomas. AB - BACKGROUND AND PURPOSE: Noninvasive radiologic evaluation of glioma can facilitate correct diagnosis and detection of malignant transformation. Although positron-emission tomography is considered valuable in the care of patients with gliomas, (18)F-fluorodeoxyglucose and (11)C-methionine have reportedly shown ambiguous results in terms of grading and prognostication. The present study compared the diagnostic and prognostic capabilities of diffusion tensor imaging, FDG, and (11)C-methionine PET in nonenhancing gliomas. MATERIALS AND METHODS: Thirty-five consecutive newly diagnosed, histologically confirmed nonenhancing gliomas that underwent both FDG and (11)C-methionine PET were retrospectively investigated (23 grade II and 12 grade III gliomas). Apparent diffusion coefficient, fractional anisotropy, and tumor-to-normal tissue ratios of both FDG and (11)C-methionine PET were compared between grade II and III gliomas. Prognostic values of these parameters were also tested by using progression-free survival. RESULTS: Grade III gliomas showed significantly higher average tumor-to normal tissue and maximum tumor2-to-normal tissue than grade II gliomas in (11)C methionine (P = .013, P = .0017, respectively), but not in FDG-PET imaging. There was no significant difference in average ADC, minimum ADC, average fractional anisotropy, and maximum fractional anisotropy. (11)C-methionine PET maximum tumor to-normal tissue ratio of 2.0 was most suitable for detecting grade III gliomas among nonenhancing gliomas (sensitivity, 83.3%; specificity, 73.9%). Among patients not receiving any adjuvant therapy, median progression-free survival was 64.2 +/- 7.2 months in patients with maximum tumor-to-normal tissue ratio of <2.0 for (11)C-methionine PET and 18.6 +/- 6.9 months in patients with maximum tumor to-normal tissue ratio of >2.0 (P = .0044). CONCLUSIONS: (11)C-methionine PET holds promise for World Health Organization grading and could offer a prognostic imaging biomarker for nonenhancing gliomas. PMID- 26381557 TI - Endovascular Treatment of Ruptured Blister-Like Aneurysms: A Systematic Review and Meta-Analysis with Focus on Deconstructive versus Reconstructive and Flow Diverter Treatments. AB - BACKGROUND AND PURPOSE: Various endovascular techniques have been applied to treat blister-like aneurysms. We performed a systematic review to evaluate endovascular treatment for ruptured blister-like aneurysms. MATERIALS AND METHODS: We performed a comprehensive literature search and subgroup analyses to compare deconstructive versus reconstructive techniques and flow diversion versus other reconstructive options. RESULTS: Thirty-one studies with 265 procedures for ruptured blister-like aneurysms were included. Endovascular treatment was associated with a 72.8% (95% CI, 64.2%-81.5%) mid- to long-term occlusion rate and a 19.3% (95% CI, 13.6%-25.1%) retreatment rate. Mid- to long-term neurologic outcome was good in 76.2% (95% CI, 68.9%-8.4%) of patients. Two hundred forty procedures (90.6%) were reconstructive techniques (coiling, stent-assisted coiling, overlapped stent placement, flow diversion) and 25 treatments (9.4%) were deconstructive. Deconstructive techniques had higher rates of initial complete occlusion than reconstructive techniques (77.3% versus 33.0%, P = .0003) but a higher risk for perioperative stroke (29.1% versus 5.0%, P = .04). There was no difference in good mid- to long-term neurologic outcome between groups, with 76.2% for the reconstructive group versus 79.9% for the deconstructive group (P = .30). Of 240 reconstructive procedures, 62 (25.8%) involved flow-diverter stents, with higher rates of mid- to long-term complete occlusion than other reconstructive techniques (90.8% versus 67.9%, P = .03) and a lower rate of retreatment (6.6% versus 30.7%, P < .0001). CONCLUSIONS: Endovascular treatment of ruptured blister-like aneurysms is associated with high rates of complete occlusion and good mid- to long-term neurologic outcomes in most patients. Deconstructive techniques are associated with higher occlusion rates but a higher risk of perioperative ischemic stroke. In the reconstructive group, flow diversion carries a higher level of complete occlusion and similar clinical outcomes. PMID- 26381558 TI - Combination of Multicatheter Plus Stent or Balloon for Treatment of Complex Aneurysms. AB - BACKGROUND AND PURPOSE: Coiling of complex aneurysms is still difficult even with current adjuvant techniques. This study sought to evaluate the safety and effectiveness of a combination of multicatheter plus stent or balloon for the treatment of complex aneurysms. MATERIALS AND METHODS: All complex aneurysms that underwent coiling with the combination technique were identified from prospectively maintained neurointerventional data bases. "Complex aneurysm" was defined as a wide-neck aneurysm with branch incorporation into or a deep lobulation of the sac. The clinical and angiographic outcomes were retrospectively analyzed. RESULTS: Sixty-two complex aneurysms (12 ruptured, 50 unruptured) in 62 patients (mean age, 57 years; male/female ratio, 12:50) were treated with a combination technique by using a multicatheter plus stent (n = 42, 3 ruptured) or balloon (n = 20, 9 ruptured). Treatment-related morbidity (grade 3 hemiparesis) occurred in 1 patient (1.6%). Except for 1 patient who had treatment related morbidity, none of the other patients with unruptured aneurysms developed new neurologic symptoms at discharge. Nine of the 12 patients with ruptured aneurysms had good outcomes (Glasgow Outcome Score, 4 or 5) at the latest follow up (mean, 32 months; range, 6-72 months), and 1 patient died from an initial SAH. Posttreatment control angiograms revealed complete occlusion in 27, neck remnant in 34, and incomplete occlusion in 1 aneurysm. At least 1 follow-up catheter or MR angiogram was available in 80.6% (n = 50) (mean, 21 months; range, 6-65 months). There were 4 minor and 3 major recurrences (14.0%). CONCLUSIONS: In this case series, the combination technique by using multicatheter plus stent or balloon seemed safe and effective for the treatment of complex aneurysms. PMID- 26381559 TI - Multiple Procedure Payment Reduction: Health Policy Update. AB - Multiple Procedure Payment Reduction currently applies to multiple diagnostic imaging services administered to the same patient during the same day and entails a 50% decrease in the technical component and a 25% decrease in the professional component reimbursement. This might change with time due to further legislation, so it is important to be up-to-date on these health policy developments. PMID- 26381560 TI - An Enhanced Model of Middle Cerebral Artery Occlusion in Nonhuman Primates Using an Endovascular Trapping Technique. AB - BACKGROUND AND PURPOSE: Current nonhuman primate stroke models are limited by either stroke variability or survivability. A new nonhuman primate stroke model was developed by using endovascular trapping techniques to limit collateral vessels with serial MR imaging and neurologic assessments. MATERIALS AND METHODS: Eight adult rhesus monkeys (female, 7-13 years of age) underwent MR imaging and Spetzler neurologic assessment followed by endovascular stroke induction consisting of superselective endovascular placement of surgical silk sutures into the right MCA by using a trapping technique. Two initial subjects were euthanized immediately following postocclusion MR imaging. The subsequent 6 subjects recovered and underwent follow-up MR imaging and Spetzler neurologic assessments at 48 hours, with 4 being followed to 96 hours. Stroke infarct volumes were measured, and the longitudinal Spetzler clinical neurologic scores were assessed. The brain tissues were harvested and prepared with hematoxylin-eosin staining. RESULTS: Focal permanent cerebral ischemia was induced in the targeted right MCA territory in all subjects. The volumes of the ischemic lesions at 6, 48, and 96 hours were 3.18 +/- 1.007 mL (standard error of the mean) (n = 8), 6.70 +/- 1.666 mL (standard error of the mean) (n = 6), and 7.23 +/- 1.371 mL (standard error of the mean) (n = 4). For the survival animals, the immediate postsurgical Spetzler grading score improved from 60.7 at 24 hours to 68.7 at 48 hours. CONCLUSIONS: We report a trapping modification to an established endovascular suture stroke model that yielded reproducible ischemia and clinically quantifiable neurologic deficits with no strokes in nontarget areas. This technique may be useful in evaluating translational stroke and penumbral imaging research in addition to preclinical testing of neuroprotective therapies. PMID- 26381561 TI - Endolymphatic Hydrops Reversal following Acetazolamide Therapy: Demonstration with Delayed Intravenous Contrast-Enhanced 3D-FLAIR MRI. AB - Endolymphatic hydrops, the primary pathologic alteration in Meniere disease, can be visualized by using delayed intravenous contrast-enhanced 3D-FLAIR MR imaging. It is not known whether MR imaging-demonstrable changes of hydrops fluctuate with disease activity or are fixed. We describe the results of baseline and posttreatment MR imaging studies in a group of subjects with Meniere disease with hydrops who were treated with acetazolamide. Seven subjects with untreated Meniere disease with MR imaging evidence of hydrops had repeat MR imaging during acetazolamide treatment. Symptoms and imaging findings were assessed at each time point. Five subjects showed symptom improvement, of whom 3 had improvement or resolution of hydrops. One subject had recurrent symptoms with recurrent hydrops after discontinuing therapy. Two had unchanged hydrops despite symptom improvement. Subjects with unchanged symptoms had unchanged hydrops. Hydrops reversal may be seen with acetazolamide treatment in Meniere disease. MR imaging may provide an additional biomarker of disease. PMID- 26381562 TI - Responses of the Human Brain to Mild Dehydration and Rehydration Explored In Vivo by 1H-MR Imaging and Spectroscopy. AB - BACKGROUND AND PURPOSE: As yet, there are no in vivo data on tissue water changes and associated morphometric changes involved in the osmo-adaptation of normal brains. Our aim was to evaluate osmoadaptive responses of the healthy human brain to osmotic challenges of de- and rehydration by serial measurements of brain volume, tissue fluid, and metabolites. MATERIALS AND METHODS: Serial T1-weighted and (1)H-MR spectroscopy data were acquired in 15 healthy individuals at normohydration, on 12 hours of dehydration, and during 1 hour of oral rehydration. Osmotic challenges were monitored by serum measures, including osmolality and hematocrit. MR imaging data were analyzed by using FreeSurfer and LCModel. RESULTS: On dehydration, serum osmolality increased by 0.67% and brain tissue fluid decreased by 1.63%, on average. MR imaging morphometry demonstrated corresponding decreases of cortical thickness and volumes of the whole brain, cortex, white matter, and hypothalamus/thalamus. These changes reversed during rehydration. Continuous fluid ingestion of 1 L of water for 1 hour within the scanner lowered serum osmolality by 0.96% and increased brain tissue fluid by 0.43%, on average. Concomitantly, cortical thickness and volumes of the whole brain, cortex, white matter, and hypothalamus/thalamus increased. Changes in brain tissue fluid were related to volume changes of the whole brain, the white matter, and hypothalamus/thalamus. Only volume changes of the hypothalamus/thalamus significantly correlated with serum osmolality. CONCLUSIONS: This is the first study simultaneously evaluating changes in brain tissue fluid, metabolites, volume, and cortical thickness. Our results reflect cellular volume regulatory mechanisms at a macroscopic level and emphasize that it is essential to control for hydration levels in studies on brain morphometry and metabolism in order to avoid confounding the findings. PMID- 26381563 TI - Predicting High-Flow Spinal CSF Leaks in Spontaneous Intracranial Hypotension Using a Spinal MRI-Based Algorithm: Have Repeat CT Myelograms Been Reduced? AB - BACKGROUND AND PURPOSE: We adopted an imaging algorithm in 2011 in which extradural fluid on spinal MR imaging directs dynamic CT myelography. We assessed algorithm compliance and its effectiveness in reducing repeat or unnecessary dynamic CT myelograms. MATERIALS AND METHODS: CT myelograms for CSF leaks from January 2011 to September 2014 were reviewed. Patients with iatrogenic leaks, traumatic brachial plexus injuries, or prior CT myelography within 2 years were excluded. Completion and results of spinal MR imaging, CT myelographic technique, and the need for repeat CT myelography or unnecessary dynamic CT myelograms were recorded. RESULTS: The algorithm was followed in 102 (79%) of 129 patients. No extradural fluid was detected in 75 (74%), of whom 70 (93%) had no leak, 4 (5%) had a slow leak, and 1 (1%) had a fast leak. Extradural fluid was detected in 27 (26%): 24 (89%) fast leaks, 1 (4%) slow leak, and 2 (7%) with no leaks. When the algorithm was followed, 1 (1%) required repeat CT myelography and 3 (3%) had unnecessary dynamic CT myelograms. The algorithm was breached in 27 (21%) cases, including no pre-CT myelogram MR imaging in 11 (41%), performing conventional CT myelography when extradural fluid was present in 13 (48%), and performing dynamic CT myelography when extradural fluid was absent in 3 (11%). Algorithm breaches resulted in 4 (15%) repeat CT myelograms and 3 (12%) unnecessary dynamic CT myelograms, both higher than with algorithm compliance. CONCLUSIONS: Using spinal MR imaging to direct CT myelography resulted in significant reduction in repeat CT myelograms to localize fast leaks with minimal unnecessary dynamic CT myelograms. PMID- 26381564 TI - Presurgical Assessment of the Sensorimotor Cortex Using Resting-State fMRI. AB - BACKGROUND AND PURPOSE: The functional characterization of the motor cortex is an important issue in the presurgical evaluation of brain lesions. fMRI noninvasively identifies motor areas while patients are asked to move different body parts. This task-based approach has some drawbacks in clinical settings: long scanning times and exclusion of patients with severe functional or neurologic disabilities and children. Resting-state fMRI can avoid these difficulties because patients do not perform any goal-directed tasks. MATERIALS AND METHODS: Nineteen patients with diverse brain pathologies were prospectively evaluated by using task-based and resting-state fMRI to localize sensorimotor function. Independent component analyses were performed to generate spatial independent components reflecting functional brain networks or noise. Three radiologists identified the motor components and 3 portions of the motor cortex corresponding to the hand, foot, and face representations. Selected motor independent components were compared with task-based fMRI activation maps resulting from movements of the corresponding body parts. RESULTS: The motor cortex was successfully and consistently identified by using resting-state fMRI by the 3 radiologists for all patients. When they subdivided the motor cortex into 3 segments, the sensitivities of resting-state and task-based fMRI were comparable. Moreover, we report a good spatial correspondence with the task-based fMRI activity estimates. CONCLUSIONS: Resting-state fMRI can reliably image sensorimotor function in a clinical preoperative routine. It is a promising opportunity for presurgical localization of sensorimotor function and has the potential to benefit a large number of patients affected by a wide range of pathologies. PMID- 26381565 TI - Comparison of the Effect of Vessel Size Imaging and Cerebral Blood Volume Derived from Perfusion MR Imaging on Glioma Grading. AB - BACKGROUND AND PURPOSE: Vascular proliferation is a major criterion for grading gliomas on the basis of histology. Relative cerebral blood volume can provide pathophysiologic information about glioma grading. Vessel size imaging, in some animals, can be used to estimate the microvascular caliber of a glioma, but its clinical use remains unclear. Herein, we aimed to compare the predictive power of relative cerebral blood volume and vessel size imaging in glioma grading, with grading based on histology. MATERIALS AND METHODS: Seventy patients with glioma participated in the study; 30 patients underwent MR perfusion imaging with a spin echo sequence and vessel size imaging with a gradient-echo and spin-echo sequence successively at 24-hour intervals before surgery. We analyzed the vessel size imaging values and relative cerebral blood volume of differently graded gliomas. The microvessel parameters were histologically evaluated and compared with those on MR imaging. The cutoff values of vessel size imaging and relative cerebral blood volume obtained from receiver operating characteristic curve analyses were used to predict glioma grading in another 40 patients. RESULTS: Vessel size imaging values and relative cerebral blood volume were both increased in high grade gliomas compared with low-grade gliomas (P < .01). Moreover, vessel size imaging values had higher specificity and sensitivity in differentiating high grade from low-grade gliomas compared with relative cerebral blood volume. In addition, a significant correlation was observed between vessel size imaging values and microvessel diameters (r > 0.8, P < .05) and between relative cerebral blood volume and microvessel area (r = 0.6579, P < .05). Most important, the use of vessel size imaging cutoff values to predict glioma grading was more accurate (100%) than use of relative cerebral blood volume (85%) values. CONCLUSIONS: Vessel size imaging can provide more accurate information on glioma grading and may serve as an effective biomarker for the prognosis of patients with gliomas. PMID- 26381566 TI - Recognizing Autoimmune-Mediated Encephalitis in the Differential Diagnosis of Limbic Disorders. AB - Limbic encephalitis is far more common than previously thought. It is not always associated with cancer, and it is potentially treatable. Autoantibodies against various neuronal cell antigens may arise independently or in association with cancer and cause autoimmune damage to the limbic system. Neuroimaging plays a key role in the management of patients with suspected limbic encephalitis by supporting diagnosis and excluding differential possibilities. This article describes the main types of autoimmune limbic encephalitis and its mimic disorders, and emphasizes their major imaging features. PMID- 26381567 TI - Determination of alkylphenols in water samples using liquid chromatography-tandem mass spectrometry after pre-column derivatization with dansyl chloride. AB - The present study describes an effect of reaction condition of pre-column derivatization of alkylphenols (APs): bisphenol A (BPA), 4-tert-octylphenol (4-t OP), 4-octylphenol (4-OP), 4-n-nonylphenol (4-n-NP), and isomers of 4-nonylphenol (iso-NP) with 5-(dimethylamino) naphthalene-1-sulfonyl chloride (dansyl chloride, DNSC) on their LC-ESI-MS/MS determination in water samples. Chemical derivatization improves the sensitivity and selectivity of LC-MS/MS analysis. In principle, alkylphenols can be analyzed by LC-MS/MS without derivatization. However, pre-column derivatization of APs increases the sensitivity up to 1000 times in comparison with the analysis of underivatized alkylphenols. Reaction conditions affecting formation of the DNSC-derivatives, such as various solvent, reaction temperature, reaction time, DNSC concentration and pH values were tested. The most suitable conditions, in terms of achieving a high sensitivity, resulting from this study are: acetonitrile as reaction solvent, 60 min as reaction time, 60 degrees C as reaction temperature, pH values 10.5, 0.5 mg mL( 1) as DNSC concentration. Calibration curves are linear at least in the range of 1-1000 ng mL(-1), limits of detection (LOD) and limits of quantification (LOQ) ranging from 0.02 to 0.25 pg/injection and from 0.08 to 0.83 pg/injection, respectively. The improved procedure was successfully applied for the analysis of APs and BPA in real water samples. The median concentration of BPA and iso-NP obtained in bottled waters was 4.7 ng L(-1) and 33.5 ng L(-1), respectively. The median concentration of 4-t-OP was 1.3 ng L(-1.) PMID- 26381568 TI - Analysis of diarrhetic shellfish poisoning toxins and pectenotoxin-2 in the bottlenose dolphin (Tursiops truncatus) by liquid chromatography-tandem mass spectrometry. AB - Toxins produced by harmful algae are associated with detrimental health effects and mass mortalities of marine mammals. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is generally used to confirm the presence of algal toxins in marine mammals. Sample preparation and LC-MS/MS methods for the determination of three diarrhetic shellfish poisoning (DSP) toxins (okadaic acid, OA; dinophysistoxin-1, DTX1; dinophysistoxin-2, DTX2) and pectenotoxin-2 (PTX2) in bottlenose dolphin (Tursiops truncatus) urine and tissue samples were evaluated using spike-and-recovery tests. Sample clean-up with either reversed-phase silica or polymeric solid-phase extraction (SPE) reduced interference of sample matrices and improved toxin recoveries, with polymeric SPE showing higher sample loading capacity. LC separation on Xbridge C18 columns using acetonitrile/water gradient elutions with ammonia as the additive was chosen for its high detectivity and sensitivity in the MS detection of DSP toxins in negative ion mode. The retention times of OA, DTX1, and DTX2, separated as negative ions, increased with LC column temperature while the retention time of PTX2, separated as the neutral molecule, was weakly affected. At the same column temperature, retention times of OA, DTX1, and DTX2 gradually increased as the mobile phases aged while the retention time of PTX2 remained unchanged; higher column temperatures resulted in a greater increase in the retention time of each DSP toxin with mobile phase aging. Average recoveries of the 4 toxins in bottlenose dolphin samples ranged from 80% to 130% with relative standard deviations of less than 15% using the LC mobile phases prepared within one week at a column temperature of 30 degrees C or 40 degrees C. The preferred column temperature was 30 degrees C, as the retention times of DSP toxins were less affected by mobile phase aging at this temperature. The limit of detection of each toxin analyzed in bottlenose dolphin samples was 2.8 ng/g or less in tissue samples and 0.7 ng/ml or less in urine. PMID- 26381569 TI - Evolution in miniaturized column liquid chromatography instrumentation and applications: An overview. AB - The purpose of this article is to underline the miniaturized LC instrumental system and describe the evolution of commercially available systems by discussing their advantages and drawbacks. Nowadays, there are already many miniaturized LC systems available with a great variety of pump design, interface and detectors as well as efficient columns technologies and reduced connections devices. The solvent delivery systems are able to drive the mobile phase without flow splitters and promote gradient elution using either dual piston reciprocating or syringe-type pumps. The mass spectrometry as detection system is the most widely used detection system; among many alternative ionization sources direct-EI LC-MS is a promising alternative to APCI. In addition, capillary columns are now available showing many possibilities of stationary phases, inner diameters and hardware materials. This review provides a discussion about miniaturized LC demonstrating fundamentals and instrumentals' aspects of the commercially available miniaturized LC instrumental system mainly nano and micro LC formats. This review also covers the recent developments and trends in instrumentation, capillary and nano columns, and several applications of this very important and promising field. PMID- 26381570 TI - Total zinc quantification by inductively coupled plasma-mass spectrometry and its speciation by size exclusion chromatography-inductively coupled plasma-mass spectrometry in human milk and commercial formulas: Importance in infant nutrition. AB - This paper summarises results of zinc content and its speciation in human milk from mothers of preterm and full-term infants at different stages of lactation and from synthetic formula milks. Human milk samples (colostrum, 7th, 14th, and 28th day after delivery) from Spanish and Brazilian mothers of preterm and full term infants (and also formula milks) were collected. After adequate treatment of the sample, total Zn was determined, while speciation analysis of the Zn was accomplished by size exclusion chromatography coupled online with the ICP-MS. It is observed that total zinc content in human milk decreases continuously during the first month of lactation, both for preterm and full term gestations. All infant formulas analysed for total Zn were within the currently legislated levels. For Zn speciation analysis, there were no differences between preterm and full term human milk samples. Moreover Zn species elute mainly associated with immunoglobulins and citrate in human milk whey. Interestingly the speciation in formula milk whey turned out to be completely different as the observed Zn(2+) was bound almost exclusively to low molecular weight ligands (citrate) and only comparatively very low amounts of the metal appeared to be associated with higher mass biomolecules (e.g. proteins). PMID- 26381572 TI - Oral surgery in the European Union: challenges of diversity in training and practice. AB - INTRODUCTION: At the crossroads of medicine and dentistry, oral surgery with orthodontics are the only recognised dental specialties by the European Union. The goal of our study is to evaluate the current state of oral surgery in Europe from its teaching to its practice, the hypothesis being that a notable diversity persists despite European Union harmonisation process. MATERIALS AND METHODS: To understand the impact of this diversity applied to European Union freedom of movement and its ethical implications for the practice of oral surgery, English and French questionnaires were sent by email to universities and organisations delivering authorisation to practise in France, Germany, Spain, Sweden and United Kingdom chosen based upon inclusion and exclusion criteria. An analysis of documents on these organisations' official websites was also conducted. Demographic information was obtained from the aforementioned organisations. RESULTS: The profile of practising oral surgeons is different dependent on the country. The university and hospital trainings conform to European recommendations and span 3-4 years. European Board certification is not required. Continuing education is mandatory only in France, Germany and United Kingdom. As for curricula and scope of practice, no consensus can be derived. DISCUSSION: There is potential conflict of interest between European Union principles of freedom of movement and protection of all citizens, as member countries do not uniformly apply Directives and recommendations. A new survey of all European Union oral surgery programmes as well as organisations delivering authorisation to practise is necessary to implement across the board harmonisation of training and practice to insure patient safety in light of the migration of European Union practitioners. PMID- 26381571 TI - Analysis of drug-protein binding using on-line immunoextraction and high performance affinity microcolumns: Studies with normal and glycated human serum albumin. AB - A method combining on-line immunoextraction microcolumns with high-performance affinity chromatography (HPAC) was developed and tested for use in examining drug protein interactions with normal or modified proteins. Normal human serum albumin (HSA) and glycated HSA were used as model proteins for this work. High performance immunoextraction microcolumns with sizes of 1.0-2.0 cm * 2.1mm i.d. and containing anti-HSA polyclonal antibodies were developed and tested for their ability to bind normal HSA or glycated HSA. These microcolumns were able to extract up to 82-93% for either type of protein at 0.05-0.10 mL/min and had a binding capacity of 0.34-0.42 nmol HSA for a 1.0 cm * 2.1mm i.d. microcolumn. The immunoextraction microcolumns and their adsorbed proteins were tested for use in various approaches for drug binding studies. Frontal analysis was used with the adsorbed HSA/glycated HSA to measure the overall affinities of these proteins for the drugs warfarin and gliclazide, giving comparable values to those obtained previously using similar protein preparations that had been covalently immobilized within HPAC columns. Zonal elution competition studies with gliclazide were next performed to examine the specific interactions of this drug at Sudlow sites I and II of the adsorbed proteins. These results were also comparable to those noted in prior work with covalently immobilized samples of normal HSA or glycated HSA. These experiments indicated that drug-protein binding studies can be carried out by using on-line immunoextraction microcolumns with HPAC. The same method could be used in the future with clinical samples and other drugs or proteins of interest in pharmaceutical studies or biomedical research. PMID- 26381573 TI - Impact of classical risk factors of type 2 diabetes among Asian Indian, Chinese and Japanese populations. AB - AIMS: This review investigated the population impact of major modifiable type 2 diabetes (T2D) risk factors, with special focus on native Asian Indians, to estimate population attributable risks (PARs) and compare them with estimates from Chinese and Japanese populations. METHODS: Information was obtained on risk factors in 21,041 Asian Indian, 17,774 Chinese and 17,986 Japanese populations from multiple, large, cross-sectional studies (the DECODA project) of T2D. Crude and adjusted PARs were estimated for the major T2D risk factors. RESULTS: Age had the highest crude and adjusted PARs among Asian Indians and Chinese in contrast to waist-hip ratio among Japanese. After adjusting for age, the PAR for body mass index (BMI) in Asian Indians (41.4% [95% CI: 37.2%; 45.4%]) was second only to triglycerides (46.4% [95% CI: 39.5%; 52.8%]) compared with 35.8% [95% CI: 29.9%; 41.4%] in Japanese and 38.4% [95% CI: 33.5%; 43.2%] in Chinese people. The PAR for BMI adjusted for age, LDL and triglycerides (39.7% [95% CI: 31.6%; 47.2%]) was higher than for any other factor in Asian Indians, and was much higher than in the Chinese (16.8% [95% CI: 3.0%; 30.9%]) and Japanese (30.4% [95% CI: 17.5%; 42.2%]) populations. CONCLUSION: This review provides estimates of the association between major risk factors and prevalences of T2D among Asian populations by examining their PARs from large population-based samples. From a public-health point of view, the importance of BMI in Asian Indians is especially highlighted in comparison to the other Asian populations. Given these results and other recent findings on the causality link between BMI and T2D, it can be postulated that obesity may be involved in the aetiology of T2D through interaction with ethnic-specific genetic factors, although ethnicity itself is not a direct risk factor for T2D as people of all ethnic backgrounds develop diabetes. PMID- 26381574 TI - CD4 T-cell function assay using Cylex ImmuKnow and lymphocyte subset recovery following allogeneic hematopoietic stem cell transplantation. AB - We analyzed CD4 T-lymphocytes ATP levels along with lymphocyte subsets in 160 samples from 111 post-allogeneic hematopoietic stem cell transplantation (alloHSCT) patients. In patients with stable status, ImmuKnow levels changed over time and the 6-month post-alloHSCT levels were significantly higher than those tested within 6 months post-alloHSCT (P < 0.001). Although, ImmuKnow levels for acute graft-versus-host disease (GVHD) or infection episodes were not significantly different compared to those for stable alloHSCT, the levels were correlated with specific lymphocyte subpopulations at different times; the results within 6 months post-alloHSCT showed low positive correlation with natural killer cell count (r = 0.328) (P < 0.05) and the values tested later than 6 months post-alloHSCT were positively correlated with CD4 T cell count (r = 0.425) (P < 0.05). Two patients who developed acute GVHD and two who experienced an infection episode showed increased ImmuKnow levels in sequential tests. The combined test of ImmuKnow levels and lymphocyte subsets may be helpful for immune monitoring following alloHSCT. PMID- 26381575 TI - Knockdown of either filaggrin or loricrin increases the productions of interleukin (IL)-1alpha, IL-8, IL-18 and granulocyte macrophage colony stimulating factor in stratified human keratinocytes. PMID- 26381577 TI - Effect of inflammation stimulation on energy and nutrient utilization in piglets selected for low and high residual feed intake. AB - Selection of animals for improved feed efficiency can affect sustainability of animal production because the most efficient animals may face difficulties coping with challenges. The objective of this study was to determine the effects of an inflammatory challenge (using an intravenous injection of complete Freund's adjuvant - CFA) in piglets from two lines of pigs divergently selected during the fattening period for a low (RFI-) or a high (RFI+) residual feed intake (RFI; difference between actual feed intake and theoretical feed requirements). Nitrogen and energy balances (including heat production - HP - and its components: activity-related HP - AHP, thermic effect of feeding, and resting HP) were measured individually in thirteen 20-kg BW castrated male piglets (six and seven from RFI+ and RFI- line, respectively) fed at the same level (1.72 MJ ME/kg BW0.60 per day) from 3 days before to 3 days after CFA injection. Dynamics of dietary U-13C-glucose oxidation were estimated from measurements of 13CO2 production on the day before and 3 days after the CFA injection. Oxidation of dietary nutrients and lipogenesis were calculated based on HP and O2 consumption and CO2 production. The data were analyzed as repeated measurements within piglets in a mixed model. Before CFA injection, RFI- piglets had a lower resting energy expenditure than RFI+ piglets, which tended to increase energy retention because of a higher energy retention as fat. The CFA injection did not affect feed intake from the day following CFA injection onwards but it increased energy retention (P=0.04). Time to recover 50% of 13C from dietary glucose as expired 13CO2 was higher in RFI+ piglets before inducing inflammation but decreased after to the level of RFI- piglets (P<0.01). Oxidation of U-13C-glucose tended to slightly increased in RFI- piglets and to decreased in RFI+ piglets (P=0.10) because of CFA. Additionally, RFI- piglets had a lower respiratory quotient during the 1st day following the CFA injection whereas RFI+ piglets tended to have a higher respiratory quotient. In conclusion, selection for RFI during the fattening period also affected the energy metabolism of pigs during earlier stages of growth. The effects of CFA injection were moderated in both lines but the most efficient animals (RFI-) exhibited a marked re-orientation of nutrients only during the 1st day after CFA, and seemed to recover thereafter, whereas the less efficient piglets expressed a more prolonged alteration of their metabolism. PMID- 26381576 TI - Tryptophan metabolism, disposition and utilization in pregnancy. AB - Tryptophan (Trp) requirements in pregnancy are several-fold: (1) the need for increased protein synthesis by mother and for fetal growth and development; (2) serotonin (5-HT) for signalling pathways; (3) kynurenic acid (KA) for neuronal protection; (4) quinolinic acid (QA) for NAD(+) synthesis (5) other kynurenines (Ks) for suppressing fetal rejection. These goals could not be achieved if maternal plasma [Trp] is depleted. Although plasma total (free + albumin-bound) Trp is decreased in pregnancy, free Trp is elevated. The above requirements are best expressed in terms of a Trp utilization concept. Briefly, Trp is utilized as follows: (1) In early and mid-pregnancy, emphasis is on increased maternal Trp availability to meet the demand for protein synthesis and fetal development, most probably mediated by maternal liver Trp 2,3-dioxygenase (TDO) inhibition by progesterone and oestrogens. (2) In mid- and late pregnancy, Trp availability is maintained and enhanced by the release of albumin-bound Trp by albumin depletion and non-esterified fatty acid (NEFA) elevation, leading to increased flux of Trp down the K pathway to elevate immunosuppressive Ks. An excessive release of free Trp could undermine pregnancy by abolishing T-cell suppression by Ks. Detailed assessment of parameters of Trp metabolism and disposition and related measures (free and total Trp, albumin, NEFA, K and its metabolites and pro- and anti inflammatory cytokines in maternal blood and, where appropriate, placental and fetal material) in normal and abnormal pregnancies may establish missing gaps in our knowledge of the Trp status in pregnancy and help identify appropriate intervention strategies. PMID- 26381578 TI - pH-Cleavable Nucleoside Lipids: A New Paradigm for Controlling the Stability of Lipid-Based Delivery Systems. AB - Lipid-based delivery systems are an established technology with considerable clinical acceptance and several applications in human. Herein, we report the design, synthesis and evaluation of novel orthoester nucleoside lipids (ONLs) for the modulation of liposome stability. The ONLs contain head groups with 3' orthoester nucleoside derivatives featuring positive or negative charges. The insertion of the orthoester function in the NL structures allows the formation of pH-sensitive liposomes. ONL-based liposomes can be hydrolyzed to provide nontoxic products, including nucleoside derivatives and hexadecanol. To allow the release to be tunable at different hydrolysis rates, the charge of the polar head structure is modulated, and the head group can be released at a biologically relevant pH. Crucially, when ONLs are mixed with natural phosphocholine lipids (PC), the resultant liposome evolves toward the formation of a hexadecanol/PC lamellar system. Biological evaluation shows that stable nucleic acid lipid particles (SNALPs) formulated with ONLs and siRNAs can effectively enter into tumor cells and release their nucleic acid payload in response to an intracellular acidic environment. This results in a much higher antitumor activity than conventional SNALPs. The ability to use pH-cleavable nucleolipids to control the stability of lipid-based delivery systems represents a promising approach for the intracellular delivery of drug cargos. PMID- 26381579 TI - Effect of exposure to extremely low frequency magnetic fields on melatonin levels in calves is seasonally dependent. AB - The question of health effects of extremely low frequency (50/60 Hz) magnetic fields (ELFMF) has been widely discussed, but the mechanisms of interaction of these fields with biological systems for intensities relevant to human and animal exposure are still under question. The melatonin (MLT) hypothesis suggests that exposure to ELFMF might decrease MLT production thereby promoting cancerogenesis. So far, most studies of MLT secretion under exposure to ELFMF reported negative or inconsistent results. Here, we measured salivary MLT in 1-2 months old cattle calves exposed to 50 Hz-MF in the hundreds of nT-range. We found an inhibitory effect of the ELFMF upon MLT secretion in winter (in accordance with the MLT hypothesis). In contrast, in summer, MLT concentration was increased by ELFMF exposure (contrary to the MLT hypothesis). The inhibitory effect in winter was much stronger than the positive effect in summer. We hypothesize that this season dependent effect upon MLT synthesis might by mediated by an effect of ELFMF upon the serotonin metabolism and conclude that future tests of ELFMF effects should also measure serotonin levels and consider association with the seasonal effects (photoperiod or temperature) during the exposure. PMID- 26381580 TI - An intrinsic timer specifies distal structures of the vertebrate limb. AB - How the positional values along the proximo-distal axis (stylopod-zeugopod autopod) of the limb are specified is intensely debated. Early work suggested that cells intrinsically change their proximo-distal positional values by measuring time. Recently, however, it is suggested that instructive extrinsic signals from the trunk and apical ectodermal ridge specify the stylopod and zeugopod/autopod, respectively. Here, we show that the zeugopod and autopod are specified by an intrinsic timing mechanism. By grafting green fluorescent protein expressing cells from early to late chick wing buds, we demonstrate that distal mesenchyme cells intrinsically time Hoxa13 expression, cell cycle parameters and the duration of the overlying apical ectodermal ridge. In addition, we reveal that cell affinities intrinsically change in the distal mesenchyme, which we suggest results in a gradient of positional values along the proximo-distal axis. We propose a complete model in which a switch from extrinsic signalling to intrinsic timing patterns the vertebrate limb. PMID- 26381581 TI - Is Online Learning a Viable Training Option for Teaching Sexual Assault Forensic Examiners? AB - This study assessed knowledge attainment of healthcare professionals who participated in a nationwide sexual assault forensic examiner training program developed by the International Association of Forensic Nursing. A comprehensive curriculum was divided into 12 modules that students accessed through an online learning management system. Using a one-group pretest-posttest design, we assessed students' knowledge attainment for all 12 online modules. The results showed that the mean posttest scores were significantly greater than the mean pretest scores for all 12 online modules. On over 40% of the modules, the students exhibited at least a 25% knowledge gain. This study also examined the predictors of knowledge attainment. Using a multiple linear regression model, we found that knowledge attainment was positively associated with a reliable Internet connection, students who were drawn to the training because it was of no cost to them, and those students with higher levels of motivation. By contrast, lower knowledge gains were significantly related to students who reported more work/personal barriers and those who were drawn to sexual assault forensic examiner practice because they, or someone close to them, have personal experience with sexual assault. PMID- 26381582 TI - Forced Sex and Sexual Consent Among College Women. AB - INTRODUCTION: Female college students, aged 18-25 years, are at high risk for sexual violence compared with women of other age groups. Lack of clear consent is a preceding and defining component of forced sex and sexual violence. This study explored the association between sexual consent awareness, attitudes, and beliefs and a history of forced sex among a sample of college women. In addition, the level of alcohol use among this group was examined. METHODS: A cross-sectional electronic survey was sent to approximately 5900 female students enrolled at a large public university in the northeastern United States. Sexual consent was measured with the Sexual Consent Scale-Revised, and alcohol use was measured with the Alcohol Use Disorders Identification Test-Consumption Items. Logistic regression models were used to examine the differences in sexual consent scores based on a history of forced sex. RESULTS: The final sample included 925 students. Twenty-two percent of participants reported a history of forced sex; more than half (59%) reported alcohol use before sexual activity. Women with greater awareness of sexual consent were significantly more likely to have a history of forced sex. Women who utilize more nonverbal, indirect approaches to communicating sexual consent were significantly less likely to have a history of forced sex compared with women with no history of forced sex. DISCUSSION: These findings highlight high rates of forced sex and alcohol use in a sample of college women and explicate sexual consent awareness and communication behaviors associated with a history of forced sex. PMID- 26381583 TI - A size-dependent structural evolution of ZnS nanoparticles. AB - Recently, ZnS quantum dots have attracted a lot of attention since they can be a suitable alternative for cadmium-based quantum dots, which are known to be highly carcinogenic for living systems. However, the structural stability of nanocrystalline ZnS seems to be a challenging issue since ZnS nanoparticles have the potential to undergo uncontrolled structural change at room temperature. Using the molecular dynamics technique, we have studied the structural evolution of 1 to 5 nm freestanding ZnS nanoparticles with zinc-blende and wurtzite crystal structures. Simulation results revealed that relaxed configurations of ZnS nanoparticles larger than 3 nm consist of three regions: a) a crystalline core, b) a distorted network of 4-coordinated atoms environing the crystalline core, and c) a surface structure made entirely of 3-coordinated atoms. Decreasing the size of ZnS nanoparticle to 2 nm will cause the crystalline core to disappear. Further reducing the size will cause all of the atoms to become 3-coordinated. Dipole moments of zinc-blende and wurtzite nanoparticles are in the same range when the nanoparticles are smaller than 3 nm. Increasing the size makes dipole moments converge to the bulk values. This makes zinc-blende and wurtzite nanoparticles less and more polar, respectively. PMID- 26381584 TI - Erratum: Functional BCL-2 regulatory genetic variants contribute to susceptibility of esophageal squamous cell carcinoma. PMID- 26381585 TI - Metatranscriptomic insights into polyphosphate metabolism in marine sediments. AB - Microorganisms can influence inorganic phosphate (Pi) in pore waters, and thus the saturation state of phosphatic minerals, by accumulating and hydrolyzing intracellular polyphosphate (poly-P). Here we used comparative metatranscriptomics to explore microbial poly-P utilization in marine sediments. Sulfidic marine sediments from methane seeps near Barbados and from the Santa Barbara Basin (SBB) oxygen minimum zone were incubated under oxic and anoxic sulfidic conditions. Pi was sequestered under oxic conditions and liberated under anoxic conditions. Transcripts homologous to poly-P kinase type 2 (ppk2) were 6 22 * more abundant in metatranscriptomes from the anoxic incubations, suggesting that reversible poly-P degradation by Ppk2 may be an important metabolic response to anoxia by marine microorganisms. Overall, diverse taxa differentially expressed homologues of genes for poly-P degradation (ppk2 and exopolyphosphatase) under different incubation conditions. Sulfur-oxidizing microorganisms appeared to preferentially express genes for poly-P degradation under anoxic conditions, which may impact phosphorus cycling in a wide range of oxygen-depleted marine settings. PMID- 26381586 TI - Assignment of photoelectron spectra of silatranes: first ionization energies and the nature of the dative Si<-N contact. AB - The problematic experimental photoelectron spectra of fluoro- and ethoxy silatranes, XSi[OCH2CH2]3N (X = F and OEt), were assigned using theoretical spectra obtained by combining the OVGF//CCSD vertical ionization energies with the vibrational widths of the electronic transitions (linear vibronic coupling formalism, LVC). Taking into account the overlapping of the silatrane bands with the bands of probable impurities, bicyclic amines, (OH)XSi(OCH2CH2)2NCH2CH2OH, allowed us to reliably determine the position of the low-energy bands (at ~9.7 eV for F- and at ~9.2 eV for EtO-silatrane) associated with the ionization from a nitrogen lone pair level. For XSi[OCH2CH2]3N (X = F, H, OEt, Me), the correlation between the first vertical ionization energies, VIEs1, and the geometrical, electronic and orbital characteristics of the Si<-N bonding was found. Its analysis suggests that the Si<-N coordination in silatranes is orbital-controlled rather than charge-controlled. PMID- 26381587 TI - Metal ions modulate the conformation and stability of a G-quadruplex with or without a small-molecule ligand. AB - Small-molecule ligands for stabilizing the G-quadruplex in telomeres are promising chemotherapeutic agents. Despite extensive research, few G-quadruplex stabilizing ligands have been clinically approved to date. We hypothesized that metal ions may be able to interfere with the ligand-mediated stabilization of the G-quadruplex. Here we found that several metal ions could interfere with the Na(+)-induced G-quadruplex conformation even in the presence of a ligand. The destabilizing effects of metal ions may not be negligible as most of them are essential elements in organisms. In contrast, Ba(2+) was found to be a potent stabilizing cation, which could compete with other destabilizing cations to modulate the stability of the G-quadruplex. Moreover, the destabilizing effects of divalent or trivalent cations were considerably inhibited when a metal chelator was used. These data suggested that the unfavorable effects of destabilizing cations must be minimized for enhancing the ligand-mediated stabilization of the G-quadruplex. PMID- 26381588 TI - Exposure to vehicular traffic is associated to a higher risk of hospitalization for bronchiolitis during the first year of life. AB - BACKGROUND: The most common cause of hospitalization for children younger than age one is bronchiolitis. Several prenatal and environmental risk factors may affect the incidence of hospitalization for bronchiolitis. The aim of this study was to investigate the relation between exposure to vehicular traffic and the incidence of hospitalization for bronchiolitis in children during their first year of life in Italy. METHODS: A multicenter prospective birth cohort study, where equal numbers of newborns of 33-34, 35-37 and >=38 wGA were recruited at birth (1814 children) in 30 Italian neonatology units. Two interviewer administered questionnaires were used to collect data. The first interview was carried out at the end of the Italian epidemic season. The second interview was carried out when the child was one year old. Data on possible prenatal, perinatal, and postnatal/environmental risk factors and on vehicular traffic density in the zone of residence were collected. On each interview, parents were also asked about any hospitalizations of the child. The outcome measure was the hospitalization for bronchiolitis (International Health Service ICD-9 code 466). RESULTS: Univariate analysis demonstrated that exposure to air pollution due to vehicular traffic, was significantly associated with an increased risk of hospitalization for bronchiolitis. The adjusted risk from logistic regression model confirmed that children exposed to air pollution due to vehicular traffic were at increased risk of hospitalization for bronchiolitis. CONCLUSIONS: Exposure to air pollution due to vehicular traffic may increase the risk of hospitalization for bronchiolitis in the first year of life. PMID- 26381589 TI - Wrapping of nanoparticles by the cell membrane: the role of interactions between the nanoparticles. AB - A fundamental understanding of the interactions between nanoparticles (NPs) and the cell membrane is essential to improve the performance of the NP-based biomedical applications and assess the potential toxicity of NPs. Despite the great progress in understanding the interaction between individual NP and the membrane, little is known about the interaction between multiple NPs and the membrane. In this work, we investigate the wrapping of two parallel elongated NPs by the membrane, taking the NP-NP electrostatic interaction and van der Waals (vdW) interaction into consideration. Three types of NPs, namely the rigid NPs with circular and elliptic cross-sections and the deformable NPs, are systematically investigated. The results show that the electrostatic interaction would enhance the tendency of the independent wrapping and inhibit the rotation of the elongated and equally charged NPs with elliptic cross-sections. Under the vdW interaction, the competition of the NP-NP adhesion and the membrane elastic energies with the NP-membrane adhesion energy leads the NPs to be wrapped cooperatively or independently. For the system with elongated NPs with elliptic cross-sections, the NPs are more likely to be wrapped independently as the shapes become more anisotropic and the NPs would rotate to contact each other with the flat sides in the cooperative wrapping configuration. Moreover, the soft NPs are more likely to be wrapped cooperatively compared with the stiff NPs. These results may provide guidelines to control the internalization pathway of NPs and improve the efficiency of NP-based drug delivery systems. PMID- 26381590 TI - Regioselective Green Electrochemical Approach to the Synthesis of Nitroacetaminophen Derivatives. AB - A regioselective green synthesis of nitroacetaminophen derivatives was carried out by electrochemical oxidation of acetaminophen, N-(2-hydroxyphenyl)acetamide, and 1-(4-(4-hydroxyphenyl)piperazin-1-yl)ethanone in the presence of nitrite ion as a nucleophile. The present work has led to the development of a reagentless green and facile electrochemical method for the synthesis of some nitroacetaminophen derivatives. PMID- 26381591 TI - Direct Observation of Thermal Equilibrium of Excited Triplet States of 9,10 Phenanthrenequinone. A Time-Resolved Resonance Raman Study. AB - The photochemistry of aromatic ketones plays a key role in various physicochemical and biological processes, and solvent polarity can be used to tune their triplet state properties. Therefore, a comprehensive analysis of the conformational structure and the solvent polarity induced energy level reordering of the two lowest triplet states of 9,10-phenanthrenequinone (PQ) was carried out using nanosecond-time-resolved absorption (ns-TRA), time-resolved resonance Raman (TR(3)) spectroscopy, and time dependent-density functional theory (TD-DFT) studies. The ns-TRA of PQ in acetonitrile displays two bands in the visible range, and these two bands decay with similar lifetime at least at longer time scales (MUs). Interestingly, TR(3) spectra of these two bands indicate that the kinetics are different at shorter time scales (ns), while at longer time scales they followed the kinetics of ns-TRA spectra. Therefore, we report a real-time observation of the thermal equilibrium between the two lowest triplet excited states of PQ, assigned to npi* and pipi* of which the pipi* triplet state is formed first through intersystem crossing. Despite the fact that these two states are energetically close and have a similar conformational structure supported by TD-DFT studies, the slow internal conversion (~2 ns) between the T(2)(1(3)npi*) and T(1)(1(3)pipi*) triplet states indicates a barrier. Insights from the singlet excited states of PQ in protic solvents [ J. Chem. Phys. 2015 , 142 , 24305 ] suggest that the lowest npi* and pipi* triplet states should undergo hydrogen bond weakening and strengthening, respectively, relative to the ground state, and these mechanisms are substantiated by TD-DFT calculations. We also hypothesize that the different hydrogen bonding mechanisms exhibited by the two lowest singlet and triplet excited states of PQ could influence its ISC mechanism. PMID- 26381592 TI - Parent Telegraphic Speech Use and Spoken Language in Preschoolers With ASD. AB - PURPOSE: There is considerable controversy regarding whether to use telegraphic or grammatical input when speaking to young children with language delays, including children with autism spectrum disorder (ASD). This study examined telegraphic speech use in parents of preschoolers with ASD and associations with children's spoken language 1 year later. METHOD: Parent-child dyads (n = 55) participated when children were, on average, 3 (Time 1) and 4 years old (Time 2). The rate at which parents omitted obligatory determiners was derived from transcripts of parent-child play sessions; measures of children's spoken language were obtained from these same transcripts. RESULTS: Telegraphic speech use varied substantially across parents. Higher rates of parent determiner omissions at Time 1 were significantly associated with lower lexical diversity in children's spoken language at Time 2, even when controlling for children's baseline lexical diversity and nonverbal IQ. Findings from path analyses supported the directionality of effects assumed in our regression analyses, although these results should be interpreted with caution due to the limited sample size. CONCLUSIONS: Telegraphic input may have a negative impact on language development in young children with ASD. Future experimental research is needed to directly investigate how telegraphic input affects children's language learning and processing. PMID- 26381593 TI - Breech presentation is a risk factor for dysplasia of the femoral trochlea. AB - BACKGROUND AND PURPOSE: Instability of the patellofemoral joint is a common disorder in children and young adults. Although it has multifactorial causes, a shallow femoral trochlea is the single most important factor for instability. There is no consensus as to the etiology of trochlear dysplasia. We assessed whether the presentation of the fetus at birth could be a predisposing factor for trochlear dysplasia. SUBJECTS AND METHODS: We examined 348 knees in 174 newborns using ultrasonography, concentrating especially on the trochlea femoris. We measured the sulcus angle (SA) on a transverse scan. The way of fetal presentation at birth and standard parameters such as sex, gestational age, and length and weight at birth were registered. As breech presentation is a known risk factor for dysplasia of the hip, we also looked for an association between dysplasia of the femoral trochlea and dysplasia of the hips. RESULTS: The mean SA was 148 degrees . 17 knees in 14 children had an SA of >159 degrees , which was defined as the threshold value for dysplasia. The incidence of breech position in these children was 15-fold higher. Of the different groups of breech positions, a child in frank breech with the knees locked in extension had a 45-fold increased risk of having trochlear dysplasia. INTERPRETATION: For some newborns, a high sulcus angle can be found at birth, indicating that trochlear dysplasia can be found from birth. Breech presentation with knees extended appears to be a major risk factor for development of trochlear dysplasia. PMID- 26381594 TI - Central hemodynamics, vascular stiffness, and nocturia in patients with type 2 diabetes. AB - Recently, studies have shown that the presence of nocturia may not be a benign condition and related with systemic illness and mortality. Elevated blood pressure (BP) was another factor related with nocturia. Type 2 diabetes mellitus (T2DM) is also associated with nocturia. It is now clear that, apart from peripheral BP, central hemodynamic parameters are important for cardiovascular prognosis. However, no previous study in the literature examined the relationship between nocturia and central hemodynamic parameters in patients with T2DM. The current study was designed to examine these relationships. Nocturia was defined as two or more voids per night. Central hemodynamic parameters were assessed from ambulatory BP measurements. In addition to routine biochemistry, 24-h urine collection was performed to measure protein, albumin, and sodium excretion. 158 patients (52.3%) had T2DM and 144 (47.7%) did not have T2DM (control group). The presence of T2DM was independently related with nocturia. Both in whole group and in T2DM patients, most of the hemodynamic parameters are higher in patients with nocturia compared to patients without nocturia. Among patients with T2DM, nocturia was associated with augmentation index and pulse wave velocity. In conclusion, central hemodynamic parameters and markers of vascular stiffness may be related with nocturia in patients with T2DM. PMID- 26381595 TI - Differences in characteristics of mediolateral episiotomy in proffesionals at the same hospital. AB - OBJECTIVES: The objective of our study was to compare the theoretical concept of the accoucheur in our institution with regard to the characteristics of the mediolateral episiotomy (MLE), with a crowning head and after a delivery. METHODS: We devised two simple pictorial questionnaires (one with a crowning head and the other in rest after a delivery) in order to explore possible differences in clinical practice between the accoucheurs of our institution with respect to the MLE characteristics. RESULTS: With a crowning head, we found more acute angles when the age of accoucheurs was greater than 35 years old and more than 15 years of experience, but no with the perineum at rest. No difference was found between doctors and midwives, nor between males and females. 28.1% of accoucheurs indicated an acuter episiotomy angle with a crowning head. CONCLUSION: This study confirmed that the individual interpretation of MLE differed widely among professionals at the same hospital. These differences which have been shown could predispose women to a greater risk of anal sphincter injuries. For this reason, there is a need to standardize this practice, to make the technique more homogeneous, particularly in the context of future research into the risks and benefits of episiotomy with respect to major perineal trauma. PMID- 26381596 TI - Efficient Reprogramming of Human Fibroblasts and Blood-Derived Endothelial Progenitor Cells Using Nonmodified RNA for Reprogramming and Immune Evasion. AB - mRNA reprogramming results in the generation of genetically stable induced pluripotent stem (iPS) cells while avoiding the risks of genomic integration. Previously published mRNA reprogramming protocols have proven to be inconsistent and time-consuming and mainly restricted to fibroblasts, thereby demonstrating the need for a simple but reproducible protocol applicable to various cell types. So far there have been no published reports using mRNA to reprogram any cell type derived from human blood. Nonmodified synthetic mRNAs are immunogenic and activate cellular defense mechanisms, which can lead to cell death and inhibit mRNA translation upon repetitive transfection. Hence, to overcome RNA-related toxicity we combined nonmodified reprogramming mRNAs (OCT4, SOX2, KLF4, cMYC, NANOG, and LIN28 [OSKMNL]) with immune evasion mRNAs (E3, K3, and B18R [EKB]) from vaccinia virus. Additionally, we included mature, double-stranded microRNAs (miRNAs) from the 302/367 cluster, which are known to enhance the reprogramming process, to develop a robust reprogramming protocol for the generation of stable iPS cell lines from both human fibroblasts and human blood-outgrowth endothelial progenitor cells (EPCs). Our novel combination of RNAs enables the cell to tolerate repetitive transfections for the generation of stable iPS cell colonies from human fibroblasts within 11 days while requiring only four transfections. Moreover, our method resulted in the first known mRNA-vectored reprogramming of human blood-derived EPCs within 10 days while requiring only eight daily transfections. PMID- 26381597 TI - Effectiveness of work skills programmes for offenders with mental disorders: A systematic review. AB - BACKGROUND: Academic literature and government initiatives have emphasised the importance of work as a means of improving health and reducing reoffending among offenders with mental disorders. Whilst a number of work skills programmes have shown promise for offenders more generally, evaluation of evidence for their effectiveness for those with a mental disorder is lacking, particularly in relation to improving employment outcomes. AIMS: To assess the evidence on the effectiveness of work skills programmes for mentally disordered offenders. METHOD: A systematic review of the literature was conducted by searching the following databases: PsycINFO, CINAHL, Cochrane Library (Trials Register), Embase and Medline, using search terms which included Work Skills Programme*, Offend* and Mental*. Any empirical comparison study of work skills programmes was included in this review. The primary outcome was employment. Secondary outcomes included employment outcomes, reoffending, education, mental state, substance misuse, global functioning, quality of life, acceptability, leaving the study early and cost effectiveness or other economic outcomes. RESULTS: Six articles met the inclusion criteria. Collectively they provided limited evidence that work skills programmes increase the likelihood of people with mental disorder who are offenders obtaining employment in the short term, but there are insufficient studies to determine the long-term impact of work skills programmes. CONCLUSIONS: There is modest evidence to support inclusion of specific work skills programmes in the treatment of offenders with mental disorder. Future studies should be of theoretically driven programmes, such as Individual Placement Support (IPS), and use a standard set of relevant outcome measures and long enough follow-up for testing the effectiveness of any programme on engagement in competitive, paid employment as, even if skilled, offenders with mental disorder must constitute a hard to place group. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26381598 TI - Application of modified antisense oligonucleotides and siRNAs as antiviral drugs. PMID- 26381599 TI - Moderate water stress prevents the postharvest decline of ascorbic acid in spinach (Spinacia oleracea L.) but not in spinach beet (Beta vulgaris L.). AB - BACKGROUND: Babyleaf salads such as spinach (Spinacia oleracea L.) and spinach beet (Beta vulgaris L. subsp. cicla var. cicla) are an important dietary source of antioxidants such as ascorbic acid (vitamin C). Such compounds may be important in disease prevention in consumers but the level of these compounds in leaves frequently declines after harvest. As such, methods to maintain antioxidant levels in fresh produce are being sought. RESULTS: Irrigation deficits were used to apply water stress to S. oleracea and B. vulgaris plants. This treatment prevented postharvest decline of leaf ascorbic acid content in S. oleracea but not in B. vulgaris. Ascorbic acid levels in leaves at harvest were unaffected by the treatment in both species compared to well-watered controls. CONCLUSION: We have shown that restricted irrigation provides a viable means to maintain leaf vitamin content after harvest in S. oleracea, an important finding for producers, retailers and consumers alike. (c) 2015 Society of Chemical Industry. PMID- 26381600 TI - Nebulized Tranexamic Acid as a Noninvasive Therapy for Cancer-Related Hemoptysis. AB - BACKGROUND: Many patients with cancer involving the respiratory system suffer from the frequent recurrence of significant, submassive hemoptysis, which may result in invasive procedures, hospital stays, and a reduction in quality of life. Currently, there are no widely accepted noninvasive therapeutic options. Few case studies have looked at the benefit of tranexamic acid (TXA) as a noninvasive therapy in the treatment of hemoptysis. METHODS: A patient with an invasive airway malignancy presented to the emergency department with substantial hemoptysis. A nebulized TXA solution was used as a noninvasive therapy to control the hemorrhage. RESULTS: The patient's hemoptysis resolved fifteen minutes after the nebulized TXA therapy was initiated. There were no known adverse events. CONCLUSION: Nebulized TXA seems to be a safe, effective, and noninvasive method for controlling, or at least temporizing, hemoptysis in select patients. Nebulized TXA may be useful as a palliative therapy for chronic hemoptysis and as a tool in the acute stabilization of hemoptysis. PMID- 26381601 TI - TAK1 inhibition-induced RIP1-dependent apoptosis in murine macrophages relies on constitutive TNF-alpha signaling and ROS production. AB - BACKGROUND: Transforming growth factor-beta (TGF-beta)-activated kinase 1 (TAK1) is a key regulator of signal cascades of TNF-alpha receptor and TLR4, and can induce NF-kappaB activation for preventing cell apoptosis and eliciting inflammation response. RESULTS: TAK1 inhibitor (TAKI) can decrease the cell viability of murine bone marrow-derived macrophages (BMDM), RAW264.7 and BV-2 cells, but not dermal microvascular endothelial cells, normal human epidermal keratinocytes, THP-1 monocytes, human retinal pigment epithelial cells, microglia CHME3 cells, and some cancer cell lines (CL1.0, HeLa and HCT116). In BMDM, TAKI induced caspase activation and cell apoptosis were enhanced by lipopolysaccharide (LPS). Moreover, TAKI treatment increased the cytosolic and mitochondrial reactive oxygen species (ROS) production, and ROS scavengers NAC and BHA can inhibit cell death caused by TAKI. In addition, RIP1 inhibitor (necrostatin-1) can protect cells against TAKI-induced mitochondrial ROS production and cell apoptosis. We also observed the mitochondrial membrane potential loss after TAKI treatment and deterioration of oxygen consumption upon combination with LPS. Notably TNF-alpha neutralization antibody and inhibitor enbrel can decrease the cell death caused by TAKI. CONCLUSIONS: TAKI-induced cytotoxicity is cell context specific, and apoptosis observed in macrophages is dependent on the constitutive autocrine action of TNF-alpha for RIP1 activation and ROS production. PMID- 26381602 TI - Metal nanoparticle assisted polymerase chain reaction for strain typing of Salmonella Typhi. AB - Salmonella enterica serotype Typhi (S. Typhi) is the causative agent of typhoid fever and remains a major health threat in most of the developing countries. The prompt diagnosis of typhoid directly from the patient's blood requires high level of sensitivity and specificity. Some of us were the first to report PCR based diagnosis of typhoid. This approach has since then been reported by many scientists using different genomic targets. Since the number of bacteria circulating in the blood of a patient can be as low as 0.3 cfu ml(-1), there is always a room for improvement in diagnostic PCR. In the present study, the role of different types of nanoparticles was investigated to improve the existing PCR based methods for diagnosis and strain typing of S. Typhi (targeting Variable Number of Tandem Repeats [VNTR]) by using optimized PCR systems. Three different types of nanoparticles were used i.e., citrate stabilized gold nanoparticles, rhamnolipid stabilized gold and silver nanoparticles, and magnetic iron oxide nanoparticles. The non-specific amplification was significantly reduced in VNTR typing when gold and silver nanoparticles were used in an appropriate concentration. More importantly, the addition of nanoparticles decreased the non specificity to a significant level in the case of multiplex PCR thus further validating the reliability of PCR for the diagnosis of typhoid. PMID- 26381603 TI - Secular trends in consultations for asthma in early childhood, the 16 administrative regions of Morocco, 2004-2012. AB - BACKGROUND: Little is known about asthma trend in Morocco, particularly in early childhood. Furthermore, when dealing with asthma related environmental risk factors in Morocco, decision-making focus is in one region R9, while 16 regions make up the country. This work aims at studying 9-year trends in consultations for asthma in under-5 children in the 16 individual regions with respect to area and age group. METHODS: Direct method use, based on the only available national data from the open access files of the ministry of health, standardizing data for three age groups (0-11 ; 12-23 and 24-59 months). We compared age-adjusted rates, stratified by area (urban and rural areas) within each region (Wilcoxon's signed ranks test), and between all regions emphasizing on R9. Secular trends are examined (Kendall's rank correlation test). We also compared directly standardized rates as a rate ratio for two study populations (that of R9 and any region with highest rates). We finally compared rates by age group in selected regions. RESULTS: Secular increase in prevalence rates was shown in both urban and rural Morocco, particularly in urban areas of R10, R14, R16 and R5, and in rural areas of R14 and R16. In urban area of R10 (the highest age-adjusted prevalence rates area) the rates showed secular increase from 6.82 at 95 % CI = [6.44 to 7.19] per 1000 childhood population in 2004 to 20.91 at 95 % CI = [20.26 to 21.56] per 1000 childhood population in 2012 (P = 0.001). Rates were higher in urban than rural Morocco, particularly in R8, R9, R10, R14, R15 ; R6 was an exception. Rates in R10 were 1.63 higher than that in R9 in 2004 and rose to be 2.55 higher in 2012 ; rates in urban area of R14, about 3 times lower than that in R9 in 2004, increased to be similar in 2012. The highest-prevalence age group varied according to region and area. DISCUSSION: The regions that worth decision making attention are the urban areas of R10 (the highest prevalence rates Moroccan area, showing continuous increase), of R9, of R14 and the rural area of R6. The rates in the urban area of R9 (a current continuous decision making focus) remained high but stable within the study period and less important than those in R10. Environmental factors (biological particules, non-biological particules or gazes) are suspected.The potential unavailability of treatment at regular basis at the primary health care centers may reduce frequency of consultations for asthma in early childhood : outpatients may consult only if asthma causes problems in an attempt to get free medicines ; chances of outpatients' follow-up by the primary health care center's physicians are therefore reduced and optimal asthma control is not achieved. CONCLUSION: Social, health care policy and environmental factors, to which decision-making has to be responsive, are suspected to be affecting both frequency of and time secular trend in consultations for asthma in early childhood in Morocco. PMID- 26381604 TI - Meier-Gorlin syndrome. AB - Meier-Gorlin syndrome (MGS) is a rare autosomal recessive primordial dwarfism disorder, characterized by microtia, patellar applasia/hypoplasia, and a proportionate short stature. Associated clinical features encompass feeding problems, congenital pulmonary emphysema, mammary hypoplasia in females and urogenital anomalies, such as cryptorchidism and hypoplastic labia minora and majora. Typical facial characteristics during childhood comprise a small mouth with full lips and micro-retrognathia. During ageing, a narrow, convex nose becomes more prominent. The diagnosis MGS should be considered in patients with at least two of the three features of the clinical triad of microtia, patellar anomalies, and pre- and postnatal growth retardation. In patients with short stature and/or microtia, the patellae should be assessed with care by ultrasonography before age 6 or radiography thereafter. Mutations in one of five genes (ORC1, ORC4, ORC6, CDT1, and CDC6) of the pre-replication complex, involved in DNA-replication, are detected in approximately 67-78% of patients with MGS. Patients with ORC1 and ORC4 mutations appear to have the most severe short stature and microcephaly. Management should be directed towards in-depth investigation, treatment and prevention of associated problems, such as growth retardation, feeding problems, hearing loss, luxating patellae, knee pain, gonarthrosis, and possible pulmonary complications due to congenital pulmonary emphysema with or without broncho- or laryngomalacia. Growth hormone treatment is ineffective in most patients with MGS, but may be effective in patients in whom growth continues to decrease after the first year of life (usually growth velocity normalizes after the first year) and with low levels of IGF1. At present, few data is available about reproduction of females with MGS, but the risk of premature labor might be increased. Here, we propose experience-based guidelines for the regular care and treatment of MGS patients. PMID- 26381605 TI - TMFoldWeb: a web server for predicting transmembrane protein fold class. AB - BACKGROUND: Here we present TMFoldWeb, the web server implementation of TMFoldRec, a transmembrane protein fold recognition algorithm. TMFoldRec uses statistical potentials and utilizes topology filtering and a gapless threading algorithm. It ranks template structures and selects the most likely candidates and estimates the reliability of the obtained lowest energy model. The statistical potential was developed in a maximum likelihood framework on a representative set of the PDBTM database. According to the benchmark test the performance of TMFoldRec is about 77 % in correctly predicting fold class for a given transmembrane protein sequence. RESULTS: An intuitive web interface has been developed for the recently published TMFoldRec algorithm. The query sequence goes through a pipeline of topology prediction and a systematic sequence to structure alignment (threading). Resulting templates are ordered by energy and reliability values and are colored according to their significance level. Besides the graphical interface, a programmatic access is available as well, via a direct interface for developers or for submitting genome-wide data sets. CONCLUSIONS: The TMFoldWeb web server is unique and currently the only web server that is able to predict the fold class of transmembrane proteins while assigning reliability scores for the prediction. This method is prepared for genome-wide analysis with its easy-to-use interface, informative result page and programmatic access. Considering the info-communication evolution in the last few years, the developed web server, as well as the molecule viewer, is responsive and fully compatible with the prevalent tablets and mobile devices. PMID- 26381607 TI - Paraspinal morphea (paraspinal fibrosing plaque): differentiation from other paraspinal entities. PMID- 26381606 TI - Measuring patient experiences on hospitalist and teaching services: Patient responses to a 30-day postdischarge questionnaire. AB - BACKGROUND: Data comparing patient experiences between general medicine teaching and nonteaching hospitalist services are lacking. OBJECTIVE: Evaluate hospitalized patients' experience on general medicine teaching and nonteaching hospitalist services by assessing patients' confidence in their ability to identify their physician(s), understand their roles, and their rating of the coordination and overall care. METHODS: Retrospective cohort analysis of general medicine teaching and nonteaching hospitalist services from 2007 to 2013 at an academic medical center. Patients were surveyed 30-days after hospital discharge regarding their confidence in their ability to identify their physician(s), understand the role of their physician(s), and their perceptions of coordination and overall care. A 3-level, mixed effects logistic regression was performed to ascertain the association between service type and patient-reported outcomes. RESULTS: Data from 4591 general medicine teaching and 1811 nonteaching hospitalist service patients demonstrated that those cared for by the hospitalist service were more likely to report being able to identify their physician (50% vs 45%, P < 0.001), understand their role (54% vs 50%, P < 0.001), and rate greater satisfaction with coordination (68 vs 64%, P = 0.006) and overall care (73% vs 67%, P < 0.001). In regression models, the hospitalist service was associated with higher ratings in overall care (odds ratio [OR]: 1.33; 95% confidence interval [CI]: 1.15-1.47), even when hospitalists were the attendings on general medicine teaching services (OR: 1.17; 95% CI: 1.01-1.31). CONCLUSION: Patients on a nonteaching hospitalist service rated their overall care slightly better than patients on a general medicine teaching service. Team structure and complexity may play a role in this difference. PMID- 26381608 TI - An experimental field evaluation of winter carryover effects in semi-anadromous brown trout (Salmo trutta). AB - For semi-anadromous brown trout, the decision whether or not to smoltify and migrate to the sea is believed to be made at the end of the preceding summer in response to both local environmental conditions and individual physiological status. Stressors experienced during the fall may therefore influence their propensity to migrate as well as carry over into the winter resulting in mortality when fish face challenging environmental conditions. To evaluate this possibility, we artificially elevated cortisol levels in juvenile trout (via intracoelomic injection of cortisol in the fall) and used passive integrated transponder tags to compare their overwinter and spring survival, growth, and migration success relative to a control group. Results suggest that overwinter mortality is high for individuals in this population regardless of treatment. However, survival rates were 2.5 times lower for cortisol-treated fish and they experienced significantly greater loss in mass. In addition, less than half as many cortisol-treated individuals made it downstream to a stationary antenna over the winter and also during the spring migration compared to the control treatment. These results suggest that a fall stressor can reduce overwinter survival of juvenile brown trout, negatively impact growth of individuals that survive, and ultimately result in a reduction in the number of migratory trout. Carryover effects such as those documented here reveal the cryptic manner in which natural and anthropogenic stressors can influence fish populations. J. Exp. Zool. 323A: 645-654, 2015. (c) 2015 Wiley Periodicals, Inc. PMID- 26381609 TI - Characteristics of the home food environment that mediate immediate and sustained increases in child fruit and vegetable consumption: mediation analysis from the Healthy Habits cluster randomised controlled trial. AB - BACKGROUND: The home food environment can influence the development of dietary behaviours in children, and interventions that modify characteristics of the home food environment have been shown to increase children's fruit and vegetable consumption. However to date, interventions to increase children's fruit and vegetable consumption have generally produced only modest effects. Mediation analysis can help in the design of more efficient and effective interventions by identifying the mechanisms through which interventions have an effect. This study aimed to identify characteristics of the home food environment that mediated immediate and sustained increases in children's fruit and vegetable consumption following the 4-week Healthy Habits telephone-based parent intervention. METHOD: Analysis was conducted using 2-month (immediate) and 12-month (sustained) follow up data from a cluster randomised control trial of a home food environment intervention to increase the fruit and vegetable consumption of preschool children. Using recursive path analysis, a series of mediation models were created to investigate the direct and indirect effects of immediate and sustained changes to characteristics of the home food environment (fruit and vegetable availability, accessibility, parent intake, parent providing behaviour, role modelling, mealtime eating practices, child feeding strategies, and pressure to eat), on the change in children's fruit and vegetable consumption. RESULTS: Of the 394 participants in the randomised trial, 357 and 329 completed the 2- and 12 month follow-up respectively. The final mediation model suggests that the effect of the intervention on the children's fruit and vegetable consumption was mediated by parent fruit and vegetable intake and parent provision of these foods at both 2- and 12-month follow-up. CONCLUSION: Analysis of data from the Healthy Habits trial suggests that two environmental variables (parental intake and parent providing) mediate the immediate and sustained effect of the intervention, and it is recommended these variables be targeted in subsequent home food environment interventions to bring about immediate and sustained changes in child fruit and vegetable intake. TRIAL REGISTRATION: ACTRN12609000820202 . PMID- 26381610 TI - Symphyseal surface strain during in vitro human mandibular wishboning. AB - OBJECTIVES: This research theoretically models and empirically records symphyseal surface strain during in vitro human mandibular wishboning (lateral transverse bending) in order to test one aspect of the hypothesis that the chin is an adaptive response to masticatory stresses. From a perspective of optimality, three questions were tested: 1) Do human mandibles function as curved beams during wishboning? 2) Is the presence of a chin associated with lower than predicted curved beam effects? 3) Are there relatively low strain gradients on the lingual and labial symphyseal surfaces respectively? MATERIALS AND METHODS: Based on morphometric criteria, theoretical wishboning strains were calculated for five dentate adult human mandibles. The same mandibles were fitted with strain gauges and subjected to simulated wishboning loads. From the empirically recorded strains, relative strains were calculated by dividing all strains by the absolute lowest strain in a given specimen. The theoretical and empirical results were compared in order to address the three related questions guiding this research. RESULTS: Human mandibles behave as curved beams during wishboning (question 1). Empirical strain measures showed greater disparity both between and within the labial and lingual symphyseal surfaces than the theoretical models predictions (questions 2 and 3). DISCUSSION: Human symphyseal form, with its distinctive chin, is unlikely to be adapted for countering wishboning loads. Chins are associated with larger than expected strain gradients within and between symphyseal surfaces, which runs counter to the optimality criterion typically invoked in assessing trait performance for signs of adaptation. The implications are twofold: 1) wishboning may not, in fact, be a regular feature of human mastication or 2) wishboning may not pose the same structural risks in human jaws as this load does in other anthropoid primates. PMID- 26381612 TI - Thermoluminescence and photoluminescence studies on gamma-ray-irradiated Ce3+,Tb3+-doped potassium chloride single crystals. AB - Single crystals of KCl doped with Ce(3+),Tb(3+) were grown using the Bridgeman Stockbarger technique. Thermoluminescence (TL), optical absorption, photoluminescence (PL), photo-stimulated luminescence (PSL), and thermal stimulated luminescence (TSL) properties were studied after gamma-ray irradiation at room temperature. The glow curve of the gamma-ray-irradiated crystal exhibits three peaks at 420, 470 and 525 K. F-Light bleaching (560 nm) leads to a drastic change in the TL glow curve. The optical absorption measurements indicate that F- and V-centres are formed in the crystal during gamma-ray irradiation. It was attempted to incorporate a broad band of cerium activator into the narrow band of terbium in the KCl host without a reduction in the emission intensity. Cerium co doped KCl:Tb crystals showed broad band emission due to the d-f transition of cerium and a reduction in the intensity of the emission peak due to (5)D3 (7)F(j) (j = 3, 4) transition of terbium, when excited at 330 nm. These results support that energy transfer occurs from cerium to terbium in the KCl host. Co doping Ce(3+) ions greatly intensified the excitation peak at 339 nm for the emission at 400 nm of Tb(3+). The emission due to Tb(3+) ions was confirmed by PSL and TSL spectra. PMID- 26381613 TI - Chemical Gated Field Effect Transistor by Hybrid Integration of One-Dimensional Silicon Nanowire and Two-Dimensional Tin Oxide Thin Film for Low Power Gas Sensor. AB - Gas sensors based on metal-oxide-semiconductor transistor with the polysilicon gate replaced by a gas sensitive thin film have been around for over 50 years. These are not suitable for the emerging mobile and wearable sensor platforms due to operating voltages and powers far exceeding the supply capability of batteries. Here we present a novel approach to decouple the chemically sensitive region from the conducting channel for reducing the drive voltage and increasing reliability. This chemically gated field effect transistor uses silicon nanowire for the current conduction channel with a tin oxide film on top of the nanowire serving as the gas sensitive medium. The potential change induced by the molecular adsorption and desorption allows the electrically floating tin oxide film to gate the silicon channel. As the device is designed to be normally off, the power is consumed only during the gas sensing event. This feature is attractive for the battery operated sensor and wearable electronics. In addition, the decoupling of the chemical reaction and the current conduction regions allows the gas sensitive material to be free from electrical stress, thus increasing reliability. The device shows excellent gas sensitivity to the tested analytes relative to conventional metal oxide transistors and resistive sensors. PMID- 26381611 TI - Emergence and evolution of internationally disseminated cephalosporin-resistant Neisseria gonorrhoeae clones from 1995 to 2005 in Japan. AB - BACKGROUND: Neisseria gonorrhoeae strains with resistance to extended-spectrum cephalosporins (ESCs), last options for first-line monotherapy of gonorrhoea, likely emerged and initially disseminated in Japan, followed by international transmission. In recent years, multi-locus sequence typing (MLST) ST1901 and N. gonorrhoeae multiantigen sequence typing (NG-MAST) ST1407 isolates with the mosaic penicillin-binding protein (PBP) 2 XXXIV have accounted for most ESC resistance globally. Our aim was to elucidate the initial emergence and transmission of ESC-resistant strains by detailed examination of N. gonorrhoeae isolates from 1995 to 2005 in Kanagawa, Japan. METHODS: N. gonorrhoeae isolates were examined phenotypically (n = 690) and genetically (n = 372) by agar dilution method (cefixime, ceftriaxone and ciprofloxacin), penA gene sequencing, MLST and NG-MAST. RESULTS: Already in 1995, one cefixime-resistant (CFM-R) isolate was found, which is the first CFM-R isolate described globally. After 1996, the prevalence of CFM-R and CFM-decreased susceptibility (CFM-DS) isolates significantly increased, with the peak resistance level in 2002 (57.1% CFM-R). In 1997-2002, the CFM-R MLST ST7363 strain type with the mosaic PBP 2 X was predominant among CFM-R/DS isolates. The first CFM-R/DS MLST ST1901 clone(s), which became the predominant CFM-R/DS strain type(s) already in 2003-2005, possessed the mosaic PBP 2 X, which was possibly originally transferred from the MLST ST7363 strains, and subsequently acquired the mosaic PBP 2 XXXIV. The first MLST ST1901 and NG-MAST ST1407 isolate was identified in Kanagawa already in 2003. CONCLUSIONS: The two main internationally spread cefixime-resistant gonococcal clones, MLST ST7363 and ST1901 (NG-MAST ST1407 most frequent internationally) that also have shown their capacity to develop high-level ceftriaxone resistance (superbugs H041 and F89), likely emerged, evolved and started to disseminate in the metropolitan area, including Kanagawa, in Japan, which was followed by global transmission. PMID- 26381615 TI - Editorial: Painting by numbers: using modern approaches to analyse and visualise clinical and research data. PMID- 26381614 TI - Mitochondrial genomes of two phlebotomine sand flies, Phlebotomus chinensis and Phlebotomus papatasi (Diptera: Nematocera), the first representatives from the family Psychodidae. AB - BACKGROUND: Leishmaniasis is a worldwide but neglected disease of humans and animal transmitted by sand flies, vectors that also transmit other important diseases. Mitochondrial genomes contain abundant information for population genetic and phylogenetic studies, important in disease management. However, the available mitochondrial sequences of these crucial vectors are limited, emphasizing the need for developing more mitochondrial genetic markers. METHODS: The complete mitochondrial genome of Phlebotomus chinensis was amplified in eight fragments and sequenced using primer walking. The mitochondrial genome of Phlebotomus papatasi was reconstructed from whole-genome sequencing data available on Genbank. The phylogenetic relationship of 24 selected representatives of Diptera was deduced from codon positions 1 and 2 for 13 protein coding genes, using Bayesian inference (BI) and maximum likelihood (ML) methods. RESULTS: We provide the first Phlebotomus (P. chinensis and P. papatasi) mitochondrial genomes. Both genomes contain 13 protein-coding genes, 22 transfer RNA genes, two ribosomal RNA genes, and an A + T-rich region. The gene order of Phlebotomus mitochondrial genomes is identical with the ancestral gene order of insect. Phylogenetic analyses demonstrated that Psychodidae and Tanyderidae are sister taxa. Potential markers for population genetic study of Phlebotomus species were also revealed. CONCLUSION: The generated mitochondrial genomes of P. chinensis and P. papatasi represent a useful resource for comparative genomic studies and provide valuable future markers for the population genetic study of these important Leishmania vectors. Our results also preliminary demonstrate the phylogenetic placement of Psychodidae based on their mitochondrial genomes. PMID- 26381616 TI - Editor conflicts of interest statements, 2015. PMID- 26381617 TI - Erratum. PMID- 26381618 TI - Fluoride Modulates Parathyroid Hormone Secretion in vivo and in vitro. AB - The study objective was to investigate the effects of fluoride on intact parathyroid hormone (iPTH) secretion. Thyro-parathyroid complexes (TPC) from C3H (n = 18) and B6 (n = 18) mice were cultured in Ca2+-optimized medium. TPC were treated with 0, 250, or 500 uM NaF for 24 h and secreted iPTH assayed by ELISA. C3H (n = 78) and B6 (n = 78) mice were gavaged once with distilled or fluoride (0.001 mg [F-]/g of body weight) water. At serial time points (0.5-96 h) serum iPTH, fluoride, total calcium, phosphorus, and magnesium levels were determined. Expression of genes involved in mineral regulation via the bone-parathyroid kidney (BPK) axis, such as parathyroid hormone (Pth), calcium-sensing receptor (Casr), vitamin D receptor (Vdr), parathyroid hormone-like hormone (Pthlh), fibroblast growth factor 23 (Fgf23), alpha-Klotho (alphaKlotho), fibroblast growth factor receptor 1c (Fgf1rc), tumor necrosis factor 11 (Tnfs11), parathyroid hormone receptor 1 (Pth1r), solute carrier family 34 member 1 (Slc34a1), solute carrier 9 member 3 regulator 1 (Slc9a3r1), chloride channel 5 (Clcn5), and PDZ domain-containing 1 (Pdzk1), was determined in TPC, humeri, and kidneys at 24 h. An in vitro decrease in iPTH was seen in C3H and B6 TPC at 500 uM (p < 0.001). In vivo levels of serum fluoride peaked at 0.5 h in both C3H (p = 0.002) and B6 (p = 0.01). In C3H, iPTH decreased at 24 h (p < 0.0001), returning to baseline at 48 h. In B6, iPTH increased at 12 h (p < 0.001), returning to baseline at 24 h. Serum total calcium, phosphorus, and magnesium levels did not change significantly. Pth, Casr,alphaKlotho,Fgf1rc,Vdr, and Pthlh were significantly upregulated in C3H TPC compared to B6. In conclusion, the effects of fluoride on TPC in vitro were equivalent between the 2 mouse strains. However, fluoride demonstrated an early strain-dependent effect on iPTH secretion in vivo. Both strains demonstrated differences in the expression of genes involved in the BPK axis, suggesting a possible role in the physiologic handling of fluoride. PMID- 26381619 TI - Treatment of Small Vessel Disease With the Paclitaxel Drug-Eluting Balloon: 6 Month Angiographic and 1-Year Clinical Outcomes of the Spanish Multicenter Registry. AB - BACKGROUND: Small vessel disease (SMD) remains a major challenge because of the increased risk of restenosis. We sought to assess the efficacy and safety of a paclitaxel-eluting balloon (PEB) in patients with SMD. METHODS AND RESULTS: One hundred and four patients with native coronary lesions in small vessels treated by using a PEB were included in this prospective multicenter registry. In each case, after regular balloon dilatation, a larger PEB was inflated for a minimum of 45-60 seconds. Patients were 65 +/- 10 years old, 43% diabetic, and 58% presented acutely. Angiographic success was 93% (7% bailout BMS implantation due to coronary dissection). The rate of major adverse cardiac events (MACE) at 12 months was 4.8% (1.9% cardiac death, 1.0% MI, and 2.9% TLR). One definite stent thrombosis was reported at 6 months in a patient with bailout BMS implantation. At 7 months, late loss was 0.31 +/- 0.2 mm. Bail-out BMS after DEB use, was an independent predictor of MACE, HR 18.74, 95%CI (2.58-135.84) and TLR, HR 30.99, 95%CI (2.79-344.07). CONCLUSION: The use of this PEB for the treatment of SMD provides excellent 1-year outcomes with only 4.8% MACE. The need for a bailout BMS was a strong predictor of MACE and TLR. PMID- 26381621 TI - ENETS News Letter. PMID- 26381620 TI - The effects of smoking and drinking on all-cause mortality in patients with dilated cardiomyopathy: a single-center cohort study. AB - SUBJECT: Recent studies have shown that smoking and drinking are associated with poorer outcomes in patients with cardiomyopathy. The purpose of this study was to determine all-cause mortality in dilated cardiomyopathy (DCM) associated with smoking and drinking. METHODS: An observational cohort study was undertaken in DCM patients from November 2003 to September 2011. A total of 1118 patients were enrolled, with a mean follow-up of 3.5 +/- 2.3 years. Standard demographics were obtained, and transthoracic echocardiography and routine blood testing were performed shortly after admission. Outcome assessment was based on the all-cause death after admission. RESULTS: The patients were divided into three groups: non smokers (n = 593), mild-to-moderate smokers (n = 159) and heavy smokers (n = 366). The all-cause mortality rates showed no differences between the three groups (23.8, 20.8 and 24 %, respectively; log-rank chi (2) = 1.281, P = 0.527). There was also no significant difference in mortality between non-drinkers (n = 747), mild drinkers (n = 142) and moderate drinkers (n = 229) (23.7, 23.2 and 22.3 %, respectively; log-rank chi (2) = 2.343, P = 0.310). In the Cox analysis, neither the smoking (HR 0.971, P = 0.663) nor the drinking status (HR 0.891, P = 0.140) was a significant independent predictor of all-cause mortality in patients with DCM. CONCLUSION: In conclusion, there were no significant differences in mortality between the smoking- and drinking-related patient groups, indicating no effect of smoking and drinking on all-cause mortality in patients with DCM in the present large-scale study. PMID- 26381622 TI - Learning without Borders: A Review of the Implementation of Medical Error Reporting in Medecins Sans Frontieres. AB - OBJECTIVE: To analyse the results from the first 3 years of implementation of a medical error reporting system in Medecins Sans Frontieres-Operational Centre Amsterdam (MSF) programs. METHODOLOGY: A medical error reporting policy was developed with input from frontline workers and introduced to the organisation in June 2010. The definition of medical error used was "the failure of a planned action to be completed as intended or the use of a wrong plan to achieve an aim." All confirmed error reports were entered into a database without the use of personal identifiers. RESULTS: 179 errors were reported from 38 projects in 18 countries over the period of June 2010 to May 2013. The rate of reporting was 31, 42, and 106 incidents/year for reporting year 1, 2 and 3 respectively. The majority of errors were categorized as dispensing errors (62 cases or 34.6%), errors or delays in diagnosis (24 cases or 13.4%) and inappropriate treatment (19 cases or 10.6%). The impact of the error was categorized as no harm (58, 32.4%), harm (70, 39.1%), death (42, 23.5%) and unknown in 9 (5.0%) reports. Disclosure to the patient took place in 34 cases (19.0%), did not take place in 46 (25.7%), was not applicable for 5 (2.8%) cases and not reported for 94 (52.5%). Remedial actions introduced at headquarters level included guideline revisions and changes to medical supply procedures. At field level improvements included increased training and supervision, adjustments in staffing levels, and adaptations to the organization of the pharmacy. CONCLUSION: It was feasible to implement a voluntary reporting system for medical errors despite the complex contexts in which MSF intervenes. The reporting policy led to system changes that improved patient safety and accountability to patients. Challenges remain in achieving widespread acceptance of the policy as evidenced by the low reporting and disclosure rates. PMID- 26381624 TI - Dental insurance: Boulevard for stakeholders. PMID- 26381623 TI - Spatio-Temporal Variations in Malaria Incidence in Children Less than 10 Years Old, Health District of Sokone, Senegal, 2010-2013. AB - INTRODUCTION: Malaria is a leading cause of morbidity and mortality in sub Saharan Africa. Detailed characterization of the risks for malaria, among populations living in areas where the disease is endemic, is an important priority, especially for planning and evaluating future malaria-control tools. A prospective cohort study was implemented in children under ten years living in rural areas with high Plasmodium falciparum transmission in Senegal. METHODS: Malaria incidence was prospectively evaluated over three year follow-up among a cohort of children aged less than 10 years old living in eight villages of the Sokone health district. The parents of 1316 children comprising a passive case detection cohort were encouraged to seek care from the study health centers at any time their child felt sick. In the event of reported history of fever within 24 hours or measured axillary temperature >= 37.5 degrees C, a Rapid Diagnostic Test (RDT) was performed. RESULTS: From November 2010 to October 2013, among the 1468 reported febrile episodes, 264 were confirmed malaria episodes. Over the 3 years, 218 (16.9%) children experienced at least one clinical malaria episode. Cumulative malaria incidence was 7.3 episodes per 100 children-year at risk, with remarkably heterogeneous rates from 2.5 to 10.5 episodes per 100 children-year at risk. Clinical malaria prevalence ranged from 11.5 to 28.4% in the high transmission season versus from 9.6 to 21.2% in the low transmission season. CONCLUSION: This longitudinal community-based study shows that occurrence of clinical malaria was not evenly distributed among all the cohort children in the eight villages. It demonstrates the complexity of spatial distribution of malaria incidence at a local level, even in a region of vegetation and altitudinal homogeneity. PMID- 26381625 TI - Phentolamine mesylate: It's role as a reversal agent for unwarranted prolonged local analgesia. AB - Administration of local anesthesia is an integral procedure prior to dental treatments to minimize the associated pain. It is learned that its effect stays more than the time required for the dental procedure to be completed. This prolonged soft tissue anesthesia (STA) can be detrimental, inconvenient, and unnecessary. Phentolamine mesylate, a Food and Drug Administration-approved drug essentially serves the purpose of faster recovery from numbness at the site of local anesthesia. This article reviews the development of the drug phentolamine mesylate and its indication as a local anesthetic reversal agent. A literature search for phentolamine mesylate as a STA reversal agent was conducted in PubMed using the terms "dental local anesthesia reversal, phentolamine mesylate" up to March 2014. The search was limited to articles published in English. The search revealed 13 PubMed indexed articles stating the development and application of phentolamine mesylate. Phentolamine mesylate is an important step in the progress of developing patient care as well as an aid to the dental clinician. PMID- 26381626 TI - Effect of casein phosphopeptide-amorphous calcium phosphate (cpp-acp) on caries like lesions in terms of time and nano-hardness: An in vitro study. AB - CONTEXT: Time bound increase in the nanohardness of the enamel after remineralization with casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) in a regular interval of 1 h has not been explored in the literature to a greater extent. AIMS: To determine and compare the maximum hardness of the remineralized caries-like lesions, in terms of nanohardness and the rate of achieving maximum hardness at 1-h interval, after treatment with artificial saliva and CPP-ACP, over 12 h. MATERIALS AND METHODS: Fifty longitudinal sections of extracted sound permanent maxillary central, lateral incisors were immersed in demineralizing solution for 4 days. The samples were then randomly divided into three groups, consisting of 12 sections each for soaking them in three different media-isotonic saline, artificial saliva, and CPP-ACP for 12 h. The nanohardness was measured on the labial surface, at baseline, after erosion, and after remineralization at 1-h interval. STATISTICAL ANALYSIS USED: The data was analyzed with paired t-test, one-way analysis of variance (ANOVA) and post-hoc analysis. RESULTS: CPP-ACP increased the enamel hardness significantly (P < 0.001), at an increased rate, than artificial saliva. CONCLUSIONS: This study has provided an insight into the frequency of use of CPP-ACP, once per day, as the nanohardness of enamel samples increased within 1 h of application and remained within the normal limits after 12 h. PMID- 26381627 TI - Comparative evaluation of antimicrobial activity of hydroalcoholic extract of Aloe vera, garlic, and 5% sodium hypochlorite as root canal irrigants against Enterococcus faecalis: An in vitro study. AB - INTRODUCTION: Enterococcus faecalis are the most resistant and predominant microorganisms recovered from root canals of teeth where previous treatment has failed. Over the past decade, interest in drugs derived from medicinal plants has markedly increased. In dentistry, phytomedicines has been used as an anti inflammatory, antibiotic, analgesic, sedative, and also as an endodontic irrigant. In endodontics, because of the cytotoxic reactions of most of the commercial intracanal medicaments and their inability to eliminate bacteria completely from dentinal tubules, the trend is shifting toward use of biologic medication extracted from natural plants. AIM: To compare the antimicrobial efficacy of newer irrigating agents which would probably be as effective or more and at the same time less irritating to the tissues than sodium hypochlorite (NaOCl). The objective of this study was to compare the antimicrobial activity of saturated and diluted (1:1) hydroalcoholic extract of Aloe vera, garlic, and 5% NaOCl against E. faecalis using the commonly used agar diffusion method. RESULTS: Saturated hydroalcoholic extract of A. vera showed the highest zone of inhibition against E. faecalis. NaOCl, which is considered as gold standard, also showed higher zones of inhibition. PMID- 26381628 TI - Comparative evaluation of microleakage of conventional and modifications of glass ionomer cement in primary teeth: An in vitro study. AB - AIMS: The aim of the present study was to evaluate the microleakage among conventional, resin modified glass ionomer cements (GIC), and compomer cements in primary teeth. MATERIALS AND METHODS: Forty-five over retained non carious primary molars beyond exfoliation time were collected and randomly divided into three groups (n = 15). Group A: GC Fuji II; Group B: Vitremer; Group C: Compoglass F. A standard Class V cavity was prepared on the buccal surface of each tooth with no mechanical retention and restored accordingly. Then all the samples were subjected to thermocycling for 250 cycles at different temperatures and covered with nail varnish. Later, samples were immersed in 0.5% methylene blue dye for 24 h. Teeth were sectioned buccolingually through the center of the restoration and studied under a stereomicroscope for dye penetration. Data obtained were analyzed using Kruskal-Wallis ANOVA and Mann-Whitney U-test. RESULTS: Samples restored with vitremer showed comparatively higher microleakage than the samples in other groups. However, overall there were no significant difference between the microleakage scores of the samples in all three groups (P > 0.05). CONCLUSION: It can be concluded that none of the three GICs was free from microleakage. Hence, further research is required to compare microleakage of the newer material. PMID- 26381629 TI - Effectiveness of lidocaine Denti patch(r) system versus lidocaine gel as topical anesthetic agent in children. AB - BACKGROUND: New methods have been introduced to facilitate dental procedures, but the administration of local anesthesia is still necessary to perform pain control during several dental procedures. AIM: To evaluate the effectiveness of the lidocaine Denti-patch(r) system versus the lidocaine topical anesthetic gel in children concerning pain reaction during injection. MATERIALS AND METHODS: One hundred 9-12-year-old cooperative children weighing more than 29 kg in need of bilateral dental treatment requiring maxillary and mandibular injection and not suffering from acute pain as a result of pulpits on the day of treatment were selected. The children were then divided into two groups: Group 1 comprising of 50 children in need of bilateral maxillary treatment and Group 2 compromising of 50 children requiring bilateral mandibular treatment. These groups were further subdivided into subgroups A and B; those receiving Denti-patch(r) on one side and lidocaine gel on the contralateral side, respectively. Pain or comfort was evaluated during injection using sound, eye, motor (SEM) scale (objective method) while, using faces pain rating scale (FPS) scale (subjective method) after injection by a trained assistant blinded to the procedure. STATISTICAL ANALYSIS USED: Comparison of the results was performed using Mann-Whitney U-test and Wilcoxon signed-ranks test for SEM and FPS score. RESULT: There was a statistically significant difference between the patch and the gel group for maxilla (P < 0.0001), as well as mandible (P = 0.01) with respect to SEM score given by the children. Similarly, with FPS scale, there was a statistically significant difference between the patch and the gel groups in both maxilla and mandible (P < 0.0001). However, there was no statistical difference between the patch Groups 1A and IIA or the gel Groups 1B and II B. CONCLUSION: The Denti patch(r) system can significantly reduce the needle injection pain more than the gel. PMID- 26381630 TI - Comparative evaluation of the remineralizing efficacy of calcium sodium phosphosilicate agent and fluoride based on quantitative and qualitative analysis. AB - BACKGROUND: Calcium sodium phosphosilicate (NovaMin) is an agent that is claimed to release calcium and phosphate ions intraorally to help the self-repair process of enamel. It is used extensively as a desensitizing agent, but the chemical reactions that occur may promote apatite formation enhancing remineralization. The present study was undertaken to evaluate the ability of NovaMin to remineralize an experimentally induced demineralized lesion. The evaluation was done based on the quantitative and qualitative analysis of enamel over the period of 15 and 30 days. MATERIALS AND METHODS: A sample of 120 noncarious premolar teeth extracted for orthodontic reasons were used for the study. Baseline data for hardness, Ca/PO 4 , and surface characteristics before and after demineralization process was obtained. All the teeth were brushed twice daily at 12 h interval with the test agents using a powered toothbrush for 2 min. The samples were tested on the 15 th and 30 th day. RESULTS: Calcium phosphate ratio and hardness in both the groups improved during the study period. Fluoride group showed higher values for Ca/PO 4 and hardness but was not statistically significant with the P > 0.05. Scanning electron microscope pictures showed that the deposition of the material over the decalcified enamel is more smoother and uniform with NovaMin and more irregular with fluoride. RELEVANCE: NovaMin is found to be as effective in improving the Ca/PO 4 ratio and hardness in a demineralized enamel as fluoride. Hence, it can be a new alternate material for remineralization of enamel with less toxic effects compared to fluorides. PMID- 26381631 TI - Fracture resistance of endodontically treated permanent anterior teeth restored with three different esthetic post systems: An in vitro study. AB - BACKGROUND: Esthetic coronal reconstruction of fractured anterior teeth is often performed using intra radicular posts. Most of the commonly used commercially esthetic post systems do not exhibit similar physical properties as dentin resulting in failures. AIM: To evaluate and compare the fracture resistance and mode of failure of simulated traumatized permanent central incisors restored with three different post systems including biologic dentin posts. MATERIALS AND METHODS: A total of 40 recently extracted human maxillary central incisors with similar dimensions were decoronated 2 mm above the cemento-enamel junction and endodontically treated. Ten specimens were randomly selected as the Group I - Control group (core built teeth without intraradicular posts). The remaining 30 teeth were equally divided and restored with zirconia (Group II, n = 10), fiber re-inforced composite (FRC) (Group III, n = 10) and biologic dentin posts (Group IV, n = 10) using resin bonded cement and their cores built-up. These samples were embedded in acrylic resin and then secured in a Universal Testing Machine and subjected to fracture resistance testing. The location of failure in the specimens was evaluated using a stereomicroscope. RESULTS: Intergroup comparison revealed that the control group and zirconia post group (522 +/- 110 N) demonstrated the least fracture resistance, while dentin post group (721 +/- 127 N) the highest. There was no statistically significant difference between fiber post and dentin post groups. Fractures that were repairable were observed in fiber post and dentin post groups, whereas mostly unrestorable, catastrophic fractures were observed in the zirconia post group. CONCLUSION: Teeth restored with the biologic dentin post system demonstrated the highest fracture resistance and repairable fractures, closely followed by FRC post system. The least fracture resistance and most catastrophic fractures were demonstrated by the zirconia post system. PMID- 26381632 TI - Traumatic impact loading on human maxillary incisor: A Dynamic finite element analysis. AB - BACKGROUND: The most vulnerable tooth is the maxillary incisor, which sustains 80% of dental injuries. Dynamic Finite element analysis is used to understand the biomechanics of fracture of maxillary incisor under traumatic impact loading. AIM: The aim was to investigate the stress patterns of an upper incisor in a three-dimensional (3D) model under traumatic impact loading in various directions. MATERIALS AND METHODS: A 3D finite element model of the upper incisor and surrounding tissues was established. A sinusoidal force of 800N was applied over a period of 4 ms. RESULTS: Software performs a series of calculations and mathematical equations and yields the simulation results. During the horizontal impact (F1), stresses were concentrated in the cervical area of the crown, reaching peak stress of 125 MPa at 2 ms. CONCLUSION: A horizontal force exerted on the labial surface of the tooth tends to cause cervical crown fractures, oblique crown root fractures, and oblique root fractures. PMID- 26381633 TI - A cross-sectional study to assess the intelligence quotient (IQ) of school going children aged 10-12 years in villages of Mysore district, India with different fluoride levels. AB - INTRODUCTION: Besides dental and skeletal fluorosis, excessive fluoride intake can also affect the central nervous system without first causing the physical deformities associated with skeletal fluorosis. With the existence of widespread endemic fluorosis in India, the possible adverse effect of elevated fluoride in drinking water on the Intelligence Quotient (IQ) level of children is a potentially serious public health problem. AIMS AND OBJECTIVES: This study assessed the Intelligence Quotient (IQ) of school going children aged 10-12 years in villages of Mysore district with different fluoride levels. MATERIALS AND METHODS: In this cross-sectional study, 405 school children aged 10-12 years were selected from three villages in Mysore district with normal fluoride (1.20 mg F/l), low fluoride (0.40 mg F/l) and high fluoride (2.20 mg F/l) in their water supplies. A pre designed questionnaire was used to collect the required data for the survey which included socio demographic details, oral hygiene practices, diet history, body mass index and dental fluorosis. Intelligence Quotient was assessed using Raven's colored Progressive Matrices Test. RESULTS: In bivariate analysis, significant relationships were found between water fluoride levels and Intelligence Quotient of school children (P < 0.05). In the high fluoride village, the proportion of children with IQ below 90, i.e. below average IQ was larger compared to normal and low fluoride village. Age, gender, parent education level and family income had no significant association with IQ. CONCLUSION: School children residing in area with higher than normal water fluoride level demonstrated more impaired development of intelligence when compared to school children residing in areas with normal and low water fluoride levels. Thus, children's intelligence can be affected by high water fluoride levels. PMID- 26381634 TI - Prospective analysis of factors associated with dental behavior management problems, in children aged 7-11 years. AB - AIM: To determine the prevalence of child behavior management problems (BMP) and to analyze the influence and predictive power of nondental and dental background variables on BMP. STUDY DESIGN: Prospective analytical study. MATERIALS AND METHODS: The study group included 165 children aged 7-11 years who received comprehensive dental treatment, after obtaining written informed consent. Parents/guardians were interviewed using standardized questionnaire to obtain background information. Each child's treatment was carried out and was recorded with a fixed digital video (DV) recorder. The treatments were classified into three levels of invasiveness: Noninvasive (NI), moderately invasive (MI), and highly invasive (HI). The entire DV record of each treatment was observed, and child's dental behavior was rated independently by two precalibrated examiners using modified Venham's behavior rating scale. Then, the background factors obtained through the questionnaire data were analyzed for its association with child's dental behavior. RESULTS: Statistical tests used were Chi-square test and multiple logistic regression analysis to determine the relationship of multiple variables with dental behavior. Comparison of child's behavior during different visits was done by Wilcoxan matched pairs test. The prevalence of BMP in children aged 7-11 years in the study sample was 0%, 4.2%, and 15.76% for NI, MI, and HI procedures, respectively. Three variables were significant predictors of behavior; order of birth that is, first born, history of hospitalization, and unpleasant past dental experience (P < 0.05). CONCLUSIONS: Direct conditioning pathway is the major factor in determining child's behavior. Dental experiences, duration of treatment, and complexity of treatment have greater impact on how the child behaves in a dental setup. PMID- 26381635 TI - Evaluation of the accuracy of Demirjian method for estimation of dental age among 6-12 years of children in Navi Mumbai: A radiographic study. AB - BACKGROUND: Dental formation is superior to eruption as a method of dental age (DA) assessment. Eruption is only a brief occurrence, whereas formation may be related at different chronologic age levels, thereby providing a precise index for determining DA. The study was designed to determine the nature of inter relationship between chronologic and DA. MATERIALS AND METHODS: Age estimation depending upon tooth formation was done by Demirjian method and accuracy of Demirjian method was also evaluated. The sample for the study consisted of 197 children of Navi Mumbai. RESULTS: Significant positive correlation was found between chronologic age and DA that is, (r = 0.995), (P < 0.0001) for boys and (r = 0.995), (P < 0.0001) for girls. When age estimation was done by Demirjian method, mean the difference between true age (chronologic age) and assessed (DA) was 2 days for boys and 37 days for girls. Demirjian method showed high accuracy when applied to Navi Mumbai (Maharashtra - India) population. CONCLUSION: Demirjian method showed high accuracy when applied to Navi Mumbai (Maharashtra - India) population. PMID- 26381636 TI - Catalase and sodium fluoride mediated rehabilitation of enamel bleached with 37% hydrogen peroxide. AB - BACKGROUND: Bleaching agents bring about a range of unwanted changes in the physical structure of enamel which needs to be restored qualitatively and timely. Catalase being an antioxidant ensures the effective removal of free radicals and improvement in fluoride mediated remineralization from the enamel microstructure which if retained may harm the integrity and affect the hardness of enamel. MATERIALS AND METHODS: Thirty freshly extracted incisors were sectioned to 6 slabs which were divided into 5 groups: Group A, control; Group B, treatment with 37% hydrogen peroxide (HP); Group C, treatment with 37% HP and catalase, Group D, treatment with 37% HP and 5% sodium fluoride application, Group E, treatment with 37% HP followed by catalase and 5% sodium fluoride. Scanning electron microscope and microhardness analysis were done for all slabs. One-way ANOVA test was applied among different groups. RESULTS: Vicker's microhardness number (VHN) of Group B and C was significantly lower. No significant difference between VHN of Group B and C. VHN of Group D was significantly higher than Group A, B, and C; but significantly lower than Group E. VHN of Group E was significantly higher than any other experimental group. One-way ANOVA revealed a highly significant P value (P = 0.0001) and so Tukey's post-hoc Test for the group comparisons was employed. CONCLUSION: Subsequent treatment of bleached enamel with catalase and fluoride varnish separately results in repairing and significantly increasing the microhardness. PMID- 26381637 TI - Effect of conventional and sugar free pediatric syrup formulations on primary tooth enamel hardness: An in vitro study. AB - OBJECTIVES: To assess and compare the effect of conventional and sugar free pediatric syrup formulations on primary tooth enamel hardness over a period of 14 days. MATERIALS AND METHODS: An in vitro study was done on 40 noncarious deciduous teeth. 10 teeth in each group were dipped in 4 pediatric medicinal syrups (1 sugarfree and 3 conventional) for 1 min thrice daily for 14 days and the enamel surface micro hardness was checked at baseline, 7 th day and 14 th day by Vickers hardness testing machine. The pH, titratable acidity and buffering capacity of the syrups were assessed. RESULTS: The pH of syrups were above critical pH for demineralization of the tooth but tiratable acidity and buffering capacity differed. ANOVA test indicated that the reduction in mean micro hardness was maximum in Group D (Conventional Analgesic syrup) and least in Group A (Sugarfree cough syrup) on 7 th and 14 th day. On intergroup comparison there was no difference (P > 0.05) in micro hardness between Group B (Conventional Cough syrup) and Group C (Conventional Antibiotic). However, highly significant (P < 0.01) difference between the either pair of Group B with Group D, and Group C with Group D on 14 th day. The percentage reduction in micro hardness on 14 th day was maximum for Group D (24.4 +/- 2.2) and minimum for Group A (14.0 +/- 1.3) which was statistically significant (P < 0.01). CONCLUSION: Sugar free pediatric medicines can be effective in reducing dental erosion and efforts should be made to incorporate sugar substitutes in formulation of pediatric medicines. PMID- 26381638 TI - Central giant cell granuloma in a 4-year-old female child. AB - Central giant cell granulomas (CGCG) are reddish lesions of gingiva that account for an important number of disorders frequently diagnosed in the regular dental practice. Although the majority of the lesions are nonaggressive, asymptomatic, and slow-growing, about 30% show an aggressive, progressively destructive behavior, and a tendency to recur. We present a case of aggressive CGCG of the maxilla in a 4-year-old female child managed by surgical excision. To minimize the possible cost of esthetic, functional, and psychological problems, mainly in young patients, CGCG should be diagnosed and managed at the earliest. PMID- 26381639 TI - Treatment of skeletal class III malocclusion using face mask therapy with alternate rapid maxillary expansion and constriction (Alt-RAMEC) protocol. AB - Class III malocclusion is very common malocclusion and can be due to maxillary retrusion, mandibular prognathism, or combination. Ellis and McNamara found a combination of maxillary retrusion and mandibular protrusion to be the most common skeletal relationship (30%). The treatment should be carried out as early as possible for permitting normal growth of the skeletal bases. Reverse pull head gear combined with maxillary expansion can effectively correct skeletal Class III malocclusion due to maxillary deficiency in growing patient. An eight-year-old female patient with chief complaint of prognathic mandible and anterior crossbite was successfully treated in duration of 5 months with facemask and expansion therapy based on Alternate Rapid Maxillary Expansion and Constriction (Alt-RAMEC) protocol. PMID- 26381640 TI - Periostitis ossificans (Garre's osteomyelitis): An unusual case. AB - Garre's sclerosing osteomyelitis is a specific type of chronic osteomyelitis that mainly affects children and young adults and is commonly associated with odontogenic infection. The paper describes an unusual case of Garre's osteomyelitis in an 11-year-old boy, in whom the condition arose following poor oral hygiene and periodontal problems in relation to permanent mandibular left first molar. Clinically the patient presented with bony hard, nontender swelling and the occlusal radiograph revealed pathognomic feature of "onion skin" appearance. PMID- 26381641 TI - Oral, physical, and behavioral aspects of patient with chromosome 47, XYY syndrome. AB - Chromosome 47, XYY syndrome is usually diagnosed late. Some of the clinical characteristics of XYY syndrome may be perceptible in dental care. The slow development of cognitive and motor activities and tall stature is common in XYY patients. The aim of this article was to relate the oral, physical, and behavioral aspects of a 6-year-old patient with the chromosome 47, XYY syndrome, diagnosed by means of karyotyping. The patient presented motor difficulty, which led to a fall and traumatism in the anterior region. In the radiography, agenesia of the permanent maxillary lateral incisors, presence of taurodontism in the primary molars, and macrodontia of the maxillary central incisors and permanent molars could be observed. Once the diagnosis was made, it was possible to understand his difficulty at school, and make available appropriate monitoring by a suitable multidisciplinary team to stimulate, control, and minimize the day-to day difficulties found by patients with this syndrome. PMID- 26381642 TI - Congenital peripheral ameloblastic fibroma with intraosseous involvement in a 2 week-old infant: A case report with review of literature. AB - Ameloblastic fibroma is a rare, slow-growing benign mixed odontogenic tumor. It constitutes 2% of odontogenic tumors and is reported to occur at an age ranging from 6 months to 42 years. The youngest being a 7-week-old infant. We report a case of peripheral ameloblastic fibroma in a 2-week-old infant. The lesion presented since birth. It involved the maxilla with an extraosseous component involving the gingiva. A more or less conservative surgical approach of enucleation and curettage of the lesion was done under general anesthesia, trying to conserve the adjacent tooth buds. Only a few cases of congenital peripheral ameloblastic fibroma have been reported so far. PMID- 26381643 TI - Quality Improvement in Surgery Combining Lean Improvement Methods with Teamwork Training: A Controlled Before-After Study. AB - BACKGROUND: To investigate the effectiveness of combining teamwork training and lean process improvement, two distinct approaches to improving surgical safety. We conducted a controlled interrupted time series study in a specialist UK Orthopaedic hospital incorporating a plastic surgery team (which received the intervention) and an Orthopaedic theatre team acting as a control. STUDY DESIGN: We used a 3 month intervention with 3 months data collection period before and after it. A combined teamwork training and lean process improvement intervention was delivered by an experienced specialist team. Before and after the intervention we evaluated team non-technical skills using NOTECHS II, technical performance using the glitch rate and WHO checklist compliance using a simple 3 point scale. We recorded complication rate, readmission rate and length of hospital stay data for 6 months before and after the intervention. RESULTS: In the active group, but not the control group, full compliance with WHO Time Out (T/O) increased from 14 to 71% (p = 0.032), Sign Out attempt rate (S/O) increased from 0% to 50% (p<0.001) and Oxford NOTECHS II scores increased after the intervention (P = 0.058). Glitch rate decreased in the active group and increased in the control group (p = 0.001). Complications and length of stay appeared to rise in the control group and fall in the active group. CONCLUSIONS: Combining teamwork training and systems improvement enhanced both technical and non technical operating team process measures, and were associated with a trend to better safety outcome measures in a controlled study comparison. We suggest that approaches which address both system and culture dimensions of safety may prove valuable in reducing risks to patients. PMID- 26381646 TI - Medical Management and Trauma-Informed Care for Children in Foster Care. AB - Children enter foster care with a myriad of exposures and experiences, which can threaten their physical and mental health and development. Expanding evidence and evolving guidelines have helped to shape the care of these children over the past two decades. These guidelines address initial health screening, comprehensive medical evaluations, and follow-up care. Information exchange, attention to exposures, and consideration of how the adversities, which lead to foster placement, can impact health is crucial. These children should be examined with a trauma lens, so that the child, caregiver, and community supports can be assisted to view their physical and behavioral health from the perspective of what we now understand about the impact of toxic stress. Health care providers can impact the health of foster children by screening for the negative health consequences of trauma, advocating for trauma-informed services, and providing trauma-informed anticipatory guidance to foster parents. By taking an organized and comprehensive approach, the health care provider can best attend to the needs of this vulnerable population. PMID- 26381644 TI - A Novel Reading Scheme for Assessing the Extent of Radiographic Abnormalities and Its Association with Disease Severity in Sputum Smear-Positive Tuberculosis: An Observational Study in Hyderabad/India. AB - BACKGROUND: Existing reading schemes for chest X-ray (CXR) used to grade the extent of disease severity at diagnosis in patients with pulmonary tuberculosis (PTB) are often based on numerical scores that summate specific radiographic features. However, since PTB is known to exhibit a wide heterogeneity in pathology, certain features might be differentially associated with clinical parameters of disease severity. OBJECTIVE: We aimed to grade disease severity in PTB patients at diagnosis and after completion of DOTS treatment by developing a reading scheme based on five different radiographic manifestations and analyze their association with the clinical parameters of systemic involvement and infectivity. METHODS: 141 HIV-negative adults with newly diagnosed sputum smear positive PTB were enrolled in a prospective observational study in Hyderabad, India. The presence and extent on CXRs of five radiographic manifestations, i.e., lung involvement, alveolar infiltration, cavitation, lymphadenopathy and pleural effusion, were classified using the new reading scheme by using a four-quadrant approach. We evaluated the inter-reader reliability of each manifestation, and its association with BMI and sputum smear positivity at diagnosis. The presence and extent of these radiographic manifestations were further compared with CXRs on completion of DOTS treatment. RESULTS: At diagnosis, an average lung area of 51.7% +/- 23.3% was affected by radiographic abnormalities. 94% of the patients had alveolar infiltrates, with 89.4% located in the upper quadrants, suggesting post primary PTB and in 34.8% of patients cavities were found. We further showed that the extent of affected lung area was a negative predictor of BMI (beta value -0.035, p 0.019). No significant association of BMI with any of the other CXR features was found. The extent of alveolar infiltrates, along with the presence of cavitation, were strongly associated with sputum smear positivity. The microbiological cure rate in our cohort after 6 months of DOTS treatment was 95%. The extent of the affected lung area in these patients decreased from 56.0% +/- 21.5% to 31.0 +/- 20% and a decrease was also observed in the extent of alveolar infiltrates from 98.4% to 25.8% in at least one quadrant, presence of cavities from 34.8% to 1.6%, lymphadenopathy from 46.8% to 16.1%, and pleural effusion from 19.4% to 6.5%. CONCLUSIONS: We established a new assessment scheme for grading disease severity in PTB by specifically considering five radiographic manifestations which were differently associated with the BMI and sputum smear positivity, changed to a different extent after 6 months of treatment and exhibited an excellent agreement between radiologists. Our results suggest that this reading scheme might contribute to the estimation of disease severity with respect to differences in disease pathology. Further studies are needed to determine a correlation with short and long-term pulmonary function impairment and whether there would be any benefit in lengthening or modulating therapy based on this CXR severity assessment. PMID- 26381645 TI - Neurocognitive Impairments in Deficit and Non-Deficit Schizophrenia and Their Relationships with Symptom Dimensions and Other Clinical Variables. AB - BACKGROUND: Deficit schizophrenia (DS) has been proposed as a pathophysiologically distinct subgroup within schizophrenia. Earlier studies focusing on neurocognitive function of DS patients have yielded inconsistent findings ranging from substantial deficits to no significant difference relative to non-deficit schizophrenia patients (NDS). The present study investigated the severity and characteristic patterns of neurocognitive impairments in DS and NDS patients and their relationships with clinical variables. METHODS: Attention, ideation fluency, cognitive flexibility and visuospatial memory function were assessed in 40 DS patients, 57 NDS patients, and 52 healthy controls by a comprehensive neuropsychological battery. RESULTS: Both schizophrenia subgroups had overall more severe cognitive impairments than controls while DS performed worse on every neuropsychological measure except the Stroop interference than the NDS patients with age and education as the covariates. Profile analysis found significantly different patterns of cognitive profiles between two patients group mainly due to their differences in attention and cognitive flexibility functions. Age, education, illness duration and negative symptoms were found to have the correlations with cognitive impairments in the NDS group, while only age and the negative symptoms were correlated with the cognitive impairments in the DS group. Multiple regression analyses revealed that sustained attention and cognitive flexibility were the core impaired cognitive domains mediating other cognitive functions in DS and NDS patients respectively. CONCLUSIONS: DS patients exemplified worse in almost all cognitive domains than NDS patients. Sustained attention and cognitive flexibility might be the key impaired cognitive domains for DS and NDS patients respectively. The present study suggested the DS as a specific subgroup of schizophrenia. PMID- 26381647 TI - New insights into the genetic basis of natural chilling and cold shock tolerance in rice by genome-wide association analysis. AB - In order to understand cold adaptability and explore additional genetic resources for the cold tolerance improvement of rice, we investigated the genetic variation of 529 rice accessions under natural chilling and cold shock stress conditions at the seedling stage using genome-wide association studies; a total of 132 loci were identified. Among them, 12 loci were common for both chilling and cold shock tolerance, suggesting that rice has a distinct and overlapping genetic response and adaptation to the two stresses. Haplotype analysis of a known gene OsMYB2, which is involved in cold tolerance, revealed indica-japonica differentiation and latitude tendency for the haplotypes of this gene. By checking the subpopulation and geographical distribution of accessions with tolerance or sensitivity under these two stress conditions, we found that the chilling tolerance group, which mainly consisted of japonica accessions, has a wider latitudinal distribution than the chilling sensitivity group. We conclude that the genetic basis of natural chilling stress tolerance in rice is distinct from that of cold shock stress frequently used for low-temperature treatment in the laboratory and the cold adaptability of rice is associated with the subpopulation and latitudinal distribution. PMID- 26381648 TI - Detection of beta-exotoxin synthesis in Bacillus thuringiensis using an easy bioassay with the nematode Caenorhabditis elegans. AB - The insecticidal activity of Bacillus thuringiensis is owing to the action of Cry and Cyt proteins. In addition to the synthesis of insecticidal proteins, some strains are able to synthesize beta-exotoxin, which is highly toxic to humans. In this regard, it is very important to have a simple method to detect beta-exotoxin to avoid the commercial production of this type of strains. In this work, we developed a simple and fast method, using the nematode Caenorhabditis elegans to detect indirectly the synthesis of beta-exotoxin by B. thuringiensis strain. Using this assay, we detected that ~60% of Mexican native strains (i.e. LBIT-471, 491, 492, 497, 507, 511, 515, 536 and 537) were toxic to the nematode (44-97% mortalities) and their beta-exotoxin (betaEx(+) ) production, including a positive control (NRD-12), was confirmed by HPLC. In addition, the negative controls (betaEx(-) ) LBIT-436 (HD-1) and LBIT-438 and also the native strains LBIT-499, 500, 521, 522, 533 and 542, did not show a detrimental effect against nematodes larvae, neither the synthesis of beta-exotoxin as determined by HPLC. Finally, we did not find a correlation between B. thuringiensis strains with similar plasmid patterns and the beta-exotoxin production. SIGNIFICANCE AND IMPACT OF THE STUDY: In this work, we implemented a qualitative and fast bioassay using the nematode Caenorhabditis elegans to detect the production of beta exotoxin in different strains of Bacillus thuringiensis. We show that this assay is useful to detect beta-exotoxin in B. thuringiensis with high reliability, helping to discriminate strains that could not be used as bioinsecticides because of their putative risk to humans. Data show that qualitative bioassay with nematodes is a potential alternative to fly larvae bioassays, and correlated with the determination of beta-exotoxin by HPLC. PMID- 26381649 TI - Inferring Protective CD8+ T-Cell Epitopes for NS5 Protein of Four Serotypes of Dengue Virus Chinese Isolates Based on HLA-A, -B and -C Allelic Distribution: Implications for Epitope-Based Universal Vaccine Design. AB - Dengue is one of the most globally serious vector-borne infectious diseases in tropical and subtropical areas for which there are currently no effective vaccines. The most highly conserved flavivirus protein, NS5, is an indispensable target of CD8+ T-cells, making it an ideal vaccine design target. Using the Immune Epitope Database (IEDB), CD8+ T-cell epitopes of the dengue virus (DENV) NS5 protein were predicted by genotypic frequency of the HLA-A,-B, and-C alleles in Chinese population. Antigenicity scores of all predicted epitopes were analyzed using VaxiJen v2.0. The IEDB analysis revealed that 116 antigenic epitopes for HLA-A (21),-B (53), and-C (42) had high affinity for HLA molecules. Of them, 14 had 90.97-99.35% conversancy among the four serotypes. Moreover, five candidate epitopes, including 200NS5210 (94.84%, A*11:01), 515NS5525 (98.71%, A*24:02), 225NS5232 (99.35%, A*33:03), 516NS5523 (98.71%, A*33:03), and 284NS5291 (98.06%, A*33:03), were presented by HLA-A. Four candidate epitopes, including 234NS5241 (96.77%, B*13:01), 92NS599 (98.06%, B*15:01, B*15:02, and B*46:01), 262NS5269 (92.90%, B*38:02), and 538NS5547 (90.97%, B*51:01), were presented by HLA-B. Another 9 candidate epitopes, including 514NS5522 (98.71%, C*01:02), 514NS5524 (98.71%, C*01:02 and C*14:02), 92NS599 (98.06%, C*03:02 and C*15:02), 362NS5369 (44.84%, C*03:04 and C*08:01), 225NS5232 (99.35%, C*04:01), 234NS5241(96.77%, C*04:01), 361NS5369 (94.84%, C*04:01), 515NS5522 (98.71%, C*14:02), 515NS5524 (98.71%, C*14:02), were presented by HLA-C. Further data showed that the four-epitope combination of 92NS599 (B*15:01, B*15:02, B*46:01, C*03:02 and C*15:02), 200NS5210 (A*11:01), 362NS5369 (C*03:04, C*08:01), and 514NS5524 (C*01:02, C*14:02) could vaccinate >90% of individuals in China. Further in vivo study of our inferred novel epitopes will be needed for a T-cell epitope-based universal vaccine development that may prevent all four China endemic DENV serotypes. PMID- 26381650 TI - Impact of incarceration experiences on reported HIV status and associated risk behaviours and disease comorbidities. AB - BACKGROUND: The Russian human immunodeficiency virus (HIV) epidemic among people who inject drugs (PWID) originated in Kaliningrad, but research into risk behaviours among PWID has been lacking. The potential for heterosexual spread has not been analysed. METHODS: A sample of PWID was accrued using two methods. A questionnaire was administered to assess HIV-related risk behaviours for parenteral and sexual transmission, sociodemographic factors, HIV knowledge and attitudes about sexual risks. Data were analysed focusing on the role of imprisonment, factors associated with awareness of being HIV infected and condom use. RESULTS: More than a quarter of the sample reported having been diagnosed with HIV infection, with higher prevalence among women and those with a history of incarceration. More than half reported having been diagnosed with hepatitis C virus infection. Those reporting being HIV positive were less likely to distribute used syringes to other PWID and more likely to have used a condom the last time they had sex. A history of incarceration was associated with higher rates of receptive syringe sharing among those not having ever received an HIV positive diagnosis and a lower likelihood of believing that condoms are needed when having sex with a casual partner. CONCLUSION: Although extensive HIV testing has alerted many PWID to their HIV-positive status, which is associated with less distributive syringe sharing and higher likelihood of condom use, substantial risk for parenteral and especially sexual HIV transmission remains. More active prevention programs will be required to control the heterosexual spread of HIV. PMID- 26381652 TI - Fabrication and Characterization of a Conformal Skin-like Electronic System for Quantitative, Cutaneous Wound Management. AB - Recent advances in the development of electronic technologies and biomedical devices offer opportunities for non-invasive, quantitative assessment of cutaneous wound healing on the skin. Existing methods, however, still rely on visual inspections through various microscopic tools and devices that normally include high-cost, sophisticated systems and require well trained personnel for operation and data analysis. Here, we describe methods and protocols to fabricate a conformal, skin-like electronics system that enables conformal lamination to the skin surface near the wound tissues, which provides recording of high fidelity electrical signals such as skin temperature and thermal conductivity. The methods of device fabrication provide details of step-by-step preparation of the microelectronic system that is completely enclosed with elastomeric silicone materials to offer electrical isolation. The experimental study presents multifunctional, biocompatible, waterproof, reusable, and flexible/stretchable characteristics of the device for clinical applications. Protocols of clinical testing provide an overview and sequential process of cleaning, testing setup, system operation, and data acquisition with the skin-like electronics, gently mounted on hypersensitive, cutaneous wound and contralateral tissues on patients. PMID- 26381651 TI - Derepression of Mineral Phosphate Solubilization Phenotype by Insertional Inactivation of iclR in Klebsiella pneumoniae. AB - The mode of succinate mediated repression of mineral phosphate solubilization and the role of repressor in suppressing phosphate solubilization phenotype of two free-living nitrogen fixing Klebsiella pneumoniae strains was studied. Organic acid mediated mineral phosphate solubilization phenotype of oxalic acid producing Klebsiella pneumoniae SM6 and SM11 were transcriptionally repressed by IclR in presence of succinate as carbon source. Oxalic acid production and expression of genes of the glyoxylate shunt (aceBAK) was found only in glucose but not in succinate- and glucose+succinate-grown cells. IclR, repressor of aceBAK operon, was inactivated using an allelic exchange system resulting in derepressed mineral phosphate solubilization phenotype through constitutive expression of the glyoxylate shunt. Insertional inactivation of iclR resulted in increased activity of the glyoxylate shunt enzymes even in succinate-grown cells. An augmented phosphate solubilization up to 54 and 59% soluble phosphate release was attained in glucose+succinate-grown SM6Delta and SM11Delta strains respectively, compared to glucose-grown cells, whereas phosphate solubilization was absent or negligible in wildtype cells grown in glucose+succinate. Both wildtype and iclR deletion strains showed similar indole-3-acetic acid production. Wheat seeds inoculated with wildtype SM6 and SM11 improved both root and shoot length by 1.2 fold. However, iclR deletion SM6Delta and SM11Delta strains increased root and shoot length by 1.5 and 1.4 folds, respectively, compared to uninoculated controls. The repressor inactivated phosphate solubilizers better served the purpose of constitutive phosphate solubilization in pot experiments, where presence of other carbon sources (e.g., succinate) might repress mineral phosphate solubilization phenotype of wildtype strains. PMID- 26381653 TI - IgG4-related stomach muscle lesion with a renal pseudotumor and multiple renal rim-like lesions: A rare manifestation of IgG4-related disease. AB - We describe a 74-year-old man with immunoglobulin G4-related disease (IgG4-RD) presenting with gastric cancer, stomach and kidney lesions. For 15 years, the patient had been treated under a diagnosis of sclerosing cholangitis, which was revealed to be IgG4-RD only when the cancer was found. Histology revealed the gastric cancer and IgG4-related lesion in the muscularis propria to be separate. This case suggests that the stomach muscle can also be a site of involvement of IgG4-RD. PMID- 26381654 TI - Nitric Oxide and Hydrogen Sulfide Regulation of Ischemic Vascular Remodeling. AB - Blockage or restriction of blood flow through conduit arteries results in tissue ischemia downstream of the disturbed area. Local tissues can adapt to this challenge by stimulating vascular remodeling through angiogenesis and arteriogenesis thereby restoring blood perfusion and removal of wastes. Multiple molecular mechanisms of vascular remodeling during ischemia have been identified and extensively studied. However, therapeutic benefits from these findings and insights are limited due to the complexity of various signaling networks and a lack of understanding central metabolic regulators governing these responses. The gasotransmitters NO and H2 S have emerged as master regulators that influence multiple molecular targets necessary for ischemic vascular remodeling. In this review, we discuss how NO and H2 S are individually regulated under ischemia, what their roles are in angiogenesis and arteriogenesis, and how their interaction controls ischemic vascular remodeling. PMID- 26381656 TI - Cardioprotective role of tadalafil against cisplatin-induced cardiovascular damage in rats. AB - The present study investigated the possible cardioprotective effect of tadalafil (Tad) on cisplatin (CDDP)-induced cardiac and vascular damages in rats. A total number of seventy two healthy male albino rats initially weighting between 200 and 220 g were used and randomly divided into four groups,18 rats in each. The control group received no treatment; CDDP group received a single dose of CDDP (4 mg/kg) intraperitoneal (i.p.) per week for 4 weeks the duration of the experiment; Tad group received 0.4 mg/kg BW Tad i.p. daily and Tad +CDDP group received 0.4 mg/kg BW Tad i.p. +4 mg/kg BW CDDP i.p. The results showed that Tad was able to decrease blood pressure, heart rate, levels of serum cardiac troponin (cTn-I), malondialdehyde (MDA) and increased levels of reduced glutathione (GSH) and nitric oxide (NO) in the heart homogenate sample from CDDP treated rats. Semi quantitative analysis showed that Tad was able to decrease the histopathological scores of cardiac muscular hyalinzation and fibrosis in three sacrifices in CDDP treated rats. CDDP treated rats showed significantly increased thickening in wall of aorta with an irregular luminal layer of endothelial cell linings in three sacrifices when it was compared to other groups. Moreover, immunohistochemical labeling of alpha- smooth muscle actin (alpha-SMA) in aorta revealed significant lower scores in Tad +CDDP group when they were compared to CDDP group. In conclusion, Tad alone did not induce any harmful effects on blood pressure, selective antioxidant, peroxidation markers or cardiac histology, in addition, Tad has a cardio-protective role against CDDP. PMID- 26381655 TI - Proteomics of Aggregatibacter actinomycetemcomitans Outer Membrane Vesicles. AB - Aggregatibacter actinomycetemcomitans is an oral and systemic pathogen associated with aggressive forms of periodontitis and with endocarditis. Outer membrane vesicles (OMVs) released by this species have been demonstrated to deliver effector proteins such as cytolethal distending toxin (CDT) and leukotoxin (LtxA) into human host cells and to act as triggers of innate immunity upon carriage of NOD1- and NOD2-active pathogen-associated molecular patterns (PAMPs). To improve our understanding of the pathogenicity-associated functions that A. actinomycetemcomitans exports via OMVs, we studied the proteome of density gradient-purified OMVs from a rough-colony type clinical isolate, strain 173 (serotype e) using liquid chromatography-tandem mass spectrometry (LC-MS/MS). This analysis yielded the identification of 151 proteins, which were found in at least three out of four independent experiments. Data are available via ProteomeXchange with identifier PXD002509. Through this study, we not only confirmed the vesicle-associated release of LtxA, and the presence of proteins, which are known to act as immunoreactive antigens in the human host, but we also identified numerous additional putative virulence-related proteins in the A. actinomycetemcomitans OMV proteome. The known and putative functions of these proteins include immune evasion, drug targeting, and iron/nutrient acquisition. In summary, our findings are consistent with an OMV-associated proteome that exhibits several offensive and defensive functions, and they provide a comprehensive basis to further disclose roles of A. actinomycetemcomitans OMVs in periodontal and systemic disease. PMID- 26381657 TI - Excipients in Oral Antihistamines Can Perpetuate Allergic Contact Dermatitis. AB - Propylene glycol is a well-documented causative agent of allergic contact dermatitis (ACD). It is also reported to cause systemic dermatitis after ingestion of foods or medicines containing it and after intravenous injection of a medicine with propylene glycol in its base. We describe two adolescents with sensitivity to propylene glycol confirmed by patch testing whose dermatitis improved dramatically after cessation of oral antihistamines containing propylene glycol. We report these cases to alert providers to the potential for worsening of ACD due to systemic exposure to propylene glycol in patients with a cutaneous sensitivity to the allergen. PMID- 26381659 TI - Short-term follow-up in 6 months is unnecessary for asymptomatic breast lesions with benign concordant results obtained at ultrasonography-guided 14-gauge core needle biopsy. AB - BACKGROUND: We investigated whether short-term follow-up in 6 months was appropriate for asymptomatic benign concordant lesions on ultrasonography-guided core needle biopsy (ultrasonography-guided CNB). METHODS: Of 1,111 lesions, 944 underwent follow-up within 4 to 9 months after CNB, and 359 of 944 underwent a 2nd follow-up within 9 to 15 months. One hundred sixty-seven underwent a 1st follow-up within 9 to 15 months. Follow-up intervals were classified according to an interval of 6 and 12 months with 2 different methods. First, 944 and 167 lesions were classified into the 6- and 12-month groups. Second, 944 and 526 lesions (sum of 167 and 359 lesions) were classified into the 6- and 12-month groups. Clinicopathologic factors were compared between the 2 groups. RESULTS: None of the benign concordant lesions were malignant; 1.4% of the lesions showed progression in the 6-month group, not significantly different from 1.2% and .8% of the 12-month group. Mean age, mean lesion size, final assessments, and specific or nonspecific pathologies were not different between the 2 groups. CONCLUSIONS: Short-term follow-up in 6 months is unnecessary for asymptomatic benign concordant breast lesions at ultrasonography-guided CNB. PMID- 26381658 TI - Magnetic resonance neurography detects diabetic neuropathy early and with Proximal Predominance. AB - OBJECTIVE: The aim of this work was to localize and quantify alterations of nerve microstructure in diabetic polyneuropathy (DPN) by magnetic resonance (MR) neurography with large anatomical coverage. METHODS: Patients (N = 25) with mild to-moderate (Neuropathy-Symptom-Score [NSS]/Neuropathy Deficit Score [NDS] 3.8 +/ 0.3/2.6 +/- 0.5) and patients (n = 10) with severe DPN (6.2 +/- 0.6/7.4 +/- 0.5) were compared to patients (n = 15) with diabetes but no DPN and to age-/sex matched nondiabetic controls (n = 25). All subjects underwent MR neurography with large spatial coverage and high resolution from spinal nerve to ankle level: four slabs per leg, each with 35 axial slices (T2- and proton-density-weighted two dimensional turbo-spin-echo sequences; voxel size: 0.4 * 0.3 * 3.5 mm(3) ) and a three-dimensional T2-weighted sequence to cover spinal nerves and plexus. Nerve segmentation was performed on a total of 280 slices per subject. Nerve lesion voxels were determined independently from operator input by statistical classification against the nondiabetic cohort. At the site with highest lesion voxel burden, signal quantification was performed by calculating nerve proton spin density and T2 relaxation time. RESULTS: Total burden of nerve lesion voxels was significantly increased in DPN (p = 0.003) with strong spatial predominance at thigh level, where average lesion voxel load was significantly higher in severe (57 +/- 18.4; p = 0.0022) and in mild-to-moderate DPN (35 +/- 4.0; p < 0.001) than in controls (18 +/- 3.6). Signal quantification at the site of predominant lesion burden (thigh) revealed a significant increase of nerve proton spin density in severe (360 +/- 22.9; p = 0.043) and in mild-to-moderate DPN (365 +/- 15.2; p = 0.001) versus controls (288 +/- 13.4), but not of T2 relaxation time (p = 0.49). Nerve proton spin density predicted severity of DPN with an odds ratio of 2.9 (95% confidence interval: 2.4-3.5; p < 0.001) per 100 proton spins. INTERPRETATION: In DPN, the predominant site of microstructural nerve alteration is at the thigh level with a strong proximal-to-distal gradient. Nerve proton spin density at the thigh level is a novel quantitative imaging biomarker of early DPN and increases with neuropathy severity. PMID- 26381660 TI - Angiogenesis Markers in Gynecological Tumors and Patents for Anti-Angiogenic Approach: Review. AB - The formation of a tumor-associated vascular network is an important step in understanding the stages of tumor progression. This review aims to highlight the main markers of induction, proliferation and inhibition of angiogenesis, as well as the quantification of microvessel density, correlated with preclinical and clinical research in gynecologic cancers and also discussed related patents. Studies show that in the most advanced cases of gynecological cancers, biomarkers such as VEGF (Vascular Endothelial Growth Factor), MMP (Matrix Metalloproteinase), CD105 (Endoglin), TIMP (tissue inhibitors of metalloproteinases) and VASH (Vasohibin) are more expressed compared to healthy individuals. Continuous evaluation of these biomarkers in cancer cases could serve in the future as a basis for development of new therapeutic approaches, leading to a good response to cancer treatment, and thus increase survival of cancer patients. PMID- 26381661 TI - Optimization of culture conditions for Gardnerella vaginalis biofilm formation. AB - Bacterial vaginosis is the leading vaginal disorder in women in reproductive age. Although bacterial vaginosis is related with presence of a biofilm composed predominantly by Gardnerella vaginalis, there has not been a detailed information addressing the environmental conditions that influence the biofilm formation of this bacterial species. Here, we evaluated the influence of some common culture conditions on G. vaginalis biofilm formation, namely inoculum concentration, incubation period, feeding conditions and culture medium composition. Our results showed that culture conditions strongly influenced G. vaginalis biofilm formation and that biofilm formation was enhanced when starting the culture with a higher inoculum, using a fed-batch system and supplementing the growth medium with maltose. PMID- 26381662 TI - Species identification within Acinetobacter calcoaceticus-baumannii complex using MALDI-TOF MS. AB - Acinetobacter baumannii, one of the more clinically relevant species in the Acinetobacter genus is well known to be multi-drug resistant and associated with bacteremia, urinary tract infection, pneumonia, wound infection and meningitis. However, it cannot be differentiated from closely related species such as Acinetobacter calcoaceticus, Acinetobacter pittii and Acinetobacter nosocomialis by most phenotypic tests and can only be differentiated by specific, time consuming genotypic tests with very limited use in clinical microbiological laboratories. As a result, these species are grouped into the A. calcoaceticus-A. baumannii (Acb) complex. Herein we investigated the mass spectra of 73 Acinetobacter spp., representing ten different species, using an AB SCIEX 5800 MALDI-TOF MS to differentiate members of the Acinetobacter genus, including the species of the Acb complex. RpoB gene sequencing, 16S rRNA sequencing, and gyrB multiplex PCR were also evaluated as orthogonal methods to identify the organisms used in this study. We found that whilst 16S rRNA and rpoB gene sequencing could not differentiate A. pittii or A. calcoaceticus, they can be differentiated using gyrB multiplex PCR and MALDI-TOF MS. All ten Acinetobacter species investigated could be differentiated by their MALDI-TOF mass spectra. PMID- 26381663 TI - Development and evaluation of immunochromatography to detect Gram-negative bacteria producing ArmA 16S rRNA methylase responsible for aminoglycoside resistance. AB - Rapid and reliable detection of aminoglycoside-resistant bacteria is an important infection-control measure and a crucial aspect of antimicrobial chemotherapy. The enzyme 16S rRNA methylase has been shown to mediate aminoglycoside resistance in bacteria. This study describes a newly developed immunochromatographic assay using novel monoclonal antibodies (mAbs) that recognize ArmA 16S rRNA methylase. Epitope mapping showed that these mAbs recognized amino acids 1-93 of ArmA, which consists of 257 amino acids. Evaluation of the assay using ArmA producing and non producing bacterial species, as well as bacteria producing other types of 16S rRNA methylases, indicated that immunochromatographic detection of the ArmA-type 16S rRNA methylase was fully consistent with PCR analysis for armA genes, with all immunochromatographically positive strains being resistant to aminoglycosides (MIC>=128MUg/mL). The detection limit of the assay was 12ng ArmA. These findings indicate that this assay can be used for the rapid and reliable detection of the production of ArmA 16S rRNA methylase by Gram-negative bacteria, including Acinetobacter baumannii and Escherichia coli. PMID- 26381664 TI - Engineering versatile protein expression systems mediated by inteins in Escherichia coli. AB - We have recently employed an intein, Saccharomyces cerevisiae vascular membrane ATPase (VMA), in conjunction with efficient expression and secretory functions formed between the ompA leader sequence and the human epidermal growth factor (EGF) gene (fused at the 5' end of VMA), and the human basic fibroblast growth factor (bFGF) gene (fused at the 3' end of VMA), to engineer an efficient intein based Escherichia coli system for high-level co-expression of EGF and bFGF as authentic mature products. Both products were found not only excreted to the culture medium but also located, surprisingly, in the cytoplasm (Kwong and Wong 2013). In this study, we employed two structurally varied inteins, VMA and Mycobacterium xenopi GyraseA (GyrA), and further demonstrated that despite acting alone, both VMA and GyrA were able to mediate successful co-expression of two widely different proteins, EGF and an endoglucanase (Eng) in E. coli. Although EGF and Eng were initially expressed as large precursors/intermediates, they were soluble and auto-cleavable to finally yield the desired products in both the cytoplasm and culture media. The results further substantiate our postulation that the aforementioned intein/E. coli approach might lead to the development of cost-effective and versatile host systems, wherein all culture fractions are involved in producing the target proteins. PMID- 26381665 TI - Role of extracellular polymeric substances (EPS) production in bioaggregation: application to wastewater treatment. AB - This paper reviews the formation, structure, and stability of bioaggregates with an emphasis on the composition and distribution of extracellular polymeric substances (EPS) and their role in bioaggregation. Bioaggregation is ubiquitous in natural environment and is of great importance in biological wastewater treatment processes. It greatly influences the flocculability, settleability, and dewaterability for flocs and sludge retention and shear resistance for biofilms. The physico-chemical and microbial structures of bioaggregates are dependent on operational conditions as well as microbial diversity and spatial distribution. The formation of bioaggregates is mediated by the physico-chemical interactions as well as the microbial interactions such as EPS production and quorum sensing. EPS are composed of a mixture of macromolecules including proteins, polysaccharides, humic-like substances, and nucleic acids, which entrap the microbial cells in a three-dimensional matrix. The composition and physico chemical characteristics of EPS have significant influence on the maintenance of the bioaggregate structure and the process performance of the wastewater treatment. However, the mechanisms of bioaggregation are still unclear and the conclusions on the role of EPS were mostly drawn from the established correlations and hypotheses. This paper expects to provide up-to-date knowledge on bioaggregation and insights for further studies and applications. PMID- 26381666 TI - The influence of bisphenol A on mammalian cell cultivation. AB - Bisphenol A (BPA) plays a substantial role in industry, as it is used for polycarbonate (PC) plastics and epoxy resins which are required for various plastic consumer products. However, BPA is known to be an endocrine disruptor, and its influence on humans, animals, and various cell lines was addressed in diverse studies. As the burden of BPA can be increased by using disposable plastic articles and single-use technologies for cultivation, it is essential to examine the consequences of BPA presence on mammalian cells, as they are a contributing factor in the production of complex pharmaceutical therapeutics. We selected three industrially relevant cell lines and analyzed systemic effects of BPA by comparing cell culture performance in BPA-free poly-ethylene terephthalate glycol (PETG) and in PC shaking flasks. We focused on the influence of BPA on cellular growth, viability, and several metabolic parameters. In addition, we determined the product concentration and aggregation behavior of the recombinant proteins expressed by these cell lines and the BPA concentration within the medium caused by leaching. Moreover, we performed EC50 studies to determine the toxic concentration of BPA. Our results indicated that leached BPA had no effect on specific growth rates and viability and toxicity appeared at about 10(4) times higher concentrations; however, it influenced the specific productivity rate and metabolic activity parameters of our Chinese hamster ovary (CHO) cell line. Consequently, one can neglect BPA from leaching in the culture as long as the selected cell line is BPA tolerant. Otherwise, BPA can be a hurdle for pharmaceutical production, as it can influence the specific productivity of recombinant proteins. PMID- 26381667 TI - Anacardic acid induces apoptosis-like cell death in the rice blast fungus Magnaporthe oryzae. AB - Anacardic acid (6-pentadecylsalicylic acid), extracted from cashew nut shell liquid, is a natural phenolic lipid well known for its strong antibacterial, antioxidant, and anticancer activities. Its effect has been well studied in bacterial and mammalian systems but remains largely unexplored in fungi. The present study identifies antifungal, cytotoxic, and antioxidant activities of anacardic acid in the rice blast fungus Magnaporthe oryzae. It was found that anacardic acid causes inhibition of conidial germination and mycelial growth in this ascomycetous fungus. Phosphatidylserine externalization, chromatin condensation, DNA degradation, and loss of mitochondrial membrane potential suggest that growth inhibition of fungus is mainly caused by apoptosis-like cell death. Broad-spectrum caspase inhibitor Z-VAD-FMK treatment indicated that anacardic acid induces caspase-independent apoptosis in M. oryzae. Expression of a predicted ortholog of apoptosis-inducing factor (AIF) was upregulated during the process of apoptosis, suggesting the possibility of mitochondria dependent apoptosis via activation of apoptosis-inducing factor. Anacardic acid treatment leads to decrease in reactive oxygen species rather than increase in reactive oxygen species (ROS) accumulation normally observed during apoptosis, confirming the antioxidant properties of anacardic acid as suggested by earlier reports. Our study also shows that anacardic acid renders the fungus highly sensitive to DNA damaging agents like ethyl methanesulfonate (EMS). Treatment of rice leaves with anacardic acid prevents M. oryzae from infecting the plant without affecting the leaf, suggesting that anacardic acid can be an effective antifungal agent. PMID- 26381668 TI - The influence of voltage applied between the electrodes on optical and morphological properties of the InGaN thin films grown by thermionic vacuum arc. AB - The aim of this research is to investigate the optical and morphological properties of the InGaN thin films deposited onto amorphous glass substrates in two separate experiments with two different voltages applied between the electrodes, i.e. 500 and 600 V by means of the thermionic vacuum arc technique. This technique is original for thin film deposition and it enables thin film production in a very short period of time. The optical and morphological properties of the films were investigated by using field emission scanning electron microscope, atomic force microscope, spectroscopic ellipsometer, reflectometer, spectrophotometer, and optical tensiometer. Optical properties were also supported by empirical relations. The deposition rates were calculated as 3 and 3.3 nm/sec for 500 and 600 V, respectively. The increase in the voltage also increased the refractive index, grain size, root mean square roughness and surface free energy. According to the results of the wetting experiments, InGaN samples were low-wettable, also known as hydrophobic. PMID- 26381669 TI - Direct Dual-Template Synthesis of MWW Zeolite Monolayers. AB - A two-dimensional zeolite with the topology of MWW sheets has been obtained by direct synthesis with a combination of two organic structure-directing agents. The resultant material consists of approximately 70% single and double layers and displays a well-structured external surface area of about 300 m(2) g(-1). The delaminated zeolite prepared by means of this single-step synthetic route has a high delamination degree, and the structural integrity of the MWW layers is well preserved. The new zeolite material displayed excellent activity, selectivity, and stability when used as a catalyst for the alkylation of benzene with propylene and found to be superior to the catalysts that are currently used for producing cumene. PMID- 26381670 TI - Comment on "The complete nucleotide sequence and genome organization of pea streak virus (genus Carlavirus)". PMID- 26381671 TI - Osteochondral autografts. AB - The healing potential for articular cartilage lesions is limited due to many physiological, local and mechanical factors. Spontaneous healing of partial- and full-thickness lesions is slow, and subsequent tissue response is usually not durable. In symptomatic, and high-demand, patients, a definitive treatment modality must be offered which allows for a sustained recovery with minimal debilitation. Injuries, which damage the subchondral bone, heal with the formation of fibrocartilage. This tissue fails long-term survival because of its inability to withstand the variable cyclic loads and compression forces that it is subjected to. While regeneration of the damaged cartilage by an entirely new articular surface is a goal beyond current available techniques, repair of the osteochondral defects with normal hyaline cartilage is possible by various options. Osteochondral defects that are larger then 2 cm are best treated by osteochondral autograft technique. The short-term outcomes of the present series show excellent results. PMID- 26381672 TI - Dynamic Measurement of Tumor Vascular Permeability and Perfusion using a Hybrid System for Simultaneous Magnetic Resonance and Fluorescence Imaging. AB - PURPOSE: Assessing tumor vascular features including permeability and perfusion is essential for diagnostic and therapeutic purposes. The aim of this study was to compare fluorescence and magnetic resonance imaging (MRI)-based vascular readouts in subcutaneously implanted tumors in mice by simultaneous dynamic measurement of tracer uptake using a hybrid fluorescence molecular tomography (FMT)/MRI system. PROCEDURE: Vascular permeability was measured using a mixture of extravascular imaging agents, GdDOTA and the dye Cy5.5, and perfusion using a mixture of intravascular agents, Endorem and a fluorescent probe (Angiosense). Dynamic fluorescence reflectance imaging (dFRI) was integrated into the hybrid system for high temporal resolution. RESULTS: Excellent correspondence between uptake curves of Cy5.5/GdDOTA and Endorem/Angiosense has been found with correlation coefficients R > 0.98. The two modalities revealed good agreement regarding permeability coefficients and centers-of-gravity of the imaging agent distribution. CONCLUSION: The FMT/dFRI protocol presented is able to accurately map physiological processes and poses an attractive alternative to MRI for characterizing tumor neoangiogenesis. PMID- 26381673 TI - Day case surgery: not the whole answer to the NHS's increasing demand for operations. PMID- 26381674 TI - Chlamydia trachomatis utilizes the mammalian CLA1 lipid transporter to acquire host phosphatidylcholine essential for growth. AB - Phosphatidylcholine is a constituent of Chlamydia trachomatis membranes that must be acquired from its mammalian host to support bacterial proliferation. The CLA1 (SR-B1) receptor is a bi-directional phosphatidylcholine/cholesterol transporter that is recruited to the inclusion of Chlamydia-infected cells along with ABCA1. C. trachomatis growth was inhibited in a dose-dependent manner by BLT-1, a selective inhibitor of CLA1 function. Expression of a BLT-1-insensitive CLA1(C384S) mutant ameliorated the effect of the drug on chlamydial growth. CLA1 knockdown using shRNAs corroborated an important role for CLA1 in the growth of C. trachomatis. Trafficking of a fluorescent phosphatidylcholine analogue to Chlamydia was blocked by the inhibition of CLA1 or ABCA1 function, indicating a critical role for these transporters in phosphatidylcholine acquisition by this organism. Our analyses using a dual-labelled fluorescent phosphatidylcholine analogue and mass spectrometry showed that the phosphatidylcholine associated with isolated Chlamydia was unmodified host phosphatidylcholine. These results indicate that C. trachomatis co-opts host phospholipid transporters normally used to assemble lipoproteins to acquire host phosphatidylcholine essential for growth. PMID- 26381675 TI - Fatal Disseminated Toxoplasma gondii Infection in a Captive Harbour Porpoise (Phocoena phocoena). AB - A 7-year-old female harbour porpoise (Phocoena phocoena), born and held in captivity, suffered from reduced consciousness, imprecise and circling swimming movements and long phases of immobility over a period of 3 weeks. The animal died during treatment in a Danish open sea facility. Pathological examination revealed multifocal pyogranulomatous to necrotizing meningoencephalomyelitis, ganglioneuritis, plexus chorioiditis, myocarditis, hepatitis and adrenalitis with few intralesional protozoal tachyzoites and bradyzoites within cysts. Immunohistochemistry was positive for Toxoplasma gondii antigen within the lesions. Using polymerase chain reaction (PCR), the presence of T. gondii specific genome fragments was confirmed. A multilocus PCR-restriction fragment length polymorphism analysis using nine unlinked marker regions (nSAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1 and Apico) resulted in the identification of T. gondii type II (variant Apico Type I), which is the T. gondii genotype dominating in Germany. This is the first description of disseminated fatal toxoplasmosis in a captive harbour porpoise that lived in an open sea basin. Surface water contaminated with toxoplasma oocysts is regarded as the most likely source of infection. PMID- 26381676 TI - Nasopharyngeal mass filling the choanae revealing sarcoidosis. PMID- 26381677 TI - Unusual site of organized haematoma in a context of chronic myeloid leukaemia. PMID- 26381678 TI - Traumatic tracheal injury in a child. PMID- 26381679 TI - Bilateral extraskeletal chondroma of the neck. PMID- 26381680 TI - Virtual courses: enhancing a curriculum. AB - INTRODUCTION: Providers of education programmes are required to demonstrate to students, staff and external regulators the content of the programme and how this aligns to key outcomes. Whilst many programme themes are straightforward to illustrate, other integral themes prove challenging to demonstrate independently. INNOVATION: A virtual course takes elements within the current programme relating to a specific theme, repackages and maps them to provide clear signposting by highlighting each occasion the theme is taught, experienced and assessed. The individual elements remain within their current course, so there is no disruption to the established curriculum, but there is an enhancement in terms of transparently displaying linkages within a theme. DISCUSSION: Using the concept of virtual courses we have found we can respond to new initiatives and requirements of external regulators, as well as providing improved signposting for staff and students. This can be undertaken without the need to redesign a whole curriculum. CONCLUSION: In well-designed and currently effective curricula, we would like to recommend that virtual course development can enhance programme transparency, demonstrate external regulatory requirements and promote quality assurance without disruption to current content. PMID- 26381681 TI - Treatment of bacterial skin infections in ED observation units: factors influencing prescribing practice. AB - OBJECTIVE: The Infectious Disease Society of America (IDSA) publishes evidence based guidelines for the treatment of skin and soft tissue infections. How closely physicians follow these guidelines is unknown, particularly in the emergency department observation unit (EDOU) where increasing numbers of patients are treatment for these infections. Our objectives were to describe (1) the antibiotic treatment patterns EDOU patients, (2) physicians' adherence to the IDSA guidelines, and (3) factors that influence physician's prescribing practices. METHODS: This prospective cohort enrolled adult patients discharged from an EDOU at an academic medical center after treatment for a skin or soft tissue infection. Information was collected from chart review and patient interview pertaining to the patient's sociodemographic characteristics, presenting illness, and antibiotic treatment regimens. Treatment regimens were compared with national guidelines. RESULTS: The study included 193 patients of which only 43% were treated according to IDSA guidelines, 42% were overtreated, and 15% were undertreated. Women were more likely to be undertreated (relative risk, 1.58; 95% confidence interval, 1.21-2.06), whereas patients 50 years and older were at risk for overtreatment (relative risk, 1.44; 95% confidence interval, 1.03-2.02). Women also received shorter courses of antibiotic therapy with an average of 9.6 days of treatment compared with 10.6 days for men. CONCLUSIONS: Physician antibiotic prescribing practices demonstrated poor adherence to IDSA guidelines and were influenced by the patient's age and sex. Standardized antibiotic protocols for treatment of skin and soft tissue infections to IDSA guidelines in the EDOU would minimize physician bias. PMID- 26381682 TI - Can physician and patient gestalt lead to a shared decision to reduce unnecessary radiography in extremity trauma? PMID- 26381683 TI - Weekend hospitalization and inhospital mortality: a gender effect? PMID- 26381684 TI - Socioeconomic Disparities and Air Pollution Exposure: a Global Review. AB - The existing reviews and meta-analyses addressing unequal exposure of environmental hazards on certain populations have focused on several environmental pollutants or on the siting of hazardous facilities. This review updates and contributes to the environmental inequality literature by focusing on ambient criteria air pollutants (including NOx), by evaluating studies related to inequality by socioeconomic status (as opposed to race/ethnicity) and by providing a more global perspective. Overall, most North American studies have shown that areas where low-socioeconomic-status (SES) communities dwell experience higher concentrations of criteria air pollutants, while European research has been mixed. Research from Asia, Africa, and other parts of the world has shown a general trend similar to that of North America, but research in these parts of the world is limited. PMID- 26381685 TI - Morphometry and variations of the human suprascapular notch. AB - AIM: The present study proposes a simple method to study variations in shape and dimensions of suprascapular notch, to classify different types and subtypes of notch and to measure the thickness of superior transverse scapular bar (ossified superior transverse ligament of scapula). MATERIAL AND METHODS: Seven hundred and twenty-eight dried scapulae were observed, examined and studied in detail. Scapulae with suprascapular notch, with suprascapular foramen having varying degree of ossification in the form of transverse scapular bar were included in the present study. Measurements of suprascapular notch and superior transverse scapular bar were taken with the help of digital vernier calliper and recorded in millimetres. The superior transverse diameter, inferior transverse diameter, depth, maximum thickness of suprascapular notch and thickness at lateral and medial end of transverse scapular bar, mean thickness of superior transverse scapular bar were recorded. The data was analyzed statistically. OBSERVATIONS AND RESULTS: We observed five types of notch in scapulae, type I: without a discrete notch (ill defined), 25 (3.43%); type II: a "V" shaped notch, 192 (26.37%); type III: "U" shaped notch, 383 (52.60%); type IV: inverted "V" shaped notch, 28 (3.84%); type V with absent suprascapular notch: 6 (0.82%). Type II and type III were again subclassified into subtypes (a, b, c and d) on the basis of depth of notch. Scapulae with superior transverse scapular bar (n=94, 12.91%) were classified according to variation in mean thickness of transverse scapular bar (MTSB). CONCLUSION: This study will help clinicians to correlate suprascapular nerve entrapment with a specific type of suprascapular notch and notch with ossified transverse scapular ligament. PMID- 26381686 TI - Conformational flexibility of viral RNA switches studied by FRET. AB - The function of RNA switches involved in the regulation of transcription and translation relies on their ability to adopt different, structurally well-defined states. A new class of ligand-responsive RNA switches, which we recently discovered in positive strand RNA viruses, are distinct from conventional riboswitches. The viral switches undergo large conformational changes in response to ligand binding while retaining the same secondary structure in their free and ligand-bound forms. Here, we describe FRET experiments to study folding and ligand binding of the viral RNA switches. In addition to reviewing previous approaches involving RNA model constructs which were directly conjugated with fluorescent dyes, we outline the design and application of new modular constructs for FRET experiments, in which dye labeling is achieved by hybridization of a core RNA switch module with universal DNA fluorescent probes. As an example, folding and ligand binding of the RNA switch from the internal ribosome entry site of hepatitis C virus is studied comparatively with conventional and modular FRET constructs. PMID- 26381687 TI - The effect of vitamin E on lung pathology in sulfur mustard-exposed guinea pigs. AB - Pulmonary complications of exposure to sulfur mustard (SM) gas range from no effect or mild symptoms to severe bronchial stenosis. In the present study, the protective effect of vitamin E on the lung inflammation of SM-exposed guinea pigs was examined. Guinea pigs (n = 5 for each group) were exposed to ethanol (control group), 40 mg/m3 inhaled SM (SME group), SME treated with vitamin E (SME + E), SME treated with dexamethasone (SME + D), and SME treated with both treatments (SME + E + D). Pathological evaluation of the lung was done 14 days postexposure. The epithelial desquamation of trachea and other pathologic changes in the lung of the SME group were significantly higher than those in the control group. Furthermore, the pathological changes of trachea and lung in the SME + E and SME + E + D groups were significantly improved compared with those of SME group. In addition, the pathological changes of trachea and lung of SME + E and SME + E + D animals were significantly less than those of SME + D group. PMID- 26381688 TI - Eugenol and carvone as relaxants of arsenic and mercury hypercontracted rat trachea. AB - Exposure to arsenic and mercury is known to cause respiratory problems in both humans and animals. In this study, we elicit and compare maximum contraction caused by As(III) and Hg(II) when the pollutants are fully equilibrated with contractile machinery in resting mode. Hypercontraction of 27% and 69% was obtained following exposure of tracheal rings to 25 uM As(III) and 6 nM Hg(II) for 40 min, respectively. Co-incubation of tracheal rings with pollutants and verapamil, sodium nitroprusside or apocynin indicates that major contributors to As(III) and Hg(II) caused hypercontraction are reactive oxygen species (ROS) elevation and nitric oxide (NO) depletion. Changes in calcium influx have minor contribution in As(III) and Hg(II) caused increased contraction of tracheal tissues. Eugenol and carvone caused relaxation of 38% and 45% in pollutant unexposed rings, 56% and 49% in As(III)-exposed tracheal rings, and 54% and 47% in Hg(II)-exposed tracheal rings. Pathway delineation studies indicate that the major effect of eugenol originates from quenching of ROS whereas that of carvone originates from the blockage of extracellular calcium influx. Both molecules also show a minor stimulatory effect on NO generation. In line with their suggested mode of relaxation, eugenol is found to better ameliorate both As(III)- and Hg(II)-caused hypercontraction. Carvone, though a better relaxant than eugenol, comes out as poor ameliorator of both As(III)- and Hg(II)-caused hypercontraction, as the pathway on which it acts is not elevated following exposure to these pollutants. PMID- 26381689 TI - Modulatory role of GSTM1 null genotype on the frequency of micronuclei in pesticide-exposed agricultural workers. AB - In this study, we aimed to investigate the extent of genotoxic risk and the association between null GSTM1/GSTT1 and GSTP1 Ile105Val variants and cellular DNA damage, as measured by micronucleus (MN) assay in a group of agricultural workers from Denizli, Turkey. Peripheral blood samples were collected from 116 subjects, including 58 workers who were occupationally exposed to pesticides and 58 healthy unexposed controls. The MN frequencies of each individual were assessed by cytokinesis-blocked micronuclei assays on lymphocytes. Genotypes for different GST variants were determined using polymerase chain reaction-based methods. A significant 3.4-fold increase in MN frequency was observed in workers compared with the controls (p < 0.001). Among the GST genotypes, only the GSTM1 null genotype was found to be significantly associated with an increased MN frequency in workers (p = 0.01). Individuals with a concomitant null GSTM1/GSTT1 genotype demonstrated a significant (p = 0.01) increase in MN frequency compared with those with functional isozymes in the exposed worker group. The association of the GSTM1 null genotype with higher MN frequency suggests that it may be a modifier of genotoxic risk in individuals exposed to pesticides and may thus be a candidate susceptibility biomarker for human biomonitoring studies. PMID- 26381690 TI - Telomere length, telomerase expression, and oxidative stress in lead smelters. AB - The negative health effects caused by lead (Pb) exposure are widely recognized; however, the molecular mechanisms remain unknown. The aim of this study was to assess the effect of occupational Pb exposure on telomere length and to investigate the potential mechanisms leading to telomere shortening. A cohort of 334 male Pb smelters (exposed group) and 60 age-adjusted males unexposed to Pb (control group) were examined. Assessments of relative telomere length (rTL) and telomerase reverse transcriptase (TERT) gene expression were performed using quantitative real-time polymerase chain reactions. Assessments of whole blood Pb (B-Pb) and whole blood cadmium (B-Cd) concentrations and serum selenium concentration (S-Se) were performed using graphite furnace atomic absorption spectrometry. We analyzed total oxidation status (TOS), lipid hydroperoxides (LHPs), malonylodialdehyde levels in serum (MDA) and in erythrocyte hemolysates (MDA-hgb), and 8-hydroxy-deoxy-guanosine (8-OHdG). The Pb-exposed group had higher B-Pb values and shorter rTL than the control group. The arithmetic mean values calculated for B-Pb were 33 ug/dL versus 2.2 ug/dL (p < 0.0001), and the rTL values were 0.928 and 1.126 relative units (p = 0.001), respectively, for the Pb-exposed and control groups. The rTL was found to gradually shorten in response to the increasing levels of Pb exposure. The Pb-exposed group also demonstrated a higher level of oxidative stress than the control group, which was indicated by increased TOS and MDA-hgb values. rTL was negatively associated with parameters that indicated increased oxidative stress, including TOS (Spearman's rank coefficient (rS) = -0.16; p < 0.01) and MDA-hgb (rS = -0.17; p < 0.001). No correlations were found between rTL and B-Cd and S-Se or smoking and MDA and LHP levels. Univariate analysis indicated that B-Pb was associated with decreased rTL (beta =-0.0041; p = 0.0063) and that the association between B-Pb and rTL remained significant, even when adjusting for age (beta = -0.0041; p = 0.0065) and in multivariable-adjusted model (beta = -0.0042; p = 0.0063). In conclusion, occupational Pb exposure resulted in decreased rTL and may represent a mechanism that contributes to Pb-related diseases. PMID- 26381691 TI - Roles of oxidative stress, apoptosis, and heme oxygenase-1 in ethylbenzene induced renal toxicity in NRK-52E cells. AB - Ethylbenzene is an important industrial chemical, but its potential toxicity is a recent concern. Our previous study investigated the renal toxicity of ethylbenzene in vivo Rat renal epithelial cells (NRK-52E cells) were incubated with 0, 30, 60, and 90 umol/L of ethylbenzene for 24 h in vitro to investigate ethylbenzene-induced oxidative stress, apoptosis, and the expression of heme oxygenase 1 (HO-1) and nuclear factor (erythroid 2)-related factor 2 (Nrf2). The cell survival rate in the ethylbenzene-treated groups was significantly lower than the control group. Ethylbenzene significantly increased intracellular reactive oxygen species and apoptosis. Malondialdehyde levels were significantly elevated compared with the control group, while glutathione levels and glutathione peroxidase activities were decreased in ethylbenzene-treated groups. The activities of catalase and superoxide dismutase were also markedly reduced. A significant dose-dependent increase in HO-1 and Nrf2 messenger RNA expression levels was observed in ethylbenzene-treated groups compared with the control group. Similarly, ethylbenzene treatment enhanced protein expression of HO-1 and Nrf2 in a dose-dependent manner. Our results indicated that ethylbenzene induced oxidative stress, apoptosis, and upregulation of HO-1 and Nrf2 in NRK-52E cells, which contributes to ethylbenzene-induced renal toxicity. PMID- 26381692 TI - The relationship between temperament and character and psychotic-like experiences in healthy children and adolescents. AB - BACKGROUND: Prior work by our group identified personality profiles associated with psychotic-like experiences (PLE's) in healthy adults that were strikingly similar to those found in schizophrenia patients, with the exception of two key differences. Specifically, higher levels of PLE's were linked to higher persistence and cooperativeness, suggesting that these characteristics might represent personality-based resilience factors. Notably, age and personality were significantly correlated in these data, raising questions about whether healthy children and adolescents would show similar results. To date, no study has examined personality profiles associated with both positive and negative PLE's in healthy children and adolescents using Cloninger's Temperament and Character Inventory (TCI). Thus, this study examined the relationship between TCI dimensions and PLE's in healthy children and adolescents. METHOD: The TCI and the Community Assessment of Psychic Experiences (CAPE) were administered to 123 healthy children and adolescents aged 8-18. Multiple regression models were used to examine personality dimensions associated with overall severity of PLE's as well as severity of positive and negative PLE's separately. RESULTS: Positive, negative, and overall PLE severity were all associated with a personality pattern of higher harm avoidance and lower self-directedness. Negative PLE severity was also associated with lower persistence. CONCLUSIONS: Personality correlates of PLE's in healthy children and adolescents were largely consistent with our past work on PLE's in healthy adults. However, our previously identified resilience factors were notably absent in this sample. These findings may suggest that these personality characteristics have not yet crystallized or emerged to aid in coping with PLE's. PMID- 26381694 TI - Preparation of Porous Three-Dimensional Quaternary Thioantimonates(III) ACuSb2 S4 (A = Rb, Cs) through a Surfactant-Thermal Method. AB - Two novel porous three-dimensional (3D) quaternary thioantimonates(III) ACuSb2S4 (A = Rb, Cs) were successfully synthesized by employing the neutral surfactant PEG-400 (PEG = polyethyleneglycol) as reaction media, these are significantly different from the known quaternary A-Cu-Sb-S thioantimonates(III) with two dimensional (2D) crystal structures. This is the first time that crystalline quaternary chalcogenides have been prepared in surfactant media. Both experimental and theoretical studies confirm they are semiconductors with narrow band gaps. Our results demonstrated that the surfactant-thermal strategy could offer a new opportunity to explore novel chalcogenides with diverse crystal structures and interesting physicochemical properties. PMID- 26381693 TI - Manganese in teeth and neurodevelopment in young Mexican-American children. AB - INTRODUCTION: Manganese (Mn) is an essential nutrient but higher exposure has been associated with poorer neurodevelopment in children. METHODS: We measured Mn levels in prenatal (Mnpre) (n=197) and postnatal (Mnpost) dentin (n=193) from children's shed teeth using laser ablation inductively coupled plasma mass spectroscopy and examined the relationship with children's scores on the Mental Development Index (MDI) and Psychomotor Development Index (PDI) on the Bayley Scales of Infant Development at 6, 12, and 24-months. We explored non-linear associations and interactions by sex, blood lead concentrations and maternal iron status during pregnancy. RESULTS: A two-fold increase of Mnpost levels in dentin was associated with small decreases in MDI at 6-months and 12-months of age. We also observed a non-linear relationship between Mnpost levels and PDI at 6 months. We found effect modification by sex for Mnpost levels and neurodevelopment at 6-months with stronger effects among girls for both MDI (-1.5 points; 95% Confidence Interval (CI): -2.4, -0.6) and PDI (-1.8 points; 95% CI: 3.3, -0.3). Girls whose mothers had lower hemoglobin levels experienced larger decreases in MDI and PDI associated with Mnpre levels than girls whose mothers had higher hemoglobin levels (pinteraction=0.007 and 0.09, respectively). We did not observe interactions with blood lead concentrations or any relationships with neurodevelopment at 24-months. CONCLUSIONS: Using Mn measurements in tooth dentin, a novel biomarker that provides prenatal and early postnatal levels, we observed negative transient associations between postnatal Mn levels and early neurodevelopment with effect modification by sex and interactions with prenatal hemoglobin. PMID- 26381695 TI - Sandwich-like mesoporous silica flakes for anticancer drug transport-Synthesis, characterization and kinetics release study. AB - In this paper, we present the technology of synthesis, characterization and release kinetics of anticancer drug molecules from sandwich-like mesoporous silica nanoflakes. Mesoporous silica nanoflakes are a very attractive material due to their versatility, low cytotoxicity, large surface area, high pore volume and unique feature of containing parallel pores openon both sides. Nanosilica flakes were prepared through the formation of a mesoporous silica layer on a graphene oxide surface. After graphene oxide removal, the silica nanostructures were filled by an anticancer drug-methotrexate. Release kinetics studies were performed in different temperatures, imitating the conditions in living organisms. Release data was analyzed using the zero-order model, first-order model, Higuchi model and Korsmeyer-Peppas model. The optical properties of samples, and the kinetics of drug release from the nanostructure, were examined by UV-vis spectrophotometer. Data obtained from long term studies showed that the system can serve as an anticancer drug carrier system, since a significant amount of methotrexate was loaded to the material and released. The mechanism of MTX release from mesoporous silica nanoflakes appeared to be a parallel processes of diffusion through water-filled mesopores and degradation of the mSiO2 matrix. Physical and chemical characterization was undertaken by transmission electron microscopy (TEM) and X-ray dispersion spectroscopy (EDX). The specific surface area of the samples was measured through the adsorption of N2 isotherm, interpreted with the Brunauer-Emmett-Teller model (BET). TGA and UV-vis analyses were conducted in order to estimate the amount of the released drug. PMID- 26381696 TI - Crack-free polydimethylsiloxane-bioactive glass-poly(ethylene glycol) hybrid monoliths with controlled biomineralization activity and mechanical property for bone tissue regeneration. AB - Crack-free organic-inorganic hybrid monoliths with controlled biomineralization activity and mechanical property have an important role for highly efficient bone tissue regeneration. Here, biomimetic and crack-free polydimethylsiloxane (PDMS) modified bioactive glass (BG)-poly(ethylene glycol) (PEG) (PDMS-BG-PEG) hybrids monoliths were prepared by a facile sol-gel technique. Results indicate that under the assist of co-solvents, BG sol and PDMS and PEG could be hybridized at a molecular level, and effects of the PEG molecular weight on the structure, biomineralization activity, and mechanical property of the as-prepared hybrid monoliths were also investigated in detail. It is found that an addition of low molecular weight PEG can significantly prevent the formation of cracks and speed up the gelation of the hybrid monoliths, and the surface microstructure of the hybrid monoliths can be changed from the porous to the smooth as the PEG molecular weight increases. Additionally, the hybrid monoliths with low molecular weight PEG show the high formation of the biological apatite layer, while the hybrids with high molecular weight PEG exhibit negligible biomineralization ability in simulated body fluid (SBF). Furthermore, the PDMS-BG-PEG 600 hybrid monolith has significantly high compressive strength (32 +/- 3 MPa) and modulus (153 +/- 11 MPa), as well as good cell biocompatibility by supporting osteoblast (MC3T3-E1) attachment and proliferation. These results indicate that the as prepared PDMS-BG-PEG hybrid monoliths may have promising applications for bone tissue regeneration. PMID- 26381697 TI - N-doped carbon dots derived from bovine serum albumin and formic acid with one- and two-photon fluorescence for live cell nuclear imaging. AB - Carbon dots with both one- and two-photon fluorescence have drawn great attention for biomedical imaging. Herein, nitrogen-doped carbon dots were facilely developed by one-pot hydrothermal method using bovine serum albumin and formic acid as carbon sources. They are highly water-soluble with strong fluorescence when excited with ultraviolet or near infrared light. The carbon dots have a diameter of ~8.32 nm and can emit strong two-photon induced fluorescence upon excitation at 750 nm with a femtosecond laser. X-ray photoelectron spectrometer analysis revealed that the carbon dots contained three components, C, N and O, corresponding to the peak at 285, 398 and 532 eV, respectively. The Fourier transform infrared spectroscopy analysis revealed that there are carboxyl and carboxylic groups on the surface, which allowed further linking of functional molecules. pH stability study demonstrated that the carbon dots are able to be used in a wide range of pH values. The fluorescence mechanism is also discussed in this study. Importantly, these carbon dots are biocompatible and highly photostable, which can be directly applied for both one- and two-photon living cell imaging. After proper surface functionalization with TAT peptide, they can be used as fluorescent probes for live cell nuclear-targeted imaging. PMID- 26381698 TI - Development of 4-sulfated N-acetyl galactosamine anchored chitosan nanoparticles: A dual strategy for effective management of Leishmaniasis. AB - The present investigation reports the modification of chitosan nanoparticles with a ligand 4-sulfated N-acetyl galactosamine (4-SO4GalNAc) for efficient chemotherapy in leishmaniasis (SCNPs) by using dual strategy of targeting. These (SCNPs) were loaded with amphotericin B (AmB) for specific delivery to infected macrophages. Developed AmB loaded SCNPs (AmB-SCNPs) had mean particle size of 333 +/- 7 nm, and showed negative zeta potential (-13.9 +/- 0.016 mV). Flow cytometric analysis revealed enhanced uptake of AmB-SCNPs in J774A.1, when compared to AmB loaded unmodified chitosan NPs (AmB-CNPs). AmB-SCNPs provide significantly higher localization of AmB in liver and spleen as compared to AmB CNPs after i.v. administration. The study stipulates that 4-SO4GalNAc assures of targeting, resident macrophages. Highly significant anti-leishmanial activity (P<0.05 compared with AmB-CNPs) was observed with AmB-SCNPs, causing 75.30 +/- 3.76% inhibition of splenic parasitic burdens. AmB-CNPs and plain AmB caused only 63.89 +/- 3.44% and 47.56 +/- 2.37% parasite inhibition, respectively, in Leishmania-infected hamsters (P<0.01 for AmB-SCNPs versus plain AmB and AmB-CNPs versus plain AmB). PMID- 26381699 TI - Dynamic and social behaviors of human pluripotent stem cells. AB - Human pluripotent stem cells (hPSCs) can self-renew or differentiate to diverse cell types, thus providing a platform for basic and clinical applications. However, pluripotent stem cell populations are heterogeneous and functional properties at the single cell level are poorly documented leading to inefficiencies in differentiation and concerns regarding reproducibility and safety. Here, we use non-invasive time-lapse imaging to continuously examine hPSC maintenance and differentiation and to predict cell viability and fate. We document dynamic behaviors and social interactions that prospectively distinguish hPSC survival, self-renewal, and differentiation. Results highlight the molecular role of E-cadherin not only for cell-cell contact but also for clonal propagation of hPSCs. Results indicate that use of continuous time-lapse imaging can distinguish cellular heterogeneity with respect to pluripotency as well as a subset of karyotypic abnormalities whose dynamic properties were monitored. PMID- 26381700 TI - Terahertz field control of in-plane orbital order in La(0.5)Sr(1.5)MnO4. AB - In-plane anisotropic ground states are ubiquitous in correlated solids such as pnictides, cuprates and manganites. They can arise from doping Mott insulators and compete with phases such as superconductivity; however, their origins are debated. Strong coupling between lattice, charge, orbital and spin degrees of freedom results in simultaneous ordering of multiple parameters, masking the mechanism that drives the transition. Here we demonstrate that the orbital domains in a manganite can be oriented by the polarization of a pulsed THz light field. Through the application of a Hubbard model, we show that domain control can be achieved by enhancing the local Coulomb interactions, which drive domain reorientation. Our results highlight the key role played by the Coulomb interaction in the control and manipulation of orbital order in the manganites and demonstrate a new way to use THz to understand and manipulate anisotropic phases in a potentially broad range of correlated materials. PMID- 26381701 TI - Trajectories of postsurgical pain in children: risk factors and impact of late pain recovery on long-term health outcomes after major surgery. AB - Over 1 million children undergo inpatient surgery annually in the United States. Emerging research indicates that many children have longer-term problems with pain. However, limited data exist on the course of pain over time and the impact of pain recovery on long-term health outcomes. We sought to prospectively characterize children's postsurgical pain trajectories using repeated assessments over 12 months. In addition, we identified presurgical child and parent psychological risk factors associated with persistent pain and examined relationships between pain trajectories and long-term health outcomes. Sixty children aged 10 to 18 years undergoing major surgery and their parent/guardian were enrolled. Participants completed assessments at 5 time points: presurgery, inhospital, 2 weeks, 4 months, and 1 year postsurgery. Child and parent pain catastrophizing was assessed during the week before surgery. Children completed daily monitoring with an electronic pain diary and reported on pain characteristics, health-related quality of life, and activity limitations. Group based longitudinal modeling revealed 2 distinct trajectories of postsurgical pain: early recovery (n = 49, 82%) and late recovery (n = 11, 18%). In a logistic regression model controlling for age and sex, parental pain catastrophizing before surgery significantly predicted membership in the late recovery group (odds ratio = 1.11, P = 0.03), whereas child catastrophizing and baseline pain did not (Ps < 0.05). In a multivariate regression controlling for age and sex, late pain recovery was significantly associated with poorer health-related quality of life (beta = -10.7, P = 0.02) and greater activity limitations (beta = 3.6, P = 0.04) at 1 year. Our findings suggest that preoperative interventions that modify parent behaviors and cognitions might be beneficial in this population. PMID- 26381703 TI - Corrigendum: Toll-like receptor-2 deficiency induces schizophrenia-like behaviors in mice. PMID- 26381702 TI - Replication of Leaf Surface Structures for Light Harvesting. AB - As one of the most important hosts of natural light harvesting, foliage normally has complicated surface structures to capture solar radiances. Bio-mimicking leaf surface structures can provide novel designs of covers in photovoltaic systems. In this article, we reported on replicating leaf surface structures on poly (methyl methacrylate) polymers to prompt harvesting efficiencies. Prepared via a double transfer process, the polymers were found to have high optical transparencies and transmission hazes, with both values exceeding 80% in some species. Benefiting from optical properties and wrinkled surfaces, the biomimetic polymers brought up to 17% gains to photovoltaic efficiencies. Through Monte Carlo simulations of light transport, ultrahigh haze values and low reflections were attributed to lightwave guidance schemes lead by the nano- and micro morphologies which are inherited from master leaves. Thus, leaf surface bio mimicking can be considered as a strategic direction to design covers of light harvesting systems. PMID- 26381704 TI - On the non-classical contribution in lone-pair-pi interaction: IQA perspective. AB - In the present work the nature of lone-pair-pi interactions between water molecules and a number of pi-rings with different substituents/hetero-atoms in the light of quantum chemical topology approaches is studied. The Quantum Theory of Atoms in Molecules (QTAIM) and Interacting Quantum Atoms (IQA) were employed for distinguishing the role of heteroatoms and electron withdrawing substituents in the complex formation between water and pi-rings. Our IQA study identified three classes of water-pi complexes on the basis of the relative role of electrostatics (classical) and exchange-correlation (non-classical) factors in the interaction energy between the oxygen of water (the lone-pair donor) and the sp(2) atoms of the pi-ring, i.e. the primary lp-pi interaction. Considering both the primary and secondary (the rest of interatomic interactions except Owater-pi ring atoms) interactions demonstrates that the exchange-correlation is the dominant contributor to the binding energy. This proves a non-negligible contribution of non-classical factors in the stabilization of the lone-pair-pi complexes. However, in spite of a relatively large contribution of the exchange correlation, this part of the interaction energy is virtually counterbalanced by the deformation energy, i.e. the increase in atomic kinetic energy upon complexation. This finding clarifies why water-pi interactions can be modelled by simple electrostatics without the need to invoke quantum effects. PMID- 26381706 TI - Antibodies: friend or foe? PMID- 26381707 TI - Using nanoimprint lithography to improve the light extraction efficiency and color rendering of dichromatic white light-emitting diodes. AB - Despite the efficiency of gallium nitride (GaN)-based blue light-emitting diodes (LEDs), the light extraction arising from the packaging of the phosphor remains an important issue when enhancing the performance of dichromatic white LEDs. In this study, we employed a simple, inexpensive nanoimprinting process to increase both the light extraction efficiency and color rendering of dichromatic white LEDs. We employed the rigorous coupled wave approach (RCWA) to optimize the light extraction efficiency of yellow and blue light. We found that the presence of the light extracting structures could also improve the color rendering of the dichromatic white LEDs, due to the different light extraction efficiencies of the textured structures at different wavelengths. After fabricating inverted pyramid structures on the surface of the encapsulation layer, the intensity of the blue light at 455 nm increased by 20%. When we further considered the color rendering and correlated color temperature (CCT), the enhancement of blue light was 15% and that of yellow light was 4%. Meanwhile, the light extraction of the intensity dip near 490 nm was enhanced significantly (by 25%), resulting in an increased dip intensity of light at 490 nm relative to the intensities of the blue and yellow light. Accordingly, the color rendering index (CRI) of this dichromatic white LED increased from 69 to 73. Because it improved both the light extraction efficiency and color rendering of dichromatic white LEDs, this simple method should be very helpful for enhancing their applications in solid state illumination. PMID- 26381705 TI - Bilirubin prevents acute DSS-induced colitis by inhibiting leukocyte infiltration and suppressing upregulation of inducible nitric oxide synthase. AB - Bilirubin is thought to exert anti-inflammatory effects by inhibiting vascular cell adhesion molecule-1 (VCAM-1)-dependent leukocyte migration and by suppressing the expression of inducible nitric oxide synthase (iNOS). As VCAM-1 and iNOS are important mediators of tissue injury in the dextran sodium sulfate (DSS) murine model of inflammatory colitis, we examined whether bilirubin prevents colonic injury in DSS-treated mice. Male C57BL/6 mice were administered 2.5% DSS in the drinking water for 7 days, while simultaneously receiving intraperitoneal injections of bilirubin (30 mg/kg) or potassium phosphate vehicle. Disease activity was monitored, peripheral blood counts and serum nitrate levels were determined, and intestinal specimens were analyzed for histological injury, leukocyte infiltration, and iNOS expression. The effect of bilirubin on IL-5 production by HSB-2 cells and on Jurkat cell transendothelial migration also was determined. DSS-treated mice that simultaneously received bilirubin lost less body weight, had lower serum nitrate levels, and exhibited reduced disease severity than vehicle-treated animals. Concordantly, histopathological analyses revealed that bilirubin-treated mice manifested significantly less colonic injury, including reduced infiltration of eosinophils, lymphocytes, and monocytes, and diminished iNOS expression. Bilirubin administration also was associated with decreased eosinophil and monocyte infiltration into the small intestine, with a corresponding increase in peripheral blood eosinophilia. Bilirubin prevented Jurkat migration but did not alter IL-5 production. In conclusion, bilirubin prevents DSS-induced colitis by inhibiting the migration of leukocytes across the vascular endothelium and by suppressing iNOS expression. PMID- 26381708 TI - Fabrication and Operation of a Nano-Optical Conveyor Belt. AB - The technique of using focused laser beams to trap and exert forces on small particles has enabled many pivotal discoveries in the nanoscale biological and physical sciences over the past few decades. The progress made in this field invites further study of even smaller systems and at a larger scale, with tools that could be distributed more easily and made more widely available. Unfortunately, the fundamental laws of diffraction limit the minimum size of the focal spot of a laser beam, which makes particles smaller than a half-wavelength in diameter hard to trap and generally prevents an operator from discriminating between particles which are closer together than one half-wavelength. This precludes the optical manipulation of many closely-spaced nanoparticles and limits the resolution of optical-mechanical systems. Furthermore, manipulation using focused beams requires beam-forming or steering optics, which can be very bulky and expensive. To address these limitations in the system scalability of conventional optical trapping our lab has devised an alternative technique which utilizes near-field optics to move particles across a chip. Instead of focusing laser beams in the far-field, the optical near field of plasmonic resonators produces the necessary local optical intensity enhancement to overcome the restrictions of diffraction and manipulate particles at higher resolution. Closely-spaced resonators produce strong optical traps which can be addressed to mediate the hand-off of particles from one to the next in a conveyor-belt-like fashion. Here, we describe how to design and produce a conveyor belt using a gold surface patterned with plasmonic C-shaped resonators and how to operate it with polarized laser light to achieve super-resolution nanoparticle manipulation and transport. The nano-optical conveyor belt chip can be produced using lithography techniques and easily packaged and distributed. PMID- 26381709 TI - Synthesis and Properties of Ethene-Bridged Terthiophenes. AB - A method for the facile synthesis of ethene-bridged terthiophenes (EBTTs) in two steps has been developed. The first step is a double Sonogashira coupling between 3',4'-dibromo-2,2':5',2"-terthiophene and terminal alkynes to give dialkynylated terthiophenes, and the second step is a cyclization reaction to afford EBTTs. The fundamental physical properties of EBTTs were also studied. PMID- 26381710 TI - Allocrite Sensing and Binding by the Breast Cancer Resistance Protein (ABCG2) and P-Glycoprotein (ABCB1). AB - The ATP binding cassette (ABC) transporters ABCG2 and ABCB1 perform ATP hydrolysis-dependent efflux of structurally highly diverse compounds, collectively called allocrites. Whereas much is known about allocrite-ABCB1 interactions, the chemical nature and strength of ABCG2-allocrite interactions have not yet been assessed. We quantified and characterized interactions of allocrite with ABCG2 and ABCB1 using a set of 39 diverse compounds. We also investigated potential allocrite binding sites based on available transporter structures and structural models. We demonstrate that ABCG2 binds its allocrites from the lipid membrane, despite their hydrophilicity. Hence, binding of allocrite to both transporters is a two-step process, starting with a lipid-water partitioning step, driven mainly by hydrophobic interactions, followed by a transporter binding step in the lipid membrane. We show that binding of allocrite to both transporters increases with the number of hydrogen bond acceptors in allocrites. Scrutinizing the transporter translocation pathways revealed ample hydrogen bond donors for allocrite binding. Importantly, the hydrogen bond donor strength is, on average, higher in ABCG2 than in ABCB1, which explains the higher measured affinity of allocrite for ABCG2. pi-pi stacking and pi-cation interactions play additional roles in binding of allocrite to ABCG2 and ABCB1. With this analysis, we demonstrate that these membrane-mediated weak electrostatic interactions between transporters and allocrites allow for transporter promiscuity toward allocrites. The different sensitivities of the transporters to allocrites' charge and amphiphilicity provide transporter specificity. In addition, we show that the different hydrogen bond donor strengths in the two transporters allow for affinity tuning. PMID- 26381711 TI - Several Ryanodine Receptor Type 1 Gene Mutations of p.Arg2508 Are Potential Sources of Malignant Hyperthermia. AB - BACKGROUND: Malignant hyperthermia (MH) is a pharmacogenetic disorder that occurs in predisposed individuals after exposure to volatile anesthetics or depolarizing muscle relaxants. Genetic mutations of ryanodine receptor 1 (RYR1), which are considered to cause MH, are found mainly in 3 regions called "hotspots." There are sometimes multiple mutations at the same site of RYR1. Although p.Arg2508 of RYR1 is located outside hotspots, several mutations or variants (including the known MH causative mutation p.Arg2508Cys) have been identified in this region. We hypothesized that any mutations or variants in RYR1 p.Arg2508 cause important changes in pathological conditions related to MH. In this study, we analyzed the functions of 4 different RYR1 variants containing mutations at p.Arg2508. METHODS: We prepared and analyzed the functions of 4 mutated RYR1 genes: p.Arg2508His and p.Arg2508Gly are MH-related variants, whereas p.Arg2508Ser and p.Arg2508Lys have not been previously reported. Because the biochemical characteristics of lysine are similar to arginine, we assumed that p.Arg2508Lys RYR1 would have characteristics most similar to those of the wild-type RYR1. We introduced these 4 mutated RYR1 genes, p.Arg2508His, p.Arg2508Gly, p.Arg2508Ser, and p.Arg2508Lys into rabbit RYR1 cDNA and transfected the resultant clones into human embryonic kidney 293 cells. Using the ratiometric dye Fura-2 AM, we used the 340/380 nm ratio to analyze alterations in calcium homeostasis after stimulation with caffeine and 4-chloro-m-cresol (4CmC). We calculated the half maximal activation concentrations (EC50) of cells transfected with each mutant and compared the EC50 value of cells expressing each mutant with that of cells expressing wild-type RYR1. Statistical significance between EC50 values were calculated using an unpaired 2-tailed t test. We used 300 different cells, by 30 cells in each of the wild type or mutant. RESULTS: Cells transfected with each of the 4 mutants, p.Arg2508His, p.Arg2508Gly, p.Arg2508Ser, or p.Arg2508Lys, were more sensitive to caffeine and 4CmC than cells transfected with the wild type (all 4 P <= 0.0004). Mean +/- SD of EC50 values for caffeine of wild type, p.Arg2508His, p.Arg2508Gly, p.Arg2508Ser, and p.Arg2508Lys were 2.53 +/- 0.89, 1.72 +/- 0.72, 1.73 +/- 0.79, 1.69 +/- 0.80, and 1.61 +/- 0.74 mM, respectively, and those for 4CmC were 125.92 +/- 38.11, 70.42 +/- 27.09, 79.30 +/- 39.04, 73.03 +/- 19.20, and 72.81 +/- 28.44 mM, respectively. CONCLUSIONS: Any of these 4 mutations in RYR1 p.Arg2508 may cause important changes related to MH. Studying the effects of changes in amino acids at 2508 in RYR1 on the movement of this large protein may lead to a better understanding of the pathology of MH events. PMID- 26381712 TI - Role of Water in the Puzzling Mechanism of the Final Aromatization Step Promoted by the Human Aromatase Enzyme. Insights from QM/MM MD Simulations. AB - The enzyme human aromatase (HA) catalyzes the conversion of androgens to estrogens via two hydroxylation reactions and a final unique aromatization step. Despite the great interest of HA as a drug target against breast cancer detailed structural and spectroscopic information on this enzyme became available only in the past few years. As such, the enigmatic mechanism of the final aromatization step is still a matter of debate. Here, we investigated the final step of the HA enzymatic cycle via hybrid quantum-classical (QM/MM) metadynamics and blue-moon ensemble simulations. Our results show that the rate-determining step of the aromatization process is the nucleophilic attack of the distal oxygen of a peroxo ferric species on the formyl carbon of the enol-19-oxo-androstenedione, which occurs with a free energy barrier (DeltaF(#)) of ~ 16.7 +/- 1.9 kcal/mol, in good agreement with experimental data. This reaction is followed by a water mediated 1beta-hydrogen abstraction (DeltaF(#) = 7.9 +/- 0.8 kcal/mol) and by the formation of a hydroxo-ferric moiety. This latter may be finally protonated by a hydrogen delivery channel involving Asp309 and Thr310, both residues pointed out as crucial for HA activity. In the absence of the catalytic water in the active site the substrate does not assume a position suitable to undergo the nucleophilic attack. Our data not only reveal a novel possible mechanism for the aromatization process consistent with some of the spectroscopic and kinetic data available in the literature, complementing current knowledge on the mechanism of this enzyme, but also point out a remarkable influence of the level of theory used on the calculated free energy barriers. The structural information obtained in this study may be used for the rational structure-based drug design of HA inhibitors to be employed in breast cancer therapy. PMID- 26381713 TI - Characteristics of vertigo and the affected vestibular nerve systems in idiopathic bilateral vestibulopathy. AB - CONCLUSION: Vertigo attacks in IBV patients involving both the superior and inferior vestibular nerve systems were significantly more severe than vertigo attacks in patients with selective involvement of the inferior vestibular nerve system alone. OBJECTIVE: To investigate the relationship between the frequency and duration of vertigo and the affected vestibular nerve system in idiopathic bilateral vestibulopathy (IBV). METHODS: This study categorized 44 IBV patients into the following three sub-groups according to the affected vestibular nerve system: superior, inferior, and mixed type. These patients were also categorized into the following three sub-groups according to their clinical time course: progressive type showing no episodes of vertigo, sequential type showing recurrent vertigo attacks and single-attack type showing a single episode of vertigo. RESULTS: Ten, 11 and 23 patients were classified as the superior, the inferior, and the mixed type, respectively. Seventeen, 23, and four patients were classified as the progressive, the sequential, and the single-attack type, respectively. For the patients having one or more vertigo attacks, the duration of the vertigo attack was longer than 24 h in 69% of the mixed type, and the duration of vertigo in the mixed type was significantly longer than that in the inferior type (p < 0.05). PMID- 26381714 TI - Effects of acute resistance exercise on acyl-ghrelin and obestatin levels in hemodialysis patients: a pilot study. AB - Chronic physical exercises may be beneficial to modulate appetite hormones as acyl-ghrelin (orexigenic) and obestatin (anorexigenic) in chronic kidney disease (CKD) patients; however, there are no data about the effects of acute exercises on these hormones. Thus, the aim of the present study was to assess the effect of acute resistance exercise on appetite hormones (acyl-ghrelin and obestatin) of patients undergoing hemodialysis (HD). Twenty-five patients (44.7 +/- 12.9 years, 68% women) on regular HD program were enrolled into two groups, 16 patients performed exercises and 9 patients comprised the control group. The patients performed the exercises in both lower limbs with ankle-cuffs and elastic bands, 30 min after the initiation of hemodialysis session. Blood samples of both the groups were drawn in the morning before and after 30 min with exercise session (exercise group) and, before and after the same time without exercise (control group). Acyl-ghrelin and obestatin plasma levels were measured using an enzyme immunometric assay. Acyl-ghrelin plasma levels did not change in both the groups. However, when stratified by gender the acyl-ghrelin increased significantly right after exercise in men [32.1 pg/mL (25.6-41.2) to 46.0 pg/mL (39.0-59.5)] (p = 0.04). Obestatin plasma levels reduced after a single bout of exercise and changes remained significantly when the sample was stratified by gender. There was no change in obestatin plasma levels in control group. A single bout of resistance exercise seems to modulate the levels of appetite hormones in HD patients. PMID- 26381715 TI - Does preeclampsia have any adverse effect on fetal heart? AB - OBJECTIVE: To determine whether preeclampsia causes fetal cardiac cell damage by assessing umbilical artery NT-proBNP, cardiac troponin I and homocysteine. METHODS: A cross-sectional study with 73 fetuses between 26 and 40 weeks of gestation was performed. Thirty-three healthy mothers' fetuses were control group (Group I). While 12 mildly pre-eclamptic mothers' fetuses constituted Group II, 28 fetuses of severe pre-eclamptic mothers were Group III. RESULTS: Umbilical cord mean NT-proBNP levels of Group I, II and III are 520.8 +/- 404.5 pg/ml; 664.2 +/- 215.9 pg/ml; and 1932.8 +/- 2979.5 pg/ml, respectively (p = 0.0001). The number of neonates with NT-proBNP > 500 pg/mL that indicates severe cardiac damage is higher in Group III (p = 0.001). The mean homocysteine levels are also statistically significantly higher in Group III. Cardiac troponin I levels are not different between the groups (p = 0.46). CONCLUSION: Increased NT-proBNP and homocysteine might not only indicate some degree of in-utero cardiac cell damage but also feto-placental endothelial injury in the fetuses of severe pre-eclamptic mothers. Our finding that shows no evidence of correlation between cardiac troponin I levels with cell damage and endothelial injury requires further research. PMID- 26381716 TI - Y STR haplotype diversity in central Indian population. AB - AIMS: Seventeen Y-STR loci (DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS385a/b, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS635 and Y GATA-H4) were analysed in 173 males belonging to the central Indian population with the aim of studying genetic diversity and adding to the population database. METHODS: Multiplexed PCR amplifications of the 17 Y STR loci were performed using AmpFlSTR(r) Yfiler(r) Kit. Amplified products were genotyped using a multi capillary electrophoresis with POP-4 polymer in ABI Prism 3100 Genetic Analyzer. Population genetic diversity and allele frequencies were calculated. The haplotype data obtained in the study was compared with the Y-STR haplotypes reference database (YHRD, http://www.yhrd.org ) and with previously published population data using the AMOVA tool and visualised in two-dimensional multidimensional scaling (MDS) plots. RESULTS: A total of 147 haplotypes were observed, out of which 125 were unique. Haplotype diversity and discriminating capacity were found to be 0.9979 and 0.8497, respectively. The gene diversity at the loci ranged from 0.398-0.785. Genotype diversity at the locus DYS385a/b was found to be 0.869. CONCLUSIONS: The population of central India was found to be significantly different (p < 0.05) when compared with populations from other parts of the Indian sub-continent and the population data of other countries. The population data generated in this study are useful for forensic, anthropological and demographic studies. PMID- 26381717 TI - Preclinical safety evaluation of submicronized sildenafil citrate nebulization solution in small experimental animals. AB - PURPOSE: Sildenafil citrate (SC) nebulization solution has the potential to treat pulmonary hypertension by delivering high concentration directly to the respiratory system while minimizing systemic drug exposure and associated toxicity. The objective of the present study was to evaluate the potential toxicity of aerosolized SC (inhaled) in Sprague dawley rats for 28 days. MATERIALS AND METHODS: The rats were randomly divided into five groups (n = 6). Placebo (normal saline) was inhaled to group I (control). Group II was exposed to therapeutic dose (TD): 20 mg/kg, while group 3 and group 4 were exposed to 3 TD and 6 TD, respectively, till 28 days and toxicokinetic parameters were evaluated in group V. The particle size of the nebulized solution of SC (1%) was measured by using Anderson Cascade Impactor. At the end of experiment, all animals were sacrificed. Endpoints used to evaluate potential toxicity of inhaled sildenafil citrate were clinical observations, body weight, and clinical pathology along with broncho-alveolar lavage (BAL) Fluid investigation. RESULTS AND CONCLUSIONS: ACI study has shown that more than 70% aerosolized drug particles were in submicron range (0.3-0.5 MUm). There was no systemic toxicity or clinically limiting local respiratory toxicity associated with inhalation exposure to SC nebulization solution at 6 TD. No significant changes were observed in the level of different blood and BALF parameters in treated groups in comparison to control. Histopathological examination revealed no abnormal findings in the animals of treated group. The data demonstrate that aerosolized sildenafil citrate is well tolerated in rats and suggest its use in humans. PMID- 26381718 TI - CYFRA 21.1 in bronchoalveolar lavage of idiopathic pulmonary fibrosis patients. AB - AIM: Idiopathic pulmonary fibrosis (IPF) is one of the most aggressive forms of interstitial lung diseases, however, clinically relevant biomarkers of diagnosis or prognosis are lacking. In this study, we investigated the levels of a fragment of Cytokeratin 19 (CYFRA 21.1) in bronchoalveolar lavage (BAL) of IPF patients at time of diagnosis. We further evaluated associations between CYFRA 21.1, pulmonary function evolution, mortality, and BAL cell count. MATERIALS AND METHODS: Using the Lumipulse(r) G1200, CYFRA 21.1 was measured in BAL samples of 81 IPF patients and 9 controls. Based upon the median detected level (1.2 ng/mL) of CYFRA 21.1 in IPF patients, they were subdivided into an IPF CYFRA 21.1 low group (<= 1.2 ng/mL) and IPF CYFRA 21.1 high group (> 1.2 ng/mL). RESULTS: The CYFRA 21.1 levels were significantly higher in BAL of IPF patients compared to controls (P = .0015).Worse survival was observed, but no changes in pulmonary function, for IPF patients with high CYFRA 21.1 levels versus patients with low CYFRA 21.1 levels [P = .030, HR: 0.41, (0.18-0.92)[. The CYFRA 21.1 level correlated with both neutrophils (%: R = 0.60, P < .0001; #: R = 0.47, P < .0001) and eosinophils (%: R = 0.38, P = .0005; #: R = 0.30, P < .0072). CONCLUSIONS: CYFRA 21.1 is increased in BAL of IPF patients. IPF patients with a high CYFRA 21.1 concentration have a worse survival. CYFRA 21.1 levels correlate with eosinophils and neutrophils. Further studies are warranted in using CYFRA 21.1 as a biomarker for IPF prognosis. PMID- 26381719 TI - Characterization of inflammation in a rat model of acute lung injury after repeated pulmonary lavage. AB - AIM OF THE STUDY: Repeated pulmonary lavage allows to reliably reproduce failure of gas exchange and major histological findings of acute lung injury (ALI). However, because the capacity of pulmonary lavage to induce pulmonary inflammation is not well established in rodents, this study aims to characterize the induction of pulmonary inflammation in a rat model of ALI. MATERIALS AND METHODS: Male adult rats were divided into a treatment group (n = 9) that received pulmonary lavage with consecutive mechanical ventilation, and a control group that received mechanical ventilation only (n = 9). Arterial blood gas analyses were performed every 30 min throughout the study. Pressure-volume curves, and lung tissue and plasma samples, were obtained at 240 min after the start of mechanical ventilation. Protein content and surface activity of bronchoalveolar lavage fluid was assessed. Transcriptional and translational regulation of pro- and anti-inflammatory cytokines IL-1beta, TNF-alpha, IL-6, and IL-10 was determined in lungs and plasma. Markers of cellular stress were measured in lung tissue. RESULTS: Pulmonary lavage significantly decreased lung compliance, induced hypoxia and hypercapnia, and mediated respiratory acidosis. Protein content of lavage fluid was significantly increased and contained washed out surfactant. Expression of IL-1beta, TNF-alpha, and IL-6 mRNA and protein expression of IL-1beta and TNF-alpha was significantly induced in lavaged lungs, without spillover into the systemic circulation. Markers of cellular stress were significantly upregulated in lavaged lungs. CONCLUSIONS: This model of ALI applied in rats can induce pulmonary inflammation. The model might be used to develop therapeutic strategies that target pulmonary inflammation in ALI. PMID- 26381720 TI - Mixed Mechanism of Lubrication by Lipid Bilayer Stacks. AB - Although the key role of lipid bilayer stacks in biological lubrication is generally accepted, the mechanisms underlying their extreme efficiency remain elusive. In this article, we report molecular dynamics simulations of lipid bilayer stacks undergoing load and shear. When the hydration level is reduced, the velocity accommodation mechanism changes from viscous shear in hydration water to interlayer sliding in the bilayers. This enables stacks of hydrated lipid bilayers to act as efficient boundary lubricants for various hydration conditions, structures, and mechanical loads. We also propose an estimation for the friction coefficient; thanks to the strong hydration forces between lipid bilayers, the high local viscosity is not in contradiction with low friction coefficients. PMID- 26381721 TI - Exploring the dark matter of the human genome using oligonucleotide-based molecules. PMID- 26381723 TI - Properties of a novel polydatin-beta-d-glucosidase from Aspergillus niger SK34.002 and its application in enzymatic preparation of resveratrol. AB - BACKGROUND: Resveratrol and its glucoside polydatin are the main stilbenes in Polygonum cuspidatum. Resveratrol has become the subject of intensive research over the past two decades owing to its outstanding pharmacological properties. However, its lower concentration in plants compared to polydatin limits its application. In this study, the polydatin-beta-d-glucosidase (PBG) that hydrolyzes the beta-d-glucosyl residue of polydatin with release of resveratrol was purified to homogeneity and characterized. RESULTS: The molecular weight of PBG was estimated to be 125 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and 128 kDa by size-exclusion chromatography- multi-angle laser light scattering/ultraviolet/refractive index. The optimal PBG activity was observed at 70 degrees C and pH 4.5. The enzyme showed around 50% stability at 60 degrees C for 12 h and residual activity was over 80% at pH 3.0-5.0. Ca(2+) , Mg(2+) , Mn(2+) , Zn(2+) , Ba(2+) , Ni(2+) , Co(2+) and Cu(2+) ions had no significant effect on the enzyme activity. The PBG presented higher affinity to polydatin (Km = 0.74 mmol L(-1) ) than p-nitrophenyl-beta-d-glucopyranoside (Km = 2.9 mmol L(-1) ) and cellobiose (Km = 8.9 mmol L(-1) ). CONCLUSION: With this enzyme, nearly all polydatin in P. cuspidatum was converted to resveratrol. Although several beta-D-glucosidases (BGLs) have been obtained from other sources, PBG is distinguished from other BGLs by its outstanding thermal stability and high catalytic efficiency. (c) 2015 Society of Chemical Industry. PMID- 26381722 TI - Sex-related differences in small intestinal transit and serotonin dynamics in high-fat-diet-induced obesity in mice. AB - Obesity alters gastrointestinal (GI) motility and 5-HT signalling. Altered 5-HT signalling disrupts control of GI motility. Levels of extracellular 5-HT depend on enterochromaffin (EC) cell release and serotonin transporter (SERT) uptake. We assessed GI transit and 5-HT signalling in the jejunum of normal and obese mice. Male and female mice were fed a control diet (CD; 10% of kilocalories as fat) or a high-fat diet (HFD; 60% of kilocalories as fat). Gastrointestinal transit was increased in male HFD-fed and female CD-fed compared with male CD-fed mice. The 5 HT3 receptor blocker, alosetron, increased gastric emptying in male CD-fed mice, but decreased transit in female CD-fed mice. The 5-HT-induced jejunal longitudinal muscle contractions in vitro were similar in all mice. In contrast to male CD-fed mice, 5-HT uptake (measured using continuous amperometry in vitro) in male HFD-fed mice was fluoxetine insensitive, yet sensitive to cocaine and the dopamine transporter (DAT) blocker GBR 12909. Immunoreactivity for DAT was present in the mucosa, and protein levels were greater in male HFD-fed compared with CD-fed mice. Extracellular 5-HT and mucosal 5-hydroxyindolacetic acid (5-HT metabolite) were similar in male HFD-fed compared with CD-fed mice. 5 Hydroxytryptamine uptake was fluoxetine sensitive in all females. Greater SERT protein, decreased extracellular 5-HT and greater mucosal 5-hydroxyindolacetic acid were observed in female HFD-fed compared with CD-fed mice. Mucosal 5-HT and EC cell numbers were similar in CD-fed and HFD-fed mice of both sexes; female 5 HT and EC cell numbers were increased compared with males. The HFD did not alter plasma sex hormone levels in any mice. Overall, obesity alters GI transit and 5 HT signalling in a sex-dependent manner. PMID- 26381724 TI - Persistent Diarrhea after Celiac Plexus Block in a Pancreatic Cancer Patient: Case Report and Literature Review. AB - BACKGROUND: Neurolytic celiac plexus block is increasingly used to treat refractory pain associated with abdominal malignancies, especially pancreatic cancer. While self-limiting diarrhea can occur commonly in patients post procedure, a very rare risk of persistent diarrhea exists. OBJECTIVE: We present a case of a 70 year old female with locally advanced pancreatic adenocarcinoma who was hospitalized for persistent severe diarrhea post celiac plexus block and discuss management options for this adverse effect. DESIGN: A review of the current literature within the past 20 years (PubMed and Ovid databases) was conducted to discuss alternatives of management. MEASUREMENTS/RESULTS: Ninety three entries were found in total including duplicates and only two were included for relevance. Management options that were discussed included anti-motility agents, alpha-adrenergic agonists, and somastatin analog (octreotide). Our patient was initially treated with loperamide, hyoscine, psyllium, and cholestyramine before responding to octreotide. The patient was discharged on long-acting octreotide after her bowel routine stabilized. CONCLUSIONS: Persistent diarrhea is a very rare complication of celiac plexus block and current literature regarding proper management is based largely on anecdotal evidence. For this patient octreotide was an effective agent for the management of this complication. PMID- 26381725 TI - Vagus Nerve and Vagus Nerve Stimulation, a Comprehensive Review: Part II. AB - The development of vagus nerve stimulation (VNS) began in the 19th century. Although it did not work well initially, it introduced the idea that led to many VNS-related animal studies for seizure control. In the 1990s, with the success of several early clinical trials, VNS was approved for the treatment of refractory epilepsy, and later for the refractory depression. To date, several novel electrical stimulating devices are being developed. New invasive devices are designed to automate the seizure control and for use in heart failure. Non invasive transcutaneous devices, which stimulate auricular VN or carotid VN, are also undergoing clinical trials for treatment of epilepsy, pain, headache, and others. Noninvasive VNS (nVNS) exhibits greater safety profiles and seems similarly effective to their invasive counterpart. In this review, we discuss the history and development of VNS, as well as recent progress in invasive and nVNS. PMID- 26381726 TI - Spirally-patterned pinhole arrays for long-term fluorescence cell imaging. AB - Fluorescence cell imaging using a fluorescence microscope is an extensively used technique to examine the cell nucleus, internal structures, and other cellular molecules with fluorescence response time and intensity. However, it is difficult to perform high resolution cell imaging for a long period of time with this technique due to necrosis and apoptosis depending on the type and subcellular location of the damage caused by phototoxicity. A large number of studies have been performed to resolve this problem, but researchers have struggled to meet the challenge between cellular viability and image resolution. In this study, we employ a specially designed disc to reduce cell damage by controlling total fluorescence exposure time without deterioration of the image resolution. This approach has many advantages such as, the apparatus is simple, cost-effective, and easily integrated into the optical pathway through a conventional fluorescence microscope. PMID- 26381728 TI - Updates in perioperative medicine. AB - BACKGROUND: As our surgical population becomes older and more medically complex, knowledge of the most recent perioperative literature is necessary to optimize perioperative care. We aim to summarize and critique literature published over the past year with the highest potential to impact the clinical practice of perioperative medicine. METHODS: We reviewed articles published between January 2014 and April 2015, identified via MEDLINE search. The final 10 articles selected were determined by consensus among all authors, with criteria for inclusion including scientific rigor and relevance to perioperative medicine practice. RESULTS: Key findings include: long term beta-blockade should be continued prior to surgery, routine screening with postoperative troponin is not recommended, initiation/continuation of aspirin or clonidine in the perioperative period is not beneficial and may increase adverse outcomes, preoperative diagnosis and treatment of obstructive sleep apnea may reduce risk of postoperative cardiovascular complications, new pulmonary risk indices are available that accurately estimate postoperative pulmonary complications, postoperative atrial fibrillation is associated with increased long-term stroke risk, risk scores such as the CHADS2 (Congestive heart failure, Hypertension, Age >=75 years, Diabetes Mellitus, previous stroke or transient ischemic attack) are superior to the Revised Cardiac Risk Index in predicting adverse postoperative outcomes for patients with nonvalvular atrial fibrillation, and utilization of bridging anticoagulation comes with a much higher risk of bleeding compared to patients who are not bridged. CONCLUSIONS: The body of literature reviewed provides important information for clinicians caring for surgical patients across multiple fronts, including preoperative risk assessment, medication management, and postoperative medical care. PMID- 26381727 TI - Activation of extracellular regulated kinase and mechanistic target of rapamycin pathway in focal cortical dysplasia. AB - Neuropathology of resected brain tissue has revealed an association of focal cortical dysplasia (FCD) with drug-resistant epilepsy (DRE). Recent studies have shown that the mechanistic target of rapamycin (mTOR) pathway is hyperactivated in FCD as evidenced by increased phosphorylation of the ribosomal protein S6 (S6) at serine 240/244 (S(240/244) ), a downstream target of mTOR. Moreover, extracellular regulated kinase (ERK) has been shown to phosphorylate S6 at serine 235/236 (S(235/236) ) and tuberous sclerosis complex 2 (TSC2) at serine 664 (S(664) ) leading to hyperactive mTOR signaling. We evaluated ERK phosphorylation of S6 and TSC2 in two types of FCD (FCD I and FCD II) as a candidate mechanism contributing to mTOR pathway dysregulation. Tissue samples from patients with tuberous sclerosis (TS) served as a positive control. Immunostaining for phospho S6 (pS6(240/244) and pS6(235/236) ), phospho-ERK (pERK), and phospho-TSC2 (pTSC2) was performed on resected brain tissue with FCD and TS. We found increased pS6(240/244) and pS6(235/236) staining in FCD I, FCD II and TS compared to normal appearing tissue, while pERK and pTSC2 staining was increased only in FCD IIb and TS tissue. Our results suggest that both the ERK and mTOR pathways are dysregulated in FCD and TS; however, the signaling alterations are different for FCD I as compared to FCD II and TS. PMID- 26381729 TI - Undercarboxylated osteocalcin as a biomarker of subclinical atherosclerosis in non-dialysis patients with chronic kidney disease. AB - BACKGROUND: Studies in recent years have shown that undercarboxylated osteocalcin (uOC) not only maintains bone mineralization, but is also involved in the regulation of atherosclerosis. However, a correlation between uOC and carotid atherosclerosis in non-dialysis patients with chronic kidney disease (CKD) has not been investigated. A total of 240 non-dialysis patients with CKD were included in the study. For these patients, the median estimated glomerular filtration rate (eGFR) was 20.05 (12.43-49.32) ml/min/1.73m(2). Serum uOC levels were measured using enzyme-linked immunosorbent assay (ELISA). Carotid ultrasonography was performed to assess carotid atherosclerotic plaques and intima-media thickness (IMT) in an attempt to analyze the relationship between uOC level and carotid atherosclerosis. RESULTS: The uOC levels of non-dialysis patients with CKD were significantly lower than those of healthy controls [28.16 (21.40-45.85) ng/mL vs. 36.42 (28.05-49.28) ng/mL, P < 0.01]. The uOC levels gradually decreased as CKD progressed (P < 0.01). The uOC levels were significantly lower in patients with carotid plaques than in patients without carotid plaques [25.98 (20.14-31.35) ng/mL vs. 31.02 (25.86-36.40) ng/mL, P < 0.01]. uOC level showed significant negative correlation with IMT (r = -0.33, P < 0.01). Logistic regression analysis revealed that after adjustment for various confounding factors, decreased uOC levels were shown to indicate increased possibility of carotid atherosclerotic plaque development in non-dialysis patients with CKD (on every 1 SD decrease in the uOC level, odds ratio 1.70, 95 % confidence interval 1.24-2.98, P < 0.01). Multivariate stepwise regression analysis demonstrated that decreased uOC level (beta = -0.163, P < 0.05) was an independent risk factor for increased carotid IMT in non-dialysis patients with CKD. CONCLUSION: Serum uOC levels in non-dialysis patients with CKD are significantly lower than those in healthy individuals, and uOC is closely associated with subclinical atherosclerosis in CKD patients. PMID- 26381730 TI - Age-related variation in the mechanical properties of foods processed by Sapajus libidinosus. AB - OBJECTIVES: The diet of tufted capuchins (Sapajus) is characterized by annual or seasonal incorporation of mechanically protected foods. Reliance on these foods raises questions about the dietary strategies of young individuals that lack strength and experience to access these resources. Previous research has demonstrated differences between the feeding competencies of adult and juvenile tufted capuchins. Here we test the hypothesis that, compared to adults, juveniles will process foods with lower toughness and elastic moduli. MATERIALS AND METHODS: We present data on variation in the toughness and elastic modulus of food tissues processed by Sapajus libidinosus during the dry season at Fazenda Boa Vista, Brazil. Food mechanical property data were collected using a portable universal mechanical tester. RESULTS: Results show that food tissues processed by the capuchins showed significant differences in toughness and stiffness. However, we found no relationship between an individual's age and mean or maximum food toughness or elastic modulus, indicating both juvenile and adult S. libidinosus are able to process foods of comparable properties. DISCUSSION: Although it has been suggested that juveniles avoid mechanically protected foods, age-related differences in feeding competence are not solely due to variation in food toughness or stiffness. Other factors related to food type (e.g., learning complex behavioral sequences, achieving manual dexterity, obtaining physical strength to lift stone tools, or recognizing subtle cues about food state) combined with food mechanical properties better explain variation in juvenile feeding competency. PMID- 26381731 TI - Inverting the pyramid! Extent and quality of food advertised on Austrian television. AB - BACKGROUND: Research showed that food marketing for children frequently contradicts national dietary guidelines. Children, unlike adults, are not able to understand the persuasiveness of the advertisements with its short- and long-term effects on health, thus the common international tenor is to restrict food marketing. In the European Union, marketing restriction based on self-regulation have been initiated (EU Pledge Nutrition Criteria). The study aims contribute to depict the status quo of television advertisement targeted at children before the pledged initiative came into full effect. METHODS: In this study we analyze the quality and displaying frequency of a set of advertisements targeted at children broadcasted on Austrian television. Promoted food products targeted at children or adults were identified. Category-based analysis of the displayed food was performed based on the Austrian Nutrition guidelines (number of displayed food per food category). The children's food content was analyzed according to the newly established nutritional quality criteria for advertised food in the EU to assess the nutritional quality of the depicted food. RESULTS: In total, 360 h of video material was recorded in February and March 2014. A set of 1919 food advertisements, with 15.1 % targeted at children were broadcasted. Of all food advertisements targeted at children, 92.4 % was for fatty, sweet and salty snacks, while no advertisements for vegetables, legumes or fruits were shown. From all food advertisements for children, 65.9 % originated from participating companies of the EU Pledge Nutrition Criteria. Further analysis revealed that 95.9 % of the advertised food for children showed at least one aspect of nonconformity with the EU Pledge Nutrition Criteria; on the contrary 64.7 % of the displayed food advertisement also featured at least one desirable food component (e.g. high fibre content, high protein content). CONCLUSIONS: The present research suggests that the majority of advertised food for children do not conform with the pledged criteria as defined in the EU Pledge Nutrition Criteria and almost all advertisements would be prohibited. We discuss our findings in the context of public health nutrition and present a perspective for future directions in this important field of research. PMID- 26381732 TI - Self-administered version of the Fabry-associated pain questionnaire for adult patients. AB - BACKGROUND: Fabry-associated pain may be the first symptom of Fabry disease (FD) and presents with a unique phenotype including mostly acral burning triggerable pain attacks, evoked pain, pain crises, and permanent pain. We recently developed and validated the first Fabry Pain Questionnaire (FPQ) for adult patients. Here we report on the validation of the self-administered version of the FPQ that no longer requires a face-to-face interview but can be filled in by the patients themselves allowing more flexible data collection. METHODS: At our Wurzburg Fabry Center for Interdisciplinary Treatment, Germany, we have developed the self administered version of the FPQ by adapting the questionnaire to a self-report version. To do this, consecutive Fabry patients with current or past pain history (n = 56) were first interviewed face-to-face. Two weeks later patients' self reported questionnaire results were collected by mail (n = 55). We validated the self-administered version of the FPQ by assessing the inter-rater reliability agreement of scores obtained by supervised administration and self-administration of the FPQ. RESULTS: The FPQ contains 15 questions on the different pain phenotypes, on pain development during life with and without therapy, and on impairment due to pain. Statistical analysis showed that the majority of questions were answered in high agreement in both sessions with a mean AC1 statistic of 0.857 for 55 nominal-scaled items and a mean ICC of 0.587 for 9 scores. CONCLUSIONS: This self-administered version of the first pain questionnaire for adult Fabry patients is a useful tool to assess Fabry associated pain without a time-consuming face-to-face interview but via a self reporting survey allowing more flexible usage. PMID- 26381733 TI - Analgesic effect of cathodal transcranial current stimulation over right dorsolateral prefrontal cortex in subjects with muscular temporomandibular disorders: study protocol for a randomized controlled trial. AB - BACKGROUND: Temporomandibular disorders are a group of orofacial pain conditions that are commonly identified in the general population. Like many other chronic pain conditions, they can be associated with anxiety/depression, which can be related to changes in the activity of the dorsolateral prefrontal cortex. Some studies have demonstrated clinical improvement in subjects with chronic pain who are given therapeutic neuromodulation. Transcranial direct current stimulation is a noninvasive brain stimulation technique that allows the modulation of neuronal membranes. This therapy can enhance or inhibit action potential generation in cortical neurons. In some instances, medications acting in the central nervous system may be helpful despite their adverse side effects. It is important to determine if cathodal transcranial direct current stimulation over the dorsolateral prefrontal cortex, an area that modulates emotion and motor cortex excitability, has an analgesic effect on chronic temporomandibular disorders pain. METHOD/DESIGN: The investigators will run a randomized, controlled crossover double blind study with 15 chronic muscular temporomandibular disorder subjects. Each subject will undergo active (1 mA and 2 mA) and sham transcranial direct current stimulation. Inclusion criteria will be determined by the Research Diagnostic Criteria for Temporomandibular Disorders questionnaire, with subjects who have a pain visual analogic scale score of greater than 4/10 and whose pain has been present for the previous 6 months, and with a State-Trait Anxiety Inventory score of more than 42. The influence of transcranial direct current stimulation will be assessed through a visual analogic scale, quantitative sensory testing, quantitative electroencephalogram, and the State-Trait Anxiety Inventory score. DISCUSSION: Some studies have demonstrated a strong association between anxiety/depression and chronic pain, where one may be the cause of the other. This is especially true in chronic temporomandibular disorders, and breaking this cycle may have an effect over the symptoms and associated dysfunction. We believe that by inhibiting activity of the dorsolateral prefrontal cortex though cathodal transcranial direct current stimulation, there may be a change in both anxiety/depression and pain level. Transcranial direct current stimulation may emerge as a new tool to be considered for managing these patients. We envision that the information obtained from this study will provide a better understanding of the management of chronic temporomandibular disorders. TRIAL REGISTRATION: This trial was registered at clinicaltrials.gov on 24 May 2014 (Identifier: NCT02152267 ). PMID- 26381734 TI - Innovation in Health Policy Education: Project-Based Service Learning at a Distance for Graduate Midwifery Students. AB - Core competencies for midwifery practice include an understanding of systems of health care delivery and advocacy for legislation and policy initiatives that promote quality in health care. Today's rapidly changing health care environment, due in part to the implementation of the Patient Protection and Affordable Care Act, mandates that midwives possess greater literacy in health policy and comfort with political action than ever before. Frequently disinterested in politics and intimidated by the policymaking process, student midwives lack the foundational knowledge and practical skills needed to meet this professional obligation. The Midwifery Institute of Philadelphia University graduate program educates both student nurse-midwives and student midwives in health policy using an innovative, project-based service-learning approach featuring real-world collaborative experiences. This novel teaching style is ideally suited for instruction at a distance because of the diversity of experience brought to the virtual classroom by students in widely disparate geopolitical locations. As students accomplish measurable objectives within their individually developed projects and reflect with classmates about their experiences, they feel empowered to effect change and report lower perceived barriers to future political engagement. PMID- 26381736 TI - Pharmacodynamic Effects When Clopidogrel is Given Before Cangrelor Discontinuation. AB - OBJECTIVE: To determine whether initiation of clopidogrel before discontinuation of cangrelor would impact on the recovery of platelet reactivity. BACKGROUND: The active metabolite of clopidogrel cannot bind to P2Y12 when cangrelor occupies the receptor. Pharmacodynamic studies have shown that this interaction is avoided when clopidogrel is given at the end of the cangrelor infusion. We found that antiplatelet effects of another thienopyridine, prasugrel, were apparent when prasugrel was administered 0.5 hour before cangrelor was stopped. METHODS: Platelet function studies (light transmission aggregometry, VerifyNow, and flow cytometry) were performed on blood from patients with stable coronary artery disease who were taking aspirin when a loading dose of clopidogrel (600 mg) was given during a cangrelor infusion (0.5 and 1 hour before cangrelor was stopped). Results were compared with those obtained when clopidogrel was given immediately after cangrelor was stopped. RESULTS: Administration of clopidogrel 0.5 and 1 hour before discontinuation of the cangrelor infusion did not prevent recovery of platelet reactivity more effectively than administration at the end of the infusion. CONCLUSION: Our results support the previously established strategy of administering clopidogrel immediately after discontinuation of cangrelor. Earlier administration increases the recovery of platelet function. PMID- 26381735 TI - Genomic profiling of a Hepatocyte growth factor-dependent signature for MET targeted therapy in glioblastoma. AB - BACKGROUND: Constitutive MET signaling promotes invasiveness in most primary and recurrent GBM. However, deployment of available MET-targeting agents is confounded by lack of effective biomarkers for selecting suitable patients for treatment. Because endogenous HGF overexpression often causes autocrine MET activation, and also indicates sensitivity to MET inhibitors, we investigated whether it drives the expression of distinct genes which could serve as a signature indicating vulnerability to MET-targeted therapy in GBM. METHODS: Interrogation of genomic data from TCGA GBM (Student's t test, GBM patients with high and low HGF expression, p <= 0.00001) referenced against patient-derived xenograft (PDX) models (Student's t test, sensitive vs. insensitive models, p <= 0.005) was used to identify the HGF-dependent signature. Genomic analysis of GBM xenograft models using both human and mouse gene expression microarrays (Student's t test, treated vs. vehicle tumors, p <= 0.01) were performed to elucidate the tumor and microenvironment cross talk. A PDX model with EGFR(amp) was tested for MET activation as a mechanism of erlotinib resistance. RESULTS: We identified a group of 20 genes highly associated with HGF overexpression in GBM and were up- or down-regulated only in tumors sensitive to MET inhibitor. The MET inhibitors regulate tumor (human) and host (mouse) cells within the tumor via distinct molecular processes, but overall impede tumor growth by inhibiting cell cycle progression. EGFR (amp) tumors undergo erlotinib resistance responded to a combination of MET and EGFR inhibitors. CONCLUSIONS: Combining TCGA primary tumor datasets (human) and xenograft tumor model datasets (human tumor grown in mice) using therapeutic efficacy as an endpoint may serve as a useful approach to discover and develop molecular signatures as therapeutic biomarkers for targeted therapy. The HGF dependent signature may serve as a candidate predictive signature for patient enrollment in clinical trials using MET inhibitors. Human and mouse microarrays maybe used to dissect the tumor-host interactions. Targeting MET in EGFR (amp) GBM may delay the acquired resistance developed during treatment with erlotinib. PMID- 26381737 TI - Povidone-iodine hand wash and hand rub products demonstrated excellent in vitro virucidal efficacy against Ebola virus and modified vaccinia virus Ankara, the new European test virus for enveloped viruses. AB - BACKGROUND: The recent Ebola virus (EBOV) epidemic highlights the need for efficacious virucidal products to help prevent infection and limit the spread of Ebola virus disease. However, there is limited data on the efficacy of virucidal products against EBOV, because the virus has a high biosafety level and is only available in a few laboratories worldwide. The virucidal efficacy of antiseptics and disinfectants can be determined using the European Standard EN14476:2013/FprA1:2015. Modified vaccinia virus Ankara (MVA) was introduced in 2014 as a reference virus for the claim 'virucidal active against enveloped viruses for hygienic hand rub and hand wash'. For EBOV, also an enveloped virus, the suitability of MVA as a surrogate needs to be proven. The aim of this study was to test the in vitro efficacy of four povidone iodine (PVP-I) formulations against EBOV: 4% PVP-I skin cleanser; 7.5% PVP-I surgical scrub; 10% PVP-I solution; and 3.2% PVP-I and 78% alcohol solution. The formulations were tested with MVA to define the test conditions, and as a secondary objective the suitability of MVA as a surrogate for enveloped viruses like EBOV was assessed. METHODS: According to EN14476, a standard suspension test was used for MVA. Large volume plating was used for EBOV to increase test sensitivity and exclude potential after-effects. All products were tested under clean (0.3 g/L BSA) and dirty (3.0 g/L BSA + 3.0 mL/L erythrocytes) conditions with MVA for 15, 30, and 60 s. The concentration-contact time values obtained with MVA were verified for EBOV. RESULTS: Viral titres of MVA and EBOV were reduced by >99.99% to >99.999% under clean and dirty conditions after application of the test products for 15 seconds. CONCLUSIONS: All products showed excellent virucidal efficacy against EBOV, demonstrating the important role PVP-I can play in helping to prevent and limit the spread of Ebola virus disease. The efficacy against both test viruses after 15 s is helpful information for the implementation of guidance for people potentially exposed to EBOV, and confirms the excellent virucidal efficacy of PVP I against enveloped viruses. MVA was found to be a suitable surrogate for enveloped viruses like EBOV. PMID- 26381738 TI - The mitochondrial genome of Angiostrongylus mackerrasae as a basis for molecular, epidemiological and population genetic studies. AB - BACKGROUND: Angiostrongylus mackerrasae is a metastrongyloid nematode endemic to Australia, where it infects the native bush rat, Rattus fuscipes. This lungworm has an identical life cycle to that of Angiostrongylus cantonensis, a leading cause of eosinophilic meningitis in humans. The ability of A. mackerrasae to infect non-rodent hosts, specifically the black flying fox, raises concerns as to its zoonotic potential. To date, data on the taxonomy, epidemiology and population genetics of A. mackerrasae are unknown. Here, we describe the mitochondrial (mt) genome of A. mackerrasae with the aim of starting to address these knowledge gaps. METHODS: The complete mitochondrial (mt) genome of A. mackerrasae was amplified from a single morphologically identified adult worm, by long-PCR in two overlapping amplicons (8 kb and 10 kb). The amplicons were sequenced using the MiSeq Illumina platform and annotated using an in-house pipeline. Amino acid sequences inferred from individual protein coding genes of the mt genomes were concatenated and then subjected to phylogenetic analysis using Bayesian inference. RESULTS: The mt genome of A. mackerrasae is 13,640 bp in size and contains 12 protein coding genes (cox1-3, nad1-6, nad4L, atp6 and cob), and two ribosomal RNA (rRNA) and 22 transfer RNA (tRNA) genes. CONCLUSIONS: The mt genome of A. mackerrasae has similar characteristics to those of other Angiostrongylus species. Sequence comparisons reveal that A. mackerrasae is closely related to A. cantonensis and the two sibling species may have recently diverged compared with all other species in the genus with a highly specific host selection. This mt genome will provide a source of genetic markers for explorations of the epidemiology, biology and population genetics of A. mackerrasae. PMID- 26381739 TI - Hsp27 Acts as a Master Molecular Chaperone and Plays an Essential Role in Hepatocellular Carcinoma Progression. AB - AIMS: Hsp27, a master molecular chaperone, plays an important role in cancer. However, the specific co-chaperones that partner with Hsp27 and the role of Hsp27 in hepatocellular carcinoma (HCC) are not fully enumerated. The present study focuses on the role of Hsp27 in HCC and explores its potential co-chaperones in HCC development. METHODS: Gene overexpression or knockdown was used to observe the role of Hsp27 in HCC. Co-immunoprecipitation and mass spectrometry were used to explore apoptosis resistance by regulating multiple co-chaperones of Hsp27. Hsp27 protein-protein interaction (PPI) networks were constructed by the MetaCore software. RESULTS: Hsp27 was upregulated in HCC tissues, and Hsp27 overexpression significantly facilitated formation of HCC cell colony and invasion in normoxia and tolerance in hypoxia by interacting with HIF-1alpha. Next, the analysis of microarrays revealed that Hsp27 regulated several cellular signaling pathways, including Wnt, ErbB and TGF-beta signaling. Moreover, we characterized the Hsp27 PPI map, which indicated that Hsp27 along with its co-chaperones formed different complexes and exerts transcription regulation activity by activating sp1, c-Myc, p53 and ESR1. CONCLUSIONS: Hsp27 along with its co-chaperones was related to the development of HCC by regulating multiple signaling pathways, and drugs that target Hsp27 along with its co-chaperones may be a potential therapy for HCC. PMID- 26381740 TI - The impact of polymer coatings on magnetite nanoparticles performance as MRI contrast agents: a comparative study. AB - BACKGROUND: Superparamagnetic iron oxide nanoparticles (SPIONs) are the most commonly used negative MRI contrast agent which affect the transverse (T2) relaxation time. The aim of the present study was to investigate the impact of various polymeric coatings on the performance of magnetite nanoparticles as MRI contrast agents. METHODS: Ferrofluids based on magnetite (Fe3O4) nanoparticles (SPIONs) were synthesized via chemical co-precipitation method and coated with different biocompatible polymer coatings including mPEG-PCL, chitosan and dextran. RESULTS: The bonding status of different polymers on the surface of the magnetite nanoparticles was confirmed by the Fourier transform infrared spectroscopy (FT-IR) and thermogravimetric analysis (TGA). The vibrating sample magnetometer (VSM) analysis confirmed the superparamagnetic behavior of all synthesized nanoparticles. The field-emission scanning electron microscopy (FE SEM) indicated the formation of quasi-spherical nanostructures with the final average particle size of 12-55 nm depending on the type of polymer coating, and X ray diffraction (XRD) determined inverse spinel structure of magnetite nanoparticles. The ferrofluids demonstrated sufficient colloidal stability in deionized water with the zeta potentials of -24.2, -16.9, +31.6 and -21 mV for the naked SPIONs, and for dextran, chitosan and mPEG-PCL coated SPIONs, respectively. Finally, the magnetic relaxivities of water based ferrofluids were measured on a 1.5 T clinical MRI instrument. The r2/r1 value was calculated to be 17.21, 19.42 and 20.71 for the dextran, chitosan and mPEG-PCL coated SPIONs, respectively. CONCLUSIONS: The findings demonstrated that the value of r2/r1 ratio of mPEG-PCL modified SPIONs is higher than that of some commercial contrast agents. Therefore, it can be considered as a promising candidate for T2 MRI contrast agent. PMID- 26381741 TI - The Association between Multisite Near-Infrared Spectroscopy and Routine Hemodynamic Measurements in Relation to Short-Term Outcome in Preterms with Clinical Sepsis. AB - BACKGROUND: The added clinical value of multisite near-infrared spectroscopy (NIRS) monitoring to detect low organ tissue perfusion in preterm infants at risk of circulatory failure remains unclear. OBJECTIVES: To evaluate the associations between multisite NIRS measurements and clinical signs of circulatory failure in relation to short-term outcome in preterm infants with clinical sepsis. METHODS: Prospective cohort study of preterm infants (gestational age <32 weeks) with clinical sepsis. We monitored cerebral, renal, and intestinal oxygen saturation using NIRS for 72 h following sepsis workup and calculated fractional tissue oxygen extraction (FTOE). We recorded clinical signs of circulatory failure every 8 h. We analyzed the associations between FTOE values, clinical signs of circulatory failure, and short-term outcome. RESULTS: In 28 preterm infants with clinical sepsis, intraindividual and interindividual associations between NIRS values and clinical signs of circulatory failure were weak. At several points of time during the study period, cerebral and renal FTOE were higher in infants who developed intestinal complications compared with infants who did not, while clinical signs of circulatory failure never differed between groups. After correcting for multiple testing, significant differences disappeared. CONCLUSIONS: The associations between multisite FTOE values and clinical signs of circulatory failure were weak in preterm infants with clinical sepsis. Nevertheless, in contrast to clinical signs of circulatory failure, cerebral and renal FTOE values were associated with adverse short-term intestinal outcome in the uncorrected analyses. Multisite NIRS monitoring might help to detect critically low tissue oxygen delivery leading to adverse intestinal outcome not detected by routine hemodynamic measurements. PMID- 26381742 TI - A Conjugate Gradient Algorithm with Function Value Information and N-Step Quadratic Convergence for Unconstrained Optimization. AB - It is generally acknowledged that the conjugate gradient (CG) method achieves global convergence--with at most a linear convergence rate--because CG formulas are generated by linear approximations of the objective functions. The quadratically convergent results are very limited. We introduce a new PRP method in which the restart strategy is also used. Moreover, the method we developed includes not only n-step quadratic convergence but also both the function value information and gradient value information. In this paper, we will show that the new PRP method (with either the Armijo line search or the Wolfe line search) is both linearly and quadratically convergent. The numerical experiments demonstrate that the new PRP algorithm is competitive with the normal CG method. PMID- 26381743 TI - Structure and Stability of Telocentric Chromosomes in Wheat. AB - In most eukaryotes, centromeres assemble at a single location per chromosome. Naturally occurring telocentric chromosomes (telosomes) with a terminal centromere are rare but do exist. Telosomes arise through misdivision of centromeres in normal chromosomes, and their cytological stability depends on the structure of their kinetochores. The instability of telosomes may be attributed to the relative centromere size and the degree of completeness of their kinetochore. Here we test this hypothesis by analyzing the cytogenetic structure of wheat telosomes. We used a population of 80 telosomes arising from the misdivision of the 21 chromosomes of wheat that have shown stable inheritance over many generations. We analyzed centromere size by probing with the centromere specific histone H3 variant, CENH3. Comparing the signal intensity for CENH3 between the intact chromosome and derived telosomes showed that the telosomes had approximately half the signal intensity compared to that of normal chromosomes. Immunofluorescence of CENH3 in a wheat stock with 28 telosomes revealed that none of the telosomes received a complete CENH3 domain. Some of the telosomes lacked centromere specific retrotransposons of wheat in the CENH3 domain, indicating that the stability of telosomes depends on the presence of CENH3 chromatin and not on the presence of CRW repeats. In addition to providing evidence for centromere shift, we also observed chromosomal aberrations including inversions and deletions in the short arm telosomes of double ditelosomic 1D and 6D stocks. The role of centromere-flanking, pericentromeric heterochromatin in mitosis is discussed with respect to genome/chromosome integrity. PMID- 26381744 TI - Association of Self-Reported Frailty with Falls and Fractures among Patients New to Dialysis. AB - BACKGROUND: Although frailty has been linked to higher risk of falls and fracture in the general population, only few studies have examined the extent to which frailty is associated with these outcomes among patients with end-stage renal disease, who are at particularly high risk for these events. METHODS: A total of 1,646 patients who were beginning maintenance hemodialysis in 297 dialysis units throughout the United States from September 2005 to June 2007 were enrolled in the Comprehensive Dialysis Study, and 1,053 Medicare beneficiaries were included in this study. Self-reported frailty was defined by the patients endorsing 2 or more of the following: poor physical functioning, exhaustion or low physical activity. Falls and fractures requiring medical attention were identified through Medicare claims data. We examined the association between frailty and the time to first fall or fracture using the Fine-Gray modification of Cox proportional hazards regression, adjusted for demographics, Quetelet's body mass index, diabetes mellitus, heart failure and atherosclerosis. RESULTS: Seventy-seven percent of patients were frail by self-report. The median length of follow-up was 2.5 (1.0-3.9) years. Crude rates of first medically urgent falls or fractures were 66 and 126 per 1,000 person-years in non-frail and self-reported frail participants, respectively. After accounting for demographic factors, comorbidities and the competing risk of death, self-reported frailty was associated with a higher risk of falls or fractures requiring medical attention (hazards ratio 1.60, 95% CI 1.16-2.20). CONCLUSION: Participants reporting frailty experienced nearly twice the risk of medically urgent falls or fractures compared to those who did not report frailty. PMID- 26381745 TI - A Life-Cycle Model of Human Social Groups Produces a U-Shaped Distribution in Group Size. AB - One of the central puzzles in the study of sociocultural evolution is how and why transitions from small-scale human groups to large-scale, hierarchically more complex ones occurred. Here we develop a spatially explicit agent-based model as a first step towards understanding the ecological dynamics of small and large scale human groups. By analogy with the interactions between single-celled and multicellular organisms, we build a theory of group lifecycles as an emergent property of single cell demographic and expansion behaviours. We find that once the transition from small-scale to large-scale groups occurs, a few large-scale groups continue expanding while small-scale groups gradually become scarcer, and large-scale groups become larger in size and fewer in number over time. Demographic and expansion behaviours of groups are largely influenced by the distribution and availability of resources. Our results conform to a pattern of human political change in which religions and nation states come to be represented by a few large units and many smaller ones. Future enhancements of the model should include decision-making rules and probabilities of fragmentation for large-scale societies. We suggest that the synthesis of population ecology and social evolution will generate increasingly plausible models of human group dynamics. PMID- 26381747 TI - Double-barreled and Concentric Microelectrodes for Measurement of Extracellular Ion Signals in Brain Tissue. AB - Electrical activity in the brain is accompanied by significant ion fluxes across membranes, resulting in complex changes in the extracellular concentration of all major ions. As these ion shifts bear significant functional consequences, their quantitative determination is often required to understand the function and dysfunction of neural networks under physiological and pathophysiological conditions. In the present study, we demonstrate the fabrication and calibration of double-barreled ion-selective microelectrodes, which have proven to be excellent tools for such measurements in brain tissue. Moreover, so-called "concentric" ion-selective microelectrodes are also described, which, based on their different design, offer a far better temporal resolution of fast ion changes. We then show how these electrodes can be employed in acute brain slice preparations of the mouse hippocampus. Using double-barreled, potassium-selective microelectrodes, changes in the extracellular potassium concentration ([K+]o) in response to exogenous application of glutamate receptor agonists or during epileptiform activity are demonstrated. Furthermore, we illustrate the response characteristics of sodium-sensitive, double-barreled and concentric electrodes and compare their detection of changes in the extracellular sodium concentration ([Na+]o) evoked by bath or pressure application of drugs. These measurements show that while response amplitudes are similar, the concentric sodium microelectrodes display a superior signal-to-noise ratio and response time as compared to the double-barreled design. Generally, the demonstrated procedures will be easily transferable to measurement of other ions species, including pH or calcium, and will also be applicable to other preparations. PMID- 26381748 TI - Patients with giant cell arteritis have a lower prevalence of diabetes mellitus: A systematic review and meta-analysis. AB - OBJECTIVE: The aim of this study is to compare the prevalence of diabetes mellitus (DM) in patients who are recently diagnosed with giant cell arteritis (GCA) with age- and sex-matched controls. METHODS: We conducted a systematic review and meta-analysis of observational studies that (1) consisted of GCA cohort and non-GCA cohort that was randomly selected from the same population and (2) provided prevalences of DM at the time of diagnosis for patients with GCA and at the index date for controls. Pooled odds ratios and 95% confidence intervals (CIs) were calculated using a random-effect, Mantel-Haenszel analysis. RESULTS: Five studies with 903 patients with GCA and 1064 controls were identified and included in our data analysis. We demonstrated a statistically significant lower prevalence of DM among patients with GCA with the pooled OR of 0.74 (95% CI, 0.57 0.97). CONCLUSION: At diagnosis, patients with GCA had a lower prevalence of DM. Whether DM could be a protective factor against the development of GCA needs further investigations. PMID- 26381746 TI - Trends in Expanded-Spectrum Cephalosporin-Resistant Escherichia coli and Klebsiella pneumoniae among Dutch Clinical Isolates, from 2008 to 2012. AB - We investigated time trends in extended-spectrum cephalosporin-resistant Escherichia coli and Klebsiella pneumoniae isolates from different patient settings in The Netherlands from 2008-2012. E. coli and K. pneumoniae isolates from blood and urine samples of patients > = 18 years were selected from the Dutch Infectious Disease Surveillance System-Antimicrobial Resistance (ISIS-AR) database. We used multivariable Poisson regression to study the rate per year of blood stream infections by susceptible and resistant isolates, and generalized estimating equation (GEE) log-binomial regression for trends in the proportion of extended-spectrum cephalosporin-resistant isolates. Susceptibility data of 197,513 E. coli and 38,244 K. pneumoniae isolates were included. The proportion of extended-spectrum cephalosporin-resistant E. coli and K. pneumoniae isolates from urine and blood samples increased in all patient settings, except for K. pneumoniae isolates from patients admitted to intensive care units. For K. pneumoniae, there was a different time trend between various patient groups (p<0.01), with a significantly higher increase in extended-spectrum cephalosporin resistant isolates from patients attending a general practitioner than in isolates from hospitalized patients. For E. coli, the increasing time trends did not differ among different patient groups. This nationwide study shows a general increase in extended-spectrum cephalosporin-resistant E. coli and K. pneumoniae isolates. However, differences in trends between E. coli en K. pneumoniae underline the importance of E. coli as a community-pathogen and its subsequent influence on hospital resistance level, while for K. pneumoniae the level of resistance within the hospital seems less influenced by the resistance trends in the community. PMID- 26381749 TI - Invasive Ductal Carcinoma of the Breast in a Complex Cyst. PMID- 26381751 TI - The Invisibility of Public Health Nurses. PMID- 26381750 TI - In vitro Study of a Novel Stent Coating Using Modified CD39 Messenger RNA to Potentially Reduce Stent Angioplasty-Associated Complications. AB - BACKGROUND: Stent angioplasty provides a minimally invasive treatment for atherosclerotic vessels. However, no treatment option for atherosclerosis associated endothelial dysfunction, which is accompanied by a loss of CD39, is available, and hence, adverse effects like thromboembolism and restenosis may occur. Messenger RNA (mRNA)-based therapy represents a novel strategy, whereby de novo synthesis of a desired protein is achieved after delivery of a modified mRNA to the target cells. METHODS AND FINDINGS: Our study aimed to develop an innovative bioactive stent coating that induces overexpression of CD39 in the atherosclerotic vessel. Therefore, a modified CD39-encoding mRNA was produced by in vitro transcription. Different endothelial cells (ECs) were transfected with the mRNA, and CD39 expression and functionality were analyzed using various assays. Furthermore, CD39 mRNA was immobilized using poly(lactic-co-glycolic acid) (PLGA), and the transfection efficiency in ECs was analyzed. Our data show that ECs successfully translate in vitro-generated CD39 mRNA after transfection. The overexpressed CD39 protein is highly functional in hydrolyzing ADP and in preventing platelet activation. Furthermore, PLGA-immobilized CD39 mRNA can be delivered to ECs without losing its functionality. SUMMARY: In summary, we present a novel and promising concept for a stent coating for the treatment of atherosclerotic blood vessels, whereby patients could be protected against angioplasty-associated complications. PMID- 26381752 TI - Maternal High Fat Diet Affects Offspring's Vitamin K-Dependent Proteins Expression Levels. AB - Studies suggest bone growth & development and susceptibility to vascular disease in later life are influenced by maternal nutrition, during intrauterine and early postnatal life. There is evidence for a role of vitamin K-dependent proteins (VKDPs) including Osteocalcin, Matrix-gla protein, Periostin, and Gas6, in bone and vascular development. This study extends the analysis of VKDPs previously conducted in 6 week old offspring, into offspring of 30 weeks of age, to assess the longer term effects of a maternal and postnatal high fat (HF) diet on VKDP expression. Overall a HF maternal diet and offspring diet exacerbated the bone changes observed. Sex specific and tissue specific differences were observed in VKDP expression for both aorta and femoral tissues. In addition, significant correlations were observed between femoral OCN, Periostin Gas6, and Vkor expression levels and measures of femoral bone structure. Furthermore, MGP, OCN, Ggcx and Vkor expression levels correlated to mass and fat volume, in both sexes. In summary the current study has highlighted the importance of the long-term effects of maternal nutrition on offspring bone development and the correlation of VKDPs to bone structure. PMID- 26381753 TI - Epilepsy in adults with mitochondrial disease: A cohort study. AB - OBJECTIVE: The aim of this work was to determine the prevalence and progression of epilepsy in adult patients with mitochondrial disease. METHODS: We prospectively recruited a cohort of 182 consecutive adult patients attending a specialized mitochondrial disease clinic in Newcastle upon Tyne between January 1, 2005 and January 1, 2008. We then followed this cohort over a 7-year period, recording primary outcome measures of occurrence of first seizure, status epilepticus, stroke-like episode, and death. RESULTS: Overall prevalence of epilepsy in the cohort was 23.1%. Mean age of epilepsy onset was 29.4 years. Prevalence varied widely between genotypes, with several genotypes having no cases of epilepsy, a prevalence of 34.9% in the most common genotype (m.3243A>G mutation), and 92.3% in the m.8344A>G mutation. Among the cohort as a whole, focal seizures, with or without progression to bilateral convulsive seizures, was the most common seizure type. Conversely, all of the patients with the m.8344A>G mutation and epilepsy experienced myoclonic seizures. Patients with the m.3243A>G mutation remain at high risk of developing stroke-like episodes (1.16% per year). However, although the standardized mortality ratio for the entire cohort was high (2.86), this ratio did not differ significantly between patients with epilepsy (2.96) and those without (2.83). INTERPRETATION: Epilepsy is a common manifestation of mitochondrial disease. It develops early in the disease and, in the case of the m.3243A>G mutation, often presents in the context of a stroke like episode or status epilepticus. However, epilepsy does not itself appear to contribute to the increased mortality in mitochondrial disease. PMID- 26381754 TI - Perturbations in the Primary Metabolism of Tomato and Arabidopsis thaliana Plants Infected with the Soil-Borne Fungus Verticillium dahliae. AB - The hemibiotrophic soil-borne fungus Verticillium dahliae is a major pathogen of a number of economically important crop species. Here, the metabolic response of both tomato and Arabidopsis thaliana to V. dahliae infection was analysed by first using non-targeted GC-MS profiling. The leaf content of both major cell wall components glucuronic acid and xylose was reduced in the presence of the pathogen in tomato but enhanced in A. thaliana. The leaf content of the two tricarboxylic acid cycle intermediates fumaric acid and succinic acid was increased in the leaf of both species, reflecting a likely higher demand for reducing equivalents required for defence responses. A prominent group of affected compounds was amino acids and based on the targeted analysis in the root, it was shown that the level of 12 and four free amino acids was enhanced by the infection in, respectively, tomato and A. thaliana, with leucine and histidine being represented in both host species. The leaf content of six free amino acids was reduced in the leaf tissue of diseased A. thaliana plants, while that of two free amino acids was raised in the tomato plants. This study emphasizes the role of primary plant metabolites in adaptive responses when the fungus has colonized the plant. PMID- 26381756 TI - Risk Factors for Semilunar Valve Insufficiency After the Damus-Kaye-Stansel Procedure. AB - BACKGROUND: Cardiac function and survival after the Damus-Kaye-Stansel (DKS) procedure are encouraging, but only limited data exist related to postprocedural semilunar valve function. We investigated postprocedural midterm to long-term outcomes and changes in semilunar valve function and identified risk factors of semilunar valve function deterioration. METHODS: Between 1996 and 2012, 63 patients with a single functional ventricle underwent the DKS procedure. Of them, 50 had previously undergone pulmonary artery banding. Cardiac function was measured by catheter examination 5.3 months (interquartile range, 2.6 to 9.7) preoperatively and 1.2 years (interquartile range, 1.0 to 1.4) postoperatively. Echocardiographic examination of the semilunar valve was performed concurrently with the catheter examination and at the last follow-up (5.3 years [interquartile range, 3.1 to 9.2] postoperatively). RESULTS: The overall survival rate at 1, 5, and 10 years postoperatively was 0.97, 0.92, and 0.89, respectively. Aortic and pulmonary valve regurgitation grade 1 year postoperatively and at the last follow up increased compared with the preoperative grade. There was no significant difference between regurgitation at 1 year and the last follow-up. The duration from pulmonary artery banding to the DKS procedure was longer in the group with at least mild regurgitation (n = 6) than in the group with less than mild regurgitation (n = 54). CONCLUSIONS: Although the duration from pulmonary artery banding to the DKS procedure was associated with postoperative regurgitation, neither postprocedural aortic nor pulmonary valve regurgitation increased over time, and there were no deleterious effects on the clinical conditions. PMID- 26381755 TI - Arginine methylation of ubiquitin-associated protein 2-like is required for the accurate distribution of chromosomes. AB - Proper bioriented attachment of microtubules and kinetochores is essential for the precise distribution of duplicated chromosomes to each daughter cell. An aberrant kinetochore-microtubule attachment results in chromosome instability, which leads to cellular transformation or apoptosis. In this article, we show that ubiquitin-associated protein 2-like (UBAP2L) is necessary for correct kinetochore-microtubule attachment. Depletion of UBAP2L inhibited chromosome alignment in metaphase and delayed progression to anaphase by activating spindle assembly checkpoint signaling. In addition, UBAP2L knockdown increased side-on attachment of kinetochores along the microtubules and suppressed stable kinetochore fiber formation. A proteomics analysis identified protein arginine methyltransferase (PRMT)1 as a direct interaction partner of UBAP2L. UBAP2L has an arginine- and glycine-rich motif called the RGG/RG or GAR motif in the N terminus. Biochemical analysis confirmed that arginine residues in the RGG/RG motif of UBAP2L were directly methylated by PRMT1. Finally, we demonstrated that the RGG/RG motif of UBAP2L is essential for the proper alignment of chromosomes in metaphase for the accurate distribution of chromosomes. Our results show a possible role for arginine methylation in UBAP2L for the progression of mitosis. PMID- 26381757 TI - Refining the Nodal Staging for Esophageal Squamous Cell Carcinoma Based on Lymph Node Stations. AB - BACKGROUND: The current N category of the American Joint Committee on Cancer (AJCC) staging system for esophageal carcinoma is controversial and inapplicable for precise counting. We tested the classifiers used in the AJCC staging system and proposed a modification to this system based on the number of metastatic lymph node (LN) stations to better represent the survival characteristics of esophageal squamous cell carcinoma (ESCC) in the Chinese population. METHODS: Data from 1,351 patients with ESCC who underwent radical-intent surgical resection were reviewed. Univariate and multivariate analyses were performed to identify prognostic factors. The revised nodal categories are based on the number of metastatic LN stations. RESULTS: There was no significant difference in overall survival between patients with N2 disease and those with N3 disease (p = 0.103). Furthermore, according to the seventh edition of the AJCC staging system, no significant difference was found between stage IIIB and IIIC (p = 0.118). Based on a scatter plot, we revised the nodal classification into 4 categories: rN0 (no LN involvement), rN1 (1 station involved), rN2 (2-3 stations involved), and rN3 (>= 4 stations involved). According to the revised nodal staging system, survival could easily be distinguished between patients in rN2 and rN3 (p = 0.001) groups and also between patients with modified stage IIIB disease and modified stage IIIC disease (p = 0.007). CONCLUSIONS: The nodal categories for ESCC should be based on the number of metastatic LN stations and be classified into the following 4 groups: N0 (no LN involvement), N1 (1 station involved), N2 (2-3 stations involved), and N3 (>= 4 stations involved). PMID- 26381758 TI - Ultrasonographic and laparoscopic evaluation of the reproductive tract in older captive female cheetahs (Acinonyx jubatus). AB - The study uniquely described the clinical value of transabdominal ultrasonography for monitoring features characterizing the estrous cycle in female cheetahs (Acinonyx jubatus). The reproductive tracts of 21 female, nulliparous, and relatively aged (median: 11 and interquartile range: 9.25-14 years) captive cheetahs resident on two sites in Namibia were assessed by transabdominal ultrasound. Subsequently, the ovarian findings on ultrasound were compared with direct visualization while performing laparoscopic sterilization. A combination of these observations supported by concurrent sampling for vaginal cytology and serum progesterone concentrations defined the estrous status of individual animals. At one site, six cheetahs had been implanted with the GnRH agonist, deslorelin as a contraceptive at least once within the preceding 11 years. On ultrasound, 31 uterine horns and 35 ovaries with discernible structures on 28 (86%) were visualized in the 21 cheetahs. The uterine body was difficult to visualize because of its intrapelvic location. Eleven of 19 uteri (58%) visualized showed endometrial edema suggestive of estrogenization. The uteri of four cheetahs (19%) showed evidence of mild cystic endometrial hyperplasia. Paraovarian cysts were seen on ultrasound (n = 21) and laparoscopy (n = 26) in 16 (76.2%) and 18 (85.7%) cheetahs, respectively. Ovarian volumes obtained from ultrasonographically determined dimensions predicted cyclic activity. Laparoscopy showed that 19 ovaries had discernible follicular structures. In the study population, 10 (47.6%) cheetahs were in proestrus or estrus; none in the luteal phase; and 11 (52.4%) in anestrus. Transabdominal ultrasound, in combination with serum progesterone concentrations and vaginal cytology, was used with acceptable accuracy to assess cyclic ovarian activity in captive cheetahs. A considerable proportion of this aged population showed ovarian activity and the prevalence of paraovarian cysts was notable. A history of prior deslorelin treatment was not associated with either reproductive activity or uterine pathology. PMID- 26381759 TI - Rhythmic neural activity indicates the contribution of attention and memory to the processing of occluded movements in 10-month-old infants. AB - Infants possess the remarkable capacity to perceive occluded movements as ongoing and coherent. Little is known about the neural mechanisms that enable internal representation of conspecifics' and inanimate objects' movements during visual occlusion. In this study, 10-month-old infants watched briefly occluded human and object movements. Prior to occlusion, continuous and distorted versions of the movement were shown. EEG recordings were used to assess neural activity assumed to relate to processes of attention (occipital alpha), memory (frontal theta), and sensorimotor simulation (central alpha) before, during, and after occlusion. Oscillatory activity was analyzed using an individualized data approach taking idiosyncrasies into account. Results for occipital alpha were consistent with infants' preference for attending to social stimuli. Furthermore, frontal theta activity was more pronounced when tracking distorted as opposed to continuous movement, and when maintaining object as opposed to human movement. Central alpha did not discriminate between experimental conditions. In sum, we conclude that observing occluded movements recruits processes of attention and memory which are modulated by stimulus and movement properties. PMID- 26381760 TI - Efficacy of Steroid Pulse Therapy for Autoimmune Pancreatitis Type 1: A Retrospective Study. AB - Autoimmune pancreatitis (AIP) is treatable with steroids, but relapse is frequent. The efficacy of steroid pulse therapy has been shown for various autoimmune diseases, but has not become established therapy. In this study, we reviewed the efficacy of steroid pulse therapy in 24 subjects who were diagnosed with AIP type 1 at our hospital. Patient characteristics, time-course of serum IgG4, and the cumulative relapse-free survival rate were compared between patients who received oral steroid therapy (oral group) and those who were treated with steroid pulse therapy (pulse group). Serum IgG4 was reduced significantly after therapy in both groups and the 5-year cumulative relapse-free survival rates in the two groups did not differ significantly (oral group 46.9%, pulse group 77.8%). However, in a subset of cases with diffuse pancreatic swelling, this rate was significantly lower in the oral group (33.3% vs. 100.0%, p = 0.046). These results suggest that steroid pulse therapy is effective for prevention of relapse in AIP patients with diffuse pancreatic swelling. PMID- 26381761 TI - Three-dimensional reconstructions of solid surfaces using conventional microscopes. AB - The three-dimensional digital replicas of solid surfaces are subject of interest of different branches of science and technology. The present paper in its introductory parts brings an overview of the various microscopic reconstructive techniques based on optical sectioning. The main attention is devoted to conventional reconstruction methods and especially to that one employing the Fourier transform. The three-dimensional replicas of this special reconstructive frequency method are compared graphically and numerically with the three dimensional replicas of the confocal method. Based on the comparative study it has been concluded that the quality of the conventional replicas of surfaces possessing textures of intermediate height irregularities is acceptable and almost comparable with the quality of confocal replicas. This study is relevant both for identifying a convenient technique that provides good qualities of three dimensional replicas and for selecting the hardware whose price is affordable even for small research groups studying rougher surface textures. PMID- 26381762 TI - The Development of Fluorescent Probes for Visualizing Intracellular Hydrogen Polysulfides. AB - Endogenous hydrogen polysulfides (H2Sn; n>1) have been recognized as important regulators in sulfur-related redox biology. H2Sn can activate tumor suppressors, ion channels, and transcription factors with higher potency than H2S. Although H2Sn are drawing increasing attention, their exact mechanisms of action are still poorly understood. A major hurdle in this field is the lack of reliable and convenient methods for H2Sn detection. Herein we report a H2Sn-mediated benzodithiolone formation under mild conditions. This method takes advantage of the unique dual reactivity of H2Sn as both a nucleophile and an electrophile. Based on this reaction, three fluorescent probes (PSP-1, PSP-2, and PSP-3) were synthesized and evaluated. Among the probes prepared, PSP-3 showed a desirable off/on fluorescence response to H2Sn and high specificity. The probe was successfully applied in visualizing intracellular H2Sn. PMID- 26381763 TI - Paravalvular Regurgitation After TAVR: A Doppler Dilemma. PMID- 26381764 TI - Cardiac "Morphomics": Do We Need to Measure LV Mass and Geometry in Everyone? PMID- 26381765 TI - Native T1 Mapping for Myocardial Infarction: Time to Throw Out the Gadolinium? PMID- 26381766 TI - The Shape of LVH in Hypertension: What Does it Tell Us? PMID- 26381767 TI - FFR Derived From Coronary CT Angiography: Solving the Calcification Dilemma of Coronary CT Angiography. PMID- 26381768 TI - Morphological Characteristics of Coronary Arteries in Patients With Vasospastic Angina: Another Form of Atherosclerosis? PMID- 26381769 TI - Cardiac Imaging to Evaluate Left Ventricular Diastolic Function. AB - Left ventricular diastolic dysfunction in clinical practice is generally diagnosed by imaging. Recognition of heart failure with preserved ejection fraction has increased interest in the detection and evaluation of this condition and prompted an improved understanding of the strengths and weaknesses of different imaging modalities for evaluating diastolic dysfunction. This review briefly provides the pathophysiological background for current clinical and experimental imaging parameters of diastolic dysfunction, discusses the merits of echocardiography relative to other imaging modalities in diagnosing and grading diastolic dysfunction, summarizes lessons from clinical trials that used parameters of diastolic function as an inclusion criterion or endpoint, and indicates current areas of research. PMID- 26381771 TI - Value of 3D TEE for LAA Morphology. PMID- 26381772 TI - Comparison of Echocardiography and CT for the Assessment of Aortic Stenosis Valve Area. PMID- 26381770 TI - Noninvasive Imaging of Flow and Vascular Function in Disease of the Aorta. AB - With advancements in technology and a better understanding of human cardiovascular physiology, research as well as clinical care can go beyond dimensional anatomy offered by traditional imaging and investigate aortic functional properties and the impact disease has on this function. Linking the knowledge of the histopathological changes with the alterations in aortic function observed on noninvasive imaging results in a better understanding of disease pathophysiology. Translating this to clinical medicine, these noninvasive imaging assessments of aortic function are proving to be able to diagnose disease, better predict risk, and assess response to therapies. This review is designed to summarize the various hemodynamic measures that can characterize the aorta, the various noninvasive techniques, and applications for various disease states. PMID- 26381773 TI - Reply: Comparison of Echocardiography and CT for the Assessment of Aortic Stenosis Valve Area. PMID- 26381774 TI - Diagnosis of Coronary Disease and Icing on the Cake. PMID- 26381776 TI - Nuclear medicine and the revolution in the modern management of castration resistant prostate cancer patients: from (223)Ra-dichloride to new horizons for therapeutic response assessment. PMID- 26381775 TI - Predictive value of (18)F-FDG PET/CT in restaging patients affected by ovarian carcinoma: a multicentre study. AB - PURPOSE: Ovarian cancer is the eighth most common malignancy among women and has a high mortality rate. Prognostic factors able to drive an effective therapy are essential. (18)F-Fluoro-2-deoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) has been investigated in patients with epithelial ovarian cancer and showed promise in diagnosing, staging, detecting recurrent lesions and monitoring treatment response. Conversely, its prognostic role remains unclear. We aimed at assessing the prognostic value of (18)F-FDG PET/CT performed in the restaging process in a multicentre study. METHODS: We evaluated 168 patients affected by ovarian carcinoma, who underwent a restaging (18)F-FDG PET/CT. The presence of local recurrences, lymph node involvement and distant metastasis was recorded as well as lesion dimensions, maximum and mean standardized uptake values (SUVmax and SUVmean, respectively). Progression-free survival (PFS) and overall survival (OS) at 3 and 4 years were computed by using Kaplan-Meier curves. Increased odds ratio was assessed using Cox regression analysis testing all lesion parameters measured by PET/CT. RESULTS: PFS was significantly longer in patients with a negative than a positive restaging PET/CT study (3- and 4-year PFS 64 and 53% vs 23 and 12%, respectively; p < 0.001). Similarly, a negative study was associated with a significantly higher OS rate after 4 years of follow-up (67 vs 25% in negative and positive groups, respectively; p < 0.001). Lymph node or distant involvement were also independently associated with an increased risk of disease progression [hazard ratio (HR) 1.6 and 2.2, respectively; p = 0.003]. Moreover, PET/CT showed an incremental prognostic value compared to the International Federation of Gynecology and Obstetrics (FIGO) staging system. In the analysis of patient subsets, individuals with the same FIGO stage I-II but with negative PET had a significantly better 4-year OS than patients with low FIGO stage but positive PET. This implies that patients with the same FIGO stage can be further prognostically stratified using PET (p = 0.01). At receiver-operating characteristic (ROC) analysis, no thresholds for semiquantitative parameters were predictive of a worse outcome. CONCLUSION: (18)F-FDG PET/CT has an important prognostic value in assessing the risk of disease progression and mortality rate. An efficacious therapy planning might therefore effectively rely on (18)F-FDG PET/CT findings. Semiquantitative data were not proven to be an effective tool to predict disease progression. PMID- 26381777 TI - Genomic prediction using imputed whole-genome sequence data in Holstein Friesian cattle. AB - BACKGROUND: In contrast to currently used single nucleotide polymorphism (SNP) panels, the use of whole-genome sequence data is expected to enable the direct estimation of the effects of causal mutations on a given trait. This could lead to higher reliabilities of genomic predictions compared to those based on SNP genotypes. Also, at each generation of selection, recombination events between a SNP and a mutation can cause decay in reliability of genomic predictions based on markers rather than on the causal variants. Our objective was to investigate the use of imputed whole-genome sequence genotypes versus high-density SNP genotypes on (the persistency of) the reliability of genomic predictions using real cattle data. METHODS: Highly accurate phenotypes based on daughter performance and Illumina BovineHD Beadchip genotypes were available for 5503 Holstein Friesian bulls. The BovineHD genotypes (631,428 SNPs) of each bull were used to impute whole-genome sequence genotypes (12,590,056 SNPs) using the Beagle software. Imputation was done using a multi-breed reference panel of 429 sequenced individuals. Genomic estimated breeding values for three traits were predicted using a Bayesian stochastic search variable selection (BSSVS) model and a genome enabled best linear unbiased prediction model (GBLUP). Reliabilities of predictions were based on 2087 validation bulls, while the other 3416 bulls were used for training. RESULTS: Prediction reliabilities ranged from 0.37 to 0.52. BSSVS performed better than GBLUP in all cases. Reliabilities of genomic predictions were slightly lower with imputed sequence data than with BovineHD chip data. Also, the reliabilities tended to be lower for both sequence data and BovineHD chip data when relationships between training animals were low. No increase in persistency of prediction reliability using imputed sequence data was observed. CONCLUSIONS: Compared to BovineHD genotype data, using imputed sequence data for genomic prediction produced no advantage. To investigate the putative advantage of genomic prediction using (imputed) sequence data, a training set with a larger number of individuals that are distantly related to each other and genomic prediction models that incorporate biological information on the SNPs or that apply stricter SNP pre-selection should be considered. PMID- 26381778 TI - Does a mandibular RDP and new maxillary CD improve masticatory efficiency and quality of life in patients with a mandibular Kennedy class I arch? AB - OBJECTIVES: To evaluate the change in masticatory efficiency and quality of life of patients treated with mandibular Kennedy class I removable partial dentures (RPDs) and maxillary complete dentures at the Department of Dentistry of the Federal University of Rio Grande do Norte. MATERIALS AND METHODS: A total of 33 Kennedy class I patients were rehabilitated with maxillary complete dentures, and mandibular RPDs were selected for this non-randomized prospective intervention study. The patients had a mean age of 59.1 years. Masticatory efficiency was evaluated by colorimetric assay using fuchsin capsules. The measurements were conducted at baseline and 2 and 6 months after prosthesis insertion. Quality of life was evaluated using the Oral Health Impact Profile (OHIP-14) at baseline and 6 months after denture insertion. The Kolmogorov-Smirnov normality test was applied. Masticatory efficiency was evaluated by repeated measures ANOVA. Oral health-related quality of life was compared using the paired t test. RESULTS: There was no statistically significant difference in masticatory efficiency after denture insertion (p = 0.101). Significant differences were found (p = 0.010) for oral health-related quality of life. A significant improvement in psychological discomfort (p < 0.01) and psychological disability (p < 0.01) was observed. Mean difference value (95 % confidence interval) was 6.8 (3.8 to 9.7) points, reflecting a low impact of oral health on quality of life, considering the 0-56 range of variation of the OHIP-14 and a Cohen's d of 1.13. CONCLUSION: According to the results of the present study, rehabilitation with Kennedy class I RPDs and complete dentures did not influence masticatory efficiency but improved oral health-related quality of life. CLINICAL RELEVANCE: The association between the patient's quality of life and the masticatory efficiency is important for treatment predictability. PMID- 26381779 TI - Thermosensitive Hydrogel Co-loaded with Gold Nanoparticles and Doxorubicin for Effective Chemoradiotherapy. AB - Chemoradiotherapy, as a well-established paradigm to treat various cancers, still calls for novel strategies. Recently, gold nanoparticles (AuNPs) have been shown to play an important role as a radiosensitizer in cancer radiotherapy. The aim of this study was to evaluate the combination of polyethylene glycol (PEG) modified AuNPs and doxorubicin (DOX) to improve cancer chemoradiotherapy, in which the AuNPs was the radiosensitizer and the DOX was the model chemotherapeutic. A Pluronic(r) F127-based thermosensitive hydrogel (Au-DOX-Gel) loading AuNPs and DOX was developed by "cold method" for intratumoral injection. The formulation was optimized at a F127 concentration of 22% for Au-DOX-Gel. The release profiles compared to a control group were assessed in vitro and in vivo. Au-DOX-Gel showed sustained release of AuNPs and DOX. The cell viability and surviving fraction of mouse melanoma (B16) and Human hepatocellular liver carcinoma (HepG2) cells were significantly inhibited by the combination treatment of DOX and AuNPs under radiation. Tumor sizes of mice were significantly decreased by Au-DOX-Gel compared to controls. Interestingly, 3-(4, 5-dimethylthiazol-2-yl)-2, 5 diphenyltetrazolium bromide (MTT) assay and Ki-67 staining results showed that tumor cell growth and proliferation were inhibited by AuNPs combined with DOX under radiation, suggesting that the radiosensitization activity and combination effects might be caused by inhibition of tumor cell growth and proliferation. Furthermore, the results of skin safety tests, histological observation of organs, and the body weight changes indicated in vivo safety of Au-DOX-Gel. In conclusion, the Au-DOX-Gel developed in this study could represent a promising strategy for improved cancer chemoradiotherapy. PMID- 26381780 TI - Expression of the NLRP3 Inflammasome in Carotid Atherosclerosis. AB - BACKGROUND: The aim of the present study was to investigate NLRP3 inflammasome expression in human carotid atherosclerotic plaques and its relationship to plaque vulnerability. METHODS: Carotid atherosclerotic plaques collected from 30 patients scheduled for carotid endarterectomy (CEA) were subjected to immunohistochemical, mRNA, and protein expression studies. Ten mesenteric arteries from intestinal cancer patients served as controls for the immunohistochemical studies. Twenty individuals who had no carotid stenosis or coronary artery stenosis served as controls for analyzing atherosclerotic risk factors and for enzyme-linked immunosorbent assay (ELISA) studies. Serum samples were collected from all patients to determine interleukin-1beta (IL-1beta) and IL 18 levels. RESULTS: The NLRP3 inflammasome signaling pathway components NLRP3, ASC, caspase-1, IL-1beta, and IL-18 were strongly expressed in carotid atherosclerotic plaques, but not in healthy mesenteric arteries. Immunohistochemical, mRNA, and protein expression studies revealed higher expression levels of NLRP3, ASC, caspase-1, IL-1beta, and IL-18 in unstable compared to stable plaques. The NLRP3 inflammasome was localized in the cytoplasm of macrophages and foam cells and was associated with cholesterol crystal clefts inside and outside of cells. ELISA showed that the serum levels of the cytokines IL-1beta and IL-18 were higher in the CEA group compared to controls. CONCLUSIONS: These results demonstrated for the first time the close relationship between the expression of NLRP3 signaling pathway and human carotid atherosclerotic plaques. NLRP3, ASC, caspase-1, IL-1beta, and IL-18 were associated with plaque vulnerability and atherogenesis. The serum levels of IL 1beta and IL-18 may be useful predictors of atherosclerosis. PMID- 26381781 TI - What Do Anticoagulants Say about Microemboli? AB - BACKGROUND: In this study, we evaluated the microembolic signals (MES) frequency with transcranial Doppler ultrasound (TCD) in patients with atrial fibrillation (AF) under anticoagulant therapy, and we compared the treatment groups. METHODS: Ninety-nine patients with nonvalvular AF with a history of stroke using warfarin (46%), 67 patients using rivaroxaban (31%), and 49 patients using dabigatran (23%), that is, a total of 215 patients, who have been referred to the stroke outpatient section of our department from May 2013 to November 2014, were included in the study. CHA(2)DS(2)VASc scoring was made for all patients, and International Normalized Ratio (INR) value was evaluated in patients using warfarin. All patients were monitored with TCD on the middle cerebral arteries bilaterally for 30 minutes. Embolic signals were evaluated according to their density and the mean number of signals in 2 consecutive recordings. RESULTS: The incidence of emboli in the treatment group was 32 (32%) for warfarin, 24 (36%) for rivaroxaban, and 17 (35%) for dabigatran. The analysis of variance revealed that there was no statistically significant differences between the treatment groups in terms of patients' age (P = .145), CHA(2)DS(2)VASc scores (P = .968), and the number of emboli (P = .783). As CHA(2)DS(2)VASc score increases, number of emboli increase. A statistically significant negative correlation between the number of emboli and INR scores was found in the warfarin group. The number of emboli decreases as INR decreases. CONCLUSIONS: As we aim to reduce the risk of emboli to a minimum with anticoagulant therapy, this screening for MES can give us an idea for the risk of stroke. PMID- 26381782 TI - Toxicity of atrazine, glyphosate, and quinclorac in bullfrog tadpoles exposed to concentrations below legal limits. AB - This work sought to ascertain survival and possible changes in levels of glycogen, triglycerides, total lipids, cholesterol, protein, and lipid peroxidation in gills, liver, and muscle of bullfrog tadpoles (Lithobates catesbeianus) exposed to low concentrations of atrazine (2.5 MUg L(-1)), glyphosate (18 MUg L(-1)), and quinclorac (0.025 MUg L(-1)) at laboratorial conditions. Tadpoles showed a reduction of glycogen and triglyceride in all organs and an increase in lipid peroxidation (LPO) compared with control animals. Total lipid in gills and muscle increased in exposure to atrazine, and gills alone in exposure to glyphosate, but decreased in gills, liver, and muscle after quinclorac. Cholesterol increased in gills and liver after atrazine, in gills and muscle after glyphosate, and decreased in liver after quinclorac. Total protein in gills decreased after exposure to all herbicides, increased in muscle after atrazine, and in liver and muscle after quinclorac. These findings show that at concentrations of these herbicides tested can lead to an increase in energy expenditure to maintain homeostasis and survival of these animals despite the increase in lipid peroxidation levels in all organs analyzed. Responses observed can be one of the factors responsible for the decline in the number of amphibians around the world. PMID- 26381783 TI - Histopathological effects of silver and copper nanoparticles on the epidermis, gills, and liver of Siberian sturgeon. AB - The influence of nanoparticles (NPs) on aquatic environments is still poorly documented. The aim of the study was to determine the effects of silver (AgNPs) and copper (CuNPs) nanoparticles on larval Siberian sturgeon (Acipenser baerii) after 21 days of exposure. Acute toxicity of AgNPs on Siberian sturgeon was investigated in a 96-h static renewal study and compared with the toxicity of CuNPs. The AgNPs and CuNPs 96 h mean lethal concentrations (96 h LC50) were 15.03 +/- 2.91 and 1.41 +/- 0.24 mg L(-1), respectively. Toxicity tests were done in triplicates for each concentration of AgNPs 0.1, 0.5, 1.5 mg L(-1) and CuNPs 0.01, 0.05, 0.15 mg L(-1). The control group was exposed in freshwater. The results indicate that AgNPs and CuNPs exposure negatively influenced survival; body length and mass; and morphology and physiology of the epidermis, gills, and liver of Siberian sturgeon larvae. Fish exposed to AgNPs and CuNPs showed similar pathological changes: irregular structure and pyknotic nuclei of epidermis, aplasia and/or fusion of lamellae, telangiectasis, epithelial necrosis and lifting of the gills, dilation of sinusoidal space, overfilled blood vessels, and pyknotic nuclei of the liver. Fish exposed to CuNPs only demonstrated hyaline degeneration in the gills epithelium and liver. The study shows that CuNPs were more toxic to Siberian sturgeon larvae than AgNPs. PMID- 26381785 TI - Microbial ecology of hydrocarbon-polluted coastal sediments. PMID- 26381784 TI - Co-composting solid biowastes with alkaline materials to enhance carbon stabilization and revegetation potential. AB - Co-composting biowastes such as manures and biosolids can be used to stabilize carbon (C) without impacting the quality of these biowastes. This study investigated the effect of co-composting biowastes with alkaline materials on C stabilization and monitored the fertilization and revegetation values of these co composts. The stabilization of C in biowastes (poultry manure and biosolids) was examined by their composting in the presence of various alkaline amendments (lime, fluidized bed boiler ash, flue gas desulphurization gypsum, and red mud) for 6 months in a controlled environment. The effects of co-composting on the biowastes' properties were assessed for different physical C fractions, microbial biomass C, priming effect, potentially mineralizable nitrogen, bioavailable phosphorus, and revegetation of an urban landfill soil. Co-composting biowastes with alkaline materials increased C stabilization, attributed to interaction with alkaline materials, thereby protecting it from microbial decomposition. The co composted biowastes also increased the fertility of the landfill soil, thereby enhancing its revegetation potential. Stabilization of biowastes using alkaline materials through co-composting maintains their fertilization value in terms of improving plant growth. The co-composted biowastes also contribute to long-term soil C sequestration and reduction of bioavailability of heavy metals. PMID- 26381786 TI - Fouling characteristics and cleaning strategies of NF membranes for the advanced treatment of antibiotic production wastewater. AB - The nanofiltration (NF) membrane fouling characteristics and cleaning strategies were investigated through a laboratory-scale NF fouling test treating membrane bioreactor (MBR) effluent and MBR-granular activated carbon (GAC) effluent of an antibiotic production wastewater by DK and NF90 membranes, respectively. Results showed that organic fouling is the main NF membrane fouling for treating both the MBR effluent and MBR-GAC effluent. Soluble microbial by-product (SMP)-like and aromatic protein-like substances were the dominant components in the foulants, whereas humic-like substances had little contribution to the NF fouling. The fouling of DK was more severe than that of NF90. However, foulants respond by UV254 were more easily to foul NF90 membrane. It could get satisfactory effect using combined cleaning of acid (HCl, pH 2.0~2.5) and alkali (NaOH + 0.3 wt% NaDS, pH 10.0~10.5). The favorable cleaning strategy is "acid + alkali" for treating MBR-GAC effluent, while it is "alkali + acid" for treating MBR effluent. PMID- 26381787 TI - Forecasting PM10 in Algiers: efficacy of multilayer perceptron networks. AB - Air quality forecasting system has acquired high importance in atmospheric pollution due to its negative impacts on the environment and human health. The artificial neural network is one of the most common soft computing methods that can be pragmatic for carving such complex problem. In this paper, we used a multilayer perceptron neural network to forecast the daily averaged concentration of the respirable suspended particulates with aerodynamic diameter of not more than 10 MUm (PM10) in Algiers, Algeria. The data for training and testing the network are based on the data sampled from 2002 to 2006 collected by SAMASAFIA network center at El Hamma station. The meteorological data, air temperature, relative humidity, and wind speed, are used as inputs network parameters in the formation of model. The training patterns used correspond to 41 days data. The performance of the developed models was evaluated on the basis index of agreement and other statistical parameters. It was seen that the overall performance of model with 15 neurons is better than the ones with 5 and 10 neurons. The results of multilayer network with as few as one hidden layer and 15 neurons were quite reasonable than the ones with 5 and 10 neurons. Finally, an error around 9% has been reached. PMID- 26381788 TI - Determination of personal care products and hormones in leachate and groundwater from Polish MSW landfills by ultrasound-assisted emulsification microextraction and GC-MS. AB - Determination of the endocrine disrupting compounds (EDCs) in leachate and groundwater samples from the landfill sites is very important because of the proven harmful effects of these compounds on human and animal organisms. A method combining ultrasound-assisted emulsification microextraction (USAEME) and gas chromatography-mass spectrometry (GC-MS) was developed for simultaneous determination of seven personal care products (PCPs): methylparaben (MP), ethylparaben (EP), propylparaben (PP), buthylparaben (BP), benzophenone (BPh), 3 (4-methylbenzylidene)camphor (4-MBC), N,N-diethyltoluamide (DEET), and two hormones: estrone (E1) and beta-estradiol (E2) in landfill leachate and groundwater samples. The limit of detection (LOD)/limit of quantification (LOQ) values in landfill leachate and groundwater samples were in the range of 0.003 0.083/0.009-0.277 MUg L(-1) and 0.001-0.015/0.002-0.049 MUg L(-1), respectively. Quantitative recoveries and satisfactory precision were obtained. All studied compounds were found in the landfill leachates from Polish municipal solid waste (MSW) landfills; the concentrations were between 0.66 and 202.42 MUg L(-1). The concentration of pollutants in groundwater samples was generally below 0.1 MUg L( 1). PMID- 26381789 TI - Extracellular polymeric substances (EPS) and surface properties of activated sludges: effect of organic carbon sources. AB - The study aims to clarify how the type of organic substrate in a wastewater affects the production and composition of extracellular polymeric substances (EPS) and hydrophobicity and surface charge of activated sludges. For this purpose, three activated sludge reactors were operated in parallel with feeds composed of the organics (i) peptone, glucose, and acetate and (ii) peptone and (iii) glucose. EPS extracted from sludges were fractionated into very loosely bound, loosely bound, and tightly bound fractions and analyzed for protein and polysaccharide. Also, molecular weight distribution of proteins was determined by using high-pressure size exclusion chromatography (HPSEC). Regardless of the type of organic substrate, in each sludge, tightly bound EPS (TB-EPS) prevailed. The type of organic substrate affected the relative proportion of protein and polysaccharide and had an impact on hydrophobicity and surface charge. The sludge fed with peptone was distinctly more hydrophobic and had a lower negative surface charge than others. HPSEC fingerprints revealed that the variety and size of proteins were dependent on the type of feed. HPSEC also pointed to a shift of high molecular weight (MW) proteins from TB-EPS to others. In addition, results of a parallel study examining the inhibitory effect of Ag(+) on three sludges were interpreted along with feed composition, EPS, and surface measurements. The response of each sludge to toxic Ag(+) ion seemed to change with the type of feed. PMID- 26381790 TI - Food web of a confined and anthropogenically affected coastal basin (the Mar Piccolo of Taranto) revealed by carbon and nitrogen stable isotopes analyses. AB - Carbon and nitrogen stable isotope analysis was used to examine the food web of the Mar Piccolo of Taranto, a coastal basin experiencing several anthropogenic impacts. Main food sources (algal detritus, seaweeds, particulate organic matter (POM) and sediment organic matter (SOM)) and benthic and pelagic consumers were collected during two contrasting seasons (June and April), at four sites distributed over two inlets, and characterized by different level of confinements, anthropogenic inputs and the presence of mussels farming. delta(13)C values of organic sources revealed an important contribution of POM to both planktonic and benthic pathways, as well as the influence of terrigenous inputs within both inlets, probably due to high seasonal land runoff. Although delta(13)C of both sources and consumers varied little between sampling sites and dates, delta(15)N spatial variability was higher and clearly reflected the organic enrichment in the second inlet as well as the uptake of anthropogenically derived material by benthic consumers. On the other hand, within the first inlet, the isotopic composition of consumers did not change in response to chemical contamination. However, the impact of polluted sediments near the Navy Arsenal in the first inlet was detectable at the level of the macrobenthic trophic structure, showing high dominance of motile, upper level consumers capable to face transient conditions and the reduction of the more resident deposit feeders. We therefore underline the great potential of matching stable isotope analysis with quantitative studies of community structure to assess the effects of multiple anthropogenic stressors. PMID- 26381791 TI - Potential of barrage fish ponds for the mitigation of pesticide pollution in streams. AB - Barrage fishponds may represent a significant surface water area in some French regions. Knowledge on their effect on water resources is therefore necessary for the development of appropriate water quality management plans at the regional scale. Although there is much information on the nutrient removal capacity of these water bodies, little attention has been paid to other agricultural contaminants such as pesticides. The present paper reports the results of a 1 year field monitoring of pesticide concentrations and water flows measured upstream and downstream from a fishpond in North East France to evaluate its capacity in reducing pesticide loads. Among the 42 active substances that had been applied on the fishpond's catchment, seven pesticides (five herbicides, two fungicides) were studied. The highest concentration in the inflow to the pond was 26.5 MUg/L (MCPA), while the highest concentration in pond outflow was 0.54 MUg/L (prosulfocarb). Removal rates of dissolved pesticides in the fishpond ranged from 0-8% (prosulfocarb) to 100% (clopyralid). Although not primarily designed for the treatment of diffuse sources of pesticides, the studied fishpond had the potential to do so. PMID- 26381792 TI - Comparison of research experience and support needs of rural versus regional allied health professionals. AB - OBJECTIVE: We compared the research experience or support needs of allied health professionals in rural versus regional cities to identify if they were the same or different. DESIGN: Descriptive study using a cross sectional survey. SETTING: This study was carried within Queensland Health's northern six health services. PARTICIPANTS: Queensland health staff classified as Health Practitioners. INTERVENTIONS: This survey was conducted as part of a research capacity building initiative within Queensland Health to increase AHPs' participation in research in regional cities and rural areas of Queensland. MAIN OUTCOME MEASURES: Questions in the survey identified demographics, research experience, need for research support, research knowledge and beliefs about research. Data were compared using Chi-square and t-tests. RESULTS: The total response rate was 54.5% with 18% of the HPs located in rural communities of less than 5000 people and the rest from the three major cities in northern Queensland. Rural HPs have less research experience in most research activities than regional city HPs and need more research support. Rural HPs have more qualitative research experience than regional city HPs and research is perceived positively by both. Barriers to conducting research were similar across both groups and included insufficient time, lack of staff and no statistical support. CONCLUSION: Rural HPs are younger and have less research experience than their counterparts working in regional cities. Therefore, building rural HP research capacity initiatives may require more access to facilitators such as the Research Fellows. PMID- 26381793 TI - Inhibition of the multidrug and toxin extrusion (MATE) transporter by pyrimethamine increases the plasma concentration of metformin but does not increase antihyperglycaemic activity in humans. AB - We hypothesized that the pharmacodynamic (PD) characteristics of metformin would change with inhibition of the multidrug and toxin extrusion (MATE) transporter, which mediates renal elimination of metformin. Twenty healthy male subjects received two doses (750/500 mg) of metformin, with and without 50 mg of pyrimethamine (a potent MATE inhibitor), with 1 week of washout in between each dose. The PD characteristics of metformin were assessed using oral glucose tolerance tests (OGTTs) before and after the metformin dose. Metformin concentrations in plasma and urine were determined using liquid chromatography electrospray ionization-tandem mass spectrometry. When metformin was co administered with pyrimethamine, its area under the concentration-time curve from 0 to 12 h was 2.58-fold greater (p < 0.05), whereas the antihyperglycaemic effects of metformin were decreased. The mean differences (90% confidence interval) in mean and maximum serum glucose concentrations and in 2-h-post-OGTT serum glucose concentration were -0.6 (-1, -0.2), -0.9 (-1.6, -0.3) and -0.5 ( 1.1, 0.1) mmol/l, respectively. These findings indicate that the response to metformin is not only related to the plasma exposure of metformin but is also related to other factors, such as inhibition of uptake transporters and the gastrointestinal-based pharmacology of metformin. PMID- 26381794 TI - Variations in nitrogen use efficiency reflect the biochemical subtype while variations in water use efficiency reflect the evolutionary lineage of C4 grasses at inter-glacial CO2. AB - C4 photosynthesis evolved multiple times in diverse lineages. Most physiological studies comparing C4 plants were not conducted at the low atmospheric CO2 prevailing during their evolution. Here, 24 C4 grasses belonging to three biochemical subtypes [nicotinamide adenine dinucleotide malic enzyme (NAD-ME), phosphoenolpyruvate carboxykinase (PCK) and nicotinamide adenine dinucleotide phosphate malic enzyme (NADP-ME)] and six major evolutionary lineages were grown under ambient (400 MUL L(-1) ) and inter-glacial (280 MUL L(-1) ) CO2 . We hypothesized that nitrogen-related and water-related physiological traits are associated with subtypes and lineages, respectively. Photosynthetic rate and stomatal conductance were constrained by the shared lineage, while variation in leaf mass per area (LMA), leaf N per area, plant dry mass and plant water use efficiency were influenced by the subtype. Subtype and lineage were equally important for explaining variations in photosynthetic nitrogen use efficiency (PNUE) and photosynthetic water use efficiency (PWUE). CO2 treatment impacted most parameters. Overall, higher LMA and leaf N distinguished the Chloridoideae/NAD-ME group, while NADP-ME and PCK grasses were distinguished by higher PNUE regardless of lineage. Plants were characterized by high photosynthesis and PWUE when grown at ambient CO2 and by high conductance at inter-glacial CO2 . In conclusion, the evolutionary and biochemical diversity among C4 grasses was aligned with discernible leaf physiology, but it remains unknown whether these traits represent ecophysiological adaptation. PMID- 26381795 TI - Correlation between in vitro expansion-related cell stiffening and differentiation potential of human mesenchymal stem cells. AB - Human mesenchymal stem cells (hMSCs) are an attractive cell source for tissue regeneration, given their self-renewal and multilineage potential. However, they are present in only small percentages in human bone marrow, and are generally propagated in vitro prior to downstream use. Previous work has shown that hMSC propagation can lead to alterations in cell behavior and differentiation potency, yet optimization of differentiation based on starting cell elastic modulus is an area still under investigation. To further advance the knowledge in this field, hMSCs were cultured and routinely passaged on tissue-culture polystyrene to investigate the correlation between cell stiffening and differentiation potency during in vitro aging. Local cell elastic modulus was measured at every passage using atomic force microscopy indentation. At each passage, cells were induced to differentiate down myogenic and osteogenic paths. Cells induced to differentiate, as well as undifferentiated cells were assessed for gene and protein expression using quantitative polymerase chain reaction and immunofluorescent staining, respectively, for osteogenic and myogenic markers. Myogenic and osteogenic cell potential are highly reliant on the elastic modulus of the starting cell population (of undifferentiated cells), and this potential appears to peak when the innate cell elastic modulus is close to that of differentiated tissue. However, the latent expression of the same markers in undifferentiated cells also appears to undergo a correlative relationship with cell elastic modulus, indicating some endogenous effects of cell elastic modulus and gene/protein expression. Overall, this study correlates age-related changes with regards to innate cell stiffening and gene/protein expression in commercial hMSCs, providing some guidance as to maintenance and future use of hMSCs in future tissue engineering applications. PMID- 26381796 TI - Data analysis of diagnostic accuracies in 12-lead electrocardiogram interpretation by junior medical fellows. AB - BACKGROUND: The electrocardiogram (ECG) is the most commonly used diagnostic procedure for assessing the cardiovascular system. The aim of this study was to compare ECG diagnostic skill among fellows of cardiology and of other internal medicine specialties (non-cardiology fellows). METHODS: A total of 2900 ECG interpretations were collected. A set of 100 clinical 12-lead ECG tracings were selected and classified into 12 diagnostic categories. The ECGs were evaluated by 15 cardiology fellows and of 14 non-cardiology fellows. Diagnostic interpretations were classified as (1) correct, (2) almost correct, (3) incorrect, and (4) dangerously incorrect. Multivariate logistic regression was used to assess confounding factors and to determine the odds ratios for the months of experience, age, sex, and the distinction between cardiology and non cardiology fellows. RESULTS: The mean rate of correct diagnoses by cardiology vs. non-cardiology fellows was 48.9+/-8.9% vs. 35.9+/-8.0% (p=0.001; 70.1% vs. 55.0% for the aggregate of 'correct' and 'almost correct' diagnoses). There were 10.2+/ 5.6% of interpretations classified as 'dangerously incorrect' by cardiology fellows vs. 16.3+/-5.0% by non-cardiology fellows (p=0.008). The cardiology fellows achieved statistically significantly greater diagnostic accuracy in 7 out of the 12 diagnostic classes. In multivariable logistic regression, the distinction between cardiology and non-cardiology fellows was the only independent statistically significant (p<0.001) predictor of whether the reader is likely correct or incorrect. Being a non-cardiology fellow reduced the probability of correct classification by 42% (odds ratio [95% confidence interval]: 0.58 [0.50; 0.68]). CONCLUSIONS: Although cardiology fellows out performed the others, skills in ECG interpretation were found not adequately proficient. A comprehensive approach to ECG education is necessary. Further studies are needed to evaluate proper methods of training, testing, and continuous medical education in ECG interpretation. PMID- 26381797 TI - Development of new anatomy reconstruction software to localize cardiac isochrones to the cardiac surface from the 12 lead ECG. AB - Non-invasive electrocardiographic imaging (ECGI) of the cardiac muscle can help the pre-procedure planning of the ablation of ventricular arrhythmias by reducing the time to localize the origin. Our non-invasive ECGI system, the cardiac isochrone positioning system (CIPS), requires non-intersecting meshes of the heart, lungs and torso. However, software to reconstruct the meshes of the heart, lungs and torso with the capability to check and prevent these intersections is currently lacking. Consequently the reconstruction of a patient specific model with realistic atrial and ventricular wall thickness and incorporating blood cavities, lungs and torso usually requires additional several days of manual work. Therefore new software was developed that checks and prevents any intersections, and thus enables the use of accurate reconstructed anatomical models within CIPS. In this preliminary study we investigated the accuracy of the created patient specific anatomical models from MRI or CT. During the manual segmentation of the MRI data the boundaries of the relevant tissues are determined. The resulting contour lines are used to automatically morph reference meshes of the heart, lungs or torso to match the boundaries of the morphed tissue. Five patients were included in the study; models of the heart, lungs and torso were reconstructed from standard cardiac MRI images. The accuracy was determined by computing the distance between the segmentation contours and the morphed meshes. The average accuracy of the reconstructed cardiac geometry was within 2mm with respect to the manual segmentation contours on the MRI images. Derived wall volumes and left ventricular wall thickness were within the range reported in literature. For each reconstructed heart model the anatomical heart axis was computed using the automatically determined anatomical landmarks of the left apex and the mitral valve. The accuracy of the reconstructed heart models was well within the accuracy of the used medical image data (pixel size <1.5mm). For the lungs and torso the number of triangles in the mesh was reduced, thus decreasing the accuracy of the reconstructed mesh. A novel software tool has been introduced, which is able to reconstruct accurate cardiac anatomical models from MRI or CT within only a few hours. This new anatomical reconstruction tool might reduce the modeling errors within the cardiac isochrone positioning system and thus enable the clinical application of CIPS to localize the PVC/VT focus to the ventricular myocardium from only the standard 12 lead ECG. PMID- 26381798 TI - The derivation of the spatial QRS-T angle and the spatial ventricular gradient using the Mason-Likar 12-lead electrocardiogram. AB - Research has shown that the 'spatial QRS-T angle' (SA) and the 'spatial ventricular gradient' (SVG) have clinical value in a number of different applications. The determination of the SA and the SVG requires vectorcardiographic data. Such data is seldom recorded in clinical practice. The SA and the SVG are therefore frequently derived from 12-lead electrocardiogram (ECG) data using linear lead transformation matrices. This research compares the performance of two previously published linear lead transformation matrices (Kors and ML2VCG) in deriving the SA and the SVG from Mason-Likar (ML) 12-lead ECG data. This comparison was performed through an analysis of the estimation errors that are made when deriving the SA and the SVG for all 181 subjects in the study population. The estimation errors were quantified as the systematic error (mean difference) and the random error (span of the Bland-Altman 95% limits of agreement). The random error was found to be the dominating error component for both the Kors and the ML2VCG matrix. The random error [ML2VCG; Kors; result of the paired, two-sided Pitman-Morgan test for statistical significance of differences in the error variance between ML2VCG and Kors] for the vectorcardiographic parameters SA, magnitude of the SVG, elevation of the SVG and azimuth of the SVG were found to be [37.33 degrees ; 50.52 degrees ; p<0.001], [30.17mVms; 39.09mVms; p<0.001], [36.77 degrees ; 47.62 degrees ; p=0.001] and [63.45 degrees ; 80.32 degrees ; p<0.001] respectively. The findings of this research indicate that in comparison to the Kors matrix the ML2VCG provides greater precision for estimating the SA and SVG from ML 12-lead ECG data. PMID- 26381799 TI - P-wave pseudonormalization after iatrogenic coronary sinus isolation. AB - We report a case of a 58 year old gentleman with prior history of catheter ablation for persistent atrial fibrillation (AF). His baseline ECG showed sinus rhythm with a broad and notched P-wave in lead II and biphasic P-wave (positive/negative) in leads III and aVF previously described as advanced interatrial block. A redo ablation procedure was performed due to AF recurrence. An iatrogenic isolation of the coronary sinus (CS) was observed during ablation with marked narrowing and loss of the terminal negative component of the P-wave on the surface ECG. PMID- 26381800 TI - Discordant vs. concordant left bundle branch block: A potential clinical significance. AB - AIM: LBBB in heart failure patients has prognostic significance. Subtypes of LBBB (concordant and discordant) have not been considered when considering management. The aim of this study is to explore the clinical difference between the two subtypes. METHODS: 216 patients with LBBB were included and categorized into concordant (LBBBC) and discordant (LBBBD) groups. RESULTS: Of the 216 patients (age 69.13+/-11.7; 56% male 44% female), 133 (61.5%) were LBBBD and 83 (38.5%) were LBBBC. LBBBD patients presented with lower LVEF (mean 36% vs 51%; P<0.001), wider QRS (mean 160 ms vs 151 ms; P<0.001), larger LA (mean 45 cm(2) vs 40 cm(2); P<0.001), moderate to severe mitral and tricuspid regurgitation (17% vs 3%; P<0.05, 10% vs 1%; P<0.05 respectively), CKD (41% vs 18%; P<0.001), COPD (4.6% vs 0%; P<0.01), CAD (67% vs 36%; P<0.001), and CABG (39% vs 16%; P<0.001). CONCLUSION: LBBBD is significantly associated with worse cardiac function and clinical characteristics. PMID- 26381801 TI - [Survey on the use and behaviour of metal-metal hip replacements in Spain]. AB - BACKGROUND: Following medical device alerts published in different countries of problems with metal-on-metal total hip replacements, the Spanish Agency of Medicines and Medical Devices (AEMPS) in collaboration with the Spanish Hip Society Surgery designed a national survey to gather information on the use and behaviour of these hip implants. METHODS: The survey consisted of a questionnaire sent by e-mail to 283 clinical centre recipients of metal-on-metal hips to be filled in by surgeons with expertise in the field. RESULTS: A total of 257 questionnaires were completed. The response rate of the clinical centres was 36.7%. A total of 97.7% of the responses reported that clinical and radiological follow-ups are carried out, and 79.6% undertook metal ion analyses (chromium and cobalt). A large majority (83.6%) of the responders who had who used surface implants, and 70% of those with large-head implants reported peri-operative complications. The most common complication was pain (25% with surface implants and 30.8% with large-head implants). Currently 80.8% of those responding were considering abandoning implanting of these hip replacements. CONCLUSIONS: Despite the many limitations to this study, the survey has allowed us to obtain in a quick first view of the implant scenario of Metal on Metal hip implants in Spain, and to determine the type of patient implanted, the time of implantation, and the experience/expertise of the surgeons, and the type of follow-up carried out. PMID- 26381802 TI - Randomised clinical study: discrepancies between patient-reported outcomes and endoscopic appearance in moderate to severe ulcerative colitis. AB - BACKGROUND: Associations between patient-reported outcomes and mucosal healing have not been established in ulcerative colitis (UC). AIM: To evaluate relationships of rectal bleeding and stool frequency with mucosal healing and quality of life (QoL) in patients with UC in two Phase 3 studies (ULTRA 1 and 2). METHODS: Associations of patient-reported rectal bleeding and stool frequency subscores with mucosal healing (Mayo endoscopy subscore = 0 or 0/1) and QoL [inflammatory bowel disease questionnaire (IBDQ)] were assessed in adalimumab randomised patients (160/80 mg at Weeks 0/2 followed by 40 mg biweekly or weekly) at Weeks 8 (n = 433) and 52 (n = 299), and in patients with mucosal healing [endoscopy subscore = 0 (n = 17); 0/1 (n = 52)] at Weeks 8 and 52. RESULTS: At Week 8, the positive predictive values (PPVs) of rectal bleeding subscore = 0, stool frequency subscore = 0 or both scores = 0 for endoscopy subscore = 0/1 were 69%, 84% and 90% respectively; all proportions increased at Week 52. Equivalent PPVs for these subscores in patients with endoscopy subscore = 0 were 26%, 37% and 46% respectively. Among patients with endoscopy subscore = 0 at Week 8, 87% reported no rectal bleeding, while only 29% reported normal stool frequency; these proportions had increased to 94% and 41% respectively, at Week 52. Among patients with mucosal healing, IBDQ scores trended highest for patients with both rectal bleeding and stool frequency subscores = 0. CONCLUSIONS: Absence of rectal bleeding and normal stool frequency are often predictive of mucosal healing and QoL, but complete normalisation of stool frequency is encountered rarely in patients with mucosal healing. PMID- 26381803 TI - Risk factors for specific causes of death following pediatric heart transplant: An analysis of the registry of the International Society of Heart and Lung Transplantation. AB - We sought to determine temporal changes in COD and identify COD-specific risk factors in pediatric primary HTx recipients. Using the ISHLT registry, time dependent hazard of death after pediatric HTx, stratified by COD, was analyzed by multiphasic parametric hazard modeling with multivariable regression models for risk factor analysis. The proportion of pediatric HTx deaths from each of cardiovascular cause, allograft vasculopathy, and malignancy increased over time, while all other COD decreased post-HTx. Pre-HTx ECMO was associated with increased risk of death from graft failure (HR 2.43; p < 0.001), infection (HR 2.85; p < 0.001), and MOF (HR 2.22; p = 0.001), while post-HTx ECMO was associated with death from cerebrovascular events/bleed (HR 2.55; p = 0.001). CHD was associated with deaths due to pulmonary causes (HR 1.78; p = 0.007) or infection (HR 1.72; p < 0.001). Non-adherence was a significant risk factor for all cardiac COD, notably graft failure (HR 1.66; p = 0.001) and rejection (HR 1.89; p < 0.001). Risk factors related to specific COD are varied across different temporal phases post-HTx. Increased understanding of these factors will assist in risk stratification, guide anticipatory clinical decisions, and potentially improve patient survival. PMID- 26381804 TI - Emergency Department Expansion Versus Patient Flow Improvement: Impact on Patient Experience of Care. AB - BACKGROUND: Most strategies used to help improve the patient experience of care and ease emergency department (ED) crowding and diversion require additional space and personnel resources, major process improvement interventions, or a combination of both. OBJECTIVES: To compare the impact of ED expansion vs. patient flow improvement and the establishment of a rapid assessment unit (RAU) on the patient experience of care in a medium-size safety net ED. METHODS: This paper describes a study of a single ED wherein the department first undertook a physical expansion (2006 Q2 to 2007 Q2) followed by a reorganization of patient flow and establishment of an RAU (2009 Q2) by the use of an interrupted time series analysis. RESULTS: In the time period after ED expansion, significant negative trends were observed: decreasing Press Ganey percentiles (-4.1 percentile per quarter), increasing door-to-provider time (+4.9 minutes per quarter), increasing duration of stay (+13.2 minutes per quarter), and increasing percent of patients leaving without being seen (+0.11 per quarter). After the RAU was established, significant immediate impacts were observed for door-to-provider time (-25.8 minutes) and total duration of stay (-66.8 minutes). The trends for these indicators further suggested the improvements continued to be significant over time. Furthermore, the negative trends for the Press Ganey outcomes observed after ED expansion were significantly reversed and in the positive direction after the RAU. CONCLUSIONS: Our results demonstrate that the impact of process improvement and rapid assessment implementation is far greater than the impact of renovation and facility expansion. PMID- 26381805 TI - Structural insights on the catalytic site protection of human carbonyl reductase 1 by glutathione. AB - The NADPH-dependent human carbonyl reductase 1 (hCBR1), a member of the short chain dehydrogenase/reductase protein family, plays an important role in the ubiquitous metabolism of endogenous and xenobiotic carbonyl containing compounds. Glutathione (GSH) is also a cofactor of hCBR1, however, its role in the carbonyl reductase function of the enzyme is still unclear. In this study, we presented the crystal structure of hCBR1 in complex with GSH, in the absence of its substrates or inhibitors. Interestingly, we found that the GSH molecule presents in a configuration quite different from that was previously reported when substrate is binding to hCBR1. Our structure indicates that GSH contributes to the substrate selectivity of hCBR1 and protects the catalytic center of hCBR1 through a switch-like mechanism. The isothermal titration calorimetry and enzymology data shows that GSH directly binding with hCBR1 when there's no substrate exist. The enzymology data also shows GSH protects NADPH being attacked by oxidative small molecules. This is the first time that GSH is found to demonstrate such functions as a co-enzyme. Our crystal structure succeeds in providing critical insights into the substrate selectivity of hCBR1 and the interaction between hCBR1 and GSH. PMID- 26381806 TI - Comparison of the Fullerton Advanced Balance Scale, Mini-BESTest, and Berg Balance Scale to Predict Falls in Parkinson Disease. AB - BACKGROUND: The correct identification of patients with Parkinson disease (PD) at risk for falling is important to initiate appropriate treatment early. OBJECTIVE: This study compared the Fullerton Advanced Balance (FAB) scale with the Mini Balance Evaluation Systems Test (Mini-BESTest) and Berg Balance Scale (BBS) to identify individuals with PD at risk for falls and to analyze which of the items of the scales best predict future falls. DESIGN: This was a prospective study to assess predictive criterion-related validity. SETTING: The study was conducted at a university hospital in an urban community. PATIENTS: Eighty-five patients with idiopathic PD (Hoehn and Yahr stages: 1-4) participated in the study. MEASUREMENTS: Measures were number of falls (assessed prospectively over 6 months), FAB scale, Mini-BESTest, BBS, and Unified Parkinson's Disease Rating Scale. RESULTS: The FAB scale, Mini-BESTest, and BBS showed similar accuracy to predict future falls, with values for area under the curve (AUC) of the receiver operating characteristic (ROC) curve of 0.68, 0.65, and 0.69, respectively. A model combining the items "tandem stance," "rise to toes," "one-leg stance," "compensatory stepping backward," "turning," and "placing alternate foot on stool" had an AUC of 0.84 of the ROC curve. LIMITATIONS: There was a dropout rate of 19/85 participants. CONCLUSIONS: The FAB scale, Mini-BESTest, and BBS provide moderate capacity to predict "fallers" (people with one or more falls) from "nonfallers." Only some items of the 3 scales contribute to the detection of future falls. Clinicians should particularly focus on the item "tandem stance" along with the items "one-leg stance," "rise to toes," "compensatory stepping backward," "turning 360 degrees ," and "placing foot on stool" when analyzing postural control deficits related to fall risk. Future research should analyze whether balance training including the aforementioned items is effective in reducing fall risk. PMID- 26381807 TI - Implementation of a Quality Improvement Process Aimed to Deliver Higher-Value Physical Therapy for Patients With Low Back Pain: Case Report. AB - BACKGROUND AND PURPOSE: The current state of health care demands higher-value care. Due to many barriers, clinicians routinely do not implement evidence-based care even though it is known to improve quality and reduce cost of care. The purpose of this case report is to describe a theory-based, multitactic implementation of a quality improvement process aimed to deliver higher-value physical therapy for patients with low back pain. CASE DESCRIPTION: Patients were treated from January 2010 through December 2014 in 1 of 32 outpatient physical therapy clinics within an academic health care system. Data were examined from 47,755 patients (mean age=50.3 years) entering outpatient physical therapy for management of nonspecific low back pain, with or without radicular pain. Development and implementation tactics were constructed from adult learning and change management theory to enhance adherence to best practice care among 130 physical therapists. A quality improvement team implemented 4 tactics: establish care delivery expectations, facilitate peer-led clinical and operational teams, foster a learning environment focused on meeting a population's needs, and continuously collect and analyze outcomes data. Physical therapy utilization and change in functional disability were measured to assess relative cost and quality of care. Secondarily, charge data assessed change in physical therapists' application of evidence-based care. OUTCOMES: Implementation of a quality improvement process was measured by year-over-year improved clinical outcomes, decreased utilization, and increased adherence to evidence-based physical therapy, which was associated with higher-value care. DISCUSSION: When adult learning and change management theory are combined in quality improvement efforts, common barriers to implementing evidence-based care can be overcome, creating an environment supportive of delivering higher-value physical therapy for patients with low back pain. PMID- 26381809 TI - Aligning Documentation With Congenital Muscular Torticollis Clinical Practice Guidelines: Administrative Case Report. AB - BACKGROUND AND PURPOSE: A hospital-based pediatric outpatient center, wanting to weave evidence into practice, initiated an update of knowledge, skills, and documentation patterns with its staff physical therapists and occupational therapists who treat people with congenital muscular torticollis (CMT). This case report describes 2 cycles of implementation: (1) the facilitators and barriers to implementation and (2) selected quality improvement outcomes aligned with published clinical practice guidelines (CPGs). CASE DESCRIPTION: The Pediatric Therapy Services of St Joseph's Regional Medical Center in New Jersey has 4 full time, 1 part-time, and 3 per diem staff. Chart audits in 2012 revealed variations in measurement, interventions, and documentation that led to quality improvement initiatives. An iterative process, loosely following the knowledge-to-action cycle, included a series of in-service training sessions to review the basic anatomy, pathokinesiology, and treatment strategies for CMT; reading assignments of the available CPGs; journal review; documentation revisions; and training on the recommended measurements to implement 2 published CPGs and measure outcomes. OUTCOMES: A previous 1-page generic narrative became a 3-page CMT-specific form aligned with the American Physical Therapy Association Section on Pediatrics CMT CPG recommendations. Staff training on the Face, Legs, Activity, Cry, Consolability (FLACC) pain scale, classification of severity, type of CMT, prognostication, measures of cervical range of motion, and developmental progression improved documentation consistency from 0% to 81.9% to 100%. Clinicians responded positively to using the longer initial evaluation form. DISCUSSION: Successful implementation of both clinical and documentation practices were facilitated by a multifaceted approach to knowledge translation that included a culture supportive of evidence-based practice, administrative support for training and documentation redesign, commitment by clinicians to embrace changes aimed at improved care, and clinical guidelines that provide implementable recommendations. PMID- 26381808 TI - Cognitive Contributions to Freezing of Gait in Parkinson Disease: Implications for Physical Rehabilitation. AB - People with Parkinson disease (PD) who show freezing of gait also have dysfunction in cognitive domains that interact with mobility. Specifically, freezing of gait is associated with executive dysfunction involving response inhibition, divided attention or switching attention, and visuospatial function. The neural control impairments leading to freezing of gait have recently been attributed to higher-level, executive and attentional cortical processes involved in coordinating posture and gait rather than to lower-level, sensorimotor impairments. To date, rehabilitation for freezing of gait primarily has focused on compensatory mobility training to overcome freezing events, such as sensory cueing and voluntary step planning. Recently, a few interventions have focused on restitutive, rather than compensatory, therapy. Given the documented impairments in executive function specific to patients with PD who freeze and increasing evidence of overlap between cognitive and motor function, incorporating cognitive challenges with mobility training may have important benefits for patients with freezing of gait. Thus, a novel theoretical framework is proposed for exercise interventions that jointly address both the specific cognitive and mobility challenges of people with PD who freeze. PMID- 26381810 TI - BDNF Val66Met Polymorphism Is Related to Motor System Function After Stroke. AB - BACKGROUND: The val(66)met polymorphism in brain-derived neurotrophic factor (BDNF) has been associated with poorer outcomes after stroke. The mechanism for this finding remains uncertain but might be related to the reduced motor system activation associated with this polymorphism in healthy people. OBJECTIVE: The current study examined whether the presence of the BDNF val(66)met polymorphism is associated with reduced motor system activation after stroke. DESIGN AND METHODS: Forty-two patients with stroke who were enrolled in 1 of 2 studies of robot-assisted arm motor therapy participated in the study. All participants were tested for the BDNF val(66)met polymorphism followed by functional magnetic resonance imaging during affected hand movement. RESULTS: Participants averaged 12 months poststroke and had wide-ranging motor deficits (Fugl-Meyer scale scores=14-60). Brain activation in participants without the BDNF val(66)met polymorphism (n=26) spanned bilateral motor networks with a larger volume (total=334 cc) than that found in participants with this polymorphism (n=16) (97 cc). Regional analyses were consistent. Participants without this polymorphism showed larger ipsilesional primary sensorimotor cortex activation volume and magnitude compared with those in whom the polymorphism was present. LIMITATIONS: The extent to which these findings generalize to other populations of people with stroke, such as those with stroke <7 days prior, remains uncertain. CONCLUSIONS: Functional magnetic resonance imaging during affected hand movement showed decreased brain activation among participants with the BDNF val(66)met polymorphism compared with those lacking this polymorphism, especially in the ipsilesional primary sensorimotor cortex contralateral to movement. These results echo findings in healthy people and suggest that genetic factors affecting the normal brain continue to be operative after stroke. The findings suggest a potential imaging-based endophenotype for the BDNF val(66)met polymorphism's effect on the motor system that may be useful in a clinical trial setting. PMID- 26381811 TI - Modafinil for cognitive neuroenhancement in healthy non-sleep-deprived subjects: A systematic review. AB - Modafinil is an FDA-approved eugeroic that directly increases cortical catecholamine levels, indirectly upregulates cerebral serotonin, glutamate, orexin, and histamine levels, and indirectly decreases cerebral gamma-amino butrytic acid levels. In addition to its approved use treating excessive somnolence, modafinil is thought to be used widely off-prescription for cognitive enhancement. However, despite this popularity, there has been little consensus on the extent and nature of the cognitive effects of modafinil in healthy, non-sleep deprived humans. This problem is compounded by methodological discrepancies within the literature, and reliance on psychometric tests designed to detect cognitive effects in ill rather than healthy populations. In order to provide an up-to-date systematic evaluation that addresses these concerns, we searched MEDLINE with the terms "modafinil" and "cognitive", and reviewed all resultant primary studies in English from January 1990 until December 2014 investigating the cognitive actions of modafinil in healthy non-sleep-deprived humans. We found that whilst most studies employing basic testing paradigms show that modafinil intake enhances executive function, only half show improvements in attention and learning and memory, and a few even report impairments in divergent creative thinking. In contrast, when more complex assessments are used, modafinil appears to consistently engender enhancement of attention, executive functions, and learning. Importantly, we did not observe any preponderances for side effects or mood changes. Finally, in light of the methodological discrepancies encountered within this literature, we conclude with a series of recommendations on how to optimally detect valid, robust, and consistent effects in healthy populations that should aid future assessment of neuroenhancement. PMID- 26381812 TI - Leucettine L41, a DYRK1A-preferential DYRKs/CLKs inhibitor, prevents memory impairments and neurotoxicity induced by oligomeric Abeta25-35 peptide administration in mice. AB - Dual-specificity tyrosine phosphorylation-regulated kinases (DYRKs) and cdc2-like kinases (CLKs) are implicated in the onset and progression of Down syndrome (DS) and Alzheimer's disease (AD). DYRK1A has emerged as a possible link between amyloid-beta (Abeta) and Tau, the major pathological proteins in AD. We here assessed the neuroprotective potential of a novel inhibitor of DYRKs/CLKs. The Leucettine L41, acting preferentially on DYRK1A, was tested in Abeta25-35-treated mice, a nontransgenic model of AD-like toxicity. We co-injected intracerebroventricularly oligomeric Abeta25-35 peptide and L41 in Swiss male mice. After 7 days, they were submitted to behavioral tests addressing spatial and non-spatial, short- and long-term memories. The oxidative stress, apoptotic markers, kinases involved in Tau phosphorylation, and synaptic integrity were analyzed by Western blot and ELISA in the hippocampus. L41, tested at 0.4, 1.2, 4 ug, prevented the Abeta25-35-induced memory deficits in the Y-maze, passive avoidance and water-maze tests, with the most active dose being 4 ug. The inhibitor prevented the Abeta25-35-induced oxidative stress, as revealed by measures of lipid peroxidation levels and reactive oxygen species accumulation, and abolished Abeta25-35-induced expression of pro-apoptotic markers. L41 prevented the Abeta25-35-induced decrease of AKT activation and increase of glycogen synthase kinase-3beta (GSK-3beta) activation, resulting in a decrease of Tau phosphorylation. Finally, L41 restored Abeta25-35-reduced levels of synaptic markers. The novel DYRK1A-preferential inhibitor L41 therefore prevented Abeta25 35-induced memory impairments and neurotoxicity in the mouse hippocampus. These in vivo data highlighted particularly DYRK1A as a major kinase involved in Abeta pathology and suggested therapeutic developments for DYRK1A inhibitors in AD. PMID- 26381813 TI - Multi-Fluorinated Azido Coumarins for Rapid and Selective Detection of Biological H2 S in Living Cells. AB - Hydrogen sulfide (H2 S) is an endogenously produced gaseous signaling molecule with multiple biological functions. In order to visualize the endogenous in situ production of H2 S in living cells in real time, here we developed multi fluorinated azido coumarins as fluorescent probes for the rapid and selective detection of biological H2 S. Kinetic studies indicated that an increase in fluorine substitution leads to an increased rate of H2 S-mediated reduction reaction, which is also supported by our theoretical calculations. To our delight, tetra-fluorinated coumarin 1 could react with H2 S fast (t1/2 ~1 min) and selectively, which could be further used for continuous enzymatic assays and for visualization of intracellular H2 S. Bioimaging results obtained with 1 revealed that d-Cys could induce a higher level of endogenous H2 S production than l-Cys in a time-dependent manner in living cell. PMID- 26381814 TI - Medical Students' Stress, Psychological Morbidity, and Coping Strategies: a Cross Sectional Study from Pakistan. AB - OBJECTIVE: The authors studied the prevalence of psychological morbidity, sources and severity of stresses, as well as coping strategies in Pakistani medical students. METHODS: Medical students in Lahore, Pakistan, completed a cross sectional, self-administered questionnaire in 2013 on the sources and severity of various stressors. The General Health Questionnaire-12 (GHQ-12) and Brief COPE assessed the psychological morbidity and coping strategies. RESULTS: Out of 1500 students, 527 responded to the survey. The prevalence of psychological morbidity was 23.3%; 52.3% respondents showed evidence of distress. By logistic regression analysis, GHQ-12 caseness was associated with being male and occurrence of health related stressors. The most common stressors were related to academic concerns. Coping strategies showed variation by GHQ-caseness. CONCLUSION: The significant psychological morbidity and distress warrants establishing support systems to support students and bringing about evidence-based changes to teaching and evaluation systems. Adequate counseling facilities should be made available and students encouraged to seek help. PMID- 26381816 TI - Provable quantum advantage in randomness processing. AB - Quantum advantage is notoriously hard to find and even harder to prove. For example the class of functions computable with classical physics exactly coincides with the class computable quantum mechanically. It is strongly believed, but not proven, that quantum computing provides exponential speed-up for a range of problems, such as factoring. Here we address a computational scenario of randomness processing in which quantum theory provably yields, not only resource reduction over classical stochastic physics, but a strictly larger class of problems which can be solved. Beyond new foundational insights into the nature and malleability of randomness, and the distinction between quantum and classical information, these results also offer the potential of developing classically intractable simulations with currently accessible quantum technologies. PMID- 26381815 TI - Sensitive western blotting for detection of endogenous Ser129-phosphorylated alpha-synuclein in intracellular and extracellular spaces. AB - alpha-Synuclein deposited in Lewy bodies, a pathological hallmark of Parkinson's disease (PD), is highly phosphorylated at serine 129 (Ser129). In contrast, there is very little Ser129-phosphorylated alpha-synuclein in the normal brains. This difference suggests that Ser129-phosphorylation is involved in neurodegenerative processes of PD. However, the role of this modification remains unclear. One limiting factor for relevant biochemical analyses is that it is difficult to detect endogenous Ser129-phosphorylated alpha-synuclein by western blotting, because alpha-synuclein monomers detached from the transferred membrane during incubation. Here, we reported that combination fixation of the transferred membrane with 4% paraformaldehyde and 0.01 ~ 0.1% glutaraldehyde produced an approximately 10-fold increase in the sensitivity for Ser129-phosphorylated alpha synuclein monomers, allowing detection of endogenous proteins even in conditioned medium, human cerebrospinal fluid, and extracts from cell lines and human brain. This method may enable more detailed biochemical analyses for alpha-synuclein transmission between intra and extracellular spaces under physiological and pathological conditions. PMID- 26381817 TI - SeqMule: automated pipeline for analysis of human exome/genome sequencing data. AB - Next-generation sequencing (NGS) technology has greatly helped us identify disease-contributory variants for Mendelian diseases. However, users are often faced with issues such as software compatibility, complicated configuration, and no access to high-performance computing facility. Discrepancies exist among aligners and variant callers. We developed a computational pipeline, SeqMule, to perform automated variant calling from NGS data on human genomes and exomes. SeqMule integrates computational-cluster-free parallelization capability built on top of the variant callers, and facilitates normalization/intersection of variant calls to generate consensus set with high confidence. SeqMule integrates 5 alignment tools, 5 variant calling algorithms and accepts various combinations all by one-line command, therefore allowing highly flexible yet fully automated variant calling. In a modern machine (2 Intel Xeon X5650 CPUs, 48 GB memory), when fast turn-around is needed, SeqMule generates annotated VCF files in a day from a 30X whole-genome sequencing data set; when more accurate calling is needed, SeqMule generates consensus call set that improves over single callers, as measured by both Mendelian error rate and consistency. SeqMule supports Sun Grid Engine for parallel processing, offers turn-key solution for deployment on Amazon Web Services, allows quality check, Mendelian error check, consistency evaluation, HTML-based reports. SeqMule is available at http://seqmule.openbioinformatics.org. PMID- 26381818 TI - Transjugular Intrahepatic Portosystemic Shunt for Extrahepatic Portal Venous Obstruction in Children. AB - OBJECTIVES: To evaluate the feasibility and efficacy of transjugular intrahepatic portosystemic shunt (TIPS) for extrahepatic portal venous obstruction with recurrent variceal bleeding in children. METHODS: From November 2005 to December 2013, 28 consecutive paediatric patients with extrahepatic portal venous obstruction treated with TIPS for recurrent variceal bleeding refractory to medical/endoscopic therapy and/or surgical treatment in a tertiary-care centre were followed until last clinical evaluation or death. The median follow-up time was 36.0 months (range 4.0-106.0 months). RESULTS: Seventeen boys and 11 girls of ages 7.1 to 17.9 years (median 12.3 years) weighing 19.0 to 62.0 kg (median 33.5 kg) were treated. TIPS was successfully placed in 17 of 28 (60.7%) patients via a transjugular approach alone (n = 4), a combined transjugular/transhepatic approach (n = 9), or a combined transjugular/transsplenic approach (n = 4). Shunt dysfunction occurred in 6 of 17 (35.3%) patients. The cumulative 1- and 3-year free-from-variceal-rebleeding rates in TIPS success group were higher than those in TIPS failure group (75.0% and 67.5% vs 45.5% and 18.2%, respectively, P = 0.0075). Compared with the TIPS failure group, the improvements in the height-for age z scores were greater in the TIPS success group (P = 0.017). Procedure related complication occurred in 1 patient (3.6%), and no episode of post-TIPS hepatic encephalopathy occurred in any patient. Except 1 patient in the TIPS success group died at 115 postoperative days, all patients were alive. CONCLUSIONS: TIPS is feasible and effective in children with extrahepatic portal venous obstruction and recurrent variceal bleeding. TIPS could represent a less invasive alternative to traditional surgical portosystemic shunting or a valuable treatment option if surgery and endoscopic treatment failed. PMID- 26381819 TI - Early Screening in Children at Genetic Risk of Coeliac Disease. PMID- 26381820 TI - Reply: Strategy and suppression impairments after right lateral and orbito frontal lesions. PMID- 26381821 TI - Strategy and suppression impairments after right lateral prefrontal and orbito frontal lesions. PMID- 26381824 TI - Quantum dynamics of the photostability of pyrazine. AB - We investigate the radiationless decay of photoexcited pyrazine to its ground electronic state using multireference electronic structure and quantum dynamics calculations. We construct a quadratic vibronic coupling Hamiltonian, including the four lowest electronic states and ten vibrational modes, by fitting to more than 5000 ab initio points. We then use this model to simulate the non-adiabatic excited state dynamics of the molecule using the multi-configuration time dependent Hartree method. On the basis of these calculations, we propose a new mechanism for this decay process involving a conical intersection between the Au(npi*) state and the ground state. After excitation to the B2u(pipi*) state, the molecule decays to both the B3u(npi*) and Au(npi*) states on an ultrashort timescale of approximately 20 fs. The radiationless decay to the ground state then occurs from the Au(npi*) state on a much longer timescale. PMID- 26381822 TI - Role of Src in Vascular Hyperpermeability Induced by Advanced Glycation End Products. AB - The disruption of microvascular barrier in response to advanced glycation end products (AGEs) stimulation contributes to vasculopathy associated with diabetes mellitus. Here, to study the role of Src and its association with moesin, VE cadherin and focal adhesion kinase (FAK) in AGE-induced vascular hyperpermeability, we verified that AGE induced phosphorylation of Src, causing increased permeability in HUVECs. Cells over-expressed Src displayed a higher permeability after AGE treatment, accompanied with more obvious F-actin rearrangement. Activation of Src with pcDNA3/flag-Src(Y530F) alone duplicated these effects. Inhibition of Src with siRNA, PP2 or pcDNA3/flag-Src(K298M) abolished these effects. The pulmonary microvascular endothelial cells (PMVECs) isolated from receptor for AGEs (RAGE)-knockout mice decreased the phosphorylation of Src and attenuated the barrier dysfunction after AGE treatment. In vivo study showed that the exudation of dextran from mesenteric venules was increased in AGE-treated mouse. This was attenuated in RAGE knockout or PP2-pretreated mice. Up-regulation of Src activity induced the phosphorylation of moesin, as well as activation and dissociation of VE-cadherin, while down regulation of Src abolished these effects. FAK was also proved to interact with Src in HUVECs stimulated with AGEs. Our studies demonstrated that Src plays a critical role in AGE-induced microvascular hyperpermeability by phosphorylating moesin, VE-cadherin, and FAK respectively. PMID- 26381823 TI - A role for the transducer of the Hippo pathway, TAZ, in the development of aggressive types of endometrial cancer. AB - Although TAZ, the final effector of the Hippo pathway that modulates epithelial to mesenchymal transition and stemness, has been implicated in the development of different types of cancer, its role in endometrial cancer has not yet been studied. Thus, we evaluated the expression of TAZ in different types of endometrial cancer by immunohistochemistry. TAZ expression was detected in 76% of undifferentiated endometrial carcinomas, 54% of endometrial carcinosarcomas, 46% of endometrial serous carcinomas, 36% of grade 3 endometrioid carcinomas, and 18% of grade 1-2 endometrioid carcinomas, with statistically significant differences. We analyzed the WWTR1 gene that encodes TAZ by FISH and MassARRAY spectrometry, ruling out gene amplification and differential promoter methylation as the main mechanisms that modulate TAZ expression in endometrial tumors. However, we did detect a significant association between Scribble hypoexpression and delocalization with TAZ expression. Moreover, we demonstrated that TAZ promoted invasiveness, and it favored cell motility and tumor growth, in endometrial cancer cell lines. In addition, TAZ expression was associated with the transition from an epithelial to mesenchymal phenotype, both in vitro and in human tumors. Together, these data reveal a previously unknown role for TAZ and the Hippo pathway in the progression of aggressive subtypes of endometrial cancer. PMID- 26381825 TI - Charge transfer between carbon nanotubes on surfaces. AB - The charge transfer between neighboring single-walled carbon nanotubes (SWNTs) on a silicon oxide surface was investigated as a function of both the SWNT nature (metallic or semiconducting) and the anode/cathode distance using scanning probe techniques. Two main mechanisms were observed: a direct electron tunneling described by the typical Fowler-Nordheim model, and indirect electron transfer (hopping) mediated by functional groups on the supporting surface. Both mechanisms depend on the SWNT nature and on the anode/cathode separation: direct electron tunneling dominates the charge transfer process for metallic SWNTs, especially for large distances, while both mechanisms compete with each other for semiconducting SWNTs, prevailing one over the other depending on the anode/cathode separation. These mechanisms may significantly influence the design and operation of SWNT-based electronic devices. PMID- 26381827 TI - Trialkyl Methanetricarboxylate as Dialkyl Malonate Surrogate in Copper-Catalyzed Enantioselective Propargylic Substitution. AB - The first copper-catalyzed enantioselective propargylation of trialkyl methantricarboxylate with propargylic alcohol derivatives was developed. The tricarboxylate unit in the obtained adducts could be easily transformed into a malonate moiety by treating with in situ generated NaOEt in excellent yield without racemization. PMID- 26381826 TI - A Simplified System for Evaluating Cell Mechanosensing and Durotaxis In Vitro. AB - The composition and mechanical properties of the extracellular matrix are highly variable between tissue types. This connective tissue stroma diversity greatly impacts cell behavior to regulate normal and pathologic processes including cell proliferation, differentiation, adhesion signaling and directional migration. In this regard, the innate ability of certain cell types to migrate towards a stiffer, or less compliant matrix substrate is referred to as durotaxis. This phenomenon plays an important role during embryonic development, wound repair and cancer cell invasion. Here, we describe a straightforward assay to study durotaxis, in vitro, using polydimethylsiloxane (PDMS) substrates. Preparation of the described durotaxis chambers creates a rigidity interface between the relatively soft PDMS gel and a rigid glass coverslip. In the example provided, we have used these durotaxis chambers to demonstrate a role for the cdc42/Rac1 GTPase activating protein, cdGAP, in mechanosensing and durotaxis regulation in human U2OS osteosarcoma cells. This assay is readily adaptable to other cell types and/or knockdown of other proteins of interests to explore their respective roles in mechanosignaling and durotaxis. PMID- 26381828 TI - Why does high pressure destroy co-non-solvency of PNIPAm in aqueous methanol? AB - It is well known that poly(N-isopropylacrylamide) (PNIPAm) exhibits an interesting, yet puzzling, phenomenon of co-non-solvency. Co-non-solvency occurs when two competing good solvents for PNIPAm, such as water and alcohol, are mixed together. As a result, the same PNIPAm collapses within intermediate mixing ratios. This complex conformational transition is driven by preferential binding of methanol with PNIPAm. Interestingly, co-non-solvency can be destroyed when applying high hydrostatic pressures. In this work, using a large scale molecular dynamics simulation employing high pressures, we propose a microscopic picture behind the suppression of the co-non-solvency phenomenon. Based on thermodynamic and structural analysis, our results suggest that the preferential binding of methanol with PNIPAm gets partially lost at high pressures, making the background fluid reasonably homogeneous for the polymer. This is consistent with the hypothesis that the co-non-solvency phenomenon is driven by preferential binding and is not based on depletion effects. PMID- 26381830 TI - Leaders in Nursing Informatics Education and Research: The University of Utah Celebrates 25 Years. PMID- 26381832 TI - Mouse model of experimental Eustachian tube occlusion: a surgical technique. AB - CONCLUSION: The present study demonstrates a mouse model of chronic Eustachian tube (ET) dysfunction using a surgical technique that is reproducible and effective with low mortality and morbidity. OBJECTIVE: To create a reproducible and effective mouse model of ET obstruction with a low operative morbidity. METHODS: Forty healthy, male CBA/CaJ mice underwent the procedure. ET obstruction was performed on one side under general anesthesia; A small piece of dental material (Gutta Percha Points, Meta Biomed, Chungbuk, Korea) was placed via the tympanic orifice of the ET to occlude the entire ET. The contralateral ears of animals served as a control. One month after the operation, all ears were inspected under an operating microscope for signs of ET dysfunction. Primary outcome measures were the signs of ET dysfunction inspected through tympanic membrane (TM) 4 weeks after the operation and confirmation of ET occlusion by post-mortem dissection. RESULTS: Forty (100%) of the treated mice ears developed ET dysfunction, as confirmed by the middle ear appearance on otoscopy and dissection post-mortem and 0% of the control ears at 4 weeks. The most common otoscopic signs were thickened TMs and middle ear effusions. No mortality or morbidity occurred either from anesthesia or surgery. PMID- 26381833 TI - Enhancement of motion perception in the direction opposite to smooth pursuit eye movement. AB - When eyes track a moving target, a stationary background environment moves in the direction opposite to the eye movement on the observer's retina. Here, we report a novel effect in which smooth pursuit can enhance the retinal motion in the direction opposite to eye movement, under certain conditions. While performing smooth pursuit, the observers were presented with a counterphase grating on the retina. The counterphase grating consisted of two drifting component gratings: one drifting in the direction opposite to the eye movement and the other drifting in the same direction as the pursuit. Although the overall perceived motion direction should be ambiguous if only retinal information is considered, our results indicated that the stimulus almost always appeared to be moving in the direction opposite to the pursuit direction. This effect was ascribable to the perceptual dominance of the environmentally stationary component over the other. The effect was robust at suprathreshold contrasts, but it disappeared at lower overall contrasts. The effect was not associated with motion capture by a reference frame served by peripheral moving images. Our findings also indicate that the brain exploits eye-movement information not only for eye-contingent image motion suppression but also to develop an ecologically plausible interpretation of ambiguous retinal motion signals. Based on this biological assumption, we argue that visual processing has the functional consequence of reducing the apparent motion blur of a stationary background pattern during eye movements and that it does so through integration of the trajectories of pattern and color signals.